PMID- 16402514
TI  - Cystic endometrial hyperplasia-pyometra complex in cats. A review.
AB  - Presentation of complex cystic endometrial hyperplasia-pyometra is not very
      common in cats. As in bitches, hormonal influences result in environmental and
      histological changes in the uterus leading to predisposition to bacterial growth.
      Its influence on the organism provokes certain clinical signs. Diagnosis and
      treatment must be fast and aggressive. Depending on the clinical status and queen
      purpose, it can be both surgical or medical. Both of them offer a high rate of
      success if the detailed protocols are followed.

PMID- 16402515
TI  - Analysis of the 96 most often cited articles published in veterinary journals in
      2002 and 2003.
AB  - The study concerned 123 Journals of the category "Veterinary Sciences" as defined
      in the Journal Citation Reports (Institute for Scientific Information (ISI),
      Philadelphia, USA). Using Web of Knowledge (ISI, USA), update December 3, 2005,
      articles published in 2002 and 2003 and cited 20 times or more were selected. The
      total number of selected articles was 96. They were published in 34 out of the
      123 journals. Based on the country of the first author, the articles originated
      form 24 countries. Forty-nine of the 96 articles (51%) were written in only two
      countries being England (15) and the USA (34). The articles could be classified
      in six categories being immunology (21), microbiology and directly related
      subjects (48), prions and prion-induced diseases (5), reproduction (23),
      toxicology (3), and miscellanea (11). The category "microbiology" (48) was
      divided into six subcategories: general (1), bacteriology (17), mycology (3),
      parasitology (5), protozoology (6), and virology (5). Some articles were
      classified in more than one (sub)category.

PMID- 16402516
TI  - [Chronic lead intoxication associated with Ayurvedic medication].
AB  - A 46-year-old man with multiple sclerosis had severe generalised pain for which
      treatment with paracetamol, ibuprofen, gabapentin and methyl-prednisolone had
      been unsuccessful. In addition normocytic anaemia without haemolysis and with a
      normal iron load was found. Due to bright red rectal blood loss and nausea,
      vomiting, weight loss, anorexia, abdominal pain and constipation a colonoscopy
      was planned. However, before this was performed, manual slide differentiation of
      a blood smear showed basophilic stippling and it turned out that the patient had
      been taking Ayurvedic medication up to one month before presentation. A
      moderately severe lead intoxication was diagnosed: 0.77 mg/l. The herbal
      medication had a very high lead content. The patient was successfully treated
      with the oral lead chelator 23-dimercaptosuccinic acid. Traditional and folk
      remedies often are important causes of lead poisoning.

PMID- 16402517
TI  - [Probabilities cannot be calculated retrospectively--not even in the courtroom].
AB  - Chance events are part of everyday life, but coincidence of diseases often raises
      suspicions about hidden causes, for example when power lines are blamed for the
      geographical clustering of cancer. Recently, criminal procedures in the
      Netherlands have revolved around the question of whether statistical
      'predictions' are a valid reason to hold a hospital nurse accountable for the
      occurrence of excess deaths during her duty hours, or a kindergarten employee for
      unexplained respiratory problems in several infants. In both cases, the appeals
      court judges did not accept the statistical 'argument' in the absence of other
      evidence. In the UK, however, Sally Clark's initial life sentence for the double
      murder of her 2 babies was largely based on 'probabilities in retrospect', put
      forward by the paediatrician Sir Roy Meadow as an expert witness. 4 years later
      she was acquitted, whereas Meadow was struck off the medical register on a charge
      of professional misconduct. There is no Bayesian or other mathematical solution
      to the problem of chance events. Only the detection of causal factors that are
      plausible and supported by new evidence can help to reinterpret coincidences as
      relationships. Scrupulous reasoning about probabilities is required, not only of
      physicians but also of judges and politicians.

PMID- 16402518
TI  - [Use of stairs in a hospital increased by a sign near the stairs or the
      elevator].
AB  - OBJECTIVE: To investigate whether signs encouraging taking the stairs or
      discouraging taking the elevator lead to an increasing number of patients taking
      the stairs instead of the elevator in a hospital. DESIGN: Interventional study.
      METHOD: During a period of 6 weeks in the period October-December 2004, an
      investigator recorded how many patients took the stairs and how many took the
      elevator on the first floor of a hospital close to a diabetes outpatient clinic.
      A baseline measurement was done over a period of 2 weeks and 4 weeks were used
      for evaluating the effect of 2 different interventions, each lasting 2 weeks.
      During the first intervention, a sign was hung up near the elevator, which read:
      'Exercise is healthy, take the stairs'. During the second intervention the sign
      read: 'Use of this elevator is exclusively for personnel and persons with
      restricted mobility'. Staff members and disabled patients were excluded from the
      study. RESULTS: A total of 2674 movements were counted. Use of the stairs
      increased statistically significantly during both interventions: from 54.6% to
      63.4% during the first intervention and to 70.4% during the second intervention.
      CONCLUSION: Signs in a diabetes outpatient clinic that either encouraged the use
      of the stairs or discouraged the use of the elevator increased the patients' use
      of the stairs.

PMID- 16402519
TI  - [The treatment of oesophageal atresia in The Netherlands].
AB  - The first description of oesophageal atresia dates back to 1670. Oesophageal
      atresia used to be regarded as a lethal disease, but since the successes of Leven
      and Ladd in 1939 and Haight in 1941 surgical correction is possible. The Dutch
      history ofoesophageal atresia begins in 1946. After the successes in America
      became known, several Dutch surgeons started to treat patients with oesophageal
      atresia, notably J.ten Kate, L.D.Eerland, M. Schoorl and P.J.Kooreman. In those
      days, paediatric surgery did not yet exist as a separate specialty. Today,
      paediatric surgery is concentrated in 6 paediatric surgical centres in the
      Netherlands. Thanks to the pioneers mentioned and the concentration of knowledge
      and expertise in the centres, the mortality ofoesophageal atresia patients in the
      Netherlands has decreased to approximately 9%, despite the fact that currently
      the gestational age and birth weight of patients is lower and the number of
      patients with comorbidity is higher.

PMID- 16402520
TI  - [Enigmas surrounding an obstetric forceps belonging to Albertus Titsingh (1714
      1790)].
AB  - In the collections of the Society of the Dutch Journal of Medicine there is a
      small box containing a small obstetric forceps modelled on that of the British
      physician Smellie and some documents with information about its origin. The
      instrument belonged to the Amsterdam surgeon-obstetrician Albertus Titsingh and
      is claimed in the documentation to have been used during the birth of the later
      King William I (1772-1843) in 1772. However, historical research indicates that
      this is very unlikely: it is an established fact that the birth of William I was
      rapid and successful, while Albertus Titsingh was an authoritative obstetrician
      in an 'obstetric climate' of biding one's time and taking no action until the
      natural powers have failed.

PMID- 16402521
TI  - [The discovery of the tubercle bacillus by Robert Koch: a milestone for 123
      years].
AB  - The discovery of the tubercle bacillus and its causal relationship to
      tuberculosis by the general practitioner Robert Koch (1843-1910) in 1882 was
      truly a revolutionary discovery by a pioneer. This discovery was very well
      documented, making use of optical equipment that had just appeared on the market,
      and was accomplished in his own home without outside support. In spite of the
      publication of the discovery in a German medical periodical with only local
      circulation, the entire scientific world quickly became aware of this fundamental
      discovery. Koch was relieved from his position as a provincial general
      practitioner and given a position in a scientific institute in Berlin where he
      later occupied a central position. Also because of his work on anthrax and
      cholera, he can be considered a founder of medical bacteriology and was justly
      awarded the Nobel Prize for Medicine in 1905. A shadow was thrown over all this
      by his misunderstanding about tuberculin, which he erroneously considered to be a
      potential medicine against tuberculosis.

PMID- 16402522
TI  - [The eyes of Johann Sebastian Bach].
AB  - Limited vision seems to have been Johann Sebastian Bach's (1685-1750) only
      physical problem. Myopia seems the most likely cause and he probably developed
      cataracts later in life. In addition to the cataracts, his worsening vision may
      have been due in part to some other eye problem. In 1750 Bach's vision became so
      poor that he had his eyes operated on by the travelling English eye surgeon John
      Taylor. Most likely the first operation was Taylor's standard couching procedure.
      About one week after the first operation, Bach was operated on again because of
      the reappearance of the cataract. Many painful and/or vision-reducing
      complications could have been induced by these intraocular operations: uveitis or
      endophthalmitis, secondary glaucoma, haemorrhage, retinal detachment, and even
      sympathetic ophthalmia. After the second operation Bach was blind. He died less
      than four months later.

PMID- 16402523
TI  - [Surgeons among the pirates in the 17th century].
AB  - The memoirs of ship's surgeons that sailed with the Caribbean buccaneers and
      pirates of the 17th century are an important source of information on how they
      lived and worked. The surgeons enjoyed a full-fledged position among the
      egalitarian buccaneers. Known buccaneer surgeons whose memoirs have been
      preserved were apparently not entirely qualified according to the traditional
      guild system. Besides the usual work of ship's surgeons in general, the buccaneer
      surgeons had to be able to cope with the specific demands of the tropical
      climate. Botanical knowledge obtained from the Indian tribes played an important
      role in surviving the jungles of Central America. In addition, they were required
      to assist with duels, which played an important role among pirates and buccaneers
      in the settling of conflicts aboard ship, this in contrast to the situation on
      merchant and navy ships.

PMID- 16402524
TI  - ['Gold standard', not 'golden standard'].
AB  - In medical literature, both 'gold standard' and 'golden standard' are employed to
      describe a reference test used for comparison with a novel method. The term 'gold
      standard' in its current sense in medical research was coined by Rudd in 1979, in
      reference to the monetary gold standard. In the same way that the monetary gold
      standard allowed for the comparison of different currencies, the medical gold
      standard allowed for the comparison of different diagnostic tests. Whereas the
      gold standard was never regarded as infallible, the incorrect term 'golden
      standard' implies a level of perfection that is unattainable in medical science.
      Consequently, the correct term should be 'gold standard'.

PMID- 16402525
TI  - [Image of the month: a development and symptomatic tubular pregnancy].

PMID- 16402526
TI  - [Intrapulmonary lung sequestration: a case report].
AB  - Through the presentation of a classical case of intrapulmonary pulmonary
      sequestration, the nosology of congenital lung malformations is reviewed. The
      histology, imaging, and surgical treatment of this congenital anomaly are briefly
      discussed.

PMID- 16402527
TI  - [Well differentiated neuroendocrine carcinoma of the stomach: a case report].
AB  - Gastric well differentiated endocrine carcinomas were previously believed to be
      rare lesions, representing less than 1% of gastric neoplasms. These tumours are
      often associated with chronic atrophic gastritis, rarely with Zolling-Ellison
      syndrome. Some sporadic lesions are rarely reported. The prognosis is relatively
      good, but sporadic forms are more aggressive. We report a case of gastric
      endocrine carcinoma developed by a 52 year-old man classified as sporadic form
      after many investigations. Through this observation and after a review of
      literature, the clinicopathologic features of these tumours, their histogenesis
      and clinical behaviour are reviewed and discussed.

PMID- 16402528
TI  - [Perforation of the nasal septum in cocaine abusers].
AB  - Cocaine has been used for centuries for its stimulating and euphoric effects, but
      it also possesses vasoconstrictive and thrombotic properties. The cocaine-induced
      lesions depend mainly on the method of administration. In the present case, in
      which cocaine was nasally inhaled, the perforation of the cartilaginous nasal
      septum propably result from a combination of factors, including the topical
      effects and the complications linked to the use of the drug. This clinical
      observation corresponds to a high level of the progressive nasal pathology
      associated with cocaine abuse.

PMID- 16402529
TI  - [The impact of mental disorders on daily functioning in the Belgian community.
      Results of the study "European Study on Epidemiology of Mental Disorders"
      (ESemeD)].
AB  - AIMS: This study reports the impact of mental disorders on daily functioning in
      the Belgian population. MATERIAL AND METHOD: A representative sample of 2419 non
      institutionalised Belgian adults (18+) was interviewed between 2001 and 2002
      using the Composite International Diagnostic Interview of the World Mental Health
      Surveys of the World Health Organisation (WMH-CIDI). Common mental disorders
      (mood, anxiety, and alcohol disorders--according to DSM-IV) and functional
      disabilities (according to the World Health Organization Disablement Assessment
      Scale--WHO-DAS-2) were assessed. RESULTS: Mood and anxiety disorders were
      associated with substantial levels of disability: social, emotional and physical
      domains were affected. Mood disorders were found to exert the largest impact in
      different domains of daily functioning, although the social life was most
      affected. Anxiety disorders were, on the contrary, more associated with emotional
      and physical discomfort. Persons with a alcohol disorder reported a substantially
      low impact on their daily functioning. CONCLUSIONS: Mental disorders affect
      several domains of daily functioning, with considerable limitations in personal
      and social life, but also with dramatic cutbacks in work productivity.

PMID- 16402530
TI  - [Retrospective study of childhood lymphomas. Report of 27 children treated at a
      single institution].
AB  - Childhood lymphomas represent a heterogeneous group of disorders that are quite
      different from adult lymphomas. Over the past three decades, empirical
      chemotherapeutic management has transformed survival figures, and more recently
      greater understanding of the biology is offering hope for improved management of
      resistant disease. We present here the experience of a single institution in the
      management of 27 childhood lymphomas; epidemiological and clinical
      characteristics are described as well as survival rates. The median follow up of
      the patients is 4 years 7 months. The five-year overall survival for the entire
      group is more than 95 %; the 5-year disease free survival is 91,6 % for Hodgkin's
      lymphomas, 92,8% for non Hodgkin's lymphomas and 100% for Burkitt diseases. Two
      relapses have occurred and all of them appeared within the 18 months of the
      diagnosis. No toxic death has been reported.

PMID- 16402531
TI  - [Stop smoking help: a need].
AB  - Today the smoker carries a risk of mortality 70% higher compared to the
      nonsmoker. In Belgium active smoking is indisputably the most important cause of
      avoidable death. In 2004 it appears that 27% of the belgian population was
      smoking. This review describes the comorbidity associated with active tobacco
      consumption and defines the concepts of dependence and smoking cessation. It also
      identifies the three factors which determine the success of smoking cessation,
      i.e. the degree of nicotinic dependence, the presence of anxio-depressive
      disorders and the importance of the motivation to the stop.

PMID- 16402532
TI  - [Alveolar echinococcosis].
AB  - Alveolar echinococcosis is a serious parasitic disease, leading to large hepatic
      lesions. It must be distinguished from cystic echinococcosis, or hydatic cyst,
      caused by Echinococcus granulosus. Early diagnosis may allow surgical removal of
      the lesions by segmental hepatectomy, the only curative treatment. Parasitostatic
      medical treatment with albendazole may promote stabilization of the disease.
      Until recently, Belgium was considered a country at very low risk for alveolar
      echinococcosis, as no human case was reported, despite up to 51% of fox infection
      in southern Belgium autopsy series. Recently four patients presented with
      alveolar echinococcosis at the University Hospital Center of Liege, leading to
      the fear of a possible alveolar echinococcosis endemy in southern Belgium. Two of
      these patients underwent curative hepatectomy, but the other two had already
      pulmonary metastases at diagnosis and received palliative albendazole therapy.
      This article presents these cases, and reviews the clinical features of this
      parasitic disease.

PMID- 16402533
TI  - [The cost of complicated acute urinary retention: a patient chart analysis in
      Belgium].
AB  - OBJECTIVES: Acute Urinary Retention (AUR) is a troublesome event in patients with
      benign prostate hyperplasia and often results in adenectomy, associated with
      increased morbidity and mortality. The objective of this study is to document the
      current medical practice and resource utilization in AUR, with Belgium as a case
      setting. METHODS: In this study, a retrospective patient chart review, the 6
      month medical resource use of 63 patients hospitalised in 5 different centres
      with a first episode of AUR and failing a first attempt to remove the catheter
      (defined as complicated AUR) was recorded and costs were calculated from the
      public health care payer's perspective. Only direct medical costs (2002 values)
      were taken into account. RESULTS: The 6 month cost of complicated AUR was Euro
      6,766 (St. Err: Euro 491), whereas the cost of hospitalisation for the acute
      event was Euro 4,722 (St. Err: Euro 526). The cost of a transurethral resection
      of the prostate (TURP) performed during the index hospitalisation is much higher
      than the cost of a TURP performed during a subsequent--scheduled--hospitalisation
      (Euro 6,101 vs. Euro 4,237). CONCLUSIONS: The cost of complicated AUR is quite
      important. Preventing AUR or improving the medical management of AUR may reduce
      the number of adenectomies that have to be performed, and thus, may reduce
      mortality, morbidity and health care costs.

PMID- 16402534
TI  - [Vulvovaginal candidiasis: prevalence of different Candida species in the Liege
      region].
AB  - We calculated the prevalences of different yeast species isolated from more than
      20,000 vulvovaginal specimens carried out at the CHR hospital in Liege. To assess
      the value of the observed relative frequencies, the culture results of 149
      samples were confronted with those of a real-time PCR technique of fungal
      identification. With a prevalence close to 90%, Candida albicans remains the
      largely dominant species. In contrast with other teams, we observed no increase
      of the prevalences of Candida non-albicans species.

PMID- 16402535
TI  - [Cutaneous adverse effects of lithium].
AB  - Oral administration of lithium is used as treatment in psychiatry. The drug
      frequently induces cutaneous side effects corresponding to acneiform or maculo
      papular eruptions, psoriasis and folliculitis. Men are more frequently affected
      than women. These manifestations are characterized by the accumulation of
      neutrophils in the skin. Alopecia and classical drug reactions are also possible.
      Topical applications of lithium used to treat some dermatoses do not induce
      similar side effects, probably because dosages are much lower.

PMID- 16402536
TI  - [Chronic anemia in inflammatory bowel diseases: review].
AB  - Chronic anemia has been considered as an overlooked complication of inflammatory
      bowel disease (IBD). However it deserves full attention since even mild to
      moderate anemia has significant impact on quality of life. During the past decade
      relevant progress has been made in the understanding and treatment of this
      pathology. In our review, we focus on frequency, mechanisms, diagnosis and
      treatment of anemia in IBD.

PMID- 16402537
TI  - [The calcipotriol-betamethasone dipropionate association].
AB  - The topical treatment of psoriasis benefits from the alternate use of
      dermocorticosteroids and vitamin D3 analogues. A new galenic formulation allows
      to combine them in a single application. Dovobet (LEO Pharma) ointment is the
      association of calcipotriol 50 microg/g with betamethasone dipoprionate 0.5 mg/g.
      This formulation boosts the therapeutic activity of calcipotriol. It also
      decreases the irritative inflammatory reaction due to calcipotriol without
      increasing the atrophogenic risk of the dermocorticoid.

PMID- 16402538
TI  - [Proactive study: secondary cardiovascular prevention with pioglitazione in type
      2 diabetic patients].
AB  - PROactive is a prospective, randomised controlled trial in 5238 patients with
      type 2 diabetes who had evidence of macrovascular disease. Patients were assigned
      to oral pioglitazone titrated from 15 mg to 45 mg or matching placebo, to be
      taken in addition to their glucose-lowering drugs and other medications. After a
      mean follow up of 34.5 months, pioglitazone reduced the composite of all-cause
      mortality, non-fatal myocardial infarction, and stroke (intention to treat
      analysis: hazard ratio = 0.84; 95% CI: 0.72-0.98; p = 0.027). Various favourable
      metabolic effects could contribute to this cardiovascular protection, i.e. an
      absolute 0.5 % reduction in HbA1c, a 9% increase in HDL cholesterol, a 13%
      decline of triglycerides, and a 3 mm Hg reduction in systolic blood pressure in
      the pioglitazone group compared to placebo. The requirement of insulin was
      reduced by almost 50% in the pioglitazone group as compared to the placebo group.
      The incidence of cases of oedema and congestive heart failure was higher in the
      pioglitazone group. In conclusion, in patients with type 2 diabetes who are at
      high cardiovascular risk, pioglitazone improves cardiovascular outcome, and
      reduces the need to add insulin to glucose-lowering regimens compared to placebo.

PMID- 16402539
TI  - Bioactive saponins from Astragalus suberi L. growing in Yemen.
AB  - From the aerial parts of Astragalus suberi L., Fabaceae, seven saponins were
      isolated. Based on spectral data (IR, 1H and 13C NMR and HR-FABMS), the
      structures were established as 3-O-(beta-D-glucopyranosyl)-soyasapogenol B (1); 3
      O-(beta-D-glucuronopyranosyl)-soyasapogenol B (2); 3-O-[beta-D-galactopyranosyl
      (1-->2)-beta-D-glucopyranosyl]-soyasapogenol B (3); 3-O-[alpha-L-rhamnopyranosyl
      (1-->2)-beta-D-galactopyranosyl (1-->2)-beta-D-glucopyranosyl]-soyasapogenol B
      (4); 3-O-[beta-L-rhamnopyranosyl (1-->2)-beta-D-galactopyranosyl (1-->2)-beta-D
      glucopyranosyl]-11-hydroxy-soyasapogenol B (5); 3-O-[alpha-L-rhamnopyranosyl (1-
      >2)-beta-D-galactopyranosyl (1-->2)-beta-D-glucuronopyranosyl]-soyasapogenol B
      (6) and 3-O-[alpha-L-rhamnopyranosyl (1-->2)-beta-D-galactopyranosyl (1-->2)-beta
      D-glucuronopyranosyl]-complogenin (7). The isolated saponins exhibited
      antibacterial activities against Gram-positive and Gram-negative bacteria with
      minimum inhibitory concentration values >100 microg/ml, antifungal activity
      against all the strains tested with minimum fungicidal concentration values
      between 25 and 50 microg/ml and inhibited the growth of Hep-2 (human carcinoma of
      larynx), with IC50 values between 50 microg/ml (compounds 5-7) and 100 microg/ml
      (compounds 1-4), and Hela (human carcinoma of cervix) cell lines in culture with
      different IC50 values [74 (compound 7), 98 (compound 5) and 180 microg/ml
      (compounds 1-4 and 6)].

PMID- 16402540
TI  - Essential oil composition and antimicrobial activity of Diplotaenia damavandica.
AB  - Antimicrobial activity of the essential oils obtained from leaves, root and the
      seeds of Diplotaenia damavandica Mozaffarian, Hedge & Lamond, an endemic plant to
      Iran, was determined against 10 microorganisms using the disk susceptibility test
      as well as measuring minimum inhibitory concentrations. The results showed that
      all three oils had antibacterial activity against Bacillus subtilis,
      Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli. The
      essential oil from the leaves had the highest antimicrobial activity against all
      test microorganisms including the fungal strains. The essential oils compositions
      were analyzed and determined by GC and GC-MS. The oils analyses resulted in the
      identification of 16, 17 and 20 compounds representing 94.2%, 96.4% and 95.1% of
      the total oils, respectively. The main components of the leaf essential oils were
      (Z)-beta-ocimene (21.6%), alpha-phellandrene (21.3%) and terpinolene (20%). Dill
      apiol (30.1%) and gamma-terpinene (16.2%) were the main components of the root
      and seed essential oils, respectively.

PMID- 16402541
TI  - Antiradical and anti-H2O2 properties of polyphenolic compounds from an aqueous
      peppermint extract.
AB  - Polyphenolic compounds such as eriocitrin, luteolin-7-O-rutinoside, diosmin,
      hesperidin, narirutin, isorhoifolin, rosmarinic and caffeic acids were identified
      in an aqueous extract (Ex) obtained from peppermint leaves (Menthae x piperitae
      folium). The content of polyphenols in Ex was as follows: eriocitrin 38%,
      luteolin-7-O-rutinoside 3.5%, hesperidin 2.9%, diosmin 0.8%, isorhoifolin 0.6%,
      narirutin 0.3%, rosmarinic acid 3.7% and caffeic acid 0.05%. The strongest
      antiradical activity (determined as DPPH* scavenging features) was observed for
      luteolin-7-O-rutinoside, eriocitrin and rosmarinic acid. Caffeic acid and
      hesperidin revealed a lower antiradical activity while isorhoifolin, narirutin
      and diosmin showed the lowest activity. The strongest anti-H2O2 activity was
      observed for eriocitrin, a little lower for rosmarinic acid. The rate of hydrogen
      peroxide scavenging activity displayed by luteolin-7-O-rutinoside and caffeic
      acid was lower than that of rosmarinic acids. Hesperidin appeared to be a very
      weak scavenger of hydrogen peroxide. Almost no anti-H2O2 activity was
      demonstrated for diosmin, narirutin and isorhoifolin. Among examined flavonoids,
      the strongest antiradical and anti-H2O2 activity was shown for compounds with two
      hydroxy groups bound to the Bring in ortho position in relation to each other.
      Replacement of one hydroxy group in the Bring with a methoxy group or removing
      one hydroxy group leads to decrease of antiradical and anti-H2O2 activity of
      flavonoids. Our results suggest that eriocitrin is a powerful peppermint
      antioxidant and a free radical scavenger.

PMID- 16402542
TI  - Antioxidative and antiradical properties of plant phenolics.
AB  - The plant phenolic compounds such as flavonoids, tannins and phenolic acids
      appeared to be strong antiradical and antioxidant compounds. The number of
      hydroxy groups and the presence of a 2,3-double bond and orthodiphenolic
      structure enhance antiradical and antioxidative activity of flavonoids. The
      glycosylation, blocking the 3-OH group in C-ring, lack of a hydroxy group or the
      presence of only a methoxy group in B-ring have a decreasing effect on
      antiradical or antioxidative activity of these compounds. Tannins show strong
      antioxidative properties. Some tannins in red wine or gallate esters were proved
      to have antioxidative effect in vivo. The number of hydroxy groups connected with
      the aromatic ring, in ortho or para position relative to each other, enhance
      antioxidative and antiradical activity of phenolic acids. The substitution of a
      methoxy group in ortho position to the OH in monophenols seems to favour the
      antioxidative activity of the former.

PMID- 16402543
TI  - Isolation and evaluation of tannin-degrading fungal strains from the Mexican
      desert.
AB  - Eleven fungal strains (4 Penicillium commune, 2 Aspergillus niger, 2 Aspergillus
      rugulosa, Aspergillus terricola, Aspergillus ornatus and Aspergillus fumigatus)
      were isolated, characterized morphologically and by their capacity to degrade
      tannins. Aspergillus niger Aa-20 was used as control strain. Several
      concentrations of hydrolysable tannin (tannic acid) were used as sole carbon
      source. All strains were able to degrade hydrolysable tannins. Aspergillus niger
      GH1 and PSH showed the highest tannin-degrading capacity (67 and 70%,
      respectively). Also, the fungal capacity to degrade condensed tannin (catechin)
      was tested. Aspergillus niger PSH and Penicillium commune EH2 degraded 79.33% and
      76.35% of catechin. The results demonstrated the capacity of fungi to use
      hydrolysable and condensed tannins as carbon source.

PMID- 16402544
TI  - Redox properties of novel antioxidant 5,8-Dihydroxycoumarin: implications for its
      prooxidant cytotoxicity.
AB  - The aim of this work was to characterize the redox properties of the new
      antioxidant 5,8-dihydroxycoumarin (5,8-DHC), isolated from sweet grass
      (Hierochloe odorata L.), and to determine its impact on its cytotoxic action.
      Reversible electrochemical oxidation of 5,8-DHC at pH 7.0 was characterized by
      the midpoint potential (E(p/2)) of 0.23 V vs. the normal hydrogen electrode. 5,8
      DHC was slowly autoxidized at pH 7.0, and it was active as a substrate for
      peroxidase (POD, EC 1.11.1.7) and tyrosinase (TYR, EC 1.14.18.1). Oxidation of
      5,8-DHC by POD/H202 yielded the product(s) which reacted with reduced glutathione
      and supported the oxidation of NADPH by ferredoxin:NADP+ reductase (FNR, EC
      1.18.1.2) and NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase, EC 1.6.99.2).
      The concentration of 5,8-DHC for 50% survival of bovine leukemia virus
      transformed lamb kidney fibroblasts (line FLK) during a 24-h incubation was (60
      +/- 5.5) microM. Cytotoxicity of 5,8-DHC was decreased by desferrioxamine,
      catalase, the antioxidant N,N'-diphenyl-p-phenylene diamine, and potentiated by
      1,3-bis-(2-chloroethyl)-1-nitrosourea and dicumarol, an inhibitor of NQO1. This
      shows that 5,8-DHC possesses the oxidative stress-type cytotoxicity, evidently
      due to the action of quinodal oxidation product(s). The protective effect of
      isoniazide, an inhibitor of cytochrome P-450 2E1, points to hydroxylation of 5,8
      DHC as additional toxification route, whereas the potentiating effect of 3,5
      dinitrocatechol, an inhibitor of catechol-o-methyltransferase (COMT, EC 2.1.1.6),
      points to the o-methylation of hydroxylation products as the detoxification
      route.

PMID- 16402545
TI  - Antifeedant/insecticidal terpenes from asteraceae and labiatae species native to
      Argentinean semi-arid lands.
AB  - To validate the potential as added-value resources of Asteraceae and Labiatae
      species of Argentinean semi-arid lands, we have selected 13 of their major
      terpenoids belonging to several chemical classes and tested their insect
      antifeedant and toxic activity on the herbivorous insects Spodoptera littoralis
      and Leptinotarsa decemlineata. The antifeedant effects of the test compounds were
      structure- and species-dependent. The most active antifeedant to L. decemlineata
      was the eudesmane sesquiterpene gamma-costic acid (13), followed by the labdane
      diterpene 2alpha,3alpha-dihydroxycativic acid (8), the clerodane diterpenes 6
      acetylteucjaponin B (5), bacchotricuneatin A (1), bartemidiolide (7), butanolide
      (4), and the sesquiterpenes ilicic acid (11) and tessaric acid (10) (eudesmane
      and eremophilane type, respectively). S. littoralis was only affected by the
      clerodanes and showed the strongest response to salviarin (3) and 5, followed by
      hawtriwaic acid (6) and 12-epi-bacchotricuneatin A (2). Orally injected S.
      littoralis larvae were negatively affected by 5. Most of the diterpenes had
      selective cytotoxic effects to insect-derived Sf9 cells with the clerodane 1
      being the most active, followed by the eudesmane costic acid (12), the only
      cytotoxic sesquiterpene. None of these compounds was cytotoxic to mammalian CHO
      cells.

PMID- 16402546
TI  - Phytotoxic components produced by pathogenic Fusarium against morning glory.
AB  - A pathogenic isolate of Fusarium, F. oxysporum f. sp. batatas O-17 (PF), causes
      wilt disease in leaf etiolation in sweet potato (Ipomoea batatas) and morning
      glory (Ipomoea tricolor). Extracts from PF cultures were screened for phytotoxic
      components using a growth inhibition assay with morning glory seedlings. The
      extracts were fractionated using differential solvent extraction and two active
      compounds, ergosterol and fusalanipyrone, were isolated from the less-polar
      fraction. Growth inhibition of morning glory seedlings showed a sigmoidal dose
      response relationship, with fusalanipyrone exhibiting a two order of magnitude
      higher EC50 value than ergosterol (18 nM and 1.6 microM, respectively). Both
      compounds showed lower growth inhibition activity towards lettuce seedlings
      (Lactuca sativa). This study provides information on the phytotoxic components of
      PF and discusses the mechanism behind PFf-induced phytotoxicity.

PMID- 16402547
TI  - Genista tinctoria hairy root cultures for selective production of
      isoliquiritigenin.
AB  - Hairy root cultures were established after inoculation of Genista tinctoria in
      vitro shoots with Agrobacterium rhizogenes, strain ATCC 15834. In transformed
      roots of G. tinctoria grown in Schenk-Hildebrandt medium without growth
      regulators the biosynthesis of isoflavones, derivatives of genistein and
      daidzein, and flavones, derivatives of luteolin and apigenin, characteristic for
      the intact plant, was completely inhibited. The only compound synthesized in G.
      tinctoria hairy roots was isoliquiritigenin (2.3 g/100 g DW), a daidzein
      precursor absent in the intact plant. This compound was stored entirely within
      cells and it was not until abscisic acid was added (37.8 microM supplement on day
      42) that approx. 80% of it was released into the experimental medium. The paper
      discusses the effect of abscisic acid on the growth of G. tinctoria hairy root
      cultures, the biosynthesis of isoliquiritigenin and the way it is stored. A
      prototype basket-bubble bioreactor was designed and built to upgrade the scale of
      the G. tinctoria hairy root cultures. With immobilized roots and a new aeration
      system, large amounts of biomass were obtained (FWmax 914.5 g l(-1)) which
      produced high contents of isoliquiritigenin (2.9 g/100 g DW). The abscisic acid
      induced release of the metabolite from the tissue into the growth medium greatly
      facilitated subsequent extraction and purification of isoliquiritigenin.

PMID- 16402548
TI  - The effect of electric field on callus induction with rape hypocotyls.
AB  - The influence of electric field treatment on dedifferentiation and calli
      formation on rape hypocotyls was investigated. Segments, 10 mm long, of the upper
      part of rape (Brassica napus L., cv. Goczanski) hypocotyls were stimulated by
      different combinations of voltage/time (1.5 V/120 h, 3 V/3 h, 10 V/15 min and 30
      V/30 s) under in vitro conditions. With all electric field treatments, segments
      oriented with their apical part towards the cathode produced more calli as
      compared to control (non-treated with electric field). Under opposite orientation
      slight inhibition of callus growth was observed. As the strongest effect on
      callus growth was observed after treatment with 30 V/30 s, this electric field
      treatment was selected for following analyses: the incorporation of [14C]-2,4-D
      (2,4-dichlorophenoxyacetic acid) and [14C]-BAP (benzylaminopurine) from the
      culture medium, changes in ACC (1-aminocyclopropane-1-carboxylic acid) level and
      the redox activity in apical and bottom parts of hypocotyls during 18 d of
      culture. In contrast to changes in fresh weight, electric field treatment (30
      V/30 s) stimulated a higher accumulation of 2,4-D and BAP in basal parts of
      hypocotyls than in apical ones. Moreover, orienting the apical part towards the
      cathode resulted in lower uptake of hormones as compared with the opposite
      orientation. The ACC concentration increased, especially in the basal parts of
      hypocotyls, independently on electric field application. However, the highest
      level was observed after electric field treatment with orientation of the apical
      part towards the anode. The distribution of oxidative substances (measured as the
      amount of ferric ions) between the apical and bottom part of hypocotyls was not
      changed when the apical parts were oriented towards the cathode. Under these
      conditions a decrease in apical and an increase in basal parts was observed
      during culture. Opposite orientation influenced the redistribution of oxidative
      substances from the first day of electric field treatment. Based on these results
      we suggest that electric field action can be connected with its influence on
      specific concentration of oxidative substances and hormone distribution in cells.

PMID- 16402549
TI  - Metabolism of 4-n-nonylphenol by non-modified and CYP1A1- and CYP1A2-transgenic
      cell cultures of tobacco.
AB  - The metabolism of 14C-4-n-nonylphenol (l4C-4-n-NP), as a model for the
      xenoestrogen nonylphenol, was investigated in three types of tobacco cell
      suspension cultures: one genetically non-modified culture (NT) and two cultures
      constitutively expressing human cytochrome P450 CYP1A1 or CYP1A2. With 1 mg l(-1)
      of 14C-4-n-NP and 24 h of incubation, the xenobiotic was transformed almost
      completely to glycosides. After glycosidic cleavage, 14C-4-n-NP and several
      primary metabolites of 4C-4-n-NP were liberated. Portions of the primary
      metabolites were 29.3% (NT culture), 34.3% (CYP1A1 culture), and 50.7% of applied
      14C (CYP1A2 culture). Thus, the endogenous capacity of the tobacco cells to form
      primary metabolites of 4-n-NP was noticeably higher than that of CYP1A1 or
      CYP1A2. The results however clearly suggest that 4-n-NP is - even though a poor -
      substrate of CYP1A1 and CYP1A2. In order to examine metabolic profiles of 4-n-NP
      in the NT, CYP1A1 and CYP1A2 cultures, the suspensions were exposed to 10 mg 1(
      1) of 14C-4-n-NP using a two-liquid-phase system with carrier n-hexadecane and
      192 h of incubation. Results obtained resembled those of the low concentration
      study. The oxidative metabolic profiles determined after hydrolytic cleavage
      using GC-EIMS were similar in the NT, CYP1A1 and CYP1A2 cultures. Main
      metabolites were side-chain mono-hydroxylated derivatives of 4-n-NP with 6'-, 7'-
      and 8'-OH-4-n-NP as prominent metabolites. In addition, olefinic side-chain
      hydroxy, ring methoxylated, keto and ring hydroxylated derivatives were observed.
      The lack of differences in metabolic profiles among the CYP1A1, CYP1A2 and NT
      cultures was referred to the low enzymatic activity of CYP1A1 and CYP1A2 as
      compared to the higher endogenous oxidative capacity of tobacco, as well as to
      similar metabolic profiles of 4-n-NP produced by CYP1A1 and CYP1A2 and tobacco
      itself.

PMID- 16402550
TI  - New host plants of Erwinia amylovora in Bulgaria.
AB  - Nine strains of Erwinia amylovora were isolated from new host plants in Bulgaria-
      chokeberry and strawberry. The strains were characterized morphologically and
      biochemically using the API 20E and BIOLOG system. It was established that they
      showed three different API 20E metabolic profiles, not found by previous studies
      of E. amylovora. All strains were identified as E. amylovora due to their
      metabolic fingerprint patterns obtained by the BIOLOG system. The identification
      was confirmed by PCR amplification of a specific region of plasmid pEA29 and
      genome ams-region. This study is the first characterization and identification of
      E. amylovora strains isolated from chokeberry and strawberry by the API 20E and
      BIOLOG system and by polymerase chain reaction.

PMID- 16402551
TI  - Oligogalacturonate hydrolase from carrot roots.
AB  - The presence of multiple forms of enzyme with terminal action pattern on pectate
      was evaluated in the protein mixture obtained from carrot roots. The form with pH
      optimum 3.8 clearly preferred substrates with a lower degree of polymerization
      (oligogalacturonates). Its molecular mass, isoelectric point, glycosylation as
      well as cleavage of pectate from nonreducing end corresponded to an
      exopolygalacturonase [EC 3.2.2.67]. The affinity of this enzyme to the substrates
      increased with the increasing degree of polymerization, and the difference was
      observed only in the maximal ratio of catalysis of oligomeric and polymeric
      substrates. Sterical hindrance for substrates with more than six D
      galactopyranuronic acid units is supposed and an oligogalacturonate hydrolase
      rather than exopolygalacturonase is considered.

PMID- 16402552
TI  - Film formation and structural characterization of silk of the hornet Vespa
      simillima xanthoptera Cameron.
AB  - We extracted silk produced by the larva of the hornet Vespa simillima xanthoptera
      Cameron from its nest. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) analysis of the extracted hornet silk showed four major components
      with molecular weights between 35 and 60 kDa. The main amino acid components of
      the hornet silk protein were Ala (33.5%), Ser (16.9%), Asp (8.5%) and Glu (8.1%).
      The hornet silk could be dissolved in hexafluoroisopropyl alcohol (HFIP) at 25
      degrees C without incurring molecular degradation. A transparent film of hornet
      silk was obtained readily by the formation of a cast upon drying of the hornet
      silk in the HFIP solution. Residual HFIP solvent was removed from the film by
      extraction with pure water. Solid-state 13C NMR and FT-IR measurements revealed
      that the secondary structures of hornet silk proteins in the native state
      consisted of coexisting alpha-helix and beta-sheet conformations. The beta-sheet
      to alpha-helix ratio, which was changed by processing, was mainly responsible for
      the silk's thermostability.

PMID- 16402553
TI  - Age related differences in lipophilic compounds found in femoral gland secretions
      of male spiny-footed lizards, Acanthodactylus erythrurus.
AB  - Although chemoreception plays an important role in social organization of many
      lizards, only a few studies have examined the chemicals found in secretions used
      for intraspecific communication. We report the composition of the secretion of
      the femoral glands of males of the spiny-footed lizard (Acanthodactylus
      erythrurus). On the basis of mass spectra, obtained by GC/MS, we identified 45
      lipophilic compounds, including several alcohols ranging from 10 to 29 carbon
      atoms (mainly hexacosanol and tetracosanol), steroids (mainly cholesterol and
      dehydrocholesterol), n-C9 to n-C20 carboxylic acids, esters of carboxylic acids,
      and minor components such as lactones, ketones, squalene and a-tocopherol. Some
      of these compounds are reported for the first time in lizards. Adult and subadult
      males differed in the composition of secretions, with C9 to C15 carboxylic acids
      being more abundant in younger than in older lizards, whereas C16 to C20
      carboxylic acids were more abundant in older lizards. Also, older lizards had
      significant lower proportions of cholesterol and campesterol but higher
      proportions of dehydrocholesterol.

PMID- 16402554
TI  - Stimulation of TNF-alpha release by fungal cell wall polysaccharides.
AB  - Carboxymethylated derivatives were prepared from the (1-->3)-beta-D-glucan
      isolated from the cell wall of baker's yeast Saccharomyces cerevisiae and from
      the chitin-glucan complex of the mycelium of the industrial filamentous fungus
      Aspergillus niger. The polysaccharides were applied to peritoneal mouse
      macrophages and after a 2-h incubation the release of TNF-alpha by the stimulated
      macrophages was measured using an enzyme-linked immunosorbent assay. As the third
      polysaccharide stimulant, a water-soluble derivative of chitin was assayed and
      the observed cytokine release was compared with the control experiment. In three
      concentrations of the polysaccharides applied, carboxymethyl glucan revealed a
      dramatic increase in the TNF-alpha release, while addition of carboxymethyl
      chitin-glucan resulted only in a moderate enhancement, and carboxymethyl chitin
      was inactive. The results indicate that fungal polysaccharides, especially (1-
      >3)-beta-D-glucan, are potent macrophage stimulators and activators of TNF-alpha
      release, which implies their potential application in antitumor therapy.

PMID- 16402555
TI  - Oligomeric structure of mammalian purine nucleoside phosphorylase in solution
      determined by analytical ultracentrifugation.
AB  - The influence of phosphate, ionic strength, temperature and enzyme concentration
      on the oligomeric structure of calf spleen purine nucleoside phosphorylase (PNP)
      in solution was studied by analytical ultracentrifugation methods. Sedimentation
      equilibrium analysis used to directly determine the enzyme molecular mass
      revealed a trimeric molecule with Mr = (90.6 +/- 2.1) kDa, regardless the
      conditions investigated: protein concentration in the range 0.02-1.0 mg/ml,
      presence of up to 100 mM phosphate and up to 200 mM NaCl, temperature in the
      range 4-25 degrees C. The sedimentation coefficient (6.04 +/- 0.02) S, together
      with the diffusion coefficient (6.15 +/- 0.11) 10(-7) cm2/s, both values obtained
      from the classic sedimentation velocity method at 1.0 mg/ml PNP concentration in
      20 mM Hepes, pH 7.0, yielded a molecular mass of (90.2 +/- 1.6) kDa as expected
      for the trimeric enzyme molecule. Moreover, as shown by active enzyme
      sedimentation, calf spleen PNP remained trimeric even at low protein
      concentrations (1 microg/ml). Hence in solution, similar like in the crystalline
      state, calf spleen PNP is a homotrimer and previous suggestions for dissociation
      of this enzyme into more active monomers, upon dilution of the enzyme or addition
      of phosphate, are incorrect.

PMID- 16402556
TI  - Alkaloids of anuran skin: antimicrobial function?
AB  - A variety of alkaloids, most of which occur or are structurally related to
      alkaloids that occur in skin glands of dendrobatid poison frogs, were assayed for
      antimicrobial activity against the Gram-positive bacterium Bacillus subtilis, the
      Gram-negative bacterium Escherichia coli and the fungus Candida albicans. Certain
      pyrrolidines, piperidines and decahydroquinolines, perhydro-histrionicotoxin, and
      a synthetic pumiliotoxin were active against B. subtilis. Only 2-n
      nonylpiperidine was active against E. coli. One pyrrolidine, two piperidines, two
      decahydroquinolines, and the synthetic pumiliotoxin were active against the
      fungus C. albicans. The results suggest that certain of the skin alkaloids of
      poison frogs, in addition to being noxious to predators, may also benefit the
      frog through protection against skin infections.

PMID- 16402557
TI  - A study on differences between radiation-induced micronuclei and apoptosis of
      lymphocytes in breast cancer patients after radiotherapy.
AB  - Cancer patients' responses to radiotherapy vary in severity. It has been
      suggested that it may be due to differences in intrinsic cellular
      radiosensitivity. Prediction of tissue reactions to radiotherapy would permit
      tailoring of dosage to each patient. Towards this goal the micronucleus and
      apoptosis tests have been proposed as methods for measurement of chromosomal
      damage in peripheral blood lymphocytes. In this study, gamma-ray sensitivity of
      cultured lymphocytes of 26 breast cancer patients with early or late reactions
      was investigated. After irradiation with 4 Gy gamma radiation in G0, the
      frequency of micronuclei for patients with early reactions was significantly
      higher (P < 0.05) than for patients with late reactions. In the contrary the
      frequency of apoptosis for patients with early reactions was significantly lower
      (P < 0.05) than in the other group. It could be suggested that such a reduced
      amount of micronuclei in the late effects group is due to the presence of some
      residual DNA damages which are not completely repaired and lesions show
      increasing severity when the patients' cells are irradiated again. These induced
      damages, probably are high enough to stimulate other endpoints like apoptosis
      instead of micronuclei.

PMID- 16402558
TI  - Two new methods monitoring kinetics of hydrolysis of acetylcholine and
      acetylthiocholine.
AB  - Hydroxylamine and HPLC methods, measuring in vitro kinetics of enzymatic
      hydrolysis of acetylcholine or acetylthiocholine by cholinesterases, are
      described. The hydroxylamine method determines the dependence of substrate
      concentration vs. time, the HPLC method is able to measure simultaneously the
      time dependences of substrate and both primary products, choline or thiocholine,
      and acetic acid. Practical determinations are shown, comparison with known (above
      all Ellman's and pH-stat) methods, advantages and disadvantages are discussed.

PMID- 16402559
TI  - Postglacial dispersal of Phlebotomus perniciosus into France.
AB  - Phlebotomus perniciosus was identified morphologically in samples from France and
      northeast Spain, and individuals were then characterized at three polymorphic
      isoenzyme loci (by isoelectrofocusing) and at the mitochondrial DNA locus (by
      comparative DNA sequence analysis of a fragment of the Cytochrome b gene). The
      four polymorphic loci gave conflicting patterns of population relationships,
      which can be explained by hypothesizing different amounts of gene introgression
      at each locus when two distinctive lineages met in southern France or northeast
      Spain after isolation in southern Italy and Spain during the Pleistocene Ice
      Ages. P. perniciosus is an important vector of leishmania infantum and so these
      population differentiation studies are relevant for predicting the emergence and
      spread of leishmaniasis in relation to environmental changes, including climate.

PMID- 16402560
TI  - [A redescription of Macrostylophora borneensis (Jordan, 1926) (Siphonaptera
      Ceratophyllidae-Ceratophyllinae), a flea of the Malaysian sub-region and
      description of an allied species].
AB  - This note redescribes M. borneensis and describes M. traubi n. sp. based on the
      known specimens from the two sampling localities (holotype from Mount Murud and
      further recorded from Mount Kinabalu by Traub). The clearly allied, but clearly
      distinct species for the two localities, were recorded.

PMID- 16402561
TI  - Influence of host sex and age on infracommunities of metazoan parasites of
      Prochilodus lineatus (Valenciennes, 1836) (Prochilodontidae) of the upper Parana
      River floodplain, Brazil.
AB  - 149 specimens of Prochilodus lineatus were collected on the upper Paran6 River
      floodplain. Of these, 121 (82.1%) were parasitized. 33 species of metazoan
      parasites were recorded. Rhinonastes pseudocapsaloideum was classified as
      secondary, while all other species were classified as satellites. Ergasilus sp.
      and Tereancistrum curimba were positively associated and their abundances were
      positively correlated. Saccocoelioides magnorchis and S. nanii were positively
      associated and their abundances were positively correlated. The mean diversity in
      the infracommunities of P. lineatus was H = 0.6875 +/- 0.4398. Host standard
      length was not correlated with parasite diversity (rs = 0.1726; p = 0.0533). The
      abundances of T. curimba and Kritskyia boegeri, and S. magnorchis and S. nanii
      were significantly correlated with host length. Correlation between fish age and
      parasite prevalence was not significant. The abundances of Amplexibranchius sp.,
      K. boegeri and S. magnorchis were significantly different among host age classes.
      For Amplexibranchius sp., the three-year old age class had more parasites. For K.
      boegeri, the intermediate age classes had the most numerous parasites. Only
      Tereancistrum curimba showed significant difference in the prevalence between the
      sexes, with females being more parasitized.

PMID- 16402562
TI  - Parasites of the squirrel Sciurus spadiceus (Rodentia: Sciuridae) from Amazonian
      Brasil, with particular reference to Eimeria damnosa n. sp. (Apicompiexa:
      Eimeriidae).
AB  - A description is given of the mature oocysts and endogenous stages of Eimeria
      damnosa n. sp. from the small intestine of the red squirrel, Sciurus spadiceus,
      from the State of Acre, north Brazil. Ten of 12 animals examined were infected.
      Oocysts ovoid to ellipsoidal, occasionally cylindrical but not with parallel
      sides, 30.2 x 20.0 microm (18.0 x 15.0-40.2 x 30.0), shape-index (ratio
      length/width) 1.5 (1.3-1.8), n = 40. Oocyst wall smooth, colourless, with no
      micropyle, apparently of a single layer measuring approximately 1.0-1.5 microm
      thick. No oocyst residuum, but approximately 50 % of the oocysts with a single
      spherical, ovoid or dumbbell-shaped polar body. Sporocysts pear-shaped, 15.0 x
      8.0 microm (11.0 x 6.0-16.0 x 8.0), shape index 1.9 (1.8-2.0), n = 33. Stieda
      body, if it merits this name, appears only as a slight thickening of the
      sporocyst wall at the more pointed extremity. Endogenous stages intracytoplasmic
      in the epithelial cells of the duodenum and throughout the ileum, above the host
      cell nucleus. Sporulation frequently completed in the lumen of the intestine, but
      most oocysts mature outside the host at some time within 24 hours. Massive
      infections may result in extensive desquamation of the gut epithelium, and
      sometimes in the death of the animal. In addition to this coccidian, one squirrel
      showed abundant trophozoites of a Giardia sp., in the ileum. The liver of two
      others contained developing and mature meronts, producing large numbers of
      slender merozoites, and other cyst-like bodies containing a small number of large
      zoites (sporozoites?). No parasites were detected in the blood of any of the
      squirrels that could be associated with this unidentified protozoan. Histological
      sections of the ileum of one squirrel revealed a globidium-like parasite in the
      lamina propria: it contained a very large number of slender, curved zoites. Three
      animals were with a sheathed microfilaria in the peripheral blood and liver
      smears. Finally, a Trypanosoma cruzi-like trypanosome was isolated from the blood
      of one squirrel and a T. lewisi-like trypanosome from two others.

PMID- 16402563
TI  - Factors affecting helminths community structure of the Egyptinan lizard Chalcides
      ocellatus (Forskal, 1775).
AB  - The variation in the component community structure of intestinal helminths in the
      lizard Chalcides ocellatus (Forskal, 1775) was studied in relation to the
      seasonal variation and host weight and sex. 120 lizards were collected seasonally
      during year 2004, from Al Firdan, Ismailia governorate, Egypt. The helminths
      community consisted of six species (five nematodes and one cestode). The various
      helminths differed according to host sex. The prevalence of total helminths
      infection was 67.6 % while the prevalences of Thelandros schusteri, Pharyngodon
      mamillatus, Parapharyngodon bulbosus, Cosmocerca vrcibradici, Spauligodon petersi
      and Oochoristica maccoyi were 43.4%, 3.9 %, 13.2%, 5.3%, 6.6%, and 14.3%,
      respectively. The results showed that the season was the main factor affecting
      infracommunity species richness and parasite abundance. Moreover, there was
      interaction between season and host sex on abundance of P. bulbosus. The
      prevalence of intestinal helminths varied significantly in relation to host
      weight classes and sex in some species. Helminths abundance and intensity were
      independent from host sex. In addition, correlations were found between total
      helminths abundance and host weight. In conclusion, the helminths community of C.
      ocellatus was depauperate and the influence of the studied factors varied from
      species to another one. We cannot say if the low species richness and infection
      rates observed in the present study are typical of the host species or if they
      are due to characteristics of the study area, since no available data on parasite
      assemblages exist for other C. ocellatus populations.

PMID- 16402564
TI  - Monogeneans from Pangasiidae (Siluriformes) in Southeast Asia: IX. Two new
      species of Thaparocleidus Jain, 1952 (Ancylodiscoididae) from Pangasius
      mahakamensis.
AB  - The examination of gill parasites from P. mahakamensis Pouyaud, Gustiano &
      Teugels, 2002 (Siluriformes, Pangasiidae) in Southeast Asia revealed the presence
      of three species of Monogenea. One (Thaparocleidus caecus (Mizelle & Kritsky,
      1969)) had been previously described. The other two, belonging to Thaparocleidus
      Jain, 1952 (Monogenea, Ancylodiscoididae) as defined by Lim (1996) and Lim et al.
      (2001), are considered new species: T. pouyaudi n. sp. and T. teugelsi n. sp.

PMID- 16402565
TI  - Description of two new species of Nippostrongylinae (Nematoda, Trichostrongyuna,
      Heligmosomoidea) coparasites in Arvicanthis ansorgei (Muridae) from Cameroon.
AB  - In the small intestine of a single Arvicanthis ansorgei from Cameroon, two new
      species of Nippostrongylinae were found: Neoheligmonella zero n. sp. and
      Heligmonina comerounensis n. sp. N. zero belongs to the Neoheligmonella species
      in which the right dorsal ridge is poorly developed. Among these species, N.
      bainae (Durette-Desset, 1970), a parasite of Steatomys opinus from Burkina Fasso,
      is a closely related species. It is differentiated by the presence of vulvar
      alae, the ratio uterus length/body length and the separation of rays 2 and 3 at
      two thirds of their length. N. zero is also closely related to N. kenyae (Yeh,
      1958) a parasite of Rattus rattus kijabius from Kenya by the pattern of the
      caudal bursa and the ratio spicules length/body length. The synlophe of N. kenyae
      was not described in detail but it is differentiated from N. zero by the position
      of the excretory pore, situated just posteriorly to the nerve ring and in the
      female by the ratio ovejector length/body length which is smaller. H.
      camerounensis n. sp. is characterised by the ratio dorsal ridges/ventral ridges
      which is 4/7. It is differentiated from the species of which the synlophe has not
      been described by the pattern of the caudal bursa (type 1-4 with tendancy 1-3-1).
      It is the first report of Nippostrongylinae species in Cameroon and the first
      record of a species of the genus Heligmonina in an Arvicanthis.

PMID- 16402566
TI  - Echinococcus multlocularis infections of rural, residential and urban foxes
      (Vulpes vulpes) in the canton of Geneva, Switzerland.
AB  - We examined 267 red foxes (Vulpes vulpes) from the canton of Geneva, Switzerland,
      for intestinal infections with Echinococcus multilocularis. This region is
      situated in the core area of the endemic range of this zoonotic cestode in
      Central Europe. Several factors were taken into account and urbanisation level
      appeared to be the most explicative to describe observed differences. The
      prevalence decreased significantly from rural and residential areas (prevalence
      of 52%, CI 43-62%, and 49%, CI 38-59 %, respectively) to the urban area
      (prevalence of 31%, CI 19-42%). A few juvenile foxes harboured very high burdens
      up to more than 120,000 worms and were significantly more heavily infected than
      adults. The intensity of infection decreased from rural and residential areas to
      the city, suggesting a lower contamination of the urban environment.

PMID- 16402567
TI  - Poor efficacy of the most commonly used anthelmintics in sport horse nematodes in
      Morocco in relation to resistance.
AB  - Sport and leisure horses in Morocco are treated with several anthelmintics,
      organophosphates (dichlorvos), benzimidazoles (mostly thiabendazole) or
      tetrahydropyrimidines (mostly pyrantel pamoate) against nematodes. We studied
      three horse stables in Rabat, one in Meknes and one in Bouznika. Two of the Rabat
      and Bouznika stables had introduced a large number of horses from countries
      (Argentina or Europe) where resistance to benzimidazoles is frequent, whereas the
      Meknes stud farm remained without foreign introduction. The number of treatments
      was not very frequent (twice a year in adult horses) but the same anthelmintics
      were used repeatedly. No resistance to dichlorvos was detected whereas
      benzimidazole and pyrantel pamoate resistances were detected for the first time
      in African horses, outside South Africa.

PMID- 16402568
TI  - Monitoring the efficacy of specific treatment in chronic Chagas disease by
      polymerase chain reaction and flow cytometry analysis.
AB  - PCR and FC-ALTA were used to monitor parasite clearance in 54 chronic chagasic
      patients who had completed therapy with allopurinol (ALLO, n = 31) or
      itraconazole (ITRA, n = 23) ten years earlier. All patients maintained positive
      conventional serology. 25 of them showed positive XD (ALLO, n = 11 and ITRA, n =
      14) and 29 negative XD (ALLO, n = 20 and ITRA, n = 9). 43 patients were positive
      by both techniques (ALLO, n = 23 and ITRA, n = 20). Seven of 54 patients were
      negative by PCR and positive by FC-ALTA and three of 54 were positive by PCR and
      negative by FC-ALTA. Only one case with both tests negative should be considered
      cured. Of 29 patients with negative XD, 14 treated ALLO (70 %) and nine with ITRA
      (77.8 %) showed positive PCR and FC-ALTA. These results do not show differences
      of efficacy among the drugs, and reinforce the relevance of using sensitive tools
      such as PCR and FC-ALTA for the follow-up of patients with chronic Chagas
      disease.

PMID- 16402569
TI  - [Faunistic note on Culcoides (Diptera, Ceratopogonidae) from the governate of
      Monastir (Tunisia)].
AB  - Following the arrival of blue-tongue in Tunisia, the authors report the results
      of the first survey made in Monastir. They show the existence of nine species of
      Culicoides, three of which are new to the country IC. paolae, C. imicola, C.
      newsteadi), that now brings to 22 the number of the known species.

PMID- 16402570
TI  - [Prevalence of Diphyllobothrium latum, L., 1758 infestation in Perca fluviatilis
      from Lake Leman].
AB  - Diphyllobothriasis is contracted by consuming raw or undercooked freshwater fish
      and is still present on the shores of lake Leman. The aim of this study was to
      evaluate the prevalence of Diphyllobothrium latum plerocercoid larvae in Perca
      fluviatilis from this lake. Four to 10% of perch fillets examined in November
      2003, February 2004, April 2004 and January 2005, were infested with D. latum
      larvae. The identification of the larvae was confirmed by PCR and sequencing of
      the 18S rDNA.

PMID- 16402571
TI  - [Ophidian envenomations and emergencies in Sub-Saharan Africa].
AB  - In West Africa, the ophidian envenomations constitute a frequent medico-surgical
      emergency that has been identified both by health officers and the patients
      themselves or their circles. Yet, their management is highly insufficient. The
      impact of this event is extremely underestimated. A compilation of recent studies
      has allowed the assessement of the annual number of snakebites at more than one
      million among which 500,000 envenomations. There would be about 20,000 deaths
      each year among which only a small part is reported by the national health
      departments. The circumstances and context of the accidents do not favor a care
      management of these cases. The bites often occur in remote countryside, far from
      dispensaries and even more from hospitals. The consultation delays are very
      important, between 4 and 48 hours. In addition, the patients are often reluctant
      to choose the therapeutic course: 50 to 90% of them are willing to consult a
      traditional practitioner first. The clinical table, in theory relatively simple,
      is not correctly analyzed by health officers: the respiratory distress after a
      cobra envenomation is only treated exceptionally by an artificial respiration
      although life-saving and haemorrhagic syndromes are only diagnosed after the
      haemorrhages externalisation. The treatment is ill-codified and still remains
      unknown by most of health officers. The antivenom, which is the only efficient
      etiologic treatment, is not available. Less than 1% of the needs are now covered
      and the treatment cost corresponds to several months of a farmer family's income.
      Three important issues prevail now in West Africa:--A more precise
      epidemiological evaluation of the envenomation accidents would help to identify
      the needs;--A better availability of drugs and particularly of antivenom would
      significantly reduce the mortality;--An appropriate training of health staff,
      particularly those working in peripheral health centres, would lead to the
      development of intensive cares. Thus, it is expected to reduce by 90% the
      mortality rate in the next ten years.

PMID- 16402572
TI  - [Methodology for household surveys: the case of two investigations carried out
      (example of Bandafassi, Senegal)].
AB  - The survey area of Bandafassi, in Eastern Senegal, was the subject of two studies
      each allowing to measure the risk of bite and death consecutive to a snakebite in
      a rural area. Two different methods were being used to carry out these
      investigations. Although both were based on the visit of households, the sample
      of the first study was designed to be representative of the population (the zone
      of study of Bandafassi is the subject of a regular demographic follow-up since
      1970) while the second study was carried out by interviewing the concession
      (groups of households) heads. Therefore, the analysis of these surveys must take
      into account the sampling discrepancies. In spite of the different methodologies,
      similarities in the results obtained validate both methods and permitted to
      explain the small variations observed and to measure bias relative to this type
      of investigations.

PMID- 16402573
TI  - [Hospital care of snakebites in Africa].
AB  - Snakebites constitute a public health problem in Africa, with some 600,000
      envenomations and 20,000 estimated deaths per year. Hospital care of cases guided
      by written protocols which take into account the epidemiological and
      physiopathological data, as well as the hospital situation, starts in the
      emergency room and is based on the diagnosis of envenomation, either by vipers or
      elapids. If this diagnosis is confirmed, intensive treatment must ensue. It
      includes a non-specific component, particularly the treatment of hypovolemia,
      consumptive coagulopathy tissue necrosis and respiratory failure and a specific
      component, immunotherapy the only ethiological treatment. The latter consists in
      giving an iv injection of polyvalent purified immunoglobulin fragments against
      the venom. This attention is included in a general public health policy which
      takes into account the organization and financing of the treatment.

PMID- 16402574
TI  - [Appraisal of snakebite incidence in Senegal, West Africa].
AB  - Surveys were carried out in four savannah areas of Senegal. The studied zones had
      different climatic, economic and demographic characteristics. Two types of
      studies were performed: on the one hand, a retrospective survey carried out in
      health centres and, on the other, household surveys in the corresponding areas;
      all households were questioned in Niakhar, but only selected households in other
      areas following WHO method of cluster survey for vaccine coverage. Questions
      involved the circumstances of the bite, symptoms and treatment. The retrospective
      survey reported very few cases of snakebites over the prospected period. In
      addition, two zones of surveys were population study areas under observation
      since more than 20 years and, it has been possible to check certain information
      in the data base. In the first zone, Thies, a sub-urban area (population density
      higher than 150 inhabitants per km2), primarily occupied by fruit plantations
      (mangos, oranges, lemons) and gardens, the annual incidence of snakebites (i.e.
      all snakebites including those without any symptoms) reached 43 bites per 100,000
      and mortality was 1.8 deaths per 100,000. In the study zone of Niakhar, located
      in the groundnut culture area of Senegal which is also highly populated (130
      inhabitants per km2), the incidence of snakebites was 23 bites per 100,000 and
      mortality was close to 1.8 deaths per 100,000 a year. The area of Nioro du Rip is
      a mixed agricultural area (food producing and revenue agriculture) and less
      populated (100 inhabitants per km2). The annual incidence was roughly of 304 per
      100,000 and the mortality 3.6 per 100,000. Finally, the fourth area, Bandafassi
      in the extreme South-East of Senegal is a mountainous zone exclusively occupied
      by bush and food producing agriculture, and sparsely populated (20 inhabitants
      per km2). The incidence was 915 per 100,000 and the mortality 11 deaths per
      100,000. The population at risk involved males from 15 to 45 years. Pastoral work
      (agriculture and breeding) was at the origin of the majority of the accidents.
      The recourse to traditional practitioners was systematic, which explained why the
      data from the health centers were not relevant enough to evaluate the importance
      of the envenoming.

PMID- 16402575
TI  - [Impact of snakebites in rural environment: community survey in the rural
      development community (DRC) of Frilguiagbe, Republic of Guinea].
AB  - An exhaustive study has been carried out in the rural development community (DRC)
      of Frilguiagbe, located at 115 km from Conakry in the Conakry-Kindia highway. It
      concerns a population of 23,442 inhabitants divided into 3,047 households. The
      survey was carried out at three levels:--community level;--health centres;-
      traditional healers. In the household survey made between 2002 and 2003, 175
      snakebites cases were recorded. In health centres, only two (2) cases were
      recorded from 1993 to 2003. On the other hand, 80% (=140) of the cases registered
      in the households have consulted a traditional healer. On the whole, there were 9
      deaths (5%). Such a result shows that the collect of information from the
      consultation registers is not appropriate to appraise the importance of
      envenomations in our country.

PMID- 16402576
TI  - [Envenomations of the Kindia prefecture treated in the Institut Pasteur of Guinea
      for one year (2003-2004)].
AB  - After a broadcast information on the availability of antivenom serum in Guinea
      Pasteur Institute (GPI), 76 snakebites victims have been admitted to the health
      centre of GPI within 11 months (October 2003-September 2004), 48 of whom were in
      a serious condition. In addition, 13 deaths occurred during the transport of the
      victims, i.e. a total incidence of 89 cases. Among these cases, 84% of the bites
      occurred during farming works (clearing, weeding, harvesting). Among the 76
      victims who came alive at GPI, 9 of them did not present any envenomation. The 67
      other victims have systematically received antivenom serum with a 100% recovery
      rate.

PMID- 16402577
TI  - [Envenomation accidents caused by snakebites in the surgical emergency unit of
      Gabriel-Toure Hospital, Bamako, Mali (1998-1999)].
AB  - This study aimed at assessing envenomations caused by snakebite in the Gabriel
      Toure hospital between January 1998 and December 1999. We included in total 112
      victims of snakebites proved by the identification of the snake, the fangs traces
      and envenomation signs. The bites concerned 34 women (30.36%) versus 78 men
      (69.64%) from the Bamako district, while 66.7% were from a rural environment. The
      farmers were the most affected category (35.1%). The bite concerned the lower
      limb in 83.3% of the cases. Snakes such as Echis ocellatus, Bitis arietans, Naja
      nigricollis and N. katiensis caused the envenomations. The viperine syndrome
      dominated the clinical picture; its severity depended on the bleeding stage and
      the delay of administration of the antivenom serum (AVS) after the envenomation:
      19 hours for Echis sp. and 2 hours for Naja sp. This study shows that the
      envenomation accidents caused by snakes are frequent with a lethality rate of
      9.8%.

PMID- 16402578
TI  - [Epidemiological aspects of snakebites in Benin].
AB  - Among rural environmental health emergencies, snakebite was common in villages
      community and agriculture activities. Their frequency and fatal complication
      depend on the venomous character of the species and the lack of early treatment.
      The aim of this work was to describe some epidemiological aspects of the
      snakebites and to suggest preventive strategies to avoid complication. So, we
      conducted a retrospective survey using health centre data of the statistic office
      of MOH from 2000 to 2002. During the three years, 10,954 cases were notified with
      an annual total average of 3,651 bites with 158 for kid's average. The wounded
      distribution indicated more wounded male than female (sex-ratio = 2:1), with a
      yearly rising trend in adults. Fatality rate was 0.94% in 2001 and rose to 1.57%
      in 2002. Fatality rate was higher in kids (1.67%) than in adults (1.08%).
      According to the ecological environment northern provinces were more exposed
      (71.6%) than central and south areas. But in central area, fatality rate was
      higher (1.05%) than in others (0.80%). Based on these findings, authors suggested
      the training of caregivers in rural health centre on earlier treatment, community
      training on snakebite primary health care and implementation of snakebite
      register

PMID- 16402579
TI  - [Dangerous scorpions from Niger].
AB  - Two dangerous scorpion species are responsible for the severe human envenomations
      in Niger, Leiurus quinquestriatus (H. et E.), the most abundant, and Androctonus
      aeneas C.L. Koch, less frequent and described in a Sahel country for the first
      time. Up to now, A. aeneas was known in North Africa only. Its venom is highly
      toxic for humans, similar to those of the most dangerous species living in
      Africa, such as L. quinquestriatus and other species belonging to the genus
      Androctonus, A. australis (L.) and A. mauretanicus (Poc.), for the envenoming
      treatment of which specific antivenoms are prepared. Taking into account the
      absence of a specific antivenom for A. aeneas, the paraspecific neutralising
      effect of these antivenoms should be tested.

PMID- 16402580
TI  - [Biogeographical distribution of snakes in Cameroon: the case of venomous
      snakes].
AB  - A preliminary analysis of the distribution of snakes captured in Cameroon between
      1999 and 2004 is presented in this study. This work helps to provide a better
      understanding of the distribution of the venomous snakes. The main focus of this
      study was to identify regions of high diversity of venomous species, a useful
      step towards developing a national strategy of snakebite care and antivenom
      distribution. We recorded 4,910 specimens of 150 species from 361 localities
      throughout Cameroon. Among the ten provinces in Cameroon, the southwest province
      recorded the highest number of venomous snakes. Diversity was less in the far
      north province, but the high abundance of Echis ocellatus seems to be responsible
      for many snake bites in the region. Of all venomous snakes, the forest cobra Naja
      melanoleuca was the most abundant in the forest region. The humid savannah region
      was dominated by Causus maculatus while the Sahelian part by Echis ocellatus.
      Given the abundance and high snake bite cases of the latter in the region,
      snakebite care from a national point of view should begin from the far-north
      towards the forest region of the south-west Cameroon.

PMID- 16402581
TI  - [Distribution of antivenoms in Cameroon].
AB  - Two snake antivenoms are distributed in Cameroon, though their availability in
      district hospitals varies. These snake antivenoms are FAV-Afrique (Aventis
      Pasteur) available at Centre Pasteur Cameroun and Polyvalent serum (Serum
      Institute of India = SII) distributed by a wholesaler (CENAME). The price remains
      a very important factor. We have noted that some district hospitals do not stock
      antivenom at all, while others stock very few and sometimes only one vial whereas
      a good management of snakebite may require up to 14 vials for some envenomations.
      However, data collected by the CAMHERP project that permit to identify high-risk
      areas of envenomation might be used as a database for the distribution of snake
      antivenom in Cameroon.

PMID- 16402582
TI  - [Situation of the envenomations by snakebites in Congo-Brazzaville:
      epidemiological, clinical and therapeutic approaches].
AB  - A retrospective study was carried out in six areas of Congo and in the town of
      Brazzaville for the period between 2000 and 2004 in order to evaluate the
      incidence, lethality, treatments and the used drugs in cases of snakebites. We
      associated a retrospective survey using health centre registers (11 centres) and
      a retrospective survey based on the staff statements of village communities (42)
      and private pharmacies and drug centrals. The questionnaire related to the
      snakebites (identification of victims, place of bite, symptoms and treatment) was
      used in communities. The total case fatality rate was relatively low (3,11%). The
      incidence of the estimated snakebites was higher in villages (221) than in health
      centres (165). But, lethality was equal in the two study clusters (6 cases versus
      6 cases). There was no difference of cases rate between male and female subjects.
      Around urban areas, many victims consulted health centre and in rural area, many
      victims resorted systematically to traditional practitioners. In drug centrals
      and private pharmacies of Brazzaville, drugs against envenomations were proposed,
      respectively, by one and two structures. In health centres these drugs were not
      available. This evaluation could be underestimated as many victims consulted
      traditional practitioners. This explains why collecting data from health centre
      registers is not sufficient to evaluate the importance of envenomations in our
      study area.

PMID- 16402583
TI  - [Epidemiology and management of snakebites in the province of Bas-Congo
      (Democratic Republic of Congo)].
AB  - A study on epidemiology and management of snakebites was performed in the
      province of Bas-Congo of the Democratic Republic of Congo. This province, located
      in the West of the RDC is divided into 31 health zones and several other
      secondary health structures. The study extended over a period going from 2000 to
      2004 and was carried out simultaneously in the households and health centres or
      hospital complex of Kavwaya, Sonabata and Kasangulu regions. Researches involved
      the circumstances of snakebites, symptoms observed and treatment chosen by the
      patients. The following results were obtained:--In the health centres and
      hospital complexes, out of a total of 293 recorded cases, mortality rose to
      10.2%.--In the surveyed households, 82 cases of snakebites were recorded with 5%
      deaths and 27% who chose traditional medicine.--The distribution of the cases
      according to age showed that the incidence of the bites was weak in childhood
      (15%); the sex ratio was reversed between the health structures and the household
      survey.

PMID- 16402584
TI  - [Preliminary results of an herpetology investigation in sugar cane plantation in
      Democratic Republic of Congo].
AB  - Out of the 3,000 species of snakes described in the world, 163 are currently
      known from D.R. of Congo. We performed a systematic survey in sugar-cane
      plantations of the Sugar Company of Kwilu-Ngongo (Bas-Congo), located at 160 km
      South-West from Kinshasa and exploiting nearly 10,000 ha. The plantation is
      divided into 3 sectors in the middle of which we deposited barrels filled of
      formaldehyde. All the employees of the Sugar Company of Kwilu-Ngongo were
      requested to collect encountered snakes and put them in the nearest barrel.
      Between August 9th and September 21st, 2004, we collected 36 snakes in two
      different sites, revealing the presence of 3 families and 12 species. The most
      abundant species in Causus maculatus (47% in the first site--Point 8--and 29% in
      the second site--Point 13). The most poisonous and dangerous species were
      captured only in the first site--point 8, and were Dendroaspis jamesoni and Naja
      melanoleuca, both young.

PMID- 16402585
TI  - [Epidemiology of snakebites in sugar cane plantations of Kwilu Ngongo in
      Democratic Republic of Congo].
AB  - An epidemiological study was undertaken in a sugar cane plantation of the Sugar
      Company of Kwilu Ngongo in the Democratic Republic of Congo (DRC) to evaluate the
      incidence of the snakebites, to report the epidemiological and clinical
      indicators and the therapeutic practices. The plantations extend by 41 km
      covering about 10,000 hectares in arboreal savannahs. The method associated i) a
      retrospective survey carried out from the registers of two health centres located
      in the heart of the plantations, then in the files of the central hospital of the
      sugar company and in a public health centre, and ii) an household survey using a
      questionnaire administered to 579 concessions and households over six years. The
      calculated incidence is estimated at 80 bites per annum for 100,000 inhabitants.
      More than half of the bites involved men working in industrial sugar cane
      plantations or in the fields and occurred during the rain season. Setting fire in
      sugar cane plantations during harvest had an influence both on the snake
      behaviour and men's activities. Because of the lack of antivenom, the treatment
      of snakebites remained symptomatic. The average duration of hospitalizations was
      4 days, the criterion of monitoring being based on the disappearance of the
      oedema localized at the foot sometimes extending to the leg.

PMID- 16402586
TI  - Round table of November 20th, 2004: recommendations for improving the management
      of envenomations.
AB  - The round table underlines the necessity to follow the epidemiological and
      clinical surveys in order to precise the incidence and severity of snakebites and
      inform the health authorities that could thus arrange to take in charge
      envenomation accidents. Simple therapeutic protocols adapted to epidemiological
      and clinical data will be elaborated according to each level of health pyramid.
      They will be included in the health staff training and integrate traditional
      practitioners whose role must be clearly defined. An experimental and clinical
      validation must confirm its appropriateness with countries and victims needs.
      Some microeconomic surveys are necessary to identify adapted funding and thus
      improve their accessibility

PMID- 16402587
TI  - Genetic data concerning the problem of differentiation of Northern Mongoloids,
      American Indians and Caucasoids in the northern territory of Eurasia.
AB  - Basing on the frequencies of 28 alleles of 12 polymorphic loci of blood groups,
      serum proteins and red cell enzymes the matrix of genetic distances between 11
      populations of Europe, Asia and America was calculated. This matrix and the
      dendrogram based on it permitted to suggest that the region of South Siberia and
      the neighbouring regions of Central Asia was the place, where the paleolithic
      populations were divided into the ancestors of the Northern Mongoloids,
      Caucasoids and American Indians. The published data concerning the human mtDNA
      polymorphisms support the hypothesis of the author.

PMID- 16402588
TI  - Asymmetry and diversity of dermatoglyphic traits: population comparison in five
      endogamous groups of West Bengal, India.
AB  - Five different endogamous populations encompassing the main social ranks in the
      caste hierarchy of West Bengal, India were analyzed. To compare variability in
      populations with contrasting ethnohistorical backgrounds, analysis of variance,
      Scheffe's test and cluster analysis were performed, as based on dermatoglyphic
      variables, namely, 22 quantitative traits and 36 indices of diversity and
      asymmetry. The present study reveals that: 1. Overall disparities among the 5
      populations are expressed only in finger ridge counts on the Ist and Vth digits
      and PII, in a-b ridge counts, in endings of main lines A and D, and in MLI on the
      palms; 2. Heterogeneity is greater in fluctuating asymmetry than in directional
      asymmetry; 3. There is a greater heterogeneity in the 22 quantitative traits than
      in the 36 indices of diversity and asymmetry, with females contributing more than
      the males; 4. The highest contribution to population variation is by Lodha among
      five populations; 5. Inter-group variations are homogeneous in most of the
      variables, which does not correspond with the relationships to caste hierarchy of
      these populations; 6. The dendrograms based on dermatoglyphic variables
      demonstrate that the traditional grouping of Indian populations, based on caste
      hierarchy, may not be a reflection of their genetic origin, in that the pattern
      of clustering corresponded best with the known ethnohistorical records of the
      studied populations; 7. Hence, dermatoglyphic affinities may prove quite useful
      in tracing the ethnohistorical background of populations.

PMID- 16402589
TI  - Dermatoglyphic studies in eastern and south-eastern Europe.
AB  - In nine population samples from Bulgaria, Croatia, Greece, Hungary, Republic of
      Macedonia (Skopje and Aromuns from Stip region), Romania, Serbia and Slovakia 12
      dermatoglyphic variables have been studied. There are distinct differences
      between the populations and between males and females. The Macedonian Aromuns are
      clearly separated from the other populations.

PMID- 16402590
TI  - Identification of family relationships by epigenetic traits.
AB  - In analyzing family burials, it is often necessary to establish the nature of the
      family relationship. This study examines 18 skulls from the 14th and 15th
      century, presumptively assigned to the family of the Counts of Celje from the
      territory of present-day Slovenia. Though DNA analysis is the identification
      method of choice, it is not always possible to apply it. In our case we were
      unable to isolate the genetic material and had to use classical identification
      methods. After determining sex and age, we established the kinship by comparison
      of X-ray images of paranasal cavities (frontal and maxillary sinuses, and also
      orbital and nasal cavities), the shape and size of which are autosomal dominant
      inherited characters. The comparison also extends to numerous other likewise
      inherited epigenetic trait similarities on the skulls. We identified all skulls,
      compared them with historical and genealogical data, grouped them into nuclear
      families--one of them is presented in this article-, and proved that they belong
      to the assigned family. This multidisciplinary work, based on latest epigenetic
      research, is highly relevant for modern non-genetic identification studies and
      verification of kinship by skulls collectively interred and can be applied in
      similar cases where isolation of DNA is no longer possible, even though the
      skeletal remains may not be old.

PMID- 16402591
TI  - Taxonomic revision of Central Mexican mammoths in Paleoindian sites.
AB  - Central Mexican mammoth species taxonomy has been based on the quotient Molar
      length/Number of dental plates, which sorted three species, Mammuthus imperator,
      columbi and ?jeffersonii. New evidence from skull morphology sorts only two
      subspecies, M. columbi columbi and M. columbi felicis as being present during
      Paleoindian time.

PMID- 16402592
TI  - [Sports-anthropological analysis of Tunisian elite karateka].
AB  - This study is based on a careful sport anthropological investigation (ca. 15 min)
      of 25 Tunisian athletes of the Karate team (aged 18 - 31 years) with special
      permission of the Tunisian Ministry of Youth and Sports. Considering the height
      of the Tunisian elite athletes (175.6 +/- 4.9 cm), heavier kareteka are bigger
      (178.9 +/- 2.2 cm vs. 171.4 +/- 3.9 cm). The mean weight was 73.1 +/- 8.2 kg
      (heavier athletes 78.7 +/- 5.9 kg vs. lighter athletes 66.0 +/- 4.1 kg). On
      Conrad's chessboard diagram all the Tunisian karateka were placed in the
      leptomorph half, only two in the metromorph corridor, but most of them in the
      middle between hypoplastic and hyperplastic poles. The AKS index diagram
      demonstrates a faint diagonal positioning of the single weight categories, with
      progression of body mass from the lower to the upper right area. None of the
      athletes surpasses a body height of 184 cm. The variation of the AKS index is
      higher than the variation of body height. The constitutional analysis according
      to Knussmann (1961) reveals an orientation of heavier weight classes towards
      macrosomia and pyknomorphism. The proportional figures of the athletes show a
      small variation of joint heights in lower extremities. In Parnell's somatochart
      (1954, 1958) the concentration of Tunisian karateka is found in the mesoectomorph
      third as well as in the somatochart of Heath & Carter (1967). Further sport
      anthropological karate studies should focus on adolescents and females as well as
      on physiological and biomechanic parameters.

PMID- 16402593
TI  - Gender differences in fat patterning in children living in Ankara.
AB  - Body composition is an excellent indicator for assessing obesity and nutritional
      status of both individuals and populations. Youth obesity has important health
      and social implications, because a large proportion of adult obesity has its
      origin in childhood. Numerous studies report that adverse levels of
      cardiovascular diseases risk factors are associated with adiposity in children.
      Concerning the Turkish population there is up to now only limited information
      with regard to adiposity in children. The aim of this study was therefore to
      determine the anthropometric and body composition characteristics and to
      investigate sex differences in fat patterning including fat distribution in a
      group of children living in Ankara. The present study evaluated the body
      composition of 332 boys and 269 girls aged between 8 and 11 years, attending
      public schools. It was carried out by a cross-sectional study and was focused on
      that anthropometric variables, which reflect body fat and fat-free mass.
      Anthropometric measurements including height, weight, triceps and subscapular
      skinfolds thickness were carried out on these children. The body mass index (BMI)
      was also calculated. The measurements were used to estimate the two-compartment
      model of body composition: fat-free mass (FFM) and body fat (BF) from skinfold
      equations. The mean fat percentage in boys is highest at 11 years (16.8%) and
      lowest at 10 years (15.6%). In girls these figures come to 18.2% and 17.1%,
      respectively. Girls of these age groups have a significantly larger percentage of
      body fat and skinfold thickness. At this young age there is therefore clear
      evidence of sexual dimorphism in fat patterning, as girls are showing a greater
      subcutaneous adiposity, which is mainly contributed by the triceps fat. The body
      fat (kg) increases in both sexes all over the investigated age groups. The
      Pearson correlation matrix showed a high significant relation between the
      anthropometric measurements (p < 0.01). The present study confirms the findings
      that sexual dimorphism of fat patterning in children is to be seen in the age of
      8 - 11 years. It furthermore presents basic data of body composition, which could
      serve as reference data in other studies on the Turkish population.

PMID- 16402594
TI  - Age trends in anthropometric characteristics among 6-9 years old Bengalee Hindu
      school girls of Kolkata, India.
AB  - A cross-sectional study of 431 6-9 years old urban Bengalee Hindu schoolgirls of
      Kolkata, India, was undertaken to study age trends in anthropometric
      characteristics including regional and subcutaneous adiposity. The anthropometric
      variables measured included height, weight, sitting height (SH), waist (WC), hip
      (HPC), thigh (TC), mid-upper arm (MUAC) and medial calf (MC) circumferences as
      well as triceps (TSF), biceps (BSF), subscapular SUBSF), suprailliac (SUPSF) and
      medial calf (MCASF) skinfolds. The results revealed, that there was a significant
      increasing age trend for all the anthropometric variables including the two
      derived variables: body mass index (BMI) and subischial leg length (SLL). For all
      variables, the lowest and the highest means were observed at the age of 6 and 9
      years, respectively. The maximum increase in weight, BMI, all linear
      measurements, WC and HPC were observed during the period 6-7 years of age. In
      general, all skinfolds recorded similar yearly increments. More importantly, this
      study clearly indicated that among Bengalee girls aged 6-9 years, the highest
      amount of linear growth (height, SH and SLL) was observed at 6 years of age. The
      overall adiposity (BMI) also recorded the maximum increment during this period.
      The unique data presented here can be used as reference values for urban Bengalee
      Hindu girls aged 6-9 years.

PMID- 16402595
TI  - Effect of skill on work productivity and physical body dimensions of the Oraon
      tea garden labourers of the Jalpaiguri district, West Bengal, India.
AB  - Skill is one of the factors influencing labour productivity of manual labour. The
      present study aims to find out the possible relationship between skill and
      productivity and between skill and physical body dimension among the tea garden
      labourers of Northern West Bengal, India. Skill was measured by indigenously
      devised test protocols developed only for this purpose. Productivity or labour
      output was measured in terms of amount of tea leaves (in weight) plucked in a day
      by an individual. Physical body dimension was recorded in terms of a list of
      anthropometric traits. The results show an inconsistent relationship between
      skill and productive output and a non-significant relationship between skill and
      physical body dimensions. However, there are some trends that skill is high in
      younger individuals and low skill in females is associated with relatively high
      fat accumulation in the body.

PMID- 16402596
TI  - RTOG study shows improved survival for prostate cancer patients given adjuvant
      goserelin.

PMID- 16402597
TI  - Analysis of heartbeat dynamics by point process adaptive filtering.
AB  - Heartbeats are a point process yet, most of the current analysis methods do not
      model this important characteristic of these data. We describe human heartbeat
      time series as a history dependent inverse Gaussian model. We present a point
      process adaptive filter algorithm to estimate the model's time-varying
      parameters, and use it to compute new measures of heart rate variability. We
      apply our algorithm to analyze simulated heartbeat data and actual heartbeat data
      from a tilt table experiment and from healthy subjects and subjects with
      congestive heart failure during sleep. Our results suggest a new approach for
      characterizing heartbeat dynamics.

PMID- 16402598
TI  - An efficient method for handling ectopic beats using the heart timing signal.
AB  - The problem of analyzing heart rate variability in the presence of ectopic beats
      is revisited. Based on the integral pulse frequency modulation model and the
      closely related heart timing signal, a new technique is introduced which corrects
      for the occasional presence of ectopic beats. The correction technique, which
      involves the occurrence times of a certain number of beats preceding the ectopic
      beat, is computationally very efficient. From actual heart rate data, the results
      show that the new technique is associated with a much lower computational
      complexity (flops reduced by a factor of about 3000) than the original heart
      timing technique, while producing similar performance. It is also shown that the
      power spectrum and related clinical indices obtained by the new technique are
      more accurately estimated than by other methods.

PMID- 16402599
TI  - Renyi entropy measures of heart rate Gaussianity.
AB  - Sample entropy and approximate entropy are measures that have been successfully
      utilized to study the deterministic dynamics of heart rate (HR). A complementary
      stochastic point of view and a heuristic argument using the Central Limit Theorem
      suggests that the Gaussianity of HR is a complementary measure of the
      physiological complexity of the underlying signal transduction processes. Renyi
      entropy (or q-entropy) is a widely used measure of Gaussianity in many
      applications. Particularly important members of this family are differential (or
      Shannon) entropy (q = 1) and quadratic entropy (q = 2). We introduce the concepts
      of differential and conditional Renyi entropy rate and, in conjunction with
      Burg's theorem, develop a measure of the Gaussianity of a linear random process.
      Robust algorithms for estimating these quantities are presented along with
      estimates of their standard errors.

PMID- 16402600
TI  - Unique very low-frequency heart rate variability during deep sleep in humans.
AB  - We investigate heart rate variability (HRV) in the very low-frequency (VLF) range
      (0.003-0.04 Hz) during deep sleep in good sleepers. Spectral analysis of HRV
      during deep sleep reveals consistent peaks at <0.04 Hz. By using wavelet
      analysis, we find both stationary and nonstationary periodic patterns in the VLF
      range, the presence of which has been discussed but has not been fully
      established to date. Although the mechanism(s) behind the unique VLF oscillations
      remain to be fully explored, we conjecture that there is an endogenous rhythmic
      component in human HRV in the VLF range. Further, our results also suggest a need
      for caution in the interpretation of the VLF spectral power in HRV during deep
      sleep.

PMID- 16402601
TI  - Individual time-dependent spectral boundaries for improved accuracy in time
      frequency analysis of heart rate variability.
AB  - Heart rate variability (HRV) is a major noninvasive technique for evaluating the
      autonomic nervous system (ANS). Use of time-frequency approach to analyze HRV
      allows investigating the ANS behavior from the power integrals, as a function of
      time, in both steady-state and non steady-state. Power integrals are examined
      mainly in the low-frequency and the high-frequency bands. Traditionally, constant
      boundaries are chosen to determine the frequency bands of interest. However,
      these ranges are individual, and can be strongly affected by physiologic
      conditions (body position, breathing frequency). In order to determine the
      dynamic boundaries of the frequency bands more accurately, especially during
      autonomic challenges, we developed an algorithm for the detection of individual
      time-dependent spectral boundaries (ITSB). The ITSB was tested on recordings from
      a series of standard autonomic maneuvers with rest periods between them, and the
      response to stand was compared to the known physiological response. A major
      advantage of the ITSB is the ability to reliably define the mid-frequency range,
      which provides the potential to investigate the physiologic importance of this
      range.

PMID- 16402602
TI  - Assessment of the autonomic control of heart rate variability in healthy and
      spinal-cord injured subjects: contribution of different complexity-based
      estimators.
AB  - We investigated how complexity-based estimators of heart rate variability can
      detect changes in cardiovascular autonomic drive with respect to traditional
      measures of variability. This was done by analyzing healthy subjects and
      paraplegic patients with different autonomic impairment due to low (vascular
      impairment only) or high (cardiac and vascular impairment) spinal cord injury,
      during progressive autonomic activations. While traditional techniques only
      quantified the effects of the autonomic activation, not distinguishing the
      effects of the lesion level, some recently proposed complexity estimators could
      also reveal the pathologic alterations in the autonomic control of heart rate.
      These estimators included the detrended fluctuation analysis coefficient
      (sensitive to both low and high autonomic lesions), sample entropy (sensitive to
      low-level lesions) and the largest Lyapunov exponent (sensitive to high-level
      lesions). Thus complexity-based methods provide information on the autonomic
      function from the heart rate dynamics that cannot be obtained by traditional
      techniques. This finding supports the combined use of both complexity-based and
      traditional methods to investigate the autonomic cardiovascular control from a
      more comprehensive perspective.

PMID- 16402603
TI  - Coupling arterial windkessel with peripheral vasomotion: modeling the effects on
      low-frequency oscillations.
AB  - Arterial pressure (AP) and heart rate (HR) waves have long been recognized as an
      important sign of cardiovascular regulation, however, the underlying interactions
      involving vasomotion, arterial mechanisms and neural regulation have not been
      clarified. With the aid of simple dynamical models consisting of active
      peripheral vascular districts (PVDs) fed by a compliant/resistant arterial tree,
      the relationship between local AP and flow and systemic AP waves were analyzed. A
      PVD was described as a nonlinear flow regulation loop. Various feedback dynamics
      were experimented and general properties were focused. The PVDs displayed a
      region of active flow compensation against pressure changes, in which self
      sustained low-frequency (LF, 0.1 Hz) appeared. Oscillations critically depended
      on parameter, Teq, analogous to a windkessel time constant, proportional to
      arterial compliances: a value of about 2 s (consistent with a normal pulse
      pressure) performed a buffering effect essential for LF oscillations in
      peripheral flow; conversely, stiffer arteries damped LF vasomotion. Two PVDs fed
      by a common compliance oscillated in phase opposition; the consequent negative
      interference cancelled systemic AP waves, even in presence of large peripheral
      oscillations. The partial disruption of phase opposition by a common neural drive
      oscillating at a LF proximal to that of the PVDs unveiled LF waves in AP. Also,
      several PVDs with randomly different natural frequencies displayed a tendency to
      reciprocal cancellation, while a limited neurally induced phase alignment
      unmasked LF oscillations at systemic level. It is concluded that vasomotion,
      arterial compliances and, neural drives are all elements which may cooperate in
      forming AP waves.

PMID- 16402604
TI  - Causal cross-spectral analysis of heart rate and blood pressure variability for
      describing the impairment of the cardiovascular control in neurally mediated
      syncope.
AB  - A causal approach to the calculation of coherence and transfer function between
      systolic pressure (SP) and RR interval variability was applied in eight patients
      and eight control subjects during prolonged tilt test for investigating the
      impairment of cardiovascular control related to neurally mediated syncope. The
      causal analysis showed a depressed baroreflex regulation in resting patients,
      with reduced gain and increased latency from SP to RR, and a drop of the
      baroreflex coupling immediately before syncope. These findings, which were not
      elicited by traditional cross-spectral analysis, strongly suggest the use of the
      causal approach for the study of syncope mechanisms.

PMID- 16402605
TI  - Autonomic cardiovascular control following transient arousal from sleep: a time
      varying closed-loop model.
AB  - Recent studies suggest that exposure to repetitive episodes of hypoxia and
      transient arousal can lead to increased risk for cardiovascular disease in
      patients with obstructive sleep apnea syndrome (OSAS). To obtain an improved
      understanding of and to quantitatively characterize the autonomic effects of
      arousal from sleep, a time-varying closed-loop model was used to determine the
      interrelationships among respiration, heart rate and blood pressure in 8 normal
      adults. A recursive least squares algorithm was used in combination with the
      Laguerre expansion technique to estimate the time-varying impulse responses of
      the 4 model components. We found that during arousal: 1) respiratory-cardiac
      coupling gain increases in nonrapid-eye movement (NREM) but not in REM sleep; 2)
      in both NREM and REM sleep, baroreflex gain shows an initial increase, but this
      is followed by a more sustained decrease below pre-arousal baseline levels,
      allowing sympathetic tone to be elevated over a relatively long duration; 3) the
      gains of other model components show increases with arousal that are consistent
      with the increased sympathetic modulation of systemic vascular resistance and
      contractility of the heart. These findings establish a normative database against
      which further measurements of cardiovascular arousal responses in OSAS may be
      compared.

PMID- 16402606
TI  - Local holder exponent analysis of heart rate variability in preterm infants.
AB  - Heart rate variability (HRV) displays scale-invariant fractal properties. Recent
      studies have revealed multifractal properties in the healthy human HRV, which
      could be characterized by singularities with various strength of local Holder
      exponents embedded in HRV. In this paper, HRV time series from preterm infants,
      whose autonomic nervous system undergoes dramatic development, were collected
      longitudinally. Changes in fractality/multifractality of those HRV time series as
      the postmenstrual age were examined in order to see if they could quantify
      development of the autonomic nervous system. Temporal structure of the
      singularities at several representative time scales was also analyzed to show
      that intersingular event intervals could be well described by "power law
      distribution," and the singular events appeared with age-dependent long-range
      correlation in its strength. Detailed analyses suggested that fractality and
      multifractality of HRV, respectively, could quantify the development of the
      respiratory center and the parasympathetic nervous system in the preterm infants.
      The results obtained in this study might be beneficial for detecting occurrences
      of life threatening singular events such as big apnea in preterm infants.

PMID- 16402607
TI  - Aging of complex heart rate dynamics.
AB  - We reveal unexpected origins of age induced departure from 1/f-type temporal
      scaling in healthy human heart rate. Contrary to the widely established view, we
      provide evidence that age induced dynamical imbalance in the autonomic control is
      not due to the emergent functional dominance of the sympathetic nervous system
      (SNS), but due to emerging (age dependent) relative dynamic dominance of the
      parasympathetic nervous system function. In particular, we demonstrate that the
      age induced alterations of healthy heart rate dynamics asymptotically resemble
      those in so-called primary autonomic failure with neurogenic SNS dysfunction and
      in other neurodegenerative disorders, including Parkinson's disease even without
      known autonomic abnormalities. Based upon this, we propose a novel picture of
      "autonomic aging," characterized by an insufficiency of the SNS function to cope
      dynamically with various environmental stimuli.

PMID- 16402608
TI  - Multiscale probability density function analysis: non-Gaussian and scale
      invariant fluctuations of healthy human heart rate.
AB  - For a detailed characterization of intermittency and non-Gaussianity of human
      heart rate, we introduce an analysis method to investigate the deformation
      process of the probability density function (PDF) of detrended increments when
      going from fine to coarse scales. To characterize the scale dependence of the
      multiscale PDF, we use two methods: 1) calculation of Kullback-Leibler relative
      entropy; 2) parameter estimation based on Castaing's equation (B. Castaing et al,
      1990). We compare scale-dependence of the increment PDFs between actual heart
      rate fluctuations and artificially generated Gaussian and non-Gaussian noise,
      including a widely used autoregressive model and a recently proposed multifractal
      model based on a random cascade process. Our analysis highlights an essential
      difference between heart rate fluctuations and those generated by other models.
      The outstanding feature of human heart rate is the robust scale-invariance of the
      non-Gaussian PDF, which is preserved not only in a quiescent condition, but also
      in a dynamic state during waking hours, in which the mean level of heart rate is
      dramatically changing. Our results strongly suggest the need for revising
      existing models of heart rate variability to incorporate the scale-invariance in
      the PDF.

PMID- 16402609
TI  - HRV scaling exponent identifies postinfarction patients who might benefit from
      prophylactic treatment with amiodarone.
AB  - Analysing the Holter recordings collected at baseline during the European
      Myocardial Infarction Amiodarone Trial (EMIAT), we evaluate the possibility of
      using alpha, the slope of the power spectrum of heart rate variability signals
      (HRV) in the vicinity of f = 0, for postinfarction risk stratification. We found
      no relevant difference in the values of alpha for the placebo population. On the
      contrary, in the amiodarone arm, the distinction in the survival rates of those
      with high or low alpha-values was highly significant. Moreover, high risk
      patients with respect to alpha (higher values) did not seem to benefit from
      amiodarone. The results suggest that alpha might convey physiologic information
      that is different than what is expressed by other HRV characteristics, such as
      the triangular index. When combining high risk patients in term of triangular
      index (<20) and low risk patients with respect to alpha (<median), the difference
      in survival on placebo and amiodarone became very substantial (24.2% mortality on
      placebo, 8.7% on amiodarone, p = 0.017). This might offer a possibility of
      selecting patients likely to benefit from a prophylactic antiarrhythmic treatment
      after acute myocardial infarction.

PMID- 16402610
TI  - Toward quantitative fetal heart rate monitoring.
AB  - Continuous electronic fetal heart rate (FHR) monitoring during labor is motivated
      by the clinical experience that fetal distress causes loss of FHR variation and
      the occurrence of decelerations late during uterine contraction. This practice is
      of uncertain clinical benefit, perhaps because the interpretation is qualitative.
      We have developed new quantitative measures and analyzed cardiotocograph records
      from 148 consecutive patients, 44 of whom had at least one "nonreassuring" epoch.
      In multivariate regression models, measures of deceleration and variability were
      significantly associated with the obstetrician's diagnosis (receiver operating
      characteristic area 0.84, p < 0.05). This approach may be useful clinically.

PMID- 16402611
TI  - Comparison of entropy-based regularity estimators: application to the fetal heart
      rate signal for the identification of fetal distress.
AB  - This paper considers the multiscale entropy (MSE) approach for estimating the
      regularity of time series at different scales. Sample entropy (SampEn) and
      approximate entropy (ApEn) are evaluated in MSE analysis on simulated data to
      enhance the main features of both estimators. We applied the approximate entropy
      and the sample entropy estimators to fetal heart rate signals on both single and
      multiple scales for an early identification of fetal sufferance antepartum. Our
      results show that the ApEn index significantly distinguishes suffering from
      normal fetuses between the 30th and the 35th week of gestation. Furthermore, our
      data shows that the MSE entropy values are reliable indicators of the fetal
      distress associated with the presence of a pathological condition at birth.

PMID- 16402612
TI  - Heart rate characteristics monitoring for neonatal sepsis.
AB  - While heart rate variability has been measured in many clinical settings and has
      offered insights into how HR is controlled, rarely has it offered unique
      information that has led to changes in patient management. We review our
      experience in developing continuous HR characteristics monitoring to aid in the
      early diagnosis of sepsis in premature infants in the neonatal intensive care
      unit. A predictive algorithm, developed at one center and validated at another,
      has led to diagnosis and treatment of this subacute and potentially catastrophic
      illness prior to appearance of symptoms of severe illness.

PMID- 16402613
TI  - Heart rate variability characterization in daily physical activities using
      wavelet analysis and multilayer fuzzy activity clustering.
AB  - A portable data recorder was developed to parallel measure the electrocardiogram
      and body accelerations. A multilayer fuzzy clustering algorithm was proposed to
      classify the physical activity based on body accelerations. Discrete wavelet
      transform was incorporated to retrieve time-varying characteristics of heart rate
      variability under different physical activities. Nine healthy subjects were
      included to investigate activity-related heart rate variability during 24 h. The
      results showed that the heartbeat fluctuations in high frequencies were the
      greatest during lying and the smallest during standing. Moreover, very-low
      frequency heartbeat fluctuations during low activity level (lying) were greater
      than during high activity level (nonlying).

PMID- 16402614
TI  - Hidden Markov models based on symbolic dynamics for statistical modeling of
      cardiovascular control in hypertensive pregnancy disorders.
AB  - Discrete hidden Markov models (HMMs) were applied to classify pregnancy
      disorders. The observation sequence was generated by transforming RR and systolic
      blood pressure time series using symbolic dynamics. Time series were recorded
      from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41
      controls beyond 30th gestational week. HMMs with five to ten hidden states were
      found to be sufficient to characterize different blood pressure variability,
      whereas significant classification in RR-based HMMs was found using fifteen
      hidden states. Pregnancy disorders preeclampsia and pregnancy induced
      hypertension revealed different patho-physiological autonomous regulation
      supposing different etiology of both disorders.

PMID- 16402615
TI  - Performance evaluation of fingerprint verification systems.
AB  - This paper is concerned with the performance evaluation of fingerprint
      verification systems. After an initial classification of biometric testing
      initiatives, we explore both the theoretical and practical issues related to
      performance evaluation by presenting the outcome of the recent Fingerprint
      Verification Competition (FVC2004). FVC2004 was organized by the authors of this
      work for the purpose of assessing the state-of-the-art in this challenging
      pattern recognition application and making available a new common benchmark for
      an unambiguous comparison of fingerprint-based biometric systems. FVC2004 is an
      independent, strongly supervised evaluation performed at the evaluators' site on
      evaluators' hardware. This allowed the test to be completely controlled and the
      computation times of different algorithms to be fairly compared. The experience
      and feedback received from previous, similar competitions (FVC2000 and FVC2002)
      allowed us to improve the organization and methodology of FVC2004 and to capture
      the attention of a significantly higher number of academic and commercial
      organizations (67 algorithms were submitted for FVC2004). A new, "Light"
      competition category was included to estimate the loss of matching performance
      caused by imposing computational constraints. This paper discusses data
      collection and testing protocols, and includes a detailed analysis of the
      results. We introduce a simple but effective method for comparing algorithms at
      the score level, allowing us to isolate difficult cases (images) and to study
      error correlations and algorithm "fusion." The huge amount of information
      obtained, including a structured classification of the submitted algorithms on
      the basis of their features, makes it possible to better understand how current
      fingerprint recognition systems work and to delineate useful research directions
      for the future.

PMID- 16402616
TI  - Fingerprint warping using ridge curve correspondences.
AB  - The performance of a fingerprint matching system is affected by the nonlinear
      deformation introduced in the fingerprint impression during image acquisition.
      This nonlinear deformation causes fingerprint features such as minutiae points
      and ridge curves to be distorted in a complex manner. A technique is presented to
      estimate the nonlinear distortion in fingerprint pairs based on ridge curve
      correspondences. The nonlinear distortion, represented using the thin-plate
      spline (TPS) function, aids in the estimation of an "average" deformation model
      for a specific finger when several impressions of that finger are available. The
      estimated average deformation is then utilized to distort the template
      fingerprint prior to matching it with an input fingerprint. The proposed
      deformation model based on ridge curves leads to a better alignment of two
      fingerprint images compared to a deformation model based on minutiae patterns. An
      index of deformation is proposed for selecting the "optimal" deformation model
      arising from multiple impressions associated with a finger. Results based on
      experimental data consisting of 1,600 fingerprints corresponding to 50 different
      fingers collected over a period of two weeks show that incorporating the proposed
      deformation model results in an improvement in the matching performance.

PMID- 16402617
TI  - Matching 2.5D face scans to 3D models.
AB  - The performance of face recognition systems that use two-dimensional images
      depends on factors such as lighting and subject's pose. We are developing a face
      recognition system that utilizes three-dimensional shape information to make the
      system more robust to arbitrary pose and lighting. For each subject, a 3D face
      model is constructed by integrating several 2.5D face scans which are captured
      from different views. 2.5D is a simplified 3D (x, y, z) surface representation
      that contains at most one depth value (z direction) for every point in the (x, y)
      plane. Two different modalities provided by the facial scan, namely, shape and
      texture, are utilized and integrated for face matching. The recognition engine
      consists of two components, surface matching and appearance-based matching. The
      surface matching component is based on a modified Iterative Closest Point (ICP)
      algorithm. The candidate list from the gallery used for appearance matching is
      dynamically generated based on the output of the surface matching component,
      which reduces the complexity of the appearance-based matching stage. Three
      dimensional models in the gallery are used to synthesize new appearance samples
      with pose and illumination variations and the synthesized face images are used in
      discriminant subspace analysis. The weighted sum rule is applied to combine the
      scores given by the two matching components. Experimental results are given for
      matching a database of 200 3D face models with 598 2.5D independent test scans
      acquired under different pose and some lighting and expression changes. These
      results show the feasibility of the proposed matching scheme.

PMID- 16402618
TI  - Recovering 3D human pose from monocular images.
AB  - We describe a learning-based method for recovering 3D human body pose from single
      images and monocular image sequences. Our approach requires neither an explicit
      body model nor prior labeling of body parts in the image. Instead, it recovers
      pose by direct nonlinear regression against shape descriptor vectors extracted
      automatically from image silhouettes. For robustness against local silhouette
      segmentation errors, silhouette shape is encoded by histogram-of-shape-contexts
      descriptors. We evaluate several different regression methods: ridge regression,
      Relevance Vector Machine (RVM) regression, and Support Vector Machine (SVM)
      regression over both linear and kernel bases. The RVMs provide much sparser
      regressors without compromising performance, and kernel bases give a small but
      worthwhile improvement in performance. The loss of depth and limb labeling
      information often makes the recovery of 3D pose from single silhouettes
      ambiguous. To handle this, the method is embedded in a novel regressive tracking
      framework, using dynamics from the previous state estimate together with a
      learned regression value to disambiguate the pose. We show that the resulting
      system tracks long sequences stably. For realism and good generalization over a
      wide range of viewpoints, we train the regressors on images resynthesized from
      real human motion capture data. The method is demonstrated for several
      representations of full body pose, both quantitatively on independent but similar
      test data and qualitatively on real image sequences. Mean angular errors of 4-6
      degrees are obtained for a variety of walking motions.

PMID- 16402619
TI  - On the removal of shadows from images.
AB  - This paper is concerned with the derivation of a progression of shadow-free image
      representations. First, we show that adopting certain assumptions about lights
      and cameras leads to a 1D, gray-scale image representation which is illuminant
      invariant at each image pixel. We show that as a consequence, images represented
      in this form are shadow-free. We then extend this 1D representation to an
      equivalent 2D, chromaticity representation. We show that in this 2D
      representation, it is possible to relight all the image pixels in the same way,
      effectively deriving a 2D image representation which is additionally shadow-free.
      Finally, we show how to recover a 3D, full color shadow-free image representation
      by first (with the help of the 2D representation) identifying shadow edges. We
      then remove shadow edges from the edge-map of the original image by edge in
      painting and we propose a method to reintegrate this thresholded edge map, thus
      deriving the sought-after 3D shadow-free image.

PMID- 16402620
TI  - Multisurface proximal support vector machine classification via generalized
      eigenvalues.
AB  - A new approach to support vector machine (SVM) classification is proposed wherein
      each of two data sets are proximal to one of two distinct planes that are not
      parallel to each other. Each plane is generated such that it is closest to one of
      the two data sets and as far as possible from the other data set. Each of the two
      nonparallel proximal planes is obtained by a single MATLAB command as the
      eigenvector corresponding to a smallest eigenvalue of a generalized eigenvalue
      problem. Classification by proximity to two distinct nonlinear surfaces generated
      by a nonlinear kernel also leads to two simple generalized eigenvalue problems.
      The effectiveness of the proposed method is demonstrated by tests on simple
      examples as well as on a number of public data sets. These examples show the
      advantages of the proposed approach in both computation time and test set
      correctness.

PMID- 16402621
TI  - Symbolic signatures for deformable shapes.
AB  - Recognizing classes of objects from their shape is an unsolved problem in machine
      vision that entails the ability of a computer system to represent and generalize
      complex geometrical information on the basis of a finite amount of prior data. A
      practical approach to this problem is particularly difficult to implement, not
      only because the shape variability of relevant object classes is generally large,
      but also because standard sensing devices used to capture the real world only
      provide a partial view of a scene, so there is partial information pertaining to
      the objects of interest. In this work, we develop an algorithmic framework for
      recognizing classes of deformable shapes from range data. The basic idea of our
      component-based approach is to generalize existing surface representations that
      have proven effective in recognizing specific 3D objects to the problem of object
      classes using our newly introduced symbolic-signature representation that is
      robust to deformations, as opposed to a numeric representation that is often tied
      to a specific shape. Based on this approach, we present a system that is capable
      of recognizing and classifying a variety of object shape classes from range data.
      We demonstrate our system in a series of large-scale experiments that were
      motivated by specific applications in scene analysis and medical diagnosis.

PMID- 16402622
TI  - Multibody grouping by inference of multiple subspaces from high-dimensional data
      using oriented-frames.
AB  - Recently, subspace constraints have been widely exploited in many computer vision
      problems such as multibody grouping. Under linear projection models, feature
      points associated with multiple bodies reside in multiple subspaces. Most
      existing factorization-based algorithms can segment objects undergoing
      independent motions. However, intersections among the correlated motion subspaces
      will lead most previous factorization-based algorithms to erroneous segmentation.
      To overcome this limitation, in this paper, we formulate the problem of multibody
      grouping as inference of multiple subspaces from a high-dimensional data space. A
      novel and robust algorithm is proposed to capture the configuration of the
      multiple subspace structure and to find the segmentation of objects by clustering
      the feature points into these inferred subspaces, no matter whether they are
      independent or correlated. In the proposed method, an Oriented-Frame (OF), which
      is a multidimensional coordinate frame, is associated with each data point
      indicating the point's preferred subspace configuration. Based on the similarity
      between the subspaces, novel mechanisms of subspace evolution and voting are
      developed. By filtering the outliers due to their structural incompatibility, the
      subspace configurations will emerge. Compared with most existing factorization
      based algorithms that cannot correctly segment correlated motions, such as
      motions of articulated objects, the proposed method has a robust performance in
      both independent and correlated motion segmentation. A number of controlled and
      real experiments show the effectiveness of the proposed method. However, the
      current approach does not deal with transparent motions and motion subspaces of
      different dimensions.

PMID- 16402623
TI  - Globally minimal surfaces by continuous maximal flows.
AB  - In this paper, we address the computation of globally minimal curves and surfaces
      for image segmentation and stereo reconstruction. We present a solution,
      simulating a continuous maximal flow by a novel system of partial differential
      equations. Existing methods are either grid-biased (graph-based methods) or
      suboptimal (active contours and surfaces). The solution simulates the flow of an
      ideal fluid with isotropic velocity constraints. Velocity constraints are defined
      by a metric derived from image data. An auxiliary potential function is
      introduced to create a system of partial differential equations. It is proven
      that the algorithm produces a globally maximal continuous flow at convergence,
      and that the globally minimal surface may be obtained trivially from the
      auxiliary potential. The bias of minimal surface methods toward small objects is
      also addressed. An efficient implementation is given for the flow simulation. The
      globally minimal surface algorithm is applied to segmentation in 2D and 3D as
      well as to stereo matching. Results in 2D agree with an existing minimal contour
      algorithm for planar images. Results in 3D segmentation and stereo matching
      demonstrate that the new algorithm is robust and free from grid bias.

PMID- 16402625
TI  - Feature-based detection of facial landmarks from neutral and expressive facial
      images.
AB  - Feature-based method for detecting landmarks from facial images was designed. The
      method was based on extracting oriented edges and constructing edge maps at two
      resolution levels. Edge regions with characteristic edge pattern formed landmark
      candidates. The method ensured invariance to expressions while detecting eyes.
      Nose and mouth detection was deteriorated by happiness and disgust.

PMID- 16402624
TI  - Optimal surface segmentation in volumetric images--a graph-theoretic approach.
AB  - Efficient segmentation of globally optimal surfaces representing object
      boundaries in volumetric data sets is important and challenging in many medical
      image analysis applications. We have developed an optimal surface detection
      method capable of simultaneously detecting multiple interacting surfaces, in
      which the optimality is controlled by the cost functions designed for individual
      surfaces and by several geometric constraints defining the surface smoothness and
      interrelations. The method solves the surface segmentation problem by
      transforming it into computing a minimum s-t cut in a derived arc-weighted
      directed graph. The proposed algorithm has a low-order polynomial time complexity
      and is computationally efficient. It has been extensively validated on more than
      300 computer-synthetic volumetric images, 72 CT-scanned data sets of different
      sized plexiglas tubes, and tens of medical images spanning various imaging
      modalities. In all cases, the approach yielded highly accurate results. Our
      approach can be readily extended to higher-dimensional image segmentation.

PMID- 16402626
TI  - Consistency checks for particle filters.
AB  - An "inconsistent" particle filter produces--in a statistical sense--larger
      estimation errors than predicted by the model on which the filter is based. Two
      test variables are introduced that allow the detection of inconsistent behavior.
      The statistical properties of the variables are analyzed. Experiments confirm
      their suitability for inconsistency detection.

PMID- 16402627
TI  - Reduced complexity rotation invariant texture classification using a blind
      deconvolution approach.
AB  - In this paper, we present a texture classification procedure that makes use of a
      blind deconvolution approach. Specifically, the texture is modeled as the output
      of a linear system driven by a binary excitation. We show that features computed
      from one-dimensional slices extracted from the two-dimensional autocorrelation
      function (ACF) of the binary excitation allows representing the texture for
      rotation-invariant classification purposes. The two-dimensional classification
      problem is thus reconduced to a more simple one-dimensional one, which leads to a
      significant reduction of the classification procedure computational complexity.

PMID- 16402628
TI  - Boosting color saliency in image feature detection.
AB  - The aim of salient feature detection is to find distinctive local events in
      images. Salient features are generally determined from the local differential
      structure of images. They focus on the shape-saliency of the local neighborhood.
      The majority of these detectors are luminance-based, which has the disadvantage
      that the distinctiveness of the local color information is completely ignored in
      determining salient image features. To fully exploit the possibilities of salient
      point detection in color images, color distinctiveness should be taken into
      account in addition to shape distinctiveness. In this paper, color
      distinctiveness is explicitly incorporated into the design of saliency detection.
      The algorithm, called color saliency boosting, is based on an analysis of the
      statistics of color image derivatives. Color saliency boosting is designed as a
      generic method easily adaptable to existing feature detectors. Results show that
      substantial improvements in information content are acquired by targeting color
      salient features.

PMID- 16402629
TI  - Learning vector quantization with training data selection.
AB  - In this paper, we propose a method that selects a subset of the training data
      points to update LVQ prototypes. The main goal is to conduct the prototypes to
      converge at a more convenient location, diminishing misclassification errors. The
      method selects an update set composed by a subset of points considered to be at
      the risk of being captured by another class prototype. We associate the proposed
      methodology to a weighted norm, instead of the Euclidean, in order to establish
      different levels of relevance for the input attributes. The technique was
      implemented on a controlled experiment and on Web available data sets.

PMID- 16402630
TI  - Recovering articulated pose: a comparison of two pre and postimposed constraint
      methods.
AB  - We contrast the performance of two methods of imposing constraints during the
      tracking of articulated objects, the first method preimposing the kinematic
      constraints during tracking and, thus, using the minimum degrees of freedom, and
      the second imposing constraints after tracking and, hence, using the maximum.
      Despite their very different formulations, the methods recover the same pose
      change. Further comparisons are drawn in terms of computational speed and
      algorithmic simplicity and robustness, and it is the last area which is the most
      telling. The results suggest that using built-in constraints is well-suited to
      tracking individual articulated objects, whereas applying constraints afterward
      is most suited to problems involving contact and breakage between articulated (or
      rigid) objects, where the ability to test tracking performance quickly with
      constraints turned on or off is desirable.

PMID- 16402631
TI  - Etanercept for psoriasis: two case reports.
AB  - Psoriasis is a chronic inflammatory skin disorder. Recent advances in the
      understanding of its immunological basis have led to its redefinition as being T
      cell mediated. New biological agents have been developed as effective selective
      target therapies and promise to be an alternative to conventional systemic
      medications. Etanercept is a recombinant human protein recently approved for
      psoriatic arthritis treatment that has activity against tumor necrosis factor
      alpha (TNF-alpha). It is composed of the human TNF receptor linked to the Fc
      portion of human IgG1. TNF-alpha seems to play a key role in the pathogenesis of
      psoriasis and psoriatic arthritis. Therefore, etanercept TNF antagonism is an
      effective approach for severe psoriasis. We describe two case reports of severe
      recalcitrant psoriasis, also with arthritis, that showed a remarkable improvement
      with etanercept, with no adverse events.

PMID- 16402632
TI  - Treatment of guttate psoriasis with a new two-compound product containing
      calcipotriol and betamethasone dipropionate.
AB  - We report a case of guttate psoriasis in a 28-year-old woman who had been
      suffering from scalp psoriasis from the age of 14. After an upper respiratory
      infection she presented with the typical exanthema of guttate psoriasis. Despite
      initial treatment with antibiotics and emollients, the rash continued to spread.
      Two months after the flare of psoriasis we decided to treat the patient with
      calcipotriol and betamethasone dipropionate ointment applied once daily, using an
      intermittent treatment modality. The lesions disappeared and despite two small
      recurrences on the legs we managed to maintain clearance after a 2-year follow
      up. Although the application of calcipotriol and betamethasone dipropionate
      ointment was cumbersome, due to the extent of the eruption, the result was highly
      effective and safe without any lesional/perilesional adverse reaction during
      application and with normal blood examinations.

PMID- 16402633
TI  - Evaluation of cytokine serum levels in patients with plaque-type psoriasis.
AB  - Psoriasis is a chronic debilitating cutaneous disorder that affects both sexes
      and appears clinically as inflamed, edematous skin lesions covered with a silvery
      white scale. Strong evidence suggests that immune mechanisms are implicated in
      its pathogenesis, such as persistent activation of T-lymphocytes, excessive
      proliferation of keratinocytes and reactivation of proto-oncogenes and other
      elements. Additionally, several recent studies have demonstrated that cytokines
      play a significant role in the pathogenesis of the disease, as they can be found
      in the affected skin of psoriatic patients. In this study we evaluated levels of
      circulating cytokines in the serum of 45 Greek psoriatic patients before
      initiation of treatment and compared the results with those in 45 healthy
      volunteers. According to our findings interleukin (IL)-2, IL-10, IL-12 and tumor
      necrosis factor-alpha (TNF-alpha) levels were statistically significantly
      elevated in the serum of psoriatic patients before therapy compared with those of
      controls. IL-6 serum levels did not differ between psoriatic patients and healthy
      volunteers. Conversely, interferon-gammaserum levels of psoriatic patients were
      statistically significantly lower than those of healthy volunteers.

PMID- 16402634
TI  - The effect of D-003 (10 mg/day) on biochemical parameters of bone remodelling in
      postmenopausal women: a randomized, double-blind study.
AB  - Biphosphonates, which are antiresorptive agents used to treat osteoporosis,
      inhibit the mevalonate pathway, preventing protein prenylation and inhibiting
      osteoclast activity. Statins decrease cholesterol biosynthesis by blocking the
      mevalonate pathway and have been reported to have beneficial effects on bone. D
      003 is a mixture of high molecular weight acids purified from sugarcane wax that
      inhibits cholesterol biosynthesis before mevalonate production. D-003 prevents
      bone loss and resorption in rats with osteoporosis induced with ovariectomy or
      corticoids. Biochemical markers of bone turnover are used to monitor the short
      term efficacy of antiosteoporotic therapy. This randomized, double-blind, placebo
      controlled study was undertaken to investigate the short-term effects of D-003
      (10 mg/day) on biochemical markers of bone turnover in postmenopausal women with
      low bone mineral density (BMD). After 4 weeks on a low-fat diet, 34 women were
      randomized to D-003 (10 mg/day) or placebo for 6 months. Pre- and post-treatment
      samples were analyzed for urinary excretion of deoxypyridinoline (DPD)/creatinine
      (Cr), a marker of bone resorption, and serum bone specific alkaline phosphatase
      (BSAP), a marker of bone formation. The effects on lipid profile and safety
      indicators, as well as adverse events (AE), were investigated. D-003 (10 mg/day)
      lowered urinary excretion of tDPD/Cr versus baseline (20.6%) (p < 0.001) and
      placebo (33.7%) (p < 0.01), but did not modify serum BSAP. D-003 decreased low
      density lipoprotein-cholesterol (LDL-C) (32.8%), total cholesterol (TC) (16.4%)
      and the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (34.7%), increased
      HDL-C (30.3%) (p < 0.001) and did not modify triglycerides. The effects on these
      variables were significant as early as 3 months after treatment initiation. D-003
      was well tolerated. Three patients (one in the placebo group and two in the D-003
      group) withdrew from the study. Two of these withdrawals were due to AE:
      abdominal pain (placebo) and heartburn (D-003). Five patients (four in the
      placebo group [22.2%] and one in the D-003 group [6.3%]) reported mild AE. In
      conclusion, D-003 (10 mg/day) reduced urinary excretion of tDPD/Cr, a bone
      resorption marker and did not change serum BSAP, a bone formation marker, while
      it lowered cholesterol in study patients. These preliminary results suggest that
      D-003 could be useful in treating postmenopausal women with low BMD. However, the
      potential value of D-003 in treating or preventing osteoporosis deserves further
      clinical investigation.

PMID- 16402635
TI  - Effects of ranitidine on quality of gastric ulcer healing compared with
      famotidine: a randomized, controlled, multicenter trial.
AB  - Ranitidine has been found to have anti-inflammatory action as well as
      antisecretory action in experimental models. However, there are no reports in
      human gastric ulcer. The aim of this study was to investigate the effects of
      ranitidine compared with those of famotidine on the quality of gastric ulcer
      healing. We randomly assigned 69 consecutive patients with gastric ulcers to
      ranitidine (n = 34) or famotidine (n = 35) for 12 weeks, with endoscopic
      assessment of the quality of gastric ulcer healing and histological assessment of
      gastric mucosa 12 weeks after treatment started. Ulcer healing rates of over 95%
      were very similar in the two groups. The rates of ulcer scars with a flat pattern
      (good-quality healing) were significantly higher in the ranitidine group than in
      the famotidine group (per protocol, 63.0% and 34.5%, p = 0.033). The neutrophil
      infiltration score in the body mucosa treated with famotidine, but not
      ranitidine, significantly increased after treatment. In contrast, the mononuclear
      cell infiltration score in the antral mucosa treated with ranitidine, but not in
      that treated with famotidine, had significantly decreased. In conclusion, initial
      therapy with ranitidine significantly improved the quality of gastric ulcer
      healing and the histological scores of gastric mucosa compared with famotidine.

PMID- 16402636
TI  - Breath alcohol concentrations in Japanese outpatients following paclitaxel and
      docetaxel infusion.
AB  - Patients receiving paclitaxel or docetaxel also receive a significant amount of
      ethanol, as both products contain ethanol as solvent. Patients in our clinics
      have occasionally exhibited signs of alcohol intoxication immediately after
      paclitaxel infusion. In 2002, the Japanese government lowered the minimum ethanol
      concentration for the definition of drunk driving, with the threshold breath
      alcohol concentration (BRAC) of 0.15 mg/l. The aim of this study was to measure
      BRAC in Japanese outpatients treated with paclitaxel or docetaxel and to assess
      intoxication according to this standard. Fifty-two Japanese patients were
      enrolled from October 2003 to February 2004. Patient characteristics were as
      follows: male/female, 13/39: median age, 71 (range: 34-78); breast/lung/ovarian
      cancer 24/16/12; and paclitaxel/docetaxel treatment: 36/16, respectively. The
      mean total doses of paclitaxel or docetaxel were 178 mg (range: 107-300) and 53
      mg (30-100), respectively. Breath samples were measured three times immediately
      following the infusion of paclitaxel or docetaxel via ethyl alcohol detector and
      the mean value was recorded. BRAC was detected in 20 patients (56%) with
      paclitaxel and in none of the docetaxel patients. BRAC was measured again 30 min
      after the initial measurement in BRAC-detected cases with the patients'
      permission. In four of six BRAC-remeasured patients, BRAC became undetectable
      after 30 min. There was no correlation between the total doses of paclitaxel and
      BRAC or between the infusion rates of paclitaxel and BRAC. In conclusion,
      clinicians should recognize the potential for alcohol intoxication with
      paclitaxel administration. Patients should be instructed to avoid driving on the
      day of paclitaxel administration.

PMID- 16402637
TI  - Evidence supporting endoscopic sinus surgery in the management of adult chronic
      rhinosinusitis: a systematic review.
AB  - BACKGROUND: Evidence-based medicine calls for a critical evaluation of the
      scientific evidence for treatments of disease. This report synthesizes the
      available evidence on the use of endoscopic sinus surgery (ESS) in the management
      of adult chronic rhinosinusitis (CRS) examining the clinical question: "In adults
      with CRS who have failed medical management, does ESS improve symptoms and/or
      quality of life (QOL)?" METHODS: The American Rhinologic Society and the American
      Academy of Otolaryngology-Head and Neck Surgery convened a steering committee
      composed of the authors. Primary research articles evaluated for this report were
      identified using appropriate search terms and a Medline search. Two authors
      independently reviewed each article. Articles were assigned an evidence level
      based on accepted guidelines (level 1 = randomized trials; level 2 = prospective
      cohort studies with comparison group; level 3 = case-control studies; level 4 =
      retrospective case series; level 5 = expert opinion). RESULTS: We identified 886
      abstracts to review, retrieved 75 articles for full review, and included 45
      articles in our report. The vast majority of articles represented level 4
      evidence (n = 42) and two articles represented level 5 evidence. One article was
      identified that qualified for level 2 evidence. All of these articles generally
      supported the finding that ESS improves symptoms and/or QOL in adult patients
      with CRS. CONCLUSION: There is substantial level 4 evidence with supporting level
      2 evidence that ESS is effective in improving symptoms and/or QOL in adult
      patients with CRS. Future research efforts should focus on prospective studies
      that include appropriate comparison groups in their design.

PMID- 16402638
TI  - Bacterial infection in chronic rhinosinusitis: a controlled paired analysis.
AB  - BACKGROUND: The aim of this study was to determine if pathogenic bacteria are
      involved in the pathogenesis of chronic rhinosinusitis (CRS). METHODS: A
      consecutive series of adult patients with unilateral sinus disease determined by
      unilateral radiographic involvement or unilateral purulent secretions was
      microbiologically studied. Aerobic and anaerobic bacterial and fungal cultures
      were obtained during endoscopic sinus surgery from purulent secretions or tissue
      culture. Positive culture rates were compared between the diseased sinus and the
      contralateral nondiseased (control) sinus to determine if pathogenic bacteria
      were more commonly recovered from the diseased sinuses. RESULTS: Forty-nine adult
      patients completed the study with appropriate microbiological data. Coagulase
      negative staphylococci were the most commonly recovered bacteria followed by
      Staphylococcus aureus from the diseased side of the sinuses with similar findings
      for the control sinus. Bacterial species were recovered from 87.8% of the
      diseased side of the sinuses versus 85.7% from the control sinuses (p = 0.50).
      Reanalysis with coagulase-negative staphylococci considered as nonpathogen showed
      a 46.9 and 49.0% positive bacterial culture rate in diseased and control groups,
      respectively (p = 0.50). No significant difference in positive anaerobic culture
      rates were identified between groups (59.1% diseased versus 55.1% control,
      respectively, p = 0.61). Antibiotic resistance rates were no different between
      bacteria cultured from diseased sinuses versus control (p = 0.115). CONCLUSION:
      Both aerobic and anaerobic bacterial species may be recovered from both diseased
      and nondiseased sinuses in patients with CRS. These findings cast some doubt on
      the exact etiologic role of bacteria in CRS, suggesting other factors or other
      agents also may be responsible in CRS pathogenesis.

PMID- 16402639
TI  - Expression of cell cycle regulatory proteins and analysis of apoptosis in normal
      nasal mucosa and in nasal polyps.
AB  - BACKGROUND: The etiopathogenesis of nasal polyps still is to be clarified.
      Although hyperplasia is a typical feature of these pathological processes, little
      attention has been paid to specific aspects of cellular growth in polyps. We have
      evaluated the expression and localization of some of the regulatory proteins that
      direct the cell through the specific sequence of events culminating in mitosis or
      apoptosis in nasal polyps. METHODS: Twenty samples of nasal polyps and 20 samples
      of normal nasal mucosa have been analyzed for apoptotic index by detecting the
      DNA 3'OH ends deriving from DNA fragmentation. Moreover, they have been evaluated
      by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53,
      p21, p27, murine double minute clone 2, and Bcl-2. RESULTS: We have identified a
      greater proportion of proliferating cells in the lining epithelial cells of the
      polyps when compared with the normal mucosa as stained with anti-Ki-67
      antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis
      were observed in nasal polyps compared with the normal mucosa, whereas no
      variation of p27 expression was observed. The p21 and cyclins A and B1 were
      rarely expressed in both pathological and normal tissue. CONCLUSION: The p53
      based control system of cell cycle progression appears to be altered in nasal
      polyps, potentially leading to an abrogation of the DNA damage checkpoint.
      Evaluation of the expression of the regulatory proteins that direct the cells
      throughout their cycle in nasal polyps may allow a better understanding of the
      biological behavior and clinical outcome of these benign pathological entities.

PMID- 16402640
TI  - Role of macrophage migration inhibitory factor in paranasal sinus mucocele.
AB  - BACKGROUND: Little is known about the immunologic aspects and the pathogenesis of
      the paranasal sinus mucocele. METHODS: The fluids of paranasal sinus mucoceles
      were obtained from 12 subjects. The concentration of macrophage migration
      inhibitory factor (MIF), interleukin 1beta, tumor necrosis factor alpha, and
      regulated on activation normal T cell expressed and secreted (RANTES) were
      determined by enzyme-linked immunosorbent assay, and the levels of endotoxin were
      detected with kinetic Turbidimetric Assay. RESULTS: MIF and endotoxin were
      detected in the fluid of all samples, whereas interleukin-1beta and RANTES were
      detected in 1 and 3 subjects out of 12 samples. Tumor necrosis factor alpha was
      not detected in any of the samples. A significant positive correlation between
      the levels of MIF and the period with symptoms such as pain, swelling of face,
      and visual disturbance was observed. CONCLUSION: These findings suggest that MIF
      and endotoxin may play an important role in the pathogenesis of paranasal sinus
      mucocele. MIF may be an important factor causing the development and exacerbation
      of the disease.

PMID- 16402641
TI  - Does nitrogen dioxide affect inflammatory markers after nasal allergen challenge?
AB  - BACKGROUND: Exposure to high ambient levels of nitrogen dioxide (NO2) enhances
      the bronchial inflammatory reaction to allergen in humans. We tested whether this
      NO2 effect occurs also in the upper airways. METHODS: Sixteen allergic subjects
      with rhinitis and mild asthma were exposed at rest to either purified air or 500
      microg/m3 NO2 for 30 minutes, followed 4 hours later by a nasal allergen
      challenge. Nasal lavage was performed before air/NO2 exposure, before allergen
      challenge, and 1, 4 and 18 hours after allergen challenge. Symptoms were
      recorded. RESULTS: The percentage of eosinophils and neutrophils, eosinophil
      cationic protein, and myeloperoxidase were similar after exposure to air +
      allergen and to NO2 + allergen. We noticed a tendency to increased sneezing the
      day after exposure to NO2 + allergen. CONCLUSION: The priming effect of an
      ambient brief NO2 exposure on subsequent allergic response was not noticeable in
      activation of inflammatory cells and mediators in the upper airways.

PMID- 16402642
TI  - What is the correlation between ratings and measures of olfactory function in
      patients with olfactory loss?
AB  - BACKGROUND: Major complaints of many patients with olfactory dysfunction relate
      to the impairment of quality of life. Nevertheless, it is unclear to what extent
      there is a correlation between ratings of olfactory abilities/impairment and
      olfactory function. METHODS: Patients with olfactory dysfunction (n = 152) were
      examined psychometrically using the "Sniffin' Sticks" test battery. Ratings of
      olfactory function and ratings of impairment were recorded using visual analog
      scales. RESULTS: Following standardized olfactory testing, 78 of the 152 patients
      were categorized as functionally anosmic, 64 as hyposmic, and 10 as normosmic.
      Groups differed significantly with regard to ratings of olfactory function.
      Functionally anosmic patients rated impairment to be significantly higher
      compared with hyposmic and normosmic patients. Ratings of olfactory function
      correlated significantly with measured olfactory function (r = +0.57) and ratings
      of impairment (r = -0.30). CONCLUSION: There was a moderate correlation between
      ratings and measures of olfactory function. On average, functionally anosmic
      patients recognized their olfactory loss, although, on an individual basis, there
      were striking differences between measures and ratings of olfactory function.

PMID- 16402643
TI  - The effect of a hyaluronic acid-based nasal pack on mucosal healing in a sheep
      model of sinusitis.
AB  - BACKGROUND: A hyaluronic acid-based nasal pack has been shown previously to have
      a beneficial effect on mucosal healing in a healthy sheep model. However,
      endoscopic sinus surgery (ESS) usually is performed in the presence of infection
      and inflammation. The aim of this study was to examine the efficacy of hyaluronic
      acid-based nasal packing on mucosal healing in a sheep model of chronic
      sinusitis. METHODS: A standardized sheep model of chronic sinusitis was used.
      Full-thickness mucosal injuries were performed under endoscopic guidance with a
      microdebrider. Adjacent wounds were created between the lateral nasal wall and
      the ethmoid turbinate. Then, the injuries were either packed with a dissolvable
      hyaluronic acid-based pack or left unpacked to serve as a control. Serial
      biopsies of the healing mucosa were performed at days 28, 56, 84, and 112
      postsurgery, and the presence or absence of adhesions between the ethmoid
      turbinate and lateral nasal wall was noted. The biopsy specimens were assessed
      for reepithelialization and epithelial height using light microscopy, and for
      reciliation using scanning electron microscopy. RESULTS: There was no significant
      difference in reepithelialization or relative epithelial height between the
      packed sides and the control sides at any time point. There was a statistically
      significant difference in reciliation between the two groups at day 112 but this
      was not deemed clinically significant. The packing had no significant effect on
      adhesion formation. CONCLUSION: In the sheep model of chronic sinusitis, a
      dissolvable hyaluronic acid-based pack did not have any significant effect on
      mucosal healing or adhesions formation after ESS, as assessed by examining
      reepithelialization, epithelial height, reciliation, and the presence of
      adhesions.

PMID- 16402644
TI  - The effect of an expandable polyvinyl acetate (Merocel) pack on the healing of
      the nasal mucosa of sheep.
AB  - BACKGROUND: There is a lack of knowledge about the healing of the nasal
      respiratory mucosa after endoscopic sinus surgery (ESS). Nasal packs often are
      placed after ESS in an attempt to improve hemostasis and reduce adhesion
      formation. Most nasal packs need to be removed in the postoperative period. This
      is uncomfortable for the patient and the affect of these packs on the healing
      process is unknown. METHODS: We have standardized the sheep as a suitable animal
      model to examine the healing of the nasal epithelium after ESS. The nasal mucosa
      of sheep was wounded under endoscopic guidance and either packed with expandable
      polyvinyl acetate-based pack (Merocel), which was removed at the 5th
      postoperative day, or left unpacked to serve as control. Serial biopsies of the
      wounded area were taken every 28 days, up to 112 days postwounding, for
      examination using light and scanning electron microscopy. RESULTS: There was no
      significant difference in the rate of reepithelialization between the packed and
      control sides of the sheep (p > 0.05). There was no significant difference in the
      total amount of surface cilia coverage between the packed and control sides at
      any time points (p > 0.05). There was no significant difference in the maturity
      of the cilia between the packed and control sides at any time points (p > 0.05).
      CONCLUSION: The use of Merocel packing postoperatively neither impairs nor
      promotes wound healing in the postoperative period.

PMID- 16402645
TI  - Long-term outcomes of endoscopic repair of cerebrospinal fluid leaks and
      meningoencephaloceles.
AB  - BACKGROUND: The management and surgical approach to cerebrospinal fluid (CSF)
      leaks and meningoencephaloceles have undergone transformation throughout the last
      10 years. It is our interest to examine the long-term surgical outcome and
      reoccurrence rates of CSF leaks or meningoencephaloceles in patients having
      endoscopic surgical repair. METHODS: We performed a retrospective evaluation of
      50 patients that underwent endoscopic surgical repair of a CSF leak,
      meningoencephalocele, or both, between September 1985 and October 2003. RESULTS:
      Cumulatively, reoccurrence rates were 15% (7/47) among the CSF leak patients with
      an average time frame for reoccurrence ranging from 1 to 25 months (average, 7
      months). Patients with meningoencephaloceles had an overall reoccurrence rate of
      8% (1/13). In addition, a Medline search on CSF leaks and meningoencephaloceles
      provided the names of 32 authors that have studied outcomes of endoscopic
      surgical repair. Of the 151 patients still followed in the 5- to 10-year
      postoperative group, there were 37 recurrences of CSF leaks and 5 reoccurrences
      of the meningoencephaloceles with a total recurrence rate of 27% (37 + 5/151). Of
      the 19 patients still followed in the >10-year postoperative group, there were
      three reoccurrences of CSF leaks and no reoccurrences of meningoencephaloceles,
      giving a reoccurrence rate of 16% (3 + 0/19). CONCLUSION: Based on our cumulative
      results, a reoccurrence of a CSF leak or meningoencephalocele after endoscopic
      repair will occur within the first 2 years postoperatively. Once patients pass
      these postoperative time frames they are relatively free of reoccurrence from
      this very effective surgical management. Endoscopic repair results are better
      than craniotomy with much less morbidity.

PMID- 16402646
TI  - The management of rhinitis in patients with functional epiphora: a randomized
      controlled crossover trial.
AB  - BACKGROUND: Nasolacrimal duct obstruction, secondary to inflammation of the nasal
      mucosa, can result in epiphora. This can be treated successfully with topical
      corticosteroids, avoiding the need for surgery. This study tests the hypothesis
      that treating clinically significant rhinitis improves the symptoms of epiphora.
      METHODS: A randomized controlled crossover trial (pilot study) was performed at
      the Cumberland Infirmary, Carlisle. Patients were assessed in an epiphora clinic
      by a consultant ophthalmologist and were included in the trial if they had
      bilateral functional epiphora, i.e., the nasolacrimal duct was patent on
      syringing. Twenty-three patients were then referred to a consultant
      otolaryngologist, where the severity of rhinitis and epiphora were assessed using
      visual analogue scales, subjective scoring, and clinical assessment. The 11
      patients suitable for the study were randomized into two groups. The treatment
      group received nasal corticosteroids and the control group received no treatment,
      both groups changing treatment arms at a specified point. Subjective and
      objective scores were assessed at the beginning, midpoint, and end of each
      treatment period. RESULTS: Seven of 11 patients showed an improvement in epiphora
      scores with topical therapy. Six patients documented a symptomatic improvement.
      Eight patients showed an improvement in symptoms and signs of rhinitis, with two
      patients continuing on nasal corticosteroids for nasal symptoms only. There was a
      statistically significant improvement in both epiphora symptom scores and
      clinical findings of rhinitis in patients treated with nasal steroids (p = 0.021
      and 0.019, respectively). CONCLUSION: Epiphora secondary to rhinitis can be
      treated successfully with intranasal steroids. Patients with epiphora should be
      asked about symptoms of rhinitis and should always have their nose examined for
      evidence of intranasal pathology.

PMID- 16402647
TI  - Montelukast effectively treats the nighttime impact of seasonal allergic
      rhinitis.
AB  - BACKGROUND: Nighttime problems constitute a significant burden on the quality of
      life of patients with seasonal allergic rhinitis (SAR). The aim of this study was
      to evaluate the effectiveness of montelukast on nighttime AR symptoms. METHODS:
      In seven multicenter, double-blind, parallel-group trials, nighttime problems
      were assessed as the nighttime symptoms score (NSS), an average of three
      individual symptom scores: difficulty going to sleep, nighttime awakening, and
      nasal congestion on awakening (each rated 0 = none to 3 = severe). Patients (aged
      15-82 years) were randomized to receive montelukast, 10 mg (n = 1751), placebo (n
      = 1557), or the positive control loratadine, 10 mg (n = 1616). RESULTS: In a
      combined analysis, changes from baseline (mean +/- SE) in NSS were -0.28 +/-
      0.01, -0.16 +/- 0.01, and -0.24 +/- 0.01 for the montelukast, placebo, and
      loratadine groups, respectively. Difference versus placebo in least-squares mean
      change from baseline were -0.11 (95% confidence interval, -0.14, -0.08; p < or =
      0.001) for montelukast and -0.09 (-0.12, -0.06; p < or = 0.001) for loratadine.
      Strong baseline correlations (R > 0.70; p < 0.001) of NSS and two of its
      individual symptoms with the sleep domain of the validated Rhinoconjunctivitis
      Quality of Life Questionnaire support the validity and importance of measuring
      nighttime morbidity in SAR. Furthermore, a clinically important benefit of
      montelukast on the nighttime impact of SAR was shown using an analysis anchored
      on the Patient's Global Evaluation. CONCLUSION: These data underscore the
      importance of nighttime problems in patients with SAR and the need to treat
      nighttime symptoms. In these studies, montelukast significantly improved the NSS,
      a clinically relevant and valid measure in patients with SAR.

PMID- 16402648
TI  - Nasal septal suture technique versus nasal packing after septoplasty.
AB  - BACKGROUND: The aim of this study was to compare eustachian function and blood
      gas changes with nasal packing (NP) and nasal septal suturing (NSS) after
      septoplasty. METHODS: Eighty patients who have nasal septal deviation and who
      otherwise are healthy were studied. Forty of these patients had finger glove NPs
      in their nasal cavities for 48 hours after septoplasty. Another 40 patients had
      NSS performed after septoplasty. Acoustic tympanometry and pH, P(CO2), and P(O2)
      analyses of arterial blood were performed preoperatively and 48 hours
      postoperatively. RESULTS: We observed a statistically significant increase in
      middle ear pressure (p < 0.001) and a significant reduction of P(O2) (p < 0.001)
      and increase of P(CO2) (p = 0.041) in the NP group but no difference in the NSS
      group, postoperatively. CONCLUSION: NSS should be preferred as an alternative to
      intranasal packing.

PMID- 16402649
TI  - Endoscopic orbital decompression for Graves' ophthalmopathy.
AB  - BACKGROUND: Graves' ophthalmopathy generates a volume excess for the orbital
      cavity, which may produce proptosis, pain, exposure keratitis, diplopia, and
      optic neuropathy. Endoscopic orbital decompression expands the orbital cavity
      into the ethmoid cavity and medial maxillary sinus. This retrospective study
      documents the outcomes after endoscopic orbital decompression for patients with
      Graves' ophthalmopathy. METHODS: Data collected included demographic information,
      symptom resolution, complications related to the surgery, reduction in proptosis,
      subsequent need for eye muscle surgery, and hospital length of stay. Between July
      1989 and April 2003, 62 patients were referred for endoscopic orbital
      decompression (often unilateral). RESULTS: Three patients refused use of their
      medical records for research purposes. Seventy percent were women; the average
      age of the study group was 49 years. Preoperatively, 63% of the patients had
      diplopia and optic neuropathy was noted in 27%. Two patients had a cerebrospinal
      fluid leak identified and managed during the decompression. No postoperative
      leaks occurred. Twenty-five percent of patients did not require eye muscle
      surgery. Forty-eight percent of the patients underwent one procedure to manage
      diplopia. The average reduction in proptosis was 2.5 mm. Fifty-four percent were
      managed as an outpatient and 27% underwent a 23-hour observation period.
      CONCLUSION: This data supports the safety, efficiency, and efficacy of endoscopic
      orbital decompression for unilateral and bilateral Graves' ophthalmopathy. Eye
      muscle surgery frequently will be required to manage diplopia after
      decompression.

PMID- 16402650
TI  - Nasal congestion and hyperventilation syndrome.
AB  - BACKGROUND: This article evaluates the prevalence of hyperventilation syndrome
      (HVS) in patients who continue to complain of ongoing nasal congestion, despite
      an apparently adequate surgical result and appropriate medical management.
      METHODS: Prospective case series of 14 patients from June 2002 to October 2003
      was performed. Patients, who presented complaining of nasal congestion after
      previous nasal surgery and who appeared to have an adequate nasal airway with no
      evidence of nasal valve collapse, were evaluated for HVS. When appropriate, nasal
      steroids and oral antihistamines also had been tested without success. Three
      patients had end-tidal P(CO2) levels measured and five patients underwent
      breathing reeducation. RESULTS: All patients had an elevated respiratory rate
      (>18 breaths/minute) with an upper thoracic breathing pattern. Twelve of the 14
      patients complaining of nasal obstruction had an elevated Nijmegen score
      indicative of HVS. An average number of 2.5 procedures had been performed on each
      patient. End-tidal P(CO2) levels were < or = 35 mmHg in the three patients who
      had expired P(CO2) levels measured. Breathing retraining was successful in
      correcting the nasal congestion in two of five patients. CONCLUSION: HVS should
      be included in the differential diagnosis of patients presenting with nasal
      congestion, particularly after failed nasal surgery. One possible explanation is
      increased nasal resistance secondary to low arterial P(CO2) levels. Another
      possible explanation is reduced alae nasae muscle activity secondary to the
      reduced activity of serotonin-containing raphe neurons. Additional surgery may
      not necessarily be the answer in HVS patients complaining of nasal congestion.

PMID- 16402651
TI  - Is septoplasty alone adequate for the treatment of chronic rhinosinusitis with
      septal deviation?
AB  - BACKGROUND: The purpose of this study was to reveal the role of septoplasty in
      curing chronic rhinosinusitis (CRS) in patients with significant septal
      deviation. METHODS: This prospective study involved 26 patients with CRS and
      septal deviation. The patients were randomly divided into two groups according to
      the applied surgical procedures. In the first and second groups, septoplasty and
      septoplasty plus endoscopic sinus surgery were applied, respectively. Subjective
      (questionnaire) and objective (endoscopy and computerized tomography) success
      rates were used to analyze the results. RESULTS: Septoplasty alone and
      septoplasty plus endoscopic sinus surgery were applied in 57.7% (15/26) and 42.3%
      (11/ 26) of the patients, respectively. Success rates were 93.3% (14/15) and
      81.8% (9/11), subjectively (p > 0.05), and 66.7% (10/15) and 54.5% (6/11),
      objectively (p > 0.05), respectively in each group. CONCLUSION: We suggest that
      septoplasty alone can be adequate for the treatment of CRS with septal deviation.

PMID- 16402652
TI  - Tensile biomechanical properties of human nasal septal cartilage.
AB  - BACKGROUND: The biomechanical properties of human septal cartilage have yet to be
      fully defined and thereby limits our ability to compare tissue-engineered
      constructs to native tissue. In this study, we analyzed the tensile properties of
      human nasal septal cartilage with respect to axis of tension, age group, and
      gender. METHODS: Fifty-five tensile tests were run on human septal specimens
      obtained from 28 patients. Samples obtained in the vertical and anterior
      posterior (both above and within the maxillary crest) axes were subjected to
      equilibrium and dynamic tensile testing. RESULTS: The average values for
      strength, failure strain, equilibrium modulus and dynamic modulus were not found
      to be significantly different with respect to axis of tension testing, age group,
      or gender. Tensile results for septal cartilage were as follows: equilibrium
      modulus 3.01 +/- 0.39 MPa, dynamic modulus 4.99 +/- 0.49 MPa, strength 1.90 +/-
      0.24 MPa, and failure strain 0.35 +/- 0.03 mm/mm. CONCLUSION: We confirm that
      septal cartilage has weaker tensile properties compared to articular cartilage
      and found no difference in strength with respect to age, gender, or axis of
      tension (isotropic).

PMID- 16402653
TI  - Comparison of laser versus surface-touch registration for image-guided sinus
      surgery.
AB  - BACKGROUND: Use of image-guidance systems has become more popular in endoscopic
      sinus surgery. The laser registration technique has been used previously;
      however, a less expensive surface-touch registration technique recently has been
      developed. We compared the accuracy and speed of laser and surface-touch
      registration techniques. METHODS: Localization accuracy after laser and surface
      touch registration was examined after 15 endoscopic sinonasal procedures between
      July and September 2004. Compared anatomic locations included the nasofrontal
      angle, nasolabial angle, posterior maxillary wall, skull base, and posterior
      vomer. For each localization point, the degree of error (in millimeters) was
      measured in superior-inferior (SI), anterior-posterior (AP), and right-left (RL)
      dimensions. The length of time for each registration procedure was recorded for
      both techniques. RESULTS: Laser registration was significantly faster (mean, 20
      seconds) than surface-touch registration (mean, 20 seconds versus 63 seconds,
      respectively; p < 0.05). Laser registration was accurate within 0.3 mm in the SI
      direction, 0.4 mm in the AP direction, and 0.4 mm in the RL direction. Surface
      touch registration was accurate within 0.3 mm in the SI direction, 0.4 mm in the
      AP direction, and 0.3 mm in the RL direction. There was no significant difference
      between techniques for any anatomic point. In 97.7% of all points, accuracy was
      within 2 mm or less for both the laser and surface-touch registration.
      CONCLUSION: Surface-touch registration is significantly slower than laser
      registration but has virtually no difference in accuracy. Both techniques compare
      very favorably to the accuracy of other systems reported in the literature.

PMID- 16402655
TI  - Reassessing the relationship between disability insurance and workers'
      compensation.

PMID- 16402654
TI  - Isolated inflammatory sphenoid sinus disease: a revisitation of computed
      tomography indications based on presenting findings.
AB  - BACKGROUND: Isolated inflammatory sphenoid sinus disease (IISSD) can be difficult
      to diagnose. Frequently, history and physical are inadequate in establishing a
      diagnosis. Computed tomography (CT) is an excellent screening tool; however, it
      often is obtained late in the disease process because of vague symptoms at
      presentation. Identifying the most common presenting symptoms of IISSD may allow
      earlier detection and avoidance of more severe sequelae by determining earlier
      indications for CT. Presently, headache is not an indication for sinus CT.
      METHODS: A retrospective chart review of IISSD presentation was performed at our
      institution. A literature review was performed also to quantitatively document
      trends in presentation of IISSD, including characterization of headache symptoms
      by location. Cumulative findings were then compared with current CT indications
      to determine if presentation patterns warrant a change in indications for CT.
      RESULTS: A total of 361 cases were evaluated by our inclusion criteria. Headache
      was the most common finding (81.7%), particularly peri/retro-orbital, vertex, and
      frontal headache. Ocular changes (17.5%) and cranial nerve involvement (16.1%)
      were common also, but headache frequently was a solitary finding (42.6%). Twenty
      six IISSD cases were reviewed at our institution over 7 years, with similar
      results. Under current guidelines, the only IISSD findings that are indications
      for CT scan are the ophthalmologic and neurological complications. CONCLUSION:
      Not every headache necessitates a CT scan. However, the deep-seated vertex,
      frontal, and, particularly, peri/retro-orbital headaches, especially when
      aggravated by head movement and refractory to analgesics, as is often seen in
      IISSD, should be an indication for CT evaluation.

PMID- 16402656
TI  - Workers' compensation, Social Security Disability Insurance, and the offset: a
      fact sheet.
AB  - This article offers a brief summary of the workers' compensation and Social
      Security Disability Insurance programs. Information highlighted includes the
      differences between the two programs' types and terms of coverage. It compares
      the differing patterns in workers' compensation and Social Security disability
      benefits as a percentage of wages over the past few decades and considers the
      potential causes for such trends. The article also explains the offset provision
      included in the 1965 Social Security Amendments, the intention behind the offset,
      and how and when offsets are applied.

PMID- 16402657
TI  - Workers' compensation: a background for Social Security professionals.
AB  - This article provides a brief history and background of workers' compensation
      programs for occupationally injured and ill workers in the United States. It
      presents the basic principle involved in workers' compensation and briefly
      discusses the disability benefits to which workers are generally entitled. It
      also discusses why there are settlements in this disability program and the
      availability of information about the amounts paid in workers' compensation cases
      for obtaining an offset for Social Security Disability Insurance benefits paid to
      the worker. Finally, the article explains the rationale behind the public policy
      on coordination of Disability Insurance and workers' compensation in the new
      paradigm of disability and return to work.

PMID- 16402658
TI  - Compensating workers for permanent partial disabilities.
AB  - There is substantial variability in how state workers' compensation laws provide
      benefits to workers who have a permanent partial disability. The basic approaches
      used by the states can be classified into four groupings, although important
      differences exist within each group. Depending on the approach used, workers with
      similar injuries can receive substantially different amounts of benefits. Because
      compensating permanent partial disabilities frequently involves contention, the
      matters in dispute will depend on the approach used to determine benefits. The
      continuation of such differences in approach suggests that the states have not
      found a single "best practice" for determining what such benefits should be.

PMID- 16402659
TI  - Benefit adequacy in state workers' compensation programs.
AB  - This article summarizes several different methods used to measure the adequacy of
      wage replacement in state workers' compensation systems in the United States.
      Empirical research casts serious doubt on benefit adequacy, especially in the
      case of more serious disabilities.

PMID- 16402660
TI  - The fraction of disability caused at work.
AB  - Disability has high societal and personal costs. Various disparate federal and
      state programs attempt to address the economic and social needs of people with
      disabilities. Presumably workplace injuries and accidents are an important source
      of disability. Yet separate public policies and research literatures have evolved
      for these two social problems--disability and workplace injuries--despite their
      relatedness. This article seeks to document the overlap between these two
      phenomena in estimating the proportion of the disabled population whose
      disability was caused by workplace injury, accident, or illness using the Health
      and Retirement Study of 1992. The results point toward the need for initiatives
      to reduce disability that focus on work-related causes, which are a common
      pathway to disability, and that may result in substantial savings in federal
      programs.

PMID- 16402661
TI  - Design and implementation issues in Swedish individual pension accounts.
AB  - Sweden's new multipillar pension system includes a system of mandatory fully
      funded individual accounts. The Swedish system offers contributors more than 600
      fund options from a variety of private-sector fund managers. However, in the most
      recent rounds of fund choice, more than 90 percent of new labor market entrants
      have not made an active choice of funds and thus have ended up in a government
      sponsored default fund. The Swedish system offers a number of lessons about
      implementing a mandatory individual account tier. Centralized administration
      keeps administrative costs down but requires considerable lead time. A very large
      number of fund options are likely to be offered unless strong entry barriers are
      in place. Engaging new labor market entrants in fund choice is likely to be
      difficult. A significant percentage of those making an active fund choice may
      choose funds that are very specialized and risky. Finally, special care must be
      devoted to designing a default fund and continual consumer communication.

PMID- 16402662
TI  - Conceptualizing risk assessment methodology for genetically modified organisms.

PMID- 16402663
TI  - The co-existence between transgenic and non-transgenic maize in the European
      Union: a focus on pollen flow and cross-fertilization.
AB  - The ongoing discussion on the co-existence between genetically modified (GM) and
      non-GM crops becomes more important in the European Union (EU). With the recent
      inscription of 17 GM maize varieties in the common EU catalogue of varieties of
      agricultural plant species, the acreage of transgenic maize for market purposes
      is expected to increase in some European countries. In the EU, specific tolerance
      thresholds have been established for the adventitious and technically unavoidable
      presence of GM material in non-GM produce, and member states are elaborating
      legal frames to cope with co-existence. As maize is a cross-pollinated crop
      relying on wind for the dispersal of its pollen, technical management measures
      will be imposed to reduce cross-fertilization between transgenic and non
      transgenic maize. Various biological, physical and analytical parameters have
      been identified to play a role in the study of cross-fertilization in maize. This
      variability may hamper the comparison between research results and may complicate
      the definition of appropriate isolation distances and/or pollen barriers in order
      to limit out-crossing. The present review addresses these parameters and proposes
      containment measures in order to not exceed the legal labeling thresholds in
      maize.

PMID- 16402664
TI  - Biosafety considerations for selectable and scorable markers used in cassava
      (Manihot esculenta Crantz) biotechnology.
AB  - Cassava is an important subsistence crop grown only in the tropics, and
      represents a major source of calories for many people in developing countries.
      Improvements in the areas of resistance to insects and viral diseases, enhanced
      nutritional qualities, reduced cyanogenic content and modified starch
      characteristics are urgently needed. Traditional breeding is hampered by the
      nature of the crop, which has a high degree of heterozygosity, irregular
      flowering, and poor seed set. Biotechnology has the potential to enhance crop
      improvement efforts, and genetic engineering techniques for cassava have thus
      been developed over the past decade. Selectable and scorable markers are critical
      to efficient transformation technology, and must be evaluated for biosafety, as
      well as efficiency and cost-effectiveness. In order to facilitate research
      planning and regulatory submission, the literature on biosafety aspects of the
      selectable and scorable markers currently used in cassava biotechnology is
      surveyed. The source, mode of action and current use of each marker gene is
      described. The potential for toxicity, allergenicity, pleiotropic effects,
      horizontal gene transfer, and the impact of these on food or feed safety and
      environmental safety is evaluated. Based on extensive information, the selectable
      marker genes nptII, hpt, bar/pat, and manA, and the scorable marker gene uidA,
      all have little risk in terms of biosafety. These appear to represent the safest
      options for use in cassava biotechnology available at this time.

PMID- 16402665
TI  - Double recoverable block of function--a molecular control of transgene flow with
      enhanced reliability.
AB  - Despite all the achieved benefits and potential promises from recombinant DNA
      technology of plants, the potential of transgene spread to wild relatives and to
      non-transgenic crops is still of a wide-spread concern. We continue to develop
      recoverable block of function (RBF) technology for gene flow control in
      transgenic plants. RBF consists of two elements: blocking construct (BC) and
      recovering construct (RC). Natural expression of the BC (barnase) in embryos and
      sprouts blocks a physiological function essential for survival or reproduction of
      the transgenic plant (mRNA synthesis and germination). Artificially induced (heat
      shock treatment) RC (barstar) recovers the blocked function enabling transgenic
      plant to reproduce. In natural conditions without artificial induction of RC the
      transgenic plant can not reproduce itself. However, a single RBF may still fail
      because of the potential for mutations and gene silencing of the inserted
      constructs. To minimize the frequency of such an inactivation, we developed a
      double RBF, in which a single insert comprising two BC, flanking a transgene of
      interest, was constructed and transferred into tobacco (Nicotiana tabacum (L.)).
      We used a barstar gene driven by a heat shock or 35S promoter as a RC, and two
      different promoters were used for barnase genes in the BC. One BC contained a
      seed germination specific cysteine endopeptidase promoter (BC1) and the other
      contained the cruciferin promoter (BC2), which is active during fruit development
      and embryogenesis. Three alternative constructs of double RBF are described, and
      a segregating two-insert as well as a one-insert cassettes, were compared. One
      insert system comprising two BC with different nucleotide sequences but
      degenerate codons that expressed the same Barnase protein appeared to be the most
      reliable choice. The biological and molecular data obtained suggest that double
      RBF is a potent transgene containment technique that can safely be applied in
      agriculture.

PMID- 16402666
TI  - Field evidence for the exposure of ground beetles to Cry1Ab from transgenic corn.
AB  - Non-target organisms associated with the soil might be adversely affected by
      exposure to the CrylAb protein from Bacillus thuringiensis (Bt) in transgenic
      corn (Zea mays L.). To check for such exposure, we used ELISA to test for Cry1Ab
      in ground beetles collected live from fields with Bt corn residues and Bt corn
      (Bt/Bt), Bt corn residues and non-Bt crops (Bt/non-Bt), or non-Bt corn residues
      and non-Bt crops (non-Bt/non-Bt). In fields with Bt corn residues (Bt/Bt and
      Bt/non-Bt), Cry1Ab was present in all seven species of ground beetles examined
      (Agonum placidum, Bembidion rupicola, Clivina impressefrons, Cyclotrachelus
      iowensis, Harpalus pensylvanicus, Poecilus chalcites, and Poecilus lucublandus).
      For the two most abundant species, P. chalcites and P. lucublandus, the
      proportion of beetles with Cry1Ab was significantly higher in Bt/Bt fields (0.50
      1.0) and Bt/non-Bt fields (0.41-0.50) than in non-Bt/non-Bt fields (0.0). This is
      the first field evidence that some ground beetle species are exposed to Cry1Ab.
      The implications of exposure on the performance of these non-target organisms are
      unclear.

PMID- 16402667
TI  - Risks and prevention of sexually transmissible infections among women who have
      sex with women.
AB  - Health care providers working with women who have sex with women (WSW) have been
      ill-informed about a range of sexual health issues for these women. Pertinent
      issues include sexual behaviours that carry risks of sexually transmissible
      infection (STI), prevention strategies for safer sex and understanding
      experiences of abuse. A relative silence continues in all of these areas within
      the mainstream medical literature, textbooks, research and policy documents,
      which perpetuates medical ignorance. There is evidence that the prevalence of
      STIs among WSW is at least as high as among heterosexual women, if not higher
      among some sub-groups. Risk factors include the sex and number of sexual
      partners, minimal use of protected sexual behaviours and low levels of knowledge
      of STI prevention among WSW. Importantly, marginalisation leading to poorer
      mental health and experiences of abuse can combine to influence risk taking
      including substance abuse and risky sexual behaviours. Safe-sex guidelines and
      the need to recognise the impact of sexual abuse are presented.

PMID- 16402668
TI  - HIV and increased risk of cardiovascular diseases.
AB  - Highly active antiretroviral therapy (HAART) has significantly increased the
      survival rate of patients with HIV. However, abnormalities of lipid and insulin
      metabolism have been recognised and there is an increasing prevalence of fat
      redistribution, frank diabetes and hyperlipidaemia in HIV-infected patients
      receiving HAART. Several observational studies have described associations
      between HIV infection, HAART and cardiovascular disease. The management of risk
      factors for cardiovascular disease is expected to play an important role in the
      treatment of HIV infection.

PMID- 16402669
TI  - Assisted reproduction for HIV-infected couples.
AB  - Many HIV-infected individuals are in relationships with HIV-uninfected partners
      and desire to have children. This review focuses on the issue of reproductive
      choices for these couples, in particular assisted reproductive technologies, and
      summarises the published outcome data currently available. The results thus far
      from assisted reproductive technologies in optimising pregnancy outcomes and
      reducing heterosexual and perinatal HIV transmission are promising. In the
      future, it is essential that there is ongoing reporting of outcome data,
      publication of methodology and follow-up, and reporting of adverse outcomes.

PMID- 16402670
TI  - Sexually transmitted infections, blood-borne viruses and risk behaviour in an
      Australian senior high school population--the SHLiRP study.
AB  - OBJECTIVES: To determine the feasibility and acceptability of screening for
      sexually transmitted infections and blood-borne viruses and to study the profile
      of sexual activity and other risk behaviours in a senior high school population.
      METHODS: In this descriptive study we provided sexual health education and
      screening to students from two senior high schools in the Australian Capital
      Territory. We collected behavioural data using a self-administered questionnaire.
      Urines and swabs were tested for Chlamydia trachomatis (Ct), Neisseria gonorrhoea
      (Ng), Trichomonas vaginalis (Tv) and human papilloma virus (HPV). Blood specimens
      were tested for hepatitis B and C, HIV, herpes simplex viruses (HSV-1 and HSV-2)
      and syphilis. RESULTS: A total of 795 students participated (31% of the enrolled
      population; female to male ratio 60:40) and 67.0% were sexually active. Of 795
      students, 644 (81.0%) were screened. Rates of infection were Ct 1.1% (95% CI: 0.4
      2.6), HPV 11.7% (95% CI: 7.4-17.3), HSV-1 32.5% (95% CI: 28.9-36.3), HSV-2 2.4%
      (95% CI: 1.3-3.9), hepatitis B surface antigen 0.3% (95% CI: 0.04-1.1) and
      hepatitis C antibodies 0.7% (95% CI: 0.07-1.6). Only 22.3% (95% CI: 19.3-25.7) of
      students had immunity to hepatitis B. There were no cases of HIV, gonorrhoea,
      trichomoniasis or syphilis. Of the sexually active students, 49.2% (95% CI: 38.9
      59.2%) reported never or only sometimes using condoms, 41.5% (95% CI: 32.2-52.3%)
      reported unsafe drinking, 33.3% (95% CI: 23.9-43.1%) were smokers and 1.9% (95%
      CI: 0.2-7.0%) reported injecting drug use. CONCLUSIONS: Rates of STI and blood
      borne viruses and immunity to hepatitis B were low in this population, but unsafe
      sex and other risk behaviours were common. We have demonstrated that STI
      screening, including serological testing, was well accepted in a senior high
      school population.

PMID- 16402671
TI  - Use of lemon or lime juice douches in women in Jos, Nigeria.
AB  - OBJECTIVE: To describe the use of lemon/lime juice for douching by female sex
      workers (FSWs) and family planning clients (FPCs) in Jos, Nigeria. METHOD: A
      total of 300 sexually active women comprising 200 FSWs and 100 FPCs were
      interviewed in June 2004 to determine the mode and rationale for the use of
      lemon/lime juice for sex. RESULT: Majority of the women 167/300 (55.7%, 95% CI =
      50-61%) i.e. 163/200 (81.5%, 95% CI = 75-87%) FSWs, 4/100 (4%, 95% CI = 1-10%)
      FPCs used vaginal lemon/lime douches. Lime juice was used by 105/167 (62.8%, 95%
      CI = 55-70%), lemon juice by 30/167 (18%, 95% CI = 12-25%) or a mixture by 18/167
      (10.8%, 95% CI = 7-25%). The juice was used either neat 44/167 (26%, 95% CI = 20
      34%) or diluted in water 75/167 (45%, 95% CI = 37-53%) either before or after
      sex. Nineteen per cent (32/167) found the juice painful. Over half of the women
      believed that it protected them from pregnancy and/or sexually transmitted
      infections; they did not know their HIV status. Eighty-six per cent would
      recommend it to others, and 71% would be willing to take part in a study to
      evaluate its safety and efficacy. CONCLUSION: Lemon and lime juice are widely
      used for douches among women at high risk of HIV transmission. There is an urgent
      need to determine whether or not this practice promotes or prevents HIV
      infection.

PMID- 16402672
TI  - Introduction of screening guidelines for men who have sex with men at an STD
      clinic, the Melbourne Sexual Health Centre, Australia.
AB  - BACKGROUND: A recent audit indicated that a substantial proportion of men who
      have sex with men (MSM) were not screened for rectal gonorrhoea and chlamydia at
      the Melbourne Sexual Health Clinic, Melbourne, Australia. In response, screening
      guidelines for MSM were introduced at the clinic using a computer reminder. The
      aim of this study was to evaluate the impact of the guidelines and alert on
      screening MSM for gonorrhoea and chlamydia. METHODS: The medical records of MSM
      were reviewed for gonorrhoea and chlamydia screening by site (pharyngeal,
      urethral and rectal), four months before the implementation of the guidelines and
      alert (July to October 2002), and one year thereafter (beginning November 2002).
      RESULTS: After the introduction of the guidelines there was a significant
      increase in rectal chlamydia testing (55% to 67%, P < 0.001), and significant
      reduction in pharyngeal chlamydia and gonorrhoea testing (65% to 28%, P < 0.001,
      and 83% to 76%, P = 0.015 respectively). The proportion of tests that were
      positive by any site did not change (7% to 7%). CONCLUSIONS: The introduction of
      a computer reminder for new guidelines was temporally associated with screening
      that conformed more closely to clinical guidelines.

PMID- 16402673
TI  - HIV testing in an urgent-care clinic.
AB  - BACKGROUND: Early detection of HIV is increasingly important in light of advances
      in HIV research and treatment. Although treatment advances offer the potential to
      curtail HIV incidence and seroprevalence, the full benefits remain unrealised
      because many infected individuals remain unaware of their serostatus. An
      intensive observational study of HIV testing and counselling was undertaken in a
      large health maintenance organisation's urgent-care clinic (UCC) for non
      threatening illnesses and non-traumatic injuries in order to better understand
      the HIV testing process in a medical setting. METHODS: Multiple data collection
      strategies, including observation, semi-structured interviews and document and
      policy analyses, were used in order to identify key factors influencing HIV
      testing. The study examined physicians', nurses' and physician's assistants'
      relationships with patients in the UCC. RESULTS: It was found that HIV testing in
      the UCC is highly variable because some patients are asked about their sexual
      risk histories and given HIV prevention education materials and others are not.
      Moreover, for those patients who do receive these components of testing, the
      content of both the risk assessments and HIV prevention counselling varies from
      patient to patient. Findings also highlight the problematic nature of providing
      HIV test results in an UCC. CONCLUSIONS: A number of implementation issues were
      found to be relevant to the new US Centers for Disease Control and Prevention
      (CDC) policy of making HIV testing a routine feature of medical care. The study
      results suggest the need for organisationally fine-tuned interventions designed
      to improve the process of testing patients for HIV in medical settings.

PMID- 16402674
TI  - Changes in testing methods for genital Chlamydia trachomatis in New South Wales,
      Australia, 1999 to 2002.
AB  - BACKGROUND: Over the last decade, significant advances have occurred in the area
      of chlamydia diagnostics. The relative frequency of different testing methods
      employed in the diagnosis of Chlamydia trachomatis infection in New South Wales
      has not been previously reported. METHODS: Testing methods--both laboratory
      method and specimen type--employed in the diagnosis of chlamydia cases notified
      in New South Wales between 1999 and 2002 were collated from Health Department
      records. RESULTS: During a period of increasing notifications, the proportion of
      men diagnosed with C. trachomatis using nucleic acid tests (NATs) increased from
      36% in 1999 to 90% in 2002. Among women, the proportion diagnosed using NATs
      increased from 42% in 1999 to 92% in 2002. Urine samples were consistently used
      in the diagnosis of two-thirds of the men, and one-third of the women.
      CONCLUSION: Between 1999 and 2002, a rapid shift towards NATs for genital C.
      trachomatis took place in New South Wales.

PMID- 16402675
TI  - An audit of contact tracing for cases of chlamydia in the Australian Capital
      Territory.
AB  - BACKGROUND: Contact tracing is one of the central pillars of the management of
      sexually transmitted infections. The aims of this audit were to determine the
      yield of chlamydia infection from contact tracing the sexual partners of
      individuals diagnosed with chlamydia and to evaluate and compare the
      effectiveness of contact tracing undertaken at the Communicable Diseases Control
      Section (CDCS) of Australian Capital Territory (ACT) Health and the Canberra
      Sexual Health Centre (the clinic). METHODS: A retrospective review of the
      notification records and contact-tracing documentation was undertaken at CDCS and
      the clinic from 1 September 2002 to 30 September 2003 (13 months). RESULTS: The
      background rate of chlamydia in those tested in the ACT community is 3-5%. During
      the study period, 512 cases of chlamydia were notified to CDCS. Of these, 351
      were referred for contact tracing, 293 by CDCS and 98 by the clinic. Of the 437
      nominated sexual contacts (average of 1.12 per index case), 272 (62.2%) were
      contacted, 125 (28.6%) were tested and 51 (11.7%; 95% CI 8.8-15.1) tested
      positive for chlamydia (15.5%; 95% CI 11.5-20.6% in sexual contacts of CDCS index
      cases and 7.8%; 95% CI 4.8-12.5% in those of the clinic patients). Contact
      tracing through the CDCS reached significantly more nominated sexual contacts
      (78.4% v. 41.7%; P = 0.001) and significantly more of the nominated sexual
      contacts of index cases reported to CDCS were described as tested (34.7% v.
      20.8%; P = 0.01). The average time taken to identify each chlamydia-positive
      sexual contact was 6.8 hours. CONCLUSIONS: Contact tracing more than doubled the
      case finding effectiveness of chlamydia screening, but was time consuming. These
      results suggest that provider-initiated contact tracing has clinical and public
      health value, but that the cost-effectiveness of this approach to chlamydia
      control should be further evaluated.

PMID- 16402676
TI  - Do all women attending urban sexual health services need testing for gonorrhoea?
AB  - Asymptomatic women are often screened for gonorrhoea at Australian sexual health
      centres. The medical records of all women diagnosed with gonorrhoea at the
      Melbourne Sexual Health Centre (MSHC) between January 2002 and December 2003 were
      audited and the database was examined for risk factors in all women tested in
      2003. Fifteen cases of gonorrhoea were identified among women at MSHC, all had
      symptoms or an identifiable risk factor. Asymptomatic women without risk factors
      may not require screening for Neisseria gonorrhoeae in low prevalence
      populations.

PMID- 16402677
TI  - Bacterial vaginosis in female sex workers in Chennai, India.
AB  - Bacterial vaginosis (BV) causes obstetric and gynaecological complications and
      non-chlamydial/non-gonococcal pelvic inflammatory disease and has been shown to
      be associated with the risk of acquiring HIV and herpes simplex (HSV)-2
      infections. This study investigated both the prevalence of BV and its association
      with STDs among 582 female sex workers living in Chennai, South India. Blood,
      vaginal and endocervical swabs were tested for HSV-2, HIV, Treponema pallidum,
      BV, Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis. The
      vaginal swabs collected were Gram's stained and analysed for BV by Nugent's
      scoring criteria. Of the women studied, 45% (95% CI, 40.6-48.7) were positive,
      39.5% (95% CI, 35.5-43.5) were negative and 16% (95% CI, 12.8-18.7) were
      intermediate for BV. Bacterial vaginosis positivity was directly related to
      concurrent infection with HSV-2 (RR 1.3, AR 12, P = 0.00), T vaginalis (RR 1.5,
      AR 10, P = 0.01) T. pallidum (RR 2.8, AR 16, P = 0.00) and HIV (RR 4.1, AR 52, P
      = 0.01). Future studies are needed to focus on the risk factors for BV.

PMID- 16402678
TI  - Hepatitis D.
AB  - Hepatitis D virus (HDV) is a small, RNA-containing virus that requires the
      concomitant presence of Hepatitis B virus (HBV) in an obligate manner for its
      survival and pathogenicity. HDV infection is very uncommon in Czech Republic. The
      results of antiviral therapy of hepatitis D patients are not satisfactory. Alpha
      interferon (alpha-IFN) in high doses (9-10 MU three times a week for 12 months)
      is usually recommended.

PMID- 16402679
TI  - Inhibition of Measles virus multiplication in cell culture by RNA interference.
AB  - Measles takes a toll of one million people a year worldwide, especially in
      developing countries. As the so far applied vaccines were not able to control
      this disease, novel approaches to this problem are needed. In this study, we
      investigated the possibility of inhibition of Measles virus (MV) infection
      through RNA interference (RNAi), namely the interference with the second but main
      receptor of MV, signaling lymphocyte activation molecule (SLAM), in an Epstein
      Barr virus (EBV)-transformed marmoset B cell line B95-8. Three potential target
      sequences in the SLAM gene were chosen and cloned into the pSilencer 3.0-H1
      vector. The vector constructs were used for transfection of B95-8 cells in which
      SLAM was then detected by flow cytometry, Western blot analysis and RT-PCR both
      at transcription and expression levels. One of the vector constructs was found to
      block effectively the SLAM expression as well as MV infection. These results
      suggest that RNAi could silence SLAM expression and inhibit the MV infection of
      host cells.

PMID- 16402680
TI  - Inhibition of hepatitis B virus replication by recombinant small interfering
      RNAs.
AB  - RNA interference (RNAi) is a biological phenomenon in which introduction of a
      small, double-stranded interfering RNAs (siRNAs) into a cell causes a specific
      degradation of homologous single-stranded RNA. siRNA can be delivered into the
      cell by different approaches including synthetic RNA, in vitro transcribed RNA
      and RNA transcribed from polymerase III-based recombinant vectors. As hepatitis B
      (HB) represents a worldwide health problem, we attempted to develop a fast and
      easy approach to generation and screening of specific siRNA-targeted HB virus
      (HBV) genes. Using PCR amplification, specific siRNA expression cassettes (SECs)
      were developed and used to generate effective siRNAs against HB virus (HBV)
      replication and gene expression in mammalian cells. After screening, we
      identified two SECs that expressed siRNAs which efficiently decreased the level
      of HBV pre-c/c gene expression in transfected Bel-7402 cells by 81.9% and 87.3%,
      respectively. In addition, the level of HBV DNA was decreased by 83.5% and 85.2%
      in HepG2 2.2.15 cells, respectively. This study provides (i) a new effective
      application of RNA interference to study viral gene function and viral
      replication and (ii) a new tool for the prevention and treatment of human HBV
      infection.

PMID- 16402681
TI  - Differences in antibody responses of mice to intranasal or intraperitoneal
      immunization with influenza A virus and vaccination with subunit influenza
      vaccine.
AB  - Two antigenically related but different influenza A virus strains of H3N2
      subtype, A/Dunedin/ 4/73 (H3N2) (Dunedin) and A/Mississippi/1/85 (H3N2)
      (Mississippi), were used for intranasal (i.n.) and intraperitoneal (i.p.)
      immunization of mice and respective antibody responses were compared. In ELISA,
      using purified influenza A virus as antigen, the highest titer of antiviral
      antibodies was observed after a repeated i.n. infection, in which the Dunedin
      strain was followed by the Mississippi strain and vice versa. Similarly, in virus
      neutralization (VN) test, the highest titer of VN antibodies was found after a
      repeated i.n. infection. The subunit vaccine INFLUVAC, when administered
      intramuscularly (i.m.), induced only a poor antibody response as assayed by
      ELISA. Moreover, the INFLUVAC vaccination elicited a 100-fold lower titer of VN
      antibodies than the i.n. infection and an approx a 10-fold lower titer than the
      i.p. immunization. A repeated INFLUVAC vaccination did not lead to a significant
      increase of VN antibody titer. Also the antibody response to HA2gp--a conserved
      part of influenza hemagglutinin (HA) that might contribute to the induction of
      specific antiviral antibodies--was followed. Similarly to the VN antibody
      response, the highest HA2 antibody titer was induced after a repeated i.n.
      infection, whereas the lowest HA2 antibody titer was observed after a single or
      repeated INFLUVAC vaccination. Overall, the HA2 antibody titers remarkably well
      corresponded to the VN potential of the examined sera.

PMID- 16402682
TI  - Effect of metal complexes of acyclovir and its acetylated derivative on Herpes
      simplex virus 1 and Herpes simplex virus 2 replication.
AB  - The effect of zinc, nickel, cobalt and cadmium complexes of acyclovir (ACV) and
      its omicron-acetylated derivative (Ac-ACV) on the replication of wild type (wt)
      and ACV-resistant (ACV(R)) strains of Herpes simplex virus 1 (HSV-1) and Herpes
      simplex virus 2 (HSV-2) was examined. According to cytotoxicity, these compounds
      followed the order Ni-ACV chloride > Cd-ACV 3 Ni-ACV nitrate > ACV = Zn-ACV
      nitrate = Ac-ACV = Zn-Ac-ACV > Zn-ACV chloride > Co-ACV. Besides Ac-ACV, the only
      active complexes in inhibiting virus replication were Zn-ACV nitrate and Zn-Ac
      ACV, which effectively suppressed the growth of both wt and ACVR strains of HSV-1
      and HSV-2. The most active and most selective inhibitor of the growth of ACVR
      strains of HSV-1 and HSV-2 was Ac-ACV; its EC50 and SI were 100 and 10 times
      higher than those of ACV, respectively. Zn-Ac-ACV was less active than Ac-ACV,
      obviously due to the stability of the complex. Zn-ACV nitrate was active against
      both wt and ACVR strains of HSV-1; its activity and selectivity were 100 and 75
      times higher than those of ACV, respectively. Ac-ACV and Zn-Ac-ACV suppressed the
      pre-mitotic arrest caused by HSV-1 infection during the first 2 hrs of infection
      and later on restored the cell division.

PMID- 16402683
TI  - Analysis of specificity of interaction between synthetic key saccharide
      components of lipopolysaccharides and monoclonal antibodies to Coxiella burnetii.
AB  - Two monoclonal antibodies (MAbs) against the lipopolysaccharides (LPSs) of
      Coxiella burnetii (C.b.) strains Priscilla and Nine Mile were prepared
      characterized by their interaction with synthetic glycoconjugates representing
      parts of LPSs of C.b. in virulent phase. Both MAbs were directed against
      immunodominant epitopes comprising core constituent of LPSs, Kdo (3-deoxy-alpha-D
      manno-2-octulo-pyranosylonic acid). ELISA showed that the anti-Nine Mile MAb 4/11
      bound preferably to disaccharides (alpha-Kdo (2 --> 4) alpha-Kdo and alpha-Kdo (2
      --> 4) alpha-(5d) Kdo), while the anti-Priscilla MAb 1/4/H bound to all
      conjugates, though with various intensity. On the other hand, immunoelectron
      microscopy revealed a positive binding of only one glycoconjugate, namely the
      trisaccharide alpha-Kdo (2 --> 4) alpha-Kdo (2 --> 4) alpha-Kdo-BSA, to both
      MAbs. In competitive ELISA (cELISA), the anti-Priscilla MAb 1/4/H distinguished
      the strains Nine Mile and Priscilla, while the anti Nine Mile MAb 4/11 did not.

PMID- 16402684
TI  - Complete nucleotide sequence of Radish mosaic virus RNA polymerase gene and
      phylogenetic relationships in the genus Comovirus.
AB  - The 3'-terminal part of RNA1 genome segment of Radish mosaic virus (RaMV)
      including complete RNA polymerase gene was sequenced. The 207 amino acids long
      polymerase is matured from a polyprotein precursor by cleavage at putative Q/H
      site by viral protease. The alignment of available amino acid sequences of RNA
      polymerase genes of comoviruses revealed a closest (55%) identity of RaMV to Red
      clover mottle virus (RCMV).

PMID- 16402685
TI  - Characterization of the hemagglutinin and neuraminidase genes of recent influenza
      virus isolates from different avian species in Thailand.
AB  - The hemagglutinin (HA) and neuraminidase (NA) genes of eight influenza A virus
      (H5N1) isolates obtained from various avian species in Thailand in 2003-2004 have
      been characterized in comparison with the Thai isolate A/Chicken/Nakorn
      Pathom/Thailand/CU-K2/04(H5N1). Phylogenetic analyses of both genes revealed that
      all the eight avian isolates were closely related to the A/Chicken/Nakorn
      Pathom/Thailand/CU-K2/ 04(H5N1). The amino acid sequence of the HA cleavage site
      revealed a common characteristic of a highly pathogenic virus strain. Moreover, a
      deletion of 20 amino acids in the NA stalk region was detected in all Thai
      isolates in contrast to the H5N1 strain that had caused outbreaks in eastern Asia
      in 1996-1997 and 2000-2001.

PMID- 16402686
TI  - Seromonitoring of Newcastle disease--a field study.

PMID- 16402687
TI  - Cytokine profiles in peripheral blood mononuclear cells and sera from patients
      with acute self-limited hepatitis A.

PMID- 16402688
TI  - Genomic diversity of Indian isolates of bluetongue virus.

PMID- 16402689
TI  - Detection of an influenza virus in wild waterbirds migrating through Slovakia in
      autumn 2004.

PMID- 16402690
TI  - [Are miracles possible?].

PMID- 16402691
TI  - [God does not let himself be instrumented (interview by Dr. Peter Stiefelhagen)].

PMID- 16402692
TI  - [A lazy patient--or is there more to the symptom?].

PMID- 16402693
TI  - [How does that fit together?].

PMID- 16402694
TI  - [Turning back the clock still one more time].

PMID- 16402695
TI  - [Fish oil and statins have a synergistic action].

PMID- 16402696
TI  - [The suffering of virtuoso bodies].

PMID- 16402697
TI  - [Ballet is more than learning steps (interview by Friederike Klein)].

PMID- 16402698
TI  - [How reliable is medical care on ocean vessels? (interview by Dr. Erik Heintz)].

PMID- 16402699
TI  - [Another risk factor: gamma-GT predicts fatal outcome].

PMID- 16402700
TI  - [Antihypertensive therapy: campaign of the giants].

PMID- 16402701
TI  - [This premature infant has no chance]].

PMID- 16402702
TI  - [Chronic polyarthritis: erosions are reversible].

PMID- 16402703
TI  - [Fatal headache from breast cancer].

PMID- 16402704
TI  - [Optimizing therapy in Paget disease].

PMID- 16402705
TI  - [Diabetes in treatment with antipsychotic drugs: who is at risk]].

PMID- 16402706
TI  - [Was it the steak?].

PMID- 16402707
TI  - [Movement is the key to healing and prevention].

PMID- 16402708
TI  - [Diagnosis of chronic venous insufficiency].
AB  - While the importance of clinical criteria for the diagnosis of chronic venous
      insufficiency remains unchallenged, the equipment-based diagnosis has developed
      away from pressure measurement, plethysmography and phlebography towards Doppler
      and color-flow duplex scanning. The CEAP classification of clinical stages is
      recognized throughout the world. Skin tests, the evaluation of ankle joint
      mobility and the investigation of the thrombophilia risk continue to be required.

PMID- 16402709
TI  - [Ulcus cruris venosum--therapeutic principles].
AB  - An essential element in the management of ulcus cruris venosum is the treatment
      of the cause applying compression. For this purposes, various systems are
      currently available, the application of which, however, must always be undertaken
      with consideration being given to the individual situation and possible
      contraindications. Topical treatment of chronic wounds, including ulcus cruris
      venosum, is performed stage-oriented, in accordance with the principles of moist
      wound care. The critical selection of the most appropriate dressing materials for
      the case presenting is essential for a treatment that is both medically and
      economically justifiable. An aim of the treatment continues to be the curtailment
      of the still too long treatment times, and to reduce the number of recurrences.

PMID- 16402710
TI  - [Physical exercise in thte treatment of ulcus cruris venosum].
AB  - As an adjuvant measure, physical exercise should be recommended for all patients
      with an ulcus cruris venosum, and should be a permanent part of the patient's
      lifestyle on completion of wound healing. Although clinical studies have shown
      that physical exercise has a positive effect on numerous factors of relevance for
      the development of an ulcer, sports activities undertaken for therapeutic and
      prophylactic purposes are still made little use of by patients.

PMID- 16402711
TI  - [Toxic mustard plaster dematitis and phototoxic dematitis after application of
      bergamot oil].
AB  - Two cases that illustrate the risks attendant on the therapeutic use of natural
      medications by laypersons are reported. In the first case, the application of a
      mustard plaster triggered toxic dermatitis. In the second case, a session in a
      solarium after the external application of bergamot oil resulted in a phototoxic
      reaction.

PMID- 16402712
TI  - [Organizational committee shines with incompetence].

PMID- 16402713
TI  - [Treating with what? Therapy for how long?].

PMID- 16402714
TI  - [Reliably combined to combat osteoporosis].

PMID- 16402715
TI  - [Physician deficit crumbles preventative care for the elderly].

PMID- 16402716
TI  - [General practice group favors resistance].

PMID- 16402717
TI  - [Genotype 1 superresponder treat for only 24 weeks].

PMID- 16402718
TI  - [Revised blood pressure goals and no elevated glucose readings in between].

PMID- 16402719
TI  - [Reliably pain free with a new fentanyl patch].

PMID- 16402720
TI  - [Simple to use--superior adhesiveness].

PMID- 16402721
TI  - [Pharaohs in good hands].

PMID- 16402722
TI  - [Small adenoma--big effect].

PMID- 16402723
TI  - [Consensus-based guidelines on prostate biopsy].
AB  - OBJECTIVE: To develop evidence-based and consensus-based guidelines, helping
      physicians to take decisions about diagnostic procedures for men wishing to
      undergo examination for detection of prostate cancer. MATERIAL AND METHODS: A
      panel of multidisciplinary Italian experts in urology, medical oncology,
      laboratory medicine, radiotherapy, pathology and methodologists for clinical
      trial (Mario Negri Institution) grouped together in 2002 to address specific
      questions relating to clinical controversies in prostate cancer diagnosis. A
      practitioners feedback survey by means of a questionnaire of 49 items was also
      conducted in 2003 to assess the great variability in all the aspects relating a
      prostate biopsy (PB). Experts reviewed relevant evidence, using CeVEAS scale, of
      the literature from 1966 to December 2004 (Medline, Embase, Cochrane library)
      before offering the discussion panel proposed guidelines for a given subset of
      questions. The discussion panel, which consisted of presenters and
      representatives from medical oncology, forensic medicine, radiotherapy, ethics,
      biochemistry and family practice medicine, took place on February 12, 2005 in
      Bologna. The panel deliberated to reach consensus on suggested guidelines. When
      evidence was insufficient, suggested guidelines represent the opinion of a cross
      section of the presenters and discussion panel. RESULTS: Consensus was achieved
      regarding all the aspects relating PB. The final paper was approved by the jury,
      the panel of experts and the audience. A standardized guideline, containing a
      short version for physicians and a standardized patient information booklet, for
      nation-wide use was developed. In the final document it has been reported as
      following: Prostatic biopsy (PB) is recommended in all patients with a PSA> = 4.0
      ng/ml (2,5 ng/ml in patients with positive family history), abnormal DRE and
      %FPSA < 10%. PSAD and PSAV are considered controversial predictive factors.
      Antibiotic prophylaxis with a fluoroquinolone, which can be omitted in cases of
      transperineal (TP) PB, is mandatory when using a transrectal (TR) approach. It is
      necessary to start the prophylaxis the day before and continued for 2-3 days
      after the procedure. Anaesthesia is mandatory in case of TP biopsy and strongly
      recommended in cases of TR PB (10 cc of periprostatic lidocaine injection rather
      than intrarectal lidocaine gel). The optimal PB scheme should include more than 6
      cores (preferably 10-12 cores) weighted more laterally and apically. PB directed
      only to the hypoechoic lesion or standard sextant biopsy (Hodge's scheme) are
      considered obsolete. PB of the transition zone are mandatory only in cases of re
      biopsy. A tru-cut needle with a diameter of 18 Fr. is recommended and a sandwich
      technique for core fixation informalin is considered the optimal approach. A PB
      should be repeated within 6-12 months in the following cases:1) First biopsy is
      inadequate (less than 6 cores, absence of prostatic cells on the cores), 2) in
      presence of HGPIN, ASAP or both on first PB, 3) in cases with persistently high
      levels of PSA (PSA > 10 ng/ml or PSA velocity > 0,75 ng/ml/year). PB after
      radiotherapy is not routinely indicated as well as biopsy of the vesico-urethral
      anastomosis after radical prostatectomy in patients with PSA failure.
      CONCLUSIONS: The suggested guidelines represent a reasonable diagnostic approach
      in patients to be submitted to PB, with the understanding that new data,
      subsequent findings, or other methodological considerations may lead to future
      modifications.

PMID- 16402724
TI  - [When to carry out prostate biopsy].

PMID- 16402725
TI  - [Prostate biopsy: patient preparation and anesthesia].

PMID- 16402726
TI  - [Prostate biopsy: approaches].

PMID- 16402727
TI  - [Prostate biopsy: characteristics of the histological sample].

PMID- 16402728
TI  - [Prostate biopsy: number and places of sampling].

PMID- 16402729
TI  - [Prostate biopsy: re-biopsy after first negative biopsy].

PMID- 16402730
TI  - [Prostate biopsy: re-biopsy after radiotherapy].

PMID- 16402731
TI  - [Prostate biopsy: re-biopsy after prostatectomy].

PMID- 16402732
TI  - [Prostate biopsy: staging values].

PMID- 16402733
TI  - [Guidelines for prostate biopsy].

PMID- 16402734
TI  - Struggling to regain normalcy: LSUHSC after Hurricane Katrina.

PMID- 16402735
TI  - Kuwaiti high school students' perceptions of nursing as a profession:
      implications for nursing education and practice.
AB  - The shortage of nurses in Kuwait is attributed to low production of indigenous
      nurses, resignation and emigration of foreign nurses, and expansion of health
      care facilities. This study explored Kuwaiti high school students' perceptions of
      nursing as a profession, their sources of information about nursing, and factors
      that affected their choice of nursing as a future career. Questionnaires from 289
      students attending seven all-female high schools in Kuwait were analyzed. The
      results revealed that all of the participants were knowledgeable about the
      functional aspects of the nursing profession, and 35% of them received this
      information through contact with nurses during hospital visits. However, only 19%
      indicated they might consider nursing as a future career. The implications of the
      study for nursing education and practice, and strategies to attract and retain
      indigenous high school graduates into nursing programs in Kuwait are discussed.

PMID- 16402736
TI  - Strategies for lowering attrition rates and raising NCLEX-RN pass rates.
AB  - This study was designed to determine strategies to raise the NCLEX-RN pass rate
      and lower the attrition rate in a community college nursing program. Ex-post
      facto data were collected from 213 former nursing student records. Qualitative
      data were collected from 10 full-time faculty, 30 new graduates, and 45 directors
      of associate degree nursing programs in Texas. The findings linked the academic
      variables of two biology courses and three components of the preadmission test to
      completion of the nursing program. A relationship was found between one biology
      course, the science component of the preadmission test, the HESI Exit Examination
      score, and the nursing skills course to passing the NCLEX-RN. Qualitative data
      indicated preadmission requirements, campus counselors, remediation, faculty,
      test-item writing, and teaching method were instrumental in completion of the
      program and passing the NCLEX-RN.

PMID- 16402737
TI  - Professional resilience, practice longevity, and Parse's theory for baccalaureate
      education.
AB  - New nurses seem unable to find a means of flourishing professionally in acute
      care practice and, consequently, exit far earlier than expected. Worldviews of
      baccalaureate students have changed from previous generations; yet, the
      approaches to nursing education remain essentially the same. Just as clinical
      settings benefit from nursing theory as the basis for nursing practice and
      scientific inquiry, the science of nursing education would benefit from nursing
      theory as a basis for guiding educational practice. Parse's human science theory,
      the Human Becoming School of Thought, is a fitting theoretical framework for a
      model of teaching-learning for undergraduate baccalaureate nursing education. In
      addition, as a theory of dynamic relational synchrony, Parse's work provides an
      appropriate framework with which to promote professional resilience and career
      longevity by purposefully engaging students within student-faculty dyads to
      explore personal meanings and philosophies of caring, and to create strong
      professional identities.

PMID- 16402738
TI  - California's minority majority and the White face of nursing.
AB  - Of the 33 million people in California, the nation's most populous state,
      minority groups now constitute the majority of the population. Many sources
      predict that by 2060, the entire country will mirror the diversity of California
      today. Like the rest of the country, California is experiencing a critical
      shortage of nurses that is predicted to increase in the coming years, and
      California's nursing workforce does not represent the racial and ethnic diversity
      of the state's population as a whole. If the nursing profession is to thrive in
      the coming years, educators and leaders must create a way to embrace people from
      diverse ethnicities and cultures. The purposes of this article are to determine
      whether ethnic minority groups have different success rates in California nursing
      programs, whether nursing programs with high percentages of diverse students have
      differing success rates, and to describe the institutional predictors of on-time
      completion rates, attrition rates, and NCLEX-RN first-time pass rates in
      California community colleges.

PMID- 16402739
TI  - A preliminary study of a healthy-lifestyle-promoting program for nursing students
      in Taiwan.
AB  - This pilot study evaluated the effects of a healthy-lifestyle-promoting program,
      taught as part of an undergraduate community health nursing course, on the
      physical fitness and health choices of 42 Taiwanese nursing students. A
      convenience sample provided quantitative indexes of physical fitness and
      lifestyle before and after the course. Qualitative data, in the form of student
      diaries, were also analyzed. The findings indicated a positive change in physical
      fitness, exercise, and nutrition as a result of the program. Including lifestyle
      programs in nursing education may help promote the long-term health of future
      nurses who will serve as positive patient role models.

PMID- 16402740
TI  - A successful Minority Retention Project.
AB  - Racial and ethnic minorities are underrepresented in the nursing profession. The
      high attrition rate of minority students from nursing schools contributes to this
      problem. Academic leaders are calling for change in nursing education and asking
      educators to work diligently to retain minority students. This article describes
      a Minority Retention Project that included interventions designed to enhance the
      integration of minority students into a supportive learning environment, assist
      them in using the available resources, and help them feel connected and supported
      by their peers and faculty. At the end of the first year of the project, the
      nursing school experienced 100% retention of minority nursing students.
      Increasing the retention and graduation of minority nursing students supports the
      continued effort to provide culturally competent health care.

PMID- 16402741
TI  - Growing nurse leaders: an undergraduate teaching assistant program.
AB  - In today's complex health care system, leader behaviors are critical for all
      nurses. The undergraduate teaching assistant (TA) program empowers students to
      develop leadership behaviors through a collaborative mentoring model. This
      successful program enables undergraduate students to collaborate with faculty and
      graduate TAs in co-teaching large classes. The collaborative mentoring,
      structured class, and ongoing support provide fertile ground for growing nurse
      leaders.

PMID- 16402742
TI  - Medication evaluation teaching strategy.

PMID- 16402743
TI  - Teaching students to use an online index.

PMID- 16402744
TI  - Event-related potentials indicate that reality monitoring differs from external
      source monitoring.
AB  - This experiment investigated differences in event-related potentials (ERPs)
      observed in 2 types of source monitoring decisions. Participants discriminated
      between self-generated, heard, and new words (reality monitoring) in one
      condition; in another they discriminated between words heard in a male or female
      voice and new items (external source monitoring). The data support the source
      monitoring framework, which argues that reality monitoring discriminations differ
      from external source monitoring discriminations. Analysis revealed better overall
      source accuracy during reality monitoring than during external source monitoring.
      In the external source monitoring task, an early old-new ERP difference was
      observed at parietal electrodes followed by frontal old-new effect that persisted
      longer, replicating previous ERP results. However, early ERP amplitude
      differences between sources were observed at parietal electrode sites during
      reality monitoring, suggesting that self-generated items activate more
      differentiated information during remembering. Furthermore, there were no frontal
      old-new ERP differences during reality monitoring, suggesting that different
      decision processes are used in these types of source monitoring decisions.

PMID- 16402745
TI  - Memory retrieval tasks determine the serial position curves of linear orders with
      categorical structures.
AB  - I examined 2 different views on organization of linear order information in
      memory: the linear schema view and the hierarchical structure view. The linear
      schema view holds that there is a strong tendency in memory to organize an array
      of transitively related elements into a unidimensional order. The hierarchical
      structure view maintains that the transitively related elements are organized in
      memory in a hierarchy of items. I proposed an input structure and retrieval
      compatibility hypothesis as a coherent explanation for the contradictory views on
      the memory organization of serial elements. I argue that the organization of
      linear order information in memory is determined by the nature of the memory
      retrieval task used. For example, a comparative judgment task is more compatible
      with a unidimensional structure, whereas a sequential recall or serial position
      identification task is more compatible with a hierarchical organization. The
      input structure and retrieval compatibility concept can also explain why
      dichotomous categories imposed on a linear order play very little role in
      comparative judgments.

PMID- 16402746
TI  - Musical stem completion: humming that note.
AB  - This study looked at how people store and retrieve tonal music explicitly and
      implicitly using a production task. Participants completed an implicit task (tune
      stem completion) followed by an explicit task (cued recall). The tasks were
      identical except for the instructions at test time. They listened to tunes and
      were then presented with tune stems from previously heard tunes and novel tunes.
      For the implicit task, they were asked to sing a note they thought would come
      next musically. For the explicit task, they were asked to sing the note they
      remembered as coming next. Experiment 1 found that people correctly completed
      significantly more old stems than new stems. Experiment 2 investigated the
      characteristics of music that fuel retrieval by varying a surface feature of the
      tune (same timbre or different timbre) from study to test and the encoding task
      (semantic or nonsemantic). Although we did not find that implicit and explicit
      memory for music were significantly dissociated for levels of processing, we did
      find that surface features of music affect semanticjudgments and subsequent
      explicit retrieval.

PMID- 16402747
TI  - Strategies for verifying false autobiographical memories.
AB  - This study examined the types of strategies people use to verify putative
      childhood memories and the degree to which their preferred strategies are
      restricted in typical memory implantation studies. We asked subjects to describe
      a situation in which they recalled a false childhood experience and a
      hypothetical situation in which they pretended to have developed a false memory
      after taking part in a memory implantation study. We also asked them how they did
      (or would) determine the source of the event. We found that subjects relied
      primarily on other people and cognitive strategies to verify their experiences.
      These results suggest that laboratory situations cultivate false memories in part
      because they prevent people from talking to others about the false event, which
      causes them to rely on less optimal strategies.

PMID- 16402748
TI  - Impact of learning orientation on African American children's attitudes toward
      high-achieving peers.
AB  - This study examined Ogbu's widely accepted thesis that African American students
      reject high academic achievement because they perceive its limited utility in a
      world where their upward mobility is constrained by racial discrimination.
      Boykin's psychosocial integrity model contends that Black students value high
      achievement but that discrepancies between their formative cultural experiences
      and those imposed in school lead them to reject the modes of achievement
      available in classrooms. Ninety Black children completed a measure of attitudes
      toward students who achieve via mainstream or African American cultural values.
      Participants rejected the mainstream achievers and embraced the African American
      cultural achievers. Moreover, they expected their teachers to embrace the
      mainstream achievers and reject those who achieved through high-verve behavior.
      Results suggest that Boykin's thesis is a needed refinement to Ogbu's ideas. They
      indicate that Black children may reject not high achievement but some of the
      mainstream cultural values and behaviors on which success in mainstream
      classrooms is made contingent.

PMID- 16402749
TI  - Altering Mueller-Lyer illusion magnitude using figural additions at the wing
      shaft intersections.
AB  - The Mueller-Lyer (ML) illusion has been used to study the way in which perceived
      length is affected by processes of information extraction when a visual target of
      interest (the ML shaft) is surrounded by other nontarget figural elements (inward
      or outward-turning wings). It is argued that the perception of length is computed
      in terms of the center of gravity or centroid of figural elements at the wing
      shaft intersection. The outward-turning wings shift the computational centroid
      away from the shaft end, giving rise to an erroneous overestimation of shaft
      length, while the inward-turning wings have the opposite effect. In three
      experiments, we observed that figural changes, which theoretically shifted the
      center of gravity of figural elements at the wing-shaft intersection, also
      increased or decreased the magnitude of the ML illusion.

PMID- 16402750
TI  - Guest editorial: rethinking the obsessive compulsive spectrum.

PMID- 16402751
TI  - Obsessive compulsive personality disorder and obsessive compulsive disorder:
      clinical characteristics, diagnostic difficulties, and treatment.
AB  - BACKGROUND: The overlap between obsessive compulsive personality disorder (OCPD)
      and obsessive compulsive disorder (OCD) has received increasing recognition and
      continues to be a source of much debate. With the advent of new research
      methodologies, researchers have attempted to distinguish whether OCPD and OCD are
      two distinct phenomena that can co-occur or whether they are similar, overlapping
      constructs. METHODS: MEDLINE was used to systematically review the OCPD and OCD
      literature published between 1991 and 2004. RESULTS: Using the more stringent DSM
      IV criteria, results from OCD clinical samples suggest that the majority of
      individuals with OCD (75%) do not have OCPD. Similarly, results from personality
      disorder samples suggest that the majority of individuals with OCPD (80%) do not
      have OCD. CONCLUSIONS: While there is evidence that OCD and OCPD are linked, the
      literature does not support either one as a necessary or sufficient component of
      the other.

PMID- 16402752
TI  - Recognizing and treating body dysmorphic disorder.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) is a relatively common and often
      disabling obsessive compulsive spectrum disorder that often goes unrecognized in
      clinical practice. METHODS: The present review examines the clinical features of
      BDD, its relationship to other disorders, and what is known about effective
      treatment. RESULTS: BDD consists of a distressing and impairing preoccupation
      with imagined or slight defects in appearance that can focus on any body area.
      Insight is usually poor or absent; nearly half of patients are delusional.
      Typical associated behaviors include skin picking, mirror checking, excessive
      grooming, and camouflaging. It appears that higher doses of serotonin reuptake
      inhibitors and longer treatment trials than those used for many other psychiatric
      disorders, including depression, are often needed to effectively treat BDD.
      Cognitive-behavioral therapy also appears efficacious and is currently considered
      the psychotherapy of choice for BDD. Core techniques are cognitive restructuring,
      behavioral experiments, response (ritual) prevention, and exposure. CONCLUSIONS:
      Further research is needed to minimize the underrecognition of BDD and to improve
      proper treatment. Because of the high rates of comorbidity in patients with BDD,
      treatment studies need to include subjects with co-occurring disorders and
      thereby attempt to understand how these other disorders affect treatment
      response. Finally, more research needs to address the pathophysiology of BDD (for
      example, by incorporating imaging and genetics).

PMID- 16402753
TI  - Hypochondriasis: conceptualization, treatment, and relationship to obsessive
      compulsive disorder.
AB  - BACKGROUND: Hypochondriasis (HC) involves preoccupation with fears of having a
      serious illness. The preoccupation is persistent and based on misinterpretation
      of benign bodily sensations. In response, patients often resort to frequent
      checks with doctors, of their own body, and of medical references, to reassure
      themselves of their health status. Some authors have likened HC to obsessive
      compulsive disorder (OCD) on the basis of similarities between obsessions and
      illness preoccupation and the ritualistic checking behavior observed in each
      condition. METHODS: In this article, the phenomenology of HC is discussed in
      terms of factors that account for the development and persistence of this
      disorder. Treatment that is derived from this conceptual model is also described.
      RESULTS: HC is best considered as an anxiety problem in which pathological fear
      is focused on innocuous bodily sensations and other health-relevant cues.
      CONCLUSIONS: Many of the psychological mechanisms of HC are similar to those
      present in OCD.

PMID- 16402754
TI  - Disorders characterized by poor impulse control.
AB  - BACKGROUND: Impulse Control Disorders (ICDs) are an eclectic group of conditions
      in which a person has a drive, urge, or temptation, to perform a potentially
      harmful act, or fails to resist an impulse. METHODS: Authors reviewed the current
      medical literature addressing this diverse group of disorders. RESULTS: Although
      the behaviors associated with these conditions can cause a great deal of
      suffering for patients and their families, they have remained relatively under
      researched and poorly characterized. CONCLUSIONS: Recent studies have explored
      both pharmacological and psychosocial treatments, giving rise to greater hope for
      the development of more effective treatments for these challenging disorders.

PMID- 16402756
TI  - Show me the book contract.

PMID- 16402755
TI  - Pathologic hairpulling, skin picking, and nail biting.
AB  - BACKGROUND: Pathologic hairpulling (HP), skin picking (SP), and nail biting (NB)
      are repetitive, intentionally performed behaviors that cause noticeable hair loss
      or substantial physical damage, and result in clinically significant distress or
      functional impairment. To date, HP, SP, and NB have received little attention in
      the psychiatric literature despite being widespread behaviors. METHODS: The
      present article reviews the up-to-date research findings on these three forms of
      pathologic behavior, highlighting their similarities and differences. RESULTS:
      Despite HP, pathologic grooming behaviors have not yet been explicitly included
      in the diagnostic nomenclature. Phenomenology, triggers, consequences and
      functionality of HP, SP, and NB are similar, which suggest their joint diagnostic
      categorization. Sufferers often fail to admit the self-inflicted nature of their
      physical damage out of shame and embarrassment, which complicates the recognition
      and differential diagnosis of sufferers. Thus, practitioners need to be
      particularly attentive to physical signs possibly related to these behavior
      disorders. CONCLUSIONS: Research suggests that HP, SP, and NB are underrecognized
      problems that occur on a continuum ranging from mild to severe. Further research
      is needed, especially regarding the etiology of pathologic HP, SP, and NB, to
      foster the development of both effective and long-lasting treatments and
      prevention strategies.

PMID- 16402757
TI  - Tobacco use and pathological gambling.
AB  - BACKGROUND: Evidence supports phenomenological, clinical, epidemiological and
      biological links between problem/pathological gambling and tobacco use. An
      improved understanding of the relationship would be helpful in treating
      individuals with co-occurring pathological gambling and nicotine dependence.
      METHODS: This study investigates the tobacco use behaviors of 225 adults (mean
      age +/- SD = 47.3 +/- 11.0 years; number of women = 120 [53.3%]) who were
      recruited for pharmacological treatment of pathological gambling. All subjects
      met criteria for pathological gambling based upon the Structured Clinical
      Interview for Pathological Gambling (SCI-PG), a DSM-IV-based diagnostic
      interview, and were assessed at baseline with multiple reliable and valid
      measures of gambling severity. RESULTS: 159 (70.7%) subjects were either current
      (n = 110; 48.9%) or prior daily smokers (n = 49; 21.8%). Compared with the group
      of never smokers, the group of current and prior daily smokers was more likely to
      be older (F = 3.55; df = 2, 222; p = 0.030), be female (chi square = 10.85; df =
      2; p = 0.004), and have stronger urges to gamble (F = 128.15; df = 2,222; p <
      0.001). CONCLUSIONS: Daily tobacco use in treatment-seeking pathological gamblers
      is common and associated with more severe urges to gamble. Treatments targeting
      urges in individuals with pathological gambling and current or prior daily
      tobacco use should be examined.

PMID- 16402758
TI  - Problem and pathological gambling among college athletes.
AB  - BACKGROUND: Problematic gambling is common in college students, and in
      particular, athletes. METHODS: The frequency of problem and pathological gambling
      was determined among 636 college athletes at three Midwest universities using the
      South Oaks Gambling Screen (SOGS). The Gambling Attitude Scale (GAS) was used to
      assess college athletes' attitudes toward gambling in general and toward four
      modes of gambling (casinos, betting on horse races, lottery and the Internet). A
      profile of college athletes' gambling attitudes and behavior was developed
      through the data obtained from each of these instruments. RESULTS: Nearly 15% of
      respondents had a SOGS score >or=3, indicating problem or pathological gambling.
      Those at risk for a gambling problem gambled frequently, had family and/or
      friends with perceived gambling problems, were nonwhite, older, started gambling
      at a younger age, preferred games of skill, and held positive attitudes toward
      gambling in general and Internet gambling, in particular. CONCLUSIONS: Gambling
      problems are widespread among college athletes who constitute a vulnerable group.
      Specific interventions are needed to target this group.

PMID- 16402759
TI  - Gender differences in adolescent gambling.
AB  - BACKGROUND: Although adolescent gambling has been linked to a wide array of risk
      behaviors, little is known regarding the correlates of gambling in adolescent
      girls as compared with adolescent boys. METHODS: We examined by logistic
      regression a nationally representative U.S. sample (n = 534) of 16- and 17-year
      olds from the 1998 Gambling Impact and Behavior Study (GIBS) (1) to investigate
      the influence of gender on: 1) the association between gambling and psychiatric
      symptomatology; and, 2) gambling attitudes and behaviors. RESULTS: Gambling was
      associated with elevated rates of alcohol use and abuse/dependence in both boys
      and girls, and dysphoria/depression in girls only. Boy gamblers reported heavier
      gambling and higher rates of gambling problems than did girl gamblers.
      CONCLUSIONS: Adolescent gambling may be associated with more severe psychiatric
      symptoms in girls than in boys, though future research will be needed to
      replicate and extend these findings. Gender considerations are important in
      understanding youth gambling and the relationship between gambling and
      psychiatric disorders in adolescents.

PMID- 16402760
TI  - Immediate switching of antidepressant therapy: results from a clinical trial of
      duloxetine.
AB  - BACKGROUND: Approximately half of all treated depressed patients fail to show
      adequate response to their initially prescribed antidepressant medication.
      Switching to another medication represents one possible next-step approach for
      nonresponsive or partially responsive patients. However, specific techniques for
      switching between antidepressants have not been well studied. We examined the
      efficacy and tolerability associated with a switch from a selective serotonin
      reuptake inhibitor (SSRI) or venlafaxine to duloxetine. METHODS: All patients met
      criteria for major depressive disorder as defined in DSM-IV. Patients (N = 88)
      exhibiting suboptimal response or poor tolerability to their current
      antidepressant medication (citalopram <or=40 mg/d, escitalopram <or=20 mg/d,
      fluvoxamine <or=150 mg/d, paroxetine <or=40 mg/d, sertraline <or=150 mg/d, or
      venlafaxine <or=150 mg/d) were switched to duloxetine 60 mg once-daily (QD)
      without intermediate tapering or titration ("switching" group). A comparator
      group (N = 67), comprising patients not currently receiving antidepressant
      medication, initiated duloxetine therapy at 60 mg QD ("initiating" group). Safety
      assessments included comparisons of discontinuation rates, treatment-emergent
      adverse events, and changes in vital signs. Efficacy measures included the
      HAMD(17), Hamilton Anxiety Scale (HAMA), and the Clinical Global Impression of
      Severity (CGI-S) scale. RESULTS: The efficacy of duloxetine in switched patients
      did not differ significantly from that observed in untreated patients initiating
      duloxetine therapy (mean changes: HAMD(17) total score: -12.3 vs. -12.6; HAMA: 
      9.36 vs. -9.55, CGI-S: -1.94 vs. -2.12, respectively). However, the rate of
      discontinuation due to adverse events among patients switched to duloxetine was
      significantly lower than that in patients initiating duloxetine therapy (4.5% vs.
      17.9%, p = .008). Treatment-emergent adverse events occurring in >or=10% of
      patients in both treatment groups were nausea, headache, dry mouth, insomnia, and
      diarrhea. Patients switched to duloxetine reported significantly lower rates of
      nausea and fatigue compared with patients initiating duloxetine. CONCLUSIONS: In
      this study, the efficacy of duloxetine in switched patients was comparable to
      that observed in patients initiating duloxetine therapy. Immediate switching from
      an SSRI or venlafaxine to duloxetine (60 mg QD) was well tolerated.

PMID- 16402761
TI  - A review of antioxidants and Alzheimer's disease.
AB  - BACKGROUND: In this article, we review a diverse body of research and draw
      conclusions about the usefulness, or lack there-of, of specific antioxidants in
      the prevention of Alzheimer's disease (AD). METHODS: The National Library of
      Medicine's database was searched for the years 1996-2004 using the search terms
      "Alzheimer's, anti-oxidants, antioxidants." RESULTS: Over 300 articles were
      identified and 187 articles were selected for inclusion based on relevance to the
      topic. Agents that show promise in helping prevent AD include: 1) aged garlic
      extract, 2) curcumin, 3) melatonin, 4) resveratrol, 5) Ginkgo biloba extract, 6)
      green tea, 7) vitamin C and 8) vitamin E. CONCLUSIONS: While the clinical value
      of antioxidants for the prevention of AD is often ambiguous, some can be
      recommended based upon: 1) epidemiological evidence, 2) known benefits for
      prevention of other maladies, and 3) benign nature of the substance. Long-term,
      prospective studies are recommended.

PMID- 16402770
TI  - Large aqueous aluminum hydroxide molecules.

PMID- 16402771
TI  - Recent developments in isocyanide based multicomponent reactions in applied
      chemistry.

PMID- 16402772
TI  - Cytochrome c: occurrence and functions.

PMID- 16402773
TI  - Synthesis and pharmacology of galantamine.

PMID- 16402774
TI  - Bonding and organic and inorganic reactivity of metal-coordinated
      phosphinoenolates and related functional phosphine-derived anions.

PMID- 16402775
TI  - Synthetic routes to thiooligosaccharides and thioglycopeptides.

PMID- 16402776
TI  - Polar acetalization and transacetalization in the gas phase: the Eberlin
      reaction.

PMID- 16402778
TI  - Time-resolved photodynamics of triangular-shaped silver nanoplates.
AB  - We measured the ultrafast response of triangular silver nanoparticles upon
      femtosecond excitation of their plasmon resonance. After a fast electron
      relaxation, the signature of a bimodal mechanical vibration of the particle is
      apparent as a spectral modulation. We identify the two lowest frequency, totally
      symmetric vibrations of the particle as responsible for this modulation, through
      their influence on the plasmon peak position and width, in full agreement with
      the results of a variational elastodynamic model that is also presented. From the
      analysis of the phase we conclude that thermal expansion and electron pressure,
      respectively, are responsible for the excitation of the two vibrations.

PMID- 16402777
TI  - Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe.
AB  - MRI detectable and targeted quantum dots were developed. To that aim, quantum
      dots were coated with paramagnetic and pegylated lipids, which resulted in a
      relaxivity, r(1), of nearly 2000 mM(-1)s(-1) per quantum dot. The quantum dots
      were functionalized by covalently linking alphavbeta3-specific RGD peptides, and
      the specificity was assessed and confirmed on cultured endothelial cells. The
      bimodal character, the high relaxivity, and the specificity of this
      nanoparticulate probe make it an excellent contrast agent for molecular imaging
      purposes.

PMID- 16402779
TI  - Hybrid single-nanowire photonic crystal and microresonator structures.
AB  - We report a hybrid approach for photonic systems that combines chemically
      synthesized single nanowire emitters with lithographically defined photonic
      crystal and racetrack microresonator structures. Finite-difference time-domain
      calculations were used to design nanowire photonic crystal structures where the
      photonic band gap overlaps the electronic band gap of the nanowire.
      Photoluminescence (PL) images of cadmium sulfide (CdS) nanowire photonic crystal
      structures designed in this way demonstrate localized emission from engineered
      defects and light suppression in regions of the photonic crystal. PL spectroscopy
      studies of defect-free nanowire photonic crystal structures further demonstrate
      the photonic band gap or stop band that spans most of the CdS band edge emission
      spectrum. In addition, single CdS nanowire-racetrack microresonator structures
      were fabricated, and PL imaging and spectroscopy measurements show good coupling
      of the nanowire to the microcavity including efficient feedback and amplified
      spontaneous emission. These hybrid structures exploit unique strengths of bottom
      up and top-down approaches and thereby open new opportunities in nanophotonics
      from efficient and localized light sources to integrated optical processing.

PMID- 16402780
TI  - Temperature-programmed assembly of DNA:Au nanoparticle bioconjugates.
AB  - Temperature has been used to control the order of assembly events in a solution
      containing three types of particles to be linked by two different sets of
      complementary DNA. At higher temperatures, only the duplexes having higher
      thermal stability were able to form. By starting at a high temperature and then
      cooling the sample, these more stable sequences hybridized first, followed by the
      less stable sequences at lower temperatures. Because of the use of thiolated DNA
      on Au particles, some loss and exchange of the DNA strands occurred at elevated
      temperatures. However, since cooperativity favors the "correct" assemblies, Au-S
      bond lability did not appreciably impact the order of the assembly process.
      Temperature programming combines the selectivity of DNA-directed assembly with
      the ability to control the order in which several complementary strands hybridize
      in a common solution and could contribute to the synthesis of more complex
      nanostructured materials.

PMID- 16402781
TI  - Novel carbon-doped TiO2 nanotube arrays with high aspect ratios for efficient
      solar water splitting.
AB  - The photocatalytic splitting of water into hydrogen and oxygen using solar light
      is a potentially clean and renewable source for hydrogen fuel.(1,2) There has
      been extensive investigation into metal-oxide semiconductors such as TiO(2),
      WO(3), and Fe(2)O(3), which can be used as photoanodes in thin-film form.(3-5) Of
      the materials being developed for photoanodes, TiO(2) remains one of the most
      promising because of its low cost, chemical inertness, and photostability.(6)
      However, the widespread technological use of TiO(2) is hindered by its low
      utilization of solar energy in the visible region. In this study, we report the
      preparation of vertically grown carbon-doped TiO(2) (TiO(2-x)C(x)) nanotube
      arrays with high aspect ratios for maximizing the photocleavage of water under
      white-light irradiation. The synthesized TiO(2-x)C(x) nanotube arrays showed much
      higher photocurrent densities and more efficient water splitting under visible
      light illumination (> 420 nm) than pure TiO(2) nanotube arrays. The total
      photocurrent was more than 20 times higher than that with a P-25 nanoparticulate
      film under white-light illumination.

PMID- 16402782
TI  - Fabrication of biological nanostructures by scanning near-field photolithography
      of chloromethylphenylsiloxane monolayers.
AB  - We demonstrate the fabrication of sub-100-nm DNA surface patterns by scanning
      near-field optical lithography using a near-field scanning optical microscope
      coupled to a UV laser and a chloromethylphenylsiloxane (CMPS) self-assembled
      monolayer (SAM). The process involves 244-nm exposure of the CMPS SAM to create
      nanoscale patterns of surface carboxylic acid functional groups, followed by
      their conversion to the N-hydroxysuccinimidyl ester and reaction of the active
      ester with DNA to spatially control DNA grafting with high selectivity.

PMID- 16402783
TI  - Novel nanotube-on-insulator (NOI) approach toward single-walled carbon nanotube
      devices.
AB  - We present a novel nanotube-on-insulator (NOI) approach for producing high-yield
      nanotube devices based on aligned single-walled carbon nanotubes. First, we
      managed to grow aligned nanotube arrays with controlled density on crystalline,
      insulating sapphire substrates, which bear analogy to industry-adopted silicon-on
      insulator substrates. On the basis of the nanotube arrays, we demonstrated
      registration-free fabrication of both top-gated and polymer-electrolyte-gated
      field-effect transistors with minimized parasitic capacitance. In addition, we
      have developed a way to transfer these aligned nanotube arrays to flexible
      substrates successfully. Our approach has great potential for high-density, large
      scale integrated systems based on carbon nanotubes for both micro- and flexible
      electronics.

PMID- 16402784
TI  - Peptide-mediated formation of single-wall carbon nanotube composites.
AB  - The formation of silica- and titania-coated single-wall carbon nanotubes (SWNTs)
      using a mutlifunctional peptide to both suspend SWNTs and direct the
      precipitation of silica and titania at room temperature is demonstrated.

PMID- 16402785
TI  - Laser absorption scanning tunneling microscopy of carbon nanotubes.
AB  - We report single molecule laser absorption by carbon nanotubes stamped under
      ultrahigh vacuum onto Si(100)2x1:H surfaces. Absorption is detected by scanning
      tunneling microscopy. Images are obtained with and without modulated laser
      excitation using lock-in amplification and a rear-illumination geometry to reduce
      thermal effects. Noise appears at topographic edges and is analyzed by a
      quantitative model in terms of scan speed, mechanical instabilities, and feedback
      current fluctuations at the edge of the nanotubes. Noise due to mechanical
      instabilities is shown to persist even in the limit of slow scan speed.

PMID- 16402786
TI  - Ferromagnetic self-assembled quantum dots on semiconductor nanowires.
AB  - Ferromagnetic self-assembled alpha-MnAs quantum dots (QD) were grown epitaxially
      on metal catalyst-grown InAs nanowires (NW) by chemical vapor deposition.
      Magnetic force microscopy measurements demonstrated that the QDs are stable,
      single-domain ferromagnets with T(c) values of approximately 310 K. Single QD
      switching was demonstrated at fields as low as 60 Oe. The hybrid
      ferromagnetic/semiconductor QD/NW properties provide a promising basis for the
      development of nanowire spin-valves and magnetic memory devices.

PMID- 16402787
TI  - Controlled two-dimensional pattern of spontaneously aligned carbon nanotubes.
AB  - We report a simple solution process to form controlled patterns of aligned single
      walled carbon nanotubes on solid substrates. The essential step of the process is
      to deposit a dilute solution of DNA-wrapped carbon nanotubes (DNA-CNTs) on a
      SiO(2) surface covered with a thin hydrophobic layer. This leads to deposition of
      fully aligned CNTs. The alignment pattern can be controlled by metal electrodes
      in the deposition region and can be quantitatively modeled by the behavior of a
      quasi-two-dimensional DNA-CNT nematic phase near the solution/SiO(2) interface.
      These results point to the possibility of rational design and economical
      fabrication of CNT alignment patterns on solid substrates.

PMID- 16402788
TI  - Controlling the charge of a specific surface atom by the addition of a non-site
      specific single impurity in a Si nanocrystal.
AB  - We show, by use of self-consistent calculations, that the charge on a radical
      surface site (RSS) on a hydrogen-terminated silicon nanocrystal can be controlled
      by the addition of a non-site-specific dopant atom. An RSS is a surface defect
      where the H-termination is missing. This new effect has important implications
      for future hybrid semiconductor/molecular nanoelectronics. We also calculate the
      energy and wave function of the RSS state and its nanoscale interactions with the
      dopant atom.

PMID- 16402789
TI  - Autonomously moving nanorods at a viscous interface.
AB  - We study the autonomous motion of catalytic nanorods in Gibbs monolayers. The
      catalytic activity of the rods on a hydrogen peroxide aqueous subphase gives rise
      to anomalous translational and rotational diffusion. The rods perform a Levy-walk
      superdiffusive motion that can be decomposed into thermal orientation
      fluctuations and an active motion of the rods with a constant velocity along
      their long axis. Since interfacial dissipation increases relative to bulk phase
      dissipation when miniaturizing the size of objects moving in the interface, the
      autonomous nanorods allow for precise measurements of surface shear viscosities
      as low as a few nN s/m. The cross over from active motion toward passive
      diffusion when increasing the surfactant concentration is explained by a loss of
      friction asymmetry of the rods.

PMID- 16402790
TI  - Reciprocating power generation in a chemically driven synthetic muscle.
AB  - A scalable synthetic muscle has been constructed that transducts nanoscale
      molecular shape changes into macroscopic motion. The working material, which
      deforms affinely in response to a pH stimulus, is a self-assembled block
      copolymer comprising nanoscopic hydrophobic domains in a weak polyacid matrix. A
      device has been assembled where the muscle does work on a cantilever and the
      force generated has been measured. When coupled to a chemical oscillator this
      provides a free running chemical motor that generates a peak power of 20 mW kg(
      1) by the serial addition of 10 nm shape changes that scales over 5 orders of
      magnitude. It is the nanostructured nature of the gel that gives rise to the
      affine deformation and results in a robust working material for the construction
      of scalable muscle devices.

PMID- 16402791
TI  - Fundamental mechanism of translocation across liquidlike membranes: toward
      control over nanoparticle behavior.
AB  - We envision and theoretically investigate a novel behavior of a functionalized
      nanoparticle designed to translocate through a liquidlike membrane. We develop a
      statistical-mechanical approach to such a system. We predict a new mechanism for
      the opening of a circular energy-dominated pore on the membrane by a nanoparticle
      functionalized with a peptide aggregate. Following fluctuations in the position
      and orientation of the nanoparticle, the peptide aggregate incorporates into the
      membrane and locally destabilizes it. The nucleation of a pore centered at the
      peptide aggregate attached to the particle is a precursor to particle
      translocation. The subsequent opening of the pore is assisted by adhesion of the
      membrane to the particle. We determine the conditions in which thermal
      fluctuations in the membrane shape and the pore size can induce translocation of
      the particle. For different system parameters quantities such as the free energy,
      entropy, pore size, degree of particle wrapping, and the probability of
      spontaneous translocation are obtained.

PMID- 16402792
TI  - Multicolor FRET silica nanoparticles by single wavelength excitation.
AB  - Fluorescent nanoparticles with multiple emission signatures by a single
      wavelength excitation are needed in multiplex bioanalysis and molecular imaging.
      We have prepared silica nanoparticles encapsulated with three organic dyes using
      a modified Stober synthesis method. By varying the doping ratio of the three
      tandem dyes, fluorescence resonance energy transfer (FRET)-mediated emission
      signatures can be tuned to have the nanoparticles exhibit multiple colors under
      one single wavelength excitation. These nanoparticles are intensely fluorescent,
      highly photostable, uniform in size, and biocompatible. The acceptor emission of
      the FRET nanoparticles has generated a large Stokes shift, which implicates broad
      applications in biological labeling and imaging. Molecular recognition moieties,
      such as biotin, can be covalently attached to the nanoparticle surface to allow
      for specific binding to target molecules. These multicolor FRET silica
      nanoparticles can be used as barcoding tags for multiplexed signaling. By using
      these NPs, one can envision a dynamic, multicolor, colocalization methodology to
      follow proteins, nucleic acids, molecular machines, and assemblies within living
      systems.

PMID- 16402793
TI  - Salt dependence of ion transport and DNA translocation through solid-state
      nanopores.
AB  - We report experimental measurements of the salt dependence of ion transport and
      DNA translocation through solid-state nanopores. The ionic conductance shows a
      three-order-of-magnitude decrease with decreasing salt concentrations from 1 M to
      1 muM, strongly deviating from bulk linear behavior. The data are described by a
      model that accounts for a salt-dependent surface charge of the pore.
      Subsequently, we measure translocation of 16.5-mum-long dsDNA for 50 mM to 1 M
      salt concentrations. DNA translocation is shown to result in either a decrease
      ([KCl] > 0.4 M) or increase of the ionic current ([KCl] < 0.4 M). The data are
      described by a model where current decreases result from the partial blocking of
      the pore and current increases are attributed to motion of the counterions that
      screen the charge of the DNA backbone. We demonstrate that the two competing
      effects cancel at a KCl concentration of 370 +/- 40 mM.

PMID- 16402794
TI  - Thermal conductance of an individual single-wall carbon nanotube above room
      temperature.
AB  - The thermal properties of a suspended metallic single-wall carbon nanotube (SWNT)
      are extracted from its high-bias (I-V) electrical characteristics over the 300
      800 K temperature range, achieved by Joule self-heating. The thermal conductance
      is approximately 2.4 nW/K, and the thermal conductivity is nearly 3500 Wm(-1)K(
      1) at room temperature for a SWNT of length 2.6 mum and diameter 1.7 nm. A subtle
      decrease in thermal conductivity steeper than 1/T is observed at the upper end of
      the temperature range, which is attributed to second-order three-phonon
      scattering between two acoustic modes and one optical mode. We discuss sources of
      uncertainty and propose a simple analytical model for the SWNT thermal
      conductivity including length and temperature dependence.

PMID- 16402795
TI  - DNA nanomechanical switches under folding kinetics control.
AB  - Existing DNA nanodevices operate at equilibrium under changes in solution
      composition. We propose an alternative DNA switch design that can be driven and
      maintained out of equlibrium, under fixed chemical conditions. Moderate cooling
      rate after heat denaturation drives the switch to its lowest energy conformation,
      while rapid cooling (>100 degrees C/ms) locks the molecule in a unique
      alternative conformation that is retained over weeks at room temperature. This
      reversible process is probed using fluorescent energy transfer. DNA switches
      operating out of equilibrium should be more amenable to nanotechnology
      applications and scalable integration.

PMID- 16402796
TI  - Fabrication and characterization of nanopore-based electrodes with radii down to
      2 nm.
AB  - We report on the fabrication and characterization of gold nanoelectrodes with
      carefully controlled nanometer dimensions in a matrix of insulating silicon
      nitride. A focused electron beam was employed to drill nanopores in a thin
      silicon nitride membrane. The size and shape of the nanopores were studied with
      high-resolution transmission electron microscopy and electron-energy-loss two
      dimensional maps. The pores were subsequently filled with gold, yielding
      conically shaped nanoelectrodes. The nanoelectrodes were examined by atomic and
      electrostatic force microscopy. Their applicability in electrochemistry was
      demonstrated by steady-state cyclic voltammetry. Pores with a radii down to 0.4
      nm and electrodes with radii down to 2 nm are demonstrated.

PMID- 16402798
TI  - Photoinduced direct electron transfer from InSe to GaSe semiconductor
      nanoparticles.
AB  - Direct electron transfer from InSe nanoparticles to GaSe nanoparticles in mixed
      solution-phase aggregates has been found to occur upon photoexcitation. Mixed
      aggregates exhibit a strong charge-transfer absorption band at an energy slightly
      higher than the InSe band gap. Photoexcitation of this band results in a
      polarized transient absorption spectrum and transient absorption kinetics
      characteristic of InSe valence-band holes and GaSe conduction-band electrons. The
      kinetics indicate that charge separation persists for at least several hundred
      picoseconds.

PMID- 16402797
TI  - Nanoparticle-mediated local and remote manipulation of protein aggregation.
AB  - The local heat delivered by metallic nanoparticles selectively attached to their
      target can be used as a molecular surgery to safely remove toxic and clogging
      aggregates. We apply this principle to protein aggregates, in particular to the
      amyloid beta protein (Abeta) involved in Alzheimer's disease (AD), a
      neurodegenerative disease where unnaturally folded Abeta proteins self-assemble
      and deposit forming amyloid fibrils and plaques. We show the possibility to
      remotely redissolve these deposits and to interfere with their growth, using the
      local heat dissipated by gold nanoparticles (AuNP) selectively attached to the
      aggregates and irradiated with low gigahertz electromagnetic fields. Simultaneous
      tagging and manipulation by AuNP of Abeta at different stages of aggregation
      allow both, noninvasive exploration and dissolution of molecular aggregates.

PMID- 16402799
TI  - From ballistic transport to tunneling in electromigrated ferromagnetic
      breakjunctions.
AB  - We fabricate ferromagnetic nanowires with constrictions whose cross section can
      be reduced gradually from 100 x 30 nm(2) to the atomic scale and eventually to
      the tunneling regime by means of electromigration. The contacts are mechanically
      and thermally stable. We measure low-temperature magnetoresistances (MR) < 3% for
      contacts < 400 Omega, reproducible MR variations that are nonmonotonic in the
      regime 400 Omega - 25 kOmega, and a maximum MR of 80% for atomic-scale widths.
      These results for devices > 400 Omega differ from previous room-temperature
      studies of electrodeposited devices. For samples in the tunneling regime, we
      observe large fluctuations in MR, between -10 and 85%.

PMID- 16402800
TI  - Localization/Quasi-delocalization transitions and quasi-mobility-edges in shell
      doped nanowires.
AB  - We propose a novel concept, namely, shell-doping of nanowires, for control of
      carrier mobility in nanowires. Different from traditional doping, where dopant
      atoms are distributed uniformly inside nanowires, shell-doping spatially confines
      dopant atoms within a few atomic layers in the shell region of a nanowire. Our
      numerical results based on the Anderson model of electronic disorder show that
      electrons in a shell-doped nanowire exhibit a peculiar behavior very different
      from that of uniformly doped nanowires. Beyond some critical doping, electron
      dynamics in a shell-doped nanowire undergoes a localization/quasi-delocalization
      transition, namely, the electron diffusion length decreases in the regime of weak
      disorder but increases in the regime of strong disorder. This transition is a
      result of the existence of quasi-mobility-edges in the energy spectrum of the
      system, which can be exploited experimentally through control of electron
      concentration, carrier density, and degree of disorder.

PMID- 16402801
TI  - Simulation of grafted polymers on nanopatterned surfaces.
AB  - Structural properties of polymer brushes on nanopatterned surfaces in good
      solvent have been determined by computer simulations. Scaling relations for the
      brush height and brush width are proposed. The properties of the central part of
      the patterned brush remain constant as long as the pattern is wider than a few
      times the brush height. The results agree qualitatively with recent AFM
      experiments, but some quantitative differences call for a reassessment of
      experimental procedures.

PMID- 16402802
TI  - Localized deposition of coronene molecules on Si(001)-2x1 using a scanning
      tunneling microscope tip source.
AB  - The deposition of coronene molecules from scanning tunneling microscope (STM)
      tips onto a clean Si(001)-2x1 surface at 25 degrees C was investigated. The STM
      tips, contaminated with coronene, were found to deposit coronene molecules on the
      clean Si(001) surface, allowing patterns to be generated. Covalent Si-C chemical
      bonds, formed between the coronene molecules and the Si substrate, froze the flip
      flop motion of the adjacent Si-Si dimers on the substrate. In most cases, the
      mode of coronene bonding to Si(001) is independent of whether deposition occurs
      from the gas phase or from the STM tip. Despite the covalent chemical bonds
      formed between the coronene molecule and the Si substrate, the STM tip can drag
      the coronene laterally on the Si substrate without inducing a chemical change in
      the molecule. Sharp spikes observed in the tunneling current during the coronene
      deposition reflect the abrupt decrease of the tip-substrate distance at the
      instant of transport of the molecule from tip to surface.

PMID- 16402804
TI  - Structure, stability, and hydration of a polypeptide in AOT reverse micelles.
AB  - In this communication, we provide theoretical evidence that the folded structure
      of a simple peptide, alanine zwitterionic octapeptide, or A8, unstable in
      solution, becomes stable in a reverse micelle (RM) of appropriate size. Our
      molecular dynamics simulations were carried out for realistic models of sodium 2
      ethylhexylsulfosuccinate RM in isooctane, simulated for an extended period of
      time. For the RM of the smaller size, we find that a helical structure is stable
      for the whole length of the simulation. On the contrary, the peptide very quickly
      takes an extended structure in larger micelles.

PMID- 16402805
TI  - Palladium-catalyzed [3 + 2] intramolecular cycloaddition of alk-5
      enylidenecyclopropanes.
AB  - Readily accessible alk-5-enylidenecyclopropanes undergo [3 + 2] intramolecular
      cycloaddition reactions upon treatment with appropriate palladium complexes. The
      method allows the rapid and efficient assembly of a variety of
      bicyclo[3.3.0]octane systems with up to three stereocenters. Preliminary
      theoretical calculations uncovered previously unsuspected mechanistic
      possibilities based on either a concerted pallada-ene-like rearrangement or a
      stepwise process involving zwitterionic intermediates.

PMID- 16402806
TI  - Synthesis of an artificial cell surface receptor that enables oligohistidine
      affinity tags to function as metal-dependent cell-penetrating peptides.
AB  - Cell-penetrating peptides and proteins (CPPs) are important tools for the
      delivery of impermeable molecules into living mammalian cells. To enable these
      cells to internalize proteins fused to common oligohistidine affinity tags, we
      synthesized an artificial cell surface receptor comprising an N-alkyl derivative
      of 3beta-cholesterylamine linked to the metal chelator nitrilotriacetic acid
      (NTA). This synthetic receptor inserts into cellular plasma membranes, projects
      NTA headgroups from the cell surface, and rapidly cycles between the plasma
      membrane and intracellular endosomes. Jurkat lymphocytes treated with the
      synthetic receptor (10 microM) for 1 h displayed approximately 8,400,000
      [corrected]NTA groups on the cell surface. Subsequent addition of the green
      fluorescent protein AcGFP fused to hexahistidine or decahistidine peptides (3
      microM) and Ni(OAc)(2) (100 microM) enhanced the endocytosis of AcGFP by 150-fold
      (hexahistidine fusion protein) or 600-fold (decahistidine fusion protein) within
      4 h at 37 degrees C. No adverse effects on cellular proliferation or morphology
      were observed under these conditions. By enabling common oligohistidine affinity
      tags to function as cell-penetrating peptides, this metal-chelating cell surface
      receptor provides a useful tool for studies of cellular biology [corrected]

PMID- 16402808
TI  - Biomolecular embossing.
AB  - The replica molding and embossing of DNA texture has been achieved using a
      conventional polyurethane mold. The final process requires no additional or
      separate extraction phases. The polyurethane replica is stable up to 150 degrees
      C and possesses a good longevity and a capacity to emboss a biological entity
      into a thermosetting plastic such as poly(ethylene terephthalate).

PMID- 16402807
TI  - The incorporation of a photoisomerizable amino acid into proteins in E. coli.
AB  - An orthogonal aminoacyl tRNA synthetase/tRNA pair has been evolved that allows
      the incorporation of the photoisomerizable amino acid phenylalanine-4'-azobenzene
      (AzoPhe) into proteins in E. coli in response to the amber nonsense codon.
      Further, we show that AzoPhe can be used to photoregulate the binding affinity of
      catabolite activator protein to its promoter. The ability to selectively
      incorporate AzoPhe into proteins at defined sites should make it possible to
      regulate a variety of biological processes with light, including enzyme,
      receptor, and ion channel activity.

PMID- 16402809
TI  - A mild etch for the fabrication of three-dimensional nanostructures in gold.
AB  - A novel mild etch is reported for the fabrication of three-dimensional structures
      in gold films when used in conjunction with an alkylthiol resist. This etch
      consists of a solution of mercaptoethylamine in ethanol to which a small amount
      of ammonium hydroxide has been added. Using mask-based photolithography, micron
      scale features have been created that exhibit good edge definition. For long
      chain thiols, there is little tendency for the regions protected by thiols to be
      eroded on extended exposure to the etch solution. In conjunction with scanning
      near-field photolithography, the new etch solution enables the fabrication of
      nanoscale structures with dimensions significantly smaller than the conventional
      diffraction limit.

PMID- 16402810
TI  - Kinetic isotope effect is a sensitive probe of spin state reactivity in C-H
      hydroxylation of N,N-dimethylaniline by cytochrome P450.
AB  - This paper presents DFT calculations of C-H hydroxylation of N,N-dimethylaniline
      by Compound I (Cpd I) of cytochrome P450. The reaction involves two processes
      nascent from the two spin states of Cpd I, the low-spin (LS) and high-spin (HS)
      states. The calculations demonstrate that the kinetic isotope effects (KIEs) of
      the two processes are very different, and only KIELS fits the experimental datum.
      As such, KIE can be a sensitive probe of spin state reactivity.

PMID- 16402812
TI  - A ratiometric fluorescent viscosity sensor.
AB  - The development of a dual probe that provides ratiometric measurements of fluid
      viscosity is described. The design is based on coupling of a primary fluorophore
      with viscosity-independent fluorescence emission (blue unit) with a secondary
      fluorophore that exhibits viscosity-sensitive fluorescent emission quantum yield
      (red unit). Excitation of the secondary fluorophore can be achieved via Resonance
      Energy Transfer. The ratio of the fluorescence emission of these fluorophores
      provides an accurate, ratiometric measurement of solvent viscosity.

PMID- 16402811
TI  - Enhanced base pairing and replication efficiency of thiothymidines, expanded-size
      variants of thymidine.
AB  - Here we test the steric effects of added size on DNA base pairing and replication
      by the use of thiocarbonyl group replacements for natural nucleoside thymidine.
      The 2-thioT (2S) and 4-thioT (4S) nucleosides were reported previously, but their
      pairing specificity and replication fidelity were unknown. We find that 2S pairs
      with higher specificity than thymidine, and both 2S and 4S nucleoside
      triphosphates are replicated with higher efficiency than natural dTTP. The
      results indicate possible biotechnological uses for these analogues and have
      implications in the ongoing use of thionucleobases in cancer treatment.

PMID- 16402813
TI  - A luminescent silver-adenine metallamacrocyclic quartet.
AB  - This communication describes formation of a 3N-coordinated silver-modified
      adenine metallamacrocyclic quartet in solid state, its aggregative ordering on
      graphite surface, and luminescence.

PMID- 16402814
TI  - Zinc(II)- and copper(I)-mediated large two-photon absorption cross sections in a
      bis-cinnamaldiminato Schiff base.
AB  - A Schiff base ligand has been synthesized by condensing 1,2-diaminobenzene with 4
      (dimethylamino)cinnamaldehyde to give a donor-pi-acceptor-pi-donor system which
      does not show any two-photon absorption cross section but which does, upon
      complexation with Zn(II) or Cu(I), exhibit very high two-photon absorption cross
      sections.

PMID- 16402815
TI  - Direct observation of enhanced translocation of a homeodomain between DNA cognate
      sites by NMR exchange spectroscopy.
AB  - A novel approach is presented for studying the kinetics of specific protein-DNA
      interactions by NMR exchange spectroscopy. The experimental design involves the
      direct observation of translocation of a homeodomain between cognate sites on two
      oligonucleotide duplexes, differing by only a single base pair at the edge of the
      DNA recognition sequence. The single base-pair change perturbs the 1H-15N
      correlation spectrum of a number of residues, while leaving the affinity for the
      DNA unchanged. The exchange process has apparent rate constants in the 5-20 s-1
      range which are linearly dependent upon the concentration of free DNA. These
      rates are about 3 orders of magnitude larger than the dissociation rate constant
      determined by gel shift assays at nanomolar DNA concentrations. The complete NMR
      exchange data set, comprising auto- and cross-peak intensities as a function of
      mixing time at five concentrations of free DNA, can be fit simultaneously to a
      simple model in which protein translocation between DNA duplexes occurs via a
      second-order process (with rate constants of approximately 6 x 104 M-1 s-1)
      involving direct collision of a protein-DNA complex with free DNA. This is akin
      to intersegmental transfer, and a physical model for the process is discussed.
      Rapid translocation at high concentrations of free DNA observed directly by NMR
      exchange spectroscopy reconciles the long half-lives of protein-DNA complexes
      measured by biochemical analysis in vitro with the highly dynamic behavior of
      such complexes observed in vivo. The relevance of this mechanism to the kinetics
      of protein-DNA interactions within the cell is discussed.

PMID- 16402816
TI  - Self-trapping of spatially and temporally incoherent white light in a
      photochemical medium.
AB  - We report that a beam of spatially and temporally incoherent white light self
      traps by initiating free-radical polymerization in an organosiloxane medium.
      Refractive index changes due to polymerization lead to the formation of a narrow
      channel waveguide that traps and guides the entire multimode, broadband beam
      without diffraction. The response time of the system, which is determined by the
      inherently slow rate of free-radical polymerization, exceeds by several orders of
      magnitude the femtosecond-scale random phase fluctuations that characterize white
      light. Self-trapping of incoherent light is possible in the photochemical medium
      because it responds to the time-averaged intensity profile of the white light
      beam.

PMID- 16402817
TI  - Titanium(II)-mediated cyclizations of (silyloxy)enynes: a total synthesis of (-)
      7-demethylpiericidin A1.
AB  - A concise total synthesis of 7-demethylpiericidin A1 has been completed. The
      synthesis features a titanium(II)-mediated cyclization of a (silyloxy)enyne as
      the key step and proceeds in nine steps from tiglic aldehyde.

PMID- 16402818
TI  - Targeted cleavage of HIV rev response element RNA by metallopeptide complexes.
AB  - Stoichiometric targeting and site-specific cleavage of HIV RRE RNA is
      demonstrated under physiologically relevant conditions by use of a metallopeptide
      that combines a specific RNA recognition sequence with a metal binding domain.
      Mass spectrometric analysis of cleavage products following treatment of target
      RNA with the metallopeptide, ascorbate, and dioxygen are consistent with C-1'H or
      C-4'H oxidative cleavage paths with an apparent second-order rate constant k2
      approximately 700 M-1 min-1.

PMID- 16402819
TI  - Accelerated electrocyclic ring-opening of benzocyclobutenes under the influence
      of a beta-silicon atom.
AB  - A significant acceleration effect of a beta-silicon atom was observed on the
      electrocyclic ring-opening reaction of benzocyclobutene derivatives to form o
      quinodimethanes. This acceleration effect could be attributed to an electronic
      sigma-donating nature of the C(alpha)-Si(beta) bond, associated with alpha-anion
      driven pericyclic reactions.

PMID- 16402820
TI  - Direct measure of the hydration number of aqueous methane.
AB  - A hydration number of 20 has been measured for aqueous CH4 in the temperature
      range 273-298 K on the basis of the simultaneous observation of the 13C isotropic
      resonance lines of CH4 in both aqueous solution and the dodecahedral cage of CH4
      structure I hydrate. Additional experimental evidence and analysis reported in
      this paper suggest that the dominant aqueous hydration number of methane is 20.

PMID- 16402821
TI  - Direct observation of reactive trapped holes in TiO2 undergoing photocatalytic
      oxidation of adsorbed alcohols: evaluation of the reaction rates and yields.
AB  - To investigate the primary process of photocatalytic oxidation of TiO2,
      interfacial charge-transfer reaction of trapped holes formed in nanocrystalline
      TiO2 films by UV irradiation was directly measured by highly sensitive
      femtosecond and nanosecond transient absorption spectroscopy under low intensity
      excitation condition to avoid fast electron-hole recombination. Accordingly, the
      rates and yields of photocatalytic oxidation of several alcohols adsorbed on TiO2
      were evaluated successfully.

PMID- 16402823
TI  - Facile synthesis of tin oxide nanoparticles stabilized by dendritic polymers.
AB  - Tin(IV) oxide nanoparticles were synthesized via the reaction of carbon dioxide
      with stannate ions immobilized by dendritic polymers. For PAMAM and PPI dendrimer
      hosts, resultant nanoparticle diameters were 2.5-3 nm; 3-3.5 nm nanoparticles
      resulted from use of a poly(ethyleneimine) hyperbranched polymer. Our conditions
      represent the only precedent for SnO2 nanoparticulate growth using dendritic
      architectures, as well as a novel application for CO2 as a reactive gas for the
      controlled growth of metal oxide nanoparticles.

PMID- 16402822
TI  - Selective labeling of extracellular proteins containing polyhistidine sequences
      by a fluorescein-nitrilotriacetic acid conjugate.
AB  - The compound NTA-DCF consists of two components, a dichlorofluorescein (DCF)
      reporter and a nitrilotriacetic acid (NTA) functionality. The latter binds
      polyhistidine sequences selectively through a bridging metal ion. The NTA-DCF
      conjugate has photophysical properties similar to those of the parent DCF
      fluorophore both by itself and as its nickel(II) complex. The insensitivity of
      the emission to paramagnetic ions allows the probe to label His6-tagged proteins
      fluorescently on the extracellular surfaces of HEK 293-T and HeLa cells.

PMID- 16402824
TI  - A stable silaborene: synthesis and characterization.
AB  - A stable silicon-boron doubly bonded compound, silaborene (2), was synthesized by
      the reaction of 1,1-dilithiosilane (1) with dichloro(2,2,6,6
      tetramethylpiperidino)borane in toluene. The X-ray crystallographic analysis of 2
      revealed that the >Si=B-N< framework is almost linear (176.87(13) degrees ) with
      an Si-B bond length of 1.8379(17) A, which is about 10% shorter than typical Si-B
      single bonds. The silaborene 2 reacted with lithium trimethylsilylacetylide at 60
      degrees C in DME to give the corresponding silaborenide (4-.[Li(dme)3]+), whose
      reddish-orange crystals were isolated as the solvent separated ion pair. The X
      ray analysis of 4-.[Li(dme)3]+ showed that the Si-B bond length (1.933(3) A) is
      longer than that of 2, but still shorter than typical Si-B single bonds. These
      structural features indicate that 4- has double bond character involving the
      >Si=B<- resonance structure.

PMID- 16402825
TI  - A planar water tetramer with tetrahedrally coordinated water embedded in a
      hydrogen bonding network of [Tc4(CO)12-(mu3-OH)4.4H2O].
AB  - A virtually planar water tetramer in which the water molecules are virtually
      tetrahedrally coordinated could be realized in the solid in a three-dimensional
      network of [Tc4(CO)12-(mu3-OH)4.4H2O]. The network could be produced by
      cocrystallization of the new cubane-like cluster [Tc(CO)3-(mu3-OH)]4 and water as
      a complementary component. The amphiphilic behavior of cluster and water results
      in a highly ordered three-dimensional network. The complementary components, the
      water tetramer and the cubic cluster, independently of one another form two
      interpenetrating tetragonal lattice networks held together exclusively by
      hydrogen bonds.

PMID- 16402826
TI  - Total synthesis of UCS1025A.
AB  - The enantioselective total synthesis of the telomerase inhibitor UCS1025A has
      been accomplished. The key transformation involves a remarkable boron Reformatsky
      coupling of iodolactone 13 and aldehyde 17.

PMID- 16402827
TI  - Hydrogen-substituted osmium silylene complexes: effect of charge localization on
      catalytic hydrosilation.
AB  - Addition of bulky primary silanes to the osmium benzyl compound,
      Cp*(iPr3P)OsCH2Ph, afforded two neutral hydrogen-substituted silylene complexes
      via activation of two Si-H bonds. These species have been structurally
      characterized, and their reactivity has been examined experimentally and
      computationally. Comparison of these neutral silylene complexes with their
      cationic analogue highlights the dramatic influence of charge distribution on the
      reaction chemistry of metal silylene complexes.

PMID- 16402828
TI  - Self-assembled nanodisks with targetlike multirings aggregated at the air-water
      interface.
AB  - In this communication, we report the self-assembly of zirconia by mixing its
      precursor with another solution containing surfactant as well as gelatin. The
      resulting zirconia product consists of many disks with a range of diameter from
      approximately 100 nm to approximately 2 mum. These disks can be assembled inside
      aqueous systems. Meanwhile the disks rise gradually and eventually form a visible
      film at the air-water interface. Remarkably, the structure of zirconia disks
      templated by surfactant has been found to be targetlike multirings with a d
      spacing of approximately 3.3 nm. We propose that a successful multirings self
      assembly depends on two different template-functions from the same surfactant,
      excellent tenacity of the zirconia layers and the strong ability of the gelatin
      to stabilize and disperse the disks.

PMID- 16402830
TI  - Changes in coordination of sterically demanding hybrid imidazolylphosphine
      ligands on Pd(0) and Pd(II).
AB  - Low-coordinate organometallic complexes are important in structure and catalysis,
      and hemilability or secondary interactions such as hydrogen bonding enabled by
      hybrid ligands are receiving increasing attention. To study the factors
      controlling these phenomena, three new imidazol-2-ylphosphine ligands, L, were
      made. In these ligands, the bulk around P and the hindrance at the basic and
      potentially coordinating imidazole N-3 were varied. Remarkably, L(2)Pd(0)
      complexes 3a-c were shown to be two-coordinate, 12-electron species, despite the
      availability of imidazole N-3 to enter into eta(2)-P,N chelation. In oxidative
      additions of C-X bonds to the Pd(0) complexes, reaction rates and products could
      be controlled by the nature of the C and X groups and the R groups on the
      phosphine. Most significantly, whereas 4c-PhI and 4c-MeOTf from 3c are normal
      trans-bis(phosphine)Pd(R)(X) species, 5a-PhI, 5a-PhBr, and 5b-PhI from 3a and 3b
      were shown by X-ray diffraction to be a monomeric species with a single eta(2)
      P,N-chelating phosphine. From 3a and methyl triflate, an ionic complex [6a
      Me](+)[OTf](-) with one chelating and one nonchelating phosphine was formed, with
      temperature-dependent windshield-wiper exchange of the two, showing hemilability.
      Thus, large phosphine substituents (R = tert-butyl rather than isopropyl) favor
      chelation. The chelate Pd-imidazole N-3 bond is longer when the heterocyclic
      nitrogen is hindered by an adjacent tert-butyl group at C-4 (comparing 5a-PhI and
      5b-PhI). Finally, whereas in [8b-Ph](+)[OTf](-) from 5b-PhI and isopropylamine,
      the amine coordinates without chelate opening or hydrogen bonding, in [10c
      Me](+)[OTf](-) made from 4c-MeOTf and isopropylamine, the amine is not only
      coordinated at N but also donates a hydrogen bond to each phosphine imidazol-2-yl
      substituent.

PMID- 16402829
TI  - Polyhydroxylated sapphyrins: multisite non-metallic catalysts for activated
      phosphodiester hydrolysis.
AB  - Enhanced hydrolysis rates for the cleavage of bis(4-nitrophenyl)phosphate (BNPP),
      a model phosphodiester, may be achieved by using appropriately designed ditopic
      receptors containing the known phosphate-binding nucleus, sapphyrin, attached
      covalently to suitably oriented polyhydroxyl subunits. Evidence for the
      interaction between sapphyrin and BNPP comes from solid-state X-ray diffraction
      analysis of a diprotonated dihydroxylated sapphyrin-BNPP complex and from
      solution-phase (31)P NMR spectroscopic binding studies. The sapphyrins described
      in this paper may have a role to play as oligonucleotide cleavage agents.

PMID- 16402831
TI  - Steric control of bacteriochlorophyll ligation.
AB  - The axial coordination of central Mg(2+) ion in chlorophylls is of great
      structural and functional importance for virtually all photosynthetic chlorophyll
      proteins; however, little thermodynamic data are available on the ligand binding
      to these pigments. In the present study, spectral deconvolution of the
      bacteriochlorophyll Q(X) band serves to determine the ligand binding equilibria
      and relationships between thermodynamic parameters of ligand binding, ligand
      properties, and steric interactions occurring within the pigment. On the basis of
      the temperature effects on coordination, DeltaH degrees, DeltaS degrees, and
      DeltaG degrees of binding various types of ligands (acetone, dimethylformamide,
      imidazole, and pyridine) to diastereoisomeric bacteriochlorophylls were derived
      from respective van't Hoff's plots. At ambient temperatures, only ligation by
      imidazole and pyridine occurs spontaneously while DeltaG degrees becomes positive
      for ligation by acetone and dimethylformamide, due to a relatively large entropic
      effect, which is dominating when the energetic effects of ligation are small. It
      reflects, in quantitative terms, the control of the equatorial coordination of
      the Mg(2+) ion via the axial coordination: a "hard" free Mg(2+) ion is made into
      a softer center through the coordination of tetrapyrrole. Pigment structural
      features have comparable effects on the energetic and entropic contributions to
      the difference of ligation free energy between the diastereoisomers of
      bacteriochlorophyll. DeltaS degrees and DeltaH degrees values are consistently
      lower for the S epimer, most likely due to the steric crowding between bulky
      substituents. The two epimers show a 5 J.mol(-1).K(-1) difference in DeltaS
      degrees values, regardless of the ligand type, while the difference in DeltaH
      degrees amounts to 1.7 kJ.mol(-1), depending on the ligand. Such steric control
      of ligation would relate to the partial diastereoselectivity of chlorophyll self
      assembly and, in particular, the very high diastereoselectivity of the ligation
      of chlorophylls in photosynthetic proteins.

PMID- 16402832
TI  - Synthesis of transient and stable C-amino phosphorus ylides and their
      fragmentation into transient and stable carbenes.
AB  - Only basic phosphines, such as tris(dimethylamino)phosphine, allow for the
      synthesis of a stable acyclic beta-amino phosphonium salt 1c, which upon
      deprotonation with butyllithium affords the corresponding stable C-amino
      phosphorus ylide 2c. In contrast, cyclic beta-amino phosphonium salts 5a and 5b
      are stable despite the presence of weakly basic triarylphosphine fragments. They
      are prepared by intramolecular insertion of the carbene center of
      (amino)(phosphonio)carbenes into the CH bond of a phosphorus substituent.
      Deprotonation of 5a leads to the corresponding cyclic C-amino phosphorus ylide
      6a, which has been fully characterized including an X-ray diffraction study.
      Deprotonation of 5b affords enamine 8, probably via fragmentation of ylide 6b
      into transient carbene 7b and a subsequent 1,2-hydrogen shift. Transient cyclic C
      amino phosphorus ylides 6c and 6d have been prepared by intramolecular addition
      of a carbanion generated by deprotonation of a phosphorus substituent. Three
      membered heterocycle 6c rearranges into alkene 9, whereas the four-membered ring
      system undergoes a ring opening affording the stable carbene 7d. The latter
      results pave the route for the synthesis of various mixed carbene-phosphine
      bidentate ligands.

PMID- 16402833
TI  - Organometallic enantiomeric scaffolding: organometallic chirons. Total synthesis
      of (-)-Bao Gong Teng A by a molybdenum-mediated [5 + 2] cycloaddition.
AB  - Bao Gong Teng A, an optically active tropane alkaloid with hypotensive and miotic
      activity isolated from the Chinese herb Erycibe obtusifolia Benth, was
      synthesized by an "organometallic chiron" strategy in which single enantiomers of
      TpMo(CO)(2)(eta(3)-pyridinyl) complexes are produced in quantity and then
      elaborated easily and efficiently to generate, after demetalation, highly
      enantiopure advanced synthetic intermediates possessing the tropane core.

PMID- 16402834
TI  - Gauging the relative oxidative powers of compound I, ferric-hydroperoxide, and
      the ferric-hydrogen peroxide species of cytochrome P450 toward C-H hydroxylation
      of a radical clock substrate.
AB  - Density functional calculations were performed in response to the controversies
      regarding the identity of the oxidant species in cytochrome P450. The
      calculations were used to gauge the relative C-H hydroxylation reactivity of
      three potential oxidant species of the enzyme, the high-valent oxo-iron species
      Compound I (Cpd I), the ferric hydroperoxide Compound 0 (Cpd 0), and the ferric
      hydrogen peroxide complex Fe(H(2)O(2)). The results for the hydroxylation of a
      radical probe substrate, 1, show the following trends: (a) Cpd I is the most
      reactive species; in its presence the other two reagents will be silent. (b) In
      the absence of Cpd I, substrate oxidation by Cpd 0 and Fe(H(2)O(2)) will take
      place via a stepwise mechanism that involves initial O-O homolysis followed by H
      abstraction from 1. (c) Cpd 0 will undergo mostly porphyrin hydroxylation and
      only approximately 15% of substrate oxidation producing mostly the rearranged
      alcohol, 3 (Scheme 2). (d) Fe(H(2)O(2)) will generate mostly free hydrogen
      peroxide (uncoupling). A small fraction will perform substrate oxidation and lead
      mostly to 3. Reactivity probes for these reagents are kinetic isotope effect
      (KIE) and the product ratio of unrearranged to rearranged alcohols, [2/3]. Thus,
      for substrate oxidation by Cpd 0 or Fe(H(2)O(2)) KIE will be small, approximately
      2, while Cpd I will have large KIE values. Typically both Cpd 0 and Fe(H(2)O(2))
      will lead to a [2/3] ratio < 1, while Cpd I will lead to ratios > 1. In addition,
      the product isotope effect (KIE(2)/KIE(3) not equal 1) is expected from the
      reactivity of Cpd I.

PMID- 16402836
TI  - Specific ion pairing and interfacial hydration as controlling factors in gemini
      micelle morphology. Chemical trapping studies.
AB  - Results from chemical trapping experiments in micellar solutions containing 1.5-5
      mM aqueous solutions of three didodecyl dicationic dibromide gemini surfactants
      with different methylene spacer lengths (12-n-12 2Br where n = 2-4 CH(2) groups)
      gave quantitative estimates of the molarities of interfacial bromide (Br(m)) and
      water (H(2)O(m)), the fractions of free and paired headgroups and counterions,
      and the net headgroup charge. These results are one of the most detailed
      compositional studies of an association colloid interface to date. Br(m)
      increases and H(2)O(m) decreases as n decreases and the two cationic charges are
      closer together. The 12-2-12 2Br gemini (the only one of the three geminis known
      to form threadlike micelles) shows a marked increase in Br(m) (from 2.3 to 3.6 M)
      and a decrease in H(2)O(m) (from 35 to 17 M) at the exceptionally low surfactant
      concentration in the vicinity of the previously reported sphere-to-rod transition
      or second cmc concentration. Rod formation occurs because of an increase in
      headgroup-counterion association and dehydration at the micelle surface that
      depend on both the free energies of hydration and specific ion interactions and
      surfactant and counterion concentrations. These and other recent chemical
      trapping results support a new model for the balance of forces controlling
      morphological transitions of association colloids. The hydrophobic effect drives
      the formation of headgroup-counterion pairs, which have a lower demand for water
      of hydration. Release of water permits tighter packing and formation of
      cylindrical aggregates.

PMID- 16402835
TI  - Oxygen independent DNA interstrand cross-link formation by a nucleotide radical.
AB  - A 5-(2'-Deoxyuridinyl)methyl radical (1) was independently generated from three
      photochemical precursors and is the first example of a DNA radical that forms
      interstrand cross-links. Oxygen labeling experiments support generation of 1 by
      all precursors. Interstrand cross-links are produced upon irradiation of DNA
      containing any of the precursors. Cross-linking occurs via reaction with the
      opposing 2'-deoxyadenosine and is independent of O(2). The independence of cross
      link formation on O(2) is explained by kinetic analysis, which shows that the
      radical reacts reversibly with O(2). Examination of the effects of glutathione on
      cross-link formation under anaerobic conditions suggests that adoption of the syn
      conformation by 1 is the rate-limiting step in the process. Interstrand cross
      link formation is reversible in the presence of a good nucleophile. The stability
      of the interstrand cross-link suggests that the isolated molecule is a
      rearrangement product of that formed in solution. The rearrangement is a
      consequence of the isolation procedure but also occurs slowly in solution. Oxygen
      independent cross-link formation may be useful for the purposeful damage of DNA
      in hypoxic tumor cells, where O(2) is deficient.

PMID- 16402837
TI  - NO-releasing zeolites and their antithrombotic properties.
AB  - Transition metal-exchanged zeolite-A adsorbs and stores nitric oxide in
      relatively high capacity (up to 1 mmol of NO/g of zeolite). The stored NO is
      released on contact with an aqueous environment under biologically relevant
      conditions of temperature and pH. The release of the NO can be tuned by altering
      the chemical composition of the zeolite, by controlling the amount of water
      contacting the zeolite, and by blending the zeolite with different polymers. The
      high capacity of zeolite for NO makes it extremely attractive for use in
      biological and medical applications, and our experiments indicate that the NO
      released from Co-exchanged zeolite-A inhibits platelet aggregation and adhesion
      of human platelets in vitro.

PMID- 16402838
TI  - Super-helix formation induced by cyanine J-aggregates onto random-coil
      carboxymethyl amylose as template.
AB  - The J-aggregation of Cyanine-1dye in the presence of carboxymethyl amylose (CMA)
      is described. The J-aggregation requires a large excess CMA concentration; the J
      band maximum appears in the concentration range, [CMA]/[dye] = 10-50, depending
      on the degree of substitution (DS) of carboxylation, where [CMA] is the
      concentration of polymer repeat units. An extraordinarily large induced circular
      dichroism (CD) is observed from J-aggregates of the achiral cyanine dye in
      association with a random coil CMA, suggesting that the CMA is transformed into a
      helix. The magnitude of CD intensity increases with increasing DS of CMA and pH
      up to neutral (where a maximum J-aggregation occurs), while the CMA-bound dye
      monomer and H-aggregates (occurring at pH > or = 9) exhibit no induced CD. The
      trend in the CD intensity (of the J-aggregates) is in parallel with the
      fluorescence intensity of the J-aggregates. This suggests that binding of the J
      aggregates onto the template CMA is sterically controlled by the asymmetric
      environment of glucose residues (of CMA) so that more twisting power is exerted
      with increasing DS (of CMA), rendering the cyanine dye/CMA complex a more rigid
      (a high fluorescence intensity) super-helix. This is also revealed by the AFM
      image of a long strand.

PMID- 16402839
TI  - Infrared spectroscopy of phenylalanine Ag(I) and Zn(II) complexes in the gas
      phase.
AB  - Infrared multiple-photon dissociation (IR-MPD) spectroscopy has been applied to
      singly-charged complexes involving the transition metals Ag(+) and Zn(2+) with
      the aromatic amino acid phenylalanine. These studies are complemented by DFT
      calculations. For [Phe+Ag](+) the calculations favor a tridentate charge
      solvation N/O/ring structure. The experimental spectrum strongly supports this as
      the predominant binding geometry and, in particular, rules out a significant
      presence of the salt-bridge conformation. Zn(2+) forms a deprotonated dimer
      complex with Phe, [Zn+Phe(2)-H](+), in which the +2 oxidation state serves as a
      useful biomimetic model for zinc protein sites. A number of low-energy
      conformations were located, of which the lowest-energy conformer predicted by the
      calculations involves a Phe ligand deprotonated on the carboxylic acid, while the
      other Phe ligand is in the tridentate charge solvation conformation. The
      calculated IR spectrum of this conformer gives a close fit to the experimental
      spectrum, strongly supporting this as the predominant binding geometry. This most
      stable calculated complex is characterized by N/ O/ring metal chelation with a
      tetrahedral-type coordination core of Zn(2+) to N and O of both ligands. Another
      similar tightly chelated structure shows a square-planar-type coordination core,
      but this structure is computed to be less stable and gives a less satisfactory
      match to the experimental spectrum. This preference for the tetrahedral geometry
      of the Lewis-basic atomic ligands parallels the common Zn(II) coordination
      geometry in proteins. The number of clearly identifiable peaks resolved in the IR
      MPD spectra as well as the much-improved matches between the observed spectra and
      the DFT-calculated spectra of the most stable geometries compared to previous
      studies are noteworthy for systems of this size and complexity. These results
      demonstrate that IR spectroscopy of transition metal-amino acid complexes in
      combination with DFT calculations is a very powerful structural tool, readily
      applicable to biomimetic systems that model, for example, the reaction centers of
      proteins in the solvent-free environment. In addition, we present a novel ion
      capturing method for Fourier transform ion cyclotron resonance mass spectrometry
      which removes the necessity of a buffer gas pulse, while allowing ion trapping at
      moderate voltages with apparently reduced collisional excitation of the ions.

PMID- 16402840
TI  - Self-organization of rotaxane thin films into spatially correlated
      nanostructures: morphological and structural aspects.
AB  - The self-organization of rotaxane thin films into spatially correlated
      nanostructures is shown to occur upon a thermal stimulus. The mechanism of
      formation of nanostructures and their organization has been investigated using
      atomic force microscopy, bright field transmission electron microscopy, selected
      area electron diffraction, and molecular mechanics simulations. The evolution of
      the nanostructures follows a complex pathway, where a rotaxane thin film first
      dewets from the substrate to form nanosized droplets. Droplets coalesce by
      ripening, generating spatially correlated motifs. In a later stage, the larger
      droplets change shape, nucleate, and coalesce to yield crystallites that grow
      into larger crystals by incorporating the surrounding droplets. The results show
      the following: (i) the nanostructures represent a metastable state of a
      crystallization process; (ii) spatial correlations emerge during ripening, but
      they are destroyed as stable nuclei are formed and crystallization proceeds to
      completion; iii) crystallization, either on graphite or amorphous carbon films,
      leads to a precise basal plane, viz. (010), which has minimum surface energy. The
      inherent degrees of freedom permitted in the rotaxane architecture favors the re
      organization and nucleation of the film in the solid state. Low-energy
      trajectories leading to crystallites with stable surfaces and minimum energy
      contact plane are found to occur via concerted, small amplitude, internal motions
      without disruption of packing and intermolecular contacts.

PMID- 16402841
TI  - Sulfur K-edge XAS and DFT calculations on nitrile hydratase: geometric and
      electronic structure of the non-heme iron active site.
AB  - The geometric and electronic structure of the active site of the non-heme iron
      enzyme nitrile hydratase (NHase) is studied using sulfur K-edge XAS and DFT
      calculations. Using thiolate (RS(-))-, sulfenate (RSO(-))-, and sulfinate
      (RSO(2)(-))-ligated model complexes to provide benchmark spectral parameters, the
      results show that the S K-edge XAS is sensitive to the oxidation state of S
      containing ligands and that the spectrum of the RSO(-) species changes upon
      protonation as the S-O bond is elongated (by approximately 0.1 A). These
      signature features are used to identify the three cysteine residues coordinated
      to the low-spin Fe(III) in the active site of NHase as CysS(-), CysSOH, and
      CysSO(2)(-) both in the NO-bound inactive form and in the photolyzed active form.
      These results are correlated to geometry-optimized DFT calculations. The pre-edge
      region of the X-ray absorption spectrum is sensitive to the Z(eff) of the Fe and
      reveals that the Fe in [FeNO](6) NHase species has a Z(eff) very similar to that
      of its photolyzed Fe(III) counterpart. DFT calculations reveal that this results
      from the strong pi back-bonding into the pi antibonding orbital of NO, which
      shifts significant charge from the formally t(2)(6) low-spin metal to the
      coordinated NO.

PMID- 16402842
TI  - Dynamics of electron transport by elastic bending of short DNA duplexes.
      Experimental study and quantitative modeling of the cyclic voltammetric behavior
      of 3'-ferrocenyl DNA end-grafted on gold.
AB  - The dynamics of electron transport within a molecular monolayer of 3'
      ferrocenylated-(dT)(20) strands, 5'-thiol end-grafted onto gold electrode
      surfaces via a short C2-alkyl linker, is analyzed using cyclic voltammetry as the
      excitation/measurement technique. It is shown that the single-stranded DNA layer
      behaves as a diffusionless system, due to the high flexibility of the ss-DNA
      chain. Upon hybridization by the fully complementary (dA)(20) target, the DNA
      modified gold electrode displays a highly unusual voltammetric behavior, the
      faradaic signal even ultimately switching off at a high enough potential scan
      rate. This remarkable extinction phenomenon is qualitatively and quantitatively
      justified by the model of elastic bending diffusion developed in the present work
      which describes the motion of the DNA-borne ferrocene moiety as resulting from
      the elastic bending of the duplex DNA toward and away from the electrode surface.
      Its use allows us to demonstrate that the dynamics of electron transport within
      the hybridized DNA layer is solely controlled by the intrinsic bending elasticity
      of ds-DNA. Fast scan rate cyclic voltammetry of end-grafted, redox-labeled DNA
      layers is shown to be an extremely efficient method to probe the bending dynamics
      of short-DNA fragments in the submillisecond time range. The persistence length
      of the end-anchored ds-DNA, a parameter quantifying the flexibility of the
      nanometer-long duplex, can then be straightforwardly and accurately determined
      from the voltammetry data.

PMID- 16402843
TI  - Anion-promoted cation motion and conduction in zeolites.
AB  - The motion of sodium cations in sodalite and cancrinite has been investigated by
      force field calculations, solid-state NMR, and impedance spectroscopy. Special
      emphasis is dedicated to the influence of anions on sodium mobilities. Local
      cation motion is promoted when they interact with anions. However, not all
      systems with high local mobilities exhibit good ion conductivities, as
      cooperativity of the motion appears to be an important factor, as well. The
      activation barrier for local sodium motion (calculations) and long-range
      transport (dc conductivities) is lowered in sodalite when halogenide anions, Cl(
      ), Br(-), or I(-), are present. The activation barriers increase with increasing
      size of the anion and decreasing coordination in the transition state. On the
      basis of (23)Na solid-state NMR data, all the sodium ions in the dense sodalite
      structure are rather rigid up to 470 K. All the cations in chromate sodalite, and
      Na(+) in the small cancrinite epsilon-cages without anion interactions, show a
      restricted local motion at higher temperatures. There is a selective high local
      motion of Na(+) in the neighborhood of chromate anions in the more open channel
      system of cancrinite. These results suggest that sodium migration can be
      enhanced, at least locally, in open channel systems by anion interactions. A
      dynamics coupling between anion reorientation and cation mobility was not
      observed.

PMID- 16402844
TI  - Magnetic coupling in dinuclear Gd complexes.
AB  - A spin density functional (SDFT) study of carboxylate-bridged and diazenido
      bridged dinuclear gadolinium compounds is presented. Calculated magnetic coupling
      constants for the carboxylate-bridged structures are in good agreement with
      experimental data, confirming the ability of the broken symmetry approach used in
      this work to predict magnetic behavior in such compounds. The systematic trend
      wherein symmetrically bridged complexes are antiferromagnetically coupled and
      asymmetrically bridged are ferromagnetically coupled is reproduced by the SDFT
      calculations. The mechanism underlying magnetic coupling in closed- and open
      shell dinuclear complexes is described using a perturbative molecular orbital
      model that focuses the influence of the 4f(7)-5d exchange interaction on
      molecular orbitals with significant 5d-orbital character for the complex
      [[[(Me(3)Si)(2)N](2)(thf)Gd](2)(N(2))]. Open-shell electronic configurations
      facilitate strong ferromagnetic coupling, whereas in closed-shell systems
      antiferromagnetic coupling is usually preferred.

PMID- 16402845
TI  - Imaging of ultrafast molecular elimination reactions.
AB  - Ultrafast molecular elimination reactions are studied using the velocity map ion
      imaging technique in combination with femtosecond pump-probe laser excitation. A
      pump laser is used to initiate the dissociative reaction, and after a
      predetermined time delay a probe laser "interrogates" the molecular system. Ionic
      fragments are detected with a two-dimensional velocity map imaging detector
      providing detailed information about the energetic and vectorial properties of
      mass selected photofragments. In this paper we discuss the ultrafast elimination
      of molecular iodine, I(2), from IF(2)C-CF(2)I, where the iodine atoms originate
      from neighboring carbon atoms. By varying the femtosecond delay between pump and
      probe pulse, it is found that elimination of molecular iodine is a concerted
      process, although the two carbon-iodine bonds are not broken synchronously.
      Energetic considerations suggest that the crucial step in this fragmentation
      process is an electron transfer between the two iodine atoms in the parent
      molecule, which leads to Coulombic attraction and the creation of an ion-pair
      state in the molecular iodine fragment.

PMID- 16402846
TI  - Catalytic direct arylation with aryl chlorides, bromides, and iodides:
      intramolecular studies leading to new intermolecular reactions.
AB  - A catalyst for the intramolecular direct arylation of a broad range of simple and
      heterocyclic arenes with aryl iodides, bromides, and chlorides has been
      developed. These reactions occur in excellent yield and are highly selective.
      Studies with aryl iodides substrates revealed that catalyst poisoning occurs due
      to the accumulation of iodide in the reaction media. This can be overcome by the
      addition of silver salts which also permits these reactions to occur at lower
      temperature. The utility of the methodology is illustrated by a rapid synthesis
      of a carbazole natural product and by the synthesis of sterically encumbered
      tetra-ortho-substituted biaryls via ring-opening reactions of the direct
      arylation products. Mechanistic investigations have provided insight into the
      catalyst's mode of action and show the presence of a kinetically significant C-H
      bond cleavage in palladium-catalyzed direct arylation of simple arenes. Knowledge
      garnered from these studies has led to the development of new intermolecular
      arylation reactions with previously inaccessible arenes, opening the door for the
      development of other new direct arylation processes.

PMID- 16402847
TI  - Isotropic-nematic phase transition of single-walled carbon nanotubes in strong
      acids.
AB  - We present the first quantitative assessment of the maximum amount of nanotubes
      that can exist in the isotropic phase () of single-walled carbon nanotubes
      (SWNTs) in Bronsted-Lowry acids. We employ a centrifugation technique in
      conjunction with UV-vis-nIR spectroscopy to quantify , which is also the critical
      concentration of the isotropic-nematic transition of SWNTs in strong acids.
      Centrifugation of biphasic dispersions of SWNTs, that is, acid dispersions
      consisting of an isotropic phase in equilibrium with an ordered nematic liquid
      crystalline phase, results in a clear phase separation, where the isotropic phase
      is supernatant. Dilution of the isotropic phase with a known amount of acid
      followed by UV-vis-nIR absorbance measurements yields , that is, the maximum
      concentration of SWNTs that can exist in the isotropic phase in a given acid for
      a given SWNTs' length distribution. At low SWNT concentration (below 200 ppm) in
      superacids, light absorbance in the range from 400 to 1400 nm scales linearly
      with concentration. This Beer's law behavior yields calibration curves for
      measuring SWNTs' concentration in acids. We find that the critical concentration
      of the isotropic-nematic transition increases with acid strength in accordance
      with the previously proposed sidewall protonation mechanism for dispersing SWNTs
      in acids.

PMID- 16402848
TI  - On the role of tetramethylammonium cation and effects of solvent dynamics on the
      stability of the cage-like silicates Si6O156- and Si8O208- in aqueous solution. A
      molecular dynamics study.
AB  - We have undertaken explicit solvent molecular dynamics simulations to investigate
      the preferential stabilization of the silicate octamer Si(8)O(20)(8-) over the
      hexamer Si(6)O(15)(6-) in relation with the ability of tetramethylammonium (TMA)
      to form an adsorption layer around these cage-like polyions. We have found that
      the hexamer cannot support such a layer and as a result is vulnerable to
      hydrolysis. The dynamics of TMA desorption off the surface of the hexamer is
      investigated in connection with the solvent dynamics. We have studied the
      energetics of this preferential stabilization by calculating the relative change
      in the free energies of formation between the complexes Si(8)O(20)(8-).8TMA and
      Si(6)O(15)(6-).6TMA and found the former to be more stable by 70 kcal/mol. We
      also find that the energetics are consistent with experimental data, suggesting
      that the hexamer is a long-lived metastable species. Furthermore, we have studied
      the solvent structure and dynamics in the vicinity of both the bare polyions and
      their complexes with TMA. We have found that, as anticipated, both the octamer
      and the hexamer participate in hydrogen bonds with the water molecules,
      regardless of whether a TMA adsorption layer exists or not. In fact, we find that
      the presence of a TMA adsorption layer has a rather profound effect on the
      stability of these hydrogen bonds-it increases their lifetime by at least a
      factor of 2 relative to that of the hydrogen bonds between water and the bare
      polyions.

PMID- 16402849
TI  - Singlet excited-state behavior of uracil and thymine in aqueous solution: a
      combined experimental and computational study of 11 uracil derivatives.
AB  - The excited-state properties of uracil, thymine, and nine other derivatives of
      uracil have been studied by steady-state and time-resolved spectroscopy. The
      excited-state lifetimes were measured using femtosecond fluorescence upconversion
      in the UV. The absorption and emission spectra of five representative compounds
      have been computed at the TD-DFT level, using the PBE0 exchange-correlation
      functional for ground- and excited-state geometry optimization and the
      Polarizable Continuum Model (PCM) to simulate the aqueous solution. The
      calculated spectra are in good agreement with the experimental ones. Experiments
      show that the excited-state lifetimes of all the compounds examined are dominated
      by an ultrafast (<100 fs) component. Only 5-substituted compounds show more
      complex behavior than uracil, exhibiting longer excited-state lifetimes and
      biexponential fluorescence decays. The S(0)/S(1) conical intersection, located at
      CASSCF (8/8) level, is indeed characterized by pyramidalization and out of plane
      motion of the substituents on the C5 atom. A thorough analysis of the excited
      state Potential Energy Surfaces, performed at the PCM/TD-DFT(PBE0) level in
      aqueous solution, shows that the energy barrier separating the local S(1) minimum
      from the conical intersection increases going from uracil through thymine to 5
      fluorouracil, in agreement with the ordering of the experimental excited-state
      lifetime.

PMID- 16402850
TI  - Arginine- and lysine-specific polymers for protein recognition and
      immobilization.
AB  - Free radical polymerization of methacrylamide-based bisphosphonates turns weak
      arginine binders into powerful polymeric protein receptors. Dansyl-labeled homo-
      and copolymers with excellent water solubility are accessible through a simple
      copolymerization protocol. Modeling studies point to a striking structural
      difference between the stiff rodlike densely packed homopolymer 1 and the
      flexible copolymer 2 with spatially separated bisphosphonate units. Fluorescence
      titrations in buffered aqueous solution (pH = 7.0) confirm the superior affinity
      of the homopolymer toward oligoarginine peptides reaching nanomolar K(D) values
      for the Tat peptide. Basic proteins are bound almost equally well by 1 and 2 with
      micromolar affinities, with the latter producing much more soluble complexes. The
      Arg selectivity of the monomer is transferred to the polymer, which binds Arg
      rich proteins 1 order of magnitude tighter than lysine-rich pendants of
      comparable pI, size, and (Arg/Lys vs Glu/Asp) ratio. Noncovalent deposition of
      both polymers on glass substrates via polyethyleneimine layers results in new
      materials suitable for peptide and protein immobilization. RIfS measurements
      allow calculation of association constants K(a) as well as dissociation kinetics
      k(D). They generally confirm the trends already found in free solution. Close
      inspection of electrostatic potential surfaces suggest that basic domains favor
      protein binding on the flat surface. The high specificity of the bisphosphonate
      polymers toward basic proteins is demonstrated by comparison with polyvinyl
      sulfate, which has almost no effect in RIfS experiments. Thus, copolymerization
      of few different comonomer units without cross-linking enables surface
      recognition of basic proteins in free solution as well as their effective
      immobilization on surfaces.

PMID- 16402851
TI  - Structure-property correlation of CdSe clusters using experimental results and
      first-principles DFT calculations.
AB  - Structures and properties of CdSe quantum dots (clusters) up to a diameter of
      approximately 2 nm were investigated by combining experimental absorption,
      photoluminescence (PL), and X-ray diffraction (XRD) spectroscopies as well as ab
      initio DFT calculations. These CdSe clusters were nucleated and grown from
      solutions containing respective cadmium and selenium precursors following the hot
      injection technique that allows one to obtain size-controlled CdSe clusters
      having PL efficiency up to 0.5. The DFT calculations were performed at the
      B3LYP/Lanl2dz level and followed by time-dependent TDDFT calculations to estimate
      n energy singlet transitions. On the basis of the results of these experimental
      and theoretical studies, an approach to determine whether the proposed cluster
      with a mean diameter of approximately 2 nm is more physically reasonable is
      discussed. It was shown that the minimum nucleus of a CdSe cluster consists of
      (CdSe)(3) with a six-membered ring and planar structure. No PL is observed for
      this structure. The formation of the next stable cluster depends on whether
      hexadecylamine (HDA) was used for the growth of the CdSe clusters. In the absence
      of HDA, the second cluster was found to be (CdSe)(6) characterized by a broad PL
      spectrum, while in the presence of HDA, it was found to be (CdSe)(n) (where n >
      or = 14) with a sharp PL spectrum.

PMID- 16402852
TI  - Host-guest complexes between an aromatic molecular tweezer and symmetric and
      unsymmetric dendrimers with a 4,4'-bipyridinium core.
AB  - We have investigated the spectroscopic and electrochemical behavior of symmetric
      and unsymmetric first-, second-, and third-generation dendrimers comprising an
      electron-acceptor 4,4'-bipyridinium core (viologen type) and electron-donor 1,3
      dimethyleneoxybenzene (Frechet-type) dendrons. The quite strong fluorescence of
      the symmetrically and unsymmetrically disubstituted 1,3-dimethyleneoxybenzene
      units of the dendrons is completely quenched as a result of donor-acceptor
      interactions that are also evidenced by a low-energy tail in the absorption
      spectrum. In dichloromethane solution, the 4,4'-bipyridinium cores of the
      investigated dendrimers are hosted by a molecular tweezer comprising a
      naphthalene and four benzene components bridged by four methylene units. Host
      guest formation causes the quenching of the tweezer fluorescence. The association
      constants, as measured from fluorescence and (1)H NMR titration plots, (i) are of
      the order of 10(4) M(-1), (ii) decrease on increasing dendrimer generation, and
      (iii) are slightly larger for the unsymmetric than for the symmetric dendrimer of
      the same generation. The analysis of the complexation-induced shifts of the
      temperature-dependent (1)H NMR signals of the host and guest protons confirms
      that the bipyridinium core is positioned inside the tweezer cavity and allows the
      conclusions that (i) shuttling of the tweezer from one to the other pyridinium
      ring is fast (DeltaG < 10 kcal/mol), (ii) in the case of the unsymmetric
      dendrimers, the less substituted pyridinium ring is preferentially complexed in
      apolar solvents, and (iii) complexation of the 4,4'-bipyridinium core proceeds by
      clipping for the symmetric dendrimers and by threading in the case of unsymmetric
      ones. Host-guest formation causes a displacement of the first reduction wave of
      the 4,4'-bipyridinium unit toward more negative potential values, whereas the
      second reduction wave is unaffected. These results show that the host-guest
      complexes between the tweezer and the dendrimers are stabilized by electron donor
      acceptor interactions and can be reversibly assembled/disassembled by
      electrochemical stimulation.

PMID- 16402853
TI  - Influence of intermolecular orientation on the photoinduced charge transfer
      kinetics in self-assembled aggregates of donor-acceptor arrays.
AB  - The kinetics of photoinduced charge transfer reactions in covalently linked donor
      acceptor molecules often undergoes dramatic changes when these molecules self
      assemble from a molecular dissolved state into a nanoaggregate. Frequently, the
      origin of these changes is only partially understood. In this paper, we describe
      the intermolecular spatial organization of three homologous arrays, consisting of
      a central perylene bisimide (PERY) acceptor moiety and two oligo(p-phenylene
      vinylene) (OPV) donor units, in nanoaggregates and identify both face-to-face (H
      type) and slipped (J-type) stacking of the OPV and PERY chromophores. For the J
      type aggregates, short intermolecular OPV-PERY distances are created that give
      rise to a charge-transfer absorption band. The proximity of the donor and
      acceptor groups in the J-type aggregates enables a highly efficient photoinduced
      charge separation with a rate (k(cs) > 10(12) s(-1)) that significantly exceeds
      the rate of the intramolecular charge transfer of the same compounds when
      molecularly dissolved, even in the most polar media. In the H-type aggregates, on
      the other hand, the intermolecular OPV-PERY distance is not reduced compared to
      the intramolecular separation, and hence, the rates of the electron transfer
      reactions are not significantly affected compared to the molecular dissolved
      state. Similar to the forward electron transfer, the kinetics of the charge
      recombination in the aggregated state can be understood by considering the
      different interchromophoric distances that occur in the H- and J-type aggregates.
      These results provide the first consistent rationalization of the remarkable
      differences that are observed for photoinduced charge-transfer reactions of donor
      acceptor compounds in molecularly dissolved versus aggregated states.

PMID- 16402854
TI  - DNA hole transport on an electrode: application to effective photoelectrochemical
      SNP typing.
AB  - A useful feature of DNA is that long-range hole transport through DNA is readily
      achieved. Photostimulated long-range hole transport through DNA has prospective
      use in the development of a conceptually new electrochemical single-nucleotide
      polymorphism (SNP) typing method for use as a versatile platform for gene
      diagnostics and pharmacogenetics. We have applied artificial DNAs designed for
      photostimulated long-range hole transport through DNA to SNP typing. By
      hybridizing photosensitizer-equipped DNA probes, immobilized on gold working
      electrodes, with a target DNA strand containing an SNP site, we observed a
      cathodic photocurrent, which markedly changed depending on the nature of the base
      at the specific site. The use of a combination of hole-transporting bases
      constitutes a very powerful method for a single-step electrochemical assay
      applicable to SNP typing of all types of sequences.

PMID- 16402857
TI  - Atypical membrane topology and heteromeric function of Drosophila odorant
      receptors in vivo.
AB  - Drosophila olfactory sensory neurons (OSNs) each express two odorant receptors
      (ORs): a divergent member of the OR family and the highly conserved, broadly
      expressed receptor OR83b. OR83b is essential for olfaction in vivo and enhances
      OR function in vitro, but the molecular mechanism by which it acts is unknown.
      Here we demonstrate that OR83b heterodimerizes with conventional ORs early in the
      endomembrane system in OSNs, couples these complexes to the conserved ciliary
      trafficking pathway, and is essential to maintain the OR/OR83b complex within the
      sensory cilia, where odor signal transduction occurs. The OR/OR83b complex is
      necessary and sufficient to promote functional reconstitution of odor-evoked
      signaling in sensory neurons that normally respond only to carbon dioxide.
      Unexpectedly, unlike all known vertebrate and nematode chemosensory receptors, we
      find that Drosophila ORs and OR83b adopt a novel membrane topology with their N
      termini and the most conserved loops in the cytoplasm. These loops mediate direct
      association of ORs with OR83b. Our results reveal that OR83b is a universal and
      integral part of the functional OR in Drosophila. This atypical heteromeric and
      topological design appears to be an insect-specific solution for odor
      recognition, making the OR/OR83b complex an attractive target for the development
      of highly selective insect repellents to disrupt olfactory-mediated host-seeking
      behaviors of insect disease vectors.

PMID- 16402858
TI  - Critical role of gap junction coupled KATP channel activity for regulated insulin
      secretion.
AB  - Pancreatic beta-cells secrete insulin in response to closure of ATP-sensitive K+
      (KATP) channels, which causes membrane depolarization and a concomitant rise in
      intracellular Ca2+ (Cai). In intact islets, beta-cells are coupled by gap
      junctions, which are proposed to synchronize electrical activity and Cai
      oscillations after exposure to stimulatory glucose (>7 mM). To determine the
      significance of this coupling in regulating insulin secretion, we examined islets
      and beta-cells from transgenic mice that express zero functional KATP channels in
      approximately 70% of their beta-cells, but normal KATP channel density in the
      remainder. We found that KATP channel activity from approximately 30% of the beta
      cells is sufficient to maintain strong glucose dependence of metabolism, Cai,
      membrane potential, and insulin secretion from intact islets, but that glucose
      dependence is lost in isolated transgenic cells. Further, inhibition of gap
      junctions caused loss of glucose sensitivity specifically in transgenic islets.
      These data demonstrate a critical role of gap junctional coupling of KATP channel
      activity in control of membrane potential across the islet. Control via coupling
      lessens the effects of cell-cell variation and provides resistance to defects in
      excitability that would otherwise lead to a profound diabetic state, such as
      occurs in persistent neonatal diabetes mellitus.

PMID- 16402859
TI  - Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7:
      implications for the regulation of the p53-MDM2 pathway.
AB  - Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), a
      deubiquitylating enzyme of the ubiquitin-specific processing protease family,
      specifically deubiquitylates both p53 and MDM2, hence playing an important yet
      enigmatic role in the p53-MDM2 pathway. Here we demonstrate that both p53 and
      MDM2 specifically recognize the N-terminal tumor necrosis factor-receptor
      associated factor (TRAF)-like domain of HAUSP in a mutually exclusive manner.
      HAUSP preferentially forms a stable HAUSP-MDM2 complex even in the presence of
      excess p53. The HAUSP-binding elements were mapped to a peptide fragment in the
      carboxy-terminus of p53 and to a short-peptide region preceding the acidic domain
      of MDM2. The crystal structures of the HAUSP TRAF-like domain in complex with p53
      and MDM2 peptides, determined at 2.3-A and 1.7-A resolutions, respectively,
      reveal that the MDM2 peptide recognizes the same surface groove in HAUSP as that
      recognized by p53 but mediates more extensive interactions. Structural comparison
      led to the identification of a consensus peptide-recognition sequence by HAUSP.
      These results, together with the structure of a combined substrate-binding-and
      deubiquitylation domain of HAUSP, provide important insights into regulation of
      the p53-MDM2 pathway by HAUSP.

PMID- 16402860
TI  - Attenuation of self-generated tactile sensations is predictive, not postdictive.
AB  - When one finger touches the other, the resulting tactile sensation is perceived
      as weaker than the same stimulus externally imposed. This attenuation of
      sensation could result from a predictive process that subtracts the expected
      sensory consequences of the action, or from a postdictive process that alters the
      perception of sensations that are judged after the event to be self-generated. In
      this study we observe attenuation even when the fingers unexpectedly fail to make
      contact, supporting a predictive process. This predictive attenuation of self
      generated sensation may have evolved to enhance the perception of sensations with
      an external cause.

PMID- 16402861
TI  - Inhibitory effects of mizolastine on ultraviolet B-induced leukotriene B4
      production and 5-lipoxygenase expression in normal human dermal fibroblasts in
      vitro.
AB  - Ultraviolet B (UVB) irradiation exerts hazardous effects such as acute
      photodamage, skin cancer and photoaging. In this study we evaluated the
      protective effects of a nonsedative histamine H1-receptor antagonist,
      mizolastine, on UVB-exposed skin dermal fibroblasts. Therefore, primary human
      skin fibroblasts were incubated with mizolastine or dexamethasone after 100
      mJ/cm(2) UVB irradiation. Leukotriene B4 (LTB4) in fibroblast supernatants was
      detected with enzyme immunoassays, expression of 5-lipoxygenase (5-LOX) messenger
      RNA (mRNA) in skin fibroblasts was examined by reverse transcriptase-polymerase
      chain reaction and expression of 5-LOX protein was measured by immune blotting
      and immunofluorescent staining with rabbit anti-human 5-LOX antibody. It was
      found that 0.01 mM mizolastine inhibited UVB-induced LTB4 production from skin
      fibroblasts at 12, 24 and 36 h. Meanwhile, mizolastine down-regulated 5-LOX mRNA
      expression and inhibited 5-LOX translocation from nucleus to cytoplasm in
      fibroblasts. On the basis of these findings, we propose that mizolastine might
      play a protective role in the pathogenesis of UV radiation-induced acute
      photodamage of the skin.

PMID- 16402862
TI  - Sibling relationship contributions to individual and family well-being:
      introduction to the special issue.
AB  - This special issue presents new findings that illustrate the ways in which
      sibling relationships serve as important contexts for individual development and
      family functioning. This collection of articles, which emphasizes effects on both
      normative and at-risk development, is intended to stimulate further research on
      the multifaceted and often contradictory contributions siblings extend to one
      another across the life course.

PMID- 16402863
TI  - Preschool children's interactions with friends and older siblings: relationship
      specificity and joint contributions to problem behavior.
AB  - The primary aim of the present study was to examine the extent to which friend
      and sibling relationship quality jointly contribute to children's behavioral
      adjustment. Preschool-aged children (N = 52) were observed separately with a
      friend and an older sibling during a free-play session and a sharing task. Mean
      comparisons indicated that friendship dyads, on average, engaged in more complex
      social play and more intense conflict (but only during free play), whereas
      sibling dyads were characterized by greater asymmetry. Few friend-sibling
      associations emerged. Friend and sibling relationship quality in the sharing task
      together accounted for a significant portion of variance in parent-reported
      aggressive-disruptive behavior, and a Sibling x Friend interaction indicated that
      greater relationship quality with one partner buffered children from poor
      behavioral adjustment when relationship quality with the other partner was low or
      moderate. Implications for preventive intervention efforts are discussed.

PMID- 16402864
TI  - Playmates and teachers: reciprocal and complementary interactions between
      siblings.
AB  - Associations between siblings' reciprocal (i.e., play) and complementary (i.e.,
      teaching) interactions in 70 sibling dyads (1st-born siblings' mean age=81.6
      months, range=59-119 months; 2nd-born siblings' mean age = 56.1 months, range = 5
      79 months) were examined. Dyads participated in 2 sessions (play, teaching) and
      completed a sibling relationship quality measure. Findings revealed modest
      associations across play and teaching sessions; for example, greater learner
      involvement in the teaching task was associated with more collaboration and less
      negative affect during play. In addition, the 2nd-born's teaching style was
      related to perceptions of relationship quality. Results indicate that reciprocal
      and complementary types of interactions may provide important contexts for
      development of individual differences in dyadic and individual behaviors and may
      afford opportunities for siblings to influence one another's development.

PMID- 16402865
TI  - Sibling relationship quality from birth to adolescence: the enduring
      contributions of friends.
AB  - The purpose of the present study was to examine continuity in sibling
      relationships across childhood and to evaluate the degree to which children's
      experiences with their friends and mothers prior to their sibling's birth predict
      the quality of the relationship they establish with their siblings in
      adolescence. Twenty-eight firstborn children, who were 48 months old at the time
      of their sibling's birth, were observed interacting with their siblings and
      friends at multiple time points. The level of positive social behaviors
      demonstrated in their early relationships with friends continued to predict
      sibling relationship quality in adolescence. Firstborn children who had more
      positive interactions with friends prior to their sibling's birth demonstrated
      more prosocial interactions with both their siblings and friends in adolescence
      and exhibited fewer externalizing behaviors. Longitudinal associations support
      the hypothesis that the social competencies that young children demonstrate in
      their early relationships with friends may have enduring significance for their
      social development.

PMID- 16402866
TI  - Adolescent sibling relationships in Mexican American families: exploring the role
      of familism.
AB  - To address a significant gap in the literature on normative processes in minority
      families, the authors studied adolescents' sibling relationships in two-parent
      Mexican American families and explored connections between sibling relationship
      characteristics and familism. Participants were 246 adolescent Mexican American
      sibling pairs who participated in (a) home interviews during which adolescents
      described their sibling relationships and familism values and (b) a series of 7
      nightly phone calls during which adolescents reported their daily activities,
      including time spent with siblings and family members. Siblings described their
      relationships as both intimate and conflictual, and daily activity data revealed
      that they spent an average of 17.2 hr per 7 days in shared activities. Sibling
      relationship qualities were linked to familism values and practices, and stronger
      patterns of association emerged for sisters than brothers. Discussion highlights
      the significance of studying the processes that underlie within-group variations
      among families of different cultural backgrounds.

PMID- 16402867
TI  - Sibling relationships in early/middle childhood: links with individual
      adjustment.
AB  - The overarching goal of the study was to identify links between sibling
      relationship quality in early/middle childhood with children's adjustment, having
      accounted for the effects of parent-child relationship quality. The sample
      consisted of 101 working and middle-class 2-parent English families with 2
      children ages 4-8 years. Parents provided reports of sibling relationship
      quality, the parent-child relationship, and the children's prosocial and
      problematic behaviors. The children also provided reports of their familial
      relationships with a puppet interview. Results indicated that sibling
      relationship quality was associated with the older siblings' adjustment,
      controlling for the children's relationships with parents. In addition, the
      pattern of findings suggested that positivity within the sibling relationship was
      more strongly linked with child adjustment than was sibling conflict.

PMID- 16402868
TI  - Change in maternal perception of sibling negativity: within- and between-family
      influences.
AB  - Change in maternal report of sibling negativity was investigated in 313 sibling
      dyads from 171 families taking part in a longitudinal, general population survey
      in the United Kingdom. The inclusion of multiple dyads per family allowed for the
      emergence of 3 novel elements for sibling research: an examination of within
      family similarity on sibling relationship quality, modeling within-family
      similarity as a function of the shared environment and the differentiation of
      family-wide and dyad-specific predictors. Moderate similarity on sibling
      negativity was found across different sibling dyads and similarity was higher in
      2 versus lone-parent families. Maternal negativity, genetic relatedness, age of
      the oldest child in the dyad, and the interaction between lone-parent status and
      maternal differential treatment were found to predict change in sibling
      negativity.

PMID- 16402869
TI  - The transition to siblinghood: a developmental ecological systems perspective and
      directions for future research.
AB  - The birth of a baby sibling is a normative life event for many children. Few
      studies address this important transition period and changes in the older
      sibling's adjustment and family relationships following the sibling's birth. The
      present article presents a developmental ecological systems model for studying
      changes in family life and the older child's adjustment following the birth of a
      baby sibling. Simultaneous changes occurring in the family and how these changes
      are interrelated over time to predict patterns of adaptation after the transition
      to siblinghood are underscored. Recommendations for designing longitudinal
      studies that take advantage of recent developments in multilevel modeling are
      also discussed.

PMID- 16402870
TI  - Longitudinal associations between sibling relationship quality, parental
      differential treatment, and children's adjustment.
AB  - This study examined associations between changes in sibling relationships and
      changes in parental differential treatment and corresponding changes in
      children's adjustment. One hundred thirty-three families were assessed at 3 time
      points. Parents rated children's externalizing problems, and children reported on
      sibling relationship quality, parental differential treatment, and depressive
      symptoms. On average, older siblings were 10, 12, and 16 years old, and younger
      siblings were 8, 10, and 14 years old at Waves 1, 2, and 3, respectively. Results
      from hierarchical linear modeling indicated that as sibling relationships
      improved over time, children's depressive symptoms decreased over time. In
      addition, as children were less favored over their siblings over time, children's
      externalizing problems increased over time. Findings highlight the developmental
      interplay between the sibling context and children's adjustment.

PMID- 16402871
TI  - Families and risk: prospective analyses of familial and social influences on
      adolescent substance use.
AB  - Parental, peer, and older siblings' contributions to adolescents' substance use
      were investigated with 2 waves of panel data from 225 African American families.
      Structural equation modeling showed that older siblings' behavioral willingness
      (BW) to use substances at Time 1 (T1) predicted target adolescents' Time 2 (T2)
      use, controlling for other T1 variables. Regression analyses revealed an
      interaction between targets' and siblings' BW, such that targets were more likely
      to use at T2 if both they and their siblings reported BW at T1. This interaction
      was stronger for families living in high-risk neighborhoods. Finally, siblings'
      willingness buffered the impact of peer use on targets' later use: Low sibling BW
      was associated with less evidence of peer influence.

PMID- 16402872
TI  - Longitudinal pathways linking family factors and sibling relationship qualities
      to adolescent substance use and sexual risk behaviors.
AB  - This 3-wave, 5-year longitudinal study tested the contributions of family
      contextual factors and sibling relationship qualities to younger siblings'
      substance use, sexual risk behaviors, pregnancy, and sexually transmitted
      disease. More than 220 non-White families participated (67% Latino and 33%
      African American), all of which involved a younger sibling (133 girls and 89
      boys; mean age = 13.6 years at Time 1) and an older sister (mean age = 17 years
      at Time 1). Results from structural equation latent growth curve modeling
      indicated that qualities of the sibling relationship (high older sister power,
      low warmth/closeness, and low conflict) mediated effects from several family
      risks (mothers' single parenting, older sisters' teen parenting, and family's
      receipt of aid) to younger sibling outcomes. Model results were generally
      stronger for sister-sister pairs than for sister-brother pairs. Findings add to
      theoretical models that emphasize the role of family and parenting processes in
      shaping sibling relationships, which, in turn, influence adolescent outcomes.

PMID- 16402873
TI  - Older siblings benefit from a family-based preventive intervention for
      preschoolers at risk for conduct problems.
AB  - This study evaluated sibling effects of a family-based intervention aimed at
      preventing conduct problems in preschool-age siblings of adjudicated youths.
      Ninety-two families of preschoolers who had older siblings adjudicated for
      delinquent acts were randomly assigned to intervention and control conditions. Of
      these, 47 families had nontargeted school-age (5-11 years) or adolescent siblings
      (12-17 years) living at home. These families were considered in this report. The
      authors hypothesized group differences on antisocial behavior and positive peer
      relations for older siblings of targeted preschoolers. The authors examined
      outcomes of parent- and teacher-reported behavior immediately postintervention
      and 8 months postintervention. Findings revealed significant intervention effects
      8 months following intervention for adolescent siblings on parent-reported
      antisocial behavior and positive peer relations. Teacher reports confirmed group
      differences for antisocial behavior immediately postintervention. Findings
      document benefits for adolescent siblings.

PMID- 16402874
TI  - Sibling relationships as contexts for delinquency training in low-income
      families.
AB  - The purpose of the study was to investigate the link between sibling
      relationships and antisocial behavior in 208 boys from low-income families.
      Sibling relational attributes and mother-target child (MTC) relationship quality
      were assessed when the target child (TC) was 10 years old. At ages 11 and 12, TC
      antisocial behavior and TC reports of peer antisocial behavior were evaluated.
      Results indicated that MTC negative relationship quality was significantly
      related to sibling conflict. In turn, sibling conflict was a significant
      predictor of antisocial behavior; sibling warmth/closeness was related to TC
      reports of peer antisocial behavior. Findings also indicated that sibling
      relationship quality was related to antisocial behavior after controlling for MTC
      negativity. Implications for interventions are discussed.

PMID- 16402875
TI  - Differential association of family subsystem negativity on siblings'
      maladjustment: using behavior genetic methods to test process theory.
AB  - This study investigated the family context of adolescent sibling similarity and
      differentiation in maladjustment (antisocial behavior and depression) by
      examining negativity in different subsystems. Two hypotheses were proposed: (1)
      Parental and sibling negativity tends to diffuse through the family system,
      especially because of the high level of reciprocity in sibling relationships,
      leading to sibling similarity; and (2) interparental (coparenting) conflict
      disrupts cohesive functioning and thereby motivates and facilitates sibling
      differentiation and niche picking. To control for the effects of similar genes
      between siblings, the authors used behavioral genetic models with a genetically
      informed sample of 720 two-parent families, each with at least 2 adolescent
      siblings. Results for the differences in shared environmental influences across
      groups high and low in each of the domains of family negativity provided partial
      support for the hypotheses. The results further understanding of influences on
      individual differences and support a theory of how parent-child and interparental
      relationships intersect with sibling relationship dynamics.

PMID- 16402876
TI  - Sibling effects on substance use in adolescence: social contagion and genetic
      relatedness.
AB  - Prior research on sibling contagion for substance use has not attended to
      individual differences in the sibling relationship that may be influenced by
      genetic similarity. The authors utilizing data on a sample of twin and nontwin
      siblings participating in the National Longitudinal Study of Adolescent Health
      (Add Health). Although monozygotic twins had the highest levels of sibling
      contact and mutual friendships, the pattern of results for other sibling types
      were not consistent with genetic models, and biometric analysis indicated that
      shared environmental factors influenced these sibling relationship features.
      Application of DeFries-Fulker regression models provided evidence that sibling
      contact and mutual friendships represent a source of social contagion for
      adolescent smoking and drinking independent of genetic relatedness. The results
      are interpreted using a social contagion framework and contrasted with other
      competing models such as those focused on the equal environments assumption and
      niche selection.

PMID- 16402877
TI  - A retrospective study of risk to siblings in abusing families.
AB  - Relatively little research has considered the risk to siblings within maltreating
      families. The sample in the present study consisted of the 795 siblings from a
      cohort of 400 "index" children who had been referred to police child protection
      units in England for abuse and/or neglect. In 44% of families (valid cases), the
      index child was scapegoated, in 37% maltreatment was nonspecific to all siblings,
      and in 20% maltreatment was specifically directed at some but not all siblings.
      Scapegoated children were more likely to be older and to experience physical or
      sexual abuse, whereas younger children and index child referrals for neglect,
      emotional abuse, or mixed abuse were associated with risk to some or all
      siblings. Parental difficulties and family stressors increased the risk of
      maltreatment to all siblings. There was no evidence of increased risk to
      stepsiblings or children with difficulties, suggesting that the special victim
      model has limited application.

PMID- 16402878
TI  - Latino sibling knowledge and adjustment to chronic disability.
AB  - Forty matched healthy Latino and non-Latino siblings (ages 8-14 years) of
      children with developmental and physical disabilities completed interviews and
      questionnaires assessing sibling knowledge of and adjustment to disability and
      sibling global psychological functioning. One-way analyses of variance revealed
      Latino siblings to have significantly less accurate information about the
      disability and more internalizing problems than non-Latino siblings. Sibling and
      parent wishes for the healthy sibling reflected cultural values. The results
      indicate that Latino siblings of children with chronic disabilities may be at
      risk for internalizing psychological problems. Future research regarding cultural
      factors affecting sibling adaptation to childhood disability is encouraged.

PMID- 16402879
TI  - Reciprocal links among differential parenting, perceived partiality, and self
      worth: a three-wave longitudinal study.
AB  - This study examined reciprocal links between parental differential treatment,
      siblings' perception of partiality, and self-worth with 3 waves of data from 384
      adolescent sibling dyads. Results suggest that birth-order status was
      significantly associated with self-worth and perception of maternal and paternal
      differential treatment. There was a consistent across-time effect of self-worth
      on perception of parental partiality for later born siblings, but not earlier
      born siblings, and a consistent effect of differential treatment on perception of
      partiality for earlier born but not later born siblings. The results contribute
      new insight into the associations between perception of differential parenting
      and adolescents' adjustment and the role of birth order.

PMID- 16402880
TI  - The consequences of antisocial behavior in older male siblings for younger
      brothers and sisters.
AB  - The contribution of younger male and female siblings' conflict and involvement in
      deviant activities with their older brothers to younger siblings' adolescent
      adjustment problems was examined in the context of parenting. Ineffective
      parenting during younger siblings' childhood had no direct effects on adjustment
      but facilitated their exposure to older brothers' deviant peers and activities.
      The effect of sibling conflict on adjustment was mediated by younger siblings'
      coparticipation in deviant activities with their older brothers during
      adolescence. Early sibling conflict and coparticipation in deviant activities
      synergistically increased the risk for younger siblings' adolescent adjustment
      problems. These empirical relations held in the context of parental discipline of
      younger siblings during adolescence. Sibling relationships entail a set of
      iterative social processes that strongly influence risk for adolescent antisocial
      behavior, drug use, sexual behavior, and traumatic experience. Variations in
      sibling influence were observed conditional on the gender combination of the
      sibling pair and on sibling age differences.

PMID- 16402881
TI  - Commentary: siblings in their families.
AB  - Three themes in the contributions to the Special Issue are discussed. The first
      is new evidence for associations between the quality of sibling relationships and
      children's adjustment problems and positive development, from research which also
      takes account of parent-child relationships, and genetic associations. The second
      is the new methodological approaches to studying the complexity of family
      patterns in which siblings play a central role (for instance with multilevel
      modelling) and the study of changes over time. The third is the significance of
      connections with relationships outside the family especially peer relationships
      and friendships.

PMID- 16402883
TI  - Preparing medical graduates for general practice.

PMID- 16402884
TI  - Value-based insurance design: a "clinically sensitive" approach to preserve
      quality of care and contain costs.

PMID- 16402885
TI  - Varying pharmacy benefits with clinical status: the case of cholesterol-lowering
      therapy.
AB  - OBJECTIVE: To determine whether a pharmacy benefit that varies copayments for
      cholesterol-lowering (CL) therapy according to expected therapeutic benefit would
      improve compliance and reduce use of other services. METHODS: Using claims data
      from 88 health plans, we studied 62 274 patients aged 20 years and older who
      initiated CL therapy between 1997 and 2001. We examined the association between
      copayments and compliance in the year after initiation of therapy, and the
      association between compliance and subsequent hospital and emergency department
      (ED) use for up to 4 years after initiation. RESULTS: The fraction of fully
      compliant patients fell by 6 to 10 percentage points when copayments increased
      from 10 dollars to 20 dollars, depending on patient risk (P < .05). Full
      compliance was associated with 357 fewer hospitalizations annually per 1000 high
      risk patients (P < .01) and 168 fewer ED visits (P < .01) compared with patients
      not in full compliance. For patients at low risk, full compliance was associated
      with 42 fewer hospitalizations (P = .02) and 21 fewer ED visits (P = .22). Using
      these results, we simulated a policy that eliminated copayments for high- and
      medium-risk patients but raised them (from 10 dollars to 22 dollars) for low-risk
      patients. Based on a national sample of 6.3 million adults on CL therapy, this
      policy would avert 79,837 hospitalizations and 31,411 ED admissions annually.
      CONCLUSION: Although many obstacles exist, varying copayments for CL therapy by
      therapeutic need would reduce hospitalizations and ED use--with total savings of
      more than 1 billion dollars annually.

PMID- 16402886
TI  - Do drug formulary policies reflect evidence of value?
AB  - OBJECTIVE: To investigate the extent to which preferred drug lists and tiered
      formularies reflect evidence of value, as measured in published cost-utility
      analyses (CUAs). METHODS: Using 1998-2001 data from a large registry of cost
      effectiveness analyses, we examined the 2004 Florida Medicaid preferred drug list
      and the 2004 Harvard Pilgrim Pharmacy Program 3-tier formulary, and compared cost
      utility ratios (standardized to 2002 US dollars) of drugs with preferred and
      nonpreferred status. RESULTS: Few drugs on the formularies had any cost-utility
      data available. Of those that did, median cost-utility ratios were somewhat
      higher (less favorable) for Florida's preferred drugs compared with the
      nonpreferred drugs (25,465 dollars vs 13,085 dollars; P = .09). Ratios did not
      differ for drugs on tiers 1 and 2 of the Harvard Pilgrim formulary, although they
      were higher for tier 3 and for excluded drugs (18,309 dollars, 18,846 dollars,
      52,119 dollars, and 22,580 dollars, respectively; P = .01). Among therapies
      reported to be cost-saving or to have cost-utility ratios below 50,000 dollars,
      77% had favored status in Florida Medicaid and 73% in Harvard Pilgrim. Among
      dominated drug interventions (reported to be more costly and less effective than
      alternatives), 95% had favored status in Florida Medicaid and 56% in Harvard
      Pilgrim. CONCLUSIONS: This study underscores the paucity of published cost
      utility data available to formulary committees. Some discrepancies prevail
      between the value of drugs, as reflected in published cost-utility ratios, and
      the formulary placement policies of 2 large health plans.

PMID- 16402887
TI  - Medicare and Medicaid managed care: a tale of two trajectories.
AB  - Two decades of efforts to promote managed care models in Medicare and Medicaid
      have resulted in vastly different experiences as measured by enrollment, plan
      participation, and ability to achieve the goals of public policy-makers. The
      Medicare Modernization Act of 2003 introduced a major transformation to engage
      and retain private health plans. It is useful for plan administrators to consider
      why the trajectories for the programs have been so divergent and to assess
      prospects for success in the Medicare Advantage initiative.

PMID- 16402888
TI  - Who will be denied Medicare prescription drug subsidies because of the asset
      test?
AB  - OBJECTIVE: To determine the number and characteristics of Medicare beneficiaries
      who will be excluded from low-income prescription drug subsidies because they do
      not qualify under an asset test. STUDY DESIGN: Cross-sectional, using the US
      Census Bureau's Survey of Income and Program Participation (SIPP); results were
      based on interviews occurring between October 2002 and January 2003. The sample
      included 9278 Medicare beneficiaries, 2929 with incomes below 150% of the federal
      poverty level (FPL). METHODS: Using SIPP, each sample member's income was
      compared to the FPL. Income was adjusted to include only liquid assets and
      primary residences. The number of individuals excluded by the asset test and
      their characteristics and types of assets responsible were calculated. RESULTS:
      Of 13.97 million noninstitutionalized Medicare beneficiaries, 2.37 million (17%)
      with low incomes would be excluded from subsidized drug coverage due to the asset
      test. Compared to higher-income beneficiaries, the excluded individuals tended to
      be older, female, widowed, and living alone. Almost half of their assets were
      checking and savings accounts. Half of the individuals failing the test had
      assets less than 35,000 dollars above the allowing thresholds. CONCLUSIONS:
      Widows are disproportionately affected by the asset test. When a husband dies,
      income plummets but accumulated assets often exceed those allowed under Medicare
      legislation. During their working years Americans are encouraged to save for
      retirement, but by accumulating modest amounts of assets, these same people often
      will then not qualify for low-income drug subsidies. Modifying or eliminating the
      asset test would help protect individuals disadvantaged by low incomes who have
      modest amounts of asset holdings.

PMID- 16402889
TI  - Medicare HMO penetration and mortality outcomes of ischemic stroke.
AB  - OBJECTIVE: To examine associations between Medicare health maintenance
      organization (HMO) penetration and stroke mortality outcomes among older persons.
      STUDY DESIGN: Panel analysis of nationally representative secondary data from
      1993 to 1998. METHODS: The first analysis sample included ischemic stroke
      hospitalizations among older persons in the Nationwide Inpatient Sample; the
      second included county-level ischemic stroke deaths in the National Vital
      Statistics System. The 2 samples were merged with the HMO enrollment data and the
      2001 Area Resource File. The 2 outcomes were in hospital death status and county
      level population ischemic stroke death rates among older persons; the 2
      utilization variables were length of hospital stay for ischemic stroke and
      proportion of ischemic stroke deaths occurring in hospitals. The 3 key
      explanatory variables were county-level Medicare total, independent practice
      association, and nonindependent practice association HMO penetration. Ordinary
      least squares analysis with hospital or county fixed effects was used in
      estimation. RESULTS: Medicare HMO penetration was not associated with the 2
      ischemic stroke mortality outcomes (P > .05). Increases in Medicare total and
      independent practice association HMO penetration were associated with a
      significant shift in a higher proportion of stroke deaths from hospitals to
      nursing homes or residences (P < .05). Medicare HMO penetration was negatively
      associated with length of stay, although this was not statistically significant
      (P > .05). CONCLUSIONS: Increased Medicare HMO penetration was associated with a
      shift in ischemic stroke deaths from hospitals to nonhospital settings. The
      effect of Medicare HMO penetration on quality of stroke care needs further
      research.

PMID- 16402891
TI  - Proteogenomic approaches for the molecular characterization of natural microbial
      communities.
AB  - At the present time we know little about how microbial communities function in
      their natural habitats. For example, how do microorganisms interact with each
      other and their physical and chemical surroundings and respond to environmental
      perturbations? We might begin to answer these questions if we could monitor the
      ways in which metabolic roles are partitioned amongst members as microbial
      communities assemble, determine how resources such as carbon, nitrogen, and
      energy are allocated into metabolic pathways, and understand the mechanisms by
      which organisms and communities respond to changes in their surroundings. Because
      many organisms cannot be cultivated, and given that the metabolisms of those
      growing in monoculture are likely to differ from those of organisms growing as
      part of consortia, it is vital to develop methods to study microbial communities
      in situ. Chemoautotrophic biofilms growing in mine tunnels hundreds of meters
      underground drive pyrite (FeS(2)) dissolution and acid and metal release,
      creating habitats that select for a small number of organism types. The
      geochemical and microbial simplicity of these systems, the significant biomass,
      and clearly defined biological-inorganic feedbacks make these ecosystem
      microcosms ideal for development of methods for the study of uncultivated
      microbial consortia. Our approach begins with the acquisition of genomic data
      from biofilms that are sampled over time and in different growth conditions. We
      have demonstrated that it is possible to assemble shotgun sequence data to reveal
      the gene complement of the dominant community members and to use these data to
      confidently identify a significant fraction of proteins from the dominant
      organisms by mass spectrometry (MS)-based proteomics. However, there are
      technical obstacles currently restricting this type of "proteogenomic" analysis.
      Composite genomic sequences assembled from environmental data from natural
      microbial communities do not capture the full range of genetic potential of the
      associated populations. Thus, it is necessary to develop bioinformatics
      approaches to generate relatively comprehensive gene inventories for each
      organism type. These inventories are critical for expression and functional
      analyses. In proteomic studies, for example, peptides that differ from those
      predicted from gene sequences can be measured, but they generally cannot be
      identified by database matching, even if the difference is only a single amino
      acid residue. Furthermore, many of the identified proteins have no known
      function. We propose that these challenges can be addressed by development of
      proteogenomic, biochemical, and geochemical methods that will be initially
      deployed in a simple, natural model ecosystem. The resulting approach should be
      broadly applicable and will enhance the utility and significance of genomic data
      from isolates and consortia for study of organisms in many habitats. Solutions
      draining pyrite-rich deposits are referred to as acid mine drainage (AMD). AMD is
      a very prevalent, international environmental problem associated with energy and
      metal resources. The biological-mineralogical interactions that define these
      systems can be harnessed for energy-efficient metal recovery and removal of
      sulfur from coal. The detailed understanding of microbial ecology and ecosystem
      dynamics resulting from the proposed work will provide a scientific foundation
      for dealing with the environmental challenges and technological opportunities,
      and yield new methods for analysis of more complex natural communities.

PMID- 16402892
TI  - Transcriptional signatures of normal human mammary epithelial cells in response
      to benzo[a]pyrene exposure: a comparison of three microarray platforms.
AB  - Microarrays are used to study gene expression in a variety of biological systems.
      A number of different platforms have been developed, but few studies exist that
      have directly compared the performance of one platform with another. The goal of
      this study was to determine array variation by analyzing the same RNA samples
      with three different array platforms. Using gene expression responses to
      benzo[a]pyrene exposure in normal human mammary epithelial cells (NHMECs), we
      compared the results of gene expression profiling using three microarray
      platforms: photolithographic oligonucleotide arrays (Affymetrix), spotted
      oligonucleotide arrays (Amersham), and spotted cDNA arrays (NCI). While most
      previous reports comparing microarrays have analyzed pre-existing data from
      different platforms, this comparison study used the same sample assayed on all
      three platforms, allowing for analysis of variation from each array platform. In
      general, poor correlation was found with corresponding measurements from each
      platform. Each platform yielded different gene expression profiles, suggesting
      that while microarray analysis is a useful discovery tool, further validation is
      needed to extrapolate results for broad use of the data. Also, microarray
      variability needs to be taken into consideration, not only in the data analysis
      but also in specific probe selection for each array type.

PMID- 16402893
TI  - Clusters of adjacent and similarly expressed genes across normal human tissues
      complicate comparative transcriptomic discovery.
AB  - Transcriptomic techniques are valuable tools with which to validate genetic and
      biological hypotheses and are now widely available for research. However, with
      the exception of tumor biology, comparative genomics analyses have been difficult
      to use as discovery engines to describe biologically relevant expression changes.
      We propose that physical proximity of human genes correlates with similar mRNA
      expression, so that increased expression might include a disease-relevant gene
      and many other genes in the adjacent region. To increase the efficiency of
      combining susceptibility gene mapping and interpretation of transcriptomics, we
      developed a method to identify clusters of adjacent and similarly expressed
      genes. Gene expression profiles for 28,945 genes across 101 normal human tissues
      were obtained from the Gene Logic BioExpress system. The expression similarity
      for genes in sliding-windows was measured using average pair-wise Pearson
      correlation coefficients. We identified 187 clusters (p < 10e-4) of co-regulated
      genes, including 2648 genes, or 9.1% of all genes considered and termed these
      "clusters of adjacent and similarly expressed genes" (CASEGs). Genes in 15 (8.2%)
      of these clusters demonstrate a significant co-expression enrichment (p < 10e
      10). This study demonstrates the coordinate expression of neighboring genes and
      provides a comprehensive view of expression-based compartmentalization of the
      human genome, which can be overlaid on genetic susceptibility gene maps.

PMID- 16402894
TI  - Randomized sequence databases for tandem mass spectrometry peptide and protein
      identification.
AB  - Tandem mass spectrometry (MS/MS) combined with database searching is currently
      the most widely used method for high-throughput peptide and protein
      identification. Many different algorithms, scoring criteria, and statistical
      models have been used to identify peptides and proteins in complex biological
      samples, and many studies, including our own, describe the accuracy of these
      identifications, using at best generic terms such as "high confidence." False
      positive identification rates for these criteria can vary substantially with
      changing organisms under study, growth conditions, sequence databases,
      experimental protocols, and instrumentation; therefore, study-specific methods
      are needed to estimate the accuracy (false positive rates) of these peptide and
      protein identifications. We present and evaluate methods for estimating false
      positive identification rates based on searches of randomized databases (reversed
      and reshuffled). We examine the use of separate searches of a forward then a
      randomized database and combined searches of a randomized database appended to a
      forward sequence database. Estimated error rates from randomized database
      searches are first compared against actual error rates from MS/MS runs of known
      protein standards. These methods are then applied to biological samples of the
      model microorganism Shewanella oneidensis strain MR-1. Based on the results
      obtained in this study, we recommend the use of use of combined searches of a
      reshuffled database appended to a forward sequence database as a means providing
      quantitative estimates of false positive identification rates of peptides and
      proteins. This will allow researchers to set criteria and thresholds to achieve a
      desired error rate and provide the scientific community with direct and
      quantifiable measures of peptide and protein identification accuracy as opposed
      to vague assessments such as "high confidence."

PMID- 16402895
TI  - Optimal construction of theoretical spectra for MS/MS spectra identification.
AB  - We derive the optimal number of peaks (defined as the minimum number that
      provides the required efficiency of spectra identification) in the theoretical
      spectra as a function of (i) the experimental accuracy, sigma, of the measured
      ratio m/z; (ii) experimental spectrum density; (iii) size of the database; (iv)
      number of peaks in the theoretical spectra; and (v) types of ions that the peaks
      represent. We show that if theoretical spectra are constructed including b and y
      ions alone, then for sigma = 0.5, which is typical for high-throughput data,
      peptide chains of eight amino acids or longer can be identified based on the
      positions of peaks alone, at a rate of false identification below 1%. To
      discriminate between shorter peptides, additional (e.g., intensity-inferred)
      information is necessary. We derive the dependence of the probability of false
      identification on the number of peaks in the theoretical spectra and on the types
      of ions that the peaks represent. Our results suggest that the class of mass
      spectrum identification problems, for which more elaborate development of
      fragmentation rules (such as intensity model) is required, can be reduced to the
      problems that involve homologous peptides.

PMID- 16402896
TI  - Amino acid propensities revisited.
AB  - Statistical analysis of amino acid patterns in approximately 160,000 alpha
      helices in experimentally determined structures revealed di-, tri-, and
      tetrapeptides, whose frequencies deviate most from the statistical model.
      Importantly, some sequences were never found in alpha- helices. This fact was
      detected initially with tripeptides, where nearly 1% of the possible sequences
      were never seen in the helical segments. For tetrapeptides, this effect is very
      strong and significant; almost 43% of the possible sequences never appear in
      alpha-helices. It is possible that there are some steric and energetic
      restrictions that do not allow these tetrameric amino acid sequences to form
      alpha-helical structure.

PMID- 16402897
TI  - Peroxisome proliferator-activated receptors: how their effects on macrophages can
      lead to the development of a new drug therapy against atherosclerosis.
AB  - Peroxisome proliferator-activated receptors (PPARs) alpha (alpha), beta/delta
      (beta/delta), and gamma (gamma) are members of the nuclear receptor superfamily,
      which also includes the estrogen, androgen, and glucocorticoid receptors. Recent
      evidence suggests that PPARs regulate genes involved in lipid metabolism, glucose
      homeostasis, and inflammation in various tissues; however, the mechanisms
      involved are not completely understood. Anti-diabetic drugs, called glitazones,
      can selectively activate PPARgamma, and hypolipidemic drugs, called fibrates, can
      weakly activate PPARalpha. Both classes of drugs can decrease insulin resistance
      and dyslipidemias, which also makes them attractive for treating the metabolic
      syndrome. The metabolic syndrome exhibits a constellation of risk factors for
      atherosclerosis that include obesity, insulin resistance, dyslipidemias, and
      hypertension. Interestingly, all three PPARs are present in macrophages and can
      therefore have a profound effect on several disease processes, including
      atherosclerosis. Macrophages are key players in atherosclerotic lesion
      development. Currently, the first line of defense in reducing the risk of
      atherosclerosis is aimed at lowering low-density lipoproteins (LDL) and raising
      high-density lipoproteins (HDL), but a large percentage of patients on statins
      still succumb to coronary artery disease. However, with the development of drugs
      selectively activating PPARs, a new arsenal of drugs specifically targeting to
      the macrophage/foam cell may potentially have a profound impact on how we treat
      cardiovascular disease.

PMID- 16402899
TI  - Human flavin-containing monooxygenases.
AB  - This review summarizes recent information concerning the pharmacological and
      toxicological significance of the human flavin-containing monooxygenase (FMO, EC
      1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals
      and drugs and generally converts them into harmless, polar, readily excreted
      metabolites. Sometimes, however, FMO bioactivates chemicals into reactive
      materials that can cause toxicity. Most of the interindividual differences of FMO
      are due to genetic variability and allelic variation, and splicing variants may
      contribute to interindividual and interethnic variability observed for FMO
      mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily
      induced nor readily inhibited, and potential adverse drug-drug interactions are
      minimized for drugs prominently metabolized by FMO. These properties may provide
      advantages in drug design and discovery, and by incorporating FMO detoxication
      pathways into drug candidates, more drug-like materials may be forthcoming.
      Although exhaustive examples are not available, physiological factors can
      influence FMO function, and this may have implications for the clinical
      significance of FMO and a role in human disease.

PMID- 16402900
TI  - Cannabinoid receptors as therapeutic targets.
AB  - CB1 and CB2 cannabinoid receptors are the primary targets of endogenous
      cannabinoids (endocannabinoids). These G protein-coupled receptors play an
      important role in many processes, including metabolic regulation, craving, pain,
      anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged
      directly by agonists or antagonists, or indirectly by manipulating
      endocannabinoid metabolism. In the past several years, it has become apparent
      from preclinical studies that therapies either directly or indirectly influencing
      cannabinoid receptors might be clinically useful. This review considers the
      components of the endocannabinoid system and discusses some of the most promising
      endocannabinoid-based therapies.

PMID- 16402898
TI  - Cytochrome P450 and xenobiotic receptor humanized mice.
AB  - Most xenobiotics that enter the body are subjected to metabolism that functions
      primarily to facilitate their elimination. Metabolism of certain xenobiotics can
      also result in the production of electrophilic derivatives that can cause cell
      toxicity and transformation. Many xenobiotics can also activate receptors that in
      turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and
      xenobiotic transporters. However, there are marked species differences in the way
      mammals respond to xenobiotics, which are due in large part to molecular
      differences in receptors and xenobiotic-metabolizing enzymes. This presents a
      problem in extrapolating data obtained with rodent model systems to humans. There
      are also polymorphisms in xenobiotic-metabolizing enzymes that can impact drug
      therapy and cancer susceptibility. In an effort to generate more reliable in vivo
      systems to study and predict human response to xenobiotics, humanized mice are
      under development.

PMID- 16402901
TI  - Regulation of drug-metabolizing enzymes and transporters in inflammation.
AB  - Inflammation and infection have long been known to downregulate the activity and
      expression of cytochrome P450 (CYP) enzymes involved in hepatic drug clearance.
      This can result in elevated plasma drug levels and increased adverse effects.
      Recent information on regulation of human CYP enzymes is presented, as are new
      developments in our understanding of the mechanisms of regulation. Experiments to
      study the effects of modulating CYP activities on the inflammatory response have
      yielded possible insights into the physiological consequences, if not the
      purpose, of the downregulation. Regulation of hepatic flavin monooxygenases, UDP
      glucuronosyltransferases, sulfotransferases, glutathione S-transferases, as well
      as of hepatic transporters during the inflammatory response, exhibits
      similarities and differences with regulation of CYPs.

PMID- 16402902
TI  - Accessory proteins for G proteins: partners in signaling.
AB  - Accessory proteins involved in signal processing through heterotrimeric G
      proteins are generally defined as proteins distinct from G protein-coupled
      receptor (GPCR), G protein, or classical effectors that regulate the
      strength/efficiency/specificity of signal transfer upon receptor activation or
      position these entities in the right microenvironment, contributing to the
      formation of a functional signal transduction complex. A flurry of recent studies
      have implicated an additional class of accessory proteins for this system that
      provide signal input to heterotrimeric G proteins in the absence of a cell
      surface receptor, serve as alternative binding partners for G protein subunits,
      provide unexpected modes of G protein regulation, and have introduced additional
      functional roles for G proteins. This group of accessory proteins includes the
      recently discovered Activators of G protein Signaling (AGS) proteins identified
      in a functional screen for receptor-independent activators of G protein signaling
      as well as several proteins identified in protein interaction screens and genetic
      screens in model organisms. These accessory proteins may influence GDP
      dissociation and nucleotide exchange at the G(alpha) subunit, alter subunit
      interactions within heterotrimeric G(alphabetagamma) independent of nucleotide
      exchange, or form complexes with G(alpha) or G(betagamma) independent of the
      typical G(alphabetagamma) heterotrimer. AGS and related accessory proteins reveal
      unexpected diversity in G protein subunits as signal transducers within the cell.

PMID- 16402903
TI  - The proteasome and proteasome inhibitors in cancer therapy.
AB  - The proteasome, a multicatalytic proteinase complex, is responsible for the
      majority of intracellular protein degradation. Pharmacologic inhibitors of the
      proteasome possess in vitro and in vivo antitumor activity, and bortezomib, the
      first such agent to undergo clinical testing, has significant efficacy against
      multiple myeloma and non-Hodgkin lymphoma (NHL). Preclinical studies demonstrate
      that proteasome inhibition potentiates the activity of other cancer therapeutics,
      in part by downregulating chemoresistance pathways. Early clinical studies of
      bortezomib-based combinations, showing encouraging activity, support this
      observation. Molecular characterization of resistance to proteasome inhibitors
      has revealed novel therapeutic targets for sensitizing malignancies to these
      agents, such as the heat shock pathway. Below, we review the pharmacologic,
      preclinical, and clinical data that have paved the way for the use of proteasome
      inhibitors for cancer therapy; outline strategies aimed at enhancing the efficacy
      of proteasome inhibitors; and review other potential targets in the ubiquitin
      proteasome pathway for the treatment of cancer.

PMID- 16402904
TI  - Nuclear and mitochondrial compartmentation of oxidative stress and redox
      signaling.
AB  - New methods to measure thiol oxidation show that redox compartmentation functions
      as a mechanism for specificity in redox signaling and oxidative stress. Redox
      Western analysis and redox-sensitive green fluorescent proteins provide means to
      quantify thiol/disulfide redox changes in specific subcellular compartments.
      Analyses using these techniques show that the relative redox states from most
      reducing to most oxidizing are mitochondria > nuclei > cytoplasm > endoplasmic
      reticulum > extracellular space. Mitochondrial thiols are an important target of
      oxidant-induced apoptosis and necrosis and are especially vulnerable to oxidation
      because of the relatively alkaline pH. Maintenance of a relatively reduced
      nuclear redox state is critical for transcription factor binding in
      transcriptional activation in response to oxidative stress. The new methods are
      applicable to a broad range of experimental systems and their use will provide
      improved understanding of the pharmacologic and toxicologic actions of drugs and
      toxicants.

PMID- 16402905
TI  - The regulation and pharmacology of endothelial nitric oxide synthase.
AB  - Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that
      mediates significant and diverse signaling functions in nearly every organ system
      in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key
      source of NO found in the cardiovascular system. This review summarizes the
      pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The
      molecular intricacies of the chemistry of NO and the enzymology of NOSs are
      discussed, followed by a review of the biological activities of NO. This
      information is then used to develop a more global picture of the pharmacological
      control of NO synthesis by NOSs in both physiologic conditions and
      pathophysiologic states.

PMID- 16402906
TI  - Regulation of platelet functions by P2 receptors.
AB  - The main role of blood platelets is to ensure primary hemostasis, which is the
      maintenance of vessel integrity and cessation of bleeding upon injury. While
      playing a major part in acute arterial thrombosis, platelets are also involved in
      inflammation, atherosclerosis, and angiogenesis. ADP and ATP play a crucial role
      in platelet activation, and their receptors are potential targets for
      antithrombotic drugs. The ATP-gated cation channel P2X(1) and the two G protein
      coupled ADP receptors, P2Y(1) and P2Y(12), selectively contribute to platelet
      aggregation and formation of a thrombus. Owing to its central role in the growth
      and stabilization of a thrombus, the P2Y(12) receptor is an established target of
      antithrombotic drugs such as clopidogrel. Studies in P2Y(1) and P2X(1) knockout
      mice and selective P2Y(1) and P2X(1) antagonists have shown that these receptors
      are also attractive targets for new antithrombotic compounds. The potential role
      of platelet P(2) receptors in the involvement of platelets in inflammatory
      processes is also discussed.

PMID- 16402907
TI  - Functional imaging of tumor proteolysis.
AB  - The roles of proteases in cancer are now known to be much broader than simply
      degradation of extracellular matrix during tumor invasion and metastasis.
      Furthermore, proteases from tumor-associated cells (e.g., fibroblasts,
      inflammatory cells, endothelial cells) as well as tumor cells are recognized to
      contribute to pathways critical to neoplastic progression. Although elevated
      expression (transcripts and proteins) of proteases, and in some cases protease
      inhibitors, has been documented in many tumors, techniques to assess functional
      roles for proteases require that we measure protease activity and inhibition of
      that activity rather than levels of proteases, activators, and inhibitors. Novel
      techniques for functional imaging of protease activity, both in vitro and in
      vivo, are being developed as are imaging probes that will allow us to determine
      protease activity and in some cases to discriminate among protease activities.
      These should be useful clinically as surrogate endpoints for therapies that alter
      protease activities.

PMID- 16402908
TI  - Pharmacogenomics of acute leukemia.
AB  - Over the past four decades, treatment of acute leukemia in children has made
      remarkable progress, from this disease being lethal to now achieving cure rates
      of 80% for acute lymphoblastic leukemia and 45% for acute myeloid leukemia. This
      progress is largely owed to the optimization of existing treatment modalities
      rather than the discovery of new agents. However, the annual number of patients
      with leukemia who experience relapse after initial therapy remains greater than
      that of new cases of most childhood cancers. The aim of pharmacogenetics is to
      develop strategies to personalize medications and tailor treatment regimens to
      individual patients, with the goal of enhancing efficacy and safety through
      better understanding of the person's genetic makeup. In this review, we summarize
      recent pharmacogenomic studies related to the treatment of pediatric acute
      leukemia. These include work using candidate-gene approaches, as well as genome
      wide studies using haplotype mapping and gene expression profiling. These
      strategies illustrate the promise of pharmacogenomics to further advance the
      treatment of human cancers, with childhood leukemia serving as a paradigm.

PMID- 16402909
TI  - Regulation of phospholipase C isozymes by ras superfamily GTPases.
AB  - The physiological effects of many extracellular stimuli are mediated by receptor
      promoted activation of phospholipase C (PLC) and consequential activation of
      inositol lipid-signaling pathways. These signaling responses include the
      classically described conversion of PtdIns(4,5)P(2) to the Ca(2+)-mobilizing
      second messenger Ins(1,4,5)P(3) and the protein kinase C-activating second
      messenger diacylglycerol as well as alterations in membrane association or
      activity of many proteins that harbor phosphoinositide binding domains. Here we
      discuss how the family of PLCs elaborates a minimal catalytic core typified by
      PLC-delta to confer multiple modes of regulation on their phospholipase
      activities. Although PLC-dependent signaling is prominently regulated by direct
      interactions with heterotrimeric G proteins or tyrosine kinases, the existence of
      at least 13 divergent PLC isozymes promises a diverse repertoire of regulatory
      mechanisms for this class of important signaling proteins. We focus here on the
      recently realized and extensive regulation of inositol lipid signaling by Ras
      superfamily GTPases directly acting on PLC isozymes and conclude by considering
      the biological and pharmacological ramifications of this regulation.

PMID- 16402910
TI  - Role of ABCG2/BCRP in biology and medicine.
AB  - The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP
      binding cassette (ABC) transporter originally identified by its ability to confer
      drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and
      Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must
      homodimerize to acquire transport activity. ABCG2 is found in a variety of stem
      cells and may protect them from exogenous and endogenous toxins. ABCG2 expression
      is upregulated under low-oxygen conditions, consistent with its high expression
      in tissues exposed to low-oxygen environments. ABCG2 interacts with heme and
      other porphyrins and protects cells and/or tissues from protoporphyrin
      accumulation under hypoxic conditions. Individuals who carry ABCG2 alleles that
      have impaired function may be more susceptible to porphyrin-induced toxicity.
      Abcg2 knock-out models have allowed in vivo studies of Abcg2 function in host and
      cellular defense. In combination with immunohistochemical analyses, these studies
      have revealed how ABCG2 influences the absorption, distribution, and excretion of
      drugs and cytotoxins.

PMID- 16402911
TI  - CO as a cellular signaling molecule.
AB  - Many biological functions of heme oxygenase (HO), such as cytoprotection against
      oxidative stress, vasodilation, neurotransmission in the central or peripheral
      nervous systems, and anti-inflammatory, anti-apoptotic, or anti-proliferative
      potential, have been attributed to its enzymatic byproduct carbon monoxide (CO),
      although roles for biliverdin/bilirubin and iron have also been proposed. In
      addition to these well-characterized effects, recent findings reveal that HO
      derived CO may act as an oxygen sensor and circadian modulator of heme
      biosynthesis. In lymphocytes, CO may participate in regulatory T cell function. A
      number of the known signaling effects of CO depend on stimulation of soluble
      guanylate cyclase and/or activation of mitogen-activated protein kinases (MAPK).
      Furthermore, modulation of caveolin-1 status may serve as an essential component
      of certain aspects of CO action, such as growth control. In this review, we
      summarize recent findings of the beneficial or detrimental effects of endogenous
      CO with an emphasis on the signaling pathways and downstream targets that trigger
      the action of this gas.

PMID- 16402912
TI  - Function of retinoid nuclear receptors: lessons from genetic and pharmacological
      dissections of the retinoic acid signaling pathway during mouse embryogenesis.
AB  - Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular
      differentiation, and tissue homeostasis. The use of in vitro systems initially
      led to the identification of nuclear receptor RXR/RAR heterodimers as possible
      transducers of the RA signal. To unveil the physiological functions of RARs and
      RXRs, genetic and pharmacological studies have been performed in the mouse.
      Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is
      either transcriptionally active or silent are involved in the transduction of the
      RA signal during prenatal development, (b) specific RXRalpha/RAR heterodimers are
      required at many distinct stages during early embryogenesis and organogenesis,
      (c) the physiological role of RA and its receptors cannot be extrapolated from
      teratogenesis studies using retinoids in excess. Additional cell type-restricted
      and temporally controlled somatic mutagenesis is required to determine the
      functions of RARs and RXRs during postnatal life.

PMID- 16402913
TI  - Molecular mechanism of 7TM receptor activation--a global toggle switch model.
AB  - The multitude of chemically highly different agonists for 7TM receptors
      apparently do not share a common binding mode or active site but nevertheless act
      through induction of a common molecular activation mechanism. A global toggle
      switch model is proposed for this activation mechanism to reconcile the
      accumulated biophysical data supporting an outward rigid-body movement of the
      intracellular segments, as well as the recent data derived from activating metal
      ion sites and tethered ligands, which suggests an opposite, inward movement of
      the extracellular segments of the transmembrane helices. According to this model,
      a vertical see-saw movement of TM-VI-and to some degree TM-VII-around a pivot
      corresponding to the highly conserved prolines will occur during receptor
      activation, which may involve the outer segment of TM-V in an as yet unclear
      fashion. Small-molecule agonists can stabilize such a proposed active
      conformation, where the extracellular segments of TM-VI and -VII are bent inward
      toward TM-III, by acting as molecular glue deep in the main ligand-binding pocket
      between the helices, whereas larger agonists, peptides, and proteins can
      stabilize a similar active conformation by acting as Velcro at the extracellular
      ends of the helices and the connecting loops.

PMID- 16402914
TI  - The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest
      derived cells.
AB  - The TLX2 (HOX11L1, Ncx, Enx) and PHOX2B genes encode transcription factors
      crucial in the development of neural-crest-derived cells, leading to ANS
      (autonomic nervous system) specific neuronal lineages. Moreover, they share a
      similar expression pattern and are both involved in downstream steps of BMP (bone
      morphogenetic protein) signalling. In an attempt to reconstruct the gene network
      sustaining the correct development of the ANS, we have undertaken an in vitro
      experimental strategy to identify direct upstream regulators of the TLX2 gene.
      After characterizing a sequence displaying enhancer property in its 5' flanking
      region, we confirmed the functional link between the human PHOX2B and TLX2 genes.
      Transient transfections and electrophoretic-mobility-shift assays suggested that
      PHOX2B is able to bind the cell-specific element in the 5' regulatory region of
      the TLX2 gene, determining its transactivation in neuroblastoma cells. Such
      interaction was also confirmed in vivo by means of chromatin immunoprecipitation
      assay and, in addition, up-regulation of endogenous TLX2 mRNA level was
      demonstrated following PHOX2B over-expression, by quantitative real-time PCR.
      Finally, PHOX2B proteins carrying mutations responsible for CCHS (congenital
      central hypoventilation syndrome) development showed a severe impairment in
      activating TLX2 expression, both in vitro and in vivo. Taken together, these
      results support the PHOX2B-TLX2 promoter interaction, suggesting a physiological
      role in the transcription-factor cascade underlying the differentiation of
      neuronal lineages of the ANS during human embryogenesis.

PMID- 16402915
TI  - Increased systemic inflammation and oxidative stress in patients with worsening
      congestive heart failure: improvement after short-term inotropic support.
AB  - In the present study, we evaluated circulating pro-inflammatory mediators and
      markers of oxidative stress in patients with decompensated CHF (congestive heart
      failure) and assessed whether clinical recompensation by short-term inotropic
      therapy influences these parameters. Patients with worsening CHF (n=29, aged
      61.9+/-2.7 years), NYHA (New York Heart Association) class III-IV, and left
      ventricular ejection fraction of 23.7+/-1.8% were studied. Controls comprised age
      matched healthy volunteers (n=15; 54.1+/-3.2 years). Plasma levels of cytokines
      [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein
      1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE
      selectin (soluble E-selectin)], systemic markers of oxidation [TBARS
      (thiobarbituric acid-reactive substances), 8-isoprostaglandin F(2alpha) and
      nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by
      ELISA and colorimetric assays at admission and 30 days following 72-h milrinone
      (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs
      CRP and oxidative markers were significantly higher in patients on admission
      before inotropic treatment compared with controls (P<0.05). Short-term inotropic
      support improved clinical status as assessed by NYHA classification and by the 6
      min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs
      CRP and markers of oxidation (P<0.05) at 30 days. The effects of milrinone and
      dobutamine were similar. In conclusion, our results demonstrate that patients
      with decompensated CHF have marked systemic inflammation and increased production
      of oxygen free radicals. Short-term inotropic support improves functional status
      and reduces indices of inflammation and oxidative stress in patients with
      decompensated CHF.

PMID- 16402916
TI  - Inefficient coupling between proton transport and ATP synthesis may be the
      pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G
      mutation in mtDNA.
AB  - Mutations in the ATP6 gene of mtDNA (mitochondrial DNA) have been shown to cause
      several different neurological disorders. The product of this gene is ATPase 6,
      an essential component of the F1F0-ATPase. In the present study we show that the
      function of the F1F0-ATPase is impaired in lymphocytes from ten individuals
      harbouring the mtDNA T8993G point mutation associated with NARP (neuropathy,
      ataxia and retinitis pigmentosa) and Leigh syndrome. We show that the impaired
      function of both the ATP synthase and the proton transport activity of the enzyme
      correlates with the amount of the mtDNA that is mutated, ranging from 13-94%. The
      fluorescent dye RH-123 (Rhodamine-123) was used as a probe to determine whether
      or not passive proton flux (i.e. from the intermembrane space to the matrix) is
      affected by the mutation. Under state 3 respiratory conditions, a slight
      difference in RH-123 fluorescence quenching kinetics was observed between mutant
      and control mitochondria that suggests a marginally lower F0 proton flux capacity
      in cells from patients. Moreover, independent of the cellular mutant load the
      specific inhibitor oligomycin induced a marked enhancement of the RH-123
      quenching rate, which is associated with a block in proton conductivity through
      F0 [Linnett and Beechey (1979) Inhibitors of the ATP synthethase system. Methods
      Enzymol. 55, 472-518]. Overall, the results rule out the previously proposed
      proton block as the basis of the pathogenicity of the mtDNA T8993G mutation.
      Since the ATP synthesis rate was decreased by 70% in NARP patients compared with
      controls, we suggest that the T8993G mutation affects the coupling between proton
      translocation through F0 and ATP synthesis on F1. We discuss our findings in view
      of the current knowledge regarding the rotary mechanism of catalysis of the
      enzyme.

PMID- 16402918
TI  - Differential gene and protein expression in abluminal sprouting and intraluminal
      splitting forms of angiogenesis.
AB  - In adult skeletal muscle, abluminal sprouting or longitudinal splitting of
      capillaries can be initiated separately by muscle overload and elevated
      microcirculation shear stress respectively. In the present study, gene and
      protein expression patterns associated with the different forms of angiogenesis
      were examined using a targeted gene array (Superarray), validated by quantitative
      RT (reverse transcription)-PCR and immunoblots. Sprouting angiogenesis induced
      large changes in expression levels in genes associated with extracellular matrix
      remodelling, such as MMP-2 (matrix metalloproteinase-2), TIMP (tissue inhibitor
      of metalloproteinases), SPARC (secreted protein, acidic and rich in cysteine) and
      thrombospondin. Changes in neuropilin, midkine and restin levels, which may
      underpin changes in endothelial morphology, were seen during splitting
      angiogenesis. Up-regulation of VEGF (vascular endothelial growth factor), Flk-1,
      angiopoietin-2 and PECAM-1 (platelet/endothelial cell adhesion molecule-1) was
      seen in both forms of angiogenesis, representing a common angiogenic response of
      endothelial cells. In conclusion, the present study demonstrates that general
      angiogenic signals from growth factors can be influenced by the local
      microenvironment resulting in differing forms of capillary growth to produce a co
      ordinated expansion of the vascular bed.

PMID- 16402917
TI  - Metallothionein isoform 2A expression is inducible and protects against ROS
      mediated cell death in rotenone-treated HeLa cells.
AB  - The role of MT (metallothionein) gene expression was investigated in rotenone
      treated HeLa cells to induce a deficiency of NADH:ubiquinone oxidoreductase
      (complex I). Complex I deficiency leads to a diversity of cellular consequences,
      including production of ROS (reactive oxygen species) and apoptosis. HeLa cells
      were titrated with rotenone, resulting in dose-dependent decrease in complex I
      activity and elevated ROS production at activities lower than 33%. Expression of
      MT2A (MT isoform 2A), but not MT1A or MT1B RNA, was significantly inducible by
      rotenone (up to 7-fold), t-BHP (t-butyl hydroperoxide; 5-fold) and CdCl2 (50
      fold), but not ZnCl2. Myxothiazol treatment did not elevate either ROS or MT2A
      levels, which supports a ROS-related mechanism for rotenone-induced MT2A
      expression. To evaluate the role of MT2A expression, MT2A and MT1B were
      overexpressed in HeLa cells and treated with rotenone. Compared with control and
      MT1B-overexpressing cells, ROS production was significantly lower and cell
      viability higher in MT2A-overexpressing HeLa cells when ROS production was
      enhanced by treatment with t-BHP. Mitochondrial membrane potential was noticeably
      less reduced in both MT-overexpressing cell lines. MT2A overexpression in
      rotenone-treated cells also significantly reduced or delayed apoptosis induction,
      as measured by caspase 3/7 activity and cytosolic nucleosome enrichment. We
      conclude that MT2A offers significant protection against the main death-causing
      consequences of rotenone-induced complex I deficiency in HeLa cells. Our results
      are in support of the protective role against oxidative stress ascribed to MTs
      and provide evidence that MT2A expression may be a beneficial downstream adaptive
      response in complex I-deficient cells.

PMID- 16402919
TI  - Large-scale purification and characterization of non-glycosylated Gc globulin
      (vitamin D-binding protein) from plasma fraction IV.
AB  - Gc globulin, also called vitamin D-binding protein, is a plasma protein involved
      in the extracellular actin-scavenger system. Low levels of Gc globulin have been
      found to correlate with multiple organ failure and nonsurvival of patients with
      fulminant hepatic failure and trauma. Therefore substitution therapy with Gc
      globulin might be beneficial for such patients, increasing their chance of
      survival. In the present study, we describe a large-scale purification process
      for the production of a virus-safe human plasma-derived Gc globulin from Cohn
      fraction IV paste. The process includes three ion-exchange-chromatography steps,
      followed by a gel filtration, and two virus-reduction steps are implemented. The
      Gc globulin product was characterized with respect to purity, functional
      activity, glycosylation and, finally, with respect to content of endotoxin. From
      the results, it can be concluded that human Gc globulin purified from Cohn
      fraction IV is non-glycosylated. The purified Gc globulin is able to mask the
      presence of endotoxin by 20%.

PMID- 16402921
TI  - Two glucose/xylose transporter genes from the yeast Candida intermedia: first
      molecular characterization of a yeast xylose-H+ symporter.
AB  - Candida intermedia PYCC 4715 was previously shown to grow well on xylose and to
      transport this sugar by two different transport systems: high-capacity and low
      affinity facilitated diffusion and a high-affinity xylose-proton symporter, both
      of which accept glucose as a substrate. Here we report the isolation of genes
      encoding both transporters, designated GXF1 (glucose/xylose facilitator 1) and
      GXS1 (glucose/xylose symporter 1) respectively. Although GXF1 was isolated by
      functional complementation of an HXT-null (where Hxt refers to hexose
      transporters) Saccharomyces cerevisiae strain, isolation of the GXS1 cDNA
      required partial purification and micro-sequencing of the transporter, identified
      by its relative abundance in cells grown on low xylose concentrations. Both genes
      were expressed in S. cerevisiae and the kinetic parameters of glucose and xylose
      transport were determined. Gxs1 is the first yeast xylose/glucose-H+ symporter to
      be characterized at the molecular level. Comparison of its amino acid sequence
      with available sequence data revealed the existence of a family of putative
      monosaccharide-H+ symporters encompassing proteins from several yeasts and
      filamentous fungi.

PMID- 16402922
TI  - Congenital adrenal hyperplasia in adults: a review of medical, surgical and
      psychological issues.
AB  - Our knowledge of the experience of adults with congenital adrenal hyperplasia
      (CAH) as they pass through life is only now emerging. In this review we gather
      medical, surgical and psychological literature pertaining to adults with CAH and
      consider this alongside practical experience gained from a dedicated adult CAH
      clinic. There is increasing awareness for the need for multidisciplinary teams
      who have knowledge of CAH particularly with respect to gynaecological surgery and
      clinical psychology for women and testicular function in men. Routine management
      of CAH comprises adjustment of glucocorticoid and mineralocorticoid treatment
      according to individual needs balancing biochemical markers, compliance and long
      term risks. Bone density is one such long term concern and is not greatly reduced
      in most individuals with CAH. More recently, attention has turned to
      cardiovascular risk factors and catecholamine deficiency in adults with CAH.
      Women with CAH require access to an experienced gynaecologist, specialised
      pregnancy care and psychosexual support. The very low fertility rates for women
      with CAH previously reported appear to be improving with time. Men with CAH are
      often lost to follow up and therefore miss out on surveillance for hypogonadism
      either through the effect of adrenal rests of from suppression of gonadotrophins
      resulting in a high prevalence of oligospermia.

PMID- 16402920
TI  - Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac
      sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c).
AB  - We recently documented the expression of a novel human mRNA variant encoding a
      yet uncharacterized SERCA [SR (sarcoplasmic reticulum)/ER (endoplasmic reticulum)
      Ca2+-ATPase] protein, SERCA2c [Gelebart, Martin, Enouf and Papp (2003) Biochem.
      Biophys. Res. Commun. 303, 676-684]. In the present study, we have analysed the
      expression and functional characteristics of SERCA2c relative to SERCA2a and
      SERCA2b isoforms upon their stable heterologous expression in HEK-293 cells
      (human embryonic kidney 293 cells). All SERCA2 proteins induced an increased Ca2+
      content in the ER of intact transfected cells. In microsomes prepared from
      transfected cells, SERCA2c showed a lower apparent affinity for cytosolic Ca2+
      than SERCA2a and a catalytic turnover rate similar to SERCA2b. We further
      demonstrated the expression of the endogenous SERCA2c protein in protein lysates
      isolated from heart left ventricles using a newly generated SERCA2c-specific
      antibody. Relative to the known uniform distribution of SERCA2a and SERCA2b in
      cardiomyocytes of the left ventricle tissue, SERCA2c was only detected in a
      confined area of cardiomyocytes, in close proximity to the sarcolemma. This
      finding led us to explore the expression of the presently known cardiac Ca2+
      ATPase isoforms in heart failure. Comparative expression of SERCAs and PMCAs
      (plasma-membrane Ca2+-ATPases) was performed in four nonfailing hearts and five
      failing hearts displaying mixed cardiomyopathy and idiopathic dilated
      cardiomyopathies. Relative to normal subjects, cardiomyopathic patients express
      more PMCAs than SERCA2 proteins. Interestingly, SERCA2c expression was
      significantly increased (166+/-26%) in one patient. Taken together, these results
      demonstrate the expression of the novel SERCA2c isoform in the heart and may
      point to a still unrecognized role of PMCAs in cardiomyopathies.

PMID- 16402923
TI  - Obstructive sleep apnoea syndrome, plasma adiponectin levels, and insulin
      resistance.
AB  - OBJECTIVE: To investigate whether sleep-disordered breathing and/or plasma
      adiponectin levels are associated with insulin resistance independent of obesity
      or fat distribution in obstructive sleep apnoea syndrome (OSAS). DESIGN: Cross
      sectional clinical study. PATIENTS: Two-hundred and thirteen Japanese patients
      with OSAS aged 27-80 years were divided into three groups: 30 with mild OSAS
      [apnoea-hypopnoea index (AHI) = 10.3 +/- 0.9 episodes/h, minimum oxygen
      saturation (min SpO2) = 87.3 +/- 0.9%], 98 with moderate OSAS (AHI = 28.9 +/- 0.6
      episodes/h, min SpO2 = 82.1 +/- 0.7%), and 85 with severe OSAS (AHI = 68.1 +/-
      2.8 episodes/h, min SpO2 = 72.3 +/- 1.6%). Twenty-one patients undergoing
      diabetic treatments (two mild, nine moderate and 10 severe) were excluded from
      the assessment of insulin resistance and plasma adiponectin measurements.
      MEASUREMENTS: Fat distribution [evaluated according to visceral (V) and
      subcutaneous (S) fat areas using computed tomography scanning at the umbilical
      level], blood pressure, metabolic parameters and hormones including insulin and
      adiponectin were measured. After full polysomnography, venous blood was collected
      between 0600 and 0700 h. RESULTS: Severe OSAS patients were more hypertensive
      than mild and moderate OSAS. Fasting plasma glucose (FPG) and fasting plasma
      insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels
      were all higher in severe OSAS than mild and moderate OSAS patients. HOMA-IR was
      correlated not only with obesity [body mass index (BMI), V and S areas] but also
      with apnoea (AHI, min SpO2 and desaturation time). Additionally, HOMA-IR was
      correlated positively with haemoglobin (Hb)A1c, systolic (SBP) and diastolic
      blood pressure (DBP), triglycerides and free fatty acids (FFA), and negatively
      with high density lipoprotein (HDL)-cholesterol, suggesting that insulin
      resistance is a key component of the metabolic syndrome in OSAS. Plasma
      adiponectin levels were not different between mild, moderate and severe OSAS
      groups. Plasma adiponectin levels were correlated with HOMA-IR and V area, but
      not AHI or min SpO2. Stepwise multiple regression analysis, however, revealed
      that BMI, AHI and plasma adiponectin were independently associated with HOMA-IR.
      CONCLUSION: Sleep-disordered breathing was associated with insulin resistance
      independent of obesity. Although plasma adiponectin was also an independent
      determinant of HOMA-IR in OSAS patients, plasma adiponectin was more closely
      related to obesity than to sleep apnoea. Although treatment of sleep-disordered
      breathing with nasal continuous positive airway pressure reportedly improves
      insulin sensitivity, our findings suggest that treatment of obesity is also
      essential in ameliorating insulin resistance at least through increased plasma
      adiponectin levels in OSAS.

PMID- 16402924
TI  - Breast cyst fluids increase the proliferation of breast cell lines in correlation
      with their hormone and growth factor concentration.
AB  - OBJECTIVE AND DESIGN: Gross cystic disease (GCD) of the breast is reported to
      occur in 7% of women in the developed world and, although not premalignant, is
      thought to be associated with an increased risk of breast cancer. Hormone and
      growth factor concentration levels were measured in breast cyst fluid (BCF) to
      correlate them with their mitogenic activity in tumour (MCF-7) or nontransformed
      (MCF-10A) cells. RESULTS: Oestradiol (E2), oestrone (E1), E2-sulfate (E2-S), E1
      sulfate (E1-S) and epidermal growth factor (EGF) concentrations were, as
      expected, significantly higher in type I than in type II cysts, while
      transforming growth factor-beta 2 (TGF-beta2) showed higher levels in type II
      cysts. Fifty per cent of the BCF samples stimulated [3H]-thymidine incorporation
      into MCF-7 cells while 34.5% inhibited this parameter. In MCF-10A cells, most BCF
      samples were stimulatory (85%). E2, E1 and EGF concentrations in BCF samples
      correlated significantly and positively with cell proliferation in MCF-7 cells,
      whereas a significant negative correlation was found for TGF-beta2. In MCF-10A
      cells, only E2-S and E1-S exhibited significant positive correlation, whereas a
      significant negative correlation was found for TGF-beta2. Progesterone (Pg), E2
      and EGF incubated under the same conditions had a stimulatory effect on [3H]
      thymidine incorporation into MCF-7 cells, whereas TGF-beta2 inhibited this
      parameter. Pg, E2, E1 and EGF significantly stimulated this parameter in MCF-10A
      cells. CONCLUSIONS: The stimulatory action of BCF on cell proliferation in a
      model of human breast epithelial cells could partly explain the increased
      incidence of breast cancer in cyst-bearing women.

PMID- 16402925
TI  - Expression of ACTH receptor pathway genes in glucose-dependent insulinotrophic
      peptide (GIP)-dependent Cushing's syndrome.
AB  - OBJECTIVE: The molecular mechanisms responsible for glucose-dependent
      insulinotrophic peptide receptor or gastric inhibitory polypeptide receptor
      (GIPR) ectopic expression and function in GIP-dependent Cushing's syndrome (CS)
      are still unknown. GIPR presumably acts, like the ACTH receptor (ACTHR), through
      the Gs protein/cyclic AMP/protein kinase A (PKA) pathway to stimulate
      steroidogenesis. We studied the expression of several genes involved in this
      pathway in the adrenal tissues of patients with GIP-dependent CS. DESIGN AND
      METHODS: RNA was extracted from adrenal tissues from nine patients with GIP
      dependent CS [seven ACTH-independent bilateral macronodular adrenal hyperplasia
      (AIMAH), two adenomas], two control whole adult adrenals, two fasciculata cell
      enriched preparations from normal adrenals, seven patients with Cushing's disease
      (CD) and two normal pancreas. Multiplex reverse transcriptase polymerase chain
      reaction (RT-PCR) evaluated the expression of GIPR, ACTHR, SF-1, Nur77, DAX-1,
      CYP11A, 3beta-HSD, CYP21, CREB and CREM genes. RESULTS: GIPR mRNA was
      overexpressed in all GIP-dependent cases. In normal adrenals and in the adrenal
      tissues from patients with CD, minimal amounts of GIPR mRNA were detected. ACTHR
      mRNA expression was observed in all GIP-dependent adrenal tissues. The expression
      of steroidogenic enzymes and some specific and ubiquitous transcription factors
      (TFs) involved in the ACTHR cascade was significantly reduced. CONCLUSIONS: Our
      results indicate that the expression of ACTHR and other genes located downstream
      in the ACTHR cascade, including steroidogenic enzymes genes and some
      transcription factors, are relatively suppressed in GIP-dependent CS. Although
      the expression of aberrant receptors plays an important role in steroidogenesis
      and initiation of cell proliferation, additional genetic events might occur,
      altering the activity of the ACTHR pathway.

PMID- 16402926
TI  - Comprehensive study of urinary cortisol metabolites in hyperthyroid and
      hypothyroid patients.
AB  - OBJECTIVE: To further analyse the significance and mutual relationship of thyroid
      function-linked alterations in cortisol metabolism that have been separately and
      variously reported. PATIENTS AND MEASUREMENTS: Twenty-four-hour urine samples
      from 21 patients with hyperthyroidism (Graves' disease), 16 patients with
      hypothyroidism (Hashimoto's thyroiditis), 21 healthy age- and sex-matched
      controls for hyperthyroidism, and 16 healthy age- and sex-matched controls for
      hypothyroidism were evaluated for 6beta-hydroxycortisol (6beta-OHF),
      tetrahydrocortisol (THF), tetrahydrocortisone (THE), allo-tetrahydrocortisol
      (allo-THF), urinary free cortisol (UFF), urinary free cortisone (UFE) and 17
      hydroxycorticosteroid (17-OHCS). RESULTS: Urinary 17-OHCS, THE and allo-THF
      levels increased considerably in hyperthyroid patients compared to the controls,
      while UFF and THF showed no difference between the two groups. Urinary 6beta-OHF
      was significantly lower in the hyperthyroid patients than in the controls. Both
      the urinary allo-THF + THF/THE and the UFF/UFE ratios were significantly lower in
      the hyperthyroid patients than in the controls, whereas only the former was
      significantly higher in the hypothyroid patients than in the controls. The
      urinary allo-THF/THF ratio was significantly higher in the hyperthyroid patients
      and significantly lower in the hypothyroid patients than in the controls. In an
      analysis of pooled subjects including all groups (n = 64), free T4 levels
      correlated negatively (P < 0.0001) with the urinary allo-THF + THF/THE ratio but
      not with the UFF/UFE ratio. The serum levels of free T4 correlated positively (P
      < 0.0001) with the urinary allo-THF/THF ratio. CONCLUSION: The thyroid hormones
      seem to affect the total 11beta-HSD activity (allo-THF + THF/THE) more strongly
      than the renal 11beta-HSD2 activity (UFF/UFE). 5alpha-reductase activity (allo
      THF/THF) is also enhanced in hyperthyroidism, while the reduction of urinary
      6beta-OHF in hyperthyroidism might be a secondary effect of the altered activity
      of the total 11beta-HSD and 5alpha-reductase.

PMID- 16402927
TI  - Hyperglycaemia acutely decreases circulating dehydroepiandrosterone levels in
      healthy men.
AB  - OBJECTIVE: This study was conducted in order to evaluate the effect of glucose
      insulin homeostasis on adrenal steroids and was designed to separate the effects
      of hyperglycaemia from those of insulin. DESIGN: Eight healthy men aged 22.6 +/-
      3.4 (SD) underwent an 80 mU/m2/min hyperinsulinaemic euglycaemic 100-min clamp, a
      200-min graded glucose infusion at 2-16 mg/kg/min and a measurement of fat mass.
      MEASUREMENTS: Circulating glucose, insulin and adrenal steroid levels including
      dehydroepiandrosterone (DHEA) were determined before and during both infusion
      tests. Steroid variations in relation to insulinaemia and glycaemia were analysed
      using univariate, multivariate tests and nonlinear mixed models. RESULTS:
      Hyperinsulinaemia induced no significant modification of adrenal steroid levels.
      By contrast, hyperglycaemia decreased all adrenal steroids except DHEA-sulphate
      by 47-66%. The drop occurred early, averaging 51% for 17OH pregnenolone and 57%
      for DHEA at the 80th minute of glucose infusion, whereas blood glucose was 7.1 +/
      1.2 mmol/1. This effect was independent of insulinaemia, fat mass and waist
      circumference. Thus, we estimated models that could best predict steroid
      variations according to blood glucose. At thresholds defining impaired fasting
      glycaemia and diabetes, the estimated decrease in DHEA was 40% and 45%,
      respectively, culminating at 60% at 9.3 mmol/1 glycaemia, with no detectable
      further decrease. CONCLUSIONS: Our data suggest that hyperglycaemia dramatically
      decreases adrenal androgen levels in men, possibly by acting at early steps of
      synthesis, independently of insulinaemia and fat mass.

PMID- 16402928
TI  - Influence of gender and pubertal stage at diagnosis on growth outcome in
      childhood thyrotoxicosis: results of a collaborative study.
AB  - OBJECTIVE: To evaluate the influence of sex as well as pubertal stage at
      diagnosis on the growth outcome of childhood thyrotoxicosis. DESIGN:
      Retrospective, collaborative study. PATIENTS AND METHODS: Longitudinal
      auxological evaluation in 101 patients (M/F 23/78) for 4.7 +/- 3.1 years
      subdivided according to pubertal stage at diagnosis into prepubertal (group I)
      and pubertal (group II). RESULTS: At diagnosis height and bone age (BA) standard
      deviation score (SDS) were positive both in girls and boys of groups I and II. In
      boys of group II, height SDS was significantly higher than in girls of the same
      group (P = 0.007) and in boys of group I (P = 0.026). During the follow-up, in
      group I, height SDS remained positive without significant differences between
      boys and girls, and in group II, height SDS remained significantly lower in girls
      than in boys. The age at onset of puberty and the age at menarche were within the
      normal range. Final height (FH) was within target height (TH) range in all groups
      The FH SDS and the height gain (FH-TH) were similar in girls and in boys in group
      I and significantly higher in boys than in girls (P < 0.05) in group II. The boys
      of group II showed a mean height gain significantly greater than that found in
      all the other groups. CONCLUSIONS: Despite the advancement of BA at presentation,
      there were no adverse effects on subsequent growth and FH; the growth outcome
      seems to be better in boys than in girls in group II.

PMID- 16402929
TI  - Increase of bioavailable testosterone is associated with gain in bone mineral
      density after cure of primary hyperparathyroidism in postmenopausal women.
AB  - OBJECTIVE: The recovery of bone mineral density (BMD) after surgical cure of
      primary hyperparathyroidism (PHPT) seems to be multifactorial and not just
      dependent on declining PTH. The aim of the present study was to evaluate the role
      of sex steroids in this context. DESIGN AND PATIENTS: Thirty-six postmenopausal
      women with PHPT were examined before and 1 year after curative parathyroidectomy.
      Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83).
      BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry.
      No patient received any replacement therapy with sex hormones or treatment with
      corticosteroids, oestrogen receptor modulators or bisphosphonates. MEASUREMENTS:
      Serum concentrations of oestradiol, testosterone, androstenedione,
      dehydroepiandrosterone sulphate, SHBG, PTH and calcium. RESULTS: Postoperative
      increase of free (bioavailable) testosterone was positively correlated to the
      change of BMD in the hip (P < 0.01), whereas the change of PTH in serum
      correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple
      regression analysis showed that bioavailable testosterone was the most important
      determinant of change in BMD in both spine and hip (femoral neck: P < 0.05;
      Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The
      increase of bioavailable testosterone after curative parathyroidectomy was
      related to declining SHBG. CONCLUSIONS: An increase of bioavailable testosterone
      following surgical cure of PHPT is related to improvement of hip and lumbar spine
      BMD in postmenopausal women. This previously unknown hormonal interaction may
      also be important to other aspects of hyperparathyroidism.

PMID- 16402930
TI  - Clinical utility of telomerase for the diagnosis of malignant well-differentiated
      endocrine tumours.
AB  - OBJECTIVE: The distinction between benign and malignant well-differentiated
      endocrine tumours is hard to achieve. The aim of the present study was to
      determine whether detection of telomerase or quantification of human telomerase
      reverse transcriptase protein subunit (hTERT) differ between benign and malignant
      endocrine tumours. PATIENTS AND METHODS: This retrospective study investigated 31
      well-differentiated primary endocrine tumours. Based on clinical and
      histopathological criteria, tumours were categorized with the most recent WHO
      classification as 'benign' (n = 14), 'uncertain' (n = 5) or 'malignant' (n = 12)
      with (n = 7) or without (n = 5) metastasis after a mean follow-up of 40.4 +/-
      25.8 months (4-122 months). All these tumours were assayed for telomerase
      activity and hTERT mRNA expression [real-time quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR)]. RESULTS: Telomerase activity was detected in
      7 malignant and metastatic tumours, in 1 malignant tumour without metastases, in
      1 uncertain tumour and in 1 benign tumour. hTERT mRNA levels were significantly
      higher in malignant endocrine tumours with or without metastases (P = 0.001) when
      compared to benign tumours. The negative predictive value of hTERT mRNA
      quantification for the diagnosis of malignancy was 88.9%, whereas the positive
      predictive value was 68.7%. CONCLUSION: The presence of telomerase activity
      within the primary endocrine tumour might indicate a malignant tumour and might
      suggest the need for an attentive search for concomitant metastases.
      Quantification of hTERT mRNA could be used in clinical practice to exclude
      malignancy in most endocrine tumours.

PMID- 16402931
TI  - Serum ghrelin concentrations in patients with chronic renal failure undergoing
      dialysis.
AB  - BACKGROUND: Ghrelin is a recently discovered protein hormone mainly synthesized
      in the gastric endocrine cells. This hormone not only is a potent growth hormone
      secretagogue but also is involved in the regulation of food ingestion and energy
      metabolism. Derangements in ghrelin secretion in patients with chronic renal
      failure (CRF) have not been fully evaluated. OBJECTIVE: Our aim has been to
      quantify serum concentrations of total ghrelin in a group of patients with CRF on
      chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in
      comparison with a group of patients on conservative management (predialysis).
      PATIENTS AND MEASUREMENTS: We studied 68 CRF patients treated by HD (n = 30, 16
      men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7
      years). A group of 19 uraemic patients on conservative management served as the
      control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were
      measured in all subjects. RESULTS: Patients undergoing HD showed similar
      concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs
      9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin
      concentrations significantly lower than those found in patients on conservative
      management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum
      ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD
      patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus
      did not influence ghrelin levels. Serum GH levels were positively correlated with
      serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P
      < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and
      IGF I were found. CONCLUSIONS: These results suggest that PD is accompanied by a
      striking decrement in baseline ghrelin concentrations in comparison with values
      found both in HD and control patients. Further studies are necessary to determine
      mechanisms involved in ghrelin regulation in uraemic patients.

PMID- 16402932
TI  - Identification of wild type and variants of oestrogen receptors in
      polymorphonuclear and mononuclear leucocytes.
AB  - OBJECTIVE: Leucocytes play an important role in the pathogenesis of autoimmune
      and cardiovascular diseases. Clinical and epidemiological observations indicate
      that the sex steroid hormones, particularly oestrogens, may regulate leucocyte
      functions. The assumption that oestrogens have a direct effect on leucocytes has
      to be supported by identification of functional oestrogen receptors (ER) in
      leucocytes. This study aimed at investigating the presence of ER subtypes in
      different types of leucocytes isolated from peripheral blood of female and male
      donors. DESIGN AND PATIENTS: A total of nine men (age range 18-43 years) and nine
      women (age range 19-42 years) all healthy blood donors, were recruited for the
      study. The donors did not receive any medication or hormonal contraceptives for
      the last three months. Ten millilitres of peripheral blood was collected from
      each donor. Polymorphonuclear leucocytes (PMN) and peripheral blood mononuclear
      cells (PBMC) were purified by density gradient centrifugation. MEASUREMENTS:
      ERalpha and ERbeta mRNA expression was measured by real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR), and ER proteins were analysed
      by Western blot in the PBMC and PMN leucocyte populations. In addition,
      expression profiles of ER variant isoforms were characterized by conventional PCR
      using the splice-targeted primer approach. RESULTS: Although we detected wild
      type ERalpha and ERbeta mRNAs in PBMC but not in PMN cells, the ERalpha and
      ERbeta proteins were found in both cell types using Western blot. We observed
      that both ERalpha and ERbeta proteins differ in size between PMN and PBMC,
      suggesting that the two leucocyte populations contain diverse variant isoforms of
      ERalpha and ERbeta. RT-PCR analysis of exon-deleted ER splice variants revealed
      that PBMC express several exon-deleted variants of ERalpha and ERbeta, along with
      wild-type receptor, whereas the PMN cells only express exon-deleted variant
      isoforms and no wild-type ERalpha or ERbeta. CONCLUSIONS: Our study demonstrates
      the presence of ERalpha and ERbeta in PBMC and PMN cells from female and male
      donors. The ERalpha and ERbeta genes have complex transcriptional profiles, with
      many receptor variant isoforms being expressed. Considering the diversity of ER
      isoforms in leucocyte subtypes, we conclude that the expected effect of oestrogen
      would be highly cell type-specific. Further studies are needed to test the
      functional activity of ER isoforms and their relation to disease.

PMID- 16402933
TI  - Assessing the HPA axis in patients with pituitary disease: a UK survey.
AB  - OBJECTIVE: Assessing the integrity of the hypothalamic-pituitary-adrenal (HPA)
      axis following pituitary surgery is necessary to determine the requirement for
      glucocorticoid replacement therapy, but there remains controversy about the
      optimum way to measure this. DESIGN AND MEASUREMENTS: Postal questionnaire survey
      among UK endocrinologists to evaluate the current methods used. RESULTS: The
      response rate was low (81 out of 598 questionnaires mailed), although 85% were
      consultants. Fifty-five percent measured 9:00 h plasma cortisol in the immediate
      postoperative phase. Most carried out definitive testing between 4 and 12 weeks:
      36% routinely used the insulin tolerance test (ITT), 59% used the short synacthen
      test (SST). The 30-min cortisol value was used by 67% as a 'pass' when
      interpreting the results. Others included cortisol measurement at 60 min (17%) or
      incremental value (7%). For long-term follow-up of patients not rendered ACTH
      deficient by surgery, 64% used the SST for patients who had received
      radiotherapy. If patients had not had radiotherapy, 42% used the SST, whereas 33%
      did no routine testing unless the patient was symptomatic or there was evidence
      of tumour recurrence on imaging. If patients were symptomless but 'failed' the
      chosen test, 28% still treated the patient with glucocorticoid replacement, 38%
      retested before treatment and 24% recommended glucocorticoid cover for when
      unwell or 'stressed'. Fifty-six percent used hydrocortisone at doses of 20 mg/day
      as replacement therapy. CONCLUSION: Thus, assessment of the HPA axis remains
      controversial. Although the SST is becoming more popular, there is still
      considerable variation in the interpretation of results and, in particular, the
      decision of whether or not to treat with lifelong glucocorticoid replacement
      therapy.

PMID- 16402934
TI  - Low normal TSH levels are associated with low bone mineral density in healthy
      postmenopausal women.
AB  - OBJECTIVE: Hyperthyroidism is accompanied by low bone mass. Because the reference
      range of TSH levels is defined statistically, some individuals with low normal
      TSH levels may have mild hyperthyroidism and reduced bone mass. We therefore
      determined whether serum TSH levels correlate with bone mineral density (BMD).
      DESIGN: A cross-sectional hospital-based survey. Participants Nine hundred and
      fifty-nine healthy postmenopausal women. MEASUREMENTS: We measured BMD at the
      lumbar spine and femoral neck using dual energy X-ray absorptiometry, and serum
      TSH concentrations using immunoluminometry. RESULTS: BMD at the lumbar spine and
      femoral neck increased with TSH level (P for trend < 0.001 at both sites). Even
      after adjustment for age, years since menopause and body mass index, subjects
      with low normal TSH levels (0.5-1.1 mU/l) had significantly lower BMDs at the
      lumbar spine (0.863 +/- 0.009 g/cm2 vs 0.900 +/- 0.009 g/cm2, P = 0.004) and
      femoral neck (0.660 +/- 0.006 g/cm2 vs 0.683 +/- 0.006 g/cm2, P = 0.006) than
      those with high normal TSH levels (2.8-5.0 mU/l), as well as a 2.2-fold increased
      risk of osteoporosis (95% confidence interval: 1.2-4.0). CONCLUSION: These
      results suggest that low normal TSH levels may not be physiological for
      postmenopausal women and, during treatment of hypothyroidism, may not be adequate
      for avoiding osteoporosis.

PMID- 16402935
TI  - Does the prevalence of gsp mutations in GH-secreting pituitary adenomas differ
      geographically or racially? Prevalence of gsp mutations in Japanese patients
      revisited.
AB  - OBJECTIVE: The prevalence of gsp mutations in GH-secreting pituitary adenomas was
      thought to differ geographically or racially, given its exceptionally lower
      incidence among Japanese patients (4.4-9.3%) compared to other regions (30-50%).
      However, this notion is now being challenged after a recent paper reported a
      53.3% incidence among Japanese with acromegaly. We have since re-evaluated the
      prevalence of gsp mutations on a larger scale. PATIENTS: One hundred Japanese
      acromegaly patients with surgically confirmed GH-secreting pituitary adenomas
      were enrolled. METHODS: mRNAs from primary cultured adenomas were used for
      reverse transcriptase-polymerase chain reaction and direct sequencing of the
      Gsalpha subunit. Patient data were reviewed from medical charts. RESULTS: There
      were 53 gsp mutations (53%), consisting of 42 Arg201Cys, one Arg201His, one
      Arg201Ser, 8 Gln227Leu, and one Gln227Arg mutation. Age at operation, sex ratio,
      basal serum GH and IGF-I levels were no different with or without the mutations.
      In contrast, patients responded differently to most dynamic tests with
      statistical significance: serum GH levels in gsp-positive patients had blunted
      response to GHRH, were well suppressed by bromocriptine, and had higher rates of
      paradoxical response to TRH. Notably, paradoxical response to LHRH was observed
      exclusively in gsp-negative patients. Octreotide suppressed GH levels strongly
      regardless of gsp status. These clinical characteristics are similar to those of
      Caucasian patients. CONCLUSION: We conclude that the prevalence of gsp mutations
      in Japanese acromegaly patients is comparable to those of other reports from
      various regions. Therefore, Japanese patients do not stand as an example for
      geographical or racial difference in the prevalence of gsp mutations in GH
      secreting pituitary adenomas.

PMID- 16402936
TI  - Investigations of thyroid hormones and antibodies based on a community health
      survey: the Busselton thyroid study.
AB  - OBJECTIVE: Overt or subclinical thyroid dysfunction is common within the
      community, yet the significance of subtle anomalies in thyroid function tests
      remains contentious. The aims of this study were to: (a) establish reference
      intervals for serum-free thyroxine (FT4), thyroid-stimulating hormone (TSH) and
      thyroid antibodies (antithyroperoxidase, TPOAb and antithyroglobulin, TgAb) in
      the Busselton community of south-western Western Australia; and (b) determine the
      prevalence of thyroid hormone anomalies in this community. SUBJECTS AND DESIGN:
      In 1981, 2115 adults residing in Busselton participated in a cross-sectional
      health survey that involved blood collection and a questionnaire on lifestyle and
      general health history. MEASUREMENTS: Serum samples were analysed for FT4, TSH,
      TPOAb and TgAb by immunochemiluminescent assays. RESULTS: Based on standard
      statistical approaches and using guidelines recommended by the National Academy
      of Clinical Biochemistry (NACB), reference intervals were derived for each
      analyte: 9-23 pmol/l for FT4, 0.4-4.0 mIU/l (TSH), < 35 KIU/l (TPOAb) and < 55
      KIU/l (TgAb). The prevalence of elevated thyroid antibodies was 12.4% among
      subjects without a history of thyroid disease and is more common in women than in
      men. Elevated thyroid antibody levels were observed at both extremes of TSH
      abnormality, but were more commonly increased when TSH levels were above 4.0
      mIU/l (63% subjects) than for those with TSH levels 0.4-4.0 mIU/l (7.8%
      subjects). CONCLUSIONS: This study establishes the prevalence of antibodies to
      thyroperoxidase and thyroglobulin in a community-based sample and reference
      intervals for free T4 and TSH. When the NACB decision limits are applied to older
      men or women, there is a markedly increased number with 'elevated' autoantibody
      levels compared to sex- and age-specific reference intervals.

PMID- 16402937
TI  - Genotyping of an Italian papillary thyroid carcinoma cohort revealed high
      prevalence of BRAF mutations, absence of RAS mutations and allowed the detection
      of a new mutation of BRAF oncoprotein (BRAF(V599lns)).
AB  - OBJECTIVES: The genes RET and RAS, and more recently BRAF, have been shown to be
      frequently mutated in human papillary thyroid carcinomas (PTC). The aim of this
      study was to genotype for these mutations a cohort of thyroid tumours collected
      at our institutions. DESIGN AND PATIENTS: Thyroid tumours removed from 51
      subjects were analysed, including 43 PTC and 8 non-PTC tumours [3 follicular
      adenomas (FA), 4 follicular carcinomas (FTC) and 1 anaplastic carcinoma (AC)].
      MEASUREMENTS: RET/PTC1 and RET/PTC3 expression was evaluated by reverse
      transcriptase-polymerase chain reaction, whereas screening of BRAF (exon 15) and
      RAS (HRAS, KRAS2 and NRAS) mutations were performed, respectively, by single
      strand conformation polymorphism and denaturing high-pressure liquid
      chromatography. RESULTS: RET/PTC expressions was positive in 5/43 (11.6%) PTC and
      in none of the non-PTC tumour. Similarly, BRAF mutations were positive only in
      PTC, but with a higher prevalence (24/43 positives, 55.8%). All but one BRAF
      mutation resulted in the prototypic substitution of valine 600 with a glutamic
      acid. In one case, a somatic in-frame insertion of three bases at codon 599
      resulted in the insertion of an additional valine. RET/PTC expression and BRAF
      mutations were mutually exclusive. Screening of the RAS gene allowed
      identification of oncogenic mutations in 1/3 (33.3%) FA and 3/4 (75%) FTC. None
      of the PTCs was positive for RAS. CONCLUSIONS: These data indicate that BRAF
      mutations are the most frequent genetic event in PTC and that RAS mutations,
      besides being a genetic hallmark of follicular tumours, are rare or completely
      absent in PTC from our area. Together, BRAF mutations and rarer RET
      rearrangements accounted for a genetic event in two-thirds of PTCs. This study
      showed a novel and presumably oncogenic mutation of BRAF, which is BRAF(V599Ins).

PMID- 16402938
TI  - Rapidly progressing high o,p'DDD doses shorten the time required to reach the
      therapeutic threshold with an acceptable tolerance: preliminary results.
AB  - INTRODUCTION: It has been reported that the therapeutic threshold of mitotane,
      plasma level above 14 microg/ml, is achieved within 3-5 months after o,p'DDD
      treatment initiation in patients with adrenocortical carcinoma (ACC). OBJECTIVE
      AND DESIGN: We evaluated pharmacokinetic and tolerance of a high-dose schedule of
      pure o,p'DDD treatment given in 500-mg tablets of mitotane (Lysodren, Bristol
      Myers Squibb, HRA Pharma, Paris, France) in four patients with ACC and two
      patients with Cushing's syndrome-related endocrine tumours. It was administered
      at a starting dosage of 3 g/day, which was rapidly increased to 6-9 g/day within
      2 weeks according to digestive tolerance and then adjusted according to tolerance
      and plasma o,p'DDD monitoring. Patients were followed up until they reached the
      therapeutic threshold of mitotane, and toxicity was recorded. A relationship
      between o,p'DDD dose and plasma level was sought. RESULTS: The highest starting
      dosage given ranged between 6 and 9 g a day, during the first two weeks. The
      daily maintenance dose ranged 4.5-9 g during the next 2 weeks and 3-9 g by the
      second month of treatment. The therapeutic threshold was reached in all four
      patients who received o,p'DDD treatment for at least 1 month. Among these four
      patients, the toxic threshold (plasma mitotane level > 20 microg/ml) was even
      reached at 6 weeks of therapy in three patients. Grade 1, 2 or 3 toxicity was
      observed in 3, 2 and 1 patients, respectively. Toxicity resolved after reduction
      or discontinuation of o,p'DDD therapy. A significant linear correlation was found
      between plasma mitotane dose and plasma level. CONCLUSIONS: These results suggest
      that a high-dose o,p'DDD therapeutic schedule is feasible with an acceptable
      toxicity and may shorten the time required to reach the therapeutic schedule from
      3-5 months to 4 weeks. These patients require a close follow-up, combining
      clinical and plasma o,p'DDD level monitoring every second week. A confirmatory
      study is ongoing.

PMID- 16402939
TI  - A century of corneal transplantation.

PMID- 16402942
TI  - Gillies Lecture: comparative anatomy of V esotropia.

PMID- 16402943
TI  - Why is the moon white?
AB  - Land's Retinex theory is used to explain why we perceive the colour of the moon
      as white. The lightness values of coloured areas are computed and the energy at
      the particular area (moon) is compared with the surrounding area (space-vacuum).

PMID- 16402944
TI  - Constancy, illumination and the whiteness of the moon.

PMID- 16402945
TI  - Confusing the moon's whiteness with its brightness.

PMID- 16402946
TI  - The dark shade of the moon.

PMID- 16402947
TI  - Protecting the retinal pigment epithelium during macular hole surgery.
AB  - Herein a new surgical technique used during pars plana vitrectomy with internal
      limiting membrane peeling for macular hole surgery is reported. Perfluorocarbon
      liquid is used to tamponade the macular hole in order to prevent indocyanine
      green contact with the retinal pigment epithelium.

PMID- 16402948
TI  - Visual experience during phacoemulsification under topical anaesthesia: a
      nationwide survey of Singapore ophthalmologists.
AB  - BACKGROUND: All patients undergoing phacoemulsification under topical anaesthesia
      experience a variety of visual sensations that may be frightening in a small
      proportion of patients. This study evaluates Singapore ophthalmologists'
      knowledge and practices regarding patients' visual experience during
      phacoemulsification under topical anaesthesia. METHODS: A nationwide survey of
      all ophthalmologists in Singapore who had performed at least one cataract surgery
      within the last year was carried out. Questions regarding patients' experience
      were asked. Surgeons were also asked about patients' fear during surgery,
      usefulness of preoperative counselling and feedback from patients
      postoperatively. RESULTS: Of 105 ophthalmologists 89 responded, of which 44
      performed phacoemulsification under topical anaesthesia. The percentage of
      respondents who thought that the patients experienced the various visual
      sensations were: no light perception (4.6%), light perception (97.7%), one or
      more colours (95.5%), flashes of light (77.3%), movements (90.9%), instruments
      (61.4%), surgeon's hands/fingers (56.8%), surgeon (47.7%) and change in
      brightness of light (90.9%). Although 52.3% of surgeons believed that patients
      may be frightened by their visual experience and 50.0% felt that preoperative
      counselling would be useful in reducing such fear, only 11.4% routinely offered
      preoperative counselling and 18.2% counselled their patients occasionally. In
      total, 50.0% ophthalmologists had patients who reported to them that they could
      see during surgery, whereas 20.5% had been told by patients that they were
      frightened by the visual experience. CONCLUSION: Despite the awareness of
      patients' visual experience and the belief that preoperative counselling may be
      useful, most ophthalmologists do not counsel their patients preoperatively.

PMID- 16402949
TI  - Cicatricial entropion and trichiasis in an urban Australian population.
AB  - BACKGROUND: Cicatricial entropion and trichiasis may be caused by a variety of
      diseases, of which trachomatous entropion is the commonest worldwide. The
      spectrum of disease in the authors' community is quite different. The purpose of
      this study was to establish the aetiology of entropion and trichiasis in patients
      referred to a Melbourne-based subspecialty oculoplastics practice, excluding
      epiblepharon, congenital entropion and involutional entropion, and to compare the
      final diagnosis with the referring diagnosis. METHODS: All records of patients
      with cicatricial entropion and trichiasis presenting to the practice of one of
      the authors over the period 1990-2000 were analysed. Demographic data, referring
      diagnosis and final diagnosis were tabulated. RESULTS: The commonest final
      diagnosis was ocular cicatricial pemphigoid. In only a small proportion of cases
      was this diagnosis considered by the referring practitioners. In addition, two
      cases of undiagnosed conjunctival neoplasia presented with entropion and
      trichiasis. CONCLUSION: In all patients with entropion and trichiasis, a careful
      history and examination should be obtained and appropriate investigations
      performed to try and establish a firm diagnosis.

PMID- 16402950
TI  - Daytime presentations to a metropolitan ophthalmic emergency department.
AB  - BACKGROUND: To determine the diagnoses causing patients to present to a dedicated
      ophthalmic emergency department. To detect associations with patient
      demographics. METHODS: A retrospective review of all presentations to the Sydney
      Eye Hospital Emergency Department between 08:00 and 17:00 hours from 1 January to
      31 December 2001 was conducted. Data were analysed for frequency of diagnoses and
      patient demographics. RESULTS: A total of 10 599 patients presented to the
      emergency department on 16 870 occasions. On average, 46 patients were seen
      daily. Men accounted for 57.7% and women for 42.3% of presentations. The five
      commonest reasons for presentation were conjunctivitis, keratitis, cataract,
      corneal abrasion and iridocyclitis. CONCLUSIONS: Ocular surface and anterior
      segment diagnoses are predominant among emergency presentations. Statistically
      significant associations exist between sex and selected diagnoses, and between
      age and almost all of the commonest diagnoses. The emergency department functions
      as a primary care provider with most patients discharged following initial
      consultation.

PMID- 16402951
TI  - Implementation and evaluation of an ophthalmic nurse practitioner emergency eye
      clinic.
AB  - BACKGROUND: To describe the implementation and assess the efficacy of an
      ophthalmic nurse practitioner (ONP) emergency eye clinic. METHODS: In a 13-month
      period, patients were assessed in an ONP emergency eye clinic in a teaching
      hospital setting. The ONP clinic was run on a defined scope of practice. Risk
      assessment was carried out in two audit sessions, 4 weeks duration each, at
      months 1 and 7. Patient outcomes were monitored for reattendance to the
      department following discharge. RESULTS: A total of 259 patients were assessed,
      143 (55.2%) were within the scope of practice. In the two audit periods,
      concordance with the ophthalmologist was high, diagnosis 100% and management
      95.2%. Many patients assessed (111, 42.9% of total) had minor external eye
      conditions--chiefly corneal foreign body or abrasion (n = 50), conjunctivitis (n
      = 14) and minor (non-alkali) chemical injuries (n = 11). No reattendance was
      noted in these patients when monitored for a mean of 12 months (range 7-19
      months). CONCLUSIONS: This study demonstrates the safety and effectiveness of an
      ONP emergency eye clinic when practising within a defined scope of practice. An
      ONP-led emergency eye clinic is a viable addition to acute ophthalmic eye care in
      Australia.

PMID- 16402952
TI  - Utility values and myopia in medical students in Singapore.
AB  - PURPOSE: Although technologies to correct myopia have progressed in recent years,
      it is not known how cost-effective such technologies are. In this paper, utility
      values of myopic medical students in Singapore were ascertained as a first step
      to deriving weights for quality adjustment in future cost-effectiveness studies
      of such technologies. METHODS: Students (n = 120) aged 18-22 years with myopia
      (spherical equivalent at least -0.5 D) from Singapore's sole medical school were
      recruited. Information on lifetime intention to undergo refractive surgery,
      contact lens use, proportion of waking time spent wearing corrective devices, and
      utility values using the time trade-off and standard gamble for death methods,
      were obtained. RESULTS: The mean utility values for time trade-off and standard
      gamble were 0.97 (95% confidence interval 0.96-0.98, median 1.00) and 0.99 (95%
      confidence interval 0.98-0.99, median 1.00), respectively. Utility values were
      significantly higher among those who reported a probability of less than 50% that
      they would undergo refractive surgery within their lifetime, compared with those
      who reported a probability of 50% or more (means 0.98 vs. 0.95, P < 0.001).
      CONCLUSION: Utility values in myopic medical students obtained in this study
      appear to be relatively high, compared with those obtained for other ophthalmic
      conditions.

PMID- 16402953
TI  - Diagnostic vitreous biopsy in patients with uveitis: a useful investigation?
AB  - PURPOSE: To assess whether the results of microbial and cytological
      investigations of vitreous biopsy specimens are useful in the management of
      patients with intraocular inflammation. METHOD: A retrospective review of the
      medical records of 59 consecutive patients from consulting rooms, outpatient
      clinics and inpatient consultation who underwent intravitreal sampling between
      January 1997 and December 2003. Results of the biopsies were examined to
      determine if they altered management of the patient. RESULTS: The clinical
      diagnosis was correct in 37 of 59 patients (62.7%) with ocular inflammation. The
      organism was identified in 50% (7/14) of vitreous biopsies in patients with
      postoperative endophthalmitis. Of patients with endogenous bacterial
      endophthalmitis 16.7% (1/6) had the diagnosis confirmed by vitreous tap and 83.3%
      (5/6) had positive cultures from other sites that provided the diagnosis. Of the
      fungal endophthalmitis 80% (4/5) grew the fungus from the vitreous biopsy. Viral
      polymerase chain reaction identified the causative organism in 87.5% (7/8) of
      patients with clinical diagnosis of viral infection. 30.8% (4/13) vitreous
      biopsies in patients with clinically suspected masquerade syndromes were
      diagnosed as lymphoma. Vitreous biopsy results altered management significantly
      in seven (11.9%) patients. These patients included toxoplasmosis that was thought
      to be viral retinitis; malignant melanoma thought to be fungal endophthalmitis;
      chronic inflammation secondary to retinal detachment that was thought to be a
      neoplasm; three patients with infective endophthalmitis thought to be idiopathic
      uveitis and a patient with known lung carcinoma thought to have metastases who
      had lymphoma. In 67.8% (40/59) the vitreous sample helped to either confirm the
      diagnosis or exclude an infective cause. Complications from vitrectomy were
      hypotony (1/29) and retinal detachment (1/29). CONCLUSION: Clinical diagnosis
      based on examination findings and vitreous biopsy is highly accurate. Vitreous
      sampling altered the management of seven of 59 patients. Vitreous biopsy is a
      safe and useful method for diagnosing and excluding malignancy and infection in
      patients with ocular inflammation. Viral polymerase chain reaction is highly
      sensitive and accurate. The sensitivity of microbiological culture techniques for
      bacteria and fungi limits their usefulness.

PMID- 16402954
TI  - Extensive submacular haemorrhage in polypoidal choroidal vasculopathy managed by
      sequential gas displacement and photodynamic therapy: a pilot study of one-year
      follow up.
AB  - BACKGROUND: Polypoidal choroidal vasculopathy (PCV) with peculiar vascular
      lesions presents frequently as recurrent submacular haemorrhage. The best
      treatment is still not certain. It is the authors' objective to evaluate the 1
      year safety and efficacy of photodynamic therapy (PDT) using verteporfin for
      persistent macular PCV after pneumatic displacement of the massive submacular
      haemorrhage with intravitreal perfluoropropane (C(3)F(8)). METHODS: A
      prospective, non-comparative, interventional case series on patients with
      extensive and thick submacular haemorrhage secondary to PCV, which was displaced
      pneumatically with intravitreal pure 0.4 ml C(3)F(8). Fluorescein angiography and
      indocyanine green angiography were repeated 1-2 weeks later to delineate any
      persistent active leaking polypoidal lesions, which were then treated with PDT.
      Retreatment might be considered in each follow up at every 3 months. RESULTS: Six
      eyes of six patients with the mean age of 53.6 years had been recruited and
      completed 1-year follow up. The mean baseline Snellen equivalent best-corrected
      visual acuity (BCVA) was 6/92 and the mean final BCVA at 1 year was 6/17. The
      mean improvement in logMAR BCVA after the sequential treatments was seven lines
      (range +3 to +19 lines) (Wilcoxon signed-ranks test, P = 0.03). All patients had
      at least moderate visual gains. No patient suffered serious complications from
      PDT. CONCLUSIONS: This first report on combined treatment with intravitreal gas
      injection and sequential PDT on PCV seems to be a well-tolerated option. Further
      comparative studies with larger sample size and longer follow up are warranted.

PMID- 16402955
TI  - Posterior chamber compartments demonstrated by optical coherence tomography, in
      silicone-filled eyes, following macular hole surgery.
AB  - PURPOSE: To report visualization with optical coherence tomography of a prefoveal
      space in silicone oil-filled eyes following surgery for idiopathic macular hole.
      METHODS: Seven eyes of seven consecutive patients undergoing macular hole surgery
      with silicone oil tamponade were prospectively evaluated with optical coherence
      tomography preoperatively, on the first postoperative day, after 6 weeks and
      before removal of silicone oil. RESULTS: In all seven eyes the posterior face of
      the silicone oil bubble was visualized with optical coherence tomography. In all
      of these patients, who had a silicone oil fill of over 90%, the silicone oil
      bubble in the upright position did not conform to the foveal depression. Closure
      of the macular hole was achieved in all seven eyes after one operation.
      CONCLUSIONS: Macular hole closure can occur without complete tamponade of the
      central fovea. A prefoveal space can be visualized in silicone oil-filled eyes.
      Concentration of growth factors, adjuvants and indocyanine green in this
      compartment may influence postoperative visual outcome, as may changes in retinal
      homeostasis induced by removal of silicone oil.

PMID- 16402956
TI  - Outcome of corneal transplant rejection: a 10-year study.
AB  - PURPOSE: To study the incidence of graft rejection and the predictive factors for
      its reversibility. METHODS: It is a retrospective study of 1927 consecutive
      penetrating keratoplasties performed between January 1990 and January 2000 with
      more than 6 months follow up. A total of 224 rejection episodes were noted in 183
      patients. Of these, 184 first rejection episodes were included in this study.
      RESULTS: The incidence of first rejection episode was 9.55%. Of patients 87% were
      symptomatic during the episode with vision loss being the commonest. The average
      time of onset of rejection was 15.25 +/- 14.4 months (median 11.7 months). In
      total, 53.3% of rejections occurred within 1 year after surgery. Of the patients
      who completed minimum 3 months follow up after the rejection episode, the rate of
      reversibility was 63.3%. Major predictive factors for a poor outcome after
      rejection were repeated grafting and associated anterior vitrectomy during
      surgery. The reversibility of the episode did not differ significantly with the
      modality of treatment used, but treatment with intravenous steroids within 7 days
      of onset of rejection may have a role in reducing the recurrences of rejection
      episodes, thus increasing the graft survival. CONCLUSION: Regrafts and associated
      anterior vitrectomy were significant risk factors for a poor outcome following
      rejection episode.

PMID- 16402957
TI  - D-TAT transporter as an ocular peptide delivery system.
AB  - BACKGROUND: Future treatment for genetic diseases may involve the replacement of
      malfunctioning genes through virus-mediated gene therapy. However, this approach
      is plagued with many problems, both ethical and scientific. Therefore,
      alternative treatments based on new molecules may represent a safer option.
      Molecular treatment of many eye diseases will need to bring active molecules into
      the photoreceptors. Recently, the trans-activator protein (TAT) human
      immunodeficiency virus type 1 (HIV-1) transcriptional factor has proven to be
      effective in transporting molecules across cellular membranes. The half-life of
      these molecules does not exceed 48 hours. The potential use of the retro-inverso
      form of the TAT (D-TAT) peptide, the protein transducing domain of the HIV-1
      transcriptional factor, as a molecular transporter was investigated. METHODS:
      FITC-labelled D-TAT (D-TAT FITC) was applied to the 661W murine photoreceptor
      cell line in culture. The labelled peptide was also injected into the vitreous
      body or the subretinal space of adult mice. Cells and cryosections of eyes were
      analysed under fluorescence microscopy at various time points after peptide
      treatment. Coimmunostaining with various antibodies was performed in order to
      characterize the transduces cells. RESULTS: D-TAT was effective in transducing
      photoreceptor cells in culture. Transduction of D-TAT FITC was also effective
      when injected into the vitreous or subretinal space and was observed for a longer
      period of time than L-TAT FITC. CONCLUSIONS: The retro-inverso form of the TAT
      sequence is effective in transducing cells from various compartments of the eye.
      After 14 days, the D-TAT FITC was clearly visible in the retina whereas L-TAT
      FITC had almost disappeared. The D-TAT peptide represents an interesting
      molecular transporter that, when coupled to a specific effector, may have
      potential therapeutic future, especially when a long-lasting action is needed.

PMID- 16402958
TI  - Herpes zoster ophthalmicus: presenting as giant-cell arteritis.
AB  - A 74-year-old woman was referred to the authors' clinic with a 1-week suspicion
      of giant-cell arteritis. Uncomplicated, bilateral temporal artery biopsies were
      performed 3 days after admission for therapy. Four hours after the procedure she
      developed vesicular lesions of the face compatible with herpes zoster
      ophthalmicus. The temporal artery biopsy revealed perineural lymphocytic
      aggregation. Both giant-cell arteritis and herpes zoster ophthalmicus form part
      of the differential diagnosis in elderly patients with headache. In such cases,
      clues from a temporal artery biopsy may aid in diagnosis of herpes zoster. In
      addition, the patient in this case developed the rash 10 days after onset of
      symptoms, which is rare as the average time from onset of symptoms to rash in
      zoster is 3-5 days.

PMID- 16402959
TI  - Pleomorphic adenoma of the lacrimal gland in a nine-year-old child.
AB  - A case of a 9-year-old child with pleomorphic adenoma of the lacrimal gland is
      described. This tumour is usually found in adults; cases younger than 10 years of
      age have proved to be extremely rare. Because of its age distribution,
      pleomorphic adenoma of the lacrimal gland is usually overlooked as a possible
      cause of unilateral proptosis in children. Also, the history of disease provided
      by the family may be incorrect, possibly leading to misdiagnosis by the
      ophthalmologist.

PMID- 16402960
TI  - Centennial review of corneal transplantation.
AB  - Abstract One hundred years ago, on 7 December 1905, Dr Eduard Zirm performed the
      world's first successful human corneal transplant. This significant milestone was
      achieved only after many decades of unsuccessful trial and error; however, it did
      not lead to relatively 'routine' keratoplasty success for several more decades.
      The idea of replacing an opaque cornea had been suggested for centuries, and had
      stimulated theoretical approaches to the problem by many esteemed physicians
      throughout history. However, little practical progress was made in the ultimate
      realization of the dream until the 19th century when pioneering surgeons pursued
      extensive studies in relation to both animal and human 'keratoplasty'. Clinical
      progress and scientific insight developed slowly, and it was ultimately due to
      parallel advances in medicine such as anaesthesia and antisepsis that Zirm's
      success was finally achieved. Key concepts were enshrined such as the use of
      fresh tissue from the same species, careful placement and handling of tissue, and
      the development of specialized instrumentation such as the circular trephine. In
      the latter half of the 20th century, many 'masters' of corneal surgery evolved
      significant refinements in technique and instrumentation with the development of
      corticosteroids, antibiotics, surgical microscopes, improved trephines,
      viscoelastics and suture materials, that enable this delicate procedure to be
      routinely performed with the prospect of success. There are still limitations to
      corneal transplantation, and corneal allograft rejection still poses the greatest
      challenge to the modern corneal surgeon. In the foreseeable future it may be in
      the laboratory, rather than the theatre, that further milestones will be
      achieved. This review aims to highlight the significant milestones in the rich
      history of corneal transplantation, and to pay tribute to the many inspired and
      dedicated individuals involved in the development of keratoplasty to a point
      where the procedure is now a standard tool in the repertoire of ophthalmic
      surgery and more than a million people have enjoyed restoration of useful sight.

PMID- 16402962
TI  - Intralenticular foreign body: a D-Day reminder.
AB  - Intralenticular foreign bodies are not uncommon after penetrating eye injuries.
      This is an observational case report where a patient was found to have an
      embedded lenticular foreign body for more than 60 years. Following such a long
      period of time the patient has not experienced any significant cataract formation
      or compromised ocular function due to the foreign body.

PMID- 16402963
TI  - Traumatic cataract and intralenticular foreign body.
AB  - Traumatic cataracts resulting from penetrating injuries occur most frequently
      from projectile metallic foreign bodies. The majority of intraocular foreign
      bodies cause sight-threatening damage including traumatic cataract in up to 25%
      of the cases. A case of traumatic cataract and retained intralenticular foreign
      body that was removed successfully with phacoemulsification and foldable
      intraocular lens implantation in the capsular bag is described. This case report
      highlights the benefit in planning surgical management as a two-staged procedure
      after appropriate investigations.

PMID- 16402964
TI  - Orbital foreign body masquerading as conjunctival melanoma 60 years after injury.
AB  - A 74-year-old man presented with a 6-month history of a pigmented conjunctival
      lesion on his left eye. The lesion was initially suspicious for conjunctival
      melanoma. The patient admitted to a remote history of trauma from a airgun pellet
      over 60 years ago. Anterior examination revealed a 6 x 6 mm pigmented left
      conjunctival lesion and B-scan of the lesion was suggestive of a retained orbital
      foreign body. The lesion was removed through a transcaruncular medial orbitomy
      and pathology showed a retained orbital foreign body. A newly pigmented
      conjunctival lesion although initially concerning for melanoma represented a
      retained orbital body that surfaced many years after the initial orbital trauma.

PMID- 16402965
TI  - Asymptomatic choroidal granulomas in common variable immunodeficiency.
AB  - Common variable immunodeficiency disease represents the most common cause of
      significant antibody deficiency in adults. It is a heterogeneous group of
      disorders that can be sporadic or familial with various modes of inheritance with
      defects in B-cell function, regulatory T-cells and macrophage function all being
      reported. Herein a case of asymptomatic bilateral choroidal granulomatous disease
      in a 27-year-old man with common variable immunodeficiency disease is described.

PMID- 16402967
TI  - Unilateral amiodarone keratopathy.
AB  - Vortex keratopathy is characterized by bilateral symmetrical superficial corneal
      deposits in a vortex pattern. It is the most common ocular finding among patients
      being treated with amiodarone. An unusual case of unilateral amiodarone vortex
      keratopathy in an elderly woman with corneal dysplasia in the second eye is
      presented. The pathophysiology of amiodarone keratopathy is explored, and a cause
      for the unilateral keratopathy in this patient proposed.

PMID- 16402966
TI  - Presentation of intraocular foreign body 25 years after the event.
AB  - Delayed presentation of retained intraocular foreign body is a diagnostic and
      therapeutic challenge to the ophthalmologist. Herein a case of a man presenting
      25 five years after initial injury with a retained metallic foreign body adjacent
      to the optic disc is described.

PMID- 16402968
TI  - Band-like opacity in the corneas of abattoir-acquired pig eyes.
AB  - In the course of an investigation into the distribution of immune cells in the
      porcine cornea, a band-like lesion on the cornea of two-thirds of the eyes
      acquired from the local abattoir was noted. Histological investigations revealed
      an area of corneal epithelium debridement with no obvious other pathological
      changes. Discussions with abattoir staff soon revealed the cause of the lesions
      to be the scalding process that all pig carcasses undergo immediately post-mortem
      that serves to remove unwanted hair and reduce skin-dwelling bacterial
      contamination. We concluded that the band-like opacity was the result of thermal
      injury to the anterior surface of the cornea between the open eyelids. It is
      hoped that this short communication will act as a cautionary note to other
      investigators who currently use or are considering using porcine eyes in research
      or as a model in surgical training and who may be unaware of the conventional
      handling procedures in pig abattoirs.

PMID- 16402969
TI  - In situ adenocarcinoma ex pleomorphic adenoma of the lacrimal gland.
AB  - A case of an in situ adenocarcinoma of the lacrimal gland that developed in a
      recurring pleomorphic adenoma is presented. Six years after incomplete resection
      of a pleomorphic adenoma, the patient complained of a progressive swelling of her
      right upper eyelid without pain or diplopia. An orbital computerized tomography
      scan showed an inhomogeneous mass in the right lacrimal gland region without bone
      involvement. After local excision of the in situ adenocarcinoma ex pleomorphic
      adenoma, the tumour has been in control for over 6 years.

PMID- 16402970
TI  - Bilateral exudative retinal detachments as the presenting features of idiopathic
      orbital inflammation.
AB  - Idiopathic orbital inflammation, also known as orbital pseudotumour, is a term
      describing a spectrum of idiopathic, non-neoplastic, non-infectious, space
      occupying orbital lesion without identifiable local or systemic cause. This
      disease occurs mainly in young adults and typically presents with acute
      proptosis, chemosis and limited extraocular movement. Herein an unusual case of
      idiopathic orbital inflammation presenting with bilateral exudative retinal
      detachment in a 9-year-old girl is described. It demonstrates that prompt
      diagnosis and corticosteroid treatment can yield good clinical response and
      significant visual recovery.

PMID- 16402971
TI  - Smokers' veins: a useful clinical sign--comment.

PMID- 16402972
TI  - Profound sweating episodes and latanoprost.

PMID- 16402974
TI  - A review of the evidence base for the management of thyroid disease. A summary of
      the proceedings of the 8th annual evidence-based medicine day, Freeman Hospital,
      Newcastle, 4 November 2004.

PMID- 16402975
TI  - Acute complications of otitis media in adults.
AB  - OBJECTIVES: To establish the incidence, current treatment and outcome of adult
      patients with acute intratemporal and intracranial complications of otitis media
      (OM). DESIGN: A retrospective chart review with a sent questionnaire. SETTING:
      Tertiary referral centre, University hospital. PARTICIPANTS: Adult patients
      treated for acute intratemporal and intracranial complications of OM over the
      past 15 years (1990-2004) in the study hospital. MAIN OUTCOME MEASURES:
      Incidence, treatment and outcome of patients with intratemporal and intracranial
      complications of OM. RESULTS: Fifty patients aged 16-75 years were treated. The
      annual age-adjusted incidence of acute intratemporal and intracranial
      complications was 0.32/100 000. Forty-one (82%) of the complications were
      intratemporal and nine (18%) were intracranial. The ear disease behind the acute
      complication was acute otitis media (AOM) in 80% (40/50), chronic otitis media
      (COM) in 12% (6/50) and COM with cholesteatoma in 8% (4/50). Mastoiditis was
      complicated by subperiosteal abscess, labyrinthitis and facial paresis in 7%
      (3/41), 15% (6/41) and 32% (13/41) respectively. Mastoidectomy was performed on
      56% (28/50) of the patients. Four (44%) of the intracranial complications were
      intracranial abscesses, four (44%) were meningitis and one (11%) was sinus
      thrombosis. Permanent hearing loss occurred in 13 (26%) patients and one patient
      died due to otogenic meningitis. CONCLUSIONS: Severe complications of the OM in
      adults are rare in Finland. The commonest cause is AOM rather than COM. Operative
      treatment is predominantly needed for intracranial complications and
      intratemporal abscesses. Complications of OM are still associated with
      considerable morbidity, and early recognition is most likely to form the basis
      for effective treatment.

PMID- 16402976
TI  - Noise-induced hearing loss is exacerbated by long-term smoking.
AB  - OBJECTIVE: To analyse the influence of long-term smoking on the hearing threshold
      of individuals subjected to occupational noise exposure. DESIGN: Prospective
      observational cohort study. SETTING: Occupational health examination of noise
      exposed employees in the brick manufacturing industry. PARTICIPANTS: A study
      group of long-term smokers (n = 30) and a control group of non-smokers (n = 58)
      were identified from a population of 227 male noise-exposed employees.
      Individuals of both groups were employed for 10 years or more at a single brick
      manufacturing plant. Data on noise exposure, smoking habits, medical and
      otological history were collected and standard pure tone audiometry was obtained.
      Exclusion criteria included asymmetrical or conductive hearing loss, uncontrolled
      systemic illnesses, history of head injury, chronic middle ear pathology or major
      ear operations. MAIN OUTCOME MEASURE: Pure tone audiometry. RESULTS: Both groups
      had similar mean age and total duration of occupational noise exposure. The
      median age-corrected hearing thresholds at 3 and 4 kHz in the smokers group were
      significantly higher (approximately 7dB) than those in the non-smokers group. No
      statistical difference in the hearing thresholds between both groups was found in
      any other tested frequency (0.5, 1, 2, 6 and 8 kHz). CONCLUSION: Long-term
      smokers with occupational noise exposure may, on the basis of this limited study,
      have a higher risk of developing permanent hearing loss at 3 and 4 kHz when
      compared with non-smokers with a similar occupational history.

PMID- 16402977
TI  - The association of antidiuretic hormone levels with an attack of Meniere's
      disease.
AB  - OBJECTIVES: An elevation of the plasma antidiuretic hormone (ADH) levels has
      frequently been observed in Meniere's disease patients. However, little is known
      regarding the mechanism behind such an elevation of ADH level in Meniere's
      disease patients. Therefore, we measured the plasma ADH in Meniere's disease
      patients and other vertigo patients to elucidate the association between the ADH
      levels, stress levels and the development of Meniere's symptom. DESIGN AND
      SETTING: The plasma ADH levels and plasma osmotic pressure were determined in 23
      definite Meniere's disease patients and 160 patients with other types of
      vertigo/dizziness. All participants were administered questionnaire regarding
      their psychological status including their stress levels. RESULTS: The ADH levels
      of Meniere's disease patients in the acute phase (5.80 +/- 1.37 pg/mL) were
      significantly higher in comparison with that of Meniere's disease patients in the
      remission phase (2.26 +/- 0.41 pg/mL) (P < 0.05). In other peripheral vertigo
      patients, the ADH level in the acute phase (1.71 +/- 0.23 pg/mL) was not
      significantly different from that in the remission phase (1.45 +/- 0.15 pg/mL).
      Meniere's disease patients in the acute phase had a significantly higher stress
      score (114 +/- 23) than Meniere's disease patients in the remission phase (56 +/-
      13) (P < 0.05). However, there was no significant correlation between their
      stress score and the ADH levels. CONCLUSIONS: These results suggest that the
      elevation of the plasma ADH levels in Meniere's disease patients in the acute
      phase is, therefore, associated with the pathogenesis of Meniere's disease
      attacks rather than with stress.

PMID- 16402978
TI  - Is ultrasound useful for evaluating paediatric inflammatory neck masses?
AB  - OBJECTIVE: To determine the accuracy of ultrasound in detecting the presence of
      pus in a neck mass in children. DESIGN: Retrospective case sheet review. SETTING:
      A district general hospital. PARTICIPANTS: Children admitted from January 2000 to
      January 2004 with an acute cervical mass who were investigated by
      ultrasonography. MAIN OUTCOME MEASURES: The presence of a clinically relevant
      abscess that did not respond to clinical management was used to determine the
      accuracy of the ultrasound result. RESULTS: The sensitivity of ultrasound in the
      detection of an abscess was 65% and the specificity 88%. The predictive value of
      a positive ultrasound result was 81% and the predictive value of a negative test
      77%. CONCLUSIONS: Ultrasound is a useful modality in the evaluation of acute
      cervical masses but is observer dependent and has a relatively low sensitivity in
      detecting whether or not pus is present. The clinical indicators for the presence
      of an abscess are discussed and clinicians should combine clinical findings with
      the ultrasound findings in order to determine treatment.

PMID- 16402979
TI  - Psychological coping style versus disease extent, tumour treatment and quality of
      life in successfully treated head and neck squamous cell carcinoma patients.
AB  - OBJECTIVES: To study self-reported coping style by the COPE questionnaire and the
      association to tumour node distant metastasis (TNM) stage, received treatment and
      health-related quality of life (HRQoL) in a population of successfully treated
      head and neck squamous cell carcinoma (HNSCC) patients. DESIGN: Disease free
      HNSCC patients were interviewed during a regular outpatient visit to the
      Department. SETTING: All patients <80 years who had been diagnosed with HNSCC, in
      Western Norway, in the period from 1992 to 1997 and who were disease free in the
      year 2000 were included. MAIN OUTCOME MEASURES: The HNSCC patients were studied
      by the European organization for research and treatment of cancer quality of life
      (QoL) questionnaire and by the COPE questionnaire from which coping styles
      profiles were extracted. Clinical and socio-demographic variables were also
      gathered. RESULTS: Level of problem focused coping style was associated with the
      T stage and whether or not the patient was given neck radiotherapy. An avoidance
      focused coping style was generally associated with lowered HRQoL. Employment of
      emotional focused coping was associated with low HRQoL among the patients treated
      with surgery only, and associated with increased HRQoL among patients treated
      with radiation therapy only. The associations between HRQoL and coping style
      levels were stronger for HRQoL indexes reflecting cognitive/emotional function
      than for HRQoL indexes reflecting physical function. CONCLUSIONS: In former HNSCC
      patients, level of problem focused coping style was associated with the T stage
      and if given neck radiotherapy. Level of avoidance coping was inversely
      associated with the HRQoL, and level of emotional coping was associated with
      HRQoL in a complex manner.

PMID- 16402980
TI  - Endoscopic sphenopalatine artery ligation--when, why and how to do it. An on-line
      video tutorial.
AB  - KEYPOINTS: Endoscopic ligation of the sphenopalatine artery (ESPAL) has recently
      become the treatment of choice for refractory epistaxis. This paper reviews the
      background, indications and potential complications of ESPAL. The main focus of
      this article is an online video tutorial on the anatomy and surgical technique of
      ESPAL. Web links lead to video clips of operative steps and therefore this paper
      should be read in front of a computer with access to the Internet. To study the
      techniques the links detailed below should be followed. (For computers running
      RealPlayer software the .wmv extension in each of these links should be replaced
      with the .rm extension.) * Incision,
      http://nhsgg.org.uk/content/streams/Figure3.wmv * Flap elevation,
      http://nhsgg.org.uk/content/streams/Figure4.wmv * Pedicle location,
      http://www.nhsgg.org.uk/content/streams/Figure5.wmv * Clip application,
      http://www.nhsgg.org.uk/content/streams/Figure6.wmv.

PMID- 16402983
TI  - How we do it: transnasal fibreoptic oesophagoscopy.
AB  - KEYPOINTS: Transnasal fibreoptic oesophagoscopy (TFO) allows the upper
      aerodigestive tract, from the nasal vestibule to the gastric cardia to be
      examined in the outpatients department without sedation. This permits patients
      with symptoms of upper aerodigestive pathology to be investigated at the initial
      consultation without the need for inpatient endoscopy or swallow studies. The
      technique is easily learned, and is statistically comparable with standard
      flexible nasoendoscopy in respect of procedural pain and discomfort. It is highly
      cost-efficient, paying for itself within 1 year, and thereafter leading to cost
      savings of over 80%. Its role can be expanded to encompass investigating patients
      with potentially malignant disease processes, as well as outpatients
      "panendoscopy" and biopsy, and a number of therapeutic interventions.

PMID- 16402984
TI  - How we do it: The role of trans-nasal flexible laryngo-oesophagoscopy (TNFLO) in
      ENT: one year's experience in a head and neck orientated practice in the UK.
AB  - KEYPOINTS: Transnasal flexible laryngo-oesophagoscopy (TNFLO) is a safe and well
      tolerated procedure that may be performed in a procedure room in the outpatient
      or day-case/main theatre setting. It requires a local anaesthetic and no
      sedation. It may be used to histologically diagnose or exclude pathology from the
      nose to the gastro-oesophageal junction. It provides a "one stop" diagnosis
      service, reducing diagnostic delays, the need for endoscopy under general
      anaesthesia, barium swallows and follow-up outpatient appointments. Therapeutic
      procedures such as vocal cord medialization, endolaryngeal laser surgery,
      insertion of speech prostheses and foreign body removal may be performed without
      general anaesthesia.

PMID- 16402985
TI  - How we do it: "The oral tube area method": a new method for self-assessment of
      nasal resistance.
AB  - KEYPOINTS: Breathing orally through a tube, 20 subjects compared their sensation
      of air resistance in the tube with their sensation of resistance breathing
      through the nose. By changing the internal cross-sectional area in the tube the
      subjects could choose an oral tube area where they felt the same resistance in
      the tube as in the nose. Expressed by the chosen oral tube area we had a
      measurement of the nasal resistance. The method can measure changes in nasal
      resistance. The method is inexpensive and easy to perform.

PMID- 16402987
TI  - Patients and the internet: are websites on glue ear readable?

PMID- 16402986
TI  - How we do it: the anterior thoraco-cervical approach to tumours of the thoracic
      inlet.
AB  - KEYPOINTS: Tumours that arise in the thoracic inlet and superior mediastinum may
      be benign or malignant and present the surgeon with a difficult problem of
      access. The standard approach to the thoracic inlet from below offers limited
      exposure to the vascular and neural structures superior to the tumours. The
      anterior thoraco-cervical approach to the root of the neck and superior
      mediastinum combines the anterior cervical approach with a limited upper median
      sternotomy. If further access is required to achieve surgical clearance a full
      sternotomy split can be performed. The approach offers excellent exposure and
      helps to facilitate complete resection of benign and malignant tumours, which
      would otherwise be deemed inoperable or difficult to resect completely through
      other standard approaches. In contrast to previously described anterior
      transcervical thoracic approaches which required resection of part of the
      clavicle or manubrium as well as thoracotomy with increased morbidity, the
      anterior thoraco-cervical approach is associated with little morbidity and the
      postoperative stay is short.

PMID- 16402988
TI  - Nasal preparation.

PMID- 16402989
TI  - How to avoid spillage of pus when draining peritonsillar abscess.

PMID- 16402990
TI  - Work force planning: will the aspirations of the present group of Otolaryngology
      Specialist Registrars meet the need?

PMID- 16402991
TI  - Nerve monitoring in ENT surgery.

PMID- 16402993
TI  - Double-blind randomized control trial of coblation tonsillotomy versus coblation
      tonsillectomy on post-operative pain in children.

PMID- 16402995
TI  - Double-blind randomized controlled study of coblation tonsillotomy versus
      coblation tonsillectomy on post-operative pain.

PMID- 16402996
TI  - The use of camera mobile phone to assess emergency ENT radiological
      investigations.

PMID- 16403000
TI  - Jain tonsil "A" frame--a solution to slipping rods.

PMID- 16402998
TI  - Jain tonsil "A" frame--a solution to slipping rods.

PMID- 16403003
TI  - Arterial stiffening and cardiac hypertrophy in a new rat model of type 2
      diabetes.
AB  - BACKGROUND: We determined the effects of NIDDM on haemodynamic parameters
      describing arterial wall elasticity and cardiac hypertrophy in rats administered
      streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis.
      METHODS: Male Wistar rats at 2 months were administered intraperitoneally 180 mg
      kg(-1) of NA, 30 min before an intravenous injection of 50 mg kg(-1) STZ, to
      induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and
      8 weeks after induction of diabetes, and compared with untreated age-matched
      controls. Pulsatile aortic pressure and flow signals were measured by a high
      fidelity pressure sensor and electromagnetic flow probe, respectively, and were
      then subjected to Fourier transformation for the analysis of aortic input
      impedance. RESULTS: In each diabetic group, the experimental syndrome was
      characterized by a moderate and stable hyperglycaemia and a relative deficiency
      of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats
      showed a decrease in cardiac output in the absence of any significant changes in
      mean aortic pressure, having increased total peripheral resistance. The diabetic
      syndrome at 8 weeks also contributed to an increase in aortic characteristic
      impedance, from 1.49 +/- 0.33 (mean +/- SD) to 1.95 +/- 0.28 mmHg s mL(-1) (P <
      0.05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile,
      the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor
      (0.46 +/- 0.09 vs. 0.61 +/- 0.13, P < 0.05) and decreased wave transit time (25.8
      +/- 3.8 vs. 20.6 +/- 2.8 ms, P < 0.05). Ratio of the left ventricular weight to
      body weight was also enhanced in the 8-week STZ-NA diabetic rats. CONCLUSION: The
      heavy intensity with early return of the pulse wave reflection may augment
      systolic load of the left ventricle coupled to the arterial system, leading to
      cardiac hypertrophy in the rats at 8 weeks after following STZ and NA
      administration.

PMID- 16403004
TI  - BNP and N-terminal proBNP are both extracted in the normal kidney.
AB  - BACKGROUND: Increased plasma concentrations of cardiac-derived B-type natriuretic
      peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both
      associated with left ventricular dysfunction. Information on the regional
      elimination of the peptides is, however, still scarce. We therefore examined the
      renal and peripheral extraction of N-terminal proBNP and BNP. MATERIALS AND
      METHODS: The study comprised 18 patients with essential arterial hypertension, 51
      with cirrhosis, and 18 control patients without kidney or liver disease. All
      patients underwent a haemodynamic investigation with catheterization of the
      femoral artery and femoral and renal veins. Blood sampling from the catheters
      allowed determination of the arteriovenous extraction ratio of N-terminal proBNP
      and BNP. RESULTS: Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L(
      1), NS) nor the BNP plasma concentrations (4, 12, 9 pmol L(-1), NS) differed
      between the patient groups. In addition, similar renal extractions were observed
      in the groups. The renal extraction of N-terminal proBNP (0.16) was not different
      from that of BNP (0.16). In contrast, the N-terminal proBNP extraction in the
      lower extremity was markedly lower compared with BNP (0.00 vs. 0.125, P = 0.007).
      CONCLUSIONS: A comparable renal elimination of N-terminal proBNP and BNP is
      contrasted by a selective extraction of BNP in the lower extremity. Our results
      suggest a different elimination mechanism in the renal and peripheral
      circulation, which partly may explain the higher N-terminal proBNP compared with
      BNP concentrations in normal plasma.

PMID- 16403005
TI  - Lipoprotein lipase activity/mass ratio is higher in omental than in subcutaneous
      adipose tissue.
AB  - BACKGROUND: Lipoprotein lipase (LPL) is important for lipid deposition in adipose
      tissue (AT) and responds rapidly to changes in the nutritional state. Animal
      experiments indicate that short-term regulation of LPL is mainly post
      translational. Different processing of LPL in different AT depots may play a role
      in the distribution of lipids in the body. MATERIALS AND METHODS: Lipoprotein
      lipase mRNA, mass and activity were measured in pieces of omental adipose tissue
      (OAT) and subcutaneous adipose tissue (SAT) from 15 subjects undergoing
      gastrointestinal surgery (four male and 11 female subjects, mean age 54 +/- 5
      years, BMI 28 +/- 2 kg m(-2)). RESULTS: Lipoprotein lipase activity was higher in
      OAT than in SAT (18 +/- 2.1 compared with 12 +/- 1.6 mU g(-1), P < 0.01), whereas
      LPL mass was lower in OAT than in SAT (100 +/- 9 compared with 137 +/- 16 mU g(
      1), P < 0.05). Consequently, the specific LPL activity (ratio of activity over
      mass) was approximately twofold greater in OAT compared with SAT. There was
      correlation between LPL mRNA and LPL activity in SAT (P < 0.05) and a similar
      tendency in OAT (P = 0.08). There were strong correlations (P < 0.01) for mRNA
      abundance as well as for LPL activity between the two depots. In contrast there
      was no correlation between the LPL mass and LPL mRNA or activity in any of the
      depots. CONCLUSIONS: These results indicate that long-term regulation, as
      reflected in the mRNA abundance, is similar in the two types of adipose tissue.
      The displayed activity reflects the mRNA abundance and the fraction of newly
      synthesized LPL molecules which the post-translational mechanism allows to
      become/remain active. This fraction was on average twofold greater in OAT
      compared with SAT.

PMID- 16403006
TI  - Impaired beta-cell function in lean normotolerant former gestational diabetic
      women.
AB  - BACKGROUND: Former gestational diabetes (fGDM) constitutes a risk condition for
      the development of Type 2 diabetes. Former gestational diabetes is often
      characterized by obesity and hyperglycaemia, which may be concomitant and
      independent risk factors. MATERIALS AND METHODS: To assess insulin sensitivity
      and beta-cell function in fGDM uncomplicated by obesity and hyperglycaemia, we
      studied 24 lean fGDM women and 23 control women matched for age (30.7 +/- 0.7
      years, whole cohort), body mass index (22.2 +/- 0.3 kg m(-2)), and
      indistinguishable for plasma glucose both at fasting and at 120 min. Several
      insulin sensitivity and beta-cell function indices were computed: homeostasis
      model assessment insulin resistance index (HOMA-R), insulin sensitivity index
      derived from an oral glucose tolerance test (OGIS), insulinogenic index, other
      empirical indices of insulin secretion and beta-cell function, and indices
      obtained using a beta-cell model. RESULTS: Though the majority of indices, and in
      particular insulin sensitivity (HOMA-R: 1.35 +/- 0.13 vs. 1.65 +/- 0.14; OGIS:
      492.7 +/- 6.3 vs. 496.4 +/- 9.4 mL min(-1) m(-2)), were not significantly
      different in the two groups, the beta-cell glucose sensitivity obtained by
      modelling analysis was lower in fGDM (108 +/- 14 vs. 165 +/- 22 pmol min(-1) m(
      2) mM(-1), P = 0.031). CONCLUSIONS: Impairment of beta-cell glucose sensitivity
      may be an intrinsic risk factor in fGDM independently of obesity and
      hyperglycaemia. Furthermore, we have shown that modelling analysis, in contrast
      to the empirical parameters, may be able to detect early beta-cell alterations in
      fGDM women.

PMID- 16403007
TI  - Kinetics of prebeta1 HDL and alphaHDL in type II diabetic patients.
AB  - BACKGROUND: The aim of this study was to analyze the recycling of high density
      lipoprotein (HDL) in six type II diabetic patients compared with six control
      subjects by endogenous labelling of apolipoprotein A-I (Apo A-I) with stable
      isotope Apo A. MATERIALS AND METHODS: The -I-HDL kinetics were performed by
      infusion of (5.5.5-(2)H3)-leucine for 14 h. The prebeta1 and alphaHDL were
      separated by gel filtration fast protein liquid chromatrography system (FPLC).
      Kinetics of isotopic enrichment of Apo A-I were analyzed with a multi
      compartmental model software (SAAM II, SAAM Institute, Seattle, WA). RESULTS:
      Plasma Apo A-I concentration was decreased in patients with type II diabetes as a
      result of a decrease in Apo A-I-alphaHDL (P < 0.05). Diabetic patients were also
      characterized by an increased relative contribution of Apo A-I in prebeta1 HDL
      (18.3 +/- 2.8% vs 11.9 +/- 3.7%, P < 0.01). The synthetic rate of prebeta1 HDL
      was slightly increased in diabetic patients compared with control (NS) and an
      increase of recycling rate of alpha to prebeta1 HDL was observed (11.67 +/- 3.14
      d(-1) vs 7.09 +/- 4.51 d(-1), P < 0.05). The clearance rate of Apo A-I was higher
      in diabetic patients (P < 0.05 for Apo A-I-prebeta1 HDL and P < 0.005 for Apo A-I
      alphaHDL). CONCLUSION: This study suggests that the usual increase in prebeta1
      HDL in type II diabetic patients is mainly related to an increased conversion
      rate of alpha to prebeta1 HDL.

PMID- 16403008
TI  - Non-haem iron transport in the rat proximal colon.
AB  - BACKGROUND: Only 10% of dietary iron is absorbed in the duodenum which implies
      that 90% (approximately 9 mg day(-1)) reaches the lower small intestine and
      colon. Therefore the purpose of this study was to assess the iron transport
      capacity of the rat proximal colon and to determine whether iron absorption is
      regulated by changes in dietary iron content. MATERIALS AND METHODS: Rats were
      fed for 14 days on either iron adequate (44 mg Fe kg(-1) diet) or iron-deficient
      (< 0.5 mg Fe kg(-1) diet) diets. The 59Fe transport across the colonic epithelium
      and its subsequent appearance in the blood were measured in vivo. In separate
      studies the colon was excised and used to measure divalent metal transporter
      expression. RESULTS: Divalent metal transporter (DMT1) was expressed at the
      apical membrane of the surface epithelium in rat proximal colon. In animals fed
      an iron-deficient diet, DMT1 mRNA and protein expression were increased. This was
      accompanied by a significant increase in tissue 59Fe uptake. CONCLUSIONS: The
      proximal colon can absorb non-haem iron from the intestinal lumen. The purpose of
      this mechanism remains to be elucidated.

PMID- 16403009
TI  - Smad3-null mice lack interstitial cells of Cajal in the colonic wall.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta)/Smad's signalling pathway
      plays a pivotal role in organogenesis, oncogenesis, inflammation, repair and
      fibrosis. The aim of this study was to evaluate the morphology of muscle layers
      and the density and distribution of interstitial cells of Cajal (ICC) in the
      colon of Smad3 knockout mice. MATERIALS AND METHODS: Eighteen Smad3 wild-type
      mice and 12 null mice were sacrificed at age 4 months and the colons were
      collected for histology (Haematoxilin-Eosin, Masson thrichrome and Gomori silver
      staining), morphometry and immunohistochemistry (IHC) analysis. For IHC we used
      the c-Kit, alpha-smooth muscle actine (alpha-SMA), vimentin, desmin and neuronal
      cocktail (S-100, NSE, neurofilament 200) antibodies. RESULTS: When sacrificed,
      40% of the null mice showed different degrees of colon dilatation when compared
      with the wild-type. Histological and morphometric evaluation revealed a
      significant reduction in muscle layer thickness of the colon in all the null mice
      when compared with the wild-type. Immunohistochemistry evaluation showed a marked
      reduction, or even absence, of c-Kit immunoreactivity, which identifies ICC, in
      the colon of all the null mice, compared with the wild-type. CONCLUSIONS: Smad3
      null mice showed a marked reduction, or even absence, of ICC in the colon
      together with a concomitant reduction of intestinal smooth muscle layer
      thickness. This data could account for the colonic dilation observed in
      approximately 40% of the Smad3 null mice. Alteration of intestinal smooth muscle
      layers and ICC could also be involved in the resistance of the Smad3 null mice to
      develop colonic fibrosis.

PMID- 16403010
TI  - Antisense c-myc fragments induce normal differentiation cycles in HL-60 cells.
AB  - BACKGROUND: We have investigated the potential for using antisense technology as
      a means of delivering treatment for acute myeloblastic leukaemia (FAB-M2) by gene
      therapy. MATERIALS AND METHODS: A test recombinant adenovirus vector was
      constructed containing human c-myc antisense fragments to study the effects of
      altering c-myc overexpression in the human HL-60 cell line. Control vector
      contained the human LacZ gene. Transfection efficiency in HL-60 cells was
      determined using control vector in the presence of protamine sulphate and
      multiplicity of infection of 100. Morphological and mechanistic changes were
      assessed using immunohistochemical analysis, flow cytometry and reverse
      transcription-polymerase chain reaction. RESULTS: Transfection efficiency of
      control vector was 79.8% and morphological differences were observed after 72 h
      in culture. The rate of proliferation of HL-60 cells infected with test vector
      was inhibited by 73% compared with control following 6 days in culture. Normal
      terminal differentiation leading to apoptosis was only evident in test vector
      infected cells. Peak apoptosis (34.7%) was detected at day 6 and cell cycle
      arrest at days 2, 4 and 6. Expression of c-fos protein was significantly
      increased in test vector treated cells with a noticeable down-regulation of c-myc
      expression. CONCLUSIONS: These data suggest that transfection of a human HL-60
      cell line with vector containing c-myc antisense fragments could inhibit
      proliferation, but induce differentiation and apoptosis. Thus, we believe that
      further study of this construct is warranted as a potential gene therapy reagent
      for treatment of acute myeloblastic leukaemia.

PMID- 16403012
TI  - Neutrophil and erythroblast regulate the effects of bone marrow cell
      implantation.

PMID- 16403011
TI  - Menstrual cycle symptoms are associated with changes in low-grade inflammation.
AB  - BACKGROUND: A close link between mood, low-grade inflammation and obesity has
      been demonstrated even in healthy subjects. We investigated the relationship
      between changes in physical and psychological symptoms and inflammatory markers
      during the menstrual cycle both in normal weight and in overweight women.
      MATERIALS AND METHODS: Eight healthy normal weight (body mass index 21.6 +/- 1.9
      kg m(-2)) and seven overweight (body mass index 30 +/- 2.4 kg m(-2)) young women
      with normal ovarian function and with no premenstrual syndrome were assessed 15
      times throughout their menstrual cycle. At each time point fasting blood was
      drawn and symptoms were recorded using the Freeman Daily Symptom Record. RESULTS:
      Independent of weight status, the serum concentrations of highly sensitive C
      reactive protein (hs-CRP) and the total scores, in addition to the individual
      four factors (mood, behaviour, pain and physical symptoms), of the Daily Symptom
      Record varied significantly during the menstrual cycle (all P < or = 0.04) and
      paralleled each other. During the menstrual cycle, repeated hs-CRP serum
      concentrations correlated to the corresponding total symptom score and the
      factors mood, behaviour and physical symptoms, independent of both weight status
      and changes in circulating gonadal steroids (all P < or = 0.04). These
      associations were not observed for tumour necrosis factor-alpha serum levels. The
      mean hs-CRP concentrations were associated with the mean total symptom score,
      independent of weight status (r = 0.56, P = 0.04). CONCLUSION: Healthy young
      women showed psychological and physical symptoms during the menstrual cycle which
      changed in association with alterations in low-grade inflammation and which were
      independent of body weight or plasma levels of gonadal steroids.

PMID- 16403013
TI  - The GYF domain.
AB  - GYF domains are small, versatile adaptor domains that recognize proline-rich
      sequences (PRS). They are present in most eukaryotic species sequenced so far,
      but in contrast to other PRS-recognition domains (PRD), GYF domains have not
      experienced the same amplification in metazoa during evolution. Mutational and
      structural analysis has shown the conserved signature W-X-Y-X(6-11)-GPF-X(4)-M
      X(2)-W-X(3)-GYF to be the site of interaction with proline-rich peptides. In
      contrast, composition and length of the C-terminal half of GYF domains are not
      conserved. Similar to other PRD, GYF domains bind to many different PRS that
      converge on a minimal consensus sequence. All GYF domains analyzed so far
      selected for the core motif PPG, whereas amino-acid preferences adjacent to this
      motif vary. As a result of this analysis, two subfamilies have been identified:
      CD2BP2-type and SMY2-type GYF domains. The latter subfamily comprises most GYF
      domains and is characterized by a shorter beta(1)-beta(2) loop and an aspartate
      instead of the tryptophan found at position 8 in CD2BP2-type GYF domains. Recent
      analysis of binding specificities for GYF domains allowed identification of novel
      interaction partners. Thereby proteomics has contributed to a functional
      understanding of GYF domain-containing proteins and sets the stage for a more
      systematic investigation of their functions in vivo.

PMID- 16403014
TI  - A tyrosinase with an abnormally high tyrosine hydroxylase/dopa oxidase ratio.
AB  - The sequencing of the genome of Ralstonia solanacearum[Salanoubat M, Genin S,
      Artiguenave F, et al. (2002) Nature 415, 497-502] revealed several genes that
      putatively code for polyphenol oxidases (PPOs). This soil-borne pathogenic
      bacterium withers a wide range of plants. We detected the expression of two PPO
      genes (accession numbers NP_518458 and NP_519622) with high similarity to
      tyrosinases, both containing the six conserved histidines required to bind the
      pair of type-3 copper ions at the active site. Generation of null mutants in
      those genes by homologous recombination mutagenesis and protein purification
      allowed us to correlate each gene with its enzymatic activity. In contrast with
      all tyrosinases so far studied, the enzyme NP_518458 shows higher monophenolase
      than o-diphenolase activity and its initial activity does not depend on the
      presence of l-dopa cofactor. On the other hand, protein NP_519622 is an enzyme
      with a clear preference to oxidize o-diphenols and only residual monophenolase
      activity, behaving as a catechol oxidase. These catalytic characteristics are
      discussed in relation to two other characteristics apart from the six conserved
      histidines. One is the putative presence of a seventh histidine which interacts
      with the carboxy group on the substrate and controls the preference for
      carboxylated and decarboxylated substrates. The second is the size of the residue
      isosteric with the aromatic F261 reported in sweet potato catechol oxidase which
      acts as a gate to control accessibility to CuA at the active site.

PMID- 16403015
TI  - Functional characterization of front-end desaturases from trypanosomatids depicts
      the first polyunsaturated fatty acid biosynthetic pathway from a parasitic
      protozoan.
AB  - A survey of the three kinetoplastid genome projects revealed the presence of
      three putative front-end desaturase genes in Leishmania major, one in Trypanosoma
      brucei and two highly identical ones (98%) in T. cruzi. The encoded gene products
      were tentatively annotated as Delta8, Delta5 and Delta6 desaturases for L. major,
      and Delta6 desaturase for both trypanosomes. After phylogenetic and structural
      analysis of the deduced proteins, we predicted that the putative Delta6
      desaturases could have Delta4 desaturase activity, based mainly on the conserved
      HX(3)HH motif for the second histidine box, when compared with Delta4 desaturases
      from Thraustochytrium, Euglena gracilis and the microalga, Pavlova lutheri, which
      are more than 30% identical to the trypanosomatid enzymes. After cloning and
      expression in Saccharomyces cerevisiae, it was possible to functionally
      characterize each of the front-end desaturases present in L. major and T. brucei.
      Our prediction about the presence of Delta4 desaturase activity in the three
      kinetoplastids was corroborated. In the same way, Delta5 desaturase activity was
      confirmed to be present in L. major. Interestingly, the putative Delta8
      desaturase turned out to be a functional Delta6 desaturase, being 35% and 31%
      identical to Rhizopus oryzae and Pythium irregulareDelta6 desaturases,
      respectively. Our results indicate that no conclusive predictions can be made
      about the function of this class of enzymes merely on the basis of sequence
      homology. Moreover, they indicate that a complete pathway for very-long-chain
      polyunsaturated fatty acid biosynthesis is functional in L. major using Delta6,
      Delta5 and Delta4 desaturases. In trypanosomes, only Delta4 desaturases are
      present. The putative algal origin of the pathway in kinetoplastids is discussed.

PMID- 16403016
TI  - Computer-assisted mass spectrometric analysis of naturally occurring and
      artificially introduced cross-links in proteins and protein complexes.
AB  - A versatile software tool, VIRTUALMSLAB, is presented that can perform advanced
      complex virtual proteomic experiments with mass spectrometric analyses to assist
      in the characterization of proteins. The virtual experimental results allow
      rapid, flexible and convenient exploration of sample preparation strategies and
      are used to generate MS reference databases that can be matched with the real MS
      data obtained from the equivalent real experiments. Matches between virtual and
      acquired data reveal the identity and nature of reaction products that may lead
      to characterization of post-translational modification patterns, disulfide bond
      structures, and cross-linking in proteins or protein complexes. The most
      important unique feature of this program is the ability to perform multistage
      experiments in any user-defined order, thus allowing the researcher to vary
      experimental approaches that can be conducted in the laboratory. Several features
      of VIRTUALMSLAB are demonstrated by mapping both disulfide bonds and artificially
      introduced protein cross-links. It is shown that chemical cleavage at aspartate
      residues in the protease resistant RNase A, followed by tryptic digestion can be
      optimized so that the rigid protein breaks up into MALDI-MS detectable fragments,
      leaving the disulfide bonds intact. We also show the mapping of a number of
      chemically introduced cross-links in the NK1 domain of hepatocyte growth
      factor/scatter factor. The VIRTUALMSLAB program was used to explore the
      limitation and potential of mass spectrometry for cross-link studies of more
      complex biological assemblies, showing the value of high performance instruments
      such as a Fourier transform mass spectrometer. The program is freely available
      upon request.

PMID- 16403017
TI  - Peroxisome proliferator-activated receptor alpha plays a vital role in inducing a
      detoxification system against plant compounds with crosstalk with other
      xenobiotic nuclear receptors.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is thought to play
      an important role in lipid metabolism in the liver. To clarify the extra-hepatic
      and/or unknown function of PPARalpha, we previously performed a proteome analysis
      of the intestinal proteins and identified 17beta-hydroxysteroid dehydrogenase
      type 11 as a mostly induced protein by a PPARalpha ligand [Motojima, K. (2004)
      Eur. J. Biochem. 271, 4141-4146]. Because of its supposed wide substrate
      specificity, we examined the possibility that PPARalpha plays an important role
      in inducing detoxification systems for some natural foods by feeding mice with
      various plant seeds and grains. Feeding with sesame but not others often killed
      PPARalpha knockout mice but not wild-type mice. A microarray analysis of the
      sesame-induced mRNAs in the intestine revealed that PPARalpha plays a vital role
      in inducing various xenobiotic metabolizing enzymes in the mouse intestine and
      liver. A PPARalpha ligand alone could not induce most of these enzymes,
      suggesting that there is an essential crosstalk among PPARalpha and other
      xenobiotic nuclear receptors to induce a detoxification system for plant
      compounds.

PMID- 16403018
TI  - Recognition of DNA modified by trans-[PtClNH(4-hydroxymethylpyridine)] by tumor
      suppressor protein p53 and character of DNA adducts of this cytotoxic complex.
AB  - trans-[PtCl(2)NH(3)(4-Hydroxymethylpyridine)] (trans-PtHMP) is an analogue of
      clinically ineffective transplatin, which is cytotoxic in the human leukemia
      cancer cell line. As DNA is a major pharmacological target of antitumor platinum
      compounds, modifications of DNA by trans-PtHMP and recognition of these
      modifications by active tumor suppressor protein p53 were studied in cell-free
      media using the methods of molecular biology and biophysics. Our results
      demonstrate that the replacement of the NH(3) group in transplatin by the 4
      hydroxymethylpyridine ligand affects the character of DNA adducts of parent
      transplatin. The binding of trans-PtHMP is slower, although equally sequence
      specific. This platinum complex also forms on double-stranded DNA stable
      intrastrand and interstrand cross-links, which distort DNA conformation in a
      unique way. The most pronounced conformational alterations are associated with a
      local DNA unwinding, which was considerably higher than those produced by other
      bifunctional platinum compounds. DNA adducts of trans-PtHMP also reduce the
      affinity of the p53 protein to its consensus DNA sequence. Thus, downstream
      effects modulated by recognition and binding of p53 protein to DNA distorted by
      trans-PtHMP and transplatin are not likely to be the same. It has been suggested
      that these different effects may contribute to different antitumor effects of
      these two transplatinum compounds.

PMID- 16403019
TI  - The monopartite nuclear localization signal of autoimmune regulator mediates its
      nuclear import and interaction with multiple importin alpha molecules.
AB  - Autoimmune regulator (AIRE) is a transcriptional regulator involved in
      establishing immunological self-tolerance. Mutations in the AIRE gene lead to the
      development of the autosomal, recessively inherited, organ-specific autoimmune
      disease, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED).
      The AIRE protein is mainly localized in the cell nucleus where it is associated
      with nuclear bodies. The N-terminal part of AIRE has been previously shown to
      mediate nuclear localization of the protein. However, the functional nuclear
      localization signal (NLS) and nuclear import mechanisms of AIRE have not been
      identified. We show that, although the amino-acid sequence of AIRE contains a
      potential bipartite NLS consisting of amino acids 110-114 and 131-133, only the
      latter part constitutes a functional NLS. Furthermore, we show by in vitro
      binding assays that AIRE interacts with multiple members of the nuclear transport
      receptor importin alpha family, mainly alpha1, alpha3, and alpha5, and that these
      interactions depend on the intactness of the Arg-Lys-rich NLS of AIRE. In
      addition, we found that AIRE binds to the 'minor' NLS-binding site of importin
      alpha3 and alpha5 proteins consisting of the C-terminal armadillo repeats 7-9.
      Our findings strongly suggest that the nuclear import of AIRE is mediated by the
      classical importin alpha/beta pathway through binding to several importin alpha
      family members.

PMID- 16403021
TI  - The role of glucose 6-phosphate in mediating the effects of glucokinase
      overexpression on hepatic glucose metabolism.
AB  - Pharmacological activation or overexpression of glucokinase in hepatocytes
      stimulates glucose phosphorylation, glycolysis and glycogen synthesis. We used an
      inhibitor of glucose 6-phosphate (Glc6P) hydrolysis, namely the chlorogenic
      derivative, 1-[2-(4-chloro-phenyl)-cyclopropylmethoxy]-3, 4-dihydroxy-5-(3
      imidazo[4,5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexanecarboxylic acid (also
      known as S4048), to determine the contribution of Glc6P concentration, as
      distinct from glucokinase protein or activity, to the control of glycolysis and
      glycogen synthesis by glucokinase overexpression. The validity of S4048 for
      testing the role of Glc6P was supported by its lack of effect on glucokinase
      binding and its nuclear/cytoplasmic distribution. The stimulation of glycolysis
      by glucokinase overexpression correlated strongly with glucose phosphorylation,
      whereas glycogen synthesis correlated strongly with Glc6P concentration.
      Metabolic control analysis was used to determine the sensitivity of glycogenic
      flux to glucokinase or Glc6P at varying glucose concentrations (5-20 mm). The
      concentration control coefficient of glucokinase on Glc6P (1.4-1.7) was
      relatively independent of glucose concentration, whereas the flux control
      coefficients of Glc6P (2.4-1.0) and glucokinase (3.7-1.8) on glycogen synthesis
      decreased with glucose concentration. The high sensitivity of glycogenic flux to
      Glc6P at low glucose concentration is consistent with covalent modification by
      Glc6P of both phosphorylase and glycogen synthase. The high control strength of
      glucokinase on glycogenic flux is explained by its concentration control
      coefficient on Glc6P and the high control strength of Glc6P on glycogen
      synthesis. It is suggested that the regulatory strength of pharmacological
      glucokinase activators on glycogen metabolism can be predicted from their effect
      on the Glc6P content.

PMID- 16403020
TI  - Systemic RNAi of the cockroach vitellogenin receptor results in a phenotype
      similar to that of the Drosophila yolkless mutant.
AB  - During vitellogenesis, one of the most tightly regulated processes in oviparous
      reproduction, vitellogenins are incorporated into the oocyte through vitellogenin
      receptor (VgR)-mediated endocytosis. In this paper, we report the cloning of the
      VgR cDNA from Blattella germanica, as well as the first functional analysis of
      VgR following an RNA interference (RNAi) approach. We characterized the VgR, VgR
      mRNA and protein expression patterns in pre-adult and adult stages of this
      cockroach, as well as VgR immunolocalization in ovarioles, belonging to the
      panoistic type. We then specifically disrupted VgR gene function using RNAi
      techniques. Knockdown of VgR expression led to a phenotype characterized by low
      yolk content in the ovary and high vitellogenin concentration in the haemolymph.
      This phenotype is equivalent to that of the yolkless mutant of Drosophila
      melanogaster, which have the yl (VgR) gene disrupted. The results additionally
      open the perspective that development genes can be functionally analyzed via
      systemic RNAi in this basal species.

PMID- 16403022
TI  - Repeats of LacdiNAc and fucosylated LacdiNAc on N-glycans of the human parasite
      Schistosoma mansoni.
AB  - N-Glycans from glycoproteins of the worm stage of the human parasite Schistosoma
      mansoni were enzymatically released, fluorescently labelled and analysed using
      various mass spectrometric and chromatographic methods. A family of 28 mainly
      core-alpha1-6-fucosylated, diantennary N-glycans of composition Hex(3-4)HexNAc(6
      12)Fuc(1-6) was found to carry dimers of N,N'-diacetyllactosediamine [LacdiNAc or
      LDN; GalNAc(beta1-4)GlcNAc(beta1-] with or without fucose alpha1-3-linked to the
      N-acetylglucosamine residues in the antennae {GalNAc(beta1-4)[+/-Fuc(alpha1
      3)]GlcNAc(beta1-3)GalNAc(beta1-4)[+/-Fuc(alpha1-3)]GlcNAc(beta1-}. To date,
      oligomeric LDN and oligomeric fucosylated LDN (LDNF) have been found only on N
      glycans from mammalian cells engineered to express Caenorhabditis elegansbeta4
      GalNAc transferase and human alpha3-fucosyltransferase IX [Z. S. Kawar et al.
      (2005) J Biol Chem280, 12810-12819]. It now appears that LDN(F) repeats can also
      occur in a natural system such as the schistosome parasite. Like monomeric LDN
      and LDNF, the dimeric LDN(F) moieties found here are expected to be targets of
      humoral and cellular immune responses during schistosome infection.

PMID- 16403023
TI  - Structural diversity of angiotensin-converting enzyme.
AB  - The crystal structure of a Drosophila angiotensin-converting enzyme (ANCE) has
      recently been solved, revealing features important for the binding of ACE
      inhibitors and allowing molecular comparisons with the structure of human
      testicular angiotensin-converting enzyme (tACE). ACER is a second Drosophila ACE
      that displays both common and distinctive properties. Here we report further
      functional differences between ANCE and ACER and have constructed a homology
      model of ACER to help explain these. The model predicts a lack of the Cl(-)
      binding sites, and therefore the strong activation of ACER activity towards
      enkephalinamide peptides by NaCl suggests alternative sites for Cl(-) binding.
      There is a marked difference in the electrostatic charge of the substrate channel
      between ANCE and ACER, which may explain why the electropositive peptide,
      MKRSRGPSPRR, is cleaved efficiently by ANCE with a low K(m), but does not bind to
      ACER. Bradykinin (BK) peptides are excellent ANCE substrates. Models of BK docked
      in the substrate channel suggest that the peptide adopts an N-terminal beta-turn,
      permitting a tight fit of the peptide in the substrate channel. This, together
      with ionic interactions between the guanidino group of Arg9 of BK and the side
      chains of Asp360 and Glu150 in the S(2)' pocket, are possible reasons for the
      high-affinity binding of BK. The replacement of Asp360 with a histidine in ACER
      would explain the higher K(m) recorded for the hydrolysis of BK peptides by this
      enzyme. Other differences in the S(2)' site of ANCE and ACER also explain the
      selectivity of RXPA380, a selective inhibitor of human C-domain ACE, which also
      preferentially inhibits ACER. These structural and enzymatic studies provide
      insight into the molecular basis for the distinctive enzymatic features of ANCE
      and ACER.

PMID- 16403024
TI  - Factor VIIIa regulates substrate delivery to the intrinsic factor X-activating
      complex.
AB  - Activation of coagulation factor X (fX) by activated factors IX (fIXa) and VIII
      (fVIIIa) requires the assembly of the enzyme-cofactor-substrate fIXa-fVIIIa-fX
      complex on negatively charged phospholipid membranes. Using flow cytometry, we
      explored formation of the intermediate membrane-bound binary complexes of fIXa,
      fVIIIa, and fX. Studies of the coordinate binding of coagulation factors to 0.8
      microm phospholipid vesicles (25/75 phosphatidylserine/phosphatidylcholine)
      showed that fVIII (fVIIIa), fIXa, and fX bind to 32 700 +/- 5000 (33 200 +/- 14
      100), 20 000 +/- 4500, and 30 500 +/- 1300 binding sites per vesicle with
      apparent K(d) values of 76 +/- 23 (71 +/- 5), 1510 +/- 430, and 223 +/- 79 nm,
      respectively. FVIII at 10 nm induced the appearance of additional high-affinity
      sites for fIXa (1810 +/- 370, 20 +/- 5 nm) and fX (12 630 +/- 690, 14 +/- 4 nm),
      whereas fX at 100 nm induced high-affinity sites for fIXa (541 +/- 67, 23 +/- 5
      nm). The effects of fVIII and fVIIIa on the binding of fIXa or fX were similar.
      The apparent Michaelis constant of the fX activation by fIXa was a linear
      function of the fVIIIa concentration with a slope of 1.00 +/- 0.12 and an
      intrinsic K(m) value of 8.0 +/- 1.5 nm, in agreement with the hypothesis that the
      reaction rate is limited by the fVIIIa-fX complex formation. In addition, direct
      correlation was observed between the fX activation rate and formation of the
      fVIIIa-fX complex. Titration of fX, fVIIIa, phospholipid concentration and
      phosphatidylserine content suggested that at high fVIIIa concentration the
      reaction rate is regulated by the concentration of free fX rather than of
      membrane-bound fX. The obtained results reveal formation of high-affinity fVIIIa
      fX complexes on phospholipid membranes and suggest their role in regulating fX
      activation by anchoring and delivering fX to the enzymatic complex.

PMID- 16403025
TI  - Structural characterization of the large soluble oligomers of the GTPase effector
      domain of dynamin.
AB  - Dynamin, a protein playing crucial roles in endocytosis, oligomerizes to form
      spirals around the necks of incipient vesicles and helps their scission from
      membranes. This oligomerization is known to be mediated by the GTPase effector
      domain (GED). Here we have characterized the structural features of recombinant
      GED using a variety of biophysical methods. Gel filtration and dynamic light
      scattering experiments indicate that in solution, the GED has an intrinsic
      tendency to oligomerize. It forms large soluble oligomers (molecular mass > 600
      kDa). Interestingly, they exist in equilibrium with the monomer, the equilibrium
      being largely in favour of the oligomers. This equilibrium, observed for the
      first time for GED, may have regulatory implications for dynamin function. From
      the circular dichroism measurements the multimers are seen to have a high helical
      content. From multidimensional NMR analysis we have determined that about 30
      residues in the monomeric units constituting the oligomers are flexible, and
      these include a 17 residue stretch near the N-terminal. This contains two short
      segments with helical propensities in an otherwise dynamic structure. Negatively
      charged SDS micelles cause dissociation of the oligomers into monomers, and
      interestingly, the helical characteristics of the oligomer are completely
      retained in the individual monomers. The segments along the chain that are likely
      to form helices have been predicted from five different algorithms, all of which
      identify two long stretches. Surface electrostatic potential calculation for
      these helices reveals that there is a distribution of neutral, positive and
      negative potentials, suggesting that both electrostatic and hydrophobic
      interactions could be playing important roles in the oligomer core formation. A
      single point mutation, I697A, in one of the helices inhibited oligomerization
      quite substantially, indicating firstly, a special role of this residue, and
      secondly, a decisive, though localized, contribution of hydrophobic interaction
      in the association process.

PMID- 16403026
TI  - Human-blind probes and primers for dengue virus identification.
AB  - Reliable detection and identification of pathogens in complex biological samples,
      in the presence of contaminating DNA from a variety of sources, is an important
      and challenging diagnostic problem for the development of field tests. The
      problem is compounded by the difficulty of finding a single, unique genomic
      sequence that is present simultaneously in all genomes of a species of closely
      related pathogens and absent in the genomes of the host or the organisms that
      contribute to the sample background. Here we describe 'host-blind probe design'-
      a novel strategy of designing probes based on highly frequent genomic signatures
      found in the pathogen genomes of interest but absent from the host genome. Upon
      hybridization, an array of such informative probes will produce a unique pattern
      that is a genetic fingerprint for each pathogen strain. This multiprobe approach
      was applied to 83 dengue virus genome sequences, available in public databases,
      to design and perform in silico microarray experiments. The resulting patterns
      allow one to unequivocally distinguish the four major serotypes, and within each
      serotype to identify the most similar strain among those that have been
      completely sequenced. In an environment where dengue is indigenous, this would
      allow investigators to determine if a particular isolate belongs to an ongoing
      outbreak or is a previously circulating version. Using our probe set, the
      probability that misdiagnosis at the serotype level would occur is approximately
      1 : 10(150).

PMID- 16403027
TI  - Inhibition of aryl acid adenylation domains involved in bacterial siderophore
      synthesis.
AB  - Aryl acid adenylation domains are the initial enzymes for aryl-capping of
      catecholic siderophores in a plethora of microorganisms. In order to overcome the
      problem of iron acquisition in host organisms, siderophore biosynthesis is
      decisive for virulence development in numerous important human and animal
      pathogens. Recently, it was shown that growth of Mycobacterium tuberculosis and
      Yersinia pestis can be inhibited in an iron-dependent manner using the arylic
      acyl adenylate analogue 5'-O-[N-(salicyl)-sulfamoyl] adenosine that acts on the
      salicylate activating domains, MbtA and YbtE [Ferreras JA, Ryu JS, Di Lello F,
      Tan DS, Quadri LEN (2005) Nat Chem Biol1, 29-32]. The present study explores the
      behaviour of the 2,3-dihydroxybenzoate activating domain DhbE (bacillibactin
      synthesis) and compares it to that of YbtE (yersiniabactin synthesis) upon
      enzymatic inhibition using a set of newly synthesized aryl sulfamoyl adenosine
      derivatives. The obtained results underline the highly specific mode of
      inhibition for both aryl acid activating domains in accordance with their
      natively accepted aryl moiety. These findings are discussed regarding the
      structure-function based aspect of aryl substrate binding to the DhbE and YbtE
      active sites.

PMID- 16403028
TI  - Stage-specific expression of Caenorhabditis elegans ribonuclease H1 enzymes with
      different substrate specificities and bivalent cation requirements.
AB  - Ribonuclease H1 (RNase H1) is a widespread enzyme found in a range of organisms
      from viruses to humans. It is capable of degrading the RNA moiety of DNA-RNA
      hybrids and requires a bivalent ion for activity. In contrast with most
      eukaryotes, which have one gene encoding RNase H1, the activity of which depends
      on Mg(2+) ions, Caenorhabditis elegans has four RNase H1-related genes, and one
      of them has an isoform produced by alternative splicing. However, little is known
      about the enzymatic features of the proteins encoded by these genes. To determine
      the differences between these enzymes, we compared the expression patterns of
      each RNase H1-related gene throughout the development of the nematode and the
      RNase H activities of their recombinant proteins. We found gene-specific
      expression patterns and different enzymatic features. In particular, besides the
      enzyme that displays the highest activity in the presence of Mg(2+) ions, C.
      elegans has another enzyme that shows preference for Mn(2+) ion as a cofactor. We
      characterized this Mn(2+)-dependent RNase H1 for the first time in eukaryotes.
      These results suggest that there are at least two types of RNase H1 in C. elegans
      depending on the developmental stage of the organism.

PMID- 16403031
TI  - Research on mental health literacy: what we know and what we still need to know.

PMID- 16403032
TI  - Mental health first aid training: review of evaluation studies.
AB  - OBJECTIVE: To review studies evaluating mental health first aid (MHFA) training.
      METHOD: Review of three published trials: one uncontrolled with members of the
      public in a city, one randomized controlled efficacy trial in a workplace setting
      and one cluster randomized effectiveness trial with the public in a rural area.
      RESULTS: Most mental health first aiders tend to be middle-aged women whose work
      involves people contact. All trials found the following statistically significant
      benefits 5-6 months post-training: improved concordance with health professionals
      about treatments, improved helping behaviour, greater confidence in providing
      help to others and decreased social distance from people with mental disorders.
      Only one trial evaluated the mental health benefits to participants and this
      found positive effects. CONCLUSIONS: Although MHFA training has been found to
      change knowledge, attitudes and helping behaviours, and even benefit the mental
      health of participants, there has not yet been an evaluation of the effects on
      those who are the recipients of the first aid.

PMID- 16403033
TI  - Cognitive behavioural therapy for depression, panic disorder and generalized
      anxiety disorder: a meta-regression of factors that may predict outcome.
AB  - OBJECTIVE: To determine which factors impact on the efficacy of cognitive
      behavioural therapy (CBT) for depression and anxiety. Factors considered include
      those related to clinical practice: disorder, treatment type, duration and
      intensity of treatment, mode of therapy, type and training of therapist and
      severity of patients. Factors related to the conduct of the trial were also
      considered, including: year of study, country of study, type of control group,
      language, number of patients and percentage of dropouts from the trial. METHOD:
      We used the technique of meta-analysis to determine an overall effect size
      (standardized mean difference calculated using Hedges' g) and meta-regression to
      determine the factors that impact on this effect size. We included randomized
      controlled trials with a wait list, pill placebo or attention/psychological
      placebo control group. Study participants had to be 18 years or older and all
      have diagnosed depression, panic disorder (with or without agoraphobia) or
      generalized anxiety disorder (GAD). Outcomes of interest included symptom,
      functioning and health-related quality of life measures, reported as continuous
      variables at post-treatment. RESULTS: Cognitive behavioural therapy for
      depression, panic disorder and GAD had an effect size of 0.68 (95% CI=0.51-0.84,
      n=33 studies, 52 comparisons). The heterogeneity in the effect sizes was fully
      explained by treatment, duration of therapy, inclusion of severe patients in the
      trial, year of study, country of study, control group, language and number of
      dropouts from the control group. Disorder was not a significant predictor of the
      effect size. CONCLUSIONS: Cognitive behavioural therapy is significantly less
      effective for severe patients and trials that compared CBT to a wait-list control
      group found significantly larger effect sizes than those comparing CBT to an
      attention placebo, but not to a pill placebo. Further research is needed to
      determine whether CBT is effective when provided by others than psychologists and
      whether it is effective for non-English-speaking patient groups.

PMID- 16403034
TI  - The nonlinear theory of schizophrenia.
AB  - OBJECTIVE: Nonlinear properties exist within the brain across a hierarchy of
      scales and within a variety of critical neural processes. Only a few studies of
      brain activity in schizophrenia, however, have used nonlinear methods. This
      review paper evaluates the contribution of the nonlinear sciences towards
      understanding schizophrenia. METHOD: Applications of nonlinear methods to the
      study of schizophrenia symptoms and to healthy and schizophrenia functional
      neuroscience data are reviewed. The main flaws of nonlinear algorithms and recent
      methods to correct these are also appraised. RESULTS: Initial research methods
      utilized in the study of nonlinearity in schizophrenia have fundamental
      methodological limitations. In the last decade, many of these problems have been
      addressed, facilitating future progress. Research incorporating these
      improvements has been applied to normal electroencephalogram (EEG) data and to
      the symptoms of schizophrenia, but not systematically to brain imaging data
      collected from patients with schizophrenia. CONCLUSION: There is strong
      statistical evidence for weak nonlinearity in normal EEG and in the fluctuations
      of the symptoms of schizophrenia. However, the contribution of nonlinear
      processes to brain dysfunction in schizophrenia is yet to be properly established
      or accurately quantified. Despite this, recent methodological advances suggest
      that a 'nonlinear theory' of schizophrenia may be helpful in understanding this
      disorder.

PMID- 16403035
TI  - The public's ability to recognize mental disorders and their beliefs about
      treatment: changes in Australia over 8 years.
AB  - OBJECTIVE: A national survey of Australian adults in 1995 showed a low level of
      recognition of mental disorders and beliefs about treatment that were often
      discordant with those of professionals. The present study aimed to find out
      whether recognition and treatment beliefs have changed over 8 years. METHOD: A
      national survey of 2001 adults in 2003-2004 included the same questions as the
      1995 survey. These interview questions were based on a vignette of a person with
      either depression or schizophrenia. RESULTS: Over the 8 years, the public showed
      better recognition of depression and schizophrenia and gave more positive ratings
      to a range of interventions, including help from mental health professionals,
      medications, psychotherapy and psychiatric ward admission. CONCLUSIONS: The
      Australian public's beliefs have changed over 8 years to be more like those of
      mental health professionals. This change may have positive implications for help
      seeking and treatment concordance.

PMID- 16403036
TI  - Changes in depression awareness and attitudes in Australia: the impact of
      beyondblue: the national depression initiative.
AB  - OBJECTIVE: To assess changes in depression awareness and attitudes in Australia
      and the effect that beyondblue: the national depression initiative has had on
      these. METHOD: Data from national surveys of mental health literacy in 1995 and
      2003-2004 were analysed to see if states and territories that funded beyondblue
      (the high-exposure states) had greater changes than those that did not (the low
      exposure states). In both surveys, participants were shown a depression vignette
      and asked whether they themselves or family or friends had ever had a similar
      problem, whether they thought the person would be discriminated against, and
      questions about the likelihood of long-term positive and negative outcomes for
      the person. Participants were also assessed for symptoms of psychological
      distress in the past month. RESULTS: There was an increase in the percentage of
      people who said that they or their family or friends had a problem like the
      person in the vignette. This increase was greater in the high-exposure states.
      However, there was no change in reports of current psychological distress,
      suggesting that there is greater depression awareness or openness rather than a
      real increase in symptoms. People in the high-exposure states also showed an
      increase in the belief that discrimination would occur. There was little change
      in beliefs about long-term outcomes, apart from people in high-exposure states
      believing that a depressed person would be more understanding of other people's
      feelings. CONCLUSIONS: The data are consistent with beyondblue having had an
      effect on awareness of depression and of discrimination against depressed people.

PMID- 16403037
TI  - Changes in psychological distress in Australia over an 8-year period: evidence
      for worsening in young men.
AB  - OBJECTIVE: To assess whether psychological distress has changed in the Australian
      population. METHOD: Data were obtained from national household surveys of 1964
      Australian adults in 1995 and 3507 in 2003-2004. Psychological distress was
      measured using the 4-NS, which asks about symptoms of depression, anxiety,
      irritability and nervousness in the past month. The data were analysed by gender
      and by age group, from 20-24 years to 70-74 years. RESULTS: Psychological
      distress was found to have increased in men aged 20-29 years. This change was
      observed even when the same cohorts were compared. No change was found in women
      or in other male age groups. CONCLUSIONS: These data show the need for routine
      population monitoring of mental health to determine subgroups requiring priority
      action.

PMID- 16403038
TI  - Stigma about depression and its impact on help-seeking intentions.
AB  - OBJECTIVE: Research has shown that people are reluctant to seek professional help
      for depression, especially from mental health professionals. This may be because
      of the impact of stigma which can involve people's own responses to depression
      and help-seeking (self stigma) as well as their perceptions of others' negative
      responses (perceived stigma). The aim of this article was to examine community
      help-seeking intentions and stigmatizing beliefs associated with depression.
      METHOD: A total of 1,312 adults randomly sampled from the Australian community
      completed a questionnaire providing a depression vignette and measures of self-
      and perceived-stigmatizing responses, source-specific help-seeking intentions,
      current depressive symptoms and depression experience, and demographics. RESULTS:
      Many people reported they would feel embarrassed about seeking help from
      professionals, and believed that other people would have a negative reaction to
      them if they sought such help. Some expected professionals to respond negatively
      to them. Responses varied according to the sources of professional help. Self
      embarrassment and expectations that others would respond negatively predicted the
      likelihood of help-seeking from professional sources. CONCLUSION: Self- and
      perceived-stigmatizing responses to help-seeking for depression are prevalent in
      the community and are associated with reluctance to seek professional help.
      Interventions should focus on minimizing expectations of negative responses from
      others and negative self-responses to help-seeking, and should target younger
      people.

PMID- 16403039
TI  - Positive relationships between public awareness activity and recognition of the
      impacts of depression in Australia.
AB  - OBJECTIVE: This report records the level of exposure to depression-related
      information across the Australian community and explores associations with
      recognition of depression and relevant sociodemographic factors. METHOD: A cross
      sectional telephone survey was conducted with a representative community sample.
      Participants consisted of 3200 respondents (400 respondents across each
      Australian State/Territory). RESULTS: Sixty-five point four per cent
      (n=2089/3193) of respondents indicated that they or someone close to them had
      experienced depression, of whom 18.7% (n=391/2089) reported a personal experience
      of this illness. Various measures of recent exposure to depression-related
      information were high with 69.0% (n=2207/3200) reporting that they had seen, read
      or heard something in the media in the last 12 months. Recognition of beyondblue:
      the national depression initiative was also surprisingly high (61.9%, 1982/3200).
      Those with greater understanding that depression is common and debilitating were
      more likely to recall recent media stories, spontaneously recall relevant
      organizations such as beyondblue, to have had direct or family experiences, to be
      younger and to have achieved higher levels of education. Depression, however, is
      rarely mentioned (1.3%, 47/3720) as a major general health as distinct from a
      mental health problem. CONCLUSION: The active promotion of depression-related
      material to the community appears to have contributed to recognition of the
      commonality and impacts of this illness. Although depression is commonly
      recognized as a mental health problem, it is not yet considered a major general
      health problem. Further, like many public health campaigns, those initially
      reached appear more likely to be female, younger, better educated and residing in
      metropolitan areas.

PMID- 16403040
TI  - Free range users and one hit wonders: community users of an Internet-based
      cognitive behaviour therapy program.
AB  - OBJECTIVE: Little is known about the predictors of symptom change or the methods
      that might increase user 'compliance' on websites designed to improve mental
      health outcomes. The present paper: (i) examines predictors of expected final
      depression and anxiety scores on the MoodGYM website as a function of user
      characteristics; and (ii) compares the compliance rates of the original site with
      the new public version of the site (MoodGYM Mark II). The latter site requires
      compulsory completion of 'core' online assessments and may increase completion of
      site questionnaires. METHOD: MoodGYM Mark I participants were 19,607 visitors
      (public registrants) between April 2001 and September 2003 plus 182 participants
      who had been randomly assigned to MoodGYM in an earlier trial (The BlueMood
      Trial). MoodGYM Mark II participants were 38,791 public registrants of the
      MoodGYM Mark II site collected between September 2003 and October 2004. Symptom
      assessments are repeated within the website intervention to allow the examination
      of change in symptoms. Outcome variables were gender, initial depression severity
      scores, number of assessments completed and final anxiety and depression scores.
      RESULTS: Men are predicted to be 0.19 units (SE=0.095) higher than women on
      depression, controlling for the initial depression level and number of modules
      completed. For initial depression scores above 2, it is predicted that the final
      score will indicate improvement relative to the initial score, the magnitude of
      the improvement increasing as a function of the number of modules attempted. For
      initial anxiety scores above 2, it is predicted that the final score will
      indicate improvement relative to the initial score, the magnitude of the
      improvement increasing as a function of the number of modules attempted. Mark II
      registrants were more likely than to Mark I registrants to complete onsite
      assessments. CONCLUSIONS: Visitors to the MoodGYM site are likely to have better
      psychological outcomes if they complete more of the site material. Compulsory
      completion of core sections increases assessment completion. There is a need to
      examine further the significance of attrition from online interventions, to
      develop methods of handling missing data, and to investigate strategies to
      improve visitor dropout.

PMID- 16403041
TI  - Adolescents' responses to peers with depression or conduct disorder.
AB  - OBJECTIVE: To determine how young people are likely to respond to a peer with
      mental illness, or who has severe behavioural problems. METHOD: A mental health
      literacy survey was conducted with 1137 adolescents in years 8, 9 and 10 in South
      Australia and the Australian Capital Territory. Respondents were presented with a
      vignette of either a 16-year-old boy meeting criteria for conduct disorder or a
      16-year-old girl meeting criteria for major depression. As part of the survey,
      respondents were asked to write in words what they would do if the person in the
      vignette was a friend of theirs and they wished to help. Responses were coded
      into categories. RESULTS: Over half the sample (53%) described positive social
      support as the only action they would take to help. A further 23% said they would
      engage an adult such as a parent, teacher or school counsellor to help with the
      situation. Those responding to the conduct disorder vignette were more likely to
      describe engaging an adult to help and males were more likely to say they would
      do nothing. Female students tended to answer differently to the conduct disorder
      and depression vignettes, while male students responded similarly to the two
      vignettes. CONCLUSIONS: Many adolescents do not respond to friends' distress in
      ways which are likely to facilitate appropriate help. Mental health education in
      schools should include skills for offering help and encouraging peers to seek
      help.

PMID- 16403042
TI  - Comorbid behavioural problems in Tourette's syndrome are positively correlated
      with the severity of tic symptoms.
AB  - OBJECTIVE: We studied the comorbid behavioural and mood problems in children with
      non-psychiatric Tourette's syndrome (TS) and their relationship with severity of
      tic disorder. METHOD: Sixty-nine TS children and 69 healthy controls were
      assessed by Child Behavior Checklist (CBCL) and Yale Global Tic Severity Scale
      (YGTSS). The relationships between behavioural problems and severity of tic
      symptoms were analysed statistically by comparison, correlation and multiple
      linear regression. RESULTS: Tourette's syndrome patients scored significantly
      lower (p<0.01) on the CBCL competency subscales and total score, and higher on
      all behavioural problem subscales and total score (p<0.01). Expectedly, the TS
      children had lower social competence than normal children. Among the TS children,
      the severity of tic symptoms is positively correlated with the severity of
      overall impairment in school and social competence. When the behavioural and mood
      problems commonly associated with TS were studied in detail, we found that
      delinquent behaviour, thought problems, attention problems, aggressive behaviour
      and externalizing are positively correlated with severity of tic symptoms.
      CONCLUSION: The findings indicated that children with TS-only also had a broad
      range of behavioural problems, and some of these were related to the severity of
      tic symptoms.

PMID- 16403043
TI  - Who treats whom? An application of the Pathways to Care model in Australia.
AB  - OBJECTIVE: The present paper applies Goldberg and Huxley's Pathways to Care (PTC)
      model to the Australian health-care system to ask: who is treated in each sector
      and what does this tell us about the performance of the health-care system? It
      examines the factors associated with reaching primary care, outpatient and
      inpatient sectors, as well as private and public mental health services. METHOD:
      Data from the Australian National Survey of Mental Health and Wellbeing were used
      to determine the proportion of the population treated in each sector.
      Sociodemographic and clinical characteristics were examined and logistic
      regression was used to determine which factors were associated with use of
      different sectors of care. RESULTS: Of the total population, 80.5% reached
      primary care, 8.2% primary care for mental health problems, 6.5% outpatient care
      and 0.4% reached the mental health inpatient sector. Clinical severity increased
      across these sectors and was an important determinant of access to care. Those
      consulting private practitioners were clinically similar to those consulting in
      the public sector. Sociodemographic characteristics were important determinants
      of access to primary, specialist and private mental health care. Being aged over
      55 years or living in a rural area was associated with lower access to several
      sectors. CONCLUSIONS: Although at a broad level the health-care system is
      performing as expected, limited access among some groups is cause for concern.
      Applying the PTC model to a population sample offered useful insights into the
      performance of the Australian health-care system.

PMID- 16403044
TI  - Risk and protective factors for medically serious suicide attempts: a comparison
      of hospital-based with population-based samples of young adults.
AB  - OBJECTIVE: To investigate risk and protective factors for medically serious
      suicide attempts among young Australian adults. METHOD: The study used a case
      control design. A clinical sample of 18-24 year olds was recruited via the
      emergency department of a large public hospital following a suicide attempt
      (n=95) and was compared to a sample of 18-24 year olds who participated in a
      population-based survey (n=380). RESULTS: Risk factors for medically serious
      suicide attempts included early school leaving, parental divorce (males only),
      distress due to problems with parents (females only), distress due to problems
      with friends, distress due to the break-up of a romantic relationship, tobacco
      use, high alcohol use, current depressive symptomatology and a previous diagnosis
      of depression. Protective factors included social connectedness, problem-solving
      confidence and locus of control. There was a trend for social connectedness to be
      more protective among those with high rather than low levels of depressive
      symptomatology, and among smokers rather than non-smokers. CONCLUSIONS: Results
      are discussed in terms of designing evidence-based suicide prevention activities
      for young adults.

PMID- 16403045
TI  - Popper versus Freud.

PMID- 16403046
TI  - Clozapine and heart in the Hunter region.

PMID- 16403048
TI  - Outcome study tools and clinical practice.

PMID- 16403053
TI  - Clinical course and implantable cardioverter defibrillator therapy in
      postinfarction women with severe left ventricular dysfunction.
AB  - BACKGROUND: There are limited data regarding implantable cardioverter
      defibrillator (ICD) therapy in postinfarction women with severe left ventricular
      dysfunction. The aim of this study was to evaluate the risk of cardiac events and
      effects of ICD therapy in women as compared to men enrolled in the Multicenter
      Automatic Defibrillator Implantation Trial II (MADIT II). METHODS AND RESULTS:
      Among 1,232 patients enrolled in MADIT II, there were 192 (16%) women and 1,040
      (84%) men. When compared to men, women had an increased frequency of NYHA class >
      or =II (70 vs 63%; P = 0.067), hypertension (60% vs 52%; P = 0.047), diabetes
      (42% vs 34%; P = 0.027), and LBBB (25% vs 17%; P = 0.011), and less frequent CABG
      surgery (42% vs 60%; P < 0.001). The 2-year cumulative mortality in patients
      randomized to conventional therapy was not significantly different in women and
      men (30% and 20%, respectively; P = 0.19). Adjusting for relevant clinical
      covariates, the hazard ratios for ICD effectiveness were similar in women (0.57;
      95% CI = 0.28-1.18; P = 0.132) and men (0.66; 95% CI = 0.48-0.91; P = 0.011). The
      risk of appropriate ICD therapy for VT/VF was lower in women than in men (hazard
      ratio = 0.60 for female vs male gender; 95% CI = 0.37-0.98; P = 0.039).
      CONCLUSIONS: MADIT II women had similar mortality and similar ICD effectiveness
      when compared to men. MADIT II women with ICDs had a lower risk of arrhythmic
      events with fewer episodes of ventricular tachycardia than men.

PMID- 16403054
TI  - Does ICD therapy benefit women with a history of myocardial infarction and severe
      left ventricular dysfunction?

PMID- 16403055
TI  - Hemodynamic effects of atrial septal pacing in cardiac resynchronization therapy
      patients.
AB  - INTRODUCTION: Spontaneous or pacing-induced interatrial conduction delay may
      affect the outcome of heart failure patients treated with cardiac
      resynchronization therapy (CRT). The objective of this study was to evaluate the
      impact of the atrial pacing site (right atrial appendage, RAA; and low
      interatrial septum, LIS) during biventricular (BV) pacing on the left ventricular
      (LV) systolic function in candidates for CRT. METHODS AND RESULTS: Fifteen heart
      failure patients with left bundle branch block and LV ejection fraction < or =35%
      were enrolled. Electrodes were placed at the RAA, LIS, right ventricular apex,
      and LV free wall. A DDD protocol was tested, which consisted of 50 beats in AAI
      mode from the RAA followed by 50 beats in BV DDD mode with atrial pacing at the
      RAA (DDD_RAA) or at the LIS (DDD_LIS) at four AV delays. The average (+/
      SD)%LV+dP/dtmax increase during DDD_RAA and DDD_LIS pacing with respect to
      baseline was 24 +/- 16% and 21 +/- 15%, respectively (P < 0.01), and average
      percentage change in aortic pulse pressure during DDD_RAA and DDD_LIS with
      respect to baseline (%PP) was 13 +/- 8% and 13 +/- 7% (ns). CONCLUSIONS: Our
      results show a significant hemodynamic improvement with both DDD_RAA and DDD_LIS
      biventricular pacing compared to AAI pacing. However DDD_LIS pacing was not
      superior to DDD_RAA pacing in acute hemodynamic responses.

PMID- 16403056
TI  - Delayed defibrillation testing in patients implanted with biventricular ICD (CRT
      D): a reliable and safe approach.
AB  - BACKGROUND: Defibrillation testing (DT) at the end of the implantation of cardiac
      resynchronization pacemaker with a defibrillator (CRT-D) exposes heart failure
      (HF) patients to increased procedural risks. However, until now, delayed DT has
      not been assessed as a possible option in HF patients implanted with CRT-D.
      OBJECTIVE: Aim of the present study is to assess safety and feasibility of
      delayed DT in HF patients treated with CRT-D. MATERIAL AND METHODS: Two hundred
      and eleven consecutive patients (mean age: 65 years, mean NYHA class 3.0, mean
      EF: 29.3%) underwent CRT-D implantation from October 1999 to December 2004. In
      the first 17 patients, DT was performed at the end of CRT-D implantation. In the
      other 194 consecutive patients, DT was performed at 2 months after CRT-D
      implantation. Outcome of DT, as well as "acute" LV lead dislodgment rate were
      evaluated in the latter group of 194 patients undergoing a delayed DT. Also, ICD
      function was assessed through device telemetry analysis at 2 months. RESULTS: At
      delayed DT, first shock was effective in 187 of 194 patients (96%), ineffective
      VF interruption at maximum energy occurred only in one patient (0.5%), and acute
      LV lead dislodgment was 1%. No ICD therapy failure occurred in the 2-month
      untested period. CONCLUSION: DT performed 2 months after CRT-D implantation is
      safe and feasible; this is possibly related to the improvement of clinical
      conditions and hemodynamic status as well as greater lead stability 2 months
      after CRT-D.

PMID- 16403057
TI  - Delayed defibrillation testing after CRT-D implant-weighing competing risks.

PMID- 16403058
TI  - Value of different follow-up strategies to assess the efficacy of circumferential
      pulmonary vein ablation for the curative treatment of atrial fibrillation.
AB  - BACKGROUND: The objective of this study was to compare transtelephonic ECG every
      2 days and serial 7-day Holter as two methods of follow-up after atrial
      fibrillation (AF) catheter ablation for the judgment of ablation success.
      Patients with highly symptomatic AF are increasingly treated with catheter
      ablation. Several methods of follow-up have been described, and judgment on
      ablation success often relies on patients' symptoms. However, the optimal follow
      up strategy objectively detecting most of the AF recurrences is yet unclear.
      METHODS: Thirty patients with highly symptomatic AF were selected for
      circumferential pulmonary vein ablation. During follow-up, a transtelephonic ECG
      was transmitted once every 2 days for half a year. Additionally, a 7-day Holter
      was recorded preablation, after ablation, after 3 and 6 months, respectively.
      With both, procedures symptoms and actual rhythm were correlated thoroughly.
      RESULTS: A total of 2,600 transtelephonic ECGs were collected with 216 of them
      showing AF. 25% of those episodes were asymptomatic. On a Kaplan-Meier analysis
      45% of the patients with paroxysmal AF were still in continuous SR after 6
      months. Simulating a follow-up based on symptomatic recurrences only, that number
      would have increased to 70%. Using serial 7-day ECG, 113 Holter with over 18,900
      hours of ECG recording were acquired. After 6 months the percentage of patients
      classified as free from AF was 50%. Of the patients with recurrences, 30-40% were
      completely asymptomatic. The percentage of asymptomatic AF episodes stepwise
      increased from 11% prior ablation to 53% 6 months after. CONCLUSIONS: The success
      rate in terms of freedom from AF was 70% on a symptom-only-based follow-up; using
      serial 7-day Holter it decreased to 50% and on transtelephonic monitoring to 45%,
      respectively. Transtelephonic ECG and serial 7-day Holter were equally effective
      to objectively determine long-term success and to detect asymptomatic patients.

PMID- 16403059
TI  - Comparison between anatomical and integrated approaches to atrial fibrillation
      ablation: adjunctive role of electrical pulmonary vein disconnection.
AB  - INTRODUCTION: The aim of this study was to compare the outcome of anatomical
      pulmonary vein (PV) radiofrequency (RF) ablation with that of an integrated
      approach (anatomical with electrophysiological confirmation of PV disconnection).
      METHODS: Sixty consecutive patients affected by drug-refractory paroxysmal (39),
      persistent (13), and permanent (8) atrial fibrillation (AF) were assigned to an
      anatomical (group A: 30 patients; 25 male, 5 female, mean age: 55 +/- 7 years) or
      integrated approach (group B: 30 patients; 26 male, 4 female, mean age: 52 +/- 9
      years). In all cases, RF ablation was performed by means of the Carto system in
      order to anatomically create circumferential lines around PVs. In group B, the
      persistence of PV potentials was then assessed with a multipolar circular
      catheter. If PV potentials persisted, RF pulses targeting the
      electrophysiological breakthroughs were delivered to disconnect PVs. RESULTS:
      Total procedure duration, fluoroscopy time, and RF delivery time were similar in
      both groups: 227 +/- 43, 50 +/- 23, and 43 +/- 16 minutes (group A); 232 +/- 32,
      55 +/- 15, and 42 +/- 10 minutes (group B), respectively (ns). One asymptomatic
      PV stenosis and one pericardial effusion occurred in group A and B, respectively.
      After 15.4 +/- 7.4 months, 17 (57%) group A patients and 25 (83%) group B
      patients were in stable sinus rhythm (P = 0.02) (RR 1.78; 95% CI: 1.7-2.9).
      CONCLUSIONS: PV ablation by means of an integrated anatomical and
      electrophysiological approach seems more effective than a purely anatomical RF
      ablation approach. Electrophysiological confirmation of PV disconnection could be
      a useful marker of successful RF treatment of AF.

PMID- 16403060
TI  - Clinical predictors of noninducibility of sustained atrial fibrillation after
      pulmonary vein isolation.
AB  - BACKGROUND: Noninducibility of sustained atrial fibrillation (AF) after pulmonary
      vein isolation (PVI) has been shown to be associated with a better clinical
      outcome. We evaluated the role of clinical variables that could predict
      noninducibility of sustained AF after PVI. METHODS AND RESULTS: Data were
      collected prospectively from 181 patients (153 male; age 54 +/- 9 years) referred
      for ablation of drug-refractory symptomatic paroxysmal AF (duration < or =7
      days). Clinical variables were evaluated with regard to their ability of
      predicting noninducibility of sustained AF (< or =10 minutes) after PVI.
      Univariate analysis was performed on all collected variables followed by
      multivariate analysis for variables showing a P value <0.1. After PVI, sustained
      AF was noninducible in 97 (54%) patients. The following clinical variables showed
      a significant difference between the groups: body weight, longest AF episode,
      duration of AF history, presence or absence of structural heart disease, left
      ventricular (LV) hypertrophy, prior cardioversion, left atrial (LA) parasternal,
      and longitudinal diameters and LV diameters. On multivariate analysis, three
      independent predictors of noninducibility were identified: a shorter duration of
      AF episodes (AF <12 hours: RR 0.01 (0.002-0.06), P < 0.001; AF 12-48 hours: RR
      0.07 (0.01-0.37), P = 0.001); LA longitudinal diameter <57 mm (RR 0.33 (0.13
      0.82), P = 0.016); and absence of LV hypertrophy (RR 0.15 (0.04-0.63), P = 0.01).
      CONCLUSIONS: Shorter AF episodes, smaller LA longitudinal diameter, and absence
      of LV hypertrophy are independent predictors of noninducibility of sustained AF
      after PVI.

PMID- 16403061
TI  - Isolation of pulmonary veins using a transvenous curvilinear cryoablation
      catheter: feasibility, initial experience, and analysis of recurrences.
AB  - INTRODUCTION: Pulmonary vein isolation (PVI) using focal cryothermal catheters is
      safe and moderately effective, but associated with long procedure times. We
      hypothesized that a linear freezing segment could shorten fluoroscopic and
      procedure times. We report our initial experience with a novel circular
      cryothermal catheter. METHODS AND RESULTS: Complete PV isolation (PVI) was
      achieved in 41 of 45 PVs by cryoablation (91%) in 18 patients who underwent Lasso
      guided cryothermal using a novel 7 F circular catheter (2.5 +/- 0.7 veins per
      patient). A mean of 27.2 +/- 11 applications per patient (9.2 +/- 4.7 per vein)
      with a mean temperature -79.8 +/- 4 degrees C were delivered. Recorded
      temperatures did not predict complete or incomplete isolation. Focal cryothermal
      ablation using a 7 F 4-mm tip was required in the remainder for isolation. During
      14.8 +/- 6.2 month follow-up, 4 (22%) had no recurrence of AF, and 7/18 (39%) had
      >90% reduction in symptoms without antiarrhythmic agents (AAA). Computed
      tomography scans at 3 months showed no stenosis (14.1 +/- 2.5 mm, 13.9 +/- 2.4
      mm; P = 0.2). Eight patients underwent repeat ablation. Mapping demonstrated 13
      of 14 (93%) previously isolated veins had recovery of over 64 +/- 24% of the
      ostium. All were successfully isolated with RF and 7 of 8 were arrhythmia free
      6.0 +/- 2.9 months after ablation. Overall, 14 of 18 (78%) patients had their
      arrhythmia clinically controlled without drugs after one or two procedures.
      CONCLUSIONS: Our initial experience demonstrates safety and feasibility of
      circular cryothermal ablation with less fluoroscopic and procedure times as
      compared to focal cryothermy. As with RF, complete and permanent isolation of the
      PVs is not easily achieved. Reducing heat load due to PV flow may improve
      results.

PMID- 16403062
TI  - Cryoablation of atrial fibrillation: getting warmer?

PMID- 16403063
TI  - Relationship between dominant prolongation of the filtered QRS duration in the
      right precordial leads and clinical characteristics in Brugada syndrome.
AB  - BACKGROUND: Electrical abnormalities in the RVOT may be involved in Brugada
      syndrome. OBJECTIVES: We investigated the relationship between the signal
      averaged ECG (SAECG) and electrophysiologic study (EPS), especially focusing on
      conduction delay in the outflow tract of the right ventricle (RVOT) and its
      contribution to clinical characteristics. METHODS: Twenty-four patients with
      Brugada syndrome (23 men and 1 woman; 61 +/- 16 years old) were studied. We
      assessed the presence of late potential (LP) in SAECG and the filtered QRS
      duration in the right precordial leads (V1 or V2; RfQRS) and in the left
      precordial leads (V5 or V6; LfQRS) and the difference between them. In 18
      patients, SAECG was evaluated for an LP on three separate occasions. RESULTS:
      SAECG was positive for LP in 15 patients at least once; and in 7 patients, SAECG
      was positive for an LP on multiple occasions, and 6 of 7 patients (86%) had a
      history of cardiac arrest. The difference between RfQRS and LfQRS was
      significantly greater in patients with cardiac arrest than in patients with
      syncope or in asymptomatic patients; 29 +/- 10, 14 +/- 11 (P < 0.01), and 7 +/- 5
      msec (P < 0.001), respectively. All patients were alive and one patient with
      cardiac arrest had an appropriate VF therapy delivered by the ICD. CONCLUSIONS:
      The dominant prolongation of the filtered QRS duration in the right precordial
      leads may be related to the risk of arrhythmic event in Brugada syndrome.

PMID- 16403064
TI  - Mechanisms of phrenic nerve injury during radiofrequency ablation at the
      pulmonary vein orifice.
AB  - BACKGROUND: The phrenic nerve can be injured with radiofrequency energy delivery.
      Nevertheless, the mechanisms of injury are unknown. This study was undertaken to
      examine phrenic nerve tissue temperatures during ablation at the pulmonary vein
      (PV) orifice, assess the temperature dependence of injury, and to delineate the
      possible mechanisms of untoward nerve effects. METHODS: Ten dogs underwent
      ablation at the right superior PV (RSPV) orifice. Phrenic nerve temperatures were
      assessed with implanted thermocouples overlying the endocardial ablation site.
      Using an 8-mm ablation catheter tip, energy was titrated to 50 degrees C and
      incremented by 5 degrees C for 120 seconds. RESULTS: Phrenic nerve capture was
      achieved in nine (90%) dogs after thermocouple implantation. A RSPV orifice
      tissue temperature >60 degrees C occurred in 32 (84%) of energy deliveries with a
      power of 34 +/- 22 W. In three (33%) dogs, this resulted in nerve dysfunction
      (maximum nerve temperature: 41 degrees C, 41 degrees C, and 91 degrees C) with
      histology consistent with acute thermal injury. In four additional dogs, 17
      energy deliveries were made directly to the phrenic nerve using a novel in situ
      model. In 5 (29%) energy deliveries, nerve function was impacted immediately by
      the generated current, with resolution simultaneous with discontinuing
      radiofrequency. Transient phrenic nerve injury occurred in all dogs at a
      temperature of 47 +/- 3 degrees C (range: 43-53 degrees C) after 38 +/- 32
      seconds (range: 20-120 seconds). After termination of the energy delivery, nerve
      function returned in 15(88%) during 30 seconds of postablation pacing. In two
      (12%) ablation attempts, nerve recovery was delayed (>3 minutes). Permanent
      injury occurred in all dogs after 92 +/- 83 seconds (range: 20-280 seconds) of
      additional energy delivery at a temperature of 51 +/- 6 degrees C (range: 45-65
      degrees C). CONCLUSION: Phrenic nerve injury can be more common than anticipated
      with RF ablation at the RSPV orifice. Relatively low tissue temperatures can
      injure the nerve. Immediate nerve effects suggest a second mechanism of nerve
      dysfunction related to electrical current. Transient nerve effects occur prior to
      permanent damage, providing an opportunity to discontinue energy delivery before
      permanent injury.

PMID- 16403065
TI  - Phrenic nerve injury-yet another Achilles' heel for AF ablation?

PMID- 16403066
TI  - Paced electrogram fractionation analysis of arrhythmogenic tendency in DeltaKPQ
      Scn5a mice.
AB  - INTRODUCTION: Gain-of-function mutations within Scn5a, including the DeltaKPQ
      1505-1507 deletion in the inactivation domain compromising myocardial
      repolarization, are implicated in human long QT 3 syndrome (LQT3), associated
      with ventricular arrhythmogenesis and sudden death. METHODS AND RESULTS: Patch
      clamp studies on isolated ventricular Scn5a+/Delta myocytes from DeltaKPQ mice
      produced by homologous recombination in embryonic stem (ES) cells confirmed such
      altered electrophysiological properties of the mutant channel. Programmed
      electrical stimulation (PES) with decremental pacing from the basal right
      ventricular epicardial surface and paced electrogram fractionation analysis
      (PEFA) of electrograms recorded from the basal left ventricular epicardial
      surface of Langendorff-perfused whole heart preparations demonstrated ventricular
      tachycardia (VT) in 8 of 9 Scn5a+/Delta mutant (but no Scn5a+/+ (wild-type (WT))
      controls; n = 17), with increased electrogram durations (EGD) and more dispersed
      conduction curves. Isoproterenol (100 nM) was without effect on tachycardic
      Scn5a+/Delta hearts (n = 9) yet propranolol (1 microM) prevented VT in all
      isoproterenol-infused WT control (n = 4) but no Scn5a+/Delta hearts (n = 4).
      Furthermore propranolol itself increased EGD and dispersion in Scn5a+/Delta
      hearts. In contrast, mexiletine (10 microM) suppressed VTs in 4 of 5 Scn5a+/Delta
      hearts without altering EGD or dispersion. CONCLUSION: Beta-adrenoreceptor
      blockade does not confer an antiarrhythmic effect and may even enhance
      arrhythmogenesis by increasing reentrant substrate in Scn5a+/Delta hearts while
      mexiletine protects against VT without modifying conduction characteristics.
      Together these findings permit a scheme where VT in LQT3 is initiated by
      triggered mechanisms but propagated by reentry.

PMID- 16403067
TI  - Atrial natriuretic peptide has dose-dependent, autonomically mediated effects on
      atrial refractoriness and repolarization in anesthetized dogs.
AB  - INTRODUCTION: Atrial natriuretic peptide (ANP) may alter electrophysiological
      properties of the heart and possibly have a role in arrhythmogenesis. However,
      previous studies have yielded conflicting results and have not fully considered
      whether ANP's cardiac electrophysiological effects are mediated via direct
      actions and/or indirectly via the autonomic nervous system. This study's aim was
      to establish whether ANP infused at pathophysiological and pharmacological doses
      has significant in vivo cardiac electrophysiological effects and to determine
      whether these effects are directly or autonomically mediated. METHODS AND
      RESULTS: Electrophysiologic and hemodynamic effects of ANP infusion (human ANP at
      15-600 ng/kg per minute) were examined in chloralose-anesthetized dogs under
      conditions of varying autonomic blockade. In autonomically intact dogs (n = 12),
      low-dose ANP (15 ng/kg per minute) shortened atrial effective refractory period
      (ERP) (P < 0.001) and monophasic action potential duration (MAPD90) (P < 0.05) at
      600, 500, and 400 msec atrial paced cycle lengths and reduced right atrial
      pressure (P < 0.05) but did not alter mean arterial pressure. After either
      combined vagal and beta-adrenergic blockade (vagotomy plus atropine plus
      propranolol, n = 7) or selective vagal blockade (n = 9), low-dose ANP no longer
      altered atrial ERP or MAPD90. Higher ANP doses (150 and 600 ng/kg per minute)
      decreased mean arterial and right atrial pressures (P < 0.001) but did not alter
      atrial ERP, MAPD90, or other electrophysiological parameters including atrial
      fibrillation threshold, ventricular ERP, and MAPD90. CONCLUSION: ANP has dose
      dependent, autonomically mediated effects on atrial refractoriness and
      repolarization.

PMID- 16403068
TI  - Mapping of atrial activation during sustained atrial fibrillation in dogs with
      rapid ventricular pacing induced heart failure: evidence for a role of driver
      regions.
AB  - INTRODUCTION: Dogs with rapid ventricular pacing (RVP)-induced congestive heart
      failure (CHF) have inducible atrial tachycardia, flutter, and fibrillation (AF).
      We tested the hypothesis that rapid atrial activation in multiple regions and at
      different rates is responsible for sustained AF in this CHF model. METHODS AND
      RESULTS: We studied 12 episodes of sustained (>10 minutes) AF induced in 12 dogs
      with CHF produced by 3-6 weeks of RVP at 230 beats/minute. High-density mapping
      of AF was performed using 382 unipolar atrial electrograms recorded
      simultaneously from epicardial electrodes on the right (RA) and left atria (LA)
      and Bachmann's bundle. AF mechanisms were based on Fast Fourier Transform (FFT)
      analysis and activation sequence mapping. A driver was defined as a rapid stable
      activation region with a single dominant frequency peak in FFT analysis. During
      AF, three FFT and activation patterns were seen: (1) a single LA driver (7.8 +/-
      1.1 Hz) near the pulmonary veins (PVs) with irregular activation in the rest of
      the atria (n = 4); (2) simultaneous, multisite, biatrial drivers at differing
      frequencies (LA vs RA dominant frequency gradient: 1.3 +/- 0.8 Hz) near the PVs
      (8.4 +/- 0.3 Hz) and high RA (8.5 +/- 1.5 Hz) (n = 7); and (3) biatrial irregular
      activation with multiple and/or broadband frequency peaks without a dominant
      frequency. (LA: 7.1-11.4 Hz; RA: 5.9-7.7 Hz) (n = 1). Atrial drivers had either a
      focal activation pattern or were due to a macroreentrant circuit around the PVs.
      CONCLUSIONS: In this CHF model, FFT analysis and activation sequence mapping
      demonstrate that sustained AF is characterized by single and multiple, stable LA
      and RA drivers with predominant sources in the PVs and high RA causing
      fibrillatory conduction.

PMID- 16403069
TI  - Driver regions in atrial fibrillation associated with congestive heart failure:
      where are they, and what are they telling us?

PMID- 16403070
TI  - Determinants and effects of electrical stimulation of the inferior interatrial
      parasympathetic plexus during atrial fibrillation.
AB  - INTRODUCTION: Catheter stimulation of the inferior interatrial ganglionated
      parasympathetic plexus decreases the ventricular rate during atrial fibrillation
      (AF) in humans. However, the relatively high stimulation voltages might prevent
      implementation of neurostimulation in chronic implantable devices. From
      myocardial electrostimulation it is known that the required impulse energy and
      charge is lowest at the chronaxie time. In order to lower energy requirements for
      cardiac neurostimulation, the present study evaluates the impulse-strength versus
      impulse-duration relationship for a neurostimulation lead that was implanted into
      the inferior interatrial ganglionated plexus. METHODS AND RESULTS: In nine dogs,
      permanent epicardial bipolar screw-in electrodes were fixed in the inferior
      interatrial ganglionated plexus. AF was maintained via rapid atrial pacing.
      During AF, neural stimulation was performed at various frequencies (1-100 Hz),
      impulse durations (0.05-2 msec), and voltages (0.02-11.5 V). There was a linear
      correlation between R-R interval lengthening and stimulus voltage (R = 0.99; P <
      0.001) and a bell-shaped relationship between stimulation frequency and negative
      dromotropic effect with maximum rate slowing at 30-50 Hz. The rheobase for a 50%
      R-R interval prolongation during AF was 1.81 V and 2.72 V for high-grade AVB
      yielding a chronaxie time of 0.14 msec and 0.18 msec, respectively. The impulse
      energy (charge) at the chronaxie time was 4-6 microJ (6-8 microC). CONCLUSIONS:
      Cardiac neurostimulation follows a chronaxie/rheobase behavior. Energy, charge,
      and voltage values needed to achieve significant negative dromotropic effects are
      within the limits of conventional cardiac pacemaker outputs, which may allow
      implementation of neurostimulation capabilities in current pacemaker technology.

PMID- 16403071
TI  - From selective parasympathetic modulation of AV node to rate control therapy.

PMID- 16403072
TI  - Curative therapy for swallowing-induced tachycardia by pulmonary vein antrum
      isolation.
AB  - We present a case of a 49-year-old man who experienced invariably reproducible
      paroxysmal supraventricular tachycardia during swallowing. Because beta-blockers
      and multiple antiarrhythmic drugs failed to prevent the episodes of this
      tachycardia, we performed catheter mapping and ablation. After placing multiple
      decapolar catheters, when the patient swallowed a few sections of an orange,
      intracardiac mapping revealed atrial premature beats and atrial tachycardia that
      lasted for a few seconds and arose from an ostial site of the right superior
      pulmonary vein. After the right superior pulmonary vein antrum was completely
      isolated, the patient became free from the swallowing-induced tachycardia.

PMID- 16403073
TI  - Ketoconazole induced torsades de pointes without concomitant use of QT interval
      prolonging drug.
AB  - Ketoconazole is not known to be proarrhythmic without concomitant use of QT
      interval-prolonging drugs. We report a woman with coronary artery disease who
      developed a markedly prolonged QT interval and torsades de pointes (TdP) after
      taking ketoconazole for treatment of fungal infection. Her QT interval returned
      to normal upon withdrawal of ketoconazole. Genetic study did not find any
      mutation in her genes that encode cardiac IKr channel proteins. We postulate that
      by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT
      interval and induce TdP. This calls for attention when ketoconazole is
      administered to patients with risk factors for acquired long QT syndrome.

PMID- 16403074
TI  - Successful radiofrequency catheter ablation of epicardial left ventricular
      outflow tract tachycardia from the anterior interventricular coronary vein.
AB  - We report a case of idiopathic left ventricular outflow tract (LVOT) tachycardia
      that was eliminated by a radiofrequency application from the anterior
      interventricular coronary vein (AIV). The ECG exhibited QRS complexes with an
      inferior axis and atypical left bundle branch block pattern with an early
      transition of the precordial R waves at V3. Several radiofrequency applications
      from the coronary cusps and endocardial LVOT were not effective. Radiofrequency
      applications in the AIV, where the activation preceded the onset of the QRS by 30
      msec, successfully eliminated the tachycardia. The AIV may be an optional site
      for radiofrequency ablation of idiopathic epicardial LVOT tachycardia.

PMID- 16403075
TI  - Endocardial implantation of a cardioverter defibrillator in early childhood.
AB  - INTRODUCTION: Experience in endovascular/endocardial techniques for implanting
      implantable cardioverter defibrillators in early childhood is limited.
      Potentially, this type of approach could limit the surgical risk, while
      increasing ICD therapy efficacy. The safety and feasibility of adopting a
      complete endovascular/endocardial approach for implanting ICDs is assessed by
      considering the cases of two young children. METHODS AND RESULTS: Two boys, aged
      3 and 6 years, were implanted with ICD for a history of syncope and documented
      ventricular tachycardia (VT). A complete endovascular/endocardial approach was
      adopted consisting of positioning a bipolar pacing and sensing lead in the right
      ventricular (RV) apex with intravascular redundancy forming a loop in the
      inferior vena cava (IVC), and a caval coil placed in the IVC. Sensing values (7-8
      mV), pacing threshold (0.5-0.6 V/0.5 msec), and defibrillation testing (case 1 =
      10 J, case 2 = 20 J) were all acceptable. During follow-up, in both cases ICD
      intervened correctly. In one case, 16 months after implantation, because of
      change in the IVC coil-active can vector, the IVC coil was effectively
      repositioned to a more distal position. CONCLUSION: A complete
      endovascular/endocardial ICD implantation technique in early childhood is both
      feasible and safe. This approach avoids thoracotomy and ensures ICD therapy
      efficacy.

PMID- 16403076
TI  - "Pseudosinus rhythm": what is the mechanism?

PMID- 16403077
TI  - Pause before you pace.

PMID- 16403078
TI  - The adenosine triphospate (ATP) test for evaluation of syncope of unknown origin.

PMID- 16403079
TI  - Right top pulmonary vein anomaly.

PMID- 16403080
TI  - Localization of left atrial esophageal anatomical relationship using CT-fluoro
      registration.

PMID- 16403081
TI  - The mechanism of sudden death in the Wolff-Parkinson-White syndrome.

PMID- 16403082
TI  - Complete heart block induced and terminated by a premature contraction.

PMID- 16403084
TI  - Gold-tip electrodes--a new 'deep lesion' technology for catheter ablation? In
      vitro comparison of gold alloy versus platinum-iridium tip electrode ablation
      catheter.

PMID- 16403085
TI  - Tachycardia with VA dissociation: an unusual tachycardia mechanism.

PMID- 16403087
TI  - Nurse-led care in dermatology: a review of the literature.
AB  - BACKGROUND: Nurses play lead roles in the delivery of care in dermatology. While
      a number of primary studies have been conducted evaluating nurse-led care in
      dermatology, review and synthesis of the findings from these studies has not been
      undertaken. OBJECTIVES: To systematically identify, summarize and critically
      appraise the current evidence regarding the impact and effectiveness of nurse-led
      care in dermatology. METHODS: Systematic searches were done of CINAHL, MEDLINE,
      British Nursing Index and the Royal College of Nursing Library Catalogue from
      1990 until March 2005. The searches were not restricted to the U.K., and were
      supplemented by an extensive hand search of the literature through references
      identified from retrieved articles and by contact with experts in the field.
      RESULTS: A total of 14 relevant publications were identified (and included
      findings from both primary and secondary care), of which five were descriptions
      of nursing activities, five were evaluations of nurse interventions and four were
      patient evaluations of nurse-led care. The evidence emerging from the literature
      indicates that nurses are treating a number of dermatological conditions,
      primarily using treatment protocols, across a broad range of clinical settings.
      However, there is a lack of confidence among nurses working in primary care
      (predominantly practice nurses) to treat some of these conditions (including
      scalp scaling in psoriasis and infected eczema). Although the importance of
      education is recognized, the educational needs of these nurses are frequently
      unmet. The benefits of nurse interventions on service delivery include a
      reduction in the severity of condition and more effective use of topical
      therapies. Patients report faster access to treatment, a reduction in referrals
      to the GP or dermatologist, and an increase in knowledge of their condition.
      CONCLUSIONS: Nurses frequently play lead roles in the diverse range of models of
      care that exist in dermatology. Although findings of the review are generally
      positive, there are methodological weaknesses and under-researched issues, e.g.
      cost effectiveness of nurse-led care, and extended independent and supplementary
      nurse prescribing in dermatology, that point to the need for further rigorous
      evaluation.

PMID- 16403088
TI  - Evidence-based practice of photopheresis 1987-2001: a report of a workshop of the
      British Photodermatology Group and the U.K. Skin Lymphoma Group.
AB  - Photopheresis or extracorporeal photochemotherapy (ECP) is a novel
      immunomodulatory therapy which involves separation of the patient's leucocyte
      rich plasma, followed by ex vivo administration of a photosensitizer and
      ultraviolet A radiation, before reinfusion. ECP has been used successfully for
      the treatment of cutaneous T-cell lymphoma (CTCL: Sezary syndrome), graft-versus
      host disease (GVHD) and cardiac transplant rejection. ECP has a dose-sparing
      effect on concurrent immunosuppressive therapy. The procedure induces apoptosis
      of the irradiated lymphocytes, but the exact mechanism by which ECP exerts its
      therapeutic effect in these different conditions is uncertain. The treatment has
      very few adverse effects and in particular is not associated with an increased
      incidence of opportunistic infections. The evidence for the efficacy of ECP has
      been appraised by a combined British Photodermatology Group and U.K. Skin
      Lymphoma Group workshop on the basis of evidence published up to the end of 2001
      and on the consensus of best practice. There is fair evidence for the use of ECP
      in erythrodermic CTCL and steroid-refractory GVHD, but randomized controlled
      studies are needed. There is good evidence supporting the use of ECP in
      preventing cardiac rejection following transplantation. Randomized controlled
      trials have also shown a therapeutic benefit in type 1 diabetes mellitus, but the
      inconvenience associated with the procedure outweighed the clinical benefit.
      There is fair evidence not to use ECP for the treatment of systemic sclerosis and
      multiple sclerosis, and good evidence not to use ECP for other forms of CTCL.

PMID- 16403089
TI  - Gender differences and effects of sex steroids and dehydroepiandrosterone on
      androgen and oestrogen alpha receptors in mouse sebaceous glands.
AB  - BACKGROUND: It is generally believed that the sebaceous gland is an intracrine
      organ which synthesizes its own active hormones to meet its local needs.
      OBJECTIVES: To understand further the mechanisms of sex steroid action in mouse
      sebaceous glands. METHODS: We have used immunocytochemistry to examine the
      expression of oestrogen receptor alpha (ERalpha) and androgen receptor (AR) in
      mouse sebaceous glands. RESULTS: In intact males AR is exclusively localized in
      the nuclei of basal and mature sebocytes, while in females it is present at a
      lower level in both the nuclei and the cytoplasm. Three weeks following
      gonadectomy (GDX), a marked decrease of AR labelling is observed in male
      sebocytes, while no change occurs in female sebocytes. Treatment of GDX animals
      with dihydrotestosterone (DHT) or dehydroepiandrosterone (DHEA) increases AR
      expression, while 17beta-estradiol (E2) decreases the stimulatory effect of DHT
      and DHEA. ERalpha is detected only in basal sebocytes of intact females but not
      in males. Following treatment with E2, ERalpha expression becomes visible in GDX
      males while DHT and DHEA inhibit the effect of E2. CONCLUSIONS: The present data
      show gender differences and demonstrate that DHT, E2 and DHEA exert specific
      effects on the expression of AR and ERalpha in mouse sebocytes.

PMID- 16403090
TI  - Induction of scratching behaviour and dermatitis in various strains of mice
      cohabiting with NC/Nga mice with chronic dermatitis.
AB  - BACKGROUND: NC/Nga (NC) mice with similar pathological and behavioural features
      as seen in human atopic dermatitis are used as a model of the disease. Under
      normal circumstances, spontaneous and persistent scratching occurs in NC mice and
      this can lead to the onset of skin inflammation. OBJECTIVES: We examined the
      induction of scratching behaviour in NC, BALB/c, ICR and C3H/HeN mice, and of
      dermatitis in NC and BALB/c mice, by cohabitation with mice with dermatitis.
      METHODS: NC, BALB/c, ICR and C3H/HeN mice were kept together with NC mice with
      chronic dermatitis (CNV-NC) for 2 weeks, and the numbers of scratching episodes
      were counted. NC and BALB/c mice were also kept together with CNV-NC mice for 24
      weeks and the skin severity score was assessed. The score was assessed for a
      further 8 weeks after separation of these mice. RESULTS: The number of scratching
      episodes in NC, BALB/c, ICR and C3H/HeN mice was increased by cohabitation with
      CNV-NC mice. Cohabitation with CNV-NC mice led to dermatitis in both NC and
      BALB/c mice. The number of scratching episodes and the skin severity score in
      BALB/c mice were about half of those in NC mice. When cohabitation with CNV-NC
      mice stopped, the number of scratching episodes and the skin severity score
      decreased in BALB/c mice, but not in NC mice. Changes in the histopathological
      data of BALB/c mice supported the severity of skin inflammation. CONCLUSIONS: Our
      study demonstrates that scratching behaviour and dermatitis can be induced in
      various strains of mice by cohabitation with CNV-NC mice, and that cessation of
      cohabitation leads to a recovery in BALB/c mice but not in NC mice.

PMID- 16403091
TI  - Granulocyte/macrophage colony-stimulating factor treatment of human chronic
      ulcers promotes angiogenesis associated with de novo vascular endothelial growth
      factor transcription in the ulcer bed.
AB  - Summary Background Granulocyte/macrophage colony-stimulating factor (GM-CSF), a
      cytokine with pleiotropic functions, has been successfully employed in the
      treatment of chronic skin ulcers. The biological effects underlying GM-CSF action
      in impaired wound healing have been only partly clarified. Objectives To
      investigate the effects of GM-CSF treatment of chronic venous ulcers on lesion
      vascularization and on the local synthesis of the angiogenic factors vascular
      endothelial growth factor (VEGF) and placenta growth factor (PlGF). Methods
      Patients with nonhealing venous leg ulcers were treated with intradermal
      injection of recombinant human GM-CSF, and biopsies were taken at the ulcer
      margin before and 5 days after administration. Wound vascularization was analysed
      by immunohistochemistry using antiplatelet endothelial cell adhesion molecule
      1/CD31 and anti-alpha-smooth muscle actin antibodies. VEGF and PlGF transcription
      was assessed by in situ hybridization. To identify the cell populations
      transcribing VEGF within the ulcer bed, the VEGF hybridization signal was
      correlated with the immunostaining for different cell type markers on serial
      sections. Direct induction of VEGF transcription by GM-CSF was investigated in GM
      CSF-treated cultured macrophages and keratinocytes. Results Blood vessel density
      was significantly increased in the ulcer bed following GM-CSF treatment. VEGF
      transcripts were localized in keratinocytes at the ulcer margin both before and
      after GM-CSF treatment, whereas a VEGF hybridization signal was evident within
      the ulcer bed only following administration. PlGF mRNA was barely detectable in
      keratinocytes at the ulcer margin and was not visibly increased after treatment.
      Unlike VEGF, a specific PlGF hybridization signal could not be detected in cells
      within the ulcer following GM-CSF administration. Monocytes/macrophages were the
      main cell population transcribing VEGF after GM-CSF treatment. In vitro analysis
      demonstrated that VEGF transcription can be directly stimulated by GM-CSF in a
      differentiated monocytic cell line, but not in keratinocytes. Conclusions Our
      data show that increased vascularization is associated with GM-CSF treatment of
      chronic venous ulcers and indicate that inflammatory cell-derived VEGF may act as
      an angiogenic mediator of the healing effect of GM-CSF in chronic ulcers.

PMID- 16403092
TI  - Epithelial regeneration from bioengineered skin explants in culture.
AB  - BACKGROUND: Artificial skin substitutes are beneficial in the treatment of
      chronic wounds although their performance relative to authentic human skin is
      unclear. OBJECTIVES: We compared the rate of outgrowth and morphology of
      neoepidermis from a bioengineered skin construct (Apligraf) with normal adult
      human skin explants on de-epidermized human dermal growth substrate with or
      without intact epidermal basement membrane zone. METHODS: Epithelial outgrowth of
      air-exposed cultures in serum-supplemented keratinocyte medium was quantified by
      fluorescence imaging, morphology by light microscopy, biomarkers of keratinocyte
      activation, proliferation and migration by immunohistochemical analysis, and
      gelatinases by zymography. RESULTS: Resurfacing from bioengineereed skin explants
      started earlier than from normal skin but subsequently, from day 3 to day 9, the
      rate of epidermalization from bioengineered skin was only 40% (206 +/- 23 microm
      day(-1), mean +/- SEM) of that of authentic skin (521 +/- 17 microm day(-1), P <
      0.001). At culture termination at day 11, normal human skin had formed a
      multilayered and well-structured neoepidermis covering 41.0 +/- 1.2 mm2 of the
      dermal substrate while bioengineered skin produced a thinner, less organized
      epithelium covering 20.4 +/- 3.0 mm2. At this later stage, a higher expression of
      beta-defensin-2, keratin 16, Ki67 and matrix metalloproteinase (MMP)-9 was found
      in neoepidermis formed from authentic skin than from bioengineered skin.
      Activated MMP-2 was elevated in bioengineered skin-derived neoepidermis. Minor
      epithelial outgrowth was noted with either skin type on the dermal substrate
      devoid of basement membrane zone. CONCLUSIONS: Cultured normal skin explants
      produced a more uniform and expansive in vivo-like neoepidermis than
      bioengineered skin explants.

PMID- 16403093
TI  - Characteristics of Hori naevus: a prospective analysis.
AB  - BACKGROUND: Acquired, bilateral naevus of Ota-like macules or Hori naevus (HN) is
      a common dyschromia seen in Orientals. Other than the original report which
      documented the clinical spectrum in a group of 22 patients, there have not been
      many epidemiological reports of this condition. OBJECTIVES: To evaluate the
      epidemiology and clinical characteristics of HN in Asian patients. METHODS: A
      prospective analysis of 161 patients with HN seen from June 2003 to June 2004 was
      performed. RESULTS: All 161 patients in the study were women. Patients were
      Chinese (n = 155), Eurasian (n = 4), Malay (n = 1) and Indian (n = 1). The median
      age at onset was 30 years. The malar region was the most frequently affected
      area. Discrete brown macules were the most common early presentation. Confluent
      slate-grey macules occurred later. Aggravating factors included sun exposure and
      pregnancy. Sixty-seven patients reported a positive family history. CONCLUSIONS:
      We report our data on the largest series of HN in the literature so far.
      Predisposing factors in our study are Chinese race, female sex and positive
      family history. HN became progressively more confluent and grey over time,
      suggesting migration from the epidermis to the deeper dermis. More studies are
      needed to confirm the pathogenesis.

PMID- 16403094
TI  - Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors
      in 181 patients.
AB  - BACKGROUND: Polymorphic eruption of pregnancy (PEP; synonym: pruritic urticarial
      papules and plaques of pregnancy) is the most common specific dermatosis of
      pregnancy. However, its clinical characterization is controversial and its
      pathogenesis uncertain. OBJECTIVES: To evaluate clinical characteristics of and
      potential trigger factors for PEP in a large mixed ethnic population. METHODS: A
      retrospective analysis of epidemiological, clinical, immunopathological and
      obstetric findings in 181 patients with PEP seen at two university-based
      dermatological hospitals in Graz, Austria, and London, U.K. RESULTS: PEP mainly
      affected white (88%) primigravidae (70%) in late pregnancy (83%; mean +/- SD
      onset 34 +/- 5 weeks) or the immediate postpartum period (15%). The most commonly
      involved sites were the abdomen and proximal thighs (97%). Involvement of the
      whole skin, including the face, palms and soles, was only rarely observed. While
      pruritic urticarial papules and plaques were the main morphological features at
      disease onset (98%), more than one-half of the patients (51%) later developed
      polymorphous features including erythema, vesicles, and targetoid and eczematous
      lesions. Topical treatment with corticosteroids and emollients was sufficient to
      control symptoms in the majority of patients, and skin lesions resolved after a
      mean +/- SD of 4 +/- 3 weeks. Multiple gestation pregnancies were observed in 13%
      of cases, excessive maternal weight gain in 78%. CONCLUSIONS: Our data confirm
      the benign, self-limiting nature of PEP and its favourable outcome for both the
      mother and the fetus. For the first time, we have documented a characteristic
      change in morphology with disease progression. The evidence of polymorphous
      clinical features in more than one-half of the patients favours the use of the
      term PEP. Multiple gestation pregnancies and excessive maternal weight gain, but
      not fetal weight and sex, were found to be significantly associated with PEP.

PMID- 16403095
TI  - Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris:
      results of a case-control study.
AB  - BACKGROUND: It has been suggested that psychological factors such as repressing
      anger and altruistic interpersonal behaviour may play a role in the aetiology of
      chronic itching in prurigo nodularis (PN). Whether these issues are specific for
      PN or are also common in other chronic skin diseases, e.g. psoriasis, has not
      been investigated until now. OBJECTIVES: To investigate psychosomatic problem
      areas and psychiatric comorbidity in patients with PN in comparison with patients
      with psoriasis. METHODS: Ninety-four patients with PN and 91 patients with
      psoriasis were administered the Hospital Anxiety and Depression Scale, Toronto
      Alexithymia Scale, State-Trait Anger Expression Inventory, Inventory of
      Interpersonal Problems, Screening for Somatoform Disorders and the Whiteley Index
      for hypochondriasis. RESULTS: After Bonferroni post hoc adjustment, the metrical
      scales demonstrated no significant differences between patients with PN and those
      with psoriasis. There was only a tendency to less 'anger-out' and to less
      autocratic/dominant and more insecure/submissive behaviour in the patients with
      PN. Patients with PN were, in general, comparable with those with psoriasis with
      regard to alexithymia, somatization symptoms, hypochondriasis, anxiety and
      depression, with 18% cases of anxiety and 22% cases of depression. CONCLUSIONS:
      The hypotheses formulated in the literature on the specific aetiology of PN could
      not be proven for the majority of patients with PN in our study. Concerning their
      psychopathology, patients with PN were comparable with those with psoriasis.
      Therefore the clinical management of PN should include psychosomatic assessment.

PMID- 16403096
TI  - Evidence of an association between desmoglein 3 haplotypes and pemphigus
      vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris (PV, OMIM 169610) is a severe blistering disorder
      of the skin and mucous membranes, caused by the production of autoantibodies
      directed against the epithelial adhesive protein desmoglein 3. Although an
      association between PV and HLA class II alleles has been established, the genetic
      factors predisposing to the disease remain poorly understood, the rarity of PV
      hampering the recruitment of substantial patient cohorts. OBJECTIVES: To
      investigate DSG3 as a candidate PV susceptibility gene. METHODS: We examined five
      DSG3 single nucleotide polymorphisms (rs8085532, rs3911655, rs3848485, rs3794925
      and rs1466379) in two case-control datasets respectively originating from the
      U.K. (62 PV patients, 154 controls) and northern India (28 patients, 98
      controls). RESULTS: In the U.K. sample, we observed a significant association
      between PV and the DSG3*TCCTC haplotype (Fisher's exact test P = 0.002). A
      related haplotype (DSG3*TCCCC) was associated with PV in the Indian dataset (P =
      0.002). We also found that all British and Indian patients bearing DSG3 risk
      haplotypes carried at least one copy of a PV-associated HLA allele. CONCLUSIONS:
      These results suggest that genetic variation of DSG3 may be an additive risk
      factor predisposing to PV and warrant further investigations of this gene.

PMID- 16403097
TI  - Imiquimod-induced regression of actinic keratosis is associated with infiltration
      by T lymphocytes and dendritic cells: a randomized controlled trial.
AB  - BACKGROUND: Imiquimod 5% cream is a topically applied immune response modifier
      that has been shown to give effective treatment of actinic keratosis (AK). The
      therapeutic effects of imiquimod are likely to involve the provocation of a
      cutaneous immune response against abnormal cells, an assumption based on a strong
      correlation between complete clearance rates and the severity of the local skin
      reactions (erythema, oedema, erosion/ulceration, weeping/exudation and
      scabbing/crusting); however, no clinical studies have conclusively proved this
      mechanism. OBJECTIVES: To determine the nature of cellular infiltrates induced by
      the application of imiquimod to AK lesions and to study cells involved in the
      cutaneous immune response. METHODS: Eighteen patients participated in this phase
      I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled
      patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle
      cream and applied study cream to five lesions on the scalp, forearm or upper
      trunk once daily, three days per week for up to 16 weeks. Each patient had punch
      biopsies of two distinct AK lesions: a lesion was biopsied before treatment to
      obtain baseline biomarker levels, and a different lesion was biopsied after 2
      weeks of treatment. Biopsy specimens were examined using routine and
      immunohistochemical staining. RESULTS: The imiquimod group showed statistically
      significant increases from baseline to week 2 in tissue biomarker levels for CD3,
      CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences
      were seen for the vehicle group. Complete clearance of all treated AK lesions was
      achieved in five of 11 (45%) imiquimod patients and in none of six vehicle
      patients. CONCLUSIONS: Imiquimod stimulates a cutaneous immune response
      characterized by increases in activated dendritic cells and CD4+ and CD8+ T
      cells.

PMID- 16403098
TI  - Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.
AB  - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease mostly
      associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and
      BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL
      13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been
      detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms
      may affect cytokine production and contribute to susceptibility to autoimmune
      diseases. Until now, no cytokine gene polymorphism study has been conducted on
      patients with BP. OBJECTIVES: We aimed to determine whether the genetic
      polymorphisms of the cytokine genes might influence the development of BP.
      METHODS: DNA samples were obtained from 96 BP patients and 174 control subjects.
      Using direct sequencing and microsatellite genotyping, we examined 23
      polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1
      receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and
      IFN-gamma genes. RESULTS: Although the BP patients were more likely to carry the 
      511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance
      disappeared after correction for multiple testing (Pc). There was complete
      linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene.
      In female patients with BP, the associations with IL-1beta (-511T) and (-31C)
      alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No
      significantly different allelic and genotypic distributions of other cytokine
      gene polymorphisms could be found between the patients with BP and controls.
      Moreover, no association with the extent of disease involvement (localized or
      generalized) was observed. CONCLUSIONS: The IL-1beta (-511) and (-31)
      polymorphisms were significantly associated with BP in women. The other genetic
      polymorphisms of cytokine genes that we analysed do not appear to be associated
      with BP susceptibility in our Chinese population.

PMID- 16403099
TI  - Female pattern hair loss, sebum excretion and the end-organ response to
      androgens.
AB  - BACKGROUND: Although female pattern hair loss can be a feature of
      hyperandrogenism, many women with hair loss show no clinical or biochemical
      features of androgen excess. It is possible that hair loss in nonhyperandrogenic
      women is due to a high level of response to androgens by scalp hair follicles. In
      this study we explored this idea using sebum excretion as a marker of the
      cutaneous end-organ response to androgens. OBJECTIVES: To test the hypothesis
      that hair loss in nonhyperandrogenic women is due to an increased cutaneous end
      organ response to androgens. METHODS: We studied 100 women, 41 with female
      pattern hair loss (without hirsutism), 29 with hirsutism (with and without scalp
      hair loss) and 30 subjects without hair problems. We measured hair density on the
      frontal scalp, forehead sebum excretion, serum free androgen index (FAI), and
      body mass index (BMI). RESULTS: The mean FAI was significantly raised in hirsute
      women compared with nonhirsute women (P < 0.001), but there was no difference in
      FAI levels between nonhirsute women with and without hair loss. The mean BMI was
      also significantly elevated in hirsute women (P < 0.01) but there was no
      difference in BMI between nonhirsute women with and without hair loss. The mean
      sebum excretion was higher in hirsute women than nonhirsute women but the
      difference was not statistically significant. There was no difference in sebum
      excretion between nonhirsute women with and without hair loss. There was no
      correlation between hair density and sebum excretion. CONCLUSIONS: Our results
      show that sebum excretion is not elevated in women with female pattern hair loss.
      This may indicate that different androgen-response pathways operate in
      controlling hair growth and sebum excretion. The alternative explanation is that
      nonandrogenic mechanisms are involved in mediating hair loss in some women.

PMID- 16403101
TI  - Current eczema in children is related to Der f 1 exposure but not to Der p 1
      exposure.
AB  - BACKGROUND: Mite allergen exposure is an important risk factor for specific IgE
      production and is associated with asthma, hay fever and eczema. Whether these
      associations are independent of mite species has not been investigated so far.
      OBJECTIVES: To investigate the influence of exposure to the major house dust mite
      (HDM) allergens Der p 1 and Der f 1 on sensitization, respiratory symptoms, and
      especially on eczema and related skin symptoms in 6-7-year-old children. METHODS:
      In a cross-sectional study in Augsburg (Bavaria, Germany) 1669 school beginners
      (mean age 6.5 years) were investigated in 1996. The concentrations of Der p 1 and
      Der f 1 were measured in dust samples from mattresses of 1081 children by enzyme
      linked immunosorbent assay. The prevalence of atopy-related health outcomes was
      assessed by questionnaire, dermatological examination, skin prick testing and
      determination of specific serum IgE concentrations by radioallergosorbent test.
      Information about covariates was taken from questionnaires and interview data.
      Logistic regression was used to adjust for confounding. RESULTS: The mean
      concentrations of Der p 1 and Der f 1 were 0.68 and 0.79 microg g(-1) dust,
      respectively. The relationship between the two species-specific allergens in
      individual homes was poor (Pearson correlation 0.2). Influencing variables were
      bedroom-sharing (Der p 1) and social status of the parents (Der f 1). Respiratory
      diseases were positively associated with both allergen concentrations [odds ratio
      (OR) between 1.1 and 2.6]. These associations were significant for sneezing
      attacks (Der p 1 and Der f 1). Reported prevalence of current (in the last 12
      months) itchy skin rash was significantly associated with exposure to Der f 1
      only (OR 2.4, P < 0.003); also a diagnosis of atopic eczema on the day of
      investigation was positively associated with Der f 1 only (OR 1.8, P = 0.14).
      CONCLUSIONS: Studies on the effects of HDM exposure on eczema and allergies
      should consider specific effects of different mite species. This might have
      implications on assessment of allergen exposure and consecutive prevention or
      therapeutic measures.

PMID- 16403100
TI  - Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are
      major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA
      class II alleles and disease severity.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial
      blistering disease, is associated with circulating IgG and/or IgA autoantibodies
      against several basement membrane zone antigens. The heterogeneity of clinical
      presentation and diversity of target autoantigens have contributed to
      difficulties in characterizing this condition immunologically. OBJECTIVES: To
      analyse serum autoantibody profile and HLA class II alleles in MMP patients and
      to correlate this with the clinical presentation of disease. METHODS: Well
      defined subgroups consisting of 124 patients with MMP were examined for IgG and
      IgA reactivity with immunoblotting using human epidermal, dermal and placental
      amnion proteins. The results were further analysed on the basis of detailed
      clinical (sites of involvement and disease severity) and immunopathological
      criteria (immunofluorescence study and HLA class II alleles). RESULTS: Immunoblot
      assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or
      IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains,
      120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly
      by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%),
      and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+
      sera also reacted with at least one of the BP180 antigens. Over 85% of patients
      with reactivity to beta4 integrin had ocular involvement. In most cases of MMP,
      more severe clinical features were associated with antibody reactivity to
      multiple basement membrane zone antigens, as well as reactivity to multiple BP180
      component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated
      with a more severe phenotype. In addition, the subset-dependent autoantibody
      reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04
      and DRB1*11. CONCLUSIONS: Our results confirmed that BP180 is a major autoantigen
      targeted by the sera of patients with MMP. The disease-prevalent HLA class II
      alleles and humoral autoimmune response against the particular subsets of
      antigenic epitope(s) within BP180 ectodomain may contribute to the
      clinicopathological significance and disease severity of MMP.

PMID- 16403102
TI  - Prenatal diagnosis for severe inherited skin disorders: 25 years' experience.
AB  - BACKGROUND: Over the last 25 years there have been major advances in methods for
      prenatal testing of inherited skin disorders. Since 1979, our group at the St
      John's Institute of Dermatology has performed 269 prenatal diagnoses, using a
      variety of approaches, including fetal skin biopsy (FSB), chorionic villus
      sampling (CVS) and preimplantation genetic diagnosis (PGD). OBJECTIVES: This
      study was designed to review the clinical indications, testing procedures and
      laboratory analyses for all prenatal tests conducted at St John's over this
      period. METHODS: FSBs were examined for morphological and, when relevant or
      feasible, immunohistochemical abnormalities. The DNA-based tests involved
      screening by nucleotide sequencing, restriction enzyme digests or, in a few
      cases, by linkage analysis. Results Of the 269 tests, 191 were FSB, 76 were CVS
      and two were PGD. The major indications for FSB were epidermolysis bullosa (EB)
      (138 cases, including 88 junctional and 48 dystrophic), ichthyoses (37 cases,
      including 22 tests for harlequin ichthyosis) and oculocutaneous albinism (12
      cases). Of the CVS procedures, 75 were for EB (40 junctional, 35 dystrophic) and
      one was for the EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome. Both
      of the PGD procedures were for the skin fragility-ectodermal dysplasia syndrome.
      All tests provided accurate diagnoses and the fetal loss rate was approximately
      1% for both FSB and CVS. CONCLUSIONS: The development of prenatal testing has
      proved to be of great benefit for individuals or couples at risk of having
      children with severe inherited skin disorders and, in the absence of a cure,
      prenatal testing along with appropriate counselling has become an important
      translational benefit of basic research and an integral part of clinical
      management.

PMID- 16403103
TI  - Allergic contact dermatitis in children: should pattern of dermatitis determine
      referral? A retrospective study of 500 children tested between 1995 and 2004 in
      one U.K. centre.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) increases with age, and a
      prevalence of between 13.3% and 24.5% has been reported. Patch testing infants
      may be particularly difficult, and false-positive reactions may occur.
      OBJECTIVES: The purpose of this retrospective study was to determine whether the
      site of primary dermatitis in children could predict a diagnosis of ACD. The
      current frequency of sensitization in children was also evaluated and the main
      sensitizing substances among children were verified. METHODS: Between 1995 and
      2004, 500 children were patch tested and entered on to the patch test database at
      Leeds General Infirmary. Analysis of the database included identifying the
      presenting patterns of eczema and reviewing the patch test results for each
      child. RESULTS: Of the children, 133 (27%) had one or more positive patch test
      result. The effect of age on the likelihood of a positive patch test was highly
      significant (P < 0.001). Girls were significantly more likely to have a positive
      patch test compared with boys: odds ratio for a positive test 0.62 (95%
      confidence interval 0.41-0.95; P = 0.029). Type IV allergy to nickel (33%) was
      the most frequent finding. Reactions to fragrance mix (18%), cobalt (11%),
      mercapto chemicals, Myroxylon pereirae and p-phenylenediamine (each 8%) were the
      next most common. No statistical significance was found in the relationship
      between the site of primary dermatosis and a positive patch test result.
      CONCLUSIONS: The pattern of presenting dermatitis in children should not
      determine referral for patch testing. Any child with persistent eczema should be
      referred for patch testing.

PMID- 16403104
TI  - Emergence of two populations of methicillin-resistant Staphylococcus aureus with
      distinct epidemiological, clinical and biological features, isolated from
      patients with community-acquired skin infections.
AB  - BACKGROUND: Community-acquired skin and soft-tissue infections due to methicillin
      resistant Staphylococcus aureus (MRSA) are an emerging clinical and
      epidemiological problem. OBJECTIVES: To characterize community-acquired skin
      infections caused by S. aureus, and especially MRSA. METHODS: From November 1999
      to December 2003, we conducted in a French hospital a prospective
      epidemiological, clinical and bacteriological study of skin infections acquired
      in the community, applying strict criteria for true community-acquired MRSA (CA
      MRSA) and health-care-associated MRSA (HCA-MRSA). RESULTS: One hundred and ninety
      seven patients had 207 skin infections (154 primary and 53 secondary infections).
      Twenty-two (11%) patients had skin infections caused by MRSA. The incidence of
      MRSA skin infections acquired in the community rose from 4% in 2000 to 17% in
      2003, but the increase was not statistically significant. Six patients (3%) were
      infected by CA-MRSA and 15 (8%) by HCA-MRSA; one patient was lost to follow-up
      and could not be classified. CA-MRSA and HCA-MRSA had different epidemiological,
      clinical and biological characteristics. CA-MRSA infections were more severe than
      HCA-MRSA infections: all the CA-MRSA infections (six of six, 100%) required
      surgical treatment, compared with only two (15%) of 13 with HCA-MRSA infection (P
      < 0.001). CA-MRSA all belonged to the same clonal strain, harbouring an agr type
      3 allele and the Panton-Valentine leucocidin genes (not detected in HCA-MRSA) and
      possessing a specific antibiotype. CONCLUSIONS: Two populations of MRSA causing
      skin infections are emerging in the French community, with distinct
      epidemiological, clinical and biological characteristics.

PMID- 16403105
TI  - Facial skin fluorescence as a marker of the skin's response to chronic
      environmental insults and its dependence on age.
AB  - BACKGROUND: Throughout life facial skin is exposed to a variety of adverse
      environmental conditions and is constantly required to repair itself. The rate of
      epidermal cell proliferation is indicative of the skin's repair rate and can be
      monitored noninvasively in vivo using skin intrinsic fluorescence markers.
      OBJECTIVES: The goal of the present study was to assess the effects of ageing,
      geographical region, ethnic origin and season on the ability of facial skin to
      repair itself in the presence of chronic environmental insults using in vivo
      fluorescence spectroscopy. METHODS: Skin fluorescence emission was measured on
      the cheeks of 522 individuals in winter and repeated in summer in five different
      geographical locations in the Asia-Pacific region. Fluorescence emission was also
      measured from 80 caucasians of fair complexion in the United States (New Jersey
      area) on the face and on a relatively protected area (upper inner arm). The age
      range of the participants was 14-75 years. RESULTS: We found that epidermal
      proliferation rates decrease monotonically with age, while the fluorescence of
      collagen and elastin cross-links increases with age indicating accumulation of
      advanced glycation end-products. These trends were independent of geographical
      region, ethnic origin and season of measurement. Epidermal proliferation rates of
      facial skin were higher than those of unexposed sites; they may be 10 times
      higher in younger (second decade) than in older (seventh decade) individuals, and
      they decrease with age at rates 10 times faster compared with those of unexposed
      sites. CONCLUSIONS: This is the first time that epidermal proliferation and its
      dependence on ageing have been measured noninvasively on the human face. The
      higher tryptophan fluorescence values on the face vs. the protected site are
      indicative of accelerated rates of epidermal proliferation in the presence of
      chronic environmental insults. The repair potential of facial skin, i.e. its
      ability to maintain high proliferation rates, is maximal in younger populations
      and gradually decreases with age.

PMID- 16403106
TI  - Ultraviolet radiation exposure pattern in winter compared with summer based on
      time-stamped personal dosimeter readings.
AB  - BACKGROUND: Personal annual ultraviolet (UV) radiation data based on daily
      records are needed to develop protective strategies. OBJECTIVES: To compare UV
      radiation exposure patterns in the winter half-year (October-March) and the
      summer half-year (April-September) for Danish indoor workers. METHODS: Nineteen
      indoor workers (age range 17-56 years) wore personal UV dosimeters, measuring
      time-stamped UV doses continuously during a year. The corresponding sun exposure
      behaviour was recorded in diaries. Similar data were collected for 28 volunteers
      during sun holidays in the winter half-year. The relationship between UV dose and
      sun exposure behaviour was analysed. RESULTS: The ambient UV dose during the
      winter in Denmark (at 56 degrees N) was 394 standard erythema doses (SED) or
      10.5% of the annual ambient UV dose. In winter compared with summer the subjects
      had: (i) a lower percentage of ambient UV radiation, 0.82% vs. 3.4%; (ii) a lower
      solar UV dose in Denmark, 3.1 SED (range 0.2-52) vs. 133 SED (range 69-363);
      (iii) less time outdoors per day with positive dosimeter measurements, 10 min vs.
      2 h; and (iv) no exposure (0 SED) per day on 77% vs. 19% of the days. Sun
      holidays outside Denmark in winter gave a median 4.3 SED per day (range 0.6-7.6)
      and 26 SED (range 3-71) per trip. CONCLUSIONS: In the winter half-year indoor
      workers received a negligible UV dose from solar exposure in Denmark and needed
      no UV precautions. No UV precautions are needed from November to February during
      holidays to latitudes above 45 degrees N, while precautions are needed the whole
      year around at lower latitudes.

PMID- 16403107
TI  - Ciclosporin vs. clobetasol in the topical management of atrophic and erosive oral
      lichen planus: a double-blind, randomized controlled trial.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease that can
      be painful, especially in the atrophic and erosive forms. Several drugs have been
      used with varying results, but most treatments are empirical, and do not have
      adequate control groups or correct study designs. OBJECTIVES: To compare the
      effectiveness of clobetasol and ciclosporin in the topical management of OLP and
      to evaluate which is more cost-effective and which gives the longest remission
      from signs and symptoms. METHODS: A randomized, comparative, double-blind study
      was designed. Forty consecutive patients were divided into two groups to receive
      clobetasol propionate or ciclosporin for 2 months. Both drugs were placed in 4%
      hydroxyethyl cellulose bioadhesive gel. Antimycotic prophylaxis was also given.
      After the end of therapy, patients underwent a 2-month follow-up. RESULTS:
      Eighteen of 19 clobetasol-treated patients (95%) improved after 2 months of
      therapy, while 13 of 20 ciclosporin-treated patients (65%) had a clinical
      response (P = 0.04). Symptomatology improved in 18 clobetasol-treated patients
      (95%) and in 17 ciclosporin-treated patients (85%) (not statistically
      significantly different). Two months after the end of therapy, 33% of clobetasol
      treated patients and 77% of ciclosporin-treated patients were stable (P = 0.04).
      Clobetasol produced significantly more side-effects than ciclosporin (P = 0.04).
      The daily cost of ciclosporin treatment was 1.82 compared with 0.35 for
      clobetasol therapy. CONCLUSIONS: Clobetasol is more effective than ciclosporin in
      inducing clinical improvement, but the two drugs have comparable effects on
      symptoms. Conversely, clobetasol gives less stable results than ciclosporin when
      therapy ends and has shown a higher incidence of side-effects. The daily cost of
      ciclosporin is more than five times higher than clobetasol.

PMID- 16403108
TI  - Randomized, double-blind, placebo-controlled prospective study of the efficacy of
      topical anaesthesia with a eutetic mixture of lignocaine 2.5% and prilocaine 2.5%
      for topical 5-aminolaevulinic acid-photodynamic therapy for extensive scalp
      actinic keratoses.
AB  - BACKGROUND: Photodynamic therapy (PDT) is an effective treatment modality for the
      treatment of extensive scalp actinic keratoses (AKs), but pain is a significant
      drawback when treating large areas with topical PDT using 5-aminolaevulinic acid
      (ALA) as sensitizer. A recent study has shown that use of tetracaine gel (Ametop)
      did not significantly reduce pain associated with PDT. OBJECTIVES: To assess the
      benefit of a eutetic mixture of lignocaine 2.5% and prilocaine 2.5% (Emla) on
      pain during topical ALA-PDT treatment of scalp AKs. METHODS: Fourteen men aged 59
      83 years with extensive scalp AKs were recruited into a double-blind placebo
      controlled study. Two treatment fields were defined (right and left frontal
      scalp) and were treated 2 weeks apart. These fields were randomized to receive
      either Emla or Aqueous cream as first or second treatment. ALA 20% cream was
      applied for 4 h. Topical anaesthesia or Aqueous cream was applied for 2 h. Pain
      was assessed using a visual analogue scale (0-100 mm) at 3, 6, 12 and 16 min. The
      instrument used for this was a blinded counter with one side reading 'no pain' to
      'worst pain ever' with a numerical scale (0-100) on the reverse side. Pain scores
      were assessed looking at median and interquartile range and confidence intervals
      and calculating differences between treatment groups and analysing them using a
      paired t-test. RESULTS: Thirteen patients received treatment to both fields. No
      significant difference in mean pain scores was seen with the use of Emla cream
      compared with placebo during treatment of scalp AKs (P = 0.328). There was no
      significant difference in requirement for oral analgesia following PDT between
      the two groups (P = 0.06). CONCLUSIONS: Our data do not support the routine use
      of topical anaesthesia with Emla for topical PDT.

PMID- 16403109
TI  - An assessment of the quality of life in older patients with skin disease.
AB  - BACKGROUND: There are few data regarding quality of life in older people with
      skin disease, particularly concerning those with skin cancer. Access to U.K.
      secondary care dermatological services is increasingly focusing on skin cancer,
      which may have a negative effect on waiting times for patients with rashes.
      OBJECTIVES: To assess the quality of life in patients aged 65 years and over and
      to determine how this relates to type and extent of skin disease. METHODS: One
      hundred consecutive new dermatology patient referrals aged 65 years and above had
      quality of life assessed by the Dermatology Life Quality Index (DLQI), the
      Hospital Anxiety and Depression Scale (HADS) and the Illness Perception
      Questionnaire. Patients were examined for type and extent of skin disease.
      RESULTS: There were 49 men (mean age 75.1 years) and 51 women (mean age 75.0
      years). Fifty-five per cent of patients had been referred with one or more
      lesions (76% premalignant or malignant) and 45% had rashes. There was no
      significant difference between the quality of life scores of men vs. women
      regarding all three of the questionnaires. However, patients with rashes scored
      significantly higher (i.e. poorer quality of life) on all but one of the
      questionnaire parts compared with patients with lesions. Patients with more
      extensive disease had significantly higher DLQI scores. CONCLUSIONS: Older people
      suffering from rashes had significantly poorer quality of life than patients with
      lesions, even those with skin cancer. The quality of life is negatively
      associated with extent of skin disease. Access to specialist dermatological care
      should take into account the suffering caused by extensive skin diseases. DLQI
      and a general quality of life questionnaire such as the HADS are quick to deliver
      and to score, particularly in the setting of a busy outpatient department. They
      provide an excellent screening tool for psychological problems in older people
      with skin disease.

PMID- 16403110
TI  - Physical friction is under-recognized as an irritant that can cause or contribute
      to contact dermatitis.
AB  - BACKGROUND: The role of physical friction as an irritant in the causation of
      contact dermatitis is under-recognized. Frictional dermatitis is defined as an
      eczematous process in which physical frictional trauma contributes to the
      induction of a dermatitis process. OBJECTIVES: To examine the clinical background
      of patients in whom friction was contributing to dermatitis. METHODS: Over a 30
      month period during which 2700 new patients were seen, frictional irritancy was
      identified as playing a role in the dermatosis in 31 cases: in 27 of these, case
      notes were evaluated for a range of parameters. RESULTS: Physical friction was
      identified as causing or contributing to the dermatitis in 18 men and nine women,
      mean age at onset 42 years. The hands, usually the fingers of the dominant hand,
      were affected in all but two cases. Occupational frictional activities were found
      in 25 cases: commonly handling small metal components, paper, cardboard or
      fabric, and driving. Potential frictional activities in hobbies were noted in 12
      cases. Wet work irritancy contributed in four cases (15%). Patch testing showed
      relevant contact allergies as cofactors in seven of 25 subjects tested (26%).
      Psoriasis was a cofactor in four (15%), and atopic dermatitis in 11. The study
      was selective, being based in a teaching hospital clinic with a special interest
      in contact dermatitis. Frictional irritancy is often one of several factors
      contributing to dermatitis. CONCLUSIONS: The contribution of friction to contact
      dermatitis is under-recognized probably because dermatologists do not think about
      the potential for physical forces to induce eczematous changes in the skin.

PMID- 16403111
TI  - Chronic obesity lymphoedematous mucinosis: three cases of pretibial mucinosis in
      obese patients with pitting oedema.
AB  - Pretibial mucin deposition on the shins is known as pretibial myxoedema. We
      report three patients with pretibial mucinosis without thyroid disease. The
      patients were characterized clinically by morbid obesity and bilateral lower
      extremity pitting oedema with gradual and painless onset, and that did not
      involve the feet and ankles. Vesicles, semitranslucent papules or a woody plaque
      were found on the shins. Histologically, patients showed characteristic features
      of epidermal atrophy with effacement of the rete ridge pattern, separation of
      collagen bundles associated with oedema with stellate to linear fibroblasts,
      upward-running increased capillary and small vessels with haemosiderin
      deposition, and mucin deposition at the superficial papillary dermis and around
      the vessels. We propose that the present cases of 'chronic obesity
      lymphoedematous mucinosis' belong to the clinical entity of pretibial mucinosis.

PMID- 16403113
TI  - Towards characterization of palmoplantar keratoderma caused by gain-of-function
      mutation in loricrin: analysis of a family and review of the literature.
AB  - Loricrin keratoderma is an autosomal dominant palmoplantar keratoderma
      heterogeneous in clinical appearance. We report a family with diffuse ichthyosis
      and honeycomb palmoplantar keratoderma but no occurrence of pseudoainhums or
      autoamputations. All patients were born as collodion babies and displayed
      prominent knuckle pads. We identified the previously reported mutation 730insG in
      LOR, which elongates loricrin by 22 amino acids because of delayed termination.
      As pseudoainhums are missing in all patients of the family reported, we propose
      two compulsory features of loricrin keratoderma: (i) honeycomb palmoplantar
      keratoderma and (ii) diffuse ichthyosiform dermatosis. Therefore we suggest that
      the condition should be described clinically as 'honeycomb palmoplantar
      keratoderma with ichthyosis'. Furthermore, we have assessed the amounts of
      transcript of LOR using pyrosequencing. This revealed an equal expression of
      mutant and wild-type alleles of LOR in an affected individual. These findings
      further underline the gain-of-function theory for mutant LOR in loricrin
      keratoderma.

PMID- 16403112
TI  - Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component
      and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture
      microdissection.
AB  - The presence of a dominant B- or T-cell clone is an important diagnostic
      criterion for distinguishing cutaneous lymphomas from lymphoid reactive
      infiltrates. Rarely, a combined B- and T-cell rearrangement can be detected from
      a single sample. In such instances, genotypic analysis does not permit
      differentiation of the coexistence of a T- and B-cell lymphoma from a single
      clone harbouring a monoclonal rearrangement for both immunoglobulin heavy chain
      and T-cell receptor genes. We herein report a case of a skin tumour consistent
      with a dense cutaneous lymphoid infiltrate showing a double prominent B- and T
      cell component. A dual B- and T-cell clonality was detected by polymerase chain
      reaction from whole-tissue DNA sample. Genotypic analysis with DNA, obtained
      after laser-assisted microdissection from the B-cell population, again showed
      both T- and B-cell monoclonal rearrangements. Conversely, the microdissected T
      cell population did not reveal a clonal pattern. The diagnosis of cutaneous B
      cell lymphoma with a dual B- and T-cell genotype was established. This
      description illustrates the diagnostic usefulness of laser-capture
      microdissection in cutaneous lymphomas presenting dual genotype.

PMID- 16403114
TI  - Skin manifestations in a case of trisomy 16 mosaicism.
AB  - We present a 48-year-old man with unilateral dermatological manifestations
      including hypertrichosis, telangiectasia, hyperkeratosis and hyperpigmentation.
      Additional findings included skeletal abnormalities and left-sided hearing loss.
      Skin biopsies showed changes characteristic of porokeratosis. Fibroblast
      karyotyping from affected skin demonstrated trisomy 16 mosaicism, in contrast to
      the normal karyotype in unaffected skin and blood lymphocytes. The possible role
      of trisomy 16 in porokeratosis is discussed.

PMID- 16403115
TI  - Nodal follicular dendritic cell sarcoma of the axilla presenting as cellulitis.

PMID- 16403116
TI  - Cutaneous chondroma with overlying pigmentation clinically mimicking
      dermatofibroma.

PMID- 16403117
TI  - Etanercept for the treatment of severe childhood psoriasis.

PMID- 16403118
TI  - Cutaneous malignant fibrous histiocytoma of the scalp in a renal transplant
      recipient.

PMID- 16403119
TI  - Skin grafting as a therapeutic approach in pretibially restricted junctional
      epidermolysis bullosa.

PMID- 16403120
TI  - The role of digital photography and electronic referral in the triage of patients
      with suspected skin cancer.

PMID- 16403121
TI  - Alopecia universalis treated with bone morphogenetic protein?

PMID- 16403122
TI  - Doxycycline for the treatment of paronychia induced by the epidermal growth
      factor receptor inhibitor cetuximab.

PMID- 16403123
TI  - Subepidermal bullous dermatosis with IgA antibodies against 200- and 280-kDa
      epidermal antigens after initiation of ultraviolet B therapy for psoriasis.

PMID- 16403124
TI  - Adult T-cell leukaemia/lymphoma masquerading as a hair dye allergy.

PMID- 16403125
TI  - Importance of repeat testing in the diagnosis of penicillin allergy.

PMID- 16403126
TI  - Nicorandil-associated perianal ulceration: a case series of 10 patients.

PMID- 16403127
TI  - Granulocytic sarcoma (leukaemia cutis) in association with basal cell carcinoma.

PMID- 16403129
TI  - Providing integrated mental health services: a policy and management perspective.
AB  - OBJECTIVE: To review the challenge of providing integrated mental health services
      from a policy and health management perspective. CONCLUSIONS: The provision of
      integrated mental health services involving specialist mental health services,
      general practitioners, psychiatric disability and rehabilitation services and
      public community health services is a major challenge in the Australian health
      care context and is increasingly an expectation of the community. Government,
      Divisions of General Practice and public community health policy and many
      Government, State and local initiatives have attempted to address this challenge.
      However, much remains to be done, including culture change within services and
      professions and the development of technology to support integrated service
      provision.

PMID- 16403128
TI  - Power and knowledge in psychiatry and the troubling case of Dr Osheroff.
AB  - OBJECTIVE: To consider the state of knowledge in psychiatry with reference to the
      'Osheroff debate' about the treatment of depression. METHOD: A review of the key
      philosophical issues regarding the nature of knowledge applied to the Osheroff
      case. RESULTS: There is an apparent dichotomy between knowledge derived from a
      reductionist scientific method, as manifest in evidence-based medicine, and that
      of a narrative form of knowledge derived from clinical experience. The Focauldian
      notion of knowledge/power and knowledge as discourse suggests that scientific
      knowledge dominates over narrative knowledge in psychiatry. The implication of
      this applied to the Osheroff case is the potential annihilation of all forms of
      knowledge other than science. CONCLUSIONS: Knowledge in psychiatry is a
      pluralist, rather than singularly scientific enterprise. In the Osheroff case,
      the potential for scientific knowledge to abolish other forms of knowledge posed
      a serious threat of weakening the profession. In the light of the current debate
      about best practice, there is a need for reconsideration of the implications of
      Osheroff.

PMID- 16403131
TI  - The role of the consumer in the leadership and management of mental health
      services.
AB  - OBJECTIVE: To reflect on consumer involvement in the leadership and management of
      mental health services through consideration of relevant policy directives,
      pertinent literature and current practice, and to consider the role of
      psychiatrists in promoting consumer involvement. CONCLUSIONS: Both Australia and
      New Zealand have significant policy directives in relation to consumer
      involvement in mental health services. The actual realization of consumer
      involvement within the mental health sector is extremely variable and the extent
      of genuine participation highly questionable, particularly in regard to
      leadership and management roles. It is important that the rationale for consumer
      involvement is continually highlighted and understood by all mental health
      professionals, including psychiatrists, so as to discourage the practice of
      including consumers solely for the sake of adhering to political policies. The
      attitudes of health professionals have been identified as having the most
      significant impact on consumer involvement. It is questionable whether the
      critical contribution of consumer involvement in mental health services should
      remain dependent on the attitudes of non-consumers within the sector. In New
      Zealand, a paradigm shift is occurring with consumer involvement moving from a
      construct of 'participation' to one of 'leadership'. Psychiatrists can, and
      should, play a significant role in advocating for the development of mental
      health services in directions which support and promote consumer involvement at
      all levels.

PMID- 16403130
TI  - Enabling clinicians to become the quality leaders in a mental health service.
AB  - OBJECTIVE: To show how clinicians can become the leaders of 'quality' in a mental
      health services, using the example of developments within Northern Sydney Health
      (NSH) Area Mental Health Services (AMHS). METHOD: In the absence of an existing
      integrated area quality programme, NSH AMHS implemented a quality improvement
      programme whereby staff at the coalface would become the leaders in 'quality'
      guided and supported by the newly established Quality Unit. This innovative
      approach is consistent with evidence that suggests that clinicians need to 'own'
      quality improvement initiatives and embed them into everyday practice, rather
      than see them as the role of a designated 'quality' person/s. RESULTS: Within 12
      months the service trained over 100 clinicians in Clinical Practice Improvement
      (CPI) methodology and currently has over 20 CPI projects with an identified
      measurable outcome. As well, it has provided over 200 staff with in-services on
      quality improvement approaches and trained 45 staff in root cause analysis.
      Training of eight clinicians in the use of the Minitab statistical package has
      allowed data analysis and charting to identify opportunities for improvement.
      CONCLUSION: The handing of 'quality' back to clinicians of the AMHS has provided
      a framework for improved outcomes for patients and carers. This approach to
      service improvement is transferable to other mental health services.

PMID- 16403132
TI  - Identifying and communicating clinical risk.
AB  - OBJECTIVE: To develop a simple and easy-to-complete tool to communicate
      identified clinical risks. CONCLUSIONS: Literature and Internet searching did not
      yield a simple and easy-to-use method of identifying and communicating risks. A
      Risk Identification Form was developed and may be of interest to mental health
      services wishing to implement a similar tool to document and communicate clinical
      risk identified during assessment of mental health consumers.

PMID- 16403133
TI  - Issues in the pharmacological treatment of anxiety disorders.
AB  - OBJECTIVE: To review the most salient issues in the pharmacotherapy of anxiety
      disorders. These pertain to means of achieving greater efficacy, accelerating the
      onset of therapeutic action, improving side-effect profile and tolerability,
      decreasing the propensity to induce therapeutic dependence and achieving better
      long-term outcome. CONCLUSIONS: By and large, pharmacological agents with greater
      efficacy in anxiety disorders have yet to be developed. Several strategies have
      been used with some success to make medications for anxiety disorders work faster
      and to lessen their side-effect burden. The field of psychopharmacology has yet
      to find ways of lessening or eliminating the problem of therapeutic drug
      dependence and, even more so, of minimizing the risk of relapse following the
      cessation of medication.

PMID- 16403134
TI  - Psychiatric comorbidity: concepts, controversies and alternatives.
AB  - OBJECTIVE: To review various concepts of psychiatric comorbidity, their
      implications, surrounding controversies and underlying issues. A further aim is
      to propose an alternative term that might be more clinically useful and
      meaningful for describing the coexistence of mental disorders. CONCLUSIONS: There
      is wide dissatisfaction with the concepts of psychiatric comorbidity because of
      different meanings, speculations on which they are often based and consequent
      confusion. Although the coexistence of mental disorders should be studied further
      so that any patterns in the corresponding relationships can be elucidated, there
      is a need for conceptual clarity and making the concept more meaningful for
      clinical practice and treatment. With that in mind, this present paper proposes
      avoidance of the term comorbidity and introduction of the term 'co-occurrence'.
      The latter is defined in this article, and the distinction made between
      diagnostic co-occurrence and clinically significant co-occurrence.

PMID- 16403135
TI  - Patterns of current comorbidity in young help-seekers: implications for service
      planning and delivery.
AB  - OBJECTIVE: To identify the pattern of current comorbidity in young help-seekers
      referred to a specialist mental health service. METHOD: One hundred and forty
      nine participants were assessed for current psychiatric diagnoses following their
      referral to ORYGEN Youth Health. RESULTS: Seventy-eight per cent of the sample
      rated for at least one diagnosis with almost half the sample presenting with two
      or more disorders. Next to comorbid depression and anxiety, comorbidity between
      substance use disorders and mood and anxiety disorders was the most prominent
      pattern of comorbidity in the sample. CONCLUSIONS: The present findings suggest
      that integration between mental health and substance abuse services is well
      overdue and must be addressed at policy, service system and clinical levels.

PMID- 16403136
TI  - Preventing EPISODE II: relapse prevention in first-episode psychosis.
AB  - OBJECTIVE: This paper outlines a rationale for expanding research and clinical
      innovations focused upon relapse prevention following a first episode of
      psychosis. Some general principles for further progress are extracted from an
      overview of the first-episode psychosis (FEP) relapse literature. A cognitive
      behaviour therapy intervention for relapse prevention for FEP, that has been
      developed at the Early Psychosis Prevention and Intervention Centre, is described
      to illustrate these principles. CONCLUSIONS: Further progress is needed in
      refining interventions specific to the prevention of relapse following FEP.
      Future progress is dependent upon improved understanding of the interaction of
      biological, interpersonal and psychological processes underpinning relapse.

PMID- 16403137
TI  - Diagnostic stability in patients with first-episode psychosis.
AB  - OBJECTIVE: To examine the short-term stability of Diagnostic and Statistical
      Manual of Mental Disorders (4th edn; DSM-IV) and International Classification of
      Diseases (10th revision; ICD-10) diagnoses in a group of patients with first
      episode psychosis. METHOD: Sixty patients with first-episode psychosis admitted
      consecutively to Roozbeh Hospital, Tehran, were sampled; their illnesses could
      not be attributed to any medical or substance-induced conditions. Patients were
      assessed at the time of discharge from the hospital, and at 3, 6 and 12 month
      intervals following admission. At each visit, two psychiatrists made consensus
      DSM-IV and ICD-10 diagnoses, based on all available information. Stability was
      discerned as the consistency between diagnoses at the time of discharge and at 12
      month follow up. RESULTS: Forty-eight patients completed follow up. Affective
      psychotic disorders and schizophrenia in both classification systems were highly
      stable. In addition, all patients with DSM-IV brief psychotic disorder and ICD-10
      acute and transient psychotic disorders remained the same at follow up.
      CONCLUSIONS: Affective psychoses and schizophrenia, in line with previous
      findings, remained stable. Diagnoses of brief psychoses were highly stable as
      well; this could reflect a non-relapsing course of acute brief psychoses,
      especially in developing countries.

PMID- 16403138
TI  - Current delivery of infant mental health services: are infant mental health needs
      being met?
AB  - OBJECTIVE: To identify services supporting the well-being of infants and their
      families in an area of South Brisbane, Australia, highlight problems of accessing
      these services and recommend strategies to make them more readily available.
      METHOD: Semistructured interviews were conducted with staff from 18 service
      providers offering antenatal services, or programmes primarily focused on
      children under the age of 2 years and/or their families. The interview aimed to
      identify the precise nature of the services offered, problems encountered in
      providing those services, perceived gaps in services and potential strategies for
      improvement. RESULTS: Services were diverse, provided by a range of different
      professionals, in varying locations (home, community, hospital) and with funding
      from various sources. The major findings were: (i) the fragmentation of services,
      lack of communication between them, and lack of continuity in services from one
      stage of family formation to another; (ii) the shortage of services working with
      the parents and infant together; and (iii) the difficulty of providing services
      for some at-risk populations. CONCLUSIONS: Recommendations included: (i)
      maintaining a range of different services networked through a centralized
      resource/referral centre; (ii) expanding joint mother-infant services and
      providing training for such services; and (iii) supporting outreach services for
      difficult to engage populations.

PMID- 16403139
TI  - Contribution of 'school-link' to an area mental health service.
AB  - OBJECTIVE: To evaluate the contribution of the 'School-Link' initiative to an
      Area Mental Health Service. METHOD: Surveys and focus groups of school and health
      service personnel were conducted to examine the three foci of the School-Link
      initiative, namely prevention, early intervention and service access. RESULTS:
      Improvements witnessed since the commencement of School-Link include an increase
      in the number of evidence-based mental health promotion programmes in schools,
      improvements in the communication between health and education departments,
      improvements in referral patterns and better practices, such as improved
      feedback, in both health and education sectors. School counsellors feel more
      supported in their role by health services and better able to manage certain
      patients. CONCLUSIONS: The actual and potential benefits of School-Link for young
      persons appear considerable. School-Link has provided opportunities for
      communication, upgrading of skills and collaborative work on mental health
      issues, in both education and health settings.

PMID- 16403140
TI  - Challenges of mental health interpreting when working with deaf patients.
AB  - OBJECTIVE: The aim of this present paper is to highlight some of the issues faced
      by therapists and sign language interpreters when working with deaf patients.
      CONCLUSIONS: Key issues include linguistic, interpreting and role challenges, and
      potential threats to the therapeutic alliance. Recommendations are made in
      relation to preparation strategies and training for sign language interpreters
      and therapists.

PMID- 16403141
TI  - Heroes and villains: making sense of the history of psychiatry.
AB  - OBJECTIVE: To review two seemingly contradictory accounts of the history of
      psychiatrists and psychiatry and outline some thoughts on integrating these
      differing views. METHOD: The context of these two accounts is given in a brief
      overview of the historiography of medicine and psychiatry in the nineteenth and
      twentieth centuries with illustrative examples, in particular looking at the
      practically useful distinction between the traditional and social history of
      psychiatry. CONCLUSIONS: Understanding how and why these two currents of
      psychiatric history differ allows one to derive and integrate useful insights
      from both.

PMID- 16403142
TI  - Mrs Hitler and her doctor.
AB  - OBJECTIVE: The doctor who attended the mother of Adolf Hitler in her terminal
      illness has been blamed as a cause of the Holocaust. The medical details recorded
      of this professional relationship are presented and discussed. CONCLUSIONS: Dr
      Bloch's medical care of Mrs Hitler was consistent with the prevailing medical
      practice of the management of fungating breast carcinoma. Indeed, the general
      practitioner's care and attention of the family appear to have been astute and
      supportive. There is nothing to suggest that Dr Bloch's medical care was other
      than competent. Doctors who have the (mis)fortune to professionally attend major
      figures of history may be unfairly viewed, despite their appropriate and adequate
      care.

PMID- 16403143
TI  - Is psychiatry an art or a science? The views of psychiatrists and trainees.
AB  - OBJECTIVE: It is generally considered by many practitioners that psychiatry is an
      art, that is, one of the humanities, as well as being a science. We
      systematically collected the views of practitioners and trainee psychiatrists
      regarding the question 'Is psychiatry an art or a science?' METHOD: Eleven
      supervisors and nine trainees were interviewed and their responses analysed,
      using a qualitative method, the modified framework approach. RESULTS: Several
      themes emerged from the data: that 'art' and 'science' are different; psychiatry
      as a discipline is difficult to define; psychiatry demands a broader range of
      skills than other medical specialties; the relationship of psychology to
      psychiatry; supervisor cynicism to the 'science' of psychiatry; and the 'art' and
      'science' of the assessment process. CONCLUSIONS: The tension that exists within
      the profession's identity as a discipline has important implications for
      teaching, learning, and clinical and research practices.

PMID- 16403149
TI  - Admissions into an acute unit.

PMID- 16403150
TI  - Potential danger associated with stuck capsules.

PMID- 16403151
TI  - Ethical and legal implications of voluntary treatment.

PMID- 16403156
TI  - Programmable multiple pacing configurations help to overcome high left
      ventricular pacing thresholds and avoid phrenic nerve stimulation.
AB  - BACKGROUND: High left ventricular pacing (LVP) thresholds and phrenic nerve
      stimulation (PNS) are common problems with cardiac resynchronization (CRT). Newer
      systems capable of multiple LVP configurations may help overcome these problems
      without the need for reoperation. METHODS: CRT systems capable of multiple LVP
      configurations (Guidant models H155 and H145) were implanted in 43 patients
      (study group). An additional 49 patients (control group) received CRT systems
      (Guidant, Medtronic, Biotronik, St. Jude Medical, various models) lacking this
      feature. RESULTS: Overall, acute high (> or =2.5 V/0.5 ms) LVP thresholds were
      encountered in 13 (30%) of the study group, and 25 (50%) of control group
      patients (P = 0.03). PNS was encountered in 5 (12%) of the study group and 12
      (24%) of control group patients (P = 0.13). All cases of high LVP thresholds and
      PNS in the study group were managed by switching to a different LVP
      configuration, while high thresholds remained in control group patients, and PNS
      was managed by replacing the lead. The CS lead was successfully placed in a
      lateral branch in 95% of study group, compared to only 77% of control group
      patients (P = 0.004). CONCLUSIONS: Multiple LVP configurations were clinically
      useful in a significant number of patients undergoing CRT system implantation by
      helping to overcome high LVP thresholds and PNS, and by providing more
      flexibility in placing the LV lead.

PMID- 16403157
TI  - Determinants of mortality in patients undergoing cardiac resynchronization
      therapy: baseline clinical, echocardiographic, and angioscintigraphic evaluation
      prior to resynchronization.
AB  - BACKGROUND: In dilated cardiomyopathy (DCM) patients (pts) with cardiac
      resynchronization therapy (CRT) for ventricular dyssynchrony, long-term
      predictors of mortality and morbidity remain poorly investigated. METHOD AND
      RESULTS: We reviewed data of 102 pts, 68 +/- 10 years, NYHA Class II-IV (14 Class
      II, 67 Class III, 21 Class IV), who benefited from CRT (69 CRT, 33 CRT-ICD).
      Fifty-two patients had an ischemic DCM, 36 a previously implanted conventional
      PM/ICD, 29 a permanent atrial fibrillation, and 19 needed dobutamine in the month
      preceding implant. QRS duration was 187 +/- 35 ms, left ventricular end-diastolic
      diameter 72 +/- 10 mm, mitral regurgitation severity 1.9 +/- 0.8, echographic
      aorto-pulmonary electromechanical delay 61.5 +/- 25 ms and septo-lateral left
      intraventricular delay 86 +/- 56 ms, pulmonary artery pressure (PAP) 43 +/- 11
      mmHg, angioscintigraphic left ventricular ejection fraction (EF) 20 +/- 9%, and
      right ventricular EF 30.5 +/- 14%. Over a mean follow-up of 23 +/- 20 months, 26
      pts died (18 heart failures (HFs), 1 arrhythmic storm, 7 noncardiac deaths).
      Positive univariate predictors of death from any cause were NYHA Class IV (P <
      0.001), and need for dobutamine the month preceding CRT (P < 0.008), while use of
      beta-blocking agents (P < 0.08) and left ventricular EF (P < 0.09) were negative
      ones. NYHA Class IV was the only independent predictor at multivariate analysis
      (P < 0.01). Survival at 24 months was 85% in Class II, 80% in Class III, and 37%
      in Class IV (II vs III, P = ns; III vs IV, P < 0.001). When using a composite
      endpoint of death from any cause and unplanned rehospitalization for a major
      cardiovascular event, there were 48 events (14 HF deaths, 3 noncardiac deaths, 26
      HF rehospitalizations, 2 paroxysmal atrial fibrillation, 2 sustained ventricular
      tachycardia, 1 nonfatal pulmonary embolism). Predictors of death from any
      cause/unplanned rehospitalization for a major cardiovascular event in the follow
      up were NYHA Class IV (P < 0.001), need for dobutamine during the month preceding
      CRT (P < 0.002), and PAP (<0.02). NYHA Class IV was the only independent
      predictor at multivariate analysis (P < 0.05). Event-free proportion at 24 months
      was 70% in Class II, 64% in Class III, and 37% in Class IV (II vs III, P = ns;
      III vs IV, P < 0.01). When considering determinants of mortality only in NYHA
      Class IV patients, no variable was significantly correlated to mortality. Need
      for dobutamine during the last month preceding CRT did not add an adjunctive
      mortality risk. CONCLUSION: Baseline NYHA Class IV at implantation appears as the
      most important determinant of a poor clinical outcome in terms of both mortality
      and morbidity. No predictive criteria seem available for NYHA Class IV patients,
      in order to discriminate who will die after CRT and who will not. NYHA Class IV
      strongly influences the clinical outcome, suggesting that, in future studies
      planned on mortality and rehospitalization as major endpoints, baseline NYHA
      Class IV should be separately taken into account.

PMID- 16403158
TI  - Does a gender difference in response to cardiac resynchronization therapy exist?
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has a beneficial effect on
      clinical symptoms, exercise capacity, and systolic left ventricular (LV)
      performance in patients with heart failure. The aim of the current study was to
      evaluate whether a gender difference exists in response to CRT. METHODS:
      Consecutive patients with end-stage heart failure (New York Heart Association,
      NYHA, class III-IV), LV ejection fraction (LVEF) < or =35%, QRS duration >120 ms,
      and left bundle branch block configuration underwent CRT. At baseline and 6
      months post-CRT, clinical and echocardiographic parameters were evaluated; follow
      up was obtained up to 5 years. The effects of CRT were compared between women and
      men. RESULTS: The study population comprised 137 men and 36 women (mean age 66 +/
      11 years). No differences in baseline characteristics were observed except that
      nonischemic cardiomyopathy was more frequent in women than men (67% vs 38%, P <
      0.05). In all patients, clinical and echocardiographic parameters improved
      significantly at 6-month follow-up. The magnitude of improvement in different
      parameters was similar between women and men, e.g., the improvement in NYHA Class
      was 0.9 +/- 0.6 in women and 1.0 +/- 0.7 in men (NS) and the increase in LVEF was
      8 +/- 8% in women as compared to 7 +/- 9% in men (NS). The percentage of
      individual responders was not different between women and men (76% vs 80%, NS)
      and 2-year survival was comparable for women and men (84% vs 80%, NS).
      CONCLUSION: No gender differences were observed in response to CRT and long-term
      survival after CRT.

PMID- 16403160
TI  - Different patterns of the fall of impedance as the result of heating during
      ostial pulmonary vein ablation: implications for power titration.
AB  - BACKGROUND: A variety of strategies have been proposed to avoid the risks of
      pulmonary vein ablation for atrial fibrillation. The fall of impedance during
      radiofrequency catheter ablation can be used as a real time measure of tissue
      heating. The aim of this study was to analyze the impedance fall during ostial
      pulmonary vein ablation and to evaluate whether adjusting power to the fall of
      impedance may contribute to a reduction of the risk of complications. METHODS:
      Analysis of biophysical parameters of ablation and determination of ostial
      diameters during follow-up were performed in 70 patients undergoing impedance
      guided segmental ostial pulmonary vein ablation. Repeat radiographic angiography,
      local electrograms, and baseline impedance were the criteria to define the
      position of the 4-mm electrode tip at atrial sites or inside the proximal
      pulmonary veins. RESULTS: Energy application inside the proximal pulmonary veins
      led to an increased impedance fall inside the first 5-10 mm of the pulmonary
      veins (1.1 +/- 0.5 Omega/W) as compared to ablation at atrial sites (0.7 +/- 0.3
      Omega/W) (P < 0.01). The analysis of temperature and impedance fall during ostial
      ablation demonstrated an increased impedance fall with heating at sites inside
      the proximal pulmonary veins (1.5 +/- 0.6 Omega/ degrees C) as compared to atrial
      sites (1.2 +/- 0.5 Omega/ degrees C) (P < 0.001). The regression lines analyzing
      these correlations indicated that adjusting power to a maximum impedance fall of
      20 Omega would limit heating at pulmonary venous sites to lower temperatures
      (average maximum temperature: 48 degrees C) than at atrial sites (average maximum
      temperature: 63 degrees C). The ablation strategy used for segmental ostial
      ablation in 70 patients, which involved power limitation to a maximum impedance
      fall of 20 Omega, allowed isolation of 89% of targeted pulmonary veins with a low
      rate of impedance rises (0.3% of applications). No pulmonary vein stenoses >30%
      were detected by follow-up computed tomography analysis. CONCLUSIONS: An
      increased impedance fall as the result of heating during ostial ablation was
      found inside the proximal pulmonary veins as compared to atrial sites. Adjusting
      power to the fall of impedance during segmental ostial pulmonary vein ablation
      contributes to the prevention of overheating inside the pulmonary veins and may
      lower the risk of coagulum formation and pulmonary vein stenosis.

PMID- 16403159
TI  - The role of swab and tissue culture in the diagnosis of implantable cardiac
      device infection.
AB  - BACKGROUND: The isolation of a pathogen is vital in the diagnosis and treatment
      of a device infection. A swab culture, despite poor sensitivity, is the most
      common method used in specimen collection. OBJECTIVE: To determine the relative
      value of swab and tissue specimen cultures in patients with implantable cardiac
      pacemakers and defibrillators. DESIGN: Prospective patient cohort study. SETTING:
      A 1,000-bed tertiary referral center in Cleveland, Ohio. PATIENTS: Consecutive
      patients with implantable cardiac pacemaker or defibrillator presenting for lead
      extraction from October 1, 2000 to March 31, 2001. METHODS: Tissue and swab
      cultures were prospectively collected during pacemaker and implantable
      defibrillator surgeries that required lead extraction. Clinical manifestations,
      microbiology, and echocardiographic data were recorded in patients with and
      without a clinical diagnosis of device system infection. RESULTS: Seventy-one
      patients with implantable pacemaker (n = 49, 69%), implantable defibrillator (n =
      18, 25%), or both devices (n = 4, 6%) requiring lead extraction had pocket swab
      and tissue cultures for analysis. Infection was evident clinically in 35 (49%) of
      the patients and absent in the remainder. The most common bacteria isolated were
      coagulase-negative Staphylococcus (37%) and Staphylococcus aureus (10%). Patients
      with clinical infection had positive cultures more frequently (P = 0.002) by
      pocket tissue culture (n = 24, 69%) than by swab culture (n = 11, 31%). However,
      patients without clinical infections had positive cultures at similar rates by
      pocket tissue culture (n = 10, 28%) and by swab culture (n = 8, 22%; P = 0.48).
      Patients without clinical infection were not treated with other than
      perioperative antibiotics, and did not develop clinical infections. CONCLUSION:
      Pocket tissue cultures are more effective than pocket swab cultures for the
      isolation and identification of the infectious pathogens in cardiac device
      infections. Positive cultures by pocket swab or tissue cultures in the absence of
      clinical signs and symptoms of infection does not imply infection or the need for
      specific therapy.

PMID- 16403161
TI  - Usefulness of atrial fibrillation burden as a predictor for success of pulmonary
      vein isolation.
AB  - BACKGROUND: The definition of symptomatic improvement after pulmonary vein
      isolation (PVI) is controversial. We assessed primarily the usefulness and
      predictive accuracy (PA) of AF (atrial fibrillation) burden (AFB) within the
      first 3 months after the procedure as an early predictor for curative success as
      well as reduction of symptoms. METHODS: We studied 100 pts (62 men, mean age: 54
      +/- 9 years, LVEF: 57 +/- 9%, paroxysmal AF, 85, persistent AF, 15) who underwent
      PVI. RF ablation was used in 63 patients. The combination of cryoablation and RF
      (Hybrid therapy) was used in the remaining 37 patients, in 19 patients of whom
      additionally linear lesions were performed. All patients were followed up 3
      months after PVI (the blanking period) and every 3 months thereafter. The
      significance of early recurrence of AF (ERAF) was separately analyzed for RF and
      for hybrid therapy arm. Quality of life (QoL) was assessed using the physical
      composite summary score (PCS) and mental composite summary score (MCS). AFB was
      dichotomized at: 0, 0.5, 1, 6, 12, and 24 hours. RESULTS: ANOVA revealed
      significant differences between PCS at baseline and after PVI in patients without
      recurrence and with those with postablation AFB <12 hours. There was no
      difference between PCS in patients with AFB > or =12 hours within a 3 months
      interval and PCS at baseline. ERAF occurred in 35% of patients (16 patients, AFB
      > or =12 hours). Symptomatic ERAF occurred in 29 patients (17 patients AFB > or
      =12 hours). After the blanking period, documented AF recurrence was found in 50
      patients (17 patients, AFB > or =12 hour). Symptomatic late recurrence was found
      in 47 patients (31 patients with AFB > or =12 hours). Absence of ERAF was
      revealed to be predictive for long-term success and symptomatic ERAF was found to
      be predictive for symptomatic AF recurrence (P <0.0001). CONCLUSION: AF
      recurrence with AFB > or =12 hours within 3 months is associated with a missed
      improvement of QoL. Symptomatic ERAF predicts recurrence independently of
      therapy.

PMID- 16403162
TI  - Ten year follow-up after radiofrequency catheter ablation for atrioventricular
      nodal reentrant tachycardia in the early days forever cured, or a source for new
      arrhythmias?
AB  - BACKGROUND: Radiofrequency (RF) catheter ablation is highly effective with a low
      complication rate. However, lesions created by RF energy are irreversible,
      inhomogeneous, and therefore potentially proarrhythmic. OBJECTIVES: The aim of
      this study was to examine the magnitude and importance of long-term proarrhythmic
      effects of RF energy. METHODS AND RESULTS: Between 1991 and 1995, 120 patients
      underwent RF ablation for atrioventricular nodal reentrant tachycardia (AVNRT).
      Patient data were collected by contacting patients and/or filling out a
      questionnaire, and medical files were screened for recurrent, documented
      arrhythmias, pharmacological treatment, and repeated EP study. Referring
      cardiologists were asked about recurrences of tachyarrhythmias. Fourteen patients
      (11%) were lost to follow-up. During a mean follow-up of 10 years, six patients
      died. Recurrences of AVNRT were not any more observed after 3 years after
      ablation. A total of 29 patients (24%) suffered from new arrhythmias, 6 from type
      1 atrial flutter, 6 from atrial tachycardia, 9 from atrial fibrillation, and
      finally 16 from symptomatic premature atrial contractions (PACs), needing medical
      treatment or a combination of these arrhythmias. Nine patients underwent
      pacemaker implantation, 4 after developing procedural atrioventricular (AV)
      conduction disturbances, 2 after His ablation for permanent atrial fibrillation,
      1 patient for sick sinus syndrome, and another 2 patients after developing late
      AV block, respectively, 7 and 9 years after ablation. CONCLUSION: During long
      term follow-up after RF ablation for AVNRT, no AVNRT recurrences were observed,
      but 29 patients (24%) suffered from new arrhythmias or late AV block. This
      potential proarrhythmic effect of RF energy promotes the application of
      alternative energy sources for ablative therapies for cardiac arrhythmias.

PMID- 16403163
TI  - Heart rate variability during sleep in patients with vasovagal syncope.
AB  - BACKGROUND: There are a few studies showing no significant heart rate variability
      (HRV) over a 24-hour period in vasovagal syncope (VVS) patients, but no research
      has examined HRV and its sympathetic and parasympathetic components during rapid
      eye movement (REM) and non-REM sleep. The authors hypothesized that REM sleep
      might be a critical state in which VVS patients would show abnormal responses.
      OBJECTIVES: To analyze the sympathetic and parasympathetic components of HRV
      during REM and SWS in patients with VVS compared to normal subjects, and in
      patients with positive HUTT compared to negative ones. METHODS: Thirty-seven VVS
      patients and 20 normal age-matched controls were submitted to polysomnography
      with 24-hour Holter monitoring to assess HRV. Time and frequency domain
      techniques were carefully performed for 24 hours and during Stages 3 and 4 of REM
      and non-REM sleep. Variation of sympathetic activity index (VSAI) was defined as
      the difference in the low frequency (LF) component of HRV between REM and Stages
      3 and 4 of non-REM sleep. An analysis of variance was performed to compare
      patients and controls; patients with positive and negative head-up tilt testing.
      RESULTS: The LF component was lower in syncope compared to normal patients
      (1,769.54 +/- 1,738.17, 3,225.37 +/- 2,585.05, respectively, P = 0.03). There was
      a significant decrease in VSAI in the syncope group compared to the control group
      (-539.39 +/- 1,930.78, 1,268.10 +/- 2,420.20, respectively, P = 0.01). The other
      sleep variables analyzed including very LF, high frequency, low frequency/high
      frequency and time domain parameters did not reach statistical significance.
      Syncope patients also showed an increase in slow wave sleep (28.2 +/- 10.5, 19.7
      +/- 7.8, P = 0.01). CONCLUSIONS: VVS patients exhibited sympathetic suppression
      during REM sleep. Possible mechanisms are discussed in this article.

PMID- 16403164
TI  - Beat-to-beat cycle length variation during narrow QRS complex tachycardia: what
      is the mechanism?

PMID- 16403165
TI  - Alternating preventricular and postventricular atrial far-field sensing by a dual
      chamber cardioverter defibrillator.

PMID- 16403166
TI  - Advanced ICD troubleshooting: Part I.

PMID- 16403167
TI  - Ventricular fibrillation in two cases with dilated cardiomyopathy and mechanical
      alternans.
AB  - Clinical implication of mechanical alternans is yet unclear. It may suggest the
      risk for sudden death in patients with chronic heart failure. Two cases with
      dilated cardiomyopathy showed mechanical alternans during diagnostic cardiac
      catheterization. They suddenly died due to ventricular fibrillation before the
      induction of beta-blocker therapy. Patients with mechanical alternans should be
      treated under intense monitoring until the induction of beta-blocker therapy.

PMID- 16403168
TI  - Atrial fibrillation and recurrent ventricular fibrillation during hypokalemia in
      Brugada syndrome.
AB  - A 41-year-old man with Brugada syndrome (BS) and no previous episodes of aborted
      sudden death or syncope referred to local emergency room for an episode of
      symptomatic atrial fibrillation. Blood chemistry results showed hypokalemia (2.9
      mEq/L). The other parameters were within the normal range. After few minutes, an
      episode of ventricular fibrillation treated with biphasic DC shock 150 J
      occurred. In successive 2 hours, the patient experienced recurrent episodes of
      ventricular tachycardia and fibrillation. Each biphasic DC shock 150 J was
      effective to restore sinus rhythm. No further episodes occurred after
      normalization of serum levels of potassium. Before discharge, an implantable
      cardioverter defibrillator was inserted to prevent sudden cardiac death.
      Hypokalemia increases the risk of arrhythmic events in BS.

PMID- 16403169
TI  - Sustained ventricular tachycardia following alcohol septal ablation for
      hypertrophic obstructive cardiomyopathy.
AB  - A 49-year-old man with a history of hypertrophic obstructive cardiomyopathy
      (HOCM) presented in sustained monomorphic ventricular tachycardia (SMVT) 8 days
      post-alcohol septal ablation. A dual chamber implantable cardioverter
      defibrillator ICD was implanted and the patient experienced another episode of VT
      3 weeks later, which was terminated by an ICD shock. This case demonstrates
      probable scar-induced reentrant VT post-alcohol septal ablation, a likely rare
      but hypothesized complication of this procedure.

PMID- 16403170
TI  - Atypical left bundle branch block in dilative "burned-out" phase of hypertrophic
      cardiomyopathy.
AB  - We present the case of a 70-year-old man admitted in congestive heart failure.
      The patient was diagnosed 22 years ago of hypertrophic cardiomyopathy (HC). ECG
      showed a very peculiar and pathological form of left bundle branch block (LBBB).
      2D-echocardiogram revealed a dilated left ventricle (LV) and ejection fraction of
      25%. LV remodeling represents an important component of the pathophysiology of HC
      and, paradoxically, some patients develop LV wall thinning, systolic dysfunction,
      and congestive heart failure (in the absence of coronary artery disease). This
      evolution is designated as "end-stage" or "burned-out"phase. We present this rare
      LBBB and his pathological evolution along the time as unique manifestation of
      this "burned-out" phase. The mechanism of this wall thinning remains unclear but
      changes in ECG may alert us about it.

PMID- 16403171
TI  - Pacemaker auto-interference by thoracic impedance measurement for the rate
      response function.
AB  - This report describes two cases of pacemaker auto-interference caused by thoracic
      impedance measurements for the rate response function of a dual chamber
      pacemaker. Mechanisms of this phenomenon and reprogramming strategies are
      discussed.

PMID- 16403172
TI  - Re: Validation of dual-chamber pacemaker diagnostic data using dual-channel
      stored electrograms.

PMID- 16403174
TI  - Review and meta-analysis of the phenomenology and clinical characteristics of
      mania in children and adolescents.
AB  - OBJECTIVE: Using predetermined criteria for study quality and methods, a
      literature review and meta-analysis of seven reports about pediatric bipolar
      disorder (BPD) was conducted to determine if there is a consistent picture of the
      phenomenology and clinical characteristics of BPD in children and adolescents.
      METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania,
      BPD, children and adolescents, and was limited to published articles in peer
      reviewed journals. Seven reports were selected that met the following criteria: a
      systematic method for the elicitation and reporting of symptoms and clinical
      characteristics of subjects; subjects were interviewed by a trained researcher or
      clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for
      categorization; a consensus method for the establishment of the diagnosis of BPD.
      RESULTS: Most DSM-IV symptoms of mania were common in the children and
      adolescents with BPD with the most common symptoms being increased energy,
      distractibility, and pressured speech. On average, four of five bipolar cases
      also showed threshold levels of irritable mood and grandiosity, and more than 70%
      of all cases showed elated/euphoric mood, decreased need for sleep, or racing
      thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of
      bipolar cases demonstrated flight of ideas, and slightly more than one-third
      showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture
      that emerges is that of children or adolescents with periods of increased energy
      (mania or hypomania), accompanied by distractibility, pressured speech,
      irritability, grandiosity, racing thoughts, decreased need for sleep and
      euphoria/elation.

PMID- 16403175
TI  - Bipolar disorder in children and adolescents: international perspective on
      epidemiology and phenomenology.
AB  - OBJECTIVE: There is considerable skepticism outside the US over the prevalence of
      pediatric bipolar disorder (BD). We wished to evaluate the epidemiology of BD in
      children and adolescents in non-US samples. METHOD: We reviewed studies on the
      prevalence of BD in children and adolescents in international samples. We also
      describe our sample of 27 children with BD at the University of Navarra. RESULTS:
      There are important and frequently overlooked differences in the definition of BD
      between the International Classification of Diseases 10th edition (ICD-10) and
      DSM-IV and methodological differences in epidemiological studies that may
      partially explain international differences in prevalence of pediatric BD. The
      prevalence of bipolar spectrum disorder in young adults in Switzerland is 11%. In
      Holland the 6-month prevalence of mania in adolescents was 1.9% and of hypomania
      0.9%. Only 1.2% of hospitalized youth (<15 years) in Denmark and 1.7% of
      adolescents in Finland had BD. In our clinic, the prevalence of DSM-IV BD in
      children 5-18 years old is 4%, and of any mood disorders 27%. There are also data
      from Brazil, India and Turkey with varying results. CONCLUSION: Relative lack of
      data, ICD-10 and DSM-IV differences in diagnostic criteria, different levels of
      recognition of Child and Adolescent Psychiatry as a true specialty in Europe,
      clinician bias against BD, an overdiagnosis of the disorder in USA and/or a true
      higher prevalence of pediatric BD in USA may explain these results. US
      International differences may be a methodological artifact and research is needed
      in this field.

PMID- 16403176
TI  - Comparing diagnostic checklists for pediatric bipolar disorder in academic and
      community mental health settings.
AB  - OBJECTIVES: To compare six promising mania measures, the Parent Mood Disorder
      Questionnaire (P-MDQ), the Adolescent self-report MDQ, the 10-item short form of
      the Parent General Behavior Inventory (PGBI-SF10), the 28-item Adolescent General
      Behavior Inventory (AGBI), the Parent Young Mania Rating Scale (P-YMRS), and the
      adolescent YMRS, in a demographically diverse outpatient sample. METHODS:
      Participants were 262 outpatients (including 164 males and 131 African-Americans)
      presenting to either an academic medical center (n = 153) or a community mental
      health center (n = 109). Diagnoses were based on semi-structured interviews with
      the parent and then youth sequentially. RESULTS: Ninety youths (34%) met criteria
      for a bipolar spectrum disorder. Parent measures yielded Areas Under the Receiver
      Operating Curve (AUROC) values of 0.81 for the PGBI-SF10 to 0.66 for the P-YMRS.
      Adolescent report measures performed significantly less well, with AUROCs ranging
      from 0.65 to 0.50. There were no significant differences in the diagnostic
      performance of the measures across the sites or by racial groups, although the
      reliability of measures tended to be lower in the urban community mental health
      site. The PGBI-SF10 made a significant contribution to logistic regression models
      examining all combinations of the instruments. The P-MDQ added information in the
      younger age group, and no measure improved classification of bipolar cases after
      controlling for the PGBI-SF10 in the older age group. DISCUSSION: Results
      replicate previous findings that, in decreasing order of efficiency, the PGBI
      SF10, P-MDQ, and P-YMRS significantly discriminate bipolar from non-bipolar cases
      in youths aged 5-18; and they appear robust in a demographically diverse
      community setting. Adolescent self-report measures are significantly less
      efficient, sometimes performing no better than chance at detecting bipolar cases.

PMID- 16403177
TI  - The CBCL predicts DSM bipolar disorder in children: a receiver operating
      characteristic curve analysis.
AB  - BACKGROUND: No clear consensus has been reached yet on how best to characterize
      children who suffer from pediatric bipolar disorder (PBD). The CBCL-PBD profile
      on the Child Behavior Checklist (CBCL) has been consistently reported showing
      deviant findings on the Attention Problems, Aggressive Behavior, and Anxious
      Depressed subscales. AIM: To examine the sensitivity and specificity of the
      proposed CBCL-PBD profile for determining DSM diagnosis of PBD. METHODS: We
      applied receiver operating characteristic (ROC) curve analysis to data from 471
      probands from two family studies of attention-deficit hyperactivity disorder and
      their 410 siblings. RESULTS: The CBCL-PBD score demonstrated an area under the
      curve (AUC) of 0.97 for probands and 0.82 for siblings for current diagnosis of
      PBD, suggesting that the CBCL-PBD provided a highly efficient way of identifying
      subjects with a current diagnosis of PBD in this sample. CONCLUSIONS: These
      findings suggest that the CBCL-PBD may provide a highly efficient way of
      screening for childhood bipolar disorder.

PMID- 16403179
TI  - Using affect-modulated startle to study phenotypes of pediatric bipolar disorder.
AB  - OBJECTIVES: Affective neuroscience research that investigates core symptoms of
      pediatric bipolar disorder (PBD) may be effective in differentiating PBD
      phenotypes. The current study used affect-modulated startle to examine potential
      differences in reactivity to emotional stimuli (reward and punishment) in narrow
      and broad phenotype PBD and controls. METHODS: Thirty children meeting DSM-IV
      bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes
      with elevated/expansive mood), 19 children meeting criteria for severe mood
      dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity,
      and hyperarousal), and 19 controls completed a lottery startle paradigm involving
      reward (money) and punishment (loud noise). Startle probes were presented during
      anticipation of the emotional stimulus, immediately following the presentation of
      the stimulus, or during return to baseline following the stimulus. RESULTS: By
      self-report, patients and controls found the putative punishment to be preferable
      to the neutral condition. In the reward condition, patient samples reported
      greater arousal than did controls, but no between-group differences were found on
      the magnitude of startle response during the reward, punishment, or neutral
      conditions. CONCLUSIONS: The failure to find differences in affect-modulated
      startle between control children and those with narrow or broad PBD phenotypes
      speaks to the methodological challenges associated with studying reward
      mechanisms in PBD. Alternative paradigms that focus on different aspects of
      reward mechanisms are discussed.

PMID- 16403178
TI  - History of suicide attempts in pediatric bipolar disorder: factors associated
      with increased risk.
AB  - BACKGROUND: Despite evidence indicating high morbidity associated with pediatric
      bipolar disorder (BP), little is known about the prevalence and clinical
      correlates of suicidal behavior among this population. OBJECTIVE: To investigate
      the prevalence of suicidal behavior among children and adolescents with BP, and
      to compare subjects with a history of suicide attempt to those without on
      demographic, clinical, and familial risk factors. METHODS: Subjects were 405
      children and adolescents aged 7-17 years, who fulfilled DSM-IV criteria for BPI
      (n = 236) or BPII (n = 29), or operationalized criteria for BP not otherwise
      specified (BP NOS; n = 140) via the Schedule for Affective Disorders and
      Schizophrenia for School-Aged Children. As part of a multi-site longitudinal
      study of pediatric BP (Course and Outcome of Bipolar Youth), demographic,
      clinical, and family history variables were measured at intake via clinical
      interview with the subject and a parent/guardian. RESULTS: Nearly one-third of BP
      patients had a lifetime history of suicide attempt. Attempters, compared with non
      attempters, were older, and more likely to have a lifetime history of mixed
      episodes, psychotic features, and BPI. Attempters were more likely to have a
      lifetime history of comorbid substance use disorder, panic disorder, non-suicidal
      self-injurious behavior, family history of suicide attempt, history of
      hospitalization, and history of physical and/or sexual abuse. Multivariate
      analysis found that the following were the most robust set of predictors for
      suicide attempt: mixed episodes, psychosis, hospitalization, self-injurious
      behavior, panic disorder, and substance use disorder. CONCLUSIONS: These findings
      indicate that children and adolescents with BP exhibit high rates of suicidal
      behavior, with more severe features of BP illness and comorbidity increasing the
      risk for suicide attempt. Multiple clinical factors emerged distinguishing
      suicide attempters from non-attempters. These clinical factors should be
      considered in both assessment and treatment of pediatric BP.

PMID- 16403180
TI  - Declarative memory impairment in pediatric bipolar disorder.
AB  - OBJECTIVES: Impaired verbal declarative memory has been proposed as a trait
      marker for adult bipolar disorder. However, similar impairments in juvenile-onset
      bipolar disorder have not been yet documented. Here, we assessed declarative
      memory in a large sample of clinically well-characterized children with bipolar
      disorder. METHODS: Forty-one children and adolescents with bipolar disorder [21
      bipolar I disorder (BP-I), 10 bipolar II disorder (BP-II), and 10 bipolar
      disorder, not otherwise specified (BP-NOS)] and 17 demographically matched
      healthy participants completed a standardized learning and memory test. RESULTS:
      BP-I children recalled and recognized significantly fewer words than healthy
      subjects, whereas children with BP-II and BP-NOS did not differ from controls.
      However, individuals with BP-NOS made more perseverative errors and intrusions
      than the other groups. Severity of mood symptomatology was not associated with
      memory performance in any bipolar subtype. CONCLUSIONS: Findings suggest that
      declarative memory impairments in juvenile BP-I are similar to those seen in the
      adult form of the illness. These impairments do not appear to be secondary to
      clinical state; rather, they may reflect trait-related impairments. Distinct
      performance patterns in BP-I, BP-II, and BP-NOS suggest that the broadly defined
      phenotype is significantly heterogeneous, and may not be informative for
      pathogenetic investigations of bipolar disorder.

PMID- 16403181
TI  - Cortical gray matter differences identified by structural magnetic resonance
      imaging in pediatric bipolar disorder.
AB  - OBJECTIVE: Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD)
      have investigated the entire cerebral cortex. Cortical gray matter (GM) volume
      deficits have been reported in some studies of adults with BPD; this study
      assessed the presence of such deficits in children with BPD. METHODS: Thirty-two
      youths with DSM-IV BPD (mean age 11.2 +/- 2.8 years) and 15 healthy controls (HC)
      (11.2 +/- 3.0 years) had structured and clinical interviews, neurological
      examinations, neurocognitive testing, and MRI scanning on a 1.5 T GE Scanner.
      Image parcellation divided the neocortex into 48 gyral-based units per
      hemisphere, and these units were combined into frontal (FL), temporal (TL),
      parietal (PL), and occipital (OL) lobe volumes. Volumetric differences were
      examined using univariate linear regression models with alpha = 0.05. RESULTS:
      Relative to controls, the BPD youth had significantly smaller bilateral PL, and
      left TL. Analysis of PL and TL gyri showed significantly smaller volume in
      bilateral postcentral gyrus, and in left superior temporal and fusiform gyri,
      while the parahippocampal gyri were bilaterally increased in the BPD group.
      Although the FL overall did not differ between groups, an exploratory analysis
      showed that the right middle frontal gyrus was also significantly smaller in the
      BPD group. CONCLUSIONS: Children with BPD showed deficits in PL and TL cortical
      GM. Further analyses of the PL and TL found differences in areas involved in
      attentional control, facial recognition, and verbal and declarative memory. These
      cortical deficits may reflect early age of illness onset.

PMID- 16403182
TI  - Preliminary evidence for persistent abnormalities in amygdala volumes in
      adolescents and young adults with bipolar disorder.
AB  - OBJECTIVES: Abnormalities in volumes of the amygdala have been reported
      previously in adolescents and adults with bipolar disorder (BD). Several studies
      have reported reduced volumes in adolescents with BD; however, both decreases and
      increases in volumes have been reported in adults with BD. Understanding of
      potential developmental contributions to these disturbances in morphology of the
      amygdala has been limited by the absence of longitudinal data in persons with BD.
      Here we use a within-subject longitudinal design to investigate whether amygdala
      volume abnormalities persist in adolescents and young adults with BD over a time
      interval of approximately 2 years. METHODS: Participants included 18 adolescents
      and young adults: 10 participants with BD I and 8 healthy comparison
      participants. Amygdala volumes were measured on high-resolution magnetic
      resonance imaging scans acquired twice for each subject over intervals of
      approximately 2 years. Amygdala volumes were the dependent measures in a mixed
      model statistical analysis to compare amygdala volumes between groups over time
      while covarying for total brain volume. RESULTS: Amygdala volumes were
      significantly smaller in adolescents and young adults with BD compared with
      healthy participants (p = 0.018). The effect of time was not significant.
      CONCLUSIONS: Although the sample size is modest, this study provides preliminary
      evidence to support the presence of decreased amygdala volumes in adolescents and
      young adults with BD that persist during this developmental epoch.

PMID- 16403183
TI  - Comorbid ADHD is associated with altered patterns of neuronal activation in
      adolescents with bipolar disorder performing a simple attention task.
AB  - OBJECTIVES: Bipolar disorder is increasingly recognized as a significant source
      of psychiatric morbidity in children and adolescents. Younger bipolar patients
      symptomatically differ from adults, and frequently present with comorbid
      disorders, particularly attention-deficit hyperactivity disorder (ADHD). The
      neurophysiological relationship between these two disorders, however, remains
      unclear. In this study we utilized functional magnetic resonance imaging (fMRI)
      to compare activation patterns during performance of a simple attention task
      between bipolar adolescents with and without ADHD. METHODS: Eleven bipolar
      adolescents with comorbid ADHD and 15 bipolar adolescents without comorbidity
      were recruited to participate in fMRI scans. A single-digit continuous
      performance task alternated with a control task in a block-design paradigm.
      between-group comparisons were made using voxel-by-voxel analysis. Follow-up
      correlations were made between performance and activation. RESULTS: Group
      performance did not significantly differ in percentage correct (p = 0.36) or
      discriminability (p = 0.11). ADHD comorbidity was associated with less activation
      in the ventrolateral prefrontal cortex (Brodmann 10) and anterior cingulate, and
      greater activation in posterior parietal cortex and middle temporal gyrus.
      Comorbid ADHD was associated with substantial differences in patterns of
      correlation between performance and voxel-by-voxel activation. CONCLUSIONS: Our
      findings suggest that comorbid ADHD in bipolar adolescents is associated with
      activation of alternative pathways during performance of a simple attention task.
      The pattern of differences suggests that bipolar adolescents with comorbid ADHD
      demonstrate decreased activation of prefrontal regions, compared with bipolar
      adolescents without ADHD, and preferentially recruit portions of posterior
      parietal and temporal cortex.

PMID- 16403184
TI  - N-acetylaspartate levels in bipolar offspring with and at high-risk for bipolar
      disorder.
AB  - OBJECTIVES: Studies have reported decreased N-acetylaspartate (NAA) in
      dorsolateral prefrontal cortex (DLPFC) of adults and children with bipolar
      disorder (BD), suggesting decreased neuronal density in this area. However, it is
      unclear if this finding represents neurodegeneration after or a trait marker
      present before BD onset. To address this question, we used proton magnetic
      resonance spectroscopy ((1)H-MRS) to compare DLPFC levels of NAA among bipolar
      offspring with early-onset BD, bipolar offspring with subsyndromal symptoms of BD
      and healthy children. METHODS: Participants were 9-18 years old, and included 60
      offspring of parents with bipolar I or II disorder (32 with BD and 28 with
      subsyndromal symptoms of BD), and 26 healthy controls. (1)H-MRS at 3 T was used
      to study 8-cm(3) voxels placed in left and right DLPFC. RESULTS: There were no
      significant group differences in mean right or left DLPFC NAA/Cr ratios.
      Exploratory analyses of additional metabolites (myoinositol, choline) also
      yielded no significant group differences. NAA/Cr ratios were not correlated with
      age, duration of illness, or exposure to lithium or valproate. CONCLUSIONS: Our
      findings suggest that DLPFC NAA/Cr ratios cannot be used as a trait marker for
      BD. Although we did not find decreased DLPFC NAA/Cr ratios in children and
      adolescents with BD, it is still possible that such levels begin to decrease
      after longer durations of illness into adulthood. Longitudinal neuroimaging
      studies of patients with BD accounting for developmental and treatment factors
      are needed to further clarify the neurodegenerative aspects of BD.

PMID- 16403185
TI  - Family, twin, adoption, and molecular genetic studies of juvenile bipolar
      disorder.
AB  - Juvenile bipolar disorder (JBD) has been a subject of significant research and
      debate. Phenotypic differences between JBD and adult-onset bipolar disorder have
      led researchers to question whether or not similar neuropathologic mechanisms
      will be found. While much is known about the genetic and environmental
      contributions to the adult-onset phenotype, less is known about their
      contributions to JBD. Here, we review family, twin, adoption, and molecular
      genetic studies of JBD. Behavioral genetic data suggest both genetic and
      environmental contributions to JBD, while molecular genetic studies find linkage
      to age of onset of bipolar disorder to chromosomes 12p, 14q, and 15q.
      Additionally, changes associated with symptom age of onset have been recently
      reported in the brain-derived neurotrophic factor (BDNF) and glycogen synthase
      kinase 3-beta (GSK3-beta) genes. We contend that further progress in discovering
      the precise genetic and environmental contributions to JBD may depend on advances
      in phenotypic refinement, an increased appreciation of comorbid conditions, and
      more investigation of the longitudinal course of the disorder.

PMID- 16403186
TI  - Are the arginine vasopressin V1a receptor microsatellites related to
      hypersexuality in children with a prepubertal and early adolescent bipolar
      disorder phenotype?
AB  - OBJECTIVE: To examine family-based transmission of the number of 5' flanking
      arginine vasopressin V1a receptor (AVPR1A) microsatellites, which include
      [(GATA)(14)] and complex [(CT)(4)-TT-(CT)(8)-(GT)(24)] repeats, in probands with
      a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP).
      Preferential transmission of the number of AVPR1A microsatellite repeats to
      hypersexual and uninhibited people-seeking probands was hypothesized, based on
      reports from preclinical work in the literature. METHODS: Probands were 83
      participants in an ongoing controlled study of PEA-BP. The PEA-BP phenotype was
      defined by DSM-IV mania with at least one of the cardinal symptoms of mania
      (elation and/or grandiosity) to avoid diagnosing mania only by symptoms that
      overlapped with those for attention-deficit hyperactivity disorder (ADHD).
      Comprehensive assessment of the probands included separate Washington University
      in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U
      KSADS) interviews of parents about their children and of children about
      themselves. Hypersexuality and uninhibited people-seeking were assessed from the
      corresponding WASH-U-KSADS items. Microsatellite genotyping of the AVPR1A repeats
      was conducted using fluorescently labeled primers and detected by laser-induced
      fluorescence. Alleles were determined with the assistance of semi-automated
      allele-calling software. There were 32 complete, biological trios (28 informative
      families) for the GATA repeat and 34 complete, biological trios (30 informative
      families) for the complex repeat. Data were analyzed using case-control and
      family-based association methods. RESULTS: Preferential transmission of AVPR1A
      GATA or complex repeats was not significant for hypersexuality or uninhibited
      people-seeking, using the transmission disequilibrium test. Similarly, case
      control analyses found no significant associations between hypersexuality or
      uninhibited people-seeking and the number of AVPR1A GATA or complex repeats. For
      p < 0.05, there was about 80% power to detect odds ratios of 5.0 and 4.0 (in the
      family-based analyses) and 3.5 and 2.6 (in the case-control analyses), for allele
      frequencies of 0.1 and 0.5, respectively. CONCLUSION: Preferential transmission
      of AVPR1A to hypersexual or uninhibited people-seeking probands was not
      supported.

PMID- 16403187
TI  - Family environment in families with versus families without parental bipolar
      disorder: a preliminary comparison study.
AB  - OBJECTIVES: To compare family environmental characteristics of families with at
      least one bipolar parent and families with parents without any Axis I disorder.
      METHODS: Family environment of 24 families with at least one parent with bipolar
      disorder (BPD) and 27 families with healthy parents (healthy families, HF) were
      assessed using the Family Environment Scale (FES). We compared FES subscale
      scores between BPD and HF. We also compared FES normative scores with scores of
      BPD families. RESULTS: Seventeen (71%) of the 24 BPD families had at least one
      child with a mood disorder and one (3.7%) of the 27 HF had a child with a mood
      disorder. Families with BPD reported lower cohesion (p = 0.009) and
      expressiveness (p = 0.03) scores compared with HF, after controlling for group
      socioeconomic status differences. Bilineal BPD families had higher cohesion
      scores than unilineal BPD families (p = 0.05). We found no significant
      differences in any subscales between BPD families with (n = 9) versus without (n
      = 15) children with BPD. Compared with normative FES data BPD families reported
      lower cohesion (C) (p = 0.02) and independence (IND) (p = 0.004) scores and
      higher conflict (CON) (p = 0.02), intellectual-cultural orientation (ICO) (p =
      0.05), moral-religious emphasis (MRE) (p < 0.001) and control (CTL) (p < 0.001)
      scores. CONCLUSION: Our results suggest that members of BPD families may have
      difficulty communicating effectively with one another, suggesting that
      interventions aimed at improving this may be beneficial to patients with BPD.
      Results suggest that the impact of different lifestyles in different communities
      may influence FES scores, and thus it is important to use demographically matched
      comparison groups.

PMID- 16403188
TI  - Early symptoms of mania and the role of parental risk.
AB  - OBJECTIVES: The objectives of this study were to: (i) describe the phenomenology
      of youths diagnosed with subsyndromal bipolar disorders; (ii) describe the
      phenomenology of youngsters who are the children of bipolar parents, who are also
      experiencing subsyndromal symptoms of bipolar disorder (patients with
      'cyclotaxia'); and (iii) explore which symptoms may be most useful in identifying
      youths with cyclotaxia. METHODS: Four hundred outpatients between the ages of 5
      and 17 years received a diagnostic assessment and psychometric questionnaires
      pertaining to mood symptomatology and psychosocial functioning. Parental
      diagnostic information was also obtained. Children and adolescents were assigned
      to one of three diagnostic groups: a 'syndromal bipolar disorder (BP)' group (n =
      118), a 'sub-syndromal bipolar (SUB-BP)' group (n = 75), or a 'non-bipolar (NON
      BP)' group (n = 207). In addition, based on parental diagnoses, youths were
      assigned to either a high genetic risk group (n = 167) or a low genetic risk
      group (n = 233). RESULTS: Youths with subsyndromal bipolar disorders were found
      to have intermediate degrees of manic symptoms than youths with bipolar disorder
      and youths without a bipolar diagnosis. Offspring of parents having a bipolar
      disorder were more likely to show symptoms of hypomania and mania than youths
      without a bipolar parent. Youths at genetic risk for developing a bipolar
      disorder were not found to be at higher risk for having a diagnosis of attention
      deficit hyperactivity disorder or a disruptive behavior disorder. Finally,
      results suggest that elevated mood with irritability and rapid mood fluctuations
      are the key distinguishing characteristics of 'cyclotaxia'. CONCLUSIONS: There
      exists a group of youngsters who are the offspring of a parent/parents with a
      bipolar disorder who do not suffer from BP 1 or BP 2, yet have elevated mood
      symptoms and psychosocial dysfunction. As a result of these observations,
      treatment studies are needed for youths with 'cyclotaxia'.

PMID- 16403189
TI  - Are ethics committees always ethical?

PMID- 16403190
TI  - Nursing in a technological environment: nursing care in the operating room.
AB  - Operating room nurses continue to draw criticism regarding the appropriateness of
      a nursing presence in the operating room. The technological focus of the theatre
      and the ways in which nurses in the theatre have shaped and reshaped their
      practice in response to technological change have caused people within and
      outside the nursing profession to question whether operating room nursing is a
      technological rather than nursing undertaking. This paper reports findings from
      an ethnographic study that was conducted in an Australian operating department.
      The study examined the contribution of nurses to the work of the operating room
      through intensive observation and ethnographic interviews. This paper uses
      selected findings from the study to explore the ways in which nurses in theatre
      interpret their role in terms of caring in a technological environment.

PMID- 16403191
TI  - Adopting a constructivist approach to grounded theory: implications for research
      design.
AB  - Grounded theory is a popular research methodology that is evolving to account for
      a range of ontological and epistemological underpinnings. Constructivist grounded
      theory has its foundations in relativism and an appreciation of the multiple
      truths and realities of subjectivism. Undertaking a constructivist enquiry
      requires the adoption of a position of mutuality between researcher and
      participant in the research process, which necessitates a rethinking of the
      grounded theorist's traditional role of objective observer. Key issues for
      constructivist grounded theorists to consider in designing their research studies
      are discussed in relation to developing a partnership with participants that
      enables a mutual construction of meaning during interviews and a meaningful
      reconstruction of their stories into a grounded theory model.

PMID- 16403192
TI  - Multidimensional structures of comprehensive accessibility of community support
      for people with mental disorders in Japan: a nationwide investigation.
AB  - The purpose of this study was to define the concept of comprehensive
      accessibility of community support for people with mental disorders and to
      clarify the multidimensional structures of comprehensive accessibility. We
      developed a self-administered questionnaire consisting of 47 items. A complete
      list of the municipalities in Japan was prepared, and the questionnaire was
      mailed to 3310 municipalities. Principal component analyses were applied to valid
      data in order to analyse the index and multidimensional structures of
      comprehensive accessibility. As a result, 14 principal components of community
      support for people with mental disorders were extracted. These principal
      components were interpreted as the scales for the evaluation of comprehensive
      accessibility. The two first principal component scores were interpreted as the
      index indicating the level of comprehensive accessibility. The other 12 principal
      components were interpreted as the scales constituting the multidimensional space
      of comprehensive accessibility.

PMID- 16403193
TI  - A cross-sectional survey of calcium intake in relation to knowledge of
      osteoporosis and beliefs in young adult women.
AB  - This investigation found that young adult women (n = 265) were very likely
      (80.6%) to have accurate knowledge about osteoporosis but also typically had a
      low calcium intake (454 mg/day). The women in this study believed that they were
      at risk of osteoporosis but felt that prevention was difficult. Meanwhile, they
      held the opinion that osteoporosis is not serious and that taking preventative
      measures would not be worthwhile. The factors that most strongly affected the
      intake of calcium by women were, in order, knowledge, number of children, self
      rated health score, Body Mass Index, graduation from high school, experience of
      bone density examination and family history. These seven items accounted for
      31.8% of the variation in calcium intake.

PMID- 16403194
TI  - The relationship between exercise, Body Mass Index and menopausal symptoms in
      midlife Australian women.
AB  - The main objective of the study was to examine the relationship between physical
      activity and Body Mass Index (BMI) on menopausal symptoms in Australian midlife
      women. This study is a secondary data analysis of the Queensland Midlife Women
      Health Study (2001), which included a randomized, population-based postal survey
      with a questionnaire. Selected women completed a questionnaire, which included
      measurement of sociodemographic factors (age, employment and education
      attainment), general health, use of hormone replacement therapy, smoking,
      exercise pattern and BMI. The measures that are reported in this paper include
      menopausal symptoms, BMI and exercise. After adjusting for confounding variables,
      significant multivariate difference was still found for most menopausal symptoms,
      including a significant relationship between somatic symptoms, psychological
      symptoms, depression and anxiety. No significant relationship was seen, however,
      between vasomotor symptoms, sexual function and exercise. In conclusion, the
      study showed that exercise was effective in relieving somatic and psychological
      symptoms, including depression and anxiety. These findings are promising news for
      women who are interested in using non-pharmacological interventions for relieving
      menopausal symptoms.

PMID- 16403195
TI  - Putting the evidence into practice: the King Faisal Specialist Hospital and
      Research Centre experience.
AB  - For more than a decade, evidence-based practice has become the desired aim behind
      organized health care. Although a plethora of reasons exist as to why clinicians
      are reluctant to adopt research-based findings, the fundamentals relate to
      management of change and the nature of the individuals involved. Large
      organizations, with their daily routines and operations, are inherently difficult
      to change. Hence, one has to use the very structures that drive the organization
      to effect 'sustained' change. In large tertiary care facilities, such as the King
      Faisal Specialist Hospital and Research Centre, these structures are policies and
      procedures. This paper provides details of the process developed by the Nursing
      Affairs Practice Committee of the King Faisal Specialist Hospital and Research
      Centre to achieve the committee mandate of: 'Establish and implement an evidence
      based process for the systematic review and revision of nursing clinical
      standards, policies, procedures and protocols'.

PMID- 16403196
TI  - 'They first killed his heart (then) he took his own life'. Part 2: Practice
      implications.
AB  - This paper is the second in a two-part series dedicated to mental health needs of
      refugees and asylum seekers. Against a background of selective review of
      literature and context in paper 1, this paper describes practical steps in
      meeting the mental health needs of refugees and asylum seekers. Nurses see
      refugees and asylum seekers at the very point of their distress--often outside of
      or external to immigration detention facilities. Practical strategies are
      presented for the generation of trust and supportive counselling with
      implications drawn for nurses working across a range of practice settings, such
      as in accident and emergency departments, psychiatric clinics, community-health
      centres and as general practice nurses. Continuity and integration of mental
      health care is achieved by bridging discrete elements in the asylum seeker
      journey through legal reviews, news from home and ongoing psychosocial stressors,
      in the context of different episodes, interventions by different providers or
      changes in illness status. Also important will be actions that build resilience
      intrinsically over time, such as the asylum seeker's values, sustained supportive
      interpersonal relationships and therapeutic care plans.

PMID- 16403197
TI  - Verbal short-term memory in individuals with congenital articulatory disorders:
      new empirical data and review of the literature.
AB  - BACKGROUND: To investigate the nature of the articulatory rehearsal mechanism of
      the Articulatory Loop in Baddeley's Working Memory model, it seems particularly
      important to study individuals who developed a deficit (dysarthria) or total
      abolition (anarthria) of the ability to articulate language following a cerebral
      lesion. METHOD: In this study, a forced-choice recognition procedure for word
      sequences of increasing length was used to evaluate verbal short-term memory in
      nine individuals with severe congenital motor and verbal disabilities (seven
      anarthric and two severely dysarthric) and associated intellectual disability
      (ID) and 30 normal children of comparable mental age. RESULTS: The normal
      children exhibited classical phonological similarity effects (better performance
      on acoustically dissimilar than on similar word lists), word length (greater
      accuracy on two-syllable than on four-syllable word lists) and frequency of
      occurrence (an advantage of high-frequency over low-frequency words). Instead,
      all of these effects were lacking in the experimental group. CONCLUSIONS: These
      data suggest that persons with congenital anarthria/dysarthria and ID present
      defective maturation at many levels of the Articulatory Loop and reduced
      contribution of semantic-lexical processing in the temporary retention of
      phonological sequences. It is likely that in these individuals both communicative
      deficits and ID play a role in the impaired development of verbal short-term
      memory abilities.

PMID- 16403198
TI  - Repetitive and ritualistic behaviour in children with Prader-Willi syndrome and
      children with autism.
AB  - BACKGROUND: Recent research has shown that the range of repetitive behaviour seen
      in individuals with Prader-Willi syndrome (PWS) extends beyond food-related
      behaviour. METHODS: The presence and intensity of repetitive, rigid and
      routinized behaviour in children with PWS was compared with that seen in children
      with another neurodevelopmental condition in which repetitive behaviour is
      common: children with autism. Parents completed the Childhood Routines Inventory
      (CRI). RESULTS: Contrary to our predictions, controlling for developmental level,
      children with PWS and children with autism showed similar levels of repetitive
      and ritualistic behaviour overall and on the two CRI factors measuring 'just
      right' and 'repetitive' behaviour. Indeed, the majority of the sample of parents
      of children with PWS endorsed most items on the CRI. However there was some
      specificity at the level of individual items with parents of children with PWS
      more frequently endorsing an item on 'collecting and storing objects' and parents
      of children with autism more frequently endorsing 'lining up objects', 'has a
      strong preference for certain foods' and 'seems aware of detail at home'.
      CONCLUSIONS: These findings confirm the range of repetitive behaviours that form
      part of the behavioural phenotype of PWS, including insistence on sameness and
      'just right' behaviours, and uncover a surprising overlap with those seen in
      children with autism. Clinical management for children with PWS should include
      advice and education regarding management of repetitive and rigid behaviour.
      Future research should investigate whether the repetitive behaviours that form
      part of the behavioural phenotype of both PWS and autism are associated with a
      common neuropsychological, neurotransmitter or genetic origin.

PMID- 16403199
TI  - A language programme to increase the verbal production of a child dually
      diagnosed with Down syndrome and autism.
AB  - BACKGROUND: The incidence of children dually diagnosed with Down syndrome and
      autism is estimated to be as high as 11%. There is a paucity of research
      investigating linguistic treatment interventions for such children. This single
      subject experiment examined a programme designed to increase the language
      production and verbal behaviour of a 9-year-old dually diagnosed boy who had been
      receiving a 15-h/week home-based applied behaviour analysis (ABA) programme.
      METHODS: Training principles were derived from previously empirically validated
      research in discrete trail learning and natural environment teaching, as well as
      modified incidental teaching procedures. The crux of the language programme
      involved withholding reinforcement until a spoken request was made. RESULTS:
      Language production noticeably increased for each target area after the
      introduction of the language programme and was maintained at a 9-month follow-up
      session. CONCLUSIONS: A combined treatment approach incorporating direct
      instruction, natural environment teaching and incidental teaching can be
      effective in increasing and maintaining responsive and spontaneous speech in a
      child with Down syndrome diagnosed with autism. Replication studies are needed
      with such multiple dually diagnosed children to further evaluate the
      effectiveness and generalizability of this combined language programme.

PMID- 16403200
TI  - A Bayesian belief network for quality assessment: application to employment
      officer support.
AB  - BACKGROUND: 'Supported' employment stipulates that disabled people should have
      real jobs for real pay. This paper models kinds of supported employment, assesses
      how the support and placement features affect its outcomes and its quality from
      the perspective of the employees, and provides a dynamic model to help explore
      what types of interventions might promote greater social inclusion for people
      with learning and other disabilities. METHOD: Bayesian belief networks (BBNs)
      provide the general framework for modelling the relationships between the
      variables and features of interest. The structure, probabilistic specification
      and quality indicators were elicited from project advisory groups, including
      people with learning disability, and took into account a pilot survey of 30
      individuals. A subsequent survey of 1,461 supported employees was used to update
      the model and to provide actual assessments of quality of placement. RESULTS: We
      present the BBN methodology in some detail, as novel to this discipline. We show
      how the model was constructed, and its implications for supported employment. We
      derive indices for quality of placement, taking into account the views of
      clients. We show how survey and individual results can be used to update the
      model. Use of the model suggests that quality of placement is, on average,
      relatively high, with small differences between groups with differing primary
      disability. CONCLUSIONS: The BBN is the appropriate methodology to model complex
      relationships and interventions for problems such as these. The model developed
      in this study can be used to assess and improve the fit between people and jobs,
      both at the individual level and for groups of employees, and can take into
      account different kinds of quality for different stakeholders.

PMID- 16403201
TI  - What am I doing in Timbuktu: person-environment picture recognition for persons
      with intellectual disability.
AB  - BACKGROUND: The aim of this study was to examine the effects of familiarity of
      depicted persons and environments in recognition of photographs for pupils with
      different degrees of intellectual disability (ID). METHOD: Forty-five pupils with
      ID participated. RESULTS: An interaction effect between the two variables, person
      and environment, was found in addition to main effects for both the variables.
      Pictures of the test person himself or herself in familiar environments were
      easier to recognize than in unfamiliar environments, whereas the opposite was
      found for pictures of other familiar persons. No interaction effects of degree of
      ID were found. CONCLUSIONS: The interaction pattern is explained in terms of
      absent, present or implausible semantic associations between the person and the
      environmental context. The results are discussed in relation to augmentative and
      alternative communication with photographs.

PMID- 16403202
TI  - Verbal communication outcomes in children with autism after in-home father
      training.
AB  - BACKGROUND: This retrospective study examined the efficacy of in-home father
      training on the communicative outcomes of children with autism. The in-home
      training consisted of two components: (1) expectant waiting; and (2) imitation
      with animation. METHODS: Efficacy of parent training was examined by measuring
      the ratio of utterances produced by the parents to the utterances produced by the
      children and the number of verbal imitation by the parents. Outcomes of the
      children's verbal production were examined by measuring the number of (1) single
      word utterances; (2) different words produced; and (3) verbal response to
      questions. RESULTS: Following training there was a decrease in the ratio of
      parent to child utterances and an increase in (1) the use of imitation by the
      parents; and (2) the number of single words and different words produced by the
      children. DISCUSSION: Results of this study suggested that the parents had
      learned to wait for their children to communicate verbally during communicative
      interactions and to interact more efficiently with their children by using verbal
      imitation. Overall, the results of this study support the efficacy of parent
      training that focuses on promotion of social reciprocity, and have important
      implications for clinicians and future research.

PMID- 16403203
TI  - Outcome in adult life for people with Williams syndrome-- results from a survey
      of 239 families.
AB  - BACKGROUND: Although there has been considerable research into the genotype and
      phenotype of Williams syndrome, there have been relatively few studies of long
      term prognosis. As a preliminary to a more detailed investigation of adults with
      Williams syndrome, a parental questionnaire was distributed to members of the UK
      Williams Syndrome Foundation, focusing on areas of skill and difficulties in
      adult life. METHOD: A postal questionnaire was distributed to all members of the
      UK Williams Syndrome Foundation who had a son or daughter aged 18 years or over.
      The questionnaire covered issues related to the physical and mental health of the
      adults with Williams syndrome, together with questions about educational and
      employment status, self-help and independence skills. RESULTS: Out of a total of
      290 questionnaires distributed, 239 were returned (82% response rate). The data
      highlighted the continuing high rates of physical problems in this group and
      apparent increases in rates of mental health problems with age. Parents also
      expressed their concerns about the lack of adequate support and care. Educational
      and employment attainments were generally low and self-help skills were
      relatively poor. DISCUSSION: The findings highlight the need for far better
      understanding of conditions such as Williams syndrome among professionals working
      in adult services and the need for more adequate support from educational, health
      and social services.

PMID- 16403206
TI  - Ergonomics for healthcare providers.

PMID- 16403205
TI  - 2004 AANP National Nurse Practitioner Sample Survey, part III: NP income and
      benefits.

PMID- 16403207
TI  - The nurse practitioner as leader.

PMID- 16403208
TI  - Assessment and monitoring of glycemic control in primary diabetes care:
      monitoring techniques, record keeping, meter downloads, tests of average
      glycemia, and point-of-care evaluation.
AB  - PURPOSE: To present a review of glucose monitoring methods useful in primary
      care. DATA SOURCES: Pertinent publications in the literature, printed materials
      and resources, and the clinical experience of the authors as a referral center
      for care of patients with diabetes. CONCLUSIONS: Regular monitoring of glucose
      control is an integral and important aspect of diabetes care. It allows the
      advanced practice nurse (APN) to assess whether diabetes goals are being met or
      not, involves patients in the care of their disease, and assists in making
      informed treatment decisions. IMPLICATIONS FOR PRACTICE: A working knowledge of
      glucose monitoring methods, monitors, testing devices, and laboratory tests is
      extremely beneficial for the APN in attaining standards of care for patients with
      diabetes.

PMID- 16403209
TI  - Diabetes nurse case management: an effective tool.
AB  - PURPOSE: In March 2000, a large tertiary military medical treatment facility on
      the east coast implemented a diabetes nurse case management program to coordinate
      care for patients with diabetes mellitus type 1 or type 2 and a hemoglobin A1c
      value of 8.0% or greater. Although proven successful for patients while enrolled
      in the program, there was a lack of research that evaluated how successful
      patients were at continuing diabetes self-management once discharged. This study
      evaluated glycosylated hemoglobin A1c (A1c), total cholesterol (TC),
      triglyceride, and low-density lipoprotein (LDL) levels in patients at admission,
      discharge, and 6 months following discharge from the program. DATA SOURCES: A
      retrospective medical record review of laboratory data was evaluated using
      descriptive statistics and paired t-test. CONCLUSIONS: Significant reductions in
      A1c and TC values from admission to discharge were achieved, which the patients
      maintained 6 months following discharge. There was also a significant reduction
      in LDL value from admission to 6 months following discharge. IMPLICATIONS FOR
      PRACTICE: This study supports the value of nurse case management for patients
      with diabetes.

PMID- 16403210
TI  - Effective interventions for lifestyle change after myocardial infarction or
      coronary artery revascularization.
AB  - PURPOSE: This science clinical paper reviews medical literature and examines
      interventions that are currently used to assist patients in achieving lifestyle
      change after myocardial infarction or coronary artery revascularization.
      Interventions that focused on both provider- and patient-implemented strategies
      were included. The effectiveness of these interventions to significantly reduce
      coronary heart disease risk factors was explored. DATA SOURCES: Original
      longitudinal research studies or reviews indexed in PubMed between 1999 and 2004
      were included. Eight studies were identified that met the inclusion criteria and
      presented successful interventions to increase participants' adherence to
      recommended lifestyle changes. CONCLUSIONS: Current strategies for achieving
      recommended risk factor reductions include frequent follow-up, intensive diet
      changes, individualized and group exercise, coaching, group meetings, education
      on lifestyle modification and behavior change, and formal cardiac rehabilitation
      programs. IMPLICATIONS FOR PRACTICE: Nurse Practitioners can help close the gap
      between evidence-based recommendations and clinical practice by implementing
      education programs in their practices and in the community. Recommendations
      include frequent follow-up visits, negotiating personalized treatment plans, and
      a general emphasis on therapeutic lifestyle change as an essential component of
      the treatment plan.

PMID- 16403211
TI  - SuperMimic--fitting peptide mimetics into protein structures.
AB  - BACKGROUND: Various experimental techniques yield peptides that are biologically
      active but have unfavourable pharmacological properties. The design of
      structurally similar organic compounds, i.e. peptide mimetics, is a challenging
      field in medicinal chemistry. RESULTS: SuperMimic identifies compounds that mimic
      parts of a protein, or positions in proteins that are suitable for inserting
      mimetics. The application provides libraries that contain peptidomimetic building
      blocks on the one hand and protein structures on the other. The search for
      promising peptidomimetic linkers for a given peptide is based on the
      superposition of the peptide with several conformers of the mimetic. New
      synthetic elements or proteins can be imported and used for searching.
      CONCLUSION: We present a graphical user interface for finding peptide mimetics
      that can be inserted into a protein or for fitting small molecules into a
      protein. Using SuperMimic, promising locations in proteins for the insertion of
      mimetics can be found quickly and conveniently.

PMID- 16403213
TI  - Two Surgeon General's reports on smoking and cancer: a historical investigation
      of the practice of causal inference.
AB  - BACKGROUND: The epidemiologic literature is replete with conceptual discussions
      about causal inference, but little is known about how the causal criteria are
      applied in public health practice. The criteria for causal inference in use today
      by epidemiologists have been shaped substantially by their use over time in
      reports of the U.S. Surgeon General on Smoking and Health. METHODS: We reviewed
      two classic reports on smoking and health from expert committees convened by the
      US Surgeon General, in 1964 and 1982, in order to evaluate and contrast how the
      committees applied causal criteria to the available evidence for the different
      cancer sites at different time periods. We focus on the evidence for four cancer
      sites in particular that received detailed reviews in the reports: lung, larynx,
      esophagus and bladder. RESULTS: We found that strength of association and
      coherence (especially dose-response, biological plausibility and epidemiologic
      sense) appeared to carry the most weight; consistency carried less weight, and
      temporality and specificity were apparently not applied at all in some cases. No
      causal claim was made for associations with a summary odds ratio of less than
      3.0. CONCLUSION: Our findings suggest that the causal criteria as described in
      textbooks and the Surgeon General reports can have variable interpretations and
      applications in practice. While the authors of these reports may have considered
      evidential factors that they did not explicitly cite, such lack of transparency
      of methods undermines the purpose of the causal criteria to promote objective,
      evidence-based decision making. Further empirical study and critical examination
      of the process by which causal conclusions are reached can play an important role
      in advancing the practice of epidemiology by helping public health scientists to
      better understand the practice of causal inference.

PMID- 16403212
TI  - Crystal structure of a DNA polymerase sliding clamp from a Gram-positive
      bacterium.
AB  - BACKGROUND: Sliding DNA clamps are processivity factors that are required for
      efficient DNA replication. DNA polymerases maintain proximity to nucleic acid
      templates by interacting with sliding clamps that encircle DNA and thereby link
      the polymerase enzyme to the DNA substrate. Although the structures of sliding
      clamps from Gram-negative bacteria (E. coli), eukaryotes, archaea, and T4-like
      bacteriophages are well-known, the structure of a sliding clamp from Gram
      positive bacteria has not been reported previously. RESULTS: We have determined
      the crystal structure of the dimeric beta subunit of the DNA polymerase III
      holoenzyme of Streptococcus pyogenes. The sliding clamp from this Gram-positive
      organism forms a ring-shaped dimeric assembly that is similar in overall
      structure to that of the sliding clamps from Gram-negative bacteria,
      bacteriophage T4, eukaryotes and archaea. The dimer has overall dimensions of
      approximately 90 A x approximately 70 A x approximately 25 A with a central
      chamber that is large enough to accommodate duplex DNA. In comparison to the
      circular shape of other assemblies, the S. pyogenes clamp adopts a more
      elliptical structure. CONCLUSION: The sequences of sliding clamps from S.
      pyogenes and E. coli are only 23% identical, making the generation of structural
      models for the S. pyogenes clamp difficult in the absence of direct experimental
      information. Our structure of the S. pyogenes beta subunit completes the catalog
      of clamp structures from all the major sequence grouping of sliding clamps. The
      more elliptical rather than circular structure of the S. pyogenes clamp implies
      that the topological nature of encircling DNA, rather than a precise geometric
      shape, is the most conserved aspect for this family of proteins.

PMID- 16403214
TI  - Effect of a brief intervention on evidence-based medicine skills of pediatric
      residents.
AB  - BACKGROUND: While Evidence-Based Medicine (EBM) skills are increasingly being
      taught in medical schools, teaching quality has been insufficient, so that
      incoming pediatric residents lack adequate EBM skills required for patient care.
      The objective of this study was to evaluate the effectiveness of a brief teaching
      module developed to improve EBM skills of pediatric residents. METHODS: With-in
      subjects study design with pre- and post-test evaluation was performed in a large
      urban pediatric residency training program in Brooklyn, New York. We included PGY
      1s during intern orientation, while second and third year pediatric residents
      were selected based on schedule availability. Sixty-nine residents were enrolled
      into the study, 60 (87%) completed the training. An EBM training module
      consisting of three or four weekly two-hour seminars was conducted. The module
      was designed to teach core EBM skills including (1) formulating answerable
      clinical questions, (2) searching the evidence, (3) critical appraisal skills
      including validity and applicability, and (4) understanding levels of evidence
      and quantitative results for therapy articles. A portion of the Fresno test of
      competence in EBM was used to assess EBM skills. The test presented a clinical
      scenario that was followed by nine short answer questions. One to three questions
      were used to assess EBM skills for each of the four core skills. The kappa co
      efficient for inter-rater reliability was 0.74 (95% CI: 0.56-0.92). RESULTS:
      Prior to the training module, the residents achieved a mean score of 17% correct
      overall. Post intervention, the mean score increased to 63% with improvement in
      each EBM category. A mean of 4.08 more questions (out of 9) were answered
      correctly after the training (95% CI of 3.44-4.72). CONCLUSION: A brief training
      module was effective in improving EBM skills of pediatric residents.

PMID- 16403215
TI  - Determinants of adult vaccination at inner-city health centers: a descriptive
      study.
AB  - BACKGROUND: Pneumococcal polysaccharide vaccination rates among adults 65 years
      and older or less than 65 years with high risk medical conditions are still below
      Healthy People 2010 recommended levels of 90%. This study was designed to: 1)
      assess self-reported pneumococcal vaccination rates following health center level
      interventions to increase adult vaccination rates; and 2) determine factors
      associated with vaccination. METHODS: Tailored interventions to increase
      immunizations were implemented at two inner-city health centers. We surveyed 375
      patients 50 years of age and older. Multivariate logistic regression examines the
      predictors of 1) self-reported pneumococcal vaccination and 2) combined self
      reported influenza and pneumococcal vaccination. Both of these models were
      stratified by age group (50-64 years and 65 years and older). RESULTS:
      Pneumococcal vaccination rates were 45% by self-report, 55% by medical record
      review, 69% for patients 65 years old and older, 32% for patients 50-64 years;
      they did not differ by race. Receipt of the previous season's influenza vaccine
      was significantly related to pneumococcal vaccination among both younger and
      older patients. Receiving both the pneumococcal vaccine and the most recent
      influenza vaccine compared with receiving neither, among younger patients was
      related to unemployment, more frequent physician visits, and belief that those
      who do not receive the flu shot are more susceptible to the flu. For older
      patients, receipt of both vaccines was related to nonsmoking status, believing
      that friends/family think the patient should be vaccinated, seeing posters
      advertising flu shot clinics, and belief that those who do not receive the flu
      shot are more susceptible to the flu. CONCLUSION: Our findings suggest that
      improving overall pneumococcal vaccination rates among eligible adults, has the
      potential to eliminate racial disparities. Interventions delivering vaccination
      messages specific to older and younger adult groups may be the best strategy for
      improving adult vaccination rates.

PMID- 16403216
TI  - Common angiotensin receptor blockers may directly modulate the immune system via
      VDR, PPAR and CCR2b.
AB  - BACKGROUND: There have been indications that common Angiotensin Receptor Blockers
      (ARBs) may be exerting anti-inflammatory actions by directly modulating the
      immune system. We decided to use molecular modelling to rapidly assess which of
      the potential targets might justify the expense of detailed laboratory
      validation. We first studied the VDR nuclear receptor, which is activated by the
      secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the
      expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing
      hormone) and the Parathyroid Hormone (PTH). Additionally we examined Peroxisome
      Proliferator-Activated Receptor Gamma (PPARgamma), which affects the function of
      phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b), which recruits
      monocytes to the site of inflammatory immune challenge. RESULTS: Telmisartan was
      predicted to strongly antagonize (Ki asymptotically equal to 0.04 nmol) the VDR.
      The ARBs Olmesartan, Irbesartan and Valsartan (Ki asymptotically equal to10 nmol)
      are likely to be useful VDR antagonists at typical in-vivo concentrations.
      Candesartan (Ki asymptotically equal to 30 nmol) and Losartan (Ki asymptotically
      equal to 70 nmol) may also usefully inhibit the VDR. Telmisartan is a strong
      modulator of PPARgamma (Ki asymptotically equal to 0.3 nmol), while Losartan (Ki
      asymptotically equal to 3 nmol), Irbesartan (Ki asymptotically equal to 6 nmol),
      Olmesartan and Valsartan (Ki asymptotically equal to 12 nmol) also seem likely to
      have significant PPAR modulatory activity. Olmesartan and Irbesartan (Ki
      asymptotically equal to 9 nmol) additionally act as antagonists of a theoretical
      model of CCR2b. Initial validation of this CCR2b model was performed, and a
      proposed model for the Angiotensin II Type1 receptor (AT2R1) has been presented.
      CONCLUSION: Molecular modeling has proven valuable to generate testable
      hypotheses concerning receptor/ligand binding and is an important tool in drug
      design. ARBs were designed to act as antagonists for AT2R1, and it was not
      surprising to discover their affinity for the structurally similar CCR2b.
      However, this study also found evidence that ARBs modulate the activation of two
      key nuclear receptors-VDR and PPARgamma. If our simulations are confirmed by
      experiment, it is possible that ARBs may become useful as potent anti
      inflammatory agents, in addition to their current indication as cardiovascular
      drugs.

PMID- 16403218
TI  - Variation in hepatitis C services may lead to inequity of heath-care provision: a
      survey of the organisation and delivery of services in the United Kingdom.
AB  - BACKGROUND: Chronic hepatitis C infection (CHC) is a major healthcare problem.
      Effective anti-viral therapy is available. To maximise population effectiveness,
      co-ordinated services for detection and management of patients with CHC are
      required. There is a need to determine patterns of healthcare delivery to plan
      improvements. A study was conducted to determine workload, configuration and care
      processes of current UK services available to manage patients with CHC. METHODS:
      A cross-sectional questionnaire survey of consultant members of British
      Association for the Study of the Liver (n = 53), Infectious Disease consultants
      (n = 43), and a 1 in 5 sample of Genito-Urinary Medicine (n = 48) and
      gastroenterologists (n = 200). RESULTS: Response rate was 70%. 40% of respondents
      provided a comprehensive service (included treatment and follow-up): speciality
      of clinical leads identified as Hepatology (37%); Gastroenterology (47%); and
      Infectious Disease (16%). The estimated number of patients managed by respondents
      was about 23,000 with an upward trend over the previous 3 years. There was
      variation between comprehensive service providers, including unit size,
      eligibility criteria for treatment, and drug regimes. Key barriers to quality of
      care identified were staffing capacity, funding of treatment and patient non
      attendance. Most English strategic health authorities had at least one
      comprehensive service provider. CONCLUSION: There was significant variation in
      all aspects of the patient pathway which may contribute to inequity of health
      care provision. Services need to be expanded to form geographical clinical
      networks, and properly resourced to ensure greater uptake and more equitable
      delivery of services if the future burden of chronic liver disease is to be
      reduced.

PMID- 16403217
TI  - Influence of methylphenidate on brain development--an update of recent animal
      experiments.
AB  - Methylphenidate (MPH) is the most commonly used drug to treat attention
      deficit/hyperactivity disorder (ADHD) in children effectively and safely. In
      spite of its widespread application throughout one of the most plastic and
      sensitive phases of brain development, very little is known to date about its
      long-term effects on brain structure and function. Hence, this short review
      updates the influence of MPH on brain development, since recent human and animal
      studies suggest that MPH alters the dopaminergic system with long-term effects
      beyond the termination of treatment.Animal studies imply that the effects of MPH
      may depend on the neural responder system: Whereas structural and functional
      parameters are improved by MPH in animals with psychomotor impairments, they
      remain unaltered or get worse in healthy controls. While recent behavioural
      studies do not fully support such a differential effect of MPH in ADHD, the
      animal studies certainly prompt for further investigation of this issue.
      Furthermore, the abuse of MPH, when (rarely) intravenously applied, may even
      impair the maturation of dopaminergic fibres in subcortical brain areas. This
      argues for careful clinical assessment and diagnostics of ADHD symptomatology not
      only in conjunction with the prescription of MPH. Hence, one should be assured
      that MPH is only given to children with clear ADHD symptomatology leading to
      psychosocial impairment. The animal data suggest that under these conditions MPH
      is supportive for brain development and the related behaviour in children with
      ADHD.

PMID- 16403220
TI  - Sexually transmitted infections in Saudi Arabia.
AB  - BACKGROUND: Data on sexually transmitted infections (STIs) in Saudi Arabia (SA)
      and other Islamic countries are limited. This study describes the results of a
      five-year surveillance for STIs in SA. METHODS: This is a case series descriptive
      study of all confirmed STIs diagnosed in SA from January, 1995 through December,
      1999. RESULTS: A total of 39049 STIs were reported to the Ministry of Health.
      Reported STIs included nongonococcal urethritis (14557 infections, 37.3%),
      trichomoniasis (10967 infections, 28.1%), gonococcal urethritis (5547 infections,
      14.2%), syphilis (3385 infections, 8.7%), human immunodeficiency virus (2917
      infections, 7.5%), genital warts (1382, 3.5%), genital herpes (216 infections,
      0.6%), and chancroid (78 infections, 0.2%). The average annual incidence of STIs
      per 100,000 population for Saudis and non-Saudis, respectively, was as follows:
      14.8 and 7.5 for nongonococcal urethritis, 9.4 and 10.4 for trichomoniasis, 5.2
      and 4.2 for gonorrhea, 1.7 and 6.4 for syphilis, 0.6 and 8.0 for HIV, 1.4 and 0.7
      for genital warts, 0.1 and 0.4 for genital herpes, and 0.1 and 0.1 for chancroid.
      The incidence of STIs was somewhat steady over the surveillance period except for
      nongonococcal urethritis which gradually increased. CONCLUSION: Nongonococcal
      urethritis, trichomoniasis, and gonococcal urethritis were the most commonly
      reported STIs in SA. Even though the incidence of STIs in SA is limited,
      appropriate preventive strategies that conform to the Islamic rules and values
      are essential and should be of highest priority for policymakers because of the
      potential of such infections to spread particularly among the youth.

PMID- 16403219
TI  - Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and
      dissociation from Bcl-XL.
AB  - BACKGROUND: Pim-1, 2 and 3 are a group of enzymes related to the calcium
      calmodulin family of protein kinases. Over-expression of Pim-1 and Pim-2 in mice
      promotes the development of lymphomas, and up-regulation of Pim expression has
      been observed in several human cancers. RESULTS: Here we show that the pim
      kinases are constitutively active when expressed in HEK-293 cells and are able to
      phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and
      Ser155 in vitro and in cells. In vitro mapping showed that Pim-2 predominantly
      phosphorylated Ser112, while Pim-1 phosphorylated Ser112, but also Ser136 and
      Ser155 at a reduced rate compared to Ser112. Pim-3 was found to be the least
      specific for Ser112, and the most effective at phosphorylating Ser136 and Ser155.
      Pim-3 was also able to phosphorylate other sites in Bad in vitro, including
      Ser170, another potential in vivo site. Mutation of Ser136 to alanine prevented
      the phosphorylation of Ser112 and Ser155 by Pim kinases in HEK-293 cells,
      suggesting that this site must be phosphorylated first in order to make the other
      sites accessible. Pim phosphorylation of Bad was also found to promote the 14-3-3
      binding of Bad and block its association with Bcl-XL. CONCLUSION: All three Pim
      kinase family members predominantly phosphorylate Bad on Ser112 and in addition
      are capable of phosphorylating Bad on multiple sites associated with the
      inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be
      consistent with the proposed function of Pim kinases in promoting cell
      proliferation and preventing cell death.

PMID- 16403221
TI  - A high level interface to SCOP and ASTRAL implemented in python.
AB  - BACKGROUND: Benchmarking algorithms in structural bioinformatics often involves
      the construction of datasets of proteins with given sequence and structural
      properties. The SCOP database is a manually curated structural classification
      which groups together proteins on the basis of structural similarity. The ASTRAL
      compendium provides non redundant subsets of SCOP domains on the basis of
      sequence similarity such that no two domains in a given subset share more than a
      defined degree of sequence similarity. Taken together these two resources provide
      a 'ground truth' for assessing structural bioinformatics algorithms. We present a
      small and easy to use API written in python to enable construction of datasets
      from these resources. RESULTS: We have designed a set of python modules to
      provide an abstraction of the SCOP and ASTRAL databases. The modules are designed
      to work as part of the Biopython distribution. Python users can now manipulate
      and use the SCOP hierarchy from within python programs, and use ASTRAL to return
      sequences of domains in SCOP, as well as clustered representations of SCOP from
      ASTRAL. CONCLUSION: The modules make the analysis and generation of datasets for
      use in structural genomics easier and more principled.

PMID- 16403222
TI  - Real-time PCR quantification of human complement C4A and C4B genes.
AB  - BACKGROUND: The fourth component of human complement (C4), an essential factor of
      the innate immunity, is represented as two isoforms (C4A and C4B) in the genome.
      Although these genes differ only in 5 nucleotides, the encoded C4A and C4B
      proteins are functionally different. Based on phenotypic determination,
      unbalanced production of C4A and C4B is associated with several diseases, such as
      systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases,
      moreover with higher morbidity and mortality of myocardial infarction and
      increased susceptibility for bacterial infections. Despite of this major clinical
      relevance, only low throughput, time and labor intensive methods have been used
      so far for the quantification of C4A and C4B genes. RESULTS: A novel quantitative
      real-time PCR (qPCR) technique was developed for rapid and accurate
      quantification of the C4A and C4B genes applying a duplex, TaqMan based
      methodology. The reliable, single-step analysis provides the determination of the
      copy number of the C4A and C4B genes applying a wide range of DNA template
      concentration (0.3-300 ng genomic DNA). The developed qPCR was applied to
      determine C4A and C4B gene dosages in a healthy Hungarian population (N = 118).
      The obtained data were compared to the results of an earlier study of the same
      population. Moreover a set of 33 samples were analyzed by two independent
      methods. No significant difference was observed between the gene dosages
      determined by the employed techniques demonstrating the reliability of the novel
      qPCR methodology. A Microsoft Excel worksheet and a DOS executable are also
      provided for simple and automated evaluation of the measured data. CONCLUSION:
      This report describes a novel real-time PCR method for single-step quantification
      of C4A and C4B genes. The developed technique could facilitate studies
      investigating disease association of different C4 isotypes.

PMID- 16403223
TI  - Public awareness of risk factors for cancer among the Japanese general
      population: a population-based survey.
AB  - BACKGROUND: The present study aimed to provide information on awareness of the
      attributable fraction of cancer causes among the Japanese general population.
      METHODS: A nationwide representative sample of 2,000 Japanese aged 20 or older
      was asked about their perception and level of concern about various environmental
      and genetic risk factors in relation to cancer prevention, as a part of an
      Omnibus Survey. Interviews were conducted with 1,355 subjects (609 men and 746
      women). RESULTS: Among 12 risk factor candidates, the attributable fraction of
      cancer-causing viral and bacterial infection was considered highest (51%),
      followed by that of tobacco smoking (43%), stress (39%), and endocrine-disrupting
      chemicals (37%). On the other hand, the attributable fractions of cancer by
      charred fish and meat (21%) and alcohol drinking (22%) were considered low
      compared with other risk factor candidates. For most risk factors, attributable
      fraction responses were higher in women than in men. As a whole, the subjects
      tended to respond with higher values than those estimated by epidemiologic
      evidence in the West. The attributable fraction of cancer speculated to be
      genetically determined was 32%, while 36% of cancer was considered preventable by
      improving lifestyle. CONCLUSION: Our results suggest that awareness of the
      attributable fraction of cancer causes in the Japanese general population tends
      to be dominated by cancer-causing infection, occupational exposure, air pollution
      and food additives rather than major lifestyle factors such as diet.

PMID- 16403224
TI  - BRAF mutations are associated with distinctive clinical, pathological and
      molecular features of colorectal cancer independently of microsatellite
      instability status.
AB  - BACKGROUND: BRAF is a member of RAF family of serine/threonine kinases and
      mediates cellular responses to growth signals through the RAS-RAF-MAP kinase
      pathway. Activating mutations in BRAF have recently been found in about 10% of
      colorectal cancers, with the vast majority being a V600E hotspot mutation. The
      aim of the present study was to evaluate the clinical, pathological and molecular
      phenotype of colorectal tumors with BRAF mutations. RESULTS: Mutations in BRAF
      were identified in 8% (23/275) of colorectal cancers. They were 5-10-fold more
      frequent in tumors with infiltrating lymphocytes, location in the proximal colon,
      poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with
      BRAF mutation were also 10-fold more likely to show microsatellite instability
      and frequent DNA methylation (P < 0.0001) compared to tumors without this
      mutation. The characteristic morphological features of tumors with BRAF mutation
      (infiltrating lymphocytes, poor grade, mucinous) remained after stratification
      according to microsatellite instability and methylator phenotypes. Mutations in
      BRAF were mutually exclusive with mutations in KRAS but showed no clear
      association with the presence of TP53 mutation. CONCLUSION: BRAF mutation
      identifies a colorectal cancer subgroup with distinctive phenotypic properties
      independent of microsatellite instability status and thus could be a valuable
      marker for studies into the clinical properties of these tumors.

PMID- 16403225
TI  - How sulfadoxine-pyrimethamine (SP) was perceived in some rural communities after
      phasing out chloroquine (CQ) as a first-line drug for uncomplicated malaria in
      Tanzania: lessons to learn towards moving from monotherapy to fixed combination
      therapy.
AB  - Malaria is a leading cause of death in Sub-Saharan Africa. Tanzania changed its
      malaria treatment policy from chloroquine (CQ) to Sulphadoxine-Pyrimethamine (SP)
      as first line drug in August 2001. We wanted to assess the perception and
      behaviour about SP after phasing out chloroquine which was very popular, cheap,
      available, and was preferred by many people for self-medication in homes as it
      was considered to have minimal side effects. Focus Group Discussions (FGDs) were
      carried out after one year of the anti-malarial drug treatment policy change in
      the country. The FGD themes were on malaria for under-five children and other age
      groups, anti-malarial drug use through self-medications, specific experiences
      people had about SP drug for both mothers/guardians, men in the communities and
      health workers. A total of twelve FGDs were performed with mothers/guardians, men
      and health workers in the selected public health care facilities in the district.
      In the FGDs people feared adverse reactions from SP; its slow ability of reducing
      fever and self-treatment in this case was less reported from the
      mothers/guardians groups. However, SP was reported by health workers to be
      administered using the direct observation approach under supervision in their
      health care facilities. This was done in order to increase compliance as there
      were worries that some mothers were throwing away the drug if they were
      instructed by health workers to go and administer SP to their sick children at
      home. Based on this information, it is obvious that fear and negative perceptions
      about SP drug was common in the study setting. As evidence of this, there was
      less reported home-stocking and self-medication in the discussions for this
      particular recommended new first-line anti-malarial. The public has demonstrated
      a lack of confidence in SP. Furthermore, some health workers expressed obvious
      fear and negative perceptions towards the drug despite the fact that some FGDs
      with health workers considered the drug to be good and effective against malaria.
      Such negative perception towards SP highlights the need to start earlier
      sensitization and educational campaigns to the rural communities for a new drug
      program to ensure its success. Messages should clearly state what should be
      expected from the new drug (Coartem), before its introduction. This is important
      especially as Tanzania is expected to move towards the expensive but efficacious
      and effective fixed-combination (Coartem) anti-malarial therapy early next year
      (2006).

PMID- 16403226
TI  - Stable low-level expression of p21WAF1/CIP1 in A549 human bronchogenic carcinoma
      cell line-derived clones down-regulates E2F1 mRNA and restores cell proliferation
      control.
AB  - BACKGROUND: Deregulated cell cycle progression and loss of proliferation control
      are key properties of malignant cells. In previous studies, an interactive
      transcript abundance index (ITAI) comprising three cell cycle control genes, [MYC
      x E2F1]/p21 accurately distinguished normal from malignant bronchial epithelial
      cells (BEC), using a cut-off threshold of 7,000. This cut-off is represented by a
      line with a slope of 7,000 on a bivariate plot of p21 versus [MYC x E2F1], with
      malignant BEC above the line and normal BEC below the line. This study was an
      effort to better quantify, at the transcript abundance level, the difference
      between normal and malignant BEC. The hypothesis was tested that experimental
      elevation of p21 in a malignant BEC line would decrease the value of the [MYC x
      E2F1]/p21 ITAI to a level below this line, resulting in loss of immortality and
      limited cell population doubling capacity. In order to test the hypothesis, a p21
      expression vector was transfected into the A549 human bronchogenic carcinoma cell
      line, which has low constitutive p21 TA expression relative to normal BEC.
      RESULTS: Following transfection of p21, four A549/p21 clones with stable two-fold
      up-regulated p21 expression were isolated and expanded. For each clone, the
      increase in p21 transcript abundance (TA) was associated with increased total p21
      protein level, more than 5-fold reduction in E2F1 TA, and 10-fold reduction in
      the [MYC x E2F1]/p21 ITAI to a value below the cut-off threshold. These changes
      in regulation of cell cycle control genes were associated with restoration of
      cell proliferation control. Specifically, each transfectant was capable of only
      15 population doublings compared with unlimited population doublings for parental
      A549. This change was associated with an approximate 2-fold increase in
      population doubling time to 38.4 hours (from 22.3 hrs), resumption of contact
      inhibition, and reduced dividing cell fraction as measured by flow cytometric DNA
      analysis. CONCLUSION: These results, likely due to increased p21-mediated down
      regulation of E2F1 TA at the G1/S phase transition, are consistent with our
      hypothesis. Specifically, they provide experimental confirmation that a line with
      slope of 7,000 on the p21 versus [MYC x E2F1] bivariate plot quantifies the
      difference between normal and malignant BEC at the level of transcript abundance.

PMID- 16403227
TI  - Alpha-gliadin genes from the A, B, and D genomes of wheat contain different sets
      of celiac disease epitopes.
AB  - BACKGROUND: Bread wheat (Triticum aestivum) is an important staple food. However,
      wheat gluten proteins cause celiac disease (CD) in 0.5 to 1% of the general
      population. Among these proteins, the alpha-gliadins contain several peptides
      that are associated to the disease. RESULTS: We obtained 230 distinct alpha
      gliadin gene sequences from severaldiploid wheat species representing the
      ancestral A, B, and D genomes of the hexaploid bread wheat. The large majority of
      these sequences (87%) contained an internal stop codon. All alpha-gliadin
      sequences could be distinguished according to the genome of origin on the basis
      of sequence similarity, of the average length of the polyglutamine repeats, and
      of the differences in the presence of four peptides that have been identified as
      T cell stimulatory epitopes in CD patients through binding to HLA-DQ2/8. By
      sequence similarity, alpha-gliadins from the public database of hexaploid T.
      aestivum could be assigned directly to chromosome 6A, 6B, or 6D. T. monococcum (A
      genome) sequences, as well as those from chromosome 6A of bread wheat, almost
      invariably contained epitope glia-alpha9 and glia-alpha20, but never the intact
      epitopes glia-alpha and glia-alpha2. A number of sequences from T. speltoides, as
      well as a number of sequences fromchromosome 6B of bread wheat, did not contain
      any of the four T cell epitopes screened for. The sequences from T. tauschii (D
      genome), as well as those from chromosome 6D of bread wheat, were found to
      contain all of these T cell epitopes in variable combinations per gene. The
      differences in epitope composition resulted mainly from point mutations. These
      substitutions appeared to be genome specific. CONCLUSION: Our analysis shows that
      alpha-gliadin sequences from the three genomes of bread wheat form distinct
      groups. The four known T cell stimulatory epitopes are distributed non-randomly
      across the sequences, indicating that the three genomes contribute differently to
      epitope content. A systematic analysis of all known epitopes in gliadins and
      glutenins will lead to better understanding of the differences in toxicity among
      wheat varieties. On the basis of such insight, breeding strategies can be
      designed to generate less toxic varieties of wheat which may be tolerated by at
      least part of the CD patient population.

PMID- 16403228
TI  - Utilization of two sample t-test statistics from redundant probe sets to evaluate
      different probe set algorithms in GeneChip studies.
AB  - BACKGROUND: The choice of probe set algorithms for expression summary in a
      GeneChip study has a great impact on subsequent gene expression data analysis.
      Spiked-in cRNAs with known concentration are often used to assess the relative
      performance of probe set algorithms. Given the fact that the spiked-in cRNAs do
      not represent endogenously expressed genes in experiments, it becomes
      increasingly important to have methods to study whether a particular probe set
      algorithm is more appropriate for a specific dataset, without using such external
      reference data. RESULTS: We propose the use of the probe set redundancy feature
      for evaluating the performance of probe set algorithms, and have presented three
      approaches for analyzing data variance and result bias using two sample t-test
      statistics from redundant probe sets. These approaches are as follows: 1)
      analyzing redundant probe set variance based on t-statistic rank order, 2)
      computing correlation of t-statistics between redundant probe sets, and 3)
      analyzing the co-occurrence of replicate redundant probe sets representing
      differentially expressed genes. We applied these approaches to expression summary
      data generated from three datasets utilizing individual probe set algorithms of
      MAS5.0, dChip, or RMA. We also utilized combinations of options from the three
      probe set algorithms. We found that results from the three approaches were
      similar within each individual expression summary dataset, and were also in good
      agreement with previously reported findings by others. We also demonstrate the
      validity of our findings by independent experimental methods. CONCLUSION: All
      three proposed approaches allowed us to assess the performance of probe set
      algorithms using the probe set redundancy feature. The analyses of redundant
      probe set variance based on t-statistic rank order and correlation of t
      statistics between redundant probe sets provide useful tools for data variance
      analysis, and the co-occurrence of replicate redundant probe sets representing
      differentially expressed genes allows estimation of result bias. The results also
      suggest that individual probe set algorithms have dataset-specific performance.

PMID- 16403229
TI  - Potential community and public health impacts of medically supervised safer
      smoking facilities for crack cocaine users.
AB  - There is growing evidence of the public health and community harms associated
      with crack cocaine smoking, particularly the risk of blood-borne transmission
      through non-parenteral routes. In response, community advocates and policy makers
      in Vancouver, Canada are calling for an exemption from Health Canada to pilot a
      medically supervised safer smoking facility (SSF) for non-injection drug users
      (NIDU). Current reluctance on the part of health authorities is likely due to the
      lack of existing evidence surrounding the extent of related harm and potential
      uptake of such a facility among NIDUs in this setting. In November 2004, a
      feasibility study was conducted among 437 crack cocaine smokers. Univariate
      analyses were conducted to determine associations with willingness to use a SSF
      and logistic regression was used to adjust for potentially confounding variables
      (p < 0.05). Variables found to be independently associated with willingness to
      use a SSF included recent injection drug use (OR = 1.72, 95% CI: 1.09-2.70),
      having equipment confiscated or broken by police (OR = 1.96, 95% CI: 1.24-2.85),
      crack bingeing (OR = 2.16, 95% CI: 1.39-3.12), smoking crack in public places (OR
      = 2.48, 95% CI: 1.65-3.27), borrowing crack pipes (OR = 2.50, 95% CI: 1.86-3.40),
      and burns/inhaled brillo due to rushing smoke in public places (OR = 4.37, 95%
      CI: 2.71-8.64). The results suggest a strong potential for a SSF to reduce the
      health related harms and address concerns of public order and open drug use among
      crack cocaine smokers should a facility be implemented in this setting.

PMID- 16403230
TI  - The comparative burden of salmonellosis in the European Union member states,
      associated and candidate countries.
AB  - BACKGROUND: Salmonella is an infectious agents causing numerous cases of illness
      each year, and thereby having significant economic impact. Using returning
      Swedish travellers we estimated the burden of salmonellosis in different European
      countries. METHODS: From the Swedish database on notifiable communicable diseases
      15,864 cases with travel-associated salmonellosis acquired in Europe from 1997
      2003 were retrieved. These cases were compared to a dataset from the same years
      on 14,171 randomly selected Swedish residents, with a history of recent overnight
      travel in Europe. Distribution of salmonellosis in returning travellers and the
      distribution of Salmonella Enteritidis was analysed for different member states
      in the European Union, associated and candidate countries. The risk of being
      notified with a salmonella infection after return from each European
      country/region was calculated, and compared with official reporting data rom
      these countries. Using Norway as reference country, we could 1) construct
      comparable incidence estimates and 2) calculate the "under-reporting" in each
      country compared to Norway. RESULTS: The highest burden of salmonellosis was
      estimated for Bulgaria (2741/100,000), followed by Turkey with 2344/100,000 and
      Malta with 2141/100,000. S. Enteritidis is the dominating serotype, 66.9 % of all
      cases and phage type 4 accounts for 37.5 % of the S. Enteritidis cases.
      CONCLUSION: Using returning tourists as a sentinel population can provide a
      useful base for comparison of disease burdens in different countries/regions.
      Focusing prevention of salmonellosis to prevention of egg and poultry associated
      S. Enteritidis infection will have a major impact from a public health
      perspective and will significantly lower the burden of disease in most European
      countries.

PMID- 16403231
TI  - Integration of Myeloblastosis Associated Virus proviral sequences occurs in the
      vicinity of genes encoding signaling proteins and regulators of cell
      proliferation.
AB  - AIMS: Myeloblastosis Associated Virus type 1 (N) [MAV 1(N)] induces specifically
      nephroblastomas in 8-10 weeks when injected to newborn chicken. The MAV-induced
      nephroblastomas constitute a unique animal model of the pediatric Wilms' tumor.
      We have made use of three independent nephroblastomas that represent increasing
      tumor grades, to identify the host DNA regions in which MAV proviral sequences
      were integrated. METHODS: Cellular sequences localized next to MAV-integration
      sites in the tumor DNAs were used to screen a Bacterial Artificial Chromosomes
      (BACs) library and isolate BACs containing about 150 kilobases of normal DNA
      corresponding to MAV integration regions (MIRs). These BACs were mapped on the
      chicken chromosomes by Fluorescent In Situ Hybridization (FISH) and used for
      molecular studies. RESULTS: The different MAV integration sites that were
      conserved after tumor cell selection identify genes involved in the control of
      cell signaling and proliferation. Syntenic fragments in human DNA contain genes
      whose products have been involved in normal and pathological kidney development,
      and several oncogenes responsible for tumorigenesis in human. CONCLUSION: The
      identification of putative target genes for MAV provides important clues for the
      understanding of the MAV pathogenic potential. These studies identified ADAMTS1
      as a gene upregulated in MAV-induced nephroblastoma and established that ccn3/nov
      is not a preferential site of integration for MAV as previously thought. The
      present results support our hypothesis that the highly efficient and specific MAV
      induced tumorigenesis results from the alteration of multiple target genes in
      differentiating blastemal cells, some of which are required for the progression
      to highly aggressive stages. This study reinforces our previous conclusions that
      the MAV-induced nephroblastoma constitutes an excellent model in which to
      characterize new potential oncogenes and tumor suppressors involved in the
      establishment and maintenance of tumors.

PMID- 16403232
TI  - Muscle fiber-type distribution predicts weight gain and unfavorable left
      ventricular geometry: a 19 year follow-up study.
AB  - BACKGROUND: Skeletal muscle consists of type-I (slow-twitch) and type-II (fast
      twitch) fibers, with proportions highly variable between individuals and mostly
      determined by genetic factors. Cross-sectional studies have associated low
      percentage of type-I fibers (type-I%) with many cardiovascular risk factors.
      METHODS: We investigated whether baseline type-I% predicts left ventricular (LV)
      structure and function at 19-year follow-up, and if so, which are the strongest
      mediating factors. At baseline in 1984 muscle fiber-type distribution (by
      actomyosin ATPase staining) was studied in 63 healthy men (aged 32-58 years). The
      follow-up in 2003 included echocardiography, measurement of obesity related
      variables, physical activity and blood pressure. RESULTS: In the 40 men not using
      cardiovascular drugs at follow-up, low type-I% predicted higher heart rate, blood
      pressure, and LV fractional shortening suggesting increased sympathetic tone. Low
      type-I% predicted smaller LV chamber diameters (P < or = 0.009) and greater
      relative wall thickness (P = 0.034) without increase in LV mass (concentric
      remodeling). This was explained by the association of type-I% with obesity
      related variables. Type-I% was an independent predictor of follow-up body fat
      percentage, waist/hip ratio, weight gain in adulthood, and physical activity (in
      all P < or = 0.001). After including these risk factors in the regression models,
      weight gain was the strongest predictor of LV geometry explaining 64% of the
      variation in LV end-diastolic diameter, 72% in end-systolic diameter, and 53% in
      relative wall thickness. CONCLUSION: Low type-I% predicts obesity and weight gain
      especially in the mid-abdomen, and consequently unfavourable LV geometry
      indicating increased cardiovascular risk.

PMID- 16403234
TI  - Comparison of isocaloric very low carbohydrate/high saturated fat and high
      carbohydrate/low saturated fat diets on body composition and cardiovascular risk.
AB  - BACKGROUND: It is speculated that high saturated fat very low carbohydrate diets
      (VLCARB) have adverse effects on cardiovascular risk but evidence for this in
      controlled studies is lacking. The objective of this study was to compare, under
      isocaloric conditions, the effects of a VLCARB to 2 low saturated fat high
      carbohydrate diets on body composition and cardiovascular risk. METHODS: Eighty
      three subjects, 48 +/- 8 y, total cholesterol 5.9 +/- 1.0 mmol/L, BMI 33 +/- 3
      kg/m2 were randomly allocated to one of 3 isocaloric weight loss diets (6 MJ) for
      8 weeks and on the same diets in energy balance for 4 weeks: Very Low Fat (VLF)
      (CHO:Fat:Protein; %SF = 70:10:20; 3%), High Unsaturated Fat (HUF) = (50:30:20;
      6%), VLCARB (4:61:35; 20%) RESULTS: Percent fat mass loss was not different
      between diets VLCARB -4.5 +/- 0.5, VLF-4.0 +/- 0.5, HUF -4.4 +/- 0.6 kg). Lean
      mass loss was 32-31% on VLCARB and VLF compared to HUF (21%) (P < 0.05). LDL-C
      increased significantly only on VLCARB by 7% (p < 0.001 compared with the other
      diets) but apoB was unchanged on this diet and HDL-C increased relative to the
      other 2 diets. Triacylglycerol was lowered by 0.73 +/- 0.12 mmol/L on VLCARB
      compared to -0.15 +/- 0.07 mmol/L on HUF and -0.06 +/- 0.13 mmol/L on VLF (P <
      0.001). Plasma homocysteine increased 6.6% only on VLCARB (P = 0.026). VLCARB
      lowered fasting insulin 33% compared to a 19% fall on HUF and no change on VLF (P
      < 0.001). The VLCARB meal also provoked significantly lower post prandial glucose
      and insulin responses than the VLF and HUF meals. All diets decreased fasting
      glucose, blood pressure and CRP (P < 0.05). CONCLUSION: Isocaloric VLCARB results
      in similar fat loss than diets low in saturated fat, but are more effective in
      improving triacylglycerols, HDL-C, fasting and post prandial glucose and insulin
      concentrations. VLCARB may be useful in the short-term management of subjects
      with insulin resistance and hypertriacylglycerolemia.

PMID- 16403233
TI  - A comparison of oral omeprazole and intravenous cimetidine in reducing
      complications of duodenal peptic ulcer.
AB  - BACKGROUND: Gastrointestinal bleeding is a common problem and its most common
      etiology is peptic ulcer disease. Ulcer rebleeding is considered a perilous
      complication for patients. To reduce the rate of rebleeding and to fasten the
      improvement of patients' general conditions, most emergency departments in Iran
      use H2-blockers before endoscopic procedures (i.e. intravenous omeprazole is not
      available in Iran). The aim of this study was to compare therapeutic effects of
      oral omeprazole and intravenous cimetidine on reducing rebleeding rates, duration
      of hospitalization, and the need for blood transfusion in duodenal ulcer
      patients. METHODS: In this clinical trial, 80 patients with upper
      gastrointestinal bleeding due to duodenal peptic ulcer and endoscopic evidence of
      rebleeding referring to emergency departments of Imam and Sina hospitals in
      Tabriz, Iran were randomly assigned to two equal groups; one was treated with
      intravenous cimetidine 800 mg per day and the other, with 40 mg oral omeprazole
      per day. RESULTS: No statistically significant difference was found between
      cimetidine and omeprazole groups in regards to sex, age, alcohol consumption,
      cigarette smoking, NSAID consumption, endoscopic evidence of rebleeding, mean
      hemoglobin and mean BUN levels on admission, duration of hospitalization and the
      mean time of rebleeding. However, the need for blood transfusion was much lower
      in omeprazole than in cimetidine group (mean: 1.68 versus 3.58 units,
      respectively; p < 0.003). Moreover, rebleeding rate was significantly lower in
      omeprazole group (15%) than in cimetidine group (50%) (p < 0.001). CONCLUSION:
      This study demonstrated that oral omeprazole significantly excels intravenous
      cimetidine in reducing the need for blood transfusion and lowering rebleeding
      rates in patients with upper gastrointestinal bleeding. Though not statistically
      significant (p = 0.074), shorter periods of hospitalization were found for
      omeprazole group which merits consideration for cost minimization.

PMID- 16403235
TI  - Profit and loss analysis for an intensive care unit (ICU) in Japan: a tool for
      strategic management.
AB  - BACKGROUND: Accurate cost estimate and a profit and loss analysis are necessary
      for health care practice. We performed an actual financial analysis for an
      intensive care unit (ICU) of a university hospital in Japan, and tried to discuss
      the health care policy and resource allocation decisions that have an impact on
      critical intensive care. METHODS: The costs were estimated by a department level
      activity based costing method, and the profit and loss analysis was based on a
      break-even point analysis. The data used included the monthly number of patients,
      the revenue, and the direct and indirect costs of the ICU in 2003. RESULTS: The
      results of this analysis showed that the total costs of USD 2,678,052 of the ICU
      were mainly incurred due to direct costs of 88.8%. On the other hand, the actual
      annual total patient days in the ICU were 1,549 which resulted in revenues of USD
      2,295,044. However, it was determined that the ICU required at least 1,986
      patient days within one fiscal year based on a break-even point analysis. As a
      result, an annual deficit of USD 383,008 has occurred in the ICU. CONCLUSION:
      These methods are useful for determining the profits or losses for the ICU
      practice, and how to evaluate and to improve it. In this study, the results
      indicate that most ICUs in Japanese hospitals may not be profitable at the
      present time. As a result, in order to increase the income to make up for this
      deficit, an increase of 437 patient days in the ICU in one fiscal year is needed,
      and the number of patients admitted to the ICU should thus be increased without
      increasing the number of beds or staff members. Increasing the number of patients
      referred from cooperating hospitals and clinics therefore appears to be the best
      strategy for achieving these goals.

PMID- 16403236
TI  - Prevalence of inappropriate medication using Beers criteria in Japanese long-term
      care facilities.
AB  - BACKGROUND: The prevalence and risk factors of potentially inappropriate
      medication use among the elderly patients have been studied in various countries,
      but because of the difficulty of obtaining data on patient characteristics and
      medications they have not been studied in Japan. METHODS: We conducted a
      retrospective cross-sectional study in 17 Japanese long-term care (LTC)
      facilities by collecting data from the comprehensive MDS assessment forms for
      1669 patients aged 65 years and over who were assessed between January and July
      of 2002. Potentially inappropriate medications were identified on the basis of
      the 2003 Beers criteria. RESULTS: The patients in the sample were similar in
      terms of demographic characteristics to those in the national survey. Our study
      revealed that 356 (21.1%) of the patients were treated with potentially
      inappropriate medication independent of disease or condition. The most commonly
      inappropriately prescribed medication was ticlopidine, which had been prescribed
      for 107 patients (6.3%). There were 300 (18.0%) patients treated with at least 1
      inappropriate medication dependent on the disease or condition. The highest
      prevalence of inappropriate medication use dependent on the disease or condition
      was found in patients with chronic constipation. Multiple logistic regression
      analysis revealed psychotropic drug use (OR = 1.511), medication cost of per day
      (OR = 1.173), number of medications (OR = 1.140), and age (OR = 0.981) as factors
      related to inappropriate medication use independent of disease or condition.
      Neither patient characteristics nor facility characteristics emerged as
      predictors of inappropriate prescription. CONCLUSION: The prevalence and
      predictors of inappropriate medication use in Japanese LTC facilities were
      similar to those in other countries.

PMID- 16403237
TI  - Inhaled nitric oxide alleviates hyperoxia suppressed phosphatidylcholine
      synthesis in endotoxin-induced injury in mature rat lungs.
AB  - BACKGROUND: We investigated efficacy of inhaled nitric oxide (NO) in modulation
      of metabolism of phosphatidylcholine (PC) of pulmonary surfactant and in anti
      inflammatory mechanism of mature lungs with inflammatory injury. METHODS: Healthy
      adult rats were divided into a group of lung inflammation induced by i.v.
      lipopolysaccharides (LPS) or a normal control (C) for 24 h, and then exposed to:
      room air (Air), 95% oxygen (O), NO (20 parts per million, NO), both O and NO
      (ONO) as subgroups, whereas [3H]-choline was injected i.v. for incorporation into
      PC of the lungs which were processed subsequently at 10 min, 4, 8, 12 and 24 h,
      respectively, for measurement of PC synthesis and proinflammatory cytokine
      production. RESULTS: LPS-NO subgroup had the lowest level of labeled PC in total
      phospholipids and disaturated PC in bronchoalveolar lavage fluid and lung tissue
      (decreased by 46-59%), along with the lowest activity of cytidine triphosphate:
      phosphocholine cytidylyltransferase (-14-18%) in the lungs, compared to all other
      subgroups at 4 h (p < 0.01), but not at 8 and 12 h. After 24-h, all LPS-subgroups
      had lower labeled PC than the corresponding C-subgroups (p < 0.05). LPS-ONO had
      higher labeled PC in total phospholipids and disaturated PC, activity of
      cytidylyltransferase, and lower activity of nuclear transcription factor-kappaB
      and expression of proinflammatory cytokine mRNA, than that in the LPS-O subgroup
      (p < 0.05). CONCLUSION: In LPS-induced lung inflammation in association with
      hyperoxia, depressed PC synthesis and enhanced proinflammatory cytokine
      production may be alleviated by iNO. NO alone only transiently suppressed the PC
      synthesis as a result of lower activity of cytidylyltransferase.

PMID- 16403238
TI  - Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML
      database--Xindice.
AB  - BACKGROUND: Many proteomics initiatives require integration of all information
      with uniformcriteria from collection of samples and data display to publication
      of experimental results. The integration and exchanging of these data of
      different formats and structure imposes a great challenge to us. The XML
      technology presents a promise in handling this task due to its simplicity and
      flexibility. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in
      southern China and Southeast Asia, which has marked geographic and racial
      differences in incidence. Although there are some cancer proteome databases now,
      there is still no NPC proteome database. RESULTS: The raw NPC proteome experiment
      data were captured into one XML document with Human Proteome Markup Language (HUP
      ML) editor and imported into native XML database Xindice. The 2D/MS repository of
      NPC proteome was constructed with Apache, PHP and Xindice to provide access to
      the database via Internet. On our website, two methods, keyword query and click
      query, were provided at the same time to access the entries of the NPC proteome
      database. CONCLUSION: Our 2D/MS repository can be used to share the raw NPC
      proteomics data that are generated from gel-based proteomics experiments. The
      database, as well as the PHP source codes for constructing users' own proteome
      repository, can be accessed at http://www.xyproteomics.org/.

PMID- 16403240
TI  - Impaired verbal self-monitoring in psychosis: effects of state, trait and
      diagnosis.
AB  - BACKGROUND: Cognitive models propose that auditory verbal hallucinations arise
      through defective self-monitoring and external attribution of inner speech. We
      used a paradigm that engages verbal self-monitoring to examine how deficits in
      this process are related to symptoms and diagnosis in patients with psychosis.
      METHOD: We tested 45 patients with schizophrenia. Fifteen had current auditory
      hallucinations, 15 had a history of (but no current) auditory hallucinations, and
      15 had delusions but neither current nor previous hallucinations. We also tested
      10 patients with affective psychosis and current auditory hallucinations, and 20
      healthy volunteers. Participants read single adjectives aloud while the source
      and the pitch of the on-line auditory verbal feedback was manipulated, then
      immediately identified the source of the speech they heard
      ('self'/'other'/'unsure'). RESULTS: When reading aloud with distorted feedback of
      their own voice, patients with schizophrenia who had auditory hallucinations were
      more likely than controls to misidentify its source as 'other'. Patients with
      delusions but no current hallucinations displayed a similar deficit, although
      there was a trend for this to be less marked. Patients with a history of
      hallucinations did not differ from controls. Patients with hallucinations in the
      context of an affective disorder made more unsure responses rather than
      misattributions. CONCLUSIONS: Difficulty with source monitoring was related to
      the acute psychotic state rather than a predisposition to hallucinations, and was
      evident in patients with affective psychosis as well as schizophrenia. External
      misattribution of source may reflect an impairment in verbal self-monitoring
      and/or the appraisal of ambiguous sensory material.

PMID- 16403239
TI  - Compound developmental eye disorders following inactivation of TGFbeta signaling
      in neural-crest stem cells.
AB  - BACKGROUND: Development of the eye depends partly on the periocular mesenchyme
      derived from the neural crest (NC), but the fate of NC cells in mammalian eye
      development and the signals coordinating the formation of ocular structures are
      poorly understood. RESULTS: Here we reveal distinct NC contributions to both
      anterior and posterior mesenchymal eye structures and show that TGFbeta signaling
      in these cells is crucial for normal eye development. In the anterior eye,
      TGFbeta2 released from the lens is required for the expression of transcription
      factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle
      structures of the eye that control intraocular pressure. TGFbeta enhances Foxc1
      and induces Pitx2 expression in cell cultures. As in patients carrying mutations
      in PITX2 and FOXC1, TGFbeta signal inactivation in NC cells leads to ocular
      defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the
      posterior eye, NC cell-specific inactivation of TGFbeta signaling results in a
      condition reminiscent of the human disorder persistent hyperplastic primary
      vitreous. As a secondary effect, retinal patterning is also disturbed in mutant
      mice. CONCLUSION: In the developing eye the lens acts as a TGFbeta signaling
      center that controls the development of eye structures derived from the NC.
      Defective TGFbeta signal transduction interferes with NC-cell differentiation and
      survival anterior to the lens and with normal tissue morphogenesis and patterning
      posterior to the lens. The similarity to developmental eye disorders in humans
      suggests that defective TGFbeta signal modulation in ocular NC derivatives
      contributes to the pathophysiology of these diseases.

PMID- 16403241
TI  - Thought disorder in schizophrenia is associated with both executive dysfunction
      and circumscribed impairments in semantic function.
AB  - BACKGROUND: Formal thought disorder (FTD) has long been regarded as a key sign of
      schizophrenia but little is known about its origins or aetiology. One suggestion
      is that it is directly related to disordered language functioning; a second is
      that it is a reflection of poor neurocognitive functioning. A current model
      posits that it is related to a combination of executive dysfunction and impaired
      semantic processing. METHOD: To examine these alternative ideas, a heterogeneous
      group of 30 patients, all carrying a diagnosis of schizophrenia, and 18 non
      patient controls completed a series of neurocognitive and psycholinguistic tests,
      and a clinical review that, inter alia, permitted assessment of thought disorder
      (TD) using the Thought, Language and Communication Scale (TLC). RESULTS: Patients
      generally performed at a lower level on most components of the test battery, but
      there was little evidence of a relationship between TD and syntactic
      psycholinguistic function. However, schizophrenic patients manifesting higher
      levels of TD performed at a lower level on tests sensitive to executive
      dysfunction and semantic impairments. CONCLUSIONS: The origins of TD seem more
      closely linked to deficits in executive functioning and semantic processing than
      to impairments in other language functions or general cognition.

PMID- 16403242
TI  - Evidence that the outcome of developmental expression of psychosis is worse for
      adolescents growing up in an urban environment.
AB  - BACKGROUND: The urban environment may increase the risk for psychotic disorder in
      interaction with pre-existing risk for psychosis, but direct confirmation has
      been lacking. The hypothesis was examined that the outcome of subclinical
      expression of psychosis during adolescence, as an indicator of psychosis
      proneness, would be worse for those growing up in an urban environment, in terms
      of having a greater probability of psychosis persistence over a 3.5-year period.
      METHOD: A cohort of 918 adolescents from the Early Developmental Stages of
      Psychopathology Study (EDSP), aged 14-17 years (mean 15.1 years), growing up in
      contrasting urban and non-urban environments, completed a self-report measure of
      psychotic symptoms at baseline (Baseline Psychosis) and at first follow-up around
      1 year post-baseline (T1). They were again interviewed by trained psychologists
      for the presence of psychotic symptoms at the second follow-up on average 3.5
      years post-baseline (T2). RESULTS: The rate of T2 psychotic symptoms was 14.2% in
      those exposed to neither Baseline Psychosis nor Urbanicity, 12.1% in those
      exposed to Urbanicity alone, 14.9% in those exposed to Baseline Psychosis alone
      and 29.0% in those exposed to both Baseline Psychosis and Urbanicity. The odds
      ratio (OR) for the combined exposure was 2.46 [95% confidence interval (CI) 1.46
      4.14], significantly greater than that expected if Urbanicity and Baseline
      Psychosis acted independently. CONCLUSION: These findings support the suggestion
      that the outcome of the developmental expression of psychosis is worse in urban
      environments. The environment may impact on risk for psychotic disorder by
      causing an abnormal persistence of a developmentally common expression of
      psychotic experiences.

PMID- 16403243
TI  - Incremental cost-effectiveness of a collaborative care intervention for panic
      disorder.
AB  - BACKGROUND: Panic disorder is a prevalent, often disabling, disorder among
      primary-care patients, but there are large gaps in quality of treatment in
      primary care. This study describes the incremental cost-effectiveness of a
      combined cognitive behavioral therapy (CBT) and pharmacotherapy intervention for
      patients with panic disorder versus usual primary-care treatment. METHOD: This
      randomized control trial recruited 232 primary-care patients meeting DSM-IV
      criteria for panic disorder from March 2000 to March 2002 from six primary-care
      clinics from university-affiliated clinics at the University of Washington
      (Seattle) and University of California (Los Angeles and San Diego). Patients were
      randomly assigned to receive either treatment as usual or a combined CBT and
      pharmacotherapy intervention for panic disorder delivered in primary care by a
      mental health therapist. Intervention patients had up to six sessions of CBT
      modified for the primary-care setting in the first 12 weeks, and up to six
      telephone follow-ups over the next 9 months. The primary outcome variables were
      total out-patient costs, anxiety-free days (AFDs) and quality adjusted life-years
      (QALYs). RESULTS: Relative to usual care, intervention patients experienced 60.4
      [95% confidence interval (CI) 42.9-77.9] more AFDs over a 12-month period. Total
      incremental out-patient costs were 492 US dollars higher (95% CI 236-747 US
      dollars ) in intervention versus usual care patients with a cost per additional
      AFD of 8.40 US dollars (95% CI 2.80-14.0 US dollars ) and a cost per QALY ranging
      from 14,158 US dollars (95% CI 6,791-21,496 US dollars ) to 24,776 US dollars
      (95% CI 11,885-37,618 US dollars ). The cost per QALY estimate is well within the
      range of other commonly accepted medical interventions such as statin use and
      treatment of hypertension. CONCLUSIONS: The combined CBT and pharmacotherapy
      intervention was associated with a robust clinical improvement compared to usual
      care with a moderate increase in ambulatory costs.

PMID- 16403244
TI  - Deaths from all causes in a long-term follow-up study of 11,583 deliberate self
      harm patients.
AB  - BACKGROUND: Deliberate self-harm (DSH) may be associated with increased risk of
      death from a variety of causes, not just suicide. METHOD: A follow-up study of
      11,583 DSH patients who presented to a general hospital over a 20-year period was
      conducted to examine risk of death from a range of causes during a follow-up
      period of between 3 and 23 years. Deaths were identified through national death
      registries. Expected numbers of deaths were calculated from national death
      statistics. RESULTS: The number of deaths (1,185, 10.2%) was 2.2 times the
      expected number, the excess being significantly greater in males than females.
      Suicides were 17 times more frequent than expected and undetermined causes of
      death and accidental poisonings 15 times more frequent. Significantly more than
      expected numbers of deaths from most natural causes were found, including
      respiratory disease, circulatory, neurological, endocrine, digestive, skin and
      musculoskeletal and connective tissue disorders, and symptoms, signs and ill
      defined conditions. Deaths due to accidents other than poisoning were more
      frequent than expected in both genders and homicides more frequent in males.
      CONCLUSIONS: In addition to increased risk of suicide, DSH patients are at
      increased risk of dying from a wide range of other causes. Possible explanations
      include lifestyle factors, physical disorders contributing to initial risk of
      DSH, and social disadvantage. The findings are relevant to clinical management
      and evaluation of outcome and health-care costs associated with DSH.

PMID- 16403245
TI  - The act of diagnosis: pros and cons of labelling chronic fatigue syndrome.
AB  - BACKGROUND: One of the many controversies surrounding chronic fatigue syndrome
      (CFS) is the possible impact of the diagnostic label: is it disabling or
      enabling? In this paper, we discuss the pros and cons of labelling CFS. METHOD: A
      narrative synthesis of the literature. RESULTS: Diagnosed CFS patients have a
      worse prognosis than fatigue syndrome patients without such a label. The ways in
      which CFS patients perceive themselves, label their symptoms and appraise
      stressors may perpetuate or exacerbate their symptoms, a process that involves
      psychological, psychosocial and cultural factors. Labels can also lead to
      conflicts with doctors who fear diagnosis might lead to worse outcomes. However,
      on the other hand, finding a label that fits one's condition can provide meaning,
      emotional relief and recognition, whilst the denial of the diagnosis of CFS in
      those who have already reached their own conclusion can be very counter
      productive. The act of diagnosis therefore seems to be a trade-off between
      empowerment, illness validation and group support, contrasted with the risk of
      diagnosis as self-fulfilling prophecy of non-recovery. CONCLUSIONS: The answer to
      the question of 'to label or not to label' may turn out to depend not on the
      label, but on what that label implies. It is acceptable and often beneficial to
      make diagnoses such as CFS, provided that this is the beginning, and not the end,
      of the therapeutic encounter.

PMID- 16403246
TI  - Impact of cognitive impairment on mild dementia patients and mild cognitive
      impairment patients and their informants.
AB  - BACKGROUND: The aim of this study was to identify key aspects of the impact of
      cognitive impairment on patients with mild cognitive impairment (MCI) and mild
      probable Alzheimer disease (AD) and their informants, and identify overlap and
      differences between the groups. METHODS: Structured focus group discussions were
      conducted with MCI patients, AD patients, MCI informants, and AD informants.
      Participants were recruited from memory clinics in the U.K. and the U.S.A. A
      total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated.
      Sessions were content reviewed to identify key impacts of cognitive impairment;
      results were compared across diagnostic groups and for patients and informants.
      RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change
      in social and family roles, embarrassment and shame, emotionality, insight, and
      burden. Patients were able to discuss the impact of cognitive impairment on their
      lives and reported frustration with recognized memory problems, diminished self
      confidence, fear of embarrassment, concerns about changing family roles due to
      cognitive impairment, and anxiety. Informants reported more symptoms and more
      impairment than did patients and indicated increased dependence on others among
      patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives
      and the lives of those close to them.

PMID- 16403247
TI  - Kimberley Indigenous Cognitive Assessment tool (KICA): development of a cognitive
      assessment tool for older indigenous Australians.
AB  - BACKGROUND: Indigenous Australians have a unique cultural heritage dating back
      many thousands of years. Unfortunately, there is no validated tool to assess
      cognition in older indigenous Australians. This study was designed to address
      this deficiency. The Kimberley Indigenous Cognitive Assessment (KICA) was
      developed with Indigenous health and aged care organizations, and comprises
      cognitive, informant and functional sections. The psychometric properties of the
      cognitive assessment section (KICA-Cog) are described in this paper. METHODS: The
      KICA-Cog was tested in 70 indigenous subjects, of varying cognitive abilities and
      diagnoses, over 45 years of age. Subjects were interviewed using the KICA-Cog and
      then independently assessed by expert clinical raters using DSM-IV and ICD-10
      criteria. Interrater and internal reliability were determined. RESULTS: The KICA
      Cog score showed no systematic interrater difference; the mean was -0.07 (SD =
      1.83). Interrater reliability for 16 individual questions from the cognitive
      section revealed a kappa-value > or = 0.6 and intraclass correlations for 12
      questions. Internal consistency, as assessed by Cronbach's alpha, was 0.88. Three
      items on the cognitive score (pension week, recall and free recall) effectively
      discriminated 85-7% of dementia cases. Sensitivity and specificity were 90.6% and
      92.6%, respectively, using a cut-off score of 31/32. CONCLUSIONS: The KICA-Cog
      appears to be a reliable assessment tool for cognitive impairment in an
      Australian older traditionally living indigenous population.

PMID- 16403248
TI  - Validation of a new symptom impact questionnaire for mild to moderate cognitive
      impairment.
AB  - BACKGROUND: Patient-reported outcomes assessment enhances the understanding of
      disease impact in a range of disorders. At mild levels of cognitive impairment
      the patient perspective on functioning, behavior and symptoms can be particularly
      valuable for syndrome characterization when clinical and neuropsychological
      findings are limited. We have evaluated the psychometric performance of the 55
      item Patient-Reported Outcomes in Cognitive Impairment (PROCOG), a new patient
      reported measure, to measure mild to moderate cognitive impairment symptoms and
      their impact from the perspective of patients with dementia of the Alzheimer's
      type (DAT) and mild cognitive impairment (MCI). METHODS: The sample of 75 DAT
      patients, 78 MCI patients and 33 cognitively intact control subjects (> 64 years)
      was recruited through medical centers in the U.SA. Validity was assessed through
      correlation to the Quality of Life--Alzheimer's Disease (QOL-AD) and Centers for
      Epidemiologic Studies--Depression Scale (CES-D) and neuropsychological
      assessments (WAIS subscales and MMSE). RESULTS: PROCOG scores for MCI patients
      were generally intermediate between DAT and control subjects. Internal
      consistency and test-retest reliability were acceptable. Correlations with the
      CES-D and QOL-AD were in the moderate to high range; correlations with the
      neuropsychological measures were low to moderate. CONCLUSIONS: The PROCOG
      demonstrated good to excellent psychometric properties among a sample of older
      adults with MCI and DAT as well as cognitively intact older adult control
      subjects and provides a method for collecting unique information on the patient
      experience of cognitive impairment. Subscales permit focused evaluation of
      domains relevant to the patient's experience of cognitive impairment.

PMID- 16403249
TI  - Focal or generalized vascular brain damage and vulnerability to depression after
      stroke: a 1-year prospective follow-up study.
AB  - BACKGROUND: Both the lesion location hypothesis and the vascular depression
      hypothesis have been proposed to explain the high incidence of depression in
      stroke patients. However, research studying both hypotheses in a single cohort
      is, at present, scarce. OBJECTIVE: To test the independent effects of lesion
      location (left hemisphere, anterior region) and of co-occurring generalized
      vascular damage on the development of depression in the first year after ischemic
      stroke, while other risk factors for depression are controlled for. METHODS: One
      hundred and ninety consecutive patients with a first-ever, supratentorial infarct
      were followed up for one year. CT was performed in the acute phase of stroke,
      while in 75 patients an additional MRI scan was also available. Depression was
      assessed at 1, 3, 6, 9, and 12 months after stroke using self-rating scales as
      screening tools and the SCID-I to diagnose depression according to DSM-IV
      criteria. RESULTS: Separate analyses of the lesion location hypothesis and the
      vascular depression hypothesis failed to reveal significant support for either of
      these biological models of post-stroke depression. Similar negative results
      appeared from one overall, multivariate analysis including variables of both
      focal and generalized vascular brain damage, as well as other non-cerebral risk
      factors. In addition, level of handicap and neuroticism were independent
      predictors of depression in this cohort, as has been reported previously.
      CONCLUSION: This study supports neither the lesion location nor the vascular
      depression hypothesis of post-stroke depression. A biopsychosocial model
      including both premorbid (prior to stroke) vulnerability factors, such as
      neuroticism and (family) history of depression, as well as post-stroke stressors,
      such as level of handicap, may be more appropriate and deserves further study.

PMID- 16403250
TI  - The 2005 International Psychogeriatric Association (IPA) research awards in
      psychogeriatrics.

PMID- 16403251
TI  - [Apoptosis or necrosis, should which be expected for tumor cells?].
AB  - Evidence has indicated that low doses of anti-tumor regimens can induce cell
      apoptosis in vitro, although different regimens induce apoptosis by different
      mechanism and pathway. In recent years, new tumor treatment strategy has been
      mainly focused on inducing tumor cell apoptosis. The present review discusses the
      advantages and disadvantages of inducing tumor cell apoptosis. The benefit of
      inducing apoptosis is not to cause inflammatory reaction, but as its
      disadvantage, it inhibits immune responses, and the phagocytosis of apopotic
      bodies may result in horizontal transfer of genes (including oncogenes and other
      oncogenic materials), which can be one of the causes of tumor relapse. This paper
      proposes that the tumor treatment strategy should be turn into promoting tumor
      cell necrosis and inducing anti-tumor immune responses.

PMID- 16403252
TI  - [hCG-PLZF-RARalpha/hCG-RARalpha-PLZF transgenic mice developing into leukemia].
AB  - To investigate the potential role and the mechanism of PLZF-RARalpha/RARalpha
      PLZF double fusion gene in the pathogenesis of acute promyelocytic leukemia (APL)
      in vivo at systematic biological level, PLZF-RARalpha/RARalpha-PLZF double
      transgenic mouse model was established by intercross; the integration and
      expression of fusion genes were analyzed by PCR and RT-PCR; the disease phenotype
      was detected by morphological and pathological examination of peripheral blood
      and bone marrow cells, as well as flow cytometry assays; the effects of ATRA with
      or without tricostatin A on bone marrow blast cells from PLZF-RARalpha/RARalpha
      PLZF double TM were observed. The results showed that leukemia occurred in 5 PLZF
      RARalpha/RARalpha-PLZF double TM 7, 7, 9, 11 and 11 months respectively, out of
      them two (40%) with classic APL features, the others (60%) with chronic myeloid
      leukemia through an observation period of 18 months. The leukemia occurrence of
      PLZF-RARalpha/RARalpha-PLZF TM was about 10%, which was similar to PLZF-RARalpha
      TM as that reported before. The latency was over 6 months, not earlier than PLZF
      RARalpha TM only. No morphologic changes of PLZF-RARalpha/RARalpha-PLZF double TM
      blast cells to ATRA were observed, but increased cytoplasmic-nuclear ratio and
      nuclear condensation in bone marrow blast cells were found in combination of ATRA
      with tricostatin A. It is concluded that PLZF-RARalpha/RARalpha-PLZF double
      fusion gene transgenic mice have heterogeneity of pathogenesis. HDAC inhibitors
      such as trichostatin A, in combination with ATRA, induce differentiation of the
      blast/promyelocytic cells from PLZF-RARa/RARa-PLZF double TM, but not ATRA alone.

PMID- 16403253
TI  - Cytobiological and clinicobiological features of AML with 11q23 chromosome
      abnormalities.
AB  - To investigate the interrelationship among morphology, immunology and clinical
      features in adult acute myeloid leukemia cases with 11q23 chromosome
      abnormalities, 210 newly diagnosed AML patients were retrospectively analyzed by
      cell morphology, immunophenotyping, G-banding or R-bamding analysis and clinical
      features. The results showed that 13 cases were found with 11q23 rearrangements
      or deletion (the incidence rate was 6.19%.), totally 84.6% showed the involvement
      with the monocytic lineage. Immunophenotyping tests indicated that AML cases with
      11q23 abnormalities usually expressed the marker molecules of hematopoietic stem
      or progenitor cells, monocytic lineage cells, such as CD34, CD117, CD14, CD15 and
      CD11b. The complete remission rate of the cases with 11q23 abnormalities was
      comparable to that of the cases with normal karyotype (P = 0.075), but the median
      disease-free survival in the former was significantly lower than that in the
      latter (P < 0.001). It is concluded that the category AML with 11q23
      abnormalities accounts for 6.19% of all the newly diagnosed AML cases, that seems
      to be closely associated with monocytic differentiation blocking with a dismal
      prognosis.

PMID- 16403254
TI  - [Purging effects of CD3AK/iNOS in vitro on primary leukemic cells from chronic
      myeloid leukemia patients].
AB  - To investigate the purging effect of CD3AK/iNOS on primary leukemic cells from
      chronic myeloid leukemia patients in vitro, amphotropic packaging cell line PA317
      transfected with the whole length of iNOS gene was cultivated, amplified and
      screened by G418. The viral titer was determined by the NIH3T3 cells. Human
      peripheral blood mononuclear cells were isolated and activated by anti-CD3
      monoclonal antibody in vitro. CD3AK cells were incubated with viral supernatant
      and selected by G418. Resistant clones were assayed for iNOS gene expression by
      RT-RCR. The content of nitric oxide and the activity of iNOS in the culture
      supernatant of CD3AK/iNOS were evaluated by the method of Griess. After BMMNC or
      PBMNC from CML patients were co-cultured with CD3AK/iNOS, CD3AK/Neo and
      CD3AK/iNOS respectively, the expression of bcr/abl fusion gene was detected by
      serial dilution semi-quantitative net RT-PCR assay. The results showed that anti
      G418 positive packaging cell line PA317 transfected with the whole length of iNOS
      gene clones could stably synthesize and excrete recombinant retroviral vectors.
      The titer of recombinant retroviral vectors was 1.0 x 10(5) CFU/ml. After being
      transfected by recombinant retroviral supernatant, the iNOS cDNA was expressed in
      CD3AK/iNOS. The content of NO and activity of iNOS that synthesized and excreted
      by CD3AK/iNOS were notably increased, compared with those of CD3AK. There were
      statistically significant differences in NO content and iNOS activity between two
      groups. After BMMNC or PBMNC from CML patients were co-cultured with CD3AK/iNOS,
      CD3AK/Neo and CD3AK/iNOS respectively, the expression of bcr/abl fusion gene in
      all of them was down-regulated by serial dilution semi-quantitative RT-PCR assay.
      It is concluded that construction of CD3AK/iNOS can markedly increase the content
      of NO and the activity of iNOS, which can be more efficient in in vitro purging
      leukemia cells for autologous hematopoietic stem cell transplantation.

PMID- 16403255
TI  - Comparison between CD19 and CD20 expression patterns on acute leukemic cells.
AB  - In order to provide the evidences for CD19 as a better antibody targeting
      molecule for B lineage acute leukemias than CD20 through the multi-parameter flow
      cytometry analysis of leukemia cells, the samples from 321 patients with acute
      leukemia (AL) were immunophenotyped by multi-color flow cytometry and CD45/SSC
      gating strategy followed by the analysis of CD19 and CD20 expression. The results
      showed that the positive rate of CD19 (115/116, 99.1%) in 116 cases with B
      lineage acute lymphoblastic leukemia (B lineage ALL) was significantly higher
      than that of CD20 (33/116, 28.4%) (P < 0.01); in 17 patients with B
      lineage/Myeloid (B/My) acute mixed lineage leukemia (AMLL), the former positive
      rate (17/17, 100%) was also higher than the latter (5/17, 29.4%) (P < 0.01). Both
      of the two antigens were negative in 29 patients with acute T lymphoblastic
      leukemia and 7 patients with T/My AMLL. The positive rates of CD19 and CD20 in
      152 patients with acute myeloid leukemia (AML) were 7.2% and 2.0%, respectively.
      The difference of the fluorescence intensity between the two antigens on the
      cells from each patient with B lineage ALL or B/My AMLL was statistically
      significant (t = 20.68, P < 0.001). The specificity of CD19 and CD20 in B
      lymphocytic lineage was 92.3% (132/143) and 92.7% (38/41), respectively, while
      the sensitivity was 99.2% (132/133) and 28.6% (38/133), respectively, the former
      sensitivity was significantly higher than the latter (chi(2) = 144.018, P =
      0.001). It is concluded that CD19 continuously and steadily express on almost all
      subtypes of B lineage leukemic cells with homogeneous pattern while only a small
      number of leukemias express CD20. Both the specificity and sensitivity of CD19
      were very high with a much broader reaction pattern than that of CD20 on this
      group of diseases. These indicate that CD19 may be a better antibody targeting
      molecule than CD20 for patients with B-lineage acute leukemia.

PMID- 16403256
TI  - [Abnormal expression of hMSH2 mRNA and mutation P53 protein in acute
      lymphoblastic leukemia].
AB  - In order to investigate the mechanism of acute lymphoblastic leukemic cell
      malignant proliferation, the expressions of hMSH2 mRNA and mutation P53 (mtP53)
      protein in bone marrow cells of de novo acute lymphoblastic leukemia (ALL) were
      determined by in situ hybridization and immunocytochemical methods. The results
      showed the that percentage of positive cell with hMSH2 mRNA expression was (32.88
      +/- 11.46)% in the de novo ALL group and (64.22 +/- 8.51)% in the control group.
      The percentage of positive cell with mtP53 protein expression was (29.25 +/-
      9.45)% in the de novo ALL group, and (12.63 +/- 6.66)% in the control group.
      There was a significant negative correlation between the positive percentages of
      hMSH2 mRNA expression and mtP53 protein expression (r = -0.45, P < 0.05). It is
      concluded that defective MSH2 mRNA expression plays an important role in the
      pathogenesis of acute lymphoblastic leukemia, mtP53 protein mutation plays an
      important role in the development of acute lymphoblastic leukemia, the hMSH2 mRNA
      defect can lead to accumulation of the mutant P53 protein in acute lymphoblastic
      leukemia, and both jointly promote the pathogenesis of ALL.

PMID- 16403257
TI  - [Expression and clinical significance of PTTG and b-FGF in acute leukemia].
AB  - To investigate the expression of pituitary tumor-transforming gene (PTTG) and
      basic fibroblast growth factor (b-FGF) in acute leukemia, as well as the
      relationship of their expression with prognosis in acute leukemia, expressions of
      PTTG and b-FGF in acute leukemia (AL) specimens were detected by
      immunocytochemical technique. The results showed that the expressions of PTTG and
      b-FGF in AL group were higher than that in the control group significantly (P <
      0.01). In AL group, after chemotherapy, the expression of PTTG and b-FGF in de
      novo patients group was higher than in the complete remission patient group
      significantly (P < 0.01). The expressions of PTTG and b-FGF showed positive
      correlation (r = 0.61, P < 0.01). It is concluded that Up-regulation of PTTG and
      b-FGF expression may be involved in the progression of acute leukemia and
      correlated closely with therapeutic effect. Associated detection of PTTG and b
      FGF may help to judge the malignancy degree and prognosis of acute leukemia.

PMID- 16403258
TI  - Comparative study of expressions of cytoplasmic CD79a and other B-lymphoid
      immunomarkers in acute leukemic cells.
AB  - To evaluate the expression of cytoplasmic CD79a (CyCD79a) and other commonly used
      B-lymphoid immunomarkers including cytoplasmic CD22 (CyCD22), CD19, CD20 and CD10
      in various acute leukemia cells and to define the most sensitive and specific
      markers in the diagnosis of precursor B-cell acute lymphoblastic leukemia (pB
      ALL), the immunophenotypic data from 221 de novo adult and pediatric acute
      leukemia patients as studied using multi-parameter flow cytometry in addition to
      routine morphologic and enzyme cytochemical assay, were retrospectively analyzed.
      Cytogenetic and/or molecular biological data in all 45 cases of acute
      promyelocytic leukemia (APL) and 13 cases of acute leukemia suspected as AML with
      the fusion genes such as AML1/ETO and CBFbeta/MYH11 were investigated. The
      results showed that CyCD79a and CyCD22 were the most sensitive and specific
      markers respectively for pB-ALL. Expression of CyCD79a was seen in 100% of 58
      cases of pB-ALL. At the same time, none (0%) of all 147 cases of acute myeloid
      leukemia (AML) and 15 cases of precursor T-cell acute leukemia (pT-ALL) was
      positive for CyCD22. The conclusion is made that united detection of CyCD79a and
      CyCD22 is the optimal immune combination for the diagnosis pB-ALL and the
      distinguishing pB-ALL with AML and pT-ALL.

PMID- 16403259
TI  - [Expression of HoxA10 in acute leukemia and its significance].
AB  - To investigate the expression of HoxA(10) mRNA in acute leukemia patients and its
      significance, HoxA(10) level was detected by reverse transcription polymerase
      chain reaction (RT-PCR) in 50 patients with acute leukemias, 7 healthy volunteers
      and 3 patients with ITP (idiopathic thrombocytopenic purpura). The regularity of
      the expression of HoxA(10) gene in acute leukemia and the relationship between
      HoxA(10) level and the prognosis of leukemia was explored. The results showed
      that HoxA(10) was expressed in all types of acute myelogenous leukemia; HoxA(10)
      message was also observed in acute lymphoblastic leukemia patients and part of
      control groups. 3 normal donors were found not to express HoxA(10). The level of
      HoxA(10) mRNA of acute myelogenous leukemia patients was significantly higher
      than that of acute lymphoblastic leukemia patients and controls (P < 0.01).
      HoxA(10) gene appeared to be more strongly expressed in AML-M(1) and -M(2)
      subtypes than in AML-M(4) and -M(5) subtypes, and the gene was notable high
      expressed in acute promyelocytic leukemia. The number of blast and promyeloid
      cells in the bone marrow was positive related with the level of HoxA (r = 0.635,
      P < 0.01). The level of HoxA(10) of 9 non-responsive patients was higher than
      that of 8 remission patients, but there was no significant difference between
      them (P = 0.258). HoxA(10) was overexpressed in acute myelogenous leukemia. It is
      concluded that HoxA(10) is a major transcription factor regulating hematopoiesis
      and a mark to differentiate lymphoid leukemia and myelogenous leukemia, but not a
      specific gene of cancer. The level of HoxA(10) is related with load of leukemic
      cells and curative effect, and can affect occurrence and development of leukemia
      in combination with many cytokines, HoxA(10) may facilitate the leukemia
      progression with another cofactors.

PMID- 16403260
TI  - [Antineoplastic effect of valproic acid and trichostatin on HL-60 and K562
      cells].
AB  - The objective of this study was to investigate antineoplastic effects of valproic
      acid (VPA) and trichostatin (TSA) on HL-60 and K562 cells in vitro, and the
      synergic effects of VPA or TSA in combination with ATRA. The inhibitory effects
      of VPA, TSA and ATRA in various concentrations and different combinations on
      proliferation of HL-60 and K562 cells were observed by cell growth curves, 50%
      inhibitory concentration (IC(50)), as well as inhibition of leukemia colony
      growth at different time points. The characteristics of cell differentiation or
      apoptosis were analyzed by cytochemical staining, differentiation antigen
      detection, cell cycle assay and A(NBT)/A(MMT) value determination. The results
      showed that HL-60 cell had a lower IC(50) of VPA and TSA compared with K562
      cells. ATRA could significantly enhance the inhibition of VPA, TSA on
      clonegenicity of HL-60 cells and inhibition of VPA on clonegenicity of K562
      cells. HL-60 cells treated with VPA displayed the phenotype of neutrophilic like
      cells, and showed the increases of NBT reduction rate and CD11b expression. No
      evidence for K562 differentiation was found. It is concluded that both VPA and
      TSA inhibit HL-60 cells growth in vitro. VPA induces differentiation of HL-60
      cells to granulocyte. VPA and TSA have a moderate anti-proliferative effect on
      K562 cells. None of these agents induces K562 cell differentiation.

PMID- 16403261
TI  - [Factors regulating expression of antiapoptosis gene survivin].
AB  - To explore the regulation mechanism of survivin gene, the NB4 and HL-60 cells
      were used in experiments, the cell culture in vitro and cell morphological
      observation were performed and survivin mRNA expression was detected by semi
      quantitative RT-PCR. The results showed that the survivin expression in NB4 cell
      was positive. By treatment of 1 micromol/L ATRA, cell differentiation antigen
      CD11b was gradually increased ([chi = 47.002, P = 0.000) and CD33 was gradually
      decreased (chi = 1.614, P = 0.806) with time. Simultaneously, survivin mRNA
      expression was down-regulated and the cell cycle was arrested at G(0)-G(1) phase
      (chi = 58.566, P = 0.000). ATRA could down-regulate the survivin mRNA expression
      of HL-60 cell, but G-CSF, GM-CSF and PHA could up-regulate the survivin
      expression of HL-60 cell. The cytokine could regulate survivin expression in gene
      transcription level. The up-regulation of survivin expression was observed while
      HL-60 cell was stimulated by PHA. The survivin gene expression could be blocked
      by the survivin antisense oligonucleotide. The survivin mRNA expression of NB4
      cell was inhibited by 100 nmol/L-1000 nmol/L survivin antisense oligonucleotide
      in a dose-dependent manner. The survivin mRNA expression in the NB4 cell was
      obviously inhibited in 600 nmol/L survivin AS-ODN groups (38%) while the AS-ODN
      dose increases, the inhibition rate does not descend, but was not inhibited in
      the control groups, liposomes groups and ODN groups. After NB4 cell was treated
      by survivin AS-ODN, the typical morphological changes for the apoptosis emerged
      in NB4 cell. These changes were not found in control groups. It is concluded that
      PHA, GM-CSF and G-CSF can up-regulate the survivin gene expression, but survivin
      AS-ODN and ATRA can down-regulate survivin gene expression. The cell cycle arrest
      at G(0)-G(1) phase while the survivin gene expression was down-regulated by ATRA.
      It suggested that the survivin gene expression is very related to cell cycle. The
      morphological changes of cell apoptosis can be observed when the survivin gene
      expression of NB4 cell was suppressed.

PMID- 16403262
TI  - [Mechanisms of fenretinide-triggered apoptosis in leukemic cells].
AB  - The retinoid N-4-hydroxyphenyl retinamide (4-HPR also known as fenretinide), a
      synthetic derivative of all trans retinoic acid (ATRA), has shown as an efficient
      chemopreventive, chemotherapeutic agent and a potent inducer of apoptosis in
      various cancer cell types in vitro, including leukemic cells. However the
      mechanisms by which 4-HPR has the apoptotic effects is not completely elucidated.
      This study was aimed to investigate the effect of 4-HPR on several leukemic cells
      and explore its mechanisms of effect on U937 cells. The cell growth and
      proliferation experiments were performed [corrected] cell apoptosis was detected
      by annexin V; reactive oxygen species (ROS) and mitochondrial transmembrane
      potential (DeltaPsim) were determined; protein [corrected] expression was
      detected by Western blot. The results showed that 4-HPR inhibited the
      proliferation of U937 cells in a dose- and time-dependent manner. 4-HPR markedly
      [corrected] induced apoptosis in U937 cells, triggered the generation of ROS,
      induced the loss of mitochondrial transmembrane potential, decreased the
      expression of procaspase-8 and procaspase-3. Pretreatment of L-ascorbic acid
      suppressed the generation of ROS, disruption of mitochondrial potential,
      activation of caspases and apoptosis. It is concluded that the generation of ROS
      followed by the disruption of mitochondrial transmembrane potential plays an
      important role on 4-HPR-induced apoptosis in leukemic cells, suggesting that 4
      HPR may be one of mitochondrial-targeted agents with clinical potential in
      treating cancer.

PMID- 16403263
TI  - [Mechanism of lithium chloride-induced proliferation inhibition and apoptosis of
      K562 leukemic cells].
AB  - To investigate the mechanism of proliferation inhibition and apoptosis of K562
      leukemia cells by lithium chloride (LiCl), after K562 cells were treated with
      LiCl (30 mmol/L) cell cycle was examined by flow cytometry (FCM) and the
      expression of bcr/abl fusion gene mRNA was evaluated by RT-PCR. The intracellular
      Li(+) concentrations of K562 cells were determined at different time after
      treated with 30 mmol/L LiCl and the effects of TTX and FSK on intracellular Li(+)
      concentrations of K562 cells were also detected by atomic absorption
      spectrometry. The effects of TTX and FSK on LiCl-induced growth inhibition of
      K562 cells were determined by cell counting in liquid culture. The results showed
      that LiCl (30 mmol/L) caused a sustained arrest in G(2)/M cell cycle and down
      regulated the bcr/abl mRNA expression in K562 cells, the intracellular Li(+)
      concentration of K562 cells increased at 30 minutes after treated with 30 mmol/L
      LiCl and reached apex at 2 hours, thereafter, gradually decreased and balanced at
      4 hours after the treatment. If either Na(+) channel was pre-blocked with TTX or
      K(+) channel was pre-blocked with FSK, the intracellular Li(+) concentrations of
      K562 cells treated with 30 mmol/L LiCl were higher than that in the cells just
      treated with LiCl without pre-blocking. Furthermore, after pre-blocking either
      Na(+) channel with TTX or K(+) channel with FSK, the inhibition rate of K562 cell
      growth by 30 mmol/L LiCl could be increased. It is concluded that the mechanism
      of proliferation inhibition and apoptosis of K562 leukemia cells induced by LiCl
      is probably related with the G(2)/M cell cycle arrest, the bcr/abl mRNA
      expression down-regulation and the status of Na(+), K(+), or Li(+) ion channels
      on K562 leukemia cells.

PMID- 16403264
TI  - [Mechanism of sodium nitroprusside-induced apoptosis in K562 cell line].
AB  - To study the molecular mechanisms of nitric oxide donor sodium nitroprusside
      (SNP) -induced apoptosis in K562 human leukemia cell line, the different
      concentrations of SNP and different time of culture were used to treat K562 cell.
      At the same time, potassium ferricyamide (PFC) was used as control, blank was
      designed in experiment. Cell apoptosis was analysed by cell morphology, DNA
      agarose gel electrophoresis, DNA content, and annexin-V/PI labeling method. The
      TdT-mediated dUTP nick end labeling (TUNEL) assay was used to quantify in situ
      cell apoptosis. Reactive oxygen species (ROS) in cells and mitochondrial
      transmembrane potential (DeltaPsim) were labeled by dihydrorhodamin 123, 2', 7'
      dichlorodihydrofluorescein diacetate and rhodamin 123/PI. bcl-2, bax, bad, p53
      gene proteins and mitochondrial membrane protein were analysed by flow cytometry.
      The results showed that the K562 cell apoptosis was confirmed by typical cell
      morphology, DNA fragment, sub-G(1) phase, TUNEL and annexin-V/PI labeling. A
      majority of K562 cells were arrested in G(0)/G(1) phase. During the process of
      SNP-induced apoptosis in K562 cell, the mean fluorescence intensity of ROS in
      cells was significantly higher than those in blank and PFC control, while the
      DeltaPsim reduced. The expression of p53, bax, bad, Fas protein and mitochondrial
      membrane protein increased and bcl-2 protein decreased after SNP treatment. It is
      concluded that SNP induces K562 cell apoptosis through increasing ROS in cells,
      expressing the p53, bax, bad, Fas protein and mitochondrial membrane protein and
      decreasing bcl-2 protein, opening the mitochondrial permeability transition pore
      and reducing DeltaPsim. Furthermore, the Fas was activated during the apoptosis
      process.

PMID- 16403265
TI  - [Experimental study on apoptosis of leukemia cell line NB4 transfected with WT1
      gene].
AB  - In order to study the potential effects of exogenous WT1 gene isoform on
      apoptosis in leukemia cell line NB4 and its possible molecular mechanisms, the
      eukaryotic expression recombinant vector (pCB6(+)/WTA) containing full-length
      human WT1 isoform (WTA: -17aa/-KTS) cDNA and the vacant vector-alone were
      introduced into the leukemia cell line NB4 respectively by electroporation. The
      WTA mRNA and protein in cells were detected by RT-PCR and Western blot. Binding
      of Annexin V were tested by flow cytometry and agarose gel electrophoresis to
      verify whether exogenous WTA could induce apoptosis of NB4 cells. Expressions of
      p21, p53, bcl-2, bcl-XL and c-myc genes were determined by semi-quantitative RT
      PCR after introducing recombinant vectors into the NB4 cells. The results showed
      that in exposure to As(2)O(3) at 0.8 micromol/L for 48 hours, the NB4/WTA cells
      exhibited the morphological hallmarks of apoptosis, the marked DNA ladder shown
      by gel electrophoresis, and the enhanced apoptosis rate marked by Annexin V. RT
      PCR showed an increase in p21 and c-myc genes expression, a decrease in bcl-2 and
      a relative constant expression of p53, bcl-XL in NB4/WTA cells. It is concluded
      that the introduction and expression of exogenous WTA gene can lead to apoptosis
      of NB4/WTA cells by down-regulating the Bcl-2 gene expression and up-regulating
      the p21 and c-myc genes expression.

PMID- 16403266
TI  - [Effects of RhG-CSF on apoptosis of HL-60 cell induced by cytarabine].
AB  - To investigate the effects of rhG-CSF on apoptosis of HL-60 cell induced by
      cytarabine (Ara-C), HL-60 cell were cultured with Ara-C, with or without rhG-CSF,
      and the changes of HL-60 cells were detected by morphology, including Wright's
      and acridine orange (AO) and ethidium bromide (EB) staining, and MTT assay. The
      results showed that comparing with Ara-C group, the apoptosis level of rhG-CSF +
      Ara-C group was enhanced (P < 0.01), and the OD value of MTT assay declined (P <
      0.01). It is concluded that rhG-CSF can induce the apoptosis of HL-60 cells and
      enhance the apoptosis induced by Ara-C.

PMID- 16403267
TI  - [Using protein chips to study mechanism underlying reversion of drug resistance
      in leukemia cells in tetrandrine alone or in combination with droloxifene].
AB  - The aim of this study was to investigate the mechanism to reverse the drug
      resistance of leukemia cells in tetrandrine (Tet) alone or in combination with
      droloxifen (Drol) by using protein chips and to lay the theoretical basis for the
      clinical applications. Three monoclonal antibodies against P-glycoprotein (P-gp),
      the multidrug resistance-associated protein (MRP1) and the breast cancer
      resistance protein (BCRP) were immobilized onto the agarose gel film-coated glass
      slides. Protein chips were prepared respectively from K562/A02 cells cultured for
      12, 24 and 48 hours with Tet alone or in combination with Drol. The results
      showed that Tet alone or in combination with Drol could decrease only the
      expression of P-gp in a time-dependent manner, the effect for 48 hours as
      follows: Tet + Drol 82.620 +/- 3.227; Tet alone 86.440 +/- 2.906; Drol alone
      87.230 +/- 2.049; control 93.670 +/- 2.748 (P < 0.05). However, down-regulation
      of P-gp by K562/A02 cells cultured with Tet alone or in combination with Drol
      began at 24 hours (Tet + Drol 85.270 +/- 3.095; control 93.670 +/- 2.748, P <
      0.05). The results were coincident with that of FCM. It is concluded that Tet and
      Drol can downregulate the expression of P-gp in the time-dependent way. There is
      a significant difference between Tet alone and Tet combined with Drol at 24 hours
      (P < 0.05). The expression of MRP1 and BCRP are not closely correlated with the
      reversal mechanism of Tet and Drol, and which may be involved in the mechanism of
      this combination to reverse multidrug resistance in leukemia.

PMID- 16403268
TI  - [A preliminary study on mechanisms for resistance of CML patient BM-derived
      bcr/abl+ and Flk1+CD31-CD34- stem cells to STI571 in vitro].
AB  - To evaluate the effect of imatinib mesylate (STI571) on primitive/committed
      malignant progenitor cells in chronic myelogenous leukemia (CML) and to further
      elucidate the mechanisms involved in CML relapse and in some CML cells resistant
      to STI571, bone marrow-derived malignant bcr/abl-positive, Flk1(+)CD31CD34(-)
      cells with hemangioblastic characteristics from CML patients were grown in
      Methocult GF+ media with or without STI571, and inhibitory effect of STI571 on
      proliferation of differentiated and differentiating, bcr/abl(+), Flk1(+)CD31CD34(
      ) cells with hemangioblastic characteristics was investigated in vitro. The
      results showed that in vitro exposure to 5 micromol/L STI571 (the concentration
      of STI571 usually achieved in patients is 1-2 micromol/L) for 96 hours inhibited
      bcr/abl(+) committed progenitors (colony-forming cells, CFCs). No evident
      suppression of normal primitive, bcr/abl(+), and Flk1(+)CD31(-)CD34(-) cells were
      observed. It is concluded that CML primitive stem cells remain viable in the
      presence of STI571 and that inhibition of bcr/abl tyrosine kinase by STI571
      restores normal hematopoiesis by removing the proliferative advantage of CML
      committed progenitors but that elimination of all CML progenitors may not occur.
      So despite dramatic short-term responses in vivo, such in vitro resistance to
      STI571, may translate into disease relapse after prolonged therapy.

PMID- 16403269
TI  - [Reversion of multidrug resistance in HL-60/VCR cells by down-regulation of bcl-2
      with bcl-2 siRNA].
AB  - To evaluate the feasibility of gene therapy using bcl-2 as target in multiple
      drug resistance of leukemia, the small interfering RNA eukaryotic expression
      vector specific to human bcl-2 gene was constructed by gene recombination, then
      transfected into HL-60/VCR cells. Stable transfectants were obtained by G418
      screening. The growth curve and drug sensitivity were detected by using MTT. The
      expression of Bax and ZNRD1 was analyzed by Western blot. The results showed that
      mU6pro-bcl-2 siRNA was successfully constructed and transfected into HL-60/VCR
      cells. The IC(50) of transfected cells to vincristine and adriamycin was
      significantly reduced as compared with that of the control. The expression of
      ZNRD1 in transfected cells was decreased as compared with that of the control,
      while Bax not. It is concluded that the bcl-2 siRNA restores the sensitivity of
      HL-60/VCR cells to conventional chemotherapeutic agents to a certain degree.

PMID- 16403270
TI  - [Establishment of a mouse model for detecting multi-drug resistant minimal
      residual leukemia cells expressing green fluorescent protein].
AB  - This study aimed to investigate the pathophysiology and therapy of multi-drug
      resistant model of minimal residual leukemia in mice. The multi-drug resistant
      model of minimal residual leukemia was established by using P388/VCR-G cell line
      expressing enhanced green fluorescent protein (EGFP) and DBA mice. The results
      showed that P388/VCR-G were inoculated in the abdominal cavities of DBA mice, the
      incidence of leukemia was 100%. Any of these mice with leukemia could not obtain
      remission spontaneously. The model of leukemia was sensitive to cyclophosphamide
      (Cy) and the time of survival was related to the dose of Cy received. The
      logarithm of cells inoculated in mice correlated regressionally with the dose of
      Cy. So this model was ideal for research on minimal residual leukemia. The
      distribution of residual leukemia cells in complete remission was not uniform in
      different organs including liver, spleen, thymus and bone marrow. Minimal
      residual leukemia cells could be found by fluorescent microscopy in freezing
      tissue slice. It is concluded that the multi-drug resistant model of minimal
      residual leukemia expressing EGFP can be established by using P388/VCR-G cell
      line and DBA mice. The minimal residual leukemia cells can be observed by
      fluorescence microscopy in complete remission stage.

PMID- 16403272
TI  - [Significance of CD138/syndecan-1 for multiple myeloma immunophenotypes].
AB  - To establish the method of immunophenotyping testing for patients with multiple
      myeloma (MM), to analyze the characteristics of antigen expression on myeloma
      cells, and to purify primary myeloma cells, CD45/side scatter (SSC) gating tri
      color immunofluorescence (IF) flow cytometry (FCM) was used to test
      immunophenotype of 18 patients with MM, 20 patients with acute leukemia (AL) and
      7 normal controls. Purified primary myeloma cells were obtained by means of anti
      CD138 monoclonal antibody and immunomagnetic microbeads. The results showed that
      myeloma cells displayed a CD45 negative/low positive expression, and SSC was
      located between nucleated red blood cells and neutrophils. Both CD138 and CD38
      were positive while most antigens of T cell, B cell and myeloid cell were
      negative. Positive rate of CD56 was 83.3% and HLA-DR was 44.4% positive. Compared
      with MM patients, CD138 was negative and CD38 was 100% positive in AL patients.
      CD56 was 25% positive. In normal controls, neither CD138 nor CD56 was positive.
      The positive rate of primary myeloma cells after purification was 73%-95% with a
      mean of 86%. It is concluded that CD45/SSC gating procedure is a stable and
      reliable method to detect immunophenotype of MM. CD138 is a correspondingly
      special antigen for myeloma cells. Highly enriched primary myeloma cells can be
      obtained by anti-CD138 antibody and immunomagnetic microbeads.

PMID- 16403271
TI  - [Induction of anti-leukemic immunity of dendritic cells derived from multidrug
      resistant leukemia K562/A02 cells with high expression of P-glycoprotein and
      sensitive K562 cells].
AB  - This study was aimed to investigate and compare the anti-leukemic effect mediated
      by dendritic cells (DC) derived from multidrug resistant (MDR) leukemia K562/A02
      cells with high expression of p-glycoprotein (P-gp) and sensitive K562 cells.
      Multidrug resistant K562/A02 cell line and sensitive K562 cell line from chronic
      myeloid leukemia (CML) were induced for differentiating to DC in complete RPMI
      1640 culture medium supplemented with GM-CSF (1 000 U/ml), IL-4 (500 U/ml) and
      TNF-alpha (100 ng/ml) for 14 days. The morphologic features of DC were observed
      by means of optical microscopy and the phenotype of DC was detected by flow
      cytometry. T-cell stimulating activity was determined by allogeneic lymphocyte
      reaction (allo-MLR). Cytotoxic activity was measured by MTT assay. The results
      indicated that DC derived from K562/A02 cells and K562 cells similarly showed the
      typical morphology of dendritic cell and expressed the surface differentiation
      antigens and costimulatory molecules CD1a, CD83, HLA-DR, CD80 and CD86 of DC. In
      allo-MLR, K562/A02-DC had a higher capacity to induce lymphocyte proliferation,
      compared with K562-DC (P < 0.05). K562/A02-DC and K562-DC could similarly
      generate specific cytotoxic activity against K562/A02 cells or K562 cells
      respectively, but low reactivity against HL-60 cells. More importantly, the
      cytotoxic activity mediated by K562/A02-DC was stronger than that by K562-DC
      against K562/A02 cells or HL-60/VCR cells (P < 0.01, respectively). It is
      concluded that functional DC can be differentiated from multidrug resistant
      leukemia K562/A02 cells as well as sensitive K562 cells in the presence of GM
      CSF, IL-4 and TNF-alpha. Especially, DC derived from K562/A02 cells can induced a
      p-glycoprotein specific anti-leukemic immunity.

PMID- 16403273
TI  - [Inhibition effect of vitamin K2 on human MDS-JSN04 cell line and its possible
      mechanism].
AB  - To study the effects and possible mechanism of Vitamin K(2) (VK(2)) in the
      treatment of MDS-JSN04 cells, the changes of morphologic features of MDS-JSN04
      cells were investigated by cytomorphology, the apoptosis of MDS-JSN04 cells was
      observed by transmission electron microscope; cellular proliferation was
      determined by the MTT assay; cell apoptosis, cell cycle shift and expression of
      myeloid-specific differentiation antigen (CD11b, CD13) were analyzed by flow
      cytometry (FCM). The expression of apoptosis-related genes bcl-2, survivin and
      bax were detected by retrotranscriptase polymerase chain reaction (RT-PCR); the
      activity of caspase-3 was determined by chemiluminescence assay. The results
      showed that the typical apoptotic morphological features appeared in cells
      treated with VK(2) for 72 hours; VK(2) induced apoptosis of MDS-JSN04 cells and
      in a dose-and-time-dependent manner, G(0)/G(1) cell arrest and significantly down
      regulated the expression of bcl-2 and survivin, but had no effect on the
      expression of bax; the activity of caspase-3 significantly increased. It is
      concluded that VK(2) induces apoptosis of MDS-JSN04 cells through activating
      caspase-3 pathways and the apoptosis-related genes bcl-2, survivin may play an
      important role in this process.

PMID- 16403274
TI  - [Effect of recombinant human granulocyte colony-stimulating factor on neutrophil
      morphology, function and phenotype in patients with acute leukemia undergoing
      chemotherapy].
AB  - This study was to explore the effect of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) on neutrophil morphology, function and phenotype in
      patients with acute leukemia undergoing chemotherapy. Neutrophil morphology was
      observed under microscope with oil immersion; phagocytotic function was examined
      by measuring the amount of hydrogen peroxide produced by neutrophil; chemotaxis
      was analyzed by agarose method; oxidative burst was analyzed by flow cytometry
      using immunofluorescence technique; neutrophil phenotype was analyzed by flow
      cytometry and immunofluorescence techniques. The results showed that after rhG
      CSF administration, the increased "toxic" granulation, vacuoles and Dohle bodies
      were observed in neutrophils of patients with acute leukemia. Compared with
      normal control, the functions of phagocytosis, chemotaxis, oxidative burst of
      neutrophil were impaired after chemotherapy, while these functions were enhanced
      and returned to normal level or even to be exceeded after administration of rhG
      CSF. In patients with acute leukemia the neutrophil presented significantly
      higher expression of CD64 and CD62L than that in normal control, and a mild
      increase of CD64 expression and significant increase of CD62L expression were
      found in patients after rhG-CSF treatment. No modifications of CD16, CD32, CD14
      and CD11b expression were detected in these patients before or after G-CSF
      administration. It is concluded that rhG-CSF administration can modify the
      morphology, function and phenotype of neutrophils in the patients with acute
      leukemia undergoing chemotherapy, and these modifications of neutrophil behavior
      may be supposed to be a reason for the enhancement of organism anti-infection
      ability.

PMID- 16403276
TI  - [Effect of GM-CSF on expansion and differentiation of CD34+ megakaryocyte
      progenitor cells from cord blood in vitro].
AB  - To study the effect of GM-CSF on in vitro expansion of megakaryocyte progenitor
      cells from cord blood, CD34(+) cells isolated by magnetic cell sorting system
      (MACS) were cultured in serum-free medium containing TPO, IL-3, SCF and with or
      without various concentrations of GM-CSF (5, 20, 100 ng/ml). The numbers of MNC,
      proportion of CD34(+)CD41(+) cells and CFU-MK were measured at 6, 10 and 14 days.
      The results showed that the expansion of MNC and proportion of CD41(+) cells was
      accelerated distinctly by various concentrations of GM-CSF after 14 days, while
      20 and 100 ng/ml GM-CSF exhibited higher expansion effect than that of 5 ng/ml.
      TPO + IL-3 + SCF with 5 ng/ml or 20 ng/ml GM-CSF could stimulate the formation of
      CFU-MK, while TPO + IL-3 + SCF with 100 ng/ml GM-CSF could inhibit it. It is
      concluded that GM-CSF can accelerate the expansion of megakaryocyte progenitor
      cells from CD34(+) cells in cord blood in the serum-free medium containing TPO +
      IL-3 + SCF.

PMID- 16403275
TI  - [Peripheral stem cell mobilization with medium dose of G-CSF in normal donors].
AB  - The study was aimed to investigate the mobilization effect of medium dose of
      granulocyte colony stimulating factor (G-CSF) in allogeneic peripheral stem cell
      transplantation and changes of T lymphocyte subgroup in PBMNC before and after
      mobilization. G-CSF was administered at 600 microg/d (i.e. 300 microg i.v. twice
      a day) for successive 5 days to 31 matched sibling or unrelated donors for the
      mobilization. Stem cells were harvested on the fourth day. FACS was used to
      analyze the NC, MNC and T lymphocyte subgroups. The results showed that the
      number of NC, MNC, CD34(+) cells and CFU-GM in dose of 600microg/d significantly
      increased (P < 0.05), compared with 300 microg/d; the time for hematological
      reconstruction was significantly shortened (P < 0.05); the ratio of adverse
      effects was not obviously increased (P > 0.05) and the median percentage of
      CD3(+) lymphocytes before mobilization was 46.96% [(32.36-57.45)%], but 40.94%
      [(25.31-48.9)%] after mobilization, while the ratio of CD4(+)/CD8(+) did not
      significantly changed. It is concluded that the administration of G-CSF 600
      microg/d in allo-PBSCT has a good effect in the mobilization of PBSC with minor
      side effects, which can markedly promote hematopoietic reconstitution after
      transplantation. The relative amount of CD3(+) lymphocytes significantly
      decreased and the ratio of CD4(+)/CD8(+) remained unchanged, which may lead to
      alleviation of a GVHD after PBSCT.

PMID- 16403277
TI  - [Influence of hepatocyte growth factor on biological characteristics of bone
      marrow-derived mesenchymal stem cells].
AB  - Hepatocyte growth factor (HGF) is one of major growth factors in the bone marrow
      microenvironments with which the proliferation, differentiation and migration of
      bone marrow-derived mesenchymal stem cells were closely contacted. However, its
      roles in the regulation of proliferation, differentiation and migration of bone
      marrow-derived mesenchymal stem cells remain unclear. This study was aimed to
      investigate the effect of HGF on biological characteristics of bone marrow
      derived mesenchymal stem cells. Expression of c-Met, the receptor for HGF was
      detected by immunohistochemistry assay, cell proliferation was determined by MTT,
      activity of ALP was quantitatively assayed, cell migration and anoikis-induced
      MSC apoptosis were analyzed. The results showed that HGF not influenced the
      proliferation and osteogenic differentiation of bone marrow-derived mesenchymal
      stem cells. Treatment of bone marrow-derived mesenchymal stem cells with
      recombinant human hepatocyte growth factor resulted in inhibition of anoikis
      induced apoptosis. HGF significantly stimulated the migration of bone marrow
      derived mesenchymal stem cells. Both PI-3 kinase and MAPK kinase were proved to
      be involved in HGF-induced migration. It is concluded that HGF/c-Met signal
      regulates the apoptosis and migration of bone marrow-derived mesenchymal stem
      cells.

PMID- 16403278
TI  - [Age-related biological characteristics of human bone marrow mesenchymal stem
      cells from different age donors].
AB  - The aim of this study was to investigate the biological characteristics of human
      bone marrow mesenchymal stem cells from bone marrow of different age donors. The
      experiments were divided into four groups by donors age, group A represented MSC
      derived from fetal bone marrow, group B represented MSC derived from bone marrow
      of 0-20 years old donors, group C represented MSC derived from bone marrow of 20
      40 years old donors and group D represented MSC derived from bone marrow of
      donors older than 40. The growth, purification, proliferation and multipotential
      abilities of MSC in 4 groups were observed and their immunophenotypes were
      determined by flow-cytometry. The level of cytokines (IL-6, SCF, FLT-3L, SDF-1
      and TGF-beta1) were assayed by ELISA method. Cell cycles were analyzed to show
      the proliferation index (PrI). MSCs derived from bone marrow of 4 groups were
      injected subcutaneous into NOD/SCID mouse to observe the safety. The results
      showed that different age donors bone marrow all gave rise to MSC. These cells
      were similar in morphology, antigenic phenotype, differentiation potential and
      cell cycle. The primary culture time of group B was shorter than other groups.
      The duration of passage 1 (P1) was 5.5 days, and the duration of P10 was 33 days,
      after P10 culture, (5.19 +/- 2.15) x 10(10) MSCs were obtained from 8 x 10(6) MNC
      of this group. The primary culture time of groups A, C, D were longer, the
      duration of P1 were 15, 7 and 13 days for group A, C and D respectively, and the
      duration of P10 was 50, 60 and 72 days for group A, C and D, respectively. After
      P10 culture, (4.98 +/- 2.08) x 10(10), (1.86 +/- 0.47) x 10(10), (0.64 +/- 0.22)
      x 10(10) MSCs were obtained from 8 x 10(6) MNC of group A, C and D respectively.
      The morphology of MSC of group A was longer and slender. The ability of expansion
      decreased after P15 for A group, P10 for B group and P8 for C and D groups. The
      levels of SCF, FLT3-L, IL-6 and SDF-1 in group B were higher than other groups.
      Karyotype analysis showed that MSCs from 4 groups were normal, and tumor-like
      tissues were not developed after cultured MSCs were inoculated in NOD/SCID mice.
      It is concluded that there was relationship between age and the biological
      characteristics of human bone marrow mesenchymal stem cells. For clinical use,
      especially in hematopoietic stem cell transplantation (HSCT), 0-20 years old
      donors were perfect MSCs donors who can provide sufficient MSCs in relatively
      short times. MSCs of group B can be used as stem cell source because the
      biological characteristics of MSCs of groups B are superior to that of other
      groups.

PMID- 16403279
TI  - [Induction of immune tolerance for allogenic recipient mice by non-myeloablative
      bone marrow transplantation].
AB  - This study was aimed to explore the effects and mechanisms of transplantation
      tolerance induced by "TBI + cyclophosphamide (CTX)" regimen combined with intra
      bone marrow injection of allogenic BMCs. On day 0 C57BL/6 (H-2(b), B6) mice
      received sublethal dose of total body irradiation (TBI) ((60)Co gamma-ray)
      followed by intrabone marrow-bone marrow transplantation (IBM-BMT) of 3 x 10(7)
      cells/30 microl BMCs from BALB/c (H-2(d)) mice. The recipient mice were given CTX
      intraperitoneally 2 days after IBM-BMT. On day 7 skin grafting was performed and
      the skin survival was observed. The tolerance mechanism was investigated by mixed
      lymphocyte reaction (MLR), IL-2 reverse test, adoptive transfer assay in vitro.
      The results showed that the mean survival time (MST) of skin allografts in group
      treated with TBI + CTX + BMT was significantly longer, compared with that of
      other groups (P < 0.01). On day 90 after IBM-BMT, the phenotypic character of the
      recipient mice (black color) began to convert to that of the donor mice (white
      color). The MLR demonstrated that the immune responses of recipient mice were
      donor-specific tolerance. Suppressive activity in the spleen cells of tolerant B6
      mice was observed in adoptive transfer assay in vitro. IL-2 reversal and the
      phenotypic conversion showed that the tolerance mechanisms were involved in
      clonal anergy and the development of chimerism. It is concluded that the
      nonmyeloablative regimen combined with IBM-BMT can induce a long-term tolerance,
      and the multiple mechanisms including clonal anergy, suppressor cells and
      chimerism were involved in transplantation immune tolerance.

PMID- 16403280
TI  - [RNA isolation from human embryonic tissues].
AB  - To investigate the method of RNA isolation from human embryonic tissues and the
      factors influencing the quality of RNA, the RNA from human embryonic tissues
      obtained with drug-induced labor or non-drug induced labor were isolated by using
      grind with liquid nitrogen or homogenizer without liquid nitrogen. The results
      showed that the positive rates of RNA integrity in grind with liquid nitrogen
      group and in homogenizer without liquid nitrogen group were 68.42% and 29.79%
      respectively, and there was significant difference between these two groups;
      however, there was no statistic difference in positive rate of RNA integrity,
      OD(260)/OD(280) ratio and beta-actin gene expression level between the drug
      induced labor group and non-drug induced labor group. It is concluded that
      pulverize of tissue in liquid nitrogen remains the integrity of RNA isolated and
      may be applied for RNA isolation from human embryonic tissues. The quality of RNA
      is not affected by different methods of induction of maternal labor.

PMID- 16403281
TI  - [Application of real-time quantitative PCR in selection of transfected cell
      strains for transgenic overexpression].
AB  - To explore the feasibility of real-time quantitative PCR (QRT-PCR) for selecting
      cell strains which overexpress a certain transgene, expression level of RbAp46
      was detected in transfected cell strains by using optimal real-time PCR with SYBR
      Green I. Meanwhile, semi-quantitative RT-PCR and Western blot were performed to
      compare with the QRT-PCR. The results showed that values of RbAp46(N) were
      2064.42 +/- 253.47, 860.94 +/- 291.07, 234.456 +/- 31.08, 18.17 +/- 5.14 and 1.46
      +/- 0.54 in K562/RbAp46, K562/CMV, SHG44/RbAp46 monoclone, SHG44/RbAp46
      multiclone and SHG44/CMV, respectively. The results were consistent with that
      determined by semi-quantitative RT-PCR and Western blot. It is concluded that QRT
      PCR provides a highly efficient and reproducible method for selection of
      transfected cell subclones at different level of transgene expression.

PMID- 16403282
TI  - Role of LPS-stimulated human monocyte-derived dendritic cells in the modulation
      of autologous CD4+ CD25+ T Cell activation.
AB  - Dendritic cells (DC) are now recognized as the most potent professional antigen
      presenting cells (APC). Several studies on cancer immunotherapy using different
      approaches to induce cytotoxic T lymphocytes (CTL) in vivo recognizing tumor
      associated antigens have been reported. However, the efficacy of immunotherapy in
      vivo may be limited by the local or systemic suppression of CTL generation or
      function. To explore the ability of lipopolysaccharide (LPS) stimulated human
      monocyte-derived DC involved in activity of autologous CD4(+)CD25(+) T cells, HLA
      A2 restricted p53(264 - 272) peptide was used as tumor antigen, DC generated with
      LPS (DC-LPS(+)) or without LPS (DC-LPS(-)) were co-cultured with autologous T
      cells respectively. The results showed that CD4(+)CD25(+) T cell population in
      the DC-LPS(+) activated T cells was lower than that in the DC-LPS(-) activated T
      cells. This finding suggest that the relationship between DC-LPS(+) and
      population of CD4(+)CD25(+) T cells exists and this property may contribute to
      regulation of T cell responses to tumor-associated antigens.

PMID- 16403283
TI  - [Cytotoxicity of IFN-gamma-activated dendritic cells to freshly isolated acute
      myeloid leukemia cells].
AB  - To investigate the tumoricidal activity of dendritic cell (DC) stimulated by
      interferon-gamma (IFN-gamma) against freshly isolated myeloid leukemia cells and
      its mechanism, the peripheral blood monocytes collected from healthy donors were
      cocultured with interleukin-4 and granulocyte-macrophage colony-stimulating
      factor in medium to induce DC for 7 days. After 12 hour culture in the absence or
      presence of IFN-gamma, the changes of costimulatory molecules were analyzed with
      flow cytometry. To assay the cytotoxicity of DC against freshly isolated acute
      myeloid cells, they were cocultured at various effector-to-target ratio for 18
      hours, then the percentage of tumoricidal activity was measured with (51)Cr
      release assay. To explore the mechanism of DC-mediated cytotoxicity, the change
      of DC surface or intracellular protein expression of Fas ligand (Fas L), TNF
      alpha and TNF related apoptosis-inducing ligand (TRAIL) were analyzed with flow
      cytometry. The results showed that IFN-gamma enhanced cytotoxicity of DC against
      AML cells was (33.8 +/- 1.6)% at E:T as 20:1, compared with unstimulated DC (P <
      0.05); IFN-gamma up-regulated expression of costimulatory molecules of DC surface
      such as CD86 and CD83; after stimulation with IFN-gamma, expression of
      intracellular TRAIL of DC was significantly enhanced, but expression of TRAIL on
      cell surface of DC was low; while the significant changes of Fas L and TNF-alpha
      expression neither on cell surface or in cells were not observed before or after
      stimulation with IFN-gamma. It is concluded that DC stimulated by IFN-gamma
      exhibit tumoricidal activity against AML cells. The cytotoxicity is partially
      related to maturation of DC and TRAIL inducing apoptosis, but not associated with
      death domain-independent mechanism of Fas L and TNF-alpha.

PMID- 16403285
TI  - Morphological study on the megakaryocytes with nuclear extrusion and
      nucleocytoplasmic separation in four cases.
AB  - To investigate the morphological changes of megakaryocytes with nuclear extrusion
      and nucleocytoplasmic separation, the morphological characteristics of
      megakaryocytes in peripheral blood films, bone marrow smears, and bone marrow
      biopsies from 4 newly diagnosed patients with primary myelofibrosis (PMF),
      myelodysplastic syndrome (MDS), myeloblastic leukemia with maturation (M(2)) and
      erythroleukemia (M(6)) were studied by using light microscope. The results showed
      that many kinds of dysmegakaryocytes were observed in bone marrow smears of 4
      cases, while in case A (PMF) and case D (M(6)) micromegakaryocytes were ripped
      apart; in case B (MDS) and case C (M(2)) megakaryocytes were accompanied by
      nuclear extrusion or nucleocytoplasmic separation, and their bodies were large or
      giant, the part of nucleus separated from their body and little cytoplasm
      remained as micromegakaryocytes. The nucleocytoplasmic separation could be
      displayed by immunocytochemistry stain. It is concluded that the phenomenon of
      nuclear extrusion and nucleocytoplasmic separation in megakaryocytes suggested
      the process that dispersed multinuclear releasing towards surround or even
      totally left the cell body during the megakaryocyte maturation. It also showed
      that the micromegakaryocytes may be the result of nucleocytoplasmic separation or
      splittings from multi-separated nucleus.

PMID- 16403284
TI  - Ex vivo expansion of T, NK and CD34+ cells from umbilical cord blood.
AB  - Umbilical cord blood stem cell transplantation (CBSCT) has made significant
      progress in treatment of lethal congenital or malignant disorders. Both the
      incidence and severity of GVHD from CBSCT were lower than that from bone marrow
      and peripheral blood stem cell transplantation, particularly for adult patients,
      but these advantages were also associated with higher rates of relapse. The
      immune-mediated effect of natural killer and cytotoxic T cells against residual
      tumor cells were shown to prevent relapse and to induce remission after bone
      marrow transplantation. To explore possibility of ex vivo expansion of T, NK and
      CD34(+) cells from umbilical cord blood, cord blood was expanded ex vivo with
      different combinations of cytokines, T and NK cells proliferation and
      differentiation were observed. CB MNCs were separated in Ficoll-Isopaque column
      and cultured in IMDM for 14 days with different recombinant cytokines. Cultured
      cells were collected and analyzed for progenitor/stem cell immunophenotyping at
      day 0, 3, 7, and 14 by using flow cytometry. The results indicated that all test
      groups cultured with different combinations of SCF, IL-3, IL-6, IL-7, IL-2 showed
      significant expansion of UCB MNC, compared with the group without cytokines. All
      test groups showed expansion effects on CD34(+) cells, CD34(+) percentage went up
      from 1.6% in fresh CB to the highest 11.9% in group D (SCF + IL-3, IL-6, IL-2).
      The CD34(+) cells peak displayed at day 7 of culture in group A and D, while in
      other two groups B and C appeared at day 14 of culture. The expansion multiple of
      CD34(+) cells in all test groups at day 7 of culture were from 10 to 50. The
      average value of CD3(+) T cell in fresh UCB was 18.7 +/- 4.3%, the CD3(+) T cells
      decreased sharply in the medium without any interleukin, while obvious increase
      were observed in the other test groups containing different combinations of
      cytokines. The maximal expansion multiple of CD3(+) T cells reached 2 times of
      the fresh UCB level. CD56(+) cells amounted to 3.6 +/- 1.9% of fresh UCB, CD56(+)
      cell number increased significantly only in medium containing IL-2. It is
      concluded that T cells, NK cells as well as stem/progenitor cells can be expanded
      in the same time from CB-MNC with the combinations of cytokines.

PMID- 16403286
TI  - [Inherited afibrinogenemia caused by compound heterozygous mutations in the beta
      beta-chain of fibrinogen].
AB  - Congenital afibrinogenemia is a rare autosomal recessive disorder, characterized
      by the complete absence or extremely reduced level of fibrinogen. To analyze the
      phenotype and genotype of a family with inherited afibrinogenemia, laboratory
      studies including activated partial thromboplastin time (APTT), prothrombin time
      (PT) and thrombin time (TT) were tested in the proband and 9 family members.
      Fibrinogen (Fg) in plasma were measured by both functional and immunoturbidimetry
      assay. All the exons, exon-intron boundaries and promoter regions of three Fg
      genes were analyzed by direct sequencing. 102 healthy blood donors were used as
      normal control. The results showed that phenotype of the proband was diagnosed as
      afibrinogenemia. Compound heterozygous mutations in Fg FGB gene were detected in
      the proband. One was a nonsense mutation (Arg17stop) in exon 2, traced back to
      the proband's mother. The other was a missense mutation (Gly347Arg) in exon 7,
      which was from the proband' s father. It is concluded that afibrinogenemia is
      caused by the compound heterozygous mutations Arg17stop and Gly347Arg in the Beta
      beta-chain of fibrinogen.

PMID- 16403287
TI  - [A2 domain of human von Willebrand factor expressed in E. coli and its biological
      activity].
AB  - Von Willebrand factor (vWF) is the unique substrate for the metalloprotease,
      ADAMTS-13, and plays a pivotal role in the pathology of von Willebrand disease
      (vWD) and thrombotic thrombocytopenic purpure (TTP). To study the pathogenesis of
      TTP and to establish a method to diagnose TTP, the DNA fragment of vWF-A2 domain
      was amplified and inserted into expression vector with 6 x His tag (pQE-30), the
      recombinant expression vector was transformed into E. coli (strain M15) and
      induced by IPTG. The recombinant fragment comprising residues 718-905 of mature
      vWF was designated as rvWF-A2. It was purified by Ni-NTA resin column
      chromatography and refolded in Tris buffer containing GSH and GSSG. The results
      demonstrated that rvWF-A2 was expressed successfully in E. coli M15, amounting to
      42% of total bacterial protein with the purity over 98%. It was identified that
      rvWF-A2 can be efficiently cleaved by the citrated normal plasma while no
      cleavage can be detected by the TTP plasma or plasma with EDTA. It is concluded
      that rvWF-A2 expressed efficiently in E. coli demonstrated excellent biological
      activity, which lays a solid foundation for establishment of method to measure
      quantatively the activity of ADAMTS-13.

PMID- 16403288
TI  - [Inhibiting effect of adenosine on platelet activation in vitro].
AB  - This study was aimed to investigate the inhibiting effects of adenosine on
      platelet in vitro in order to select functional protectants for platelets before
      lyophilization. Platelet membrane surface CD62P expression was assayed by flow
      cytometer (FCM). Platelet aggregations induced by restocetin, thrombin, ADP and
      propyl gallate were detected by APACT-2. The results showed that platelets
      membrane surface CD62P expression increased significantly after pre-treating of
      freeze-drying. 0.75 mmol/L adenosine could inhibit CD62P expression in a dose
      dependent manner. Adenosine could inhibit platelet aggregation induced by propyl
      gallate, but no action on restocetin. When adenosine concentration was 1.0 mmol/L
      or higher, the aggregation induced by thrombin was significantly restrained. When
      concentration of adenosine was 0.75 mmol/L, platelet activation resulted from
      retreating could be inhibited and platelet aggregation induced by restocetin and
      thrombin were not affected markedly. It is concluded that adenosine can be one of
      the functional protectants and activation inhibitors in vitro for platelet cryo
      preservation.

PMID- 16403289
TI  - [Application of cationic propyl gallate as inducer of thrombocyte aggregation for
      evaluating the platelet function of platelet donors].
AB  - The purpose of study was to investigate the feasibility of the application of
      cationic propyl gallate (C-PG) as inducer of platelet aggregation for evaluating
      the platelet function of single-donor plateletpheresis and identifying the
      incidence of defective platelet function among donors. Experiments were as
      follows: 3 healthy volunteers' platelet aggregation induced by 100-300 micromol/L
      C-PG was determined by LG-PABER analyzer to observe the effect of C-PG
      concentration on platelet aggregation; 30 healthy volunteers' platelet
      aggregation before and 24 hours after administration of 200-400 mg
      acetylsalicylic acid (ASA) was examined after induction by 200 micromol/L C-PG
      for determining the cut-off value to discriminate platelet dysfunction donors;
      the platelet aggregation of 483 platelet donors was detected and the activated
      plasma clotting time (APCT) of donors who have deficiency in platelet aggregation
      was examined for investigating the incidence of defective platelet function among
      donors. The results showed that platelets were activated by C-PG induction in a
      dose dependent manner, when concentration of C-PG reached 200 micromol/L, the
      percentage of platelet aggregation was highest. It significantly decreased after
      24 hours with ASA than that before the administration (P < 0.001), especially in
      180 seconds induced by C-PG. If cut-off point was fixed on the platelet
      aggregation < 20% in 180 seconds, donors of platelet dysfunction can be selected
      effectively. 25 of defective platelet aggregation function among 483 donors were
      detected, and 11 out of 25 platelet dysfunction donors had the deficiency in
      procoagulant activity with prolonged APCT. It is concluded that C-PG as inducer
      of platelet aggregation is feasible to screen the platelet function of donors.
      Five percent of platelet donors has function defect examined by C-PG as inducer
      of platelet aggregation.

PMID- 16403291
TI  - [Effect of vitamin C antioxidative protection on human red blood cells].
AB  - In order to investigate the effect of antioxidants on human blood, vitamin C was
      selected and added into plastic blood storage bags with CPD, and stored at 25
      degrees C. During 6 days of storage, some indexes as ATP, SOD, MDA, K(+)
      concentration and superoxide radicals were detected and were compared with
      control group, The results showed that ATP and SOD activity in whole blood with
      vitamin C during 6 days of storage was higher then that in control group (P <
      0.05, P < 0.01), the MDA and plasma K(+) concentrations in stored whole blood
      with vitamin C during 6 days of storage were lower than that in control group (P
      < 0.05, P < 0.01), the superoxide radical concentrations in stored whole blood
      with vitamin C decreased lower than that in control group (30%). The conclusion
      was made that vitamin C increases activities of ATP and SOD, decreases
      concentrations of MDA, plasma K(+) and superoxide radicals during blood
      preservation.

PMID- 16403290
TI  - [A method for Rhesus box test].
AB  - To study the method for Rhesus box test and its significance, the sequence
      specific primers of upstream, downstream and hybrid Rhesus boxes were designed
      according to RhD gene sequence; the upstream, downstream and hybrid Rhesus boxes
      were determined by PCP-SSP and mismatched PCR. The results showed that this
      method was confirmed by DNA Standard test. It was shown that in unrelative RhD
      positive individuals RHD(+)/RHD(-), RHD(+)/RHD(+) genotype accounted for 9.00%,
      91.00% respectively, and in RhD negative individuals RHD(+)/RHD(-),
      RHD(+)/RHD(+), RHD(-)/RHD(-) genotype were 26.14%, 3.92%, 69.94% respectively. It
      is concluded that the method of Rhesus box test was confirmed to be reliable and
      can be used for the identification of RhD haplotype gene structure, as well as
      for study on inheritance, clinical transfusion and neonatal hemolytic diseases.

PMID- 16403292
TI  - [Polymorphism of killer cell immunoglobulin-like receptors gene family in
      Zhejiang Han population].
AB  - To analyze killer immunoglobulin (Ig)-like receptor (KIR) gene content and
      allelic polymorphism in Zhejiang Han population, samples were genotyped by
      polymerase chain reaction sequence-specific primers (PCR-SSP). The results
      demonstrated that all 17 KIR genes could be observed in the population. All
      individuals contained 2DL4, 3DL2 and 3DL3 genes. The frequencies of these genes
      was 1.00. 2DL1, 2DL3, 2DP1, 3DP1*003, 3DL1, 2DS4*001/002 loci were more common,
      their frequencies were 0.902, 0.902, 0.902, 0.902, 0.7598, 0.5615 respectively,
      while the frequencies of 2DL2, 2DL5A, 2DL5B, 2DS1, 2DS2, 2DS3, 2DS4*003, 2DS5,
      3DS1 and 3DP1*001/002 were relatively lower. The A KIR haplotype was the most
      prevalent (74.7%) in Zhejiang Han population and there were 12 different KIR
      haplotypes in total, the most common was 2 (53.0%). Twenty six different
      genotypes have been found in the population, AJ (2, 2) and AF (1, 2) showed
      higher frequencies, followed by AH (2, 5), NN2 (2, 6), AI (1, 5) and AG (1, 1).
      Fifteen of these genotypes have not been found in Caucasians so far and four new
      KIR profiles could not be assigned to the haplotypes according to standard assign
      method. In conclusion, there are distinctive frequencies of KIR gene content,
      haplotype as well as genotype in Zhejiang Han population.

PMID- 16403293
TI  - [Evaluation of the effects of glycosylation on in vivo survival of cold-storage
      human platelets by using rabbit model].
AB  - To study the effects of glycosylation on survival of cold-storage human platelets
      by using rabbit model. (51)Cr-labeling platelets were used to detect the platelet
      storage survival. The human platelets (2.0 x 10(12)/L) treated with 5 g/L uridine
      diphosphate galactose (UDP-Gal) were stored in 4 degrees C refrigeratory up to 10
      days. The survival of human platelets in rabbits whose reticuloendothelial system
      was inhibited by the administration of ethyl palmitate was monitored in blood
      drawn at various times after the platelet transfusion. The results showed that
      the survival rate of platelets was significantly increased in cold-storage human
      platelets by UDP-Gal treatment. The survival rates of platelets at 2 hours after
      transfusion into rabbits in groups of fresh platelets group, UDP-Gal + cold
      platelets group and cold platelets group were (68.9 +/- 8.5)%, (65.4 +/- 8.0)%
      and (5.0 +/- 2.6)%, respectively. Compared with cold platelets group, significant
      differences were seen among all groups (P < 0.01). UDP-Gal + cold platelets group
      had no significant differences compared with fresh platelets group (P > 0.05). It
      is concluded that UDG-Gal can provide the protective effect on cold-storage human
      platelets and prolong the survival time of refrigerated human platelets in rabbit
      model.

PMID- 16403294
TI  - [Determination of ABO blood group genotypes with one tube PCR reaction].
AB  - This study was aimed to establish one tube PCR reaction technique to determine
      ABO blood group genotypes. Salting-out method was adopted to extract genomic DNA;
      one tube polymerase chain reaction with GeneScan technique was used to identify
      ABO genotypes. The results showed that the ABO genotypes of 132 samples were in
      accordance with the phenotypes determined by serological technique. The
      frequencies of A, B and O were 0.205, 0.159 and 0.636 respectively. AA, AO, AB,
      BB, BO and OO genotypes were 8 (6.1%), 31 (23.5%), 7 (5.3%), 6 (4.5%), 23
      (17.4%), and 57 (43.2%) respectively. It is concluded that one tube polymerase
      chain reaction with GeneScan technique can determine the genotypes of ABO blood
      group.

PMID- 16403295
TI  - [Study on the molecular genetics basis for one para-Bombay phenotype].
AB  - To investigate the molecular genetics basis for one para-Bombay phenotype, the
      red blood cell phenotype of the proband was characterized by standard serological
      techniques. Exon 6 and 7 of ABO gene, the entire coding region of FUT1 gene and
      FUT2 gene were amplified by polymerase chain reaction from genomic DNA of the
      proband respectively. The PCR products were purified by agarose gels and directly
      sequenced. The PCR-SSP and genescan were performed to confirm the mutations
      detected by sequencing. The results showed that the proband ABO genotype was
      A(102)A(102). Two heterozygous mutations of FUT1 gene, an A to G transition at
      position 682 and AG deletion at position 547-552 were detected in the proband.
      A682G could cause transition of Met-->Val at amino acid position 228, AG deletion
      at position 547-552 caused a reading frame shift and a premature stop codon. The
      FUT2 genotype was heterozygous for a functional allele Se(357) and a weakly
      functional allele Se(357), 385 (T/T homozygous at position 357 and A/T
      heterozygous at 385 position). It is concluded that the compound heterozygous
      mutation--a novel A682G missense mutation and a 547-552 del AG is the molecular
      mechanism of this para-Bombay phenotype.

PMID- 16403296
TI  - [Pulmonary fungal infection in malignant hematological diseases: an analysis of
      14 cases].
AB  - The objective of this study was to evaluate the etiological factors, diagnosis
      and therapy of pulmonary fungal infection in hematological malignancies, 14 cases
      of malignant hematological disease with pulmonary fungal infection were collected
      and analyzed. The results showed that 11 out of 14 cases had the respiratory
      manifestations, sputum was sticky and difficult to be expectorated in 7 cases, X
      rays in chests showed shadows with features of stigma and sheet in 11 cases,
      Candida albicans and aspergillus infection were observed in 10 and 2 cases
      respectively, the numbers of neutrophil were below 0.5 x 10(9)/L in 8 cases and
      below 1.0 x 10(9)/L in 3 cases respectively, fluconazole was used for 12 cases
      and clinical symptoms of 11 cases were improved within two weeks. In conclusion,
      the occurrence of pulmonary fungal infection in malignant hematological diseases
      is associated with intensive chemotherapy, decrease of neutrophil counts and
      using of broad-spectrum antibiotics, the diagnosis at early stage is difficult
      and clinicians should pay more attention to its clinical and laboratory
      examinations, and give them therapy in time.

PMID- 16403297
TI  - [Neurological complications following haploidentical bone marrow
      transplantation].
AB  - To explore the occurrence patterns of neurological complications following
      haploidentical bone marrow transplantation, a series of clinical data as the
      onset time, etiology, choices of therapies and prognosis in 10 patients with
      neurological disorders were summarized. The results showed that complications
      occurred in 10 out of 74 patients after bone marrow transplantation, which
      include 3 with encephalorrhagia, 3 infection, 1 epilepsy, 1 Guillian-Barr's
      syndrome, 1 encephalopathy and 1 schizophrenia. 4 patients died of neurological
      complications. IN CONCLUSION: neurological complications commonly occurred in
      haploidentical bone marrow transplantation, and encephalorrhagia might be the
      main indication that needs intensive care. Moreover, central nerve system
      infection and peripheral nerve diseases associated with slow immune
      reconstitution should have clinical interests.

PMID- 16403298
TI  - [Detection of MRD and its clinical application--review].
AB  - With recent development and progress achieved in the diagnosis and treatment of
      leukemia, relapse of disease still remains as the major problem in clinical
      management and the minimal residual disease (MRD) has been confirmed to be
      associated with leukemia relapse in the past decades. Due to the low sensitivity,
      morphology-based assays have limitation in the MRD monitoring. With the
      development of molecular assays, especially the real-time RT-PCR method have been
      a sensitive, precise and reliable tool to MRD detection. Numerous clinical
      studies demonstrated that the existence of MRD reflects the clinical and
      molecular response, and remain as a major prognostic factor for leukemia. Another
      important application of MRD detection is to evaluate the efficacy of different
      therapy at molecular level. In this paper, the different methods and their
      clinical application for MRD detection were systemically reviewed and it is
      confident that the establishment of standardized MRD detection system will be
      important in the clinical prevention for relapse of leukemia.

PMID- 16403299
TI  - [Mechanism of CD4+CD25+ and CD8+ regulatory T cells--review].
AB  - Regulatory T cells (Treg) play a key role in the negative regulation of the
      immune system, which can inhibit inappropriate self-reactive T cells, as well as
      limit the range, extent and lasting time of immune responses, so as to inhibit
      the proliferation of CD4(+) and CD8(+) effector T cells. In view of these
      properties, there is little doubt about the enormous potential value of Tregs in
      molecular mechanisms and clinical treatment of human autoimmune disorders, graft
      versus-host disease (GVHD) and allergies. In this review, the molecular
      mechanisms of CD4(+)CD25(+) Treg and CD8(+) Treg were mainly discussed, and
      challenge with which study on Treg cells is faced and prospects were briefly
      described.

PMID- 16403300
TI  - [RNA interference (RNAi) as novel approach for gene silencing--review].
AB  - RNA interference (RNAi), a highly conserved evolutionary process of post
      transcriptional gene silencing, can be triggered by small interfering RNAs
      (siRNAs) that mediate sequence-specific mRNA degradation. The article summarized
      some aspects of the mechanism of RNAi, siRNA design and delivery of siRNAs to
      mammalian somatic cells. And some hurdles in practice were also discussed.

PMID- 16403303
TI  - [In Process Citation]

PMID- 16403301
TI  - [Interregulation of VEGF/R endostatin and MMP in the angiogenesis of hematologic
      malignancies--review].
AB  - Some kinds of angiogenic correlation factors, e.g. VEGF/R, MMP, endo statin, are
      relative to the process of hematologic malignancies. The mechanisms of adjusting
      themselves and controlling mutually have been hot points of the academic research
      in last few years. Although the rapid progress has been made in studies of this
      field, it is still hard to come into a systematic theory now. This article
      introduces the last progress in the field of positive and negative regulatory
      factors of VEGF/R system in the angiogenesis of hematologic malignancies, the
      regulation of MMP and its relation with VEGF/R, the regulation of ES and its
      relation with VEGF/R and MMP.

PMID- 16403302
TI  - [Progress of studies on multidrug resistance in hematological malignancies-
      review].
AB  - Chemotherapy remains a major route of intervention in hematological malignancies.
      However, a key issue in the treatment of hematological malignancies is the
      development of multidrug resistance (MDR) to chemotherapeutic drugs. Several
      mechanisms may account for this phenomenon, including biochemical mechanisms,
      such as the overexpression of resistance-conferring proteins and physiological
      mechanisms involving the hematopoietic microenvironment. In this article the
      pathomechanism, diagnostic approach, interpretation of results from clinical
      samples and correlations with hemopoietic microenvironment were briefly reviewed.
      The aspects of development and problems in MDR study as well as detection methods
      for MDR were also discussed.

PMID- 16403304
TI  - [In Process Citation]

PMID- 16403305
TI  - [In Process Citation]

PMID- 16403306
TI  - [In Process Citation]

PMID- 16403307
TI  - [In Process Citation]

PMID- 16403310
TI  - [In Process Citation]

PMID- 16403309
TI  - [In Process Citation]

PMID- 16403308
TI  - [In Process Citation]

PMID- 16403311
TI  - [In Process Citation]

PMID- 16403312
TI  - [In Process Citation]

PMID- 16403313
TI  - [In Process Citation]

PMID- 16403314
TI  - [In Process Citation]

PMID- 16403315
TI  - [In Process Citation]

PMID- 16403316
TI  - [In Process Citation]

PMID- 16403317
TI  - [In Process Citation]

PMID- 16403318
TI  - [In Process Citation]

PMID- 16403319
TI  - [In Process Citation]

PMID- 16403320
TI  - [In Process Citation]

PMID- 16403321
TI  - [In Process Citation]

PMID- 16403322
TI  - [In Process Citation]

PMID- 16403324
TI  - [In Process Citation]

PMID- 16403323
TI  - [In Process Citation]

PMID- 16403326
TI  - [In Process Citation]

PMID- 16403325
TI  - [In Process Citation]

PMID- 16403328
TI  - [In Process Citation]

PMID- 16403327
TI  - [In Process Citation]

PMID- 16403329
TI  - [In Process Citation]

PMID- 16403332
TI  - [The way from the fat food].

PMID- 16403333
TI  - [The obesity epidemic in Denmark].
AB  - In the last 25-30 years, there has been a marked increase in the prevalence of
      obesity within almost all age groups of the Danish population. The largest
      increase has been documented in studies based on objective data from total
      populations, and the latest data show the increase as continuing. The Danish
      studies show heterogeneity in the development of the obesity epidemic within
      various birth cohorts over time. This indicates a need for further etiological
      research, not only into behavioural factors but also into early life factors that
      may explain some of this pattern.

PMID- 16403334
TI  - [Obesity in Denmark--why has it not gone so badly?].
AB  - In the Western world the number of obese people is increasing, but in Denmark the
      incidence is not on the same scale as in the USA. Although several factors may be
      of importance, Danes are more physically active and their intake of beverages
      with added sugar is less than in the American population.

PMID- 16403335
TI  - [Alternative causes of obesity].
AB  - The prevailing understanding of the causes of obesity is based on the disturbance
      of the thermodynamic law of energy balance, primarily through increased intake or
      decreased expenditure of energy. Alternative causes of obesity, which still
      respect the law but also allow for primary fat accumulation, are: virus infection
      of fat cells, energy supply from bacterial fermentation of indigestible food
      components, psychosocial factors mediated by psychoneuroendocrine pathways,
      sleeplessness or poor quality of sleep and early life programming, in addition to
      the well-known and proven genetic programming.

PMID- 16403336
TI  - [Fitness, physical activity and death from all causes].
AB  - Obesity and physical inactivity are both associated with illness and death. A
      review of the literature has shown that the objectively measured level of fitness
      and self-reported physical activity both have a prognostic relationship with
      death from all causes, independently of BMI. Furthermore, there is evidence for a
      dose-response effect of physical activity. It is concluded that regular physical
      activity has health-beneficial effects which are beyond its effect on weight
      control.

PMID- 16403337
TI  - [The importance of physical activity and fitness in avoiding the complications of
      obesity].
AB  - We have reviewed whether the complications of obesity can be attributed to low
      levels of physical activity and fitness, or if fatness per se has adverse effects
      on health. In both observational and interventional studies, fatness and
      inactivity seem to be independent risk factors. Abdominal obesity is a predictor
      of cardiovascular disease, which is independent of low fitness level, and obesity
      affects other risk factors adversely than inactivity does. However, physical
      activity does reduce the risk of type 2 diabetes and heart disease. It is
      concluded that both inactivity and obesity have an adverse effect on health.

PMID- 16403338
TI  - [The genetics of obesity].
AB  - Although environmental factors clearly play a role, studies of twins and adoptees
      show that obesity is a familial trait which to a large degree can be ascribed to
      genetic factors. According to evolutionary models, obesity-causing variants may
      originally have had an evolutionary benefit, whereas in a modern environment they
      pose a risk. Despite a clear genetic cause, the molecular genetic variations
      underlying common forms of obesity are not clear. Out of many hundred candidates,
      only a few hold up, and only variations in the MC4R gene have been found with a
      prevalence which may lead to common forms of obesity.

PMID- 16403339
TI  - [Molecular pathogenesis in monogenic and polygenic obesity].
AB  - During the last few years, studies of the molecular pathogenesis of obesity both
      in mouse models and in the rare cases of monogenic obesity in humans have added
      significantly to our understanding of the key role of the hypothalamus in
      mediating hunger and satiety. These insights have brought us closer to the
      development of rational therapies of obesity, the epidemic of which is continuing
      in the post-industrial society, which is characterised by sedentary behaviour
      patterns.

PMID- 16403340
TI  - [Prevention of obesity].
AB  - Obesity increases the risk of lifestyle diseases, poor quality of life,
      hospitalisation and shortening of life. Globally, obesity is on the rise, and as
      the current treatment options have generally been disappointing, many people
      argue that primary prevention is preferable. However, as yet documentation of
      effective primary prevention is lacking, and results indicate that one-sided
      intervention is ineffective. Despite the lack of documentation, many initiatives
      are being undertaken, both nationally and internationally, and it is recommended
      that Denmark also initiate a collaborative official effort.

PMID- 16403341
TI  - [Why is weight loss so often followed by weight regain? Basal biological response
      as a possible explanation].
AB  - In general, treatment of obesity results in only relatively moderate weight loss
      (5-10%). Another major problem is long-term weight loss maintenance. The reason
      for the weight regain after weight loss is related to both psychological and
      basal physiological mechanisms. In this review we summarise the research from
      both animal and human studies showing that there are powerful physiological
      reactions that can be detected in association with weight loss. Weight loss seems
      to result in a pronounced stimulation of the appetite and a long-lasting fall in
      both the basal and exercise-induced metabolic rates. These energy-conserving
      mechanisms may partially explain the difficulty in maintaining weight loss.

PMID- 16403342
TI  - [Drug treatment of obesity].
AB  - Acceptable adverse effects and a clinical relevant weight loss of 3 to 5
      kilograms have been found in long-term randomized clinical trials for sibutramine
      (Reductil) and orlistat (Xenical); these drugs may be prescribed for treatment of
      obesity for a duration of one and four years, respectively. This also seems to be
      the case for rimonabant (Acomplia), which is expected to receive approval in 2005
      or 2006. However, until data on morbidity and mortality are available from RCTs,
      there is no absolute indication for prescribing drugs for treatment of obesity.

PMID- 16403343
TI  - [Lifestyle intervention in the treatment of severe obesity].
AB  - INTRODUCTION: The prevalence of overweight and obesity is escalating globally,
      and in Denmark more than 10% of the population are now severely overweight. The
      aim of this study was to estimate the short-term health effects of 15 weeks of
      intensive lifestyle intervention composed of physical activity, dietary changes
      and personal development in severely obese subjects of both sexes. MATERIALS AND
      METHODS: The 27 subjects were weighed weekly. Fat percentage, abdominal
      circumference, maximum oxygen uptake, heart rate, oral glucose tolerance and
      blood lipids were measured at baseline and in week 15. The intensive lifestyle
      intervention was completed under supervision at a stay at Ebeltoft Kurcenter, and
      the goal was a weight loss of approximately 1% per week. RESULTS: At baseline,
      the participants' average body mass index (BMI: kg/m2) was 44 +- 1; the BMI was
      reduced by 11% after the stay (p<0.001). Body weight was reduced by 14 +- 4 kg
      (p<0.001), corresponding to 76% of the desired weight loss. The subjects' fat
      mass was reduced by 4% (p<0.001), and their maximal oxygen uptake was enhanced by
      25% (p<0.001). Concerning the blood lipids, total cholesterol was reduced by 8%
      (p = 0.03); there was no significant change in LDL level and a reduction of 15%
      (p<0.05) in HDL level. After the intervention, oral glucose tolerance was
      significantly improved (p<0.001). CONCLUSION: After 15 weeks of intensive
      lifestyle intervention, there were significant improvements in aerobic fitness
      and metabolic risk parameters, and the observed weight loss was equivalent to
      that obtained by surgical treatment. Decisive in the choice of obesity treatment
      will continue to be the extent of success in permanent weight loss.

PMID- 16403344
TI  - [Prevention and treatment of obesity in children].
AB  - In the last 10 years, there has been a marked increase in the prevalence of
      obesity in children beginning at 3-4 years of age. The only realistic solution to
      the problem is prevention. Although there is limited evidence for the
      effectiveness of preventive programmes, there is a consensus that multisectorial
      action is urgently needed. This should include intervention at the family,
      school, municipal, regional and national levels, including the commercial sector
      and food companies. Treating childhood obesity has not been very successful, but
      some comprehensive community-based treatment programmes have shown reasonable
      long-term results. There is a need to establish such community-based treatments
      with emphasis on psychological aspects.

PMID- 16403345
TI  - [Weight loss treatment of obese type 2 diabetic patients].
AB  - Weight loss of several kilograms improves glycaemic control and the lipid profile
      and reduces blood pressure. A consultation with a clinical dietician who is
      educated in behaviour therapy can, for many patients, induce a weight loss of 5
      10%. The use of orlistat and sibutramine has been shown to increase weight loss
      by about 2-6 kilograms. A very-low-calorie diet (VLCD) promotes faster and
      greater weight loss. Surgical treatment of obesity results in considerable weight
      loss and often normalisation of blood glucose levels. Except for surgically
      treated patients, most patients begin to regain the weight lost four to six
      months after the start of the change in diet.

PMID- 16403346
TI  - [Guidelines for treatment of overweight/obesity, 2006].
AB  - Guidelines for evaluation and treatment of overweight and obesity in adults in
      Denmark are given. These guidelines are evidence-based and are similar to
      international guidelines.

PMID- 16403347
TI  - [Metabolic consequences of overeating].
AB  - A sedentary lifestyle, in conjunction with excessive food intake, is contributing
      to the worldwide increasing prevalence of obesity. Overeating is associated with
      insulin resistance, hypertension, dyslipoproteinaemia and endothelial
      dysfunction. A complicated network of cellular mechanisms has recently been
      suggested to play a central role in the control of energy homeostasis and
      metabolic response to overfeeding in animals. Understanding these mechanisms will
      substantially increase our knowledge about the physiological and biochemical
      factors leading to obesity and insulin resistance in humans.

PMID- 16403348
TI  - [Osteoarthritis and obesity].
AB  - Epidemiological studies show an increased prevalence of osteoarthritis of the
      knee and hand with increased body mass index [BMI]. Osteoarthritis of the hip
      joint is not related to BMI. The connection between obesity and osteoarthritis
      cannot exclusively be explained by genetic factors or by the accumulation of tear
      and wear. Overweight occurs prior to knee joint degeneration, not as a result of
      diminished activity due to joint degeneration. Weight control seems to be an
      influential tool in the prophylaxis of overweight-specific joint degeneration.

PMID- 16403349
TI  - [Osteoarthritis and obesity. Prognosis and treatment possibilities].
AB  - Increases in both overweight and life expectancy of the population will lead to a
      larger number of patients with knee problems due to osteoarthritis (OA). Several
      changes, metabolic as well as functional, link obesity with OA. Randomised
      controlled trials have shown substantial and clinically relevant disability and
      symptom relief in obese patients with knee OA following moderate weight loss.
      While exercises are good for the functional status in general, it is advisable
      initially to prescribe weight loss as therapy of patients with a combination of
      obesity and OA.

PMID- 16403350
TI  - [Psychological aspects of obesity].
AB  - Although knowledge of the biological aspects of obesity is increasing very
      rapidly, psychological approaches are increasingly in demand. Psychological
      theory and research concerning the emotional and cognitive impacts of being
      obese, the psychological causes involved in obesity, and the psychological
      elements of treatment and motivations for treatment are requested. There is no
      clear separation between the psychological factors that function as causes of
      obesity and the psychological effects of obesity. Rather, they appear to be
      related in a circle of interconnectedness. This is important to keep in mind when
      seeking ways to motivate and support obese patients.

PMID- 16403351
TI  - [Obesity and health economics. Review and status].
AB  - Cost-of-illness analyses are concerned with the societal economic impact of
      obesity such as treatment-costs and lost production related to morbidity and
      mortality. As regards allocation of resources a growing number of cost
      effectiveness analyses of different interventions have appeared. In addition
      several economic analyses look at how obesity affects wage level and how the use
      of price-subsidies affects the consumption of products and services. Most
      recently health economic analyses of possible explanations of the rise in the
      prevalence of obesity have emerged.

PMID- 16403358
TI  - [Peroral antithrombotic treatment].

PMID- 16403359
TI  - [Physician make it clear].

PMID- 16403363
TI  - [Exercise, longevity and well-being--the Osterbro study].

PMID- 16403373
TI  - Acquired bilateral nevus of Ota-like macules.
AB  - A 41-year-old woman presented with a 10-year history of grey-brown macules
      bilaterally on lateral forehead, temples, and malar aspects. Histopathologic
      examination showed dermal melanocytosis. Acquired bilateral nevus of Ota-like
      macules (Hori's nevus) is a condition usually found in middle-aged women of Asian
      descent. Pathogenesis is unknown, and effective treatment has been achieved with
      pigment-specific lasers.

PMID- 16403374
TI  - Diffuse Bier spots.
AB  - A 34-year-old man presented with a 6-month history of hypopigmented macules that
      were interspersed with blanching erythematous macules on the trunk, upper
      extremities, and lower extremities. Bier spots are small, hypopigmented macules
      that are usually found on the arms and legs of young adults. The intervening skin
      may seem erythematous but blanches with pressure so that the hypopigmented
      macules disappear. This is a benign vascular anomaly.

PMID- 16403375
TI  - Scleredema and diabetic sclerodactyly.
AB  - A 40-year-old man presented with hardening of the skin of his hands and upper
      back, which had slowly worsened with time. His medical history included insulin
      dependent diabetes mellitus since childhood. Histopathologic features of a biopsy
      specimen from the skin of his back showed a thick reticular dermis with collagen
      bundles in a haphazard array, which were separated by increased deposits of
      connective-tissue mucin. Scleredema and diabetic sclerodactyly are both well
      recognized skin findings that may occur in patients with diabetes mellitus. It is
      important to differentiate this condition from scleroderma. Treatment is
      difficult, and therefore many modalities have been used. This patient has
      improved with aminobenzoate, colchicine, and DMSO gel.

PMID- 16403376
TI  - Diffuse plane xanthomata.
AB  - An 80-year-old woman presented with yellow-orange papules and plaques on her
      scalp, back, and arms, with a Koebner reaction of the lesions on her back.
      Clinical and histopathologic findings were consistent with the diagnosis of
      diffuse plane xanthoma. Laboratory data showed normal lipid levels and an
      abnormal paraprotein in the blood. A bone marrow biopsy specimen was normal.
      Diffuse plane xanthoma is frequently associated with reticuloendothelial
      disorders, which may appear several years after the skin findings. Treatment is
      limited but may include the use of ablative lasers.

PMID- 16403377
TI  - Peripheral T-cell lymphoma.
AB  - A 32-year-old man presented with a 5-year history of cutaneous nodules on his
      head and a diffuse, lichenified eruption. Histopathologic examination showed an
      atypical lymphocytic infiltrate. Immunophenotyping studies determined that the
      lymphocyte population to be CD4-positive, with partial loss of CD3 and CD7, and
      immunogenotyping studies showed a clonal rearrangement of the T-cell receptor. A
      positron-emission tomography scan showed increased uptake in cervical, axillary,
      and inguinal lymph nodes. A diagnosis of peripheral T-cell lymphoma was made, and
      the patient is undergoing chemotherapy.

PMID- 16403378
TI  - Frontal fibrosing alopecia.
AB  - A 75-year-old woman presented with a 3-year history of progressive loss of her
      eyebrow hair and with frontal-parietal hairline recession. Multiple biopsy
      specimens supported a histopathologic diagnosis of lichen planopilaris. With
      these histolopathologic findings, and the patient's clinical presentation, a
      diagnosis of frontal fibrosing alopecia was made. Treatment to date with topical
      glucocorticoid preparations, intralesional triamcinolone injections, and
      tacrolimus ointment have been unsuccessful.

PMID- 16403379
TI  - Eosinophilic cellulitis and dermographism.
AB  - A 26-year-old man presented with a history of intermittent erythematous plaques
      on his hands and legs. A peripheral blood eosinophilia was noted. Histopathologic
      examination showed numerous eosinophils and characteristic flame figures. The
      clinical presentation and histopathologic alterations are consistent with the
      diagnosis of Wells' syndrome, which is also known as eosinophilic cellulitis.
      Wells' syndrome is a rare condition of unclear etiology. We discuss its diagnosis
      and possible association with other conditions that manifest peripheral
      eosinophilia.

PMID- 16403380
TI  - Angiokeratoma corporis diffusum (Fabry disease).
AB  - A 23-year-old man presented for cosmetic consultation for symmetrically
      distributed, red-to-purple, hyperkeratotic papules that had been present since
      early childhood. Histopathologic features included ectasia of upper dermal
      vessels with overlying hyperkeratosis. Serum alpha-galactosidase A level was
      diminished. Fabry disease is an x-linked recessive disorder in which deficiency
      of the lysosomal enzyme alpha-galactosidase A leads to progressive accumulation
      of globotriaosylceramide in vital organs. The complexity and rarity of this
      disease mandates a multidisciplinary approach that includes initiation of enzyme
      replacement therapy.

PMID- 16403381
TI  - Pityriasis rubra pilaris, type 1.
AB  - A 57-year-old woman presented with a history of dry skin with an associated
      sensation of burning and itching. It had been previously diagnosed as psoriasis.
      Clinical and histopathologic examination were consistent with pityriasis rubra
      pilaris, and treatment consisted of acitretin and narrow-band ultraviolet B
      phototherapy. Pityriasis rubra pilaris is a papulosquamous disorder of unknown
      etiology, which can be treated with retinoids, methotrexate, cyclosporine, and
      narrow-band phototherapy.

PMID- 16403382
TI  - Eumycetoma.
AB  - Eumycetoma is a localized, chronic fungal infection of skin and subcutaneous
      tissues. It is characterized by tumefaction, abscess formation, draining sinuses,
      and sclerotia (grains) within the abscesses and fistulae. Treatment of eumycetoma
      is a challenge. Relapse rates are high even when a combination of surgical and
      medical approaches is utilized. Here we report a case of eumycetoma due to
      Exophiala jeanselmei arising on the foot of a man from Trinidad, West Indies.

PMID- 16403383
TI  - Juvenile amyopathic dermatomyositis.
AB  - A 3-year-old girl presented with a 6-month history of multiple, light-pink, flat
      topped papules over the dorsal aspects of the metacarpophalangeal and
      interphalangeal joints of the hands and feet. Nailfold telangiectases, ragged
      cuticles, and a heliotrope color of the upper eyelids were also evident, but
      there was no clinical evidence of muscle weakness and levels of muscle enzymes
      were normal. A biopsy specimen from one of the papules showed a vacuolar
      interface dermatitis consistent with a diagnosis of dermatomyositis. This report
      draws attention to juvenile amyopathic dermatomyositis, which is an uncommon
      subtype of dermatomyositis with an excellent prognosis.

PMID- 16403384
TI  - X-linked recessive ichthyosis.
AB  - A 13-year-old boy presented with a lifelong history of tightly-adherent, brown,
      polygonal scales that covered the extensor surfaces of the extremities, lateral
      aspects of the trunk, and neck. The clinical presentation and the history of a
      similar skin condition in the patient's male maternal relatives helped establish
      the diagnosis of X-linked recessive ichthyosis (XLI). Systemic manifestations of
      the steroid sulfatase (STS) deficiency underlying XLI include cryptorchidism,
      asymptomatic corneal opacities, and maternal failure to progress during labor.
      Most cases of XLI are caused by deletions of the STS gene, and contiguous gene
      syndromes may occur when the deletions extend to neighboring genes on the distal
      short arm of the X chromosome.

PMID- 16403385
TI  - Lamellar ichthyosis.
AB  - A 6-year-old African boy with a history of a collodion membrane presented with
      scale in a generalized distribution and flexural accentuation. Large, brown,
      polygonal scales were present on the forehead, lateral aspects of the face, and
      extremities. The nature of the scales and the lack of erythroderma in this
      patient are consistent with a mild form of lamellar ichthyosis (LI). LI and
      nonbullous congenital ichthyosiform erythroderma (NBCIE) represent phenotypes at
      the poles of the autosomal recessive ichthyosis spectrum. Mutations in genes
      encoding transglutaminase 1 (TGM1), the ABCA12 transporter (ABCA12), ichthyin,
      lipoxygenase 3 (ALOXE3), and 12(R)-lipoxygenase (ALOX12B) have been shown to
      underlie both NBCIE and LI.

PMID- 16403386
TI  - Pityriasis rubra pilaris, type IV.
AB  - A 4-year-old girl presented with a 3-year history of demarcated, salmon-pink,
      hyperkeratotic plaques, which were symmetrically distributed on the elbows,
      knees, ankles, and dorsal aspects of the hands and feet. A diffuse, orange-pink
      palmoplantar keratoderma was also evident. Clinical and histologic findings were
      consistent with a diagnosis of pityriasis rubra pilaris (PRP), type IV
      (circumscribed juvenile). Type IV PRP develops in prepubertal children, is
      typically localized to the distal aspects of the extremities, and has an
      unpredictable course. Although ultraviolet (UV) radiation can potentially
      exacerbate PRP, our patient has improved with broad-band UVB phototherapy.

PMID- 16403387
TI  - Ichthyosiform sarcoisis.
AB  - A 39-year-old woman with a 4-year history of paraparesis developed asymptomatic,
      ichthyosiform scale on her lower extremities. The lesions consisted of polygonal,
      pigmented, adherent scales, which were most prominent on the pretibial areas. A
      biopsy specimen showed granulomatous dermatitis in a patient with pulmonary and
      neurologic sarcoidosis. Ichthyosiform sarcoidosis is a rare, specific cutaneous
      manifestation of sarcoidosis, which may be responsive to topical or systemic
      glucocorticoids.

PMID- 16403388
TI  - Nevus sebaceus.
AB  - A 35-year-old woman presented with cosmetically disturbing facial plaques, which
      had been present since birth and were consistent with nevus sebaceus on
      histopathologic examination. Nevus sebaceus is a congenital, hairless plaque,
      which is found most commonly on the scalp and face and typically becomes thicker
      and more verrucous in appearance as the patient enters adulthood. There is an
      association with benign and malignant neoplasms. Typically, these lesions are
      either removed surgically or the patients are followed clinically. Other
      therapeutic modalities utilized for cosmesis include carbon dioxide laser and
      photodynamic therapy.

PMID- 16403389
TI  - Diffuse large cell non-Hodgkin's lymphoma, CD30+, T-cell phenotype.
AB  - A 63-year-old Chinese man presented with an eczematous dermatitis that progressed
      into a multifocal nodular eruption. Histopathologic examination demonstrated a
      nodular and diffuse infiltrate in the reticular dermis, which was composed of
      lymphocytes, macrophages with granulomatous inflammation, and numerous
      eosinophils. Reactive lymphoid follicles with germinal centers also were present.
      Immunohistochemistry showed CD30 and LCA. ALK-1 and CD20 were negative. A
      diagnosis of CD30+ cutaneous T-cell lymphoma was made, and the patient is
      currently undergoing staging of his disease. Treatment options include excision
      of nodules, radiation therapy, and systemic chemotherapy.

PMID- 16403390
TI  - Piebaldism.
AB  - A 46-year-old man presented with a history of a congenital pigment disorder. On
      physical examination hypopigmented and depigmented patches were present on the
      mid-forehead, anterior chest, and extremities. He also had loss of pigment of the
      medial eyebrows and a white forelock. The patient has a family history of a
      similar congenital pigment disorder, the pattern of which is indicative of the
      autosomal dominant disorder piebaldism.

PMID- 16403391
TI  - Hereditary hemorrhagic telangiectasia.
AB  - A 45-year-old man with hereditary hemorrhagic telangiectasia (HHT) presented with
      numerous mucocutaneous telangiectases, recurrent nosebleeds, and several first
      degree relatives with similar symptoms. HHT has been linked to mutations in the
      genes endoglin and activin receptor-like kinase-1 (ALK-1), which are located on
      chromosome 9q33-34 and 12q13, respectively. The resultant proteins mediate
      binding and signaling of transforming growth factor-beta. The clinical features,
      molecular basis, and management of HHT are reviewed.

PMID- 16403392
TI  - Segmental neurofibromatosis.
AB  - A 74-year-old man presented with skin-colored nodules in his left antecubital
      fossa. The lesions had been present for 35 years and were asymptomatic. Nodules
      elsewhere on the body, cafe-au-lait spots, axillary freckling, and Lisch nodules
      were absent. No family members had similar nodules. A diagnosis of segmental
      neurofibromatosis was made, and a biopsy specimen of a nodule showed a
      neurofibroma. As the patient had no complications of neurofibromatosis 1, no
      treatment was needed.

PMID- 16403393
TI  - Multiple cutaneous and uterine leiomyomatosis (Reed's syndrome).
AB  - A 51-year-old woman with a history of uterine fibroids status post myomectomy and
      hysterectomy presented for evaluation and treatment of intermittently painful
      papules of the left shoulder. Histopathologic examination showed a proliferation
      of smooth muscle fascicles consistent with the diagnosis of cutaneous leiomyomas.
      Genetic sequencing demonstrated a novel mutation in the fumarate hydratase gene
      that confirmed the diagnosis of Reed's syndrome. A subset of individuals with
      Reed's syndrome is predisposed to develop a papillary renal-cell carcinoma, so
      appropriate radiologic examinations should be performed. Treatment of the pain
      caused by cutaneous leiomyomas includes the use of nifedipine, nitroglycerine,
      phenoxybenzamine, surgical excision, and carbon dioxide laser ablation.

PMID- 16403394
TI  - Linear porokeratosis.
AB  - A 66-year-old man presented with linear lesions of 5-years duration on his right
      lower extremity along Blaschko's lines. Physical examination showed
      hyperpigmented and violaceous papules with hypopigmented centers that were
      surrounded by fine, raised hyperkeratototic rims. The lesions were characteristic
      of porokeratosis, and the diagnosis was confirmed by histopathological
      examination. Associated medical conditions and treatment modalities are reviewed.

PMID- 16403395
TI  - Generalized granuloma annulare.
AB  - A 94-year-old man presented with a relatively asymptomatic eruption of his
      forearms, abdomen, and back comprising symmetric erythematous papules and
      plaques. Generalized granuloma annulare is an idiopathic disorder that occurs
      more commonly in older patients and is characterized by numerous flesh-colored-to
      erythematous papules. It is distinguished histologically by palisading granulomas
      with central connective tissue degeneration and with central mucin. Therapy has
      been attempted with various modalities with moderate efficacy.

PMID- 16403396
TI  - Necrobiotic xanthogranuloma.
AB  - A 67-year-old man presented with a 13-year history of slowly enlarging yellow-red
      plaques on the face and lower extremity. A biopsy specimen was consistent with
      necrobiotic xanthogranuloma. Necrobiotic xanthogranuloma is a slowly progressive
      histiocytic disease that is associated with paraproteinemia in most cases;
      however, its pathogenesis remains unclear. Although there is no first-line
      therapy, anecdotal reports have shown variable benefit with chemotherapeutic
      agents.

PMID- 16403397
TI  - Behcet disease (incomplete) and cutaneous polyarteritis nosa.
AB  - A 42-year-old man with a 2-year history of left posterior uveitis and recurrent
      oral aphthous ulcers presented for evaluation of recurrent, erythematous,
      subcutaneous, tender nodules on his lower extremities. A biopsy specimen of the
      nodules showed a medium-sized-vessel vasculitis with a mild and moderate
      inflammatory cell infiltrate in the septae and lobules of the subcutaneous
      adipose tissue. These changes were consistent with cutaneous polyarteritis
      nodosa. Behcet disease is a multisystem inflammatory disorder that includes
      recurrent oral aphthous ulcers, and at least two of the following features:
      recurrent genital ulcers, eye lesions, skin lesions, and a positive pathergy
      test. Behcet disease and cutaneous polyarteritis nodosa have rarely been
      described in conjunction, and the suggestion has been raised that cutaneous
      polyarteritis-nodosa-like lesions may actually be a cutaneous marker of Behcet
      disease.

PMID- 16403398
TI  - Chronic cutaneous lupus erythematosus mimicking pseuxanthoma elasticum.
AB  - 54-year-old woman presented with an unusual presentation of chronic cutaneous
      lupus erythematosus that mimicked pseudoxanthoma elasticum. The lesions were
      asymptomatic, 2-3 mm, skin-colored, smooth papules without scale or erythema;
      they were located on the chin, medial malar cheeks, and upper lip. She previously
      failed traditional treatments, which included hydroxychloroquine and dapsone. The
      patient responded to thalidomide with a reduction in appearance and number of
      lesions.

PMID- 16403399
TI  - Where are we headed: the value of updating guidelines.

PMID- 16403400
TI  - The CMS 2006 Quality in Oncology Demonstration Project and NCCN Guidelines.

PMID- 16403401
TI  - Surviving the perfect storm: an RVU-based model to evaluate the continuing impact
      of MMA on the practice of oncology.
AB  - The Resource-Based Relative Value Scale (RBRVS) system instituted by Centers for
      Medicare and Medicaid Services has lead to the implementation of a new financial
      analysis paradigm based on relative value units (RVUs). RVU-based financial tools
      have great potential to allow in-depth analysis of all components of the cancer
      care delivery system. Because all medical oncology practices must become
      conversant in RVU terminology and methodology, RVU-based financial tools will
      allow standardization and benchmarking for intra- and interpractice comparisons.
      Understanding this approach is essential for sound business management. The
      emotional and financial pressures facing the medical oncologist in private
      practice are enormous, with no real relief in sight. The complexity of managing
      the business of private practice oncology rivals that of managing the complexity
      of cancer care. With anticipated reductions in total net revenue per clinical
      treatment protocol per course of care, funds available for providers and their
      practices will be severely reduced. Only those practices with superlative RVU
      based cost and revenue accounting systems will be able to prospectively and
      efficiently manage their businesses. Clearly, management of the Oncology Practice
      Econometric Model (OPEM) expense RVU or similar RVU-based data will be required
      for survival. The purpose of this article is to explore an RVU-based model to
      analyze the professional, infusion, and therapeutic components of contemporary
      cancer care.

PMID- 16403402
TI  - Acute myeloid leukemia clinical practice guidelines in oncology.

PMID- 16403403
TI  - Strategies for the treatment of acute promyelocytic leukemia.
AB  - The outcome of acute promyelocytic leukemia (APL) has improved dramatically
      during the past 40 years. Insights into the genetic and biologic mechanisms of
      APL lead to the development of specific and effective therapeutic strategies.
      This article discusses the therapeutic interventions that transformed APL from
      one of the most lethal leukemias to one that is highly curable.

PMID- 16403404
TI  - Non-transplant therapy for older adults with acute myeloid leukemia.
AB  - Acute myeloid leukemia is a disease of older adults, with a median age at
      diagnosis of 68 years. This group represents a high-risk population, because
      inherent disease characteristics predict for resistance to chemotherapy and
      advanced age is accompanied by high treatment-related mortality. Standard
      remission-induction and postremission therapy can result in a median disease-free
      survival of 10 months and rare long-term survival. Efforts to improve outcomes
      have not made a major impact on complete remission rates of 40% to 60%, or on
      overall survival. Newer therapies, divided into aggressive and nonaggressive
      approaches, focus on targeting the disease biology specific to older adults and
      on maximizing quality of life. Clinical trials should be considered at every
      stage of treatment in this group of patients.

PMID- 16403405
TI  - Myelodysplastic syndromes clinical practice guidelines in oncology.

PMID- 16403406
TI  - Developmental therapeutics for myelodysplastic syndromes.
AB  - The management strategy for patients with myelodysplastic syndromes (MDS) has
      evolved from sole reliance on supportive measures to active treatment guided by
      disease risks. Recent progress in understanding the molecular pathogenesis of MDS
      has accelerated the discovery of new therapeutic targets, and consequently
      launched the development of several novel therapeutics that are currently in
      varied stages of clinical testing. One such agent is lenalidomide, which has
      shown remarkable effectiveness in the cytogenetically defined subset of MDS with
      the chromosome 5q31 deletion. The advent of new and effective targeted
      therapeutics may beneficially affect outcomes of an ever-increasing number of
      patients with MDS. This discussion summarizes the preliminary results of selected
      novel therapeutics.

PMID- 16403407
TI  - Six (or more) drugs in search of a mechanism: DNA methyltransferase and histone
      deacetylase inhibitors in the treatment of myelodysplastic syndromes.
AB  - The clinical activity of the DNA methyltransferase inhibitors 5-azacitidine and
      2'-deoxy-5-azacytidine in myelodysplastic syndromes (MDS) suggests that
      epigenetic modulation of gene transcription may play an important pathogenetic
      role in the development and expression of these diseases. Approximately 50% of
      patients treated with these compounds experience hematologic improvement, making
      these the most active single agents for unselected patients with MDS. Responses
      include complete and partial hematologic responses. Two randomized trials have
      shown that the use of these drugs significantly alters the natural history of MDS
      compared with supportive care. Histone deacetylase inhibitors, which may also
      impact the expression of genes through epigenetic mechanisms, seem to have
      measurable activity in MDS in preliminary studies. Histone deacetylase inhibitors
      are most likely used in combination with other agents, including DNA
      methyltransferase inhibitors. Despite the clinical activity of these classes of
      drugs, there is no conclusive evidence that their clinical activity is
      attributable to their impact on the epigenome. Such information will be critical
      in the development of more effective congeners and drug combinations in ongoing
      attempts to improve the outcome of patients with MDS.

PMID- 16403408
TI  - Myelodysplastic syndromes: iron overload consequences and current chelating
      therapies.
AB  - Chronic red blood cell transfusion support in patients with myelodysplastic
      syndromes (MDS) is often necessary but may cause hemosiderosis and its
      consequences. The pathophysiologic effects of iron overload relate to increased
      non-transferrin bound iron generating toxic oxygen free radicals. Studies in
      patients with MDS and thalassemia major have shown adverse clinical effects of
      chronic iron overload on cardiac function in patients who underwent
      polytransfusion. Iron chelation therapy in patients with thalassemia who were
      effectively chelated has prevented or partially reversed some of these
      consequences. A small group of patients with MDS who had undergone effective
      subcutaneous desferrioxamine (DFO) chelation for 1 to 4 years showed substantial
      hematologic improvements, including transfusion independence. However, because
      chronic lengthy subcutaneous infusions of DFO in elderly patients have logistic
      difficulties, this chelation therapy is generally instituted late in the clinical
      course. Two oral iron chelators, deferiprone (L1) and deferasirox (ICL670),
      provide potentially useful treatment for iron overload. This article reviews data
      indicating that both agents are relatively well tolerated, were at least as
      effective as DFO for decreasing iron burdens in comparative thalassemia trials,
      and (for deferiprone) were associated with improved cardiac outcomes. These
      outcomes could potentially alter the tissue siderosis-associated morbidity of
      patients with MDS, particularly those with pre-existing cardiac disease.

PMID- 16403409
TI  - Conditional expression of women's desires and men's mate guarding across the
      ovulatory cycle.
AB  - Thirty-eight normally cycling women provided daily reports of sexual interests
      and feelings for 35 days. Near ovulation, both pair-bonded and single women
      reported feeling more physically attractive and having greater interest in
      attending social gatherings where they might meet men. Pair-bonded women who were
      near ovulation reported greater extra-pair flirtation and greater mate guarding
      by their primary partner. As predicted, however, these effects were exhibited
      primarily by women who perceived their partners to be low on hypothesized good
      genes indicators (low in sexual attractiveness relative to investment
      attractiveness). Ovulation-contingent increases in partner mate guarding were
      also moderated by female physical attractiveness; midcycle increases in mate
      guarding were experienced primarily by less attractive women, whereas more
      attractive women experienced relatively high levels of mate guarding throughout
      their cycle. These findings demonstrate ovulation-contingent shifts in desires
      and behaviors that are sensitive to varying fitness payoffs, and they provide
      support for the good genes hypothesis of human female extra-pair mating. The
      daily assessment method provides an important supplement to existing studies
      using scheduled laboratory visits as the purpose of the study (examining cycle
      related variation) is not known by participants.

PMID- 16403410
TI  - Digit ratio (2D:4D) and physical fitness in males and females: Evidence for
      effects of prenatal androgens on sexually selected traits.
AB  - It has been suggested that male achievement in sports and athletics is correlated
      with a putative measure of prenatal testosterone the 2nd to 4th digit ratio
      (2D:4D). It is not known whether this association also extends to females, or
      whether the association results from an effect of testosterone on behavior (such
      as exercise frequency) or on physical fitness. Here, we report for the first time
      data from two studies which consider associations between 2D:4D and physical
      fitness in females in addition to males: Study I--in a sample of teenage boys (n
      = 114) and girls (n = 175), their 'physical education grade' was negatively
      associated with 2D:4D of the right hand (boys), and right and left hand (girls),
      and Study II-among a sample of young men (n = 102) and women (n = 77), a
      composite measure of physical fitness was negatively related to right hand 2D:4D
      in men and left hand 2D:4D in women. We conclude that 2D:4D is negatively related
      to physical fitness in both men and women. In Study II, there was evidence that
      the relationship between physical fitness and 2D:4D in men was mediated through
      an association with exercise frequency. Thus, 2D:4D in males may be a negative
      correlate of frequent exercise which then relates to achievement in sports and
      athletics.

PMID- 16403411
TI  - Immuno-monitoring of CD8+ T cells in whole blood versus PBMC samples.
AB  - The study of natural T cell responses against pathogens or tumors, as well as the
      assessment of new immunotherapy strategies aimed at boosting these responses,
      requires increasingly precise ex vivo analysis of blood samples. For practical
      reasons, studies are often performed using purified PBMC samples, usually
      cryopreserved. Here, we report on FACS analyses of peripheral blood T cells,
      performed by direct antibody staining of non-purified total blood. For
      comparison, fresh PBMC, purified by Ficoll, were analysed. Our results show that
      the latter method can induce a bias in subpopulation distribution, in particular
      of CD8+ T cells, and sometimes lead to inaccurate measurement of antigen specific
      CD8+ T cell responses. Direct analysis of total blood can be applied to
      longitudinal immuno-monitoring of T cell-based therapy. While the need to purify
      and cryopreserve PBMC for subsequent studies is obvious, the use of whole blood
      has the advantage of providing unbiased results and only small amounts of blood
      are used.

PMID- 16403412
TI  - Alcohol-induced impairment of neuronal nitric oxide synthase (nNOS)-dependent
      dilation of cerebral arterioles: role of NAD(P)H oxidase.
AB  - The goal of the present study was to determine the role of NAD(P)H oxidase in
      alcohol consumption-induced impairment of nNOS-dependent reactivity in cerebral
      arterioles. Sprague-Dawley rats were fed an alcohol diet for 2-3 months. We
      measured the effects of acute (1 hour) and chronic (1 month) treatment with a
      NAD(P)H oxidase inhibitor, apocynin, on responses of parietal pial arterioles to
      nNOS-dependent agonists (NMDA and kainate) and an nitric oxide synthase (NOS)
      independent agonist (nitroglycerin). In addition, we measured the expression of
      NAD(P)H oxidase subunits and superoxide production in parietal cortex. Topical
      application of NMDA and kainate produced dose-related dilation of pial
      arterioles. However, the magnitude of vasodilation to these agonists was
      significantly less in alcohol-fed rats. Treatment with apocynin (acute and
      chronic) did not alter vasodilation in nonalcohol-fed rats, but significantly
      improved vasodilation in alcohol-fed rats. Response of pial arterioles to
      nitroglycerin was similar in nonalcohol-fed and alcohol-fed rats, and was not
      affected by apocynin. In addition, we found an up-regulation of gp91phox and
      p47phox in parietal cortex of alcohol-fed rats. Finally, alcohol consumption
      produced an increase in superoxide production under basal conditions and in the
      presence of NADPH. Acute treatment with apocynin suppressed alcohol consumption
      induced superoxide generation. Our findings suggest that NAD(P)H oxidase plays an
      important role in chronic alcohol consumption-induced impairment of nNOS
      dependent dilation of cerebral arterioles.

PMID- 16403413
TI  - The co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins.
AB  - The action of the molecular chaperone Hsp90 is essential for the activation and
      assembly of an increasing number of client proteins. This function of Hsp90 has
      been proposed to be governed by conformational changes driven by ATP binding and
      hydrolysis. Association of co-chaperones and client proteins regulate the ATPase
      activity of Hsp90. Here, we have examined the inhibition of the ATPase activity
      of human Hsp90beta by one such co-chaperone, human p23. We demonstrate that human
      p23 interacts with Hsp90 in both the absence and presence of nucleotide with a
      higher affinity in the presence of the ATP analogue AMP-PNP. This is consistent
      with an analysis of the effect of p23 on the steady-state kinetics that revealed
      a mixed mechanism of inhibition. Mass spectrometry of the intact Hsp90.p23
      complex determined the stoichiometry of binding to be one p23 to each subunit of
      the Hsp90 dimer. p23 was also shown to interact with a monomeric, truncated
      fragment of Hsp90, lacking the C-terminal homodimerisation domain, indicating
      dimerisation of Hsp90 is not a prerequisite for association with p23. Complex
      formation between Hsp90 and p23 increased the apparent affinity of Hsp90 for AMP
      PNP and completely inhibited the ATPase activity. We propose a model where the
      role of p23 is to lock individual subunits of Hsp90 in an ATP-dependent
      conformational state that has a high affinity for client proteins.

PMID- 16403414
TI  - Human Jagged 1 mutants cause liver defect in Alagille syndrome by overexpression
      of hepatocyte growth factor.
AB  - Alagille syndrome (AGS, MIM 118450) is an autosomal dominant inherited disease.
      Paucity of interlobular bile ducts is one of the major abnormalities. To explore
      the molecular mechanism by which mutation in the human Jagged 1 gene (JAG1, MIM
      601920) causes liver defects, we investigated the gene regulation of JAG1 to
      hepatocyte growth factor gene (HGF). By transfecting wild-type and mutant JAG1
      into COS-7 cells in vitro, we found that HGF is a target gene of JAG1 downstream.
      Wild-type JAG1 is inhibitory for HGF expression and mutant JAG1s relieve the
      inhibition. Several domain disruptions in mutant JAG1 protein reveal a reduced
      inhibition to HGF expression at different levels. JAG1 mutations actually result
      in HGF overexpression. Furthermore, JAG1 controls HGF expression by a dosage
      dependent regulation and Notch2 signaling seems to mediate JAG1 function. Given
      that HGF plays a critical role in differentiation of hepatic stem cells,
      overexpression of HGF acts on off-balanced cell fate determination in AGS
      patients. Hepatic stem cells may differentiate towards more hepatocytes but less
      biliary cells, thus causing the paucity of interlobular bile ducts in liver
      development of AGS. Our novel findings demonstrated that dosage-dependent
      regulation by mutations of JAG1 is a fundamental mechanism for liver abnormality
      in AGS.

PMID- 16403415
TI  - Effect of the carbon coating in Fe-C-TiO(2) photocatalyst on phenol decomposition
      under UV irradiation via photo-Fenton process.
AB  - Fe-C-TiO(2) photocatalysts which contained the residue carbon (0.2-3.3 mass%)
      were prepared from a mixture of TiO(2) and FeC(2)O(4) through the heating at 673
      1173 K in Ar. These photocatalysts did not show a high adsorption of phenol, but
      they were active in photo-Fenton reactions during decomposition of phenol under
      UV irradiation with addition of H(2)O(2). It was proved that Fe(2+) governed the
      photoactivity of Fe-C-TiO(2) photocatalysts, it decreased with heat-treatment
      temperature above 773 K. For comparison, Fe-TiO(2) photocatalyst was prepared by
      heating TiO(2) and FeC(2)O(4) at 823 K in air for 3h. Phenol decomposition was
      going much slower on Fe-TiO(2) photocatalyst in comparison with Fe-C-TiO(2), of
      which mechanism was different, on the former phenol was decomposed by the radical
      reaction, on the latter through a complex reaction with iron and intermediates of
      phenol decomposition. Therefore carbon-coating TiO(2) was found to be
      advantageous for mounting iron and its application for the phenol decomposition
      via photo-Fenton process.

PMID- 16403416
TI  - Treatability of water-based paint wastewater with Fenton process in different
      reactor types.
AB  - Water-based paint wastewater which is formed during the coating step of metal
      surfaces performed with various spray processes include binders, pigments and
      additives. Binders and other additives may also affect the toxicity of the paint
      depending on the specific characteristics of the paint. This study deals with
      Water-based paint wastewater, which is hard to treat. Fenton oxidation process
      was principally used to treat the wastewater. Treatability runs were carried out
      by using rust (oxidized iron) particles obtained as a waste of the metal rolling
      process, as the Fenton's catalyst. In order to change the variables such as
      dimensions of the column, packing material size, reactive dosage, pH value and
      reaction time, the experiments on the basis of packed columns and mixed reactors
      were carried out to increase the COD removal. COD eliminations with pH adjustment
      were about 20%. With the contribution of Fenton process in both column and mixed
      reactor studies, the COD removal was improved by about 80%.

PMID- 16403417
TI  - Breakdown products on metabolic pathway of degradation of benz[a]anthracene by a
      ligninolytic fungus.
AB  - Cultures of the ligninolytic fungus Irpex lacteus incubated in a nutrient liquid
      medium degraded more than 70% of the initially applied benz[a]anthracene within
      14 days. At the first step of metabolization, benz[a]anthracene was transformed
      via a typical pathway of ligninolytic fungi to benz[a]anthracene-7,12-dione
      (BaAQ). The product was further transformed by at least two ways, whereas one is
      complied with the anthracene metabolic pathway of I. lacteus. Benz[a]anthracene
      7,12-dione was degraded to 1,2-naphthalenedicarboxylic acid and phthalic acid
      that was followed with production of 2-hydroxymethyl benzoic acid or monomethyl
      and dimethylesters of phthalic acid. Another degradation product of BaAQ was
      identified as 1-tetralone. Its transformation via 1,4-naphthalenedione, 1,4
      naphthalenediol and 1,2,3,4-tetrahydro-1-hydroxynaphthalene resulted again in
      phthalic acid. None of the intermediates were identified as dead-end metabolites.
      Metabolites produced by ring cleavage of benz[a]anthracene using the ligninolytic
      fungus are firstly presented in this work.

PMID- 16403418
TI  - Impacts of COD and DCP loading rates on biological treatment of 2,4
      dichlorophenol (DCP) containing wastewater in a perforated tubes biofilm reactor.
AB  - Biofilm processes offer considerable advantages for biological treatment of
      chlorophenol containing wastewaters since such industrial effluents are difficult
      to treat by conventional activated sludge processes. A rotating perforated tubes
      biofilm reactor (RTBR) was developed and used for treatment of 2,4-dichlorophenol
      (DCP) containing synthetic wastewater. Effects of COD and DCP loading rates on
      COD, DCP and toxicity removals were investigated. Percent COD removal decreased
      and effluent COD increased with increasing COD and DCP loading rates due to toxic
      effects of high DCP content in the feed. DCP and toxicity removals showed similar
      trends. As the DCP loading rate increased the effluent DCP content increased
      yielding high toxicity levels in the effluent. COD and DCP loading rates should
      be below 90gCODm(-2)d(-1) and 2.8gDCPm(-2)d(-1) in order to obtain more than 90%
      DCP and toxicity removals. However, DCP loading rates lower than 1gDCPm(-2)d(-1)
      are required to obtain more than 90% COD removal. Empirical equations were
      developed to estimate percent COD, DCP and toxicity removals as functions of COD
      and DCP loading rates. The coefficients of the empirical equations were
      determined by using the experimental data. Empirical model predictions for
      percent COD, DCP and toxicity removals were in good agreement with the
      experimental data.

PMID- 16403419
TI  - Depositional flux of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans in an urban setting.
AB  - Dry and wet deposition fluxes of the PCDD/F substituted congeners were measured
      at two different sites (Clinton Drive and Lang Road) in Houston, TX between
      December 2003 and April 2004. Average total dry deposition fluxes of 351 and
      125pgm(-2)d(-1) were found at Clinton Drive and Lang Road, respectively. A wet
      deposition flux of 2.873pgm(-2)d(-1) was measured at the Clinton Drive site. The
      results indicated that the dry deposition process exhibited spatial variability.
      In addition, the results also demonstrated that precipitation, although
      intermittent, is the most important mechanism for the removal of dioxins from
      atmosphere in the area of study. Combining the contributions of the dry and wet
      deposition processes at Clinton Drive resulted in a total bulk deposition flux of
      527pg m(-2)d(-1). The total dry and wet deposition fluxes were dominated by OCDD
      followed by 1,2,3,4,6,7,8-HpCDD at both sites. Overall average dry deposition
      velocities of 0.35 and 0.15cms(-1) were calculated at Clinton Drive and Lang Road
      sites, respectively. While these velocities were similar to velocities observed
      in other geographical areas, the contribution of OCDD to the total deposition
      flux in Houston was significantly higher, probably reflecting the unique nature
      and character of Houston dioxin sources. The results also showed that lower
      chlorinated congeners, primarily present in the gas phase, are more likely to be
      removed from the atmosphere by precipitation. Relationships between the detected
      congeners in the dry deposition samples and other routinely measured air
      pollutants/meteorological parameters were found. The results showed that in
      general, the dry deposition of these congeners was consistently negatively
      correlated with SO(2) and NO(x) concentrations in the air and positively
      correlated with relative humidity. However, more research is needed to ascertain
      those correlations.

PMID- 16403420
TI  - Perfluorinated chemicals in relation to other persistent organic pollutants in
      human blood.
AB  - In order to evaluate blood levels of some perfluorinated chemicals (PFCs) and
      compare them to current levels of classical persistent organic pollutants (POPs)
      whole blood samples from Sweden were analyzed with respect to 12 PFCs, 37
      polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (DDE),
      hexachlorobenzene (HCB), six chlordanes and three polybrominated diphenyl ethers
      (PBDEs). The median concentration, on whole blood basis, of the sum of PFCs was
      20-50 times higher compared to the sum of PCBs and p,p'-DDE, 300-450 times higher
      than HCB, sum of chlordanes and sum of PBDEs. Estimations of the total body
      amount of PFCs and lipophilic POPs point at similar body burdens. While levels of
      for example PCBs and PBDEs are normalized to the lipid content of blood, there is
      no such general procedure for PFCs in blood. The distributions of a number of
      perfluorinated compounds between whole blood and plasma were therefore studied.
      Plasma concentrations were higher than whole blood concentrations for four
      perfluoroalkylated acids with plasma/whole blood ratios between 1.1 and 1.4,
      whereas the ratio for perflurooctanesulfonamide (PFOSA) was considerably lower
      (0.2). This suggests that the comparison of levels of PFCs determined in plasma
      with levels determined in whole blood should be made with caution. We also
      conclude that Swedish residents are exposed to a large number of PFCs to the same
      extent as in USA, Japan, Colombia and the few other countries from which data is
      available today.

PMID- 16403421
TI  - The partitioning and modelling of pesticide parathion in a surfactant-assisted
      soil-washing system.
AB  - Soil sorption of organic pollutants has long been a problematic in the soil
      washing process because of its durability and low water solubility. This paper
      discussed the soil washing phenomena over a wide range of parathion
      concentrations and several soil samples at various fractions of organic content
      (foc) levels. When parathion dosage is set below the water solubility, washing
      performance is stable for surfactant concentrations above critical micelle
      concentration (cmc) and it is observed that more than 90% of parathion can be
      washed out when dosage is five times lower than the solubility limit. However,
      such trends change when non-aqueous phase liquids (NAPL) is present in the
      system. Parathion extraction depends very much on the surfactant dosage but is
      not affected by the levels of foc in the system. In between the extreme parathion
      dosage, a two-stage pattern is observed in these boundary regions. Washing
      performance is first increased with additional surfactant, but the increase slows
      down gradually since the sorption sites are believed to be saturated by the huge
      amount of surfactant in the system. A mathematical model has included foc to
      demonstrate such behavior and this can be used as a prediction for extraction.

PMID- 16403422
TI  - Distribution of nociceptin and Ro64-6198 activated [35S]-GTPgammaS binding in the
      rat brain.
AB  - The peptide, nociceptin, was discovered as the endogenous ligand for the opioid
      like receptor, ORL1. Since its discovery, this peptide has been shown to modulate
      the perception of pain, modulate feeding and produce behavioral effects in rodent
      models of mood disorders. Recently, the non-peptide agonist {(1S,3aS)-8
      (2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4
      one} (Ro64-6198) of the ORL1 receptor has been reported in the literature. In the
      present study, we compared the distribution and potency of Ro64-6198 with
      nociceptin for their ability to stimulate [(35)S]-GTPgammaS binding to sections
      of rat brain. In initial studies, Ro64-6198 inhibited (125)I-nociceptin binding
      to the hORL1 receptors with a K(i) of 1.75 nM compared with 0.20 nM for
      nociceptin. To assess agonist potency in a whole cell assay, a cell line
      expressing the hORL1 receptor and G(alpha15) was created and used for calcium
      mobilization studies. In this assay system, Ro64-6198 increased intracellular
      calcium with an EC(50) of 52nM compared with 24 nM for nociceptin. Having
      verified the agonist properties of Ro64-6198, we then assessed the potency and
      distribution of ORL1 receptor activation in rat brain sections. In dose-response
      studies, Ro64-6198 increased [(35)S]-GTPgammaS binding to a variety of brain
      regions with EC(50) values ranging from 84.9 to 2,143 nM depending on the brain
      regions evaluated. These potencies were similar to that seen for nociceptin, but
      substantially lower than values established using [(125)I] nociceptin binding to
      the cloned human ORL1 receptor. In general, the brain distribution of agonist
      stimulated [(35)S]-GTPgammaS binding was similar when either Ro64-6198 or
      nociceptin were used. Using these techniques, we have demonstrated, for the first
      time that Ro64-6198 activates [(35)S]-GTPgammaS binding to rat brain sections and
      this compound stimulates a similar population of receptors as nociceptin.

PMID- 16403423
TI  - Renovascular disease imaging: today more than ever the invasive cardiologist may
      make the difference.
AB  - Doppler ultrasound (US), computed tomography (CT) and magnetic resonance imaging
      (MRI) are gaining wide acceptance as gold standard for diagnosing peripheral
      artery disease at thoracic and abdominal aorta level and infrainguinal arteries.
      A different case is that of renal artery stenosis (RAS): noninvasive techniques,
      CT and MRI in particular, failed to become the new gold standard. Image
      interpretation and artifacts seems to invalidate MRI and CT sensitivity and
      specificity that remain quite low. The debacle of noninvasive imaging of renal
      arteries may have important reflexes on the invasive cardiology practice. In the
      light of the results of noninvasive tests for renal artery stenosis, the
      angiography of renal vessels performed at the time of coronary artery angiography
      may became a new tool for invasive professional to optimize the diagnosis of
      renal artery stenosis at least in patients scheduled for coronary angiography.
      The invasive cardiologist, today more than ever, has the chance to really impact
      the diagnosis and therapy of patients with renovascular disease and the prognosis
      of patients with both coronary artery and renal artery disease.

PMID- 16403424
TI  - Gastric myoelectrical activity as an index of emotional arousal.
AB  - Autonomic nervous system parameters such as electrodermal activity, heart rate,
      and facial EMG have been utilized extensively as measures of emotional arousal.
      One measure that has rarely been employed in this setting is gastric
      myoelectrical activity, despite the fact that "gut feelings" have an obvious and
      even profound role in everyday emotional life. It has been shown that the
      gastrointestinal system changes wall tonus and contraction rate during stressful
      tasks. However, the effects of emotionally salient stimuli on gastrointestinal
      motility have scarcely been studied. In the current study, emotional film clips
      designed to elicit happiness, disgust, fear, sadness, or no emotion (neutral)
      were presented to 16 normal participants. Electrogastrogram (EGG), skin
      conductance, and heart rate were measured while the participants viewed the film
      clips, and participants rated subjective arousal intensity and pleasantness of
      the film clips. We found that emotional film clips reliably induced the intended
      subjective feeling states. Also, EGG peak amplitudes in fear, disgust, sadness
      and happiness were higher than in the no emotion condition. There was a strong
      positive correlation (r=0.64) between EGG peak amplitude and subjective ratings
      of arousal. This is the first evidence that gastric myoelectrical activity is
      strongly correlated with arousal ratings to emotionally salient stimuli, and it
      suggests that EGG may add useful information about how the body contributes to
      the phenomenology of emotion and feeling.

PMID- 16403425
TI  - Reconstruction of fingertip defects with the neurovascular tranquilli-leali flap.
AB  - For many years, bipedicled palmar advancement flaps were used rarely in fingers
      because they sacrificed the dorsal branches of the digital arteries, risking
      dorsal skin necrosis. In 1995, a short bipedicled neurovascular VY advancement
      flap raised distally to the PIP flexion crease, which spared the dorsal blood
      supply, was described by Elliot et al. (1995). This paper includes an anatomical
      study on 28 fresh cadaver fingers to evaluate the advancement potential of this
      flap. It also reviews 22 fingertip reconstructions in 22 patients using this
      flap. The mean advancement of the flap in the cadaver study was 14 (range 10-16)
      mm. This procedure gave good clinical results in respect of healing, sensibility,
      bone cover and appearance. Complications occurred in four fingers (18%), viz. two
      infections, one neuroma and one stiff proximal interphalangeal joint. Our study
      suggests that this flap can be used to treat fingertip defects of a size of
      approximately half of the pulp of the distal phalangeal segment of the finger.

PMID- 16403426
TI  - The Pole3 bidirectional unit is regulated by MYC and E2Fs.
AB  - Pole3 (DPB4/YBL1/CHRAC17) is one of the subunits of the DNA polymerase e. It
      contains a histone-like domain required for the hererodimerization with its Pole4
      (DPB3) partner. In another interaction, Pole3 heterodimerizes with YCL1/CHRAC15
      and associates with the ACF1/SNF2H remodelling complex. We find that the Pol3
      gene is regulated in starved NIH3T3 fibroblasts upon induction with serum, with a
      peak at the entry in the S phase. We characterized the Pole3 promoter, which is
      linked bidirectionally to C9Orf46, a gene of unknown function: it has no CCAAT
      nor TATA-boxes, and contains an E box and two potential E2F sites. Mutagenesis
      analysis points to a minimal promoter region as sufficient for activation; the E
      box and a neighbouring direct repeat are important for regulation. Cell-cycle
      regulation was reproduced in stable clones and an additional E2F site was found
      to be important. Chromatin immunoprecipitation analysis indicates that E2F1/4, as
      well as MYC, are associated with the Pole3 promoter in a phase-specific way.
      These data highlight coregulation of a histone-like gene with core histones upon
      DNA synthesis, and represent a first dissection of the interplay between two
      essential cell-cycle regulators on a bidirectional promoter.

PMID- 16403427
TI  - Detection of dimethylarginines in protein hydrolysates by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - We report a method to detect the presence of dimethylarginines on proteins.
      Peptides with dimethylarginines were hydrolyzed in acid. The hydrolysates were
      subjected to matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometric analysis using a mixture of alpha-cyano-4-hydroxycinnamic
      acid and nitrocellulose as matrix. Both asymmetric omega-N(G),N(G)
      dimethylarginine and symmetric omega-N(G),N(G')-dimethylarginine give a clear
      signal at m/z 203. Recombinant Sbp1p modified by Hmt1p in vivo were isolated by
      affinity chromatography followed by electrophoresis on a polyacrylamide gel and
      subjected to acid hydrolysis. MALDI-TOF analysis of the acid hydrolysates
      confirmed the presence of dimethylarginines. The detection limit of the method is
      estimated at approximately 1pmol of protein.

PMID- 16403428
TI  - SWTY--a general peptide probe for homogeneous solution binding assay of 14-3-3
      proteins.
AB  - Dimeric 14-3-3 proteins exert diverse functions in eukaryotes by binding to
      specific phosphorylated sites on diverse target proteins. Critical to the
      physiological function of 14-3-3 proteins is the wide range of binding affinity
      to different ligands. The existing information of binding affinity is mainly
      derived from nonhomogeneous-based methods such as surface plasmon resonance and
      quantitative affinity precipitation. We have developed a fluorescence anisotropy
      peptide probe using a genetically isolated 14-3-3-binding SWTY motif. The
      synthetic 5-(and-6)-carboxyfluorescein(FAM)-RGRSWpTY-COOH peptide, when bound to
      14-3-3 proteins, exhibits a seven-fold increase in fluorescence anisotropy.
      Different from the existing assays for 14-3-3 binding, this homogeneous assay
      tests the interaction directly in solution. Hence it permits more accurate
      determination of the dissociation constants of 14-3-3 binding molecules.
      Protocols for a simple mix-and-read format have been developed to evaluate 14-3-3
      protein interactions using either purified recombinant 14-3-3 fusion proteins or
      native 14-3-3s in crude cell lysate. Optimal assay conditions for high-throughput
      screening for modulators of 14-3-3 binding have been determined.

PMID- 16403430
TI  - Colorimetric assay for the quantitation of iron in yeast.

PMID- 16403429
TI  - Restriction enzyme cleavage of fluorescently labeled DNA fragments--analysis of
      the method and its usage in examination of digestion completeness.
AB  - Restriction enzymes have proven to be among the most valuable tools in molecular
      biology. In this work, we demonstrate that the cleavage of fluorescently labeled,
      PCR-amplified DNA can be used as a simple and highly sensitive technique for
      detection of sequences present in a percentage as low as 0.6% in a DNA pool. Due
      to the fact that fluorescent labeling of DNA fragments enables such sensitive
      detection and quantification of restriction enzyme cleavage, the method was
      further exploited in monitoring of the enzymatic digestion completeness and in
      determination of factors that influence restriction enzyme effectiveness. We
      analyzed the activity of six restriction endonucleases; the percentage of
      uncleaved DNA fragments predominantly ranged between 2.0 and 2.5 and the highest
      value was 8.00%. We conclude that, since the enzymatic digestion completeness may
      not always be assured, each assay based on restriction enzyme cleavage that is
      intended to be used in investigations of heterogeneity in a DNA pool should be
      constructed so that the presence of cleaved sequences is the indication of pool
      nonuniformity. When the presence of uncleaved sequences indicates pool
      heterogeneity, the results could be misleading due to possible incompleteness of
      enzymatic cleavage.

PMID- 16403431
TI  - Perinatal corticosteroid effect on amygdala and hippocampus volume during brain
      development in the rat model.
AB  - Exposure of the fetus to corticosteroid during brain development has been
      suggested to cause permanent change in brain structure and has been associated
      with long term cognitive, behavioral and emotional impairment. We evaluated the
      effect of perinatal corticosteroid, at a dose similar to that which human fetuses
      are exposed, on cerebral cortex, corpus collosum, hippocampus, dentate gyrus and
      amygdala in a rat model. Rat pups were given betamethasone at day 1 (P1). Brain
      sections from the rat pups at postnatal day 45 (P45) were then analyzed. No
      differences were noted in the volumes of cerebral cortex, corpus collosum,
      hippocampus, dentate gyrus, or three nuclei of the amygdala compared to the
      control and sham groups. We concluded that a single course of betamethasone, at a
      comparable dose to that which the human fetus is exposed in clinical practice,
      had no effect on these regional brain volumes at this stage of development.

PMID- 16403432
TI  - A dip in the chlorophyll fluorescence induction at 0.2-2 s in Trebouxia
      possessing lichens reflects a fast reoxidation of photosystem I. A comparison
      with higher plants.
AB  - An unusual dip (compared to higher plant behaviour under comparable light
      conditions) in chlorophyll fluorescence induction (FI) at about 0.2-2 s was
      observed for thalli of several lichen species having Trebouxia species (the most
      common symbiotic green algae) as their native photobionts and for Trebouxia
      species cultured separately in nutrient solution. This dip appears after the
      usual O(J)IP transient at a wide range of excitation light intensities (100-1800
      micromol photons m(-2) s(-1)). Simultaneous measurements of FI and 820-nm
      transmission kinetics (I(820)) with lichen thalli showed that the decreasing part
      of the fluorescence dip (0.2-0.4 s) is accompanied by a decrease of I(820), i.e.,
      by a reoxidation of electron carriers at photosystem I (PSI), while the
      subsequent increasing part (0.4-2 s) of the dip is not paralleled by the change
      in I(820). These results were compared with that measured with pea leaves
      representatives of higher plants. In pea, PSI started to reoxidize after 2-s
      excitation. The simultaneous measurements performed with thalli treated with
      methylviologen (MV), an efficient electron acceptor from PSI, revealed that the
      narrow P peak in FI of Trebouxia-possessing lichens (i.e., the I-P-dip phase)
      gradually disappeared with prolonged MV treatment. Thus, the P peak behaves in a
      similar way as in higher plants where it reflects a traffic jam of electrons
      induced by a transient block at the acceptor side of PSI. The increasing part of
      the dip in FI remained unaffected by the addition of MV. We have found that the
      fluorescence dip is insensitive to antimycin A, rotenone (inhibitors of cyclic
      electron flow around PSI), and propyl gallate (an inhibitor of plastid terminal
      oxidase). The 2-h treatment with 5 microM nigericin, an ionophore effectively
      dissipating the pH-gradient across the thylakoid membrane, did not lead to
      significant changes either in FI nor I(820) kinetics. On the basis of the
      presented results, we suggest that the decreasing part of the fluorescence dip in
      FI of Trebouxia-lichens reflects the activation of ferredoxin-NADP(+)
      oxidoreductase or Mehler-peroxidase reaction leading to the fast reoxidation of
      electron carriers in thylakoid membranes. The increasing part of the dip probably
      reflects a transient reduction of plastoquinone (PQ) pool that is not associated
      with cyclic electron flow around PSI. Possible causes of this MV-insensitive PQ
      reduction are discussed.

PMID- 16403433
TI  - A 43 kDa protein from the herb Cajanus indicus L. protects thioacetamide induced
      cytotoxicity in hepatocytes.
AB  - The aim of this study was to investigate the role of a hepatoprotective protein
      isolated from the herb Cajanus indicus L. on thioacetamide (TAA) induced toxicity
      in isolated mouse hepatocytes. In vitro cell viability, lactate dehydrogenase
      (LDH), alanine aminotransferase (ALT) and total protein leakage were measured as
      the indicator of cell damage. The amount of glutathione (GSH) and lipid
      peroxidation were also measured to determine the oxidative status of the cells.
      The reduced cell viability in TAA treated hepatocytes was almost completely
      recovered upon protein treatment. LDH, ALT and total protein secretion outside
      the cells after TAA treatment confirmed the cell membrane damage. Incubation of
      hepatocytes with the protein prior to TAA administration significantly prevented
      the cell membrane damage as revealed from less LDH, ALT and total protein
      leakage. TAA depleted endogenous antioxidant GSH and increased membrane lipid
      peroxidation in hepatocytes. The protein had very prominent effect in altering
      the GSH level and lipid peroxidation. The protein exhibited all these
      cytoprotective effects in a dose-dependent manner. Besides, measurement of DPPH
      radical scavenging activity showed that the protein could scavenge free radicals.
      In addition, the protein resisted TAA induced alterations of various effects when
      applied in combination with TAA. The cytoprotective activity of the protein was
      found to be comparable with alpha-tocopherol, a well-known antioxidant. Results
      suggest that the protein from C. indicus can act as a hepatoprotector and primary
      antioxidant against TAA-induced cytotoxicity in mouse hepatocytes.

PMID- 16403434
TI  - Adiponectin as a growth inhibitor in prostate cancer cells.
AB  - Prostate cancer is associated with obesity. However, the molecular basis of this
      association is not well known. Adiponectin is a major adipose cytokine that
      decreases in circulation in obesity and ameliorates obesity. Here, we identify
      adiponectin as a novel inhibitor in prostate cancer cell growth. Adiponectin
      occurs in non-proteolytic (full-length adiponectin: f-adiponectin) and
      proteolytic (globular adiponectin) forms in various oligomeric states (trimer,
      hexamer, and high molecular weight complex). The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide assay demonstrates that f-adiponectin inhibits
      prostate cancer cell growth drastically at subphysiological concentrations.
      Furthermore, velocity sedimentation analysis shows that the high molecular weight
      complex of f-adiponectin is the inhibitory form. Moreover, f-adiponectin
      suppresses leptin- and/or insulin-like growth factor-I (IGF-I)-stimulated,
      androgen-independent DU145 cell growth, and dihydrotestosterone-stimulated,
      androgen-dependent LNCaP-FGC cell growth. In addition, f-adiponectin enhances
      doxorubicin inhibition of prostate cancer cell growth. Therefore, f-adiponectin
      is a molecular mediator between prostate cancer and obesity, and may be
      therapeutic to prostate cancer.

PMID- 16403435
TI  - Mn,Cd-metallothionein-2: a room temperature magnetic protein.
AB  - Naturally occurring metallothionein (MT) is a metal binding protein, which binds
      to seven Zn2+ through 20 conserved cysteines and forms two metal binding clusters
      with a Zinc-Blende structure. We demonstrate that the MT, when substituting the
      Zn2+ ions by Mn2+ and Cd2+, exhibits magnetic hysteresis loop observable by SQUID
      from 10 to 330 K. The magnetic moment may have originated from the bridging
      effect of the sulfur atoms between the metal ions that leads to the alignment of
      the electron spins of the Mn2+ ions inside the clusters. The protein backbone may
      restrain the net spin moment of Mn2+ ions from thermal fluctuation. The modified
      magnetic-metallothionein is a novel approach to creating molecular magnets with
      operating temperatures up to 330 K.

PMID- 16403436
TI  - Depression of proteasome activities during the progression of cardiac dysfunction
      in pressure-overloaded heart of mice.
AB  - The ubiquitin-proteasome system contributes to regulation of apoptosis degrading
      apoptosis-regulatory proteins. Marked accumulation of ubiquitinated proteins in
      cardiomyocytes of human failing hearts suggested impaired ubiquitin-proteasome
      system in heart failure. Since cardiomyocyte apoptosis contributes to the
      progression of cardiac dysfunction in pressure-overloaded hearts, we investigated
      the role of ubiquitin-proteasome system in such conditions. We found that
      proteasome activities already depressed before the onset of cardiac dysfunction
      in pressure-overloaded hearts of mice. Cardiomyocyte apoptosis was observed along
      with depression of proteasome activities and elevation of
      proapoptotic/antiapoptotic protein ratio in failing hearts. In cultured
      cardiomyocytes, pharmacological inhibition of proteasome accumulated proapoptotic
      proteins such as p53 and Bax. Gene silencing of these proapoptotic proteins by
      RNA interference prevented the accumulation of respective proteins and attenuated
      cardiomyocyte apoptosis induced by proteasome inhibition. We conclude that
      depression of proteasome activities contributes to cardiac dysfunction resulting
      from cardiomyocyte apoptosis through accumulation of proapoptotic proteins by
      impaired degradation.

PMID- 16403437
TI  - Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed
      with high fat diet.
AB  - The present study was performed to examine a role of adipose differentiation
      related protein (ADRP) in the process of liver steatosis. Immunohistochemical
      findings indicated that ADRP expression is increased in the hepatocytes in
      patients with fatty liver when compared with normal liver. ADRP expression is
      localized in the surface of lipid droplets in the hepatocytes. Increased
      expression of ADRP mRNA and protein was similarly observed in fatty liver in
      ob/ob mice and the liver steatosis induced by high fat diet in mice. The up
      regulation of ADRP mRNA and protein in the liver by high fat diet was identified
      in the surface of lipid droplets in a time-dependent manner. Recent studies
      demonstrated that up-regulation of PPARgamma in the hepatocytes is deeply
      involved in liver steatosis. To clarify whether ADRP expression is increased by
      PPARgamma activation in hepatocytes, we examined the effect of a PPARgamma
      ligand, troglitazone, on ADRP mRNA expression in HepG2 cells. ADRP mRNA
      expression was increased by troglitazone in dose- and time-dependent manners. All
      these results suggest that ADRP is up-regulated in liver steatosis in human and
      mice, and that high fat diet increases expression of ADRP through PPARgamma
      activation, followed by induction of liver steatosis.

PMID- 16403438
TI  - The protein kinase A inhibitor, H-89, directly inhibits KATP and Kir channels in
      rabbit coronary arterial smooth muscle cells.
AB  - The effects of the protein kinase A (PKA) inhibitor H-89 on ATP-sensitive K+
      (KATP) and inward rectifier K+ (Kir) currents were examined in rabbit coronary
      arterial smooth muscle cells using the patch clamp technique. The H-89, in a dose
      dependent manner, inhibited KATP and Kir currents with apparent Kd values of
      1.19+/-0.18 and 3.78+/-0.37 microM, respectively. H-85, which is considered as an
      inactive form of H-89, inhibited KATP and Kir currents, similar to the result of
      H-89. KATP and Kir currents were not affected by either Rp-8-CPT-cAMPs, which is
      a membrane-permeable selective PKA inhibitor, or KT 5720, which is also known as
      a PKA inhibitor. Also, these two drugs did not significantly alter the effects of
      H-89 on the KATP and Kir currents. These results suggest that H-89 directly
      inhibits the KATP and Kir currents of rabbit coronary arterial smooth muscle
      cells independently of PKA inhibition.

PMID- 16403439
TI  - Chemical synthesis and structure elucidation of bovine kappa-casein (1-44).
AB  - The caseins (alphas1, alphas2, beta, and kappa) are phosphoproteins present in
      bovine milk that have been studied for over a century and whose structures remain
      obscure. Here we describe the chemical synthesis and structure elucidation of the
      N-terminal segment (1-44) of bovine kappa-casein, the protein which maintains the
      micellar structure of the caseins. kappa-Casein (1-44) was synthesised by highly
      optimised Boc solid-phase peptide chemistry and characterised by mass
      spectrometry. Structure elucidation was carried out by circular dichroism and
      nuclear magnetic resonance spectroscopy. CD analysis demonstrated that the
      segment was ill defined in aqueous medium but in 30% trifluoroethanol it
      exhibited considerable helical structure. Further, NMR analysis showed the
      presence of a helical segment containing 26 residues which extends from Pro8 to
      Arg34. This is the first report which demonstrates extensive secondary structure
      within the casein class of proteins.

PMID- 16403440
TI  - Disordered osteoclast formation in RAGE-deficient mouse establishes an essential
      role for RAGE in diabetes related bone loss.
AB  - The mechanisms underlying diabetes-mediated bone loss are not well defined. It
      has been reported that the advanced glycation endproducts (AGEs) and receptor for
      AGEs (RAGEs) are involved in diabetic complications. Here, mice deficient in RAGE
      were used as a model for investigating the effects of RAGE on bone mass. We found
      that RAGE-/- mice have a significantly increased bone mass and bone biomechanical
      strength and a decreased number of osteoclasts compared to wild-type mice. The
      serum levels of IL-6 and bone breakdown marker pyridinoline were significantly
      decreased in RAGE-/- mice. RAGE-/- mice maintain bone mass following ovariectomy,
      whereas wild-type mice lose bone mass. Furthermore, osteoclast-like cells do
      express RAGE mRNA. Our data therefore indicate that RAGE serves as a positive
      factor to regulate the osteoclast formation, directly implicates a role for RAGE
      in diabetes-promoted bone destruction, and documents that the AGE-RAGE
      interaction may account for diabetes associated bone loss.

PMID- 16403441
TI  - Targeted delivery of antibodies through the blood-brain barrier by MRI-guided
      focused ultrasound.
AB  - The blood-brain barrier (BBB) is a persistent obstacle for the local delivery of
      macromolecular therapeutic agents to the central nervous system (CNS). Many drugs
      that show potential for treating CNS diseases cannot cross the BBB and there is a
      need for a non-invasive targeted drug delivery method that allows local therapy
      of the CNS using larger molecules. We developed a non-invasive technique that
      allows the image-guided delivery of antibody across the BBB into the murine CNS.
      Here, we demonstrate that subsequent to MRI-targeted focused ultrasound induced
      disruption of BBB, intravenously administered dopamine D(4) receptor-targeting
      antibody crossed the BBB and recognized its antigens. Using MRI, we were able to
      monitor the extent of BBB disruption. This novel technology should be useful in
      delivering macromolecular therapeutic or diagnostic agents to the CNS for the
      treatment of various CNS disorders.

PMID- 16403442
TI  - Dietary cholesterol and differential monocyte chemoattractant protein-1 gene
      expression in aorta and liver of apo E-deficient mice.
AB  - In humans, hypercholesterolemia, steatohepatitis, and risk for arteriosclerosis
      are associated. Apolipoprotein E-deficient mice, a widely used animal model, show
      both arteriosclerosis and steatohepatitis in response to high-fat and cholesterol
      diets. We have found a relationship between these conditions and a higher mRNA
      aortic and hepatic monocyte chemoattractant protein-1 (mcp-1) gene expression.
      Both tissues respond in a similar way when dietary cholesterol is provided for a
      few weeks but differently if the conditions persist for a protracted period of
      time. After 8 months of treatment, the mcp-1 gene expression in the aorta
      continues increasing but in the liver decreases. This coincides with a
      significant increase in hepatic ppar-delta anti-inflammatory gene expression.
      Apparently, the arterial wall cannot prevent the deleterious effects of higher
      mcp-1 expression by increasing ppar-delta gene expression and the lesion
      progress. However, in the liver, the activation of anti-inflammatory genes may
      reduce the hepatic mcp-1 expression which significantly decreases the
      inflammatory response. This differential inflammatory gene expression in aorta
      and liver may support the idea that anti-inflammatory transcription factors are
      involved in the response to diet and inflammation. Therefore, the use of
      cholesterol-enriched diets should be carefully considered in the apolipoprotein E
      deficient mice because they may trigger different stimuli and seriously hinder
      the interpretation of possible findings.

PMID- 16403443
TI  - Genetic characterization of CHO production host DG44 and derivative recombinant
      cell lines.
AB  - The dihydrofolate reductase-deficient Chinese hamster ovary (CHO) cell line DG44
      is the dominant mammalian host for recombinant protein manufacturing, in large
      part because of the availability of a well-characterized genetic selection and
      amplification system. However, this cell line has not been studied at the
      cytogenetic level. Here, the first detailed karyotype analysis of DG44 and
      several recombinant derivative cell lines is described. In contrast to the 22
      chromosomes in diploid Chinese hamster cells, DG44 has 20 chromosomes, only seven
      of which are normal. In addition, four Z group chromosomes, seven derivative
      chromosomes, and 2 marker chromosomes were identified. For all but one of the 16
      DG44-derived recombinant cell lines analyzed, a single integration site was
      detected by fluorescence in situ hybridization regardless of the gene delivery
      method (calcium phosphate-DNA coprecipitation or microinjection), the topology of
      the DNA (circular or linear), or the integrated plasmid copy number (between 1
      and 51). Chromosomal aberrations, observed in more than half of the cell lines
      studied, were mostly unbalanced with examples of aneuploidy, deletions, and
      complex rearrangements. The results demonstrate that chromosomal aberrations are
      frequently associated with the establishment of recombinant CHO DG44 cell lines.
      Noteworthy, there was no direct correlation between the stability of the genome
      and the stability of recombinant protein expression.

PMID- 16403444
TI  - mRNA transfection of dendritic cells: synergistic effect of ARCA mRNA capping
      with Poly(A) chains in cis and in trans for a high protein expression level.
AB  - The occurrence of translation mechanism in the cytosol offers advantages to mRNA
      transfer over DNA-based transfection in non-dividing cells. Here, we sought to
      optimize mRNA constructs allowing a high level of protein upon lipofection. We
      found that luciferase into mouse dendritic cells (JAWSII cells) was approximately
      20-fold higher when the luciferase mRNA was capped with 3'-O-methyl-m7(5')Gppp5'G
      (anti-reverse cap analogue; ARCA) than with m7(5')Gppp5'G (CAP). Adding a Poly(A)
      tail of 100 instead of 64 adenosines in cis increased by approximately 35-fold
      more the protein level. Finally, ARCA-Luc-mRNA-A100 construct was 700-fold better
      efficient than the CAP-Luc-mRNA-A64 one. Moreover, co-transfection with free
      Poly(A) chains in trans enhanced by 100% the luciferase level. The efficiency of
      ARCA-mRNA-A100 construct was validated in immature and mature human CD34-derived
      dendritic cells. Such mRNA construct was also successful to obtain high level of
      MART-1 tumor antigen.

PMID- 16403445
TI  - Heat-regulated production and secretion of insulin from a human artificial
      chromosome vector.
AB  - Human artificial chromosomes (HACs) behave as independent minichromosomes and are
      potentially useful as a way to achieve safe, long-term expression of a transgene.
      In this study, we sought to elucidate the potential of HAC vectors carrying the
      human proinsulin transgene for gene therapy of insulin-dependent diabetes
      mellitus (IDDM) using non-beta-cells as a host for the vector. To facilitate the
      production of mature insulin in non-beta-cells and to safely regulate the level
      of transgene expression, we introduced furin-cleavable sites into the proinsulin
      coding region and utilized the heat shock protein 70 (Hsp70) promoter. We used
      Cre-loxP-mediated recombination to introduce the gene cassettes onto
      21DeltapqHAC, a HAC vector whose structure is completely defined, present in
      human fibrosarcoma HT1080 cells. We observed long-term expression and stable
      retention of the transgene without aberrant translocation of the HAC constructs.
      As expected, the Hsp70 promoter allowed us to regulate gene expression with
      temperature, and the production and secretion of intermediates of mature insulin
      were made possible by the furin-cleavable sites we had introduced into
      proinsulin. This study can be an initial step on the application of HAC vectors
      on the gene delivery to non-beta-cells, which might provide a direction for
      future treatment for diabetes.

PMID- 16403446
TI  - Arabidopsis AtIscA-I is affected by deficiency of Fe-S cluster biosynthetic
      scaffold AtCnfU-V.
AB  - IscA has been proposed to be a scaffold protein of the iron-sulfur cluster
      biosynthetic machinery. We have identified the IscA homolog to be localized to
      plastids, termed AtIscA-I, in Arabidopsis thaliana. The AtIscA-I protein was
      apparently constitutively expressed in all tissues analyzed in Arabidopsis. The
      AtIscA-I protein exists in the stroma as a soluble protein which tends to form a
      homo-dimer and can host a [2Fe-2S]-like cluster. Complete loss of the protein
      from plastids did not cause any significant defect either in normal plant growth
      or in biogenesis of major iron-sulfur proteins, indicating this protein is not
      essential or redundant for these functions. In contrast, loss of one of the three
      plastid-localized CnfU scaffold proteins, AtCnfU-V, caused significant reduction
      in the level of AtIscA-I. These data suggest that efficient biogenesis of AtIscA
      I scaffold requires function of another essential scaffold protein CnfU.

PMID- 16403447
TI  - Crystal structure of PilF: functional implication in the type 4 pilus biogenesis
      in Pseudomonas aeruginosa.
AB  - PilF is a requisite protein involved in the type 4 pilus biogenesis system from
      the Gram-negative human pathogenic bacteria, Pseudomonas aeruginosa. We
      determined the PilF structure at a 2.2A resolution; this includes six tandem
      tetratrico peptide repeat (TPR) units forming right-handed superhelix. PilF
      structure was similar to the heat shock protein organizing protein, which
      interacts with the C-terminal peptide of Hsp90 and Hsp70 via a concave Asn ladder
      in the inner groove of TPR superhelix. After simulated screening, the C-terminal
      pentapeptides of PilG, PilU, PilY, and PilZ proved to be a likely candidate
      binding to PilF, which are ones of 25 necessary components involved in the type 4
      pilus biogenesis system. We proposed that PilF would be critical as a bridgehead
      in protein-protein interaction and thereby, PilF may bind a necessary molecule in
      type 4 pilus biogenesis system such as PilG, PilU, PilY, and PilZ.

PMID- 16403448
TI  - Expression and characterization of a brain-specific protein kinase BSK146 from
      zebrafish.
AB  - We have previously identified a novel protein kinase, pk146, in the brain of
      Tetraodon. In the present study, we cloned the homologous protein kinase gene
      encoding a protein of 385 amino acid residues from zebrafish. The overall amino
      acid sequence and the kinase domain of zebrafish BSK146 shows 48% and 69%
      identity to that of rat sbk, a SH3-containing serine/threonine protein kinase. By
      whole-mount in situ hybridization and RT-PCR, the expression of bsk146 mRNA was
      mainly in the brain. To explore the in vivo function of BSK146 during zebrafish
      development, we used morpholino knockdown approach and found that BSK146
      morphants displayed enlarged hindbrain ventricle and smaller eyes. Whole-mount in
      situ hybridization was further performed to analyze the brain defects in BSK146
      MO-injected embryos. The expression of brain-specific markers, such as otx2,
      pax2.1, and krox20, was found normal in morphant embryos at 24hpf, while
      expression of pax2.1 exerted changes in midbrain-hindbrain boundary and hindbrain
      in morphant embryos at 48hpf. These data suggest that BSK146 may play an
      important role in later ventricle expansion in zebrafish brain development.
      Although the recombinant BSK146 protein produced in insect cells was active and
      could phosphorylate both histone H1 and histone 2B, the endogenous substrate of
      BSK146 in the embryonic brain of zebrafish is not clear at the present time and
      needs further investigation.

PMID- 16403449
TI  - Analysis of the human MutLalpha.MutSalpha complex.
AB  - Human DNA mismatch repair is initiated by MutSalpha which ATP-dependently
      recruits MutLalpha. Analysis of this complex is difficult due to its transient
      and dynamic nature. We have optimized conditions for investigation of
      MutLalpha.MutSalpha complexes using a DNA pulldown assay. Non-specific DNA end
      binding, which frequently interfered with analysis of the interaction, did not
      occur under the applied conditions. MutSalpha had significantly higher affinity
      to DNA mispairs, but its interaction with MutLalpha did not require a mismatch.
      Complex formation was best supported by low magnesium concentration and low
      temperature at physiological pH and salt concentration. Complex formation was
      delayed by the slowly hydrolyzable ATP analog ATPgammaS, undetectable with the
      non-hydrolyzable analog AMP-PNP, and occurred weakly with a combination of AMP
      PNP and ADP, confirming that hydrolysis was required. The described conditions
      likely capture an intermediate of the repair reaction which has bound ATP and ADP
      in the two nucleotide-binding sites of MutSalpha.

PMID- 16403450
TI  - Determining the 3D structure of human ASC2 protein involved in apoptosis and
      inflammation.
AB  - ASC2 structure has been well defined by 1141 NOE experimental restraints. The
      model consists of five alpha helices. alpha-Helices are connected by short random
      structure loops. The sole exception is the loop connecting helices 2 and 3, which
      has a 20-residue length. Folding generally agrees with the folding of recently
      published death domain structures in which alpha-helix structures have been
      reported. In spite of structural similarity, amino acid sequence homology with
      the most similar protein (ASC1) is just 64%. DD, DED, and CASP protein structures
      present six helices along their sequences; ASC2 presents 5 well-defined helices
      due to long distance restraints. However, a helical fragment was observed between
      amino acids 38 and 42 (representing helix 3) in the death domains when
      constructing the model.

PMID- 16403452
TI  - Function and subcellular location of Ro52beta.
AB  - Autoantigen Ro52alpha was recently identified as an E3 ubiquitin ligase. Its
      splicing variant Ro52beta, which lacks a leucine zipper, has not been
      characterized yet. We therefore characterized Ro52beta in contrast to Ro52alpha.
      Our biochemical assays revealed that both Ro52alpha and Ro52beta function as E3
      ubiquitin ligases and self-ubiquitinate in cooperation with UbcH5B in vitro. In
      addition, both Ro52alpha and Ro52beta are ubiquitinated when overexpressed with
      ubiquitin in HEK293T cells, suggesting that both function as E3 ligases and self
      ubiquitinate in vivo. However, cytological studies revealed that Ro52alpha mainly
      localizes to the cytoplasmic rod-like structures, whereas Ro52beta diffusely
      localizes to both the cytoplasm and the nucleus. Since the leucine zipper plays a
      role in the homodimerization and heterodimerization of Ro52alpha, the
      dimerization might be required for the localization of Ro52alpha to the rod-like
      structures. On the basis of these results, Ro52alpha and Ro52beta appear to
      ubiquitinate their particular substrates at different locations.

PMID- 16403451
TI  - A novel isoform of delta-sarcoglycan is localized at the sarcoplasmic reticulum
      of mouse skeletal muscle.
AB  - The sarcoglycan-sarcospan complex (alpha-, beta-, gamma-, delta-, epsilon-, and
      zeta-SG-SSPN), a component of the dystrophin-associated glycoprotein complex
      (DAGC), is located at the sarcolemma of muscle fibers where it contributes to
      maintain cell integrity during contraction-relaxation cycles; gamma- and delta-SG
      are also expressed in the sarcoplasmic reticulum (SR). In this study, we report
      the identification of a novel isoform of murine delta-SG produced by alternative
      splicing that we named delta-SG3. This isoform is present at transcript level in
      several tissues, with its highest expression in skeletal and cardiac muscle. The
      delta-SG3 protein lacks the last 122 amino acids at the C-terminal, which are
      replaced by 10 new amino acids (EGFLNMQLAG). Interestingly, double
      immunofluorescence analysis for delta-SG3 and the dihydropyridine receptor (DHPR)
      shows a close localization of these two proteins. We propose the subcellular
      distribution of this novel delta-SG3 isoform at the SR and its involvement in
      intracellular calcium concentration regulation.

PMID- 16403453
TI  - Purification by p-aminobenzoic acid (PABA)-affinity chromatography and the
      functional reconstitution of the nateglinide/H+ cotransport system in the rat
      intestinal brush-border membrane.
AB  - (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) is a
      novel oral hypoglycemic agent possessing a peptide-type bond and a carboxyl group
      in its structure. Recently, we have shown that nateglinide transport occurs via
      the ceftibuten/H+ cotransport system, which is distinct from PepT1, and that the
      fluorescein/H+ cotransport system is involved in the uptake of nateglinide. The
      aim of this study was to characterize the functional properties of the intestinal
      nateglinide transporter. In the first part of this study, we demonstrated that
      the ceftibuten/H+ cotransport system is identical to the fluorescein/H+
      cotransport system. We succeeded in purification of the nateglinide transporter
      from brush-border membranes of the rat small intestine using p-aminobenzoic acid
      (PABA)-affinity chromatography. We then investigated the functional properties of
      the nateglinide transporter using proteoliposomes prepared from the PABA-affinity
      chromatography elute. We demonstrated that nateglinide, ceftibuten, and
      fluorescein are transported by the same transporter in the intestine.

PMID- 16403454
TI  - The intertidal copepod Tigriopus japonicus small heat shock protein 20 gene
      (Hsp20) enhances thermotolerance of transformed Escherichia coli.
AB  - To understand the role of the Tigriopus japonicus Hsp20 gene, we isolated this
      gene from a whole body cDNA library and found two heat shock factor elements at
      the 5'-UTR. The transformed bacteria containing Tigriopus Hsp20 showed
      thermotolerance against heat shock (54 degrees C) with different ranges of time.
      The Tigriopus Hsp20 gene is comprised of 174 amino acid residues and shows
      similarity to Caenorhabditis elegans (27% identity), silkworm (24.1% identity),
      moth (24.1% identity), Mexican tetra (19.5% identity), zebrafish (19.5%
      identity), and spiny dogfish (17.2% identity) genes, but shows more similarity in
      the C-terminal region that contains an alpha-crystallin domain. Protein motifs
      such as an N-glycosylation site (67-70 NKSE) and a casein kinase II
      phosphorylation site were found in Tigriopus Hsp20. The genomic structure of the
      Tigriopus Hsp20 gene did not contain introns. To characterize the biochemical
      characteristics of the Tigriopus Hsp20 protein, we expressed Tigriopus Hsp20 in
      Escherichia coli and purified the soluble protein via 6x His-tag chromatography.
      To analyze the gene expression of Tigriopus Hsp20 against environmental stresses
      (e.g., water temperature and salinity), we performed a semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR). On exposure to different
      salinities, significant change in the expression of Tigriopus Hsp20 was not
      observed. However, upon heat shock (30 degrees C), Tigriopus Hsp20 expression was
      significantly increased, but in the case of cold shock (4 or 10 degrees C),
      expression was likely downregulated. These findings provide a better
      understanding of cellular protection mechanisms against environmental stress such
      as heat shock.

PMID- 16403455
TI  - Blocking of G1/S transition and cell death in the regenerating liver of Hepatitis
      B virus X protein transgenic mice.
AB  - The Hepatitis B virus X (HBx) protein has been strongly implicated in the
      carcinogenesis of hepatocellular carcinoma (HCC). However, effects of the HBx
      protein on cell proliferation and cell death are controversial. This study
      investigates the effects of the HBx protein on liver regeneration in two
      independent lines of HBx transgenic mice, which developed HCC at around 14 to 16
      months of age. High mortality, lower liver mass restoration, and impaired liver
      regeneration were found in the HBx transgenic mice post-hepatectomy. The levels
      of alanine aminotransferase and alpha-fetoprotein detected post-hepatectomy
      increased significantly in the HBx transgenic livers, indicating that they were
      more susceptible to damage during the regenerative process. Prolonged activation
      of the immediate-early genes in the HBx transgenic livers suggested that the HBx
      protein creates a strong effect by promoting the transition of the quiescent
      hepatocytes from G0 to G1 phase. However, impaired DNA synthesis and mitosis, as
      well as inhibited activation of G1, S, and G2/M markers, were detected. These
      results indicated that HBx protein exerted strong growth arrest on hepatocytes
      and imbalanced cell-cycle progression resulting in the abnormal cell death; this
      was accompanied by severe fat accumulation and impaired glycogen storage in the
      HBx transgenic livers. In conclusion, this study provides the first physiological
      evidence that HBx protein blocks G1/S transition of the hepatocyte cell-cycle
      progression and causes both a failure of liver functionality and cell death in
      the regenerating liver of the HBx transgenic mice.

PMID- 16403456
TI  - Chronic CO levels have [corrected] a beneficial effect on vascular relaxation in
      diabetes.
AB  - Heme oxygenase (HO) has been shown to provide cytoprotection to the vascular
      system in diabetes. Isolated femoral arteries from diabetic rats treated with
      cobalt protoporphyrin (CoPP) exhibited increased relaxation to acetylcholine
      (ACh), which was markedly decreased in control diabetic rats. In control rats
      treated with either CoPP or with CO releasing molecules-3 (CORM-3), but not in
      rats treated with biliverdin, we observed an increased dilatory response to ACh.
      The inhibition of guanylyl-cyclase (GC) with 1H-[1,2,4]Oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ) caused a contractile response to ACh in control rats and
      in biliverdin-treated rats, while in rats treated with CoPP and CORM-3, the ACh
      dilatory effect was only decreased. Moreover, the inhibition of HO with chromium
      mesoporphyrin did not change the response to ACh in rats treated with CoPP,
      suggesting that the improving effect of overproduction of CO on vascular
      reactivity is due to a decrease in iNOS and the beneficial effect on vascular
      function.

PMID- 16403457
TI  - Mesenchymal progenitor cells derived from chorionic villi of human placenta for
      cartilage tissue engineering.
AB  - Human mesenchymal stem cells are currently being studied extensively because of
      their capability for self-renewal and differentiation to various connective
      tissues, which makes them attractive as cell sources for regenerative medicine.
      Herein we report the isolation of human placenta-derived mesenchymal cells
      (hPDMCs) that have the potential to differentiate into various lineages to
      explore the possibility of using these cells for regeneration of cartilage. We
      first evaluated the chondrogenesis of hPDMCs in vitro and then embedded the
      hPDMCs into an atelocollagen gel to make a cartilage-like tissue with
      chondrogenic induction media. For in vivo assay, preinduced hPDMCs embedded in
      collagen sponges were subcutaneously implanted into nude mice and also into nude
      rats with osteochondral defect. The results of these in vivo and in vitro studies
      suggested that hPDMCs can be one of the possible allogeneic cell sources for
      tissue engineering of cartilage.

PMID- 16403458
TI  - Transposome mutagenesis of an integral membrane transporter in Corynebacterium
      matruchotii.
AB  - A transposon-5 insertion library of Corynebacterium matruchotii ATCC14266 was
      generated and screened for mutants with altered corynomycolic acid content. One
      of these designated 319 mutants showed an interruption of a gene encoding an
      integral membrane protein. MALDI mass spectra of trehalose monocorynomycolate
      (TMCM), trehalose dicorynomycolate, and methyl corynomycolates derived from cell
      wall arabinogalactan-corynomycolate showed that these lipids from the mutant
      contained a lower amount of short-chain (C24 to C34) and much greater amount of
      long-chain (primarily C(36:2)) corynomycolic acids than the wild type. An
      analysis of mRNA demonstrated that the integral membrane protein and ATP-binding
      cassette transporter are transcriptionally coupled. These results suggested that
      the proteins/enzymes encoded by the membrane transporter gene locus preferably
      move short-chain corynomycolic acids from the cytoplasm across the membrane
      bilayer to the periplasmic space where the synthesis of TMCM is thought to occur.
      This is the first evidence linking corynomycolic acid to a transporter gene
      locus.

PMID- 16403459
TI  - Rapid modulation of Ca2+ uptake in human jejunal enterocytes.
AB  - The active metabolite of D vitamin, 1,25(OH)2D3, has been suggested to promote
      acute uptake of calcium through the intestinal lining in cell lines and murine
      models. In this study, the effects of D vitamin on the cytoplasmic Ca2+ of single
      human jejunal enterocytes, obtained with LOC-I-GUT technique, was analyzed in
      vivo in a fluorometric system using fura-2 as the Ca2+-sensing probe. Vitamin
      promoted acute Ca2+ influx exhibited dual kinetics, indicating initial release
      from intracellular Ca2+ pools and fast entry from the extracellular space.
      Furthermore, providing a chemical clamp of membrane potential close to 0 mV did
      not activate voltage-sensitive calcium channels in the cellular membrane, neither
      was the hormone-induced Ca2+ influx affected by verapamil. This advocates that
      voltage-operated channels like L-type Ca2+ channels do not participate in the
      process of Ca2+ uptake. In fact, the existence of calcium-release-activated
      calcium channels (I(CRAC)) was implied by the findings that irreversible
      depletion of intracellular Ca2+ stores by thapsigargin promoted Ca2+ entry. In
      the thapsigargin-treated enterocytes, D vitamin lost its ability to promote
      calcium entry indicating an important role for intracellular store-operated Ca2+
      stores in the acute effects of 1,25(OH)2D3.

PMID- 16403460
TI  - Identification of DLK1 variants in pituitary- and neuroendocrine tumors.
AB  - In a gene chip analysis of common pituitary tumor types, one of the genes with
      the most impressive tissue-specific expression regulation was delta-like 1
      (DLK1), which was strongly expressed in GH-secreting (GH-S) pituitary tumors. In
      addition to pituitary adenomas, various endocrine tumors were subjected to real
      time-quantitative PCR revealing high expression of DLK1 in normal pituitary
      tissue, in GH-S-, in one prolactin-secreting pituitary adenoma and in
      pheochromocytomas. Additionally, three DLK1 gene-derived subvariants were
      identified. The first, lacking 204 bp--coding for epidermal growth factor-like
      domain 6 and parts of the juxtamembrane region--was named Secredeltin. In the
      other two splice variants (named Brevideltin and Brevideltinin), a stop codon is
      introduced due to a frame-shift, leading to truncated proteins of 204 and 213
      aas, respectively.

PMID- 16403461
TI  - Insulin-like growth factor-I-coupled mitogenic signaling in primary cultured
      human skeletal muscle cells and in C2C12 myoblasts. A central role of protein
      kinase Cdelta.
AB  - In this study, we have investigated the effects of insulin-like growth factor-I
      (IGF-I) on cellular responses of primary human skeletal muscle cells and mouse
      C2C12 myoblasts. In human muscle, IGF-I stimulated proliferation and fusion of
      the cells and the expression of the differentiation marker desmin. These effects
      were completely inhibited by Rottlerin, the inhibitor of the protein kinase C
      (PKC)delta, but were not affected by the inhibition of the mitogen-activated
      protein kinase (MAPK) or the phosphatidylinositide 3-kinase (PI-3K) pathways.
      Furthermore, IGF-I initiated the selective translocation of PKCdelta to the
      nucleus. In C2C12 myoblasts, the growth-promoting effects of IGF-I were abrogated
      by inhibition of PKCdelta, but not by the inhibition of the PI-3K system.
      However, in contrast to the human data, the MAPK inhibitor PD098059 partially
      (yet significantly) also inhibited the action of IGF-I and, furthermore, IGF-I
      induced phosphorylation of the MAPK Erk-1/2. In addition, overexpression of
      constitutively active form of PKCdelta in C2C12 cells fully mimicked, whereas
      overexpression of kinase inactive mutant of the isoform prevented the action of
      IGF-I. Finally, the inhibition of PKCdelta suspended the IGF-I-induced
      phosphorylation of Erk-1/2 and, moreover, the inhibition of the MAPK pathway
      partially (yet significantly) inhibited the accelerated growth of C2C12 cells
      overexpressing PKCdelta. Taken together, these results demonstrate a novel,
      central and exclusive involvement of PKCdelta in mediating the action of IGF-I on
      human skeletal muscle cells, with an additional yet PKCdelta-dependent
      contribution of the MAPK pathway on C2C12 myoblasts.

PMID- 16403462
TI  - Combined perception of emotion in pictures and musical sounds.
AB  - Evaluation of emotional scenes requires integration of information from different
      modality channels, most frequently from audition and vision. Neither the
      psychological nor neural basis of auditory-visual interactions during the
      processing of affect is well understood. In this study, possible interactions in
      affective processing were investigated via event-related potential (ERP)
      recordings during simultaneous presentation of affective pictures (from IAPS) and
      affectively sung notes that either matched or mismatched each other in valence.
      To examine the role of attention in multisensory affect-integration ERPs were
      recorded in two different rating tasks (voice affect rating, picture affect
      rating) as participants evaluated the affect communicated in one of the
      modalities, while that in the other modality was ignored. Both the behavioral and
      ERP data revealed some, although non-identical, patterns of cross-modal
      influences; modulation of the ERP-component P2 suggested a relatively early
      integration of affective information in the attended picture condition, though
      only for happy picture-voice pairs. In addition, congruent pairing of sad
      pictures and sad voice stimuli affected the late positive potential (LPP).
      Responses in the voice affect rating task were overall more likely to be
      modulated by the concomitant picture's affective valence than vice versa.

PMID- 16403463
TI  - Identification of first candidate genes for creativity: a pilot study.
AB  - Studies from behavioral genetics have demonstrated the high heritability of
      intelligence. However, the endeavor to detect the genes forming the molecular
      basis of intelligence has been rather unsuccessful until now. Pharmacological
      studies have demonstrated the influence of the dopaminergic (DA) and the
      serotonergic (5-HT) system on subcomponents of cognitive functioning, and first
      studies from molecular genetics have demonstrated that genes related to the DA
      metabolism are associated with mental abilities. However, candidate genes for
      creativity have not been identified so far. Therefore, the influence of the
      catechol-O-methyltransferase (locus: COMT VAL158MET) gene and the dopamine D2
      receptor gene (locus: DRD2 TAQ IA) on creativity was tested in addition to a
      serotonergic gene, TPH1 (locus: TPH-A779C), in a sample of N = 92 healthy
      Caucasian subjects while controlling for intelligence. Results showed that the
      DRD2 gene and the TPH gene were both associated with total creativity, explaining
      9% of the variance, while COMT was not related to creativity at all. With respect
      to the subcomponents, the A1+ allele of DRD2 was related to higher verbal
      creativity as compared to the A1- allele, and carriers of the A allele of TPH1
      showed significantly higher scores in figural and in numeric creativity,
      indicating that the two gene loci discriminate between higher cortical functions
      according to the organization of cognitive functions in the respective
      hemispheres.

PMID- 16403464
TI  - Focal ischemia induces expression of protease-activated receptor1 (PAR1) and PAR3
      on microglia and enhances PAR4 labeling in the penumbra.
AB  - Thrombin significantly influences neurodegenerative processes after ischemia. The
      current literature suggests that the effects are mediated via protease-activated
      receptors 1, 3 and 4 (PAR1, 3, 4). Therefore, we investigated with
      immunohistochemical methods whether focal cerebral ischemia altered the
      expression of PARs in the rodent brain. For this purpose, we used the model of
      endothelin-induced occlusion of the middle cerebral artery and the model of
      transcranial permanent occlusion of the middle cerebral artery in mice. In
      contrast to the exclusively neuronal staining in the brain parenchyma of naive
      animals, PAR1 and PAR3 occurred in addition on microglial cells in the penumbra
      after transient and after permanent focal ischemia. Although microglia activation
      could be detected for several weeks after the insult, PAR1 and PAR3 were
      traceable on microglia only 12 and 48 h after the insult, but not on day 7 post
      ischemia. PAR4 was expressed, both in naive and in ischemic animals, exclusively
      in neuronal cells. However, at the border zone and within the infarct area,
      enhanced immunohistochemical PAR4 signals were recognized. From our data, we
      conclude that PAR1 and PAR3 could be involved in thrombin-modulated initiation of
      post-ischemic inflammation and PAR4 may be associated with neuronal degeneration.

PMID- 16403465
TI  - Hemorrhage activates proopiomelanocortin neurons in the rat hypothalamus.
AB  - Severe blood loss lowers arterial pressure through a central mechanism that is
      thought to include opioid neurons. In this study, we investigated whether
      hemorrhage activates proopiomelanocortin (POMC) neurons by measuring Fos
      immunoreactivity and POMC mRNA levels in the medial basal hypothalamus.
      Hemorrhage (2.2 ml/100 g body weight over 20 min) increased the number of Fos
      immunoreactive neurons throughout the rostral-caudal extent of the arcuate
      nucleus, the retrochiasmatic area and the peri-arcuate region lateral to the
      arcuate nucleus where POMC neurons are located. Double label immunohistochemistry
      revealed that hemorrhage increased Fos expression by beta-endorphin
      immunoreactive neurons significantly. The proportion of beta-endorphin
      immunoreactive neurons that expressed Fos immunoreactivity increased
      approximately four-fold, from 11.7+/-1.4% in sham-operated control animals to
      42.0+/-5.2% in hemorrhaged animals. Hemorrhage also increased POMC mRNA levels in
      the medial basal hypothalamus significantly, consistent with the hypothesis that
      blood loss activates POMC neurons. To test whether activation of arcuate neurons
      contributes to the fall in arterial pressure evoked by hemorrhage, we inhibited
      neuronal activity in the caudal arcuate nucleus by microinjecting the local
      anesthetic lidocaine (2%; 0.1 or 0.3 microl) bilaterally 2 min before hemorrhage
      was initiated. Lidocaine injection inhibited hemorrhagic hypotension and
      bradycardia significantly although it did not influence arterial pressure or
      heart rate in non-hemorrhaged rats. These results demonstrate that hemorrhage
      activates POMC neurons and provide evidence that activation of neurons in the
      arcuate nucleus plays an important role in the hemodynamic response to
      hemorrhage.

PMID- 16403466
TI  - Activation of p38 mitogen-activated protein kinase in spinal microglia mediates
      morphine antinociceptive tolerance.
AB  - Compelling evidence has suggested that spinal glial cells were activated by
      chronic morphine treatment and involved in the development of morphine tolerance.
      However, the mechanisms of glial activation were still largely unknown in
      morphine tolerance. In present study, we investigated the role of p38 mitogen
      activated protein kinase (p38 MAPK) in the spinal cord in the development of
      chronic morphine antinociceptive tolerance. We found that intrathecal
      administration of morphine (15 microg) daily for 7 consecutive days significantly
      induced an increase in number of phospho-p38 (p-p38) immunoreactive cells in the
      spinal cord compared with chronic saline or acute morphine treated rats. Double
      immunofluorescence staining revealed that p-p38 immunoreactivity was exclusively
      restricted in the activated spinal microglia, not in astrocytes or neurons.
      Repeated intrathecal administration of 4-(4-fluorophenyl)-2-(4
      methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) (10 microg or 2
      microg), a specific p38 inhibitor, 30 min before each morphine injection for 7
      consecutive days significantly attenuated tolerance to morphine analgesia
      assessed by tail flick test. However, a single intrathecal administration of
      SB203580 (10 microg) did not antagonize the established tolerance to morphine
      analgesia. Taken together, these findings suggested that p38 MAPK activation in
      the spinal microglia was involved in the development of morphine antinociceptive
      tolerance. Inhibition of p38 MAPK by SB203580 in the spinal cord attenuated but
      not reversed the tolerance to morphine analgesia. The present study provides the
      first evidence that p38 activation in spinal microglia played an important role
      in the development of tolerance to morphine analgesia.

PMID- 16403467
TI  - Temporal resolution properties of human auditory cortex: reflections in the
      neuromagnetic auditory evoked M100 component.
AB  - Previous work has provided evidence for a brief, finite ( approximately 35 ms)
      temporal window of integration (TWI) in M100 formation, during which stimulus
      attributes are accumulated in processes leading to the M100 peak. Here, we
      investigate resolution within the TWI by recording responses to tones containing
      silent gaps (0-20 ms). Gaps were inserted in 1 kHz tones in 2 conditions: +10 ms
      post-onset (10 ms masker) wherein the masker and gap of longest duration (20 ms)
      were contained within the initial 35 ms of the stimulus and +40 ms (40 ms masker)
      wherein all gaps were inserted +40 ms post-onset. Tones were presented binaurally
      and responses sampled from both hemispheres in 12 adults using a twin 37-channel
      biomagnetometer (MAGNES-II, BTi, San Diego, CA). Results--10 ms masker: M100
      latency was prolonged and amplitude decreased as a function of gap duration, even
      with the shortest duration (2 ms) gap, indicating that integrative processes
      underlying M100 formation are sensitive to fine-grained discontinuities within a
      brief, finite TWI. Results--40 ms masker: M100 latency and amplitude were
      unaffected by gaps inserted at +40 ms, providing further evidence for an M100 TWI
      of <40 ms. CONCLUSION: within a brief integrative window in M100 formation,
      population-level responses are sensitive to discontinuities in sounds on a scale
      corresponding to psychophysical detection thresholds and minimum detectable gap
      thresholds in single unit recordings. Cumulatively, results provide evidence that
      M100 resolution for brief fluctuations in sounds reflects temporal acuity
      properties that are both intrinsic to the auditory system and critical to the
      accurate perception of speech.

PMID- 16403468
TI  - Selective temporal attention enhances the temporal resolution of visual
      perception: Evidence from a temporal order judgment task.
AB  - We investigated whether attending to a particular point in time affects temporal
      resolution in a task in which participants judged which of two visual stimuli had
      been presented first. The results showed that temporal resolution can be improved
      by attending to the relevant moment as indicated by the temporal cue. This novel
      finding is discussed in terms of the differential effects of spatial and temporal
      attention on temporal resolution.

PMID- 16403469
TI  - Evidence supporting a role for corticotropin-releasing factor type 2 (CRF2)
      receptors in the regulation of subpopulations of serotonergic neurons.
AB  - Corticotropin-releasing factor (CRF)-related peptides can modulate stress-related
      physiology and behavior. Some of these effects may be mediated via the CRF type 2
      (CRF2) receptor on serotonergic neurons in the dorsal raphe nucleus (DR). To
      determine if the CRF2 receptor agonist urocortin 2 (Ucn 2) increases c-Fos
      expression in rat DR serotonergic neurons via actions on CRF2 receptors, we gave
      intracerebroventricular (icv) injections of mouse Ucn 2 after icv injections of
      either saline or the CRF2 receptor antagonist antisauvagine-30 (ASV-30). Double
      immunostaining methods for c-Fos and tryptophan hydroxylase revealed that,
      consistent with previous studies, mouse Ucn 2 increased c-Fos expression in
      tryptophan hydroxylase immunostained neurons in the middle and caudal parts (
      8.18, -8.54, and -9.16 mm bregma) of the dorsal subdivision of the dorsal raphe
      nucleus 2 h after drug treatment. Pre-treatment with ASV-30 blocked these
      effects. Mouse Ucn 2 had no effect on c-Fos expression within the median raphe
      nucleus, consistent with the hypothesis that Ucn 2 has specific actions on an
      anatomically and functionally distinct subset of serotonergic neurons via
      activation of CRF2 receptors. These findings are also consistent with the
      hypothesis that Ucn 2, or another CRF-related neuropeptide acting at CRF2
      receptors, modulates physiological and behavioral responses to stress-related
      stimuli via actions on a specific subset of serotonergic neurons within the
      dorsal raphe nucleus.

PMID- 16403470
TI  - Expression of the monocarboxylate transporter MCT1 in the adult human brain
      cortex.
AB  - Distribution of the monocarboxylate transporter MCT1 has been investigated in the
      cortex of normal adult human brain. Similarly to the glucose transporter GLUT1 55
      kDa isoform, MCT1 was found to be strongly expressed on blood vessels in all
      cortical layers. In addition, laminar analysis revealed intense MCT1 expression
      in the neuropil of layer IV in primary auditory (AI) and visual (VI) areas, while
      this expression was more homogeneous in the non-primary auditory area STA. The
      cellular distribution shows that MCT1 is strongly expressed by glial cells often
      associated with blood vessels that were identified as astrocytes. The observed
      distribution of MCT1 supports the concept that, under certain circumstances,
      monocarboxylates could be provided as energy substrates to the adult human brain.
      Moreover, the distinct laminar pattern of MCT1 expression between primary and non
      primary cortical areas may reflect different types of neuronal activity requiring
      adequate supply of specific energy substrates.

PMID- 16403471
TI  - Dexamethasone induces cell death which may be blocked by NMDA receptor
      antagonists but is insensitive to Mg2+ in cerebellar granule neurons.
AB  - Since dexamethasone may elevate the Ca2+ influx through NMDA receptors, we have
      investigated mechanisms of dexamethasone toxicity in rat cerebellar granule
      neurons. Dexamethasone concentrations over 0.1 microM induced cell death that
      reached about 20% of the death induced by glutamate. Dexamethasone-induced cell
      death was reduced by more than 80% by the mineralocorticoid antagonist RU 28318
      or the NMDA receptor antagonists MK 801 and CGP 39551, whereas RU 28318 rescued
      only approximately 30% of cells treated with glutamate, indicating that
      dexamethasone requires NMDA receptors to induce acute neuronal toxicity and that
      a fraction of the neurons showed this toxicity. Mg2+ reduced the cell death
      induced by glutamate at potassium concentrations of 1 mM and 5 mM, but not at 25
      mM. In contrast, cell death induced by dexamethasone was not significantly
      reduced by Mg2+ in any of the potassium concentrations. Both glutamate and
      dexamethasone induced toxicity with translocation of the apoptosis inducer NGFI-B
      to the mitochondria seen after 30 min-2 h concomitant with activation of
      apoptosis inducing factor (AIF) and caspase-3. In conclusion, dexamethasone
      induces a rapid toxicity which is blocked by NMDA receptor antagonists other than
      Mg2+, and involves mitochondrial apoptosis inducer NGFI-B.

PMID- 16403472
TI  - Variations of dopamine, serotonin, and amino acid concentrations in Noda
      epileptic rat (NER) retina.
AB  - Noda epileptic rats (NER) exhibit frequent spontaneous tonic-clonic convulsions
      which represent a valuable model of human epilepsy. If implication of brain
      neurotransmitters was largely reported, little is known about retina. However, it
      has been reported that human epilepsy syndrome varies not only with the location
      of seizure foci but also according to rhythmic patterns, for which retina has a
      major role in the transmission of external light-dark cycle information. The
      purpose of this work was to evaluate dopamine (DA), DA metabolites, serotonin (5
      HT), and amino acid [glutamate, aspartate, glycine, gamma aminobutyric acid
      (GABA), and taurine] level variations in retina from NER, at two different
      nycthemeral periods (11 a.m. and 11 p.m.) and at different ages (2, 6, and 12
      months). In NER, retinal dopaminergic function was decreased as soon as 2 months,
      whereas GABA levels were increased, even if no differences among the different
      ages could be distinguished. These variations were associated to a slight
      increase in 5-HT. Other amino acids tested were not affected by epilepsy, whereas
      taurine decreased with aging in NER as well as in control rats. Retinal 5-HT
      occurs principally as a precursor of melatonin (MEL). A triangular interaction
      may be hypothesized: MEL could decrease DA synthesis or release by enhancing GABA
      activity. Taken together, these results suggest that the retinal physiology is
      affected by the epileptic status and that information transmitted from retina to
      the brain should be affected by epilepsy in NER.

PMID- 16403473
TI  - Regional neuropathology following kainic acid intoxication in adult and aged
      C57BL/6J mice.
AB  - We evaluated regional neuropathological changes in adult and aged male mice
      treated systemically with kainic acid (KA) in a strain reported to be resistant
      to excitotoxic neuronal damage, C57BL/6. KA was administered in a single
      intraperitoneal injection. Adult animals were dosed with 35 mg/kg KA, while aged
      animals received a dose of 20 mg/kg in order to prevent excessive mortality. At
      time-points ranging from 12 h to 7 days post-treatment, animals were sacrificed
      and prepared for histological evaluation utilizing the cupric-silver
      neurodegeneration stain, immunohistochemistry for GFAP and IgG, and lectin
      staining. In animals of both ages, KA produced argyrophilia in neurons throughout
      cortex, hippocampus, thalamus, and amygdala. Semi-quantitative analysis of
      neuropathology revealed a similar magnitude of damage in animals of both ages,
      even though aged animals received less toxicant. Additional animals were
      evaluated for KA-induced reactive gliosis, assayed by an ELISA for GFAP, which
      revealed a 2-fold elevation in protein levels in adult mice, and a 2.5-fold
      elevation in aged animals. Histochemical evaluation of GFAP and lectin staining
      revealed activation of astrocytes and microglia in regions with corresponding
      argyrophilia. IgG immunostaining revealed a KA-induced breach of the blood-brain
      barrier in animals of both ages. Our data indicate widespread neurotoxicity
      following kainic acid treatment in C57BL/6J mice, and reveal increased
      sensitivity to this excitotoxicant in aged animals.

PMID- 16403474
TI  - Immunohistochemical localisation of the voltage gated potassium ion channel
      subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord.
AB  - Voltage gated K+ channels (Kv) are a diverse group of channels important in
      determining neuronal excitability. The Kv superfamily is divided into 12
      subfamilies (Kv1-12) and members of the Kv3 subfamily are highly abundant in the
      CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique expression pattern.
      Since the localisation of Kv subunits is important in defining the roles they
      play in neuronal function, we have used immunohistochemistry to determine the
      distribution of the Kv3.3 subunit in the medulla oblongata and spinal cord of
      rats. Kv3.3 subunit immunoreactivity (Kv3.3-IR) was widespread but present only
      in specific cell populations where it could be detected in somata, dendrites and
      synaptic terminals. Labelled neurones were observed in the spinal cord in laminae
      IV and V, in the region of the central canal and in the ventral horn. In the
      medulla oblongata, labelled cell bodies were numerous in the spinal trigeminal,
      cuneate and gracilis nuclei whilst rarer in the lateral reticular nucleus,
      hypoglossal nucleus and raphe nucleus. Regions containing autonomic efferent
      neurones were predominantly devoid of labelling with only occasional labelled
      neurones being observed. Dual immunohistochemistry revealed that some Kv3.3-IR
      neurones in the ventral medullary reticular nucleus, spinal trigeminal nucleus,
      dorsal horn, ventral horn and central canal region were also immunoreactive for
      the Kv3.1b subunit. The presence of Kv3.3 subunits in terminals was confirmed by
      co-localisation of Kv3.3-IR with the synaptic vesicle protein SV2, the vesicular
      glutamate transporter VGluT2 and the glycine transporter GlyT2. Co-localisation
      of Kv3.3-IR was not observed with VGluT1, tyrosine hydroxylase, serotonin or
      choline acetyl transferase. Electron microscopy confirmed the presence of Kv3.3
      IR in terminals and somatic membranes in ventral horn neurones, but not
      motoneurones. This study provides evidence supporting a role for Kv3.3 subunits
      in regulating neuronal excitability and in the modulation of excitatory and
      inhibitory synaptic transmission in the medulla oblongata and spinal cord.

PMID- 16403475
TI  - Repetitive picture processing: autonomic and cortical correlates.
AB  - Emotionally arousing pictures elicit larger late positive potentials (LPPs) than
      neutral pictures during passive viewing. Moreover, these cortical responses do
      not rely on voluntary evaluation of the hedonic content and are relatively
      unaffected by task demands. In this study, we examined modulation of the late
      positive potential as it varies with stimulus repetition. Three pictures
      (pleasant, neutral, unpleasant) were presented up to 60 times each. Although the
      amplitude of the late positive potential during picture viewing declined with
      stimulus repetition, affective modulation remained intact. On the other hand,
      autonomic responses (skin conductance and heart rate change) habituated rapidly
      with stimulus repetition. These findings suggest that while stimulus detection
      and categorization, reflected in the LPP, is mandatory, autonomic modulation
      reflects initial orienting responses that habituate rapidly.

PMID- 16403476
TI  - The impact of social status on the erythrocyte beta-adrenergic response in
      rainbow trout, Oncorhynchus mykiss.
AB  - The objective of the present investigation was to determine whether chronic
      increases in circulating cortisol concentrations, resulting from the occupation
      of subordinate status in rainbow trout social hierarchies, resulted in an
      enhancement of the erythrocyte adrenergic response. Rainbow trout (Oncorhynchus
      mykiss) were confined in fork length matched pairs for 6 h, 18 h, 48 h or 5-7
      days, and social status was assigned through observations of behaviour.
      Erythrocyte adrenergic responsiveness, determined in vitro as changes in water
      content following incubation with the beta-adrenoreceptor agonist isoproterenol,
      was significantly greater in subordinate than dominant fish at 48 h of social
      interactions but not after 5-7 days, nor when assessed as changes in
      extracellular pH (pHe). However, the activity of the Na+/H+ exchanger (beta-NHE),
      assessed in vitro as the pHe change following incubation with the permeable
      cyclic AMP analogue 8-bromo-cyclic AMP, was significantly lower in subordinate
      fish. The number of erythrocyte membrane-bound adrenergic receptors (Bmax) was
      significantly higher in subordinate than dominant fish at 48 h, but had decreased
      by 5-7 days to a value that was not significantly different from that for
      dominant fish. The apparent dissociation constant (KD) of these receptors was not
      significantly impacted by either social status or interaction time. Finally, the
      relative expressions of beta-3b adrenergic receptor (AR) and beta-NHE mRNA were
      determined using real-time PCR and were found to be minimally affected by social
      rank. Relative to a control group, beta-3b AR mRNA was significantly up-regulated
      in both dominant and subordinate trout at all time periods, whereas the
      expression of beta-NHE was in general significantly down-regulated. Unlike the
      situation in rainbow trout treated with exogenous cortisol, elevations in
      circulating cortisol resulting from low social status did not "pre-adapt" the
      erythrocyte adrenergic response, but rather may have served to offset the
      potentially adverse effects elicited by plasma catecholamines, which were
      elevated during social hierarchy formation.

PMID- 16403478
TI  - Amino acid sequences and phosphorylation sites of emu and rhea eggshell C-type
      lectin-like proteins.
AB  - Avian calcified eggshell layers contain in their organic matrix one or two C-type
      lectin-like proteins. Previously characterized eggshell proteins of this family
      are chicken ovocleidin-17 (OC-17), goose ansocalcin and ostrich struthiocalcins 1
      and 2 (SCA-1, SCA-2). In this report we present the amino acid sequences of two
      emu (Dromaius novaehollandiae) (dromaiocalcin-1 and -2; DCA-1, DCA-2) and of two
      rhea (Rhea americana) (rheacalcin-1 and -2; RCA-1, RCA-2) C-type lectin-like
      eggshell proteins, thus doubling the data set for comparison of these major
      specific eggshell proteins. The ratite proteins can be divided into two groups.
      Group 1, comprising SCA-1, DCA-1 and RCA-1, shows by 70--77% identity of
      sequences, the lack of phosphorylation, and a variable number (7--9) of
      cysteines. Group 2, consisting of SCA-2, DCA-2 and RCA-2, shows 78--85% identical
      sequences, 2--3 phosphorylated serines located at almost identical sites, and
      contains only the common set of six conserved cysteins characteristic for this
      family of proteins. While goose ansocalcin fits perfectly into group 1 with a
      sequence identity of 63--70% to the other members, no phosphorylation, and seven
      cysteines, chicken OC-17 was assigned to group 2 in spite of only 42--47%
      sequence identity (and 37--39% to group 1) because of its two phosphorylated
      serines and its regular set of six cysteines. At present it remains unknown why
      ratites, but not goose or chicken, require two different types of C-type lectin
      like proteins to construct their eggshells.

PMID- 16403479
TI  - Estrogen improves cardiac recovery after ischemia/reperfusion by decreasing tumor
      necrosis factor-alpha.
AB  - BACKGROUND: Estrogen has cardioprotective effects on ischemia/reperfusion (I/R).
      Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine with depressor
      effects on myocardial function and has been suggested to mediate I/R injury.
      Whether cardiac TNFalpha levels are influenced by estrogen status is unknown. We
      investigated the effect of estrogen on TNFalpha levels and TNFalpha receptors in
      the ischemic heart and its role in estrogen modulation of I/R injury. METHODS:
      Hearts were isolated from ovariectomized Sprague-Dawley female rats that were
      treated with either estrogen or placebo for 4 weeks. Working heart preparations
      were subjected to global, no-flow ischemia (25 min) followed by reperfusion (40
      min). RESULTS: I/R increased TNFalpha levels in coronary effluent and in the left
      ventricle (LV) of estrogen-deficient rats, which were decreased by estrogen
      replacement. Moreover, estrogen improved functional recovery (55.0+/-5.0% vs.
      22.0+/-7.0%, P<0.05), decreased LV apoptosis, and reduced myocardial necrosis. To
      further evaluate the role of TNFalpha in I/R injury, a selective TNFalpha
      inhibitor (etanercept) was used in vitro before the ischemic insult. TNFalpha
      inhibition improved functional recovery (39+/-4.4% vs. 22.0+/-7.0%, P<0.05) and
      reduced apoptosis and myocardial necrosis in estrogen-deficient animals but did
      not have a summative protective effect in the hearts of estrogen-replaced
      animals. CONCLUSIONS: These data indicate that estrogen modulates cardiac
      expression of TNFalpha and TNFalpha receptors. Moreover, the cardioprotective
      effects of estrogen are in part mediated by regulation of TNFalpha levels in the
      ischemic heart.

PMID- 16403480
TI  - Ultrasonic destruction of phenol and substituted phenols: a review of current
      research.
AB  - Phenol and some of its derivatives such as chlorophenol and nitrophenol have
      received considerable attention from environmental scientists and engineers, due
      to their undesirable effects in the water environment, where they end up as a
      result of improper disposal methods. As a consequence, research has been
      conducted all around the world with the common goal of reducing their
      concentrations to allowable limits or converting them to non-toxic, non-hazardous
      forms that may easily be handled by natural decay processes. Some of this
      research has focused on ultrasonic techniques, which currently appears to present
      a convenient but as yet unproven method for large scale water remediation. The
      goal of this study is to identify and review some of these studies that are
      directly related with the use of ultrasound in decontaminating effluents with
      phenol residuals and to summarize the main points of interest and problems
      encountered.

PMID- 16403481
TI  - Are sonochemically prepared alpha-amylase protein microspheres biologically
      active?
AB  - Using high-intensity ultrasound, we have synthesized alpha-amylase microspheres.
      The paper presented characterization as well as catalytic experiments of the
      sonochemically-produced microspheres. It also provided an estimate of the
      efficiency of the sonochemical process in converting the native protein to
      microspheres. These microspheres showed a very good enzymatic activity compared
      with the native alpha-amylase. The enzymatic activity of the amylase microspheres
      was 27% of that of the native protein after a short reaction time (3 min), while
      over a longer reaction time (1 h) it reached 56% of the activity of the native
      protein.

PMID- 16403482
TI  - Clinical significance of MUC1 and c-Met RT-PCR detection of circulating tumor
      cells in patients with gastric carcinoma.
AB  - BACKGROUND: Recently, several reverse transcription-polymerase chain reaction (RT
      PCR) techniques have been proven to be useful in the detection of circulating
      tumor cells (CTCs) in cancer patients. We attempted to detect CTCs in patients
      with gastric cancer (GC) using a RT-PCR assay for c-Met and MUC1 and to evaluate
      their clinical value. METHODS: Using a RT-PCR assay, c-Met and MUC1 mRNAs were
      amplified in 52 GC patients and 36 healthy individuals. Analyses were carried out
      for their correlation with the patients' clinicopathologic features, the
      occurrence of new post-operative metastasis, as well as the overall survival
      rates. RESULTS: In the RT-PCR analysis of peripheral blood, 61.5% (32/52) and
      71.2% (37/52) of GC patients were positive for c-Met and MUC1 mRNA, respectively.
      The sensitivity and specificity of either mRNA detected in peripheral blood is
      82.7% and 86.1%, respectively, with an accuracy of 84.1%. The detection of c-Met
      or MUC1 mRNA was significantly correlated with the depth of tumor invasion, lymph
      node metastases, TNM stage, vessel invasion, perineural involvement, and post
      operative metastasis (all P<0.05). Kaplan-Meier analysis demonstrated that the
      overall survival rate of patients with positive c-Met or MUC1 mRNA expression in
      the peripheral blood was significantly shorter than in patients negative for c
      Met or MUC1 mRNA expression (both P<0.05). CONCLUSIONS: Our findings suggest that
      using RT-PCR for the detection of c-Met or MUC1 mRNA may be a promising tool for
      the early detection of micro-metastatic CTCs in GC patients. Combination of these
      2 tumor-specific mRNA markers would increase the detection rate and may be
      clinically helpful in predicting the outcome in GC patients.

PMID- 16403483
TI  - Spread of the radial SNAP: a pitfall in the diagnosis of carpal tunnel syndrome
      using standard orthodromic sensory conduction study.
AB  - OBJECTIVE: To investigate the occurrence of the spread of the radial sensory
      nerve action potential (SNAP) among patients with carpal tunnel syndrome (CTS)
      during standard median orthodromic sensory conduction study (SCS) using index
      finger stimulation. METHODS: We prospectively examined 74 hands in 56 CTS
      patients. We stimulated the index finger using ring electrodes. SNAPs were
      recorded at wrist over median and radial nerves. RESULTS: A spread of radial SNAP
      was clearly identified over the median nerve despite its small amplitude, in
      72/74 hands during stimulation of the base of the index finger. In hands with
      delayed median SNAP, two peaks were observed; however in hands with absence of
      genuine median SNAP, only one peak of the spread was noticed. The proximal
      interphalangeal joint (PIP) stimulation still elicited an identifiable spread in
      47/74 hands. CONCLUSION: This spread phenomenon is a previously undescribed
      pitfall during the standard median orthodromic SCS, frequently occurring in CTS
      patients. SIGNIFICANCE: In severe CTS cases, one may make wrong conclusion of
      normal median sensory latency if unaware of this pitfall.

PMID- 16403484
TI  - Electrocortical and behavioral responses elicited by acute electrical stimulation
      of inferior thalamic peduncle and nucleus reticularis thalami in a patient with
      major depression disorder.
AB  - OBJECTIVE: Our aim was to study electrocortical and behavioral responses elicited
      by 6, 60 and 3/s stimulation of the inferior thalamic peduncle (ITP) and nucleus
      reticularis thalami (Re) in a patient with of major depression disorder resistant
      to psychotherapy, pharmacotherapy and electroconvulsive therapy and candidate to
      be treated by electrical stimulation of the ITP. METHODS: In this patient, two
      multicontact electrodes were implanted bilaterally through frontal coronal
      parasagittal burr-holes with oblique trajectories aiming ITP and Re. Stimulation
      was performed through externalized systems. Referential scalp
      electroencephalographic (EEG) recordings were performed and subjective sensations
      and clinical symptoms reported by patient and changes in responsiveness in single
      response tasks during stimulation trials were systematically recorded. RESULTS:
      Unilateral, low (6/s) and high (60/s) frequency stimulation of either ITP or Re
      produced identical recruiting-like responses or desynchronization-DC shift
      changes predominant at frontopolar region, bilaterally. Billateral, high
      intensity 3/s stimulation or either ITP or Re produced electrocortical responses
      that consisted in generalized 3/s spike-wave complexes predominant at
      frontopolar, frontocentral and frontotemporal regions. However, while ITP
      responses were accompanied by all symptoms described for a spontaneous absence
      attack, Re responses were behaviorly accompanied only by delayed reaction time.
      CONCLUSION: These data suggests that in humans as in cats, ITP and Re are both
      part of a non-specific thalamo-orbitofrontal system normally engaged in cortical
      synchronization, selective attention and sleep. SIGNIFICANCE: Under abnormal
      conditions, ITP and RE may play a role in the physiopathology of typical absence
      attacks and depression disorders.

PMID- 16403485
TI  - Cervical nerve root stimulation. Part I: technical aspects and normal data.
AB  - OBJECTIVE: Cervical nerve root stimulation (CRS) is a technique of assessing the
      proximal segments of motor axons destined to upper extremity muscles. Few studies
      report normal values. The objective was to determine CMAP onset-latencies and
      CMAP amplitude, area, and duration changes in healthy controls for the abductor
      pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles.
      In addition, to determine the tolerability of CRS, as measured by the visual
      analog scale (VAS). METHODS: We studied 21 healthy volunteers prospectively with
      CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally.
      Collision studies were used in all APB recordings. VAS was obtained in all
      subjects. RESULTS: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/
      1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency
      significantly correlated with height for all nerves. The mean change in CMAP
      amplitude and area (%) between most distal stimulation and CRS was: APB reduction
      of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/-
      8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps
      increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change
      between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM,
      increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase
      of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed
      the study. CONCLUSIONS: The present study establishes normative data and
      indicates that CRS is a well-tolerated technique. SIGNIFICANCE: The normal values
      may be used as reference data for the needle CRS technique in the assessment of
      proximal conduction abnormalities.

PMID- 16403486
TI  - A rapid and reliable procedure to localize subdural electrodes in presurgical
      evaluation of patients with drug-resistant focal epilepsy.
AB  - OBJECTIVES: To evaluate a novel method for localization of subdural electrodes in
      presurgical assessment of patients with drug-resistant focal epilepsy. METHODS:
      We studied eight consecutive patients with posterior epilepsy in whom subdural
      electrodes were implanted for presurgical evaluation. Electrodes were detected on
      post-implantation brain CT scans through a semiautomated procedure based on a
      MATLAB routine. Then, post-implantation CT scans were fused with pre-implantation
      MRI to localize the electrodes in relation to the underlying cortical structures.
      The reliability of this procedure was tested by comparing 3D-rendered MR images
      of the electrodes with electrode position as determined by intraoperative digital
      photography. RESULTS: In each patient, all electrodes could be correctly
      localized and visualized in a stereotactic space, thus allowing optimal surgery
      planning. The agreement between the procedure-generated images and the digital
      photographs was good according to two independent raters. The mean mismatch
      between the 3D images and the photographs was 2 mm. CONCLUSIONS: While our
      findings need confirmation on larger samples including patients with anterior
      epilepsy, this procedure allowed to localize subdural electrodes and to establish
      the spatial relationship of each electrode to the underlying brain structure,
      either normal or damaged, on brain convessity, basal and medial cortex.
      SIGNIFICANCE: Being simple, rapid, unexpensive, and reliable, this procedure
      holds promise to be useful to optimize epilepsy surgery planning.

PMID- 16403487
TI  - Ascorbic acid interference in the measurement of serum biochemical parameters: in
      vivo and in vitro studies.
AB  - OBJECTIVES: To investigate the negative interference of ascorbic acid in serum
      biochemical tests in relation to the dose of vitamin C intake and to the time of
      blood collection. DESIGN AND METHODS: Healthy volunteers (n = 18) consumed daily
      doses of vitamin C (0.25-4.0 g) for 1 week and serum parameters were assayed
      prior to the experiment and on the eighth day of consumption. Blood samples were
      collected 4, 12 and 24 h after vitamin C intake. RESULTS: Serum levels of
      ascorbic acid increased significantly after vitamin C ingestion inhibiting urate
      and total bilirubin tests 4 and 12 h after intake (P < 0.01). A significant
      negative interference occurred up to 24 h after consumption of 4 g vitamin C for
      the urate test. In contrast, ingestion of vitamin C did not show interference in
      glucose, triglyceride and cholesterol tests. Addition of ascorbic acid to serum
      inhibited the urate test to a similar extent to that observed after vitamin C
      intake. However, after ingesting vitamin C, the interference for the bilirubin
      test was greater than that of the in vitro interference. CONCLUSIONS: Commonly
      taken doses of supplementary vitamin C interfered negatively with the serum urate
      test based on the Trinder method, and with bilirubin metabolism.

PMID- 16403488
TI  - HPV information needs.
AB  - This chapter discusses the importance of providing women with information about
      human papillomavirus and its role as the causative agent in the development of
      cervical cancer. Studies assessing current levels of knowledge among the general
      public are reviewed. What women need to know will be covered, followed by
      possible strategies for implementation. There are no randomised controlled trials
      to review regarding information for women about human papillomavirus but a number
      of well-conducted qualitative studies explore the issues that are faced both by
      the women undergoing cervical screening and their healthcare providers.

PMID- 16403489
TI  - Cryopreservation of rat hippocampal slices by vitrification.
AB  - Although much interest has attended the cryopreservation of immature neurons for
      subsequent therapeutic intracerebral transplantation, there are no reports on the
      cryopreservation of organized adult cerebral tissue slices of potential interest
      for pharmaceutical drug development. We report here the first experiments on
      cryopreservation of mature rat transverse hippocampal slices. Freezing at 1.2
      degrees C/min to -20 degrees C or below using 10 or 30% v/v glycerol or 20% v/v
      dimethyl sulfoxide yielded extremely poor results. Hippocampal slices were also
      rapidly inactivated by simple exposure to a temperature of 0 degree C in
      artificial cerebrospinal fluid (aCSF). This effect was mitigated somewhat by 0.8
      mM vitamin C, the use of a more "intracellular" version of aCSF having reduced
      sodium and calcium levels and higher potassium levels, and the presence of a 25%
      w/v mixture of dimethyl sulfoxide, formamide, and ethylene glycol ("V(EG)
      solutes"; Cryobiology 48, pp. 22-35, 2004). It was not mitigated by glycerol,
      aspirin, indomethacin, or mannitol addition to aCSF. When RPS-2 (Cryobiology 21,
      pp. 260-273, 1984) was used as a carrier solution for up to 50% w/v V(EG)
      solutes, 0 degree C was more protective than 10 degrees C. Raising V(EG)
      concentration to 53% w/v allowed slice vitrification without injury from
      vitrification and rewarming per se, but was much more damaging than exposure to
      50% w/v V(EG). This problem was overcome by using the analogous 61% w/v VM3
      vitrification solution (Cryobiology 48, pp. 157-178, 2004) containing
      polyvinylpyrrolidone and two extracellular "ice blockers." With VM3, it was
      possible to attain a tissue K(+)/Na(+) ratio after vitrification ranging from 91
      to 108% of that obtained with untreated control slices. Microscopic examination
      showed severe damage in frozen-thawed slices, but generally good to excellent
      ultrastructural and histological preservation after vitrification. Our results
      provide the first demonstration that both the viability and the structure of
      mature organized, complex neural networks can be well preserved by vitrification.
      These results may assist neuropsychiatric drug evaluation and development and the
      transplantation of integrated brain regions to correct brain disease or injury.

PMID- 16403490
TI  - A simple freezing protocol for the use of an open freezing system for
      cryopreservation of ovarian tissue.

PMID- 16403491
TI  - The systemic inflammatory response to exercise in adults with cystic fibrosis.
AB  - Exercise is associated with release of inflammatory mediators in the circulation
      and there is evidence that the exercising muscles and tendons are sources of
      interleukin-6. Due to the catabolic effects of some cytokines, increased release
      in circulation might contribute to alterations in body composition in adults with
      cystic fibrosis. We hypothesised that exercise of moderate intensity would
      generate increased blood concentrations of some inflammatory mediators. We
      investigated the change in blood concentrations of interleukin-6, tumour necrosis
      factor alpha and their soluble receptors after a structured exercise (box
      stepping) of intensity similar to that encountered during activities of daily
      living in 12 adults with cystic fibrosis and mean (95% confidence interval) FEV1
      55.6 (44.4, 66.8)% predicted, body mass index 23.0 (21.3, 24.6) kg/m2 and 12
      healthy subjects. The increments post-exercise for all inflammatory mediators and
      lactate corrected for the work performed until voluntary exhaustion were greater
      for patients, while the total work was less for patients (all p<0.01). Daytime
      variability of the inflammatory mediators was assessed in eight patients and was
      less than the change due to exercise. We report greater increments in circulating
      concentrations of some cytokines with moderate exercise in adults with cystic
      fibrosis compared to healthy subjects.

PMID- 16403492
TI  - Mycobacterium chelonae in a CF patient with anaplastic large cell lymphoma.
AB  - A 13-year-old patient with cystic fibrosis was diagnosed with anaplastic large
      cell lymphoma. At the same time colonization with Mycobacterium chelonae was
      detected in sputum cultures. Despite massive immunosuppression, the patient did
      not show evidence of mycobacterial invasive disease. Colonisation persisted for
      18 months after discontinuation of chemotherapy and was not detected in the 6
      years thereafter. This case highlights the dilemma of differentiating between
      colonisation and infection if mycobacteria are found in CF sputum samples.

PMID- 16403493
TI  - Transcriptional activation by extradenticle in the Drosophila visceral mesoderm.
AB  - decapentaplegic (dpp) is a direct target of Ultrabithorax (Ubx) in parasegment 7
      (PS7) of the embryonic visceral mesoderm. We demonstrate that extradenticle (exd)
      and homothorax (hth) are also required for dpp expression in this location, as
      well as in PS3, at the site of the developing gastric caecae. A 420 bp element
      from dpp contains EXD binding sites necessary for expressing a reporter gene in
      both these locations. Using a specificity swap, we demonstrate that EXD directly
      activates this element in vivo. Activation does not require Ubx, demonstrating
      that EXD can activate transcription independently of homeotic proteins.
      Restoration is restricted to the domains of endogenous dpp expression, despite
      ubiquitous expression of altered specificity EXD. We demonstrate that nuclear EXD
      is more extensively phosphorylated than the cytoplasmic form, suggesting that EXD
      is a target of signal transduction by protein kinases.

PMID- 16403494
TI  - The activity of barley alpha-amylase on starch granules is enhanced by fusion of
      a starch binding domain from Aspergillus niger glucoamylase.
AB  - High affinity for starch granules of certain amylolytic enzymes is mediated by a
      separate starch binding domain (SBD). In Aspergillus niger glucoamylase (GA-I), a
      70 amino acid O-glycosylated peptide linker connects SBD with the catalytic
      domain. A gene was constructed to encode barley alpha-amylase 1 (AMY1) fused C
      terminally to this SBD via a 37 residue GA-I linker segment. AMY1-SBD was
      expressed in A. niger, secreted using the AMY1 signal sequence at 25 mg x L(-1)
      and purified in 50% yield. AMY1-SBD contained 23% carbohydrate and consisted of
      correctly N-terminally processed multiple forms of isoelectric points in the
      range 4.1-5.2. Activity and apparent affinity of AMY1-SBD (50 nM) for barley
      starch granules of 0.034 U x nmol(-1) and K(d) = 0.13 mg x mL(-1), respectively,
      were both improved with respect to the values 0.015 U x nmol(-1) and 0.67 mg x
      mL(-1) for rAMY1 (recombinant AMY1 produced in A. niger). AMY1-SBD showed a 2
      fold increased activity for soluble starch at low (0.5%) but not at high (1%)
      concentration. AMY1-SBD hydrolysed amylose DP440 with an increased degree of
      multiple attack of 3 compared to 1.9 for rAMY1. Remarkably, at low concentration
      (2 nM), AMY1-SBD hydrolysed barley starch granules 15-fold faster than rAMY1,
      while higher amounts of AMY-SBD caused molecular overcrowding of the starch
      granule surface.

PMID- 16403495
TI  - Do current management strategies and guidelines adequately address fracture risk?
AB  - Deciding which patients are appropriate candidates for our effective osteoporosis
      therapies is a clinical challenge. Current guidelines for treating postmenopausal
      osteoporosis are based primarily on bone mineral density (BMD) measurements.
      There is consensus that postmenopausal women with osteoporosis, as defined by T
      scores of -2.5 and lower, are at high risk of fracture and are candidates for
      therapy. However, many older adults without osteoporosis are at increased risk
      for fracture, and most fractures occur in women with higher T-scores. Current BMD
      based guidelines are inconsistent regarding recommendations for treating women
      without osteoporosis. Fracture risk assessment is improved by combining BMD and
      other important risk factors for fracture, especially greater age and history of
      prior fracture. Strategies to estimate absolute fracture risk in individual
      patients are being developed. Revised treatment guidelines, based upon thresholds
      of absolute fracture risk, will provide the opportunity to identify and to treat
      those women who will most benefit from our therapies.

PMID- 16403496
TI  - Skeletal site-specific characterization of orofacial and iliac crest human bone
      marrow stromal cells in same individuals.
AB  - Autologous grafts from axial and appendicular bones commonly used to repair
      orofacial bone defects often result in unfavorable outcome. This clinical
      observation, along with the fact that many bone abnormalities are limited to
      craniofacial bones, suggests that there are significant differences in bone
      metabolism in orofacial, axial and appendicular bones. It is plausible that these
      differences are dictated by site-specificity of embryological progenitor cells
      and osteogenic properties of resident multipotent human bone marrow stromal cells
      (hBMSCs). This study investigated skeletal site-specific phenotypic and
      functional differences between orofacial (maxilla and mandible) and axial (iliac
      crest) hBMSCs in vitro and in vivo. Primary cultures of maxilla, mandible and
      iliac crest hBMSCs were established with and without osteogenic inducers. Site
      specific characterization included colony forming efficiency, cell proliferation,
      life span before senescence, relative presence of surface markers, adipogenesis,
      osteogenesis and transplantation in immunocompromised mice to compare bone
      regenerative capacity. Compared with iliac crest cells, orofacial hBMSCs (OF
      MSCs) proliferated more rapidly with delayed senescence, expressed higher levels
      of alkaline phosphatase and demonstrated more calcium accumulation in vitro.
      Cells isolated from the three skeletal sites were variably positive for STRO 1, a
      marker of hBMSCs. OF-MSCs formed more bone in vivo, while iliac crest hBMSCs
      formed more compacted bone that included hematopoietic tissue and were more
      responsive in vitro and in vivo to osteogenic and adipogenic inductions. These
      data demonstrate that hBMSCs from the same individuals differ in vitro and in
      vivo in a skeletal site-specific fashion and identified orofacial marrow stromal
      cells as unique cell populations. Further understanding of site-specific
      properties of hBMSCs and their impact on site-specific bone diseases and
      regeneration are needed.

PMID- 16403497
TI  - 2-phosphonomethyl-pentanedioic acid (glutamate carboxypeptidase II inhibitor)
      increases threshold for electroconvulsions and enhances the antiseizure action of
      valproate against maximal electroshock-induced seizures in mice.
AB  - This study examined the effect of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA),
      a potent and selective inhibitor of glutamate carboxypeptidase II (GCP II), an
      enzyme releasing glutamate and N-acetyl-aspartate from synaptical terminals, on
      the electroconvulsive threshold in mice. Moreover, the influence of 2-PMPA on the
      anticonvulsant activities of four conventional antiepileptic drugs
      (carbamazepine, phenobarbital, phenytoin and valproate) was evaluated in the
      maximal electroshock-induced seizure test in mice. Results indicated that 2-PMPA
      (at a dose range of 50-200 mg/kg, i.p.) raised the electroconvulsive threshold in
      mice dose-dependently. Linear regression analysis of dose-response relationship
      between the doses of 2-PMPA and their corresponding threshold values allowed the
      calculation of threshold increasing dose by 20% (TID20), which was 109.2 mg/kg.
      Moreover, 2-PMPA administered i.p. at a constant dose of 150 mg/kg (the dose
      increasing the threshold for electroconvulsions) enhanced significantly the
      anticonvulsant action of valproate, by reducing its median effective dose (ED50)
      from 281.4 to 230.1 mg/kg (P<0.05). In contrast, 2-PMPA at the lower dose of 100
      mg/kg (i.p.) had no impact on the antiseizure activity of valproate in the
      maximal electroshock-induced seizure test. Likewise, 2-PMPA at 100 and 150 mg/kg
      did not affect the antiseizure action of carbamazepine, phenobarbital and
      phenytoin against maximal electroshock-induced seizures in mice. Additionally,
      none of the combinations investigated between 2-PMPA (150 mg/kg, i.p.) and
      carbamazepine, phenobarbital, phenytoin and valproate (at their ED50 values)
      produced motor coordination impairment in the chimney test. Pharmacokinetic
      evaluation of interaction between 2-PMPA and valproate revealed that 2-PMPA at
      150 mg/kg selectively increased total brain concentrations of valproate,
      remaining simultaneously without any effect on free plasma concentrations of
      valproate, indicating a pharmacokinetic nature of observed interaction in the
      maximal electroshock-induced seizures in mice. Based on our preclinical data, it
      may be concluded that 2-PMPA possesses a seizure modulating property by
      increasing the electroconvulsive threshold. The reduction of glutamate
      neurotransmission in the brain, as a consequence of inhibition of GCP II activity
      by 2-PMPA, was however insufficient to enhance the anticonvulsant activity of
      conventional antiepileptic drugs, except for valproate, whose antiseizure action
      against maximal electroconvulsions was potentiated by 2-PMPA. Unfortunately, the
      favourable interaction between 2-PMPA and valproate was associated with a
      pharmacokinetic increase in total brain valproate concentrations.

PMID- 16403498
TI  - Effect of YM872, a selective and highly water-soluble AMPA receptor antagonist,
      in the rat kindling and rekindling model of epilepsy.
AB  - We examined antiepileptogenic and anticonvulsant effects of [2,3-dioxo-7-(1H
      imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate
      (YM872), a potent and highly water-soluble alpha-amino-3-hydroxy-5-methyl
      isoxazole-4-propionic acid (AMPA) receptor antagonist, in the rat amygdala
      kindling model of epilepsy. Administration of YM872 significantly suppressed
      fully kindled seizures. Daily pretreatment with YM872 markedly retarded
      development of kindling during drug sessions. We also used the rekindling method
      to investigate the antiepileptogenic effect of YM872 in an attempt to
      differentiate between true and false effects in the conventional method of daily
      administration. The results using the rekindling method suggested that the effect
      of YM872 was truly antiepileptogenic, indicating its possible clinical usefulness
      as an antiepileptogenic drug. We also affirmed the importance of AMPA receptors
      in the seizure expression mechanism and development of kindling-induced
      epileptogenesis.

PMID- 16403499
TI  - Can P-glycoprotein influence the bioavailability of iminosugar-based
      glucosylceramide synthase inhibitors?
AB  - Recently developed glucosylceramide synthase inhibitors with enhanced
      hydrophobicity display increased bioavailability in the central nervous system
      (CNS). Have these improvements come at a potential risk given that the improved
      glucosylceramide synthase inhibitors bear the hallmarks of P-glycoprotein
      substrates? This question warrants attention given the potential to induce
      adverse drug interactions or toxicity, if glucosylceramide synthase inhibitors
      are administered with other P-glycoprotein substrates. The aim of this study was
      to determine if glucosylceramide synthase inhibitors are substrates for the
      multidrug transporter P-glycoprotein. Direct measurements of glucosylceramide
      synthase inhibitors binding to P-glycoprotein were examined, as was their ability
      to modulate transport by the protein. The more hydrophobic glucosylceramide
      synthase inhibitors caused a reduction in drug binding to P-glycoprotein.
      However, the compounds did not achieve this by direct interaction with the
      protein, but through a general membrane perturbation. Furthermore, the
      alterations in drug-P-glycoprotein interaction did not manifest as altered
      cellular accumulation of glucosylceramide synthase inhibitors or altered efficacy
      to reduce cellular glycolipid levels. Consequently, P-glycoprotein expression
      will not contribute significantly to the pharmacokinetic profile of the
      iminosugar glucosylceramide synthase inhibitors.

PMID- 16403500
TI  - Intra-operative recordings of local field potentials can help localize the
      subthalamic nucleus in Parkinson's disease surgery.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be a highly
      effective treatment for Parkinson's disease (PD). However, therapeutic efficacy
      is limited by difficulties in consistently and correctly targeting this nucleus.
      Increasing evidence suggests that there is abnormal synchronization of beta
      frequency band activity (approximately 20 Hz) in the STN of PD patients, as
      reflected in the oscillatory nature of the local field potential (LFP). We
      hypothesized that an increase in the power of the LFP beta activity may provide
      intra-operative confirmation of STN targeting in patients undergoing STN
      implantation for the treatment of advanced PD. Accordingly, we recorded LFPs from
      the four contacts of DBS electrodes as the latter were advanced in 2 mm steps
      from a point 4-6 mm above the intended surgical target point in the STN, to a
      point 4 mm below this. Contacts were configured to give three bipolar recordings
      of LFPs. These were analyzed on 16 sides in 9 patients. The power in the 13-35 Hz
      band recorded at the lowest contact pair underwent a steep but focal increase
      during electrode descent. The depth of the peak beta activity showed excellent
      agreement with the level of the intra-operative clinical stun effect (k
      coefficient = 0.792). The depth of peak beta activity also showed 100%
      specificity and 100% sensitivity for placement within STN in comparison to pre-
      and Post-operative stereotactic MRI. Functional physiological localization of STN
      by the on-line spectral analysis of LFPs is quick to perform and may provide
      information directly relevant to the position of the electrode contact actually
      used for DBS.

PMID- 16403501
TI  - Developmental and triiodothyronine-induced expression of genes encoding
      preprotemporins in the skin of Tago's brown frog Rana tagoi.
AB  - Using RT-PCR, two cDNAs encoding preprotemporins were cloned from a total RNA
      preparation of the skin of Tago's brown frog Rana tagoi. Preprotemporin-1TGa cDNA
      directs the synthesis of temporin-1TGa (FLPILGKLLSGIL.NH2) previously isolated
      from R. tagoi skin. Preprotemporin-1TGb cDNA directs the synthesis of a novel 16
      amino-acid-residue peptide (AVDLAKIANKVLSSLF.NH2) that, atypically for members of
      the temporin family, inhibits the growth of Gram-negative bacteria more
      effectively than Gram-positive bacteria. Preprotemporin-1TGa mRNA and
      preprotemporin-1TGb mRNA were not detected in skin prior to the onset of
      metamorphosis (stage 35) but the levels of the transcripts increased markedly
      during metamorphosis reaching a maximum at stage 38. Exposure of adult animals to
      10(-8) M triiodothyronine (T3) for 72 h enhanced expression of the preprotemporin
      1TGb gene (approximately threefold) but did not significantly change the level of
      expression of the preprotemporin-1TGa gene. Exposure of the animals to 10(-8) M
      T3 and 10(-6) M bisphenol A, an endocrine disrupting chemical that potently
      inhibits the action of thyroid hormones (THs), reduced expression of the
      preprotemporin-1TGb gene by 10-fold and the preprotemporin-1TGa gene by
      threefold. We propose that T3-stimulated synthesis of antimicrobial peptides is
      important in protecting the animal against microorganisms, particularly at
      metamorphosis and during skin moulting, but environmental pollutants can inhibit
      peptide synthesis and render the animal susceptible to invasion by pathogens.

PMID- 16403502
TI  - CRF and stress in fish.
AB  - The endocrine stress response is pivotal in vertebrate physiology. The stress
      hormone cortisol-the end product of the endocrine stress axis-(re-)directs energy
      flows for optimal performance under conditions where homeostasis may be or become
      at risk. Key players in the continuous adaptation process are corticotropin
      releasing factor (CRF) from the hypothalamic nucleus preopticus (NPO), pituitary
      adrenocorticotropic hormone (ACTH) and cortisol produced by the interrenal cells
      in the headkidney (adrenal equivalent of fish). CRF is a member of a large family
      of related peptides that signals through CRF-receptor subtypes specific for
      central and peripheral actions of the peptide. CRF is "chaperoned" by a unique
      and phylogenetically very well-conserved binding protein (CRFBP); the functions
      of the CRFBP can only be speculated on so far, but its mRNA and protein abundance
      are important indicators of the central CRF-system activity, and indeed its mRNA
      levels are altered by restraint stress. Moreover, the unique structure and size
      of the CRFBP provide good tools in phylogenetic studies, that date the CRF-system
      to at least one billion years old. Pro-opiomelanocortin is produced and processed
      to ACTH and endorphin in the hypothalamic NPO and pituitary pars distalis ACTH
      cells, to MSH and acetylated endorphins in the pituitary pars intermedia MSH
      cells. ACTH is the prime corticotrope in acute stress conditions. In carp, MSH,
      considered a mild corticotrope in chronic stress responses in other fish, lacks
      corticotropic effects (in line with the absence of the melanocortin-5 receptor in
      headkidney); yet, an unknown corticotropic signal substance in the pars
      intermedia of carp awaits elucidation. Interesting observations were made on the
      CRF control of pituitary cells. CRF stimulates ACTH-cells, but only when these
      cells experience a mild dopaminergic block. Endorphin, produced in the NPO and
      transported via axons to the pituitary gland in vivo, reverses the stimulatory
      CRF action on MSH-cells to a differential inhibition of N-acetyl beta-endorphin
      release in vitro (MSH release is not affected). We speculate that the
      consistently observed elevation of plasma MSH during chronic stress may exert
      central actions related to feeding and leptin regulated processes. A BOLD-fMRI
      study revealed the functional anatomy of the stress response at work in a
      paradigm, where carp were exposed to a sudden water temperature drop. In carp
      (and other fish), the endocrine stress axis is already operational in very early
      life stages, viz., around hatching and comprises hypothalamic, pituitary, and
      interrenal signaling to adjust the physiology of the hatchling to its dynamically
      changing environment. Understanding of stress during early life stages is
      critical as the consequent rises in cortisol may have long lasting effects on
      survival and fish quality.

PMID- 16403503
TI  - Comparison of cellular strain with applied substrate strain in vitro.
AB  - Strain magnitudes within tenocytes undergoing substrate tensile strain are not
      well defined. It was hypothesized that strain magnitudes at the cellular level
      would reflect those of the applied substrate (equibiaxial or uniaxial) strain. A
      vacuum-operated device was used to apply equibiaxial or uniaxial tension to a
      flexible substrate upon which tenocytes were cultured in monolayer. Images of
      tenocytes labeled with Fura-2, to detect free intracellular calcium ions, and
      MitoFluor Green, to detect mitochondria, were taken prior to strain and for 20
      min during application of static strain. A custom-written, texture correlation
      program computed strain magnitudes in the cell based on the change in pixel
      pattern displacements between images of non-strained and strained cells. On
      average, cellular strain was approximately 37+/-8% and 63+/-11% of the applied
      equibiaxial and uniaxial substrate strain, respectively. The largest cell strains
      were detected in cells oriented parallel to the direction of applied uniaxial
      tensile strain. However, strain magnitudes within a cell were heterogeneous. The
      variance in strain magnitude within and among tenocytes is dependent on cell
      orientation, cell stiffness, cytoskeleton organization, subcellular organelles,
      or placement and type of cell-substrate contacts. Results of the present study
      indicate that cultured tenocytes experience a moderate fraction of the applied
      substrate strain.

PMID- 16403504
TI  - Influence of glottic aperture on the tracheal flow.
AB  - The extra-thoracic mouth-throat area has a major influence on the aerosol
      delivery to the proximal or peripheral intra-thoracic airways. To characterize
      the particle deposition in this area, it is important to investigate first the
      flow structures in this crucial--in relation to the aerosol deposition--region.
      The glottis, which is delimited by the vocal cords and therefore has the
      narrowest passage, generates a laryngeal jet and a reverse flow downstream the
      glottis. It is generally assumed that the glottis has different shapes and cross
      sectional areas at different moments during the respiratory cycle and also
      depends on the average inspiratory flow rate. Therefore, the influence of a
      circular glottal aperture, with a cross-sectional area of 90 mm2 and an
      elliptical and triangular shape, both with an area of 45 mm2, on the flow is
      investigated. However, the area of the circular aperture is twice as big as the
      area of the elliptical one, it has almost no influence on the flow structures. On
      the other hand, the triangular glottal aperture shifts the laryngeal jet in the
      direction of the posterior wall, and generates two pairs of counter rotating
      secondary vortices downstream the glottis, where the circular and elliptical only
      aperture generates one pair of vortices. The difference in pressure drop is more
      dominated by the cross-sectional area than by the shape of the glottis. This
      suggests the need for rendering geometry of future upper airway models even more
      realistic as the appropriate three-dimensional (3D) medical imaging techniques
      are becoming available.

PMID- 16403505
TI  - Removal of As(V) by Cu(II)-, Ni(II)-, or Co(II)-doped goethite samples.
AB  - The present study reports removal of As(V) by adsorption onto laboratory-prepared
      pure and Cu(II)-, Ni(II)-, and Co(II)-doped goethite samples. The X-ray
      diffraction patterns showed only goethite as the crystalline phase. Doping of
      ions in the goethite matrix resulted in shift of d-values. Various parameters
      chosen for adsorption were nature of adsorbent, percentage of doped cations in
      goethite matrix, contact time, solution pH, and percentage of adsorbate. It was
      observed that the pH(pzc) of the goethite surface depended on the nature and
      concentration of metal ions. The surface area as well as the loading capacity
      increased with the increase of dopant percentage in goethite matrix. A maximum
      loading capacity of 19.55 mg/g was observed for 2.7% Cu(II)-doped goethite. The
      adsorption kinetics for Ni(II), Co(II) and for undoped goethite attained a quasi
      equilibrium state after 30 min with almost negligible adsorption beyond this
      time. In case of Cu(II)-doped goethite samples, the quasi-equilibrium state for
      As(V) adsorption was observed after 60 min. At each studied pH condition, it was
      observed that the percentage of adsorption of As(V) decreased in the order Cu(II)
      doped goethite > or = Ni(II)-doped goethite > Co(II)-doped goethite > pure
      goethite. The adsorption followed: Langmuir isotherm, indicating monolayer
      formation.

PMID- 16403506
TI  - Maximum withdrawal speed for Langmuir-Blodgett film deposition of arachidic acid.
AB  - The maximum withdrawal speed of Langmuir-Blodgett (LB) film deposition of
      arachidic acid (AA) was investigated. The quality of LB deposited film was
      determined by the transfer ratio (TR), together with measurements of surface
      roughness using atomic force microscopy (AFM). A Langmuir mini-trough was used to
      provide the surface pressure versus molecular area (pi-A) curves and a flow
      visualization technique was applied to estimate the dynamic contact angles and to
      observe the fluid motion. The effects of hydrophobic and hydrophilic substrates,
      pH and the addition of four different ions, i.e., K+, Ba2+, Cd2+, and Al3+, on
      the withdrawal speed were examined. The "transition point" from liquid to solid
      states on the pi-A curve provided a clear indication of the maximum withdrawal
      speed. The lower the transition point, the higher was the maximum withdrawal
      speed. Stable deposition was possible only if the pH of the solution was
      maintained in a narrow range. The observation of dynamic contact angles and fluid
      motion, particularly the movement of air-liquid interface, was consistent with
      previous findings. Owing to the "soap effect" of the divalent ions Ba2+ and Cd2+,
      the maximum speed for successful LB film deposition without significant water
      entrainment could be extended substantially with the addition of divalent ions.

PMID- 16403507
TI  - Polymer density functional theory approach based on scaling second-order direct
      correlation function.
AB  - A second-order direct correlation function (DCF) from solving the polymer-RISM
      integral equation is scaled up or down by an equation of state for bulk polymer,
      the resultant scaling second-order DCF is in better agreement with corresponding
      simulation results than the un-scaling second-order DCF. When the scaling second
      order DCF is imported into a recently proposed LTDFA-based polymer DFT approach,
      an originally associated adjustable but mathematically meaningless parameter now
      becomes mathematically meaningful, i.e., the numerical value lies now between 0
      and 1. When the adjustable parameter-free version of the LTDFA is used instead of
      the LTDFA, i.e., the adjustable parameter is fixed at 0.5, the resultant
      parameter-free version of the scaling LTDFA-based polymer DFT is also in good
      agreement with the corresponding simulation data for density profiles. The
      parameter-free version of the scaling LTDFA-based polymer DFT is employed to
      investigate the density profiles of a freely jointed tangent hard sphere chain
      near a variable sized central hard sphere, again the predictions reproduce
      accurately the simulational results. Importance of the present adjustable
      parameter-free version lies in its combination with a recently proposed universal
      theoretical way, in the resultant formalism, the contact theorem is still met by
      the adjustable parameter associated with the theoretical way.

PMID- 16403508
TI  - Novel amphiphilic macromolecules and their in vitro characterization as
      stabilized micellar drug delivery systems.
AB  - A series of amphiphilic macromolecules, amphiphilic scorpion-like macromolecules
      (AScMs) and amphiphilic star-like macromolecules (ASMs), were evaluated as
      potential drug delivery systems for intravenous administration. AScMs aggregate
      to form polymeric micelles; whereas the ASMs have a covalently bound core
      structure and behave as unimolecular micelles. Four structurally different AScMs
      and two ASMs were selected for further evaluation focusing on micellar stability
      and biocompatibility. AScMs were determined to have extremely low cmc values,
      indicating excellent thermodynamic stability compared to other polymeric micelle
      systems. Particle sizes of the AScM polymeric micelles and ASM unimolecular
      micelles were between 10 and 20 nm, and remained constant for up to 3 weeks
      storages as aqueous solutions at room temperature (approximately 23 degrees C)
      and 37 degrees C. The dissociation kinetics of the AScM polymeric micelles were
      slowed relative to small molecule surfactant micelles, again indicating enhanced
      kinetic stability. With respect to hemolytic activity, AScMs with longer acyl
      chains were hemolytic; whereas the ASMs had minimal hemolytic activity due to the
      covalently bound structure. Both ASM unimolecular micelles and AScM polymeric
      micelles have excellent micellar stability, but the ASMs are more suitable as
      injectable drug delivery systems due to their low hemolytic activity.

PMID- 16403509
TI  - Preparation of platinum nanoparticles using star-block copolymer with a
      carboxylic core.
AB  - Well-defined star polymers containing a functionalized core supply a molecular
      nanocavity and may be used to control formation of inorganic nanoparticles.
      Herein, platinum (Pt) nanoparticles of 2-4 nm were prepared by using
      (poly(acrylic acid)-b-polystyrene)6 (PAA-b-PS)6 amphiphilic star block copolymer
      as a novel single molecular stabilizer. This PAA core functionalized star polymer
      was obtained by hydrolysis of (poly(tert-butyl acrylate)-b-polystyrene)6 (PtBA-b
      PS)6, which was synthesized by sequential atom transfer radical polymerization
      (ATRP) of tert-butyl acrylate and styrene with an initiator bearing six 2
      bromoisobutyloxyl groups. Pt(IV) ions were loaded by ion exchange to the core of
      the star polymer and Pt nanoparticle stabilized by single star polymer was
      produced by a reduction with NaBH4.

PMID- 16403510
TI  - The cognitive bases of learning to read and spell in Greek: evidence from a
      longitudinal study.
AB  - We conducted a longitudinal study examining the role of phonemic awareness,
      phonological processing, and grammatical skills in the development of reading and
      spelling abilities in Greek. A battery of cognitive, linguistic, and literacy
      tasks was administered to 131 primary school children (65 7-year-olds and 66 9
      year-olds) and was repeated in the following year (8- and 10-year-olds,
      respectively). Phoneme awareness, speech rate, and rapid automatized naming (RAN)
      were concurrent predictors of reading rate at Time 1 (T1), and speech rate was a
      longitudinal predictor of reading rate at Time 2 (T2) when reading at T1 was
      controlled. The predictors of spelling differed from those of reading; phoneme
      awareness and speech rate predicted concurrent attainments at T1, and phoneme
      awareness was a robust longitudinal predictor. Despite the differences in the
      degree of transparency between the Greek and English orthographies, phoneme
      awareness predicts variations in learning to read and spell in both languages.

PMID- 16403511
TI  - Combined megaplex TCR isolation and SMART-based real-time quantitation methods
      for quantitating antigen-specific T cell clones in mycobacterial infection.
AB  - Despite recent advances in measuring cellular immune responses, the quantitation
      of antigen-specific T cell clones in infections or diseases remains challenging.
      Here, we employed combined megaplex TCR isolation and SMART-based real-time
      quantitation methods to quantitate numerous antigen-specific T cell clones using
      limited amounts of specimens. The megaplex TCR isolation covered the repertoire
      comprised of recombinants from 24 Vbeta families and 13 Jbeta segments, and
      allowed us to isolate TCR VDJ clonotypic sequences from one or many PPD-specific
      IFNgamma-producing T cells that were purified by flow cytometry sorting. The
      SMART amplification technique was then validated for its capacity to
      proportionally enrich cellular TCR mRNA/cDNA for real-time quantitation of large
      numbers of T cell clones. SMART amplified cDNA was shown to maintain relative
      expression levels of TCR genes when compared to unamplified cDNA. While the SMART
      based real-time quantitative PCR conferred a detection limit of 10(-5) to 10(-6)
      antigen-specific T cells, the clonotypic primers specifically amplified and
      quantitated the target clone TCR but discriminated other clones that differed by
      >or=2 bases in the DJ regions. Furthermore, the combined megaplex TCR isolation
      and SMART-based real-time quantiation methods allowed us to quantitate large
      numbers of PPD-specific IFNgamma-producing T cell clones using as few as 2 x
      10(6) PBMC collected weekly after mycobacterial infection. This assay system may
      be useful for studies of antigen-specific T cell clones in tumors, autoimmune and
      infectious diseases.

PMID- 16403512
TI  - Development of a rapid, immunochromatographic strip test for serum asialo alpha1
      acid glycoprotein in patients with hepatic disease.
AB  - Serum asialoglycoprotein (desialylated glycoproteins) concentrations have been
      reported to be elevated in patients with hepatic disease as compared with that of
      normal subjects. We recently developed a solid-phase sandwich assay for asialo
      alpha1-acid glycoprotein (AsAGP) as a representative of the serum
      asialoglycoproteins and evaluated the utility of this AsAGP as a diagnostic
      marker for liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC). In this
      study, we developed a rapid, one-step immunochromatographic strip capable of
      specifically detecting AsAGP in serum specimens. We have produced a monoclonal
      antibody (mAb) to AGP, and based on ELISA and Western blot analysis, we have
      selected four hybridoma clones which generated mAbs to recognize AsAGP. In the
      immunochromatographic strip test, one mAb was used for conjugation with colloidal
      gold microparticles. Ricinus communis agglutinin (RCA) was immobilized onto a
      nitrocellulose membrane strip to form a result line in the path of
      chromatographic migration. Likewise, a control line was created above the result
      line by the immobilization of anti-mouse IgG. A serum specimen was then applied
      to the sample pad. The AsAGP in the sample specifically bound to the
      microparticles via mAb (As16.89) and co-migrated upward until the AsAGP was
      sandwiched with the immobilized lectin (RCA), revealing a visible result line.
      The colloidal gold microparticles without bound AsAGP continued to migrate,
      forming a visible control line. Thus, an AsAGP-positive specimen (>1.5 microg/mL)
      yielded a result line and a control line, whereas an AsAGP-negative specimen
      (<1.5 microg/mL) produced only a single control line. The entire test procedure
      was completed in less than 5 min. In order to examine the reliability of the
      testing procedures, we carried out the immunochromatographic strip test with 102
      serum samples and compared the results of these tests with those obtained by
      ELISA. The two methods showed excellent correlation, with 83-100% above/below the
      cut-off value (1.5 microg/mL). Therefore, we concluded that the results of the
      immunochromatographic test are in excellent accordance with those of the sandwich
      ELISA.

PMID- 16403513
TI  - Attenuation of acetaldehyde-induced cell injury by overexpression of aldehyde
      dehydrogenase-2 (ALDH2) transgene in human cardiac myocytes: role of MAP kinase
      signaling.
AB  - Acetaldehyde, the major metabolite of ethanol, which is far more toxic and
      reactive than ethanol, may be responsible for alcohol-induced cardiac damage.
      This study was designed to examine the impact of facilitated acetaldehyde
      metabolism using transfection of human aldehyde dehydrogenase-2 (ALDH2) transgene
      on acetaldehyde- and ethanol-induced cell injury. Fetal human cardiac myocytes
      were transfected with ALDH2, the efficacy of which was verified by flow
      cytometry, Western blot and ALDH2 activity assays. Generation of reactive oxygen
      species (ROS) was detected using 5-(6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate (CM-H2DCFDA). Apoptosis was evaluated by
      4',6'-diamidino-2'-phenylindoladihydrochloride (DAPI) fluorescence microscopy,
      quantitative DNA fragmentation ELISA and caspase 3 activity. Acetaldehyde and
      ethanol elicited overt ROS generation and apoptosis in human cardiac myocytes
      following 24-48 h of incubation. Immunostaining revealed activation of the MAP
      kinase cascades ERK1/2, SAPK/JNK and p38 MAP kinase in acetaldehyde-treated
      myocytes. Interestingly, ALDH2 transgene significantly attenuated acetaldehyde
      induced ROS generation, apoptosis and phosphorylation of ERK1/2 and SAPK/JNK.
      Time-dependent response (0-12 h) revealed ROS accumulation and activation of MAP
      kinases prior to acetaldehyde-induced apoptosis. In addition, acetaldehyde
      induced ROS generation and apoptosis were antagonized by non-enzymatic
      antioxidants. Our results suggested that ALDH2 transgene overexpression may
      effectively alleviate acetaldehyde-elicited cell injury through an ERK1/2 and
      SPAK/JNK-dependent mechanism. Our data are consistent with the notion of
      acetaldehyde as a contributor to alcoholic cardiomyopathy and implicate the
      therapeutic potential of ALDH2 enzyme in alcoholic complications.

PMID- 16403514
TI  - Crystal structure of Bordetella pertussis BugD solute receptor unveils the basis
      of ligand binding in a new family of periplasmic binding proteins.
AB  - Periplasmic binding proteins of a new family particularly well represented in
      Bordetella pertussis have been called Bug receptors. One B.pertussis Bug protein
      is part of a tripartite tricarboxylate transporter while the functions of the
      other 77 are unknown. We report the first structure of a Bug receptor, BugD. It
      adopts the characteristic Venus flytrap motif observed in other periplasmic
      binding proteins, with two globular domains bisected by a deep cleft. BugD
      displays a closed conformation resulting from the fortuitous capture of a ligand,
      identified from the electron density as an aspartate. The structure reveals a
      distinctive alpha carboxylate-binding motif, involving two water molecules that
      bridge the carboxylate oxygen atoms to the protein. Both water molecules are
      hydrogen bonded to a common carbonyl group from Ala14, and each forms a hydrogen
      bond with one carboxylate oxygen atom of the ligand. Additional hydrogen bonds
      are found between the ligand alpha carboxylate oxygen atoms and protein backbone
      amide groups and with a threonine hydroxyl group. This specific ligand-binding
      motif is highly conserved in Bug proteins, indicating that they may all be
      receptors of amino acids or other carboxylated solutes, with a similar binding
      mode. The present structure thus unveils the bases of ligand binding in this
      large family of periplasmic binding proteins, several hundred members of which
      have been identified in various bacterial species.

PMID- 16403515
TI  - A structural basis for the role of nucleotide specifying residues in regulating
      the oligomerization of the Rv1625c adenylyl cyclase from M. tuberculosis.
AB  - The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a
      homodimeric enzyme with two catalytic centers at the dimer interface, and shows
      sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation
      of the substrate-specifying residues in the catalytic domain of Rv1625c, either
      independently or together, to those present in guanylyl cyclases not only failed
      to confer guanylyl cyclase activity to the protein, but also severely abrogated
      the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed
      alterations in the behavior of the mutants on ion-exchange chromatography,
      indicating differences in the surface-exposed charge upon mutation of substrate
      specifying residues. The mutant proteins showed alterations in oligomeric status
      as compared to the wild-type enzyme, and differing abilities to heterodimerize
      with the wild-type protein. The crystal structure of a mutant has been solved to
      a resolution of 2.7A. On the basis of the structure, and additional biochemical
      studies, we provide possible reasons for the altered properties of the mutant
      proteins, as well as highlight unique structural features of the Rv1625c adenylyl
      cyclase.

PMID- 16403517
TI  - The N-terminal half of the peroxisomal cycling receptor Pex5p is a natively
      unfolded domain.
AB  - Targeting of most newly synthesised peroxisomal matrix proteins to the organelle
      requires Pex5p, the so-called PTS1 receptor. According to current models of
      peroxisomal biogenesis, Pex5p interacts with these proteins in the cytosol,
      transports them to the peroxisomal membrane and catalyses their translocation
      across the membrane. Presently, our knowledge on the structural details behind
      the interaction of Pex5p with the cargo proteins is reasonably complete. In
      contrast, information regarding the structure of the Pex5p N-terminal half (a
      region containing its peroxisomal targeting domain) is still limited. We have
      recently observed that the Stokes radius of this Pex5p domain is anomalously
      large, suggesting that this portion of the protein is either a structured
      elongated domain or that it adopts a low compactness conformation. Here, we
      address this issue using a combination of biophysical and biochemical approaches.
      Our results indicate that the N-terminal half of Pex5p is best described as a
      natively unfolded pre-molten globule-like domain. The implications of these
      findings on the mechanism of protein import into the peroxisome are discussed.

PMID- 16403516
TI  - The anti-angiogenic peptide anginex disrupts the cell membrane.
AB  - Anginex is a synthetic beta-sheet peptide with anti-angiogenic and anti-tumor
      activity. When added to cultured endothelial cells at concentrations ranging from
      2.5 microM to 25 microM, anginex induced cell death, which was reflected by a
      strong increase of subdiploid cells and fragments, loss of cellular ATP, and LDH
      release. Cytotoxicity remained the same whether cells were treated with anginex
      at 4 degrees C or at 37 degrees C. At low temperatures, fluorescein-conjugated
      anginex accumulated on the endothelial surface, but did not reach into the
      cytoplasm, indicating that the cell membrane is the primary target for the
      peptide. Within minutes of treatment, anginex caused endothelial cells to take up
      propidium iodide and undergo depolarization, both parameters characteristic for
      permeabilization of the cell membrane. This process was amplified when cells were
      activated with hydrogen peroxide. Red blood cell membranes were essentially
      unaffected by anginex. Anginex bound lipid bilayers with high affinity and with a
      clear preference for anionic over zwitterionic phospholipids. Structural studies
      by circular dichroism and solid-state nuclear magnetic resonance showed that
      anginex forms a beta-sheet and adopts a unique and highly ordered conformation
      upon binding to lipid membranes. This is consistent with lipid micellization or
      the formation of pore-forming beta-barrels. The data suggest that the
      cytotoxicity of anginex stems from its ability to target and disrupt the
      endothelial cell membrane, providing a possible explanation for the angiostatic
      activity of the peptide.

PMID- 16403518
TI  - Subcellular positioning of F plasmid mediated by dynamic localization of SopA and
      SopB.
AB  - SopA, SopB proteins and the cis-acting sopC DNA region of F plasmid are essential
      for partitioning of the plasmid, ensuring proper subcellular positioning of the
      plasmid DNA molecules. We have analyzed by immunofluorescence microscopy the
      subcellular localization of SopA and SopB. The majority of SopB molecules formed
      foci, which localized frequently with F plasmid DNA molecules. The foci increased
      in number in proportion to the cell length. Interestingly, beside the foci
      formation, SopB formed a spiral structure that was dependent on SopA, which also
      formed a spiral structure, independent of the presence of SopB, and these two
      structures partially overlapped. On the basis of these results and previous
      biochemical studies together with our simulations, we propose a theoretical model
      named "the reaction-diffusion partitioning model", using reaction-diffusion
      equations that explain the dynamic subcellular localization of SopA and SopB
      proteins and the subcellular positioning of F plasmid. We hypothesized that
      sister copies of plasmid DNA compete with each other for sites at which SopB
      multimer is at the optimum concentration. The plasmid incompatibility mediated by
      the Sop system might be explained clearly by this hypothesis.

PMID- 16403519
TI  - The oxidation state of DJ-1 regulates its chaperone activity toward alpha
      synuclein.
AB  - DJ-1 has been reported to have chaperone activity by preventing the aggregation
      of some proteins, and by structural analogy to Hsp31. The L166P mutation has been
      linked to a familial early onset form of Parkinson's disease (PD). Since the
      aggregation of alpha-synuclein is believed to be a critical step in the etiology
      of PD, we have investigated the interaction of wild-type DJ-1 and its oxidized
      forms with alpha-synuclein. Native (unoxidized) DJ-1 did not inhibit alpha
      synuclein fibrillation, and no evidence for stable interactions between alpha
      synuclein and native DJ-1 was observed. However, DJ-1 is very susceptible to
      oxidation by the addition of two oxygen atoms to form the sulfinic acid of Cys106
      (2O DJ-1) (no 1O oxidized state is detectable). 2O DJ-1 was readily prepared by
      the addition of H(2)O(2) at concentrations up to a 20-fold molar excess. The
      oxidation of Cys106 to the sulfinic acid had minimal effect on the structural
      properties of DJ-1. However, 2O DJ-1 was very effective in preventing the
      fibrillation of alpha-synuclein, and only this form of DJ-1 appears to have
      significant anti-aggregation properties against alpha-synuclein. Further
      oxidation of DJ-1 leads to loss of some secondary structure, and to loss of the
      ability to inhibit alpha-synuclein fibrillation. Our observations confirm the
      suggestion that DJ-1 may act as an oxidative-stress-induced chaperone to prevent
      alpha-synuclein fibrillation. Since oxidative stress has been associated with PD,
      this observation may explain why mutations of DJ-1 could be a contributing factor
      in PD, and also indicates that excess oxidative stress could also lead to
      enhanced alpha-synuclein aggregation and hence PD.

PMID- 16403520
TI  - Islet amyloid polypeptide inserts into phospholipid monolayers as monomer.
AB  - Amyloid deposits in the pancreatic islets of Langerhans are thought to be a main
      factor responsible for death of the insulin-producing islet beta-cells in type 2
      diabetes. It is hypothesized that beta-cell death is related to interaction of
      the 37 amino acid residue human islet amyloid polypeptide (hIAPP), the major
      constituent of islet amyloid, with cellular membranes. However, the mechanism of
      hIAPP-membrane interactions is largely unknown. Here, we study the nature and the
      molecular details of the initial step of hIAPP-membrane interactions by using the
      monolayer technique. It is shown that both freshly dissolved hIAPP and the non
      amyloidogenic mouse IAPP (mIAPP) have a pronounced ability to insert into
      phospholipid monolayers, even at lipid packing conditions that exceed the
      conditions that occur in biological membranes. In contrast, the fibrillar form of
      hIAPP has lost the ability to insert. These results, combined with the
      observations that both the insertion kinetics and the dependence of insertion on
      the initial surface pressure are similar for freshly dissolved hIAPP and mIAPP,
      indicate that hIAPP inserts into phospholipid monolayers most likely as a
      monomer. In addition, our results suggest that the N-terminal part of hIAPP,
      which is nearly identical with that of mIAPP, is largely responsible for
      insertion. This is supported by experiments with hIAPP fragments, which show that
      a peptide consisting of the 19 N-terminal residues of hIAPP efficiently inserts
      into phospholipid monolayers, whereas an amyloidogenic decapeptide, consisting of
      residues 20-29 of hIAPP, inserts much less efficiently. The results obtained here
      suggest that hIAPP monomers might insert with high efficiency in biological
      membranes in vivo. This process could play an important role as a first step in
      hIAPP-induced membrane damage in type 2 diabetes.

PMID- 16403521
TI  - Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4
      3.
AB  - The development of resistance to anti-retroviral drugs targeted against HIV is an
      increasing clinical problem in the treatment of HIV-1-infected individuals. Many
      patients develop drug-resistant strains of the virus after treatment with
      inhibitor cocktails (HAART therapy), which include multiple protease inhibitors.
      Therefore, it is imperative that we understand the mechanisms by which the viral
      proteins, in particular HIV-1 protease, develop resistance. We have determined
      the three-dimensional structure of HIV-1 protease NL4-3 in complex with the
      potent protease inhibitor TL-3 at 2.0 A resolution. We have also obtained the
      crystal structures of three mutant forms of NL4-3 protease containing one (V82A),
      three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point
      mutations in complex with TL-3. The three protease mutants arose sequentially
      under ex vivo selective pressure in the presence of TL-3, and exhibit fourfold,
      11-fold, and 30-fold resistance to TL-3, respectively. This series of protease
      crystal structures offers insights into the biochemical and structural mechanisms
      by which the enzyme can overcome inhibition by TL-3 while recovering some of its
      native catalytic activity.

PMID- 16403522
TI  - R-state haemoglobin with low oxygen affinity: crystal structures of deoxy human
      and carbonmonoxy horse haemoglobin bound to the effector molecule L35.
AB  - Although detailed crystal structures of haemoglobin (Hb) provide a clear
      understanding of the basic allosteric mechanism of the protein, and how this in
      turn controls oxygen affinity, recent experiments with artificial effector
      molecules have shown a far greater control of oxygen binding than with natural
      heterotropic effectors. Contrary to the established text-book view, these non
      physiological compounds are able to reduce oxygen affinity very strongly without
      switching the protein to the T (tense) state. In an earlier paper we showed that
      bezafibrate (BZF) binds to a surface pocket on the alpha subunits of R state Hb,
      strongly reducing the oxygen affinity of this protein conformation. Here we
      report the crystallisation of Hb with L35, a related compound, and show that this
      binds to the central cavity of both R and T state Hb. The mechanism by which L35
      reduces oxygen affinity is discussed, in relation to spectroscopic studies of
      effector binding.

PMID- 16403523
TI  - Substrate transfer from the chaperone Hsp70 to Hsp90.
AB  - Hsp90 is an essential chaperone protein in the cytosol of eukaryotic cells. It
      cooperates with the chaperone Hsp70 in defined complexes mediated by the adaptor
      protein Hop (Sti1 in yeast). These Hsp70/Hsp90 chaperone complexes play a major
      role in the folding and maturation of key regulatory proteins in eukaryotes.
      Understanding how non-native client proteins are transferred from one chaperone
      to the other in these complexes is of central importance. Here, we analyzed the
      molecular mechanism of this reaction using luciferase as a substrate protein. Our
      experiments define a pathway for luciferase folding in the Hsp70/Hsp90 chaperone
      system. They demonstrate that Hsp70 is a potent capture device for unfolded
      protein while Hsp90 is not very efficient in this reaction. When Hsp90 is absent,
      in contrast to the in vivo situation, Hsp70 together with the two effector
      proteins Ydj1 and Sti1 exhibits chaperone activity towards luciferase. In the
      presence of the complete chaperone system, Hsp90 exhibits a specific positive
      effect only in the presence of Ydj1. If this factor is absent, the transferred
      luciferase is trapped on Hsp90 in an inactive conformation. Interestingly,
      identical results were observed for the yeast and the human chaperone systems
      although the regulatory function of human Hop is completely different from that
      of yeast Sti1.

PMID- 16403524
TI  - Amyloid-beta peptide disruption of lipid membranes and the effect of metal ions.
AB  - Beta-amyloid peptide (Abeta), which is cleaved from the larger trans-membrane
      amyloid precursor protein, is found deposited in the brain of patients suffering
      from Alzheimer's disease and is linked with neurotoxicity. We report the results
      of studies of Abeta1-42 and the effect of metal ions (Cu2+ and Zn2+) on model
      membranes using 31P and 2H solid-state NMR, fluorescence and Langmuir Blodgett
      monolayer methods. Both the peptide and metal ions interact with the phospholipid
      headgroups and the effects on the lipid bilayer and the peptide structure were
      different for membrane incorporated or associated peptides. Copper ions alone
      destabilise the lipid bilayer and induced formation of smaller vesicles but when
      Abeta1-42 was associated with the bilayer membrane copper did not have this
      effect. Circular dichroism spectroscopy indicated that Abeta1-42 adopted more
      beta-sheet structure when incorporated in a lipid bilayer in comparison to the
      associated peptide, which was largely unstructured. Incorporated peptides appear
      to disrupt the membrane more severely than associated peptides, which may have
      implications for the role of Abeta in disease states.

PMID- 16403525
TI  - Requirement of new protein synthesis of a transcription factor for memory
      consolidation: paradoxical changes in mRNA and protein levels of C/EBP.
AB  - Some specific transcription factors are essential for memory consolidation across
      species. However, it is still unclear whether only the activation of
      constitutively expressed forms of these conserved transcription factors is
      involved in memory consolidation or their de novo synthesis also occurs after
      learning. This question has remained unanswered partly because of the lack of an
      efficient method for the determination of copy numbers of particular mRNAs in
      single neurons, which allows the detection of new transcription at the cellular
      level. Here we applied a newly developed protocol of single-cell quantitative
      real-time polymerase chain reaction (qRT-PCR) to single neurons playing an
      important role in associative learning. Specifically, we examined the changes in
      the mRNA and protein expression levels of a highly conserved transcription
      factor, CCAAT/enhancer binding protein (C/EBP), in the paired B2 motoneurons of
      the pond snail Lymnaea stagnalis. These buccal neurons are involved in the motor
      control of feeding behavior, with a potentially important role in conditioned
      taste aversion (CTA). Single-cell qRT-PCR revealed a significant decrease in
      LymC/EBP mRNA copy numbers in the B2 motoneurons during memory consolidation
      after CTA training. By contrast, isoelectric focusing and immunoblotting of
      extracts of the buccal ganglia showed that translation and phosphorylation levels
      of LymC/EBP significantly increased during memory consolidation. The C/EBP-like
      immunoreactivity in the B2 motoneurons, which are the major immunopositive
      component in the buccal ganglia, also significantly increased during memory
      consolidation, suggesting that the main source of increase in the level of
      protein in the buccal ganglia are the B2 motoneurons. Thus, early memory
      consolidation after CTA learning in L.stagnalis involves both the rapid synthesis
      and phosphorylation of LymC/EBP as well as the rapid breakdown of LymC/EBP mRNA
      in the neural network controlling feeding, suggesting that all of these processes
      play a role in the function of C/EBP in memory consolidation.

PMID- 16403526
TI  - Molecular dynamics simulations and free energy analyses on the dimer formation of
      an amyloidogenic heptapeptide from human beta2-microglobulin: implication for the
      protofibril structure.
AB  - Amyloid formation is associated with many neurodegenerative diseases. Recent
      findings suggest that early oligomeric aggregates could be major sources of
      toxicity. We present a computational investigation of the first step of amyloid
      initiation-dimer formation of a seven residue peptide (NHVTLSQ) from human beta2
      microglobulin at pH 2.0, which renders +2.0 units charges to each peptide. A
      total of over 1.2 micros of simulations with explicit solvent and 1.0 micros of
      simulations with implicit solvent were conducted. Main-chain conformational
      restraint was applied to facilitate the formation of ordered dimers. An
      antiparallel beta-sheet with six main-chain hydrogen bonds was dominant in the
      implicit solvent simulations. In contrast, no stable dimers were observed in the
      two negative controls, the mouse heptapeptide (KHDSMAE, +3.0 units charges) and
      the scrambled human heptapeptide (QVLHTSN). Explicit solvent simulations
      presented a more complex scenario. The wild-type human heptapeptide formed
      predominantly antiparallel beta-sheets ( approximately 38%) although parallel
      ones ( approximately 12%) were also observed. Hydrophobic contacts preceded
      hydrogen bond saturation in the majority of the association events in the
      explicit solvent simulations, highlighting the important role of hydrophobic
      interaction in amyloid initiation. The fact that the mouse dimer dissociated
      immediately after the removal of conformational restraint suggests that the
      higher conformational entropy barrier, along with the stronger charge repulsion
      and weaker hydrophobic interaction, contributed to its inability to form amyloid
      fibril. The closeness of positive charge pairs in the dimers of the scrambled
      human heptapeptide may prohibit further beta-sheet extension and fibril growth.
      Combining the results from simulations and free energy analyses, we propose that
      the building block for this amyloid fibril is an antiparallel dimer with a two
      residue register shift and six main-chain hydrogen bonds. A double-layer
      protofibril structure is also proposed in which two antiparallel beta-sheets face
      each other and are held together by hydrophobic staples and hydrogen bonds of the
      polar side-chains.

PMID- 16403527
TI  - Polymorphism of bulged-out residues in HIV-1 RNA DIS kissing complex and
      structure comparison with solution studies.
AB  - All retroviruses encapsidate their genome as a dimer of homologous single
      stranded RNAs. The dimerization initiation site (DIS) of human immunodeficiency
      virus type 1 (HIV-1) is located in the 5'-untranslated region of the viral genome
      and consists of a hairpin with a 6 nt self-complementary loop sequence. Genomic
      RNA dimerization, a crucial step for virion infectivity, is promoted by the
      formation of a loop-loop complex (or kissing complex) between two DIS hairpins.
      Crystal structures for the subtypes A, B and F of the HIV-1 DIS kissing complex
      have now been solved at 2.3 A, 1.9 A and 1.6 A, respectively. They revealed a
      polymorphism of bulged-out residues showing clearly that their conformation is
      not a mere consequence of crystal packing. They also provide more insights into
      ion binding, hydration, and RNA conformation and flexibility. In particular, we
      observed the binding of spermine to the loop-loop helix, which displaced a
      magnesium cation important for subtype A DIS dimerization. The excellent
      agreement between X-ray structures and the results of chemical probing and
      interference data on larger viral RNA fragments shows that the crystal structures
      are relevant for the DIS kissing complex present in solution and in viral
      particles. Accordingly, these structures will be helpful for designing new drugs
      derived from aminoglycoside antibiotics and targeted against the RNA dimerization
      step of the viral life-cycle.

PMID- 16403528
TI  - HPA axis functioning associated with transition to psychosis: combined DEX/CRH
      test.
AB  - We investigated functioning of the hypothalamic-pituitary-adrenal (HPA) axis in
      12 young people at ultra high risk for developing psychosis, using the combined
      dexamethasone corticotrophin releasing hormone (DEX/CRH) test. Over a two year
      period, three of the 12 participants developed an acute psychosis. Descriptive
      analysis of the data indicated that contrary to expectations, participants who
      did not make the transition to psychosis had on average higher cortisol levels at
      the latter stages of the test, as well as a greater severity of depression and
      anxiety symptoms, than participants who subsequently developed psychosis. These
      preliminary results suggest that dysregulated HPA-axis functioning in individuals
      at high risk for psychosis may be associated more with comorbid depression
      symptoms than factors specifically related to the process of emerging psychosis
      illness.

PMID- 16403529
TI  - Sensitivity to carbon dioxide in drug-naive subjects with post-traumatic stress
      disorder.
AB  - Post-traumatic stress disorder (PTSD) is currently classified as an anxiety
      disorder in DSM-IV, and as a neurosis or stress-related disorder in ICD-10. It
      shares many features with depression. Sensitivity to carbon dioxide (CO2), a
      classic provocation agent in the proto-typical anxiety disorder, panic disorder,
      has not been tested in PTSD. Twenty rigorously ascertained drug-naive subjects
      with PTSD inhaled a single vital capacity inhalation of 35% CO2; before and after
      the inhalation they completed measures of PTSD and panic anxiety, and were rated
      for the presence of a panic attack. These results were retrospectively compared
      with those of 39 healthy volunteers and 17 patients with panic disorder
      previously studied by the same research group. PTSD symptoms were not exacerbated
      by CO2. Two out of twenty PTSD subjects panicked. PTSD subjects' responses were
      indistinguishable from those of healthy volunteers, and differed from those of
      subjects with panic disorder. The lack of sensitivity to carbon dioxide in PTSD
      subjects in the present study adds to the literature on the differences between
      PTSD and other anxiety disorders, and to that on the specificity of the CO2
      challenge in panic disorder.

PMID- 16403530
TI  - Plasma S-100B protein in Chinese patients with schizophrenia: comparison with
      healthy controls and effect of antipsychotics treatment.
AB  - PURPOSE: To examine the possibility that structural damage to the brain may play
      a role in the pathogenesis of schizophrenia by measuring the level of plasma S
      100B, a calcium-binding protein found predominantly in the cytosol of glial
      cells. METHOD: Fifty-seven Chinese psychiatric inpatients who met DSM-IV
      diagnosis of schizophrenia and 60 healthy controls were enrolled in the study.
      Patients were assessed with the Positive and Negative Symptoms Scale (PANSS) at
      admission and at 12 weeks after treatment. Plasma samples were collected from
      patients and controls and S-100B protein was assayed using ELISA. RESULTS: (1) 29
      of 57 patients (50.9%) showed increased S-100B level compared to the mean level
      of 60 healthy controls (p<0.005) vs. only 1 of 60 (1.67%) controls. The S-100B
      levels of unmedicated (0.119+/-0.059microg/L) and medicated patients (0.117+/
      .0.057microg/L) were significantly higher than controls (0.067+/-0.022microg/L,
      both p<0.001), and S-100B levels of unmedicated patients were higher than those
      of medicated patients (p=0.024); (2) at admission, S-100B level was positively
      correlated with total score of PANSS (r=0.269, p=0.043), especially with negative
      subscore of PANSS (r=0.306, p=0.021), but the correlation was no longer present
      after patients were treated by anti-psychotic agents. CONCLUSION: The S-100B
      levels of patients with schizophrenia are significantly higher than that of
      healthy controls, and the S-100B level is associated with severity of
      psychopathology, particularly negative symptoms, indicating that patients with
      schizophrenia may suffer structural damage to central nervous system. The
      concentration of S-100B may also be associated with treatment progress.

PMID- 16403531
TI  - Isolated abducens nerve palsy as a regional variant of Guillain-Barre syndrome.
AB  - The authors reviewed clinical profiles and laboratory findings for 100 cases of
      abducens nerve paresis without impairment of the other cranial nerves, limb
      weakness, and ataxia throughout the clinical course. Review of the medical
      records of 9300 patients referred to our neuoroimmunological laboratory for serum
      anti-ganglioside antibody testing. Information was obtained from each primary
      physician on symptoms of preceding infection; initial symptoms; neurological
      signs during the illness; the clinical course; treatment provided; and outcome.
      Isolated abducens nerve paresis was present in 100 patients and bilateral paresis
      in 29. Tentative diagnoses made by the primary physicians on request of anti
      ganglioside antibody testing were abducens nerve palsy (n = 68), Fisher syndrome
      (n = 14), acute ophthalmoparesis without ataxia (n = 14). Symptoms of infection
      anteceded in 63. Tendon reflexes were absent or decreased in 27. Distal
      paresthesias were experienced by seven. Serum anti-GQ1b antibody was positive in
      25. These findings suggest that some cases of isolated abducens nerve palsy can
      be categorized as a regional variant of Guillain-Barre syndrome or mild form of
      Fisher syndrome.

PMID- 16403532
TI  - Regulatory T cell adjustment of quorum growth thresholds and the control of local
      immune responses.
AB  - The consequences of regulatory T cell (Treg) inhibition of interleukine 2
      secretion is examined by mathematical modelling. We demonstrate that cytokine
      dependent growth exhibits a quorum T cell population threshold that determines if
      immune responses develop on activation. Secretion inhibition manipulates the
      growth dynamics and effectively increases the quorum threshold, i.e. to develop
      immune responses a higher number of T cells need to be activated. Thus Treg
      induced secretion inhibition can provide a mechanism for tissue specific
      regulation of the balance between suppression (control) and immune responses, a
      balance that can be varied at the local tissue level through the regulation of
      the local active Treg population size. However, nonspecific inhibition is prone
      to escape of initially controlled autoimmune T cells through cross reactivity to
      pathogens and bystander proliferation on unrelated immune responses.

PMID- 16403533
TI  - Simulating the evolution of signal transduction pathways.
AB  - We use a generic model of a network of proteins that can activate or deactivate
      each other to explore the emergence and evolution of signal transduction networks
      and to gain a basic understanding of their general properties. Starting with a
      set of non-interacting proteins, we evolve a signal transduction network by
      random mutation and selection to fulfill a complex biological task. In order to
      validate this approach we base selection on a fitness function that captures the
      essential features of chemotactic behavior as seen in bacteria. We find that a
      system of as few as three proteins can evolve into a network mediating chemotaxis
      like behavior by acting as a "derivative sensor". Furthermore, we find that the
      dynamics and topology of such networks show many similarities to the natural
      chemotaxis pathway, that the response magnitude can increase with increasing
      network size and that network behavior shows robustness towards variations in
      some of the internal parameters. We conclude that simulating the evolution of
      signal transduction networks to mediate a certain behavior may be a promising
      approach for understanding the general properties of the natural pathway for that
      behavior.

PMID- 16403534
TI  - Modelling of auxin transport affected by gravity and differential radial growth.
AB  - When a tree stem deviates from verticality, as a result of different
      environmental factors, patterns of differential radial growth appear. Higher
      rates of wood production have been observed on the lower side of the tree and
      lower rates in the opposite side. Biological studies on plant hormones have shown
      that the concentration of auxin induces radial growth. They also have
      demonstrated the redistribution of auxin transport in response to gravity. Auxin
      is then designated as a mediator for differential growth. This paper presents a
      model for three-dimensional (3-D) auxin transport in conifer trees, which
      includes gravity dependence. We obtain realistic heterogeneous patterns of auxin
      distribution over the tree. Then, we propose a law of growth based on auxin
      concentration to simulate successive differential radial growths. The predicted
      growths are compared with experimental results of reconstruction of 3-D annual
      growth of Radiata pine.

PMID- 16403535
TI  - Systematic discovery of the grammar of translational inhibition by RNA hairpins.
AB  - Recent discovery of gene expression mechanisms has propelled molecular genetics
      to a state of rapid development, a state likely to persist due to continuing
      advances in understanding control systems of fundamental cellular processes. An
      algorithm for that advancement starts in this paper with a gene of interest and a
      characteristic function of that gene. The set of all genes with counteracting
      function is identified by pathway searches. Also associated with the first gene
      is the set of the genes which byproducts of its transcription might downregulate,
      identified relative to searches involving sequence alignments. Our focus is the
      intersection of the counteracting gene set and the downregulated gene set. The
      result is hypothesis generation. Examples of and predictions from this approach
      are given in the context of apoptosis. Also discussed is application of the
      algorithm to rational drug design from a new development platform.

PMID- 16403536
TI  - Carbon, nitrogen, phosphorus and heavy metal budgets: how large is the eelgrass
      (Zostera marina L.) sink in a temperate estuary?

PMID- 16403537
TI  - Distribution of organochlorines in the dissolved and suspended phase of the sea
      surface microlayer and seawater in Hong Kong, China.
AB  - Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were
      measured in the dissolved and suspended particulate phase in the sea-surface
      microlayer (SML) and subsurface water (SSW) collected from Hong Kong's coastal
      environment. The concentration ranges (pg/L) for summation sigmaHCHs, summation
      sigmaDDTs and summation sigmaPCBs in the SSW dissolved phase (DP i.e. sum of
      truly dissolved and colloidal phase) were 409-940 (mean 602), 774-5583 (mean
      1908) and 266-433 (mean 278), respectively. The concentration ranges (pg/L) for
      summation sigmaHCHs, summation sigmaDDTs and summation sigmaPCBs in SSW suspended
      particulate matter (SPM) were <5-85 (mean 59), 358-1369 (mean 787) and 85.6-273
      (mean 172), respectively. The enrichment factor of PCBs and OCPs in the SML
      varied between 1.1 and 4.5 for the DP, and 0.4-8.2 for the SPM. The distribution
      of contaminants between DP and SPM in both the SML and SSW indicates that
      particulate matter plays an important role in the distribution and fate of DDTs
      and PCBs, but not for HCH isomers. The Pearl River Estuary is likely to be a
      major source of contaminants transported to Hong Kong.

PMID- 16403538
TI  - Characterization and source of oil contamination on the beaches and seabird
      corpses, Sable Island, Nova Scotia, 1996-2005.
AB  - During April 1996-May 2005, 2343 oiled seabird corpses were recorded in beach
      surveys conducted on Sable Island, Nova Scotia. One hundred eighty-three samples
      of oil were collected from the beaches and from the feathers of bird corpses. Gas
      chromatographic (GC/FID) analysis was used to identify generic oil type and
      likely marine source. During this period, at least 74 marine oil discharge events
      were probably responsible for beached pelagic tar and contamination of seabird
      corpses found on Sable Island, of which 77.0% were crude oils, 14.9% were fuel
      oils, and 8.1% were bilge oil mixtures. While fuel and bilge oils may be
      discharged by all vessel and platform types, crude oil discharges are associated
      with tanker operations. This study demonstrates that oiling of the sea from
      tankers remains a serious wildlife issue in the Northwest Atlantic.

PMID- 16403539
TI  - The influence of wavelength and probe configuration on findings of a skin
      vasoconstriction test when using laser Doppler perfusion devices.
AB  - The aim of this study was to establish the degree to which a standardized test
      based on laser Doppler blood flow measurement is dependent on the particular
      equipment set-up being used. For this purpose, we examined finger skin blood flow
      with laser Doppler instruments in 20 healthy subjects. In laser Doppler perfusion
      monitoring (LDPM), we used a custom-made probe with two detecting fibers placed
      0.25 and 1.2 mm from the illuminating fiber, respectively, and two laser Doppler
      perfusion imagers (LDPI) with a wavelength of 632.8 nm and 780 nm, respectively.
      Warming of the hand was achieved with a Peltier element, and reflex
      vasoconstriction was induced by immersing the other hand for 3 min into a water
      bath kept at 15 degrees C. As a measure for the change in skin blood flow, a
      vasoconstriction index (VAC: cooling/before cooling) was calculated and used for
      the comparison of the different devices. VAC values gathered around 0.6 for all
      devices. However, LDPI with a wavelength of 632.8 nm showed a slightly higher VAC
      index, and the difference was significant. We conclude that using a standardized
      test is the most appropriate for monitoring changes in blood flow rather than
      recording and comparing discrete values in intermittent recordings. Although a
      difference was noted when comparing the devices, different fiber separations and
      wavelengths seem then to be of little consequence.

PMID- 16403540
TI  - Restrained eaters show altered brain response to food odor.
AB  - Do restrained and unrestrained eaters differ in their brain response to food
      odor? We addressed this question by examining restrained eaters' brain response
      to food (chocolate) and non-food (geraniol, floral) odors, both when odor was
      attended to and when ignored. Using olfactory event-related potentials (OERPs),
      we found that restrained eaters and controls responded similarly to the non-food
      odor; however, unlike controls, restrained eaters showed no increase in brain
      response to the food odor when they focused attention on it. Rather, restrained
      eaters showed attenuated OERP amplitudes to the food odor in both attended and
      ignored conditions, suggesting that the brain's response to attended food odor
      was abnormally suppressed.

PMID- 16403541
TI  - Effects of sleep deprivation and exercise on cognitive, motor performance and
      mood.
AB  - This study examined the effect of 30 h of sleep deprivation and intermittent
      physical exercise, on both cognitive and psychomotor function as well subjective
      ratings of mood. Six subjects with the following physical characteristics
      participated in the study (Mean +/- S.D.): age 22 +/- 0.3 years, height 180 +/- 5
      cm, body mass: 77 +/- 5 kg, VO2peak 44 +/- 5 ml kg(-1) min(-1). Three subjects
      engaged in normal sedentary activities while three others cycled on a cycle
      ergometer at 50% VO2peak for 20 min out of every 2 h during 30 h of sleep
      deprivation. One week later sleep deprivation was repeated with a cross over of
      subjects. Every 4 h, subjects completed simple and two-choice reaction time tasks
      at both rest and during exercise, a computerized tracking task, a number
      cancellation task, and an assessment of subjective mood state as measured by the
      POMS questionnaire. A 3 x 4 repeated measures ANOVA revealed that resting but not
      exercising reaction times were significantly slower with sleep deprivation. Sleep
      deprivation was also associated with significantly greater negative disturbances
      to subjective vigour, fatigue and depression assessed by the Profile of Mood
      States questionnaire. Compared to those who have been deprived of sleep alone,
      individuals that performed 5 h of intermittent moderate exercise during 30 h of
      sleep deprivation appeared to be more vulnerable to negative mood disturbances
      and impairment in reaction times. This could result in greater risk of accident
      due to a reduced capacity to respond quickly.

PMID- 16403542
TI  - Terpenoids and phenol derivatives from Malva silvestris.
AB  - A sesquiterpene and a tetrahydroxylated acyclic diterpene as well as two known
      monoterpenes, 6 C(13)nor-terpenes and 11 aromatic compounds were isolated from
      the water extract of Malva silvestris. The structures of the compounds were
      determined by spectroscopic NMR and MS analysis. Effects of these compounds on
      germination and growth of dicotyledon Lactuca sativa L. (lettuce) were studied in
      the 10(-4)-10(-7)M concentration range.

PMID- 16403543
TI  - The peroxidative coupling of hemigossypol to (+)- and (-)-gossypol in cottonseed
      extracts.
AB  - Peroxidase(s) present in embryo extracts of Gossypium hirsutum cv. Texas Marker 1
      catalyzed a bimolecular coupling of [4-(3)H]-hemigossypol to [4,4'-(3)H(2)]
      gossypol. The reaction was dependent on the addition of H(2)O(2) and was
      inhibited 71-94% by 1 and 10mM sodium azide. The phenolic coupling produced 53%
      (+)-gossypol and 47% (-)-gossypol in close agreement to the 49% (+)-gossypol and
      51% (-)-gossypol found in the intact seed. The nearly racemic mixture of (+)-and
      (-)-gossypol produced in these embryo extracts can be accounted for by non
      enzymatic random coupling of the free radicals of hemigossypol produced by the
      peroxidase. In contrast, peroxidase reaction mixtures containing crude embryo
      extracts of G. hirsutum var. marie-galante produced 73% (+)-gossypol and 27% (-)
      gossypol. These data from the marie-galante extracts and the fact that these
      intact seed contain 95% (+)-gossypol suggest a regio-stereoselective bimolecular
      coupling of hemigossypol to gossypol. The development of the peroxidative
      coupling of hemigossypol to gossypol in maturing seed of G. hirsutum cv. Texas
      Marker 1 was correlated to the formation of gossypol and suggests that
      peroxidative coupling of hemigossypol contributes to gossypol biosynthesis.

PMID- 16403544
TI  - Simultaneous quantitative LC-ESI-MS/MS analyses of salicylic acid and jasmonic
      acid in crude extracts of Cucumis sativus under biotic stress.
AB  - Salicylic acid (SA) and jasmonic acid (JA) are plant hormones involved in basal
      resistance against plant pathogens and also in induced resistance. The aim of
      this study is to develop a fast and sensitive method to determine simultaneously
      the levels of both these hormones. The present paper proposes a method that
      includes hormone extraction with MeOH-H(2)O-HOAc (90:9:1, v/v), evaporation of
      the extracts, and injection into the liquid chromatography-electrospray
      ionization tandem mass spectrometry (LC-ESI-MS/MS) system in multiple reaction
      monitoring (MRM). Endogenous SA and JA levels in noninfested control cucumber
      cotyledons were 30.96 and 0.73ngg(-1) fresh weight, respectively. In roots, the
      levels were 8.31 and 15.82ngg(-1) FW, respectively. In plants treated with the
      biological control agent Trichoderma asperellum strain T-34, the levels of SA and
      JA did not differ from control plants. Rhizoctonia solani-diseased cucumber
      plants showed higher levels of SA and JA compared to noninfested controls (up to
      2 and 13-fold higher, respectively). Detection limits for SA and JA were 0.45 and
      0.47ngg(-1) fresh weight, respectively. The results of our research include the
      development of a method that is both fast and highly sensitive in the
      simultaneous quantitation of SA and JA from crude cucumber plant extracts,
      avoiding any purification and derivatization steps.

PMID- 16403545
TI  - Characterization of peroxidase in buckwheat seed.
AB  - A peroxidase (POX)-containing fraction was purified from buckwheat seed. The POX
      consisted of two isozymes, POX I and POX II, that were purified 6.6- and 67.4
      fold, respectively. Their molecular weights were estimated to be 46.1 kDa (POX I)
      and 58.1 kDa (POX II) by gel filtration. While POX I and II each oxidized
      quercetin, o-dianisidine, ascorbic acid and guaiacol, only POX II oxidized ABTS.
      Kinetic studies revealed that POX I and II had lower K(m) values for quercetin
      (0.071 and 0.028 mM), ABTS (0.016 mM for POX II) and ascorbic acid (0.043 and
      0.029 mM) than for o-dianisidine (0.229 and 0.137 mM) and guaiacol (0.288 and 0
      ). The optimum pHs of POX I and II for various substrates were almost the same,
      except for quercetin; pH 8.0 for POX I and pH 4.5 for II. Their optimal
      temperatures were 30 degrees C (POX I) and 10 degrees C (POX II), and POX I was
      more stable than POX II above 30 degrees C.

PMID- 16403546
TI  - Local luminance and contrast in natural images.
AB  - Within natural images there is substantial spatial variation in both local
      contrast and local luminance. Understanding the statistics of these variations is
      important for understanding the dynamics of receptive field stimulation that
      occur under natural viewing conditions and for understanding the requirements for
      effective luminance and contrast gain control. Local luminance and contrast were
      measured in a large set of calibrated 12-bit gray-scale natural images, for a
      number of analysis patch sizes. For each image and patch size we measured the
      range of contrast, the range of luminance, the correlation in contrast and
      luminance as a function of the distance between patches, and the correlation
      between contrast and luminance within patches. The same analyses were also
      performed on hand segmented regions containing only "sky", "ground", "foliage",
      or "backlit foliage". Within the typical image, the 95% range (2.5-97.5
      percentile) for both local luminance and local contrast is somewhat greater than
      a factor of 10. The correlation in contrast and the correlation in luminance
      diminish rapidly with distance, and the typical correlation between luminance and
      contrast within patches is small (e.g., -0.2 compared to -0.8 for 1/f noise). We
      show that eye movements are frequently large enough that there will be little
      correlation in the contrast or luminance on a receptive field from one fixation
      to the next, and thus rapid contrast and luminance gain control are essential.
      The low correlation between local luminance and contrast implies that efficient
      contrast gain control mechanisms can operate largely independently of luminance
      gain control mechanisms.

PMID- 16403547
TI  - Melamine-based organoclay to sequester atrazine.
AB  - Sequestration of aqueous atrazine by organoclays prepared from the surfactant 6
      piperazin-1-yl-N,N'-bis-(1,1,3,3-tetramethyl-butyl)-(1,3,5)triazine-2,4-diamine
      and Gonzales bentonite was assessed using 14C-labeled atrazine. Organoclays with
      varying ratios of surfactant to clay were evaluated with respect to their ability
      to sequester atrazine from an aqueous solution. Organoclays containing 100-200 g
      kg-1 surfactant on a total weight basis provided the most efficient adsorption of
      atrazine, with apparent KOC values exceeding 5000 l kg-1 at these loading
      fractions. Less than 12% of sequestered atrazine was released during four
      sequential day long washings, supporting our expectation that the majority of the
      reaction of atrazine with the surfactant lead to irreversible chemical bond
      formation through nucleophilic aromatic substitution.

PMID- 16403548
TI  - Pesticides and metabolites in cassava, eucalyptus, plum and cashew leaves and
      roots in relation to a point source in Kibaha, Tanzania.
AB  - Leaves of Eucalyptus sp., Prunus domestica (plum), and Anacardium occidentale
      (cashew), as well as roots and leaves of Manihot esculenta (cassava) were used to
      study the local distribution of pesticides and metabolites from a point source,
      an old storage site at Vikuge farm in Tanzania. The GPC-cleaned extracts were
      analyzed by GC-ECD and GC/MS. Eleven organochlorine pesticide residues namely
      pentachloroanisole, p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE, p,p'-DDD, o,p'-DDD,
      alpha-HCH, beta-HCH, delta-HCH and epsilon-HCH were detected in the samples. The
      concentrations of total DDT were 818 ng/g fw in Eucalyptus sp., 16 ng/g fw in A.
      occidentale and 4 ng/g fw in P. domestica. In M. esculenta, total DDT ranged from
      191 to 586 ng/g fw in roots and 7 to 425 ng/g fw in leaves. The concentrations of
      total HCH were up to 15 ng/g fw in Eucalyptus sp., while the concentrations of
      pentachloroanisole were up to 2 ng/g fw in leaves of M. esculenta. There are very
      strong positive correlations in the concentrations of the detected compounds,
      suggesting that they have a common source. The low DDE/DDT ratios (0.02-0.07) in
      all samples indicate input of non-degraded DDT from the source. The high alpha
      HCH/gamma-HCH ratios in some samples (>3.1-10) indicate input of technical HCH.
      The concentrations of total DDT in cassava roots were either very close to, or
      greater than, the FAO/WHO limit, indicating risks and concern to public health.

PMID- 16403549
TI  - Statistical evaluation of an analytical IC method for the determination of trace
      level perchlorate.
AB  - Trace level perchlorate analysis in water initiated a new development in the Ion
      Chromatography (IC) technology. Maintenance of a low detection limit may be
      highly affected by the operating conditions of the IC system. In this paper the
      homoscedasticity of the IC system within the calibration concentration range, the
      effect of the system drift on the calibration curve and the effect of the self
      regeneration suppressor (SRS) current on the detection limit were investigated.
      The experimental results were evaluated by statistical methods such as the
      Cochran test and the lack of fit test. The detection limits were obtained by two
      ways. One through method detection limit (MDL) and the other through detection
      limit from the calibration curve (DTC). The Cochran test results revealed the
      homoscedasticity of the IC system. The effect of system drift on the calibration
      curve was noticed by the lack of fit test. MDL yielded a lower but less reliable
      detection limit than DTC. An acceptable detection limit can be achieved under the
      lower SRS current (100 mA).

PMID- 16403550
TI  - Metal accumulation in poplar plant grown with industrial wastes.
AB  - In this study the effects of different levels of industrial wastes on growth
      traits and metal accumulation in aerial portions were determined for
      Populusxeuramericana clone I-214. The experiment started in April 2003. Scions of
      Populusxeuramericana clone I-214, were grown outdoor near Pisa (Italy), in
      lisimeters filled with soil naturally present in the land around the experimental
      site, were daily drip irrigated, hand weeded, monthly fertilized, pruned for a
      unique shoot and cultivated with four increasing treatments: soil non-amended,
      soil amended with 4.8 kgm(-2), with 9.6 kgm(-2) and with 19.2 kgm(-2) of fresh
      tannery waste. The climatic parameters were daily recorded throughout the whole
      experiment. Growth relieves were performed during the growing season. After six
      months since the plantation of the scions, aerial portions of every plant were
      harvested for biomass and metal content analyses. Data demonstrated that the
      waste exerted beneficial effects on poplars mainly through a general increase of
      growth traits and that the nutrients relocation is the mechanisms involved in
      modulating growth rate. The concentration and the amount of the mineral elements
      analysed (N, P, K, Na, Ca, Mg, S, B, Fe, Mn, Cu, Zn, Cr) changed determinately
      among treatments, organs and position. We concluded that phytoremediation
      strategies of tannery wastes might be possible and sustainable for polar
      plantations in soil amended with non-hazardous levels of industrial waste, which
      maintain total heavy metals concentration close to background values.

PMID- 16403551
TI  - An exposure assessment for selected pharmaceuticals within a watershed in
      Southern Ontario.
AB  - Recent studies from a number of countries have shown that measurable
      concentrations of both human and veterinary pharmaceuticals can be found in a
      variety of environmental matrices such as surface and ground water, soils, and
      sediments. Few data are available that characterize the sources, exposure and
      effects of pharmaceuticals in the environment and there is clearly a need to
      define these parameters within a Canadian context. We present in this paper the
      first report in southern Ontario, Canada on the geographic and temporal
      distribution of pharmaceuticals detected within seven tributaries receiving
      primarily agricultural inputs in a typical watershed. Of the 28 pharmaceuticals
      surveyed, 14 were detected in the streams sampled (n=125). Temporal trends in
      concentration for five frequently detected pharmaceuticals show pulses occurring
      between May and November of 2003 at similar but varying times over the seasons,
      depending on the pharmaceuticals, flow rate, and precipitation. Fluctuations in
      concentration of ions indicative of agricultural run off, such as nitrate and
      phosphate, were not found to be useful predictors of changes in pharmaceutical
      concentration (P>0.4), however a significant correlation between dissolved
      organic carbon and monensin and carbamazepine concentrations were observed
      (P<0.013). Exposure profiles illustrating concentration distributions for three
      of the more prevalent pharmaceuticals detected, including lincomycin, monensin
      and carbamazepine, showed a log normal distribution, useful for calculating
      centiles of environmental concentrations. While distributions of estimated total
      potency of pharmaceuticals detected in the surface waters suggested small risks
      of environmental effects of mixtures to daphnia, green algae, Lemna gibba, and
      fish, the significance of non-target effects and impacts due to chronic low level
      exposures to chemical mixtures remains unclear.

PMID- 16403552
TI  - Response of microbial activities to heavy metals in a neutral loamy soil treated
      with biosolid.
AB  - Application of biosolid on land has been widespread in numerous countries for
      last several decades. This study performed incubation experiments by mixing a
      neutral loamy soil and biosolid enriched in Cu, Pb and Zn to explore how heavy
      metal affects soil mineralization and microbial biomass. The experimental results
      indicated that large nutrient, microorganism and C sources from biosolid were
      beneficial to microbial respiration. However, compared to the biosolid alone
      treatment, the supplemented Cu, Pb and Zn in biosolid reduced the mineralized C
      by roughly 36%. This phenomenon was probably caused by a portion of the Cu, Pb
      and Zn being complexed with organic matter to prevent decomposition of organic
      carbon by microorganisms. Equally, soil treated with biosolid increased the
      quantity of mineralized N by approximately five-fold and accelerated the rate of
      N mineralization by about one-fold compared to untreated soil. Notably, addition
      of heavy metals impaired the mineralization process, particularly when Pb reached
      about 64%. The reduced N mineralization occurred for similar reasons to the
      microbial respiration. The addition of biosolid in soil considerably increased
      the amount of mineralizable N; however, the increase was lower in biosolid
      treated soil spiked by heavy metals. The addition of heavy metals in the soil
      biosolid mixture clearly reduced the microbial biomasses C (MBC) and N (MBN),
      indicating that the microbial activities had been disrupted by the heavy metals.
      The microbial biomass C/N ratio had changed initially from 8 to 13 at the end of
      incubation period, owing to various groups of microbes expressing different
      mechanisms of metabolism, indicating that the microbial population had changed
      from bacteria to fungi, which had higher metal tolerance.

PMID- 16403553
TI  - Removal of linear alkylbenzene sulfonates and their degradation intermediates at
      low temperatures during activated sludge treatment.
AB  - The degradation of linear alkylbenzene sulfonates and their degradation
      intermediates (sulfophenylcarboxylic acids) has been characterized at 9 degrees C
      in an activated sludge pilot plant. After an adequate adaptation period (20
      days), LAS primary degradation exceeds 99% and takes place preferentially for
      long alkyl chain homologues and external isomers. LAS homologues in the reactor
      are preferentially sorbed onto particulate matter, while sulfophenylcarboxylic
      acids (SPCs) are present predominantly in solution, due to their lower
      hydrophobicity. During the adaptation period the most abundant LAS biodegradation
      intermediates were long chain sulfophenylcarboxylic acids (SPCs) (C(9)-C(13)SPC).
      However once this system is fully adapted, the microorganisms are capable of
      degrading SPCs efficiently. SPCs with 7-9 carbon atoms in the carboxylic chain
      predominate due to their degradation being slower than for the rest of the SPCs.
      The presence of C(13)SPC confirms that LAS degradation in wastewater starts with
      a omega-oxidation on the alkylic chain. A preferential degradation of SPC isomers
      of the types 2phiC(n)SPC to 6phiC(n)SPC was also detected, as shown by the
      relatively higher SPC concentrations of the remaining ones.

PMID- 16403554
TI  - Pollution sources identification of polycyclic aromatic hydrocarbons of soils in
      Tianjin area, China.
AB  - A total of 188 surface soil samples were collected from different types of
      utilization soils in Tianjin area. Factor analysis and scatter point surface
      tension spine function interpolation were used to analyze types and spatial
      distributions of PAH sources of surface soils in Tianjin area. The results showed
      that most pollution sources were mixed sources including coal burning and
      petroleum spill. Mixed sources occupied 56.12%, 58.96%, 46.45% and 59.50% in
      farmland of wastewater irrigation, common farmland, wild land and city greenbelt,
      respectively. Other pollution sources such as vehicle emission, biogenic
      conversion, wood burning and natural gas combustion were also significant. The
      spatial distributions of pollution sources were closely related to geographic
      location, geographic condition and living habit of indigenes.

PMID- 16403555
TI  - Toxicity of the explosive metabolites hexahydro-1,3,5-trinitroso-1,3,5-triazine
      (TNX) and hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) to the earthworm
      Eisenia fetida.
AB  - Toxicity of hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro
      1,3,5-trinitroso-1,3,5-triazine (TNX) to earthworm was evaluated. Both MNX and
      TNX had lethal and sublethal effects on earthworms. Exposure to MNX- or TNX
      contaminated soil caused a significant concentration-dependent decrease in
      earthworm survival and growth. The lowest observed lethal concentration (LOLC)
      for both MNX and TNX was 100 and 200 mgkg(-1) soil dry weight in the sandy loam
      soil and in the silt loam soil, respectively. No earthworms survived for 14 days
      in MNX- or TNX-spiked soil at 500 mgkg(-1) soil dry weight. After 7 days
      exposure, the lowest observed effect concentration (LOEC) for earthworm growth
      was 50 mgkg(-1) soil dry weight for TNX and 100 mgkg(-1) soil dry weight for MNX
      in both soil types. The LC20 and LC50 for MNX in sandy loam soil were 114 and 262
      mgkg(-1) and for TNX, they were 114 and 254 mgkg(-1) soil dry weight,
      respectively. The corresponding values for MNX and TNX in silt loam soil were 234
      and 390 mgkg(-1) soil dry weight, respectively, and 200 and 362 mgkg(-1) soil dry
      weight, respectively. After 35 days exposure, earthworm growth was reduced 8-39%
      by TNX in sandy loam soil, whereas TNX only inhibited earthworm growth 5-18% at
      the same concentration range in silt loam soil. LC20 and LC50 for TNX were
      slightly lower than for MNX; this indicates that TNX was more toxic than MNX. No
      significant morphological or developmental abnormalities were observed in
      earthworms surviving exposure.

PMID- 16403556
TI  - Heavy metals in coastal water systems. A case study from the northwestern Gulf of
      Thailand.
AB  - A geochemical survey of the northwestern part of the Thailand Gulf (Inner Gulf)
      was carried out in order to define concentrations and distribution patterns of
      selected heavy metals (V, Cr, Co, Ni, Cu, Zn, and U) in the coastal system and
      estuarine area of the Mae Klong river. The results indicate the presence of two
      different sources of heavy metals in the studied environment and allowed us to
      identify a lithogenic component that significantly influences the composition of
      coastal waters and suspended particulate matter (SPM). Comparison of the
      normalized heavy metals concentrations both in the studied samples and in those
      reported for the Sn-W ores present in the surrounding areas suggests an important
      anthropogenic contribution to the chemistry of the seafloor sediments. Vanadium
      and nickel enrichment factors (EF) calculated for coastal waters indicate that
      contamination by hydrocarbons discharge took place in the investigated area.

PMID- 16403557
TI  - Microbial processes in the rhizosphere soil of a heavy metals-contaminated
      Mediterranean salt marsh: a facilitating role of AM fungi.
AB  - We investigated the relationship of the zonal pattern followed by the vegetation
      in a polluted Mediterranean salt marsh, in semiarid south-eastern Spain, with the
      microbiological and biochemical properties (labile C fractions, oxidoreductases
      and hydrolases) of the rhizosphere soil of two halophyte species, Arthrocnemum
      macrostachyum and Sarcocornia fruticosa, and with the degree of arbuscular
      mycorrhizal (AM) colonisation in their rhizospheres. Levels of plant biomass and
      cover were inversely related to heavy metal contents and salinity. The
      concentrations of Fe, Cu, Mn and Pb extracted with DTPA hardly varied among the
      different zones of the salt marsh. The dehydrogenase and phosphatase activities,
      the soluble C and water-soluble carbohydrates concentrations and the extent of
      root colonisation were greater in the salt marsh zones of lower soil salinity and
      lower metal concentration. Urease and beta-glucosidase activities were not
      detected in the salt marsh. Plant biomass and cover showed positive relationships
      with mycorrhizal colonisation (R=0.773, P<0.001; R=0.874, P<0.001, respectively).
      Mycorrhizal colonisation was negatively correlated with the contents of Pb and Zn
      in plant tissues. This work supports the view that reduced plant uptake of toxic
      metals, particularly lead, could be involved in the beneficial effects of AM
      fungi on plant development in Mediterranean salt marshes contaminated with mining
      wastes.

PMID- 16403558
TI  - Accumulation of As, Cd and selected trace elements in tubers of Scirpus maritimus
      L. from Donana marshes (South Spain).
AB  - The collapse of a pyrite-mining, tailing dam on 1998 contaminated an area of 4286
      ha along the Agrio and Guadiamar river valleys in southern Spain. Over 2700 ha of
      the Donana marshes, an important wintering area for wetland European birds, were
      contaminated. This study reports analyses of the tubers of Scirpus maritimus (an
      important food for greylag geese, Anser anser) collected in 2000 in the
      "Entremuros" (spill-affected area) and in nearby unaffected Donana marshes
      (control areas). In the spill-affected area mean tuber tissue concentrations of
      Cd (0.25 mg kg-1) and Zn (61 mg kg-1) were greater than in those tubers from the
      control area (0.02 mg kg-1 for Cd, and 22 mg kg-1 for Zn); values of Cd and Zn in
      "Entremuros" (samples collected two years after the mine spill) were much smaller
      than those reported only a few months after the accident. Trace elements (As, Fe,
      Mn and Tl, and to a lesser extent Cd and Pb) showed a preferential accumulation
      in the outer skin of tubers. Surprisingly, concentrations of As and Fe were
      greater in tubers from some marsh sites not affected by the mine-spill than in
      tubers from the "Entremuros". We suggest that relic river channels within the
      Donana marshes may be contaminated by trace elements from historic mining
      activities. An exhaustive study of macrophytes and other plant species in this
      area is recommended to identify potential risks to wildlife.

PMID- 16403559
TI  - Evaluation of HCH isomers and metabolites in soils, leachates, river water and
      sediments of a highly contaminated area.
AB  - In this work we evaluate the contamination caused by HCH residues in the soil,
      leachates, river water and sediments of an industrial estate of the NW of Spain.
      We study the distribution of the isomers in the different matrices, analysing 37
      soil samples, collected in eight points at several depths, six natural leachates,
      four river water samples and three river sediments. Soil and leachate samples
      present very high levels of HCH isomers, higher than the established by
      legislation, and some pesticides were also detected in the analysed river water
      whereas no pesticides were detected in the river sediments. The distribution of
      isomers was different depending on the matrix analysed. Some natural degradation
      products and also other organochlorine pesticides were detected in the samples
      analysed.

PMID- 16403560
TI  - Chromium adsorption by aligned carbon nanotubes supported ceria nanoparticles.
AB  - Ceria nanoparticles supported on aligned carbon nanotubes (CeO(2)/ACNTs), a novel
      adsorbent for Cr(VI) from drinking water, were prepared by chemical reaction of
      CeCl(3) with NaOH in aligned carbon nanotube solution and subsequent heat
      treatment. The best Cr(VI) adsorption effect of CeO(2)/ACNTs occurs at a pH range
      of 3.0-7.4. The largest adsorption capacity of CeO(2)/ACNTs reaches 30.2 mg g(-1)
      at an equilibrium Cr(VI) concentration of 35.3 mg l(-1) at pH 7.0. The experiment
      results suggest that CeO(2)/ACNTs have great potential applications in
      environmental protection.

PMID- 16403561
TI  - Response of weeping willows to linear alkylbenzene sulfonate.
AB  - Linear alkylbenzene sulfonate (LAS) is the most commonly used anionic surfactant
      in laundry detergents and cleaning agents. LAS compounds are found in surface
      waters and soils. The short-term acute toxicity of LAS to weeping willows (Salix
      babylonica L.) was investigated. Willow cuttings were grown in hydroponic
      solution spiked with LAS at 24.0+/-1 degrees C for 192 h. The normalized relative
      transpiration of plants was used to determine toxicity. Severe reduction of the
      transpiration was only found for high doses of LAS (240 mgl(-1)). Chlorophyll
      contents in leaves of treated plants varied with the dose of LAS, but there was
      no significant linear correlation. The activities of the enzymes superoxide
      dismutases (SOD), catalase (CAT), and peroxidase (POD) were quantified at the end
      of experiments. At higher concentrations of LAS (240 mgl(-1)), the activities of
      SOD and CAT were decreased. The correlation between the dose of LAS and the POD
      activity in leaf cells was the highest of all enzyme assays (R(2)=0.5). EC(50)
      values for a 50% inhibition of the transpiration of the trees were estimated to
      374 mgl(-1) (72 h) and 166 mgl(-1) (192 h). Results from this experiment
      indicated that phytotoxic effects of LAS on willow trees are not expected for
      normal environmental conditions.

PMID- 16403562
TI  - Persistent organic pollution characterization of sediments in Pearl River
      estuary.
AB  - As a byproduct of rapid urbanization and industrial development in the Pearl
      River estuary of South China, excessive release of various types of persistent
      toxic substances were conveyed from agricultural, industrial and municipal
      discharges at upstream section down into the estuary largely via various river
      outlets. In this paper, a persistent organic pollution (POP) characterization of
      sediments in the estuary is undertaken. More than one bioavailable toxicants are
      detected to play active roles in causing toxicity of marine sediments in the
      estuary. POPs may be transported for long distances to the downstream end of the
      Pearl River delta region. The data suggests that DDT might still be applied
      illegally within the region recently and that the prevalent levels of DDTs and
      HCHs in sediments are likely to pose detrimental biological effects on benthic
      organisms. The findings have significant implications in order to understand the
      environmental changes, to determine reasonable ways for future development, and
      to maintain a sustainable environment in the Pearl River estuary region.

PMID- 16403563
TI  - Comparison of efficacy of three extractants to solubilize glomalin on hyphae and
      in soil.
AB  - Glomalin, a glycoprotein produced by arbuscular mycorrhizal (AM) fungi, is a
      major component of the humus fraction of soil organic matter. Glomalin is
      extracted from soil and hyphae of AM fungi by using sodium citrate at 121 degrees
      C in multiple 1-h cycles, but extensive extraction does not solubilize all
      glomalin in all soils. Efficacies of 100 mM sodium salts of citrate, borate or
      pyrophosphate (pH 9.0, 121 degrees C) were tested for two 1-h cycles for hyphae
      from four AM fungal isolates and four 1-h cycles for seven soils from four US
      geographic regions. Residual soil glomalin was examined by pyrophosphate
      extraction of soils previously extracted with citrate or borate followed by
      extraction of all soils after treatment with NaOH. Hyphal extracts were compared
      using Bradford-reactive total protein (BRTP) values, and extracts from soils were
      compared using BRTP, percentage C and C weight. No difference among extractants
      was detected for AM fungal isolates or across soils. The residual glomalin across
      soils for extractants contained the following percentages of the total BRTP:
      pyrophosphate, 14%; borate, 17%; and citrate, 22%. Comparisons among individual
      soils indicated that pyrophosphate extracted significantly more BRTP (10-53%)
      than borate or citrate in six soils and borate was equal to pyrophosphate in one
      soil. Extraction with borate should be compared with pyrophosphate before
      initiating an experiment. For routine extractions of ca. 85% of the glomalin
      across a variety of soils, sodium pyrophosphate appears to be equal to or better
      than borate and better than citrate.

PMID- 16403564
TI  - A study of the partitioning behavior of Irgarol-1051 and its transformation
      products.
AB  - Partitioning behavior of the antifouling booster biocide, Irgarol-1051 (2
      methythio-4-tert-butylamino-6-cyclopropylamino-s-triazine), its production by
      product, M3, and its environmental transformation products, M1 and M2, were
      studied. Octanol-water partition coefficients, log K(OW), and organic matter
      water partition coefficients, log K(OC), of these s-triazines were measured by
      reversed-phase HPLC and a triphasic SPME equilibrium model, respectively. The
      average log K(OW) (+/-SD) of the four s-triazine species were: 4.39+/-0.07 (M3);
      3.38+/-0.12 (Irgarol-1051); 2.92+/-0.12 (M2) and 2.54+/-0.11 (M1), while mean log
      K(OC) (+/-SD) of these species were: 2.47+/-0.03 (M3); 2.16+/-0.03 (Irgarol
      1051); 1.97+/-0.03 (M2) and 1.79+/-0.04 (M1). These results were compared to
      reported physicochemical parameters of Irgarol-1051 in the literature.
      Partitioning behavior of these s-triazine species in the coastal environment
      revealed by their K(OW) and K(OC) were also discussed.

PMID- 16403565
TI  - Performance of the supported copper oxide catalysts for the catalytic
      incineration of aromatic hydrocarbons.
AB  - A fixed bed reactor was used to assess the catalytic incineration of toluene by
      various transition-metal oxide species supported on gamma-Al(2)O(3). CuO/gamma
      Al(2)O(3) was found to be the most active of seven catalysts investigated. The
      CuO species, with a Cu content of 5% (wt), was hence used with four different
      supports (CeO(2), gamma-Al(2)O(3), TiO(2) and V(2)O(5)) in order to define the
      optimal combination. Results of the catalytic incineration of toluene, X-ray
      diffraction (XRD) analysis, oxygen-temperature programmed desorption (O(2)-TPD),
      toluene-temperature programmed desorption (toluene-TPD) and hydrogen-temperature
      programmed reduction (H(2)-TPR) showed that CuO/CeO(2) was the most active
      catalyst, followed by CuO/gamma-Al(2)O(3). The activity of CuO/CeO(2) with
      respect to the VOC molecule was observed to follow this sequence: toluen>p
      xylene>benzene. The addition of water vapor or CO(2) significantly inhibited the
      activity of the CuO/CeO(2) and CuO/gamma-Al(2)O(3) catalysts. The inhibiting
      effect of both was reversible for CuO/gamma-Al(2)O(3). For CuO/CeO(2), the
      inhibiting effect of CO(2) was reversible and even insignificant at a higher
      temperature (220 degrees C), but the effect of H(2)O vapor was somewhat
      irreversible at lower incineration temperatures (220 degrees C). For complete
      oxidation of toluene, the required reaction temperature increased with gas hourly
      space velocity (GHSV) and toluene inlet concentration.

PMID- 16403566
TI  - On the uniqueness of humankind: is language working memory the final piece that
      made us human?

PMID- 16403567
TI  - CYP1A1 gene polymorphism as a risk factor for cervical intraepithelial neoplasia
      and invasive cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of CYP1A1*3 gene
      polymorphism in the development of cervical cancer by comparing patients having
      cervical intraepithelial neoplasia (CIN) or invasive cervical cancer with control
      subjects. METHODS: CYP1A1*3 polymorphism was analyzed using an allele-specific
      PCR-based method. RESULTS: In the group of patients with CIN, the frequency of
      the Ile/Val and of any Val alleles was significantly higher than in the healthy
      control subjects (OR: 4.51; 95%CI = 2.42-8.43, and OR: 3.71; 95%CI = 2.03-6.78).
      In the CIN1 group, patients with Ile/Val and any Val genotypes were found to be
      significantly higher (OR: 10.53; 95%CI = 3.78-29.33 and OR: 8.38; 95%CI = 3.04
      23.08). In the CIN2 group, patients with Ile/Val and any Val revealed a 4.06- and
      3.23-fold higher risk than those with Ile/Ile (95%CI = 1.54-10.74 and 1.24-8.45).
      However, the variance in the group of patients with CIN3 did not reach
      statistical significance. Patients with cervical cancer were analyzed with
      respect to the histological diagnoses. In the adenocancer group, the estimated
      ORs with respect to the control subjects were 11.29 for Ile/Val (95%CI = 3.35
      38.07) and 8.98 for any Val groups (95%CI = 2.69-30.01), with a statistical
      significance. Among the squamous cell cancer patients, Ile/Val and any Val were
      significantly higher than in controls (OR: 5.76; 95%CI = 3.13-10.59 and OR: 5.20;
      95%CI = 2.91-9.28). Although Val/Val genotype did not reach a significant value,
      it was near significance with an OR of 3.03 (95%CI = 0.95-9.68). CONCLUSION:
      These results suggest that CYP1A1*3 gene polymorphism is linked to a propensity
      for cervical carcinogenesis and further series are needed to detect the exact
      role of this unique variation.

PMID- 16403568
TI  - Bilateral sclerosing stromal tumor of the ovaries in a premenarchal girl.
AB  - BACKGROUND: Sclerosing stromal tumor of the ovary is a rare benign neoplasm that
      is usually unilateral in menstruating women with a mean age of 27. CASE: An 11
      year-old girl presented with asymptomatic bilateral sclerosing stromal tumor of
      the ovaries prior to menarche. We describe the clinical, radiologic and
      histologic findings with reference to other reported cases. CONCLUSION: We herein
      report a unique case of bilateral sclerosing stromal tumor of the ovaries arising
      in a premenarchal girl.

PMID- 16403569
TI  - Biomarker discovery for ovarian cancer using SELDI-TOF-MS.
AB  - OBJECTIVES: The purpose of this study is to discover potential biomarkers for the
      detection and monitoring of adjuvant chemotherapy for ovarian cancer. METHODS:
      Serum samples from ovarian cancers and non-cancer controls were analyzed using
      surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
      (SELDI-TOF-MS). To discover the possible diagnostic biomarker for ovarian cancer,
      a preliminary training set of spectra derived from 31 primary ovarian cancer
      patients, 16 patients with benign ovarian diseases, and 25 healthy women was used
      to develop a proteomic model that discriminated cancer from non-cancer
      effectively. A blind test set, including 43 new cases, was used to validate the
      sensitivity and specificity of this multivariate model. To explore treatment
      induced serum protein change, the protein profiles generated from 16
      postoperative patients before chemotherapy are compared with those obtained after
      chemotherapy. RESULTS: A Four-peak model was established in the training set that
      discriminated cancer from non-cancer with sensitivity of 90.8% and specificity of
      93.5%. A sensitivity of 87.0% and a specificity of 95.0% for the blind test were
      obtained, compared with 60.7%, 55% for CA125 for the same samples. These 4
      markers performed significantly better than the current standard marker, CA125 (P
      < 0.05). One protein peak (mass/charge ratio [m/z], 4,475) was identified in 12
      of 16 (75%) postoperative patients after chemotherapy, but was absent before
      chemotherapy. CONCLUSION: The proteins represented by these peaks are candidate
      biomarkers for ovarian cancer diagnosis and/or monitoring treatment response.

PMID- 16403570
TI  - The antinociceptive effects of the systemic adenosine A1 receptor agonist CPA in
      the absence and in the presence of spinal cord sensitization.
AB  - Adenosine A1 receptor agonists are effective antinociceptive agents in
      neuropathic and inflammatory pain, though they appear to be weak analgesics in
      acute nociception. Important discrepancies are observed on the effectiveness and
      potency of adenosine analogues when comparing different studies, probably due to
      the use of different ligands, models of antinociception, routes of administration
      and types of sensitization. We studied the systemic antinociceptive effects of
      the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) in spinal cord
      neuronal responses from adult male rats in acute nociception and in sensitization
      due to arthritis and neuropathy. The experiments showed that CPA was effective in
      the three experimental conditions, with a similar potency in reducing responses
      to noxious mechanical stimulation (ID50s: 20 +/- 1.2 microg/kg in acute
      nociception, 18 +/- 1.1 microg/kg in arthritis, 17.4 +/- 2 microg/kg in
      neuropathy). The phenomenon of wind-up was also dose-dependently reduced by CPA
      in the three experimental situations although the main action was seen in
      arthritis. Depression of blood pressure by CPA was not dose-dependent. We
      conclude that systemic CPA is a potent and effective analgesic in sensitization
      due to arthritis and neuropathy but also in acute nociception. The effect is
      independent of the cardiovascular activity and is centrally mediated since wind
      up was inhibited.

PMID- 16403571
TI  - Do films about mentally disturbed characters promote ineffective coping in
      vulnerable youth?
AB  - Suicidal youth tend to doubt the effectiveness of professional mental health
      treatment. This study examined whether exposure to films about suicidal and
      mentally disturbed persons supports this lack of belief. Exposure to three
      popular films featuring suicides or the mentally ill was compared to films that
      featured a heroic suicide unrelated to mental illness as well as to films with
      violent and comedic content in a nationally representative survey of youth ages
      14-22 (N=900). Exposure to films about mental disturbance among "vulnerable"
      respondents who had experienced recent depressive and suicidal symptoms (24% of
      sample) was compared to those without these symptoms. Increasing exposure to
      films with mentally disturbed characters was related to belief in the treatment
      inefficacy of mental disorders. The findings suggest that exposure to fictional
      depictions of characters failing to get help for mental disorders may have long
      term effects on depressed and suicidal youth.

PMID- 16403572
TI  - 31P NMR and isothermal titration calorimetry studies on polyoxomolybdates
      catalyzed hydrolysis of ATP.
AB  - ATP hydrolysis in the presence of polyoxomolybdates at pH levels of 6, 4, and 2
      has been investigated with a help of high pressure liquid chromatography (HPLC)
      analyses, 31P- and 1H NMR measurements, and isothermal titration calorimetry
      (ITC). The polyoxomolybdates-induced ATP-hydrolysis proceeded satisfactorily in
      pH < 6 media at 20 degrees C with an optimum pH level of 4, while it was
      significantly depressed at low temperature of < or = 5 degrees C. At pH levels of
      6 and 4, ADP was a main product, and the involvement of [(PO4)2Mo5O15](6-)-like
      ATP-molybdate complex as an intermediate was implied. At pH 2 ATP was decomposed
      to AMP with small generation of ADP through the formation of the ATP-molybdate
      complex isostructural with [(O3POPO3)Mo6O18(H2O)4]4- as an intermediate. The ITC
      result at pH 4 showed an occurrence of two types of the exothermic binding
      reactions between molybdate and ATP with binding constants (K) of 6.61x10(4) and
      9.40x10(3) M(-1) and molar enthalpy values (deltaH) of -6.32x10(4) and 
      4.73x10(3) J mol(-1), respectively. Together with the results of 1H NMR
      measurements, it is deduced that the molybdates interact with not only phosphate
      sites in the ATP side-chain, but also adenine-ring with an accompanying
      aggregation of molybdates at pH 4.

PMID- 16403574
TI  - Low spin states of microperoxidases produced by inter- and intra-peptide chain
      sixth ligands: effect of pH and the oligopeptide type.
AB  - The low spin states of microperoxidases (MP)-8, -9 and -9 N-acetylated (N-Ac)
      were characterized using UV-visible, circular dichroism, and electron
      paramagnetic resonance spectroscopies over the 6.0-12.0 pH range. The first MP-8
      alkaline transition (pK(a)=8.53) produced hemepeptide aggregates in the low spin
      state in which a water molecule was replaced by the peptide chain N-terminal
      group of a neighboring MP-8 molecule. Higher pH led to the deprotonation of the
      MP-8 histidine imidazole ring (pK(a)=10.37) at the fifth coordination position.
      This MP-8 species was in equilibrium with a high spin state aggregate in which
      OH(-) replaced histidinate, the histidinate becoming the heme iron sixth ligand
      in a neighboring MP-8 molecule. In a similar way to the N-AcMP-8, the low spin
      state of N-AcMP-9 was produced by the deprotonation of the water molecule
      (pK(a)=9.6) situated at the sixth coordination position of the heme iron. Up to
      pH 8.5, the low spin states of MP-9 were aggregates in which the alpha-amino
      group of Lys13 replaced water at the sixth coordination position of a neighboring
      MP-9 molecule. Above pH 8.5, the epsilon-amino groups of Lys13 established intra
      chain coordination and impaired the formation of aggregates. Such intra-chain
      interaction in MP9 was supported by molecular dynamics simulation. These MP-9
      monomers might also exhibit OH(-) or histidinate at the fifth coordination
      position.

PMID- 16403573
TI  - The role of Thr268 and Phe393 in cytochrome P450 BM3.
AB  - In flavocytochrome P450 BM3 there are several active site residues that are
      highly conserved throughout the P450 superfamily. Of these, a phenylalanine
      (Phe393) has been shown to modulate heme reduction potential through interactions
      with the implicitly conserved heme-ligand cysteine. In addition, a distal
      threonine (Thr268) has been implicated in a variety of roles including proton
      donation, oxygen activation and substrate recognition. Substrate binding in P450
      BM3 causes a shift in the spin state from low- to high-spin. This change in spin
      state is accompanied by a positive shift in the reduction potential (DeltaE(m)
      [WT+arachidonate (120 microM)]=+138 mV). Substitution of Thr268 by an alanine or
      asparagine residue causes a significant decrease in the ability of the enzyme to
      generate the high-spin complex via substrate binding and consequently leads to a
      decrease in the substrate-induced potential shift (DeltaE(m) [T268A+arachidonate
      (120 microM)]=+73 mV, DeltaE(m) [T268N+arachidonate (120 microM)]=+9 mV). Rate
      constants for the first electron transfer and for oxy-ferrous decay were measured
      by pre-steady-state stopped-flow kinetics and found to be almost entirely
      dependant on the heme reduction potential. More positive reduction potentials
      lead to enhanced rate constants for heme reduction and more stable oxy-ferrous
      species. In addition, substitutions of the threonine lead to an increase in the
      production of hydrogen peroxide in preference to hydroxylated product. These
      results suggest an important role for this active site threonine in substrate
      recognition and in maintaining an efficiently functioning enzyme. However, the
      dependence of the rate constants for oxy-ferrous decay on reduction potential
      raises some questions as to the importance of Thr268 in iron-oxo stabilisation.

PMID- 16403575
TI  - Pneumocystis pneumonia--a retrospective study 1991-2001 in Gothenburg, Sweden.
AB  - OBJECTIVES: Pneumocystis pneumonia (PCP) is a severe opportunistic infection in
      immunosuppressed patients, caused by Pneumocystis jiroveci. The incidence among
      HIV negative patients is considered to have increased during the last decade.
      METHODS: We collected data retrospectively from the cases with PCP diagnosed at
      Sahlgrenska University Hospital between January 1991 and December 2001. RESULTS:
      118 episodes of PCP were registered in 108 patients. The most common underlying
      immunosuppressions were HIV and solid organ transplantation with 29 and 26 cases,
      respectively. The number of PCP cases did not increase during the study period.
      Out of the 118 episodes of PCP 89 (75%) were in patients not infected with HIV.
      No clusters were found among HIV positive patients. We found 5 smaller clusters
      among non-HIV patients. Among the cases with proven PCP, 17% were on prophylaxis:
      30% of the HIV infected patients and 13% of the non-HIV patients. CONCLUSIONS:
      The number of PCP cases is not increasing, 75% of the patients are HIV negative,
      Only 17% of the patients were on prophylaxis before the episode of PCP,
      indicating that not all patients at risk are identified.

PMID- 16403577
TI  - Systemic inflammatory response syndrome in adult patients with nosocomial
      bloodstream infection due to Pseudomonas aeruginosa.

PMID- 16403576
TI  - Bloodstream infections in organ transplant recipients receiving alemtuzumab: no
      evidence of occurrence of organisms typically associated with profound T cell
      depletion.
AB  - BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed against CD52,
      a cell surface antigen expressed on B and T lymphocytes, monocytes and NK cells.
      Its use results in a profound decrease in CD4 positive T lymphocytes. Alemtuzumab
      is used as induction immunosuppression and therapy for rejection in organ
      transplant recipients in some centers. We followed a cohort of 449 consecutive
      transplant recipients who received alemtuzumab to determine the occurrence of
      bloodstream infections, particularly those previously associated with decrease in
      CD4 positive T lymphocytes. PATIENTS AND METHODS: Fifteen percent (69/449)
      patients had at least one episode of bloodstream infection. However, no patient
      had bacteremia with Streptococcus pneumoniae, Listeria monocytogenes, non
      typhoidal Salmonella or Mycobacterium avium complex. Fungaemia was rare,
      occurring in 1.5% of patients. The most common organisms isolated from the blood
      were Staphylococcus aureus (21 episodes), coagulase negative Staphylococcus (14
      episodes), Klebsiella pneumoniae (12 episodes), Enterococcus faecium (11
      episodes), Pseudomonas aeruginosa (10 episodes), Enterococcus faecalis (9
      episodes) and Escherichia coli (7 episodes). DISCUSSION: We conclude that
      although alemtuzumab use is associated with profound CD4 positive T lymphocyte
      depletion, alemtuzumab does not seem to be associated with an increased risk of
      bloodstream infection with pathogens typically seen in other disorders of CD4
      cell depletion, such as acquired immunodeficiency syndrome.

PMID- 16403578
TI  - Pneumonia and bacteremia due to Serratia odorifera.

PMID- 16403579
TI  - Mycobacterium mucogenicum sepsis in an immunocompetent patient.
AB  - We report a case of Mycobacterium mucogenicum sepsis in an immunocompetent woman
      with Munchausen syndrome presenting with multiple abscesses.

PMID- 16403581
TI  - Pneumocystis pneumonia revisited: delayed diagnosis in an HIV infected individual
      with high blood and low lung CD4 T cell counts.
AB  - The peripheral blood CD4 count is a useful marker of immunological status in HIV
      infection. However, it makes up only 1% of total body CD4 cells [Parslow T.
      Lymphocytes and lymphoid tissue. In: Stites D, Terr A, Parslow D, editors. Basic
      and clinical immunology. Appleton and Lange; 1994. p. 22-40.] has a wide intra-
      and inter-individual variability [Turner BJ, Hecht FM, Ismail RB. CD4+ T
      lymphocyte measures in the treatment of individuals infected with human
      immunodeficiency virus type 1. A review for clinical practitioners. Arch Intern
      Med 1994;154:1561-73.] and CD4 cell pathology is just one of the immune defects
      caused by HIV [Fauci S. Multifactorial nature of human immunodeficiency virus
      disease. Science 1993;262:1011-8.]. Thus a given value should always be
      interpreted within a specific clinical context. We describe an individual with
      Pneumocystis pneumonia (PCP) who was reviewed by HIV medical services several
      times before the correct diagnosis was made. On each occasion the possibility of
      PCP was discounted as he had a well-preserved blood CD4 count. Subsequent
      examination of his pulmonary T-lymphocyte subsets revealed marked CD4
      lymphopenia.

PMID- 16403580
TI  - Three fatal cases of invasive serotype VI group B streptococcal infection.
AB  - Serotype VI group B Streptococcus (GBS) has been almost frequently isolated among
      colonizing strains of pregnant women in Japan, but the clinical features and
      prognosis, when a patient is invasively infected, are largely unknown. We report,
      for the first time, three cases of fatal infection caused by serotype VI GBS; two
      cases were middle-aged men with necrotizing fasciitis/cellulitis, sepsis, and
      toxic shock syndrome with poorly controlled diabetes as underlying conditions;
      and one was a premature infant with intrauterine infection. Our results indicated
      that type VI GBS is pathogenic for humans not only in fetuses but also adults,
      and has the ability to be fatal, at least in selected patients.

PMID- 16403582
TI  - The combined use of esophageal electrocardiogram and multiple right parasternal
      chest leads in the diagnosis of PSVT and determination of accessory pathways
      involved: a new simple noninvasive approach.
AB  - INTRODUCTION: Paroxysmal Supraventricular Tachycardia (PSVT) resulting from any
      cause can at times lead to diagnostic difficulty mainly when due to AVNRT and
      AVRT. In this study we used a non-invasive approach using esophageal ECG (ECGe)
      and ECG derived from the various right parasternal chest leads (RPCL) to
      correctly diagnose the type of PSVT as well the accessory pathways involved in
      AVRT. METHODS AND RESULTS: We studied a total of 161 patients (89 male) all
      having a history of palpitation. All the patients underwent routine 12 lead ECG,
      ECGe, RPCL and electrophysiologic study. With use of ECGe and RPCL, 71 (44.1%)
      were diagnosed as having AVNRT and 90 (55.9%) having AVRT with various accessory
      pathways compared to only 49 (30.4%) and 22 (13.7%) respectively with routine 12
      lead ECG. With combined ECGe and RPCL, 80 (49.7%) showed accessory pathway in the
      left free wall, 4 (2.5%) showed in the right free wall, 6 (3.7%) septal accessory
      pathway, 60 (37.3%) in the anterior wall and 30 (18.6%) in the posterior wall. In
      comparison, EPS could show accessory pathways in the left free wall in 81
      (50.3%), in the right free wall in 5 (3.1%), in the septum in 4 (2.5%), in the
      anterior wall in 53 (32.9%) and in the posterior wall in 37 (23.0%) out of the
      161 patients. CONCLUSIONS: ECGe+RPCL can be used as a reliable noninvasive
      diagnostic tool to identify the nature of tachycardia and the pathways involved
      in the reentrant ring of PSVT especially in those with multiple atrioventricular
      accessory pathways or a combination of atrioventricular accessory pathways and
      dual atrioventricular nodal pathway.

PMID- 16403583
TI  - Conversion of atriopulmonary Fontan to extracardiac total cavopulmonary
      connection improves cardiopulmonary function.
AB  - BACKGROUND: Experimental studies showed that extracardiac total cavopulmonary
      connection provides superior hemodynamics than atriopulmonary Fontan. METHODS: We
      prospectively assessed the impact of conversion of atriopulmonary Fontan to
      extracardiac total cavopulmonary connection on exercise capacity and cardiac
      function in 6 consecutive patients. RESULTS: Six months after conversion to
      extracardiac total cavopulmonary connection, we observed an increase in peak
      oxygen uptake in all patients (p=0.01;+17%). This improvement was associated to
      an increase of peak O(2) pulse (p=0.01;+16%), but no change in peak heart rate,
      arterial oxygen saturation at peak exercise, and pulmonary function. Ventricular
      ejection fraction did not change significantly after surgery. Conversion was
      associated with an improvement in heart failure symptoms as assessed by the New
      York Heart Association classification. Patients who had undergone additional anti
      arrhythmia surgery for atrial fibrillation had no recurrence of arrhythmia at
      follow-up. CONCLUSION: Data indicate that conversion to extracardiac total
      cavopulmonary connection is associated with an improvement of cardiopulmonary
      function and heart failure symptoms. Improved exercise capacity is due to an
      increase in O(2) pulse and may reflect an improved cardiac stroke volume after
      the operation.

PMID- 16403584
TI  - Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts
      and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D
      dose volume parameters and aspects of 3D image-based anatomy, radiation physics,
      radiobiology.
AB  - The second part of the GYN GEC ESTRO working group recommendations is focused on
      3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and
      parameters have been developed and validated from dosimetric, imaging and
      clinical experience from different institutions (University of Vienna, IGR Paris,
      University of Leuven). Cumulative dose volume histograms (DVH) are recommended
      for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV
      and IR CTV are the minimum dose delivered to 90 and 100% of the respective
      volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed
      dose (V150, V200), is recommended for overall assessment of high dose volumes.
      V100 is recommended for quality assessment only within a given treatment
      schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue
      volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3.
      Underlying assumptions are: full dose of external beam therapy in the volume of
      interest, identical location during fractionated brachytherapy, contiguous
      volumes and contouring of organ walls for >2 cm3. Dose values are reported as
      absorbed dose and also taking into account different dose rates. The linear
      quadratic radiobiological model-equivalent dose (EQD2)-is applied for
      brachytherapy and is also used for calculating dose from external beam therapy.
      This formalism allows systematic assessment within one patient, one centre and
      comparison between different centres with analysis of dose volume relations for
      GTV, CTV, and OAR. Recommendations for the transition period from traditional to
      3D image-based cervix cancer brachytherapy are formulated. Supplementary data
      (available in the electronic version of this paper) deals with aspects of 3D
      imaging, radiation physics, radiation biology, dose at reference points and
      dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, Potter R,
      Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO
      Working Group (I): concepts and terms in 3D image-based 3D treatment planning in
      cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV.
      Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio
      including target coverage and sparing of organs at risk can be significantly
      improved, if radiation dose is prescribed to a 3D image-based CTV taking into
      account dose volume constraints for OAR. However, prospective use of these
      recommendations in the clinical context is warranted, to further explore and
      develop the potential of 3D image-based cervix cancer brachytherapy.

PMID- 16403586
TI  - Expression and purification of a fusion-typed pediocin PA-1 in Escherichia coli
      and recovery of biologically active pediocin PA-1.
AB  - Pediocin PA-1 is a representative class IIa bacteriocin which is small and heat
      stable and has a consensus motif, -YGNGV-. The plasmid pQE40PED, encoding
      pediocin PA-1 fused with His-tagged mouse dihydrofolate reductase (DHFR), was
      constructed and introduced into Escherichia coli M15 strain. The fusion protein
      was overexpressed in the strain after induction of isopropyl-beta-D
      thiogalactopyranoside (IPTG) and purified by nickel-nitrilotriacetic acid (Ni
      NTA) metal affinity chromatography. For the recovery of biologically active
      pediocin PA-1, the purified fusion protein was cleaved by Factor Xa protease and
      the liberated pediocin PA-1 was finally purified by ultrafiltration with a 75%
      yield. The molecular mass of the purified recombinant pediocin PA-1 was the same
      as that of native pediocin PA-1 on an electrophoresis gel.

PMID- 16403587
TI  - On modeling and simulating transitions between microbial growth and inactivation
      or vice versa.
AB  - Resumed growth of the survivors of a heat or chemical treatment after cooling or
      a disinfectant dissipation is not an uncommon phenomenon. Similarly, the inverse,
      the onset of mortality in a growing microbial population as a result of exposure
      to increasing temperature or concentration of an antimicrobial agent, is also a
      familiar scenario. Provided that in either regime, the organism has no time to
      adapt biologically, the continuous transition from growth to inactivation or vice
      versa can be simulated with conventional growth and inactivation models, whose
      rate constant is allowed to change sign. Where both the growth and inactivation
      follow first-order kinetics, the sign change has no effect on the model
      equation's solutions. The same applies when the growth and inactivation patterns
      are described by a rate model, like the differential logistic equation or its
      various variants. However, determination of such models' coefficients from
      experimental isothermal growth and inactivation data can be difficult for
      technical reasons, unless the model can be integrated analytically. If not, or
      when the model itself is unknown a priori, then the rate equation would have to
      be derived from the fit of empirical models like the Weibull, modified versions
      of the logistic function and the like. But this may create a new kind of problem
      as a result of that the log and certain power operations cannot be used for
      negative numbers. For certain models at least, the problem can be solved through
      modification of the procedure by which the rate equation is solved numerically.
      This is demonstrated in simulated transitions between growth and inactivation and
      between inactivation and growth based on the log linear and Weibullian-power law
      models and three logistic patterns based on a shifted logistic function, the
      Baranyi-Roberts model and a shifted arctan model.

PMID- 16403585
TI  - Skin conductance responses are elicited by the airway sensory effects of puffs
      from cigarettes.
AB  - The airway sensations stimulated by smoking are an important source of hedonic
      impact (pleasure) for dependent smokers. The learning process by which these
      sensations become pleasurable is not well understood. The classical conditioning
      model predicts that airway sensory stimulation will elicit sympathetic arousal
      that is positively correlated with the hedonic impact that is elicited by airway
      sensory stimulation. To test this prediction, we measured skin conductance
      responses (SCRs) and subjective hedonic impact elicited by a series of individual
      puffs from nicotinized, denicotinized and unlit cigarettes. Nicotinized puffs
      elicited more subjective hedonic impact than denicotinized and unlit puffs partly
      as a result of the fact that they provided a greater level of airway sensory
      stimulation. We found that SCRs were not larger for nicotinized puffs than for
      denicotinized puffs, but that they were larger for both nicotinized and
      denicotinized puffs than for unlit puffs. We also found that the average SCR of a
      subject to denicotinized puffs was positively correlated with the average hedonic
      impact that a subject obtained from denicotinized puffs. Together, this suggests
      that SCR magnitude does not reflect within-subject variations in hedonic impact
      that are due to variations in the level of airway sensory stimulation, but that
      it does reflect individual differences in the amount of hedonic impact that is
      derived from a given level of airway sensory stimulation. The results of a post
      hoc correlation analysis suggest that these individual differences may have been
      due to variations in the prevailing urge to smoke. The implications of these
      findings for the classical conditioning model, as well as for other learning
      models, are discussed.

PMID- 16403588
TI  - Gastroretentive dosage forms: overview and special case of Helicobacter pylori.
AB  - The challenge to develop efficient gastroretentive dosage forms began about 20
      years ago, following the discovery of Helicobacter pylori by Warren and Marshall.
      In order to understand the real difficulty of increasing the gastric residence
      time of a dosage form, we have first summarized the important physiologic
      parameters, which act upon the gastric residence time. Afterwards, we have
      reviewed the different drug delivery systems designed until now, i.e. high
      density, intragastric floating, expandable, superporous hydrogel, mucoadhesive
      and magnetic systems. Finally, we have focused on gastroretentive dosage forms
      especially designed against H. pylori, including specific targeting systems
      against this bacterium.

PMID- 16403589
TI  - Gene-for-gene-mediated recognition of nuclear-targeted AvrBs3-like bacterial
      effector proteins.
AB  - Plant disease resistance (R) genes mediate specific recognition of pathogens via
      perception of cognate avirulence (avr) gene products. The numerous highly similar
      AvrBs3-like proteins from the bacterial genus Xanthomonas provide together with
      their corresponding R proteins a unique biological resource to dissect the
      molecular basis of recognition specificity. A central question in this context is
      if R proteins that mediate recognition of structurally similar Avr proteins are
      themselves functionally similar or rather dissimilar. The recent isolation of
      rice xa5, rice Xa27 and tomato Bs4, R genes that collectively mediate recognition
      of avrBs3-like genes, provides a first clue to the molecular mechanisms that
      plants employ to detect AvrBs3-like proteins. Their initial characterization
      suggests that these R proteins are structurally and functionally surprisingly
      diverge. This review summarizes the current knowledge on R-protein-mediated
      recognition of AvrBs3-like proteins and provides working models on how
      recognition is achieved at the molecular level.

PMID- 16403590
TI  - QSAR study of 4-phenylpiperidine derivatives as mu opioid agonists by neural
      network method.
AB  - A nonlinear QSAR study was conducted on a series of 4-phenylpiperidine
      derivatives (4PPs) acting as mu opioid agonists by three-layer back-propagation
      neural network (NN) method. At first a variety of molecular descriptors were
      calculated and then selected with two-stage least squares combining partial least
      squares (PLS) method. The selected four molecular descriptors, out of 292 ones,
      were correlated with the known analgesic activities of 38 4PPs by NN method. The
      established QSAR model was further validated by five additional 4PPs, as an
      external testing set. Moreover, a pharmacophore model was hypothesized based on
      the results, which would be helpful for structural optimization of 4PPs.

PMID- 16403591
TI  - Baccalaureate nursing students' breastfeeding knowledge: a descriptive survey.
AB  - This descriptive survey study assessed the breastfeeding knowledge of junior and
      senior baccalaureate nursing students (N=80) who had successfully completed their
      obstetric nursing course. With a possible perfect knowledge score of 100,
      participants' scores ranged from 35 to 85 with a sample mean score of 60.
      Surprisingly, most (85%) did not know that breastfeeding is recommended for the
      first year of an infant's life, and only five participants knew the proper
      management of mastitis. Well over one third (41.3%) of the participants opposed
      breastfeeding in public. Findings reveal the need to strengthen both the didactic
      and clinical components of the obstetric course curriculum. The acquisition of
      breastfeeding knowledge at the student level will better equip novice nurses to
      provide more effective breastfeeding counsel and support for childbearing women
      and to promote the achievement of the breastfeeding objectives of both the United
      States and the World Health Organization.

PMID- 16403592
TI  - Catalytic amounts of fructose may improve glucose tolerance in subjects with
      uncontrolled non-insulin-dependent diabetes.
AB  - BACKGROUND: It was suggested that acute ingestion of small amounts of fructose
      can improve glucose homeostasis. AIM: To study the effect of a long-term tri
      daily supplementation of catalytic amounts of fructose on glucose tolerance of
      subjects with type 2 diabetes (NIDDM). METHODS: A double-blind, placebo
      controlled study. Twenty-six subjects with uncontrolled NIDDM as indicated by
      high levels of hemoglobin A1C (Hgb(A1c)) and 2-h postprandial glucose levels >200
      mg% were assigned to either fructose or maltodextrin supplementation (7.5 g) tri
      daily after each main meal. The subjects were challenged with a fixed meal and
      blood was drawn for determining levels of glucose, insulin and triglycerides
      before and 2 h after meal at baseline and 1 month after study entry. Blood was
      drawn for total cholesterol, high-density and low-density lipoprotein cholesterol
      (LDL-c), fructosamine and Hgb(A1C) before study entry and at 1, 2 and 3 months
      into the study. RESULTS: No changes were observed in the difference between
      postprandial and pre-meal glucose, insulin or triglyceride levels in each group
      or between groups. No significant statistical differences were found in weight,
      total cholesterol, LDL-c and high-density lipoprotein cholesterol (HDL-c) in each
      group or between groups along the study period. After 1 month fructosamin levels
      decreased in the fructose-supplemented group but not in the maltodextrin
      supplemented group (P<0.052). Hgb(A1C) levels decreased with time in both groups
      but were significantly lower at 2 months in the fructose group as compared to the
      maltodextrin group (P<0.03). CONCLUSIONS: Subjects with NIDDM may benefit from
      daily supplementation of catalytic amounts of fructose in their diet.

PMID- 16403593
TI  - Distribution and migration of 95Zr in a tea plant/soil system.
AB  - (95)Zr is a primary radionuclide in the radioactive liquid efflux from a
      pressurized water reactor and one of the main radionuclides released after
      nuclear accidents. The fission yield of (95)Zr is as high as 6.2%, however, its
      environmental behavior has not been well documented. An experiment was conducted
      to evaluate the accumulation and distribution of (95)Zr in a tea plant/soil
      system. (95)Zr was accumulated primarily in the trunk of tea plants after being
      taken up from the soil. The radioactivity concentration of (95)Zr in the trunk
      increased slowly with time, then it reached a dynamic equilibrium 14 days after
      application. The radioactivity concentration of (95)Zr in the other parts of the
      tea plant was very low; only slighter greater than the detection limit. The
      results indicated that (95)Zr was not readily translocated in the tea plant.
      About 98.9% of applied (95)Zr was found to concentrate in the upper 5 cm layer
      after being sprayed onto the soil surface. The results indicated that (95)Zr
      could not readily move downwards with percolating water due to strong adsorption
      to surface soil.

PMID- 16403594
TI  - Reliability of concentric and eccentric torque during isokinetic knee extension
      in post-stroke hemiparesis.
AB  - BACKGROUND: Emerging evidence on the velocity-dependent nature of force
      impairment in post-stroke hemiparesis has emphasized the complexity of strength
      and motor performance assessments in this clinical population. The need to
      establish reliability and responsiveness of muscle performance measures across a
      broad range of concentric and eccentric movement speeds is therefore clear, as
      these metrics will provide benchmarks both for making clinical inference and
      evaluating meaningful clinical change following interventions. METHODS:
      Isokinetic knee extensor strength was tested at 14 angular velocities in 17
      adults with chronic post-stroke hemiparesis (>18 months), and 13 non-disabled
      controls. Identical tests were conducted on two occasions separated by two days.
      Test-retest reliability of maximal isokinetic torque was evaluated using
      intraclass correlation. Absolute reliability was assessed using standard error of
      measurement from which smallest real differences were derived. FINDINGS: Overall,
      intraclass correlation coefficients were excellent for both hemiparetic (0.891)
      and control (0.937) groups. Intraclass correlation coefficients for each
      criterion speed were also high for both groups (>0.86). Measurement error
      relative to the mean torque varied between 14.1% and 26.3% for hemiparetic
      subjects and 6.0-18.1% for controls. The smallest real difference relative to
      mean torque was 39.0-72.7% and 16.6-50.2% for hemiparetic and control subjects,
      respectively. INTERPRETATION: Isokinetic knee extension torque can be measured
      reliably in persons with chronic post-stroke hemiparesis and in non-disabled
      controls across a full functional range of concentric and eccentric speeds.
      Established measurement error and smallest real differences will aid
      interpretation of longitudinal observations of muscle performance in this
      clinical population.

PMID- 16403595
TI  - "I thought it was only ordinary fever!" cultural knowledge and the micropolitics
      of therapy seeking for childhood febrile illness in Tanzania.
AB  - Economic considerations are often cited as important determinants of health
      seeking behavior. This paper describes a situation in peri-urban Tanzania where
      user fees do not constitute the primary reason why mothers delay seeking prompt
      treatment at a public health facility for their young, febrile children. Mothers
      commonly believe that they are dealing with an ordinary fever and not malaria or
      any other serious illness complicated by fever. Hence, they engage in extended
      home-based treatment. Drawing upon an ethnographic study, this paper illustrates
      how cultural knowledge about disease symptomatology, cultural meanings associated
      with febrile illness, gender relations, and patterns of communication between
      health care providers and mothers significantly influence outcomes for childhood
      febrile illnesses. It is argued that an overemphasis on the correlation between
      user fees and treatment delays with regard to childhood illnesses tends to divert
      attention from other significant cultural factors and existing structural
      constraints that influence the dynamics of health care seeking and health
      outcomes. At a time when calls to implement artemisinine-based combination
      therapy as one of the front-line strategies in Tanzania are increasingly
      frequent, there is a need to pay closer attention to the contextual factors and
      socio-cultural dynamics that influence patterns of treatment-seeking for
      childhood malaria.

PMID- 16403596
TI  - Time in the United States, social support and health behaviors during pregnancy
      among women of Mexican descent.
AB  - Among women of Mexican descent, increased acculturation in the US has been
      associated with poorer health behaviors during pregnancy. This study examined a
      population of low-income women of Mexican descent in an agricultural community to
      determine: whether social support patterns were associated with age at arrival in
      the US; whether social support was associated with pregnancy behaviors; and
      whether increased social support could prevent some of the negative pregnancy
      behaviors that accompany acculturation. Participants were 568 pregnant women
      enrolled in prenatal care in the Salinas Valley, California. Participants were
      predominantly Spanish speaking, born in Mexico, and from farmworker families.
      Information on social networks, social support, age at arrival in the US, and
      pregnancy health behaviors was gathered during interviews conducted during
      pregnancy and immediately after delivery. Poorer health behaviors were observed
      among women who had come to the US at a younger age. Social support during
      pregnancy was lowest among women who had come to the US at an older age. High
      parity, low education, and low income were also associated with low social
      support. Higher social support was associated with better quality of diet,
      increased likelihood of using prenatal vitamins, and decreased likelihood of
      smoking during pregnancy. High social support also appeared to prevent the
      negative impact of life in the US on diet quality. Women with intermediate or low
      levels of social support who had spent their childhoods in the US had
      significantly poorer diet quality than women who had spent their childhoods in
      Mexico. However, among women with high social support, there was no difference in
      diet quality according to country of childhood. Thus, in the case of diet
      quality, increased social support appears to prevent some of the negative
      pregnancy behaviors that accompany time in the US among women of Mexican descent.

PMID- 16403598
TI  - Determining the radial pair-distribution function within intergranular amorphous
      films by numerical nanodiffraction.
AB  - We report on an alternative method to electron nanodiffraction and fluctuation
      microscopy for the determination of the reduced density function G(r) of
      amorphous areas with small cross-sections. This method is based on the numerical
      extraction of diffraction data from the complex-valued exit-face wave function as
      obtained by HRTEM focal series reconstruction or electron holography. Since it is
      thus possible to obtain "diffraction data" from rectangular areas of any aspect
      ratio, this method is particularly suited for intergranular glassy films of only
      1-2 nm width, but lengths of several 100 nm. A critical comparison of this method
      with the already established nanodiffraction and fluctuation microscopy will be
      made.

PMID- 16403597
TI  - The role of education in the uptake of preventative health care: the case of
      cervical screening in Britain.
AB  - This paper reports findings on the relationship between education and the take-up
      of screening for cervical cancer, as an example of preventative health-care
      activity. Theoretically, education can enhance the demand for preventative health
      services by raising awareness of the importance of undertaking regular health
      check-ups and may also improve the ways in which individuals understand
      information regarding periodical tests, communicate with the health practitioner,
      and interpret results. Furthermore, education enhances the inclusion of
      individuals in society, improving self-efficacy and confidence. All these factors
      may increase service uptake. The empirical analysis uses data from the British
      Household Panel Survey (BHPS) and applies techniques for discrete panel data to
      estimate the parameters of the model. Results show that adult learning leading to
      qualifications is statistically associated with an increase in the uptake of
      screening. The marginal effect indicates that participation in courses leading to
      qualifications increases the probability of having a smear test between 4.3 and
      4.4 percentage points. This estimate is strongly robust to time-invariant
      selectivity bias in education and the inclusion of income, class, occupation, and
      parental socio-economic status. These findings enrich existing evidence on the
      socio-economic determinants of screening for cervical cancer and enable policy
      makers to better understand barriers to service uptake.

PMID- 16403599
TI  - Structural analysis of the glycoprotein allergen Hev b 4 from natural rubber
      latex by mass spectrometry.
AB  - The lecithinase homolog (Hev b 4) from Hevea brasiliensis (Q6T4P0_HEVBR) is an
      important natural rubber latex allergen. Hev b 4 is a highly glycosylated protein
      and its carbohydrate moiety has been implicated in the binding of IgE from
      natural rubber latex allergic patients. The cDNA for Hev b 4 has recently been
      cloned and sequenced. Here, we have analyzed the post-translational modifications
      of natural Hev b 4 by liquid chromatography/electrospray ionization-mass
      spectrometry of tryptic peptides. Seven of the eight potential glycosylation
      sites were found to be occupied. One site, however, was only partially
      glycosylated. Asn224 was substituted by complex type N-glycans with fucose and
      xylose, whereas all other sites carried either oligomannose glycans or a mixture
      of oligomannose and complex N-glycans. Glycosylation site Asn308, the most C
      terminal one of the eight sites, was only found in the non-glycosylated form. The
      complex type N-glycans apparently form the molecular basis for the immune
      reaction with patients' sera. A large fraction of Hev b 4 molecules contains two
      or more complex N-glycans and thus a physiological reaction against these
      polyvalent allergens on the basis of the carbohydrate is in theory possible.
      Aside from allowing glycosylation analysis, the mass spectrometric data defined
      the N-terminal cleavage site of Hev b 4. This study once more demonstrates the
      outstanding analytical potential of electrospray ionization-mass spectrometry
      coupled with liquid chromatographic separation.

PMID- 16403601
TI  - Most probable origin of coeliac disease is low immune globulin A in the intestine
      caused by malfunction of Peyer's patches.
AB  - Coeliac disease frequency increases by obscure reasons and affects in some
      Western countries as much as 1% of the populations. The second one of monozygotic
      twins does not develop the disease in 100% but only in 20-50%. To unravel these
      mysteries, literature was searched to determine the disease background and find
      suggestions for research and prevention. The causal antigen of coeliac disease is
      gluten of wheat that is neutralised in the intestine by secretory immune globulin
      A (sIgA). SIgA is secreted by the secondary (lymphoid) immune system that
      develops in a newborn infant after the primary (central) immune organs thymus and
      bone marrow have been primed with antigens of the intestine. Predisposed infants
      are sensitive for development of coeliac disease during the time without sIgA
      secretion into the intestine. The risk of the disease diminishes when sIgA cycles
      of gluten neutralisation develop. Peyer's patches (PP) of the secondary immune
      system play a central role in the cycles and possibly do not function well in the
      case of coeliac disease. Coeliac disease in predisposed infants may be prevented
      by delay of bread consumption till the time of normal sIgA secretion and by
      application of a challenge period with gluten (see Discussion). It is concluded
      that sIgA secretion into body cavities and malfunction of immune cells in PP
      should be included in the future research of coeliac disease as well as in more
      allergic diseases (type 1 diabetes, Crohn disease, asthma, hay fever).

PMID- 16403600
TI  - Dictyostelium discoideum to human cells: pharmacogenetic studies demonstrate a
      role for sphingolipids in chemoresistance.
AB  - Resistance to chemotherapy is a major obstacle for the treatment of cancer and a
      subject of extensive research. Numerous mechanisms of drug resistance have been
      proposed, and they differ for different drugs. Nevertheless, it is clear that our
      understanding of this important problem is still incomplete, and that new targets
      for modulating therapy still await discovery. The attractive biology and the
      availability of powerful molecular techniques have made the cellular slime mold
      Dictyostelium discoideum, a powerful non-mammalian model for drug target
      discovery, and the problem of drug resistance. To understand the molecular basis
      of chemoresistance to the widely used drug cisplatin, both genetic and
      pharmacological approaches have been applied to this versatile experimental
      system. These studies have resulted in the identification of novel molecular
      pathways which can be used to increase the efficacy of cisplatin, and brought
      attention to the role of sphingolipids in mediating the cellular response to
      chemotherapeutic drugs. In the following review, we will describe the history and
      utility of D. discoideum in pharmacogenetics, and discuss recent studies which
      focus attention on the role of sphingolipids in chemotherapy and chemoresistance.

PMID- 16403602
TI  - DNA based customized nutraceutical "gene therapy" utilizing a genoscore: a
      hypothesized paradigm shift of a novel approach to the diagnosis, stratification,
      prognosis and treatment of inflammatory processes in the human.
AB  - We hypothesize that using a multi-variant nutrigenomic index for the purposes of
      customizing or adjusting the formulation of nutritional supplements will result
      in an improved and novel approach to the diagnosis, stratification, prognosis,
      and treatment of inflammatory processes in the human. This multi-variant genetic
      index, or Genoscore, is derived by analyzing genotype and/or phenotype through
      measuring multiple genetic mutations of single nucleotide polymorphisms, gene
      expression, or other forms of genetic and phenotypic measurements. We also
      propose that manipulation of neurochemical reward circuitry in the mesolimbic
      brain region providing dopamine release at the nucleus accumbens (NAc), will have
      both pain and stress relief benefists, which are a cornerstone to the human
      inflammatory process. This hypothesis, applies to all genes currently discovered
      or which will be discovered and any nutritional or dietary supplement ingredient
      currently available or which will become available. For example, if a DNA test
      was measuring two genes through single nucleotide polymorphisms (Gene A and Gene
      B), the index scores (Genoscore) that would be reported to the clinician and
      patient would be based upon the number of mutations. An index score of 0 would
      mean no mutation. An index score of 1 may mean a mutation in Gene A. An Index
      Score of 2 may mean a mutation in Gene B. An Index Score of 3 may mean a mutation
      in Gene A and Gene B, resulting in a simple report, easily understandable to both
      the clinician and patient that provides insights into disease diagnosis,
      stratification, prognosis, as well as the metabolism, efficacy and/or toxicity
      associated with specific vitamins, minerals, herbal supplements, homeopathic
      ingredients and other ingredients in the nutritional and/or dietary supplement
      regimen. Furthermore, we have provided support that evidence shows the importance
      of the dopaminergic connection as an anti-pain and anti-stress molecule, working
      at the mesocorticolimbic region of the brain, specifically at the NAc.
      Additionally, we have provided support that clinical evidence demonstrates the
      effectiveness and safety of natural substances for joint health, such as
      glucosamine sulfate , chondroitin sulfate, and Ganoderma lucidum.

PMID- 16403604
TI  - Rheumatoid arthritis induced-fatty liver theory: one reason for global increase
      in prevalence of diabetes.

PMID- 16403603
TI  - An avian influenza vaccine for humans targeting the polymerase B2 protein inside
      the capsid instead of hemagglutinin or neuramidase on the virus surface.
AB  - Vaccines for avian influenza typically are aimed at hemagglutinin or neuramidase
      on the outside of the virus capsid. A major problem with such an approach is that
      the genes coding for these proteins have a very rapid mutation rate, forcing
      commercial producers to wait for mutations to occur before developing effective
      new versions of standard vaccines. However, a recent study has revealed that the
      1918 flu virus, like the H5N1 avian flu virus, has an E627K mutation in its
      polymerase B2 component, which is located inside the virus capsid. Other research
      has indicated that this mutation strongly influences the virulence of H5N1. It
      seems reasonable to believe that the constancy, over more than 80 years, of the
      E627K mutation could be exploited to begin developing a vaccine now, rather than
      waiting for new mutations. Consequently, a publicly available database at the
      National Center for Biotechnology Information (NCBI) website, and the SYFPEITHI
      online computer algorithm, were used to generate a hypothesis about a peptide
      based vaccine targeted at the E627K mutation in PB2 of the avian influenza virus.
      It was found that the peptide sequence, DTVQIIKLL, present in the PB2 protein of
      the H5N1 virus, would be expected to bind to HLA-A26 restricted immune system
      cell surface receptors. Hence, the bound peptide might be capable of stimulating
      protection from cytotoxic T lymphocytes. Should the present hypothesis be
      confirmed in laboratory studies, and an effective vaccine developed for
      individuals expressing the HLA-A26 receptor; further research would be indicated.
      This research would be aimed at determining whether molecular modifications to
      the DTVQIIKLL peptide could make it effective with other members of the HLA-A1
      supertype to which HLA-A26 belongs. In addition to allowing vaccine development
      to begin now, this peptide-based approach would have the advantage of avoiding
      the use of dangerous, live, avian influenza virus during mass production.

PMID- 16403605
TI  - Antioxidant and heme oxygenase-1 (HO-1)-induced effects of selected Taiwanese
      plants.
AB  - Recent studies have shown biological effects of heme oxygenase-1 (HO-1) induction
      and antioxidation in cardiovascular disorders. The ethanol extracts of leaves of
      12 selected indigenous Taiwanese plants were investigated for their antioxidant
      activities, evaluated using assays of 1,1-diphenyl-2-picrylhydrazyl (DPPH),
      hydroxyl, and superoxide radicals scavenging and reducing power activities as
      well as the induction of heme oxygenase-1 (HO-1). Acer albopurpurascens,
      Cinnamomum kanehirai, Diospyros discolor, Excoecaria kawakamii, Koelreuteria
      henryi, and Syzygium formosanum showed better DPPH-scavenging activities than the
      other plants. IC(50) values ranged from 1.7 to 8.7 microg/mL. Excepting Millettia
      pulchra var. microphylla and Pittosporum moluccanum, the extracts displayed
      hydroxyl-scavenging activities (IC(50) of 0.16-0.67 microg/mL). A.
      albopurpurascens, D. discolor, K. henryi, and S. formosanum also showed good
      superoxide anion radical scavenging activities and IC(50) values ranged from 12.9
      to 28.5 microg/mL. D. discolor, K. henryi, and S. formosanum showed potent
      reducing power and M. pulchra var. microphylla and S. formosanum exhibited potent
      HO-1 induced activity. These active plant extracts also contained abundant
      phenolic constituents. The present results provide candidates to isolate the
      active constituents and develop natural antioxidants.

PMID- 16403606
TI  - Hepatocyte growth factor-regulated genes in differentiated RAW 264.7 osteoclast
      and undifferentiated cells.
AB  - Hepatocyte Growth Factor (HGF) and its protooncogene receptor c-Met regulate
      osteoclast function by activating pp60(c-Src) kinase and alpha(v)beta3 integrin.
      HGF causes transcription yet in osteoclast cells, this gene regulation is
      currently unknown. To begin characterization of HGF-regulated gene expression in
      osteoclast cells, we used a well characterized model of osteoclast cells. Using
      microarray, relative RT-PCR, and Western blot analyses, we have identified and
      confirmed differentially expressed genes in RAW 264.7 osteoclast cells in
      response to HGF. HGF regulation of transcription of these genes was concordant
      with microarray results. We report that HGF downregulates transcription factors,
      Distal-less 5 (Dlx-5), Distal-less 6 (Dlx-6) and Aristaless 4 (Alx-4), in RAW
      264.7 osteoclast cells but has an inverse effect in undifferentiated RAW 264.7
      cells.

PMID- 16403607
TI  - Evidence for a novel mitochondria-to-nucleus signalling pathway in respiring
      cells lacking i-AAA protease and the ABC-transporter Mdl1.
AB  - Peptides generated upon degradation of mitochondrial proteins by various ATP
      dependent proteases are continuously released from mitochondria raising the
      intriguing possibility of a role of these peptides in interorganellar
      communication. Here, we have determined genome-wide transcript profiles of mutant
      yeast cells defective in mitochondrial peptide export. Deletion of YME1, coding
      for the i-AAA protease in the inner membrane, abolished peptide generation in the
      intermembrane space and led to the induction of nuclear genes with functions in
      mitochondrial gene expression and the biogenesis of the respiratory chain. On the
      other hand, deletion of MDL1, coding for an ABC-transporter involved in peptide
      export from the matrix space, only had minor effects on nuclear gene expression.
      It strengthened, however, the response in Deltayme1 cells suggesting a link
      between mitochondrial peptide export and nuclear gene expression. The response in
      Yme1-deficient cells depended on respiratory growth and was not observed in
      fermenting yeast cells. Inhibition of the F1FO-ATP synthase induced Deltayme1
      responsive genes whereas inhibition of the respiratory chain or dissipation of
      the mitochondrial membrane potential resulted in their repression. These findings
      suggest the existence of a novel mitochondria-to-nucleus signalling pathway in
      respiring cells which allows the re-adjustment of the biogenesis of the
      respiratory chain in response to an altered activity of the F1FO-ATP synthase.

PMID- 16403608
TI  - Chicken LRH-1 gene is transcribed from multiple promoters in steroidogenic
      organs.
AB  - Liver receptor homolog-1 (LRH-1) is a homolog of FTZ-F1, a transcription factor
      of the fruit fly, and belongs to the orphan nuclear receptor family. LRH-1 is
      expressed in organs derived from the endoderm, including intestine, liver and
      exocrine pancreas and plays a predominant role in development, bile-acid
      homeostasis, and reverse cholesterol transport. Recent research has revealed that
      mammalian LRH-1 is also expressed in the steroidogenic organs and has suggested
      that LRH-1 shares a role in steroidogenesis with steroidogenic factor-1 (SF-1),
      which is a paralog of LRH-1. In this study, we determined transcription
      initiation sites of chicken LRH-1 and showed that LRH-1 is expressed as several
      splicing variants in chicken steroidogenic organs. From three steroidogenic
      organs, the adrenal glands, ovaries, and testes, several cDNA fragments including
      different lengths and sequences were amplified by 5'-RACE and these were mainly
      classified into five types. Using these sequences, chicken genomic database was
      searched and four types of first exons were identified in chromosome 8. However,
      the database sequence of these regions included several gaps. So we cloned gap
      regions by PCR cloning from chicken genomic DNA and found the other type of first
      exons in the gaps. Moreover, RT-PCR showed the expression of LRH-1 in chicken
      steroidogenic organs as many splicing variants. We concluded that the chicken LRH
      1 gene is transcribed from at least five different transcription initiation sites
      and alternative splicing produces several types of mRNA in steroidogenic organs.

PMID- 16403609
TI  - A model of real time monitoring of the cochlear function during an induced local
      ischemia.
AB  - The aim of this study was to investigate the utility of distortion product
      otoacoustic emissions (DPOAEs) in intraoperative monitoring (IM) of cochlear
      ischemic episodes in animals during internal auditory artery (IAA) compression.
      The IAA was exposed using the posterior fossa approach and then compressed for 3
      and 5 min intervals to effect ischemia. DPOAE amplitudes and phases were measured
      at 4, 8, and 12 kHz geometric mean frequency (GMF). In each monitored ear, laser
      Doppler cochlear blood flow (CBF) was measured. All IAA compressions resulted in
      rapid decrease of DPOAE amplitude and CBF, with simultaneous DPOAE phase
      increase. DPOAE phase changes were found to increase consistently within several
      seconds of IAA compression, while corresponding DPOAE amplitudes changed more
      slowly, with up to 30-40 s delays. Following IAA release, DPOAEs at 12 kHz GMF
      were characterized by longer delays in returning to baseline than those measured
      at lower frequencies. In some cases, CBF did not return to baseline. In this
      animal model, DPOAEs were found to be sensitive measures of cochlear function
      during transient cochlear ischemic episodes, suggesting the utility of DPOAE
      monitoring of auditory function during surgery of cerebello-pontine angle tumors.

PMID- 16403610
TI  - Auditory evoked-potential correlates of decrement detection.
AB  - Decrement detection is a commonly used psychophysical technique in which a
      subject is required to detect partially filled gaps in an ongoing sound. The
      paradigm provides information regarding both temporal resolution and intensity
      discrimination. The purpose of this project was to determine if an evoked
      potential paradigm using decrements in an ongoing noise approximates
      psychophysical data. If so, the evoked-response paradigm would be useful in
      estimating decrement detection in laboratory animals, where training time for a
      psychophysical model of decrement detection might prove prohibitive. In this
      study, Mongolian gerbils aged 3-10 months were used as subjects. The stimulus was
      a broadband noise (low-pass filtered at 5 or 30 kHz, overall level of 70 dB SPL),
      interrupted for durations of 2-32 ms. Within each off period, a second,
      identically filtered noise at levels of 0-70 dB SPL was presented. In a manner
      qualitatively similar to previous human and animal psychophysical studies, the
      ABR threshold decreased as the duration of the decrement was increased. Latency
      and amplitudes changed as a function of decrement duration when the decrement
      depth was held constant, but minimal change as a function of decrement depth
      occurred when the decrement duration was held constant. The results suggest that
      ABR paradigm for decrement detection is a qualitative alternative to
      psychophysical techniques, but that amplitude and latency data may not provide
      more information on temporal and intensity coding than ABR measures of gap
      detection.

PMID- 16403611
TI  - Psychophysical measures in patients fitted with Contour and straight Nucleus
      electrode arrays.
AB  - The objective of this study was to compare the psychophysical performance of
      patients using the Nucleus Contour electrode array with that of patients using
      the straight banded-electrode array. In particular, we wished to consider how
      psychophysical parameters would differ for an electrode array positioned closer
      to the modiolus, and how this might influence both patient benefits and the
      design of speech processing strategies. Nine subjects participated in the study:
      four used the Nucleus straight array and five used the Nucleus Contour electrode
      array. Radiographic analyses found that the Contour array lay closer to the
      modiolus, was more deeply inserted and spanned a larger fractional length of the
      basilar membrane than the straight banded-electrode array. The results were
      analysed in terms of array type and of the position of the individual electrode
      band, both distance from the modiolus and longitudinal placement. Mean threshold
      was lower for the Contour array but maximum comfortable level was similar.
      Whereas threshold varied significantly with distance of electrode band from the
      modiolus, maximum comfortable level did not. Pitch varied fairly regularly with
      longitudinal position of the stimulated electrode, with the exception of one
      Contour subject. The forward masking profiles, using moderately loud maskers,
      were narrower for the Contour array, indicative of more localized neural
      excitation.

PMID- 16403612
TI  - Challenges in biocatalysis for enzyme-based biofuel cells.
AB  - Enzyme-based biofuel cells are attracting attention rapidly partially due to the
      promising advances reported recently. However, there are issues to be addressed
      before biofuel cells become competitive in practical applications. Two critical
      issues are short lifetime and poor power density, both of which are related to
      enzyme stability, electron transfer rate, and enzyme loading. Recent progress in
      nanobiocatalysis opens the possibility to improve in these aspects. Many nano
      structured materials, such as mesoporous media, nanoparticles, nanofibers, and
      nanotubes, have been demonstrated as efficient hosts of enzyme immobilization. It
      is evident that, when nanostructure of conductive materials are used, the large
      surface area of these nanomaterials can increase the enzyme loading and
      facilitate reaction kinetics, and thus improving the power density of biofuel
      cells. In addition, research efforts have also been made to improve the activity
      and stability of immobilized enzymes by using nanostructures. It appears to be
      reasonable to us to expect that progress in nanostuctured biocatalysts will play
      a critical role in overcoming the major obstacles in the development of powerful
      biofuel cells.

PMID- 16403613
TI  - Frequency tuning in animal locomotion.
AB  - In locomotion that involves repetitive motion of propulsive structures (arms,
      legs, fins, wings) there are resonant frequencies f(*) at which the energy
      consumption is a minimum. As animals need to change their speed, they can
      maintain this energy minimum by tuning their body resonances. We discuss the
      physical principles of frequency tuning, and how it relates to forces, damping,
      and oscillation amplitude. The resonant frequency of pendulum-type oscillators
      (e.g. swinging arms and legs) may be changed by varying the mass moment of
      inertia, or the vertical acceleration of the pendulum pivot. The frequency of
      elastic vibrations (e.g. the bell of a jellyfish) can be tuned with a non-linear
      modulus of elasticity: soft for low deflection amplitudes (low resonant
      frequency), and stiff for large displacements (high resonant frequency). Tuning
      of elastic oscillations can also be achieved by changing the effective length or
      cross-sectional area of the elastic members, or by allowing springs in parallel
      or in series to become active. We propose that swimming and flying animals
      generate oscillating propulsive forces from precisely placed shed vortices and
      that these tuned motions can only occur when vortex shedding and the simple
      harmonic motion of the elastic elements of the propulsive structures are in
      resonance.

PMID- 16403614
TI  - Clinical differences in the Global Initiative for Chronic Obstructive Lung
      Disease Stage 0.
AB  - This study was to examine the clinical differences between Stage 0 and normal
      subjects, using low-dose chest computed tomography (CT) and pulmonary function
      tests. Enrolled subjects performed as a health check for lung cancer screening
      including low-dose CT and pulmonary function tests. Subjects were divided into
      Stage 0, chronic obstructive pulmonary disease according to pulmonary function
      tests, and normal subjects. The severity of emphysema (visual score) was
      calculated on three low-dose CT slices. Low-dose CT and pulmonary function tests
      were performed in 1359 men and 888 women. The numbers and percentages of men and
      women smokers were 1076 (79.2%), and 107 (12.0%), respectively. A total of 722
      individuals had one or more respiratory symptoms, such as cough (69.8%), sputum
      (75.8%), or shortness of breathing (0.83%). Of the 722 subjects, 71 (9.8%)
      individuals satisfied the criteria of chronic respiratory symptoms. Among the
      normal subjects, smoking caused differences in airflow limitation as a result of
      pulmonary function tests. The proportion of smokers and the visual score were
      significantly higher in Stage 0 than those in the normal subjects. The
      percentages of the maximal mid-expiratory flow (%MMF) and of the peak expiratory
      flow rate were significantly lower in Stage 0 than in the normal subjects. %MMF
      and the proportion of visual score were significantly lower in the smoking Stage
      0 than in the nonsmoking Stage 0 subjects. Smoking would indicate early signs of
      emphysematous change between Stage 0 and normal subjects in comparison of
      pulmonary function tests and visual score of low-dose CT.

PMID- 16403615
TI  - High-frequency oscillatory ventilation in an infant with cystic fibrosis and
      bronchiolitis.
AB  - Infants with cystic fibrosis (CF) may develop severe respiratory compromise
      related to viral lower respiratory tract infections due to impaired mucous
      clearance and plugging of small airways. Consequently air trapping may lead to
      lung hyperinflation, impaired gas exchange, and respiratory failure. We describe
      the case of an infant with newly diagnosed CF who developed severe hypercarbic
      respiratory failure in the setting of viral bronchiolitis successfully treated
      with high-frequency oscillatory ventilation (HFOV).

PMID- 16403616
TI  - Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma: a
      multi-center, double-blind, randomized, and placebo-controlled study in Taiwan.
AB  - Sublingual immunotherapy (SLIT) has been recommended as a viable alternative to
      subcutaneous injection therapy in the treatment of airway allergies, though more
      data is needed from well-controlled studies for documenting its efficacy in
      different ethnic populations. Ninety-seven children (age range 6-12 years), mild
      to-moderate asthma with a single sensitization to mite allergen, were enrolled
      from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with
      standardized mite extracts, which contain Dermatophagoides pteronyssinus (D.p.)
      and Dermatophagoides farinae (D.f.). Patients were double blinded and randomly
      assigned to either a SLIT or placebo group. Following 24 weeks of study period,
      symptom and medication scores, lung function tests, skin prick tests, total serum
      IgE, and specific IgE to D.p. and D.f. were recorded. The results showed that
      there was statistically significant difference between these two groups in the
      analysis of daily (P=0.011), nighttime (P=0.028), and daytime (P=0.009) asthmatic
      scores after 24 weeks of treatment. Patients receiving SLIT improved their forced
      vital capacity (FVC), forced expiratory volume in 1s (FEV1), and peak expiratory
      flow (PEF) as compared to baseline (P=0.042, P=0.048, and P=0.001, respectively).
      No differences were found in skin prick test, total serum IgE and specific IgE to
      D.p. and D.f. Tolerance with high-dose SLIT was good with few minor adverse
      events reported. Our results indicated that a 24-week SLIT is of clinical benefit
      to mite-sensitive asthmatic children in Taiwan.

PMID- 16403617
TI  - Asthma and allergy in alpha-1 antitrypsin deficiency.
AB  - This study was designed to determine the prevalence of asthma and atopy, in a
      large group of subjects with alpha-1 antitrypsin deficiency (AATD) participating
      in the Alpha-1 Foundation Research Registry. A survey was mailed to all Registry
      participants (N=2418) and results were collated by AATD phenotype. Participants
      with PiZZ deficiency were compared to PiMZ and other phenotypes by nonparametric
      statistics. Responses were collected from 757 participants (31%). Overall 44.6%
      (N=338) reported MD diagnosed asthma. Wheezing was reported in 76% with
      respiratory infections, activity and exposure to dusts, fumes, and allergens as
      common triggers. Across the three groups reported asthma with a history of
      allergies was reported from 20% to 25%. Wheezing symptoms were significantly less
      common in the PiMZ group compared with other groups. Of those reporting asthma,
      83% of the PiZZ group (n=192) also reported another chronic obstructive pulmonary
      disease (COPD) diagnosis compared to 48% of the PiMZ group (n=24). Asthma as the
      only reported diagnosis was three times more prevalent in the PiMZ group compared
      with the PiZZ group. Although asthma diagnosis is imprecise in the presence of
      COPD, the high prevalence of wheezing to allergen and irritant exposures with
      symptoms of atopy suggests that asthma is common in AATD but usually associated
      with COPD. Those with AATD who are susceptible to asthma require allergy
      evaluation and aggressive anti-inflammatory strategies as part of their
      management.

PMID- 16403618
TI  - Demobilisation of critical contaminants in four typical waste-to-energy ashes by
      carbonation.
AB  - Two bottom ashes, one air pollution control (APC) residue and one fly ash from
      three different Swedish municipal solid waste incineration (MSWI) plants were
      characterised regarding the leaching of environmentally relevant components.
      Characterisation was performed using a diffusion tank leaching test. The impact
      of carbonation on the release of eight critical components, i.e., Cl(-), Cr, Cu,
      Mo, Pb, Sb, Se, SO(4)(2-) and Zn, was assessed at a lab-scale and showed
      carbonation to have a more pronounced demobilising effect on critical components
      in bottom ashes than in APC residue and fly ash. From grate type incinerator
      bottom ash, the release of Cr decreased by 97%, by 63% for Cu and by 45% for Sb.
      In the investigated APC residue, the releases of Cr, Se and Pb were defined as
      critical, although they either remained unaffected or increased after
      carbonation. Cl(-) and SO(4)(2-) remained mobile after carbonation in all
      investigated residues.

PMID- 16403619
TI  - Changes in carbon and nitrogen pool during in-situ aeration of old landfills
      under varying conditions.
AB  - Emissions from old landfills via leachate and the gas phase are influenced by
      state and stability of the organic matter in the solid waste and by environmental
      conditions within the landfill. Remediation of landfills by means of in-situ
      aeration is one possibility to reduce these emissions. By establishing aerobic
      conditions, biological processes in the landfill are accelerated. To investigate
      the effects of this remediation technology, lab-scale experiments with column
      tests have been carried out. The main goal of the present work is to characterize
      the changes of the carbon and nitrogen compounds in the aerated solid waste, the
      leachate and the gas phase under varying conditions. The results demonstrate a
      clear reduction of emissions and a stabilization of the organic matter.
      Furthermore, it is shown that both the intensity of aeration and the amount of
      water affect biological processes to a certain extent. Even when columns were
      operated under anaerobic conditions after a long running period of aeration, the
      emissions remained low.

PMID- 16403620
TI  - Reduced sulfur compounds in gas from construction and demolition debris
      landfills.
AB  - The biological conversion of sulfate from disposed gypsum drywall to hydrogen
      sulfide (H(2)S) in the anaerobic environment of a landfill results in odor
      problems and possible health concerns at many disposal facilities. To examine the
      extent and magnitude of such emissions, landfill gas samples from wells, soil
      vapor samples from the interface of the waste and cover soil, and ambient air
      samples, were collected from 10 construction and demolition (C&D) debris
      landfills in Florida and analyzed for H(2)S and other reduced sulfur compounds
      (RSC). H(2)S was detected in the well gas and soil vapor at all 10 sites. The
      concentrations in the ambient air above the surface of the landfill were much
      lower than those observed in the soil vapor, and no direct correlation was
      observed between the two sampling locations. Methyl mercaptan and carbonyl
      sulfide were the most frequently observed other RSC, though they occurred at
      smaller concentrations than H(2)S. This research confirmed the presence of H(2)S
      at C&D debris landfills. High concentrations of H(2)S may be a concern for
      employees working on the landfill site. These results indicate that workers
      should use proper personal protection at C&D debris landfills when involved in
      excavation, landfill gas collection, or confined spaces. The results indicate
      that H(2)S is sufficiently diluted in the atmosphere to not commonly pose acute
      health impacts for these landfill workers in normal working conditions. H(2)S
      concentrations were extremely variable with measurements occurring over a very
      large range (from less than 3 ppbv to 12,000 ppmv in the soil vapor and from less
      than 3 ppbv to 50 ppmv in ambient air). Possible reasons for the large intra- and
      inter-site variability observed include waste and soil heterogeneities, impact of
      weather conditions, and different site management practices.

PMID- 16403621
TI  - Thermal conversion of rice husks and sawdust to liquid fuel.
AB  - The paper focuses on studying the conversion of rice husks and sawdust into
      liquid fuel. Rice husks, sawdust and their mixture are pyrolyzed at temperatures
      between 420 and 540 degrees C, and the main product of liquid fuel is obtained.
      The experimental result shows that the yield of liquid fuel depends on various
      factors such as feedstock and temperature. The maximum yields for rice husks,
      sawdust and their mixture are 56%, 61% and 60% at 465, 490 and 475 degrees C,
      respectively. Analyses with GC-MS and other apparatus show that the liquid fuel
      is a complicated compound with low caloric value and can be directly used as a
      fuel oil for combustion in a boiler or a furnace without any upgrading.
      Alternatively, the fuel can be refined to be used by vehicles.

PMID- 16403622
TI  - High positive sentinel node identification rate by EORTC melanoma group protocol.
      Prognostic indicators of metastatic patterns after sentinel node biopsy in
      melanoma.
AB  - Methods to work-up sentinel nodes (SN) vary considerably between institutes. This
      single institution study evaluated the positive SN-identification rate of the
      EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the
      SN status regarding disease-free survival (DFS) and overall survival (OS) and
      evaluated the locoregional control after the SN procedure. Multivariate and
      univariate analyses using Cox's proportional hazard regression model was employed
      to assess the prognostic value of covariates regarding DFS and OS. The positive
      SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the
      false-negative rate was 9.4%. Breslow thickness and ulceration of the primary
      correlated with SN status. SN status, ulceration and site of the primary tumour
      correlated with DFS. SN status and ulceration of the primary correlated with OS.
      The in-transit metastasis rate correlated with SN-positivity, Breslow thickness
      and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive
      patients. Transhilar bivalving of the SN with step sections from the central
      planes is simple and had a high SN-positive detection rate of about 30%. The SN
      status is the most important predictive value for DFS and OS. In-transit
      metastasis rates correlated with SN-positivity, Breslow thickness and ulceration
      of the primary.

PMID- 16403623
TI  - Changes in multiple myeloma epidemiology in the last thirty years: a single
      centre experience.
AB  - In this study we have evaluated 772 multiple myeloma (MM) patients for clinical
      presentation, response to treatment, relapse modality, and survival in the last
      30 years. Patients were divided, according to the date of diagnosis in group I or
      group II (before and after 1994, respectively) and therapy (high or conventional
      dose). Bone pain and early deaths were statistically reduced in group II, whereas
      MM that evolved from monoclonal gammopathy of undetermined significance (MGUS)
      had increased. The efficacy of high dose therapy (HDT) over conventional dose
      therapy (CDT) was confirmed through analysis of response rate, progression free,
      and overall survival. Relapse modality was similar after HDT or CDT. Among older
      patients, those diagnosed after 1994 lived longer than those diagnosed before
      1994. In the last 30 years, the clinical presentation of multiple myeloma
      remained substantially unchanged. The new therapeutic approaches, chemotherapy
      and supportive therapy, allowed better control of the disease with an improvement
      of survival.

PMID- 16403624
TI  - Structure-activity relationship studies on niphimycin, a guanidylpolyol macrolide
      antibiotic. Part 1: The role of the N-methyl-N''-alkylguanidinium moiety.
AB  - Several N-methyl-N''-alkylguanidinium derivatives were synthesized and used as
      simplified analogues of niphimycin (NM), a guanidylpolyol macrolide, in structure
      activity relationship studies. The C16-alkylated derivative exerted fungicidal
      activity by directly damaging the fungal plasma membrane and inducing oxidative
      stress in a manner similar to niphimycin. These results indicate that the N
      methyl-N''-alkylguanidinium moiety is required for antifungal activity by NM.

PMID- 16403625
TI  - Chemo-enzymatic synthesis of allyl penta-N-acetyl-chitopentaose.
AB  - Cell density cultivation of recombinant Escherichia coli strains harboring the
      nodC gene (encoding chitooligosaccharide synthase) from Azorhizobium caulinodans
      has been previously described as a practical method for the preparation of gram
      scale quantities of penta-N-acetyl-chitopentaose. We have now extended this
      method to the production of allylated derivative of penta-N-acetyl-chitopentaose
      by using allyl 2-acetamido-2-deoxy-beta-d-glucopyranoside (2) as the initial
      acceptor for the synthesis of target pentaoside in vivo.

PMID- 16403627
TI  - Gallium(III) complexes of methyl pyropheophorbide-a as synthetic models for
      investigation of diastereomerically controlled axial ligation towards
      chlorophylls.
AB  - Gallium(III) chlorins possessing a series of axial ligands were synthesized as
      model compounds of natural chlorophylls. A pair of diastereomers arising from the
      fifth axial coordination onto the asymmetric chlorin pi-macrocycle could be
      discriminated in a solution by both (1)H- and (13)C NMR spectroscopies.

PMID- 16403626
TI  - Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of
      protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological
      evaluation.
AB  - A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been
      prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent
      inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range
      against Akt1. Compound 2q shows excellent selectivity against distinct families
      of kinases such as tyrosine kinases and CAMK, and displays poor to modest
      selectivity against closely related kinases in the AGC and CMGC families. The
      cellular activities including inhibition of cell growth and phosphorylation of
      downstream target GSK3 are also described. The X-ray structure of compound 2q
      complexed with PKA in the ATP binding site was determined.

PMID- 16403628
TI  - Synthesis and screening of bicyclic carbohydrate-based compounds: a novel type of
      antivirals.
AB  - A small library of bicyclic carbohydrate derivatives was synthesized and
      screened. A strong and selective activity against cytomegalovirus was found.
      Structure-activity relationship for this new type of antivirals is discussed.

PMID- 16403629
TI  - Aryl O- and S-galactosides and lactosides as specific inhibitors of human
      galectins-1 and -3: role of electrostatic potential at O-3.
AB  - Phase transfer catalyzed reaction was used for the high yielding synthesis of
      aryl 1-thio-beta-d-galacto- and lacto-pyranosides carrying a panel of
      substituents on the phenyl groups. Best galectin-1 inhibitors were simple p
      nitrophenyl thiogalactoside 5a for the monosaccharide and o-nitrophenyl
      thiolactoside 6f or napthylsulfonyl lactoside 8c, both being 20 times better
      relative to natural ligands. Relative inhibitory properties as low as 2500 and 40
      microM were observed, respectively. The electronic effects of the lactoside
      aglycons directly influenced the electrostatic potential at O-3, which was
      associated with the inhibitory potencies against galectin-1.

PMID- 16403630
TI  - Synthesis and evaluation of novel 8-oxo-8H-cyclopenta[a]acenaphthylene-7
      carbonitriles as long-wavelength fluorescent markers for hypoxic cells in solid
      tumor.
AB  - Novel bioreductive and long-wavelength fluorescent markers for hypoxic cells in
      solid tumor, 9-isocyano-8H-acenaphtho[l,2-b]pyrrol-8-one with the side chain of 2
      nitroimidazole, were designed, synthesized, and evaluated in V79 379A Chinese
      hamster cells in vitro. Compounds A(2) and A(4) showed good hypoxic-oxic
      fluorescence differential in vitro (V79 cells) by using fluorescence scan ascent.

PMID- 16403631
TI  - Brucellar breast abscess.
AB  - Brucellosis is an endemic disease seen in many countries. It may affect different
      organ systems. Brucellar breast abscess is a rare entity. We report the
      radiological findings of breast abscess due to brucella. A 63-year-old female was
      investigated with mammography, ultrasonography, magnetic resonance imaging (MRI),
      and magnetic resonance spectroscopy (MRS). A mass measuring 25 x 20 x 15 mm was
      detected in the left breast on mammography and ultrasonography. The mass was
      homogenously hyperintense on T1- and T2-weighted MRI images. On contrast-enhanced
      T1-weighted images, peripheral capsular enhancement was found. MR spectroscopic
      analysis of the mass revealed elevated lipid and acetate peaks. The diagnosis was
      provided by fine needle aspiration biopsy and specimen culture. The lesion had
      diminished in size after 12 months' treatment with combined tetracycline and
      rifampicine.

PMID- 16403632
TI  - Relationship between IL-10 and tumor markers in breast cancer patients.
AB  - Tumor markers are expressed due to molecular alterations of the tumor cells, and
      we can relate them to the immune system to find new associations to improve
      prognosis. IL-10 inhibits the generation of immune responses at the tumor site.
      To determine IL-10 expression in the tumor microenvironment and to associate it
      with certain tumor markers, 27 breast cancer patients were monitored by
      immunohistochemistry. The results showed that 23 breast cancer samples exhibited
      a strong expression of IL-10. IL-10 was associated with some poor prognosis tumor
      makers. A direct association between IL-10, Bcl-2, and Bax was detected. The
      relationship between IL-10 and Bax was statistically significant (P=0.001). An
      inverse association of IL-10 with p53 was observed. IL-10 reflects a suppressive
      tumor microenvironment, and its relationship with apoptosis markers can suggest
      an increase in the aggressiveness of the tumor even if it still is at an early
      stage.

PMID- 16403633
TI  - Amyloid in neurosurgical and neurological practice.
AB  - The amyloidoses are a diverse group of diseases characterized by the deposition
      of specific proteins with distinct affinity to the dye Congo red, collectively
      called amyloid. The amyloidogenic proteins have acquired an abnormal, highly
      ordered, beta-pleated sheet configuration with a propensity to self-aggregate.
      The amyloid may be distributed in different organs with a remarkable diversity.
      Two broad categories of amyloidoses are recognised: The systemic (consisting of
      the primary or light chain form, the secondary or reactive form and the familial
      or hereditary form) and the localised that target specific organs. A tropism of
      amyloid proteins to the neural tissue produces certain patterns of central
      nervous system diseases: cerebral amyloid angiopathy, a substrate of spontaneous
      intracerebral haemorrhage; mature neuritic plaques found in Alzheimer disease and
      a subset of prion diseases; a topographically restricted accumulation of
      extracellular proteins giving rise to tumour-mimicking masses, the amyloidomas;
      and finally, spinal extradural amyloid collections that occasionally are found in
      the context of rheumatoid arthritis. In this review article we present original
      illustrative cases of amyloid diseases of the central nervous system that may be
      encountered in neurosurgical and neurological practice. Molecular aspects and
      clinical management problems are discussed.

PMID- 16403634
TI  - Novel modes of splicing repression by PTB.
AB  - Polypyrimidine-tract-binding protein (PTB) is a repressive regulator of
      alternative splicing. Models for PTB activity have ranged from simple binding
      competition with splicing factor U2AF(65) at regulated polypyrimidine tracts to
      looping out of repressed exons by binding of PTB to flanking sites. Structural
      analysis of PTB bound to RNA suggests how PTB monomers can induce loops, but two
      recent publications indicate that repression by PTB involves more than just
      binding to RNA.

PMID- 16403635
TI  - Cellular co-factors of HIV-1 integration.
AB  - To achieve productive infection, the reverse transcribed cDNA of human
      immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome. The
      main protein responsible for this reaction is the viral integrase. However,
      studies indicate that the virus is assisted by cellular proteins, or co-factors,
      to achieve integration into the infected cell. The barrier-to-autointegration
      factor (BAF) might prevent autointegration. Its ability to bridge DNA and the
      finding that the nuclear lamina-associated polypeptide-2alpha interacts with BAF
      suggest a role in nuclear structure organization. Integrase interactor 1 was
      found to directly interact with HIV-1 integrase and to activate its DNA-joining
      activity, and the high mobility group chromosomal protein A1 might approximate
      both long terminal repeat (LTR) ends and facilitate integrase binding by
      unwinding the LTR termini. Furthermore, the lens-epithelium-derived growth factor
      (LEDGF; also known as p75) seems to tether HIV-1 integrase to the chromosomes.
      Although a direct role in integration has only been demonstrated for LEDGF/p75,
      to date, each validated cellular co-factor for HIV-1 integration could constitute
      a promising new target for antiviral therapy.

PMID- 16403636
TI  - Genomic DNA methylation: the mark and its mediators.
AB  - Methylation of DNA at position five of the cytosine ring occurs at most CpG
      dinucleotides in the mammalian genome and is essential for embryonic viability.
      With several of the key proteins now known, it has become possible to approach
      the biological significance of this epigenetic system through both biochemistry
      and genetics. As a result, advances have been made in our understanding of the
      mechanisms by which DNA methylation is targeted to specific regions of the genome
      and interpreted by methyl-CpG-binding proteins. Recent studies have illuminated
      the role of DNA methylation in controlling gene expression and have strengthened
      its links with histone modification and chromatin remodelling.

PMID- 16403637
TI  - A convex lateral tibial plateau for knee replacement.
AB  - Unicompartmental knee replacements have not performed as well in the lateral
      compartment as in the medial. This may be because the tibial components have flat
      or slightly concave surfaces which match the medial plateau but not the convex
      lateral plateau. The aim of this study was to find the optimal radius for a
      convex lateral tibial component. Twelve normal lateral tibial plateau were
      retrieved at knee replacement, and their surface contour in their mid sagittal
      plane was determined. The optimal circle was fitted and its radius measured. A
      series of different shaped tibial components were superimposed. From published
      information about the position of the femoral condyle relative to the tibia in
      different degrees of flexion, the flexion gap at these angles was determined. The
      average radius of the lateral tibial plateau was 40 mm. However, as the surface
      was polyradial it was not clear if this average radius would be optimal. In full
      flexion, a flat tibial plateau distracted the knee by 8 mm (p<0.001). A 75 mm
      radius spherical tibial plateau did not alter the knee kinematics significantly
      and gave rise to a change in joint distraction of 1.5 mm. Spherical tibial
      plateau of 50 mm and 25 mm radii significantly altered knee kinematics (p<0.001)
      and resulted in changes in distraction of 3 mm and 4 mm respectively. The optimal
      shape for a unicompartmental lateral tibial plateau is likely to be a spherical
      dome with radius of about 75 mm. The incorporation of this shape in the lateral
      side of a total knee replacement might improve its flexion.

PMID- 16403638
TI  - Syntheses of glucose analogues of E5564 as a highly potent anti-sepsis drug
      candidate.
AB  - Glucose analogues 5 and 9 of E5564 were synthesized, and their LPS-antagonistic
      activities were measured. The inhibitory activities (IC50) on LPS-induced
      TNFalpha production of these two compounds towards human whole blood cells were
      0.06 and 0.83 nM, respectively. Inhibitory doses (ID50) of compounds 5 and 9 on
      TNFalpha production induced by coinjection of galactosamine and LPS in C3H/HeN
      mice in vivo were measured and were 0.55 and <0.20 mg/kg, respectively. And also
      C3H/HeN mice preinjected with compounds 5 and 9 were protected from lethality
      induced by coinjection of galactosamine and LPS; out of eight mice preinjected
      with 1 mg/kg of the compounds, one-six and three of eight mice were protected,
      respectively.

PMID- 16403639
TI  - Mechanism of the Class I KDPG aldolase.
AB  - In vivo, 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase catalyzes the
      reversible, stereospecific retro-aldol cleavage of KDPG to pyruvate and D
      glyceraldehyde-3-phosphate. The enzyme is a lysine-dependent (Class I) aldolase
      that functions through the intermediacy of a Schiff base. Here, we propose a
      mechanism for this enzyme based on crystallographic studies of wild-type and
      mutant aldolases. The three dimensional structure of KDPG aldolase from the
      thermophile Thermotoga maritima was determined to 1.9A. The structure is the
      standard alpha/beta barrel observed for all Class I aldolases. At the active site
      Lys we observe clear density for a pyruvate Schiff base. Density for a sulfate
      ion bound in a conserved cluster of residues close to the Schiff base is also
      observed. We have also determined the structure of a mutant of Escherichia coli
      KDPG aldolase in which the proposed general acid/base catalyst has been removed
      (E45N). One subunit of the trimer contains density suggesting a trapped pyruvate
      carbinolamine intermediate. All three subunits contain a phosphate ion bound in a
      location effectively identical to that of the sulfate ion bound in the T.
      maritima enzyme. The sulfate and phosphate ions experimentally locate the
      putative phosphate binding site of the aldolase and, together with the position
      of the bound pyruvate, facilitate construction of a model for the full-length
      KDPG substrate complex. The model requires only minimal positional adjustments of
      the experimentally determined covalent intermediate and bound anion to
      accommodate full-length substrate. The model identifies the key catalytic
      residues of the protein and suggests important roles for two observable water
      molecules. The first water molecule remains bound to the enzyme during the entire
      catalytic cycle, shuttling protons between the catalytic glutamate and the
      substrate. The second water molecule arises from dehydration of the carbinolamine
      and serves as the nucleophilic water during hydrolysis of the enzyme-product
      Schiff base. The second water molecule may also mediate the base-catalyzed
      enolization required to form the carbon nucleophile, again bridging to the
      catalytic glutamate. Many aspects of this mechanism are observed in other Class I
      aldolases and suggest a mechanistically and, perhaps, evolutionarily related
      family of aldolases distinct from the N-acetylneuraminate lyase (NAL) family.

PMID- 16403640
TI  - Novel fluorescent markers for hypoxic cells of naphthalimides with two
      heterocyclic side chains for bioreductive binding.
AB  - Novel naphthalimides with two heterocyclic side chains of 2-nitroimidazole for
      bioreductive binding were designed, synthesized, and used as fluorescent markers
      for hypoxic cells. Their evaluation for imaging tumor hypoxia was carried out in
      V79 cells, CHO cells, and 95D cells in vitro by using fluorescence scan ascent.
      A2 and A4 showed a very large differential fluorescence between hypoxic and oxic
      cells (V79 cells) in vitro and are promising candidate markers for hypoxic cells.

PMID- 16403641
TI  - Interaction of arylpiperazine ligands with the hydrophobic part of the 5-HT1A
      receptor binding site.
AB  - A flexible docking of a series of arylpiperazine derivatives with structurally
      different aryl part to the binding site of a model of human 5-HT1A receptor was
      exercised. The influence of structure and hydrophobic properties of aryl moiety
      on binding affinities was discussed and a model for ligand binding in the
      hydrophobic part of the binding site was proposed.

PMID- 16403642
TI  - Synthesis and CB1 receptor activities of dimethylheptyl derivatives of 2
      arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE).
AB  - Results from a factor analysis and activity studies of commercially available
      endocannabinoid-type compounds set the starting point for the current study where
      dimethylheptyl (DMH) analogues of two endocannabinoids, 2-arachidonoyl glycerol
      (2-AG) and 2-arachidonyl glyceryl ether (2-AGE), were synthesized and their
      ability to activate the CB1 receptors was determined by the [35S]GTPgammaS
      binding assay using rat cerebellar membranes. The main goal of the study was to
      examine how the DMH end tail affects the activity properties of 2-AG (1) and its
      stable ether (2) and urea analogues (5). The importance of the chain length was
      also explored by synthesizing 2-AG and 2-AGE derivatives (3 and 4) possessing the
      chain length C21 instead of C22. Replacement of the pentyl end chain with the DMH
      resulted in distinct potency decrease as compared to the reference compounds. The
      modification did not have such a strong impact on the efficacy values. In fact,
      the efficacy of the derivatives of 2-AGE (2 and 4) was comparable or even
      improved. Introducing a more stable and hydrophilic urea bond led to a dramatic
      decrease in biological activity.

PMID- 16403643
TI  - Synthesis and photo-induced DNA cleaving activities of conjugates of halophenyl
      derivative and polyamide containing N-methylimidazoles.
AB  - Halophenyl derivatives were linked to different termini of polyamide containing
      three imidazole rings to give novel conjugates for examining the influence of the
      location of linking on DNA-cleavage efficiency. The DNA cleavage activities of
      the conjugates were compared on supercoiled DNA (pBluescript SK) under UV
      irradiation at 365 nm. It was found that bromophenyl-ImImImbetaDp (2), which is
      the conjugate of bromophenyl motif directly linked to the N-terminus of
      polyamide, had the highest photocleavage efficiency among six novel conjugates.
      In addition, it was found that the polyamide containing three N-methylimidazole
      rings could greatly enhance the photocleavage efficiency of these conjugates.

PMID- 16403644
TI  - Nicotinic activity stabilizes convergence of nicotinic and GABAergic synapses on
      filopodia of hippocampal interneurons.
AB  - Nicotinic acetylcholine receptors containing alpha7 subunits occupy pre- and
      postsynaptic sites in the adult hippocampus. We find that embryonic hippocampal
      slices in culture display the receptors most prominently on interneurons where
      they form clusters localized in part on filopodia. The receptors often co
      distribute specifically with GABAA receptors. In septal-hippocampal co-cultures,
      the filopodia become co-innervated by cholinergic and GABAergic terminals
      abutting the receptor clusters. Nicotinic transmission appears to stabilize the
      cholinergic contacts: pharmacological blockade of the alpha7-containing nicotinic
      receptors increases the rate of filopodia movement and decreases the incidence of
      the clusters being adjacent to cholinergic terminals. Immunostaining fresh
      hippocampal slices from neonatal rat pups confirms that cholinergic and GABAergic
      terminals contact alpha7-containing nicotinic receptor clusters in vivo, and the
      clusters appear to include filopodial sites. The results indicate a convergence
      of nicotinic and GABAergic input at specific sites on developing hippocampal
      interneurons and suggest that synaptic activity helps stabilize the nicotinic
      contribution.

PMID- 16403645
TI  - Codon optimization, expression, and characterization of an internalizing anti
      ErbB2 single-chain antibody in Pichia pastoris.
AB  - Anti-ErbB2 antibodies are used as convenient tools in exploration of ErbB2
      functional mechanisms and in treatment of ErbB2-overexpressing tumors. When we
      employed the yeast Pichia pastoris to express an anti-ErbB2 single-chain antibody
      (scFv) derived from the tumor-inhibitory monoclonal antibody A21, the yield did
      not exceed 1-2 mg/L in shake flask cultures. As we considered that the poor codon
      usage bias may be one limiting factor leading to the inefficient translation and
      scFv production, we designed and synthesized the full-length scFv gene by
      choosing the P. pastoris preferred codons while keeping the G+C content at
      relatively low level. Codon optimization increased the scFv expression level 3-
      to 5-fold and up to 6-10 mg/L. Northern blotting further confirmed that the
      increase of scFv expression was mainly due to the enhancement of translation
      efficiency. Investigation of culture conditions revealed that the maximal cell
      growth and scFv expression were achieved at pH 6.5-7.0 with 2% casamino acids
      after 72 h methanol induction. Secreted scFv was easily purified (>95%
      homogeneous product) from culture supernatants in one step by using Ni2+
      chelating affinity chromatography. The yield was approximately 10-15 mg/L.
      Functional studies showed that the A21 scFv could be internalized with high
      efficiency after binding to the ErbB2-overexpressing cells, suggesting this
      regent may prove especially useful for ErbB2-targeted immunotherapy.

PMID- 16403646
TI  - Protein expression enhancement in efflux-deleted mutant bacteria.
AB  - We applied a single-cell assay to characterize how transcription dynamics affects
      protein expression levels of a tetracycline-inducible gene expression system.
      Transcriptional activity of the tetracycline promoter in response to a steady
      level of inducer is steady in DeltaacrAB efflux mutant but pulsating in wildtype
      Escherichia coli cells. We found that the expression level of the green
      fluorescent protein is several folds higher in DeltaacrAB efflux mutant than in
      wildtype cells.

PMID- 16403647
TI  - Heterologous expression of dodecaheme "nanowire" cytochromes c from Geobacter
      sulfurreducens.
AB  - Multiheme cytochromes c are difficult to produce in heterologous systems. The
      genome of delta-proteobacterium Geobacter sulfurreducens contains more than a
      hundred genes coding for c-type cytochromes. Among those are two dodecaheme
      cytochromes c representing a new class of multiheme cytochromes, whose putative
      structure is a one-dimensional array of small highly homologous domains that
      contain three hemes and are covalently bound by short linkers. They are likely to
      form "nanowires" that are part of the electron transfer chain. We cloned the
      genes coding for the two cytochromes into a vector we developed for ligation
      independent cloning of proteins targeted to the Escherichia coli periplasmic
      space. We expressed the proteins in E. coli co-transformed with a plasmid
      harboring the cytochrome c maturation genes. Expression levels were optimized by
      varying IPTG concentrations used for induction. Although both proteins appeared
      insoluble or strongly associated with cell membranes, they were solubilized using
      0.5 M sodium chloride which was more selective than conventional solubilizing
      agents, such as HEGA-10 or beta-octylglucoside. The solubilized proteins were
      dialyzed and purified by cation exchange chromatography followed by gel
      filtration. Mass-spectrometry analysis confirmed that both purified proteins
      contained the complete set of covalently attached hemes, 12 per molecule. Their
      visible spectra were typical of c-type cytochromes. Both proteins were
      successfully crystallized.

PMID- 16403648
TI  - Overproduction in Escherichia coli and purification of Epstein-Barr virus EBNA-1.
AB  - Epstein-Barr virus nuclear antigen 1 (EBNA-1) is a multi-functional protein of
      the Epstein-Barr virus (EBV). Due to its low abundance in EBV-transformed cells,
      overproduction in a foreign host is preferred to obtain purified EBNA-1 protein.
      The EBNA-1 gene possesses a large number of Escherichia coli rare codons (23%).
      By using E. coli BL21(DE3)Rosetta2 cells that augment the low-abundance tRNA
      genes, the expression level of EBNA-1 in E. coli was greatly enhanced. EBNA-1 was
      then purified by applying the whole cell extract soluble fraction to a Ni-NTA
      Superflow column and eluting with an imidazole gradient. The improved
      overexpression in E. coli followed by a one-step Ni-NTA purification resulted in
      a sufficient amount of pure EBNA-1 protein to test DNA binding activity, and
      prepare and test EBNA-1-specific monoclonal antibodies (mAbs).

PMID- 16403649
TI  - Improving protein solubility: the use of the Escherichia coli dihydrofolate
      reductase gene as a fusion reporter.
AB  - We have devised a strategy for screening mutant libraries for enzyme variants
      with enhanced solubility. The method is based on the observation that Escherichia
      coli can become insensitive to the antibiotic trimethoprim (TMP) if dihydrofolate
      reductase (DHFR) is expressed at an appropriate level. DHFR is a very soluble
      protein and can be expressed at levels that exceed normally lethal concentrations
      of TMP. In our approach, the gene encoding an insoluble target protein is placed
      in a vector so that the translated protein will be fused to DHFR. The resulting
      fusion protein will form inclusion bodies and inactivate DHFR-the cells will be
      susceptible to TMP. Mutations to the target protein that make it more soluble
      will also make the fusion protein more soluble so that DHFR will be at least
      partially active-the cells will be resistant to TMP. As the solubility of the
      target protein increases, the cells will become more resistant to TMP. The system
      was tested with a putative acetyltransferase (ACE) from a strain of the marine
      bacterium Vibrio fischerii. The gene encoding this protein was of interest since
      it is part of a mobile gene cassette within an integron array of the strain in
      question. After multiple rounds of shuffling and selection, ACE mutants were
      produced that had significantly improved solubility.

PMID- 16403650
TI  - Regarding "caffeine metabolism, genetics, and perinatal outcomes: a review of
      exposure assessment considerations during pregnancy".

PMID- 16403652
TI  - Electromechanical imaging of biomaterials by scanning probe microscopy.
AB  - The majority of calcified and connective tissues possess complex hierarchical
      structure spanning the length scales from nanometers to millimeters.
      Understanding the biological functionality of these materials requires reliable
      methods for structural imaging on the nanoscale. Here, we demonstrate an approach
      for electromechanical imaging of the structure of biological samples on the
      length scales from tens of microns to nanometers using piezoresponse force
      microscopy (PFM), which utilizes the intrinsic piezoelectricity of biopolymers
      such as proteins and polysaccharides as the basis for high-resolution imaging.
      Nanostructural imaging of a variety of protein-based materials, including tooth,
      antler, and cartilage, is demonstrated. Visualization of protein fibrils with sub
      10nm spatial resolution in a human tooth is achieved. Given the near-ubiquitous
      presence of piezoelectricity in biological systems, PFM is suggested as a
      versatile tool for micro- and nanostructural imaging in both connective and
      calcified tissues.

PMID- 16403651
TI  - Anisotropic lattice distortions in the mollusk-made aragonite: a widespread
      phenomenon.
AB  - In this paper, we present experimental results demonstrating systematic
      structural distinctions between biogenic and non-biogenic calcium carbonate.
      Specifically we show, by high-resolution X-ray powder diffraction on dedicated
      synchrotron beam lines, that the orthorhombic unit cell of the mollusk-made
      aragonite is anisotropically distorted as compared with that one of geological
      aragonite. In all investigated shells, belonging to different classes (bivalve,
      gastropod, and cephalopod) and taken from different habitat origins (sea, fresh
      water, and land), the maximum elongation of about 0.1-0.2% was found along the c
      axis. The lattice distortions along the a-axis were also of the positive sign
      (elongation) but lower than those along the c-axis, whereas lattice distortions
      along the b-axis were always negative (contraction). Supporting experiments,
      including structural analysis after a bleach procedure, measurements of
      temperature-dependent lattice relaxation, measurements of the CO(2) release at
      elevated temperatures, signify that the observed structural distinctions are most
      probably caused by the organic molecules intercalating into the aragonite lattice
      during biomineralization. Our findings show that in some sense organisms control
      the atomic structure of the crystals. Deeper understanding of this phenomenon
      will aid in the development of new approaches to grow biomimetic composites and
      tailor their properties on a molecular level.

PMID- 16403653
TI  - Scaling and non-scaling of muscle activity, kinematics, and dynamics in sit-ups
      with different degrees of difficulty.
AB  - The purpose of this study was to investigate how the CNS adjusts motor patterns
      for variants of a complex axial movement-the sit-up. Adjustments were induced by
      changing the support surface contact and mass distribution of the body. Healthy
      adults performed straight-legged sit-ups, 3 s in duration, with support added to
      or removed from the lumbar trunk, or with mass added to the head or to the legs.
      Each of these interventions either increased or decreased the difficulty of the
      task. The study addressed the extent to which changes in sit-up difficulty are
      compensated by scaling of muscle activity, kinematics, and dynamics versus the
      extent to which they are compensated by changing discretely the motor pattern.
      The analysis of muscle activity, kinematics, and dynamics focused on the first 30
      40% of the sit-up-the trunk flexion phase-since this is the most critical part of
      the movement. Our results demonstrate that, in some respects, sit-up kinematics
      and dynamics scaled with difficulty, but in other respects, they did not. Muscle
      activity also scaled, in many respects, but in more difficult sit-ups, abdominal
      flexor activity decreased instead of increased. Non-scaling changes in these
      parameters suggest that complex movements, such as the sit-up, may require
      discrete changes in motor pattern in order to deal with large loads, which
      challenge the available leverage.

PMID- 16403655
TI  - Phenomenology and delusions: who put the 'alien' in alien control?
AB  - Although current models of delusion converge in proposing that delusions are
      based on unusual experiences, they differ in the role that they accord experience
      in the formation of delusions. On some accounts, the experience comprises the
      very content of the delusion, whereas on other accounts the delusion is adopted
      in an attempt to explain an unusual experience. We call these the endorsement and
      explanationist models, respectively. We examine the debate between endorsement
      and explanationist models with respect to the 'alien control' delusion. People
      with delusions of alien control believe that their actions and/or thoughts are
      being controlled by an external agent. Some accounts of alien control (e.g., )
      are best thought of in explanationist terms; other accounts (e.g., ) seem more
      suited to an endorsement approach. We argue that recent cognitive and
      neurophysiological evidence favours an endorsement model of the delusion of alien
      control.

PMID- 16403654
TI  - Are "implicit" attitudes unconscious?
AB  - A widespread assumption in recent research on attitudes is that self-reported
      (explicit) evaluations reflect conscious attitudes, whereas indirectly assessed
      (implicit) evaluations reflect unconscious attitudes. The present article reviews
      the available evidence regarding unconscious features of indirectly assessed
      "implicit" attitudes. Distinguishing between three different aspects of
      attitudes, we conclude that (a) people sometimes lack conscious awareness of the
      origin of their attitudes, but that lack of source awareness is not a
      distinguishing feature of indirectly assessed versus self-reported attitudes, (b)
      there is no evidence that people lack conscious awareness of indirectly assessed
      attitudes per se, and (c) there is evidence showing that, under some conditions,
      indirectly assessed (but not self-reported) attitudes influence other
      psychological processes outside of conscious awareness. Implications for the
      concept of "implicit attitudes" are discussed.

PMID- 16403656
TI  - The multiscale character of evoked cortical activity.
AB  - Both the architecture and the dynamics of the brain have characteristic features
      at different spatial scales. However, the existence, nature and function of
      dynamical interdependencies between such scales have not been investigated. We
      studied the multiscale properties of functional magnetic resonance imaging (fMRI)
      data acquired while human subjects viewed a visual image. Traditional "region of
      interest" analysis of this data set revealed evoked activity in primary and
      extrastriate visual cortex. Wavelet transform in the spatial domain provides a
      multiscale representation of this evoked brain activity. Studying the correlation
      structure of this representation revealed strong and novel interdependencies in
      these data within and between different spatial scales. We found that such
      correlations are stronger than those evident in the original data and comparable
      in magnitude to those obtained after Gaussian smoothing. However, analysis of the
      data in the wavelet domain revealed additional structure such as positive
      correlations, strong anti-correlations and phase-lagged interdependencies.
      Statistical significance of these effects was inferred through nonparametric
      bootstrap techniques. We conclude that the spatial analysis of functional
      neuroimaging data in the wavelet domain provides novel information which may
      reflect complex spatiotemporal neuronal activity and information encoding. It
      also affords a quantitative means of testing hierarchical and multiscale models
      of cortical activity.

PMID- 16403657
TI  - The impact of intragenic recombination on phylogenetic reconstruction at the
      sectional level in Eucalyptus when using a single copy nuclear gene (cinnamoyl
      CoA reductase).
AB  - Low copy number nuclear genes have been found to be useful for phylogenetic
      reconstruction at different taxonomic levels. This study investigated the utility
      of a single copy gene, cinnamoyl CoA reductase (CCR), for resolving phylogenetic
      relationships at the sectional level within Eucalyptus. The monophyly of sections
      Exsertaria and Latoangulatae was explored, using section Maidenaria as an
      outgroup, and the impact of intragenic recombination on phylogenetic
      reconstruction examined. Phylogenetic analysis did not resolve monophyletic
      groups. Latoangulatae and Maidenaria were polyphyletic or paraphyletic.
      Exsertaria species formed a clade but included a single Latoangulatae species (E.
      major). Recombination analysis identified two intragenic recombination events
      that involved species from different sections, which have probably been
      facilitated by inter-sectional hybridisation. One of the events most likely
      occurred prior to speciation, with several Latoangulatae species having the
      recombinant allele. The other event may have occurred after speciation, since
      only one of two E. globulus samples possessed the recombinant allele. This is the
      first detailed report of intragenic recombination in both CCR and Eucalyptus, and
      between species of different sections of a plant genus. The occurrence of
      intragenic recombination may explain the anomalous positions of some species
      within the phylogenetic tree, and indicates that phylogenetic analysis of
      Eucalyptus using nuclear genes will be problematic unless recombination is taken
      into account.

PMID- 16403658
TI  - Phylogenetic relationships of Oriental torrent frogs in the genus Amolops and its
      allies (Amphibia, Anura, Ranidae).
AB  - We investigated the phylogenetic relationships among 20 species of Oriental
      torrent frogs in the genus Amolops and its allies from China and Southeast Asia
      based on 1346-bp sequences of the mitochondrial 12S and 16S rRNA genes. Oriental
      species of the tribe Ranini form a monophyletic group containing 11 clades (Rana
      temporaria + Pseudoamolops, R. chalconota, four clades of Amolops, Meristogenys,
      three clades of Huia species, and Staurois) for which the phylogenetic
      relationships are unresolved. The genus Amolops consists of southern Chinese,
      southwestern Chinese, Thai, and Vietnamese-Malaysian lineages, but their
      relationships are also unresolved. The separation of southern and southwestern
      lineages within China conforms to previous morphological and karyological
      results. Species of Huia do not form a monophyletic group, whereas those of
      Meristogenys are monophyletic. Because P. sauteri is a sister species of R.
      temporaria, distinct generic status of Pseudoamolops is unwarranted.

PMID- 16403659
TI  - Why iron-dithiocarbamates ensure detection of nitric oxide in cells and tissues.
AB  - The in vivo mechanism of NO trapping by iron-dithiocarbamate complexes is
      considered. Contrary to common belief, we find that in biological systems the NO
      radicals are predominantly trapped by ferric iron-dithiocarbamates. Therefore,
      the trapping leads to ferric mononitrosyl complexes which are diamagnetic and
      cannot be directly detected with Electron Paramagnetic Resonance spectroscopy.
      The ferric mononitrosyl complexes are far easily reduced to ferrous state with L
      cysteine, glutathione, ascorbate or dithiocarbamate ligands than their non
      nitrosyl counterpart. When trapping NO in oxygenated biological systems, the
      majority of trapped nitric oxide is found in diamagnetic ferric mononitrosyl iron
      complexes. Only a minority fraction of NO is trapped in the form of paramagnetic
      ferrous mononitrosyl iron complexes with dithiocarbamate ligands. Subsequent ex
      vivo reduction of biological samples sharply increases the total yield of the
      paramagnetic mononitrosyl iron complexes. Reduction also eliminates the
      overlapping EPR spectrum from Cu(2+)-dithiocarbamate complexes. This facilitates
      the quantification of yields from NO trapping.

PMID- 16403660
TI  - Catalase protects cardiomyocytes via its inhibition of nitric oxide synthesis.
AB  - Nitric oxide (NO) has been reported to play an important role as an effector
      molecule in cytokine signal transduction in cardiomyocytes. A treatment of
      neonatal rat ventricular cardiomyocytes with interleukin-1 beta (IL-1beta), tumor
      necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) induces
      apoptosis via an NO-dependent pathway. However, cardiomyocytes were more
      resistant to NO-dependent cell death in the presence of catalase, while producing
      inducible nitric oxide synthase. This paper reports that catalase stimulates the
      NF-kappaB-binding affinity. However, the NO synthase activity is abolished by the
      addition of catalase, suggesting that H(2)O(2) is involved in NO synthesis in a
      posttranslation state. The catalase-induced inhibition of NO was partially but
      significantly reversed by H(4)B, an important cofactor of NO synthesis. Treatment
      of myocytes with IL-1beta, TNF-alpha, and IFN-gamma induced a significant
      increase in the formation of peroxynitrite, and a pretreatment with catalase was
      found to quench the production of peroxynitrite. This paper shows that the
      catalase activity was significantly down-regulated by H(4)B in a concentration
      dependent manner. The treatment of H(4)B induced reactive oxygen species (ROS)
      release in cardiac cell system. These results suggest that catalase interferes
      with NO and peroxynitrite production as well as with the related apoptosis of
      cardiomyocytes. This study also shows that the catalase-induced inhibition of NO
      release may be reversed by H(4)B by the release of ROS.

PMID- 16403661
TI  - Studies on nitric oxide synthase activity in haemocytes of shrimps Fenneropenaeus
      chinensis and Marsupenaeus japonicus after white spot syndrome virus infection.
AB  - The nitric oxide synthase (NOS) activity in the haemocytes of shrimps
      Fenneropenaeus chinensis (Osbeck) and Marsupenaeus japonicus (Bate) was studied
      after white spot syndrome virus (WSSV) infection to determine its characteristics
      in response to virus infection. First, the NOS activity in haemocytes of shrimps
      was determined by the means of NBT reduction and changes in cell conformation.
      And the variations of NOS activity in shrimps after challenge with WSSV
      intramuscularly were evaluated through the analysis of L-citrulline and total
      nitrite/nitrate (both as NO derivates) concentrations. The result showed that NOS
      activity in the haemocytes of F. chinensis increased slightly from 0 to 12h
      postchallenge, indicated by the variations of l-citrulline (from 11.15+/-0.10 to
      12.08+/-0.64 microM) and total nitrite/nitrate concentrations (from 10.45+/-0.65
      to 12.67+/-0.52 microM). Then it decreased sharply till the end of the experiment
      (84 h postchallenge), the concentrations of l-citrulline and total
      nitrite/nitrate at 84 h were 1.58+/-0.24 and 2.69+/-0.70 microM, respectively.
      The LPS-stimulated NOS activity kept constant during the experiment. However, in
      M. japonicus, the NOS activity kept increasing during the first 72 h
      postchallenge, the concentrations of l-citrulline and total nitrite/nitrate
      increased from 7.82+/-0.77 at 0 h to 10.79+/-0.50 microM at 72 h, and from 8.98+/
      0.43 at 0 h to 11.20+/-0.37 microM at 72 h, respectively. Then it decreased till
      the end of the experiment (216 h postchallenge), and the concentrations of l
      citrulline and total nitrite/nitrate at 216 h were 5.66+/-0.27 and 4.68+/-0.16
      microM, respectively. More importantly, an apparent increase of LPS-stimulated
      NOS activity was observed in M. japonicus at 48 h postchallenge, which was about
      4 times higher than that in the control group of health shrimps. In
      correspondence with the difference of NOS activity between the two species of
      shrimps, the cumulative mortalities of the shrimps were also different. All
      shrimps of F. chinensis in the mortality experiment died in 66 h, much more
      quickly than M. japonicus, whose accumulative mortality reached 100% after 240 h.
      Data here reported let us hypothesize that NOS activity in the haemocytes of
      shrimps F. chinensis and M. japonicus responses to WSSV infection differently,
      and this might be one of the reasons for the different susceptibility of F.
      chinensis and M. japonicus to WSSV infection.

PMID- 16403662
TI  - The course of high-sensitive C-reactive protein in correlation with pain and
      clinical function in patients with acute lumbosciatic pain and chronic low back
      pain - a 6 months prospective longitudinal study.
AB  - In this prospective longitudinal study with a follow-up of 6 months, the course
      of serum concentration of C-reactive protein was measured by an ultrasensitive
      immunoassay in 31 patients with acute lumbosciatic pain and 41 patients with
      chronic low back pain. High-sensitive CRP (hsCRP), pain and clinical function
      were assessed at ten fixed time-points during follow-up. The course of hsCRP
      values was assessed in relation to the course of pain and clinical function
      adjusting for possible confounding factors. At the beginning of the study, there
      were no statistically significant differences in mean hsCRP levels in patients
      with acute lumbosciatic pain (1.49mg/l) compared to the levels obtained in
      patients with chronic low back pain (1.30mg/l) and those in a control group from
      the general population (1.26mg/l). In patients with acute lumbosciatic pain,
      hsCRP declined significantly in the initial period of 3 weeks with a
      corresponding decrease in pain and improvement in function and clinical
      evaluation as assessed with the straight leg raising test (SLR), whereas after
      this period, the course of the hsCRP did not correspond with the clinical
      parameters. In patients with chronic low back pain, hsCRP remained approximately
      constant throughout the whole period with no correlation with pain or function.
      As a conclusion, according to this study levels of hsCRP do not have a major
      clinical relevance when evaluating the long-term course of patients with acute
      lumbosciatic pain and chronic low back pain and therefore should not be taken
      into primary consideration when decisions on therapy are made.

PMID- 16403663
TI  - No role for inhaled magnesium sulfate in the treatment of acute asthma?

PMID- 16403664
TI  - The role of vascular and hormonal genes in migraine susceptibility.
AB  - Migraine is a primary headache disorder that involves both genetic and
      environmental components. Migraine is considered to be a polygenic disorder with
      a number of susceptibility genes having a minor but nonetheless significant
      impact on susceptibility. Migraine candidate gene studies have concentrated
      mainly on genes involved in neurotransmitter pathways, however evidence also
      exists for a role for alterations in vascular and hormonal function in migraine
      susceptibility. We present here a mini-review of genetic studies, investigating
      the potential role of vascular and hormonal gene variants, and discuss how
      vascular and hormonal dysfunction may impact on migraine susceptibility. We
      propose that the potential role of vascular and hormonal genes in this disorder
      warrants further investigation.

PMID- 16403665
TI  - New frontiers in hereditary metabolic disease: an historical perspective.

PMID- 16403666
TI  - Expression of monocarboxylate transporter 4 in human platelets, leukocytes, and
      tissues assessed by antibodies raised against terminal versus pre-terminal
      peptides.
AB  - We compared antibodies (Abs) raised in rabbits against two non-overlapping
      peptides, terminal (T) and pre-terminal (PT) of the human monocarboxylate
      transporter (MCT4) lactate transporter in a variety of human tissues. Upon
      stringent SDS extraction, the PT Ab recognized a major 32 kDa band in many
      tissues, but not in leukocytes, while the T Ab recognized a 45 kDa band in
      leukocytes but only in a few other tissues. In two cell lines, human adult
      retinal pigment epithelial and Madin-Darby canine kidney, however, both Abs
      identified the same 45 kDa band only, whether extracted by stringent SDS or by a
      mild Triton X-100 procedure. Applying Triton X-100 and milder SDS methods to
      human tissues led us to conclude that: (1) MCT4 is more labile to proteolysis
      than MCT1 or 2; (2) the proteolysis involves an enzyme system which is absent
      from the cell lines, is of variable content in human tissues, and is accelerated
      by SDS and/or heat; (3) a major product is the 32 kDa band, which is missing the
      C-terminal peptide, since it is seen by the Ab to MCT4-PT, but not the Ab to MCT4
      T; (4) this truncated 32 kDa form is prone to aggregate, producing oligomers also
      detected only by the MCT4-PT; (5) the 32 kDa form may have a physiological
      function, since (except in the cell lines and monocytes) it is the major form
      seen with the PT Ab even with our mildest extractions, and since MCT4-PT stained
      two compartments that were not stained by the T Ab in our immunohistochemistry
      survey: the capsule of the muscle spindle, and the cytoplasm of the lymphocyte;
      (6) platelets contained MCT4, stained by both Abs, and verified by the 45kDa band
      on Western blotting, in addition to the presence of MCT2 that we had demonstrated
      previously [N. Merezhinskaya, S.A. Ogunwuyi, F.G. Mullick, W.N. Fishbein,
      Presence and localization of three lactic acid transporters (MCT1, -2, and -4) in
      separated human granulocytes, lymphocytes, and monocytes, J. Histochem. Cytochem.
      52 (2004) 1483-1493.

PMID- 16403667
TI  - [Surgeons! Pity patients who suffer from endometriosis!].

PMID- 16403668
TI  - [Neurological outcome of children from twin pregnancies. Gynecol Obstet Fertil
      2005;33:563-9].

PMID- 16403669
TI  - [Tocolysis with nifedipine: its use in current practice. Gynecol Obstet Fertil
      2005;33:483-7].

PMID- 16403670
TI  - Imaging aspects and non-surgical interventional treatment in human alveolar
      echinococcosis.
AB  - Alveolar echinococcosis (AE) of the liver caused by the metacestode of the fox
      tapeworm Echinococcus multilocularis is characterized by a multivesicular
      structure surrounded by an extensive fibro-inflammatory host reaction. The
      lesions behave like a slow-growing liver cancer, without sharp limits between the
      parasitic tissue and the liver parenchyma. Invasion of biliary and vascular walls
      is another hallmark of this severe disease. Moreover, the poor vascularization of
      the parasitic mass often leads to necrosis in the central part of the lesion.
      This explains why liver abscess due to superimposed bacterial infection of the
      necrotic area may occur in this disease. Currently, a range of imaging techniques
      can be used at the different stages of management of AE. For diagnosis,
      ultrasonography remains the first line examination. For a more accurate disease
      evaluation, aiming to guide the surgical strategy, computerized tomography,
      Magnetic Resonance (MR) imaging, including cholangio-MR imaging are of
      importance, providing useful complementary information. More recently, Positive
      Emission Tomography using [18F] fluoro-deoxyglucose has been developed for the
      follow-up of inoperable AE patients under long-term benzimidazoles therapy. This
      approach seems very promising to assess inflammatory activity and thereby to
      indirectly depict parasitic activity. Non-surgical interventional procedures,
      mainly percutaneous biliary and/or centro-parasitic abscesses drainages, are
      currently a major aspect in the care of incurable AE patients and have largely
      contributed to the improvement of survival in this situation during the past 20
      years. They may also be used as a bridge before a curative surgical procedure in
      symptomatic patients presenting a life-threatening bacterial and/or fungal
      infection. It is also very useful in inoperable patients to overcome similar
      infectious episodes.

PMID- 16403671
TI  - Effects of arachidonic acid analogs on FcepsilonRI-mediated activation of mast
      cells.
AB  - Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) have been shown
      to modulate a number of inflammatory disorders. Mast cells play a critical role
      in the initiation and maintenance of inflammatory responses. However, the effects
      of PUFAs on mast cell functions have not been fully addressed. We here-in
      examined the effects of PUFAs on the high affinity IgE receptor (FcepsilonRI)
      mediated mast cell activation using RBL-2H3 cells, a rat mast cell line, that
      were cultured in the medium containing palmitic acid (PA), AA, or the AA analogs
      mead acid (MA) and eicosapentaenoic acid (EPA). In AA-supplemented cells, the
      FcepsilonRI-mediated beta-hexosamidase and TNF-alpha release, calcium (Ca(2+))
      influx, and some protein tyrosine phosphorylations including Syk and linker for
      activation of T cells (LAT) were enhanced, whereas, in MA- or PA-supplemented
      cells, they were not changed when compared with cells cultured in control medium.
      In EPA-supplemented cells, the enhancements of beta-hexosamidase release and
      protein tyrosine phosphorylations were observed. Furthermore, in AA- or EPA
      supplemented cells, FcepsilonRI-mediated intracellular production of reactive
      oxygen species (ROS) that is required for the tyrosine phosphorylation of LAT and
      Ca(2+) influx were enhanced when compared with the other cells. Thus,
      preincubation of AA or EPA augmented FcepsilonRI-mediated degranulation in mast
      cells by affecting early events of FcepsilonRI signal transduction, which might
      be associated with the change of fatty acid composition of the cell membrane and
      enhanced production of ROS. The results suggest that some PUFAs can modulate
      FcepsilonRI-mediated mast cell activation and might affect FcepsilonRI/mast cell
      mediated inflammation, such as allergic reaction.

PMID- 16403672
TI  - Neuromagnetic responses to vowels vs. tones reveal hemispheric lateralization.
AB  - OBJECTIVE: To evaluate whether a simple auditory paradigm could demonstrate a
      difference in cortical lateralization between right- and left-handed subjects.
      Such information would be important for later development of clinical noninvasive
      tests of hemispheric language dominance in candidates for brain surgery. METHODS:
      Healthy subjects (10 strongly right-handed, 10 strongly left-handed, 5 weakly
      right-handed, and two ambidextrous) listened to binaural pairs of tones and pairs
      of Finnish vowels and decided whether the items in the pair were the same (target
      probability 20%). Cortical responses were recorded with whole-scalp
      magnetoencephalography. RESULTS: The laterality index for strengths of the
      auditory-cortex 100 ms responses (N100m) to vowels vs. tones suggested left
      hemispheric dominance in 8 of the 10 strongly right-handed subjects, and right
      hemispheric dominance in 7 of the 10 left-handed subjects. CONCLUSIONS: Our
      results demonstrate difference in hemispheric dominance for processing of vowels
      between right-handed and left-handed subjects. This difference resembles language
      lateralization suggested by previous invasive studies as well as by anatomical
      and functional comparisons in left- and right-handed subjects. SIGNIFICANCE:
      After comparison with the Wada test, this simple paradigm could prove useful as a
      noninvasive test for language lateralization in clinical settings.

PMID- 16403673
TI  - NC-stat sensory nerve conduction studies in the median and ulnar nerves of
      symptomatic patients.
AB  - OBJECTIVE: This study evaluated validity and reliability of automated median and
      ulnar sensory nerve conduction study (NCS) measurements by the NC-stat. METHODS:
      Median and ulnar distal sensory latencies (DSL) and amplitudes (SNAP) were
      measured in sixty subjects with the NC-stat and by a neurologist (reference)
      using traditional instrumentation. The median-ulnar DSL differences (MUD) was
      calculated. Validity was quantified by the Pearson correlation. Reliability was
      evaluated by the intraclass correlation coefficient (ICC), Bland-Altman analysis,
      and inter-rater agreement of MUD abnormalities. RESULTS: As a result of
      differences in electrode placement, NC-stat and reference mean values had
      systematic differences. The correlation ranged from 0.70 (ulnar DSL) to 0.91
      (median DSL). The ICC ranged from 0.69 (ulnar DSL) to 0.91 (median DSL). In Bland
      Altman analysis of DSLs, NC-stat measurements had a bias of 0.56 ms (median) and
      0.31 ms (ulnar) and precision of 0.31 and 0.30 ms. Inter-rater agreement for MUD
      abnormalities was 93.8% (raw) and 0.80 (Kappa). CONCLUSIONS: NC-stat validity and
      reliability metrics were similar to traditional NCS. Use of the NC-stat would
      require applicable reference ranges. SIGNIFICANCE: NC-stat median and ulnar NCS
      are valid and reliable. This device may be useful for increasing availability of
      NCS when clinically appropriate.

PMID- 16403674
TI  - Cervical nerve root stimulation. Part II: findings in primary demyelinating
      neuropathies and motor neuron disease.
AB  - OBJECTIVE: Cervical nerve root stimulation (CRS) allows the assessment of
      conduction in the proximal segments of motor fibers destined to the upper
      extremities, which are not evaluated by routine nerve conduction studies (NCS).
      Since many primary demyelinating polyneuropathies (PDP) are multifocal lesions
      may be confined to the proximal nerve segments. CRS may therefore increase the
      yield of neurophysiologic studies in diagnosing PDP. METHODS: We reviewed
      clinical and neurophysiologic data from 38 PDP patients and compared them to 35
      patients with motor neuron disease (MND), and 21 healthy controls (HC). RESULTS:
      Mean onset-latency was significantly prolonged in PDP patients. The optimal onset
      latency cutoff necessary to distinguish PDP from MND and controls was 17.5 ms for
      the abductor pollicis brevis (APB) and abductor digiti minimi (ADM), and 7 ms for
      Biceps and Triceps. Mean reduction in proximal to distal CMAP amplitude to APB
      and ADM was significantly greater in PDP patients, with an optimal cutoff in
      proximal to distal CMAP amplitude reduction necessary to distinguish PDP from MND
      and HC being 45%. CONCLUSIONS: CRS is effective in distinguishing PDP from MND
      and HC based on prolonged onset latency and conduction block criteria.
      SIGNIFICANCE: CRS may increase the diagnostic yield in cases where demyelinating
      lesions are confined to the proximal peripheral neuraxis.

PMID- 16403676
TI  - Lentiviral vectors for use in the central nervous system.
AB  - Lentiviral vectors have been used extensively as gene transfer tools for the
      central nervous system throughout the past decade since they transduce most cell
      types in the brain, resulting in high-level and long-term transgene expression.
      This review discusses some of the recent progress in this field, including
      preclinical gene therapy experiments in disease models, development of regulated
      vectors, and the application of siRNA's using lentiviral vectors. We also
      describe some of the features that make lentiviral vectors a likely candidate for
      human gene therapy in the brain.

PMID- 16403675
TI  - CD4+ T cell receptor repertoire perturbations in HIV-1 infection: association
      with plasma viremia and disease progression.
AB  - CD4+ T cell depletion and dysfunction are the hallmark of HIV-1 disease. Our
      primary objectives were to define the diversity of the CD4+ T cell receptor Vbeta
      (TCRBV) repertoire in subjects with HIV-1 infection by CDR3 (complementarity
      determining region) length spectratyping and to determine the correlates of CD4+
      repertoire perturbation and its restoration with virus suppression. During
      primary HIV-1 infection, the proportion of perturbed CD4+ TCRBV subfamilies was
      significantly greater compared to HIV-1 seronegative subjects (median 48% vs.
      10%, P = 0.0159). During chronic infection, the extent of repertoire perturbation
      was significantly associated with higher levels of plasma viremia (Spearman
      Correlation coefficient, R = 0.65, P = 0.049) and disease progression.
      Restoration of the repertoire with antiretroviral therapy was variable despite
      adequate virologic suppression. We speculate that the use of immunomodulators as
      an adjunct to antiretroviral drugs may enhance immune reconstitution in persons
      with suboptimal increases in CD4+ T cell counts despite adequate virus
      suppression.

PMID- 16403677
TI  - The key to ending stigma.

PMID- 16403678
TI  - Frequency of epileptiform EEG abnormalities in a sequential screening of autistic
      patients with no known clinical epilepsy from 1996 to 2005.
AB  - Autism spectrum disorders (ASDs) affect 1 in 166 births. Although
      electroencephalogram (EEG) abnormalities and clinical seizures may play a role in
      ASDs, the exact frequency of EEG abnormalities in an ASD population that has not
      had clinical seizures or prior abnormal EEGs is unknown. There is no current
      consensus on whether treatment of EEG abnormalities may influence development.
      This retrospective review of 24-hour ambulatory digital EEG data collected from
      889 ASD patients presenting between 1996 and 2005 (with no known genetic
      conditions, brain malformations, prior medications, or clinical seizures) shows
      that 540 of 889 (60.7%) subjects had abnormal EEG epileptiform activity in sleep
      with no difference based on clinical regression. The most frequent sites of
      epileptiform abnormalities were localized over the right temporal region. Of 176
      patients treated with valproic acid, 80 normalized on EEG and 30 more showed EEG
      improvement compared with the first EEG (average of 10.1 months to repeat EEG).

PMID- 16403679
TI  - Biochemical and functional aspects of crustacean hyperglycemic hormone in decapod
      crustaceans: review and update.
AB  - In crustaceans, neuroendocrine centers are located in different structures of the
      nervous system. One of these structures, the X-organ-sinus gland complex of the
      eyestalk, produces several neuropeptides that belong to the two main functionally
      different families: firstly, the chromatophorotropins, and secondly, a large
      family comprising various closely related peptides, commonly named CHH/MIH/GIH
      family. This review updates some aspects of the structural, biochemical and
      functional properties of the main hyperglycemic neuropeptide of this family, the
      crustacean hyperglycemic hormone (CHH). The first part of this work is a survey
      of the neuroendocrine system that produces the neurohormones of the CHH/MIH/GIH
      family, focusing on recent reports that propose new possible neuroendocrine loci
      of CHH production, secondly we revise general aspects of the CHH biochemical, and
      structural characteristics and thirdly, we present a review of the role of CHH in
      the regulation of several physiological processes of crustaceans as well as new
      reports on the ontogenetic aspects of CHH. The review is centered only on one
      group of malacostracan crustaceans, the Decapoda.

PMID- 16403681
TI  - Chemistry and reactions of reactive oxygen species in foods.
AB  - Reactive oxygen species (ROS) are formed enzymatically, chemically,
      photochemically, and by irradiation of food. They are also formed by the
      decomposition and the inter-reactions of ROS. Hydroxy radical is the most
      reactive ROS, followed by singlet oxygen. Reactions of ROS with food components
      produce undesirable volatile compounds and carcinogens, destroy essential
      nutrients, and change the functionalities of proteins, lipids, and carbohydrates.
      Lipid oxidation by ROS produces low molecular volatile aldehydes, alcohols, and
      hydrocarbons. ROS causes crosslink or cleavage of proteins and produces low
      molecular carbonyls from carbohydrates. Vitamins are easily oxidized by ROS,
      especially singlet oxygen. The singlet oxygen reaction rate was the highest in ss
      carotene, followed by tocopherol, riboflavin, vitamin D, and ascorbic acid.

PMID- 16403680
TI  - Anti-inflammatory influence of P-selectin on human mononuclear cells.
AB  - The purpose of this study was to determine if P-selectin, an adhesion molecule
      involved in the transendothelial movement of leukocytes, might also have a direct
      influence on the function of cells that come into contact with it. Human
      peripheral blood mononuclear cells were incubated on immobilized P-selectin or a
      control substrate (bovine serum albumin, BSA) and stimulated with bacterial
      lipopolysaccharide (LPS). After 24 h, the concentrations of proinflammatory
      cytokines in the supernatants of LPS-stimulated cells incubated on P-selectin
      were <50% of those produced by cells incubated on BSA (interleukin-1beta:
      P=0.001, tumor necrosis factor-alpha: P=0.004, and interferon-gamma : P=0.026).
      In contrast, cells incubated on P-selectin produced 74% more of the anti
      inflammatory cytokine interleukin-10 than cells incubated on BSA (P=0.013).
      Neither P-selectin nor BSA stimulated cytokine production in the absence of LPS.
      Thus, P-selectin modulated the cytokine secretion of peripheral blood mononuclear
      cells in a coordinated manner that reduced the inflammatory potential of the
      cells.

PMID- 16403682
TI  - Organic food: buying more safety or just peace of mind? A critical review of the
      literature.
AB  - Consumer concern over the quality and safety of conventional food has intensified
      in recent years, and primarily drives the increasing demand for organically grown
      food, which is perceived as healthier and safer. Relevant scientific evidence,
      however, is scarce, while anecdotal reports abound. Although there is an urgent
      need for information related to health benefits and/or hazards of food products
      of both origins, generalized conclusions remain tentative in the absence of
      adequate comparative data. Organic fruits and vegetables can be expected to
      contain fewer agrochemical residues than conventionally grown alternatives; yet,
      the significance of this difference is questionable, inasmuch as actual levels of
      contamination in both types of food are generally well below acceptable limits.
      Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate
      content compared with conventional ones, but whether or not dietary nitrate
      indeed constitutes a threat to human health is a matter of debate. On the other
      hand, no differences can be identified for environmental contaminants (e.g.
      cadmium and other heavy metals), which are likely to be present in food from both
      origins. With respect to other food hazards, such as endogenous plant toxins,
      biological pesticides and pathogenic microorganisms, available evidence is
      extremely limited preventing generalized statements. Also, results for mycotoxin
      contamination in cereal crops are variable and inconclusive; hence, no clear
      picture emerges. It is difficult, therefore, to weigh the risks, but what should
      be made clear is that 'organic' does not automatically equal 'safe.' Additional
      studies in this area of research are warranted. At our present state of
      knowledge, other factors rather than safety aspects seem to speak in favor of
      organic food.

PMID- 16403683
TI  - Composition, structure and absorption of milk lipids: a source of energy, fat
      soluble nutrients and bioactive molecules.
AB  - Milkfat is a remarkable source of energy, fat-soluble nutrients and bioactive
      lipids for mammals. The composition and content of lipids in milkfat vary widely
      among mammalian species. Milkfat is not only a source of bioactive lipid
      components, it also serves as an important delivery medium for nutrients,
      including the fat-soluble vitamins. Bioactive lipids in milk include
      triacylglycerides, diacylglycerides, saturated and polyunsaturated fatty acids,
      and phospholipids. Beneficial activities of milk lipids include anticancer,
      antimicrobial, anti-inflammatory, and immunosuppression properties. The major
      mammalian milk that is consumed by humans as a food commodity is that from bovine
      whose milkfat composition is distinct due to their diet and the presence of a
      rumen. As a result of these factors bovine milkfat is lower in polyunsaturated
      fatty acids and higher in saturated fatty acids than human milk, and the
      consequences of these differences are still being researched. The physical
      properties of bovine milkfat that result from its composition including its
      plasticity, make it a highly desirable commodity (butter) and food ingredient.
      Among the 12 major milk fatty acids, only three (lauric, myristic, and palmitic)
      have been associated with raising total cholesterol levels in plasma, but their
      individual effects are variable-both towards raising low-density lipoproteins and
      raising the level of beneficial high-density lipoproteins. The cholesterol
      modifying response of individuals to consuming saturated fats is also variable,
      and therefore the composition, functions and biological properties of milkfat
      will need to be re-evaluated as the food marketplace moves increasingly towards
      more personalized diets.

PMID- 16403684
TI  - Health implications of milk containing beta-casein with the A2 genetic variant.
AB  - Milk from dairy cows has long provided a high quality source of protein and
      selected micronutrients such as calcium to most populations. Recently, a
      relationship between disease risk and consumption of a specific bovine ss-casein
      fraction either A1 or A2 genetic variants has been identified. Populations, which
      consume milk containing high levels of ss-casein A2 variant, have a lower
      incidence of cardiovascular disease and type 1 diabetes. Furthermore, consumption
      of milk with the A2 variant may be associated with less severe symptoms of autism
      and schizophrenia. The mechanism of action focuses on ss-casein A1 and related
      forms preferentially that are able to produce a bioactive opioid peptide, ss
      casomorphin-7 (ss-CM-7) during digestion. Infants may absorb ss-CM-7 due to an
      immature gastrointestinal tract. Adults, on the other hand, appear to reap the
      biological activity locally on the intestinal brush boarder. ss-CM-7 can
      potentially affect numerous opioid receptors in the nervous, endocrine, and
      immune systems. Whether there is a definite health benefit to milk containing the
      A2 genetic variant is unknown and requires further investigation.

PMID- 16403685
TI  - ESH statement on detection and punishment of abstract fraud and poster
      plagiarism.

PMID- 16403686
TI  - Position of fixed-dose combinations containing an AT(1)-receptor blocker and a
      thiazide diuretic.
AB  - Treatment of hypertension remains a difficult task despite the availability of
      different types of medications lowering blood pressure by different mechanisms.
      In order to reach the target blood pressures recommended today combination
      therapy is required in most patients. The co-administration of two drugs with
      different impacts on the cardiovascular system markedly increases the
      antihypertensive effectiveness without altering adversely tolerability. Fixed low
      dose combinations are becoming a valuable option not only as second-line, but
      also as first-line therapy. In this respect the co-administration of thiazide
      diuretic with an AT(1)-receptor blocker is particularly appealing. The diuretic
      induced decrease in total body sodium activates the renin-angiotensin system,
      thus rendering blood pressure maintenance angiotensin II-dependent. During
      blockade of the renin-angiotensin system low doses of thiazides generally
      suffice, allowing the prevention of undesirable metabolic effects. Also, blockade
      of the AT(1)-receptor, particularly when angiotensin II production is enhanced in
      response to diuretic therapy, is expected to be beneficial, since angiotensin II
      seems to contribute importantly to the pathogenesis of cardiovascular and renal
      complications of hypertension.

PMID- 16403687
TI  - Swiss Hypertension and Risk Factor Program (SHARP): cardiovascular risk factors
      management in patients with type 2 diabetes in Switzerland.
AB  - The prevalence of hypertension in type 2 diabetics is high, though there is no
      published data for Switzerland. This prospective cohort survey determined the
      frequency of type 2 diabetes mellitus associated with hypertension from medical
      practitioners in Switzerland, and collected data on the diagnostic and
      therapeutic work-up for cardiovascular risk patients. The Swiss Hypertension And
      Risk Factor Program (SHARP) is a two-part survey: The first part, I-SHARP, was a
      survey among 1040 Swiss physicians to assess what are the target blood pressure
      (BP) values and preferred treatment for their patients. The second part, SHARP,
      collected data from 20,956 patients treated on any of 5 consecutive days from 188
      participating physicians. In I-SHARP, target BP?135/85 mmHg, as recommended by
      the Swiss Society of Hypertension, was the goal for 25% of physicians for
      hypertensives, and for 60% for hypertensive diabetics; values >140/90 mmHg were
      targeted by 19% for hypertensives, respectively 9% for hypertensive diabetics. In
      SHARP, 30% of the 20,956 patients enrolled were hypertensive (as defined by the
      doctors) and 10% were diabetic (67% of whom were also hypertensive). Six per cent
      of known hypertensive patients and 4% of known hypertensive diabetics did not
      receive any antihypertensive treatment. Diabetes was not treated
      pharmacologically in 20% of diabetics. Proteinuria was not screened for in 45% of
      known hypertensives and in 29% of known hypertensive diabetics. In Switzerland,
      most physicians set target BP levels higher than recommended in published
      guidelines. In this country with easy access to medical care, high medical
      density and few financial constraints, appropriate detection and treatment for
      cardiovascular risk factors remain highly problematic.

PMID- 16403688
TI  - Coronary flow reserve in dipper and non-dipper hypertensive patients.
AB  - BACKGROUND: Failure to decrease blood pressure (BP) normally during night-time,
      which is called non-dipping, in hypertensive individuals is associated with
      higher cardiovascular morbidity and mortality. In addition, non-dipping BP leads
      to structural changes in the left ventricle; however, the effect of non-dipping
      BP on coronary flow reserve (CFR) has not been studied yet. METHODS: In this
      study, we measured CFR of 22 subjects with non-dipper hypertension, and 15
      subjects with dipper hypertension using transthoracic second-harmonic Doppler
      echocardiography (Acuson Sequoia C256. None of the subjects had any systemic
      disease or coronary risk factor except hypertension. RESULTS: Age, gender, body
      mass index, lipids and echocardiographic findings including left ventricular mass
      index were similar between the groups. Office BP recordings were similar between
      non-dipper and dipper groups (147.9+/-6.1/93.9+/-4.3 vs 144.0+/-8.0/93.0+/-3.7).
      Daytime and 24-h ambulatory BP measurements were similar within the groups, but
      night-time BPs were significantly greater in non-dipper group than those were in
      dipper group. Left ventricular diastolic and systolic functions, and both
      baseline and hyperemic peak diastolic coronary velocity as well as CFR, were
      similar between the non-dipper and dipper groups (CFR: 2.47+/-0.59 vs 2.39+/
      0.47). CONCLUSION: CFR were similar in patients with non-dipper and dipper
      hypertension in the absence of excessive left ventricular hypertrophy and other
      cardiovascular risk factors.

PMID- 16403690
TI  - The effect of percutaneous dilatation of renal arterial stenosis on captopril
      renography in hypertension.
AB  - BACKGROUND: The clinical effects of percutaneous transluminal renal artery
      angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is
      controversial. METHODS: We consecutively recruited all 23 patients referred for
      evaluation of renovascular hypertension that eventually underwent unilateral
      PTRA, to be investigated with captopril MAG3 renography (CR), both before and
      after the endovascular procedure. Data were evaluated on an intention-to-treat
      basis. RESULTS: We found that the relative MAG3 clearance of the stenotic kidney
      increased (from 29.9+/-14% to 35.1+/-14%, p=0.01) and that the creatinine levels
      fell following the intervention (from 110+/-19 to 99+/-17 micromol/l, p=0.0003).
      Blood pressure levels were also lowered (from 173+/-32/93+/-17 to 158+/-31/86+/
      15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged
      following PTRA (2.9+/-1.4 before and 2.8+/-1.3 drugs after the intervention,
      respectively, p=0.6). CONCLUSION: This prospective trial showed statistically
      significant improvements of individual kidney function as measured by CR and
      blood pressure in subjects with suspected renovascular hypertension treated with
      PTRA. Although the endovascular procedure was found to be safe, the magnitude of
      the absolute improvements was rather modest.

PMID- 16403689
TI  - Blood pressure variability and white matter hyperintensities in older adults with
      cardiovascular disease.
AB  - The present study examined the relationship between multiple blood pressure (BP)
      indices and white matter hyperintensities (WMH) in a sample of 39 older adults
      with cardiovascular disease (CVD). Resting BP was measured using an automated
      monitor every 10 min for 2 h. WMH were quantified on FLAIR images and separate
      indices were generated for neocortical, periventricular and subcortical brain
      regions. Correlation analyses revealed systolic BP variability was related to
      neocortical and total WMH. A function of systolic BP variability and average
      diastolic pressure showed the strongest relationships, including significant
      correlation to neocortical, subcortical and total WMH. No BP index was related to
      WMH in periventricular regions. Exploratory analyses showed only the function of
      systolic BP variability and average diastolic pressure predicted total WMH,
      whereas as age, CVD conditions and psychosocial factors did not. These findings
      demonstrate BP variability is an important contributor to WMH in older adults
      with CVD and suggests it may have differential relationships to WMH in different
      brain regions. Additional studies are needed to examine the role of
      autoregulatory systems in the development of WMH, particularly those using beat
      to-beat measures of BP.

PMID- 16403691
TI  - Effect of glutathione peroxidase mimic ebselen (PZ51) on endothelium and vascular
      structure of stroke-prone spontaneously hypertensive rats.
AB  - BACKGROUND: To investigate whether extrinsic antioxidant seleno-glutathione
      peroxidase mimic ebselen (PZ51) can protect endothelium and vascular structure of
      stroke-prone spontaneously hypertensive rats (SHRsp) during the chronic process
      of hypertension. METHODS: Twenty-two 8-week-old SHRsp were randomized into a PZ51
      group and a control group, and administered by gavage for 6 weeks. We examined
      the level of nitric oxide (NO) and malonaldehyde (MDA) in plasma. The intima
      media thickness (IMT) of the common carotid artery (CCA) was measured by an image
      analysis system. The endothelium of the CCA was observed by scanning electron
      microscopy. The eNOS protein of the major artery was assayed by
      immunohistochemistry and western blotting. RESULTS: Compared with the control
      group, PZ51 decreased plasma MDA (7.88+/-1.06 vs 10.88+/-1.73 nmol/l, p<0.001)
      and increased plasma NO (40.02+/-9.74 vs 22.22+/-10.05 micromol/l, p<0.001),
      increased eNOS protein expression (8.25+/-2.36 vs 4.46+/-3.14, p=0.026),
      decreased IMT (69.85+/-5.47 vs 76.60+/-6.53 microm, p<0.05) significantly and
      alleviated the damage to the endothelium of the CCA. CONCLUSION: Administration
      of PZ51 for 6 weeks can protect the endothelium and inhibit vascular remodeling,
      maybe due to its suppression of lipid peroxide formation and increase in eNOS
      protein expression.

PMID- 16403692
TI  - High sodium intake increases vascular superoxide formation and promotes
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - Hypertension is a major risk factor for atherosclerosis. We tested the hypothesis
      whether high salt intake aggravates endothelial dysfunction and promotes
      atherosclerosis in apolipoprotein E-deficient mice (ApoE(-)/(-) mice) and their
      littermate controls (C57Bl/6 mice). The role of increased oxidative stress was
      also examined. A high-salt diet (NaCl 7%) for 12 weeks increased blood pressure
      and induced cardiac hypertrophy and albuminuria more pronouncedly in ApoE(-)/(-)
      mice compared with C57Bl/6. Endothelium-dependent vascular relaxation in response
      to acetylcholine was almost maximally impaired in ApoE(-)/(-) mice during a
      normal sodium diet. A high-salt diet did not further impair NO-mediated vascular
      relaxation. A high-salt diet also markedly attenuated endothelium-dependent
      relaxation in C57Bl/6 mice. Preincubation with the superoxide scavenger Tiron
      normalized endothelial function almost completely in both mice strains indicating
      the central role of increased oxidative stress in the pathogenesis. Aortic
      superoxide production and the extent of atherosclerotic lesions were greater in
      ApoE(-)/(-) mice on a normal-salt diet compared with C57Bl/6. The high-salt diet
      increased vascular superoxide formation and promoted atherosclerosis in ApoE(-)/(
      ) mice. Changes in dietary salt intake did not influence serum lipids in either
      mouse strains. Our findings suggest a detrimental role for high salt intake in
      the development of atherosclerosis and underscore the importance of increased
      oxidative stress in the pathogenesis salt-induced vascular damage.

PMID- 16403693
TI  - Association of periodontitis with blood pressure.

PMID- 16403695
TI  - Who benefits? Outcome following a coping skills group intervention for
      traumatically brain injured individuals.
AB  - PRIMARY OBJECTIVE: To investigate the variables associated with positive
      psychological outcome following a group intervention for 33 individuals with
      traumatic brain injury. RESEARCH DESIGN: Evaluation study which used multiple
      regression analysis to examine the variables associated with change in
      psychological adjustment following a 10-session cognitive behaviour therapy-based
      group. METHODS AND PROCEDURES: The predictor variables were age at injury, time
      since injury, injury severity, self-awareness, pre-morbid intellectual function,
      memory function, executive function and level of depression and anxiety prior to
      intervention. MAIN OUTCOMES AND RESULTS: The predictor variables contributed a
      significant proportion of the variance in percentage change in depression. The
      major finding was that better outcomes following intervention were associated
      with greater self-awareness of injury-related deficits. CONCLUSIONS: The present
      study identified a number of variables that were associated with improvement in
      depression following psychological intervention and may assist future treatment
      resources to be directed most effectively.

PMID- 16403696
TI  - Clinical significance of dilated Virchow-Robin spaces in mild traumatic brain
      injury.
AB  - PRIMARY OBJECTIVE: To investigate the relationship between the number of dilated
      Virchow-Robin spaces (VRS) and neurocognitive findings in patients with traumatic
      brain injury (TBI). RESEARCH DESIGN: Thirty-eight patients with TBI and 21
      controls were studied. METHODS AND PROCEDURES: Fifteen patients underwent MRI
      within a mean interval of 5.4 (range 1-12) days from the brain injury and 23
      after an average period of 5.5 (range 0.2-31) years. All subjects were examined
      with a battery of 13 neuropsychological tests (NP). MAIN OUTCOMES AND RESULTS:
      The average number of VRS was significantly higher in patients than in controls.
      There were no significant differences between patients and controls in terms of
      NP tests. The number of VRS showed a significant inverse correlation with
      processing speed and a positive correlation with visual perceptual of attention
      only in patients studied within a short delay of trauma. CONCLUSIONS: VRS are not
      directly associated to neurocognitive findings, suggesting that they may
      represent a result of the shear-strain injury.

PMID- 16403697
TI  - Central executive system impairment in traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This study investigated whether cognitive impairment after
      traumatic brain injury (TBI) can be considered a consequence of (1) a speed
      processing deficit or (2) an impairment of the Central Executive System (CES) of
      working memory. METHODS AND PROCEDURES: Thirty-seven TBI patients underwent a
      standardized battery of neuropsychological tests evaluating speed processing,
      sustained attention, short-term memory, working memory, divided attention,
      executive functions and long-term memory. MAIN OUTCOMES AND RESULTS: Patients
      showed severe deficits in working memory, divided attention, executive functions
      and long-term memory. Divided attention, long-term memory and executive functions
      deficits significantly correlated with working memory, but not with speed
      processing deficits. Moreover, multiple regression analyses showed that a CES
      impairment and not a speed processing deficit predicted divided attention,
      executive functions and long-term memory deficits. The severity and the site of
      brain lesions did not predict the level of CES or speed processing impairment.
      CONCLUSIONS: The cognitive impairment following TBI seem to be caused by an
      impairment of the Central Executive System, rather than a speed processing
      deficit.

PMID- 16403698
TI  - Recovery from sports concussion in high school and collegiate athletes.
AB  - INTRODUCTION: Neuropsychological testing is a valuable tool in concussion
      diagnosis and management. ImPACT, a computerized neuropsychological testing
      program, consists of eight cognitive tasks and a 21-item symptom inventory.
      METHOD: ImPACT was used to examine the cognitive performance of 104 concussed
      athletes at baseline, 2, 7 and 14 days post-injury. Dependent measures included
      composite scores from the ImPACT computerized test battery, as well as a total
      symptom score from the Post-Concussion Symptom Scale. RESULTS: Differences
      between baseline and day 2 post-injury scores were observed for all ImPACT
      composites (Verbal memory-VERM, visual memory-VISM, processing speed-PROC and
      reaction time-RT) as well as in total symptom score (SX). At day 7, concussed
      athletes continued to perform significantly poorer on VERM, VISM, RT and SX. At
      day 14, only VERM scores were significantly different from baseline. CONCLUSIONS:
      Cognitive performance deficits in concussed athletes may persist to 7 and even to
      14 days in some cases. In addition to symptom status, the athlete's post
      concussion cognitive functioning should be considered when making return-to-play
      decisions.

PMID- 16403699
TI  - Co-morbid traumatic brain injury and substance use disorder: childhood predictors
      and adult correlates.
AB  - PRIMARY OBJECTIVE: To examine demographic factors, childhood experiences and
      behaviour problems and adult psychopathology associated with a history of adult
      traumatic brain injury (TBI) with unconsciousness in patients with substance use
      disorders (SUD). DESIGN AND METHODS: Voluntary patients (n = 550) undergoing
      treatment for SUD were compared for clinical and demographic variables based on
      report of TBI. RESULTS: Among the 218 (40%) patients reporting TBI, 61% were men.
      Childhood conduct problems and loss of a parent were strongly associated with
      adult TBI. Patients with TBI had more severe SUD and higher rates of depressive
      and anxiety symptoms, somatic concerns, physical trauma, attempted suicide and
      Antisocial Personality Disorder. CONCLUSIONS: Men have a higher rate of TBI than
      women, but women with SUD have an increased relative risk of TBI compared to
      women in the general population. Childhood conduct problems and loss of a parent
      in childhood may predict adult risk-taking behaviour that leads to TBI in
      patients with SUD. TBI is associated with higher rates of psychopathology in
      patients with SUD.

PMID- 16403700
TI  - Increased inattentional blindness in severe traumatic brain injury: evidence for
      reduced distractibility?
AB  - PRIMARY OBJECTIVE: To examine the role of selective attention and visual
      perception in medicating inattentional blindness in a severe traumatic brain
      injured sample. RESEARCH DESIGN: Cross-sectional design with age and education
      matched control sample. METHODS AND PROCEDURES: Twenty participants with severe
      traumatic brain injury (n = 10) and matched controls (n = 10) completed a series
      of tests of focused attention (Stroop test), divided attention (Trail Making
      Test), visual perception (Visual Object and Space Perception Battery) and two
      tasks of inattentional blindness. MAIN OUTCOMES AND RESULTS: The group with
      severe TBI were significantly slower on the Stroop test and TMT and displayed
      significantly elevated Stroop interference and TMT ratio scores. On the
      inattentional blindness tasks, fewer TBI participants identified a distracting
      stimulus. CONCLUSION: The results indicate severe TBI is associated with deficits
      to focused and divided attention with the finding of a potentially more
      debilitating impairment arising from reduced distractibility following severe
      TBI.

PMID- 16403701
TI  - Executive dysfunction and domestic violence.
AB  - PRIMARY OBJECTIVE: To replicate previous studies which have reported a high
      prevalence of traumatic brain injury (TBI) in partner-abusive men and to extend
      research in this area by determining the prevalence of executive dysfunctions,
      which have been linked with both TBI and violent behaviour. RESEARCH DESIGN:
      Thirty-eight men with criminal convictions for violence and who were receiving
      treatment for abusing their partners were assessed. METHODS AND PROCEDURES:
      Subjects with a self-reported history of TBI (n = 22) were compared to the non
      TBI group (n = 16) on various psychological measures. MAIN OUTCOMES AND RESULTS:
      The two groups were not significantly different on the variables of age, pre
      morbid IQ, self-esteem and alcohol use. The TBI group scored more poorly than the
      non-TBI group on a measure of current IQ and two of the three measures of
      executive functioning. CONCLUSION: The presence of executive dysfunction has
      implications for the design of successful intervention programmes with this sub
      group of batterers.

PMID- 16403703
TI  - What about theory of mind after severe brain injury?
AB  - BACKGROUND: Behavioural changes are often reported after a severe traumatic brain
      injury (TBI). These changes are usually a greater burden for relatives than
      physical or cognitive impairments. This study investigated social cognition in
      TBI patients using two theory of mind (TOM) tasks. METHOD: The performances of 17
      patients with severe TBI and 17 matched controls were compared on two tasks
      designed to investigate understanding of other people's mental states: The
      'Reading the Mind in the Eyes' test (RME) and the 'Character Intention Task'
      (CIT). TBI patients and controls were also given several executive function
      tasks. RESULTS: Compared to healthy controls, patients were impaired in most
      executive tests and in both TOM tasks. No relationship was found between TOM and
      executive measures. This is consistent with Rowe's position, who suggested an
      independence between executive functioning and social cognition. These data
      suggest that TBI patients may have specific social intelligence disturbances.
      CONCLUSION: Future work should employ additional tests of TOM and behavioural
      ratings and recruit more patients in order to complete analysis.

PMID- 16403702
TI  - Inhibition and object relations in borderline personality traits after traumatic
      brain injury.
AB  - This study aims to assess the nature and severity of borderline traits after
      traumatic brain injury (TBI). Thirty subjects with moderate or severe TBI were
      compared to 30 normal controls on the Revised Diagnostic Interview for
      Borderlines (DIB-R), a dimensional measure of borderline traits, the Go-no go
      inhibition task, the Complexity of Representations of People and Affect-Tone
      Relationships Paradigms, two scales from the Social Cognition and Object
      Relations Scale (SCORS) evaluating the quality of object relations, an estimation
      of pre-morbid borderline severity, the Beck Depression Inventory (BDI) and
      various neuropsychological measures. Results indicate that TBIs present more
      borderline symptoms and traits than controls. However, the severity of borderline
      symptomatology remains comparatively low for the vast majority. As expected, the
      TBI group showed a poorer performance on the Go-no go task, a characteristic
      neuropsychological inhibition deficit. Yet, both samples present similar profiles
      on the SCORS. Finally, the DIB-R was correlated with the Affect-Tone scale, the
      BDI and with the pre-morbid severity estimation. Results suggest that post-TBI
      borderline traits remain rare and relate more to the affective quality of object
      relations, negative affects and pre-morbid borderline pathology than inhibition
      deficits.

PMID- 16403704
TI  - Errors in self-report of post-traumatic stress disorder after severe traumatic
      brain injury.
AB  - Assessing PTSD by questionnaire can lead to false positive diagnosis after severe
      traumatic brain injury. Sumpter and McMillan, reported quantitative data on 34
      people with severe TBI; 59% were PTSD 'cases' by questionnaire assessment, but
      only 3% using a structured interview. The present paper describes ways in which
      these individuals made errors on questionnaires. Some did not follow
      questionnaire instructions because of inattention and concrete thinking or
      instead reported effects of brain injury. Symptom overlap between TBI and PTSD,
      including insomnia, irritability and impaired concentration can cause errors.
      Brain injury can also provoke curiosity about loss of memory (during coma,
      retrograde and post-traumatic amnesia), decreased participation, social
      withdrawal and difficulty adjusting to injury that may be mistaken for fear
      associated PTSD symptoms. Assessment of PTSD by questionnaire can lead to
      erroneous conclusions and factors related to brain injury must be carefully
      considered when investigating PTSD.

PMID- 16403705
TI  - Improvement patterns among survivors of brain injury: three case examples
      documenting the effectiveness of memory compensation strategies.
AB  - Three case examples illustrate possible patterns of improved functioning that may
      emerge as survivors of traumatic brain injury (TBI) attempt compensation for
      persistent memory deficits impeding independent living. The task selected for
      report was independence in remembering to take regularly-prescribed medications.
      Strategies applied to promote learning included use of written reminders and use
      of two assistive technology (AT) devices-a wristwatch alarm (WatchMinder) and a
      digital voice recorder and alarm system (Voice Craft ). With participation in the
      intervention programme, two of the three individuals demonstrated increased
      independence in remembering to take medications; the third did not. The case
      examples illustrate varying responses of people with TBI to intervention using
      compensatory strategies and AT devices. Professionals and caretakers working with
      survivors must recognize the uniqueness of each survivor, must adjust
      intervention programmes accordingly and must be willing to persist in trying to
      increase functional independence repeatedly for many years post-injury.

PMID- 16403706
TI  - Bromocriptine in traumatic brain injury.
AB  - The authors report the case of a 63-year-old patient with severe traumatic brain
      injury (TBI) associated with Parkinson's syndrome, whose performances were
      dramatically improved by bromocriptine therapy, with an improvement of the
      scores, not only on tests evaluating motor functions but also on tests evaluating
      the patient's cognitive functions. However, no improvement was observed with
      levodopa.

PMID- 16403707
TI  - An image-analysis system based on support vector machines for automatic grade
      diagnosis of brain-tumour astrocytomas in clinical routine.
AB  - An image-analysis system based on the concept of Support Vector Machines (SVM)
      was developed to assist in grade diagnosis of brain tumour astrocytomas in
      clinical routine. One hundred and forty biopsies of astrocytomas were
      characterized according to the WHO system as grade II, III and IV. Images from
      biopsies were digitized, and cell nuclei regions were automatically detected by
      encoding texture variations in a set of wavelet, autocorrelation and parzen
      estimated descriptors and using an unsupervised SVM clustering methodology. Based
      on morphological and textural nuclear features, a decision-tree classification
      scheme distinguished between different grades of tumours employing an SVM
      classifier. The system was validated for clinical material collected from two
      different hospitals. On average, the SVM clustering algorithm correctly
      identified and accurately delineated 95% of all nuclei. Low-grade tumours were
      distinguished from high-grade tumours with an accuracy of 90.2% and grade III
      from grade IV with an accuracy of 88.3% The system was tested in a new clinical
      data set, and the classification rates were 87.5 and 83.8%, respectively.
      Segmentation and classification results are very encouraging, considering that
      the method was developed based on every-day clinical standards. The proposed
      methodology might be used in parallel with conventional grading to support the
      regular diagnostic procedure and reduce subjectivity in astrocytomas grading.

PMID- 16403708
TI  - Completeness and accuracy of WWW-based catalogues of medical E-learning modules.
AB  - Catalogues of medical E-learning modules offer easy access to learning material
      that is available on the World Wide Web (WWW) free of charge. Therefore, a study
      was conducted on the retrieval performance of four WWW-based catalogues: CAL
      reviews, KELDAmed, LMU, and LRSMed. LRSMed is run by the authors. Completeness
      was calculated pairwise. Two reviewers checked the availability of 80 modules
      independently. Five criteria were chosen to calculate accuracy: gynaecology and
      microbiology as medical fields; case study as type of learning resource; diabetes
      mellitus and AIDS as free-text diagnoses. Also, two reviewers evaluated
      independently whether the module is really an appropriate resource for that
      criterion or not. The analysis is based on a consensual decision about the
      correct votes. From the URLs, 93% were available at the evaluation of
      completeness, 92% at the evaluation of accuracy. The kappa values for inter-rater
      reliability were 0.83 and 0.36. The best service offers 60.8% of the pooled E
      learning resources. The resources retrieved by the five criteria were rated as
      correct in 69.3% (LRSMed), 76.6% (KELDAmed), and 82.7% (CAL reviews). The overall
      accuracy was 76.7%. Medical students and other potential users of E-learning
      modules should be aware that the completeness of WWW-based catalogues in this
      area is not satisfying. The retrieval accuracy is better; four of five resources
      offered correspond with the search criterion. Up to now, most of the services
      miss an application-programming interface that could be used for a meta-search to
      improve completeness.

PMID- 16403709
TI  - A systematic approach to medical decision-making of uncommon clinical pictures: a
      case of ulcerative skin lesions by palm tree thorn injury and a one-year follow
      up.
AB  - In clinical practice, the clinician is challenged with symptoms and/or signs at
      times apparently insoluble by diagnostic and/or therapeutic means. We propose
      that in these cases, we have to use an EBM approach in which evidence may be
      looked up in every available clinical report and bibliographic databases are used
      for searching that evidence. We report on a case of ulcerative skin lesions
      apparently insoluble by expert dermatologists following a conventional diagnostic
      and therapeutic process. We use this case report for illustrating a systematic
      approach to resolve diagnostic and therapeutic questions using a bibliographic
      database search (like MEDLINE and EMBASE). Both a systematic approach to
      bibliographic databases and a critically appraised topic on case reports (or case
      series) are needed to 'rehabilitate' low-level evidences (that is a case report
      or case series) to a higher level when we approach decision-making of uncommon
      clinical pictures. We demonstrate the possibility of using bibliographic
      databases to search and retrieve useful information for decision-making of
      uncommon clinical pictures. The method we have proposed can be applied in every
      area of the world, especially in rural areas. Finally, an Internet-shared
      database of uncommon clinical pictures with critically appraised topics could be
      useful in saving more time.

PMID- 16403710
TI  - A novel approach for incremental uncertainty rule generation from databases with
      missing values handling: application to dynamic medical databases.
AB  - Current approaches for mining association rules usually assume that the mining is
      performed in a static database, where the problem of missing attribute values
      does not practically exist. However, these assumptions are not preserved in some
      medical databases, like in a home care system. In this paper, a novel uncertainty
      rule algorithm is illustrated, namely URG-2 (Uncertainty Rule Generator), which
      addresses the problem of mining dynamic databases containing missing values. This
      algorithm requires only one pass from the initial dataset in order to generate
      the item set, while new metrics corresponding to the notion of Support and
      Confidence are used. URG-2 was evaluated over two medical databases, introducing
      randomly multiple missing values for each record's attribute (rate: 5-20% by 5%
      increments) in the initial dataset. Compared with the classical approach (records
      with missing values are ignored), the proposed algorithm was more robust in
      mining rules from datasets containing missing values. In all cases, the
      difference in preserving the initial rules ranged between 30% and 60% in favour
      of URG-2. Moreover, due to its incremental nature, URG-2 saved over 90% of the
      time required for thorough re-mining. Thus, the proposed algorithm can offer a
      preferable solution for mining in dynamic relational databases.

PMID- 16403711
TI  - A patient-identity security mechanism for electronic medical records during
      transit and at rest.
AB  - This paper proposes a patient-identity security mechanism, including an identity
      cipher/decipher and a user-authentication protocol, to ensure the confidentiality
      and authentication of patients' electronic medical records (EMRs) during transit
      and at rest. To support the confidentiality of an EMR, the identity
      cipher/decipher uses a data-hiding function and three logical-based functions to
      encrypt/decrypt a patient's identifying data and medical details in an EMR. The
      ciphertext of the patient's identifying data is patient-EMR related, whereas that
      of medical details is healthcare agent-EMR related. To support the authentication
      of an EMR, the user-authentication protocol based on a public key infrastructure
      uses certificates and dynamic cookies for verification/identification. The
      identity cipher has been simulated using C programming language running on a 1500
      MHz Pentium PC with 512 MB of RAM. The experimental results show that healthcare
      agents can install large amounts of patients' encrypted EMRs in healthcare
      databases efficiently. In addition, separately storing the keys in a user's token
      and an EMR database for decryption increases the safety of patients' EMRs. For
      each user-authentication trail, the use of certificates and dynamic cookies for
      verification/identification ensures that only authorized users can obtain access
      to the EMR, and anyone involved cannot make false claims on the transmission
      made.

PMID- 16403712
TI  - The use of minimized extracorporeal circulation system has a beneficial effect on
      hemostasis--a randomized clinical study.
AB  - BACKGROUND: Conventional cardiopulmonary bypass (CPB) is associated with
      increased coagulation and fibrinolytic activity. A closed miniaturized bypass
      circuit (CorX) features a significantly reduced tubing set, an integrated pump,
      and an air removal system without a cardiotomy reservoir. In a prospective
      randomized trial, the effects on hemostasis were investigated while comparing
      CorX with conventional CPB in patients undergoing coronary artery bypass
      grafting. METHODS: Over a period of 1 year, 81 patients were randomly assigned
      either to the CorX system (n = 39, group A) or standard CPB system (n = 42, group
      B). Primary endpoints were platelet count, plasmin-antiplasmin complex (PAP),
      prothrombin fragments 1+2 (F1+F2), D-dimers, and fibrinogen. Secondary end-points
      were hematocrit, blood loss in the first 12 hours postoperatively, transfused
      packed red blood cells, and fresh frozen plasma in the first 24 hours
      postoperatively. In addition, we analyzed partial thromboplastin time,
      prothrombin time, and antithrombin III. RESULTS: After aortic declamping, PAP
      complex and prothrombin F1+F2 were significantly lower in group A than in group
      B. The difference in D-dimers between groups reached significance at 1 hour post
      CPB. Hematocrit values at the end of CPB measured 26 +/- 6% in group A versus 22
      +/- 4% in group B (P = .01). The rest of the observed parameters did not
      significantly differ between groups. CONCLUSION: Postoperative blood loss was not
      reduced in the present study. However, the use of the CorX system leads to a
      significant suppression of activation of coagulation and fibrinolytic cascades
      compared to conventional CPB, suggesting that miniaturized extracorporeal
      circuits are a step forward toward reduced imbalance of hemostasis in cardiac
      surgery.

PMID- 16403713
TI  - Erdheim-Chester's disease of the heart: a diagnostic conundrum and collision with
      the same mass in the orbit.
AB  - Erdheim-Chester's disease is a rare multisystem xanthogranulomatosis, afflicting
      the skeletal system with the occasional involvement of soft tissues. We delineate
      an unusual case of a cardiac variant of Erdheim-Chester's disease presenting with
      pericardial effusion and as a collision with a synchronous orbital manifestation.
      We describe our diagnostic pathway and propose a novel treatment option involving
      nonsteroidal anti-inflammatory drugs. The role of cyclo-oxygenase in the disease
      process and inhibition thereof by NSAIDs is hypothesized and discussed.

PMID- 16403714
TI  - A historical overview of health disparities and the potential of eHealth
      solutions.
AB  - Over the past decade, a rapidly expanding body of literature has demonstrated the
      existence of disparities in health and health care. While consensus has not
      emerged regarding the causes of disparities, they are generally thought to be
      related to sociocultural, behavioral, economic, environmental, biologic, or
      societal factors. To effectively address disparities, several authorities have
      suggested the need for greater information technology research and investments.
      eHealth researchers may be able to make significant contributions in this area
      through research and its applications. This paper begins with a historical
      overview of health disparities in the United States and Europe. It then discusses
      the role that the Internet, and access to the Internet, may play in the genesis
      of health disparities. Finally, this paper closes with a discussion of the
      potential benefits of eHealth applications and the possible contributions of the
      field to overcoming disparities in health and health care.

PMID- 16403715
TI  - Computers and the internet: tools for youth empowerment.
AB  - BACKGROUND: Youth are often disenfranchised in their communities and may feel
      they have little voice. Since computers are an important aspect of youth culture,
      they may offer solutions to increasing youth participation in communities.
      OBJECTIVE: This qualitative case study investigated the perceptions of 19
      (predominantly female) inner-city school youth about their use of computers and
      the Internet in a school-based community development project. METHODS: Youth
      working with public health nurses in a school-based community development project
      communicated with local community members using computer-mediated communication,
      surveyed peers online, built websites, searched for information online, and
      prepared project materials using computers and the Internet. Participant
      observation, semistructured interviews, analysis of online messages, and online-
      and paper-based surveys were used to gather data about youth's and adults'
      perceptions and use of the technologies. Constant comparison method and between
      method triangulation were used in the analysis to satisfy the existence of
      themes. RESULTS: Not all youth were interested in working with computers. Some
      electronic messages from adults were perceived to be critical, and writing to
      adults was intimidating for some youth. In addition, technical problems were
      experienced. Despite these barriers, most youth perceived that using computers
      and the Internet reduced their anxiety concerning communication with adults,
      increased their control when dealing with adults, raised their perception of
      their social status, increased participation within the community, supported
      reflective thought, increased efficiency, and improved their access to resources.
      CONCLUSIONS: Overall, youth perceived computers and the Internet to be empowering
      tools, and they should be encouraged to use such technology to support them in
      community initiatives.

PMID- 16403716
TI  - Architecture for knowledge-based and federated search of online clinical
      evidence.
AB  - BACKGROUND: It is increasingly difficult for clinicians to keep up-to-date with
      the rapidly growing biomedical literature. Online evidence retrieval methods are
      now seen as a core tool to support evidence-based health practice. However,
      standard search engine technology is not designed to manage the many different
      types of evidence sources that are available or to handle the very different
      information needs of various clinical groups, who often work in widely different
      settings. OBJECTIVES: The objectives of this paper are (1) to describe the design
      considerations and system architecture of a wrapper-mediator approach to federate
      search system design, including the use of knowledge-based, meta-search filters,
      and (2) to analyze the implications of system design choices on performance
      measurements. METHODS: A trial was performed to evaluate the technical
      performance of a federated evidence retrieval system, which provided access to
      eight distinct online resources, including e-journals, PubMed, and electronic
      guidelines. The Quick Clinical system architecture utilized a universal query
      language to reformulate queries internally and utilized meta-search filters to
      optimize search strategies across resources. We recruited 227 family physicians
      from across Australia who used the system to retrieve evidence in a routine
      clinical setting over a 4-week period. The total search time for a query was
      recorded, along with the duration of individual queries sent to different online
      resources. RESULTS: Clinicians performed 1662 searches over the trial. The
      average search duration was 4.9 +/- 3.2 s (N = 1662 searches). Mean search
      duration to the individual sources was between 0.05 s and 4.55 s. Average system
      time (ie, system overhead) was 0.12 s. CONCLUSIONS: The relatively small system
      overhead compared to the average time it takes to perform a search for an
      individual source shows that the system achieves a good trade-off between
      performance and reliability. Furthermore, despite the additional effort required
      to incorporate the capabilities of each individual source (to improve the quality
      of search results), system maintenance requires only a small additional overhead.

PMID- 16403717
TI  - Comparative case study of two biomedical research collaboratories.
AB  - BACKGROUND: Working together efficiently and effectively presents a significant
      challenge in large-scale, complex, interdisciplinary research projects.
      Collaboratories are a nascent method to help meet this challenge. However, formal
      collaboratories in biomedical research centers are the exception rather than the
      rule. OBJECTIVE: The main purpose of this paper is to compare and describe two
      collaboratories that used off-the-shelf tools and relatively modest resources to
      support the scientific activity of two biomedical research centers. The two
      centers were the Great Lakes Regional Center for AIDS Research (HIV/AIDS Center)
      and the New York University Oral Cancer Research for Adolescent and Adult Health
      Promotion Center (Oral Cancer Center). METHODS: In each collaboratory, we used
      semistructured interviews, surveys, and contextual inquiry to assess user needs
      and define the technology requirements. We evaluated and selected commercial
      software applications by comparing their feature sets with requirements and then
      pilot-testing the applications. Local and remote support staff cooperated in the
      implementation and end user training for the collaborative tools. Collaboratory
      staff evaluated each implementation by analyzing utilization data, administering
      user surveys, and functioning as participant observers. RESULTS: The HIV/AIDS
      Center primarily required real-time interaction for developing projects and
      attracting new participants to the center; the Oral Cancer Center, on the other
      hand, mainly needed tools to support distributed and asynchronous work in small
      research groups. The HIV/AIDS Center's collaboratory included a center-wide
      website that also served as the launch point for collaboratory applications, such
      as NetMeeting, Timbuktu Conference, PlaceWare Auditorium, and iVisit. The
      collaboratory of the Oral Cancer Center used Groove and Genesys Web conferencing.
      The HIV/AIDS Center was successful in attracting new scientists to HIV/AIDS
      research, and members used the collaboratory for developing and implementing new
      research studies. The Oral Cancer Center successfully supported highly
      distributed and asynchronous research, and the collaboratory facilitated real
      time interaction for analyzing data and preparing publications. CONCLUSIONS: The
      two collaboratory implementations demonstrated the feasibility of supporting
      biomedical research centers using off-the-shelf commercial tools, but they also
      identified several barriers to successful collaboration. These barriers included
      computing platform incompatibilities, network infrastructure complexity, variable
      availability of local versus remote IT support, low computer and collaborative
      software literacy, and insufficient maturity of available collaborative software.
      Factors enabling collaboratory use included collaboration incentives through
      funding mechanism, a collaborative versus competitive relationship of
      researchers, leadership by example, and tools well matched to tasks and technical
      progress. Integrating electronic collaborative tools into routine scientific
      practice can be successful but requires further research on the technical,
      social, and behavioral factors influencing the adoption and use of
      collaboratories.

PMID- 16403718
TI  - What is eHealth (5): a research agenda for eHealth through stakeholder
      consultation and policy context review.
AB  - BACKGROUND: In 2003, the National Health Service in England and Wales, despite
      its large investment in information and communication technology, had not set a
      national research agenda. The National Health Service has three main research and
      development programs: one is the Service Delivery and Organisation program,
      commissioned in 2003, and the others are two parallel "scoping exercises" to help
      set a research agenda. This paper reports on one of those projects. A parallel
      literature review was carried out by others and has been reported elsewhere.
      OBJECTIVE: The objective was to explore the concerns of stakeholders and to
      review relevant policy in order to produce recommendations and a conceptual map
      of eHealth research. METHODS: There were two parallel strands. For the
      stakeholder consultation, 37 professionals representing 12 "stakeholder" groups
      participated in focus groups or interviews. Discussion was prompted by eHealth
      "scenarios" and analyzed using thematic content analysis. Subsequently, 17 lay
      participants, in three focus groups, discussed and prioritized these themes. For
      the policy review, 26 policy makers were interviewed, and 95 policy documents
      were reviewed. Recommendations were subsequently reviewed in a conference
      workshop. Recommendations for research from both strands were combined into a
      conceptual map. RESULTS: Themes from stakeholder consultation and policy review
      were combined as 43 recommendations under six headings. Four of these headings
      (using, processing, sharing, and controlling information) describe the scope of
      eHealth research. The other two relate to how research should be carried out
      (ensuring best practice is first identified and disseminated) and to the values
      considered important by stakeholders (in particular, measuring improvement in
      health). CONCLUSIONS: The scope of eHealth research (using, processing, sharing,
      controlling information) derived empirically from this study corresponds with
      "textbook" descriptions of informatics. Stakeholders would like eHealth research
      to include outcomes such as improved health or quality of life, but such research
      may be long term while changes in information technology are rapid. Longer-term
      research questions need to be concerned with human behavior and our use of
      information, rather than particular technologies. In some cases, "modelling"
      longer-term costs and benefits (in terms of health) may be desirable.

PMID- 16403719
TI  - Website quality indicators for consumers.
AB  - BACKGROUND: The rating tool DISCERN was designed for use by consumers without
      content expertise to evaluate the quality of health information. There is some
      evidence that DISCERN may be a valid indicator of evidence-based website quality
      when applied by health professionals. However, it is not known if the tool is a
      valid measure of evidence-based quality when used by consumers. Since it is a
      lengthy instrument requiring training in its use, DISCERN may prove impractical
      for use by the typical consumer. It is therefore important to explore the
      validity of other simpler potential indicators of site quality such as Google
      PageRank. OBJECTIVE: This study aimed to determine (1) whether the instrument
      DISCERN is a valid indicator of evidence-based Web content quality for consumers
      without specific mental health training, and (2) whether Google PageRank is an
      indicator of website content quality as measured by an evidence-based gold
      standard. METHODS: This was a cross-sectional survey of depression websites using
      consumer and health professional raters. The main outcome measures were (1) site
      characteristics, (2) evidence-based quality of content as measured by evidence
      based depression guidelines, (3) DISCERN scores, (4) Google PageRank, and (5)
      user satisfaction. RESULTS: There was a significant association between evidence
      based quality ratings and average DISCERN ratings both for consumers (r = 0.62, P
      = .001) and health professionals (r = 0.80, P < .001). Consumer and health
      professional DISCERN ratings were significantly correlated (r = 0.77, P < .001).
      The evidence-based quality score correlated with Google PageRank (r = 0.59, P =
      .002). However, the correlation between DISCERN scores and user satisfaction was
      higher than the correlation between Google PageRank and user satisfaction.
      CONCLUSIONS: DISCERN has potential as an indicator of content quality when used
      either by experts or by consumers. Google PageRank shows some promise as an
      automatic indicator of quality.

PMID- 16403720
TI  - Feasibility of adding enhanced pedometer feedback to nutritional counseling for
      weight loss.
AB  - BACKGROUND: Intensive interventions targeting diet and physical activity are
      effective for weight reduction but are costly. Tailored, computer-generated, step
      count feedback may provide an intensive and affordable way to increase the
      physical activity of people at high risk for cardiovascular disease. OBJECTIVE:
      The objective was to test the feasibility of adding tailored, computer-generated,
      step-count feedback to a face-to-face nutritional counseling weight loss
      intervention. METHODS: We recruited 12 participants, 4 from each of three
      Department of Veterans Affairs medical centers. There were 11 male participants
      and 1 female participant. Each had a body mass index of 30 or greater and at
      least one of the following cardiovascular disease risk factors: diabetes,
      hypertension, hypercholesterolemia, obesity, or coronary artery disease.
      Participants attended one-on-one counseling sessions with a registered dietitian
      for four sessions over three weeks. At the initial session, each participant
      received an enhanced pedometer to record time-stamped, step-count data.
      Participants wore the device daily throughout the intervention. At the three
      follow-up sessions, the dietitian uploaded the computer data, reviewed a Web
      based graphical display of step-count feedback, and helped set new walking goals.
      RESULTS: All 12 participants completed the program (100% attendance). Initial
      mean weight was 255 lbs (SD = 49 lbs), and weight loss was just over 4 lbs (n =
      12, paired t test, P = .004). Mean daily step counts during the first week
      averaged 6019 steps per day, increasing to an average of 7358 per day after the
      third week (average increase of 1339 steps per day, or 0.6 miles, or 12 minutes
      of walking, n = 10, paired t test, P = .04). CONCLUSIONS: Enhanced pedometer
      feedback in conjunction with nutritional counseling is feasible and results in
      significant weight loss and increased walking among individuals at high risk for
      cardiovascular disease.

PMID- 16403721
TI  - Parent-child interaction using a mobile and wireless system for blood glucose
      monitoring.
AB  - BACKGROUND: Children with type 1 diabetes and their parents face rigorous
      procedures for blood glucose monitoring and regulation. Mobile telecommunication
      systems show potential as an aid for families' self-management of diabetes.
      OBJECTIVE: A prototype designed to automatically transfer readings from a child's
      blood glucose monitor to their parent's mobile phone was tested. In this
      formative stage of development, we sought insights into the appropriateness of
      the concept, feasibility of use, and ideas for further development and research.
      METHODS: During four months, a self-selected sample of 15 children (aged 9 to 15
      years) with type 1 diabetes and their parents (n = 30) used the prototype
      approximately three times daily. Parent and child experiences were collected
      through questionnaires and through interviews with 9 of the parents. RESULTS:
      System use was easily integrated into everyday life, and parents valued the sense
      of reassurance offered by the system. Parents' ongoing struggle to balance
      control of their children with allowing independence was evident. For children
      who measured regularly, use appeared to reduce parental intrusions. For those who
      measured irregularly, however, parental reminders (eg, "nagging") appeared to
      increase. Although increased reminders could be considered a positive outcome,
      they can potentially increase parent-child conflict and thus also undermine
      proper metabolic control. Parents felt that system appropriateness tapered off
      with the onset of adolescence, partly due to a potential sense of surveillance
      from the child's perspective that could fuel oppositional behavior. Parental
      suggestions for further developments included similar alerts of irregular insulin
      dosages and automatically generated dietary and insulin dosage advice.
      CONCLUSIONS: User enthusiasm suggests that such systems might find a consumer
      market regardless of whether or not they ultimately improve health outcomes.
      Thus, more rigorous studies are warranted to inform guidelines for appropriate
      use. Potentially fruitful approaches include integrating such systems with theory
      based parenting interventions and approaches that can aid in interpreting and
      responding to experiences of surveillance, virtual presence, and balances of
      power in e-mediated relationships.

PMID- 16403722
TI  - Mobile eHealth interventions for obesity: a timely opportunity to leverage
      convergence trends.
AB  - Obesity is often cited as the most prevalent chronic health condition and highest
      priority public health problem in the United States. There is a limited but
      growing body of evidence suggesting that mobile eHealth behavioral interventions,
      if properly designed, may be effective in promoting and sustaining successful
      weight loss and weight maintenance behavior changes. This paper reviews the
      current literature on the successes and failures of public health, provider
      administered, and self-managed behavioral health interventions for weight loss.
      The prevailing theories of health behavior change are discussed from the
      perspective of how this knowledge can serve as an evidence base to inform the
      design of mobile eHealth weight loss interventions. Tailored informational
      interventions, which, in recent years, have proven to be the most effective form
      of conventional health behavior intervention for weight loss, are discussed.
      Lessons learned from the success of conventional tailored informational
      interventions and the early successes of desktop computer-assisted self-help
      weight management interventions are presented, as are design principles suggested
      by Social Cognitive Theory and the Social Marketing Model. Relevant computing and
      communications technology convergence trends are also discussed. The recent
      trends in rapid advancement, convergence, and public adoption of Web-enabled
      cellular telephone and wireless personal digital assistant (PDA) devices provide
      timely opportunities to deliver the mass customization capabilities, reach, and
      interactivity required for the development, administration, and adoption of
      effective population-level eHealth tailored informational interventions for
      obesity.

PMID- 16403723
TI  - Automated assessment of the quality of depression websites.
AB  - BACKGROUND: Since health information on the World Wide Web is of variable
      quality, methods are needed to assist consumers to identify health websites
      containing evidence-based information. Manual assessment tools may assist
      consumers to evaluate the quality of sites. However, these tools are poorly
      validated and often impractical. There is a need to develop better consumer
      tools, and in particular to explore the potential of automated procedures for
      evaluating the quality of health information on the web. OBJECTIVE: This study
      (1) describes the development of an automated quality assessment procedure (AQA)
      designed to automatically rank depression websites according to their evidence
      based quality; (2) evaluates the validity of the AQA relative to human rated
      evidence-based quality scores; and (3) compares the validity of Google PageRank
      and the AQA as indicators of evidence-based quality. METHOD: The AQA was
      developed using a quality feedback technique and a set of training websites
      previously rated manually according to their concordance with statements in the
      Oxford University Centre for Evidence-Based Mental Health's guidelines for
      treating depression. The validation phase involved 30 websites compiled from the
      DMOZ, Yahoo! and LookSmart Depression Directories by randomly selecting six sites
      from each of the Google PageRank bands of 0, 1-2, 3-4, 5-6 and 7-8. Evidence
      based ratings from two independent raters (based on concordance with the Oxford
      guidelines) were then compared with scores derived from the automated AQA and
      Google algorithms. There was no overlap in the websites used in the training and
      validation phases of the study. RESULTS: The correlation between the AQA score
      and the evidence-based ratings was high and significant (r=0.85, P<.001).
      Addition of a quadratic component improved the fit, the combined linear and
      quadratic model explaining 82 percent of the variance. The correlation between
      Google PageRank and the evidence-based score was lower than that for the AQA.
      When sites with zero PageRanks were included the association was weak and non
      significant (r=0.23, P=.22). When sites with zero PageRanks were excluded, the
      correlation was moderate (r=.61, P=.002). CONCLUSIONS: Depression websites of
      different evidence-based quality can be differentiated using an automated system.
      If replicable, generalizable to other health conditions and deployed in a
      consumer-friendly form, the automated procedure described here could represent an
      important advance for consumers of Internet medical information.

PMID- 16403725
TI  - Law & psychiatry: Twenty-five years of law and psychiatry.
AB  - Dr. Appelbaum reviews the past 25 years of the Law & Psychiatry column, of which
      he has been the editor since the column's initiation by John Talbott, M.D. The
      column has included contributions from Dr. Appelbaum as well as from various
      other mental health professionals and lawyers with various specializations.
      Citation of the column in other articles suggests that it is meeting a need for
      timely description and analysis of major legal developments that affect the field
      of psychiatry and psychiatric patients. Dr. Appelbaum notes that the 104 columns
      published thus far reflect the evolution of legal concerns in psychiatry as well
      as the presence of core issues that have remained unchanged. He raises the
      question of what the next quarter century will hold, positing that mental health
      law will continue to reflect a tension between the interests of persons with
      mental illness and the public's fear of such individuals.

PMID- 16403724
TI  - Going, going, still there: using the WebCite service to permanently archive cited
      web pages.
AB  - Scholars are increasingly citing electronic "web references" which are not
      preserved in libraries or full text archives. WebCite is a new standard for
      citing web references. To "webcite" a document involves archiving the cited Web
      page through www.webcitation.org and citing the WebCite permalink instead of (or
      in addition to) the unstable live Web page. This journal has amended its
      "instructions for authors" accordingly, asking authors to archive cited Web pages
      before submitting a manuscript. Almost 200 other journals are already using the
      system. We discuss the rationale for WebCite, its technology, and how scholars,
      editors, and publishers can benefit from the service. Citing scholars initiate an
      archiving process of all cited Web references, ideally before they submit a
      manuscript. Authors of online documents and websites which are expected to be
      cited by others can ensure that their work is permanently available by creating
      an archived copy using WebCite and providing the citation information including
      the WebCite link on their Web document(s). Editors should ask their authors to
      cache all cited Web addresses (Uniform Resource Locators, or URLs)
      "prospectively" before submitting their manuscripts to their journal. Editors and
      publishers should also instruct their copyeditors to cache cited Web material if
      the author has not done so already. Finally, WebCite can process publisher
      submitted "citing articles" (submitted for example as eXtensible Markup Language
      [XML] documents) to automatically archive all cited Web pages shortly before or
      on publication. Finally, WebCite can act as a focussed crawler, caching
      retrospectively references of already published articles. Copyright issues are
      addressed by honouring respective Internet standards (robot exclusion files, no
      cache and no-archive tags). Long-term preservation is ensured by agreements with
      libraries and digital preservation organizations. The resulting WebCite Index may
      also have applications for research assessment exercises, being able to measure
      the impact of Web services and published Web documents through access and Web
      citation metrics.

PMID- 16403726
TI  - Innovations: Alcohol & drug abuse: Narcotics on the net: the availability of Web
      sites selling controlled substances.
AB  - The Internet is not only a vital medium for communication, entertainment, and
      commerce, but it is also an outlet for illicit drug sales. Although the U.S.
      Controlled Substances Act regulates access to certain drugs by requiring
      prescriptions, unique characteristics of the Internet create significant
      challenges for the enforcement of U.S. drug policies. In the late 1990s "no
      prescription Web sites" (NPWs) began to emerge, which allow persons to purchase
      drugs, such as opiates, without a prescription. Given the likely role of NPWs in
      increasing prescription drug abuse, health care professionals must develop and
      disseminate strategies for helping patients who are affected by these Web sites.

PMID- 16403727
TI  - Innovations: Child & adolescent psychiatry: "Sweet are the uses of adversity": a
      transition program for children discharged from an inpatient unit.
AB  - A planning and implementation group was created to respond to a severe shortage
      of public-sector children's inpatient beds in New Orleans. This group identified
      a large gap in the continuum between the inpatient unit, with its wide range of
      resources, and the five traditional mental health centers that provided
      medication management as well as social work contacts on a weekly to monthly
      basis. A unique "transition program" was created that has effectively bridged the
      gap between the hospital and the rest of the community. Data on the program,
      including clinical functioning data, improvement and severity ratings, data on
      recidivism, aftercare compliance ratings, and satisfaction surveys, have
      demonstrated that the program had a positive impact.

PMID- 16403729
TI  - Committee reports & consensus statements.

PMID- 16403728
TI  - Is a consensus possible on stem cell research? Moral and political obstacles.

PMID- 16403730
TI  - Position statements & ADA statements.

PMID- 16403731
TI  - Actin binding to the central domain of WASP/Scar proteins plays a critical role
      in the activation of the Arp2/3 complex.
AB  - The Arp2/3 complex nucleates and cross-links actin filaments at the leading edge
      of motile cells, and its activity is stimulated by C-terminal regions of
      WASP/Scar proteins, called VCA domains. VCA domains contain a verprolin homology
      sequence (V) that binds monomeric actin and central (C) and acidic sequences (A)
      that bind the Arp2/3 complex. Here we show that the C domain binds to monomeric
      actin with higher affinity (K(d) = 10 microm) than to the Arp2/3 complex (K(d) >
      200 microm). Nuclear magnetic resonance spectroscopy reveals that actin binds to
      the N-terminal half of the C domain and that both the V and C domains can bind
      actin independently and simultaneously, indicating that they interact with
      different sites. Mutation of conserved hydrophobic residues in the actin-binding
      interface of the C domain disrupts activation of the Arp2/3 complex but does not
      alter affinity for the complex. By chemical cross-linking the C domain interacts
      with the p40 subunit of the Arp2/3 complex and, by fluorescence polarization
      anisotropy, the binding of actin and the Arp2/3 complex are mutually exclusive.
      Our results indicate that both actin and Arp2/3 binding are important for C
      domain function but that the C domain does not form a static bridge between the
      two. We propose a model for activation of the Arp2/3 complex in which the C
      domain first primes the complex by inducing a necessary conformational change and
      then initiates nucleus assembly by bringing an actin monomer into proximity of
      the primed complex.

PMID- 16403732
TI  - Test case of the long term preliminary performance assessment for the L&IL
      radioactive waste repository Baita Bihor, Romania.
AB  - The paper presents the assessment methodology developed in the framework of the
      long-term preliminary performance assessment of Baita Bihor Romanian national low
      level and intermediate-level radioactive waste repository. Conservative
      assumptions, input parameters and tools used in this approach reflect limitations
      imposed by the current assessment capability, as well as limited knowledge and
      understanding of the disposal system. The resultant dose rates are presented and
      analysed. Conclusions are drawn relating to the safety of the repository.

PMID- 16403734
TI  - Failure to thrive: a consequence of undernutrition.

PMID- 16403733
TI  - Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF
      kappaB and Akt as targets.
AB  - Xanthohumol (XN), the principal flavonoid of the hop plant (Humulus lupulus L.)
      and a constituent of beer, has been suggested to have potential cancer
      chemopreventive activities. We have observed that most cancer chemopreventive
      agents show antiangiogenic properties in vitro and in vivo, a concept we termed
      "angioprevention." Here we show for the first time that XN can inhibit growth of
      a vascular tumor in vivo. Histopathology and in vivo angiogenesis assays
      indicated that tumor angiogenesis inhibition was involved. Further, we show the
      mechanisms for its inhibition of angiogenesis in vivo and related endothelial
      cell activities in vitro. XN repressed both the NF-kappaB and Akt pathways in
      endothelial cells, indicating that components of these pathways are major targets
      in the molecular mechanism of XN. Moreover, using in vitro analyses, we show that
      XN interferes with several points in the angiogenic process, including inhibition
      of endothelial cell invasion and migration, growth, and formation of a network of
      tubular-like structures. Our results suggest that XN can be added to the
      expanding list of antiangiogenic chemopreventive drugs whose potential in cancer
      prevention and therapy should be evaluated.

PMID- 16403735
TI  - Minimal enteral feeding within 3 d of birth in prematurely born infants with
      birth weight < or = 1200 g improves bone mass by term age.
AB  - BACKGROUND: Evidence-based practice guidelines for aggressive nutritional
      intervention by using parenteral amino acids (AAs) and minimal enteral feeding
      (MEF) as early as the first day of life have not been tested for benefits to bone
      mass. OBJECTIVE: We investigated whether early introduction of parenteral AAs and
      MEF improves growth and bone mass achieved by term age in infants born
      prematurely. DESIGN: Twenty-seven infants who were < or = 1200 g and < or = 32 wk
      gestation at birth were randomly assigned by using a 2 x 2 design to treatment of
      either 1 g AAs/kg within the first 24 h or 12 mL MEF x kg(-1) x d(-1) within the
      first 72 h of life. Nutrition and growth were documented during hospitalization,
      and bone mineral content (BMC) of lumbar spine 1-4, femur, and whole body was
      measured at term age. Biomarkers of bone metabolism were measured at weeks 1, 3,
      and 5 and at discharge. Statistical analysis was conducted by using 2 x 2
      analysis of variance for intent to treat and for infants receiving protocol
      nutrition. RESULTS: Over the first 14 d of life, a main effect of early AAs
      elevated total intake of protein, and a main effect of early MEF was a higher
      frequency of MEF volumes exceeding > 12 mL x kg(-1) x d(-1). Main effects on
      growth were not evident. An interaction effect was observed for osteocalcin
      whereby early AAs or MEF alone elevated osteocalcin. A main effect of early MEF
      yielded higher BMC of spine and femur. CONCLUSION: Early aggressive nutrition
      support with MEF enhances BMC in premature infants, but early MEF or AAs do not
      improve growth.

PMID- 16403737
TI  - Oryzabase. An integrated biological and genome information database for rice.
AB  - The aim of Oryzabase is to create a comprehensive view of rice (Oryza sativa) as
      a model monocot plant by integrating biological data with molecular genomic
      information (http://www.shigen.nig.ac.jp/rice/oryzabase/top/top.jsp). The
      database contains information about rice development and anatomy, rice mutants,
      and genetic resources, especially for wild varieties of rice. The anatomical
      description of rice development is unique and is the first known representation
      for rice. Developmental and anatomical descriptions include in situ gene
      expression data serving as stage and tissue markers. The systematic presentation
      of a large number of rice mutant and mutant trait genes is indispensable, as is
      description of research in wild strains, core collections, and their detailed
      characterization. Several genetic, physical, and expression maps with full genome
      and cDNA sequences are also combined with biological data in Oryzabase. These
      datasets, when pooled together, could provide a useful tool for gaining greater
      knowledge about the life cycle of rice, the relationship between phenotype and
      gene function, and rice genetic diversity. For exchanging community information,
      Oryzabase publishes the Rice Genetics Newsletter organized by the Rice Genetics
      Cooperative and provides a mailing service, rice-e-net/rice-net.

PMID- 16403736
TI  - Agroinjection of tomato fruits. A tool for rapid functional analysis of
      transgenes directly in fruit.
AB  - Transient expression of foreign genes in plant tissues is a valuable tool for
      plant biotechnology. To shorten the time for gene functional analysis in fruits,
      we developed a transient methodology that could be applied to tomato (Solanum
      lycopersicum cv Micro Tom) fruits. It was found that injection of Agrobacterium
      cultures through the fruit stylar apex resulted in complete fruit infiltration.
      This infiltration method, named fruit agroinjection, rendered high levels of 35S
      Cauliflower mosaic virus-driven beta-glucuronidase and yellow fluorescence
      protein transient expression in the fruit, with higher expression levels around
      the placenta and moderate levels in the pericarp. Usefulness of fruit
      agroinjection was assayed in three case studies: (1) the heat shock regulation of
      an Arabidopsis (Arabidopsis thaliana) promoter, (2) the production of recombinant
      IgA antibodies as an example of molecular farming, and (3) the virus-induced gene
      silencing of the carotene biosynthesis pathway. In all three instances, this
      technology was shown to be efficient as a tool for fast transgene expression in
      fruits.

PMID- 16403738
TI  - U.S. hospitals: examining their fraying social contract.

PMID- 16403740
TI  - Could U.S. hospitals go the way of U.S. airlines?
AB  - The market for hospital services, like global markets in general, is becoming
      more competitive. Increased price transparency and focused competition can
      squeeze out inefficiencies, restraining prices and making some consumers better
      off. But competition can have a dark side. U.S. hospitals can treat Medicare and
      Medicaid patients at less than cost, care for the uninsured, and provide other
      money-losing services because they can cross-subsidize. By 2025 the need for
      general hospitals to cross-subsidize will greatly in-crease, but their ability to
      do so will be diminished. U.S. hospitals could begin to resemble U.S. airlines:
      severely cutting costs, eliminating services, and suffering financial
      instability.

PMID- 16403741
TI  - The cost-shift payment 'hydraulic': foundation, history, and implications.
AB  - The cost-shift payment "hydraulic" is an integral component of the fragmented
      U.S. health care financing system. If private payers' acceptance of the cost
      shifting burden were to erode, our system of health care financing could become
      unstable. This is especially true for the hospital industry. In this paper we
      provide a series of examples of cost shifting and a historical profile of the
      cost shift in the hospital industry since 1980, noting that cost-shifting
      pressures seem to fluctuate over time and across health care markets. Cost
      shifting need not be dollar per dollar, as hospitals can absorb some degree of
      cost-shifting pressure through increased efficiency and decreases in service
      provision.

PMID- 16403742
TI  - Paying for hospitals' community service.
AB  - U.S. hospitals incur costs of $25-$50 billion annually in providing "community
      service," primarily in the form of health professions education and standby
      costs. They also provide approximately $30 billion in uncompensated care.
      Historically, such "community service" costs have been subsidized explicitly by
      Medicare and implicitly in the prices paid by private payers. The sustainability
      of that system is highly uncertain. With a growing number of uninsured patients,
      allocating nonreimbursable costs to paying customers can create a "death spiral,"
      in which fewer paying customers bear a larger proportion of such costs. The
      obvious solutions to this problem all have serious limitations.

PMID- 16403744
TI  - The precarious pricing system for hospital services.
AB  - Over the past twenty-five years, the average ratio of hospital charges for
      services (gross revenues) to payments received (net revenues) has grown from 1.1
      to 2.6. This reflects a transition from predominantly cost- and charge-based
      payment systems to regulated and negotiated fixed payments. Hospitals have been
      able to squeeze additional revenues from remaining charge-based payers and
      services by sharply increasing charges, negatively affecting the uninsured.
      Although protection of the uninsured seems warranted, it might be difficult to
      regulate hospital pricing systems in isolation from other controversial issues,
      such as the acceptability of cross-subsidies and the role of market forces.

PMID- 16403745
TI  - The pricing of U.S. hospital services: chaos behind a veil of secrecy.
AB  - Although Americans and foreigners alike tend to think of the U.S. health care
      system as being a "market-driven" system, the prices actually paid for health
      care goods and services in that system have remained remarkably opaque. This
      paper describes how U.S. hospitals now price their services to the various third
      party payers and self-paying patients, and how that system would have to be
      changed to accommodate the increasingly popular concept of "consumer-directed
      health care."

PMID- 16403746
TI  - The future of medicare hospital payment.
AB  - The combination of health care cost growth exceeding general inflation and the
      swelling of beneficiary rolls with baby boomers will create fiscal pressure for
      Medicare. Despite dramatic declines in the growth of hospital costs following the
      introduction of Medicare's prospective payment system (PPS), the growth in
      Medicare hospital spending per beneficiary has been close to three times the
      overall rate of inflation since 2000. This paper examines issues related to
      Medicare's using its pricing policies to more aggressively pursue hospital cost
      containment. I discuss the need to calibrate payments to reflect expected
      necessary costs to reduce potential effects on beneficiaries' access, quality of
      care, or technological improvements.

PMID- 16403747
TI  - Hospital payment systems: will payers like the future better than the past?
AB  - Unsustainable health care cost growth has forced payers to reexamine goals for
      hospital payment systems. Employers want simplicity and transparency, with
      comparative performance data available in the public domain. Insurers favor
      simplicity but prefer to keep the analysis of comparative performance data and
      pricing private. Thirty-five pay-for-performance experiments have been devised in
      the private sector, to reward hospitals for higher quality and move toward more
      effective payment systems. Definitive results are not yet known, and caveats
      remain, but early signs are promising. We develop three scenarios for future
      hospital payment systems and identify policy actions to improve outcomes.

PMID- 16403749
TI  - Specialty hospitals: a problem or a symptom?
AB  - The Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003
      imposed a moratorium on new physician-owned specialty hospitals, which expired in
      June 2005. Recent administrative decisions have effectively extended the
      moratorium as it applies to Medicare payment, and the debate continues over
      whether specialty hospitals are good, bad, or indifferent. This paper reviews the
      findings in two congressionally mandated reports on specialty hospitals, the
      services they provide, and their impact on their patients and communities. These
      findings are used to highlight the major policy issues to be addressed-issues
      that go beyond whether specialty hospitals should be allowed.

PMID- 16403750
TI  - Specialty versus community hospitals: referrals, quality, and community benefits.
AB  - In this paper we compare physician referral patterns, quality, patient
      satisfaction, and community benefits of physician-owned specialty versus peer
      competitor hospitals. Our results are based on evidence gathered from site visits
      to six markets, 2003 Medicare claims, patient focus groups, and Internal Revenue
      Service data. Although physician-owners are more likely than others to refer to
      their own facilities and treat a healthier population, there are rationales for
      these patterns aside from motives for profit. Specialty hospitals provide
      generally high-quality care to satisfied patients. Uncompensated care plus
      specialty hospitals' taxes represent a greater burden, in percentage terms, than
      community benefits provided by nonprofit providers.

PMID- 16403751
TI  - Do physician-owned cardiac hospitals increase utilization?
AB  - This paper looks at whether physicians' investment in heart hospitals during 1997
      2001 was followed by an increase in the number of relatively profitable cardiac
      surgeries paid for by Medicare or in a shift toward operating on healthier (more
      profitable) Medicare patients. Although markets with physician-owned hospitals
      had slightly above-average growth rates in profitable cardiac surgeries during
      this period, the magnitude of the increase was small and statistically
      significant only for bypass surgery. There was no increase in the proportion of
      surgeries performed on healthier patients. These findings contrast with earlier
      studies of less-invasive services such as diagnostic imaging.

PMID- 16403752
TI  - Intolerable risk, irreparable harm: the legacy of physician-owned specialty
      hospitals.
AB  - Issues of physician ownership and referral could cause major shifts in the
      structure of medical care and make the financing of U.S. hospital services
      problematic. The Medicare Prescription Drug, Improvement, and Modernization Act
      (MMA) of 2003 mandated research on this matter and applied an eighteen-month
      moratorium against self-referral to allow policymakers to consider the issue.
      Research findings thus far confirm that physicians' ownership and referral
      present conflicts of interest through medical and economic patient selection and
      potentially excessive utilization. The policy response must prevent these results
      and preserve fair competition among hospitals.

PMID- 16403753
TI  - National health spending in 2004: recent slowdown led by prescription drug
      spending.
AB  - U.S. health care spending rose 7.9 percent to $1.9 trillion in 2004, or $6,280
      per person. Health spending accounted for 16 percent of gross domestic product
      (GDP), nearly the same as in 2003. The pace of health spending growth has slowed,
      compared with the 2000-2002 period, for both public and private payers. Hospital
      spending accounted for 30 percent of the aggregate increase between 2002 and
      2004, and prescription drugs accounted for an 11 percent share-smaller than its
      share of the increase in recent years and much slower in absolute terms.

PMID- 16403754
TI  - Evidence of cost shifting in California hospitals.
AB  - We used 1993-2001 data from private hospitals in California to investigate
      whether decreases in Medicare and Medicaid prices were associated with increases
      in prices paid for privately insured patients. We found that a 1 percent relative
      decrease in the average Medicare price is associated with a 0.17 percent increase
      in the corresponding price paid by privately insured patients; similarly, a 1
      percent relative reduction in the average Medicaid price is associated with a
      0.04 percent increase. These relationships imply that cost shifting from Medicare
      and Medicaid to private payers accounted for 12.3 percent of the total increase
      in private payers' prices from 1997 to 2001.

PMID- 16403755
TI  - Nurse staffing in hospitals: is there a business case for quality?
AB  - We construct national estimates of the cost of increasing hospital nurse staffing
      and associated reductions in days, deaths, and adverse outcomes. Raising the
      proportion of nursing hours provided by registered nurses (RNs) without
      increasing total nursing hours is associated with a net reduction in costs.
      Increasing nursing hours, with or without increasing the proportion of hours
      provided by RNs, reduces days, adverse outcomes, and patient deaths, but with a
      net increase in hospital costs of 1.5 percent or less at the staffing levels
      modeled. Whether or not staffing should be increased depends on the value
      patients and payers assign to avoided deaths and complications.

PMID- 16403756
TI  - How can employment-based benefits help the nurse shortage?
AB  - During a labor shortage, employment-based benefits can be used to recruit and
      retain workers. This paper provides data on the availability of benefits to
      registered nurses (RNs), reports on how health care leaders are approaching the
      provision of employment-based benefits for nurses, and considers what nurses have
      to say in focus groups about benefits. Because of the ongoing nurse shortage,
      many employers are trying to enhance the benefits they offer to support
      recruitment and retention efforts. We offer recommendations for health care
      leaders that follow from our findings about the current state of nurses'
      employment-based benefits.

PMID- 16403757
TI  - From capitation to fee-for-service in cincinnati: a physician group responds to a
      changing marketplace.
AB  - The experience of Group Health Associates, a multispecialty practice physician
      group in Cincinnati, Ohio, offers an important case study of how payment
      incentives and market realities can change the way physicians practice medicine.
      After nearly thirty years as a capitation-based medical group, these physicians
      recently switched completely to fee-for-service reimbursement-not willingly, but
      in response to an evolving marketplace. Their new business strategy seeks to
      create a case for being paid for performance and treating the chronically ill.

PMID- 16403758
TI  - 'Can you prescribe something?'.

PMID- 16403759
TI  - Bringing Vincent home.

PMID- 16403760
TI  - Medicaid/SCHIP cuts and hospital emergency department use.
AB  - This paper uses data from the 2000-01 and 2003 Community Tracking Study household
      surveys to examine how decreases in enrollment in Medicaid and the State
      Children's Health Insurance Program (SCHIP) and increases in the number of
      uninsured people would affect the volume and distribution of emergency department
      (ED) use among low-income people. A decrease in Medicaid/SCHIP enrollment would
      lead to an increase in ED visits by the uninsured but little change in overall ED
      volume. The results suggest that cost containment efforts that reduce eligibility
      and enrollment will achieve cost savings largely by reducing access and shifting
      costs away from Medicaid/SCHIP.

PMID- 16403762
TI  - Medical savings accounts: what story do the data tell?
AB  - Fewer than a quarter-million tax units had reported a medical savings account
      (MSA) by the end of 2001. Nearly one-quarter of those having an MSA reported
      being previously uninsured. The tax data support the prediction that higher
      income taxpayers are more likely than others to be MSA consumers. Surprisingly,
      the middle-aged had the greatest predicted MSA demand, even after income and
      marginal tax rate were controlled for. There is mixed evidence as to whether the
      account was treated as a savings vehicle. For those who continued their accounts,
      their build-up was generally sufficient to offset a year or two of future medical
      expenses below the deductible.

PMID- 16403761
TI  - How the new medicare drug benefit could affect vulnerable populations.
AB  - This study estimates how out-of-pocket drug costs could change for vulnerable
      populations (racial and ethnic minorities, the near-poor, and seniors with a
      greater burden of chronic conditions) who qualify for the standard Medicare drug
      benefit. Although the new benefit might be associated with modest-to-moderate
      declines in out-of-pocket spending for seniors who do not qualify for subsidies,
      the savings might not be shared equitably and therefore might not reduce
      financial barriers to medication use for these populations.

PMID- 16403763
TI  - Addressing the nurse shortage to improve the quality of patient care.
AB  - Nurses are the largest group of health care professionals providing direct
      patient care in hospitals, and the quality of care for hospital patients is
      strongly linked to the performance of nursing staff, according to an Institute of
      Medicine report. This paper describes the Robert Wood Johnson Foundation's
      (RWJF's) work in nursing, which focuses on improving the hospital work
      environment to attract and retain high-quality nursing staff, with the ultimate
      goal of improving patient care and outcomes in hospitals. Other organizations'
      efforts to address the nurse shortage are also explored.

PMID- 16403766
TI  - Asking why and what.

PMID- 16403765
TI  - No-fault compensation in New Zealand: harmonizing injury compensation, provider
      accountability, and patient safety.
AB  - In 1974 New Zealand jettisoned a tort-based system for compensating medical
      injuries in favor of a government-funded compensation system. Although the system
      retained some residual fault elements, it essentially barred medical malpractice
      litigation. Reforms in 2005 expanded eligibility for compensation to all
      "treatment injuries," creating a true no-fault compensation system. Compared with
      a medical malpractice system, the New Zealand system offers more-timely
      compensation to a greater number of injured patients and more-effective processes
      for complaint resolution and provider accountability. The unfinished business
      lies in realizing its full potential for improving patient safety.

PMID- 16403767
TI  - Yes to single-payer reform.

PMID- 16403768
TI  - Creating the future.

PMID- 16403769
TI  - Asking why and what: the authors respond.

PMID- 16403770
TI  - Options at the end of life.

PMID- 16403772
TI  - Efficacy of the farnesyltransferase inhibitor R115777 in a rat mammary tumor
      model: role of Ha-ras mutations and use of microarray analysis in identifying
      potential targets.
AB  - Rats treated with the alkylating agent methylnitrosourea (MNU) develop multiple,
      hormonally dependent mammary tumors. Roughly 50% of the tumors have Ha-ras
      mutation, whereas 50% do not. The MNU-induced rat mammary tumor model was
      employed to examine the therapeutic efficacy of the farnesyltransferase inhibitor
      (FTI), R115777, and to examine the use of genomics in identifying susceptible
      tumors as well as identifying genes whose expression are modulated by FTI
      treatment. In animals bearing palpable mammary tumors (< 7 mm diameter), we
      performed a surgical biopsy, and 3 days following the biopsy, rats were treated
      with R115777 (50 mg/kg body wt/day) by gavage. Tumors with Ha-ras mutations
      underwent profound regression, with nearly 90% showing complete regressions
      within 4 weeks. In contrast, the non-Ha-ras mutation-bearing tumors yielded a
      more variable response, although roughly half of the non-Ha-ras mutation tumors
      underwent significant regression. These results show that although all tumors
      appear to respond to the FTI inhibitor the tumors with Ha-ras mutations were
      exquisitely sensitive. We employed a microarray approach to define potential
      targets and the mechanism of action of R115777 in Ha-ras mutant or wildtype
      tumors following treatment with FTI. In addition, we determined whether gene
      expression prior to FTI treatment can be used to differentiate highly sensitive
      tumors (Ha-ras mutant) and tumors with variable sensitivity (Ha-ras wildtype).
      Untreated or FTI-treated (4 days at 50 mg/kg body wt) tumors (Ha-ras mutant or
      wildtype) were examined using oligonucleotide arrays. A significant number of
      genes were differentially expressed in control rat mammary tumors with or without
      an activated Ha-ras mutation, suggesting that a microarray analysis might
      differentiate highly sensitive and variably sensitive tumors. Most of the genes
      whose expressions were modulated by FTI in tumors were independent of Ha-ras
      status and were presumably modulated by effects on farnesylation of proteins
      other than Ha-ras. However, treatment of Ha-ras-mutated mammary tumors with
      R155777 results in preferential modulation of genes involved in ras-MAP kinase
      signal transduction pathway and in decreased expression of many genes involved
      with cell proliferation. In contrast, several classes of genes are altered in rat
      mammary tumors without a mutated Ha-ras, suggesting that non-ras targets are
      involved. Ras pathway related genes, p53, WT1 and PCNA, were preferentially
      modulated in Ha-ras-mutated tumors, whereas modulation of genes in the G-protein
      pathway, various cytochrome p450s and RB1 are involved in Ha-ras wildtype tumors.
      Elucidation of gene expression changes in FTI-treated or control rat mammary
      adenocarcinomas will help in identifying potential pharmacodynamic markers of FTI
      treatment as well as potential molecular targets of R115777 and other FTIs.

PMID- 16403771
TI  - Impact of adverse events on prescribing warfarin in patients with atrial
      fibrillation: matched pair analysis.
AB  - OBJECTIVES: To quantify the influence of physicians' experiences of adverse
      events in patients with atrial fibrillation who were taking warfarin. DESIGN:
      Population based, matched pair before and after analysis. SETTING: Database study
      in Ontario, Canada. PARTICIPANTS: The physicians of patients with atrial
      fibrillation admitted to hospital for adverse events (major haemorrhage while
      taking warfarin and thromboembolic strokes while not taking warfarin). Pairs of
      other patients with atrial fibrillation treated by the same physicians were
      selected. MAIN OUTCOME MEASURES: Odds of receiving warfarin by matched pairs of a
      given physician's patients (one treated after and one treated before the event)
      were compared, with adjustment for stroke and bleeding risk factors that might
      also influence warfarin use. The odds of prescriptions for angiotensin converting
      enzyme (ACE) inhibitor before and after the event was assessed as a neutral
      control. RESULTS: For the 530 physicians who had a patient with an adverse
      bleeding event (exposure) and who treated other patients with atrial fibrillation
      during the 90 days before and the 90 days after the exposure, the odds of
      prescribing warfarin was 21% lower for patients after the exposure (adjusted odds
      ratio 0.79, 95% confidence interval 0.62 to 1.00). Greater reductions in warfarin
      prescribing were found in analyses with patients for whom more time had elapsed
      between the physician's exposure and the patient's treatment. There were no
      significant changes in warfarin prescribing after a physician had a patient who
      had a stroke while not on warfarin or in the prescribing of ACE inhibitors by
      physicians who had patients with either bleeding events or strokes. CONCLUSIONS:
      A physician's experience with bleeding events associated with warfarin can
      influence prescribing warfarin. Adverse events that are possibly associated with
      underuse of warfarin may not affect subsequent prescribing.

PMID- 16403773
TI  - Role of calcineurin in exercise-induced mitochondrial biogenesis.
AB  - Raising cytosolic Ca2+ induces an increase in mitochondrial biogenesis in
      myotubes. This phenomenon mimics the adaptive responses of skeletal muscle to
      exercise. It has been hypothesized that increases in cytosolic Ca2+ during motor
      nerve activity stimulate mitochondrial biogenesis by activating calcineurin.
      Overexpression of constitutively active calcineurin increases expression of
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      and induction of genes involved in mitochondrial energy metabolism in muscle
      cells. The purpose of this study was to determine whether calcineurin plays a
      role in the stimulation of mitochondrial biogenesis by exercise. Rats were
      exercised on 5 successive days by means of swimming. Inhibition of calcineurin
      with cyclosporin did not prevent the exercise-induced increases in PGC-1alpha and
      a range of mitochondrial proteins. In contrast to the other mitochondrial
      proteins, the increases in cytochrome oxidase (COX)-I and -IV proteins were
      blocked by cyclosporin treatment. This inhibitory effect of cyclosporin occurred
      at the posttranscriptional level, as evidenced by normal increases in COX-I and
      COX-IV mRNAs in response to exercise in the cyclosporin-treated rats. This toxic
      effect of cyclosporin may account for the decrease in muscle respiratory capacity
      reported to occur with cyclosporin treatment. In conclusion, inhibition of
      calcineurin does not prevent the exercise-induced increase in mitochondrial
      biogenesis in skeletal muscles, providing evidence that the adaptive response is
      not mediated by activation of calcineurin.

PMID- 16403774
TI  - The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial
      glycemia independently of gastric emptying and insulin secretion in humans.
AB  - Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying
      and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7-36)
      amide is degraded to the metabolite GLP-1-(9-36) amide. The effects of GLP-1-(9
      36) amide in humans are less well characterized. Fourteen healthy volunteers were
      studied with intravenous infusion of GLP-1-(7-36) amide, GLP-1-(9-36) amide, or
      placebo over 390 min. After 30 min, a solid test meal was served, and gastric
      emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose,
      insulin, C-peptide, and glucagon measurements. Administration of GLP-1-(7-36)
      amide and GLP-1-(9-36) amide significantly raised total GLP-1 plasma levels.
      Plasma concentrations of intact GLP-1 increased to 21 +/- 5 pmol/l during the
      infusion of GLP-1-(7-36) amide but remained unchanged during GLP-1-(9-36) amide
      infusion [5 +/- 3 pmol/l; P < 0.001 vs. GLP-1-(7-36) amide administration]. GLP-1
      (7-36) amide reduced fasting and postprandial glucose concentrations (P < 0.001)
      and delayed gastric emptying (P < 0.001). The GLP-1 metabolite had no influence
      on insulin or C-peptide concentrations. Glucagon levels were lowered by GLP-1-(7
      36) amide but not by GLP-1-(9-36) amide. However, the postprandial rise in
      glycemia was reduced significantly (by approximately 6 mg/dl) by GLP-1-(9-36)
      amide (P < 0.05). In contrast, gastric emptying was completely unaffected by the
      GLP-1 metabolite. The GLP-1 metabolite lowers postprandial glycemia independently
      of changes in insulin and glucagon secretion or in the rate of gastric emptying.
      Most likely, this is because of direct effects on glucose disposal. However, the
      glucose-lowering potential of GLP-1-(9-36) amide appears to be small compared
      with that of intact GLP-1-(7-36) amide.

PMID- 16403775
TI  - Sp1/Sp3 binding is associated with cell-specific expression of the glucose
      dependent insulinotropic polypeptide receptor gene.
AB  - The physiological effects of glucose-dependent insulinotropic polypeptide (GIP)
      are mediated through specific receptors expressed on target cells. Because
      aberrant GIP receptor (GIPR) expression has been implicated in abnormal GIP
      responses associated with type 2 diabetes mellitus and food-induced Cushing's
      syndrome, we sought to identify factors that regulate the GIPR. We previously
      demonstrated that sequences between -1 and -100 of the GIPR gene were sufficient
      to direct transcription in a rat insulinoma cell line (RIN38). In the present
      study, we compared the 5'-flanking regions of the rat and human GIPR gene and
      demonstrated 88% identity within the first 92 bp. Subsequent serial deletion
      analyses showed that the region between -85 and -40 is essential for maximal
      promoter activity. Within this region, we identified three putative Sp1 binding
      motifs, located at positions -77, -60, and -50, that can specifically bind both
      Sp1 and Sp3. Whereas mutation of the Sp1 sites at -50 and -60 led to 36 and 40%
      reduction in promoter activity, respectively, mutation of the Sp1 motif at -70
      did not affect promoter activity. Cotransfection of S2 Schneider cells with GIPR
      luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated
      that both Sp1 and the long form of Sp3 activate transcription through binding to
      the Sp1 sites located between -100 and -40. Lastly, chromatin immunoprecipitation
      analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38
      cells. These results indicate that cell-specific expression of GIPR is associated
      with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter.

PMID- 16403776
TI  - The gastroenteroinsular response to glucose ingestion during postexercise
      recovery.
AB  - This study examined gastrointestinal hormone and peptide responses when glucose
      was ingested after prolonged exercise. Six endurance-trained male athletes ran on
      a treadmill for 2 h at 60% VO2 max. Immediately after the run, the athletes
      consumed 75 g of glucose in 250 ml of water (ExGLU) or flavored water as a
      placebo control (ExPL). On a separate visit, the athletes rested for 2 h and then
      consumed glucose (ConGLU). During the first 60 min of recovery from exercise
      alone (ExPL), plasma vasoactive intestinal peptide (VIP), gastrin, and glucagon
      like peptide-1 (GLP-1) all increased significantly, whereas glucose, insulin, and
      gastric inhibitory polypeptide (GIP) were unchanged from the immediate
      postexercise value. When glucose was ingested after exercise (ExGLU), glucose,
      insulin, VIP, gastrin, GLP-1, and GIP were all increased (P < 0.01). However,
      when glucose was ingested after resting for 2 h (ConGLU), VIP levels were
      unaffected, although glucose, insulin, gastrin, GLP-1, and GIP levels increased
      (P < 0.05). The plasma glucose response was greater (P < 0.03) and the plasma
      insulin response lower (P < 0.004) during ExGLU compared with ConGLU. There was a
      significantly higher (P < 0.01) VIP response during the initial period of
      recovery in ExGLU than there was with both ExPL and ConGLU. Plasma VIP showed a
      modest negative correlation with circulating glucose (r = -0.35, P < 0.03) and
      insulin (r = -0.37, P < 0.03) during the ExGLU recovery period. In summary, when
      glucose is ingested after prolonged exercise, there is mild insulin resistance
      and a corresponding rapid transitory increase in plasma VIP. These data suggest
      that VIP may play an important glucoregulatory role when glucose is ingested
      during the immediate postexercise recovery period.

PMID- 16403777
TI  - Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux
      during steady-state exercise.
AB  - The aim of this study was to determine whether the decreased muscle and blood
      lactate during exercise with hyperoxia (60% inspired O2) vs. room air is due to
      decreased muscle glycogenolysis, leading to decreased pyruvate and lactate
      production and efflux. We measured pyruvate oxidation via PDH, muscle pyruvate
      and lactate accumulation, and lactate and pyruvate efflux to estimate total
      pyruvate and lactate production during exercise. We hypothesized that 60% O2
      would decrease muscle glycogenolysis, resulting in decreased pyruvate and lactate
      contents, leading to decreased muscle pyruvate and lactate release with no change
      in PDH activity. Seven active male subjects cycled for 40 min at 70% VO2 peak on
      two occasions when breathing 21 or 60% O2. Arterial and femoral venous blood
      samples and blood flow measurements were obtained throughout exercise, and muscle
      biopsies were taken at rest and after 10, 20, and 40 min of exercise. Hyperoxia
      had no effect on leg O2 delivery, O2 uptake, or RQ during exercise. Muscle
      glycogenolysis was reduced by 16% with hyperoxia (267 +/- 19 vs. 317 +/- 21
      mmol/kg dry wt), translating into a significant, 15% reduction in total pyruvate
      production over the 40-min exercise period. Decreased pyruvate production during
      hyperoxia had no effect on PDH activity (pyruvate oxidation) but significantly
      decreased lactate accumulation (60%: 22.6 +/- 6.4 vs. 21%: 31.3 +/- 8.7 mmol/kg
      dry wt), lactate efflux, and total lactate production over 40 min of cycling.
      Decreased glycogenolysis in hyperoxia was related to an approximately 44% lower
      epinephrine concentration and an attenuated accumulation of potent phosphorylase
      activators ADPf and AMPf during exercise. Greater phosphorylation potential
      during hyperoxia was related to a significantly diminished rate of PCr
      utilization. The tighter metabolic match between pyruvate production and
      oxidation resulted in a decrease in total lactate production and efflux over 40
      min of exercise during hyperoxia.

PMID- 16403778
TI  - Measurement of gluconeogenesis by deuterated water: the effect of equilibration
      time and fasting period.
AB  - Fasting gluconeogenesis (GNG) is often quantified using the 2H2O technique, which
      is based on plasma 2H2O enrichment and ensuing enrichment of plasma glucose at
      the C5 and C2 positions. Fractional (fr)GNG can be calculated using the ratio of
      C5 to C2 enrichment or the ratio of C5 to plasma 2H2O enrichment. For the latter,
      equilibration of 2H2O and C2 is required. The optimal equilibration period of
      2H2O and C2 remains to be elucidated. In six healthy male subjects fasted for 18
      h, we studied the effects of 3-, 5-, and 15-h 2H2O incubation periods on 1) the
      equilibration of plasma 2H2O and C2 glucose enrichment, 2) the measurement of
      frGNG, and 3) C5 labeling of hepatic glycogen after 1 mg of glucagon
      administration. After 3-h 2H2O incubation, plasma 2H2O and C2 were not
      equilibrated, frGNG C5/2H2O and C5/C2 were also different as was gluconeogenesis
      calculated with C5/2H2O and C5/C2. After 5- and 15-h 2H2O incubation, plasma 2H2O
      and C2 were equilibrated, and frGNG C5/2H2O and C5/C2 were similar, as was GNG
      calculated with C5/2H2O and C5/C2. After glucagon administration, no difference
      of C5 enrichment was found between 3, 5, and 15 h of 2H2O incubation. In
      conclusion, for reliable measurement of GNG in healthy subjects with C5/2H2O
      incubation periods longer than 3 h are required. After 5- and 15-h 2H2O
      incubation, GNG can be reliably measured with C5/2H2O. Gluconeogenetic labeling
      of glycogen did not affect the results after 3, 5, or 15 h of 2H2O incubation.

PMID- 16403779
TI  - Effect of differing antecedent hypoglycemia on counterregulatory responses to
      exercise in type 1 diabetes.
AB  - Hypoglycemia frequently occurs during or after exercise in intensively treated
      patients with type 1 diabetes mellitus (T1DM), but the underlying mechanisms are
      not clear. In both diabetic and nondiabetic subjects, moderate hypoglycemia
      blunts counterregulatory responses to subsequent exercise, but it is unknown
      whether milder levels of hypoglycemia can exert similar effects in a dose
      dependent fashion. This study was designed to test the hypothesis that prior
      hypoglycemia of differing depths induces acute counterregulatory failure of
      proportionally greater magnitude during subsequent exercise in T1DM. Twenty-two
      T1DM patients (11 males/11 females, HbA1c 8.0 +/- 0.3%) were studied during 90
      min of euglycemic cycling exercise after two 2-h periods of previous day
      euglycemia or hypoglycemia of 3.9, 3.3, or 2.8 mmol/l (HYPO-3.9, HYPO-3.3, HYPO
      2.8, respectively). Patients' counterregulatory responses (circulating levels of
      neuroendocrine hormones, intermediary metabolites, substrate flux, tracer
      determined glucose kinetics, and cardiovascular measurements) were assessed
      during exercise. Identical euglycemia and basal insulin levels were successfully
      maintained during all exercise studies, regardless of blood glucose levels during
      the previous day. After day 1 euglycemia, patients displayed normal
      counterregulatory responses to exercise. Conversely, when identical exercise was
      performed after day 1 hypoglycemia of increasing depth, a progressively greater
      blunting of glucagon, catecholamine, cortisol, endogenous glucose production, and
      lipolytic responses to exercise was observed. This was paralleled by a graduated
      increase in the amount of exogenous glucose needed to maintain euglycemia during
      exercise. Our results demonstrate that acute counterregulatory failure during
      prolonged, moderate-intensity exercise may be induced in a dose-dependent fashion
      by differing depths of antecedent hypoglycemia starting at only 3.9 mmol/l in
      patients with T1DM.

PMID- 16403780
TI  - Regulation of human male germ cell death by modulators of ATP production.
AB  - The understanding of testicular physiology, pathology, and male fertility issues
      requires knowledge of male germ cell death and energy production. Here, we
      induced human male germ cell apoptosis (detected by Southern blot analysis of DNA
      fragmentation, TUNEL, activation of caspases-3 and -9, and electron microscopy)
      by incubating seminiferous tubule segments under hormone- and serum-free
      conditions. Inhibitors of complexes I to IV of mitochondrial respiration,
      exposure to anoxia, and inhibition of F0F1-ATPase (with oligomycin) decreased the
      ATP levels (analyzed by HPLC) and suppressed apoptosis at 4 h. Uncoupler 2,4
      dinitrophenol (DNP) and oligomycin combination also suppressed death at 4 h, as
      did the DNP alone. Inhibition of glycolysis by 2-deoxyglucose neither suppressed
      nor further induced apoptosis nor altered the antiapoptotic effects of the
      mitochondrial inhibitors. Furthermore, Fas system activation did not modify the
      effects of mitochondrial modulators. After 24 h, delayed male germ cell apoptosis
      was observed despite the presence of the mitochondrial inhibitors. We conclude
      that the mitochondrial ATP production machinery plays an important role in
      regulating in vitro-induced primary pathways of human male germ apoptosis. The
      ATP synthesized by the F0F1-ATPase seems to be the crucial death regulator,
      rather than any of the complexes (I-IV) alone, the functional electron transport
      chain, or the membrane potential. We also conclude that there seem to be
      secondary pathways of human testicular cell apoptosis that do not require
      mitochondrial ATP production. The present study emphasizes the role of the main
      catabolic pathways in the complex network of regulating events of male germ cell
      life and death.

PMID- 16403781
TI  - Physical training reverses the increased activity of the hepatic ketone body
      synthesis pathway in chronically diabetic rats.
AB  - This study was designed to examine whether the training-induced improvement in
      the plasma concentration of ketone bodies in experimental diabetes mellitus could
      be explained by changes in the activity of the hepatic ketone body synthesis
      pathway and/or the plasma free fatty acid levels. Diabetes mellitus was induced
      by an intravenous injection of streptozotocin (50 mg/kg), and training was
      carried out on a treadmill. The plasma concentration of beta-hydroxybutyric acid
      was increased (P < 0.001) in sedentary diabetic rats, and this was partly
      reversed by training (P < 0.001). The plasma concentration of free fatty acids
      was increased (P < 0.001) in sedentary diabetic rats, and this was reversed to
      normal by training (P < 0.001). Diabetes was also associated with an increased
      activity of the hepatic ketone body synthesis pathway. When the data are
      expressed as per total liver, physical training decreased the activity of the
      hepatic ketone body synthesis pathway by 18% in nondiabetic rats (P < 0.05) and
      by 22% in diabetic rats (P < 0.01), the activity present in trained diabetic rats
      being not statistically different from that of sedentary control rats. These data
      suggest that the beneficial effects of physical training on the plasma beta
      hydroxybutyric acid levels in the diabetic state are probably explained in part
      by a decrease in the activity of the hepatic ketone body synthesis pathway and in
      part by a decrease in plasma free fatty acid levels.

PMID- 16403782
TI  - Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of
      long-term body fat accrual on a high-fat diet.
AB  - The objective of this study was to investigate meal-related endocrine changes
      that permit one to identify Sprague-Dawley rats at normal weight that are prone
      (OP) vs. resistant (OR) to obesity. In blood collected via chronic cardiac
      catheters, a 2-h high-fat meal (HFM, 50% fat, 40 kcal) at dark onset caused a
      significant increase in leptin, insulin, and triglycerides compared with premeal
      levels. Similar to patterns in already obese compared with lean rats on a high
      fat diet, these meal-induced endocrine changes in normal-weight rats on lab chow
      were almost twofold larger in OP rats that, compared with OR rats, subsequently
      accumulated 100% more fat mass on a chronic high-fat diet. These exaggerated
      endocrine changes were similarly observed in blood collected using a simpler tail
      vein puncture procedure. In three separate experiments, the HFM-induced rise in
      leptin was found to be the strongest, positive correlate (r = +0.58, +0.62 and
      +0.64) of long-term body fat accrual. The lowest (2-5 ng/ml) vs. highest (6-9
      ng/ml) scores for this post-HFM leptin measurement identified distinct OR and OP
      subgroups, respectively, when they were similar in body weight (340-350 g),
      premeal leptin (2.6-3.4 ng/ml), and meal size (40 kcal). Subsequent tests in
      these normal-weight OP rats revealed a distinct characteristic compared with OR
      rats, namely, exaggerated HFM-induced rise in expression of the orexigenic
      peptide galanin in the paraventricular nucleus. Thus, with this HFM-induced
      leptin measurement, OP rats can be identified while still at normal weight and
      then investigated for mechanisms that contribute to their excessive body fat
      accrual on a high-fat diet.

PMID- 16403783
TI  - Influence of plasma protein on the potencies of inhibitors of cyclooxygenase-1
      and -2.
AB  - It is widely believed that the potencies of nonsteroid anti-inflammatory drugs
      (NSAIDs) as inhibitors of cyclooxygenase (COX) are influenced by protein binding
      in the extracellular fluid, since NSAIDs are bound to circulating albumin by well
      over 95%. This is an important point because the protein concentrations in
      synovial fluid and the central nervous system, which are sites of NSAID action,
      are markedly different from those in plasma. Here we have used a modified whole
      blood assay to compare the potencies of aspirin, celecoxib, diclofenac,
      indomethacin, lumiracoxib, meloxicam, naproxen, rofecoxib, sodium salicylate, and
      SC560 as inhibitors of COX-1 and COX-2 in the presence of differing
      concentrations of protein. The potencies of diclofenac, naproxen, rofecoxib, and
      salicylate, but not aspirin, celecoxib, indomethacin, lumiracoxib, meloxicam, or
      SC560, against COX-1 (human platelets) increased as protein concentrations were
      reduced. Varying protein concentrations did not affect the potencies of any of
      the drugs against COX-2, with the exception of sodium salicylate (A549 cells).
      Clearly, our findings show that the selectivity of inhibitors for COX-1 and COX
      2, which are taken to be linked to their efficacy and side effects, may change in
      different extracellular fluid conditions. In particular, selectivity in one body
      compartment does not demonstrate selectivity in another. Thus, whole-body safety
      or toxicity cannot be linked to one definitive measure of COX selectivity.

PMID- 16403784
TI  - Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone
      formation-related molecules.
AB  - Recently, the neurotoxicity of dopamine (DA) quinone formation by auto-oxidation
      of DA has focused on dopaminergic neuron-specific oxidative stress. In the
      present study, we examined DA quinone formation in methamphetamine (METH)-induced
      dopaminergic neuronal cell death using METH-treated dopaminergic cultured CATH.a
      cells and METH-injected mouse brain. In CATH.a cells, METH treatment dose
      dependently increased the levels of quinoprotein (protein-bound quinone) and the
      expression of quinone reductase in parallel with neurotoxicity. A similar
      increase in quinoprotein levels was seen in the striatum of METH (4 mg/kg X4,
      i.p., 2 h interval)-injected BALB/c mice, coinciding with reduction of DA
      transporters. Furthermore, pretreatment of CATH.a cells with quinone reductase
      inducer, butylated hydroxyanisole, significantly and dose-dependently blocked
      METH-induced elevation of quinoprotein, and ameliorated METH-induced cell death.
      We also showed the protective effect of tyrosinase, which rapidly oxidizes DA and
      DA quinone to form stable melanin, against METH-induced dopaminergic
      neurotoxicity in vitro and in vivo using tyrosinase null mice. Our results
      indicate that DA quinone formation plays an important role, as a dopaminergic
      neuron-specific neurotoxic factor, in METH-induced neurotoxicity, which is
      regulated by quinone formation-related molecules.

PMID- 16403785
TI  - Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through
      interaction with Mac-1 integrin.
AB  - Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent
      apolipoprotein(a) [apo(a)], which contains multiple repeats resembling
      plasminogen kringle 4, is considered a risk factor for the development of
      atherosclerotic disorders. However, the underlying mechanisms for the
      atherogenicity of Lp(a) are not completely understood. Here, we define a novel
      function of Lp(a) in promoting inflammatory cell recruitment that may contribute
      to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts
      with the beta2-integrin Mac-1, thereby promoting the adhesion of monocytes and
      their transendothelial migration in a Mac-1-dependent manner. Interestingly, the
      interaction between Mac-1 and Lp(a) was strengthened in the presence of
      proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4.
      Through its interaction with Mac-1, Lp(a) induced activation of the
      proinflammatory transcription factor NFkappaB, as well as the NFkappaB-related
      expression of prothrombotic tissue factor. In atherosclerotic coronary arteries
      Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating
      mononuclear cells. Taken together, our data demonstrate that Lp(a), via its
      apo(a) moiety, is a ligand for the beta2-integrin Mac-1, thereby facilitating
      inflammatory cell recruitment to atherosclerotic plaques. These observations
      suggest a novel mechanism for the atherogenic properties of Lp(a).

PMID- 16403786
TI  - Up-regulation of anandamide levels as an endogenous mechanism and a
      pharmacological strategy to limit colon inflammation.
AB  - Direct stimulation of cannabinoid CB1 receptors exerts a protective function in
      animal models of inflammatory bowel diseases (IBDs). However, it is not known
      whether endocannabinoids are up-regulated during IBDs in animals or humans, nor
      whether pharmacological elevation of endocannabinoid levels can be exploited
      therapeutically in these disorders. In this study we addressed these questions.
      Colon inflammation was induced in mice and rats with 2,4-dinitrobenzene- and
      2,4,6-trinitrobenzene sulfonic acids (DNBS and TNBS), respectively. DNBS-treated
      mice were treated chronically (for 3 or 7 days) with inhibitors of anandamide
      enzymatic hydrolysis (N-arachidonoyl-serotonin, AA-5-HT) or reuptake (VDM11), 10
      or 5 mg/kg, s.c., or with 5-amino-salicilic acid (5-ASA, 1.4 mg/kg, i.r.).
      Endocannabinoids (anandamide and 2-arachidonoylglycerol, 2-AG) were quantified in
      mouse colon, or in rat colon mucosa and submucosa, and in bioptic samples from
      the colon of patients with untreated ulcerative colitis, by liquid chromatography
      mass spectrometry. A strong elevation of anandamide, but not 2-AG, levels was
      found in the colon of DNBS-treated mice, in the colon submucosa of TNBS-treated
      rats, and in the biopsies of patients with ulcerative colitis. VDM-11
      significantly elevated anandamide levels in the colon of DNBS-treated mice and
      concomitantly abolished inflammation, whereas AA-5-HT did not affect
      endocannabinoid levels and was significantly less efficacious at attenuating
      colitis. 5-ASA also increased anandamide levels and abolished colitis. Thus,
      anandamide is elevated in the inflamed colon of patients with ulcerative colitis,
      as well as in animal models of IBDs, to control inflammation, and elevation of
      its levels with inhibitors of its cellular reuptake might be used in the
      treatment of IBDs.

PMID- 16403787
TI  - A transport mechanism for NAADP in a rat basophilic cell line.
AB  - NAADP is a second messenger that releases Ca2+ from intracellular stores.
      Surprisingly, it has been recently shown that extracellular application of NAADP
      is capable of inducing intracellular Ca2+ release. This is particularly important
      since the only mammalian enzymes known to catalyze the synthesis of this second
      messenger are located extracellularly. In the present manuscript, we have
      investigated whether mammalian cells possess a transport system capable of
      transporting this highly charged molecule into cells. Indeed, in RBL-2H3 cells, a
      rat basophilic cell line, and in SK-N-BE cells, a neuroblastoma cell line,
      [32P]NAADP is efficiently transported inside cells. NAADP transport is Na+ and
      Ca2+ dependent, is partially blocked by dipyridamole, but is unaffected by
      nitrobenzylthioinosine. RBL-2H3 cells also transport [32P]cADPR, but the
      differences in the pharmacological profile suggest that NAADP transport proceeds
      by a novel mechanism. Lastly, extracellular application of NAADP, but not NADP,
      induced a raise in intracellular Ca2+. This is the first demonstration that NAADP
      is transported into cells and highlights the possibility that, alongside a second
      messenger, NAADP might also act as an autocrine/paracrine signal.

PMID- 16403788
TI  - Haloferax volcanii PitA: an example of functional interaction between the Pfam
      chlorite dismutase and antibiotic biosynthesis monooxygenase families?
AB  - A curious fusion between chlorite dismutase-like and antibiotic biosynthesis
      monooxygenase-like domains within a single open reading frame has been revealed
      by both sequence homology and structural modeling in Haloferax volcanii PitA and
      its homologues in other halophilic archaea. While this fusion may reflect an
      environmental adaptation to life in hypersaline environments and hence one
      specific to haloarchaea, PitA and its homologues may represent a paradigm of
      biologically-relevant interplay between these two distinct activities in
      accordance with the Rosetta Stone approach.

PMID- 16403790
TI  - MZmine: toolbox for processing and visualization of mass spectrometry based
      molecular profile data.
AB  - SUMMARY: New additional methods are presented for processing and visualizing mass
      spectrometry based molecular profile data, implemented as part of the recently
      introduced MZmine software. They include new features and extensions such as
      support for mzXML data format, capability to perform batch processing for large
      number of files, support for parallel processing, new methods for calculating
      peak areas using post-alignment peak picking algorithm and implementation of
      Sammon's mapping and curvilinear distance analysis for data visualization and
      exploratory analysis. AVAILABILITY: MZmine is available under GNU Public license
      from http://mzmine.sourceforge.net/.

PMID- 16403789
TI  - GUUGle: a utility for fast exact matching under RNA complementary rules including
      G-U base pairing.
AB  - MOTIVATION: RNA secondary structure analysis often requires searching for
      potential helices in large sequence data. RESULTS: We present a utility program
      GUUGle that efficiently locates potential helical regions under RNA base pairing
      rules, which include Watson-Crick as well as G-U pairs. It accepts a positive and
      a negative set of sequences, and determines all exact matches under RNA rules
      between positive and negative sequences that exceed a specified length. The
      GUUGle algorithm can also be adapted to use a precomputed suffix array of the
      positive sequence set. We show how this program can be effectively used as a
      filter preceding a more computationally expensive task such as miRNA target
      prediction. AVAILABILITY: GUUGle is available via the Bielefeld Bioinformatics
      Server at http://bibiserv.techfak.uni-bielefeld.de/guugle

PMID- 16403791
TI  - Optimized multilayer perceptrons for molecular classification and diagnosis using
      genomic data.
AB  - MOTIVATION: Multilayer perceptrons (MLP) represent one of the widely used and
      effective machine learning methods currently applied to diagnostic classification
      based on high-dimensional genomic data. Since the dimensionalities of the
      existing genomic data often exceed the available sample sizes by orders of
      magnitude, the MLP performance may degrade owing to the curse of dimensionality
      and over-fitting, and may not provide acceptable prediction accuracy. RESULTS:
      Based on Fisher linear discriminant analysis, we designed and implemented an MLP
      optimization scheme for a two-layer MLP that effectively optimizes the
      initialization of MLP parameters and MLP architecture. The optimized MLP
      consistently demonstrated its ability in easing the curse of dimensionality in
      large microarray datasets. In comparison with a conventional MLP using random
      initialization, we obtained significant improvements in major performance
      measures including Bayes classification accuracy, convergence properties and area
      under the receiver operating characteristic curve (A(z)). SUPPLEMENTARY
      INFORMATION: The Supplementary information is available on
      http://www.cbil.ece.vt.edu/publications.htm

PMID- 16403792
TI  - A greedier approach for finding tag SNPs.
AB  - MOTIVATION: Recent studies have shown that a small subset of Single Nucleotide
      Polymorphisms (SNPs) (called tag SNPs) is sufficient to capture the haplotype
      patterns in a high linkage disequilibrium region. To find the minimum set of tag
      SNPs, exact algorithms for finding the optimal solution could take exponential
      time. On the other hand, approximation algorithms are more efficient but may fail
      to find the optimal solution. RESULTS: We propose a hybrid method that combines
      the ideas of the branch-and-bound method and the greedy algorithm. This method
      explores larger solution space to obtain a better solution than a traditional
      greedy algorithm. It also allows the user to adjust the efficiency of the program
      and quality of solutions. This algorithm has been implemented and tested on a
      variety of simulated and biological data. The experimental results indicate that
      our program can find better solutions than previous methods. This approach is
      quite general since it can be used to adapt other greedy algorithms to solve
      their corresponding problems. AVAILABILITY: The program is available upon
      request.

PMID- 16403793
TI  - Using a state-space model with hidden variables to infer transcription factor
      activities.
AB  - MOTIVATION: In a gene regulatory network, genes are typically regulated by
      transcription factors (TFs). Transcription factor activity (TFA) is more
      difficult to measure than gene expression levels are. Other models have extracted
      information about TFA from gene expression data, but without explicitly modeling
      feedback from the genes. We present a state-space model (SSM) with hidden
      variables. The hidden variables include regulatory motifs in the gene network,
      such as feedback loops and auto-regulation, making SSM a useful complement to
      existing models. RESULTS: A gene regulatory network incorporating, for example,
      feed-forward loops, auto-regulation and multiple-inputs was constructed with an
      SSM model. First, the gene expression data were simulated by SSM and used to
      infer the TFAs. The ability of SSM to infer TFAs was evaluated by comparing the
      profiles of the inferred and simulated TFAs. Second, SSM was applied to gene
      expression data obtained from Escherichia coli K12 undergoing a carbon source
      transition and from the Saccharomyces cerevisiae cell cycle. The inferred
      activity profile for each TF was validated either by measurement or by activity
      information from the literature. The SSM model provides a probabilistic framework
      to simulate gene regulatory networks and to infer activity profiles of hidden
      variables. AVAILABILITY: Supplementary data and Matlab code will be made
      available at the URL below. SUPPLEMENTARY INFORMATION:
      http://www.chems.msu.edu/groups/chan/ssm.zip.

PMID- 16403794
TI  - IWoCS: analyzing ribosomal intergenic transcribed spacers configuration and
      taxonomic relationships.
AB  - MOTIVATION: Lately the use of 16S-23S Intergenic Transcribed Spacer (ITS)
      sequences for bacterial typing purposes has increased. The presence of conserved
      regions like tRNA genes or boxes together with hypervariable regions allows
      performing intraspecific discrimination of very close bacterial strains. On the
      other hand this mosaic of variability makes the ITS a sequence difficult to
      analyze and compare. RESULTS: A software to study ITSs by a Word Count based
      System (IWoCS) is proposed. A large dataset of ITS was created (comprising 7355
      sequences). A database indicating all the occurrences of possible n-mers (tags),
      describing each ITS sequence, was created (with n going from 5 to 13) including
      32 061 819 entries. The database allows to analyze ITS sequences submitted by
      users using a web-based interface. The abundance in the database of each n-mer is
      given in a one-base sliding frame. A dominance plot reflects how common the tags
      are within different taxonomic levels. The obtained profile identifies highly
      repeated tags as evolutionarily conserved regions (like tRNA or boxes) or low
      frequency tags as regions specifically associated to taxonomic groups. The study
      of the dominance and abundance profiles combined with the taxonomy reports
      provides a novel tool for the use of the ITS in bacteria typing and
      identification. AVAILABILITY: The database is freely accessible at
      http://egg.umh.es/iwocs/.

PMID- 16403795
TI  - Short fuzzy tandem repeats in genomic sequences, identification, and possible
      role in regulation of gene expression.
AB  - MOTIVATION: Genomic sequences are highly redundant and contain many types of
      repetitive DNA. Fuzzy tandem repeats (FTRs) are of particular interest. They are
      found in regulatory regions of eukaryotic genes and are reported to interact with
      transcription factors. However, accurate assessment of FTR occurrences in
      different genome segments requires specific algorithm for efficient FTR
      identification and classification. RESULTS: We have obtained formulas for P
      values of FTR occurrence and developed an FTR identification algorithm
      implemented in TandemSWAN software. Using TandemSWAN we compared the structure
      and the occurrence of FTRs with short period length (up to 24 bp) in coding and
      non-coding regions including UTRs, heterochromatic, intergenic and enhancer
      sequences of Drosophila melanogaster and Drosophila pseudoobscura. Tandems with
      period three and its multiples were found in coding segments, whereas FTRs with
      periods multiple of six are overrepresented in all non-coding segment. Periods
      equal to 5-7 and 11-14 were characteristic of the enhancer regions and other non
      coding regions close to genes. AVAILABILITY: TandemSWAN web page, stand-alone
      version and documentation can be found at
      http://bioinform.genetika.ru/projects/swan/www/ SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 16403796
TI  - Copying nodes versus editing links: the source of the difference between genetic
      regulatory networks and the WWW.
AB  - We study two kinds of networks: genetic regulatory networks and the World Wide
      Web. We systematically test microscopic mechanisms to find the set of such
      mechanisms that optimally explain each networks' specific properties. In the
      first case we formulate a model including mainly random unbiased gene
      duplications and mutations. In the second case, the basic moves are website
      generation and rapid surf-induced link creation (/destruction). The different
      types of mechanisms reproduce the appropriate observed network properties. We use
      those to show that different kinds of networks have strongly system-dependent
      macroscopic experimental features. The diverging properties result from
      dissimilar node and link basic dynamics. The main non-uniform properties include
      the clustering coefficient, small-scale motifs frequency, time correlations,
      centrality and the connectivity of outgoing links. Some other features are
      generic such as the large-scale connectivity distribution of incoming links
      (scale-free) and the network diameter (small-worlds). The common properties are
      just the general hallmark of autocatalysis (self-enhancing processes), while the
      specific properties hinge on the specific elementary mechanisms. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics Online.

PMID- 16403797
TI  - Bayesian classifiers for detecting HGT using fixed and variable order markov
      models of genomic signatures.
AB  - MOTIVATION: Analyses of genomic signatures are gaining attention as they allow
      studies of species-specific relationships without involving alignments of
      homologous sequences. A naive Bayesian classifier was built to discriminate
      between different bacterial compositions of short oligomers, also known as DNA
      words. The classifier has proven successful in identifying foreign genes in
      Neisseria meningitis. In this study we extend the classifier approach using
      either a fixed higher order Markov model (Mk) or a variable length Markov model
      (VLMk). RESULTS: We propose a simple algorithm to lock a variable length Markov
      model to a certain number of parameters and show that the use of Markov models
      greatly increases the flexibility and accuracy in prediction to that of a naive
      model. We also test the integrity of classifiers in terms of false-negatives and
      give estimates of the minimal sizes of training data. We end the report by
      proposing a method to reject a false hypothesis of horizontal gene transfer.
      AVAILABILITY: Software and Supplementary information available at
      www.cs.chalmers.se/~dalevi/genetic_sign_classifiers/.

PMID- 16403798
TI  - Inferring global levels of alternative splicing isoforms using a generative model
      of microarray data.
AB  - MOTIVATION: Alternative splicing (AS) is a frequent step in metozoan gene
      expression whereby the exons of genes are spliced in different combinations to
      generate multiple isoforms of mature mRNA. AS functions to enrich an organism's
      proteomic complexity and regulates gene expression. Despite its importance, the
      mechanisms underlying AS and its regulation are not well understood, especially
      in the context of global gene expression patterns. We present here an algorithm
      referred to as the Generative model for the Alternative Splicing Array Platform
      (GenASAP) that can predict the levels of AS for thousands of exon skipping events
      using data generated from custom microarrays. GenASAP uses Bayesian learning in
      an unsupervised probability model to accurately predict AS levels from the
      microarray data. GenASAP is capable of learning the hybridization profiles of
      microarray data, while modeling noise processes and missing or aberrant data.
      GenASAP has been successfully applied to the global discovery and analysis of AS
      in mammalian cells and tissues. RESULTS: GenASAP was applied to data obtained
      from a custom microarray designed for the monitoring of 3126 AS events in mouse
      cells and tissues. The microarray design included probes specific for exon body
      and junction sequences formed by the splicing of exons. Our results show that
      GenASAP provides accurate predictions for over one-third of the total events, as
      verified by independent RT-PCR assays. SUPPLEMENTARY INFORMATION:
      http://www.psi.toronto.edu/GenASAP.

PMID- 16403799
TI  - Prevalence of health promotion policies in sports clubs in Victoria, Australia.
AB  - In recent years, some health agencies offered sponsorship to sporting
      associations to promote healthy environments by encouraging clubs to develop
      health-related policies. However, the extent to which these sponsorship contracts
      reach their stated aims is of concern. This study aimed to quantify levels of
      policy development and practice in sports clubs for each of five key health
      areas, namely smoke-free facilities, sun protection, healthy catering,
      responsible serving of alcohol and sports injury prevention. Representatives from
      932 Victorian sports clubs were contacted by telephone with 640 clubs (69%)
      participating in the survey. Results suggested that the establishment of written
      policies on the key health areas by sports clubs varied widely by affiliated
      sport and health area: 70% of all clubs with bar facilities had written policies
      on responsible serving of alcohol, ranging from 58% of tennis clubs to 100% of
      diving and surfing clubs. In contrast, approximately one-third of sports clubs
      had a smoke-free policy, with 36% of tennis, 28% of country football and 28% of
      men's cricket clubs having policy. Moreover, 34% of clubs overall had established
      sun protection policy, whereas clubs competing outside during summer months,
      [diving (86%) and life-saving (81%)] were most likely to have a written sun
      protection policy. Injury prevention policies were established in 30% of sports
      clubs, and were most common among football (56%), diving (43%) and life-saving
      (41%). This study suggests that policy development for health promotion can be
      achieved in sports clubs when it is well supported by health agencies and
      consideration is given to the appropriateness of the specific behaviours to be
      encouraged for a given sport. Communication between associations and clubs needs
      to be monitored by health agencies to ensure support and resources for policy
      development to reach the club level.

PMID- 16403800
TI  - Three mechanisms in the pathogenesis of pre-eclampsia suggested by over
      represented transcription factor-binding sites detected with comparative promoter
      analysis.
AB  - Microarray studies generating lists of genes with altered expression in placentas
      from pregnancies complicated with pre-eclampsia (PE) have so far been published
      in several different studies. Working under the assumption that altered gene
      expression in PE may be the result of altered expression of regulatory
      transcription factors (TFs), we looked for over-represented TF-binding sites
      (TFBSs)-which indicate the involvement of TFs in gene regulatory networks-in
      lists of genes (n = 143) compiled in these studies. We compared the prevalence of
      TFBSs in the promoter regions of 68 genes with the background prevalence of TFBSs
      in promoters of the human genome. The prevalence of the E47, sterol regulatory
      element binding protein (SREBP) and NFKB-p50 TFBSs was higher (P < 0.005) in the
      promoter sequences of the PE gene lists than in the background model. Each of
      these TFBSs could be implicated in the development of PE. The E47 protein is an E
      protein or basic helix-loop-helix (bHLH) TF. Data support the role of bHLHs in
      the differentiation of placental tissue. SREBP-1, a lipid-sensing sterol
      regulatory element-binding protein, is a critical regulator of fatty acid
      homeostasis in the placenta. The target genes of NFKB-p50 determine inflammatory
      response, and aberrant cytokine homeostasis is a further sign of PE. These TFs
      may provide an insight into the pathogenesis of the disease.

PMID- 16403801
TI  - A novel mechanism of protamine expression deregulation highlighted by abnormal
      protamine transcript retention in infertile human males with sperm protamine
      deficiency.
AB  - Sperm protamine deficiency has been associated with human male infertility.
      However, the aetiology of deregulated protamine expression remains elusive. The
      objective of this study was to evaluate the underlying aetiology of protamine
      deficiency in male infertility patients with deregulated protamine expression.
      Protamine-1 (P1) and protamine-2 (P2) protein concentrations were compared
      against P1 and P2 mRNA levels in the sperm of 166 male infertility patients and
      27 men of known fertility. Protamine protein concentrations were quantified by
      nuclear protein extraction, gel electrophoresis and densitometry analysis. Semi
      quantitative real-time RT-PCR was used to quantify P1 and P2 mRNA levels. P1 mRNA
      concentrations were significantly increased in patients underexpressing P1
      protein versus those with normal and increased P1 levels. In patients with an
      abnormally low ratio of P1 to P2 (P1/P2 <0.8), there was a significant increase
      in P1 mRNA retention. Patients underexpressing P2 also had significantly
      increased mean P2 mRNA levels, although the majority of these P2-deficient
      patients showed an increased frequency of significantly reduced P2 mRNA levels.
      This is the first study to concomitantly evaluate P1 and P2 protein and mRNA
      levels in mature human sperm. Abnormally elevated protamine mRNA retention
      appears to be associated with aberrant protamine expression in infertile human
      males. These data suggest that defects in protamine translation regulation may
      contribute to protamine deficiency in infertile males.

PMID- 16403802
TI  - Variations of the Amnionless gene in recurrent spontaneous abortions.
AB  - Recurrent spontaneous abortions (RSA) are estimated to affect 0.5-1% of couples
      trying to have a child. The causes of RSA are unknown in the majority of cases.
      This study aimed to determine whether homozygous mutations in the AMN gene in a
      fetus cause spontaneous abortions in humans, as they are known to cause
      spontaneous abortions in mice. The study was conducted by screening 40 couples
      and 5 women with three or more unexplained spontaneous abortions for heterozygous
      mutations in the AMN gene using denaturing high-performance liquid
      chromatography. Altogether, 3 exonic and 11 intronic sequence variations were
      found. There were no significant differences in the frequencies of the variations
      between the patients and a control group. One of the exonic variations was non
      synonymous, and three of the variations may affect gene splicing. None of the
      putative phenotype-affecting variations were found in both partners in any
      couple. These results indicate that RSA in the couples studied cannot be
      explained by homozygous AMN mutations in the fetus. However, two couples had
      different, potentially deleterious variations in both partners. If these
      variations have a phenotypic effect, the RSA experienced by these couples may be
      caused by mutations in the AMN gene. In addition, birthplaces of the patients'
      ancestors revealed some clustering, suggesting that some patients may carry a
      founder mutation in another gene which may contribute to RSA.

PMID- 16403803
TI  - Progesterone-dependent release of transforming growth factor-beta1 from
      epithelial cells enhances the endometrial decidualization by turning on the Smad
      signalling in stromal cells.
AB  - Endometrial decidualization results from the differentiation of stromal cells in
      an ovarian steroid-sensitive manner. Human endometrial tissues obtained from
      fertile women at various stages of the menstrual cycle were subjected to
      immunohistochemistry to localize the components of the transforming growth factor
      beta (TGF-beta) system. TGF-beta receptor-I and -II expression was higher in
      stromal cells than in epithelial cells during the secretory phase while no such
      variation was observed during the proliferative phase. The expression of
      phosphorylated Smad3 (pSmad2/3), an activated form of a component of the TGF-beta
      signalling pathway, and translocation of pSmad2/3 from the cytoplasm to the
      nucleus were more pronounced in secretory endometrium. In coculture of human
      endometrial epithelial with stromal cells, each isolated from the proliferative
      endometrium, administration of progesterone stimulated decidualization as well as
      TGF-beta signalling activation in stromal cells. Progesterone also significantly
      elevated the concentration of TGF-beta1 in the coculture medium. Careful
      manipulation of the coculture, i.e. selective addition and omission of the
      cellular components, showed that this progesterone-induced increase in secretion
      of TGF-beta1 come mainly from epithelial cells. Moreover, administration of TGF
      beta1 (10 ng/ml) directly to cultured stromal cells enhanced the expression of
      prolactin as well as pSamd2/3 even without progesterone. Taken together, our
      present data support the notion that progesterone induces stromal decidualization
      indirectly, i.e. by enhancing the expression and secretion of TGF-beta1 from
      epithelial cells. The secreted, epithelial-derived TGF-beta1 then acts on
      adjacent stromal cells, at least in part, to turn on Smad signalling that could
      lead to stromal decidualization.

PMID- 16403804
TI  - Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways
      during muscle regeneration.
AB  - Emery-Dreifuss muscular dystrophy (EDMD1) is caused by mutations in either the X
      linked gene emerin (EMD) or the autosomal lamin A/C (LMNA) gene. Here, we
      describe the derivation of mice lacking emerin in an attempt to derive a mouse
      model for EDMD1. Although mice lacking emerin show no overt pathology, muscle
      regeneration in these mice revealed defects. A bioinformatic array analysis of
      regenerating Emd null muscle revealed abnormalities in cell-cycle parameters and
      delayed myogenic differentiation, which were associated with perturbations to
      transcriptional pathways regulated by the retinoblastoma (Rb1) and MyoD genes.
      Temporal activation of MyoD transcriptional targets was significantly delayed,
      whereas targets of the Rb1/E2F transcriptional repressor complex remained
      inappropriately active. The inappropriate modulation of Rb1/MyoD transcriptional
      targets was associated with up-regulation of Rb1, MyoD and their co
      activators/repressors transcripts, suggesting a compensatory effort to overcome a
      molecular block to differentiation at the myoblast/myotube transition during
      regeneration. This compensation appeared to be effective for MyoD transcriptional
      targets, although was less effective for Rb1 targets. Analysis of Rb1
      phosphorylation states showed prolonged hyper-phosphorylation at key
      developmental stages in Emd null myogenic cells, both in vivo and in vitro. We
      also analyzed the same pathways in Lmna null muscle, which shows extensive
      dystrophy. Surprisingly, Lmna null muscle did not show the same perturbations to
      Rb- and MyoD-dependent pathways. We did observe increased transcriptional
      expression of Lap2alpha and delayed expression of Rb1, which may regulate
      alternative transcriptional pathways in the Lmna null myoblasts. We suggest that
      the dominant LMNA mutations seen in many clinically disparate laminopathies may
      similarly alter Rb function, with regard to either the timing of exit from the
      cell cycle or terminal differentiation programs or both.

PMID- 16403806
TI  - Deletion of the triplet repeat encoding polyglutamine within the mouse
      Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo
      and elevated levels of ATP with cellular senescence in vitro.
AB  - Huntingtin (htt), the protein encoded by the Huntington's disease (HD) gene,
      contains a polymorphic stretch of glutamines (polyQ) near its N-terminus. When
      the polyQ stretch is expanded beyond 37Q, HD results. However, the role of the
      normal polyQ stretch in the function of htt is still unknown. To determine the
      contribution of the polyQ stretch to normal htt function, we have generated mice
      with a precise deletion of the short CAG triplet repeat encoding 7Q in the mouse
      HD gene (Hdh(DeltaQ)). Hdh(DeltaQ/DeltaQ) mice are born with normal Mendelian
      frequency and exhibit no gross phenotypic differences in comparison to control
      littermates, suggesting that the polyQ stretch is not essential for htt's
      functions during embryonic development. Adult mice, however, commit more errors
      initially in the Barnes circular maze learning and memory test and perform
      slightly better than wild-type controls in the accelerating rotarod test for
      motor coordination. To determine whether these phenotypes may reflect an altered
      cellular physiology in the Hdh(DeltaQ) mice, we characterized the growth and
      energy status of primary embryonic and adult Hdh(DeltaQ/DeltaQ) fibroblasts in
      culture. The Hdh(DeltaQ) fibroblasts exhibited elevated levels of ATP, but
      senesced prematurely in comparison with wild-type fibroblasts. Taken altogether,
      these results suggest that htt's polyQ stretch is required for modulating
      longevity in culture and support the hypothesis that the polyQ stretch may also
      modulate a htt function involved in regulating energy homeostasis.

PMID- 16403805
TI  - The neuroprotective WldS gene regulates expression of PTTG1 and erythroid
      differentiation regulator 1-like gene in mice and human cells.
AB  - Wallerian degeneration of injured neuronal axons and synapses is blocked in
      Wld(S) mutant mice by expression of an nicotinamide mononucleotide adenylyl
      transferase 1 (Nmnat-1)/truncated-Ube4b chimeric gene. The protein product of the
      Wld(S) gene localizes to neuronal nuclei. Here we show that Wld(S) protein
      expression selectively alters mRNA levels of other genes in Wld(S) mouse
      cerebellum in vivo and following transfection of human embryonic kidney (HEK293)
      cells in vitro. The largest changes, identified by microarray analysis and
      quantitative real-time polymerase chain reaction of cerebellar mRNA, were an
      approximate 10-fold down-regulation of pituitary tumour-transforming gene-1
      (pttg1) and an approximate 5-fold up-regulation of a structural homologue of
      erythroid differentiation regulator-1 (edr1l-EST). Transfection of HEK293 cells
      with a Wld(S)-eGFP construct produced similar changes in mRNA levels for these
      and seven other genes, suggesting that regulation of gene expression by Wld(S) is
      conserved across different species, including humans. Similar modifications in
      mRNA levels were mimicked for some of the genes (including pttg1) by 1 mm
      nicotinamide adenine dinucleotide (NAD). However, expression levels of most other
      genes (including edr1l-EST) were insensitive to NAD. Pttg1(-/-) mutant mice
      showed no neuroprotective phenotype. Transfection of HEK293 cells with constructs
      comprising either full-length Nmnat-1 or the truncated Ube4b fragment (N70-Ube4b)
      demonstrated selective effects of Nmnat-1 (down-regulated pttg1) and N70-Ube4b
      (up-regulated edr1l-EST) on mRNA levels. Similar changes in pttg1 and edr1l-EST
      were observed in the mouse NSC34 motor neuron-like cell line following stable
      transfection with Wld(S). Together, the data suggest that the Wld(S) protein co
      regulates expression of a consistent subset of genes in both mouse neurons and
      human cells. Targeting Wld(S)-induced gene expression may lead to novel therapies
      for neurodegeneration induced by trauma or by disease in humans.

PMID- 16403807
TI  - Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to
      breast cancer susceptibility.
AB  - The N-terminus of the Breast Cancer-1 predisposition protein (BRCA1) associates
      with the BRCA1-associated RING domain-1 protein (BARD1) to form a heterodimer,
      which exhibits ubiquitin ligase activity that is abrogated by known cancer
      associated BRCA1 missense mutations. The majority of missense substitutions
      identified in patients with a personal or a family history of disease have not
      been followed in pedigrees, nor there is a functional understanding of their
      impact. We have examined, by extensive missense substitution, the interaction of
      BRCA1 with components that contribute to its ubiquitin ligase activity, BARD1 and
      the E2 ubiquitin-conjugating enzyme, UbcH5a. Selection from a randomly generated
      library of BRCA1 missense mutations for variants that inhibit the interaction
      with these components identified substitutions in residues found altered in
      patient DNA, indicating a correlation between loss of component-binding and
      propensity to disease development. We further show that the BRCA1:E2 interaction
      is sensitive to substitutions in all structural elements of the BRCA1 N-terminus,
      whereas the BARD1 interaction is sensitive to a subset of BRCA1 substitutions,
      which also inhibit E2-binding. Patient variants that inhibit the BRCA1:E2
      interaction show loss of ubiquitin ligase activity and correlate with disease
      susceptibility and theoretical predictions of pathogenicity. These data link the
      loss of ubiquitin ligase activity, through loss of E2-binding, to the majority of
      non-polymorphic patient variants described within the N-terminus of BRCA1 and
      illustrate the likely significant role of BRCA1 ubiquitin ligase activity in
      tumour suppression.

PMID- 16403808
TI  - Stochastic imprinting in the progeny of Dnmt3L-/- females.
AB  - The cis-acting regulatory sequences of imprinted genes are subject to germline
      specific epigenetic modifications, the imprints, so that this class of genes is
      exclusively expressed from either the paternal or maternal allele in offspring.
      How genes are differentially marked in the germlines remains largely to be
      elucidated. Although the exact nature of the mark is not fully known, DNA
      methylation [at differentially methylated regions (DMRs)] appears to be a major,
      functional component. Recent data in mice indicate that Dnmt3a, an enzyme with de
      novo DNA methyltransferase activity, and the related protein Dnmt3L are required
      for methylation of imprinted loci in germ cells. Maternal methylation imprints,
      in particular, are strictly dependent on the presence of Dnmt3L. Here, we show
      that, unexpectedly, methylation imprints can be present in some progeny of
      Dnmt3L(-/-) females. This incomplete penetrance of the effect of Dnmt3L
      deficiency in oocytes is neither embryo nor locus specific, but stochastic. We
      establish that, when it occurs, methylation is present in both embryo and extra
      embryonic tissues and results in a functional imprint. This suggests that this
      maternal methylation is inherited, directly or indirectly, from the gamete. Our
      results indicate that in the absence of Dnmt3L, factors such as Dnmt3a and
      possibly others can act alone to mark individual DMRs. However, establishment of
      appropriate maternal imprints at all loci does require a combination of all
      factors. This observation can provide a basis to understand mechanisms involved
      in some sporadic cases of imprinting-related diseases and polymorphic imprinting
      in human.

PMID- 16403809
TI  - Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological
      effects, and prediction of clinical benefits.
AB  - BACKGROUND: Bortezomib (VELCADE) is a potent inhibitor of the 26S proteasome with
      broad antitumor activity. We performed a phase II study of bortezomib to evaluate
      its clinical effects in patients with metastatic breast cancer. PATIENTS AND
      METHODS: Twelve patients with metastatic breast cancer were treated with
      bortezomib (VELCADE) at a dosage of 1.5 mg/m(2) administered biweekly for 2 weeks
      with 1 week of rest in a 21-day cycle. The primary objective was clinical
      response rate. Toxicity and pharmacodynamics data were also obtained. RESULTS: No
      objective responses were observed. One patient had stable disease, and 11 others
      experienced disease progression. The median survival time was 4.3 months (range,
      0.9-37 months). The most common grade 3 or 4 toxicities included fatigue (58%; n
      = 7) and skin rash (33%; n = 4). The mean inhibition of specific chymotryptic
      activity was 53.1% (+/- 13.33%). A statistically significant reduction in the
      plasma interleukin-6 level was seen (P = 0.0354). CONCLUSION: Bortezomib was well
      tolerated but showed limited clinical activity against metastatic breast cancer
      when used as a single agent. The future development of this agent for the
      treatment of breast cancer should be guided by in vivo models that optimize
      activity in combination with other antitumor agents.

PMID- 16403810
TI  - Occupational silica exposure and lung cancer risk: a review of epidemiological
      studies 1996-2005.
AB  - BACKGROUND: In 1997, a Monograph from the International Agency for Research on
      Cancer (IARC) classified occupational exposure to crystalline silica as
      carcinogenic to humans. Large amounts of epidemiological data have been published
      subsequently. METHODS: We conducted a systematic review of epidemiological
      investigations on silica exposure and lung cancer risk published after the IARC
      Monograph, including 28 cohort, 15 case-control and two proportionate mortality
      ratio (PMR) studies. These were identified in the available literature. RESULTS:
      The pooled RR of lung cancer, calculated using random effects models, from all
      cohort studies considering occupational exposure to silica was 1.34. The RRs were
      1.69 in cohort studies of silicotics only, 1.25 in studies where silicosis status
      was undefined and 1.19 among non silicotic subjects. The pooled RR was 1.41 for
      all case-control studies. The RRs were 3.27 in case-control studies of silicotics
      only, 1.41 in studies where silicosis status was undefined and 0.97 among non
      silicotic subjects. The RR was 1.24 for PMR studies. CONCLUSIONS: In this re
      analysis, the association with lung cancer was consistent for silicotics, but the
      data were limited for non silicotic subjects and not easily explained for
      undefined silicosis status workers. This leaves open the issue of dose-risk
      relation and pathogenic mechanisms and supports the conclusion that the
      carcinogenic role of silica per se in absence of silicosis is still unclear.

PMID- 16403811
TI  - Weekly oxaliplatin and preoperative radiotherapy as a new neoadjuvant therapy for
      locally-advanced rectal cancer.

PMID- 16403812
TI  - Survivin expression in breast cancer predicts clinical outcome and is associated
      with HER2, VEGF, urokinase plasminogen activator and PAI-1.
AB  - BACKGROUND: Survivin, a novel inhibitor of apoptosis, is one of the most cancer
      specific proteins identified to date. In this study we (a) evaluated the
      association between survivin and HER2, vascular endothelial growth factor (VEGF)
      and uPA/PAI-1 expression and (b) defined its effect on clinical outcome in a
      large breast cancer patient cohort. PATIENTS AND METHODS: Survivin expression was
      measured by ELISA in primary breast cancer tissue extracts from 420 patients with
      long-term clinical follow-up. RESULTS: Survivin was detected in 378 (90%) of the
      420 primary breast cancer cases. Increased survivin levels were significantly
      associated with high nuclear grade (P < 0.0001), negative hormone receptor status
      (P = 0.0028), HER2 overexpression (P = 0.0094), VEGF expression (P < 0.0001),
      high uPA (P = 0.0002) and PAI-1 levels (P = 0.0002). Using the 25th percentile
      (1.4 ng/mg) as a cut-off point, patients expressing elevated survivin had a
      significantly worse disease-free survival (DFS: P = 0.0007, RR 1.97) and overall
      survival (OS: P = 0.0009, RR 2.11) compared with patients expressing lower levels
      of survivin. In multivariate analysis, this prognostic value of survivin was
      independent of both traditional and novel clinicopathologic factors for both DFS
      (P = 0.0076, RR 1.72) and OS (P = 0.0155, RR 1.76). CONCLUSIONS: The independent
      prognostic relevance of survivin, when combined with previous data from model
      systems implicating survivin in the inhibition of apoptosis, suggests that
      survivin may be a suitable target for future therapeutic strategies.

PMID- 16403813
TI  - Prediction of response to imatinib by prospective quantitation of BCR-ABL
      transcript in late chronic phase chronic myeloid leukemia patients.
AB  - Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent
      antileukemic activity in clinical studies of chronic myeloid leukemia (CML)
      patients. Early prediction of response to imatinib cannot be anticipated. We used
      a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT
      PCR) for BCR-ABL transcripts on 191 out of 200 late-chronic phase CML patients
      enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow
      samples were collected before treatment, after 12, 20 and at the end of study
      treatment (52 weeks) while peripheral blood samples were obtained after 2, 3, 6,
      10, 14, 20 and 52 weeks of therapy. The amount of BCR-ABL transcript was
      expressed as the ratio of BCR-ABL to beta2-microglobulin (beta2M). We show that,
      following initiation of imatinib, the early BCR-ABL level trends in both bone
      marrow and peripheral blood samples made it possible to predict the subsequent
      cytogenetic outcome and response. We propose this method as the method of choice
      for monitoring patients on imatinib therapy. QRT-PCR studies may be able to
      identify degrees of molecular response that predict both complete cytogenetic
      response and long term stability, as well as patterns of response that provide an
      early indication of relapse and imatinib resistance.

PMID- 16403814
TI  - Decreased androgen receptor gene methylation in premature pubarche: a novel
      pathogenetic mechanism?
AB  - CONTEXT: Several studies found links between DNA methylation and gene expression.
      In patients with idiopathic hirsutism, a preferential methylation of the of
      shorter androgen receptor (AR) alleles was hypothesized to be responsible for the
      abnormal hair growth. OBJECTIVE: The objective of this study was to assess
      whether abnormalities in the AR function in both peripheral blood leukocytes
      (PBLs) and androgen target tissues are present in children with premature
      pubarche (PP). DESIGN: Human DNA was extracted from PBLs and pubic hair and CAG
      repeats length and methylation status of the AR gene were analyzed. SETTING: The
      study was performed at a Pediatric Endocrinology referral clinic. PATIENTS:
      Twenty-five girls with PP, 23 prepubertal children, and 10 girls with Tanner
      stage II pubertal development were studied. MAIN OUTCOME MEASURE: The main
      outcome measures were CAG repeat length and AR methylation pattern in PBLs and
      pubic hair. RESULTS: In PBLs from PP patients, AR gene methylation was
      significantly lower (P < 0.01) than that of prepubertal children and similar to
      that of girls with Tanner II stage pubertal development. A negative correlation
      between AR gene methylation in PBLs and the age of normal children was detected.
      PATIENTS with PP exhibited a hair follicle AR methylation pattern similar to that
      of Tanner stage II girls. The mean number of CAG repeats was lower in PP patients
      than in prepubertal and Tanner stage II girls, although it was within the normal
      range for the general population in both groups. CONCLUSIONS: The increased AR
      gene activity observed in PP patients, as indicated by the reduced AR gene
      methylation pattern, together with the presence of shorter CAG repeats, might
      lead to hypersensitivity of the hair follicles to steroid hormones and therefore
      to the premature development of pubic hair.

PMID- 16403815
TI  - Clinical case seminar: metastatic follicular thyroid carcinoma arising from
      congenital goiter as a result of a novel splice donor site mutation in the
      thyroglobulin gene.
AB  - CONTEXT: Defects in thyroglobulin (Tg) synthesis are one of the causes of thyroid
      dyshormonogenesis. Only a few mutations in the Tg gene have been described.
      OBJECTIVES: We describe a novel Tg gene mutation and discuss the mechanisms by
      which it causes dyshormonogenesis with subsequent malignant transformation.
      CASES: Two siblings aged 21 and 19 yr presented with recurrent goiters for which
      they had undergone multiple thyroid surgeries since early childhood. The older
      sibling was diagnosed with metastatic follicular thyroid carcinoma at age 15 yr.
      METHODS: The entire coding region and intron-exon boundaries of the Tg gene were
      amplified and sequenced from the patients. We also sequenced the boundaries of
      exon 5 and intron 5 from both parents. RT-PCR amplification of a cDNA fragment
      encompassing exons 4-6 was also performed. RESULTS: A homozygous G to A point
      mutation at position +1 of the splice donor site of intron 5 (g.IVS5+1G-->A) was
      detected in both patients, whereas a monoallelic mutation was found in their
      parents. RT-PCR amplification of a cDNA fragment covering exons 4-6 revealed a
      191-bp fragment in the patients and 351- and 191-bp fragments in the parents.
      Sequence analysis of these two fragments confirmed deletion of exon 5 in the 191
      bp fragment. CONCLUSIONS: Aberrant splicing occurred as a result of the g.IVS5+1G
      ->A mutation, which caused fusion of exons 4 and 6, resulting in the frame shift
      at codon position 141 and a premature stop codon at position 147 (FS141-->147X).
      The malignant transformation is likely a result of prolonged TSH stimulation.

PMID- 16403816
TI  - [11C]metomidate positron emission tomography of adrenocortical tumors in
      correlation with histopathological findings.
AB  - CONTEXT: Adrenal incidentalomas are common findings necessitating extensive
      laboratory work-up and repetitive radiological examinations. Positron emission
      tomography (PET) using (11)C-labeled metomidate (MTO) has previously been
      described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated
      212 MTO-PET examinations in 173 patients to identify its role in the management
      of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73
      patients were retrospectively analyzed. SETTING: All examinations were performed
      at a referral center. PATIENTS: Patients who were operated or biopsied due to
      adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n =
      26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8),
      pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n
      = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses
      and findings while scrutinizing images. The hypothesis that MTO-PET is of value
      in the management of adrenal tumors, especially incidentaloma, was stated before
      data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO
      PET in proving adrenocortical origin of the lesions. Pheochromocytomas,
      metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET
      measurements using standardized uptake values (SUV) in pathological
      adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from
      normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting
      adenomas, and the SUV ratio between the tumor and the contralateral gland was
      significantly higher in all hormonally hypersecreting adenomas as well as in ACC.
      CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing
      adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal
      incidentalomas and may be beneficial for the examination of patients with primary
      aldosteronism or ACC.

PMID- 16403817
TI  - Tumor necrosis factor alpha and glucocorticoid synergistically increase leptin
      production in human adipose tissue: role for p38 mitogen-activated protein
      kinase.
AB  - CONTEXT: TNF increases plasma leptin in humans in vivo, but previous studies
      showed it decreases leptin in vitro. OBJECTIVE AND PARTICIPANTS: The objective of
      this study was to determine the effect of TNF on leptin release from human
      adipose tissue (AT) from healthy subjects undergoing elective surgery or needle
      aspirations of AT at a university hospital. DESIGN: Human omental and abdominal
      sc AT fragments from non- obese and obese subjects were placed in organ culture
      without or with TNF added in the presence or absence of insulin and/or
      dexamethasone (dex; a synthetic glucocorticoid) for up to 2 d. RESULTS: In the
      absence of hormones, culture with TNF decreased leptin release. In contrast, when
      added in the presence of dex, TNF increased secreted leptin and leptin mRNA
      abundance in AT from nonobese and obese subjects. The TNF + dex-stimulated
      increase in leptin was associated with an increase in p38 MAPK activity and was
      totally blocked by p38 MAPK inhibitors. In contrast, inhibition of p38 MAPK only
      partially blocked the effect of TNF on IL-6 production. Culture of obese AT with
      either p38 or p44/42 MAPK inhibitors also blunted the spontaneous increase in
      media leptin that occurred from d 1-2 of culture in omental AT of obese subjects.
      CONCLUSION: Synergistic effects of increased local or systemic TNF in combination
      with glucocorticoids may contribute to increased leptin expression in response to
      stress, including infection and obesity.

PMID- 16403818
TI  - Hormone predictors of bone mineral density changes during the menopausal
      transition.
AB  - OBJECTIVE AND CONTEXT: Our objective was to examine predictability of
      reproductive hormone concentrations for bone mineral density (BMD) loss during
      the menopausal transition. DESIGN: We conducted a longitudinal (five annual
      examinations), multiple-site (n = 5) cohort study, the Study of Women's Health
      Across the Nation (SWAN). PARTICIPANTS: Participants included, at baseline, 2311
      premenopausal or early perimenopausal African-American, Caucasian, Chinese, and
      Japanese women. MAIN OUTCOME MEASURES: We assessed annual dual-energy x-ray
      absorptiometry lumbar spine and total hip BMD measures, with endogenous estradiol
      (E2), FSH, androgens, and self-reported menstrual bleeding patterns. RESULTS:
      Over the 4-yr period, lumbar spine BMD loss was 5.6% in natural postmenopause,
      3.9% in surgical postmenopause, or 3.2% in late perimenopause. Baseline FSH
      concentrations, subsequent FSH levels, and their interaction predicted 4-yr BMD
      loss. If baseline FSH was less than 25 mIU/ml, higher follow-up FSH (>70 mIU/ml)
      predicted a 4-yr spine BMD loss of -0.05 g/cm(2). If baseline FSH values were
      more than 35-45 mIU/ml, lower follow-up FSH (i.e. 40-50 mIU/ml) predicted a -0.05
      g/cm(2) 4-yr spine BMD loss. Charts show amounts of predicted BMD losses with
      combinations of baseline FSH values and FSH levels over time. E2 concentrations
      less than 35 pg/ml were associated with lower BMD, but annual E2 measures and
      changes did not predict BMD loss. Testosterone, free androgen index, and
      dehydroepiandrosterone sulfate concentrations were not significantly associated
      with BMD loss. CONCLUSIONS: Spine and hip BMD losses during the menopause
      transition were most strongly related to the interaction between initial FSH
      levels and longitudinal FSH changes and not to E2 or androgen levels or changes.

PMID- 16403819
TI  - Congenital hyperinsulinism: pancreatic [18F]fluoro-L-dihydroxyphenylalanine
      (DOPA) positron emission tomography and immunohistochemistry study of DOPA
      decarboxylase and insulin secretion.
AB  - CONTEXT: Congenital hyperinsulinism (HI) is characterized by hypoglycemia related
      to inappropriate insulin secretion. Focal and diffuse forms of hyperinsulinism
      share a similar clinical presentation, but their treatment is dramatically
      different. Preoperative differential diagnosis was based on pancreatic venous
      sampling, a technically demanding technique. OBJECTIVE: Positron emission
      tomography (PET) after injection of [18F]fluoro-L-DOPA (L-dihydroxyphenylalanine)
      has been evaluated for the preoperative differentiation between focal and diffuse
      HI, by imaging uptake of radiotracer and the conversion of [18F]fluoro-L-dopa
      into dopamine by DOPA decarboxylase. We propose to validate this test by
      immunohistochemical approach. PATIENTS AND METHODS: Pancreatic surgical specimens
      of four focal and three diffuse HI were studied, using anti-DOPA decarboxylase
      and proinsulin antibodies. The effect of an inhibitor of DOPA decarboxylase
      (carbidopa) on insulin secretion was evaluated in vivo and in cultured INS-1
      cells. RESULTS: Immunohistochemical detection of DOPA decarboxylase showed
      diffuse staining of Langerhans islets in the whole pancreas in all diffuse cases,
      in contrast with dense focal staining in all focal cases. Staining of Langerhans
      islets outside the focal lesion was diffusely but weakly positive. We correlated
      the localization of DOPA decarboxylase and proinsulin in normal pancreas and in
      both diffuse and focal HI tissues. The diffuse PET uptake found before treatment
      in one child with diffuse HI disappeared completely after carbidopa
      administration, suggesting in vivo that pancreatic cells can take up amine
      precursors and contain DOPA decarboxylase. The insulin secretion measured in the
      supernatant was the same whether INS-1 cells were treated by dopamine or Lodosyn
      or untreated. CONCLUSION: We validate PET with as a consistent test to
      differentiate diffuse and focal HI.

PMID- 16403820
TI  - Clinical review: Type 1 diabetes-associated autoimmunity: natural history,
      genetic associations, and screening.
AB  - CONTEXT: Type 1 diabetes (T1D) is associated with autoimmune thyroid disease
      (AIT), celiac disease (CD), Addison's disease (AD), and other autoimmune
      diseases. These diseases can occur together in defined syndromes with distinct
      pathophysiology and characteristics: autoimmune polyendocrine syndrome I,
      autoimmune polyendocrine syndrome II, and the immunodysregulation
      polyendocrinopathy enteropathy X-linked syndrome. EVIDENCE ACQUISITION: Review of
      the medical literature was performed with particular attention to the natural
      history, genetic factors, and syndromes associated with T1D, AIT, CD, and AD.
      EVIDENCE SYNTHESIS: Genetic risk for these diseases overlaps and includes genes
      within the major histocompatibility complex (MHC) such as the human leukocyte
      antigens (HLA) DR and DQ alleles and the MHC I-related gene A (MIC-A). Other
      genes outside of the MHC have been associated with these autoimmune diseases,
      including the gene encoding the lymphoid tyrosine phosphatase (PTPN22) and the
      cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene. CONCLUSION: Genetic
      risk for T1D overlaps with AIT, CD, and AD. Disease risk is associated with organ
      specific autoantibodies, which can be used to screen subjects with T1D.

PMID- 16403821
TI  - The structural brain correlates of cognitive deficits in adults with
      Klinefelter's syndrome.
AB  - CONTEXT: Adults with Klinefelter's syndrome (KS) are known to present
      disturbances of language skills and delayed learning abilities. OBJECTIVES: The
      aim of this study was to assess brain morphometry in KS and to correlate eventual
      volumetric changes with performance on neuropsychological tests. PATIENTS:
      Patients included 18 KS adults and 20 age-matched controls. METHODS: All
      participants underwent prospectively double-spin-echo brain magnetic resonance
      imaging and neuropsychological testing of verbal and nonverbal domains. On the
      axial stack of magnetic resonance imaging slices, regional brain volumes were
      measured either by automated segmentation (full brain, total cerebrospinal fluid,
      and ventricular volume) or manual drawing with help of a neuroanatomy atlas
      (frontal, temporal, and parietal lobes, gray matter component of the lobes,
      cerebellar hemispheres, and hippocampal complexes). RESULTS: KS patients
      performed significantly lower than controls on language-related tasks exploring
      verbal processing speed and verbal executive function. They were diagnosed with
      significant enlargement of ventricular volume and bilateral reduction of
      cerebellar hemispheres. Furthermore, after separation of participants according
      to handedness and after correction of regional brain volumes for atrophy, a
      significant reduction of left temporal lobe volume was found in KS compared with
      controls. Ventricular volume was inversely correlated with cognitive function,
      whereas left temporal lobe volume was positively correlated with language-related
      tasks. CONCLUSION: This study hypothesizes that supernumerary X-chromosome and/or
      congenital hypogonadism provoke structural alterations in the subcortical
      pathways involved in language processing, thus providing a neurobiological
      substrate for cognitive deficits in KS.

PMID- 16403822
TI  - Pharmacokinetic studies of recombinant human insulin-like growth factor I (rhIGF
      I)/rhIGF-binding protein-3 complex administered to patients with growth hormone
      insensitivity syndrome.
AB  - CONTEXT: GH insensitivity syndrome (GHIS), Laron syndrome, is characterized by
      severe short stature, high serum GH levels, and very low serum IGF-I and IGF
      binding protein-3 (IGFBP-3) levels associated with a genetic defect of the GH
      receptor. Recombinant human (rh) IGF-I treatment at doses of 80-120 microg/kg
      given sc twice daily is effective in promoting growth in these patients. We have
      investigated a newly developed drug, rhIGF-I/rhIGFBP-3, a 1:1 molar complex of
      rhIGF-I and rhIGFBP-3. OBJECTIVES: The objectives of the study were to determine
      IGF-I pharmacokinetics after the administration of rhIGF-I/rhIGFBP-3 in
      adolescents with GHIS and to evaluate its safety and tolerability. DESIGN: This
      was an open-label clinical study. SETTING: The study was conducted in a general
      pediatric ward of a university teaching hospital. PARTICIPANTS: Four patients
      (one female and three males; mean age, 14.9 yr; mean height sd score, -4.9) with
      confirmed molecular diagnosis of GHIS agreed to participate in the study.
      INTERVENTION: rhIGF-I/rhIGFBP-3 was administered in a single sc injection at 0.5
      and 1.0 mg/kg.dose (equivalent to 100 and 200 microg/kg rhIGF-I) after breakfast
      with a 2-d interval between doses. RESULTS: IGF-I levels reached a maximum
      between 19 +/- 8.3 and 15 +/- 6.2 h for the low and high doses, respectively. The
      circulating IGF-I levels obtained with the low and high doses were similar,
      although a discrete dose-dependent increase in circulating IGF-I levels was
      observed. The IGF-I half-life in four subjects after a dose of 0.5 mg/kg rhIGF
      I/rhIGFBP-3 was estimated to be 21+/- 4 h. There were no acute adverse events
      reported, and all blood glucose measurements were normal. CONCLUSION: These data
      demonstrated that the rhIGF-I/rhIGFBP-3 complex was effective in increasing
      levels of circulating total and free IGF-I into the normal range for a 24-h
      period after a single sc administration in patients with GHIS, and that
      administration of rhIGF-I/rhIGFBP-3 was safe and well tolerated.

PMID- 16403824
TI  - Conventional pituitary irradiation is effective in lowering serum growth hormone
      and insulin-like growth factor-I in patients with acromegaly.
AB  - BACKGROUND: There has been recent controversy as to the effectiveness of
      conventional pituitary irradiation in reducing circulating GH levels to less than
      2.5 ng/ml and/or normalization of serum IGF-I. OBJECTIVES: Our objectives were to
      determine the effects of conventional pituitary irradiation on 1) lowering of
      serum GH and IGF-I levels, 2) the proportion of patients who achieve a GH level
      less than 2.5 ng/ml and a normal age-corrected IGF-I and the time taken to
      achieve this, and 3) the incidence of hypopituitarism and other adverse effects.
      DESIGN: We conducted retrospective data collection from 14 centers throughout the
      United Kingdom. PATIENTS: We studied 1840 patients with acromegaly, of whom 884
      had received conventional pituitary irradiation. MEASUREMENTS: We assessed
      circulating GH and IGF-I levels and pituitary function at intervals after
      irradiation. RESULTS: Mean GH levels declined from 13.5 to 5.3 ng/ml at 2 yr
      after irradiation, to 2.0 ng/ml by 10 yr, and to 1.1 ng/ml at 20 yr. Twenty-two
      percent of patients achieved a level less than 2.5 ng/ml by 2 yr, 60% by 10 yr,
      and 77% by 20 yr. The interval to achieve this depended on the preirradiation GH
      level. IGF-I levels fell in parallel to those of GH with 63% of patients having a
      normal level by 10 yr. The proportions of patients with new pituitary hormone
      deficiencies 10 yr after irradiation were 18% for LH/FSH, 15% for ACTH, and 27%
      for TSH. No other side effects were noted. CONCLUSIONS: In this, the largest
      series reported, conventional pituitary irradiation is shown to be an effective
      and safe means of reducing both serum GH and IGF-I concentrations in patients
      with acromegaly.

PMID- 16403823
TI  - Improvement of cardiac performance and cardiovascular risk factors in children
      with GH deficiency after two years of GH replacement therapy: an observational,
      open, prospective, case-control study.
AB  - CONTEXT: GH deficiency (GHD) in adults is associated with a cluster of
      cardiovascular risk factors that may contribute to an increased mortality for
      cardiovascular disease. OBJECTIVE: The aim of this study was to evaluate the
      effect of GHD and GH replacement therapy on cardiac performance, lipid profile,
      and insulin resistance in children. DESIGN: This was a 2-yr case-control
      prospective study. PATIENTS: Thirty children with GHD aged 9.3 +/- 0.5 yr and 30
      healthy matched controls were studied. INTERVENTION: Children were studied before
      and after 1 and 2 yr of GH replacement (GHD children) or no treatment (controls).
      MAIN OUTCOME MEASURES: Lipid profile, serum insulin levels, homeostasis model of
      assessment (HOMA) index, and left ventricular (LV) mass and function by
      echocardiography were the main outcome measures. RESULTS: At study entry, the LV
      mass index was significantly lower in GHD children (50.2 +/- 1.7) than in
      controls (60.3 +/- 2.5 g/m(2); P < 0.002), whereas LV systolic and diastolic
      function, lipid profile, insulin levels, and HOMA index were similar. In GHD
      children LV mass index significantly increased (66.3 +/- 2.4 g/m(2); P < 0.0001)
      after 1 yr of GH replacement and remained stable thereafter. LV systolic and
      diastolic function did not change during treatment. After 2 yr of GH replacement,
      total cholesterol (P < 0.007) and the atherogenic index (P < 0.0001)
      significantly decreased, whereas fasting insulin levels (P < 0.001) and HOMA
      index (P < 0.0001) significantly increased compared with both pretreatment and
      control values. CONCLUSIONS: GHD in children is associated with a reduced cardiac
      size but with a normal cardiac function, lipid profile, and insulin sensitivity.
      Two years of GH replacement normalizes cardiac morphology, improves lipid
      profile, and slightly impairs insulin sensitivity.

PMID- 16403825
TI  - An empirical approach for detecting nucleotide-binding sites on proteins.
AB  - Protein structure data in the PDB (Protein Data Bank) were used to construct
      empirical scores of nucleotide-protein interactions. A simple strategy to
      evaluate the spatial distribution of protein atoms around the base moieties of
      nucleotides was applied to categorize adenine, guanine, nicotinamide and flavin
      nucleotide-binding sites. In addition to the known nucleotide-binding motifs, the
      empirical scores detected several other features that were shared among proteins
      with different folds. The empirical scores were also used to predict the binding
      sites on protein molecules and a comprehensive test of the prediction system was
      performed. As a result, adenine, guanine, nicotinamide and flavin sites were
      detected with efficiencies of 31, 29, 32 and 40%, respectively. The predictions
      were judged to be successful if the predicted base with the best score was
      located within a 3.0 A r.m.s.d. from the known ligand positions.

PMID- 16403826
TI  - Clinical and subclinical inflammation in patients with familial Mediterranean
      fever and in heterozygous carriers of MEFV mutations.
AB  - OBJECTIVE: To prospectively monitor inflammatory activity over a prolonged period
      in a cohort of Turkish patients with FMF, their healthy relatives and healthy
      controls and to relate this to their MEFV genotypes. METHODS: 43 patients with
      FMF and 75 of their asymptomatic relatives underwent fortnightly assessments and
      venesection for measurement of CRP and SAA over 5 months. 50 unrelated healthy
      population matched controls were also studied. MEFV genotyping was performed on
      all participants and comparisons were made between the different groups. RESULTS:
      Paired MEFV mutations were detected in 84% of FMF patients and single mutations
      in 12%. Substantial acute phase reactivity was seen among the patients with FMF
      during attacks (median SAA 693 mg/l, CRP 115 mg/l). Between attacks there was
      also some inflammatory activity (median SAA 6 mg/l, CRP 4 mg/l). Among healthy
      controls 16% were heterozygotes for MEFV mutations and 4% had two mutations. As
      expected there was a substantial carrier rate among healthy relatives with
      mutations detected in almost 92%. Asymptomatic MEFV heterozygotes had elevated
      acute phase proteins compared to wild type subjects. CONCLUSION: Substantial sub
      clinical inflammation occurs widely and over prolonged periods in patients with
      FMF, indicating that the relatively infrequent clinically overt attacks represent
      the 'tip of the iceberg' in this disorder. Both basal and peak acute phase
      protein concentrations were greater in MEFV heterozygotes than in wild-type
      controls, regardless of mutation demonstrating a 'pro-inflammatory' phenotype
      among FMF carriers. Upregulation of the acute phase response among carriers of
      FMF may augment their innate host response and contribute to better resistance to
      infection.

PMID- 16403827
TI  - Takayasu's arteritis: a cause of prolonged arterial stiffness.
AB  - OBJECTIVES: Cardiovascular disease is a major cause of mortality and morbidity in
      patients with Takayasu's arteritis (TA). Increased arterial stiffness is an
      independent risk factor and predictor of cardiovascular mortality in a variety of
      diseases. Pulse wave velocity (PWV) and the augmentation index (AI) are used as
      clinical measurements of arterial stiffness. METHODS: Data are presented from 10
      patients with TA and 11 normal controls obtained between 2000 and 2004. Arterial
      compliance was assessed non-invasively by measurement of PWV, using the Complior
      system, and calculation of the aortic AI. RESULTS: TA patients (mean age 40.8+/
      13.2 yr) were compared with a control group of healthy women from a parallel
      study (mean age 32.3+/-5.5 yr). The mean carotid-femoral PWV (PWV-CF) was higher
      in TA patients (P = 0.03). In addition, both aortic AI derived from the radial
      artery (P = 0.002) and carotid AI (P = 0.03) were higher in TA patients compared
      with controls. PWV-CF did not correlate with CRP (r = - 0.23, P = 0.23) or ESR (r
      = - 0.19, P = 0.27). Similar results were obtained for the correlation of carotid
      radial PWV with CRP (r = 0.15, P = 0.32) and ESR (r = 0.33, P = 0.14).
      CONCLUSIONS: Our data show that TA is associated with elevated arterial stiffness
      in the central aorta, which may persist when the disease is quiescent. These data
      suggest that PWV represents a means by which cardiovascular risk can be detected
      and monitored in TA, and highlights the importance of effective management of
      cardiovascular risk factors in these patients.

PMID- 16403828
TI  - Two familial cases of antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis.

PMID- 16403829
TI  - The effects of tobacco smoking and rheumatoid factor seropositivity on disease
      activity and joint damage in early rheumatoid arthritis.
AB  - OBJECTIVE: To study the effect of tobacco smoking and rheumatoid factor (RF)
      isotypes on disease activity and joint damage in early rheumatoid arthritis (RA).
      METHODS: One hundred early RA patients were followed prospectively for 2 yr. They
      were evaluated at recruitment and at 6 and 24 months. Sociodemographic
      information included smoking history, and radiographs of hands and feet were
      obtained. RF was monitored by IgM- and IgA-specific RF enzyme-linked
      immunosorbent assay and by agglutination, and serial measurements were also
      obtained for C-reactive protein. The influence of tobacco smoking and RF
      positivity on disease outcome was evaluated using multivariate analysis.
      Covariates for the regression analysis included sex, age, coffee consumption and
      IgA-RF positivity. RESULTS: A gradient of increase in disease activity was
      observed from never smokers to former smokers to current smokers during the 2 yr
      of observation, defined by number of swollen joints (SJC), tender joints (TJC)
      and visual analogue scale for pain (P<0.001, P=0.02 and P=0.005, respectively),
      but smoking status did not influence radiological progression. Ever smokers were
      more often IgA RF positive (P<0.05). IgA RF-positive patients had more active
      disease (SJC P=0.002, TJC P=0.01) and showed more radiological progression
      (P<0.0001) compared with IgA RF-negative patients. Of the RF-positive patients
      22% had elevated IgM RF without IgA RF and these patients showed similar disease
      activity and radiological joint progression to the RF-negative patients. None of
      these associations were explained by possible confounders. CONCLUSION: Tobacco
      smoking has an adverse effect on patients with early RA and this is possibly
      immunologically mediated. IgM RF does not predict poorer prognosis in RA unless
      it is associated with a concomitant elevation of IgA RF.

PMID- 16403830
TI  - In SAPHO syndrome anti-TNF-alpha therapy may induce persistent amelioration of
      osteoarticular complaints, but may exacerbate cutaneous manifestations.
AB  - OBJECTIVES: SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and
      osteitis) is a rare disease combining skin, bone and joint manifestations. In
      recent years new therapeutic strategies have been tried, among them TNF-alpha
      blocking agents. We report our experience with infliximab in four cases of SAPHO
      syndrome refractory to conventional therapies. METHODS: Between 2002 and 2005,
      four cases of SAPHO syndrome (two females and two males; mean age 49.7 yr)
      responding poorly to conventional drugs were treated with infliximab. The dose
      was 5 mg/kg, according to the protocol used in spondyloarthropathies, with
      infusions at 0, 2 and 6 weeks followed by 6 weeks intervals. No active cutaneous
      manifestations were present at the time of starting therapy. RESULTS: Complete
      remission of osteoarticular involvement was achieved after the second or third
      infusion, and the positive response was maintained for up to 12 months. A patient
      relapsed after discontinuation of infliximab, because of infectious complication.
      Palmoplantaris pustulosis relapsed in two patients after three and six infusions,
      respectively; there was slight improvement after discontinuation of anti-TNF
      alpha drugs. CONCLUSIONS: Infliximab seems to be a very effective therapy for
      osteoarticular complaints of SAPHO syndrome. Cutaneous involvement responded less
      favourably, palmoplantaris pustulosis relapse being a possible complication.

PMID- 16403831
TI  - Increased expression but not targeting of ENaC in adrenalectomized rats with PAN
      induced nephrotic syndrome.
AB  - Sodium retention is a hallmark of nephrotic syndrome (NS). Puromycin
      aminonucleoside (PAN)-induced NS is associated with high aldosterone levels and
      increased ENaC expression and apical targeting. However, the mechanisms
      associated with increased apical targeting of ENaC in NS remain undefined, and it
      is unclear whether this is secondary to high aldosterone levels and whether
      aldosterone and/or apical ENaC targeting are important for the development of
      sodium retention. This study aimed at uncovering 1) whether aldosterone is
      essential for sodium retention in PAN-induced NS, 2) whether ENaC expression or
      apical targeting is secondary to high aldosterone levels, and 3) the role of
      aldosterone in the dysregulation of sodium transporters in NS. Puromycin
      treatment of adrenalectomized (ADX) rats supplemented with dexamethasone induced
      sodium retention despite the absence of aldosterone. Immunocytochemical analyses
      revealed an absence of enhanced apical targeting of ENaC subunits in PAN-treated
      ADX (ADX-PAN) rats, with distribution of labeling similar to adrenalectomized
      dexamethasone-treated control rats (ADX). Moreover, ENaC subunit abundance was
      increased in ADX-PAN rats. The abundance of aquaporin-2 was unchanged, whereas
      apical targeting was enhanced. Key sodium transporters were downregulated as
      previously observed in nonadrenalectomized puromycin-treated rats (Kim SW, Wang
      W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frokiaer J, and Nielsen S. Am J
      Physiol Renal Physiol 286: F922-F935, 2004), whereas the global expression of the
      alpha1-subunit of the Na-K-ATPase was unchanged. In conclusion, PAN treatment in
      the absence of aldosterone induced sodium retention, increased ENaC expression,
      but did not change the subcellular distribution of ENaC. This indicates that the
      previously observed enhanced apical targeting of ENaC in PAN-induced NS (Kim SW,
      Wang W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frokiaer J, and Nielsen S.
      Am J Physiol Renal Physiol 286: F922-F935, 2004) is caused by aldosterone and
      that development of sodium retention can occur in the absence of aldosterone in
      NS.

PMID- 16403832
TI  - Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical
      and chemical stimuli: an afferent origin of pelvic organ cross-sensitization.
AB  - Chronic pelvic pain (CPP) disorders frequently overlap. We have demonstrated that
      acute and chronic colonic irritation can lead to neurogenic cystitis. We
      hypothesize that acute colonic irritation can sensitize urinary bladder afferents
      to mechanical and chemical stimuli. Single-unit afferent activity was recorded
      from fine filaments of the pelvic nerve in urethane-anesthetized Sprague-Dawley
      female rats before and 1 h after intracolonic administration of
      trinitrobenzenesulfonic acid (TNBS). Only spontaneously active afferents with
      receptive fields in the bladder and conduction velocities <2.5 m/s (unmyelinated
      C-fibers) were studied. Mechanical sensitivity was tested by bladder distension
      (BD) during saline infusion, whereas chemical sensitivity was tested with
      intravesical capsaicin, bradykinin, or substance P. Colonic irritation increased
      the resting firing rate of bladder afferents twofold (1.0 +/- 0.2 vs. 0.49 +/-
      0.2 impulses/s, P < 0.05). Moreover, at low-pressure BDs (10-20 mmHg), a greater
      percentage of afferents exhibited increased activity following TNBS (73 vs. 27%,
      P < 0.05). Although the magnitude of the afferent response to BD was unchanged at
      low pressures, the response was greatly enhanced at pressures 30 mmHg and above
      (2.36 +/- 0.56 vs. 8.55 +/- 0.73 impulses/s, P < 0.05). Responses to capsaicin,
      bradykinin, and substance P were also significantly enhanced following TNBS, and
      all responses were blocked by bladder denervation. In rats, colonic irritation
      sensitizes urinary bladder afferents to noxious mechanical and chemical stimuli.
      Interruption of the neural input to the bladder minimized this effect, suggesting
      a local afferent pathway from the colon. Thus, the overlap of CPP disorders may
      be a consequence of pelvic afferent cross-sensitization.

PMID- 16403833
TI  - WNK kinases influence TRPV4 channel function and localization.
AB  - TRPV4, a renally expressed nonselective cation channel of the transient receptor
      potential (TRP) family, is gated by hypotonicity. Kinases of the WNK family
      influence expression and function of the thiazide-sensitive Na+-Cl-
      cotransporter, and monogenic human hypertension has been linked to mutations in
      the gene coding for WNK4. Along with TRPV4, WNK isoforms are highly expressed in
      the distal nephron. We show here that coexpression of WNK4 downregulates TRPV4
      function in human embryonic kidney (HEK-293) cells and that this effect is
      mediated via decreased cell surface expression of TRPV4; total abundance of TRPV4
      in whole cell lysates is unaffected. The effect of the related kinase WNK1 on
      TRPV4 function and surface expression was similar to that of WNK4. Disease
      causing point mutations in WNK4 abrogate, but do not eliminate, the inhibitory
      effect on TRPV4 function. In contrast to wild-type WNK4, a kinase-dead WNK4 point
      mutant failed to influence TRPV4 trafficking; however, deletion of the entire
      WNK4 kinase domain did not blunt the effect of WNK4 on localization of TRPV4.
      Deletion of the extreme COOH-terminal putative coiled-coil domain of WNK4
      abolished its effect. In immunoprecipitation experiments, we were unable to
      detect direct interaction between TRPV4 and either WNK kinase. In aggregate,
      these data indicate that TRPV4 is functionally regulated by WNK family kinases at
      the level of cell surface expression. Because TRPV4 and WNK kinases are
      coexpressed in the distal nephron in vivo and because there is a tendency toward
      hypercalcemia in TRPV4-/- mice, we speculate that this pathway may impact
      systemic Ca2+ balance. In addition, because WNK kinases and TRPV4 are activated
      by anisotonicity, they may comprise elements of an osmosensing or osmotically
      responsive signal transduction cascade in the distal nephron.

PMID- 16403834
TI  - Differential expression of nuclear AT1 receptors and angiotensin II within the
      kidney of the male congenic mRen2. Lewis rat.
AB  - We established a new congenic model of hypertension, the mRen(2). Lewis rat and
      assessed the intracellular expression of angiotensin peptides and receptors in
      the kidney. The congenic strain was established from the backcross of the
      (mRen2)27 transgenic rat that expresses the mouse renin 2 gene onto the Lewis
      strain. The 20-wk-old male congenic rats were markedly hypertensive compared with
      the Lewis controls (systolic blood pressure: 195 +/- 2 vs. 107 +/- 2 mmHg, P <
      0.01). Although plasma ANG II levels were not different between strains,
      circulating levels of ANG-(1-7) were 270% higher and ANG I concentrations were
      40% lower in the mRen2. Lewis rats. In contrast, both cortical (CORT) and
      medullary (MED) ANG II concentrations were 60% higher in the mRen2. Lewis rats,
      whereas tissue ANG I was 66 and 84% lower in CORT and MED. For both strains, MED
      ANG II, ANG I, and ANG-(1-7) were significantly higher than CORT levels.
      Intracellular ANG II binding distinguished nuclear (NUC) and plasma membrane (PM)
      receptor using the ANG II radioligand 125I-sarthran. Isolated CORT nuclei
      exhibited a high density (Bmax >200 fmol/mg protein) and affinity for the
      sarthran ligand (KD<0.5 nM); the majority of these sites (>95%) were the AT1
      receptor subtype. CORT ANG II receptor Bmax and KD values in nuclei were 75 and
      50% lower, respectively, for the mRen2. Lewis vs. the Lewis rats. In the MED, the
      PM receptor density (Lewis: 50 +/- 4 vs. mRen2. Lewis: 21 +/- 5 fmol/mg protein)
      and affinity (Lewis: 0.31 +/- 0.1 vs. 0.69 +/- 0.1 nM) were lower in the mRen2.
      Lewis rats. In summary, the hypertensive mRen2. Lewis rats exhibit higher ANG II
      in both CORT and MED regions of the kidney. Evaluation of intracellular ANG II
      receptors revealed lower CORT NUC and MED PM AT1 sites in the mRen2. Lewis. The
      downregulation of AT1 sites in the mRen2. Lewis rats may reflect a compensatory
      response to dampen the elevated levels of intrarenal ANG II.

PMID- 16403836
TI  - Similar chloride channels in the connecting tubule and cortical collecting duct
      of the mouse kidney.
AB  - Using the patch-clamp technique, we investigated Cl- channels on the basolateral
      membrane of the connecting tubule (CNT) and cortical collecting duct (CCD). We
      found a approximately 10-pS channel in CNT cell-attached patches. Substitution of
      sodium gluconate for NaCl in the pipette shifted the reversal potential by +25
      mV, whereas N-methyl-D-gluconate chloride had no effect, indicating anion
      selectivity. On inside-out patches, we determined a selectivity sequence of Cl- >
      Br- approximately NO3(-) > F-, which is compatible with that of ClC-K2, a Cl-
      channel in the distal nephron. In addition, the number of open channels (NP(o))
      measured in cell-attached patches was significantly increased when Ca2+
      concentration or pH in the pipette was increased, which is another characteristic
      of ClC-K. These findings suggest that the basis for this channel is ClC-K2. A
      similar Cl- channel was found in CCD patches. Because CNT and CCD are
      heterogeneous tissues, we studied the cellular distribution of the Cl- channel
      using recording conditions (KCl-rich solution in the pipette) that allowed us to
      detect simultaneously Cl- channels and inwardly rectifying K+ channels. We
      detected Cl- channels alone in 45% and 42% and K+ channels alone in 51% and 58%
      of CNT and CCD patches, respectively. Cl- and K+ channels were recorded
      simultaneously from two patches (4% of patches) in the CNT and from none of the
      patches in the CCD. This indicates that Cl- and K+ channels are located in
      different cell types, which we suggest may be the intercalated cells and
      principal cells, respectively.

PMID- 16403835
TI  - Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia
      reperfusion injury in mouse kidney.
AB  - The mechanisms involved in renal ischemia-reperfusion injury (IRI) are complex
      and appear to involve the early participation of bone marrow-derived cells. T
      lymphocytes participate in the pathogenesis of IRI. Sphingosine 1-phosphate (S1P)
      induces peripheral T cell depletion. Therefore, we hypothesized that S1P1
      receptor activation protects kidney from IRI. FTY-720, a non-receptor-selective
      sphingosine analog, was given intraperitoneally to C57BL/6 mice, and animals were
      subjected to ischemia for 32 min followed by reperfusion for 24 h. Plasma
      creatinine, blood count, myeloperoxidase (MPO) activity, and renal histology were
      determined. IRI led to a marked increase in plasma creatinine, MPO activity,
      leukocyte infiltration, and vascular permeability. FTY-720 significantly
      decreased plasma creatinine in a dose-response manner with a maximal reduction of
      approximately 73 and approximately 69% with doses of 240 and 48 microg/kg,
      respectively. MPO, leukocyte infiltration, vascular permeability, and peripheral
      blood lymphocyte counts were markedly decreased with FTY-720 treatment. The
      protective effect of FTY-720 was reversed with VPC-44116, a selective S1P1
      receptor antagonist. Furthermore, SEW-2871, a selective S1P1 agonist,
      significantly decreased plasma creatinine in a dose-response manner with a
      maximal reduction of approximately 70% with a dose of 10 mg/kg. Analysis of
      kidneys by light microscopy revealed minimal histological signs of ischemic
      injury with FTY-720 or SEW-2871 treatment compared with the vehicle group. Using
      RT-PCR, we found a time-dependent increase in the S1P1 mRNA expression following
      IRI that begins after 2 h with the maximum expression at approximately 4 h. We
      conclude that the protective effect of FTY-720 is due primarily to activation of
      S1P1 receptors. The mechanism of protection is not known but may be related to
      peripheral lymphocyte depletion or direct effects on kidney cells expressing S1P1
      receptor.

PMID- 16403837
TI  - FXYD proteins: new regulators of Na-K-ATPase.
AB  - FXYD proteins belong to a family of small-membrane proteins. Recent experimental
      evidence suggests that at least five of the seven members of this family, FXYD1
      (phospholemman), FXYD2 (gamma-subunit of Na-K-ATPase), FXYD3 (Mat-8), FXYD4
      (CHIF), and FXYD7, are auxiliary subunits of Na-K-ATPase and regulate Na-K-ATPase
      activity in a tissue- and isoform-specific way. These results highlight the
      complexity of the regulation of Na+ and K+ handling by Na-K-ATPase, which is
      necessary to ensure appropriate tissue functions such as renal Na+ reabsorption,
      muscle contractility, and neuronal excitability. Moreover, a mutation in FXYD2
      has been linked to cases of human hypomagnesemia, indicating that perturbations
      in the regulation of Na-K-ATPase by FXYD proteins may be critically involved in
      pathophysiological states. A better understanding of this novel regulatory
      mechanism of Na-K-ATPase should help in learning more about its role in
      pathophysiological states. This review summarizes the present knowledge of the
      role of FXYD proteins in the modulation of Na-K-ATPase as well as of other
      proteins, their regulation, and their structure-function relationship.

PMID- 16403839
TI  - Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential
      consequences.
AB  - Chronic renal failure (CRF) results in profound lipid disorders, which stem
      largely from dysregulation of high-density lipoprotein (HDL) and triglyceride
      rich lipoprotein metabolism. Specifically, maturation of HDL is impaired and its
      composition is altered in CRF. In addition, clearance of triglyceride-rich
      lipoproteins and their atherogenic remnants is impaired, their composition is
      altered, and their plasma concentrations are elevated in CRF. Impaired maturation
      of HDL in CRF is primarily due to downregulation of lecithin-cholesterol
      acyltransferase (LCAT) and, to a lesser extent, increased plasma cholesteryl
      ester transfer protein (CETP). Triglyceride enrichment of HDL in CRF is primarily
      due to hepatic lipase deficiency and elevated CETP activity. The CRF-induced
      hypertriglyceridemia, abnormal composition, and impaired clearance of
      triglyceride-rich lipoproteins and their remnants are primarily due to
      downregulation of lipoprotein lipase, hepatic lipase, and the very-low-density
      lipoprotein receptor, as well as, upregulation of hepatic acyl-CoA cholesterol
      acyltransferase (ACAT). In addition, impaired HDL metabolism contributes to the
      disturbances of triglyceride-rich lipoprotein metabolism. These abnormalities are
      compounded by downregulation of apolipoproteins apoA-I, apoA-II, and apoC-II in
      CRF. Together, these abnormalities may contribute to the risk of arteriosclerotic
      cardiovascular disease and may adversely affect progression of renal disease and
      energy metabolism in CRF.

PMID- 16403838
TI  - Molecular physiology of renal organic anion transporters.
AB  - Recent advances in molecular biology have identified three organic anion
      transporter families: the organic anion transporter (OAT) family encoded by
      SLC22A, the organic anion transporting peptide (OATP) family encoded by SLC21A
      (SLCO), and the multidrug resistance-associated protein (MRP) family encoded by
      ABCC. These families play critical roles in the transepithelial transport of
      organic anions in the kidneys as well as in other tissues such as the liver and
      brain. Among these families, the OAT family plays the central role in renal
      organic anion transport. Knowledge of these three families at the molecular
      level, such as substrate selectivity, tissue distribution, and gene localization,
      is rapidly increasing. In this review, we will give an overview of molecular
      information on renal organic anion transporters and describe recent topics such
      as the regulatory mechanisms and molecular physiology of urate transport. We will
      also discuss the physiological roles of each organic anion transporter in the
      light of the transepithelial transport of organic anions in the kidneys.

PMID- 16403840
TI  - Transcriptomes of purified gastric ECL and parietal cells: identification of a
      novel pathway regulating acid secretion.
AB  - The gastric entero-chromaffin-like (ECL) cell plays a key regulatory role in
      peripheral regulation of acid secretion due to the release of histamine that
      stimulates acid secretion by the parietal cell. Studies in intact animals,
      gastric glands, and isolated cells after short-term culture have shown expression
      of stimulatory CCK2 and PAC1 and inhibitory SST2 and Gal1 receptors as well as
      histidine decarboxylase. However, the pattern of its gene expression as a
      neuroendocrine cell has not been explored. Comparison of gene expression by 95%
      pure ECL cells obtained by density gradient, elutriation, and fluorescence
      assisted cell sorting with isolates of the intact fundic gastric epithelium
      (i.e., "subtractive hybridization") identified a variety of additional expressed
      gene families characteristic of this neuroendocrine cell. These include genes 1)
      involved in neuropeptide synthesis and secretory vesicle exocytosis, 2) involved
      in control of inflammation, 3) implicated in healing of the epithelium, 4)
      encoding inhibitory Gi protein-coupled receptors, 5) playing a role in
      neuroendocrine regulation of food intake, and 6) encoding proteins likely
      involved in maintenance of circadian rhythm, in addition to the ECL cell-specific
      genes histidine decarboxylase and monoamine transporter. Particularly, the
      inhibitory apelin receptor gene, APJ, was highly expressed in the ECL cell
      preparation. Because parietal cells express apelin, immunohistochemical and
      functional studies showed that there is an inhibitory feed back loop between the
      parietal and ECL cell during gastrin stimulation, providing evidence for a novel
      pathway of downregulation of acid secretion due to interaction between these two
      cell types.

PMID- 16403841
TI  - Identification and function of hypoxia-response genes in Drosophila melanogaster.
AB  - Hypoxia, an insufficient level of oxygen in the cell, occurs during normal
      activity and also in pathological conditions such as ischemia and tumorigenesis.
      Although many hypoxia-response genes have been identified, an understanding of
      the functional role for these genes in the living animal is lacking. Here we
      present a genome-wide study of gene expression changes during hypoxia and then
      functionally test a subset of these genes for roles in survival and recovery from
      hypoxia. We found 79 genes with increased mRNA levels when adult flies were
      treated with 0.5% O2 for 6 h. A subset of these genes had detectably increased
      levels in as short as 1 h of low-oxygen treatment. Mild hypoxia levels resulted
      in an increase in transcription levels for only 20 genes. Viability during
      hypoxia and recovery time from hypoxia-induced paralysis was examined in flies
      with a reduction in activity in hypoxia-response genes. The observed decreased
      viability and increased recovery time from paralysis in many of the lines
      demonstrate that the increased transcript levels seen after hypoxia are important
      for the response to low oxygen.

PMID- 16403842
TI  - Chloroplast-mediated regulation of nuclear genes in Arabidopsis thaliana in the
      absence of light stress.
AB  - Chloroplast signaling involves mechanisms to relay information from chloroplasts
      to the nucleus, to change nuclear gene expression in response to environmental
      cues. Aside from reactive oxygen species (ROS) produced under stress conditions,
      changes in the reduction/oxidation state of photosynthetic electron transfer
      components or coupled compounds in the stroma and the accumulation of
      photosynthesis-derived metabolites are likely origins of chloroplast signals. We
      attempted to investigate the origin of the signals from chloroplasts in mature
      Arabidopsis leaves by differentially modulating the redox states of the
      plastoquinone pool and components on the reducing side of photosystem I, as well
      as the rate of CO2 fixation, while avoiding the production of ROS by excess
      light. Differential expression of several nuclear photosynthesis genes, including
      a set of Calvin cycle enzymes, was recorded. These responded to the stromal redox
      conditions under prevailing light conditions but were independent of the redox
      state of the plastoquinone pool. The steady-state CO2 fixation rate was reflected
      in the orchestration of the expression of a number of genes encoding cytoplasmic
      proteins, including several glycolysis genes and the trehalose-6-phosphate
      synthase gene, and also the chloroplast-targeted chaperone DnaJ. Clearly, in
      mature leaves, the redox state of the compounds on the reducing side of
      photosystem I is of greater importance in light-dependent modulation of nuclear
      gene expression than the redox state of the plastoquinone pool, particularly at
      early signaling phases. It also became apparent that photosynthesis-mediated
      generation of metabolites or signaling molecules is involved in the relay of
      information from chloroplast to nucleus.

PMID- 16403843
TI  - Three-color cDNA microarrays with prehybridization quality control yield gene
      expression data comparable to that of commercial platforms.
AB  - Despite their lower cost and high content flexibility, a limitation of in-house
      prepared arrays has been their susceptibility to quality control (QC) issues and
      lack of QC standards across laboratories. Therefore, we developed a novel three
      color array system that allows prehybridization QC as well as the Matarray
      software to facilitate acquisition of accurate gene expression data. In this
      study, we compared performance of our rat cDNA array to the Affymetrix RG-U34A
      and Agilent G4130A arrays using 2,824 UniGenes represented on all three arrays.
      Before data filtering, poor interplatform agreement was observed; however, after
      data filtering, differentially expressed UniGenes exhibited correlation
      coefficients of 0.91, 0.88, and 0.92 between the Affymetrix vs. Agilent,
      Affymetrix vs. cDNA, and Agilent vs. cDNA arrays, respectively. The Affymetrix,
      Agilent, and cDNA arrays agreed well with quantitative RT-PCR conducted on 42
      UniGenes, yielding correlation coefficients of 0.90, 0.90, and 0.96,
      respectively. Each platform underestimated ratios relative to quantitative RT
      PCR, possessing respective slopes of 0.86 (R2 = 0.81), 0.65 (R2 = 0.81), and 0.70
      (R2 = 0.92). Overall, these data show that the combination of our novel technical
      and analytic approaches yield an accurate platform for functional genomics that
      is concordant with commercial discovery arrays in terms of identifying regulated
      genes and pathways.

PMID- 16403844
TI  - Gene expression profiles of peripheral blood leukocytes after endotoxin challenge
      in humans.
AB  - To define gene expression profiles that occur during the initial activation of
      human innate immunity, we administered intravenous endotoxin (n = 8) or saline (n
      = 4) to healthy subjects and hybridized RNA from blood mononuclear cells (0, 0.5,
      6, 24, 168 h) or whole blood (0, 3, 6, 24, 168 h) to oligonucleotide probe
      arrays. The greatest change in mononuclear cell gene expression occurred at 6 h
      (439 induced and 428 repressed genes, 1% false discovery rate, and 50% fold
      change) including increased expression of genes associated with pathogen
      recognition molecules and signaling cascades linked to receptors associated with
      cell mobility and activation. Induced defense response genes included cytokines,
      chemokines, and their respective receptors, acute-phase transcription factors,
      proteases, arachidonate metabolites, and oxidases. Repressed defense response
      genes included those associated with co-stimulatory molecules, T and cytotoxic
      lymphocytes, natural killer (NK) cells, and protein synthesis. Gene expression
      profiles of whole blood had similar biological themes. Over 100 genes not
      typically associated with acute inflammation were differentially regulated after
      endotoxin. By 24 h, gene expression had returned to baseline values. Thus the
      inflammatory response of circulating leukocytes to endotoxin in humans is
      characterized by a rapid amplification and subsidence of gene expression. These
      results indicate that a single intravascular exposure to endotoxin produces a
      large but temporally short perturbation of the blood transcriptome.

PMID- 16403845
TI  - Elimination of allosteric modulation of myocardial KATP channels by ATP and
      protons in two Kir6.2 polymorphisms found in sudden cardiac death.
AB  - The major cause of sudden cardiac death (SCD) is ventricular arrhythmias due to
      unstable myocardial electrical activity in which the ATP-sensitive K+ (KATP)
      channels play a role. Genetic disruption of these channels predisposes the
      myocardium to arrhythmias. Two point mutations in the Kir6.2 subunit are found in
      SCD with acute myocardial infarction. Here we show evidence for the functional
      consequences of the P266T and R371H variants. Baseline single-channel properties,
      expression density, and channel modulations were studied in patch clamp. We
      focused on channel modulations by intracellular ATP and protons, as the
      concentration of these two important KATP channel regulators changes widely with
      hypoxic ischemia. We found that both variants expressed functional currents even
      though they occur at two highly conserved regions. The open state probability of
      P266T was twice as high as the wild-type (WT) channel, whereas its channel
      density was only approximately 20% of the WT channel. Although the outward
      current was not affected by these two mutations at neutral pH, it was
      approximately 20% lower at acidic pH in the P266T than in the WT channel. Both
      P266T and R371H mutations significantly reduced ATP sensitivity and increased pH
      sensitivity. More dramatically, allosteric regulation by intracellular ATP and
      protons was almost completely eliminated in the polymorphic P266T and R371H
      channels. Such an abnormality was seen in both inward and outward currents. Given
      the importance and beneficial effects of allosteric regulation in cellular
      responses to metabolic stress, the loss of such a regulatory mechanism in the
      P266T and R371H variants appears consistent with the adverse consequences
      occurring during acute myocardial infarction in patients.

PMID- 16403846
TI  - mRNA expression in mouse hypothalamus and basal forebrain during influenza
      infection: a novel model for sleep regulation.
AB  - After influenza infection, C57BL/6J mice develop increased slow-wave sleep (SWS)
      during the dark phase of the day-night cycle, whereas BALB/cByJ mice develop
      decreased SWS during the light phase. A previous analysis of CXB recombinant
      inbred mice revealed a quantitative trait locus (QTL) designated Srilp (sleep
      response to influenza, light phase) that was related to expression of the
      BALB/cByJ sleep phenotype. Srilp was localized to the 10- to 12-cM region of
      mouse Chr 6 between D6Mit74 and D6Mit188. Temt (thioether S-methyltransferase),
      which is located at region B3 of Chr 6, is a potential candidate gene for Srilp.
      We evaluated the expression of Temt and other Srilp candidate genes in
      hypothalamus and basal forebrain of uninfected and influenza-infected C57BL/6J
      and BALB/cByJ mice. We report here that Temt expression varies significantly with
      respect to mouse strain, health status, brain region, and day-night phase.
      C57BL/6J mice show day-night variation in Temt expression in hypothalamus, but
      BALB/cByJ mice do not. Temt expression in basal forebrain is much higher in
      C57BL/6J mice than in BALB/cByJ mice. During influenza infection, both C57BL/6J
      and BALB/cByJ mice show reduced Temt mRNA in basal forebrain at 30 h
      postinoculation, but expression remains much lower in the BALB/cByJ strain. In
      contrast, prostaglandin-D-synthase (Ptgds) and lipocalin 2 (Lcn2) mRNA increase
      in basal forebrain of both strains after influenza infection. Administration of
      the TEMT inhibitor sinefungin reduces sleep in uninfected BALB/cByJ mice and
      attenuates influenza-induced sleep enhancement in C57BL/6J mice. These data
      suggest that strain- and infection-related alterations in sleep may be influenced
      by Temt expression and perhaps by subsequent effects on prostaglandin metabolism.

PMID- 16403847
TI  - Solar disinfection of water for diarrhoeal prevention in southern India.
AB  - AIMS: To evaluate the efficacy and acceptability of solar irradiation in the
      prevention of diarrhoeal morbidity in children under 5 years of age, in an urban
      slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to
      receive drinking water that had been subjected to solar disinfection in
      polyethylene terephthalate bottles. One hundred age and sex matched controls were
      also selected. Both groups were followed by weekly home visits for a period of
      six months for any diarrhoeal morbidity. At the end of the follow up period, the
      acceptability of the intervention was assessed by interviews, questionnaires, and
      focus group discussions. RESULTS: There was significant reduction in the
      incidence, duration, and severity of diarrhoea in children receiving solar
      disinfected water, despite 86% of the children drinking water other than that
      treated by the intervention. The incidence of diarrhoea in the intervention group
      was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence
      rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by
      40% by using solar disinfection. In qualitative evaluation of acceptability, most
      women felt that solar disinfection was a feasible and sustainable method of
      disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive,
      effective, and acceptable method of increasing water safety in a resource limited
      environment, and can significantly decrease diarrhoeal morbidity in children.

PMID- 16403848
TI  - Mycophenolate mofetil treatment of myasthenia gravis.
AB  - OBJECTIVE: To review published literature evaluating the effectiveness of
      mycophenolate mofetil for the treatment of myasthenia gravis (MG). DATA SOURCES:
      Searches of MEDLINE (1966-August 2005) and Cochrane Database (1993-August 2005)
      were conducted. Studies conducted in humans and published in English were
      retrieved. Additional data were identified through subsequent bibliographic
      reviews. DATA SYNTHESIS: Interruption of T- and B-lymphocyte proliferation in
      various autoimmune diseases has been investigated. Mycophenolate is known to
      inhibit lymphocyte proliferation and has shown improved clinical responses in
      several autoimmune diseases including lupus erythematosus, rheumatoid arthritis,
      and systemic vasculitis. Data suggesting similar benefits in MG treatment have
      been reported in case reports, retrospective analyses, an open-label trial, and a
      randomized, double-blind trial. CONCLUSIONS: Limited evidence from retrospective
      analyses and clinical trials suggests that mycophenolate is a possible treatment
      option for patients with MG. Improvement in clinical symptoms and a steroid
      sparing effect have been reported when mycophenolate is used in this patient
      population. Larger, randomized, controlled, and comparative trials are needed to
      establish optimal dose, time to effect, specific therapeutic role, and long-term
      safety for mycophenolate when used for treating MG.

PMID- 16403849
TI  - Current status of cetuximab for the treatment of patients with solid tumors.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical evidence, and
      safety, as well as the potential directions for use, of the epidermal growth
      factor receptor (EGFR) monoclonal antibody cetuximab. DATA SOURCES: A MEDLINE
      search (1966-December 2005) was conducted using the following terms: cetuximab,
      Erbitux, C225, epidermal growth factor receptor, and EGFR. Additional information
      was obtained via meeting abstracts, bibliographies from relevant articles,
      national guidelines, and the manufacturer. STUDY SELECTION AND DATA EXTRACTION:
      Preclinical and clinical trials utilizing cetuximab in the treatment of solid
      tumors were selected from the data sources. All published, randomized clinical
      trials involving cetuximab in treatment of metastatic colorectal cancer and
      studies providing a description of the pharmacology, pharmacokinetics, safety, or
      efficacy were included in this review. DATA SYNTHESIS: Many solid tumors
      overexpress EGFR, making it an ideal target for anticancer agents. Cetuximab is
      the only EGFR monoclonal antibody commercially available and is approved for the
      treatment of EGFR-expressing, metastatic colorectal cancer in patients refractory
      or intolerant to irinotecan. Data on patients with other solid tumors are
      encouraging with cetuximab used as monotherapy or in combination with
      chemotherapy, radiation, or other targeted agents. Common adverse effects include
      dermatologic and hypersensitivity reactions. CONCLUSIONS: Further clinical data
      are necessary to clearly define the role of cetuximab in the treatment of
      patients with solid malignancies, with emphasis on survival and quality-of-life
      benefits relative to its cost.

PMID- 16403850
TI  - Role of lenalidomide in the treatment of multiple myeloma and myelodysplastic
      syndrome.
AB  - OBJECTIVE: To evaluate lenalidomide in the treatment of multiple myeloma and
      myelodysplastic syndrome (MDS). DATA SOURCES: Clinical literature was accessed
      through MEDLINE (1966-August 2005), Science Citation Index (1980-August 2005),
      and Proceedings of the American Society of Hematology (2000-2004). DATA
      SYNTHESIS: New analogs of thalidomide have been synthesized that are more potent
      and less toxic. Lenalidomide (CC-5013) is currently in Phase III trials for the
      treatment of multiple myeloma and MDS. Phase II trials demonstrated
      lenalidomide's efficacy in patients refractory to thalidomide. The full potential
      of this agent has yet to be proven, but preliminary data seem promising.
      CONCLUSIONS: Lenalidomide is a potent immunomodulating drug that offers different
      mechanisms of action and therapeutic potential for the treatment of multiple
      myeloma, MDS, and other malignancies.

PMID- 16403851
TI  - Emerging treatments for bipolar disorder: safety and adverse effect profiles.
AB  - OBJECTIVE: To provide an overview of the safety and tolerability of newer agents
      used to treat bipolar disorder (BPD) and provide clinicians with management
      strategies for drug-related toxicity and adverse effects. DATA SOURCES: MEDLINE
      was searched through July 2005 for BPD treatment, adverse effects, tolerability,
      safety, emerging agents, atypical antipsychotics, new antiepileptic drugs (AEDs),
      risperidone, quetiapine, clozapine, ziprasidone, aripiprazole, lamotrigine,
      topiramate, gabapentin, oxcarbazepine, and olanzapine. STUDY SELECTION AND DATA
      EXTRACTION: Results from randomized controlled trials, open-label studies, and
      reviews are described. DATA SYNTHESIS: Emerging agents recently approved for BPD
      include atypical antipsychotics and new AEDs. Safety and tolerability are as
      important as efficacy because poor adherence in BPD worsens outcome; metabolic
      and other comorbidities pose specific challenges; and manic patients often
      require combination therapy, which increases adverse effects. Most atypical
      antipsychotics cause fewer extrapyramidal symptoms than conventional
      antipsychotics, but may cause more weight gain and metabolic complications. The
      newer AEDs generally cause less weight gain than the older agents, and some even
      promote weight loss. Several newer AEDs used in BPD also offer the advantages of
      fewer drug interactions and less need for therapeutic drug monitoring compared
      with older AEDs. CONCLUSIONS: Pending the results of ongoing controlled studies,
      several emerging agents may be useful additions to the therapeutic arsenal for
      BPD.

PMID- 16403852
TI  - Concentration-dependent kinetics of acetylcholinesterase inhibition by the
      organophosphate paraoxon.
AB  - For decades the interaction of the anticholinesterase organophosphorus compounds
      with acetylcholinesterase has been characterized as a straightforward
      phosphylation of the active site serine (Ser-203) which can be described
      kinetically by the inhibitory rate constant k(i). However, more recently certain
      kinetic complexities in the inhibition of acetylcholinesterase by
      organophosphates such as paraoxon (O,O-diethyl O-(p-nitrophenyl) phosphate) and
      chlorpyrifos oxon (O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphate) have
      raised questions regarding the adequacy of the kinetic scheme on which k(i) is
      based. The present article documents conditions in which the inhibitory capacity
      of paraoxon towards human recombinant acetylcholinesterase appears to change as a
      function of oxon concentration (as evidenced by a changing k(i)), with the
      inhibitory capacity of individual oxon molecules increasing at lower oxon
      concentrations. Optimization of a computer model based on an Ordered Uni Bi
      kinetic mechanism for phosphylation of acetylcholinesterse determined k(1) to be
      0.5 nM(-1)h(-1), and k(-1) to be 169.5 h(-1). These values were used in a
      comparison of the Ordered Uni Bi model versus a k(i) model in order to assess the
      capacity of k(i) to describe accurately the inhibition of acetylcholinesterase by
      paraoxon. Interestingly, the k(i) model was accurate only at equilibrium (or near
      equilibrium), and when the inhibitor concentration was well below its K(d)
      (pseudo first order conditions). Comparisons of the Ordered Uni Bi and k(i)
      models demonstrate the changing k(i) as a function of inhibitor concentrations is
      not an artifact resulting from inappropriate inhibitor concentrations.

PMID- 16403853
TI  - Comparison of in vitro and in vivo estrogenic activity of UV filters in fish.
AB  - In this work, we evaluate whether in vitro systems are good predictors for in
      vivo estrogenic activity in fish. We focus on UV filters being used in sunscreens
      and in UV stabilization of materials. First, we determined the estrogenic
      activity of 23 UV filters and one UV filter metabolite employing a recombinant
      yeast carrying the estrogen receptor of rainbow trout (rtERalpha) and made
      comparisons with yeast carrying the human hERalpha for receptor specificity.
      Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4
      hydroxybenzophenone, 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed
      full dose-response curves with maximal responses of 81-115%, whereas 3
      benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and
      benzophenone-4 displayed lower maximal responses of 15-74%. Whereas the activity
      of 17beta-estradiol was lower in the rtERalpha than the hERalpha assay, the
      activities of UV filters were similar or relatively higher in rtERalpha,
      indicating different relative binding activities of both ER. Subsequently, we
      analyzed whether the in vitro estrogenicity of eight UV filters is also displayed
      in vivo in fathead minnows by the induction potential of vitellogenin after 14
      days of aqueous exposure. Of the three active compounds in vivo, 3BC induced
      vitellogenin at lower concentrations (435 microg/l) than BP1 (4919 microg/l) and
      BP2 (8783 microg/l). The study shows, for the first time, estrogenic activities
      of UV filters in fish both in vitro and in vivo. Thus we propose that receptor
      based assays should be used for in vitro screening prior to in vivo testing,
      leading to environmental risk assessments based on combined, complementary, and
      appropriate species-related assays for hormonal activity.

PMID- 16403854
TI  - dbZach: A MIAME-compliant toxicogenomic supportive relational database.
AB  - Quantitative risk assessment and the elucidation of mechanisms of toxicity
      requires computational infrastructure and innovative analysis approaches that
      systematically consider available data at all levels of biological organization.
      dbZach (http://dbzach.fst.msu.edu) is a modular relational database with
      associated data insertion, retrieval, and mining tools that manages traditional
      toxicology and complementary toxicogenomic data to facilitate comprehensive data
      integration, analysis, and sharing. It consists of four Core Subsystems (i.e.,
      Clones, Genes, Sample Annotation, and Protocols), four Experimental Subsystems
      (i.e., Microarray, Affymetrix, Real-Time PCR, and Toxicology), and three
      Computational Subsystems (i.e., Gene Regulation, Pathways, Orthology) that comply
      with the Minimum Information About a Microarray Experiment (MIAME) standard. It
      is capable of including emerging technologies and other model systems, including
      ecologically relevant species. dbZach represents an enterprise toxicogenomic data
      management system which facilitates data integration and analysis, and reduces
      uncertainties in the continuum from initial exposure to toxicity while
      facilitating more comprehensive elucidations of mechanisms of toxicity and
      supporting mechanistically-based quantitative risk assessment.

PMID- 16403855
TI  - List of new names and new combinations previously effectively, but not validly,
      published.
AB  - The purpose of this announcement is to effect the valid publication of the
      following new names and new combinations under the procedure described in the
      Bacteriological Code (1990 Revision). Authors and other individuals wishing to
      have new names and/or combinations included in future lists should send three
      copies of the pertinent reprint or photocopies thereof to the IJSEM Editorial
      Office for confirmation that all of the other requirements for valid publication
      have been met. It is also a requirement of IJSEM and the ICSP that authors of new
      species, new subspecies and new combinations provide evidence that types are
      deposited in two recognized culture collections in two different countries (i.e.
      documents certifying deposition and availability of type strains). It should be
      noted that the date of valid publication of these new names and combinations is
      the date of publication of this list, not the date of the original publication of
      the names and combinations. The authors of the new names and combinations are as
      given below, and these authors' names will be included in the author index of the
      present issue and in the volume author index. Inclusion of a name on these lists
      validates the publication of the name and thereby makes it available in
      bacteriological nomenclature. The inclusion of a name on this list is not to be
      construed as taxonomic acceptance of the taxon to which the name is applied.
      Indeed, some of these names may, in time, be shown to be synonyms, or the
      organisms may be transferred to another genus, thus necessitating the creation of
      a new combination.

PMID- 16403856
TI  - Notification that new names and new combinations have appeared in volume 55, part
      5, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles). Taxonomic opinions included in
      this List (i.e. the creation of synonyms or the emendation of circumscriptions)
      cannot be considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission.

PMID- 16403857
TI  - Notification of changes in taxonomic opinion previously published outside the
      IJSEM.
AB  - The Bacteriological Code deals with the nomenclature of prokaryotes. This may
      include existing names (the Approved Lists of Bacterial Names) as well as new
      names and new combinations. In this sense the Code is also dealing indirectly
      with taxonomic opinions. However, as with most codes of nomenclature there are no
      mechanisms for formally recording taxonomic opinions that do not involve the
      creation of new names or new combinations. In particular, it would be desirable
      for taxonomic opinions resulting from the creation of synonyms or emended
      descriptions to be made widely available to the public. In 2004, the Editorial
      Board of the International Journal of Systematic and Evolutionary Microbiology
      (IJSEM) agreed unanimously that it was desirable to cover such changes in
      taxonomic opinions (i.e. the creation of synonyms or the emendation of
      circumscriptions) previously published outside the IJSEM, and to introduce a List
      of Changes in Taxonomic Opinion [Notification of changes in taxonomic opinion
      previously published outside the IJSEM; Euzeby et al. (2004). Int J Syst Evol
      Microbiol 54, 1429-1430]. Scientists wishing to have changes in taxonomic opinion
      included in future lists should send one copy of the pertinent reprint or a
      photocopy or a PDF file thereof to the IJSEM Editorial Office or to the Lists
      Editor. It must be stressed that the date of proposed taxonomic changes is the
      date of the original publication not the date of publication of the list.
      Taxonomic opinions included in the List of Changes in Taxonomic Opinion cannot be
      considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission. The names that are to be used are those that are the 'correct names'
      (in the sense of Principle 6) in the opinion of the bacteriologist, with a given
      circumscription, position and rank. A particular name, circumscription, position
      and rank does not have to be adopted in all circumstances. Consequently, the List
      of Changes in Taxonomic Opinion must be considered as a service to bacteriology
      and it has no 'official character', other than providing a centralized point for
      registering/indexing such changes in a way that makes them easily accessible to
      the scientific community.

PMID- 16403858
TI  - Mycoplasma and Eperythrozoon (Mycoplasmataceae). Comments on a recent paper.

PMID- 16403859
TI  - Pilibacter termitis gen. nov., sp. nov., a lactic acid bacterium from the hindgut
      of the Formosan subterranean termite (Coptotermes formosanus).
AB  - A previously undescribed anaerobic, heterofermentative, non-spore-forming, Gram
      positive rod was isolated from the hindgut of the Formosan subterranean termite
      Coptotermes formosanus Shiraki. The DNA G+C content of this bacterium was 37.8
      mol%. Sequence analysis of the 16S rRNA gene revealed that this organism is
      related to, but distinct from, several genera of lactic acid bacteria,
      principally several species of the genus Enterococcus. Phenotypic traits that
      serve to separate this organism from related genera include high levels of the
      cellular fatty acid C18 : 1omega9c and the production of ethanol along with
      lactic acid as fermentation products. Based on the collected phylogenetic and
      phenotypic evidence, it is proposed that the unknown organism represents a novel
      species in a new genus, Pilibacter termitis gen. nov., sp. nov. The type strain
      is TI-1T (= ATCC BAA-1030T = CCUG 49613T).

PMID- 16403860
TI  - Acetobacter oeni sp. nov., isolated from spoiled red wine.
AB  - A bacterial strain, designated B13T, was isolated from spoiled red wine from the
      Dao region, Portugal. The strain was Gram-negative, strictly aerobic, rod-shaped
      and motile. Phylogenetic analysis on the basis of 16S rRNA gene sequences
      indicated that B13T belonged to the genus Acetobacter within the
      Alphaproteobacteria. The closest related species was Acetobacter aceti, with 98.4
      % 16S rRNA gene sequence similarity. DNA-DNA hybridization showed that B13T
      constituted a taxon separate from the Acetobacter species with validly published
      names. The DNA G+C content of B13T was 58.1 mol%. Phenotypic characteristics of
      B13T allowed its differentiation from the recognized Acetobacter species. B13T
      produced 5-ketogluconic acid from glucose, but no 2-ketogluconic acid. It
      produced catalase, but no oxidase. It utilized glycerol, but not maltose, ethanol
      or methanol as carbon sources. On the basis of the results obtained, B13T
      represents a novel species for which the name Acetobacter oeni sp. nov. is
      proposed. The type strain is B13T (= LMG 21952T = CECT 5830T).

PMID- 16403861
TI  - Roseomonas lacus sp. nov., isolated from freshwater lake sediment.
AB  - An aerobic, Gram-negative bacterial strain, TH-G33T, was isolated from freshwater
      sediment of Taihu Lake in China. The taxonomy of strain TH-G33T was studied by
      using phenotypic and phylogenetic methods. Cells of strain TH-G33T were coccoid
      rods or rods and formed colourless to pale-pink colonies on nutrient agar.
      Phylogenetic analysis based on nearly complete 16S rRNA gene sequences showed
      that strain TH-G33T was related to Roseomonas mucosa (94.4 %), Roseomonas
      gilardii subsp. gilardii (94.1 %), Roseomonas gilardii subsp. rosea (94.8 %) and
      Roseomonas cervicalis (93.9 %). Cells contained ubiquinone 10 (Q-10) as the major
      quinone and the G+C content was 71.9 mol%. Thus, strain TH-G33T represents a
      novel species of the genus Roseomonas, for which the name Roseomonas lacus sp.
      nov. is proposed. The type strain is TH-G33T (= CGMCC 1.3617T = JCM 13283T).

PMID- 16403862
TI  - Lactobacillus sobrius sp. nov., abundant in the intestine of weaning piglets.
AB  - To obtain porcine isolates related to Lactobacillus amylovorus, we screened
      strains from piglet intestine grown on Lactobacillus-specific MRS agar for
      hybridization to a fluorescent 16S rRNA-targeted DNA probe. Six strains were
      isolated and further characterized by phenotypic and molecular taxonomic methods.
      The isolates were Gram-positive, catalase-negative, facultatively anaerobic rods.
      They had similar phenotypic characteristics and displayed genomic DNA-DNA
      relatedness values of >78 % to each other, indicating that they belong to a
      single species. Comparative 16S rRNA gene sequence analysis demonstrated that the
      novel isolates were members of Lactobacillus rRNA group I, which includes
      Lactobacillus delbrueckii, the type species of the genus. Based on 16S rRNA gene
      sequence similarity, Lactobacillus kitasatonis (99 %), Lactobacillus crispatus
      (98 %) and Lactobacillus amylovorus (97 %) were the nearest relatives of the
      novel isolates, but their DNA-DNA relatedness was found to be lower than 49 %.
      One of the isolates, strain OTU171-001T, was further characterized using
      physiological and biochemical tests. Together, the results enabled genotypic and
      phenotypic differentiation of strain OTU171-001T from the other species that
      showed 16S rRNA gene sequence similarity values greater than 97 %. Strain OTU171
      001T merits species status and the name Lactobacillus sobrius sp. nov. is
      proposed. The type strain is OTU171-001T (= DSM 16698T = NCCB 100067T).

PMID- 16403863
TI  - Colwellia aestuarii sp. nov., isolated from a tidal flat sediment in Korea.
AB  - A novel Colwellia-like bacterial strain, SMK-10T, was isolated from a tidal flat
      sediment in Korea and subjected to a polyphasic taxonomic analysis. Cells of
      strain SMK-10T were Gram-negative, motile, greyish yellow-pigmented, curved rods.
      Optimal growth occurred at 25-30 degrees C and in the presence of 2-3 % (w/v)
      NaCl. Strain SMK-10T contained Q-8 as the predominant ubiquinone and C(16 :
      1)omega7c and/or iso-C(15 : 0) 2-OH, C(17 : 1), C(15 : 1) and iso-C(16 : 0) as
      major fatty acids. The DNA G+C content was 39.3 mol%. Phylogenetic trees based on
      16S rRNA gene sequence analysis showed that strain SMK-10T belonged to the genus
      Colwellia. 16S rRNA gene sequence similarity values (94.7-96.7 %) to the type
      strains of all other Colwellia species and various differential phenotypic
      properties were sufficient to distinguish strain SMK-10T from recognized
      Colwellia species. On the basis of its phenotypic properties and phylogenetic
      distinctiveness, strain SMK-10T (= KCTC 12480T = DSM 17314T) is classified as the
      type strain of a novel Colwellia species, for which the name Colwellia aestuarii
      sp. nov. is proposed.

PMID- 16403864
TI  - Paludibacter propionicigenes gen. nov., sp. nov., a novel strictly anaerobic,
      Gram-negative, propionate-producing bacterium isolated from plant residue in
      irrigated rice-field soil in Japan.
AB  - A strictly anaerobic, propionate-producing bacterial strain (WB4T) isolated from
      rice plant residue in anoxic rice-field soil in Japan was characterized
      phenotypically and phylogenetically. Cells were Gram-negative, non-motile, non
      spore-forming, short rods. The strain utilized various sugars and produced
      propionate and acetate as major fermentation products with a small amount of
      succinate. The optimum growth temperature was 30 degrees C. Oxidase, catalase and
      nitrate-reducing activities were negative. The major cellular fatty acids were
      anteiso-C(15 : 0), C(15 : 0) and anteiso-C(17 : 0) 3-OH. Menaquinone MK-8(H4) was
      the major respiratory quinone. The genomic DNA G+C content was 39.3 mol%.
      Phylogenetic analysis based on the 16S rRNA gene sequence placed the strain in
      the phylum 'Bacteroidetes'. The closest relative to strain WB4T was an
      environmental clone from water contaminated with equine manure (sequence
      similarity of 99.7 %) and the strain formed a distinct cluster with other
      environmental clones mainly from freshwater sediments. The closest recognized
      species were members of the genus Dysgonomonas, with 16S rRNA gene sequence
      similarities of 90.9-89.8 %. Bacteroides merdae was the next closest recognized
      species (similarity of 88.7 % to the type strain). Given that the ecological,
      physiological and chemotaxonomic characteristics of strain WB4T were different
      from those of any related species, a new genus and species Paludibacter
      propionicigenes gen. nov., sp. nov., is proposed to accommodate it. The type
      strain is WB4T (= JCM 13257T = DSM 17365T).

PMID- 16403866
TI  - Belnapia moabensis gen. nov., sp. nov., an alphaproteobacterium from biological
      soil crusts in the Colorado Plateau, USA.
AB  - Strain CP2CT was isolated from biological soil crusts in the Colorado Plateau,
      USA. The isolate was aerobic, facultatively fermentative, Gram-negative, non
      motile and red-pigmented (due to the presence of carotenoids), but did not
      contain bacteriochlorophyll a. The strain tested positive for catalase, oxidase
      and urease and was negative for lysine and ornithine decarboxylases and arginine
      dihydrolase. The major fatty acids present were C(18 : 1)omega7c and C(16 : 0).
      It had a high DNA G+C content of 75 mol%. Comparisons of 16S rRNA gene sequences
      identified bacteriochlorophyll a-producing strains of Paracraurococcus ruber
      (94.9 %), Craurococcus roseus (92.2 %) and Roseococcus thiosulfatophilus (92.3
      %), as well as non-bacteriochlorophyll a-producing bacteria Muricoccus roseus
      (94.9 %), Roseomonas gilardii (94.2 %) and Roseomonas mucosa (93.8 %), as the
      bacteria most closely related to strain CP2CT. Phylogenetically, CP2CT was placed
      roughly equidistantly from the above organisms. Based on its phylogenetic
      placement and morphological and physiological characteristics, strain CP2CT is
      assigned to a new genus in the alpha-1 subgroup of the Proteobacteria, for which
      the name Belnapia gen. nov. is proposed. Strain CP2CT (= ATCC BAA-1043T = DSM
      16746T) is proposed as the type strain of the type species of this genus, with
      the name Belnapia moabensis gen. nov., sp. nov.

PMID- 16403865
TI  - Jannaschia seosinensis sp. nov., isolated from hypersaline water of a solar
      saltern in Korea.
AB  - A slightly halophilic alphaproteobacterium, designated CL-SP26T, was isolated
      from hypersaline water of a solar saltern located in Seosin, Korea. 16S rRNA gene
      sequence analysis revealed an affiliation with the genus Jannaschia. Sequence
      similarities between CL-SP26T and type strains of members of the genus Jannaschia
      were 94.9-97.2 %. Cells were rod-shaped and motile with one or more monopolar
      flagella. Strain CL-SP26T grew on solid media as circular red colonies. It was
      able to grow in 3-10 % sea salt; however, no growth occurred in media containing
      NaCl as the only salt. Strain CL-SP26T grew at 5-35 degrees C and pH 7-10. The
      major fatty acids were 18 : 1omega7c (64 %) and 18 : 0 (12.0 %). Three fatty
      acids, 3-OH 14 : 0/iso 16 : 1 (3.6 %), 18 : 3omega6c (2.2 %) and 10-methyl 19 : 0
      (1.9 %), found in minor quantities in CL-SP26(T), are unique among Jannaschia
      species. The DNA G+C content was 63 mol%. According to physiological data, fatty
      acid composition and 16S rRNA gene sequence analysis, CL-SP26T was assigned to
      the genus Jannaschia, but could be distinguished from recognized species of the
      genus. Strain CL-SP26T (= KCCM 42114T = JCM 13035T) therefore represents a novel
      species, for which the name Jannaschia seosinensis sp. nov. is proposed.

PMID- 16403868
TI  - Molecular evolution of the nif gene cluster carrying nifI1 and nifI2 genes in the
      Gram-positive phototrophic bacterium Heliobacterium chlorum.
AB  - A major nif cluster was detected in the strictly anaerobic, Gram-positive
      phototrophic bacterium Heliobacterium chlorum. The cluster consisted of 11 genes
      arranged within a 10 kb region in the order nifI1, nifI2, nifH, nifD, nifK, nifE,
      nifN, nifX, fdx, nifB and nifV. The phylogenetic position of Hbt. chlorum was the
      same in the NifH, NifD, NifK, NifE and NifN trees; Hbt. chlorum formed a cluster
      with Desulfitobacterium hafniense, the closest neighbour of heliobacteria based
      on the 16S rRNA phylogeny, and two species of the genus Geobacter belonging to
      the Deltaproteobacteria. Two nifI genes, known to occur in the nif clusters of
      methanogenic archaea between nifH and nifD, were found upstream of the nifH gene
      of Hbt. chlorum. The organization of the nif operon and the phylogeny of
      individual and concatenated gene products showed that the Hbt. chlorum nif operon
      carrying nifI genes upstream of the nifH gene was an intermediate between the nif
      operon with nifI downstream of nifH (group II and III of the nitrogenase
      classification) and the nif operon lacking nifI (group I). Thus, the phylogenetic
      position of Hbt. chlorum nitrogenase may reflect an evolutionary stage of a
      divergence of the two nitrogenase groups, with group I consisting of the aerobic
      diazotrophs and group II consisting of strictly anaerobic prokaryotes.

PMID- 16403867
TI  - Bacillus koreensis sp. nov., a spore-forming bacterium, isolated from the
      rhizosphere of willow roots in Korea.
AB  - An endospore-forming, rod-shaped bacterium was isolated from the rhizosphere of
      willow roots in Korea. The bacterium, designated strain BR030T, was a strictly
      aerobic, motile rod. The cell wall contained type A1gamma peptidoglycan with meso
      diaminopimelic acid as the diagnostic diamino acid. The major cellular fatty
      acids were anteiso-C(15 : 0), iso-C(15 : 0), iso-C(14 : 0) and iso-C(16 : 0). The
      major cellular phospholipids were phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and unknown phospholipids (PL1, PL2). The genomic DNA
      G+C content was 36 mol%. Comparative 16S rRNA gene sequence analyses showed that
      strain BR030T formed a distinct phyletic line within the genus Bacillus and was
      most closely related to Bacillus flexus DSM 1320T, with 16S rRNA gene sequence
      similarity of 96.8 %. Sequence similarities to other type strains were lower than
      96.2 %. On the basis of physiological and molecular properties, the isolate
      represents a novel species within the genus Bacillus, for which the name Bacillus
      koreensis sp. nov. is proposed. The type strain is BR030T (= KCTC 3914T = DSM
      16467T).

PMID- 16403869
TI  - Stappia marina sp. nov., a marine bacterium isolated from the Yellow Sea.
AB  - A Gram-negative, aerobic and halophilic bacterium designated strain mano18T was
      isolated from a tidal flat area of Dae-Chun, Chung-Nam, Korea. This strain was
      motile by means of polar flagella, occasionally forming rosette-like aggregates,
      reduced nitrate to nitrite, required sodium ions for growth, exhibited catalase
      and oxidase activities and contained Q-10 as the major quinone and C(18 :
      1)omega7c as the dominant cellular fatty acid. Analysis of the 16S rRNA gene
      sequence revealed that this strain is affiliated with a cluster within the
      Alphaproteobacteria. Strain mano18T synthesized bacteriochlorophyll under aerobic
      conditions. The 16S rRNA gene sequence similarity between strain mano18T and the
      most closely related species, Stappia aggregata DSM 13394T, was 98.5 %. Levels of
      DNA-DNA relatedness between strain mano18T and the type strains of S. aggregata
      and Stappia stellulata were respectively 6.2-11.2 and 3.3-7.6 %. Strain mano18T,
      like other Stappia strains, possesses carbon monoxide dehydrogenase genes. The
      results of DNA-DNA hybridization and the polyphasic data confirmed that strain
      mano18T can be considered to represent a novel taxon in the genus Stappia. The
      name Stappia marina sp. nov. is proposed for the tidal flat isolate; the type
      strain is strain mano18T (= KCTC 12288T = DSM 17023T).

PMID- 16403870
TI  - Stenotrophomonas koreensis sp. nov., isolated from compost in South Korea.
AB  - A Gram-negative, rod-shaped, non-spore-forming bacterium (TR6-01T) was isolated
      from compost near Daejeon city in South Korea. On the basis of 16S rRNA gene
      sequence similarity, strain TR6-01T was shown to belong to the class
      Gammaproteobacteria, related to Stenotrophomonas acidaminiphila (97.1 %) and
      Stenotrophomonas maltophilia (96.9 %); the phylogenetic distance from any other
      established species within the genus Stenotrophomonas was less than 97.0 %.
      Phenotypic and chemotaxonomic data (major ubiquinone Q-8; fatty acid profile)
      supported the affiliation of strain TR6-01T to the genus Stenotrophomonas. The
      results of DNA-DNA hybridization and physiological and biochemical tests allowed
      genotypic and phenotypic differentiation of strain TR6-01T from the five
      Stenotrophomonas species with validly published names. TR6-01T therefore
      represents a novel species, for which the name Stenotrophomonas koreensis sp.
      nov. is proposed, with the type strain TR6-01T (= KCTC 12211T = JCM 13256T).

PMID- 16403871
TI  - Sphingosinicella microcystinivorans gen. nov., sp. nov., a microcystin-degrading
      bacterium.
AB  - Three strains of bacteria that degrade the cyanobacterial hepatotoxin
      microcystin, Y2T, MDB2 and MDB3, were isolated from a eutrophic lake, Lake Suwa,
      and the Tenryu River, Japan, and characterized. These strains were aerobic and
      chemo-organotrophic and their cells were Gram-negative, non-spore-forming rods,
      motile by means of single polar flagella. Yellow-pigmented colonies were formed
      on nutrient agar media. The strains assimilated only citrate among the organic
      compounds tested as carbon sources. The G+C content of genomic DNA ranged from
      63.6 to 63.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the new isolates formed a tight cluster within the family
      Sphingomonadaceae but were clearly separate from established genera of this
      family, e.g. Sphingomonas, Sphingobium, Novosphingobium and Sphingopyxis;
      sequence similarities between the new isolates and type strains from established
      genera ranged from 90.9 to 94.9 %. Chemotaxonomic and phenotypic data supported
      the conclusion that these strains were members of the family Sphingomonadaceae.
      The major components of the cellular fatty acids were 18 : 1omega7c (36-41 %) and
      16 : 1omega7c (33-36 %). Hydroxy fatty acids were mainly 2-OH 14 : 0 (11-13 %),
      and 3-OH fatty acids were absent. Glycosphingolipids were detected. Ubiquinone-10
      and homospermidine were present as the major quinine and polyamine, respectively.
      Thus, it is proposed that the three strains represent a new genus and species of
      the family Sphingomonadaceae with the name Sphingosinicella microcystinivorans
      gen. nov., sp. nov. The type strain is Y2T (= KCTC 12019T = JCM 13185T).

PMID- 16403872
TI  - Mesorhizobium thiogangeticum sp. nov., a novel sulfur-oxidizing
      chemolithoautotroph from rhizosphere soil of an Indian tropical leguminous plant.
AB  - The bacterial strain SJT(T), along with 15 other mesophilic, neutrophilic and
      facultatively sulfur-oxidizing chemolithotrophic isolates, was isolated by
      enrichment on reduced sulfur compounds as the sole energy and electron source
      from soils immediately adjacent to the roots of Clitoria ternatea, a slender
      leguminous herb of the Lower Gangetic plains of India. Strain SJT(T) was able to
      oxidize thiosulfate and elemental sulfur for chemolithoautotrophic growth. 16S
      rRNA and recA gene sequence-based phylogenetic analyses showed that the Gram
      negative rod-shaped bacterium belonged to the genus Mesorhizobium and was most
      closely related to Mesorhizobium loti, Mesorhizobium plurifarium, Mesorhizobium
      amorphae and Mesorhizobium chacoense. Unequivocally low 16S rRNA (<97 %) and recA
      (< or =88 %) gene sequence similarities to all existing species of the most
      closely related genera, a unique fatty acid profile, a distinct G+C content (59.6
      mol%) and phenotypic characteristics all suggested that strain SJT(T) represents
      a novel species. DNA-DNA hybridization and SDS-PAGE analysis of whole-cell
      proteins also confirmed the taxonomic uniqueness of SJT(T). It is therefore
      proposed that isolate SJT(T) (= LMG 22697T = MTCC 7001T) be classified as the
      type strain of a novel species, Mesorhizobium thiogangeticum sp. nov.

PMID- 16403873
TI  - Molecular signatures in protein sequences that are characteristics of the phylum
      Aquificae.
AB  - Species of the phylum Aquificae are of great interest due to their strict extreme
      thermophilic growth characteristics. Presently, there is no known molecular
      characteristic which is unique to this group of bacteria. This work describes six
      conserved inserts and deletions (indels or signature sequences) in four widely
      distributed proteins that are distinctive features of species from the phylum
      Aquificae. These include three signatures consisting of a 2 aa insert, a 5-6 aa
      insert and a 6 aa deletion in DNA polymerase I (PolA), a 6-7 aa insert in glucose
      inhibited protein A (GidA), a 52 aa insert in the RNA polymerase beta'-subunit
      (RpoC) and a 4 aa insert in elongation factor Tu (EF-Tu). Fragments of these
      genes were amplified in most cases from Hydrogenobacter hydrogenophilus,
      Hydrogenothermus marinus and Thermocrinis ruber and combined with available
      sequence data from 'Aquifex aeolicus' and Sulfurihydrogenibium azorense. The
      presence of the PolA, GidA and RpoC indels in all of the species sequenced
      provides evidence that they are probably distinctive characteristics of the
      entire phylum. The indel in EF-Tu, which is shared by Aquifex species and
      Hydrogenobacter but not Hydrogenothermus and Sulfurihydrogenibium, may provide a
      molecular marker for the family Aquificaceae. We have also identified a 51 aa
      insert in SecA preprotein translocase that is commonly shared by various species
      of the Aquificae as well as two Thermotoga species (Thermotoga maritima and
      Thermotoga neapolitana) which may be due to lateral gene transfer between these
      groups. In phylogenetic trees based on a concatenated dataset of fragments from
      eight different proteins as well as 16S rRNA, the observed branching pattern of
      these species was very similar and it was consistent with the relationships
      inferred from various indels. The identified indels provide a novel means for
      distinguishing species of the Aquificae from all other bacteria in molecular
      terms and may prove useful for functional studies aimed at understanding the
      unique biochemical and physiological characteristics of the Aquificae.

PMID- 16403874
TI  - Methylobacter tundripaludum sp. nov., a methane-oxidizing bacterium from Arctic
      wetland soil on the Svalbard islands, Norway (78 degrees N).
AB  - A Gram-negative, rod-shaped, non-motile, non-spore forming bacterium (SV96T) was
      isolated from wetland soil near Ny-Alesund, Svalbard. On the basis of 16S rRNA
      gene sequence similarity, strain SV96T was shown to belong to the
      Gammaproteobacteria, related to Methylobacter psychrophilus Z-0021T (99.1 %),
      Methylobacter luteus ATCC 49878T (97.3 %), Methylobacter marinus A45T (97.0 %)
      and Methylobacter whittenburyi ATCC 51738T (95.8 %); the closest related species
      within the genus Methylomicrobium with a validly published name was
      Methylomicrobium album ATCC 33003T (95.0 %). Chemotaxonomic data (including the
      major fatty acids: 16 : 1omega8, 16 : 1omega7 and 16 : 1omega5t) supported the
      affiliation of strain SV96T to the genus Methylobacter. The results of DNA-DNA
      hybridization, physiological and biochemical tests allowed genotypic and
      phenotypic differentiation of strain SV96T from the four Methylobacter species
      mentioned above. Strain SV96T therefore represents a novel species, for which the
      name Methylobacter tundripaludum sp. nov. is proposed (type strain SV96T = DSM
      17260T = ATCC BAA-1195T).

PMID- 16403875
TI  - Gaetbulimicrobium brevivitae gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae isolated from a tidal flat of the Yellow Sea in Korea.
AB  - A Gram-negative, non-spore-forming and rod-shaped gliding bacterium, designated
      strain SMK-19T, was isolated from a tidal flat sediment of the Yellow Sea, Korea,
      and its taxonomic position was investigated by using a polyphasic approach.
      Strain SMK-19T grew optimally at 37 degrees C, in the presence of 2-3 % (w/v)
      NaCl and at pH 7.0-8.0. It contained MK-6 as the predominant menaquinone, and iso
      C(17 : 0) 3-OH and iso-C(15 : 0) as the major fatty acids. Major polar lipids
      were phosphatidylethanolamine, unidentified phospholipids and an amino-group
      containing lipid that is ninhydrin-positive. The DNA G+C content was 36.0 mol%.
      Phylogenetic analyses based on 16S rRNA gene sequences demonstrated that strain
      SMK-19T formed a distinct evolutionary lineage within the family
      Flavobacteriaceae. The 16S rRNA gene sequence of strain SMK-19T exhibited
      similarity values of <94.4 % to those of other members of the family
      Flavobacteriaceae. Strain SMK-19T was distinguished from phylogenetically related
      genera by differences in several phenotypic properties. On the basis of
      phenotypic, phylogenetic and chemotaxonomic data, SMK-19T (= KCTC 12390T = DSM
      17196T) was classified at the type strain of a novel genus and species,
      Gaetbulimicrobium brevivitae gen. nov., sp. nov.

PMID- 16403876
TI  - Polyphasic study of Zymomonas mobilis strains revealing the existence of a novel
      subspecies Z. mobilis subsp. francensis subsp. nov., isolated from French cider.
AB  - Zymomonas mobilis strains recently isolated from French 'framboise' ciders were
      compared with collection strains of the two defined subspecies, Z. mobilis subsp.
      mobilis and Z. mobilis subsp. pomaceae, using a polyphasic approach. Six strains
      isolated from six different regions of France were compared with three strains of
      Z. mobilis subsp. mobilis, including the type strain LMG 404T, and four strains
      of Z. mobilis subsp. pomaceae, including the type strain LMG 448T, using
      phenotypic and genotypic methods. For phenotypic characterization, both
      physiological tests and SDS-PAGE protein profiles revealed significant
      differences between the two known subspecies and the French isolates; three
      distinct groups were observed. These findings were further confirmed by random
      amplified polymorphic DNA and repetitive extragenic palindromic-PCR genotyping
      methods in which the French isolates were clearly distinguished from the other
      two subspecies. Sequence analysis of a fragment ranging from 604 to 617
      nucleotides corresponding to the 16S-23S rRNA gene intergenic spacer region
      (ISR), a 592 nucleotide HSP60 gene fragment and a 1044 nucleotide gyrB gene
      fragment confirmed the presence of three distinct groups. The French strains
      exhibited almost 94 % similarity to the ISR, 90 % to HSP60 and 86 % to gyrB
      sequences of the three collection strains of Z. mobilis subsp. mobilis and 87, 84
      and 80 % sequence similarity, respectively, was observed with the four Z. mobilis
      subsp. pomaceae strains. Based on both the phenotypic and genotypic results, the
      French strains are proposed to represent a novel subspecies, Zymomonas mobilis
      subsp. francensis subsp. nov. Strain AN0101T (= LMG 22974T = CIP 108684T) was
      designated as the type strain.

PMID- 16403877
TI  - Methanosaeta harundinacea sp. nov., a novel acetate-scavenging methanogen
      isolated from a UASB reactor.
AB  - Two methanogenic strains, 8AcT and 6Ac, were isolated from an upflow anaerobic
      sludge blanket reactor treating beer-manufacture wastewater in Beijing, China.
      Cells of strains 8AcT and 6Ac were rod-shaped (0.8-1.0 x 3-5 microm) and non
      motile, occurring singly or in pairs; however, at high cell density the cells
      were arranged in long chains within a common sheath. The two strains used acetate
      exclusively for growth and methane production. The specific growth rate of strain
      8AcT was 0.030 h(-1) when growing in acetate (20 mM) at 37 degrees C. The
      temperature range for growth was 25-45 degrees C, with the fastest growth at 34
      37 degrees C. The pH range for growth and methane production was 6.5-9.0, with
      the fastest growth at pH 7.2-7.6. The G+C content of genomic DNA of strain 8AcT
      was 55.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequence similarity
      showed that the novel strains clustered with Methanosaeta species; the 16S rRNA
      gene sequence similarities between strain 8AcT and Methanosaeta concilii DSM 3013
      and 'Methanosaeta thermophila' DSM 6194 were 92.5 and 87.3 %, respectively. The
      sequence similarity levels of mcrA, the gene encoding the alpha-subunit of methyl
      coenzyme M reductase, and of the deduced amino acids of mcrA, between strain 8AcT
      and Methanosaeta concilii DSM 3671T were 36 and 78.9 %, respectively. Based on
      the phylogenetic and phenotypic analyses, the novel species Methanosaeta
      harundinacea sp. nov. is proposed, with strain 8AcT (= JCM 13211T = CGMCC
      1.5026T) as the type strain.

PMID- 16403878
TI  - rpoB gene sequence-based characterization of emerging non-tuberculous
      mycobacteria with descriptions of Mycobacterium bolletii sp. nov., Mycobacterium
      phocaicum sp. nov. and Mycobacterium aubagnense sp. nov.
AB  - Over the past 10 years, 16S rRNA gene sequencing has contributed to the
      establishment of more than 45 novel species of non-tuberculous mycobacteria and
      to the description of emerging mycobacterial infections. Cumulative experience
      has indicated that this molecular tool underestimates the diversity of this group
      and does not distinguish between all recognized mycobacterial taxa. In order to
      improve the recognition of emerging rapidly growing mycobacteria (RGM), rpoB gene
      sequencing has been developed. Our previous studies have shown that an RGM
      isolate is a member of a novel species if it exhibits >3 % sequence divergence in
      the rpoB gene from the type strains of established species. When applied to a
      collection of 59 clinical RGM isolates, rpoB gene sequencing revealed nine novel
      isolates (15.3 %) whereas only two isolates (3.4 %) were deemed to be novel by
      conventional 16S rRNA gene sequence analysis. A polyphasic approach, including
      biochemical tests, antimicrobial susceptibility analyses, hsp65, sodA and recA
      gene sequence analysis, DNA G+C content determination and cell-wall fatty acid
      composition analysis, supported the evidence that these nine isolates represent
      three novel species. Whereas Mycobacterium phocaicum sp. nov. (type strain N4T =
      CIP 108542T = CCUG 50185T) and Mycobacterium aubagnense sp. nov. (type strain U8T
      = CIP 108543T = CCUG 50186T; Mycobacterium mucogenicum group) were susceptible to
      most antibiotics, Mycobacterium bolletii sp. nov. (type strain BD(T) = CIP
      108541T = CCUG 50184T; Mycobacterium chelonae-abscessus group) was resistant to
      the quinolones, tetracycline, macrolides and imipenem. Only M. bolletii was
      resistant to clarithromycin. These data illustrate that rpoB gene sequence-based
      identification is a powerful tool to characterize emerging RGM and mycobacterial
      infections and provides valuable help in differentiating RGM at both the intra-
      and interspecies level, thus contributing to a faster and more efficient
      diagnosis and epidemiological follow-up.

PMID- 16403879
TI  - Dokdonella koreensis gen. nov., sp. nov., isolated from soil.
AB  - Two Gram-negative, motile, non-spore-forming and rod-shaped bacterial strains, DS
      123T and DS-140, were isolated from soil and their taxonomic positions were
      investigated by a polyphasic study. Strains DS-123T and DS-140 grew optimally at
      30 degrees C and pH 6.5 without NaCl. They contained Q-8 as the predominant
      ubiquione and iso-C(17 : 1)omega9c, iso-C(17 : 0) and iso-C(15 : 0) as the major
      fatty acids. Major polar lipids detected in the two strains were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an
      amino-group-containing lipid that was ninhydrin-positive. Their DNA G+C contents
      were 71.0 mol%. Strains DS-123T and DS-140 exhibited no difference in their 16S
      rRNA gene sequences and possessed a mean DNA-DNA relatedness level of 92 %.
      Phylogenetic trees based on 16S rRNA gene sequences showed that strains DS-123T
      and DS-140 formed a distinct evolutionary lineage within the Gammaproteobacteria.
      The 16S rRNA gene sequences of strains DS-123T and DS-140 exhibited similarity
      values of less than 94.1 % to members of the Gammaproteobacteria. Strains DS-123T
      and DS-140 were distinguished from phylogenetically related genera by differences
      in some phenotypic properties. On the basis of phenotypic, phylogenetic and
      genetic data, it is proposed that strains DS-123T (= KCTC 12396T = DSM 17203T)
      and DS-140 be classified in a novel genus and species, Dokdonella koreensis gen.
      nov., sp. nov.

PMID- 16403880
TI  - Bacteroides intestinalis sp. nov., isolated from human faeces.
AB  - During studies of the microbiota of human faeces, five strains of Gram-negative
      anaerobic rods were isolated following growth in a polyamine-deficient medium.
      These strains belonged to the genus Bacteroides on the basis of 16S rRNA gene
      sequence data. 16S rRNA gene sequence similarity between one of the strains,
      341T, and recognized species within the genus Bacteroides was <95 %. The DNA G+C
      content (44 mol%) and major fatty acid composition (anteiso-C(15 : 0), 32.0 %)
      supported the affiliation of strain 341(T) to the genus Bacteroides. Biochemical
      tests and DNA-DNA hybridization analysis demonstrated that strain 341T was
      distinct from Bacteroides uniformis and Bacteroides helcogenes, to which it was
      related most closely. On the basis of these data, a novel Bacteroides species,
      Bacteroides intestinalis sp. nov., is proposed with strain 341T (= JCM 13265T =
      DSM 17393T) as the type strain.

PMID- 16403881
TI  - Arenibacter palladensis sp. nov., a novel marine bacterium isolated from the
      green alga Ulva fenestrata, and emended description of the genus Arenibacter.
AB  - The taxonomic position of three novel, marine, heterotrophic, aerobic, pigmented,
      gliding bacteria, isolated from the green alga Ulva fenestrata in the Sea of
      Japan, was determined. 16S rRNA gene sequence analysis revealed that the strains
      belong to the genus Arenibacter. The results of DNA-DNA hybridization experiments
      supported by phenotypic and chemotaxonomic data showed that the isolates
      represent a novel species of the genus Arenibacter, for which the name
      Arenibacter palladensis sp. nov. is proposed. The type strain is KMM 3961T (= LMG
      21972T = CIP 108849T).

PMID- 16403882
TI  - Formosa agariphila sp. nov., a budding bacterium of the family Flavobacteriaceae
      isolated from marine environments, and emended description of the genus Formosa.
AB  - Two marine, heterotrophic, aerobic, yellow-pigmented, agarolytic bacterial
      strains that are motile by means of gliding were isolated from the green alga
      Acrosiphonia sonderi and from sea water. Comparative 16S rRNA gene sequence
      analysis revealed an affiliation between the strains studied and the genus
      Formosa, a member of the family Flavobacteriaceae. The level of sequence
      similarity between strain KMM 3901T and Formosa algae KMM 3553T was 99.1 %. The
      results of DNA-DNA hybridization experiments and phenotypic analysis indicated
      that the strains represent a novel species of the genus Formosa, for which the
      name Formosa agariphila sp. nov. is proposed, with KMM 3901T (= KCTC 12365T = LMG
      23005T = DSM 15362T) as the type strain. The description of the genus Formosa is
      emended with newly obtained data.

PMID- 16403883
TI  - Culturable phylogenetic diversity of the phylum 'Bacteroidetes' from river
      epilithon and coastal water and description of novel members of the family
      Flavobacteriaceae: Epilithonimonas tenax gen. nov., sp. nov. and Persicivirga
      xylanidelens gen. nov., sp. nov.
AB  - Members of the phylum 'Bacteroidetes' are important heterotrophs involved in
      cycling organic carbon in aquatic habitats. Their diversity has been studied by
      molecular methods in both freshwater and marine habitats and many novel genera
      and species within this phylum have been characterized in recent years. In this
      study, we examined the diversity of members of the 'Bacteroidetes' that could be
      readily isolated on solid media from river epilithon and coastal sea water. Most
      (93 %) of the 55 isolates confirmed as members of the 'Bacteroidetes' and
      examined by phylogenetic analysis of 16S rRNA gene sequences belonged to the
      Flavobacteriaceae. Furthermore, most (62 %) of these were almost certainly
      members of the genus Flavobacterium and all but one were from river epilithon.
      Conversely, the sea-water isolates were more widely distributed in clades
      containing other genera. Some of the isolates were deep-branching within
      phylogenetic trees and so could not be assigned to putative genera. Two of these
      deep-branching isolates were characterized by polyphasic taxonomy and are
      proposed as novel species within two new genera of the family Flavobacteriaceae.
      These are Epilithonimonas tenax gen. nov., sp. nov. (type strain EP105T = NCIMB
      14026T = DSM 16811T) and Persicivirga xylanidelens gen. nov., sp. nov. (type
      strain SW256T = NCIMB 14027T = DSM 16809T).

PMID- 16403884
TI  - Stenothermobacter spongiae gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae isolated from a marine sponge in the Bahamas, and emended
      description of Nonlabens tegetincola.
AB  - A bacterial strain, UST030701-156T, was isolated from a marine sponge in the
      Bahamas. Strain UST030701-156T was orange-pigmented, Gram-negative, rod-shaped
      with tapered ends, slowly motile by gliding and strictly aerobic. The predominant
      fatty acids were a15 : 0, i15 : 0, i15 : 0 3-OH, i17 : 0 3-OH, i17 : 1omega9c and
      summed feature 3, comprising i15 : 0 2-OH and/or 16 : 1omega7c. MK-6 was the only
      respiratory quinone. Flexirubin-type pigments were not produced. Phylogenetic
      analysis based on 16S rRNA gene sequences placed UST030701-156T within a distinct
      lineage in the family Flavobacteriaceae, with 93.3 % sequence similarity to the
      nearest neighbour, Nonlabens tegetincola. The DNA G+C content of UST030701-156T
      was 41.0 mol% and was much higher than that of N. tegetincola (33.6 mol%). Strain
      UST030701-156T can be distinguished from other members of the Flavobacteriaceae
      by means of a number of chemotaxonomic and phenotypic characteristics. It is
      proposed, therefore, that UST030701-156T represents a novel taxon designated
      Stenothermobacter spongiae gen. nov., sp. nov. The type strain is UST030701-156T
      (= NRRL B-41138T = JCM 13191T). Carbon-source utilization by N. tegetincola was
      re-examined and an emended description is therefore included.

PMID- 16403885
TI  - Donghaeana dokdonensis gen. nov., sp. nov., isolated from sea water.
AB  - A Gram-negative, non-motile, non-spore-forming and rod-shaped bacterial strain,
      DSW-6T, was isolated from sea water and subjected to a polyphasic study. Strain
      DSW-6T grew optimally at 25 degrees C, in the presence of 2 % (w/v) NaCl and at
      pH 7.0-8.0. It was characterized chemotaxonomically as having MK-6 as the
      predominant menaquinone and iso-C(15 : 0), anteiso-C(15 : 0), iso-C(17 : 0) 3-OH
      and C(15 : 0) as the major fatty acids (>10 % of total fatty acids). Major polar
      lipids were phosphatidylethanolamine, unidentified phospholipids and amino-group
      containing lipids that are ninhydrin-positive. The DNA G+C content was 36.9 mol%.
      Phylogenetic analyses based on 16S rRNA gene sequences showed that strain DSW
      6(T) forms an independent line of descent within the family Flavobacteriaceae.
      The 16S rRNA gene sequence of strain DSW-6T exhibited similarity values of less
      than 94.7 % to the sequences of other members of the family Flavobacteriaceae.
      Strain DSW-6T could be distinguished from other phylogenetically related genera
      by differences in several phenotypic properties. Therefore, in view of the
      combined phenotypic and phylogenetic data, it is proposed that strain DSW-6T (=
      KCTC 12402T = DSM 17205T) represents a novel genus and species, Donghaeana
      dokdonensis gen. nov., sp. nov.

PMID- 16403886
TI  - Williamsia deligens sp. nov., isolated from human blood.
AB  - The taxonomic status of two bacterial strains isolated from human blood was
      characterized using a polyphasic approach. Chemotaxonomic investigations revealed
      the presence of cell-wall chemotype IV, short-chain mycolic acids that co
      migrated with those extracted from members of the genus Williamsia and that
      produce C(16 : 0) and C(18 : 0) fatty acids on pyrolysis GC, and dihydrogenated
      menaquinone with nine isoprene units as the predominant isoprenologue. The
      generic assignment was confirmed by 16S rRNA gene sequencing. Comparative
      analysis of the 16S rRNA gene sequence showed that these isolates constitute a
      distinct phyletic line within the genus Williamsia, displaying 96.2 and 97.2 %
      sequence similarities to Williamsia muralis and Williamsia maris, respectively.
      The two isolates could be distinguished from the type strains of the latter
      species on the basis of several phenotypic traits. The genotypic and phenotypic
      data show that the strains merit classification as a novel species of Williamsia,
      for which the name Williamsia deligens sp. nov. is proposed, with type strain
      IMMIB RIV-956T (= DSM 44902T = CCUG 50873T).

PMID- 16403887
TI  - Reclassification of Amycolatopsis orientalis DSM 43387 as Amycolatopsis
      benzoatilytica sp. nov.
AB  - Amycolatopsis orientalis DSM 43387, a clinical isolate from submandibular
      mycetoma tissue, is one of three plasmid-bearing strains of the genus
      Amycolatopsis. It degrades aromatic compounds such as m-hydroxybenzoate, but does
      not produce any antibiotics, in contrast to Amycolatopsis orientalis NBRC 12806T.
      Phylogenetic analysis based on a complete 16S rRNA gene sequence placed the
      strain in the clade of Amycolatopsis albidoflavus IMSNU 22139T, distant from the
      clade of A. orientalis NBRC 12806T. The strain showed low DNA-DNA hybridization
      values of 24.1 and 45.7 % with A. orientalis NBRC 12806T and A. albidoflavus DSM
      44639T (= IMSNU 22139T), respectively. It could also be readily distinguished
      from A. orientalis NBRC 12806T and all species with validly published names
      classified in the genus Amycolatopsis, by using a combination of chemical and
      physiological markers such as utilization of lactose, degradation of xanthine,
      hypoxanthine, gelatin and casein and hydrolysis of Tween 80, indicating that it
      represents a novel species. Strain DSM 43387 could also be differentiated from A.
      orientalis NBRC 12806T and its nearest neighbour A. albidoflavus IMSNU 22139T on
      the basis of fatty acid and phospholipid profiles. Based on genotypic and
      phenotypic differences, the name Amycolatopsis benzoatilytica sp. nov. is
      proposed for strain DSM 43387 that was previously classified as Amycolatopsis
      orientalis. The type strain is AK 16/65T (= DSM 43387T = ATCC 55165T = IMRU
      1389T).

PMID- 16403888
TI  - Shewanella halifaxensis sp. nov., a novel obligately respiratory and denitrifying
      psychrophile.
AB  - Indigenous bacteria found in the sediment of the Emerald Basin (depth of 215 m,
      Atlantic Ocean) located offshore of Halifax Harbour (Nova Scotia, Canada) were
      previously found to be able to degrade the explosive compound hexahydro-1,3,5
      trinitro-1,3,5-triazine (RDX). In the present study, a novel obligately
      respiratory, denitrifying and RDX-mineralizing bacterium, designated strain HAW
      EB4(T), was isolated from the marine sediment. This bacterium utilized peptone,
      yeast extract, Casamino acids, esters (Tweens 20, 40 and 80), sugars (N-acetyl-D
      glucosamine, ribose), several C2 and C3 acids (acetate, pyruvate, lactate,
      propionate) and amino acids (serine, proline) as sole carbon and energy sources.
      Aerobically grown cells (in marine broth 2216 at 10 degrees C) contained C(14 :
      0) (6 %), iso-C(15 : 0) (12 %), C(16 : 0) (20 %), C(16 : 1)omega7 (37 %), C(18 :
      1)omega7 (7 %) and C(20 : 5)omega3 (7 %) as major membrane fatty acids, and Q7
      (28.1 %) and MK-7 (60.9 %) as dominant respiratory quinones, consistent with deep
      sea species of Shewanella. The novel bacterium had a DNA G+C content of 45 mol%
      and showed similarity to Shewanella species in terms of 16S rRNA and gyrB gene
      sequences (93-99 and 67.3-88.4 % similarity, respectively), with Shewanella
      pealeana being the most closely related species. Genomic DNA-DNA hybridization
      between strain HAW-EB4T and S. pealeana revealed a level of relatedness of 17.9
      %, lower than the 70 % species cut-off value, indicating that strain HAW-EB4T (=
      NCIMB 14093T = DSM 17350T) is the type strain of a novel species of Shewanella,
      for which the name Shewanella halifaxensis sp. nov. is proposed.

PMID- 16403889
TI  - Reclassification of Leuconostoc argentinum as a later synonym of Leuconostoc
      lactis.
AB  - Leuconostoc argentinum, Leuconostoc lactis and ten related strains from Romanian
      dairy products formed a single cluster, clearly separated from other Leuconostoc
      species, after numerical analysis of repetitive extragenic palindromic-PCR
      patterns, whole-cell protein profiles (SDS-PAGE) and fluorescent amplified
      fragment length polymorphism (FAFLP) band patterns. 16S rRNA gene sequence
      analysis confirmed a very high similarity between both type strains and
      representative dairy isolates (>99.6 %). DNA-DNA hybridization experiments
      revealed high relatedness values between the type strains of L. argentinum and L.
      lactis and between these strains and representative Romanian strains. These data
      and the lack of phenotypic distinctive characteristics demonstrate that L.
      argentinum and L. lactis are synonymous.

PMID- 16403890
TI  - RFLP analysis of the rRNA operon of a Brazilian collection of bradyrhizobial
      strains from 33 legume species.
AB  - Genetic diversity in tropical rhizobial species is still poorly known. With the
      aim of increasing this knowledge, three ribosomal regions of 119 strains
      belonging to the official Brazilian culture collection of rhizobia and classified
      as Bradyrhizobium based on morphological and physiological characteristics in
      vitro were analysed by RFLP-PCR. The strains were isolated from 33 legume
      species, representing nine tribes and all three subfamilies; they all form very
      effective N2-fixing nodules and 43 of them are recommended for use in Brazilian
      commercial inoculants as the most effective for their hosts. For the 16S rRNA
      gene, type and reference strains of Bradyrhizobium japonicum fell into two major
      clusters, joined at a level of similarity of 50 %, which included 52 strains, 90
      % of which were isolated from soybean. Two other clusters, joined at a similarity
      of 53 %, included reference strains of Bradyrhizobium elkanii, but not USDA 76T;
      furthermore, two other major clusters were identified and all strains were
      clustered at a final level of similarity of only 28 %. For the intergenic spacer
      (IGS) between genes coding for the 16S and 23S rRNA, strains were clustered at a
      final level of similarity of 27 %. Reference strains of B. japonicum fell into a
      major group with 51 strains, 84 % isolated from soybean, with a similarity of 59
      %, while strains of B. elkanii fell into another major group, with a similarity
      of 55 %, clustering 44 strains, 59 % of which were isolated from hosts other than
      soybean. New clusters were also observed for the IGS region. The largest number
      of differences was detected in the analysis of the 23S rRNA gene, and 16 groups
      and isolated strains were joined at a very low level of similarity (16 %). In a
      combined analysis with the three ribosomal regions, the majority of strains
      isolated from soybean clustered with a similarity of 54 % with type and reference
      strains of B. japonicum, while most strains isolated from Brazilian indigenous
      legume species grouped with B. elkanii at a level of similarity of 46 %. All
      strains were clustered at a very low level of similarity (27 %), and at least two
      new clusters were clearly defined. These new clusters might be related to
      intraspecific differences or to novel subspecies, or even to novel species;
      indeed, strains from one of these clusters show higher 16S rRNA gene sequence
      similarity to members of the genus Burkholderia. The results obtained in this
      study emphasize the high level of diversity of symbiotic diazotrophic bacteria in
      the tropics that still remains to be determined.

PMID- 16403891
TI  - Lysobacter koreensis sp. nov., isolated from a ginseng field.
AB  - Strain Dae16T, a Gram-negative, non-spore-forming, rod-shaped bacterium, was
      isolated from the soil of a ginseng field in South Korea and characterized in
      order to determine its taxonomic position. 16S rRNA gene sequence analysis
      revealed that strain Dae16T belongs to the Gammaproteobacteria and had the
      highest degree of sequence similarity to Lysobacter gummosus ATCC 29489T (97.1
      %), Lysobacter antibioticus DSM 2044T (96.6 %), Lysobacter enzymogenes DSM 2043T
      (96.2 %), Lysobacter concretionis KCTC 12205T (94.7 %) and Lysobacter brunescens
      ATCC 29482T (93.7 %). Chemotaxonomic data revealed that strain Dae16T possesses a
      quinone system with Q-8 as the predominant compound and C(15 : 0) iso, C(16 : 0)
      iso and C(17 : 1) iso omega9c as the predominant iso-branched fatty acids, all of
      which corroborated the assignment of the strain to the genus Lysobacter. Results
      of DNA-DNA hybridization and physiological and biochemical tests clearly
      demonstrated that strain Dae16T represents a distinct species. Based on these
      data, it is proposed that Dae16T (= KCTC 12204T = NBRC 101156T) should be
      classified as the type strain of a novel Lysobacter species, Lysobacter koreensis
      sp. nov.

PMID- 16403892
TI  - Larkinella insperata gen. nov., sp. nov., a bacterium of the phylum
      'Bacteroidetes' isolated from water of a steam generator.
AB  - A Gram-negative bacterium, designated strain LMG 22510T, was isolated from water
      of a pharmaceutical company steam generator. The cells had a ring-like and
      horseshoe-shaped morphology and possessed gliding motility. Phylogenetic analysis
      of the 16S rRNA gene sequence showed that the strain was a member of the
      Flexibacter group within the phylum 'Bacteroidetes'; its nearest neighbour was
      Spirosoma linguale (88.8 % sequence similarity). DNA base content, fatty acid
      composition and biochemical characteristics were determined. Genotypic and
      phenotypic data indicated that strain LMG 22510T could not be assigned to any
      recognized genus; therefore, a novel genus and species is proposed, Larkinella
      insperata gen. nov., sp. nov., with LMG 22510T (= NCIMB 14103T) as the type
      strain.

PMID- 16403893
TI  - Shewanella hafniensis sp. nov. and Shewanella morhuae sp. nov., isolated from
      marine fish of the Baltic Sea.
AB  - Two novel species belonging to the genus Shewanella are described on the basis of
      their phenotypic characteristics, phylogenetic analyses of 16S rRNA and gyrB gene
      sequences and levels of DNA-DNA hybridization. A total of 47 strains belonging to
      two novel Gram-negative, psychrotolerant, H2S-producing bacterial species were
      isolated from marine fish (cod and flounder) caught from the Baltic Sea off
      Denmark. The phenotypic characteristics of strains belonging to group 1 (14
      strains) indicated that these represented a non-sucrose-assimilating variant of
      Shewanella baltica with a DNA G+C content of 47.0 mol%. Strains of group 2 (33
      isolates) did not utilize the carbon substrates assimilated by S. baltica except
      gluconate, N-acetylglucosamine and malate. Their DNA G+C content was 44.0 mol%.
      Phylogenetic analysis of the 16S rRNA gene sequence data placed the two novel
      species within the genus Shewanella. Group 1 strains showed greatest sequence
      similarity to Shewanella putrefaciens ATCC 8071T (99.0 %) and with S. baltica
      NCTC 10375(T) (98.3 %). However, gyrB gene sequence analysis showed these
      isolates to share only 90.0 % sequence similarity with S. putrefaciens ATCC 8071T
      and 93.9 % with S. baltica NCTC 10375T. Similarly, DNA-DNA hybridization
      experiments revealed DNA relatedness levels of 38 % between the group 1 isolates
      and S. putrefaciens ATCC 8071T and 43 % with S. baltica NCTC 10375T. The group 2
      strains shared less than 97 % 16S rRNA gene sequence similarities with recognized
      Shewanella species. Comparisons between the two novel species indicated 16S rRNA
      gene sequence similarity of approximately 98 %, gyrB gene sequence similarity of
      approximately 89 % and DNA-DNA reassociation values of 20-34 %. Based on the
      evidence presented, two novel species, Shewanella hafniensis sp. nov. (type
      strain P010T = ATCC BAA-1207T = NBRC 100975T) and Shewanella morhuae sp. nov.
      (type strain U1417T = ATCC BAA-1205T = NBRC 100978T), are described.

PMID- 16403894
TI  - Virgibacillus koreensis sp. nov., a novel bacterium from a salt field, and
      transfer of Virgibacillus picturae to the genus Oceanobacillus as Oceanobacillus
      picturae comb. nov. with emended descriptions.
AB  - A novel Virgibacillus strain, BH30097T, was isolated from a salt field near Taean
      Gun on the Yellow Sea in Korea. Cells were Gram-positive rods and bore
      ellipsoidal endospores in terminal positions. The optimum pH and temperature for
      growth of this organism were pH 7 and 25 degrees C, respectively. The main
      respiratory quinone was MK-7 and the major cellular fatty acids were anteiso-C(15
      : 0) and iso-C(16 : 0). Analysis based on 16S rRNA gene sequence data revealed
      that the isolate formed an evolutionary lineage distinct from other Virgibacillus
      species. Levels of sequence similarity between the isolate and other
      Virgibacillus species ranged from 93.8 to 96.7 %. DNA-DNA relatedness values
      between strain BH30097T and a phylogenetically closely related strain,
      Virgibacillus halodenitrificans KCTC 3790T, were less than 24 %. On the basis of
      morphological, physiological and chemotaxonomic characteristics, 16S rRNA gene
      sequence comparison and DNA-DNA hybridization, a novel species, Virgibacillus
      koreensis sp. nov., is proposed, with the type strain BH30097T (= KCTC 3823T =
      JCM 12387T). It is also proposed that Virgibacillus picturae be transferred to
      the genus Oceanobacillus as Oceanobacillus picturae comb. nov. based on its 16S
      rRNA gene sequences and other taxonomic characteristics.

PMID- 16403895
TI  - Actinomadura hallensis sp. nov., a novel actinomycete isolated from Mt. Halla in
      Korea.
AB  - A novel actinomycete, strain H647-1T, which was isolated from soil of Mt. Halla,
      Jeju Island, Republic of Korea, was subjected to phenotypic and genotypic
      characterization. The organism, which produces warty spore chains arranged in
      hooks or spirals on the aerial mycelium, was shown to have chemotaxonomic
      characteristics consistent with assignment to the genus Actinomadura. A
      comparative analysis of 16S rRNA gene sequences indicated that the organism
      formed a distinct clade within the evolutionary radiation of the family
      Thermomonosporaceae and that it was closely associated with members of the genus
      Actinomadura, but possessed a 22 nt extended loop between positions 453 and 479
      of the 16S rRNA gene sequence (Escherichia coli numbering). A broad range of
      phenotypic and genetic data supported the suggestion that this organism
      represents a novel species of the genus Actinomadura, for which the name
      Actinomadura hallensis sp. nov. is proposed. The type strain is strain H647-1T (=
      IMSNU 50760T = KCTC 9992T = KCCM 42245T = NRRL B-24436T).

PMID- 16403896
TI  - Amycolatopsis minnesotensis sp. nov., isolated from a prairie soil.
AB  - Two actinomycete strains, 32U-2T and 32U-4, were isolated from a prairie soil in
      Minnesota and subjected to characterization by means of polyphasic taxonomy. The
      16S rRNA gene sequences were determined following PCR amplification and cloning.
      A phylogenetic analysis, based on comparative analysis of 16S rRNA gene
      sequences, indicated that the organisms consistently formed a well-separated,
      distinct sub-branch within the radiation of the genus Amycolatopsis of the family
      Pseudonocardiaceae. The levels of 16S rRNA sequence similarity between the
      isolates and the type strains of recognized Amycolatopsis species ranged from
      94.1 to 97.9 %. The highest levels of sequence similarity were found between the
      isolates and Amycolatopsis coloradensis (97.6-97.9 %), Amycolatopsis alba and
      Amycolatopsis orientalis (97.3-97.6 %) and Amycolatopsis lurida (97.2-97.5 %).
      Chemotaxonomic characteristics supported the phylogenetic relationships between
      the organisms and members of the genus Amycolatopsis. However, a broad range of
      phenotypic and genetic data revealed that the isolates should be classified as
      novel species of the genus Amycolatopsis, for which the name Amycolatopsis
      minnesotensis sp. nov. is proposed. The type strain is 32U-2T (=KCCM 42246T =
      NRRL B-24435T).

PMID- 16403897
TI  - Nocardioides lentus sp. nov., isolated from an alkaline soil.
AB  - Gram-positive, rod- or coccoid-shaped bacterial strains KSL-17T, KSL-18 and KSL
      19 were isolated from an alkaline soil in Korea. They were subjected to analysis
      using polyphasic taxonomy. Strains KSL-17T, KSL-18 and KSL-19 grew optimally at
      pH 8.0 and 28 degrees C and in the presence of 0.5 % (w/v) NaCl. They were
      characterized chemotaxonomically as having ll-2,6-diaminopimelic acid in the cell
      wall peptidoglycan, MK-8(H4) as the predominant menaquinone and iso-C(16 : 0) as
      the major fatty acid. Their DNA G+C contents were in the range 74.6-74.8 mol%.
      Strains KSL-17T, KSL-18 and KSL-19 were identical in terms of their 16S rRNA gene
      sequences and exhibited a mean level of DNA-DNA relatedness of 85-90 %.
      Phylogenetic analyses based on 16S rRNA gene sequences showed that strains KSL
      17T, KSL-18 and KSL-19 formed a distinct phylogenetic lineage within the genus
      Nocardioides. The levels of 16S rRNA gene sequence similarity between the three
      strains and the type strains of Nocardioides species were in the range 92.6-95.2
      %. On the basis of phenotypic, genetic and phylogenetic data, strains KSL-17T (=
      KCTC 19039T = DSM 16315T), KSL-18 and KSL-19 should be classified as members of a
      novel species of the genus Nocardioides, for which the name Nocardioides lentus
      sp. nov. is proposed.

PMID- 16403898
TI  - 'Candidatus Phytoplasma fragariae', a novel phytoplasma taxon discovered in
      yellows diseased strawberry, Fragaria x ananassa.
AB  - Symptoms of general stunting and yellowing of leaves were observed in diseased
      cultivated strawberry (Fragaria x ananassa Duchesne) in Lithuania. Analysis of
      16S rRNA gene sequences amplified by PCR indicated that the symptoms were
      associated with infection by a phytoplasma, designated strawberry yellows
      (StrawY) phytoplasma. Phylogenetic analysis of 16S rRNA gene sequences indicated
      that StrawY phytoplasma, 'Candidatus Phytoplasma australiense', 'Candidatus
      Phytoplasma asteris', stolbur phytoplasma and 'Candidatus Phytoplasma japonicum'
      shared a common ancestor, but were mutually distinct. Nucleotide sequence
      alignments of a 1.3 kb 16S rRNA gene sequence fragment revealed that StrawY
      phytoplasma shared 97.4 % or less similarity with previously described
      'Candidatus Phytoplasma' species. These results, in addition to natural host and
      geographical occurrence, support the recognition of StrawY phytoplasma as a
      representative of a novel taxon, 'Candidatus Phytoplasma fragariae'.

PMID- 16403899
TI  - Myceligenerans crystallogenes sp. nov., isolated from Roman catacombs.
AB  - Three xylan-degrading actinobacterial strains were isolated from different
      sampling sites in the Roman catacombs of Domitilla and San Callisto. The
      organisms showed morphological and chemotaxonomic properties such as
      peptidoglycan type A4alpha, L-lys-L-thr-D-Glu; whole-cell sugars (glucose,
      mannose and galactose); octa-, hexa- and tetrahydrogenated menaquinones with nine
      isoprene units; phosphatidylglycerol and diphosphatidylglycerol as the major
      phospholipids; anteiso-C(15 : 0), iso-C(15 : 0) and iso-C(16 : 0) as the
      predominant fatty acids; and a DNA G+C content of 72 mol%. These features are
      consistent with affiliation of these isolates to the genus Myceligenerans. The
      three isolates shared a 16S rRNA gene similarity of 99.9 % and were most closely
      related to Myceligenerans xiligouense DSM 15700T (97.9 % sequence similarity).
      The low level of DNA-DNA relatedness (about 14 %) and the differences in
      phenotypic characteristics between the novel strains and M. xiligouense DSM
      15700T justify the proposal of a novel species of the genus Myceligenerans,
      Myceligenerans crystallogenes sp. nov., with CD12E2-27T (= HKI 0369T = DSM 17134T
      = NCIMB 14061T = VTT E-032285T) as the type strain.

PMID- 16403901
TI  - Rhodotorula pacifica sp. nov., a novel yeast species from sediment collected on
      the deep-sea floor of the north-west Pacific Ocean.
AB  - A novel species of the genus Rhodotorula was isolated from sediments collected on
      the deep-sea floor in the north-west Pacific Ocean. Strains SY-96T, isolated from
      the Yap Trench, and SY-246, isolated from the Iheya Ridge, had almost identical
      nucleotide sequences for their internal transcribed spacers and their 5.8S rDNA.
      Their physiological characteristics were also almost identical. The strains were
      assumed to be related to Rhodotorula mucilaginosa and Rhodotorula dairenensis
      based on sequence similarities in the D1/D2 region of the 26S rDNA. The low DNA
      DNA relatedness and sequence similarity between strain SY-96T and related species
      revealed that strains SY-96T and SY-246 represent a hitherto unknown species. As
      ballistoconidia and sexual reproduction were not observed in strains SY-96T and
      SY-246, these strains are described as Rhodotorula pacifica sp. nov. The type
      strain is SY-96T (= JCM 10908T = CBS 10070T).

PMID- 16403900
TI  - Pseudozyma hubeiensis sp. nov. and Pseudozyma shanxiensis sp. nov., novel
      ustilaginomycetous anamorphic yeast species from plant leaves.
AB  - Among basidiomycetous yeast strains isolated from wilting leaves of various
      plants in China, two groups of Pseudozyma strains were distinguished from the
      others by morphological and physiological characterization. Molecular taxonomic
      analysis based on sequencing of the large subunit (26S) rRNA gene D1/D2 domain
      and internal transcribed spacer (ITS) region confirmed that the two groups
      represent two novel species. They are proposed as Pseudozyma hubeiensis sp. nov.
      (type strain WS 6.4T = AS 2.2493T = CBS 10077T) and Pseudozyma shanxiensis sp.
      nov. (type strain SH 64T = AS 2.2523T = CBS 10075T). The phylogenetic
      relationships of the novel species with described Pseudozyma species and related
      ustilagomycetous teleomorphs were analysed based on the combined sequences of ITS
      and D1/D2. The phenotypic diagnosis of Pseudozyma was emended because of the
      negative inositol assimilation reaction of P. hubeiensis sp. nov., which was
      closely related to the type species of the genus, Pseudozyma prolifica.

PMID- 16403902
TI  - Geotrichum vulgare sp. nov., a novel asexual arthroconidial yeast.
AB  - Two strains of a novel yeast species were isolated from different habitats, from
      soil in an alluvial zone national park in Austria and from a drain in a Turkish
      soft drinks factory. Analysis of the nucleotide sequences of the D1/D2 region of
      their large-subunit rDNAs and PCR fingerprints show that the strains are members
      of the same species, described as Geotrichum vulgare sp. nov. Analysis of
      nucleotide sequences showed that this species is related to the ascogenous genus
      Galactomyces. The closest phylogenetic relative is Geotrichum silvicola, a
      recently described species. The type strain of Geotrichum vulgare is HA1379T (=
      CBS 10073T = NRRL Y-27915T).

PMID- 16403903
TI  - Affiliation of Cochlosoma to trichomonads confirmed by phylogenetic analysis of
      the small-subunit rRNA gene and a new family concept of the order Trichomonadida.
AB  - The protozoan genus Cochlosoma includes parasitic intestinal flagellates of birds
      and mammals of uncertain taxonomic classification. The presence of an adhesive
      disc, superficially similar to that of Giardia, led to a proposal that Cochlosoma
      should be classified as diplomonads. Careful morphological and ultrastructural
      observations, however, revealed conspicuous homologies to trichomonads. We
      addressed the question of classification and phylogenetic affiliation of
      Cochlosoma using the methods of molecular phylogenetics. Analyses based on the
      16S rRNA gene sequence of the species Cochlosoma anatis very robustly placed
      Cochlosoma in the clade of the parabasalid subfamilies Trichomonadinae,
      Trichomitopsiinae and Pentatrichomonoidinae of the order Trichomonadida
      (bootstraps >94 %). The data did not provide robust support for any particular
      position of Cochlosoma within this clade because the sequence suffered from
      mutational saturation and produced a long branch. The most probable sister taxon
      of Cochlosoma is the genus Pentatrichomonas, because their relationship was
      supported specifically by the slowest-mutating, least-saturated positions as
      determined using the method slow-fast. Classification of the order Trichomonadida
      was revised to accommodate knowledge about its phylogeny - the family
      Cochlosomatidae and subfamilies Trichomitopsiinae and Pentatrichomonoidinae were
      abandoned, Trichomonadidae was amended and new families Tritrichomonadidae
      (formerly a subfamily) and Trichomitidae were proposed.

PMID- 16403904
TI  - Candida bracarensis sp. nov., a novel anamorphic yeast species phenotypically
      similar to Candida glabrata.
AB  - Two yeast strains, 153MT and NCYC 3133, isolated from clinical sources in
      separate hospitals were found to be almost identical in the sequences of the
      D1/D2 domain of large-subunit rDNA, the PCR fingerprinting profiles and
      physiological characteristics. The isolates are phenotypically similar, although
      not identical, to Candida glabrata and Kluyveromyces delphensis (recently renamed
      Nakaseomyces delphensis). Sequence analysis of the 26S rDNA D1/D2 gene variable
      region revealed that the two clinical isolates were closely related
      phylogenetically to C. glabrata and K. delphensis, but differed sufficiently to
      justify their assignment as representatives of a separate species. The name
      Candida bracarensis sp. nov. is proposed for the novel species with the type
      strain 153MT (= CBS 10154T = NCYC D3853T = CECT 12000T).

PMID- 16403905
TI  - Clofarabine and cytarabine combination as induction therapy for acute myeloid
      leukemia (AML) in patients 50 years of age or older.
AB  - Outcome of patients with acute myeloid leukemia (AML) who are older than 60 years
      of age remains unsatisfactory, with low remission rates and poor overall
      survival. We have previously established the activity of clofarabine plus
      cytarabine in AML relapse. We have now conducted a phase 2 study of clofarabine
      plus cytarabine in patients aged 50 years or older with previously untreated AML.
      Clofarabine was given at 40 mg/m2 as a 1-hour intravenous infusion for 5 days
      (days 2 to 6) followed 4 hours later by cytarabine at 1 g/m2/d as a 2-hour
      intravenous infusion for 5 days (days 1 to 5). Of 60 patients, 29 (48%) had
      secondary AML, 30 (50%) had abnormal karyotypes (monosomy 5 and/or 7 in 15
      [25%]), and 11 (21%) showed FLT3 abnormalities. The overall response (OR) rate
      was 60% (52% CR, 8% CRp). Four patients (7%) died during induction. Adverse
      events were mainly grade 2 or lower and included diarrhea, nausea, vomiting,
      mucositis, skin reactions, liver test abnormalities, and infusion-related facial
      flushing and headaches. Myelosuppression was common. Clofarabine plus cytarabine
      has activity in adult AML, achieving a good CR rate. However, survival does not
      appear to be improved compared with other regimens. Modifications of this
      combination in AML therapy of older patients warrant further evaluation.

PMID- 16403907
TI  - Growth inhibition and apoptosis in human Philadelphia chromosome-positive
      lymphoblastic leukemia cell lines by treatment with the dual PPARalpha/gamma
      ligand TZD18.
AB  - Treatment of adult Philadelphia chromosome-positive lymphocytic leukemia is
      rarely successful. We report here the effects of TZD18, a novel dual ligand
      specific for peroxisome proliferator-activated receptor alpha and gamma
      (PPARalpha/gamma) on Ph(+) lymphocytic leukemia cell lines BV173, SD1, and SupB
      15. Exposure of these cells to TZD18 resulted in growth inhibition in a dose- and
      time-dependent manner that was associated with G(1) cell cycle arrest. This
      effect was much stronger than that mediated by the PPARgamma ligand pioglitazone
      (PGZ), which also belongs to the thiazolidinediones (TZD) class of ligands.
      However, it may not be mediated through PPARgamma or PPARalpha activation because
      antagonists of PPARgamma and PPARalpha cannot reverse it. Study of the key
      regulators of cell cycle progression by Western blot analysis showed that the
      expression of the cyclin-dependent kinase inhibitor (CDKI) p27(kip1), but not
      that of p21(cip1), was enhanced, whereas that of c-Myc, cyclin E, cyclin D2, and
      cyclin-dependent kinases 2 and 4 (CDK-2 and CDK-4) was decreased when these cells
      were treated with TZD18 (10 or 20 microM). Therefore, the up-regulation of
      p27(kip1) and the down-regulation of CDK-2 and CDK-4 may, at least in part,
      account for the G(1) cell cycle arrest. Furthermore, a remarkable induction of
      apoptosis was observed in the cells treated with this dual ligand. No obvious
      alteration of bcl-2 protein level occurred, but bax was up-regulated in these
      TZD18-treated cells. Activation of caspase 8 and caspase 9 by TZD18 was also
      observed. Importantly, NF-kappaB DNA-binding activity was markedly decreased by
      the TZD18 treatment. In addition, TZD18 enhanced the growth inhibitory effect of
      imatinib, a specific tyrosine kinase inhibitor therapeutically used in the
      treatment of Ph(+) leukemia. Overall, our findings strongly suggest that TZD18
      may offer a new therapeutic approach to aid in the treatment of Ph(+) lymphocytic
      leukemia.

PMID- 16403908
TI  - Bacterial lipopolysaccharide fever is initiated via Toll-like receptor 4 on
      hematopoietic cells.
AB  - Lipopolysaccharide (LPS), a well-known bacterial pyrogen, is recognized by
      several receptors, including the Toll-like receptor 4 (TLR4), on various cells.
      Which of these receptors and cells are linked to fever production is unknown. By
      constructing 4 mouse chimeras and studying their thermoregulatory responses, we
      found that all 3 phases of the typical LPS fever depend on TLR4 signaling. The
      first phase is triggered via the TLR4 on hematopoietic cells. The second and
      third phases involve TLR4 signaling in both hematopoietic and nonhematopoietic
      cells.

PMID- 16403909
TI  - Impact of anemia on hospitalization and mortality in older adults.
AB  - Although anemia is common in older adults, its prognostic significance is
      uncertain. A total of 17 030 community-dwelling subjects 66 years and older were
      identified between July 1 and December 31, 2001, and followed until December 31,
      2004. Cox proportional hazards analyses were performed to determine the
      associations between anemia (defined as hemoglobin < 110 g/L) and hemoglobin and
      all-cause mortality, all-cause hospitalization, and cardiovascular-specific
      hospitalization. Overall, there were 1983 deaths and 7278 first hospitalizations.
      In patients with normal kidney function, adjusting for age, sex, diabetes
      mellitus, and comorbidity, anemia was associated with an increased risk for death
      (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.55-5.12), first all
      cause hospitalization (HR, 2.16; 95% CI, 1.88-2.48), and first cardiovascular
      specific hospitalization (HR, 2.49; 95% CI, 1.99-3.12). An inverse J-shaped
      relationship between hemoglobin and all-cause mortality was observed; the lowest
      risk for mortality occurred at hemoglobin values between 130 to 150 g/L for women
      and 140 to 170 g/L for men. Anemia is associated with an increased risk for
      hospitalization and death in community-dwelling older adults. Consideration
      should be given to redefine "normal" hemoglobin values in the elderly. Clinical
      trials are also necessary to determine whether anemia correction improves quality
      or quantity of life in this population.

PMID- 16403910
TI  - Acceleration of mesoderm development and expansion of hematopoietic progenitors
      in differentiating ES cells by the mouse Mix-like homeodomain transcription
      factor.
AB  - The cellular and molecular events underlying the formation and differentiation of
      mesoderm to derivatives such as blood are critical to our understanding of the
      development and function of many tissues and organ systems. How different
      mesodermal populations are set aside to form specific lineages is not well
      understood. Although previous genetic studies in the mouse embryo have pointed to
      a critical role for the homeobox gene Mix-like (mMix) in gastrulation, its
      function in mesoderm development remains unclear. Hematopoietic defects have been
      identified in differentiating embryonic stem cells in which mMix was genetically
      inactivated. Here we show that conditional induction of mMix in embryonic stem
      cell-derived embryoid bodies results in the early activation of mesodermal
      markers prior to expression of Brachyury/T and acceleration of the mesodermal
      developmental program. Strikingly, increased numbers of mesodermal,
      hemangioblastic, and hematopoietic progenitors form in response to premature
      activation of mMix. Differentiation to primitive (embryonic) and definitive
      (adult type) blood cells proceeds normally and without an apparent bias in the
      representation of different hematopoietic cell fates. Therefore, the mouse Mix
      gene functions early in the recruitment and/or expansion of mesodermal
      progenitors to the hemangioblastic and hematopoietic lineages.

PMID- 16403911
TI  - Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic
      colon cancer: tumor-specific T cells directed to a tumor-associated antigen are
      generated in vivo during GVHD.
AB  - A pilot study was conducted to evaluate safety and activity of nonmyeloablative
      allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC)
      and to determine whether a T-cell response to a tumor-associated antigen (TAA)
      was induced. Fifteen patients with metastatic CRC underwent HCT from human
      leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning
      regimen. All patients engrafted with a median donor T-cell chimerism of 72% at
      day +56. Eight patients experienced grades II to IV acute graft-versus-host
      disease (GVHD). Despite progressive disease before HCT, partial remission and
      disease stabilization longer than 90 days were observed in 1 and 3 patients,
      respectively. Induction of TAA-specific T cells was evaluated with a
      carcinoembryonic antigen (CEA)-specific HLA-A(*)0201 pentamer in 6 patients with
      CRC. CEA-specific CD8(+) T cells were detected in 3 of 3 patients concomitant
      with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not
      detected in 9 of 9 control patients with GVHD who received transplants for
      diagnoses other than CRC. Antitumor activity of CEA-specific T cells was also
      validated in vitro. In one patient, the induction of CEA-specific T cells was
      associated with a decrease of serum CEA levels and a partial response. Thus,
      graft-versus-host reactions associated with allogeneic HCT can trigger the
      generation of T cells specific for CEA, and this may be associated with a
      clinical response.

PMID- 16403912
TI  - Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating
      CD4+ T cells in B-cell non-Hodgkin lymphoma.
AB  - Most non-Hodgkin lymphomas (NHLs) are of B-cell origin, but the tumor tissue can
      be variably infiltrated with T cells. In the present study, we have identified a
      subset of CD4(+)CD25(+) T cells with high levels of CTLA-4 and Foxp3
      (intratumoral T(reg) cells) that are overrepresented in biopsy specimens of B
      cell NHL (median of 17% in lymphoma biopsies, 12% in inflammatory tonsil, and 6%
      in tumor-free lymph nodes; P = .001). We found that these CD4(+)CD25(+) T cells
      suppressed the proliferation and cytokine (IFN-gamma and IL-4) production of
      infiltrating CD4(+)CD25(-) T cells in response to PHA stimulation. PD-1 was found
      to be constitutively and exclusively expressed on a subset of infiltrating
      CD4(+)CD25(-) T cells, and B7-H1 could be induced on intratumoral CD4(+)CD25(+) T
      cells in B-cell NHL. Anti-B7-H1 antibody or PD-1 fusion protein partly restored
      the proliferation of infiltrating CD4(+)CD25(-) T cells when cocultured with
      intratumoral T(reg) cells. Finally, we found that CCL22 secreted by lymphoma B
      cells is involved in the chemotaxis and migration of intratumoral T(reg) cells
      that express CCR4, but not CCR8. Taken together, our results suggest that T(reg)
      cells are highly represented in the area of B-cell NHL and that malignant B cells
      are involved in the recruitment of these cells into the area of lymphoma.

PMID- 16403913
TI  - The angiogenic function of nucleolin is mediated by vascular endothelial growth
      factor and nonmuscle myosin.
AB  - Nucleolin, originally described as a nuclear protein, was recently found to be
      expressed on the surface of endothelial cells during angiogenic. However, the
      functions of cell-surface nucleolin in angiogenic remain mysterious. Here we
      report that upon endothelial cells adhering to extracellular matrix components,
      vascular endothelial growth factor (VEGF) mobilizes nucleolin from nucleus to
      cell surface. Functional blockage or down-regulation of the expression of cell
      surface nucleolin in endothelial cells significantly inhibits the migration of
      endothelial cells and prevents capillary-tubule formation. Moreover, nonmuscle
      myosin heavy chain 9 (MyH9), an actin-based motor protein, is identified as a
      nucleolin-binding protein. Subsequent studies reveal that MyH9 serves as a
      physical linker between nucleolin and cytoskeleton, thus modulating the
      translocation of nucleolin. Knocking down endogenous MyH9, specifically
      inhibiting myosin activity, or overexpressing functional deficient MyH9 disrupts
      the organization of cell-surface nucleolin and inhibits its angiogenic function.
      These studies indicate that VEGF, extracellular matrix, and intracellular motor
      protein MyH9 are all essential for the novel function of nucleolin in angiogenic.

PMID- 16403915
TI  - HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular
      FLICE-inhibitory protein (c-FLIP).
AB  - The HTLV-1 transactivator protein Tax is essential for malignant transformation
      of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL).
      Malignant transformation may involve development of apoptosis resistance. In this
      study we investigated the molecular mechanisms by which HTLV-1 Tax confers
      resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell
      lines derived from HTLV-1-infected patients express elevated levels of c-FLIP(L)
      and c-FLIP(S). The levels of c-FLIP correlated with resistance toward CD95
      mediated apoptosis. Using an inducible system we demonstrated that both
      resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent
      on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family
      member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at
      a CD95 death receptor proximal level in Tax-expressing cells. Finally, using
      siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95
      mediated apoptosis. In conclusion, our data suggest an important mechanism by
      which expression of HTLV-1 Tax may lead to immune escape of infected T cells and,
      thus, to persistent infection and transformation.

PMID- 16403914
TI  - Quantitative PCR on 5 genes reliably identifies CTCL patients with 5% to 99%
      circulating tumor cells with 90% accuracy.
AB  - We previously identified a small number of genes using cDNA arrays that
      accurately diagnosed patients with Sezary Syndrome (SS), the erythrodermic and
      leukemic form of cutaneous T-cell lymphoma (CTCL). We now report the development
      of a quantitative real-time polymerase chain reaction (qRT-PCR) assay that uses
      expression values for just 5 of those genes: STAT4, GATA-3, PLS3, CD1D, and
      TRAIL. qRT-PCR data from peripheral blood mononuclear cells (PBMCs) accurately
      classified 88% of 17 patients with high blood tumor burden and 100% of 12 healthy
      controls in the training set using Fisher linear discriminant analysis (FLDA).
      The same 5 genes were then assayed on 56 new samples from 49 SS patients with
      blood tumor burdens of 5% to 99% and 69 samples from 65 new healthy controls. The
      average accuracy over 1000 resamplings was 90% using FLDA and 88% using support
      vector machine (SVM). We also tested the classifier on 14 samples from patients
      with CTCL with no detectable peripheral involvement and 3 patients with atopic
      dermatitis with severe erythroderma. The accuracy was 100% in identifying these
      samples as non-SS patients. These results are the first to demonstrate that gene
      expression profiling by quantitative PCR on a selected number of critical genes
      can be employed to molecularly diagnosis SS.

PMID- 16403916
TI  - Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia
      (NAIT).
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal incompatibility
      most commonly induced by maternal anti-HPA-1a, IgG alloantibodies against a
      polymorphic epitope of the glycoprotein IIb/IIIa complex in approximately 97.5%
      of white patients. Current guidelines recommend transfusion of immunologically
      compatible platelets to prevent cerebral hemorrhage, the most severe complication
      in affected newborns. Such platelet concentrates, however, are often not readily
      available. In a retrospective analysis in German and Canadian centers, 27
      newborns with NAIT were identified who received platelets from random donors.
      Unexpectedly, 24 of 27 newborns showed an increase above a threshold of 40 x
      10(9) platelets per liter, with moderate (n = 8) or significant (n = 16) platelet
      count increments (more than 80 x 10(9)/L). We conclude that transfusion of
      platelet concentrates from random donors is an appropriate strategy in the
      management of unexpected, severe NAIT predominantly in first pregnancies, pending
      the availability of compatible platelets.

PMID- 16403917
TI  - The cover. New Madrid.

PMID- 16403918
TI  - Genomics proving a powerful tool for mapping the landscape of the brain.

PMID- 16403920
TI  - Groups address reducing newborn deaths.

PMID- 16403919
TI  - Scientists seek cause of drug craving.

PMID- 16403921
TI  - Malaria susceptibility heightened for some.

PMID- 16403922
TI  - Fetal pain.

PMID- 16403923
TI  - Fetal pain.

PMID- 16403924
TI  - Fetal pain.

PMID- 16403925
TI  - Malfunctions of implantable cardioverter defibrillators.

PMID- 16403926
TI  - Heavy night call vs alcohol ingestion in residents.

PMID- 16403927
TI  - Effects of sleep inertia on cognition.

PMID- 16403928
TI  - Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for
      prevention of shocks from implantable cardioverter defibrillators: the OPTIC
      Study: a randomized trial.
AB  - CONTEXT: Implantable cardioverter defibrillator (ICD) therapy is effective but is
      associated with high-voltage shocks that are painful. OBJECTIVE: To determine
      whether amiodarone plus beta-blocker or sotalol are better than beta-blocker
      alone for prevention of ICD shocks. DESIGN, SETTING, AND PATIENTS: A randomized
      controlled trial with blinded adjudication of events of 412 patients from 39
      outpatient ICD clinical centers located in Canada, Germany, United States,
      England, Sweden, and Austria, conducted from January 13, 2001, to September 28,
      2004. Patients were eligible if they had received an ICD within 21 days for
      inducible or spontaneously occurring ventricular tachycardia or fibrillation.
      INTERVENTION: Patients were randomized to treatment for 1 year with amiodarone
      plus beta-blocker, sotalol alone, or beta-blocker alone. MAIN OUTCOME MEASURE:
      Primary outcome was ICD shock for any reason. RESULTS: Shocks occurred in 41
      patients (38.5%) assigned to beta-blocker alone, 26 (24.3%) assigned to sotalol,
      and 12 (10.3%) assigned to amiodarone plus beta-blocker. A reduction in the risk
      of shock was observed with use of either amiodarone plus beta-blocker or sotalol
      vs beta-blocker alone (hazard ratio [HR], 0.44; 95% confidence interval [CI],
      0.28-0.68; P<.001). Amiodarone plus beta-blocker significantly reduced the risk
      of shock compared with beta-blocker alone (HR, 0.27; 95% CI, 0.14-0.52; P<.001)
      and sotalol (HR, 0.43; 95% CI, 0.22-0.85; P = .02). There was a trend for sotalol
      to reduce shocks compared with beta-blocker alone (HR, 0.61; 95% CI, 0.37-1.01; P
      = .055). The rates of study drug discontinuation at 1 year were 18.2% for
      amiodarone, 23.5% for sotalol, and 5.3% for beta-blocker alone. Adverse pulmonary
      and thyroid events and symptomatic bradycardia were more common among patients
      randomized to amiodarone. CONCLUSIONS: Despite use of advanced ICD technology and
      treatment with a beta-blocker, shocks occur commonly in the first year after ICD
      implant. Amiodarone plus beta-blocker is effective for preventing these shocks
      and is more effective than sotalol but has an increased risk of drug-related
      adverse effects.Clinical Trials Registration ClinicalTrials.gov Identifier:
      NCT00257959.

PMID- 16403929
TI  - Effectiveness of managing suspected pulmonary embolism using an algorithm
      combining clinical probability, D-dimer testing, and computed tomography.
AB  - CONTEXT: Previous studies have evaluated the safety of relatively complex
      combinations of clinical decision rules and diagnostic tests in patients with
      suspected pulmonary embolism. OBJECTIVE: To assess the clinical effectiveness of
      a simplified algorithm using a dichotomized clinical decision rule, D-dimer
      testing, and computed tomography (CT) in patients with suspected pulmonary
      embolism. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of consecutive
      patients with clinically suspected acute pulmonary embolism, conducted in 12
      centers in the Netherlands from November 2002 through December 2004. The study
      population of 3306 patients included 82% outpatients and 57% women.
      INTERVENTIONS: Patients were categorized as "pulmonary embolism unlikely" or
      "pulmonary embolism likely" using a dichotomized version of the Wells clinical
      decision rule. Patients classified as unlikely had D-dimer testing, and pulmonary
      embolism was considered excluded if the D-dimer test result was normal. All other
      patients underwent CT, and pulmonary embolism was considered present or excluded
      based on the results. Anticoagulants were withheld from patients classified as
      excluded, and all patients were followed up for 3 months. MAIN OUTCOME MEASURE:
      Symptomatic or fatal venous thromboembolism (VTE) during 3-month follow-up.
      RESULTS: Pulmonary embolism was classified as unlikely in 2206 patients (66.7%).
      The combination of pulmonary embolism unlikely and a normal D-dimer test result
      occurred in 1057 patients (32.0%), of whom 1028 were not treated with
      anticoagulants; subsequent nonfatal VTE occurred in 5 patients (0.5% [95%
      confidence interval {CI}, 0.2%-1.1%]). Computed tomography showed pulmonary
      embolism in 674 patients (20.4%). Computed tomography excluded pulmonary embolism
      in 1505 patients, of whom 1436 patients were not treated with anticoagulants; in
      these patients the 3-month incidence of VTE was 1.3% (95% CI, 0.7%-2.0%).
      Pulmonary embolism was considered a possible cause of death in 7 patients after a
      negative CT scan (0.5% [95% CI, 0.2%-1.0%]). The algorithm was completed and
      allowed a management decision in 97.9% of patients. CONCLUSIONS: A diagnostic
      management strategy using a simple clinical decision rule, D-dimer testing, and
      CT is effective in the evaluation and management of patients with clinically
      suspected pulmonary embolism. Its use is associated with low risk for subsequent
      fatal and nonfatal VTE.

PMID- 16403930
TI  - International prevalence, recognition, and treatment of cardiovascular risk
      factors in outpatients with atherothrombosis.
AB  - CONTEXT: Atherothrombosis is the leading cause of cardiovascular morbidity and
      mortality around the globe. To date, no single international database has
      characterized the atherosclerosis risk factor profile or treatment intensity of
      individuals with atherothrombosis. OBJECTIVE: To determine whether
      atherosclerosis risk factor prevalence and treatment would demonstrate comparable
      patterns in many countries around the world. DESIGN, SETTING, AND PARTICIPANTS:
      The Reduction of Atherothrombosis for Continued Health (REACH) Registry collected
      data on atherosclerosis risk factors and treatment. A total of 67,888 patients
      aged 45 years or older from 5473 physician practices in 44 countries had either
      established arterial disease (coronary artery disease [CAD], n = 40,258;
      cerebrovascular disease, n = 18,843; peripheral arterial disease, n = 8273) or 3
      or more risk factors for atherothrombosis (n = 12,389) between 2003 and 2004.
      MAIN OUTCOME MEASURES: Baseline prevalence of atherosclerosis risk factors,
      medication use, and degree of risk factor control. RESULTS: Atherothrombotic
      patients throughout the world had similar risk factor profiles: a high proportion
      with hypertension (81.8%), hypercholesterolemia (72.4%), and diabetes (44.3%).
      The prevalence of overweight (39.8%), obesity (26.6%), and morbid obesity (3.6%)
      were similar in most geographic locales, but was highest in North America
      (overweight: 37.1%, obese: 36.5%, and morbidly obese: 5.8%; P<.001 vs other
      regions). Patients were generally undertreated with statins (69.4% overall;
      range: 56.4% for cerebrovascular disease to 76.2% for CAD), antiplatelet agents
      (78.6% overall; range: 53.9% for > or =3 risk factors to 85.6% for CAD), and
      other evidence-based risk reduction therapies. Current tobacco use in patients
      with established vascular disease was substantial (14.4%). Undertreated
      hypertension (50.0% with elevated blood pressure at baseline), undiagnosed
      hyperglycemia (4.9%), and impaired fasting glucose (36.5% in those not known to
      be diabetic) were common. Among those with symptomatic atherothrombosis, 15.9%
      had symptomatic polyvascular disease. CONCLUSION: This large, international,
      contemporary database shows that classic cardiovascular risk factors are
      consistent and common but are largely undertreated and undercontrolled in many
      regions of the world.

PMID- 16403931
TI  - Midlife body mass index and hospitalization and mortality in older age.
AB  - CONTEXT: Abundant evidence links overweight and obesity with impaired health.
      However, controversies persist as to whether overweight and obesity have
      additional impact on cardiovascular outcomes independent of their strong
      associations with established coronary risk factors, eg, high blood pressure and
      high cholesterol level. OBJECTIVE: To assess the relation of midlife body mass
      index with morbidity and mortality outcomes in older age among individuals
      without and with other major risk factors at baseline. DESIGN: Chicago Heart
      Association Detection Project in Industry study, a prospective study with
      baseline (1967-1973) cardiovascular risk classified as low risk (blood pressure <
      or =120/< or =80 mm Hg, serum total cholesterol level <200 mg/dL [5.2 mmol/L],
      and not currently smoking); moderate risk (nonsmoking and systolic blood pressure
      121-139 mm Hg, diastolic blood pressure 81-89 mm Hg, and/or total cholesterol
      level 200-239 mg/dL [5.2-6.2 mmol/L]); or having any 1, any 2, or all 3 of the
      following risk factors: blood pressure > or =140/90 mm Hg, total cholesterol
      level > or =240 mg/dL (6.2 mmol/L), and current cigarette smoking. Body mass
      index was classified as normal weight (18.5-24.9), overweight (25.0-29.9), or
      obese (> or =30). Mean follow-up was 32 years. SETTING AND PARTICIPANTS:
      Participants were 17,643 men and women aged 31 through 64 years, recruited from
      Chicago-area companies or organizations and free of coronary heart disease (CHD),
      diabetes, or major electrocardiographic abnormalities at baseline. MAIN OUTCOME
      MEASURES: Hospitalization and mortality from CHD, cardiovascular disease, or
      diabetes, beginning at age 65 years. RESULTS: In multivariable analyses that
      included adjustment for systolic blood pressure and total cholesterol level, the
      odds ratio (95% confidence interval) for CHD death for obese participants
      compared with those of normal weight in the same risk category was 1.43 (0.33
      6.25) for low risk and 2.07 (1.29-3.31) for moderate risk; for CHD
      hospitalization, the corresponding results were 4.25 (1.57-11.5) for low risk and
      2.04 (1.29-3.24) for moderate risk. Results were similar for other risk groups
      and for cardiovascular disease, but stronger for diabetes (eg, low risk: 11.0
      [2.21-54.5] for mortality and 7.84 [3.95-15.6] for hospitalization). CONCLUSION:
      For individuals with no cardiovascular risk factors as well as for those with 1
      or more risk factors, those who are obese in middle age have a higher risk of
      hospitalization and mortality from CHD, cardiovascular disease, and diabetes in
      older age than those who are normal weight.

PMID- 16403932
TI  - Does this patient have deep vein thrombosis?
AB  - CONTEXT: Outpatients with suspected deep vein thrombosis (DVT) have nonspecific
      signs and symptoms. Missed DVT diagnosis may result in fatal pulmonary embolism.
      Since many patients may have DVT, a selective and efficient diagnostic process is
      needed. OBJECTIVE: To systematically review trials that determined the prevalence
      of DVT using clinical prediction rules either with or without D-dimer, for the
      diagnosis of DVT. DATA SOURCES: English- and French-language studies were
      identified from MEDLINE from 1990 to July 2004 and supplemented by a review of
      all relevant bibliographies. STUDY SELECTION: We included studies that
      prospectively enrolled consecutive, unselected outpatients with suspected DVT and
      applied clinical prediction rules before D-dimer testing or diagnostic imaging.
      All studies included sufficient information to allow the calculation of the
      prevalence of DVT for at least 1 of the 3 clinical probability estimates (low,
      moderate, or high). We required that patients be followed up for a minimum 3
      month period. Unless the clinical model incorporated prior DVT, studies were
      excluded if patients with a history of prior DVT were enrolled. DATA EXTRACTION:
      Two reviewers independently reviewed and abstracted data for estimating the
      prevalence of DVT, sensitivity, specificity, and likelihood ratios (LRs) of D
      dimer in each of the 3 clinical probability estimates. Data for the D-dimer in
      all studies were pooled and analyzed as high-sensitivity/low-specificity test or
      a moderate-sensitivity/moderate-specificity test. DATA SYNTHESIS: Fourteen
      studies involving more than 8000 patients used 1 clinical prediction rule for
      diagnosing DVT, of which 11 incorporated D-dimer testing in the diagnostic
      algorithm. The prevalence of DVT in the low, moderate, and high clinical
      probability groups was 5.0% (95% CI, 4.0%-8.0%), 17% (95% CI, 13%-23%), and 53%
      (95% CI, 44%-61%), respectively. The overall prevalence of DVT was 19% (95% CI,
      16%-23%). Pooling all studies, the sensitivity, specificity, and negative LRs of
      D-dimer testing in the low probability group were 88% (95% CI, 81%-92%), 72% (95%
      CI, 65%-78%), and 0.18% (95% CI, 0.12-0.18); in the moderate probability group:
      90% (95% CI, 80%-95%), 58% (95% CI, 49%-67%), and 0.19% (95% CI, 0.11-0.32); and
      in the high probability group: 92% (95% CI, 85%-96%), 45% (95% CI, 37%-52%), and
      0.16% (95% CI, 0.09-0.30). The LRs for a normal result on a high or moderately
      sensitive D-dimer assay among patients with: (1) low clinical suspicion were 0.10
      (95% CI, 0.03-0.37) and 0.20 (95% CI, 0.12-0.31); (2) moderate clinical suspicion
      were 0.05 (95% CI, 0.01-0.21) and 0.23 (95% CI, 0.13-0.39); and (3) high clinical
      suspicion were 0.07 (95% CI, 0.03-0.18) and 0.15 (95% CI, 0.10-0.38).
      CONCLUSIONS: Diagnostic accuracy for DVT improves when clinical probability is
      estimated before diagnostic tests. Patients with low clinical probability on the
      predictive rule have prevalence of DVT of less than 5%. In low-probability
      patients with negative D-dimer results, diagnosis of DVT can be excluded without
      ultrasound; in patients with high clinical suspicion for DVT, results should not
      affect clinical decisions.

PMID- 16403933
TI  - Antiarrhythmic drugs for all patients with an ICD?

PMID- 16403934
TI  - Diagnosing pulmonary embolism with improved certainty and simplicity.

PMID- 16403939
TI  - JAMA patient page. Pulmonary embolism.

PMID- 16403941
TI  - Vascular endothelial growth factor in the lung.
AB  - Vascular endothelial growth factor (VEGF) is a pluripotent growth and
      permeability factor that has a broad impact on endothelial cell function. The
      lung tissue is very rich in this protein; many different lung cells produce VEGF
      and also respond to VEGF. VEGF is critical for the development of the lung and
      serves as a maintenance factor during adult life. In addition to the
      physiological functions of this protein, there is increasing evidence that VEGF
      also plays a role in several acute and chronic lung diseases, such as acute lung
      injury, severe pulmonary hypertension, and emphysema. Here we provide a
      comprehensive overview of the rapidly expanding literature.

PMID- 16403940
TI  - DNA damage and tumor surveillance: one trigger for two pathways.
AB  - Biological evolution ensures that several backup mechanisms always exist to
      prevent the failure of cellular processes of critical importance for life. This
      notion applies to processes aimed at preventing cancer development. Recent
      research suggests that the DNA damage response, activated in one of the earliest
      cellular responses to transformation, may elicit two independent tumor
      surveillance mechanisms. The first, and most well known, is activation of the
      proapoptotic molecule p53 and subsequent cellular suicide. The second, reported
      in a recent study, is induction of the expression of ligands for the activating
      immune receptor NKG2D. That DNA damage induces two independent tumor surveillance
      responses demonstrates how one tumor surveillance mechanism may be assisted by
      another to secure efficient protection against early tumorigenesis. The results
      also support the immunosurveillance theory of cancer and suggest that it may
      operate at very early stages of tumorigenesis.

PMID- 16403942
TI  - Red blood cells increase secretion of matrix metalloproteinases from human lung
      fibroblasts in vitro.
AB  - Tissue remodeling is an important process in many inflammatory and fibrotic lung
      disorders. RBC may in these conditions interact with extracellular matrix (ECM).
      Fibroblasts can produce and secrete matrix components, matrix-degrading enzymes
      (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Imbalance in matrix
      synthesis/degradation may result in rearrangement of tissue architecture and lead
      to diseases such as emphysema or fibrosis. Neutrophil elastase (NE), a protease
      released by neutrophils, is known to activate MMP. We hypothesized that RBC can
      stimulate secretion of MMPs from human lung fibroblasts and that NE can augment
      this effect. Human fetal lung fibroblasts were cultured in floating collagen gels
      with or without RBC. After 4 days, the culture medium was analyzed with gelatin
      zymography, Western blot, and ELISA for MMP-1, -2, -3 and TIMP-1, -2. RBC
      augmented NE-induced fibroblast-mediated collagen gel contraction compared with
      NE alone (18.4+/-1.6%, 23.7+/-1.4% of initial gel area, respectively). A pan-MMP
      inhibitor (GM-6001) completely abolished the stimulating effect of NE. Gelatin
      zymography showed that RBC stimulated MMP-2 activity and that NE enhanced
      conversion to the active form. Addition of GM-6001 completely inhibited MMP-2
      activity in controls, whereas it only partially altered RBC-induced MMP activity.
      Western blot confirmed the presence of MMP-1 and MMP-3 in fibroblasts stimulated
      with RBC, and ELISA confirmed increased concentrations of pro-MMP-1. We conclude
      that stimulation of MMP secretion by fibroblasts may explain the ability of RBC
      to augment fibroblast-mediated collagen gel contraction. This might be a
      potential mechanism by which hemorrhage in inflammatory conditions leads to ECM
      remodeling.

PMID- 16403943
TI  - A novel anti-inflammatory protective action of ethanol ingestion.

PMID- 16403944
TI  - Mechanisms of estrogenic vascular protection.

PMID- 16403945
TI  - Homeostatic functions of vascular endothelial growth factor in adult
      microvasculature.

PMID- 16403946
TI  - Angiotensin-(1-7) prevents development of severe hypertension and end-organ
      damage in spontaneously hypertensive rats treated with L-NAME.
AB  - We examined the influence of chronic treatment with ANG-(1-7) on development of
      hypertension and end-organ damage in spontaneously hypertensive rats (SHR)
      chronically treated with the nitric oxide synthesis inhibitor L-NAME (SHR-L
      NAME). L-NAME administered orally (80 mg/l) for 4 wk significantly elevated mean
      arterial pressure (MAP) compared with SHR controls drinking regular water (269 +/
      10 vs. 196 +/- 6 mmHg). ANG-(1-7) (24 microg x kg(-1) x h(-1)) or captopril (300
      mg/l) significantly attenuated the elevation in MAP due to L-NAME (213 +/- 7 and
      228 +/- 8 mmHg, respectively), and ANG-(1-7) + captopril completely reversed the
      L-NAME-dependent increase in MAP (193 +/- 5 mmHg). L-NAME-induced increases in
      urinary protein were significantly lower in ANG-(1-7)-treated animals (226 +/- 6
      vs. 145 +/- 12 mg/day). Captopril was more effective (96 +/- 12 mg/day), and
      there was no additional effect of captopril + ANG-(1-7) (87 +/- 5 mg/day). The
      abnormal vascular responsiveness to endothelin-1, carbachol, and sodium
      nitroprusside in perfused mesenteric vascular bed of SHR-L-NAME was improved by
      ANG-(1-7) or captopril, with no additive effect of ANG-(1-7) + captopril. In
      isolated perfused hearts, recovery of left ventricular function from 40 min of
      global ischemia was significantly better in ANG-(1-7)- or captopril-treated SHR-L
      NAME, with additive effects of combined treatment. The beneficial effects of ANG
      (1-7) on MAP and cardiac function were inhibited when indomethacin was
      administered with ANG-(1-7), but indomethacin did not reverse the protective
      effects on proteinuria or vascular reactivity. The protective effects of the ANG
      (1-7) analog AVE-0991 were qualitatively comparable to those of ANG-(1-7) but
      were not improved over those of captopril alone. Thus, during reduced nitric
      oxide availability, ANG-(1-7) attenuates development of severe hypertension and
      end-organ damage; prostaglandins participate in the MAP-lowering and
      cardioprotective effects of ANG-(1-7); and additive effects of captopril + ANG-(1
      7) on MAP, but not proteinuria or endothelial function, suggest common, as well
      as different, mechanisms of action for the two treatments. Together, the results
      provide further evidence of a role for ANG-(1-7) in protective effects of
      angiotensin-converting enzyme inhibition and suggest dissociation of factors
      influencing MAP and those influencing end-organ damage.

PMID- 16403947
TI  - Voltage-gated potassium channel Kv1.3 regulates GLUT4 trafficking to the plasma
      membrane via a Ca2+-dependent mechanism.
AB  - Kv1.3 is a voltage-gated K(+) channel expressed in insulin-sensitive tissues. We
      previously showed that gene inactivation or pharmacological inhibition of Kv1.3
      channel activity increased peripheral insulin sensitivity independently of body
      weight by augmenting the amount of GLUT4 at the plasma membrane. In the present
      study, we further examined the effect Kv1.3 on GLUT4 trafficking and tested
      whether it occurred via an insulin-dependent pathway. We found that Kv1.3
      inhibition by margatoxin (MgTX) stimulated glucose uptake in adipose tissue and
      skeletal muscle and that the effect of MgTX on glucose transport was additive to
      that of insulin. Furthermore, whereas the increase in uptake was wortmannin
      insensitive, it was completely inhibited by dantrolene, a blocker of Ca(2+)
      release from intracellular Ca(2+) stores. In white adipocytes in primary culture,
      channel inhibition by Psora-4 increased GLUT4 translocation to the plasma
      membrane. In these cells, GLUT4 protein translocation was unaffected by the
      addition of wortmannin but was significantly inhibited by dantrolene. Channel
      inhibition depolarized the membrane voltage and led to sustained, dantrolene
      sensitive oscillations in intracellular Ca(2+) concentration. These results
      indicate that the apparent increase in insulin sensitivity observed in
      association with inhibition of Kv1.3 channel activity is mediated by an increase
      in GLUT4 protein at the plasma membrane, which occurs largely through a Ca(2+)
      dependent process.

PMID- 16403948
TI  - Anion channels transport ATP into the Golgi lumen.
AB  - Anion channels provide a pathway for Cl(-) influx into the lumen of the Golgi
      cisternae. This influx permits luminal acidification by the organelle's H(+)
      ATPase. Three different experimental approaches, electrophysiological,
      biochemical, and proteomic, demonstrated that two Golgi anion channels, GOLAC-1
      and GOLAC-2, also mediate ATP anion transport into the Golgi lumen. First, GOLAC
      1 and -2 were incorporated into planar lipid bilayers, and single-channel
      recordings were obtained. Low ionic activities of K(2)ATP added to the cis
      chamber directly inhibited the Cl(-) subconductance levels of both channels, with
      K(m) values ranging from 16 to 115 microM. Substitution of either K(2)ATP or
      MgATP for Cl(-) on the cis, trans, or both sides indicated that ATP is conducted
      by the channels with a relative permeability sequence of Cl(-) > ATP(4-) >
      MgATP(2-). Single-channel currents were observed at physiological concentrations
      of Cl(-) and ATP, providing evidence for their importance in vivo. Second,
      transport of [alpha-(32)P]ATP into sealed Golgi vesicles that maintain in situ
      orientation was consistent with movement through the GOLACs because it exhibited
      little temperature dependence and was saturated with an apparent K(m) = 25
      microM. Finally, after transport of [gamma-(32)P]ATP, a protease-protection assay
      demonstrated that proteins are phosphorylated within the Golgi lumen, and after
      SDS-PAGE, the proteins in the phosphorylated bands were identified by mass
      spectrometry. GOLAC conductances, [alpha-(32)P]ATP transport, and protein
      phosphorylation have identical pharmacological profiles. We conclude that the
      GOLACs play dual roles in the Golgi complex, providing pathways for Cl(-) and ATP
      influx into the Golgi lumen.

PMID- 16403949
TI  - Regulation of heavy subunit chain of gamma-glutamylcysteine synthetase by tumor
      necrosis factor-alpha in lens epithelial cells: role of LEDGF/p75.
AB  - TNF-alpha induces oxidative stress by generating reactive oxygen species (ROS).
      This molecule elevates the expression of gamma-glutamylcysteine synthetase heavy
      subunit (gamma-GCS-HS). Lens epithelium-derived growth factor (LEDGF)/p75, a
      transcriptional protein, is inducible by oxidative stress and protects cells from
      various stresses by upregulating stress-responsive genes. This paper presents
      evidence that TNF-alpha elevates the expression of LEDGF and that LEDGF is one of
      the transactivators of gamma-GCS-HS gene. An analysis of the gamma-GCS-HS
      promoter sequence (-819 to +518 nt) revealed the presence of putative sites for
      LEDGF binding. Gel mobility assay confirmed the binding of LEDGF to the heat
      shock element (nGAAn) and the stress response element (A/TGGGGA/T) present in
      gamma-GCS-HS promoter. Transactivation experiments showed activation of gamma-GCS
      HS promoter in cells overexpressing LEDGF or treated with a sublethal dose of TNF
      alpha (20 ng/ml). Downregulation of gamma-GCS-HS promoter activity in cells
      transfected with LEDGF small interfering RNA validated the finding. Notably,
      cells treated with TNF-alpha (20 ng/ml) for 24 h had an increased abundance of
      LEDGF and gamma-GCS-HS mRNA and protein. In contrast, cells treated with TNF
      alpha for longer periods or with higher concentrations of TNF-alpha showed
      reduced expression of LEDGF and gamma-GCS-HS and increased cellular death with
      higher ROS levels. Cells overexpressing LEDGF revealed elevated GSH levels (10
      15%), a condition that may potentially eliminate the insult to cells induced by
      TNF-alpha. Thus TNF-alpha regulation of LEDGF may be physiologically important,
      as elevated expression of LEDGF increases the expression of endogenous gamma-GCS
      HS gene, the catalytic subunit of the regulating enzyme in GSH biosynthesis that
      may constitute a protective mechanism in limiting oxidative stress induced by
      inflammatory cytokines.

PMID- 16403950
TI  - Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve
      muscle function in a mouse model for Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is a frequent muscular disorder caused by mutations
      in the gene encoding dystrophin, a cytoskeletal protein that contributes to the
      stabilization of muscle fiber membrane during muscle activity. Affected
      individuals show progressive muscle wasting that generally causes death by age
      30. In this study, the dystrophic mdx(5Cv) mouse model was used to investigate
      the effects of green tea extract, its major component (-)-epigallocatechin
      gallate, and pentoxifylline on dystrophic muscle quality and function. Three-week
      old mdx(5Cv) mice were fed for either 1 or 5 wk a control chow or a chow
      containing the test substances. Histological examination showed a delay in
      necrosis of the extensor digitorum longus muscle in treated mice. Mechanical
      properties of triceps surae muscles were recorded while the mice were under deep
      anesthesia. Phasic and tetanic tensions of treated mice were increased, reaching
      values close to those of normal mice. The phasic-to-tetanic tension ratio was
      corrected. Finally, muscles from treated mice exhibited 30-50% more residual
      force in a fatigue assay. These results demonstrate that diet supplementation of
      dystrophic mdx(5Cv) mice with green tea extract or (-)-epigallocatechin gallate
      protected muscle against the first massive wave of necrosis and stimulated muscle
      adaptation toward a stronger and more resistant phenotype.

PMID- 16403951
TI  - APOA1-75 G to A substitution associated with severe forms of CAD, lower levels of
      HDL and apoA-I among northern Indians.
AB  - Apolipoprotein A-I (APOA1 gene, apoA-I protein) is the major protein for plasma
      high density lipoprotein (HDL). The relationship of APOA1-75G/A polymorphism with
      lipid profile and coronary artery disease (CAD) is unclear. Out of 370
      individuals initially recruited, 164 angiographically proven CAD patients (>/=
      70% stenosis) and 36 individuals with normal coronaries or insignificant CAD
      (NCAD, </= 50% stenosis) from Delhi and adjoining areas were selected for
      analysis based on the set criteria. Polymorphism was determined by PCR followed
      by MspI restriction digestion. Lipid profile was estimated by enzymatic kit and
      apoA-I levels by immunoturbidimetry. A highly significant increasing trend in 'A'
      allele frequency was observed with the rise in severity of CAD: NCAD (0.097) <
      SVD (single vessel disease) (0.117) < DVD (double vessel disease) (0.223) < TVD
      (triple vessel disease) (0.291). In comparison to GG individuals, the OR of 'A'
      allele carriers to develop SVD, DVD, TVD was 1.3, 2.8 and 4.2 respectively
      (p(trend) = 0.007). Analysis of intergenotypic variations in the lipid profile
      revealed significantly lower levels of HDL and apoA-I among 'A' allele carriers
      as compared to GG (patients). Our study, first of its kind from India, suggests
      that 'A' allele may contribute to severity of CAD and low levels of HDL and apoA
      I. However, an in depth study with a larger set of sample is necessary.

PMID- 16403952
TI  - The Gly482Ser missense mutation of the peroxisome proliferator-activated receptor
      gamma coactivator-1 alpha (PGC-1 alpha) gene associates with reduced insulin
      sensitivity in normal and glucose-intolerant obese subjects.
AB  - Among the putative candidate genes for insulin resistance, the peroxisome
      proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a
      transcriptional coactivator of PPARgamma and alpha, regulating a wide range of
      processes involved in energy production and utilization, such as thermogenesis,
      liver gluconeogenesis, glucose uptake in muscle. In population studies a
      Gly482Ser substitution in PGC-1alpha has been reported to be associated with
      increased risk of type diabetes 2 and insulin resistance. In the present study we
      have analysed the association between the Gly482Ser missense mutation of the PGC
      1alpha gene and insulin sensitivity and glucose tolerance in a population of
      obese non-diabetic subjects. The Gly482Ser SNPs was detected by PCR-RFLP in a
      cohort of 358 Caucasian obese subjects (223 with normal glucose tolerance (NGT)
      and 125 with impaired glucose tolerance (IGT). We observed a significant
      association (p <0.007) between carriers of the Gly482Ser variant of the PGC
      1alpha gene and insulin resistance measured by HOMAIR. Multivariate analysis
      confirmed that the Gly482Ser SNP was a significant (p < 0.02) determinant of
      decreased insulin sensitivity, independently from other well-known modulators of
      insulin action. In conclusion, we have found significant association between the
      Gly482Ser variant of the PGC-1alpha gene and reduced insulin sensitivity in obese
      subjects. This association resulted independent from all other known modulators
      of insulin resistance, and suggests a primary role for the PGC-1alpha gene on the
      genetic susceptibility to insulin resistance in obesity.

PMID- 16403953
TI  - Dietary antioxidants decrease serum soluble adhesion molecule (sVCAM-1, sICAM-1)
      but not chemokine (JE/MCP-1, KC) concentrations, and reduce atherosclerosis in
      C57BL but not apoE*3 Leiden mice fed an atherogenic diet.
AB  - Dietary antioxidants are reported to suppress cellular expression of chemokines
      and adhesion molecules that recruit monocytes to the artery wall during
      atherosclerosis. In the present study we measured the effect of feeding apoE*3
      Leiden mice or their non-transgenic (C57BL) littermates with atherogenic diets
      either deficient in, or supplemented with, dietary antioxidants (vitamin E,
      vitamin C and beta-carotene) for 12 weeks, on serum levels of CC (JE/MCP-1) and
      CXC (KC) chemokines and soluble adhesion molecules (sVCAM-1, sICAM-1) and
      atherosclerotic lesion size. ApoE*3 Leiden mice developed gross
      hypercholesterolaemia, and markedly accelerated (10-20 fold; P < 0.0001)
      atherogenesis, compared with non-transgenic animals. Antioxidant consumption
      reduced lesion area in non-transgenic, but not apoE*3 Leiden, mice. Serum sVCAM-1
      and sICAM-1 levels were significantly (P<0.0001) increased (sVCAM-1 up to 3.9
      fold; sICAM-1 up to 2.4 fold) by 4-8 weeks in all groups, and then declined. The
      initial increase in the concentration of adhesion molecules was reduced by 38%
      61% (P < 0.05) by antioxidant consumption, particularly in non-transgenic mice.
      By contrast, serum chemokine levels tended to increase more rapidly from baseline
      in apoE*3 Leiden mice, compared with non-transgenic animals, but were unaffected
      by dietary antioxidants. We conclude that dietary antioxidants reduce circulating
      soluble adhesion molecules and atherosclerosis in C57BL mice.

PMID- 16403954
TI  - Polymorphisms at the ligand binding site of the vitamin D receptor gene and
      osteomalacia.
AB  - Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible
      determinants of bone mineral density (BMD) and calcium metabolism. In this study,
      our aim was to determine whether there is an association between VDR gene
      polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms
      in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age
      matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were
      also examined. We used PCR and RFLP methods to test for an association between
      osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When
      the control and patients were compared for their ApaI and TaqI genotypes there
      was no relationship between VDR gene allelic polymorphisms and osteomalacia.
      Whereas a nearly significant difference for A allele was found in the allellic
      distribution of the patients (p=0.08). Also no association between biochemical
      data and VDR gene polymorphisms was observed.

PMID- 16403955
TI  - Clinical application of rapid assay of interleukin-6 in influenza-associated
      encephalopathy.
AB  - The characteristics of influenza-associated encephalopathy is the high mortality
      and nimble progress with coma which appears in general cases within 48 hours.
      Most of patients show no abnormalities in the standard blood checks on admission
      or in early stage. In this study we investigated if a rapid assay of interleukin
      (IL)-6 is useful in influenza-associated encephalopathy in early stages. The
      levels of IL-6 in patients with influenza-associated encephalopathy did not show
      any significant difference compared with those in patients with febrile
      convulsion and rotavirus-associated convulsion. However the levels of IL-6 in
      severe cases were significantly higher than those of mild cases with influenza
      associated encephalopathy. Consequently the rapid assay of serum IL-6 is useful
      to evaluate and decide the therapies.

PMID- 16403956
TI  - Daytime of sampling, tooth-brushing and ascorbic acid influence salivary
      thiobarbituric acid reacting substances--a potential clinical marker of gingival
      status.
AB  - BACKGROUND: Salivary thiobarbituric acid reacting substances (TBARS) have been
      previously shown to correlate with the impairment of gingival tissue. Although
      the details on the origin and the composition of this heterogeneous group of
      compounds in saliva are unknown, the potential clinical usefulness makes
      necessary the studies of factors influencing the salivary TBARS levels. AIM: To
      observe the effects of daily dynamics, tooth-brushing and ascorbic acid
      administration on salivary TBARS levels. Subjects and methods. Self-collected
      samples were obtained from 10 young healthy men collecting samples in the
      morning, in the afternoon and in the evening during 2 consecutive days. Ascorbic
      acid (250 mg) was administered orally after the last sampling on day 1 and before
      every sampling on day 2. Additional sampling was performed before and after tooth
      brushing. TBARS levels in saliva specimens were detected spectrofluorometrically.
      Sialic acid content was measured using a modified method of Warren. RESULTS:
      Salivary TBARS levels vary significantly during a day (p < 0.001) with highest
      concentrations in the morning. Both, tooth-brushing (p < 0.05) and short-term
      antioxidative treatment with ascorbic acid (p < 0.005) decrease salivary TBARS
      levels. Sialic acid content of saliva is not influenced significantly by any of
      the investigated factors. CONCLUSION: TBARS levels in saliva are affected by
      daytime of sampling, tooth-brushing and ascorbic acid pre-treatment. These
      results must be considered in clinical research using salivary TBARS levels.
      Sialic acid seems not to be a major component of TBARS in saliva. Further studies
      should clarify the molecular compounds of salivary TBARS and uncover the role of
      oral microbial factors.

PMID- 16403957
TI  - Possible involvement of 4-hydroxynonenal in splenocyte regulated liver
      regeneration.
AB  - Liver regeneration is a complex, systemic process regulated by humoral and
      cellular mechanisms. Inflammatory response to the extensive tissue damage, as in
      partial hepatectomy, plays important role during regeneration. Hence, it is
      assumed that the spleen might play a role in systemic inflammatory response
      involved in liver regeneration. On the other hand, liver damage and consequential
      regeneration are often associated with oxidative stress and lipid peroxidation.
      One of the end products of lipid peroxidation, 4-hydroxynonenal (HNE), is
      nowadays considered not only as a "second toxic messenger of free radicals" but
      also as a growth-regulating factor. We therefore studied in vitro interactions of
      the HNE-treated murine liver cells and autologous spleen cells. The spleen cells
      supported recovery of liver cells from the HNE cytotoxicity although spleen cells
      themselves exerted cytotoxic effects against the proliferating liver cells that
      were not treated with HNE. Our results imply that the cytokines secreted by
      activated immunocompetent cells may be responsible for the observed recovery of
      the HNE-damage liver cells, suggesting that HNE might be an important factor
      regulating cellular and cytokine mediated mechanisms of liver regeneration
      control.

PMID- 16403958
TI  - HNE and Further Lipid Peroxidation Products.

PMID- 16403959
TI  - Total hydroxyoctadecadienoic acid as a marker for lipid peroxidation in vivo.
AB  - An improved method for the measurement of lipid peroxidation in vivo has been
      recently developed, where total hydroxyoctadecadienoic acid (HODE) and 7
      hydroxycholesterol (FCOH) were determined by GC/MS analysis from physiological
      samples after reduction with sodium borohydride and saponification by potassium
      hydroxide. In this method, both free and ester forms of hydroperoxides and
      ketones as well as hydroxides of linoleic acid and cholesterol are measured as
      HODE and FCOH, respectively. The ratio of stereo-isomer, (Z, E)-HODE/(E, E)-HODE,
      could be also measured. In the present study, in order to examine the effect of
      continuous, slow flux of free radicals in vivo, a water-soluble radical generator
      was administered to rats and mice and the amounts of HODE and 8-isoprostane in
      plasma and liver were measured. It was found that the administration of free
      radical-generating azo compound increased the level of HODE and decreased the (Z,
      E)-HODE/(E, E)-HODE ratio in both plasma and liver. The level of HODE was much
      higher than 8-isoprostane.

PMID- 16403960
TI  - Studies of phospholipid oxidation by electrospray mass spectrometry: from
      analysis in cells to biological effects.
AB  - The oxidation of lipids is important in many pathological conditions and lipid
      peroxidation products such as 4-hydroxynonenal (HNE) and other aldehydes are
      commonly measured as biomarkers of oxidative stress. However, it is often useful
      to complement this with analysis of the original oxidized phospholipid.
      Electrospray mass spectrometry (ESMS) provides an informative method for
      detecting oxidative alterations to phospholipids, and has been used to
      investigate oxidative damage to cells, and low-density lipoprotein, as well as
      for the analysis of oxidized phosphatidylcholines present in atherosclerotic
      plaque material. There is increasing evidence that intact oxidized phospholipids
      have biological effects; in particular, oxidation products of 1-palmitoyl-2
      arachidonoyl-sn-glycerophosphocholine (PAPC) have been found to cause
      inflammatory responses, which could be potentially important in the progression
      of atherosclerosis. The effects of chlorohydrin derivatives of lipids have been
      much less studied, but it is clear that free fatty acid chlorohydrins and
      phosphatidylcholine chlorohydrins are toxic to cells at concentrations above 10
      micromolar, a range comparable to that of HNE and oxidized PAPC. There is some
      evidence that chlorohydrins have biological effects that may be relevant to
      atherosclerosis, but further work is needed to elucidate their pro-inflammatory
      properties, and to understand the mechanisms and balance of biological effects
      that could result from oxidation of complex mixtures of lipids in a
      pathophysiological situation.

PMID- 16403961
TI  - Immunohistochemical appearance of HNE-protein conjugates in human astrocytomas.
AB  - Gliomas are tumors originating from astrocytes, oligodendrocytes or ependimal
      cells. Those of astrocytic origin are the most widespread of primary brain tumors
      and account for more then 60% of all CNS neoplasms. The current state of
      knowledge on the associations between tumor etiology and oxidative stress
      suggests that environmental factors that cause oxidative stress could also induce
      and promote cancer, especially in case of hereditary predisposition. Among
      mediators of oxidative stress, lipid peroxidation product 4-hydroxynonenal (HNE)
      is of particular relevance in oncology, as it is known to act as a growth
      regulating factor and a signaling molecule. The aim of present study was to
      investigate by immunohistochemistry the presence of HNE-modified proteins in
      different types of astrocytoma. Our study comprised 45 astrocytic tumors. These
      tumors were graded in accordance with the WHO classification as diffuse
      astrocytomas (DA), anaplastic astrocytomas (AA) and glioblastomas (GB), while
      each group comprised 15 tumors. Slides of paraffin-embedded tumor tissue were
      stained with hematoxylin-eosin or were prepared for immunohistochemistry with
      monoclonal antibodies to HNE-histidine conjugate. Positive immunohistochemical
      reaction to HNE was analyzed semi-quantitatively. HNE positivity was proportional
      with malignancy of astrocytomas. The weakest presence of HNE-histidine adducts
      was found in DA, followed by AA and GB. Lowest intensity of HNE immunopositivity
      was present in tumor cells of almost all DA, predominantly around blood vessels.
      In malignant variants of astrocytoma, AA and GB, HNE positivity was moderate to
      strong, and diffusely distributed in all tumors.

PMID- 16403962
TI  - Do neutrophils produce ozone? An appraisal of current evidence.
AB  - Recently, it was proposed that neutrophils generate ozone. Evidence for the
      proposal is based largely on three experimental systems using probes that are
      known to react with ozone. However, further assessment of the findings shows that
      in each case, there is a plausible alternative explanation. Oxidation of indigo
      carmine to isatin sulfonic can be accounted for by superoxide. Conversion of
      vinylbenzoic acid to p-carboxybenzaldehyde is analogous to the reactions of other
      styrene derivatives shown to be catalyzed by myeloperoxidase, and more rigorous
      assessment of alternative explanations is needed before the formation of
      secosterol oxidation products of cholesterol can be taken as proof of ozone
      production. We conclude that the evidence for ozone production by neutrophils is
      not convincing and studies using the same probes to implicate ozone in other
      biological processes should also be interpreted with caution.

PMID- 16403963
TI  - Myeloperoxidase-induced lipid peroxidation of LDL in the presence of nitrite.
      Protection by cocoa flavanols.
AB  - Lipid peroxidation (LPO) of low-density lipoprotein (LDL) is believed to be a
      pivotal process rendering this plasma lipoprotein atherogenic. Several endogenous
      factors have been proposed to mediate LPO of LDL, among them myeloperoxidase
      (MPO), which is active in atherosclerotic lesions, and the plasma level of which
      has been proposed to be a prognostic parameter for cardiac events. Nitrite, a
      major oxidation product of nitric oxide, is substrate of MPO and a cofactor of
      MPO-mediated LPO under physiological conditions. Dietary flavonoids including (-)
      epicatechin, a major flavan-3-ol in cocoa products, grapes and wine, are
      substrates of MPO as well as potent inhibitors of LPO in LDL at micromolar
      concentrations. Moreover, they strongly suppress protein tyrosine nitration of
      LDL by MPO/nitrite or peroxynitrite. By blunting undesirable MPO-mediated actions
      of nitrite, presumably via scavenging of the strong prooxidant and nitrating *NO2
      radical, dietary flavonoids modulate NO metabolism in a favorable direction and
      thus counteract endothelial dysfunction. This article gives a survey on recent
      progress in this field with special reference to own recently published work.

PMID- 16403964
TI  - A novel test for identifying genes involved in aldehyde detoxification in the
      yeast. Increased sensitivity of superoxide-deficient yeast to aldehydes and their
      metabolic precursors.
AB  - A novel test for the identification of genes involved in aldehyde metabolism is
      proposed, based on detection of altered sensitivity of the yeast to corresponding
      alcohols, metabolic precursors of the aldehydes. This attitude enabled to an
      unexpected detection increased sensitivity of mutants devoid of CuZn-superoxide
      dismutase (CuZnSOD) to allyl alcohol (precursor of acrolein) and nonenol. We
      interpret this finding as due to inactivation of some important element of
      aldehyde detoxification by increased flux of superoxide in DeltaCuZnSOD mutants.

PMID- 16403965
TI  - Interaction of hypohalous acids and heme peroxidases with unsaturated
      phosphatidylcholines.
AB  - The formation of chlorohydrins, bromohydrins, and iodohydrins from 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC) by the myeloperoxidase-hydrogen
      peroxide-halide system was evaluated by means of matrix-assisted laser
      desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. This approach
      allows to detect different kinds of the halogenation reaction even in one mass
      spectrum. Using a mixture of Cl-, Br-, I-, and SCN- at physiological
      concentrations, a bromination of POPC dominates by the MPO-hydrogen peroxide
      halide system. Hypothiocyanite does apparently not react with the double bond of
      POPC, but increasing amounts of SCN- cause a decrease of the bromohydrin peaks.
      An interconversion between different hypohalous acids produced by the
      myeloperoxidase-hydrogen peroxide-halide system determines the pattern of
      halogenohydrins in POPC. Especially, hypochlorous acid is able to oxidise Br- to
      hypobromous acid.

PMID- 16403966
TI  - Carnosine and related dipeptides as quenchers of reactive carbonyl species: from
      structural studies to therapeutic perspectives.
AB  - Carnosine (beta-alanyl-L-histidine) and related peptides such as homocarnosine
      (gamma-amino-butyryl-histidine), balenine beta-alanyl-L-3-methylhistidine) and
      anserine beta-alanyl-L-1-methylhistidine) are histidine-containing dipeptides
      (HD) particularly abundant in excitable tissues such as nervous system and
      skeletal muscle. Although their biochemical role is still unknown, several
      evidences indicate that these endogenous compounds act as quenchers of reactive
      and cytotoxic carbonyl species. In this presentation we will review the
      structural evidences and ex vivo data supporting this hypothesis. We first
      elucidated the reaction mechanism of carnosine as quencher of alpha, beta
      unsaturated aldehydes such as 4-hydroxy-trans-2,3-nonenal (HNE) and acrolein
      (ACR) and then demonstrated the efficacy of carnosine and related peptides as
      detoxifying agents of HNE in spontaneously oxidized rat skeletal muscle, by
      detecting the corresponding HNE-Michael adducts in the crude biological matrix by
      liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI
      MS/MS). Finally, we set-up and validated a sensitive, selective and specific LC
      ESI-MS/MS method for the determination of HD and of the corresponding HNE-Michael
      adducts to monitor their profile in physiological (aging) and pathological
      conditions (diabetes, atherosclerosis) characterized by a carbonyl-mediated
      degenerative overload. The results obtained, beside to give a contribution to the
      understanding of the biochemical role of histidine-dipeptides, provide a strong
      rational to the design of novel derivatives, active as exogenous agents able to
      detoxify carbonyl compounds.

PMID- 16403967
TI  - Dihydroxynonene mercapturic acid, a urinary metabolite of 4-hydroxynonenal, as a
      biomarker of lipid peroxidation.
AB  - The objective of our study was to compare the information obtained through the
      use of three different urinary biomarkers of lipoperoxidation during the time
      course of a bromotrichloromethane (BrCCl3) induced oxidative stress in rats.
      These biomarkers were malondialdehyde (MDA) measured by LC/MS after
      derivatization, the isoprostane 8-iso-PGF2alpha measured by enzyme immunoassay
      and 1,4-dihydroxynonene mercapturic acid (DHN-MA), the major 4-hydroxynonenal
      urinary metabolite [1], measured by LC-MS. Male Wistar rats received a single
      dose of 100 microL/kg BrCCl3 per os and lipid peroxidation was estimated every
      day for a 4-day-period after treatment. MDA, 8-iso-PGF2alpha and DHN-MA
      significantly increased in response to BrCCl3 treatment for this period of time,
      and DHN-MA showed the main increase during the 24-48 h period after treatment.

PMID- 16403968
TI  - Enantioselective metabolism of (R)- and (S)-4-hydroxy-2-nonenal in rat.
AB  - 4-Hydroxy-2-nonenal (HNE) is an endogenous product of lipid peroxidation, which
      is believed to play a biological role in the pathogenesis of various diseases.
      HNE is formed as a racemic mixture of (R)- and (S)- enantiomers. These
      enantiomers differ in their biological properties. The aim of this study was to
      investigate separately the in vivo metabolism of the two HNE enantiomers in male
      rats after intravenous administration of the corresponding radiolabeled compounds
      and to compare the results with those obtained with the racemic mixture. Although
      the difference in the excretion rates was not statistically significant, the HPLC
      profiles of urinary metabolites showed qualitative and quantitative differences
      between the two enantiomers. The level of 3-mercapturic acid-1,4-dihydroxynonane,
      which is considered as the major urinary metabolite of HNE, was significantly
      lower in the case of (S)-HNE injected rats. In vitro studies using rat liver
      cytosolic incubations and HNE-glutathione conjugate as substrate were performed
      to clarify the intermediate pathways involved in their metabolism. Large
      differences were obtained in the reduction and retro-Michael conversion steps of
      the metabolism between the conjugates originating from the two enantiomers.

PMID- 16403969
TI  - Antioxidants prevented oxidative injury of SR induced by Fe2+/H2O2/ascorbate
      system but failed to prevent Ca2+-ATPase activity decrease.
AB  - Dysfunction of sarcoplasmic reticulum (SR) Ca2+-ATPase induced by oxidative
      stress may be a contributing factor to the development of serious age related
      diseases. Incubation of sarcoplasmic reticulum (SR) vesicles of rabbit skeletal
      muscles with Fe2+/H2O2/ascorbate decreased the SH group content of SR
      approximately to 35% and Ca2+-ATPase activity to 50% of control not oxidized
      sample. Protein carbonyls increased twofold, lipid peroxidation was also
      significantly elevated. The antioxidant effects of trolox, the pyridoindole
      derivative stobadine and of the standardized extracts from bark of Pinus Pinaster
      PycnogenolR (Pyc) and from leaves of Ginkgo biloba (EGb 761) were studied on
      oxidatively injured SR. All antioxidants exerted preventive effects against the
      oxidized lipids and protein SH groups of SR vesicles. Trolox and stobadine did
      not influence protein carbonyl formation, while flavonoid extracts prevented
      carbonyl generation, probably by binding to protein. The preventive effects of
      the antioxidants studied on lipids and protein SH groups were however not
      associated with protection of Ca2+-ATPase activity. Stobadine and trolox exerted
      no effect on enzyme activity, Pyc and EGb 761 enhanced the inhibitory effect of
      Ca2+-ATPase activity in oxidatively injured SR. Concluding, under the conditions
      of oxidative stress induced by Fe2+/H2O2/ascorbate against SR of rabbit skeletal
      muscle, the agents studied demonstrated antioxidant effects yet failed to protect
      Ca2+-ATPase activity.

PMID- 16403970
TI  - Oxidative damage to Ca2+-ATPase sarcoplasmic reticulum by HOCl and protective
      effect of some antioxidants.
AB  - Injury of rabbit skeletal sarcoplasmic reticulum (SR) induced by hypochlorous
      acid (HOCl) was studied. HOCl inhibited Ca2+-ATPase activity in a concentration
      dependent manner (IC50=100 micromol/l). The concentration of 13.5 micromol/l HOCl
      reduced the level of sulfhydryl (SH) groups by 50%, yet it did not influence the
      enzyme activity. In comparison with SH group oxidation and enzyme activity
      inhibition, a significantly longer time was necessary for the generation of
      protein carbonyls in SR injured by HOCl. Protective effects of some antioxidants
      (stobadine, trolox, EGb 761, Pycnogenol) were studied in SR oxidatively injured
      by HOCl. Trolox and EGb 761 exerted a protective effect on ATPase activity and on
      SH groups of SR oxidatively modified by HOCl. Stobadine and Pycnogenol inhibited
      markedly protein carbonyl formation. Stobadine was the only antioxidant able to
      scavenge HOCl. In conclusion, the protective effects of antioxidants against
      decrease of Ca2+-ATPase activity induced by HOCl might be caused by protection of
      SH groups. The compounds with both antioxidant and Ca2+-ATPase protecting effect
      offer dual defense against tissue damage occurring, e.g. in aging process.

PMID- 16403971
TI  - Hydroxynonenal and uncoupling proteins: a model for protection against oxidative
      damage.
AB  - In this mini review we summarize recent studies from our laboratory that show the
      involvement of superoxide and the lipid peroxidation product 4-hydroxynonenal in
      the regulation of mitochondrial uncoupling. Superoxide produced during
      mitochondrial respiration is a major cause of the cellular oxidative damage that
      may underlie degenerative diseases and ageing. Superoxide production is very
      sensitive to the magnitude of the mitochondrial protonmotive force, so can be
      strongly decreased by mild uncoupling. Superoxide is able to give rise to other
      reactive oxygen species, which elicit deleterious effects primarily by oxidizing
      intracellular components, including lipids, DNA and proteins. Superoxide-induced
      lipid peroxidation leads to the production of reactive aldehydes, including 4
      hydroxynonenal. These aldehydic lipid peroxidation products are in turn able to
      modify proteins such as mitochondrial uncoupling proteins and the adenine
      nucleotide translocase, converting them into active proton transporters. This
      activation induces mild uncoupling and so diminishes mitochondrial superoxide
      production, hence protecting against disease and oxidative damage at the expense
      of energy production.

PMID- 16403972
TI  - Inhibition of defective adenylosuccinate lyase by HNE: a neurological disease
      that may be affected by oxidative stress.
AB  - Adenylosuccinate lyase is an enzyme of fumarase superfamily that participates in
      the purine biosynthetic pathway, catalysing the nonhydrolytic cleavage of
      succinyl groups from SAICA ribotide and adenylosuccinate. Enzyme defects are
      associated with a human inherited disease, which arises from single point
      mutations to the gene and results in mild to severe psychomotor retardation,
      epilepsy, muscle wasting, and autistic features. Adenylosuccinate lyase activity
      is lost to a different extent in the patients. Diminished levels of enzyme have
      been attributed to loss of catalytic activity, protein instability, or
      environmental factors. P100A/D422Y mutation represents a feasible model for
      studying the effect of cell milieu on the activity of the impaired enzyme. The
      defective enzyme is inhibited by micromolar concentrations of trans-4-hydroxy-2
      nonenal (HNE), a major product of membrane peroxidation that has been found to
      accumulate in brain tissues of patients with neurodegenerative disorders. It is
      suggested that inactivation of defective adenylosuccinate lyase by HNE and other
      membrane peroxidation products may account, at least in part, for the impairment
      of neurological functions and recurrent worsening of the symptoms.

PMID- 16403973
TI  - Inhibition of ion transport ATPases by HNE.
AB  - 4-Hydroxy-2,3-trans-nonenal (HNE), a major lipid peroxidation product, has been
      shown to react with specific amino acid residues of proteins and alter their
      function. In vitro exposure of erythrocyte ghosts and neutrophil membranes to HNE
      results in the inhibition of ion transport ATPases. Neutrophil membrane Ca2+
      ATPase is strongly inhibited by micromolar concentrations of HNE, while HNE is
      considerably less effective against neutrophil Mg2+-ATPase and the erythrocyte
      ghost enzymes.

PMID- 16403974
TI  - The influence of 4-hydroxy-2-nonenal on proliferation, differentiation and
      apoptosis of human osteosarcoma cells.
AB  - The product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE) is known to cause
      cell death at high concentrations, while at lower concentrations it can influence
      cell proliferation and differentiation. In our experiments we used human
      osteosarcoma cells (HOS), to test the influence of HNE on cell proliferation,
      differentiation and induction of apoptosis. Apoptosis induction was estimated by
      TiterTACS TUNEL test. The cells were in parallel counted and the DAPI staining
      method was used to distinguish between apoptotic and necrotic cells as well as to
      define the proportion of cells in mitosis. To test the influence of HNE on HOS
      cell differentiation, cells were treated every second day with HNE. After 10
      days, the cells were stained for alkaline phosphatase, a marker for osteoblast
      differentiation. Cell growth inhibition was caused by supraphysiological
      concentrations of 10 or 100 microM HNE, while apoptosis was induced with
      supraphysiological as well as by the physiological amount of the aldehyde (1
      microM). Necrosis appeared when cells were treated with 10 or 100 microM, but not
      with 1 microM HNE. The proportion of cells in mitosis gradually declined with
      increased HNE concentration. Multiple exposures of HOS cells to 10 microM HNE
      prevented HOS cell differentiation. These results indicated that HNE inhibits
      proliferation and differentiation of HOS cells in the same concentration
      dependent manner as it causes apoptosis. We thus assume that HNE might be one of
      the important signaling molecules regulating the growth of the human osteosarcoma
      cells.

PMID- 16403975
TI  - 4-hydroxynonenal and cell cycle.
AB  - Lipid peroxidation is very low in proliferating cells and tumours and it might
      have a role in the regulation of cell proliferation and differentiation by acting
      through its products. 4-hydroxynonenal (HNE) has been proposed as a mediator of
      lipoperoxidation effects. It has been demonstrated that HNE can inhibit cell
      growth and induce differentiation in different leukemic cell lines. The onset of
      differentiation, induced by HNE, was accompanied by a reduction of c-myc
      expression. In HL-60 cells, HNE induced the accumulation of cells in the G0/G1
      phase of the cell cycle. Cell cycle progression is regulated by three protein
      classes, the cyclins, the cyclin-dependent kinases (CDKs), and the CDK inhibitors
      (CKIs). In HL-60 cells, HNE decreased the expression of cyclin D1, D2 and A and
      caused an increase of p21 (the most important CKI) expression, whereas it did not
      affect CDK expressions. Since cyclins D/CDK2 and cyclin A/CDK2 phosphorylate pRB,
      HNE caused an increase of hypophosphorylated pRb. Hypophosphorylated pRb binds
      and inactivates the E2F transcription factors. Band-shift experiments
      demonstrated that HNE caused a decrease of "free" E2F, as well as an increase of
      pRb (and pRB family members) bound to E2F with consequent repression of the
      transcription.

PMID- 16403976
TI  - Cyto- and genotoxic potential of beta-carotene and cleavage products under
      oxidative stress.
AB  - Free radical attack on beta-carotene results in the formation of high amounts of
      cleavage products with prooxidant activities towards subcellular organelles such
      as mitochondria, a finding which could provide an explanation for the
      contradictory results obtained with beta-carotene in clinical efficacy and cancer
      prevention trials. Since primary hepatocytes proved to be very sensitive
      indicators for the genotoxic action of suspect mutagens/carcinogens we therefore
      investigated a beta-carotene cleavage products mixture (CP), apo-8'-beta
      carotenal (apo-8') and beta-carotene in the primary rat hepatocyte assay in the
      presence and absence of oxidative stress provided by hypoxia/reoxygenation
      (Hy/re). The endpoints tested were: the mitotic indices, the percentages of
      necrotic and apoptotic cells, micronucleated cells (MN), chromosomal aberrations
      (CA) and sister chromatid exchanges (SCE). The results obtained indicate a
      genotoxic potential of both CP and apo-8' already in the concentration range of
      100 nM and 1 microM, i.e. at physiologically relevant levels of beta-carotene and
      beta-carotene breakdown products. In contrast, no significant cytotoxic effects
      of these substances were observed, nor did beta-carotene induce significant
      cytotoxic or genotoxic effects at concentrations ranging from 0.01 up to 10
      microM. However, when beta-carotene is supplemented during oxidative stress
      induced by hypoxia/reoxygenation, a dose-dependent increase of CP is observed
      accompanied by increasing genotoxicity. Furthermore, when beta-carotene cleavage
      products were supplied during oxidative stress significant additional increases
      of genotoxic effects were observed, the additional increases indicating an
      additive effect of both exposures. Summarizing, these results provide strong
      evidence that beta-carotene breakdown products are responsible for the occurrence
      of carcinogenic effects found in the Alpha-Tocopherol Beta-carotene-Cancer
      prevention (ATBC) study and the beta-CArotene and RETinol Efficacy (CARET) Trial.

PMID- 16403977
TI  - Distribution of oxidized and HNE-modified proteins in U87 cells.
AB  - Protein modification is one of the important processes during oxidative stress.
      This modification of proteins is either due to direct oxidation of proteins by
      various oxidants or due to secondary modification by lipid peroxidation products,
      e.g. 4-hydroxynonenal. In the here presented work we compare the intracellular
      distribution of protein modification products after treatment of human U87
      astrocytoma cells with hydrogen peroxide or HNE. The treatment with hydrogen
      peroxide leads mainly to a cytosolic formation of oxidized proteins whereas HNE
      treatment is forming HNE-adducts throughout the cell. Therefore, we concluded
      that HNE diffusion distance in cells enables this lipid peroxidation product to
      act as a second messenger within the cell and on the other hand is the reason for
      the genotoxic properties of this compound.

PMID- 16403978
TI  - Iron regulatory protein 1 as a sensor of reactive oxygen species.
AB  - Iron regulatory proteins (IRP1 and 2) function as translational regulators that
      coordinate the cellular iron metabolism of eukaryotes by binding to the mRNA of
      target genes such as the transferrin receptor or ferritin. In addition to IRP2,
      IRP1 serves as sensor of reactive oxygen species (ROS). As iron and oxygen are
      essential but potentially toxic constituents of most organisms, ROS-mediated
      modulation of IRP1 activity may be an important regulatory element in dissecting
      iron homeostasis and oxidative stress. The responses of IRP1 towards reactive
      oxygen species are compartment-specific and rather complex: H2O2 activates IRP1
      via a signaling cascade that leads to upregulation of the transferrin receptor
      and cellular iron accumulation. Contrary, superoxide inactivates IRP1 by a direct
      chemical attack being limited to the intracellular compartment. In particular,
      activation of IRP1 by H2O2 has established a new regulatory link between
      inflammation and iron metabolism with new clinical implications. This mechanism
      seems to contribute to the anemia of chronic disease and inflammation-mediated
      iron accumulation in tissues. In addition, the cytotoxic side effects of redox
      cycling anticancer drugs such as doxorubicin may involve H2O2-mediated IRP1
      activation. These molecular insights open up new therapeutic strategies for the
      clinical management of chronic inflammation and drug-mediated cardiotoxicity.

PMID- 16403979
TI  - Effect of carotenoid oxidation products on neutrophil viability and function.
AB  - Human neutrophils are short-lived cells that play important roles in host defense
      and acute inflammation by releasing hydrolytic and cytotoxic proteins and
      reactive oxygen derivatives. Apoptosis, a physiological mechanism for cell death,
      regulates both production and survival of neutrophils, representing a basic
      biological mechanism for this type of cells. Carotenoids may react with toxic
      oxygen metabolites released by neutrophils to form a multitude of carotenoid
      cleavage products that exert, in turn, relevant prooxidative biological effects.
      Recent data suggest that carotenoid oxidation products may affect neutrophil
      viability and function by exerting proapoptotic activity and interfering with
      superoxide production by activated cells. The prooxidant and proapoptotic
      activities of carotenoid oxidation products could account, at least in some
      cases, for the procancerogenic properties of carotenoid rich diet.

PMID- 16403980
TI  - Homocysteine induces DNA synthesis and proliferation of vascular smooth muscle
      cells by interfering with MAPK kinase pathway.
AB  - Hyperhomocysteinemia has been identified as an important and independent risk
      factor for cerebral, coronary and peripheral atherosclerosis. However the
      mechanisms by which homocysteine promote atherosclerotic plaque formation are not
      clearly defined. Earlier reports have suggested that homocysteine exert its
      effect via the H2O2 produced during its metabolism. To evaluate which signalling
      molecules are involved in homocysteine induced atherosclerotic changes during the
      pathogenesis of vascular diseases, we examined homocysteine induced smooth muscle
      cell proliferation in the presence of different signal transduction inhibitors.
      We show that MAPK kinase pathway is involved in homocysteine induced DNA
      synthesis and proliferation of vascular smooth muscle cells in the presence of
      the peroxide scavenging enzyme, catalase. Our data suggest that homocysteine
      induces smooth muscle cell growth through a pathway that is independent of H2O2,
      that involves MAPK kinase activation, and that results in accelerated
      atherosclerosis.

PMID- 16403981
TI  - F2-isoprostanes as biomarkers of lipid peroxidation in patients with chronic
      renal failure.
AB  - Chronic renal failure patients on long-term hemolysis are found to be under
      increased oxidative stress, caused by antioxidant deficiency, neutrophil
      activation during hemodialysis (HD), platelet activation and/or chronic
      inflammation. Increased levels of oxidants (e.g. malondialdehyde, 4
      hydroxynonenal, hydrocarbons, lipohydroperoxides, oxycholesterols, carbonyls) in
      HD patients are thought to play an important role in the development of
      endothelial dysfunction, atherogenesis and cardiovascular disease, which is a
      frequent condition in end-stage renal disease. F2-isoprostanes have been
      established as chemically stable, highly specific and reliable biomarkers of in
      vivo oxidative stress which can very sensitively measured by gas chromatography
      mass spectrometry (Morrow et al. [17]). An up to 6-fold increase of plasma F2
      isoprostanes in HD patients is accompanied by an enhanced formation of indicators
      of inflammation (e.g. C-reactive protein) and decreases of endogenous
      antioxidants (e.g. ascorbate, alpha-tocopherol). In their esterified form F2
      isoprostanes may be a useful criteria to evaluate the effectiveness of clinical
      interventions to diminish oxidant stress and associated inflammation.
      Furthermore, F2-isoprostanes possess potent biological activities (e.g. 8-iso
      PGF2alpha is known as a renal vasoconstrictor) suggesting that they may also act
      as mediators of the cellular effects of oxidative stress and inflammation.

PMID- 16403982
TI  - Expression and synthesis of TGFbeta1 is induced in macrophages by 9-oxononanoyl
      cholesterol, a major cholesteryl ester oxidation product.
AB  - Within the broad variety of compounds generated via oxidative reactions in low
      density lipoproteins (LDL) and subsequently found in the atherosclerotic plaque,
      are aldehydes still esterified to the parent lipid and termed core-aldehydes. The
      most represented cholesterol core-aldehyde in LDL is 9-oxononanoyl cholesterol (9
      ONC), an oxidation product of cholesteryl linoleate. Here we report that 9-ONC,
      at concentration actually detectable in biological material, significantly up
      regulates the expression and the synthesis of the pro-fibrogenic cytokine
      transforming growth factor beta1 (TGFbeta1) by cultured macrophages. As
      previously demonstrated for other lipid oxidation products present in LDL, namely
      a biologically representative mixture of oxysterols and the unesterified aldehyde
      4-hydroxynonenal, these effects on TGFbeta1 by 9-ONC further points to LDL lipid
      oxidation as a powerful source of pro-fibrogenic stimuli.

PMID- 16403983
TI  - Role of 4-hydroxy-2,3-nonenal in the pathogenesis of fibrosis.
AB  - Transient activation of fibroblasts or fibroblast-like cells to proliferate and
      to produce elevated quantities of extracellular matrix is essential to fibrosis.
      This activation is regulated by several cytokines produced by various
      inflammation-associated cells. Among these, transforming growth factor beta1
      (TGFbeta1) is considered of major importance. Many studies have shown that lipid
      peroxidation play a key role in the initiation and progression of fibrosis in
      different organs. In fact, 4-hydroxy-2,3-nonenal (HNE), the major aldehydic
      product of lipid peroxidation, is able to induce TGFbeta1 expression and
      synthesis, and activation of activator protein-1 (AP-1) transcription factor. In
      this study, using the murine macrophage line J774-A1, we show that these effects
      are strictly related to the chemical structure of HNE, since neither 2-nonenal
      nor nonanal are biologically active to the same extent. Moreover, we demonstrate
      that HNE can indeed contribute to the onset of fibrosis by stimulating AP-1
      binding to DNA and consequently inducing TGFbeta1 expression, since thiol-group
      reagents, such as N-ethylmaleimide and 4-(chloro-mercuri)-benzenesulfonic acid,
      that down-modulate HNE entrance and localisation inside the cell, prevent both
      phenomena. The possibility to control fibrogenic cytokine levels by means of
      antioxidant or dietetic treatments opens new potential pharmacological and
      nutritional horizons in the treatment of many chronic diseases characterised by
      excessive fibrosis.

PMID- 16403984
TI  - 4-hydroxynonenal and TGF-beta1 concur in inducing antiproliferative effects on
      the CaCo-2 human colon adenocarcinoma cell line.
AB  - 4-Hydroxynonenal (HNE) has been demonstrated to exert its antiproliferative
      effect by up-regulating the c-Jun-N-terminal kinase (JNK), a member of the
      mitogen-activated protein kinase family (MAPKs). Transforming growth factor-beta1
      (TGF-beta1) is the major negative regulatory factor in controlling cell
      proliferation, and Smads are its intracellular transducers. Recent data on human
      colon adenocarcinoma has shown a low HNE content paralleled by a marked
      alteration of TGF-beta1 levels within the tumor mass. The two events appear
      related because of the demonstrated marked ability of HNE to up-regulate
      expression and synthesis of TGF-beta1; the combined decreases of HNE and TGF
      beta1 found in cancer cells provide a favorable condition for neoplastic
      progression. Furthermore, HNE is likely able to interact with the cytokine to
      enhance apoptosis and increase intracellular reactive oxygen species (ROS)
      formation in the CaCo-2 colon carcinoma cell line. The probable mechanism whereby
      HNE and TGF-beta1 interact to induce apoptosis is through cross-talk between the
      main signaling pathways of the two molecules (JNK and Smads), and the observed
      ROS production might only contribute to amplifying the apoptotic pathways. The
      network between the two signaling pathways here involved is now under
      investigation.

PMID- 16403985
TI  - Iron uptake of the normoxic, anoxic and postanoxic microglial cell line RAW
      264.7.
AB  - Iron is one of the trace elements playing a key role in the normal brain
      metabolism. An excess of free iron on the other hand is catalyzing the iron
      mediated oxygen radical production. Such a condition might be a harmful event
      leading perhaps to serious tissue damage and degeneration. Therefore, during
      evolution a complex iron sequestering apparatus developed, minimizing the amount
      of redox-reactive free iron. However, this system might be severely disturbed
      under pathophysiological conditions including hypoxia or anoxia. Since little is
      known about the non-transferrin-mediated iron metabolism of the brain during
      anoxia/reoxygenation, we tested the ability of the microglial cell line RAW 264.7
      to take up iron independently of transferrin under various oxygen concentrations.
      Microglial cells are thought to be the major player in the maintenance of the
      extracellular homeostasis in the brain. Therefore, we investigated the iron
      metabolism of microglial cells employing radiolabeled ferric chloride. We tested
      the uptake of iron under normoxic, anoxic and postanoxic conditions. Furthermore,
      the amount of ferritin was measured by immunoblotting. We were able to show that
      iron enters the microglial cell line in the absence of extracellular transferrin
      under normoxic, anoxic and postanoxic conditions. Interestingly, the amount of
      ferritin is decreasing in the early reoxygenation phase. Therefore, we concluded
      that microglia is able to contribute to the brain iron homeostasis under anoxic
      and postanoxic conditions.

PMID- 16403986
TI  - Copper related toxic effects on cellular protein metabolism in human astrocytes.
AB  - INTRODUCTION: Copper overload due to a defect in the ATPase 7B mediated copper
      excretion within hepatocytes produces the phenotype of Wilson disease. The
      overload of hepatocytes with copper results in necrotic liver cells and is
      accompanied by a high concentration of blood copper levels. That occurs to be the
      reason for increasing neurological copper concentration. Although copper is
      linked to oxidation, there are no data on the direct copper related effects in
      human brain cells. AIM: To test the copper induced changes in protein oxidation
      in human astrocyte like cells. METHODS: We used U87 cells as model for human
      astrocytes. Cells were treated with increasing concentrations of copper(II)
      chloride in Dulbeccos minimal essential medium. Subsequently, at different time
      points we investigated: cellular growth, cellular survival under copper
      treatment, the concentration of oxidized tryptophane in GADPH in vitro as well as
      the carbonyl concentration and the concentration of oxidized proteins in vivo in
      U87 glial cells. RESULTS: The viability of cells decreased with both increasing
      copper concentration and duration of treatment. The concentration of oxidized
      proteins was directly correlated to the increase of copper concentration and
      duration of exposure. CONCLUSION: These observations demonstrate the similarities
      between copper treatment and treatment with other commonly used oxidants,
      including hydrogen peroxide. Furthermore, the vulnerability of astrocytes towards
      copper exposure could be demonstrated. Therefore, these data give further
      insights into understanding of copper metabolism, which in turn is important to
      reveal the exact pathological mechanism in copper related diseases such as Wilson
      disease.

PMID- 16403987
TI  - Effects of vitamin C and aspirin in ischemic stroke-related lipid peroxidation:
      results of the AVASAS (Aspirin Versus Ascorbic acid plus Aspirin in Stroke)
      Study.
AB  - A condition of oxidative stress is known to occur in ischemic stroke, the current
      therapeutic intervention of which is largely limited to thrombolysis. To assess
      the effect of vitamin C - in conjunction to aspirin - in ischemic stroke-related
      lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes
      F2alpha-VI (8,12-iPF2alpha-VI) and activities and levels of a broad spectrum of
      antioxidant enzymes and micronutrients in stroke patients randomized to receive,
      from stroke onset and up to three months, either vitamin C (200 mg/day) plus
      aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week,
      patients treated with vitamin C plus aspirin had higher vitamin C levels (p =
      0.02) and lower 8,12-iPF2alpha-VI levels (p = 0.01) than patients treated with
      aspirin alone. The significance was maintained for the increase of vitamin C
      after three months of therapy (p < 0.01). The clinical functional outcome for
      both groups of patients similarly ameliorated after three months of treatment. We
      conclude that vitamin C, at the dose of 200 mg/day and in conjunction with
      aspirin, significantly decreases ischemic stroke-related lipid peroxidation in
      humans. Further studies are warranted to clarify whether the use of vitamin C may
      add clinical long-term beneficial effects in patients with stroke.

PMID- 16403988
TI  - Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite.
AB  - In vivo measurements in 26 female patients with lipedema and cellulite parameters
      were carried out before and after therapy by means of complex physical
      decongestive therapy (CPDT) including manual lymph drainage and compression as
      main components and/or shock wave therapy (SWT). Oxidative stress parameters of
      blood serum and biomechanic skin properties/smoothening of dermis and hypodermis
      surface were evaluated. Oxidative stress in lipedema and cellulite was
      demonstrated by increased serum concentrations of malondialdehyde (MDA) and
      plasma protein carbonyls compared with healthy control persons. Both MDA and
      protein carbonyls in blood plasma decreased after serial shock wave application
      and CPDT. The SWT itself and CPDT itself lead to MDA release from edematous
      tissue into the plasma. Obviously both therapy types, SWT and CPDT, mitigate
      oxidative stress in lipedema and cellulite. In parallel SWT improved
      significantly the biomechanic skin properties leading to smoothening of dermis
      and hypodermis surface. Significant correlation between MDA depletion of
      edematous and lipid enriched dermis and improvement of mechanic skin properties
      was demonstrated. From these findings it is concluded, that a release of lipid
      peroxidation (LPO) products from edematous dermis is an important sclerosis
      preventing effect of SWT and/or CPDT in lipedema and cellulite. Expression of
      factors stimulating angiogenesis and lymphangiogenesis such as VEGF was not
      induced by SWT and/or CPDT and, therefore, not involved in beneficial effects by
      SWT and/or CPDT.

PMID- 16403989
TI  - Role of 4-hydroxynonenal in the hemozoin-mediated inhibition of differentiation
      of human monocytes to dendritic cells induced by GM-CSF/IL-4.
AB  - In falciparum malaria, rupture of parasitized RBC liberates hemozoin (HZ),
      polymerized heme that contains and generates lipoperoxidation products. In HZ and
      HZ-loaded monocytes 4-HNE attained approx. 50 and 15 microM, respectively. In
      malaria, HZ-loaded monocytes are precursors of dendritic cells (DC). Here, the
      role of 4-HNE as inhibitor of DC differentiation was examined. 4-HNE in HZ was
      quantified after derivatization by HPLC. DC were differentiated in vitro from
      human monocytes supplemented with GM-CSF/IL-4 and analyzed for surface antigens
      and 4-HNE-adducts by FACScan after labelling with specific antibodies. HZ
      loading, or treatment with 4-HNE induced large numbers of 4-HNE-protein-adducts
      on the monocyte membrane. As low as 10 nM 4-HNE inhibited up-regulation of
      functionally important DC differentiation markers. 1 microM 4-HNE elicited
      inhibition of up-regulation of DC differentiation markers as follows: MHC-class I
      and II, -29% and -40%; CD1a, -16%; CD40, -25%; CD54, -27%; and CD83 (the most
      important DC differentiation marker), -45%, with no signs of apoptosis. The
      sequence of additions was important, as the inhibitory effect was reduced when 4
      HNE was added after GM-CSF/IL-4, indicating that GM-CSF/IL-4 receptors could be
      modified by 4-HNE. In conclusion, inhibition of DC differentiation by 4-HNE may
      play a role in malaria immunodepression.

PMID- 16403991
TI  - Pre-operative delivery of a vitamin cocktail diminished oxidative stress after
      vascular surgery in PAD patients - a pilot investigation.

PMID- 16403990
TI  - HNE-dependent molecular damage in diabetic nephropathy and its possible
      prevention by N-acetyl-cysteine and oxerutin.
AB  - Accumulation of Advanced Lipoxidation End-products (ALE), such as MDA- and HNE
      protein adducts, and Advanced Glycation End-products, such as carboxymethyl
      lysine (CML), are probably involved in the development of diabetic nephropathy.
      In this study the effect of some antioxidant treatments (oxerutin, N
      acetylcysteine, taurine and N-acetylcysteine+taurine) on kidney lipoxidative
      damage has been evaluated by immunohistochemistry in streptozotocined rats.
      Diabetic rats showed marked glomerular positivity for ALE, while the samples from
      Control rats were negative. All treatments except taurine were able to protect
      the glomeruli from ALE accumulation; the failure of taurine may be due to
      residual oxidative properties of its derivatives. These data are consistent with
      those of our previous study, which showed that all the antioxidants used except
      taurine protected the glomeruli from diabetes-induced enlargement, increased
      apoptotic rate, decreased cell density and CML accumulation. These data attest to
      a role of glycoxidative and lipoxidative damage in diabetes-dependent damage of
      the kidney, and indicate that specific antioxidants can prevent or attenuate
      diabetic nephropathy.

PMID- 16403992
TI  - Oxidative burst and anticancer activities of rat neutrophils.
AB  - It is assumed that oxidative damage caused by reactive oxygen species (ROS) from
      activated neutrophil granulocytes may contribute to pathology of tumors. ROS are
      crucial in neutrophil-mediated tumor cell lysis. The present study is focused on
      the oxidative burst and antitumorous activities of neutrophils when challenged
      with Walker carcinoma W256. Survival and tumor growth dynamics were monitored in
      vivo, while tumor cell proliferation when mixed with neutrophils was studied in
      vitro together with the generation/release of neutrophil respiratory burst
      products, primarily 1O2. Neutrophils were collected upon Sephadex injection. The
      survival of Sephadex injected animals was slightly improved, while their tumors
      grew less than in controls. The presence of tumor cells in vitro activated
      neutrophils to produce singlet oxygen similar to phorbol ester. Neutrophils from
      Sephadex-bearing animals diminished tumor cell proliferation in vitro (measured
      by 3H-TdR incorporation), while neutrophils from Sephadex and the tumor-bearing
      animals did not show such activity in vitro. Our results confirm that in the case
      of rapidly growing tumors such as murine W256 carcinoma neutrophils have
      antitumorous effects in the early phase of tumor development.

PMID- 16403993
TI  - Effects of lamotrigine on the symptoms and life qualities of patients with post
      polio syndrome: a randomized, controlled study.
AB  - The aim of this study is to find out if lamotrigine gives symptomatic relief and
      enhances quality of life in patients with post-polio syndrome. Thirty patients
      were randomly assigned to receive or not to receive lamotrigine treatment.
      Lamotrigine at a daily dose of 50-100 mg was given to the fifteen patients, and
      fifteen patients were used as the control group. Interventional advice and home
      exercises were given to all of the patients. Clinical assessments were made at
      baseline and repeated at the second and fourth weeks by the physician who was
      unaware of medication. The severity of pain, fatigue and muscle cramps were rated
      on a visual analogue scale. Health-related quality of life was measured using the
      Nottingham Health Profile. The patient's perceived level of fatigue was assessed
      using Fatigue Severity Scale. Comparing to the baseline values, statistically
      significant improvements were obtained in the mean scores of VAS, NHP and FSS at
      two weeks and four weeks in the patients on lamotrigine. No significant
      improvements were reported in the control group. These preliminary results
      indicate that lamotrigine relieves the symptoms and improves the life qualities
      of patients with post polio syndrome.

PMID- 16403994
TI  - The association of sports and physical recreation with life satisfaction in a
      community sample of people with spinal cord injuries.
AB  - The purpose of this study is to assess satisfaction with life domains in people
      with spinal cord injuries (SCI) and investigate whether participation in sports
      and physical recreation is associated with life satisfaction in SCI. 1,748
      randomly selected participants with SCI who fulfilled the criteria: SCI at level
      C5 or below, wheelchair dependent; aged 18-50 at the time of injury; at least 1
      year post-injury, were approached to take part in this study. Completed replies
      were received from 985 individuals with SCI (198 women, 798 men). The measures
      used included the Sports Participation Questionnaire, the Life Satisfaction
      Questionnaire and the Hospital Anxiety and Depression Scale. The numbers of hours
      participating in sports decreased significantly after injury. There was a greater
      decrease in numbers participating in team sports in comparison to the decrease
      seen in numbers participating in individual sports. The highest level of
      satisfaction existed within social domains such as: family life and contacts with
      friends. The lowest level of satisfaction was found in regard to the
      participant's sexual life and vocational situation. Higher satisfaction with life
      in general was demonstrated in respondents with SCI involved in sports or
      physical recreation compared to those not participating in physical activities.

PMID- 16403995
TI  - Pilot study of an energy conservation education program delivered by telephone
      conference call to people with multiple sclerosis.
AB  - OBJECTIVE: To modify and pilot test a face-to-face group energy conservation
      education program for delivery by group telephone teleconference to people with
      multiple sclerosis. PARTICIPANTS: 29 community dwelling individuals with multiple
      sclerosis. METHODS: The first phase of the study involved the modification of an
      existing energy conservation education program to accommodate teleconference
      delivery. The second phase involved a pilot test of the intervention using a
      basic pre/post intervention design. Licensed occupational therapists delivered
      the intervention. OUTCOME MEASURES: Fatigue severity, fatigue impact, health
      related quality of life, self-efficacy for performing energy conservation
      strategies, and use of energy conservation behaviors. FINDINGS: Using an a priori
      alpha of p = 0.10, paired t-tests found significant reductions in fatigue
      severity, fatigue impact, and improvements in the following aspects of quality of
      life: bodily pain and general health. Average effect size was 0.31. The most used
      energy conservation strategies after the course were simplifying activities,
      adjusting priorities, changing body position, resting, and planning the day to
      balance work and rest. CONCLUSION: The pilot study supports on-going development
      and testing of energy conservation education delivered by teleconference to
      people with multiple sclerosis.

PMID- 16403996
TI  - Treatment of agitation following traumatic brain injury: a review of the
      literature.
AB  - Agitation, restlessness, and aggression are frequent neurobehavioural sequelae in
      the early stages of recovery from traumatic brain injury (TBI). These behavioural
      symptoms disrupt patient care and impede rehabilitation efforts. We review the
      current literature (1985 onwards) examining the pharmacological management of
      post-TBI agitation in both acute and post-acute conditions. This article will
      assess the evidence for the use of selected alkylphenols, benzodiazepines,
      estrogens, antiandrogens, neuroleptics/antipsychotics, antidepressants, anti
      Parkinsonian agents, antipsychotics, anticonvulsants, lithium carbonate,
      buspirone, beta-blockers, and psychostimulants in agitated TBI survivors. Review
      of the literature suggests that there is limited evidence to accurately guide
      clinicians in the management of this patient population.

PMID- 16403997
TI  - The effects of loading and unloading treadmill walking on balance, gait, fall
      risk, and daily function in Parkinsonism.
AB  - Our study aims were: 1) to determine whether assisted weight bearing or
      additional weight bearing is more beneficial to the improvement of function and
      increased stability in gait and dynamic balance in patients with Parkinsonism,
      compared with matched controls (treadmill alone). Twenty-three men and women
      participants (M +/- SD = 74.5 +/- 9.7 yrs; Males = 19, Females = 4) with
      Parkinsonism were in the study. Participants staged at 1-7 (M +/- SD = 3.96 +/-
      1.07) using the Hoehn & Yahr scale. All participants were tested before, after
      the intervention (within one week), and four weeks later on: 1) dynamic
      posturography, 2) Berg Balance scale, 3) United Parkinson's Disease Rating Scale
      (UPDRS), 4) biomechanical assessment of strength and range of motion, and 5)
      Gaitrite force sensitive gait mat. Group 1 (treadmill control group), received
      treadmill training with no loading or unloading. Group 2 (unweighted group),
      walked on the treadmill assisted by the Biodex Unweighing System at a 25% body
      weight reduction. Group 3 (weighted group), ambulated wearing a weighted scuba
      diving belt, which increased their normal body weight by 5%. All subjects walked
      on the treadmill for 20 minutes per day for 3 days per week for 6 weeks.
      Improvements in dynamic posturography, falls during balance testing, Berg
      Balance, UPDRS (Motor Exam), and gait for all groups lead us to believe that
      neuromuscular regulation can be facilitated in all Parkinson's individuals no
      matter what treadmill intervention is employed.

PMID- 16403998
TI  - Respiratory muscle strength training: treatment and response duration in a
      patient with early idiopathic Parkinson's disease.
AB  - The outcome of a 20 week expiratory muscle strength training program (EMST) is
      documented in a patient with early idiopathic Parkinson's disease. A pressure
      threshold device was utilized and training occurred in the home setting. The
      training was intensive with a physiologically challenging load specific to the
      expiratory muscles, adjusted weekly based on the participant's performance.
      Results indicated that strength, as indexed by the generation of maximum
      expiratory pressure (MEP), increased by 50% in the first 4 weeks of training,
      consistent with the average strength increase obtained in previous research.
      Strength increases continued beyond the traditional 4 weeks of training with a
      final improvement in MEP of 158% from baseline over the 20 weeks. When the EMST
      was discontinued for a period of 4 weeks, the participant's MEP decreased by 16%
      from the 20 week endpoint measurement. The strength training pattern of the
      expiratory muscles observed in this study was similar to the pattern previously
      reported for limb muscles.

PMID- 16403999
TI  - Pain in Parkinson's disease: pathology to treatment, medication to deep brain
      stimulation.
AB  - This article reviews the current literature on pain in Parkinson's disease to
      include the anatomy, pathology, and both basic and clinical science research. It
      explores treatment methods to include medication management as well as deep brain
      stimulation.

PMID- 16404000
TI  - New aspects for the physiotherapy of pushing behaviour, D. Broetz and H.-O.
      Karnath, Neurorehabilitation 20 (2005), 133-138.

PMID- 16404001
TI  - Physiotherapy for pusher behaviour.

PMID- 16404002
TI  - Centerline-based parametric model of colon for colonoscopy simulator.
AB  - This paper presents a centerline-based parametric model of colon for collision
      detection and visualization of the colon lumen for colonoscopy simulator. The
      prevailing marching cubes algorithm for 3D surface construction can provide a
      high resolution mesh of triangular elements of the colon lumen from CT data. But
      a well organized mesh structure reflecting the geometric information of the colon
      is essential to fast and accurate computation of contact between the colonoscope
      and colon, and the corresponding reflective force in the colonoscopy simulator.
      The colon is modeled as parametric arrangement of triangular elements with its
      surface along the centerline of the colon. All the vertices are parameterized
      according to the radial angle along the centerline, so that the triangles around
      the viewpoint can be found fast. The centerline-based parametric colon model has
      75,744 triangular elements compared to 373,364 of the model constructed by the
      marching cubes algorithm.

PMID- 16404003
TI  - New tools for sculpting cranial implants in a shared haptic augmented reality
      environment.
AB  - New volumetric tools were developed for the design and fabrication of high
      quality cranial implants from patient CT data. These virtual tools replace time
      consuming physical sculpting, mold making and casting steps. The implant is
      designed by medical professionals in tele-immersive collaboration. Virtual clay
      is added in the virtual defect area on the CT data using the adding tool. With
      force feedback the modeler can feel the edge of the defect and fill only the
      space where no bone is present. A carving tool and a smoothing tool are then used
      to sculpt and refine the implant. To make a physical evaluation, the skull with
      simulated defect and the implant are fabricated via stereolithography to allow
      neurosurgeons to evaluate the quality of the implant. Initial tests demonstrate a
      very high quality fit. These new haptic volumetric sculpting tools are a critical
      component of a comprehensive tele-immersive system.

PMID- 16404004
TI  - Reification of abstract concepts to improve comprehension using interactive
      virtual environments and a knowledge-based design: a renal physiology model.
AB  - Several abstract concepts in medical education are difficult to teach and
      comprehend. In order to address this challenge, we have been applying the
      approach of reification of abstract concepts using interactive virtual
      environments and a knowledge-based design. Reification is the process of making
      abstract concepts and events, beyond the realm of direct human experience,
      concrete and accessible to teachers and learners. Entering virtual worlds and
      simulations not otherwise easily accessible provides an opportunity to create,
      study, and evaluate the emergence of knowledge and comprehension from the direct
      interaction of learners with otherwise complex abstract ideas and principles by
      bringing them to life. Using a knowledge-based design process and appropriate
      subject matter experts, knowledge structure methods are applied in order to
      prioritize, characterize important relationships, and create a concept map that
      can be integrated into the reified models that are subsequently developed.
      Applying these principles, our interdisciplinary team has been developing a
      reified model of the nephron into which important physiologic functions can be
      integrated and rendered into a three dimensional virtual environment called
      Flatland, a virtual environments development software tool, within which a
      learners can interact using off-the-shelf hardware. The nephron model can be
      driven dynamically by a rules-based artificial intelligence engine, applying the
      rules and concepts developed in conjunction with the subject matter experts. In
      the future, the nephron model can be used to interactively demonstrate a number
      of physiologic principles or a variety of pathological processes that may be
      difficult to teach and understand. In addition, this approach to reification can
      be applied to a host of other physiologic and pathological concepts in other
      systems. These methods will require further evaluation to determine their impact
      and role in learning.

PMID- 16404005
TI  - A surgical and fine-motor skills trainer for everyone? Touch and force-feedback
      in a virtual reality environment for surgical training.
AB  - Access to the laboratory component of a class is limited by resources, while lab
      training is not currently possible for distance learning. To overcome the problem
      a solution is proposed to enable hands-on, interactive, objectively scored and
      appropriately mentored learning in a widely accessible environment. The proposed
      solution is the Virtual-Reality Motor-Skills trainer to teach basic fine-motor
      skills using Haptics for touch and feel interaction as well as a 3D virtual
      reality environment for visualization.

PMID- 16404006
TI  - A topologically faithful, tissue-guided, spatially varying meshing strategy for
      the computation of patient-specific head models for endoscopic pituitary surgery
      simulation.
AB  - This paper presents a method for tessellating tissue boundaries and their
      interiors, given as input a tissue map consisting of relevant classes of the
      head, in order to produce anatomical models for finite element-based simulation
      of endoscopic pituitary surgery. Our surface meshing method is based on the
      simplex model, which is initialized by duality from the topologically accurate
      results of the Marching Cubes algorithm, and which features explicit control over
      mesh scale, while using tissue information to adhere to relevant boundaries. Our
      mesh scale strategy is spatially varying, based on the distance to a central
      point or linearized surgical path. The tetrahedralization stage also features a
      spatially varying mesh scale, consistent with that of the surface mesh.

PMID- 16404007
TI  - Determination of face validity for the Simbionix LAP mentor virtual reality
      training module.
AB  - This study determines the expert and referent face validity of LAP Mentor, the
      first procedural virtual-reality (VR) trainer. After a hands-on introduction to
      the simulator a questionnaire was administered to 49 participants (21 expert
      laparoscopists and 28 novices). There was a consensus on LAP Mentor being a valid
      training model for basic skills training and the procedural training of
      laparoscopic cholecystectomies. As 88% of respondents saw training on this
      simulator as effective and 96% experienced this training as fun it will likely be
      accepted in the surgical curriculum by both experts and trainees. Further
      validation of the system is required to determine whether its performance concurs
      with these favourable expectations.

PMID- 16404009
TI  - The Surgical Simulation and Training Markup Language (SSTML): an XML-based
      language for medical simulation.
AB  - Under contract with the Telemedicine & Advanced Technology Research Center
      (TATRC), Energid Technologies is developing a new XML-based language for
      describing surgical training exercises, the Surgical Simulation and Training
      Markup Language (SSTML). SSTML must represent everything from organ models
      (including tissue properties) to surgical procedures. SSTML is an open language
      (i.e., freely downloadable) that defines surgical training data through an XML
      schema. This article focuses on the data representation of the surgical
      procedures and organ modeling, as they highlight the need for a standard language
      and illustrate the features of SSTML. Integration of SSTML with software is also
      discussed.

PMID- 16404008
TI  - Enhancing the visual realism of hysteroscopy simulation.
AB  - Visualization is a very important part of a high fidelity surgical simulator. Due
      to modern computer graphics hardware, which offers more and more features and
      processing power, it is possible to extend the standard OpenGL rendering methods
      with advanced visualization techniques to achieve highly realistic rendering in
      real-time. For an easy and efficient use of these new capabilities, a stand-alone
      graphics engine has been implemented, which exploits these advanced rendering
      techniques and provides an interface in order to ensure the interoperability with
      a software framework for surgical simulators.

PMID- 16404010
TI  - Online robust model estimation during in vivo needle insertions.
AB  - Soft tissue modeling is of key importance in medical robotics and simulation. In
      the case of percutaneous operations, a fine model of layers transitions and
      target tissues is required. However, the nature and the variety of these tissues
      is such that this problem is extremely complex. In this article, we propose a
      method to estimate the interaction between in vivo tissues and a surgical needle.
      The online robust estimation of a varying parameters model is achieved during an
      insertion in standard operating conditions.

PMID- 16404012
TI  - Augmented assessment as a means to augmented reality.
AB  - Rigorous scientific assessment of educational technologies typically lags behind
      the availability of the technologies by years because of the lack of validated
      instruments and benchmarks. Even when the appropriate assessment instruments are
      available, they may not be applied because of time and monetary constraints. Work
      in augmented reality, instrumented mannequins, serious gaming, and similar
      promising educational technologies that haven't undergone timely, rigorous
      evaluation, highlights the need for assessment methodologies that address the
      limitations of traditional approaches. The most promising augmented assessment
      solutions incorporate elements of rapid prototyping used in the software
      industry, simulation-based assessment techniques modeled after methods used in
      bioinformatics, and object-oriented analysis methods borrowed from object
      oriented programming.

PMID- 16404011
TI  - A software framework for surgical simulation virtual environments.
AB  - Surgical simulators are an integration of many models, capabilities, and
      functions. Development of a working simulator requires the flexibility to
      integrate various software models, to support interoperability, and facilitate
      performance optimizations. An object oriented framework is devised to support
      multithreaded integration of simulation, deformation, and interaction. A
      demonstration application has been implemented in Java, leveraging the features
      that are built into the language including multithreading, synchronization, and
      serialization. Future work includes expanding the capabilities of the framework
      with a broader range of model and interactive capabilities.

PMID- 16404013
TI  - A holographic collaborative medical visualization system.
AB  - We report on our work on the development of a novel holographic display
      technology, capable of targeting multiple freely moving naked eye viewers, and of
      a demonstrator, exploiting this technology to provide medical specialists with a
      truly interactive collaborative 3D environment for diagnostic discussions and/or
      pre-operative planning.

PMID- 16404014
TI  - Bounds for damping that guarantee stability in mass-spring systems.
AB  - Mass-spring systems are often used to model anatomical structures in medical
      simulation. They can produce plausible deformations in soft tissue, and are
      computationally efficient. Determining damping values for a stable mass-spring
      system can be difficult. Previously stable models can become unstable with
      topology changes, such as during cutting. In this paper, we derive bounds for the
      damping coefficient in a mass-spring system. Our formulation can be used to
      evaluate the stability for user specified damping values, or to compute values
      that are unconditionally stable.

PMID- 16404015
TI  - Bootstrapped ultrasound calibration.
AB  - This paper introduces an enhanced (bootstrapped) method for tracked ultrasound
      probe calibration. Prior to calibration, a position sensor is used to track an
      ultrasound probe in 3D space, while the US image is used to determine calibration
      target locations within the image. From this information, an estimate of the
      transformation matrix of the scan plane with respect to the position sensor is
      computed. While all prior calibration methods terminate at this phase, we use
      this initial calibration estimate to bootstrap an additional optimization of the
      transformation matrix on independent data to yield the minimum reconstruction
      error on calibration targets. The bootstrapped workflow makes use of a closed
      form calibration solver and associated sensitivity analysis, allowing for rapid
      and robust convergence to an optimal calibration matrix. Bootstrapping
      demonstrates superior reconstruction accuracy.

PMID- 16404016
TI  - Combining high-fidelity human patient simulators with a standardized family
      member: a novel approach to teaching breaking bad news.
AB  - Our novel approach to teaching Breaking Bad News (BBN) involves having students
      actively participate in an unsuccessful resuscitation (mannequin) followed
      immediately by BBN to a standardized patient wife (SPW) portrayed by an actress.
      Thirty-nine 3(rd) year medical students completed a questionnaire and then were
      divided as follows: Group 1 (n=21) received little to no training prior to
      speaking with the SPW. Group 2 (n =18) received a lecture and practiced for 1
      hour in small groups prior to the resuscitation and BBN. Both groups self
      assessed ability to BBN (p<.0002 & p<.00001), and ability to have a plan (p<.0004
      & p <.0003) improved significantly over base line with greater improvement in
      group 2. Group 2 (pre-trained) students were rated superior by SPW's in several
      key areas. This novel approach to teaching BBN to 3(rd) year medical students was
      well received by the students and resulted in marked improvement of self assessed
      skills over baseline.

PMID- 16404017
TI  - Virtual environment-based training simulator for endoscopic third
      ventriculostomy.
AB  - A virtual environment-based endoscopic third ventriculostomy simulator is being
      developed for training neurosurgeons as a standardized method for evaluating
      competency. Magnetic resonance (MR) images of a patient's brain are used to
      construct the geometry model, realistic behavior in the surgical area is
      simulated by using physical modeling and surgical instrument handling is
      replicate by a haptic interface. The completion of the proposed virtual training
      simulator will help the surgeon to practice the techniques repeatedly and
      effectively, serving as a powerful educational tool.

PMID- 16404018
TI  - Evaluation methods of a middleware for networked surgical simulations.
AB  - Distributed surgical virtual environments are desirable since they substantially
      extend the accessibility of computational resources by network communication.
      However, network conditions critically affects the quality of a networked
      surgical simulation in terms of bandwidth limit, delays, and packet losses, etc.
      A solution to this problem is to introduce a middleware between the simulation
      application and the network so that it can take actions to enhance the user
      perceived simulation performance. To comprehensively assess the effectiveness of
      such a middleware, we propose several evaluation methods in this paper, i.e.,
      semi-automatic evaluation, middleware overhead measurement, and usability test.

PMID- 16404019
TI  - A biomechanical analysis of surgeon's gesture in a laparoscopic virtual scenario.
AB  - Minimally invasive surgery (MIS) has become very common in recent years thanks to
      many advantages that patients can get. However, due to the difficulties surgeons
      encounter to learn and manage this technique, several training methods and
      metrics have been proposed in order to, respectively, improve surgeon's abilities
      and assess his/her surgical skills. In this context, this paper presents a
      biomechanical analysis method of the surgeon's movements, during exercise
      involving instrument tip positioning and depth perception in a laparoscopic
      virtual environment. Estimation of some biomechanical parameters enables us to
      assess the abilities of surgeons and to distinguish an expert surgeon from a
      novice. A segmentation algorithm has been defined to deeply investigate the
      surgeon's movements and to divide them into many sub-movements.

PMID- 16404020
TI  - Smart tool for force measurements during knee arthroscopy: in vivo human study.
AB  - This paper describes the magnitude and patterns of forces obtained by using a
      probe, equipped with a six-axis force torque sensor, in knee arthroscopy. The
      probe was used by orthopaedic surgeons and trainees, who performed 11 different
      tasks in 10 standard knee arthroscopies. The force magnitude and patterns
      generated are presented; which can support the development of virtual arthroscopy
      systems with realistic haptic feedback. The results were compared across both
      groups of surgeons. A difference in the force patterns generated by senior versus
      junior surgeons was noted which can aid in the development of an objective
      assessment system for arthroscopy skills. The results could potentially be useful
      to assess future performance in real arthroscopy.

PMID- 16404021
TI  - Factors affecting targeting using the computer assisted orthopaedic surgery
      system (CAOSS).
AB  - An advantage of CAOS over traditional surgery is improved precision of implant
      position and trajectories in 3D space. However, the implementation of these
      trajectories often adds an extra step to the operation that increases operative
      time and requires extra training. This paper reports a study of variation in time
      to-task and learning curve in performing a standard task of targeting in 3D space
      using Hull's CAOSS. It shows that time-to-task can be reduced by replacing a 3D
      targeting task with multiple independent 2D targeting tasks whilst potentially
      reducing targeting error. Based on this better understanding of targeting a novel
      jig was developed for performing dynamic hip Screw (DHS) insertion using CAOSS
      that would provide improved targeting performance by the surgeon.

PMID- 16404022
TI  - Contouring in 2D while viewing stereoscopic 3D volumes.
AB  - The ability to manually specify contours in a volumetric data is often required
      in situations when automatic algorithms are unable to accurately extract the
      desire volume. Conventionally, the contours are drawn over a slice, working on
      plane-by-plane basis usually constrained to orthogonal planes. In defining the
      contour on a 2D image, the user faces the problem of loosing 3D context (does the
      tissue belong to inside the contour or outside?). This requires the constant back
      and forth movement from a plane view where the interaction takes place (usually
      with the mouse) to the 3D volumetric view that provides the contextual
      information. We present an interactive environment that allows for efficient
      contouring while providing contextual 3D information to the user.

PMID- 16404023
TI  - Integrative haptic and visual interaction for simulation of PMMA injection during
      vertebroplasty.
AB  - In vertebroplasty, physician relies on both sight and feel to properly place the
      bone needle through various tissue types and densities, and to help monitor the
      injection of PMMA or cement into the vertebra. Incorrect injecting and reflux of
      the PMMA into areas where it should not go can result in detrimental clinical
      complication. This paper focuses on the human-computer interaction for simulating
      PMMA injection in our virtual spine workstation. Fluoroscopic images are
      generated from the CT patient volume data and simulated volumetric flow using a
      time varying 4D volume rendering algorithm. The user's finger movement is
      captured by a data glove. Immersion CyberGrasp is used to provide the variable
      resistance felt during injection by constraining the user's thumb. Based on our
      preliminary experiments with our interfacing system comprising simulated
      fluoroscopic imaging and haptic interaction, we found that the former has a
      larger impact on the user's control during injection.

PMID- 16404024
TI  - Flow visualization for interactive simulation of drugs injection during
      chemoembolization.
AB  - Chemoembolization is an important therapeutic procedure. A catheter was navigated
      to the artery that feeds the tumor, and chemotherapy drugs and embolus are
      injected directly into the tumor. There is a risk that embolus may lodge
      incorrectly and deprive normal tissue of its blood supply. This paper focuses on
      visualization of the flow particles in simulation of chemotherapy drugs injection
      for training of hand-eye coordination skills. We assume that the flow follows a
      defined path in the hepatic vascular system from the catheter tip. The vascular
      model is constructed using sweeping and blending operations. Quadrilaterals which
      are aligned to face the viewer are drawn for the trail of each particle. The
      quadrilateral in the trail is determined using bilinear interpolation. On
      simulated fluoroscopic image, the flow is rendered as overlaying and
      semitransparent quadrilaterals representing the particles' trails. This
      visualization model achieves a good visual approximation of the flow of particles
      inside the vessels under fluoroscopic imaging.

PMID- 16404025
TI  - The use of a Computer Aided Design (CAD) environment in 3D reconstruction of
      anatomic surfaces.
AB  - Paper presents an evaluation and comparison of two different types of software
      for generating a 3D model from medical imaging data: first, a dedicated 3D
      reconstruction Mimics interface, by Materialise and second, an engineering CAD (a
      Solid Works and AutoCAD) interface. Advantages and limitations of both software
      types are outlined and there some observations for 3D reconstruction of anatomic
      surfaces are presented.

PMID- 16404026
TI  - Simulating the domain of medical modeling and simulation: the medical modeling
      and simulation database.
AB  - Over the past year the National Center for Collaboration in Medical Modeling and
      Simulation's (NCCMMS) Medical Modeling and Simulation Database (MMSD) has grown
      dramatically. There are now over 170,000 entries including current articles and
      upcoming conference listings. In addition, in the near future, the scope of the
      NCCMMS website will expand to include an evaluation section where NCCMMS
      researchers will compile data describing the efficacy and cost efficiency of many
      commercially available simulators. The NCCMMS also plans to create a new
      collaborative forum on the website. This message board area will provide a single
      location for researchers to discuss new simulation techniques and programs. It
      will help to facilitate communication between companies and researchers in the
      field by creating a comprehensive forum for medical modeling and simulation
      discussions. The newly expanded MMSD and NCCMMS websites are designed to create a
      simple way for researchers and companies to work together to facilitate the
      sharing of information and to spur advancement of the medical modeling and
      simulation discipline.

PMID- 16404027
TI  - Assessing cognitive & motor performance in minimally invasive surgery (MIS) for
      training & tool design.
AB  - The objective of this paper is to present the development of a new modelling
      diagram (MCMD) to represent MIS procedures in terms of both motor and cognitive
      actions. Through observation and analysis of several laparoscopic cholecystectomy
      procedures and based on task analysis techniques, we created a diagram language
      composed of six primary symbols: processes, decisions, interrupt service routines
      (ISRs), options points and AND and OR gates. We then tested and refined them
      during 10 new cases until no further changes seemed necessary, we have since
      applied this approach to 6 laparoscopic colorectal surgeries and have found that
      no further symbols were necessary though the procedural representation was
      naturally different. This modelling diagram allowed us to represent both
      cognitive and motor performance aspects of surgical procedures in a unified
      framework and will in future allow us to assess motor performance on particular
      surgical tasks at particular points in the procedure (i.e., the surgical
      context).

PMID- 16404028
TI  - Virtual patients: assessment of synthesized versus recorded speech.
AB  - Virtual patients have great potential for training patient-doctor communication
      skills. There are two approaches to producing the virtual human speech:
      synthesized speech or recorded speech. The tradeoffs in flexibility, fidelity,
      and cost raise an interesting development decision: which speech approach is most
      appropriate for virtual patients? Two groups of medical students participated in
      a user study interviewing a virtual patient under each condition. We found no
      significant differences in the overall impression, speech intelligibility, and
      task performance. Our conclusion is that if the goal is to train students of
      which questions to ask, synthesized speech is just as effective as recorded
      speech. However, if the goal is to teach the student how to ask the correct
      questions, a high level of expressiveness in the virtual patient is needed. This
      in turn necessitates the higher cost - even with the lower flexibility - of
      recorded speech.

PMID- 16404029
TI  - Needle artifact localization in 3T MR images.
AB  - This work explores an image-based approach for localizing needles during MRI
      guided interventions, for the purpose of tracking and navigation. Susceptibility
      artifacts for several needles of varying thickness were imaged, in phantoms,
      using a 3 tesla MRI system, under a variety of conditions. The relationship
      between the true needle positions and the locations of artifacts within the
      images, determined both by manual and automatic segmentation methods, have been
      quantified and are presented here.

PMID- 16404030
TI  - Robot-assisted needle placement in open-MRI: system architecture, integration and
      validation.
AB  - This work describes an integrated system for planning and performing percutaneous
      procedures-such as prostate biopsy-with robotic assistance under MRI-guidance.
      The physician interacts with a planning interface in order to specify the set of
      desired needle trajectories, based on anatomical structures and lesions observed
      in the patient's MR images. All image-space coordinates are automatically
      computed, and used to position a needle guide by means of an MRI-compatible
      robotic manipulator, thus avoiding the limitations of the traditional fixed
      needle template. Direct control of real-time imaging aids visualization of the
      needle as it is manually inserted through the guide. Results from in-scanner
      phantom experiments are provided.

PMID- 16404031
TI  - Polymer film based sensor networks for non-invasive medical monitoring.
AB  - An instrumentation system based upon laminate polymer film composition with
      embedded ultra-flat imaging sensors has been designed for application to both
      external and internal monitoring during medical procedures or post-operative
      care. This technology is based upon a common architecture employing PET
      (polyethelene terephthalate) film substrates laminated with conductive printed
      circuit logic and the inclusion of discrete ultra-flat imaging sensors which are
      based upon the principle of compound eye vision. The system enables the
      construction of variable-size, variable-geometry sheets that can be applied
      physically to different locations including objects in an environment that
      requires frequent monitoring.

PMID- 16404032
TI  - Detecting trigger points and irreversibility thresholds in shock and trauma.
AB  - We investigate the model of unstable recurrent patterns within chaotic and highly
      turbulent systems as a possible avenue for linking shifts in parameters that can
      be indicators of nonlinear and irreversible transitions leading to mortality. The
      argument presented is that in the case of mass injury and trauma events from
      natural or intentional causes, large numbers of people may be in situations where
      clinical testing infrastructures have been disabled or destroyed, further
      reducing the ability of medical caregivers to accurately notice indicators and
      signals of impending critical and irreversible conditions. Identification of a
      reduced set of observables that can be linked with unstable yet recurrent
      patterns may provide a means for improved monitoring and life support under such
      adverse conditions.

PMID- 16404033
TI  - A haptic VR milling surgery simulator--using high-resolution CT-data.
AB  - A haptic virtual reality milling simulator using high resolution volumetric data
      is presented in this paper. We discuss the graphical rendering performed from an
      iso-surface generated using marching cubes with a hierarchical storage method to
      optimize for fast dynamic changes to the data during the milling process. We also
      present a stable proxy-based haptic algorithm used to maintain a tip position on
      the surface avoiding haptic fall-through.

PMID- 16404034
TI  - Virtual reality thread simulation for laparoscopic suturing training.
AB  - The level of realism in virtual reality trainers might not be proportional to its
      didactic value. As an example, three exercises to train suturing skills are
      proposed in this article. They use a discrete thread model with a simple but good
      enough behaviour, and constitute a training means for three laparoscopic skills:
      (1) Accurate grasping, which trains grasping a precise point in the thread. (2)
      Coordinated Pulling, which trains tightening the thread co-ordinately and in
      different space orientations; and (3) Knotting, which allow the surgeon to
      practice this manoeuvre. These three exercises, found interesting among experts
      in surgical training, are now being validated in MIS workshops at the Minimally
      Invasive Surgery Centre of Caceres (Spain).

PMID- 16404035
TI  - MRI image overlay: applications to arthrography needle insertion.
AB  - Magnetic Resonance Imaging (MRI) has unmatched potential for planning, guiding,
      monitoring and controlling interventions. MR arthrography (MRA) is the imaging
      gold standard to assess small ligament and fibrocartilage injury in joints. In
      contemporary practice, MRA consists of two consecutive sessions: 1) an
      interventional session where a needle is driven to the joint space and gadolinium
      contrast is injected under fluoroscopy or CT guidance. 2) A diagnostic MRI
      imaging session to visualize the distribution of contrast inside the joint space
      and evaluate the condition of the joint. Our approach to MRA is to eliminate the
      separate radiologically guided needle insertion and contrast injection procedure
      by performing those tasks on conventional high-field closed MRI scanners. We
      propose a 2D augmented reality image overlay device to guide needle insertion
      procedures. This approach makes diagnostic high-field magnets available for
      interventions without a complex and expensive engineering entourage.

PMID- 16404036
TI  - Control system architecture for a minimally invasive surgical robot.
AB  - As the field of surgical robotics continues to evolve, it is important to keep
      patient safety in mind. This paper describes a safety control architecture aimed
      at moving an experimental system in the direction of intrinsically safe
      operation. The system includes safety features such as: a small number of states,
      Programmable Logic Controller (PLC) state transition control, active enable,
      brakes, E-STOP, and a surgeon foot pedal.

PMID- 16404037
TI  - Metrics for an interventional radiology curriculum: a case for standardisation?
AB  - Interventional radiology training and assessment would benefit greatly from the
      introduction of simulation. Assessment methods should facilitate the highest
      standards of training and therefore must be chosen on the basis of evidence of
      impact on learning. A study of assessment in a training model shows the need for
      specialty specific metrics which were derived from a task analysis of
      interventional procedures.

PMID- 16404038
TI  - Surgical Multimedia Academic, Research and Training (S.M.A.R.T.) tool: a
      comparative analysis of cognitive efficiency for two multimedia learning
      interfaces that teach the pre-procedural processes for carpal tunnel release.
AB  - This study proposes a series of guidelines for designing multimedia educational
      interfaces that combine educational strategies with cognitive load theory. There
      is a large body of research that confirms multimedia education is at least as
      effective as the traditional approach, but there is no discussion regarding the
      effectiveness of the interface design. This trial compares two interfaces to
      determine which design techniques are most cognitively efficient for the learner.

PMID- 16404039
TI  - The use of a GripForce system to map force distribution patterns of laparoscopic
      instruments.
AB  - While it is acknowledged that the forces required to manipulate laparoscopic
      instruments can be significant and are important in terms of potential discomfort
      after prolonged use, no systematic study has been conducted. In this paper we
      present a GripForce system that allows for the mapping of force distribution
      patterns of laparoscopic instruments. Initial results showed significant
      differences in force distribution between various instrument handles, thus
      demonstrating the viability of the system and proposed methodology. Analysis of
      force distribution patterns of laparoscopic instruments can help towards
      improving instrument design, better understanding the relationship between force
      applied and performance, as well as provide useful feedback to trainees and
      surgeons.

PMID- 16404040
TI  - Highly-realistic, immersive training environment for hysteroscopy.
AB  - The primary driving application of our current research is the development of a
      generic surgical training simulator for hysteroscopy. A key target is to go
      beyond rehearsal of basic manipulative skills, and enable training of procedural
      skills like decision making and problem solving. In this respect, the sense of
      presence plays an important role in the achievable training effect. To enable
      user immersion into the training environment, the surrounding and interaction
      metaphors should be the same as during the real intervention. To this end, we
      replicated an OR in our lab, provided standard hysteroscopic tools for
      interaction, and generate a new virtual scene for every session. In this setting,
      the training starts, as soon as the trainees enter the OR, and ends when they
      leave the room.

PMID- 16404041
TI  - PelvicSim--a computational-experimental system for biomechanical evaluation of
      female pelvic floor organ disorders and associated minimally invasive
      interventions.
AB  - In this paper we describe the prototype of a new computational simulation system,
      PelvicSim. This system is being developed to simulate the in vivo biomechanics of
      the female pelvic floor organ system with the intent to provide clinical
      researchers, medical device designers with a virtual environment to understand
      the various biomechanical pathologies occurring in the pelvic floor. This
      information can then be used to develop new reconstructive surgical techniques,
      or design non surgical/surgical devices for the treatment of urinary incontinence
      and pelvic organ prolapse. In this paper, we provide the initial results from the
      development of the PelvicSim modules which combine in vivo sensing experiments,
      Ultrasound and MRI imaging datasets, and an inverse finite element modeling
      technology based on hyperviscoelastic constitutive modeling of the pelvic floor
      organs and tissues.

PMID- 16404042
TI  - Working memory and image guided surgical simulation.
AB  - We report on a study that investigates the relationship between visual working
      memory and verbal working memory and a performance measure in endoscopic
      instrument navigation in MIST and GI Mentor II (a simulator for gastroendoscopy).
      Integrated cognitive neuroscience in state-of-the-art simulator training
      curriculum will take safety science in health care one step ahead. Current
      simulator validation focuses on how to train. In the light of recent research it
      is now prime time to ask why in search of mechanisms rather than to repeatedly
      show that training has effect. This will help tailor training to maximize
      individual output in procedures that require a high level of dexterity. WM
      training is a unique learning aid in simulator training and should be used
      alongside clinical practice in order to improve the quality of complex clinical
      intervention in the field of image guided surgical simulation.

PMID- 16404043
TI  - Virtual acupuncture human based on chinese visible human dataset.
AB  - In this paper, we present our application of latest information technology in
      assisting the Chinese acupuncture research. Having integrated the Chinese Visible
      Human (CVH) data, virtual reality, visualization and imaging techniques, we have
      constructed a 3-dimensional digital human model for acupuncture. This model
      integrates the meridian positioning, acupoint positioning, arbitrary cutting
      plane visualization, multi-layer dissection, needle puncturing simulation, as
      well as the common diseases-therapy information. Our work can be widely applied
      to Chinese acupuncture education, clinical usage and scientific research.

PMID- 16404044
TI  - Visualization of a stationary CPG-revealing spinal wave.
AB  - Central Pattern Generator (CPG) is still an elusive concept that has a visual
      manifestation as a rhythmic oscillation commanded from the spine, but that also
      has another manifestation as a train of bursts in the surface electromyographic
      (sEMG) signals recorded on the para-spinal muscles. This leads to the challenging
      problem of correlating the visually observed spinal wave with the sEMG signals
      recorded during the session. This paper develops a mathematical model of the
      spinal wave phenomenon, which, when driven by the sEMG data, yields such visually
      observable features as wave nodes.

PMID- 16404045
TI  - Establishing navigated control in head surgery.
AB  - Navigated Control (NC) describes an additional control for a tracked power driven
      instrument within a preoperatively segmented work space. In head surgery the
      authors first implemented NC in functional endoscopic sinus surgery (FESS).
      Recently the feasibility of NC for surgery on the petrosal bone is evaluated. NC
      in FESS and in petrosal bone surgery may reduce the risk of comorbidity and the
      time effort compared to the conventional surgical interventions.

PMID- 16404046
TI  - Can augmented force feedback facilitate virtual target acquisition tasks?
AB  - This study investigates facilitation of a manual target acquisition task by the
      application of appropriate force feedback through the control device (e.g.,
      mouse, joystick, trackball). Typical manual movements with these devices were
      measured, and models of such movements were used to predict an intended target
      location from an initial portion of a trace. Preferred shapes and sizes for
      feedback force functions to be applied were empirically determined by collecting
      preference ratings and measuring task completion times. The general experimental
      task that is typical for an office situation, but findings appear generalizable
      to some medical and surgical situations (e.g. laparoscopy, catheterization) where
      a certain target has to be reached whose precise location may be known or
      unknown.

PMID- 16404047
TI  - Effectiveness of haptic feedback in open surgery simulation and training systems.
AB  - This paper presents progress in the development of an untethered haptic feedback
      system for open surgery simulation and training being developed by Energid
      Technologies. A key innovation in our simulation is an untethered haptic feedback
      method. In this paper, we describe our approach to developing an effective
      untethered haptic feedback system, and our current progress. We also present the
      results of a haptic feedback effectiveness study which explores how haptic
      rendering accuracy behaves as a function of sampling rate for tool tracking.

PMID- 16404048
TI  - A flexible infrastructure for delivering augmented reality enabled transcranial
      magnetic stimulation.
AB  - Transcranial Magnetic Stimulation (TMS) is the process in which electrical
      activity in the brain is influenced by a pulsed magnetic field. Common practice
      is to align an electromagnetic coil with points of interest identified on the
      surface of the brain, from an MRI scan of the subject. The coil can be tracked
      using optical sensors, enabling the targeting information to be calculated and
      displayed on a local workstation. In this paper we explore the hypothesis that
      using an Augmented Reality (AR) interface for TMS will improve the efficiency of
      carrying out the procedure. We also aim to provide a flexible infrastructure that
      if required, can seamlessly deploy processing power from a remote high
      performance computing resource.

PMID- 16404049
TI  - Fast assessment of acetabular coverage using stereoscopic volume rendering.
AB  - Previous CT-based methods of measuring acetabular coverage of the femoral head
      have either been labor-intensive or have required extensive preprocessing of the
      data prior to visualization. We propose a method of measuring acetabular coverage
      using stereoscopic digitally reconstructed radiographs that required very little
      labor or image preprocessing time. Taking a craniocaudal view of the pelvis, we
      measured both preoperative and postoperative CTs of 10 patients treated with
      transtrochanteric periacetabular osteotomy. Measurements were then made in both
      monocular and stereoscopic rendering modes. Our method is fast, easy, and
      provides an intuitive means of visualizing an orthopedic parameter that is
      important in the progression of early hip arthritis.

PMID- 16404050
TI  - Ballistic injury simulation using the material point method.
AB  - The Material Point Method is used in the computational simulation of ballistic
      projectile damage to the heart. A transversely isotropic hyperelastic material
      model is used to model the myocardium. Computed estimates of tissue damage are
      used to characterize damaged tissue. The method's potential to estimate the
      damaged tissue in the complete torso is considered.

PMID- 16404051
TI  - Use of surgical videos for realistic simulation of surgical procedures.
AB  - One of the major challenges in the development of virtual environments for
      medical simulations is photorealistic rendering, permitting high fidelity visual
      effects and user interaction. Digitized videos recorded from the laparoscopic
      camera are a rich source of information about surgical scenarios. How to fully
      utilize the information is important for improving the realism of the simulated
      scenarios. In reality, the camera viewpoint changes frequently and even for the
      same viewpoint, the scene is dynamic due to rhythmic heartbeat. Hence, the
      results of classical texture mapping are usually visually unappealing as they
      fail to capture the pulsatile effect, as well as other global illumination
      properties of the scene. In this paper we present a hybrid technique to improve
      the photorealistic rendering of the virtual surgery scenarios by spatio
      temporally utilizing videos recorded during actual surgical procedures.

PMID- 16404052
TI  - Pulse!!--A virtual learning space project.
AB  - Game-based technology structured within an epistemic framework is revolutionizing
      learning. Intersecting military simulation technologies with modern pedagogical
      education practices, Pulse!! offers an epistemic framework for optimizing
      cognitive and psychomotor skills in clinical practices. Its intelligent authoring
      system is an integrated, fully immersive, interactive virtual learning simulation
      for civilian and military health care practitioners, providing opportunities to
      make mistakes and repeat actions.

PMID- 16404053
TI  - Real-time augmented feedback benefits robotic laparoscopic training.
AB  - Robotic laparoscopic surgery has revolutionized minimally invasive surgery for
      treatment of abdominal pathologies. However, current training techniques rely on
      subjective evaluation. There is a lack of research on the type of tasks that
      should be used for training. Robotic surgical systems also do not currently have
      the ability to provide feedback to the surgeon regarding success of performing
      tasks. We trained medical students on three laparoscopic tasks and provided real
      time feedback of performance during training. We found that real-time feedback
      can benefit training if the feedback provides information that is not available
      through other means (grip force). Subjects that received grip force feedback
      applied less force when the feedback was removed. Other forms of feedback (speed
      and relative phase) did not aid or impede training. Secondly, a relatively short
      training period (10 trials for each task) significantly improved most objective
      measures of performance. We also showed that robotic surgical performance can be
      quantitatively measured and evaluated. Providing grip force feedback can make the
      surgeon more aware of the forces being applied to delicate tissue during surgery.

PMID- 16404054
TI  - Computer-aided forensics: metal object detection.
AB  - Recently, forensic investigators1 have started using diagnostic radiology devices
      (MRI, CT) to acquire image data from cadavers. This new technology, called the
      virtual autopsy, has the potential to provide a low cost, non-invasive
      alternative or supplement to conventional autopsies. New image processing
      techniques are being developed to highlight forensically relevant information in
      the images. One such technique is the detection and characterization of metal
      objects embedded in the cadaver. Analysis of this information across a population
      with similar causes of death can lead to developing improved safety and
      protection devices with a corresponding reduction in deaths.

PMID- 16404055
TI  - Parametric modeling and simulation of trocar insertion.
AB  - Trocar insertion, the first step to most micro surgery procedures is a difficult
      procedure to learn and practice because procedure is carried out almost entirely
      without any visual feedback of the organs underlying the tissue being punctured.
      A majority of injuries is attributed to the excessive use of force by the
      surgeon. This paper looks at developing a haptic based trocar insertion simulator
      which will assist in training and skill advancement in carrying out this
      procedure. Different issues regarding development of force model and and trocar
      tissue interaction is studied.

PMID- 16404056
TI  - Exploiting graphics hardware for haptic authoring.
AB  - Real-time, plausible visual and haptic feedback of deformable objects without
      shape artifacts is important in surgical simulation environments to avoid
      distracting the user. We propose to leverage highly parallel stream processing,
      available on the newest generation graphics cards, to increase the level of both
      visual and haptic fidelity. We implemented this as part of the University of
      Florida's haptic surgical authoring kit.

PMID- 16404057
TI  - An interactive stereoscopic display for cooperative work--volume visualization
      and manipulation with multiple users.
AB  - A stereoscopic display table for cooperative work with a volume data is
      described. Adequate stereoscopic image generated from the volume data is
      displayed and shared by multiple users. All the users can observe and interact
      with the volume data displayed on the IllusionHole in a face-to-face environment.
      It displays each pair of stereoscopic images such that all users observe the 3D
      image at exactly the same position. An outline of the system is described in this
      paper.

PMID- 16404058
TI  - 3D Live-Wires on mosaic volumes.
AB  - The paper discusses the first evaluation of a 3D Live-Wire technique that
      operates on over-segmented 3D mosaic volumes. Pre-processing normalizes data by
      histogram spreading followed by over-segmentation with region growing. This leads
      to a robust and intuitive parameter selection for various tissues and image
      modalities without requiring problem specific knowledge. During interactive
      segmentation from a set of user-defined seed points a triangle mesh using
      Delaunay triangulation is generated. For each triangle, defined by three seed
      points, a closed surface patch is generated by the 3D Live-Wire method. For
      evaluation purpose white cerebral matter from MRI images is to be segmented. A
      mean deviation from the correct object boundary extracted from available model
      data of about 0.60 pixels (+/- 0.23) is observed while the required time was
      about 229.5 seconds (+/- 173.2).

PMID- 16404059
TI  - Surgical PACS for the digital operating room. Systems engineering and
      specification of user requirements.
AB  - For better integration of surgical assist systems into the operating room, a
      common communication and processing plattform that is based on the users needs is
      needed. The development of such a system, a Surgical Picture Aquisition and
      Communication System (S-PACS), according the systems engineering cycle is oulined
      in this paper. The first two steps (concept and specification) for the
      engineering of the S-PACS are discussed.A method for the systematic integration
      of the users needs', the Quality Function Deployment (QFD), is presented. The
      properties of QFD for the underlying problem and first results are discussed.
      Finally, this leads to a first definition of an S-PACS system.

PMID- 16404060
TI  - Smooth vasculature reconstruction with circular and elliptic cross sections.
AB  - This paper presents a method to segment and reconstruct vascular structure from
      patient volumetric scan. First, a semi-automatic segmentation phase leads to the
      vessels centerlines and the estimated circular or elliptic cross section
      description. Then, the skeleton data are used by the reconstruction phase to
      generate the three dimensional vascular surface. This structured surface is able
      to handle interactive visualization, real-time and robust physics-based modeling.
      The accuracy and consistency of our technique are evaluated on a vascular phantom
      as well as two clinical data sets. Experiments show that the proposed technique
      reaches a good balance in terms of mesh smoothness, compactness, and accuracy,
      where elliptic cross section estimation induces lower error.

PMID- 16404061
TI  - Towards a VR trainer for EVAR treatment.
AB  - Endovascular repair of aortic abdominal aneurysms (AAA) is more and more becoming
      part of clinical practice. Up to approximately 30 clinical procedures however are
      necessary to obtain the surgical skills to make the procedure reliable and safe.
      The current study aims to generate a VR trainer to speed up the training process
      of experienced vascular surgeons to become experienced EVAR (endovascular AAA
      repair) surgeons by introducing a VR environment. This manuscript describes the
      contents and validation of the first step in the VREST - EVAR trainer, i.e. the
      proper definition of the knowledge and skills that need to be transferred.

PMID- 16404062
TI  - Gestalt operating room display design for perioperative team situation awareness.
AB  - The perioperative environment is a complex, high risk environment that requires
      real-time coordination by all perioperative team members and accurate, up-to-date
      information for situation assessment and decision-making. There is the need for a
      "Gestalt" holistic awareness of the perioperative environment to enable synthesis
      and contextualization of the salient information such as: patient information,
      case and procedure information, staff information, operative site view,
      physiological data, resource availability. One potential approach is to augment
      the medical toolkit with a large screen wall display that integrates and makes
      accessible information that currently resides in different data systems and care
      providers. The objectives are to promote safe workflows, team coordination and
      communication, and to enable diagnosis, anticipation of events, and information
      flow from upstream to downstream care providers. We used the human factors
      engineering design process to design and develop a display that provides a common
      operational picture for shared virtual perioperative team situation awareness to
      enhance patient safety.

PMID- 16404063
TI  - Integrating surgical robots into the next medical toolkit.
AB  - Surgical robots hold much promise for revolutionizing the field of surgery and
      improving surgical care. However, despite the potential advantages they offer,
      there are multiple barriers to adoption and integration into practice that may
      prevent these systems from realizing their full potential benefit. This study
      elucidated some of the most salient considerations that need to be addressed for
      integration of new technologies such as robotic systems into the operating room
      of the future as it evolves into a complex system of systems. We conducted in
      depth interviews with operating room team members and other stakeholders to
      identify potential barriers in areas of workflow, teamwork, training, clinical
      acceptance, and human-system interaction. The findings of this study will inform
      an approach for the design and integration of robotics and related computer
      assisted technologies into the next medical toolkit for "computer-enhanced
      surgery" to improve patient safety and healthcare quality.

PMID- 16404064
TI  - Study of laparoscopic forces perception for defining simulation fidelity.
AB  - One of the most controversial dilemmas in virtual reality laparoscopic simulators
      design is the incorporation of force feedback (FF). This issue is approached with
      an experimental design in which surgeons assess the resistance against pulling of
      four different tissues, which are characterized with the acquisition of
      interaction forces. Comparing subjective assessments with objective force
      parameters we aim to determine the fidelity boundary beyond which no more realism
      is necessary in simulation. Interaction pulling forces of four tissues have been
      characterized, which can constitute a basis for requirements of a FF algorithm.
      Results have also led to the hypothesis that surgeons are able to differentiate
      tissues and perceive somesthesic information although resulting interaction
      forces are of the same magnitude than interferences like trocar friction.

PMID- 16404065
TI  - Computer prediction of balloon angioplasty from artery imaging.
AB  - The success of angioplasty depends on a balance between two conflicting
      objectives: maximization of artery lumen patency and minimization of mechanical
      damage. A finite element model for the patient-specific prediction of angioplasty
      is proposed as a potential tool to assist clinicians. This paper describes the
      general methodology and the algorithm that computes device/artery friction work
      during balloon insertion and deployment. The potential of the model is
      demonstrated with examples that include artery model reconstruction and
      prediction of friction on the arterial wall during balloon insertion and
      deployment.

PMID- 16404066
TI  - Efficient topology modification and deformation for finite element models using
      condensation.
AB  - Cuts on deformable organs are a central task in the set of physical operations
      needed in many surgical simulation environments. Our BioMedIA surgical simulator
      structures are Finite Element Models, driven by displacements on the touched
      nodes as opposed to forces. This approach allows for realistic simulation of both
      deformation and haptic response at real-time rates. The integration of
      condensation into our system increases its efficiency, and allows for complex
      interaction on larger meshes than would normally be permitted with available
      memory. We present an extension of our novel algorithm for cuts in deformable
      organs, in the context of condensed matrices. We show results from our surgical
      simulation system with real-time haptic feedback.

PMID- 16404067
TI  - Physics-based models for catheter, guidewire and stent simulation.
AB  - For over 20 years, interventional methods have improved the outcomes of patients
      with cardiovascular disease or stroke. However, these procedures require an
      intricate combination of visual and tactile feedback and extensive training
      periods. An essential part of this training relates to the manipulation of
      diagnostic and therapeutic devices such as catheters, guidewires, or stents. In
      this paper, we propose a physics-based model of wire-like structures that can be
      used as a core representation for the real-time simulation of various devices.
      Our approach is computationally efficient, and physically realistic. A
      catheter/guidewire is simulated using a composite model, which can dynamically
      adapt its material properties to locally describe a combination of both devices.
      We also show that other devices, such as stents, can be modeled from the same
      core representation.

PMID- 16404068
TI  - A web-based repository of surgical simulator projects.
AB  - The use of computer-based surgical simulators for training of prospective
      surgeons has been a topic of research for more than a decade. As a result, a
      large number of academic projects have been carried out, and a growing number of
      commercial products are available on the market. Keeping track of all these
      endeavors for established groups as well as for newly started projects can be
      quite arduous. Gathering information on existing methods, already traveled
      research paths, and problems encountered is a time consuming task. To alleviate
      this situation, we have established a modifiable online repository of existing
      projects. It contains detailed information about a large number of simulator
      projects gathered from web pages, papers and personal communication. The database
      is modifiable (with password protected sections) and also allows for a simple
      statistical analysis of the collected data. For further information, the surgical
      repository web page can be found at www.virtualsurgery.vision.ee.ethz.ch.

PMID- 16404069
TI  - GiPSiNet: an open source/open architecture network middleware for surgical
      simulations.
AB  - In this paper, we present the design and techniques of GiPSiNet, an open
      source/open architecture network middleware being developed for surgical
      simulations. GiPSiNet extends GiPSi (General Interactive Physical Simulation
      Interface), our framework for developing organ level surgical simulations, to
      network environments. This network extension is non-trivial, since the network
      settings pose several serious problems for distributed surgical virtual
      environments such as band-width limit, delays, and packet losses. Our goal is to
      enhance the quality (fidelity and realism) of networked simulations in the
      absence of network QoS (Quality of Service) through the GiPSiNet middleware.

PMID- 16404070
TI  - Measurement of the mechanical response of intra-abdominal organs of fresh human
      cadavers for use in surgical simulation.
AB  - Determination of soft tissue properties is essential for the realism of the
      virtual scenarios. The major challenge is that soft tissues exhibit complicated
      mechanical properties including viscoelastic, nonlinear, inhomogeneous, and rate
      dependent behaviors. Measurements on live human patients present significant
      risks, thus making the use of cadavers a logical alternative. Cadavers are widely
      used in present day surgical training, are relatively easy to procure through
      excellent donor programs and have the right anatomy, which makes them better
      candidates for training than the porcine model. To investigate the static and
      dynamic properties of soft tissue, we have developed a high precision tactile
      stimulator by modifying an existing haptic interface device, the Phantom, and
      used it to record the force-displacement behavior of intra-abdominal organs of
      fresh human cadavers at the US Surgical facility in Connecticut and Albany
      Medical College.

PMID- 16404071
TI  - A VR planning system for craniosynostosis surgery.
AB  - The goal of our project is to build a system which could utilize the Virtual
      Reality (VR) techniques for the pre-operative planning of craniosynostosis. The
      system includes different modules. We use the tetrahedral volume meshes for the
      basic structure for the models which surgery is planning on. This paper will
      describe the procedures of above stages, from the processing of 2D image slices,
      3D modeling, smoothing, simplification, and visibility ordering, to volume meshes
      generation. We have demonstrated the initial results on a variety of stereo
      devices. The testing results show the processing time is acceptable and the
      rendering effect is pretty well.

PMID- 16404072
TI  - Real-time finite element based virtual tissue cutting.
AB  - Tool-tissue interaction is most accurately modeled as an imposed displacement
      constraint, thus augmenting the traditional finite element equation, Ku=f, to a 2
      x 2 block system. This augmentation does two things: it enlarges the system, and
      it introduces the Schur complement(S) during the solution. This research has
      focused on efficient methods to update the Schur complement and it's inverse
      during displacement constraint removal and addition to allow for soft-tissue
      cutting to occur in real-time. By taking advantage of how the constraints impact
      the Schur complement, removal and addition of these constraints are handled by
      either performing a rank-2 or rank-1 update on S(-1), respectively. This greatly
      reduces the computational load on the CPU; and through use of timing tests shows
      that the update frequencies are well within an acceptable range for tactile
      feedback. To further solidify this method as being highly useful, a prototypical
      simulator has been developed that allows users to haptically perform bi-manual
      soft-tissue cutting.

PMID- 16404073
TI  - The design and implementation of a pulmonary artery catheterization simulator.
AB  - Pulmonary Artery Catheterization (PAC) is a commonly performed procedure. It is
      used when hemodynamic and other cardiac measures must be accurately monitored in
      seriously ill patients. A flow-directed, balloon-tipped (Swan-Ganz) catheter is
      typically inserted into a major vein, passed through the heart, and into the
      pulmonary artery. This procedure is normally not performed under fluoroscopy.
      Instead, transducer readings from the catheter tip provide a continuous report of
      local blood pressure. An experienced practitioner can infer the catheter's
      location from this information, yet several studies have found that physicians
      and critical care nurses have a wide variability in competency. A simulator for
      this procedure can address some of the educational and training issues
      highlighted. This paper describes our ongoing progress in developing a PAC
      trainer.

PMID- 16404074
TI  - Flat maps: a multi-layer parameterization for surgery simulation.
AB  - Modeling organs for surgery simulation is a formidable challenge due to two
      reasons. First, the organs and body parts have not only very complex shapes, but
      are deformable too. The second challenge is to provide a mechanism for surgeons
      to interact with these complex anatomical objects. We present a novel multi-layer
      parameterized representation scheme that addresses the both challenges. In our
      approach, we use a 2D flat map representation for the 3D geometry of the organ,
      that can be used for rendering, collision detection, and deformation. The tool
      organ interaction can be computed on the 2D flat maps and then mapped back to the
      3D geometry of the organs. With this representation, we demonstrate that we can
      construct a practical and realistic environment for interactive surgery
      simulation.

PMID- 16404075
TI  - Second generation haptic ventriculostomy simulator using the ImmersiveTouch
      system.
AB  - Ventriculostomy is a neurosurgical procedure that consists of the insertion of a
      catheter into the ventricles of the brain for relieving the intracranial
      pressure. A distinct "popping" sensation is felt as the catheter enters the
      ventricles. Early ventriculostomy simulators provided some basic audio/visual
      feedback to simulate the procedure, displaying a 3D virtual model of a human
      head. Without any tactile feedback, the usefulness of such simulators was very
      limited. The first generation haptic ventriculostomy simulators incorporated a
      haptic device to generate a virtual resistance and "give" upon ventricular entry.
      While this created considerable excitement as a novelty device for cannulating
      ventricles, its usefulness for teaching and measuring neurosurgical expertise was
      still very limited. Poor collocation between the haptic device stylus held by the
      surgeon and the visual representation of the virtual catheter, as well as the
      lack of a correct viewer-centered perspective, created enormous confusion for the
      neurosurgeons who diverted their attention from the actual ventriculostomy
      procedure to overcoming the limitations of the simulator. We present a second
      generation haptic ventriculostomy simulator succeeding over the major first
      generation limitations by introducing a head and hand tracking system as well as
      a high-resolution high-visual-acuity stereoscopic display to enhance the
      perception and realism of the virtual ventriculostomy.

PMID- 16404076
TI  - Hybrid analysis of a spherical mechanism for a minimally invasive surgical (MIS)
      robot--design concepts for multiple optimizations.
AB  - Several criteria exist for determining the optimal design for a surgical robot.
      This paper considers kinematic performance metrics, which reward good kinematic
      performance, and dynamic performance metrics, which penalize poor dynamic
      performance. Kinematic and dynamic metrics are considered independently, and then
      combined to produce hybrid metrics. For each metric, the optimal design is the
      one that maximizes the performance metric over a specific design space. In the
      case of a 2-DOF spherical mechanism for a surgical robot, the optimal design
      determined by kinematic metrics is a robot arm with link angles (alpha(12)=90
      degrees , alpha(23)=90 degrees ). The large link angles are the most dextrous,
      but have the greatest risk of robot-robot or robot-patient collisions and require
      the largest actuators. The link lengths determined by the dynamic metrics are
      much shorter, which reduces the risk of collisions, but tend to place the robot
      in singularities much more frequently. When the hybrid metrics are used, and a
      restriction that the arm must be able to reach a human's entire abdomen, the
      optimal design is around (alpha(12)=51 degrees, alpha(23)=54 degrees). The hybrid
      design provides a compromise between dexterity and compactness.

PMID- 16404077
TI  - Data mining of the E-pelvis simulator database: a quest for a generalized
      algorithm for objectively assessing medical skill.
AB  - Inherent difficulties in evaluating clinical competence of physicians has lead to
      the widespread use of subjective skill assessment techniques. Inspired by an
      analogy between medical procedure and spoken language, proven modeling methods in
      the field of speech recognition were adapted for use as objective skill
      assessment techniques. A generalized methodology using Markov Models (MM) was
      developed. The database under study was collected with the E-Pelvis physical
      simulator. The simulator incorporates an array of five contact force sensors
      located in key anatomical landmarks. Two 32-state fully connected MMs are used,
      one for each skill level. Each state in the model corresponds to one of the
      possible combinations of the 5 active contact force sensors distributed in the
      simulator. Statistical distances measured between models representing subjects
      with different skill levels are sensitive enough to provide an objective measure
      of medical skill level. The method was tested with 41 expert subjects and 41
      novice subjects in addition to the 30 subjects used for training the MM. Of the
      82 subjects, 76 were classified correctly (92%). Moreover, unique state
      transitions as well as force magnitudes for corresponding states (expert/novice)
      were found to be skill dependent. Given the white box nature of the model,
      analyzing the MMs provides insight into the examination process performed. This
      methodology is independent of the modality under study. It was previously used to
      assess surgical skill in a minimally invasive surgical setup using the Blue
      DRAGON, and it is currently applied to data collected using the E-Pelvis.

PMID- 16404078
TI  - Segmenting the visible human female.
AB  - Web-based three-dimensional Virtual Body Structures (W3D-VBS) is an interactive
      image-based anatomical training system over the Internet. It uses segmented low
      resolution Visible Human Male (LR-VHM) data to dynamically explore, select,
      highlight, label, extract, manipulate, and stereoscopically palpate 3D virtual
      anatomical models with a haptic device. The segmentation results presented in
      this paper for the Visible Human Female (VHF) and the high resolution Visible
      Human Male (HR-VHM) have been obtained using our segmentation tools. Segmenting
      the HR-VHM was an easier task as we use the segmented shapes and label
      information of existing LR-VHM data, with the same image content. This is not the
      case for the VHF and we needed to develop a special tool, Segm-VHF, which allows
      us to integrate the VHF dataset into W3D-VBS.

PMID- 16404079
TI  - A discrete soft tissue model for complex anatomical environment simulations.
AB  - Among the current challenges in human soft tissue modeling for medical purposes,
      the ability to model complex anatomical structures, their interactions and to
      accurately simulate them with physical realism are in the forefront of research.
      This paper describes a discrete soft tissue model which is geared toward solving
      these challenges. In this model, objects can be described as volumetric or
      surfacic sets of nodes depending on the level of precision required. Nodes have
      their own physical properties and a definition of their neighborhood. All these
      objects are submitted both to internal cohesive forces and to external attractive
      or interaction forces with other objects. Volume preservation is insured by a
      constraint. The model is applied to the simulation of the prostate and its
      surrounding organs.

PMID- 16404080
TI  - Image-guided laser projection for port placement in minimally invasive surgery.
AB  - We present an application of an augmented reality laser projection system in
      which procedure-specific optimal incision sites, computed from pre-operative
      image acquisition, are superimposed on a patient to guide port placement in
      minimally invasive surgery. Tests were conducted to evaluate the fidelity of
      computed and measured port configurations, and to validate the accuracy with
      which a surgical tool-tip can be placed at an identified virtual target. A high
      resolution volumetric image of a thorax phantom was acquired using helical
      computed tomography imaging. Oriented within the thorax, a phantom organ with
      marked targets was visualized in a virtual environment. A graphical interface
      enabled marking the locations of target anatomy, and calculation of a grid of
      potential port locations along the intercostal rib lines. Optimal configurations
      of port positions and tool orientations were determined by an objective measure
      reflecting image-based indices of surgical dexterity, hand-eye alignment, and
      collision detection. Intra-operative registration of the computed virtual model
      and the phantom anatomy was performed using an optical tracking system. Initial
      trials demonstrated that computed and projected port placement provided direct
      access to target anatomy with an accuracy of 2 mm.

PMID- 16404081
TI  - Planning and analyzing robotized TMS using virtual reality.
AB  - Transcranial Magnetic Stimulation (TMS) is a powerful method to examine the brain
      and non-invasively treat disorders of the central nervous system. Magnetic
      stimulation of the motor cortex results in the activation of corresponding muscle
      groups. Hereby, accurate placement of the TMS coil to the patient's head is
      crucial to successful stimulation. We developed a way to position the TMS coil
      using a robot and navigate it in virtual reality based on an online registration
      of the cranium relative to 3D magnetic resonance imaging data. By tracking the
      head and robotic motion compensation, fixation of the patient's head becomes
      obsolete. Furthermore, a novel method for motor cortex mapping is presented. The
      robotized TMS system is used to obtain the characteristic field of a TMS coil.
      This field is registered to the field of motor evoked potential measurements at
      the patient's head to yield a prediction of the motoric center of a target
      muscle.

PMID- 16404082
TI  - Medical student evaluation using augmented standardized patients: preliminary
      results.
AB  - Standardized patients (SPs), individuals trained to realistically portray
      patients, are commonly used to teach and assess medical students. The range of
      clinical problems an SP can portray, however, is limited. They are typically
      healthy individuals with few or no abnormal physical findings. We have developed
      a functioning prototype that uses sound-based augmented reality to expand the
      capabilities of an SP to exhibit physically-manifested abnormalities. The primary
      purpose of this paper is to describe this prototype and report on its use in a
      study using medical students evaluated in a required annual Observed Structured
      Clinical Examination (OSCE). Presented is an overview of the prototype, a
      detailed description of the study, final results from the study, and conclusions
      drawn about the validity of using augmented SPs as a reliable medical assessment
      tool.

PMID- 16404083
TI  - Direct volumetric rendering based on point primitives in OpenGL.
AB  - The aim of this project is to present a renderization by software algorithm of
      acquired volumetric data. The algorithm was implemented in Java language and the
      LWJGL graphical library was used, allowing the volume renderization by software
      and thus preventing the necessity to acquire specific graphical boards for the 3D
      reconstruction. The considered algorithm creates a model in OpenGL, through point
      primitives, where each voxel becomes a point with the color values related to
      this pixel position in the corresponding images.

PMID- 16404084
TI  - A haptic device for guide wire in interventional radiology procedures.
AB  - Interventional Radiology (IR) is a minimally invasive procedure where thin
      tubular instruments, guide wires and catheters, are steered through the patient's
      vascular system under X-ray imaging. In order to perform these procedures, a
      radiologist has to be trained to master hand-eye coordination, instrument
      manipulation and procedure protocols. The existing simulation systems all have
      major drawbacks: the use of modified instruments, unrealistic insertion lengths,
      high inertia of the haptic device that creates a noticeably degraded dynamic
      behavior or excessive friction that is not properly compensated for. In this
      paper we propose a quality training environment dedicated to IR. The system is
      composed of a virtual reality (VR) simulation of the patient's anatomy linked to
      a robotic interface providing haptic force feedback. This paper focuses on the
      requirements, design and prototyping of a specific haptic interface for guide
      wires.

PMID- 16404085
TI  - Computer-aided navigation for arthroscopic hip surgery using encoder linkages for
      position tracking.
AB  - While arthroscopic surgery has many advantages over traditional surgery, this
      minimally invasive surgical technique is not often applied to the hip joint.
      There are two main reasons for this: the difficulties of navigating within the
      joint and of correctly placing portal incisions without damaging critical
      neurovascular structures. This paper proposes a computer-aided navigation system
      to address the challenges of arthroscopic hip surgery. Unlike conventional
      arthroscopic methods, this system uses encoder linkages to track surgical
      instruments, thus eliminating the problems associated with standard tracking
      systems. The encoder position information is used to generate a computer display
      of patient anatomy to supplement the restricted view from a typical arthroscopic
      camera.

PMID- 16404086
TI  - Project hydra--a new paradigm of internet-based surgical simulation.
AB  - Computer-based surgical simulation systems have produced tremendous benefits and
      demonstrated validity as a better method for many areas of surgical skills
      acquisition. However, despite these benefits, broad proliferation of these
      systems has continued to be elusive. While in large part this lag in adoption of
      this technology is due to social factors (organizational momentum, curriculum
      integration difficulties, etc), the cost of computer-based simulation systems has
      certainly remained a major deterrent toward broad deployment. Instead, what if it
      were possible to eliminate the cost of the large computer completely from the
      system, yet provide a much more extensive and detailed simulation than currently
      available? Finally, what if a simulation with even greater detail over a wider
      anatomical area were possible?This is the genesis of Project Hydra- a shared
      simulation supercomputer were made available for free and all that is required to
      access it is a low-end Internet-connected computer and, optionally,
      interaction/haptics devices as needed for the particular task. This would enable
      supercomputer-class simulation at every desktop with much greater fidelity than
      any user could individually afford and provide an online community for simulation
      research and application. Further, Internet-based simulation provides for many
      other benefits as well. By the user merely plugging optional, additional hardware
      into their existing, low-end PC and using the Internet as a means of simulation
      dissemination, distribution, and delivery means that the user can have immediate
      access to simulation updates/upgrades and download/access new content (didactic
      curriculum and cases). Further, this ease of access and use could lead to
      accelerated adoption and use of simulation within the medical curriculum and this
      access is provided anywhere in the world 24 x 7. In addition, once connected, a
      server-based simulation system would be a natural point for performing easy,
      automated clinical studies of surgical performance and skills.

PMID- 16404087
TI  - Fast rigid registration in radiation therapy.
AB  - Based on a stochastic mutual information type matching and RPROP as stochastic
      optimizer, an interactive image-based registration of a CT volume onto two 2D
      images provided by a megavoltage system is presented. The matching process is
      based on semi-automatic pre-segmentation, an approximate 2D-2D matching with
      precomputed virtual projections (DRRs) followed by an accurate 3D-2D matching
      step. Our sample-based approach requires only a fraction of computed DRRs for 3D
      2D. A simultaneous computation of the DRR rays and their perturbations in 6
      dimensions speeds up the rendering process by a factor of 6.8. The complete
      registration process takes 5.6 +/- 2.3 seconds on a 3 GHz Pentium IV PC, being
      the fastest non-parallel approach for this sort of application the authors are
      aware of.

PMID- 16404088
TI  - Can immersive virtual reality reduce phantom limb pain?
AB  - This paper describes the design and implementation of a case-study based
      investigation using immersive virtual reality as a treatment for phantom limb
      pain. The authors' work builds upon prior research which has found the use of a
      mirror box (where the amputee sees a mirror image of their remaining anatomical
      limb in the phenomenal space of their amputated limb) can reduce phantom limb
      pain and voluntary movement to paralyzed phantom limbs for some amputees. The
      present project involves the transposition of movements made by amputees'
      anatomical limb into movements of a virtual limb which is presented in the
      phenomenal space of their phantom limb. The three case studies presented here
      provide qualitative data which provide tentative support for the use of this
      system for phantom pain relief. The authors suggest the need for further research
      using control trials.

PMID- 16404089
TI  - Interactive simulation training: computer simulated standardized patients for
      medical diagnosis.
AB  - SIMmersion LLC is a software development company that creates human interactive
      training simulations. SIMmersion produces PC-based simulations of people with
      whom trainees are able to hold conversations. Trainees communicate with simulated
      characters in face-to-face conversations, using voice recognition technology.
      Topics that would match well with SIMmersion's simulation capabilities include
      diagnosis of depression, alcoholism, or drug use, grievance counseling, marriage
      counseling, suicide intervention, and first responder training for biological
      terrorism. SIMmersion's technology could be integrated with modeling technology
      to create a speech-interactive, mannequin-based patient simulation system for
      healthcare training and assessment. Systems currently being developed involve
      early detection of smallpox as a result of a biological attack.

PMID- 16404090
TI  - Soft-tissue balance evaluation system for total hip arthroplasty by
      intraoperative contact pressure measurement at the hip joint.
AB  - We developed a system for measurement of contact pressure at the hip joint
      surfaces that enables checking of the artificial hip joint condition during
      surgery. First, we constructed the pressure sensor that forms the artificial
      joint. We installed eight small pressure sensors to the spherical head component,
      a part of the ball-socket joint. Next, we developed software for recording and
      visualizing the detected pressures that were recorded every 1 ms. The pressure
      distribution was displayed with the 3D computer graphics in real-time. The system
      enabled intuitive recognition of pressure direction 3-dimensions. Next, using the
      system, we conducted measurements during total hip arthroplasty. Although it
      requires some improvements in its measurement accuracy, the system allows real
      time acquisition of information on the artificial hip joint in real-time. Further
      improvements of the calibration method should enable more accurate measurements.
      As a complete system, it will be a useful tool for selecting an appropriate
      implant that fits a patient's hip joint or for estimating the risk of
      complications after surgery.

PMID- 16404091
TI  - Algorithmically generated music enhances VR nephron simulation.
AB  - While sonification has enjoyed much attention in VR simulation studies, music has
      generally been incorporated as ambiance. This is partially due to difficulties
      with manipulating it interactively in real-time while maintaining a sensible
      musicality. This paper discusses how algorithmically generated music is used to
      provide ambiance, characterize the visual representation of molecular particle
      flow, provide orientation cues to the user, and enhance recognition of chemical
      gradient balances in a reified model of the kidney nephron. The technical
      obstacles related to the use of music in this context are also addressed.

PMID- 16404092
TI  - Haptic device for a ventricular shunt insertion simulator.
AB  - In this paper we propose a new one-degree-of-freedom haptic device that can be
      used to simulate ventricular shunt insertion procedures. The device is used
      together with the BRAINTRAIN training simulator developed for neuroscience
      education, neurological data visualization and surgical planning. The design of
      the haptic device is based on a push-pull cable concept. The rendered forces
      produced by a linear motor connected at one end of the cable are transferred to
      the user via a sliding mechanism at the end-effector located at the other end of
      the cable. The end-effector provides the range of movement up to 12 cm. The force
      is controlled by an open-loop impedance algorithm and can become up to 15 N.

PMID- 16404093
TI  - A hip surgery simulator based on patient specific models generated by automatic
      segmentation.
AB  - The use of surgical simulator systems for education and preoperative planning is
      likely to increase in the future. A natural course of development of these
      systems is to incorporate patient specific anatomical models. This step requires
      some kind of segmentation process in which the different anatomical parts are
      extracted. Anatomical datasets are, however, usually very large and manual
      processing would be too demanding. Hence, automatic, or semi-automatic, methods
      to handle this step are required. The framework presented in this paper uses
      nonrigid registration, based on the morphon method, to automatically segment the
      hip anatomy and generate models for a hip surgery simulator system.

PMID- 16404094
TI  - Semi-automatic segmentation and tracking of CVH data.
AB  - Construction of speed function is crucial in applying level set method for
      medical image segmentation. We present a unified approach for segmenting and
      tracking of the high-resolution Chinese Visible Human (CVH) data. The underlying
      link of these two parts relies on the proposed variational framework for the
      speed function. Our proposed method can be applied to segmenting the first slice
      of the volume data, in the first step; It can also be adapted to track the
      boundaries of the homogeneous organs in the following serial images. In addition
      to promising segmentation results, the tracking procedure shows the advantage of
      less amount of user intervention.

PMID- 16404095
TI  - Tissue engineering templates using minimal surfaces.
AB  - The status quo of tissue engineering can be summarized as "a random walk through
      the design space". The existing scaffold designs based on computeraided design
      (CAD) and solid freeform fabrication (SFF) are anti-biomorphic and mechanically
      weak cubic partitions with sharp edges. We introduce minimal surface based unit
      cells to create biomorphic scaffolds with optimal stress/strain distribution and
      superior mechanical strength.

PMID- 16404096
TI  - Rendering of virtual fixtures for MIS using generalized sigmoid functions.
AB  - To avoid undesired collisions and improve the level of safety and precision,
      artificial potential field (APF) can be employed to generate virtual forces
      around protected tissue and to provide surgeons with real-time force refection
      through haptic feedback. In this paper, we propose a potential field-based force
      model using the generalized sigmoid function, and show that it can represent a
      large class of shapes. The proposed approach has several advantages such as
      computational efficiency, easily adjustable level of force reflection, and force
      continuity.

PMID- 16404097
TI  - Mobile in vivo biopsy and camera robot.
AB  - A mobile in vivo biopsy robot has been developed to perform a biopsy from within
      the abdominal cavity while being remotely controlled. This robot provides a
      platform for effectively sampling tissue. The robot has been used in vivo in a
      porcine model to biopsy portions of the liver and mucosa layer of the bowel.
      After reaching the specified location, the grasper was actuated to biopsy the
      tissue of interest. The biopsy specimens were gathered from the grasper after
      robot retraction from the abdominal cavity. This paper outlines the steps towards
      the successful design of an in vivo biopsy robot. The clamping forces required
      for successful biopsy are presented and in vivo performance of this robot is
      addressed.

PMID- 16404098
TI  - An integrated system for real-time image guided cardiac catheter ablation.
AB  - Minimally invasive cardiac catheter ablation procedures require effective
      visualization of the relevant heart anatomy and electrophysiology (EP). In a
      typical ablation procedure, the visualization tools available to the cardiologist
      include bi-plane fluoroscopy, real-time ultrasound, and a coarse 3D model which
      gives a rough representation of cardiac anatomy and electrical activity.
      Recently, there has been increased interest in incorporating detailed, patient
      specific anatomical data into the cardiac ablation procedure. We are currently
      developing a prototype system which both integrates a patient specific,
      preoperative data model into the procedure as well as fuses the various
      visualization modalities (i.e. fluoroscopy, ultrasound, EP) into a single
      display. In this paper, we focus on two aspects of the prototype system. First,
      we describe the framework for integrating the various system components,
      including an efficient communication protocol. Second, using a simple two-chamber
      phantom of the heart, we demonstrate the ability to integrate preoperative data
      into the ablation procedure. This involves the registration and visualization of
      tracked catheter points within the cardiac chambers of the preoperative model.

PMID- 16404099
TI  - Stress management using UMTS cellular phones: a controlled trial.
AB  - One of the best strategies for dealing with stress is learning how to relax.
      However, relaxing is difficult to achieve in typical real world situations. For
      this study, we developed a specific protocol based on mobile narratives -
      multimedia narratives experienced on UMTS/3G phones - to help workers in reducing
      commuting stress. In a controlled trial 33 commuters were randomly divided
      between three conditions: Mobile narratives (MN); New age music and videos (NA);
      no treatment (CT). In two consecutive days the MN and NA samples experienced
      during their commute trip 2 x 2 6-minute multimedia experiences on a Motorola
      A925 3G phone provided by the "TRE" Italian UMTS carrier: the MN sample
      experienced a mobile narrative based on the exploration of a desert beach; the NA
      sample experienced a commercial new age video with similar visual contents. The
      trials showed the efficacy of mobile narratives in reducing the level of stress
      experienced during a commute trip. No effects were found in the other groups.
      These results suggest that 3G mobile handsets may be used as relaxation tool if
      backed by a specific therapeutic protocol and meaningful narratives.

PMID- 16404100
TI  - Structure-function relationships in the human visual system using DTI, fMRI and
      visual field testing: pre- and post-operative assessments in patients with
      anterior visual pathway compression.
AB  - The focus of this project is to improve our understanding of the relationships
      between brain structure and function in patients presenting with anterior visual
      pathway compression using functional MRI (fMRI), visual field(VF) maps and
      diffusion tensor imaging (DTI). Significant visual loss can occur when large
      pituitary lesions compress the optic chiasm. Surgical resection of these lesions
      decompresses the chiasm and can lead to visual recovery. In this preliminary
      study, we selected patients presenting with slowly progressive visual loss
      secondary to a compressive pituitary region mass. Using preoperative DTI data, we
      reconstructed white matter projections of the optic radiations and demonstrated a
      structural correlation with functional vision as quantified by formal visual
      field mapping and fMRI. The structural data generated through a fiber tracking
      algorithm may represent a potentially powerful tool to better understand
      functional visual deficits in patients with anterior visual pathway compression.
      Furthermore, we believe that specific patterns in preoperative DTI data may
      predict the likelihood of postoperative visual recovery in a select group of
      patients.

PMID- 16404101
TI  - Estimation of skeletal movement of human locomotion from body surface shapes
      using dynamic spatial video camera (DSVC) and 4D human model.
AB  - We have been developing a DSVC (Dynamic Spatial Video Camera) system to measure
      and observe human locomotion quantitatively and freely. A 4D (four-dimensional)
      human model with detailed skeletal structure, joint, muscle, and motor
      functionality has been built. The purpose of our research was to estimate
      skeletal movements from body surface shapes using DSVC and the 4D human model.
      For this purpose, we constructed a body surface model of a subject and resized
      the standard 4D human model to match with geometrical features of the subject's
      body surface model. Software that integrates the DSVC system and the 4D human
      model, and allows dynamic skeletal state analysis from body surface movement data
      was also developed. We practically applied the developed system in dynamic
      skeletal state analysis of a lower limb in motion and were able to visualize the
      motion using geometrically resized standard 4D human model.

PMID- 16404102
TI  - Validation of open-surgery VR trainer.
AB  - VREST (Virtual Reality Educational Surgical Tools) is developing a universal and
      autonomous simulation platform which can be used for training and assessment of
      medical students and for continuing education of physicians. With the VREST -
      Virtual Lichtenstein Trainer, simulating the open surgery procedure of the
      inguinal hernia repair according to Lichtenstein, the validation of the simulator
      is ongoing. Part of this trajectory is the evaluation of the transfer of training
      of the virtual incision making. One group of students trained incision making on
      the VREST platform where the control group did not. In an experiment both groups
      has to perform several incision tasks on a manikin. The results are not available
      yet but will be presented at the MMVR14 conference.

PMID- 16404103
TI  - Open surgery in VR: inguinal hernia repair according to Lichtenstein.
AB  - VREST (Virtual Reality Educational Surgical Tools) is developing a universal and
      autonomous simulation platform which can be used for training and assessment of
      medical students and for continuing education of physicians. A workstation
      consisting of two haptic devices and a 3D vision system is part of the VREST
      platform. Another part of the platform is a generic software environment in which
      lessons can be built by the teacher and performed by their students. Using the
      platform one can see, feel and decide as in reality. With the assessment tool the
      progress and skills of the students can be supervised. The first lesson build on
      the VREST platform is an inguinal hernia repair according to Lichtenstein. This
      is an open surgery procedure. The VREST platform is used prior to the first
      operating room surgery of the resident. Interactive models and case dependent
      feedback is used to enlarge the residents' cognition. This should reduce the
      training time in the operating room.

PMID- 16404104
TI  - Pneumothorax influenced 3D lung deformations.
AB  - In this paper we propose a method to simulate morphological changes caused by
      both closed and tension pneumothorax. We consider a clinical parameter, the
      pneumothorax-index (i.e., the degree of lung collapse), as the input to the
      simulation. Specifically, such an index constitutes a key parameter to the
      computation of the changes in size and shape of the affected lung. Once the index
      is obtained, the increase in ventilation rate and the change in the pressure
      volume relationship of the affected lung are then computed. For tension
      pneumothorax, the air continuously flows into the pleural cavity and thus every
      exhalation is followed by the changes seen for a closed pneumothorax, until the
      affected lung collapses. The subsequent closure of pulmonary veins and resulting
      hyper expansion of the apposing lung is also presented. Results show a real-time
      visualization of closed and tension pneumothorax using a high-resolution 3D model
      obtained from a normal human subject.

PMID- 16404105
TI  - Documentation and teaching of surgery with an eye movement driven head-mounted
      camera: see what the surgeon sees and does.
AB  - A first proof of concept was developed for a head-mounted video camera system
      that is continuously aligned with the user's orientation of gaze. In doing so, it
      records images from the user's perspective that can document manual tasks during,
      e.g., surgery. Eye movements are tracked by video-oculography and used as signals
      to drive servo motors that rotate the camera. Thus, the sensorimotor output of a
      biological system for the control of eye movements evolved over millions of years
      is used to move an artificial eye. All the capabilities of multi-sensory
      processing for eye, head, and surround motions are detected by the vestibular,
      visual, and somatosensory systems and used to drive a technical camera system. A
      camera guided in this way mimics the natural exploration of a visual scene and
      acquires video sequences from the perspective of a mobile user, while the
      oculomotor reflexes naturally stabilize the camera on target during head and
      target movements. Various documentation and teaching applications in health care,
      industry, and research are conceivable.

PMID- 16404106
TI  - A simulation-based training system for surgical wound debridement.
AB  - A simulation-based training system for surgical wound debridement was developed
      and comprises a multimedia introduction, a surgical simulator (tutorial
      component), and an assessment component. The simulator includes two PCs, a haptic
      device, and mirrored display. Debridement is performed on a virtual leg model
      with a shallow laceration wound superimposed. Trainees are instructed to remove
      debris with forceps, scrub with a brush, and rinse with saline solution to
      maintain sterility. Research and development issues currently under investigation
      include tissue deformation models using mass-spring system and finite element
      methods; tissue cutting using a high-resolution volumetric mesh and dynamic
      topology; and accurate collision detection, cutting, and soft-body haptic
      rendering for two devices within the same haptic space.

PMID- 16404107
TI  - Achieving proper exposure in surgical simulation.
AB  - One important technique common throughout surgery is achieving proper exposure of
      critical anatomic structures so that their shapes, which may vary somewhat among
      patients, can be confidently established and avoided. In this paper, we present
      an algorithm for determining which regions of selected structures are properly
      exposed in the context of a mastoidectomy simulation. Furthermore, our algorithm
      then finds and displays all other points along the surface of the structure that
      lie along a sufficiently short and straight path from an exposed portion such
      that their locations can be safely inferred. Finally, we present an algorithm for
      providing realistic visual cues about underlying structures with view-dependent
      shading of the bone.

PMID- 16404108
TI  - Structural flexibility of laparoscopic instruments: implication for the design of
      virtual reality simulators.
AB  - Laparoscopic training, under simulated settings, benefits from high fidelity
      models of the actual environment. This study was aimed at reducing uncertainty in
      the displacement and loads experienced by a laparoscopic instrument during
      surgical training. Infrared tracking of laparoscopic instruments is ineffective
      when real tissues attenuate the infrared signals. Incorporating the use of strain
      gauges for tip deflection measurements allows for online motion and load tracking
      during a procedure. Strain gauge voltages and infrared markers indicating
      displacement were both linear with respect to loads up to 700 grams. The
      resultant strain gauge voltage was equated to deflection values with a
      calibration constant. The results serve two purposes. First, it may enable the
      tracking and analysis of the skill level of novice surgeons using bench models.
      Second, the mechanical model of each instrument can be quantified and
      incorporated into virtual simulations, thus increasing model fidelity,
      effectively leading to better learning.

PMID- 16404109
TI  - Selective tessellation algorithm for modeling interactions between surgical
      instruments and tissues.
AB  - We present a selective spatial tessellation algorithm that is specifically
      optimized for instrument-to-tissue and instrument-to-instrument collision
      detection cases, which are the essential part of interaction modeling in surgery
      simulation with haptic feedback. Virtual surgeries demand haptic rate collision
      solutions only when instruments are involved in collisions. Other collision cases
      can be processed at slower rates. The proposed selective tessellation algorithm
      is capable of differentiating among various collision cases and assigning
      different priorities to their processing. Without making assumptions about any
      object movement, the algorithm derives clipping volume as collision detection
      regions which tightly enclose the objects of interest. Results of implementation
      of the algorithm in a surgical simulation are provided.

PMID- 16404110
TI  - Realistic irrigation visualization in a surgical wound debridement simulator.
AB  - Wound debridement refers to the removal of necrotic, devitalized, or contaminated
      tissue and/or foreign material to promote wound healing. Surgical debridement
      uses sharp instruments to cut dead tissue from a wound and it is the quickest and
      most efficient method of debridement. A wound debridement simulator can ensure
      that a medical trainee is competent prior to performing a procedure on a genuine
      patient. Irrigation is performed at different stages of debridement in order to
      remove debris and reduce the bacteria count through rinsing the wound. This paper
      presents a novel approach for realistic irrigation visualization based on texture
      representations of debris. This approach applies image processing techniques to a
      series of images, which model the cleanliness of the wound. The active texture is
      generated and updated dynamically based on the irrigation state, location, and
      range. Presented results demonstrate that texture mapping and image processing
      techniques can provide effective and efficient solutions for irrigation
      visualization in the wound debridement simulator.

PMID- 16404111
TI  - Simulating bending behaviour of thread and needle.
AB  - The traditional approach to modeling bending of a thread consists in adding
      springs connecting non-neighbouring keypoints. An alternative is introduced,
      starting by articulating an intrinsic bending energy of an arbitrary joint, and
      deducing the resultant justification forces. Significant visual appeal is thus
      gained, with negligible computational costs. We further investigate the bending
      interaction of a spline with a connected rigid body, and mention several
      generalization directions.

PMID- 16404112
TI  - Web-based viewer for systematic combination of anatomy and nomenclature.
AB  - Integrating anatomic nomenclature with geometric anatomic data via a web
      interface and providing illustration and visualization tools presents numerous
      challenges. We have developed a library of anatomic models and methods for
      navigating anatomic nomenclature. Based on the library and tools, we have
      developed a simple, yet powerful, open web-based tool that uses tree navigation
      and selection for assembling and downloading self-documenting anatomic scenes in
      Virtual Reality Modeling Language.

PMID- 16404113
TI  - Haptic feedback for the GPU-based surgical simulator.
AB  - The GPU has proven to be a powerful processor to compute spring-mass based
      surgical simulations. It has not previously been shown however, how to
      effectively implement haptic interaction with a simulation running entirely on
      the GPU. This paper describes a method to calculate haptic feedback with limited
      performance cost. It allows easy balancing of the GPU workload between
      calculations of simulation, visualisation, and the haptic feedback.

PMID- 16404114
TI  - Avionics-compatible video facial cognizer for detection of pilot incapacitation.
AB  - High-acceleration loss of consciousness is a serious problem for military pilots.
      In this laboratory, a video cognizer has been developed that in real time detects
      facial changes closely coupled to the onset of loss of consciousness. Efficient
      algorithms are compatible with video digital signal processing hardware and are
      thus configurable on an autonomous single board that generates alarm triggers to
      activate autopilot, and is avionics-compatible.

PMID- 16404115
TI  - TRUS-fluoroscopy fusion for intraoperative prostate brachytherapy dosimetry.
AB  - A fluoroscopic to TRUS fusion based approach for intraoperative prostate
      brachytherapy dosimetry was developed. Seed images were identified from multiple
      fluoroscopic images and reconstructed to determine the three dimensional
      distribution of the implanted seeds. Seeds identified from the TRUS images were
      used as fiducials for the registration between fluoroscopic and TRUS images. Dose
      analysis was then performed based on the fused images. A phantom study was
      performed to test this approach and a 3 mm registration error was observed.
      Radiation isodose contours were generated and superimposed on the TRUS images.

PMID- 16404116
TI  - Augmented reality with fibre optics.
AB  - In this paper we present the concept and the first results of the Fibre Optic
      Pointer - a miniaturized Augmented Reality system for craniofacial surgery. The
      objective is the integration into surgical instruments.

PMID- 16404117
TI  - Bubble packing application in computerized planning of cryosurgery.
AB  - Among many factors, the effectiveness of the cryoprocedure is determined by the
      quality of the cryoprobes layout. A computerized planning tool for optimizing
      this layout has the potential of improving the outcome of cryosurgery, reducing
      post-operative complications, and reducing the cost of the clinical operation. As
      part of an ongoing effort to develop planning tools for cryosurgery, the current
      study takes a novel approach, based on bubble-packing method. This study shows
      that the application of bubble-packing shortens runtime by an order of magnitude.
      In this study, the bubble-packing method is integrated with bioheat transfer
      simulations to demonstrate the quality of planning.

PMID- 16404118
TI  - Tracking endoscopic instruments without localizer: image analysis-based approach.
AB  - In this paper we present an approach to localize endoscopic instruments with
      respect to the camera position, purely based on video image processing. No
      localizers are required. The only requirement is a coloured strip at the distal
      part of the instrument shaft, to facilitate image segmentation. The method
      exploits perspective image analysis applied to the cylindrical shape of the
      instrument shaft, allowing to measure five degrees of freedom of the instrument
      position and orientation. We describe the method theoretically and experimentally
      derive calibration curves for tuning the parameters of the algorithm. Results
      show that the method can be used for applications where accuracy is not critical,
      e.g. workspace analysis, gesture analysis, augmented-reality guidance,
      telementoring, etc. If this method is used in combination with a robotic camera
      holder, full localization with respect to the operating room can be achieved.

PMID- 16404119
TI  - Computer-aided forensics: facial reconstruction.
AB  - The 3D reconstruction of facial features from skeletal remains is a key component
      to the identification of missing persons and victims of violent crime. A
      comprehensive Computed Tomography (CT) head-scan database is currently being
      collected which will enable a new approach to forensic facial reconstruction.
      Using this unique resource, we show how a face space can be tailored to a
      specific unknown, or questioned skull. A set of database derived estimates of the
      questioned face is constructed by first computing non-rigid transformations
      between the known head-scan skulls and the questioned skull followed by
      application of these transformations to the known head-scan faces. This
      effectively factors out influences due to skeletal variation. A tailored face
      space is formed by applying Principal Component Analysis (PCA) to this ensemble
      of estimates of the questioned face. Thus, the face space is a direct
      approximation of correlated soft tissue variance indicative of the population.
      Ours is the first mathematical representation of the face continuum associated
      with a given skull. Embedded in this space resides the elements needed for
      recognition.

PMID- 16404120
TI  - Registration and segmentation for the high resolution visible human male images.
AB  - The Visible Human project by National Library of Medicine (NLM) resulted in two
      sets of cryosection images of a human male (VHM): low (LR) and high (HR)
      resolution. By leveraging the already registered and segmented LR images, we have
      successfully achieved the same for the entire HR image set. 3D models of human
      anatomical structures generated using this HR image set, presented in this paper,
      provide qualitative demonstration of the high accuracy of the HR registration and
      segmentation.

PMID- 16404121
TI  - Flatland sound services design supports virtual medical training simulations.
AB  - This paper describes the evolution of the design of Flatland Sound Service (FSS),
      a sound system for virtual reality required to support Project TOUCH (Telehealth
      Outreach for Unified Community Health), a multi-year collaboration between the
      Schools of Medicine at the state Universities of Hawaii and of New Mexico. Two
      virtual sonic environments specific case scenarios, a neurological trauma (Toma)
      and a virtual kidney nephron (Nephron), were developed using integrated services
      provided by FSS. Flatland is an open source visualization and virtual reality
      application development tool created at the University of New Mexico.

PMID- 16404122
TI  - Simulating tele-manipulator controlled tool-tissue interactions using a nonlinear
      FEM deformable model.
AB  - Enhanced visualization of an operating scene presented by a robotically assisted
      tele-manipulator system such as the da Vinci(TM) can be provided through the use
      of augmented reality facilities. Generating overlays from 3D models and the intra
      operative video allows the surgeon to acquire greater information about the
      surgical scene. Tool-tissue interactions must be tracked to ensure the overlays
      are updated regularly and accurately. The work presented here describes how these
      interactions may be modelled by integrating a nonlinear finite element model with
      the 3D reconstruction and using the tool kinematic data as input to the
      deformation.

PMID- 16404123
TI  - Physically accurate mesh simulation in a laparoscopic hernia surgery simulator.
AB  - In this paper we use the 2D angular spring based mass-spring-damper (AMSD) model
      to simulate the plastic mesh in a laparoscopic hernia surgery simulator. We
      propose a physically based method to systematically derive the optimal parameters
      of the 2D AMSD model. While the traditional 2D MSD model lacks resistance against
      bending, the 2D AMSD model with optimized parameters can provide correct bending
      resistance as well as stretching resistance. The simulated mesh is demonstrated
      to be much more realistic.

PMID- 16404124
TI  - 3D surface accuracy of CAD generated skull defect contour.
AB  - The creation of a satisfactory cosmetic outcome in the repair of cranial defects
      relies on manual skill. However, computer aided design is gaining acceptance in
      the creation of custom cranial implants. The purpose of this work is to
      demonstrate the accuracy of a CAD generated skull defect contours using 3D
      difference maps. 3D multi-slice CT scanning was carried out on a life size
      plastic skull. Surface models were generated of the original skull and of
      temporofrontal and parietal defects. Surface contours were interpolated towards
      the centre of the defect from the edges where it was blended. The CAD contour
      deviation ranged from 0.0 mm to 2.0 mm with 80% of the total defect area less
      than 0.66 mm as measured by difference maps. CAD techniques can be used to
      produce contours for the repair of cranial defects with minimum deviation from
      the original skull contour. This enables accurate design and production of
      cranial implants.

PMID- 16404125
TI  - "Virtual unwrapping" of a mummified hand.
AB  - The purpose of this work is to demonstrate the feasibility of medical virtual
      reality technologies in the investigation of a mummified hand. The Ulster Museum
      obtained the mummy hand, which originated from Thebes, without any identifying
      information. The mummified hand was investigated using conventional X-ray and 3D
      multi-slice Computed Tomography (CT). Imaging revealed a range of fractures of
      the wrist, metacarpals and phalanges whilst 3D CT demonstrated internal
      structures using volume rendering. The absence of any features of bone healing at
      the fracture sites would imply that they occurred just prior to death or in the
      mummified state possibly during excavation. Conventional X-ray imaging indicated
      that the hand, although small, was likely to have originated from an adult.
      Medical imaging and virtual reality display will enable us to produce a rapid
      prototyped model using fused deposition technology. Therefore, further
      paleopathological research can be performed on the replica without the need to
      handle the original specimen.

PMID- 16404126
TI  - A haptics based simulator for laparoscopic pyeloplasty.
AB  - We present a methodology for modeling the surgical procedures involved in
      robotics-assisted Pyeloplasty, which is a minimally invasive surgical procedure
      for correcting a kidney ureteropelvic junction obstruction. The simulator
      facilitates surgical training of laparoscopic pyeloplasty by providing both
      visual and haptic feedback to the trainee.

PMID- 16404127
TI  - Effects of assembling virtual fixtures on learning a navigation task.
AB  - An approach to enhance navigation task performance is to integrate sensory
      guidance (virtual fixtures) into a virtual training system. To evaluate the
      effects of adding virtual fixtures to skill acquisition, 32 subjects were
      required to use a PHANToM input device, to transport a virtual object through a
      computer generated 3-D graphic maze. Subjects practiced navigation under 4
      conditions: the maze was augmented with either a graphic fixture (G), attractive
      force field (F), both graphic and force field (GF), or no (N) virtual fixture.
      Fifteen practice trials were given before subjects were transferred to a
      situation with no virtual fixtures. Results showed that the implementation of the
      force field assisted task performance during practice; however, it failed to show
      positive transfer effects. In contrast, adding a graphic fixture to the virtual
      maze helped subjects to define the optimal pathway throughout navigation, which
      facilitated skill acquisition.

PMID- 16404128
TI  - Zero-dose fluoroscopy-based close reduction and osteosynthesis of diaphyseal
      fracture of femurs.
AB  - This paper presents a novel technique to create a computerized fluoroscopy with
      zero-dose image updates for computer-assisted fluoroscopy-based close reduction
      and osteosynthesis of diaphyseal fracture of femurs. With the novel technique,
      repositioning of bone fragments during close fracture reduction will lead to
      image updates in each acquired imaging plane, which is equivalent to using
      several fluoroscopes simultaneously from different directions but without any X
      ray radiation. Its application facilitates the whole fracture reduction and
      osteosynthesis procedure when combining with the existing leg length and
      antetorsion restoration methods and may result in great reduction of the X-ray
      radiation to the patient and to the surgical team. In this paper, we present the
      approach for achieving such a technique and the experimental results with plastic
      bones.

PMID- 16404129
TI  - Acute hypokalemia may not be an effective way to sensitize the in situ canine
      heart for sparfloxacin-induced long QT syndrome.
AB  - Extents of the sparfloxacin (3 - 10 mg/kg, i.v.)-induced QT interval prolongation
      under normokalemic and hypokalemic conditions were assessed in halothane
      anesthetized beagle dogs (n = 5). The hypokalemic condition was induced by an
      oral administration of furosemide (200 mg/kg per day) for 3 days, which decreased
      the serum potassium concentration from 3.65 +/- 0.13 to 2.35 +/- 0.13 mM (P <
      0.05). However, the decrease of potassium concentration by itself did not affect
      the extent of the sparfloxacin-induced QT interval prolongation. These results
      indicate that acute hypokalemia may not severely sensitize the in situ heart for
      drug-induced long QT syndrome as previously thought.

PMID- 16404130
TI  - Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in
      mice via LPA receptors.
AB  - Lysophosphatidic acid (LPA), the simplest of the water-soluble phospholipids, can
      evoke various biological responses. The present study examined the activity of
      LPA to induce plasma exudation and histamine release in mice. Plasma exudation
      was assessed by extravasation of Evans blue. Subcutaneous administration of LPA
      (1 - 100 microg/site) led to increased plasma exudation in the skin. The LPA
      induced plasma exudation was inhibited by ketotifen, a histamine H1-receptor
      antagonist, and diacylglycerol pyrophosphate (DGPP), a LPA1/LPA3-receptor
      antagonist. Moreover, pretreatment with pertussis toxin and DGPP inhibited the
      histamine release from peritoneal mast cells induced by LPA. These findings
      indicate that plasma exudation induced by LPA is mediated by histamine release
      from mast cells via LPA receptor(s), presumably LPA1 and/or LPA3, coupled to
      G(i/o) proteins. Moreover, these findings point to a role of LPA in the
      pathomechanisms of various allergic disorders.

PMID- 16404131
TI  - Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on
      peroxisome proliferator response element pathway.
AB  - To investigate the possibility that natural medicines affect lipid metabolism by
      regulating lipoprotein lipase (LPL) expression, a green fluorescent protein (GFP)
      gene was constructed downstream of the peroxisome proliferator response element
      (PPRE) and the constructed plasmid was microinjected into Xenopus oocytes to
      establish a PPRE regulatory reporter system. Using this system, hawthorn
      flavonoids were quickly selected from a panel of natural medicines and found to
      up-regulate GFP expression by an effect on PPRE. To confirm the effect of
      hawthorn flavonoids, we treated mice orally with water (control), hawthorn
      flavonoids, and pioglitazone and measured the LPL levels in serum, adipose
      tissue, and muscle by an enzyme-linked immunosorbent assay. The serum LPL levels
      were no different from the controls after treatment with either hawthorn
      flavonoids or pioglitazone, but LPL increased significantly in muscular tissues
      and decreased in adipose tissues. These results demonstrate that hawthorn
      flavonoids meditate LPL expression in mice with tissue-specific differences. A
      novel PPRE regulatory report system was established for rapid and effective
      selection and evaluation of LPL-mediating drugs.

PMID- 16404132
TI  - Anti-arthritic effects of Ephedra sinica STAPF herb-acupuncture: inhibition of
      lipopolysaccharide-induced inflammation and adjuvant-induced polyarthritis.
AB  - Anti-inflammatory and anti-arthritic effects of water distillates of Ephedra
      sinica STAPF (ES), in herb-acupuncture, on the inflammatory responses of
      arthritis was investigated using phorbol 12-myristate 13-acetate
      (PMA)/lipopolysaccharide (LPS)-induced human macrophage and adjuvant-induced
      arthritic rat. The luciferase reporter vectors driven by the tumor necrosis
      factor (TNF)-alpha and cyclooxygenase-2 promoters were transiently transfected
      into U937 cells, which were then differentiated and stimulated by PMA and LPS,
      respectively, to develop an in vitro anti-inflammation assay system. The
      luciferase activities, observed in the activated U937 cells, were significantly
      inhibited by ES herb-acupuncture, compared to those of PD98509 and berberine. To
      evaluate ES herb-acupuncture as a novel anti-arthritic therapy, a polyarthritic
      rat model was developed using heat-killed Mycobacterium tuberculosis, and 50 mul
      of ES distillate was subcutaneously injected into the ST36 acupoint on each knee
      joint. While the articular indexes of arthritic rats were evidently decreased by
      ES herb-acupuncture, their body weights did not regain their initial levels. This
      may be due to the accelerating effects of ES on weight-loss and fat consumption.
      The mRNA expressions of TNF-alpha and interleukin (IL)-6 genes, which were
      closely stimulated in the arthritic rat joints, were found to be restored to the
      normal levels through the ES treatment. In the case of IL-1beta, the recovery was
      not significant but substantial. The anti-arthritic effect of ES herb-acupuncture
      was not found in the ES-treated/non-acupoint group. In conclusion, the ES herb
      acupuncture into the ST36 acupoint was found to be effective in alleviating the
      inflammatory response and thus arthritic symptoms in adjuvant-induced arthritic
      rats.

PMID- 16404133
TI  - Analysis of vasoreactivity of isolated human radial artery.
AB  - Radial artery (RA) is increasingly used as graft for coronary artery bypass
      grafting due to its good long-term patency. However, the mechanism of peri- and
      post-operative spasm is still unclear. Because of that, the aim of our study is
      to analyze the contractility of RA and to determine whether the presence of
      functional endothelium alters its contractile properties. Contractions of
      isolated RA rings were provoked by exogenously applied vasoconstrictors or by
      electrical field stimulation (EFS, 20 Hz). The order of vasoconstrictors potency
      based on their EC50 values was as follows: angiotensin II > phenylephrine > 5
      hydroxytriptamine. Presence of endothelium increased both EC50 and maximal
      contraction to phenylephrine and angiotensin II, but inhibited reactivity of RA
      to 5-hydroxytriptamine. Spontaneous rhythmic contractions (SRC, <4 mHz) and EFS
      induced contractions of RA are endothelium-independent and weaker than
      contractions induced by exogenously applied vasoconstrictors. Our study concludes
      that RA shows marked sensitivity and reactivity to angiotensin II, phenylephrine,
      and 5-hydroxytriptamine. Further investigations are necessary to answer why
      angiotensin II and phenylepehrine induce stronger contractions in the presence of
      endothelium. In addition, SRC as well as contractions of neurogenic origin may
      take part in developing vascular spasm of RA.

PMID- 16404134
TI  - Molecular mechanisms and therapeutic strategies of chronic renal injury:
      physiological role of angiotensin II-induced oxidative stress in renal medulla.
AB  - Renal medullary circulation has now been found to play a fundamental role in
      regulating long-term blood pressure control and fluid balance. Elevation of
      superoxide or reduction of nitric oxide (NO) in renal medulla decreases medullary
      blood flow and Na excretion, resulting in sustained hypertension. Angiotensin II
      (Ang II)-induced interaction of superoxide and NO was determined in thin tissue
      strips isolated from the renal outer medullary region of Sprague-Dawley rats
      using fluorescent microscopy techniques. Ang II can induce diffusion of NO, but
      not superoxide, from the medullary thick ascending limb (mTAL) to the surrounded
      vasa recta. However, when NO is reduced by the NO scavenger carboxy-PTIO, Ang II
      can induce superoxide diffusion from mTAL to vasa recta pericytes. Therefore, the
      physiological action of oxidative stress in renal medullary region is
      demonstrated as balance of superoxide and NO diffusion ("tubulo-vascular cross
      talk"). These results explain how chronically hypoxic medulla can maintain blood
      flow. In other studies using chronically instrumented rats, we found that nearly
      70% of Ang II-induced medullary renal injury was dependent on pressure determined
      by servo-control of renal perfusion pressure, whereas 30% of the injury was non
      hemodynamic. We conclude that oxidative stress within the renal medulla can
      induce hypertension and also make the kidney functionally more vulnerable to the
      effects of Ang II.

PMID- 16404135
TI  - Effects of methanol extracts of Caesalpinia bonducella and Bauhinia racemosa on
      hematology and hepatorenal function in mice.
AB  - The aim of the present investigation deals with the hematology and hepatorenal
      function of Caesalpinia bonducella Flem. and Bauhinia racemosa Lam. belonging to
      the Family: Caesalpiniaceae, and used in the traditional system of medicine. The
      tribal people of Kolli Hills, Tamil Nadu, India, use the leaves of Caesalpinia
      bonducella and the stem bark of Bauhinia racemosa in combination with some other
      herbs for the treatment of various tumors, liver disorders, inflammation and some
      other diseases. In ancient Ayurveda medicine these plants were mentioned to
      possess antitumor agents. Since there are no scientific reports regarding the
      toxicological aspects of these plants, the present investigation deals with the
      sub-chronic toxicity studies of a methanol extract of Caesalpinia bonducella
      (MECB) leaves and Bauhinia racemosa (MEBR) stem bark in Swiss albino mice. The
      MECB and MEBR were administered intraperitoneally (i.p) to Swiss albino mice
      twice a week for thirteen weeks. No significant alterations in hematological,
      biochemical and histopathological parameters were observed in the MECB- and MEBR
      treated groups at the doses of 100 and 200 mg/kg body weight. Administration of
      MECB and MEBR at the dose of 400 mg/kg body weight elevated the levels of serum
      enzymes and altered the hematological parameters. Our results suggested that MECB
      and MEBR at doses 100 and 200 mg/kg body weight did not induce any toxic effects
      in the mice. Adverse effect was noted at the dose of 400 mg/kg body weight.

PMID- 16404136
TI  - Acute, subchronic and chronic toxicity studies of a synthetic antioxidant, 2,2'
      isobutylidenebis(4,6-dimethylphenol) in rats.
AB  - General toxicity studies on 2,2'-isobutylidenebis(4,6-dimethylphenol)(IBBMP) were
      conducted using male and female Wistar rats. In the acute test, the oral LD50
      values were 119 mg/kg BW in males and 103 mg/kg BW in females. Hypersensitivity,
      loss of righting reflex and abdominal position were observed. In the subchronic
      test, rats were fed a diet containing IBBMP at levels of 0, 20, 100 or 500 ppm
      for 13 weeks with interim sacrifice at 4 weeks (equal to 0, 1.1, 5.5 or 27.9
      mg/kg BW/day in males and 0, 1.1, 5.9 or 29.6 mg/kg BW/day in females). In both
      sexes, there were no changes in general condition, body weight gains and food
      intakes in all groups. No deaths were observed in all groups. Significant
      increase in AST was observed in 500 ppm males at Week 4. However, the change was
      not observed at Week 13. Slight but significant decreases in creatinine were also
      observed in 100 ppm females at Week 13 and 500 ppm males and females at Weeks 4
      and 13. Total cholesterol (T-CHO) was significantly elevated in females of the
      500 ppm group at Weeks 4 and 13. Absolute and relative liver weights were
      increased in 500 ppm of both sexes at Week 4. In females, the increases were also
      observed at Week 13. However, no remarkable histopathological findings were
      observed in all treated groups. In the chronic test, rats were fed a diet
      containing IBBMP at levels of 0, 100, 500 and 1500 ppm for 18 months with interim
      sacrifices at 6 and 12 months (equal to 0, 3.8, 19.4 or 59.4 mg/kg BW/day in
      males and 0, 4.3, 20.9 or 67.5 mg/kg BW/day in females). No remarkable changes in
      general appearance were observed in any rats. Body weight gains, food intakes and
      survival rates in all treated animals were comparable to those of the control. No
      remarkable changes in the hematological parameters were observed. T-CHO was
      significantly elevated in females of the 1500 ppm groups throughout the
      experiment. Significant increases or tendencies for increase in relative liver
      weights were observed in the 500 and 1500 ppm animals of both sexes. Increased
      incidences of swelling in liver cells were observed in 1500 ppm males at 6 months
      and 1500 ppm females at 12 and 18 months. At 18 months, dose-dependent increases
      in thickness of basement membrane of renal tubules and Bowman's capsule and cell
      infiltration to the interstitium of the kidney were observed in males.
      Significant increases of hyaline cast and basophilic change were also observed in
      1500 ppm males. In females, increased incidences of hyaline cast were observed at
      500 ppm and higher at 18 months. No other toxicity was apparent. No neoplastic
      lesions that could be attributed to IBBMP were observed in any organs of either
      sex. From the result of the chronic toxicity test, the no-observed-adverse-effect
      level (NOAEL) for IBBMP was concluded to be 100 ppm in the diet (4.26 mg/kg
      BW/day) in female rats on the basis of induction of hyaline cast in renal tubules
      at 500 ppm, whereas, in males, only a lowest-observed-adverse-effect level
      (LOAEL) was given as 100 ppm (3.84 mg/kg BW/day) on the basis of induction of
      thickening of basement membrane in renal tubules at 100 ppm.

PMID- 16404138
TI  - A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone
      destruction in experimental periodontitis in rats.
AB  - An acidic microenvironment formed by vacuolar ATPase (V-ATPase) expressed in
      plasma membranes of osteoclasts is thought to be indispensable for bone
      resorption. This study examined the efficacy of a novel V-ATPase inhibitor,
      FR202126, in reducing alveolar bone loss caused by experimental periodontitis in
      rats. FR202126 inhibited H+ transport in plasma membrane vesicles of murine
      osteoclasts, whereas FR202126 exerted no effect on H+ transport of mitochondrial
      ATPase or gastric H+,K+-ATPase, indicating that FR202126 is a specific inhibitor
      of V-ATPase. As expected from the mechanism, FR202126 remarkably inhibited in
      vitro bone resorption whatever bone resorptive factors were added. Moreover,
      FR202126 was also able to exert an inhibitory effect on in vivo bone resorption.
      Experimental periodontitis was induced by ligature wire tied around the contact
      between the first and second maxillary molars. Insertion of ligature wire for 7
      days induced alveolar bone destruction by activating osteoclasts. Oral
      administration of FR202126 (u.i.d.) significantly prevented alveolar bone loss in
      experimental periodontitis which may offer a new approach to treatment of
      periodontal disease.

PMID- 16404137
TI  - Metabolic transformation of dinophysistoxin-3 into dinophysistoxin-1 causes human
      intoxication by consumption of O-acyl-derivatives dinophysistoxins contaminated
      shellfish.
AB  - This paper describes for the first time a massive intoxication episode due to
      consumption of shellfish contaminated with 7-O-acyl-derivative dinophysistoxin-1,
      named Dinophysistoxin-3 (DTX-3). 7-O-acyl-derivative dinophysistoxin-1, a
      compound recently described in the literature, was found in shellfish samples
      collected in the Chilean Patagonia fjords. This compound does not inhibit Protein
      Phosphatases and also does not elicit the symptoms described for Diarrheic
      Shellfish Poisoning (DSP). The data showed here, give evidence of metabolic
      transformation of 7-O-acyl-derivative dinophysistoxin-1 (DTX-3) into
      Dinophysistoxin-1 (DTX-1, Methyl-Okadaic acid) in intoxicated patients. This
      metabolic transformation is responsible for the diarrheic symptoms and the
      intoxication syndrome showed by patients that consumed contaminated shellfish,
      which showed only the presence of 7-O-acyl-derivative dinophysistoxin-1. Patients
      fecal bacterial analysis for the presence of enteropathogens was negative and the
      mouse bioassay for DSP, performed as described for regulatory testing, was also
      negative. The HPLC-FLD and HPLC-MS analysis showed only the presence of DTX-3 as
      the only compound associated to DSP toxins in the contaminated shellfish samples.
      No other DSP toxins were found in the shellfish sample extracts. However, the
      patient fecal samples showed DTX-1 as the only DSP toxins detected in fecal.
      Moreover, the patient fecal samples did not show DTX-3. Since 7-O-acyl-derivative
      dinophysistoxin-1 (DTX-3) was the only compound associated to DSP toxins detected
      in the shellfish samples, an explanation for the diarrheic symptoms in the
      intoxicated patients would be the metabolic transformation of DTX-3 into DTX-1.
      This transformation should occur in the stomach of the poisoned patients after
      consuming 7-O-acyl-derivatives dinophysistoxin-1 (DTX-3) contaminated bivalves.

PMID- 16404139
TI  - Tissue- and dose-dependent alteration of stress-inducible proteins by beta2
      adrenoceptor agonist, salbutamol, in rats.
AB  - The effects of selective beta(2)-adrenoceptor agonists on proinflammatory
      cytokines and the expression of stress-inducible proteins have not yet been
      clarified. We investigated the effect of a higher dose (60 mg/kg intravenously)
      of salbutamol, a selective beta(2)-adrenoceptor agonist, on the induction of
      interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in plasma and
      the expression of protein and mRNA of metallothioein-1 (MT-1), heme oxygenase-1
      (HO-1) and inducible nitric oxide synthase (iNOS) in heart, lung, liver and
      spleen in rats. The plasma IL-6 concentration was significantly increased after
      administration with a maximum increase at 3 hr in a dose-dependent manner, but IL
      1beta and TNF-alpha concentrations were not changed. MT-1 mRNA increased in
      heart, lung and liver, but not in spleen, and MT-1 protein increased in
      endocardium, fibroblasts of lung and periportal regions in liver. HO-1 mRNA was
      not changed in lung, decreased at 3 hr in liver and spleen, and increased at 6 hr
      in liver. Contrary to liver, HO-1 mRNA in the heart increased at 3 hr and
      decreased at 6 hr. HO-1 protein increased in cardiomyocytes and centrilobular
      regions in the liver. iNOS mRNA increased in lung, liver and spleen, but
      decreased in the heart, and iNOS protein increased in alveolar type II cells and
      hepatocytes, and decreased in necrotic cardiomyocytes. In contrast, a lower dose
      (6 mg/kg intravenously) of salbutamol suppressed lipopolysaccharide-induced HO-1
      and iNOS mRNA. We conclude that salbutamol tissue- and dose-dependently alters
      the expression of stress-inducible proteins.

PMID- 16404141
TI  - Paired acute inhalation test reveals that acetaldehyde toxicity is higher in
      aldehyde dehydrogenase 2 knockout mice than in wild-type mice.
AB  - Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes
      acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the
      inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2); acute inhalation toxicity
      of acetaldehyde has not been evaluated in these populations. We compared the
      toxicity between wild-type (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-)
      mice by using the paired acute inhalation test modified from the acute toxic
      class method (OECD TG433). Blood acetaldehyde level was measured 4 hr after the
      inhalation. A pair of Aldh2+/+ and Aldh2-/- mice was put into a chamber and was
      exposed to 5000 ppm of acetaldehyde. At the start of the inhalation, the mice
      exhibited hypoactivity and closing of the eyes. Subsequently, symptoms such as
      crouching, bradypnea, and piloerection were observed. Flushing was observed only
      in the Aldh2+/+ mice. Symptoms such as tears, straggling gait, prone position,
      pale skin, abnormal deep respiration, dyspnea, and one case of death were
      observed only in the Aldh2-/- mice. The symptoms did not change 1 hr after
      inhalation in the Aldh2+/+ mice. In contrast, in the Aldh2-/- mice, the symptoms
      became more severe until the end of the inhalation. The blood acetaldehyde level
      in the Aldh2-/- mice was approximately twice that in the Aldh2+/+ mice 4 hr after
      inhalation. The Aldh2-/- mice evidently showed more severe toxicity as compared
      with the Aldh2+/+ mice due to acute inhalation of acetaldehyde at a concentration
      of 5000 ppm. Acetaldehyde toxicity in Aldh2+/+ and Aldh2-/- mice was estimated
      and classified one class different. Based on this study, acetaldehyde inhalations
      were inferred to pose a higher risk to ALDH2-inactive human individuals.

PMID- 16404140
TI  - Aldehyde dehydrogenase 2 activity affects symptoms produced by an intraperitoneal
      acetaldehyde injection, but not acetaldehyde lethality.
AB  - Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes
      acetaldehyde. Approximately 45% of Chinese and Japanese individuals are inactive
      ALDH2 phenotype; acute acetaldehyde toxicity has not been evaluated in these
      populations. We compared the acute acetaldehyde toxicity between wild-type
      (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-) mice who were administered an
      intraperitoneal (ip) injection of a single dose of acetaldehyde. This comparison
      was made based on the LD(50) values of acetaldehyde and the symptoms following
      the ip injection. Blood acetaldehyde level was measured in the 400 mg/kg dose
      group. Immediately after administration of acetaldehyde, the mice exhibited
      hypoactivity and staggering gait. Subsequently, symptoms such as pale skin, prone
      position, coma, and abnormal deep respiration were observed. In cases of death,
      dyspnea, wheezing, and hypothermia were observed from 15 to 30 min after the
      administration. In cases of survival, crouching, bradypnea, flushing and
      piloerection were observed. Significant latency of symptom recovery was found in
      the Aldh2+/- mice as compared with the Aldh2+/+ mice; however, no statistical
      difference was observed in the acetaldehyde LD(50) values. This might be
      attributable to the absence of a significant difference in the blood acetaldehyde
      concentrations in both mice during the first 0-15 min following administration;
      however, acetaldehyde elimination delay was observed in the Aldh2-/- mice as
      compared with the Aldh2+/+ mice. Acetaldehyde toxicity difference was observed
      between the Aldh2+/+ and Aldh2-/- mice; however, no difference in acetaldehyde
      lethality was observed by administration of a single dose of an ip acetaldehyde
      injection.

PMID- 16404142
TI  - Toxicity studies of tetradecanoic acid, 2-sulfo-, 1-methylester, sodium salt (C14
      MES).
AB  - We evaluated the toxicity of tetradecanoic acid methyl ester sodium salt (C14
      MES), a major component of fabric detergents, following the test guidelines of
      the Organization for Economic Cooperation and Development. The rat acute oral
      LD(50) was 1,000 mg/kg in males and 500 mg/kg in females. Applying the combined
      repeated dose and reproductive/developmental toxicity screening test (ReproTox),
      we exposed groups of Crj:CD (SD) IGS rats to C14-MES in the diet at
      concentrations of 0, 0.3, 0.6, or 1.2%. We observed decreases in fibrinogen
      levels and longer prothrombin time at the 1.2% treated level in females and
      decreases in serum triglyceride levels in both sexes at the 0.6% and 1.2%
      treatment levels, but the effects were not clinically significant. The no
      observed-effect-level (NOEL) for repeated dose toxicity was 0.3% (175 mg/kg body
      weight/day for males, 249 for females). The NOEL for reproduction/developmental
      toxicity was 1.2% (740 mg/kg for males, 1039 for females). C14-MES was negative
      in the reverse gene mutation assay and the chromosomal aberration test and did
      not induce skin sensitization in the guinea pig maximization test. These data
      confirm that C14-MES is of low hazard potential.

PMID- 16404143
TI  - PRIP, a novel Ins(1,4,5)P3 binding protein, functional significance in Ca2+
      signaling and extension to neuroscience and beyond.
AB  - Investigation of chemically synthesized inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] analogs has led to the isolation of a novel binding protein with a
      molecular size of 130 kDa, characterized as a molecule with similar domain
      organization to phospholipase C-d1 (PLC-d1) but lacking the enzymatic activity.
      An isoform of the molecule was subsequently identified, and these molecules have
      been named PRIP (PLC-related, but catalytically inactive protein), with the two
      isoforms named PRIP-1 and -2. Regarding its ability to bind Ins(1,4,5)P3 via the
      pleckstrin homology domain, the involvement of PRIP-1 in Ins(1,4,5)P3-mediated
      Ca2+ signaling was examined using COS-1 cells overexpressing PRIP-1 and cultured
      neurons prepared from PRIP-1 knock-out mice. Yeast two hybrid screening of a
      brain cDNA library using a unique N-terminus as bait identified GABARAP (GABAA
      receptor associated protein) and PP1 (protein phosphatase 1), which led us to
      examine the possible involvement of PRIP in GABAA receptor signaling. For this
      purpose PRIP knock-out mice were analyzed for GABAA receptor function in relation
      to the action of benzodiazepines from the electrophysiological and behavioral
      aspects. During the course of these experiments we found that PRIP also binds to
      the b-subunit of GABAA receptors and PP2A (protein phosphtase 2A). Here, we
      summarize how PRIP is involved in Ins(1,4,5)P3-mediated Ca2+ signaling and GABAA
      receptor signaling based on the characteristics of binding molecules.

PMID- 16404145
TI  - Molecular genetic analysis of ancient cattle bones excavated from archaeological
      sites in Jeju, Korea.
AB  - Ancient cattle bones were excavated from archaeological sites in Jeju, Korea. We
      used molecular genetic techniques to identify the species and establish its
      relationship to extant cattle breeds. Ancient DNA was extracted from four
      sources: a humerus (Gonae site, A.D. 700-800), two fragments of radius, and a
      tooth (Kwakji site, A.D. 0-900). The mitochondrial DNA (mtDNA) D-loop regions
      were cloned, sequenced, and compared with previously reported sequences of
      various cattle breeds (9 Asian, 8 European, and 3 African). The results revealed
      that these bones were of the breed, Bos taurus, and a phylogenetic tree indicated
      that the four cattle bones formed a monophyletic group with Jeju native black
      cattle. However, the patterns of sequence variation and reports from
      archaeological sites suggest that a few wild cattle, with a different maternal
      lineage, may have existed on Jeju Island. Our results will contribute to further
      studies of the origin of Jeju native cattle and the possible existence of local
      wild cattle.

PMID- 16404144
TI  - Painful channels in sensory neurons.
AB  - Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain
      sensation in some way protects body from imminent threat or injury. Peripheral
      sensory nerves innervated to peripheral tissues initially respond to multiple
      forms of noxious or strong stimuli, such as heat, mechanical and chemical
      stimuli. In response to these stimuli, electrical signals for conducting the
      nociceptive neural signals through axons are generated. These action potentials
      are then conveyed to specific areas in the spinal cord and in the brain. Sensory
      afferent fibers are heterogeneous in many aspects. For example, sensory nerves
      are classified as Aa, -b, -d and C-fibers according to their diameter and degree
      of myelination. It is widely accepted that small sensory fibers tend to respond
      to vigorous or noxious stimuli and related to nociception. Thus these fibers are
      specifically called nociceptors. Most of nociceptors respond to noxious
      mechanical stimuli and heat. In addition, these sensory fibers also respond to
      chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are
      considered polymodal. Recent advance in research on ion channels in sensory
      neurons reveals molecular mechanisms underlying how various types of stimuli can
      be transduced to neural signals transmitted to the brain for pain perception. In
      particular, electrophysiological studies on ion channels characterize biophysical
      properties of ion channels in sensory neurons. Furthermore, molecular biology
      leads to identification of genetic structures as well as molecular properties of
      ion channels in sensory neurons. These ion channels are expressed in axon
      terminals as well as in cell soma. When these channels are activated, inward
      currents or outward currents are generated, which will lead to depolarization or
      hyperpolarization of the membrane causing increased or decreased excitability of
      sensory neurons. In order to depolarize the membrane of nerve terminals, either
      inward currents should be generated or outward currents should be inhibited. So
      far, many cationic channels that are responsible for the excitation of sensory
      neurons are introduced recently. Activation of these channels in sensory neurons
      is evidently critical to the generation of nociceptive signals. The main channels
      responsible for inward membrane currents in nociceptors are voltage-activated
      sodium and calcium channels, while outward current is carried mainly by potassium
      ions. In addition, activation of non-selective cation channels is also
      responsible for the excitation of sensory neurons. Thus, excitability of neurons
      can be controlled by regulating expression or by modulating activity of these
      channels.

PMID- 16404146
TI  - Gamma-irradiation and doxorubicin treatment of normal human cells cause cell
      cycle arrest via different pathways.
AB  - Ionizing radiation and doxorubicin both produce oxidative damage and double
      strand breaks in DNA. Double-strand breaks and oxidative damage are highly toxic
      and cause cell cycle arrest, provoking DNA repair and apoptosis in cancer cell
      lines. To investigate the response of normal human cells to agents causing
      oxidative damage, we monitored alterations in gene expression in F65 normal human
      fibroblasts. Treatment with g-irradiation and doxorubicin altered the expression
      of 23 and 68 known genes, respectively, with no genes in common. Both agents
      altered the expression of genes involved in cell cycle arrest, and arrested the
      treated cells in G2/M phase 12 h after treatment. 24 h after g-irradiation, the
      percentage of G1 cells increased, whereas after doxorubicin treatment the
      percentage of G2/M cells remained constant for 24 h. Our results suggest that F65
      cells respond differently to g-irradiation- and doxorubicin-induced DNA damage,
      probably using entirely different biochemical pathways.

PMID- 16404147
TI  - Signaling through the murine T cell receptor induces IL-17 production in the
      absence of costimulation, IL-23 or dendritic cells.
AB  - IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory
      cytokines, and emerging evidence indicates that it plays a central role in
      inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T
      cells, but relatively little is known about how its expression is regulated. In
      the present study, we examined the requirements and mechanisms for IL-17
      expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced
      rapidly in primary T cells after stimulation of the T cell receptor (TCR) through
      CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is
      different in mice than in humans, because "costimulation" of T cells through CD28
      only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically
      enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB
      and CD40L exerted only very weak enhancing effects on IL-17 production. In
      agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression.
      However, IL-17 production can occur autonomously in T cells, as neither dendritic
      cells nor IL-23 were necessary for promoting short-term production of IL-17.
      Finally, to begin to characterize the TCR-mediated signaling pathway(s) required
      for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin
      A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and
      MAPK signaling pathways.

PMID- 16404148
TI  - Structure and tissue distribution of a trinucleotide-repeat-containing gene (cag
      3) expressed specifically in the mouse brain.
AB  - Using in silico approaches and RACE we cloned a full length trinucleotide (CAG)
      repeat-containing cDNA (cag-3). The cDNA is 2478 bp long and the deduced
      polypeptide consists of 140 amino acids of which 73 are glutamines. The genomic
      sequence spans approximately 79 kb on mouse chromosome 7 and the gene is composed
      of four exons. Standard and real-time PCR analyses of several mouse tissues
      showed that the gene is exclusively expressed in the brain and is not detected in
      embryonic stages. Within the brain, it is expressed throughout the forebrain
      region with predominant expression in the hypothalamus and olfactory bulb and
      very low levels in the mid- and hindbrain.

PMID- 16404149
TI  - Differential expression patterns of gangliosides in the ischemic cerebral cortex
      produced by middle cerebral artery occlusion.
AB  - Neuronal damage subsequent to transient cerebral ischemia is a multifactorial
      process involving several overlapping mechanisms. Gangliosides, sialic acid
      conjugated glycosphingolipids, reduce the severity of acute brain damage in
      vitro. However their in vivo effects on the cerebral cortex damaged by ischemic
      infarct are unknown. To assess the possible protective role of gangliosides we
      examined their expression in the cerebral cortex damaged by ischemic infarct in
      the rat. Ischemia was induced by middle cerebral artery (MCA) occlusion, and the
      resulting damage was observed by staining with 2, 3, 5-triphenylterazolium
      chloride (TTC). High-performance thin-layer chromatography (HPTLC) showed that
      gangliosides GM3 and GM1 increased in the damaged cerebral cortex, and
      immunofluorescence microscopy also revealed a significant change in expression of
      GM1. In addition, in situ hybridization demonstrated an increase in the mRNA for
      ganglioside GM3 synthase. These results suggest that gangliosides GM1 and GM3 may
      be synthesized in vivo to protect the cerebral cortex from ischemic damage.

PMID- 16404150
TI  - Crystallization and preliminary X-ray crystallographic analysis of PAS factor
      from Vibrio vulnificus.
AB  - Plasmid Achromobacter secretion (PAS) factor is a putative secretion factor that
      induces the secretion of periplasmic proteins. PAS factor from Vibrio vulnificus
      was crystallized at 294 K by the hanging drop vapor-diffusion method. It was
      isolated as a monomer during the purification procedures. The native crystal
      belongs to the F222 space group with unit cell parameters a=56.1, b=74.4, c=80.0
      A, a=b=g=90 degrees. The crystal was soaked in cryoprotectant containing 1 M NaBr
      for 1 h for MAD phasing. The diffraction limit of the Br-MAD data set was 1.9 A
      using synchrotron X-ray irradiation at beam line BL-18B at the Photon Factory,
      Japan.

PMID- 16404151
TI  - Sulforaphane inhibits osteoclastogenesis by inhibiting nuclear factor-kappaB.
AB  - We show that sulforaphane inhibits osteoclastogenesis in the presence of
      macrophage colony-stimulating factor (M-CSF) and receptor for activation of
      nuclear factor-kB ligand (RANKL) in osteoclast (OC) precursors. Sulforaphane, an
      aliphatic isothiocyanate, is a known cancer chemo-preventative agent with anti
      oxidative properties. Nuclear factor-kB (NF-kB) is a critical transcription
      factor in RANKL-induced osteoclastogenesis, and electrophoretic mobility shift
      assays (EMSAs) and assay of NF-kB-mediated secreted alkaline phosphatase (SEAP)
      revealed that sulforaphane selectively inhibited NF-kappaB activation induced by
      RANKL. Inhibition may involve interaction of sulforaphane with thiol groups,
      since it was prevented by reducing agents.

PMID- 16404152
TI  - Effect of the urease accessory genes on activation of the Helicobacter pylori
      urease apoprotein.
AB  - The roles that accessory gene products play in activating the Helicobacter pylori
      urease apoprotein were examined. The activity of the urease apoprotein increased
      in the following order when it was expressed with the accessory genes:
      ureG<ureGH<ureFGH<ureEFGH<ureIEFGH. Moreover, stepwise additions of ureE and ureI
      to ureFGH significantly increased urease activity. Urease apoproteins coexpressed
      with ureFGH, ureEFGH, and ureIEFGH had similar low chymotrypsin susceptibilities.
      In vivo and in vitro activation studies showed that the cooperative effect of the
      accessory proteins involved processes in which the UreFGH complex, UreE, and UreI
      were implicated. Thus, the UreFGH complex may serve to alter the conformation of
      the apoprotein into one that is more competent to assemble a stable
      metallocenter, and that facilitates cooperative effects.

PMID- 16404153
TI  - Mitogenic estrogen metabolites alter the expression of 17beta-estradiol-regulated
      proteins including heat shock proteins in human MCF-7 breast cancer cells.
AB  - Estrogen metabolites are carcinogenic. The comparative mitogenic activities of
      17b-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 4
      hydroxyestradiol (4-OHE2), 16a-hydroxyestrone (16a-OHE1) and 2-methoxyestradiol
      (2-ME), were determined in estrogen receptor(ER)-positive MCF-7 human breast
      cancer cells. Each of the E2 metabolites caused proliferation of the MCF-7 cells,
      but only E2 and 16a-OHE1 induced a greater than 20-fold increases in transcripts
      of the progesterone receptor (PR) gene, a classical ER-mediated gene. This
      suggests that the mitogenic action of E2 and 16a-OHE1 could result from their
      effects on gene expression via the ER. E2 metabolites altered the expression of
      E2-regulated proteins including heat shock proteins (Hsps). 16a-OHE1 and 2-ME as
      well as E2 increased levels of Hsp56, Hsp60, Hsp90a and Hsp110 transcripts, and
      the patterns of these inductions resembled that of PR. Hsp56 and Hsp60 protein
      levels were increased by all the E2 metabolites. Levels of the transcripts of 3
      E2-upregulated proteins (XTP3-transactivated protein A, protein disulfide
      isomerase-associated 4 protein and stathmin 1) and an E2-downregulated protein
      (aminoacylase 1) were also affected by the E2 metabolites. These results suggest
      that the altered expression of Hsps (especially Hsp56 and Hsp60) by E2
      metabolites such as E2, 16a-OHE1 and 2-ME could be closely linked to their
      mitogenic action.

PMID- 16404155
TI  - Molecular cloning of the DNA gyrase genes from Methylovorus sp. strain SS1 and
      the mechanism of intrinsic quinolone resistance in methylotrophic bacteria.
AB  - The genes encoding the DNA gyrase A (GyrA) and B subunits (GyrB) of Methylovorus
      sp. strain SS1 were cloned and sequenced. gyrA and gyrB coded for proteins of 846
      and 799 amino acids with calculated molecular weights of 94,328 and 88,714,
      respectively, and complemented Escherichia coli gyrA and gyrB temperature
      sensitive (ts) mutants. To analyze the role of type II topoisomerases in the
      intrinsic quinolone resistance of methylotrophic bacteria, the sequences of the
      quinolone resistance-determining regions (QRDRs) in the A subunit of DNA gyrase
      and the C subunit (ParC) of topoisomerase IV (Topo IV) of Methylovorus sp. strain
      SS1, Methylobacterium extorquens AM1 NCIB 9133, Methylobacillus sp, strain SK1
      DSM 8269, and Methylophilus methylotrophus NCIB 10515 were determined. The
      deduced amino acid sequences of the QRDRs of the ParCs in the four methylotrophic
      bacteria were identical to that of E. coli ParC. The sequences of the QRDR in
      GyrA were also identical to those in E. coli GyrA except for the amino acids at
      positions 83, 87, or 95. The Ser83 to Thr substitution in Methylovorus sp. strain
      SS1, and the Ser83 to Leu and Asp87 to Asn substitutions in the three other
      methylotrophs, agreed well with the minimal inhibitory concentrations of
      quinolones in the four bacteria, suggesting that these residues play a role in
      the intrinsic susceptibility of methylotrophic bacteria to quinolones.

PMID- 16404154
TI  - Characterization of rice mutants with enhanced susceptibility to rice blast.
AB  - As a first step towards identifying genes involving in the signal transduction
      pathways mediating rice blast resistance, we isolated 3 mutants lines that showed
      enhanced susceptibility to rice blast KJ105 (91-033) from a T-DNA insertion
      library of the japonica rice cultivar, Hwayeong. Since none of the susceptible
      phenotypes co-segregated with the T-DNA insertion we adapted a map-based cloning
      strategy to isolate the gene(s) responsible for the enhanced susceptibility of
      the Hwayeong mutants. A genetic mapping population was produced by crossing the
      resistant wild type Hwayeong with the susceptible cultivar, Nagdong. Chi-square
      analysis of the F2 segregating population indicated that resistance in Hwayeong
      was controlled by a single major gene that we tentatively named Pi-hy. Randomly
      selected susceptible plants in the F2 population were used to build an initial
      map of Pi-hy. The SSLP marker RM2265 on chromosome 2 was closely linked to
      resistance. High resolution mapping using 105 F2 plants revealed that the
      resistance gene was tightly linked, or identical, to Pib, a resistance gene with
      a nucleotide binding sequence and leucine-rich repeats (NB-LRR) previously
      isolated. Sequence analysis of the Pib locus amplified from three susceptible
      mutants revealed lesions within this gene, demonstrating that the Pi-hy gene is
      Pib. The Pib mutations in 1D-22-10-13, 1D-54-16-8, and 1C-143-16-1 were,
      respectively, a missense mutation in the conserved NB domain 3, a nonsense
      mutation in the 5th LRR, and a nonsense mutation in the C terminus following the
      LRRs that causes a small deletion of the C terminus. These findings provide
      evidence that NB domain 3 and the C terminus are required for full activity of
      the plant R gene. They also suggest that alterations of the resistance gene can
      cause major differences in pathogen specificity by affecting interactions with an
      avirulence factor.

PMID- 16404157
TI  - Drosophila melanogaster is susceptible to Vibrio cholerae infection.
AB  - Infection of Drosophila melanogaster adults with 6 Vibrio species revealed that
      V. cholerae was lethal (100% mortality) within 20 h as a result of systemic
      infection. Avirulent infection by V. vulnificus restricted the subsequent
      virulent infection by V. cholerae. The immediate transcription of antimicrobial
      peptides (AMPs), most notably Attacin A, was delayed in V. cholerae infection
      compared to V. vulnificus infection. Ectopic expression of Attacin A and
      Metchnikowin enhanced the survival of D. melanogaster upon V. cholerae infection.
      These results suggest that AMPs are important in the response to infections by
      Vibrio species and that the signaling pathways governing their expression may be
      targeted by V. cholerae virulence factors to elude the innate immunity of
      Drosophila.

PMID- 16404156
TI  - Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against
      neuronal cell death.
AB  - Reactive oxygen species (ROS) contribute to the development of various human
      diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which
      cells counteract the deleterious effects of ROS. SOD activity is dependent upon
      bound copper ions supplied by its partner metallochaperone protein, copper
      chaperone for SOD (CCS). In the present study, we investigated the protective
      effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1
      CCS was added to the culture medium of neuronal cells, it rapidly entered the
      cells and protected them against paraquat-induced cell death. Moreover,
      transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells.
      Immunohistochemical analysis revealed that it prevented neuronal cell death in
      the hippocampus in response to transient forebrain ischemia. These results
      suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS
      provides a potential strategy for therapeutic delivery in various human diseases
      including stroke related to SOD or ROS.

PMID- 16404159
TI  - Methylation changes of lysine 9 of histone H3 during preimplantation mouse
      development.
AB  - Immediately after fertilization, a chromatin remodeling process in the oocyte
      cytoplasm extracts protamine molecules from the sperm-derived DNA and loads
      histones onto it. We examined how the histone H3-lysine 9 methylation system is
      established on the remodeled sperm chromatin in mice. We found that the paternal
      pronucleus was not stained for dimethylated H3-K9 (H3-m2K9) during pronucleus
      development, while the maternal genome stained intensively. Such H3-m2K9
      asymmetry between the parental pronuclei was independent of HP1b localization
      and, much like DNA methylation, was preserved to the two-cell stage when the
      nucleus appeared to be compartmentalized for H3-m2K9. A conspicuous increase in
      H3-m2K9 level was observed at the four-cell stage, and then the level was
      maintained without a visible change up to the blastocyst stage. The behavior of
      H3-m2K9 was very similar, but not identical, to that of 5-methylcytosine during
      preimplantation development, suggesting that there is some connection between
      methylation of histone and of DNA in early mouse development.

PMID- 16404158
TI  - Development of SCAR markers for early identification of cytoplasmic male
      sterility genotype in chili pepper (Capsicum annuum L.).
AB  - We previously used Southern blot analysis to detect restriction-length
      polymorphisms between male fertile and cytoplasmic male sterile (CMS) cytoplasms
      at the coxII and atp6 loci of the mtDNA of Capsicum annuum L. Two copies of atp6
      were found in each male fertile and CMS pepper lines. Interestingly, one of the
      copies of atp6 in CMS pepper was a 3'-truncated pseudogene. The open reading
      frame of the coxII gene was the same in the fertile (N-) and CMS (S-) lines.
      However, the nucleotide sequence in the S-cytoplasm diverged from that in the N
      cytoplasm 41 bp downstream of the stop codon. To develop CMS-specific sequence
      characterized amplified region (SCAR) markers, inverse PCR was performed to
      characterize the nucleotide sequences of the 5' and 3' flanking regions of
      mitochondrial atp6 and coxII from the cytoplasms of male fertile (N-) and CMS (S
      ) pepper plants. Based on these data, two CMS-specific SCAR markers, 607 and 708
      bp long, were developed to distinguish N-cytoplasm from S-cytoplasm by PCR. The
      CMS-specific PCR bands were verified for 20 cultivars containing either N- or S
      cytoplasm. PCR amplification of CMS-specific mitochondrial nucleotide sequences
      will allow quick and reliable identification of the cytoplasmic types of
      individual plants at the seedling stage, and assessment of the purity of F1 seed
      lots. The strategy used in this report for identifying CMS-specific markers could
      be adopted for many other crops where CMS is used for F1 seed production.

PMID- 16404160
TI  - Berberine inhibits the production of lysophosphatidylcholine-induced reactive
      oxygen species and the ERK1/2 pathway in vascular smooth muscle cells.
AB  - Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC)
      proliferation and migration, which has been proposed to initiate the intimal
      thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in
      Berberis aquifolium and many other plants. Recently, it has been shown to have
      beneficial effects on the cardiovascular system, such as anti-hyperglycemic and
      cholesterol-lowering activity. In this study, we investigated its effects on
      lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC
      induced DNA synthesis and cell proliferation in VSMCs, as well as migration of
      the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular
      signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity
      and the lysoPC-induced increases in intracellular reactive oxygen species (ROS).
      These results indicate that the inhibitory effects of berberine on lysoPC
      stimulated VSMC proliferation and migration are attributable to inhibition of ROS
      generation and hence of activation of the ERK1/2 pathway. This suggests that
      berberine has potential in the prevention of atherosclerosis and restenosis.

PMID- 16404161
TI  - TRPC4 is an essential component of the nonselective cation channel activated by
      muscarinic stimulation in mouse visceral smooth muscle cells.
AB  - Classical transient receptor potential channels (TRPCs) are thought to be
      candidates for the nonselective cation channels (NSCCs) involved in pacemaker
      activity and its neuromodulation in murine stomach smooth muscle. We aimed to
      determine the role of TRPC4 in the formation of NSCCs and in the generation of
      slow waves. At a holding potential of -60 mV, 50 mM carbachol (CCh) induced INSCC
      of amplitude [500.8+/-161.8 pA (n=8)] at -60 mV in mouse gastric smooth muscle
      cells. We investigated the effects of commercially available antibodies to TRPC4
      on recombinant TRPC4 expressed in HEK cells and CCh-induced NSCCs in gastric
      smooth muscle cells. TRPC4 currents in HEK cells were reduced from 1525.6+/-414.4
      pA (n=8) to 146.4+/-83.3 pA (n=10) by anti-TRPC4 antibody and INSCC amplitudes
      were reduced from 230.9+/-36.3 pA (n=15) to 49.8+/-11.8 pA (n=9). Furthermore,
      INSCC in the gastric smooth muscle cells of TRPC4 knockout mice was only 34.4+/
      10.4 pA (n=8) at -60 mV. However, slow waves were still present in the knockout
      mice. Our data suggest that TRPC4 is an essential component of the NSCC activated
      by muscarinic stimulation in the murine stomach.

PMID- 16404162
TI  - Backbone 1H, 15N, and 13C resonance assignments and secondary-structure of
      conserved hypothetical protein HP0894 from Helicobacter pylori.
AB  - HP0894 (SwissProt/TrEMBL ID O25554) is an 88-residue conserved hypothetical
      protein from Helicobacter pylori strain 26695 with a calculated pI of 8.5 and a
      molecular weight of 10.38 kDa. Proteins with sequence similarity to HP0894 exist
      in Vibrio choierae, Enterococcus faecalis, Campylobacter jejuni, Streptococcus
      pneumoniae, Haemophilus influenzae, Escherichia coli O157, etc. Here we report
      the sequence-specific backbone resonance assignments of HP0894. About 97.5%
      (418/429) of the HN, N, CO, Ca, Cbeta resonances of the 88 residues of HP0894
      were assigned. On the basis of these assignments, three helical regions and four
      strand regions were identified using the CSI program. This study is a
      prerequisite for calculating the solution structure of HP0894, and studying its
      interaction with its substrates, if any, and/or with other proteins.

PMID- 16404163
TI  - Grim stimulates Diap1 poly-ubiquitination by binding to UbcD1.
AB  - Diap1 is an essential Drosophila cell death regulator that binds to caspases and
      inhibits their activity. Reaper, Grim and Hid each antagonize Diap1 by binding to
      its BIR domain, activating the caspases and eventually causing cell death. Reaper
      and Hid induce cell death in a Ring-dependent manner by stimulating Diap1 auto
      ubiquitination and degradation. It was not clear that how Grim causes the
      ubiquitination and degradation of Diap1 in Grim-dependent cell death. We found
      that Grim stimulates poly-ubiquitination of Diap1 in the presence of UbcD1 and
      that it binds to UbcD1 in a GST pull-down assay, so presumably promoting Diap1
      degradation. The possibility that dBruce is another E2 interacting with Diap1 was
      examined. The UBC domain of dBruce slightly stimulated poly-ubiquitination of
      Diap1 in Drosophila extracts but not in the reconstitution assay. However Grim
      did not stimulate Diap1 poly-ubiquitination in the presence of the UBC domain of
      dBruce. Taken together, these results suggest that Grim stimulates the poly
      ubiquitination and presumably degradation of Diap1 in a novel way by binding to
      UbcD1 but not to the UBC domain of dBruce as an E2.

PMID- 16404168
TI  - Report from the techa river dosimetry review workshop held on 8-10 December 2003
      at The State Research Centre Institute of Biophysics, Moscow, Russia.
AB  - Large releases of fission products into the Techa River, in the Southern Urals,
      occurred in 1950 and 1951, during the early years of operation of the Mayak
      Production Association (Mayak PA), which produced plutonium for nuclear weapons.
      Increases of leukemia and of solid cancers with radiation dose have been noted in
      the population of about 30,000 people who lived in the settlements downstream of
      the site of the radioactive releases; that population has been studied for
      several decades by Russian scientists, notably in the framework of cooperation
      with American and European scientists. The radiation doses are currently
      estimated by means of the Techa River Dosimetry System-2000 (TRDS-2000).
      Recently, a scientist from Mayak PA has suggested in several publications that
      the doses calculated using TRDS-2000 might be underestimated substantially. A
      special international Workshop, held in Moscow on 8-10 December 2003, aimed to
      resolve some of the pressing issues related to the determination of the external
      and internal doses received by the Techa River population and to give
      recommendations on the further development of methodologies used for dose
      reconstruction. The authors of this article were selected by the organizers of
      the Workshop to draw the conclusions of the meeting. They express the view that,
      while the dose reconstruction system TRDS-2000 is basically sound, additional
      work is needed and the results of any epidemiological studies making use of TRDS
      2000 should be qualified as preliminary, pending resolution of several issues.
      The most important of these issues is the re-evaluation of the activities
      released, using additional information that could be obtained with the help of
      Mayak experts. Other specific suggestions aiming to improve the dose
      reconstruction methodology for the Techa River cohort, i.e., continued
      measurements of accumulated dose in environmental samples and human tissues,
      validation of external dose estimates with thermoluminescence measurements of
      bricks and with electron paramagnetic resonance measurements of teeth, estimation
      of individual doses instead of group doses, detailed account of the contributions
      to dose of medical examinations and of other releases from the Mayak complex, and
      careful assessment of the uncertainties, were made by the meeting participants.

PMID- 16404169
TI  - Uncertainties in aerosol deposition within the respiratory tract using the icrp
      66 model: a study in workers.
AB  - This study estimates uncertainties in aerosol deposition within the main regions
      of the human respiratory tract calculated using the ICRP 66 model. Uniform,
      triangular, normal, or lognormal distributions were assigned to the model
      parameters, which involve physical properties of aerosols, their inhalability,
      their thermo- and aerodynamic deposition efficiencies, and the anatomy,
      physiology, and exertion level of the individuals. Calculations were performed
      over a range of aerosol sizes from 0.01 to 50 mum. Monodispersed aerosols were
      characterized by their aerodynamic diameter (dae). Polydispersed aerosols were
      characterized by their activity median aerodynamic diameters (AMADs) and the
      geometric standard deviation (GSD) in diameter. Lognormal distributions of
      particle deposition were generally observed with low GSD (< 2). The highest
      uncertainties were observed within the deep lung for the smallest and the largest
      aerosol sizes, which were mainly due either to particle density or to aerodynamic
      deposition efficiencies and anatomical and physiological variability,
      respectively. In the case of diameters larger than 5 mum, uncertainties in the
      deep lung deposition were much more important for monodispersed than for
      polydispersed aerosols. This was explained both by the size distribution of the
      deposited aerosol, the median of which corresponded to a maximal dae value of
      about 7 and 5 in bronchioles and alveoli, respectively, and by the absence of
      deposition, which occurs for dae equal to or larger than 50 mum, depending on the
      exertion level. Thus, in the range of AMADs considered, for the four default
      workers proposed by ICRP 66, uncertainties in aerosol deposition remain low, with
      GSD smaller than 3.

PMID- 16404170
TI  - Determination of 238u/235u, 236u/238u and uranium concentration in urine using sf
      icp-ms and mc-icp-ms: an interlaboratory comparison.
AB  - Accidental exposure to depleted or enriched uranium may occur in a variety of
      circumstances. There is a need to quantify such exposure, with the possibility
      that the testing may post-date exposure by months or years. Therefore, it is
      important to develop a very sensitive test to measure precisely the isotopic
      composition of uranium in urine at low levels of concentration. The results of an
      interlaboratory comparison using sector field (SF)-inductively coupled plasma
      mass spectrometry (ICP-MS) and multiple collector (MC)-ICP-MS for the measurement
      of uranium concentration and U/U and U/U isotopic ratios of human urine samples
      are presented. Three urine samples were verified to contain uranium at 1-5 ng L
      and shown to have natural uranium isotopic composition. Portions of these urine
      batches were doped with depleted uranium (DU) containing small quantities of U,
      and the solutions were split into 100 mL and 400 mL aliquots that were
      subsequently measured blind by three laboratories. All methods investigated were
      able to measure accurately U/U with precisions of approximately 0.5% to
      approximately 4%, but only selected MC-ICP-MS methods were capable of
      consistently analyzing U/U to reasonable precision at the approximately 20 fg L
      level of U abundance. Isotope dilution using a U tracer demonstrates the ability
      to measure concentrations to better than +/-4% with the MC-ICP-MS method, though
      sample heterogeneity in urine samples was shown to be problematic in some cases.
      MC-ICP-MS outperformed SF-ICP-MS methods, as was expected. The MC-ICP-MS
      methodology described is capable of measuring to approximately 1% precision the
      U/U of any sample of human urine over the entire range of uranium abundance down
      to <1 ng L, and detecting very small amounts of DU contained therein.

PMID- 16404171
TI  - Accumulation and distribution of uranium in rats after chronic exposure by
      ingestion.
AB  - Data describing the biokinetics of radionuclides after contamination come mainly
      from experimental acute exposures of laboratory animals and follow-up of
      incidental exposures of humans. These data were compiled to form reference models
      that could be used for dose calculation in humans. In case of protracted
      exposure, the same models are applied, assuming that they are not modified by the
      duration of exposure. This work aims at testing this hypothesis. It presents new
      experimental data on retention of uranium after chronic intake, which are
      compared to values calculated from a biokinetic model that is based on
      experiments of acute exposure of rats to uranium. Experiments were performed with
      56 male Sprague Dawley rats, from which 35 were exposed during their whole adult
      life to 40 mg L of uranyl nitrate dissolved in mineral water and 21 were kept as
      controls. Animals were euthanatized at 32, 95, 186, 312, 368, and 570 d after the
      beginning of contamination. Urine and all tissues were removed, weighted,
      mineralized, and then analyzed for uranium content by Kinetics Phosphorescence
      Analysis (KPA) or by ICP-MS. Experimental data showed that uranium accumulated in
      most organs, following a nonmonotonous pattern. Peaks of activities were observed
      at 1-3, 10, and 19 mo after the beginning of exposure. Additionally, accumulation
      was shown to occur in tissues such as teeth and brain that are not usually
      described as target organs. Comparison with model prediction showed that the
      accumulation of uranium in target organs after chronic exposure is overestimated
      by the use of a model designed for acute exposure. These differences indicate
      that protracted exposure to uranium may induce changes in biokinetic parameters
      when compared to acute contamination and that calculation of dose resulting from
      chronic intake of radionuclides may need specific models that are not currently
      available.

PMID- 16404172
TI  - Low frequency magnetic fields induced by car tire magnetization.
AB  - Alternating magnetic fields have been measured in a variety of different cars,
      the dominant contribution being from magnetized tires. Magnetic field strengths
      have been measured as a function of frequency directly at the tires and at
      different positions in rolling cars. Measurements at the tires showed field
      strengths up to 100 microtesla (microT). In the interior of rolling cars, close
      to the wheels at foot regions and at the back seat, field strengths of several
      microT were obtained in the 10-200 hertz (Hz) frequency domain. In some cases
      measured field values were considerably higher than those found in previous
      studies. Purposely magnetizing single tires made it possible to study the
      influence of various parameters. Degaussed tires retained low field values over
      prolonged time under conditions of normal use.

PMID- 16404173
TI  - A reanalysis of atomic-bomb cataract data, 2000-2002: a threshold analysis.
AB  - To obtain the best statistical model for a previous study of cataract prevalence
      in atomic-bomb survivors, we tested the fitness of the threshold model in an
      updated dataset of the study, utilizing re-diagnosis by a single ophthalmologist,
      use of the DS02 dosimetry system, and separation of the in utero group. The
      results suggest that, in 730 atomic-bomb survivors, we cannot conclude thresholds
      are greater than 0 Sv in cortical cataract and posterior sub-capsular opacity
      since the lower 90% confidence limits of the thresholds were 0 Sv. Threshold dose
      point estimates were 0.6 Sv (90% CI, <0.0-1.2 Sv) and 0.7 Sv (90% CI, <0.0-2.8
      Sv) for cortical cataract and posterior sub-capsular opacity, respectively.
      Detailed regression analyses with no threshold model showed that nuclear color
      and nuclear opacity have no dose responses (p > 0.40). Cortical cataract showed a
      significant dose effect (p = 0.002), with an odds ratio (OR)/Sv of 1.30 (95% CI,
      1.10-1.53) and no dose-effect modifiers. Posterior sub-capsular opacity showed a
      significant dose effect (p < 0.001), with an OR/Sv of 1.44 at age of exposure of
      10 y (95% CI, 1.19-1.73). The dose effect decreased significantly with increasing
      age at exposure (p = 0.022). No dose response was observed for in utero survivors
      (p > 0.20).

PMID- 16404174
TI  - The sliced bomab phantom: a new variant for intercomparison.
AB  - Previously, this laboratory conceptualized a new phantom for calibration or
      performance testing of whole body counters using Monte Carlo simulations. This
      paper describes the physical reality that was created from the Monte Carlo design
      project and compares its counting efficiency to that of a conventional BOMAB
      phantom using two whole body counters. In one counter (NaI based) the agreement
      between the two phantoms was +/-8% and in the second counter (Ge based) the
      agreement was +/-5% at all the energies measured (126 keV, 661 keV, 1172 keV,
      1330 keV). The advantage of the sliced phantom is that the sources are solid,
      sealed, and cannot leak activity thereby simplifying packing for shipment if the
      phantom is classified as a Dangerous Good. The new phantom is, therefore, ideal
      for uses that involve shipment, such as an intercomparison exercise. The phantom
      is also re-usable as the sources can be changed.

PMID- 16404175
TI  - Minimum detectable activity concentration in direct alpha spectrometry from
      outdoor air samples: continuous monitoring versus separate sampling and counting.
AB  - Rapid method for identifying the presence of alpha particle emitting
      radionuclides in outdoor air is of paramount importance should a nuclear or
      radiological incident occur. Minimum detectable activity concentrations of U, U,
      Pu, and Pu in outdoor air are calculated for two direct alpha spectrometry
      methods: continuous air monitoring is compared with separate sampling and
      subsequent alpha particle counting in a vacuum chamber. The radon progeny
      activity concentration typical for outdoor air and the effects for the alpha
      particle spectra caused by the properties of the filter and the aerosol particles
      are taken into account using measurements and Monte Carlo simulations. Continuous
      air monitoring is a faster method for identifying the presence of (trans)uranium
      elements when their activity concentration is considerably higher than the
      typical detection limit. Separate sampling and counting in a vacuum chamber is a
      more sensitive method when concentrations are close to the detection limit and
      when the duration of the sampling-counting cycle is greater than approximately 2
      h. The method may serve as a tool for rapid field measurements.

PMID- 16404176
TI  - Bone structure studies at The University of Leeds.

PMID- 16404182
TI  - Mustard to wine...aspects of the IAEA's recent work on the control of radioactive
      sources.
AB  - This paper reviews the International Atomic Energy Agency's "International
      Conference on the Safety and Security of Radioactive Sources: Towards a Global
      System for the Continuous Control of Sources throughout their Life Cycle," which
      was held in Bordeaux, France, from 27 June to 1 July 2005. Some high points of
      the progress in controlling radioactive sources since the similar meeting in
      Dijon (1998) are discussed. The impact of the IAEA's Code of Conduct on the
      Safety and Security of Radioactive Sources for radioactive material licensees in
      the United States of America is summarized.

PMID- 16404183
TI  - ALARA considerations for the whole body neutron irradiation facility source
      removal project at Brookhaven National Laboratory.
AB  - This paper describes the activities that were involved with the safe removal of
      fourteen PuBe sources from the Brookhaven National Laboratory (BNL) Whole Body
      Neutron Irradiation Facility (WBNIF). As part of a Department of Energy and BNL
      effort to reduce the radiological inventory, the WBNIF was identified as having
      no future use. In order to deactivate the facility and eliminate the need for
      nuclear safety management and long-term surveillance, it was decided to remove
      the neutron sources and dismantle the facility. In addition, the sources did not
      have DOT Special Form documentation so they would need to be encapsulated once
      removed for offsite storage or disposal. The planning and the administrative as
      well as engineering controls put in place enabled personnel to safely remove and
      encapsulate the sources while keeping exposure as low as reasonably achievable
      (ALARA).

PMID- 16404185
TI  - Nuclear medicine technologists and unauthorized self-injections.
AB  - An Office of Investigation (OI) investigation by the U.S. Nuclear Regulatory
      Commission (NRC) determined that, on three separate occasions over the past 10
      years, technologists in one licensed nuclear medicine program were injected with
      radiopharmaceuticals without Authorized User knowledge or approval. The most
      recent instance, the one that precipitated the investigation, was discovered by
      the licensee and self-reported to the NRC; the other two instances were
      discovered during the OI investigation and came as a complete surprise to the
      licensee. In a mediated Alternative Dispute Resolution (ADR) involving the
      licensee, a professional, independent mediator and representatives of the NRC, an
      agreement was worked out whereby the licensee would admit to the violations and
      work with the NRC to inform other licensees that this is not an acceptable
      practice and that there are additional precautions that licensees can and should
      take to assure that such violations do not happen on their watch.

PMID- 16404186
TI  - Characterization of surface soils at a former uranium mill.
AB  - Dawn Mining Company operated a uranium mill in Stevens County, Washington, from
      1957 to 1982, to process ore from the Midnite Mine, and from 1992 through 2000,
      to extract uranium from mine water treatment sludge. The mill was permanently
      shut down in 2001 when the Dawn Mining Company radioactive materials license was
      amended to allow direct disposal of water treatment sludge to a tailings disposal
      area at the mill. The mill building was demolished in 2003. Site soil
      characterization took place in 2004. Soil cleanup is ongoing. Contaminated soils
      on the site were characterized using a GPS-based gamma scanning system. A
      correlation between shielded gamma exposure rate and concentration of Ra in
      surface soils was developed. Subsurface soils were sampled using backhoe
      trenches. This system proved efficient and accurate in guiding development of the
      remedial action planning for the site and subsequent soil cleanup.

PMID- 16404187
TI  - Evaluation of a radiation survey training video developed from a real-time video
      radiation detection system.
AB  - This project incorporates radiation survey training into a real-time video
      radiation detection system, thus providing a practical perspective for the
      radiation worker on efficient performance of radiation surveys. Regular surveys
      to evaluate radiation levels are necessary not only to recognize potential
      radiological hazards but also to keep the radiation exposure as low as reasonably
      achievable. By developing and implementing an instructional learning system using
      a real-time radiation survey training video showing specific categorization of
      work elements, radiation workers trained with this system demonstrated better
      radiation survey practice.

PMID- 16404190
TI  - RSO interview with Rene Michel.

PMID- 16404188
TI  - A nontraditional method of providing radiation protection instruction at a large
      health science center.
AB  - In the 4 quarter of 2001 the University of Alabama at Birmingham (UAB) converted
      its traditional classroom radiation safety course, taught exclusively in a
      classroom setting four times each year, to a combined online-classroom format in
      which the majority of the course is taught online. This change was instituted in
      an effort to minimize the time spent in the classroom for UAB research personnel.
      This format should provide the additional benefit of self-paced instruction for
      course participants. The hypothesis that the combined online/lecture format was
      as effective as the lecture-only format was tested. A statistical analysis was
      performed on the average first-attempt test scores of the tests (number of tests
      = 334) taken during a 2-y period before the online transition (average score =
      75.5), and the average first-attempt test scores of the tests (number of tests =
      359) taken during a 2-y period after the online transition (average score =
      74.1.) A two-tailed Student's t-test was performed on the data. The t-value was
      1.73, and P (T< or = t) was 0.083. At alpha = 0.05, the null hypothesis that the
      two averages are equal cannot be rejected. Thus the online course format appears
      to be as effective a method of radiation safety instruction as the more
      traditional, exclusively-classroom method of instruction. This article also
      reviews steps under consideration to improve the current online course to make it
      a more effective tool in radiation safety instruction.

PMID- 16404192
TI  - The evolution of a revolution in nursing.

PMID- 16404193
TI  - Droplets of ideas.

PMID- 16404194
TI  - Generational diversity: impact on recruitment and retention of registered nurses.

PMID- 16404195
TI  - Longitudinal analyses of nurse staffing and patient outcomes: more about failure
      to rescue.
AB  - BACKGROUND: Numerous studies have examined cross-sectional data to determine the
      relationships between nurse staffing and patient outcomes. Questions have been
      raised about some of the studies now in the literature regarding the use of the
      hospital as the unit of analysis and the cross-sectional design of the studies.
      Additionally, there is a concern that the primary outcomes being studied are
      negative. OBJECTIVE: Objectives of this study are to (1) compare the
      relationships between nurse staffing and positive patient outcomes for 3 adult
      medical-surgical nursing units in one university teaching hospital across 4 years
      (16 fiscal quarters); and (2) explore the use of 2 new failure-to-rescue (FTR)
      rates as outcomes, specifically FTR from medication errors and FTR from decubitus
      ulcers. DESIGN: This study uses secondary analyses of data viewed retrospectively
      with a longitudinal repeated-measures design to estimate the relationships
      between nurse staffing and the outcomes of interest. RESULTS: Accounting for
      total dollars and case mix, all patient satisfaction measures increased as total
      hours of care per patient day increased, and as the skill mix became richer (more
      RN hours/total hours) there was a higher satisfaction with pain management and
      physical care requests. There was an increase in FTR from medication error as the
      non-RN (Other) hours of care per patient day increased and there was an increase
      in FTR from decubitus ulcers as patient severity increased. CONCLUSION: The
      overall conclusion is that it will likely be necessary to vary staffing hours and
      staffing mix depending on which positive patient outcome or outcomes you wish to
      achieve.

PMID- 16404196
TI  - Workplace incivility: state of the science.
AB  - The financial cost of workplace violence is 4.2 billion dollars a year. Workplace
      incivility may initiate a spiral that for 1,000 people a year ends in death at
      work. If an initial minor incident such as incivility could be mitigated, then
      the financial and human capital that could be realized by the healthcare
      organization is immense. This article is an in-depth look at the literature and
      theoretical frameworks related to workplace incivility.

PMID- 16404198
TI  - Application of the clinical nurse leader role in an acute care delivery model.
AB  - The authors describe a 6-month pilot project incorporating a modified version of
      the American Association of Colleges of Nursing's (AACN) clinical nurse leader
      (CNL) role as a prelude to implementation of the AACN-defined CNL role. The
      purpose of the project was to evaluate a new nursing care delivery model on a
      designated nursing unit, incorporating the modified CNL role. The pilot was
      evaluated using nurse-sensitive indicators. Results showed positive trends for
      all indicators.

PMID- 16404199
TI  - Effective strategies to increase reporting of medication errors in hospitals.
AB  - A major concern for patient safety in hospitals is accurate medication
      administration. To improve the medication administration process, nurses and
      pharmacists must report system problems. Although staff supported the concept of
      medication error reporting, they did not report errors. Inherent fear of
      retribution, punitive actions, and professional humiliation prevented self
      reporting of medication errors. Our hospital's quality improvement department
      developed, implemented, and evaluated a program called LifeSavers. Its purpose
      was to build a nonpunitive culture and to increase medication error reporting by
      staff. In one year, the LifeSavers program increased medication error disclosures
      from 14 to 72 reports per month. The successful development of a nonblame culture
      of medication error reporting led to identified sources of problems and
      improvement of the medication administration system.

PMID- 16404200
TI  - Evaluation of the Magnet Recognition Program.
AB  - Launched in the early 1980s, Magnet Recognition has been the focus of nurse
      administrators for over 2 decades in their quest for excellence in nursing
      practice and outcomes of patient care. The authors describe a comprehensive
      evaluation of the appraisal process within the Magnet Recognition Program
      commissioned by the American Nurses Credentialing Center and discusses
      recommendations for change in the program.

PMID- 16404201
TI  - The future is now: implementation of a tele-intensivist program.
AB  - Based on overwhelming scientific evidence, The Leapfrog Group focused on 3
      practices that have tremendous potential to save lives by reducing preventable
      mistakes in hospitals. The authors describe these practices and how they served
      as a driving force to create a "virtual ICU" within a Magnet hospital network.
      The effort combined services of a board-certified intensivist and technological
      advancements in telemedicine to ensure the delivery of high-quality care to all
      critically ill patients throughout the network. A computerized physician-order
      entry system, an electronic medication administration record, an electronic
      documentation system, and a remote ICU were the 4 programmatic phases necessary
      to realize the concept. The purpose of this article is to describe the process of
      planning and implementing the tele-intensivist program.

PMID- 16404205
TI  - Effect of health insurance on workplace absenteeism in the U.S. workforce.
AB  - OBJECTIVES: The objectives of this study were to examine the relationship between
      health insurance (HI) and number of missed workdays (MW), and how it is modified
      by level of access to care (AC) and healthcare use (HC). METHODS: The authors
      conducted a retrospective study of 1996-1999 Medical Expenditure Panel Survey of
      U.S. employees. RESULTS: Of 25,676 individuals, 13,957 (54%) reported MW (mean
      [standard deviation] = 4.3 [0.092]). Having HI was significantly associated with
      decreased likelihood of MW. Higher level of AC was significantly associated with
      greater number of MW. HC was significantly associated with increased likelihood
      of and greater number of MW. CONCLUSIONS: Having HI any time over the year is
      significantly associated with decreased likelihood of and smaller number of MW.
      HC use is an important explanatory variable and appears to be a confounder
      between HI and MW. The benefits to employers of ensuring that employees have
      health coverage should be explored.

PMID- 16404204
TI  - A retrospective occupational cohort study of end-stage renal disease in aircraft
      workers exposed to trichloroethylene and other hydrocarbons.
AB  - OBJECTIVE: Case-control studies suggest hydrocarbons increase end-stage renal
      disease (ESRD) risk. No cohort studies have been conducted. METHODS: An
      occupational database was matched to the U.S. Renal Data System, and the outcome
      of all-cause ESRD was examined using multivariable Cox regression. Sixteen
      individual hydrocarbons were studied, although exposures were not mutually
      exclusive. RESULTS: For the 1973-2000 period, there was an approximate twofold
      increased risk of ESRD among workers exposed to trichloroethylene, 1,1,1
      trichloroethane, and JP4 gasoline compared with unexposed subjects (all P <
      0.05). Relative risk was greater than unity (P > 0.05) for several other
      hydrocarbons. Associations attenuated (all P > 0.05) when 2001-2002 data were
      included in the analyses. CONCLUSIONS: Certain hydrocarbons may increase all
      cause ESRD risk. Uncertainty regarding the mechanism for increased risk and the
      observed attenuation in risk in 2001-2002, as well as the overlap of exposures,
      complicates interpretation. Additional research is needed.

PMID- 16404206
TI  - Obesity and mortality in a prospective study of a middle-aged industrial
      population.
AB  - BACKGROUND: Although obesity is an established risk factor for coronary heart
      disease and stroke mortality, its role as a risk factor for other causes of death
      has not been extensively investigated, particularly in an industrial population.
      METHODS: This prospective mortality study included 20 years of follow up of
      middle-aged industrial workers (n = 7139) at Shell Oil Company's manufacturing
      and research facilities. Baseline health risk factor data as of December 31,
      1983, and mortality data as of December 31, 2003, were extracted from the
      company's Health Surveillance System. Relative risks (RRs) for selected causes of
      death by body mass index (BMI) category were calculated using the Cox
      proportional hazards model adjusted for age, sex, and smoking status as well as
      other potential risk factors, ie, cholesterol, hypertension, and fasting blood
      glucose. RESULTS: Compared with employees with BMI between 18.5 and 24.9 kg/m,
      those with BMI of 30 kg/m or greater had a statistically increased RR (adjusted
      for age, sex, and smoking status) for all causes (RR, 1.25; 95% confidence
      interval [CI] = 1.03-1.51), coronary heart diseases (RR, 2.29; 95% CI = 1.50
      3.50), cardiovascular diseases (RR, 2.22; 95% CI = 1.51-3.27), diabetes (RR,
      16.97; 95% CI = 2.11-136.44), and accidental deaths (RR, 2.64; 95% CI = 1.23
      5.66). After adjusting for additional covariates, coronary heart diseases and
      cardiovascular diseases remained statistically significant. CONCLUSIONS: Obesity
      was associated with increased death rates for all causes, cardiovascular
      diseases, diabetes, and all accidents. Overweight individuals had a statistically
      lower cancer rate. Death rates for lung cancer and respiratory disease were lower
      among overweight/obese employees but did not reach statistical significance.
      Reductions of employee obesity can be an effective means of reducing these causes
      of death.

PMID- 16404207
TI  - Health-related quality of life, psychosocial work conditions, and absenteeism in
      an industrial sample of blue- and white-collar employees: a comparison of
      potential predictors.
AB  - PROBLEM: There is a scarcity of data simultaneously evaluating the relationship
      of health behavior, health perception, work characteristics, and demographic
      variables with sickness absenteeism in industrial employees. METHOD: Predictors
      and possible confounders (smoking, physical activity, alcohol intake, age,
      gender, body mass index, income) were regressed against frequency indices and the
      time lost index derived from the day-to-day absence data of 1524 employees at a
      manufacturing plant in Germany. Frequency indices were the number of sick-leave
      spells of 1, 2-3, 4-5, and >5 days within 1 year. RESULTS/CONCLUSION: Effort
      reward imbalance, lack of support by supervisors or coworkers, negative
      affectivity, exhaustion, and impaired health perception were significantly
      associated with absence spells and the time lost index. Job demands and job
      control as well as overcommitment were unrelated to absenteeism indices.
      Multivariate models suggest mediation through impaired health-related quality of
      life.

PMID- 16404208
TI  - A retrospective investigation of PM10 in ambient air and cardiopulmonary hospital
      admissions in Allegheny County, Pennsylvania: 1995-2000.
AB  - OBJECTIVE: Air quality in Allegheny County, Pennsylvania, has improved over the
      last decade, and we investigated whether the lower concentrations of fine
      particulate matter (PM10) are still associated with adverse health outcomes.
      METHODS: Daily cardiopulmonary hospital admissions in elderly residents of
      Allegheny County and countywide average PM10 measures were available from 1995
      through 2000. Using generalized additive models (GAM), a Poisson regression model
      was fit to the number of daily admissions using predictor variables: lags of
      PM10, daily temperature and humidity, day of the week, and time. RESULTS: Our
      findings suggest that there is a positive association of PM10 with hospital
      admissions, and the effect is related to current-day PM10 levels. CONCLUSIONS:
      Even at the lower levels of ambient air pollution as measured by PM10, there is
      still a suggestion of an adverse health effect in the elderly.

PMID- 16404209
TI  - Risk of lung cancer and exposure to industrial acids, solvents, and metals in
      leningrad province, Russia.
AB  - OBJECTIVE: We sought to investigate the association of occupational exposure to
      industrial acids, solvents, and metals with lung cancer in Leningrad Province,
      Russia, where an excess of occupationally related lung cancer was reported
      recently. METHODS: We identified 540 pathologically diagnosed lung cancer cases
      and 582 controls from the 1993-1998 autopsy records of the 88 Leningrad Province
      hospitals. Lifetime job-specific exposure measurements were available for 12
      industrial acids, 15 solvents, and 17 metals. RESULTS: Exposures were frequent in
      the study group and mostly occurred after World War II. However, lung cancer
      risks for industrial acids (odds ratio [OR] = 1.2; 95% confidence interval [CI] =
      0.8-1.7), solvents (OR = 0.8; 95% CI = 0.6-1.2), and metals (OR = 0.8; 95% CI =
      0.5-1.0) were not increased. Also, no significant excess risk was found for any
      of the specific agents investigated. CONCLUSIONS: The excess of occupationally
      related lung cancer in the Province is not explained by exposure to the agents
      investigated.

PMID- 16404210
TI  - The effect of women's occupational psychologic stress on outcome of fertility
      treatments.
AB  - OBJECTIVE: The objective of this study was to examine the possible association
      between women's occupational stress and outcome of fertility treatments. METHODS:
      A prospective cohort study was performed, including a consecutive group of 75
      working women with a female fertility problem attending fertility clinics between
      the years 1999 and 2000. A structured questionnaire measuring burnout, job
      strain, and job satisfaction was used. Workload was assessed by number of working
      hours and shift work. RESULTS: Women who perceived their job as more demanding
      were less likely to conceive (relative risk [RR], 0.6; 95% confidence interval
      [CI] = 0.42-0.96). Actual workload, measured by full-time versus part-time job,
      was found among women who conceived to be significantly associated with less
      likelihood to successfully complete a pregnancy (RR, 0.3; 95% CI = 0.11-0.96).
      CONCLUSIONS: An inverse association was found between perceived higher workload
      and conceiving. The likelihood to deliver after fertility treatment was
      associated with less working hours.

PMID- 16404211
TI  - Does arsenic exposure increase the risk for diabetes mellitus?
AB  - OBJECTIVE: Long-term arsenic exposure has been reported to associated with
      prevalence, incidence, and mortality of diabetes mellitus (DM). A tap water
      supply system was implemented in the early 1960s in the blackfoot disease (BFD)
      endemic areas. The objective of this study is to examine whether DM mortality
      decreased after the improvement of drinking water supply system through
      elimination of arsenic exposure from artesian well water. METHODS: Standardized
      mortality ratios (SMRs) for DM were calculated for the BFD endemic area for the
      years 1971-2000. RESULTS: The study results show that mortality from DM declined
      in females (but not in males) gradually after the improvement of drinking water
      supply system. CONCLUSIONS: Based on the reversibility criterion, the association
      between arsenic exposure and DM is likely to be casual for females but not in
      males.

PMID- 16404212
TI  - Postural balance changes in on-duty firefighters: effect of gear and long work
      shifts.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of long work
      shifts and turnout gear, including the self-contained breathing apparatus (SCBA)
      on firefighters' postural stability. METHODS: Sixteen firefighters were assessed
      using a portable forceplate system at the fire station. Postural sway parameters
      were recorded at the beginning of the work shift and repeated until the work
      shift ended. RESULTS: Task had the greatest impact on postural stability for all
      sway parameters. Turnout gear, with and without SCBA, improved postural
      stability. Postural stability decreased as firefighters spent more time on duty.
      CONCLUSIONS: Prolonged work shifts may be an important contributor to the high
      prevalence of slips and falls among firefighters. In all, the results indicate
      that many aspects of the firefighters' job may adversely impact their postural
      stability and potentially increase the risk of falling.

PMID- 16404213
TI  - New aspects of psychiatric morbidity in idiopathic environmental intolerances.
AB  - OBJECTIVE: To understand idiopathic environmental intolerances (IEI)-formerly
      multiple chemical sensitivities (MCS)-it is helpful to outline its characteristic
      psychiatric morbidity. METHOD: We applied a standardized interview according to
      the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID) to
      305 environmental patients with and without IEI. RESULTS: Somatoform, affective
      and anxiety disorders were the most frequent diagnoses but only slightly differed
      between patients with or without IEI. In both groups, current substance-related
      disorders were rare. We found a clearly higher prevalence of psychotic,
      especially current delusional disorders, in IEI. CONCLUSION: Somatization,
      depression, and anxiety are frequent in IEI but nonspecific. Psychotic disorders
      are more common in IEI than in other types of environmental illness. It appears
      worthwhile to study personality and cognitive style to explain the pivotal
      features of IEI.

PMID- 16404214
TI  - Pseudo-latex allergy associated with "latex" paint exposure: a potential cause of
      iatrogenic disability.
AB  - OBJECTIVE: We sought to describe outcomes for three health care workers with
      natural rubber latex (NRL) allergy reporting illness after exposure to latex
      paint. METHODS: We undertook a retrospective review of medical and occupational
      histories, diagnostic, treatment, and work recommendations. Outcomes included
      lost time, workers compensation indemnity costs, and return to work. RESULTS:
      None of the paints contained NRL. Cases 1 and 2 initially were misdiagnosed as
      suffering allergic reactions to NRL, resulting in 7 and 23 months lost time,
      $15,790 and $139,000 indemnity costs, respectively, and both failing to return to
      work. Case 3 was correctly diagnosed as not exposed to NRL, with only several
      lost days, no indemnity costs, and continued to work. CONCLUSIONS: The failure to
      recognize that synthetic paints do not contain NRL can lead to misdiagnosis,
      inappropriate exposure, and work avoidance recommendations and iatrogenic
      disability.

PMID- 16404215
TI  - Do gender, education, and income modify the effect of air pollution gases on
      cardiac disease?
AB  - OBJECTIVE: We sought to determine whether gender, education, and income influence
      the susceptibility to ambient air pollution. METHODS: We determined the
      association between daily cardiac hospitalizations and daily concentrations of
      gaseous air pollutants in 10 large Canadian cities using time-series analyses
      adjusted for day-of-the week, temperature, barometric pressure, relative
      humidity. RESULTS: Percentage increases in hospitalization associated with an
      increase in air pollution equivalent to its mean value were statistically
      significant for ozone, carbon monoxide and nitrogen dioxide individually (P <
      0.05) and the combined pollutant effect was 8.5% (95% confidence interval: 1.8,
      14.6). The air pollution-cardiac disease association was not significantly
      influenced by gender or community level of education or income. CONCLUSION: Short
      term changes in air pollution may adversely affect cardiac disease but gender,
      and community education and income do not accurately identify those with
      increased susceptibility.

PMID- 16404217
TI  - Occupational medicine forum.

PMID- 16404216
TI  - Medical surveillance of workers exposed to crystalline silica.

PMID- 16404221
TI  - PET and TNM: evolution or revolution?

PMID- 16404222
TI  - Ventricular mechanical dyssynchrony and resynchronization therapy in heart
      failure: a new indication for Fourier analysis of gated blood-pool radionuclide
      ventriculography.
AB  - In patients with decreased left ventricular ejection fraction and conduction
      disease, ventricular mechanical dyssynchrony has been demonstrated. To date,
      resynchronization by biventricular pacing is increasingly used since it improves
      ventricular function and exercise capacity in patients with heart failure. To
      optimize and evaluate the effect of resynchronization therapy and to identify
      patients who may benefit from biventricular pacing the assessment of left
      ventricular synchronicity is essential. Therefore, a non-invasive and
      reproducible technique to obtain information on ventricular synchrony is
      clinically valuable. In this review, the technical background and the role of
      phase analysis of gated blood-pool nuclear ventriculography in the assessment of
      ventricular mechanical synchrony, especially in heart failure patients subjected
      to biventricular pacing, will be discussed.

PMID- 16404223
TI  - Is stress-only imaging practical when a 1-day stress-rest 99mTc-tetrofosmin
      protocol is used?
AB  - OBJECTIVES: To investigate whether a significant number of normal 1-day stress
      rest 99mTc-tetrofosmin myocardial perfusion scintigraphy (MPS) studies can be
      identified from the low-dose stress acquisition alone, and whether technical
      staff can find such studies reliably. METHODS: The supervising consultant and
      four technologists independently graded the stress acquisitions from 200
      consecutive MPS studies using a five-point scale. Studies were classified as
      normal or abnormal according to the final clinical report based on the completed
      stress-rest protocol. RESULTS: Between 31 and 62 studies (16-31%) were classified
      as definitely normal from the stress acquisition alone, of which 0-4 (0-9%)
      proved abnormal on the final report. Of stress studies graded definitely normal
      by each technologist, the consultant disagreed in 13-34% of cases. Of 78 stress
      studies graded definitely normal by at least one technologist, 6% turned out to
      be abnormal and the consultant disagreed in 33%. When there was agreement between
      at least two technologists (57 studies), the rates fell to 4% and 21%
      respectively. CONCLUSIONS: Technologists could make the decision to avoid a
      resting study in up to 30% of patients following a normal low-dose stress
      acquisition. The supervising nuclear cardiologist would disagree in perhaps one
      in five cases, even when there was consensus between two or more technologists.
      These patients would suffer minor inconvenience by being recalled for a rest
      acquisition on a second day, but there would be important savings in time and
      radiation exposure for the majority.

PMID- 16404224
TI  - Early post-stress pulmonary uptake of 99mTc tetrofosmin during exercise (SPECT)
      myocardial perfusion imaging: correlation with haemodynamic, perfusion and
      function parameters.
AB  - OBJECTIVE: To test the association of early post-stress lung/heart ratio (LHR) of
      99mTc tetrofosmin radioactivity with gated-SPECT findings and angiographic
      results. METHODS: We studied 158 consecutive patients, with stress/rest 99mTc
      tetrofosmin myocardial SPECT and coronary angiography. Rest scans were obtained
      as gated SPECT and the left ventricular ejection fraction and end diastolic
      volume were calculated. To evaluate myocardial ischaemia, we calculated the
      summed stress score, summed rest score and summed difference score indices. For
      the LHR calculation, we acquired an anterior image, 4-6 min after radiotracer
      injection at stress; LHR was defined as mean counts/pixel in the lung region of
      interest divided by the mean counts/pixel in the myocardial region of interest.
      RESULTS: An early post-stress LHR value of 0.500 was defined as the upper normal
      limit. The most significant correlation (P<0.001) was observed among early post
      stress LHR, summed stress score and the number of stenosed vessels. The incidence
      of multi-vessel coronary artery disease in the subgroup of patients with
      increased values of early post-stress LHR, was significantly higher than in the
      normal group (81% vs. 42%, P<0.001). There was a significant difference (P<0.001)
      of the early post-stress LHR value between patients with normal coronary arteries
      or one-vessel disease and patients with multi-vessel disease. Early post-stress
      LHR was an independent predictor of multi-vessel coronary artery disease
      (coefficient 1.85, SD 0.16, P<0.001), with an incremental value for its
      identification. CONCLUSIONS: Our results suggest that early post-stress 99mTc
      tetrofosmin LHR appears to be a useful index of extensive myocardial ischaemia
      dysfunction and multi-vessel coronary artery disease.

PMID- 16404225
TI  - A model that accounts for the interdependence of extent and severity in the
      automatic evaluation of myocardial defects.
AB  - BACKGROUND: The extent and severity are two important parameters when describing
      a regional defect in myocardial single-photon emission computed tomography
      (SPECT) perfusion imaging. Intuitively, these two parameters should be
      independent of each other, but we have shown in a previous study that there is an
      interdependence. This interdependence has been investigated in two commercially
      available analysis programs (AutoQUANT and 4D-MSPECT) using Monte Carlo-simulated
      SPECT data. METHODS: An anthropomorphic digital computer phantom and a Monte
      Carlo program were used to generate SPECT data. Several defects of different
      volumes and lesion activity uptake reductions were simulated and evaluated.
      Comparison of the measures of extent and severity with their corresponding known
      values led to the development of a correction model based on least-squares
      parameter estimation. This model was then applied to a test group consisting of
      10 different computer-simulated patients. RESULTS: Our results showed that the
      interdependence was reduced significantly for most of our test cases after
      applying the correction method. The application of the correction model to the
      test group demonstrated that the model was robust with respect to different
      patient geometries. A further test with projections that simulated a perfect
      SPECT system revealed that the interdependence between the extent and severity
      was not caused by the limited spatial resolution of the SPECT system, but rather
      the inherent design of the algorithms of the analysis programs. CONCLUSIONS: A
      model has been developed to take into account the interdependence of the extent
      and severity.

PMID- 16404226
TI  - Correlation of preoperative thallium SPECT with histological grading and overall
      survival in adult gliomas.
AB  - BACKGROUND: The management and prognosis of a glioma depend on the tumour's
      histological grade. Thus, preoperative prediction of the grade is routinely
      needed to indicate whether surgery or biopsies are required. It has been proposed
      that thallium single photon emission computed tomography (SPECT), in a relative
      short series, will aid this prediction. AIM: To confirm the correlation between
      the results of preoperative thallium SPECT and grade of tumour as well as patient
      survival, and to define the cut-off value of the optimal thallium index for the
      detection of high grade gliomas in a large series of patients. METHODS: One
      hundred and eighteen patients treated for glioma were retrospectively included in
      this study. All patients underwent preoperative 201Tl SPECT upon initial
      presentation and were referred for neurosurgery. Initial scintigraphic findings
      were correlated with the histological grade of the tumour and overall patient
      survival. RESULTS: Thallium uptake was highly correlated with histological grade;
      the mean thallium indices for low grade and high grade gliomas were 1.8 and 4.9,
      respectively. On the basis of receiver operating characteristic analysis, the
      optimal cut-off value of the thallium index for the detection of high grade
      glioma was determined. By using 2.2 as the value for the threshold thallium
      index, the sensitivity and specificity were 93% and 72%, respectively. Kaplan
      Meier estimates of the overall survival curves, as a function of the thallium
      index, indicated that it was correlated with the overall survival (P<0.001).
      CONCLUSION: Thallium SPECT provides useful information about the histological
      grade of the tumour and overall patient survival. Additionally, in spite of its
      relatively weak resolution, it appears to be a powerful routine clinical tool for
      the management of gliomas.

PMID- 16404227
TI  - Early dynamic 201Tl SPECT in the evaluation of brain tumours.
AB  - OBJECTIVE: To estimate the usefulness of early dynamic 201Tl single photon
      emission computed tomography (SPECT) studies in distinguishing the histological
      malignancy of brain tumours. METHODS: Dynamic 201Tl SPECT was performed for 3 min
      per scan for 15 min immediately after the administration of 201TlCl in 110
      patients with brain tumours (111 lesions). The data obtained each 3 min were used
      for dynamic SPECT, and the five sets of data obtained were added to acquire
      static SPECT data. For static SPECT, the static thallium index (STI) was
      calculated as the ratio of 201Tl uptake in the tumour to that of the
      contralateral normal brain. The ratio of the 201Tl uptake for each 3 min was
      defined as the dynamic thallium index (DTI). The dynamic thallium rate (DTR), as
      a per cent, was calculated as DTR=(DTI for every 3 min)/STI H 100. The five
      values were approximated as a linear function and the slope (%/min) was
      calculated. RESULTS: In static SPECT, there was no significant difference between
      the STI of malignant tumours (glioblastoma and anaplastic astrocytoma) and that
      of benign tumours (low-grade glioma, meningioma, pituitary adenoma, neurinoma and
      haemangioblastoma) (3.7+/-1.5, 5.0+/-3.5, respectively). On dynamic SPECT, DTI
      increased markedly over 15 min for malignant tumours. In contrast, the DTI of
      benign tumours increased slightly, steadily or decreased. The slope of the linear
      functions calculated from the DTRs was much higher in the malignant tumour group
      than in the benign tumour group (P<0.001). CONCLUSIONS: We suggest that the
      performance of 201Tl dynamic SPECT for 15 min is useful for distinguishing
      malignant brain tumours from benign brain tumours and reduces the examination
      stress of patients.

PMID- 16404228
TI  - Functional interactions between entorhinal cortex and posterior cingulate cortex
      at the very early stage of Alzheimer's disease using brain perfusion single
      photon emission computed tomography.
AB  - OBJECTIVE: The cause of the reduced regional cerebral blood flow (rCBF) in the
      posterior cingulate cortex in the early stage of Alzheimer's disease has not been
      clarified. In Alzheimer's disease, the posterior cingulate cortex itself shows
      little neuropathologic degeneration, and a hypothesis explaining such a
      discrepancy is that the functional impairment in the posterior cingulate cortex
      reflects remote effects caused by degeneration in distant but connected areas,
      such as the entorhinal cortex. To test the hypothesis, we investigated the
      functional connectivity between the entorhinal cortex and posterior cingulate
      cortex. METHODS: Sixty-one patients with probable Alzheimer's disease at a very
      early stage and 61 age-matched healthy controls underwent both brain structural
      magnetic resonance imaging (MRI) and single-photon emission computed tomography
      (SPECT). Voxel-based morphometry was performed on MRI data to identify clusters
      of significantly reduced grey matter concentration in patients with Alzheimer's
      disease relative to controls, which were set as volumes of interest (VOIs) for
      correlation analyses of SPECT images. We then used adjusted rCBF values in the
      VOIs as covariates of interest in statistical parametric mapping. RESULTS: Voxel
      based morphometry demonstrated a significant reduction in grey matter
      concentration in the bilateral entorhinal cortex in Alzheimer's disease. A
      positive correlation between rCBF in the entorhinal cortex as VOI and that in the
      limbic and paralimbic systems, including the posterior cingulate cortex, anterior
      cingulate cortex, lingual gyri and left middle temporal gyrus (P<0.001), was
      observed in Alzheimer's disease. Control subjects also showed a similar
      correlation in the limbic and paralimbic systems, but not in the posterior
      cingulate cortex. CONCLUSION: These results indicate that rCBF changes in the
      posterior cingulate cortex may be closely related to those in the entorhinal
      cortex in patients with Alzheimer's disease, thereby supporting the 'remote
      effect' hypothesis.

PMID- 16404229
TI  - Cerebral perfusion heterogeneity and complexity in patients with acute
      subarachnoid haemorrhage.
AB  - BACKGROUND: The pathophysiological mechanisms of impaired perfusion during acute
      subarachnoid haemorrhage (SAH) are incompletely understood. Cerebral perfusion at
      the micro vascular level can be assessed by single photon emission computed
      tomography (SPECT). We used a SPECT approach with 99mTc-ECD to measure the
      cerebral perfusion heterogeneity and complexity in patients with acute aneurysmal
      SAH or perimesencephalic non-aneurysmal SAH (PNSAH). METHODS: The perfusion SPECT
      data of 61 patients with aneurysmal SAH, 18 patients with PNSAH, and 20 healthy
      control subjects were analysed by dividing the brain into 384 regions of
      interest. The magnitude of spatial perfusion heterogeneity was assessed by
      calculating the relative dispersion (RD=coefficient of variation). The fractal
      dimension (FD) was used to describe the overall complexity of global cerebral
      perfusion. RESULTS: Patients with aneurysmal SAH (RD=11.30+/-2.17, P<0.001) and
      PNSAH (10.38+/-2.27, P=0.023) had a higher perfusion heterogeneity than control
      subjects (8.69+/-0.80). Patients with aneurysmal SAH tended to have a higher
      perfusion heterogeneity than patients with PNSAH (P=0.061). Also the overall
      complexity of cerebral perfusion was decreased in aneurysmal SAH (FD=1.11+/-0.06,
      P<0.001) and PNSAH (1.11+/-0.06, P=0.004) as compared with control subjects
      (1.17+/-0.06). Acute SAH causes increased regional cerebral perfusion
      heterogeneity and decreased overall complexity of global cerebral perfusion.
      CONCLUSION: Non-invasive assessment of cerebral perfusion characteristics is
      feasible with SPECT and fractal analysis in patients with acute SAH and may help
      evaluating micro vascular function in SAH.

PMID- 16404230
TI  - The management of differentiated thyroid cancer using 123I for imaging to assess
      the need for 131I therapy.
AB  - BACKGROUND: Follow-up of 131I whole-body scanning after 131I ablation is
      associated with potential stunning. Previous studies have suggested that, for
      scanning, 123I is more sensitive than 131I in identifying thyroid tissue, but its
      specificity when positive is less certain. AIM: The use of 123I as an imaging
      agent in place of serial 131I imaging has been evaluated in the surveillance and
      treatment of differentiated thyroid carcinoma. RESULTS: A total of 186 studies in
      136 patients with differentiated thyroid carcinoma were evaluated after total or
      near total thyroidectomy followed by 131I ablation. In 125 studies 123I scanning
      was negative and no 131I therapy was given; four patients were positive on 123I
      scanning but for other reasons no 131I therapy was given. In 48/49 patients a
      positive 123I scan was followed by positive 131I therapeutic uptake. Only one
      patient failed to show positive uptake of I when first treated and she
      subsequently demonstrated uptake on a second therapy. CONCLUSION: High-dose 123I
      imaging is the correct predictor of the 131I post-therapy scan findings in most
      cases, at an administered activity that avoids stunning. As a diagnostic agent it
      is preferable to 131I in differentiated thyroid carcinoma.

PMID- 16404232
TI  - 99mTc-HMPAO labelled leucocyte scintigraphy in the diagnosis of pelvic
      inflammatory disease.
AB  - BACKGROUND: Scintigraphy using leucocytes labelled with 99mTc
      hexamethylpropyleneamine oxime (99mTc-HMPAO) is widely used for the localization
      of inflammatory foci and abscesses in cases of acute pelvic inflammatory disease,
      which is one of the serious health problems of women of child-bearing age. Early
      diagnosis and effective management of this condition can preserve fertility and
      prevent serious complications, such as peritonitis and sepsis. AIM: To evaluate
      the importance of scintigraphy using 99mTc-HMPAO labelled leucocytes in the early
      diagnosis of patients with pelvic inflammatory disease. METHODS: Fifteen women
      (mean age 29.2+/-8 years, range 25-46 years) with suspicion of pyogenic pelvic
      inflammatory disease based on gynaecological examinations, clinical findings and
      blood tests were included in this study. The patients received 555 MBq 99mTc
      HMPAO labelled leucocytes, by injection, and were scanned by scintigraphy 0.5-1,
      3 and 24 h later in the anterior abdominal projection. Ten of the patients were
      then evaluated by abdominal or transvaginal ultrasonography, four by computed
      tomography and two by both ultrasound and computed tomography. The final
      diagnosis was made by surgical intervention. RESULTS: Scintigraphy detected
      pelvic inflammatory disease in five of the patients. In three of them the disease
      was apparent on the scans taken at 0.5-1 h, and in the other two it was apparent
      at 3 h. There were no false negative results, and one false positive result. The
      scan accurately reflected the absence of pelvic inflammatory disease in nine
      patients showing non-pathological tracer uptake in the lower abdominal region.
      CONCLUSION: We showed that scintigraphy with 99mTc-HMPAO labelled leucocytes had
      a sensitivity of 100%, specificity of 90%, overall accuracy of 93%, positive
      predictive value of 83%, and negative predictive value of 100%. Therefore, we
      conclude that 99mTc-HMPAO labelled leucocyte scans provide a rapid and highly
      accurate method for diagnosing pelvic inflammatory disease in women of child
      bearing age. This adds an important contribution to the diagnosis of infection
      and helps determine further operative or conservative treatment.

PMID- 16404231
TI  - Localization of 131I-labelled monoclonal antibody ERIC1 in a subcutaneous
      xenograft model of neuroblastoma in SCID mice.
AB  - PURPOSE: To evaluate a novel strategy of immunolocalization of human
      neuroblastoma by targeting the neural cell adhesion molecule (NCAM), which is
      over-expressed on neuroblastoma. METHODS: NCAM expression on the cell surface of
      established neuroblastoma cells was shown by flow cytometry. A SCID mouse model
      using IMR5-75 neuroblastoma cells to induce subcutaneous tumour growth was
      established. 131I was used to label monoclonal NCAM specific ERIC1 antibodies
      generating the 131I-ERIC1 antibody, which showed a high affinity to NCAM also
      after labelling (KD=9 x 10(-8) mol . l(-1)). RESULTS: Measurement of organ
      specific radioactivity showed low organ-specific uptake (5.33%ID/g (percent of
      injected dose per gram of tissue) after 72 h), which continuously decreased over
      the 96 h investigation period, demonstrating clearance of radioactivity. In
      contrast, tumours accumulated radioactivity continuously up to a peak of
      42.07%ID/g at the 96 h time point (31.07%ID/g at 72 h). This specific uptake
      could be blocked by application of unlabelled ERIC1 antibodies. Measurement of
      blood specific radioactivity revealed a characteristic clearance over the first
      72 h. With 37 Gy, tumour-specific radioactivity reached therapeutic doses after
      96 h. CONCLUSIONS: These results indicate that 131I-labelled ERIC1 has the
      ability to probe NCAM-expressing tumour cells in vivo with high efficiency and is
      a promising reagent for the diagnosis and treatment of NCAM-positive human
      tumours, especially for neuroblastoma.

PMID- 16404234
TI  - Reproducibility of technetium-99m mercaptoacetyltriglycine clearance in patients
      with impaired renal function.
AB  - BACKGROUND: The aim of this study was to determine the reproducibility of
      technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) clearance in patients with a
      99mTc-MAG3 clearance below 100 ml/min/1.73 m2. METHODS: Two separate multi-sample
      clearance studies were performed in 16 patients at a 1 week interval. The
      clearances were calculated according to the open two-compartment model of
      Sapirstein et al., accepting the 90, 120 and 180 min samples as the last points
      of the biexponential curve. The clearance measurements were also performed
      according to the single-sample methods of Russell et al. and Bubeck using the
      fitted value at 44 min. RESULTS: There was no significant difference between the
      two clearance measurements for all five samples (P>0.05). There was a systematic
      increase in clearance measurements of 8.0+/-2.7% from the 180 to 120 min samples
      and 4.8+/-2.0% from the 120 to 90 min samples. Both single-sample methods (Bubeck
      and Russell et al.) gave more divergent results than multi-sample methods. The
      mean and standard deviation (%) of the normalized differences between two
      successive tests were -3.9+/-12.6, -2.4+/-13.1, -1.9+/-14.9, -4.1+/-53.5 and 
      13+/-82.1 for 90, 120 and 180 min samples and the Russell et al. and Bubeck
      methods, respectively. CONCLUSION: Single-sample methods give very poor
      reproducibility and accuracy and should not be used in patients with poor renal
      function. The reproducibility of 99mTc-MAG3 clearance using the multi-sample
      method (90 min) in patients with impaired renal function is 12.6%, which is
      similar to that in patients with good renal function and that obtained with other
      tubular agents. Whether this level of reproducibility is satisfactory for
      documenting serial changes in an individual patient with a 99mTc-MAG3 clearance
      below 100 ml/min/1.73 m2 depends on the expectation of the clinician.

PMID- 16404235
TI  - Preparation of 99mTc-MAG3: radiochemical purity is affected by the residence time
      of sodium chloride injection in a three-part syringe.
AB  - BACKGROUND: Routine technetium-99m mercaptoacetyltriglycine (99mTc-MAG3)
      radiochemical purity measurements have revealed occasional unacceptably low
      values. Preliminary investigations suggested a causal link with the residence
      time of sodium chloride injection in the syringe used to reconstitute the MAG3
      kit. OBJECTIVES: To investigate the cause of this phenomenon, determine how it
      can be avoided and establish whether it occurs with other 99mTc
      radiopharmaceuticals. METHODS: 99mTc-MAG3 was prepared by drawing sodium chloride
      injection into a lubricated, three-part, 10 ml Plastipak syringe and using it to
      reconstitute a MAG3 kit immediately or after a 15 min incubation period. The
      radiochemical purity was measured by high-performance liquid chromatography. The
      experiment was repeated using lubricant-free, two-part, Norm-Ject syringes and
      lubricated, two-part, Monoject syringes (15 min incubation only). To investigate
      the influence of Plastipak's rubber components on the radiochemical purity,
      samples were prepared using sodium chloride injection that had been incubated
      with lubricated or lubricant-free rubber plunger ends. Similar experiments were
      performed to determine the effect of Plastipak on 99mTc-exametazime, 99mTc
      sestamibi and 99mTc-tetrofosmin. RESULTS: The radiochemical purities of 99mTc
      MAG3 prepared with sodium chloride injection incubated for 0 and 15 min in
      Plastipak syringes were 96.4+/-0.5% and 89.4+/-5.5%, respectively. The difference
      was significant (P<0.05, n=10). With Norm-Ject syringes, the radiochemical
      purities were 96.5+/-0.5% and 96.6+/-0.5%, respectively. The difference was not
      significant (P>0.05, n=10). With Monoject syringes, the radiochemical purity was
      96.6+/-0.4% (n=10). 99mTc-MAG3 prepared using sodium chloride injection treated
      with lubricated and unlubricated syringe rubber plunger ends had radiochemical
      purities of 85.3+/-6.6% and 82.1+/-6.5% (n=5), respectively. The radiochemical
      purities of other 99mTc radiopharmaceuticals prepared using sodium chloride
      injection incubated for 0 or 15 min in Plastipak syringes were as follows: 99mTc
      exametazime, 95.3+/-0.6% and 94.5+/-1.8%; 99mTc-sestamibi, 98.0+/-0.6% and 97.7+/
      0.6%; 99mTc-tetrofosmin, 96.5+/-0.2% and 97.0+/-0.4%. None of the differences was
      significant (P>0.05, n=5). CONCLUSIONS: A lipophilic impurity, originating from
      the rubber plunger of a three-part Plastipak syringe, is formed in 99mTc-MAG3
      when the sodium chloride injection used to reconstitute the kit is in the syringe
      for a prolonged time. The effect is eliminated by using a two-part syringe or by
      injecting the sodium chloride injection into the kit immediately. The phenomenon
      does not occur with 99mTc-exametazime, 99mTc-sestamibi or 99mTc-tetrofosmin.

PMID- 16404233
TI  - Localized internal radiotherapy with 90Y particles embedded in a new
      thermosetting alginate gel: a feasibility study in pigs.
AB  - BACKGROUND: Internal radiotherapy requires the localization of the radionuclide
      to the site of action. A new injectable alginate gel formulation intended to
      undergo immediate gelation in tissues and capable of encapsulating radioactive
      particles containing 90Y was investigated. METHODS: The formulation was injected
      intramuscularly, into the bone marrow compartment of the femur and intravenously,
      respectively, in pigs. The distribution of radioactivity in various tissues was
      determined. RESULTS: Following intramuscular injection, more than 90% of the
      radioactivity was found at the site of injection. Following injection into bone
      marrow, 30-40% of the radioactivity was retained at the site of injection, but a
      considerable amount of radioactivity was also detected in the lungs (35-45%) and
      the liver (5-18%). Following intravenous injection, 80-90% of the radioactivity
      was found in the lungs. CONCLUSION: The present formulation appears suitable for
      localized radiotherapy in organs and tissues having low perfusion.

PMID- 16404238
TI  - Second to third phalanx vascularized bone transfer.

PMID- 16404237
TI  - Determining the optimal approach to breast reconstruction after partial
      mastectomy.
AB  - BACKGROUND: Unfortunately, patients who desire repair of contour deformities
      after partial mastectomy usually present after radiation therapy, which may
      increase the risk of complications and result in a poor aesthetic outcome. The
      authors reviewed their experience with repair of partial mastectomy defects to
      determine the optimal approach to breast reconstruction after partial mastectomy.
      METHODS: Sixty-nine patients who underwent repair of a partial mastectomy defect
      and received radiation therapy were included in this analysis. The reconstructive
      techniques were categorized as local tissue rearrangement (LTR), breast
      reduction, or use of a latissimus dorsi myocutaneous flap or thoracoepigastric
      skin flap (hereafter referred to as "flap"). RESULTS: Fifty patients underwent
      immediate reconstruction before radiation therapy, and 19 underwent delayed
      reconstruction after radiation therapy. The reconstructive techniques in patients
      with immediate reconstruction were local tissue rearrangement in 28 percent,
      breast reduction in 66 percent, and flaps in 6 percent. In patients with delayed
      reconstruction, 32 percent had local tissue rearrangement, 42 percent had breast
      reduction, and 26 percent had flaps. The complication rates for immediate and
      delayed reconstruction were 26 percent and 42 percent, respectively. Overall, and
      in the setting of immediate reconstruction, the flap technique was associated
      with a higher complication rate than local tissue rearrangement and breast
      reduction. However, in the setting of delayed reconstruction, the flap technique
      was associated with a lower complication rate than the other two techniques.
      Fifty-seven percent of the immediate reconstructions performed with the local
      tissue rearrangement or breast reduction technique, but only 33 percent of the
      immediate reconstructions performed with the flap technique, were associated with
      an excellent or good aesthetic outcome. CONCLUSION: Immediate repair of partial
      mastectomy defects with local tissues results in a lower risk of complications
      and better aesthetic outcomes than immediate repair of partial mastectomy defects
      with a latissimus dorsi flap.

PMID- 16404239
TI  - Horrifying basal cell carcinoma forearm lesion leading to shoulder
      disarticulation.

PMID- 16404240
TI  - Aesthetic management of the nasal component of naso-orbital ethmoid fractures.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Discuss the critical anatomic structures of the nose that are affected in
      naso-orbital ethmoid fractures. 2. Discuss the advantages of early, complete
      nasal reconstruction of these fractures. 3. Apply a clinical algorithm to such
      nasal reconstruction. 4. List the techniques used in aesthetic reconstruction of
      the nose in naso-orbital ethmoid fractures. BACKGROUND: Fractures of the naso
      orbital ethmoid complex pose challenging management issues. Although basic
      treatment principles have been well described, the aesthetic management of the
      nasal component has not been adequately addressed in the literature. METHODS:
      When secondary nasal deformities occur, they are difficult to correct. Optimal
      primary correction of the nasal deformity is accomplished using the following
      four principles: (1) rigid fixation of the nasal pyramid and restoration of nasal
      height and length; (2) restoration of tip projection; (3) septal
      reduction/reconstruction; and (4) lateral nasal wall augmentation. RESULTS:
      Successful management of naso-orbital ethmoid fractures is a complex and
      challenging task. Both the bony and soft-tissue components must be addressed and
      the extent of the injury must be adequately diagnosed to avoid omission of
      critical steps in the reconstruction. Inadequate treatment of naso-orbital
      ethmoid fractures can produce a severe cosmetic deformity that is very difficult
      to correct secondarily. CONCLUSION: The authors discuss the nasal component of
      naso-orbital ethmoid complex injuries and detail the key principles in their
      algorithm for aesthetic nasal reconstruction.

PMID- 16404242
TI  - Assessment of TRAM aesthetics: the importance of subunit integration.
AB  - BACKGROUND: Characterization of optimal aesthetics in transverse rectus abdominis
      musculocutaneous (TRAM) breast reconstruction is a challenge that even the most
      experienced breast surgeon faces. Aesthetic assessment in breast surgery has
      attempted to evaluate the reconstructed breast either as one cohesive entity or
      as a sum of its parts. The authors propose that the most advantageous assessment
      involves looking at the reconstructions in terms of aesthetic components, not
      necessarily in visual subunits. METHODS: The authors investigated the responses
      of five physicians and 12 nonphysician evaluators using various methods of
      aesthetic assessment, including, most importantly, a visual analogue scale
      survey. Pearson's correlation and intraclass correlation analyses were performed
      using SAS software. RESULTS: Their analysis determined that while all components
      of TRAM reconstruction were important, symmetry, contour, and breast positioning
      were consistently named the most important components of breast reconstruction.
      When the breast reconstruction was divided into aesthetic subunits, there was a
      high degree of correlation between the overall score and the subunit scores (r =
      0.81: r > 0.6 for good correlation). CONCLUSIONS: From these assessments, the
      authors derived a set of aesthetic rules for TRAM flap reconstruction. They
      believe that methodical application of these rules on a consistent basis can lead
      to the production of maximal aesthetic outcomes in TRAM breast reconstruction.

PMID- 16404243
TI  - Effect of pregnancy and breast-feeding on vertical mammaplasty.
AB  - BACKGROUND: A retrospective study was performed to evaluate the effect of
      pregnancy and breast-feeding on the breasts of women who had undergone vertical
      reduction mammaplasty. METHODS: The study group consisted of 57 women who had
      pregnancies after their vertical reduction mammaplasty. Of this group, 24 breast
      fed. The control group consisted of 103 women who had vertical mammaplasty but no
      subsequent pregnancies. An evaluation form was completed that included the age,
      body mass index, amount of tissue removed per breast, pregnancies after the
      mammaplasty, history of breast-feeding, and breast measurements. All patients had
      breast measurements routinely performed postoperatively at 2 weeks and again at 2
      years. The following measurements were obtained: mid-clavicle to nipple, and
      inframammary fold to inferior areola. RESULTS: No significant difference was
      found between the control and the study group regarding age (27 +/- 12 versus 29
      +/- 10), body mass index (26 +/- 5 versus 27 +/- 4), and grams of tissue excised
      per breast (610 +/- 201 versus 598 +/- 279). The breast measurement from the mid
      clavicle to nipple was not significantly altered by pregnancy with or without
      breast-feeding (p > 0.05). The distance between the inframammary fold and the
      inferior margin of the areola was significantly (p < 0.05) increased by pregnancy
      both with breast-feeding (4.1 +/- 2.3 cm) and without (3.5 +/- 2.6 cm) when
      compared with the control group (1.2 +/- 1.5 cm). CONCLUSION: The vertical
      mammaplasty has less tendency for pseudoptosis (bottoming out), but the
      alterations of breast volume brought about by pregnancy and breast-feeding may
      affect the final outcome of even this good reduction mammaplasty method.

PMID- 16404244
TI  - Enhancing patient outcomes in aesthetic and reconstructive breast surgery using
      triple antibiotic breast irrigation: six-year prospective clinical study.
AB  - BACKGROUND: Capsular contracture remains one of the most commonly reported
      complications in aesthetic and reconstructive breast patients. Previous in vitro
      studies from the authors' laboratory have recommended a new triple antibiotic
      povidone-iodine irrigation (2000) and subsequently a triple antibiotic non
      povidone-iodine-containing irrigant (2001) to optimize broad-spectrum coverage of
      various bacteria implicated in capsular contracture; however, the clinical
      efficacy of these in vitro studies remains unproven. The purpose of this study
      was to determine the clinical efficacy for the previously reported triple
      antibiotic breast irrigation. The cost-effectiveness of universal application of
      irrigation solutions in breast prosthesis surgery was analyzed as well. METHODS:
      Patients undergoing aesthetic and reconstructive breast implant procedures were
      treated with a standardized operative technique, including the use of triple
      antibiotic breast irrigation by a single surgeon. Capsular contracture was
      assessed using a simplified Baker scale and graded by two independent caregivers
      to maximize objectivity and consistency. Additional complications were also
      recorded, including reoperation. Patient charges for antibiotic irrigation and
      reoperation for contracture were determined and compared. RESULTS: A total of 335
      patients operated on since 1997 were evaluated prospectively. They ranged in age
      from 18 to 86 years, and the mean follow-up was 14 months (range, 6 to 75
      months). The rate of grade III/IV capsular contracture in the study groups was
      1.8 percent for patients undergoing primary breast augmentation. Patients
      undergoing augmentation-mastopexy had a grade III/IV contracture rate of 0
      percent. Breast reconstruction patients had a 9.5 percent rate of grade III/IV
      contracture. CONCLUSIONS: Triple antibiotic breast irrigation is clinically
      associated with a low incidence of capsular contracture compared with other
      published reports, and its clinical efficacy supports previously published in
      vitro studies. Application of triple antibiotic irrigation is recommended for all
      aesthetic and reconstructive breast procedures and is cost effective.

PMID- 16404246
TI  - Patient self-assessment of the cosmetic results of breast reconstruction.
AB  - BACKGROUND: In a previous study, the authors evaluated factors that contribute to
      patient satisfaction with breast reconstruction, using a comprehensive chart
      review and questionnaire. The results of part of this questionnaire, regarding
      patients' rating of the cosmetic result of their breast reconstruction, are
      presented in this article. METHODS: The questionnaire was mailed to 267 patients,
      214 questionnaires (80.1 percent) were returned, and 200 contained a response to
      the question rating the overall cosmetic outcome of breast reconstruction (Fig.
      1). To conduct a statistical analysis, the data were collapsed into two smaller
      groups. An "excellent" or "good" result was considered a "favorable" outcome,
      while lower responses were "unfavorable" outcomes. RESULTS: The outcome was rated
      as excellent by 82 patients, good by 76 patients, fair by 31 patients, and poor
      by 11 patients. A significant association was found between overall cosmesis and
      breast size, shape, or scars. CONCLUSION: It should not be assumed that patients'
      responses regarding satisfaction with reconstruction will reflect their specific
      feelings regarding cosmetic results.

PMID- 16404245
TI  - Perfusion zones of the DIEP flap revisited: a clinical study.
AB  - BACKGROUND: The Hartrampf perfusion zones of the lower abdominal flap are
      generally accepted. They were empirically based on the clinical impression of the
      perfusion in the first 16 unipedicled transverse rectus abdominis
      musculocutaneous flaps and have been uncritically adopted for the free transverse
      rectus abdominis musculocutaneous and the free deep inferior epigastric
      perforator (DIEP) flap. Scientific data proving the validity of these perfusion
      zones do not exist. The objective of this study was to evaluate and
      quantitatively assess the perfusion zones of the DIEP flap. METHODS: In a
      clinical, prospective study of 15 patients undergoing DIEP flap breast
      reconstruction, tissue perfusion was intraoperatively assessed using the method
      of laser-induced fluorescence of indocyanine green. RESULTS: Perfusion of zones
      I, II, and III was seen 25, 41, and 32 seconds, respectively, after injection,
      and the perfusion index constituted 76, 25, and 47 percent (median) of normal
      tissue. Perfusion of zone IV was completely absent in five patients (33 percent);
      in the remaining patients, it was dramatically decreased (5 percent) and occurred
      with a delay of 67 seconds. CONCLUSIONS: On the basis of the results of this
      study, the Hartrampf concept of a centrally perfused skin ellipse with declining
      perfusion of its peripheral ends is wrong and should be revised. Instead, one
      should think of the lower abdominal flap as two halves separated by the midline.
      The ipsilateral half has an axial pattern of perfusion; the contralateral half
      shows a random-pattern, individually variable blood supply. Therefore, the
      classic Hartrampf zones should be rearranged, switching zones II and III.

PMID- 16404248
TI  - Psychosocial factors predicting the motivation to undergo cosmetic surgery.
AB  - BACKGROUND: The present study investigates psychological factors expected to
      predict the motivation to undergo cosmetic surgery. It is hypothesized that body
      image, self-esteem, teasing history, acceptance of cosmetic surgery in the
      individual's environment, and self-monitoring relate to motivation to have
      cosmetic surgery. METHODS: Questionnaire data were obtained from 907 participants
      who responded to a survey distributed to a representative sample of Norwegian
      women aged 22 to 55 years. A second sample of 195 female prospective cosmetic
      surgery patients was recruited from a plastic surgery clinic. Measures of the
      hypothesized predictor variables were obtained from both samples. Surgery
      motivation was operationalized in two different ways. First, the women in the
      first sample were asked to indicate whether they wished to undergo cosmetic
      surgery, such that women who wished to have surgery could be compared with those
      who did not. Second, prospective patients were compared with women from the first
      sample who indicated that they did not wish to have cosmetic surgery. RESULTS:
      Analyses revealed all predictor variables but self-esteem to be related to either
      the wish or the decision to undergo surgery, or to both. Social acceptance of
      cosmetic surgery and body image were the strongest predictors of cosmetic surgery
      motivation. CONCLUSIONS: The study gives new insights into psychological factors
      predicting cosmetic surgery motivation. Furthermore, the influence of social
      factors on cosmetic surgery motivation is emphasized, and it is suggested that
      these factors be included in future research designs.

PMID- 16404250
TI  - Revisiting upper eyelid anatomy: introduction of the septal extension.
AB  - BACKGROUND: The current trend in plastic surgery of the eyelid has taken on
      increased dependence on anatomical considerations in the marriage of aesthetic
      and functional ideals. Often, the plastic surgeon performs ptosis and/or septal
      surgery in conjunction with blepharoplasty. The relationship between eyelid
      adnexal structures and upper eyelid function is a delicate but critical one.
      Current anatomical description states that the septum does not reach the superior
      tarsal border and inserts at a variable level on the levator aponeurosis.
      Conflicting observations in clinical practice stimulated this study to delineate
      the septal relationship to surrounding structures. In addition, this study may
      help to explain the increased rate of recurrence in ptosis repairs that
      incorporate plication techniques. METHODS: Dissection of four fresh cadaveric
      upper lid specimens in situ along with hematoxylin and eosin and trichrome stains
      of harvested eyelid tissue were used to redefine septal anatomy. Clinical case
      correlations are made to illustrate the significance of the histologic findings.
      RESULTS: A distinct septal extension was demonstrated arising from the orbital
      septum and covering preaponeurotic fat and tarsus completely. Histology of the
      anterior lamellae confirmed the presence of this thin fibrous sheet. In vivo
      assessment of this structure verifies its dynamic role in upper lid function. The
      clinical ramifications of this anatomical nuance are realized. CONCLUSIONS: A
      septal extension to the ciliary margin of the upper eyelid is established. Suture
      plication of the septal extension can induce lid elevation, with potential
      postoperative lid retraction. Intraoperative failure to recognize and distinguish
      this extension from the aponeurosis proper may lead to the high reported rates of
      unsuccessful ptosis correction. This refinement of septal anatomy should increase
      precision and help surgeons avoid complications in advanced blepharoplasty and
      ptosis surgery.

PMID- 16404252
TI  - Effect of augmentation mammaplasty on breast sensation.
AB  - BACKGROUND: Studies of alterations in breast sensibility after augmentation
      mammaplasty have produced conflicting results. Such discrepancies may be
      attributed to unsophisticated measuring devices used in earlier studies leading
      to less accurate measurements and to the comparison of results to different
      surgical techniques. The primary purpose of our study was to conduct a
      prospective clinical trial to quantify specific sensory outcomes before and after
      submuscular breast augmentation. METHODS: Preoperative and postoperative
      questionnaires were used to assess patients' subjective observations on breast
      sensation. Quantitative data were collected using a very accurate device, the
      Pressure-Specified Sensory Device, to assess objective breast sensation. Thirty
      three micromastia patients underwent quantitative measurements preoperatively
      (baseline), at 2 to 4 weeks and 6 months postoperatively to assess breast
      sensitivity. RESULTS: The quantitative data showed similar patterns of sensory
      change between both the periareolar and the inframammary surgical approach over
      time. The inferior region was the only region that showed a diminished
      sensitivity threshold of 9.5 +/- 2.9 gm/mm2 for the inframammary incision, a
      significantly poorer average than the periareolar incision of 1.7 +/- 0.6 gm/mm2
      with p = 0.008 at 6 months. Older patients had significantly higher thresholds of
      sensitivity compared with younger patients (p < 0.02). CONCLUSIONS: Our study
      suggests that the periareolar incision may produce less sensory loss in the lower
      pole of the breast when compared with the inframammary incision. The outcome of
      this study provides both the surgeon and the patient with concrete information
      regarding mammary sensation after augmentation mammaplasty and leads to a better
      informed-consent process.

PMID- 16404254
TI  - Fascial suspension mastopexy.
AB  - BACKGROUND: The objective of this study was to assess a new procedure for breast
      mastopexy, fascial suspension mastopexy. METHODS: Between December of 2001 and
      July of 2004, 52 patients (102 breasts) underwent fascial suspension mastopexy.
      Sixteen women had grade 1 ptosis (30 percent), 31 had grade 2 ptosis (60
      percent), two had grade 3 ptosis (4 percent), two (4 percent) had breast
      asymmetry and underwent unilateral mastopexy, and one had pseudoptosis (2
      percent). Of the 52 patients, 43 (83 percent) underwent fascial suspension
      mastopexy only, whereas nine patients (17 percent) underwent fascial suspension
      mastopexy combined with breast parenchymal excision of less than 120 g in each
      breast. Three patients (6 percent) underwent combined procedures. RESULTS: The
      complication rate was 7.7 percent (four patients). Two patients underwent
      conversion of the vertical scar into a horizontal scar. One patient underwent
      drainage of a hematoma 1 day after her operation, and one patient developed a
      hypertrophic scar. The average follow-up was 1.4 years, with the longest follow
      up being 3.5 years. On a scale of 1 (very poor) to 10 (excellent), postoperative
      ptosis correction was rated as 8.8, breast symmetry as 8.4, postoperative upper
      pole fullness as 9.1, postoperative medial breast fullness as 7.8, and overall
      breast shape and contour as 8.6. CONCLUSIONS: Fascial suspension mastopexy is
      safe, simple, and versatile; does not require pectoralis major flap harvesting;
      and achieves an excellent suspension of breast parenchyma, creating a projected
      and rejuvenated breast shape with upper pole fullness and long-standing breast
      contour.

PMID- 16404255
TI  - The importance of the retaining ligamentous attachments of the forehead for
      selective eyebrow reshaping and forehead rejuvenation.
AB  - BACKGROUND: Forehead rejuvenation procedures can lead to excessive elevation of
      the medial brow, resulting in the "surprised look." Differential treatment of the
      medial and lateral brow allows more precise positioning. The purpose of this
      study was to determine whether retaining structures exist in the forehead that
      would permit this differential elevation. METHODS: Anatomical dissections were
      performed in the foreheads of 12 cadavers. Multiplanar dissections at the
      subperiosteal, subgaleal, and subcutaneous levels were performed on eight
      hemiforeheads. Clinical correlation for these findings was obtained during
      endoscopic and open brow-lift surgery. RESULTS: Four retaining structures of the
      brow were identified: three medial and one lateral. The superomedial attachment
      begins 13 mm from the midline and 10.8 mm above the supraorbital rim. The
      superolateral attachment begins 23 mm from the midline and 10.3 mm above the
      supraorbital rim. The inferomedial attachment begins 12.6 mm from the midline at
      the level of the supraorbital rim, just medial to the supraorbital nerve. These
      three structures were found to control the position of the medial brow.
      Laterally, brow position was controlled by a broad ligamentous attachment
      extending across the lateral aspect of the supraorbital rim. CONCLUSIONS: Medial
      retaining structures have been found to extend from the cranium into the forehead
      musculature. Release of the lateral broad ligamentous attachment was performed,
      followed by selective preservation of medial retaining structures. With this
      approach, we were able to gain control of the position of the medial brow and
      prevent overelevation and lateral spreading.

PMID- 16404256
TI  - Survival of diced cartilage grafts: an experimental study.
AB  - BACKGROUND: Use of diced cartilage grafts in rhinoplasty surgery has recently
      undergone a dramatic resurgence. Some authors recommend wrapping diced cartilage
      with oxidized methylcellulose (i.e., Surgicel). Others prefer wrapping diced
      cartilage with autogenous deep temporal fascia. This study was designed to
      compare the behavior of diced cartilage grafts as an isolated entity or when
      wrapped with either Surgicel or deep temporal fascia. METHODS: Septal cartilage
      and deep temporal fascia were obtained from five patients in this institutional
      review board-approved study. The cartilage was diced into 0.5-mm pieces and
      implanted into subcutaneous dorsal skin pockets of Rowlett nude rats as isolated
      diced cartilage grafts, or wrapped in Surgicel or deep temporal fascia. Pieces of
      Surgicel and fascia were implanted alone as controls. The specimens were
      harvested at 8 weeks; processed by thin-section histology; stained with
      hematoxylin and eosin, Masson's trichrome, glial fibrillary acidic protein,
      safranin-O, and Evans van Gieson; and evaluated to determine cartilage viability
      and architectural characteristics. RESULTS: Diced cartilage wrapped in Surgicel
      yielded the lowest percentage viability and minimal staining with hematoxylin and
      eosin, trichrome tissue, safranin-O, and Evans van Gieson stains. Diced cartilage
      grafts wrapped in fascia had the greatest percentage of viable cartilage. The
      grafts wrapped in deep temporal fascia also demonstrated the strongest staining
      with the aforementioned stains. Differences in uptake of glial fibrillary acidic
      protein were not noticeable between the three groups. However, absolute numbers
      of nucleated lacunae and basophilic lacunae were significantly higher for grafts
      wrapped in deep temporal fascia. CONCLUSIONS: Diced cartilage grafts have
      reemerged as a viable method for nasal reconstruction in both primary and
      secondary rhinoplasty. Wrapping diced cartilage specimens contains the individual
      pieces and facilitates graft placement. Surgicel wraps appear to incite an
      inflammatory response and subsequent absorption of the cartilage. Fascia wraps
      appear to minimize inflammatory responses to the cartilage, thereby preserving
      healthy cartilage. This study demonstrates that deep temporal fascia is the
      preferred envelope with which to facilitate graft containment and maintain
      chondrocyte viability of diced cartilage grafts.

PMID- 16404257
TI  - Vascularized tissue-engineered ears.
AB  - BACKGROUND: A paucity of appropriate regional and local matching tissue can
      compromise the reconstruction efforts in areas of the body that require
      specialized tissue. The current study uses techniques of vascular prefabrication,
      tissue culturing, and capsule formation to form a vascularized ear construct that
      is reliably transferable on its blood supply. METHODS: Thirty male Wistar rats
      (250 to 350 g) were anaesthetized. An incision was made over the right lower
      abdominal wall. A pocket was formed by blunt dissection just below the panniculus
      carnosus. A separate incision was made over the right femoral vessels, which were
      then isolated and transected distally. The vessels were transposed in a
      subcutaneous plane to the abdominal wound. A silicone mold in the shape of an ear
      (2 x 1.5 cm) was placed over the transposed vessels in the abdominal wound
      pocket. The wounds were closed. Auricular cartilage was minced, washed, and
      cultured. After 14 days, the chondrocyte culturing was complete and a
      vascularized capsule based on the incorporated, transposed femoral vessels was
      formed. The abdominal incision was then reopened, an incision was made in the
      lateral capsule, and the cultured chondrocytes were introduced into the molded
      capsule. Study groups included capsules filled with chondrocytes only,
      chondrocytes and a fibrin glue carrier, and the fibrin glue only. The capsule was
      closed and the wounds sutured. The prefabricated, prelaminated construct was
      isolated on its vascular pedicle 14 days later and traversed microsurgically to
      the contralateral leg vessels. Histologic analysis was performed. RESULTS: All 30
      capsules were completely vascularized and could be reliably isolated and
      transferred microsurgically on the transposed femoral vessels. The pedicle, being
      incorporated directly into the capsule, provided the dominant blood supply to the
      construct. None of the capsules with the fibrin glue only retained any shape and
      all were devoid of cartilage. Similarly, there was no evidence of retained
      cartilage in the capsules filled with chondrocytes alone. All capsules with the
      chondrocytes and the fibrin carrier had mature shaped cartilage preserved.
      External molds were required to maintain the shape of the ear. Extrusion,
      although almost uniform in the group with external molds, did not interfere with
      the end construct shape or vascularity. When molds were used, four of six had
      excellent maintenances of shape and two of six had only minor superior pole
      deformation. All constructs were reliably transferred as free flaps. CONCLUSIONS:
      The authors have shown that transposing a vascular pedicle to a subcutaneously
      placed silicone block will result in a vascular capsule that can be mobilized and
      transferred based solely on the pedicle. Although the capsule provides
      vascularity to the chondrocytes, the cultured cartilage will fill the shape of
      the silicone mold only if an appropriate carrier such as fibrin glue is used and
      an external mold is applied.

PMID- 16404258
TI  - Engineering a composite neotrachea in a rat model.
AB  - BACKGROUND: Attempts to reconstruct the trachea have been largely unsuccessful
      because of its rigidity and opening to the outside environment. Materials that
      impart rigidity are usually alloplastic, so they cannot be exposed to the open
      environment without an unacceptably high risk of infection and rejection. The
      authors hypothesized that tissue engineering principles can be employed to
      construct a well-integrated neotrachea with rigid support and an epithelial
      lining to mimic the structure and function of the native trachea. METHODS: A 30
      mm-long segment of polytetrafluoroethylene vascular graft with a diameter of 10
      mm was lined with a fascial flap based on the superficial inferior epigastric
      artery with full-thickness skin grafts on its luminal surface. The composite unit
      was then buried under the abdominal skin of 20 rats and harvested 3 weeks later.
      Microfil and methylene blue dye were injected into the superficial inferior
      epigastric arteries and histologic analyses were performed to assess
      microcirculation and polytetrafluoroethylene-tissue integration. RESULTS: Two
      composite neotracheas experienced minor damage due to chewing by the rats, but
      all other neotracheas were viable and without infection. Injection studies
      demonstrated excellent circulation throughout the fascial flaps and skin grafts
      and across the polytetrafluoroethylene grafts to the overlying abdominal skin.
      Histologic analyses revealed abundant muscle-walled blood vessel ingrowth within
      the polytetrafluoroethylene grafts and all layers of the neotracheas with minimal
      inflammatory reactions. CONCLUSION: The authors successfully have engineered a
      well-integrated neotrachea in rats that possesses rigid support, an epithelial
      lining, and reliable coverage-the prerequisites for successful trachea
      reconstruction.

PMID- 16404259
TI  - PDGF gene therapy enhances expression of VEGF and bFGF genes and activates the NF
      kappaB gene in signal pathways in ischemic flaps.
AB  - BACKGROUND: Gene therapy is a novel approach for enhancing the viability of
      ischemic flaps. Expression of growth factor genes pertinent to angiogenesis and
      activation of genes of relevant signal pathways are imperative for improving flap
      viability. The authors investigated the gene expression profiles of growth
      factors and signal transduction pathways in ischemic flaps after PDGF gene
      therapy. METHODS: Twenty Sprague-Dawley rats were divided into two groups. The
      experimental group (n = 10) received the plasmid vector containing the PDGF cDNA
      injected into the dermis of the flap area, whereas the control group (n = 10)
      received the physiologic saline. Seven days later, a dorsal random flap was
      raised. Seven days after surgery, flap viability was assessed, and expression of
      VEGF, bFGF, TGF-beta1, NF-kappaB, Erk2, Stat1, and Smad2 genes of the NF-kappaB,
      MAPK, JAK-STAT, and Smad pathways was assessed by quantitative analysis of the
      products of reverse-transcriptase polymerase chain reaction. RESULTS: Transfer of
      exogenous PDGF gene significantly improved flap viability (p = 0.011). Levels of
      expression of VEGF and bFGF genes in the flap were significantly elevated after
      PDGF gene transfer (p = 0.0001 and p = 0.001, respectively). Expression of the NF
      kappaB gene was significantly elevated (p = 0.041). In contrast, expression of
      TGF-beta1, and Erk2, Stat1, and Smad2 genes was not changed. CONCLUSIONS:
      Transfer of exogenous PDGF gene to ischemic flaps promotes expression of VEGF and
      bFGF genes and activation of NF-kappaB gene in addition to its effects on the
      PDGF gene. The finding implies that transfer of the gene of one growth factor
      ultimately improves the expression of the genes of multiple growth factors.
      Activation of the NF-kappaB gene suggests that the NF-kappaB pathway may be
      important in enhancement of flap viability and will likely be a target of future
      efforts of regulation of signaling process in treatment of ischemic flaps.

PMID- 16404261
TI  - Quantification of total and perfused blood vessels in murine skin autografts
      using a fluorescent double-labeling technique.
AB  - BACKGROUND: Two theories exist regarding the revascularization of skin
      autografts: direct anastomosis between graft vessels and bed vessels, and
      ingrowth of bed vessels (angiogenesis) into the graft. This study characterizes
      revascularization, spatially and chronologically, in a murine skin autograft
      model using a double-labeling technique. METHODS: Full-thickness (1 cm2) skin
      grafts were performed on adult male C57/Bl6 mice. After 48 hours, 60 hours, 3
      days, 5 days, and 14 days (n = 3 mice per time point) terminal intracardiac
      perfusion with a fluorescein/dextran dye demonstrated vascular filling of graft
      blood vessels. Fluorescence immunohistochemistry of CD31+ endothelial cells
      allowed counting of total vessels and fluorescein perfusion quantification of
      patent vessels in the lateral graft area, central graft area, graft bed, and
      wound margins. RESULTS: Initial filling of graft vessels was seen after 48 hours.
      This included vessels in the papillary dermis of the graft, and there was no
      significant difference in the percentage of filled vessels in the deep dermis of
      the graft compared with the papillary dermis of the graft. A rapid increase in
      vessel filling was seen between 48 and 60 hours in all areas of the graft. Vessel
      filling occurred mainly in the central area of the graft rather than in the
      lateral areas. CONCLUSIONS: The short time course of vessel filling indicates
      that the initial onset of revascularization is attributable to early anastomoses
      between graft and bed vessels, mainly in the central area of the graft. These
      findings have implications for both autograft revascularization in a clinical
      setting and in the development of tissue-engineered skin substitutes.

PMID- 16404262
TI  - Early excision of a full-thickness burn prevents peripheral nerve conduction
      deficits in mice.
AB  - BACKGROUND: A full-thickness 20 percent body surface area burn in mice produces a
      significant decrease in tibial motor nerve conduction velocity within 6 hours of
      the burn and in sensory conduction velocity within 7 days. This suggests that
      cutaneous burn injury produces a systemic response that affects peripheral motor
      and sensory nerve function at a distance from the burn site. The authors tested
      the hypothesis that burn wound excision either 30 minutes or 3 hours after burn
      would prevent neuropathy. METHODS: A 20 percent body surface area third-degree
      burn was applied to the backs of anesthetized mice using procedures that followed
      National Institutes of Health guidelines. Motor nerve conduction velocity and
      sensory conduction velocity were determined in intact, anesthetized mice by
      percutaneous nerve stimulation. Burn wounds were excised and closed at 30 minutes
      or 3 hours after burn. Motor nerve conduction velocity and sensory conduction
      velocity were measured before burn and 1, 3, 7, 14, and 21 days after a burn or
      sham procedure. The number of circulating neutrophils and serum concentrations of
      tumor necrosis factor-alpha, nitrite, and electrolytes were also determined in
      each group. RESULTS: Motor nerve conduction velocity and sensory conduction
      velocity in the 30-minute excision (n = 10) and sham group (n = 5) were not
      significantly different. Motor nerve conduction velocity and sensory conduction
      velocity in the nonexcised group (n = 10) and 3-hour excision group (n = 10) were
      significantly decreased. Serum tumor necrosis factor-alpha concentration was
      elevated 6 hours after burn in nonexcised animals (n = 9) and in 3-hour excision
      mice (n = 8) but was not significantly different in the sham (n = 8) and the 30
      minute excision group (n = 7). CONCLUSION: The authors conclude that burn wound
      excision at 30 minutes but not at 3 hours prevents the nerve conduction deficits
      measured in mice with 20 percent body surface area burns. The cellular basis of
      burn-induced neuropathy is unknown, but nitric oxide and tumor necrosis factor
      alpha-alpha appear to play a role.

PMID- 16404263
TI  - Observation of the relationship between the shape of skeletal muscles and their
      nerve distribution patterns: a transparent and microanatomic study.
AB  - BACKGROUND: There are many gaps in the understanding of the neuroanatomy of
      skeletal muscles with regards to the nerve distribution pattern and shape of the
      muscles. This study was designed to examine the entire intramuscular nerve
      distribution patterns of various human skeletal muscles. METHODS: The
      relationships among nine skeletal muscles with various architecture (rhomboid
      major, biceps brachii, flexor pollicis longus, rectus femoris, sternohyoid,
      trapezius, masseter, digastric muscles) and their nerve-distribution patterns
      were investigated in four fetal cadavers using the Sihler staining method. The
      diameter and number of extramuscular (main) and major nerve branches, the number
      of minor nerve branches, and anastomoses were examined and evaluated
      statistically. RESULTS: With regards to the number of extramuscular (main) nerve
      branches, the rhomboid major muscle resembled the flexor pollicis longus,
      trapezius, masseter, and sternohyoid muscles, and the anterior belly of the
      digastricus muscle (p > 0.05), whereas it was significantly different from the
      rectus femoris, the posterior belly of digastricus, and the long and short heads
      of the biceps brachii (p < 0.05). Trapezius and masseter muscles were different
      from all of the skeletal muscles that were studied with regards to the diameter
      of main branches (p < 0.05). The masseter muscle had the largest diameter (p <
      0.05). With regards to the number of minor nerve branches, the sternohyoid muscle
      was significantly different from all the skeletal muscles that were studied (p <
      0.05) except the short head of the biceps brachii, rectus femoris, and the
      posterior belly of digastricus (p > 0.05). As for the number of neural
      anastomoses, the sternohyoid muscle was statistically different from all skeletal
      muscles that were studied (p < 0.05) except the masseter and trapezius muscles (p
      > 0.005). CONCLUSIONS: A surgeon's thorough knowledge of the relationship between
      the shape and nerve distribution pattern of skeletal muscles is important in
      successful reinnervation and regeneration of these muscles. It might also be
      useful in the field of muscle transplantation.

PMID- 16404264
TI  - Endoscopic carpal tunnel release: a review of 753 cases in 486 patients.
AB  - BACKGROUND: Endoscopic carpal tunnel release is gaining increasing acceptance
      relative to the standard open carpal tunnel release for the treatment of carpal
      tunnel syndrome. Concerns about endoscopic carpal tunnel release include
      effectiveness of therapy and complication rates. This study attempted to evaluate
      outcomes of endoscopic carpal tunnel release in a large patient cohort. METHODS:
      Four hundred eighty-six patients (753 hands) with carpal tunnel syndrome who
      underwent endoscopic carpal tunnel release by a single surgeon were reviewed
      retrospectively. Data included demographics, subjective complaints, prior
      interventions, preoperative examination findings, and postoperative follow-up.
      All follow-up data were obtained from a single, independent, occupational therapy
      clinic. RESULTS: Median patient age was 48 years. Three hundred seventy-seven
      patients were gainfully employed at presentation, and 206 filed a worker's
      compensation claim. Median symptom duration was 2 years. Nonoperative therapy was
      ineffective in 151 patients. Preoperative nerve conduction studies were
      consistent with carpal tunnel syndrome in 472 patients (97 percent); all patients
      had either physical examination findings or nerve conduction studies consistent
      with carpal tunnel syndrome. Four hundred eighty-six patients (100 percent)
      obtained symptom relief. Complications included one transient median nerve
      neurapraxia, six complaints of residual pain, and one complaint of
      hypersensitivity. Worker's compensation patients and non-worker's compensation
      patients returned to work full-duty at similar times postoperatively. Ninety
      percent of employed patients returned to their original occupation. CONCLUSIONS:
      The authors' data indicate that an endoscopic approach for the treatment of
      carpal tunnel syndrome is safe and effective. Patients demonstrated a high return
      to-work rate and an extremely low complication rate. The data challenge the
      belief that endoscopic carpal tunnel release results in higher complication
      rates.

PMID- 16404265
TI  - Long-term follow-up of high-pressure injection injuries to the hand.
AB  - BACKGROUND: High-pressure injection injury is an injury caused by accidental
      injection of substances by industrial equipment. This injury may have devastating
      sequelae. The goal of this study was to assess the long-term outcome of high
      pressure injection injury to the hand. METHODS: In this historical prospective
      study, patients who had previously sustained high-pressure injection injury were
      examined. Assessment included measurement of grip and pinch strength, range of
      motion, two-point discrimination, and use of a questionnaire regarding present
      complaints and return to the work force. RESULTS: Twenty-three patients were
      examined. Follow-up length was on average 8.5 years. The injured hand was most
      often (43 percent) the right dominant hand, the index in 65 percent, the thumb in
      25 percent, and other locations in 10 percent. Only 43 percent of patients
      returned to their previous employment. Patient complaints were, in descending
      frequency, cold intolerance, hypersensitivity, paresthesias, constant pain, and
      impairment of activities of daily living. Metacarpophalangeal range of motion was
      decreased on average by 8.1 percent (p = 0.019), proximal interphalangeal joint
      range of motion was decreased by 23.9 percent (p = 0.001), and distal
      interphalangeal range of motion was decreased by 29.7 percent (p= 0.018). Maximum
      grip was decreased compared with the expected grip by 12 percent (p = 0.023).
      Pinch was decreased by 35 percent (p < 0.001). Two-point discrimination was
      increased by 49 percent (p < 0.007). CONCLUSION: This study confirms the fact
      that high-pressure injection injury to the hand is a significant problem.
      Virtually all patients suffer sequelae of this injury. The injury has significant
      repercussions for future function and reintegration into the work force.

PMID- 16404266
TI  - Cranial vault distraction: its illusionary effect and limitation.
AB  - BACKGROUND: Distraction osteogenesis has some advantages, such as less hazardous
      complications, less scarring, and fewer bone defects. However, it has not been
      fully accepted yet because of a unidirectional expansion along the distraction
      device. Because cranial expansion is limited by scalp tension and soft-tissue
      scarring, undercorrection of the cranium and relapse of the vault deformities
      have occasionally been seen on long-term follow-up. These patients also had so
      much bone defect that the donor bone was inadequate for immediate revisions, and
      dissection under the scalp was complicated. METHODS: The authors used distraction
      osteogenesis to treat 12 cases of craniosynostosis. Five patients were syndromic
      (two cases of Pfeiffer's syndrome, two cases of Crouzon's disease, and one case
      of Apert's syndrome), and seven were nonsyndromic (four cases of brachycephaly,
      two cases of scaphocephaly, and one case of plagiocephaly). RESULTS: After only
      unidirectional expansion without vertical reduction, the shape of the cranium was
      satisfactorily improved, which might have been an illusion caused by the relative
      reduction attributed to the elongation by the distraction osteogenesis and, in
      brachycephaly, alteration of the patient's head position resulting from
      inclination of the facial plane by forehead advancement. However, in
      scaphocephaly, the unique deformity in the occipital and frontal regions remained
      after simple distraction. Distraction osteogenesis should be applied for a narrow
      cranium because the bone defect and scalp closure could pose problems. Radical
      reshaping should be used in cases of sufficient donor bone and scalp closure.
      Although additional surgery is unavoidable for device removal, minor revisions
      can be performed for revision of the irregularity at that time. CONCLUSION:
      Except for prolonged treatment, based on minimally invasive operations,
      distraction cranioplasty might be applied extensively in cases of
      craniosynostosis.

PMID- 16404268
TI  - Cranioplasty with subcutaneously preserved autologous bone grafts.
AB  - BACKGROUND: The efficacy of reconstructing a cranial defect with the craniectomy
      bone graft (bone flap) banked in a subcutaneous pocket of the abdominal wall
      after emergency decompressive craniotomy was evaluated. METHODS: A retrospective
      study was performed on 53 of 65 consecutive patients who underwent emergency
      decompressive craniectomy and bone graft placement in the abdominal wall and
      survived to graft replacement. Clinical outcome after graft replacement was
      determined by the adequacy of the recovered craniectomy graft to achieve
      satisfactory reconstruction, the incidence of infection and the need for
      revisional surgery. RESULTS: Forty-nine of the 53 patients (92 percent) in whom
      delayed autogenous graft replacement was attempted achieved a satisfactory one
      stage reconstruction. In 42 of these 49 patients, autogenous graft replacement
      alone was performed. In eight patients it was necessary to supplement the graft
      with alloplastic material to achieve desired contour. One patient who underwent
      reconstruction with the autogenous bone graft alone, underwent late revision
      cranioplasty to improve contour. There were three infections. One graft was found
      infected in the abdominal pocket at retrieval. Two were lost to operative
      infection after graft replacement. Histology of two stored grafts performed after
      abdominal pocket retrieval demonstrated a mixture of necrotic and newly formed
      woven bone. A bone scan performed 1 year after graft replacement showed
      radionuclide activity of the graft almost identical to that of intact neighboring
      bone. CONCLUSIONS: Subcutaneous storage preserves viability of portions of
      autogenous bone grafts. Cranioplasty performed with a subcutaneously preserved
      craniectomy graft has a low revision rate.

PMID- 16404269
TI  - Neurodevelopmental delays in children with deformational plagiocephaly.
AB  - BACKGROUND: The purpose of this study was to determine whether, in fact, infants
      with deformational plagiocephaly, or plagiocephaly without synostosis,
      demonstrated cognitive and psychomotor developmental delays when compared with a
      standardized population. Through this study, we chose to expand upon our earlier
      findings from 2001 on patients with deformational plagiocephaly. METHODS: The
      study population includes a total of 110 consecutive patients, prospectively
      followed then retrospectively reviewed. Each infant was assessed using the Bayley
      Scales of Infant Development-II scoring system. The developmental analysis was
      categorized as either mental or psychomotor using the mental developmental index
      or the psychomotor developmental index, respectively. These infants were
      subcategorized into four groups: accelerated, normal, mild, or severely delayed.
      The groups were then compared with a standardized Bayley's age-matched
      population, using chi-square test goodness-of-fit tests. RESULTS: Infants with
      deformational plagiocephaly were found to have significantly different
      psychomotor development indexes and mental developmental indexes when compared
      with the standardized population (p < 0.0001; p < 0.0001). With regards to the
      mental developmental index scores, none of the infants with deformational
      plagiocephaly were accelerated, 90 percent were normal, 7 percent were mildly
      delayed, and 3 percent were severely delayed. With regards to the psychomotor
      development index scores, none of infants were accelerated, 74 percent were
      normal, 19 percent were mildly delayed, and 7 percent were severely delayed.
      CONCLUSIONS: This study indicates that before any intervention, infants with
      deformational plagiocephaly show significant delays in both mental and
      psychomotor development. Also of particular note is that no child with
      deformational plagiocephaly showed accelerated development.

PMID- 16404271
TI  - Intralesional bleomycin for the treatment of hemangiomas.
AB  - BACKGROUND: Hemangiomas, although often small at birth, enter a proliferative
      phase in which growth may be rapid and unpredictable. Furthermore, involution
      often takes many years, with attendant psychological sequelae to the child. This
      is aggravated by the fact that most hemangiomas affect the head and neck and are
      visible and difficult to conceal. METHODS: Thirty children (five boys and 25
      girls) were treated at a pediatric teaching hospital during an 18-month period
      with a protocol of intralesional bleomycin, 0.3 to 0.6 mg/kg (per dose),
      administered under general anesthesia. The lesions were measured and photographed
      serially. Complications were also recorded. RESULTS: The mean age of the children
      was 20 months (range, 3 months to 8 years) and the mean number of injections
      given was five (range, three to eight). The mean total dose administered was 13.6
      mg (range, 1.4 to 25 mg). Outcome was assessed by a panel of five plastic
      surgeons. Twenty-two children were assessed as achieving a response of greater
      than 75 percent reduction in the size of the hemangioma (of which 10 children
      were assessed as having total involution >90 percent response). In seven
      children, there was a 50 to 75 percent reduction in size of the hemangiomas, and
      one child was judged to have a 25 to 50 percent reduction in size of the
      hemangioma. Hyperpigmentation was the most common complication, and occurred in
      13 children. The mean follow-up period was 14 months (range, 3 to 35 months).
      CONCLUSIONS: Intralesional bleomycin is another method with which to treat
      hemangiomas in children and may be particularly helpful for large hemangiomas of
      the head and neck. Repeated general anesthetics are required, and scarring with
      hyperpigmentation may occur.

PMID- 16404272
TI  - Evidence of significant sternocleidomastoid atrophy following modified radical
      neck dissection type III.
AB  - BACKGROUND: Although modified radical neck dissection type III preserves the
      spinal accessory nerve, the internal jugular vein, and the sternocleidomastoid
      muscle, the authors believe there is a significant morbidity to retained
      structures after neck dissection. Although the effects on accessory nerve
      function and internal jugular vein patency have been documented, there is little
      information about sternocleidomastoid morphology and function following modified
      dissection. METHODS: Using a SonoSite ultrasound machine, the authors assessed
      sternocleidomastoid muscle morphology, at rest and during contraction, in a
      cohort of 45 patients who underwent modified radical neck dissection type III
      with no radiotherapy. All patients had head and neck cancers and received
      unilateral neck dissection as part of their primary treatment. Static and dynamic
      measurements were performed at three different levels of the muscle, with the
      neck in the neutral position. The contralateral neck of the same patient was used
      as a control. Local muscle asymmetry patterns were calculated using the Absolute
      Asymmetry Index. RESULTS: Significant sternocleidomastoid atrophy was noted on
      the side of modified radical neck dissection type III (p < 0.05). The atrophy was
      particularly marked in the caudal and middle portions of the sternocleidomastoid
      muscle and was likely related to damage to the segmental blood supply in the
      caudal and middle portions of the muscle as well as injury to the innervation.
      CONCLUSION: Despite evidence of significant atrophy, the muscle still underwent
      morphological changes during contraction that were comparable to those on the
      normal control side.

PMID- 16404273
TI  - How to make the blockage between the nasal cavity and intracranial space using a
      four-layer sealing technique.
AB  - BACKGROUND: Craniofacial surgery for facial advancement or correction of severe
      craniofacial malformations such as orbital hypertelorism, Crouzon's disease, and
      Apert's syndrome may carry great risk. Postoperative infection after craniofacial
      surgery is a life-threatening complication. Ascending infection via nasofrontal
      communication in frontofacial monobloc advancement, intracranial Le Fort III
      osteotomy, correction of hypertelorism (intracranial approach), and acute trauma
      of cribriform plate can lead to life-threatening meningitis and
      meningoencephalitis. METHODS: A four-layer sealing technique for the closure of
      nasofrontal communication using Gelfoam, galeopericranial flap, rib bone graft,
      and Tissel is a very effective method. Until the rib bone graft is taken up,
      Gelfoam is used to temporarily block bony defects and prevents displacement of
      the rib bone graft. The authors used galeoperiosteal flap for the sufficient
      blood supply to the rib bone graft. Tissel is used as a biologic adhesive and for
      blockage of the surrounding gaps. RESULTS: There were no cases of cerebrospinal
      fluid rhinorrhea, epidural abscesses due to nasofrontal ascending infection, or
      meningitis, and no cases underwent debridement due to necrosis of the frontal
      bone flap. This indicated that the blockage of nasofrontal communication was
      successful in this series. Moreover, postoperative cosmetic outcomes were
      satisfactory. CONCLUSION: This study indicated that the blockage using the
      Gelfoam, galeopericranial flap, rib bone graft, and Tissel application was
      effective for the thorough management of nasofrontal fistula and the prevention
      of recurrent episodes.

PMID- 16404274
TI  - Lower eyelid orbicularis oculi musculocutaneous flap for reconstruction of nasal
      tip and supratip defects.
AB  - BACKGROUND: In clinical practice, there are many ways to reconstruct nasal
      defects. Despite this fact, achieving a desirable image and better functional
      results is still a problem. Banner, bilobed, and dorsal nasal flaps have recently
      been used to reconstruct defects up to 2 cm. For defects larger than 2 cm, flaps
      raised from the frontal region and face are used. The major disadvantages of
      these flaps are the visible scar and the frequent need for a second session.
      METHODS: The authors used orbicularis oculi musculocutaneous flaps raised from
      the lower eyelid, containing branches of the angular artery and the infraorbital
      artery in its pedicle, to reconstruct nasal tip and supratip defects. Between
      February of 2002 and March of 2004, reconstruction with orbicularis oculi
      musculocutaneous island flaps raised from the lower eyelid was performed on 15
      patients (eight men and seven women) with nasal tip and supratip defects.
      Thirteen defects were secondary to basal cell carcinoma and two were secondary to
      congenital melanocytic nevus. The diameter of the defects ranged between 2.1 and
      3.1 cm (average diameter, 2.5 cm). Patients were between 25 and 72 years old
      (average age, 52 years). RESULTS: Patients were followed up for an average period
      of 6 months (range, 1 to 12 months). In two patients (13.3 percent),
      postoperative venous problems were seen but resolved in 3 days. Partial necrosis
      developed in one patient (6.6 percent). In one patient (6.6 percent), minimal
      scleral show was seen in tolerable ranges. Neither ectropion nor other eyelid
      deformities were seen. CONCLUSIONS: The authors believe that this flap is a good
      alternative for reconstruction of nasal defects because of its advantages,
      namely, the need for only a single session, minimal donor-site morbidity, better
      color and thickness match, and easy and faster surgery.

PMID- 16404275
TI  - Ineffective treatment of keloids with interferon alpha-2b.
AB  - BACKGROUND: Keloids are exuberant, disfiguring scars that result from an abnormal
      healing process. Current established treatment strategies include surgical
      resection, triamcinolone steroid injection, pressure therapy, silicone therapy,
      and radiotherapy. None of these therapies, either alone or in combination, offers
      consistent recurrence-free rates above 70 to 80 percent. The antiproliferative,
      antifibrotic cytokine, interferon alpha-2b, may be useful in keloid management
      because of its ability to interfere with collagen synthesis and fibroblast
      proliferation. METHODS: To determine the efficacy of interferon alpha-2b in
      keloid management, the authors prospectively evaluated the effects of interferon
      alpha-2b as postexcisional adjuvant therapy for keloids. Thirty-nine keloids in
      34 patients were photographed, measured, and surgically excised. The wound bed
      was injected twice with either interferon alpha-2b (treatment group; n = 13
      keloids) or triamcinolone (control group; n = 26 keloids) at surgery and 1 week
      later. The patients were followed up in the plastic surgery clinic. RESULTS: The
      trial protocol was terminated at midtrial surveillance. Among the 13 keloids that
      were treated with postoperative intralesional interferon alpha-2b, seven recurred
      (54 percent recurrence rate). In contrast, in the 26 keloids that received
      triamcinolone (control group), only four recurred (15 percent recurrence rate).
      Recurrence in either group did not correlate with location of the keloid or race.
      CONCLUSION: Interferon does not appear to be effective in the clinical management
      of keloids.

PMID- 16404276
TI  - Proximal vascular pedicle preservation for sartorius muscle flap transposition.
AB  - BACKGROUND: A variety of muscle flaps have been described to treat complex groin
      wounds associated with infected and/or exposed femoral vessels or vascular grafts
      and persistent lymphatic leaks, and for prophylaxis against wound breakdown
      following inguinal lymphadenectomy. The sartorius muscle flap has several
      advantages over other muscle flaps: it is immediately adjacent to the groin, it
      is easy to prepare, and the harvest causes no functional morbidity. Despite these
      advantages, the flap's reliability has been questioned because of the segmental
      blood supply to the muscle and the flap's limited arc of rotation. To improve the
      reliability of the flap, the authors defined the proximal vascular anatomy of the
      sartorius muscle in 20 human cadavers and assessed the correlation with 20
      clinical cases. They describe a technique for the harvest of the sartorius muscle
      transposition flap that preserves the most proximal pedicle. METHODS: From July
      of 2000 to January of 2004, 40 sartorius muscles were dissected in 20 human
      preserved cadavers. During the same time period, 21 sartorius muscle
      transposition flap procedures were performed in 19 patients for a variety of
      complex groin wound complications, including infection (n = 10), lymphadenectomy
      (n = 4), lymphatic leak (n = 3), exposed femoral vessels (n = 3), and high-risk
      wound (n = 1). The location of the most proximal vascular pedicle with respect to
      the anterior superior iliac spine was measured in each cadaveric dissection as
      well as in each clinical case. Outcomes were assessed in the clinical cases with
      respect to wound healing. RESULTS: The distance between the anterior superior
      iliac spine and the proximal vessels in the cadaver specimens was 6.6 +/- 1.3 cm
      (range, 5.0 to 9.5 cm). The distance between the anterior superior iliac spine
      and the proximal vessels in the clinical patients was 6.2 +/- 0.6 cm (range, 5.5
      to 7.5 cm). Patients were followed for an average period of 30 months (range, 5
      to 45 months). There were no incidences of partial or total flap necrosis. All
      wounds healed to completion. CONCLUSIONS: The proximal pedicle of the sartorius
      muscle is consistently located at 6.5 cm from the anterior superior iliac spine.
      Preservation of the proximal pedicle during dissection ensures the viability of
      the sartorius muscle transposition flap for the treatment of complex groin
      wounds.

PMID- 16404277
TI  - Long-term results of wounds closed under a significant amount of tension.
AB  - BACKGROUND: The authors present the long-term follow-up of scars on various
      locations up to 7 years postoperatively, after closure of large skin defects with
      the use of a skin-stretching device. METHODS: In a prospective, nonrandomized
      study of 30 patients whose initial wound could not be closed primarily without
      using a significant amount of tension, a complete follow-up of 24 cases was
      possible. Patients were observed preoperatively, postoperatively, and at long
      term follow-up (mean, 7 years) for wound control and scar evaluation. RESULTS: In
      28 cases (93 percent), successful closure of a large defect was achieved. In the
      other two cases, a split-thickness skin graft was needed for wound closure. With
      respect to long-term scar formation after 7 years (24 cases), scarring was
      observed mainly on the scalp (average, 56 percent), back (average, 52 percent),
      and shoulder (average, 53 percent). On the extremities, including thigh and
      groin, there was significantly less scarring (p = 0.0004; average, 10 percent).
      Three weeks after the operation, 23 percent of the total scar formation had
      already occurred, whereas 57 percent occurred by 3 months postoperatively and 83
      percent occurred by 6 months postoperatively. CONCLUSION: This study demonstrates
      the considerable difference in scar formation among scalp, back, and shoulder
      defects compared with those on the extremities, groin, and thigh.

PMID- 16404278
TI  - Reconstruction of chronic Achilles tendon defects with posterior tibial
      perforator flap and soleus tendon graft: clinical series.
AB  - BACKGROUND: Reconstruction of chronic composite defects of the Achilles region is
      difficult, and many techniques have been proposed, most of which are technically
      complex. A simple and effective technique has not yet been described. METHODS:
      Eight patients with chronic composite defects of the Achilles tendon underwent
      reconstruction using a local tendon graft from the soleus tendon and a posterior
      tibial perforator flap in a single stage. Follow-up was 9 to 50 months. RESULTS:
      All reconstructions were successful, without flap loss, infections, or reruptures
      of the tendon. Minor skin graft loss over the flap was a complication in three
      cases. Patient satisfaction was uniformly high. CONCLUSION: The posterior tibial
      perforator flap combined with a local tendon graft from the soleus tendon is an
      effective and technically simple solution for reconstruction of chronic infected
      defects of the Achilles tendon of moderate size.

PMID- 16404279
TI  - Distally based lateral and medial leg adipofascial flaps: need for caution with
      old, diabetic patients.
AB  - BACKGROUND: Reconstruction of defects around the ankle region has always been
      challenging for plastic surgeons. Distally based lateral and medial leg
      adipofascial flaps are among the flaps of choice for coverage of this difficult
      region. Presented here is the authors' clinical experience with these flaps,
      particularly emphasizing the complicated attempts in diabetic patients. METHODS:
      Seven skin defects around the ankle were reconstructed with lateral and medial
      leg adipofascial flaps. The lowermost perforators of the peroneal or posterior
      tibial artery were identified preoperatively, and a straight incision through
      skin only was made proximal to this perforator. With the skin flaps reflected,
      the adipofascial flap was than raised in the subfascial plane. The perforators to
      be retained in the base were located and the flap was then turned over to cover
      the defect, followed by application of a split-thickness skin graft over the
      flap. The donor site was closed primarily. RESULTS: The ages of the patients
      ranged from 25 to 80 years, and the size of the flaps ranged from 3 x 5 cm to 7 x
      10 cm. Four defects were reconstructed with lateral leg adipofascial flaps, and
      medial leg adipofascial flaps were used in three. Two flaps healed uneventfully.
      Partial or total graft loss and partial flap necrosis were observed in five
      patients, four of whom were diabetic. CONCLUSIONS: Leg adipofascial flaps offer a
      valuable option for repair of defects around the ankle in many cases. However,
      adipofascial flaps should be used with caution in old, diabetic patients and,
      when performed, the probability of a second or third procedure should be
      considered.

PMID- 16404280
TI  - Cost analysis of functional restoration surgery for extremity soft-tissue
      sarcoma.
AB  - BACKGROUND: Limb-sparing surgery, consisting of wide-margin tumor resection and
      preoperative or postoperative radiotherapy/chemotherapy, has become the surgical
      treatment of choice for extremity sarcomas. However, adequate tumor resection can
      sometimes compromise crucial limb function, necessitating functional restoration
      surgery. The purpose of this study was to determine the cost impact and
      functional outcomes of such procedures. METHODS: Patients receiving either
      functional restoration surgery or soft-tissue-only reconstruction following
      extremity soft-tissue sarcoma excision were identified. Patients were then
      compared along several dimensions: overall length of stay and its subdivisions,
      surgical time, and total charges and its subdivisions. Patients' functional
      outcomes were assessed with the Toronto Extremity Salvage Score. RESULTS: Sixty
      seven patients who underwent 69 limb-sparing procedures were identified. Fifteen
      of these procedures (eight upper extremity, seven lower extremity) required
      functional restoration surgery; 54 of these procedures (13 upper extremity, 41
      lower extremity) required only soft-tissue coverage. In the upper extremity,
      there was a statistically significant increase in overall length of stay (2.8
      days) and its subdivisions, surgical time (3.7 hours), and total charges (12,484
      dollars) and its subdivisions associated with performing functional restoration
      surgery. In lower extremity cases, statistically significant increases were
      determined in only the total charges (9190 dollars) and medical supply charges
      (13,204 dollars) following functional restoration. Patients who underwent
      functional restoration surgery had better postoperative function (mean Toronto
      Extremity Salvage Score, 82 versus 80), but this difference was not statistically
      significant. CONCLUSION: Although functional restoration surgery is more costly
      than soft-tissue reconstruction alone, the authors believe that the associated
      better functional outcome justifies its performance.

PMID- 16404281
TI  - Keloid pathogenesis and treatment.
AB  - BACKGROUND: Keloid management can be difficult and frustrating, and the
      mechanisms underlying keloid formation are only partially understood. METHODS:
      Using original and current literature in this field, this comprehensive review
      presents the major concepts of keloid pathogenesis and the treatment options
      stemming from them. RESULTS: Mechanisms for keloid formation include alterations
      in growth factors, collagen turnover, tension alignment, and genetic and
      immunologic contributions. Treatment strategies for keloids include established
      (e.g., surgery, steroid, radiation) and experimental (e.g., interferon, 5
      fluorouracil, retinoid) regimens. CONCLUSION: The scientific basis and empiric
      evidence supporting the use of various agents is presented. Combination therapy,
      using surgical excision followed by intradermal steroid or other adjuvant
      therapy, currently appears to be the most efficacious and safe current regimen
      for keloid management.

PMID- 16404282
TI  - Maternal cigarette smoking during pregnancy increases the risk of having a child
      with a congenital digital anomaly.
AB  - BACKGROUND: The U.S. Natality database from 2001 and 2002 was used to investigate
      the relationship between maternal cigarette smoking during pregnancy and the risk
      of having a child with polydactyly, syndactyly, or adactyly. METHODS: The records
      of 6,839,854 live births were examined to identify 5171 newborns with isolated
      polydactyly, syndactyly, or adactyly and 10,342 controls with no congenital
      anomalies. RESULTS: Maternal cigarette use during pregnancy was associated with a
      significantly elevated risk of having a child with a congenital digital anomaly
      (unadjusted odds ratio, 1.33; 95 percent confidence interval, 1.21 to 1.47; p <
      0.0001). Univariate analysis indicated that maternal marital status and medical
      risk factors (anemia, cardiac disease, lung disease, diabetes,
      hydramnios/oligohydramnios, pregnancy-associated hypertension, incompetent
      cervix, previous preterm or small-for-gestational-age infant, and rhesus factor
      sensitization) were potential confounding factors. After adjustment for these
      variables, the odds ratio remained significant (adjusted odds ratio, 1.31; 95
      percent confidence interval, 1.18 to 1.45; p < 0.0001). Cigarette consumption per
      day was divided into four groups: no smoking, 1 to 10 cigarettes per day, 11 to
      20 cigarettes per day, and 21 or more cigarettes per day. A statistically
      significant dose-response relationship was found when comparing each smoking
      category with the no-smoking reference group: 1.29 (95 percent confidence
      interval, 1.15 to 1.46), 1.38 (95 percent confidence interval, 1.12 to 1.71), and
      1.78 (95 percent confidence interval, 0.97 to 3.26), respectively. Increased
      cigarette smoking during pregnancy resulted in an elevated risk of having a child
      with polydactyly, syndactyly, or adactyly. CONCLUSIONS: This is the largest study
      to date to investigate specifically the association between maternal cigarette
      smoking and the risk of having a newborn with a congenital digital anomaly. The
      elevated odds ratio for tobacco use and the significant trend in the dose
      response relationship suggests smoking during pregnancy may be an important
      preventable risk factor for these common congenital differences.

PMID- 16404285
TI  - Omental flap coverage of Gore-Tex mesh: infections, milky spots, and abdominal
      wall "exit site" hernias.

PMID- 16404288
TI  - Defining the "gold standard" in breast reconstruction with abdominal tissue.

PMID- 16404286
TI  - Dissociative anesthesia for safety's sake.

PMID- 16404289
TI  - Use of the tracheal tube in isolated fractures of the zygomatic arch.

PMID- 16404291
TI  - Optimizing body contour in massive weight loss patients: the modified vertical
      abdominoplasty.

PMID- 16404292
TI  - Use of a grid to simplify botulinum toxin injection for axillary hyperhidrosis.

PMID- 16404293
TI  - Wishes and tissues: a concern about dimensional planning systems that lack volume
      restrictions and do not prioritize long-term soft-tissue coverage.

PMID- 16404294
TI  - Skin sensibility to pressure measured with a system of loads.

PMID- 16404295
TI  - Basal cell carcinoma and syringocystadenoma papilliferum arising in nevus
      sebaceus.

PMID- 16404297
TI  - Hydatid cyst of the scalp.

PMID- 16404296
TI  - A rare case of hypertrophic scar on the scalp.

PMID- 16404298
TI  - The "twist over": tie die?

PMID- 16404299
TI  - Misfortune during a blepharoplasty.

PMID- 16404300
TI  - Carving Gore-Tex reinforced sheets for augmentation rhinoplasty in Chinese
      patients.

PMID- 16404301
TI  - Rhinoplasty of a patient with congenital lacrimal fistula.

PMID- 16404302
TI  - Practical tips for otoplasty.

PMID- 16404303
TI  - Parotid duct repair by use of an embolectomy catheter with a microvascular clamp.

PMID- 16404304
TI  - Use of a window handle for postreduction protection of a fractured zygoma.

PMID- 16404305
TI  - The breast reduction and nipple reconstruction training models: real tissue
      training models.

PMID- 16404306
TI  - The graft said, "when I grow up, I want to be a flap": nipple reconstruction with
      the graft flap.

PMID- 16404307
TI  - A 1.8-kg keloid of the arm.

PMID- 16404308
TI  - A simple technique for umbilicus dilatation.

PMID- 16404309
TI  - Anaphylactic reaction to intralesional steroid injection.

PMID- 16404310
TI  - Liposuctionable fat: a hypothetic model.

PMID- 16404311
TI  - Accurate assessment of table and patient alignment for aesthetics.

PMID- 16404312
TI  - Use of Quixil human surgical sealant in achieving hemostasis on a skin graft
      recipient site of a fully heparinized patient.

PMID- 16404313
TI  - Manual graft meshing: taking it further.

PMID- 16404314
TI  - A novel use of Jelonet to facilitate the harvest of split-thickness skin grafts
      freehand.

PMID- 16404315
TI  - Easy continuous perioperative suction drainage during vascular anastomoses.

PMID- 16404316
TI  - Postpartum depression as a risk factor in unnecessary cosmetic surgery.

PMID- 16404317
TI  - Solution to a slippery problem in theater.

PMID- 16404318
TI  - Salvage of venous congested flaps by simple methods.

PMID- 16404319
TI  - Protection of microanastomoses: the "through-drain" transcutaneous anchor stitch.

PMID- 16404320
TI  - Healthy aging. What influences, protects your body over the years.

PMID- 16404321
TI  - Common painkillers may raise blood pressure in women.

PMID- 16404322
TI  - Study shows echinacea doesn't prevent or ease cold symptoms.

PMID- 16404323
TI  - Moderate exercise may reduce ovarian cancer risk.

PMID- 16404324
TI  - Insomnia no more. Helping yourself get a good night's sleep.

PMID- 16404325
TI  - Bird flu. Surviving a pandemic.

PMID- 16404327
TI  - Mismatched sexual desire. Navigating through the differences.

PMID- 16404326
TI  - Mayo Clinic office visit. Hospital dismissal planning. An interview with Dennis
      Manning, M.D., and Natasha Matt-Hensrud, B.S.N., M.P.H.

PMID- 16404328
TI  - How great is my risk of lung cancer as a nonsmoker?

PMID- 16404329
TI  - How often do I need to buy new walking or running shoes?

PMID- 16404330
TI  - Does CoQ10 reduce muscle pain caused by taking statins?

PMID- 16404331
TI  - Depression and heart disease. The connection between two common conditions.

PMID- 16404332
TI  - Digital mammography may have advantages for some women.

PMID- 16404333
TI  - Trans fat content added to nutrition facts labels.

PMID- 16404334
TI  - Know your knees. A guide to preventing and treating common problems.

PMID- 16404336
TI  - Age and surgery. Procedures can be safe in later years.

PMID- 16404337
TI  - Mayo Clinic office visit. Irritable bowel syndrome. An interview with Amy Foxx
      Orenstein, M.D.

PMID- 16404338
TI  - Sodium and you. Too much of a good thing?

PMID- 16404340
TI  - My doctor asked me to quit smoking before I have surgery in a few months. Is this
      really necessary?

PMID- 16404339
TI  - I'm taking a generic version of Synthroid and I don't seem to feel as well as
      when I took the brand-name version. Is there a difference between the two?

PMID- 16404341
TI  - Can energy drinks really boost my energy?

PMID- 16404342
TI  - Association of CYP2E1 gene polymorphism with predisposition to cancer
      development.
AB  - We summarize research results on association of cytochrome P450 2E1 (CYP2E1)
      genetic polymorphisms with the development of ecologically determined cancers.
      Cytochrome P450 monooxygenase enzyme system is involved in metabolic activation
      of procarcinogens, which is an important stage during normal cell transformation
      into a malignant one. Studies of association between CYP2E1 gene polymorphisms
      and the risk of cancer development are of particular interest, since the enzyme
      participates in bio-transformation of numerous procarcinogens. We place special
      emphasis on characterization of known CYP2E1 polymorphisms and analysis of their
      role in pathogenesis of various cancer types. Results obtained provide evidence
      on association of CYP2E1 genetic polymorphisms both with increased and decreased
      risk of development of malignant tumors. Ethnic and geographic peculiarities were
      also identified for frequencies of CYP2E1 variants distribution.

PMID- 16404343
TI  - The role of E-cadherin/catenin complex in laryngeal cancer.
AB  - In this review the role of the epithelial E-cadherin/catenin complex in cases of
      laryngeal cancer is discussed. Cancer of the larynx remains the second most
      common head and neck malignancy. The E-cadherin/catenin complex expression is
      abnormal in laryngeal squamous cell carcinomas. Loss or reduction of E-cadherin
      expression is especially observed in supraglottic larynx cancer in relation with
      poor histological differentiation and/or lymph nodes metastases. Controversial
      results in some studies regarding the role of the E-cadherin/catenin complex in
      various anatomical parts of the larynx have been reported. Further studies are
      needed to establish the importance of the E-cadherin/catenin complex as a
      potential biomarker in laryngeal cancer diagnosis and prognosis.

PMID- 16404344
TI  - Influence of aconitine-containing herbal extract BC1 on proliferative and
      electrokinetic characteristics of endothelial cells.
AB  - AIM: To evaluate the influence of new antitumor preparation BC1 produced on the
      base of Aconitum species on viability and electrokinetic properties of
      endothelial cells for estimation of mechanisms of its antitumor and
      antimetastatic activity. MATERIALS AND METHODS: Cytotoxic/cytostatic action of
      BC1 toward murine aorta endothelial cells (MAEC) and tumor LLC/R9 cells was
      studied using MTT-test. Apoptotic rate of MAEC was performed by flow cytometry.
      Electrokinetic properties of MAEC were determined by linear rate of their
      migration in electric field with the voltage of 20 V/cm. RESULTS: After 24 h of
      incubation with BC1, IC50 for actively proliferating was 0.95 -/+ 0.06 microg/ml
      and was 9-fold and 14-fold lower (p < 0.05) than that index for confluent
      endotheliocytes and LLC/R9 cells respectively. The ability of BC1 to alter
      electrokinetic characteristics of MAEC and to induce apoptosis has been
      demonstrated. At the concentration of IC50/10, 1 caused 2-fold decrease of zeta
      potential and surface density of charge of compared to the control (p < 0.05)
      whilst at the concentration of IC50/20 - inversion of surface charge of the
      majority (80%) of the cells in association with BC1-induced apoptosis.
      CONCLUSION: High sensitivity of actively proliferating MAEC to the action of BC1
      was revealed as well as the ability of that preparation to cause apoptosis and
      inversion of surface charge of endothelial cells.

PMID- 16404345
TI  - Latent membrane protein-1 of Epstein - Barr virus increases sensitivity to
      arsenic trioxide-induced apoptosis in nasopharyngeal carcinoma cell.
AB  - BACKGROUND AND AIM: Epstein - Barr virus (EBV)-encoded LMP1 is suggested to have
      an important role in the pathogenesis and development of nasopharyngeal carcinoma
      (NPC). Our previous study showed that As2O3 exhibited growth inhibition of NPC in
      animal model. Here, we further explore whether LMP1 is involved in As2O3
      anticancer effects in NPC cell line. METHODS: Both the stable expressing LMP1
      cell line HNE1-LMP1 and its parental cell line HNE1 without LMP1 expression were
      used as in vitro models to assess arsenic trioxide effect. Both cell lines were
      treated with As2O3 for 72 h. The median inhibition concentration (IC50) was
      assessed by the MTT assay. Apoptosis was observed by phase-contrast microscopy
      and TUNEL staining. The alteration of telomere lengths was detected by Southern
      blotting. RESULTS: IC50 for As2O3 in HNE1-LMP1 cells and HNE1 cells was 2.22 and
      5.09 micromol/L, respectively. After exposure to 2 and 4 micromol/L As2O3 for 72
      h, the apoptotic index in HNE1-LMP1 was 26.27 -/+ 1.3 and 49.13 -/+ 1.4%,
      respectively. On the contrary, in HNE1 cells the apoptotic index was 12.6 -/+ 0.9
      and 33.20 -/+ 1.3%, respectively. As compared with parental cell line HNE1, HNE1
      LMP1 cells were more sensitive to growth inhibition and apoptosis (p < 0.001).
      The elongation of telomere length was also found in HNE1-LMP1 cells. Meanwhile,
      longer telomeres in HNE1-LMP1 cells failed to maintain telomere stabilization,
      instead, it prone to be shortened when exposure to As2O3, as comparing with HNE1
      cells. CONCLUSION: LMP1 plays important role in enhancing NPC cell response to
      As2O3. The elongation of telomere length induced by LMP1 may contribute to the
      mechanisms of As2O3 sensitivity.

PMID- 16404346
TI  - Activation of antitumor cytotoxic T lymphocytes by fusion of patient-derived
      dendritic cells with autologous osteosarcoma.
AB  - BACKGROUND AND AIM: Fusion of human dendritic cells (DCs) with tumor cells is an
      effective approach for delivering tumor antigens to DCs, and DC/tumor fusion
      cells are potent stimulators of autologous T cells. However, the integration and
      morphology of DC/osteosarcoma fusion cells has not been examined. This study was
      designed to investigate the antitumor effects of tumor vaccine produced by
      electrofusion between human osteosarcoma cells and DCs. METHODS: In the present
      study, we eletrofused patient-derived DCs to autologous osteosarcoma cells. The
      fusion cells possessed the properties of both patient cells. After electrofusion,
      the cytoplasm of the two cells was integrated, whereas their nuclei remained
      separate entities. The intracellular structure was observed on fusion cells under
      the transmission electron microscope. RESULTS: Coculture of patient-derived
      peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in
      activation of T cells as assessed by standard cytotoxic T lymphocytes (CTLs)
      assays. CONCLUSIONS: The present study provides valid evidence on integration of
      human DCs and tumor cells and links their properties to T cell activation. The
      fusion cells may thus represent a promising strategy for DC-based immunotherapy
      of patients with osteosarcoma.

PMID- 16404347
TI  - Evaluation of fluorenhymustine as a rationally designed novel anticancer agent.
AB  - AIM: To develop a rationally designed new nitrogen mustard namely
      Fluorenhymustine (compound 2), where N,N'-bis(2chloro-ethyl)amino group, the
      established anticancer functionality, is attached to the 2-ethyl fluorenone
      hydantoin moiety. MATERIALS AND METHODS: Starting from fluorenone hydantoin, a 3
      step synthetic procedure was followed to obtain the title compound. 4-(4
      Nitrobenzyl)pyridine was used to assess its chemical alkylating activity. Murine
      tumors (Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180)) were used to
      assess its in vivo activity. Its cytotoxicity was determined in vitro in MCF-7
      human breast tumor cell line, toxicity - in vivo in normal and EAC bearing mice.
      3H-Thymidine and 3H-Uridine were employed to study its inhibitory effect on DNA
      and RNA synthesis respectively in S-180 tumor cells in vitro. RESULTS: Alkylating
      activity of fluorenmustine exceeded that of N-di(2-chloroethyl)amine used as a
      standard alkylating compound. It has displayed an excellent and reproducible
      antitumor activity in vivo against EAC and S-180 comparable to that of 5
      fluorouracil judging by the increase in median survival times of treated animals.
      It also significantly increased the life span of mice bearing advanced tumors for
      6 days before the drug challenge. However in vitro screening in MCF-7 did not
      reveal any significant cytotoxicity. The compound did not adversely affect
      hematopoiesis at its optimum dose. Drug-induced hepatotoxicity and nephrotoxicity
      were also not detected. It inhibited the synthesis of DNA and RNA in S-180 tumor
      cells at 8 microM concentration. CONCLUSION: Results indicated promising
      chemotherapeutic potential of Fluorenhymustine.

PMID- 16404348
TI  - Total proteolytic activity and levels of the main proteinase inhibitors in blood
      plasma of mice bearing Lewis lung carcinoma upon development of resistance to
      cisplatin.
AB  - The aim of the study was to evaluate the total proteolytic activity (TPA) and the
      content of alpha-1-proteinase inhibitor (alpha1PI) and alpha-2-macroblobulin
      (alpha2M) in the blood plasma of mice with Lewis lung carcinoma (LLC) upon the
      development of resistance to cisplatin. METHODS: Experimental LLC model with
      different sensitivity to cisplatin was obtained by sequential subcutaneous
      transplantation of LLC cells from cisplatin-treated animals. TPA, alpha1PI and
      alpha2M levels were evaluated by standard biochemical methods. RESULTS: It has
      been shown that the development of LLC resistance to cisplatin is accompanied by
      the increase of TPA activity and the level of the main proteinase inhibitor -
      alpha1PI. Despite the high level of alpha1PI in the resistant variant of LLC
      compared to parental tumor, the increase of TPA/alpha1PI ratio indicated the
      deficiency of that inhibitor in the blood of mice bearing cisplatin-resistant
      tumors, that promotes metastasis. The growth of both resistant to cisplatin LLC
      and sensitive variant was accompanied with the reduction of the alpha2M
      concentration. CONCLUSIONS: Upon the development of resistance to cisplatin in
      vivo the shift in the balance between proteinases and their inhibitors toward
      activation of TPA simultaneously with the increased metastasis is taking place.

PMID- 16404349
TI  - Response of different organs of immune system of mice upon administration
      bacterial CpG DNA.
AB  - CpG DNA are potent immunostimulator and currently being tested as adjuvant in
      immunotherapy of various diseases. THE AIM of this study was to investigate the
      effects of a single dose of bacterial CpG DNA challenge on response of murine
      immune system organs and on a zeta-potential of different lymphoid organ cells
      and peritoneal macrophages in normal and tumor-bearing mice. METHODS: Indexes and
      cellularity of immune organs of mice were evaluated. Z-potential was measured by
      cellular electrophoresis. RESULTS: Subcutaneous administration of CpG DNA induced
      local transitory hyperplasia of lymph nodes, moderate increase of splenic index
      and total spleen cellularity, whereas intraperitoneal injection of CpG DNA caused
      full-blown spleen enlargement and increase of splenocyte content, and also mice
      showed transitory aseptic peritonitis. Response of thymus on challenge of CpG DNA
      was bi-phase: initial phase - response on antigen as stimulus, and late
      proliferative phase. It was noted that tumor growth does not affect zeta
      potential in peritoneal macrophages and mononuclear lymphocytes, but causes
      increase of zeta-potential on thymocytes and decreases it in lymphocytes from
      lymph nodes. Furthermore, single administration of CpG DNA normalizes of
      thymocytes and lymph nodes lymphocytes zeta-potential and increases it in
      peritoneal macrophages and mononuclear lymphocytes. CONCLUSION: The findings
      demonstrate a close correlation between the hyperplasia of lymphoid follicles
      induced by challenge of CpG DNA and increase of their cellularity. Observed Z
      potential alterations of immune system cells after CpG DNA immunization evidence
      on more significant polyanion accumulation on the surface of splenic macrophages
      and mononuclear cells.

PMID- 16404350
TI  - Diurnal rhythmicity of thiobarbituric acid reactive substances and antioxidants
      in experimental mammary carcinogenesis.
AB  - AIM: Circadian rhythms of reactive oxygen species and antioxidants have been the
      subject of considerable interest in recent years due to their crucial role in the
      development of malignant tumors. Our aim was to analyze the circadian pattern of
      lipid peroxidation by-products (TBARS) and antioxidants status in 7,12
      dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinogenesis. METHODS:
      Mammary tumors were developed in Wistar rats, blood samples were collected at a
      regular interval of 4 h throughout the 24 h period and TBARS content and
      antioxidant enzymes activities (superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx)) were estimated by colorimetric methods. The
      Cosinorwin computer software program was used to analyze the characteristics of
      biochemical rhythms. RESULTS: In mammary carcinogenesis, the acrophase of
      thiobarbituric acid reactive substances and antioxidant enzymes (SOD, CAT, GPx)
      in blood were found to be delayed, whilst mesor values for TBARS level -
      increased, and values for SOD, CAT, GPx activities - decreased. Significant r
      values indicate the disruption of lipid peroxidation-antioxidants rhythms in
      mammary carcinogenesis. CONCLUSION: The present investigation suggests that the
      circadian pattern of blood lipid peroxidation and antioxidants in rats with
      mammary carcinoma are markedly desynchronized as compared to normal rats.

PMID- 16404351
TI  - The sensitivity of chemioresistant human tumor explants to lysis by activated and
      nonactivated autological lymphocytes: a pilot study.
AB  - AIM: The comparative study of antitumor action of peripheral blood lymphocytes
      (PBL) and lymphokin-activated killer cells (LAK) on autologous cell of
      chemoresistant and chemosensitive human soft tissue sarcomas and tumors of
      epithelial origin. MATERIALS AND METHODS: Tumor explants (15 samples of soft
      tissue sarcomas, 10 samples of cervical and ovarian carcinomas) were cultivated
      with autologous lymphocytes in double diffusion chambers. Evaluation of the
      results was done on the basis of morphological criteria of explants growth.
      RESULTS: The results have shown that in the patients with the resistant soft
      tissue sarcomas and carcinomas LAK possess more pronounced antitumor action, than
      non-activated lymphocytes, whilst PBL possess higher antitumor action on
      sensitive epithelial tumors than that on soft tissue sarcoma. CONCLUSION: LAK
      possess antitumor action toward chemoresistant tumors of different origin and
      localization.

PMID- 16404352
TI  - Involvement of human beta-defensin-2 in proliferation of transformed cells of
      human cervix.
AB  - AIM: To evaluate the influence of human beta-defensin-2 (hBD-2) on viability and
      proliferation of cultured human epithelial cells and the patterns of hBD-2
      expression in normal tissues and early-stage human cervical neoplasia in the
      relation to proliferative state of these cells. MATERIALS AND METHODS: The
      influence of recombinant hBD-2 on viability and proliferation of cultured cells
      of A431 and M-HeLa lines in vitro was performed by MTT-test, 3H-thymidine
      incorporation and cell counting techniques. Immunohistochemical analysis of
      expression of hBD-2 and PCNA in tissue samples (10 normal cases (control), 30
      carcinomas of the cervix uteri: 15 - squamous cell carcinoma in situ (Stage 0),
      and 15 squamous cell carcinoma (Stage Ia)) was performed with the use of anti-hBD
      2 and anti-PCNA-mAbs, respectively. RESULTS: We have revealed that hBD-2
      significantly stimulated proliferation of A431 and M-HeLa cells in a
      concentration-dependent manner in the range of 0.1-2 microg/ml, whilst at higher
      concentrations (> 3-5 microg/ml) it negatively influenced cell viability. The
      results of immunohistochemical study have shown that malignant transformation of
      human cervical epithelium is accompanied by the increase of expression of hBD-2
      and PCNA. However, the correlative analysis of the expression of the mentioned
      markers has revealed no relation between them. CONCLUSION: The effect of hBD-2 on
      viability and proliferation of cultured epithelial cells possesses a
      concentration-dependent character. Expression of hBD-2 is increased in early
      stage cervical carcinoma.

PMID- 16404353
TI  - Patterns of expression of TSC-22 protein in astrocytic gliomas.
AB  - AIM: To evaluate expression patterns of protein product of putative tumor
      suppressor gene TSC-22 in human astrocytic tumors by immunohistochemical
      approach. METHODS: Plasmid pET-23d-TSC22 was constructed for the expression of
      human TSC-22 protein in bacterial system, and polyclonal rabbit antibodies
      against recombinant TSC-22 were produced. Immunohistochemical analysis of TSC-22
      and GFAP expression with the use of anti-human-TSC-22- and anti-human-GFAP
      antibodies was performed on histological slides of astrocytic tumors. RESULTS:
      Immunohistochemical analysis has shown that the number of cells expressing TSC-22
      was significantly lower in glioblastoma tissues than that in diffuse astrocytoma.
      Double immunohistochemical staining of astrocytic tumors using anti-human-TSC-2-
      and anti-human-GFAP-antibodies showed that both TSC-22 and GFAP expression is co
      localized in astrocytes. CONCLUSION: TSC-22 protein is expressed in astrocytes,
      but not in macrophage/microglial cells. In more aggressive forms of astrocytic
      tumors decreased expression of TSC-22 mRNA correlates with its lowered expression
      on protein level.

PMID- 16404354
TI  - Rearrangements of IgH, TCRD and TCRG genes as clonality marker of childhood acute
      lymphoblastic leukemia.
AB  - AIM: Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are
      excellent patient-specific targets for clonality studies and monitoring of acute
      lymphoblastic leukemia (ALL). THE AIMS of the study were to select the optimum
      panel of primers, evaluate incidence of particular types of monoclonal and
      oligoclonal gene rearrangements and observe alteration of rearrangement profile
      between diagnosis of ALL and subsequent relapse(s). METHODS: We used polymerase
      chain reaction (PCR) for amplification of junctional region of rearranged IgH,
      TCRD and TCRG genes in combination with heteroduplex analysis in polyacrylamide
      gel. RESULTS: TCRD gene rearrangements were detected in 64%, TCRG - in 45%, and
      IgH - in 79% of B-precursor ALL patients. For patients with T-ALL, TCRD gene
      rearrangements were found in 47%, TCRG gene - in 66%, and IgH - in 19% of cases.
      Evaluation of biallelic and oligoclonal rearrangements was performed in the
      study. The highest incidence of oligoclonal rearrangements - 25% was shown for
      IgH gene in patients with B-precursor ALL. Seven pair cases of patients with de
      novo leukemia and relapses were analyzed and revealed subclonal deviation in
      rearrangements of IgH or TCR genes during disease evolution. CONCLUSION: We
      propose a panel of 13 types of rearrangements (primer pairs) sufficient for tumor
      cell clonality detection in 96% of patients with ALL. Applications of PCR-based
      analysis of rearranged IgH, TCRD and TCRG genes for discrimination of mono- and
      oligoclonality and identification of the origin of relapse were demonstrated.

PMID- 16404355
TI  - Significance of VH genes mutation status for prognosis of CLL patients.
AB  - AIM: The aim of this study was to evaluate significance of VH mutation status for
      prognosis of B-cell chronic lymphocytic leukemia (B-CLL) patients in comparison
      with other prognostic markers. MATERIALS AND METHODS: The VH mutation status was
      evaluated in 43 B-CLL patients by RT-PCR amplification and nucleotide sequencing,
      and CD38 expression - by two-color FACS analysis. The prognostic influence of VH
      mutation rate and CD38 expression level was tested by different statistical
      methods. RESULTS: The increasing number of advanced cases over the follow-up
      period, shorter median time from diagnosis to start of second line therapy, worse
      response to fludarabine treatment, poor survival for early stages B-CLL were
      found in unmutated versus mutated CLL patients. The significance of CD38
      expression for CLL prognosis was revealed as predictor for response for
      fludarabine treatment and time of progression in advanced stages. The correlation
      between CD38 expression and VH mutation status was not found. CONCLUSION:
      Simultaneous determination of VH mutation status and CD38 expression may be
      helpful for prediction of CLL prognosis.

PMID- 16404356
TI  - Effect of landomycin E on expression of mRNA coding for transforming growth
      factor beta ligands and specific receptors in MCF-7 cells.
AB  - The aim of the present study was to investigate regulation of mRNA, coding for
      TGFbeta ligands and specific receptors, by novel antitumor antibiotic landomycin
      E (LE) in human breast adenocarcinoma cells of MCF-7 line, sensitive and
      resistant to anti-cancer agent doxorubicin. METHODS: Semi-quantitative analysis
      of mRNA expression was estimated using RT-PCR and DNA gel-electrophoresis
      methods. For comparison, another anti-cancer drug doxorubicin (adriamycin) was
      utilized. THE RESULTS obtained indicate that LE induces up-regulation of mRNA
      coding for TGFbeta receptors type I and type II in MCF-7 cells, as well as in
      their doxorubicin-resistant sub-line. CONCLUSION: Anti-tumor action of LE may be
      mediated by TGFbeta, and a signaling pathway of this cytokine is not affected by
      the development of tumor cell resistance to doxorubicin.

PMID- 16404357
TI  - Effect of photodynamic therapy on tumor angiogenesis and metastasis in mice
      bearing Lewis lung carcinoma.
AB  - AIM: To investigate the influence of photodynamic therapy (PDT) on the tumor
      angiogenesis and metastasis. METHODS: The effect of PDT with a photosensitizer 5
      aminolaevulinic acid (ALA) on tumor metastasis and angiogenesis was studied on
      the model of subcutaneously implanted Lewis lung carcinoma (3LL) in C57Bl/6 mice.
      VEGF level in blood serum of animals was evaluated by ELISA. RESULTS: It has been
      shown that application of ALA-PDT resulted in the lowered rate of metastatic
      spreading and decreased VEGF level in blood serum of 3LL-bearing mice, and
      morphologic alterations of vascular system in tumor tissue. CONCLUSION: The
      antitumor action of PDT using ALA as a photosensitizer is caused partly by
      antimetastatic and photodamaging effect mediated by vascularization disturbances
      in tumor tissue.

PMID- 16404358
TI  - Elevation of the efficacy of antitumor vaccine prepared on the base of lectines
      from B. subtilis B-7025 upon its combined application with probiotics in vivo.
AB  - The aim of the work was to evaluate in vivo the possible enhancement of efficacy
      of antitumor vaccine prepared on the base of cytotoxic lectine from B. subtilis B
      7025 by its combination with probiotic mixture of Enterococcus faecium K-50 and
      Saccharomyces cerevisiae 14K or their metabolic products. MATERIALS AND METHODS:
      Experiments were carried out on the models of solid sarcoma 37 (S37) and
      metastatic Lewis lung carcinoma (3LL). Efficacy of treatment was evaluated by
      parameters of tumor growth, median survival time of experimental animals and
      volume of metastases. RESULTS: We have shown that combined application of
      antitumor vaccine with pro-and/or prebiotic resulted in synergistic effect in the
      therapy S37-bearing mice, whilst in 3LL-bearing animals application of vaccine
      along with prebiotic inhibited metastasis by 2-2.5-fold compared to animals
      treated by vaccine only. CONCLUSION: Application of pre- and probiotics (E.
      faecium K-50 and S. cerevisiae) markedly elevates efficacy of antitumor vaccine
      in vivo.

PMID- 16404359
TI  - Residual lung lesions after completion of chemotherapy for gestational
      trophoblastic neoplasia: should we operate?
AB  - The significance of residual lung metastasis from malignant gestational
      trophoblastic neoplasm (GTN) after the completion of chemotherapy is unknown. We
      currently do not advocate resection of these masses. Here, we investigate the
      outcome of these patients. Patients with residual lung abnormalities after the
      completion of treatment for GTN were compared to those who had a complete
      radiological resolution of the disease. None of the residual masses post
      treatment were surgically removed. In all, 76 patients were identified. Overall
      53 (70%) patients had no radiological abnormality on CXR or CT after completion
      of treatment. Eight (11%) patients had residual disease on CXR alone 15 patients
      had residual disease on CT (19%). During follow-up, two patients (2.6%) relapsed.
      One of these had had a complete radiological response post-treatment whereas the
      other had residual disease on CT. Patients with residual lung lesions after
      completing treatment for GTN do not appear to have an increased chance of relapse
      compared to those with no residual abnormality. We continue to recommend that
      these patients do not require pulmonary surgery for these lesions.

PMID- 16404360
TI  - SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel
      irinotecan as first-line therapy for ovarian cancer.
AB  - The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy
      as first-line treatment for advanced epithelial ovarian carcinoma was assessed.
      One hundred patients were randomised to receive four 3-weekly cycles of
      carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of
      docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200
      mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an
      eight-cycle treatment completion rate that was statistically greater than 60%
      (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55
      78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents.
      In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to
      treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in
      arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%).
      Of patients with radiologically evaluable disease at baseline, 50 and 48%
      responded to therapy in arms A and B, respectively; at median 17.1 months' follow
      up, median progression-free survival was 17.1 and 15.9 months, respectively.
      Although both arms just failed to meet the formal statistical feasibility
      criteria, the observed completion rates of around 70% were reasonable. The
      addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was
      generally well tolerated although associated with increased gastrointestinal
      toxicity. Further exploratory studies of topoisomerase-I inhibitors in this
      setting may be warranted.

PMID- 16404361
TI  - SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first
      line chemotherapy for ovarian cancer.
AB  - The feasibility of sequential carboplatin followed by docetaxel-based therapy for
      untreated ovarian cancer was determined. Patients received four q3w cycles of
      carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1)
      (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8)
      (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly
      (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment
      arm. None of the arms demonstrated an eight cycle completion rate
      (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater
      than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria,
      although only the completion rate in arm C was clearly worse than this level. The
      overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients.
      In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21
      out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up
      (median 30 months), median progression-free survival times were: arm A 15.5
      months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7
      months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4
      haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea
      was markedly increased in both gemcitabine-containing arms (P=0.001) but was
      worse in arm C. Although just failing to rule out eight cycle completion rates
      less than 60%, within the statistical limitations of these small cohorts, the
      overall results for arms A and B are encouraging. Larger phase III studies are
      required to test these combinations.

PMID- 16404362
TI  - 'A phase II study of oral uracil/ftorafur (UFT) plus leucovorin combined with
      oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic
      colorectal cancer'.
AB  - This phase II trial was performed to evaluate the efficacy and tolerability of a
      new combination of Uracil/Ftorafur (UFT)/leucovorin (LV) and oxaliplatin in
      patients (pts) with metastatic colorectal cancer (MCRC) who had not received
      prior chemotherapy for metastatic disease. Between February 2002 and October
      2002, 64 patients received UFT 300 mg m(-2) day(-1) and LV 90 mg day(-1) from day
      1 to day 14 combined with oxaliplatin 130 mg m(-2) on day 1, every 3 weeks. All
      patients were evaluable for safety analysis and 58 of 64 patients were eligible
      for efficacy. Responses were reviewed by an independent review committee. Of the
      58 per-protocol defined assessable patients, 1 complete response and 20 partial
      responses were observed yielding a response rate of 34% (95% CI: 22-47). The
      median response duration was 8.74 months (range 1.6-14). The median time to
      progression and the median survival were 5.88 months (95% CI: 4.34-8.21) and 18.2
      months (95% CI: 10-20.7), respectively. Diarrhoea and peripheral neuropathy were
      the most frequent and predictable toxicities. These events were reversible,
      noncumulative and manageable. Grade 3 diarrhoea occurred in only 11% of the
      patients. No grade 4 gastrointestinal toxicity was reported in the study. The
      incidence of grade 3/4 (National Cancer Institute Common Toxicity Criteria 2: NCI
      CTC 2) peripheral neuropathy was 15%. Haematological toxicity was of mild to
      moderate intensity with 10% of the patients with Grade 3/4 neutropenia without
      any episode of complication. The TEGAFOX regimen, a new combination using UFT/LV
      and oxaliplatin every 3 weeks is feasible on an outpatient basis. The combination
      is safe and active and may offer a promising alternative to the intravenous
      route. Nevertheless this efficacy results should be confirmed by randomized phase
      III trials.

PMID- 16404363
TI  - Macrophages promote angiogenesis in human breast tumour spheroids in vivo.
AB  - An in vivo model has been established to study the role of macrophages in the
      initiation of angiogenesis by human breast tumour spheroids in vivo. The extent
      of the angiogenic response induced by T47D spheroids implanted into the dorsal
      skinfold chamber in nude mice was measured in vivo and compared to that induced
      by spheroids infiltrated with human macrophages prior to implantation. Our
      results indicate that the presence of macrophages in spheroids resulted in at
      least a three-fold upregulation in the release of vascular endothelial growth
      factor (VEGF) in vitro when compared with spheroids composed only of tumour
      cells. The angiogenic response measured around the spheroids, 3 days after in
      vivo implantation, was significantly greater in the spheroids infiltrated with
      macrophages. The number of vessels increased (macrophages vs no macrophages 34+/
      1.9 vs 26+/-2.5, P<0.01), were shorter in length (macrophages vs no macrophages
      116+/-4.92 vs 136+/-6.52, P<0.008) with an increased number of junctions
      (macrophages vs no macrophages 14+/-0.93 vs 11+/-1.25, P<0.025) all parameters
      indicative of new vessel formation. This is the first study to demonstrate a role
      for macrophages in the initiation of tumour angiogenesis in vivo.

PMID- 16404364
TI  - Expression of cytoplasmic and nuclear Survivin in primary and secondary human
      glioblastoma.
AB  - Clinically, human glioblastoma (GBM) may develop de novo or from a low-grade
      glioma (secondary GBM), and molecular alterations in the two pathways may differ.
      This study examined the status of Survivin expression and apoptosis in 30 primary
      and 26 secondary GBMs. Our results show that cytoplasmic Survivin positivity was
      significantly (P<0.001) more frequent in primary GBMs (83%) than that in
      secondary GBMs (46%). In addition, an inverse correlation of cytoplasmc Survivin
      positivity with GBM apoptotic index, and a positive association between
      cytoplasmic Survivin and size of the tumours were observed. These results suggest
      that cytoplasmic Survivin, via its antiapoptotic function, may be involved in the
      tumorigenesis of many primary GBMs, but only in a small fraction of secondary
      GBMs. Furthermore, the overall progression times from low-grade precursor lesions
      to secondary GBMs were significantly shorter (P<0.05) in cytoplasmic Survivin
      positive cases (mean, 15.6 months) than those in Survivin-negative cases (mean,
      23.8 moths), and the positive expression level of Survivin in cytoplasm was
      upregulated in most secondary GBMs when compared to matched pre-existing low
      graded lesions. These results suggest that the increased accumulation of Survivin
      in the cytoplasm of more malignant glioma cells may prove to be a selective
      advantage, thus accelerating progression to a more aggressive phenotype.

PMID- 16404365
TI  - The effect of surgically induced ischaemia on gene expression in a colorectal
      cancer xenograft model.
AB  - Delays in tissue fixation following tumour vascular clamping and extirpation may
      adversely affect subsequent protein and mRNA analysis. This study investigated
      the effect of surgically induced ischaemia in a xenograft model of a colorectal
      cancer on the expression of a range of prognostic, predictive, and hypoxic
      markers, with a particular emphasis on thymidylate synthase. Vascular occlusion
      of human tumour xenografts by D-shaped metal clamps permitted defined periods of
      tumour ischaemia. Alterations in protein expression were measured by
      immunohistochemistry and spectral imaging, and changes in mRNA were measured by
      reverse transcriptase-polymerase chain reaction. Thymidylate synthase expression
      decreased following vascular occlusion, and this correlated with cyclin A
      expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen.
      There were significant changes in the expression of several hypoxic markers, with
      carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels
      were also noted to change following tumour clamping. In this xenograft model,
      surgically induced tumour ischaemia considerably altered the gene expression
      profiles of several prognostic and hypoxic markers, suggesting that the degree of
      tumour ischaemia should be minimised prior to tissue fixation.

PMID- 16404366
TI  - Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon,
      stomach, prostate and lung cancers.
AB  - Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many
      immunotherapeutic approaches, but little data are available about Ep-CAM
      expression in major human malignancies with respect to level, frequency, tumour
      stage, grade, histologic tumour type and impact on survival. We analysed by
      immunohistochemical staining tissue microarrays with 4046 primary human carcinoma
      samples from colon, stomach, prostate and lung cancers for both frequency and
      intensity of Ep-CAM expression under highly standardised conditions. A total of
      3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7%
      (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers
      (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was
      found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and
      13.5% of lung cancers. The only significant correlation of Ep-CAM expression with
      tumour grading was observed in colon cancer where high-level Ep-CAM expression on
      grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous
      carcinomas of the lung had a lower percentage of high-level Ep-CAM expression
      compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and
      17.3% of tumours being Ep-CAM negative. With the exception of moderately
      differentiated colon carcinoma, where patients not expressing Ep-CAM on their
      tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression
      with survival did not reach statistical significance for any of the other cancer
      indications and subgroups. In conclusion, the data strongly support the notion
      that Ep-CAM is a prime target for immunotherapies in major human malignancies.
      This is because the most common human cancers show (i) a low frequency of Ep-CAM
      negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given
      tumour, and (iii) for most cancers, an insignificant influence of tumour staging,
      grading and histology on Ep-CAM expression.

PMID- 16404367
TI  - Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas.
AB  - Oesophageal and gastric adenocarcinoma share an unexplained male predominance,
      which would be explained by the hypothesis that oestrogens are protective in this
      respect. We carried out a nested case-control study of hormone replacement
      therapy (HRT) among 299 women with oesophageal cancer, 313 with gastric cancer,
      and 3191 randomly selected control women, frequency matched by age and calendar
      year in the General Practitioners Research Database in the United Kingdom. Data
      were adjusted for age, calendar year, tobacco smoking, alcohol consumption, body
      mass index, hysterectomy, and upper gastrointestinal disorders. Among 1 619 563
      person-years of follow-up, more than 50% reduced risk of gastric adenocarcinoma
      was found among users of HRT compared to nonusers (odds ratio (OR), 0.48, 95%
      confidence interval (CI) 0.29-0.79). This inverse association appeared to be
      stronger for gastric noncardia (OR 0.34, 95% CI 0.14-0.78) and weaker for gastric
      cardia tumours (OR 0.68, 95% CI 0.23-2.01). There was no association between HRT
      and oesophageal adenocarcinoma (OR 1.17, 95% CI 0.41-3.32).

PMID- 16404368
TI  - Social inequalities in breast cancer mortality among French women: disappearing
      educational disparities from 1968 to 1996.
AB  - We investigated the time trends in social inequalities in breast cancer mortality
      with an analysis by age at death and birth cohort using a representative 1%
      sample of the French population and four subcohorts (1968-1974, 1975-1981, 1982
      1988 and 1990-1996). Causes of death were obtained by direct linkage with the
      French national death registry. Education was measured at the beginning of each
      period, and educational disparities in breast cancer mortality were studied among
      women aged 35-74 at the beginning of each period. In the 1970s, higher breast
      cancer mortality was found among higher educated women. This positive association
      progressively weakened and no association remained in the 1990s although it
      disappeared earlier among younger women. In an analysis by birth cohort, the same
      pattern was found among women born before 1925, whereas no association between
      education and mortality was observed among women born after 1925. Educational
      disparities in breast cancer mortality are currently changing and the previously
      observed positive gradient has disappeared. An important question is whether
      these relations are indirect, and due to changes in the prevalence of risk
      factors associated with education, but which we could not study.

PMID- 16404369
TI  - Adiponectin in relation to childhood myeloblastic leukaemia.
AB  - Adiponectin, an adipocyte-specific secretory protein known to induce apoptosis,
      has been reported to be inversely related to breast and endometrial cancers and
      recently found to inhibit proliferation of myeloid but not lymphoid cell lines.
      We hypothesised that adiponectin may be inversely associated with acute
      myeloblastic leukaemia (AML), but not with acute lymphoblastic leukaemia of B
      (ALL-B) or T (ALL-T) cell origin in children. Blood samples and clinical
      information were collected over the period 1996-2000 from 201 children (0-14
      years old) with leukaemia (22 AML, 161 ALL-B and 18 ALL-T cases) through a
      national network of childhood Hematology-Oncology units in Greece and from 201
      controls hospitalised for minor pediatric ailments. Serum adiponectin levels were
      measured under code, at the Beth Israel Deaconess Medical Center, Boston, MA, USA
      using a radioimmunoassay procedure. Each of the three leukaemia groups was
      compared with the control group through multiple logistic regression. Odds ratios
      (OR) and 95% confidence intervals (95% CI) for an increase of adiponectin equal
      to 1 s.d. among controls were estimated controlling for gender, age, as well as
      for height and weight, expressed in age-gender-specific centiles of Greek growth
      curves. Adiponectin was inversely associated with AML (OR=0.56; 95% CI, 0.34
      0.94), whereas it was not significantly associated with either ALL-B (OR=0.88;
      95% CI, 0.71-1.10) or ALL-T (OR=1.08; 95% CI, 0.67-1.72). Biological plausibility
      and empirical evidence point to the importance of this hormone in the
      pathogenesis of childhood AML.

PMID- 16404370
TI  - Magnetic field exposure and long-term survival among children with leukaemia.
AB  - We examined the association between magnetic field (MF) exposure and survival
      among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric
      Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible
      children under treatment, 482 (29%) participated and personal 24-h MF
      measurements were obtained from 412 participants. A total of 386 children with
      ALL and 361 with B-precursor ALL were included in the analysis of event-free
      survival (time from diagnosis to first treatment failure, relapse, secondary
      malignancy, or death) and overall survival. After adjustment for risk group and
      socioeconomic status, the event-free survival hazard ratio (HR) for children with
      measurements >/=0.3 muT was 1.9 (95% confidence interval (CI) 0.8, 4.9), compared
      to <0.1 muT. For survival, elevated HRs were found for children exposed to >/=0.3
      muT (multivariate HR=4.5, 95% CI 1.5-13.8) but based on only four deaths among 19
      children. While risk was increased among children with exposures above 0.3 muT,
      the small numbers limited inferences for this finding.

PMID- 16404373
TI  - Getting beyond Hwang.

PMID- 16404371
TI  - Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for
      adenocarcinoma of the cervix compared to women with normal cytology in The
      Netherlands.
AB  - We present the type-distribution of high-risk human papillomavirus (HPV) types in
      women with normal cytology (n=1467), adenocarcinoma in situ (ACIS) (n=61),
      adenocarcinoma (n=70), and squamous cell carcinoma (SCC) (n=83). Cervical
      adenocarcinoma and ACIS were significantly more frequently associated with HPV18
      (OR(MH) 15.0; 95% CI 8.6-26.1 and 21.8; 95% CI 11.9-39.8, respectively) than
      normal cytology. Human papillomavirus16 was only associated with adenocarcinoma
      and ACIS after exclusion of HPV18-positive cases (OR(MH) 6.6; 95% CI 2.8-16.0 and
      9.4; 95% CI 2.8-31.2, respectively). For SCC, HPV16 prevalence was elevated
      (OR(MH) 7.0; 95% CI 3.9-12.4) compared to cases with normal cytology, and HPV18
      prevalence was only increased after exclusion of HPV16-positive cases (OR(MH)
      4.3; 95% CI 1.6-11.6). These results suggest that HPV18 is mainly a risk factor
      for the development of adenocarcinoma whereas HPV16 is associated with both SCC
      and adenocarcinoma.

PMID- 16404374
TI  - Genetically modified mush.

PMID- 16404375
TI  - Biotech jostles with pharma for slice of HIV market.

PMID- 16404376
TI  - Serono changes tack.

PMID- 16404377
TI  - Shift toward early-stage deals favors biotechs.

PMID- 16404378
TI  - Lack of private financing hobbles emerging biotech regions.

PMID- 16404380
TI  - Tech transfer revs up.

PMID- 16404381
TI  - Wrestling with SUMO and bio-ontologies.

PMID- 16404383
TI  - Wrestling with SUMO and bio-ontologies.

PMID- 16404382
TI  - Wrestling with SUMO and bio-ontologies.

PMID- 16404384
TI  - European GMO labeling thresholds impractical and unscientific.

PMID- 16404386
TI  - ATCC not involved in negotiations with India.

PMID- 16404387
TI  - Activism unleashed...and unconscionable.

PMID- 16404388
TI  - Paying over the odds.

PMID- 16404391
TI  - Determining the meaning of claim terms.

PMID- 16404390
TI  - The licensing of DNA patents by US academic institutions: an empirical survey.

PMID- 16404392
TI  - Recent patent applications in microRNAs.

PMID- 16404393
TI  - Fishing for cancer models.

PMID- 16404394
TI  - Steroid regulation improves crop yield.

PMID- 16404395
TI  - RNAi tackles a sexually transmitted disease.

PMID- 16404397
TI  - Inference in Bayesian networks.

PMID- 16404399
TI  - Transgenic crops expressing Bacillus thuringiensis toxins and biological control.
AB  - The area devoted to growing transgenic plants expressing insecticidal Cry
      proteins derived from Bacillus thuringiensis (Bt) is increasing worldwide. A
      major concern with the adoption of Bt crops is their potential impact on
      nontarget organisms including biological control organisms. Regulatory frameworks
      should advocate a step-wise (tiered) approach to assess possible nontarget
      effects of Bt crops. Laboratory and glasshouse studies have revealed effects on
      natural enemies only when Bt-susceptible, sublethally damaged herbivores were
      used as prey or host, with no indication of direct toxic effects. Field studies
      have confirmed that the abundance and activity of parasitoids and predators are
      similar in Bt and non-Bt crops. In contrast, applications of conventional
      insecticides have usually resulted in negative impacts on biological control
      organisms. Because Bt-transgenic varieties can lead to substantial reductions in
      insecticide use in some crops, they can contribute to integrated pest management
      systems with a strong biological control component.

PMID- 16404398
TI  - Creation and implications of a phenome-genome network.
AB  - Although gene and protein measurements are increasing in quantity and
      comprehensiveness, they do not characterize a sample's entire phenotype in an
      environmental or experimental context. Here we comprehensively consider
      associations between components of phenotype, genotype and environment to
      identify genes that may govern phenotype and responses to the environment.
      Context from the annotations of gene expression data sets in the Gene Expression
      Omnibus is represented using the Unified Medical Language System, a compendium of
      biomedical vocabularies with nearly 1-million concepts. After showing how data
      sets can be clustered by annotative concepts, we find a network of relations
      between phenotypic, disease, environmental and experimental contexts as well as
      genes with differential expression associated with these concepts. We identify
      novel genes related to concepts such as aging. Comprehensively identifying genes
      related to phenotype and environment is a step toward the Human Phenome Project.

PMID- 16404400
TI  - Thinking outside the cell.

PMID- 16404402
TI  - Abdominal obesity, systolic blood pressure, and microalbuminuria in normotensive
      and euglycemic Korean men.
AB  - OBJECTIVES: To evaluate the relationship between abdominal obesity and
      microalbuminuria (MA) in normotensive, euglycemic Korean men. DESIGN: A cross
      sectional study at a health screening center. SUBJECTS: A total of 1321 healthy,
      normotensive Korean men, aged 20-78 years, with a fasting plasma glucose level
      <100 mg/dl. MEASUREMENTS: Height, weight, and waist; systolic blood pressure
      (SBP); diastolic blood pressures (DBP); urinary albumin to creatinine ratio
      (ACR); fasting glucose, insulin, lipids, C-reactive protein (CRP), and white
      blood cell count. Waist circumference (WC) was used to indicate abdominal obesity
      and a single measurement of ACR was used to estimate MA. We also calculated body
      mass index (BMI) based on weight and height. RESULTS: Mean BMI, WC, and SBP were
      significantly higher in subjects with MA than in those without (24.8+/-4.1 vs
      23.8+/-2.7 kg/m2, 86+/-9 vs 83+/-8 cm, and 115+/-5 vs 112+/-7 mmHg,
      respectively). Multiple logistic regression analyses showed that only WC and SBP
      were independent predictors of MA. CONCLUSION: WC and SBP were positively
      associated with MA in normotensive and euglycemic Korean men.

PMID- 16404403
TI  - Exposure to undernutrition in fetal life determines fat distribution, locomotor
      activity and food intake in ageing rats.
AB  - OBJECTIVE: To assess the long-term impact of undernutrition during specific
      periods of fetal life, upon central adiposity, control of feeding behaviour and
      locomotor activity. DESIGN: Pregnant rats were fed a control or low-protein (LP)
      diet, targeted to early (LPE), mid (LPM) or late (LPL) pregnancy or throughout
      gestation (LPA). The offspring were studied at 9 and 18 months of age.
      MEASUREMENTS: Adiposity was assessed by measuring weight of abdominal fat depots
      relative to body weight. Locomotor activity was assessed using an infrared sensor
      array system in both light and dark conditions. Hypothalamic expression of mRNA
      for galanin and the galanin 2 receptor (Gal2R) was determined using real-time
      PCR. RESULTS: At 9 months, male rats exposed to LP in utero had less fat in the
      gonadal depot, but were of similar body weight to controls. By 18 months, the
      males of groups LPA and LPM had more abdominal and less subcutaneous fat. Females
      deposited more fat centrally than males between 9 and 18 months of age, and this
      was more marked in groups LPA and LPL. Food intake was greater in LPM males.
      Among females hypophagia was noted in groups LPA and LPL. Expression of galanin
      and Gal2R were unaffected by maternal diet. Total locomotor activity was reduced
      in LPE males and all LP females in the light but not in the dark. CONCLUSION:
      Locomotor activity and feeding behaviour in aged rats are subject to prenatal
      programming influences. Fetal undernutrition does not programme obesity in rats
      without postnatal dietary challenge.

PMID- 16404404
TI  - A population-based study investigating the association between metabolic syndrome
      and hepatitis B/C infection (Keelung Community-based Integrated Screening study
      No. 10).
AB  - OBJECTIVES: We aimed to assess the association between metabolic syndrome (MS)
      and hepatitis B/C virus infection using a large population-based study. DESIGN
      AND METHODS: A population-based cross-sectional study design was adopted with a
      total of 53,528 subjects being enrolled from the integrated multiple diseases
      screening program in Keelung, Taiwan. Evidence of past hepatitis B/C infection,
      acquired during childhood or as a young adult, was identified during the two
      stage liver cancer screening part of the process. Information on biochemical
      markers and anthropometric measures related to MS, such as fasting blood sugar,
      triglyceride and high-density lipoprotein (HDL), abdominal circumference and
      blood pressure (BP), were collected routinely while screening for hypertension,
      type 2 diabetes, and hyperlipidemia. Logistic regression was used to estimate
      odds ratios and related 95% confidence intervals for the associations between MS
      and hepatitis B/C infection. RESULTS: High blood pressure (SBP > or = 135 mmHg or
      DBP > or = 85 mmHg) (adjusted odd ratio: 0.89 (0.83-0.94)) and high triglyceride
      (> or = 150 mg/dl) (adjusted odds ratio: 0.65 (0.60-0.69)) were, after adjusting
      for gender and age, inversely associated with being HBsAg positive (P<0.05). The
      likelihood of developing MS was lower in the HBsAg positive than the HBsAg
      negative (adjusted odds ratio: 0.84 (0.76-0.93)). A positive association between
      being anti-HCV positive and having low serum HDL (male <40 mg/dl, female <50
      mg/dl) was also noted (adjusted odds ratio: 1.61 (1.37-1.88) after controlling
      for gender and age). High triglyceride was inversely associated with being anti
      HCV positive (adjusted odds ratio: 0.63 (0.55-0.71). CONCLUSIONS: There is an
      inverse association between MS and hepatitis B virus infection whereas the
      association was heterogeneous for HCV infection with a positive association with
      abnormal serum HDL but an inverse association with hypertriglyceridemia.

PMID- 16404405
TI  - Resistance to body fat gain in 'double-muscled' mice fed a high-fat diet.
AB  - OBJECTIVE: To determine if myostatin deficiency attenuates body fat gain with
      increased dietary fat intake. METHODS: Normal and myostatin-deficient mice were
      fed control (8-10 kcal %fat) and high-fat (HF) (45 kcal %fat) diets for a period
      of 8 weeks, starting at 2 months of age. Body composition, including percent body
      fat, lean mass, and fat mass, were measured using DXA. Serum adipokines were
      measured using a Beadlyte assay. RESULTS: Two-factor ANOVA revealed significant
      treatment x genotype interactions for body fat (g), percent body fat, and serum
      leptin. The HF diet significantly increased body fat, percent body fat, and serum
      leptin in normal mice but not in myostatin-deficient mice. CONCLUSION: Loss of
      myostatin function not only increases muscle mass in animal models but also
      attenuates the body fat accumulation that usually accompanies an HF diet.

PMID- 16404406
TI  - Driving to work and overweight and obesity: findings from the 2003 New South
      Wales Health Survey, Australia.
AB  - OBJECTIVES: To examine possible associations between driving to work, physical
      activity and overweight and obesity. DESIGN: Secondary analysis of cross
      sectional data from a representative sample of the 2003 New South Wales Adult
      Health Survey, Australia. SUBJECTS: A total of 6810 respondents aged 16 years or
      over. MEASUREMENTS: Self-reported height and weight, modes of transport to work,
      level of physical activity, fruit and vegetable intake and social-economic
      status. RESULTS: Almost half of the respondents (49%) were overweight. The main
      mode of transport to work was driving a car (69%), 15% used public transport, 7%
      walked, 2% cycled and 6% worked at home. People who drove to work were less
      likely to achieve recommended levels of physical activity compared to non-car
      users (56.3 vs 44.3%, chi2 = 82.5, P<0.0001). Driving to work was associated with
      being overweight or obese (adjusted odds ratio = 1.13 (95% CI 1.01-1.27), P =
      0.047). Inadequate level of physical activity was independently associated with
      overweight or obesity. Socially and economically disadvantaged people were also
      more likely to be overweight and obese. In addition, being female or never
      married or having higher level of education was associated with a significantly
      reduced odds ratio of being overweight or obese, as was speaking a language other
      than English at home. No association was found between weight status and
      recommended vegetable or fruit intake. CONCLUSIONS: Driving to work is the
      dominant mode of commuting in a modern society and its impact on health requires
      scrutiny. The association found in this study between driving to work and
      overweight and obesity warrants further investigation to establish whether this
      relationship is causal. If proved as such, then promoting active transport modes
      such as walking, cycling and public transport should form a key component of
      global obesity prevention efforts.

PMID- 16404407
TI  - Influence of weight reduction by sibutramine on female sexual function.
AB  - BACKGROUND: It is well known that selective serotonin reuptake inhibitors (SSRIs)
      can cause sexual dysfunction, so it is possible that sibutramine, a serotonin and
      norepinephrine reuptake inhibitor, could induce sexual dysfunction. DESIGN AND
      SUBJECTS: The effect of sibutramine on sexual function was evaluated in 46
      overweight and obese (body mass index (BMI) > or = 23 kg/m2) but otherwise
      healthy married women (28-44 years). Participants were randomly assigned at
      baseline to either the sibutramine or control group. The Female Sexual Function
      Index (FSFI) questionnaire was used to assess sexual function at baseline and
      after treatment with behavioral therapy plus sibutramine 10 mg once daily or
      behavioral therapy alone (control) for 8 weeks. RESULTS: Mean weight loss from
      baseline to week 8 was -6.03% in sibutramine group and -0.38% in the control
      group. There was significant improvement of FSFI total score, arousal domain
      score and lubrication domain score in the sibutramine group (P<0.05), and
      significant differences in arousal, orgasm, satisfaction domain score and total
      score (P<0.05) in favor of sibutramine. Decreases in body weight and BMI were
      correlated with the improvement of arousal (r = -0.44 and r = -0.48,
      respectively) and orgasm (r = -0.45 and r = -0.46, respectively) domains.
      CONCLUSION: Treatment with sibutramine plus behavioral therapy did not induce
      sexual dysfunction and sibutramine-induced weight reduction appeared to have a
      positive impact on sexual function in this small group of overweight and
      moderately obese women. The degree of improvement in sexual function was
      correlated with the degree of weight reduction.

PMID- 16404408
TI  - Relationship between BMI, physical fitness, and motor skills in youth with mild
      intellectual disabilities.
AB  - INTRODUCTION: The negative impact of obesity on physical fitness and motor
      abilities has been documented in youth of various ages; however, this issue has
      not been explored in youth with mild intellectual disabilities (ID). Youth with
      ID are considered more overweight, less physically fit, and less motor proficient
      than peers without ID, so it is important to determine if these variables are
      associated in this population. The purpose of this study was to examine the
      relationship between body mass index (BMI), physical fitness, and motor skills in
      a large sample of youth with mild ID. METHOD: A systematic, stratified sampling
      method was used to select 444 youth with mild ID, aged 6-18 years, from eight
      special education schools in Hong Kong. Physical fitness was assessed using items
      from the national Hong Kong assessment: 6- (ages 6-8 years) or 9- (ages 9-18
      years) minute run, sit-up, isometric push-up, sit and reach, and sum of skinfold.
      Functional motor skills were assessed in 244 youth from the fitness sample using
      the Test of Gross Motor Development-II. Subjects were categorized into normal or
      overweight/obese BMI groups based on international cutoff points. RESULTS:
      Approximately 20% of the sample was classified as overweight/obese (average BMI
      normal = 17.47+/-2.69; overweight/obese = 24.78+/-4.05). ANCOVA controlling for
      age and gender revealed group differences in the run (P = 0.001) and push-ups (P
      = 0.05), but not in the motor or other fitness variables. After controlling for
      age and gender, BMI was correlated with the run (r = -0.27, P < 0.001) and push
      ups (r = -0.18, P = 0.008). Age and gender were entered as the first block in
      hierarchical regression and accounted for most of the variance in all dependent
      variables, except sit and reach. The inclusion of BMI in the second block added
      to the model for run and push-ups only (deltaR2 run = 0.04, push-ups = 0.03,
      P<0.001). CONCLUSION: Overweight/obesity is minimally associated with aerobic
      fitness and muscular strength in youth with mild ID. BMI did not impact other
      fitness measures (sit-up, sit and reach) or motor skills in the sample. The
      undesirable level of overweight/obesity in this sample requires increased
      attention and immediate intervention.

PMID- 16404409
TI  - Comparison of metabolic syndrome prevalence using six different definitions in
      overweight pre-pubertal children enrolled in a weight management study.
AB  - OBJECTIVES: To assess the implications of variation in Metabolic Syndrome (MS)
      definition (biochemical and anthropometric indicators) on MS prevalence estimates
      in a population of overweight and mildly obese children. DESIGN: Cross-sectional
      study. SUBJECTS: Ninety-nine (64 girls) overweight or mildly obese, but otherwise
      healthy, pre-pubertal 6-9-year olds recruited for a randomized controlled trial
      of weight management. MEASURES: Height, weight and waist circumference were
      measured with BMI and waist z-scores calculated. Fasting cholesterol and
      fractions, glucose and insulin were measured, together with systolic and
      diastolic blood pressure (BP). Anthropometric and metabolic indicators were
      classified as normal or elevated using adult- or child-specific cut points with
      clustering of MS indicators also assessed using two adult and three child
      specific definitions. RESULTS: A total of 0-4% of subjects were classified with
      MS when adult definitions were applied. This increased to between 39 and 60%
      using child-specific definitions, varying according to whether hyperinsulinaemia
      was central to the MS classification. Systolic BP, triglycerides, total
      cholesterol, high-density lipoprotein cholesterol and waist z-score increased
      across insulin quartiles (P<0.05). The use of body mass index and waist
      circumference in the MS definition classified the same subjects. CONCLUSIONS: The
      classification of MS in children depends strongly on the definition chosen, with
      MS prevalence estimates higher if insulin is part of the definition and child
      specific cut points for metabolic indicators are used. Hyperinsulinaemia and MS
      are common consequences of childhood obesity but they are not commonly part of
      the assessment or management plan for weight management in children. There is a
      need for the establishment of normal insulin ranges and consistent definition of
      MS in childhood and adolescence.

PMID- 16404410
TI  - Body mass index and all-cause mortality in a nationwide US cohort.
AB  - OBJECTIVE: To investigate whether the nature of the relationship between body
      mass index (BMI (kg/m2)) and all-cause mortality is direct, J- or U-shaped, and
      whether this relationship changes as people age. DESIGN: Prospective nationwide
      cohort study of US radiologic technologists (USRT). SUBJECTS: Sixty-four thousand
      seven hundred and thirty-three female and 19 011 male certified radiation
      technologists. METHODS: We prospectively followed participants from the USRT
      study who completed a mail survey in 1983-1989 through 2000. During an average of
      14.7 years of follow-up or 1.23 million person-years, 2278 women and 1495 men
      died. Using Cox's proportional-hazards regression analyses, we analyzed the
      relationship between BMI and all-cause mortality by gender and by age group (<55
      years; > or = 55 years). We also examined risk in never-smokers after the first 5
      years of follow-up to limit bias owing to the confounding effects of smoking and
      illness-related weight loss on BMI and mortality. RESULTS: Risks were generally J
      shaped for both genders and age groups. When we excluded smokers and the first 5
      year of follow-up, risks were substantially reduced in those with low BMIs. In
      never-smoking women under the age of 55 years (excluding the initial 5-year
      follow-up period), risk rose as BMI increased above 21.0 kg/m2, whereas in older
      women, risk increased beginning at a higher BMI (> or = 25.0 kg/m2). Among
      younger men who never smoked (excluding the initial 5-year follow-up period),
      risk began to rise above a BMI of 23.0 kg/m2, whereas in older men, risk did not
      begin to increase until exceeding a BMI of 30.0 kg/m2. CONCLUSIONS: In
      younger/middle-aged, but not older, women and men, mortality risks appear
      directly related to BMI. The more complicated relationship between BMI and
      mortality in older subjects suggests the importance of assessing whether other
      markers of body composition better explain mortality risk in older adults.

PMID- 16404411
TI  - Differential effects of exercise on body weight gain and adiposity in obesity
      prone and -resistant rats.
AB  - OBJECTIVE: To determine the effect of exercise on weight gain and adiposity in
      obesity-prone and -resistant rats. DESIGN: Body weight gain, fat pad weights,
      food intake, plasma leptin and insulin levels were assessed in outbred male
      Sprague-Dawley rats, which remained sedentary or were given unrestricted access
      to running wheels either before or after they developed diet-induced obesity
      (DIO) or diet-resistance (DR) on a high energy (HE; 31% fat) diet. RESULTS: When
      fed a low fat (4.5%) chow diet, rats which would later develop DIO (n=6) after 3
      weeks on HE diet ran the same amount as DR rats (n=6). Other rats were first made
      DIO (n=12) or DR (n=12) after 10 weeks on HE diet and then either kept sedentary
      or given running wheels for 4 weeks on HE diet. DIO and DR rats ran comparable
      amounts but only the DIO rats reduced their body weight gain, fat pad relative to
      body weights and plasma leptin levels significantly, compared to their sedentary
      controls. Exercise had no effect on food intake in either DIO or DR rats but
      reduced feed efficiency (weight gain/caloric intake) in both. CONCLUSION:
      Although DIO and DR rats ran similar amounts, the greater reduction in body
      weight gain and adiposity of exercising DIO rats suggests that they are more
      sensitive to some metabolic or physiologic system that prevents them from
      increasing their intake sufficiently to compensate for their net reduction in
      energy stores.

PMID- 16404412
TI  - Genetic variability and adaptive evolution in parthenogenetic root-knot
      nematodes.
AB  - Root-knot nematodes (RKN) of the genus Meloidogyne are biotrophic plant parasites
      of major agricultural importance, which exhibit very variable modes of
      reproduction, from classical amphimixis to mitotic parthenogenesis. This review
      focuses on those RKN species that reproduce exclusively by mitotic
      parthenogenesis (apomixis), in contrast to those that have meiotic/amphimitic
      events in their life cycle. Although populations of clonal organisms are often
      represented as being ecologically isolated and evolutionary inert, a considerable
      volume of literature provides evidence that asexual RKN are neither: they are
      widely distributed, extremely polyphagous, and amenable to selection and adaptive
      variation. The ancestors of the genus are unknown, but it is assumed that the
      parthenogenetic RKN have evolved from amphimictic species through hybridization
      and subsequent aneuploidization and polyploidization events. Molecular studies
      have indeed confirmed that the phylogenetic divergence between meiotic and
      mitotic RKN lineages occurred early, and have revealed an unexpected level of
      clonal diversity among populations within apomictic species. Laboratory
      experiments have shown that asexual RKN can rapidly adapt to new environmental
      constraints (eg host resistance), although with some fitness costs. Lastly, the
      molecular and chromosomal mechanisms that could contribute to genome plasticity
      leading to persistent genetic variation and adaptive evolution in apomictic RKN
      are discussed. It is concluded that RKN provide an excellent model system in
      which to study the dynamic nature and adaptive potential of clonal genomes.

PMID- 16404413
TI  - Quantitative trait loci for thermotolerance phenotypes in Drosophila
      melanogaster.
AB  - For insects, temperature is a major environmental variable that can influence an
      individual's behavioral activities and fitness. Drosophila melanogaster is a
      cosmopolitan species that has had great success in adapting to and colonizing
      diverse thermal niches. This adaptation and colonization has resulted in complex
      patterns of genetic variation in thermotolerance phenotypes in nature. Although
      extensive work has been conducted documenting patterns of genetic variation,
      substantially less is known about the genomic regions or genes that underlie this
      ecologically and evolutionarily important genetic variation. To begin to
      understand and identify the genes controlling thermotolerance phenotypes, we have
      used a mapping population of recombinant inbred (RI) lines to map quantitative
      trait loci (QTL) that affect variation in both heat- and cold-stress resistance.
      The mapping population was derived from a cross between two lines of D.
      melanogaster (Oregon-R and 2b) that were not selected for thermotolerance
      phenotypes, but exhibit significant genetic divergence for both phenotypes. Using
      a design in which each RI line was backcrossed to both parental lines, we mapped
      seven QTL affecting thermotolerance on the second and third chromosomes. Three of
      the QTL influence cold-stress resistance and four affect heat-stress resistance.
      Most of the QTL were trait or sex specific, suggesting that overlapping but
      generally unique genetic architectures underlie resistance to low- and high
      temperature extremes. Each QTL explained between 5 and 14% of the genetic
      variance among lines, and degrees of dominance ranged from completely additive to
      partial dominance. Potential thermotolerance candidate loci contained within our
      QTL regions are identified and discussed.

PMID- 16404414
TI  - Low maternal vitamin B12 status is associated with intrauterine growth
      retardation in urban South Indians.
AB  - OBJECTIVE: To assess the maternal sociodemographic, anthropometric, dietary and
      micronutrient status in apparently healthy pregnant women in order to determine
      their associations with intrauterine growth retardation (IUGR). DESIGN:
      Prospective observational study. SETTING: Bangalore City, India. SUBJECTS: A
      total of 478 women were recruited at 12.9+/-3.3 weeks of gestation and followed
      up at the first, second and third trimesters of pregnancy and at delivery. The
      dropout rate was 8.5%. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Birth weight
      was measured at hospital delivery. RESULTS: The mean birth weight was 2.85+/-0.45
      kg. In all, 28.6% of newborns were IUGR. There was a strong inverse relationship
      between maternal educational level and risk of IUGR. A low body weight at
      baseline was also associated with a high risk of IUGR. Compared with women in the
      highest quartile for second trimester weight gain, those in the lowest quartile
      had a significantly higher adjusted odds ratio (AOR: 3.98; 95% CI: 1.83, 8.65)
      for IUGR. Women in the lowest tertile for serum vitamin B(12) concentration
      during each of the three trimesters of pregnancy had significantly higher risk of
      IUGR (AOR: 5.98, 9.28 and 2.81 for trimesters 1-3, respectively). CONCLUSIONS:
      The present study demonstrates associations between educational status, maternal
      weight and gestational weight gain with IUGR. Importantly, in a subsample, there
      were strong associations of vitamin B(12) status with IUGR, suggesting that
      better socioeconomic conditions, improved nutritional status and early detection
      of vitamin B(12) deficiency in pregnancy combined with appropriate interventions
      are likely to play an important role in reducing IUGR.

PMID- 16404415
TI  - Safety aspects and cholesterol-lowering efficacy of low fat dairy products
      containing plant sterols.
AB  - OBJECTIVE: The aim of this study was to investigate whether a plant sterol
      mixture would reduce serum cholesterol when added to low fat dairy products in
      subjects with hypercholesterolaemia, and to examine the effects of the mixture on
      the serum plant sterol and fat-soluble vitamin levels. DESIGN: A parallel, double
      blind study. SETTING: The study was performed in three different locations in
      Finland. SUBJECTS: In total, 164 mildly or moderately hypercholesterolaemic
      subjects participated in the study. METHODS: The subjects were randomly divided
      into two groups: a plant sterol group and a control group. The subjects consumed
      the products for 6 weeks after a 3-week run-in period. The targeted plant sterol
      intake was 2 g/day in the sterol group. RESULTS: During the treatment period,
      there was a 6.5% reduction in serum total cholesterol in the sterol group while
      no change was observed in the control group (P<0.0005). Serum low-density
      lipoprotein (LDL) cholesterol was reduced by 10.4% in the sterol group and by
      0.6% in the control group (P<0.00005). There was no change during the trial in
      serum high-density lipoprotein (HDL) cholesterol or triacylglycerol
      concentrations. The HDL/LDL cholesterol ratio increased by 16.1% in the sterol
      group and by 4.3% in the control group (P=0.0001). Serum plant sterol levels
      increased significantly (P=0.0001) in the sterol group. None of the fat-soluble
      vitamin levels decreased significantly when changes in serum total cholesterol
      were taken into account. The hypocholesterolaemic effect of sterol administration
      was not influenced by apolipoprotein E phenotype. CONCLUSIONS: Yoghurt, low-fat
      hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced
      serum cholesterol in hypercholesterolaemic subjects and no adverse effects were
      noted in the dietary control of hypercholesterolaemia.

PMID- 16404417
TI  - Impact of familial risk factors on management and survival of early-onset breast
      cancer: a population-based study.
AB  - This population-based study evaluates the impact of a strong family history of
      breast cancer on management and survival of women with early-onset disease. We
      identified all breast cancer patients </=50 years, recorded between 1990 and 2001
      at the Geneva familial breast cancer registry. We compared patients at high
      familial risk and low familial risk in terms of tumour characteristics, method of
      detection, treatment, survival and breast cancer mortality risk. Compared to
      patients at low familial risk (n=575), those at high familial risk (n=58)
      received significantly more often systemic therapy, especially for node-negative
      or receptor-positive disease. Five-year disease-specific survival rates of
      patients at high vs low familial risk were 86 and 90%, respectively. After
      adjustment, there was no difference in breast cancer mortality in general. A
      strong family history nonsignificantly increased breast cancer mortality in
      patients </=40 years (adjusted hazard ratio (HR) 4.0, 95% CI 0.8-19.7) and in
      patients treated without chemotherapy (adjusted HR 2.7, 95% CI 0.6-12.5). A
      strong family history of breast cancer is associated with an increased use of
      systemic therapy in early-onset patients. Although a strong family history does
      not seem to affect survival in general, it may impair survival of very young
      patients and patients treated without adjuvant chemotherapy. Owing to the limited
      number of patients in this study, these results should be used only to generate
      hypotheses.

PMID- 16404418
TI  - Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1
      mutation carriers.
AB  - Deleterious mutations in the BRCA1 gene predispose women to an increased risk of
      breast and ovarian cancer. Many functional studies have suggested that BRCA1 has
      a role in DNA damage repair and failure in the DNA damage response pathway often
      leads to the accumulation of chromosomal aberrations. Here, we have compared
      normal lymphocytes with those heterozygous for a BRCA1 mutation. Short-term
      cultures were irradiated (8Gy) using a high dose rate and subsequently metaphases
      were analysed by 24-colour chromosome painting (M-FISH). We scored the
      chromosomal rearrangements in the metaphases from five BRCA1 mutation carriers
      and from five noncarrier control samples 6 days after irradiation. A
      significantly higher level of chromosomal damage was detected in the lymphocytes
      heterozygous for BRCA1 mutations compared with normal controls; the average
      number of aberrations per mitosis was 3.48 compared with 1.62 in controls
      (P=0.0001). This provides new evidence that heterozygous mutation carriers have a
      different response to DNA damage compared with noncarriers and that BRCA1 has a
      role in DNA damage surveillance. Our finding has implications for treatment and
      screening of BRCA1 mutation carriers using modalities that involve irradiation.

PMID- 16404419
TI  - BRAF mutations and phosphorylation status of mitogen-activated protein kinases in
      the development of flat and depressed-type colorectal neoplasias.
AB  - Although some molecular differences between flat-depressed neoplasias (FDNs) and
      protruding neoplasias (PNs) have been reported, it is uncertain if the BRAF
      mutations or the status of phosphorylated mitogen-activated protein kinase (p
      MAPK) are different between theses two groups. We evaluated the incidence of BRAF
      and KRAS mutations, high-frequency microsatellite instability (MSI-H), and the
      immunohistochemical status of p-MAPK in the nonserrated neoplasias (46 FDNs and
      57 PNs). BRAF mutations were detected in four FDNs (9%) and none of PNs (P=0.0369
      by Fisher's exact test). KRAS mutations were observed in none of FDNs and in 14
      PNs (25%; P=0.0002 by Fisher's exact test). MSI-H was detected in seven out of 44
      FDNs (16%) and in one out of 52 of PNs (2%) (P=0.022 by Fisher's exact test).
      Type B and C immunostaining for p-MAPK was observed in 34 out of 46 FDNs (72%),
      compared with 24 out of 55 PNs (44%; P=0.0022 by chi(2) test). There was no
      significant difference in the type B and C immunostaining of p-MAPK between FDNs
      with and without BRAF mutations. BRAF and KRAS mutations are mutually exclusive
      in the morphological characteristics of colorectal nonserrated neoplasia.
      Abnormal accumulation of p-MAPK protein is more likely to be implicated in the
      tumorigenesis of FDNs than of PNs. However, this abnormality in FDNs might occur
      via the genetic alteration other than BRAF or KRAS mutation.

PMID- 16404420
TI  - Disarming the guarded prognosis: predicting survival in newly referred patients
      with incurable cancer.
AB  - People affected by cancer want information about their prognosis but clinicians
      have trouble estimating and talking about it. We sought to determine the nature
      and accuracy of medical oncologists' estimates of life expectancy in newly
      referred patients with incurable cancer. With reference to each patient, medical
      oncologists estimated how long they thought 90, 50, and 10% of similar patients
      would live. These proportions were chosen to reflect worst case, predicted, and
      best case scenarios suitable for discussions. After a median follow-up of 35
      months, 86 of the 102 patients had died with an observed median survival of 12
      months. Oncologists' estimates of each patient's worst case, predicted and best
      case scenarios were well-calibrated: 10% of patients lived for fewer months than
      estimated for the worst 10% of similar patients; 50% lived for at least as long
      as estimated for 50% of similar patients (predicted survival), and 17% lived for
      more months than estimated for the best 10% of similar patients. Oncologists'
      estimates of each patient's predicted survival were imprecise: 29% were within
      0.67-1.33 times the patient's actual survival, 35% were too optimistic (>1.33
      times the actual survival), and 39% were too pessimistic (<0.67 times the actual
      survival). The proportions of patients with actual survival times bounded by
      simple multiples of their predicted survival were as follows: 61% between half to
      double their predicted, 6% at least three to four times their predicted, and 4%
      no more than 1/6 of their predicted; similar to the proportions in an exponential
      distribution (about 50%, 10% and 10% respectively). Ranges based on simple
      multiples of the predicted survival time appropriately convey prognosis and its
      uncertainty in newly referred people with incurable cancer.

PMID- 16404422
TI  - Human papilloma virus and breast cancer.

PMID- 16404421
TI  - mTOR signaling: implications for cancer and anticancer therapy.
AB  - Mounting evidence links deregulated protein synthesis to tumorigenesis via the
      translation initiation factor complex eIF4F. Components of this complex are often
      overexpressed in a large number of cancers and promote malignant transformation
      in experimental systems. mTOR affects the activity of the eIF4F complex by
      phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins. The
      immunosuppressant rapamycin specifically inhibits mTOR activity and retards
      cancer growth. Importantly, mutations in upstream negative regulators of mTOR
      cause hamartomas, haemangiomas, and cancers that are sensitive to rapamycin
      treatment. Such mutations lead to increased eIF4F formation and consequently to
      enhanced translation initiation and cell growth. Thus, inhibition of translation
      initiation through targeting the mTOR-signalling pathway is emerging as a
      promising therapeutic option.

PMID- 16404424
TI  - Characterisation of the GRAF gene promoter and its methylation in patients with
      acute myeloid leukaemia and myelodysplastic syndrome.
AB  - We report the isolation of the 5' flanking region of GRAF (GTPase regulator
      associated with the focal adhesion kinase), previously described as a putative
      tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic
      syndrome, and demonstrate its promoter activity in reporter gene assays. Two
      putative protein-binding sites are identified of which one was sensitive to CpG
      methylation. The suppressed GRAF expression could be restored in leukaemia cell
      lines by treatment with a demethylating agent and an inhibitor of histone
      deacetylases. In contrast to normal tissues, which tested negative for GRAF
      promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute
      myeloid leukaemia or myelodysplastic syndrome were positive.

PMID- 16404425
TI  - Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding
      mucosa.
AB  - The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is an RNA-binding
      protein involved in many processes that compose gene expression. K protein is
      upregulated in the malignant processes and has been shown to modulate the
      expression of genes involved in mitogenic responses and tumorigenesis. To explore
      the possibility that there are alternative isoforms of K protein expressed in
      colon cancer, we amplified and sequenced K protein mRNA that was isolated from
      colorectal cancers as well as from normal tissues surrounding the tumours.
      Sequencing revealed a single G-to-A base substitution at position 274 that was
      found in tumours and surrounding mucosa, but not in individuals that had no
      colorectal tumour. This substitution most likely reflects an RNA editing event
      because it was not found in the corresponding genomic DNAs. Sequencing of RNA
      from normal colonic mucosa of patients with prior resection of colorectal cancer
      revealed only the wild-type K protein transcript, indicating that G274A isoform
      is tumour related. To our knowledge, this is the first example of an RNA editing
      event in cancer and its surrounding tissue, a finding that may offer a new
      diagnostic and treatment marker.

PMID- 16404426
TI  - Polymorphisms of genes coding for insulin-like growth factor 1 and its major
      binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk:
      results from the EPIC study.
AB  - Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can
      enhance the development of tumours in different organs. Epidemiological studies
      have shown that an elevated level of circulating IGF-I is associated with
      increased risk of breast cancer, as well as of other cancers. Most of circulating
      IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth
      factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and
      IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I
      carriers may predict circulating levels of IGF-I and have an impact on cancer
      risk. We tested this hypothesis with a case-control study of 807 breast cancer
      patients and 1588 matched control subjects, nested within the European
      Prospective Investigation into Cancer and Nutrition. We genotyped 23 common
      single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured
      serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a
      weak but significant association of polymorphisms at the 5' end of the IGF1 gene
      with breast cancer risk, particularly among women younger than 55 years, and a
      strong association of polymorphisms located in the 5' end of IGFBP3 with
      circulating levels of IGFBP-3, which confirms previous findings. Common genetic
      variation in these candidate genes does not play a major role in altering breast
      cancer risk in Caucasians.

PMID- 16404427
TI  - Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent
      cellular cytotoxicity mechanism?
AB  - This study evaluated by immunohistochemistry (IHC) immune cell response during
      neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2
      positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast
      cancer were treated with trastuzumab plus docetaxel. Pathological complete and
      partial responses were documented for nine (39%) and 14 (61%) patients,
      respectively. Case-matched controls comprised patients treated with docetaxel
      based PST without trastuzumab (D; n=23) or PST without docetaxel or trastuzumab
      (non-taxane, non-trastuzumab, NT-NT; n=23). All surgical specimens were blind
      analysed by two independent pathologists, with immunohistochemical evaluation of
      B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells.
      Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression
      was also evaluated in residual tumour cells. Trastuzumab treatment was associated
      with significantly increased numbers of tumour-associated NK cells and increased
      lymphocyte expression of Granzyme B and TiA1 compared with controls. This study
      supports an in vivo role for immune (particularly NK cell) responses in the
      mechanism of trastuzumab action in breast cancer. These results suggest that
      trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially
      account for the synergistic activity of trastuzumab and docetaxel in breast
      cancer.

PMID- 16404428
TI  - Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact
      on energy metabolism.
AB  - Previously, renal cell carcinoma tissues were reported to display a marked
      reduction of components of the respiratory chain. To elucidate a possible
      relationship between tumourigenesis and alterations of oxidative phosphorylation,
      we screened for mutations of the mitochondrial DNA (mtDNA) in renal carcinoma
      tissues and patient-matched normal kidney cortex. Seven of the 15 samples
      investigated revealed at least one somatic heteroplasmic mutation as determined
      by denaturating HPLC analysis (DHPLC). No homoplasmic somatic mutations were
      observed. Actually, half of the mutations presented a level of heteroplasmy below
      25%, which could be easily overlooked by automated sequence analysis. The somatic
      mutations included four known D-loop mutations, four so far unreported mutations
      in ribosomal genes, one synonymous change in the ND4 gene and four nonsynonymous
      base changes in the ND2, COI, ND5 and ND4L genes. One renal cell carcinoma tissue
      showed a somatic A3243G mutation, which is a known frequent cause of MELAS
      syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episode)
      and specific compensatory alterations of enzyme activities of the respiratory
      chain in the tumour tissue. No difference between histopathology and clinical
      progression compared to the other tumour tissues was observed. In conclusion, the
      low abundance as well as the frequently observed low level of heteroplasmy of
      somatic mtDNA mutations indicates that the decreased aerobic energy capacity in
      tumour tissue seems to be mediated by a general nuclear regulated mechanism.

PMID- 16404429
TI  - Tumour budding at the deepest invasive margin correlates with lymph node
      metastasis in submucosal colorectal cancer detected by anticytokeratin antibody
      CAM5.2.
AB  - In the past few years, tumour budding at the invasive margin has been reported as
      a new risk factor for lymph node metastasis in advanced colorectal cancers, but
      it is sometimes difficult to detect tumour budding in submucosal colorectal
      cancer by haematoxylin and eosin staining. We immunohistochemically examined
      tumour budding at the deepest invasive margin of 56 surgically resected
      submucosal colorectal carcinomas using anticytokeratin antibody CAM5.2,
      furthermore checked by AE1/AE3, and determined the relation between tumour
      budding and clinicopathological factors. Moreover, we used the monoclonal
      antibody D2-40 for immunohistochemistry to detect lymphatic involvement. Tumour
      budding was detected in 42 cases (75.0%), and the budding-positive group showed a
      significantly higher rate of lymph node metastasis (including isolated tumour
      cells) (16/42 vs 0/14; P=0.004) than the budding-negative group. The sensitivity
      and negative predictive value of tumour budding alone for lymph node metastasis
      were superior to those of lymphatic invasion alone. Furthermore, the specificity
      and positive predictive value of the combination of either lymphatic invasion or
      tumour budding were superior to those of lymphatic invasion alone. Tumour budding
      detected immunohistochemically by using CAM5.2 is a newly found risk factor for
      lymph node metastasis and may help to avoid oversurgery in the future.

PMID- 16404430
TI  - PTEN activity could be a predictive marker of trastuzumab efficacy in the
      treatment of ErbB2-overexpressing breast cancer.
AB  - Trastuzumab is the only HER2/neu-directed therapy to have received Food and Drug
      Administration approval for the treatment of patients with metastatic breast
      cancer. The efficacy of trastuzumab depends on the HER2/neu status of the tumour
      and the patient's prior treatment, but even when patients are selected on the
      basis of HER2/neu gene amplification, the single-agent response rate ranges from
      12 to 30% and few patients respond to trastuzumab monotherapy. Here, we propose
      PTEN as a predictive biomarker for trastuzumab efficacy. Human breast cancer
      SKBR3 and drug-resistant SKBR3/R cells were investigated. We also examined
      clinical samples from patients who had been treated with trastuzumab and analysed
      the relationship between trastuzumab efficacy and PTEN level. The PI3K/Akt
      signalling pathway was observed to be highly active in the drug-resistant cells,
      and their level of PTEN was low. Delivery of antisense PTEN duplex siRNA
      significantly decreased the trastuzumab chemosensitivity of parental SKBR3 cells,
      and marked activation of Akt signalling pathway was also recognised. Moreover,
      immunohistochemical investigation revealed that trastuzumab treatment was
      remarkably successful in cells with elevated PTEN expression. Along with the
      immune-system-associated cytotoxic mechanism, several mechanisms have been
      proposed for the effect of trastuzumab. PTEN activity might play an important and
      major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful
      biomarker for predicting the efficacy of trastuzumab in the treatment of breast
      cancer.

PMID- 16404431
TI  - Changes in the serum proteome associated with the development of hepatocellular
      carcinoma in hepatitis C-related cirrhosis.
AB  - Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of
      effective therapies. The conventional serological diagnostic test, estimation of
      serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a
      screening tool and improved tests are needed to complement ultrasound scanning,
      the major modality for surveillance of groups at high risk of HCC. We have
      analysed the serum proteome of 182 patients with hepatitis C-induced liver
      cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of
      flight mass spectrometry (SELDI). The patients were split into a training set (84
      non-HCC, 60 HCC) and a 'blind' test set (21 non-HCC, 17 HCC). Neural networks
      developed on the training set were able to classify the blind test set with 94%
      sensitivity (95% CI 73-99%) and 86% specificity (95% CI 65-95%). Two of the SELDI
      peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC
      patients (P<0.001) and were identified as kappa and lambda immunoglobulin light
      chains. This approach may permit identification of several individual proteins,
      which, in combination, may offer a novel way to diagnose HCC.

PMID- 16404432
TI  - Evaluation of an inflammation-based prognostic score (GPS) in patients with
      metastatic breast cancer.
AB  - Prediction of outcome in patients with metastatic breast cancer remains
      problematical. The present study evaluated the value of an inflammation-based
      score (Glasgow Prognostic Score, GPS) in patients with metastatic breast cancer.
      The GPS was constructed as follows: patients with both an elevated C-reactive
      protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a score
      of 2. Patients in whom only one or none of these biochemical abnormalities was
      present were allocated a score of 1 or 0, respectively. In total, 96 patients
      were studied. During follow-up 51 patients died of their cancer. On multivariate
      analysis of the GPS and treatment received, only the GPS (HR 2.26, 95% CI 1.45
      3.52, P<0.001) remained significantly associated with cancer-specific survival.
      The presence of a systemic inflammatory response (the GPS) appears to be a useful
      indicator of poor outcome independent of treatment in patients with metastatic
      breast cancer.

PMID- 16404433
TI  - Evaluating the role of human papillomaviruses in conjunctival neoplasia.
AB  - Mucosal, cutaneous and Epidermodysplasia verruciformis (EV)-related human
      papillomaviruses (HPVs) were searched by broad-spectrum PCR in 86 conjunctival
      neoplasia biopsies and 63 conjunctival non-neoplastic control tissue from Ugandan
      subjects. Seven different EV-related HPV types, including a putative new HPV, and
      two mucosal HPVs were detected in 25% (14 out of 56) of HIV-positive, in 10%
      (three out of 30) of HIV-negative conjunctival neoplasia samples, and rarely (0
      1.6%) in control subjects. The absence of high-risk HPVs and the low detection
      frequency of EV-related HPV types in more advanced tumour stages (10%) raise
      doubts about their role in conjunctival carcinomas.

PMID- 16404434
TI  - Determination of TGFbeta1 protein level in human primary breast cancers and its
      relationship with survival.
AB  - Transforming growth factor-beta (TGFbeta)1 is thought to be implicated in breast
      cancer progression. However, data about the influence of TGFbeta1 on breast
      cancer development are conflicting. To clarify the clinical relevance of
      TGFbeta1, TGFbeta1 protein level has been measured by enzyme-immunoassay in 193
      breast tumour samples. We found that 94.3% of patients expressed TGFbeta1 with a
      range of 0-684 pg mg(-1) protein. In the overall population, an increase of
      tumoral TGFbeta1 was observed in premenopausal patients when compared to
      postmenopausal subgroup (P=0.0006). When patients were subdivided according to
      nodal status, TGFbeta1 was correlated to type-1 plasminogen activator inhibitor
      in the node-negative subgroup (P=0.040). Multivariate analysis revealed that,
      after lymph node status (P=0.0002) and urokinase-type plasminogen activator
      (P=0.004), TGFbeta1 was an independent prognostic marker for DFS (P=0.005) in the
      overall population. In the node-negative population, TGFbeta1 was the prominent
      prognostic factor (P=0.010). In the same population, Kaplan-Meier curves
      demonstrated that high TGFbeta1 level was correlated with a shorter disease-free
      survival (P=0.020). These data suggest that the measurement of tumoral TGFbeta1
      protein level, especially for node-negative patients, might help to identify a
      high-risk population early in tumour progression.

PMID- 16404435
TI  - Epigenetics provides a new generation of oncogenes and tumour-suppressor genes.
AB  - Cancer is nowadays recognised as a genetic and epigenetic disease. Much effort
      has been devoted in the last 30 years to the elucidation of the 'classical'
      oncogenes and tumour-suppressor genes involved in malignant cell transformation.
      However, since the acceptance that major disruption of DNA methylation, histone
      modification and chromatin compartments are a common hallmark of human cancer,
      epigenetics has come to the fore in cancer research. One piece is still missing
      from the story: are the epigenetic genes themselves driving forces on the road to
      tumorigenesis? We are in the early stages of finding the answer, and the data are
      beginning to appear: knockout mice defective in DNA methyltransferases, methyl
      CpG-binding proteins and histone methyltransferases strongly affect the risk of
      cancer onset; somatic mutations, homozygous deletions and methylation-associated
      silencing of histone acetyltransferases, histone methyltransferases and chromatin
      remodelling factors are being found in human tumours; and the first cancer-prone
      families arising from germline mutations in epigenetic genes, such as hSNF5/INI1,
      have been described. Even more importantly, all these 'new' oncogenes and tumour
      suppressor genes provide novel molecular targets for designed therapies, and the
      first DNA-demethylating agents and inhibitors of histone deacetylases are
      reaching the bedside of patients with haematological malignancies.

PMID- 16404436
TI  - Primary thromboprophylaxis for cancer patients with central venous catheters--a
      reappraisal of the evidence.
AB  - Venous thromboembolism (VTE) is responsible for an estimated 25 000 deaths per
      annum in UK hospital practice. It is well established that many of these deaths
      could be prevented through the use of appropriate thromboprophylaxis. This issue
      is of particular relevance in oncology practice, where the risks of VTE and
      bleeding are both significantly higher than those observed in general medical
      patients. Cancer patients with in-dwelling central venous catheters (CVCs) are at
      particularly high risk of developing thrombotic complications. However, the
      literature has produced conflicting conclusions regarding the efficacy of using
      routine primary thromboprophylaxis in these patients. Indeed such is the level of
      confusion around this topic, that the most recent version of the American College
      of Chest Physicians (ACCP) guidelines published in 2004 actually reversed their
      previous recommendation (published in 2001). Nevertheless, minidose warfarin
      continues to be routinely used in many oncology centres in the UK. In this
      article, we have performed a systematic review of the published literature
      regarding the efficacy and the risks, associated with using thromboprophylaxis
      (either minidose warfarin or low-dose LMWH) in cancer patients with CVC. On the
      basis of this evidence, we conclude that there is no proven role for using such
      thromboprophylaxis. However, asymptomatic CVC-related venous thrombosis remains
      common, and further more highly powered studies of better design are needed in
      order to define whether specific subgroups of cancer patients might benefit from
      receiving thromboprophylaxis.

PMID- 16404437
TI  - The anatomy and mechanisms of syndesmotic ankle sprains.
AB  - OBJECTIVE: To present a comprehensive review of the anatomy, biomechanics, and
      mechanisms of tibiofibular syndesmosis ankle sprains. DATA SOURCES: MEDLINE (1966
      1998) and CINAHL (1982-1998) searches using the key words syndesmosis,
      tibiofibular, ankle injuries, and ankle injuries-etiology. DATA SYNTHESIS:
      Stability of the distal tibiofibular syndesmosis is necessary for proper
      functioning of the ankle and lower extremity. Much of the ankle's stability is
      provided by the mortise formed around the talus by the tibia and fibula. The
      anterior and posterior inferior tibiofibular ligaments, the interosseous
      ligament, and the interosseous membrane act to statically stabilize the joint.
      During dorsiflexion, the wider portion anteriorly more completely fills the
      mortise, and contact between the articular surfaces is maximal. The distal
      structures of the lower leg primarily prevent lateral displacement of the fibula
      and talus and maintain a stable mortise. A variety of mechanisms individually or
      combined can cause syndesmosis injury. The most common mechanisms, individually
      and particularly in combination, are external rotation and hyperdorsiflexion.
      Both cause a widening of the mortise, resulting in disruption of the syndesmosis
      and talar instability. CONCLUSIONS AND RECOMMENDATION: Syndesmosis ankle injuries
      are less common than lateral ankle injuries, are difficult to evaluate, have a
      long recovery period, and may disrupt normal joint functioning. To effectively
      evaluate and treat this injury, clinicians should have a full understanding of
      the involved structures, functional anatomy, and etiologic factors.

PMID- 16404439
TI  - Leadership in the academy: junior faculty as program directors.

PMID- 16404438
TI  - Medical and orthopaedic conditions in special olympics athletes.
AB  - OBJECTIVE: Many Special Olympics athletes experience hypokinetic diseases and
      comorbid conditions that may predispose them to serious injuries during physical
      activity. A clear understanding of these conditions and diseases may assist
      health care professionals in preventing further distress and managing the
      injuries sustained by these athletes. Such diseases and conditions include
      overweight and obesity, diabetes, vision problems, seizure disorders, and Down
      syndrome, which is often associated with atlantoaxial instability. DATA SOURCES:
      MEDLINE, SPORT Discus, and Special Olympics information sources for the years
      1990-2000 using the key terms Special Olympics, mental retardation, comorbidity,
      Down syndrome, hypokinetic diseases, and physical activity were searched. DATA
      SYNTHESIS: A basic review of hypokinetic diseases and comorbid conditions
      prepares health care professionals for working with people with mental
      retardation. CONCLUSIONS AND RECOMMENDATIONS: Health care volunteers at Special
      Olympics events treat athletes with mental retardation who may also have some of
      the comorbid conditions and hypokinetic diseases observed commonly in this
      population. Moreover, many of these conditions and diseases are typical in
      athletes without mental retardation. Athletic trainers should be familiar with
      these conditions and diseases but should review the unique conditions and
      prescription medications commonly found in the Special Olympics population before
      providing medical services for these athletes.

PMID- 16404441
TI  - Leadership in the academy: junior faculty as program directors.

PMID- 16404440
TI  - Leadership in the academy: junior faculty as program directors.

PMID- 16404442
TI  - Leadership in the academy: junior faculty as program directors.

PMID- 16404444
TI  - Leadership in the academy: junior faculty as program directors.

PMID- 16404443
TI  - Leadership in the academy: junior faculty as program directors.

PMID- 16404445
TI  - Exercise and quadriceps muscle cooling time.
AB  - CONTEXT: Cryotherapy is commonly used for a variety of purposes; however, the
      body's response to cryotherapy immediately postexercise is unknown. OBJECTIVE: To
      investigate the effect of prior exercise on crushed-ice-bag treatment of a large
      muscle group. DESIGN: 2 x 3 repeated-measures design on depth (1 cm and 2 cm
      below adipose tissue) and treatment (exercise followed by ice, exercise followed
      by no ice, and no exercise followed by ice). SETTING: Sports Injury Research
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: Six physically active, uninjured male
      volunteers. INTERVENTION(S): For the 2 exercise conditions, subjects rode a
      stationary cycle ergometer at 70% to 80% of their age-predicted maximum heart
      rate, as calculated by the Karvonen method. For the no-exercise condition,
      subjects lay supine on a treatment table. The cryotherapy treatment consisted of
      a 1-kg ice bag applied to the anterior mid thigh. For the no-ice condition,
      subjects lay supine on a treatment table. MAIN OUTCOME MEASURE(S): Time required
      for the intramuscular temperatures at the 1-cm and 2-cm depths below adipose
      tissue to return to pre-exercise baseline and time required to cool the 1-cm and
      2-cm depths to 10 degrees C below the pre-exercise temperature. RESULTS: The time
      to cool the rectus femoris to the pre-exercise temperature using a crushed-ice
      bag treatment was reduced by approximately 40 minutes (P < .001). The ice bag
      cooled the 1-cm and 2-cm depths to the pre-exercise temperature within 7 minutes
      (P = .38), but the 2-cm tissue depth took nearly 13.5 minutes longer to cool than
      the 1-cm depth when no ice was applied (P = .001). The 1-cm depth cooled to 10
      degrees C below the pre-exercise temperature about 8 minutes sooner than the 2-cm
      depth, regardless of whether the tissue was exercised or not (P < .001). Exercise
      shortened the cooling time to 10 degrees C below the pre-exercise temperature by
      approximately 13 minutes (P = .05). CONCLUSIONS: Exercise before cooling with a
      crushed-ice bag enhanced the removal of intramuscular heat.

PMID- 16404446
TI  - Neoprene thigh sleeves and muscle cooling after exercise.
AB  - CONTEXT: Neoprene sleeves are alleged to increase heat in skeletal muscle, but no
      published research supports this belief. OBJECTIVES: To quantify anterior thigh
      skin and intramuscular temperature changes in varsity athletes wearing a neoprene
      thigh sleeve. DESIGN: A 2 x 2 x 3 x 5 factorial design with replicated measures
      on 3 variables. Independent variables included sex (male or female), neoprene
      sleeve (yes or no), exercise intensity (control, 50% intensity bicycle, 70%
      intensity bicycle), and exercise phase (5 minutes pre-exercise, 15 minutes of
      exercise, 0-10 minutes postexercise, 11-20 minutes postexercise, 21- 30 minutes
      postexercise). SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: 12
      male (23 +/- 0.95 years) and 12 female (20.59 +/- 1.44 years) National Collegiate
      Athletic Association Division I collegiate athletes actively engaged in offseason
      strength and conditioning programs. INTERVENTION(S): We sampled skin and muscle
      temperatures every 10 seconds for 50 minutes with a telethermometer interfaced to
      a personal computer. Each 60-minute session included 15 minutes pre-exercise
      (temperatures recorded during the last 5 minutes), 15 minutes of exercise
      (control, 50% intensity, and 70% intensity), and 30 minutes postexercise. Skin
      temperature was measured on the anterior aspect of the thigh using surface
      thermocouples. Intramuscular temperature was measured in the vastus lateralis
      muscle at a depth of 2 cm below the subcutaneous fat using implantable
      thermocouples. MAIN OUTCOME MEASURE(S): Skin and intramuscular temperature.
      RESULTS: Skin temperature was greater when subjects were wearing neoprene sleeves
      (1.4 degrees C during control, 3.1 degrees C during 70% exercise). Wearing a
      thigh sleeve had no effect on intramuscular temperature before or during
      exercise, but postexercise temperatures averaged 0.5 degrees C higher. Exercise
      intensity showed 1.3 degrees C to 2.0 degrees C increases in temperature with the
      sleeve. Females had higher intramuscular temperatures than males when wearing
      sleeves (1.4 degrees C during control, 1 degrees C during 50% exercise, and 0.8
      degrees C during 70% exercise). Males had higher skin temperatures than females
      (0.8 degrees C during 50% exercise, 1 degrees C during 70% exercise).
      CONCLUSIONS: Neoprene sleeves are effective in maintaining intramuscular
      temperature after 15 minutes of exercise and in increasing skin temperature
      during and after exercise. These results may be attributable to the insulating
      effects of the neoprene sleeve.

PMID- 16404447
TI  - Local ice-bag application and triceps surae muscle temperature during treadmill
      walking.
AB  - CONTEXT: Ice bags "to go" are a common practice in athletic training. OBJECTIVE:
      To determine the effect of submaximal exercise on tissue temperatures during a
      common ice-bag application. DESIGN: 2 X 5 fully repeated-measures design with
      treatment (cooling while resting, cooling while walking) and time (pretreatment,
      immediately after ice application, and at 10, 20, and 30 minutes during
      treatment) as the independent variables. SETTING: Laboratory setting. PATIENTS OR
      OTHER PARTICIPANTS: Sixteen healthy, physically active volunteers (age = 21.63 +/
      2.63 yrs, height = 68.97 +/- 4.00 cm, mass = 80.97 +/- 18.18 kg, calf skinfold =
      21.1 +/- 9.3 mm). MAIN OUTCOME MEASURE(S): Left triceps surae intramuscular and
      skin temperatures, as measured by thermocouples to the nearest 0.1 degrees C,
      served as dependent measures. INTERVENTION(S): After collecting baseline
      temperatures, we secured a 1.0-kg ice bag to the calf using plastic wrap before
      the subject either rested prone or walked on a treadmill at 4.5 km/h for 30
      minutes. RESULTS: Treatment did not (P < 0.10) affect the approximately 15
      degrees C (P < 0.0001) surface temperature decrease, which remained depressed
      immediately upon ice-bag application (P < 0.05). Conversely, intramuscular
      temperature continually cooled (34 to 28 degrees C), while subjects rested (P <
      0.0001), whereas no change took place during walking (P = 0.49). Moreover, at the
      20- and 30-minute treatment intervals, the resting intramuscular temperatures
      were, respectively, 3.9 degrees C and 5.4 degrees C cooler than the walking
      intramuscular temperatures (P < 0.01). CONCLUSIONS: The current trend of wrapping
      "to go" ice bags to the leg is not likely to achieve deep tissue cooling despite
      surface temperature decreases.

PMID- 16404448
TI  - An 18-day stretching regimen, with or without pulsed, shortwave diathermy, and
      ankle dorsiflexion after 3 weeks.
AB  - CONTEXT: The amount of retained ankle flexibility gains and the effects of
      diathermy on those gains are unclear. OBJECTIVE: To determine the retention of
      flexibility 3 weeks after an 18-day stretching regime and the effect of pulsed,
      shortwave diathermy on that retention. DESIGN: We used a 2x4 factorial with
      repeated measures on day (1, 19, 24, and 39). The other independent variable was
      treatment (stretch only versus diathermy and stretch). The dependent variable was
      ankle-dorsiflexion angular displacement as measured on a digital inclinometer.
      SETTING: Therapeutic Modality Research Laboratory. PATIENTS OR OTHER
      PARTICIPANTS: 23 healthy college-aged volunteers (8 males, 15 females; age = 22.7
      +/- 2.1 years, height = 171.1 +/- 8.8 cm, mass = 70.4 +/- 13.5 kg).
      INTERVENTIONS: All subjects performed 3 weeks (not including weekends) of low
      load, prolonged, long-duration stretching. One group performed stretching only;
      the other group also received diathermy. MAIN OUTCOME MEASURE(S): After an 18-day
      stretching regime and 7-day retention study, subjects returned 14 days later for
      the 3-week retention measure. The angle of inclination from the posterior
      Achilles tendon to the sole of the shoe near the heel was measured on each
      treatment and test day. RESULTS: Regardless of group (F(1,21) = 0.74, P = 0.40),
      the flexibility gained between days 1 (99.7 +/- 4.0 degrees), 19 (102.9 +/- 5.8
      degrees), and 24 (105.0 +/- 6.2 degrees) were maintained at day 39 (104.8+/- 7.2
      degrees) (P < .05). CONCLUSIONS: Flexibility gains in normal ankles with 3 weeks
      of training were retained for at least 3 weeks after training ceased. The
      application of pulsed, shortwave diathermy during stretching did not appear to
      influence the chronic retention of flexibility gains in normal subjects.

PMID- 16404449
TI  - A methodologic approach for the comparison between dynamic contractions:
      influences on the neuromuscular system.
AB  - CONTEXT: Although isotonic and isokinetic exercises are commonly used in sports
      medicine and rehabilitation, studies comparing their effects on the neuromuscular
      system have provided conflicting results. OBJECTIVE: To compare responses of the
      neuromuscular system to isotonic and isokinetic contractions by controlling the
      total external amount of work performed and the mean angular movement velocity.
      DESIGN: A familiarization session was followed by isotonic and isokinetic
      sessions of tests performed on an isokinetic dynamometer. Each subject
      participated in 3 sessions. SETTING: A sport sciences research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Nine healthy adult males with no history of knee
      injury. INTERVENTION(S): The isotonic session consisted of 3 sets of 8 knee
      extensions at 80% of each subject's maximal voluntary isotonic contraction. The
      isokinetic session involved 3 sets of n knee extensions at a preset velocity
      equivalent to the mean velocity measured during the corresponding isotonic sets;
      n represented the number of repetitions subjects had to achieve to equalize the
      total external amount of work performed during the corresponding isotonic sets.
      MAIN OUTCOME MEASURE(S): We recorded mechanical parameters, n, and surface
      electromyographic signals from the vastus medialis, rectus femoris, and vastus
      lateralis muscles. Then root mean square, mean power frequency, and neuromuscular
      efficiency values were calculated for each repetition. RESULTS: As expected, the
      total external amount of work and mean angular velocity were similar between the
      isotonic and isokinetic sessions. The number of repetitions performed was
      equivalent in both sessions. In addition, although no "shift" of mean power
      frequency occurred, mean neuromuscular efficiency decreased linearly with
      repetitions for both modes in no differentiated way. CONCLUSIONS: Standardization
      of isotonic and isokinetic contractions based on total external amount of work
      and movement velocity is possible. This method can be applied by future
      investigators aiming to compare chronic effects of these 2 contraction modes on
      the neuromuscular system.

PMID- 16404450
TI  - Dehydration and symptoms of delayed-onset muscle soreness in hyperthermic males.
AB  - CONTEXT: Exercise in the heat produces cellular conditions that may leave
      skeletal muscle susceptible to exercise-induced microdamage. Delayed-onset muscle
      soreness (DOMS) is a clinical model of contraction-induced skeletal muscle
      injury. OBJECTIVE: To determine whether thermoregulation during exercise heat
      stress adversely affects muscle injury and the accompanying DOMS. DESIGN:
      Randomized group test-retest design. SETTING: Laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Ten healthy male volunteers were randomly assigned to either the
      euhydration/hyperthermic or dehydration/hyperthermic group. INTERVENTION(S):
      Participants were randomly assigned to treadmill walking in a hot, humid
      environmental chamber (40 degrees C and 75% relative humidity) with either oral
      rehydration (euhydration/hyperthermic) or fluid restriction
      (dehydration/hyperthermic). Immediately after heat exposure and while
      hyperthermic, participants performed an eccentrically biased downhill run to
      induce DOMS. MAIN OUTCOME MEASURE(S): We measured DOMS characteristics pre
      exercise and at 0.5, 24, 48, 72, and 96 hours postexercise. RESULTS: Treadmill
      exercise and exposure to the hot ambient environment elicited a 0.9% body mass
      loss for the euhydrated/ hyperthermic (mean rectal temperature after 60 minutes
      of heat-stress trial = 38.2 +/- 0.4 degrees C) and 3.3% body mass loss for the
      dehydrated/hyperthermic participants (mean rectal temperature after 60 minutes of
      heat-stress trial = 38.1 +/- 0.4 degrees C). Quadriceps perceived pain was
      significantly higher (F(5,40) = 18.717, P <or= .001) than baseline at 24 and 48
      hours postexercise, following the classic pattern of DOMS. Overall lower
      extremity perceived pain was significantly higher for the
      dehydration/hyperthermia group than the euhydration/hyperthermia group (F(1,8) =
      6.713, P = .032). Punctate tenderness of the vastus lateralis for the
      dehydration/hyperthermic group was 6.9% higher (F(5,40) = 4.462, P = .003) than
      for the euhydration/ hyperthermic group. No clinically important findings were
      revealed for passive range of motion for knee flexion. For both groups,
      quadriceps isometric strength (F(5,40) = 12.924, P <or= .001) was 17.5% and 20.0%
      lower at 0.5 hours postexercise than at 72 and 96 hours postexercise,
      respectively. Further, quadriceps isometric strength remained 10.5% reduced at 24
      hours postexercise compared with 96 hours postexercise. CONCLUSIONS: Skeletal
      muscle microdamage, indirectly evidenced by DOMS, was exacerbated in hyperthermic
      participants dehydrated by exercise in a hot ambient environment. Individuals
      performing novel exercise, particularly with a significant eccentric component,
      should use caution when training in a hot, humid environment and implement
      frequent rest and rehydration breaks.

PMID- 16404451
TI  - Single-leg jump-landing stabilization times in subjects with functionally
      unstable ankles.
AB  - CONTEXT: Factors contributing to functional ankle instability may cause
      individuals with the condition to land from a jump differently than those with
      stable ankles. OBJECTIVE: To determine stabilization time differences during
      single-leg jump landings between stable and unstable ankle groups and to report
      the reliability and precision of time-to-stabilization measures. DESIGN: A mixed
      design with 1 between factor (ankle group) and 1 within factor (direction) was
      used to analyze the comparison between our 10 subjects with functional ankle
      instability and 10 subjects with stable ankles. Time to stabilization (seconds)
      was the dependent measure. Reliability for time-to-stabilization measures of our
      12 additional subjects with stable ankles were assessed using intraclass
      correlation coefficients (ICC 2,7). Standard errors of measurements were also
      calculated for time-to-stabilization measures. SETTING: Sports medicine research
      laboratory. PATIENTS OR OTHER PARTICIPANT(S): Ten subjects with functional ankle
      instability who reported at least 2 sprains and "giving way'' sensations at their
      ankles constituted the functional ankle instability group. Ten subjects without a
      history of ankle sprain injury served as healthy subjects. Twelve additional
      healthy subjects participated in the reliability study. INTERVENTION(S): Subjects
      performed a jump-landing test, which required them to jump 50% to 55% of their
      maximum vertical jump height and then land on a single leg on a force plate.
      After landing, they stabilized quickly and remained as motionless as possible in
      a single-leg stance for 20 s. MAIN OUTCOME MEASURE(S): Anterior-posterior and
      medial/ lateral vibration magnitude curve fit time-to-stabilization. RESULTS:
      Time to stabilization was longer for the functional ankle instability group (1.98
      +/- 0.81 s) than for the stable ankle group (1.45 +/- 0.30 s) (P < .05).
      Reliability (standard error of the measurement) values for anterior/posterior and
      medial/lateral time-to-stabilization were 0.79 (0.15 s) and 0.65 (0.26 s),
      respectively. CONCLUSIONS: Time to stabilization was longer for subjects with
      functional ankle instability than subjects with stable ankles. The ankle
      instability may have impaired the subjects' ability to stabilize after a single
      leg jump landing. Reliabilities and standard errors of the measurements of time
      to-stabilization measures were moderate and low, respectively.

PMID- 16404452
TI  - A new force-plate technology measure of dynamic postural stability: the dynamic
      postural stability index.
AB  - CONTEXT: New measures of dynamic postural stability are needed to address
      weaknesses of previous measures. OBJECTIVE: To assess the feasibility,
      reliability, and precision of a new measure of dynamic postural stability.
      DESIGN: A single within-subjects design was used to determine optimal sampling
      interval as well as intersession reliability. SETTING: Biomechanics laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Eighteen subjects (7 men [age = 22 +/- 3 years,
      height = 175 +/- 5 cm, mass = 75 +/- 16 kg] and 11 women [age = 23 +/- 2 years,
      height = 163 +/- 6 cm, mass = 68 +/- 13 kg]) without lower extremity impairment.
      INTERVENTION(S): A jump protocol that required subjects to perform a 2-legged
      jump to a height equivalent to 50% of their maximum vertical leap and land on a
      single leg. MAIN OUTCOME MEASURE(S): The Dynamic Postural Stability Index (DPSI)
      and the directional components (medial-lateral, anterior-posterior, and vertical)
      after a jump landing. RESULTS: We observed a significant sampling-interval main
      effect (F(2,51) = 26.88, P < .01) for the DPSI; the 10-second trial duration
      produced significantly smaller means than the 5- and 3-second trial durations,
      whereas the 5-second trial result was also significantly smaller than that of the
      3-second trial. The DPSI was highly reliable between test sessions (intraclass
      correlation coefficient = .96) and very precise (SEM = .03). CONCLUSIONS: These
      results suggest that the DPSI can be used in conjunction with a functional single
      leg hop stabilization test and is a reliable and precise measure of dynamic
      postural stability. We believe the shortest sampling interval (3 seconds) is the
      best choice for studying and mimicking athletic performance as closely as
      possible.

PMID- 16404453
TI  - Resistance training and head-neck segment dynamic stabilization in male and
      female collegiate soccer players.
AB  - CONTEXT: Cervical resistance training has been purported to aid in reducing the
      severity of brain injuries in athletes. OBJECTIVE: To determine the effect of an
      8-week resistance-training program on head-neck segment dynamic stabilization in
      male and female collegiate soccer players. DESIGN: Pretest and posttest control
      group design. SETTING: University research laboratory and fitness center.
      PATIENTS OR OTHER PARTICIPANTS: Thirty-six National Collegiate Athletic
      Association Division I collegiate soccer players (17 men, 19 women).
      INTERVENTION(S): The resistance training group underwent an 8-week cervical
      resistance training program that consisted of 3 sets of 10 repetitions of neck
      flexion and extension at 55% to 70% of their 10-repetition maximum 2 times a
      week. Participants in the control group performed no cervical resistance
      exercises. MAIN OUTCOME MEASURE(S): Head-neck segment kinematics and stiffness,
      electromyographic activity of the upper trapezius and sternocleidomastoid muscles
      during force application to the head, and neck flexor and extensor isometric
      strength. RESULTS: No kinematic, electromyographic, or stiffness training effects
      were seen. The posttest resistance training group isometric neck flexor strength
      was 15% greater than the pretest measurement. Isometric neck extensor strength in
      the female resistance training group was 22.5% greater at the posttest than at
      the pretest. Women's neck girth increased 3.4% over time regardless of training
      group level. Women exhibited 7% less head-neck segment length and 26% less head
      neck segment mass than men. CONCLUSIONS: Despite increases in isometric strength
      and girth, the 8-week isotonic cervical resistance training did not enhance head
      neck segment dynamic stabilization during force application in collegiate soccer
      players. Future researchers should examine the effect of head-neck segment
      training protocols that include traditional and neuromuscular activities (eg,
      plyometrics) with the focus of reducing head acceleration on force application.

PMID- 16404454
TI  - Current trends in athletic training practice for concussion assessment and
      management.
AB  - CONTEXT: Athletic trainers surveyed in 1999 demonstrated little consensus on the
      use of concussion grading scales and return-to-play criteria. Most relied on
      clinical examination or symptom checklists to evaluate athletes with concussion.
      OBJECTIVE: To investigate the current trends of certified athletic trainers in
      concussion assessment and management. DESIGN: Subjects were invited to
      participate in a 32-question Internet survey. SETTING: An Internet link to the
      survey was e-mailed to the subjects. PATIENTS OR OTHER PARTICIPANTS: A total of
      2750 certified athletic trainers and members of the National Athletic Trainers'
      Association were randomly e-mailed and invited to participate. MAIN OUTCOME
      MEASURE(S): Survey questions addressed topics including years of certification,
      number of concussions evaluated each year, methods of assessing concussion, and
      guidelines used for return to play. Compliance with the recent position statement
      of the National Athletic Trainers' Association on sport-related concussion was
      also evaluated. RESULTS: Certified athletic trainers averaged 9.9 +/- 7.3 years
      of certification and evaluated an average of 8.2 +/- 6.5 concussions per year. To
      assess concussion, 95% reported using the clinical examination, 85% used symptom
      checklists, 48% used the Standardized Assessment of Concussion, 18% used
      neuropsychological testing, and 16% used the Balance Error Scoring System. The
      most frequently used concussion grading scale and return-to-play guideline
      belonged to the American Academy of Neurology (30%). When deciding whether to
      return an athlete to play, certified athletic trainers most often used the
      clinical examination (95%), return-to-play guidelines (88%), symptom checklists
      (80%), and player self-report (62%). The most important tools for making a return
      to-play decision were the clinical examination (59%), symptom checklists (13%),
      and return-to-play guidelines (12%). Only 3% of certified athletic trainers
      surveyed complied with the recent position statement, which advocated using
      symptom checklists, neuropsychological testing, and balance testing for managing
      sport-related concussion. CONCLUSIONS: Our findings suggest that only a small
      percentage of certified athletic trainers currently follow the guidelines
      proposed by the National Athletic Trainers' Association. Various assessment
      methods and tools are currently being used, but clinicians must continue to
      implement a combination of methods and tools in order to comply with the position
      statement.

PMID- 16404455
TI  - Importance and applicability of approved clinical instructor standards and
      criteria to certified athletic trainers in different clinical education settings.
AB  - CONTEXT: For optimal clinical education of athletic training students, Clinical
      Instructor Educators and program directors need to proactively select, train, and
      evaluate their Approved Clinical Instructors (ACIs). OBJECTIVE: To assess the
      relative importance and applicability of ACI standards to certified athletic
      trainers employed in different athletic training clinical education settings.
      DESIGN: Respondents rated and ranked the importance and applicability of the 7
      standards presented by Weidner and Henning. Crucial standards to warrant dropping
      an ACI from the clinical education program were also listed. SETTING: Mailed
      questionnaire. PATIENTS OR OTHER PARTICIPANTS: A total of 55 program directors
      invited their ACIs, representing different types of clinical settings, to
      complete the questionnaire. Of the 399 ACIs who responded, 30 (8%) worked in
      clinics, 50 (13%) in high schools, and 319 (79%) in colleges or universities.
      MAIN OUTCOME MEASURE(S): We compared the mean scores of the importance and
      applicability ratings and rankings by employment setting. Chi-square analyses
      were calculated to measure associations between employment settings and whether a
      standard was crucial. Respondents' comments were also assessed. RESULTS: No
      significant differences were noted among employment settings for overall
      importance and applicability ratings. A difference was seen for only
      interpersonal relationships, with clinic and high school respondents giving this
      standard higher importance and applicability ratings than college/university
      respondents. No associations were shown between the settings and whether a
      standard was marked as crucial. The importance of a standard and barriers to
      implementing a standard (particularly ACI role strain) were the most common
      themes. CONCLUSIONS: The Weidner and Henning standards are considered to be
      important and applicable across a variety of athletic training clinical education
      settings. Legal and ethical behavior was considered the most crucial standard.
      The ACIs seemed to be encountering role strain in their dual roles as clinicians
      and clinical instructors, a problem warranting further investigation.

PMID- 16404456
TI  - Competing perspectives during organizational socialization on the role of
      certified athletic trainers in high school settings.
AB  - CONTEXT: When certified athletic trainers (ATCs) enter a workplace, their
      potential for professional effectiveness is affected by a number of factors,
      including the individual's ability to put acquired knowledge, skills, and
      attitudes into practice. This ability may be influenced by the preconceived
      attitudes and expectations of athletes, athletes' parents, athletic directors,
      physical therapists, physicians, and coaches. OBJECTIVE: To examine the
      perspectives of high school coaches and ATCs toward the ATC's role in the high
      school setting by looking at 3 questions: (1) What are coaches' expectations of
      ATCs during different phases of a sport season? (2) What do ATCs perceive their
      role to be during different phases of a season? and (3) How do coaches'
      expectations compare with ATCs' expectations? DESIGN: Qualitative research design
      involving semistructured interviews. SETTING: High schools. PATIENTS OR OTHER
      PARTICIPANTS: Twenty high school varsity basketball coaches from 10 high schools
      in 2 states and the ATCs assigned to these teams. MAIN OUTCOME MEASURE(S): For
      the coaches, 12 questions focused on 3 specific areas: (1) the athletic training
      services they received as high school basketball coaches, (2) each coach's
      expectations of the ATC with whom he or she was working during various phases of
      the season, and (3) coaches' levels of satisfaction with the athletic training
      services provided to their team. For the ATCs, 17 questions focused on 3 areas:
      (1) the ATC's background, (2) the ATC's perceived duties at different phases of
      the basketball season and his or her relationship with the coach, and (3) other
      school factors that enhanced or interfered with the ATC's ability to perform
      duties. RESULTS: Three themes emerged. Coaches had limited knowledge and
      understanding of ATCs' qualifications, training, professional preparation, and
      previous experience. Coaches simply expected ATCs to be available to complement
      their roles. Positive communication was identified as a critical component to a
      good coach-ATC relationship. CONCLUSIONS: Although all participants valued good
      communication, poor communication appeared to limit ATCs' contributions to player
      performance beyond simple availability. Coaches must be educated by ATCs to
      ensure they are receiving qualified athletic training support.

PMID- 16404457
TI  - A systematic review of the effects of therapeutic taping on patellofemoral pain
      syndrome.
AB  - OBJECTIVE: To investigate the efficacy of patellar taping on pain control,
      patellar alignment, and neuromuscular control (ie, vastus medialis oblique
      activation, knee extensor moment, etc) in subjects with patellofemoral pain
      syndrome. DATA SOURCES: We searched MEDLINE, SPORT Discus, PEDro, and CINAHL
      through December 2004, using the key words patellar taping, therapeutic taping,
      McConnell taping, taping, chronic injury, patellofemoral pain, and knee. STUDY
      SELECTION: Criteria for inclusion criteria were studies that exclusively
      recruited patients diagnosed with patellofemoral pain syndrome or anterior knee
      pain and outcome measures specific to pain reduction, neuromuscular control, and
      patellar positioning. DATA EXTRACTION: We identified and reviewed 16 studies with
      an average PEDro score of 4.25/10. Articles were divided into 3 categories based
      on primary outcome measures: 4 randomized controlled trials on treatment methods
      and pain, 9 studies on neuromuscular control, and 3 on patellar positioning. DATA
      SYNTHESIS: Although patellar taping seems to reduce pain and improve function in
      people with patellofemoral pain syndrome during activities of daily living and
      rehabilitation exercise, strong evidence to identify the underlying mechanisms is
      still not available.

PMID- 16404458
TI  - Recognition and treatment of muscle dysmorphia and related body image disorders.
AB  - OBJECTIVE: To present the reader with various psychobehavioral characteristics of
      muscle dysmorphia, discuss recognition of the disorder, and describe treatment
      and referral options. DATA SOURCES: We conducted a comprehensive review of the
      relevant literature in CINAHL, MEDLINE, SPORT Discus, EBSCO, PsycINFO, and
      PubMed. All years from 1985 to the present were searched for the terms muscle
      dysmorphia, bigorexia, and reverse anorexia. DATA SYNTHESIS: The incidence of
      muscle dysmorphia is increasing, both in the United States and in other regions
      of the world, perhaps because awareness and recognition of the condition have
      increased. Although treatment options are limited, therapy and medication do
      work. The primary issue is identifying the disorder, because it does not present
      like other psychobehavioral conditions such as anorexia or bulimia nervosa. Not
      only do patients see themselves as healthy, most look very healthy from an
      outward perspective. The causes of muscle dysmorphia are not well understood,
      which reinforces the need for continued investigation. CONCLUSIONS: Muscle
      dysmorphia is an emerging phenomenon in society. Pressure on males to appear more
      muscular and lean has prompted a trend in the area of psychobehavioral disorders
      often likened to anorexia and bulimia nervosa. Athletes are particularly
      susceptible to developing body image disorders because of the pressures
      surrounding sport performance and societal trends promoting muscularity and
      leanness. Health care professionals need to become more familiar with the common
      signs and symptoms of muscle dysmorphia, as well as the treatment and referral
      options, in order to assist in providing appropriate care. In the future, authors
      should continue to properly measure and document the incidence of muscle
      dysmorphia in athletic populations, both during and after participation.

PMID- 16404459
TI  - Celiac disease in an elite female collegiate volleyball athlete: a case report.
AB  - OBJECTIVE: To present the case of an elite female volleyball player who
      complained of diarrhea and fatigue after preseason training. BACKGROUND: The
      athlete lost 8.1 kg during the first 20 days of training, and we initially
      suspected an eating disorder. The sports medicine team interviewed the athlete
      and found she did not have psychological symptoms indicative of an eating
      disorder. The results of routine blood tests revealed critically high platelet
      counts; in conjunction with the physical findings, the athlete was referred to a
      gastroenterologist. DIFFERENTIAL DIAGNOSIS: Our initial suggestion was an eating
      disorder. Therefore, the differential diagnosis included anorexia athletica,
      anorexia nervosa, and bulimia nervosa. On referral, the differential diagnosis
      was anemia, gastrointestinal dysfunction, lymphoma, or bowel adenocarcinoma.
      Diarrhea, weight loss, and blood test results were suggestive of active celiac
      disease, and a duodenal biopsy specimen confirmed this diagnosis. TREATMENT: The
      athlete was treated with a gluten-free diet, which excludes wheat, barley, and
      rye. Dietary substitutions were incorporated to maintain adequate caloric intake.
      UNIQUENESS: The presence of active celiac disease may not be uncommon. However,
      elite athletes who face celiac disease present a new challenge for the athletic
      trainer. The athletic trainer can help guide the athlete in coping with the
      lifestyle changes associated with a gluten-free diet. CONCLUSIONS: One in every
      200 to 400 individuals has celiac disease; many of these individuals are
      asymptomatic and, therefore, their conditions are undiagnosed. Undiagnosed,
      untreated celiac disease and patients who fail to follow the gluten-free diet
      increase the risk of further problems.

PMID- 16404460
TI  - Celiac disease symptoms in a female collegiate tennis player: a case report.
AB  - OBJECTIVE: To present the case of a collegiate tennis player with celiac disease
      symptoms. BACKGROUND: Celiac disease is a common intestinal disorder that is
      often confused with other conditions. It causes severe intestinal damage
      manifested by several uncomfortable signs and symptoms. Failure by the sports
      medicine staff to recognize symptoms consistent with celiac disease and treat
      them appropriately can have deleterious consequences for the athlete.
      DIFFERENTIAL DIAGNOSIS: Irritable bowel syndrome, Crohn disease, Addison disease,
      lupus erythematosus, juvenile rheumatoid arthritis, lactose intolerance, herpes
      zoster, psychogenic disorder (depression), fibromyalgia, complex regional pain
      syndrome, hyperthyroidism, anemia, type I diabetes. TREATMENT: The athlete
      underwent a series of blood and allergen tests to confirm or refute a diagnosis
      of celiac disease. When celiac disease was suspected, dietary modifications were
      made to eliminate all wheat-based and gluten-based products from the athlete's
      diet. UNIQUENESS: The athlete was able to fully compete in a competitive National
      Collegiate Athletic Association Division I tennis program while experiencing the
      debilitating effects associated with celiac disease. The immediacy of symptom
      onset was notable because the athlete had no history of similar complaints.
      CONCLUSIONS: Celiac disease is a potentially life-threatening condition that
      affects more people than reported. A properly educated sports medicine staff can
      help to identify symptoms consistent with celiac disease early, so damage to the
      intestine is minimized. Prompt recognition and appropriate management allow the
      athlete to adjust the diet accordingly, compete at a high-caliber level, and
      enjoy a healthier quality of life.

PMID- 16404461
TI  - Proceedings, 105th Annual Meeting Medical Library Association, Inc. San Antonio,
      Texas May 14-19, 2005.

PMID- 16404464
TI  - Defining the informationist: a case study from the Frederick L. Ehrman Medical
      Library.

PMID- 16404466
TI  - Strengthening professionals: a chapter-level formative evaluation of the Medical
      Library Association mentoring initiative.
AB  - OBJECTIVE: The main objective was to determine to what extent the Medical Library
      Association (MLA) mentoring initiative was implemented in the South Central
      Chapter of the Medical Library Association (SCC/ MLA) and to identify the needs,
      improvements, and adjustments in mentoring services for the future to improve the
      practice of librarianship. METHODS: The data were collected by administering an
      anonymous structured survey designed by the authors. The survey was mailed to all
      335 chapter members. The authors elicited responses to determine the chapter
      members' mentoring needs, awareness of available resources, satisfaction with
      existing services and resources, needs for the future, and suggestions to meet
      those needs. DISCUSSION: Of the 335 delivered surveys, 184 were returned,
      yielding a return rate of 55%. Eighty percent had a mentor or mentors in their
      careers, and 74% were either very satisfied or satisfied with the relationship.
      The majority considered having a mentor a critical part of the professional
      experience. The mentoring activity chosen by respondents as the most important
      was improvement of job performance through skills development. Over 50% were
      aware of SCC/MLA's mentoring activities, and less than 50% were aware of MLA's
      mentoring Website. CONCLUSIONS: The rate of response and the wealth of comments
      provided by respondents document the high level of interest in mentoring by
      medical librarians in the region. The following mentoring services were equally
      important to SCC/MLA members and were recommended for improvement or development
      at the regional level: a formalized mentoring program in the region, Web-based
      mentoring resources on the SCC/MLA Website, and a continuing education course for
      mentors. Members are aware of mentoring activities in the region; however,
      participation levels need to be increased in activities that SCC/MLA and MLA
      provide. Mentoring continues to evolve as a service in the profession.

PMID- 16404465
TI  - The Medical Library Association's professional development program: a look back
      at the way ahead.
AB  - OBJECTIVE: Reflecting patterns evident in past Janet Doe Lectures, the 2005
      address reviews the Medical Library Association's (MLA's) professional
      development activities from their beginnings after World War II. A group of
      related but separate activities is traced through the establishment of an
      integrated professional development program. A further objective is to introduce
      newer members of MLA to their heritage and to remind others how the association
      has reached this point in its history. SETTING: The lecture provides an overview
      of the evolution of MLA's professional development program-with emphasis on
      certification and continuing education in the early years. It further reflects
      briefly on some of the more recent MLA activities that have greatly impacted
      professional development and underscores some new initiatives. ANALYSIS: The
      efforts of a virtual who's who of MLA's membership have been responsible for the
      convergence of the association's efforts over more than half a century to provide
      a comprehensive professional development program. As a participant in MLA's
      professional development activities for more than forty years, the 2005 lecturer
      provides a personal view of the growth and expansion of the program. CONCLUSIONS:
      Professional development has been a hallmark of MLA for many years. The
      association's challenge is to continue to develop creative and innovative
      programs, to continuously review and revise existing programs, and to have the
      vision and vitality to maintain a viable program that will provide the membership
      with the knowledge and skills needed to function effectively now and in the
      future.

PMID- 16404467
TI  - The MedlinePlus public user interface: studies of design challenges and
      opportunities.
AB  - QUESTION: What are the challenges involved in designing, modifying, and improving
      a major health information portal that serves over sixty million page views a
      month? SETTING: MedlinePlus, the National Library of Medicine's (NLM's) consumer
      health Website, is examined. METHOD: Challenges are presented as six "studies,"
      which describe selected design issues and how NLM staff resolved them. MAIN
      RESULT: Improving MedlinePlus is an iterative process. Changes in the public user
      interface are ongoing, reflecting Web design trends, usability testing
      recommendations, user survey results, new technical requirements, and the need to
      grow the site in an orderly way. CONCLUSION: Testing and analysis should
      accompany Website design modifications. New technologies may enhance a site but
      also introduce problems. Further modifications to MedlinePlus will be informed by
      the experiences described here.

PMID- 16404468
TI  - Developing optimal search strategies for detecting clinically sound treatment
      studies in EMBASE.
AB  - OBJECTIVE: The ability to accurately identify articles about therapy in large
      bibliographic databases such as EMBASE is important for researchers and
      clinicians. Our study aimed to develop optimal search strategies for detecting
      sound treatment studies in EMBASE in the year 2000. METHODS: Hand searches of
      journals were compared with retrievals from EMBASE for candidate search
      strategies. Six trained research assistants reviewed fifty-five journals indexed
      in EMBASE and rated articles using purpose and quality indicators. Candidate
      search strategies were developed for identifying treatment articles and then
      tested, and the retrievals were compared with the hand-search data. The operating
      characteristics of the strategies were calculated. RESULTS: Three thousand eight
      hundred fifty articles were original studies on treatment, of which 1,256 (32.6%)
      were methodologically sound. Combining search terms revealed a top performing
      strategy (random:.tw. OR clinical trial:.mp. OR exp health care quality) with
      sensitivity of 98.9% and specificity of 72.0%. Maximizing specificity, a top
      performing strategy (double-blind:.mp. OR placebo:.tw. OR blind: .tw.) achieved a
      value over 96.0%, but with compromised sensitivity at 51.7%. A 3-term strategy
      achieved the best optimization of sensitivity and specificity (random:.tw. OR
      placebo:.mp. OR double-blind:.tw.), with both these values over 92.0%.
      CONCLUSION: Search strategies can achieve high performance for retrieving sound
      treatment studies in EMBASE.

PMID- 16404469
TI  - Information-seeking behavior and use of information resources by clinical
      research coordinators.
AB  - PURPOSE: The study sought to understand the literature searching experiences and
      skills of clinical research coordinators at a large academic medical center.
      SETTING/PARTICIPANTS/RESOURCES: The Health Sciences Library System, University of
      Pittsburgh, conducted a survey of clinical research coordinators at the
      University of Pittsburgh and the University of Pittsburgh Medical Center to
      solicit their perceived use and knowledge of the library's electronic resources.
      BRIEF DESCRIPTION: The University of Pittsburgh Institutional Review Board (IRB)
      is a "high volume IRB" that monitors human subject research at both the
      University of Pittsburgh and the University of Pittsburgh Medical Center. More
      than 3,500 human research studies and clinical trials are active at any given
      time. Many studies entail more than minimal risk to human subjects, with the
      majority evaluating or including a drug or medical device. Clinical research
      coordinators are involved in most of these studies or trials. Their roles and
      responsibilities focus on managing many aspects of the study or clinical trial.
      As a first step in understanding the literature searching experiences and skills
      of these research coordinators, baseline data were gathered from this group in
      November 2004. RESULTS/OUTCOME: The data from this survey indicate that clinical
      research coordinators are a population who would benefit from training by
      academic medical center librarians in how to use electronic library resources and
      services. EVALUATION METHOD: A Web-based survey solicited participants'
      information (gender, education, job title) and role in the IRB process (job
      responsibilities, number studies they manage). The majority of the survey
      questions focused on the use of specific electronic library resources, the type
      of information wanted, and the types of problems encountered.

PMID- 16404471
TI  - Developing a virtual community for health sciences library book selection:
      Doody's Core Titles.
AB  - PURPOSE: The purpose of this article is to describe Doody's Core Titles in the
      Health Sciences as a new selection guide and a virtual community based on an
      effective use of online systems and to describe its potential impact on library
      collection development. SETTING/PARTICIPANTS/RESOURCES: The setting is the
      availability of health sciences selection guides. Participants include Doody
      Enterprise staff, Doody's Library Board of Advisors, content specialists, and
      library selectors. Resources include the online system used to create Doody's
      Core Titles along with references to complementary databases. BRIEF DESCRIPTION:
      Doody's Core Titles is described and discussed in relation to the literature of
      selection guides, especially in comparison to the Brandon/Hill selected lists
      that were published from 1965 to 2003. Doody's Core Titles seeks to fill the
      vacuum created when the Brandon/Hill lists ceased publication. Doody's Core
      Titles is a unique selection guide based on its method of creating an online
      community of experts to identify and score a core list of titles in 119 health
      sciences specialties and disciplines. RESULTS/OUTCOME: The result is a new
      selection guide, now available annually, that will aid health sciences librarians
      in identifying core titles for local collections. EVALUATION METHOD: Doody's Core
      Titles organizes the evaluation of core titles that are identified and
      recommended by content specialists associated with Doody's Book Review Service
      and library selectors. A scoring mechanism is used to create the selection of
      core titles, similar to the star rating system employed in other Doody Enterprise
      products and services.

PMID- 16404470
TI  - How do primary care physicians seek answers to clinical questions? A literature
      review.
AB  - OBJECTIVES: The authors investigated the extent to which changes occurred between
      1992 and 2005 in the ways that primary care physicians seek answers to clinical
      problems. What search strategies are used? How much time is spent on them? How do
      primary care physicians evaluate various search activities and information
      sources? Can a clinical librarian be useful to a primary care physician? METHODS:
      Twenty-one original research papers and three literature reviews were examined.
      No systematic reviews were identified. RESULTS: Primary care physicians seek
      answers to only a limited number of questions about which they first consult
      colleagues and paper sources. This practice has basically not changed over the
      years despite the enormous increase in and better accessibility to electronic
      information sources. One of the major obstacles is the time it takes to search
      for information. Other difficulties primary care physicians experience are
      related to formulating an appropriate search question, finding an optimal search
      strategy, and interpreting the evidence found. Some studies have been done on the
      supporting role of a clinical librarian in general practice. However, the effects
      on professional behavior of the primary care physician and on patient outcome
      have not been studied. A small group of primary care physicians prefer this
      support to developing their own search skills. DISCUSSION: Primary care
      physicians have several options for finding quick answers: building a question
      and-answer database, consulting filtered information sources, or using an
      intermediary such as a clinical librarian.

PMID- 16404472
TI  - A review of electronic journal acquisition, management, and use in health
      sciences libraries.
AB  - PURPOSE: The paper describes patterns of electronic journal usage in health
      sciences libraries during the past decade. METHOD: The paper presents a case
      study, documenting the pattern of acquisition, management, and usage at the Louis
      Calder Memorial Library of the University of Miami Miller School of Medicine.
      RESULTS: Health sciences journals were early to offer electronic alternatives to
      print. As a result, health sciences libraries, their patrons, and the public at
      large were early to embrace the new versions and continue to embrace the
      significant changes in scholarly communication they enable. Although the patterns
      of electronic journals among health sciences libraries and other special and
      academic libraries have similarities, they also have differences. Broad studies
      of electronic journals in non-health sciences libraries have been published, but
      a retrospective review of electronic journals in health sciences libraries has
      not.

PMID- 16404473
TI  - Online medical books: their availability and an assessment of how health sciences
      libraries provide access on their public Websites.
AB  - OBJECTIVE: The objective of this study was to determine the number and topical
      range of available online medical books and to assess how health sciences
      libraries were providing access to these resources on their public Websites.
      METHOD: The collection-based evaluative technique of list checking was used to
      assess the number and topical range of online medical books of the six largest
      publishers. Publisher inventory lists were downloaded over a two-day period (May
      16-17, 2004). Titles were counted and compared with the 2003 Brandon/Hill list. A
      sample of health sciences libraries was subsequently derived by consulting the
      2004 "Top Medical Schools-Research" in U.S. News & World Report. Bibliographic
      and bibliothecal access methods were evaluated based on an inspection of the
      publicly available Websites of the sample libraries. RESULTS: Of 318 currently
      published online medical books, 151 (47%) were Brandon/Hill titles covering 42 of
      59 Brandon/Hill topics (71%). These 151 titles represented 22% (N = 672) of the
      Brandon/Hill list, which further broke down as 52 minimal core, 41 initial
      purchase, and 58 other recommended Brandon/Hill titles. These numbers represented
      50%, 28%, and 12%, respectively, of all Brandon/Hill titles corresponding to
      those categories. In terms of bibliographic access, 20 of 21 of sampled libraries
      created catalog records for their online medical books, 1 of which also provided
      analytical access at the chapter level, and none provided access at the chapter
      section level. Of the 21 libraries, 19 had library Website search engines that
      provided title-level access and 4 provided access at the chapter level and none
      that at the chapter section level. For bibliothecal access, 19 of 21 libraries
      provided title-level access to medical books, 8 of which provided classified and
      alphabetic arrangements, 1 provided a classified arrangement only, and 10
      provided an alphabetic arrangement only. No library provided a bibliothecal
      arrangement for medical book chapters or chapter sections. CONCLUSIONS: This
      study shows that the number and topical range of online medical books is reaching
      a point where collection-level consideration is warranted to facilitate efficient
      use and to prevent the problem of split files. However, the results also show
      that few efforts are underway on the publicly available Websites of the surveyed
      health sciences libraries to provide the analytical access necessary to meet the
      structural needs of clinical information seekers.

PMID- 16404474
TI  - Exploring the roles of librarians and health care professionals involved with
      complementary and alternative medicine.
AB  - OBJECTIVES: The researcher conducted qualitative research about the role of
      health care professionals and librarians involved with complementary and
      alternative medicine (CAM). The goals were to identify resources these
      professionals use to explore the librarians' role as well as their approaches to
      teaching and searching with respect to CAM, to acquire information about CAM
      education, and to connect with other librarians in the CAM field. METHODS: Semi
      structured interviews with open-ended questions were used. RESULTS: Sixteen
      health care and information professionals from ten different institutions in
      Boston, Baltimore, and Calgary were interviewed. Major themes from the interviews
      were: CAM funding, integration of CAM and conventional medicine, roles of
      librarians, "hot" CAM issues, and information access. Information about four
      aspects of CAM education--technology, undergraduate, graduate, and continuing--is
      presented. A wealth of information resources was identified. CONCLUSIONS: A CAM
      librarian's role is unique; many specialize in specific areas of CAM, and
      opportunities exist for librarians to partner with CAM groups. CAM information
      professionals' major roles involve information access and retrieval and
      education. Further study is required concerning CAM consumer health, integrative
      CAM and conventional medicine models, and the librarian's role in a CAM
      environment. CAM funding is a major concern.

PMID- 16404475
TI  - Nonhomologous end-joining deficiency of L5178Y-S cells is not associated with
      mutation in the ABCDE autophosphorylation cluster.
AB  - Cells with mutated autophosphorylation sites in the ABCDE cluster of DNA
      dependent protein kinase catalytic subunit (DNA-PKcs) are defective in the repair
      of ionising radiation-induced DSB, but show in an in vitro test the same DNA-PK
      activity as the cells possessing wild type enzyme. Nevertheless, the mutated DNA
      PK is able to undergo ATP-dependent autophosphorylation and inactivation. This
      characteristics correspond well with the phenotypic features of the L5178Y-S (LY
      S) cell line that is defective in DSB repair, shows a pronounced G1 phase
      radiosensitivity, but in which the level of DNA-PK activity present in total cell
      extracts is similar to that of its radioresistant counterpart L5178Y-R (LY-R)
      cell line. The purpose of this work was to examine the possible alterations in
      the sequence encoding the cluster of autophosphorylation sites in the DNA
      dependent protein kinase in LY-S cells. Despite the presence of phenotypic
      features indicating the possibility of such alterations, no differences were
      found between the sequences coding for the autophosphorylation sites in L5178Y-R
      and L5178Y-S cells. In conclusion, the repair defect in LY-S cells is not related
      to the structure of the DNA-PK autophosphorylation sites (ABCDE casette).

PMID- 16404476
TI  - Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and
      hepatocellular carcinoma.
AB  - We investigated glutathione level, activities of selenium independent GSH
      peroxidase, selenium dependent GSH peroxidase, GSH S-transferase, GSH reductase
      and the rate of lipid peroxidation expressed as the level of malondialdehyde in
      liver tissues obtained from patients diagnosed with cirrhosis or hepatocellular
      carcinoma. GSH level was found to be lower in malignant tissues compared to
      adjacent normal tissues and it was higher in cancer than in cirrhotic tissue. Non
      Se-GSH-Px activity was lower in cancer tissue compared with adjacent normal liver
      or cirrhotic tissue, while Se-GSH-Px activity in cancer was found to be similar
      to its activity in cirrhotic tissue and lower compared to control tissue. An
      increase in GST activity was observed in cirrhotic tissue compared with cancer
      tissue, whereas the GST activity in cancer was lower than in adjacent normal
      tissue. The activity of GSH-R was similar in cirrhotic and cancer tissues, but
      higher in cancer tissue compared to control liver tissue. An increased level of
      MDA was found in cancer tissue in comparison with control tissue, besides its
      level was higher in cancer tissue than in cirrhotic tissue. Our results show that
      the antioxidant system of cirrhosis and hepatocellular carcinoma is severely
      impaired. This is associated with changes of glutathione level and activities of
      GSH-dependent enzymes in liver tissue. GSH and enzymes cooperating with it are
      important factors in the process of liver diseases development.

PMID- 16404477
TI  - Nonviral transfection of human umbilical cord blood dendritic cells is feasible,
      but the yield of dendritic cells with transgene expression limits the application
      of this method in cancer immunotherapy.
AB  - Dendritic cells (DC) generated from human umbilical cord blood might replace
      patients' DC in attempts to elicit tumor-specific immune response in cancer
      patients. We studied the efficiency of transfection of human cord blood DC with
      plasmid DNA carrying the enhanced version of green fluorescent protein (EGFP) as
      a reporter gene, to test if nonviral gene transfer would be a method to load DC
      with protein antigens for immunotherapy purposes. Cord blood mononuclear cells
      were cultured in serum-free medium in the presence of granulocyte-monocyte colony
      stimulating factor (GM-CSF), stem cell factor (SCF) and Flt-3 ligand (FL), to
      generate DC from their precursors, and thereafter transfected by electroporation.
      Maturation of DC was induced by stimulation with GM-CSF, SCF, FL and phorbol
      myristate acetate (PMA). Transfected DC strongly expressed EGFP, but transfection
      efficiency of DC, defined as HLA-DR(+) cells lacking lineage-specific markers,
      did not exceed 2.5%. Expression of the reporter gene was also demonstrated in the
      DC generated from transfected, purified CD34(+) cord blood cells, by stimulation
      with GM-CSF, SCF, FL, and tumor necrosis factor alpha (TNF-alpha). Transfection
      of CD34(+) cells was very efficient, but proliferation of the transfected cells
      was much reduced as compared to the untransfected cells. Therefore, the yield of
      transgene-expressing DC was relatively low. In conclusion, nonviral transfection
      of cord blood DC proved feasible, but considering the requirements for
      immunotherapy in cancer patients, transfection of differentiated DC or generation
      of DC from transfected hematopoietic stem cells provide only a limited number of
      DC expressing the transgene.

PMID- 16404479
TI  - Leptin and cardiovascular diseases.
AB  - Although obesity is strongly associated with cardiovascular disease (CVD), the
      endogenous relationship between obesity and CVD is still not fully clear.
      Emerging evidence from both animal and human studies indicates that leptin may
      play an important role in obesity-related CVD. Besides modulating appetite and
      metabolism, leptin has also been shown to increase sympathetic nerve activity,
      stimulate generation of reactive oxygen species, upregulate endothelin-1
      production and potentiate platelet aggregation. These effects of leptin may
      contribute to hypertension, endothelial dysfunction and atherosclerosis in obese
      individuals. Better understanding the mechanisms of leptin resistance should
      facilitate therapeutic approaches to reverse the phenomenon of selective leptin
      resistance. These recent discoveries could lead to novel strategies for treatment
      of obesity-associated CVD.

PMID- 16404478
TI  - Interaction of anthracene and its oxidative derivatives with human serum albumin.
AB  - Binding affinities of ten polycyclic aromatic hydrocarbons to albumin were
      determined: anthracene, its eight oxy-derivatives: anthraquinone, 9
      anthracenemethanol, 9-anthraldehyde, 9-anthracenecarboxylic acid, 1,4
      dihydroxyanthraquinone, 1,5-dihydroxyanthraquinone, 1,8-dihydroxyanthraquinone,
      2,6-dihydroxyanthraquinone and benzo[a]pyrene. The quenching of albumin
      fluorescence was used to measure the PAH - protein interaction. The theoretical
      curve of calculated fluorescence was fitted to experimental data after necessary
      corrections regarding PAHs fluorescence and inner filter effect. From the
      numerical fitting the final association constants were calculated. Anthracene and
      anthraquinone failed to quench the albumin fluorescence. 9-anthracenecarboxylic
      acid showed the highest, while 9-anthracenemethanol the weakest albumin binding
      affinity. The affinity constants determined for 9-anthraldehyde and
      benzo[a]pyrene were of the same magnitude and indicated low-affinity binding to
      albumin. The constants obtained for the four dihydroxyanthraquinones were higher,
      but dissimilar, which suggests that the position of the functional group in
      anthracene molecule influences the binding constant. Moreover, this study
      suggests that the type of substituent plays a significant role in PAH-albumin
      complex formation. The carboxylic group increases the binding affinity of the
      anthracene molecule the most rather than the presence of both carbonyl and
      hydroxyl groups. The lowest affinity constants were obtained for aldehyde, methyl
      and carbonyl substituents.

PMID- 16404480
TI  - Update on heart disease therapies: a report from the 2005 scientific sessions of
      the American Heart Association.

PMID- 16404481
TI  - Leptin as a common link to obesity and hypertension.
AB  - Leptin is a recently isolated circulating peptide hormone that is primarily
      synthesized and secreted by adipocytes. One of the major functions of this
      hormone is the control of energy balance by binding to receptors in the
      hypothalamus, leading to reduction in food intake, elevation in temperature and
      energy expenditure. In addition, increasing evidence suggests that leptin,
      through both direct and indirect actions, may play an important role in
      cardiovascular and renal functions. While the relevance of endogenous leptin
      needs further clarification, it appears to be a potential pressure- and volume
      regulating factor, and may function pathophysiologically as a common link to
      obesity and hypertension.

PMID- 16404482
TI  - Antibiotic therapy for coronary heart disease: the myth and the reality.
AB  - Atherosclerosis is acknowledged as an active inflammatory and thrombotic disease,
      as opposed to simple degeneration. Infection with microorganisms may contribute
      to this inflammation and hence the atherosclerotic process. The "infective"
      hypothesis - first proposed more than a century ago by Virchow - has been
      revisited in recent years and has implicated numerous microorganisms as potential
      stimuli. The greatest body of evidence points to Chlamydia pneumoniae, a
      respiratory pathogen, as the "culprit" microorganism. Consistent finding of
      bacterial antigens, DNA and occasionally live "viable" organisms within human
      atherosclerotic plaque support the evidence for the concept linking C. pneumoniae
      to atherosclerosis. Although original seroepidemiological studies indicated an
      association, more recent prospective and larger studies suggest that there may be
      only a weak link between elevated antibodies and immune complexes to C.
      pneumoniae and coronary heart disease (CHD). Animal models have shown how
      atherogenesis can be induced by endovascular infection with C. pneumoniae; in
      vitro studies have explored various immunological and inflammatory pathways
      linking infection and atherothrombosis. On the basis of this, antibiotic trials
      have been explored to assess whether there is any role for antichlamydial agents
      in the treatment of cardiovascular events. Here, we focus on the main antibiotic
      studies and explores patient criteria and choice, duration of therapy, and
      whether effects on clinical events could be reduced.

PMID- 16404483
TI  - The intrinsic nanofibrillar morphology of polyaniline.
AB  - Polyaniline nanofibers are shown to form spontaneously during the chemical
      oxidative polymerization of aniline. The nanofibrillar morphology does not
      require any template or surfactant, and appears to be intrinsic to polyaniline
      synthesized in water. Two approaches--interfacial polymerization and rapidly
      mixed reactions--have been developed to prepare pure nanofibers. The key is
      suppressing the secondary growth that leads to agglomerated particles. The
      effects of different dopant acids and solvents are discussed. Changing the dopant
      acid can be used to tune the diameters of the nanofibers between about 30 and 120
      nm. Changing the organic solvent in interfacial polymerization reactions has
      little effect on the product. A brief discussion of the processibility of the
      nanofibers is presented. The possibility of creating nanofibrillar structures for
      selected polyaniline derivatives is also demonstrated.

PMID- 16404485
TI  - Highly active heterogeneous Fenton catalyst using iron oxide nanoparticles
      immobilized in alumina coated mesoporous silica.
AB  - A highly active heterogeneous Fenton catalyst was fabricated by impregnating iron
      oxide nanoparticles in alumina coated mesoporous SBA-15 silica.

PMID- 16404484
TI  - Fabrication of TiO2 using L-lysine-based organogelators as organic templates:
      control of the nanostructures.
AB  - Using uncharged or negatively charged L-lysine-based organogelators as templates,
      the nanostructures of TiO2 are controllable.

PMID- 16404487
TI  - [The German Medical Association support initiative on health care research].
AB  - The 108th German Medical Assembly adopted a 6-year support initiative for health
      care research in order to contribute to the further development of this young
      scientific discipline which has not yet been sufficiently established in Germany.
      The program is focussed on the following subjects: (1) influence of economic
      changes on outpatient and inpatient medical care, (2) implementation of medical
      guidelines in medical routine and (3) the physician factor. Setting methodical
      standards in this new field and opening up access to medical data should provide
      a relevant impulse to health care research in Germany. The promoting strategy of
      the German Medical Association will be completed by initiating a network of
      scientists, research promoters and health care players.

PMID- 16404489
TI  - Biomaterial-dependent MMP-2 expression in fibroblasts from patients with
      recurrent incisional hernias.
AB  - With regard to the pathogenesis of recurrent incisional hernia, an impaired
      connective tissue quality leading to an aberrant scarring process has been
      proposed. For the matrix metalloproteinase (MMP-2) a pathogenetic involvement in
      direct inguinal hernia development is reported. With mesh implantation as the
      gold standard treatment for incisional hernias, the aim of the present study was
      to investigate the MMP-2 expression in patients with recurrent incisional hernias
      with and without mesh-materials. In primary fibroblast cultures obtained from
      skin scars in patients with and without recurrent incisional hernias, MMP-2
      synthesis and gene expression were investigated. Furthermore, MMP-2 synthesis and
      gene expression of fibroblasts were compared after incubation with two different
      mesh materials: polypropylene and absorbable polyglactin filaments. MMP-2 enzyme
      activity was determined by semiquantitative zymography and mRNA synthesis by
      quantitative RT-PCR. Both MMP-2 enzyme activity and mRNA expression were similar
      in hernia and control fibroblasts in vitro. In control fibroblasts mesh
      incubation did not significantly affect MMP-2 expression, whereas polypropylene
      mesh contact of fibroblasts from patients with recurrent incisional hernias led
      to a major decrease of MMP-2 activity and of mRNA expression. In the absence of
      biomaterials fibroblasts from recurrent incisional hernia, patients have no
      alterations of their MMP-2 synthesis compared to control fibroblasts, whereas a
      specific response was found after biomaterial contact hereby indicating
      differences in fibroblast phenotype.

PMID- 16404490
TI  - Inguinal hernia recurrence: classification and approach.
AB  - We reviewed case reports, updated to January 2005, of 2,468 operations for groin
      hernia in 2,350 patients, including 277 recurrent hernias. The data obtained,
      following a simple anatomo-clinical classification into three types that could be
      used to orient surgical strategy, were: type R1--first recurrence of "high"
      oblique external reducible hernia with small (<2 cm) defect in non-obese patients
      after pure tissue or mesh repair; type R2--first recurrence of "low" direct
      reducible hernia with small (<2 cm) defect in non-obese patients after pure
      tissue or mesh repair; and type R3--all other recurrences, including femoral
      recurrences, recurrent groin hernia with large defect (inguinal eventration),
      multi-recurrent hernias, non-reducible contralateral primary or recurrent hernia,
      and situations compromised by aggravating factors (e.g. obesity) or otherwise not
      easily included in R1 or R2 after pure tissue or mesh repair.

PMID- 16404491
TI  - Characterization of the structure and properties of authentic and counterfeit
      polypropylene surgical meshes.
AB  - A counterfeit version of the Ethicon Prolene polypropylene mesh was distributed
      to hospitals and clinics and unintentionally implanted into patients undergoing
      tension-free hernia repair. On December 19, 2003, the Food and Drug
      Administration (FDA) issued a public health web notification indicating that the
      counterfeit mesh was not sterile or safe to use. To develop safety
      recommendations for patients with the counterfeit mesh implant, we compared the
      counterfeit's structural, physical, chemical and mechanical properties with
      polypropylene meshes previously cleared by FDA. The mesh fibers for all the
      products tested were found to have similar chemical and physical properties. The
      mechanical properties were directly related to the knitted structure (loop size,
      repeat distance, fabric tightness) and the porosity. Extracts from the
      counterfeit mesh passed cytotoxicity screening tests. The FDA further recommended
      that if the mesh had been inadvertently implanted, then those patients should be
      monitored as would be the practice for any patient with an implanted surgical
      mesh.

PMID- 16404493
TI  - Cytomegalovirus-induced small-bowel hemorrhage in a patient with nonsystemic
      vasculitic neuropathy.
AB  - A 73-year-old man who was being treated with corticosteroids for nonsystemic
      vasculitic neuropathy developed small-bowel hemorrhage after ileostomy for ileus.
      Immunohistochemical staining for cytomegalovirus (CMV) antigen in the ulcer in
      the resected ileum was positive; thus, cytomegalovirus infection of the small
      intestine caused his gastrointestinal manifestations. Cytomegalovirus infection
      should be considered in the differential diagnosis of gastrointestinal diseases
      in patients with collagen vascular diseases receiving immunosuppressive agents.

PMID- 16404492
TI  - Intensity of exercise is associated with bone density change in premenopausal
      women.
AB  - INTRODUCTION: High-impact exercise is known to be beneficial for bones. However,
      the optimal amount of exercise is not known. The aim of the present study was to
      evaluate the association between the intensity of exercise and bone mineral
      density (BMD). METHODS: We performed a 12-month population-based trial with 120
      women (aged 35-40 years) randomly assigned to an exercise group or to a control
      group. The intensity of the physical activity of 64 women was assessed with an
      accelerometer-based body movement monitor. The daily activity was analyzed at
      five acceleration levels (0.3-1.0 g, 1.1-2.4 g, 2.5-3.8 g, 3.9-5.3 g, and 5.4-9.2
      g). BMD was measured at the hip, spine (L1-L4), and radius by dual-energy x-ray
      absorptiometry. The calcaneus was measured using quantitative ultrasound.
      RESULTS: Physical activity that induced acceleration levels exceeding 3.9 g
      correlated positively with the BMD change in the hip area (p<0.05-0.001). L1 BMD
      change correlated positively with activity exceeding 5.4 g (p<0.05) and calcaneal
      speed of sound with the level of 1.1-2.4 g (p< 0.05). Baseline BMD was negatively
      associated with the BMD change at the hip. CONCLUSION: The intensity of exercise,
      measured as the acceleration level of physical activity, was significantly
      correlated with BMD changes. Bone stimulation is reached during normal physical
      exercise in healthy premenopausal women. In the hip area, the threshold level for
      improving BMD is less than 100 accelerations per day at levels exceeding 3.9 g.

PMID- 16404494
TI  - Additive contribution of multiple factors in the development of pneumatosis
      intestinalis: a case report and review of the literature.
AB  - We describe a 53-year-old patient with dermatomyositis, who developed pneumatosis
      intestinalis (PI) accompanied by pneumoperitoneum, pneumoretroperitoneum,
      pneumomediastinum, and subcutaneous emphysema of the neck. The development of PI
      in our patient was possibly attributed to the effect of factors such as
      dermatomyositis, corticosteroids, methotrexate, and alpha-glucosidase inhibitor
      (AGI). The coexistence of multiple factors associated with PI might enhance the
      risk of developing PI, even though each of them alone is not sufficient to induce
      it. In particular, the use of AGIs for patients treated with immunosuppressive
      agents such as corticosteroids requires evaluation.

PMID- 16404495
TI  - Focal transient lesions of the corpus callosum in systemic lupus erythematosus.
AB  - Focal lesions limited to the splenium of the corpus callosum are rare and little
      is known about their etiology. We describe three patients with systemic lupus
      erythematosus (SLE) that presented transient lesions of the corpus callosum. We
      reviewed three patients with SLE whose magnetic resonance imaging (MRI) results
      revealed focal lesions in the splenum of corpus callosum. The medical records,
      including clinical, serological, and treatment features, were reviewed to
      determine the etiology of these lesions. Of 115 patients who had MRI for research
      purposes, three patients with focal nonhemorrhagic lesions of the corpus callosum
      were identified. All patients had active SLE at the time of MRI. One patient had
      other findings on MRI, including cerebral venous thrombosis. On follow-up MRI,
      patients had an inactive disease and the corpus callosum lesions disappeared. A
      transient lesion in the splenium of corpus callosum seems to be a nonspecific
      endpoint of different disease processes leading to vasogenic edema. The complete
      and rapid reversibility in all cases with disease control is emphasized and any
      invasive diagnostic or therapeutic approach is discouraged.

PMID- 16404496
TI  - Tuberculous peritonitis in a patient with rheumatoid arthritis treated with
      adalimumab.
AB  - We present a case of tuberculous peritonitis in a 71-year-old woman with long
      standing rheumatoid arthritis treated with adalimumab, and we review the
      association between antitumor necrosis factor therapy and tuberculosis. Our case
      illustrates that the index of suspicion of tuberculosis in these patients, even
      with atypical clinical features, must be very high, and underscores the need of
      tuberculosis screening before therapy is started.

PMID- 16404497
TI  - The practice of rheumatology in Kenya: challenges and opportunities. ILAR
      visiting professorship program report.
AB  - International League of Associations for Rheumatology (ILAR) is committed to
      promoting the care of those with musculoskeletal diseases. To further this aim,
      ILAR sponsors visiting professorships to countries with minimal or underdeveloped
      rheumatology services to promote the awareness and improve skills in the
      management of musculoskeletal conditions. Professor Luis Espinoza was sponsored
      and visited Kenya in March 2005.

PMID- 16404499
TI  - Subcutaneous panniculitis-like T-cell lymphoma misdiagnosed as lupus
      erythematosus panniculitis.
AB  - We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL),
      associated with macrophage activation syndrome, mimicking a lupus erythematosus
      panniculitis (LEP). A 29-year-old woman presented with high fever, general
      malaise, nausea, vomiting, and subcutaneous nodules and ulcerating lesions
      located on the lower extremities. The histopathology showed an infiltration of
      the panniculus, mostly involving fat, and periadnexial and perivascular
      structures consistent with lymphocytic lobular panniculitis (LLP). LLP is a
      shared feature of LEP and SPTCL. The immunophenotyping of the cell infiltrate was
      crucial for a correct diagnosis.

PMID- 16404498
TI  - Psoriatic arthritis and Klinefelter syndrome: case report.
AB  - Psoriatic arthritis (PsA) is a well-known disease characterized by psoriasis and
      inflammatory joint disease, with distinct clinical and radiological features to
      differentiate it from other arthropathies. Whereas many cases of coexistence of
      arthritis and other autoimmune disorders with chromosomal abnormalities have been
      reported, the occurrence of PsA and Klinefelter syndrome has not been reported
      previously. A case of Klinefelter syndrome and PsA was reported. This case report
      emphasizes the role played by sex hormones and chromosomal abnormalities in the
      pathogenesis of autoimmune disorder, and to our knowledge, this is an uncommon
      case of a patient with Klinefelter syndrome who developed PsA.

PMID- 16404501
TI  - Obturator internus muscle abscess mimicking septic arthritis of the hip.

PMID- 16404500
TI  - Prolactinoma and systemic lupus erythematosus: do serum prolactin levels matter?
AB  - The lactogenic hormone prolactin is produced in part by cells of the immune
      system and serves as an upregulator of immune function. Hyperprolactinemia is
      common in patients with systemic lupus erythematosus (SLE), raising the
      possibility that the hormone contributes to the excessive immune response in the
      disease. The highest levels of circulating prolactin occur in association with
      prolactin-secreting tumors, but prolactinomas have only rarely been encountered
      in patients with SLE. We present here three patients with SLE and prolactinomas.
      As with the previously reported six patients, there was no consistency in the
      presence of findings related to prolactin excess or in the coincidence of
      hyperprolactinemia with flares of SLE disease activity. We speculate that this
      may be due to genetic differences in the response to prolactin and/or to the
      presence of variant prolactin isoforms detected in the clinical immunoassay that
      have reduced or absent biologic activity.

PMID- 16404502
TI  - Unusual systemic artery to pulmonary artery malformation without evidence of
      systemic disease, trauma or surgery.
AB  - Connections between the systemic and pulmonary arterial systems are rare
      conditions that can be due to either congenital or acquired diseases such as
      anomalous systemic arterial supply to normal lung, pulmonary sequestration, and
      systemic supply to pulmonary arteriovenous malformations. Herein, a unique case
      of systemic artery to pulmonary arterial malformation and its endovascular
      treatment in a patient with no history of the usual etiologies is reported.

PMID- 16404504
TI  - Segmenting fluid effect on PCR reactions in microfluidic platforms.
AB  - This paper evaluates the compatibility of segmenting fluids for two phase flow
      applications in biomedical microdevices. The evaluated fluids are chosen due to
      the variations in fluid properties and cost, while also reflecting their use in
      the recent literature. These segmenting fluids are examined to determine their
      compatibility with the Polymerase Chain Reaction (PCR), through controlled
      experiments. The results are the first to provide a quantitative measure of
      segmenting fluid compatibility with PCR.

PMID- 16404505
TI  - Real time PCR on disposable PDMS chip with a miniaturized thermal cycler.
AB  - This paper presents the design and implementation of a low-cost miniature PCR
      device consisting of a disposable reactor chip and a miniature thermal cycler.
      The simple fabrication of the PCR chip by PDMS (Polydimethylsiloxane) does not
      need micro-machining or photolithography processes. The thermal cycler was built
      with a thin film heater for heating and a fan for rapid cooling. This device can
      perform PCR tests in a single well chip or a multiple-well chip. It can run PCR
      reactions of different volumes to meet specific application requirements. The
      smallest reaction volume tested in this work is 0.9 microL. In addition, this
      device fits any standard fluorescence microscope for real time detection, which
      makes real time PCR affordable for most research labs and clinics with a
      fluorescence microscope. Real-time PCR of E. coli stx1 has been demonstrated with
      the device described.

PMID- 16404503
TI  - Pharmacokinetic-pharmacodynamic modelling: history and perspectives.
AB  - A major goal in clinical pharmacology is the quantitative prediction of drug
      effects. The field of pharmacokinetic-pharmacodynamic (PK/PD) modelling has made
      many advances from the basic concept of the dose-response relationship to
      extended mechanism-based models. The purpose of this article is to review, from a
      historical perspective, the progression of the modelling of the concentration
      response relationship from the first classic models developed in the mid-1960s to
      some of the more sophisticated current approaches. The emphasis is on general
      models describing key PD relationships, such as: simple models relating drug dose
      or concentration in plasma to effect, biophase distribution models and in
      particular effect compartment models, models for indirect mechanism of action
      that involve primarily the modulation of endogenous factors, models for cell
      trafficking and transduction systems. We show the evolution of tolerance and time
      variant models, non- and semi-parametric models, and briefly discuss population
      PK/PD modelling, together with some example of more recent and complex
      pharmacodynamic models for control system and nonlinear HIV-1 dynamics. We also
      discuss some future possible directions for PK/PD modelling, report equations for
      general classes of novel semi-parametric models, as well as describing two new
      classes, additive or set-point, of regulatory, additive feedback models in their
      direct and indirect action variants.

PMID- 16404506
TI  - Characterization of polydimethylsiloxane (PDMS) properties for biomedical
      micro/nanosystems.
AB  - Polydimethylsiloxane (PDMS Sylgard 184, Dow Corning Corporation) pre-polymer was
      combined with increasing amounts of cross-linker (5.7, 10.0, 14.3, 21.4, and 42.9
      wt.%) and designated PDMS1, PDMS2, PDMS3, PDMS4, and PDMS5, respectively. These
      materials were processed by spin coating and subjected to common micro
      fabrication, micro-machining, and biomedical processes: chemical immersion,
      oxygen plasma treatment, sterilization, and exposure to tissue culture media. The
      PDMS formulations were analyzed by gravimetry, goniometry, tensile testing, nano
      indentation, scanning electron microscopy (SEM), Fourier transform infrared
      spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Spin coating of
      PDMS was formulation dependent with film thickness ranging from 308 microm on
      PDMS1 to 171 microm on PDMS5 at 200 revolutions per minute (rpm). Ultimate
      tensile stress (UTS) increased from 3.9 MPa (PDMS1) to 10.8 MPa (PDMS3), and then
      decreased down to 4.0 MPa (PDMS5). Autoclave sterilization (AS) increased the
      storage modulus (sigma) and UTS in all formulations, with the highest increase in
      UTS exhibited by PDMS5 (218%). PDMS surface hydrophilicity and micro-textures
      were generally unaffected when exposed to the different chemicals, except for
      micro-texture changes after immersion in potassium hydroxide and buffered
      hydrofluoric, nitric, sulfuric, and hydrofluoric acids; and minimal changes in
      contact angle after immersion in hexane, hydrochloric acid, photoresist
      developer, and toluene. Oxygen plasma treatment decreased the contact angle of
      PDMS2 from 109 degrees to 60 degrees. Exposure to tissue culture media resulted
      in increased PDMS surface element concentrations of nitrogen and oxygen.

PMID- 16404507
TI  - Flat-chip microanalytical enzyme sensor for salivary amylase activity.
AB  - It is considered that measurement of salivary alpha-amylase activity is a useful
      tool for evaluating the sympathetic nervous system. The purpose of this research
      is to demonstrate a new design of a flat-chip microanalytical enzyme sensor (flat
      chip sensor) for salivary amylase activity as a Micro-Electro-Mechanical Systems
      (MEMS), which may be used for wearable analytical systems. To meet this purpose,
      the biosensor needs to be miniaturized and to possess high-sensitivity. A pre
      column and a flat-enzyme electrode were incorporated in a flow cell of volume
      25.7 ml. In order to miniaturize the flow cell, two enzymatic membranes
      containing maltose phosphorylase obtained from Enterococcus hirae (MP membrane)
      and glucose oxidase and peroxidase (GOD-POD membrane) were immobilised on the
      same planar surface. As a result, a flat-chip sensor incorporating a flow cell as
      small as a C battery was produced. The optimum conditions of three parameters of
      the fabricated flat-chip sensor, the immobilising method of the enzymatic
      membrane, dropping volume of the mixed enzymatic solution and flow rate of the
      sample solution, were examined. An analytical system for 0-190 kU/l amylase
      activity with R(2) of 0.97 was fabricated with a sample volume of 50 microl. This
      research indicates the possibility of a wearable biosensor for continuous
      monitoring of salivary amylase activity.

PMID- 16404508
TI  - An electrokinetically-controlled immunoassay for simultaneous detection of
      multiple microbial antigens.
AB  - An electrokinetically-controlled heterogeneous immunoassay microchip for multiple
      analyte detection was developed in this study. Numerical simulation was employed
      to study the transport process in a microfluidic network (microFN). The operation
      parameters obtained from numerical simulation was then applied to immunoassay
      experiment. The effectiveness of the automatic electrokinetic control was
      demonstrated in a separate experiment using fluorescein dye. The immunoassay
      microchip was made of poly(dimethylsiloxane)(PDMS)/PDMS-coated glass using soft
      lithography and replica molding. Multi-antigen immobilization was accomplished by
      adsorbing the antigen molecules onto a PDMS-coated glass slide and by using a
      microFN. Immobilized lysate antigen of Escherichia coli O157: H7 at different
      concentrations was assayed and the lower detect limit was 3 microg/mL. The assay
      also displayed very good specificity, when different microbial lysate antigens
      were immobilized, including Escherichia coli and Helicobacter pylori, and the
      primary and secondary antibodies were mixtures of different species. The time
      required for the immunoassay, from antigen coating to signal detection, was only
      one hour. While still an un-optimized prototype, this automatic-operating, high
      throughput immunoassay microchip shows a great potential in detecting multiple
      pathogenic infections efficiently for clinical applications.

PMID- 16404509
TI  - Self-actuated, thermo-responsive hydrogel valves for lab on a chip.
AB  - An easy to fabricate, thermally-actuated, self-regulated hydrogel valve for flow
      control in pneumatically driven, microfluidic systems is described. This
      microvalve takes advantage of the properties of the hydrogel, poly(N
      isopropylacrylamide), as well as the aqueous fluid itself to realize flow
      control. The valve was designed for use in a diagnostic system fabricated with
      polycarbonate and aimed at the detection of pathogens in oral fluids at the
      location of the sample collection. The paper describes the construction and
      characterization of the hydrogel valves and their application for flow control,
      sample and reagent metering, sample distribution into multiple analysis paths,
      and the sealing of a polymerase chain reaction (PCR) reactor to suppress bubble
      formation. The hydrogel-based flow control is electronically addressable, does
      not require any moving parts, introduces minimal dead volume, is leakage and
      contaminant free, and is biocompatible.

PMID- 16404510
TI  - A SU-8/PDMS hybrid microfluidic device with integrated optical fibers for online
      monitoring of lactate.
AB  - A microfluidic device with integrated optical fibres was developed for online
      monitoring of lactate. The device consists of a SU-8 waveguide, microfluidic
      channels and grooves for the insertion of optic fibres. It was fabricated by one
      step photolithography of SU-8 polymer resist. Different channel widths (50-300
      microm) were tested in terms of detection sensitivity. A wide range of flow rates
      were applied to investigate the influence of flow rate on signal fluctuations.
      The separation between optical fibre sensor and microfluidic channel and the
      width of fluidic channel have been optimized to maximize the detection
      sensitivity. It was revealed that 250 microm of channel width is the optimum
      light path length for a compromise between detection sensitivity and interference
      of ambient light. The independence of detection signals on flow rates was
      demonstrated within the range of flow rate (0.5-5 ml/hr) tested. Compared with
      conventional lactate detection, the device is proved to have high accuracy,
      relatively low limit of detection (50 mg/L) and reasonably fast response time
      (100 sec). The fabrication of device is simple and low cost. The present work has
      provided some fundamental data for further system optimization to meet specific
      detection requirements.

PMID- 16404511
TI  - Ultrafast nanolaser flow device for detecting cancer in single cells.
AB  - Currently, pathologists rely on labor-intensive microscopic examination of tumor
      cells using staining techniques originally devised in the 1880s that depend
      heavily on specimen preparation and that can give false readings. Emerging
      BioMicroNanotechnologies (Gourley, 2005) have the potential to provide accurate,
      realtime, high throughput screening of tumor cells without invasive chemical
      reagents. These techniques are critical to advancing early detection, diagnosis,
      and treatment of disease. Using a new technique to rapidly assess the properties
      of cells flown through a nanolaser semiconductor device, we discovered a method
      to rapidly assess the respiratory health of a single mammalian cell. The key
      discovery was the elucidation of biophotonic differences in normal and
      transformed (cancer) mouse liver cells by using intracellular mitochondria as
      biomarkers for disease. This technique holds promise for detecting cancer at a
      very early stage and could nearly eliminate delays in diagnosis and treatment.

PMID- 16404512
TI  - Self-assembled three dimensional radio frequency (RF) shielded containers for
      cell encapsulation.
AB  - This paper describes the construction of three dimensional (3D) encapsulation
      devices in large numbers, using a novel self-assembling strategy characterized by
      high mechanical stability, controlled porosity, extreme miniaturization, high
      reproducibility and the possibility of integrating sensing and actuating
      electromechanical modules. We demonstrated encapsulation of microbeads and cells
      within the containers, thereby demonstrating one possible application in cell
      encapsulation therapy. Magnetic resonance (MR) images of the containers in
      fluidic media suggest radio frequency (RF) shielding and a susceptibility effect,
      providing characteristic hypointensity within the container, thereby allowing the
      containers to be easily detected. This demonstration is the first step toward the
      design of 3D, micropatterned, non-invasively trackable, encapsulation devices.

PMID- 16404513
TI  - Development of blood extraction system for health monitoring system.
AB  - We focus on research to develop a compact human blood sampling device used for
      the Self Monitoring of Blood Glucose (SMBG). The SMBG comprises: (1) an
      indentation system using a shape memory alloy (SMA) actuator to force a
      microneedle through the skin; (2) a micro electrical pumping system to extract
      blood using a bimorph type piezoelectric microactuator; (3) a biosensor using an
      enzyme such as glucose oxidase (GOx) to detect and evaluate the amount of glucose
      in extracted blood. A titanium microneedle the same size as a female mosquito's
      labium (60 mum outer diameter, 25 mum inner diameter) was produced by the sputter
      deposition method. The mechanical design of the device was based upon the
      mosquito's blood sampling mechanism. The blood extraction system worked well. We
      measured the performance of the principal components: the indentation load for a
      microneedle of external diameter 100 mum was found to be 0.1 N. The pumping
      system has an extraction speed of about 2 mul/min for whole blood. This is
      similar to that achieved by the mosquito.

PMID- 16404514
TI  - Early intestinal changes following abdominal radiotherapy comparison of
      endpoints.
AB  - PURPOSE: To compare tests for intestinal function with clinical scores after
      abdominal irradiation. PATIENTS AND METHODS: At the Department of Radiotherapy,
      Erfurt, Germany, intestinal changes were studied in 91 patients receiving
      abdominal radiotherapy between 1992 and 1996. Conventional fractionation (1.8-2
      Gy per fraction, total doses 30.6-62.5 Gy) was applied. Before and at weekly
      intervals during radiotherapy, the clinical response was scored according to
      RTOG/EORTC for the upper and lower gastrointestinal (GI) tract. Resorption tests
      for vitamin B(12) and D-xylose were performed before the onset and immediately
      after treatment. RESULTS: The clinical response displayed a well-defined dose
      effect relationship with grade 1 effects in 5% and 50% of the patients at about
      10 Gy and 50 Gy, respectively. For grade 2 reactions, 5%- and 50%-effective doses
      were 20-30 Gy and 60-80 Gy. Effects in the upper and lower GI tract were highly
      correlated. Changes in body weight did not show a correlation with other clinical
      symptoms. Changes in resorption also displayed a significant dose effect.
      However, no correlation was found with the clinical symptoms in the individual
      patient. CONCLUSION: In the present study, the clinical manifestation of
      intestinal side effects according to RTOG/EORTC criteria was reflected by neither
      the vitamin B(12) nor by the D-xylose resorption test. Hence, these tests cannot
      be regarded as useful for objective quantitation of intestinal radiation injury.

PMID- 16404515
TI  - High-dose intracoronary irradiation after de novo stent implantation results of
      the EVEREST (Evaluation of Endoluminal Radiation in Elective Stenting) trial.
AB  - PURPOSE: This randomized study was designed to compare the efficacy of high-dose
      coronary beta-radiation after intravascular ultrasound-(IVUS-)guided direct
      stenting with sham treatment in patients with de novo lesions. PATIENTS AND
      METHODS: 32 patients were enrolled in the study protocol. Following angioplasty
      procedure, intracoronary brachytherapy was performed with the Novoste Beta-Cath
      System. The prescribed dose was 24 Gy referred to the lamina elastica externa.
      Quantitative coronary angiography and IVUS were performed to analyze the treated
      coronary vessel. RESULTS: Angiographic results revealed a significantly smaller
      minimal lumen diameter compared with the pos-tprocedural minimal lumen diameter
      within the stented segment (p = 0.004) in the nonirradiated group. The same
      significant result was observed in the injured segment of the nonirradiated
      patients (p = 0.011). The IVUS data revealed a significant increase of the plaque
      volume after 8 months in the nonirradiated group compared to the post-procedural
      value (irradiated 5.41 +/- 8.83 mm(3) vs. nonirradiated 21.11 +/- 16.08 mm(3); p
      = 0.001). Late luminal loss was significantly greater in the nonirradiated group
      (p = 0.004). The primary clinical endpoint (death, myocardial infarction, repeat
      target lesion revascularization, percutaneous revascularization, coronary artery
      bypass surgery) was reached by seven irradiated (33.3%) and four (18.2%)
      nonirradiated patients (p = 0.623). Late stent thrombosis was observed in one
      irradiated patient. CONCLUSION: The EVEREST trial has demonstrated the
      feasibility of high-dose intracoronary brachytherapy in de novo coronary lesions.
      There is a significant reduction of neointimal proliferation within the stented
      segment. Nevertheless, this benefit is vitiated by an increase of restenotic
      lesions outside the stent segment.

PMID- 16404516
TI  - Reoxygenation of human coronary smooth muscle cells suppresses HIF-1alpha gene
      expression and augments radiation-induced growth delay and apoptosis.
AB  - BACKGROUND AND PURPOSE: Catheter-based coronary brachytherapy with beta- and
      gamma-radiation is an evidence-based method to prevent restenosis after
      percutaneous transluminal coronary angioplasty (PTCA) and stent implantation, but
      the outcome may be subject to improvements. Physiological studies suggest that
      most of the target cells of brachytherapy in coronary arteries after PTCA are
      hypoxic. A lack of oxygen decreases the effect of low LET (linear energy
      transfer) irradiation. The authors assumed that reoxygenation of hypoxic human
      coronary smooth muscle cells (HCSMCs) improves the results of coronary
      brachytherapy. The expression of hypoxia-inducible factor 1alpha (HIF-1alpha)
      gene, and the rates of growth and apoptosis of hypoxic and reoxygenated HCSMCs
      after gamma-irradiation were therefore analyzed. MATERIAL AND METHODS: An in
      vitro model of megacolonies of HCSMCs was developed. After exposure to chronic
      hypoxia the HCSMCs were irradiated with graded doses of 2, 4, 8, and 16 Gy using
      a (60)Co source either under hypoxia (pO(2) < 3 mmHg) or after reoxygenation
      (pO(2) approximately 150 mmHg). RT-PCR (reverse transcription-polymerase chain
      reaction) analysis was used to quantify HIF-1alpha gene expression and the growth
      of HCSMC megacolonies was measured serially. The oxygen enhancement ratio (OER)
      was calculated from the specific growth delay. Apoptosis of HCSMCs was quantified
      by counting cells with specific DNA strand breaks using the TUNEL assay. RESULTS:
      HIF-1alpha gene expression was markedly suppressed in reoxygenated cells versus
      hypoxic cells 30 min after gamma-irradiation at all radiation doses (158 +/- 46%
      vs. 1,675 +/- 1,211%; p < 0.01). Apoptosis was markedly increased in reoxygenated
      HCSMCs. The OER was 1.8 (95% CI [confidence interval] 1.3-2.4). Therefore,
      reoxygenated HCSMCs require 44% less radiation dose to achieve the equivalent
      biological radiation effect compared to hypoxic HCSMCs. CONCLUSION: Reoxygenation
      of coronary smooth muscle cells should be considered an option to increase
      efficacy of coronary brachytherapy. This could be used to reduce radiation dose
      and associated late side effects.

PMID- 16404518
TI  - Increased radioiodine uptake of thyroid cell cultures after external irradiation.
AB  - BACKGROUND: Radioiodine uptake (RIU) is one of the main prognostic factors for
      curative results of radioiodine therapy in patients with differentiated thyroid
      cancer. Some days after application of (131)I, the uptake of a subsequent
      administration of radioiodine was found to be reduced. In contrast, early after
      irradiation with high-energy photons glucose and amino acid uptake were observed
      to be increased. Effects of external irradiation on RIU of thyrocytes using high
      energy photons have not been investigated so far. MATERIAL AND METHODS: Two
      different cell lines (FRTL-5 and ML-1 cells) derived from thyroid tissue were
      studied in vitro. Cell lines were either incubated with (131)I only (controls) or
      additionally irradiated with single doses of 6 or 10 Gy of high-energy photons
      using a linear accelerator. Cell number and RIU were determined 24-96 h after
      (131)I application. RIU measurements were repeated after application of sodium
      perchlorate in excess to investigate specificity of the uptake. Statistical
      analyses were performed using non-parametric tests. RESULTS: Incubation with
      radioiodine as well as irradiation with high-energy photons slowed down
      proliferation in investigated cell lines significantly. Irradiation with solely
      (131)I resulted in stable or slightly decreased iodide uptake. Compared to those
      cells, the RIU increased significantly in externally irradiated cells, i. e.,
      additional irradiation with 10 Gy resulted in an almost threefold increase of RIU
      in FRTL-5 after 72 h. The increase of RIU after irradiation was dose-dependent in
      both cell lines and could be blocked by perchlorate excess. CONCLUSION: It could
      be demonstrated that external irradiation increases RIU in thyroid cell cultures
      early after irradiation. The increase was dose-dependent and specific, as it
      could be blocked by perchlorate. This effect appears to be similar to the
      increase of other actively transported substances after irradiation with high
      energy photons. Therefore, the results of this study may contribute to the
      knowledge of a generalized irradiation-induced mechanism which causes the
      activation of different cellular transporters. The clinical impact of these
      findings on combined therapy concepts has to be investigated in further
      experiments.

PMID- 16404517
TI  - Neoadjuvant interstitial high-dose-rate (HDR) brachytherapy combined with
      systemic chemotherapy in patients with breast cancer.
AB  - BACKGROUND AND PURPOSE: This is the first study investigating neoadjuvant
      interstitial high-dose-rate (HDR) brachytherapy combined with chemotherapy in
      patients with breast cancer. The goal was to evaluate the type of surgical
      treatment, histopathologic response, side effects, local control, and survival.
      PATIENTS AND METHODS: 53 patients, who could not be treated with breast
      conserving surgery due to initial tumor size (36/53) or due to an unfavorable
      breast-tumor ratio (17/53), were analyzed retrospectively. All but one were in an
      intermediate/high-risk group (St. Gallen criteria). The patients received a
      neoadjuvant protocol consisting of systemic chemotherapy combined with
      fractionated HDR brachytherapy (2 x 5 Gy/day, total dose 30 Gy). In cases, where
      breast-conserving surgery was performed, patients received additional external
      beam radiotherapy (EBRT, 1.8 Gy/day, total dose 50.4 Gy). In patients, who
      underwent mastectomy but showed an initial tumor size of T3/T4 and/or more than
      three infiltrated lymph nodes, EBRT was also performed. RESULTS: In 30/53
      patients (56.6%) breast-conserving surgery could be performed. The overall
      histopathologic response rate was 96.2% with a complete remission in 28.3% of
      patients. 49/53 patients were evaluable for follow-up. After a median of 58
      months (45-72 months), one patient showed a mild fibrosis of the breast tissue,
      three patients had mild to moderate lymphatic edema of the arm. 6/49 (12.2%)
      patients died of distant metastases, 4/49 (8.2%) were alive with disease, and
      39/49 (79.6%) were free from disease. Local recurrence was observed in only one
      case (2%) 40 months after primary therapy. After mastectomy, this patient is
      currently free from disease. CONCLUSION: The combination of interstitial HDR
      brachytherapy and chemotherapy is a well-tolerated and effective neoadjuvant
      treatment in patients with breast cancer. Compared to EBRT, treatment time is
      short. Postoperative EBRT of the whole breast -- if necessary -- is still
      possible after neoadjuvant brachytherapy. Even though the number of patients does
      not permit definite conclusions, the results are promising regarding survival and
      the very low rate of local recurrences.

PMID- 16404519
TI  - Portal verification of high-energy electron beams using their photon
      contamination by film-cassette systems.
AB  - BACKGROUND AND PURPOSE: Though electron beams are widely used in radiotherapy,
      their verification is not well established in clinical practice. The present
      study compares the suitability of several sensitive film-cassette systems for
      electron-portal verification by contaminating photons. MATERIAL AND METHODS: The
      characteristics of the optical density curves of film-cassette combinations were
      determined by exposing them to the bremsstrahlung contamination of a variety of
      electron beams. Using a Las-Vegas Phantom the spatial low-contrast resolution of
      the combinations was investigated. The absorbed dose rates due to the contaminant
      photons were measured for different geometric conditions. RESULTS: Suitable film
      cassette combinations were found for portal verification of all usual electron
      energies. The best image quality was obtained using the EC film and the EC-L
      cassettes. For electron energies higher than 6 MeV some film-cassette
      combinations are suitable to verify abutted electron and photon portals using the
      same film sheet. CONCLUSION: The verification of electron portals and of abutted
      electron-photon portals can be performed by sensitive film-cassette systems with
      an image quality comparable to photon-beam verification.

PMID- 16404520
TI  - Uterus necrosis after radiochemotherapy in two patients with advanced cervical
      cancer.
AB  - BACKGROUND: Simultaneous platinum-based radiochemotherapy is the standard of care
      for patients with advanced or node-positive cancer of the uterine cervix. A large
      body of literature concerning therapy-related acute and late morbidity is
      available. Chemoradiation-associated necrosis of the uterus has not been
      described so far. CASE REPORT: Two patients are reported who were treated by
      combined chemoradiation between 2004 and 2005 for histologically confirmed
      cervical cancer following laparoscopic staging. Both patients were diagnosed with
      squamous cell cancer of the cervix FIGO stage IIB (T2b pN1 pM1 LYM G2) and FIGO
      IIIA (T3a pN1 M0 G2), respectively. External-beam radiotherapy was applied in a 3
      D-planned four-field technique, covering pelvic lymph nodes and primary tumor.
      Patient #1 received additional paraaortic irradiation. Patient #2 underwent 5 x 5
      Gy brachytherapy covering the tumor. Simultaneously, cisplatin was given to both
      patients. Following chemoradiation, both patients developed pelvic pain and an
      elevation of C-reactive protein (CRP) in the presence of a normal leukocyte
      count. Both patients underwent relaparoscopy, and necrosis of the uterus combined
      with partial necrosis of the bladder was diagnosed in patient #1. Patient #1
      underwent total supralevatoric exenteration and patient #2 laparoscopically
      assisted hysterectomy with bilateral salpingo-oophorectomy. CONCLUSION: In
      patients with persisting or incident pelvic pain, questionable findings in
      imaging techniques and/or elevated inflammation parameters following completion
      of chemoradiation for cervical cancer, differential diagnosis should include
      radiogenic necrosis of the uterus and other pelvic organs. Laparoscopy is an
      ideal technique to exclude or confirm this diagnosis.

PMID- 16404521
TI  - Fluorophore(s) appended fullerene dyads and triads for probing photoinduced
      energy transfer: syntheses, electronic structure, and fluorescence studies.
AB  - Fullerene, C(60) was functionalized to possess one or two fluorophore entities.
      The fluorophore-fullerene dyads thus synthesized contain either a naphthalene,
      pyrene, or fluorene entity while the triads contain either a pyrene or fluorene
      entity in addition to a naphthalene entity. The redox behavior of these dyads and
      triads were probed by cyclic voltammetric technique, while the geometry and
      electronic structures were deduced from ab initio B3LYP/3-21G(*) method. Steady
      state emission studies revealed the occurrence of energy transfer from the
      singlet excited fluorophore to the fullerene entity in the case of the dyads
      while the occurrence of step-by-step sequential energy transfer is envisioned in
      the case of the triads. A better 'antenna-effect' owing to the extended range of
      excitation wavelength to induce energy transfer to the appended fullerene has
      been achieved in the case of the triads.

PMID- 16404523
TI  - Amino acids on the rampant primordial Earth: electric discharges and the hot
      salty ocean.
AB  - For more than 50 years scientists who study prebiotic chemistry have been dealing
      with chemical evolution as it could have possibly taken place on the primordial
      Earth. Since we will never know what processes have really taken place around 3.8
      to 4 billion years ago we can only come up with plausible reaction pathways that
      work well in an early Earth scenario as indicated by geochemists. In our work we
      have investigated the plausibility of one particularly important branch of
      prebiotic chemistry, the formation of amino acids, by electric discharge in a
      neutral atmosphere composed of carbon dioxide, nitrogen, and water vapour above
      liquid water. We have found yields of various amino acids under different
      temperature conditions, with and without sodium chloride in a simulated
      primordial lake or ocean within extremely short reaction times compared to the
      timespan available for prebiotic evolution.

PMID- 16404524
TI  - Hinge peptide combinatorial libraries for inhilbitors of botulinum neurotoxins
      and saxitoxin: deconvolution strategy.
AB  - Abstract Combinatorial library screening offers a rapid process for identifying
      potential therapies to toxins. Hinge peptide libraries, which rely on
      conformational diversity rather than traditional molecular diversity, reduce the
      need for huge numbers of syntheses and screening steps and greatly expedite the
      discovery process of active molecules. Hinge peptide libraries having the
      structures: Acetyl-X1-X2-hinge-X3-X4-NH2 (capped) and X1-hinge-X2-X3 (uncapped),
      where X1 through X4 are near-equimolar mixtures of twelve L-amino acids and hinge
      = 4-aminobutyric acid, were screened for inhibitory activity in bioassays for
      botulinum neurotoxins A and B (BoNT/A, BoNT/B) and saxitoxin. The zinc protease
      activity of the reduced light chains of BoNT/A and /B was assayed by measuring
      the cleavage of synthetic substrates. Saxitoxin activity was measured by the
      restoration of the viability of neuroblastoma cells treated with ouabain and
      veratridine. Deconvolution of libraries was accomplished by fixing one position
      at a time beginning with the C-terminus. Primary library subsets in which
      position 4 was fixed showed moderate levels of inhibition for BoNT/A. Secondary
      library subsets showed stronger inhibition in the bioassays. In each of the
      bioassays, inhibitory potency was stronger when the second position to be fixed
      was on the opposite side of the hinge, rather than on the same side with respect
      to the C-terminus, suggesting that the hinge facilitates the interaction of side
      chains. Inhibitors for all three of the toxins studied were discovered within
      library subsets, although not necessarily in primary subsets. These studies
      demonstrate that (1) the best strategy for deconvoluting hinge peptide libraries
      is by fixing residues alternately on each side of the hinge moiety, and (2) it is
      essential to investigate secondary subsets even when primary subsets are
      inactive. The present findings support the concept that the increased flexibility
      imposed by the inclusion of a central hinge residue in small peptides increases
      the opportunity for side chain interactions, providing a distinct advantage for
      hinge peptide libraries over conventional peptide libraries. Hinge peptide
      libraries are a rich source of novel ligands for modulation of biomechanisms. The
      library subsets uncovered in this study may possess peptides that will lead to
      effective therapies to neurotoxin poisoning.

PMID- 16404525
TI  - Efficient library synthesis of imidazoles using a multicomponent reaction and
      microwave irradiation.
AB  - Optimization of Radziszewski's four-component reaction employing a microwave
      assisted protocol, led to a small library of 48 imidazoles with a success rate of
      65% (conversion > 45%). All three diversity points of the four-component reaction
      were varied. Aromatic and aliphatic inputs were successfully implemented and mono
      , di-, tri- and tetrasubstituted imidazoles with various substitution patterns
      were synthesized. Furthermore, unsymmetrical diketones could successfully be used
      which improved the intrinsic diversity of the method significantly. If the
      unsymmetrical diketone 1,2-phenylpropanedione (R1 and R2) was used two
      regioisomers were formed. Depending on the type of amine (R4) and aldehyde (R3)
      applied, regioselectivity was modest to good. Based on these results, a reaction
      mechanism is proposed.

PMID- 16404526
TI  - Three-component reaction between triphenylphosphine, dialkyl
      acetylenedicarboxylates and urea or N-methylurea.
AB  - The stabilized phosphoranes, obtained from the three-component reaction between
      dialkyl acetylenedicarboxylates and urea or N-methylurea in the presence of
      triphenylphosphine, undergo a smooth reaction in boiling toluene to produce
      iminophosphoranes in good yields. Under the same reaction conditions, the
      phosphorane obtained from N-methylurea and dimethyl acetylenedicarboxylate yields
      methyl 1-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylate.

PMID- 16404527
TI  - An efficient synthesis of new C-2 aryl substituted quinolines based on three
      component imino Diels-Alder reaction.
AB  - New effective approach to the synthesis of a wide variety of C-2 nitro or
      aminophenyl substituted quinolines was reported using diverse intermediate 4-(2
      oxopyrrolinidyl-1)-tetrahydroquinolines that were prepared by a three component
      imino Diels-Alder reaction was reported. The key aromatisation process occurs
      cleanly with the loss of the 2-oxopyrrolinidyl-1 fragment.

PMID- 16404529
TI  - Similarity study of serine proteases inhibitors.
AB  - Two-dimensional structural similarity calculations have been applied to estimate
      binding affinities of serine proteases inhibitors. 1103 trypsin binders, 1268
      thrombin binders and 714 fXa binders have been used to compare experimental and
      predicted data. The predictions generally provide reasonable estimates of the
      observed binding affinities. The accuracy of the predictions depends on the size
      of the dataset, but not dramatically. The accuracy also depends on the number of
      similar structures used to make the calculations, with a number from 3 to 6
      usually being optimal. The binding affinity is noticeably more sensitive to the
      inhibitor structure in the case of fXa relative to thrombin.

PMID- 16404528
TI  - Molecular similarity and diversity in chemoinformatics: from theory to
      applications.
AB  - This review is dedicated to a survey on molecular similarity and diversity. Key
      findings reported in recent investigations are selectively highlighted and
      summarized. Even if this overview is mainly centered in chemoinformatics,
      applications in other areas (pharmaceutical and medical chemistry, combinatorial
      chemistry, chemical databases management, etc.) are also introduced. The
      approaches used to define and describe the concepts of molecular similarity and
      diversity in the context of chemoinformatics are discussed in the first part of
      this review. We introduce, in the second and third parts, the descriptions and
      analyses of different methods and techniques. Finally, current applications and
      problems are enumerated and discussed in the last part.

PMID- 16404531
TI  - Relationships among epipelic diatom taxa, bacterial abundances and water quality
      in a highly polluted stream catchment, bursa -- Turkey.
AB  - Nilufer Stream is an important water source in the industrial and metropolitan
      city of Bursa, Turkey. The stream catchment has been influenced by high human
      impact. The downstream receives sewage water from households and industry,
      whereas the headwater of the stream has a source of high-quality drinkable water.
      In this paper, abundances of epipelic diatom taxa, faecal coliforms (FC), total
      coliforms (TC) and total bacteria (TB) were studied in relation to measured
      environmental variables (T, pH, DO, BOD(5), EC, TDS) for the period July 1997 to
      June 1998 at six stations in the heavily polluted Nilufer Stream catchment. It is
      observed that the physicochemical variables and bacterial abundances varied
      seasonally at all stations, and the level of pollution reached at its highest
      point in the summer. The results of Kruskal-Wallis and one-way ANOVA indicated
      that DO gradually decreased, whereas BOD(5), EC, TDS, TB, FC and TC gradually
      increased from upstream to downstream. The ordination method of Principal
      Component Analysis (PCA) was carried out for both biologic and physicochemical
      variables, and the results were supported by the former statistical procedures.
      The frequency of occurrence of dominant diatoms was examined in relation to the
      spatial variations in chemical constituents. Both diatoms and bacteria showed
      strong correlations with the measured physicochemical variables. In Canonical
      Correlation Analysis (CANCORR) measures of bacterial abundances also displayed
      strong correlations with abundances of 11 diatom taxa. The results showed that
      the stream catchment is polluted gradually from upstream to downstream. In
      addition, pollution load in the stream catchment has been gradually increased,
      compared with recent years. Urbanisation and industrialisation of the city have
      affected increasing pollution in Nilufer Stream. The results also indicated that
      diatoms are not affected by environmental variables such as bacteria. Bacteria
      are more sensitive to organic pollution, while diatoms are indicators of
      different environmental conditions.

PMID- 16404532
TI  - PCB levels and trends within the Detroit River-Western Lake Erie basin: a
      historical perspective of ecosystem monitoring.
AB  - An international workshop held in the spring of 2002 convened a group of
      technical experts to address monitoring, modeling, and management of PCBs within
      the Detroit River-Western Lake Erie basin. Participants shared and discussed a
      diverse set of research data bases pertaining to PCB levels within the region,
      discussed observed changes within different components of the local ecosystem,
      and identified several primary issues impacting future PCB management strategies.
      Results presented at the workshop indicate dramatic reductions in PCB
      contamination levels have been observed in much of study area between the late
      1970s and mid-1990s. Estimates of loadings attributable to water and atmospheric
      sources have generally declined, as have PCB concentrations in herring gull eggs,
      smelt and walleye. Nevertheless, additional improvements have not been observed
      during recent years and elevated contamination levels remain a concern within
      local hot spots, particularly in the lower Detroit River and Trenton Channel. A
      primary recommendation broadly supported by workshop participants is the need to
      maintain, support, and coordinate a comprehensive ecosystem monitoring program
      for the Detroit River-Western Lake Erie basin, one that incorporates both near
      field and far-field monitoring elements. Such a program is crucial to provide
      necessary data in support of understanding ecosystem trends, calculating annual
      mass loadings to the system, assessing impacts of remediation actions, developing
      improved modeling frameworks, and formulating cost-effective management
      strategies for the future.

PMID- 16404534
TI  - Spatio-temporal fluxes in particulate organic carbon in a tropical coastal
      lagoon.
AB  - Temporal and spatial variations in particulate organic carbon (POC) in relation
      to primary production, chlorophyll a, phaeophytin, plankton abundance, secondary
      production and suspended particulate matter (SPM) were studied monthly for 1 year
      from April 1996 to March 1997 in a shallow tropical coastal lagoon on the
      southwest coast of India. Though temporal variations in all components were
      significant, spatial variabilities were not statistically significant. POC values
      range from 200 to 5690 mg C m(3) h(-1), while primary production, chlorophyll a,
      and phaeophytin varied between 0.02 and 14.53 mg C m(-3) h(-1), 0.87 and 23.11 mg
      m(-3) and 3.02 and 30.581 mg m(-3), respectively. Phytoplankton and zooplankton
      abundance varied from 0.01 to 655.5 x 10(5) no m(-3) and negligible to 7.08 x
      10(5) no m(-3) respectively; secondary production from 10 to 490 mg C m(-3) and
      SPM between 0.38 and 74.43 x 10(4) mg m(-3) during this study. Temporally,
      postmonsoon months were observed to have the highest concentrations of POC in the
      lagoon waters. The bulk of the POC pool in the lagoon was composed of secondary
      producers (72%), followed by chlorophyll a (21%), phaeophytin (7%) and suspended
      particulate matter of inorganic origin (< 0.1%).

PMID- 16404533
TI  - Element levels in snakes in South Carolina: differences between a control site
      and exposed site on the Savannah River site.
AB  - Levels of 18 elements, including lead, mercury, selenium, and uranium, were
      examined in three species of snakes from an exposed and reference site on the
      Department of Energy's Savannah River Site in South Carolina. We tested the
      hypotheses that there were no differences as a function of species, and there
      were no difference between the exposed and control site for blood and muscle
      (tail) samples for banded water snake (Nerodia fasciata), brown water snake (N.
      taxispilota) and cotton mouth (Akistrodon piscivorous). The banded water snakes
      collected were significantly smaller than the other two species. For blood, there
      were significant species differences only for barium, copper, selenium, uranium
      and zinc, while for muscle tissue there were significant interspecific
      differences in aluminum, arsenic, barium, cobalt, cesium, copper, iron, lead,
      mercury, manganese, strontium, vanadium and zinc, suggesting that muscle tissue
      in the tail is a better indicator of potential interspecific differences. It is
      also easier logistically to collect tail tissue than blood. Where one species had
      significantly higher levels than the other species in muscle tissue levels,
      cottonmouth had higher levels of five elements (aluminum, cobalt, lead, mercury,
      vanadium), brown water snake had two (lead, strontium), and banded water snake
      had only barium. There were few significant differences between the control and
      reference site for levels of blood, but several for muscle tissue. All three
      species had significantly higher levels of arsenic and manganese at Tim's Branch
      than the reference site, and nickel and uranium were significantly higher for
      banded water snake and cotton mouth, the larger species. Individuals with high
      exposure of one element were exposed to high levels of other elements.

PMID- 16404535
TI  - Changes of land use and of ecosystem service values in Sanjiang Plain, Northeast
      China.
AB  - Agricultural activities, especially reclamation, are considered major threats to
      the wetland ecosystems in Sanjiang Plain, the largest concentrated area of the
      freshwater wetlands in China. In the past decades, the area of the cultivated
      land and its grain production have been increased at the cost of wetlands
      shrinkage. The large-scale land reclamation severely affected the ecosystems in
      this region. However, such effects at the regional scale are seldom evaluated
      quantitatively. We used three datasets of LANDSAT MSS and/or TM imagery to
      estimate the area changes and the transition of land use types from 1980 to 2000.
      We also valued changes in ecosystem services delivered by each land category
      using value coefficients published by Costanza et al. Sensitivity analysis
      suggested that these estimates were relatively robust. Finally, the contribution
      of various ecosystem functions was ranked to the overall value of the ecosystem
      services in this study. According to our estimates, the total annual ecosystem
      service values in Sanjiang Plain have declined by about 40% between 1980 and 2000
      (156284-182572.18 million US dollars in total over 20 years). This substantial
      decline is largely attributed to the 53.4% loss of wetlands. For individual
      ecosystem functions, waste treatment, water supply and disturbance regulation
      account for more than 60% to the total ecological values. During those two
      decades, the contribution of disturbance regulation, cultural and recreation
      decreased, while the contribution of water regulation, nutrient cycling, food
      production, raw materials and climate regulation increased during the same
      period. We also put forward a few proposals concerning the future land use policy
      formulation and sustainable ecosystems. They are adjusting the 'food first'
      agricultural policy, establishing more nature reserves for wetlands, creating
      systems for the rational use of water, harnessing the degraded cultivated land
      and encouraging eco-tourism.

PMID- 16404536
TI  - Combining logistic models with multivariate methods for the rapid biological
      assessment of rivers using macroinvertebrates.
AB  - This work represents an attempt to define a simple method to classify the
      relative degree of disturbance of sites in lotic systems on the basis of
      comparison of their faunistic composition with reference sites. Two ecotypes were
      selected in northern Portugal where benthic invertebrates were sampled in reaches
      with different levels of contamination. As a first stage, previous Geographic
      Information System information was used to define reference sites in each
      ecotype. Afterwards, multivariate techniques and non linear estimation models
      were combined to assess biological quality. This method allowed us to quantify
      sites according to increasing levels of contamination, after the probabilities of
      occurrence of taxa along a gradient of contamination taking into account the
      reference condition. The results suggest that this method is sensitive to organic
      pollution, easy to interpret, namely the species tolerance, and could be a good
      framework to establish regional rankings depending on the ecological impact of
      river sites.

PMID- 16404537
TI  - Extreme spatial variability and unprecedented methylmercury concentrations within
      a constructed wetland.
AB  - We began monitoring concentrations of both total mercury (THg) and methylmercury
      (MeHg) in surface water at Stormwater Treatment Area-2 (STA) on July 20, 2000.
      This 2602 hectare STA was constructed with three independent marshes to remove
      phosphorus from agricultural runoff and reduce eutrophication in the northern
      Everglades. However, there was concern that in doing so, STA-2 might
      inadvertently worsen the existing mercury problem in the Everglades. Accordingly,
      operating permits stipulated that flow-through operation of these treatment cells
      could not begin until concentrations of THg and MeHg in the interior marsh were
      not significantly greater than corresponding concentrations in the supply canal.
      Cells 2 and 3 quickly met the start-up criteria in the fall of 2000. In contrast,
      Cell 1 exhibited anomalously high MeHg concentrations in the fall of 2000 and
      2001, and the summer of 2002. During the last such event, water-column
      concentrations in Cell 1 reached 32 ng THg/L and an unprecedented 20 ng MeHg/L.
      Tissue Hg in resident fishes reached levels as high as 430 ng/g in mosquitofish,
      Gambusia holbrooki, 930 ng/g in sunfish, Lepomis spp., and 2000 ng/g in
      largemouth bass, Micropterus salmoides. Guided by results from the monitoring
      program, flow rate and water depth were managed as a means to alter sulfur
      biogeochemistry and, thereby, reduce in situ mercury methylation. This adaptive
      management strategy likely played a role in the decline in water-column
      concentrations of THg and MeHg in Cell 1 by late 2002 and the subsequent declines
      in tissue Hg levels in resident fishes. Cell 1 finally met formal start-up
      criteria on November 26, 2002.

PMID- 16404538
TI  - A water quality monitoring network design methodology for the selection of
      critical sampling points: Part I.
AB  - The principal instrument to temporally and spatially manage water resources is a
      water quality monitoring network. However, to date in most cases, there is a
      clear absence of a concise strategy or methodology for designing monitoring
      networks, especially when deciding upon the placement of sampling stations. Since
      water quality monitoring networks can be quite costly, it is very important to
      properly design the monitoring network so that maximum information extraction can
      be accomplished, which in turn is vital when informing decision-makers. This
      paper presents the development of a methodology for identifying the critical
      sampling locations within a watershed. Hence, it embodies the spatial component
      in the design of a water quality monitoring network by designating the critical
      stream locations that should ideally be sampled. For illustration purposes, the
      methodology focuses on a single contaminant, namely total phosphorus, and is
      applicable to small, upland, predominantly agricultural-forested watersheds. It
      takes a number of hydrologic, topographic, soils, vegetative, and land use
      factors into account. In addition, it includes an economic as well as logistical
      component in order to approximate the number of sampling points required for a
      given budget and to only consider the logistically accessible stream reaches in
      the analysis, respectively. The methodology utilizes a geographic information
      system (GIS), hydrologic simulation model, and fuzzy logic.

PMID- 16404539
TI  - Benthic impacts of intertidal oyster culture, with consideration of taxonomic
      sufficiency.
AB  - An investigation of the impacts from elevated intertidal Pacific oyster culture
      in a New Zealand estuary showed enhanced sedimentation beneath culture racks
      compared with other sites. Seabed elevation beneath racks was generally lower
      than between them, suggesting that topographic patterns more likely result from a
      local effect of rack structures on hydrodynamic processes than from enhanced
      deposition. Compared with control sites, seabed sediments within the farm had a
      greater silt/clay and organic content, and a lower redox potential and shear
      strength. While a marked trend in macrofaunal species richness was not evident,
      species composition and dominance patterns were consistent with a disturbance
      gradient, with farm effects not evident 35 m from the perimeter of the racks. Of
      the environmental variables measured, sediment shear strength was most closely
      associated with the distribution and density of macrofauna, suggesting that human
      induced disturbance from farming operations may have contributed to the
      biological patterns. To evaluate the taxonomic sufficiency needed to document
      impacts, aggregation to the family level based on Linnean classification was
      compared with an aggregation scheme based on ;general groups' identifiable with
      limited taxonomic expertise. Compared with species-level analyses, spatial
      patterns of impact were equally discernible at both aggregation levels used,
      provided density rather than presence/absence data were used. Once baseline
      conditions are established and the efficacy of taxonomic aggregation
      demonstrated, a ;general group' scheme provides an appropriate and increasingly
      relevant tool for routine monitoring.

PMID- 16404540
TI  - Interactions of atmospheric deposition with coniferous canopies in Estonia.
AB  - Throughfall and open field bulk precipitation were measured at three coniferous
      sites during 1995-2002 in the framework of ICP Integrated Monitoring and at five
      coniferous sites during 1996-2002 in the framework of ICP Forests (Level II). The
      coniferous canopies acted as a sink for nitrate and ammonium and as a source for
      base cations: Ca(2+), Mg(2+) and K(+). The estimated share of SO(4)-S dry
      deposition from total deposition was 1.5-4 times higher for dormant period
      compared to growing period. During the study period average annual throughfall
      and bulk deposition of SO(4)-S decreased significantly, 2.8 and 2.3 times,
      respectively. Throughfall enrichment with base cations increased in the order Mg
      < Na < Ca < K. Using Na as a tracer ion, average dry deposition and canopy
      leaching were calculated. Leaching was the dominant process for TF enrichment by
      potassium. Leaching of base cations occurred during growing as well as dormant
      period. The calculated internal flux of Ca(2+) and Mg(2+) varied in the range of
      0.6-2.0 and 0.6-1.2 kg ha(-1) per year in spruce and pine stands, respectively.
      The internal circulation of K(+) was significantly higher (8.9-10.9 kg ha(-1) per
      year) in spruce stands than in pine stands (2.7-4.4 kg ha(-1) per year).

PMID- 16404541
TI  - Fractionation and sequential extraction of heavy metals in the soil of scrapyard
      of discarded vehicles.
AB  - Chemical and physical size fractionation of heavy metals were carried out on 20
      soil samples from the scrap yard area. Tessier method was used in sequential
      extraction. Cadmium showed the highest levels among the other elements studied in
      the exchangeable fraction (about 33%), while other elements showed low levels in
      this fraction (> or =1%). Lead and manganese were mostly found in the Fe-Mn oxide
      fraction, zinc and iron were mostly in residual fraction, while copper was mostly
      found in the organic fraction of the soil. Soil samples were size-fractionated
      into four sizes: 1000-500, 500-125, 125-53, and less than 53 microm. The highest
      levels of Fe, Cu, Pb, Mn, and Cd were found in the medium fraction (500-125 mum),
      while zinc showed its highest levels in the fine fraction (125-53 microm). The
      order of heavy metal load in the size fractions was found to be medium > fine >
      coarse > silt for Fe, Mn, Cu, Pb, and Cd, where it was found as fine > medium >
      coarse > silt for zinc.

PMID- 16404542
TI  - Evaluation of groundwater quality in northern Indo-Gangetic alluvium region.
AB  - The northern Indo-Gangetic alluvium region is known for intensive agricultural
      and industrial activities. Groundwater is the main source used for drinking,
      irrigation and industrial purposes in this region. Groundwater quality assessment
      is an essential component for its safer use. Thus, the measurements on various
      water quality parameters were carried out on surface water and groundwater
      samples of dug wells, bore wells and hand pumps at different sites spread over an
      area of about 2150 km(2). Influence of soil on hydrochemistry of groundwater was
      investigated through analyzing soil characteristics at selected sites in the
      region. Water quality classification was investigated through calculating the
      base-exchange, meteoric genesis, Langelier saturation and Ryznar stability
      indices. Groundwater sources were evaluated according to various criteria for
      their drinking and domestic, irrigation (salinity, chlorinity and sodicity), and
      industrial (saturation index) uses. Soil-water interactions and impact on
      groundwater quality was evaluated using ion flux coefficient (cf). Results of
      this study show that the groundwater in the study region is mainly of Na-HCO(3)
      and shallow meteoric water percolation type. Low cf values observed for NO(3),
      PO(4), Ca and metals indicate their lower mobility from soil matrix to
      groundwater. About 4-19% of the groundwater samples showed levels of TDS,
      hardness, alkalinity, Cl, F, SO(4), Ca, Mn, Pb, Cr and Fe above their respective
      permissible limits. Majority of samples violating the drinking water guidelines
      belong to shallow depth aquifer. Correlations between various parameters lead to
      interpretation of the results of analysis and suggesting the ionic species
      present in the groundwater sources. Contamination of some groundwater aquifers
      with F, Pb and Cr indicates natural and anthropogenic influences.

PMID- 16404543
TI  - Long term fire scar monitoring with remote sensing in Northern Namibia: relations
      between fire frequency, rainfall, land cover, fire management and trees.
AB  - A cost-effective method was developed to map fire scars on Quicklooks of Landat
      TM imagery. The method was compared with a full resolution Landsat image using
      visual interpretation and supervised classification using the Maximum Likelihood
      procedure, resulting in a high degree of agreement between methods. A long time
      series of fire scars was developed using all available Landsat Quicklooks between
      1989 and 2001 for an area of 63000 sq km in north-east Namibia. Between 27 and
      51% of the study area burned annually, while only 10% of the area did not burn
      between 1989 and 2001. Not-burned areas were mainly settled areas and permanent
      wetlands. 33% of the area burned between 5 and 7 times during the 13 years
      indicating a high frequency overall. Rainfall and livestock had little influence
      on burned areas. In 1996 formal fire management started in a portion of the study
      area consisting of building firebreaks and holding awareness programs. A
      comparison of burned areas before and after the intervention started allowed
      evaluating its effectiveness. The area where the formal fire management program
      was undertaken showed a significant decrease in burned area. It is suggested that
      awareness campaigns rather than firebreaks contributed to this decrease. Selected
      tree population data were compared with fire frequencies. Differences in tree
      occurrence, regeneration, and stem diameter distributions between low and high
      fire frequencies could be detected and explained with known responses of the
      species to fire. This suggests that the observed time series is representative of
      a long-term fire regime in the area.

PMID- 16404544
TI  - Heavy metal transport in the hindon river basin, India.
AB  - Total mass transfers of heavy metal in dissolved and particulate form has been
      determined in the downstream section of river Hindon, an important tributary of
      river Yamuna (India). The contribution of different point sources to the river
      Hindon has also been assessed. The river Kali has the largest contribution to the
      river Hindon. The highest metal loads were related to the highest flow of the
      river and thereby increased both by surface runoff and sediment resuspension. The
      contribution of monsoon months to the total transported load was also calculated
      and it was observed that monsoon months contributes more than 40% of total
      loading annually for all the metals. The metal fluxes from the river Hindon were
      compared with other rivers of Indian sub-continent.

PMID- 16404545
TI  - Relationship between micro-invertebrates and macrophytes in a wetland: Laguna
      Ibera (Corrientes, Argentina). Implications for water quality monitoring.
AB  - From November 2000 to September 2001, eight points in the Ibera lagoon were
      sampled bimonthly. At each point, pH, temperature and dissolved oxygen were
      measured and invertebrates were collected from the water around macrophytes by
      mean of a net of 180 mu m pore size. Four biotic indices were calculated and
      compared, given similar trends. The total number of taxa shows to be a good and
      simple indicator of water quality. Averaging indices across points we obtained a
      good positive correlation between indices and temperature. In this ecosystem,
      multi-habitat sampling must be used in order to obtain a good estimation of
      ecological integrity. The total number of taxa can be used for water quality
      assessment.

PMID- 16404546
TI  - Trace level determination of u, zn, cd, pb and cu in drinking water samples.
AB  - The concentration of uranium has been assessed in drinking water samples
      collected from different locations in Bathinda district, Punjab, India. The water
      samples are taken from hand pumps and tube wells. Uranium is determined using
      fission track technique. Uranium concentration in the water samples varies from
      2.23+/- 0.05 to 87.05+/- 0.29 microg/L. These values are compared with safe limit
      values recommended for drinking water. The uranium concentration in almost all
      drinking water samples is found to be more than the safe limit. Analysis of some
      heavy metals viz. Zn, Cd, Pb and Cu in water is made. The concentration of
      sodium, potassium, calcium, magnesium, chlorine and total hardness along with the
      pH value and conductivity of the water samples are measured. Some of the samples
      show stunningly high values of these parameters.

PMID- 16404547
TI  - Precision measurements from very-large scale aerial digital imagery.
AB  - Managers need measurements and resource managers need the length/width of a
      variety of items including that of animals, logs, streams, plant canopies, man
      made objects, riparian habitat, vegetation patches and other things important in
      resource monitoring and land inspection. These types of measurements can now be
      easily and accurately obtained from very large scale aerial (VLSA) imagery having
      spatial resolutions as fine as 1 millimeter per pixel by using the three new
      software programs described here. VLSA images have small fields of view and are
      used for intermittent sampling across extensive landscapes. Pixel-coverage among
      images is influenced by small changes in airplane altitude above ground level
      (AGL) and orientation relative to the ground, as well as by changes in
      topography. These factors affect the object-to-camera distance used for image
      resolution calculations. 'ImageMeasurement' offers a user-friendly interface for
      accounting for pixel-coverage variation among images by utilizing a database.
      'LaserLOG' records and displays airplane altitude AGL measured from a high
      frequency laser rangefinder, and displays the vertical velocity. 'Merge' sorts
      through large amounts of data generated by LaserLOG and matches precise airplane
      altitudes with camera trigger times for input to the ImageMeasurement database.
      We discuss application of these tools, including error estimates. We found
      measurements from aerial images (collection resolution: 5-26 mm/pixel as
      projected on the ground) using ImageMeasurement, LaserLOG, and Merge, were
      accurate to centimeters with an error less than 10%. We recommend these software
      packages as a means for expanding the utility of aerial image data.

PMID- 16404548
TI  - Heavy metal availability in soil amended with composted urban solid wastes.
AB  - A study was performed to evaluate the pH and the availability of Zn, Cu, Mn, Pb,
      and Ni in soil amended with increasing doses of composted solid wastes, collected
      in Rio de Janeiro, Rio de Janeiro State and in Coimbra, Minas Gerais State,
      Brazil. The influence of the time elapsed between compost application to the soil
      and the sampling of the plant growth substrate (soil + compost) for pH and metal
      availability analyses was also examined. The availability of heavy metals in the
      soil, in the compost and in the substrate was evaluated using DTPA solution for
      metal extraction. The increase of the compost doses added to the soil resulted in
      the increase of the pH in the substrate. The addition of the compost from the
      bigger city, Rio de Janeiro, resulted in higher increase in soil pH and available
      Zn, Cu, Pb, and Ni levels as compared to the addition of the compost from the
      smaller city, Coimbra. Increasing the time elapsed between the compost
      application to the soil and the sampling of the mixture resulted in higher
      available Zn, Cu, Mn, and Pb levels. The addition of the compost from Rio de
      Janeiro resulted in substrate metal concentrations in the order Zn > Pb > Ni > Cu
      > Mn and for the Coimbra compost the metal concentrations in the substrate was Zn
      > Pb > Cu > Ni > Mn. The higher values of pH and available metals obtained for
      the bigger city were attributed to the greatest metal contamination of its
      compost.

PMID- 16404549
TI  - Estimating air quality in a traffic tunnel using a forecasting combination model.
AB  - This study compared three forecasting methods based on their accuracy or absolute
      errors in forecasting air pollution in a traffic tunnel: the Grey model (GM), the
      Crank-Nicholson implicit scheme model, and the forecasting combination model
      (FCM). Three criteria, root mean square error (RMSE), the mean absolute error
      (MAE) and mean absolute percentage error (MAPE), were applied to the models and
      the FCM model displayed all of the characteristics of a good forecasting model.
      The correlation coefficient (r) for the FCM model equaled 0.94 (Upwind), 0.98
      (Middle) and 0.98 (Downwind). This study indicated that FCM can be used to
      accurately forecast CO pollution in the Kaohsiung Cross Harbor Tunnel.

PMID- 16404550
TI  - Using epilithic diatom communities to assess ecological condition of Xiangxi
      river system.
AB  - Assessment method for ecological condition of Xiangxi River system was studied by
      using 13 candidate metrics of epilithic diatom which can reflect conditions in
      pH, salinity, nitrogen uptake metabolism, oxygen requirements, saprobity, trophic
      state, morphological character and pollution tolerant capability etc. By one-way
      ANOVA, the metrics of relative abundance of acido-bionotic algae (ACID),
      freshwater algae (FRESH), high oxygen requirement (HIGH-O), eutraphentic state
      (EUTRA) and mobile taxa (MOBILE) were suitable for distinguishing sites in
      different conditions. Then, the river diatom index (RDI) composed of these five
      metrics was used to evaluate ecological condition of the river. The results
      showed that the healthiest sites were in the Guanmenshan Natural Reserve (with
      the mean RDI of 79.73). The sites located in tributary of Jiuchong River also
      owned excellent state (mean RDI of 78.25). Mean RDI of another tributary - Gufu
      River and the main river were 70.85 and 68.45 respectively, and the unhealthiest
      tributary was Gaolan River (with mean RDI of 65.64). The mean RDI for all the 51
      sites was 71.40. The competence of RDI was discussed with comparison of
      evaluation results of DAIpo and TDI, it can be concluded that multimetrics is
      more competent in assessment task.

PMID- 16404553
TI  - Liver-specific deletion of insulin receptor substrate 2 does not impair hepatic
      glucose and lipid metabolism in mice.
AB  - AIMS/HYPOTHESIS: Hepatic insulin resistance is thought to be a critical component
      in the pathogenesis of type 2 diabetes but the role of intrinsic insulin
      signalling pathways in the regulation of hepatic metabolism remains
      controversial. Global gene targeting in mice and in vitro studies have suggested
      that IRS2 mediates the physiological effects of insulin in the liver. Reduced
      hepatic production of IRS2 is found in many cases of insulin resistance. To
      investigate the role of IRS2 in regulating liver function in vivo, we generated
      mice that specifically lack Irs2 in the liver (LivIrs2KO). MATERIALS AND METHODS:
      Hepatic insulin signalling events were examined in LivIrs2KO mice by western
      blotting. Glucose homeostasis and insulin sensitivity were assessed by glucose
      tolerance tests and hyperinsulinaemic-euglycaemic clamp studies. The effects of
      high-fat feeding upon glucose homeostasis were also determined. Liver function
      tests were performed and expression of key metabolic genes in the liver was
      determined by RT-PCR. RESULTS: Proximal insulin signalling events and forkhead
      box O1 and A2 function were normal in the liver of LivIrs2KO mice, which
      displayed minimal abnormalities in glucose and lipid homeostasis, hepatic gene
      expression and liver function. In addition, hepatic lipid homeostasis and the
      metabolic response to a high-fat diet did not differ between LivIrs2KO and
      control mice. CONCLUSIONS/INTERPRETATION: Our findings suggest that liver IRS2
      signalling, surprisingly, is not required for the long-term maintenance of
      glucose and lipid homeostasis, and that extra-hepatic IRS2-dependent mechanisms
      are involved in the regulation of these processes.

PMID- 16404554
TI  - The rise and fall of insulin secretion in type 1 diabetes mellitus.
AB  - An understanding of the natural history of beta cell responses is an essential
      prerequisite for interventional studies designed to prevent or treat type 1
      diabetes. Here we review published data on changes in insulin responses in humans
      with type 1 diabetes. We also describe a new analysis of C-peptide responses in
      subjects who are at risk of type 1 diabetes and enrolled in the Diabetes
      Prevention Trial-1 (DPT-1). C-peptide responses to a mixed meal increase during
      childhood and through adolescence, but show no significant change during adult
      life; responses are lower in adults who progress to diabetes than in those who do
      not. The age-related increase in C-peptide responses may account for the higher
      levels of C-peptide observed in adults with newly diagnosed type 1 diabetes
      compared with those in children and adolescents. Based on these findings, we
      propose a revised model of the natural history of the disease, in which an age
      related increase in functional beta cell responses before the onset of autoimmune
      beta cell damage is an important determinant of the clinical features of the
      disease.

PMID- 16404555
TI  - Surgical treatment of hepatoblastoma in children.
AB  - Hepatoblastoma is the most common liver malignancy in children. With rare
      exceptions, complete tumour resection is required to cure the patient. Radical
      tumour resection can be obtained either with standard partial hepatectomy or
      orthotopic liver transplantation. At present, the surgical approach to
      hepatoblastoma differs significantly between treatment groups in different parts
      of the world. Our aim was to review current surgical policy in hepatoblastoma.
      All aspects of surgery in hepatoblastoma are discussed, including biopsy, tumour
      resection principles, modern achievements in the field of liver surgery, and the
      indications and potential contraindications for liver transplantation. Every
      effort should be made to resect hepatoblastoma completely either by standard
      partial hepatectomy or by the use of liver transplantation in difficult or
      clearly unresectable cases.

PMID- 16404557
TI  - Interrupted aortic arch with aberrant subclavian artery: a rare form of arch
      anomaly demonstrated with multidetector CT and 3D reconstruction.

PMID- 16404556
TI  - Hepatoblastoma: an oncological review.
AB  - The treatment of hepatoblastoma is an example of the great advances made in
      paediatric oncology over the past few decades. Formerly a disease with a dreadful
      prognosis, children now have a 5-year survival rate of over 70%. This has been
      achieved by advances in surgical techniques and the use of chemotherapy. In
      future, we hope to be able to improve survival for children with high-risk
      tumours, and decrease the morbidity associated with treatment in the others.

PMID- 16404561
TI  - Redirection of the NADH oxidation pathway in Torulopsis glabrata leads to an
      enhanced pyruvate production.
AB  - This study aimed at increasing the pyruvate productivity of a multi-vitamin
      auxotrophic yeast Torulopsis glabrata by redirecting NADH oxidation from
      adenosine triphosphate (ATP)-production pathway (oxidative phosphorylation
      pathway) to non-ATP production pathway (fermentative pathway). Two respiratory
      deficient mutants, RD-17 and RD-18, were screened and selected after ethidium
      bromide (EtBr) mutagenesis of the parent strain T. glabrata CCTCC M202019.
      Compared with the parent strain, cytochrome aa (3) and b in electron transfer
      chain (ETC) of RD-18 and cytochrome b in RD-17 were disrupted. As a consequence,
      the activities of key ETC enzymes of the mutant RD-18, including F(0)F(1)-ATP
      synthase, complex I, complex I + III, complex II + III, and complex IV, decreased
      by 22.2, 41.6, 53.1, 23.6, and 84.7%, respectively. With the deficiency of
      cytochromes in ETC, a large amount of excessive cytosolic NADH was accumulated,
      which hampered the further increase of the glycolytic flux. An exogenous electron
      acceptor, acetaldehyde, was added to the strain RD-18 culture to oxidize the
      excessive NADH. Compared with the parent strain, the concentration of pyruvate
      and the glucose consumption rate of strain RD-18 were increased by 26.5 and
      17.6%, respectively, upon addition of 2.1 mM of acetaldehyde. The strategy for
      increasing the glycolytic flux in T. glabrata by redirecting the NADH oxidation
      pathway may provide an alternative approach to enhance the glycolytic flux in
      yeast.

PMID- 16404563
TI  - Nocardiosis in a patient with primary anti-phospholipid syndrome.
AB  - Antiphospholipid syndrome is an autoimmune disease that is characterised by
      tendency to thrombosis, obstetrical and hematological complications.
      Corticosteroids may be useful for therapy of some features of this syndrome, such
      as thrombocytopenia. Nocardia is an important opportunistic infectious agent in
      immunocompromised hosts, i.e. in patients taking corticosteroids. It is important
      to be aware of these rare complications, which are correlated with the prognosis.
      In this paper, we report a patient with primary anti-phospholipid syndrome
      treated by corticosteroid, who developed disseminated nocardiosis.

PMID- 16404562
TI  - Hypercalcemia in rheumatoid arthritis: relationship with disease activity and
      bone metabolism.
AB  - To investigate the relationship between ionized calcium and disease activity,
      parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine
      (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in
      rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were
      investigated: serum levels of ionized calcium, total calcium, vitamin D
      metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3),
      intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte
      sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of
      pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of
      the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison
      with normocalcemic patients, those with hypercalcemia had significantly higher
      ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both
      iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The
      results indicate that a substantial part of RA patients is hypercalcemic.
      Hypercalcemia is associated with high disease activity and may contribute to
      suppression of PTH secretion and vitamin D hormone synthesis. High levels of
      ionized calcium may be a reflection of disease-activity-related systemic bone
      loss, and could be a predictor of BMD at the lumbar spine in RA.

PMID- 16404564
TI  - Rheumatic diseases and chronic myelogenous leukemia, presentation of four cases
      and review of the literature.
AB  - We report four patients with rheumatic disease (RD) and chronic myelogenous
      leukemia (CML). In two patients with Behcet's disease (BD) and rheumatoid
      arthritis (RA), CML developed after RD, in two patients with diffuse cutaneous
      systemic sclerosis and spondyloarthropathy, RD was diagnosed after CML. A variety
      of interactions have been described between hematological malignancies and RD.
      Nevertheless, few cases of RD have been documented associated with CML. It is
      unclear whether the development of CML in patients with RD and RD development
      after CML occurs by chance alone, is due to the underlying disease, or is
      facilitated by drugs. Whatever the cause is, it should be kept in mind that CML
      may develop in the course of RD and RD may be seen in CML patients.

PMID- 16404565
TI  - Multiphasic multidetector-row CT (MDCT) in detection and staging of transitional
      cell carcinomas of the upper urinary tract.
AB  - The aim of this study was to evaluate the potential of multiphasic multidetector
      row CT (MDCT) in the detection and staging of transitional cell carcinomas (TCC)
      of the upper urinary tract. We performed a retrospective chart review of 39
      consecutive patients with 41 histologically verified TCC of the renal pelvis
      and/or the ureter. The urinary tract was examined using MDCT performing
      unenhanced and contrast-enhanced scans during the corticomedullary (CMP),
      nephrographic (NP) and pyelographic phase (PP). Tumors were staged according to
      the TNM classification. MDCT and histopathological findings were correlated. The
      attenuation of the lesions was documented in Hounsfield units (HU). In MDCT, all
      41 TCC--including two multicentric TCC--were detected. TCC confined to the organ
      (stage 0a-II) was correctly staged in 28/29 tumors (96.6%). Stage III-IV tumors
      were correctly staged in 8/12 patients (66.6%). Overall, MDCT was accurate in
      predicting pathologic TNM stage in 36/41 upper urinary tract TCC (87.8%). There
      was no significant difference of mean attenuation of TCC between CMP, NP and PP
      (P > 0.05). MDCT with its high spatial and temporal resolution is an accurate
      tool for detection TCC of the upper urinary tract, with 87.8% accuracy in
      predicting its stage.

PMID- 16404566
TI  - Direct detector radiography versus dual reading computed radiography: feasibility
      of dose reduction in chest radiography.
AB  - The image quality of dual-reading computed radiography and dose-reduced direct
      radiography of the chest was compared in a clinical setting. The study group
      consisted of 50 patients that underwent three posteroanterior chest radiographs
      within minutes, one image obtained with a dual read-out computed radiography
      system (CR; Fuji 5501) at regular dose and two images with a flat panel direct
      detector unit (DR; Diagnost, Philips). The DR images were obtained with the same
      and with 50% of the dose used for the CR images. Images were evaluated in a
      blinded side-by-side comparison. Eight radiologists ranked the visually
      perceivable difference in image quality using a three-point scale. Then, three
      radiologists scored the visibility of anatomic landmarks in low and high
      attenuation areas and image noise. Statistical analysis was based on Friedman
      tests and Wilcoxon rank sum tests at a significance level of P<0.05. DR was
      judged superior to CR for the delineation of structures in high attenuation areas
      of the mediastinum even when obtained with 50% less dose (P<0.001). The
      visibility of most pulmonary structures was judged equivalent with both
      techniques, regardless of acquisition dose and speed level. Scores for image
      noise were lower for DR compared with CR, with the exception of DR obtained at a
      reduced dose. Thus, in this clinical preference study, DR was equivalent or even
      superior to the most modern dual read-out CR, even when obtained with 50% dose. A
      further dose reduction does not appear to be feasible for DR without significant
      loss of image quality.

PMID- 16404567
TI  - The effect of IHF on sigmaS selectivity of the phoA and pst promoters of
      Escherichia coli.
AB  - The pst operon, a member of the PHO regulon of Escherichia coli, encodes a high
      affinity phosphate transport system whose expression is induced when the cells
      enter a phase of phosphate starvation. The expression of pst is stimulated by the
      integration host factor (IHF). Transcription of the PHO regulon genes is
      initiated by the RNA polymerase complexed with sigma (D) (Esigma (D)). Owing to a
      cytosine residue at position -13 of the pst promoter its transcription can also
      be initiated by Esigma (S). Here, we show that inactivation of IHF in vivo
      abolishes the sigma (S)-dependent transcription initiation of the pst operon,
      indicating that both -13C residue and IHF are required to confer on pst the
      ability to be transcribed by Esigma (S). Introduction of a -13C residue in the
      promoter region of phoA, another PHO regulon gene that is not directly affected
      by IHF, did not affect its exclusive transcription initiation by Esigma (D).

PMID- 16404569
TI  - Global gene regulation in Yersinia enterocolitica: effect of FliA on the
      expression levels of flagellar and plasmid-encoded virulence genes.
AB  - This study describes the involvement of the sigma factor of the flagellar system,
      FliA, in global gene regulation of Yersinia enterocolitica. In addition to
      exhibiting a positive effect upon the expression levels of eight class III
      flagellar operons, FliA also exhibited a negative effect upon the expression
      levels of four virulence operons that are located on the pYV virulence plasmid.
      These are yadA, virC, yopQ, and the insertion element ISYen1. While the positive
      effect on class III flagellar operons by FliA is most likely direct, the negative
      effect on the virulence operons appears to require the known transcriptional
      activator of these genes, VirF. This was determined using microarray analysis,
      quantitative PCR and a search for putative binding sites for FliA. In addition to
      the FliA regulation of flagellar and plasmid-encoded virulence genes, we studied
      temperature regulation of these genes. While wild-type cells exhibited increased
      expression levels of flagellar genes and decreased expression levels of plasmid
      encoded virulence genes at 25 degrees C (as compared to 37 degrees C),
      temperature dependence of gene expression was much reduced in the fliA mutants.
      We conclude that FliA contributes to the inverse temperature regulation of
      flagellar and plasmid-encoded virulence genes. We present a network of
      transcriptional regulation around FlhD/FlhC and FliA.

PMID- 16404568
TI  - Pelotomaculum terephthalicum sp. nov. and Pelotomaculum isophthalicum sp. nov.:
      two anaerobic bacteria that degrade phthalate isomers in syntrophic association
      with hydrogenotrophic methanogens.
AB  - An anaerobic phthalate isomer-degrading strain (JT(T)) that we previously
      isolated was characterized. In addition, a strictly anaerobic, mesophilic,
      syntrophic phthalate isomer-degrading bacterium, designated strain JI(T), was
      isolated and characterized in this study. Both were non-motile rods that formed
      spores. In both strains, the optimal growth was observed at temperatures around
      37 degrees C and neutral pH. In syntrophic co-culture with the hydrogenotrophic
      methanogen Methanospirillum hungatei, both strains could utilize two or three
      phthalate isomers for growth, and produce acetate and methane as end products.
      Strain JT(T) was able to grow on isophthalate, terephthalate, and a number of low
      molecular weight aromatic compounds, such as benzoate, hydroquinone, 2
      hydroxybenzoate, 3-hydroxybenzoate, 2,5-dihydroxybenzoate, 3-phenylpropionate in
      co-culture with M. hungatei. It could also grow on crotonate, hydroquinone and
      2,5-dihydroxybenzoate in pure culture. Strain JI(T) utilized all of the three
      phthalate isomers as well as benzoate and 3-hydroxybenzoate for growth in co
      culture with M. hungatei. No substrates were, however, found to support the
      axenic growth of strain JI(T). Neither strain JT(T) nor strain JI(T) could
      utilize sulfate, sulfite, thiosulfate, nitrate, fumarate, Fe (III) or 4
      hydroxybenzoate as electron acceptor. Phylogenetically, strains JT(T) and JI(T)
      were relatively close to the members of the genera Pelotomaculum and
      Cryptanaerobacter in 'Desulfotomaculum lineage I'. Physiological and
      chemotaxonomic characteristics indicated that the two isolates should be
      classified into the genus Pelotomaculum, creating two novel species for them.
      Here, we propose Pelotomaculum terephthalicum sp. nov. and Pelotomaculum
      isophthalicum sp. nov. for strain JT(T) and strain JI(T), respectively. The type
      strains are strains JT(T) (= DSM 16121(T )= JCM 11824(T )= NBRC 100523(T)) and
      JI(T) (= JCM 12282(T) = BAA-1053(T)) for P. terephthalicum and P. isophthalicum,
      respectively.

PMID- 16404570
TI  - Rapid pleurodesis with doxycycline through a small-bore catheter for the
      treatment of metastatic malignant effusions.
AB  - GOALS OF WORK: The goal of the study was to evaluate the safety and efficacy of
      bedside pleurodesis with doxycycline using a short-term indwelling chest catheter
      for the palliative treatment of malignant effusions. MATERIALS AND METHODS: A
      prospective study of 36 rapid pleurodesis procedures in 34 patients with
      malignant pleural effusions was conducted over a 5-year period in a university
      hospital. A 12F chest catheter placement was facilitated utilizing the Seldinger
      percutaneous entry technique. Patients received 500 mg of intrapleural
      doxycycline combined in half of the cases with mepivacaine. We assessed success
      or failure of pleurodesis in addition to the frequency of complications and
      survival. MAIN RESULTS: Chest tubes were removed within 24 h in 69% and within 48
      h in 94% of the patients. Complete success of pleurodesis was achieved in 17
      (55%), partial success in eight (26%), and failure in six (19%) out of 31
      evaluative procedures. Thus, the overall success rate of pleurodesis was 81%.
      Toxicity was mild and included pain (36%), fever (8%), and pneumothorax (6%). The
      median survival was 105 days. There was no relationship between instillation of
      intrapleural anesthetics and development of pain. CONCLUSIONS: Rapid pleurodesis
      with doxycycline, which can be accomplished within 24 to 48 h, is a valid option
      for the symptomatic treatment of malignant effusions. This technique can be used
      as a first-line procedure in the majority of cases, particularly if thoracoscopic
      facilities are not available.

PMID- 16404572
TI  - Two Hrd1p homologues in the yeast Yarrowia lipolytica which act in different
      pathways.
AB  - The endoplasmic reticulum associated degradation (ERAD) is a process widespread
      in eukaryotes that enable cells to get rid of unfolded or unassembled
      polypeptides which jam the endoplasmic reticulum compartment. In order to improve
      understanding of the initial steps of the secretory pathway and their
      relationship, we focused on components of the ERAD ubiquitylation machinery in
      the yeast Yarrowia lipolytica. Two Hrd1p homologues, Hrd1p and Hrh1p, were
      identified in Y. lipolytica. A study of the fate of the heterologous CPY*
      reporter protein showed that YlHrd1p is involved in the elimination of this
      misfolded polypeptide, while YlHrh1p is not. Moreover, the different phenotypic
      pattern displayed by Deltahrd1 and Deltahrh1 cells suggests that the two putative
      E3 enzymes function in separate ways. Our results bring some evidence of a
      coupling between the ERAD pathway and the co-translational translocation process
      and show that studies in Y. lipolytica can give new insights into events that
      take place in the ER.

PMID- 16404571
TI  - Characterization of hns genes from Erwinia amylovora.
AB  - The small basic histone-like protein H-NS is known for bacteria to attenuate
      virulence of several animal pathogens. An hns homologue from E. amylovora was
      identified by complementing an E. coli hns-mutant strain with a cosmid library
      from E. amylovora. A 1.6 kb EcoRI-fragment complemented the mucoid phenotype and
      repressed the ss-glucosidase activity of E. coli PD32. The open reading frame
      encoding an H-NS-like protein of 134 amino acid was later shown to be located on
      plasmid pEA29 (McGhee and Jones 2000). A chromosomal hns gene was amplified with
      PCR consensus primers and localized near galU of E. amylovora. E. amylovora
      mutants were created by insertion of a resistance cassette, and the intact gene
      was inserted into a high copy number plasmid for constitutive expression.
      Purified chromosomal H-NS protein preferentially bound to a DNA fragment from the
      lsc region and bending was predicted for an adjacent fragment with the rlsB
      promoter. Levan production was significantly increased by hns mutations.
      Synthesis of the capsular exopolysaccharide amylovoran and of levan were reduced,
      when hns from the E. amylovora plasmid was overexpressed. A mutation in
      chromosomal hns of E. amylovora increased amylovoran synthesis, and both
      mutations retarded symptom formation on immature pears.

PMID- 16404573
TI  - Immunohistochemical and in situ hybridization analysis of galectin-3, a beta
      galactoside binding lectin, in the urinary system of adult mice.
AB  - Galectin is an animal lectin that has high affinity to beta-galactoside of
      glycoconjugates. In the present study, cellular expression of galectin subtypes
      in the urinary system of adult mice was examined by in situ hybridization and
      immunohistochemistry. The major subtype expressed in the murine urinary system
      was galectin-3, which was expressed continuously from the kidney to the distal
      end of the urethra. The renal cortex expressed galectin-3 more intensely than the
      medulla. Renal galectin-3 immunoreactivity was strongest in the cortical
      collecting ducts, where principal cells were the sole cellular source. All cell
      layers of the transitional epithelium from the renal pelvis to the urethra
      strongly expressed galectin-3 at the mRNA and protein levels. An electron
      microscopic study demonstrated diffuse cytoplasmic localization of galectin-3 in
      principal cells of the collecting ducts and in the bladder epithelial cells.
      Urethral galectin-3 expression at the pars spongiosa decreased in intensity near
      the external urethral orifice, where the predominant subtype of galectin was
      substituted by galectin-7. The muscular layer of the ureter and urinary bladder
      contained significant signals for galectin-1. Taken together, the observations
      indicate that the adult urinary system shows intense and selective expression of
      galectin-3 in epithelia of the uretic bud- and cloaca-derivatives.

PMID- 16404575
TI  - Transgenic modification of gai or rgl1 causes dwarfing and alters gibberellins,
      root growth, and metabolite profiles in Populus.
AB  - In Arabidopsis and other plants, gibberellin (GA)-regulated responses are
      mediated by proteins including GAI, RGA and RGL1-3 that contain a functional
      DELLA domain. Through transgenic modification, we found that DELLA-less versions
      of GAI (gai) and RGL1 (rgl1) in a Populus tree have profound, dominant effects on
      phenotype, producing pleiotropic changes in morphology and metabolic profiles.
      Shoots were dwarfed, likely via constitutive repression of GA-induced elongation,
      whereas root growth was promoted two- to threefold in vitro. Applied GA(3
      )inhibited adventitious root production in wild-type poplar, but gai/rgl1 poplars
      were unaffected by the inhibition. The concentrations of bioactive GA(1) and
      GA(4) in leaves of gai- and rgl1-expressing plants increased 12- to 64-fold,
      while the C(19) precursors of GA(1) (GA(53), GA(44) and GA(19)) decreased three-
      to ninefold, consistent with feedback regulation of GA 20-oxidase in the
      transgenic plants. The transgenic modifications elicited significant metabolic
      changes. In roots, metabolic profiling suggested increased respiration as a
      possible mechanism of the increased root growth. In leaves, we found metabolite
      changes suggesting reduced carbon flux through the lignin biosynthetic pathway
      and a shift towards allocation of secondary storage and defense metabolites,
      including various phenols, phenolic glucosides, and phenolic acid conjugates.

PMID- 16404574
TI  - Genetic and biochemical evidence for involvement of HOTHEAD in the biosynthesis
      of long-chain alpha-,omega-dicarboxylic fatty acids and formation of
      extracellular matrix.
AB  - In plants, extracellular matrix polymers built from polysaccharides and cuticular
      lipids have structural and protective functions. The cuticle is found to be ten
      times thinner in Arabidopsis thaliana (L.) Heynh than in many other plants, and
      there is evidence that it is unusual in having a high content of alpha-,omega
      dicarboxylic fatty acids (FAs) in its polyesters. We designated the new organ
      fusion mutant hth-12 after it appeared to be allelic to adhesion of calyx edges
      (ace) and hothead (hth), upon molecular cloning of the gene by transposon
      tagging. This mutant is deficient in its ability to oxidize long-chain omega
      hydroxy FAs to omega-oxo FAs, which results in leaf polyesters in decreased alpha
      ,omega-dicarboxylic FAs and increased omega-hydroxy FAs. These chemical
      phenotypes lead to disorder of the cuticle membrane structure in hth-12. ACE/HTH
      is a single-domain protein showing sequence similarity to long-chain FA omega
      alcohol dehydrogenases from Candida species, and we hypothesize that it may
      catalyze the next step after cytochrome P450 FA omega-hydroxylases in the omega
      oxidation pathway. We show that ACE/HTH is specifically expressed in epidermal
      cells. It appears very likely therefore that the changes in the amount of alpha
      ,omega-dicarboxylic FAs in hth-12 reflect the different composition of cuticular
      polyesters. The ACE/HTH gene is also expressed in root epidermal cells which do
      not form a polyester membrane on the exterior surface, thereby making it possible
      that the end products of the pathway, alpha-,omega-dicarboxylic FAs, are
      generally required for the cross-linking that ensures the integrity of the outer
      epidermal cell wall.

PMID- 16404576
TI  - Volatiles released from bean plants in response to agromyzid flies.
AB  - Liriomyza sativae Blanchard and Liriomyza huidobrensis (Blanchard) (Diptera:
      Agromyzidae) are two invasive flies in China that have caused economical damage
      on vegetables and ornamental plants. In this article, we report the profiles of
      emitted volatiles from healthy, mechanically damaged, and leafminer-damaged bean,
      Phaseolus vulgaris L., plants. Among 25 emitted volatiles identified, (E)-2-hexen
      1-al, (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), (Z)-3-hexenyl acetate, (Z)-3
      hexen-1-ol, (syn)- and (anti)-2-methylpropanal oxime, (syn)-2-methylbutanal
      oxime, linalool, and (E,E)-alpha-farnesene were consistently released from
      damaged bean plants. Combined amounts of these nine compounds made up more than
      70% of the total volatiles emitted from each treatment. No qualitative
      differences in volatile emission were found between bean plants damaged by the
      two fly species; however, amounts of several major compounds induced by L.
      huidobrensis damage were significantly higher than those from plants damaged by
      L. sativae. The mechanically damaged plants released a higher proportion of green
      leaf volatiles than plants in the other treatments, whereas leafminer-damaged
      plants produced more terpenoids and oximes. Furthermore, the volatile profiles
      emitted from plants, damaged by adult leafminers, by second instar larvae, and
      even the plants with empty mines left by leafminer larvae (the pupal stage) were
      significantly different. The identification of volatile oximes released from
      damaged plants was confirmed and is discussed in a behavioral and biological
      control context.

PMID- 16404577
TI  - Arabinoxylan and (1-->3),(1-->4)-beta-glucan deposition in cell walls during
      wheat endosperm development.
AB  - Arabinoxylans (AX) and (1-->3),(1-->4)-beta-glucans are major components of wheat
      endosperm cell walls. Their chemical heterogeneity has been described but little
      is known about the sequence of their deposition in cell walls during endosperm
      development. The time course and pattern of deposition of the (1-->3) and (1-
      >3),(1-->4)-beta-glucans and AX in the endosperm cell walls of wheat (Triticum
      aestivum L. cv. Recital) during grain development was studied using specific
      antibodies. At approximately 45 degrees D (degree-days) after anthesis the
      developing walls contained (1-->3)-beta-glucans but not (1-->3),(1-->4)-beta
      glucans. In contrast, (1-->3),(1-->4)-beta-glucans occurred widely in the walls
      of maternal tissues. At the end of the cellularization stage (72 degrees D), (1-
      >3)-beta-glucan epitopes disappeared and (1-->3),(1-->4)-beta-glucans were found
      equally distributed in all thin walls of wheat endosperm. The AX were detected at
      the beginning of differentiation (245 degrees D) in wheat endosperm, but were
      missing in previous stages. However, epitopes related to AX were present in
      nucellar epidermis and cross cells surrounding endosperm at all stages but not
      detected in the maternal outer tissues. As soon as the differentiation was
      apparent, the cell walls exhibited a strong heterogeneity in the distribution of
      polysaccharides within the endosperm.

PMID- 16404578
TI  - Cell-wall structure and anisotropy in procuste, a cellulose synthase mutant of
      Arabidopsis thaliana.
AB  - In dark-grown hypocotyls of the Arabidopsis procuste mutant, a mutation in the
      CesA6 gene encoding a cellulose synthase reduces cellulose synthesis and severely
      inhibits elongation growth. Previous studies had left it uncertain why growth was
      inhibited, because cellulose synthesis was affected before, not during, the main
      phase of elongation. We characterised the quantity, structure and orientation of
      the cellulose remaining in the walls of affected cells. Solid-state NMR
      spectroscopy and infrared microscopy showed that the residual cellulose did not
      differ in structure from that of the wild type, but the cellulose content of the
      prc-1 cell walls was reduced by 28%. The total mass of cell-wall polymers per
      hypocotyl was reduced in prc-1 by about 20%. Therefore, the fourfold inhibition
      of elongation growth in prc-1 does not result from aberrant cellulose structure,
      nor from uniform reduction in the dimensions of the cell-wall network due to
      reduced cellulose or cell-wall mass. Cellulose orientation was quantified by two
      quantitative methods. First, the orientation of newly synthesised microfibrils
      was measured in field-emission scanning electron micrographs of the cytoplasmic
      face of the inner epidermal cell wall. The ordered transverse orientation of
      microfibrils at the inner face of the cell wall was severely disrupted in prc-1
      hypocotyls, particularly in the early growth phase. Second, cellulose orientation
      distributions across the whole cell-wall thickness, measured by polarised
      infrared microscopy, were much broader. Analysis of the microfibril orientations
      according to the theory of composite materials showed that during the initial
      growth phase, their anisotropy at the plasma membrane was sufficient to explain
      the anisotropy of subsequent growth.

PMID- 16404579
TI  - Non-lethal freezing effects on seed degreening in Brassica napus.
AB  - The effects of a non-lethal freezing stress on chlorophyll content, moisture
      level and distribution, and abscisic acid (ABA) levels were examined in siliques
      and seeds of Brassica napus (canola). A non-lethal freezing stress resulted in
      the retention of chlorophyll in seed at harvest that was most pronounced for
      seeds 28, 32 and 36 days after flowering (DAF). This increase was primarily due
      to an increased retention of chlorophyll a relative to chlorophyll b. Chlorophyll
      retention in seeds exposed to a non-lethal freezing stress correlated with an
      increased ABA catabolism, as measured 1, 3 or 7 days after the stress treatment.
      Although the non-lethal freezing stress had no significant effect on moisture
      content in seeds of siliques stressed at 28-44 DAF, moisture distribution, as
      viewed by magnetic resonance imaging, showed an uneven drying of 32 and 40 DAF
      siliques after exposure to the non-lethal freezing stress. Moisture was initially
      lost more rapidly from the silique wall between seeds, than in control non
      stressed siliques. Increased moisture loss was not due to structural changes in
      the vasculature of the silique/seed of stressed tissues. These results are
      consistent with the hypothesis that a non-lethal freezing stress-induced decrease
      in ABA level, during seed maturation, effects an inhibition of normal chlorophyll
      a catabolism resulting in mature but green B. napus seed.

PMID- 16404581
TI  - Transgenic rice expressing Allium sativum leaf lectin with enhanced resistance
      against sap-sucking insect pests.
AB  - Mannose binding Allium sativum leaf agglutinin (ASAL) has been shown to be
      antifeedant and insecticidal against sap-sucking insects. In the present
      investigation, ASAL coding sequence was expressed under the control of CaMV35S
      promoter in a chimeric gene cassette containing plant selection marker, hpt and
      gusA reporter gene of pCAMBIA1301 binary vector in an elite indica rice cv. IR64.
      Many fertile transgenic plants were generated using scutellar calli as initial
      explants through Agrobacterium-mediated transformation technology. GUS activity
      was observed in selected calli and in mature plants. Transformation frequency was
      calculated to be approximately 12.1%+/-0.351 (mean +/- SE). Southern blot
      analyses revealed the integration of ASAL gene into rice genome with a
      predominant single copy insertion. Transgene localization was detected on
      chromosomes of transformed plants using PRINS and C-PRINS techniques. Northern
      and western blot analyses determined the expression of transgene in transformed
      lines. ELISA analyses estimated ASAL expression up to 0.72 and 0.67% of total
      soluble protein in T0 and T1 plants, respectively. Survival and fecundity of
      brown planthopper and green leafhopper were reduced to 36% (P < 0.01), 32% (P <
      0.05) and 40.5, 29.5% (P < 0.001), respectively, when tested on selected plants
      in comparison to control plants. Specific binding of expressed ASAL to receptor
      proteins of insect gut was analysed. Analysis of T1 progenies confirmed the
      inheritance of the transgenes. Thus, ASAL promises to be a potential component in
      insect resistance rice breeding programme.

PMID- 16404582
TI  - [Analgesia of the axilla using a paravertebral catheter in the lamina technique].
AB  - A 62-year-old female suffered from therapy-resistant pain in the axilla after
      lymphadenectomy. The pain ranged from 8-10 on the numeric rating scale (NRS)
      despite multimodal pain therapy (non-steroid anti-rheumatics, opioids,
      physiotherapy, acupuncture). A paravertebral trial injection was performed
      preoperatively on the laminae of the thoracic vertebrae Th 2-Th 4. As the patient
      responded well, a paravertebral catheter was inserted close to Th 4 directly
      before the revision operation took place the following day. The case study
      describes the possibilities of eliminating pain segmentally in the axilla and an
      alternative technique to a paravertebral block (lamina technique).

PMID- 16404580
TI  - Expression of SK3-type dehydrin in transporting organs is associated with cold
      acclimation in Solanum species.
AB  - The expression of a gene, encoding a dehydrin protein designated as DHN24 was
      analyzed at the protein level in two groups of Solanum species differing in cold
      acclimation ability. The DHN24 protein displays consensus amino acid sequences of
      dehydrins, termed K- and S-segments. The S-segment precedes three K-segments,
      classifying the protein into SK3-type dehydrins. A group of Solanum species able
      to cold acclimation constituted by S. sogarandinum and S. tuberosum, cv. Aster,
      and a second one composed of a S. sogarandinum line, that lost ability to cold
      acclimation, and of S. tuberosum, cv. Irga, displaying low ability to cold
      acclimation were studied. Under control conditions, noticeable levels of the
      DHN24 protein was observed in stems, tubers, and roots of Solanum species. No
      protein was detected in leaves. During low temperature treatment the DHN24
      protein level substantially increased in tubers, in transporting organs and in
      apical parts, and only a small increase was observed in leaves. The increase in
      protein abundance was only observed in the plants able to cold acclimate and was
      found to parallel the acclimation capacity. Upon drought stress, the DHN24 level
      decreased in stems and in leaves, but increased in apical parts. These results
      suggest that Dhn24 expression is regulated by organ specific factors in the
      absence of stress and by factors related to cold acclimation processes during low
      temperature treatment in collaboration with organ-specific factors. A putative
      function of the SK3-type dehydrin proteins during plant growth and in the
      tolerance to low temperature is discussed.

PMID- 16404583
TI  - TRIM retrotransposons occur in apple and are polymorphic between varieties but
      not sports.
AB  - Retrotransposon markers have been demonstrated to be powerful tools for
      investigating linkage, evolution and genetics diversity in plants. In the present
      study, we identified and cloned three full-size TRIM (terminal-repeat
      retrotransposon in miniature) group retrotransposon elements from apple (Malus
      domestica) cv. 'Antonovka', the first from the Rosaceae. To investigate their
      utility as markers, we designed primers to match the long terminal repeats (LTRs)
      of the apple TRIM sequences. We found that PCR reactions with even a single
      primer produced multiple bands, suggesting that the copy number of these TRIM
      elements is relatively high, and that they may be locally clustered or nested in
      the genome. Furthermore, the apple TRIM primers employed in IRAP (inter
      retrotransposon amplified polymorphism) or REMAP (retrotransposon-microsatellite
      amplified polymorphism) analyses produced unique, reproducible profiles for 12
      standard apple cultivars. On the other hand, all seven of the sport mutations in
      this study were identical to their mother cultivar. Genetic similarity values
      calculated from the IRAP/REMAP analyses or the STMS (sequence tagged
      microsatellite sites) analysis were generally comparable. PAUP cluster analysis
      based on IRAP and REMAP markers in apple and Japanese quince generated an NJ tree
      that is in good accordance with both a tree based on SMTS markers and the origin
      of the studied samples. Our results demonstrate that, although they do not encode
      the proteins necessary to carry out a life cycle and are thereby non-autonomous,
      TRIMs are at least as polymorphic in their insertion patterns as conventional
      complete retrotransposons.

PMID- 16404584
TI  - Development of four phylogenetically-arrayed BAC libraries and sequence of the
      APA locus in Phaseolus vulgaris.
AB  - The APA family of seed proteins consists of three subfamilies, in evolutionary
      order of hypothesized appearance: phytohaemagglutinins (PHA), alpha-amylase
      inhibitors (alphaAI), and arcelins (ARL). The APA family plays a defensive role
      against mammalian and insect seed predation in common bean (Phaseolus vulgaris
      L.). The main locus (APA) for this gene family is situated on linkage group B4.
      In order to elucidate the pattern of duplication and diversification at this
      locus, we developed a BAC library in each of four different Phaseolus genotypes
      that represent presumptive steps in the evolutionary diversification of the APA
      family. Specifically, BAC libraries were established in one P. lunatus (cv.
      'Henderson: PHA+ alphaAI- ARL-) and three P. vulgaris accessions (presumed
      ancestral wild G21245 from northern Peru: PHA+ alphaAI+ ARL-; Mesoamerican wild
      G02771: PHA+ alphaAI+ ARL+; and Mesoamerican breeding line BAT93: PHA+ alphaAI+
      ARL-). The libraries were constructed after HindIII digestion of high molecular
      weight DNA, obtained with a novel nuclei isolation procedure. The frequency of
      empty or cpDNA-sequence-containing clones in all libraries is low (generally
      <1%). The Henderson, G21245, and G02771 libraries have a 10x genome coverage,
      whereas the BAT93 library has a 20x coverage to allow further, more detailed
      genomic analysis of the bean genome. The complete sequence of a 155 kbp-insert
      clone of the G02771 library revealed six sequences belonging to the APA gene
      family, including members of the three subfamilies, as hypothesized. The
      different subfamilies were interspersed with retrotransposon sequences. In
      addition, other sequences were identified with similarity to chloroplast DNA, a
      dehydrin gene, and the Arabidopsis flowering D locus. Linkage between the
      dehydrin gene and the D1711 RFLP marker identifies a potential syntenic region
      between parts of common bean linkage group B4 and cowpea linkage group 2.

PMID- 16404585
TI  - Genetic mapping of a major gene affecting onion bulb fructan content.
AB  - The non-structural dry matter content of onion bulbs consists principally of
      fructose, glucose, sucrose and fructans. The objective of this study was to
      understand the genetic basis for the wide variation observed in the relative
      amounts of these carbohydrates. Bulb carbohydrate composition was evaluated in
      progeny from crosses between high dry matter storage onion varieties and sweet,
      low dry matter varieties. When samples were analysed on a dry weight basis,
      reducing sugar and fructan content exhibited high negative correlations and
      bimodal segregation suggestive of the action of a major gene. A polymorphic SSR
      marker, ACM235, was identified which exhibited strong disequilibrium with bulb
      fructan content in F(2:3) families from the 'W202A' x 'Texas Grano 438' mapping
      population evaluated in two environments. This marker was mapped to chromosome 8
      in the interspecific population 'Allium cepa x A. roylei'. Mapping in the
      'Colossal Grano PVP' x 'Early Longkeeper P12' F2 population showed that a
      dominant major gene conditioning high-fructan content lay in the same genomic
      region. QTL analysis of total bulb fructan content in the intraspecific mapping
      population 'BYG15-23' x 'AC43' using a complete molecular marker map revealed
      only one significant QTL in the same chromosomal region. This locus,
      provisionally named Frc, may account for the major phenotypic differences in bulb
      carbohydrate content between storage and sweet onion varieties.

PMID- 16404587
TI  - On the utility of data from the International HapMap Project for Australian
      association studies.
AB  - We compare patterns of linkage disequilibrium (LD) for 633 SNPs in two regions
      between samples collected in two Australian states and HapMap samples collected
      from Utah residents of Northern and Western (NW) European ancestry (CEU).
      Patterns of LD in the Australian and HapMap samples are similar, and tag SNPs
      chosen using HapMap genotypes perform almost as well on Australian samples as
      tags chosen using Australian genotypes.

PMID- 16404586
TI  - A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial
      dysostosis.
AB  - Weyers acrofacial dysostosis (MIM 193530) is an autosomal dominant disorder
      clinically characterized by mild short stature, postaxial polydactyly, nail
      dystrophy and dysplastic teeth. Ellis-van Creveld syndrome (EvC, MIM 225500) is
      an autosomal recessive disorder with a similar, but more severe phenotype.
      Mutations in the EVC have been identified in both syndromes. However, the EVC
      mutations only occur in a small proportion of EvC patients. Recently, mutations
      in a new gene, EVC2, were found to be associated with other EvC cases. The EVC
      and EVC2 are located close to each other in a head-to-head configuration and may
      be functionally related. In this study, we report identification of a novel
      heterozygous deletion in the EVC2 that is responsible for autosomal dominant
      Weyers acrofacial dysostosis in a large Chinese family. This constitutes the
      first report of Weyers acrofacial dysostosis caused by this gene. Hence, the
      spectrum of malformation syndromes due to EVC2 mutations is further extended. Our
      data provides conclusive evidence that Weyers acrofacial dysostosis and EvC
      syndrome are allelic and genetically heterogeneous conditions.

PMID- 16404588
TI  - Analysis of coordinated circling and linear flights of a lycaenid butterfly
      species.
AB  - Circling and linear flights of a hairstreak Chrysozephyrus smaragdinus were
      recorded in natural habitat with a high-speed video camera. Circling flight paths
      were resolved into rotation and shift components; values on X- and Y-coordinates
      of the butterfly position were separately extracted against time and fitted with
      a regression line composed of a sinusoidal curve and a linear line. From the
      obtained parameters, diameter, rotation number, and flight velocity were
      calculated. Flapping movements were also analyzed. Two types of circling flights,
      horizontal and vertical, were discriminated. In both flights, the rotation
      diameter was about 10 cm, rotation number of 3/s, flight velocity of 0.9 m/s, and
      wing-beat frequency of 20/s. The coordination of paired butterflies in circling
      flight showed a higher correlation in the horizontal circling flight. In the
      vertical circling flight, butterflies accelerated the downstroke speed of the
      wing in the ascending phase. They flew about four times faster in linear flights
      than in circling flights due to the higher frequency of wing beats.

PMID- 16404589
TI  - Choosy males from the underground: male mating preferences in surface- and cave
      dwelling Atlantic mollies (Poecilia mexicana).
AB  - Atlantic mollies (Poecilia mexicana) inhabit a variety of surface habitats, but
      they also occur in a sulfur cave in southern Mexico. We examined male mate choice
      relative to female body size in the cave population and in the most closely
      related surface-dwelling population from a nearby river. Males from both
      populations were either light- or dark-reared and could choose between two
      differently sized females either on the basis of visual cues in light or on the
      basis of solely nonvisual cues in darkness. Sexual preferences were estimated
      from the degree of association. Cave molly males always showed a preference for
      the larger female, both in light and in darkness. Among the surface males, only
      light-reared males showed a preference in the visual cues test, but not in
      darkness. In a control experiment, we demonstrated that male association
      preferences directly translate into actual mating preferences. Apparently, using
      visual cues for mate choice is the ancestral state in this system, and using
      nonvisual cues has evolved as a novel trait in the cave population. We discuss
      the evolution of nonvisual male mate choice in the context of changed
      environmental conditions, namely the absence of light, hypoxia, and toxic
      hydrogen sulfide in the cave.

PMID- 16404590
TI  - Metal binding in amyloid beta-peptides shows intra- and inter-peptide
      coordination modes.
AB  - X-ray absorption spectroscopy data show different metal binding site structures
      in beta-amyloid peptides according to whether they are complexed with Cu(2+) or
      Zn(2+) ions. While the geometry around copper is stably consistent with an intra
      peptide binding with three metal-coordinated Histidine residues, the zinc
      coordination mode depends on specific solution conditions. In particular,
      different sample preparations are seen to lead to different geometries around the
      absorber that are compatible with either an intra- or an inter-peptide
      coordination mode. This result reinforces the hypothesis that assigns different
      physiological roles to the two metals, with zinc favoring peptide aggregation
      and, as a consequence, plaque formation.

PMID- 16404591
TI  - An iterative method to calculate forces exerted by single cells and multicellular
      assemblies from the detection of deformations of flexible substrates.
AB  - We present a new method for quantification of traction forces exerted by
      migrating single cells and multicellular assemblies from deformations of flexible
      substrate. It is based on an iterative biconjugate gradient inversion method. We
      show how the iteration and the solution are influenced by experimental parameters
      such as the noise on deformations sigma ( XY ), and the mean depth of recorded
      deformations Z (M). In order to find the validity range of our computational
      method, we simulated two different patterns of force. The first artificial force
      pattern mimics the forces exerted by a migrating Dictyostelium slug at a spatial
      resolution of Delta=20 mum (Rieu et al. in Biophys J 89:3563-3576, 2005) and
      corresponds to a large and spread force field. The second simulated force pattern
      mimics forces exerted by a polarized fibroblast at discrete focal adhesion sites
      separated by Delta=4 microm. Our iterative method allows, without using explicit
      regularization, the detailed reconstruction of the two investigated patterns when
      noise is not too high (sigma ( XY )/u (max)< or =6%, where u (max )is the maximal
      deformation), and when the plane of recorded deformations is close to the surface
      (Delta/Z (M)> or =4). The method and the required range of parameters are
      particularly suitable to study forces over large fields such as those observed in
      multicellular assemblies.

PMID- 16404592
TI  - Calcium regulates scallop muscle by changing myosin flexibility.
AB  - Muscle myosins are molecular motors that convert the chemical free energy
      available from ATP hydrolysis into mechanical displacement of actin filaments,
      bringing about muscle contraction. Myosin cross-bridges exert force on actin
      filaments during a cycle of attached and detached states that are coupled to each
      round of ATP hydrolysis. Contraction and ATPase activity of the striated adductor
      muscle of scallop is controlled by calcium ion binding to myosin. This mechanism
      of the so-called "thick filament regulation" is quite different to vertebrate
      striated muscle which is switched on and off via "thin filament regulation"
      whereby calcium ions bind to regulatory proteins associated with the actin
      filaments. We have used an optically based single molecule technique to measure
      the angular disposition adopted by the two myosin heads whilst bound to actin in
      the presence and absence of calcium ions. This has allowed us to directly observe
      the movement of individual myosin heads in aqueous solution at room temperature
      in real time. We address the issue of how scallop striated muscle myosin might be
      regulated by calcium and have interpreted our results in terms of the structures
      of smooth muscle myosin that also exhibit thick filament regulation.

PMID- 16404593
TI  - Chronic pelvic pain syndrome/chronic prostatitis affect the acrosome reaction in
      human spermatozoa.
AB  - Male genital tract inflammations constitute an important factor of male
      subfertility in which different mediators are discussed damaging sperm membranes.
      As acrosome reaction (AR) is ultimately a membrane function, this study aimed at
      investigating the effects of the chronic pelvic pain syndrome on AR. In a total
      of 56 patients with chronic pelvic pain syndrome NIH IIIA and NIH IIIB, AR,
      concentration of leucocytes in ejaculate and urine after prostate massage, sperm
      concentration, motility, vitality and morphology were determined. The control
      group (n = 95) consisted of patients with normozoospermia and proven absence of
      signs of inflammation. Compared to the control, both patients groups showed
      poorer sperm morphology (P < 0.0001) and sperm concentration (P < 0.002). In
      addition, while maximum AR was not affected, inducibility of AR was significantly
      lower (P < 0.004) and spontaneous AR increased (P < 0.02). Our data clearly
      demonstrate a significant influence of the inflammation on acrosomal
      functionality, which could be mediated by inflammatory mediators like ROS.

PMID- 16404594
TI  - [Surgical procedures for severely obese patients: impact and long-term results].
AB  - Obesity is a multifactorial, genetically-determined, neuroendocrine, and chronic
      condition. Conservative treatment of patients with class II and III obesity (BMI
      >35 kg/m(2)) has only modest long-term success. Surgical procedures have been
      used since 1954, and the methods used are continually being updated and improved.
      With experienced surgeons, patients can achieve a weight reduction from around
      50% with purely restrictive procedures, increasing to 75% with combined
      restrictive-malabsorptive methods. All weight-loss methods offer a considerable
      improvement or elimination of obesity-related co-morbidities and substantially
      improvement of quality of life. Well-documented, long-term studies reveal a
      perioperative mortality of 0.2-1.0%, dependent on the surgeon's experience, and a
      maximum perioperative morbidity of 20%. Bariatric surgery is accepted as evidence
      based, safe and effective treatment of obesity.

PMID- 16404596
TI  - PET imaging of brain astrocytoma with 1-11C-acetate.
AB  - PURPOSE: The purpose of this study was to assess the use of 1-(11)C-acetate (ACE)
      as a metabolic tracer for the detection and characterisation of astrocytomas.
      METHODS: Positron emission tomography (PET) studies with ACE and 2-(18)F-fluoro-2
      deoxy-D-glucose (FDG) were performed sequentially in 26 patients with primary
      astrocytomas. Images were analysed by visual interpretation and determination of
      the tumour to cortex ratio (T/C ratio) and standardised uptake value (SUV). The
      tumour uptake was visually scored into three grades as compared with the
      contralateral cortex: clearly lower (-), almost equal (+) and clearly higher
      (++). RESULTS: There were 85% of astrocytomas with ++ ACE uptake, 15% with + ACE
      uptake and none with - ACE uptake. Only 19% of astrocytomas had ++ FDG uptake.
      Thirty-seven percent of high-grade astrocytomas had + FDG uptake and 37% had -
      FDG uptake. The sensitivity and specificity of the FDG T/C ratio in
      discriminating high-grade from low-grade astrocytomas were 79% and 100%,
      respectively, at the cutoff value of 0.75. Using 2.33 as the cutoff value of the
      ACE T/C ratio, the sensitivity and specificity were 42% and 86%, respectively.
      FDG was better than ACE in discriminating high-grade from low-grade astrocytomas.
      T/C ratios and SUVs of FDG uptake of tumours correlated with the histological
      grades, but those of ACE uptake did not. CONCLUSION: ACE appears to be a
      promising tracer for use in the detection of primary astrocytomas, but is of
      limited value in the differentiation of high- and low-grade astrocytomas. ACE is
      complementary to FDG for the diagnosis and characterisation of astrocytoma.

PMID- 16404595
TI  - Prognostic relevance of FDG PET in patients with neurofibromatosis type-1 and
      malignant peripheral nerve sheath tumours.
AB  - PURPOSE: In patients with neurofibromatosis type-1 (NF1) and malignant peripheral
      nerve sheath tumours (MPNSTs), survival rates are low and time to death is often
      less than 2 years. However, there are patients with a more favourable prognosis
      who develop metastases rather late or not at all. Since histopathology and tumour
      grading are not well correlated with prognosis, we aimed to evaluate the
      potential of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for
      prediction of patient outcome in MPNST. METHODS: FDG PET was performed in 16
      patients with NF1 and MPNSTs. Standardised uptake values (SUVs) were calculated
      for each tumour and correlated to tumour grade and patient outcome in terms of
      survival or death. RESULTS: Three patients with tumour grade II had an SUV <3.
      None of these patients developed metastases or died during a follow-up of 41-62
      months. Thirteen patients with tumour grades II and III had an SUV >3. Only one
      of these patients is still alive after 20 months; the remaining 12 died within 4
      33 months. SUV predicted long-term survival with an accuracy of 94%, compared
      with 69% for tumour grade. In Kaplan-Meier survival analysis, patients with an
      SUV >3 had a significantly shorter mean survival time, 13 months, than patients
      with an SUV <3, in whom the mean survival time was 52 months. Tumour grading did
      not reveal differences in survival time (15 vs 12 months). CONCLUSION: Tumour SUV
      obtained by FDG PET was a significant parameter for prediction of survival in NF1
      patients with MPNSTs while histopathological tumour grading did not predict
      outcome.

PMID- 16404598
TI  - Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to
      radiation therapy in murine SCCVII tumors.
AB  - PURPOSE: 3'-Deoxy-3'-[(18)F]fluorothymidine (FLT) is a promising new
      radiopharmaceutical for imaging cell proliferation. We evaluated whether FLT PET
      can be used to monitor early responses to radiation treatment. METHODS: C3H/HeN
      mice bearing murine squamous cell carcinomas were randomized to irradiation with
      0, 10, or 20 Gy. Twenty-four hours later, the mice were sacrificed for
      histopathological and biological assessment such as cell cycle analysis, Hoechst
      staining, and clonogenic cell survival assay. PET scans were performed on other
      mice after injection of [(18)F]FLT or [(18)F]fluorodeoxyglucose (FDG) before and
      after radiation treatment, and tumor growth was assessed over 9 days. RESULTS:
      Histopathological examination detected no morphological changes 24 h after
      radiation treatment, but cell cycle analysis showed that irradiated tumors had a
      decreased fraction of cells in S phase and an increased fraction in G2-M phase,
      compared with nonirradiated tumors. Irradiated tumors also had a higher incidence
      of apoptotic features and reduced clonogenic cell survival. Tumor growth was
      significantly delayed in irradiated mice (p<0.001) compared with control mice.
      PET images showed increased tumoral uptake of both FLT and FDG before radiation
      treatment. Following irradiation, FLT uptake differed significantly (p=0.020)
      from that in control mice. In contrast, FDG uptake after irradiation did not
      differ significantly from that in control mice. CONCLUSION: Our finding that
      tumor uptake of FLT was reduced at 24 h after radiation treatment suggests that
      FLT PET may be a promising imaging modality for monitoring the early effects of
      radiation therapy.

PMID- 16404597
TI  - Role of pre-operative imaging using 99mTc-MIBI and neck ultrasound in patients
      with secondary hyperparathyroidism who are candidates for subtotal
      parathyroidectomy.
AB  - PURPOSE: The purpose of this study was to assess whether pre-operative (99m)Tc
      methoxyisobutylisonitrile (MIBI) scintigraphy and neck ultrasound (US) are of
      value in improving the outcome of subtotal parathyroidectomy in patients with
      secondary hyperparathyroidism. METHODS: Forty-eight consecutive haemodialysis
      patients with severe secondary hyperparathyroidism prospectively underwent
      "blinded" subtotal parathyroid surgery, with 1-year follow-up to establish cure
      or relapse of their secondary hyperparathyroidism. Double-phase (99m)Tc-MIBI
      scintigraphy and neck US were performed pre-operatively in all patients. When the
      preserved gland showed (99m)Tc-MIBI uptake or an abnormal size on US, it was
      considered that "(99m)Tc-MIBI advice" and "US advice", respectively, had not been
      followed. Pre-operative and follow-up parathyroid hormone (PTH) levels were
      obtained in all patients. All data were evaluated on a patient by patient basis.
      RESULTS: Four parathyroid glands were identified in each patient at primary
      surgery, resulting in an operative success rate of 100%. Their weight ranged from
      15 to 7,300 mg (mean 1,120+/-900 mg). Nine of the 48 patients (19%) showed a
      recurrence of their secondary hyperparathyroidism. The recurrence rate was 2%
      (1/48) and 10% (5/48), respectively, when (99m)Tc-MIBI and US advice was
      followed. The sensitivity, specificity, NPV and PPV for pre-operative imaging
      were 72%, 95%, 97% and 80% respectively for (99m)Tc-MIBI, and 55%, 67%, 87% and
      28% for US. CONCLUSION: (99m)Tc-MIBI scintigraphy is a reliable non-invasive
      exploratory tool and its preoperative use results in a significant reduction in
      the number of recurrences in haemodialysis patients with secondary
      hyperparathyroidism who are candidates for subtotal parathyroidectomy. The use of
      neck US did not significantly improve the results obtained with (99m)Tc-MIBI
      alone.

PMID- 16404599
TI  - Oligonucleotide-directed gene repair in wheat using a transient plasmid gene
      repair assay system.
AB  - Oligonucleotide-directed gene repair is a potential technique for agricultural
      trait modification in economically important crops. However, large variation in
      the repair frequencies among the scientific reports indicates that there are many
      factors influencing the repair process. We report here a transient assay system
      using GFP as a reporter for testing the efficiency of plasmid DNA repair in
      cultured wheat cells. This assay showed that osmotic medium supplemented with 2,4
      D increased the oligo-targeting frequency, and that the repair of a point
      mutation was more efficient than repair of a single base deletion mutation in
      cultured scutellum cells of immature wheat embryos. This study provides the first
      evidence that oligonucleotide-directed mutagenesis is applicable to regenerable
      cultured wheat scutellum cells.

PMID- 16404600
TI  - Transformation of Actinidia eriantha: a potential species for functional genomics
      studies in Actinidia.
AB  - Protocols were developed for regeneration and Agrobacterium-mediated
      transformation of Actinidia eriantha Benth. A. eriantha has a number of features
      that make it a useful tool for functional genomics in Actinidia: the vines are
      relatively small and non-vigorous in nature, flowers form all over the vine
      including on lower axillary branches and the species flowers prolifically in
      greenhouse conditions. Flowering and fruiting of transgenic A. eriantha plants
      was obtained within 2 years of transformation in a containment greenhouse. GUS
      (beta-glucuronidase) activity indicating stable expression of the uidA gene was
      observed in leaf, stem, root, petal and fruit tissues. Molecular evidence for
      incorporation of transgenes into the A. eriantha genome was obtained by PCR and
      DNA gel blot analysis. Inheritance of transgenic phenotypes was demonstrated in
      seedling progeny. Functional genomic studies in kiwifruit have been initiated
      using transgenic A. eriantha plants.

PMID- 16404601
TI  - A novel isoform of ATPase c subunit from pearl millet that is differentially
      regulated in response to salinity and calcium.
AB  - Vacuolar ATPases help in maintaining the pH of the vacuoles and thereby play a
      crucial role in the functioning of vacuolar sodium-proton antiporter. Though the
      various subunits that make V(1) and V(0) sector have been reported in plants
      their regulation is not understood completely. We have cloned three different
      isoforms of vacuolar ATPase subunit c (VHA-c) from Pennisetum glaucum with
      homologies among themselves varying from 38% to approximately 73% at the nucleic
      acid level. Using real-time PCR approach we have shown that the three isoforms
      are regulated in a tissue-specific manner under salinity stress. While isoform
      III is constitutively expressed in roots and shoots and does not respond to
      stress, isoform I is upregulated under stress. Isoform II is expressed mainly in
      roots; however, under salinity stress its expression is downregulated in roots
      and upregulated in shoots. Tissue specific expression under salinity stress of
      isoform II was also seen after exogenous application of calcium. This study for
      the first time shows the presence of three isoforms of PgVHA-c and their
      differential regulation during plant development, and also under abiotic stress.

PMID- 16404602
TI  - Spatial contrast sensitivity of birds.
AB  - Contrast sensitivity (CS) is the ability of the observer to discriminate between
      adjacent stimuli on the basis of their differences in relative luminosity
      (contrast) rather than their absolute luminances. In previous studies, using a
      narrow range of species, birds have been reported to have low contrast detection
      thresholds relative to mammals and fishes. This was an unexpected finding because
      birds had been traditionally reported to have excellent visual acuity and color
      vision. This study reports CS in six species of birds that represent a range of
      visual adaptations to varying environments. The species studied were American
      kestrels (Falco sparverius), barn owls (Tyto alba), Japanese quail (Coturnix
      coturnix japonica), white Carneaux pigeons (Columba livia), starlings (Sturnus
      vulgaris), and red-bellied woodpeckers (Melanerpes carolinus). Contrast
      sensitivity functions (CSFs) were obtained from these birds using the pattern
      electroretinogram and compared with CSFs from the literature when possible. All
      of these species exhibited low CS relative to humans and most mammals, which
      suggests that low CS is a general characteristic of birds. Their low maximum CS
      may represent a trade-off of contrast detection for some other ecologically vital
      capacity such as UV detection or other aspects of their unique color vision.

PMID- 16404603
TI  - Bumblebees directly perceive variations in the spectral quality of illumination.
AB  - Individual bumblebees were tested on a task of walking along a test tunnel to
      collect sucrose solution in an initial training illumination condition that
      simulated natural daylight, and in two spectrally different illumination
      conditions. Compared to the training condition the bees took a significantly
      longer time to complete the task in conditions that simulated either an
      ultraviolet negative illumination environment, or an illumination environment
      that represented blue skylight. In a control condition, bees did not derive this
      cue from spectral information reflected from the dark background material. This
      result shows that bees can directly perceive spectral changes in illumination
      conditions, even in the context of a task that does not require colour
      processing. This potentially enables the visual system of bees to have prior
      knowledge about the spectral quality of illumination conditions in which they may
      forage. The findings are discussed in relation to both theoretical models and
      empirical evidence of colour constancy, and it is concluded that bees can use
      multiple mechanisms to solve the dilemma posed by having to find colour targets
      in the spectrally different illumination conditions that exist for insects
      visiting flowers.

PMID- 16404604
TI  - Effects of electrical stimulation of the medullary raphe nuclei on respiratory
      movement in rats.
AB  - The present study was undertaken to examine the effects of electrical stimulation
      of the medullary raphe nuclei on respiration in rats anesthetized with ketamine
      and xylazine. Train pulse stimuli (100 Hz, 10-30 microA) were applied in the
      regions of the caudal raphe nuclei: the raphe magnus (RM), raphe pallidus (RP)
      and raphe obscurus (RO). Stimulation of the RM depressed inspiratory movements
      measured by means of an abdominal pneumograph, whereas stimulation of the RP
      augmented inspiratory movements. It was revealed that stimulation of the RO
      induced either inhibitory or facilitatory effects on respiratory movements
      depending on the stimulation sites. These findings confirm and extend previous
      studies concerning the effects of raphe stimulation on respiratory activity in
      cats. The present results demonstrate that in rats the caudal raphe nuclei are
      involved in respiratory control.

PMID- 16404605
TI  - Diversity in sound pressure levels and estimated active space of resident killer
      whale vocalizations.
AB  - Signal source intensity and detection range, which integrates source intensity
      with propagation loss, background noise and receiver hearing abilities, are
      important characteristics of communication signals. Apparent source levels were
      calculated for 819 pulsed calls and 24 whistles produced by free-ranging resident
      killer whales by triangulating the angles-of-arrival of sounds on two beamforming
      arrays towed in series. Levels in the 1-20 kHz band ranged from 131 to 168 dB re
      1 microPa at 1 m, with differences in the means of different sound classes
      (whistles: 140.2+/-4.1 dB; variable calls: 146.6+/-6.6 dB; stereotyped calls:
      152.6+/-5.9 dB), and among stereotyped call types. Repertoire diversity carried
      through to estimates of active space, with "long-range" stereotyped calls all
      containing overlapping, independently-modulated high-frequency components (mean
      estimated active space of 10-16 km in sea state zero) and "short-range" sounds (5
      9 km) included all stereotyped calls without a high-frequency component,
      whistles, and variable calls. Short-range sounds are reported to be more common
      during social and resting behaviors, while long-range stereotyped calls
      predominate in dispersed travel and foraging behaviors. These results suggest
      that variability in sound pressure levels may reflect diverse social and
      ecological functions of the acoustic repertoire of killer whales.

PMID- 16404606
TI  - Fatal outcome of herpes simplex virus type 1-induced necrotic hepatitis in a
      neonate.
AB  - In neonates, herpes simplex virus (HSV) infections can lead to severe diseases
      associated with high mortality. We report a 6-day-old girl who developed clinical
      signs of fulminant hepatic failure accompanied by infectious-toxic shock and
      disseminated coagulopathy secondary to HSV type 1 (HSV-1) infection. The
      diagnosis was performed postmortem by demonstration of HSV-1 DNA in liver tissue
      as well as by retrospective detection of HSV-specific antibodies.

PMID- 16404607
TI  - Prevalence and pattern of drug resistance mutations among antiretroviral-treated
      HIV-1 patients with suboptimal virological response in Malaysia.
AB  - To assess the prevalence of major drug resistance mutations in antiretroviral
      (ARV)-treated patients with detectable viral load (VL) in Kuala Lumpur, Malaysia,
      genotypic resistance testing was performed among treated human immunodeficiency
      virus type 1 (HIV-1) patients attending the University Malaya Medical Center
      between July 2003 and November 2004. The reverse transcriptase (RT) and protease
      genes from 36 plasma samples with detectable VL were examined for major mutations
      associated with ARV resistance as reported by the International AIDS Society-USA
      Drug Resistance Mutations Group. The prevalence of patients with at least one
      major mutation conferring drug resistance to nucleoside RT inhibitors (NRTIs),
      non-NRTIs (NNRTIs) or protease inhibitors (PIs) was 77.8%. In the RT gene, the
      frequency of mutations associated with NRTIs and NNRTIs resistance was 52.8 and
      63.9%, respectively, with M184V and K103N mutations being selected most
      frequently by these drugs. A patient with Q151M mutation complex was also
      detected. Twenty-two percent of the patients had mutations associated with PIs.
      The following pattern of prevalence of ARV-resistant HIV-1 variants was observed:
      NNRTI-resistant > NRTI-resistant > PI-resistant. The prevalence of major drug
      resistance mutations among ARV-treated patients with detectable VL is high in
      Kuala Lumpur. Genotypic drug resistance testing is therefore important for
      monitoring patients experiencing ARV regimen failure.

PMID- 16404608
TI  - Resistin as a putative modulator of insulin action in the daily feeding/fasting
      rhythm.
AB  - Resistin and adiponectin are adipokines with postulated opposite functions.
      Resistin has been related with insulin resistance in obesity, while adiponectin
      could be associated to higher insulin sensitivity. We have determined whether the
      production of these two adipokines during the day is related to the feeding
      rhythm in rats. Resistin mRNA levels in adipose tissue correlated positively with
      the gastric contents and serum insulin concentration, showing higher levels
      during the dark phase (period of the highest food intake), especially in the
      mesenteric depot, while levels decreased during the light phase. The diurnal
      pattern of resistin expression was not directly reflected in the circulating
      levels, but it showed a 6-h delay and correlated negatively with the gastric
      contents and serum insulin. Adiponectin expression followed an opposite pattern,
      not apparently related to feeding or insulin release, and not translated into
      changes in circulating levels. Moreover, considering that insulin stimulates
      resistin expression and that circulating resistin follows a contrary circadian
      pattern in comparison to insulin, resistin, apart from its role in the increased
      insulin resistance associated to obesity, could also act as a putative modulator
      of insulin in the daily feeding/fasting rhythm through a negative feedback
      regulation of its action.

PMID- 16404610
TI  - Effect of repetitive stimulation on cell volume and its relationship to membrane
      potential in amphibian skeletal muscle.
AB  - The effect of electrical stimulation on cell volume, V (c), and its relationship
      to membrane potential, E (m), was investigated in Rana temporaria striated
      muscle. Confocal microscope xz-plane scanning and histology of plastic sections
      independently demonstrated significant and reversible increases in V (c) of
      19.8+/-0.62% (n=3) and 27.1+/-8.62% (n=3), respectively, after a standard
      stimulation protocol. Microelectrode measurements demonstrated an accompanying
      membrane potential change, DeltaE (m), of +23.6+/-0.98 mV (n=3). The extent to
      which this DeltaE (m) might contribute to the observed changes in V (c) was
      explored in quiescent muscle exposed to variations in extracellular potassium
      concentration, [K(+)](e). E (m) and V (c) varied linearly with log [K(+)](e) and
      [K(+)](e), respectively, in the range 2.5-15 mM (R (2)=0.99 and 0.96), and these
      results were used to reconstruct an approximately linear relationship between V
      (c) and E (m) (DeltaV (c)=0.85E (m)+68.53; R (2)=0.99) and hence derive the
      DeltaV (c) expected from the DeltaE (m) during stimulation. This demonstrated
      that both the time course and magnitude of the increase and recovery of V (c)
      observed in active muscles could be reproduced by the corresponding [K(+)](e)
      induced depolarisation in quiescent muscles, suggesting that the depolarisation
      associated with membrane activity makes a substantial contribution to the cell
      swelling during exercise. Furthermore, conditions of Cl(-) deprivation abolished
      the relationship between E (m) and V (c), supporting a mechanism in which the
      depolarisation of E (m) drives a passive redistribution of Cl(-) and hence
      cellular entry of Cl(-) and K(+) and an accompanying, osmotically driven,
      increase in V (c).

PMID- 16404611
TI  - Sensory feedback mechanism underlying entrainment of central pattern generator to
      mechanical resonance.
AB  - Rhythmic body motions observed in animal locomotion are known to be controlled by
      neuronal circuits called central pattern generators (CPGs). It appears that CPGs
      are energy efficient controllers that cooperate with biomechanical and
      environmental constraints through sensory feedback. In particular, the CPGs tend
      to induce rhythmic motion of the body at a natural frequency, i.e., the CPGs are
      entrained to a mechanical resonance by sensory feedback. The objective of this
      paper is to uncover the mechanism of entrainment resulting from the dynamic
      interaction of the CPG and mechanical system. We first develop multiple CPG
      models for the reciprocal inhibition oscillator (RIO) and examine through
      numerical experiments whether they can be entrained to a simple pendulum. This
      comparative study identifies the neuronal properties essential for the
      entrainment. We then analyze the simplest model that captures the essential
      dynamics via the method of harmonic balance. It is shown that robust entrainment
      results from a strong, positive-feedback coupling of a lightly damped mechanical
      system and the RIO consisting of neurons with the complete adaptation property.

PMID- 16404609
TI  - Effect of adenovirus-mediated gene transfer of nitric oxide synthase on vascular
      reactivity of rat isolated pulmonary arteries.
AB  - Aerosol gene transfer of endothelial nitric oxide synthase (eNOS) and inducible
      NOS (iNOS) to rat lungs increased NOS expression and activity, and prevented
      hypoxic pulmonary vasoconstriction (HPV) in vivo. Hereby, we examined the effect
      of eNOS and iNOS aerosol gene transfer on the endothelium-dependent relaxation
      (EDR) and on acute HPV in isolated rat pulmonary arteries. Changes in isometric
      forces were recorded in organ baths for large conduit arteries (diameter 1.8+/
      0.1 mm) and in a wire myograph for small resistance arteries (258+/-35 microm).
      Male Wistar rats were randomly aerosolized with adenovirus (Ad) encoding beta
      galactosidase (control), eNOS, or iNOS. Four days later, exhaled nitric oxide was
      measured, NOS expression within rat lungs was evaluated by quantitative real-time
      polymerase chain reaction and immunohistochemistry, vasoconstricting agonist and
      acetylcholine concentration response curves were generated, and the time course
      of HPV was recorded. Human eNOS and murine iNOS were expressed within rat lung
      tissue mostly in parenchyma and endothelial cells. Large arteries isolated from
      Ad-i, eNOS-aerosolized rats developed lower agonist-induced tension than those of
      control rats. The first and second contractions of the HPV were smaller in the Ad
      i, eNOS-aerosolized rats. Contractions were modestly, but significantly and
      inversely, related to exhaled NO. Agonist- and hypoxia-induced contractions were
      even more reduced after eNOS aerosolization. There was no significant effect on
      EDR and no notable difference between small and large vessels. We conclude that
      adenovirus (Ad)-mediated NOS gene transfer can counteract both pharmacologically
      and hypoxia-induced increases in pulmonary vascular tone in isolated rat
      pulmonary arteries. eNOS seems as efficient as iNOS in regulating pulmonary
      vascular tone.

PMID- 16404612
TI  - A binocular pupil model for simulation of relative afferent pupil defects and the
      swinging flashlight test.
AB  - Many important intracranial neural pathways are involved in the control of the
      two muscles of the human pupil and the observation and analysis of pupil
      responses to light or other stimuli is of great interest in many clinical
      procedures. The binocular pupil model presented in this document has a topology
      encompassing much of the complexity of the pupil system neurophysiology. The
      dynamic parameters of the model were matched against pupil experiments under
      multiple conditions. It is employed here to simulate responses to the swinging
      flashlight test, a procedure which is routinely practiced in ophthalmology to
      diagnose different degrees of relative afferent pupil defects often a consequence
      of severe optic nerve diseases or retinal dysfunctions. Other, not light
      dependent, pupil stimuli are briefly discussed.

PMID- 16404613
TI  - BMI, pain and hyper-mobility are determinants of long-term outcome for women with
      low back pain and pelvic pain during pregnancy.
AB  - Low back pain and pelvic pain (LBPP) is common during pregnancy and up to 40% of
      women still have symptoms half a year after delivery. The aim of the study was to
      investigate determinants and the prevalence of persistent LBPP after pregnancy in
      a Swedish cohort. In a previous study 891 women had responded to a questionnaire
      on risk factors and prevalence of LBPP during pregnancy. Altogether 72% (n=639)
      of the women had reported LBPP during pregnancy. These respondents were sent a
      second questionnaire at approximately 6 months after delivery. The response rate
      was 72.6% (n=464). Independent t-test and Pearson's chi-squared test were used to
      test the difference between the two groups. In response to the questionnaire,
      43.1% of the women reported persistent LBPP 6 months after delivery. Women with
      persistent LBPP after pregnancy had had significantly earlier onset of pain
      during pregnancy, higher maternal age, higher body mass index (BMI), and assessed
      a higher level of pain due to LBPP during pregnancy and after pregnancy, and
      included a higher proportion of women with joint hyper-mobility. In summary,
      recurrent or continuous LBPP is prevalent after pregnancy. BMI as well as hyper
      mobility are prominent determinants of persistent LBPP after pregnancy. Level and
      onset of pain during pregnancy were strong predictors of persistent LBPP.

PMID- 16404614
TI  - Prediction of polyamide properties using quantum-chemical methods and BP
      artificial neural networks.
AB  - Quantitative structure -property relationships (QSPR) for glass translation
      temperatures (T (g)), density (rho) and indices of refraction (n) of the
      polyamides have been determined. All descriptors are calculated from molecular
      structures at the B3LYP/6-31G(d) level. These QSPR models are generated by two
      methods: multiple linear regression (MLR) and error back-propagation artificial
      neural networks (BPANN). The model obtained by MLR is used for the calculations
      of T (g) (R (training)=0.9074, SD(training)=22.4687, R (test)=0.8898,
      SD(test)=23.2417), rho (R (training)=0.9474, SD(training)=0.0422, R
      (test)=0.8928, SD (test)=0.0422), n (R (training)=0.9298, SD(training)=0.0204, R
      (test)=0.9095, SD(test)=0.0274). The model obtained by BPANN is used for the
      calculations of T (g) (R (training)=0.9273, SD(training)=14.8988, R
      (test)=0.8989, SD(test)=16.4396), rho (R (training)=0.9523, SD(training)=0.0466,
      R (test)=0.9014, SD(test)=0.0512), n (R (training)=0.9401, SD(training)=0.0131, R
      (test)=0.9445, SD(test)=0.0179). These results demonstrate that the MLR and BPANN
      methods can be used to predict T (g), rho and n. The more accurate predicted
      results are obtained from BPANN. Figure: Experimental vs. calculated n with cross
      validation method (BPANN) for the training set of 53 polyamides and the test set
      of 14 polyamides. Figure Experimental vs. calculated n with cross-validation
      method (BPANN) for the training set of 53 polyamides and the test set of 14
      polyamides. [Figure: see text].

PMID- 16404615
TI  - Reparameterized Austin Model 1 for quantitative structure-property relationships
      in liquid media.
AB  - A reparameterization of the quantum-chemical AM1 (Austin Model 1) model has been
      carried out using a nonlinear optimization based on a modification of the
      Levenberg-Marquardt technique. The optimum numerical values for the one-electron
      resonance integral parameters (beta (s) and beta (p)) and core-core repulsion
      atomic parameters alpha were obtained for the elements H, C, N, O, Cl and Br
      using the statistical fit of a two-parameter QSPR equation for the boiling points
      of organic compounds. A substantially improved two-parameter correlation
      (R2=0.9685, s=13.48 K) was obtained by using the new optimized parameters. The
      QSPR equation employs two molecular descriptors, a bulk cohesiveness descriptor,
      [Formula: see text] and the area-weighted surface charge of hydrogen-bonding
      donor atom(s) in the molecule. The model developed shows remarkably accurate
      predictions of the normal boiling points for nine additional simple inorganic
      compounds. The new parameters were tested on the critical temperatures of 165
      organic compounds. The new QSPR model obtained for this property was found to be
      statistically significantly better than the original model. [Figure: see text].

PMID- 16404616
TI  - Study on improving the selectivity of compounds that inhibit two PI3Ks (gamma and
      delta).
AB  - A desirable characteristic of PI3K inhibitors is their selectivity. Up to now,
      there has been no report that describes the 3 D-structure differences between two
      PI3Ks (delta and gamma) and applies them to designing selective compounds. In the
      present study, we used an approach combining protein-structure modeling, GRID/PCA
      (Principal Component Analysis) and docking methods to investigate the detail
      interactions of the two PI3Ks with various chemical groups. At first, we
      constructed a 3 D-model of the PI3Kdelta catalytic subunit with the program
      Modeller7.0 based on the high resolution X-ray structure of the PI3Kgamma
      catalytic subunit, and then employed GRID and PCA to reveal the most relevant
      structural and physicochemical differences between the two PI3Ks related to their
      selectivity. As a result, the analysis unveiled the most important regions on the
      two PI3Ks that should be taken into account for the design of selective
      inhibitors. Finally, based on activity data of 10 PI3Kdelta-selective compounds,
      a docking study validated the results of the GRID/PCA method, which suggested
      that the approach could provide clear guidelines for selective drug design.

PMID- 16404617
TI  - Investigation of the binding mode of (-)-meptazinol and bis-meptazinol
      derivatives on acetylcholinesterase using a molecular docking method.
AB  - Molecular docking has been performed to investigate the binding mode of (-)
      meptazinol (MEP) with acetylcholinesterase (AChE) and to screen bis-meptazinol
      (bis-MEP) derivatives for preferable synthetic candidates virtually. A reliable
      and practical docking method for investigation of AChE ligands was established by
      the comparison of two widely used docking programs, FlexX and GOLD. In our hands,
      we had more luck using GOLD than FlexX in reproducing the experimental poses of
      known ligands (RMSD<1.5 A). GOLD fitness values of known ligands were also in
      good agreement with their activities. In the present GOLD docking protocol, (-)
      MEP seemed to bind with the enzyme catalytic site in an open-gate conformation
      through strong hydrophobic interactions and a hydrogen bond. Virtual screening of
      a potential candidate compound library suggested that the most promising 15 bis
      MEP derivatives on the list were mainly derived from (-)-MEP with conformations
      of (S,S) and (SR,RS) and with a 2- to 7-carbon linkage. Although there are still
      no biological results to confirm the predictive power of this method, the current
      study could provide an alternate tool for structural optimization of (-)-MEP as
      new AChE inhibitors. [Figure: see text].

PMID- 16404619
TI  - A taxonomy of health utility assessment methods and the role for uncertainty
      analysis.

PMID- 16404620
TI  - Comparing costs and effectiveness of different starting points for highly active
      antiretroviral therapy in HIV-positive patients. Evidence from the ICONA cohort.
AB  - We evaluated the costs and effectiveness of starting highly active antiretroviral
      therapy (HAART) at different points during the course of HIV infection, defined
      on the basis of CD4 T-lymphocytes counts. The study considered 3,250 HAART-naive
      patients of the Italian Cohort Naive Antiretrovirals (ICONA), enrolled and
      followed between 1997 and 2002. In correspondence to the thresholds of 500, 350,
      and 200 CD4 cells/mm(3), we selected immediate and deferred groups accounting for
      lead-time bias. The effects of immediate vs. deferred treatment on AIDS-free
      survival and direct health costs were estimated stratifying on the propensity
      score of immediate HAART initiation. The incremental cost-effectiveness ratio
      (ICER) and the cost-effectiveness acceptability curve were also obtained.
      Although immediate HAART initiation did not affect incidence AIDS and death at
      high CD4 levels, starting HAART with 200-349 CD4 cells/mm(3) rather than
      deferring it below 200 CD4 cells/mm(3), proved to be cost-effective.

PMID- 16404618
TI  - Model of the whole rat AT1 receptor and the ligand-binding site.
AB  - We present a three-dimensional model of the rat type 1 receptor (AT1) for the
      hormone angiotensin II (Ang II). Ang II and the AT1 receptor play a critical role
      in the cell-signaling process responsible for the actions of renin-angiotensin
      system in the regulation of blood pressure, water-electrolyte homeostasis and
      cell growth. Development of improved therapeutics would be significantly enhanced
      with the availability of a 3D-structure model for the AT1 receptor and of the
      binding site for agonists and antagonists. This model was constructed using a
      combination of computation and homology-modeling techniques starting with the
      experimentally determined three-dimensional structure of bovine rhodopsin
      (PDB#1F88) as a template. All 359 residues and two disulfide bonds in the rat AT1
      receptor have been accounted for in this model. Ramachandran-map analysis and a 1
      nanosecond molecular dynamics simulation of the solvated receptor with and
      without the bound ligand, Ang II, lend credence to the validity of the model.
      Docking calculations were performed with the agonist, Ang II and the
      antihypertensive antagonist, losartan. [Figure: see text].

PMID- 16404621
TI  - Impact of dietary habits on stone incidence.
AB  - Changes in dietary habits and lifestyle are suggested to contribute markedly to
      the rise in the prevalence and incidence of urolithiasis during the past decades.
      Insufficient fluid intake and diets rich in animal protein are considered to be
      important determinants of stone formation. Overweight and associated dietary
      pattern additionally contribute to the increasing incidence and prevalence of
      stone disease. Reduction of overweight through extreme fasting or high-protein
      weight-loss diets, e.g. Atkins diet, also appear to affect stone formation.
      Although there is evidence that changes in dietary habits can reduce urinary risk
      factors and the risk of stone formation, further randomized controlled clinical
      trials are necessary to evaluate long-term effects of dietary interventions on
      stone disease.

PMID- 16404623
TI  - The INFVo perceptual rating scale for substitution voicing: development and
      reliability.
AB  - In this paper, an experimental study of inter-judge consistency for the different
      dimensions of a recently proposed new scale for the rating of substitution voices
      is presented. The IINFVo rating scale tries to score five parameters, namely
      impression, intelligibility, noise, fluency and voicing. Each parameter is scored
      between 0 (very good substitution voicing) and 10 (very deviant substitution
      voicing) on a visual analogue scale. Inter-judge consistencies were measured
      among semi-professional as well as among professional jury members. The
      consistencies among semi-professionals, expressed as Pearson correlation
      coefficients, ranged from moderate to good (0.57-0.68), whereas those among
      professionals were good to excellent (0.82-0.87) and compared favourably to
      consistency figures published for traditional perceptual evaluation scales such
      as the GRBAS scale for laryngeal dysphonia. Since there is a strong correlation
      between the scores of impression and intelligibility, and since intelligibility
      is hard to score by non-native listeners, we suggest taking the mean of the two
      scores as the "impression" of a modified dimensional INFVo rating scale. Our
      experiments demonstrate that the INFVo rating scale has good potential to become
      a routine perceptual evaluation method in a multidimensional assessment protocol
      for substitution voicing.

PMID- 16404622
TI  - Renal tubular damage/dysfunction: key to the formation of kidney stones.
AB  - Supersaturation is the driving force behind crystal formation in the kidneys. It
      can, however, result only in the formation of crystals which can be harmlessly
      expelled. For stone formation, crystals must form in the kidneys and be retained
      there, which is indeed a rare occurrence. Crystalluria is common while stone
      formation is not. Only pathological changes in the kidneys including renal injury
      and dysfunction can accomplish crystal retention. Lethal epithelial cellular
      injury promotes crystal nucleation, aggregation and retention. Sub-lethal injury
      or dysfunctional cells may produce ineffective crystallization modulators and
      localized areas of supersaturation in the interstitium. The former will affect
      crystallization in the urine while the latter may cause precipitation in the
      interstitium and development of Randall's plaques.

PMID- 16404624
TI  - Improvement of postural control in patients with peripheral vestibulopathy.
AB  - We present here the results of a short-term prospective study on a group of 37
      patients with persistent unsteadiness. The treatment of these patients was
      customized according to the results of the Sensory Organization Test carried out
      using computerized dynamic posturography. A 5-week period of instrumental
      rehabilitation was established involving visual biofeedback-based computerized
      balance intervention that manipulated the individuals' capacities, the goals of
      the tasks and the environmental context. Exercises were performed twice weekly.
      This adaptation of the treatment was based on the hypothesis that it would reduce
      the level of disability and handicap associated with the unsteadiness suffered by
      these patients. Of the patients, 73% improved their status according to the DHI
      results. Furthermore, in the group of patients that showed an improvement in the
      DHI, their SOT composite score increased significantly, their reaction time
      reduced and their sway velocity, endpoint excursion, maximum excursion and
      directional control all increased. However, for those patients who did not
      experience a significant improvement or who recorded an increase in the total DHI
      score, the modifications in the SOT and LOS tests were not significant.

PMID- 16404625
TI  - Chronic appendicitis "syndrome" manifested by an appendicolith and thickened
      appendix presenting as chronic right lower abdominal pain in adults.
AB  - In this short report, we describe a small series of adult patients with chronic
      appendicitis presenting with chronic right lower quadrant abdominal pain. The
      clinical presentation was unusual and atypical for classic appendicitis because
      of the absence of fever, peritoneal tenderness on focused graded compression of
      the abdomen, and leukocytosis. Computed tomography (CT) findings included the
      presence of an appendicolith and appendiceal thickening, without mesenteric
      infiltration, abscess, or collection. In this series, the appendicolith appeared
      to represent a marker rather than an actual cause of appendicitis. Focused CT
      scans with additional lung and bone windows proved optimal in detecting
      appendicoliths, which were not visible on the scout localizer scans, despite
      windowing modifications. Our findings suggest that chronic appendicitis may be a
      phenomenon unique to adults and should be included in the differential diagnosis
      of chronic right lower quadrant pain in patients seen in the emergency room
      setting. Surgery is curative in such patients, although expectant management is
      an alternative when tolerated by the patient.

PMID- 16404627
TI  - Gene-rich and gene-poor chromosomal regions have different locations in the
      interphase nuclei of cold-blooded vertebrates.
AB  - In situ hybridizations of single-copy GC-rich, gene-rich and GC-poor, gene-poor
      chicken DNA allowed us to localize the gene-rich and the gene-poor chromosomal
      regions in interphase nuclei of cold-blooded vertebrates. Our results showed that
      the gene-rich regions from amphibians (Rana esculenta) and reptiles (Podarcis
      sicula) occupy the more internal part of the nuclei, whereas the gene-poor
      regions occupy the periphery. This finding is similar to that previously reported
      in warm-blooded vertebrates, in spite of the lower GC levels of the gene-rich
      regions of cold-blooded vertebrates. This suggests that this similarity extends
      to chromatin structure, which is more open in the gene-rich regions of both
      mammals and birds and more compact in the gene-poor regions. In turn, this may
      explain why the compositional transition undergone by the genome at the emergence
      of homeothermy did not involve the entire ancestral genome but only a small part
      of it, and why it involved both coding and noncoding sequences. Indeed, the GC
      level increased only in that part of the genome that needed a thermodynamic
      stabilization, namely in the more open gene-rich chromatin of the nuclear
      interior, whereas the gene-poor chromatin of the periphery was stabilized by its
      own compact structure.

PMID- 16404628
TI  - Oedema with proteinuria in Gambian children--a descriptive study.
AB  - The clinical syndrome of oedema with proteinuria is an important cause of
      paediatric morbidity in sub-Saharan Africa. The aim of this study was to assess
      its prevalence, clinical presentation and outcome in The Gambia, where the
      syndrome is perceived to be common but has not previously been studied. All
      children admitted with oedema and proteinuria to three hospitals in the Western
      region of The Gambia between January 1995 and June 1998 were identified
      retrospectively. Hospital records were retrieved to assess admission
      characteristics. All traceable children were clinically reviewed, and urinalysis
      was performed between 3 months and 4 years after admission. Two hundred and two
      children who presented with proteinuria and oedema were identified, accounting
      for 1.2% of paediatric hospital admissions in The Gambia. Haematuria on dipstick
      testing was common (76.5%). Of 39 children who were traced, four (10.3%) were
      dead. Eighteen of the remaining 35 (51.4%) had proteinuria at follow up. Older
      age at first presentation was significantly associated with increased long-term
      morbidity. These preliminary data suggest that oedema with proteinuria may be
      common and could cause long-term morbidity and mortality in Gambian children.
      Further studies on its aetiology and treatment are warranted.

PMID- 16404629
TI  - [Deep brain stimulation in the posterior hypothalamus for chronic cluster
      headache. Case report and review of the literature].
AB  - Primary chronic cluster headache (CCH) is a rare but severe pain syndrome and
      pathophysiological explanations are still missing. PET studies revealed
      activation in the hypothalamus and therefore it became a target for therapeutic
      deep brain stimulation (DBS). A case of a 39-year-old woman and a literature
      review are presented. The patient suffered from left-sided primary CCH for 14
      months. The headache was resistant to any pharmacological therapy or treatment
      was limited by major drug side effects. Using a stereotactic approach a
      quadripolar lead was inserted in the left posterior hypothalamus. A test trial
      was performed and attack frequency, intensity, and adverse events were noted.
      Intraoperative test stimulation evoked typical side effects like tachycardia,
      diplopia and panic attacks. During the trial test a marked reduction in frequency
      and intensity of CCH was recorded. After 7 days the stimulation device was
      implanted subcutaneously. DBS with implantation of a lead in the ipsilateral
      inferior posterior hypothalamus is an experimental treatment option and should be
      offered to selected patients in a prospective controlled clinical trial. Data
      concerning the long-term follow-up need to be collected.

PMID- 16404631
TI  - [Sexual dysfunctions from a neuropsychiatric perspective].
AB  - Sexual dysfunctions are widespread and have an enormous effect on quality of
      life. To understand them, it is necessary to look at both somatic and
      psychosocial factors, especially those concerning partnership. Psychiatric and
      neurologic disorders play an important role. Normally, treatment consists of
      qualified sex counseling and, if necessary, intensive sex therapy. Somatic
      treatment options exist as well.

PMID- 16404630
TI  - [Escalating management of progressive neuropathic cancer pain].
AB  - The management of tumor-related pain, particularly that which is neuropathic in
      origin, is both difficult and challenging. According to WHO guidelines, opioids
      are the first-line analgesics in case of severe tumor-related pain syndromes.
      Some patients receiving continuous opioid therapy rapidly require increase of the
      opioid dose. In this case it can be necessary to extend the analgesic regime and
      to either apply interventional procedures or change the opioid or the route of
      administration. The case presented is remarkable regarding the severity and
      persistent nature of the patient's pain despite a variety of commonly employed
      treatments.

PMID- 16404632
TI  - [Hoarding and severe neglect. A case report].
AB  - Severe neglect of the living space due to excessive collection of unusable
      objects and refuse has been named "Vermuellung" (complete congestion with
      garbage) since 1985 in the German literature. The internationally used terms
      'hoarding' or 'Diogenes syndrome' are in fact neither synonyms nor direct
      translations of the term. The condition is a problem mainly in social and
      geriatric psychiatry, yet it is seen also in young subjects without
      psychopathologic features. A frequent cause for the condition is obsessive
      compulsive disorder, but several other disorders are associated with it. A 58
      year-old female patient with severe Vermuellung due to obsessive-compulsive
      disorder is presented.

PMID- 16404633
TI  - [CERAD and NOSGER. Comparing predictive scales for dementia in a Swiss
      gerontopsychiatric patient population].
AB  - BACKGROUND: The Consortium to Establish a Registry for Alzheimer's Disease
      (CERAD) is an established screening instrument for the diagnosis of Alzheimer's
      disease. The Nurses Observation Scale for Geriatric Patients (NOSGER), actually
      developed for rating the frequency of behavioral disturbances, appears suitable
      for dementia screening as well. MATERIAL AND METHOD: In this retrospective study
      we analyze the neuropsychological data of 400 consecutive patients at our
      hospital with several psychiatric diagnoses and cognitive deficits. By means of
      logistic calculation in single and multivariable models, the predictive value of
      CERAD and NOSGER for dementia diagnosis was studied. RESULTS: All CERAD subtests
      were significant single predictors for dementia. The multivariable model with the
      highest prediction for probability of dementia diagnosis contained the subtests
      Verbal Fluency Test, Word List Recall, Constructional Practice Recall, and the
      Mini-Mental State Examination. However, NOSGER could not differentiate between
      demented and nondemented patients. CONCLUSION: In our gerontopsychiatric
      population, CERAD separates demented patients from nondemented ones with high
      predictive potency. The NOSGER does not reveal any predictive value for the
      diagnosis of dementia.

PMID- 16404634
TI  - Cyclosporin A, tacrolimus and sirolimus are potent inhibitors of the human breast
      cancer resistance protein (ABCG2) and reverse resistance to mitoxantrone and
      topotecan.
AB  - PURPOSE: Several studies have demonstrated significant interactions between
      immunosuppressants (e.g., cyclosporin A) and chemotherapeutic drugs that are BCRP
      substrates (e.g., irinotecan), resulting in increased bioavailability and reduced
      clearance of these agents. One possible mechanism underlying this observation is
      that the immunosuppressants modulate the pharmacokinetics of these drugs by
      inhibiting BCRP. Therefore, the aim of this study was to determine whether the
      immunosuppressants cyclosporin A, tacrolimus and sirolimus are inhibitors and/or
      substrates of BCRP. METHODS: First, the effect of the immunosuppressants on BCRP
      efflux activity in BCRP-expressing HEK cells was measured by flow cytometry.
      RESULTS: Cyclosporin A, tacrolimus and sirolimus significantly inhibited BCRP
      mediated efflux of pheophorbide A, mitoxantrone and BODIPY-prazosin. The EC(50)
      values of cyclosporin A, tacrolimus and sirolimus for inhibition of BCRP-mediated
      pheophorbide A efflux were 4.3 +/- 1.9 microM, 3.6 +/- 1.8 microM and 1.9 +/- 0.4
      microM, respectively. Cyclosporin A, tacrolimus and sirolimus also effectively
      reversed resistance of HEK cells to topotecan and mitoxantrone conferred by BCRP.
      When direct efflux of cyclosporin A, tacrolimus and sirolimus was measured, these
      compounds were found not to be transported by BCRP. Consistent with this finding,
      BCRP did not confer resistance to the immunosuppressants in HEK cells.
      CONCLUSION: These results indicate that cyclosporin A, tacrolimus and sirolimus
      are effective inhibitors but not substrates of BCRP. These findings could explain
      the altered pharmacokinetics of BCRP substrate drugs when co-administered with
      the immunosuppressants and suggest that pharmacokinetic modulation by the
      immunosuppressants may improve the therapeutic outcome of these drugs.

PMID- 16404635
TI  - Identification of genes whose expression is associated with cisplatin resistance
      in human ovarian carcinoma cells.
AB  - The goal of this study was to identify genes consistently differentially
      expressed in multiple pairs of isogenic cisplatin (DDP)-sensitive and resistant
      human ovarian carcinoma cell lines using microarray-based expression profiling.
      Expression profiling was carried out on six pairs of ovarian carcinoma cells
      lines growing under identical conditions; each cell expression profile was
      independently replicated six times. No genes were differentially expressed in all
      six pairs of cells or even in even in any five of the six pairs. Eighteen genes
      and 1 EST were upregulated, and four genes and 1 EST were downregulated, in at
      least four cell pairs. Of these, only metallothionein 2A has previously been
      implicated in DDP resistance. Among the genes identified on the basis of six
      replicates, an average of 24.8% would have been missed if only five replicates
      had been performed, and 38.3% would have been missed with only four replicates.
      The genes did not identify a dominant biochemical pathway or ontology category as
      being linked to DDP resistance; however, hierarchical clustering provided
      evidence for two classes DDP-resistant phenotypes within which there are
      additional cell pair-specific alterations. Many of the genes identified in this
      study play important roles in cell surface interactions and trafficking pathways
      not previously linked to DDP resistance. The genes discovered by this extensively
      replicated analysis are candidates for prediction of DDP responsiveness in
      ovarian cancer patients.

PMID- 16404636
TI  - Fixed dose-rate infusion of gemcitabine in combination with cisplatin and UFT in
      advanced carcinoma of the pancreas.
AB  - BACKGROUND: Gemcitabine is currently considered the standard treatment for
      advanced pancreatic cancer (APC). Cisplatin and a fluoropyrimidine have some
      activity in the treatment of this cancer. The aim of this trial is to evaluate
      the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated
      with cisplatin and UFT in patients with APC. PATIENTS AND METHODS: Forty-six
      chemotherapy-naive patients with APC that was either unresectable or metastatic
      were included in this phase II study. All of them had Karnofsky performance
      status > or =50 and unidimensionally measurable disease. Treatment consisted of
      gemcitabine 1,200 mg/m2 given as a 120-min infusion weekly for three consecutive
      weeks, cisplatin 50 mg/m2 on day 1 and oral UFT 400 mg/m2/day (in two to three
      daily doses) on days 1 to 21; cycles of treatment were given every 28 days.
      RESULTS: A total of 208 cycles of chemotherapy were given with a median of 4 per
      patient. Fourteen patients (30%) achieved partial responses (95% CI 19-48%) and
      17 (37%) had stable disease. The median time to progression was 5 months, and the
      median overall survival 9 months. Nineteen patients (49%; 95% CI 32-64%) had a
      clinical benefit response. Grade 3-4 WHO toxicities were as follows: neutropaenia
      in 26 patients (57%), with 5 cases of febrile neutropaenia (11%),
      thrombocytopaenia in 15 (33%), anaemia in six (13%), diarrhoea in 5 (11%),
      asthenia in 2 (4%) and mucositis in 1 (2%). Seven patients required
      hospitalisation for treatment-related complications. CONCLUSION: A fixed dose
      rate infusion of gemcitabine associated with cisplatin and UFT is active in
      patients with APC, though at the cost of considerable toxicity.

PMID- 16404638
TI  - Decreasing urinary PAH metabolites and 7-methylguanine after smoking cessation.
AB  - OBJECTIVE: Humans are exposed to various carcinogens by smoking. Urinary
      metabolites of polycyclic aromatic hydrocarbons (PAH), one of the major
      carcinogens in cigarette smoke, were measured as the environmental carcinogen
      exposure marker for humans. We evaluated urinary exposure markers for smoking
      cessation. METHOD: In this study, we measured cigarette smoke exposure markers,
      such as urinary cotinine, PAH exposure markers, such as urinary 1-hydroxypyrene
      (1-OHP), 2-naphthol (2-NP) and 1-naphthol (1-NP), as well as a methylating
      chemical exposure marker, 7-methylguanine (7-MeG). The before smoking cessation
      levels of these markers, and the after smoking cessation levels were then
      compared. Eighteen subjects participated in this smoking cessation program.
      RESULTS: Levels of all of four markers were found to have decreased by 19-54%
      after smoking cessation. Urinary cotinine, 1-OHP, 2-NP and 7-MeG levels were
      found to have significantly decreased after smoking cessation. There were
      positive correlations between cotinine and three urinary PAH markers and between
      1-OHP, 2-NP and 7-MeG. CONCLUSION: PAH metabolites were better biomarkers of
      smoking cessation than 7-MeG. Analyzing urinary metabolites or urinary DNA
      adducts is suitable for epidemiological studies.

PMID- 16404637
TI  - No consistent risk factor pattern for symptoms related to the sick building
      syndrome: a prospective population based study.
AB  - OBJECTIVES: To examine associations between perceived indoor environment at work
      and the non-specific symptoms that are often referred to as the sick building
      syndrome (SBS), using cross-sectional and prospective analyses for a large cohort
      from the general population. METHODS: The sample comprised 2,164 adults in
      employment, who completed a postal questionnaire in April 2001. Of these 1,402,
      who were still working and living in the same place, completed a second
      questionnaire a year later. The outcome measures were the prevalence of mucous
      membrane symptoms and general symptoms at baseline and the incidence and
      persistence of these symptoms at follow-up. Self-reports of the indoor
      environment from the baseline questionnaire were used as predictors in the
      analyses. RESULTS: Inconsistent results were found between the cross-sectional
      and the longitudinal analyses for the associations between perceived indoor
      environment factors at work and symptoms. Whereas mucous membrane symptoms in the
      cross-sectional analysis were significantly associated with self-reported high
      temperature and dry air, the prospective analyses showed that onset of mucous
      membrane symptoms was associated with the sensation of draught, dry air, and
      noise. Persistent mucous membrane symptoms were associated only with stuffy air.
      General symptoms were associated with self-reported stuffy air and dry air in the
      cross-sectional analysis, while draught was the only predictor of onset of
      general symptoms. We found no predictors in the indoor environment for the
      persistence of general symptoms. CONCLUSIONS: The symptoms that are often
      connected with SBS are very common symptoms in the general population among
      manual workers as well as non-manual workers. Our study gives only limited
      support to the hypothesis of causal relationships between the indoor environment
      and these symptoms. We found no evidence of persistent mucous membrane symptoms
      and general symptoms related to specific factors in the indoor environment.

PMID- 16404639
TI  - Levine-Sekhar grading system for prediction of the extent of resection of cranial
      base meningiomas revisited: study of 124 cases.
AB  - INTRODUCTION: Skull base meningiomas comprise an intricate kingdom in
      neurological surgery. Due to their proximity to critical neurovascular
      structures, these tumours impose a cumbersome burden on the surgeon regarding
      surgical intervention and the clinical outcome. Preoperative prediction of the
      meningioma resectability will help the surgeon seek a rational result from
      surgery. This study tries to re-examine and promote the Levine-Sekhar (LS)
      grading system proposed to predict the resectability of basal meningiomas.
      PATIENTS AND METHODS: A retrospective study was performed on 124 eligible
      patients (90 female and 34 male) suffering from cranial base meningioma that had
      been operated on between April 1996 and February 2003. The patients were
      classified according to LS and our modified grading systems. The modified grading
      system deploys six groups of variables: optic apparatus involvement, cavernous
      sinus neural involvement, facial-auditory involvement, caudal cranial nerve
      dysfunction, data derived from imaging studies (multiple fossa involvement and/or
      vessel encasement), and history of previous radiosurgery. Each criterion scores 1
      if present and the total score is the sum of scores obtained from the
      aforementioned criteria. RESULTS: Amongst 124 patients, 66 (52%) underwent gross
      total removal of the tumour. Regression and correlation analysis were performed
      for both LS (r(2) = 0.9683) and our modified grading systems (r(2) = 0.990) to
      evaluate the relationship of tumour grade versus the proportion of total
      resection. The correlations were significantly different (P < 0.01). CONCLUSION:
      Although the LS grading system is reported to be a good predictor of the extent
      of tumour resection, we believe that application of the six aforementioned
      variables will enhance the accuracy of this system, while preserving simplicity
      and communicability.

PMID- 16404640
TI  - Endoscopic third ventriculostomy in children: early and late complications and
      their avoidance.
AB  - INTRODUCTION: Endoscopic third ventriculostomy (ETV) is considered by many
      authors the initial surgical procedure of choice for the treatment of non
      communicant hydrocephalus. However, this procedure has early and late
      complications that neurosurgeons must be aware of when performing it. MATERIALS
      AND RESULTS: A retrospective study of infants and children treated with ETV at
      Children's Memorial Hospital (Chicago, IL) between 1993 and 2004 is presented. A
      total of 136 ETVs in 122 patients were performed with 8.8% early complication
      rate (hemorrhage, CSF leak, infection, diabetes insipidus, and seizures). There
      were no fatalities but one patient had severe neurological disturbances due to
      intracranial hemorrhage at the second ETV. We identified several significant
      factors that influence the late ETV failure rate: age under 12 months (p=0.012),
      cases performed early in our experience (p=0.009), patients with hydrocephalus
      without expansive lesions (p=0.026), patients that had an external ventricular
      drain (EVD) after ETV (p<0.005), and patients who developed early complications
      (p=0.035). CONCLUSION: A careful patient selection and preoperative planning lead
      to better results of ETV. A higher early and late complication rate in children
      younger than 1-year-old were noted in our series. There is definitely a learning
      curve for this technique, and several technical considerations are helpful to
      avoid adverse events. Most of the early complications are transient, while
      potential devastating injuries can occur. Long-term follow-up is needed to
      identify delayed closure of the fenestration. Ventricular access devise is
      helpful for diagnostic and therapeutic purposes during the follow-up.

PMID- 16404641
TI  - Hydrocephalus in intraspinal dermoids and dermal sinuses: the spectrum of an
      uncommon association in children.
AB  - BACKGROUND: Hydrocephalus associated with intraspinal tumors constitutes a well
      documented occurrence. The accepted mechanisms for this association seem to be
      well established. On the contrary, hydrocephalus in the context of intraspinal
      dermoids has been rarely recognized and its pathogenetic mechanism appears to be
      different. PATIENTS AND METHODS: The authors report four pediatric cases of
      spinal dermoid tumors and dermal sinuses that developed hydrocephalus during the
      evolution of these congenital lesions of ectodermal origin. DISCUSSION: In two
      children, the mechanism leading to the development of hydrocephalus consisted of
      leptomeningeal inflammation due to bacterial meningitis or to spillage of dermoid
      cyst contents in the cerebrospinal fluid spaces. We hypothesize that ventricular
      dilatation in the other two might be the result of chemical meningitis occurring
      during intrauterine life. Two cases developed ventriculomegaly prior to the
      diagnosis of their spinal cord disease. CONCLUSIONS: The unusual evolution of
      these cases suggests that neuroimaging studies that include the spine should be
      performed in cases of childhood "unexplained hydrocephalus".

PMID- 16404642
TI  - Ganglioglioma of optic chiasma: case report and review of literature.
AB  - CASE REPORT: We report a case of ganglioglioma of the optic chiasma in an 8-year
      old child who presented with gradual deterioration of vision since the age of 3
      years and complete loss by 8 years. REVIEW OF LITERATURE: Intensive literature
      search by the authors showed only 12 cases of ganglioglioma involving the visual
      pathway reported so far. Report on our case is presented here along with review
      of literature.

PMID- 16404643
TI  - Growing skull fractures.
AB  - INTRODUCTION: Growing skull fractures are a rare complication of head injuries
      (Ersahin et al. in Neurosurg Rev 23:139-144, 2000; Hayashi et al. in Childs Nerv
      Syst 13:349-351, 1997; Ramamurthi and Kalyanaraman in Neurosurgery 32:427-430,
      1970; Zegers et al. in Eur J Pediatr 162:556-557, 2003). Although early diagnosis
      and prompt treatment are important to prevent the underlying progressive brain
      damage, the clinical presentation and the morphological investigations are rarely
      specific or sensitive shortly after the trauma. DISCUSSION: The authors present
      three cases of growing skull fractures: the use of ultrasonography (US) via the
      fracture line contributed to early diagnosis and prompt treatment in two cases.
      US was not performed in the third case, and this delayed management. Treatment
      consisted of a watertight duraplasty with a free flap of pericranium without
      cranioplasty. US via the fracture line appears to be a sensitive and reliable
      method of detecting the dural tears in the early stages of growing skull
      fractures. CONCLUSION: Duraplasty alone with a flap of pericranium remains the
      simplest and least expensive method of treatment. Cranioplasty is not necessary
      in young children.

PMID- 16404644
TI  - Multiple genetic pathways for seed shattering in the grasses.
AB  - Shattering is an essential seed dispersal mechanism in wild species. It is
      believed that independent mutations at orthologous loci led to convergent
      domestication of cereal crops. To investigate genetic relationships of Triticeae
      shattering genes with those of other grasses, we mapped spike-, barrel- (B-type),
      and wedge-type (W-type) spikelet disarticulation genes in wheat and its wild
      relatives. The Br1 gene for W-type disarticulation was mapped to a region
      delimited by Xpsr598 and Xpsr1196 on the short arm of chromosomes 3A in Triticum
      timopheevii and 3S in Aegilops speltoides. The spike- and W-type disarticulation
      genes are allelic at Br1 in Ae. speltoides. The B-type disarticulation gene,
      designated as Br2, was mapped to an interval of 4.4 cM between Xmwg2013 and
      Xpsr170 on the long arm of chromosome 3D in Aegilops tauschii, the D-genome donor
      of common wheat. Therefore, B- and W-type disarticulations are governed by two
      different orthologous loci on group-3 chromosomes. Based on map position,
      orthologs of Br1 and Br2 were not detected in barley, maize, rice, and sorghum,
      indicating multiple genetic pathways for shattering in grasses. The implications
      of the mapping results are discussed with regard to the evolution of polyploid
      wheat and domestication of cereals.

PMID- 16404647
TI  - The results of periorbital rejuvenation with botulinum toxin A using two
      different protocols.
AB  - BACKGROUND: This study was proposed to analyze the changes in shape and position
      of the eyebrow before and after botulinum toxin A injection using two different
      protocols for a periorbital rejuvenation. METHODS: The botulinum toxin A
      treatment was performed for brow-lift and effacement of crow's feet (group A),
      and for brow-lift and effacement of glabellar frown lines in addition to crow'
      feet (group B). To evaluate the change in brow shape and height, measurements of
      five points around the brow were taken before and after treatment. RESULTS: In
      groups A and B, the brow positions were elevated, and the interbrow distance was
      increased. The central brow showed the largest elevation, followed by the lateral
      brow and the medial brow. The difference in the interbrow distance between groups
      A and B was statistically significant (p < 0.001). CONCLUSION: Elevation of the
      eyebrow with the desired aesthetically pleasing curvature was obtained after
      botulinum toxin A treatment in both groups using two different protocols for
      periorbital rejuvenation. The effect on the muscular dynamics after treatment can
      be changed according to the amount and the injection points. Therefore, in
      determining the injection protocols for periorbital rejuvenation, consideration
      should be given to the change in brow position and shape according to the change
      in the muscular dynamics after treatment.

PMID- 16404648
TI  - Augmentation/mastopexy: how to select and perform the proper technique.
AB  - During a period of 8 years, 384 female patients underwent simultaneous surgery
      for placement of implants and mastopexy. The surgical techniques used were
      selected according to the characteristics of each particular case. The
      determining variables in the selection were ptosis of the nipple-areola complex
      (NAC) and distance from the NAC to the inframammary fold. Only three surgical
      techniques were used: NAC lifting (n = 30), periareolar pexy (n = 196), and
      inverted T pexy (n = 158). The degree of general satisfaction with each of the
      techniques was 89%, 82%, and 92%, respectively. Round and anatomic implants were
      used, respectively, for 258 (67%) and 126 (33%) of the patients, with their use
      depending on the medical indications and each patient's choice. All complications
      were minor, and their overall incidence was 18%. Factors such as proper choice of
      the surgical technique, type of implant, approach to placement of the implant,
      type of suture, and removal of tissue for the pexy are fundamental to obtaining a
      good result. With these factors kept in mind, it is possible to perform the
      combined procedure of mastopexy and implantation, to minimize the complications,
      and to obtain satisfactory results over the mid and long terms.

PMID- 16404649
TI  - Linear hypopigmentation after triamcinolone injection: a rare complication of a
      common procedure.
AB  - The development of linear hypopigmentation after intralesional or intraarticular
      injection of triamcinolone acetonide has been reported in the literature as a
      very rare side effect. This case report describes a patient with linear
      hypopigmentation and discusses the possible pathophysiology. Clinicians involved
      in the care of hypertrophic scars and keloids need to be aware of this rare side
      effect so that they can guide their patients appropriately. They need to
      understand the pathogenesis of this complication better so that it may become
      avoidable.

PMID- 16404650
TI  - Abdominoplasty with total abdominal liposuction for patients with massive weight
      loss.
AB  - BACKGROUND: Massive weight loss after bariatric surgery is associated with
      significant skin excess, laxity, and ptosis over the abdomen. Good results have
      been achieved with abdominoplasty and circumferential lipectomy. However, blood
      transfusions are sometimes needed, and patients may require long hospital stays.
      Furthermore, morbidity rates are high. Total abdominal liposuction performed with
      abdominoplasty allows for the preservation of lymphatic vessels below Scarpa's
      fascia and eliminates the need for upper flap undermining. This study aimed to
      evaluate this technique in patients with anterior abdominal redundancy
      attributable to massive weight loss after bariatric surgery. METHODS: The charts
      of 60 patients treated between December 2001 and October 2004 were
      retrospectively reviewed. All the patients had undergone previous bariatric
      surgery as well as subsequent total abdominal liposuction and abdominoplasty.
      RESULTS: The average amount of wetting solution used was 3.1 l, and the average
      total aspirate was 2.5 l. The mean pannus weight was 3,649 g, and the average
      dimension was 48 x 25 x 6 cm. No patient required a blood transfusion. The median
      in-hospital stay was 1 day, with 42% of the patients treated as outpatients. The
      median follow-up period was 3 months. Morbidity was 22%. Factors associated with
      the development of complications were weight of the pannus, transverse dimension
      of the pannus, and body mass index. All the patients were satisfied with the
      results. CONCLUSIONS: Total abdominal liposuction followed by abdominoplasty is
      adequate treatment for anterior abdominal redundancy for patients with massive
      weight loss.

PMID- 16404651
TI  - A retrospective study on the use of a low-molecular-weight heparin for
      thromboembolism prophylaxis in large-volume liposuction and body contouring
      procedures.
AB  - This retrospective study was designed to evaluate the efficacy of low-molecular
      weight heparin (enoxeparin) as a prophylaxis for venous thromboembolism and deep
      venous thrombosis (DVT) in the management of large-volume liposuction, added body
      contouring procedures, or both. The author present an 18-month experience with
      the use of this therapy for 291 consecutive patients. All the patients fell into
      the categories of high risk and highest risk for the development of deep vein
      thrombosis, embolism, or both. Three patients experienced transient DVT-like
      symptoms and underwent a thorough workup by an independent highly specialized
      critical care medical team. The results were found ultimately to be inconclusive
      for DVT and pulmonary embolism. However, all the patients experienced a complete
      recovery. The results show a 0% incidence of DVT and pulmonary embolism among
      patients who received enoxeparin as prophylaxis. The medication did not
      precipitate major bleeding when administered 1 h after surgery. This study offers
      the first report that describes the use of enoxeparin in aesthetic surgery for
      high-risk patients. The authors feel the need to inform their colleagues of the
      benefits obtained over the past 18 months by incorporating this therapy in large
      volume liposuction and extensive body-contouring procedures performed during the
      same operative session. This study was conducted by a highly experienced surgical
      team in a fully accredited outpatient facility with established protocols for
      handling these types of procedures on a daily basis. The authors are optimistic
      about the results, and the use of enoxeparin is now part of their postoperative
      regimen in high-risk aesthetic surgery cases.

PMID- 16404652
TI  - Lipoabdominoplasty: liposuction with reduced undermining and traditional
      abdominal skin flap resection.
AB  - Abdominoplasty surgery has spread universally, as both an aesthetic and a
      reconstructive procedure, and new techniques are appearing with the goal of
      minimizing ischemic complications of the flap and bettering body contour. The
      purpose of this article is to demonstrate that an abdominoplasty technique with
      limited undermining and preservation of the flap perforator vessels makes it
      possible to reduce the complication rate attributable to flap necrosis and seroma
      in abdominoplasty. Doppler flowmetry color study of the abdominal wall was
      performed before the surgical procedure and on postoperative day 15 after
      lipoabdominoplasty for a series of 20 patients to evaluate the blood supply of
      the abdominal wall. This study confirmed the preservation of perforator arteries
      in the periumbilicus area and right upper quadrant after abdominoplasty with
      liposuction and reduced undermining.

PMID- 16404653
TI  - Interaction of botulinum toxin type A with local anesthetic agents: an
      experimental study with rabbits.
AB  - Injection of botulinum toxin is a painful procedure, limiting the number of
      patients treated. This study was designed to establish whether infiltration of
      local anesthetics plays a role in the effectiveness of botulinum toxin. For the
      study, 24 New Zealand white rabbits were divided into three groups. In all three
      groups, local anesthetics (prilocaine, lidocaine, lidocaine, and epinephrine)
      were injected into the right anterior auricular muscle before a 2.5-U injection
      of botox A. The contralateral anterior auricular muscle of all the rabbits was
      injected with the same dose of the toxin to serve as a control. Photographic
      documentation was recorded; electromyographic study was performed; and results
      were statistically analyzed. The results show that local anesthetics do not play
      a role in the efficacy of botulinum toxin. Thus, the use of infiltrative local
      anesthetics before botulinum toxin injection is a safe method for achieving a
      less painful procedure for the patient.

PMID- 16404654
TI  - Geostatistical analysis for hydrogeochemical characterization of the Han River,
      Korea: identification of major factors governing water chemistry.

PMID- 16404655
TI  - Tolerable level of lifetime cadmium intake estimated as a benchmark dose low,
      based on excretion of beta2-microglobulin in the cadmium-polluted regions of the
      Kakehashi River Basin, Japan.

PMID- 16404656
TI  - Relationship between dietary cadmium absorption by grass shrimp (Palaemonetes
      pugio) and trophically available cadmium in amphipod (Gammarus lawrencianus)
      prey.

PMID- 16404657
TI  - Determination of in vitro biotoxicity in exhaust particulate matter from heavy
      duty diesel engine.

PMID- 16404658
TI  - Aftermath of the long-term application of sludge and water from a sewage
      treatment plant to a lemon tree (Citrus limon) plantation.

PMID- 16404659
TI  - Impact of 1,4-dioxane from domestic effluent on the Agano and Shinano Rivers,
      Japan.

PMID- 16404660
TI  - Toxicity to Daphnia magna, Hyalella azteca, Oncorhynchus kisutch, Oncorhynchus
      mykiss, Oncorhynchus tshawytscha, and Rana catesbeiana of atrazine, metolachlor,
      simazine, and their formulated products.

PMID- 16404661
TI  - Acute toxicity of the synthetic pyrethroid deltamethrin to fingerling European
      catfish, Silurus glanis L.

PMID- 16404662
TI  - Toxicity of sediment from a mining spill to Cylindrotheca closterium (Ehremberg)
      Lewin and Reimann (Bacillariophyceae).

PMID- 16404664
TI  - Pilot study of polycyclic aromatic hydrocarbons in surface soils of Guiyang City,
      People's Republic of China.

PMID- 16404663
TI  - Comparative sensitivity of freshwater algae to atrazine.

PMID- 16404665
TI  - Treatment of polluted river water using pilot-scale constructed wetlands.

PMID- 16404666
TI  - Preparation and performance of inorganic coagulant for landfill leachate
      pretreatment.

PMID- 16404667
TI  - Photochemical transformation of bisphenol a promoted by nitrate ions.

PMID- 16404668
TI  - Bisphenol A in the surface water and freshwater snail collected from rivers
      around a secure landfill.

PMID- 16404669
TI  - Use patterns and residue levels of pesticides on Mukunuwenna, a leafy vegetable
      grown in Sri Lanka.

PMID- 16404670
TI  - Abamectin in tea and tea liquor under northeastern Indian climatic conditions.

PMID- 16404671
TI  - Bioaccumulation of heavy metals, organochlorine pesticides, and detoxication
      biochemical indexes in tissues of Ictalurus melas of Lake Trasimeno.

PMID- 16404673
TI  - Polybrominated diphenyl ethers and polychlorinated biphenyls in different tissue
      types from chinook salmon (Oncorhynchus tshawytscha).

PMID- 16404672
TI  - Ecochemical approach using mercury accumulation of Antarctic minke whale,
      Balaenoptera bonaerensis, as tracer of historical change of Antarctic marine
      ecosystem during 1980-1999.

PMID- 16404674
TI  - Organotin compounds in the Three Gorges Reservoir region of the Yangtze River.

PMID- 16404675
TI  - Heavy metal accumulation of edible vegetables cultivated in agricultural soil in
      the suburb of Zhengzhou City, People's Republic of China.

PMID- 16404676
TI  - On the adsorption mechanisms of copper ions over modified biomass.

PMID- 16404677
TI  - Adsorption of Cu2+ on montmorillonite as affected by 2,4-dichlorophenoxyacetic
      acid (2,4-D).

PMID- 16404679
TI  - Promoting healthy organizational partnerships and collaboration between consumer
      run and community mental health agencies.
AB  - Community mental health agencies (CMHAs) and consumer-run agencies (CRAs) both
      provide critically important services to persons with severe psychiatric
      disabilities. Emerging research has begun to support the effectiveness of the CRA
      approach, a newer service delivery mechanism. However, collaboration between the
      two service systems, when it occurs, is often problematic. This article briefly
      identifies the core features of CRAs, discusses their potential for collaboration
      with CMHAs, and suggests ways to promote healthy organizational partnerships
      between the two based upon the model proposed by Gidron and Hasenfeld [(1994)
      Nonprofit Management & Leadership, 5(2), 159-172]. Salient collaboration theories
      are reviewed and barriers to collaboration are discussed. Finally, implications
      for mental health practice and future research directions are identified.

PMID- 16404680
TI  - The mental health of federal offenders: a summative review of the prevalence
      literature.
AB  - To date, only a small number of government and peer-reviewed studies have
      examined the mental health of federal offenders. Although these studies provide
      isolated bits of information they have yet to be organized into a coherent body
      of knowledge from which clinicians, administrators and policy makers can inform
      their work. As a first step in constructing this knowledge and understanding the
      possible mental health needs of this population (currently America's largest
      correctional population), this paper delineates the available government and peer
      reviewed studies on federal offenders, highlights their convergent findings, and
      suggests opportunities for growth in research, administration and policy.

PMID- 16404678
TI  - Hypnotic treatment of chronic pain.
AB  - This article reviews controlled trials of hypnotic treatment for chronic pain in
      terms of: (1) analyses comparing the effects of hypnotic treatment to six types
      of control conditions; (2) component analyses; and (3) predictor analyses. The
      findings indicate that hypnotic analgesia produces significantly greater
      decreases in pain relative to no-treatment and to some non-hypnotic interventions
      such as medication management, physical therapy, and education/advice. However,
      the effects of self-hypnosis training on chronic pain tend to be similar, on
      average, to progressive muscle relaxation and autogenic training, both of which
      often include hypnotic-like suggestions. None of the published studies have
      compared hypnosis to an equally credible placebo or minimally effective pain
      treatment, therefore conclusions cannot yet be made about whether hypnotic
      analgesia treatment is specifically effective over and above its effects on
      patient expectancy. Component analyses indicate that labeling versus not labeling
      hypnosis treatment as hypnosis, or including versus not including hand-warming
      suggestions, have relatively little short-term impact on outcome, although the
      hypnosis label may have a long-term benefit. Predictor analyses suggest that
      global hypnotic responsivity and ability to experience vivid images are
      associated with treatment outcome in hypnosis, progressive relaxation, and
      autogenic training treatments. The paper concludes with a discussion of the
      implications of the findings for future hypnosis research and for the clinical
      applications of hypnotic analgesia.

PMID- 16404681
TI  - The role of social networks and support in postpartum women's depression: a
      multiethnic urban sample.
AB  - OBJECTIVES: This study examined the relationship of social support, and of social
      networks, to symptoms of depression in a multiethnic sample of women having
      recently given birth. METHODS: Women at community health centers in a
      Northeastern city were randomly sampled from groups stratified by race/ethnicity
      (African American, Hispanic, and White) and postpartum interval. Mother's score
      on the Center for Epidemiologic Studies of Depression Scale (CES-D) was the
      dependent variable. Main independent variables included the Medical Outcomes
      Study (MOS) Social Support Survey and a social network item. Univariate
      statistics assessed the relationship between CES-D score and each of the
      independent variables. Multivariate linear regression models included core
      sociodemographic variables alone, the core model with each of the social support
      and social network variables added separately, and all variables together. We
      evaluated interactions between race and social support, race and social networks,
      and social support and social networks. RESULTS: The multivariate models with MOS
      Social Support and core variables indicated that each 10-point increase in the
      MOS Social Support Survey was related to a 2.1-unit lower score on the CES-D (95%
      CI -2.4, -1.7). The inclusion of the social network variable into the core model
      showed that having two or more friends or family members available was associated
      with a 13.6-point lower mean score on the CES-D (95% CI -17.5, -9.6), compared to
      women reporting none or only one available person. CONCLUSIONS: Both social
      support and social networks were statistically significant and independently
      related to depressive symptomatology.

PMID- 16404682
TI  - Determinants of care satisfaction among inpatients with schizophrenia.
AB  - Satisfaction with inpatient psychiatry can promote positive treatment outcomes.
      Using information on 315 inpatients with schizophrenia, this study tested the
      hypothesis that some services promote more satisfaction than others. Relative to
      less satisfied counterparts, inpatients were more likely to approve of care if
      staff invested high levels of effort into education about: (1) control of
      symptoms with psychiatric medication, (2) adverse effects of stress on symptoms,
      and (3) social skills. Other services were appreciated less. In order to enhance
      intervention outcomes, the findings suggest that limited resources should be
      invested to a greater extent in practices that are valued most highly by
      patients.

PMID- 16404683
TI  - Active medical conditions among patients on an assertive community treatment
      team.
AB  - The purpose of this cross-sectional study was to examine the number and type of
      active medical conditions among psychiatric patients treated by an assertive
      community treatment (ACT) team in an urban setting. Psychiatric hospitalization
      admission and discharge summaries of 70 patients were reviewed, and case managers
      on the treatment team were interviewed. Patients had a median of three active
      medical conditions. Osteoarthritis, hypertension, viral Hepatitis C infection,
      gastroesophageal reflux disease (GERD), and reactive airway disease were the most
      common active medical illnesses. The majority of patients were cigarette smokers
      and were diagnosed with alcohol or illicit substance use disorders, which were
      associated with viral hepatitis C infection and reactive airway disease in this
      patient population.

PMID- 16404684
TI  - Updates and five-year evaluation of the S.A.F.E. program: a family
      psychoeducational program for serious mental illness.
AB  - This brief report reviews recent updates to the S.A.F.E. Program, a family
      psychoeducational intervention for serious mental illness created in the Veterans
      Affairs (VA) system. The improvements and significant content additions to the
      curriculum are outlined. Further, positive five-year program evaluation data are
      described, including high levels of participant retention and satisfaction.
      Program attendance is positively correlated with understanding of mental illness,
      awareness of VA resources, and ability to engage in self-care activities-and
      inversely correlated with caregiver distress. This data lays the groundwork for a
      randomized clinical trial and raises questions about the necessity of diagnostic
      specific family programming.

PMID- 16404685
TI  - Demographic characteristics and employment among people with severe mental
      illness in a multisite study.
AB  - People with psychiatric disabilities experience disproportionately high rates of
      unemployment. As research evidence is mounting regarding effective vocational
      programs, interest is growing in identifying subgroup variations. Data from a
      multisite research and demonstration program were analyzed to identify
      demographic characteristics associated with employment outcomes, after adjusting
      for the effects of program, services, and study site. Longitudinal analyses found
      that people with more recent work history, younger age, and higher education were
      more likely to achieve competitive employment and to work more hours per month,
      while race and gender effects varied by employment outcome. Results provide
      strong evidence of demographic subgroup variation and need.

PMID- 16404686
TI  - The mental health of children exposed to maternal mental illness and
      homelessness.
AB  - In recent years a number of reports have documented an increase in the number of
      homeless families in the US. Using a sample of 195 mothers who were veterans of
      the US armed forces we assessed the association of maternal homelessness and
      clinical status, with measures of children's mental health, school enrollment and
      attendance. Although maternal homelessness had no significant association with
      children's reported emotional problems it had a profound effect on school
      enrollment and attendance. Mothers' mental health status, history of
      incarceration and cumulative history of trauma, as well as children's exposure to
      trauma and their self-esteem were the factors most strongly associated with
      measures of children's emotional problems. The study suggests that preventive
      interventions are needed to minimize the effects of exposure to trauma, both in
      the community and at home, as well as family interventions to address both the
      mother's and child's emotional and physical needs. A longitudinal study is needed
      to understand better the association between residential instability and
      children's mental health.

PMID- 16404687
TI  - Commodity fetichismo, the Holy Spirit, and the turn to Pentecostal and African
      Independent Churches in Central Mozambique.
AB  - Pentecostal and African Independent Churches have rapidly spread throughout
      central Mozambique in the aftermath of war and in the midst of a recent
      structural adjustment program that has hastened commoditization of community life
      and intensified local inequalities. This extraordinary expansion signals a shift
      away from reliance on "traditional" healers to treat persistent afflictions
      believed to have spiritual causes. Survey data and illness narratives collected
      from recent church recruits and local residents during research in 2002 and 2003
      in the city of Chimoio reveal that healers have increased fees and tailored
      treatments to clients searching for good fortune in ways that have alienated many
      other help seekers in this changing social environment. While traditional healing
      has been celebrated in the international health world, community attitudes are
      less generous; many healers are increasingly viewed with suspicion because of
      their engagement with malevolent occult forces to foment social conflict,
      competition, and confrontation for high fees. Church healing approaches offer
      free and less divisive spiritual protection reinforced by social support in a new
      collectivity. One vital source of church popularity derives from pastors' efforts
      to tap the already considerable community anxiety over rising healer fees and
      their socially divisive treatments in an insecure environment.

PMID- 16404688
TI  - Transnational medicine in public arenas: AIDS treatments in the South.
AB  - This article looks at the AIDS-related controversy surrounding the experiments on
      and the availability of medicines in southern countries. It situates these
      debates in a longer-term history of transnational medicine. It highlights the
      rise of international therapeutic modernity at the beginning of the 1990s, based
      on the strict regulation of clinical trials and on the formalization of the
      international ethical rules governing experiments. This rise helped to change
      radically the reception of experiments conducted in southern countries around
      AIDS. With regard to this new ethics applied to clinical trials in southern
      countries, this article goes on to demonstrate the confrontation at the end of
      the 1990s between two different approaches to the universalization of healthcare.
      Finally, it shows how new laws on international trade have reinitiated this
      confrontation. Through this story, the article suggests in what sense the study
      of the political transformations of transnational medicine could offer a new
      field of investigation for the social sciences.

PMID- 16404689
TI  - Stressors, supports and the social ecology of displacement: psychosocial
      dimensions of an emergency education program for Chechen adolescents displaced in
      Ingushetia, Russia.
AB  - This study explored the psychosocial benefits of an emergency education
      intervention serving adolescents displaced by the war in Chechnya. It set out to
      describe key stressors and sources of social support available to youth served by
      the International Rescue Committee's (IRC) emergency education program.
      Interviews were conducted with 57 Chechen adolescents living in spontaneous
      settlements in Ingushetia, Russia in the fall of 2000. Of particular interest was
      the degree to which the education program addressed specified psychosocial goals.
      Findings indicated that young people and their families faced a number of
      physical and emotional stressors. The data indicated that the emergency education
      program provided benefits by enriching sources of social support, providing
      meaningful activity and a sense of hope for the future, and creating a space for
      young people to spend time and connect to others. However, the contrast between
      the desire of adolescents "to live like other kids" and the options available to
      them presented a dilemma for the emergency education program: adolescents craved
      normalcy, but for any intervention to be delivered, it had to first begin with
      creative and adaptive strategies that were by no means a complete replacement for
      formal, mainstream education. The programmatic and policy implications of these
      findings are presented here.

PMID- 16404690
TI  - Narrating kidney disease: the significance of sensation and time in the
      emplotment of patient experience.
AB  - Drawing on research conducted among patients in Ireland, this article examines
      the narrative constructions of chronic kidney failure and explores the ways in
      which patient narratives cross-cut and subvert modernist medical constructions of
      transplantation as a therapeutic outcome, an endgame, a "gift of life." In
      experience, patients dismantle this construction structure by emplotting their
      stories around the painful lack of an ending, ardently brought to bear by the
      lived realities of immunosuppressant drug therapy, the silent fears of graft
      rejection, and the isolation of recipiency. They articulate, instead, stories
      that disclose a multi-directional flow between past and future therapeutic
      interventions, between the altering nature of the renal body and personal
      experience. These storied dimensions are phenomenologically embedded in the
      sensory and temporal aspects of this condition as essential elements of chronic
      illness and as organizational properties of patient narratives.

PMID- 16404691
TI  - Commentary: deconstructing critiques on the internationalization of PTSD.
AB  - When PTSD entered the DSM, advocacy for the diagnosis was a critical part of
      advocacy for Vietnam veterans. Over the next two decades, the range of contexts
      in which this clinical concept was applied increased dramatically. In a recent
      article in Culture, Medicine and Psychiatry, Breslau (2004) describes PTSD as a
      "prominent cultural model" to account for suffering as well as the synergy
      between human rights or political advocacy and traumatic stress advocacy. In this
      article I question the sequence of steps that Breslau took to critique the
      internationalization of the PTSD construct. I also question Breslau's critique on
      our work in Nepal. Finally, I will formulate some future challenges for
      psychiatry and anthropology to bridge their universalistic and relativistic
      points of view.

PMID- 16404694
TI  - Can information technology help in acute dialysis therapy?

PMID- 16404693
TI  - The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event.
AB  - Both the extent and location of the maternal ancestral deme from which the
      Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the
      maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of
      Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women
      carrying distinct mtDNAs that are virtually absent in other populations, with the
      important exception of low frequencies among non-Ashkenazi Jews. We conclude that
      four founding mtDNAs, likely of Near Eastern ancestry, underwent major
      expansion(s) in Europe within the past millennium.

PMID- 16404695
TI  - Do we have reliable biochemical markers to predict the outcome of critical
      illness?
AB  - Current outcome prediction in critically ill patients relies on the art of
      clinical judgement and/or the science of prognostication using illness severity
      scores. The biochemical processes underlying critical illness have increasingly
      been unravelled. Several biochemical markers reflecting the process of
      inflammation, immune dysfunction, impaired tissue oxygenation and endocrine
      alterations have been evaluated for their predictive power in small
      subpopulations of critically ill patients. However, none of these parameters has
      been validated in large populations of unselected ICU patients as has been done
      for the illness severity and organ failure scores. A simple biochemical predictor
      of ICU mortality will probably remain elusive because the processes underlying
      critical illness are very complex and heterogeneous. Future prognostic models
      will need to be far more sophisticated.

PMID- 16404696
TI  - A comparison of two citrate anticoagulation regimens for continuous veno-venous
      hemofiltration.
AB  - AIMS: To assess the safety and efficacy of two different commercial citrate
      containing pre-filter replacement fluids during continuous veno-venous
      hemofiltration (CVVH) in patients with frequent filter clotting. SETTING: Four
      intensive care units. PATIENTS: Sixty-three critically ill patients with acute
      renal failure (ARF). DESIGN: Prospective observational study. METHODS: We used a
      commercial citrate fluid (citrate: 11 mmol/L -fluid A) as predilution replacement
      for CVVH. We then changed to a new commercial citrate fluid (citrate: 14 mmol/L
      fluid B) as replacement fluid and performed statistical comparisons. Replacement
      fluid rate was fixed at 2,000 ml/hour. RESULTS: Filter life was 12.2 hour with
      fluid A compared with 17.1 hour with fluid B on average (p=0.0001). Mean post
      filter ionized calcium concentration was 0.52 mmol/L with fluid A compared with
      0.40 mmol/L with fluid B (p<0.0001). Citrate intolerance led to cessation of
      treatment in one patient with fluid A and one patient with fluid B. Overall
      ionized calcium levels were higher (A: 1.18 vs B: 1.13 mmol/L; p<0.0001) and
      bicarbonate was lower (A: 22.4 vs B: 24.5 mmol/L; p<0.0001) during treatment with
      fluid A. Alkalemia was seen in 10 patients treated with fluid A and 16 patients
      treated with fluid B (NS). CONCLUSIONS: We have developed a simple approach to
      regional citrate anticoagulation for CVVH using a commercial citrate-containing
      fluid as replacement fluid. Increasing citrate concentration from 11 to 14 mmol/L
      increased filter life while maintaining relative safety and simplicity.

PMID- 16404697
TI  - The impact of various cycling regimens on phosphorus removal in chronic
      peritoneal dialysis patients.
AB  - BACKGROUND: The National Kidney Foundation Dialysis Outcome Quality Initiative
      clinical practice guidelines have suggested that serum phosphate levels be
      maintained at < or =5.5 mg/dL in patients maintained on dialysis. Over 45% of
      anuric patients maintained on CAPD have serum phosphate levels >5.5 mg/dL. The
      present study was designed to address the question whether phosphate removal
      could be enhanced by increasing the dialysate volume during cycler peritoneal
      dialysis therapy. METHODS: Medically stable patients maintained on chronic
      peritoneal dialysis therapy, who were high or high-average transporters and had
      serum phosphate levels > or =5.5 mg/dL, were invited to participate in the study.
      The protocol involved measuring phosphate and creatinine clearances at weekly
      intervals on three different cycler prescriptions consisting of 7 and 12 full
      cycles or 24 cycles with 50% tidal PD (TPD) over 9 hours. Ten patients agreed to
      participate. Those patients (n=7) with a BMI > 22 had 2 liter (L) fill volumes
      and 14 L of total dialysate (7 cycles of 2 L) or 24 L total dialysate (12 cycles
      of 2 L or 50% TPD with 24 cycles).The patients (n=3) with a BMI < 20 had 1.2 L
      fill volumes and 8.4 L total dialysate (7 cycles) or 14.4 L total dialysate (12
      cycles of 1.2 L or 50% TPD with 24 cycles). RESULTS: The mean age (+/- SD) of the
      study patients was 50.8 (+/- 9.3) years. There were 6 females, 6 Caucasians and 4
      African-Americans. The mean weight of the patients was 71.5 (+/- 24.2) kg and
      mean height 1.65 (+ 7.6) meters. The mean BMI was 18.3 (+/- 1.27) in the < 20 BMI
      group and 30.3 (+/- 6.6) in the > 22 BMI group. The mean phosphate clearance
      (L/night/1.73m 2 ) increased from 3.96 (+/- 1.16) with 7 cycles to 4.71 (+ 1.81)
      with 12 cycles and 4.51 (+/- 1.61) with 50% TPD. Creatinine clearance
      (L/night/1.73m 2 ) was 4.74 (+/- 1.74) with 7 cycles, 6.06 (+/- 2.04) with 12
      cycles and 5.61 (+/- 2.01) with TPD. CONCLUSION: The present study indicates that
      there is a significant, 19% (P < 0.005) rise in phosphate clearance by increasing
      dialysate volume 71% from 7 cycles to 14 cycles compared to a 27% increase in
      creatinine clearance. With tidal PD, phosphate clearance increased by 12% (p=NS)
      and creatinine clearance increased 18 % (p, 0.02). This increase in phosphate
      clearance translates into <50 mg net phosphate removal in 9 hours, assuming a
      serum phosphate of 6 mg/%. Thus, increasing dialysis cycles and volume results in
      only a minimal increase in net phosphate removal.

PMID- 16404698
TI  - Life-threatening complications of extracorporeal treatment in patients with
      severe eosinophilia.
AB  - We report three patients with massive eosinophilia of different etiology who
      developed bronchoconstriction, hypotension, and shock shortly after dialysis or
      leukapheresis had been begun. In two cases, ethylene oxide-free materials had
      been used ruling out an allergic reaction related to this compound. Degranulation
      of eosinophils with release of eosinophil peroxidase may have caused the observed
      adverse reactions, as suggested by in vitro experiments with blood from the three
      patients. Our observations draw attention to the fact that extracorporeal
      therapies may initiate life-threatening complications in patients with severe
      eosinophilia.

PMID- 16404699
TI  - Hospitalization in hemodialysis patients in one region of Lithuania.
AB  - INTRODUCTION AND METHODS: The objective of our study was to evaluate
      hospitalization rates in hemodialysis patients in the region of Kaunas, the
      second largest city in Lithuania. We analysed ambulatory case records of 187 ESRD
      patients dialysed in all 7 hemodialysis centers in the Kaunas region over the
      year 2002. RESULTS: During the year 2002 the unadjusted hospitalization rate over
      a 1 year period in all dialysed patients (the prevalent patients, n=187) was 1.4
      hospitalizations per patient year at risk. There were 17.5 hospital days per
      patient year at risk, the mean length of one hospitalization being 12.5 days. The
      most frequent causes of hospitalization were cardiovascular diseases (25%),
      infections (22%), and access related complications (10%). Of the 187 patients, 55
      started hemodialysis in the year 2002 (incident patients). The comparison of
      prevalent patients with incident patients revealed a higher hospitalization rate
      in the incident patients (unadjusted hospitalization rate was 1.9
      hospitalizations per patient year at risk). The length of hospitalization (29.1
      hospital days per patient year at risk) and the mean length of one
      hospitalization (15.1 days) were longer in the incident patients than the
      prevalent patients. In the year 2002, the National Sickness Fund paid $361 per
      year for hospitalizations of one hemodialysis patient and $10,800 per year for
      the dialysis procedures of one hemodialysis patient. CONCLUSIONS: The
      hospitalization rate in Lithuania for patients undergoing hemodialysis is similar
      to that of other European countries while hospitalization costs are lower.

PMID- 16404700
TI  - A mechanical model lung for hydraulic testing of total liquid ventilation
      circuits.
AB  - A new model lung (ML), designed to reproduce the tracheal pressure vs. fluid flow
      relationship in animals undergoing total liquid ventilation (TLV) trials, was
      developed to be used as a mock bench test for neonatal TLV circuits. The ML is
      based on a linear inertance-resistance-compliance (LRC) lumped-parameter model of
      the respiratory system with different resistance values for inspiration (R insp )
      or expiration (R exp ). The resistant element was set up using polypropylene
      hollow fibres packed inside a tube. A passive one-way valve was used to control
      the resistance cross-section area provided for the liquid to generate different
      values for R insp or R exp , each adjustable by regulating the active length of
      the respective fibre pack. The compliant element consists of a cylindrical column
      reservoir, in which bars of different diameter were inserted to adjust compliance
      (C). The inertial phenomena occurring in the central airways during TLV were
      reproduced by specifically dimensioned conduits into which the endotracheal tube
      connecting the TLV circuit to the ML was inserted. A number of elements with
      different inertances (L) were used to simulate different sized airways. A linear
      pressure drop-to-flow rate relationship was obtained for flow rates up to 5
      l/min. The measured C (0.8 to 1.3 mL cmH2O (-1) kg(-1)), R insp (90 to 850 cmH2O
      s l(-1)), and R exp (50 to 400 cmH2O s l(-1)) were in agreement with the
      literature concerning animals weighing from 1 to 12 kg. Moreover, features
      observed in data acquired during in vivo TLV sessions, such as pressure
      oscillations due to fluid inertia in the upper airways, were similarly obtained
      in vitro thanks to the inertial element in the ML.

PMID- 16404701
TI  - A stimulation unit for the application of mechanical strain on tissue engineered
      anulus fibrosus cells: a new system to induce extracellular matrix synthesis by
      anulus fibrosus cells dependent on cyclic mechanical strain.
AB  - A bioreactor system consisting of a multifunctional stimulation unit and common 6
      well culture plate is introduced to activate extracellular matrix synthesis in
      intervertebral disc cells due to cyclic mechanical strain. The developed
      stimulation unit is sterilizable and reusable. It is viable for cultivation and
      mechanical stimulation of cartilage tissue and tissue engineered cell matrix
      constructs in combination with the common 6-well culture plate. The custom made
      device allows long-term cultivations in batch- or continuous operation mode.
      Manual handling and thereby the risk of contamination is reduced. Sampling,
      changing the medium, and addition of supplements are easily performed from the
      connected conditioning vessel. This bioreactor system enables stimulation of
      different samples independently during one run. For the work presented here
      anulus fibrosus cells from pigs were taken and immobilized in agarose to obtain
      three-dimensional cell matrix constructs. Over a period of 14 days the constructs
      were subjected to 10% compression under cyclic mechanical pressure with a
      frequency of 0.1 Hz. Afterwards the constructs were biochemically examined for
      hydroxyproline and sulphated glycosaminoglycanes. These proven constituents of
      extracellular matrix were found to be released depending on the applied
      compressive strain.

PMID- 16404702
TI  - Effects of modified collagen matrices on human umbilical vein endothelial cells.
AB  - The most commonly used biomaterials fail to ensure sufficient angiogenesis for
      fast in vivo incorporation. This results in central necrosis and consequent
      infection. One way of obtaining a high angiogenic response is the application of
      vascular endothelial growth factor (VEGF). To obtain a sustained release of these
      cytokines, heparin was incorporated into collagen matrices using 1-ethyl-3(3
      dimethyl-aminopropyl) carbodiimide (EDC) and N-hydroxysuccinmide (NHS). The
      functionality of the heparinized collagen matrices was then enhanced by
      immobilization of VEGF via its heparin-binding domain. This procedure changed in
      vitro degradation behavior and water-binding capacity. Accelerated endothelial
      cell proliferation was also achieved. A range of different heparin and EDC/NHS
      concentrations in combination with VEGF induced variation in endothelial cell
      growth and tubulogenic formation. Polymerized collagen scaffolds presented
      biointeractive systems with integrated angiogenic activity. This may become a
      useful tool in the clinical therapy of disorders connected with wound healing.

PMID- 16404703
TI  - Cell dynamics in the correct control of bone metabolism using natural treatments.
AB  - The present study was undertaken in order to assess the efficacy of a commercial
      product containing calcium and silicon (Osteosil-Calcium) on cell metabolism. MG
      63 osteblast-like cells were cultured in the presence of three different drug
      concentrations (10, 5 and 2.5 microg/mL). Either serum-free culture and standard
      culture with serum were investigated. Morpho-functional tests (MTT and ALP),
      scanning electron microscopy (SEM), microanalysis (EDAX) and time-lapse video
      microscopy were performed. Cell actin cytoskeletal modification with fluorescence
      phalloidin staining was also tested. Our data show the in vitro functional
      efficacy of Osteosil-Calcium on MG63 cell viability and ALP production. This
      study demonstrates its positive effect on the metabolism of the single cell and
      suggests wider uses of this drug in health protection and or in Regenerative
      Medicine therapies which are currently applied to the elderly.

PMID- 16404704
TI  - Effect of hirudin versus heparin on hemocompatibility of blood contacting
      biomaterials: an in vitro study.
AB  - Hirudin serves as an alternative anticoagulant for extracorporeal blood
      circulation. Comparing anticoagulation with hirudin (2.5 or 5.0 microg/mL) and
      heparin (2.0 or 4.0 IU/mL) human blood was circulated in a modified 'Chandler
      System' using PVC-tubes for 2 hours at 37 degrees C. Activation of coagulation
      (thrombin-antithrombin III-complex, prothrombin fragment 1+2 and D-Dimer),
      platelet (platelet factor 4 - PF4) and complement systems was analyzed. Both
      heparin concentrations and 5.0 microg/dL hirudin led to as significantly less
      activated plasmatic coagulation as 2.5 microg/dL hirudin. Decreased levels of PF4
      and anaphylatoxin C5a (p<0.05) as well as terminal complement complex
      demonstrated improved hemocompatibility after anticoagulation with heparin in
      contrast to hirudin. Because initial coagulation cascade, platelet activation and
      complement activation is less influenced by hirudin than by heparin,
      hemocompatibility is more dependent on the characteristics of the biomaterials
      used. This predestines hirudin as anticoagulant for in vitro studies analyzing
      hemocompatibility of biomaterials or surface modifications.

PMID- 16404705
TI  - Inhibitory effects of black tea theaflavin derivatives on 12-O
      tetradecanoylphorbol-13-acetate-induced inflammation and arachidonic acid
      metabolism in mouse ears.
AB  - Tea has been shown to possess several health beneficial properties primarily due
      to its polyphenolic content. The major polyphenolic compounds in black tea leaves
      are theaflavins (TFs) formed by oxidative coupling of catechins in tea leaves
      during its processing. In this paper, we report the characterization of 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear inflammatory model and
      the inhibitory effects of major black tea TFs derivatives on this inflammation.
      In addition, the effect on inflammatory biomarkers, such as proinflammatory
      cytokines and arachidonic acid metabolites, are reported as well. A single
      topical application of TPA to ears of CD-1 mice induced a time- and dose
      dependent increase in edema as well as formation of proinflammatory cytokine
      proteins interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in mouse ears. A
      single topical application of equimolar of black tea constituents (TF, theaflavin
      3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate) strongly
      inhibited TPA-induced edema of mouse ears. Application of TFs mixture to mouse
      ears 20 min prior to each TPA application once a day for 4 days inhibited TPA
      induced persistent inflammation, as well as TPA-induced increase in IL-1beta and
      IL-6 protein levels. TFs also inhibited arachidonic acid (AA) metabolism via both
      cyclooxygenase (COX) and lipoxygenase pathways. This observation was
      substantiated by decreased amounts of AA metabolites prostaglandin E2 (PGE2) and
      leukotriene B4 (LTB4) levels. Combined application of TF and sulindac, a
      nonsteroidal anti-inflammatory drug resulted a significant synergetic anti
      inflammatory effect. Oral administration of TFs or the hot water extract of black
      tea leaves also significantly inhibited TPA-induced edema in mouse ears. In
      conclusion, proinflammatory cytokines, IL-1beta and IL-6, as well as the
      intermediated metabolites of AA, PGE2, and LTB4 are good biomarkers for
      inflammation. Black tea constituents, TF and its derivatives, had strongly anti
      inflammatory activity in vivo which may be due to their ability to inhibit AA
      metabolism via lipoxygenase and COX pathways.

PMID- 16404706
TI  - The role of tea and tea flavonoids in cardiovascular health.
AB  - Consumption of green or black tea has been inversely associated with the
      development and progression of cardiovascular diseases. In this review, the
      current knowledge about protective effects of tea and tea constituents,
      particularly flavonoids, on the cardiovascular system is summarized. Underlying
      mechanisms for the beneficial effects of tea include vasculoprotective,
      antioxidative, antithrombogenic, anti-inflammatory, and lipid-lowering properties
      of tea flavonoids. Although promising experimental data on beneficial effects of
      tea in various cardiovascular diseases are available, results of clinical studies
      in humans are not uniform. A number of factors are discussed which may contribute
      to inconsistent data in humans. Overall, tea represents a promising tool for the
      prevention and treatment of cardiovascular disorders.

PMID- 16404707
TI  - Opposing action of curcumin and green tea polyphenol in human keratinocytes.
AB  - Persistent environmental insult can convert a normal cell into a cancer cell.
      However, various natural chemopreventive agents called antioxidants can retard
      this progression. We have recently explored the effects of several
      chemopreventive agents, including green tea polyphenol and curcumin, on normal
      human keratinocyte function. Our findings suggest that a bioactive polyphenol
      from green tea, (-)-epigallocatechin-3-gallate (EGCG), acts to increase
      involucrin gene expression, suggesting that EGCG treatment enhances normal human
      keratinocyte differentiation. Mechanistic studies indicate that EGCG alters
      mitogen-activated protein kinase cascade function to activate involucrin gene
      transcription via a Ras, MEKK1, MEK3, ERK1/2-p38delta cascade that targets AP1
      and CAATT enhancer binding protein transcription factors. These findings suggest
      that EGCG may inhibit disease progression by promoting keratinocyte
      differentiation. Parallel studies indicate that not all antioxidants produce a
      similar response. Curcumin, an antioxidant derived from the turmeric, antagonizes
      the EGCG-dependent response by interfering in this signaling pathway. These
      studies suggest that different antioxidant may produce antagonistic effects in
      tissues.

PMID- 16404708
TI  - Mechanisms of hypolipidemic and anti-obesity effects of tea and tea polyphenols.
AB  - Among the health-promoting effects of tea and tea polyphenols, the cancer
      chemopreventive effects in various animal model systems have been intensively
      investigated; meanwhile, the hypolipidemic and antiobesity effects in animals and
      humans have also become a hot issue for molecular nutrition and food research. It
      has been demonstrated that the body weights of rats and their plasma
      triglyceride, cholesterol, and LDL-cholesterol have been significantly reduced by
      feedings of oolong, black, pu-erh, and green tea leaves to the animals. It has
      been suggested that the inhibition of growth and suppression of lipogenesis in
      MCF-7 breast cancer cells may be through down-regulation of fatty acid synthase
      gene expression in the nucleus and stimulation of cell energy expenditure in the
      mitochondria. The experimental data indicated that the molecular mechanisms of
      fatty acid synthase gene suppression by tea polyphenols (EGCG, theaflavins) may
      invite down-regulation of EGFR/PI3K/Akt/Sp-1 signal transduction pathways.

PMID- 16404709
TI  - No correlation between the clinical severity of autonomic symptoms (SCOPA-AUT)
      and electrophysiological test abnormalities in advanced Parkinson's disease.

PMID- 16404710
TI  - Ultrasound examination of the sigmoid colon: possible new diagnostic tool for
      irritable bowel syndrome.
AB  - OBJECTIVE: Irritable bowel syndrome (IBS) affects about 10% of the population,
      and is primarily a disease of women. It may cause chronic pelvic pain. As yet
      there is no imaging test to aid in diagnosis, which relies upon history. We aimed
      to determine whether transvaginal sonographic investigation of the sigmoid colon
      could aid in the diagnosis of IBS. METHOD: Transvaginal ultrasound was used in
      175 female patients undergoing pelvic ultrasound studies for a variety of
      reasons, none specifically for bowel complaints. We measured the wall of the
      sigmoid colon and then obtained the history of positive or negative for IBS.
      RESULTS: The majority of those 27 reporting a history of IBS had thickening of
      the wall of the sigmoid colon. A cut-off of 3.0 mm gave a sensitivity for this
      group of patients of 70%, specificity of 95%, positive predictive value of 73%
      and negative predictive value of 95%. CONCLUSION: Transvaginal ultrasound may be
      useful in identifying patients at risk for IBS. Consideration of colon wall
      measurement during pelvic ultrasound should be studied, as IBS may be a cause of
      chronic pelvic pain.

PMID- 16404711
TI  - Geometric morphometric analysis of shape outlines of the normal and abnormal
      fetal skull using three-dimensional sonographic multiplanar display.
AB  - OBJECTIVES: Geometric morphometric analysis has been used to quantify differences
      in biological shapes. Cranial irregularities are described in anomalous fetuses
      but are qualitative and ill-defined. Our goal was to apply geometric morphometric
      statistical analysis using three-dimensional (3D) multiplanar display to quantify
      shape differences in normal and abnormal fetal skulls. METHODS: This was a
      retrospective pilot study of mid-trimester patients undergoing ultrasonography.
      3D multiplanar display using spatial rotation was used to identify landmarks in
      coronal and transverse planes to establish a consistent fetal facial profile.
      Outline coordinates of the brow were determined by blinded examiners using
      computer software. Elliptical Fourier analysis (EFA) was used to obtain sets of
      functional coefficients. An atypicality index (AI) was determined from retained
      principal component (PC) scores. An AI > 95(th) percentile of the expected
      distribution defined outliers. RESULTS: Outlines were successfully identified in
      38 patients (six abnormal). Using the AI, there were three outliers, all from
      abnormal fetuses (trisomy 18, trisomy 21, and campomelic dysplasia). Two fetuses
      with trisomy 21 and one with an unbalanced translocation had normal atypicality
      indices. CONCLUSIONS: 3D multiplanar display and geometric morphometric analysis
      enable quantification of fetal skull shape. An abnormal skull shape was
      identified in two of four aneuploid fetuses and no normal ones. Geometric
      morphometric analysis represents a promising new quantitative modality which,
      when applied with 3D sonographic multiplanar display, may be used to more
      objectively analyze fetal malformation. Larger prospective trials are needed to
      refine the technique and improve reproducibility.

PMID- 16404712
TI  - Normal fetal lung volume measured with three-dimensional ultrasound.
AB  - OBJECTIVES: To construct reference intervals for fetal lung volumes measured
      longitudinally using three-dimensional (3D) ultrasound, and to evaluate the
      effect of gender on lung size. METHODS: This was a prospective, longitudinal
      study in the obstetric outpatient department of the VU University Medical Center,
      Amsterdam. Seventy-eight women with uncomplicated pregnancies were scanned three
      to four times at gestational ages of 18-34 weeks. 3D models of the lung were
      constructed using the ultrasound machine's software. After the infants were
      delivered the entire group was reanalyzed with regard to fetal gender. Centiles
      for the lung volumes of the entire group and for each gender separately were
      estimated using multilevel modeling. RESULTS: Charts and tables of right and left
      fetal lung volumes, using gestational age and estimated fetal weight as the
      independent variables, are presented. There was a significant difference in lung
      volume between male and female fetuses at each gestational age. Charts and tables
      of right and left fetal lung volumes for each gender at gestational ages of 18-34
      weeks are also presented. CONCLUSIONS: We present valid references for volumetric
      measurements of the right and left fetal lungs in male and female fetuses. The
      feasibility and reliability of fetal lung volume measurements using 3D ultrasound
      is good.

PMID- 16404713
TI  - Study of recombinant human osteogenic protein-1 expressed in prokaryocyte on the
      repair of extracted socket in rabbits.
AB  - The study investigated the effect of recombinant human osteogenic protein-1 (rhOP
      1) expressed in prokaryocyte, to promote the healing of alveolar socket. A model
      of rabbit extracted socket into which the composites of rhOP-1 and gelatin sponge
      was immediately implanted was created and the osteoinduction of rhOP-1 was
      assessed by histological method, quantitative measurement of calcium content and
      alkaline phosphatase (ALP) activity. The result of histology showed that bone
      healing in rhOP-1 side is 4-6 weeks earlier than that of the control side. ALP
      activity and calcium content in rhOP-1 side were significantly high compared with
      that of the control side. rhOP-1 has a satisfactory osteoinduction ability to
      promote the healing of extracted socket.

PMID- 16404714
TI  - A new biodegradable polyester elastomer for cartilage tissue engineering.
AB  - The objective of this study is to assess whether a new biodegradable elastomer,
      poly(1,8-octanediol citrate) (POC), would be a suitable material to engineer
      elastomeric scaffolds for cartilage tissue engineering. Porous POC scaffolds were
      prepared via the salt-leaching method and initially assessed for their ability to
      rapidly recover from compressive deformation (% recovery ratio). Controls
      consisted of scaffolds made from other materials commonly used in cartilage
      tissue engineering, including 2% agarose, 4% alginate, non woven poly(glycolic
      acid) (PGA) meshes, and non woven poly(L-lactide-co-glycolide) (PLGA) meshes.
      Articular chondrocytes from bovine knee were isolated and seeded onto porous disk
      shaped POC scaffolds, which were subsequently cultured in vitro for up to 28
      days. POC scaffolds completely recover from compressive deformation, and the
      stress-strain curve is typical of an elastomer (recovery ratio>98%). Agarose gel
      (2%) scaffolds broke during the compression test. The recovery ratio of 4%
      alginate gel scaffolds, PLLA, and PGA were 72, 85, and 88%, respectively. The
      Young's modulus of POC-chondrocyte constructs and cell-free POC scaffolds
      cultured for 28 days were 12.02+/-2.26 kPa and 3.27+/-0.72 kPa, respectively.
      After 28 days of culture, the recovery ratio of POC-chondrocyte constructs and
      cell-free POC scaffolds were 93% and 99%, respectively. The glycosaminoglycan
      (GAG) and collagen content at day 28 was 36% and 26% of that found in bovine knee
      cartilage explants. Histology/immunohistochemistry evaluations confirm that
      chondrocytes were able to attach to the pore walls within the scaffold, maintain
      cell phenotype, and form a cartilaginous tissue during the 28 days of culture.

PMID- 16404715
TI  - Release kinetics of ampicillin, characterization and bioactivity of TiO2/PCL
      hybrid materials synthesized by sol-gel processing.
AB  - Poly(epsilon-caprolactone) (PCL 6, 12, and 24 wt %) and titanium (TiO2) organic
      inorganic hybrid materials have been synthesized by the sol-gel method from a
      multicomponent solution containing titanium butoxide, poly(epsilon-caprolactone)
      (PCL), water, and chloroform (CHCl3). Sodium ampicillin was incorporated in the
      hybrid material to verify the effect as local controlled drug delivery system.
      The structure of a hybrid materials interpenetrating network is realized by
      hydrogen bonds between Ti-OH group (H-donator) in the sol-gel intermediate
      species and carboxylic group (H-acceptor) in the repeating units of the polymer.
      The presence of hydrogen bonds between organic/inorganic components of the hybrid
      materials was proved by FTIR analysis. The morphology of the hybrid materials was
      studied by scanning electron microscope (SEM). The structure of a molecular level
      dispersion has been disclosed by atomic force microscope (AFM), pore size
      distribution and surface measurements. The bioactivity of the synthesized hybrid
      materials has been showed by the formation of a layer of hydroxyapatite on the
      surface of TiO2/PCL samples soaked in a fluid simulating the composition of the
      human blood plasma. The amount of sodium ampicillin released has been detected by
      UV-vis spectroscopy and SEM. The release kinetics seems to occur in more than one
      stage. HPLC analysis has also been taken to ensure the integrity of ampicillin
      after the synthetic treatment.

PMID- 16404716
TI  - Alternative chaperone machinery may compensate for calreticulin/calnexin
      deficiency in Caenorhabditis elegans.
AB  - Proper folding and maintenance of the native structure are central to protein
      function and are assisted by a family of proteins called chaperones. Calreticulin
      and calnexin are ER resident chaperones well conserved from worm to human.
      Calreticulin/calnexin knock-out mice exhibit a severe phenotype, whereas in
      Caenorhabditis elegans, calreticulin [crt-1(jh101)]- and calnexin [cnx-1(nr2009)]
      null mutant worms exhibit only a mild phenotype, suggesting the possible
      existence of alternative chaperone machinery that can compensate for the
      deficiency of calreticulin and/or calnexin. In order to rapidly identify the
      compensatory chaperone components involved in this process, we analyzed the
      proteome of crt-1(jh101) mutants and [crt-1(jh101);cnx-1(nr2009)] double mutants.
      When grown at 20 degrees C, we found that five proteins were up-regulated and two
      proteins were down-regulated in crt-1(jh101) mutants; nine proteins were up
      regulated and five proteins were down-regulated in [crt-1(jh101);cnx-1(nr2009)]
      double mutants. In addition, elevation of the cultivation temperature to 25
      degrees C, which is still permissive to growth but causes specific defects in
      mutants, led to the identification of several additional proteins. Interestingly,
      the consistent increment of heat shock protein-70 family members (hsp70) together
      with protein disulfide isomerase (PDI) at all the examined conditions suggests
      the possible compensatory function imparted by hsp70 and PDI family members in
      the absence of calreticulin and/or calnexin.

PMID- 16404717
TI  - Profiling of differential protein expression in angiogenin-induced HUVECs using
      antibody-arrayed ProteoChip.
AB  - ProteoChip has been developed as a novel protein microarray technology. So far it
      has been applied in new lead screening and molecular diagnostics and we expect
      its role to grow in the field of biology. Here, we investigated the application
      of ProteoChip for the study of differential protein expression profiles in
      angiogenin-induced human umbilical vein endothelial cells (HUVECs). Antibody
      microarrays constructed by immobilizing 60 distinct antibodies against signal
      transducing proteins on ProteoChip base plates were used to analyze the
      expression pattern of cell-signaling proteins in HUVECs treated with angiogenin.
      The antibody microarray approach showed that angiogenin induced the up- and down
      regulation of several cellular regulators related with cell proliferation.
      Changes in the expression of signaling proteins determined by antibody microarray
      were validated by Western blot analysis. In this experiment, ten up-regulated
      proteins and six down-regulated proteins were identified and confirmed by
      immunoblot analysis. Taken together, these data suggest that antibody microarrays
      using ProteoChip technology can be a powerful tool for high-throughput analysis
      of proteomes in biological samples.

PMID- 16404718
TI  - Identification of immunodominant excretory-secretory cysteine proteases of adult
      Paragonimus westermani by proteome analysis.
AB  - Paragonimus westermani causes inflammatory lung disease in humans. The parasite
      excretes a host of biologically active molecules, which are thought to be
      involved in pathophysiological and immunological events during infection.
      Analyses of the 2-DE protein profiles of the excretory-secretory products (ESP)
      of adult P. westermani revealed approximately 147 protein spots, at least 15 of
      which were identified as cysteine proteases (CPs), at pHs between 4.5 and 8.5,
      and molecular weights (MWs) between 27 and 35 kDa. An additional three CPs
      (designated as PwCP-3, -8 and -11) were newly recognized by TOF/TOF MS. Their
      molecular biological information, which shared a high level sequence homology,
      was elucidated. The majority of the CPs reacted strongly with sera from
      paragonimiasis patients. When we observed the chronological changes in the
      antibody responses of the respective CPs against canine sera collected serially
      at 1, 3, 5, 7, 11 and 14 wk after experimental infection, these molecules
      exhibited a multiplicity of distinct immune recognition patterns. Our results
      clearly showed that P. westermani adult ESP were principally composed of
      excretory-secretory CPs, and that these CPs may exert effects not only on host
      tissue degradation and nutrient uptake, but also on the immune-regulating cells
      via synergistic and independent interactions.

PMID- 16404719
TI  - Identification of target proteins of N-acetylglucosaminyl transferase V in human
      colon cancer and implications of protein tyrosine phosphatase kappa in enhanced
      cancer cell migration.
AB  - To gain a better understanding of the mechanism underlying colon cancer and to
      search for potential markers of colon cancer prognosis, a comparative proteomic
      analysis of colon cancer WiDr cells was conducted using 2-DE and lectin blot,
      followed by identification based on ESI-MS. Through these approaches 14 proteins
      were identified as candidate target proteins for N-acetylglucosaminyl transferase
      V (GnT-V) that would be expected to be implicated in the progression of colon
      cancer. We selected protein tyrosine phosphatase kappa (PTPkappa) as a model
      protein to validate this approach to the discovery of novel biomarkers in colon
      cancer. PTPkappa underwent an aberrant glycosylation in GnT-V-overexpressing WiDr
      cells, and the aberrantly glycosylated PTPkappa was vulnerable to proteolytic
      cleavage. The enhanced cleavage of PTPkappa in GnT-V-overexpressing cells was
      responsible for the mitigation of the homophilic binding capacity, resulting in
      an increase in cancer cell migration.

PMID- 16404720
TI  - Proteomic analysis of mammalian basic proteins by liquid-based two-dimensional
      column chromatography.
AB  - To develop a standard method for separating highly basic proteins in mammalian
      cells, we established a 2-D LC separation system coupled with
      chromatofocusing/nonporous RP column chromatography (CF/NPRPC) in a ProteomeLab
      PF2D system. After standardizing conditions for 2-D LC, a 2-D liquid protein map
      of uninfected macrophage proteins with pH range 8.3-11.3 was constructed, and
      then compared with a macrophage protein map made after infection with Candida
      albicans. The results demonstrate that 2-D LC offers both high resolution and
      reproducibility for separation of highly basic, macrophage proteins. After
      protein identification using a nano 2-D LC-MS/MS Proteomics Solution System,
      quantitative determination of the changes in the differentially expressed
      proteins (e.g., galectin-3) in C. albicans-infected macrophages was also
      accomplished by measuring the peak area of the chromatogram in 2-D LC. The result
      from this measurement of galectin-3 expression shows a 3.41-fold decrease in the
      infected macrophage cells, which was further confirmed by that from the RT-PCR of
      mRNA of galectin-3. Thus, 2-D LC coupled with CF/NPRPC could be applicable to
      common analysis of highly basic proteins in a high-throughput manner.

PMID- 16404721
TI  - Protein microarrays on hybrid polymeric thin films prepared by self-assembly of
      polyelectrolytes for multiple-protein immunoassays.
AB  - We report here the development and characterization of protein microarrays
      fabricated on nanoengineered 3-D polyelectrolyte thin films (PET) deposited on
      glass slide by consecutive adsorption of polyelectrolytes via self-assembly
      technique. Antibodies or antigens were immobilized in the PET-coated glass slides
      by electrostatic adsorption and entrapment of porous structure of the 3-D polymer
      film and thus establishing a platform for parallel analysis. Both antigen and
      antibody microarrays were fabricated on the PET-coated slides, and direct and
      indirect immunoassays on protein microarrays for multiple-analyte detection were
      demonstrated. Microarrays produced on these PET-coated slides have consistent
      spot morphology and provide performance features needed for proteomic analysis.
      The protein microarrays on the PET films provide LOD as low as 6 pg/mL and
      dynamic ranges up to three orders of magnitude, which are wider than the protein
      microarrays fabricated on aldehyde and poly-L-lysine functionalized slides. The
      PET films constructed by self-assembly technique in aqueous solution is green
      chemistry based, cost-effective method to generate 3-D thin film coatings on
      glass surface, and the coated slide is well suited for immobilizing many types of
      biological molecules so that a wide variety of microarray formats can be
      developed on this type of slide.

PMID- 16404723
TI  - Identification of S-nitrosylated proteins after chronic exposure of colon
      epithelial cells to deoxycholate.
AB  - Apoptosis resistance, a condition favoring genomic instability, is associated
      with higher risk of colorectal cancer. Deoxycholate (DOC) is a hydrophobic bile
      salt found in high concentrations in colon cancer patients, and induces apoptosis
      in cultured colonic cells and ex vivo in colonic biopsies. We showed previously
      that the chronic exposure of colon cancer cells to increasing concentrations of
      DOC leads to apoptosis resistance, and the suggested mechanism involves
      oxidative/nitrosative stress. Nitric oxide (NO) is a key signaling molecule that
      regulates cell function in a variety of physiologic and pathophysiologic states.
      In part, NO exerts its actions by S-nitrosylation of target thiols, and several
      proteins are regulated through this PTM, including the caspases, the main
      effectors of apoptosis. Here, we performed a proteomics study in the DOC-induced
      apoptosis-resistant colon cell line, HCT-116RC. Its profile of S-nitrosylated
      proteins was compared to a control cell line not exposed to DOC. Eighteen
      differentially S-nitrosylated proteins were identified in the HCT-116RC cell
      line, 14 of these are novel targets of S-nitrosylation not previously reported.
      These proteins include cytoskeletal and signaling proteins, metabolic enzymes,
      chaperones, and redox- and differentiation-related proteins. These results
      broaden our knowledge of potential signal transduction pathways that may lead to
      the development of new biomarkers and therapy targets.

PMID- 16404722
TI  - Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS.
AB  - Tetraspanins are integral membrane proteins involved in a variety of
      physiological and pathological processes. In cancer, clinical and experimental
      studies have reported a link between tetraspanin expression levels and
      metastasis. Tetraspanins play a role as organizers of a molecular network of
      interactions, the "tetraspanin web". Here, we have performed a proteomic
      characterization of the tetraspanin web using a model of human colon cancer
      consisting of two cell lines derived from primary tumor and metastasis from the
      same patient. The tetraspanin complexes were isolated after immunoaffinity
      purification and the proteins were identified by MS using LC-ESI-MS/MS and MALDI
      FTICR. The high resolution and mass accuracy of FTICR MS allowed reliable
      identification using mass finger printing with only two peptides. Thus, it could
      be used to resolve the composition of complex peptide mixtures from membrane
      proteins. Different types of membrane proteins were identified, including
      adhesion molecules (integrins, Lu/B-CAM, GA733 proteins), receptors and signaling
      molecules (BAI2, PKC, G proteins), proteases (ADAM10, TADG15), and membrane
      fusion proteins (syntaxins) as well as poorly characterized proteins (CDCP1, HEM
      1, CTL1, and CTL2). Some components were differentially detected in the
      tetraspanin web of the two cell lines. These differences may be relevant for
      tumor progression and metastasis.

PMID- 16404725
TI  - Comparative proteomic analysis of Helicobacter pylori strains associated with
      iron deficiency anemia.
AB  - Helicobacter pylori is known to cause chronic gastritis, peptic ulcer, and
      gastric cancer, and has also been linked to iron deficiency anemia (IDA). To
      determine whether H. pylori clinical isolates correlate with the prevalence of H.
      pylori-associated IDA, we compared the proteomic profiles of H. pylori strains
      isolated from antral biopsy specimens of H. pylori-positive patients with or
      without IDA. Fifteen strains, including eight non-IDA and seven IDA strains, were
      cultured under iron-rich and iron-depleted conditions and then analyzed for
      protein expression profiles by 2-DE. The distances between two H. pylori strains
      were determined on the basis of similarities between their expression patterns of
      189 protein spots, and a phylogenetic tree was constructed. The results revealed
      that the IDA strains formed a cluster separate from that of six non-IDA strains,
      with two non-IDA strains between the clusters. H. pylori strain 26695 was located
      in the non-IDA cluster. Protein spots displaying similar expression patterns were
      clustered, and 18 spots predominantly expressed in IDA strains were identified by
      MALDI-TOF analysis. These data indicate that the non-IDA and IDA strains can be
      distinguished by their protein expression profiles, suggesting that the
      polymorphism of H. pylori strains may be one of the factors determining the
      occurrence of H. pylori-associated IDA.

PMID- 16404724
TI  - Searching for aging-related proteins in human dermal microvascular endothelial
      cells treated with anti-aging agents.
AB  - Endothelial cells constitute an interface between blood and tissue and act as a
      medium for active interaction between plasma and the intracellular environment
      for homeostasis. Aging of endothelial cells plays a significant role in the
      pathophysiology of age-related vascular diseases; however, precise mechanisms for
      senescence have not been elucidated. Proteomics allows identification of protein
      structures, functions, and characteristics, and can be applied to the study of
      aging processes. Using cultured human dermal microvascular endothelial cells and
      two-dimensional proteomic mapping, we studied the effects of kinetin,
      epigallocatechin-3-gallate, all-trans-retinoic acid, and selenium on their
      senescence and searched for the aging-related proteins. The treatments resulted
      in 68 qualitative changes and 172 quantitative changes, and we were able to
      identify 46 spots among them. All of the agents indicated above induced changes
      in the expression of moesin, rho guanosine-5'-diphosphate-dissociation inhibitor,
      and actin, confirmed by immunoblotting and confocal laser microscopy. As these
      proteins were associated with cell cycle and cytoskeleton, immunoblotting of the
      proteins related to cell cycle was performed. Although practical significance
      remains to be confirmed by in vivo research, this fundamental discovery may
      provide a basis for understanding the mechanism of aging and age-related
      diseases.

PMID- 16404726
TI  - Mass spectrometric sequencing of endotoxin proteins of Bacillus thuringiensis
      ssp. konkukian extracted from polyacrylamide gels.
AB  - The amino acid sequences of the crystal proteins of Bacillus thuringiensis ssp.
      konkukian strain HL-47 are unknown. We used 1-D denaturing polyacrylamide
      electrophoresis, nano-ESI-Q-TOF-MS, and protein database searching to analyze
      these proteins. On SDS-PAGE gels, a preparation of purified crystal proteins
      exhibited 110, 102, 76, 55, 37, and 30 kDa protein bands. Immunoblotting of the
      gel with antiserum raised to this preparation revealed that four crystal
      proteins, of 110, 102, 55, and 37 kDa, reacted with the specific antiserum. The
      102-kDa major protein reacted strongly. The other crystal proteins showed weak
      immunoreactivity. The 102 and 55 kDa proteins were analyzed by ESI-MS. The
      internal amino acid sequence of the 102-kDa major protein has similarity to the
      sequences of the surface layer protein of B. thuringiensis ssp. finitimus and B.
      anthracis. However, the internal amino acid sequences of the 55 kDa protein did
      not show any homology to proteins in the databases. Proteomic analysis of these
      proteins leads to the conclusion that the sequence data provided the protein
      databases of the crystal proteins of the konkukian ssp.

PMID- 16404727
TI  - Quantitative ASL muscle perfusion imaging using a FAIR-TrueFISP technique at 3.0
      T.
AB  - The feasibility of muscle perfusion imaging with diagnostic image quality was
      demonstrated using the FAIR-TrueFISP arterial spin labeling technique on a
      clinical 3.0 T whole-body scanner. In eight healthy volunteers (24 to 42 years
      old), quantitative perfusion maps of the forearm musculature were acquired before
      and after intense exercise. All measurements were carried out in a 3.0 T whole
      body MR unit in combination with an eight-channel head coil. Pulsed arterial spin
      labeling and data recording were performed with an adapted FAIR-TrueFISP
      technique and quantitative perfusion maps were calculated on a pixel-by-pixel
      basis by means of the extended Bloch equations. Perfusion images with an in-plane
      resolution of 1 mm showed no significant distortions or blurring. Perfusion-time
      curves could be recorded with a temporal resolution of 6.4 s. Maximum perfusion
      in the musculature was found approximately 2 min after exercise, reaching values
      of up to 220 mL/min per 100 g of tissue with good delineation between the active
      muscles and the musculature not involved in the exercise. In conclusion, the
      TrueFISP pulsed arterial spin labeling technique allows patient-friendly
      assessment of muscular perfusion in a clinical whole-body scanner.

PMID- 16404728
TI  - Non-invasive temperature imaging with thulium 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetramethyl-1,4,7,10-tetraacetic acid (TmDOTMA-).
AB  - Non-invasive thermometry using hyperfine-shifted MR signals from paramagnetic
      lanthanide complexes has attracted attention recently because the chemical shifts
      of these complexes are many times more sensitive to temperature than the water 1H
      signal. Among all the lanthanide complexes examined thus far, thulium tetramethyl
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTMA-) appears to be the
      most suitable for MR thermometry. In this paper, the feasibility of imaging the
      methyl 1H signal from TmDOTMA- using a frequency-selective radiofrequency
      excitation pulse and chemical shift-selective (CHESS) water suppression is
      demonstrated. A temperature imaging method using a phase-sensitive spin-echo
      imaging sequence was validated in phantom experiments. A comparison of regional
      temperature changes measured with fiber-optic probes and the temperatures
      calculated from the phase shift near each probe showed that the accuracy of
      imaging the temperature with TmDOTMA- is at least 0.1-0.2 degrees C. The
      feasibility of imaging temperature changes in an intact rat at 0.5-0.6 mmol/kg
      dose in only a few minutes is demonstrated. Similar to commonly used MRI contrast
      agents, the lanthanide complex does not cross the blood-brain barrier. TmDOTMA-
      may prove useful for temperature imaging in many biomedical applications but
      further studies relating to acceptable dose and signal-to-noise ratio are
      necessary before clinical applications.

PMID- 16404730
TI  - Open access.

PMID- 16404729
TI  - Hemodynamic effects of clonidine in two contrasting models of autonomic failure:
      multiple system atrophy and pure autonomic failure.
AB  - We assessed the effects of clonidine on blood pressure (BP) and heart rate (HR)
      in multiple system atrophy (MSA), where the autonomic nervous system lesion site
      is preganglionic, and in pure autonomic failure (PAF), where it is
      postganglionic. In normal subjects, intravenous infusion of the selective alpha2
      adrenoceptor agonist clonidine reduces BP and plasma noradrenaline (NA) levels by
      means of central alpha2-adrenoceptor action, as well as inducing growth hormone
      (GH) release. Clonidine-induced GH release is impaired in MSA but spared in PAF.
      However, the hemodynamic effects of clonidine have not been studied extensively
      in these disorders. We examined intravenous clonidine test results (performed in
      our autonomic laboratories using the London Autonomic Units protocol) in 58
      patients: 39 with probable MSA and 19 with PAF. Systolic BP (SBP), diastolic BP
      (DBP), HR, and NA levels were measured supine at baseline and for up to 60
      minutes after clonidine. Clonidine resulted in a significant BP fall in MSA
      patients, which occurred earlier (within 15 minutes of clonidine) and to a
      greater extent than seen in PAF patients. MSA and PAF patients showed reduction
      in HR after clonidine administration, although this finding was significantly
      greater in MSA than in PAF patients. NA levels decreased significantly after
      clonidine administration in both groups. Although basal NA levels were lower in
      PAF than in MSA patients, there was no difference in NA reduction relative to
      baseline between groups. MSA patients showed significant negative correlation
      between basal NA levels and BP response to clonidine. Clonidine infusion reduces
      BP and HR in both MSA and PAF groups but to a greater extent in MSA patients. The
      greater vasodepressor action of clonidine in MSA patients suggests that there is
      partial preservation of brainstem sympathetic outflow pathways in MSA and may
      reflect its action at sites in the brainstem and spinal cord that were in part
      functionally preserved in MSA. Despite similar degrees of NA reduction after
      clonidine administration, the vasodepressor effect of clonidine was attenuated in
      PAF compared with MSA patients. This attenuation in PAF patients may reflect
      greater peripheral alpha2-adrenoceptor denervation supersensitivity due to the
      postganglionic lesion site. These BP differences, thus, may reflect the
      underlying lesion site in MSA and PAF, and the hemodynamic data after clonidine
      infusion may help differentiate these conditions.

PMID- 16404732
TI  - Testing a model of symptoms, communication, uncertainty, and well-being, in older
      breast cancer survivors.
AB  - Among older, long-term breast cancer survivors, symptoms from previous treatment
      can generate uncertainty about whether they represent co-morbid conditions,
      recurrence, or normal aging. This uncertainty can result in emotional distress
      and thoughts of recurrence. Communication with health care providers may help
      women reduce uncertainty and improve both emotional and cognitive well-being. To
      assess the influence of symptoms, uncertainty, and communication with providers
      on well-being, data from 203 Caucasian and African American survivors, 5-9 years
      post treatment, were tested using structural equation modeling. Symptoms, age,
      and uncertainty had the strongest influence on well-being, regardless of race.
      There was an unexpected positive association between patient-provider
      communication and thoughts of recurrence. Descriptive analysis revealed that 52%
      of women were unable to achieve their desired decision-making role with health
      care providers.

PMID- 16404731
TI  - Comparison of the original and revised structures of the Health Promotion Model
      in predicting construction workers' use of hearing protection.
AB  - Pender's health promotion model (HPM) has been revised, including substantial
      changes in its structure. The purpose of this study was to compare the fit and
      predictive usefulness of the original and revised structures of the HPM as
      applied to the use of hearing protection devices by 703 construction workers.
      Structural equation modeling was used to evaluate the two alternative forms of
      the model. Both forms of the model fit well, with the revised structure having a
      better fit and explaining more of the variance in use of hearing protection (28%
      vs. 18%). Results support the revised structure of the health promotion model
      (HPM) over the original form, and indicate it may be useful in understanding and
      predicting use of hearing protection.

PMID- 16404734
TI  - Development and psychometric testing of The Care in Obstetrics: Measure for
      Testing Satisfaction (COMFORTS) scale.
AB  - This paper describes the development and psychometric assessment of a scale to
      measure satisfaction with intrapartum and postpartum care in hospital: The Care
      in Obstetrics: A Measure For Testing Satisfaction (COMFORTS) scale. A sample of
      415 participants completed the 40-item scale. Cronbach's alpha for the scale was
      .95. Evaluation of construct validity through principal components factor
      analysis with varimax rotation yielded six subscales: confidence in newborn care,
      postpartum nursing care, provision of choice, the physical environment, respect
      for privacy, and labor/delivery nursing care. The COMFORTS scale was able to
      discriminate between multiparous versus primiparous women, and between women
      cared for in single room maternity care versus in separate labor/delivery and
      postpartum rooms. Pending further validation, the COMFORTS scale has potential to
      measure women's satisfaction with childbirth care and contribute to an assessment
      of the quality of care provided.

PMID- 16404733
TI  - Fatigue and associated factors in hemodialysis patients in Taiwan.
AB  - The number of patients suffering from end-stage renal disease is increasing
      rapidly around the world, including in Taiwan. Hemodialysis (HD) patients report
      fatigue as a major stressor. The purpose of this correlational study with
      systematic sampling was to explore fatigue and associated physiological,
      psychological, and situational factors in 119 Taiwanese HD patients. Results
      indicate that levels of fatigue were mild. Three variables (gender, employment,
      and depression) had a significant impact on fatigue. Some differences in
      physiological factors by depression, gender, and employment were found. Stepwise
      regressions showed that depression, age, and urea reduction ratio were
      significant predictors for overall fatigue and two of its dimensions. Some
      relationships from the theory of unpleasant symptoms were supported.

PMID- 16404735
TI  - Relationship between nursing interventions and outcome achievement in acute care
      settings.
AB  - The extent to which nursing interventions provided during hospitalization are
      associated with patients' therapeutic self-care and functional health outcomes
      was explored with a voluntary sample of 574 patients. Nurses collected data on
      patient outcomes at admission and discharge using the minimum data set (MDS) and
      the therapeutic self-care scale (TSCS). Research assistants audited charts for
      documentation of nursing interventions. The results indicated that nursing
      interventions aimed at exercise promotion, positioning, and self-care assistance
      predicted functional status outcome. Higher functional status outcome predicted
      therapeutic self-care ability at hospital discharge. The results demonstrate that
      nurses can use MDS and TSCS data on patient outcomes to gain insight into the
      effectiveness of their interventions.

PMID- 16404736
TI  - Common deactivation patterns during working memory and visual attention tasks: an
      intra-subject fMRI study at 4 Tesla.
AB  - This parametric functional magnetic resonance imaging (fMRI) study investigates
      the balance of negative and positive fMRI signals in the brain. A set of visual
      attention (VA) and working memory (WM) tasks with graded levels of difficulty was
      used to deactivate separate but overlapping networks that include the frontal,
      temporal, occipital, and limbic lobes; regions commonly associated with auditory
      and emotional processing. Brain activation (% signal change and volume) was
      larger for VA tasks than for WM tasks, but deactivation was larger for WM tasks.
      Load-related increases of blood oxygenation level-dependent (BOLD) responses for
      different levels of task difficulty cross-correlated strongly in the deactivated
      network during VA but less so during WM. The variability of the deactivated
      network across different cognitive tasks supports the hypothesis that global
      cerebral blood flow vary across different tasks, but not between different levels
      of task difficulty of the same task. The task-dependent balance of activation and
      deactivation might allow maximization of resources for the activated network.

PMID- 16404737
TI  - Functional conservatism in mitochondrial evolution: insight from hybridization of
      arctic and brook charrs.
AB  - To assess the potential adaptive value of mtDNA, we evaluated functional
      properties and thermal sensitivity of key mitochondrial enzymes in two species
      that have originally evolved in different thermal environments (arctic charr,
      Salvelinus alpinus, and brook charr, S. fontinalis), as well as in their hybrids.
      We measured the activity of two enzymes of the electron transport system
      (cytochrome c oxidase and NADH-ubiquinone oxidoreductase), one enzyme of the
      mitochondrial matrix (citrate synthase), and one enzyme of the anaerobic
      glycolysis (lactate dehydrogenase) in the red muscle at three temperatures (6
      degrees C, 12 degrees C and 18 degrees C). Surprisingly, the species presented no
      significant differences in enzyme activity, thermal sensitivity or
      thermostability of key metabolic enzymes even though they evolved in different
      thermal environments and present important differences in amino acid sequences.
      It seems that amino acid substitutions between those species have minor impact on
      the functional properties of mitochondrial enzymes studied. The thermal
      sensitivity results (Q(10)) obtained for inner-membrane mitochondrial enzymes
      differed somewhat from those of mitochondrial matrix or cytosolic enzymes. This
      result indicates the modulation of thermal sensitivity of all mitochondrial inner
      membrane processes by a common parameter, which could be the structural and
      functional properties of membrane phospholipids.

PMID- 16404738
TI  - The global health burden of infection-associated cancers in the year 2002.
AB  - Several infectious agents are considered to be causes of cancer in humans. The
      fraction of the different types of cancer, and of all cancers worldwide and in
      different regions, has been estimated using several methods; primarily by
      reviewing the evidence for the strength of the association (relative risk) and
      the prevalence of infection in different world areas. The estimated total of
      infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of
      the global cancer burden. The principal agents are the bacterium Helicobacter
      pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B
      and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV)
      together with the human herpes virus 8 (0.9%). Relatively less important causes
      of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I
      (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in
      developing countries (1.5 million cases per year) and 7.7% in developed countries
      (390,000 cases) if these infectious diseases were prevented. The attributable
      fraction at the specific sites varies from 100% of cervix cancers attributable to
      the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide)
      caused by liver flukes.

PMID- 16404739
TI  - Periventricular leukomalacia specifically affects cortical MEG response to
      biological motion.
AB  - OBJECTIVE: Periventricular leukomalacia (PVL) underlies most of the neurological
      morbidity including visual-perceptual deficits in survivors of premature birth.
      However, it is unknown whether and, if so, how PVL affects functional cortical
      activity. METHODS: Here, we assessed changes in the magnetoencephalographic (MEG)
      response to visual displays depicting human locomotion in adolescents who were
      born premature with magnetic resonance imaging signs of PVL. RESULTS: Dynamics of
      MEG activity parallel behavioral deficits. Early (140-170 milliseconds) brain
      activation over the right parietal cortex was weaker in patients compared with
      term-born controls. INTERPRETATION: This is the first evidence for stimulus
      specific modulation of cortical activity by periventricular lesions providing new
      insights into the functional pathology of PVL.

PMID- 16404740
TI  - Acute and delayed nausea and emesis control in pediatric oncology patients.
AB  - BACKGROUND: To the authors' knowledge there is little information available
      regarding the effectiveness of standard antiemetic therapy among cancer patients
      who receive emetogenic chemotherapy in clinical practice, especially in the
      pediatric population. The current study was undertaken to determine the
      effectiveness of standard antiemetic interventions among children receiving
      emetogenic chemotherapy. METHODS: The authors conducted a retrospective review of
      antiemetic surveys for children who received emetogenic chemotherapy. Patients
      and/or their parents were surveyed for acute and delayed nausea and emesis after
      each course of emetogenic chemotherapy. The survey consisted of validated
      measures of the severity of nausea and emesis. Complete protection (CP) rates
      were calculated for each chemotherapy regimen during both the acute and delayed
      phases and also by gender and age group (ages birth-3 yrs, 4-11 yrs, and 12-20
      yrs). Antiemetic therapy consisted of intravenous ondansetron administered once
      daily during chemotherapy either alone (for moderately emetogenic chemotherapy)
      or in combination with dexamethasone (for severely emetogenic chemotherapy).
      RESULTS: In total, 224 different patients completed 1256 surveys. CP from both
      acute and delayed nausea and emesis was more likely in the children ages birth-3
      years than in older children. For moderately emetogenic regimens, nausea and
      emesis in the acute and delayed phases were controlled well. Among severely
      emetogenic chemotherapy regimens, 7 of 12 different regimen types had CP rates <
      50% in either the acute phase or the delayed phase. CP rates were particularly
      low for cisplatin-based and cyclophosphamide-based regimens. CONCLUSIONS: Nausea
      and emesis remain significant problems among children who receive emetogenic
      chemotherapy. CP rates were associated significantly with patient age, and higher
      rates were observed among very young children.

PMID- 16404741
TI  - Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide
      significant reduction in toxicity compared with doxorubicin, vincristine, and
      dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III
      multicenter randomized trial.
AB  - BACKGROUND: Pegylated liposomal doxorubicin has pharmacologic and safety
      advantages over conventional doxorubicin. METHODS: For this noninferiority trial,
      192 patients with newly diagnosed, active multiple myeloma were randomized to
      receive either combined pegylated liposomal doxorubicin (40 mg/m(2)) and
      vincristine (1.4 mg/m(2); maximum, 2.0 mg) as an intravenous infusion on Day 1
      plus reduced-dose dexamethasone (40 mg) orally on Days 1-4 (DVd) (n = 97
      patients) or combined vincristine (0.4 mg per day) and conventional doxorubicin
      (9 mg/m(2) per day) as a continuous intravenous infusion on Days 1-4 plus reduced
      dose dexamethasone (VAd) (n = 95 patients) for at least 4 cycles. Treatment was
      repeated every 4 weeks until patients either achieved maximal response, disease
      progression, or unacceptable toxicity or underwent transplantation. The primary
      endpoints were response and toxicity. RESULTS: Objective response rates (DVd,
      44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and
      overall survival (hazard ratio, 0.88; P = 0.67) were similar between the
      treatment groups. However, DVd was associated with significantly less Grade 3/4
      neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), a lower incidence of
      sepsis, and less antibiotic use. Compared with VAd, DVd also significantly
      decreased the need for central venous access (P < 0.0001) and growth-factor
      support (P = 0.03) and resulted in less alopecia (20% vs. 44%; P < 0.001) but
      more hand-foot syndrome (25% vs. 1%; P < 0.001), mainly Grade 1/2. CONCLUSIONS:
      The DVd regimen demonstrated similar efficacy with less toxicity and supportive
      care compared with VAd, which should improve clinical utility and optimize the
      opportunity for transplantation.

PMID- 16404743
TI  - Functional connectivity networks are disrupted in left temporal lobe epilepsy.
AB  - OBJECTIVE: Functional connectivity maps the distributed network of brain regions
      fluctuating synchronously during a continuous brain state. This study sought to
      investigate whether patients with left temporal lobe epilepsy (TLE) differ from
      controls in their resting-state functional connectivity between typical language
      regions. METHODS: We studied 17 patients with left TLE, together with eight
      healthy controls, using seeded functional connectivity. Seed regions were defined
      using the regions of maximal activation and deactivation during a language
      functional magnetic resonance imaging (fMRI) task in a separate cohort of 30
      controls. RESULTS: Language fMRI produced the expected activation pattern, which
      was not different between patients and controls. However, functional connectivity
      between language areas during rest was markedly different; whereas controls
      showed connectivity between each of the seed areas and the majority of the
      language areas, patients showed connectivity only with a few areas, particularly
      the seed area itself. This difference was significant in the direct comparison of
      patients and control connectivity maps. INTERPRETATION: We suggest that this
      reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of
      the language network during resting state in patients and may be related to
      subtle language difficulties in this patient population.

PMID- 16404742
TI  - Enhanced viral and tumor immunity with intranodal injection of canary pox viruses
      expressing the melanoma antigen, gp100.
AB  - BACKGROUND: The route of administration and extent of helper T-cell activation
      are factors that are likely to be important for the development of effective
      cancer vaccines. In order to optimize CD8(+) cytotoxic T-lymphocyte (CTL)
      responses, the immunologic effects of direct lymph node (LN) injections of canary
      pox virus (ALVAC) vectors (expressing the melanoma antigen, gp100) and
      immunogenic gp100 peptides, along with concomitant injections of the helper
      adjuvant, tetanus toxoid, were studied in high-risk HLA-A*0201(+) patients.
      METHODS: Forty-two patients were vaccinated using six different protocols. Twenty
      three patients were 'primed' with ALVAC(2)-gp100m and 'boosted' with gp100
      peptides, either subcutaneously or into an LN. Intranodal (IN) peptides, alone,
      were administered to six patients. Thirteen patients were given tetanus toxoid
      initially, and with each gp100 vaccination. Toxicity was recorded and immunologic
      responses were determined in 35 patients by enzyme-linked immunospot (ELISPOT)
      and gp100-tetramer binding assays and anti-ALVAC(2) enzyme-linked immunosorbent
      assays (ELISAs). RESULTS: All vaccine protocols were tolerated well. Using
      stringent criteria for immunologic response, 8 of 18 patients responded to the
      viral vaccines, in striking contrast to peptides only (0 of 6 patients) or with
      help in trans from tetanus-reactive T-cells (1 of 11 patients). Changes in gp100
      reactive CTL frequencies and ALVAC antibodies were greatest when viruses were
      injected directly into LNs. CONCLUSIONS: IN injections of ALVAC(2)-gp100m viruses
      are feasible, safe, and may be a superior method of vaccination in humans. CTL
      responses to this vaccine were not enhanced by tetanus toxoid.

PMID- 16404744
TI  - K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without
      mixed-lineage leukemia gene rearrangements.
AB  - BACKGROUND: It is believed that Ras mutations drive the proliferation of leukemic
      cells. The objective of this study was to investigate the association of Ras
      mutations with childhood acute lymphoblastic leukemia (ALL) and acute myeloid
      leukemia (AML) with special reference to the presence or absence of mixed-lineage
      leukemia gene (MLL) rearrangements. METHODS: Bone marrow samples from 313
      children with B-precursor ALL and 130 children with de novo AML were studied at
      diagnosis. Southern blot analysis was used to detect MLL rearrangements, and
      reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was used to
      detect common MLL fusion transcripts. Complementary DNA panhandle PCR was used to
      identify the infrequent or unknown MLL partner genes. DNA PCR or RT-PCR followed
      by direct sequencing was performed to detect mutations at codons 12, 13, and 61
      of the N-Ras and K-Ras genes. RESULTS: Twenty of 313 patients with B-precursor
      ALL and 17 of 130 patients with de novo AML had MLL rearrangements. N-Ras
      mutations were detected in 2 of 20 patients with MLL-positive ALL and in 27 of
      293 patients with MLL-negative ALL (P = 1.000). N-Ras mutations were detected in
      2 of 17 patients with MLL-positive AML and in 14 of 113 patients with MLL
      negative AML (P = 1.000). K-Ras mutations were present in 8 of 20 patients with
      MLL-positive ALL compared with 32 of 293 patients with MLL-negative ALL (P =
      0.001). K-Ras mutations were detected in 3 of 17 patients with MLL-positive AML
      compared with 5 of 113 patients with MLL-negative AML (P = 0.069). CONCLUSIONS:
      Ras mutations were detected in 20.8% of patients with childhood B-precursor ALL
      and in 17.7% of patients with childhood AML. MLL-positive B-precursor ALL was
      associated closely with Ras mutations (50%), especially with K-Ras mutations
      (40%), whereas MLL-positive AML was not associated with Ras mutations.

PMID- 16404745
TI  - A novel hereditary small vessel disease of the brain.
AB  - OBJECTIVE: Only few hereditary ischemic small vessel diseases of the brain (SVDB)
      have been reported so far. Cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent of
      them. Herein, we report a family affected by a SVDB distinct from CADASIL.
      METHODS: After the occurrence of a small deep infarct associated with white
      matter lesions both in a 46-year-old man and in his 52-year-old sister, clinical
      and neuroimaging investigations were conducted in 13 of their relatives
      originating from Portugal. Other investigations included (1) skin biopsy
      immunostaining with a Notch3 monoclonal antibody, (2) sequencing of the 23 exons
      encoding the epidermal growth factor-like domains of the NOTCH3 gene, and (3) a
      NOTCH3 locus haplotype analysis. RESULTS: Diffuse white matter hyperintensities
      were observed on T2-weighted magnetic resonance imaging (MRI) in six individuals.
      In contrast with MRI results in the father and paternal uncle of the proband who
      were hypertensive, white matter lesions were extensive in the mother who had no
      vascular risk factor. MRI data in four asymptomatic family members together with
      the results in the two initial cases were suggestive of an underlying hereditary
      small vessel disease of the brain. Skin biopsy and NOTCH3 gene mutation screening
      were negative. Haplotype analysis excluded the NOTCH3 locus. INTERPRETATION:
      These data strongly suggest that this family is affected by a novel hereditary
      small vessel disease of the brain and that the mutated gene is distinct from
      NOTCH3.

PMID- 16404746
TI  - Peptidomics: identification and quantification of endogenous peptides in
      neuroendocrine tissues.
AB  - Neuropeptides perform a large variety of functions as intercellular signaling
      molecules. While most proteomic studies involve digestion of the proteins with
      trypsin or other proteases, peptidomics studies usually analyze the native
      peptide forms. Neuropeptides can be studied by using mass spectrometry for
      identification and quantitation. In many cases, mass spectrometry provides an
      understanding of the precise molecular form of the native peptide, including post
      translational cleavages and other modifications. Quantitative peptidomics studies
      generally use differential isotopic tags to label two sets of extracted peptides,
      as done with proteomic studies, except that the Cys-based reagents typically used
      for quantitation of proteins are not suitable because most peptides lack Cys
      residues. Instead, a number of amine-specific labels have been created and some
      of these are useful for peptide quantitation by mass spectrometry. In this
      review, peptidomics techniques are discussed along with the major findings of
      many recent studies and future directions for the field.

PMID- 16404747
TI  - Immunoreactivity of p16 in anal cytology specimens: histologic correlation.
AB  - BACKGROUND: Cytology has been proposed as a potential screening tool in the
      evaluation of squamous anorectal disease in view of the morphologic similarities
      between anal and cervical squamous lesions. Previous studies have demonstrated
      that p16 overexpression correlates with the degree of dysplasia in the uterine
      cervix with promising results. Due to potential diagnostic pitfalls in anal
      cytology, p16 overexpression in these specimens was studied. METHODS: Patients
      with anorectal cytology who underwent follow-up biopsy within 1 year were
      selected. Forty-three anorectal cytologic specimens from 29 patients were
      selected. One slide of each case was destained. Avidin-biotin immunocytochemical
      studies with the monoclonal antibody CINtec p16(INK4a) were performed. The
      results of the p16 immunostaining were correlated with the histologic findings.
      RESULTS: Twenty-eight of the 43 cases demonstrated the presence of squamous cells
      immunoreactive for p16 in cytology specimens. The p16-positive cells were
      identified in cases of low-grade squamous intraepithelial lesion (LSIL) (n = 3
      cases), high-grade squamous intraepithelial lesion (HSIL) (n = 22 cases), and
      invasive squamous carcinoma (n = 1 case), and in 2 cases with negative follow-up
      biopsies. No cell immunoreactive for p16 was found in 15 cases (5 benign cases
      and 10 cases with either LSIL or HSIL). The sensitivity and specificity of p16
      immunoreactivity in the detection of anal intraepithelial neoplasia or carcinoma
      were 72% and 71%, respectively. The positive and negative predictive values were
      93% and 33%, respectively. CONCLUSIONS: The presence of p16 immunoreactivity is a
      good predictor of dysplasia in anal specimens. However, the sensitivity and
      specificity of this marker are not high.

PMID- 16404748
TI  - Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation.
AB  - OBJECTIVE: To determine whether the devastating outcome of neonatal-onset glycine
      encephalopathy (NKH) could be improved by instituting treatment immediately at
      birth rather than after symptoms are already well established. METHODS: A newborn
      with NKH diagnosed prenatally following the neonatal death of a previous affected
      sibling was treated from birth with oral sodium benzoate (250 mg/kg/day) and the
      NMDA receptor antagonist ketamine (15 mg/kg/day) immediately after sampling cord
      blood and cerebrospinal fluid (CSF) for glycine determination. Glycine cleavage
      system (CGS) activity was determined in placental tissue. Mutation analysis was
      performed by sequencing all GLDC, GCSH and AMT exons. RESULTS: CSF glycine (99
      micromol/L, reference 3.8-8.0) was already markedly elevated at birth. GCS
      activity in placental tissue was severely reduced (2.6% of controls). A novel
      homozygous GLDC c.482A-->G(Y161C) missense mutation was identified. Neonatal
      hypotonia and apnea did not occur but the long-term outcome was poor, with
      intractable seizures and severe psychomotor retardation. This contrasts with the
      favorable outcome with early treatment in variant NKH with mild GCS deficiency
      (Ann Neuol 2004;56:139-143). INTERPRETATION: Prospective treatment with this
      regimen can favorably modify the early neonatal course of severe NKH but does not
      prevent the poor long-term outcome, suggesting glycine-induced prenatal injury
      and/or ongoing postnatal damage.

PMID- 16404749
TI  - Acute and long-term outcomes of the novel side access (SLK-View) stent for
      bifurcation coronary lesions: a multicenter nonrandomized feasibility study.
AB  - OBJECTIVE: To evaluate technical feasibility and procedural safety of SLK-View
      stent for treating bifurcation lesions. BACKGROUND: Percutaneous treatment of
      coronary bifurcation lesions represents a technical challenge. Several stenting
      techniques and dedicated devices have proven unsuccessful, with high rates of
      side branch occlusion at index procedure and follow-up. METHODS: Eighty one
      patients with 84 de novo coronary artery lesions involving a major side branch
      underwent SLK-View (Advanced Stent Technologies, Inc., Pleasanton, CA) stent
      implantation with subsequent kissing balloon post dilatation. SLK-View stent is a
      new scaffolding device incorporating a side aperture that allows access to the
      side-branch of a bifurcation after deployment of the stent in main vessel. All
      patients underwent angiographic follow-up at 6 months. Procedural, in-hospital,
      and 6-month follow-up outcomes were examined. RESULTS: The lesions were located
      in left main (n = 11), left anterior descending (n = 50), left circumflex (n =
      8), right coronary artery (n = 7), and 1 ramus intermedius. The most frequent
      lesions (44.1%) were true bifurcations. Successful stent delivery to bifurcation
      was accomplished in 82/84 of the cases (97.6%). Technical success was obtained in
      99 and 94% of main vessel and side branches, respectively. Stenting in side
      branch was performed in 21 lesions (25%). Side-branches were accessed effectively
      in 100% of bifurcations postprocedurally. Binary restenosis rate at 6-month
      follow-up was 28.3% and 37.7% for main vessel and side-branch, respectively. TLR
      rate at 6-month follow-up was 21% and CABG rate of 6%. CONCLUSION: In this
      consecutive multicenter series of patients with coronary bifurcation lesions,
      this novel side-branch access stent proved feasible, with a high procedural
      success rate, while maintaining side-branch access.

PMID- 16404750
TI  - The impact of circadian variation on outcomes in emergency acute anterior
      myocardial infarction percutaneous coronary intervention.
AB  - OBJECTIVES: We investigated the impact of primary coronary angioplasty performed
      during night and compared to the impact of that performed during day-time on
      outcomes of patients with acute ST elevation anterior wall myocardial infarction
      (AMI). METHODS: We prospectively followed 273 consecutive patients of whom 160
      (58.6%) were treated during day time (8:00 a.m. to 6 p.m.) and 113 (41.4%) were
      treated "off hours"/at night (6 p.m. to 8 a.m.). Baseline demographics,
      angiographic factors, and clinical outcomes (death, recurrent AMI, and need for
      repeat revascularization) were compared between the groups. RESULTS: Baseline
      clinical characteristics were similar between the two groups. Unadjusted
      mortality at one-month was significantly higher among patients who were treated
      during night compared with those treated at day-time (9.7% vs. 3.1% P = 0.03), as
      was adverse cardiac event rate (15.9% vs. 6.9%; P = 0.02). Multiple logistic
      regression analysis adjusted for the CADILLAC risk score demonstrated that this
      score, which includes baseline LVEF, renal failure, Killip class, final TIMI
      flow, age>65 years, anemia, and the number of coronary vessel diseases, is a
      significant predictor of one-month mortality, while the effect of time of
      treatment was borderline (night vs. day; odds ratio 2.7; 95% confidence interval,
      0.8-9.4; P = 0.095). CONCLUSIONS: The results of this study indicate that
      patients with anterior myocardial infarction treated during night time have worse
      unadjusted short-term clinical outcomes despite no delay from onset of symptoms
      to actual treatment. Larger studies are needed in order to identify potential
      contributors to this phenomenon.

PMID- 16404753
TI  - Antibiotics and much more.

PMID- 16404754
TI  - Serine octamers: cluster formation, reactions, and implications for biomolecule
      homochirality.
AB  - The emergence of homochirality continues to be one of the most challenging topics
      associated with the origin of life. One possible scenario is that aggregates of
      amino acids might have been involved in a sequence of chemical events that led to
      chiral biomolecules in self-replicating systems, that is, to homochirogenesis.
      Serine is the amino acid of principal interest, since it forms "magic-number"
      ionic clusters composed of eight amino acid units, and the clusters have a
      remarkable preference for homochirality. These serine octamer clusters (Ser8) can
      be generated under simulated prebiotic conditions and react selectively with
      other biomolecules. These observations led to the hypothesis that serine
      reactions were responsible for the first chiral selection in nature which was
      then passed through chemical reactions to other amino acids, saccharides, and
      peptides. This Review evaluates the chemistry of Ser8 clusters and the
      experimental evidence that supports their possible role in homochirogenesis.

PMID- 16404755
TI  - Berry pseudorotation mechanism for the interpretation of the 19F NMR spectrum in
      PF5 by ab initio molecular dynamics simulations.
AB  - For the first time, theoretical evidence that confirms the importance of the
      Berry pseudorotation process in the interpretation of the 19F NMR spectrum of
      phosphorus pentafluoride (PF5) is presented. Ab initio molecular dynamics
      simulations have been performed to generate a large number of configurations used
      for NMR parameter computations at the density functional theory level. Two
      different temperatures were set to highlight the effect of pseudorotation process
      on the NMR spectrum. Average 19F chemical shifts and spin-spin coupling constants
      calculated for the five fluorine atoms converge towards the NMR equivalence of
      the five atoms when the Berry pseudorotation mechanism is accounted for.

PMID- 16404757
TI  - Conductivity of oriented bis-azo polymer films.
AB  - The conductivity properties of electro-optic, photoaddressable, dense bis-azo
      chromophore polymer films are investigated by using samples corona poled at
      various temperatures. A dielectric spectrometer is applied to measure the
      frequency dependence of the conductivity at different temperatures before and
      after heating the material to above the glass transition temperature. The results
      show that the orientation of the chromophores changes the charge-carrier
      mobility. Ionic conductivity dominates in a more disordered configuration of the
      material, while the competing process of hole hopping takes over as a transition
      to a liquid-crystalline phase occurs when the material is heated to much higher
      than the glass transition temperature. Such microcrystallization strongly
      enhances the conductivity.

PMID- 16404756
TI  - Structure of the HOOO radical in liquid water: a theoretical study.
AB  - The HOOO radical is supposed to play a role in ozone chemistry, both in the gas
      phase and aqueous media. We discuss the influence of the solvent on the
      electronic and geometrical structure of this radical using density functional and
      high-level ab initio calculations together with continuum, discrete, and discrete
      continuum solvent models. Solute-solvent electrostatic interactions are shown to
      be fundamental, and lead to a noticeable stabilization of the radical, which
      should adopt a trans conformation in aqueous media. In fact, no energy minimum
      for the cis conformation is predicted in these conditions.

PMID- 16404758
TI  - Field effect of screened charges: electrical detection of peptides and proteins
      by a thin-film resistor.
AB  - For many biotechnological applications the label-free detection of biomolecular
      interactions is becoming of outstanding importance. In this Article we report the
      direct electrical detection of small peptides and proteins by their intrinsic
      charges using a biofunctionalized thin-film resistor. The label-free selective
      and quantitative detection of small peptides and proteins is achieved using
      hydrophobized silicon-on-insulator (SOI) substrates functionalized with lipid
      membranes that incorporate metal-chelating lipids. The response of the nanometer
      thin conducting silicon film to electrolyte screening effects is taken into
      account to determine quantitatively the charges of peptides. It is even possible
      to detect peptides with a single charge and to distinguish single charge
      variations of the analytes even in physiological electrolyte solutions. As the
      device is based on standard semiconductor technologies, parallelization and
      miniaturization of the SOI-based biosensor is achievable by standard CMOS
      technologies and thus a promising basis for high-throughput screening or
      biotechnological applications.

PMID- 16404759
TI  - Catalytic enantioselective hydrogenolysis of [Cr(CO)3(5,8-dibromonaphthalene)].

PMID- 16404760
TI  - Apoptolidin: induction of apoptosis by a natural product.
AB  - Apoptolidin is a natural product that selectively induces apoptosis in several
      cancer cell lines. Apoptosis, programmed cell death, is a biological key pathway
      for regulating homeostasis and morphogenesis. Apoptotic misregulations are
      connected with several diseases, in particular cancer. The extrinsic way to
      apoptosis leads through death ligands and death receptors to the activiation of
      the caspase cascade, which results in proteolytic degradation of the cell
      architecture. The intrinsic pathway transmits signals of internal cellular damage
      to the mitochondrion, which loses its structural integrity, and forms an
      apoptosome that initiates the caspase cascade. Compounds which regulate apoptosis
      are of high medical significance. Many natural products regulate apoptotic
      pathways, and apoptolidin is one of them. The known synthetic routes to
      apoptolidin are described and compared in this Review. Selected further natural
      products which regulate apoptosis are introduced briefly.

PMID- 16404761
TI  - A new approach to the inhibition of metallo-beta-lactamases.

PMID- 16404762
TI  - Diagnostics of single base-mismatch DNA hybridization on gold nanoparticles by
      using the hyper-Rayleigh scattering technique.

PMID- 16404763
TI  - Ultra-wideline 27Al NMR investigation of three- and five-coordinate aluminum
      environments.
AB  - Ultra-wideline 27Al NMR experiments are conducted on coordination compounds with
      27Al nuclei possessing immense quadrupolar interactions that result from
      exceptionally nonspherical coordination environments. NMR spectra are acquired
      using a methodology involving frequency-stepped, piecewise acquisition of NMR
      spectra with Hahn-echo or quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) pulse
      sequences, which is applicable to any half-integer quadrupolar nucleus with
      extremely broad NMR powder patterns. Despite the large breadth of these central
      transition powder patterns, ranging from 250 to 700 kHz, the total experimental
      times are an order of magnitude less than previously reported experiments on
      analogous complexes with smaller quadrupolar interactions. The complexes examined
      feature three- or five-coordinate aluminum sites: trismesitylaluminum (AlMes3),
      tris(bis(trimethylsilyl)amino)aluminum (Al(NTMS2)3), bis[dimethyl
      tetrahydrofurfuryloxide aluminum] ([Me2-Al(mu-OTHF)]2), and bis[diethyl
      tetrahydrofurfuryloxide aluminum] ([Et2-Al(mu-OTHF)]2). We report some of the
      largest 27Al quadrupolar coupling constants measured to date, with values of
      C(Q)(27Al) of 48.2(1), 36.3(1), 19.9(1), and 19.6(2) MHz for AlMes3, Al(NTMS2)3,
      [Me2-Al(mu-OTHF)]2, and [Et2-Al(mu-OTHF)]2, respectively. X-ray crystallographic
      data and theoretical (Hartree-Fock and DFT) calculations of 27Al electric field
      gradient (EFG) tensors are utilized to examine the relationships between the
      quadrupolar interactions and molecular structure; in particular, the origin of
      the immense quadrupolar interaction in the three-coordinate species is studied
      via analyses of molecular orbitals.

PMID- 16404764
TI  - Ab initio study of free-radical polymerization: polyethylene propagation
      kinetics.
AB  - The chain-length dependence of the propagation rate coefficient for the free
      radical polymerization of ethylene was investigated on an ab initio basis.
      Polyethylene was chosen as a test system because of its structural simplicity. Ab
      initio density functional theory at the B3LYP/6-31g(d) level was applied to study
      the kinetics of a set of addition reactions of a systematically growing radical
      alkyl chain to ethylene. These reactions are propagation steps in the free
      radical polymerization of ethylene. Special attention was paid to low normal
      modes corresponding to internal rotations (IR), since the latter are important
      for an accurate description of the partition functions. The effect of coupling of
      the IR modes is also discussed. A comparison is made with the propagation rate
      constant derived from experiment. The results indicate that the propagation rate
      coefficient has largely converged by the hexyl radical stage, though a weaker
      chain-length dependence of k(p) for longer chains was detected.

PMID- 16404766
TI  - The equilibrium structure of ferrocene.
AB  - The molecular structures of ferrocene in the eclipsed (equilibrium) and staggered
      (saddle-point) conformations have been determined by full geometry optimizations
      at the levels of second-order Moller-Plesset (MP2) theory, coupled-cluster
      singles-and-doubles (CCSD) theory, and CCSD theory with a perturbative triples
      correction [CCSD(T)] in a TZV2P+f basis set. Existing experimental results are
      reviewed. The agreement between the CCSD(T) results and experiment is in all
      cases excellent; the calculated structure parameters and the barrier to internal
      rotation of the ligand rings differ from the most accurate experimental values by
      less than two estimated standard deviations. The CCSD(T) calculations for single
      configuration-dominated transition metal complexes such as ferrocene thus appear
      to have an accuracy comparable to that observed for molecules containing only
      first- and second-row atoms, and to be of a quality similar to that obtained
      experimentally. A comparison with previous DFT results indicates that the B3LYP
      model gives overall the best DFT results, with a deviation of around 2 pm for the
      metal-carbon distance and smaller errors for the cyclopentadienyl rings.

PMID- 16404767
TI  - Current topics in smectic liquid crystal research.
AB  - Interest in the smectic liquid-crystalline state of matter received a substantial
      boost with the discovery by Meyer in the mid-1970s that a chiral smectic C (SmC*)
      phase exhibits a spontaneous electric polarization, and with the subsequent
      demonstration by Clark and Lagerwall of the surface-stabilized SmC* ferroelectric
      liquid crystal at the beginning of the 1980s. Since then, chiral smectic phases
      and their plethora of polar effects have dominated the research in this field,
      which today has reached a mature state where the first commercial microdisplay
      applications are now shipping in millions-per-year quantities. In this Review we
      discuss some of the topics of highest interest in current smectic liquid crystal
      research, and address application-relevant research (de Vries-type tilting
      transitions without defect generation and high-tilt antiferroelectric liquid
      crystals with perfect dark state) as well as more curiosity-driven research (the
      nature and origin of the chiral smectic C subphases and their intermediate
      frustrated states between ferro- and antiferroelectricity).

PMID- 16404768
TI  - Spectroscopy and femtosecond dynamics of type-II CdTe/CdSe core-shell quantum
      dots.
AB  - Syntheses of CdTe/CdSe type-II quantum dots (QDs) using CdO and CdCl2 as
      precursors for core and shell, respectively, are reported. Characterization was
      made via near-IR interband emission, transmission electron microscopy (TEM),
      energy dispersive spectroscopy (EDX), and X-ray diffraction (XRD). Femtosecond
      fluorescence upconversion measurements on the relaxation dynamics of the CdTe
      core (in CdTe/CdSe) emission and CdTe/CdSe interband emission reveal that as the
      size of the core increases from 5.3, 6.1 to 6.9 nm, the rate of photoinduced
      electron separation decreases from 1.96, 1.44 to 1.07 x10(12) s(-1). The finite
      rates of the initial charge separation are tentatively rationalized by the small
      electron-phonon coupling, causing weak coupling between the initial and charge
      separated states.

PMID- 16404769
TI  - Photoinduced energy- and electron-transfer processes in dinuclear Ru(II)-Os(II),
      Ru(II)-Os(III), and Ru(III)-Os(II) trisbipyridine complexes containing a shape
      persistent macrocyclic spacer.
AB  - The PF6- salt of the dinuclear [(bpy)2Ru(1)Os(bpy)2]4+ complex, where 1 is a
      phenylacetylene macrocycle which incorporates two 2,2'-bipyridine (bpy) chelating
      units in opposite sites of its shape-persistent structure, was prepared. In
      acetonitrile solution, the Ru- and Os-based units display their characteristic
      absorption spectra and electrochemical properties as in the parent homodinuclear
      compounds. The luminescence spectrum, however, shows that the emission band of
      the Ru(II) unit is almost completely quenched with concomitant sensitization of
      the emission of the Os(II) unit. Electronic energy transfer from the Ru(II) to
      the Os(II) unit takes place by two distinct processes (k(en) = 2.0x10(8) and
      2.2x10(7) s(-1) at 298 K). Oxidation of the Os(II) unit of
      [(bpy)2Ru(1)Os(bpy)2]4+ by Ce(IV) or nitric acid leads quantitatively to the
      [(bpy)2Ru(II)(1)Os(III)(bpy)2]5+ complex which exhibits a bpy-to-Os(III) charge
      transfer band at 720 nm (epsilon(max) = 250 M(-1) cm(-1)). Light excitation of
      the Ru(II) unit of [(bpy)2Ru(II)(1)Os(III)(bpy)2]5+ is followed by electron
      transfer from the Ru(II) to the Os(III) unit (k(el,f) = 1.6x10(8) and 2.7x10(7)
      s(-1)), resulting in the transient formation of the
      [(bpy)2Ru(III)(1)Os(II)(bpy)2]5+ complex. The latter species relaxes to the
      [(bpy)2Ru(II)(1)Os(III)(bpy)2]5+ one by back electron transfer (k(el,b) =
      9.1x10(7) and 1.2x10(7) s(-1)). The biexponential decays of the
      [(bpy)2*Ru(II)(1)Os(II)(bpy)2]4+, [(bpy)2*Ru(II)(1)Os(III)(bpy)2]5+, and
      [(bpy)2Ru(III)(1)Os(II)(bpy)2]5+ species are related to the presence of two
      conformers, as expected because of the steric hindrance between hydrogen atoms of
      the pyridine and phenyl rings. Comparison of the results obtained with those
      previously reported for other Ru-Os polypyridine complexes shows that the
      macrocyclic ligand 1 is a relatively poor conducting bridge.

PMID- 16404770
TI  - Designing a new two-dimensional molecular layout by hydrogen bonding.

PMID- 16404771
TI  - Blue phases at work!

PMID- 16404774
TI  - Axillary surgery for breast cancer.

PMID- 16404775
TI  - Senior original author's response to: High risk of lower limb neuropraxia and
      litigations for a better view of the perineum.

PMID- 16404776
TI  - Attenuation of negative pain affect produced by unilateral spinal nerve injury in
      the rat following anterior cingulate cortex activation.
AB  - The affective and the sensory dimensions of pain processing can be differentiated
      in humans through the use of questionnaires and verbal communication. It is
      difficult to dissociate these two components of pain processing in rodents, and
      an understanding of the underlying mechanisms for each component is unclear. The
      quantification of a novel behavioral response to a repeated noxious cutaneous
      stimulus together with a measurement of tactile allodynia in nerve-injured rats
      might be used to differentially explore the sensory and affective components of
      pain processing in the rat. The present study utilized electrical stimulation of
      the anterior cingulate cortex, a structure implicated in affective pain
      processing but not sensory processing, in nerve-injured rats (L5 spinal nerve
      ligation) and found that the aversive quality of noxious cutaneous hindpaw
      stimulation was attenuated. There were no effects on sensory processing, because
      anterior cingulate cortex stimulation did not produce an anti-allodynic effect in
      L5 spinal nerve ligation animals. Furthermore, anterior cingulate cortex
      stimulation in animals with bilateral ventrolateral periaqueductal gray area
      lesions did not affect tactile sensitivity in L5 spinal nerve ligation rats,
      indicating that an endogenous pain suppression system was not likely activated by
      anterior cingulate cortex stimulation. However, bilateral ventrolateral
      periaqueductal gray area lesions in L5 spinal nerve ligation rats blocked the
      effect produced by anterior cingulate cortex stimulation in the place
      escape/avoidance paradigm. Specifically, these animals avoided noxious
      stimulation of the allodynic paw significantly more than anterior cingulate
      cortex-stimulated, sham or incomplete ventrolateral periaqueductal gray area
      lesioned, L5 spinal nerve ligation animals. These findings provide the first
      quantified report that the activation of the anterior cingulate cortex reduced
      the aversive quality of repeated noxious tactile stimulation in nerve-injured
      animals without interfering with normal sensory processing. This effect might
      require the presence of an intact ventrolateral periaqueductal gray area. It is
      concluded that the selective manipulation of the anterior cingulate cortex has
      different effects on pain affect and sensory processing in a rodent model of
      neuropathic pain.

PMID- 16404777
TI  - Method for management of an infected gastrostomy.

PMID- 16404778
TI  - The use of a cell saver during repair of ruptured  abdominal aortic aneurysms
      increases  early survival.

PMID- 16404779
TI  - Warm povidone-iodine for surgical skin  preparation.

PMID- 16404780
TI  - The two-artery clip manoeuvre to remove a  needle from a foot.

PMID- 16404781
TI  - Mesh positioning in laparoscopic TEP hernia  repair: the easy way.

PMID- 16404782
TI  - The TRPV1 receptor: target of toxicants and therapeutics.
AB  - Understanding the structural and functional complexities of the transient
      receptor potential vanilloid receptor (TRPV1) is essential to the therapeutic
      modulation of inflammation and pain. Because of its central role in initiating
      inflammatory processes and integrating painful stimuli, there is an
      understandable interest in its pharmacological manipulation
      (sensitization/desensitization). The present Highlight entitled "TRPV1
      antagonists elevate cell surface populations of receptor protein and exacerbate
      TRPV1 mediated toxicities in human lung epithelial cells" describes how exposure
      to various antagonists produces TRPV1 sensitization and proposes a possible
      mechanistic explanation to that sensitization.

PMID- 16404783
TI  - [Child vaccination protects grandparents].

PMID- 16404784
TI  - [High dosage induction brings new hope].

PMID- 16404785
TI  - Early-stage breast cancer rates rise sharply as invasive breast cancer levels
      off.

PMID- 16404786
TI  - Possible antipsychotic effect of fluvoxamine.

PMID- 16404787
TI  - Right ventricular outflow tract stenting in tetrology of fallot with restrictive
      ventricular septal defect.
AB  - A 6-month-old child with worsening cyanosis from birth, hypercyanotic spells and
      failure to thrive, was admitted with severe desaturation. Systemic saturation was
      < 56%, and echocardiography revealed severe infundibular pulmonary stenosis with
      normal pulmonary valve and a restrictive ventricular septal defect. The child
      underwent percutaneous stenting of the right ventricular outflow tract (RVOT),
      with good reduction in gradient and clinical stabilization. The child is being
      followed up for elective intracardiac repair.

PMID- 16404788
TI  - Unrecognized stent embolization causing recurrent chest pain.
AB  - Numerous methods have been described for retrieving or addressing stents that
      have embolized in the coronary arteries. Almost all of these prior reports
      address the "freshly" embolized stent with retrieval or deployment occurring
      during the same index procedure during which the embolization occurred. We
      describe a case of a thrombosed, chronically embolized coronary stent.

PMID- 16404789
TI  - One year follow-up of sirolimus-eluting stent in a cardiac post-transplant
      patient.

PMID- 16404790
TI  - Double-catheter technique for catheterization of the left coronary artery in a
      patient with an ascending aorta aneurysm.
AB  - We describe our experience performing cardiac catheterization of the left
      coronary artery in a patient with an aneurysm of the ascending aorta using a
      double-catheter technique. A 7 Fr guiding catheter was advanced into the aortic
      root and a longer multipurpose diagnostic catheter was passed through the guiding
      catheter, which enabled the extension of the whole catheter system. In addition,
      this technique allowed us to reach the ostium of the left coronary artery and
      perform coronary angiography.

PMID- 16404791
TI  - Acute coronary occlusion and myocardial infarction secondary to blunt chest
      trauma from an automobile airbag deployment.
AB  - Automobile airbags have been universally installed to save lives in motor vehicle
      accidents, but have also been linked with facial and thoracic burns and chest
      trauma during rapid deployment. Blunt trauma to the chest may result in
      electrical and mechanical injuries to the heart and great vessels. We report a
      case of a 19-year-old man who presented with acute myocardial infarction
      following a blunt chest trauma from an automobile airbag deployment. Although
      mechanical complications resulting from airbag injury have been reported in the
      past, this is the first report of an acute thrombotic coronary occlusion
      triggered by the rapid airbag deployment. The case underscores the importance of
      systematic clinical evaluation to guide management in patients with confounding
      clinical presentation.

PMID- 16404792
TI  - Coronary artery aneurysm following drug-eluting stent implantation.

PMID- 16404793
TI  - Transcatheter closure of atypical right-to-left shunts after Fontan surgery.
AB  - Atypical right-to-left shunts following Fontan surgery were closed by
      transcatheter techniques using various devices in 4 patients. Three had variants
      of hypoplastic left heart syndrome, while the other had tricuspid atresia. Large
      Fontan baffle leaks were present in 2, a residual fistula from the inferior vena
      cava to the coronary sinus was present in 1, and another patient had surgical
      tube fenestration of an extracardiac conduit. When careful catheter and
      transesophageal echocardiographic exploration is performed, the selection of
      appropriate devices makes closure of these defects feasible.

PMID- 16404794
TI  - Toward high-throughput drug screening using mass spectrometry.
AB  - A critical overview on the potential of mass spectrometry-based methods regarding
      high-throughput screening analysis is presented. Within this scope, screening
      procedures will be discussed for simultaneous detection of several drug classes
      relevant to clinical and forensic toxicology or doping control in urine or blood
      using gas chromatography-mass spectrometry or liquid chromatography-mass
      spectrometry.

PMID- 16404795
TI  - High-performance liquid chromatography-mass spectrometry in the clinical
      laboratory.
AB  - The development of HPLC-atmospheric pressure ionization-mass spectrometry (HPLC
      MS) has presented clinical laboratories with a powerful analytic tool. The aim of
      this paper is to provide an overview of the current status of HPLC-MS in the
      clinical laboratory; to discuss the challenges to mass spectrometry in this
      setting; and to present some of the latest developments in instrumentation and
      illustrate their potential application. Currently, the major clinical
      applications for HPLC-MS are neonatal screening for metabolic disorders,
      therapeutic drug monitoring of immunosuppressant and HIV/AIDS drugs, and
      toxicological investigations. The major barrier to the uptake of this technology
      in the clinical laboratory is the initial capital outlay for instrumentation. A
      secondary reason is the lack of suitably trained scientists. The challenges that
      clinical HPLC-MS face are (I) ease of use and automation, (2) interpatient
      variability in relation to matrix effects, (3) availability of suitable internal
      standards, and (4) harmonization of methods to meet regulatory requirements. The
      development of the triple quadrupole linear ion trap mass analyzer allows the
      quantification power of a triple quadrupole mass analyzer to be combined with the
      scanning ability of an ion trap.This hybrid instrument allows different
      permutations of scan combinations. The combination of selected reactant
      monitoring and MS3 is an attractive combination for quantification. The ion
      source, atmospheric pressure photoionization, has recently been developed and is
      well suited to nonpolar analytes, although its role is yet to be established.
      This ion source complements other interfaces used in HPLC-MS. Both of these
      advances in instrumentation add to the potential applications of HPLC-MS. How
      HPLC-MS goes forward into the clinical laboratory is dependent on clinical
      scientists, instrument manufacturers, and regulatory authorities.

PMID- 16404796
TI  - Application of bioaffinity mass spectrometry for analysis of ligands.
AB  - Bioaffinity mass spectrometry is a novel technology for analysis of binding
      proteins and their ligands. In this review, we introduce the concepts and
      principles of bioaffinity surface-enhanced laser desorption/ionization-time of
      flight mass spectrometry (SELDI-TOF MS). Various preactivated chip types and
      several approaches for binding of ligands or their binders to the chips are
      discussed. We also provide specific examples for the use of this technology for
      screening antibodies, analyzing ligands, glycoconjugates, protein-protein inter
      actions, and DNA (RNA) binding proteins. In pursuit of developing new tests or
      studies of mechanism of drug action in therapeutic drug monitoring practice, this
      technology may provide a more rapid approach for ligand-binder studies.

PMID- 16404797
TI  - Genetic associations of alcohol and aldehyde dehydrogenase with alcohol
      dependence and their mechanisms of action.
AB  - Two alcohol dehydrogenase genes (ADHIB and ADH1C on chromosome 4) and one
      aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional
      polymorphisms that are associated with lower rates of alcohol dependence. The
      ALDH2*2 allele,found almost exclusively in Asian populations, has the strongest
      relationship. The ADH1B*2, ADH1B*3, and ADHlC*i alleles, found in varying
      prevalence in different ethnic groups, have also been associated with lower rates
      of alcohol dependence. Studies of the ADHIBand ADH1C haplotypes, however, have
      shown that ADH1C*I is in linkage disequilibrium with ADHiB*2, and the ADH1C*i
      allele does not appear to have significant unique associations with alcohol
      dependence. The hypothesized mechanism underlying the associations of the ADH1B
      and ALDH2 polymorphisms with alcohol dependence is that the isoenzymes encoded by
      these alleles lead to an accumulation of acetaldehyde during alcohol metabolism.
      Based on their kinetic properties, ALDH2 *2 theoretically should lead to a slower
      removal of acetaldehyde than ALDH2*1, whereas ADH1B*2 and ADH1B*3 should lead to
      a more rapid production of acetaldehyde than ADHIB*I. It is further hypothesized
      that elevations in acetaldehyde cause more intense reactions to alcohol and lead
      to lower levels of alcohol intake. Data are consistent with the hypothesis that
      elevations in acetaldehyde, increased sensitivity to alcohol, and lower levels of
      drinking reflect the mechanism by which the ALDH2*2 allele reduces risk for
      alcohol dependence. There is also some evidence supporting this mechanism for the
      ADH1B*2 and ADHIB*3 alleles, but the results are less consistent. These findings
      highlight the value of trying to elucidate the mechanism by which genes
      ultimately give rise to differences in alcohol dependence through the examination
      of mediating behaviors.

PMID- 16404799
TI  - Can pharmacokinetic variability be controlled for the patient's benefit? The
      place of TDM for new AEDs.
AB  - The aim of this brief communication is to update our recent review on therapeutic
      drug monitoring (TDM) of the newer antiepileptic drugs (AEDs). The potential
      value of TDM is discussed in relation to their mode of action and their
      pharmacokinetic proper-ties. Data on the relationships between serum
      concentrations and clinical efficacy are limited, and few studies have been
      designed primarily to study these relationships. As yet there are no generally
      accepted target ranges for any of the new AEDs. For most drugs a wide range in
      serum concentration is associated with clinical efficacy,and there is a
      considerable overlap in serum concentrations related to toxicity and lack of
      clinical efficacy. Although the available documentation is clearly insufficient,
      the pharmacological properties of some of the drugs suggest that they may be
      suitable candidates for TDM. The primary role of TDM for both the newer and
      established AEDs is to identify an individual's optimum concentration and thus
      establish a reference value in that patient.

PMID- 16404798
TI  - Genetic influences on smoking: a brief review.
AB  - Smoking is a complex behavior influenced by environ-mental and genetic factors. A
      number of twin studies demonstrate genetic influences on multiple aspects of
      smoking including initiation, dependence, continuation, amount consumed, and
      cessation. It is likely that this genetic risk involves a complex interaction
      between multiple genes in different biologic pathways. These may include genes
      involved in the general aspect of dependence (eg, genes within the dopaminergic
      system) and those more specific to nicotine dependence (eg, genes encoding
      nicotinic acetylcholine receptors and nicotine-metabolizing enzymes). Genome-wide
      linkage analyses and gene association studies provide approaches for identifying
      these genes. This review provides a brief highlight of data from some of the
      candidate gene association studies and discusses some of the discrepancies found
      in the literature. In addition, the authors have reviewed some recent studies
      examining how genetic variations in drug-metabolizing enzymes and drug targets
      can influence the response to treatment with drugs such as bupropion and
      nicotine.These latter studies provide the potential for maximizing treatment
      efficacy by individualizing the type, dosage, and duration of the treatment based
      on an individual's genotype/phenotype. Significant advances have been made in
      understanding the genetic contribution to smoking behaviors. These and future
      studies will provide potential directions for novel prevention and treatment
      strategies.

PMID- 16404800
TI  - Integrating neurobiology and psychopathology into evidence-based treatment of
      social anxiety disorder.
AB  - Social anxiety disorder (SAD) is a common, chronic psychiatric disorder
      characterized by a persistent fear of social or performance situations in which
      embarrassment can occur. This disorder typically appears during the mid
      adolescent years and is unremitting throughout life if not properly treated. SAD
      presents as two subtypes: the more common and debilitating generalized form, and
      the nongeneralized form, which consists predominantly of performance anxiety. The
      majority of patients with SAD have comorbid mental disorders, including mood,
      anxiety, and substance abuse. No single development theory has been proposed to
      account for the origins of SAD, although current understanding of the etiology of
      SAD posits an interaction between psychological and biological factors. Risk
      factors include environmental and parenting influences and dysfunctional
      cognitive and conditioning events in early childhood. The neurobiology of SAD
      appears to involve neurochemical dysfunction, as evidenced by studies of
      neuroreceptor imaging, neuroendocrine function, and profiles of response to
      specific medications. Clinical trials have demonstrated that benzodiazepines and
      antidepressants are effective in the treatment of SAD. The selective serotonin
      reuptake inhibitors are emerging as the first-line treatment for SAD, based on
      their proven safety, tolerability, and efficacy. Goals for ongoing future
      research include development of approaches to achieve remission, to convert
      nonresponders and partial responders to full responders, and to prevent relapse
      and maintain long-term efficacy. This monograph explores the epidemiology,
      clinical presentation, and differential diagnosis of SAD, with a focus on neural
      circuitry of social relationships and neurochemical dysfunction. The prevalence,
      rates of recognition and treatment, patterns of comorbidity, quality-of-life
      issues, and natural history of SAD are discussed as well as pharmacologic and
      psychosocial treatment strategies for SAD.

PMID- 16404801
TI  - Pharmacokinetic variability of new antiepileptic drugs at different ages.
AB  - Newer generation antiepileptic drugs (AEDs) are increasingly used to treat
      epilepsies in infants, children, and the elderly. For rational prescribing in
      these populations, it is essential to understand the pharmacokinetic changes that
      occur during development and aging. Data obtained in recent years indicate that
      the apparent oral clearance (CL/F) of lamotrigine, topiramate, levetiracetam,
      oxcarbazepine, gabapentin, tiagabine, zonisamide, vigabatrin, and felbamate is
      considerably higher in children than in adults,the magnitude of the difference
      being on average in the order of 20%to 120%, depending on the drug and the age
      distribution of the assessed population. Information on the pharmacokinetics of
      these drugs in newborns is completely lacking or very sparse. Studies in the
      elderly have demonstrated that significant pharmacokinetic changes also occur at
      the other extreme of age. On average, CL/F values of newer generation AEDs have
      been found to be reduced by 10% to 50% compared with those found in young or
      middle-aged adults. These pharmacokinetic changes are clinically important and
      con-tribute to age-related differences in dosage requirements.

PMID- 16404802
TI  - Metabolic and endocrine disturbances in psychiatric disorders: a
      multidisciplinary approach to appropriate atypical antipsychotic utilization.
AB  - Patients with psychiatric disorders have an increased rate of cardiovascular
      morbidity and mortality compared with the general population. Metabolic issues
      such as weight gain, dyslipidemia, diabetes mellitus, diabetic ketoacidosis,and
      pancreatitis have been reported with the use of antipsychotic agents. Although
      atypical antipsychotics have not been linked directly to the development of
      metabolic syndrome, these medications have been shown to increase risk factors
      that can lead to metabolic and endocrine disturbances. Therefore, clinicians
      should provide ongoing monitoring for patients who are being treated for
      psychiatric disorders with these agents. According to the 2004 Consensus Report
      on Antipsychotics, screening measures should include baseline and follow-up
      monitoring of personal/family histories, weight (body mass index), waist
      circumference, blood pressure, fasting plasma glucose, and fasting lipid profile.

PMID- 16404803
TI  - Gender aspects of pharmacokinetics of new and old AEDs: pregnancy and breast
      feeding.
AB  - Alterations in drug disposition in pregnancy and drug transfer into breast milk
      during lactation are the most important gender-related aspects of the
      pharmacokinetics of antiepileptic drugs(AEDs). The effect of pregnancy on drug
      disposition has been fairly well characterized for the old AEDs. Total and
      unbound plasma concentrations of phenobarbital decline up to 50%. Total phenytoin
      levels may drop to approximately 40% of prepregnancy concentrations,but unbound
      concentrations considerably less. Unbound valproate levels remain unchanged
      despite a fairly marked decrease in total concentrations, and changes in unbound
      and total plasma concentrations of carbamazepine are minor. In contrast,
      pregnancy has a pronounced effect on lamotrigine, with a 300% increase in
      apparent clearance in the third trimester. Much less is known about the kinetics
      of other new AEDs during pregnancy. Umbilical cord/maternal plasma concentration
      ratios close to unity suggest free transplacental passage of most AEDs,whereas
      higher ratios indicate fetal accumulation of valproate and gabapentin.
      Milk/maternal plasma concentration ratios close to 1 demonstrate extensive
      transfer to breast milk of many AEDs including ethosuximide, gabapentin,
      lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide. Plasma
      levels are, however, in general low in the nursed infant, although
      pharmacological concentrations have been reported occasionally for carbamazepine,
      ethosuximide, lamotrigine, and phenobarbital. For most of the new-generation
      AEDs, there is an urgent need for further kinetic data from pregnancy and breast
      feeding.

PMID- 16404804
TI  - The pharmacokinetics and interactions of new antiepileptic drugs: an overview.
AB  - In the past decade 10 new antiepileptic drugs (AEDs)have been introduced:
      felbamate, gabapentin, lamotrigine, levetiracetem, oxcarbazepine, pregabalin,
      tiagabine, topiramate, vigabatrin,and zonisamide. The pharmacokinetics (PK) of
      these new AEDs as well as their potential for drug interactions are reviewed in
      this article. In general, new AEDs have better PK profiles and are less involved
      in drug interactions than the 4 established AEDs: phenobarbital,phenytoin,
      carbamazepine, and valproic acid. However, in spite of the large therapeutic
      arsenal of old and new AEDs, about 30% of epileptic patients are still not
      seizure-free, and thus, there is a substantial need to develop new AEDs.

PMID- 16404805
TI  - Clinical application of population pharmacokinetic methods developed for
      immunosuppressive drugs.
AB  - After a brief overview of the relevant exposure indices for cyclosporine (CsA)
      and mycophenolate mofetil (MMF), as well as of the different steps necessary to
      develop maximum a posteriori Bayesian estimators (MAP-BE), this paper presents
      applications of MAP-BE for CsA or MMF to clinical cases and clinical trials. Ina
      renal transplant patient under CsA, grade I chronic allograft nephropathy was
      found at the sixth month posttransplantation, with CsA CO slightly above the
      target range and C2 markedly below; the AUCO0-12 h Bayesian estimate was quite
      high, at 5.6 mg h/L, as compared with a mean value of 4.3+0.9 mg.h/L in stable
      renal transplants at this period; the inconsistent C2 level found could be
      explained by delayed absorption of CsA in this patient, in which case C2 no
      longer represents the major part of the AUC. The patient was switched to
      sirolimus, which resulted in a slow and significant improvement of graft function
      with no acute rejection. In a 50-year-old female renal transplant recipient
      administered MMF and CsA and with a very favorable outcome otherwise, progressive
      anemia appeared 8 months posttransplantation. Clinical investigations were
      negative,but Bayesian estimation showed a rather high MPA AUCO0-12 h (69.8 mg
      h/L). After MMF dose reduction, hemoglobin level progressively returned to
      normal, without erythropoietin injection or blood transfusion. Finally, the
      feasibility of accurate dose adjustment using these MAP-BE is shown through
      preliminary results from 2 ongoing multicenter clinical trials, 1 evaluating an
      AUC-controlled cyclosporine-sparing strategy in stable renal transplants, the
      second evaluating the benefit of MMF therapeutic drug monitoring based on MPA
      AUCO0-12 h in de novo renal transplant recipients.

PMID- 16404807
TI  - Recent trends in narcotic deaths.
AB  - The prevalence of overdose deaths from opioids is still generally increasing
      throughout the world. Heroin is still the predominant illicit opioid of interest
      to toxicology laboratories because of its continuing widespread availability and
      its ability to elicit respiratory depression and coma. In many countries
      methadone continues to play a major role in cases of drug toxicity because of its
      large-scale use to treat opioid dependency and its high potency and long duration
      of action. Increasingly, buprenorphine is being used as an alternative
      pharmacotherapy, and although apparently safer than methadone, it still has an
      inherent risk of toxicity when used with CNS depressants such as benzodiazepines
      or when injected. Morphine continues to be the dominant analgesic; however,
      oxycodone, hydromorphone, hydrocodone, and fentanyl are increasingly being used
      and will require increasing efforts by toxicology laboratories to ensure that
      these substances are adequately covered by testing programs.

PMID- 16404806
TI  - Biomarkers for toxicodynamic monitoring of immunosuppressants: NMR-based
      quantitative metabonomics of the blood.
AB  - Metabonomics is the latest "omics" science and provides metabolic endpoints of
      drug toxicity, drug efficacy, and pathophysiology. With high-resolution 'H-NMR
      (nuclear magnetic resonance)spectroscopy on body fluids (eg, urine, blood
      samples) used in combination with statistical tools, metabolic biomarkers of drug
      toxicity can be distinguished and validated. For 2 decades, immuno-suppressant
      cyclosporine (CsA) has been used in transplantation medicine as a potent
      calcineurin inhibitor with well-known nephrotoxic side effects. The combination
      of CsA with novel macrolide immunosuppressants-sirolimus (SRL) or everolimus
      (RAD)-has proved to have a beneficial synergistic immunosuppressive effect but
      may also possess an increased nephrotoxic potential. 1H-NMR spectroscopy was
      performed on the blood from CsA-, SRL-, and RAD (alone and in combination)
      treated rats to predict metabolic toxicity and to identify and quantify specific
      metabolic biomarkers. After 6 days of treatment with 10 mg/kg CsA, a significant
      increase in blood glucose, hydroxybutyrate, creatine+creatinine, trimethylamine-N
      oxide (TMAO), and cholesterol as well as a decrease in total glutathione
      concentrations were observed. SRL (3 mg/kg) enhanced the magnitude of CsA
      metabolic changes (enhanced toxicity),whereas combination with RAD (3 mg/kg)
      partly curtailed them. Together with pharmacokinetic studies, quantitative NMR
      based metabonomics represents a powerful tool for pharmacokinetic-pharmacodynamic
      toxicodynamic evaluation in drug research.

PMID- 16404808
TI  - [Echinococcosis of the liver and left retroperitoneal space simulating aortic
      aneurysm].

PMID- 16404809
TI  - [Greater omentum torsion].

PMID- 16404810
TI  - [A right-sided complete torsion of the ovary pedicle and uterine tube in a 9-year
      old child].

PMID- 16404811
TI  - ["Major amputations" in patients with occlusive diseases of the lower limb
      arteries].

PMID- 16404812
TI  - Methadone as a chemical weapon: two fatal cases involving babies.
AB  - Methadone is largely used for the substitution management of opiate-dependent
      individuals but can also be easily found on the black market. The first cases
      involving repetitive sedation linked to the use of methadone and subsequent death
      of 2 babies are reported. At the autopsy, no particular morphologic changes were
      noted except for pulmonary and visceral congestion. There was no evidence of
      violence, and the pathologist in both cases found no needle marks. Toxicological
      analyses, as achieved by GC/MS, demonstrated both recent and repetitive methadone
      exposure. In case 1, a 14-month-old girl was found dead at home. Blood
      concentrations were 1071 and 148 ng/mL for methadone and EDDP, respectively. Hair
      (6 cm) tested positive at 1.91 and 0.82 ng/mg for methadone and EDDP,
      respectively. In case 2, a 5-month-old girl was taken to hospital in a pediatric
      unit for coma. Antemortem blood analysis demonstrated methadone exposure (142
      ng/mL), and the baby was declared dead 12 days after admission. Hair analysis (5
      cm) by segmentation was positive for methadone in the range 1.0 (root) to 21.3
      ng/mg (end). The death of the babies was attributed to accidental asphyxia ina
      situation where methadone was considered as a chemical weapon. The mothers, who
      were the perpetrators in both cases, did not deny the use of methadone as a
      sedative drug.

PMID- 16404813
TI  - [Comment to the article by A.V. Cherkasov et al.: Assessment of efficacy of
      external drainage of the common bile duct. (Khirurgiya 2004; 6: 12-16)]].

PMID- 16404814
TI  - The DDAH-ADMA-NOS pathway.
AB  - An increasing number of reports in the literature indicate that endogenously
      produced inhibitors of nitric oxide synthase (NOS),particularly asymmetric
      dimethylarginine (ADMA), regulate nitric oxide generation in disease states. This
      article describes the biology of ADMA and the implications for cardiovascular
      physiology and pathophysiology.

PMID- 16404815
TI  - METLIN: a metabolite mass spectral database.
AB  - Endogenous metabolites have gained increasing interest over the past 5 years
      largely for their implications in diagnostic and pharmaceutical biomarker
      discovery. METLIN (http://metlin.scripps.edu), a freely accessible web-based data
      repository, has been developed to assist in a broad array of metabolite research
      and to facilitate metabolite identification through mass analysis. METLINincludes
      an annotated list of known metabolite structural information that is easily cross
      correlated with its catalogue of high-resolution Fourier transform mass
      spectrometry (FTMS) spectra, tandem mass spectrometry (MS/MS) spectra, and LC/MS
      data.

PMID- 16404816
TI  - Recent trends in analytical procedures in forensic toxicology.
AB  - Forensic toxicology is a very demanding discipline,heavily dependent on good
      analytical techniques. That is why new trends appear continuously. In the past
      years. LC-MS has revolutionized target compound analysis and has become the
      trend, also in toxicology. In LC-MS screening analysis, things are less
      straightforward and several approaches exist. One promising approach based on
      accurate LC-MSTOF mass measurements and elemental formula based library searches
      is discussed. This way of screening has already proven its applicability but at
      the same time it became obvious that a single accurate mass measurement lacks
      some specificity when using large compound libraries. CE too is a reemerging
      approach. The increasingly polar and ionic molecules encountered make it a
      worthwhile addition to e.g. LC, as illustrated for the analysis of GHB. A third
      recent trend is the use of MALDI mass spectrometry for small molecules. It is
      promising for its ease-of-use and high throughput. Unfortunately, re-ports of
      disappointment but also accomplishment, e.g. the quantitative analysis of LSD as
      discussed here, alternate, and it remains to be seen whether MALDI really will
      establish itself. Indeed, not all new trends will prove themselves but the mere
      fact that many appear in the world of analytical toxicology nowadays is, in
      itself, encouraging for the future of (forensic) toxicology.

PMID- 16404817
TI  - A medical ethics assessment of the case of Terri Schiavo.
AB  - The social, legal, and political discussion about the decision to stop feeding
      and hydration for Terri Schiavo lacked a medical ethics assessment. The authors
      used the principles of medical indications, quality of life, patient preference,
      and contextual features as a guide to medical decision-making in this case. Their
      conclusions include the following: (a) the use of a feeding tube inserted
      directly in to the stomach constituted artificial treatment; (b) the treatment
      prolonged biological life but did not lead to a cure and did not restore health;
      (c) quality of life was absent for the patient, with no sensation and no motor or
      cognitive functioning; and (d) by preponderance of medical opinion, she would
      have chosen not to live in a persistent vegetative state. The authors find the
      withdrawal of treatment was permissible and correct. It was not a choice between
      living and dying, but a decision of when to allow dying consistent with the
      patient's choice.

PMID- 16404818
TI  - What would Terri want? On the psychological challenges of surrogate decision
      making.
AB  - The Terri Schiavo case was unique in the media attention it garnered, but the
      decision making challenges faced by Terri's family are common ones encountered by
      all families who must make choices about the use of life-sustaining medical
      treatment for an incapacitated loved one. This article highlights three key
      issues that were particularly problematic in the Schiavo case, but that represent
      general psychological challenges inherent to the task of surrogate decision
      making. The 3 central points of uncertainty, and therefore conflict, in the
      Schiavo case concerned: (a) the appropriate standard by which medical decisions
      for Terri should be made, (b) the specific nature of Terri's wishes about the use
      of life-sustaining medical technology, and (c) the true extent of disability and
      prognosis for recovery represented by Terri's medical condition. No simple remedy
      is possible that will resolve all of the uncertainties inherent to surrogate
      decision making, but some general strategies for improving the quality of end-of
      life medical decisions are discussed.

PMID- 16404819
TI  - With just a quiver.

PMID- 16404820
TI  - Implications of the Schiavo case for understanding family caregiving issues at
      the end of life.
AB  - The case of Mrs. Terri Schiavo illustrates common themes in family caregiving at
      the end of life but is distinctive from most family caregiving situations in
      other ways. As occurred in Mrs. Schiavo's case, family members do act as both
      caregivers and decisionmakers for their loved ones at the end of life, often
      without the benefit of written advance directives. Family stress and conflict may
      result, yet seldom lead to court proceedings, legislative intervention, and media
      coverage as occurred in the Schiavo case. The importance of informal conflict
      resolution and the limitations of adversarial legal approaches are discussed.

PMID- 16404821
TI  - Terri Schiavo: a disability rights case.
AB  - The author argues that Terri Schiavo was a "person with a disability" who faced
      disability discrimination, a view that is consistent with national disability
      rights groups. The author notes that Schiavo was not "terminally ill" and that
      feeding tubes should not be considered "medical equipment." The belief that
      people with severe disabilities want to die is questioned, since many people who
      acquire severe disabilities change their minds about suicide, and implications
      for advance directives are explored. Finally, the author notes that although
      Terri Schiavo was a disabled woman, women's groups did not take up her cause.

PMID- 16404822
TI  - Extreme measures: a personal story of letting go.
AB  - The decision to withdraw life support from a loved one, especially in the absence
      of an advance directive, can be complicated and painful. This article is the
      author's personal account of her brother's brain injury, his resulting condition,
      and the choice made to allow his death. In addition, the author discusses how
      this experience affected her perspective on Terri Schiavo's death.

PMID- 16404823
TI  - Research agenda: venous thromboembolism in medical-surgical critically ill
      patients.

PMID- 16404824
TI  - NPH on TV.

PMID- 16404825
TI  - Might death sometimes take a holiday?

PMID- 16404826
TI  - Brown Medical School: class of 2005.

PMID- 16404827
TI  - Quality of life assessment in Thai postmenopausal women with an overactive
      bladder.
AB  - OBJECTIVE: To compare the quality of life (QoL) among 3 groups of Thai
      postmenopausal women with an overactive bladder (OAB), diabetes, and without
      these conditions. MATERIAL AND METHOD: A total cross-sectional cohort of 180
      postmenopausal women aged 48-60 years (60 had OAB, 60 diabetes and 60 controls)
      were recruited from the menopause clinic and diabetes clinic of Hatyai regional
      hospital between June and December 2003. Information on QoL were collected by the
      SF-36 questionnaire, validated for Thai women. RESULTS: There was no significant
      difference in the patient's demographic characteristics. All dimensions of QoL
      score of women with OAB and diabetes were lower than the scores of the controls.
      When compared with diabetes, OAB had significantly lower scores in the general
      health, social function and role-function emotional dimensions. CONCLUSION: QoL
      was significantly impaired in Thai postmenopausal women with OAB and diabetes
      compared to those women without these conditions. General health, social function
      and role-function emotional dimensions were particularly affected.

PMID- 16404828
TI  - Evaluation of female sterilization at Srinagarind Hospital.
AB  - A retrospective study of female sterilization at Srinagarind Hospital since 1978
      until 2002 revealed 35,094 cases those were in the period of 25 years. These
      operations were performed by physicians, medical students and trained nurses in
      21,383; 8,465 and 5,246 cases respectively. The presented cases were post partum
      tubal resection, interval tubal resection and cesarean section with tabul
      resection in 25,706; 4,4244 and 4,964 cases respectively. There were 350 cases of
      complication. The most common complication was tubal complications. Pregnancy
      post tubal resection were 74 cases or 0.21 percent. Different operators had
      statistically significant complication rates with Pearson chi square and Fisher
      exact test. Wound complication and pelvic pathology or operative difficulties
      were 2 types of statistically significant complications. Different types of
      operations had statistically significant complication rates. Six types of
      complications were tubal complication, wound complication, pregnancy, pelvic
      pathology or operative difficulties, bowel injury, and bladder injury.

PMID- 16404830
TI  - High-dose-rate interstitial brachytherapy in the management of carcinoma of the
      uterine cervix and other gynecologic malignancies.
AB  - OBJECTIVE: To report technique and experience of high-dose-rate (HDR)
      interstitial brachytherapy in the treatment of cervical carcinoma and other
      gynecologic malignancies. MATERIAL AND METHOD: Between April 2003 and October
      2004, ten patients (7-cervical carcinoma, 3-vaginal stump carcinoma) were treated
      with interstitial implant. Indications for implant include previous hysterectomy
      and previous pelvic radiation. Patient characteristics, implant technique, and
      initial outcomes were reported. RESULTS: Transperineal interstitial implant was
      performed using fluoroscopy-guided technique. Brachytherapy dose/fraction ranged
      from 500-750 cGy for 1 to 6 fractions. Combined external beam radiation was given
      in 8 patients. After 5-21 months follow-up, all the patients were alive. Local
      control was achieved in 9 patients. One patient had persistent disease at the
      implant site. No acute complication from the procedure or serious late
      complication was observed. CONCLUSION: Interstitial implant can be a treatment
      option in patients with gynecologic malignancies who have limitations with
      standard intracavitary insertion. This technique is feasible, providing good
      local control without serious complications. However, long-term follow-up is
      needed.

PMID- 16404829
TI  - Cost effectiveness of concurrent chemoradiation in comparison with radiation
      alone in locally advanced cervical cancer.
AB  - INTRODUCTION: Concurrent chemoradiation has been advocated to be more effective
      than radiation alone in the treatment of cervical cancer. However, it certainly
      has more side effects. Hence, it is worthwhile to investigate the cost
      effectiveness (CE) of concurrent chemoradiation in comparison with radiation
      alone in locally advanced cervical cancer. MATERIAL AND METHOD: The treatment of
      cervical cancer was modeled using the decision tree where the treatment option
      would be either concurrent chemoradiation or radiation alone. Patients receiving
      each treatment had different risks of tumor recurrence. Costs in this analysis
      were separated into four major categories: costs for treatment of cervical
      cancer, costs for treatment of major side effects, costs for follow up cancer
      patients, and costs for diagnosis including supportive care of recurrent cervical
      cancer Charges were used for the costs of chemotherapy, radiotherapy, drugs, and
      accessories. Unit cost was used for the costs of laboratory investigations, in
      patient and out-patient services. Costs incurred after the first year were
      discounted at an annual rate of 5%. The benefit was measured as months of life
      survived. The present study evaluated the patients to 5 years after complete
      treatment. RESULTS: The CE ratio in the concurrent chemoradiation group was 2,855
      and 1,835 Baht/month survived if the chemotherapy was given as in-patient and out
      patient respectively. The CE ratio in the radiation group equaled 2,366
      Baht/month survived. For the sensitivity analysis, in the situation that
      chemoradiation was not much better than radiation alone in terms that the
      recurrent rate from chemoradiation group was not more than 20% lower than the
      radiation group, radiation therapy alone would be more cost effective even if
      chemotherapy was given as an out-patient basis. CONCLUSION: Radiation alone was
      more cost effective than chemoradiation in the treatment of cervical cancer.
      Nevertheless, if chemotherapy was administered on an out-patient basis,
      chemoradiation will be more cost effective only if the recurrent rate from the
      chemoradiation group was more than 20% lower than the radiation group.

PMID- 16404831
TI  - Factors determining hospital admission of Thai elderly by a mailed survey.
AB  - OBJECTIVE: To study risk factors of hospital admission among older Thai adults.
      MATERIAL AND METHOD: Nationwide observational cross-sectional survey by mailed
      questionnaires. 1801 older adults who attended senior citizen clubs organized by
      local hospitals from 66 provinces of Thailand. RESULTS: 28.1% of subjects had
      been admitted to a hospital. Independent factors determining hospital admission
      were lung disease (adjusted OR 2.13), history of fall (adjusted OR 1.73), poor
      global self-rated health (adjusted OR 1.62), taking calcium tablets (adjusted OR
      1.61), preferring fatty food (adjusted OR 1.59), being former smokers (adjusted
      OR 1.56), low body mass index (adjusted OR 1.52), hypertension (adjusted OR 1.37)
      and poor mobility ability (adjusted OR 1.16). CONCLUSION: Prevention of hospital
      admission among the elderly should involve preventing cigarette smoking,
      promoting healthy dietary habit, fall prevention and screening for hypertension.

PMID- 16404832
TI  - Multiplex methylation specific PCR analysis of fragile X syndrome: experience in
      Songklanagarind Hospital.
AB  - Methylation specific PCR (MS-PCR) is a technology for a sensitive detection of
      methylation in the gene. This assay was developed for diagnosis of methylation
      related diseases including fragile X syndrome (FXS), the most common X-linked
      mental retardation caused by a CGG trinucleotide repeat expansion. Affected
      individuals (full mutation, FM) have CGG greater than 200 repeats, while normal
      individuals and premutation (PM) carriers have 6-54 and 55-200 repeats,
      respectively. Only FM individuals are correlated with methylation of the gene.
      The authors tested this assay on known 35 DNA samples (15 normal, 2 PM and 18 FM)
      and a prospective study of 60 males referred for FXS screening in Songklanagarind
      hospital. In addition, the authors tested on 2 prenatal cases. All results were
      corresponded to PCR for CGG repeats and/ or Southern blot analysis. The authors
      concluded that MS-PCR provides an accurate method for methylation detection of
      FXS.

PMID- 16404833
TI  - Quality of life of children with attention-deficit/hyper activity disorder.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has an impact on
      children and families. The purpose of this study was to assess the health-related
      quality of life between school-age children with ADHD compared with those without
      physical or mental disorders. MATERIAL AND METHOD: Self- and parent-reports
      describing the quality of life, covering 4 domains: physical, emotional, social,
      and school functioning, were obtained from 46 children with ADHD and 94 control
      children. At the time of the study, 17 of 46 children reported receiving
      medication for ADHD. RESULTS: After controlling for age and demographic
      background, both children with ADHD and their parents reported having a
      significantly lower quality of life score than controls and their parents.
      Children with ADHD also reported themselves to have a significantly low physical
      score, despite their physically healthy status. CONCLUSION: Children with ADHD
      had impairment of their quality of life in the physical and psychosocial domains.
      Improvement of health-related quality of life should be integrated in the overall
      planning of the treatment goals.

PMID- 16404834
TI  - The development of the Thai Psychiatric Satisfaction Scale.
AB  - BACKGROUND: Satisfaction with mental services is an important quality and outcome
      variable. The Thai Psychiatric Satisfaction Scale (TPSS) is developed in order to
      measure service satisfaction. OBJECTIVE: The purpose of the present study was to
      develop the Thai Psychiatric Satisfaction Scale (TPSS), having adequate and
      sufficient validity and reliability. MATERIAL AND METHOD: A sample of people with
      mental illness in the Department of Psychiatry, Siriraj Hospital was assessed.
      The TPSS was administered. Then factor analysis, internal consistency and test
      retest reliability were analized. RESULTS: The Thai Psychiatric Satisfaction
      Scale (TPSS) contains seven domains: Professionals' Skills and Behavior,
      Information, Access, Efficacy, Type of Intervention, Relative's Involvement, and
      Environment and Setting. The infinity coefficient for the TPSS was 0.97 (95% CI
      0.94-0.97) and ranged from 0.70 (95% CI 0.68-0.76) to 0.96 (95% CI 0.94-0.97).
      Test-retest for TPSS was 0.82. (95% CI 0.78-0.85). CONCLUSION: This TPSS is a
      validated and reliable multi-dimensional scale which measures the satisfaction of
      patients with mental health services for routine clinical practice in mental
      health service.

PMID- 16404835
TI  - Factors influencing outcome after hepatic portoenterostomy for biliary atresia: a
      logistic regression analysis.
AB  - BACKGROUND/OBJECTIVE: The association of many factors with the outcome in Biliary
      atresia (BA) after hepatic portoenterostomy has drawn the attention of many
      pediatric hepatologists and hepatobiliary surgeons. Understanding these factors
      will become an important subject in prediction of the postoperative status and in
      indicating further proper management. MATERIAL AND METHOD: During the last 9
      years, 159 BA babies were treated by hepatic portoenterostomy. The authors
      reviewed the following factors and how they related to outcome: age at operation,
      total bilirubin (TB) level, type of BA, postoperative bile drainage, hepatic
      histological features at operation, preoperative and postoperative cholangitis. A
      multiple logistic regression analysis was used to indicate the factors which
      significantly influenced the outcome. RESULTS: Of the 159 BA babies, clearing of
      jaundice confirmed by the color of stool and postoperative serum bilirubin level
      less than 2 mg % was observed in 54 patients (Group A). Bile drainage with mild
      jaundice (TB 2-5 mg %) was detected in 65 patients (Group B). The operation
      failed to create bile flow clinically and biochemically in 40 patients (Group C).
      Some patients in the last group died during follow-up due to hepatic disease. The
      multiple logistic regression analysis revealed that the age at operation (> 8
      weeks of age), and the presence of portal and parenchymal inflammation at
      operation significantly related to the failure of portoenterostomy which was
      followed by portal hypertension with or without esophageal varices. The presence
      of cholangitis was also significantly related to a poor outcome. CONCLUSION: The
      age at operation, portal and parenchymal inflammation and the presence of
      cholangitis are significant factors which relate to the poor prognosis of BA.
      Recognition of these will lead to proper long-term management.

PMID- 16404836
TI  - Extra charge and extra length of postoperative stay attributable to surgical site
      infection in six selected operations.
AB  - BACKGROUND: Information concerning the economic impact of surgical site infection
      (SSI) is very rare in Thailand. As the national health care financial system has
      been changing, the need for such data is critical. OBJECTIVE: The purpose of this
      study is to estimate the extra charge and excess postoperative hospitalization
      attributable to SSI in six surgical operative procedures comprising appendectomy,
      herniorrhaphy, mastectomy, cholecystectomy, colectomy, and craniotomy. MATERIAL
      AND METHOD: The study population consisted of patients undergoing major
      operations admitted to Songklanagarind Hospital from January, 1998 to December,
      2003. Data were prospectively collected to identify demographic data, surgical
      operations, development of SSI, and outcomes of SSI. The study used one-to-one
      matched-pair strategy to compare case (patient with SSI) and controls (patient
      without SSI). The matching criteria were same final diagnosis, same operative
      procedure, and same American Society of Anesthesiologists (ASA) score. Data were
      calculated for mean difference, median difference, and 95% confidence intervals
      (95% C.I) of hospital charge and postoperative stay. RESULTS: The study could
      identify 140 matched-pairs of case and control. When compared to matched
      controls, cases had higher hospital charge and greater postoperative length of
      stay. Mean of extra hospital charge attributable to SSI was 43,658 (95% C.I;
      30,228-57,088) baht and mean of excess postoperative stay was 21.3 (95% C.I; 16.6
      26.0) days. Median of extra expenditure was 31,140 (95% CI; 17,327-49,081) baht
      and median of prolongation of postoperative stay was 14 (95% C.I, 12-18) days.
      CONCLUSION: This study supports the findings of the previous published reports
      that patients who have SSI incur enormous excess cost and hospital stay.

PMID- 16404837
TI  - Prevalence of dyslipidemia in rural Thai adults: an epidemiologic study in Khon
      Kaen province.
AB  - Dyslipidemia is an important, modifiable CHD risk factor. Previous studies have
      reported the prevalence of dyslipidemia particularly in urban populations.
      However, its prevalence in rural Northeast Thailand has not been well documented
      since extensive dietary and lifestyle transitions induced by the rapid socio
      economic development of the late 1990s and early 2000s. The authors, therefore,
      conducted a cross-sectional assessment for the prevalence of dyslipidemia among
      rural Thais (in Khon Kaen province) using the National Cholesterol Education
      Program (NCEP) Adult Treatment Panel (ATP III) Guidelines. The 325 subjects
      recruited (136 men; 189 women) averaged 53.8 +/- 17.6 years of age (range, 20
      88). After having the subjects fast 12 hours, serum samples were collected. Total
      cholesterol, triglycerides, low-density lipoprotein (LDL-C) and high-density
      lipoprotein (HDL-C) cholesterols were measured. The prevalence of
      hypercholesterolemia (> 200 mg/dL), hypertriglyceridemia (> 150 mg/dL), high LDL
      C (> 130 mg/dL) and low HDL-C (< 40 mg/dL) was 31, 40, 20 and 14 per cent,
      respectively. Women had a 2- to 3.5-fold higher prevalence of
      hypercholesterolemia and high LDL-C than men, while the prevalence of
      hypertriglyceridemia was comparable. The prevalence of dyslipidemia increased
      with advancing age and increasing BMI; notwithstanding, a high prevalence of
      dyslipidemia was observed in the youngest tertile as well. In conclusion, the
      present study demonstrated a high prevalence of dyslipidemia in rural Thai
      adults; consequently, primary lipid screening should be considered for all ages.

PMID- 16404838
TI  - Comparison of leptospiral serovars identification by serology and cultivation in
      northeastern region, Thailand.
AB  - Blood from patients suspected of leptospirosis 148 specimens were cultured for
      leptospira. Twenty two specimens were positive (15%). The isolated leptospira
      were tested against the 24 serovars of standard antisera by Microscopic
      Agglutination Test (MAT). It was found that all 22 leptospira isolates reacted
      strongly against L. autumnalis, except 1 isolate that also reacted against
      serovar djasiman. The patient's sera were collected from only 14 cases. When the
      sera of the 14 patients were tested with the 24 reference serovars by MAT it was
      found that sera reacted the most against L. australis and in decreasing order
      against L. bratislava, L. autumnalis, L. rachmati, L. copenhageni, L. javanica.
      There had some cross reactions against several serovars in a single patient. The
      present study showed inconsistency between culture results and serum assays.
      Since sera showed cross reactivities against several serovars, it was not
      possible to determine which serovar was etiologic. Therefore, the isolation of
      leptospira though time consuming is specific in the identification of the
      serovar.

PMID- 16404839
TI  - Risk factors and techniques affecting surgical outcome of therapeutic endoscopic
      retrograde cholangiopancreatography difficulties.
AB  - OBJECTIVE: To analyze the therapeutic endoscopic retrograde
      cholangiopancreatography (ERCP) difficulties and complications experienced by a
      general surgeon and identify risk factors and technique affecting surgical
      outcome. MATERIAL AND METHOD: A retrospective review was carried out in 88
      consecutive ERCP operated with four different indications on patients in
      Nakornping General Hospital by a surgeon trained from Nippon Medical School,
      Japan. RESULTS: The patients average age was 57.2 years. Fifty-four patients had
      common bile duct stone and 43 of them were successfully removed. Endoscopic
      sphincterotomy (EST) was the most frequent procedure needed to combine with the
      stone extraction (23 in 43). Twenty-two distal common bile duct obstructions
      unable to be diagnosed by ultrasound or computed tomography were operated on and
      found to be unvarying proportion of tumor, stone or stricture. Among these 6
      biopsy and 12 treatments were concurrently made. Eight bile fistula and four
      cholangitis were indicated for endoscopic drainage. Only one serious bleeding was
      complicated. Two perforations were discovered in the present series and none
      required laparotomy repair of duodenum. Eighteen of the 88 failed to be operated
      on and most of them were within first four-month learning curve. Duodenal
      diverticulum was a common failure factor. The pre-procedure unknown diagnosis
      relates to an insignificant risk 2.4 times complications of the known (RR = 2.4,
      p = 0.31). Three patients (3.4%), all over 70 years old, succumbed late after
      ERCP due to sepsis and myocardial infarction, compared to those age under 70 is a
      significant risk factor (p = 0.059). Age over 50 seems to result in a higher
      pancreatitis complication (3 versus none under 50) but not statistically
      significant (p = 0.405). CONCLUSION: Skill and synchronous assistance are
      important factors for success of ERCP but a more unpredictable outcome and
      complications were encountered for the preoperative undiagnosable obstructive
      jaundice. Hot and slow sphincterotomy would minimize the bleeding complication.
      Duodenal diverticulum and those operated on for late obstruction were risk
      factors in patients with EST perforations. Pondering to be minimally by invasive,
      advanced age still contributes to a higher complication and mortality risk in the
      surgical treatment of ERCP.

PMID- 16404840
TI  - Clinical response of depressive patients in a Thai psychiatric care setting.
AB  - OBJECTIVE: To obtain data on the clinical outcome of patients with depressive
      disorders after three months psychiatric care in a Thai psychiatric unit.
      MATERIAL AND METHOD: A prospective descriptive study of 96 patients followed up
      for 3 months. The severity of depression was measured with the Thai version of
      the Hamilton rating scale for depression (HAM-D Thai). RESULTS: The response rate
      following 3-months psychiatric care was 67.7% (95% CI = 58.18-77.23). Fifty
      percent of the patients had a HAM-D Thai score of < 7 at week 12. CONCLUSION: The
      treatment outcome in the Thai psychiatric setting described is comparable to that
      reported in other countries.

PMID- 16404841
TI  - Preoperative portal vein embolization in hepatobiliary tract malignancy: an
      experience at King Chulalongkorn Memorial Hospital.
AB  - BACKGROUND: Major hepatic resections are increasingly performed for both primary
      and secondary liver cancers nowadays. However, morbidity from these operations is
      still high. One of the dreadful complications, sometimes lead to fatality, is
      postoperative liver failure. There are many factors which are associated with
      this complication such as chronic liver disease, low residual liver volume after
      resection. Portal vein embolization (PVE) is the procedure which increases the
      liver volume of the non-embolized lobe. Now, PVE has gained acceptance in many
      centers to overcome or reduce this complication. This report described the
      authors' experiences of PVE since 2001 at King Chulalongkorn Memorial Hospital.
      MATERIAL AND METHOD: The records of 10 patients who had PVE were reviewed CT
      volumetry of the liver was done before and after procedure. The authors
      calculated future liver remnant from CT volumetry and compared this volume to
      standard liver volume. The postoperative complications and hospital courses of
      these patients were also recorded. RESULTS: Mean growth of future liver remnant
      (FLR) ratio after PVE was 13.7 +/- 6.2% (median 13, range 4-25). There was no
      major complication after PVE. Six patients underwent liver resection and there
      was no major complication or mortality. No one had persistent hyperbilirubinemia
      2 weeks after operation. CONCLUSION: The PVE is the useful and safe optional
      procedure to increase future liver remnant volume. It not only reduces the
      postoperative liver failure but increases the chance for curative resection.

PMID- 16404842
TI  - Case report of voiding difficulty after intravaginal slingplasty (IVS) procedure:
      the emphasize of pre-service training.
AB  - BACKGROUND: The Intravaginal slingplasty procedure (IVS) is a minimally invasive
      surgery for the treatment of stress urinary incontinence (SUI). Too much tension
      during pulling the tape and the incorrect placing of the tape can cause urinary
      retention that may require release of the tape. CASE REPORT: A fifty one years
      old women with SUI had undergone IVS procedure in a private hospital. After the
      surgery, urinary retention occurred with prolonged catheterization for 20 days.
      The patient came to King Chulalongkorn Memorial Hospital on the 21st day after
      the operation. Surgical release of the tape which was located at the
      urethrovesical junction rather than the midurethera was done. The patient
      remained stress continent after the tape was released confirmed by the
      videourodynamic study one month later. CONCLUSION: Too much tension, insertion of
      the tape too close to the urethrovesical junction or the tape migration may be
      the causes of prolonged urinary retention after IVS procedure. The authors found
      the surgical release of the tape to be the effective management for this
      complication. Pre-service training in models and practice under the supervision
      of an experienced surgeon are needed before attempting any on their own. From the
      authors extensive review, this is the first case report of urinary retention
      after IVS procedure that required tape incision.

PMID- 16404843
TI  - Incomplete duplication of the esophagus: a case report.
AB  - A case of incomplete duplication of the esophagus diagnosed in a 20-month-old
      girl with an esophageal perforation is presented. X-ray films of the chest showed
      pneumomediastinum and subcutaneous emphysema. A water soluble contrast
      esophagogram revealed a contrast leakage from the cervical esophagus to the
      thoracic inlet. The endoscopic findings are described. Complete resection of the
      esophageal duplication was effective.

PMID- 16404844
TI  - Anorectal malignant melanoma: report of two cases from Buddhachinnaraj Hospital.
AB  - Anorectal malignant melanoma is a rare disease and has a uniformly poor
      prognosis. The following are two reported cases from Buddhachinaraj Hospital. A
      55-year-old and a 65-year-old female patients presented with rectal bleeding.
      Large anorectal masses with regional lymph node involvement were detected
      initially. They exhibited different histological features which were atypical
      round cell resembling lymphocytes or were small cell appearance and spindle cell
      appearance similar to sarcoma. The diagnosis was confirmed by expression of S100
      protein and HMB45. Abdominoperineal resection (APR) was the treatment of choice
      in both patients. The former case died in the fourth month after diagnosis
      because of distance metastasis and congestive heart failure. The latter case is
      receiving postoperative adjuvant therapy.

PMID- 16404845
TI  - Choroidal detachment after topical prostaglandin analogs: case report.
AB  - OBJECTIVE: To report three cases of delayed choroidal detachment after treatment
      with topical prostaglandin analogs. MATERIAL AND METHOD: Intervention three case
      reports. Four eyes of three patients with chronic angle closure glaucoma
      developed choroidal detachment after using topical prostaglandin analogs.
      RESULTS: Three patients with chronic angle closure glaucoma developed chroidal
      detachment in one week, three weeks and two years after using travoprost,
      bimatoprost and latanoprost respectively. All of them resolved after
      discontinuation of these medications. All of the eyes that developed chroidal
      detachment were pseudophakic. CONCLUSION: Travoprost, bimatoprost and latanoprost
      may lead to choroidal detachment and hypotony. Pseudophakic patients may be at
      high risk of the development of chroidal detachment. Topical prostaglandin
      analogs should be used cautiously in these patients.

PMID- 16404846
TI  - Unruptured left cornual pregnancy: case report.
AB  - Cornual pregnancy is a rare condition. The morbidity and mortality are directly
      related to the length of time for diagnosis. The present paper reports a case of
      unruptured left cornual pregnancy which was diagnosed by the patient's symptom,
      physical examination and positive urine pregnancy test. Ultrasonography confirmed
      the diagnosis. Left cornual resection was carried out in the present case without
      immediate or long-term complication.

PMID- 16404847
TI  - Ternidens deminutus infection: first pathological report of a human case in Asia.
AB  - This is a report of Ternidens deminutus infection in a 33 year old Thai female
      who was admitted to the hospital because of abdominal pain and a right lower
      quadrant mass. Exploratory laparotomy revealed an omental mass with attached
      terminal ileum. Resection of the mass together with the terminal ileum and the
      right sided colon was performed. Pathologically, the omental mass was an abscess
      with an immature male Ternidens deminutus identified. The parasite usually is
      found in the intestine of primates in Africa and Asia. Human infection occurs
      when food contaminated with infective filariform larvae is ingested. The larvae
      molt in the intestinal wall and become adults. They pass eggs in feces. Eggs in
      contaminated soil hatch and become rhabditiform larvae and then infective
      filariform larvae.

PMID- 16404848
TI  - Computer based program for rapid canine rabies diagnosis.
AB  - Rabies post exposure treatment and rapid diagnosis in an endemic area requires
      skillful and an experienced medical staff and veterinary specialists. A software
      program was introduced in 2000 as a tool to diagnose rabies based on clinical
      symptoms and signs of suspicious dogs where veterinarian service and other
      laboratory diagnostic options are not immediately available. It is easily
      accessed from the website: www.soonak.com/rabies.

PMID- 16404849
TI  - Overview in pediatric hematopoietic stem cell transplantation.

PMID- 16404851
TI  - What is your opinion on the "medical ethics of medical journal editors"?

PMID- 16404852
TI  - [Infectious diseases: a global challenge and problem of military medicine].

PMID- 16404850
TI  - Rapidly growing mycobacteria in King Chulalongkorn Memorial Hospital and review
      of the literature in Thailand.
AB  - Rapidly growing mycobacteria (RGM) have emerged as important human pathogens that
      can cause a variety of diseases. Thirty isolates of the pathogenic RGM were
      recovered from patients who attended King Chulalongkorn Memorial Hospital during
      1997 and 2003. There were 16 isolates of Mycobacterium chelonae, ten isolates of
      M. fortuitum and four isolates of M. abscessus. Clinical data was available in
      only nine patients (five males and four females) including six M. chelonae, two
      M. abscessus, and one M. fortuitum. The mean age was 37 years (range: 13-62
      years). The associated conditions were present in five patients including two
      diabetes, one HIV infection, one pregnancy, one SLE and one chronic renal
      failure. A wide spectrum of clinical features was observed. These included two
      chronic pulmonary infections, two post-traumatic wound infections, two
      disseminated infections, one lymphadenitis, one keratitis and respiratory
      colonization. AFB staining was positive in six patients (66.67%). The MIC of one
      M. chelonae and one M. abscessus were determined by Epsilon test. For M.
      chelonae, the MIC of clarithromycin, amikacin, ciprofloxacin, sulfamethoxazole
      and imipenem were 0.25, 2.0, 1.00, > 64, and 0.54 microg/ml, respectively. For M.
      abscessus, the MIC of clarithromycin, amikacin, ciprofloxacin, tetracycline and
      sulfamethoxazole were 0.016, 0.016, 0.038, > 16 and 0.002 microg/ml,
      respectively. Six of eight patients (75%) were initially treated with four first
      line antituberculous drugs (isoniazid, rifampicin, pyrazinamide and ethambutol)
      before obtaining the culture result. Of these, three patients with pulmonary and
      disseminated infections improved after a prolonged course of these combinations.
      The patients improved after switching to specific anti-RGM antibiotics. One
      patient died after 10 months of therapy of four anti-tuberculous drugs. One
      patient with post-traumatic wound infection was cured with surgical debridement
      and dicloxacillin. One patient improved after treatment as acute bronchitis with
      oral amoxicillin. An extensive review of the literature of RGM infections in
      Thailand is also presented.

PMID- 16404853
TI  - [Development of immunopathology in patients with yersinia infection].
AB  - AIM: To evaluate clinical significance of changes in IL-6 concentration and
      neopterin in peripheral blood of patients for prognosis of the course and outcome
      of yersinia infection (YI). MATERIAL AND METHODS: Clinical examination and
      laboratory tests, 1-5-year follow-up were conducted in 68 patients with a cyclic,
      recurrent and lingering course of the disease. IL-6 and neopterin concentrations
      were measured in the course of the disease. RESULTS: Dynamic control over IL-6
      concentrations in the blood of patients with yersinia infection provides
      information predicting the disease course and prognosis. Blood concentrations of
      neopterin are of help in prognostication of long-term outcomes of acute
      infection. CONCLUSION: Pathological syndromes forming in acute stage of yersinia
      infection are related to interleukin-dependent immunopathology.

PMID- 16404854
TI  - [Invasive streptococcal (group A) infection: an overview].

PMID- 16404855
TI  - [Cytomegalovirus infection of the gastrointestinal tract in patients with HIV
      infection].
AB  - AIM: To study clinical and morphological characteristics of gastrointestinal
      cytomegalovirus (CMV) infection in HIV-infected subjects. MATERIAL AND METHODS:
      The examination of 70 HIV-infected subjects (all of them had secondary diseases,
      AIDS, CMV infection in the gastrointestinal tract; mean age 31.2 +/- 1.4 years)
      observed from 1993-2005 included conduction of flow cytofluorimetry (to assess
      immunity), esophagogastroduodenoscopy, colonoscopy, PCR (to assay CMV DNA in
      blood leukocytes), examination of biopsy and autopsy samples for CMV DNA and
      other pathogens of opportunistic diseases). There were 55 lethal outcomes. In
      autopsy, a total macroscopic and microscopic examination of the gastrointestinal
      tract was made. Serial histotopographic sections were studied with a wide
      spectrum of histological stains. RESULTS: CMV gastrointestinal lesion was
      diagnosed in 38.9% of 180 HIV-infected subjects who had stomatitis, pharyngitis,
      esophagitis, gastritis, enteritis, enterocolitis or colitis. Diagnostic criteria
      of viral lesion were high blood concentrations of CMV DNA, the presence of
      cytomegalocells, CMV DNA in biopsy or autopsy material. CONCLUSION: CMV infection
      manifested with severe pain, loss of weight, weakness, remitting fever.
      Gastrointestinal lesions were erosive-ulcerous or ulceronecrotic. The following
      pathogenetic chain of CMV infection course in the gastrointestinal tract was
      established: vasculitis--microcirculatory disorders--segmental ischemia--necrosis
      with inflammatory infiltration and CMV transformation of the cells--fibrosing-
      cicatricial transformation of the organ wall. Developing sclerosis due to CMV
      involvement of the intestine may promote cancer, but this should be proved in
      further studies. CMV gastrointestinal infection was successfully treated by
      cimeven (ganciclovir) and valcit (valganciclovir). The effect was achieved in 91%
      cases.

PMID- 16404856
TI  - [Pneumocystic pneumonia in combination with tuberculosis as initial clinical
      symptoms in late HIV-infection].

PMID- 16404857
TI  - [Cytokine regulation of immune response in patients with acute HCV-infection].
AB  - AIM: To study the cytokine spectrum (IL-1beta, IL-2, IL-4, IL-6, TNF-alpha,
      interferon-alpha, interferon gamma) in patients with acute hepatitis C (AHC).
      MATERIAL AND METHODS: Peripheral blood from 70 AHC patients was studied for
      cytokines using enzyme immunoassay (kits made by Protein contur, St-Petersburg).
      RESULTS. A primary examination in all the patients who finally recovered detected
      high levels of IL-2, IL-6, interferon-gamma, normal levels of IL-4. This
      evidenced for marked activity of Th1-lymphocytes, depressed synthesis of Th2
      mediators stimulating immune response and elimination of the virus. AHC patients
      who later developed chronic disease had less frequent rise of proinflammatory
      mediators, but more frequent high IL-4 levels. Such features of immune response
      reflected higher activity of Th2-lymphocytes inhibiting Th1-effector mechanisms.
      This promoted active virus replication and formation of chronic hepatitis C.
      CONCLUSION: Determination of cytokine spectrum in AHC has a prognostic
      implication.

PMID- 16404858
TI  - [Assessment of efficacy of the drug litovit as a novel pathogenetic modality in
      acute virus hepatitis].
AB  - AIM: To study clinical and laboratory parameters in patients with acute viral
      hepatitis (AVH) given basic therapy in combination with a novel pathogenetic drug
      litovit versus ursosan. MATERIAL AND METHODS: 155 patients with AVH were divided
      into three groups: 70 patients of group 1 received basic therapy plus litovit, 10
      patients of group 2--basic therapy plus ursosan, 60 patients of group 3--basic
      treatment only. RESULTS: Litovit was well tolerated. Side effects were absent.
      Hospital stay and severity of clinical AVH symptoms were significantly less in
      patients of group 1. Less pronounced were also hyperbilirubinemia, cytolytic and
      mesenchymal-inflammatory syndromes. CONCLUSION: Clinical and laboratory
      parameters in AVH patients treated with adjuvant litovit improve quicker than in
      those with adjuvant ursosan or basic therapy. Litovit has enterosorptive and
      hepatoprotective activity. Low cost of vitovit therapy makes the drug applicable
      in wide practice.

PMID- 16404859
TI  - [Immune status of patients with different outcomes of acute hepatitis C].
AB  - AIM: To ascertain parameters of immune response significant for prognosis of the
      disease outcome in patients with acute hepatitis C (AHC). MATERIAL AND METHODS:
      Seventy two examinees were divided into three groups: 30 patients of group 1 had
      AHC; 29 patients of group 2 had chronic hepatitis C (CHC) with the disease
      history 3-10 years; 13 AHC convalescents who had the disease 3-10 years ago. The
      control group consisted of 10 healthy subjects. The following parameters of
      immune status were studied: CD3+, CD4+, CD8+, CD16+, CD20+, HLA-DR+CD3+, CD95+, O
      lymphocytes. RESULTS: By clinicobiochemical picture and the results of 12-month
      follow-up RT-PCR investigations of blood HCV RNA, AHC patients were divided into
      two groups: in 18 (72%) of 25 patients AHC became chronic, 7 (28%) patients
      achieved convalescence. The proportion and absolute number of subpopulations of
      lymphocytes CD8+, CD20+, CD16+ as well as CD4/CD8 in patients with AHC with
      different outcomes did not differ from the controls. AHC convalescents and
      patients with AHC transformation into chronic hepatitis had in the acute period
      of the disease much higher absolute number of subpopulations of the lymphocytes
      CD3+, CD4+, HLA-DR+CD3+ vs the controls. In patients with chronic hepatitis C
      with elevated levels of AlAT, 3-10 year follow-up registered significantly higher
      absolute amount of CD8+, CD3+, CD4+, HLA-DR+CD3+ vs the controls. Only patients
      with AHC which later became chronic had for 6 months of the disease significantly
      elevated absolute number of O-lymphocytes vs the controls. CONCLUSION: A high
      absolute count of O-lymphocytes in AHC patients may indicate probable development
      of chronic hepatitis C.

PMID- 16404860
TI  - [Cyclopheron pretreatment in opisthorchiasis management in patients with viral
      hepatitis C].
AB  - AIM: To assess efficacy of cyclopheron (Polysan production) as opisthorchiasis
      pretreatment in patients with chronic viral hepatitis C (CHC). MATERIAL AND
      METHODS: Fifteen CHC patients received cyclopheron by 6 month scheme before
      dehelminthization. The effect was evaluated by dynamics of clinical symptoms,
      results of functional hepatic tests, levels of autoantibodies to antigens of
      native and denaturated DNA, CIC and lactoferrin. Fourteen control patients did
      not receive pretreatment with cyclopheron. RESULTS: The study group patients
      exhibited a relief of asthenovegetative and pain syndromes, aminotranspherases
      lowered to normal in 11 patients, minimal activity of cytolytic syndrome--in 4
      patients. Lactoferrin normalized in all the patients, coefficient of
      autoantibodies to antigens of native and denaturated DNA fell two-fold. No
      significant improvement in the clinical and laboratory picture was seen in the
      controls. CONCLUSION: Cyclopheron in patients with CHC combination with chronic
      opisthorchiasis is recommended as pretreatment before dehelminthization.

PMID- 16404861
TI  - [Septic diseases--sepsis: treatment].

PMID- 16404862
TI  - [The course of chronic glomerulonephritis in chronic opisthorchiasis].
AB  - AIM: To characterize clinical, functional and morphological features of chronic
      glomerulonephritis (CGN) running with chronic opisthorchiasis (CO) and to justify
      dehelminthization. MATERIAL AND METHODS: Clinical, functional and morphological
      examinations of the kidneys, immunological characteristics were studied in 100
      patients with primary CGN and CO (group 1), 30 patients with CGN free of CO
      (group 2) and 40 patients with long-term CO. RESULTS: CGN in CO runs with
      frequent rise of creatinine, glomerular filtration and canal reabsorption fall.
      Pathogenetic therapy with addition of pulse cyclophosphamide in a dose 10 mg/kg
      and conduction of dehelminthization a year later lead to long-term remission and
      inhibition of nephrosclerosis development. CONCLUSION: Clinicofunctional and
      morphological characteristics of the kidneys in mixed pathology necessitate
      addition of immunosuppressor cyclophosphamide in a dose 10 mg/kg and
      dehelminthization in combined treatment of patients with glomerulonephritis and
      opisthorchiasis.

PMID- 16404863
TI  - [Clinical and cost-effect results of the activity of the outpatient "Hypertensive
      Patient School"].
AB  - AIM: To analyse clinical and cost efficacy of 6-year (1999-2005) activity of the
      outpatient "Hypertensive Patient School" (HPS) at the consultative and diagnostic
      center N 52 of the RF Ministry of Defense. MATERIAL AND METHODS: A total of 232
      hypertensive patients followed up for 2 years were divided into two groups: 120
      patients of group 1 participated in the education antihypertensive program at HPS
      and received combined therapy according to chrono = pharmacology; 112 patients
      did not attend the HPS and were treated conventionally. RESULTS: The lectures at
      HPS raised awareness of the patients about their disease and its risk factors
      from 45.8 to 100% (p < 0.05), compliance from 71.7 to 99.2% (p < 0.001),
      treatment adequacy from 15.8 to 88.3% (p < 0.01), improved quality of life from
      13.3 to 95.0% (p < 0.001), finally resulting in reduction of hypertensive crises
      and hospitalizations from 32.5 to 2.5% (p < 0.01), side effects frequency from
      30.8 to 3.3% (p < 0.05). The cost of outpatient management of one patient fell by
      3661.0 roubles. CONCLUSION: Learning at HPS prevents complications of essential
      hypertension, promotes adequate control over systolic and diastolic pressure,
      improves quality of life, raises cost efficacy of the disease therapy.

PMID- 16404864
TI  - [Anxiodepressive and neuromediatory disorders in hypertensive patients. Effects
      of cypramil therapy].
AB  - AIM: To investigate psychic status and characteristics of neuromediatory
      metabolism in hypertensive patients, efficacy of antihypertensive therapy with
      lisinopril and hydrochlorthiaside with adjuvant citalopram (cipramil) which is a
      selective inhibitor of serotonin reuptake. MATERIAL AND METHODS: Fifty patients
      with hypertension stage II (37 females, 13 males, mean age 48 years, mean
      duration of the disease 10.6 years) have undergone psychometric examination,
      estimation of evoked potentials P-300, 24-h monitoring of blood pressure. Plasma
      levels of epinephrine and norepinephrine, plasma and platelet levels of serotonin
      and 5-OIAA were measured at high-performance liquid chromatography. RESULTS:
      Hypertensive patients were found to have high levels of depression, reactive and
      personality anxiety, subnormal quality of life. Blood pressure lowered more in
      patients given adjuvant cipramil. CONCLUSION: Hypertensive patients have
      anxiodepressive disorders accompanied by monoamines disbolism. Cipramil
      effectively corrects these disorders.

PMID- 16404866
TI  - [Combined medication ARTRA in the treatment of osteoarthrosis].
AB  - AIM: To study clinical effectiveness, safety and duration of the effect of
      combined medication ARTRA (500 mg glucosamine hydrochloride+500 mg chondroitine
      sulphate) in osteoarthrosis. MATERIAL AND METHODS: Ninety women aged 40-75
      suffering from knee OA and satisfying diagnostic criteria for OA of American
      Rheumatological Committee having x-ray II-III stages according to Kellgren
      Lawrence; with distinct pain syndrome (pain intensity at walking 40 mm and more
      by the analogue visual scale); taking NSAIDS regularly during 30 days within 3
      months before the study were enrolled in the study. The patients were randomly
      divided into 2 groups: 45 patients of the study group taking 1 tablet ARTRA 2
      times a day within the first month, than 1 tablet a day within the following 5
      months and diclofenac sodium 50 mg 2 times a day with gradual decrease of the
      dosage as the pain was decreasing; 45 patients of the control group taking only
      diclofenac sodium 50 mg twice a day during 6 months. Clinical examination of the
      patients was done before the treatment, 30, 120 and 180 days after the study.
      Long-term effects of ARTRA was evaluated 3 months after the study. The treatment
      efficacy was assessed by WOMAC index, daily need in NSAIDS intake, evaluation of
      the efficacy by the patient and the doctor. RESULTS: The true WOMAC index
      decreased in 4 and 6 months of therapy in the study group (p < 0.03). 3 months
      after the treatment the study group patients experienced continuous reduction of
      the functional index and pain intensity unlike of the control patients
      experiencing a pain increase and worsening of joints functional ability. When
      analysing pain syndrome according to VAS, after 4 months of the treatment pain
      was relieved more in the study group (p = 0.008). The differences were stable for
      6 months. On aftertreatment month 3 pain syndrome tended to attenuation in the
      study group but to intensification in the controls. While taking ARTRA, the
      patients decreased their need in NSAIDS intake (diclofenac). After 1 month of
      therapy 4.5% patients gave up taking diclofenac; after 4--20%, after 6--40%.
      Objective and subjective effects did not differ much (94 and 90%, respectively).
      ARTRA tolerability was very good. None of the patients of the study group
      discontinued therapy because of side effects, in the control group 14 patients
      gave up diclofenac because of the adverse effects. CONCLUSION: Combined ARTRA
      medication decreases pain, improves joint function. Regular intake of ARTRA helps
      decrease NSAIDS dosage or discontinue intake in many cases. ARTRA is very well
      tolerated and is safe. ARTRA has an evident long lasting effect.

PMID- 16404865
TI  - [Nitric oxide and cardiac failure].
AB  - AIM: To study the synthesis of nitric oxide II (NO) in patients with acute
      myocardial infarction (AMI) and patients with postinfarction cardiosclerosis
      (PICS) with chronic cardiac failure (CCF). MATERIAL AND METHODS: The study
      included 125 patients: 35 patients with Q-wave AMI and 90 PICS patients. AMI
      patients were examined clinically, device and laboratory tests were made to
      measure NO metabolites in the urine, plasma, culture medium of peripheral blood
      mononuclear cells on MI day 1 and 21, iNOS was estimated in mononuclear cells of
      peripheral blood on MI days 1, 2, 7, 14 and 21. PICS patients examination
      incorporated assays for NO metabolites in 24-h urine and plasma, in blood
      lymphocytes on MI day 1, 14 and 28.2 days before NO tests, all nutritional
      nitrates and nitrites were excluded from the diet. Control group consisted of 15
      nonsmokers aged 33 to 53 years (mean age 43.7 +/- 9.3 years). The level of NO
      metabolites in the urine was 49.7 mcM, in plasma--19.7 mcM, in lymphocyte culture
      -28.8 mcM. RESULTS: By urinary nitrites/nitrates all the MI examinees were
      divided into three subgroups: with low, moderate and high levels content of
      nitrites and nitrates (subgroups 1, 2 and 3, respectively). The correlation
      analysis has established significant correlations between NO metabolites in urine
      and plasma in the first MI hours and the data on the clinical status, device
      characteristics of myocardial lesion extention and prognosis of the disease. The
      most severe MI course and PICS was seen in subgroup 1, of moderate severity--in
      subgroup 3, a favourable course--in subgroup 2. CONCLUSION: Assay for nitrites
      and nitrates in the urine and plasma is necessary for selection of
      pathogenetically validated prescription of nitrates to AMI and PICS patients.

PMID- 16404867
TI  - [DNA-abzymes in rheumatoid arthritis: pathogenetic and clinical significance].
AB  - AIM: To study possible pathogenetic role and clinical significance of DNA
      hydrolysing autoantibodies (autoAB) or DNA-abzymes in patients with rheumatoid
      arthritis. MATERIAL AND METHODS: Prevalence of DNA-abzymes and their catalytic
      activity were studied in 400 patients with rheumatoid arthritis (RA) and 88
      healthy donors matched by age and gender. RESULTS: Associated with DNA-binding
      autoAB DNA-hydrolysing activity was detected in 41.5% cases of RA. DNA-abzymes
      were maximally active in men with rheumatoid factor (RF) and women without RF,
      while it was minimal in men without RF and women with RF. By catalytic activity
      there was no significant differences between patients with RF and without it. The
      highest catalytic activity of DNA abzymes was detected in patients with distinct
      extraarticular pathology. DNA-abzymes were also active in patients with x-ray
      stage III-IV of the disease in association with high prevalence of catalytic
      autoAB. DNA abzymes were also active in patients with RA activity stage II and
      III. CONCLUSION: It is possible to use DNA-abzymes in clinical practice for
      monitoring of the disease activity in RA.

PMID- 16404868
TI  - [Polyneuropathy as a manifestation of Churg-Strauss syndrome].

PMID- 16404869
TI  - [The role of inhalatory glucocorticosteroids in the treatment of chronic
      obstructive pulmonary disease].

PMID- 16404870
TI  - [Erectile dysfunction in patients with diabetes mellitus].

PMID- 16404871
TI  - [Xenobiotics in cigarettes: etiological stimulus of vascular lesion].

PMID- 16404872
TI  - [The integrating role of environmental medicine in the prevention, early
      diagnosis, and treatment of diseases associated with the influence of
      environmental factors].

PMID- 16404873
TI  - [Scientific and economic aspects of the solution of regional problems in
      environmental medicine].

PMID- 16404874
TI  - [Analysis of the perception of risk to health and the readiness to pay for its
      reduction].

PMID- 16404875
TI  - [Problems of epidemic safety of drinking water use by the population of Russia].
AB  - Quantitative relationships were studied between the indicators (common coliform
      bacteria (CCP), glucose-positive bacteria (GPB), thermoduric bacteria (TDB),
      coliform bacteria, enterococci, clostridia, coliphages) and the opportunistic
      (Pseudomonas aeruginosa, Proteus, Klebsiella) and pathogenetic (Salmonella and
      intestinal viruses) microorganisms at the stages of effluent purification and
      decontamination, in processes of self-purification in the water reservoirs and of
      water preparation at water-supplying stations, as well as in the association with
      the incidence of acute intestinal infections of bacterial and viral genesis in
      different climatic zones of the country. Salmonella and the opportunistic
      bacteria of the Enterobacteriaceae family and Pseudomonas aeruginosa were found
      to be highly resistant to detoxifying agents and environmental factors,
      adaptable, able to reproduce in pure water, to long survive in underground
      waters, and to accumulate when water is desalinated at the erections. The cases
      of intestinal infections were found in the population using the portable water of
      the standard quality in terms of E. coli, TDB, CCB, and enterococci. In this case
      only the wider integral index of GPB, which includes the indices of E. coli, TDB,
      CCB, as well as lactose-negative pathogenic and opportunistic species retains its
      sanitary significance in terms of all signs and is a reliable indicator of the
      potential epidemic hazard of drinking water use. Long-term studies have provided
      evidence for the sanitary value of coliphages as indicators of viral drinking
      water contamination.

PMID- 16404876
TI  - [Determination of the hazard of an enterprise and the width of its sanitary
      protective area by means of a nomogram].

PMID- 16404877
TI  - [A system for predicting the toxicity and hazard of chemical substances, based on
      the joint use of logistic and numerical methods].
AB  - A version of a logical combinatorial intellectual system (DMS system) has been
      developed to predict the toxicity and hazards of chemical substances. The system
      is based on the combined description of the substances, which includes both
      structural and numerical descriptors, particularly those characterizing the
      reactivity of compounds or their metabolites. The selection of numerical
      descriptors is based on the classification of processes of the interaction of the
      substance with the body in accordance with the key stage of the mechanism
      responsible for its toxic action. The new version of the DSM system takes into
      account the fact that the toxicity and hazard of chemicals are frequently
      determined by their bioactivation. Examples of how to apply the system to the
      prediction of carcinogenicity are given.

PMID- 16404878
TI  - [Problems in the assessment of carcinogenic risk of dioxins].

PMID- 16404879
TI  - [Structural and functional assessment of the body's status after consumption of
      the waters treated with various technologies].
AB  - The use of waters treated by different technologies was studied in animals and
      volunteers. Rats were used to study the use of the immunomodulated water "Renorm"
      alone and in combination with ozone-sorption treated Moscow tap water in a
      dilution of 1:10, that of the bottled water "Grander" (Austria) in combination
      with ozone-sorption treated Moscow tap water in a dilution of 1: 4 or 1:40; that
      of the water prepared by the Grander technology through a shower device when,
      after ozone-sorption purification, Moscow tap water was passed through a Grander
      shower device at a rate of 1 liter per min or 500 ml per 30 sec; that of the
      water electrochemically treated by an Izumrud (Emerald) installation. Moscow tap
      water served as a control for all waters and was Moscow dechlorinated water after
      ozone-sorption purification, by passing Moscow tap water from a tap into a 3
      liter vessel through a household ozone device for 5 min and then passing it
      through a household coal filter (500 ml). "Troitsa" water also served as a
      control for Renorm water and as the basis for the water physically treated. The
      nasal and oral cytological status was followed up in different periods (before
      and a month after water use and 1, 2, and 6 months following a monthly use) in
      different groups of volunteers: control and placebo groups, and in the groups of
      the examinees after using the waters treated by energy-informational technologies
      (Renorm), and by the Grander technology. Experimental studies have revealed that
      the consumption of the waters in question not merely fails to cause negative
      changes in the viscera, but also improves a number of structural and functional
      indices and, in the volunteers, the use of the waters treated by the energy
      informational technologies enhances the protective function of tissue barriers,
      such as the mucosae of the nose and mouth, by diminishing inflammatory reactions
      in these organs. Thus, both field and experimental studies have demonstrated that
      the use of the waters treated by different technologies results in structural and
      functional improvements.

PMID- 16404880
TI  - [Medical aspects of human health protection from the deleterious influence of
      environmental factors].

PMID- 16404881
TI  - [Catastrophe hygiene, its contents and place in the federal surveillance service
      system in the protection of consumers' rights and human well-being].
AB  - In the past two decades, there has been an increase in the number of earthquakes,
      tidal waves, accidents at chemically dangerous enterprises, and other types of
      catastrophes, which have posed an emergency survival problem for society. The
      scientific development of this problem has given rise to a new area of preventive
      medicine--catastrophe hygiene that is designed to eliminate (reduce) the poor
      influence of emergency factors and to offer the suffered population safe
      conditions of accommodation and/or life, water supply, nutrition, and other
      elements of survival under these conditions. The paper defines the subject and
      objects of studies in catastrophe hygiene. It characterizes the value and role of
      this science in the organization and implementation of preventive measures to
      liquidate the medicosanitary consequences of emergencies, as well as the place of
      hygienic facilities and research institutes within the framework of the Russian
      emergency service.

PMID- 16404882
TI  - [Environmental hygiene practice in the Republic of Byelarus].

PMID- 16404883
TI  - [The informative value of determination of the cytological status of nasal and
      oral mucosae in the assessment of the quality of water].
AB  - The nasal and oral mucosal cytological status was studied in children of a
      control kindergarten who used boiled Moscow tap water and in those of two
      experimental kindergartens who had drunk bottled "Troitsa" water supplemented by
      a fortified "Zolotoy Shar" drink for 6 months. Impression smears were taken from
      their nasal and oral mucosae twice: before and 6 months after water use. The data
      presented indicate that the use of the water of improved quality in its trace and
      vitamin contents may be used in preventive and rehabilitative medicine as it
      leads to improvement of the nasal and oral cytological status, by normalizing
      and/or positively affecting the latter.

PMID- 16404884
TI  - [Priority criteria for assessing the health status and prevention of diseases in
      children and adolescents].
AB  - The paper presents the currently available methods for assessing the health
      status of children and adolescents, the basic principles in the organization and
      performance of prophylactic examinations in children, including the assessment of
      their physical fitness, as well as the methods and criteria for assessing the
      phychophysiological development of adolescents, their social adaptability and
      autonomic stability. It also contains the currently used basic criteria for
      assessing the health status of children, as well as their health groups. The high
      effectiveness of children's health promotion in educational establishments can be
      achieved, by applying the basic principles in the organization and implementation
      of prophylactic and health-promoting measures.

PMID- 16404885
TI  - [The tasks and possible ways of their solution in the epidemiology of diseases
      associated with the influence of environmental factors].

PMID- 16404886
TI  - [Assessment of the trends in schoolchildren's morbidity by the results of
      prophylactic medical examinations].

PMID- 16404887
TI  - [Integral health indicators and computer systems for their assessment].

PMID- 16404888
TI  - [The specific features of the development of iodine deficiencies in children
      living under environmental pollution with fluorine compounds].
AB  - Natural iodine deficiency and ambient air pollution with fluorine compounds were
      examined for their combined influence on the prevalence and severity of iodine
      deficiency disorders. The excess intake of fluorine was shown to increase the
      incidence of thyroid diseases and to lower anthropometric indices in children.
      The preventive measures performed to eliminate iodine-deficiency disorders under
      intensive ambient air pollution with fluorine compounds were found to be
      insufficiently effective.

PMID- 16404890
TI  - [The specific features of children's adaptability to environmental factors and
      the criteria for their assessment].

PMID- 16404891
TI  - [Role of genetic studies in the evaluation of the human influence of
      environmental factors].
AB  - The authors propose to include not only a control of human populations, but also
      environmental factors (chemical, physical, and biological), and objects (to
      estimate the cumulative mutagenic activity of water, air, soil, and foodstuffs)
      in order to ensure human genetic safety. For evaluation of human cell genetic
      damage, they also propose to use the noninvasive multiple organ micronuclear
      test, by taking into account additional cardiological parameters. The results of
      this monitoring makes it possible to define higher genetic risk areas for
      warranting the necessity, priority, and nature of prophylactic measures and to
      identify a risk group of individuals to be thoroughly examined and to undergo
      health-promoting measures.

PMID- 16404889
TI  - [Children's health indices in the sociohygienic monitoring system in the area
      adjacent to a powerful radio and TV center].

PMID- 16404892
TI  - [The psychoemotional status of adolescent girls living in the urbanized areas and
      its association with their reproductive health].
AB  - The detected characteristics of the psychoemotional status of teenage girls
      living in the urbanized areas, particularly under socioeconomical ill-being can
      hamper their social adaptation, deform the type of gender behavior, and be a risk
      factor of their reproductive behavior. In this connection, there is a need for
      activating the interaction of medics and psychologists in the structure of a
      medicopedagogical stage of prophylactic medical examinations and for introducing
      stress-limiting exposures into the educational establishments.

PMID- 16404893
TI  - [Trace element status in children from Saint Petersburg].

PMID- 16404894
TI  - [Metal kinetics in the mother-fetus-neonate system upon technogenic exposure].

PMID- 16404895
TI  - [A problem in the hygienic diagnosis of health in environmental medicine].

PMID- 16404896
TI  - [Hygienic problems in the protection of the environment and human health in the
      areas of chrysotile asbestos extract and utilization].

PMID- 16404897
TI  - [A problem in health rehabilitation in the development of dysbioses under the
      influence of environmental factors].

PMID- 16404898
TI  - [Hygienic anthropopathology and preventive pediatric vertebrology].

PMID- 16404899
TI  - [Combined and multifactorial burn injuries in military conflicts: tactical
      approaches to diagnosis and treatment].
AB  - The article reflects the experience of the treatment of the servicemen with
      combined burn injuries got in the Chechen Republic (1994-1996, 1999-2001). 266
      causes of medical treatment for combined injuries where the burn was decisive
      were analyzed: 141 of which were got in the Chechen Republic in 1994-1996, 10 -
      in Daghestan in August-September of 199 and 125 - in the Chechen Republic in 1999
      2001. In the structure of sanitary losses with surgical profile the burnt
      amounted to 4,1%, and 6,4%. The development of the medical treatment system made
      it possible to reduce lethality from 13,5% to 7,5% (P < 0,05). The optimal option
      of the medical evacuation organization in local military conflicts and wars is a
      two-stage scheme of evacuation, the first stage is premedical care ann the second
      is qualified (specialized) medical care.

PMID- 16404900
TI  - [The improvement of sanatorium and health-resort services for the air force
      troops].

PMID- 16404901
TI  - [Organization of work in the radiotherapy department in Burdenko MMCH].
AB  - Radiotherapy is one of the main methods of malignant tumor treatment. The
      radiotherapy department in Burdenko Main Military-and-clinical Hospital as a part
      of a radiological center has been working for 40 years. During vhis period it has
      constantly been developing its technical base, quality of irradiation and
      professionalism of its staff. And nowadays at the modern stage there exists a
      real perspective of future development of radiological treatment for servicemen
      and their families' members basing on the radiotherapy department in Burdenko
      MMCH.

PMID- 16404902
TI  - [Surgical and combined treatment of soft tissue sarcomas of extremities].

PMID- 16404903
TI  - [Choice of treatment tactics for the recurrence of soft tissue malignant tumor].

PMID- 16404904
TI  - [The radical cystectomy with different methods of the urine derivation in urinary
      bladder carcinoma].

PMID- 16404905
TI  - [Remote results of the standard ovary cancer treatment].

PMID- 16404906
TI  - [Combined (chemo-radiation) treatment of patients with nasopharyngeal cancer].
AB  - The efficacy of parallel and successive chemoradial treatment of patients with
      nasopharynx carcinoma was investigated in the radiological center of Burdenko
      MMCH. The main group consisted of 42 patients, the control group included 44
      patients. They were from 21 to 78 years old. 71% of the patients had the 3rd and
      the 4th stages of the tumor process; 29% had the 1st and the 2nd stages; 68,6%
      had the metastatic nodal involvement of regional zones. The radial therapy of the
      locoregional zone was administered by means of the splitting course using the
      classic method of fractionating a dose up to the total optimal dose of 64-70 Gr.
      Polychemotherapy consisted of 6 courses cisplatin, farmarubicin, and platinum.
      Due to the treatment the 5-year survival rate increased from 41,2% to 78,5% (P <
      0,001). With the metastatic nodal involvement of regional zones that rate reduced
      from 83,3% to 72,8% (P > 0,05) in the main group and from 63,8% to 31,9% (P <
      0,001) in the control group.

PMID- 16404907
TI  - [The modern approach to the treatment for onychomycosis of hands and feet in the
      outpatient setting].

PMID- 16404909
TI  - [The scientific research center of military medicine, military-and-medical
      equipment and pharmacy is 75 years].

PMID- 16404908
TI  - [Effect of training for hypoxia-and-hypercapnia on the state of the external
      respiration system in the healthy subjects].

PMID- 16404910
TI  - [The half-century jubilee of the military hospital of the Baikonur cosmodrom].

PMID- 16404911
TI  - [The radiological center of the N.N. Burdenko Main Military Clinical Hospital is
      40 years].

PMID- 16404912
TI  - [The development of oncology in the N.N. Burdenko Main Military Clinical
      Hospital].

PMID- 16404913
TI  - [The department of oncology of the State Institute of Advanced Training for
      Medical Doctors of RF MD is 10 years].

PMID- 16404914
TI  - [The historical stages of oncourological support in the N.N. Burdenko Main
      Military Clinical Hospital].

PMID- 16404915
TI  - [100 years since the introduction of radon therapy].

PMID- 16404916
TI  - [A modifying action of laser irradiation of blood in radiotherapy of experimental
      tumors].

PMID- 16404917
TI  - [Naphthalan effects on phagocytic processes in peritoneal macrophages in
      secondary immunodeficiency].
AB  - Effects of naphthalan on the number of peritoneal macrophages and phagocytic
      processes were studied in vitro and in cyclophosphamide-induced immunodeficiency
      in white mice. In vitro, naphthalan increased the number of peritoneal
      macrophages and stimulated their functional processes. In conditions of secondary
      immunodeficiency the number of naphthalan applications correlated with an
      increase in quantitative and functional parameters of macrophagal immunity. Thus,
      naphthalan has an immunocorrective effects on phagocytic processes.

PMID- 16404918
TI  - [Impulse low-intensity electromagnetic field in the treatment of adolescents with
      essential arterial hypertension].
AB  - Effectiveness of different regimes of a course exposure to impulse low-intensity
      electromagnetic field (Infita unit) was studied in 69 adolescents with essential
      hypertension. A ten-day course of single 9 min procedures with 30 Hz field
      produced better antihypertensive effects than the regime used in the adults. This
      treatment provided improvement in bioelectric activity of the brain, mental
      state, central hemodynamics.

PMID- 16404919
TI  - [Low-mineral water and sapropel in the treatment of chronic cholecystitis in
      children in conditions of polluted environment].
AB  - The comparison of the course of chronic cholecystitis in children living in
      healthy and polluted regions of the Chelyabinsk Territory has demonstrated that
      industrial enronmental pollution deteriorates the course of chronic
      cholecystitis. Drinking of low-mineral water and sapropel application on hepatic
      area improved clinical parameters in the examinees.

PMID- 16404920
TI  - [Efficacy of the drinking magnesium-calcium sulfate mineral water in the combined
      treatment of duodenal ulcer comorbid with gastroesophageal reflux].
AB  - Thirty patients with duodenal ulcer in remission running in combination with
      gastroesophageal reflux disease (GERD) were divided into two groups. Patients of
      group 1 received medication (omeprasol 20 mg twice a day, motilium 10 mg 3 times
      a day) and mineral water Klyuchi (200 ml 3 times a day). Patients of group 2
      received the same medication but no mineral water. The efficacy of the treatment
      was assessed by the data obtained at esophagogastroduodenofibroscopy,
      morphological study of gastric and esophageal biopsies, 24-h pH-metry of the
      esophagus and the stomach. The results suggest that the addition of mineral water
      Klyuchi to standard medication of GERD shortens correction of clinical,
      endoscopic and morphological manifestations of the disease.

PMID- 16404921
TI  - [Infrared laser therapy in combined therapy of patients with chronic salpingo
      oophoritis].

PMID- 16404922
TI  - [Therapeutic exercise in a complex of conservative therapy of the small pelvis
      varicosity in women of the reproductive age].

PMID- 16404923
TI  - [Efficacy of marketing technologies in sanatoria].

PMID- 16404924
TI  - [Major stages of of medicopsychological rehabilitation of visually impared
      persons at a sanatorium].

PMID- 16404926
TI  - [Terminology classification for sanatorium treatment and physiotherapy].

PMID- 16404925
TI  - [Composition and quality requirements for drinking groundwater: prospecting and
      utilization].

PMID- 16404928
TI  - [Rehabilitation of the poststroke patients].

PMID- 16404927
TI  - [Balneologist V. A. Azletskii (to the his 125th birthday].

PMID- 16404929
TI  - [Physiotherapy in Raynaud disease].

PMID- 16404930
TI  - [Combined application of physical factors in patients with traumatic
      vertebrogenic neuropathy. Guide for physicians].

PMID- 16404931
TI  - [The role of heart hormones in the forming of cardiovascular pathology].

PMID- 16404932
TI  - [Tumor necrosis factor a inhibitors in treatment of Crohn's disease].

PMID- 16404933
TI  - [Risk factors and prevention of cancer of various localizations (part 1)].

PMID- 16404934
TI  - [Effect of respiratory infections on the clinical course of coronary artery
      disease].
AB  - The subjects of the study were 64 patients with coronary artery disease (CAD),
      and 38 healthy controls. The study included determination of Chlamydia pneumonia
      (CLPN), Toxoplasma gondii (TG), Herpes simplex virus (HSV) 1, 2, Epstein-Barr
      virus (EBV), and antibodies to these microorganisms. Diagnostically significant
      elevation of the serum levels of IgG antibodies to CLPN, HSV 1, 2, or TG was
      associated with CAD progression, and seropositivity to several of the agents
      strongly correlated with CAD progression. Moreover, the risk of future coronary
      events increased depending on the level of total pathogen burden. These results
      suggest that intracellular infectious agents are involved in the development of
      atherosclerosis and CAD.

PMID- 16404936
TI  - [Study of serum levels of homocystein, lipids and their peroxidation products in
      patients with coronary heart disease].
AB  - The subjects of the study were 30 patients with coronary heart disease (19--with
      stable, and 11--with instable angina), and 15 practically healthy individuals.
      The study included measurement of the levels of homocysteine (HC), total
      cholesterol, cholesterol of low-density lipoproteins, cholesterol of high-density
      lipoproteins, and lipidperoxidation (LP) products (TBA-reactive products), as
      well as coagulo-fibrinolytic parameters. The study revealed that patients with
      instable angina had significantly higher levels of HC and TBA-reactive products
      compared to those with stable angina and healthy controls. HC level correlated
      with LP processes in CHD patients (r = 0.55). Methionine loading allowed
      revealing latent hyperhomocysteinemia.

PMID- 16404935
TI  - [Thrombocyte-vascular and sero-coagulation hemostasis, and blood lipids in the
      acute period of ischemic stroke].
AB  - The subjects of the study were 46 patients at the acute stage of a first or
      repeated ischemic stroke (IS). The study revealed prevalence of procoagulating
      and thrombocyte activity of hemostasis, pronounced deficiency of physiological
      anticoagulants, high activity of Willebrand factor, and dislipidemia in these
      patients. The results show that secondary IS prophylaxy require combined
      antiaggregant therapy or combined therapy including anticoagulants and
      antithrombocyte agents plus correction of dislipidemia.

PMID- 16404937
TI  - [Oral cavity manifestations of gastroesophageal reflux disease].
AB  - The aim of the study was to investigate changes in the oral cavity and the
      gastroesophageal zone of the patients receiving rabeprazol, a proton pump
      inhibitor (PPI). The subjects were 88 patients with gastroesophageal reflux
      disease (GERD), who had changes in the oral cavity typical of this disease. The
      patients were divided into four groups. Group I included patients with non
      erosive reflux disease; the other three groups were formed according to the
      degree of the severity of reflux esophagitis in accordance with Los Angeles
      classification of GERD: A, B, and C. The patients were administered rabeprazol as
      a PPI. The study found that oral cavity changes are associated with the degree of
      the gastroesophageal reflux. The study demonstrated high efficacy of rabeprazol
      in GERD patients with oral cavity changes.

PMID- 16404938
TI  - [Polymyalgia rheumatica and giant-cell arteritis].
AB  - The subjects of the study were 112 patients with rheumatic polymyalgia (RPM) and
      giant-cell arteritis (GSA). The study shows that RPM and GSA are complicated by
      cerebral flow disturbances and myocardial infarction. Therapy with prednisolone
      and non-steroid antiinflammatory drugs reduces the risk of these complications
      and lethal outcome in patients with RPM and GSA.

PMID- 16404939
TI  - [Midocalm in complex therapy of chronic low back pain syndrome].
AB  - The aim of the study was to determine whether application of midocalm is
      appropriate in patients with chronic low back pain (LBP) from the point of view
      of quality of life (QL), efficacy and tolerance. The subjects were 50 patients
      with chronic LBP associated with spinal osteochondrosis, who underwent clinical
      examination and were questioned using four QL questionnaires: Health Assessment
      Questionnaire (HAQ), Womac osteoarthritis index Womac osteoarthritis index,
      Oswestry Low Back Pain Disability Questionnaire, and The 36-Item Short-Form
      Health Survey (SF-36). The subjects were divided into two groups. The 25 patients
      of Group I were administered nise in a dose of 100 mg twice a day during 10 days,
      the 25 patients of Group II--nise in a dose of 100 mg twice a day plus midocalm
      in a dose of 150 mg per day during the first two days and 450 mg per day from the
      third day through the tenth day. The study showed high efficacy of midocalm in
      complex therapy of patients with chronic LBP, as well as low rate of adverse
      reactions and high treatment tolerance. QL of the patients improved. Combining
      midocalm therapy with nise allows quicker positive effect in patients with
      chronic LBP and lowers need for long application of non-steroid antiinflammatory
      drugs.

PMID- 16404940
TI  - [The phospholipid spectrum of erythrocyte membranes in hemorrhagic fever with
      renal syndrome].
AB  - The subjects of the study--patients with severe hemorrhagic fever with renal
      syndrome--were divided into two groups: those who were on hemodialysis, and those
      who were not. The study included evaluation of the phospholipid spectrum of
      erythrocyte membranes in the acute period and during recovery. The results
      revealed conformational shifts in the structure of the bilipid membrane layer,
      which were maximal during the acute phase of the disease, as well as less
      prominent and varied changes in the phospholipid spectrum during recovery. This
      allows determination of the terms of rehabilitation of the patients and
      substantiates administration of membrane stabilizers as a part of complex therapy
      of residual syndrome.

PMID- 16404941
TI  - [Correlations between endogenous intoxication and excessive body weight].
AB  - The aim of the study was to analyze correlations between endogenous intoxication
      (EI) and lipid peroxidation (LP) indices in patients with cardiovascular and
      endocrine diseases and healthy individuals, taking into account the presence of
      excessive body weight (EBW), as well as to compare EI and LP indices in
      practically healthy people with and without excessive body weight (EBW). The
      subjects were 165 people, including 36 healthy individuals and 129 patients with
      cardiovascular and endocrine disease. The healthy ones were divided into two
      groups: 20 with and 16 without EBW. To evaluate the degree of EI, the
      concentration of middle-molecular-weight peptides (MMWP) was measured by the
      method offered by N. I. Gabrielyan et al. in 1984. To evaluate LP processes,
      serum levels of the secondary LP product, malonic dialdehyde, and two
      antioxidative enzymes, superoxide dismutase and catalase, were measured. The
      results show that treatment aimed at LP suppression is not appropriate; it should
      be aimed at the cause of LP activation instead, which is the increase of MMWP
      level due to EBW. LP activation significantly correlates with increase of MMWP
      blood level (p < 0.05). EBW worsens EI and activates LP in healthy people, thus
      being a stress factor to the organism. Increased MMWP level and LP activation in
      healthy individuals with EBW may be a premorbid diagnostic marker.

PMID- 16404942
TI  - [Efficacy of bemithyl and pyrazidol in patients with cerebroasthenia due to brain
      injury].
AB  - The article is dedicated to therapeutic efficacy of a combination of the
      antihypoxant bemithyl and the antidepressant pyrazidol in patients with
      asthenoneurotic and asthenovegetative syndromes after moderate isolated brain
      injury (BI). The combined therapy was shown to reduce long-term sequences of BI
      such as asthenic symptoms, stabilize both lipid peroxidation processes and serum
      antioxidative systems.

PMID- 16404943
TI  - [Indices of lipid peroxidation and atherogenic blood lipoproteins in patients
      with coronary heart disease receiving antioxidants in addition to basic therapy].
AB  - The article substantiates the necessity to administer the antioxidants--vitamins
      E and ascorbic acid--to patients suffering from coronary heart disease with type
      II hyperlipoproteinemia in addition to basic therapy, and demonstrates their
      efficacy and safety. The authors discuss the mechanism of the positive effect of
      these antioxidants on lipid peroxidation and the blood content of atherogenic
      lipoproteins.

PMID- 16404944
TI  - [New approaches to gastric ph-metry].
AB  - The article is dedicated to three methods of gastric ph-metry: individualized ph
      metry of two gastric zones, endoscopic ph-metry, and microprobe and reference
      electrode ph-metry.

PMID- 16404945
TI  - [Potentialities of alternative non-drug therapy of gastric ulcer].
AB  - The aim of the study was to evaluate the influence of non-invasive laser therapy
      on the efficacy of gastric ulcer therapy. The study revealed shortening of the
      time to ulcer cicatrization in patients who were treated with laser emission of
      the organospecific iridic zones and immunocompetent body parts in addition to
      standard drug therapy.

PMID- 16404946
TI  - [Idiopathic occluding mitral thrombosis].

PMID- 16404947
TI  - [Skin melanoma in a physician's practice].

PMID- 16404948
TI  - A high throughput targeted gene disruption method for Alternaria brassicicola
      functional genomics using linear minimal element (LME) constructs.
AB  - Alternaria brassicicola causes black spot disease of cultivated Brassicas and has
      been used consistently as a necrotrophic fungal pathogen for studies with
      Arabidopsis. In A. brassicicola, mutant generation has been the most rate
      limiting step for the functional analysis of individual genes due to low
      efficiency of both transformation and targeted integration. To improve the
      targeted gene disruption efficiency as well as to expedite gene disruption
      construct production, we used a short linear construct with minimal elements, an
      antibiotic resistance selectable marker gene, and a 250- to 600-bp-long partial
      target gene. The linear minimal element (LME) constructs consistently produced
      stable transformants for diverse categories of genes. Typically, 100% of the
      transformants were targeted gene disruption mutants when using the LME
      constructs, compared with inconsistent transformation and usually less than 10%
      targeted gene disruption with circular plasmid disruption constructs. Each mutant
      displayed a unique molecular signature thought to originate from endogenous
      exonuclease activities in fungal cells. Our data suggests that a DNA double
      stranded break repair mechanism (DSBR) functions to increase targeting
      efficiency. This method is advantageous for high throughput gene disruption,
      overexpression, and reporter gene introduction within target genes, especially
      for asexual filamentous fungi where genetic approaches are unfavorable.

PMID- 16404949
TI  - DspA/E, a type III effector essential for Erwinia amylovora pathogenicity and
      growth in planta, induces cell death in host apple and nonhost tobacco plants.
AB  - Erwinia amylovora is responsible for fire blight, a necrotic disease of apples
      and pears. E. amylovora relies on a type III secretion system (TTSS) to induce
      disease on hosts and hypersensitive response (HR) on nonhost plants. The DspA/E
      protein is essential for E. amylovora pathogenicity and is secreted via the TTSS
      in vitro. DspA/E belongs to a type III effector family that is conserved in
      several phytopathogenic bacteria. In E. amylovora, DspA/E has been implicated in
      the generation of an oxidative stress during disease and the suppression of
      callose deposition. We investigated the fate of DspA/E in planta. DspA/E
      delivered artificially to apple or tobacco cells by agroinfection induced
      necrotic symptoms, indicating that DspA/E was probably injected via the TTSS. We
      confirmed that DspA/E acts as a major cell-death inducer during disease and HR,
      because the dspA/E mutant is severely impaired in its ability to induce
      electrolyte leakage in apple and tobacco leaves. Expression of the defense marker
      gene PR1 was delayed when dspA/E was transiently expressed in tobacco, suggesting
      that DspA/E-mediated necrosis may be associated with an alteration of defense
      responses.

PMID- 16404950
TI  - The endo-beta-1,4-xylanase xyn11A is required for virulence in Botrytis cinerea.
AB  - Phytopathogenic fungi can degrade xylan, an abundant hemicellulose in plant cell
      walls, by the coordinate action of a group of extracellular enzymes. Among these,
      endo-beta-1,4-xylanases carry out the initial breakdown by cleaving internal
      bonds in the polymer backbone. We have isolated and characterized a gene, xyn11A,
      coding for an endo-beta-1,4-xylanase belonging to family 11 of glycosyl
      hydrolases. xyn11A was shown to be induced by xylan and repressed by glucose and
      to be expressed in planta. The disruption of xyn11A caused only a moderate
      decrease, about 30%, in the level of extracellular endo-beta-1-4-xylanase
      activity and in the growth rate, with beechwood xylan as the only carbon source.
      However, deletion of the gene had a more pronounced effect on virulence, delaying
      the appearance of secondary lesions and reducing the average lesion size by more
      than 70%. Reintroducing the wild-type gene into the mutant strains reversed this
      phenotype back to wild type.

PMID- 16404951
TI  - Ethylene sensing and gene activation in Botrytis cinerea: a missing link in
      ethylene regulation of fungus-plant interactions?
AB  - Ethylene production by infected plants is an early resistance response leading to
      activation of plant defense pathways. However, plant pathogens also are capable
      of producing ethylene, and ethylene might have an effect not only on the plant
      but on the pathogen as well. Therefore, ethylene may play a dual role in fungus
      plant interactions by affecting the plant as well as the pathogen. To address
      this question, we studied the effects of ethylene on the gray mold fungus
      Botrytis cinerea and the disease it causes on Nicotiana benthamiana plants.
      Exposure of B. cinerea to ethylene inhibited mycelium growth in vitro and caused
      transcriptional changes in a large number of fungal genes. A screen of fungal
      signaling mutants revealed a Galpha null mutant (deltabcg1) which was ethylene
      insensitive, overproduced ethylene in vitro, and showed considerable
      transcriptional changes in response to ethylene compared with the wild type.
      Aminoethoxyvinylglycine (AVG)-treated, ethylene-nonproducing N. benthamiana
      plants developed much larger necroses than ethylene-producing plants, whereas
      addition of ethylene to AVG-treated leaves restricted disease spreading. Ethylene
      also affected fungal gene expression in planta. Expression of a putative
      pathogenicity fungal gene, bcspl1, was enhanced 24 h after inoculation in
      ethylene-producing plants but only 48 h after inoculation in ethylene
      nonproducing plants. Our results show that the responses of B. cinerea to
      ethylene are partly mediated by a G protein signaling pathway, and that ethylene
      induced plant resistance might involve effects of plant ethylene on both the
      plant and the fungus.

PMID- 16404952
TI  - Sinorhizobium fredii HH103 mutants affected in capsular polysaccharide (KPS) are
      impaired for nodulation with soybean and Cajanus cajan.
AB  - The Sinorhizobium fredii HH103 rkp-1 region, which is involved in capsular
      polysaccharides (KPS) production, was isolated and sequenced. The organization of
      the S. fredii genes identified, rkpUAGHIJ and kpsF3, was identical to that
      described for S. meliloti 1021 but different from that of S. meliloti AK631. The
      long rkpA gene (7.5 kb) of S. fredii HH103 and S. meliloti 1021 appears as a
      fusion of six clustered AK631 genes, rkpABCDEF. S. fredii HH103-Rif(r) mutants
      affected in rkpH or rkpG were constructed. An exoA mutant unable to produce
      exopolysaccharide (EPS) and a double mutant exoA rkpH also were obtained. Glycine
      max (soybean) and Cajanus cajan (pigeon pea) plants inoculated with the rkpH,
      rkpG, and rkpH exoA derivatives of S. fredii HH103 showed reduced nodulation and
      severe symptoms of nitrogen starvation. The symbiotic capacity of the exoA mutant
      was not significantly altered. All these results indicate that KPS, but not EPS,
      is of crucial importance for the symbiotic capacity of S. fredii HH103-Rif(r). S.
      meliloti strains that produce only EPS or KPS are still effective with alfalfa.
      In S. fredii HH103, however, EPS and KPS are not equivalent, because mutants in
      rkp genes are symbiotically impaired regardless of whether or not EPS is
      produced.

PMID- 16404953
TI  - Apple proteins that interact with DspA/E, a pathogenicity effector of Erwinia
      amylovora, the fire blight pathogen.
AB  - The disease-specific (dsp) gene dspA/E of Erwinia amylovora encodes an essential
      pathogenicity effector of 198 kDa, which is critical to the development of the
      devastating plant disease fire blight. A yeast two-hybrid assay and in vitro
      protein pull-down assay demonstrated that DspA/E interacts physically and
      specifically with four similar putative leucine-rich repeat (LRR) receptor-like
      serine/threonine kinases (RLK) from apple, an important host of E. amylovora. The
      genes encoding these four DspA/E-interacting proteins of Malus xdomestica (DIPM1
      to 4) are conserved in all genera of hosts of E. amylovora tested. They also are
      conserved in all cultivars of apple tested that range in susceptibility to fire
      blight from highly susceptible to highly resistant. The four DIPMs have been
      characterized, and they are expressed constitutively in host plants. In silico
      analysis indicated that the DIPMs have similar sequence structure and resemble
      LRR RLKs from other organisms. Evidence is presented for direct physical
      interaction between DspA/E and the apple proteins encoded by the four identified
      clones, which may act as susceptibility factors and be essential to disease
      development. Knowledge of DIPMs and the interaction with DspA/E thus may
      facilitate understanding of fire blight development and lead to new approaches to
      control of disease.

PMID- 16404954
TI  - Tomato flower abnormalities induced by stolbur phytoplasma infection are
      associated with changes of expression of floral development genes.
AB  - Tomato (Lycopersicon esculentum cv. Micro-Tom) plants infected by the stolbur
      phytoplasma (isolate PO) display floral abnormalities, including sepal
      hypertrophy, virescence, phyllody, and aborted reproductive organs, which are
      reminiscent of those observed in Arabidopsis thaliana mutants affected in flower
      development genes. Semiquantitative reverse transcription-polymerase chain
      reaction and in situ RNA hybridization were used to compare expressions of
      meristem and flower development genes in healthy and stolbur phytoplasma-infected
      tomatoes. In infected plants, FALSIFLORA (FA), controlling the identity of the
      inflorescence meristem, was up-regulated, whereas LeWUSCHEL (LeWUS) and
      LeCLAVATA1 (LeCLV1), regulating the meristem development, and LeDEFICIENS
      (LeDEF), responsible for the organ (petals and stamens) identity within the
      flower, were down-regulated regardless of the development stage of the flower
      bud. In contrast, expression of TAG1, which regulates stamen and carpel
      identities and negatively controls LeWUS, was up-regulated at the early stages
      and down-regulated at the late stages. In situ RNA hybridization analyses
      revealed that TAG1 transcripts were restricted to the same floral meristem
      territories in healthy and infected tomatoes, indicating that tissue-specific
      expression of TAG1 was not affected by the stolbur phytoplasma infection. Taken
      together, these data indicate that flower malformations of stolbur phytoplasma
      infected tomatoes are associated with early changes in the expression of key
      flower development genes. The possible mechanisms by which the multiplication of
      stolbur phytoplasma in tomato sieve tubes deregulates floral development are
      discussed.

PMID- 16404955
TI  - Identification of open reading frames unique to a select agent: Ralstonia
      solanacearum race 3 biovar 2.
AB  - An 8x draft genome was obtained and annotated for Ralstonia solanacearum race 3
      biovar 2 (R3B2) strain UW551, a United States Department of Agriculture Select
      Agent isolated from geranium. The draft UW551 genome consisted of 80,169 reads
      resulting in 582 contigs containing 5,925,491 base pairs, with an average 64.5%
      GC content. Annotation revealed a predicted 4,454 protein coding open reading
      frames (ORFs), 43 tRNAs, and 5 rRNAs; 2,793 (or 62%) of the ORFs had a functional
      assignment. The UW551 genome was compared with the published genome of R.
      solanacearum race 1 biovar 3 tropical tomato strain GMI1000. The two
      phylogenetically distinct strains were at least 71% syntenic in gene
      organization. Most genes encoding known pathogenicity determinants, including
      predicted type III secreted effectors, appeared to be common to both strains. A
      total of 402 unique UW551 ORFs were identified, none of which had a best hit or
      >45% amino acid sequence identity with any R. solanacearum predicted protein; 16
      had strong (E < 10(-13)) best hits to ORFs found in other bacterial plant
      pathogens. Many of the 402 unique genes were clustered, including 5 found in the
      hrp region and 38 contiguous, potential prophage genes. Conservation of some
      UW551 unique genes among R3B2 strains was examined by polymerase chain reaction
      among a group of 58 strains from different races and biovars, resulting in the
      identification of genes that may be potentially useful for diagnostic detection
      and identification of R3B2 strains. One 22-kb region that appears to be present
      in GMI1000 as a result of horizontal gene transfer is absent from UW551 and
      encodes enzymes that likely are essential for utilization of the three sugar
      alcohols that distinguish biovars 3 and 4 from biovars 1 and 2.

PMID- 16404957
TI  - [Microsurgical angioarchitectonics of depth structures of the brain and depth
      interarterial anastomoses].
AB  - The paper deals with the investigation studying the localization of a structure
      and showing the ways of formation of depth interarterial anastomoses of the
      brain. Three areas of deep interarterial anastomoses are identified, which are
      characterized by their symmetric pattern and formed by the arteries supplying
      blood to the deep cerebral structures and which create an epithalamic circle of
      anastomoses similar to the basal hypothalamic arterial circle of Willis. The
      existence of depth interarterial anastomoses points to the sole functional
      significance of depth structures of the brain. Depth epithalamic anastomoses are
      mechanisms that are responsible for the additional redistribution of blood from
      different vascular beds when cerebral blood flow is impaired in the depth
      structures and their presence should be taken into account during neurosurgical
      interventions.

PMID- 16404956
TI  - Genetics of symbiosis in Lotus japonicus: recombinant inbred lines, comparative
      genetic maps, and map position of 35 symbiotic loci.
AB  - Development of molecular tools for the analysis of the plant genetic contribution
      to rhizobial and mycorrhizal symbiosis has provided major advances in our
      understanding of plant-microbe interactions, and several key symbiotic genes have
      been identified and characterized. In order to increase the efficiency of genetic
      analysis in the model legume Lotus japonicus, we present here a selection of
      improved genetic tools. The two genetic linkage maps previously developed from an
      interspecific cross between L. japonicus Gifu and L. filicaulis, and an
      intraspecific cross between the two ecotypes L. japonicus Gifu and L. japonicus
      MG-20, were aligned through a set of anchor markers. Regions of linkage groups,
      where genetic resolution is obtained preferentially using one or the other
      parental combination, are highlighted. Additional genetic resolution and
      stabilized mapping populations were obtained in recombinant inbred lines derived
      by a single seed descent from the two populations. For faster mapping of new
      loci, a selection of reliable markers spread over the chromosome arms provides a
      common framework for more efficient identification of new alleles and new
      symbiotic loci among uncharacterized mutant lines. Combining resources from the
      Lotus community, map positions of a large collection of symbiotic loci are
      provided together with alleles and closely linked molecular markers. Altogether,
      this establishes a common genetic resource for Lotus spp. A web-based version
      will enable this resource to be curated and updated regularly.

PMID- 16404958
TI  - [Familial intracranial aneurysms].
AB  - The study included 38 patients with intracranial aneurysms, whose close relatives
      had experienced intracranial hemorrhages. The patients' relatives were divided
      into 2 groups according to the verification of the source of hemorrhage. The
      individuals at risk for aneurysmal disease in whom aneurysms should be sought
      before their rupture were examined. The patients with familial aneurysms were
      found to tend to rupture at younger age than those without familial aneurysms
      (the so-called sporadic aneurysms). The high rates of mortality due to
      intracranial bleeding were observed among the relatives of patients from the
      study group. Screening study of the first-order relatives of the patients with
      prior aneurysmal subarachnoidal hemorrhage is the method of choice in detecting
      unruptured cerebrovascular aneurysms. Early detection and switching-off of
      asymptomatic aneurysms may reduce mortality and disability rates in this group of
      patients.

PMID- 16404959
TI  - [Chronic spinal cord electrostimulation in the management of neurogenic pain].
AB  - According to the data of epidemiological surveys made in Russia, the prevalence
      of chronic pain (without cancer diseases being kept in mind) accounts for less
      than 40% of the adult population and these figures tend to grow steadily. Despite
      a continuous increase in the potentialities of pharmacotherapy, physiotherapy,
      and psychotherapy, the efficiency of treatment in patients suffering from various
      pains has remained ineffective so far. Surgical treatments for pain include
      anatomic, destructive (neuroablation), and non-destructive (electrical
      stimulation and neuromodulation) operations. The purpose of the paper is to
      present the results of use of chronic spinal cord stimulation in 10 patients (6
      males and 4 females) with severe drug-resistant pain. The patients' age was 32 to
      74 years (mean 47.2 years). The duration of the pain syndrome before surgery
      averaged 6 years (3-13 years). The severity of pain and its influence on the
      quality of life were assessed, by using a modified 10-score visual analogue
      scale. The operation was performed in 2 steps. The step involved electrode
      implantation along the Tuochi needle under X-ray control. If there were positive
      postoperative results, the second stage was implantation of the subcutaneous part
      of the system for chronic stimulation. Positive (excellent and good) results were
      obtained in 9 of the patients, excellent results being in 5 patients. The follow
      up averaged 18 months (6 to 28 months). The late postoperative positive result
      remained in 8 patients. Two patients were observed to have complications as
      displacement of an epidural electrode, which required surgical correction of its
      position. Resurgery restored the antipain effect of stimulation. Chronic epidural
      stimulation can be the method of choice in treating neurogenic pain since it is
      minimally invasive and more effective than other surgical treatments.

PMID- 16404960
TI  - [Analysis of the results of endoscopic surgical treatment for hernias of the
      lumbosacral disks].
AB  - The paper provides a comparative analysis of the results of treatment in the
      patients with disk hernia at the lumbosacral levels, who have been endoscopically
      operated on by a modified procedure described by J. Destandau and by the routine
      procedure. In the study group, 58 patients (31 males and 27 females) were
      operated on. The results of treatment were assessed, by using the MacNab spinal
      endoscopic intervention scale: there were good results in 88% of cases, fair
      results in 8.6%, and poor ones in 3.4% (2 patients). In the control group, these
      were 77.4, 17.8, and 4.8%, respectively. The procedure proposed by the authors
      for fenestration of the intervertebral disk may extend indications for endoscopic
      diskectomy and its capacities in ossified disk hernias. Two-stage traction of the
      root may minimize its injury, particularly in herniated median and paramedian
      disks.

PMID- 16404961
TI  - [The specific features of surgery of herniated intervertebral disks].
AB  - In 200 patients with posterolateral and foraminal hernias, the sizes of
      intervertebral foramens were studied by anatomic methods and on the operating
      table. There was evidence for the effectiveness of controlled decompression of
      neurovascular formations with the optimum foremen-root ratio of 1.5-1.8:8.1.
      Outcomes of different procedures of the operation were comparatively analyzed.
      Controlled decompression exhibited its advantage in reducing poor outcomes to
      1.6%.

PMID- 16404962
TI  - [Ethical problems of modern neurosurgery].

PMID- 16404963
TI  - [Giant cavernous malformation of the cerebellum in a baby].
AB  - The paper presents a rare case of successful removal of giant cavernous
      malformation of the cerebellum in a baby. It describes the specific features of
      differential diagnosis of space-occupying lesions of the posterior cranial fossa
      in infants in detail.

PMID- 16404964
TI  - [Dorsal extradural arachnoid cyst at the Th(VII)-Th(X) level, causing chronic
      progressive myelopathy].
AB  - The paper describes a rare case of an extradural spinal arachnoid cyst in a 15
      year-old boy, illustrates surgical treatment policy in detail, and reviews the
      current literature on this pathology.

PMID- 16404965
TI  - [Chronic neurogenic pelvic pain syndrome].

PMID- 16404966
TI  - [Neurosurgical service of the Russian Federation (on the occasion of the 80th
      anniversary of foundation of the Prof. A. L. Polenov Research Neurosurgery
      Institute)].

PMID- 16404967
TI  - [Biochemical markers of bone metabolism and bone tissue losses after
      allotransplantation of the cadaveric kidney: a cross-sectional].
AB  - The biochemical markers of bone metabolism (osteocalcin (OC), C- and N-terminal
      procollagen I propeptides (PICP) and PINP), bone alkaline phosphatase (BALP),
      deoxypyridinoline (DPD), beta-crosslaps (beta-CL), bone acid phosphatase (BAP),
      osteoprotegerin (OPG), insulin-like growth factor I (IGF-I), and parathyroid
      hormone (PTH)), daily urinary calcium excretion (DUCE) (intestinal calcium
      absorption), and lumbar and hip bone mineral density (BMD) were determined in 195
      patients (78 females and 74 males with normal function of the grafted kidney and
      11 females and 31 males with chronic renal failure (CRF) 40 +/- 33 months after
      renal transplantation (RT). All RT recipients received triple immunosuppressive
      therapy (cyclosporin, prednisolone, and azathioprine). All groups showed a
      significant increase in resorption markers and a moderate increase in bone
      formation markers (except BALP), which suggested bone remodeling dissociation, as
      well as elevated levels of PTH and OPG and decreased DUCE and BMD in the
      vertebral column and hip. Increased bone metabolism and decreased intestinal
      calcium absorption were largely pronounced in CRF. In the majority of recipients,
      the BMD reduction in the vertebral column and hip was moderate (osteopenia) and
      only in male recipients with CRF, axial osteopenia was concurrent with peripheral
      osteoporosis. The main predictor of accelerated bone metabolism and BMD losses
      following RT was hyperparathyroidism mainly caused by decreased renal graft
      function. Decreased IGF-I may be a cause of bone remodeling dissociation after
      RT/ and the increase in OPG seems to be compensatory, which suppresses bone
      resorption and reduces bone losses.

PMID- 16404969
TI  - [Serological diagnosis of Helicobacter infection: comparison of the analytical
      capacities of three test systems for enzyme immunoassay].

PMID- 16404968
TI  - [Preparation of monoclonal antibodies to the Fc-fragment of human IgG and the use
      of their based immunoenzyme conjugates].
AB  - An original kit containing 17 clones of hybridomas, the producers of monoclonal
      antibodies (MCAb) against the Fc-fragments of human IgG, has been obtained. The
      possibility of using horseradish peroxidase conjugates of obtained MCAb as a part
      of ELISA test systems (Diaproph-Med, Ukraine) was comparatively studied. The
      application of peroxidase conjugates of two monoclonal antibodies (156C10 and
      153H11) as part of five diagnostic kits was shown to provide a high specificity
      and a high sensitivity.

PMID- 16404970
TI  - [Nonpalpable breast masses: outpatient diagnostic methods].

PMID- 16404971
TI  - [History and the present day. The 80th anniversary of the Department of Clincal
      Laboratory Diagnosis, Russian Moscow Academy of Postgraduate Training].

PMID- 16404972
TI  - [Modern progress in the molecular cytogenetic diagnosis of hereditary diseases (a
      lecture)].

PMID- 16404973
TI  - [Diagnosis of numerical chromosomal aberrations in the cells of spontaneous
      abortions by multicolor fluorescence in situ hybridization (MFISH)].
AB  - According to different estimates, as high as 15-20% of all the pregnancies result
      in spontaneous abortions (SA) at different gestational periods. Identification of
      abnormalities leading to SA is of great importance for practical medicine, mainly
      for medical genetic counseling of married couples with impaired reproductive
      function. The diagnosis of chromosomal aberrations on the basis of SA materials
      is known to have a number of methodological difficulties. The present paper deals
      with the identification of numerical anomalies in the SA material by multicolor
      fluorescence in situ hybridization (MFISH). This technique using an original
      collection of DNA probes for chromosomes 1, 9, 13/21, 14/22, 15, 16, 18, X, and Y
      was applied to the study of chromosomal aberrations in 224 spontaneous abortion
      specimens. Numerical chromosomal aberrations were found in 122 (54.5%) cases. The
      cells of all the studied specimens exhibited aneuploidy of chromosome X in 17%
      cases; chromosome 16 in 12%, chromosomes 13/21 in 5.8%, chromosomes 14/22 in
      4.9%, chromosomes 9 and 18 in 1.3% (each), chromosome 15 in 0.9%, chromosome 1 in
      0.45%. Polyploidy was detected in 13.3% of cases; concomitant abnormalities were
      found in 7 cases. Analysis of the findings has led to the conclusion that MFISH
      can be successfully used in the diagnosis of numerical chromosomal aberrations of
      CA cells.

PMID- 16404975
TI  - [The ISO international standard 17511-2003].

PMID- 16404974
TI  - [Quantitative analysis of fluorescence in situ hybridization (FISH) signals for
      molecular cytogenetic diagnosis].
AB  - Molecular cytogenetic diagnosis of chromosomal aberrations, by using fluorescence
      in situ hybridization (FISH) requires the introduction of quantitative approaches
      to estimating hybridization signals. Specifically, this estimation is required
      for the differentiation of monosomy and for the superposition of the signals in
      the diagnosis of mosaic forms of chromosomal syndromes, as well for the
      determination of the parental origin of homologous chromosomes. The present paper
      proposes an approach to rapidly estimating FISH signals, based on image capture
      by a CCD digital chamber and a fluorescence microscope, and to measuring the
      intensity of hybridization signals. This approach has been shown to be highly
      effective in differentiating the parent origin of chromosomes, by applying
      original chromosome-specific DNA tests. It has been successfully used in the
      study of numerical chromosomal aberrations in various biological materials. By
      taking into account the findings and as well as earlier described quantitative
      FISH analyses applied to basic studies, the authors discuss whether the
      quantitative FISH analyses can be used for the molecular cytogenetic diagnosis of
      hereditary diseases.

PMID- 16404976
TI  - [Formation of probioticotherapy in Russia].
AB  - Probioticotherapy and probioticoprophylaxis have been applied widely in Russia
      and the world of late. The article presents the main medical, strain-related, and
      biotechnological stages of their development in this country, in comparison with
      the results of the world practice. The authors substantiate appropriateness of
      creation of probiotics and which would contain either only growth medium
      components, able to activate normoflora (to increase colonization ability and
      stimulate production of biologically active substances) upon entering the
      organism, or only probiotic strain components and/or biologically active
      substances produced by biologically active strains in mono- or associative
      cultivation, or combination of the listed components.

PMID- 16404977
TI  - [Medical microbial ecology: some of the overall results and research prospects].
AB  - The review discusses data of fundamental and applied research in human microbial
      ecology. Having analyzed these data, the author concludes that in the natural
      habitats these is practically no biochemical process or function of a living
      organism that would not need a direct or indirect participation of symbiotic
      organisms. The condition of these organisms should be considered one of the main
      biogenic factors that determine human health and pathology. The author offers a
      range of measures that would allow development and introduction of fundamentally
      new approaches to prevention and treatment of the most wide-spread diseases, as
      well as application of microorganisms of normal intestinal microflora of man in
      industrial biotechnology.

PMID- 16404978
TI  - [Optimization of treatment of children with acute intestinal infections by
      application of Russian biological microbial preparations].
AB  - The article presents the results of long-term (several years) use of Russian
      bifido- and lactocontaing probiotics and data on the clinicolaboratory
      effectiveness of bifidumbacterin forte, probifor, bifidin, bifilis, calcidum,
      florin forte, acipol and acilact in children with various intestinal infections
      of known and unknown etiology. The presented results were obtained by studies
      conducted according to the requirements of The Governmental Program of L. A.
      Tarasevich State Institute of Standartization and Medical Biological Preparation
      Control, which included randomization of groups of patients receiving codified
      preparations or placebo according to their age, nosology, the degree of the
      process severity, premorbid status, and the time when the treatment was started.
      Each of the programs included several hundreds of children, receiving probiotics;
      in which of the programs the studies were multicentered. The courses of treatment
      with probiotics were short (1 to 2 weeks). No significant adverse effects were
      observed.

PMID- 16404979
TI  - [Dysbiotic conditions and their management].
AB  - The authors present data concerning the role of normal intestinal microflora as a
      non-specific resistance factor. They systematize the notion of intestinal
      dysbacteriosis as a clinicolaboratory syndrome, observed in patients with various
      gastrointestinal pathology, adduce the characteristics of the preparations of
      probiotics, prebiotics, and synbiotics, and discuss the mechanisms of their
      action, as well as their efficacy in the management and prevention of
      microecological disturbances of the intestinal tract. It is recommended that
      probiotic preparations are administered according to the principle of
      microecological adequacy, taking into account the condition of the microflora, as
      well as the phase, stage, and character of the underlying disease. Some
      preparations should be used for preventive, others--for therapeutic purposes. The
      authors stress that antibioticotherapy is indicated only in cases of clinically
      severe infectious process; such therapy should be followed by reestablishment of
      the normal microflora with proper probiotic preparations.

PMID- 16404980
TI  - [Experience of pediatric application of bifidumbacterin multi, a biologically
      active food supplement].
AB  - The article is dedicated to a clinical trial of Bifidumbacterin Multi-1, a
      biologically active food supplement (BAFS) for children aged 0 to 3 years. The
      study showed that application of BAFS in children with intestinal dysbiosis
      helped to cope with the symptoms of alimentary disturbances, promoted improvement
      of body mass index, increase of hemoglobin end erythrocyte level, suppression of
      zymotic and putrefactive dyspepsia, decrease of inflammation of the intestinal
      mucosa, elimination of bibidobacterial deficit, and reduction of conditionally
      pathogenic microflora. Bifidumbacterin Multi-1 was well tolerated and highly
      effective according to clinical and laboratory data. This preparation may be
      recommended as a component of complex therapy in children aged 0 to 3 years old.

PMID- 16404981
TI  - [Acilact and improvement of the health status of sickly children].
AB  - A complex study of the effects of Acilact on the immune and interferon status,
      phagocyte defense, and cytokine balance in sickly children showed that Acilact
      had a positive effect on the immune system in these patients. The preparation is
      able to normalize abnormal immune parameters, and does not influence healthy
      immune system. In some ways Acilact has advantages over IRS 19 vaccine.
      Simultaneous administration of these two preparations is appropriate in some
      cases.

PMID- 16404982
TI  - [Pre-clinical trials of new spore probiotics].
AB  - The paper presents the results of a pre-clinical trial of Bacillus bacterial
      strains that are ingredients of biosporin, bisporin, and irilis, new Russian
      probiotic preparations. The study included determination of the cultural and
      biochemical properties of the probiotic strains, their antagonistic activity,
      adhesion ability, resistance to various biological liquids, and the length of
      their persistence in mouse alimentary tract. The listed properties were compared
      with those of foreign commercial preparations, bactisubtil and enterogermin. The
      study demonstrated high antagonistic activity of biosporin, bisporin, and irilis
      against many bacteria of different taxonomic groups, and Candidae. Besides this,
      the study showed that, unlike similar foreign preparations, the Russian ones were
      characterized by relatively low adhesive ability, short-term persistence, and
      absence of virulence factors. According to the results of the study, the most
      prospective probiotic strains for further clinical application are B. subtilis
      VKPM B-8611 and B. licheniformis VKPM B-8610, an irilis ingredient.

PMID- 16404984
TI  - [Significance of rehabilitation and prophylaxis in modern medicine].

PMID- 16404983
TI  - [The effects of the microbial components of the probiotic Acilact on the cell
      mediated immunity factors under experimental conditions].
AB  - The authors analyzed the effects of the microbial components of the probiotic
      Acilact on the cell-mediated factors of the immune homeostasis. According to the
      results, L. acidophilis stimulates the functional activity of immunocompetent
      cells, especially T-cell mediated immunity with strain- and dose-depending
      differences in intensity. The study demonstrated the ability of L. acidophilis to
      activate expression of the genes of pro-inflammatory cytokines (IFNgamma, IL-6,
      12, and TNFalpha), to induce production of IFNalpha and IFNgamma, and increase
      interferon production, with additional stimulation of lymphoid organ cells with
      specific inductors in vitro. The study established that L. acidophilis stimulates
      production of macrophage migration inhibition factor by immunocompetent cells of
      Peyer's plaques and the splen, and induces its quantitative increase in the serum
      of CBA mice. The study detected immunocorrecting effect of L. acidophilis by the
      example of experimental shigellous infection, demonstrated intensification of the
      prolipherative activity of immunocompetent T-cells, induction of the expression
      of the genes of pro-inflammatory cytokines (IFNgamma, IL-1beta, 6, 12, and
      TNFalpha), but not IL4 and 10, increase of synthesis of IFNalpha and IFNgamma by
      the cells of Peyer's plaques, the splen and thymus. The obtained results prove
      the immunological effect of the probiotic preparation Acilact, based on the
      strains L. acidophilis NK1 and L. acidophilis K3(111)24.

PMID- 16404985
TI  - Blackhead disease (histomoniasis) in poultry: a critical review.
AB  - After its discovery in 1893 in Rhode Island, blackhead disease was reported
      across the continent and soon in many other countries. It decimated the turkey
      industry in New England and followed production like a faithful shadow. Blackhead
      disease causes high mortality in turkeys, sometimes approaching 100% of a flock.
      In chickens, the mortality may be 10%-20% with high morbidity, although many
      outbreaks pass unnoticed. Early workers identified Histomonas meleagridis, a
      protozoan related to Entamoeba histolytica, Giardia lamblia, and Trichomonas, as
      the causative agent. Like many other parasites, its life cycle is complex,
      involving as an intermediate host, the common cecal worm Heterakis gallinarum.
      The necessity for bacteria for Histomonas to become virulent in the turkey and
      chicken, notably Escherichia coli, Bacillus subtilis, and Clostridium spp., was
      discovered by research in gnotobiotic birds. Changes in management brought the
      disease under control, although it remained the first cause of mortality in
      turkeys until modern antihistomonal products were developed after WWII. The ban
      of nitroimidazole products in the United States and Europe was followed by an
      upsurge in reported cases in turkeys and chickens. Immunization is not an option
      for prevention, as birds do not reliably become resistant to reinfection after
      suffering a primary exposure. Recent research demonstrated that histomoniasis
      could spread rapidly through a flock of turkeys by direct contact, probably
      involving the phenomenon of cloacal drinking. Direct transmission was not
      demonstrated for chickens, stressing dependence on H. gallinarum as the source of
      infection. The lack of suitable treatment drugs or vaccines emphasizes the
      importance of prevention by worm control and management.

PMID- 16404986
TI  - Commercial immunoassay kits for the detection of influenza virus type A:
      evaluation of their use with poultry.
AB  - Five antigen capture immunoassay test kits, Directigen Flu A (Becton Dickinson),
      QuickVue Influenza test kit (Quidel), FLU OIA (ThermoBiostar), Zstat Flu (ZymeTx,
      Inc.) and NOW FLU A Test (Binax) were used to detect avian influenza virus (AIV)
      in clinical specimens as per manufacturers' protocols. Each kit was shown to be
      specific for AIV propagated in embryonating chicken eggs (ECE); other respiratory
      viruses of poultry tested gave negative results. The Directigen Flu A kit proved
      to be 10-fold more sensitive than the other kits, capable of detecting 10(4.7)
      mean embryo lethal dose (ELD50)/ml in allantoic fluid; this is more sensitive
      than the hemagglutination test using chicken erythrocytes. None of the kits
      proved to be sufficiently sensitive to reliably detect AIV in oropharyngeal and
      cloacal swabs collected from chickens experimentally infected with AIV subtype
      H6N2. In two different experiments, individual swabs and pools of five or six
      swabs were tested. By virus isolation, 39 individual oropharyngeal swabs tested
      positive for AIV, but Directigen and Flu OIA only detected 2/39 and NOW FLU A
      1/39. Zstat and QuickVue did not detect any. Five individual cloacal swabs
      positive by virus isolation were negative with all five kits. In a second
      experiment using pools of five swabs, 26 swab pools were positive by virus
      isolation and 5/26 were positive by Directigen, the only kit to provide any
      positive results. Five cloacal swab pools were also positive by virus isolation
      and 1/5 was positive by Directigen; all other test kits were negative. All of
      these experiments were performed using the H6N2 subtype of AIV. The results are
      disappointing, as the kits have proven to be insensitive for detecting AIV when
      compared with the gold standard, virus isolation. This limits their use in
      diagnostic field investigations. Individual or groups of chickens could be
      assumed to be positive for AIV if positive by any of the kits, but a negative
      result with any of the kits would not prove that birds were AIV free.

PMID- 16404987
TI  - Oral infection with chicken anemia virus in 4-wk broiler breeders: lack of effect
      of major histocompatibility B complex genotype.
AB  - The pathologic consequences of chicken anemia virus (CAV) oral inoculation in 4
      wk-old broiler breeders of different major histocompatibility B complex (MHC)
      genotypes were evaluated. MHC B complex was determined by hemagglutination and
      sequence-based typing. Clinical signs, serology, gross lesions, histopathologic
      analysis, and CAV genome quantification were used to evaluate disease
      progression. Clinical disease was not apparent in the inoculated broilers
      throughout the experimental period. At 14 days postinoculation, antibodies
      against CAV were detected in 26.4% (29/110) of the inoculated birds. The
      distribution of percent positive was 34.6% (9/26) and 32.3% (10/31) of the
      chickens with B A9/A9 and B A9/A4 MHC genotypes, respectively, and seroconversion
      in six other genotypes was 19% (10/53). These differences among MHC genotypes for
      specific seroconversion rate were not statistically significant. CAV genomes were
      detected in the thymus of 87.7% (93/110) of the inoculated birds with no
      statistically significant differences between MHC genotypes. Mild thymic
      lymphocytolysis, lymphedema, and medullary hemorrhage were observed in the
      inoculated chickens. Histomorphometric analysis showed that cortical lymphocyte
      to-parenchyma ratios did not differ between inoculated and uninoculated groups or
      among MHC genotypes. Similar findings have been reported previously in white
      leghorn chickens of similar age, suggesting that broilers show a similar
      resistance to the effects of CAV infection at this age. The absence of
      significant clinical and pathological changes in the orally inoculated broilers
      at this age contrasts with CAV-associated thymus damage seen frequently in
      condemned commercial broilers at harvest.

PMID- 16404989
TI  - Molecular characterization of avian infectious bronchitis virus strains isolated
      in Colombia during 2003.
AB  - Sixteen infectious bronchitis virus (IBV) isolates were recovered from broilers
      and layers from five geographic poultry regions in Colombia. The viruses were
      isolated from tracheas, lungs, and cecal tonsils of birds, previously vaccinated
      with the Massachusetts strain, that were showing respiratory signs. Further
      analysis of the IBV isolates was achieved by phylogenetic analysis comparing
      their deduced amino acid sequences in the hypervariable region 1 of the S1 gene
      with reference strains. Four unique genotype clusters containing isolates with
      indigenous genotypes were observed. One isolate was found to be the Connecticut
      genotype and three isolates were found to be the Massachusetts genotype.

PMID- 16404988
TI  - Detection of antibodies to the nonstructural protein (NS1) of avian influenza
      viruses allows distinction between vaccinated and infected chickens.
AB  - To differentiate avian influenza virus (AIV)-infected chickens vs. chickens
      immunized with inactivated avian influenza virus, an enzyme-linked immunosorbent
      assay (ELISA) was developed using a recombinant nonstructural protein (NS1) as
      the diagnostic antigen, which was cloned from an AIV H9N2 subtype strain isolated
      during the avian influenza outbreak of 2003-04 and expressed in Escherichia coli.
      Antibodies to the AIV NS1 protein was only detected in the sera of chickens
      experimentally infected with AIV but not in the sera of chickens immunized with
      inactivated vaccine. This ELISA is useful for serological diagnosis to
      distinguish chickens infected with influenza viruses from those immunized with
      inactivated vaccine.

PMID- 16404990
TI  - Genotyping of infectious bursal disease virus strains by restriction fragment
      length polymorphism analysis of the VP1, VP2, and VP3 genes.
AB  - SUMMARY. This study aimed to genotype infectious bursal disease virus (IBDV)
      isolates from the Minas Gerais state poultry industry. RNA was extracted from
      bursae obtained from field cases without passage or commercial vaccines. Genetic
      subtyping of IBDV isolates and vaccine strains was carried out by the reverse
      transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length
      polymorphism (RFLP) analysis. A 588-bp fragment in the VP1 gene, an 847-bp
      fragment in the VP2 gene, and a 320-bp fragment in the VP3 gene were amplified by
      PCR and digested with restriction enzymes PstI and ScaI (VP1); BamHI, BstEII, and
      PstI (VP2); and NcoI, ScaI, and XbaI (VP3). Our work shows that complementing the
      clinical history of the outbreaks with RT-PCR followed by RFLP analysis using
      PstI for VP1, BamHI for VP2, and XbaI for VP3 allowed an accurate classification
      of a causative agent as a very virulent IBDV.

PMID- 16404991
TI  - Mycoplasma gallisepticum hemagglutinin V1hA, pyruvate dehydrogenase PdhA, lactate
      dehydrogenase, and elongation factor Tu share epitopes with Mycoplasma imitans
      homologues.
AB  - Mycoplasma gallisepticum is a major pathogen of poultry. Mycoplasma imitans is
      genetically and antigenically closely related to M. gallisepticum, but so far,
      only a few proteins of M. imitans have been identified as sharing epitopes with
      M. gallisepticum. In this study, we identified three proteins of M. gallisepticum
      that share with M. imitans epitopes defined by monoclonal antibodies (MAbs). MAb
      9D4 reacted with the 67-kD hemagglutinin V1hA (previously termed pMGA) of M.
      gallisepticum and with its continuously expressed 40-kD protein. This MAb also
      reacted with a 40-kD protein of M. imitans, but not with its putative V1hA. Two
      dimensional (2D) immunoblots of M. gallisepticum strains showed that their 40-kD
      proteins reacting with MAb 9D4 are expressed as major forms with isoelectric
      points (pI) around 6, and also as less-abundant forms differing in pI. In M.
      imitans, major forms of 40-kD proteins recognized by MAb 9D4 had pI around 6,
      whereas minor forms had pI between 5.5 and 5.8. The N-terminal sequence of the M.
      gallisepticum 40-kD protein recognized by MAb 9D4 strongly indicates that this
      protein is pyruvate dehydrogenase E1, subunit alpha (PdhA protein, also termed
      AcoA). The position of elongation factor Tu (EF-Tu), detected by the reference
      MAb GB8, was very similar in the 2D proteome maps of M. gallisepticum and M.
      imitans (MW of about 45 kD; pI - 5.6). In both M. gallisepticum and M. imitans,
      MAb 7G1 reacted with proteins of about 36 kD with similar charges (major forms
      with pI of about 8). The position of this protein in the proteome map of M.
      gallisepticum and its N-terminal sequence strongly suggest that MAb 7G1
      recognizes lactate (malate) dehydrogenase (Ldh or Mdh). Comparison of 2D
      proteomes of 10 M. gallisepticum strains indicated that positions of EF-Tu, PdhA,
      and Ldh proteins are rather consistent and can be used as reference points in
      further analyses of the M. gallisepticum proteome.

PMID- 16404992
TI  - Molecular characterization of the capsid gene of two serotypes of turkey
      astroviruses.
AB  - Astrovirus infections mainly cause acute gastroenteritis in children and young
      animals. Human astroviruses are well characterized antigenically and genetically.
      However, information on turkey astroviruses is limited. We isolated two
      astroviruses (TAstV1987 and TAstV2001) from turkeys and classified them as two
      different serotypes using a virus neutralization test. To elucidate the
      differences between these two isolates at the molecular level, further genetic
      characterization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) analysis were carried out. The sequences of the complete capsid
      protein gene of these two isolates were obtained by cloning and sequencing. The
      percentage nucleotide and predicted amino acid identities for these two sequences
      along with those of 16 other capsid protein gene sequences from human and animal
      astroviruses retrieved from GenBank were calculated using MegAlign. The results
      showed that TAstV1987 and TAstV2001 had 73.3% nucleotide and 82.8% amino acid
      identities, respectively. An unrooted Neighbor-joining phylogenetic tree of these
      sequences was generated using MEGA 3 software with 1000 bootstrap replicates. The
      results of evolutionary analysis showed that TAstV1987 was closely related
      genetically to another virus, designated TAstV-2, whereas TAstV2001 was not as
      close to TAstV-2 as TAstV1987. The analysis of the capsid proteins of the two
      viruses by SDS-PAGE revealed that they had different band patterns, indicating
      that their capsid proteins consisted of different viral proteins. The findings in
      this study revealed the molecular differences in the capsid protein gene of
      TAstV1987 and TAstV2001, which may provide the molecular basis of the antigenic
      differences between these two serotypes of turkey astroviruses.

PMID- 16404993
TI  - Emergence of a virulent type C avian metapneumovirus in turkeys in Minnesota.
AB  - The objectives of the present study were to investigate the pathogenesis of a
      recent isolate of avian metapneumovirus (aMPV) in turkeys and to evaluate the
      quantitative distribution of the virus in various tissues during the course of
      infection. Seventy 2-week-old turkey poults were divided equally into two groups.
      One group was inoculated with aMPV (MN 19) with a titer of 10(5.5) TCID50
      oculonasally. Birds in the second group were maintained as sham-inoculated
      controls. Birds showed severe clinical signs in the form of copious nasal
      discharge, swollen sinus, conjunctivitis, and depression from 4 days
      postinoculation (PI) to 12 days PI. Samples from nasal turbinates, trachea,
      conjunctiva, Harderian gland, infraorbital sinus, lungs, liver, and spleen were
      collected at 1, 3, 5, 7, 9, 11, and 14 days PI. Histopathologic lesions such as a
      multifocal loss of cilia were prominent in nasal turbinate and were seen from 3
      to 11 days PI. Immunohistochemistry revealed the presence of aMPV from 3 to 9
      days PI in nasal turbinate and trachea. Viral RNA could be detected for 14 days
      PI from nasal turbinate and for 9 days from trachea. In situ hybridization
      demonstrated the presence of aMPV from 1 to 11 days PI in nasal turbinates and
      from 3 to 9 days PI in the trachea. Quantitative real-time polymerase chain
      reaction data showed the presence of a maximum amount of virus at 3 days PI in
      nasal turbinate and trachea. Clinically and histopathologically, the new isolate
      appears to be more virulent compared to the early isolates of aMPV in the United
      States.

PMID- 16404994
TI  - Comparison of prophylactic or therapeutic dietary administration of capsaicin for
      reduction of Salmonella in broiler chickens.
AB  - In three experiments the effects of prophylactic or therapeutic dietary inclusion
      of capsaicin, the pungent component of peppers, were evaluated as a nonantibiotic
      alternative for reduction of Salmonella in broiler chickens through culture and
      morphologic assessment of cecal tissue. Expt. 1 evaluated the effects of 0 or 10
      ppm purified capsaicin (CAP) in the starter phase (days 1-16) on chicks
      challenged with Salmonella Enteritidis (SE) on day of age. Therapeutic inclusion
      of 10 ppm purified CAP increased (P < 0.05) liver/spleen (L/S) and ceca positive
      results for SE. In Expt. 2, capsaicin oleoresin (CO) was included in the finisher
      diet (days 30-37) at 0, 5, or 20 ppm with SE challenge on day 31. Inclusion of 5
      ppm CO increased ceca positive results for SE, and a linear decrease in cecal
      lamina propria thickness of SE-challenged birds was observed with increased CO
      concentration in the diet. Expt. 3 evaluated prophylactic CO treatment at 0, 5,
      or 20 ppm in starter, grower, and finisher diets for resistance to SE or
      Salmonella Typhimurium (ST) challenge on day 14 or 29. With challenge on day 14,
      5 and 20 ppm prophylactic CO feeding reduced ceca SE positive results by 37% and
      26%, respectively, and ST culture rate was reduced similarly with 5 ppm CO.
      Lamina propria thickness of the ceca increased with 5 ppm CO feeding in SE
      challenged birds, whereas a decrease was observed in nonchallenged birds fed 5
      ppm CO. Challenge on day 29 of birds fed 20 ppm CO resulted in reduced L/S
      positive results for SE. Lamina propria thickness decreased with 5 ppm CO and SE
      or ST challenge compared with nonchallenged birds fed 5 ppm. An increase was
      observed in ST- or SE-challenged birds fed 20 ppm CO compared with nonchallenged
      birds fed 20 ppm CO. No differences were observed in mast cell number in either
      Expt. 2 or 3. These data provide evidence that prophylactic or therapeutic
      dietary capsaisin differentially affects broiler susceptibility to Salmonella.

PMID- 16404995
TI  - Detection of infectious bursal disease virus in various lymphoid tissues of
      experimentally infected specific pathogen free chickens by different reverse
      transcription polymerase chain reaction assays.
AB  - Infectious bursal disease (IBD) is a worldwide distributed immunosuppressive
      viral disease in young chickens, controlled by vaccination. Emergence of several
      strains of IBD virus (IBDV) has created a demand for strain-specific diagnostic
      tools. In the present experiment, five different reverse transcription polymerase
      chain reaction (RT-PCR) assays, including two recently developed strain-specific
      assays, were employed for detection of ribonucleic acid (RNA) from three
      different IBDV strains in bursa tissue samples from experimentally infected
      specific pathogen free chickens. The virus strains included vaccine strain D78,
      classical strain Faragher 52/70, and the very virulent Danish strain DK01. The
      presence of the virus infection was confirmed by histopathologic evaluation of
      bursa lesions. The largest number of positive samples was obtained with a strain
      specific two-step multiplex (MPX) RT-PCR assay based on iScript enzyme, and the
      commercially available Qiagen one-step RT-PCR. Between these methods, agreement
      was obtained for 57 of 59 samples. Because the Qiagen one-step RT-PCR assay was
      suggested as the more sensitive of these two assays, it was used for detection of
      IBDV in bone marrow, spleen, thymus, and cecal tonsils from experimentally
      infected chickens. The identity of the virus strains involved was confirmed by
      MPX RT-PCR. In conclusion, the MPX RT-PCR represented a reliable assay for
      detection and differentiation of IBDV strains in selected lymphoid tissues of
      chickens. All three of the IBDV strains used were detected in bursa tissues,
      whereas only the two virulent strains were detected in bone marrow, spleen, and
      thymus.

PMID- 16404996
TI  - Effect of IBV-H120 vaccination in broilers on colibacillosis susceptibility after
      infection with a virulent Massachusetts-type IBV strain.
AB  - Vaccination against infectious bronchitis (IB) is aimed to protect against
      clinical IB. The question is, however, whether vaccinated birds are also
      protected against predisposure for colibacillosis after a subsequent IBV
      infection. We examined this research question in four experiments. One-day-old
      commercial broilers, housed in isolators, were vaccinated with IB vaccine strain
      H120 by coarse spray or ocularly. Twenty-eight days after vaccination, broilers
      were challenged with the virulent IBV strain M41. Five days later, broilers were
      inoculated with Escherichia coli strain 506. Body weight uniformity, severity of
      E. coli airsacculitis, and systemic E. coli infection at 7 days following E. coli
      inoculation were used as parameters for colibacillosis. IBV vaccination reduced
      both the number of broilers with E. coli airsacculitis as well as the severity of
      airsacculitis significantly after challenge with IBV-M41 and E. coli 506.
      However, in spray-vaccinated groups, no significant reduction of the number of
      birds with systemic colibacillosis or the severity of this infection was
      obtained, and body weight uniformity was not significantly improved compared with
      nonvaccinated, IBV-M41, and E. coli 506-challenged groups. Eye-drop vaccination
      resulted in conflicting results.

PMID- 16404997
TI  - Molecular characterization and phylogenetic analysis of Newcastle disease virus
      isolates from healthy wild birds.
AB  - Wild waterfowl is considered a natural reservoir of potentially infectious agents
      and a source of pathogenic viruses like avian paramyxoviruses type 1 (APMV 1). In
      1997, commercial poultry in Argentina had reached the status of being free from
      virulent Newcastle disease virus (NDV) infections. Vaccination and biosecurity
      measures are actively performed to maintain this preferential sanitary condition.
      However, the risk of reintroduction of pathogenic viruses is always present. In
      this context, we conducted a study to describe the status of wild healthy birds
      in a geographic region relevant for the poultry industry. The presence of anti
      NDV antibodies was determined in different species in all areas sampled
      suggesting previous contact with NDV. Seven ND viruses were isolated and
      characterized as apathogenic strains by biological and molecular methods. The
      phylogenetic analysis revealed that the majority of the Argentinian isolates form
      a subgroup related to viruses of genotype II. The results presented here
      highlight the importance of maintaining strict biosecurity measures and
      vaccination programs in poultry industries in order to preserve the virulent NDV
      free status for commercial flocks in the country.

PMID- 16404998
TI  - Respiratory infection of turkeys with Listeria monocytogenes Scott A.
AB  - The pathogenesis of L. monocytogenes strain Scott A was studied by challenging
      day-old male turkey poults by air sac inoculation with tryptose phosphate broth
      containing 10(0) cfu (control), 10(4), 10(5), and 10(6) cfu (low challenge), or
      10(7) and 10(8) cfu (high challenge) of the Scott A (serotype 4b) strain of L.
      monocytogenes. Mortality at 2 wk postinfection (PI) ranged from 25% for low
      challenge to 100% for high challenge (P= 0.0001). Gross and histopathological
      lesions were observed in heart, liver, spleen, lung, and bursa of Fabricius of
      mortalities at 4 days PI. Listeria monocytogenes challenge resulted in
      significantly decreased relative weight of the bursa of Fabricius and increased
      relative weight of the spleen, and L. monocytogenes was isolated by direct
      plating of liver, pericardium, brain, and both left and right stifle joint
      synovium (knee) cultures, as well as gall bladder, yolk sac, and cecal tonsil
      from transfer swabs onto Listeria-selective agar. Isolates were confirmed as
      positive using Gram stain, biochemical tests, and the Biolog system. High
      challenge resulted in confirmed L. monocytogenes isolation from 48% of left knee
      and 59% of right knee cultures. Low challenge resulted in isolation of L.
      monocytogenes from 11% of both left and right knee cultures. These results
      suggest that L. monocytogenes Scott A colonization of turkey knee synovial tissue
      can initiate in day-of-age poults and that L. monocytogenes Scott A can be
      invasive through air sac infection.

PMID- 16404999
TI  - An allele-specific PCR assay for the rapid and serotype-specific detection of
      Salmonella pullorum.
AB  - Salmonella serovar Pullorum is a causative agent of pullorum disease (PD) in
      poultry and is responsible for severe economic losses to the poultry industry in
      many parts of the world. A definitive detection of Pullorum requires culture
      followed by serotyping and biochemical identification, a process that is tedious
      and takes several weeks to accomplish. We have developed a rapid allele-specific
      polymerase chain reaction (PCR) method based on the nucleotide polymorphism in
      rfbS gene sequence for the serotype-specific detection of Pullorum and its
      differentiation from the closely related Gallinarum. The specificity of this PCR
      assay was tested using DNA samples from Pullorum (n = 13), Salmonella serotypes
      other than Pullorum (n = 19), and closely related non-Salmonella organisms (n =
      5). The PCR assay was highly serotype-specific as the PCR amplicon of 147 base
      pairs was observed only in the case of Pullorum, while all the other DNA samples
      tested PCR negative. A definitive identification of Pullorum cultures was
      possible in less than 3 hr. As little as 100 pg of SP DNA was detected. This
      allele-specific PCR method is highly specific as well as sensitive and may be an
      effective molecular tool in the rapid and serotype-specific detection of Pullorum
      and differentiation from other Salmonella species.

PMID- 16405000
TI  - Construction of influenza virus siRNA expression vectors and their inhibitory
      effects on multiplication of influenza virus.
AB  - Three plasmid constructs were prepared that express small interfering RNAs
      (siRNAs) targeted to sequences encoding the ribonucleoprotein member,
      nucleoprotein (NP) and/or PA, of influenza virus genome. The antiviral properties
      of siRNAs against the H5N1 strain of influenza virus were studied by evaluating
      their capacity to silence expression of target genes as well as their effect on
      influenza virus-induced apoptosis in Madin-Darby canine kidney cells, chicken
      embryo fibroblast cells, and embryonated chicken eggs in a transient replication
      model. The results demonstrated that all three siRNAs expressing plasmids
      efficiently transcribed the short hairpin RNAs and inhibited expression of the NP
      or PA proteins measured by northern blot and western blot analyses, respectively,
      in the transfected cells. We also found that the integrated siRNA expression
      plasmid pEGFP/NP+PA, which we constructed for the first time to synchronously
      target NP and PA segments of the influenza virus genome, could more efficiently
      inhibit synthesis of influenza virus detected by cytopathogenic effects,
      hemagglutinin, and plaque-forming unit assays in the transfected cells.
      Furthermore, the integrated siRNA expression plasmid pEGFP/NP+PA could remarkably
      interrupt the cellular apoptotic course caused by influenza virus, which
      protected infected cells from apoptotic damage. In contrast, a control siRNA
      expression plasmid, pEGFP/HK, could neither inhibit the protein expression and
      production of influenza virus nor interrupt the cell apoptotic course mediated by
      influenza virus. These results demonstrate that RNA interference (RNAi) can be
      used to inhibit protein expression and replication of influenza virus and that
      RNAi treatment holds potential as a new approach to prevent avian influenza.

PMID- 16405001
TI  - Investigations on the pathogenicity of Erysipelothrix rhusiopathiae in laying
      hens.
AB  - Erysipelas was diagnosed in 1998 from 34-wk-old laying hens in a free range flock
      in Germany. Erysipelothrix rhusiopathiae of serotype 1 was cultured from internal
      organs of the affected birds. This article describes the pathogenicity of the
      field isolate of E. rhusiopathiae in experimentally infected specific pathogen
      free (SPF) laying hens. Three experiments were performed with SPF chickens
      inoculated at 17, 27, and 37 wk of age by either intramuscular (IM) or oral
      route. Inoculated birds were observed for 14 days. The highest mortality rates
      occurred in older birds, with 100% mortality observed in the 37-wk-old birds
      inoculated IM, 60% mortality reported in the younger 27-wk-old birds, and no
      mortality in the 17-wk-old age group. In the orally infected 27-wk-old birds, 40%
      mortality was detected, whereas no mortality was observed in the oldest birds by
      the same route. The results of the experiments support the contention that older
      birds are more sensitive to infection than younger birds and that mortality in
      laying hens is age related and dependent on the route of infection.

PMID- 16405002
TI  - Recovery of Campylobacter jejuni in feces and semen of caged broiler breeder
      roosters following three routes of inoculation.
AB  - We previously reported the recovery of Campylobacter (naturally colonized) from
      the ductus deferens of 5 of 101 broiler breeder roosters, and four of those five
      positive roosters had previously produced Campylobacter-positive semen samples.
      Those results prompted further evaluation to determine if inoculation route
      influenced the prevalence or level of Campylobacter contamination of semen, the
      digestive tract, or reproductive organs. Individually caged roosters, confirmed
      to be feces and semen negative for Campylobacter, were challenged with a marker
      strain of Campylobacter jejuni either orally using 1.0 ml of a diluted cell
      suspension (log(10)4.3 to 6.0 cells), by dropping 0.1 ml of suspension
      (log(10)5.3 to 7.0 cells) on the everted phallus immediately after semen
      collection or by dip coating an ultrasound probe in the diluted cell suspension
      (log(10)4.3 to 6.0 cells) and then inserting the probe through the vent into the
      colon. Six days postinoculation, individual feces and semen samples were again
      collected and cultured for Campylobacter. Seven days postinoculation, roosters
      were killed, the abdomen aseptically opened to expose the viscera, and one cecum,
      one testis, and both ductus deferens were collected. The samples were then
      suspended 1:3 (weight/volume) in Bolton enrichment broth for the culture of
      Campylobacter. Samples were also directly plated onto Cefex agar to enumerate
      Campylobacter. Campylobacter was recovered 6 days after challenge from feces in
      82% of samples (log(10)4.1 colony-forming units [CFU]/g sample), 85% of semen
      samples (log(10)2.9 CFU/ml), and on the seventh day postchallenge from 88% of
      cecal samples (log(10)5.8 CFU/g sample). Campylobacter was not directly isolated
      from any testis sample but was detected following enrichment from 9% (3/33) of
      ductus deferens samples. Roosters challenged with Campylobacter orally, on the
      phallus, or by insertion of a Campylobacter dip-coated ultrasound probe were all
      readily colonized in the ceca and produced Campylobacter-positive semen and feces
      on day 6 after challenge. The low prevalence of recovery of Campylobacter from
      the ductus deferens samples and failure to recover from any testis sample
      suggests that semen may become Campylobacter positive while traversing the cloaca
      upon the everted phallus. The production of Campylobacter-positive semen could
      provide a route in addition to fecal-oral for the horizontal transmission of
      Campylobacter from the rooster to the reproductive tract of the hen.

PMID- 16405003
TI  - Experimental assessment of the pathogenicity of H5N1 influenza A viruses isolated
      in Japan.
AB  - We examined the pathogenicity for chickens of two H5N1 avian influenza viruses
      isolated in Japan, A/chicken/ Yamaguchi/7/2004 (Ck/Yamaguchi/7/04) isolated from
      outbreaks in commercial layer chickens, and A/duck/Yokohama/aq10/ 2003
      (Dk/Yokohama/aq10/03) isolated from duck meat imported from China. All chickens
      inoculated intranasally with either strain died, and the viruses were reisolated
      from all organs examined. However, both the mean time of onset of clinical signs
      and the mean death time of Ck/Yamaguchi/7/04 were shorter than those of
      Dk/Yokohama/aq10/03.

PMID- 16405004
TI  - Protection conferred by bivalent and trivalent infectious coryza bacterins
      against prevalent serovars of Avibacterium (Haemophilus) paragallinarum in
      Mexico.
AB  - The protection and level of hemagglutination-inhibition (HI) antibodies conferred
      in infectious coryza bivalent- and trivalent-immunized chickens against
      Avibacterium (Haemophilus) paragallinarum field isolates of the prevalent
      serovars in Mexico (A-1, A-2, B-1, and C-2) were investigated. The bivalent
      bacterin (A-1 and C-1) conferred significant protection and increased HI
      antibodies against isolates of serovars A-1, A-2, and C-2, but not against a
      serovar B-1 isolate. The trivalent bacterin (A-1, B-1, and C-2) conferred
      protection and increased HI antibodies against all four of the isolates. The
      results confirmed that in poultry areas where serovar B-1 is prevalent, the
      inclusion of this serovar in bacterins is needed to confer protection against
      infectious coryza caused by A. (H.) paragallinarum isolates of serovar B-1.

PMID- 16405005
TI  - Evaluation of the protection conferred by a disinfectant against clinical disease
      caused by Avibacterium paragallinarum serovars A, B, and C from Argentina.
AB  - This work evaluates the efficiency of the administration of the disinfectant N
      alkyl dimethyl benzyl ammonium chloride (TIMSEN) in the prevention of the
      horizontal transmission of serovars A, B, and C of Avibacterium paragallinarum,
      the causative agent of avian infectious coryza. This disinfectant was
      administered in drinking water (50 ppm) and once or twice per day by coarse spray
      (800 ppm, 8 ml per m3 during 3 seconds). In three trials conducted with
      vaccinated birds, the disinfectant reduced the clinical signs of infectious
      coryza significantly (P < 0.05). There was no significant effect when the product
      was used in a fourth trial with unvaccinated birds. Furthermore, the application
      of only one daily environmental spraying was sufficient to significantly reduce
      clinical signs. According to these results, in order to diminish the clinical
      signs of infectious coryza in birds vaccinated against A. paragallinarum, it is
      recommended to administer this disinfectant in drinking water and by
      environmental spraying.

PMID- 16405006
TI  - Individual and combined effects of Fusarium moniliforme culture material,
      containing known levels of fumonisin B1, and Salmonella gallinarum infection on
      liver of Japanese quail.
AB  - Three hundred day-old Japanese quail (Coturnix coturnix japonica) were divided
      into two groups with 150 quail in each group. One group was maintained on quail
      mash alone, while Fusarium moniliforme culture material was added to quail mash
      in the second group from day 5 of age and was supplied at a rate of 150 ppm
      fumonisin B1 (FB1)/kg mash. At day 21, each group was further subdivided into two
      groups, yielding four groups with 75 birds apiece, which served as the control
      (group CX), the Salmonella Gallinarum alone group (group CS), the FB1 alone group
      (group FX), and the group fed FB1 and infected with Salmonella Gallinarum (group
      FS). An oral challenge with Salmonella Gallinarum organisms (2 x 10(4) colony
      forming units/ml) was given to groups CS and FS at 21 days of age. Three quail
      each were necropsied on day 21 (0 day interval) from groups CX and FX only. At
      subsequent intervals (i.e., 1, 2, 3, 5, 7, 10, 14, and 21 days postinfection
      [DPI]), three quail were euthanatized from all four groups (CX, CS, FX, and FS).
      The gross and microscopic lesions were recorded in both mortality and
      euthanatized birds at the above intervals. The ultrastructural studies were done
      at 5 DPI. Mild to moderate hepatomegaly and pale discoloration of liver were
      observed in group FX, while congestion, hemorrhages, necrosis, and mild to severe
      hepatomegaly were the predominant gross lesions in both infected groups (CS and
      FS). The gross lesions in quail inoculated with Salmonella Gallinarum alone
      (group CS) generally developed slowly, appeared more widely scattered, and
      involved comparatively less surface area in contrast to the rapidly progressive
      and frequently confluent lesions in the combination group (FS), especially in the
      first 5 days of infection. Mild to marked hepatocellular swelling, multifocal
      hepatic necrosis, and hepatocellular and bile duct hyperplasia were the
      characteristic microscopic changes in the FX group. Microscopic lesions in quail
      of group CS comprised congestion, vacuolar changes, and focal necrosis in early
      stages, followed by granulomatous lesions at later intervals. Similar but more
      severe lesions were observed in the combination group (FS). Based on transmission
      electron microscopy, the maximum effect of FB1 toxicity was observed on
      mitochondria and endoplasmic reticulum. In general, the mitochondriae showed
      diverse form and structure, some of which appeared to lose their intact outer
      membrane, and the mitochondrial cristae were disoriented. The deformity in the
      cisternae structure of rough endoplasmic reticulum, with their rearrangement into
      round or tubular forms either bearing granular surface or leading to accumulation
      of smooth endoplasmic reticulum, was evident only in groups FX and FS. We
      conclude that the continuous presence of fumonisins in the diets of young quail
      might increase their susceptibility to or the severity of Salmonella Gallinarum
      infection.

PMID- 16405007
TI  - Phylogenetic analysis of avian poxviruses among free-ranging birds of Virginia.
AB  - Polymerase chain reaction was used to amplify a portion of the avian poxvirus
      core 4b gene of infected free-ranging birds that presented at the Wildlife Center
      of Virginia during the 2003 and early 2004 years. The species of bird infected
      were a great blue heron (Ardea herodias), two American crows (Corvus
      brachyrhyncos), two American robins (Turdus migratorius), two mourning doves
      (Zenaida macroura), a red-tailed hawk (Buteo jamaicensis), a blue-gray
      gnatcatcher (Polioptila caerulea), a northern mockingbird (Mimus polyglottos), a
      house finch (Carpodacus mexicanus), and a northern cardinal (Cardinalis
      cardinalis). Phylogenetic analysis was performed using the consensus sequences
      determined for each avian case in Virginia in combination with avian poxvirus
      core 4b gene sequence from isolates previously described in Europe and that of
      vaccinia virus. Alignment of DNA sequences identified areas of point mutations
      and, in the case of a single mourning dove, the incorporation of a triplet of
      nucleotides. Maximum-likelihood analysis grouped the 2003-2004 Virginia avian
      poxviruses into a clade distinct from those reported in European free-ranging
      birds, with the exception of a single case in a mourning dove that clustered
      within one European clade. The cladogram that resulted from our analysis of the
      European isolates is in agreement with those previously published. This study
      identified a distinct clade of avian poxvirus unique from four clades previously
      described and associated with epornitics in free-ranging birds, where the core 4b
      gene DNA sequence has been the basis of comparison.

PMID- 16405008
TI  - Ulcerative enteritis (quail disease) in lories.
AB  - Ulcerative enteritis is found in a wide range of avian hosts but has not been
      described in psittacine birds. This case report describes ulcerative enteritis in
      four lories (two Trichoglossus sp. and two Eos sp.) that were found dead without
      any previous sign of disease. Macroscopically, all four birds showed good body
      condition. The only remarkable finding was a moderate dilatation of the small
      intestine with the presence of multiple yellow foci. Histologically, multiple
      ulcers extended into the submucosa and were filled with necrotic debris; bacteria
      and fibrin were observed in the intestinal mucosa. The liver and spleen exhibited
      a multifocal fibrinoid necrosis associated with a very moderate inflammatory
      reaction. Microbiological isolation revealed colonies of Clostridium colinum and
      Clostridium perfringens in the intestinal tract of the investigated birds.

PMID- 16405010
TI  - Data from 11 years of molecular typing infectious bronchitis virus field
      isolates.
AB  - In 1993, a new molecular typing method for infectious bronchitis virus (IBV) was
      introduced. This method uses reverse transcriptase-polymerase chain reaction (RT
      PCR) and restriction fragment length polymorphism (RFLP) analysis of the spike
      gene to obtain RFLP patterns that correlate with serotype. Using that test at the
      Poultry Diagnostic and Research Center (PDRC, University of Georgia, Athens, GA),
      we have identified a total of 1523 IBV isolates in the past 11 yr. The data were
      obtained from clinical samples submitted to our laboratory from birds with
      clinical signs characteristic of IBV infection. The samples are primarily from
      the southeastern United States but are also from many other states as well as
      from outside the United States. Most of the isolations occurred during July,
      followed by May, April, November, October, and January. The fewest number of
      isolates identified on an annual basis was 20 in 2003. An unusually high number
      of isolations occurred in 1997 (318 isolations) and 1999 (246 isolations), which
      coincided with the GAV variant virus and GA98 variant virus outbreaks
      respectively. By far, the Ark-DPI strain was the most frequently identified type
      of IBV and ranged from 23% to 65% of total isolations per year. Ark-like
      isolates, defined as having a similar but unique RFLP pattern from the Ark-DPI
      vaccine strain were identified every year of the study except in 1996. In
      addition, new Ark-like isolates continued to emerge each year (except in the year
      2000) beginning in 1997, reflecting the ability of that IBV type to undergo
      genetic drift. Eighty-two different variant viruses were identified although only
      two (GAV and GA98) became persistent and caused widespread disease. Some viruses
      tended to be geographically restricted to a given area (CAV in California and
      MX97-8147 in Mexico), whereas others were widespread (Ark-DPI, Conn, DE072, and
      Mass). The Florida, Gray, Holte, Iowa, and JMK types were not detected during the
      11-yr period, and no foreign virus types were detected in the United States.
      These data show that IBV variant viruses are consistently circulating in
      commercial poultry and are capable of causing disease outbreaks. Our observations
      highlight the importance of constantly monitoring IBV as well as other
      coronaviruses like severe acute respiratory syndrome-coronavirus that have the
      ability to change and emerge to cause disease in a susceptible host.

PMID- 16405009
TI  - Cecal spirochetosis caused by Brachyspira pilosicoli in commercial turkeys.
AB  - Spirochetes that were identified as Brachyspira pilosicoli were present in the
      ceca of 7.5- to 18-wk-old turkeys with cecal spirochetosis and typhlitis. The
      identity of B. pilosicoli was confirmed on the basis of ultrastructural
      morphology of the cecal epithelium adherent microbes, immunohistochemical
      staining with a Brachyspira genus-specific monoclonal antibody, and amplification
      of a B. pilosicoli species-specific 16S ribosomal RNA (rrs gene) sequence by
      using the polymerase chain reaction and DNA obtained by laser-capture
      microdissection of the epithelium-adherent microbial fringe. To the author's
      knowledge, this is the first report of B. pilosicoli in the ceca of turkeys.

PMID- 16405012
TI  - [Diagnosis of anaplastic large-cell lymphoma].
AB  - Principles of morphological diagnosis of anaplastic large-cell lymphoma (ALCL)
      are considered, several its variants are distinguished: classic (32 cases), small
      cell (4 cases), rich in granulocytes (2 cases) and lymphohistiocytic (1 case).
      ALK expression was variable: 93% at the age up to 20, 60% at the age from 20 to
      40 years, none at the age 40 years and older. Morphological similarities between
      ALCL, classic variants of Hodgkin's lymphoma, variants of diffuse large B-cell
      lymphoma may require immunohistochemical investigation the criteria of which are
      suggested.

PMID- 16405013
TI  - [Askenazi (Hurtle) cell tumors of the thyroid].
AB  - Oncocytic adenomas have primarily follicular structure; trabeculas, solid areas,
      necrosis are rare. They may possess malignant potential as their malignant
      transformation occurs in 35% cases against 5% in adenomas of follicular cells.
      Oncocytic follicular carcinomas can be hardly distinguished from oncocytic
      adenomas. Tumors larger than 4-5 cm in diameter are considered to be malignant.
      Main difference with adenomas is invasion into the capsule surrounding thyroid or
      into the vessels. They can be well or poorly differentiated or anaplastic.
      Oncocytic papillary carcinoma and oncocytic medullary carcinoma are rare. The
      clinical course of oncocytic tumors is more aggressive than that of tumors from
      follicular cells. Of key importance in differential diagnosis is electron
      microscopy (EM) and immunohistochemistry with antimitochondrial antibodies. EM
      may be also useful in determination of the degree of oncocytic tumors maturation.

PMID- 16405015
TI  - [Influence of anthropogenic pollution on thyroid structure in Perm population].
AB  - The comparison of the thyroid structure in 73 Perm sitizens who died in the 1960s
      with that of 59 citizens who died in the 2000s revealed in the latter group
      symptoms of "tissue maladaptation" (retention of follicular colloid with cystic
      transformation of the follicles, lymphoplasma cell infiltration with oxyfilic
      thyrocytes transformation into B-cells, appearance of areas with a rough
      connective tissue in colloidrhagia and edema with capillary collapse, calcium
      deposits into the vessels and stroma). It is proven that these morphological
      changes are due to the effects of xenobiotics. Pronounced increase of heavy
      metals deposits in the thyroid by the 2000s was reported. Such thyroid
      pathomorphosis inevitably results in hypothyroidism.

PMID- 16405014
TI  - [Insullar cancer. Diagnosis and place in the structure of thyroid carcinoma].
AB  - 15 cases of thyroid insullar carcinoma in patients aged from 10 to 65 years are
      described. It is shown that the tumor has aggressive histological signs and
      represents a prognostically important form of thyroid carcinoma.

PMID- 16405016
TI  - [Quantitative immunohistochemical tenascin test in infiltrative duct breast
      cancer].
AB  - 27 cases of infiltrative duct breast carcinoma have been studied
      immunohistochemically. A significant correlation was found between an increase of
      structures containing tenascin and an increase of tumor metastatic activity.

PMID- 16405018
TI  - [Morphofunctional characteristics of microvessels in serous tumors of the
      ovaries].
AB  - High vascularization is noted in serous papillary ovarian tumors of a low
      malignancy grade, particularly in malignant serous ovarian tumors with low
      vascularization in benign neoplasms. Pronounced morphological changes in the
      vascular wall are found mainly in malignant tumors and tumors of a low malignancy
      grade where primitive blood vessels of a sinusoid type with a thin muscle wall
      prevail. Types of vascularization in the tumors studied are variable and this
      correlates with results of color doppler mapping.

PMID- 16405017
TI  - [Expression of E-cadherine as a differential diagnostic fest for lobular
      infiltrative breast cancers].
AB  - An immunomorphological study of 30 breast carcinomas was conducted. In accordance
      with the histological characteristics they had been previously diagnosed as
      lobular infiltrative carcinomas (LIC). We have studied E-cadherin cell-cell
      adhesion molecules and also epithelial markers and basement membranes. We have
      analyzed the cryostate and paraffin sections of in situ structures, invasion
      components and metastases. E-cadherin staining was negative, positive or mixed.
      The E-cadherin negative group consisted of 17 carcinomas of classic LIC
      accompanied with dyshesive invasion. The E-cadherin positive group consisted of 6
      carcinomas. According to our results this diagnosis was changed to ductal
      infiltrative carcinoma. The E-cadherin mixed group consisted of 7 special type
      carcinomas with double lobular-ductal differentiation, which had in situ
      structures of negative or positive cells. In these cases in situ structures
      consisting of both E-cadherin negative and positive parts were also observed. It
      is shown that E-cadherin expression can be used in doubtful cases in order to
      differentiate between the lobular and ductal forms of breast carcinoma.

PMID- 16405019
TI  - [Intraductal intraepithelial neoplasia and ductal pancreatic carcinoma].
AB  - The review of modern achievements in morphology and genetic characteristics of
      pancreatic tumors with ductal phenotype is presented. Problems of intraductal
      pancreatic neoplasia (PanIN) as precancerous process for ductal adenocarcinoma
      are considered in detail.

PMID- 16405020
TI  - [Immunohistochemical study of E-cadherin, beta-catenin and CD-44v6 expression in
      the cells of primary colon cancer and its metastases].
AB  - 129 primary colon carcinomas, 35 metastases to the lymph nodes and 92 metastases
      to the liver are studied. Reduction or complete absence of E-cadherin was more
      frequently observed in cases with liver metastases (64/ 84 - 76%) than in
      patients without metastases (14/45 - 31%) (p = 0,014). Also, beta-catenin
      expression was more frequent in cases with metastases. These results of E
      cadherin and beta-caterin expression, changes may be considered as factors of
      unfavourable prognosis. No links between CD44v6 expression and metastases was
      found.

PMID- 16405021
TI  - [Angiomyolipoma of the kidneys].
AB  - 59 angiomyolipomas were studied: immunohistochemistry (IHC) was used in 24 cases,
      electron microscopy (EM) in 6 cases. 57 tumors had a typical structure, 2 did not
      contain fat component. Premelanosomes were found by EM in one tumor. Smooth
      muscle actin was found in all tumor cells. Involvement of lymph nodes was
      observed in 2 patients. Histogenesis of this tumor is discussed.

PMID- 16405022
TI  - [Interpretation of the notion "dysplasia/ intraepitelial neoplasia" in the
      international classification of tumors].
AB  - The review of international classification of tumors of digestive tract is
      presented: that of Padua (1998), Wien (1998, 2002), WHO (2000). Principal
      definitions are considered, the content of terms "dysplastic" and "neoplasia" is
      analysed. The attempt to systematize the description of morphological picture of
      neoplasia (adenoma/dysplasia) of low and high degree and difference of uncertain
      neoplastic (dysplasia) from true neoplastic changes. Principles of clinical
      interpretation of biopsies are presented.

PMID- 16405023
TI  - [Results of the activity of pathoanatomical service in Kuzbass after its
      reorganization].
AB  - A new structure of the pathology service in the Kemerovo region which includes
      Kuznetsk area and its activity is considered.

PMID- 16405024
TI  - [Sepsis: state of the art, diagnosis and disputable problems of classification].
AB  - Sepsis is an infection without specific features but with a high variety of
      clinical manifestations, this explaining various theories and opinion on this
      problem. Main provoker of this disease is microorganisms of the strepto
      staphyllococ group producing septicopyemia. Principal morphological criterion of
      generalization is metastatic purulent focus. Disease produced by gram = negative
      bacteria is a type of the bacterial (endotoxin) shock and a main morphological
      criterion of an infection generalization is development of DBC-syndrome with
      necrosis and hemorrhages in the hypophysis-adrenal system. A separate nosological
      unit is a subacute septic endocarditis- immunocomplex, by its pathogenesis,
      disease which is necessary to differentiate with acute bacterial endocarditis in
      septicopiemia.

PMID- 16405025
TI  - [Antiamnesic activity of nerve growth factor adsorbed on poly(butyl)
      cyanoacrylate nanoparticles coated with polysorbate-80].
AB  - The antiamnesic activity of nerve growth factor (NGF) in various medicinal forms
      [aqueous NGF solution with and without polysorbate-80 (PS-80) additives, NGF
      adsorbed on poly(butyl) cyanoacrylate (PBCA) nanoparticles with and without PS-80
      coating] has been studied in rats with model amnesia induced by scopolamine (2
      mg/kg, s.c.). The antiamnesic activity was evaluated by the ability of
      subsequently introduced drugs (5 microg NGF per animal, i.p.) to inhibit the
      amnesic action of scopolamine as manifested by retrieval of the passive avoidance
      reflex (PAR) learned using the Lafayette Instruments USP system 30 min after drug
      injection. The PAR memory trace was evaluated as an increase in the latent time
      before visiting the dark compartment 24 h after drug injection. In the untreated
      amnesia control group, the scopolamine amnesia was manifested by the absence of
      any increase in the PAR latent time. In the form of an aqueous solution, NGF did
      not inhibit the scopolamine-induced amnesia. NGF adsorbed on uncoated PBCA and in
      the form of solution with PS-80 produced an antiamnesic action manifested by a
      reliable increase in the PAR latent time as compared to that in the untreated
      control group. NGF adsorbed on PBCA nanoparticles coated with PS-80 not only
      exhibited a significant antiamnesic effect, but even stimulated the cognitive
      function and increased the PAR latent time above the value in the learned control
      group.

PMID- 16405026
TI  - [Antihypoxant and antiamnesic effects of calcium ketopantoylaminobutyrate].
AB  - Experimental investigation of calcium ketopantoylaminobutyrate (Ca-KPAB), a new
      drug with a structure close to that of pantogam, showed that Ca-KPAB exhibits a
      pronounced antihypoxant effect on the normobaric and histotoxic hypoxia models.
      The new drug also produced a more pronounced antiamnesic action as compared to
      that of pantogam. A significant decrease in the effective drug dose in the case
      of Ca-KPAB is explained by its ability to readily bypass the blood - brain
      barrier.

PMID- 16405027
TI  - [Neuropharmacological study of the joint action of verapamil and olanzapine on
      the content of neurotransmitters in Wistar rat brain structures].
AB  - The effects of jointly administered olanzapine and verapamil on the level of
      neurotransmitters and their metabolites in Wistar rat brain structures have been
      studied. Verapamil (i) produces a statistically significant decrease in dopamine
      and serotonin turnover increased by olanzapine injections and (ii) increases the
      norepinephrine content in all the brain structures studied.

PMID- 16405028
TI  - [The new tripeptoid neurotensin analog dilept selectively affects dopamine
      turnover in nucleus accumbens and hypothalamus].
AB  - The effects of dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) - a new
      peptidomimetic of neurotensine - on the level of monoamines and their main
      metabolites in four functionally important brain structures has been studied upon
      single and subchronic administration in intact rats and in those pretreated with
      the NMDA receptor blocker ketamine. Repeated administration of dilept favors the
      accumulation of DOPAC and accelerates the dopamine (DA) turnover in nucleus
      accumbens, as manifested by an increase in the DOPAC/DA ratio. The opposite
      effect (decrease in the DOPAC/DA ratio) was observed in the hypothalamus, where
      the subchronic treatment with dilept completely inhibited the activating action
      of ketamine on the DA turnover. The selective influence of dilept on the
      dopaminergic system activity in nucleus accumbens (but not in striatum), together
      with the previously obtained behavioral data, suggest that dilept is a new
      atypical neuroleptic producing no extrapyramidal side effects.

PMID- 16405029
TI  - [The effect of stimulation of cardiac delta1-opioid receptors on the resistance
      of isolated heart to the action of ischemia and reperfusion].
AB  - Preliminary stimulation of cardiac delta1-opioid receptors by DPDPE addition at a
      concentration of 0.1 mg/liter to the perfusion solution decreased the incidence
      of reperfusion arrhythmias and the reperfusive destruction of cardiac cells. At
      the same time, the activation of cardiac delta1-opioid receptors resulted in a
      decrease in myocardial contractility both in the pre-ischemic period and upon
      restoration of the coronary flow. Pretreatment with naltriondole (a delta
      receptor antagonist) or with cyclopiazonic acid (a specific inhibitor of Ca2+
      uptake in sarcoplasmic reticulum) completely abolished the antiarrhythmic,
      cardioprotective, and inotropic effects of DPDPE. It is suggested that the
      antiarrhythmic, cardioprotective, and inotropic effects of DPDPE is related to
      the cardiac delta1-opioid receptor activation and Ca2+ transport alteration on
      the level of sarcoplasmic reticulum.

PMID- 16405030
TI  - [Comparative study of the antiarrhythmic activity of mu- and delta-opioid
      receptor agonists during acute cardiac ischemia and reperfusion models in rats].
AB  - It has been established that pretreatment with the selective mu-opioid receptor
      (OR) agonist DALDA (0.1 mg/kg, i.v.) or the selective delta1-OR agonists DPDPE
      (0.09 mg/kg) and/or (-)-TAN-67 (0.08 mg/kg) has no effect on the incidence of
      ventricular arrhythmias induced by a 10-min coronary artery occlusion and a 10
      min reperfusion in ketamine-anesthetized rats. In contrast, the pretreatment with
      the selective delta2-OR agonist deltorphin II (0.12 mg/kg) and the proposed
      delta2-OR agonists deltorphin D (0.3 mg/kg) and/or dermorphin H (0.23 mg/kg)
      increases cardiac resistance to the arrhythmogenic action of acute ischemia and
      reperfusion. Administration of the mixed mu- and delta-OR agonist dalargin (0.12
      mg/kg) 15 min before the coronary artery ligation abolished only the reperfusive
      ventricular fibrillation. It is concluded that peptidergic stimulation of delta2
      ORs can be used as a new means of increasing cardiac tolerance to the
      arrhythmogenic effects of acute ischemia and reperfusion.

PMID- 16405031
TI  - [Effects of lithium hydroxybutyrate and vagotomy on respiratory arrest caused by
      systemic serotonin administration in rats].
AB  - The role of gamma-hydroxybutyric acid (GHBA) and gamma-aminobutyric acid (GABA)
      in the mechanisms of respiratory arrest after systemic serotonin administration
      has been studied in anaesthetized outbred male rats. Under normal conditions,
      serotonin (5-HT) administration (20 - 60 microg/kg, i.v.) leads to specific
      changes in the respiratory pattern, whereby a short (approximately 5 sec)
      increase in the respiratory rate is followed by a longer (up to approximately 20
      sec) respiratory arrest. Pretreatment with Li-GHBA salt (750 mg/kg, i.v.) did not
      significantly change the first stage of the respiratory response to serotonin
      administration, but excluded or significantly reduced the stage of respiratory
      arrest. The effect of bilateral vagotomy on the respiratory pattern upon
      serotonin administration was very similar to the action of GHBA. It is suggested
      that GHBA as a neuromodulator probably participates in the mechanisms of
      respiratory control after serotonin administration.

PMID- 16405033
TI  - [The influence of aminostigmine on the parameters of nonspecific resistance and
      immune system of the organism upon acute poisoning of benzyl 3-quinuclidylate].
AB  - The results of experiments on outbred rats weighing 180 -240 g showed that the
      acute poisoning with benzyl 3-quinuclidylate decreases the parameters of
      nonspecific resistance of the organism, reduces the antibody production mainly to
      T-dependent antigens (sheep red blood cells), decreases the activity of natural
      killers and the antibody-dependent cell-mediated cytotoxicity, and suppresses the
      formation of delayed-type hypersensitivity. Aminostigmine partly inhibits the
      immunotoxicity benzyl 3-quinuclidylate.

PMID- 16405032
TI  - [The effect of colchicine on the periodicity of the spontaneous and induced
      respiratory burst of granulocytes and monocytes during familial Mediterranean
      fever].
AB  - The influence of colchicine on the spontaneous and chemotaxis-, protein kinase C
      , and phagocytosis-induced respiratory burst of neutrophils and monocytes in the
      peripheral blood of patients with familial Mediterranean fever (FMF) has been
      studied. The transient activation of neutrophils and monocytes on the level of a
      single cell has been monitored by means of flow cytofluorimetry. It is shown that
      colchicine blocks the induction of chemotaxis-, phagocytosis-, and proteinkinase
      C-dependent respiratory burst in vitro, as well as the increased pro-oxidant
      transient activation of neutrophils and monocytes of FMF patients, both in the
      period of remission and during the FMF attack. Colchicine stimulates the
      intensity of the spontaneous respiratory burst of neutrophils and monocytes in
      patients in the course of remission and during the FMF attack. At the same time,
      the drug effectively suppresses the periodicity of the multidirectional transient
      activation of the respiratory burst of effector cells during FMF.

PMID- 16405034
TI  - [The main pharmacokinetic parameters of p-tyrosol upon intravenous injection in
      rats].
AB  - The main pharmacokinetic parameters ofp-tyrosol upon intravenous injection have
      been experimentally studied in rats. The drug concentration in the blood was
      determined by means of spectrofluorimetry. It is established thatp-tyrosol
      rapidly penetrates into organs with high blood supply. The drug is rapidly
      eliminated from rat organism, with T1/2 approximately 70 min.

PMID- 16405035
TI  - [The neuroprotector effect of a new taurine derivative on a model of compression
      spinal cord trauma in rats].
AB  - The neuroprotector effect of a new taurine derivative, 2-(1-phenylethyl)
      aminoethanesulfonyl-2-propylamide hydrochloride, has been studied in rats with
      model compression spinal cord trauma. The drug favored restoration of the motor
      function of posterior extremities in rats with the model spinal cord trauma and
      significantly decreased the lethality in test animals. The taurine derivative
      normalized the energy metabolism, lipid peroxidation and antioxidant system in
      animals with spinal cord trauma. The neuroprotector effect of the new taurine
      derivative significantly exceeds the action of cerebrolysine.

PMID- 16405036
TI  - [The effect of betulonic acid and its alanine amide derivatives on rat liver
      parenchyma repair during postcytostatic period].
AB  - The effects of betulonic acid, its p-alanine amide derivative, and p-alanine
      amide derivative of betulonic acid methyl ether on the histologic structure of
      rat liver have been studied on the model of experimental polychemotherapy in
      rats. These agents significantly decrease the dystrophic and cytolytic damage of
      hepatocytes and increase the repair processes in liver parenchyma.

PMID- 16405037
TI  - [The effect of erythropoetin on doxorubicin-induced oxidative stress in rat
      kidney].
AB  - The early nephrotoxicity manifestations (oxidative stress) caused by a single
      administration of doxorubicin in rats and the therapeutic effect of
      erythropoietin have been studied. The introduction of doxorubicin leads to a
      decrease in the concentration of glutathione and the activity of glutathione
      reductase in rat kidneys, which is indicative of the development of oxidative
      stress. Erythropoietin restores glutathione content on the normal level. The
      pretreatment with erythropoietin reduces the doxorubicin induced damage in rat
      kidneys.

PMID- 16405038
TI  - [Computer software for data acquisition during behavioral tests].
AB  - A special program package has been developed for input the results of visual
      monitoring of the behavior of animals during the Porsolt (forced swim) test, open
      field test, elevated cross labyrinth test, and passive avoidance reflex test into
      a personal computer (PC) for the subsequent data processing. According to the
      adopted procedure, all behavioral events are registered by a researcher using the
      corresponding keys on the PC keyboard. Then, the program calculates the mean
      values and their standard deviations and presents the results of data processing
      in the form of tables and graphs on display. The data can be also printed and
      stored on disk. The disk files can be imported into other programs (Microsoft
      Office, Microsoft Excel, etc.) for further processing. The proposed software
      facilitates the procedure and increases the accuracy of experiments. The programs
      were successfully verified in the laboratories of the Zakusov Institute of
      Pharmacology.

PMID- 16405039
TI  - [Functional changes of myocardial adrenoreceptors in patients with chronic
      cardiac insufficiency].

PMID- 16405040
TI  - [Modern approaches to pharmacotherapy of recidivating herpes infection].

PMID- 16405041
TI  - [Forensic-medical assessment of pathomorphological changes in the myocardium in
      blunt chest trauma with an isolated heart contusion].
AB  - A total of 37 autopsy cases were divided into two groups. Group 1 consisted of 17
      victims who had died of closed blunt trauma of the chest with isolated heart
      contusion made by fists, feet in shoes. Group 2 (control) consisted of 20 cases
      of sudden death of ischemic heart disease because of atherosclerotic
      cardiosclerosis. Fragments of the heart containing endocardium were studied on
      the microscope JEIL-SM200 (Japan). Endocardium pathomorphology was represented by
      relief changes of the endocardium, structural arrangement of separate groups of
      muscular fibers above the endocardium surface, hemorrhages and blood clots,
      endotheliocyte desquamation, prelacerations, lacerations and destruction of the
      endocardium.

PMID- 16405042
TI  - [Dielectric parameters of the tissues as additional criteria of postmortem period
      duration in medical examination of dismembered corpses].
AB  - We studied dielectric indices of soft tissues from the parts of the dismembered
      corpses (skin, fragments of head, trunk extremities muscles) in terms of
      postmortem period duration. True (epsilon/) and false (epsilon//) parts of
      dielectric permeability at 10 cm wave length were determined. We obtained the
      curves characterizing changes in tissue dielectric parameters for 30 days after
      death. Thus, biophysical parameters of dismembered coupse fragments allow precise
      dating of death.

PMID- 16405043
TI  - [Determination of death mechanisms in forensic-medical examination of a corpse].
AB  - Applied aspects of multivalued and modal logics served the basis for the proposed
      algorithm of tanatological analysis of autopsy material including formalization
      of semiquantitative data on changes in vital organs with further conversion of
      the estimated tanatogenetic coefficients in the form of probability suggestions
      leading to the conclusion about the kind and speed of tanatogenesis. The method
      is illustrated by cases from expert practice.

PMID- 16405044
TI  - [Assessment of unfavorable outcomes of dental care provoked by the patient].
AB  - Some causes of ineffective dental care because of the patient's negligence were
      analyzed. In 16 cases the patients ignored recommendations of the dentist and
      missed visits to the doctor. As a result, the patients developed complications
      leading to esthetic dissatisfaction, prolonged treatment, repeated prosthetic
      management.

PMID- 16405046
TI  - [A complex forensic-medical molecular-genetic examination of the victims of
      terroristic bombing in Moscow underground].
AB  - The authors emphasize the need in coordination when conducting expert
      examinations in investigation of accidents with a great number of victims.
      Coordination is of special importance for combined application of molecular
      genetic technologies and standard forensic medical investigations. The experience
      in experts cooperation in investigation of terroristic bombing in Moscow
      underground on February 6, 2004, according to algorithm of combined use of
      conventional forensic medical methods and innovating techniques of molecular
      genetic identification for personal identification of dead bodies in accidents
      with a great number of victims is demonstrated.

PMID- 16405045
TI  - [Identification problems in emergencies with human victims].
AB  - The problems and errors in personal identifications in rescue work after
      accidents with a large number of human victims are considered. The order of
      actions of forensic medical experts in personal identification in emergency
      situation is proposed.

PMID- 16405047
TI  - [Criteria of personal identification by the hyoid bone].
AB  - We studied 16 sizes of the hyoid bone (HB) from 158 corpses of known gender,
      Russians, who had died at the age over 15 years by the K. Miller et al program
      (1998) and 205 back projection electroroentgenograms of the neck of patients of
      the traumatological hospital in the town of Kirov. HB skeletization was made by
      the enzymatic drug enzyme. SPSS package and multidimentional statistics
      (regression and discriminant analyses) were used for data processing. It was
      established that HB is an informative object of forensic medical personal
      identification allowing determination of the body length and gender as well as
      anatomical, x-ray and osteometric individual features. Precision of human body
      length diagnosis by HB is 6.71-7.26 cm. Therefore, this method should be used in
      combination with the diagnosis by long tubular bones. Diagnosis of human gender
      by osteometric signs of HB based on one-dimentional discriminant analysis is
      feasible in 80-85%, based on canonical discriminant analysis--in 91.1% cases. The
      method of anatomic, osteometric and roentgenological assessment of HB
      individuality can be used in personal identification by intravital x-ray of
      cervical organs and in traumatic defects of HB. The methods may be applied in
      forensic medical practice in expert examination of body fragments or isolated
      bone fragments.

PMID- 16405048
TI  - [New approaches to investigation of bone tissue according to the isoserological
      system ABO].
AB  - To detect ABO antigens in human bone tissue, we offer to treat standard
      isohemagglutinating and heteroimmune sera with anti-A and anti-B raising their
      specificity; use of high-avid immunoreagents produced by novel technique;
      different modifications of absorption-elution reactions providing significant
      results.

PMID- 16405049
TI  - [Injuries made by shooting from the self-defence gun--a traumatic gun Strazhnik].

PMID- 16405050
TI  - [Forensic medical assessment of bone fractures].

PMID- 16405051
TI  - Chemically dependent employees and the ADA in the medical profession: does
      patient safety exempt hospital employers from compliance under the direct threat
      and/or the business necessity exceptions?

PMID- 16405052
TI  - [Role of high-frequency duplex scanning in the differential diagnosis of uveal
      melanomas and solitary choroidal hemangiomas].
AB  - The present paper presents the results of a study of hemodynamic features in 83
      patients with intraocular tumors (74 uveal melanomas and 9 solitary choroidal
      hemangiomas), by applying high-frequency duplex scanning with color Doppler
      coding and Doppler spectral analysis of flows. The tumors in question are shown
      to differ in the qualitative and quantitative indicators of blood flow, which can
      be successfully used in the complex differential diagnosis and in the adjustment
      of management policy in the patients of this category.

PMID- 16405053
TI  - [Magnetic resonance imaging of the orbital portion of the optic nerve at
      different stages of papilledema].
AB  - High-resolution magnetic resonance image makes it possible to examine the
      radiological anatomy of the orbital portion of the optic nerve in patients with
      papilledema. The longitudinal diameters of the orbital portion of the optic nerve
      and its subarachnoidal space were measured on coronal images just behind the
      eyeball, in the middle of the latter and the orbital apex, and at the orbital
      apex in 10 healthy volunteers and 20 patients with papilledema. In patients with
      papilledema, the diameter of the subarachnoidal space of the optic nerve was
      increased as compared with that in the control group. In its moderate form, that
      of the optic nerve was significantly increased as compared to the control group.
      In patients with severe papilledema and secondary atrophy, the diameter of the
      optic nerve just behind the eyeball was significantly less than that in patients
      with moderate papilledema. It may be suggested that elevated intracranial
      pressure leads to the dilated subarachnoidal space of the optic nerve. The
      clinical and X-ray signs of atrophy of the optic nerve are detectable in patients
      with severe papilledema and secondary atrophy.

PMID- 16405054
TI  - [Computed tomography in diagnosing and determining treatment policy in patients
      with posttraumatic pathology of the eye and orbit].
AB  - The paper analyzes the diagnostic value of computed tomography (CT) in
      posttraumatic lesion of the eye socket, ball, and appendage and identifies the
      basic groups of patients in whom CT is an essential study. In 2004, the
      Department of Traumatology, Reconstructive Surgery, and Eye Prosthesis, Helmholtz
      Research Institute of Eye Diseases, performed CT in 323 patients (18.2% of the
      inpatients and 3.4% of the outpatients). Analyzing all CT images identified the
      basic groups of patients in whom this study was essential. The CT scans
      characterizing examples from each group of patients are given. The studies could
      extend indications in patients with posttraumatic lesion of the eye and orbital
      area for CT. The latter is an important and essential study in patients with
      traumatic pathology of the eye with multiple and hard-to-reach foreign bodies and
      with trauma of the soft and osseous structures of the orbit, which makes it
      possible to determine not only the possibility, but also pattern and scope of a
      surgical intervention and to assess its long-term result.

PMID- 16405055
TI  - [Local microcirculation in persons with primary pterygium, as evidenced by
      fluorescein-angiographic studies].
AB  - Fluorescence angiography was used to study local microcirculation in 20 patients
      (9 females and 11 males) aged 18 to 48 years who had primary pterygium. All
      pterygiums were divided into unprogressive (10 patients, 10 eyes) and progressive
      (10 patients, 10 eyes). The revealed pattern of the microangioarchitectonics of
      pterygium suggests that there is an independent isolated microvascular system
      that comprises a system of posterior conjunctival vessels, relatively large
      arterial trunks, and a developed newly formed vasculature. Unprogressive
      pterygium is characterized by a slightly developed neovasculature in the tissue
      of pterygium, in its head in particular, while the progressive form is marked by
      a rich neovasculature with pronounced extravasal fluorescence.

PMID- 16405056
TI  - [To the biometric evaluation in ophthalmoplasty].
AB  - The paper gives the preliminary results of an analysis of the metric
      characteristics of images in 40 patients with the anomalous outline of the lid
      slit of varying genesis, by applying an original computer program. The program is
      based on the principle of automatically finding the line of the true symmetry of
      the face, its paired fixed points, and the orientation of an image. Computer
      aided estimation of the shape and width of the lid slit, the parameters of the
      lids along the conventional lines shows that the measurements are of high
      accuracy (0.1 mm for linear values and 0.1 for angular values). The paper
      analyzes the effect of modified resection of the superior tarsal muscle. In a
      patient with aponeurotic ptosis, the uplift of the upper lid was 4.1 mm (1.9 mm
      higher than that obtained by a pharmacological test). In the author's opinion,
      the proposed procedure makes it possible to solve the problems associated with
      the processing, storage, and transmission of images and with the assessment of
      relationships of the structures of the appendage of the eye.

PMID- 16405057
TI  - [Long-term results of xenoscleroplasty of the posterior pole of the eyeball in
      the treatment of patients with progressive myopia].
AB  - The study deals with the development of an effective, atraumatic and easy-to-use
      treatment for patients with progressive myopia, by using a discoid xenograft. The
      treatment involves implantation of a discoid xenograft to the episclera of the
      posterior pole of the eye. The xenograft is a white disk prepared from the
      treated bovine pericardium and it has 2 mm in thickness and a diameter of 13 mm.
      Clinical studies were performed in 89 patients (161 eyes) operated on by the
      proposed procedure, by evaluating the stabilized progression of myopia 4 years
      later. In the late period of a follow-up, the stabilization effect was 88.3 to
      92.6% in relation to the degree of myopia. There was evidence for increases in
      the thickness of the sclera (and its acoustic density) on the posterior pole of
      the eye, for improved regional hemodynamics and better electrophysiological
      functions of the retina in the postoperative period. Xenoscleroplasty of the
      posterior pole of the eye with a bovine pericardial xenograft is an easy-to-use,
      pathogenetically oriented, highly effective, and safe treatment in patients with
      progressive myopia.

PMID- 16405058
TI  - [Use of physiological reparation regulators in glaucoma surgery: a
      clinicoimmunological study].
AB  - The paper presents the comparative results of clinical and immunological studies
      dealing with the use of the physiological reparation regulators (the human
      amniotic membrane and systemic enzyme therapy) and the antimetabolite 5
      fluorouracil (5-FU) to prevent excessive ocular tissue scarring. The clinical
      observations have demonstrated the high efficiency of the proposed methods for
      the physiological regulation of reparative processes as compared with the use of
      5-FU, which manifested as a more marked normalization ofophthalmotonus and fewer
      numbers of postoperative complications. The investigation of the study of
      proliferation-activating cytokine (TGF-beta1) and antiprolerative cytokine (IFN
      gamma) has demonstrated the immunomodulating properties of the physiological
      reparation regulators used in the present study.

PMID- 16405059
TI  - [Impact of the quality of surgical treatment of subconjunctival ruptures of the
      sclera on their outcome].
AB  - The paper deals with the analysis of the outcome of severe eye contusion in
      scleral ruptures that are subject to none or inadequate debridement. In 2004, a
      group of 85 patients undergone enucleation due to severe posttraumatic changes
      was examined to analyze the outcomes of misdiagnosis of ruptures of the scleral
      capsule of the eye in its contusions and penetrating wounds. Examination of the
      eyeball after its removal revealed different defects of the optic scleral capsule
      in 6 (8.2%) cases of the 85 patients undergone enucleation. Each case pointing to
      the undiagnosed pathology of the eye during primary debridement and surgical
      treatment of these patients or to the partial debridement of scleral wounds is
      noteworthy. It should be noted that a primary care involving debridement was
      delivered to virtually all patients in different ophthalmological facilities. The
      paper gives a detailed account of each case, by describing its history data, the
      state of the eye, the performed studies and operation, and presents photos
      demonstrating each case. In eye contusion, it is necessary to adequately evaluate
      its severity and to reveal the whole complex of injuries and also to pay
      attention to the quality of debridement of wounds since adequate containment of a
      wound of the eye and adaptation of its edges can preserve the eye as an organ in
      most given cases.

PMID- 16405060
TI  - [Impaired antiendotoxin immunity in patients with diabetic retinopathy and type 2
      diabetes mellitus].
AB  - Solid-phase enzyme immunoassay was used to study the serum levels of the
      antiendoxin IgA, IgM, IgG antibodies and total immunoglobulins of classes A, M,
      and G in 62 patients (122 eyes) with type 2 diabetes mellitus at different stages
      of diabetic retinopathy. Patients with diabetic retinopathy concurrent with type
      2 diabetes mellitus were found to have a significant imbalance of antiendotoxin
      immunity. The highest level of anti-lipopolysaccharide (LPS)-IgA was detected in
      patients with nonproliferative diabetic retinopathy that exhibited macular edema,
      single or multiple aneurysms, hemorrhages, portions of solid lipid exudate and
      preproliferative diabetic retinopathy, in addition to vascular changes. Much
      lower levels of anti-LPS-IgA were found in nonproliferative retinopathy in which
      only retinal vascular changes and in proliferative diabetic retinopathy were
      noted. The patients with proliferative diabetic retinopathy complicated by
      neovascular glaucoma were ascertained to have the lowest levels of antiendotoxin
      antibodies of all the classes. As compared with the control group, the patients
      of all groups had the decreased levels of anti-LPS-IgM. The paper presents the
      results of a correlation analysis of the relationship of the parameters of
      antiendotoxin immunity to the levels of total immunoglobulins.

PMID- 16405061
TI  - [Theoretical rationale for corneal curvature changes after formation of a corneal
      flap at intrastromal keratectomy].
AB  - Mathematical simulation was used to study possible changes in the corneal
      curvature while making a corneal flap of varying thickness. It has been shown
      that flap formation can result in decreased corneal refraction in the central
      zone, the degree of which depends on the thickness of a section. The above
      changes may be marked if the cornea diminishes its strength properties (for
      example, in cicatricial changes).

PMID- 16405062
TI  - [Focusing strength and a subjective method for determining refraction].
AB  - Three hundred and seventy-four eyes were examined by a subjective method, by
      using trial lenses in natural accommodation. This yielded the following
      distribution of clinical refraction: hypermetropia (43.6%), emmetropia (30.8%),
      myopia (12.8%), and astigmatism (12.8%). The classical subjective method of
      refractometry is based on the schematic eye having no focusing strength. The
      currently available data by a number of authors show that the focusing strength
      of more than 0.5 diopters is typical of the human eye, which affects the results
      of refractometry. When the collecting glass +0.25 D or +0.5 D is applied, the eye
      with a visual acuity of 1.0 or more retains the level of vision due to the
      holding the focusing strength across the retina rather than the accommodation
      strength. By taking in account the correction, the distribution in the study
      group was as follows: emmetropia (73.0%), myopia (12.8%), astigmatism (12.8%),
      and hypermetropia (1.4%).

PMID- 16405063
TI  - [Results of surgical treatment for cataract with implantation of intraocular
      lenses in children with insulin-dependent diabetes mellitus].
AB  - Primary implantation of intraocular lenses (IOLs) was made in 9 children (16
      eyes) after removal of cataract; secondary implantation was performed in 2
      children (4 eyes) 3 and 4 years after diabetic cataract aspiration. After
      surgery, 4, 4, and 3 children were followed up 1, 2, and 3 years, respectively.
      Thirteen cases of secondary cataract were observed after primary implantation (16
      eyes); secondary cataract was recorded in 100% of cases after implantation of
      polymethyl methaacrylate IOLs and hydrophilic "Centrflex" lenses and only in
      57.1% after implantation of hydrophobic "Acrysof" lenses. The visual acuity was
      0.48 +/- 0.14 after removal of secondary cataract and 0.88 +/- 0.11 after laser
      discission. Laser invention did not lead to the progression or occurrence of
      diabetic retinopathy (DR) in the late periods of a follow-up. Cataract removal
      with IOL implantation in children with insulin-dependent diabetes (IDD) yields
      high functional results. The postoperative follow-up did not demonstrate a
      significant increase in the severity and incidence of DR, which seems to be
      associated both with a good postoperative IDD compensation and preventive
      treatment. The use of the hydrophobic flexible lenses is more optimal to prevent
      the development of secondary cataract.

PMID- 16405064
TI  - [Late changes in a recipient's tissues after implantation of synthetic
      hydroxyapatite of varying density: an experimental morphological study].
AB  - The synthetic hydroxyapatite made in Russia was applied as an insert-implant to 4
      rabbits (6 eyes, 6 eviscerations). These included 2 implants having a porosity of
      40% and a pore size of 0.03-1.5 microm and 2 with a porosity of 63% and a pore
      size of 0.05-3.0 microm. The hydroxyapatite that is made in Russian and that has
      preferably a porosity of 40% and a pore size of 0.03-1.5 microm can be
      successfully used to make a locomotor stump after removal of the eyeball. The
      hydroxyapatite having these parameters more rapidly intergrows around the
      periphery with fibrovascular tissue and its vascular components mainly reduce by
      month 8. Our data suggest that the synthetic hydroxyapatite made in Russia may be
      used in ophthalmological care.

PMID- 16405065
TI  - [Examination of the local antioxidative system of the eye in experimental corneal
      burn injury and the prospects for pharmacological correction of its parameters].
AB  - The present paper deals with the study of the efficiency of oral use of the
      antioxidative drug Immugen (a complex of alpha-tocopherol, oubichinone, selenium
      aspartate, methionine, and soyabean phospholipids) on a rabbit model of severe
      alkaline-induced corneal burn. The investigations have indicated that addition of
      Immugen to the rabbit feed exerts a significant positive effect on the parameters
      of the local antioxidative system of the eye and causes an increase in the
      activity of superoxide dismutase and catalase, and, on day 14, in antioxidative
      activity. The early experimental periods were marked by a slight rise in the
      frequency of deep corneal ulcerations. Moreover, the long-term clinical effect of
      use of Immugen appears as a significant increase in the area of the transparency
      preserving affected cornea. The findings suggest that the antioxidants can show
      their optimal effect in the complex therapy for burn processes, including the use
      of proteinase inhibitors.

PMID- 16405066
TI  - [Experimental study of the efficiency of use of sodium hypochlorite in the
      complex treatment of purulent keratitis].
AB  - The experiment has provided evidence for the safe use of 0.1% aqueous sodium
      hypochlorite for ocular tissues and for its therapeutic efficacy in purulent
      keratitis. The therapeutic effect is achieved by accelerating the lysis of
      neurotic tissues, by suppressing the pathogenic microflora, by alleviating an
      inflammatory reaction, by stimulating epithelization and reparative regeneration,
      by activating the phagocytic properties of neutrophilic leukocytes by 1.8-times,
      by increasing their functional reserves by 1.3 times as compared to the similar
      parameters observed in the use of conventional treatments.

PMID- 16405067
TI  - [A case of medical and social rehabilitation of a patient after severe
      penetrating wound of both eyes].

PMID- 16405068
TI  - [Cataract surgery in patients with high myopia].

PMID- 16405069
TI  - [Value of nitric oxide and peroxynitrite in the pathogenesis of uveitis].

PMID- 16405070
TI  - [Biologically active substances and their involvement in the pathogenesis of
      proliferative vitreoretinopathy].

PMID- 16405071
TI  - A novel method of cryopreservation of rat and human hepatocytes by using
      encapsulation technique and possible use for cell transplantation.
AB  - Encapsulated hepatocyte transplantation is a promising approach to cell
      transplantation without immunosuppression as an alternative to whole organ liver
      transplantation. However, the shortage of donor cells for hepatocyte
      transplantation has not been resolved, and at this critical point, it seems
      necessary to establish a method of hepatocyte cryopreservation to allow clinical
      application of hepatocyte transplantation and the development of a bioartificial
      liver system in the near future. In this study we demonstrated that cryopreserved
      microencapsulated rat and human hepatocytes can retain their hepatic function and
      that cryopreserved microencapsulated human hepatocytes transplanted into rat
      spleen remain viable without immunosuppression. Rat and human hepatocytes were
      isolated by a collagenase digestion method, and they were microencapsulated with
      poly-L-lysine. The microencapsulated rat hepatocytes were transferred to culture
      medium (DMEM containing 10% FBS and 10% DMSO) and immediately frozen in liquid
      nitrogen. A warm water bath (37 degrees C) was used to thaw the microencapsulated
      hepatocytes. Hepatic function, drug metabolism, and cell morphology were assessed
      after 90 days of cryopreservation. After 1 week of cryopreservation,
      microencapsulated hepatocytes were cultured for up to 2 weeks to assess their
      hepatic function and morphology. The morphology of human hepatocytes was assessed
      after 30 days of cryopreservation. Cryopreserved human hepatocytes were
      transplanted into rat spleen to assess their morphology. Cryopreserved
      microencapsulated hepatocytes retained their viability and were strongly positive
      for expression of albumin, OAT2, CYP3A2, and CYP3A9. Two weeks after cultivation,
      the cryopreserved microencapsulated rat hepatocytes had retained their hepatic
      function (urea synthesis). Cryopreserved microencapsulated human hepatocytes also
      mainly survived and retained their hepatic function for at least 30 days after
      cryopreservation. Moreover, entrapped cryopreserved human hepatocytes also
      survived and expressed albumin in rat spleen after transplantation. We
      demonstrated a novel method of long-term cryopreservation of rat and human
      hepatocytes by using an encapsulation technique, with retention of biological
      activity and excellent survival of the cryopreserved microencapsulated human
      hepatocytes transplanted into rat spleen. We believe that this novel approach to
      hepatocytes cryopreservation provides a new direction in encapsulated cell
      therapy with the goal of clinical application in the near future.

PMID- 16405072
TI  - Stability and repeat regeneration potential of the engineered liver tissues under
      the kidney capsule in mice.
AB  - Liver tissue engineering using hepatocyte transplantation has been proposed as a
      therapeutic alternative to liver transplantation toward several liver diseases.
      We have previously reported that stable liver tissue with the potential for liver
      regeneration can be engineered at extrahepatic sites by transplanting mature
      hepatocytes into an extracellular matrix. The present study was aimed at
      assessing the liver tissue persistence after induced regeneration by hepatectomy
      and repeat regeneration potential induced by repeat hepatectomy. Mouse isolated
      hepatocytes mixed in EHS extracellular matrix gel were transplanted under both
      kidney capsules of isogenic mice. The hepatocyte survival persisted for over 25
      weeks. In some of the mice, we confirmed that the grafted hepatocytes developed a
      thin layer of liver tissues under the kidney capsule, determined by specific
      characteristics of differentiated hepatocytes in cord structures between the
      capillaries. We then assessed the regenerative potential and persistence of the
      exogenous liver tissue. To induce liver regeneration, we performed a two-thirds
      hepatectomy at 70 days after hepatocyte transplantation. Three weeks after this
      procedure, the engineered liver tissues showed active regeneration, reaching
      serum marker protein levels of 261 +/- 42% of the prehepatectomy level. We found
      that the regenerated liver tissue was stably maintained for 100 days (length of
      the experiment). Repeat regeneration potential was established by performing a
      repeat hepatectomy (that had been two-thirds hepatectomized at day 70) 60 days
      after the initial hepatectomy. Again, the regenerated engineered liver tissues
      showed active regeneration as there was an approximately twofold increase in the
      serum marker protein levels. The present studies demonstrate that liver tissue,
      which was recognized as a part of the host naive liver in terms of the
      regeneration profile, could be engineered at a heterologous site that does not
      have access to the portal circulation.

PMID- 16405073
TI  - Long-term maintenance of liver-specific functions in cultured ES cell-derived
      hepatocytes with hyaluronan sponge.
AB  - This study investigated the three-dimensional culture of hepatocytes
      differentiated from mouse embryonic stem (ES) cells with a porous hyaluronan (HA)
      sponge support. Hepatocytes were immobilized within the pores of the support.
      Spheroids could be observed within the support, each containing between 20 and 50
      hepatocytes. To examine the liver-specific functions of the hepatocytes in the
      culture, the levels of albumin secreted into the medium were analyzed. The
      secretion of albumin was stable over the course of 32 days, longer than that in
      both conventional monolayer and collagen sponge cultures. To elucidate further
      the liver-specific functions of hepatocytes embedded in the HA sponge, metabolic
      activities of the hepatocytes were examined for their ability to eliminate
      ammonia from culture media and the synthesis of urea nitrogen. While rates of
      ammonia removal and urea nitrogen synthesis were similar to those in both
      conventional monolayer and in collagen sponge cultures, these functions were
      maintained for longer duration in cells embedded in the HA sponge. These results
      demonstrate that the porous HA sponge is an effective support for the in vitro
      culture of ES-derived hepatocytes used for both basic and applied studies for
      cell transplantation.

PMID- 16405074
TI  - PDX-1 protein is internalized by lipid raft-dependent macropinocytosis.
AB  - PDX-1 plays a central role in regulating insulin gene transcription and
      differentiation of insulin-producing cells. It was previously reported that, due
      to its own Antennapedia-like protein transduction domain (PTD), exogenous PDX-1
      protein can permeate cells and induces insulin gene expression in pancreatic
      ducts, thought to be islet progenitor cells. These data suggest that PDX-1
      protein transduction could be a safe and valuable strategy for facilitating
      differentiation of progenitor cells into insulin-producing cells without
      requiring gene transfer technology. Here it is shown that after an initial ionic
      cell-surface interaction, PDX-1 proteins are rapidly internalized by lipid raft
      dependent macropinocytosis. HeLa cells were treated with both FITC-conjugated PDX
      1 PTD and FM 4-64, a general fluorescent marker of endocytosis. A punctate
      cytoplasmic distribution of PDX-1 PTD, which colocalized with FM 4-64, was
      observed in treated cells. Because expression of dominant-negative dynamin-1 did
      not block PDX-1 PTD uptake, PDX-1 protein transduction is independent on
      phagocytosis and clathrin- or caveolar-mediated endocytosis. Cells were
      pretreated with amiloride, a specific inhibitor of the Na+/H+ exchange required
      for macropinocytosis, or cytochalasin D, an F-actin elongation inhibitor.
      Treatment of cells with both macropinosome inhibitors resulted in the reduction
      in PDX-1 PTD transduction into vesicles, suggesting that PDX-1 PTD-mediated
      cellular entry occurs by lipid raft-mediated macropinocytosis. Taken together,
      these observations provide the mechanism of PDX-1 protein transduction and
      suggest that the protein transduction system could work for experimental and
      therapeutic strategies.

PMID- 16405075
TI  - Differentiation of adult hepatic stem-like cells into pancreatic endocrine cells.
AB  - To apply cell transplantation for treatment of diabetes mellitus, a sufficient
      number of beta-cell sources are required. In the present study, we examined
      whether an epithelial cell line obtained from normal adult rat liver, namely
      hepatic stem-like (HSL) cells, which can be converted to both hepatocytes and
      billiary epithelial cells, could be a potential beta-cell source. The growth
      speed of HSL cells was rapid and these cells were easily expanded in vitro.
      Bipotential hepatic stem cells, HSL cells, also expressed PGP9.5, which is
      expressed in neurons, beta-cells, and progenitor cells of the pancreatic
      endocrine cells as well. Sodium butyrate induced morphological changes in HSL
      cells and converted them into flattened cells with large cytoplasm. When HSL
      cells were incubated with a combination of 5 mM sodium butyrate and 1 nM
      betacellulin, most of the cells were converted into morphologically neuron-like
      cells. RT-PCR analysis revealed that a series of transcriptional factors involved
      in differentiation of pancreatic endocrine cells was induced by the treatment
      with sodium butyrate and betacellulin. mRNAs for insulin, pancreatic polypeptide,
      and somatostatin were also observed. Immunoreactive pancreatic polypeptide,
      somatostatin, and insulin were detected in sodium butyrate and betacellulin
      treated HSL cells. In conclusion, HSL cells obtained from adult normal liver also
      have the potential to differentiate into pancreatic endocrine cells in vitro. HSL
      cells may be one of the potential beta-cell sources for cell transplant therapy
      for insulin-dependent diabetes.

PMID- 16405076
TI  - In vivo PET measurements with [11C]PE2I to evaluate fetal mesencephalic
      transplantations to unilateral 6-OHDA-lesioned rats.
AB  - Positron emission tomography (PET) is a useful tool to assess and visualize
      neurotransmissions in vivo. In this study, we performed repeated PET scans with
      [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of
      the expression of dopamine (DA) transmission component after a fetal
      mesencephalic transplantation. The fetal mesencephalic cells were transplanted
      into the striatum of unilateral 6-OHDA-lesioned rats. PET scans with [11C]PE2I
      were performed to evaluate the DA transporter before and 2 and 4 weeks after the
      transplantation. Rotation behavior tests, in vitro autoradiography, measurements
      of DA contents in the striatum by high-performance liquid chromatography (HPLC),
      and tyrosine hydroxylase (TH) immunohistological examinations were performed at
      the same time points and examined for their relationship to changes in the
      dopamine transporter. The number of ipsilateral rotations induced by
      methamphetamine injections decreased. DA contents in the striatum measured with
      HPLC significantly increased. In the PET study, the binding potential of
      [11C]PE2I increased at 4 weeks. The results of the in vitro autoradiography study
      corresponded with those of the PET study. The degrees of the change in the
      binding potentials correlated with those of the numbers of rotations in the
      behavioral study and the DA contents in the striatum. In the histological
      examination, TH-positive cells with axons were observed at 2 and 4 weeks after
      the transplantation. As the dopamine transporter exists only in the axon terminal
      of DA neurons, these results suggested that PET measurements of [11C]PE2I binding
      indicated not only survival, but maturity and functioning of the transplanted
      cells. Repeated PET measurements of DA transporters are a useful tool in
      assessing the effectiveness of neural transplantations.

PMID- 16405077
TI  - Promotion of neurite outgrowth from fetal hippocampal cells by TNF-alpha receptor
      1-derived peptide.
AB  - Cytokines such as tumor necrosis factor-alpha (TNF-alpha), FasL, and TNF-related
      apoptosis-inducing ligand (TRAIL) induce apoptosis or inflammation through
      binding to their specific receptors, TNFR1, Fas, and DR5, respectively. We have
      previously reported ligand-binding and cell death-inhibiting synthetic peptides,
      which were designed based on the crystal structure of a ligand-receptor complex
      and the homology of the amino acid sequence among the death receptor family
      members. Here we show that, among these death receptor-derived peptides, the
      TNFR1-derived peptide specifically arrested cell proliferation and promoted cell
      adhesion of fetal rat (E16) hippocampal cells, and promoted neurite outgrowth
      from hippocampus-derived neurospheres cultured with the addition of the peptide
      or cultured on a peptide-coated surface. Furthermore, among these death receptor
      derived peptides, marked neurite outgrowth was observed only when the
      neurospheres were cultured on a TNFR1-derived peptide-conjugated covalently cross
      linked alginate gel. The neurites from the neurospheres positively immunostained
      with an antibody against neurofilaments. These results suggest that the TNFR1
      derived peptide promotes neuronal differentiation of the hippocampal neural stem
      cells and the TNFR1-derived peptide-conjugated covalently cross-linked alginate
      gel may be a useful material for assisting neural stem cell transplantation.

PMID- 16405078
TI  - In vitro screening of exogenous factors for human neural stem/progenitor cell
      proliferation using measurement of total ATP content in viable cells.
AB  - One of the newest and most promising methods for treating intractable neuronal
      diseases and injures is the transplantation of ex vivo-expanded human neural
      stem/progenitor cells (NSPCs). Human NSPCs are selectively expanded as free
      floating neurospheres in serum-free culture medium containing fibroblast growth
      factor 2 (FGF2) and/or epidermal growth factor (EGF); however, the culture
      conditions still need to be optimized for performance and cost before the method
      is used clinically. Here, to improve the NSPC culture method for clinical use, we
      used an ATP assay to screen the effects of various reagents on human NSPC
      proliferation. Human NSPCs responded to EGF, FGF2, and leukemia inhibitory factor
      (LIF) in a dose-dependent manner, and the minimum concentrations eliciting
      maximum effects were 10 ng/ml EGF, 10 ng/ ml FGF2, and 5 ng/ml LIF. EGF and LIF
      were stable in culture medium without NSPCs, although FGF2 was degraded. In the
      presence of human NSPCs, however, FGF2 and LIF were both degraded very rapidly,
      to below the estimated minimum concentration on day 3, but EGF remained above the
      minimum concentration for 5 days. Adding supplemental doses of each growth factor
      during the incubation promoted human NSPC proliferation. Among other supplements,
      insulin and transferrin promoted human NSPC growth, but progesterone, putrescine,
      selenite, D-glucose, and lactate were not effective and were cytotoxic at higher
      concentrations. Supplementing with conditioned medium from human NSPCs
      significantly increased human NSPC proliferation, but using a high percentage of
      the medium had a negative effect. These findings suggest that human NSPC culture
      is regulated by a balance in the culture medium between decreasing growth factor
      levels and increasing positive or negative factors derived from the NSPCs. Thus,
      in designing culture conditions for human NSPCs, it is useful to take the
      individual properties of each factor into consideration.

PMID- 16405079
TI  - Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human
      auricular chondrocytes.
AB  - Chondrocyte preparation with the safety and efficiency is the first step in
      cartilage regenerative medicine. To prepare a chondrocyte proliferation medium
      that does not contain fetal bovine serum (FBS) and that provides more than a 1000
      fold increase in cell numbers within approximately 1 month, we attempted to use
      the medium containing 5% human serum (HS), but it exerted no more than twofold
      increase in 2 weeks. To compensate for the limited proliferation ability in HS,
      we investigated the combinational effects of 12 factors [i.e., fibroblast growth
      factor (FGF)-2, insulin-like growth factor (IGF)-I, insulin, bone morphogenetic
      protein-2, parathyroid hormone, growth hormone, dexamethasone, 1alpha25-dihydroxy
      vitamin D3, L-3,3',5'-triodothyronine, interleukine-1 receptor antagonist, 17beta
      estradiol, and testosterone] on the proliferation of human auricular chondrocytes
      by analysis of variance in fractional factorial design. As a result, FGF-2,
      dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation,
      while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the
      proliferation. Actually, the chondrocytes increased 7.5-fold in number in 2 weeks
      in a medium containing 5% HS with 10 ng/ml FGF-2, while the cell number
      synergistically gained a 10-12-fold increase with 5 microg/ml insulin or 100
      ng/ml IGF-I in the same period. The proliferation effects were more enhanced at a
      concentration of 100 ng/ml for FGF-2, and especially for the combination of 100
      ng/ml FGF-2 and 5 microg/ml insulin (approximately 16-fold within 2 weeks). In
      the long-term culture with repeated passaging, this combination provided more
      than 10,000-fold within 8 weeks (i.e., passage 4). Thus, we concluded that such a
      combination of FGF-2 with insulin or IGF-I may be useful for promotion of
      auricular chondrocyte proliferation in a clinical application for cartilage
      regeneration.

PMID- 16405080
TI  - Time course evaluation of reparative cartilage with MR imaging after autologous
      chondrocyte implantation.
AB  - The aim of this study was to evaluate the qualitative change in reparative
      cartilage after autologous chondrocyte implantation (ACI). Ten knees of 10
      patients were studied. The signal intensities of reparative and normal cartilage
      were evaluated by fat-suppressed three-dimensional spoiled-gradient recalled (FS
      3D-SPGR) MR imaging. The signal intensity (SI) index (signal intensity of
      reparative cartilage divided by that of normal cartilage) was defined and the
      change in SI index was investigated. Histological and biochemical evaluation was
      done at the second look arthroscopy. The SI index was at its lowest level
      immediately after ACI and increased with time to 9 months thereafter. After 9-12
      months, the SI index settled to almost level and was maintained at that value for
      at least 2-3 years postoperatively. The average of the SI indexes after 12 months
      to the last examination was 74.2 +/- 4.6 (range 64.2-82.8), which means signal
      intensity of reparative cartilage was maintained at a value lower than that of
      normal cartilage. The total ICRS score was 11.6 +/- 2.3 points (mean +/- SD). The
      GAG concentration was 107.9 +/- 17.0 microg/mg (mean +/- SD) in normal cartilage
      and 65.9 +/- 9.4 microg/mg in reparative cartilage. The quality of reparative
      cartilage as hyaline cartilage was inferior to that of normal cartilage. In the
      present study, the time course change in the SI index indicates that the major
      maturation process of implanted chondrocytes neared completion in 9-12 months.
      Minor changes, such as matrix remodeling with reorganization of the collagen
      fibers in reparative cartilage, may continue, but an almost identical condition
      seemed to be maintained during the first 2-3 years of follow-up. SI index does
      not always reflect all properties of reparative cartilage but may be a useful
      parameter for noninvasive evaluation.

PMID- 16405082
TI  - The fetal dermal but not loose fascial mesenchymal cells possess regenerative
      activity of dermal structure.
AB  - Fetal skin possesses a regenerative activity until certain developmental stages.
      However, the origin of cells that regenerate dermis after wounding has not been
      clarified yet. In the present study we located the origin of cells that
      reconstruct fetal dermal structure by histological examination and by marking
      cells in the loose fascia. Next we evaluated the regenerative activity of fetal
      dermal mesenchymal cells by cotransplanting with fetal epidermal cells onto the
      skin defect of scid mice. We conclude that fetal dermal mesenchymal cells but not
      loose fascial cells possess regenerative activity even on the environment in scid
      mice.

PMID- 16405081
TI  - Phenotype-specific cells with proliferative potential are produced by
      polyethylene glycol-induced fusion of mouse embryonic stem cells with fetal
      cardiomyocytes.
AB  - Because cardiomyocytes lose the ability to divide upon differentiation,
      myocardial failure is assumed to be generally irreversible. For terminal cardiac
      insufficiency, the potential for regenerative treatment by stem cells, especially
      embryonic stem (ES) cells, offers hope for the future. Recent studies showed that
      stem cells fuse spontaneously with cells remaining in damaged tissues, and
      restore tissue function. To imitate spontaneous fusion in vivo, we used
      polyethylene glycol (PEG) in vitro to fuse mouse ES cells and fetal
      cardiomyocytes and analyzed the cytochemical properties of the fused cells.
      Confocal laser scanning microscopy coupled with lipophilic dye labeling of the
      living cell membranes showed that there were fused cells of ES cells and
      cardiomyocytes after PEG treatment. By flow cytometry, the fusion efficiency
      between ES cells and cardiomyocytes was estimated to be about 45% of the total
      resulting cells. When green fluorescent protein (GFP)-expressing ES cells were
      fused with cardiomyocytes, the fused cells had immunoreactivity for GFP in their
      cytoplasm and cardiac troponin I in their myofibrils. Some of these cells also
      expressed proliferating cell nuclear antigen up to 11 days after fusion, the last
      time point examined. This study shows that PEG-induced fusions of mouse ES cells
      and cardiomyocytes have the cardiomyocyte phenotype and proliferation potential.

PMID- 16405083
TI  - [Tuberculosis in the North-Western Federal Okrug (2000-2004)].
AB  - Tuberculosis is an urgent problem in the North-Western Federal Okrug of the
      Russian Federation. In the past 5 years, the tuberculosis epidemic situation in
      the okrug has remained to be of strain despite the fact that the spread of
      tuberculous infection in the North-West is less than in whole Russia. The proper
      financing of tuberculosis-controlling measures, the solution of a staff
      associated problem, and the improvement of the logistic base of a tuberculosis
      service facility are required to stabilize the tuberculosis situation.

PMID- 16405084
TI  - [Today's tuberculosis: the specific features of its pathogen, clinical picture,
      and treatment].
AB  - Clinical Mycobacterium tuberculosis (MBT) strains (their genotype, drug
      resistance, and virulence) and the characteristics of their caused processes were
      studied. More than a half the studied MBT isolates belonged to the genetic family
      Beijing. As compared with mycobacteria of individual genotypes, they showed a
      significantly higher rate of multidrug resistance, polyresistance, and a high
      virulescence and caused more common and frequently progressive pulmonary lesions
      requiring the use of large-dose isoniazid and second-line drugs and early
      surgical treatment.

PMID- 16405085
TI  - [Characterization of destructive pulmonary tuberculosis (by the results of a
      clinicomathematical analysis)].
AB  - The results of examination of 56 patients with destructive pulmonary
      tuberculosis, which involved the study of biochemical parameters characterizing
      different stages of an inflammatory process, as well as clinical and X-ray
      findings were analyzed, by applying various multivariate statistical methods.
      This approach was shown to be promising for estimating the severity of the
      process and for specifying the stage of development of an inflammatory process in
      some patients.

PMID- 16405086
TI  - [Immunological parameters and mycobacterial biological properties in infiltrative
      pulmonary tuberculosis].
AB  - Thirty-one patients with infiltrative pulmonary tuberculosis were clinically and
      immunologically examined. A relationship was found between the definite
      immunological parameters and the biological properties of mycobacteria. The
      higher viability of mycobacteria and the increase in the drug resistance have
      been shown to be associated with the decreased activity of lymphocytes and the
      suppressed production of interleukin-2, which suggests a decrease in the activity
      of type 1 T helper cells and a significant increase in the synthesis of
      tuberculosis antibodies with the lower serum concentrations of circulating immune
      complexes. This is an informative indicator of a severe specific process, as
      previously established. Moreover, the authors show certain differences in the
      changes of immunological parameters in patients with infiltrative pulmonary
      tuberculosis with varying mycobacterial properties. Thus, the results of the
      performed study make investigators pay a particular attention to the
      immunopathogenetic value of the biological properties of Mycobacterium
      tuberculosis.

PMID- 16405087
TI  - [Linear tomographic scan filtration in the diagnosis of pulmonary globular and
      cavitary masses].
AB  - To enhance the informative value and validity of X-ray study in detecting
      destructive changes in infiltrates, tuberculomas, and blocked caverns, the
      authors treated their computed tomographic scans by linear spatial filtration and
      identification of equidensite fields. In this case, after treatment of an image,
      the phase of decay in the presence of filtrates was 14.2% and increased up to
      36.1%. Cavernous processes are detectable when the scans of blocked caverns that
      are frequently taken as infiltrates are treated.

PMID- 16405088
TI  - [Outcomes of surgical treatment of patients with progressive pulmonary
      tuberculosis an concomitant diseases].
AB  - The pattern of concomitant diseases has been studied in 708 patients operated on
      for progressive pulmonary tuberculosis. The incidence of concomitant diseases has
      been found to considerably increase in recent years and it was as high as 77%.
      Peptic ulcer and chronic viral hepatitis were responsible for 1.5- and 6-fold
      increases, respectively, in the incidence of concomitant diseases. Virtually all
      diseases accompanying pulmonary tuberculosis were ascertained to cause an
      increase in the frequency of postoperative complications. Diabetes mellitus and
      chronic viral hepatitis concurrent with tuberculosis had the greatest negative
      impact on the course of a postoperative period. These diseases and peptic ulcer
      substantially worsened the long-term results of surgical treatment, by increasing
      the frequency of postoperative recurrences of tuberculosis.

PMID- 16405089
TI  - [The diagnosis and treatment of acute pulmonary circulatory disorders after
      resection for tuberculosis].
AB  - The authors analyzed postoperative complications after 4174 pulmonectomies for
      tuberculosis in the period of 1982-2004. The verified cases of acute venous
      circulatory disorders in the remnants of the lung after partial resections were
      observed in 12 (0.3%) patients. The main causes of hemorrhagic infarct of the
      part of the lung were erroneous ligation of the vein or its rupture; thrombosis
      of the venous trunk; partial removal of a pulmonary portion with devascularized
      tissue left; extensive intrapulmonary hematomas. In case of acute circulatory
      disorder developed in the resected lung, mortality may amount to as high as 58%
      due to secondary complications (sepsis in the presence of generalized gangrene
      and lung tissue decay, purulent pleurisy with bronchopleurothoracic fistulas,
      arrosion profuse hemorrhage). The above complication is a rare, but extremely
      severe iatrogenic abnormality largely associated with shortcomings of surgical
      techniques.

PMID- 16405091
TI  - [Treatment of multiple osseous lesions in a child with generalized BCG
      infection].

PMID- 16405090
TI  - [Role of a comprehensive genetic prognosis in the treatment and prevention of
      respiratory tuberculosis in adolescents].
AB  - The paper presents the results of a follow-up and treatment of 75 adolescents
      with pulmonary tuberculosis. It assesses the predictive value of different
      alleles of the gene HLA-DRB1 and the genotype of Mycobacterium tuberculosis for
      the clinical course of pulmonary tuberculosis in the adolescents. An algorithm of
      examination of an adolescent with tuberculosis has been developed, by using a
      complex of genetic parameters. A differential approach to tuberculosis prevention
      and treatment regimens is presented by taking into account of genetic
      characteristics of gross and microorganisms.

PMID- 16405092
TI  - [Tuberculosis-controlling measures among the populations of increased study
      complexity and epidemic significance].
AB  - The obtained data confirm the epidemic significance and study complexity of
      populations with the limited fluorographic capacities, homeless persons and
      residents of inaccessible settlements of the Far North, as well as the necessity
      of applying special approaches to delivering antituberculous aid in these groups.
      A system has been developed for the epidemiological surveillance and detection of
      tuberculosis in the populations of increased study complexity and epidemic
      significance.

PMID- 16405093
TI  - [More rapid detection of multidrug resistance of Mycobacterium tuberculosis in
      the use of a semiliquid culture medium].
AB  - The paper the results of assays of 649 Mycobacterium tuberculosis strains for
      their drug resistance, by applying the Soton semiliquid medium, which were
      conducted in 1999 to 2004. The sensitivity and specificity of the assay of the
      strains for their resistance to streptomycin, isoniazid, rifampicin, and
      ethambutol have been estimated. These are 89.9 and 97.1%, 96.3 and 87.4%, 95.8
      and 93.1%, and 65.8 and 89.2%, respectively. On day 7, resistance to
      streptomycin, isoniazid, and rifampicin was found by the semiliquid medium in
      90.2% of the cases of 325 multidrug-resistant strains. Multidrug resistance could
      be determined in 80.2% of the strains by the first signs of their growth, i.e. on
      days 3-5. The proposed method is cost-effective and accessible to any practical
      laboratory.

PMID- 16405094
TI  - [Role of islacet (an extract from Island cethraria thalluses) in the complex
      therapy of experimental tuberculosis].
AB  - In vitro experiments showed that islacet produced an inhibitory effect on the
      growth of laboratory drug-sensitive Mycobacterium strains when used at a
      concentration of 25 microg/ml. A considerable reduction in death rates and a
      significant decrease in the mass index and in the indices of pulmonary lesion and
      bacterial isolation from splenic homogenates were observed on the model of
      generalized tuberculosis in mice and rabbits given islacet. In parallel with the
      higher efficiency of therapy using islacet, there was ConA- and PPD- stimulated
      proliferation of splenocytes and their production of interleukin-2 drastically
      inhibited in mice that had long received multidrug therapy (HRZ and HRE). Islacet
      was found to enhance the functional activity of phagocytes and that inhibited
      during the development of infection and under the influence of long-term (more
      than 1 month) etiotropic therapy: the generation of superoxide by murine
      peritoneal macrophages and rabbit neutrophils, as well as by the absorptive and
      digestive function of peritoneal macrophages.

PMID- 16405096
TI  - [A case of complete diaphragmatic relaxation in a patient after left-sided
      pneumonectomy for pulmonary tuberculosis].

PMID- 16405095
TI  - [Anterior mediastinal teratoma with completely formed maxillary portion].

PMID- 16405097
TI  - [Skin tuberculosis: pathogenesis and differential diagnosis. Part 1].

PMID- 16405098
TI  - [Historical reference: giant multinuclear cells in tubercular granuloma].
AB  - By studying the background materials, the authors have analyzed N. I. Pirogov's
      works on the pathological anatomy of tuberculosis. They show the fallacy of the
      widespread statement on N. I. Pirogov's priority in describing one of the
      characteristic cell elements of tuberculous granulation tissue, namely
      multinuclear giant cells referred in the Russian literature to as Pirogov
      Langhans cells.

PMID- 16405099
TI  - [Value of Academician P. G. Kornev's scientific works in solving the present-day
      problems of phthisiology and surgery].

PMID- 16405100
TI  - Technical description of the B-Lynch brace suture for treatment of massive
      postpartum hemorrhage and review of published cases.
AB  - Massive uncontrolled hemorrhage after childbirth is a leading cause of the
      pregnancy-related death and resulting morbidity. Uterine atony is the most common
      cause (75-90%) of primary postpartum hemorrhage. When simple massage of the
      uterus and uterotonics such as oxytocins, syntometrine and prostaglandins failed
      to manage this condition, various surgical solutions have been sought, including
      uterine artery ligation, more complicated stepwise devascularization of the
      uterus, internal iliac artery ligation and, ultimately, hysterectomy. All these
      procedures require above average surgical skill. In contrast, the B-Lynch
      suturing technique (brace suture) is particularly useful because of its
      simplicity of application, life saving potential, relative safety and capacity
      for preserving the uterus and subsequent fertility. The adequacy of haemostasis
      can be assessed both before and immediately after application of the suture. Only
      if it fails need other more radical surgical methods be considered. The special
      advantage of this innovative technique is that it presents an alternative to
      major surgical procedures for controlling pelvic arterial pulse pressure or
      hysterectomy. To date, this suturing technique, when applied correctly, has been
      successful with no problems and no apparent complications. This review provides
      an update on the B-Lynch brace suturing technique, including choice of suture
      material, use of the technique in early and late gestation, and comparison with
      other uterine compression surgical techniques. It also includes a comprehensive
      review and analysis of all published cases and their postoperative follow-up.

PMID- 16405101
TI  - B-Lynch suture: a case series.
AB  - OBJECTIVE: To report an 8-year institutional experience in the use of the B-Lynch
      Suture for the management of postpartum hemorrhage (PPH). STUDY DESIGN: Cases
      with B-Lynch suture utilization for severe postpartum hemorrhage were identified,
      from March 1997 to March 2005, at White Memorial Medical Center. Case charts were
      reviewed, and postoperative follow-up after hospital discharge was conducted by
      telephone interview and outpatient clinic chart review. Historical
      characteristics and outcome of these patients are described. RESULTS: B-Lynch
      suture was performed on 22 patients, between March 1997 and March 2005, to
      control intractable PPH at cesarean section that did not respond to uterotonic
      agents. In 12 instances, the B-Lynch suture was the only intervention, whereas in
      10 it was combined with vessel ligation. The procedure resulted in control of
      bleeding with uterine preservation in 77% of the cases. In those cases where the
      etiology of PPH was uterine atony, the B-Lynch suture was successful in 85% of
      the cases. Hysterectomy was avoided in 17/22 cases. CONCLUSION: The B-Lynch
      suture is an alternative surgical procedure for uterine preservation that may be
      used to control postpartum hemorrhage from uterine atony.

PMID- 16405102
TI  - The obstetric performance of United Kingdom asylum seekers from Somalia: a case
      control study and literature review.
AB  - BACKGROUND: Little published research exists regarding obstetric performance of
      immigrant women in the United Kingdom. The aim of this study was to evaluate the
      obstetric performance and fetal outcomes of Somalian women who received prenatal
      care and requested to deliver at a teaching hospital in North London. METHOD:
      This is a case-control study in which consecutive Somalian women were identified
      as index cases and the subsequent British-born Caucasian women listed in the
      delivery book served as controls. RESULTS: 69 index and 69 control cases were
      analyzed. Fifty-five percent of the Somalian women spoke little or no English.
      Half (50%) had undergone circumcision, the majority being type I WHO
      classification of female genital circumcision, which did not require significant
      surgical intervention prior to labor; 13% had cesarean sections, 13% instrumental
      vaginal deliveries, and 74% had vaginal deliveries. The Somalian women had higher
      parity (2.35 vs. 1.18) and were more likely to be grand multiparous (9/69 vs.
      1/69) compared to controls. Epidural use was less frequent in Somalian women, but
      otherwise there were no significant differences between the two groups with
      regard to maternal age, rates of induction of labor, cesarean sections, duration
      of labor, premature deliveries, instrumental deliveries, and birth weights.
      CONCLUSIONS: The demographic characteristics of the Somalian female population
      appear to exert minimal effect on obstetric and fetal outcomes. This may be due
      to the increased vigilance exercised by health professionals as well as to the
      fact that recent arrivals are from more urban and westernized areas in Somalia.

PMID- 16405103
TI  - Psychological implications of high-risk pregnancy.
AB  - The psychological adjustments of "normal" pregnancy are complex, and those of
      high-risk pregnancy are even more pronounced and severe. A pregnancy may be
      determined to be at high risk because of obstetric factors in previous
      pregnancies or the present one; more general medical factors, such as preexisting
      or emergent disease (often, diabetes); and conditions that are, themselves,
      psychosocial: anxiety disorders (GAD, OCD, panic disorder, PTSD), mood disorders,
      and schizophrenia, all of which are a background for a disturbed pregnancy and
      might complicate a pregnancy denominated high risk for some other reason. This
      paper discusses these concepts and, in addition, includes sections on pregnancy
      in adolescence, in the developmentally disabled, and in the situation of chemical
      dependence (substance abuse).

PMID- 16405104
TI  - Complete failed fertilization after intracytoplasmic sperm injection--analysis of
      10 years' data.
AB  - OBJECTIVE: To investigate incidence and causes of complete failed fertilization
      after intracytoplasmic sperm injection (ICSI) in a tertiary care facility.
      METHODS: A total of 1,779 cycles between February 1994 and December 2003 were
      analyzed. Study parameters were female age, infertility diagnosis, ovarian
      stimulation protocol, estradiol level on day of hCG administration, number of
      follicles, number of oocytes retrieved, number of oocytes injected, and semen
      parameters. RESULTS: Complete failed fertilization occurred in 23 cycles (1.29%)
      involving a total of 85 oocytes injected. Infertility causes among patients with
      failed fertilization included unexplained (43.6%), male factor (26%), presence of
      more than one factor (17.4%), hysterectomy (4.4%), premature ovarian failure
      (4.3%), and advanced age (4.3%). In 12 cycles (52%), fewer than 5 follicles were
      present. In three (13%) cycles, no mature (MII) oocyte was available and in 61%
      (14/23) fewer than 3 MII oocytes were available for ICSI. Immotile sperm was used
      for ICSI in 5 cycles (21.7%). The source of sperm in 17 (74%) cycles was from
      ejaculate, in 4 cycles from testicular aspiration (TESA), one from percutaneous
      epididymal sperm aspiration (PESA) and one from retrograde ejaculation.
      CONCLUSIONS: Our data indicate that major contributing factors to failed
      fertilization after intracytoplasmic sperm injection are number of MII oocytes
      retrieved and availability of viable sperm for injection. Although the incidence
      of complete failed fertilization is not remarkable, it may increase with
      increasing patient age and a lower number of follicles.

PMID- 16405105
TI  - A model of the reflection of activation wavefronts in the heart ventricles of the
      sheep onto the epicardium and body surface.

PMID- 16405106
TI  - Quantitative characteristics of negative inotropic effect of acetylcholine on the
      heart of the snail Helix pomatia.

PMID- 16405107
TI  - Hormones of the pituitary-adrenal system in the mechanisms of unconditioned and
      conditioned reflex reinforcement.

PMID- 16405108
TI  - Marinobufagenin, an endogenous inhibitor of alpha-1 Na/K-ATPase, is a novel
      factor in pathogenesis of diabetes mellitus.

PMID- 16405109
TI  - Influence of geomagnetic activity on mustophoran hematotoxicity.

PMID- 16405110
TI  - Physiological metrology.

PMID- 16405111
TI  - Study of the spatiotemporal kinetics of the contractile activity of the frog back
      lymphatic hearts.

PMID- 16405112
TI  - Characteristics of the structure of minor variants of external transcribed
      spacers of ribosomal DNA of the cockroach Blattella germanica.

PMID- 16405113
TI  - The role of the macrosymbiont genotype in the optimization of nitrogen regimen of
      soils.

PMID- 16405114
TI  - The mechanism of defensive morph formation in Daphnia pulex (Cladocera,
      Daphniidae).

PMID- 16405115
TI  - Changes in the genetic diversity of European Saiga tatarica during a drastic
      population depression.

PMID- 16405116
TI  - Ural chromosomal Serov race of common shrew Sorex araneus L. (Insectivora,
      Mammalia) that inhabits polydominant deep coniferous taiga in the north of
      European Russia.

PMID- 16405117
TI  - A unique diploid-tetraploid unisexual-bisexual fish complex (Pisces, Cobitidae).

PMID- 16405118
TI  - Stimulation of barley seed germination by micromolar aqueous solutions of
      silatrane and cresacin.

PMID- 16405119
TI  - The genetics of shell pigmentation of the Mediterranean mussel Mytilus
      galloprovincialis Lamarck, 1819 (Bivalvia, Mytilida).

PMID- 16405120
TI  - Self-purification of water current and the role of microbiological transformation
      of organic matter in the system of the Selenga River and its delta.

PMID- 16405121
TI  - Analysis of distribution of artificial radionuclides in the ecological system of
      Barents Sea.

PMID- 16405122
TI  - Functioning of the pelagic ecosystems of aquatic areas covered with ice in the
      Barents and Kara Seas in winter and spring.

PMID- 16405123
TI  - Reproductive potential and gene variation in mound-building (Mus spicilegus) and
      house (Mus musculus s. str.) mouse populations as a result of their evolution.

PMID- 16405124
TI  - The fate of backcross offspring of apomeiotic maize x gamagrass hybrids.

PMID- 16405125
TI  - The choice of parental strategy in larids depends on the success in territorial
      competition.

PMID- 16405126
TI  - Transactivation of the epidermal growth factor receptor by oxidized glutathione
      and its pharmacological analogue Glutoxim in A431 cells.

PMID- 16405127
TI  - Characteristic features of function of morphofunctional zones in normal
      epithelium, breast fibroadenoma, and breast cancer.

PMID- 16405128
TI  - Mouse embryo reconstruction as an adequate model for developing the principles of
      therapeutic cloning.

PMID- 16405129
TI  - The peptide of sequence 66-77 of monocytic chemotactic protein (MCP-1) inhibits
      inflammation in experimental animals.

PMID- 16405130
TI  - Mechanisms of intracellular osmolarity changes during the cycles of cleavage
      division in early embryogenesis of mice.

PMID- 16405131
TI  - Prooxidant and cytotoxic effects of thiols combined with vitamin B12b.

PMID- 16405133
TI  - Recommended effect size statistics for repeated measures designs.
AB  - Investigators, who are increasingly implored to present and discuss effect size
      statistics, might comply more often if they understood more clearly what is
      required. When investigators wish to report effect sizes derived from analyses of
      variance that include repeated measures, past advice has been problematic. Only
      recently has a generally useful effect size statistic been proposed for such
      designs: generalized eta squared (eta2G; Olejnik & Algina, 2003). Here, we
      present this method, explain that eta2G preferred to eta squared and partial eta
      squared because it provides comparability across between-subjects and within
      subjects designs, show that it can easily be computed from information provided
      by standard statistical packages, and recommend that investigators provide it
      routinely in their research reports when appropriate.

PMID- 16405134
TI  - Category norms for 500 Spanish words in five semantic categories.
AB  - This study presents a database of 500 words from five semantic categories:
      animals, body parts, furniture, clothing, and intelligence. Each category
      contains 100 words, and data on lexical availability, age of acquisition,
      imageability, typicality, concept familiarity, written word frequency, and word
      length in number of syllables are provided with each word. The full set of norms
      may be downloaded from www.psychonomic.org/archive.

PMID- 16405132
TI  - Spermatogenic structure in the long-lived SAMP1 mice prone to accelerated aging.

PMID- 16405135
TI  - Japanese normative set of 359 pictures.
AB  - This study provides Japanese normative measures for 359 line drawings, including
      260 pictures (44 redrawn) taken from Snodgrass and Vanderwart (1980). The
      pictures have been standardized on voice key naming times, name agreement, age of
      acquisition, and familiarity. The data were compared with American, Spanish,
      French, and Icelandic samples reported in previous studies. In general, the
      correlations between variables in the present study and those in the other
      studies were relatively high, except for name agreement. Naming times were
      predicted in multiple regression analyses by name agreement. The full set of the
      norms and the new pictures may be downloaded from www.psychonomic.org/archive/.

PMID- 16405136
TI  - Picture naming in 3- to 8-year-old French children: methodological considerations
      for name agreement.
AB  - Picture naming has become an important experimental paradigm in cognitive
      psychology. Young children are more variable than adults in their naming
      responses and less likely to know the object or its name. A consequence is that
      the interpretation of the two classical measures used by Snodgrass and Vanderwart
      (1980) for scoring name agreement in adults (the percentage of agreement, based
      on modal name, and the H statistic, based on alternative names) will differ
      because of the high rate of "don't know object" responses, common in young
      children, relative to the low rate of "don't know object" responses more
      characteristic of adults. The present study focused on this methodological issue
      in young French children (3-8 years old), using a set of 145 Snodgrass-Vanderwart
      pictures. Our results indicate that the percentage of agreement based on the
      expected name is a better measure of picture-naming performance than are the
      commonly used measures. The norms may be downloaded from
      www.psychonomic.org/archive.

PMID- 16405138
TI  - The optimal correction for estimating extreme discriminability.
AB  - Discriminability measures such as d' and log d become infinite when performance
      is extremely accurate and no errors are recorded. Different arbitrary corrections
      can be applied to produce finite values, but how well do these values estimate
      true performance? To answer this question, we directly calculated the effects of
      a range of different corrections on the sampling distributions of d' and log d.
      Many arbitrary corrections produced better estimates of discriminability than did
      the intuitively plausible technique of rerunning problem conditions. We concluded
      that when it is not possible to run more trials and when other techniques are not
      appropriate, the best correction overall is to add a correction constant between
      0.25 and 0.5 to all response counts, regardless of their value.

PMID- 16405137
TI  - A comparison of the randomization test with the F test when error is skewed.
AB  - I compared the randomization/permutation test and the F test for a two-cell
      comparative experiment. I varied (1) the number of observations per cell, (2) the
      size of the treatment effect, (3) the shape of the underlying distribution of
      error and, (4) for cases with skewed error, whether or not the skew was
      correlated with the treatment. With normal error, there was little difference
      between the tests. When error was skewed, by contrast, the randomization test was
      more sensitive than the F test, and if the amount of skew was correlated with the
      treatment, the advantage for the randomization test was both large and positively
      correlated with the treatment. I conclude that, because the randomization test
      was never less powerful than the F test, it should replace the F test in routine
      work.

PMID- 16405139
TI  - Using the score method to construct asymmetric confidence intervals: an SAS
      program for content validation in scale development.
AB  - Expert review sessions are often conducted to determine the content validity of
      scale items. The accurate quantification of content validity is usually limited
      by a relatively small number of experts as well as by a small number of rating
      categories. These factors, combined with the bounded and discrete nature of
      rating scale categories, hinder use of traditional methods for computing standard
      errors and confidence intervals. Using an application of the score method,
      researchers can construct an asymmetric interval that is better suited for these
      situations. SAS code is provided to automate the computations, and a discussion
      of two methods for using the obtained results for content validation decision
      making follows.

PMID- 16405140
TI  - An outdoor 3-D visual tracking system for the study of spatial navigation and
      memory in rhesus monkeys.
AB  - Previous studies of the navigational abilities of nonhuman primates have largely
      been limited to what could be described by a human observer with a pen and paper.
      Consequently, we have developed a system that uses a pair of cameras to
      automatically obtain the three-dimensional trajectory of rhesus monkeys
      performing an outdoor spatial navigation and memory task. The system provides
      trajectories, path length, speed, and other variables that would be impossible
      for an unaided observer to note. From trajectory data, we computed and validated
      a path-length measurement. We use this measurement to compare the navigation
      abilities of several animals. In addition, we provide quantitative data on the
      accuracy of a method for automatic behavior detection. Currently, the system is
      being used to examine the sex differences in spatial navigation of rhesus
      monkeys. We expect that measures derived from the trajectory data will reveal
      strategies used by animals to solve spatial problems.

PMID- 16405141
TI  - VRVision: a new tool for the display of 3-D images in behavioral research.
AB  - Researchers using three-dimensional (3-D) scenes in their studies often spend a
      lot of time prerendering the scenes into a set of images for later presentations.
      To improve efficiency, we have developed a new plug-in program for MATLAB that
      eliminates this step. The program is able to manipulate and present 3-D scenes in
      real time. It allows fine control over numerous parameters, including the mode of
      projection, angular rotation, lighting, surface photo textures, and animation.
      Images can be presented with monoscopic or stereoscopic display. It can also
      dynamically track viewer position and update and display an appropriate 3-D
      projection. The program is fully compatible with existing MATLAB utilities such
      as the Psychophysics Toolbox (psychtoolbox.org). It is made freely available to
      the research community (www.hive.hull .ac.uk/software/vrvision).

PMID- 16405142
TI  - A web-based program for coding open-ended response protocols.
AB  - A Web-based coding application was designed to improve coding efficiency and to
      provide a systematic means of evaluating responses to open-ended assessments. The
      system was developed for use by multiple raters to assign open-ended responses to
      predetermined categories. The application provides a software environment for
      efficiently supervising the work of coders and evaluating the quality of the
      coding by (1) systematically presenting open-ended responses to coders, (2)
      tracking each coder's categorized responses, and (3) assessing interrater
      consistency at any time in order to identify coders in need of further training.
      In addition, the application can be set to automatically assign repeated
      responses to categories previously identified as appropriate for those responses.
      To evaluate the efficacy of the coding application and to determine the
      statistical reliability of coding open-ended data within this application, we
      examined data from two empirical studies. The results demonstrated substantial
      interrater agreement on items assigned to various categories across free and
      controlled association tasks. Overall, this new coding application provides a
      feasible method of reliably coding open-ended data and makes the task of coding
      these data more manageable.

PMID- 16405143
TI  - Synchronizing programs using macromedia director plug-ins: an example from the
      field of developmental psychopathology.
AB  - Synchronizing the display of a stimulus with physiological recording or subjects'
      behavioral responses is crucial for acquiring valid measures of performance. This
      article describes a technique for integrating the presentation of stimuli,
      behavior reports, and physiological data employing Macromedia Director and a
      standard biometric program using an example from the field of developmental
      psychopathology. Our experience has been that the use of this technique is
      effective in creating complex protocols for research. Although the temporal
      accuracy available from this particular method is adequate for some experiments,
      it is not suited for investigations requiring single millisecond accuracy.
      Considerations and suggestions for utilizing this and similar techniques for
      integrating data collection and stimuli presentation are discussed.

PMID- 16405144
TI  - Magnifying effects on visual word recognition: a dynamic display for internet
      based experiments.
AB  - A visual presentation procedure is introduced that presents target words followed
      by a dynamic mask until recognition. This form of stimulus degradation prolongs
      the word recognition process. Differences in word recognition latencies-which are
      usually quite small--are magnified, and thus can be more easily observed. The
      results of two experiments on the Internet with a total of 141 participants
      establish the task's ability to magnify differences in word recognition latencies
      stemming from word familiarity (Experiment 1) and word prototypicality
      (Experiment 2). Both factors interact with stimulus degradation, but at different
      presentation intervals; these results are discussed as evidence for comparing
      models of word recognition. The new procedure can be used for assessing
      individual differences, such as implicit motives and self-focused attention.
      Further applications are discussed.

PMID- 16405145
TI  - The reliability and validity of two ambulatory monitoring actigraphs.
AB  - Evidence for the reliability and validity of two models of Ambulatory Monitoring,
      Inc. actigraphs was obtained by testing four instruments of each kind 10 times
      each on a precision pendulum. Correlation and coefficient of variation methods
      were used to analyze the data. Reliability coefficients of .98 were obtained for
      both models. Coefficient of variation methods yielded reliability coefficients of
      92% for the MotionLogger model and 97% for the BuzzBee model. Validity
      coefficients of.99 were obtained for both models. However, MotionLogger means
      were found to differ by up to 36% from one instrument to another, whereas BuzzBee
      means differed by 10% at most. Issues of standardization and measurement units
      were discussed.

PMID- 16405146
TI  - An automated version of the operation span task.
AB  - We present an easy-to-administer and automated version of a popular working
      memory (WM) capacity task (operation span; Ospan) that is mouse driven, scores
      itself, and requires little intervention on the part of the experimenter. It is
      shown that this version of Ospan correlates well with other measures of WM
      capacity and has both good internal consistency (alpha = .78) and test-retest
      reliability (.83). In addition, the automated version of Ospan (Aospan) was shown
      to load on the same factor as two other WM measures. This WM capacity factor
      correlated with a factor composed of fluid abilities measures. The utility of the
      Aospan was further demonstrated by analyzing response times (RTs) that indicated
      that RT measures obtained in the task accounted for additional variance in
      predicting fluid abilities. Our results suggest that Aospan is a reliable and
      valid indicator of WM capacity that can be applied to a wide array of research
      domains.

PMID- 16405147
TI  - A portable version of the go/no-go association task (GNAT).
AB  - The present article describes a portable version of the go/no-go association task
      (GNAT) that runs on Palm Pilot and Handspring personal digital assistant (PDA)
      devices. The PDA version of the GNAT was modeled after a portable version of the
      Implicit Association Test (Dabbs, Bassett, & Dyomina, 2003) and was designed to
      facilitate measurement of implicit social cognition in field settings and among
      difficult-to-reach populations. The PDA version of the GNAT was used to assess
      implicit attitudes about smoking among 11 smokers and 28 nonsmokers. Support for
      the validity of the PDA version of the GNAT was provided by findings that smokers
      showed less negative implicit attitudes toward smoking, as measured by the GNAT,
      than did nonsmokers and that these implicit attitudes were positively correlated
      with self-reported smoking attitudes among both groups.

PMID- 16405148
TI  - The extended Maxwellian view (BIGMAX): a high-intensity, high-saturation color
      display for clinical diagnosis and vision research.
AB  - We describe a device that can display very high intensity (up to 400,000 cd/m2),
      high-resolution visual stimuli. The device is inexpensive, is easily controlled
      by a conventional computer and video card, and can be calibrated for use in
      vision research or clinical applications. The display is capable of presenting
      highly saturated, near spectral colors. Unlike Maxwellian view optical systems,
      our display can be viewed binocularly and does not require exacting head
      restraint. We describe the construction, give a design example, and describe our
      calibration procedure. Furthermore, we report measurements of the color gamut,
      spatial resolution, temporal characteristics, and the dynamic range of light
      intensity.

PMID- 16405150
TI  - Evidence for several components of word familiarity.
AB  - Familiarity with a word can be divided into two main components: familiarity with
      the form of the word (due to both its lexicality and its specific form) and
      familiarity with its meaning. In this study, ratings of familiarity were compared
      for words whose meaning was unknown to participants (UM words), for words of
      known meaning (KM words), and for unknown words (U words). Linguistic and
      experiential frequencies were equivalent. Rated familiarity was lower for UM than
      KM words and even lower for U words. Next, we built pseudowords from these
      stimuli by changing one letter and submitted them to two familiarity rating tasks
      that differed in the nature of the additional stimuli: either only nonwords or
      nonwords plus words. It was assumed that familiarity ratings would be lower for
      pseudowords built from UM words than for pseudowords built from KM words. The
      data were consistent with this assumption, and ratings depended on the initial
      categories of stimuli. These results support the view that usual word familiarity
      has two components, familiarity with form and familiarity with meaning, and a
      double source, processing of word form and processing of word meaning. The full
      set of these materials and norms may be downloaded from
      www.psychonomic.org/archive.

PMID- 16405149
TI  - On the use of microwave radar devices in chronobiology studies: an application
      with Periplaneta americana.
AB  - Modified motion detectors can be used to monitor locomotor activity and measure
      endogenous rhythms. Although these devices can help monitor insects in their home
      cages, the small size of the animals requires a very short wavelength detector.
      We modified a commercial microwave-based detection device, connected the
      detector's output to the digital input of a computer, and validated the device by
      recording circadian and ultradian rhythms. Periplaneta americana were housed in
      individual cages, and their activity was monitored at 18 degrees C and
      subsequently at 28 degrees C in constant darkness. Time series were analyzed by a
      discrete Fourier transform and a chi-square periodogram. Q10 values and the
      circadian free-running period confirmed the data reported in the literature,
      validating the apparatus. Moreover, the spectral analysis and periodogram
      revealed the presence of ultradian rhythmicity in the range of 1-8 h.

PMID- 16405151
TI  - A speeded coding task using a computer-based mouse response.
AB  - This study assessed whether a speeded coding task that used a computer-based
      mouse response (CBMR) format was a measure of general processing speed (Gs). By
      analyzing the task within a network of tasks representing both traditional Gs
      tests and reaction time tasks, it was shown that a CBMR test can be used to
      measure the same construct as traditional paper-and-pencil (PP) tests and that
      this response format does not introduce variance associated with psychomotor
      performance. Differences between PP and CBMR formats were observed, and it is
      argued that these may provide information on individual differences in
      performance not available from traditional coding tests.

PMID- 16405152
TI  - Assessing current adaptation and phylogenetic inertia as explanations of trait
      evolution: the need for controlled comparisons.
AB  - The determination of whether the pattern of trait evolution observed in a
      comparative analysis of species data is due to adaptation to current
      environments, to phylogenetic inertia, or to both of these forces requires that
      one control for the effects of either force when making an assessment of the
      evolutionary role of the other. Orzack and Sober (2001) developed the method of
      controlled comparisons to make such assessments; their implementation of the
      method focussed on a discretely varying trait. Here, we show that the method of
      controlled comparisons can be viewed as a meta-method, which can be implemented
      in many ways. We discuss which recent methods for the comparative analysis of
      continuously distributed traits can generate controlled comparisons and can
      thereby be used to properly assess whether current adaptation and/or phylogenetic
      inertia have influenced a trait's evolution. The implementation of controlled
      comparisons is illustrated by an analysis of sex-ratio data for fig wasps. This
      analysis suggests that current adaptation and phylogenetic inertia influence this
      trait.

PMID- 16405153
TI  - The coevolutionary dynamics of antagonistic interactions mediated by quantitative
      traits with evolving variances.
AB  - Quantitative traits frequently mediate coevolutionary interactions between
      predator and prey or parasite and host. Previous efforts to understand and
      predict the coevolutionary dynamics of these interactions have generally assumed
      that standing genetic variation is fixed or absent altogether. We develop a
      genetically explicit model of coevolution that bridges the gap between these
      approaches by allowing genetic variation itself to evolve. Analysis of this model
      shows that the evolution of genetic variance has important consequences for the
      dynamics and outcome of coevolution. Of particular importance is our
      demonstration that coevolutionary cycles can emerge in the absence of stabilizing
      selection, an outcome not possible in previous models of coevolution mediated by
      quantitative traits. Whether coevolutionary cycles evolve depends upon the
      strength of selection, the number of loci, and the rate of mutation in each of
      the interacting species. Our results also generate novel predictions for the
      expected sign and magnitude of linkage disequilibria in each species.

PMID- 16405154
TI  - Disturbance induces the contrasting evolution of reinforcement and dispersiveness
      in directed and random movers.
AB  - Spatial models commonly assume that dispersal rates are constant across
      individuals and environments and that movement directions are unbiased. These
      random-movement assumptions are inadequate to capture the range of dispersal
      behaviors revealed in diverse case studies. We examine an alternative assumption
      of directed movement, in which dispersal is a conditional and directional
      response by individuals to varying environmental conditions. Specifically, we
      assume individuals bias their movements to climb spatial fitness gradients. We
      compare the consequences of random and directed movement for local adaptation,
      the evolution of dispersal, and the reinforcement process. The implications of
      each movement strategy depend on the nature of environmental disturbance, and we
      examine the outcomes for undisturbed environments and with uncorrelated and
      autocorrelated disturbances. Both movement strategies offer advantages over
      sedentary life histories by allowing colonization of suitable habitats. However,
      random movement eventually becomes costly in stable environments because it
      inhibits local adaptation. In contrast, directed movement accelerates local
      adaptation. In disturbed environments, random movement offers bet-spreading
      advantages by distributing offspring across habitats. Despite being a more
      targeted strategy, an intermediate amount of directed movement provides similar
      bet-spreading benefits. These fitness consequences have implications for the
      evolution of dispersal. Dispersiveness is lost by random movers in undisturbed
      environments, is maintained in polymorphism with infrequent disturbances, and
      evolves when disturbances are uncorrelated. Directed movement becomes selectively
      neutral in the absence of disturbance, evolves when disturbances are
      autocorrelated, and is maintained in polymorphism with uncorrelated disturbances.
      Disturbance also determines the outcome of the reinforcement process for each
      strategy. For example, directed movers show no progress toward reinforcement in
      undisturbed environments, evolve random mating with uncorrelated disturbances,
      and can evolve assortative mating in infrequently disturbed environments.

PMID- 16405155
TI  - Female mate-choice behavior and sympatric speciation.
AB  - Many models have investigated how the process of speciation may occur in
      sympatry. In these models, individuals are either asexual or mate choice is
      determined by very simple rules. Females, for example, may be assumed either to
      compare their phenotype to that of a potential mate, preferring to mate with
      similar males (phenotype matching), or to possess preference genes that determine
      which male phenotype they prefer. These rules often do not reflect the mate
      choice rules found in empirical studies. In this paper, we compare these two
      modes of female choice with various types of sexual imprinting. We examine the
      efficacy of different mate-choice behavior in causing divergence in male traits
      under simple deterministic one-locus population genetic models as well as under
      polygenic, individual-based simulations based on the models of Dieckmann and
      Doebeli (1999). We find that the inheritance mechanism of mate choice can have a
      large effect on the ease of sympatric speciation. When females imprint on their
      mothers, the result of the model is similar to phenotype matching, where
      speciation can occur fairly easily. When females imprint on their fathers or
      imprint obliquely, speciation becomes considerably less likely. Finally, when
      females rely on preference genes, male trait evolution occurs easily, but the
      correlation between trait and preference can be weak, and interpreting these
      results as speciation may be suspect.

PMID- 16405157
TI  - Loci affecting long-term hybrid survivorship in Louisiana irises: implications
      for reproductive isolation and introgression.
AB  - Iris fulva and I. brevicaulis are long-lived plant species known to hybridize
      where they coexist in nature. Year-to-year survival contributes significantly to
      overall fitness for both species and their hybrid derivatives, and differences in
      hybrid survivability may have important consequences to interspecific gene flow
      in nature. We examined the genetic architecture of long-term survivorship of
      reciprocal backcross I. fulva x I. brevicaulis hybrids in a common-garden,
      greenhouse environment. Differences in mortality were found between the two
      backcross (BC1) hybrid classes, with hybrids crossed toward I. fulva (BCIF)
      revealing twice the mortality of those hybrids backcrossed toward I. brevicaulis
      (BCIB). Using genomic scans on two separate genetic linkage maps derived from the
      reciprocal hybrid populations, we found that hybrid survivorship is influenced by
      several genetic regions. Multiple interval mapping (MIM) revealed four
      quantitative trait loci (QTLs) in BCIF hybrids that were significantly associated
      with survivorship. Introgressed I. brevicaulis DNA increased survivorship at
      three of the four QTLs. For the fourth QTL, introgressed I. brevicaulis DNA was
      associated with decreased survivorship. No QTLs were detected in BCIB hybrids;
      however, single-marker analysis revealed five unlinked loci that were
      significantly associated with survivorship. At all five markers, survivorship was
      positively associated with introgressed I. fulva DNA. The present findings have
      important implications for the evolutionary dynamics of naturally occurring
      hybrid zones. Regions of the genome that increase survivorship when in a
      heterozygous (i.e., hybrid) state should have an increased likelihood of passing
      across species boundaries, whereas those that decrease survivorship will be less
      likely to introgress.

PMID- 16405156
TI  - Antagonism between sexual and natural selection in experimental populations of
      Saccharomyces cerevisiae.
AB  - Trade-offs between life-history components are a central concept of evolution and
      ecology. Sexual and natural selection seem particularly apt to impose
      antagonistic selective pressures. When sex is not integrated into reproduction,
      as in Saccharomyces cerevisiae, natural selection can impair or even eliminate
      it. In this study, a genetic trade-off between the sexual and asexual phases of
      the yeast life cycle was suggested by sharp declines in the mating and
      sporulation abilities of unrelated genotypes that were propagated asexually in
      minimal growth medium and in mice. When sexual selection was applied to
      populations that had previously evolved asexually, sexual fitness increased but
      asexual fitness declined. No such negative correlation was observed when sexual
      selection was applied to an ancestral strain: sexual and asexual fitness both
      increased. Thus, evolutionary history affected the evolution of genetic
      correlations, as fitness increases in a population already well adapted to the
      environment were more likely to come at the expense of sexual functions.

PMID- 16405158
TI  - Population structure at two geographic scales in the burrowing crustacean
      Callichirus islagrande (Decapoda, Thalassinidea): historical and contemporary
      barriers to planktonic dispersal.
AB  - There has been much recent interest in the extent to which marine planktonic
      larvae connect local populations demographically and genetically. Uncertainties
      about the true extent of larval dispersal have impeded our understanding of the
      ecology and evolution of marine species as well as our attempts to effectively
      manage marine populations. Because direct measurements of larval movements are
      difficult, genetic markers have often been used for indirect measurements of gene
      flow among marine populations. Here we examine data from allozymes, mitochondrial
      DNA sequences, and microsatellite length polymorphisms to assess the extent of
      gene flow among populations of the burrowing crustacean Callichirus islagrande.
      All three types of markers revealed a genetic break between populations separated
      by the Louisiana Chenier Plain. The extent of mitochondrial sequence divergence
      across this break indicates that the nominal species, C. islagrande, consists of
      at least two lineages that have been reproductively isolated for about a million
      years. Within the eastern lineage microsatellite allele frequencies were
      significantly heterogeneous among populations as little as 10 km apart. Maximum
      likelihood estimates of gene flow and effective population size based on a
      coalescent model for the microsatellite data indicated that local populations are
      nearly closed. A model-based clustering method identified four or five groups
      from the microsatellite data, although individuals sampled from each location
      generally consisted of mixtures of these groups. This suggests a mechanism that
      would lead to genetic differentiation of open populations: gene flow from
      different source populations that are themselves genetically distinct.

PMID- 16405159
TI  - Placing the Floridian marine genetic disjunction into a regional evolutionary
      context using the scorched mussel, Brachidontes exustus, species complex.
AB  - The well-documented Floridian Gulf/Atlantic marine genetic disjunction provides
      an influential example of presumed vicariant cladogenesis along a continental
      coastline for major elements of a diverse nearshore fauna. However, it is unclear
      if this disjunction represents a local anomaly for regionally distributed
      morphospecies, or if it is merely one of many such cryptic phylogenetic splits
      that underlay their assumed genetic cohesiveness. We aimed to place the
      previously characterized scorched mussel Gulf/Atlantic genetic disjunction into a
      regional phylogenetic perspective by incorporating genotypes of nominal
      conspecifics sampled throughout the Caribbean Basin as well as those of eastern
      Pacific potential geminate species. Our results show it to be one of multiple
      latent regional genetic disjunctions, involving five cryptic Caribbean species,
      that appear to be the product of a long history of regional cladogenesis.
      Disjunctions involving three stem lineages clearly predate formation of the
      Isthmus of Panama and of the Caribbean Sea, although four of the five cryptic
      species have within-basin sister relationships. Surprisingly, the Atlantic clade
      was also found to be widespread in the southern Caribbean, and ancestral
      demography calculations through time for Atlantic coast-specific genotypes are
      consistent with a northward range extension after the last glacial maximum. Our
      new data seriously undermine the hypothesis of a Floridian vicariant genesis and
      imply that the scorched mussel Gulf/Atlantic disjunction represents a case of
      geographic and temporal pseudocongruence. All five Caribbean Basin cryptic
      species exhibited an intriguing pattern of predominantly allopatric distribution
      characterized by distinct geographic areas of ecological dominance, often
      adjoining those of sister taxa. This pattern of distribution is consistent with
      allopatric speciation origins, coupled with restricted postspeciation range
      extensions. Several lines of indirect evidence favor the hypothesis that the
      predominantly allopatric distributions are maintained over evolutionary time
      scales, primarily by postrecruitment ecological filters rather than by
      oceanographic barriers to larval-mediated gene flow.

PMID- 16405160
TI  - Modeling the adaptive potential of isolated populations: experimental simulations
      using Drosophila.
AB  - The genetic variability underlying many morphological and stress resistance
      traits may largely depend on the effects of genetic drift balanced by polygenic
      mutation. This model of adaptive potential has played a central role in the
      minimum viable population size concept and has been used to predict the effective
      population size necessary to prevent extinction within changing environments.
      However, there have been few long-term experimental studies of adaptive potential
      within isolated populations, and no study has thus far provided an experimental
      test of the drift-mutation model of quantitative genetic variation. Using the
      sternopleural bristle number of Drosophila melanogaster as a model quantitative
      trait, we performed repeated measurements of adaptive potential on 15 replicate
      populations of two and 10 male-female pairs over 30 and 77 generations,
      respectively. Declines in adaptive potential were analyzed by comparing observed
      and expected changes in realized heritability over time. The only significant
      model deviation occurred immediately after bottlenecks of two pairs, in which
      greater than expected declines in realized heritability were observed. This
      result suggests that changes in allelic diversity during bottleneck events may be
      as important as changes in heterozygosity in determining adaptive potential.
      Drift-mutation model expectations were otherwise realized over all generations.
      Our results validate the use of the drift-mutation model as a tool for
      understanding the dynamics of adaptive potential for peripheral fitness
      characters, but suggest caution in applying this model to recently bottlenecked
      populations.

PMID- 16405161
TI  - Genetic drift within a protected polymorphism: enigmatic variation in color-morph
      frequencies in the candy-stripe spider, Enoplognatha ovata.
AB  - The candy-stripe spider, Enoplognatha ovata, exhibits a striking color
      polymorphism comprising three morphs. A number of lines of evidence strongly
      suggest that this polymorphism is maintained by natural selection: its presence
      in a sister species, E. latimana; the physical nature of the variation; the
      virtual lack of monomorphic populations; the highly consistent rank-order of
      morphs within populations; and the presence of large-scale clines associated with
      climatic variables. However, the absence of selection is equally strongly
      suggested by very local surveys of morph frequencies over space and time,
      perturbation experiments, and a variance in morph frequency between populations
      that is virtually independent of spatial scale. In addition, local spatial
      patterns in one study site (Nidderdale, Yorkshire, England) have been explained
      in terms of intermittent drift over half a century ago, a hypothesis supported
      here by the distributions of four other genetic markers (two allozyme and two
      visible polymorphisms). A heuristic model is suggested that reconciles these
      apparently contradictory messages regarding the importance of drift and selection
      in this system. It is proposed that when allele frequencies of the color morph
      redimita lie between approximately 0.05 and 0.3, the deltaq on q plot is very
      shallow, so that within this region, where the majority of populations lie,
      selection is weak and drift is the major force determining local morph
      frequencies. However, outside this range of frequencies, powerful selection acts
      to protect the polymorphism. This model may apply to polymorphisms in other
      species and explain why evidence of selection in natural populations is often
      elusive.

PMID- 16405162
TI  - Breeding system, colony structure, and genetic differentiation in the Camponotus
      festinatus species complex of carpenter ants.
AB  - All social insects live in highly organized societies. However, different social
      insect species display striking variation in social structure. This variation can
      significantly affect the genetic structure within populations and, consequently,
      the divergence between species. The purpose of this study was to determine if
      variation in social structure was associated with species diversification in the
      Camponotus festinatus desert carpenter ant species complex. We used polymorphic
      DNA microsatellite markers to dissect the breeding system of these ants and to
      determine if distinct C. festinatus forms hybridized in their natural range. Our
      analysis of single-queen colonies established in the laboratory revealed that
      queens typically mated with only a single male. The genotypes of workers sampled
      from a field population suggested that multiple, related queens occasionally
      reproduced within colonies and that colonies inhabited multiple nests. Camponotus
      festinatus workers derived from colonies of the same form originating at
      different locales were strongly differentiated, suggesting that gene flow was
      geographically restricted. Overall, our data indicate that C. festinatus
      populations are highly structured. Distinct C. festinatus forms possess similar
      social systems but are genetically isolated. Consequently, our data suggest that
      diversification in the C. festinatus species complex is not necessarily
      associated with a shift in social structure.

PMID- 16405163
TI  - Character displacement as the "best of a bad situation": fitness trade-offs
      resulting from selection to minimize resource and mate competition.
AB  - Character displacement has long been considered a major cause of adaptive
      diversification. When species compete for resources or mates, character
      displacement minimizes competition by promoting divergence in phenotypes
      associated with resource use (ecological character displacement) or mate
      attraction (reproductive character displacement). In this study, we investigated
      whether character displacement can also have pleiotropic effects that lead to
      fitness trade-offs between the benefits of avoiding competition and costs accrued
      in other fitness components. We show that both reproductive and ecological
      character displacement have caused spadefoot toads to evolve smaller body size in
      the presence of a heterospecific competitor. Although this shift in size likely
      arose as a by-product of character displacement acting to promote divergence
      between species in mating behavior and larval development, it concomitantly
      reduces offspring survival, female fecundity, and sexual selection on males.
      Thus, character displacement may represent the "best of a bad situation" in that
      it lessens competition, but at a cost. Individuals in sympatry with the displaced
      phenotype will have higher fitness than those without the displaced trait because
      they experience reduced competition, but they may have reduced fitness relative
      to individuals in allopatry. Such a fitness trade-off can limit the conditions
      under which character displacement evolves and may even increase the risk of
      "Darwinian extinction" in sympatric populations. Consequently, character
      displacement may not always promote diversification in the manner that is often
      expected.

PMID- 16405164
TI  - The adaptive significance of temperature-dependent sex determination:
      experimental tests with a short-lived lizard.
AB  - Why is the sex of many reptiles determined by the temperatures that these animals
      experience during embryogenesis, rather than by their genes? The Charnov-Bull
      model suggests that temperature-dependent sex determination (TSD) can enhance
      maternal fitness relative to genotypic sex determination (GSD) if offspring
      traits affect fitness differently for sons versus daughters and nest temperatures
      either determine or predict those offspring traits. Although potential pathways
      for such effects have attracted much speculation, empirical tests largely have
      been precluded by logistical constraints (i.e., long life spans and late
      maturation of most TSD reptiles). We experimentally tested four differential
      fitness models within the Charnov-Bull framework, using a short-lived, early
      maturing Australian lizard (Amphibolurus muricatus) with TSD. Eggs from wild
      caught females were incubated at a range of thermal regimes, and the resultant
      hatchlings raised in large outdoor enclosures. We applied an aromatase inhibitor
      to half the eggs to override thermal effects on sex determination, thus
      decoupling sex and incubation temperature. Based on relationships between
      incubation temperatures, hatching dates, morphology, growth, and survival of
      hatchlings in their first season, we were able to reject three of the four
      differential fitness models. First, matching offspring sex to egg size was not
      plausible because the relationship between egg (offspring) size and fitness was
      similar in the two sexes. Second, sex differences in optimal incubation
      temperatures were not evident, because (1) although incubation temperature
      influenced offspring phenotypes and growth, it did so in similar ways in sons
      versus daughters, and (2) the relationship between phenotypic traits and fitness
      was similar in the two sexes, at least during preadult life. We were unable to
      reject a fourth model, in which TSD enhances offspring fitness by generating
      seasonal shifts in offspring sex ratio: that is, TSD allows overproduction of
      daughters (the sex likely to benefit most from early hatching) early in the
      nesting season. In keeping with this model, hatching early in the season
      massively enhanced body size at the beginning of the first winter, albeit with a
      significant decline in probability of survival. Thus, the timing of hatching is
      likely to influence reproductive success in this short-lived, early maturing
      species; and this effect may well differ between the sexes.

PMID- 16405165
TI  - Evolutionary pathways in shorebird breeding systems: sexual conflict, parental
      care, and chick development.
AB  - Sexual selection, mating opportunities, and parental behavior are interrelated,
      although the specific nature of these relationships is controversial. Two major
      hypotheses have been suggested. The parental investment hypothesis states that
      the relative parental investment of the sexes drives the operation of sexual
      selection. Thus, the sex that invests less in offspring care competes more
      intensely and monopolizes access to mates. The sexual conflict hypothesis
      proposes that sexual selection (the competition among both males and females for
      mates), mating opportunities, and parental behavior are interrelated and predicts
      a feedback loop between mating systems and parental care. Here we test both
      hypotheses using a comprehensive dataset of shorebirds, a maximum-likelihood
      statistical technique, and a recent supertree of extant shorebirds and allies.
      Shorebirds are an excellent group for these analyses because they display unique
      variation in parental care and social mating system. First, we show that chick
      development constrains the evolution of both parental care and mate competition,
      because transitions toward more precocial offspring preceded transitions toward
      reduced parental care and social polygamy. Second, changes in care and mating
      systems respond to one another, most likely because both influenced and are
      influenced by mating opportunities. Taken together, our results are more
      consistent with the sexual conflict hypothesis than the parental investment
      hypothesis.

PMID- 16405166
TI  - Genetic structure and colonization processes in European populations of the
      common vole, Microtus arvalis.
AB  - The level of genetic differentiation within and between evolutionary lineages of
      the common vole (Microtus arvalis) in Europe was examined by analyzing
      mitochondrial sequences from the control region (mtDNA) and 12 nuclear
      microsatellite loci (nucDNA) for 338 voles from 18 populations. The distribution
      of evolutionary lineages and the affinity of populations to lineages were
      determined with additional sequence data from the mitochondrial cytochrome b
      gene. Our analyses demonstrated very high levels of differentiation between
      populations (overall FST: mtDNA 70%; nucDNA 17%). The affinity of populations to
      evolutionary lineages was strongly reflected in mtDNA but not in nucDNA
      variation. Patterns of genetic structure for both markers visualized in synthetic
      genetic maps suggest a postglacial range expansion of the species into the Alps,
      as well as a potentially more ancient colonization from the northeast to the
      southwest of Europe. This expansion is supported by estimates for the divergence
      times between evolutionary lineages and within the western European lineage,
      which predate the last glacial maximum (LGM). Furthermore, all measures of
      genetic diversity within populations increased significantly with longitude and
      showed a trend toward increase with latitude. We conclude that the detected
      patterns are difficult to explain only by range expansions from separate LGM
      refugia close to the Mediterranean. This suggests that some M. arvalis
      populations persisted during the LGM in suitable habitat further north and that
      the gradients in genetic diversity may represent traces of a more ancient
      colonization of Europe by the species.

PMID- 16405167
TI  - Bats, clocks, and rocks: diversification patterns in Chiroptera.
AB  - Identifying nonrandom clade diversification is a critical first step toward
      understanding the evolutionary processes underlying any radiation and how best to
      preserve future phylogenetic diversity. However, differences in diversification
      rates have not been quantitatively assessed for the majority of groups because of
      the lack of necessary analytical tools (e.g., complete species-level phylogenies,
      estimates of divergence times, and robust statistics which incorporate
      phylogenetic uncertainty and test appropriate null models of clade growth). Here,
      for the first time, we investigate diversification rate heterogeneity in one of
      the largest groups studied thus far, the bats (Mammalia: Chiroptera). We use a
      recent, robust statistical approach (whole-tree likelihood-based relative rate
      tests) on complete dated species-level supertree phylogenies. As has been
      demonstrated previously for most other groups, among-lineage diversification rate
      within bats has not been constant. However, we show that bat diversification is
      more heterogeneous than in other mammalian clades thus far studied. The whole
      tree likelihood-based relative rates tests suggest that clades within the
      families Phyllostomidae and Molossidae underwent a number of significant changes
      in relative diversification rate. There is also some evidence for rate shifts
      within Pteropodidae, Emballonuridae, Rhinolophidae, Hipposideridae, and
      Vespertilionidae, but the significance of these shifts depends on polytomy
      resolution within each family. Diversification rate in bats has also not been
      constant, with the largest diversification rate shifts occurring 30-50 million
      years ago, a time overlapping with the greatest number of shifts in flowering
      plant diversification rates.

PMID- 16405168
TI  - Testing hypotheses about ecological specialization using phylogenetic trees.
AB  - It is often assumed that ecological specialization represents an evolutionary
      "dead-end" that limits further evolution. Maximum-likelihood (ML) analyses on
      phylogenies for 15 groups of phytophagous insects revealed that high transition
      rates both to and from specialization occurred, but that the mean ratio of rates
      was significantly biased toward a higher rate to specialization. Here we explore
      the consequences of the fact that transition rates inferred by ML are affected
      not only by the distribution, but also by the frequency, of character states.
      Higher rates to the more common state were inferred in the analyses of Nosil
      (2002), in similar studies published since 2002, and in a small set of
      simulations. Thus, the ratio of the rate toward versus away from specialization
      was strongly, positively correlated with the proportion of specialist species at
      the tips of the phylogeny and whether transitions away from specialization occur
      remains unclear. Here we reexamine these data using methods that do not rely on
      directly comparing transition rates. Maximum-likelihood analyses show that models
      with no transitions in one direction (e.g., irreversible evolution as predicted
      by the "specialist as dead end" framework) are usually strongly rejected,
      independent of the proportion of specialists at the tips. Ancestral state
      reconstruction revealed two instances where generalists were unambiguously
      derived from specialists. Transition rates would need to biased 100-fold and 5000
      fold toward specialization to reconstruct a history where these shifts from
      specialization toward generalization do not occur. The general conclusions of
      Nosil (2002) appear to hold; transitions in either direction likely occur such
      that specialization does not always limit further evolution. Most generally,
      inferences regarding character evolution can be strengthened by comparing models
      of character change and examining ancestor states, rather than only comparing
      parameter values.

PMID- 16405169
TI  - Multigenerational versus single generation studies to estimate herbicide
      resistance fitness cost in Arabidopsis thaliana.
AB  - The evolution of resistance in response to pesticide selection is expected to be
      delayed if fitness costs are associated with resistance genes. The estimate of
      fitness costs usually involves comparing major growth traits of resistant versus
      susceptible individuals in the absence of pesticide. Ideally, a measure of
      changes in resistance allele frequency over several generations would allow the
      best estimate of the overall fitness cost of a resistance gene. In greenhouse
      conditions, we monitored the dynamics of the evolution of the frequencies of six
      herbicide-resistant mutations (acetolactate synthase, cellulose synthase, and
      auxin-induced target genes) in the model species Arabidopsis thaliana in a
      multigenerational study covering five to seven nonoverlapping generations. The
      microevolutionary dynamics in experimental populations indicated a mean fitness
      cost of 38%, 73%, and 94% for the ixr1-2, axr1-3, and axr2-1 resistances,
      respectively; no fitness cost for the csr1-1, and ixr2-1 resistances; and a
      transient advantage for the aux1-7 resistance. The result for the csr1-1
      resistance contrasts with a cost of 37% based on total seed number in a previous
      study, demonstrating that single generation studies could have limitation for
      detecting cost. A positive frequency dependence for the fitness cost was also
      detected for the ixr1-2 resistance. The results are discussed in relation to the
      maintenance of polymorphism at resistance loci.

PMID- 16405170
TI  - Colony-level impacts of immune responsiveness in honey bees, Apis mellifera.
AB  - Social insects have evolved both communal and individual traits that reduce the
      impacts of their numerous parasites and pathogens. Among the individual traits,
      innate-immune responses have the potential to reduce both individual mortality
      and the spread of pathogens among colony members. An understanding of the costs
      and benefits of such responses can provide a more complete understanding of a
      primary risk of social life, horizontal disease transmission among colony
      members. Here we assess the impacts of individual immunity on colony-level
      disease in honey bee (Apis mellifera) colonies following exposure to an important
      bacterial pathogen (Paenibacillus larvae subsp. larvae, cause of the disease
      American foulbrood). Colony-level disease rates were negatively correlated with
      the immune responsiveness of colony members, as assessed by larval transcript
      levels for the gene encoding the antibacterial peptide abaecin. Concomitantly,
      colonies whose members mounted a stronger abaecin response showed significantly
      lower productivity, indicating a colony-level cost to this immune response. The
      results show considerable variation across colonies in an immune trait important
      for survival, and point toward a significant trade-off between this trait and
      colony productivity.

PMID- 16405171
TI  - Different optimal offspring sizes for sons versus daughters may favor the
      evolution of temperature-dependent sex determination in viviparous lizards.
AB  - Temperature-dependent sex determination (TSD) has evolved independently in at
      least two lineages of viviparous Australian scincid lizards, but its adaptive
      significance remains unclear. We studied a montane lizard species (Eulamprus
      heatwolei) with TSD. Our data suggest that mothers can modify the body sizes of
      their offspring by selecting specific thermal regimes during pregnancy (mothers
      with higher and more stable temperatures produced smaller offspring), but cannot
      influence sons versus daughters differentially in this way. A field mark
      recapture study shows that optimal offspring size differs between the sexes:
      larger body size at birth enhanced the survival of sons but reduced the survival
      of daughters. Thus, a pregnant female can optimize the fitness of either her sons
      or her daughters (via yolk allocation and thermoregulation), but cannot
      simultaneously optimize both. One evolutionary solution to reduce this fitness
      cost is to modify the sex-determining mechanism so that a single litter consists
      entirely of either sons or daughters; TSD provides such a mechanism. Previous
      work has implicated a sex difference in optimal offspring size as a selective
      force for TSD in turtles. Hence, opposing fitness determinants of sons and
      daughters may have favored evolutionary transitions from genetic sex
      determination to TSD in both oviparous turtles and viviparous lizards.

PMID- 16405172
TI  - Synthesis and characterization of chemically bonded stationary phases on hydride
      surfaces by hydrosilation of alkynes and dienes.
AB  - A hydrosilation reaction was used to bind four compounds with one or more alkyne
      groups or two alkene functionalities. The diffuse reflectance infrared Fourier
      transform, the 29Si cross-polarization magic-angle spinning (CP-MAS) NMR, and the
      13C CP-MAS NMR spectra were used to characterize the various bonded materials.
      The bonded phase density was determined from carbon elemental analysis. The two
      ten-carbon hydrophobic stationary phases were characterized chromatographically
      and static stability tests were run in acidic and basic solutions.

PMID- 16405173
TI  - Validation of a novel HPLC sorbent material for the determination of ten
      quinolones in human and veterinary pharmaceutical formulations.
AB  - A novel sorbent material of ultrapure silica gel provided with novel State of the
      Art Bonding- and Endcapping Technology commercially available under the name
      PerfectSil Target (250 x 4 mm, ODS-3, 5 microm, by MZ-Analysentechnik, Germany)
      was used and validated for the sensitive HPLC determination of ten quinolone
      antibiotics: enoxacin, ofloxacin, norfloxacin, ciprofloxacin, danofloxacin (DAN),
      enrofloxacin (ENR), sarafloxacin, oxolinic acid (OXO), nalidixic acid (NAL), and
      flumequine. The analytical column validation was performed in terms of separation
      efficiency, precision, and peak asymmetry. The separation was achieved at ambient
      temperature using a mobile phase of TFA (0.1%)-CH3OH-CH3CN delivered under the
      optimum gradient program, at a flow rate of 1.2 mU/min. Photodiode array
      detection was used and eluant was monitored at 275 nm. For the quantitative
      determination caffeine (7.5 ng/microL) was used as internal standard. The
      achieved LODs were 0.03 ng/microL per 50 microL injected volume for OXO, 0.1
      ng/microL for DAN, ENR, and NAL, and 0.2 ng/microL for the remaining six studied
      quinolones. The method was validated in terms of interday (n = 6) and intraday (n
      = 5) precision and accuracy. The proposed method was successfully applied to the
      analysis of pharmaceutical formulations destined either for human or for
      veterinary use.

PMID- 16405174
TI  - Ketoimine modified silica as an adsorbent for gas chromatographic analysis of
      olefins.
AB  - New adsorbents for capillary complexation GC have been proposed. The adsorbents
      contain free ketoimine groups which enable binding copper(II) and chromium(III)
      chlorides. The adsorbents obtained have been characterised by elemental analysis,
      differential scanning calorimetry and electron spin resonance. The specific
      interactions between the adsorbent and adsorbate molecules have been
      characterised by retention parameters (retention index - I, specific retention
      volume - Vg, molecular retention index - deltaMe). Attempts were also made at
      separating mixtures of olefins.

PMID- 16405175
TI  - Column chromatographic separation of metal ions on 1-(2-pyridylazo)-2-napthol
      modified amberlite IR-120 resin.
AB  - Cation exchange resin, Amberlite IR-120, has been modified by the sorption of 1
      (2-pyridylazo)-2-napthol (PAN) at pH 6.0. The optimum conditions for the sorption
      of PAN on the resin have been established. The maximum sorption of PAN was found
      to be 8.70 micromol/g. In order to explore the separation possibilities of the
      material, distribution coefficients of a number of metal ions were determined in
      various solvent systems. A number of binary separations of metal ions of
      analytical interest have been carried out using columns packed with this
      material. In order to demonstrate the practical utility of this material, Zn2+
      and Hg2+ have been selectively separated from synthetic mixtures of metal ions
      and assay of Zn2+ and Fe2+ in commercially available pharmaceutical tablets;
      namely Fesofor-Z and FE-Z, was carried out.

PMID- 16405176
TI  - Selective extraction of derivates of p-hydroxy-benzoic acid from plant material
      by using a molecularly imprinted polymer.
AB  - Selective SPE of derivates of p-hydroxybenzoic acid (pHBA) from plant extract of
      Melissa officinalis is presented using a molecularly imprinted polymer (MIP) made
      with protocatechuic acid (PA) as template molecule. MIP was prepared with
      acrylamide as functional monomer, ethylene glycol dimethacrylate as crosslinking
      monomer and ACN as porogen. MIP was evaluated towards six phenolic acids: PA,
      gallic acid, pHBA, vanillic acid (VA), gentisic acid (GeA) and syringic acid
      (SyrA), and then steps of molecularly imprinted SPE (MISPE) procedure were
      optimized. The best specific binding capacity of MIP was obtained for PA in ACN
      (34.7 microg/g of MIP). Other tested acids were also bound on MIP if they were
      dissolved in this solvent. ACN was chosen as solvent for sample application. M.
      officinalis was extracted into methanol/water (4:1, v/v), the extract was then
      evaporated to dryness and dissolved in ACN before application on MIP. Water and
      ACN were used as washing solvents and elution of benzoic acids was performed by
      means of a mixture methanol/acetic acid (9:1, v/v). pHBA, GA, PA and VA were
      extracted with recoveries of 56.3-82.1% using this MISPE method. GeA was not
      determined in plant extract.

PMID- 16405178
TI  - Application of silica gel 60 loaded with Aspergillus niger as a solid phase
      extractor for the separation/preconcentration of chromium(III), copper(II),
      zinc(II), and cadmium(II).
AB  - Sorption properties of silica gel 60 loaded with fungi cells characterized as
      Aspergillus niger were evaluated for trace enrichment of Cr(III), Cu(II), Zn(II),
      and Cd(II) from various water samples prior to the description of flame atomic
      absorption spectrometric analysis. The proposed SPE method is cheap, simple,
      highly sensitive, accurate, and selective for enrichment of analytes. The effect
      of experimental parameters, such as pH of sample solution, amount of solid phase,
      eluent type, and volume of sample solution on the recovery of the metal ions has
      been investigated. The effect of diverse ions was also investigated. The
      recoveries of Cr(III), Cu(II), Zn(II), and Cd(II) under the optimum experimental
      conditions were 98 +/- 2, 98 +/- 3, 99 +/- 2, 100 +/- 2%, respectively, at the
      95% confidence level. The analytical detection limits were found to be 3.1, 1.6,
      1.1, and 1.4 microg/L for Cr(III), Cu(II), Zn(II), and Cd(II), respectively. The
      proposed enrichment method was applied to the determination of analytes in
      Ataturk Dam, Egirdir Lake, and tap-water samples. The analytes were determined
      with a relative error lower than 8% in various water samples. The method has been
      validated by analyzing spiked water samples.

PMID- 16405177
TI  - Dynamic ultrasound-assisted extraction of polyphenols in tobacco.
AB  - A novel extraction method, namely dynamic ultrasound-assisted extraction, is
      investigated. This technique is efficient with respect to both time and solvent
      consumption because it utilizes ultrasonic energy in dynamic mode during
      extraction. Polyphenols (chlorogenic acid, esculetin, rutin, scopoletin, and
      quercitrin) are extracted from a tobacco (Nicotina tobaccum L.) sample for 10 min
      with 6 mL of solvent. Fresh solvent is continuously pumped through the sample,
      with which the analytes can be rapidly extracted, and the possibility of
      degradation efficiently avoided. Methanol involving 0.5% w/v ascorbic acid was
      used as extraction solvent; optimal flow rate and extraction time were
      investigated. The extract was cleaned up by C18 disposable cartridge. The spiked
      and nonspiked tobacco samples were used for the evaluation of the proposed
      method. Recoveries obtained were varied from 96 to 108% and RSDs from 2.0 to
      4.6%. This extraction technique was revealed to recover larger amounts of
      polyphenols from tobacco, compared to the static ultrasound-assisted extraction
      method.

PMID- 16405179
TI  - High operationally stable sol-gel diglycidyloxycalix[4]arene fiber for solid
      phase microextraction of propranolol in human urine.
AB  - A simple, sensitive, and accurate method for the determination of propranolol in
      human urine has been developed based on solid-phase microextraction (SPME)
      followed by GC-flame ionization detection (FID). The sol-gel 5,11,17,23-tetra
      tert-butyl-25,27-dihydroxy-26,28-diglycidyloxycalix[4]arene/hydroxy-terminated
      silicone oil (diglycidyloxy-C[4]/OH-TSO) fiber was prepared to accommodate to the
      harsh extraction conditions. It possesses excellent alkali-proof ability and
      retains its extraction characteristics intact even after treatment with highly
      alkaline (4 mol/L) NaOH solution. Direct chemical bonding of the coating to the
      fiber surface provides it with excellent solvent resistance and the introduction
      of calixarene enhances its thermal stability. The newly developed sol-gel
      calixarene coating was effectively used for the extraction of propranolol in
      human urine. No interference with the determination of propranolol was observed
      from the urine components. Standard curves were linear in the range 50-5000
      microg/L for headspace-SPME (HS-SPME) and 25-25000 microg/L for direct-SPME (Dir
      SPME) with correlation coefficients better than 0.9999. The detection limit was
      0.275 microg/L for HS-SPME and 0.193 microg/L for Dir-SPME. The method was
      validated using standard addition methodology and recovery values were between
      91.4 and 117% for both the sampling modes with the RSDs less than 6% at different
      concentration levels in the linear ranges. The results obtained by both the
      sampling modes were feasible, and no significant differences between them
      regarding accuracy, precision, and detection limits were seen.

PMID- 16405180
TI  - The study of enantioseparation of zolmitriptan on vancomycin-bonded chiral
      stationary phase.
AB  - In this study, the chiral stationary phase was prepared by bonding vancomycin to
      5 microm spherical silica gel according to "one-pot" synthetic strategies, and
      used to separate the enantiomers of zolmitriptan under polar ionic mode. The
      influences of mobile phase composition, such as the concentration and ratio of
      glacial acetic acid (HOAc) and triethylamine (TEA), on the enantioseparation were
      investigated, and the chiral recognition mechanism is discussed. It was found
      experimentally that the retention factors were increased with the increase of the
      HOAc/TEA concentration in a certain extent, and the ionic interactions, hydrogen
      bondings, and steric interactions may play key role together. The method is
      suitable for baseline separation of zolmitriptan enantiomers.

PMID- 16405182
TI  - Determination of 2-methylisoborneol and geosmin in aqueous samples by static
      headspace-gas chromatography-mass spectrometry with ramped inlet pressure.
AB  - A method for determining the earthy and musty odors 2-methylisoborneol (2-MIB)
      and geosmin in drinking water using static headspace-GC-MS is described. To
      achieve lower detection limits, split ratio was optimized with ramped inlet
      pressure for large headspace sampling volume. The ramped inlet pressure, which
      held higher pressure (higher column flow rate) only during injection, allowed us
      to inject 3-mL volume to GC with very low split ratio (2:1). Although sequential
      analysis with a stainless steel ion source often changed the mass spectrum of 2
      MIB, this spectral change was eliminated by using an inert ion source with a 6 mm
      drawout plate. The detection limits of this method were 0.36 and 0.14 ng/L,
      respectively, for 2-MIB and geosmin. The repeatabilities (n = 30) were 6.6 and
      4.8%, respectively, at 1 ng/L for 2-MIB and geosmin.

PMID- 16405181
TI  - Structural and temperature effects in the high-performance liquid chromatographic
      enantioseparation of 1-(alpha-aminobenzyl)-2-naphthol and 2-(alpha-aminobenzyl)-1
      naphthol analogs.
AB  - The enantiomers of 1-(alpha-aminobenzyl)-2-naphthol and 2-(alpha-aminobenzyl)-1
      naphthol analogs were separated isothermally on a cellulose-tris-3,5
      dimethylphenyl carbamate-based chiral stationary phase (Chiralcel OD-H), at 10
      degrees C increments in the range of 5-35 degrees C, using n-hexane/2
      propanol/diethylamine as mobile phase. The mobile phase composition and
      temperature were varied to achieve baseline resolutions in a single
      chromatographic run. The dependence of the natural logarithms of selectivity
      factors, In alpha, on the inverse of temperature, 1/T, was used to determine the
      thermodynamic data of the enantiomers. The thermodynamic data revealed that all
      the compounds in this study separate via the same enthalpy-driven chiral
      recognition mechanism.

PMID- 16405184
TI  - Analysis of urinary biomarkers for exposure to alkyl benzenes by isotope dilution
      gas chromatography-mass spectrometry.
AB  - A validated GC-MS method for the analysis of urinary metabolites of alkyl
      benzenes is reported. Metabolites for exposure to toluene, xylene and
      ethylbenzene were analyzed simultaneously using stable isotope substituted
      internal standards. The method entailed acidic deconjugation of urine samples
      followed by extractive alkylation with pentafluorobenzyl bromide as alkylating
      agent. The resulting pentafluorobenzyl derivatives of ortho-, meta-, para-cresol,
      mandelic acid (MA), hippuric acid (HA) and ortho-, meta-, para-methylhippuric
      acid (MHA) were then quantified by SIM. Optimized reaction conditions for the
      extractive alkylation step are reported. The derivatives were found to be
      sufficiently stable for overnight batch analysis. The LODs were below 0.1
      micromol/L for the cresols and below 1 micromol/L for MA and the HAs. Within
      batch precision for o-MHA was 7%, for m-MHA 5%, for p-MHA 5.2% and below 5% for
      the rest of the analytes.

PMID- 16405183
TI  - Methyl benzoate as a marker for the detection of mold in indoor building
      materials.
AB  - A convenient analytical method to quantify volatile organic compounds (VOCs)
      emitted from various building materials has not been addressed yet. This work
      presents a new and rapid automated method using SPME combined with GC/MS. Methyl
      benzoate - as a metabolic biomarker for mold growth-was used to indicate VOCs and
      to determine and assess mold growth on damp samples. Gypsum board and wall-board
      paper were used as examples of common indoor building materials. Optimized
      extraction conditions were carried out manually, using a GC/flame ionization
      detector. Moldy samples were analyzed using an automated SPME-GC/MS analysis
      under optimized conditions. The amount of methyl benzoate emitted from the
      studied samples ranged from 32 to 46 ppb, where the density of the fungal biomass
      was found to be 8 x 10(4) cells/mL. A relationship between the amount of fungal
      biomass and the emitted concentration of methyl benzoate was found and assessed
      based upon cultured mold samples taken from indoor building sites. The analytical
      method shows promise for the compound methyl benzoate, which can easily be
      identified at low detection limits (LOD = 3 ppb) and good linearity (>0.988), and
      its extraction and detection can be accomplished cleanly by current extraction
      techniques. Results suggest that this method with easy sample preparation can be
      used for quantitation and, of importance, minimal matrix effects are observed.

PMID- 16405185
TI  - Separation and determination of enkephalin-related peptides using capillary
      electrophoresis.
AB  - CZE with UV-absorption detection has been used for the separation and
      determination of enkephalin-related peptides. The experimental conditions, such
      as pH and concentration of running buffer, applied voltage, injection method, and
      time, were investigated in detail. Excellent separation efficiency could be
      obtained for ten enkephalin-related peptides with a 50 microm (ID) x 58 cm
      capillary using sodium dihydrogen phosphate as the running buffer (pH 3.11) when
      20 kV of applied voltage was used. The concentration detection limits were found
      to be in the range of 0.31-1.94 microg/mL (defined as S/N = 3). The proposed
      method has been applied to analyze the spiked cerebrospinal fluid (CSF) sample,
      and the results showed that CZE is a powerful technique for separation and
      detection of the above biological peptides.

PMID- 16405186
TI  - Characterization of etched electrochemical detection for electrophoresis in
      micron inner diameter capillaries.
AB  - An enhanced etched electrochemical (EC) detection technique has been developed
      for CE in micron inner diameter capillaries. The design improvements allow for
      better alignment between the capillary bore and the electrode. This new method
      involves utilizing a carbon fiber microelectrode and etching both the carbon
      fiber and the detection end of a micrometer-sized inner diameter capillary to
      limit dead volume and analyte diffusion at the amperometric EC detector. To
      understand the factors affecting enhanced detector efficiency, a detailed
      examination of the relationship between detector design and performance has been
      completed by exploring the effects of varying electrode diameter, tip shape, and
      size, in addition to the etch length of the capillary outlet. The enhanced
      detection provides peak efficiencies as high as 75000 theoretical plates and
      estimated detection limits as low as 40 nM for dopamine. This etched detection
      method should further facilitate volume-limited sample analysis by CE.

PMID- 16405187
TI  - Synthesis of monodisperse poly(chloromethylstyrene-co-divinylbenzene) beads and
      their application in separation of biopolymers.
AB  - The monodisperse, porous poly(chloromethylstyrene-co-divinylbenzene) beads of 7.9
      microm were prepared by a single-step swelling and polymerization method. The
      seed particles prepared by dispersion polymerization exhibited good absorption of
      the monomer phase. Based on this media, a weak cation-exchange (WCX) stationary
      phase for HPLC was synthesized by a new chemically modified method. The prepared
      resin has advantages of biopolymer separation, high column efficiency, low column
      backpressure, high protein mass recovery, and good resolution for proteins. The
      dynamic protein-loading capacity of the synthesized WCX packings was 18.2 mg/g.
      Five proteins were separated in 3.0 min using the synthesized WCX stationary
      phase. The experimental results show that the obtained WCX resin has very weak
      hydrophobicity. The WCX resin was also used for the rapid separation and
      purification of lysozyme from egg white in 5.0 min with only one step. The purity
      and specific bioactivity of the purified lysozyme were found to be more than 93%
      and 70 245 U/mg, respectively.

PMID- 16405188
TI  - Capillary array electrophoresis for the research of asymmetric transformation
      reaction of L-proline to D-proline.
AB  - One asymmetric transformation reaction of L-proline (L-Pro) to D-proline was
      studied by a home-made capillary array electrophoresis (CAE) for the first time.
      The aldehyde catalysts and the organic acid solvents for the asymmetric
      transformation reaction were rapidly screened and the enantiomeric excess values
      of the asymmetric product of L-Pro were directly obtained from the
      electrophoretogram of CAE.

PMID- 16405189
TI  - [Towards the general theory of immunity].
AB  - The molecular studies of plant immunity resulted in revealing general pattern in
      the mechanisms of innate resistance of plants, invertebrates and vertebrates.
      These studies removed an ambiguity in the estimate of the role of different
      immunomodulators (supressors, specific and non-specific elicitors) of plant
      parasites, and allowed approaching the general theory of immunity. Such theory
      could be based on guard model of Biezen and Jones (1999), according to which the
      specific elicitors of parasites work as a factor of pathogens. Their ability to
      suppress the immune response to infection is determined by bounding of signal
      proteins of plants and stopping the transmission of signal to the factors that
      regulate transcription. Resistance proteins recognize the complex and interacting
      with it turn the cellular metabolism to the induction of defense response.

PMID- 16405190
TI  - [The role of historical processes in determining tree species richness in the
      forests of Western Caucasus].
AB  - To estimate the role of history in variation of tree species richness in the
      forests of the Western Caucasus we analyzed correlation between their local
      richness (S--the mean number of species per 300 m2) and size of actual species
      pool (N--the number of species per 1 ha). If compared communities are differently
      distant from the point of evolutionary equilibrium one should expect a
      significant variation in correlation between S and N (determined with the greater
      sensitivity of N than S in respect of historical factors). The lower value of N/S
      corresponds to less saturated level of historically determined species richness.
      A mean N/S ratio in Japana temperate broadleaved forests (Masaki et al., 1999)
      provided the basis for analysis. The present tree species richness of the forest
      communities in the 1 ha plots seem essentially determined by the historical
      processes. The mountain forest communities of Western Caucasus are characterized
      on the average with lower saturation level of the actual tree species pool in
      comparison with the Japan temperate broad-leaved forest communities. On the
      Western Caucasus the middle mountain beech and coniferous-broadleaved communities
      (400-1600 m a.s.l.) are characterized with the higher saturation level of the
      actual species pool in comparison with communities located lower and higher.
      These results confirm published historical reconstructions, according to which
      the middle mountain forest communities in the Western Caucasus are older than
      forests located higher or lower. Present low mountain forests of the southern (to
      Black Sea) and the northern macroslopes of the Western Caucasus are characterized
      with similar saturation level of the actual species pool. These data agree with
      the assumption of Dolukhanov (1980) that low mountain zone of the southern
      macroslope was not a refuge for tree species in Pleistocene.

PMID- 16405191
TI  - [The seasonal variability of Drosophila population according to the individual
      asymmetry].
AB  - The natural Drosophila population is characterized by the presence of directional
      (DA) and fluctuating (FA) asymmetry of individuals. It was found that genotype
      has an effect on DA-level. FA evaluated in spring, summer and autumn periods had
      its maximum value in summer period. Genetically determined seasonal decrease in
      size of individuals was accompanied with increase in their FA. The structure of
      FA population variability is defined by genotypes of individuals. The phenotype
      and genotype structures of Drosophila population were investigated by FA of the
      individuals. There was regrouping of lineages number within of each frequency
      class in period from spring to autumn. Investigating central frequency class with
      least FA values in spring to summer period we observed the decrease in number of
      lineages for all traits with the exception of sternoupleral bristles (SB). At the
      same time the increase in number of lineages in the central and extreme frequency
      class with maximal FA values of sternoupleral bristles (SB). At the same time the
      increase in number of lineages in the central and extreme frequency class with
      maximal FA values of lines is observed. The number of lineages in the central
      frequency class of genotype structure is prevailing to all traits, without
      dependence on season. Individuals with rather high FA value acquire advantages in
      summer period whereas the individuals with low FA--in spring and autumn periods.
      Annual dynamics of FA is defined by this population parameters reorganization.
      The reasons of seasonal change of FA are discussed.

PMID- 16405192
TI  - [On the impact of winter conditions on the dynamics of a population with non
      overlapping generations: a model approach].
AB  - The authors propose new type of models with non-overlapping generations. It is
      assumed that during winter period individuals are not active (as, for example, in
      insect populations in boreal forests) and some portion of population dyes.
      However the portion of population, that survives, Q, indirectly depends on
      feeding conditions in previous growing season. In the formal terms, Q = Q(u) is a
      decreasing function of the mean population size u (i.e., of the integral) over
      the growing period, and traditional discrete-time model therefore turns into a
      discrete-continuous one. Under any constant birth rate Y, the model is reduced to
      a discrete one in its general form, and a general result consists in global
      stability of the zero solution for any Y < 1, e.t., in population extinction from
      any initial state. In particular cases of dependence of Q(u) and different types
      of population self-limitation during growing season the general model results in
      a great variety of discrete models (including well known Moran-Ricker and Skellam
      models). For logistic growth of population during the growing season and
      exponential decrease in Q(u), the condition is obtained for a non-trivial steady
      state to exist, and the outcome is presented for bifurcation analysis with regard
      to parameter Y: cycles with typical period-doubling and chaotic dynamics.

PMID- 16405193
TI  - [Longitude variability of macrobenthos in the streams of Central European
      Russia].
AB  - The changes in macrobenthos community depended on changes in stream discharge
      (from 0.001 m3/sec to 100 m3/sec) were studied on the basis of data from 254
      stations of 180 streams located in the centre of European part of Russia. While
      discharge of stream increases community composition changes considerably. Species
      diversity increases from 12 to 47 species per station with the increase in stream
      size. Moreover, the diversity of almost all groups, discerned according habitat
      or trophic position and main taxonomic groups (with the exception of Plecoptera
      and Diptera) increases with the increase in stream discharge. The diversity of
      lithorheophilic species and species inhabiting soft substrates is higher in small
      streams, whereas phitophilic species are more diverse in large streams. With the
      increase in stream size the percent of algophagous and filter feeders increases,
      percent of carnivorous remains the same and the percent of detritophages
      decreases. The relative role of invertebrates macrotaxons change with the stream
      size: in the smallest streams the diversity is the highest among Diptera,
      Trichoptera and Plecoptera, in medium-size streams--among Trichoptera,
      Ephemeroptera and Diptera, in large streams--in Ephemeroptera, Gastropoda and
      Trichoptera. In some groups some species replace other (close-related) in
      parallel with change in stream discharge however in general this tendency is
      weak. The index of saprobic conditions increases with the increase in stream size
      from 1.6-1.7 to 2.3-2.4. In small streams the saprobic conditions are very
      different whereas large streams have tendency to be at beta-mesosaprobic level.
      Cluster analysis reveal four size classes of streams. Peculiarities of habitat
      and macrobenthos fauna of these classes are described.

PMID- 16405194
TI  - [Symmetries and homologies of Geomerida].
AB  - The symmetry of Earths life cover (Geomerida) was described generally by L.A.
      Zenkevich (1948). It coincides with the symmetry of geographic cover. Its
      symmetry elements are equatorial plane and three meridonal planes corresponded to
      oceans and continents. The hypsographic curve with point of inflection (symmetry
      element) on 3 km depth line should be added to these elements. The plankton and
      benthos communities as well as fauna of taxons are distributed symmetrically
      according these symmetry elements. Zenkevich model was successfully extrapolated
      to plankton by K.V. Beklemishev (1967, 1969) and to abyssal benthos by Sokolova
      M.N. (1986). The plankton communities inhabiting symmetrically located
      macrocirculations are considered as homologous. The character of circulation
      determines the trophic structure of plankton and benthos. In the case of high
      productivity of plankton, benthic grazing animals feed on sedimented particles
      have bilateral symmetric mouthpart. Otherwise they have to acquire food from
      water column and use cyclomeric mouthpart. Thus, the symmetry of
      macrocirculations determines the symmetry distribution of benthic animals with
      two major symmetries of mouthparts. The peculiarities of organisms' symmetry are
      discussed in the context of Pierre Curie principle and the ideas of K.V.
      Beklemishev concerning evolution of morphological axes.

PMID- 16405195
TI  - [The problem of continuum versus discreteness in current ecology].
AB  - The problem of continuality versus discreteness of vegetation cover ("biocoenotic
      cover"--more generally) was the object of heated debates for at least hundred
      years. The ideas of continuality have been spread in the USSR in the 1970-80s but
      later the adherents of other approach, that focused on the discreteness of
      vegetation became more active. The author discussed the views of one of them,
      A.I. Kafanov (2005), published recently in "Zhurnal Obshchei Biologii". It is
      claimed that pluralistic approach that is characteristic for present ecology
      makes unnecessary the search for universal law of relationship between continuum
      and discreteness of biocoenotic cover. This relationship depends on the
      particular character of biocoenotic cover and the scale of study.

PMID- 16405196
TI  - Who takes a statin?

PMID- 16405197
TI  - Tissue angiotensin-converting enzyme inhibitors: are they more effective than
      serum angiotensin-converting enzyme inhibitors?
AB  - Since their discovery in the 1980s, angiotensin-converting enzyme (ACE)
      inhibitors have been shown to decrease angiotensin formation, prevent breakdown
      of bradykinin, and may also act on peptides of the renin-angiotensin system. They
      are effective in reducing the risk of heart failure, myocardial infarction, and
      death from cardiovascular causes in patients with left ventricular systolic
      dysfunction or heart failure, and have been shown to reduce atherosclerotic
      complications in patients who have vascular disease without heart failure. They
      may preserve endothelial function and counteract initiation and progression of
      atherosclerosis. Broadly, ACE inhibitors can be divided into tissue specific or
      serum ACE inhibitors. Tissue-specific ACE inhibitors as a group are not superior
      to serum ACE inhibitors in the treatment of coronary artery disease. Pending
      direct comparator clinical trials between a tissue ACE inhibitor and a plasma ACE
      inhibitor, both ramipril and perindopril can be recommended for secondary risk
      prevention, based on the evidence.

PMID- 16405198
TI  - FilterWire distal embolic protection device for vein graft stenting: initial
      single-center experience.
AB  - BACKGROUND: Saphenous vein graft (SVG) intervention is associated with a
      significant incidence of major adverse cardiac events (MACE) related to distal
      vessel embolization. The FilterWire distal embolic protection device has recently
      been approved as an adjunct to SVG intervention. We report here our initial
      experience in a single center in 30 consecutive patients using this device in SVG
      stenting. HYPOTHESIS: This study examined the outcomes and complications
      associated with these devices, as well as whether proficiency with the devices
      increased with greater experience and whether there were measurable outcome
      differences between devices. METHODS: We retrospectively identified all patients
      in whom a FilterWire device was placed at our hospital between June 2001 and June
      2004. RESULTS: The device was successfully deployed in 29 of 30 patients, and all
      patients were stented successfully. Overall MACE rate was 6.6%, consistent with
      reports in larger multicenter clinical trials. Transient decreases in flow were
      noted while the device was in place in six patients, but improved in five
      patients with device removal. CONCLUSIONS: This early experience in a single
      center using FilterWire embolic protection indicates that excellent clinical
      results can be obtained by the adoption of filter protection for SVG
      intervention, without evidence for a detrimental learning curve.

PMID- 16405199
TI  - Evidence supporting a new rate threshold for multifocal atrial tachycardia.
AB  - BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (COPD) is
      overwhelmingly represented among patients presenting with multifocal atrial
      tachycardia (MAT) and has been used as a paradigm for such patients. The
      quasidiagnostic tachycardia threshold for MAT is conventionally set at 100
      beats/min. Nevertheless, this threshold has not been demonstrated to be optimal.
      HYPOTHESIS: Using COPD as a paradigm for MAT, clinical experience led to the
      hypothesis that MAT with a tachycardia threshold < 100 beats/min could be more
      closely associated with COPD exacerbation. METHODS AND RESULTS: We reviewed 60
      consecutive patients with multifocal atrial arrhythmia (MAA) at any heart rate
      and found a better association between the incidence of COPD exacerbations and
      MAT using a tachycardia threshold of 90 beats/min (p = 0.00036) than when using a
      threshold of 100 beats/min (p = 0.515). CONCLUSION: The rate threshold of MAT
      should be reduced from 100 to 90 beats/min.

PMID- 16405200
TI  - Thallium-201 single-photon emission computed tomography: quantitative assessment
      of left ventricular perfusion and structural change in patients with chronic
      aortic regurgitation.
AB  - BACKGROUND: Previously, perfusion defect in the left ventricle was detected by
      thallium-201 (201T1) single-photon emission computed tomography (SPECT) in aortic
      regurgitation (AR). The significance of 201T1 SPECT, however, has not been
      clarified. Limited information is available regarding the relationship between
      functional characteristics and scintigraphic findings. HYPOTHESIS: The purpose of
      this study was to elucidate the role of exercise 201T1 SPECT in assessing
      myocardial perfusion or structural change in chronic AR. We examined the
      correlation between 201T1 scintigraphic findings and left ventricular (LV)
      function parameters in 11 patients. METHODS: Defect volume ratio (DVR) in
      exercise 201T1 SPECT was used as a parameter of the range of abnormal thallium
      distribution. Left ventricular parameters were obtained by right and retrograde
      left cardiac catheterizations. The relationship between DVR and the parameters
      was analyzed. RESULTS: The DVR ranged from 1.0 to 28.3% (average 12.1 + 8.5 %).
      There was a significant correlation (r = 0.77, p < 0.05) between DVR and end
      diastolic volume index (EDVI), a definite correlation (r = 0.66, p < 0.01)
      between DVR and end-systolic volume index (ESVI), and a good correlation (r = 
      0.77, p <0.05) between DVR and end-systolic wall stress (ESS)/ ESVI; however, no
      such correlation was found between DVR and ejection fraction. CONCLUSION: All
      patients showed abnormal defects in 201T1 accumulation scattered across the
      entire ventricle. A strong correlation between DVR and ESS/ESVI, an index of
      myocardial contractility, was a major finding of this study, suggesting a
      significant association between abnormal myocardial perfusion or structural
      alteration and reduction in myocardial contractility in chronic AR.

PMID- 16405202
TI  - Increase in aortic pulse wave velocity is associated with abnormal postprandial
      triglyceride response.
AB  - BACKGROUND: Aortic pulse wave velocity (aPWV), an index of aortic distensibility,
      and postprandial hypertriglyceridemia are recognized as independent
      cardiovascular risk factors. HYPOTHESIS: The aim of this study was to evaluate
      the relationship between postprandial hypertriglyceridemia and changes in aPWV.
      METHODS: We prospectively studied 45 patients (mean age 48 [14] years, 28.9%
      men), who were submitted to a standardized fat meal (FM) test. According to their
      triglyceride (TG) levels 2, 4, 6, and 8 h after the FM, the patients were divided
      into two groups: Group 1 (31 patients) with postprandial TG levels < or = 219
      mg/dl, and Group 2 (14 patients) with TG levels > 219 mg/dl at one of the
      aforementioned time intervals. Before and 6 h after the FM, aPWV was measured
      noninvasively. RESULTS: Baseline characteristics in the two groups were similar,
      except for higher TG, pulse pressure, waist-to-hip ratio, percentage of patients
      who smoked or had arterial hypertension, and lower high-density lipoprotein
      cholesterol levels in Group 2. Postprandially, aPWV was higher in Group 2
      [11.2(2.7) vs. 9.1(2.1) m/s, p = 0.004]. Changes in aPWV correlated with TG
      changes from baseline to 6 h after FM (r = 0.539, p < 0.001) and with the areas
      under the TG curve (r = 0.617, p < 0.001). A postprandial TG increase of 100
      mg/dl resulted in a 0.88 m/s rise of aPWV. CONCLUSION: An increase in aPWV 6 h
      after an FM test correlates positively with abnormal postprandial
      hypertriglyceridemia. These relationships, reported here for the first time,
      could be of practical use for better evaluation of patient prognosis.

PMID- 16405201
TI  - Markers of inflammation in acute coronary syndromes: association with increased
      heart rate and reductions in heart rate variability.
AB  - BACKGROUND: Systemic and vascular inflammation is at the heart of the thrombotic
      occlusion of coronary arteries. HYPOTHESIS: The study was undertaken to determine
      the relationship between established inflammatory markers (interleukin-6 [IL-6]
      and high-sensitivity C-reactive protein [hs-CRP]), neutrophil or white cell
      count, and concomitant autonomic tone in patients with coronary artery disease
      soon after occlusive events. METHODS: We tested the linkage between autonomic
      tone (as defined using both time domain and frequency domain estimates of heart
      rate variability [HRV]) and circulating markers of inflammation (white cell
      counts, hs-CRP, and IL-6) in a sample of 100 patients with proven acute coronary
      syndrome and compared these with healthy controls (n = 49) and the relationships
      on repeated measures at 4 months in recovery (n = 51). RESULTS: We demonstrated
      predictable depressed HRV in acute patients who tended to show recovery by 4
      months. The acute changes in HRV indices (e.g., triangular index) showed modest
      negative correlation (r = -0.2-0.3) with the acute elevation of white cell count,
      IL-6, and hs-CRP. These associations did not persist on multivariate analysis of
      data gathered at 4 months post event. CONCLUSION: These observational data, while
      limited, are the first to link autonomic tone and in particular sympathetic tone
      (as indicated by HRV), to the process of acute leukocytosis and systemic
      inflammation common in acute coronary syndromes.

PMID- 16405204
TI  - John W. Kirklin (1917-2004).

PMID- 16405203
TI  - Images in cardiology: Transient left ventricular apical ballooning syndrome.

PMID- 16405205
TI  - Why the big deal about research partnerships?

PMID- 16405206
TI  - Predictors of symptom distress in women with breast cancer during the first
      chemotherapy cycle.
AB  - PURPOSE: To determine the extent to which personal characteristics and "person
      factors" predict symptom distress during the first cycle of chemotherapy. DESIGN:
      Prospective, longitudinal, correlational. SAMPLE AND SETTING: 120 women with
      Stage I and II breast cancer starting their first cycle of chemotherapy were
      recruited from six diverse oncology settings. METHODS: Self-report questionnaires
      were completed prior to the beginning, the nadir, and the end of the first
      chemotherapy cycles. MAIN RESEARCH VARIABLES: Personal characteristics, "person
      factors", and symptom distress. FINDINGS: Optimism and external locus of control
      predicted low symptom distress levels at the both the nadir and at the end of the
      first cycle. Fatigue, appearance, and insomnia caused the greatest distress with
      higher symptom distress scores reported at the nadir with a mean item score of
      1.98 on a five-point Likert scale. CONCLUSIONS: Women who maintained a positive
      outlook, and trusted their health care providers experienced lower levels of
      symptom distress. Findings suggest that most women experienced some symptom
      distress, particularly during the middle of the first cycle of chemotherapy.

PMID- 16405207
TI  - Needs of patients living with advanced disease.
AB  - When a person has a life-threatening illness, many changes occur. These changes
      are more than just physical changes and include psychosocial, practical and
      spiritual consequences. If disease progresses, the impact of these changes
      intensifies. Nurses who are caring for patients with advancing disease must be
      able to provide appropriate interventions if they are to help individuals cope.
      This paper highlights information regarding the needs of patients with advanced
      disease and emphasizes approaches that could be taken by cancer nurses in their
      care of these patients. The material is drawn from over a decade of interviewing
      patients about their experiences with cancer, the literature about patient needs,
      and discussions with care providers. The over-arching perspective is one of
      seeing human beings as bio-psychosocial-spiritual entities. Holding this
      perspective has implications for assessment and interventions in caring for
      patients with advanced disease.

PMID- 16405208
TI  - A research course to promote evidence-based nursing practice.
AB  - Evidence-based practice (EBP) enhances the care of patients and families by
      guiding nurses in their patient care. Nursing leaders, health care administrators
      and policymakers are increasingly requiring that nursing practice be based on the
      best available evidence. Murdoch (2004) stated that a review and synthesis of
      existing research is essential to identify the best available evidence. Koop
      (2002) further reflected on the challenges faced by oncology nurses when there
      are clinical situations for which there is little or no empirical evidence on
      which to base nursing decisions. A need to learn skills and gain confidence in
      identifying the best available evidence frequently motivates staff nurses and
      clinicians to learn more about critical appraisal of the research literature. At
      the McGill University Health Centre (MUHC), these needs have prompted nurses to
      enrol in the research utilization (RU) course that the health centre offers. This
      column will outline the context and components of the RU course and summarize
      feedback from participants. Challenges and limitations of this strategy and its
      relationship to oncology nursing practice are highlighted.

PMID- 16405209
TI  - Refinement of a questionnaire to assess individuals' patterns of health
      information-seeking behaviour.

PMID- 16405210
TI  - A new look at core gender and gender role identity in women.

PMID- 16405211
TI  - Premodern, modern, and postmodern perspectives on sex and gender mixes.
AB  - Postmodern sensibilities, generally associated with relational psychoanalysis,
      are applicable also in traditional and contemporary Freudian psychoanalytic
      contexts. Historically speaking, views of femininity and female sexuality may be
      ordered according to positions designated as premodern, modern, and postmodern.
      This temporal continuum provides a basis for incorporating aspects of postmodern
      feminist approaches to deconstructing gender into a more traditional yet
      contemporary psychoanalytic framework. The postmodern "crisis of category" is
      addressed through a critique from a modern psychoanalytic point of view of the
      gender stereotyping inherent in certain false binaries and either/or thinking of
      premodern psychoanalytic thinking regarding female (as well as male) sex and
      gender. The cultural changes brought about by the consciousness-raising of
      postmodern feminist and contemporary psychoanalytic thinking contribute
      significantly to evolutionary changes in the understanding of gender that are
      further internalized and represented intrapsychically. That is, sequential
      transformations in the internalization of new cultural norms influence the
      development of still more new cultural norms, so that progression in these
      identificatory markers of gender can be observed over successive generations.

PMID- 16405212
TI  - Gender in linear and nonlinear history.
AB  - In response to Helen Gediman's notion of premodern, modern, and postmodern eras
      in the study of gender, an argument is made for a non-linear approach to this
      history and for situating it in the context of other historical developments
      social, personal, intellectual, and institutional. Differences among modern and
      postmodern positions in the matter of the role of the body and of social
      construction are discussed. The impact of transgender and intersex communities
      and voices on psychoanalytic thinking is examined, as are the elements of
      intergenerational transmission of trauma on gender experience both conscious and
      unconscious.

PMID- 16405213
TI  - Gender on the modern-postmodern and classical-relational divide: untangling
      history and epistemology.
AB  - This essay considers the historical periodization and epistemology of
      psychoanalytic thinking about gender. Overlapping historically with feminism
      itself, psychoanalytic thinking about gender has two periods of efflorescence,
      the 1920s and 1930s, and the contemporary period beginning in the 1970s. Two
      divides have characterized our gender thinking, the modern-postmodern and the
      classical-relational. From the early theorizing of the 1920s and 1930s until
      around the early 1990s, most psychoanalytic thinking about gender should be
      considered modernist, as it draws on traditional views of scientific evidence and
      holds more universalistic and dichotomized conceptions of men and women. In the
      contemporary period, although postmodernism tends to be associated with
      relational psychoanalysts and modernist thinking with classical analysts, the
      divisions overlap. The author argues that considering any psychoanalytic theory
      as "premodern" is misleading: from its inception, psychoanalysis formed part of
      modernism.

PMID- 16405214
TI  - A new look at core gender and gender role identity in women: commentary.

PMID- 16405216
TI  - The changing language of female development. Panel report.

PMID- 16405215
TI  - Transforming feminine categories: genealogies of virginity and sainthood.
AB  - The categories of virginity and sainthood, often used as norms of femininity, are
      historically and contextually constructed. Genealogies of these categories reveal
      definitions of female subjectivity in accordance with male desires. Traditional
      conceptions of virginity have implications for theories of female development and
      sexuality, conceptions of the psychoanalytic process, and theories of social
      symbolism. Notions of virginity as an unblemished state, the first penetration by
      a penis as an irrevocable transformation to womanhood, and defloration as a
      developmental milestone in female sexuality derive from male fantasies of female
      purity that translate into justifications for social structures of control and
      ownership. While fantasies of sainthood played significant roles in the work of
      both Sigmund and Anna Freud, their images of saints, which they did not analyze,
      were unconsciously shaped by a Victorian sensibility. Because the psychoanalytic
      legacy is androcentrically informed, analysts may be hampered in their efforts to
      treat the pathologies of perfection that continue to plague women. Contesting and
      unsettling conventional epistemological assumptions open up the categories of
      virginity and sainthood to images and representations of female autonomy and
      integrity. The critical analyses offered here contribute to theories of the
      plasticity of gender and the social construction of femininity.

PMID- 16405217
TI  - A developmental perspective on the ideal of reason in American constitutional
      law.
AB  - The ideal of reason is central to contemporary accounts of citizenship in
      American constitutional law. The individual capacity for reasoned choice lies
      closely aligned with the constitutional values of personal liberty and democratic
      self-government as they have evolved in Supreme Court decisions over the past
      century. Yet as presently conceived, the ideal of reason in constitutional law
      overlooks the process by which individuals actually acquire the capacity to
      choose their own values and commitments or to engage in reasoned thinking about
      collective ends. This paper argues that we cannot hope to sustain and foster a
      constitutional polity committed to the principles of individual liberty and
      democratic self-government without knowing something about how individual
      citizens come to possess this requisite skill of mind. A developmental
      perspective on reason in constitutional law provides a framework for examining
      the source and contours of the psychological skills that make it possible to lead
      an autonomous, self-directed life and to participate meaningfully in the
      processes of democratic self-government. Developmental psychology, together with
      research in related fields, provides empirical support for the proposition that
      the psychological capacity for reasoned thinking has its roots in the early
      caregiving relationship. Thus, a comprehensive and integrated constitutional
      family law must recognize the role of early caregiving in the political
      socialization of children. This developmental approach offers a substantial
      reworking of constitutional doctrine in the areas of family privacy, parental
      rights, congressional power, and affirmative welfare rights.

PMID- 16405218
TI  - The dreamer's use of space.
AB  - The dreamer often portrays wishes, conflicts, or current problems in terms of
      visual-spatial representations and metaphors. The spatial dimensions of dreams
      frequently signify important affective themes of the dream. In doing so, they
      serve to continue or reflect processes of self-recognition in relation to the
      environment, processes that began in early childhood, when the developing child's
      experience of movement through space played a central role in organizing affect
      and motivation systems that contribute to emerging schemata of the self.
      Representations of that movement through space gradually grow to serve a broader
      symbolic function, as may be seen in the spatial dimensions of both play and
      dreaming. Spatial relations then become building blocks for aspects of metaphoric
      and abstract thinking. The resultant personal "geography," a constellation of
      physical imagery of a body moving through space, retains an important place in
      mental life as development unfolds. It is complemented and enhanced by the
      achievement of language, but it never recedes as a core aspect of self.
      Developmental and neurobiological observations suggest the clinical usefulness of
      heightened attention to this spatial aspect of dreams. Clinical examples
      illustrate how attention to the spatial arrangements of a dream and the dreamer's
      movement through space can enhance access to the affective tone and meaning of
      the dream.

PMID- 16405219
TI  - When the analyst dies: dealing with the aftermath.
AB  - The body of literature on the theme of illness and death among analysts is
      surprisingly small, considering the frequency with which patients experience such
      incidents during an analysis, and the amount of suffering and/or iatrogenic
      injury that may ensue. In the bulk of this literature patients' experiences of
      losing an analyst are treated in a descriptive way, mostly through personal
      reports. To move clinical thinking about this topic somewhat further, the
      implications for the patient when the analysis is interrupted are explored; in
      particular, a distinction is made between the loss of the person of the analyst
      as an incident on the reality level that needs to be mourned as such, and losing
      the analysis, the unique form of dialogue implied by the principle of free
      association. Consequences of the loss of this dialogue are analyzed with regard
      to the challenges it poses for clinicians called on to deal with the aftermath.
      Preventive measures within the analytic work can soften the impact of potential
      loss, as can the contribution of analytic institutions to dealing with the
      ensuing problems.

PMID- 16405220
TI  - As the wheel turns: a centennial reflection on Freud's Three Essays on the Theory
      of Sexuality.
AB  - Freud's theories of psychosexual development, while highly original, were
      anchored in the explosion of scientific studies of sex in the nineteenth century.
      Most of these studies were based on masturbation, homosexuality, and deviance,
      with little attention given to normal sexuality. Around the turn of the century,
      the narrow interest in pathological sexuality and sexual physiology gradually
      gave way to a broader interest in normal sexuality. It was in the context of
      these expanding studies of sexuality that Freud proposed the first psychological
      view of sexuality, a theory that defined sex as being at the interface between
      soma and psyche. Libido theory, which Freud developed, is a theory of drives and
      conflicts. For Freud, libido was the major force in personality development, and
      he posited sexual conflicts as the heart of neuroses, sexual fixations as the
      essence of perversions. This article traces the way Freud's libido theory has
      served as one of the mainsprings in the development of psychoanalytic theory. It
      also addresses the major revisions that have taken place in libido theory, with a
      focus primarily on object relations theory, and the impact of culture on the way
      sex and sexual mores are parsed.

PMID- 16405221
TI  - Bridging cultures or withering on the vine.

PMID- 16405222
TI  - Responses of hospital utilization review staff to reimbursement denials.
AB  - Utilization review (UR) is a strategy used by the managed care industry to
      monitor and control utilization of health care resources. The concurrent UR
      process requires that hospital staff report clinical information to payers, who
      either certify or deny reimbursement. Conflicts may arise when hospital staff
      disagree with denial decisions. The authors analyzed the various responses of a
      medical center UR staff to payer denials and found that although denials were not
      frequent, they were perceived negatively by hospital staff. Improving and
      standardizing communication among providers, payers, and patients is one means of
      reducing conflict and frustration in the event of reimbursement denial.

PMID- 16405223
TI  - Effective use of antibiotics in managed care.

PMID- 16405225
TI  - Perspective and pharmacoeconomic analyses.

PMID- 16405224
TI  - Appropriate antibiotic therapy for community-acquired respiratory tract
      infections.
AB  - Respiratory tract infections (RTIs) are expensive for MCOs and cause significant
      morbidity among their members. Although awareness of resistance to antibiotics is
      increasing, antibiotic selection for community-acquired RTIs remains largely
      empiric. When making formulary decisions, Pharmacy and Therapeutics Committees
      may want to consider the spectrum of coverage that an antibiotic provides and its
      vulnerability to resistance development. Through appropriate formulary management
      and provider education, MCOs can promote successful clinical and economic
      outcomes. This article examines the current status of antibiotic therapy for
      community-acquired RTIs and encourages the incorporation of new parameters into
      MCO formulary decision processes.

PMID- 16405227
TI  - [Study of the functions of sleep].
AB  - Sleep is present in all species where it has been studied, but its functions
      remain unknown. To investigate what benefits sleep may bring, many aproaches and
      theories exist; some of them are presented in this paper (restorative,
      protective, energy consevation, evolutionary, sleep deprivation, and selective
      sleep deprivation, protein synthesis, neural plasticity).

PMID- 16405226
TI  - Making the most of managed care dollars spent for postmenopausal osteoporosis.
AB  - To maximize the limited resources available for osteoporosis care, MCOs need
      medication treatment criteria focusing on elderly women (> or = 65 yr) who have
      suffered fractures. Programs that identify high-risk individuals encourage long
      term medication adherence, and track outcomes to ensure efficient resource use.
      Avoiding drug therapy in low-risk patients and assuring high-risk patients
      receive and adhere to treatment leads to appropriate spending. Expenditure on
      provider education, system development, and osteoporosis medications saves costs
      through averting fracture care costs and can reduce the likelihood of conflicts
      over prescription approval, enhance osteoporosis quality scores, and improve
      patient satisfaction with their health care providers and MCOs. The objectives of
      this paper are to explain the new paradigm for osteoporosis drug therapy, and to
      encourage managed health organizations to implement programs that can improve the
      quality of osteoporosis care while achieving cost savings.

PMID- 16405228
TI  - [Methods for the quantification of left ventricular volumes assessed by
      radionuclide ventriculography (first part)].
AB  - The purpose of this study was to point out the existing methods and to describe
      and evaluate the accuracy of new, original, "Geometric-count-based" (GCB) method,
      based on radionuclide ventriculography, for the measurement of left ventricular
      volumes compaired to the contrast ventriculography. By having done this, the aim
      was to compare the accuracy of GCB method and other two radionuclide methods
      available for left ventricular volume measurements: Count-bases Massardo method
      and gated blood pool SPECT method. In GCB method count based data from
      radionuclide ventriculography were combined with geometric ones assuming a
      prolate ellipsoid left ventricular's shape with identical short axes. The
      following equation for computing left ventricular end-diastolic volume was
      developed: EDV = 2 x c x M x C(tot)/C(max), (1) where: 2c--manually drown short
      axis of prolate ellipsoid (left ventricle) at end-diastolic frame, M-calibrated
      pixel size, C(tot)--total counts in left ventricular's region of interest at end
      diastolic frame, C(max)--maximum pixel counts in left ventricular's region of
      interest. Physical experiments with two different heart shaped phantoms were used
      to compare volumes assessed by all three radionuclide methods with the true
      volumes. The true volumes of cylindrical and ellipsoid phantoms of 112.5 ml and
      190.5 ml, were computed to be 114 ml and 196 ml by our GCB method, 168 ml and 180
      ml by Massardo method and 142 ml and 222 ml by gated blood pool SPECT methods,
      respectively. In clinical study, in 65 patients volumes assessed by radionuclide
      methods were compared to volumes measured using single plane contrast
      ventriculography as a gold standard. A good correlation of our original method
      was obtained with a contrast ventriculography for both EDV/m2 and ESV/m2 (r =
      0.94, r = 0.92), slightly lower for Massardo method (EDV/m2: r = 0.90, ESV/m2 : r
      = 0.89) and significantly lower for gated blood pool SPECT (EDV/m2: r = 0.85,
      ESV/m2: r = 0.81, p < 0.01). In conclusion, both, phantom and clinical studies
      indicate that GCB radionuclide method is accurate, noninvasive for left
      ventricular volumes' measurement and should be widely used in everyday clinical
      practice.

PMID- 16405229
TI  - [Radionuclide ventriculography in evaluation of cardiac function in valvular
      diseases (second part)].
AB  - Patients with valvular heart disease usually require serial, long-term evaluation
      to determine changes in the severity of their disorder, its effect on ventricular
      function, and the advisability of corrective surgery. Echocardiography is
      excellent technique for visualization of the motion of atrioventricular valves,
      but it is not reliable method for quantifying valvular insufficiency. Equilibrium
      radionuclide ventriculography is readily available, noninvasive means for
      quantifying the degree of valvular insufficiency, using left to right ventricular
      stroke volume ratio. Besides, other parameters important for cardiac function,
      such as ventricular volumes and ejecton fraction can also be calculated. In this
      paper the methodology of equilibrium radionuclide ventriculography and its
      application to the functional and prognostic characterisation of patients with
      valvular diseases will be discussed.

PMID- 16405230
TI  - [Helicobacter pylori--clinical manifestations, diagnosis and therapy].
AB  - During the past 20 years the role of Helicobacter pylori have been topic of
      intensive research. Studies have established that H. pylori can cause acute and
      chronic gastritis, duodenitis, gastric peptic ulcers and duodenal ulcers non
      ulcer dyspepsia and Weird diseases and syndroms. H. pylori has been identified as
      a risk factor for gastric cancer and MALT-lymphoma. Nearly more than 90% of
      patients with duodenal ulcus, more than 70% of those with gastric ulcer and more
      than 80% patients with the gastric cancer have H. pylori infection. The discovery
      of the infective nature of peptic diseases and involvement of of H. pylori in
      theirs aetiology has begin to change our views on haw to approach diagnosis and
      therapeutic treatment in the practice. For this aim have been developed several
      methods which can be used to diagnose of H. pylori: invasive as endoscopy and non
      invasive such as urea-breath-test, detection of antigens in stool, detection of
      specific antibodies in patients sera by means of serological tests--ELISA and
      Immunblott, molecular tests PCR and fluorescence-in situ- hybridisation for the
      detection of H. pylori and its resistance for clarithromycine and metronidazole.
      There are several effective treatments which can cure gastric and duodenal ulcers
      as well as prevent theirs recurrences.

PMID- 16405231
TI  - [Scintigraphic diagnosis of inflammation and infection].
AB  - Nuclear medicine, diagnostic and therapeutic application of open sources of
      ionizing radiation in medicine, has wide range of possibilities for non-invasive
      infection and inflammation detection. The broad spectrum of methods, some of
      which are already in routine use while the others are still in the phase of
      investigation, improvement, or clinical trials, is presented. Most of the methods
      in routine use are capable of detection and localisation of both inflammation and
      infection. Antibiotic and antimicrobe peptides labelings have the possibility to
      diagnose infection and to differentiate it from inflammation, which is not the
      case with other scintigraphic methods. Availability of the radiopharmaceuticals
      and nuclear-medicine equipment, radiation exposure of the patient, clinical
      situation, the baseline pathophysiology of a process, and costs are the factors
      which contribute to the choice of the diagnostic approach. In order to ease the
      choice of the appropriate diagnostic method for inflammation/infection detection
      in different clinical situations, the recommendations from the ISORBE
      (International Society of Radiolabelled Blood Elements) are quoted.

PMID- 16405232
TI  - [Radionuclide detection of Helicobacter pylori infection].
AB  - The aim is the assessment of the HP infection in stomach using breath test and
      comparison to other diagnostic methods, as well as following up the effect of
      therapy. In 83 patients with digestive discomfort rapid urease test, histology
      and breath test were performed, while in 25 patients with proven HP infection the
      effect of therapy was followed up using breath test and clinical findings. For
      rapid urease test and histology, samples were taken from antral mucosa. Breath
      test was performed after per oral administration of the capsule of 14C- urea (37
      kBq) (Izotop, Hungary and Laboratory for radioactive isotopes, Vinca) which, in
      the presence of Helicobacter pylori breaks up to 14CO2 and NH3. Radioactivity was
      measured by beta counter in the exhaled air fasting and 30 minutes after
      ingestion of the capsule. According to our results, the rise of activity over
      100% was considered positive. From 83 patients, 58 were breath test was positive,
      24 negative and one equivocal. Fast urease test was in 54 positive, in 29
      negative while histology was in 57 postitive and 26 negative. Findings of the
      breath and urease tests were in accordance in 93% patients while breath test and
      histology in 98% patients. During follow up of the therapeutic effects, breath
      test and clinical findings were in accordance in 98% patients. Breath test can be
      useful in diagnosis but is a method of choice in following up the patients after
      therapy for H. pylori infection, because it is non-invasive, fast and precise.

PMID- 16405233
TI  - [Implementation of the radiolabelled antibiotic in the detection of orthopedic
      infections].
AB  - The aim of the study is detection and evaluation of the orthopedic infections
      using 99mTc-ciprofloxacin, radiopharmaceutical supposed to distinguish
      inflammation from infection. There were 15 true positive findings, 9 true
      negative, and two were false positive, while 1 was false negative. Sensitivity
      was 94%, specificity 82%, positive predictive value 88%, negative predictive
      value 90% and accuracy 89%. According to our results, scintigraphy with 99mTc
      ciprofloxacin is a useful method for detection and assessment of exact
      localization of orthopedic infections, which might be useful for (differential)
      diagnosis, surgical treatment in due time as well as monitoring of the treatment
      of conservative therapy.

PMID- 16405234
TI  - [Initial 111In-platelet kinetics: indicator of platelet sequestration/destruction
      site or quality control of platelet labelling?].
AB  - Taking into consideration the existing disagreement in the literature, the aim of
      this paper was to estimate the value of the initial kinetics of autologous
      platelets labelled with 111In-oxinate, performed during the first 20 minutes
      after their intravenous injection. Two hypothesis were tested: 1. Initial 111In
      platelet kinetics indicates the platelet sequestration site (in patients with
      normal mean platelet life span)/destruction site (in patients with shortened mean
      platelet life span), 2. Initial 111In-platelet kinetics indicates the quality of
      platelet separation and labelling procedure. We performed initial labelled
      platelet kinetics in thrombocytopenic patients (in order to test the first
      hypothesis) as well as in control (healthy) subjects (in order to test the second
      hypothesis). Thirty-nine persons were investigated: 33 with thrombocytopenia: 25
      with shortened mean platelet life span, caused by chronic im mune
      thrombocytopenic purpura (ITP), eight with normal platelet life span and
      thrombocytopenia caused by myelodysplastic syndrome (MDS), six healthy, control
      subjects (C). In all 39 persons platelet blood count on the day of platelet
      labelling was determined, autologous platelet labelling with 111In-oxinate was
      performed, general and differential yields of platelet labelling (GYL and DYL),
      as well as mean labelled platelets life span were determined. Besides that,
      initial labelled platelets kinetics was performed with initial 111In-platelets
      accumulation in the liver (IPAL) calculation, as well as the late platelet
      kinetics for platelet sequestration index and platelet sequestration/destruction
      site determination. We obtained two types of initial labelled platelets kinetics
      (not only in the patients with shortened platelet life span, but also in the
      subjects with normal labelled platelets life span), which differed in the IPAL
      value and in the ratio of the liver and the heart radioactivity: IPAL < 20% and
      IPAL>20%. We found statistically significant difference in GYL and DYL between
      the two groups: IPAL<20% and IPAL > 20%. Both yields were higher in IPAL<20%
      group. There was no significant difference between the two IPAL groups in the
      platelet blood count, labelled platelet life span, sequestration index and
      sequestration site. No correlation could be found between IPAL on one side and
      platelet blood count, sequestration index, and sequestration site on another. We
      concluded that initial labelled platelet kinetics could not indicate the platelet
      sequestration/destructon site (which is accomplished by the late labelled
      platelets kinetics), but nevertheless, it is very sensitive and useful method of
      platelet separation and labelling quality control. While in vitro quality control
      parameters (GYL and DYL) indicate the quality of only one part of this procedure,
      initial labelled platelet kinetics reflects discrete platelet function
      disturbance that might happen from the moment of blood sample collection till the
      labelled platelets intravenous injection.

PMID- 16405235
TI  - [Prediction of the splenectomy efficacy in chronic immune thrombocytopenic
      purpura].
AB  - The aim of this investigation was to estimate the possibility of predicting the
      splenectomy response in patients with chronic immune thrombocytopenic purpura
      (ITP). The patients' age, sex, megakaryocytes abundance, platelet blood count,
      production, life span, sequestration/destruction site were considered as possible
      predictive factors. Thirty-four ITP patients (23 female and 11 male) aged from
      five to 83 years were investigated. Platelet blood count ranged from 4 to 106 x
      10(9)l (mean value was 43 x 10(9)/l). Megakaryocyte abundance was determined in
      19/34 ITP patients. Megakaryocytes were numerous in 11/19, present in 7/19 ITP
      patients and in one patient low megakaryocyte number was registered. In all 34
      ITP patients autologous platelet labelling with 111In-oxinate was performed and
      labelled platelets were reinjected to the ITP patients. This enabled platelet
      life span, production, sequestration index and sequestration/destruction site
      determination. Platelet life span ranged from 0,4-5 days (mean value was 1 day).
      Mean value for platelet production index was 1,1. Platelet
      sequestration/destruction site in 16 ITP patients was the spleen, and in two it
      was the liver. Mixed platelet sequestration/destruction site (the liver and the
      spleen) was registered in 7 ITP patients, while predominantly splenic
      sequestration/destruction was present in 9 ITP patients. All 34 ITP patients were
      later submitted to splenectomy, which is a therapeutic option in ITP. Splenectomy
      result was favorable in 28/34 ITP patients while it was unfavorable in 6/34
      (17,6%). Highly significant correlation was noticed between the splenectomy
      result and platelet sequestration site (p < 0.01). On the other hand, there was
      no correlation between the splenectomy result on one side, and patient's age,
      sex, megakaryocyte abundance, platelet production, life span and blood count on
      the other. Splenectomy result was favorable in all ITP patients with splenic
      sequestration/detruction of labelled platelets. It was unfavorable in ITP
      patients with hepatic sequestration of labelled platelets. In ITP patients with
      mixed platelet sequestration (hepatic and splenic) there were more unfavorable
      than favorable splenectomy results. Non-invasive method of platelet labelling and
      platelet sequestration/ /destruction site determination makes easier the
      clinicians' and ITP patients' decision for the splenectomy in the case when the
      spleen is the only sequestration site of the labelled platelets, and against the
      splenectomy, when exclusively hepatic platelet sequestration/destruction is
      registered.

PMID- 16405236
TI  - [Liver hemangioma blood pool as a function of time].
AB  - Aim of the study was to determine the time needed for establishing maximal
      labelled red blood cell concentration in hemangioma by scintigraphic
      semiquantitative blood pool estimation as a function of time. PATIENTS AND
      METHODS: Eleven patients (eight females and three males) with total number of
      fourteen liver hemangiomas have been examined. Nine of them had solitary lesions
      and remaininig two patients had two and three liver hemangiomas, respectively.
      All patients underwent blood pool scintigraphy 40, 60, 120 and 180 minutes after
      in vivo labelling of autologous red blood cells using 740 MBq of 99mTc. After
      correction for radioactive decay of 99mTc and back-ground correction blood pool
      indexes, as hemangioma/heart and liver/heart counting rate ratios, have been
      calculated. RESULTS: Mean blood pool indexes obtained 40-180 minutes after in
      vivo red blood cell labelling did not differ significantly (p > 0.05) neither in
      hemangioma (0.84-0.86) nor in liver tissue (0.55-0.58). In every acquisition time
      hemangioma blood pool index was substantialy higher than that of liver tissue (p
      < 0.01). CONCLUSION: The results of the study indicates that labelled red blood
      cells concentration reaches its plateau before 40th minute following in vivo
      labelling. The concentration difference between hemangioma and liver tissue also
      does not differ significantly after 40th minute of blood pool examination. In
      most patients blood pool scintigrams taken 60, 120 and 180 minutes following in
      vivo RBC labelling do not contribute to diagnostic value of the method.

PMID- 16405237
TI  - Pay for performance: national and local accountability for health care.

PMID- 16405238
TI  - Evidence for pay for performance: hope for the U.S. health care system?

PMID- 16405239
TI  - The JCAHO guidelines for pay for performance.

PMID- 16405240
TI  - Reports confirm high value of step-therapy programs.

PMID- 16405241
TI  - Taxpayers reject idea of losing deduction for health insurance.

PMID- 16405242
TI  - Health plan medical directors doing well.

PMID- 16405243
TI  - Consumers don't know what they don't know.

PMID- 16405244
TI  - The ethical way in a season of change.

PMID- 16405245
TI  - Flu's other cost.

PMID- 16405246
TI  - Putting EBM to work (easier said than done).

PMID- 16405247
TI  - The cost benefit to health plans of pharmacotherapy for Alzheimer's disease.
AB  - Treatment of Alzheimer's disease (AD) is a major public health issue, with the
      potential for significant impact on MCOs. As the number of people affected with
      AD continues to rise, the importance of this problem will grow as well. This
      article reviews patient and caregiver outcomes associated with reduced health
      care costs and their implications for MCOs. Cholinesterase inhibitors (ChEIs) are
      effective in treating cognitive, functional, and behavioral symptoms for patients
      with mild to moderate and moderate to severe AD. Treatment with memantine, an N
      methyl-D-aspartate (NMDA) receptor antagonist, has been shown to benefit patients
      with moderate to severe AD. Pharmacoeconomic studies indicate that donepezil and
      memantine treatment may reduce total costs of care for AD patients and their
      caregivers, with potential economic benefits to MCOs.

PMID- 16405248
TI  - Polypharmacy interventions result in sustained decreases.

PMID- 16405249
TI  - Kansas City focuses on depression.

PMID- 16405250
TI  - Pharmacy cost increases below medical for the first time in four years.

PMID- 16405251
TI  - [Mechanisms of the induction of autoimmunity].
AB  - The main function of the immune system is to protect the body by responding to
      invading microorganisms. Immunologic tolerance is the basic property of the
      immune system that provides for self/non-self discrimination so that the immune
      system can protect the host from external pathogens without reacting against
      itself. Central tolerance is achieved by the clonal deletion of self-reactive
      lymphocytes expressing receptors with high avidity for self. Autoreactive
      lymphocytes which escaped selection in the central lymphoid organs are present in
      the peripheral repertoire but but are kept under control by multiple diverse
      peripheral tolerance mechanisms acting either directly on the self-reactive T
      cell (T-cell intrinsic) or indirectly via additional cells (T-cell extrinsic).
      Intrinsic mechanisms include ignorance of autoantigens, anergy, phenotype skewing
      or activation-induced cell death of autoreactive T lymphocytes, while extrinsic
      mechanisms act through immature and/or tolerogenic dendritic cells as well as
      different types of regulatory cells. Autoimmune diseases are associated with
      humoral or cell-mediated immune reactions against one or more of the body's own
      constituents. Activation and clonal expansion of autoreactive lymhocytes is a
      crucial step in the pathogenesis of autoimmune diseases. They result from the
      complex interactions between genetic traits and environmental factors, among
      which infections are the most likely cause. Several basic mechanisms may be
      operating whereby an infectious agent actually induces apparent autoimmne
      reactivity including molecular mimicry, bystander activation, induction of
      costimulation, polyclonal activation, altered processing and expression of
      cryptic antigens. Although many questions regarding autotolerance and etiop
      athogenestis of autoimmunity have yet to be resolved, it is evident that multiple
      overlapping pathways are operative in establishing, maintaining and breaking
      autotolerance, as well as during the initiation, progression, and final effector
      phases of autoimmunity.

PMID- 16405252
TI  - [Autoimmune thyroid disease--clinical symptoms of associated autoimmunity].
AB  - Autoimmune diseases are manifested in a broad spectrum. Classic examples of organ
      specific autoimmune disease include Addison's disease, insulin-dependent type-1
      Diabetes mellitus, Grave's disease (MGB), and Hashimoto thyroiditis (HT). The
      initial report of this autoimmune thyroid disease (AITD) dates back to Hakira
      Hashimoto (1912). In HT, as an organ-specific autoimmune disease, massive
      infiltration of lymphoid cells and parenchyma destruction are a consistent
      feature. The infiltration appears to be immune-mediated, primarily lymphocytic (T
      helper, T suppressor cells), NK cells and B cells. The pathological
      characteristics of AITD include development of the goitre (atrophic form is not
      so frequent), impaired thyroid gland function (from hyperthyroidism to
      subclinical and manifested hypothyroidism) and the formation of antithyroidal
      antibodies against thyroglobulin (AbTg) and the microsomal antigen (Ab TPO).
      There is a very good correlation between the antibodies against TPO and the
      histological findings. Morbus Graves Basedow is characterized by autoimmune
      hyperthyroidism with goitre, and infiltrative orbitopathy. Autoantibodies against
      the TSH-receptor molecule on the plasma membrane of the thyroid gland follicles
      cause a nonphysiological activation and an increase of the cellular function.
      Besides this hyperthyroidal condition, an autoimmune attack against the
      retrobulbar tissue leading to endocrine orbitopathy, can be noted in about 40% of
      patients suffering from MGB.

PMID- 16405253
TI  - [Diagnosis of autoimmune thyroid disease].
AB  - Autoimmune thyroid disease (AITD) is the most common organ specific autoimmune
      disorder usually resulting in dysfunction (hyperfunction, hypofunction or both)
      of the thyroid gland. The syndromes comprising autoimmune thyroid disease are
      many intimately related illnesses: Graves' disease with goitre, hyperthyroidism
      and, in many patients, associated ophthalmopathy, Hashimoto's thyroiditis with
      goitre and euthyroidism or hypothyroidism but also thyroid dysfunction occurring
      independently of pregnancy and in 5-6% of postpartum women and thyroiditides
      induced by different drugs and other environmental influences. The immunological
      mechanisms involved in these diseases are closely related, while the phenotypes
      probably differ because of the specific type of immunological response that
      occurs. The syndromes are connected together by their similar thyroid pathology,
      similar immune mechanisms, co-occurrence in family groups, and transition from
      one clinical picture to another within the same individual over time. In some
      patients, other organ specific and nonorgan specific autoimmune syndromes are
      associated with autoimmune thyroid disease, including pernicious anemia,
      vitiligo, myasthenia gravis, primary adrenal autoimmune disease, celiac disease,
      rheumatoid arthritis or lupus. Thyroid peroxydase, TPO, the primary enzyme
      involved in thyroid hormonogenesis, was initially identified in 1959 as the
      'thyroid microsomal antigenn. It is uncertain whether TPO autoantibodies or TPO
      specific T cells are the primary cause of thyroid inflammation, which can lead,
      in some individuals, to thyroid failure and hypothyroidism. TPOAbs are the
      hallmark of AITB and are present in almost all patients with Hashimoto's
      thyroiditis, in two-thirds of patients with postpartum thyroiditis and also in
      75% of patients with Graves' hyperthyroidism. The antibodies are mainly produced
      by lymphocytic infiltrate in the thyroid gland and only to a small extent by
      regional lymph nodes or the bone marrow. Unlike antibodies against thyroglobulin
      (Tg), TPO antibodies are capable of inducing antibody-dependent cell-mediated
      cytotoxicity. Antibodies to TSH-R mimic the function of TSH, and cause disease by
      binding to the TSH-R and stimulating (or inhibiting) thyroid cells. The TSHR, a
      member of the G protein-coupled receptor family with seven membrane-spanning
      segments. Patients with autoimmune thyroid disease may have both stimulating and
      blocking antibodies in their sera, the clinical picture being the result of the
      relative potency of each species; blocking antibodies seem more common in Graves'
      patients with ophthalmopathy compared to those without this complication. The
      major T cell epitopes are heterogeneous and T cell reactivity against certain TSH
      R epitopes has been present in high proportion in normal subjects. More
      diversified response to TSH-R, with heterogeneity of epitope recognition by TSAb,
      is predictive of likely remission after antithyroid drug treatment for Graves'
      disease.

PMID- 16405254
TI  - [Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune
      disease].
AB  - Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent
      inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some
      of the up-to-date knowledge about hypothyroidism, both subclinical and
      manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland
      disease can occur at any age, but predominantly affects women after periods of
      high emotional and physical stress or accidents, as well as during periods of
      hormonal changes. It can also develop in families, and having an autoimmune
      disease slightly increases the risk of developing another. This paper showed an
      increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at
      the same time, the incidence of primary hypothyroidism accounting for 1%. It is
      very usefull to estimate the stimulated thyrotropin (TSH) response, as well as
      the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum
      level at 60th minute after TRH stimulation. Treatment of choice for HT
      (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is
      orally administered levothyroxine sodium, usually for life-time. The standard
      dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient
      dependent. Elderly patients usually require smaller replacement dose of
      levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary
      dilatator at the same time.

PMID- 16405255
TI  - [Diagnosis of osteoporosis occurring in autoimmune thyroid gland disease].
AB  - Osteoporosis or porotic bone is a general, systemic bone disease, which is
      manifested by fracture as its consequence. The main characteristic of this
      disease is the loss of bone microarchitecture, bone mass reduction, and its
      increased fragility. The result, thereof, is susceptibility to fracture. Etiology
      of osteoporosis is polymorph. Its socio-medical importance is enormous, since
      there is one osteoporotic fracture every 20 sec. worldwide. Million and six
      hundred thousand osteoporotic fractures occur annualy throughout the world.
      Thyroid gland is susceptible to autoimmune reactions that lead to autoimmune
      diseases, just like many other organs. The autoimmune disorder is a final
      consequence of a failure, in some instance, within the crucial mechanism of
      regulation of self tissue tolerance. The main goal is to prove the presence of
      osteoporosis, its inexpensive and quick diagnostics; to make a distinction among
      the causes that lead to it. In addition, to indicate the importance of
      osteoporosis that is caused by normal, metabolic processes which are an
      inevitable part of ageing. Diagnosis of osteoporosis can be done through
      laboratory, which is a tiresome, time consuming task. Measurements of BMD could
      be also performed by using new devices. Osteometers could be constructed on the
      basis of X-ray photon energy or US. Utilization most contemporary one uses laser
      beam, and it approximates the distance of additional tissue that also absorbs
      part of energy changing absorption of the reception unit and thus making the
      measurement results accurate. In diagnosing BMD by osteometer, one faces with
      certain difficulties. When axial quantitative CT is used, the value may be
      falsely lower, because of the loss of energy absorbed by aorta which is often
      calcified in elderly people. In devices with transversal scanning, of the same
      nature and technology, a part of the energy is being absorbed by transversal and
      spinal vertebrals. After the research, one may conclude that the most accurate
      results can not be achieved. But, this is not considered so important. Values
      that are to be compared are available anyway. Therapy, if adequate, will show
      certain improvement which can not be detected even by osteometers. Following the
      physiatrist treatment, particularly by exercise of muscle strength, the muscle
      structure will be enhanced and, consequently, a part of pressure will be handled,
      which would be otherwise taken over by the bone. The movements of the patients
      will be better in coordinated, which undoubtedly reduces the number of falls and
      fractures. Results of the research that was conducted at the Clinical Hospital
      Centre "Dr. Dragisa Misovic" in Belgrade, with over 200 cases, two years, are
      compatible with literature data. Working with MediTech osteometer DTU ONE that
      uses ultrasound source in demineralized medium, with indispensable US gel, on
      constant temperatures, yielded results corresponding to those in patients that
      were treated by Bisphosphonates, Alphacalcidol and Calcium therapy.

PMID- 16405256
TI  - [Dilated cardiomyopathy associated with autoimmune disease of thyroid gland].
AB  - Congestive heart failure is the main cause of cardiovascular morbidity and
      mortality with more than one million hospitalizations per year. Dilated
      cardiomyopathy is one of the main causes of congestive heart failure
      characterized by diminished function of the left, right or both ventricles and
      ejection fraction less than 40%. Numerous studies reported that the diseases of
      thyroid gland among the patients with dilated cardiomiopathy were very frequent:
      with prevalence from 18% to 49%. The impaired thyroid gland function was found as
      primary cause of cardiomyopathy in 1% of patients. At the same time, among
      patients with terminal dilated cardiomyopathy, euthyroid sick syndrome was very
      frequent with low values of T3. According to our results, 29.4% of patients with
      dilated cardiomyopathy also had autoimmunity disorder of thyroid gland with
      present antithyroglobin and antimicrosomal antibodies. These patients had lower
      ejection fraction and worse prognosis. In American College of Cardiology/American
      Heart Association guidelines for the evaluation and treatment of the congestive
      heart failure, evaluation of thyroid gland function was recommended; but the
      evaluation of antitireoglobulin antibodies and free T3 and free T4 was also
      essential, as was calculation of their ratio. This is the way to discover the
      autoimmunity disorder of thyroid gland and/ or "euthyroid sick syndrome". In
      patients with dilated cardiomyopathy and low-T3 syndrome, short-term
      administration of thyroid hormones resulted in improvement of ejection fraction,
      diminishing of symptoms and better survival.

PMID- 16405257
TI  - [Autoimmune haemopoietic disturbances simultaneous with autoimmune thyroid
      diseases].
AB  - Out of 362 patients with diagnosis of autoimmune haemopathy treated in eight-year
      period at the Hematology centre, concomitant autoimmune thyreoideopathy was
      confirmed in 22 (5.52%). The most frequent was simultaneous manifestation of
      pernicious anemia and autoimmune thyreoiditis-Phenomenon was less frequently
      observed in patients with immune thrombocytopenic purpura and Graves disease. In
      the subgroup of patients with autoimmune hemolytic anemia, there was no evidence
      of simultaneous autoimmune thyreoideopathy. General opinion is that
      etiopathogenesis of these immunological disorders does not include unique
      mechanism of humoral and cellular immune response; more probable, it is the
      question of normal immune response regulation impairment, based on the
      paerticular genetic predisposition.

PMID- 16405258
TI  - [Autoimmune thyroid disease and associated rheumatic disorders].
AB  - Musculosceletal manifestations were found in patients with hyperthyroidism as
      well as hypothyroidism. This article will review the available evidence that
      autoimmune thyroid disease is associated with: Sjogren's sydrome (SS), systemic
      lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis (RA) and
      spondyloarthropathies. Possible pathogenesis of these manifestations has not been
      completely established. Sjogren's syndrome occurs in about 1/10 of patients with
      autoimmune thyroid disease; patients with SLE and antithyroid antibodies were
      significantly older than those pattiens without antibodies. Patients with
      systemic sclerosis and thyroid disease were significantly younger than those
      without antibodies. Thyroid disfunction was found three times more often in women
      with RA than in women with noninflammatory rheumatic diseases, and those with
      thyroid disease tended to have a shorter duration of arthritis.

PMID- 16405259
TI  - [Molecular basis of glucocorticoid action].
AB  - Glucocorticoid hormones are involved in regulation of cell processes and
      coordinate physiological response to diverse signals. These hormones, through
      interaction with specific intracellular receptors, coordinate components of
      physiological repertoires by activating the expression of gene networks. Thus
      hormone-receptor complexes may function as key constituent in regulation of
      specific cell functions as well as in provoking differentiation in already
      determined cells. Analysis of steroid receptors are important for understanding
      of molecular details of transcriptional control as well as providing the insight
      as to how an individual transcriptional factor such as glucocorticoid receptor,
      contributes to cell identity and function. The purpose of this review is to
      establish the general molecular mechanism of glucocorticoid action and mechanism
      associated hormone-receptor complexes with the control of differential patterns
      (i.e. "positive" and "negative") of gene expression. One of the examples of two
      signal pathways regulating opposite gene expression are NF-kB and GR-mediated
      signal pathways. These pathways have important and opposite roles in the immune
      function. NF-kB is transcription factor which induces the expression of many
      genes that participate in immune and inflamatory response, while GR is
      transcription factor that serves as antiinflammatory agent and immune suppressor.
      Their interactions within the cell, although not yet completely understood,
      appear to be an important, possibly even the primary mechanism of immune
      homeostasis. It has not been established that glucocorticoid sensitivity can be
      caused by mechanisms other than changes of GR number and properties, although
      recent studies have indicated that receptor isoforms and transcriptional factors
      may modulate glucocorticoid responsiveness by interacting with receptor protein
      or directly at the site of DNA binding. The aim of this review is also to
      describe the role of glucocorticoid receptors in mechanism of glucocorticoid
      action on cell functions, including immune responses, as well as to present
      emerging issues on clinical aspects of molecular mechanisms of glucocorticoid
      action.

PMID- 16405260
TI  - [Therapeutic use of glucocorticoids and immunosuppressive agents].
AB  - Pharmacotherapy of autoimmune thyroid disease (AITD) is complex. Apart from the
      replacement hormone therapy, antithyroid agents, beta adrenoceptor blockers and
      other drugs, in regard to the present symptoms, it also includes the
      administration of glucocorticoids and immunosuppressive agents. Physiological
      actions of glucocorticoids are significant in number, well known and described in
      details. The most prominent pharmacological properties of glucocorticoids, that
      are important fortheir clinical use, are antiinflammatory and immunosuppressive
      actions. In this article, the most notable clinical pharmacology aspects of
      glucocorticoids have been presented, including the basic principles of their
      therapeutic use, as well as the most important indications with the examples of
      dosing regiments (rheumatic disorders, renal diseases, allergic reactions,
      bronchial asthma, gastrointestinal inflammatory diseases, thrombocytopenia, organ
      transplantation, and Graves' ophthalmopathy). In addition, adverse and toxic
      effects of glucocorticoids as well as their interactions with other drugs have
      been described. Immunosuppressive agents have important role in treatment of
      immune disorders, including the reduction of immune response in autoimmune
      diseases and organ transplantation. Apart from glucocorticoids, immunosuppressive
      agents consist of calcineurin inhibitors (cyclosporine, tacrolimus),
      antiproliferative and antimetabolic agents (sirolimus, azathioprine,
      mycophenolate mofetil, methotrexate, cyclophosphamide), monoclonal antibodies:
      anti-CD3 antibody (muromonab-CD3), anti-CD25 antibody (daclizumab), anti-TNF
      alpha antibody (infliximab). In this part, the most updated facts about mechanism
      of action, rational therapeutic use, as well as adverse and toxic effects of
      immunosuppressive agents have been reviewed.

PMID- 16405261
TI  - [Differentiated thyroid carcinoma in previously manifested autoimmune thyroid
      disease].
AB  - Autoimmune thyroid diseases are frequently associated with differentiated thyroid
      carcinomas. The role of autoimmune phenomena in the origin and clinical course of
      coexisting papillary and follicular carcinomas is still controversial. In Graves'
      patients, the prevalence of palpable thyroid nodules is 15.8%, and by using
      ultrasonography, the prevalence increases to 33.6%. Since the malignancy rate of
      palpable thyroid nodules in Graves' patients is 16.9%, approximately threefold
      higher than in general population, it seems that a thyroid nodule diagnosed in
      Graves' patients is at higher risk for malignancy. In addition, radioiodine
      therapy for Graves' disease was found to be associated with increased incidence
      of thyroid cancer in some studies. These studies however, were not able to
      confirm the carcinogenic effect of radioiodine therapy since the late growth of
      occult carcinomas could not be excluded. The frequency of the association of
      Hashimoto's thyroiditis and differentiated thyroid carcinomas is approximately
      30%. The presence of coexistent Hashimoto's thyroiditis does not affect the
      diagnostic evaluation and management of papillary thyroid cancer. The frequent
      presentation of differentiated thyroid carcinomas in Graves' disease and
      Hashimoto's thyroiditis opens the possibility that some mutual pathogenethic
      mechanisms might be involved in the development of these diseases.

PMID- 16405262
TI  - [Surgical procedures in patients with thyroid autoimmune disease].
AB  - Autoimmune thyroid disease is a serious medical problem in which various
      operative procedures are performed. The objective of the study is to explore the
      type of applied surgical procedures in autoimmune thyroid disease, advantages and
      disadvantages of various procedures, and criteria they have to meet. This is
      retrospective clinical study on 1478 patients, operated for Graves' toxic goiter
      (117 males and 795 females mean age 37.7) and Hashimoto thyroiditis (27 males and
      539 females mean age 50.6) from 1995 to April 2005. Cancer in Graves' disease was
      found in 61 patients (6.7%), papillary in 60 (occult in 53 or 6.6%) and
      metastatic in 1, Hashimoto thyroiditis and thyroid cancer was found in 141
      patients (24.9%), papillary in 116 or 20.5% (occult in 55 or 9.7%), follicular in
      2 (0.3%), Hurthle in 11 (1.9%), medullary in 8 (1.4%), anaplastic in 2 (0.3%) and
      lymphoma in 3 (0.5%). We performed subtotal bilateral lobectomy in 344 (312 in
      Graves and 32 in Hashimoto), total lobectomy on one side with subtotal on the
      oposite in 307 (228 in Graves and 79 in Hashimoto); out of them, in 59 patients,
      the remnant was left in the region of the upper pole which we called atypic
      lobectomy. The most common procedure, total or near by total thyroidectomy,
      performed in 719 (371 in Graves and 349 in Hashimoto). One side lobectomy was
      performed in 103 patients with Hashimoto thyroiditis. Lymph node dissection was
      performed in 21 (1 in Graves and 20 in Hashimoto), in all central, in 10 lateral
      functional and in 6 mediastinal, in 15 patients with cancer and in 6 patients
      with benign disease. There was no operative mortality. In Graves' disease, there
      was postoperative bleeding in 4 (0.4%), wound infection in 2 (0.2%) recurrent
      pulsy in 18 (2%) and permanent hypoparathyroidism in 13 (1.4%). In Hashimoto
      thyroiditis, there was postoperative bleeding in 2 (0.4%), recurrent nerve pulsy
      in 11 (1.9%) and permanent hypoparathyroidism in 6 (1.1%). The most common
      surgical procedure in autoimmune thyroid disease is total thyroidectomy which is
      followed by low complication rate in specialised centers. Cancer is more frequent
      in Hashimoto than in Graves' disease.

PMID- 16405263
TI  - [Autoimmune thyroid disease and associated diseases].
AB  - Autoimmune thyroid disease (ATD) is a multifactorial, genetic disease. It is the
      sequelae of the impaired immunoregulation, tolerance and poor recognition of
      one's own proteins, oligopolysaccharides and polypeptides, due to development of
      somatic lymphocyte mutations. It is manifested by different clinical and
      morphological entities, inter-related by etiopathogenetic association, i.e., all
      of them are caused by disorder of immune system regulation. Chronic autoimmune
      thyroidism (Thyreoiditis lymphocytaria Hashimoto, HT), as well as immunogenic
      hyperthyroidism (Morbus Graves Basedow, MGB) are frequently associated with
      autoimmune diseases of other organs, such as: chronic insufficiency of salivary
      glands (Sy Sjogren), autoimmune hemolytic anemia, megalocytic pernicious anemia,
      thrombocytopenia, Rheumatoid arthritis, Diabetes mellitus (more often type 2, but
      also type 1), Morbus Addison, Coeliakia, and other autoimmune diseases such as
      systemic diseases of connecting tissue (Lupus erythematosus-SLE, Sclerodermia,
      Vasculitis superficialis). The incidence of autoimmune diseases has been at
      increase in all age groups of our population. The prevalence of organ-specific
      and organ-nonspecific antibodies increases with the age. Antigenicity of thyroid
      epithelial cell may be triggered by different chemical and biological agents
      (repeated viral infections), repeated stress, and in individuals with genetic
      propensity. Unrecognized ATD progressively leads to hypothyroidism with
      hyperlipidemia, blood vessel changes, osteoporosis, deformities, invalidity which
      substantially reduces the quality of life of patient and requires medical
      attention and expensive treatment on what account it is medically and socio
      economically significant. Multiple diagnostic procedures contribute to faster
      recognition of this condition. The goal of the primary health care physician
      (given that preclinical phase of ATD and other associated diseases have different
      duration) and other specialists is to recognize ATD and, by early diagnosis and
      multidisciplinary treatment, to take secondary preventive measures of
      manifestation of above-mentioned associated autoimmune diseases, and in that way,
      to avoid the development of comorbidity and complications. It is particularly
      supported by medical doctrine based on evidence of application of
      corticosteroids, cytostatics, thyro-suppressive and substitution therapy,
      antilipemics, bisphosphonates and other drugs, significant for autoimmune
      diseases.

PMID- 16405264
TI  - [Autoimmune thyroid disease and brain].
AB  - Changes of the affective and cognitive function are usually associated with
      thyroid gland dysfunction. In autoimmune thyroid disease, these changes can be
      caused by thyroid dysfunction (hypo- or hyperthyroidism) or associated with the
      presence of antithyroid antibodies. Even a small change in thyroid hormone
      concentration is associated with change of cognitive function. In euthyroid older
      males, variation of total and free thyroxin accounts for about 10% of Wechsler
      adult intelligence test variance. In euthyroid females, lower cognitive function,
      measured by Mini Mental test, also correlates with blood thyroxin. Short-term (4
      weeks) hypothyroidism induces clinically significant cognitivedysfunction, which
      is reversible by thyroid hormone substitution. Mild hypothyroidism (TSH less than
      10) also induces reversible cognitive dysfunction. In hypothyroidism, PET
      scanning shows global reduction of brain blood flow and glucose metabolism.
      Hashimoto's encephalopathy is characterized by corticosteroid reversible
      encephalopathy associated with the presence of antithyroid antibodies.
      Encephalopathy can be manifested as multiple stroke-like episodes (vasculitis
      like), or as diffuse, progressive type characterized by dementia and psychiatric
      symptoms. In euthyroid patients with Hashimoto's thyroiditis and no evidence of
      neurological disease, SPECT showed brain perfusion abnormalities. Post mortem and
      brain biopsy findings can be normal or show perivascular lymphocytic
      infiltration. Recently, presence of antineuronal antibodies has been found in
      patients with Hashimoto's thyroiditis. Specific high reactivity against human
      alpha-enolase was high in patients with Hashimoto's encephalopathy, but absent in
      patients with other neurological disorders and healthy subjects. Specific
      antineural antibodies were found in another group of Hashimoto's encephalopathy
      patients. Furthermore, Ferracci et al, found antithyroid antibodies in the CSF of
      patients with Hashimoto's encephalopathy.

PMID- 16405265
TI  - Improved visualisation to a range of procedures.

PMID- 16405266
TI  - Nasal obstruction and its impact on sleep-related breathing disorders.
AB  - Upper airway patency is essential during sleep in order to avoid sleep-related
      breathing disorders (SRBD). Nasal obstruction may have a negative impact on sleep
      quality and must be considered to be a co-factor in the pathophysiology of SRBD.
      In this paper we will discuss the relation between nasal physiology at night and
      sleep quality and the possible mechanisms between nasal obstruction and
      obstructive sleep apnea-hypopnea syndrome (OSAS). We will review the effect of
      the relief of nasal obstruction (with nasal dilators, medication and/or surgery)
      on SRBD. Also an algorithm on the management of OSAS patients when nasal surgery
      is indicated will be proposed.

PMID- 16405267
TI  - Ultrastructural ciliary findings in nasal obstructive diseases.
AB  - Specific ultrastructural findings have widely been described in case of
      obstructive nasal diseases due to congenital defects. Ciliary impairment has in
      particular been observed as the main pathological feature in these conditions. In
      this study, nasal mucosal samples from different pathologies have been collected
      via the "brushing" technique and analysed by transmission electron microscopy.
      TEM analysis was focused on specific features, such as the numerical array of
      peripheral and central doublets of the cilium axoneme, including eventual
      microtubular disarrangement; partial or total loss of inner and/or outer dynein
      arms; defects of radial spokes and nexin links; disorientation of the ciliary
      axis in closely adjacent cilia, calculating the angle between the line crossing
      the central microtubular core and the horizontal ciliary axis and compound cilia
      (CC). Statistical comparison was carried out between study and control groups. A
      significant incidence of organic ciliary defects was found not only in patients
      with inflammatory processes, but mostly in those supposed to have a long-lasting
      nasal respiratory disease due to mechanical stenosis in relation to septum
      deviation and turbinate hypertrophy. Prevalence and percentage of compound cilia
      were instead more related to inflammatory conditions. The "brushing" technique
      can be considered an easy and reliable method for the assessment of the condition
      of the nasal mucosa. According to the findings derived from this study,
      mechanical nasal obstruction seems to cause major alterations on the nasal
      ciliary arrangement, thus determining a functional impairment on the whole nasal
      function.

PMID- 16405268
TI  - Changes occurring in the nasal mucociliary transport in patients with one-sided
      septum deviation.
AB  - Septum deviation is the most commonly seen nasal pathology. Mucociliar activity
      can be affected by septum deviation that can be detected in many nasal
      pathologies. This study was aimed to compare the changes occurring in the
      mucociliary activities in both the nasal cavities of 20 patients with one-sided
      septal deviation and 20 healthy young individuals without septal deviation. The
      mucociliary activity of the right nasal cavity in healthy human beings and the
      mucociliary activity of the concave and convex sides of nasal cavities in
      patients with septal deviation were measured. Mucociliary clearance was measured
      by means of the rhinoscintigraphy technique. The mucociliary transport speed on
      the concave side was found to be significantly increased compared to the convex
      side and the control group. As a result, the mucociliary activity was within
      normal limits in patients with septum deviation who didn't have a nasal mucosal
      disease. Furthermore, the mucociliary activity was found to be increased on the
      concave side where the airflow was higher.

PMID- 16405269
TI  - Cytomorphologic and ultrastructural study of nasal mucosa by means of brushing: a
      comparison between asymptomatic and rhinitic subjects.
AB  - The authors compared the cytomorphologic and ultrastructural features of nasal
      epithelium collected by means of brushing from asymptomatic subjects with these
      of patients affected by nasal polyposis (NP), allergic (AR) and non-allergic
      rhinitis (NAR). A brushing of nasal epithelium was taken from each member of both
      groups, and analysed under light and electron microscopy. The observation showed
      normal ciliary patterns and preserved intercellular joints in the great majority
      of asymptomatic subjects, while in all subjects of the pathologic group the
      junctions appeared variously damaged or absents, with ciliary abnormalities. The
      damage to the intercellular joints, rather than the alterations of ciliary
      patterns, seemed to represent in this study the border between the absence of
      symptoms and the presence of chronic inflammation. Therefore, a reduced tightness
      of the intercellular joints could contribute to the impairment of the mucociliary
      clearance, priming the vicious circle that leads to the condition of chronic
      inflammation.

PMID- 16405270
TI  - Inhibitory effects of facemasks and eyeglasses on invasion of pollen particles in
      the nose and eye: a clinical study.
AB  - The incidence of Japanese cedar pollinosis is estimated to be about 13% of the
      Japanese population. In Japan it is generic to wear a facemask and eyeglasses to
      prevent pollen inhalation. We examined the usefulness of a facemask and
      eyeglasses in cooperation with volunteers. The number of pollen particles in the
      nasal cavity and on the conjunctiva was unchanged by wearing a facemask and
      eyeglasses. However, the pollen invasion rate was lower in subjects with a
      facemask and eyeglasses than in subjects without a facemask and eyeglasses. The
      decrease in pollen invasion rate in the nasal cavity due to wearing a facemask
      was statistically significant. This suggested that wearing a facemask has a
      protective effect on pollen invasion to the nose. The pollen invasion rate in the
      nasal cavity and on the conjunctiva was increased with increases in the wind
      speed. It may be difficult to avoid pollen even when wearing a facemask and
      eyeglasses when the wind speed is high. Further study is required to clarify the
      relationship between the amount of allergens and clinical symptoms.

PMID- 16405272
TI  - Closure of cerebrospinal fluid leaks prevents ascending bacterial meningitis.
AB  - INTRODUCTION: Endoscopic surgery of the anterior skull base has become the
      standard procedure for the repair of cerebrospinal fluid (CSF) leaks of various
      origins. Closure of the leaks is believed to prevent ascending meningitis,
      although no report has specifically shown this. MATERIAL AND METHODS:
      Retrospective chart study of 39 patients who underwent endoscopic skull base
      surgery from 1/1993 to 11/2002. SETTING: Tertiary University Hospitals. OUTCOME
      MEASUREMENT: Incidence of ascending meningitis after endoscopic skull base repair
      in patients with anterior skull base defects associated or not with meningitis
      and CSF leak. RESULTS: Forty-one endoscopic repairs of anterior skull base
      defects of various origins were performed in 39 patients. Fifteen (36.5%) had
      suffered bacterial meningitis before surgery. Mean follow-up was 65 months (range
      22-120). The defect was repaired using an "underlay" technique with lyophilized
      dura (n=11) or fascia lata (n=30), and covered with free mucosal grafts from
      either the middle or the inferior turbinates. Closure was achieved in 40/41 cases
      at first attempt. No recurrence of ascending bacterial meningitis was observed
      during follow-up in any of the fifteen patients who had previously presented with
      a CSF leak or skull base defect with meningitis. Also, no new bacterial
      meningitis occurred in all other patients. One case of meningoencephalocele of
      the lateral sphenoid wall developed a recurrent CSF fistula associated with
      bacterial meningitis two years after endoscopic repair, requiring endoscopic
      revision surgery. No patient received vaccination in this series. DISCUSSION:
      Closure of active CSF leaks and reconstruction of skull base defects without CSF
      leak in patients with prior ascending bacterial meningitis seem to provide
      excellent long-term results with neither recurrence of ascending meningitis nor
      incidence of meningitis in the other patients, unless a CSF leak re-appears.
      Conservative treatment of CSF leaks may lead to bacterial meningitis, therefore
      surgical closure of leaks or defects at the skull base should be considered
      treatment of choice to prevent ascending meningitis.

PMID- 16405271
TI  - Endoscopic and microscopic paraseptal transsphenoidal approach to the sella
      turcica.
AB  - OBJECTIVES: To establish the feasibility of the paraseptal approach to the sella
      and to demonstrate the superiority of the endoscopic over the microscopic vision
      during pituitary surgery. STUDY DESIGN: Prospective monocentric study. METHODS:
      Nine consecutive patients with a pituitary tumour were operated since November
      2002. The surgical procedure consisted of a paraseptal approach of the sella with
      use of a rigid endoscope. Pre- and postoperative (3 months after surgery)
      symptoms, Magnetic Resonance Imaging (MRI) findings, endocrine and ophthalmic
      assessment, and intraoperative findings were recorded. RESULTS: One patient
      presented a CSF leak with a successful peroperative repair. Regarding symptom
      resolution, headache disappeared during the early postoperative period in case of
      pituitary apoplexy. All cases of preoperative hemianopsia and diplopia but one
      improved significantly. Two patients recovered preoperative deficient hormonal
      functions and six patients did not require substitution therapy any more. No
      nasal packing was needed except in one case. Considering the healing course, the
      mucosa repair inside the sphenoid sinus was quicker with Surgicel removal at week
      4. Postoperative MRI demonstrated a residual parasellar nodule in 3 out of 6
      cases of macroadenoma. Only one required radiation therapy. These results are
      commented through comparison with the transseptal approach and with surgery
      exclusively using the microscope. CONCLUSIONS: The paraseptal transsphenoidal
      approach to the sella turcica using the telescope is at least as effective as the
      conventional transseptal approach using the operating microscope only. It
      provides a wide access to the pituitary fossa and an optimal vision of the
      critical areas. The absence of postoperative nasal packing improves significantly
      the comfort of the patient during the first postoperative hours.

PMID- 16405273
TI  - Endoscopic resection of juvenile angiofibromas--long term results.
AB  - OBJECTIVE: To evaluate the long term outcome after endoscopic endonasal resection
      of juvenile nasopharyngeal angiofibromas (JNA). METHODS: Retrospective study of a
      series of 21 consecutive patients undergoing endoscopic resection of JNA (type I 
      IIIa according to Fisch) at two Hospital Centers between 1993 and 2002. Mean
      follow-up was 51.7 months (range 5-120). Extension to the medial aspect of
      infratemporal fossa and retromaxillary space was no contraindication against an
      endonasal endoscopic approach. In three cases of type IIIa tumours a computer
      assisted intraoperative guiding system was applied (ENTrak, GE Medical, Lawrence,
      USA). RESULTS: Fifteen patients (71.4%) were free of disease after one endoscopic
      resection. Three patients (14.3%) had an unmistakable recurrence with the need
      for further treatment at 6, 14, and 23 months, respectively. Two of the three
      recurrent tumours have been successfully resected endoscopically, one case was
      treated with gamma knife. In three patients (14.3%) postoperative MRI showed
      localized enhanced signal, presumably minimal persistent tumour tissue. Without
      further treatment all of these patients remained free of symptoms and MRI follow
      up showed no tumour growth over three, five and ten years, respectively. No
      postoperative long term sequela was observed. CONCLUSIONS: Resection of
      nasopharyngeal angiofibromas type I-IIIa can be safely achieved endoscopically.
      The advantage of this minimally invasive technique is avoidance of external scars
      and low morbidity. The intraoperative computer assisted guiding system ENTrak was
      highly accurate and provided substantial help in selected cases.

PMID- 16405274
TI  - Decongestant effects of nasal xylometazoline and mometasone furoate in persistent
      allergic rhinitis.
AB  - Thirty-six persistent allergic rhinitis (PAR) sufferers were studied, to both
      compare and correlate 15 minute response to nasal xylometazoline (XYLO) with 28
      day response to nasal mometasone furoate (MF). 0.1% XYLO (1 spray each nostril)
      response was measured on two occasions, then a randomised double blind cross-over
      comparison of MF (200 mcg daily) to placebo conducted. Outcomes were peak nasal
      inspiratoly flow (PNIF), nasal forced inspiratory volume in one second (nFIV1)
      and nasal blockage score (NBS) improvements. Thirty-one participants completed
      per protocol. Within subject standard deviation for percentage improvement to
      XYLO was 26.0 for PNIF and 25.2 for nFIV1. Median % improvement (95%CI) in PNIF
      for XYLO vs. MF was 20.0 (11.4 to 31.0) vs. 9.6 (3.2 to 15.8) and in nFIV1 was
      17.8 (10.0 to 28.1) vs. 3.3 (-4.3 to 19.1). XYLO effects were greater than MF
      (p<0.05) for PNIF, nFIV1 and NBS. There was no significant correlation of MF to
      XYLO improvements in PNIF, nFIV1 or NBS. In conclusion, acute reversibility to
      XYLO showed poor repeatability and XYLO reversibility is not predictive of
      decongestant response to nasal corticosteroid. XYLO was a stronger decongestant
      than MF but rhinitis medicamentosa still precludes any preference for long term
      XYLO therapy at this time.

PMID- 16405275
TI  - Nasal resistance for determinant factor of nasal surgery in CPAP failure patients
      with obstructive sleep apnea syndrome.
AB  - OBJECTIVES: Given that criteria for nasal surgery in individuals with obstructive
      sleep apnea syndrome (OSAS) have not been proposed, we investigated the
      effectiveness of nasal surgery for CPAP failure in patients with both severe OSAS
      and nasal obstruction. PATIENTS AND METHODS: Conventional nasal surgery was
      performed in 12 patients who were refractory to treatment by CPAP. The subject
      group consisted of 12 males (mean age, 54.2 +/- 9.2 years; range 39-66 years).
      The effect of nasal surgery was evaluated with data from preoperative and
      postoperative polysomunography. The nasal resistance value was first deduced to
      determine which OSAS patients with CPAP failure should undergo nasal surgery,
      compared to control values. RESULTS: Nasal surgery resulted in a significant
      decrease in nasal resistance, as measured by rhinomanometry, from 0.57 +/- 0.31
      Pa/cm3 /sec to 0.16 +/- 0.03 Pa/cm3/sec and rendered all patients tolerant to
      CPAP. In addition, the lowest nocturnal oxygen saturation significantly increased
      from 68.3 +/- 12.1% to 75.3 +/- 7.1% after surgery. Subjectively, Epworth
      sleepiness scale (ESS) significantly decreased from 11.7 +/- 4.1 to 3.3 +/- 1.3
      after surgery, but the number of apnea and hypopnea episodes per hour did not
      change significantly. In five patients, for whom it was possible to perform a
      CPAP titration before nasal surgery, the value decreased significantly from 16.8
      +/- 1.1 to 12.0 +/- 1.9 cmH2O. The bilateral nasal resistance of the 410SAS
      patients with CPAP therapy (control group) was 0.24 +/- 0.11 Pa/cm3/sec. The cut
      off value for differentiation between CPAP failure patients and control group was
      determined as 0.38 Pa/cm3 /sec. CONCLUSION: Increased nasal resistance is a
      determinant of CPAP failure, and the surgical correction of severe nasal
      obstruction should thus be considered to facilitate treatment of OSAS patients
      with CPAP.

PMID- 16405276
TI  - Posterior epistaxis: systematic review on the effectiveness of surgical
      therapies.
AB  - OBJECTIVE: The optimal surgical treatment for patients with posterior epistaxis
      and failed conservative therapy is unknown. Therefore we planned a systematic
      review studying all available publications assessing the effect on bleeding
      recurrence and postoperative complications of ligation of the internal maxillary
      artery or the sphenopalatine artery. METHODS: We searched the electronic
      databases Medline, Medline In Process, and Cochrane Library. Data extraction was
      performed following standard methods. RESULTS: Twenty-eight studies could be
      included in the systematic review. All studies were retrospective and no single
      study comparing different methods could be identified. Fifteen studies reported
      on the effect of the ligation of the internal maxillary artery (LIMA) and 13 on
      the effect of the ligation of the sphenopalatine artery (LSA). The severity of
      postoperative complications and duration of hospital stay seem to be lower in the
      LSA group. A conclusive statement about the frequency of rebleeding in the two
      groups is not possible. CONCLUSION: According to the available data on
      postoperative complications and duration of hospital stay ligation of the
      sphenopalatine artery compared favourably to the ligation of the internal
      maxillary artery. The most effective treatment for patients with posterior
      epistaxis including costs should be evaluated in a controlled clinical trial.

PMID- 16405277
TI  - Persistent epistaxis: what is the best practice?
AB  - Epistaxis is the commonest otolaryngological emergency, which is often managed by
      a nasal pack. A significant number of cases fail to respond to nasal packing and
      various surgical measures are available to control the nosebleed in these cases.
      However evidence is sparse regarding the best available surgical option for the
      management of persistent epistaxis. We designed a retrospective cohort study
      comparing endoscopic ligation of sphenopalatine artery (ELSA) and all other
      surgical options (non-ELSA) in the management of persistent epistaxis. All
      consecutive cases of persistent epistaxis between 1997-2004 (Feb) requiring
      operative intervention were included in the study and divided in two groups
      according to the surgical intervention. Postoperative epistaxis was excluded. Non
      ELSA group consisted of various procedures including nasal cautery and packing,
      submucous resection, anterior ethmoid artery ligation, external carotid artery
      ligation, internal maxillary artery ligation. Both groups were matched for age,
      sex, risk factors, other medical conditions and medications. The main outcome
      measures evaluated were immediate success in arresting the bleeding and the mean
      hospital stay. Recurrence and patient acceptability of the procedure were the
      secondary variables investigated. We found that ELSA proved to be the best
      practice to manage persistent epistaxis on all measures of immediate success
      rate, shorter hospital stay, recurrence rate, and patient satisfaction.

PMID- 16405278
TI  - Isolated fibrous dysplasia of the sphenoid sinus.
AB  - Fibrous dysplasia is an uncommon benign bone disorder of unknown etiology in
      which normal medullary bone is replaced by fibrotic and osseous tissue. Solitary
      involvement of the sphenoid sinus is unusual. Here, we present the case of a 28
      year-old man complaining of occipital and vertical headache. Imaging modalities
      demonstrated an expansile lesion filling the entire sphenoid sinus. Biopsy
      specimen was obtained by endoscopic sphenoidotomy. Diagnosis of fibrous dysplasia
      was made by imaging results and pathologic examination.

PMID- 16405279
TI  - Silent sinus syndrome, a case presentation.
AB  - "Silent Sinus Syndrome" is a quite rare condition of otherwise asymptomatic
      maxillary sinusitis that presents with enophthalmos. Despite the fact that the
      "Silent Sinus Syndrome" presents with enophthalmos, these patients are finally
      treated by the otorhinolaryngologist, who should be familiar with this condition,
      in order to facilitate prompt diagnosis and treatment. We present the case of a
      33 year old man with enophthalmos and no other associated symptom that was caused
      by chronic rhinosinusitis. Functional endoscopic sinus surgery was the treatment
      of choice. No reconstruction of the orbital floor was performed. One year follow
      up, following surgical treatment revealed an excellent result.

PMID- 16405280
TI  - Current position of the management of community-acquired acute maxillary
      sinusitis or rhinosinusitis in France and literature review.

PMID- 16405281
TI  - [Getting older begins with birth. But at first it goes up hill! Does that mean
      that it goes downhill later?].

PMID- 16405282
TI  - [Nutrition and osteoporosis. When is a supplementation with calcium and vitamin
      D3 useful?].

PMID- 16405283
TI  - [On the wisdom and stupidity of getting older--a progress report].

PMID- 16405284
TI  - [Memory and planning].
AB  - The years before and after retirement are characterized by substantial changes in
      the lifes' of aging individuals. However, the same changes may be appraised as
      stressful, neutral, or positive, depending on the available skills, experiences,
      and future expectations. In other words, the subjective experience of cognitive
      aging strongly determines health-related behaviors and, thus, the effectiveness
      of treatments. An area of increasing concern in this age group is the development
      of one's cognitive abilities. The demand for adequate trainings to preventively
      maintain cognitive skills plays an important role. Persons may also start
      worrying if observed changes in their memory performance are still in the range
      of normal functioning or if they may represent early indications of dementia.
      This paper (a) briefly describes normal cognitive development between 50 and 75
      years, (b) provides examples for the plasticity of cognitive abilities, (c)
      highlights the importance of subjective memory complaints for the detection of
      mental health and memory problems, and (d) suggests a procedure to help detecting
      memory problems early on.

PMID- 16405285
TI  - [Men and women--aspects of sexological counseling in the aging].
AB  - In our times, sexuality has become an essential part of life for aging people.
      For the aging, psychosocial and biological changes, as well as increasing
      morbidity present challenges to a satisfying sexual life. Hence, the demand grows
      for health-care providers with basic sexological knowledge and counseling
      abilities. This article discusses relationships between frequent sexual
      difficulties and aging related organic processes. A therapeutic concept, the
      "Sexocorporal Approach", is introduced. This approach is based on a model of
      ongoing sexual development throughout the lifetime enabling adaptation to new
      life phases and limiting circumstances through sexual learning processes. Aside
      from pharmacological treatment, the encouragement of sexual learning presents an
      effective therapeutic approach for practitioners that can be easily learned and
      applied.

PMID- 16405286
TI  - [Caring for women during perimenopause in the practice].
AB  - This article wants to make sure, that women with menopausal complaints receive
      evidence-based advice and psychosomatically oriented treatment. The published
      evidence for efficacy, safety, and risks of all investigated treatments of
      menopausal symptoms is reviewed. Estrogen/progestin therapy is the most effective
      treatment for reducing the frequency of hot flashes (75%). Placebo reduces the
      frequency of hot flashes by about 58% which confirms the very high rate of
      spontaneous remission of climacteric symptoms. It appears worthwhile to avoid the
      risks of estrogen/progestin therapy whenever possible und to support women in
      their efforts to tolerate a slight degree of discomfort from hot flushes.
      Alternative and complementary medical treatments must prove they are more
      effective than placebo especially, in particular as long as the risks are
      insufficiently evaluated.

PMID- 16405287
TI  - [Andropause].
AB  - The terms andropause, partial androgen deficiency of the aging male (PADAM) or
      late-onset hypogonadism (LOH) describe a clinical entity which has been defined
      as a syndrome associated with advanced age. This syndrome is characterised by a
      deficiency in serum testosterone levels that may result in significant
      alterations in the quality of life and adversely affect the function of multiple
      organ systems. Whereas in classic primary and secondary hypogonadism, the
      clinical picture of testosterone deficiency is clearly defined, the clinical
      diagnosis of PADAM might escape detection for various reasons: not all signs and
      symptoms necessarily present together; they often progress slowly and are subtle
      in nature; the non-specific signs and symptoms might not be discernible from the
      unavoidable process of aging itself. However, PADAM features many potentially
      serious consequences that can be avoided or treated, and is, therefore,
      clinically relevant. Testosterone substitution may be an effective way to manage
      this condition. Once patients begin treatment with testosterone substitution,
      follow-up and monitoring are essential.

PMID- 16405288
TI  - [Cardiovascular system and aging].
AB  - Aging is one of the most important cardiovascular risk factors. Age-related
      morphologic changes in large resistance vessels include an intima-media
      thickening and increased deposition of matrix substance, ultimately leading to a
      reduced compliance and an increased stiffness of the vessels. Aging of the heart
      is mainly characterized by an increase of the left ventricular mass in relation
      to the chamber volume and a decrease of diastolic function. There is some
      controversy in regard to the question if these changes in the vessel wall are the
      consequence of aging or if a decrease in physical activity is a major contributor
      of this process. With age the cardiovascular profile is changing. Whereas smoking
      is less prominent, arterial hypertension and diabetes mellitus are more often
      encountered. Primary and secondary prevention through cardiovascular risk factor
      management is also very important in the aging population due to the increased
      risk of acute vascular complications with age. Preventive measures have to
      include life style factor interventions as well as optimized drug therapy. There
      is no scientific evidence that vascular aging can be prevented by administration
      of supplements such as antioxidant vitamins. Aspirin is effective for
      cardiovascular prevention up to a higher age. Betablockers and ACE-inhibitors are
      generally underused in older patients after myocardial infarctions. Statins are
      effective in reducing cardiovascular complications up to an age of 80 years.
      Myocardial infarction in elderly patients is often characterized by atypical
      symptoms and may be even silent. Interventional therapy in elderly patients is as
      successful as in younger patients but has an increased complication rate.
      Ambulatory cardiac rehabilitation in elderly patients leads to significant
      improvements of physical capacity, well-being and quality of life and may help to
      prevent social isolation.

PMID- 16405289
TI  - [Aging of skin and hair].
AB  - Anti-aging medicine is dedicated to the advancement of technology to detect,
      prevent, and treat aging related disease and to promote research into methods to
      retard and optimize the aging process. Dermatology offers good basics for
      rational preventive and therapeutic anti-aging strategies. The role of the skin
      in anti-aging medicine is not merely that aging is most obvious on the skin, but
      that the skin is a highly accessible and unique organ that offers unequaled
      opportunities to the gerontologist for the study of age-related effects. The
      study of skin aging focuses on two main streams of interest: On one hand, the
      esthetic problem and its management; on the other, the biological problem of
      aging in terms of microscopic, biochemical, and molecular changes. Probably the
      same molecular mechanisms underlying the aging of skin and its appendages,
      including the pigmentary system, underlie age-dependent degenerative changes of
      the inner organs and entire organism. The skin and hair are subject to intrinsic
      or physiologic aging, and extrinsic or premature aging due to external factors.
      Intrinsic factors are related to individual genetic and epigenetic mechanisms
      with interindividual variation. Extrinsic factors include ultraviolet radiation
      and cigarette smoking. Primary prevention encompasses measures that are taken
      before the aging process has started, secondary prevention when the first signs
      of aging have come into sight. Eventually, tertiary measures are aimed at
      correcting established signs of aging. Prevention starts with photoprotection and
      avoidance of cigarette smoking. In dermatologic practice sun protecting agents,
      dermocosmetic substances, hair growth promoting agents, and anti-aging compounds
      play an ever increasing role. Finally, tertiary anti-aging measures include
      minimally invasive cosmetic procedures such as chemical peels, microdermabrasion,
      soft tissue fillers, non-ablative laser rejuvenation, radiofrequency techniques
      and botulinum toxin, as well as laser skin resurfacing and corrective surgical
      procedures, including autologous hair transplantation.

PMID- 16405290
TI  - [Eating and drinking during aging].
AB  - The retirement is a good moment in life to mirror one's health behaviour in
      regard to eating habits and physical activity. Based on the literature we
      recommend the Mediterranean "diet" in all ages. This diet is characterized by the
      intake of fresh fruit, vegetables, cereals, olive oil, fish, little meat,
      legumes, spices and herbs such as basil and garlic. A glass wine a day is
      legitimate. In increasing age total energy needs are decreasing. Therefore the
      energy intake has to be adjusted. Caloric restriction per se is a powerful means
      to reduce cardiovascular morbidity and mortality. However, not only the eating
      habits but also the entire lifestyle are important factors to influence
      cardiovascular mortality. Thus, the "low risk factors", i.e. Mediterranean diet,
      moderate alcohol consumption, physical activity and non-smoking must be
      controlled to improve health. In the HALE project the control of these factors
      reduced over-all mortality by 65 percent!

PMID- 16405292
TI  - Fish-isolated strains of Hartmannella vermiformis page, 1967: morphology,
      phylogeny and molecular diagnosis of the species in tissue lesions.
AB  - Based on morphological and molecular characterisation, four amoeba strains
      isolated from organs of freshwater fish were identified as Hartmannella
      vermiformis Page, 1967. Small subunit rRNA gene sequences of these strains expand
      the set of corresponding complete and almost complete sequences of this species
      to twelve. A new species-specific oligonucleotide probe inferred from recently
      available SSU rRNA gene sequences was designed and successfully tested in tissue
      lesions produced by one strain of H. vermiformis in experimentally infected fish.

PMID- 16405291
TI  - Lyme borreliosis: insights into tick-/host-borrelia relations.
AB  - Lyme borreliosis (LB) is a serious infectious disease of humans and some domestic
      animals in temperate regions of the Northern Hemisphere. It is caused by certain
      spirochetes in the Borrelia burgdorferi sensu lato (s.l.) species complex. The
      complex consists of 11 species (genospecies). Borrelia burgdorferi sensu stricto
      (s.s.), Borrelia garinii and Borrelia afzelii are the major agents of human
      disease. Borrelia burgdorferi s.l. species are transmitted mainly by ticks
      belonging to the Ixodes ricinus species complex plus a few additional species not
      currently assigned to the complex. B. burgdorferi infections may produce an acute
      or chronic disease with a wide array of clinical symptoms such as erythema
      migrans (EM), carditis, arthritis, neuroborreliosis, and acrodermatitis chronica
      atrophicans (ACA). Differences in LB spirochetes 'genospecies' and
      strains/isolates determine the occurrence and severity of this multi-system
      disease. Accurate and reliable identification of the LB spirochetes in ticks as
      well as knowledge of their prevalence are essential for prevention against the
      disease and development of an effective vaccine. An overview of the knowledge of
      molecular factors with emphasis on potential protein-carbohydrate interactions in
      the tick-borrelia system is the main focus of this review.

PMID- 16405293
TI  - Trilosporoides platessae gen. et sp. n. (Myxozoa: Multivalvulida) in the plaice
      Pleuronectes platessa (Teleostei: Pleuronectidae) from Denmark.
AB  - A new myxosporean species, Trilosporoides platessae gen. et sp. n.
      (Multivalvulida), is described from the gallbladder of the plaice Pleuronectes
      platessa L. (Pleuronectidae) from Denmark. The myxospore of T. platessae is
      conical in side view, with a 24 microm long, pointed posterior projection. In
      apical view, the myxospore (diameter 9.4 microm) is round, trilobed and with
      three spherical polar capsules arranged peripherally, equidistant and opening
      peripherally through protruding tips. The polar capsules are of different sizes,
      one often larger than the others (diameter 3.3 microm vs. 2.5 microm). Apart from
      the long posterior projection, the myxospore of T. platessae differs from those
      of the three known species of Trilospora Noble, 1959 and from all genera within
      the order Multivalvulida Shulman, 1959 in the arrangement of the polar capsules.
      Trilosporoides platessae may temporarily be placed in the vicinity of the
      Trilosporidae.

PMID- 16405294
TI  - A new species of Mymarothecium and new host and geographical records for M.
      viatorum (Monogenea: Dactylogyridae), parasites of freshwater fishes in Brazil.
AB  - Mymarothecium boegeri sp. n. (Monogenea: Dactylogyridae) is described from the
      gills of Colossoma macropomum Cuvier (Characidae), collected from the aquaria of
      the "Centro de Pesquisas em Aquicultura, Departamento Nacional de Obras Contra as
      Secas (DNOCS)", Pentecoste City, State of Ceara, Brazil. Mymarothecium viatorum
      Boeger, Piasecki et Sobecka, 2002 is reported from the type host, Piaractus
      brachypomus (Cuvier) (Characidae) and from a new host, P. mesopotamicus
      (Holmberg) (Characidae), confirming the occurrence of M. viatorum in the
      Neotropical Region. The new species differs from the congeneric species in the
      structure of male copulatory complex; it is more closely related to M. viatorum
      by the presence of a posteromedial projection on ventral bar.

PMID- 16405295
TI  - Morphological characterisation of Paranoplocephala bairdi (Schad, 1954) (Cestoda:
      Anoplocephalidae) in heather voles Phenacomys spp. and tree voles Arborimus spp.,
      and related species in voles and lemmings (Muridae: Arvicolinae).
AB  - The taxonomical status of Paranoplocephala bairdi (Schad, 1954)-like cestodes
      (Anoplocephalidae) in heather voles Phenacomys spp. and tree voles Arborimus spp.
      (Muridae: Arvicolinae) and their discrimination from five related species of
      Paranoplocephala is assessed using uni- and multivariate morphometrics. The
      analyses support the independent status and conspecificity of specimens from
      Phenacomys spp. and Arborimus spp., and P. bairdi is therefore suggested to be a
      host-specialist species of heather and tree voles with a wide geographical
      distribution in North America. A redescription is presented for P. bairdi.

PMID- 16405296
TI  - Fine structure of the female reproductive ducts of Cyathocephalus truncatus
      (Cestoda: Spathebothriidea), from salmonid fish.
AB  - The fine structure of the ovary, ovicapt, oviduct, fertilisation canal, vitelline
      ducts, vitelline reservoir, ovovitelline duct, ootype and Mehlis' gland, and
      proximal, middle and distal parts of the uterus of the spathebothriidean cestode,
      Cyathocephalus truncatus (Pallas, 1781), from salmoniform fish, has been studied
      for the first time by transmission electron microscopy (TEM). Emphasis was given
      to characteristics which might shed light on the unclarified phylogenetic
      position of spathebothriideans, belonging among the most basal tapeworms
      (Eucestoda). New for cestodes is the finding of a multinucleate cell that plugs
      the ovicapt lumen. The morphology of the proximal part of the oviduct resembles
      that of the pseudophyllidean tapeworm Diphyllobothrium latum. After fertilisation
      in the fertilisation canal, vitellocytes of C. truncatus become associated with
      fertilized oocytes in the ovovitelline duct. Only one type of Mehlis' gland
      secretory cell is present. The eggs with electron-dense eggshells containing
      large pores first appear in the proximal part of the uterus. The middle portion
      of the uterus has well-developed uterine glands. The distal portion of the uterus
      has apical microtriches. Ultrastructural data on the female genital system of C.
      truncatus are compared and discussed with those for other cestodes. However, on
      the basis of available ultrastructural data it is not possible to conclude
      whether the Spathebothriidea are phylogenetically closer to the Caryophyllidea or
      to the Pseudophyllidea.

PMID- 16405297
TI  - Rhabdias kongmongthaensis sp. n. (Nematoda: Rhabdiasidae) from Polypedates
      leucomystax (Amphibia: Anura: Rhacophoridae) in Thailand.
AB  - Rhabdias kongmongthaensis sp. n. is described based on specimens found in the
      lungs of the tree frog Polypedates leucomystax (Gravenhorst) (Amphibia:
      Rhacophoridae) from Kanchanaburi Province, western Thailand. The new species is
      similar to two North-American species, Rhabdias ranae and R. americanus, by
      presence of two lateral pseudolabia, each with two inner submedian protuberances.
      R. kongmongthaensis differs from both species by relative length and shape of the
      tail, and by its distribution and host specificity. Presence of lateral
      pseudolabia distinguishes the new species from the geographically closest
      Rhabdias species as well as from those parasitizing other rhacophorid frogs.

PMID- 16405298
TI  - Cucullanus oceaniensis sp. n. (Nematoda: Cucullanidae) from Pacific eels
      (Anguilla spp.).
AB  - A new species of parasitic nematode, Cucullanus oceaniensis sp. n., is described
      from the intestine of the giant mottled eel Anguilla marmorata (type host) from
      Futuna Island (Wallis and Futuna Islands, Polynesia) and from A. marmorata and
      Anguilla sp. (cf. obscura) from Fiji Islands (Melanesia, South Pacific). The main
      distinguishing characteristics are the length of spicules (668-1,020 microm),
      situation of deirids (slightly anterior to the oesophago-intestinal junction) and
      the excretory pore (some distance posterior to the end of oesophagus), and the
      arrangement of caudal papillae in the male. It is the third known species of
      Cucullanus from Oceania and the first one reported from freshwater eels in the
      region of South Pacific. Cucullanus faliexae Morand et Rigby, 1998 is considered
      a junior synonym of Cucullanus australiensis Baylis, 1927.

PMID- 16405299
TI  - A new genus of parasitic copepod (Siphonostomatoida: Caligidae) from the
      razorback scabbardfish, Assurger anzac (Trichiuridae) off New Caledonia.
AB  - A new genus and species, Avitocaligus assurgericola gen. et sp. n., of the family
      Caligidae is established based on an ovigerous female collected from a razorback
      scabbardfish, Assurger anzac (Alexander), caught off New Caledonia. This is the
      first record of any parasitic copepod from this fish. The new genus is placed in
      the Caligidae since it possesses the caligid cephalothorax incorporating the
      first to third pedigerous somites. It also exhibits biramous first and fourth
      swimming legs but lacks dorsal plates on the fourth pedigerous somite. This
      combination of characters serves to differentiate the new genus from existing
      genera. In addition, it possesses loosely coiled, uniseriate egg sacs, concealed
      between the middle lamellar plates on the genital complex and the ventral plates
      on the abdomen. Preliminary phylogenetic analysis with a restricted matrix
      suggests that the new genus represents the earliest offshoot from the main
      caligid lineage since it does not exhibit the dominant exopod on the fourth
      swimming leg found in all other members of the Caligidae, including the genus
      Euryphorus. It strongly supports the newly recognized monophyletic status of the
      Caligidae, incorporating the genera formerly placed in the Euryphoridae.

PMID- 16405300
TI  - Prevalence of Hemolivia mauritanica (Apicomplexa: Adeleina: Haemogregarinidae) in
      natural populations of tortoises of the genus Testudo in the East Mediterranean
      region.
AB  - Hemolivia mauritanica (Sergent et Sergent, 1904) infections were found in 14% (n=
      14) of Testudo graeca Linnaeus, 1758 tortoises in Bulgaria and in 92% (n = 26) of
      those in Turkey. Hemolivia mauritanica-like gametocytes were found in 81% (n =
      47) of wild Testudo marginata Schoepff, 1792 tortoises in Greece. Parasitaemia
      intensity (the percentage of infected red blood cells found in approximately 104
      cells) was 0.03-22.4% in T. graeca and 0.06-12.27% in T. marginata. On the other
      hand, all blood samples from 40 Bulgarian, 38 Greek, and 18 Croatian specimens of
      Testudo hermanni Gmelin, 1789 were negative.

PMID- 16405306
TI  - Quantum dynamics study on the product branching for the C(3P) + C2H2 reaction:
      cyclic-C3H versus linear-C3H.
AB  - Reduced-dimensionality quantum reactive scattering calculations for the C(3P) +
      C2H2 reaction have been carried out in order to understand the product branching
      dynamics of cyclic-C3H + H and linear-C3H + H. Our model treats only two degrees
      of freedom but can explicitly describe both of the C3H isomer product channels.
      The lowest triplet potential energy surface has been obtained by the hybrid
      density-functional method at the B3LYP/6-31G(d,p) level of theory. The calculated
      reaction probabilities were found to be dominated by resonance consistent with
      the complex-formation potential, and the results show that cyclic-C3H is
      preferentially formed via the cyclic-C3H2 intermediate produced by insertion of
      C(3P) into the CC bond. We have found that the isomerization from the cyclic-C3H2
      to linear-C3H2 intermediate is suppressed by a barrier separating potential wells
      corresponding to these two intermediates. It has also been found that the energy
      dependence of the calculated total reaction cross section is in good agreement
      with the result of crossed molecular beam experiments.

PMID- 16405301
TI  - Glycoprotein A34, a novel target for antibody-based cancer immunotherapy.
AB  - To identify novel, tissue-restricted cell surface proteins in cancer which can
      serve as targets for antibody-based diagnostics and therapeutics, a translated
      version of the expressed sequence tag database (tblastn) was mined for
      transcripts with similarity to the glycoprotein A33 (GPA33) colon cancer antigen.
      A novel human transcript, termed A34, was identified which encoded a putative
      cell surface protein, GPA34, which is approximately 30% identical to GPA33 and
      other members of the junctional adhesion molecule (JAM) family. Conventional end
      point and quantitative real-time RT-PCR showed that A34 mRNA expression is highly
      tissue-restricted, as it is expressed predominantly in stomach and testis. A34
      mRNA was also detected in 6/19 (31%) gastric cancers, 8/16 (50%) esophageal
      carcinomas, and 4/17 (23%) ovarian cancers, but not in lung, breast or colon
      carcinomas. A murine monoclonal antibody (mAb A34) was generated to the
      extracellular domain of the A34 protein and used to biochemically and
      immunohistochemically characterize the A34 antigenic system. The mAb A34
      specifically recognized glycoproteins ranging in apparent size from 55-70 kDa,
      present in normal gastric mucosa and in COS-7 cells transfected with A34 cDNA. Of
      31 different normal tissues examined by immunohistochemistry, GPA34 protein
      expression was detected primarily in normal stomach mucosa and testicular germ
      cells, and in the tumor cells of 5/17 (29%) gastric cancers, 7/11 (63%)
      esophageal cancers, and 2/21 (9%) ovarian cancers, in agreement with gene
      expression results. The A34 antigen and monoclonal antibody may be of
      considerable value for immunotherapy of different types of cancer.

PMID- 16405307
TI  - Is the mechanism of the [2+2] cycloaddition of cyclopentyne to ethylene concerted
      or biradical? A completely renormalized coupled cluster study.
AB  - The mechanism of the [2+2] cycloaddition reaction of cyclopentyne to ethylene has
      been studied using the completely renormalized coupled cluster method with
      singles, doubles, and noniterative triples (CR-CCSD(T)). In agreement with the
      experimentally observed stereochemistry, the CR-CCSD(T) method favors the
      concerted pathway involving a [2+1] transition state, whereas the popular CCSD(T)
      method, which is often regarded as the "gold standard" of electronic structure
      theory, and low-order multireference methods support the less probable biradical
      mechanism. In addition, the CCSD(T) approach produces an erroneous description of
      some transition states and intermediates, particularly those which have a
      significant biradical character. The CR-CCSD(T) calculations indicate that the
      reaction is a highly exothermic (deltaG(r)298 = -68 kcal/mol), predominantly
      concerted process with a relatively low activation barrier on the order of 13-16
      kcal/mol which permits its thermal occurrence.

PMID- 16405308
TI  - Including anharmonicity in the calculation of rate constants. 1. The HCN/HNC
      isomerization reaction.
AB  - A method for calculating anharmonic vibrational energy levels in asymmetric top
      and linear systems that is based on second-order perturbation theory in
      curvilinear coordinates is extended to the bound generalized normal modes at
      nonstationary points along a reaction path. Explicit formulas for the
      anharmonicity coefficients, x(ij), and the constant term, E0, are presented, and
      the necessary modifications for resonance cases are considered. The method is
      combined with variational transition state theory with semiclassical
      multidimensional tunneling approximations to calculate thermal rate constants for
      the HCN/HNC isomerization reaction. Although the results for this system are not
      very sensitive to the choice of coordinates, we find that the inclusion of
      anharmonicity leads to a substantial improvement in the vibrational energy
      levels. We also present detailed comparisons of rate constants computed with and
      without anharmonicity, with various approximations for incorporating tunneling
      along the reaction path, and with a more practical approach to calculating the
      vibrational partition functions needed for larger systems.

PMID- 16405309
TI  - Isotopic branching in (He, HD+) collisions.
AB  - A three-dimensional time-dependent quantum mechanical approach is used to
      calculate the reaction probability (P(R)) and the integral reaction cross section
      (sigma(R)) for both channels of the reaction He + HD+(v = 0, 1, 2, 3; j = 0) -->
      HeH(D)+ + D(H), over a range of translational energy (E(trans)) on two different
      ab initio potential energy surfaces (McLaughlin-Thompson-Joseph-Sathyamurthy and
      Palmieri et al.). The reaction probability plots as a function of translational
      energy exhibit several oscillations, which are characteristic of the system. The
      vibrational enhancement of the reaction probability and the integral reaction
      cross section values are reproduced qualitatively by our calculations, in
      accordance with the experimental results. The isotopic branching ratio for the
      reaction decreases in going from v = 0 to v = 1 and then becomes nearly v
      independent in going from v = 1 to v =3 on both the surfaces.

PMID- 16405310
TI  - Scaling dynamical correlation energy from density functional theory correlation
      functionals.
AB  - The scaling of dynamical correlation energy in molecules obtained by the
      correlation functionals of density functional theory (DFT) is examined. The
      approach taken is very similar to the scaled external correlation method of Brown
      and Truhlar but is based on the observation that DFT correlation functionals,
      especially the LYP, appear to represent the dynamical portion of the correlation
      energy in molecules. We examine whether higher accuracy in atomization energies
      can be gained by scaling without significant deterioration of the structural and
      spectroscopic properties of the molecules using four DFT functionals (BLYP, OLYP,
      B3LYP, and O3LYP) on 19 molecules including the six molecule AE6 database, the
      latter being representative of a much larger, 109 molecule training set. We show
      that, with molecule specific scale factors, nearly perfect agreement with
      experiment can be achieved in atomization energies without increasing the average
      errors in other molecular properties relative to the DFT calculation. We further
      show that it is possible to find optimal scale factors which reduce the mean
      unsigned error per bond to levels comparable to those of some multilevel
      multicoefficient methods.

PMID- 16405311
TI  - Ab initio MRD-CI study of the spectrum of the TeO molecule employing relativistic
      effective core potentials.
AB  - Potential energy curves and properties of the low-lying electronic states of
      tellurium oxide have been computed using a configuration interaction treatment
      that includes the spin-orbit coupling interaction. Relativistic effective core
      potentials (RECPs) are used to describe the inner shells of both the Te and O
      atoms. Good agreement is obtained for the spectroscopic constants of the X1
      X2(3)sigma-, a1delta, and b1sigma+ states for which experimental data are
      available. The ratio of the parallel and perpendicular b-X transition moments, as
      well as the radiative lifetime of the b state, was computed, and both results
      were also found to be in good agreement with measurement. The energetic order of
      the electronic states in TeO appears to be very similar to that observed for the
      isovalent O2 molecule, but the Rydberg valence-mixing effects that are so
      prominent in the latter's spectrum (e.g., for the Schumann-Runge bands) are
      totally absent in TeO.

PMID- 16405312
TI  - Modulation of fragmental charge transfer via hydrogen bonds. Direct measurement
      of electronic contributions.
AB  - Hydrogen bonds play an important role in an overwhelming variety of fields from
      biology to surface and supramolecular chemistry. The term "hydrogen bond" refers
      to a wide range of interactions with various covalent and polar contributions. In
      particular, hydrogen bonds have an important role in the folding and packing of
      peptides and nucleic acids. Recent studies also point to the importance of
      hydrogen bonding in the context of second-shell interactions, in metal binding
      and selectivity in metalloproteins, and in controlling the dynamics of membrane
      proteins. In this study, we demonstrate and quantify the modulation of fragmental
      charge transfer from hydrogen-bonded ligands to a metal center, by employing our
      recently introduced molecular potentiometer. The molecular details that affect
      this type of fragmental charge transfer are presented and a path for transferring
      chemical information is demonstrated. We found that H-bond interactions in the
      extended positions of axial ligands provide an effective means of modulating the
      amount of fragmental charge transfer to a metal center, thereby dramatically
      influencing the electronic properties of the ligand, the binding affinity, and
      the binding of additional ligands. The magnitude of fragmental charge-transfer
      modulation induced by a single ligand-solvent H-bond interaction is comparable to
      those induced by covalent substitution, although H-bond enthalpy is only on the
      order of several kilojoules per mole. Importantly, we find a significant change
      in the ligand electronic properties, even for weak C-H...O=C H-bond formation,
      where the bond enthalpy is substantially lower than for conventional H-bond
      interactions. The excess fragmental charge transferred to the metal center,
      deduced from the spectroscopic measurements, correlates well with the
      computationally determined values. Our findings underscore the importance of
      second-shell interactions in the active sites of enzymes, beyond the structural
      and electrostatic importance that is widely recognized today.

PMID- 16405313
TI  - A quasiclassical trajectory study of collisional energy transfer and dissociation
      in He + H2(v,j) using a new potential energy surface.
AB  - Quasiclassical trajectories for He + H2 were carried out using the recent ab
      initio potential of Boothroyd, Martin, and Peterson (J. Chem. Phys. 2003, 119,
      3187) and results for the 348 (v, j) states of H2 are compared to those of
      earlier calculations that used the potential of Wilson, Kapral, and Burns (Chem.
      Phys. Lett. 1974, 24, 4884). Examined are the cross sections for energy transfer
      and dissociation, the extent of threshold elevation, and the interconversion of
      vibrational and rotational energy. Implications for modeling the interstellar
      medium are discussed.

PMID- 16405314
TI  - Solubility of water in a benzene-cyclohexane mixture.
AB  - The solubility of a water molecule in a binary mixture of nonpolar cyclohexane
      and quadrupolar benzene is studied with the ab initio method. A novel self
      consistent reaction field theory that properly accounts for benzene quadrupole
      moments in the continuum solvent framework is used to describe the solvation
      effects of the solvent mixture. The free energy of transfer from pure cyclohexane
      to the mixture solvent is obtained with the neglect of nonelectrostatic
      contributions. A reasonable agreement with experiments indicates that the
      theoretical method presented here provides a promising approach to electronic
      structure calculations in quadrupolar solvents and their mixtures with nonpolar
      solvents.

PMID- 16405315
TI  - A simple picture for the rotational enhancement of the rate for the F + HCl -->
      HF + Cl reaction: a dynamical study using a new ab initio potential energy
      surface.
AB  - Quantum scattering calculations for the reaction F + HCl --> HF + Cl are
      performed on a new ground-state ab initio potential energy surface. The reagent
      rotation is found to have a dramatic effect on the reaction probability.
      Furthermore, the exit channel rotational thresholds leave a strong imprint on the
      reaction probabilities and even on the cumulative reaction probability. A very
      simple vibrationally adiabatic model is shown to account for most aspects of the
      reaction dynamics. In this model, the fast vibrational motion is adiabatically
      eliminated leaving the key reaction dynamics represented by a reduced atom +
      rotor collision. The shape of the adiabatic potential surface immediately yields
      to a simple and intuitive interpretation for the rotational enhancement of the
      rate. The rotational enhancement is shown to be an effect of the entrance channel
      dynamics of the atom-rotor problem.

PMID- 16405316
TI  - Ab initio potential energy and dipole moment surfaces of (H2O)2.
AB  - A full-dimensional ab initio potential energy surface (PES) and dipole moment
      surface (DMS) are reported for the water dimer, (H2O)2. The CCSD(T)-PES is a very
      precise fit to 19,805 ab initio energies obtained with the coupled-cluster
      (CCSD(T)) method, using an aug-cc-pVTZ basis. The standard counterpoise
      correction was applied to approximately eliminate basis set superposition errors.
      The fit is based on an approach that incorporates the permutational symmetry of
      identical atoms [Huang, X.; Braams, B.; Bowman, J. M. J. Chem.Phys. 2005, 122,
      044308]. The DMS is a fit to the dipole moment obtained with Moller-Plesset (MP2)
      theory, using an aug-cc-pVTZ basis. The PES has an RMS fitting error of 31 cm(-1)
      for energies below 20,000 cm(-1), relative to the global minimum. This surface
      can describe various internal floppy motions, including various monomer
      inversions, and isomerization pathways. Ten characteristic stationary points have
      been located on the surface, four of which are transition structures and the rest
      are higher order saddle points. Their geometrical and vibrational properties are
      presented and compared with available previous theoretical work. The CCSD(T)-PES
      and MP2-DMS dissociate correctly (and symmetrically) to two H2O monomers, with
      D(e) = 1665.7 cm(-1) (19.93 kJ/mol). Accurate quantum calculations of the zero
      point energy of the dimer (using diffusion Monte Carlo) and the monomers (using a
      vibrational configuration interaction approach) are reported, and these together
      with D(e) give a value of D0 of 1042 cm(-1) (12.44 kJ/mol). A best estimated
      value is 1130 cm(-1) (13.5 kJ/mol).

PMID- 16405317
TI  - Computational studies of the coordination stereochemistry, bonding, and metal
      selectivity of mercury.
AB  - Knowledge of the bonding and selectivity of organic mercury, [H3C-Hg]+ (MeHg+),
      and inorganic Hg2+ for protein and DNA functional groups is important for
      understanding the mechanism of heavy metal poisoning. Herein, we elucidate (1)
      the differences between inorganic Hg2+ and organic MeHg+ in their interactions
      with different ligands of biological interest, (2) the protein and DNA functional
      groups that Hg2+ and MeHg+ target in aqueous solution, and (3) the likelihood of
      "soft" Hg2+ displacing the "borderline" Zn2+ bound to "harder" nitrogen/oxygen
      containing side chains such as His and Asp/Glu. The results reveal that, relative
      to Hg2+, the lower positive charge on MeHg+ results in a longer and weaker bond
      with a given ligand, in accord with the observed kinetic lability of MeHg+
      complexes. They also indicate that negatively charged or polar amino acid side
      chains containing S-/O-/S/N donors could coordinate to both organic MeHg+ and
      inorganic Hg2+. In addition, Gua and Cyt could also coordinate to MeHg+ and
      disrupt Gua...Cyt base pairing. A key novel finding is that Hg2+ is a far better
      electron acceptor than Zn2+, and can thus accept more negative charge from the Zn
      ligands than the native Zn2+, thus enhancing Hg-ligand interactions and enabling
      Hg2+ to displace the native cofactor from zinc essential enzymes and "structural"
      Zn proteins. The results herein support several possible mechanisms for Hg
      poisoning. Ways that mercury poisoning could be prevented in cells are discussed.

PMID- 16405318
TI  - Insight into catalytically relevant correlated motions in human purine nucleoside
      phosphorylase.
AB  - The catalytic site of the homotrimeric enzyme human purine nucleoside
      phosphorylase enzyme (hPNP) features residue F200 and the 241-265 loop directly
      skirting the purine base and a residue belonging to the adjacent monomer, F159,
      immediately conterminous to the ribosyl moiety. Crystallographic B-factors of apo
      human purine nucleoside phosphorylase, and hPNP complexed with
      substrate/transition state (TS) analogues, show that residue E250 is the centroid
      of a highly mobile loop region. Furthermore, superimposition of apo hPNP and hPNP
      complexed with TS analogue Immucillin-H shows a tightening of the active site,
      caused by the ligand-dependent 241-265 loop rearrangement taking place upon
      substrate/inhibitor binding, suggesting a putative dynamic role of the loop in
      binding/catalysis. However, crystallographic structures reveal only average
      atomic positions, and more detailed information is needed to discern the dynamic
      behavior of hPNP. The Essential Dynamics (ED) method is used here to investigate
      the existence of correlated motions in hPNP and consequently proposes mutagenesis
      assays to estimate the relative importance of these motions in the phosphorolytic
      efficiency of the reaction catalyzed by hPNP. We compare the concerted motions
      obtained from multiple molecular dynamics simulations of apo and Michaelis
      complex of hPNP both in vacuo and in solution. The results of the principal
      component analysis for the apo hPNP indicate the existence of strong correlations
      predominantly in the vicinity of residue F159. However, for the Michaelis
      complex, concerted motions are seen mostly around both active site residue F200
      and loop residue E250. Additionally, for a simulation depicting the relaxation of
      tight complexed hPNP with a TS analogue, toward its relaxed apo form (after
      removal of the TS analog), a combination of the apo hPNP and Michaelis complex
      motions is found, with prominent concerted modes centered around neighboring
      residues F159, F200, and E250. Finally, we probed the extent to which these
      concerted motions bear an intrinsic catalytic role by performing experimental
      site-directed mutagenesis on some residues, followed by kinetic analysis. The
      F159G and F200G mutants displayed a strong increase in K(M) and modest decrease
      in k(cat), suggesting that these concerted motions may provide dynamical roles in
      substrate binding and/or catalysis. However, further structural data for the hPNP
      mutants are needed to confirm our hypothesis.

PMID- 16405319
TI  - Kinetics of the hydrogen abstraction OH + alkane --> H2O + alkyl reaction class:
      an application of the reaction class transition state theory.
AB  - This paper presents an application of the reaction class transition state theory
      (RC-TST) to predict thermal rate constants for hydrogen abstraction reactions of
      the type OH + alkane --> HOH + alkyl. We have derived all parameters for the RC
      TST method for this reaction class from rate constants of 19 representative
      reactions, coupling with linear energy relationships (LERs), so that rate
      constants for any reaction in this class can be predicted from its reaction
      energy calculated at either the AM1 semiempirical or BH&HLYP/cc-pVDZ level of
      theory. The RC-TST/LER thermal rate constants for selected reactions are in good
      agreement with those available in the literature. Detailed analyses of the
      results show that the RC-TST/LER method is an efficient method for accurately
      estimating rate constants for a large number of reactions in this class. Analysis
      of the LERs leads to the discovery of the beta-carbon radical stabilization
      effect that stabilizes the transition state of any reaction in this class that
      yields products having one or more beta-carbons, and thus leads to the lower
      barrier for such a reaction.

PMID- 16405320
TI  - New double many-body expansion potential energy surface for ground-state HCN from
      a multiproperty fit to accurate ab initio energies and rovibrational
      calculations.
AB  - An accurate single-sheeted double many-body expansion potential energy surface
      has been obtained for the ground electronic state of the hydrogen cyanide
      molecule via a multiproperty fit to ab initio energies and rovibrational data.
      This includes 106 rovibrational levels and 2313 discrete points, which are fit
      with a rmsd of 4 cm(-1) and 2.42 kcal mol(-1), respectively, and seven zero first
      derivatives that are reproduced at three stationary points. Since the potential
      also describes accurately the appropriate asymptotic limits at the various
      dissociation channels, it is commended both for the simulation of rovibrational
      spectra and reaction dynamics.

PMID- 16405321
TI  - Pseudo-two-dimensional structures (HXYH)3n2H6n (XY = GaN, SiC, GeC, SiSi, or
      GeGe; n = 1-3): density functional characterization of structures and energetics.
AB  - Hybrid density functional calculations with effective core potential basis sets
      are performed for monomeric group 13/15 and group 14/14 analogues of cyclohexane,
      as well as for three different pseudo-two-dimensional structures that can be
      formed from expanding one and two concentric rings around the central one (trans
      fused chairs, a rolling combination of trans- and cis-fused chairs, and cis-fused
      boats). Varying contributions from torsional strain, angle strain,
      electrostatics, and nontraditional H-H hydrogen bonding lead to different
      orderings and magnitudes of motif energies in the various systems: Homoatomic
      SiSi and GeGe systems prefer the trans-fused chair alternative and heteroatomic
      systems GaN, SiC, and GeC prefer the rolling chair. Decomposition of structure
      energies into characteristic fragment contributions indicates that pseudo-one
      dimensional rods of poly(imidogallane) are thermodynamically more stable than any
      of the pseudo-two-dimensional structures.

PMID- 16405322
TI  - Activation free energy of catechol O-methyltransferase. Corrections to the
      potential of mean force.
AB  - We use quantum mechanics/molecular mechanics (QM/MM) calculations to estimate the
      activation free energy for the chemical reaction catalyzed by catechol O
      methyltransferase. While in many cases the activation free energy of a chemical
      process is directly determined by the potential of mean force associated with a
      particular reaction coordinate, here we have included several corrections that
      have been proposed in the literature. These include the free energy change
      associated with release of the reaction coordinate motion in the reactant state,
      consideration of the curvilinear nature of the reaction coordinate, and
      correction due to the classical treatment of molecular vibrations. In addition,
      since potentials of mean force are usually obtained from low levels of QM theory
      to describe the quantum subsystem, we have included an interpolated correction
      term to improve this description at small additional cost. This last correction
      term has a dramatic effect, improving the agreement between the theoretical
      predictions and the experimental value, while the other terms considered make
      only small contributions to this particular reaction.

PMID- 16405323
TI  - Benzoderivatives of nucleic acid bases as modified DNA building blocks.
AB  - The tautomeric properties of benzoderivatives of the canonical nucleic acid bases
      have been studied by using different computational approaches. Attention has been
      paid to the impact of the benzene group in altering the tautomeric preferences of
      the canonical bases both in the gas phase and in aqueous solution. To this end,
      relative solvation free energies of the tautomers determined from Self-Consistent
      Reaction Field continuum calculations and Monte Carlo-Free Energy Perturbation
      are combined with gas-phase tautomerization free energies determined from quantum
      mechanical calculations. The results provide a detailed picture of the tautomeric
      preferences of the benzoderivatives of nucleic acid bases. This information is
      used to examine the recognition properties of the preferred tautomers of the
      benzo-fused derivatives, paying particular attention to the ability to form
      Watson-Crick hydrogen-bonding and stacking interactions as well as to the
      hydrophobic nature of the modified bases. The implications of present results on
      the potential use of benzo-fused bases as potential building blocks in modified
      DNA duplexes are examined.

PMID- 16405324
TI  - Modeling styrene-styrene interactions.
AB  - This study is the first step in the systematic investigation of substituted
      (carboxyl) polystyrene nanoparticles. Understanding the fundamental interactions
      between the p-carboxyl styrene monomers, where an ethyl group is used instead of
      a vinyl group (referenced, for convenience, as "p-carboxyl styrene"), provides
      the basic information needed to construct potentials for nanoparticles composed
      of these monomers. In this work, low-energy isomers of p-carboxyl styrene dimer
      were studied. The dimer structures and their relative and binding energies were
      determined using both Moller-Plesset second-order perturbation theory (MP2) and
      the general effective fragment potential (EFP2) method. Sections of the
      intermolecular potential energy surface (PES) of the p-carboxylated styrene dimer
      in its global minimum orientation were also determined. As expected, double
      hydrogen bonding between the two carboxylic groups provides the strongest
      interaction in this system, followed by isomers with a single H-bond and strong
      benzene ring-benzene ring (pi-pi) type interactions. Generally, the EFP2 method
      reproduces the MP2 geometries and relative energies with good accuracy, so it
      appears to be an efficient alternative to the correlated ab initio methods, which
      are too computationally demanding to be routinely used in the study of the more
      complex polymeric systems of interest.

PMID- 16405325
TI  - Dynamics and kinetics of heat transfer at the interface of model diamond [111]
      nanosurfaces.
AB  - A molecular dynamics simulation was performed to study the effect of an applied
      force on heat transfer at the interface of model diamond [111] nanosurfaces. The
      force was applied to a small, hot nanosurface at 800, 1000, or 1200 K brought
      into contact with a larger, colder nanosurface at 300 K. The relaxation of the
      initial nonequilibrium interfacial force occurs on a subpicosecond time scale,
      much shorter than that required for heat transfer. Heat transfer occurs with
      exponential kinetics and a rate constant that increases linearly with the
      interfacial force according to 7 x 10(-4) ps(-1)/nN. This rate constant only
      increases by at most 10% as the temperature of the hot surface is increased from
      800 to 1200 K. Replacing the interfacial H-atoms on both surfaces by D atoms also
      has a very small effect on the heat transfer. However, if one nanosurface has H
      atoms on its interface and the other nanosurface's interface has D atoms, then
      there is a marked 25% decrease in the rate constant for heat transfer. Increasing
      the size of the hot surface, and, thus, the interfacial contact area, increases
      the rate of heat transfer but not the rate constant. For the same interfacial
      force, different anharmonic models for the nanosurfaces' potential energy
      function give the same heat transfer rate constant. The possibility of quantum
      effects for heat transfer across the diamond interface is considered.

PMID- 16405326
TI  - Analytical potential energy surface describing abstraction reactions in
      asymmetrically substituted polyatomic systems of type CX3Y + A--> products.
AB  - The gas-phase reaction between chloromethane and hydrogen proceeds by two
      channels, Cl- and H-abstraction, and was chosen as a model of asymmetrically
      substituted polyatomic reactions of type CX3Y + A --> products. The analytical
      potential energy surface for this reaction was constructed with suitable
      functional forms to represent vibrational modes, and both channels were
      independently fitted to reproduce experimental and theoretical information only
      at the stationary points. The rate constants for the Cl- and H-channels and the
      overall reaction were calculated using variational transition-state theory with
      multidimensional tunneling effect over a wide temperature range, 298-3000 K. The
      Cl-abstraction reaction is preferred until 2100 K, while above this temperature
      the H-abstraction channel is favored. The theoretical overall rate constants
      agree with the experimental data in the common temperature range, 500-800 K, with
      a small curvature of the Arrhenius plot due mainly to the role of the tunneling
      in the H-abstraction channel. This surface was then used to analyze dynamical
      features, such as reaction-path curvature, and coupling between the reaction
      coordinate and vibrational modes. It was found qualitatively that excitation of
      the C-Cl and C-H stretching reactive modes enhances the forward rate constants
      for the Cl- and H-abstraction channels, respectively, and only the Cl-H and H-H
      stretching modes in the products of the Cl- and H-abstraction reactions,
      respectively, appear vibrationally excited.

PMID- 16405328
TI  - Transition-state energy and geometry, exothermicity, and van der Waals wells on
      the F + H2 --> FH + H ground-state surface calculated at the r12-ACPF-2 level.
AB  - Explicitly correlated averaged coupled-pair functional methods have been used to
      compute the ground-state Born-Oppenheimer potential energy surface for the F +
      HH' --> FH + H' reaction at the F + HH' and FH + H' asymptotes, the F...HH', and
      FH...H van der Waals wells, the reaction transition state, and at points along
      the intrinsic reaction coordinate connecting all of these stationary points. To
      these energies, corrections for spin-orbit coupling and scalar relativistic
      effects were added to produce total electronic energies whose accuracy is
      demonstrated to be very high (e.g., 0.1 kcal mol(-1)). The final data are used to
      refine the two-body parts of the currently best three-dimensional potential
      energy surface for this reaction, to predict several spectroscopic parameters of
      the species involved, and to offer accurate estimates of the title reaction's
      exothermicity (32.0 kcal mol(-1)) and activation barrier (1.8 kcal mol(-1)) as
      well as the geometry of the transition state.

PMID- 16405329
TI  - Systematic approach to understanding macrolide-ribosome interactions: NMR and
      modeling studies of oleandomycin and its derivatives.
AB  - The three-dimensional structures of oleandomycin (1) and its derivatives
      oleandomycin-9-oxime (2) and 10,11-anhydrooleandomycin (3) were determined in
      different solvents by the combined use of NMR and molecular modeling methods. The
      experimental NMR data were compared with the results of molecular modeling and
      known crystal structures of the related molecules. It was shown that the dominant
      conformation of the lactone ring is the folded-out conformation with some amounts
      of the folded-in one depending on the solvent and temperature, while desosamine
      and cladinose sugars adopt the usual chair conformations. Modeling calculations
      provided evidence for conformational changes in the upper lactone region as well.
      Saturation transfer difference (STD) NMR experiments have provided information on
      the binding epitopes of 1-3 in complexes with E. coli ribosomes. The obtained
      molecular surfaces in close contact with ribosomes were compared with recently
      available 3D structures of the related macrolide-ribosome complexes, and the
      observed differences were discussed. The knowledge gained from this study can
      serve as a platform for the design of novel macrolides with an improved
      biological profile.

PMID- 16405327
TI  - Toward theoretical analysis of long-range proton transfer kinetics in
      biomolecular pumps.
AB  - Motivated by the long-term goal of theoretically analyzing long-range proton
      transfer (PT) kinetics in biomolecular pumps, researchers made a number of
      technical developments in the framework of quantum mechanics-molecular mechanics
      (QM/MM) simulations. A set of collective reaction coordinates is proposed for
      characterizing the progress of long-range proton transfers; unlike previous
      suggestions, the new coordinates can describe PT along highly nonlinear three
      dimensional pathways. Calculations using a realistic model of carbonic anhydrase
      demonstrated that adiabatic mapping using these collective coordinates gives
      reliable energetics and critical geometrical parameters as compared to minimum
      energy path calculations, which suggests that the new coordinates can be
      effectively used as reaction coordinate in potential of mean force calculations
      for long-range PT in complex systems. In addition, the generalized solvent
      boundary potential was implemented in the QM/MM framework for rectangular
      geometries, which is useful for studying reactions in membrane systems. The
      resulting protocol was found to produce water structure in the interior of
      aquaporin consistent with previous studies including a much larger number of
      explicit solvent and lipid molecules. The effect of electrostatics for PT through
      a membrane protein was also illustrated with a simple model channel embedded in
      different dielectric continuum environments. The encouraging results observed so
      far suggest that robust theoretical analysis of long-range PT kinetics in
      biomolecular pumps can soon be realized in a QM/MM framework.

PMID- 16405330
TI  - Oxygen accessibility to ribonuclease a: quantitative interpretation of nuclear
      spin relaxation induced by a freely diffusing paramagnet.
AB  - The nuclear spin relaxation induced by a freely diffusing paramagnetic center
      provides a direct measure of intermolecular accessibility. A number of factors
      are involved in a quantitative interpretation of relaxation data including
      excluded volume effects, solvation differences, and the details of the electron
      spin relaxation in the paramagnetic center. In the case where the electron
      relaxation time is short compared with correlation times describing the electron
      nuclear coupling, the nuclear spin relaxation rates may be related to the
      effective local concentration of the paramagnetic center at different locations
      about the solute of interest. The local concentrations may in turn be related to
      differences in the local free energies of interaction between the diffusing
      paramagnet and the cosolute. We demonstrate this approach for the case of
      ribonuclease A and deduce surface free energy differences for a large number of
      protein proton sites. We find that the oxygen accessibility is poorly represented
      by hard-sphere models such as computed solvent or steric accessibility. There is
      a distribution of local intermolecular interactions with a width of the order of
      RT that dominates the report of the intermolecular exploration of the protein by
      this simple solute.

PMID- 16405331
TI  - Importance of anharmonicity, recrossing effects, and quantum mechanical tunneling
      in transition state theory with semiclassical tunneling. A test case: the H2 + Cl
      hydrogen abstraction reaction.
AB  - The hydrogen abstraction reaction from H2 by the Cl atom is studied by means of
      the variational transition state theory with semiclassical tunneling coefficients
      on the BW2 potential energy surface. Vibrational anharmonicity and coupling
      between the bending modes are taken into account. The occurrence of trajectories
      that recross the transition state is estimated by means of the canonical unified
      statistical method and by classical trajectories calculations. Different
      semiclassical methods for tunneling calculations are tested. Our results show
      that anharmonicity has a small but nonnegligible effect on the thermal rate
      constants, recrossing can be neglected, and tunneling is adequately described by
      the least-action approximation, and less successfully by the large-curvature
      version 3 approximation. However, the large-curvature version 4 and small
      curvature approximations lead to a severe underestimation of tunneling. Thermal
      rate constants calculated using transition state theory including anharmonicity
      and tunneling agree very well with accurate quantal thermal rate constants over a
      wide temperature range, although the improvement over the harmonic transition
      state theory with the microcanonically optimized semiclassical tunneling
      approximation (based on version 3 of the large-curvature tunneling method) used
      in a previous study of this reaction is only marginal.

PMID- 16405332
TI  - Dynamics of the concerted triple proton transfer in cyclic water trimer using the
      multiconfiguration molecular mechanics algorithm.
AB  - Cyclic water clusters are important molecular species to understand the nature of
      hydrogen bonded networks. Theoretical studies for the dynamics of triple proton
      transfer in the cyclic water trimer were performed. The potential energy surface
      (PES) of triple proton transfer is generated by the multiconfiguration molecular
      mechanics (MCMM) algorithm. We have used the MP2/6-31G(d,p) level for high-level
      ab initio data (energies, gradients, and Hessians), which are used in the Shepard
      interpolation. Eight high-level reference points were added step by step,
      including two points for the critical configurations of the large curvature
      tunneling paths. The more high-level points are used, the better the potential
      energy surfaces become. The rate constant and kinetic isotope effect (KIE) for
      the triple proton transfer at 300 K, which have been calculated by the canonical
      variational transition-state theory with microcanonical optimized
      multidimensional semiclassical tunneling approximation, are 1.6 x 10(-3) s(-1)
      and 230, respectively. Tunneling is very important not only for the triple proton
      transfer but also for the triple deuterium transfer. The MCMM results show good
      agreement with those from the direct ab initio dynamics calculations.

PMID- 16405333
TI  - Oxygen interstitials in superconducting La2CuO4: their valence state and role.
AB  - The nature of the much debated valence state of an interstitial oxygen atom in
      oxygen-doped La2CuO4 is the subject of this paper. In model cluster calculations,
      we studied the position, charge, and spin state of the interstitial oxygen atoms
      in this superconductor. The models considered allow the interstitial oxygen to
      move off a symmetrical position, to have varying spin and charge, and to be
      surrounded by various magnetic environments. UB3LYP calculations show that a
      model having an interstitial oxygen atom with a total spin of 1 is lowest in
      energy; the interstitial oxygen atoms here act as stable radicals with a net
      charge of -1. These results agree with experimental evidence for the paramagnetic
      behavior for interstitial atoms. The energy associated with a spin flip at a Cu
      site in our models is lower if interstitial oxygen has a local electron spin
      density, compared to the case when it does not. We provide a possible explanation
      for the increase of the doping concentrations of interstitial oxygen with a
      decrease of the Neel temperature of this system. The relative stability of the
      models we consider depends on their spin states, accompanied by structural
      changes; this explains indirectly the experimental change of the slope (from 2 to
      1.3) of the linear relationship between the hole concentration and the oxygen
      content. Our results support a stripe phase in high temperature
      superconductivity; in our calculations, hole doping to the copper oxide layer
      comes only through the formation of an oxygen interstitial pair, not from any
      change of the local structural environment and magnetic field around the single
      interstitial.

PMID- 16405334
TI  - Ab initio molecular dynamics of excited-state intramolecular proton transfer
      around a three-state conical intersection in malonaldehyde.
AB  - Excited-state potential energy surface (PES) characterization is carried out at
      the CASSCF and MRSDCI levels, followed by ab initio dynamics simulation of
      excited-state intramolecular proton transfer (ESIPT) on the S2(pipi*) state in
      malonaldehyde. The proton-transfer transition state lies close to an S2/S1
      conical intersection, leading to substantial coupling of proton transfer with
      electronic relaxation. Proton exchange proceeds freely on S2, but its duration is
      limited by competition with twisting out of the molecular plane. This
      rotamerization pathway leads to an intersection of the three lowest singlet
      states, providing the first detailed report of ab initio dynamics around a three
      state intersection (3SI). There is a significant energy barrier to ESIPT on S1,
      and further pyramidalization of the twisted structure leads to the minimal energy
      S1/S0 intersection and energetic terminal point of excited-state dynamics.
      Kinetics and additional mechanistic details of these pathways are discussed.
      Significant depletion of the spectroscopic state and recovery of the ground state
      is seen within the first 250 fs after photoexcitation.

PMID- 16405335
TI  - A multistate empirical valence bond description of protonatable amino acids.
AB  - The multistate empirical valence bond (MS-EVB) model, which was developed for
      molecular dynamics simulations of proton transport in water and biomolecular
      systems, is extended for the modeling of protonatable amino acid residues in
      aqueous environments, specifically histidine and glutamic acid. The parameters of
      the MS-EVB force field are first determined to reproduce the geometries and
      energetics of the gas phase amino acid-water clusters. These parameters are then
      optimized to reproduce experimental pK(a) values. The free energy profiles for
      acid ionization and the corresponding pK(a) values are calculated by MS-EVB
      molecular dynamics simulations utilizing the umbrella sampling technique, with
      the center of excess charge coordinate chosen as the dissociation reaction
      coordinate. A general procedure for fitting the MS-EVB parameters is formulated,
      which allows for the parametrization of other amino acid residues with
      protonatable groups and the subsequent use of the MS-EVB approach for molecular
      dynamics simulations of proton transfer processes in proteins involving
      protonation/deprotonation of the protonatable amino acid groups.

PMID- 16405336
TI  - Simulating fluid-phase equilibria of water from first principles.
AB  - Efficient Monte Carlo algorithms and a mixed-basis set electronic structure
      program were used to compute from first principles the vapor-liquid coexistence
      curve of water. A water representation based on the Becke-Lee-Yang-Parr exchange
      and correlation functionals yields a saturated liquid density of 900 kg/m3 at 323
      K and normal boiling and critical temperatures of 350 and 550 K, respectively. An
      analysis of the structural and electronic properties of the saturated liquid
      phase shows an increase of the asymmetry of the local hydrogen-bonded structure
      despite the persistence of a 4-fold coordination and decreases of the molecular
      dipole moment and of the spread of the lowest unoccupied molecular orbital with
      increasing temperature.

PMID- 16405337
TI  - Conformational landscape of (R,R)-pterocarpans with biological activity in vacuo
      and in aqueous solution (PCM and/or water clusters).
AB  - All possible combinations of stable dihedral values have been considered in vacuo
      at the B3LYP/6-31G level for 3,9-dihydroxy-4,8-diprenylpterocarpan (erybraedin
      C), whose hydroxy out-out conformation had been examined earlier together with
      the conformational preferences of 3,9-dimethoxy-4-prenylpterocarpan (bitucarpin
      A) at the same level (Phys. Chem. Chem. Phys. 2004, 6, 2849). The structure with
      O5 trans with respect to H6a (O(t)) is about 2 kcal/mol less stable in vacuo than
      that with one of the H6 trans to it (H(t)); in aqueous solution its energy gap is
      nearly conserved. The in-in arrangement of the hydroxyl groups of erybraedin
      turns out to be preferred in vacuo (even considering zero point and thermal
      effects), where pseudo H-bonds are formed between hydroxy hydrogens and pi
      electron distributions of prenyl groups. The continuum solvent effect (water) at
      the IEF-PCM/B3LYP/6-31G level on the relative stability of the various rotamers
      is very limited both on bitucarpin and erybraedin. Considering the dihydrated
      derivatives, significant differences in the solvation energy are found between
      the distinct hydration sites, increasing in the order: methoxy O, ring O, hydroxy
      O, and hydroxy H. In hydroxy-water interactions, in fact, water prefers to behave
      as an H-bond acceptor unless nearby bulky groups prevent its approach.
      Interestingly enough, a bridging water molecule between the hydroxy H of
      erybraedin and the prenyl group can be found. The inclusion of BSSE corrections
      in hydroxy-water interactions decidedly favors out-out hydrated arrangements,
      followed by out-in and in-out ones. Bulk solvent effects with IEF-PCM about the
      dihydrated systems almost invert the stability order found in vacuo. When a four
      water cluster is considered using QM methods, waters gather in H-bonded pairs
      around the solute OH groups. MD simulations, carried out on a pterocarpan solute
      (J. Phys. Chem. B 2005, 109, 16918), supply water adducts consistent with a
      liquid state that have also been embedded in the continuum solvent.

PMID- 16405338
TI  - Uptake of phenol on aerosol particles.
AB  - We present a study of the interaction between a phenol molecule and an aerosol
      particle. The aerosol particle is represented by a cluster of 128 water
      molecules. Using a classical approach, we present interaction energy surfaces for
      different relative distances and for three orientations of phenol relative to the
      particle. From the energy surfaces we find the reaction pathways with the largest
      interaction between the molecule and the particle. We use a quantum
      mechanics/molecular mechanics (QM/MM) method to calculate a potential energy
      curve for each reaction path. Coupled cluster methods are used for the part of
      the system described by quantum mechanics, while the part described by molecular
      mechanics is represented by a polarizable force field. We compare results
      obtained from the classical approach with the QM/MM results. Furthermore, we use
      the QM/MM results to calculate mass accommodation coefficients using a quantum
      statistical (QM-ST) model and show how the mass accommodation coefficient depends
      on the relative orientation of phenol with respect to the aerosol particle.

PMID- 16405339
TI  - Effect of finite size on cooperativity and rates of protein folding.
AB  - We analyze the dependence of cooperativity of the thermal denaturation transition
      and folding rates of globular proteins on the number of amino acid residues, N,
      using lattice models with side chains, off-lattice Go models, and the available
      experimental data. A dimensionless measure of cooperativity, Omega(c) (0 <
      Omega(c) < infinity), scales as Omega(c) approximately N(zeta). The results of
      simulations and the analysis of experimental data further confirm the earlier
      prediction that zeta is universal with zeta = 1 + gamma, where exponent gamma
      characterizes the susceptibility of a self-avoiding walk. This finding suggests
      that the structural characteristics in the denaturated state are manifested in
      the folding cooperativity at the transition temperature. The folding rates k(F)
      for the Go models and a dataset of 69 proteins can be fit using k(F) = k(F)0 exp(
      cN(beta)). Both beta = 1/2 and 2/3 provide a good fit of the data. We find that
      k(F) = k(F)0 exp(-cN(1/2)), with the average (over the dataset of proteins) k(F)0
      approximately (0.2 micros)(-1) and c approximately 1.1, can be used to estimate
      folding rates to within an order of magnitude in most cases. The minimal models
      give identical N dependence with c approximately 1. The prefactor for off-lattice
      Go models is nearly 4 orders of magnitude larger than the experimental value.

PMID- 16405341
TI  - Novel diborane-analogue transition structures for borane reactions with alkyl
      halides.
AB  - Ab initio and DFT calculations were performed to examine the mechanisms of
      reduction of alkyl halides and formaldehyde by borane. With alkyl halides, the
      optimized transition structure geometry resembled diborane, with a pair of
      hydrogen atoms bridging the boron and carbon atoms by three-center-two-electron
      bonds. A similar transition structure was found for the reduction of
      formaldehyde, although it was not the lowest-energy transition structure.
      Solvation by dimethyl ether or dimethyl sulfide disrupted this bridging with
      chloromethane, while both ligands dissociated from borane during the reduction of
      formaldehyde. The high calculated activation free energies of alkyl halide
      reduction are consistent with their observed lack of reactivity with borane.

PMID- 16405340
TI  - H + CD4 abstraction reaction dynamics: excitation function and angular
      distributions.
AB  - We compare experimental photoloc measurements and quasi-classical trajectory
      calculations of the integral cross sections, lab-frame speed distributions, and
      angular distributions associated with the CD3 products of the H + CD4(nu = 0) -->
      CD3 + HD reaction at collision energies ranging from 0.5 to 3.0 eV. Of the
      potential energy surfaces (PES) we explored, the direct dynamics calculations
      using the B3LYP/6-31G** density functional theory PES provide the best agreement
      with the experimental measurements. This agreement is likely due to the better
      overall description that B3LYP provides for geometries well removed from the
      minimum energy path, even though its barrier height is low by approximately 0.2
      eV. In contrast to previous theoretical calculations, the angular distributions
      on this surface show behavior associated with a stripping mechanism, even at
      collision energies only approximately 0.1 eV above the reaction barrier. Other
      potential energy surfaces, which include an analytical potential energy surface
      from Espinosa-Garcia and a direct dynamics calculation based on the MSINDO
      semiempirical Hamiltonian, are less accurate and predict more rebound dynamics at
      these energies than is observed. Reparametrization of the MSINDO surface, though
      yielding better agreement with the experiment, is not sufficient to capture the
      observed dynamics. The differences between these surfaces are interpreted using
      an analysis of the opacity functions, where we find that the wider cone of
      acceptance on the B3LYP surface plays a crucial role in determining the integral
      cross sections and angular distributions.

PMID- 16405342
TI  - Empirical force fields for biologically active divalent metal cations in water.
AB  - We have presented a strategy for deriving ion-water van der Waals (vdW)
      parameters that implicitly include the microscopic solvent molecular effects
      around the ion. The strategy can be used to obtain vdW parameters for metal
      cations of the same formal charge and known experimental hydration free energies.
      In this work, it was applied to derive the vdW parameters for 24 divalent metal
      ions with measured hydration free energies ranging from -300 to -572 kcal/mol,
      coordination numbers (CNs) from 4 to 15, and ion-O (water) distances from 1.67 to
      2.90 angstroms. The strategy used to derive the vdW parameters employs (1) a
      numerical procedure that links the coupling parameter used in free energy
      simulations with the experimental hydration free energies and (2) the first-shell
      CNs and structure for the entire series of divalent cations. One of the parameter
      sets obtained (referred to as MWc) simultaneously reproduces the observed (i)
      relative hydration free energies, (ii) first-shell CNs, and (iii) average ion
      water distances of all the dications studied. In particular, the MWc parameters
      reproduce the observed (i) decrease in the CN from 6 for Cu2+ to 4 for Be2+, (ii)
      no change in the CN of 6 for dications with hydration free energies between those
      of Cu2+ and Cd2+, and (iii) an expansion of the CN from 6 for Cd2+ to 9.5 for
      Ba2+. The ion-water parameters derived herein represent a first step in the
      simulations of metalloproteins, which will also require potential energy
      functions incorporating polarizability, charge transfer, and other electronic
      effects to accurately model the protein-metal interactions in aqueous solution.

PMID- 16405343
TI  - Theoretical and experimental determination on two substrates turned over by 4
      oxalocrotonate tautomerase.
AB  - Quantum mechanical/molecular mechanical (QM/MM) calculations and experimental
      kinetic studies have been performed on 4-oxalocrotonate tautomerase (4OT) for two
      different substrates, 2-hydroxymuconate (2HM) and 2-oxo-4-hexenedioate (2o4hex).
      Potential (deltaE) and free energy (deltaG) paths for both steps of the reaction
      using both substrates were calculated to determine the free energy barriers and
      compared to the experimental values obtained from the kinetic studies via the
      transition state theory. In the first step, a proton from the hydroxyl oxygen on
      the second carbon of 2HM, or from the third carbon of 2o4hex, is abstracted by
      Pro-1. In the second step, the proton is transferred to the fifth carbon of the
      substrate to form the product, 2-oxo-3-hexenedioate (2o3hex). For both substrates
      we obtain a calculated deltaG of approximately 13 kcal/mol, in agreement with
      experimental determinations. The calculated free energy barrier difference
      deltaG2o4hex - deltaG2HM (deltadeltaG) is 0.87 kcal/mol. We obtained an
      experimental deltadeltaG of 0.85 kcal/mol. These results suggest that 2HM is
      turned over faster than 2o4hex by 4OT. However, these energy differences are so
      small that both 2HM and 2o4hex need to be taken into account in considering the
      mechanism of catalysis of 4OT.

PMID- 16405344
TI  - Benchmark study of DFT functionals for late-transition-metal reactions.
AB  - The performance of a wide variety of DFT exchange-correlation functionals for a
      number of late-transition-metal reaction profiles has been considered. Benchmark
      ab-initio reference data for the prototype reactions Pd + H2, Pd + CH4, Pd + C2H6
      (both C-C and C-H activation), and Pd + CH3Cl are presented, while ab-initio data
      of lesser quality were obtained for the catalytic hydrogenation of acetone and
      for the low-oxidation-state and high-oxidation-state mechanisms of the Heck
      reaction. "Kinetics" functionals such as mPW1K, PWB6K, BB1K, and BMK clearly
      perform more poorly for late-transition-metal reactions than for main-group
      reactions, as well as compared to general-purpose functionals. There is no single
      "best functional" for late-transition-metal reactions, but rather a cluster of
      several functionals (PBE0, B1B95, PW6B95, and TPSS25B95) that perform about
      equally well; if main-group thermochemical performance is additionally
      considered, then B1B95 and PW6B95 emerge as the best performers. TPSS25B95 and
      TPSS33B95 offer attractive performance compromises if weak interactions and main
      group barrier heights, respectively, are also important. In the ab-initio
      calculations, basis set superposition errors (BSSE) can be greatly reduced by
      ensuring that the metal spd shell has sufficient radial flexibility in the high
      exponent range. Optimal HF percentages in hybrid functionals depend on the class
      of systems considered, increasing from anions to neutrals to cations to main
      group barrier heights; transition-metal barrier heights represent an intermediate
      situation. The use of meta-GGA correlation functionals appears to be quite
      beneficial.

PMID- 16405345
TI  - On the ionization state of the substrate in the active site of glutamate
      racemase. A QM/MM study about the importance of being zwitterionic.
AB  - Computer simulations on a QM/MM potential energy surface have been carried out to
      gain insights into the catalytic mechanism of glutamate racemase (MurI).
      Understanding such a mechanism is a challenging task from the chemical point of
      view because it involves the deprotonation of a low acidic proton by a relatively
      weak base to give a carbanionic intermediate. First, we have examined the
      dependency of the kinetics and thermodynamics of the racemization process
      catalyzed by MurI on the ionization state of the substrate (glutamate) main
      chain. Second, we have employed an energy decomposition procedure to study the
      medium effect on the enzyme-substrate electrostatic and polarization interactions
      along the reaction. Importantly, the present theoretical results quantitatively
      support the mechanistic proposal by Rios et al. [J. Am. Chem. Soc. 2000, 122,
      9373-9385] for the PLP-independent amino acid racemases.

PMID- 16405346
TI  - Stereoselectivity behavior of the AZ28 antibody catalyzed oxy-Cope rearrangement.
AB  - Catalytic antibodies are very interesting not only because of the rate
      enhancement of the reactions that they catalyze but also because of the
      selectivities they can achieve that are sometimes not present in natural enzyme
      processes. We have selected the study of the stereoselectivity of the matured
      AZ28 that catalyzes an oxy-Cope rearrangement. For this particular case, the
      presence of a chiral center in the substrate provokes the existence of two
      different enantiomers, R and S. Furthermore, it is also possible to locate two
      different orientations for the hydroxyl group in the central ring of the
      substrate in the transition state, equatorial and axial, rendering two different
      conformers. In this paper we present the free energy profiles obtained for
      different substrate isomers in the cavity created by the matured catalytic
      antibody. Our simulations have reproduced the stereoselectivity of the matured
      AZ28, differentiating between the axial or equatorial orientations and
      preferentially stabilizing the S forms, at a qualitative level. Finally, the
      inclusion of the substrate-CA interactions in a flexible molecular model has
      allowed us to observe the different pattern of interactions that are related to
      different interaction energies, which seem to be crucial in the stereoselectivity
      behavior of the catalytic antibody.

PMID- 16405347
TI  - Quantum simulation of a hydrated noradrenaline analog with the torsional path
      integral method.
AB  - An extended version of the torsional path integral Monte Carlo (TPIMC) method is
      presented and shown to be useful for studying the conformation of flexible
      molecules in solvated clusters. The new technique is applied to the hydrated
      clusters of the 2-amino-1-phenyl-ethanol (APE) molecule. APE + nH2O clusters with
      n = 0-4 are studied at 100 and 300 K using both classical and quantum
      simulations. Only at the lower temperature is the hydration number n found to
      impact the conformational distribution of the APE molecule. This is shown to be a
      result of the temperature-dependent balance between the internal energy and
      entropy contributions to the relative conformer free energies. Furthermore, at
      100 K, large quantum effects are observed in the calculated conformer
      populations. A particularly large quantum shift of 30% of the total population is
      calculated for the APE + 2H2O cluster, which is explained in terms of the
      relative zero point energy of the lowest-energy hydrated structures for this
      cluster. Finally, qualitative agreement is found between the reported
      calculations and recent spectroscopy experiments on the hydrated clusters of APE,
      including an entropically driven preference for the formation of AG-type hydrated
      structures and the formation of a water "droplet" in the APE + 4H2O cluster.

PMID- 16405348
TI  - Theory of time-dependent reactive scattering: cumulative time-evolving
      differential cross sections and nearside-farside analyses of time-dependent
      scattering amplitudes for the H + D2 --> HD + D reaction.
AB  - Nearside-farside (NF) theory, originally developed in the energy domain for the
      time-independent description of molecular collisions and chemical reactions, is
      applied to the plane wave packet (PWP) formulation of time-dependent scattering.
      The NF theory decomposes the partial wave series representation for the time
      dependent PWP scattering amplitude into two time-dependent subamplitudes: one N,
      the other F. In addition, NF local angular momentum (LAM) theory is applied to
      the PWP scattering amplitude. The novel concept of a cumulative time-evolving
      differential cross section is introduced, in which the upper infinite time limit
      of a half-Fourier transform is replaced by a finite time. In a similar way, a
      cumulative energy-evolving angular distribution is defined. Application is made
      to the state-to-state reaction, H + D2(v(i) = 0, j(i) = 0) --> HD(v(f) = 3, j(f)
      = 0) + D, where v(i), j(i) and v(f), j(f) are vibrational and rotational quantum
      numbers for the initial and final states, respectively. This reaction exhibits
      time-direct and time-delayed (by about 25 fs) collision mechanisms. It is shown
      that the direct-time mechanism is N dominant scattering, whereas the time-delayed
      mechanism exhibits characteristics of NF interference. The NF and LAM theories
      provide valuable insights into the time-dependent properties of a reaction, as do
      snapshots from a movie of the cumulative time-evolving differential cross
      section.

PMID- 16405349
TI  - Density matrix treatment of the nonmarkovian dissipative dynamics of adsorbates
      on metal surfaces.
AB  - A density matrix treatment is presented for the vibrational relaxation of the
      frustrated translational mode of a molecule adsorbed on a metal surface. The
      system is modeled as a vibrating adsorbate oscillator coupled to a bath of
      harmonic oscillators representing either phonons or electronic density
      fluctuations. The integrodifferential equations for time evolution of the density
      matrix including a (nonmarkovian) delayed dissipation are solved using a
      generalized Runge-Kutta scheme. The equations are also solved in the
      instantaneous dissipation and the Markov limits, to ascertain their validity.
      Numerical results are presented for Na/Cu, CO/Cu, and CO/Pt systems. The
      population of an initially excited state is given over time for varying
      temperatures and shows that memory effects are needed in a proper description
      valid even at short times. Calculations of populations for different coupling
      strengths between the adsorbate species and the substrate metal surface indicate
      that a weaker coupling leads to increased oscillation amplitudes and longer
      relaxation times. The time evolution of quantum coherence is also described.

PMID- 16405350
TI  - Analysis of the reaction force for a gas phase S(N)2 process: CH3Cl + H2O -->
      CH3OH + HCl.
AB  - The "reaction force" F(R(c)) is the negative derivative of a system's potential
      energy V(R(c)) along the intrinsic reaction coordinate of a process. If V(R(c))
      goes through a maximum, as is commonly the case, then F(R(c)) has a
      characteristic profile: a negative minimum followed by zero at the transition
      state and then a positive maximum. These features reflect four phases of the
      reaction: an initial one of reactant preparation, followed by two of transition
      to products, and then relaxation of the latter. In this study, we have analyzed,
      in these terms, a gas-phase S(N)2 substitution, selected to be CH3Cl + H2O -->
      CH3OH + HCl. We examine, at the B3LYP/6-31G level, the geometries, energetics,
      and molecular surface electrostatic potentials, local ionization energies, and
      internal charge separation.

PMID- 16405351
TI  - Sensitivity analysis of thermodynamic properties of liquid water: a general
      approach to improve empirical potentials.
AB  - A sensitivity analysis of bulk water thermodynamics is presented in an effort to
      understand the relation between qualitative features of molecular potentials and
      properties that they predict. The analysis is incorporated in molecular dynamics
      simulations and investigates the sensitivity of the Helmholtz free energy,
      internal energy, entropy, heat capacity, pressure, thermal pressure coefficient,
      and static dielectric constant to components of the potential rather than the
      parameters of a given functional form. The sensitivities of the properties are
      calculated with respect to the van der Waals repulsive and the attractive parts,
      plus short- and long-range Coulomb parts of three four site empirical water
      potentials: TIP4P, Dang-Chang and TTM2R. The polarization sensitivity is
      calculated for the polarizable Dang-Chang and TTM2R potentials. This new type of
      analysis allows direct comparisons of the sensitivities for different potentials
      that use different functional forms. The analysis indicates that all investigated
      properties are most sensitive to the van der Waals repulsive, the short-range
      Coulomb and the polarization components of the potentials. When polarization is
      included in the potentials, the magnitude of the sensitivity of the Helmholtz
      free energy, internal energy, and entropy with respect to this part of the
      potential is comparable in magnitude to the other electrostatic components. In
      addition similarities in trends of observed sensitivities for nonpolarizable and
      polarizable potentials lead to the conclusion that the complexity of the model is
      not of critical importance for the calculation of these thermodynamic properties
      for bulk water. The van der Waals attractive and the long-range Coulomb
      sensitivities are relatively small for the entropy, heat capacity, thermal
      pressure coefficient and the static dielectric constant, while small changes in
      any of the potential contributions will significantly affect the pressure. The
      analysis suggests a procedure for modification of the potentials to improve
      predictions of thermodynamic properties and we demonstrate this general approach
      for modifying potentials for one of the potentials.

PMID- 16405353
TI  - Behavior of density functionals with respect to basis set. 3. Basis set
      superposition error.
AB  - The impact of basis set superposition error (BSSE) upon molecular properties
      determined using the density functionals B3LYP, B3PW91, B3P86, BLYP, BPW91, and
      BP86 in combination with the correlation consistent basis sets [cc-pVnZ, where n
      = D(2), T(3), Q(4), and 5] for a set of first-row closed-shell molecules has been
      examined. Correcting for BSSE enables the irregular convergence behavior in
      molecular properties such as dissociation energies with respect to increasing
      basis set size, noted in earlier studies, to be improved. However, for some
      molecules and functional combinations, BSSE correction alone does not improve the
      irregular convergence behavior.

PMID- 16405352
TI  - Multicoordinate driven method for approximating enzymatic reaction paths:
      automatic definition of the reaction coordinate using a subset of chemical
      coordinates.
AB  - We present a generalization of the reaction coordinate driven method to find
      reaction paths and transition states for complicated chemical processes,
      especially enzymatic reactions. The method is based on the definition of a subset
      of chemical coordinates; it is simple, robust, and suitable to calculate one or
      more alternative pathways, intermediate minima, and transition-state geometries.
      Though the results are approximate and the computational cost is relatively high,
      the method works for large systems, where others often fail. It also works when a
      certain reaction path competes with others having a lower energy barrier.
      Accordingly, the procedure is appropriate to test hypothetical reaction
      mechanisms for complicated systems and provides good initial guesses for more
      accurate methods. We present tests on a number of simple reactions and on several
      complicated chemical transformations and compare the results with those obtained
      by other methods. Calculation of the reaction path for the enzymatic hydrolysis
      of the substrate by dUTPase for an active-site model with 85 atoms, including
      several loosely bound water molecules, indicates that the method is feasible for
      the study of enzyme mechanisms.

PMID- 16405354
TI  - Structure and redox properties of the protein, rubredoxin, and its ligand and
      metal mutants studied by electronic structure calculation.
AB  - The changes in the structural and electronic properties accompanying metal
      ionization of the iron-containing protein, rubredoxin, and of some ligand and
      metal mutants, have been explored using density functional theory (DFT)
      calculations of the metal atom coordinated to the four immediate residues. Both
      isolated and embedded cluster studies have been carried out, the latter using the
      hybrid quantum mechanics/molecular mechanics (QM/MM) approach. The replacement of
      a cysteine by a serine residue has a considerable effect on both the electronic
      and geometric structure of the core, which can be qualitatively understood on the
      basis of the isolated cluster studies. The modulation of these properties caused
      by the protein environment is quite accurately described by the QM/MM
      calculations. The predicted core geometries are in good accord with both X-ray
      and EXAFS data, and the changes in the redox potentials are predicted, at least
      semiquantitatively, by considering only the core part of the protein.

PMID- 16405355
TI  - Multilevel and density functional electronic structure calculations of proton
      affinities and gas-phase basicities involved in biological phosphoryl transfer.
AB  - Five multilevel model chemistries (CBS-QB3, G3B3, G3MP2B3, MCG3/3, and MC
      QCISD/3) and seven hybrid density functional methods (PBE0, B1B95, B3LYP,
      MPW1KCIS, PBE1KCIS, and MPW1B95) have been applied to the calculation of gas
      phase basicity and proton affinity values for a series of 17 molecules relevant
      to the study of biological phosphoryl transfer. In addition, W1 calculations were
      performed on a subset of molecules. The accuracy of the methods was assessed and
      the nature of systematic errors was explored, leading to the introduction of a
      set of effective bond enthalpy and entropy correction terms. The multicoefficient
      correlation methods (MCG3/3 and MC-QCISD), with inclusion of specific zero-point
      scale factors, slightly outperform the other multilevel methods tested (CBS-QB3,
      G3B3, and G3MP2B3), with significantly less computational cost, and in the case
      of MC-QCISD, slightly less severe scaling. Four density functional methods,
      PBE1KCIS, MPW1B95, PBE0, and B1B95 perform nearly as well as the multilevel
      methods. These results provide an important set of benchmarks relevant to
      biological phosphoryl transfer reactions.

PMID- 16405356
TI  - Variational transition-state theory study of the dimethyl sulfoxide (DMSO) and OH
      reaction.
AB  - The mechanism for the atmospheric oxidation of DMSO has been studied. For the
      first time, all the possible channels in the DMSO + OH reaction are studied
      together theoretically, and their corresponding rate constants have been
      evaluated under the variational transition-state formalism. Three different
      channels have been characterized: an addition-elimination process to form MSIA
      (CH3SOOH) and CH3, a H-abstraction pathway to give CH3SOCH2 and H2O, and a
      nonkinetically relevant S(N)2-type reaction to form methanol and CH3SO. In
      agreement with previous experimental and theoretical works, the main product in
      the DMSO + OH reaction turns out to be the MSIA, with a branching ratio at 298.15
      K around 97%. The effects of pressure in the global rate constant have also been
      analyzed.

PMID- 16405357
TI  - Incorporating the geometric phase effect in triatomic and tetraatomic
      hyperspherical harmonics.
AB  - Hyperspherical harmonics in the democratic row-orthonormal hyperspherical
      coordinates are very appropriate basis sets for performing reactive scattering
      calculations for triatomic and tetraatomic systems. The mathematical conditions
      for incorporating the geometric phase effect in these harmonics are given. These
      conditions are implemented for triatomic systems, and their explicit analytical
      expressions in terms of Jacobi polynomials, in both the absence and presence of
      the geometric phase effect, are given.

PMID- 16405358
TI  - Experimental and theoretical differential cross sections for the N(2D) + H2
      reaction.
AB  - In this paper, we report a combined experimental and theoretical study on the
      dynamics of the N(2D) + H2 insertion reaction at a collision energy of 15.9 kJ
      mol(-1). Product angular and velocity distributions have been obtained in crossed
      beam experiments and simulated by using the results of quantum mechanical (QM)
      scattering calculations on the accurate ab initio potential energy surface (PES)
      of Pederson et al. (J. Chem. Phys. 1999, 110, 9091). Since the QM calculations
      indicate that there is a significant coupling between the product angular and
      translational energy distributions, such a coupling has been explicitly included
      in the simulation of the experimental results. The very good agreement between
      experiment and QM calculations sustains the accuracy of the NH2 ab initio ground
      state PES. We also take the opportunity to compare the accurate QM differential
      cross sections with those obtained by two approximate methods, namely, the widely
      used quasiclassical trajectory calculations and a rigorous statistical method
      based on the coupled-channel theory.

PMID- 16405359
TI  - The good news: it's our 60th birthday. The bad news: a giant, geriatric tsunami!

PMID- 16405360
TI  - Mental health promotion in older adults. Addressing treatment approaches and
      available screening tools.

PMID- 16405361
TI  - Osteoporosis in postmenopausal women. Therapy options across a wide range of risk
      for fracture.
AB  - Osteoporosis is a highly prevalent skeletal disorder characterized by compromised
      bone strength predisposing individuals to an increased risk of fractures.
      Fractures related to osteoporosis are frequently associated with chronic pain and
      decreased quality of life, as well as significant morbidity and mortality.
      Postmenopausal women are at higher risk for developing osteoporosis and
      osteoporosis-related fractures. Osteoporosis fractures are commonly asymptomatic,
      necessitating a need for proactive screening, diagnostic testing, and more
      importantly, therapeutic intervention that will rapidly reduce the risk of
      fractures in at-risk patients. Current pharmacologic prevention and treatment
      options for osteoporosis include antiresorptive therapies (alendronate,
      risedronate, ibandronate, raloxifene, hormone therapy, and calcitonin) and the
      anabolic agent teriparatide.

PMID- 16405362
TI  - Should bisphosphonates be continued indefinitely? An unusual fracture in a
      healthy woman on long-term alendronate.

PMID- 16405363
TI  - Solitary crystalline papule on right index finger. Patient reports history of
      distal osteoarthritis.

PMID- 16405364
TI  - Oral clefts with associated anomalies: methodological issues.
AB  - OBJECTIVE: To discuss methodological factors that account for the wide variation
      in the reported prevalence rates of anomalies associated with oral clefts.
      CONCLUSIONS: The published prevalences of associated anomalies vary considerably
      because of the following: (1) differences in case definition and
      inclusion/exclusion criteria; (2) length of time after birth that cases are
      examined; (3) variability of clinical expression of associated anomalies; (4)
      knowledge and technology available to produce syndrome delineation; (5) selection
      of patients, sources of ascertainment, and sample size; and (6) true population
      differences and changes in frequency over time.

PMID- 16405365
TI  - Levator veli palatini muscle fatigue during phonation in speakers with cleft
      palate with borderline velopharyngeal incompetence.
AB  - OBJECTIVE: This study examined whether the levator veli palatini muscle in
      speakers with borderline velopharyngeal incompetence (BVP) with surgically
      treated cleft palate might be more fatigable during speech than that in speakers
      without clefts. DESIGN: Each subject was asked to pronounce the syllable /pu/
      more than 50 times at a rate of one time per second. Mean power frequency (MPF)
      of one syllable was obtained from electromyogram data of the levator muscle by
      power spectral analysis. PARTICIPANTS: Five patients with postsurgical cleft
      palates, who were identified as having BVP by nasopharyngeal fiberscopy, served
      as subjects, and five participants without clefts served as the control group.
      RESULTS: In all participants without clefts, the slopes of the regression line
      relating MPF to the course of syllable repetition were negative but not
      significant. However, in all participants with BVP, the slopes of the regression
      line were significantly negative. CONCLUSIONS: These findings demonstrated that
      the levator muscle of speakers with BVP was more fatigable than that of speakers
      without clefts during repetition of syllables. This study suggests that the
      fatigability of levator muscle contributed to mild hypernasality in patients with
      BVP.

PMID- 16405366
TI  - Bleeding prophylaxis in a child with cleft palate and factor VII deficiency: a
      case report.
AB  - The association between factor VII deficiency and cleft palate has never been
      described. The case of a child with cleft palate and factor VII deficiency who
      successfully underwent palatoplasty is described in this article. To allow
      surgical treatment, through maintenance of a normal prothrombin time, the patient
      was given 15 microg/kg of recombinant factor VIIa every 12 hours, starting 20
      minutes before surgery and ending the third postoperative day. No abnormal
      perioperative bleeding was observed. Use of recombinant factor VIIa in bleeding
      prophylaxis or treatment is widespread. Doses are much higher in these cases. The
      reduction of dosage allows easier administration, especially in pediatric
      patients, without affecting drug efficacy.

PMID- 16405367
TI  - Both nasal cerebral heterotopia and encephalocele in the same patient.
AB  - OBJECTIVE AND PATIENT: Both nasal cerebral heterotopia and encephalocele are rare
      congenital benign masses of neurogenic origin caused by an embryonic
      developmental abnormality. It is generally accepted that nasal heterotopia is a
      sequelae to encephalocele. This report presents an unusual case of nasal cerebral
      heterotopia and encephalocele arising in the same patient. The patient had a
      firm, solid mass measuring 1.5 x 1.0 cm on the bridge of the nose covered with
      normal skin and another mass in the nasal cavity obstructing the right nasal
      cavity. Computed tomography (CT) demonstrated that the nasal bone separated these
      masses. CT also showed a bony defect at the skull base. Surgery consisted of
      dividing the encephalocele and closure of the skull base fistulae, along with
      nasal subcutaneous mass enucleation. RESULTS: Intraoperative examination
      indicated the existence of a pit on the nasal bone where the pedicle of the nasal
      subcutaneous mass connected. Microscopic examination of the nasal cavity mass
      demonstrated meningoencephalocele, and examination of the nasal subcutaneous mass
      demonstrated nasal cerebral heterotopia, which was confirmed by
      immunohistochemical staining. After 10 months, complete removal of the
      subcutaneous nasal mass was recognized and there was no evidence of recurrence.
      CONCLUSION: Findings in this case suggest that the nasal cerebral heterotopias
      will result from encephalocele.

PMID- 16405368
TI  - A pharyngeal and ectopic hypophysis in a neonate with craniofacial abnormalities:
      a case report and review of development and structure.
AB  - OBJECTIVE: A large excrescence was found bulging from the mucoperiosteum of the
      nasopharynx in a neonate displaying abnormal craniofacial features. The aim of
      this study was to determine the nature of this tissue mass. DESIGN: Histological
      examination of this mass of tissue and the surrounding nasopharyngeal mucosal
      tissue, as well as tissue located in the sella turcica of the sphenoid bone, were
      carried out. In addition, tissue in a canal connecting the large mass to the
      sella turcica was removed for analysis. RESULTS: Nervous elements and
      adenohypophyseal tissue were histologically identified in the large excrescence,
      but were separate from adenohypophyseal tissue of the pharyngeal hypophysis. Both
      structures were located in the mucoperiosteum of the nasopharynx. CONCLUSIONS:
      The large tissue mass found in the nasopharynx is histologically identical to a
      sellar hypophyseal gland, but differed from the adjacent pharyngeal hypophysis in
      histological composition. The mass, although sellar in nature, however, was
      placed ectopically in the nasopharynx and is hence termed pharyngosellar to
      indicate its abnormal position, as well as its origin.

PMID- 16405371
TI  - Use of vomer flap in palatoplasty: revisited.
AB  - OBJECTIVE: To present a new comprehensive and simple classification of vomerine
      flaps for palatoplasty. DESIGN: This classification has been developed on the
      basis of a literature search and our clinical experience. The vomerine flaps have
      been classified into three types, each with A and B subtypes. PATIENTS,
      PARTICIPANTS: Vomerine tissue has been used in more than 1000 palatoplasties over
      the past 17 years. The analysis includes 678 cleft palate patients for whom
      detailed records were available. Type II-A vomerine flaps were used most commonly
      in unilateral cleft palate patients, whereas Type II-B1 flaps were used in
      bilateral cleft palate patients. RESULTS: The overall fistula rate at the hard
      and soft palate junction was 2.95%. Although facial growth pattern was not
      recorded, obvious midface growth abnormalities were not observed in any of these
      patients. CONCLUSIONS: Vomerine tissue is available in the vicinity of the
      palatal defect. Raising of the vomerine flap is simple and safe. If properly
      designed, it can be used judiciously for closure of the nasal and oral defects in
      the cleft palate. We have used these flaps only to augment the nasal mucosal
      defect. This comprehensive classification will be useful in understanding,
      designing, and implementing these small, but very important, flaps.

PMID- 16405370
TI  - Contributions of PTCH gene variants to isolated cleft lip and palate.
AB  - OBJECTIVE: Mutations in patched (PTCH) cause the nevoid basal cell carcinoma
      syndrome (NBCCS), or Gorlin syndrome. Nevoid basal cell carcinoma syndrome may
      present with developmental anomalies, including rib and craniofacial
      abnormalities, and predisposes to several tumor types, including basal cell
      carcinoma and medulloblastoma. Cleft palate is found in 4% of individuals with
      nevoid basal cell carcinoma syndrome. Because there might be specific sequence
      alterations in PTCH that limit expression to orofacial clefting, a genetic study
      of PTCH was undertaken in cases with cleft lip and/or palate (CL/P) known not to
      have nevoid basal cell carcinoma syndrome. RESULTS: Seven new normal variants
      spread along the entire gene and three missense mutations were found among cases
      with cleft lip and/or palate. One of these variants (P295S) was not found in any
      of 1188 control samples. A second variant was found in a case and also in 1 of
      1119 controls. The third missense (S827G) was found in 5 of 1369 cases and in 5
      of 1104 controls and is likely a rare normal variant. Linkage and linkage
      desequilibrium also was assessed using normal variants in and adjacent to the
      PTCH gene in 220 families (1776 individuals), each with two or more individuals
      with isolated clefting. Although no statistically significant evidence of linkage
      (multipoint HLOD peak = 2.36) was uncovered, there was borderline evidence of
      significant transmission distortion for one haplotype of two single nucleotide
      polymorphisms located within the PTCH gene (p = .08). CONCLUSION: Missense
      mutations in PTCH may be rare causes of isolated cleft lip and/or palate. An as
      yet unidentified variant near PTCH may act as a modifier of cleft lip and/or
      palate.

PMID- 16405372
TI  - Comparison of resonance outcomes after pharyngeal flap and furlow double-opposing
      z-plasty for surgical management of velopharyngeal incompetence.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that no
      significant difference exists in the speech outcomes between patients with severe
      velopharyngeal incompetence (VPI) who receive a pharyngeal flap and patients with
      less severe VPI who receive a Z-plasty for management of VPI. DESIGN: This
      retrospective study from 1993 to 2002 included a review of pre- and postoperative
      perceptual speech and resonance assessments of patients with marginal VPI who
      received a Furlow double-opposing Z-plasty and patients with VPI who received a
      pharyngeal flap. SETTING: All patients had surgical management of VPI at the
      Cleft Palate-Craniofacial Clinic at University of Iowa Hospitals and Clinics.
      RESULTS: Both groups benefited from surgery with significant reduction in
      perceived hypernasality (p < .001). Comparison of postoperative assessments
      indicated no difference between the groups in hypernasality or hyponasality
      ratings. Neither group had a significant increase in hyponasality. CONCLUSION:
      Both pharyngeal flap and double-opposing Z-plasty proved equally effective at
      reducing hypernasality when the selection of the surgical procedures was based on
      preoperative ratings of perceived hypernasality and evaluation of velopharyngeal
      physiology. Severity of the VPI is an important factor when considering surgical
      management of VPI. Thorough preoperative evaluations of patients with VPI are
      essential in appropriate treatment planning.

PMID- 16405373
TI  - A therapeutic camp weekend for adolescents with craniofacial differences.
AB  - OBJECTIVE: A therapeutic camp weekend was developed for adolescents living with a
      facial difference. The camp comprised a program that involved personal challenges
      and group-building activities, as well as social recreational activities. This
      article outlines the camp intervention, with recommendations for future camp
      evaluation.

PMID- 16405374
TI  - Facilitating cleft palate team participation of culturally diverse families in
      South Africa.
AB  - OBJECTIVE: The Facial Cleft Deformities Clinic, University of Pretoria, Pretoria,
      South Africa, provides interdisciplinary team services to patients with cleft lip
      and palate and craniofacial anomalies. They represent the "rainbow nation" of
      South Africa and reflect the multicultural and multilingual nature of the
      population, which poses a challenge to effective and accountable service
      delivery. The aim of this study was to explore some cultural variations that
      exist in black families that influence their participation in the team approach
      and to describe the assets of families that may be used to empower them and to
      enhance service delivery. DESIGN: A descriptive survey research design. A
      questionnaire-by-interview procedure was utilized during routine visits of 35
      black families to the Facial Cleft Deformities Clinic. RESULTS: The results are
      discussed from an ethnographic perspective of the family and describe the
      knowledge base of the participants, the diagnosis and treatment of the children's
      cleft lip and palate, family structure and support systems, family income and
      education, and the geographical distribution of the participants. Implications
      for building family partnerships and for improving professionals' cultural
      competence in order to improve the quality of service delivery are presented.
      CONCLUSIONS: By viewing cultural differences on a continuum, following the asset
      based approach, applying knowledge based on contextually relevant research, and
      recognizing family uniqueness, families may be empowered to participate fully in
      the team approach to support their children with cleft lip and palate and
      craniofacial anomalies in attaining their full potential in the South African
      context.

PMID- 16405375
TI  - Feeding-facilitating techniques for the nursing infant with Robin sequence.
AB  - OBJECTIVE: To determine the effectiveness of feeding-facilitating techniques in
      children with Robin sequence. SETTING: Hospital de Reabilitacao de Anomalias
      Craniofaciais, University of Sao Paulo, Bauru, Sao Paulo, Brazil. PATIENTS:
      Twenty-six children less than 2 months of age with Robin sequence, whose only
      cause of respiratory obstruction was glossoptosis. Thirteen infants were treated
      by being placed in the prone position (Group 1), and 13 were treated by
      nasopharyngeal intubation (Group 2). INTERVENTIONS: During hospitalization, the
      following feeding-facilitating techniques were applied daily to all children:
      pacifier, massage to relax and anteriorize the tongue, long and soft bottle
      nipple with original or enlarged hole, global symmetric position, rhythmic
      movement of the nipple during suction, and insertion of the nipple on the tongue.
      RESULTS: During the first evaluation, Group 1 patients accepted 36.15 +/- 33.05
      mL milk orally within a period of 44.62 +/- 42.94 minutes, whereas Group 2
      ingested 20.00 +/- 20.51 mL milk within 30.38 +/- 25.77 minutes. A significant
      increase (p < .01) in the volume of ingested milk was observed for the two groups
      at hospital discharge after a mean treatment period of 10.7 days (Group 1: 63.46
      +/- 22.58 mL and Group 2: 55.00 +/- 13.07 mL). The mean duration of feeding
      decreased in the two groups, with a value of 21.54 +/- 7.18 minutes for Group 1
      and of 20.28 +/- 8.53 minutes for Group 2. CONCLUSION: The results showed that
      feeding-facilitating techniques can foster oral feeding in infants with Robin
      sequence.

PMID- 16405376
TI  - Antenatal transabdominal ultrasound detection of cleft lip and palate in Western
      Australia from 1996 to 2003.
AB  - OBJECTIVE: To determine the frequency of detection of cleft lip with or without
      cleft palate and isolated cleft palate from antenatal ultrasound examinations
      conducted on mothers of infants born with cleft lip and/or palate and isolated
      cleft palate in Western Australia from 1996 to 2003. DESIGN: Review of patient
      records and purpose-designed questionnaire sent to parents of children born with
      cleft lip and/or palate and isolated cleft palate. RESULTS: There were 308
      infants born with cleft lip and/or palate and isolated cleft palate in the study
      period. Of the 293 parents, 218 responses were available for the study (70.7%),
      and 2.9 +/- 1.8 SD antenatal ultrasound scans were performed on 216 women. No
      such scans were performed on two women. Cleft lip and/or palate was detected in
      22.2% of cases. There was no detection prior to 15 weeks gestational age in the
      137 women screened. Between 15 and 19 weeks gestational age, 174 scans detected
      30 cases. Between 20 and 29 weeks gestational age, 84 scans detected 11 cases.
      Between 30 and 40 weeks gestational age, 66 scans detected 7 cases. The detection
      rate for bilateral cleft lip and/or palate was 44.4% and for unilateral cleft lip
      and/or palate, 40.6%. Detection rate for isolated cleft lip was 33.3%. Antenatal
      ultrasound failed to detect any infants with an isolated cleft palate (n = 95).
      The rate of detection of cleft lip and/or palate increased through the study
      period. CONCLUSIONS: The rate of detection of cleft lip and/or palate in Western
      Australia is comparable to that for referral centers worldwide and is increasing.
      The rate of detection of the various types of cleft anomalies using antenatal
      ultrasound ranged from 0% to 44%.

PMID- 16405377
TI  - Five-year experience comparing resorbable to titanium miniplate osteosynthesis in
      cleft lip and palate orthognathic surgery.
AB  - OBJECTIVE: To evaluate 5-year outcome stability and complications in orthognathic
      surgery using resorbable versus titanium osteofixation. PATIENTS, METHODS: Twenty
      two cleft lip and palate maxillary retrognathia cases were operated on using
      either poly (70L-lactide-co-30DL-lactide) or titanium miniplate osteofixation.
      All had two-piece Le Fort I maxillary advancement osteotomy, 11 had simultaneous
      mandibular setback, and 13 had alveolar bone grafts. RESULTS: Average operative
      movement and postoperative instability recorded for maxillary horizontal movement
      (A-point-Nasion) were 2.5 mm and 2.1 mm for the study group, compared with 6.3 mm
      and 1.9 mm for the control group. For maxillary vertical movement (ANS-Nasion),
      measured values were 4.9 and 1.3 mm for the study group and 2.3 and 0.9 mm for
      the controls. For mandibular horizontal movement, measured values were 10.7 mm
      and 2.8 mm for the study group and 1.9 mm and 0.8 mm for the controls. Gonial
      angle measures were 7.1 degrees and 3.5 degrees for the study group and 6.7
      degrees and 3.1 degrees for the controls. Foreign body granuloma and fistulation
      occurred in 1 (9%) member of the study group, but was treated successfully with
      debridement; implant palpability subsided after 24 months. Three (27%) controls
      required plate removal, but the remaining plates were palpable. CONCLUSION: In
      the study group, horizontal maxillary stability appeared inferior to vertical
      stability, but mandibular stability was more reliable. Because groups were not
      matched for magnitude or direction of movement, the results of this study are
      preliminary and should be interpreted cautiously.

PMID- 16405378
TI  - The Pittsburgh Oral-Facial Cleft study: expanding the cleft phenotype. Background
      and justification.
AB  - The Pittsburgh Oral-Facial Cleft study was begun in 1993 with the primary goal of
      identifying genes involved in nonsyndromic orofacial clefts in a variety of
      populations worldwide. Based on the results from a number of pilot studies and
      preliminary genetic analyses, a new research focus was added to the Pittsburgh
      Oral-Facial Cleft study in 1999: to elucidate the role that associated phenotypic
      features play in the familial transmission patterns of orofacial clefts in order
      to expand the definition of the nonsyndromic cleft phenotype. The purpose of this
      paper is to provide a comprehensive review of phenotypic features associated with
      nonsyndromic orofacial clefts. These features include fluctuating and directional
      asymmetry, non-right-handedness, dermatoglyphic patterns, craniofacial
      morphology, orbicularis oris muscle defects, dental anomalies, structural brain
      and vertebral anomalies, minor physical anomalies, and velopharyngeal
      incompetence.

PMID- 16405379
TI  - Changes in nasorespiratory function in association with maxillary distraction
      osteogenesis in subjects with cleft lip and palate.
AB  - OBJECTIVE: The current study aimed to determine how nasorespiratory function
      changes in association with maxillary distraction osteogenesis (DO). Furthermore,
      with regard to impaired nasorespiratory function, the possibility of a
      relationship between the cleft side and laterality and any effect of maxillary
      distraction osteogenesis was investigated. DESIGN: In this descriptive,
      prospective clinical report, subjective and objective data regarding
      nasorespiratory function before and after maxillary distraction osteogenesis were
      compared. SUBJECTS: Data from 13 subjects with cleft lip and palate were used.
      Subjects had a severe maxillary deficiency and underwent distraction osteogenesis
      using a rigid external device system. OUTCOME MEASURES: The subjective measure
      was the score on a questionnaire regarding nasorespiratory function using a
      visual analog scale. The objective measure was nasal resistance. RESULTS: The
      visual analog scale score for two items significantly decreased just after
      distraction osteogenesis. Nasal resistance also significantly decreased 1 year
      after distraction osteogenesis. Moreover, nasal resistance on the cleft side was
      significantly greater than that on the noncleft side just before and 1 year after
      distraction osteogenesis. There was a significant positive correlation between
      changes in the visual analog scale score and nasal resistance. CONCLUSIONS: These
      results suggest that nasorespiratory function changes in association with
      maxillary distraction osteogenesis in subjects with cleft lip and palate.
      Moreover, it appears that nasal obstruction on the cleft side does not change in
      subjects with unilateral cleft lip and palate.

PMID- 16405380
TI  - The dynamics in implantation for patients with clefts.
AB  - OBJECTIVE: To investigate the stresses and strains of an endosseous dental
      implant in patients with different types of cleft palate in a finite element
      model. MATERIALS AND METHODS: Seven three-dimensional (3D) maxillary models were
      designed on a personal computer according to computed tomography slice data
      obtained from seven dry skulls. Next, computer-aided modification was performed
      on each model to produce three other 3D models with different cleft patterns.
      Thus, four model types with different cleft patterns were designed and termed
      NORM (without cleft), ALVEOLAR (only alveolar cleft), PALATAL (only palatal
      cleft), and COMPLETE (complete cleft). An implant was embedded into the molar
      region of each model, and a 300-N vertical load and 50-N horizontal load were
      applied to simulate mastication. Under these conditions, the stresses occurring
      at the implant-bone interface were calculated by finite element analysis.
      RESULTS: Different stress patterns were observed between the models with a
      palatal cleft (PALATAL and COMPLETE) and those without palatal cleft (NORM and
      ALVEOLAR). Regarding vertical load application, greater stresses occurred in
      PALATAL and COMPLETE types than in NORM and ALVEOLAR types. On application of a
      horizontal load, though the stresses did not show quantitative difference, their
      vector patterns differed. CONCLUSION: In patients with palatal clefts,
      characteristic stress patterns occur on the bone-implant interface during
      mastication. This should be taken into consideration when performing an implant
      treatment in patients with clefts.

PMID- 16405381
TI  - Management of the prominent premaxilla in bilateral cleft lip and palate.
AB  - DESIGN AND OBJECTIVE: This study was designed to present our philosophy in
      managing the prominent premaxilla in patients with bilateral cleft lip and
      palate. Indications, contraindications, and the pre- and postoperative
      orthodontic role are defined. SETTING: Tertiary care, cleft palate and
      craniofacial center-academic institution. PATIENTS: Under review were four cases
      of bilateral cleft lip and palate presenting with prominent premaxilla and
      operated on by a single surgeon between 1996 and 2004. CONCLUSION: With
      appropriate patient selection, bilateral alveolar bone grafting with premaxillary
      repositioning is a safe procedure and can produce good aesthetic and functional
      results.

PMID- 16405382
TI  - Assessment of dental arch relationships in Japanese patients with unilateral
      cleft lip and palate.
AB  - OBJECTIVE: Evaluation of the dental arch relationships of Japanese patients with
      unilateral cleft lip and palate (UCLP) from the orthodontic clinic of the
      University of Tokyo Hospital (UTH) compared with patients treated by the Oslo
      Cleft Team, Norway. DESIGN: Retrospective study and comparison with previous
      reports. MATERIALS: Dental models of 24 patients with UCLP in UTH taken before
      orthodontic treatment and before alveolar bone grafting were included. Surgeons
      in many hospitals performed primary surgeries. These models were matched for age
      and gender with 24 models from a consecutive series of patients treated by the
      Oslo Cleft Team as part of the Eurocran Good Practice Archive. A total of 48
      models were evaluated. MAIN OUTCOME MEASURE: Dental arch relationship was rated
      with the Goslon Yardstick. The strength of agreement of rating was assessed with
      weighted kappa statistics. RESULTS: Intra- and interexaminer agreements evaluated
      by weighted kappa statistics were high, indicating good reproducibility. Almost
      60% of the patients in UTH were classified into poor or very poor categories, and
      the mean Goslon score was 3.50. These results show a contrast to those in Oslo
      and were the poorest in comparison with previous reports. CONCLUSION: Dental arch
      relationships in patients with UCLP in UTH were poor. This seemed to be
      attributable to surgical procedures, but a factor of racial difference in the
      craniofacial morphology was also considered. Further intercenter research is
      required to clarify this point.

PMID- 16405383
TI  - Social role valorization insights into the social integration conundrum.
AB  - More and more persons with mental retardation and psychiatric disabilities are
      present in mainstream society, yet have little interaction and few relationships
      outside their own peer groups of devalued persons. Social integration remains a
      desirable yet elusive goal for most human service organizations, and there
      continues to be a certain amount of confusion about what constitutes social
      integration. Recent reviews in North America and Europe testify to the difficulty
      of achieving social integration, particularly for people with mental retardation
      and psychiatric disabilities. Social role valorization, with its use of the
      social role concept, provides useful insights and tools for analyzing the social
      integration conundrum. A social role conceptualization of social integration is
      proposed and an illustrative example is provided.

PMID- 16405384
TI  - Sleep and developmental disabilities: assessment, treatment, and outcome
      measures.
AB  - People with developmental disabilities sleep less and experience higher incidence
      of clinical sleep disorders than the general population. Exploring the
      neurophysiology linking sleep with daytime performance in patients with
      developmental disabilities is now possible using minimally sufficient sleep and
      sleep-sensitive behavioral assays. Although frequent sampling represents the
      primary difficulty, it is required to untangle coincident effects of sleep
      quality amidst circadian variation. Recent evidence finds high quality sleep
      promotes brain plasticity, improves health measures, and enriches quality of
      life. Sleep treatments for apnea, insomnia, restless limbs, and conditioned sleep
      aversion are available, although not readily provided, for people with
      developmental disabilities. This population would gain both clinical and
      behavioral benefits as improved sleep-monitoring, behavioral testing, and sleep
      treatment technology is adapted to their needs.

PMID- 16405385
TI  - Mental disabilities in Western civilization from Ancient Rome to the Prerogativa
      Regis.
AB  - A preliminary survey of formal concepts of disability from the Twelve Tables of
      Rome of the 5th century BCE to the Prerogativa Regis in English law of the late
      13th century CE is presented. Firm conclusions are restricted by problems in
      translation and other limitations in available data. However, it appears that the
      concept of intellectual disability and its distinction from episodic mental
      illness first emerged in several subcultures of Western civilization during the
      height of ancient imperial Rome and during the early medieval period in Northern
      European and Arabic civilization.

PMID- 16405386
TI  - Medicaid managed care model of primary care and health care management for
      individuals with developmental disabilities.
AB  - Lack of sufficient accessible community-based health care services for
      individuals with developmental disabilities has led to disparities in health
      outcomes and an overreliance on expensive models of care delivered in hospitals
      and other safety net or state-subsidized providers. A functioning community-based
      primary health care model, with an integrated care management component,
      functioning in the general health care practice marketplace, is described and
      shown to address recent Surgeon General recommendations as well as evaluative
      criteria for availability, affordability, acceptability, and appropriateness of
      care. The model functions in both fee-for-service and managed care environments,
      including Medicaid managed care for individuals with developmental disabilities.
      Experience shows this model to be both scalable and replicable, resulting in
      positive health outcomes and increased patient satisfaction.

PMID- 16405387
TI  - Promoting friendship through best buddies: a national survey of college program
      participants.
AB  - Best Buddies is a nonprofit organization whose mission is to enhance the lives of
      people with intellectual disabilities through one-to-one friendships with
      individuals without disabilities. A cross-sectional survey was conducted with
      Best Buddies College Program participants located within the United States.
      Survey findings suggest that college students and people with intellectual
      disabilities benefited from participation in Best Buddies. The vast majority of
      college students and people with intellectual disabilities reported enjoying
      their experience and engaging in friendship activities that were mutually
      beneficial to those involved. Most people with intellectual disabilities also
      indicated their lives had been enhanced as a result of Best Buddies, although the
      percentage was lower than that of college students.

PMID- 16405388
TI  - Presidential address 2005: peace-making is the answer: spiritual valorization and
      the future of our field.

PMID- 16405389
TI  - Against psychotherapy with people who have mental retardation: in response to the
      responses.

PMID- 16405390
TI  - Power of a poet: Karl Williams.

PMID- 16405391
TI  - Growth of U.S. public spending for intellectual/developmental disabilities slowed
      down 2002-2004.

PMID- 16405395
TI  - An amelogenin minigene to study alternative splicing.
AB  - Diversity in gene expression is commonly observed as a result of alternative
      splicing of RNA transcripts. This is true in the case of amelogenin, one of the
      enamel matrix proteins. Our hypothesis is that additional amelogenin mRNA
      transcripts are generated in vivo, but these transcripts have yet to be observed
      because of the limitations of currently used detection methodologies. For this
      study our objective was to create an amelogenin minigene to study amelogenin RNA
      splicing events in cell lines of diverse character. Mouse genomic DNA was used as
      a PCR template to amplify the amelogenin DNA sequence spanning exons 2-7. The
      resulting PCR-generated DNA was subcloned in an expression vector. This resulting
      amelogenin minigene was shown to be functionally active by transfection into
      multiple cell lines. We have successfully cloned an amelogenin minigene, and as a
      result we describe and discuss novel amelogenin alternatively spliced
      transcripts.

PMID- 16405396
TI  - Enhancer- and silencer-like sequences that mediate insulin-like growth factor
      binding protein-2 gene expression in uterine cells of pregnancy.
AB  - The regulation of insulin-like growth factor-binding protein-2 (IGFBP-2) gene
      transcription in specific cell and developmental contexts is not well understood.
      Here, we identified DNA regions that mediate IGFBP-2 gene transcription in two of
      the three major cell types of the uterine endometrium of the early pregnant pig.
      Two clusters of transcriptional start sites at nucleotides -109/-105 and -96/-87
      (+1, translational initiation site) in the porcine IGFBP-2 gene were localized in
      uterine endometrium and in primary cultures of endometrial glandular epithelial
      (GE) and stromal (ST) fibroblastic cells. Upstream regions of this gene (spanning
      -1,397/+73) were fused to a luciferase reporter gene, and the constructs were
      transiently transfected into endometrial GE and ST cells representative of
      pregnancy days 12 and 18 (day 115 = parturition). A short (110 bp) upstream
      region (-874/-765) stimulated the IGFBP-2 and heterologous SV40 promoters in the
      two cell types at both pregnancy days. Two noncontiguous copies of the novel
      sequence motif TCAGGG within the 110-bp fragment were implicated in
      transcriptional activity, since block mutation of these sequences led to a
      repression of SV40 basal promoter activity in endometrial cells. Southwestern
      blotting identified an endometrial nuclear protein of 34-kDa molecular weight
      that bound an oligonucleotide containing this motif, and EMSA suggested robust
      expression of this protein in early pregnancy endometrium and in ovary but at
      much reduced levels in endometrium at later pregnancy. A pair of E-box elements
      (CANNTG) within the 110 bp region was stimulatory to IGFBP-2 promoter activity;
      block mutation of these converted the 110-bp region into a potent transcriptional
      silencer in all but day 18 ST cells. Results identify novel DNA motifs that
      regulate the IGFBP-2 gene promoter in uterine endometrium in pregnancy-associated
      fashion.

PMID- 16405397
TI  - The human pre-B cell line Nalm-6 is highly proficient in gene targeting by
      homologous recombination.
AB  - Gene targeting provides a powerful means for analyzing gene function, as
      exemplified by knockout mouse studies and recent work with the highly
      recombinogenic chicken DT40 B-lymphocyte line. In human cultured cells, however,
      the low frequency of gene targeting is a serious barrier to efficiently generate
      knockout clones. Moreover, commonly used human cell lines are karyotypically
      abnormal or unstable. Here, we show using promoterless targeting constructs that
      Nalm-6, a human pre-B ALL cell line, is highly proficient for gene targeting by
      homologous recombination. Indeed, the efficiency of TP53 gene targeting in Nalm-6
      appears nearly two orders of magnitude higher than that in HCT116, a colon cancer
      cell line popularly used for gene targeting. Expression analysis revealed a lack
      of MSH2 expression in this cell line. As Nalm-6 has a stable neardiploid
      karyotype with normal p53 status, our results underscore the usefulness of Nalm-6
      for gene knockout studies in humans.

PMID- 16405398
TI  - Improved humoral immunity against tuberculosis ESAT-6 antigen by chimeric DNA
      prime and protein boost strategy.
AB  - Ag85A and ESAT-6 proteins of Mycobacterium tuberculosis (M.TB) are important
      protective antigens. The 32-kDa Ag85A is a strong immunogen in both small and
      large animals. However, the 6-kDa ESAT-6 has relatively low inherent
      immunogenicity, especially in large animals. To improve the immunogenicity of
      ESAT-6 in animals, we made chimeric DNA vaccines, HG856K and HG856A, by inserting
      the esat-6 gene into the Kpn I or Acc I endonuclease restriction site of the
      ag85a gene, respectively. BALB/c mice were injected intramuscularly three times
      with the 10-microg singular DNA vaccine (HG85 encoding for Ag85A or HG6 encoding
      for ESAT-6) or chimeric DNA vaccine (HG856K or HG856A) followed by
      electroporation (EP). Ten days after the last DNA vaccination, mice received a
      booster immunization intraperitoneally with 50-microg pure recombinant protein
      Ag85A or ESAT-6 without adjuvant. Additional groups of mice immunized with
      chimeric DNA vaccines were boosted with two mixed proteins (Ag85A/ESAT-6) at the
      same time. The results showed that the immunogenicity of M.TB ESAT-6 antigen was
      not improved by priming with the HG6 DNA vaccine. However, the humoral immunity
      against the ESAT-6 antigen was significantly increased in the mice primed with
      chimeric DNA vaccines, HG856K or HG856A, followed by boosting with ESAT-6 or ESAT
      6/Ag85A mixed proteins.

PMID- 16405399
TI  - Transcriptional status of known and novel genes tagged with consensus of 33.15
      repeat loci employing minisatellite-associated sequence amplification (MASA) and
      real-time PCR in water buffalo, Bubalus bubalis.
AB  - We conducted minisatellite-associated sequence amplification (MASA) with an oligo
      (5' CACCTCTCCACCTGCC 3') based on consensus of 33.15 repeat loci using cDNA from
      the testis, ovary, spleen, kidney, heart, liver, and lung of water buffalo
      Bubalus bubalis and uncovered 25 amplicons of six different sizes (1,263,
      846/847, 602, 576, 487, and 324 base pairs). These fragments, cloned and
      sequenced, were found to represent several functional, regulatory, and structural
      genes. Blast search of all the 25 amplicons showed homologies with 43
      transcribing genes across the species. Of these, the 846/847-bp fragment, having
      homology with the adenylate kinase gene, showed nucleotide changes at six
      identical places in the ovary and testis. The 1,263; 324; and 487-bp fragments
      showed homology with the secreted modular calcium binding protein (SMOC-1),
      leucine-rich repeat neuronal 6A (LRRN6A) mRNA, and human TTTY5 mRNA,
      respectively. Real-time PCR showed maximum expression of AKL, LRRN6A, and T-cell
      receptor gamma (TCR-gamma)-like genes in the testis, SMOC-1 in the liver, and the
      T-cell receptor-like (TCRL) gene in the spleen compared to those used as
      endogenous control. We construe that these genes have evolved from a common
      progenitor and conformed to various biological functions during the course of
      evolution. MASA approach coupled with real-time PCR has potentials to uncover
      accurate expression of a large number of genes within and across the species
      circumventing the screening of cDNA library.

PMID- 16405400
TI  - Microarray analysis of butyrate regulated genes in colonic epithelial cells.
AB  - Butyrate is a naturally occurring product of colonic microbial fermentation of
      dietary carbohydrates that escape hydrolysis in the small intestine. Butyrate
      plays a significant role in the maintenance of colonic tissue homeostasis by
      regulating the expression of genes associated with the processes of
      proliferation, differentiation, and apoptosis. Using microarray analysis, we
      assessed changes in the expression of 19,400 genes in response to butyrate in a
      human colonic epithelial cell line. Among these, we have identified 221
      potentially butyrate- responsive genes specifically associated with the processes
      of proliferation, differentiation, and apoptosis. Of these genes, 59 are
      upregulated and 162 downregulated, in accordance with the known modes of action
      of butyrate. The changes in the expression levels (up- or downregulation) of many
      of these genes were found to be opposite to that reported in colon cancer tissue,
      where the intracellular concentration of butyrate would be reduced due to the
      decline in expression of the colonic butyrate transporter, MCT1.

PMID- 16405401
TI  - DNA interaction with human serum albumin studied by affinity capillary
      electrophoresis and FTIR spectroscopy.
AB  - The question addressed in this study is how does the protein-DNA complexation
      affect the structure and dynamics of DNA and protein in aqueous solution. We
      examined the interaction of calf-thymus DNA with human serum albumin (HSA) in
      aqueous solution at physiological conditions, using constant DNA concentration of
      12.5 mM (phosphate) and various HSA contents 0.25 to 2% or 0.04 to 0.3 mM.
      Affinity capillary electrophoresis and FTIR spectroscopic methods were used to
      determine the protein binding mode, the association constant, sequence
      preference, and the biopolymer secondary structural changes in the HSA-DNA
      complexes. Spectroscopic evidence showed two types of HSA-DNA complexes with
      strong binding of K(1) = 4.5 x 10(5) M(-1) and weak binding of K(2) = 6.10 x
      10(4) M(-1). The two major binding sites were located on the G-C bases and the
      backbone PO(2) group. The protein-DNA interaction stabilizes the HSA secondary
      structure. A minor alteration of B-DNA structure was observed, while no major
      protein conformational changes occurred.

PMID- 16405402
TI  - When the facts change, I change my mind--do you?

PMID- 16405403
TI  - Radioiodine therapy for thyroid cancer and hyperthyroidism in patients with end
      stage renal disease on hemodialysis.
AB  - Treatment with radioactive iodine ((131)I) may be necessary for thyroid cancer or
      for hyperthyroidism in patients with end-stage renal disease who require
      hemodialysis. Because (131)I is cleared mainly by the kidneys in patients with
      normal renal function, many issues arise in patients who require (131)I treatment
      but who are on hemodialysis. This paper presents a case report of a patient on
      dialysis who required treatment with (131)I for thyroid cancer. We describe a
      mathematical model, which suggests that the treatment dose of (131)I for a
      patient with thyroid cancer on hemodialysis would be approximately 13%-28% of a
      typical empiric dose of (131)I for a patient with normal renal function. Also, we
      present a comprehensive review and discussion of the literature on patients who
      are receiving hemodialysis who were treated with (131)I for either thyroid cancer
      or hyperthyroidism. Using a multidisciplinary approach and special precautions,
      (131)I therapy can be administered safely and effectively for patients with
      thyroid cancer or hyperthyroidism who are receiving hemodialysis.

PMID- 16405404
TI  - A case of hypersensitivity syndrome induced by methimazole for Graves' disease.
AB  - Drug-induced hypersensitivity syndrome is one of the most severe forms of drug
      eruption and is characterized by high fever and multiorgan involvement.
      Reactivation of human herpesvirus-6 (HHV-6) or cytomegalovirus (CMV) has been
      suggested to be involved in this syndrome, although the exact role of these
      viruses remains elusive. We report the case of a 50-year-old Japanese male with
      Graves' disease who developed hypersensitivity syndrome caused by the antithyroid
      drug methimazole (MMI). After treatment with MMI 30 mg three times daily for
      1(1/2) months, the patient developed generalized exfoliative erythematous
      eruption and high fever. Cessation of treatment with the drug improved his
      condition. Readministration of MMI worsened his clinical features. Treatment with
      high-dose methylprednisolone for 6 days and subsequent administration of
      prednisolone 20 mg twice daily improved his clinical manifestations. Elevated
      titers of anti-HHV-6 immunoglobulin G (IgG) and anti-CMV IgG antibodies were
      observed, and these gradually decreased during the clinical course, indicating
      reactivation of HHV-6 and CMV. Drug-induced lymphocyte stimulation test for MMI
      was negative. This is the first reported case of MMI-induced hypersensitivity
      syndrome associated with the reactivation of HHV-6 and CMV.

PMID- 16405405
TI  - Amiodarone-induced hyperthyroidism in a patient with functioning papillary
      carcinoma of the thyroid and extensive hepatic metastases.
AB  - Thyroid hormone producing thyroid carcinoma is an uncommon cause of
      thyrotoxicosis. A patient with extensive hepatic metastases from well
      differentiated carcinoma is presented. Administration of amiodarone for atrial
      fibrillation led to the development of hyperthyroidism. Precipitation of
      thyrotoxicosis by iodine-containing compounds in patients with thyroid carcinoma
      is rare. The relatively high iodine load and the slow elimination of amiodarone
      complicate the clinical management of such patients.

PMID- 16405406
TI  - Intrauterine diagnosis and management of fetal goitrous hypothyroidism: a report
      of an Iranian family with three consecutive pregnancies complicated by fetal
      goiter.
AB  - The diagnosis and treatment of hypothyroidism during the fetal period may
      decrease perinatal morbidity and are believed to be important to optimize growth
      and intellectual development. Herewith a case report of fetal goitrous
      hypothyroidism is presented in a euthyroid mother, detected at 34 weeks'
      gestation by ultrasonography, and treated with intra-amniotic levothyroxine
      injections. The mother had two previous consecutive pregnancies (13 and 8 years
      ago), also complicated by the occurrence of fetal goiter, resulting in tracheal
      compression, asphyxia, and early neonatal death in the first and in an emergency
      cesarean section delivery, because of fetal malpresentation, in the second
      neonate affected by congenital hypothyroidism (CH). The present male newborn,
      although born without observable goiter, had a large thyroid on ultrasonography
      and an early rise of his peripheral venous blood thyrotropin confirmed the
      diagnosis of CH. Low serum thyroglobulin in the proband and his older brother and
      parental consanguinity was mostly compatible with a thyroglobulin defective
      synthesis and secretion as the cause of CH and fetal goiter. Despite apparently
      sufficient dose of intraamniotic levothyroxine injections repeated weekly from 34
      37 weeks' gestation (i.e., four injections of 500 microg levothyroxine), neonatal
      bone age on the second day of life showed delayed skeletal maturation.

PMID- 16405407
TI  - A Greek family with a follicular variant of familial papillary thyroid carcinoma:
      TCO, MNG1, fPTC/PRN, and NMTC1 excluded as susceptibility loci.
AB  - The familial form of nonmedullary thyroid carcinoma (FNMTC) has been recognized
      as a distinct clinical entity and is characterized by multifocality and a more
      severe phenotype than its sporadic counterpart. The majority of FNMTC pedigrees
      are small in size, show variable modes of inheritance, and may present with a
      variety of additional benign thyroid disorders. The existence of marked
      phenotypic differences between FNMTC families suggests that there is genetic
      heterogeneity. Recent studies have mapped a susceptibility locus for FNMTC at
      2q21. This locus appears particular relevant to families with at least one case
      of the follicular variant of papillary thyroid cancer (fvPTC). We describe the
      clinical and pathologic characteristics of a large three-generation fPTC kindred,
      with two of the four PTC patients presented with the follicular variant of PTC.
      It is of interest the occurrence of PTC in three siblings within a period of 3
      years. In addition, multinodular goiter (MNG) was diagnosed in seven individuals,
      lymphocytic thyroiditis in four, while one diagnosed with a benign adenoma. From
      the PTC patients, one had MNG and fvPTC, one MNG, lymphocytic thyroiditis and
      papillary pattern of PTC, one lymphocytic thyroiditis and fvPTC, and one MNG and
      papillary pattern of PTC. The inheritance pattern was autosomal dominant with
      incomplete penetrance and women were affected more frequently than men.
      Considering all PTC-affected individuals, the limit of detection (LOD) score we
      got for this family on 2q21 was 0.5. The low LOD score is caused by a PTC patient
      who does not share the affected haplotype, suggesting that maybe a new locus for
      PTC predisposition is present in this kindred. Linkage analysis also excluded
      TCO, MNG, and fPTC/PRN as susceptibility loci to FNMTC in this family.

PMID- 16405409
TI  - Paraganglioma-like medullary thyroid carcinoma: a rare entity.
AB  - OBJECTIVE: The wide variety of rare histologic variants of medullary thyroid
      carcinoma (MTC) may make the differential diagnosis difficult. Pathologic
      examination of the resected specimen will not always be able to confirm the
      diagnosis, leaving the surgeon with an uncertainty as to what type of resection
      is best for the patient. The following report describes the case of a 58-year-old
      man with the rare diagnosis of paraganglioma-like MTC. METHODS: The patient
      presented with markedly elevated calcitonin (CT) and carcinoembryonic antigen
      (CEA) levels. A 1-cm tumor was detected in the right lobe of the thyroid. Based
      on the clinical diagnosis of MTC, we performed a total thyroidectomy with
      lymphadenectomy of the central and right lateral compartments. Paraffin sections
      of the resected specimen were stained with hematoxylin and eosin (H&E) and
      immunohistochemically characterized using antibodies to CT, CEA, chromogranin A,
      thyroglobulin, synaptophysin, sustentacular cells (SCs), low- and high-molecular
      cytokeratins (CK 5/6, 7, 18, 20), epidermal growth factor-receptor (EGFR),
      thyroid transcription factor-1 (TTF-1), bcl-2, Melan A, C-kit, neuron-specific
      enolase (NSE), and galectin-3. The patient's blood and tumor tissue were examined
      for mutations in the RET-protooncogene. RESULTS: H&E staining of both frozen and
      permanent sections was unable to differentiate benign from malignant tissue.
      Typical morphologic characteristics for MTC were completely absent. Only the
      additional finding of positivity for synaptophysin and numerous SC cells visible
      in-between neoplastic cells made the diagnosis of paraganglioma-like MTC
      possible. Sequencing of the RET proto-oncogene revealed no mutations.
      CONCLUSIONS: There are subgroups of MTC that present clinically similar to
      classic MTC, but in which missing typical morphologic characteristics make
      histopathology diagnosis difficult. In these cases, diagnosis, operative
      decisions, and follow-up strategies should be based on preoperative biochemical
      markers, imaging findings, and clinical parameters in accordance to the
      guidelines for classic MTC.

PMID- 16405408
TI  - RET/PTC3 rearrangement and thyroid differentiation gene analysis in a struma
      ovarii fortuitously revealed by elevated serum thyroglobulin concentration.
AB  - Struma ovarii (SO) is usually asymptomatic and only in a few cases it is
      associated with thyrotoxicosis. The presurgical diagnosis is very uncommon. In
      the majority of cases a pelvic mass is discovered at physical examination or by
      abdominal ultrasound. Only the hystopathologic examination is able to reveal the
      characteristic features of SO, with thyroid cells organized in follicles as the
      main tumoral tissue constituent. The histologic recognition of malignancy is not
      easy and usually requires an exhaustive sampling of the lesion to evaluate the
      extracapsular invasion. We report the case of a 59-year-old woman who came to our
      observation for the fortuitous finding of elevated serum thyroglobulin (Tg)
      levels (600-800 ng/mL). Because the thyroid function was normal and the
      ultrasound showed only a subcentrimetric nodule, the clinical suspicious of a SO
      was considered. Ultrasound examination of the abdomen showed a solid mass of 2 cm
      in the left ovary. A (131)I uptake was observed at scintiscan in the site of the
      solid mass. Three months after the resection of the left ovary serum Tg levels
      were markedly reduced (106 ng/mL), and its values continued to decrease down to
      34 ng/mL at last control. The histology showed that the ovarian mass was mainly
      constituted of thyroid tissue (98%), with no malignant features. The molecular
      analysis of several thyroid differentiation gene mRNAs in the SO tissue showed an
      abundant expression of all genes but pendrin (PDS). A reduced PDS mRNA expression
      might explain the defective thyroxine (T(4)) production. Despite the absence of
      malignant features, the expression of RET/PTC3 rearrangement was found, raising
      the possibility of a potential malignant nature of the tumor. A cancer-free
      period of 3-4 years, as in our patient, is not long enough to definitively
      exclude a late onset metastatic disease but, unfortunately, the patient died of
      nonmedical reasons. In conclusion, we report a case of SO that, to our knowledge,
      is the first in which the clinical suspicion arose from the inappropriately
      elevated presurgical serum levels of Tg. A quite exhaustive molecular analysis of
      thyroid specific genes and oncogenes provided two interesting findings: the low
      PDS mRNA expression, which may explain the low hormonal production and the
      absence of thyrotoxicosis and the presence of a RET/PTC3 rearrangement, which
      prompts the possibility of a late malignant evolution.

PMID- 16405410
TI  - Consumptive hypothyroidism caused by paraneoplastic production of type 3
      iodothyronine deiodinase.
AB  - Consumptive hypothyroidism is characterized by excessive inactivation of thyroid
      hormone by type 3 iodothyronine deiodinase (D3). Previously this rare syndrome
      was described in association with massive hemangiomas in children and in a single
      case of a hemangioendothelioma in an adult. Here we report the first case of
      consumptive hypothyroidism from a nonvascular tumor in a patient who required
      supraphysiologic doses of levothyroxine prior to the resection of a large
      malignant solitary fibrous tumor. The tumor expressed D3 message, protein and
      exhibited functional D3 enzymatic activity. The clinical presentation of this
      patient expands the differential diagnosis of hypothyroidism, adds to the growing
      list of paraneoplastic syndromes that impact the endocrine system, and extends
      the spectrum of tumor types associated with consumptive hypothyroidism.

PMID- 16405411
TI  - Successful use of iodine and levothyroxine to treat Graves' disease in a pregnant
      patient with allergy to antithyroid drugs and high thyrotropin-binding inhibitor
      immunoglobulin after radioiodine therapy.
AB  - High titer of thyrotropin-binding inhibitor immunoglobulin (TBII) in patients
      with Graves' disease can cause fetal hyperthyroidism during pregnancy. Prevention
      of fetal hyperthyroidism by administration of antithyroid drug (ATD) and
      levothyroxine (LT(4)) to pregnant patients who previously received ablative
      therapy has been reported. We administered iodine and LT(4) to a patient during
      gestation, because she had a severe adverse reaction to ATD. Although gestation
      proceeded normally, the infant showed transient neonatal hyperthyroidism right
      after birth. We believe that the fetus would have developed hyperthyroidism if we
      had not administered iodine to the mother. Administration of iodine and LT(4) to
      a pregnant patient with Graves' disease showing a high TBII after ablative
      therapy should be considered in rare patients with allergy to ATD.

PMID- 16405412
TI  - An authentic malignant epithelioid hemangioendothelioma of the thyroid: a case
      report and review of the literature.
AB  - Hemangioendotheliomas of the thyroid are neoplasms that are rarely encountered in
      the Alpine region in Europe. The endemic goiter in this iodine-deficient region
      can be considered as a predisposing factor. We report the second case of an
      epithelioid hemangioendothelioma (EHE) of the thyroid gland and the first
      clinical case with malignant behavior. A 73-year-old woman with a long history of
      multinodular goiter presented with a rapidly growing thyroid mass, free of
      distant metastases. A total thyroidectomy was performed. Histologically the
      lesion had characteristic epithelioid and spindle cell proliferation in a
      background of chondromyxoid stroma. Cytoplasmic vacuolization in the epithelioid
      and spindle cells were present. Tumor cells were positive for factor VIII-related
      antigen, MNF116, PAN-ceratin, CD 34, and CD 31 and negative for cytokeratin
      allowing the diagnosis of EHE. Nine months after the primary resection the tumor
      locally recurred. A palliative resection was performed in a second operation
      followed by interferon-alpha therapy. The patient rapidly developed a second
      local relapse and died 13 months after the diagnosis of an EHE had been made. An
      improvement of the very poor prognosis of this rare tumor may depend on early
      tumor diagnosis and surgery combined with a multimodal treatment.

PMID- 16405413
TI  - A case of aggressive carcinoma showing thymus-like differentiation with distant
      metastases.

PMID- 16405415
TI  - Acute thyroiditis of actinomycosis.

PMID- 16405414
TI  - Development of severe thyroid-associated ophthalmopathy in a patient with
      disseminated thyroid cancer treated with recombinant human
      thyrotropin/radioiodine and retinoic acid.
AB  - We present a case in which a patient with disseminated well-differentiated
      papillary thyroid cancer developed severe thyroid-associated ophthalmopathy.
      Eight years after initial surgery and ablative radioiodine therapy the patient
      was found to have multiple pulmonary metastases. The metastases showed poor
      uptake of radioiodine. An attempt was made to use 13-cis-retinoic acid in order
      to achieve a redifferentiation of the thyroid cancer cells before recombinant
      human thyrotropin (rhTSH) stimulated radioiodine therapy. The treatment did not
      improve the uptake of radioiodine. However, approximately 2 weeks after
      completion of the treatment the patient experienced discomfort in her eyes and
      then over the next months she developed a severe ophthalmopathy. The analyses of
      TSH receptor antibodies and S-thyroglobulin simultaneously showed a pronounced
      increase. An association between therapy given and severe ophthalmopathy cannot
      be excluded.

PMID- 16405416
TI  - Slow radioactive saliva transit through the esophagus mimicking a mediastinal
      thyroid mass in a patient with myasthenia gravis.

PMID- 16405417
TI  - A rapidly enlarging thyroid mass as the initial presentation of metastatic
      hepatocellular carcinoma.

PMID- 16405418
TI  - Choroidal metastasis from sporadic medullary thyroid carcinoma.

PMID- 16405420
TI  - Lingual thyroid associated with Graves' disease and Graves' ophthalmopathy.

PMID- 16405419
TI  - Completion thyroidectomy and thyroglobulin measurement in the management of
      metastatic differentiated thyroid cancer.

PMID- 16405421
TI  - Computed tomography scan under a trumpet maneuver to demonstrate piriform sinus
      fistulae in patients with acute suppurative thyroiditis.

PMID- 16405422
TI  - Locally advanced papillary thyroid carcinoma with coexistent metastasis from
      hepatocellular carcinoma in the thyroid gland and parathyroid adenoma.

PMID- 16405423
TI  - Resection of follicular thyroid cancer metastasized to the left lower lobe of the
      lung extending into the left atrium as a huge intracardiac tumor.

PMID- 16405424
TI  - A large cervical lymph node metastasis from a thoracic esophageal carcinoma
      considered a thyroid carcinoma at the first medical examination.

PMID- 16405427
TI  - The ABC transporter BmrA from Bacillus subtilis is a functional dimer when in a
      detergent-solubilized state.
AB  - BmrA from Bacillus subtilis is a half-size ABC (ATP-binding cassette) transporter
      involved in multidrug resistance. Although its supramolecular organization has
      been investigated after reconstitution in a lipid bilayer environment, and shows
      a dimeric and possibly a tetrameric form, the precise quaternary structure in a
      detergent-solubilized state has never been addressed. In the present study, BmrA
      was purified from Escherichia coli membranes using an optimized purification
      protocol and different detergents. Furthermore, the ATPase activity of BmrA and
      the quantity of bound lipids and detergent were determined, and the oligomeric
      state was analysed using SEC (size-exclusion chromatography) and analytical
      ultracentrifugation. The activity and the quaternary structure of BmrA appeared
      to be strongly influenced by the type and concentration of the detergent used.
      SEC data showed that BmrA could be purified in a functional form in 0.05 and
      0.01% DDM (n-dodecyl-beta-D-maltoside) and was homogeneous and monodisperse with
      an R(s) (Stokes radius) of 5.6 nm that is compatible with a dimer structure.
      Sedimentation-velocity and equilibrium experiments unequivocally supported that
      BmrA purified in DDM is a dimer and excluded the presence of other oligomeric
      states. These observations, which are discussed in relation to results obtained
      in proteoliposomes, also constitute an important first step towards
      crystallographic studies of BmrA structure.

PMID- 16405429
TI  - Evaluation of C-reactive protein, interleukin-6, and procalcitonin levels in
      allogeneic hematopoietic stem cell recipients.
AB  - BACKGROUND: Prompt detection of transplant-related complications (TRC) as
      infections, acute graft-versus-host disease (aGVHD), microangiopathic hemolytic
      anemia, or veno-occlusive disease following allogeneic hematopoietic stem cell
      transplantation (HSCT) is essential. PATIENTS AND METHODS: We conducted a
      prospective trial on clinical significance of C-reactive protein (CRP),
      interleukin-6 (IL-6) and procalcitonin (PCT) serum levels in TRC. A total of 350
      stem cell recipients were admitted. CRP, IL-6 and PCT were analyzed prior to
      conditioning and weekly until 8 wk after HSCT. TRC were recorded weekly
      throughout the study. RESULTS: CRP (4.4 mg/dL vs. 12.8 mg/dL; P < 0.001), IL-6
      (93 ng/mL vs. 1.138 ng/mL; P < 0.001) and PCT (0.8 ng/dL vs. 5.7 ng/dL; P <
      0.001) were increased in infectious complications. Only PCT differentiated
      between infection and other TRC. Exclusive aGVHD did not increase CRP (4.4 mg/dL
      vs. 5.7 mg/dL; n.s.), IL-6 (93 ng/mL vs. 153 ng/mL; n.s.) and PCT (0.8 ng/dL vs.
      0.8 ng/dL; n.s.). CRP (6.1 mg/dL vs. 3.1 mg/dL; P < 0.001) and IL-6 (295 ng/mL
      vs. 122 ng/mL; P = 0.001) were decreased during steroid therapy, but not PCT (2.3
      ng/dL vs. 2.0 ng/dL; n.s.). CONCLUSION: Our study confirmed CRP, IL-6 and PCT
      serum levels as helpful markers for TRC. PCT can differentiate infection from
      GVHD despite steroid therapy. Further trials are needed focusing on the
      identification of patients who benefit from early risk stratification.

PMID- 16405428
TI  - IkappaB is a sensitive target for oxidation by cell-permeable chloramines:
      inhibition of NF-kappaB activity by glycine chloramine through methionine
      oxidation.
AB  - Hypochlorous acid (HOCl) is produced by the neutrophil enzyme, myeloperoxidase,
      and reacts with amines to generate chloramines. These oxidants react readily with
      thiols and methionine and can affect cell-regulatory pathways. In the present
      study, we have investigated the ability of HOCl, glycine chloramine (Gly-Cl) and
      taurine chloramine (Tau-Cl) to oxidize IkappaBalpha, the inhibitor of NF-kappaB
      (nuclear factor kappaB), and to prevent activation of the NF-kappaB pathway in
      Jurkat cells. Glycine chloramine (Gly-Cl) and HOCl were permeable to the cells as
      determined by oxidation of intracellular GSH and inactivation of glyceraldehyde-3
      phosphate dehydrogenase, whereas Tau-Cl showed no detectable cell permeability.
      Both Gly-Cl (20-200 muM) and HOCl (50 microM) caused oxidation of IkappaBalpha
      methionine, measured by a shift in electrophoretic mobility, when added to the
      cells in Hanks buffer. In contrast, a high concentration of Tau-Cl (1 mM) in
      Hanks buffer had no effect. However, Tau-Cl in full medium did modify
      IkappaBalpha. This we attribute to chlorine exchange with other amines in the
      medium to form more permeable chloramines. Oxidation by Gly-Cl prevented
      IkappaBalpha degradation in cells treated with TNFalpha (tumour necrosis factor
      alpha) and inhibited nuclear translocation of NF-kappaB. IkappaBalpha
      modification was reversed by methionine sulphoxide reductase, with both A and B
      forms required for complete reduction. Oxidized IkappaBalpha persisted
      intracellularly for up to 6 h. Reversion occurred in the presence of
      cycloheximide, but was prevented if thioredoxin reductase was inhibited,
      suggesting that it was due to endogenous methionine sulphoxide reductase
      activity. These results show that cell-permeable chloramines, either directly or
      when formed in medium, could regulate NF-kappaB activation via reversible
      IkappaBalpha oxidation.

PMID- 16405430
TI  - Infections after CD34-selected or unmanipulated autologous hematopoietic stem
      cell transplantation.
AB  - Immune reconstitution may be delayed after CD34-selected compared with
      unmanipulated autologous peripheral blood stem cell transplantation (PBSCT),
      resulting in a theoretically increased risk of infections. In a case-control
      matched study we compared the incidence of infection in 25 recipients of CD34
      selected PBSC (CD34 group) and 75 recipients of unmanipulated PBSC (PBSC group)
      transplants. The population included 52 males and 48 females suffering from non
      Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 8), multiple myeloma (n = 40)
      or breast cancer (n = 20). Neutrophil engraftment was comparable in the two
      groups. The actuarial incidence of infection was similar in the two groups (56%
      vs. 49% at day 30, and 70% vs. 64% at 1 yr respectively). The proportion of
      patients with 1, 2 or 3 infections, the number of infectious event per patient
      (1.32 vs. 1.04; NS), the number of infections before day 15 or 30, between days
      31 and 100 or after day 100, the risk of varicella-zoster virus or
      cytomegalovirus infection or disease, or the use of antibiotic or antifungal
      therapy, were not increased in the CD34 compared with the PBSC group. The main
      agents responsible for infection were bacteria, particularly gram-positive cocci,
      in both groups. Bacteremia accounted for 33% of all infectious events in the CD34
      group vs. 16% in the PBSC group (P < 0.05). Fungal infections were rare. In
      conclusion, our results do not support the notion that CD34-selection of the
      graft is associated with an increased rate of infection after autologous PBSC
      transplantation. The role of extended infection prophylaxis should be evaluated.

PMID- 16405431
TI  - Association of Epstein-Barr virus with human immunodeficiency virus-negative
      peripheral T-cell lymphomas in Japan.
AB  - The association of Epstein-Barr virus (EBV) with human immunodeficiency virus
      negative T-cell lymphoma was examined in 68 patients using the polymerase chain
      reaction (PCR) with DNA obtained from formalin-fixed paraffin-embedded tissues
      and an in situ hybridization technique. EBV-encoded RNA (EBER) was detected in 43
      of 68 cases (63%) of peripheral T-cell lymphoma: in 100% (11 of 11 cases) of NK/T
      cell lymphomas, 70% (14 of 20 cases) of angioimmunoblastic T-cell lymphomas
      (AILT) and 49% (18 of 37 cases) of other types of peripheral T-cell lymphoma. A
      positive band was also detected at high incidence (36 of 65 cases; 55%) in a PCR
      analysis using primers to detect the Bam HI-W fragment of EBV. In the
      immunohistochemical analysis using a monoclonal antibody to latent membrane
      protein 1 (LMP-1) of EBV, one of the EBV-encoded latent gene products, LMP-1, was
      found to be expressed in 13 of 64 cases (20%), but EBNA-2 was not expressed in
      all the cases examined (0 of 59 cases; 0%). The 5-yr survival rate was 28% for
      peripheral T-cell lymphomas overall, 0% for NK/T-cell lymphomas, 38% for AILTs
      and 28% for other types of peripheral T-cell lymphoma. The difference in the
      overall survival rate between NK/T-cell lymphoma and non-NK/T-cell lymphoma was
      significant (P = 0.0498 by Log-rank test). Among peripheral T-cell lymphoma
      patients overall, the group severely infected with EBV (EBER-ISH ++) had a lower
      5-yr survival rate (8%) than the group slightly (EBER-ISH +) or not infected
      (38%; P = 0.0013).

PMID- 16405433
TI  - Multipoint interphase FISH analysis of chromosome 3 abnormalities in 28 childhood
      AML patients.
AB  - We detected non-random 3p losses and 3q gains on well-determined regions in both
      murine and human tumors using a microcell hybrid-based model system called
      'elimination test'. We suggest that these are general malignancy-associated
      aberrations not necessarily linked to a particular tissue of origin. To examine
      chromosome 3 abnormalities, in 28 childhood acute myeloid leukemia bone marrow
      samples, we performed interphase multipoint-fluorescence in situ hybridization
      using 84 chromosome 3-specific probes and detected clonal chromosome 3
      aberrations in nine cases, which is of a higher frequency than the previously
      reported one. In 3/28 children, a chromosome 3 abnormality was detected which was
      not visible using conventional cytogenetic analysis. We did not detect any 3p
      deletion. Increased copy number of 3q was found in four cases with trisomy of
      whole chromosome 3 and one case with 3q tetrasomy (isodisomy). We identified rare
      structural rearrangements in childhood acute myeloblastic leukemia, involving
      3q21 and 3q26 loci around RPN1 and MDS1/EVI1 respectively. The poor outcome in
      pediatric patients with 3q rearrangements appears to be quite uniform.

PMID- 16405432
TI  - Long-term remission in HIV-negative patients with multicentric Castleman's
      disease using rituximab.
AB  - Multicentric Castleman's disease (MCD) is an indolent lymphoproliferative
      disorder. The pathogenesis of MCD has not been established, and its treatment
      remains uncertain. Several authors have described the relationship of human
      herpes virus type 8 (HHV-8) to MCD in human immunodeficiency virus (HIV)-positive
      patients. Recently, anti-CD20 monoclonal antibody (rituximab) is increasingly
      being used to treat HIV-positive MCD; although it is uncertain whether rituximab
      is effective for HIV-negative patients with MCD. To explore the benefit of
      rituximab for HIV-negative patients with MCD, we describe the clinical and
      biologic course in three HIV-negative patients with MCD, and examined the
      relationship of HHV-8 infection to HIV-negative MCD. Their polymerase chain
      reaction analyses for the HHV-8 sequence in peripheral blood were negative, and
      there was no relationship between HHV-8 infection and symptoms of HIV-negative
      MCD. Two of three patients (66%) achieved a near complete remission with no
      clinical symptoms due to MCD with a follow-up of 16-40 months after rituximab
      administration. One of the three patients presented no clinical remission of MCD
      after rituximab administration, although a significant decrease of inflammatory
      parameters was observed. These findings suggest that rituximab treatment may be
      an appropriate first-line therapy for HIV-negative MCD.

PMID- 16405434
TI  - Assessment of the frequency of additional cancers in patients with splenic
      marginal zone lymphoma.
AB  - OBJECTIVES: Solid second primary cancers (SPC) have become an issue of extensive
      research. The purpose of the present study was to estimate the standardised
      incidence ratio (SIR) and the absolute excess risk (AER) of SPC in patients with
      splenic marginal zone lymphoma (SMZL). METHODS: We investigated the incidence of
      additional cancers in 129 patients consecutively diagnosed with SMZL in three
      Italian haematological centres, asking the cooperating doctors for additional
      information on initial and subsequent therapies and on the onset and type of
      second cancers. RESULTS: Twelve SPC were recorded (9.3%); the 3- and 5-yr
      cumulative incidence rates were 5.5% and 18.3% respectively, with an SIR of 2.03
      [95% confidence interval (CI): 1.05-3.56; P < 0.05; AER = 145.81]. Of 12 SPC
      observed, four were urinary tract neoplasms (SIR, 3.70; 95% CI: 1.01-9.48; P <
      0.05; AER = 70.06), four were lung cancers (SIR, 9.16; 95% CI: 1.41-13.25; P <
      0.05; AER = 85.50) and the other four were hepatic carcinoma, endometrial cancer,
      breast cancer and colorectal cancer. CONCLUSIONS: Our findings evidence a high
      frequency of additional cancers in patients with SMZL and suggest that the
      incidence rate of SPC is significantly different from that expected in the
      general population. The frequency of cases with urinary tract and lung
      malignancies in our series is higher than expected. Although confirmatory data
      are needed, it is our opinion that SMZL patients are at risk of second cancer and
      should be carefully investigated on diagnosis and monitored during the follow-up.

PMID- 16405435
TI  - Focal MIBI uptake is a better indicator of active myeloma than diffuse uptake.
AB  - PURPOSE: Technetium-99m 2-methoxyisobutylisonitrile (MIBI) imaging has been
      proposed as a front-line investigation to detect bone disease both before and
      after the treatment of myeloma. In this study, we have compared the pattern of
      MIBI uptake (focal and diffuse) between patients with proven myeloma and a cohort
      of patients without myeloma, in order to identify the uptake pattern that best
      correlates with disease activity. METHODS: Nineteen scans were taken in 16
      consecutive patients (nine males and seven females: aged 39-71 yr) with active
      myeloma. A further 20 scans (10 subjects having MIBI myocardial perfusion
      scintigraphy and 10 subjects having MIBI parathyroid adenoma localisation
      studies), comprised the control (non-myeloma) cohort. Scans were evaluated in a
      double-blinded fashion by two observers for any diffuse skeletal MIBI uptake
      (homogeneous uptake in spine, sternum and/or long bones), and/or abnormal focal
      uptake (patchy, focal or tubular uptake in the skeleton or soft tissues).
      RESULTS: The pattern of MIBI uptake was significantly different in the myeloma
      positive subjects and the control cohort. Focal uptake was highly discriminatory,
      being seen in 15 of 19 (79%) scans of the myeloma-positive group as opposed to
      one of 20 (5%) scans of the control group (P < 0.0001). In contrast, diffuse
      uptake was seen in 17 of 19 (89%) scans in patients with myeloma, and in 11 of 20
      (55%) of the control cohort (P = 0.02). Using multiple logistic regression
      analysis, any focal uptake was significantly predictive for active myeloma (P =
      0.0007) but diffuse uptake was not (P = 0.15). Diffuse uptake alone, without
      focal uptake, was found in four of 19 scans with myeloma and in 10 of 20 without
      active myeloma, but was not significantly associated with absence of active
      myeloma (P = 0.06). Using the criteria of Pace et al. for positivity (diffuse
      activity >50% myocardial activity), we demonstrated improved specificity from 45%
      to 100%, but significantly impaired sensitivity for presence of myeloma (79% vs.
      37%, P = 0.02). CONCLUSION: Our study thus illustrates that the presence of any
      focal uptake of MIBI is useful in indicating active myeloma whereas diffuse
      uptake is not.

PMID- 16405436
TI  - Technetium 99m-diethylene triamine penta-acetic acid aerosol clearance in the
      evaluation of pulmonary involvement in sickle cell disease.
AB  - BACKGROUND: Pulmonary clearance of inhaled technetium (Tc) 99m-labeled diethylene
      triamine penta-acetic acid (DTPA) aerosol is a sensitive non-invasive marker of
      alveolar permeability and patients with interstitial lung diseases show enhanced
      clearance. However, a previous study in adult patients with diabetes mellitus
      showed delayed clearance. OBJECTIVES: To investigate DTPA clearance in steady
      state, otherwise healthy adult sickle cell disease (SCD) patients and correlate
      it with pulmonary function tests (PFTs), hematologic and clinical parameters.
      MATERIALS AND METHODS: The subjects were randomly selected from the Hematology
      Clinic of Mubarak Hospital, Kuwait. Hematologic and pulmonary function data were
      collected with standard methods. DTPA radio-aerosol clearance studies were
      performed using ultrafine nebulizer containing 35 mCi (1295 MBq) of Tc 99m-DTPA
      in its reservoir and t(1/2) clearance in minutes was determined. Average values
      for both lungs were calculated and compared with normal values for our
      population. RESULTS: Forty-three subjects (24 SS and 19 S-beta(0)thal) aged
      between 16 and 45 yr (mean of 27.1 +/- 9.7) were studied. Twenty-two subjects
      (51.2%) had delayed, while only 10 (23.3%) showed enhanced DTPA clearance.
      Patients with enhanced clearance showed better PFTs than those with normal or
      delayed clearance. There was significant negative correlation of DTPA clearance
      with forced expiratory volume in 1 s, forced vital capacity and total lung
      capacity and significant positive correlation with age. CONCLUSIONS: Majority of
      adult SCD patients have delayed DTPA clearance unlike in inflammatory lung
      diseases, but similar to diabetes mellitus. DTPA clearance may be a useful
      modality for monitoring pulmonary involvement in SCD.

PMID- 16405438
TI  - Resistant pure red cell aplasia after allogeneic bone marrow transplantation with
      major ABO mismatch treated by purified CD34+ cell infusion.
AB  - We report a case of pure red cell aplasia (PRCA) subsequent to an allogeneic bone
      marrow transplantation with a major ABO mismatch, which was resistant to the
      standard treatment options such as plasma exchange, erythropoietin and changes in
      the immunosuppressive treatment. Accordingly, two cycles of Rituximab therapy
      were administered without success. The patient had a chronic graft-vs.-host
      disease of the liver, which meant that an additional donor leukocyte infusion
      could not be introduced. Instead, purified CD34(+) cells were administered after
      fludarabine and antithymocyte globulin therapy. As a result, the PRCA was
      resolved and the antidonor isohemagglutinin titer became undetectable.

PMID- 16405437
TI  - Effects of IgG and its F(ab')2 fragments of some patients with idiopathic
      thrombocytopenic purpura on platelet aggregation.
AB  - OBJECTIVES: To make humanized monoclonal antibodies by phage surface display
      technology, we screened out the specific anti-platelet glycoproteins (GPs) IgG
      antibody from patients with chronic idiopathic thrombocytopenic purpura (ITP),
      which can inhibit platelet aggregation. METHODS: We studied plasmas from 68
      patients with ITP for the presence of IgG antibodies specific for GPIIb/IIIa
      and/or GPIb/IX using modified monoclonal antibody immobilization of platelet
      antigen assays. The IgG antibody and its F(ab')(2) fragments of the positive
      plasmas which could inhibit platelet aggregation function were prepared and
      purified. Their immunoreactivity to platelet GPs and effects on platelet function
      were further analyzed. RESULTS: GPIIb/IIIa- and GPIb/IX-specific antibodies were
      found in 21 and 19 patients, respectively. Six of them had antibodies against
      both GP complexes. Among the 34 positive plasmas, four with positive anti
      GPIIb/IIIa autoantibody showed significant inhibition of platelet aggregation
      induced by adenosine diphosphate (ADP), whereas one with GPIb/IX-specific
      antibody inhibited ristocetin-induced platelet aggregation. The purified IgG and
      its F(ab')(2) fragments from two patients not only retained the ability to bind
      to platelet GPs but also impaired the in vitro ADP-induced platelet aggregation.
      CONCLUSIONS: F(ab')(2) portion of the IgG is a functional fragment, which is
      responsible for the autoantibody interaction with platelet GPs in ITP, and some
      of them also affect platelet function, which can be used to develop completely
      humanized anti-GPIIb/IIIa small molecular phage antibody.

PMID- 16405439
TI  - A unique case of acute promyelocytic leukemia showing monocytic differentiation
      after ATRA (all-trans retinoic acid) therapy.
AB  - Acute promyelocytic leukemia (PML) is characterized by a reciprocal translocation
      between chromosomes 15 and 17 resulting in a chimeric PML and retinoic acid
      receptor alpha (RARA) oncogene. The resultant fusion protein (PML/RARA) is
      thought to block differentiation of bone marrow cells arrested at the
      promyelocytic stage. In vitro and in vivo studies have shown that the large
      majority of APL cells undergo granulocytic maturation after ATRA therapy. We
      report a unique case of a PML/RARA positive APL patient exhibiting extensive
      monocytic differentiation after ATRA therapy as documented by morphology, flow
      cytometry, and FISH studies. We discuss potential dual capability for
      granulocytic/monocytic differentiation of PML/RARA positive APL cells and
      implications of monocytic differentiation in the management of APL patients
      treated with ATRA.

PMID- 16405440
TI  - Primary sclerosing cholangitis complicating plasma cell dyscrasia (PCD):
      remission of PCD following liver transplant.
AB  - We report the first case of primary sclerosing cholangitis (PSC) complicated with
      plasma cell dyscrasia (PCD) in which liver transplant resulted in unexpected
      therapeutic benefit of PCD. A 61-year-old man with 12 yr history of PSC presented
      with a monoclonal gammopathy of undetermined significance (MGUS) with an IgG
      level of 3400 mg/dL. It was stable initially for 3 yr but progressed to features
      consistent with multiple myeloma (MM): IgG rose to 5290 mg/dL along with
      development of terminal stage of liver failure. Liver transplant was performed in
      desperation. Unexpectedly, MM underwent clinical remission following transplant.
      At 3 and 14 months following transplant, IgG stayed below 2080 mg/dL and he was
      able to return to full-time employment. This case may suggest that chronic
      antigenic stimulation from cirrhotic liver contributed to MGUS and subsequent
      transformation to MM. Liver transplant eliminated chronic antigenic stimulation,
      apparently leading to remission of MM. Since PCD is often associated with other
      chronic liver diseases, similar benefit may accrue to a range of patients with
      chronic liver diseases complicating PCD.

PMID- 16405441
TI  - Chronic gingivitis in a new BTK mutation.
AB  - A 5-yr-old Caucasian boy with a new mutation in Bruton's tyrosine kinase (BTK) is
      described. Full sequencing of the BTK gene revealed a point mutation in exon 17
      resulting in an amino acid change from tryptophan to serine at location 581 of
      the tyrosine kinase domain. Clinically the child presented with chronic
      gingivitis and had no prior history of bacterial infections. Whereas serum
      immunoglobulin M (IgM) levels were undetectable, IgG levels were in the low
      normal range. The gingivitis completely resolved after intravenous immunoglobulin
      therapy. Lymphocyte phenotyping revealed 0.05% B cells in his peripheral blood,
      which were IgG(-), IgM(+), IgD(+), CD38(+), CD20(+), CD27(-). However, 40% of the
      B cells also expressed CD5. This subpopulation of B cells has not previously been
      described in X-linked agammaglobulinaemia (XLA) patients. We suggest that the
      occurrence of CD5(+) B cells could correlate with a late onset and mild clinical
      presentations of XLA.

PMID- 16405442
TI  - Delayed effusive pericarditis and recurrent pleural effusion after radiation
      treatment for Hodgkin's disease responsive to per os doxycycline.
AB  - We present our experience with a patient with effusive pericarditis and recurrent
      pleural effusion that first developed 23 yr after radiation treatment for the
      nodular sclerosis type of Hodgkin's disease. Extensive diagnostic work up
      including pericardial and pleural biopsy, excluded any other cause (than
      radiation) of the recurrent pleural effusion. Pericarditis and pleural effusion
      were not controlled with regimens including steroid and non-steroid anti
      inflammatory agents. The fluid collections improved only with per os doxycycline
      (100 mg twice a day). Four episodes of recurrent pleural effusions were also
      controlled with per os doxycycline. Although the concentration of doxycycline in
      the pericardial and pleural fluid when given orally is smaller compared with that
      achieved by direct installation of the agent, the fact that all episodes of
      pleural effusion improved with an agent commonly used for pleurodesis is
      intriguing.

PMID- 16405443
TI  - Percutaneous vertebroplasty and kyphoplasty in patients with multiple myeloma.

PMID- 16405445
TI  - Normovolaemia defined by central blood volume and venous oxygen saturation.
AB  - 1. The intravenous administration of fluid and blood has to balance the danger of
      unexpected death in response to a reduction of central blood volume (CBV) against
      that of developing pulmonary and/or peripheral oedema. 2. The initial
      cardiovascular response to haemorrhage is similar to that developed in response
      to standing. In the upright position, adults are subjected to a reduction of CBV
      of approximately 0.5 L and can therefore tolerate a blood loss of approximately 1
      L when supine. 3. However, volume administration directed by cardiovascular
      variables is seldom precise, even with integration of the bradycardia and
      hypotension developed when CBV decreases by approximately 30%. Immediate
      intervention is needed because such a reduction in CBV raises the lower limit of
      cerebral autoregulation to approximately 80 mmHg compared with the commonly
      considered value of approximately 60 mmHg with an associated risk of developing
      brain ischaemia and irreversible shock. 4. Alternatively, the volume load can be
      monitored both directly and accurately by means of thoracic electrical
      admittance. A functional definition of normovolaemia may be the filling of the
      heart that ensures cardiac output and oxygen delivery. From that perspective,
      supine humans are normovolaemic in that a maximal venous oxygen saturation (Svo2)
      is established. 5. Conversely, Svo2 decreases in the upright position and, with a
      blood loss of approximately 100 mL, Svo2 is reduced by 1%. It is suggested that,
      in supine humans and guided by Svo2, normovolaemia may be established to an
      accuracy of approximately 100 mL and that its adequacy is controlled by recording
      cerebral oxygenation.

PMID- 16405446
TI  - Contribution of baroreflex sensitivity and vascular reactivity to variable
      haemodynamic responses to cocaine in conscious rats.
AB  - 1. Baroreflex function is critical for short-term arterial pressure regulation
      and decreased baroreflex responsivity may predict a predisposition to
      hypertension and sudden cardiac death. In the present study, we assessed whether
      baroreflex sensitivity (BRS) and/or vascular reactivity covary with haemodynamic
      responsiveness to cocaine in vascular and mixed responders. 2. We assessed the
      heart rate index of BRS in resting animals. We examined dose-response
      relationships to pressor and depressor agents to determine cardiovascular
      reactivity. Subsequently, rats were given cocaine (5 mg/kg, i.v.) to classify
      them as vascular or mixed responders. Vascular responders (n=16) were defined as
      those rats with a substantial (>8%) decrease in cardiac output in response to
      cocaine owing to a larger increase in systemic vascular resistance. The remaining
      rats (n=8) were mixed responders because they had smaller increases in vascular
      resistance and little change or an increase in cardiac output. 3. The BRS
      determined with angiotensin (Ang) II, but not with phenylephrine, was impaired in
      mixed responders compared with vascular responders. At equipressor doses, there
      were significantly greater reductions in cardiac output in vascular responders
      compared with mixed responders in response to phenylephrine or AngII.
      Methacholine produced greater decreases in heart rate in vascular responders,
      suggesting greater muscarinic responsivity. 4. We conclude that differences in
      vascular reactivity to AngII may contribute to differences in haemodynamic
      response profiles to cocaine in individual rats. More importantly, the
      differences in vascular responsivity and BRS do not appear to be primary
      determinants of haemodynamic response variability.

PMID- 16405447
TI  - Effects of glitazones on blood pressure and vascular structure in mesenteric
      resistance arteries and basilar artery from genetically hypertensive rats.
AB  - 1. The effects of two of the glitazone (thiazolidinedione) class of drugs, namely
      rosiglitazone and pioglitazone, on blood pressure and vascular remodelling in the
      New Zealand genetically hypertensive (GH) rat model were investigated. 2. In the
      first study, a GH group given rosiglitazone (5 mg/kg per day) from the age of 7
      to 12 weeks was compared with a GH control group. In the second study, GH rats
      were given either pioglitazone, simvastatin, valsartan or combinations of
      pioglitazone with simvastatin or valsartan (all drugs at a dose of 10 mg/kg per
      day). 3. Tail-cuff systolic blood pressure was measured weekly. At the end of the
      experiment, blood vessels were fixed by perfusion and samples of mesenteric
      resistance arteries (MRA), second-order branches and basilar artery were embedded
      in Technovit and serial sections were cut and stained with Giemsa for
      stereological analysis. Media width, medial cross-sectional area and lumen
      diameter were determined and the ratio of media width/lumen diameter was
      calculated. 4. Rosiglitazone significantly reduced blood pressure in GH rats. 5.
      In MRA, rosiglitazone had a hypotrophic effect on media, reduced lumen diameter
      and reduced media/lumen ratio (P<0.001). 6. In basilar artery, there was also a
      hypotrophic effect of rosiglitazone on media and reduced media/lumen ratio
      (P<0.001). 7. Pioglitazone slowed down the rate of blood pressure increase with
      age in GH rats and had a greater effect on blood pressure when given in
      combination with simvastatin. 8. Pioglitazone had a hypotrophic effect on the
      media of MRA and basilar artery. The hypotrophic effect was enhanced when
      pioglitazone was given in combination with simvastatin. The media/lumen ratio was
      reduced by pioglitazone; in MRA, combination treatment with simvastatin reduced
      the ratio further to normal and, with valsartan, to below normal. In basilar
      artery, the media/lumen ratio was reduced further by both combination treatments,
      but was lowest in the pioglitazone-valsartan combination group. 9. The
      significant effects on MRA and basilar artery structure (and, thus,
      haemodynamics) seen after rosiglitazone monotherapy and after pioglitazone, given
      alone and in combination with simvastatin or valsartan, may well indicate a
      glitazone class effect on vascular structure and, hence, cardiovascular function.

PMID- 16405448
TI  - Protective effects of exogenously administered or endogenously produced melatonin
      on hyperbaric oxygen-induced oxidative stress in the rat brain.
AB  - 1. Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases.
      A known side-effect of HBO is the production of reactive oxygen species (ROS).
      Many anti-oxidants, such as vitamins C and E, riboflavin and selenium, have been
      used successfully to scavenge the ROS produced by HBO administration. 2. The aim
      of the present study was to determine whether melatonin, a newly discovered anti
      oxidant, has a protective effect against the overproduction of ROS produced by
      HBO in rat brain tissue. 3. Seventy male Sprague-Dawley rats were divided into
      seven groups as follows: 1, daytime control; 2, daytime HBO; 3, melatonin; 4,
      daytime HBO plus melatonin; 5, night-time control; 6, night-time HBO; and 7,
      night-time HBO under light exposure. 4. Hyperbaric oxygen was administered at 303
      kPa for 120 min. Melatonin was injected at a dose of 10 mg/kg, i.p. Brain
      malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) levels were measured to elucidate oxidant status. 4. The MDA and SOD levels
      of groups 2 and 7 increased significantly. Exogenous (group 4) and endogenous
      (group 6) melatonin protected against HBO-induced lipid peroxidation. Exogenously
      administered melatonin (groups 3 and 4) had increased levels of the anti-oxidant
      enzymes SOD and GPx. 5. In conclusion, HBO caused oxidative stress and melatonin
      exhibited protective effects. Both endogenously produced and exogenously
      administered melatonin were found to be effective.

PMID- 16405449
TI  - Effects of BW245C, a prostaglandin dp receptor agonist, on systemic and regional
      haemodynamics in the anaesthetized rat.
AB  - 1. Prostaglandin D (DP) receptor agonists have been shown to induce hypotension
      in rat models, possibly via peripheral vasodilation. However, it is not known
      which tissues and organs are most responsive. 2. In the present study, BW245C, a
      DP receptor-selective agonist, was administered to Inactin (Sigma, St Louis, MO,
      USA)-anaesthetized rats. Animals received three serial i.v. infusions (17 min
      each) of either BW245C (escalating doses of 0.3, 3 and 30 microg/kg; n=6) or
      vehicle (6% ethanol in normal saline; n=6). Mean arterial pressure (MAP) and
      heart rate were monitored continuously and regional blood flow was determined by
      the radionuclide-labelled microsphere method at baseline and at the end of each
      infusion. 3. It was found that BW245C dose-dependently reduced MAP; blood flow
      increased in forelimb skeletal muscle and skin, resulting in decreases in the
      regional vascular resistance (RVR) of skeletal muscle to -6+/-13, -53+/-11 and 
      68+/-6% of baseline following 0.3, 3 and 30 microg/kg BW245C, respectively
      (P<0.05 vs vehicle treatment for the two higher doses), and skin to -29+/-8, 
      55+/-8 (P<0.05) and -30+/-16% of baseline, respectively. Relative to vehicle,
      blood flow and RVR for brain, heart, lung, liver, stomach and kidney were not
      significantly affected by BW245C. 4. These results demonstrate that the
      hypotension resulting from DP receptor activation in the rat is mediated
      primarily through vasodilation of arterioles of skeletal muscle independent of
      changes in blood flow to vital organs.

PMID- 16405450
TI  - Characterization of two polyclonal peptide antibodies that recognize the carboxy
      terminus of angiotensin II AT1A and AT1B receptors.
AB  - 1. The differential identification of the angiotensin AT1A and AT1B receptor
      subtypes is impaired by the existing>96% homology of both receptors. In the
      present study, we characterized two polyclonal rabbit peptide antibodies, namely
      alpha-AT1A and alpha-AT1B, that recognize the C-terminal region of mouse AT1A and
      AT1B receptors, respectively. 2. In immunoblotting, both antibodies detected two
      major AT1 receptor-specific bands at sizes of 72.5 and 87.6 kDa in mouse tissues
      and in Neuro-2a cell lysates. In immunohistochemistry, antibodies demonstrated
      AT1 receptor-specific staining in renal proximal and distal tubules, as well as
      in kidney glomeruli. In addition, both antibodies stained AT1 receptors in Neuro
      2a cells with G-protein receptor typical distribution. Dot-blot and ELISA
      analysis of the alpha-AT1A antibody showed 2.5- to fourfold higher selectivity
      for its AT1A receptor target peptide (1A-PEP) compared with the non-specific AT1B
      receptor peptide (1B-PEP). In contrast, the alpha-AT1B antibody showed high
      binding affinity towards its target peptide 1B-PEP, but also demonstrated high
      cross-reactivity for the non-specific peptide 1A-PEP (1.4- to twofold in ELISA
      and dot-blot analysis). In contrast with the lack of recognition by the alpha
      AT1B antibody, the alpha-AT1A antibody selectively recognized the AT1A receptor
      fused to red fluorescence protein in transiently transfected Chinese hamster
      ovary cells. 3. In summary, we have generated two new peptide antibodies to the
      mouse AT1A and AT1B receptors (alpha-AT1A and alpha-AT1B), of which the alpha
      AT1A antibody has the capability to distinguish AT1A receptor types in
      immunological approaches.

PMID- 16405451
TI  - Effect of human splenic contraction on variation in circulating blood cell
      counts.
AB  - 1. The human spleen sequesters 200-250 mL densely packed red blood cells. Up to
      50% of this viscous blood is actively expelled into the systemic circulation
      during strenuous exercise or simulated apnoea (breath-hold) diving. The
      contribution of splenic contraction to changes in the circulating volume of red
      blood cells (RBCV), as well as the venous concentration of white blood cells
      (WBC) and platelets (PLT), was investigated following repeated breath-hold
      apnoeas. 2. Eighteen trained apnoea divers and 18 intact and six splenectomized
      subjects without diving experience repeated five maximal apnoeas with face
      immersion in cold water, with 2 min intervals between successive attempts. Venous
      blood samples were taken before and between consecutive apnoeas, as well as at 0,
      10 and 20 min after the last breath hold. Arterial pressure, heart rate and
      transcutaneous partial pressure of oxygen and carbon dioxide were monitored
      continuously. 3. Plasma protein concentration decreased by 5.8, 2.2 and 9% in
      apnoea divers, untrained and splenectomized subjects, respectively, indicating an
      expansion of plasma volume. The RBCV and venous concentration of WBC, corrected
      for changes in plasma volume, increased in both trained apnoea divers (4.9+/-1.0
      and 14.9+/-3.1%, respectively) and intact subjects (1.7+/-0.8 and 7.2+/-1.8%,
      respectively), whereas in splenectomized subjects there was no change in RBCV and
      a delayed increase in WBC concentration. Furthermore, an initial lymphocytosis
      detected during repeated breath holds in divers and intact subjects was
      completely absent in splenectomized subjects. None of the groups showed
      significant changes in PLT concentrations. The well-recognized diving response to
      apnoea (bradycardia and increased blood pressure) was seen during all breath-hold
      attempts in all subjects. 4. Repeated breath-holds (apnoeas) contribute to
      increased RBCV and venous blood concentrations of WBC through splenic
      contraction.

PMID- 16405452
TI  - Exogenous nitric oxide centrally enhances pulmonary reactivity in the normal and
      hypertensive rat.
AB  - 1. Chronic hypoxia causes sustained pulmonary hypertension and, although
      impairment of the pulmonary endothelial nitric oxide (NO) pathway has been
      implicated, no study has described the central role of NO in modulating pulmonary
      vascular tone and reactivity. Centrally, NO inhibits sympathetic outflow, so we
      hypothesised that central NO would modulate pulmonary vascular tone and its
      reactivity to acute hypoxia, especially in the hypertensive state. 2. Male adult
      Sprague-Dawley rats were exposed to normoxia (N) or chronic hypoxia (CH; 12% O2)
      for 14 days. Mean pulmonary arterial pressure (MPAP), systemic mean arterial
      blood pressure (MABP), cardiac output and heart rate were then measured in
      pentobarbitone-anaesthetized, artificially ventilated rats. The N and CH rats
      were exposed to acute hypoxia (10% O2 for 4 min) after the
      intracerebroventricular (i.c.v.) administration of artificial cerebrospinal fluid
      (control) and then again after either i.c.v. NG-nitro-L-arginine methyl ester (L
      NAME; 150 microg in 10 microL) or 3-morpholino-sydnonimine hydrochloride (SIN-1;
      100 microg in 10 microL). 3. Chronic hypoxia caused pulmonary hypertension (MPAP
      20+/-1 vs 30+/-1 mmHg in N and CH rats, respectively) and attenuated acute
      hypoxic pulmonary vasoconstriction (HPV). Central inhibition of NO synthesis (by
      l-NAME) did not alter baseline MPAP or the acute HPV in either N or CH rats, but
      it did elevate MABP. The NO donor SIN-1 did not alter baseline MPAP, but it did
      enhance (N rats) or restore (CH rats) the HPV and decreased MABP. 4. The results
      of the present study indicate that central NO has a limited role in the tonic
      modulation of MPAP during normoxia and after chronic hypoxia. However, the acute
      HPV seems to be enhanced by exogenous NO.

PMID- 16405454
TI  - Characteristic dysfunction of stunned myocardium induced by 2,3-butanedione
      monoxime without ischaemia.
AB  - 1. In the present study, we tested the hypothesis that, even in the absence of
      prior ischaemia, 2,3-butanedione monoxime (BDM), an inhibitor of contraction at
      the actin-myosin level, could produce the postischaemic dysfunction
      characteristic of stunned myocardium. 2,3-Butanedione monoxime was injected
      directly into the left anterior descending coronary artery (LAD) before and again
      after myocardial stunning produced by 15 min occlusion of the LAD followed by 30
      min reperfusion. 2. Regional myocardial force, segment shortening and regional
      work were measured in both the LAD-perfused area and the area perfused by the
      circumflex coronary artery, which served as a control area. Regional dysfunction
      produced by BDM injection or ischaemia-reperfusion was assessed quantitatively by
      five parameters: end-diastolic length (EDL), shortening onset delay (delay),
      systolic bulge (bulge), end-shortening time delay (EST) and tail work ratio
      (TWR). 3. It was found that injection of BDM into the LAD caused dyskinesis
      similar to that caused by occlusion-reperfusion. Both displayed elevated EDL and
      marked increases in delay, bulge, EST and TWR; these parameters were
      significantly higher in the dyskinesis caused by BDM injection. Despite
      dysfunctional fibre shortening, intracoronary BDM injection did not reduce
      regional force. 4. Thus, BDM can elicit changes similar to those characteristic
      of postischaemic dysfunction. Because contractility was not impaired, dysfunction
      was apparently caused by disrupting the association between contractile force and
      muscle motion.

PMID- 16405453
TI  - Involvement of brain thromboxane A in hypotension induced by haemorrhage in rats.
AB  - 1. In the present study, we aimed to determine the involvement of brain
      thromboxane A2 (TXA2) in blood pressure decreases evoked by acute and/or graded
      haemorrhage in rats. 2. Sprague-Dawley rats were used throughout the study. Acute
      haemorrhage was achieved by withdrawing a total volume of 2.1 and 2.5 mL
      blood/100 g bodyweight over a period of 10 min. A microdialysis study was
      performed in a hypothalamic area to measure extracellular TXA2 levels. Graded
      haemorrhage was conducted successively by withdrawing carotid arterial blood
      (0.55 mL/100 g bodyweight) over a 10 s period four times (S1-S4) at 5 min
      intervals. Furegrelate (125, 250 and 500 microg), a TXA2 synthase inhibitor, was
      injected intracerebroventricularly (i.c.v.) 60 min before acute or graded
      haemorrhage was initiated. U-46619 (0.5, 1 and 2 microg, i.c.v.), a synthetic
      TXA2 analogue, was administered 5 min before acute haemorrhage (2.1 mL/100 g
      bodyweight). 3. Acute haemorrhage produced a severe and long-lasting decrease in
      blood pressure and had a tendency to increase heart rate. Both haemorrhage
      protocols (2.1 or 2.5 mL/100 g) generated similar approximate twofold increases
      in extracellular hypothalamic TXA2 levels. Intracerebroventricular furegrelate
      (250 microg) pretreatment completely blocked the TXA2 increases induced by acute
      haemorrhage. Furegrelate administration (100, 250 and 500 microg, i.c.v.)
      attenuated the fall in arterial pressure evoked by acute haemorrhage and caused
      significant increases in heart rate at all doses injected. 4. Graded haemorrhage
      progressively lowered arterial pressure and increased plasma vasopressin and
      adrenaline levels in the last period. Furegrelate-injected rats were greatly
      resistant to the hypotensive effect of haemorrhage for all degrees of blood
      removed. Plasma adrenaline and vasopressin levels were significantly elevated in
      furegrelate-pretreated rats compared with the saline-treated group during S2-S3
      and S4, respectively. U-46619 administration caused small but statistically
      significant decreases in arterial pressure induced by haemorrhage. 4. The results
      show that acute hypotensive haemorrhage increases extracellular hypothalamic TXA2
      levels. The increase in brain endogenous TXA2 levels involves a decrease in blood
      pressure evoked by haemorrhage because the blockade of TXA2 synthesis by
      furegrelate pretreatment attenuated the haemorrhagic hypotension. Increases in
      plasma adrenaline and vasopressin levels may mediate this effect.

PMID- 16405455
TI  - Individualized drug and dose: the clinical pharmacologist's calling or curse?
AB  - 1. The role of the clinical pharmacologist is to promote the rational, safe and
      effective use of medicines. This revolves around the notion of variability,
      between and within patients and between and within drugs, in terms of both
      pharmacokinetics and pharmacodynamics. Ideal therapeutics involves tailoring the
      drug and its dosing to the individual patient, taking into account this
      variability. 2. In the 25 years of my membership of the Australasian Society of
      Clinical and Experimental Pharmacologists and Toxicologists, three themes have
      dominated my research: (i) drugs and breast feeding; (ii) aminoglycoside dosing;
      and (iii) pharmacogenetics. In all these, the research has been orientated
      towards identifying factors involved in variability and working towards dose
      individualization based on the understanding of these factors. 3. Our model for
      predicting drug concentrations in milk has assisted not only in estimating the
      safety of drug ingestion via breast milk, but also in the understanding of the
      processes involved in drug transfer. 4. The aminoglycoside studies have assisted
      in the understanding of the basis behind extended interval dosing, leading to a
      model for dose prediction that is widely used, especially in Australasia. 5.
      Pharmacogenetics is a field widely acclaimed as having a huge future in terms of
      individualization of drug therapy. Our early studies in this area lend only
      cautious support to this optimism.

PMID- 16405456
TI  - G-Protein-coupled receptor-protein interactions: basis for new concepts on
      receptor structure and function.
AB  - 1. G-Protein-coupled receptors (GPCRs) constitute a large family of cell surface
      proteins. Their primary function is to transmit extracellular stimuli to
      intracellular signals. It is estimated that the human genome contains more than
      1000 genes that code for proteins of the GPCR structure. These receptors also
      comprise the most important class of therapeutic drug targets. 2. The mechanism
      of GPCR signalling was initially envisioned as involving coupling to the
      heterotrimeric G-proteins only. However, recent developments in the field suggest
      that such a simplistic model cannot be sustained any longer. The emerging view is
      that a wide range of accessory proteins are involved in the regulation of every
      aspect of GPCR activity. 3. G-Protein-coupled receptor-interacting proteins are
      implicated in the regulation of several aspects of GPCR biology, including
      receptor targeting to the respective sites of action, receptor anchoring,
      signalling and receptor desensitization. In some cases (e.g. receptor activity
      modifying proteins), they may contribute to the receptor structure and form a
      part of the ligand-binding domain. 4. These findings have contributed to new
      concepts of cellular organization in which modular protein-protein interactions
      provide a network through which signalling pathways are assembled and controlled.

PMID- 16405458
TI  - Clinical toxicology: clinical science to public health.
AB  - 1. The aims of the present paper are to: (i) review progress in clinical
      toxicology over the past 40 years and to place it in the context of modern health
      care by describing its development; and (ii) illustrate the use of clinical
      toxicology data from Scotland, in particular, as a tool for informing clinical
      care and public health policy with respect to drugs. 2. A historical literature
      review was conducted with amalgamation and comparison of a series of published
      and unpublished clinical toxicology datasets from NPIS Edinburgh and other
      sources. 3. Clinical databases within poisons treatment centres offer an
      important method of collecting data on the clinical effects of drugs in overdose.
      These data can be used to increase knowledge on drug toxicity mechanisms that
      inform licensing decisions, contribute to evidence-based care and clinical
      management. Combination of this material with national morbidity datasets
      provides another valuable approach that can inform public health prevention
      strategies. 4. In conclusion, clinical toxicology datasets offer clinical
      pharmacologists a new study area. Clinical toxicology treatment units and poisons
      information services offer an important health resource.

PMID- 16405457
TI  - Connective tissue growth factor: a role in airway remodelling in asthma?
AB  - 1. Severe persistent asthma is accompanied by structural changes in the airway,
      referred to as remodelling. The mechanisms driving airway remodelling are poorly
      understood. 2. Transforming growth factor (TGF)-beta is increased in the airways
      of patients with asthma. Many of the effects of TGF-beta are mediated by
      connective tissue growth factor (CTGF). 3. Overexpression of CTGF is linked to
      many fibrotic diseases, but its exact role in airway remodelling is unknown. 4.
      Connective tissue growth factor mediates cell adhesion, migration, proliferation,
      survival, extracellular matrix synthesis and has a role in angiogenesis. 5.
      Current asthma therapies do not inhibit CTGF induction. 6. Understanding the
      mechanisms underlying the role of CTGF in airway remodelling may lead to new
      therapeutic strategies for asthma.

PMID- 16405461
TI  - Ground water modeling applications using the analytic element method.
AB  - Though powerful and easy to use, applications of the analytic element method are
      not as widespread as finite-difference or finite-element models due in part to
      their relative youth. Although reviews that focus primarily on the mathematical
      development of the method have appeared in the literature, a systematic review of
      applications of the method is not available. An overview of the general types of
      applications of analytic elements in ground water modeling is provided in this
      paper. While not fully encompassing, the applications described here cover areas
      where the method has been historically applied (regional, two-dimensional steady
      state models, analyses of ground water-surface water interaction, quick analyses
      and screening models, wellhead protection studies) as well as more recent
      applications (grid sensitivity analyses, estimating effective conductivity and
      dispersion in highly heterogeneous systems). The review of applications also
      illustrates areas where more method development is needed (three-dimensional and
      transient simulations).

PMID- 16405459
TI  - The need for translational research on antidotes for pesticide poisoning.
AB  - 1. Pesticide poisoning kills hundreds of thousands of people in the Asia-Pacific
      region each year. The majority of deaths are from deliberate self-poisoning with
      organophosphorus pesticides (OP), aluminium phosphide and paraquat. The current
      response from a public health, medical and research perspective is inadequate. 2.
      There are few proven or effective treatments; in addition, very little clinical
      research has been performed to transfer antidotes shown to work in animal studies
      into clinical practice. 3. The human toxicity of pesticides is poorly studied and
      better information may inform a more sustained and appropriate regulatory
      response. Further understanding may also lead to improvements in diagnosis and
      treatment. 4. The few effective treatments are not being recommended or delivered
      in an optimal and timely fashion to poisoned patients. A regional approach to
      facilitate appropriate pricing, packaging and delivery of antidotes is required.

PMID- 16405462
TI  - Using analytic element models to delineate drinking water source protection
      areas.
AB  - Since 1999, Ohio EPA hydrogeologists have used two analytic element models
      (AEMs), the proprietary software GFLOW and U.S. EPA's WhAEM, to delineate
      protection areas for 535 public water systems. Both models now use the GFLOW2001
      solution engine, integrate well with Geographic Information System (GIS)
      technology, have a user-friendly graphical interface, are capable of simulating a
      variety of complex hydrogeologic settings, and do not rely upon a model grid.
      These features simplify the modeling process and enable AEMs to bridge the gap
      between existing simplistic delineation methods and more complex numerical
      models. Ohio EPA hydrogeologists demonstrated that WhAEM2000 and GFLOW2000 were
      capable of producing capture zones similar to more widely accepted models by
      applying the AEMs to eight sites that had been previously delineated using other
      methods. After the Ohio EPA delineated protection areas using AEMs, more
      simplistic delineation methods used by other states (volumetric equation and
      arbitrary fixed radii) were applied to the same water systems to compare the
      differences between various methods. GIS software and two-tailed paired t-tests
      were used to quantify the differences in protection areas and analyze the data.
      The results of this analysis demonstrate that AEMs typically produce
      significantly different protection areas than the most simplistic delineation
      methods, in terms of total area and shape. If the volumetric equation had been
      used instead of AEMs, Ohio would not have protected 265 km2 of critical
      upgradient area and would have overprotected 269 km2 of primarily downgradient
      land. Since an increasing number of land-use restrictions are being tied to
      drinking water protection areas, this analysis has broad policy implications.

PMID- 16405463
TI  - The AEM and regional carbonate aquifer modeling.
AB  - The analytic element method (AEM) has been applied to a 15,000-km2 area of the
      Paleozoic carbonate rock terrain of Nevada. The focus is the Muddy River springs
      area, which receives 1.44 m3/s (51 ft3/s) of regionally derived ground water, and
      forms the Muddy River. The study was undertaken early in 2000 to support the
      development of a cooling water supply for a gas-fired generation facility 20 km
      south of the Muddy River springs. The primary objectives of the AEM modeling were
      to establish a better understanding of regional fluxes and boundary conditions
      and to provide a framework for examination of more local transient effects using
      MODFLOW. Geochemical evidence available in 2000 suggested two separate flow
      fields, one in the north discharging at the springs, and a southern area of small
      hydraulic gradients. To be conservative, however, hydraulic continuity between
      the two areas was maintained in the 2000 AEM model. Using new monitoring well
      data collected in the south, and analyses confirming that seasonal pumping
      effects in the north are not propagated to the south, a later AEM model that
      included a barrier calibrated with relative ease. The analytic element model was
      well suited for simulating an area larger than the immediate area of interest,
      was easy to modify as more information became available, and facilitated the
      stepwise development of multiple conceptual models of the site.

PMID- 16405464
TI  - A multiscale investigation of ground water flow at Clear Lake, Iowa.
AB  - Ground water flow was investigated at Clear Lake, a 1468-ha glacial lake in north
      central Iowa, as part of a comprehensive water quality study. A multiscale
      approach, consisting of seepage meters (and a potentiomanometer), Darcy's law,
      and an analytic element (AE) model, was used to estimate ground water inflow to
      and outflow from the lake. Estimates from the three methods disagreed. Seepage
      meters recorded a median-specific discharge of 0.25 mum/s, which produced a lake
      inflow rate between 90,750 and 138,200 m3/d, but no detectable outflow. A wave
      induced Bernoulli effect probably compromised both inflow and outflow
      measurements. Darcy's law was applied to 11 zones around the lake, producing
      inflow and outflow values of 10,500 and 5000 m3/d, respectively. The AE model,
      GFLOW, coupled with the parameter estimation model, UCODE, simulated ground water
      flow in a 700-km2 region using 31 hydraulic head and base flow measurements as
      calibration targets. The model produced ground water inflow and outflow rates of
      14,300 and 9200 m3/d, respectively. Although not a substitute for field data, the
      model's ability to simulate ground water flow to the lake and the region,
      estimate uncertainty for model parameters, and calculate a lake stage and
      associated lake water balance makes it a powerful tool for water quality
      management and an attractive alternative to the traditional methods of ground
      water/lake investigation.

PMID- 16405465
TI  - Estimating recharge rates with analytic element models and parameter estimation.
AB  - Quantifying the spatial and temporal distribution of recharge is usually a
      prerequisite for effective ground water flow modeling. In this study, an analytic
      element (AE) code (GFLOW) was used with a nonlinear parameter estimation code
      (UCODE) to quantify the spatial and temporal distribution of recharge using
      measured base flows as calibration targets. The ease and flexibility of AE model
      construction and evaluation make this approach well suited for recharge
      estimation. An AE flow model of an undeveloped watershed in northern Wisconsin
      was optimized to match median annual base flows at four stream gages for 1996 to
      2000 to demonstrate the approach. Initial optimizations that assumed a constant
      distributed recharge rate provided good matches (within 5%) to most of the annual
      base flow estimates, but discrepancies of >12% at certain gages suggested that a
      single value of recharge for the entire watershed is inappropriate. Subsequent
      optimizations that allowed for spatially distributed recharge zones based on the
      distribution of vegetation types improved the fit and confirmed that vegetation
      can influence spatial recharge variability in this watershed. Temporally, the
      annual recharge values varied >2.5-fold between 1996 and 2000 during which there
      was an observed 1.7-fold difference in annual precipitation, underscoring the
      influence of nonclimatic factors on interannual recharge variability for regional
      flow modeling. The final recharge values compared favorably with more labor
      intensive field measurements of recharge and results from studies, supporting the
      utility of using linked AE-parameter estimation codes for recharge estimation.

PMID- 16405466
TI  - The synergistic powers of AEM and GIS geodatabase models in water resources
      studies.
AB  - Comprehensive studies of water resources systems require integration of modeling
      tools and data associated with individual processes. An object-oriented approach
      is presented here that associates ground water models based upon the analytic
      element method (AEM) with geographic information system (GIS) geodatabase
      features using an AEM Model Interface. Each aquifer object contains a prescribed
      geometry, a mathematical representation in the AEM, and GIS hydrogeologic data.
      The synergistic understanding inherent in such an approach is illustrated by a
      study linking local AEM model predictions of water elevation with ground water
      geodatabase objects. This AEM Model Interface provides a key component in
      establishing a common object-oriented geodatabase modeling approach linking
      ground water to a variety of natural and social processes.

PMID- 16405467
TI  - Identification of heterogeneous aquifer transmissivity using an AE-based method.
AB  - Determination of hydraulic head, H, as a function of spatial coordinates and
      time, in ground water flow is the basis for aquifer management and for prediction
      of contaminant transport. Several computer codes are available for this purpose.
      Spatial distribution of the transmissivity, T(x,y), is a required input to these
      codes. In most aquifers, T varies in an erratic manner, and it can be
      characterized statistically in terms of a few moments: the expected value, the
      variance, and the variogram. Knowledge of these moments, combined with a few
      measurements, permits one to estimate T at any point using geostatistical
      methods. In a review of transmissivity data from 19 unconsolidated aquifers,
      Hoeksema and Kitanidis (1985) identified two types of the logtransmissivity Y=
      ln(T) variations: correlated variations with variance sigma2Yc and correlation
      scale, I(Y), on the order of kilometers, and uncorrelated variations with
      variance sigma2Yn. Direct identification of the logtransmissivity variogram,
      Gamma(Y), from measurements is difficult because T data are generally scarce.
      However, many head measurements are commonly available. The aim of the paper is
      to introduce a methodology to identify the transmissivity variogram parameters
      (sigma2Yc, I(Y), and sigma2Yn) using head data in formations characterized by
      large logtransmissivity variance. The identification methodology uses a
      combination of precise numerical simulations (carried out using analytic element
      method) and a theoretical model. The main objective is to demonstrate the
      application of the methodology to a regional ground water flow in Eagle Valley
      basin in west-central Nevada for which abundant transmissivity and head
      measurements are available.

PMID- 16405468
TI  - Vertically integrated flows, discharge potential, and the Dupuit-Forchheimer
      approximation.
AB  - We summarize observations made by various researchers regarding the discharge
      potential, vertically integrated flows, and the Dupuit-Forchheimer approximation.
      If a regional flow model is formulated in terms of the discharge potential and
      the boundary conditions can be written in terms of the discharge potential and
      the boundary discharges, then the discharges are correct throughout the model
      domain, without embracing any additional simplifying assumptions.

PMID- 16405469
TI  - The nested superblock approach for regional-scale analytic element models.
AB  - A new approach is presented for improving the computational efficiency of
      regional-scale ground water models based on the analytic element method (AEM).
      The algorithm is an extension of the existing "superblock" algorithm, which
      combines the effects of multiple analytic elements into Laurent series and Taylor
      series (superblock expansions). With the new "nested superblock" formulation,
      Laurent series are nested in a hierarchical (quad-tree) data structure with
      direct mathematical relationships between parent and child superblock
      coefficients. Nested superblocks significantly accelerate the evaluation of the
      complex potential and discharge function in models that contain a large number of
      analytic elements at multiple scales. This evaluation process, the primary
      computational cost of AEM models, is required to determine the element
      coefficients, generate contour plots, and trace pathlines. The performance of the
      nested superblocks is demonstrated with a simplified model based on the Lake
      Ontario watershed geometry comprising thousands of hydrogeologic features at
      multiple geographic scales.

PMID- 16405470
TI  - Analytic element modeling of embedded multiaquifer domains.
AB  - An analytic element approach is presented for the modeling of multiaquifer
      domains embedded in a single-aquifer model. The inside of each domain may consist
      of an arbitrary number of aquifers separated by leaky layers. The analytic
      element solution is obtained through a combination of existing single-aquifer and
      multiaquifer analytic elements and allows for the analytic computation of head
      and leakage at any point in the aquifer. Along the boundary of an embedded
      multiaquifer domain, the normal flux is continuous everywhere; continuity of head
      across the boundary is met exactly at collocations points and approximately, but
      very accurately, in between. The analytic element solution compares well with an
      existing exact solution. A hypothetical example with a river intersecting two
      embedded domains illustrates the practical application of the proposed approach.

PMID- 16405471
TI  - Uniform head in horizontal and vertical wells.
AB  - The steady-state head within a fully penetrating well may be estimated by
      evaluating the Thiem equation at the radius of the well. A method is presented
      here to extend results from the Thiem equation to horizontal wells and to
      partially penetrating wells. The particular model used in this investigation is
      based upon the analytic element method; it accurately reproduces a boundary
      condition of uniform head along the cylindrical surface at the perforated face of
      the well. This model is exercised over a representative range of parameters
      including the well's length, radius, and pumping rate, and the aquifer's
      hydraulic conductivity and thickness. Results are presented in a set of figures
      and tables that compare the well's drawdown to the drawdown that would have been
      obtained using the Thiem solution with the same pumping rate and radius. A
      methodology is presented to estimate the head within a horizontal or partially
      penetrating well by adding a correction term to results that can be readily
      obtained from computer models of vertical fully penetrating wells. This approach
      may also be used to contrast the differences in head between horizontal and
      vertical wells of various lengths, radii, and placement elevations.

PMID- 16405472
TI  - The development of new analytic elements for transient flow and multiaquifer
      flow.
AB  - We deal in this paper with an ongoing development of the analytic element method.
      We present in outline new analytic line elements that are suitable to model
      general flow fields, i.e., flow fields that possess a continuously varying areal
      inflow or outflow. These elements are constructed specifically to model the
      leakage through leaky layers that separate aquifers in leaky systems and to model
      transient effects. The leakage or release from storage underneath linear features
      is modeled precisely by the new elements; the singularity in leakage is matched
      exactly by the approximate solution. Applications are given for a problem
      involving leakage and for a case of transient flow. We note that the analytic
      elements can be used also to reproduce the effect of continuously varying aquifer
      properties, e.g., the hydraulic conductivity or the elevation of the base of the
      aquifer. In the latter case, the elements would reproduce the rotation of the
      flow field caused by the variation in properties, rather than the divergence as
      for the case of leakage.

PMID- 16405473
TI  - Exact solution for two-dimensional flow to a well in an anisotropic domain.
AB  - Although most current applications of the analytic element method are formulated
      for isotropic hydraulic conductivity, anisotropic domains can be modeled with
      analytic elements using the well-known coordinate transformation where one
      coordinate axis is scaled by the square root of the anisotropy ratio. If the
      standard analytic solution for steady radial flow to a well is used with this
      coordinate transformation, the resulting solution correctly models the far field
      but it does not meet the constant head boundary condition at the well radius.
      This could be a significant shortcoming if you are interested in the flow field
      close to the well or want to estimate the head at the pumping well. A new
      solution for two-dimensional steady flow to a well in an anisotropic domain is
      presented. This solution satisfies the governing equations exactly and meets the
      constant head boundary condition at the well radius exactly. It was derived using
      a conformal mapping.

PMID- 16405474
TI  - A fast direct solution method for nonlinear equations in an analytic element
      model.
AB  - The analytic element method, like the boundary integral equation method, gives
      rise to a system of equations with a fully populated coefficient matrix. For
      simple problems, these systems of equations are linear, and a direct solution
      method, such as Gauss elimination, offers the most efficient solution strategy.
      However, more realistic models of regional ground water flow involve nonlinear
      equations, particularly when including surface water and ground water
      interactions. The problem may still be solved by use of Gauss elimination, but it
      requires an iterative procedure with a reconstruction and decomposition of the
      coefficient matrix at every iteration step. The nonlinearities manifest
      themselves as changes in individual matrix coefficients and the elimination (or
      reintroduction) of several equations between one iteration and the other. The
      repeated matrix reconstruction and decomposition is computationally intense and
      may be avoided by use of the Sherman-Morrison formula, which can be used to
      modify the original solution in accordance with (small) changes in the
      coefficient matrix. The computational efficiency of the Sherman-Morrison formula
      decreases with increasing numbers of equations to be modified. In view of this,
      the Sherman-Morrison formula is only used to remove equations from the original
      set of equations, while treating all other nonlinearities by use of an iterative
      refinement procedure.

PMID- 16405475
TI  - Building pit dewatering: application of transient analytic elements.
AB  - Analytic elements are well suited for the design of building pit dewatering.
      Wells and drains can be modeled accurately by analytic elements, both nearby to
      determine the pumping level and at some distance to verify the targeted drawdown
      at the building site and to estimate the consequences in the vicinity. The
      ability to shift locations of wells or drains easily makes the design process
      very flexible. The temporary pumping has transient effects, for which transient
      analytic elements may be used. This is illustrated using the free, open-source,
      object-oriented analytic element simulator Tim(SL) for the design of a building
      pit dewatering near a canal. Steady calculations are complemented with transient
      calculations. Finally, the bandwidths of the results are estimated using linear
      variance analysis.

PMID- 16405476
TI  - Development of an analytic element ground water model of the Netherlands.

PMID- 16405477
TI  - Surgical treatment of basal cell carcinomas using standard postoperative
      histological assessment.
AB  - SUMMARY Surgical treatment of basal cell carcinomas using postoperative
      histological assessment is routinely practised in Australia. The efficacy of the
      procedure depends on key decisions made by the surgeon. The first is case
      selection that requires an understanding of the limitations of the procedure. The
      tumour border is then identified and a margin added. The margin selected should
      achieve the desired balance between incomplete excision rate and mean tissue
      sacrifice. There is an inverse relationship between these parameters; achieving a
      5% incomplete excision rate requires a mean tissue sacrifice of over 4 mm.
      Factors affecting margin selection are discussed, unfortunately none allows a
      dramatic reduction in mean tissue sacrifice. The final decision involves
      interpreting and acting on the histological examination of the excised specimen.
      Tumour recurrence is rare (less than 2% at 5 years) if the tumour is clear of the
      surgical margin. The visualized histological margin required to ensure complete
      excision varies with histological technique and tumour properties. Routine
      reporting of histological margin in millimetres or horizontal sectioning is
      recommended. Tumour recurrence averages 38% when the histological margin is
      involved. The merits of careful clinical follow up of incompletely excised
      tumours or immediate re-excision are discussed.

PMID- 16405478
TI  - Cutaneous lupus erythematosus: a personal approach to management.
AB  - SUMMARY Skin disease in patients with lupus erythematosus may be subdivided into
      two broad categories - those lesions that when biopsied demonstrate interface
      dermatitis and those that do not demonstrate interface dermatitis. The skin
      lesions that are represented by the interface dermatitis include discoid lupus
      erythematosus, subacute cutaneous lupus erythematosus and acute cutaneous lupus
      erythematosus. Patients with these 'specific' manifestations have varying degrees
      of systemic involvement from rare systemic disease in patients with localized
      discoid lupus erythematosus to common and often severe involvement in patients
      with acute cutaneous lupus erythematosus. Patients who do not demonstrate
      interface dermatitis also may have systemic disease and in some instances the
      skin manifestations are linked to some of the more severe systemic
      manifestations. Many patients with cutaneous lesions characterized by the
      interface dermatitis can be controlled with 'standard' therapies including
      sunscreens, protective clothing and behavioural alteration, and topical
      corticosteroids with or without an oral antimalarial agent. This review presents
      a brief summary of each common cutaneous manifestation of lupus erythematosus,
      its relationship to systemic involvement and treatment issues to effectively deal
      with the lupus erythematosus patient who has skin disease.

PMID- 16405479
TI  - Defining patients with high-risk cutaneous squamous cell carcinoma.
AB  - SUMMARY Non-melanoma skin cancers occur at an epidemic rate in Australia. With an
      ageing population more Australians will develop these cancers and at an
      increasing rate. In the majority of cases, local treatment, usually excision, is
      highly curative. However, a subset of the population are diagnosed with a high
      risk cutaneous squamous cell carcinoma, defined as a patient having a higher risk
      of subclinical metastases to regional lymph nodes based on unfavourable primary
      lesion features and patient factors. Despite treatment, patients developing
      metastatic cutaneous squamous cell carcinoma experience mortality and morbidity
      usually as a consequence of uncontrolled metastatic nodal disease. It is
      therefore important that clinicians treating skin cancers have an understanding
      and awareness of these high-risk patients. The aim of this article is to discuss
      the features that define a high-risk patient and to present some of the issues
      pertinent to their treatment.

PMID- 16405480
TI  - Use of systemic glucocorticosteroids in pregnancy: be alert but not alarmed.
AB  - SUMMARY Concerns have been raised regarding the use of repeated courses of
      systemic glucocorticosteroids given to pregnant women with threatened premature
      labour to improve fetal lung maturity. Most worrying are animal studies showing
      detrimental effects on the developing brain, though human data to date are
      conflicting. Additional concerns relate to the fetal origins of adult diseases,
      particularly vascular diseases such as hypertension and atherosclerosis. It is
      currently recommended that obstetricians give only a single course of antenatal
      corticosteroids to pregnant women to enhance lung maturity instead of giving
      repeated doses, which was previously a common practice. Other clinicians
      including dermatologists, gastroenterologists and rheumatologists may have reason
      to provide systemic glucocorticosteroids to pregnant women. Although systemic
      glucocorticosteroids all cross the placenta to some degree, the extent to which
      they do so depends on the drug involved. The choice of systemic
      glucocorticosteroid for the pregnant women in light of this evolving literature
      is discussed.

PMID- 16405481
TI  - Quality of life in psoriasis improves after standardized administration of
      narrowband UVB phototherapy.
AB  - SUMMARY Psoriasis is a chronic fluctuating dermatosis with demonstrable impact on
      patients' quality of life. Our aim was to investigate if narrowband UVB
      phototherapy administered to psoriatic patients in a standardized manner leads to
      an improvement in patients' perceived quality of life. A total of 138 patients
      with psoriasis were recruited from referrals to the Skin and Cancer Foundation,
      Australia between January 1998 and September 2002. Patients had psoriasis
      inadequately controlled by topical therapies alone and no contraindications to
      the use of phototherapy. Patients completed a pre- and post-therapy questionnaire
      on quality of life parameters. The differences in mean and standard deviation of
      quality of life parameters were measured using a paired sample t-test based on
      pre- and post-phototherapy questionnaires. Ninety patients were included in the
      study. Forty-eight patients were excluded as they had not completed post
      phototherapy questionnaires. The course of narrowband UVB phototherapy was found
      to significantly improve quality of life in psoriasis patients (P <or= 0.005). We
      conclude that narrowband UVB phototherapy improves quality of life in patients
      with psoriasis.

PMID- 16405482
TI  - Skin prick testing to food allergens in breast-fed young infants with moderate to
      severe atopic dermatitis.
AB  - SUMMARY The role of food allergy in atopic dermatitis is controversial. This
      study presents results of skin prick tests to 31 different food allergens in a
      selected population of predominantly breast-fed young infants who had moderate to
      severe generalized atopic dermatitis. Of the 59 infants (22 female, mean age 26.5
      weeks) tested, 54 infants (91.5%) had positive responses to one or more foods, 53
      infants (90%) were positive to one or more of the five common food allergens (egg
      white, cow's milk, peanuts, wheat or soy) and 80% were positive to egg white,
      which was by far the most common positive test. A total of 37 infants had
      strongly positive responses to one or more foods, with 33 of these 37 having
      strongly positive responses to egg white. The significance of these responses is
      discussed. It is concluded that positive skin prick tests to foods, particularly
      to egg white, are very common in this selected population of breast-fed infants
      with moderate to severe atopic dermatitis.

PMID- 16405483
TI  - An open-label, pilot study examining the efficacy of curettage followed by
      imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma.
AB  - SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of
      primary superficial basal cell carcinoma has been established. This study
      investigated its efficacy following curettage (without electrodesiccation) for
      the treatment of primary nodular basal cell carcinoma on the trunk and limbs.
      Seventeen patients with a total of 34 lesions were enrolled. Curettage was used
      to de-bulk the lesion and confirm suitable histology. Lesions displaying more
      aggressive subtypes (such as micronodular or morpheoic components) were excluded.
      Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three
      months post treatment all lesions were excised, and 32 of 34 treated lesions
      (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients
      rated the cosmetic outcome of treatment as excellent or good. Curettage followed
      by imiquimod 5% cream is effective for the treatment of primary nodular basal
      cell carcinoma on the trunk and limbs, and most patients are pleased with the
      cosmetic outcome.

PMID- 16405484
TI  - Connective tissue panniculitis in a child with vitiligo and Hashimoto's
      thyroiditis.
AB  - SUMMARY A 9-year-old girl presented with a 6-month history of inflamed tender
      nodules in the pretibial area. These eventually healed leaving depressed areas of
      atrophy and loss of subcutaneous tissue. Histology showed a predominantly
      lymphocytic lobular panniculitis, consistent with connective tissue panniculitis.
      Investigations revealed an elevated thyroid stimulating hormone, elevated thyroid
      antiperoxidase antibody and a weakly positive antinuclear antibody (titre 1 in
      40). She was commenced on hydroxychloroquine 300 mg daily, which resulted in
      resolution of the panniculitis. She developed focal vitiligo on the thighs. This
      gradually improved with 0.1% mometasone furoate ointment. The hydroxychloroquine
      dose was tapered to 200 mg daily after 12 months, then to 100 mg daily after 18
      months therapy. Her thyroid autoantibody levels continued to rise and the
      hydroxychloroquine was increased again to 300 mg daily. She became borderline
      hypothyroid. Hashimoto's thyroiditis was diagnosed. Thyroxine was instituted with
      a resultant improvement in her thyroid blood tests. The lipoatrophy has not
      developed further during 2-year follow up.

PMID- 16405485
TI  - Squamous cell carcinoma of the hand masquerading as a cutaneous infection.
AB  - SUMMARY A 33-year-old male concreter presented with a small abscess on his right
      index finger following an injury at work. Histological examination of the lesion
      was consistent with chronic inflammation and Staphylococcus aureus, Streptococcus
      anginosus and Escherichia coli were isolated on cultures. The lesion was treated
      as a chronic fungal infection with bacterial superinfection. Seventeen months
      later, a bone scan showed periarticular involvement, and a diagnostic biopsy
      identified a well-differentiated squamous cell carcinoma. He underwent amputation
      of his index and middle fingers. After 4 years of follow up, there has been no
      evidence of recurrence at the primary site, but he has since developed two
      further primary squamous cell carcinomas. This case emphasizes the importance of
      considering malignancy when dealing with chronic infections of the hand.

PMID- 16405486
TI  - Pravastatin-induced lichenoid drug eruption.
AB  - SUMMARY A 64-year-old woman presented with diffuse and numerous pigmented macules
      on her face and upper back. Histopathological examination of a skin punch biopsy
      of the rash showed a lichenoid dermatitis. The most likely offending drug was
      pravastatin. Cessation of pravastatin resulted in gradual fading of the
      pigmentation. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have
      previously been reported to cause lichenoid drug eruptions.

PMID- 16405487
TI  - Epiluminescence dermatoscopy enhanced patient compliance and achieved treatment
      success in pseudofolliculitis barbae.
AB  - SUMMARY A patient presented with recalcitrant pseudofolliculitis barbae and
      hypertrophic scarring. The use of epiluminescence dermatoscopy rendered clear
      visualization of U-shaped ingrowing hairs corresponding to the sites of
      individual papules. Such real-time demonstration led to an attitude change and
      good compliance with medical advice against over shaving, resulting in a
      successful treatment outcome.

PMID- 16405488
TI  - Alopecia areata masquerading as frontal fibrosing alopecia.
AB  - SUMMARY Postmenopausal women with frontal recession may represent a diagnostic
      challenge, as frontal fibrosing alopecia and alopecia areata may be clinically
      difficult to distinguish. A 53-year-old postmenopausal woman presented with a
      progressive fronto-temporal marginal alopecia with sparing of her eyebrows. Scalp
      biopsy of the affected frontal hairline revealed peribulbar lymphocytic
      inflammation, but no evidence of lichenoid inflammation, perifollicular fibrosis
      or scarring. Whereas the pathology strongly favoured alopecia areata, the
      clinical features overlapped with frontal fibrosing alopecia, a variant of lichen
      planopilaris targeting the frontal scalp. This paper presents an atypical
      clinical presentation of alopecia areata, which may be mistaken for frontal
      fibrosing alopecia.

PMID- 16405489
TI  - Allergic contact dermatitis to thiourea in a neoprene knee brace.
AB  - SUMMARY An elderly woman developed an itchy, weeping, erythematous, papular
      eruption, confined to the skin under her neoprene knee brace. Allergic contact
      dermatitis to diethylthiourea and to her neoprene knee brace were diagnosed by
      positive patch test reactions. Allergic contact dermatitis from thioureas may be
      underdiagnosed, as they are not tested as part of the standard patch test series.
      Clinicians are encouraged to consider this diagnosis in patients with reactions
      to synthetic rubber, especially neoprene.

PMID- 16405490
TI  - Alar anaesthesia: A kinder method.
AB  - SUMMARY Local infiltration of anaesthetic in the ala of the nose is very
      uncomfortable for most patients. This is an area frequently operated on by
      dermatosurgeons under local anaesthesia as it is a common site for non-melanoma
      cutaneous malignancies. A simple method is described of providing more pleasant
      local anaesthesia for patients undergoing alar surgery by using nerve blocks
      prior to local infiltration.

PMID- 16405491
TI  - Incomplete biopsy of melanocytic lesions can impair the accuracy of pathological
      diagnosis.

PMID- 16405492
TI  - Partial biopsy of pigmented lesions: proceed with caution.

PMID- 16405496
TI  - Glia re-sealed particles freshly prepared from adult rat brain are competent for
      exocytotic release of glutamate.
AB  - Glial subcellular re-sealed particles (referred to as gliosomes here) were
      purified from rat cerebral cortex and investigated for their ability to release
      glutamate. Confocal microscopy showed that the glia-specific proteins glial
      fibrillary acidic protein (GFAP) and S-100, but not the neuronal proteins 95-kDa
      postsynaptic density protein (PSD-95), microtubule-associated protein 2 (MAP-2)
      and beta-tubulin III, were enriched in purified gliosomes. Furthermore, gliosomes
      exhibited labelling neither for integrin-alphaM nor for myelin basic protein,
      which are specific for microglia and oligodendrocytes respectively. The Ca2+
      ionophore ionomycin (0.1-5 microm) efficiently stimulated the release of tritium
      from gliosomes pre-labelled with [3H]d-aspartate and of endogenous glutamate in a
      Ca(2+)-dependent and bafilomycin A1-sensitive manner, suggesting the involvement
      of an exocytotic process. Accordingly, ionomycin was found to induce a Ca(2+)
      dependent increase in the vesicular fusion rate, when exocytosis was monitored
      with acridine orange. ATP stimulated [3H]d-aspartate release in a concentration-
      (0.1-3 mm) and Ca(2+)-dependent manner. The gliosomal fraction contained proteins
      of the exocytotic machinery [syntaxin-1, vesicular-associated membrane protein
      type 2 (VAMP-2), 23-kDa synaptosome-associated protein (SNAP-23) and 25-kDa
      synaptosome-associated protein (SNAP-25)] co-existing with GFAP immunoreactivity.
      Moreover, GFAP or VAMP-2 co-expressed with the vesicular glutamate transporter
      type 1. Consistent with ultrastructural analysis, several approximately 30-nm non
      clustered vesicles were present in the gliosome cytoplasm. It is concluded that
      gliosomes purified from adult brain contain glutamate-accumulating vesicles and
      can release the amino acid by a process resembling neuronal exocytosis.

PMID- 16405497
TI  - Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease.
AB  - Information processing and storing by brain networks requires a highly
      coordinated operation of multiple neuronal groups. The function of septal neurons
      is to modulate the activity of archicortical (e.g. hippocampal) and neocortical
      circuits. This modulation is necessary for the development and normal occurrence
      of rhythmical cortical activities that control the processing of sensory
      information and memory functions. Damage or degeneration of septal neurons
      results in abnormal information processing in cortical circuits and consequent
      brain dysfunction. Septal neurons not only provide the optimal levels of
      excitatory background to cortical structures, but they may also inhibit the
      occurrence of abnormal excitability states.

PMID- 16405498
TI  - Calpain is activated in degenerating photoreceptors in the rd1 mouse.
AB  - The retinal degeneration (rd)1 mouse displays an inherited retinal degeneration
      and therefore allows studies of the molecular mechanisms behind the blinding
      disease retinitis pigmentosa. Activation of the calcium-dependent protease
      calpain has been suggested to play an important role in cell death in various
      tissues, but little is known about the expression and activity of calpain during
      inherited retinal degeneration. Using microarray techniques, transcript levels of
      cyclic AMP response element-binding protein (CREB)-1, calpastatin and of various
      calpain genes were analysed in the rd1 mouse compared with its wild-type control.
      Expression of distinct calpain isoforms and calpastatin was investigated using
      immunofluorescence and immunoblotting. Gene transcription and protein expression
      levels were compared with calpain activity using an enzymatic assay that allowed
      monitoring of calpain activity at the cellular level. We found that CREB-1 and
      calpastatin expression was reduced in rd1 retinas, whereas calpain activity was
      substantially increased in rd1 photoreceptors. Calpain activity peaked at
      postnatal day 13, together with rd1 photoreceptor cell death. Calpain-specific
      inhibitors decreased calpain activity in situ. These results indicate that
      activation of calpains correlates with rd1 photoreceptor cell death, which raises
      the possibility of using calpain inhibitors to prevent or delay photoreceptor
      degeneration.

PMID- 16405499
TI  - The inflammatory transcriptome of reactive murine astrocytes and implications for
      their innate immune function.
AB  - Upon injury, astrocytes assume an activated state associated with the release of
      inflammatory mediators. To model this, we stimulated murine primary astrocytes
      with a complete inflammatory cytokine mix consisting of TNF-alpha, IL-1beta and
      IFN-gamma. We analysed the transcriptional response of 480 genes at 4 and 16 h
      after stimulation on a chip designed to give a representative overview over the
      inflammation-relevant part of the transcriptome of macrophage-like cells. The
      list of the 182 genes found to be significantly regulated in astrocytes revealed
      an intriguing co-ordinate regulation of genes linked to the biological processes
      of antiviral/antimicrobial defence, antigen presentation and facilitation of
      leucocyte invasion. The latter group was characterized by very high up
      regulations of chemokine genes. We also identified regulations of a thymidylate
      kinase and an interferon-regulated protein with a tetratricopeptide motive, both
      up to now only known from macrophages. The transcriptional regulations were
      confirmed on the protein level by a proteomic analysis. These findings taken
      together suggest that activated astrocytes in brain behave similarly in many
      respects to inflamed macrophages in the periphery.

PMID- 16405500
TI  - Interaction of huntingtin fragments with brain membranes--clues to early
      dysfunction in Huntington's disease.
AB  - Abstract Huntingtin is a large, multi-domain protein of unknown function in the
      brain. An abnormally elongated polyglutamine stretch in its N-terminus causes
      Huntington's disease (HD), a progressive neurodegenerative disorder. Huntingtin
      has been proposed to play a functional role in membrane trafficking via proteins
      involved in endo- and exocytosis. Here, we supply evidence for a direct
      association between huntingtin and membranes. In the brains of R6/2 mice with HD
      pathology, a 64 kDa N-terminal huntingtin fragment accumulated in postsynaptic
      membranes during the pre-symptomatic period of 4-8 weeks of age. In addition, an
      oligomeric fragment of approximately 200 kDa was detected at 8 weeks of age.
      Simultaneous progressive changes in distribution of amphiphysin, synaptojanin,
      and subunits of NMDA- and AMPA-receptors provide a strong indication of
      dysfunctional synaptic trafficking. Composition of the major phospholipids in the
      synaptic membranes was unaffected. In vitro, large unilamellar vesicles of brain
      lipids readily associated with soluble N-terminal huntingtin exon 1 fragments and
      stimulated fibrillogenesis of mutant huntingtin aggregates. Moreover, interaction
      of both mutant and wild-type huntingtin exon 1 fragments with brain lipids caused
      bilayer perturbation, mediated through a proline-rich region adjacent to the
      polyglutamines. This suggests that lipid interactions in vivo could influence
      misfolding of huntingtin and may play an early role in HD pathogenesis.

PMID- 16405501
TI  - Sites in TM2 and 3 are critical for alcohol-induced conformational changes in
      GABA receptors.
AB  - Abstract gamma-Aminobutyric acid type A (GABA(A)) receptors are molecular targets
      for alcohols. Previous work suggests that S270 and A291 residues in the
      transmembrane (TM) 2 and 3 domains of the GABA(A) receptor alpha subunit are
      components of an alcohol-binding pocket, and S270I and A291W mutants abolished
      ethanol potentiation. Our results showed that A295C and F296C residues in the TM3
      of the GABA(A) receptor alpha1 subunit are accessible to
      hexylmethanethiosulfonate (HMTS) in the alcohol-bound state, but not in the
      resting state. Thus, the A295C and F296C sites become water-accessible as a
      result of alcohol-induced conformational changes. If S270 or A291 residues are
      sites of alcohol binding, then S270I or A291W mutations should prevent alcohol
      induced conformational movements within the TM3 domain. To investigate this
      question, the accessibility of HMTS reagent to double mutants (A291W/A295C,
      A291W/F296C, S270I/A295C or S270I/F296C) in the presence of ethanol or hexanol
      was tested. The A291W or S270I mutations markedly reduced the accessibility of
      HMTS to all the double mutants in the ethanol-bound state, and to S270I/F296C,
      A291W/A295C and A291W/F296C double mutants in the hexanol-bound state, suggesting
      that the A291 or S270 residues are critical sites for alcohol binding and alcohol
      induced conformational changes.

PMID- 16405502
TI  - Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive
      impairment.
AB  - Increasing evidence suggests that oxidative damage is associated with normal
      aging and several neurodegenerative diseases. Mild cognitive impairment (MCI),
      the phase between normal aging and early dementia, is a common problem in the
      elderly with many subjects going on to develop Alzheimer's disease (AD). Although
      increased DNA oxidation is observed in the AD brain, it is unclear when the
      oxidative damage begins. To determine if DNA oxidation occurs in the brain of
      subjects with MCI, we quantified multiple oxidized bases in nuclear and
      mitochondrial DNA isolated from frontal, parietal and temporal lobes and
      cerebellum of short post-mortem interval autopsies of eight amnestic patients
      with MCI and six age-matched control subjects using gas chromatography/mass
      spectrometry with selective ion monitoring. We found statistically significant
      elevations (p < 0.05) of 8-hydroxyguanine, a widely studied biomarker of DNA
      damage, in MCI nuclear DNA from frontal and temporal lobe and in mitochondrial
      DNA from the temporal lobe compared with age-matched control subjects. Levels of
      8-hydroxyadenine and 4,6-diamino-5-formamidopyrimidine were significantly
      elevated in nuclear DNA from all three neocortical regions in MCI. Statistically
      significant elevations of 4,6-diamino-5-formamidopyrimidine were also observed in
      mitochondrial DNA of MCI temporal, frontal and parietal lobes. These results
      suggest that oxidative damage to nuclear and mitochondrial DNA occurs in the
      earliest detectable phase of AD and may play a meaningful role in the
      pathogenesis of this disease.

PMID- 16405503
TI  - Resting and arecoline-stimulated brain metabolism and signaling involving
      arachidonic acid are altered in the cyclooxygenase-2 knockout mouse.
AB  - Abstract Studies were performed to determine if cyclooxygenase (COX)-2 regulates
      muscarinic receptor-initiated signaling involving brain phospholipase A2 (PLA2)
      activation and arachidonic acid (AA; 20 : 4n-6) release. AA incorporation
      coefficients, k* (brain [1-14C]AA radioactivity/integrated plasma radioactivity),
      representing this signaling, were measured following the intravenous injection of
      [1-14C]AA using quantitative autoradiography, in each of 81 brain regions in
      unanesthetized COX-2 knockout (COX-2(-/-)) and wild-type (COX-2(+/+)) mice. Mice
      were administered arecoline (30 mg/kg i.p.), a non-specific muscarinic receptor
      agonist, or saline i.p. (baseline control). At baseline, COX-2(-/-) compared with
      COX-2(+/+) mice had widespread and significant elevations of k*. Arecoline
      increased k* significantly in COX-2(+/+) mice compared with saline controls in 72
      of 81 brain regions, but had no significant effect on k* in any region in COX-2(
      /-) mice. These findings, when related to net incorporation rates of AA from
      brain into plasma, demonstrate enhanced baseline brain metabolic loss of AA in
      COX-2(-/-) compared with COX-2(+/+) mice, and an absence of a normal k* response
      to muscarinic receptor activation. This response likely reflects selective COX-2
      mediated conversion of PLA2-released AA to prostanoids.

PMID- 16405504
TI  - In vivo post-transcriptional regulation of GAP-43 mRNA by overexpression of the
      RNA-binding protein HuD.
AB  - HuD is a neuronal-specific RNA-binding protein that binds to and stabilizes the
      mRNAs of growth-associated protein-43 (GAP-43) and other neuronal proteins. HuD
      expression increases during brain development, nerve regeneration, and learning
      and memory, suggesting that this protein is important for controlling gene
      expression during developmental and adult plasticity. To examine the function of
      HuD in vivo, we generated transgenic mice overexpressing human HuD under the
      control of the calcium-calmodulin-dependent protein kinase IIalpha promoter. The
      transgene was expressed at high levels throughout the forebrain, including the
      hippocampal formation, amygdala and cerebral cortex. Using quantitative in situ
      hybridization, we found that HuD overexpression led to selective increases in GAP
      43 mRNA in hippocampal dentate granule cells and neurons in the lateral amygdala
      and layer V of the neorcortex. In contrast, GAP-43 pre-mRNA levels were unchanged
      or decreased in the same neuronal populations. Comparison of the levels of mature
      GAP-43 mRNA and pre-mRNA in the same neurons of transgenic mice suggested that
      HuD increased the stability of the transcript. Confirming this, mRNA decay assays
      revealed that the GAP-43 mRNA was more stable in brain extracts from HuD
      transgenic mice than non-transgenic littermates. In conclusion, our results
      demonstrate that HuD overexpression is sufficient to increase GAP-43 mRNA
      stability in vivo.

PMID- 16405505
TI  - Mouse tryptophan hydroxylase isoform 2 and the role of proline 447 in enzyme
      function.
AB  - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of the
      neurotransmitter serotonin (5-HT). Once thought to be a single gene product, TPH
      is now known to exist in two isoforms. Isoform 1 (TPH1) is found in the pineal
      gland and gut, and isoform 2 (TPH2) is selectively expressed in brain. A single
      nucleotide polymorphism in TPH2 results in a proline-to-arginine mutation at
      residue 447 and substantially lowers catalytic activity. In view of the
      importance of TPH in determining brain 5-HT function, we cloned TPH2 and produced
      the P447R mutant to assess the importance of this proline in enzyme function.
      Catalytically active TPH2 and the P447R mutant were expressed at the predicted
      subunit molecular mass of 56 kDa. The P447R mutant expressed less than 50% of the
      activity of TPH2. Mutation of this conserved proline in TPH1 (P403R) also
      resulted in an enzyme with significantly lower activity than the wild-type
      enzyme. The P447R mutant had a V(max) 50% lower than that of TPH2. The P447R
      mutation did not alter the oligomeric assembly of the protein, nor change its
      responsiveness to cysteine modification. The P447R mutation did not alter enzyme
      substrate specificity or stability, but conferred slightly enhanced sensitivity
      to inhibition by dopamine and diminished sensitivity to iron in catalysis. The
      conserved proline in TPH (residue 447 in TPH2 and 403 in TPH1) plays an important
      role in enzyme function by regulating V(max) of the catalytic reaction.

PMID- 16405507
TI  - The 5-HT(1A) receptor agonist 8-OH-DPAT prevents prefrontocortical glutamate and
      serotonin release in response to blockade of cortical NMDA receptors.
AB  - We studied the role of 5-HT(1A) receptors in controlling the release of glutamate
      (GLU) in the medial prefrontal cortex (mPFC) of conscious rats with the in vivo
      microdialysis technique. The effect of the 5-HT(1A) receptor agonist 8-hydroxy-2
      (di-n-propylamino)tetralin infused in the prefrontal cortex was examined under
      basal conditions and on the rise of extracellular GLU (+106%) induced by co
      infusion of the competitive N-methyl-d-aspartate receptor antagonist 3-[(R)-2
      carboxypiperazin-4yl]-propyl-1-phosphonic acid (CPP). 8-OH-DPAT (0.3 and 3
      microm) had no effect on basal extracellular GLU, but the higher concentration
      completely abolished the rise of extracellular GLU induced by CPP. CPP also
      increased extracellular serotonin (5-HT) in the mPFC (+50%) and this effect was
      antagonized by 3 microm 8-OH-DPAT which, by itself, had no effect on basal 5-HT
      release. The effects of 8-OH-DPAT on extracellular GLU and 5-HT were reversed by
      the 5-HT(1A) receptor antagonist WAY100 635 (100 microm), indicating a selective
      involvement of 5-HT(1A) receptors. WAY100 635 had no effect by itself. These
      results show that the stimulation of cortical 5-HT(1A) receptors prevents the CPP
      evoked rise of extracellular GLU and 5-HT and suggest that these effects may
      contribute to the ability of intracortical 8-OH-DPAT to counteract cognitive
      deficits caused by the blockade of NMDA receptors.

PMID- 16405506
TI  - 2-Deoxyglucose and NMDA inhibit protein synthesis in neurons and regulate
      phosphorylation of elongation factor-2 by distinct mechanisms.
AB  - Cerebral ischaemia is associated with brain damage and inhibition of neuronal
      protein synthesis. A deficit in neuronal metabolism and altered excitatory amino
      acid release may both contribute to those phenomena. In the present study, we
      demonstrate that both NMDA and metabolic impairment by 2-deoxyglucose or
      inhibitors of mitochondrial respiration inhibit protein synthesis in cortical
      neurons through the phosphorylation of eukaryotic elongation factor (eEF-2),
      without any change in phosphorylation of initiation factor eIF-2alpha. eEF-2
      kinase may be activated both by Ca(2+)-independent AMP kinase or by an increase
      in cytosolic Ca2+. Although NMDA decreases ATP levels in neurons, only the
      effects of 2-deoxyglucose on protein synthesis and phosphorylation of elongation
      factor eEF-2 were reversed by Na(+) pyruvate. Protein synthesis inhibition by 2
      deoxyglucose was not as a result of a secondary release of glutamate from
      cortical neurons as it was not prevented by the NMDA receptor antagonist 5-methyl
      10,11-dihydro-5H-dibenzo-(a,d)-cyclohepten-5,10-imine hydrogen maleate (MK 801),
      nor to an increase in cytosolic-free Ca2+. Conversely, 2-deoxyglucose likely
      activates eEF-2 kinase through a process involving phosphorylation by AMP kinase.
      In conclusion, we provide evidence that protein synthesis can be inhibited by
      NMDA and metabolic deprivation by two distinct mechanisms involving,
      respectively, Ca(2+)-dependent and Ca(2+)-independent eEF-2 phosphorylation.

PMID- 16405508
TI  - Interleukin-1 beta-induced expression of the prostaglandin E-receptor subtype EP3
      in U373 astrocytoma cells depends on protein kinase C and nuclear factor-kappaB.
AB  - Both interleukin-1beta (IL-1beta) and prostaglandins (PGs) are important
      mediators of physiological and pathophysiological processes in the brain. PGE2
      exerts its effects by binding to four different types of PGE2 receptors named EP1
      EP4. EP3 has found to be expressed in neurons, whereas expression of EP3 in glial
      cells has not been reported in the brain yet. Here we describe IL-1beta-induced
      EP3 receptor expression in human astrocytoma cells, primary astrocytes of rat and
      human origin and in rat brain. Using western blot, we found a marked up
      regulation of EP3 receptor synthesis in human and rat primary glial cells.
      Intracerebroventricular administration of IL-1beta stimulated EP3 receptor
      synthesis in rat hippocampus. The analysis of involved signal transduction
      pathways by pathway-specific inhibitors revealed an essential role of protein
      kinase C and nuclear factor-kappaB in astrocytic IL-1beta-induced EP3 synthesis.
      Our data suggest that PGE2 signaling in the brain may be altered after IL-1beta
      release due to up-regulation of EP3 receptors. This might play an important role
      in acute and chronic conditions such as cerebral ischemia, traumatic brain
      injury, HIV-encephalitis, Alzheimer's disease and prion diseases in which a
      marked up-regulation of IL-1beta is followed by a prolonged increase of PGE2
      levels in the brain.

PMID- 16405509
TI  - Internalization and desensitization of a green fluorescent protein-tagged P2Y
      nucleotide receptor are differently controlled by inhibition of calmodulin
      dependent protein kinase II.
AB  - De- and re-sensitization and trafficking of P2Y nucleotide receptors modulate
      physiological responses of these receptors. Here, we used the rat brain P2Y1
      receptor tagged with green fluorescent protein (P2Y1-GFP receptor) expressed in
      HEK293 human embryonic kidney cells. Ca2+ release was used as a functional test
      to investigate ATP-induced receptor de- and re-sensitization. By confocal laser
      scanning microscopy (CLSM), endocytosis of P2Y1-GFP receptor was visualized in
      live cells. Stimulation of the cells with ATP induced complete receptor
      endocytosis within 30 min and appearance of the P2Y1 receptor in small vesicles.
      Removal of the agonist resulted in reappearance of the receptor after 60 min on
      the plasma membrane. Exposure of the cells to KN-62 and KN-93, inhibitors of the
      calmodulin dependent protein kinase II (CaMKII), prevented receptor
      internalization upon stimulation with ATP. However, the receptor which was still
      present on the plasma membrane was desensitized, seen by decreased Ca2+ response.
      The decreased Ca2+ response after 30-min exposure to ATP can be attributed to
      desensitization and is not as a result of depletion of internal stores, as the
      cells exposed to ATP for 30 min exhibited a normal Ca2+ response upon stimulation
      with thrombin. However, okadaic acid, an inhibitor of protein phosphatase 2A
      (PP2A), did not affect ATP-induced P2Y1 receptor endocytosis, but delayed the
      reappearance of the P2Y1 receptor on the plasma membrane after ATP withdrawal.
      Consistently, in okadaic acid-treated cells the ATP-induced Ca2+ response
      observed after the 30-min exposure to ATP recovered only partially. Thus, CaMKII
      seems to be involved in P2Y1 receptor internalization, but not desensitization,
      whereas protein phosphatase 2A might play a role in recycling of the receptor
      back to the plasma membrane.

PMID- 16405510
TI  - Selective deficits in the expression of striatal-enriched mRNAs in Huntington's
      disease.
AB  - We have identified and cataloged 54 genes that exhibit predominant expression in
      the striatum. Our hypothesis is that such mRNA molecules are likely to encode
      proteins that are preferentially associated with particular physiological
      processes intrinsic to striatal neurons, and therefore might contribute to the
      regional specificity of neurodegeneration observed in striatal disorders such as
      Huntington's disease (HD). Expression of these genes was measured simultaneously
      in the striatum of HD R6/1 transgenic mice using Affymetrix oligonucleotide
      arrays. We found a decrease in expression of 81% of striatum-enriched genes in HD
      transgenic mice. Changes in expression of genes associated with G-protein
      signaling and calcium homeostasis were highlighted. The most striking decrement
      was observed for a newly identified subunit of the sodium channel, beta 4, with
      dramatic decreases in expression beginning at 8 weeks of age. A subset of
      striatal genes was tested by real-time PCR in caudate samples from human HD
      patients. Similar alterations in expression were observed in human HD and the
      R6/1 model for the striatal genes tested. Expression of 15 of the striatum
      enriched genes was measured in 6-hydroxydopamine-lesioned rats to determine their
      dependence on dopamine innervation. No changes in expression were observed for
      any of these genes. These findings demonstrate that mutant huntingtin protein
      causes selective deficits in the expression of mRNAs responsible for striatum
      specific physiology and these may contribute to the regional specificity of
      degeneration observed in HD.

PMID- 16405511
TI  - Neprilysin participates in skeletal muscle regeneration and is accumulated in
      abnormal muscle fibres of inclusion body myositis.
AB  - Neprilysin (NEP, EP24.11), a metallopeptidase originally shown to modulate
      signalling events by degrading small regulatory peptides, is also an amyloid-beta
      (Abeta) degrading enzyme. We investigated a possible role of NEP in inclusion
      body myositis (IBM) and other acquired and hereditary muscle disorders and found
      that in all myopathies NEP expression was directly associated with the degree of
      muscle fibre regeneration. In IBM muscle, NEP protein was also strongly
      accumulated in Abeta-bearing abnormal fibres. In vitro, during the experimental
      differentiation of myoblasts, NEP protein expression was regulated at the post
      transcriptional level with a rapid increase in the early stage of myoblast
      differentiation followed by a gradual reduction thereafter, coincident with the
      progression of the myogenic programme. Treatment of differentiating muscle cells
      with the NEP inhibitor dl-3-mercapto-2-benzylpropanoylglycine resulted in
      impaired differentiation that was mainly associated with an abnormal regulation
      of Akt activation. Therefore, NEP may play an important role during muscle cell
      differentiation, possibly through the regulation, either directly or indirectly,
      of the insulin-like growth factor I-driven myogenic programme. In IBM muscle
      increased NEP may be instrumental in (i) reducing the Abeta accumulation in
      vulnerable fibres and (ii) promoting a repair/regenerative attempt of muscle
      fibres possibly through the modulation of insulin-like growth factor I-dependent
      pathways.

PMID- 16405512
TI  - O6-methylguanine DNA methyltransferase and p53 status predict temozolomide
      sensitivity in human malignant glioma cells.
AB  - Temozolomide (TMZ) is a methylating agent which prolongs survival when
      administered during and after radiotherapy in the first-line treatment of
      glioblastoma and which also has significant activity in recurrent disease. O6
      methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme attributed a
      role in cancer cell resistance to O6-alkylating agent-based chemotherapy. Using a
      panel of 12 human glioma cell lines, we here defined the sensitivity to TMZ in
      acute cytotoxicity and clonogenic survival assays in relation to MGMT, mismatch
      repair and p53 status and its modulation by dexamethasone, irradiation and BCL
      X(L). We found that the levels of MGMT expression were a major predictor of TMZ
      sensitivity in human glioma cells. MGMT activity and clonogenic survival after
      TMZ exposure are highly correlated (p < 0.0001, r2 = 0.92). In contrast,
      clonogenic survival after TMZ exposure does not correlate with the expression
      levels of the mismatch repair proteins mutS homologue 2, mutS homologue 6 or post
      meiotic segregation increased 2. The MGMT inhibitor O6-benzylguanine sensitizes
      MGMT-positive glioma cells to TMZ whereas MGMT gene transfer into MGMT-negative
      cells confers protection. The antiapoptotic BCL-X(L) protein attenuates TMZ
      cytotoxicity in MGMT-negative LNT-229 but not in MGMT-positive LN-18 cells.
      Neither ionizing radiation (4 Gy) nor clinically relevant concentrations of
      dexamethasone modulate MGMT activity or TMZ sensitivity. Abrogation of p53 wild
      type function strongly attenuates TMZ cytotoxicity. Conversely, p53 mimetic
      agents designed to stabilize the wild-type conformation of p53 sensitize glioma
      cells for TMZ cytotoxicity. Collectively, these results suggest that the
      determination of MGMT expression and p53 status will help to identify glioma
      patients who will or will not respond to TMZ.

PMID- 16405513
TI  - Presenilin clinical mutations can affect gamma-secretase activity by different
      mechanisms.
AB  - Mutations in human presenilin (PS) genes cause aggressive forms of familial
      Alzheimer's disease. Presenilins are polytopic proteins that harbour the
      catalytic site of the gamma-secretase complex and cleave many type I
      transmembrane proteins including beta-amyloid precursor protein (APP), Notch and
      syndecan 3. Contradictory results have been published concerning whether PS
      mutations cause 'abnormal' gain or (partial) loss of function of gamma-secretase.
      To avoid the possibility that wild-type PS confounds the interpretation of the
      results, we used presenilin-deficient cells to analyse the effects of different
      clinical mutations on APP, Notch, syndecan 3 and N-cadherin substrate processing,
      and on gamma-secretase complex formation. A loss in APP and Notch substrate
      processing at epsilon and S3 cleavage sites was observed with all presenilin
      mutants, whereas APP processing at the gamma site was affected in variable ways.
      PS1-Delta9 and PS1-L166P mutations caused a reduction in beta-amyloid peptide
      Abeta40 production whereas PS1-G384A mutant significantly increased Abeta42.
      Interestingly PS2, a close homologue of PS1, appeared to be a less efficient
      producer of Abeta than PS1. Finally, subtle differences in gamma-secretase
      complex assembly were observed. Overall, our results indicate that the different
      mutations in PS affect gamma-secretase structure or function in multiple ways.

PMID- 16405514
TI  - Minocycline attenuates microglial activation but fails to mitigate striatal
      dopaminergic neurotoxicity: role of tumor necrosis factor-alpha.
AB  - Activated microglia are implicated in the pathogenesis of disease-, trauma- and
      toxicant-induced damage to the CNS, and strategies to modulate microglial
      activation are gaining impetus. A novel action of the tetracycline derivative
      minocycline is the ability to inhibit inflammation and free radical formation,
      factors that influence microglial activation. Minocycline is therefore being
      tested as a neuroprotective agent to alleviate CNS damage, although findings so
      far have yielded mixed results. Here, we showed that administration of a single
      low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or
      methamphetamine (METH), a paradigm that causes selective degeneration of striatal
      dopaminergic nerve terminals without affecting the cell body in substantia nigra,
      increased the expression of mRNAs encoding microglia-associated factors F4/80,
      interleukin (IL)-1alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1, CCL2)
      and tumor necrosis factor (TNF)-alpha. Minocycline treatment attenuated MPTP- or
      METH-mediated microglial activation, but failed to afford neuroprotection. Lack
      of neuroprotection was shown to be due to the inability of minocycline to abolish
      the induction of TNF-alpha and its receptors, thereby failing to modulate TNF
      signaling. Thus, TNF-alpha appeared to be an obligatory component of dopaminergic
      neurotoxicity. To address this possibility, we examined the effects of MPTP or
      METH in mice lacking genes encoding IL-6, CCL2 or TNF receptor (TNFR)1/2.
      Deficiency of either IL-6 or CCL2 did not alter MPTP neurotoxicity. However,
      deficiency of both TNFRs protected against the dopaminergic neurotoxicity of
      MPTP. Taken together, our findings suggest that attenuation of microglial
      activation is insufficient to modulate neurotoxicity as transient activation of
      microglia may suffice to initiate neurodegeneration. These findings support the
      hypothesis that TNF-alpha may play a role in the selective vulnerability of the
      nigrostriatal pathway associated with dopaminergic neurotoxicity and perhaps
      Parkinson's disease.

PMID- 16405515
TI  - Limited regulation of somatodendritic dopamine release by voltage-sensitive Ca
      channels contrasted with strong regulation of axonal dopamine release.
AB  - The mechanism underlying somatodendritic release of dopamine (DA) appears to
      differ from that of axon-terminal release. Specifically, somatodendritic DA
      release in the substantia nigra pars compacta (SNc) persists in low extracellular
      Ca2+ concentrations that are insufficient to support axonal release in striatum,
      suggesting that limited Ca2+ entry is necessary to trigger somatodendritic
      release. Here, we compared the role of voltage-dependent Ca2+ channels in
      mediating DA release in striatum versus SNc using specific blockers of N-, P/Q-,
      T-, R- and L-type Ca2+ channels individually and in combination. Release of DA
      evoked by a single stimulus pulse in the dorsal striatum and SNc of guinea-pig
      brain slices was monitored in real time using carbon-fiber microelectrodes with
      fast-scan cyclic voltammetry. Single-pulse evoked DA release was shown to be
      independent of regulation by concurrently released glutamate or GABA acting at
      ionotropic receptors in both regions. Under these conditions, striatal DA release
      was completely prevented by an N-type channel blocker, omega-conotoxin GVIA (100
      nm), and was decreased by 75% by the P/Q-type channel blocker omega-agatoxin IVA
      (200 nm). Blockade of T-type channels with Ni2+ (100 microm) or R-type channels
      with SNX-482 (100 nm) decreased axonal release in striatum by 25%, whereas
      inhibition of L-type channels with nifedipine (20 microm) had no effect. By
      contrast, none of these Ca2+-channel blockers altered the amplitude of
      somatodendritic DA release in the SNc. Even a cocktail of all blockers tested did
      not alter release-signal amplitude in the SNc, although the duration of the
      release response was curtailed. The limited involvement of voltage-dependent Ca2+
      channels in somatodendritic DA release provides further evidence that minimal
      Ca2+ entry is required to trigger the release process, compared with that
      required for axon-terminal release.

PMID- 16405517
TI  - Elevation of circulating endothelial microparticles in patients with chronic
      renal failure.
AB  - BACKGROUND: Chronic renal failure patients are at high risk of cardiovascular
      events and display endothelial dysfunction, a critical element in the
      pathogenesis of atherosclerosis. Upon activation, the endothelium sheds
      microparticles, considered as markers of endothelial dysfunction that also behave
      as vectors of bioactive molecules. AIM: To measure plasma levels of endothelial
      microparticles (EMPs) in chronic renal failure patients (CRF), either undialyzed
      or hemodialyzed (HD), and to investigate the ability of uremic toxins to induce
      EMP release in vitro. METHODS: Circulating EMPs were numerated by flow cytometry,
      after staining of platelet-free plasma with phycoerythrin (PE)-conjugated anti
      CD144 (CD144+ EMP) or anti-CD146 (CD146+ EMP) monoclonal antibodies. Platelet MP
      (CD41+ PMP), leukocyte MP (CD45+ leukocyte microparticles (LMP)), and annexin-V+
      MPs were also counted. In parallel, MPs were counted in supernatant of human
      umbilical vein endothelial cells incubated with uremic toxins [oxalate, indoxyl
      sulfate, p-cresol, and homocysteine (Hcy)], at concentrations found in patients.
      RESULTS AND CONCLUSIONS: CD144+ EMP and CD146+ EMP levels were significantly
      higher in CRF and HD patients than in healthy subjects. Furthermore, annexin-V+
      MPs were elevated in both groups of uremic patients, and CD41+ PMP and CD45+ LMP
      were increased in CRF and HD patients, respectively. In vitro, p-cresol and
      indoxyl sulfate significantly increased both CD146+ and annexin-V+ EMP release.
      Increased levels of circulating EMP in CRF and HD patients represent a new marker
      of endothelial dysfunction in uremia. The ability of p-cresol and indoxyl sulfate
      to increase EMP release in vitro suggests that specific uremic factors may be
      involved in EMP elevation in patients.

PMID- 16405518
TI  - Diagnosis of deep vein thrombosis and pulmonary embolism in pregnancy: a
      systematic review.
AB  - INTRODUCTION: Diagnosing deep vein thrombosis (DVT) and pulmonary embolism (PE)
      in pregnancy is challenging. Many of the common diagnostic tests, including
      compression ultrasonography (CUS), ventilation-perfusion scintigraphy (VQ scan)
      and helical computed tomography (hCT) that have been extensively investigated in
      non-pregnant patients, have not been appropriately validated in pregnancy.
      Extrapolating results of diagnostic studies of DVT and PE in non-pregnant
      patients to those who are pregnant may not be correct because during pregnancy,
      physiologic and anatomic changes may affect diagnostic test results, presentation
      and natural history of VTE. METHODS: We performed a systematic analysis of
      published studies addressing accurate diagnostic testing for DVT and PE in
      pregnancy to determine the accuracy of these tests in pregnancy. RESULTS: Our
      initial search yielded 530 articles of which four remained for inclusion, three
      studies investigating diagnostic testing in patients with a clinical suspicion of
      DVT or PE and one study in patients with a clinical suspicion of PE. CONCLUSIONS:
      From our systematic analysis of published studies investigating diagnostic
      testing for a clinical suspicion of DVT in pregnancy we conclude that; (i) two
      studies support withholding anticoagulant therapy in pregnant women with a
      clinical suspicion of DVT and normal results on serial IPG (impedance
      plethysmography), however, IPG is no longer used; (ii) one study demonstrated
      that a normal CUS at presentation combined with a normal D-dimer test or an
      abnormal D-dimer test combined with normal serial CUS appears promising for
      safely excluding DVT in pregnant patients, but too few patients were included in
      this pilot-study to draw firm conclusions; and (iii) one study investigated
      pregnant patients with a clinical suspicion of PE and this study concluded that
      in patients with normal or non-diagnostic VQ scans, withholding anticoagulant
      therapy might be safe, but this needs confirmation in larger studies.
      Recommendations on diagnostic testing of pregnant patients with a clinically
      suspected DVT or PE are provided.

PMID- 16405519
TI  - Variable therapeutic effectiveness of clopidogrel in acute coronary syndromes.

PMID- 16405520
TI  - Increased metastatic potential of tumor cells in von Willebrand factor-deficient
      mice.
AB  - BACKGROUND: The key role played by von Willebrand factor (VWF) in platelet
      adhesion suggests a potential implication in various pathologies, where this
      process is involved. In cancer metastasis development, tumor cells interact with
      platelets and the vessel wall to extravasate from the circulation. As a potential
      mediator of platelet-tumor cell interactions, VWF could influence this early step
      of tumor spread and therefore play a role in cancer metastasis. OBJECTIVES: To
      investigate whether VWF is involved in metastasis development. METHODS: In a
      first step, we characterized the interaction between murine melanoma cells B16
      BL6 and VWF in vitro. In a second step, an experimental metastasis model was used
      to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and
      VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma
      cells. RESULTS: In vitro adhesion assays revealed that VWF is able to promote a
      dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In
      the experimental metastasis model, we found a significant increase in the number
      of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a
      phenotype that could be corrected by restoring VWF plasma levels. We also showed
      that increased survival of the tumor cells in the lungs during the first 24 h in
      the absence of VWF was the cause of this increased metastasis. CONCLUSION: These
      findings suggest that VWF plays a protective role against tumor cell
      dissemination in vivo. Underlying mechanisms remain to be investigated.

PMID- 16405521
TI  - Gain- and loss-of-function mutants confirm the importance of apical residues to
      the primary interaction of human glycoprotein VI with collagen.
AB  - BACKGROUND: By site-directed mutagenesis of recombinant receptor fragments, we
      have previously identified residue lysine59 of the platelet collagen receptor
      glycoprotein VI (GPVI) as being critical for its interaction with the synthetic
      ligand collagen-related peptide (CRP) and the inhibitory phage antibody 10B12.
      Lysine59 is proposed to lie on the apical surface of the receptor near the linker
      joining the two immunoglobulin (Ig)-like extracellular domains. Recently, others
      have postulated the involvement of a portion of the first domain distant from the
      interdomain hinge as being involved in an extended collagen-binding site. AIM AND
      METHODS: To extend our knowledge of the primary collagen-binding site of GPVI, a
      number of neighboring residues on the apical surface of recombinant soluble GPVI
      were mutated to alanine and binding of these mutants, as well as the lysine59
      mutant, to fibrillar collagen was measured. RESULTS: Binding of recombinant GPVI
      to collagen, like CRP, was dramatically reduced by the mutation of residue
      lysine59 to glutamate. Remarkably, the mutation of residues arginine60 in domain
      one and arginine166 in domain two, individually to alanine, which had no
      significant affect on CRP binding, reduced binding of recombinant GPVI to
      collagen. Mutation of the residue lysine41 to alanine dramatically increased
      binding to both CRP and collagen. This mutation abolished 10B12 binding,
      confirming its position in the epitope of our inhibitory phage antibody.
      CONCLUSIONS: Residues lysine59, arginine60, and arginine166, from both Ig-like
      domains of GPVI, are critical for collagen binding by the receptor. This provides
      additional evidence for a basic patch on the apical surface of the receptor as
      the primary collagen-binding site of GPVI.

PMID- 16405524
TI  - It all depends on you.

PMID- 16405522
TI  - Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism.
AB  - BACKGROUND: Controversy exists about the indication of thrombolytic therapy in
      the subgroup of hemodynamically stable patients with acute pulmonary embolism
      (PE) and right ventricular dysfunction. Brain natriuretic peptide (BNP) is
      excreted from the cardiac ventricles in response to cardiomyocyte stretch and can
      be measured with an easy-to-perform blood test. OBJECTIVE: The objective of this
      study was to determine the predictive value of elevated BNP levels for early
      recurrent venous thromboembolism with or without fatal outcome in hemodynamically
      stable patients with acute PE. In addition, we assessed the potential clinical
      consequences of initiating thrombolytic therapy based on the BNP levels alone.
      METHODS: A nested case-control study was performed within the framework of a
      large randomized-controlled trial totalling 2213 hemodynamically stable patients
      with confirmed acute, symptomatic PE. Ninety patients experienced a fatal or non
      fatal recurrent venous thromboembolism during the first 3 months of follow-up
      (cases); Two hundred and ninety-seven patients with uneventful follow-up served
      as controls. Blood for BNP levels was obtained at referral and assayed in a
      central laboratory. RESULTS: Cases had significantly higher mean baseline BNP
      levels (P = 0.0002). The odds ratio (OR) for every logarithmic (log) unit
      increase in BNP concentration was 2.4 (95% CI: 1.5-3.7). A BNP cut-off level of
      1.25 pmol L(-1) [the optimal point on the receiver-operating characteristic (ROC)
      curve] was associated with a sensitivity and specificity of 60% and 62%,
      respectively. In theory, for every patient correctly receiving thrombolytic
      therapy at this cut-off, 16 patients will receive this therapy unnecessarily.
      CONCLUSIONS: Brain natriuretic peptide level at presentation is significantly
      associated with early (fatal) recurrent venous thromboembolism in hemodynamically
      stable patients with acute PE. However, this relationship appears clinically
      insufficient to guide the initiation of thrombolytic therapy.

PMID- 16405525
TI  - PRO: Empiric treatment with PPIs is not appropriate without testing.

PMID- 16405526
TI  - CON: Treatment with PPIs should not be preceded by pH monitoring in patients
      suspected of laryngeal reflux.

PMID- 16405527
TI  - A BALANCING VIEW: Empiric PPI therapy remains the champ, but not by a knock out!

PMID- 16405528
TI  - Barrett's esophagus is common in older men and women undergoing screening
      colonoscopy regardless of reflux symptoms.
AB  - BACKGROUND: Although Barrett's esophagus (BE) is the precursor of esophageal
      adenocarcinoma (ACA), most patients with ACA present outside of a BE surveillance
      program. This could be due to undiagnosed symptomatic GER and BE or BE/ACA
      occurring in patients without reflux symptoms. We have, therefore, studied the
      prevalence of BE and symptom status in older patients referred for colonoscopy.
      METHODS: All patients referred for outpatient colonoscopy were eligible if they
      were at least 65 yr old and had not previously undergone esophagoscopy. After
      informed consent, the patients completed detailed GER questionnaires. During the
      research endoscopy, the endoscopist recorded the squamocolumnar junction (SCJ) as
      either long-segment BE (LSBE), short-segment BE (SSBE), or normal. If the SCJ was
      felt to be "irregular" the endoscopist was asked to predict, in their judgment,
      if BE was present. All patients had biopsies below the SCJ, which were examined
      by a gastrointestinal pathologist who was blinded to the endoscopic findings.
      RESULTS: BE esophagus was present in 50 of the 300 patients studied (16.7%). BE
      was more common in men (35 of 161, 21.7%) than in women (15 of 139, 10.8%) (p <
      0.025). GERD symptoms were reported in 106 patients (35%) and BE was present in
      19.8% of symptomatic and 14.9% of asymptomatic cases (NS). The majority of the BE
      in this study was less than 3 cm in length (92%). The questionnaires did not
      predict the presence of BE. CONCLUSIONS: BE is common in unscreened male and
      female patients at least 65 yr of age who are referred for colonoscopy. Men were
      more likely than women to have BE although it occurred in both sexes. Reflux
      symptoms were fairly common but a poor predictor of BE.

PMID- 16405529
TI  - Gastroesophageal reflux symptoms and well-being in a random sample of the general
      population of a Swedish community.
AB  - OBJECTIVES: There is limited information on the relationship between
      gastroesophageal reflux symptoms and well-being in the general population. This
      study aimed to investigate this relationship and determine the severity threshold
      at which reflux symptoms meaningfully affect patients' well-being. METHODS: A
      random sample of the population of Malmo, Sweden (n = 4,624), was sent the
      Gastrointestinal Symptom Rating Scale, the Subjective Symptom Assessment Profile,
      and the Psychological General Well-Being Index. The relationship between well
      being and the severity of heartburn, acid regurgitation, stomach pain, and
      abdominal pain was investigated by analysis of covariance (ANCOVA). RESULTS:
      Complete data were obtained from 1,476 subjects (43% male; mean age [standard
      deviation], 49.9 [14.2] yr). The mean Psychological General Well-Being Index
      score was 102 (95% CI: 101-103). Increasing symptom severity was associated with
      a decrease in well-being, and correlations between Psychological General Well
      Being Index score and symptom severity ratings were statistically significant. At
      least mild symptoms of heartburn or abdominal pain (a mean Gastrointestinal
      Symptom Rating Scale score of > or =3) were associated with a clinically
      meaningful reduction in well-being (a Psychological General Well-Being Index
      score of less than 98). CONCLUSIONS: Reflux symptoms are associated with impaired
      well-being in the general population. Individuals with symptoms that are mild or
      more severe report a meaningful reduction in well-being similar to that seen in
      other diseases. This may represent an appropriate threshold for patient selection
      in trials of GERD therapy and for more detailed evaluation of patients consulting
      with reflux symptoms in clinical practice.

PMID- 16405530
TI  - Genetic variants in matrix metalloproteinase genes are associated with
      development of gastric ulcer in H. Pylori infection.
AB  - BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) are a family of enzymes
      that degrade most of the macromolecules making up the extracellular matrix. H.
      pylori infection increases the secretion of MMPs in the gastric mucosa leading to
      severe mucosal damage. The aim of this study was to investigate if genetic
      variants in MMPs involved in the inflammatory response to H. pylori could
      predispose patients with chronic H. pylori infection to develop gastric ulcer
      disease. METHODS: A total of 599 H. pylori-infected patients undergoing
      gastroscopy were genotyped for 20 SNPs covering the MMP-1, -3, -7, and -9 genes
      by TaqMan technology. Haplotype and single marker analysis was conducted to
      assess associations with gastric ulcer disease. RESULTS: Carriage of allele G of
      the functional promoter variant MMP-7-181 was significantly associated with
      gastric ulcer conferring a 1.6-fold increased risk (95% CI: 1.0-2.6, p = 0.037).
      In addition, carriage of allele A of a coding SNP in exon 6 of MMP-9 confers a
      2.4-fold increased risk (95% CI: 1.0-2.6, p = 0.013) for gastric ulcer.
      CONCLUSION: The level of association found in this study is in agreement with the
      nature of a complex genetic disease. Genetic variations in the MMP-7 and -9 gene
      may be part of a complex genetic risk profile to develop gastric ulcer in chronic
      H. pylori infection. Further studies are warranted to elucidate the
      pathophysiological role of these genes in ulcerogenesis.

PMID- 16405531
TI  - Interaction between host gastric Sialyl-Lewis X and H. pylori SabA enhances H.
      pylori density in patients lacking gastric Lewis B antigen.
AB  - OBJECTIVES: We tested whether the interaction between host gastric Le(x) antigen
      and the SabA protein of H. pylori determined gastric colonization density.
      METHODS: A total of 145 H. pylori-infected patients were assessed for their
      bacterial density and gastric Le(b) and sialyl-Le(x) expression. Their
      corresponding H. pylori isolates were tested for babA2 and sabA genotype by PCR.
      The sabA-genopositive PCR products were sequenced to check for mutations
      affecting SabA expression. The BabA and SabA expressions of each isolate were
      confirmed by Western blotting. RESULTS: All 145 H. pylori isolates were babA2
      genopositive and expressed BabA. There were 116 (80%) sabA-genopositive isolates,
      but only 45 (31%) of the isolates expressed SabA. Sequence of sabA-genopositive
      PCR products was achieved in 92 isolates, of which 60% had regular CT repeat
      pairs and the other 40% had a unique deletion of the CT repeats. Neither the
      deletion nor the different CT repeat-pairs in the sabA region were totally
      correlated with SabA expression, defined by Western blotting. H. pylori density
      was higher in those expressing gastric sialyl-Le(x) antigen (which interacts with
      SabA) (p < 0.001) only in those patients expressing weak or no gastric Le(b)
      antigen (which would interact with BabA), not in those with evident expression of
      gastric Le(b) antigen. CONCLUSIONS: In Taiwan, H. pylori isolates are 100% BabA
      positive, but only 31% of them express SabA. The interaction between gastric
      sialyl-Le(x) and SabA of H. pylori determines the colonization density of
      patients expressing gastric Le(b) weakly or not at all.

PMID- 16405532
TI  - Usefulness of contrast-enhanced endoscopic ultrasonography in the differentiation
      between malignant and benign lymphadenopathy.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) is considered the most useful
      diagnostic modality for regional staging; however, it is still difficult to
      diagnose lymph node metastasis by EUS images only. In this study, we report the
      usefulness of contrast-enhanced EUS (CE-EUS) in the evaluation of benign lymph
      nodes (BLN) or malignant lymph nodes (MLN) based on blood flow patterns. SUBJECTS
      AND METHODS: In the retrospective study, CE-EUS was performed in 46 patients in
      whom EUS revealed lymph node in the mediastinum or abdominal cavity. The subjects
      consisted of 22 patients with BLN and 24 patients with MLN. The lesions were
      examined by EUS, and the maximal and minimal diameters of lymph nodes were
      measured. Thereafter, the shape and internal echoes were investigated, and the
      findings were morphologically classified based on Catalano's report. Enhancement
      effects and the diagnostic capability of CE-EUS were evaluated. In the
      prospective study, BLNs were differentiated from MLN using the enhancement
      patterns on CE-EUS based on the results of the retrospective study, and the
      diagnostic capability was evaluated. RESULTS: In the retrospective study, there
      were no significant differences in the maximal diameter and maximal/minimal
      diameter ratio between MLN and BLN. The morphology was classified into four
      types. Based on the morphological classification, the sensitivity, specificity,
      and accuracy rate were 88.2%, 77.3%, and 82.1%, respectively. On CE-EUS, the
      enhancement pattern was classified into three types. The BLN lesions showed
      uniform enhancement (19/22). In all patients with MLN, a defect of enhancement
      was observed (24/24). The sensitivity, specificity, and accuracy rate of CE-EUS
      were 100%, 86.4%, and 92.3%, respectively. In the prospective study, the
      sensitivity, specificity, and accuracy rate of CE-EUS were 100%, 81.8%, and
      92.0%, respectively. CONCLUSIONS: CE-EUS is useful for differentiating BLN from
      MLN.

PMID- 16405533
TI  - A prospective study comparing video capsule endoscopy with double-balloon
      enteroscopy in patients with obscure gastrointestinal bleeding.
AB  - OBJECTIVE: Obscure gastrointestinal bleeding from jejunal and ileal lesions
      remains undiagnosed using traditional imaging techniques (radiologic,
      endoscopic). This prospective study compares the diagnostic detection rate of
      small-bowel lesions using wireless video capsule endoscopy (VCE) with the
      detection rate using double-balloon enteroscopy (DBE) in patients with obscure
      gastrointestinal bleeding (OGIB). Tolerance, adverse events, endoscopic
      interventions, and prognosis were described as secondary aims. METHODS: Thirty
      five consecutive patients with obscure gastrointestinal bleeding were evaluated
      (22 males and 13 females; mean age 63.2 yr; range, 19-86 yr). The detection rates
      of the Given M2A wireless VCE and DBE were compared. RESULTS: Small-bowel
      abnormalities were detected using VCE in 28 (80%) of the 35 patients with OGIB,
      compared with 21 (60%) of the 35 patients using DBE (p = 0.01). Both examinations
      were well tolerated, but VCE was more acceptable to patients. No major adverse
      event occurred after either examination. Biopsies (n = 27), argon plasma
      coagulation (n = 19), tattoo injection (n = 8), and polypectomy (n = 2) were
      feasible with DBE when indicated in 27 of the 35 patients (77%). During a median
      (range) follow-up period of 5 (2-12) months, 26 (74%) patients remained
      clinically stable and did not require blood transfusions after DBE procedures.
      Eighteen (51%) of those who remained clinically stable had received APC therapy.
      CONCLUSIONS: High detection rates of the causes of OGIB are feasible with VCE and
      DBE. Although the detection rate of VCE was superior, our results indicate that
      the procedures are complementary; an initial diagnostic imaging employing VCE
      might be followed by therapeutic and interventional DBE.

PMID- 16405534
TI  - Argon plasma coagulation in the management of symptomatic gastrointestinal
      vascular lesions: experience in 100 consecutive patients with long-term follow
      up.
AB  - BACKGROUND: The long-term efficacy of argon plasma coagulation (APC) in the
      management of gastrointestinal vascular lesions has not been evaluated in a large
      and well-defined series. The impact of APC on transfusion requirements and
      hemoglobin, and technical parameters including complications and number of
      treatment sessions, is assessed in this series. METHODS: Patients who underwent
      APC for bleeding gastrointestinal vascular lesions were identified via
      interrogation of an established endoscopic database, excluding patients with
      radiation proctitis, tumors, residual polypectomy tissue and acute ulcer
      bleeding. Follow-up data were collected via interview with patients and referring
      doctors, review of medical records, and follow-up blood tests. RESULTS: One
      hundred patients were enrolled, males = 46, median age = 74 yr (range: 19-99 yr).
      Median follow-up time was 16 months (range: 4-47 months). Lesions treated were
      arteriovenous malformations (n = 74) and gastric antral vascular ectasia (n =
      26). Fifty-three patients required transfusion. In this group, median hemoglobin
      improved from 66 g/L (range: 35-114) to 111 g/L (range: 55-155, p < 0.001).
      Median transfusion velocity fell from 2 units/month (range: 0.1-6) to 0
      units/month (range: 0-4, p < 0.001). Transfusion requirement was abolished in
      77%. In non-transfusion-requiring patients, median hemoglobin improved from 105
      g/L (range: 58-143) to 123 g/L (range: 79-158, p < 0.001). No complications
      occurred. CONCLUSIONS: APC is effective and safe in the management of
      gastrointestinal vascular lesions.

PMID- 16405535
TI  - Endoscopic ultrasonography in patients with large gastric folds at endoscopy and
      biopsies negative for malignancy: predictors of malignant disease and clinical
      impact.
AB  - OBJECTIVES: The aims of the study were to assess in patients with large gastric
      folds at endoscopy and endoscopic biopsies that tested negative for malignancy:
      (i) the predictive variables of malignancy in endoscopic ultrasonography (EUS),
      (ii) the impact of EUS. METHODS: Patients with this condition evaluated with
      radial EUS (following the standard study protocol of our Unit in these patients)
      during a 5-yr period were included. Nine variables were evaluated as possible
      predictors of malignancy (chi2, t-test, and logistic regression procedure) using
      pathology results, or a minimum of 2 yr of follow-up as gold standard. Likelihood
      ratios (LR), pre-EUS, and post-EUS probabilities for the diagnosis of malignancy
      were used to assess the clinical impact of the technique. RESULTS: Sixty-one
      patients were included (40 benign and 21 malignant). Predictive factors of
      malignancy were as follows: thickened gastric wall, thickened deep layers,
      impaired gastric distension, loss of the wall structure, and presence of ascites
      or lymph nodes, whereas the enlargement of superficial layers was a predictor of
      a benign condition. The enlargement of deep layers, as assessed by EUS was the
      only independent predictive factor for malignancy. When using this parameter, the
      pre-EUS probability of malignancy in our series (34%) increased up to 95% when
      EUS suggested malignancy (positive LR = 45), whereas it decreased to 4.7% when
      EUS precluded this diagnosis (negative LR = 0.102). CONCLUSIONS: (i) The
      enlargement of deep layers is the only independent predictive factor for
      malignancy in patients with large gastric folds at endoscopy and biopsies testing
      negative for malignancy and (ii) EUS has a high clinical impact in these
      patients.

PMID- 16405536
TI  - Oral glucose tolerance test predicts prognosis of patients with liver cirrhosis.
AB  - OBJECTIVE: The aim of this study was to evaluate whether oral glucose tolerance
      test (OGTT) was useful in evaluating the prognosis of patients with liver
      cirrhosis. METHODS: Fifty-six patients with liver cirrhosis were enrolled in a
      prospective cohort study. In all cases, glucose tolerance was diagnosed by a 75-g
      OGTT according to World Health Organization (WHO) criteria. The relationship of
      clinical variables to the cirrhosis-related prognosis was investigated using
      univariate and multivariate regression models. RESULTS: Diabetes mellitus (DM)
      was diagnosed in 21 subjects (38%), impaired glucose tolerance (IGT) in 13
      subjects (23%), and normal glucose tolerance (NGT) in 22 subjects (39%) using
      OGTT. The cumulative survival rates of patients with liver cirrhosis and NGT were
      94.7% at 5 yr; liver cirrhosis and IGT, 68.8% at 5 yr; liver cirrhosis and DM,
      56.6% at 5 yr. The survival rates of patients with liver cirrhosis and DM
      significantly differed from those with NGT. Univariate analysis demonstrated that
      serum albumin, total bilirubin, prothrombin activity, Child-Pugh scores, and
      glucose intolerance were highly significant prognostic factors. Multiple
      regression analysis yielded albumin and DM as the most powerful independent
      negative predictors of survival. CONCLUSIONS: OGTT appears to be useful for
      evaluating the prognosis of cirrhotic patients.

PMID- 16405537
TI  - The prevalence and predictors of elevated serum aminotransferase activity in the
      United States in 1999-2002.
AB  - OBJECTIVES: The presence of elevated serum aminotransferase activity is a sign of
      possible underlying liver disease. We aimed to describe the prevalence and
      associations of elevated serum aminotransferase activity in a recent, nationally
      representative U.S. survey. METHODS: We described the prevalence and predictors
      of elevated alanine aminotransferase (ALT >43 IU/L) or elevated aspartate
      aminotransferase (AST >40 IU/L) activity among 6,823 participants of the National
      Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002.
      We compared our findings to the results already published based on the NHANES
      conducted between 1988 and 1994. RESULTS: In NHANES 1999-2002, the prevalences of
      elevated ALT, AST, or either ALT or AST were 8.9%, 4.9%, and 9.8%, respectively,
      in the entire population and 7.3%, 3.6%, and 8.1%, respectively, after excluding
      participants who tested positive for hepatitis C virus (HCV) antibody or reported
      excessive alcohol consumption. Strong predictors of elevated ALT activity
      included increasing waist circumference and body mass index, alcohol consumption,
      male sex, Mexican American ethnicity, decreasing age, and presence of HCV
      antibody. In NHANES 1988-1994, which employed a different assay methodology, the
      prevalences of elevated aminotransferases were approximately half of the
      prevalences we describe in NHANES 1999-2002, but the predictors of elevated ALT
      activity were similar. CONCLUSIONS: The current prevalence of elevated ALT
      activity in the United States (8.9%) is more than double that of previously
      available estimates. This prevalence is very high (7.3%) even among persons
      without viral hepatitis C or excessive alcohol consumption and is strongly
      associated with risk factors for nonalcoholic fatty liver disease.

PMID- 16405538
TI  - Pathogenesis and treatment of Budd-Chiari syndrome combined with portal vein
      thrombosis.
AB  - OBJECTIVES: Combined Budd-Chiari syndrome and Portal Vein Thrombosis (BCS-PVT) is
      a challenging clinical condition with as yet unknown outcome. The aim of the
      present study was to investigate etiology, treatment options, and prognosis of
      patients with BCS-PVT. METHODS: Patients diagnosed with nonmalignant BCS between
      1984 and 2001 were identified in a large international study and classified into
      isolated BCS (n = 204), BCS-PVT without spleno-mesenteric vein thrombosis (SMVT;
      n = 15), and BCS-PVT with SMVT (n = 18). RESULTS: Multifactorial etiology was
      present in 58% of patients with combined BCS-PVT. Number of etiological factors
      increased significantly with the extent of thrombosis (p = 0.002). Main treatment
      options included anticoagulation and portosystemic shunting, of which extended
      TIPS showed the most beneficial results. Five-year survival was 59% (95% CI 39
      80%) in BCS-PVT versus 85% (95% CI 76-88%) in isolated BCS (p = 0.11). Survival
      tended to be worse in BCS-PVT patients with SMVT as compared to patients without
      SMVT (RR = 3.47, p = 0.11). CONCLUSIONS: In BCS, extension of thrombosis into the
      splanchnic venous bed was significantly related to the number of etiological
      factors, and was associated with poor outcome. These results strongly support a
      liberal use of anticoagulants, which so far had been widely debated.
      Alternatively, derivative shunt procedures appear difficult, yet not impossible.

PMID- 16405539
TI  - Effect of the etiology of viral cirrhosis on the survival of patients with
      hepatocellular carcinoma.
AB  - OBJECTIVES: The aim of this study was to assess whether hepatocellular carcinoma
      occurring in the setting of hepatitis B or C virus infection has different
      prognosis. METHODS: We performed a multicentric case-control study comparing 102
      pairs of patients affected by hepatitis B virus- or hepatitis C virus-related
      hepatocellular carcinoma. Patients were matched for sex (male/female: 84/18
      pairs), age, center, and period of enrollment, underlying chronic liver disease
      (cirrhosis/chronic hepatitis: 97/5 pairs), Child-Pugh class (A/B/C: 70/25/7
      pairs), hepatocellular carcinoma stage (nonadvanced/advanced: 50/52 pairs) and,
      when possible, modality of cancer diagnosis (75 pairs: 47 during and 28 outside
      surveillance). RESULTS: In the whole population, patients with hepatitis B tended
      to have a poor prognosis than those with hepatitis C (p = 0.160), and this
      difference became statistically significant among the patients with an advanced
      hepatocellular carcinoma (p = 0.025). Etiology, Child-Pugh class, gross
      pathology, and alpha-fetoprotein were the significant independent prognostic
      factors in the whole population. The distribution of these prognostic factors did
      not differ between patients with hepatitis B or hepatitis C, both in the whole
      population and in the subgroup of advanced hepatocellular carcinomas. CONCLUSION:
      Hepatitis B virus-related hepatocellular carcinomas have a greater aggressiveness
      than hepatitis C virus-related tumors, which becomes clinically manifest once
      they have reached an advanced stage.

PMID- 16405540
TI  - Increased expression of the chemokine fractalkine in Crohn's disease and
      association of the fractalkine receptor T280M polymorphism with a fibrostenosing
      disease Phenotype.
AB  - BACKGROUND: The fractalkine receptor CX3CR1 has been shown to be involved in
      inflammation and immune response. Recently, two polymorphisms of CX3CR1 (V249I
      and T280M) were reported. AIMS: Our aim was to analyze fractalkine expression and
      the role of CX3CR1 polymorphisms in Crohn's disease (CD). METHODS: We determined
      fractalkine mRNA expression in the intestinal epithelial cell (IEC) line SW480
      after stimulation with proinflammatory cytokines as well as in inflamed (n = 14)
      and noninflamed (n = 14) CD lesions by quantitative PCR. By restriction fragment
      length polymorphism analysis, genomic DNA from 206 patients with CD and 211
      unrelated controls was analyzed for the two single nucleotide polymorphisms in
      the CX3CR1 gene, which result in the V249I and T280M substitutions. RESULTS: All
      proinflammatory stimuli (TNF-alpha, IL-1beta, LPS) significantly increased
      fractalkine mRNA expression in IEC. There was also a significant increase in
      fractalkine mRNA expression in inflamed lesions of CD patients when compared to
      noninflamed colonic mucosa (p = 0.02). Intestinal fractalkine mRNA levels
      correlated highly with IL-8 mRNA expression levels (r = 0.931). However, there
      was no difference in the V249I and T280M genotype frequencies between CD patients
      and the control group. In the CD group, 33.0% were heterozygous and 8.3%
      homozygous for the V249I polymorphism, while 23.3% were heterozygous and 4.4%
      homozygous for the T280M polymorphism. All T280M homozygotes were diagnosed of
      intestinal stenosis (p = 0.03 vs wildtype and heterozygous carriers) and had
      significantly more often ileocolonic involvement more often than patients with
      wildtype and heterozygous genotypes (p = 0.01). These associations were
      independent of the CARD15 genotype status. CONCLUSIONS: The expression of the
      chemokine fractalkine is upregulated by proinflammatory cytokines and enhanced in
      inflamed CD lesions. The CX3CR1 T280M polymorphism appears to influence CD
      phenotype and localization.

PMID- 16405542
TI  - Hospitalization, surgery, and readmission rates of IBD in Canada: a population
      based study.
AB  - BACKGROUND: We aimed to define the rates of hospitalization and readmission for
      inflammatory bowel disease in Canada. METHODS: The data source was Statistics
      Canada Person Oriented Information Database (1994-2001). The number of stays for
      a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) by ICD-9-CM code
      555 or 556 was extracted (and assessed when CD or UC was the first diagnosis or
      was 1 of 16 diagnoses on the patient discharge abstract). Age-, gender-, and
      disease-specific rates of hospitalization, length of stay, readmission, and
      surgery were assessed. RESULTS: The age-adjusted hospitalization rate for CD
      declined over 1994-2001 from 29.2 to 26.9/100,000 but was stable for UC at 12.6
      13.3 per 100,000. In the 7 yr, 39.4% of CD patients (21.3-24.0%/yr) and 33.7% of
      UC patients (18.5-20.3%/yr) got readmitted at least once. The average length of
      stay declined from 10.3 (1994-1995) to 9.1 days (2000-2001) (p = 0.029) in CD and
      in UC declined from 12.2 to 10.1 days (p = 0.054). Of all hospitalizations, major
      surgery occurred in 48% of CD (44.8-49.8% per yr) and 55% of UC (51.5-59.0% per
      yr). CONCLUSIONS: Rates of hospitalization declined slightly for CD over the 7 yr
      but still remained twice as great as the rates for UC. Approximately 20% of CD
      and UC subjects got readmitted per year and over 7 yr approximately 35% got
      readmitted. Major surgery was a more common reason for hospitalization in UC than
      in CD.

PMID- 16405541
TI  - Molecular stratification of Crohn's disease by chemokine receptors: fractalkine
      receptor polymorphisms define a fibrostenosing ileal subgroup.
AB  - The association of NOD2/CARD15 gene mutations with Crohn's disease (CD) has also
      provided proof of principle that anatomic location (ileal disease) and
      stricturing behavior is associated with specific genetic variants. However, the
      majority of CD patients of Caucasian descent, and essentially all minority CD
      patients do not possess NOD2/CARD15 mutations. Although these early lessons from
      NOD2/CARD15 genotype/phenotype correlations are encouraging, much more needs to
      be done to adequately understand the CD spectrum of subgroups. The study by Brand
      et al. demonstrates that a chemokine receptor polymorphism (CX3CR1 T280) can also
      influence disease location and behavior, suggesting yet another genetic variant
      that can help to subgroup CD patients. Findings similar to the study by Brand and
      colleagues in this issue of American Journal of Gastroenterology suggest that
      panels of susceptibility alleles and polymorphisms will ultimately allow an early
      genetic determination that will correspond with unique clinical patterns of CD:
      increased expression of the chemokine fractalkine in Crohn's disease and
      association of the factalkine receptor T280M polymorphism with a fibrostenosing
      disease phenotype.

PMID- 16405543
TI  - A double-blind placebo-controlled study of the effects of the bisphosphonate
      risedronate on bone mass in patients with inflammatory bowel disease.
AB  - BACKGROUND: Low bone density and fractures are common in patients with
      inflammatory bowel disease (IBD). OBJECTIVE: To determine whether the
      bisphosphonate risedronate and calcium are safe and effective in preserving bone
      mass compared to calcium alone in IBD patients with low bone mass. PATIENTS:
      Sixty-one ambulatory patients with Crohn's disease (n = 31) or ulcerative colitis
      (n = 30) and low bone density. METHODS: Using a double-blind placebo-controlled
      trial format, patients were randomized to 12 months of therapy with risedronate 5
      mg or placebo. All received a 600 mg calcium supplement. Bone density using dual
      energy X-ray absorptiometry was performed at baseline and at 12 months. Disease
      activity, use of corticosteroid, and adverse events were noted. RESULTS: Forty
      eight patients completed the trial. Compared to the placebo group risedronate
      resulted in a 2.0% (95%CI, 0.02-3.97) and 1.9% (95%CI, 0.21-3.62) improvement in
      bone density at the spine and hip, respectively. IBD diagnosis, gender, therapy,
      and disease status had no effect on the results. There were no significant
      differences in the adverse events. CONCLUSIONS: Risedronate improved bone density
      at the spine and hip in patients with either Crohn's disease or ulcerative
      colitis and low bone mass. These data suggest that risedronate is a safe and
      effective therapy to improve bone mass in these patients.

PMID- 16405545
TI  - Diffusion-weighted MR imaging in the evaluation of pancreatic exocrine function
      before and after secretin stimulation.
AB  - OBJECTIVES: To evaluate diffusion weighted MR imaging before and after secretin
      stimulation in the assessment of pancreatic exocrine function in the setting of
      chronic pancreatitis. METHODS: Nine patients with severe chronic pancreatitis and
      sixteen patients without chronic pancreatitis but with a history of chronic
      alcohol consumption were enrolled in the chronic pancreatitis and risk groups,
      respectively. Thirty-eight patients without any pancreatic disease or history of
      alcohol consumption were included in the control group. Diffusion weighted images
      were obtained before and after secretin administration in all patients. The peak
      ADC values and times were determined and intergroup differences were compared. A
      receiver operating characteristic curve (ROC) was used to identify the cutoff
      values of the peak ADC times for discrimination of control group from risk and
      chronic pancreatitis groups. RESULTS: In the control group, a peak increase in
      ADC value of 57-120% (median: 75%) was observed between 90 s and 4 min (median: 2
      min) after administration of secretin (Pattern 1). In the risk group, in 13
      patients, a peak increase of 52-150% was observed between 4 and 8 min (median: 7
      min; Pattern 2). Peak times were significantly longer in risk group (p < 0.01).
      In three patients in the risk group, and in all patients in the chronic
      pancreatitis group, no ADC peak was observed within 10 min following secretin
      administration (Pattern 3). Using a peak time of 4 min as the cut-off value, a
      sensitivity of 100% and specificity of 94.7% were achieved in discriminating the
      control group from the combined risk and chronic pancreatitis groups. CONCLUSION:
      Diffusion-weighted MR imaging before and after secretin administration could
      yield clinically useful information for detecting pathophysiologic alterations in
      the setting of chronic pancreatitis.

PMID- 16405544
TI  - Abdominal pain impacts quality of life in women with irritable bowel syndrome.
AB  - OBJECTIVES: Patients with irritable bowel syndrome (IBS) report lower health
      related quality of life (QoL) as compared to healthy controls. The aims of this
      analysis were to describe which IBS symptoms were rated on a daily diary as most
      distressing/severe by IBS women, and determine which IBS symptoms were most
      predictive of lower QoL and have the greatest impact on daily life. METHODS: This
      report is a secondary analysis of prospective and retrospective symptom severity
      and impact data, collected on 242 women with IBS, aged 18-48, who were studied
      between 1997 and 2004. RESULTS: On the daily diary, intestinal gas was the most
      frequent IBS symptom with subjects reporting at least minimal intestinal gas on
      74% of days and moderate or worse severity on 27% of days. Abdominal pain
      occurred at least minimally on 62% of days. Diarrhea was the least common. Across
      women, abdominal pain was most strongly related to life impact variables and QoL,
      followed by intestinal gas and bloating. Analysis of day-to-day variation within
      women showed that abdominal pain was most strongly correlated with daily life
      impact variables and constipation had the weakest correlation. While diarrhea had
      a lower correlation with life impact, this was due to the low prevalence of
      diarrhea. When it occurs, diarrhea has a large impact. Partial correlation
      analysis showed that the impact of diarrhea is independent of abdominal pain.
      CONCLUSION: Abdominal pain is the most disruptive IBS symptom. Diarrhea also has
      an independent and significant impact when it occurs, especially in those with
      diarrhea-predominant IBS.

PMID- 16405546
TI  - Exocrine pancreatic function: evaluation with MR imaging before and after
      secretin stimulation.
AB  - Secretin-stimulated magnetic resonance cholangiopancreatography (SS-MRCP)
      enhances standard pancreatic imaging in chronic pancreatitis. Diffusion-weighted
      MRI added to SS-MRCP allows a qualitative and potentially quantitative estimate
      of pancreatic exocrine secretion, providing an alternative to standard "tube"
      tests.

PMID- 16405547
TI  - Risk factors for post-ERCP pancreatitis: a prospective multicenter study.
AB  - OBJECTIVES: Pancreatitis is the most common and serious complication of
      diagnostic and therapeutic ERCP. The aim of this study is to examine the
      potential patient- and procedure-related risk factors for post-ERCP pancreatitis
      in a prospective multicenter study. METHODS: A 160-variable database was
      prospectively collected by a defined protocol on patients undergoing diagnostic
      or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and
      participating in a randomized controlled study evaluating whether prophylactic
      corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were
      collected prior to the procedure, at the time of procedure, and 24-72 h after
      discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according
      to consensus criteria. RESULTS: Of the 1,115 patients enrolled, diagnostic ERCP
      with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%)
      and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction
      (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis
      developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in
      45 (4%), and severe in 11(1%). There was no difference in the incidence of
      pancreatitis or the frequency of investigated potential pancreatitis risk factors
      between the corticosteroid and placebo groups. By univariate analysis, the
      incidence of post-ERCP pancreatitis was significantly higher in 19 of 30
      investigated variables. In the multivariate risk model, significant risk factors
      with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8),
      suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr
      (OR: 1.6), > or =2 contrast injections into the pancreatic duct (OR: 1.5), and
      trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic
      pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla
      sphincterotomy (either biliary or pancreatic) were not multivariate risk factors
      for post-ERCP pancreatitis. CONCLUSION: This study emphasizes the role of patient
      factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors
      (number of PD injections, minor papilla sphincterotomy, and operator experience)
      as the determining high-risk predictors for post-ERCP pancreatitis.

PMID- 16405548
TI  - Chronic pancreatic inflammation induced by environmental tobacco smoke inhalation
      in rats.
AB  - OBJECTIVE: Despite a strong epidemiological association between cigarette smoking
      and pancreatic diseases, such as pancreatic cancer and chronic pancreatitis, the
      effects of long-term cigarette smoke inhalation on the pancreas have not been
      clearly determined. In the present study, we investigated the effect of cigarette
      smoke inhalation on the pancreas. METHODS: Thirty-six female Sprague Dawley rats
      were exposed to two different doses of environmental tobacco smoke averaging 100
      mg or 160 mg/m3 total suspended particulate matter (TSP) per m3 for 70 min twice
      a day for 12 wk. The animals were sacrificed and examined for the effects of
      tobacco smoke exposure on pancreatic morphology and function. RESULTS: In 58%
      (7/12) of the animals, exposure to 160 mg/m3 TSP cigarette smoke induced a
      chronic pancreatic inflammatory process with fibrosis and scarring of pancreatic
      acinar structures. Animals with fibrotic alterations showed an induction of
      pancreatic pro-collagen 1 gene expression, and the infiltration of immune cells
      was accompanied by the expression of the inflammatory mediators MIP-1alpha, IL
      1beta, and TGF-beta in 33% (4/12) of the animals. Acinar cell stress was
      manifested by a significant up-regulation of pancreatitis-associated protein
      expression (PAP) in smoke-exposed animals (smoke-exposed 6,932 +/- 1,236 vs
      control 3,608 +/- 305, p < 0.05). Possibly contributing to the morphological
      damage to the exocrine pancreas, the inhalation of cigarette smoke induced
      trypsinogen and chymotrypsinogen gene expression and, furthermore, reduced
      pancreatic enzyme content. CONCLUSIONS: This study provides experimental evidence
      of morphological pancreatic damage induced by the inhalation of cigarette smoke,
      which is likely to be mediated by alterations of acinar cell function.

PMID- 16405549
TI  - Smoking--a trigger for chronic inflammation and cancer development in the
      pancreas.
AB  - Tobacco smoke, with its complexity of constituents, damages the pancreatic organ
      in multiple ways. Smoke not only affects pancreatic secretion patterns via its
      nicotine content but induces inflammatory reactions and exerts carcinogenic
      effects by several other constituents. Smoke enhances ethanol-induced pancreatic
      injury and accelerates the development and progression of chronic pancreatitis
      independent of etiology. Through the process of inflammation, smoking contributes
      to pancreatic carcinogenesis. The experiment of Wittel and colleagues published
      in this issue of the American Journal of Gastroenterology sheds further light on
      this topic by reporting in great detail two different kinds of pancreatic damage
      in rats exposed to high doses of smoke.

PMID- 16405550
TI  - Association of interleukin-1beta gene polymorphisms with precancerous gastric
      lesions in African Americans and Caucasians.
AB  - OBJECTIVE: Interleukin-1beta plays an important role in inflammation and gastric
      physiology. Polymorphisms of the IL1B gene have been associated with gastric
      atrophy and increased cancer risk, especially in Helicobacter pylori-infected
      subjects. The aim of this study was to evaluate the relationship between IL1B and
      IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic
      gastritis in African Americans and Caucasians. METHODS: Genomic DNA was extracted
      from gastric biopsies of 269 adult outpatients (172 African Americans and 97
      Caucasians) undergoing diagnostic upper gastrointestinal endoscopy. Histological
      diagnosis was evaluated according to the updated Sydney System and H. pylori
      status was assessed by Steiner silver stain. Polymorphisms of the IL1B gene (
      511, -31, and +3954) and the IL1 receptor antagonist were investigated by PCR
      RFLP. Logistic regression models were used to identify variables associated with
      multifocal atrophic gastritis in terms of odds ratios and 95% confidence
      intervals. RESULTS: Considering subjects with normal histology and nonatrophic
      gastritis as controls, a significant association was found between IL1B+3954T
      carrier and multiatrophic gastritis (OR 2.23, 95% CI 1.28, 3.88). Analyses
      stratified by ethnic group demonstrated similar associations in both African
      Americans (OR 2.23, 95% CI 1.14, 4.37) and Caucasians (OR 2.04, 95% CI 0.74,
      5.65). A positive but not significant association was found between the allele 2
      of the IL1RN and the presence of multifocal atrophic gastritis. The remaining
      proinflammatory polymorphisms were not associated with this precancerous lesion.
      CONCLUSIONS: Our results suggest that the presence of IL1B+3954T allele is a risk
      marker for multifocal atrophic gastritis in the population studied.

PMID- 16405551
TI  - Flat and depressed neoplasms of the colon in Western populations.
AB  - Flat and depressed neoplasms of the colon are defined endoscopically as visible
      non-exophytic, flat and/or depressed mucosal lesions with a height less than half
      the diameter of the lesion. These neoplasms are typically smaller than their
      polypoid counterparts, and might be associated with a more aggressive biological
      behavior. While these lesions have been described in cohorts of Japanese patients
      for over two decades, their existence in Western populations has been less well
      described. This review focuses on the epidemiology and biological behavior of
      flat and depressed neoplasms in Western populations as well as the strategies for
      their identification, endoscopic staging, and therapy.

PMID- 16405552
TI  - Fiber for the treatment of hemorrhoids complications: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: To evaluate the impact of laxatives on a wide range of symptoms in
      patients with symptomatic hemorrhoids. METHODS: We searched using the following
      sources: MEDLINE, EMBASE, CINAHL and CENTRAL, BIOSIS, AMED, Papers First and
      Proceedings; study authors, industry, and experts in the field. We included all
      published and unpublished parallel group randomized controlled trials comparing
      any type of laxative to placebo or no therapy in patients with symptomatic
      hemorrhoids. Two reviewers independently screened studies for inclusion,
      retrieved all potentially relevant studies, and extracted data on study
      population, intervention, prespecified outcomes, and methodology. RESULTS: Seven
      trials randomized 378 patients to fiber or a nonfiber control. Studies were of
      moderate quality for most outcomes. Meta-analyses using random effects models
      suggested that fiber has an apparent beneficial effect. The risk of not
      improving/persisting symptoms decreased by 47% in the fiber group (RR = 0.53, 95%
      CI 0.38-0.73) and the risk of bleeding by 50% (RR = 0.50, 95% CI 0.28-0.89).
      Studies with multiple follow-ups, usually at 6 wk and at 3 months, showed
      consistent results over time. Results are also compatible with large treatment
      effects in prolapse, pain, and itching, but even in the pooled analyses
      confidence intervals were wide and compatible with no effect (RR = 0.79, 95% CI
      0.37-1.67; RR = 0.33, 95% CI 0.07-1.65; and RR = 0.71, 95% CI 0.24-2.10,
      respectively). One study suggested a decrease in recurrence. Results showed a
      nonsignificant trend toward increases in mild adverse events in the fiber group
      (RR = 6.0, 95% CI 0.57-64.8). CONCLUSIONS: Trials of fiber show a consistent
      beneficial effect for symptoms and bleeding in the treatment of symptomatic
      hemorrhoids.

PMID- 16405553
TI  - Colonic perforation after computed tomographic colonography in a patient with
      fibrostenosing Crohn's disease.
AB  - Computed tomographic colonography (CTC) offers great promise in the management of
      patients with disorders of the colon. Few complications have been reported with
      its use thus far. We describe herein a case of colonic perforation during CTC in
      a patient with active stenosing ileocolonic Crohn's disease. To our knowledge,
      this is the first reported case of CTC-related perforation in the setting of
      Crohn's disease, and the third reported perforation overall. Perforation likely
      occurred in this case due to barotrauma in the setting of colonic strictures and
      an inflamed, weakened colonic wall. Physician awareness of the increased risk of
      perforation with CTC in the setting of inflammatory and/or obstructive disease of
      the colon will allow for improved clinical decision-making in the care of these
      patients.

PMID- 16405554
TI  - A novel germline mutation of MSH2 in a hereditary nonpolyposis colorectal cancer
      patient with liposarcoma.
AB  - BACKGROUND: One of the clinical features of hereditary nonpolyposis colorectal
      cancer (HNPCC) is a high incidence of multiple primary neoplasms arising in
      various organs including the gastrointestinal and genitourinary tracts. Among
      extracolonic tumors, a limited number of soft tissue sarcomas associated with
      HNPCC have been reported, and the mechanism underlying liposarcoma in HNPCC
      patients remains unclear. AIM: We herein report the case of a HNPCC patient with
      liposarcoma, with the goal of elucidating the involvement of a mismatch repair
      deficiency in the tumor. METHODS AND RESULTS: A 40-yr-old Japanese patient, who
      had a past history of adenocarcinoma of the rectum and transitional cell
      carcinoma of the urinary bladder, developed a liposarcoma in his left thigh.
      Although his family history did not fulfill the revised Amsterdam criteria, his
      blood sample was subjected to genetic testing. Direct sequencing of the genomic
      DNA from the blood identified an AT deletion at codon 677 in exon 13 of hMSH2, a
      pathogenic mutation that has not been reported before. The expression of MSH2 in
      the liposarcoma and rectal cancer of the patient was analyzed by
      immunohistochemistry, which revealed loss of MSH2 expression in the tumors. To
      investigate whether the loss of MSH2 was a common feature of liposarcoma, we
      examined the MSH2 expression in an additional two sporadic liposarcomas, both of
      which were stained with anti-MSH2 antibody. CONCLUSION: We identified a novel
      pathogenic germline mutation of MSH2 in an HNPCC patient. Since an
      immunohistochemical analysis showed no nuclear staining for MSH2 protein in the
      liposarcoma as well as the rectal cancer, the loss of wild-type MSH2 protein was
      thus considered to possibly play a role in the development of liposarcoma in
      HNPCC patients.

PMID- 16405555
TI  - Tongue and skin hyperpigmentation during PEG-interferon-alpha/ribavirin therapy
      in dark-skinned non-Caucasian patients with chronic hepatitis C.
AB  - Various skin disorders may occur during antiviral therapy with interferon (IFN)
      and ribavirin (RBV) for chronic hepatitis C. This article describes to our
      knowledge the first report of lingual hyperpigmentation during pegylated (PEG)
      IFN/RBV combination therapy in five dark-skinned hepatitis C virus (HCV)
      patients. Lingual pigmentation during antiviral therapy was not associated with
      age, gender, HCV genotype, doses of RBV, or duration of the treatment or
      treatment outcome. Since IFN increases the expression of alpha-melanocyte
      stimulating hormone (MSH) surface receptors, the use of PEG-IFN having a longer
      plasma half-life may even increase incidence for such cutaneous side effects
      particularly in dark-skinned HCV patients.

PMID- 16405557
TI  - RE: Odze RD. unraveling the mystery of the gastroesophageal junction: a
      pathologist's perspective.

PMID- 16405558
TI  - Consensus interferon induced interstitial pneumonitis in a patient with HCV.

PMID- 16405559
TI  - Achalasia: new insights in pathogenesis.

PMID- 16405560
TI  - Leukocytapheresis in ulcerative colitis.

PMID- 16405561
TI  - Persistent cholestatic jaundice after ERCP.

PMID- 16405562
TI  - Microsatellite instability in adenoma as a possible marker to identify HNPCC
      patients.

PMID- 16405564
TI  - Cutaneous melanoma: family screening and genetic testing.
AB  - The incidence of cutaneous melanoma (CM) has been steadily increasing in recent
      decades. Ultraviolet radiation (UVR) exposure, in the form of intermittent heavy
      exposure and severe sunburns in childhood, is believed to be the most important
      environmental contribution to CM risk. Genetic determinants also modulate CM
      risk, probably to a greater extent than environmental exposure. Certain heritable
      traits such as prominent numbers of common and atypical melanocytic nevi, skin
      type, dense UVR-induced freckling, and hair color are all known to be associated
      with increased CM risk. Very rarely, a heritable mutation in a high-risk gene
      renders the susceptible individual at extreme risk for CM. Families may carry one
      or more of the other high-risk phenotypic traits leading to uncertainty about how
      to quantify CM risk and provide management recommendations. Commercial genetic
      testing for the known high-risk inherited genetic mutations is available but is
      only relevant for those rare families likely to be carrying identifiable
      mutations. CM screening and risk intervention programs are being established
      internationally for families at markedly increased risk. Algorithms based on the
      level of risk are proposed.

PMID- 16405566
TI  - Cutaneous melanoma: available therapy for metastatic disease.
AB  - Survival of melanoma varies widely by stage, from a potentially highly curable
      disease when detected in early stages, to a disease with dismal prognosis when it
      reaches advanced inoperable stages. Stage IV melanoma defines distant metastasis
      and continues to comprise an ominous prognosis, with a median survival of 6-9
      months. Currently, there is no therapeutic agent known to prolong survival in
      patients with metastatic melanoma. Therapeutic approaches studied in metastatic
      melanoma include chemotherapy, biochemotherapy, nonspecific immune adjuvants,
      cancer-specific vaccines, cytokines, monoclonal antibodies, and specific
      immunostimulants. Chemotherapy with single-agent dacarbazine is the only United
      States Food and Drug Administration (US-FDA)-approved chemotherapy agent for
      metastatic melanoma. Immunological approaches have yielded the only newly US-FDA
      approved agent for metastatic disease in 30 years, high-dose bolus IL-2, based on
      durable responses in some patients with metastatic melanoma, but with associated
      high toxicity rate and cost. A number of novel therapeutic agents are undergoing
      active clinical investigation.

PMID- 16405565
TI  - Cutaneous melanoma: interferon alpha adjuvant therapy for patients at high risk
      for recurrent disease.
AB  - Systemic adjuvant therapy in melanoma patients is the systemic treatment that is
      administered with the goal of eradicating micrometastatic deposits in patients
      who are clinically free of disease after surgical removal of the primary
      melanoma, but with a high risk of systemic recurrence. Interferon-alpha (IFN
      alpha) is one of the most frequently used adjuvant therapies. Several randomized
      trials evaluated the efficacy of IFN-alpha in melanoma patients. However, results
      from conducted trials are controversial. Twelve randomized IFN-alpha trials are
      discussed in detail. All trials, including meta-analysis, failed to demonstrate a
      clear impact of IFN-alpha therapy on overall survival in melanoma patients. Based
      on currently available evidence, IFN-alpha therapy in the adjuvant setting should
      not be considered standard of care for patients who have melanoma. Results from
      ongoing studies are awaited. Further research for this therapy is required.

PMID- 16405567
TI  - Cutaneous melanoma: public health approach to early detection.
AB  - Melanoma is a major public health problem. There will be a projected 60,000 cases
      of invasive melanoma diagnosed in 2005, and that number is increasing each year.
      Fortunately, the prognosis is improving as well, but we still have approximately
      8000 deaths per year related to this tumor. To reduce this number of deaths, we
      need to look at the skin--inspect--and see--recognize potential early melanomas
      when we look at them. Most of the population does not see a dermatologist
      regularly, and there are many barriers to general clinicians inspecting the skin,
      including inadequacy of dermatologic skills. Patients are ultimately responsible
      for their own skin, but only a small proportion of people actually perform
      thorough skin self-examination on a recommended monthly basis. There are various
      tools used by some dermatologists to facilitate early detection, including total
      body and lesional photography and epiluminescence microscopy (dermoscopy) of
      lesions. A basic skin cancer triage algorithm has been developed and tested in
      primary care, with promising results for improving practice. The general
      population also needs better guidance on early melanoma detection. Hence, instead
      of relying on the "ABCDs" for a morphologic diagnosis, the message of "a new or
      changing skin lesion" is being promoted to facilitate early diagnosis of thin,
      curable tumors. Together, patients and clinicians can improve early detection to
      reduce melanoma-related mortality.

PMID- 16405568
TI  - Cutaneous melanoma: making a clinical diagnosis, present and future.
AB  - The minimum requirement for the general dermatologist for clinically assessing
      pigmented skin lesions is dermoscopy. In expert hands, this technique has been
      shown to improve both the sensitivity and specificity for the diagnosis of
      melanoma. This is also reflected by lower benign melanoma excision ratios and
      decreased excision rates. Evidence is mounting for the routine use of total body
      skin photography for patients with a very high risk of developing cutaneous
      melanoma. Both long-term (12 months) and short-term (3 months) digital dermoscopy
      monitoring has been shown to allow the detection of dermoscopically featureless
      melanoma and is central for the clinical assessment of melanocytic lesions at the
      Sydney Melanoma Diagnostic Center. The use of automated instruments for the
      diagnosis of cutaneous melanoma is still in an experimental phase, and its
      utility is dependent on the evidence that such instruments give a clinically
      useful expert second opinion. Currently, other noninvasive diagnostic techniques,
      such as in vivo confocal scanning laser microscopy, are reserved for clinical
      research settings.

PMID- 16405569
TI  - Distinguishing melanocytic nevi from melanoma by DNA copy number changes:
      comparative genomic hybridization as a research and diagnostic tool.
AB  - Cancer typically results in loosened control over genomic integrity, resulting in
      alterations of the genome of cancer cells. Comparative genomic hybridization
      (CGH) is a method that can be used on DNA extracted from routinely fixed tissue
      to assess the entire genome for the presence of changes in DNA copy number. CGH
      analysis has revealed that melanoma differs from melanocytic nevi by the presence
      of frequent chromosomal aberrations. In contrast, melanocytic nevi typically show
      no chromosomal aberrations, or have a restricted set of alterations with
      basically no overlap to melanoma. These marked differences between aberration
      patterns in melanomas and melanocytic nevi can be exploited diagnostically to
      classify melanocytic tumors that are ambiguous based on histopathologic
      assessment. In addition to potential diagnostic applications, detailed analyses
      of recurrent aberrations can lead to the identification of genes relevant in
      melanocytic neoplasia.

PMID- 16405570
TI  - Cutaneous melanoma and intervention strategies to reduce tumor-related mortality:
      what we know, what we don't know, and what we think we know that isn't so.
AB  - The care of patients who have cutaneous melanoma (CM) has undergone a dramatic
      change during the past five decades. In an increasing majority of cases, CM is
      being discovered in a premetastatic phase of tumor progression. Most patients are
      being treated in the ambulatory setting with a minimum of inconvenience and
      economic cost, and modest re-excision margins have largely replaced the
      mutilating surgical exonerations that were once standard only four decades ago.
      Histopathologic assessment of the primary tumor is the most widely used staging
      procedure to determine who is most likely to develop metastatic disease. For
      patients who develop distant metastases, there is no therapy currently available,
      based on large-scale randomized trials, that will prolong patient survival.
      Therefore, establishing an early diagnosis in a premetastatic phase of tumor
      development must be the overriding goal of any intervention strategy that seeks
      to reduce CM-related mortality. Unfortunately, as a result of public messages
      that emphasize the role of ultraviolet radiation (UVR) exposure in tumor
      development, most general physicians and lay people believe that most if not all
      cases of CM are the direct result of UVR exposure. In fact, we do not know the
      case fraction of CM directly attributable to UVR, and the unintended consequences
      of current messages directly linking UVR exposure and CM development may be
      thwarting the primary intervention goal of reducing tumor-related mortality. More
      likely to have an immediate positive impact on CM-related mortality are public
      messages that encourage skin awareness and self-examination by patients, total
      skin screening examinations by physicians during routine care, and periodic
      lifetime surveillance of patients determined to have a high CM risk based on
      identifiable historic and phenotypic traits.

PMID- 16405571
TI  - Variation in synonymous codon use and DNA polymorphism within the Drosophila
      genome.
AB  - A strong negative correlation between the rate of amino-acid substitution and
      codon usage bias in Drosophila has been attributed to interference between
      positive selection at nonsynonymous sites and weak selection on codon usage. To
      further explore this possibility we have investigated polymorphism and divergence
      at three kinds of sites: synonymous, nonsynonymous and intronic in relation to
      codon bias in D. melanogaster and D. simulans. We confirmed that protein
      evolution is one of the main explicative parameters for interlocus codon bias
      variation (r(2) approximately 40%). However, intron or synonymous diversities,
      which could have been expected to be good indicators of local interference [here
      defined as the additional increase of drift due to selection on tightly linked
      sites, also called 'genetic draft' by Gillespie (2000)] did not covary
      significantly with codon bias or with protein evolution. Concurrently, levels of
      polymorphism were reduced in regions of low recombination rates whereas codon
      bias was not. Finally, while nonsynonymous diversities were very well correlated
      between species, neither synonymous nor intron diversities observed in D.
      melanogaster were correlated with those observed in D. simulans. All together,
      our results suggest that the selective constraint on the protein is a stable
      component of gene evolution while local interference is not. The pattern of
      variation in genetic draft along the genome therefore seems to be instable
      through evolutionary times and should therefore be considered as a minor
      determinant of codon bias variance. We argue that selective constraints for
      optimal codon usage are likely to be correlated with selective constraints on the
      protein, both between codons within a gene, as previously suggested, and also
      between genes within a genome.

PMID- 16405572
TI  - Contrasting effects of long distance seed dispersal on genetic diversity during
      range expansion.
AB  - Currently many attempts are made to reconstruct the colonization history of plant
      species after the last ice age. A surprising finding is that during the
      colonization phase genetic diversity did not decrease as much as expected. In
      this paper we examine whether long distance seed dispersal events could play a
      role in the unexpected maintenance of genetic diversity during range expansion.
      This study is based on simulations carried out with a maternally inherited
      haploid locus using a cellular automaton. The simulations reveal a close
      relationship between the frequency of long distance seed dispersal events and the
      amount of genetic diversity preserved during colonization. In particular, when
      the colonized region is narrow, a complete loss of genetic diversity results from
      the occurrence of very rare long distance dispersal (LDD) events. We call this
      phenomenon the 'embolism effect'. However, slightly higher rates of LDD events
      reverse this effect, up to the point that diversity is better preserved than in a
      pure diffusion model. This phenomenon is linked to the reorganization of the
      genetic structure during colonization and is called the 'reshuffling effect'.

PMID- 16405573
TI  - The geographic mosaic in predispersal interactions and selection on Helleborus
      foetidus (Ranunculaceae).
AB  - We examine the hierarchical geographic structure of the interaction between a
      plant, Helleborus foetidus, and its floral herbivores and pollinators
      (interactors). Six populations from three distant regions of the Iberian
      Peninsula were used to examine intra- and inter-regional variation in plant
      traits, interactors and plant fecundity, and to compare, through selection
      gradient and path analyses, which traits were under selection, and which
      interactors were responsible for differential selection. Geographic and temporal
      congruency in interactor-mediated selection was further tested using a recent
      analytical approach based on multi-group comparison in Structural Equation
      Models. Most plant traits, interactors and fecundity differed among regions but
      not between populations. Similarly, the identity of the traits under selection,
      the selection gradients (strength and/or the direction of the selection) and the
      path coefficients (identifying the ecological basis for selection) varied inter-
      but not intra-regionally. Results show a selection mosaic at the broad scale and,
      for some traits, a link of differential selection to trait differentiation.

PMID- 16405575
TI  - Host ploidy, parasitism and immune defence in a coevolutionary snail-trematode
      system.
AB  - We studied the role of host ploidy and parasite exposure on immune defence
      allocation in a snail-trematode system (Potamopyrgus antipodarum-Microphallus
      sp.). In the field, haemocyte (the defence cell) concentration was lowest in deep
      water habitats where infection is relatively low and highest in shallow-water
      habitats where infection is common. Because the frequency of asexual triploid
      snails is positively correlated with depth, we also experimentally studied the
      role of ploidy by exposing both diploid sexual and triploid asexual snails to
      Microphallus eggs. We found that triploid snails had lower haemocyte
      concentrations than did diploids in both parasite-addition and parasite-free
      treatments. We also found that both triploids and diploids increased their
      numbers of large granular haemocytes at similar rates after parasite exposure.
      Because triploid P. antipodarum have been shown to be more resistant to
      allopatric parasites than diploids, the current results suggest that the
      increased resistance of triploids is because of intrinsic genetic properties
      rather than to greater allocation to defence cells. This finding is consistent
      with recent theory on the advantages of increased ploidy for hosts combating
      coevolving parasites.

PMID- 16405574
TI  - Measuring natural and sexual selection on breeding values of male display traits
      in Drosophila serrata.
AB  - Fundamental to many theories of sexual selection is the expectation that sexual
      traits, which males use in an attempt to increase mating success, confer costs as
      well as benefits to individual males. Although evolution of exaggerated male
      traits is predicted to be halted, by costs applied by natural selection, there is
      a lack of empirical work devoted to quantitatively establishing whether natural
      selection opposes sexual selection generated by the preferences of females. In
      this study, we quantified natural and sexual selection gradients on breeding
      values for cuticular hydrocarbon (CHC) components of male contact pheromones in
      Drosophila serrata. As male sexual traits may often be environmentally condition
      dependent, breeding values were used in the selection analysis to remove the
      possibility of environmental correlations between the measured trait and fitness
      biasing estimates of selection. The direction of natural selection was found to
      oppose sexual selection on a subset of CHCs examined. Opposing natural and sexual
      selection suggests that further evolution of the male pheromone may in part be
      limited by costs associated with attractive male CHC blends.

PMID- 16405576
TI  - Evolution of handling time can destroy the coexistence of cycling predators.
AB  - Several consumers (predators) with Holling type II functional response may
      robustly coexist even if they utilize the same resource (prey), provided that the
      population exhibits nonequilibrium dynamics and the handling time of predators is
      sufficiently different. We investigate the evolution of handling time and, in
      particular, its effect on coexistence. Longer handling time is costly in terms of
      lost foraging time, but allows more nutrients to be extracted from a captured
      prey individual. Assuming a hyperbolically saturating relationship between
      handling time and the number of new predators produced per prey consumed, we
      obtain three results: (i) There is a globally evolutionarily stable handling
      time; (ii) At most two predator strategies can coexist in this model; (iii) When
      two predators coexist, a mutant with intermediate handling time can always
      invade. This implies that there is no evolutionarily stable coexistence, and the
      evolution of handling time eventually leads to a single evolutionarily stable
      predator. These results are proven analytically and are valid for arbitrary (not
      only small) mutations; they however depend on the relationship between handling
      time and offspring production and on the assumption that predators differ only in
      their prey handling strategy.

PMID- 16405577
TI  - Timing and tempo of primate speciation.
AB  - Published molecular clocks for primates are used to estimate typical divergence
      times for phylogroups (1.6 Ma), species (3.3 Ma), sister species (2.7 Ma), genera
      (8.9 Ma) and sister genera (8.6 Ma). Significant median differences exist between
      major groups (infraorders and superfamilies) for various divergence times. These
      data are employed to estimate typical maximum duration of speciation. Typical
      primate values (1.1 Ma) suggest this process to be faster than is characteristic
      of many vertebrates. However, after considering divergence times for hybridizing
      congeneric and confamilial primates, this value is likely only to estimate the
      commencement of prezygotic isolating mechanisms, rather than the completion of
      reproductive isolation. Thus, speciation typically takes around 1.0 Ma to more
      than 4.0 Ma to occur, depending on whether prezygotic or post-zygotic isolating
      mechanisms are emphasized. Typical primate genus age is around 5.3 Ma, but we
      note differences among major groups. In light of these estimates, the
      classification of humans and chimpanzees is reconsidered using a molecular
      yardstick approach. Three taxonomic frameworks may flow from molecular analyses,
      all of them having major implications for understanding the evolution of humans
      and chimpanzees.

PMID- 16405578
TI  - Life history evolution in cichlids 1: revisiting the evolution of life histories
      in relation to parental care.
AB  - Empirical links between egg size and duration of parental care in fishes have
      generated a considerable amount of theory concerning life history evolution.
      However, to date, this link has not been investigated in relation to other
      important life-history traits such as clutch size and body size, or while
      controlling for shared ancestry between species. We provide the first
      phylogenetically based tests using a database with information on egg size,
      clutch size, body size and care duration in cichlid fishes (Cichlidae). Multiple
      regression analyses, based on independent contrasts on both the species and the
      genus level, showed that clutch size is the variable most closely related to
      duration of care. This pattern appeared to be driven by post-hatch care
      relationships. Our results show that, contrary to expectation, there is no
      positive link between egg size and care duration in Cichlidae. Instead, greater
      reproductive output through increased clutch size investment appears to have
      coevolved with greater care of offspring. We suggest that re-evaluation of the
      generality of current models of the evolution of egg size under parental care in
      fishes is needed.

PMID- 16405579
TI  - Life history evolution in cichlids 2: directional evolution of the trade-off
      between egg number and egg size.
AB  - The negative relationship between offspring number and offspring size provides a
      classic example of the role of trade-offs in life history theory. However, the
      evolutionary transitions in egg size and clutch size that have produced this
      negative relationship are still largely unknown. Since body size may affect both
      of these traits, it would be helpful to understand how evolutionary changes in
      body size may have facilitated or constrained shifts in clutch and egg size. By
      using comparative methods with a database of life histories and a phylogeny of
      222 genera of cichlid fishes, we investigated the order of evolutionary
      transitions in these traits in relation to each other. We found that the
      ancestral large-bodied cichlids first increased egg size, followed by a decrease
      in both body size and clutch size resulting in the common current combination of
      a small-bodied cichlid with a small clutch of large eggs. Furthermore, lineages
      that deviated from the negative relationship between clutch and egg size
      underwent different transitions in these traits according to their body size
      (large bodied genera have moved towards the large clutch/small egg end of the
      continuum and small bodied genera towards the small clutch/large egg end of the
      continuum) to reach the negative relationship between clutch size and egg size.
      Our results show that body size is highly important in shaping the negative
      relationship between clutch size and egg size.

PMID- 16405580
TI  - Size asymmetry in intraspecific competition and the density-dependence of
      inbreeding depression in a natural plant population: a case study in cassava
      (Manihot esculenta Crantz, Euphorbiaceae).
AB  - The effects of competition on the genetic composition of natural populations are
      not well understood. We combined demography and molecular genetics to study how
      intraspecific competition affects microevolution in cohorts of volunteer plants
      of cassava (Manihot esculenta) originating from seeds in slash-and-burn fields of
      Palikur Amerindians in French Guiana. In this clonally propagated crop, genotypic
      diversity is enhanced by the incorporation of volunteer plants into farmers'
      stocks of clonal propagules. Mortality of volunteer plants was density-dependent.
      Furthermore, the size asymmetry of intraspecific competition increased with local
      clustering of plants. Size of plants was correlated with their multilocus
      heterozygosity, and stronger size-dependence of survival in clusters of plants,
      compared with solitary plants, increased the magnitude of inbreeding depression
      when competition was severe. The density-dependence of inbreeding depression of
      volunteer plants helps explain the high heterozygosity of volunteers that survive
      to harvest time and thus become candidates for clonal propagation. This effect
      could help favour the maintenance of sex in this 'vegetatively' propagated crop
      plant.

PMID- 16405581
TI  - Temporal dynamics of genotypic diversity reveal strong clonal selection in the
      aphid Myzus persicae.
AB  - Parthenogenetic organisms often harbour substantial genotypic diversity. This
      diversity may be the result of recurrent formations of new clones, or it may be
      maintained by environmental heterogeneity acting on ecological differences among
      clones. In aphids, both processes may be important because obligate and cyclical
      parthenogens can form mixed populations. Using microsatellites, I analysed the
      temporal dynamics of clonal diversity in such a population of the aphid Myzus
      persicae over a 1-year period. The frequency distribution of clonal genotypes was
      very skewed, with many rare and few common clones. The relative frequencies of
      common clones underwent strong and rapid changes indicative of intense clonal
      selection. Differences in their host associations suggest that these shifts may
      partly be caused by changes in the abundance of annual host plants. Other
      selective factors of potential importance are also discussed. New, sexually
      produced genotypes made a minor contribution to clonal diversity, consistent with
      the observed heterozygote excess characteristic of predominantly asexual
      populations in M. persicae.

PMID- 16405582
TI  - Disjunct distributions during glacial and interglacial periods in mountain
      butterflies: Erebia epiphron as an example.
AB  - Over several decades, the distribution patterns and evolution of alpine disjunct
      species has become an increasingly discussed subject. Large scale genetic
      analysis has allowed the resolution of the past range changes and intraspecific
      evolution of many species, in Europe especially of Mediterranean origin. However,
      the phylogeographic structures of species with arctic-alpine disjunct
      distribution patterns are relatively poorly studied. The existing phylogeographic
      analysis (mostly of alpine plant species) supports disjunct distributions during
      glacial as well as post-glacial periods for a number of species. However, several
      questions still remain unresolved and we therefore analysed the Mountain Ringlet
      Erebia epiphron as a model for such alpine disjunct species. We found strong
      differentiation into five different lineages supporting five differentiation
      centres: (i) the eastern Pyrenees, (ii) the mountain ranges between the central
      Pyrenees and south-western Alps, (iii, iv) two areas along the southern Alps
      margin and (v) the northern Alps margin. We propose that these patterns evolved
      due to the humidity requirements of this species, which did not allow survival in
      the dry glacial steppes, but along the margins of the wetter glaciated high
      mountain ranges.

PMID- 16405583
TI  - A comparison of methods to estimate cross-environment genetic correlations.
AB  - Advanced techniques for quantitative genetic parameter estimation may not always
      be necessary to answer broad genetic questions. However, simpler methods are
      often biased, and the extent of this determines their usefulness. In this study
      we compare family mean correlations to least squares and restricted error maximum
      likelihood (REML) variance component approaches to estimating cross-environment
      genetic correlations. We analysed empirical data from studies where both types of
      estimates were made, and from studies in our own laboratories. We found that the
      agreement between estimates was better when full-sib rather than half-sib
      estimates of cross-environment genetic correlations were used and when mean
      family size increased. We also note biases in REML estimation that may be
      especially important when testing to see if correlations differ from 0 or 1. We
      conclude that correlations calculated from family means can be used to test for
      the presence of genetic correlations across environments, which is sufficient for
      some research questions. Variance component approaches should be used when
      parameter estimation is the objective, or if the goal is anything other than
      determining broad patterns.

PMID- 16405584
TI  - Yolk androgens in the barn swallow (Hirundo rustica): a test of some adaptive
      hypotheses.
AB  - Maternal effects such as androgen in avian eggs can mediate evolutionary
      responses to selection, allowing manipulation of offspring phenotype and
      promoting trans-generational adaptive effects. We tested the predictions of two
      adaptive hypotheses that have been proposed to explain female variation in yolk
      androgen allocation in birds, using the barn swallow Hirundo rustica as a model.
      We found no support for the first hypothesis proposing that yolk androgen varies
      as a function of breeding density in order to prepare offspring for different
      breeding densities. However, we found experimental support for the hypothesis
      that female yolk androgen allocation depends on mate attractiveness and that it
      constitutes an example of differential allocation. Females increased the
      concentration of androgens in their eggs when mated to males with experimentally
      elongated tails. Female phenotypic quality as measured by arrival date and clutch
      size was positively related to egg androgen concentration, consistent with the
      hypothesis that this is a costly investment, constrained by female condition. We
      found correlative evidence of a direct relationship between egg androgen
      concentration and performance of offspring as measured by mass increase.

PMID- 16405585
TI  - Does genetic diversity hinder parasite evolution in social insect colonies?
AB  - Polyandry is often difficult to explain because benefits of the behaviour have
      proved elusive. In social insects, polyandry increases the genetic diversity of
      workers within a colony and this has been suggested to improve the resistance of
      the colony to disease. Here we examine the possible impact of host genetic
      diversity on parasite evolution by carrying out serial passages of a virulent
      fungal pathogen through leaf-cutting ant workers of known genotypes. Parasite
      virulence increased over the nine-generation span of the experiment while spore
      production decreased. The effect of host relatedness upon virulence appeared
      limited. However, parasites cycled through more genetically diverse hosts were
      more likely to go extinct during the experiment and parasites cycled through more
      genetically similar hosts had greater spore production. These results indicate
      that host genetic diversity may indeed hinder the ability of parasites to adapt
      while cycling within social insect colonies.

PMID- 16405586
TI  - Fitness consequences of variable maternal provisioning in quacking frogs (Crinia
      georgiana).
AB  - Variable maternal provisioning may evolve when there is variation in the quality
      of offspring environments. The frog Crinia georgiana has high variability in egg
      size both within and between clutches, independent of female phenotype. It breeds
      in ponds with high spatial and temporal variation in habitat quality. Egg size
      strongly affected offspring fitness in good and poor quality offspring
      environments, whether the egg size difference was from between or within
      clutches. Since there is a trade-off in egg size and number, these fitness
      consequences translate to strong effects on maternal fitness. In the variable and
      unpredictable offspring environment of C. georgiana, the maintenance of variable
      maternal provisioning both within and between clutches is likely to be an evolved
      response to the offspring environment.

PMID- 16405587
TI  - Cophylogenetic relationships between penguins and their chewing lice.
AB  - It is generally thought that the evolution of obligate parasites should be linked
      intimately to the evolution of their hosts and that speciation by the hosts
      should cause speciation of their parasites. The penguins and their chewing lice
      present a rare opportunity to examine codivergence between a complete host order
      and its parasitic lice. We estimated a phylogeny for all 15 species of lice
      parasitising all 17 species of penguins from the third domain of the
      mitochondrial 12S ribosomal rRNA gene, a portion of the mitochondrial cytochrome
      oxidase subunit 1 gene and 55 morphological characters. We found no evidence of
      extensive cospeciation between penguins and their chewing lice using TreeMap
      2.02beta. Despite the paucity of cospeciation, there is support for significant
      congruence between the louse and penguin phylogenies due to possible failure to
      speciate events (parasites not speciating in response to their hosts speciating).

PMID- 16405588
TI  - Analysis of microsatellite variation in Pinus radiata reveals effects of genetic
      drift but no recent bottlenecks.
AB  - Most conifer species occur in large continuous populations, but radiata pine,
      Pinus radiata, occurs only in five disjunctive natural populations in California
      and Mexico. The Mexican island populations were presumably colonized from the
      mainland millions of years ago. According to Axelrod (1981), the mainland
      populations are relicts of an earlier much wider distribution, reduced some 8,000
      years ago, whereas according to Millar (1997, 2000), the patchy metapopulation
      like structure is typical of the long-term population demography of the species.
      We used 19 highly polymorphic microsatellite loci to describe population
      structure and to search for signs of the dynamics of population demography over
      space and time. Frequencies of null alleles at microsatellite loci were estimated
      using an approach based on the probability of identity by descent. Microsatellite
      genetic diversities were high in all populations [expected heterozygosity (H(e))
      = 0.68-0.77], but the island populations had significantly lower estimates.
      Variation between loci in genetic differentiation (F(ST)) was high, but no locus
      deviated statistically significantly from the rest at an experiment wide level of
      0.05. Thus, all loci were included in subsequent analysis. The average
      differentiation was measured as F(ST) = 0.14 (SD 0.012), comparable with earlier
      allozyme results. The island populations were more diverged from the other
      populations and from an inferred common ancestral gene pool than the mainland
      ones. All populations showed a deficiency of expected heterozygosity given the
      number of alleles, the mainland populations more so than the island ones. The
      results thus do not support a recent important contraction in the mainland range
      of radiata pine.

PMID- 16405589
TI  - An experimental test of the causes of small-scale phenotypic differentiation in a
      population of great tits.
AB  - Phenotypic differentiation between populations is thought to occur mainly at
      spatial scales where gene-flow is restricted and selection regimes differ.
      However, if gene flow is nonrandom, dispersal may reinforce, rather than
      counteract, evolutionary differentiation, meaning that differences occurring over
      small scales might have a genetic basis. The purpose of this study was to
      determine the cause of differences in mean phenotype between two parts of a
      population of great tits Parus major, separated by <3 km. We conducted a partial
      cross-fostering experiment between two contrasting parts of this population to
      separate genetic and environmental sources of variation, and to test for gene
      environment interaction. We found strong environmental effects on nestling size,
      mass and condition index, with nestlings reared in a low density part of the
      population being larger, heavier and in better condition, than those in a high
      density part, irrespective of their origin. In addition, we found smaller, but
      significant, differences in nestling condition and shape associated with the
      areas that birds originated from, suggesting the presence of genetic differences
      between parts of this population. There was no evidence of gene-environment
      interaction for any character. This experiment is thus consistent with previous
      analyses suggesting that differences between parts of this population had evolved
      recently, apparently due to phenotype-dependent dispersal, and indicates that
      population differentiation can be maintained over small spatial scales despite
      extensive dispersal.

PMID- 16405590
TI  - No evidence for the 'Meselson effect' in parthenogenetic oribatid mites
      (Oribatida, Acari).
AB  - It has been hypothesized that in ancient apomictic, nonrecombining lineages the
      two alleles of a single copy gene will become highly divergent as a result of the
      independent accumulation of mutations (Meselson effect). We used a partial
      sequence of the elongation factor-1alpha (ef-1alpha) and the heat shock protein
      82 (hsp82) genes to test this hypothesis for putative ancient parthenogenetic
      oribatid mite lineages. In addition, we tested if the hsp82 gene is fully
      transcribed by sequencing the cDNA and we also tested if there is evidence for
      recombination and gene conversion in sexual and parthenogenetic oribatid mite
      species. The average maximum intra-specific divergence in the ef-1alpha was 2.7%
      in three parthenogenetic species and 8.6% in three sexual species; the average
      maximum intra-individual genetic divergence was 0.9% in the parthenogenetic and
      6.0% in the sexual species. In the hsp82 gene the average maximum intra
      individual genetic divergence in the sexual species Steganacarus magnus and in
      the parthenogenetic species Platynothrus peltifer was 1.1% and 1.2%,
      respectively. None of the differences were statistically significant. The cDNA
      data indicated that the hsp82 sequence is transcribed and intron-free. Likelihood
      permutation tests indicate that ef-1alpha has undergone recombination in all
      three studied sexual species and gene conversion in two of the sexual species,
      but neither process has occurred in any of the parthenogenetic species. No
      evidence for recombination or gene conversion was found for sexual or
      parthenogenetic oribatid mite species in the hsp 82 gene. There appears to be no
      Meselson effect in parthenogenetic oribatid mite species. Presumably, their low
      genetic divergence is due to automixis, other homogenizing mechanisms or strong
      selection to keep both the ef-1alpha and the hsp82 gene functioning.

PMID- 16405591
TI  - Can maternally transmitted endosymbionts facilitate the evolution of
      haplodiploidy?
AB  - Whilst many invertebrate taxa are haplodiploid, the factors underlying the
      evolution of haplodiploidy remain unresolved. We investigate theoretically
      whether haplodiploidy might evolve as an outcome of the co-evolution between
      maternally inherited endosymbionts and their hosts. First, we substantially
      extend a recently developed model that involves maternally inherited
      endosymbionts that kill male offspring by eliminating the paternal genome. We
      also put forward a new hypothesis and develop a model that involves bacteria that
      induce cytoplasmic incompatibility (CI). Based on these models, we explore the co
      evolutionary events that might occur between hosts and symbionts. We find that
      both with male-killers and CI-inducing endosymbionts, the hosts are likely to
      develop increased viability of haploid males, which can be considered a
      preadaptation to haplodiploidy. In addition, populations with haploidizing male
      killers can in some cases evolve directly towards a genetic system of paternal
      genome elimination, a special form of haplodiploidy. These results are combined
      with consideration of mechanism and ecology to appraise the likelihood of male
      killers and CI inducing bacteria being involved in the evolution of
      haplodiploidy.

PMID- 16405592
TI  - Geographical patterns of adaptation within a species' range: interactions between
      drift and gene flow.
AB  - We use individual-based stochastic simulations and analytical deterministic
      predictions to investigate the interaction between drift, natural selection and
      gene flow on the patterns of local adaptation across a fragmented species' range
      under clinally varying selection. Migration between populations follows a
      stepping-stone pattern and density decreases from the centre to the periphery of
      the range. Increased migration worsens gene swamping in small marginal
      populations but mitigates the effect of drift by replenishing genetic variance
      and helping purge deleterious mutations. Contrary to the deterministic prediction
      that increased connectivity within the range always inhibits local adaptation,
      simulations show that low intermediate migration rates improve fitness in
      marginal populations and attenuate fitness heterogeneity across the range. Such
      migration rates are optimal in that they maximize the total mean fitness at the
      scale of the range. Optimal migration rates increase with shallower environmental
      gradients, smaller marginal populations and higher mutation rates affecting
      fitness.

PMID- 16405593
TI  - Changes in genetic architecture during relaxation in Drosophila melanogaster
      selected on divergent virgin life span.
AB  - Artificial selection experiments often confer important information on the
      genetic correlations constraining the evolution of life history. After artificial
      selection has ceased however, selection pressures in the culture environment can
      change the correlation matrix again. Here, we reinvestigate direct and correlated
      responses in a set of lines of Drosophila melanogaster that were selected on
      virgin life span and for which selection has been relaxed for 10 years. The
      decrease in progeny production in long-lived lines, a strong indication of
      antagonistic pleiotropy, had disappeared during relaxation. This was associated
      with a higher cost of reproduction to long-lived flies in mated, but not in
      virgin life span. These data strongly suggest that genetic mechanisms of mated
      and virgin life span determination are partly independent. Furthermore, data on
      body weight, developmental time and viability indicated deleterious effects of
      longevity selection in either direction, giving rise to a nonlinear relationship
      with life span for these characters. In order to reclaim original patterns, we
      founded a new set of derived lines by resuming selection in mixed replicate lines
      of the original set. Although selection was successful, most patterns in
      correlated characters remained, showing that these new patterns are resistant to
      new episodes of selection.

PMID- 16405594
TI  - Rapid temporal change in the expression and age-related information content of a
      sexually selected trait.
AB  - The expression of sexual signals is often phenotypically plastic and also evolves
      rapidly. Few studies have considered the possibility that proximate determination
      -- the pathway between genes and trait expression -- may also be subject to both
      phenotypic plasticity and evolutionary change. We examined long-term patterns in
      size, condition- and age-dependence, repeatability and heritability of forehead
      patch size, a sexually selected plumage trait in male collared flycatchers. We
      also estimated survival and sexual selection on the phenotypic value of the
      trait. Forehead patch size linearly declined during the 15 years, probably due to
      the significantly negative survival selection. In addition, the expression of
      genetic variation for the ornament apparently underwent an age-limited change,
      which implies a change in the information content of the signal to receivers. The
      persistent lack of condition-dependence makes phenotypic plasticity an unlikely
      explanation to our results. This raises the possibility of a microevolutionary
      change of both expression and proximate determination during the study period.

PMID- 16405595
TI  - Contrasting genetic structures across two hybrid zones of a tropical reef fish,
      Acanthochromis polyacanthus (Bleeker 1855).
AB  - Hybrid zones are natural laboratories offering insights into speciation
      processes. Narrow hybrid zones are less common in the sea than on land consistent
      with higher dispersal among marine populations. Acanthochromis polyacanthus is an
      unusual bony marine fish with philopatric dispersal that exists as allopatric
      stocks of white, bicoloured and black fish on the Great Barrier Reef (GBR). At
      two latitudes, different morphs coexist and hybridize at narrow contact zones.
      Sequence data from mitochondrial Hypervariable Region 1 revealed contrasting
      patterns of introgression across these zones. At the northern hybrid zone, a
      single clade of mitochondrial haplotypes was found in all white fish, hybrids and
      tens of kilometres into pure bicoloured stock. At the southern hybrid zone, there
      was no introgression of mitochondrial genes into black fish and hybrids shared
      the bicoloured haplotypes. Based on this asymmetry, we postulate that black fish
      from the southern GBR have experienced a selective sweep of their mitochondrial
      genome, which has resulted in almost total reproductive isolation.

PMID- 16405596
TI  - Patterns of diversification of Afrotropical Otiteselline fig wasps: phylogenetic
      study reveals a double radiation across host figs and conservatism of host
      association.
AB  - We studied the phylogenetic relationships of Otiteselline fig waSPS associated
      with Ficus in the Afrotropical region using rDNA sequences. African fig species
      usually host two species of Otiteselline fig waSPS. Phylogenetic analyses reveal
      that this pattern of association results from the radiation of two clades of
      waSPS superimposed on the fig system. Within each clade, wasp species generally
      cluster according to their host classification. The phylogenies of the two clades
      are also generally more congruent than expected by chance. Together these results
      suggest that Otiteselline wasp speciation is largely constrained by the
      diversification of their hosts. Finally, we show a difference in ovipositor
      length between the two Otiteselline species coexisting in the same Ficus species,
      which probably corresponds to ecological differences. The diversification of
      ecological niches within the fig is probably, with cospeciation, one of the key
      factors explaining the diversification and maintenance of species of parasites of
      the fig/pollinator system.

PMID- 16405597
TI  - Why does a grasshopper have fewer, larger offspring at its range limits?
AB  - Analysis of size of offspring reared through three laboratory generations from
      populations of the field grasshopper Chorthippus brunneus from 27 sites around
      the British Isles showed that offspring were larger towards the cooler-wetter
      conditions in the western and northern limits of the range. This variation had a
      significant genetic component. There was a trade-off between clutch size and
      offspring size between and within populations. Under favourable thermal and
      feeding conditions maternal fitness was optimal when individuals produced the
      largest clutches of the smallest eggs, but under poor conditions maternal fitness
      was optimal when individuals produced small clutches of very large offspring.
      Calculation of geometric mean fitness over time indicated that having larger
      offspring near to the edge of the range could be advantageous as a conservative
      risk-spreading strategy. As well as geographic variation in egg size, significant
      environment-genotype interactions in egg size in relation to temperature were
      observed.

PMID- 16405598
TI  - Host resistance and parasite virulence in greenfinch coccidiosis.
AB  - The question why different host individuals within a population differ with
      respect to infection resistance is of fundamental importance for understanding
      the mechanisms of parasite-mediated selection. We addressed this question by
      infecting wild-caught captive male greenfinches with intestinal coccidian
      parasites originating either from single or multiple hosts. Birds with naturally
      low pre-experimental infection retained their low infection status also after
      reinfection with multiple strains, indicating that natural infection intensities
      confer information about the phenotypic ability of individuals to resist novel
      strains. Exposure to novel strains did not result in protective immunity against
      the subsequent infection with the same strains. Infection with multiple strains
      resulted in greater virulence than single-strain infection, indicating that
      parasites originating from different host individuals are genetically diverse.
      Our experiment thus demonstrates the validity of important but rarely tested
      assumptions of many models of parasite-mediated selection in a wild bird species
      and its common parasite.

PMID- 16405599
TI  - Evolution of late-life fecundity in Drosophila melanogaster.
AB  - Late-life fecundity has been shown to plateau at late ages in Drosophila
      analogously to late-life mortality rates. In this study, we test an evolutionary
      theory of late life based on the declining force of natural selection that can
      explain the occurrence of these late-life plateaus in Drosophila. We also examine
      the viability of eggs laid by late-age females and test a population genetic
      mechanism that may be involved in the evolution of late-life fecundity:
      antagonistic pleiotropy. Together these experiments demonstrate that (i)
      fecundity plateaus at late ages, (ii) plateaus evolve according to the age at
      which the force of natural selection acting on fecundity reaches zero, (iii) eggs
      laid by females in late life are viable and (iv) antagonistic pleiotropy is
      involved in the evolution of late-life fecundity. This study further supports the
      evolutionary theory of late life based on the age-specific force of natural
      selection.

PMID- 16405600
TI  - The influence of environmental factors, the pollen : ovule ratio and seed bank
      persistence on molecular evolutionary rates in plants.
AB  - One of the main goals of molecular evolutionary biology is to determine the
      factors that influence the evolutionary rate of selectively neutral DNA, but much
      remains unknown, especially for plants. Key factors that could alter the mutation
      rate include environmental tolerances (because they reflect a plants
      vulnerability to changes in habitat), the pollen:ovule ratio (as it is associated
      with the number of mitotic divisions) and seed longevity (because this influences
      the number of generations per unit time in plants). This is the first study to
      demonstrate that seed bank persistence and drought tolerance are positively
      associated with molecular evolutionary rates in plants and that pollen:ovule
      ratio, shade tolerance and salinity tolerance have no detectable relationship.
      The implications of the findings to our understanding of the impact of
      environmental agents, the number of cell divisions and cell aging on neutral DNA
      sequence evolution are discussed.

PMID- 16405601
TI  - Psychosocial effects of vitiligo.
AB  - A limited number of studies have paid attention to the psychosocial well-being of
      patients affected with vitiligo. We review the psychosocial effects of vitiligo,
      how patients deal with them and the psychiatric morbidity in vitiligo patients.
      Given the appreciable comorbidity, it is important to consider these observations
      in the management of patients, for example in patient-physician interaction but
      also in treatment strategies and evaluation of treatments. The effects of the
      psychological state on the disease itself together with the potential therapeutic
      implications are reviewed. Based on these data, we suggest how to further improve
      patient's management.

PMID- 16405602
TI  - Evidence-based review of hair removal using lasers and light sources.
AB  - BACKGROUND: Unwanted hair growth remains a therapeutic challenge and there is a
      considerable need for an effective and safe treatment modality. OBJECTIVE: From
      an evidence-based view to summarize efficacy and adverse effects from hair
      removal with ruby, alexandrite, diode, and Nd:YAG lasers and intense pulsed light
      (IPL). METHODS: Original publications of controlled clinical trials were
      identified in Medline and the Cochrane Library. RESULTS: A total of 9 randomized
      controlled (RCTs) and 21 controlled trials (CTs) were identified. The best
      available evidence was found for the alexandrite (three RCTs, eight CTs) and
      diode (three RCTs, four CTs) lasers, followed by the ruby (two RCTs, six CTs) and
      Nd:YAG (two RCTs, four CTs) lasers, whereas limited evidence was available for
      IPL sources (one RCT, one CT). Based on the present best available evidence we
      conclude that (i) epilation with lasers and light sources induces a partial short
      term hair reduction up to 6 months postoperatively, (ii) efficacy is improved
      when repeated treatments are given, (iii) efficacy is superior to conventional
      treatments (shaving, wax epilation, electrolysis), (iv) evidence exists for a
      partial long-term hair removal efficacy beyond 6 months postoperatively after
      repetitive treatments with alexandrite and diode lasers and probably after
      treatment with ruby and Nd:YAG lasers, whereas evidence is lacking for long-term
      hair removal after IPL treatment, (v) today there is no evidence for a complete
      and persistent hair removal efficacy, (vi) the occurrence of postoperative side
      effects is reported low for all the laser systems. CONCLUSION: The evidence from
      controlled clinical trials favours the use of lasers and light sources for
      removal of unwanted hair. We recommend that patients are pre-operatively informed
      of the expected treatment outcome.

PMID- 16405603
TI  - Correlation between HLA and pityriasis rosea susceptibility in Brazilian blacks.
AB  - OBJECTIVES: The human leucocyte antigen (HLA) has been related to susceptibility
      factors in several diseases. This study aimed to determine the potential genetic
      susceptibility of patients with pityriasis rosea (PR) through HLA molecular
      typing analysis. METHODS: The method of choice was polymerase chain reaction with
      sequence-specific primers (PCR-SSP) using low-resolution typing kits, with
      determination of the alleles class I (HLA-A, HLA-B and HLA-C) and class II (HLA
      DRB1, DRB3, DRB4, DRB5 and DQB1) performed in 30 Afro-Brazilian PR-diagnosed
      patients and 45 healthy individuals as the control group (PR-C). RESULTS:
      Analysis of the HLA typing results showed that the relative risk (RR) of 4.00
      [95% confidence interval (95% CI) 1.20-13.28, two-tailed P = 0.018] for allele
      HLA-DQB1*04 class II, detected in 33.3% of PR patients, was significant. By
      contrast, in the control group only 11.1% of subjects had that allele. Three out
      of six B*51 alleles and three out of six B*53 alleles detected in PR patients
      were found, together with the allele DQB1*04. CONCLUSION: We suggest that alleles
      DQB1*04 may be involved in the genetic susceptibility of PR based on the
      significant predominance of those alleles observed in the black PR patients. We
      also recommend that more studies are conducted on populations of other ethnic
      origins, preferentially with higher resolution techniques of DNA typing.

PMID- 16405604
TI  - Effect of calcipotriol on epidermal cell populations in alefacept-treated
      psoriatic lesions.
AB  - BACKGROUND AND OBJECTIVES: The effect of the established antipsoriatic treatment
      with topical calcipotriol (with a maximum of 100 g per week) in addition to
      systemic treatment with alefacept, a new biological agent for psoriasis, on
      epidermal cell populations in the psoriatic lesion was investigated using a
      combination of the Zenon labelling technique and microscopic image analysis.
      Epidermal cell populations were measured quantitatively with this sensitive
      method. PATIENTS/METHODS: Frozen sections of non-treated psoriatic epidermis and
      psoriatic epidermis treated with either alefacept intramuscular or alefacept
      intramuscular in combination with topical calcipotriol for 12 weeks were compared
      immunohistochemically. Antibodies against keratin 6, 10 and 15 were labelled with
      the Zenon technique, whereas antibodies against the Ki-67 antigen and beta-1
      integrin were covalently Fluorescein Isothiocyanate (FITC)-labelled. Using image
      analysis, these markers were measured in the epidermis in a standardized manner.
      RESULTS AND CONCLUSIONS: Treatment of psoriasis with alefacept resulted in a good
      clinical response in several patients and in a normalization of epidermal
      expression of the immunohistochemical parameters for differentiation and
      proliferation. The addition of topical calcipotriol resulted in a faster clinical
      improvement with a similar overall clinical response and a similar response of
      epidermal cell populations as compared to treatment with alefacept monotherapy
      after 12 weeks of treatment. This study also suggests that the appearance of
      keratin 15 has a predictive value for the duration of remission. It can be
      concluded that the addition of a low-dose calcipotriol treatment does not
      contribute to the clinical efficacy of alefacept, both at the clinical level and
      with respect to markers for epidermal proliferation and differentiation.

PMID- 16405605
TI  - Colorimetric analysis of pigmented skin lesions: a pilot study with the Visi
      Chroma VC-100 device.
AB  - BACKGROUND: Definition of the colour of pigmented skin lesions (PSLs) with the
      naked eye remains subjective and may be influenced by lighting. This problem
      underlines the usefulness of instrumental assessments such as epiluminescence
      microscopy and colorimetric devices. OBJECTIVE AND METHODS: We describe here a
      new method of colour analysis of PSLs with the Visi-Chroma VC-100 device, which
      illuminates the surface of the skin with white light-emitting diodes (LEDs) and
      analyses the reflected light by a red-green-blue (RGB) charge-coupled device
      (CCD) colour camera. Twenty-one PSLs to be excised for cosmetic or medical
      reasons were analysed by this device with clinicopathological correlation.
      CONCLUSIONS: This method is feasible and might be useful to assess the colour of
      PSLs and allow comparisons for changes over time. Further studies are needed to
      determine the usefulness of this device in clinical practice.

PMID- 16405606
TI  - Consistency of data in six phase III clinical studies of a two-compound product
      containing calcipotriol and betamethasone dipropionate ointment for the treatment
      of psoriasis.
AB  - BACKGROUND: Calcipotriol and betamethasone dipropionate are both proven products
      in the topical treatment of psoriasis. The efficacy and tolerability of a new
      ointment containing these two compounds has been assessed in six phase III
      clinical studies. OBJECTIVE: To compare the results obtained in the clinical
      studies of the new calcipotriol/betamethasone dipropionate ointment. METHODS: A
      total of 6050 patients with psoriasis took part in the six randomized, double
      blind studies. The two-compound product was compared with each of the active
      constituents, either in the new ointment vehicle or in the marketed formulation.
      RESULTS: After 4 weeks of treatment the mean reduction in the Psoriasis Area and
      Severity Index (PASI) ranged from 65 to 74% with the two-compound product applied
      once or twice daily, from 46 to 59% with calcipotriol alone and from 57 to 63%
      with betamethasone dipropionate alone. The tolerability profile of the two
      compound product was similar to betamethasone dipropionate monotherapy and better
      than calcipotriol alone. CONCLUSION: The new two-compound product containing
      calcipotriol and betamethasone dipropionate was found to consistently provide
      rapid, highly effective treatment of psoriasis vulgaris.

PMID- 16405608
TI  - Correlation between Bcl-2 and Bax in atrophic and hypertrophic type of actinic
      keratosis.
AB  - BACKGROUND: Recent investigations consider actinic keratosis (AK) as an earliest
      visible pattern of squamous cell carcinoma (SCC). We have analysed the expression
      of apoptosis-related proteins TP53, Bcl-2 and Bax in 30 atrophic and 30
      hypertrophic AK cases. MATERIAL AND METHODS: Immunohistochemical analysis was
      performed following microwave streptavidin immunoperoxidase protocol on DAKO
      TechMate Horizon automated immunostainer (DAKO, Copenhagen, Denmark). Monoclonal
      antibody for TP53 and Bcl-2 and polyclonal antibody for Bax (DAKO, Copenhagen,
      Denmark) were used. RESULTS: Expression of TP53 showed no significant differences
      between two analysed groups (chi2-test, P = 0.35636) whereas expression of Bcl-2
      and Bax protein was significantly higher in atrophic compared to hypertrophic AK
      (chi2-test, P = 0.01458 and P = 0.00358, respectively). Comparison of Bcl-2 : Bax
      ratio in two analysed AK showed significantly higher value in hypertrophic
      compared to atrophic AK (Mann-Whitney U test, P = 0.02272). Statistical analysis
      did not show any correlation between patient's sex and age, localization and size
      of the lesion with expression of investigated oncoproteins (anova, P > 0.05).
      CONCLUSIONS: Our results may indicate higher resistance of keratinocytes on
      apoptotic stimuli in hypertrophic compared to atrophic AK. Thus, we suppose that
      keratinocytes in hypertrophic AK live longer and probably have higher propensity
      for additional mutations and conversion to overt SCC.

PMID- 16405607
TI  - Quality of life and acne in Scottish adolescent schoolchildren: use of the
      Children's Dermatology Life Quality Index (CDLQI) and the Cardiff Acne Disability
      Index (CADI).
AB  - BACKGROUND: Acne vulgaris is known to adversely affect all aspects of quality of
      life. However, although acne is thought to occur in the majority of adolescents,
      there are few data currently available on the impact of acne in this age group.
      OBJECTIVES: Measurement of the impairment of health-related quality of life
      (HRQoL) in teenage Scottish schoolchildren in a comparative study using two HRQoL
      questionnaires. A secondary objective was to collect data on the use and
      perceived efficacy of medical and over-the-counter (OTC) preparations. STUDY
      DESIGN: An anonymous cross-sectional survey of 200 adolescent (15-18 years)
      Dundee schoolchildren was conducted by means of two self-reported questionnaires:
      the Children's Dermatology Life Quality Index (CDLQI) and the Cardiff Acne
      Disability Index (CADI). Data on demographics and therapeutic modalities and
      their perceived efficacy were also collected. ANALYSIS: Statistical analysis was
      performed using the package Stata 7.0. RESULTS: Self-reported acne was present in
      83% of teenagers (147/178), with similar sex distribution (54% male, 46% female).
      The overall mean CDLQI score (max. 30) was low 1.7 {6% impairment} (CI -1 to 0),
      range 0-19. Nine pupils scored between 5 and 9 {17-30% impairment} suggesting
      moderate HRQoL impairment and three scored > 10 {> 33% impairment} indicating
      severe impairment. The overall mean CADI score (max. 15) of 1.9 {13% impairment},
      CI 0 to 1 (range 0-15) was also low, but 12 pupils scored between 5 and 9 {33-60%
      impairment}, one scoring 10 + {> 67% impairment} and one scoring the maximum, 15
      {100% impairment}. There was no significant difference in mean scores between the
      sexes in either questionnaire (P = 0.5). There was good correlation between the
      results from the two questionnaires (Spearman's rho = 0.62). Three-quarters (75%)
      had used OTC products, of which only a third (33%) felt they helped 'a lot'.
      Fifteen per cent were receiving prescribed treatment from their doctors of which
      66% found it helpful. CONCLUSIONS: Self-reported acne occurred in 83% (147/178)
      of the Scottish teenagers involved in this study, which confirms previous reports
      of a high prevalence of acne in teenagers. Cross-validation of the CLDQI and CADI
      demonstrated good correlation and both scales were easy to administer and
      identified 11% (16/147) of teenagers who perceive their lives to be significantly
      affected by their acne (8% moderately to severely, 3% severely). It is important
      to identify and treat such teenagers early to reduce the future socio-economic
      burden of their acne.

PMID- 16405609
TI  - Evaluation of patients with symptomatic dermographism.
AB  - BACKGROUND: Dermographism or 'simple' dermographism, which has been noted in
      about 1.5% to 5% of healthy individuals, is regarded as a normal physiological
      phenomenon. However, in symptomatic dermographism (SD), even light pressure or
      rubbing from clothes may provoke widespread weal-and-flare reactions with itching
      and burning. It is one of the dermatologic diseases that negatively impacts
      quality of life. OBJECTIVE: We aimed to reveal triggering factors and/or
      associated clinical conditions in patients with SD. METHODS: Forty patients (28
      women and 12 men) with SD whose ages varied between 7 and 65 (30.3 +/- 10.7)
      participated in the study. Patients having chronic idiopathic urticaria, other
      types of physical urticaria and cutaneous/systemic mastocytosis were excluded.
      The diagnosis of SD was confirmed by stroking the skin of the back with a tongue
      blade. This procedure elicited within minutes a linear weal with a flare and
      severe itching. In light of the history, physical examination, skin prick test
      (SPT) with aeroallergens and laboratory results, a possible relationship of
      certain triggering factors and/or associated diseases (psychic factors, atopy,
      thyroid diseases, diabetes, menopause, infectious, systemic or malignant
      diseases, history of scabies, and history of drug reaction) to SD were
      investigated. RESULTS: The duration of SD varied between 10 days and 10 years
      (mean: 20.8 months). Psychic factors were found to play the initial triggering
      role in 12 patients (30%). Five patients (12.50%) were atopic, and they had SPT
      reactivity to house dust mites. Three female patients (7.50%) defined that their
      complaints began following drug-induced urticarial rash. Two patients (5%) had
      hyperthyroidism, and one of the patients with SD of 1-month duration had type-II
      diabetes mellitus. A female patient defined that her complaints began during the
      onset of menopausal period. SD was observed with scabies in one patient; and
      after poststreptococcal glomerulonephritis in a 7-year-old girl. No autoimmune,
      malignant or other systemic diseases were found in patients with SD. CONCLUSIONS:
      Contrary to commonly held opinion, SD may be associated with some diseases and/or
      triggered by some conditions. In this study, a close temporal relationship
      between the appearance of SD and psychic factors, drug reactions and scabies was
      documented. The relation between SD and atopy, hyperthyroidism, diabetes
      mellitus, menopause and glomerulonephritis seemed unclear.

PMID- 16405610
TI  - Simultaneous occurrence of linear scleroderma and homolateral segmental vitiligo.
AB  - Localized scleroderma and vitiligo only rarely have been reported to occur
      simultaneously. Here we report a case of a 21 year old man affected with both
      linear scleroderma of the left upper limb and homolateral segmental vitiligo of
      the trunk. Since the two diseases appeared during the same period, involved the
      same side of the body and their progression paralleled, a possible non
      coincidental association between these two diseases is discussed.

PMID- 16405611
TI  - Successful treatment of severe recalcitrant erosive oral lichen planus with
      topical tacrolimus.
AB  - Oral lichen planus (LP) is a severe, painful form of LP, and is often resistant
      to topical corticosteroid therapy. Recently, open trials demonstrated that
      topical tacrolimus therapy was effective for the treatment of chronic erosive
      oral LP. We report two cases with severe recalcitrant erosive oral LP, who
      dramatically benefited from topical tacrolimus therapy. In case 1, a 64-year-old
      man presented with a 5-month history of painful erosions on his entire lower lip
      and buccal mucosa. Physical and histological examination confirmed a diagnosis of
      LP. He experienced rapid relief from pain and a dramatic improvement was obtained
      within 5 weeks of topical tacrolimus treatment. No significant irritation was
      observed and blood tacrolimus level was kept within a safe level (2.5 ng/mL). In
      case 2, a 68-year-old man developed painful erosions on his right lower lip and
      buccal mucosa 2 months before his arrival at our hospital. Histopathological
      analysis confirmed a diagnosis of oral LP. He experienced a rapid dramatic
      improvement of both lesions within 4 weeks of the start of tacrolimus
      application. No significant irritation or recurrence was observed. Thus, topical
      tacrolimus is suggested as a well-tolerated, effective therapy for oral LP.

PMID- 16405612
TI  - Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of
      literature.
AB  - Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease with poor
      prognosis when associated with malignant neoplasm. We report the case of a
      patient with PNP associated with a CD20+ non-Hodgkin follicular lymphoma who was
      treated with Rituximab plus corticosteroids and short courses of cyclosporin. One
      and a half years after Rituximab therapy, oral ulcerations had cleared and oral
      methylprednisolone was slowly tapered down without further recurrences. In the
      course of the disease, the patient developed sepsis due to Listeria monocytogenes
      and viral infections by human herpes virus 1 and 3. At the end-stage of the
      disease she developed a cutaneous infection from Mycobacterium chelonae. The
      patient died 2 years and 7 months after the onset of PNP. Rituximab may be useful
      for PNP therapy, but further studies are necessary to confirm this hypothesis.

PMID- 16405613
TI  - Foreign body post-varicella granulomas due to talc.
AB  - Foreign body granulomas in the skin have been described frequently and may have
      various causes. Diagnosis is relatively easy in most cases, as most are related
      to foreign material penetrating into the skin due to different kinds of traumas.
      We present the case of a boy with multiple facial granulomas, persisting more
      than 6 months and related to the use of topical anti-pruriginous talc powder
      applied to papuloexudative lesions caused by varicella. Data gathered in the
      anamnesis, examination with polarized light and images seen through the electron
      microscope enabled us to identify the causal agent talc as the inducer of the
      granulomatous lesions that the patient presented, discarding other types of
      foreign body granulomas of exogenous origin.

PMID- 16405614
TI  - Localized Kaposi's sarcoma in a patient with pemphigus vulgaris.
AB  - We report the case of a patient with a 13-year history of pemphigus vulgaris (PV)
      treated with immunosuppressive agents, prednisone and mycophenolate mofetil who
      had developed lesions of Kaposi's sarcoma (KS) on a sole plaque of PV that had
      been previously treated with intralesional injections of steroids. The lesions
      were surgically removed and polymerase chain reaction (PCR) demonstrated human
      herpesvirus-8 (HHV-8) DNA. There were neither recurrences nor later dissemination
      of KS following gradual decrease of the immunosuppressive therapy. We suggest
      that the treatment with intralesional steroids may have influenced the local
      reactivation of a latent infection of the virus, determining the appearance of
      this localized KS.

PMID- 16405615
TI  - A case of Darier's disease successfully treated with topical tacrolimus.
AB  - Tacrolimus is a macrolide that inhibits T-cell activation. The most extensive
      experience with topical tacrolimus has been in treating atopic dermatitis but it
      has been used in various skin diseases, including Hailey-Hailey disease, with
      encouraging results. We report a case of extensive Darier's disease successfully
      treated with topical tacrolimus, after suspension of oral isotretrinoin due to
      major depression.

PMID- 16405617
TI  - Familial eruptive dermatofibromas in atopic dermatitis.
AB  - Multiple eruptive dermatofibromas (MEDF) are rare and their aetiology is unknown.
      More than half of the patients with MEDF have underlying diseases, and more than
      80% of the underlying diseases are immune mediated. Familial cases suggesting a
      genetic cause have also been reported. We report a case of familial eruptive
      dermatofibromas associated with atopic dermatitis, possibly caused by both
      hereditary factors and compromised immunity.

PMID- 16405616
TI  - Giant cutaneous rhinosporidiosis.
AB  - A young male with a single, huge subcutaneous lesion of rhinosporidiosis is
      reported. The diagnosis was suggested by the presence of nasal rhinosporidiosis
      and confirmed by fine-needle aspiration cytology (FNAC) from the skin lesion.
      This is the second report of giant skin lesions in rhinosporidiosis, from our
      department.

PMID- 16405618
TI  - Recurrent herpes labialis during isotretinoin therapy: is there a role for
      photosensitivity?
AB  - Isotretinoin (13-cis-retinoic acid) is one of the synthetic retinoids derived
      from vitamin A. Vitamin A derivatives demonstrate virucidal activity, both in
      vivo and in vitro. Isotretinoin has been used for the treatment of recurrent
      herpes simplex with encouraging results. However, we present a case with frequent
      attacks of herpes labialis during isotretinoin therapy for acne, who had a marked
      decrease in frequency of recurrences following strict use of sunscreens.

PMID- 16405619
TI  - Chronic venous insufficiency - a potential trigger for localized scleroderma.
AB  - Localized scleroderma is a cutaneous disease that is characterized by an initial
      inflammatory response, followed by sclerosis of the skin. The cause of localized
      scleroderma has not yet been determined. Seifarth et al. reported two cases of
      localized scleroderma at sites of chronic venous insufficiency. We document here
      three more patients in whom localized scleroderma was located at insufficient
      veins. Treatment of underlying chronic venous insufficiency (CVI) leads to a
      substantial clinical improvement of scleroderma at the site of insufficient
      veins, but not elsewhere. Experimental data support the concept of chronic venous
      insufficiency creating a microenvironment, which may lead to localized
      scleroderma. Local hypoxaemia, which is present in CVI, induces the release of
      endothelium-derived cytokines, such as IL-1. Subsequently, expression of
      endothelial adhesion molecules and consequently leucocyte extravasation are
      induced. Infiltrating leucocytes secrete a number of inflammatory mediators,
      including transforming growth factor beta, which is a potent stimulus for
      collagen synthesis. Therefore, it may well be that CVI is a potential trigger
      factor for localized scleroderma. In addition, localized scleroderma may only
      develop if a certain amount of trigger factors are present - and resolves if one
      or more of the contributing factors (i.e. CVI) can be treated.

PMID- 16405620
TI  - Treatment of severe acne in Familial Mediterranean Fever.

PMID- 16405622
TI  - Thrombosed solitary angiokeratoma of Mibelli simulating malignant melanoma: the
      importance of dermoscopy in differential diagnosis.

PMID- 16405621
TI  - Patterned localized siderosis mimicking pigmented tumour.

PMID- 16405623
TI  - Efficacy of narrowband UVB phototherapy in early stage of mycosis fungoides.

PMID- 16405624
TI  - Behcet's disease with unusual cutaneous lesions.

PMID- 16405625
TI  - Systemic sclerosis-polymyositis overlap syndrome accompanied by autoimmune
      hepatitis and sarcoidosis of mediastinal lymphnodes.

PMID- 16405626
TI  - Multicentric reticulohistiocytosis - a case with minimal articular changes.

PMID- 16405627
TI  - The low seropositivity of hepatitis B virus in vitiligo patients.

PMID- 16405628
TI  - Generalized granuloma annulare in a patient with type II diabetes mellitus:
      successful treatment with isotretinoin.

PMID- 16405629
TI  - Squamous cell carcinoma of the skin complicating lupus vulgaris.

PMID- 16405630
TI  - Leiomyosarcoma of the vulva.

PMID- 16405631
TI  - Childhood lichen planus pemphigoides - a rare entity.

PMID- 16405632
TI  - Angioedema and urticaria due to isotretinoin therapy.

PMID- 16405633
TI  - Propylthiouracil-induced vasculitic oral ulcers with anti-neutrophil cytoplasmic
      antibody.

PMID- 16405635
TI  - Practitioner review: short-term and working memory impairments in
      neurodevelopmental disorders: diagnosis and remedial support.
AB  - BACKGROUND: This article provides an introduction to current models of working
      and short-term memory, their links with learning, and diagnosis of impairments.
      The memory impairments associated with a range of neurodevelopmental disorders
      (Down's syndrome, Williams syndrome, Specific Language Impairment, and
      attentional deficits) are discussed. METHODS: Methods of alleviating the adverse
      consequences of working and short-term memory impairments for learning are
      identified. CONCLUSION: Impairments of short-term and working memory are
      associated with learning difficulties that can be substantial, and that can be
      minimised by appropriate methods of remedial support.

PMID- 16405636
TI  - Abortion in young women and subsequent mental health.
AB  - BACKGROUND: The extent to which abortion has harmful consequences for mental
      health remains controversial. We aimed to examine the linkages between having an
      abortion and mental health outcomes over the interval from age 15-25 years.
      METHODS: Data were gathered as part of the Christchurch Health and Development
      Study, a 25-year longitudinal study of a birth cohort of New Zealand children.
      Information was obtained on: a) the history of pregnancy/abortion for female
      participants over the interval from 15-25 years; b) measures of DSM-IV mental
      disorders and suicidal behaviour over the intervals 15-18, 18-21 and 21-25 years;
      and c) childhood, family and related confounding factors. RESULTS: Forty-one
      percent of women had become pregnant on at least one occasion prior to age 25,
      with 14.6% having an abortion. Those having an abortion had elevated rates of
      subsequent mental health problems including depression, anxiety, suicidal
      behaviours and substance use disorders. This association persisted after
      adjustment for confounding factors. CONCLUSIONS: The findings suggest that
      abortion in young women may be associated with increased risks of mental health
      problems.

PMID- 16405637
TI  - Infant motor development is associated with adult cognitive categorisation in a
      longitudinal birth cohort study.
AB  - BACKGROUND: The relationship between the age of reaching infant developmental
      milestones and later intellectual function within the normal population remains
      unresolved. We hypothesised that the age of learning to stand in infancy would be
      associated with adult executive function and that the association would be
      apparent throughout the range of abilities, rather than confined to extremes.
      METHODS: The Northern Finland 1966 Birth Cohort is based upon 12,058 live-born
      children in a geographic and temporally defined population. Information on age at
      learning to stand without support was obtained at one year. At age 33-35 a random
      sample of 104 subjects underwent a neuropsychological test battery including
      tests of executive function (cognitive categorisation), visuo-spatial memory,
      verbal learning and visual object learning. We investigated associations between
      developmental data and adult neuropsychological test scores. RESULTS: There was a
      significant linear relationship between age of learning to stand and adult
      categorisation: the earlier the attainment of the milestone, the better was the
      categorisation. No such relationships were observed between infant
      neurodevelopment and adult cognition in other neuropsychological domains.
      CONCLUSION: Even within the normal range of development, early development in the
      gross motor domain is associated with better adult executive function (in tests
      of categorisation). Investigation of the determinants and sequelae of normal
      neural development will facilitate research into a variety of neurodevelopmental
      disorders.

PMID- 16405638
TI  - The relation between salivary cortisol, callous-unemotional traits, and conduct
      problems in an adolescent non-referred sample.
AB  - BACKGROUND: Previous research has suggested that adult psychopathic behavior and
      child callous-unemotional (CU) traits are uniquely related to low emotional
      reactivity. Salivary cortisol is a promising biological measure of emotional
      reactivity that has been relatively overlooked in research on CU traits and
      antisocial behavior. The current study examined for gender differences in the
      relation between resting salivary cortisol levels and CU traits in a non-referred
      adolescent sample. Salivary testosterone levels were assessed to provide
      discriminant validity for cortisol analyses and were not expected to bear a
      relation to CU traits. METHOD: An extreme groups strategy was used to recruit 108
      adolescents (53 male, 55 female) from a larger screening sample who exhibited
      various combinations of low and high scores on parent-report measures of CU
      traits and conduct problems. Resting saliva samples were assayed for cortisol and
      testosterone levels using a radioimmunoassay procedure. RESULTS: Consistent with
      prediction, male participants exhibiting elevated CU traits were uniquely
      characterized by low cortisol levels relative to male comparison groups (p<.05).
      Testosterone levels did not differentiate groups and no hormone effects were
      found for female participants. CONCLUSIONS: The current findings build upon
      recent research in suggesting that low cortisol may be a biological marker for
      male CU traits.

PMID- 16405639
TI  - Structural equation analysis of a hypothesised symptom model in the autism
      spectrum.
AB  - BACKGROUND: Several studies showed a different symptom structure underlying the
      spectrum of autistic-like disorders from the behaviour triad as mentioned in the
      DSM-IV. In the present study, a hypothesised symptom model for autism was
      constructed, based on earlier explorative findings, and was put to a confirmatory
      test. METHOD: Items from the Autism Diagnostic Interview-Revised (ADI-R) were
      used to examine the goodness of fit of the DSM-IV model, the hypothesised symptom
      model, and two additional models for autism. All models were tested in a group of
      255 verbal and nonverbal individuals with minor to severe autistic
      symptomatology. RESULTS: The DSM-IV model encountered estimation problems.
      Conversely, the hypothesised symptom model had no such problems and proved to
      have a better fit to the sample data than the two additional models for autism.
      However, some of the observed variables were weak indicators of the three latent
      factors in the model. CONCLUSIONS: The hypothesised symptom model appeared to be
      a plausible model in a group of individuals with a broad range of autistic
      behaviours and levels of functioning. Nevertheless, the stability of the model
      needs further examination in a larger group of individuals with disorders in the
      autism spectrum, and with varying degrees of intellectual functioning.

PMID- 16405640
TI  - Social behavior and peer relationships of victims, bully-victims, and bullies in
      kindergarten.
AB  - BACKGROUND: Although the prevalence of bully/victim problems in school-age
      children and adolescents has been investigated in many countries, only a few
      studies have been carried out among younger children. This study examines social
      behaviors and peer relationships of children involved in bully/victim problems in
      kindergarten. METHODS: Three hundred and forty-four five- to seven-year-old
      children participated. Children were categorized as victims, bully-victims,
      bullies, and non-involved by means of teacher ratings and peer nominations.
      Teachers completed questionnaires on children's social behavior patterns. Peer
      relationships were assessed by means of peer nominations and social cluster
      mapping. RESULTS: Compared to non-involved children, victims were more
      submissive, had fewer leadership skills, were more withdrawn, more isolated, less
      cooperative, less sociable, and frequently had no playmates. As expected, bullies
      and bully-victims were generally more aggressive than their peers. In addition,
      bully-victims were less cooperative, less sociable, and more frequently had no
      playmates than non-involved children. Bullies were less prosocial, and had more
      leadership skills than non-involved children. Bullies belonged to larger social
      clusters and were frequently affiliated with other bullies or bully-victims.
      CONCLUSIONS: We were able to establish distinct behavior patterns for bullies,
      bully-victims, and victims. Some of these social behaviors may be considered as
      risk factors for being victimized or becoming a bully. Our findings also
      emphasize the significance of peer relationships in bully/victim problems. On the
      one hand, victimized children's lack of friends might render them psychologically
      and socially vulnerable, and thus more prone to becoming easy targets. On the
      other hand, bullies seemed to be preferred playmates, particularly for other
      aggressive boys. This affiliation of aggressive children might lead to an
      increase in bullying behavior. Our understanding of the social and interactional
      nature of bullying and victimization has practical implications for prevention
      and intervention against bully/victim problems.

PMID- 16405641
TI  - Population and service characteristics of youth with schizophrenia-spectrum
      diagnoses in the Hawaii system of care.
AB  - BACKGROUND: Population and service characteristics were compared for youth (age 0
      18 years) with and without schizophrenia-spectrum disorders, who received public
      mental health services in Hawaii's comprehensive system of care between July 1,
      2000 and June 30, 2001. METHODS: Electronic records of youth with a diagnosis in
      the schizophrenia-spectrum (n=71) were compared to all other youth (n=13,904) who
      received services with respect to age, gender, ethnicity, comorbidity, type of
      service, and service cost. RESULTS: The schizophrenia-spectrum group had higher
      Asian representation, greater comorbidity, and was more likely to receive
      restrictive services for a higher average annual expense. When restrictive
      services were provided, they were of similar duration and intensity across
      groups. Almost all youth received less intensive services, but the schizophrenia
      spectrum group received a higher frequency or longer duration of such services.
      CONCLUSIONS: Although youth with schizophrenia-spectrum disorders were uncommon,
      collectively they represented a distinct population with above average service
      consumption. Future monitoring of interventions and outcomes may help develop
      systematic and effective treatment strategies for youth with schizophrenia
      spectrum disorders.

PMID- 16405642
TI  - Attention development in 10-month-old infants selected by the WILSTAAR screen for
      pre-language difficulties.
AB  - BACKGROUND: WILSTAAR comprises a programme for identifying and treating 8-10
      month-old infants who are at risk of language and cognitive difficulties. It has
      been adopted by health trusts, and included in Sure Start intervention schemes,
      throughout the UK. This study addresses one of the main queries raised by critics
      of the programme, by providing evidence about the psychological abilities of
      infants who fail the WILSTAAR screening assessment. METHODS: Thirty 10-month-old
      infants who failed the screen ('at-risk' infants) and 30 gender- and age-matched
      infants who passed the screen ('not-at-risk' infants) were assessed using a
      standard, validated measure of attention, the Distractibility Task. RESULTS: The
      at-risk infants were found to have poorer focused attention, and were more
      distractible, than the not-at-risk infants. The not-at-risk infants were quicker
      in deducing that distractor slides included in the task were of little
      importance, spent more sustained periods of time in focused attention on toy
      play, and were quicker in learning to use the information available in the task.
      CONCLUSIONS: The findings contribute to knowledge about infants' psychological
      development and provide partial support for the thinking underlying WILSTAAR.
      Evidence was found to support concerns about the accuracy of the WILSTAAR
      screening assessment, and issues about the trade-off between assessment age and
      the inclusion of WILSTAAR in routine services are discussed.

PMID- 16405643
TI  - Emotion regulation strategies in offspring of childhood-onset depressed mothers.
AB  - BACKGROUND: This study examines emotion regulation strategies used by children of
      mothers with childhood-onset depression (COD) and children of never-depressed
      mothers (NCOD). METHODS: Participants were 49 COD offspring (ages 4-7) and 37
      NCOD offspring (ages 4-7) and their mothers. Emotion regulation strategies were
      assessed observationally during a laboratory mood induction paradigm. RESULTS:
      COD offspring were more likely to focus on the delay object or task than NCOD
      offspring. Daughters of COD mothers were also more likely to wait passively and
      less likely to engage in active distraction than daughters of NCOD mothers. These
      findings were replicated using number of maternal depressive episodes.
      CONCLUSIONS: COD offspring, especially daughters, exhibit a more passive style of
      regulating emotion that may place them at risk for developing psychopathology.

PMID- 16405644
TI  - Maternal depression, child frontal asymmetry, and child affective behavior as
      factors in child behavior problems.
AB  - BACKGROUND: Despite findings that parent depression increases children's risk for
      internalizing and externalizing problems, little is known about other factors
      that combine with parent depression to contribute to behavior problems. METHODS:
      As part of a longitudinal, interdisciplinary study on childhood-onset depression
      (COD), we examined the association of mother history of COD, child frontal
      electroencephalogram asymmetry, and affective behavior with children's concurrent
      behavior problems. RESULTS: Children in the COD group had higher
      anxious/depressed and aggressive problems than did children in the control group,
      but this was qualified by a COD-by-asymmetry interaction effect. For COD but not
      control children, left frontal asymmetry was associated with both
      anxious/depressed and aggressive child problems. Children with left frontal
      asymmetry and low affect regulation behavior had higher anxious/depressed
      problems than did those with high affect regulation behavior. Boys with left
      frontal asymmetry had higher aggressive problems than did those with right
      frontal asymmetry. CONCLUSIONS: In children of mothers with COD, physiological
      and behavioral indices of affect regulation may constitute risks for behavior
      problems.

PMID- 16405645
TI  - Discrimination of temporal synchrony in intermodal events by children with autism
      and children with developmental disabilities without autism.
AB  - BACKGROUND: This project examined the intermodal perception of temporal synchrony
      in 16 young children (ages 4 to 6 years) with autism compared to a group of
      children without impairments matched on adaptive age, and a group of children
      with other developmental disabilities matched on chronological and adaptive age.
      METHOD: A preferential looking paradigm was used, where participants viewed non
      linguistic, simple linguistic or complex linguistic events on two screens
      displaying identical video tracks, but one offset from the other by 3 seconds,
      and with the single audio track matched to only one of the displays. RESULTS: As
      predicted, both comparison groups demonstrated significant non-random
      preferential looking to violations of temporal synchrony with linguistic and non
      linguistic stimuli. However, the group with autism showed an impaired, chance
      level of responding, except when presented with non-linguistic stimuli.
      CONCLUSIONS: Several explanations are offered for this apparently autism
      specific, language-specific pattern of responding to temporal synchrony, and
      potential developmental sequelae are discussed.

PMID- 16405646
TI  - Predictors of parent training efficacy for child externalizing behavior problems-
      a meta-analytic review.
AB  - BACKGROUND: The differential effectiveness of parent training has led researchers
      to examine a variety of child, parent, and familial variables that may predict
      treatment response. Studies have identified a diverse set of child, parent
      psychological/behavioral and demographic variables that are associated with
      treatment outcome and dropout. METHOD: The parent training literature was
      examined to isolate child, parent, and family variables that predict response to
      parent training for child externalizing behavior problems. A literature review
      was conducted spanning articles published from 1980 to 2004 of indicated
      prevention (children with symptoms) and treatment (children with diagnosis)
      studies. Meta-analyses were conducted to determine standardized effect sizes
      associated with the identified predictors. RESULTS: Many of the predictors of
      treatment response examined in this meta-analysis resulted in moderate
      standardized effect sizes when study results were subjected to meta-analytic
      procedures (i.e., low education/occupation, more severe child behavior problems
      pretreatment, maternal psychopathology). Only low family income resulted in a
      large standardized effect size. Predictors of drop-out resulted in standardized
      effect sizes in the small or insubstantial range. CONCLUSIONS: Response to parent
      training is often influenced by variables not directly involving the child, with
      socioeconomic status and maternal mental health being particularly salient
      factors.

PMID- 16405648
TI  - Report on apoptosis and immunity, 31 May-3 June 2005, Palm Cove, Queensland,
      Australia.
AB  - Apoptosis and Immunity 2005 was the ninth in a series of conferences centred on
      cellular immunity and particularly the molecular and cellular biology of
      cytotoxic lymphocytes, the first of which was held in Marseilles in 1981. More
      than 80 delegates from 20 countries attended the conference, which was held in
      the convivial surroundings of the Novotel Resort at Palm Cove, north Queensland.

PMID- 16405649
TI  - Activators of the energy sensing kinase AMPK inhibit random cell movement and
      chemotaxis in U937 cells.
AB  - AMP-activated protein kinase (AMPK) is a key energy sensor, known to regulate
      energy metabolism in diverse cell types. Hypoxia is encountered frequently in the
      microenvironments of inflammatory lesions and is a critical regulator of function
      in inflammatory cells. Energy deficiency is one of the consequences of hypoxia,
      but its potential role in modulating leucocyte function has received little
      attention. Using micropore chemotaxis assays to assess migratory responses of the
      monocyte-like cell line U937, it was found that the AMPK activators AICAR and
      phenformin rapidly reduced random migration (chemokinesis) as well as chemotaxis
      due to stromal cell-derived factor (SDF)1alpha. There was an approximate 50%
      reduction in both chemokinesis and chemotaxis following 30 min preincubation with
      both AICAR and phenformin (P < 0.01), and this continued with up to 24 h
      preincubation. The binding of SDF1alpha to its receptor CXCR4 was unaltered,
      suggesting AMPK was acting on downstream intracellular signalling pathways
      important in cell migration. As AMPK and statins are known to inhibit HMG CoA
      reductase, and both reduce cell migration, the effect of mevastatin on U937 cells
      was compared with AMPK activators. Mevastatin inhibited cell migration but
      required 24 h preincubation. As expected, the inhibitory effect of mevastatin was
      associated with altered subcellular localization of the Rho GTPases, RhoA and
      cdc42, indicating decreased prenylation of these molecules. Although the effect
      of AMPK activation was partially reversed by mevalonate, this was not associated
      with altered subcellular localization of Rho GTPases. The data suggest that
      activation of AMPK has a general effect on cell movement in U937 cells, and this
      is not due to inhibition of HMG CoA reductase. These are the first data to show
      an effect of AMPK on cell movement, and suggest a fundamental role for energy
      deficiency in regulating cellular behaviour.

PMID- 16405650
TI  - Apoptosis may underlie the pathology of zinc-deficient skin.
AB  - The trace element zinc is essential for the survival and function of all cells.
      Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The
      effects of zinc deficiency are particularly obvious in the skin, seen as an
      erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals
      degenerative changes within keratinocytes. Despite the well-documented
      association between zinc deficiency and skin pathology, it is not clear which
      cellular processes are most sensitive to zinc deficiency and could account for
      the typical pathological features. We used the cultured HaCaT keratinocyte line
      to obtain insight into the cellular effects of zinc deficiency, as these cells
      show many characteristics of normal skin keratinocytes. Zinc deficiency was
      induced by growing cells in the presence of the zinc chelator, TPEN, or by growth
      in zinc-deficient medium. Growth of cells in zinc-deficient medium resulted in a
      44% reduction of intracellular zinc levels and a 75% reduction in the activity of
      the zinc-dependent enzyme, 5'-nucleotidase, relative to the control cells. Over a
      period of 7 days of exposure to zinc-deficient conditions, no changes in cell
      viability and growth, or in the cytoskeletal and cell adhesion systems, were
      found in HaCaT cells. At 7 days, however, induction of apoptosis was indicated by
      the presence of DNA fragmentation and expression of active caspase-3 in cells.
      These results demonstrate that apoptosis is the earliest detectable cellular
      change induced by zinc deficiency in HaCaT keratinocytes. Our observations
      account for many of the features of zinc deficiency, including the presence of
      degenerate nuclei, chromatin aggregates and abnormal organization of keratin,
      that may represent the later stages of apoptosis. In summary, a major causal role
      for apoptosis in the pathology of zinc deficiency in the skin is proposed. This
      role is consistent with the previously unexplained diverse range of degenerative
      cellular changes seen at the ultrastructural level in zinc-deficient
      keratinocytes.

PMID- 16405651
TI  - Direct effects of IL-15 on corticosterone secretion by rat adrenocortical cells.
AB  - Cytokines might regulate the function of the hypothalamic-pituitary-adrenal axis.
      IL-15 is a potent non-T-cell-derived cytokine with IL-2-like activities. It has
      been shown that IL-15 can reverse the inhibition of glucocorticoids on PBMC. In
      vitro experiments were designed to assess the direct effect of IL-15 on
      corticosterone (CORT) secretion in the adrenal zona fasciculata-reticularis (ZFR)
      cells of male rats. Administration of IL-15 dose dependently decreased the basal
      and adrenocorticotropin-stimulated release of CORT and production of cAMP in ZFR
      cells. The stimulatory effect of forskolin (an adenylate cyclase activator) on
      CORT secretion and accumulation of cAMP in ZFR cells was attenuated by the
      administration of IL-15. However, 8-Br-cAMP (a cAMP analogue)-stimulated release
      of CORT was not affected by IL-15. Exogenous administration of IL-15 (10(-7)
      mol/L) significantly attenuated the pregnenolone (the substrate of 3beta
      hydroxysteroid dehydrogenase)- or deoxycorticosterone (the substrate of 11beta
      hydroxylase)-induced release of CORT. The results indicate that decrease of CORT
      secretion by IL-15 is in part because of (i) the decrease of adenylate cyclase
      activity and cAMP production and (ii) the inhibition of 3beta-hydroxysteroid
      dehydrogenase and 11beta-hydroxylase activities in rat ZFR cells.

PMID- 16405652
TI  - CTLA-4 lacking the cytoplasmic domain costimulates IL-2 production in T-cell
      hybridomas.
AB  - Optimal T-cell activation depends on the antigen-specific signal mediated by the
      TCR and engagement of costimulatory receptors such as CD28. CTLA-4, a homologous
      counterpart of CD28, is considered to be a crucial inhibitory receptor. To test
      its function separately from CD28 in an antigen-driven and ligand-specific model,
      we stably transfected the T-cell hybridomas A1.1 and DO11.10, which lack
      significant endogenous CD28 or CTLA-4 expression, with wild-type CTLA-4 (CTLA-4
      WT) and a construct lacking the cytoplasmic tail (tailless [TL]). Functional
      studies were carried out by co-incubation with APC expressing the B7 ligands for
      CTLA-4 and appropriate MHC molecules loaded with their cognate antigens. IL-2
      production on costimulation of CTLA-4WT and TCR did not differ significantly from
      untransfected controls. However, coligation of TCR and CTLA-4TL resulted in a
      vigorous IL-2 response specific for the interaction of CTLA-4 with B7. Thus, lack
      of the cytoplasmic tail converted CTLA-4 into a costimulatory receptor. This
      indicates that the CTLA-4 inhibitory function may not be attributable to
      sequestration of the common B7 ligands when competing with CD28. Rather, ligation
      of B7 by the CTLA-4 extracellular domain can enhance TCR activation, whereas in
      the full-length receptor, inhibitory signals mediated by the cytoplasmic domain
      may override this activation.

PMID- 16405654
TI  - Role of Bid-induced mitochondrial outer membrane permeabilization in granzyme B
      induced apoptosis.
AB  - Cytotoxic lymphocytes (CL) induce death of their targets by granule exocytosis.
      During this process, enzymes contained within cytotoxic granules (granzymes) are
      delivered to the target cell where the enzymes trigger the cell death by cleaving
      specific substrates. Granzyme B is the only granzyme that has been shown to
      induce cell death by apoptosis, but the exact pathway by which this is achieved
      has been the subject of hot debate. Furthermore, several other death-inducing
      granzymes have been identified; therefore, the exact contribution of granzyme B
      to CL-induced death is unclear. In this study, we discuss our recent findings on
      granzyme B-induced cell death and discuss the potential relevance of this pathway
      to CL-induced death of viral-infected and transformed cells.

PMID- 16405653
TI  - Addressing the mysteries of perforin function.
AB  - Perforin is a cytolytic protein stored in secretory granules of CTL and NK cells.
      It synergizes with proapoptotic serine proteases, granzymes, to deliver the
      lethal hit to virus-infected or transformed target cells. The mechanism of
      perforin action has not been described beyond its original characterization in
      the 1980s, and its role in human disease has remained elusive. This article
      addresses recent key advances in genetic, clinical and biochemical studies that
      have reignited the current interest in perforin biology.

PMID- 16405655
TI  - Serpins prevent granzyme-induced death in a species-specific manner.
AB  - Expression of serine protease inhibitors (serpins) is one of the mechanisms used
      by tumour cells to escape immune surveillance. Previously, we have shown that
      expression of serpins SPI-6 and SPI-CI, respectively, renders tumour cells
      resistant to granzyme B (GrB)-mediated death and granzyme M (GrM)-mediated death.
      To obtain better insight into the interaction between serpins and their target
      proteases, we investigated the roles of protease inhibitor (PI)-9 and SPI-6 in
      the resistance to GrB-mediated and CD95-mediated death in further detail. Neither
      human PI-9 nor its murine orthologue SPI-6 was capable of preventing CD95-induced
      apoptosis in murine or human cells, indicating that these serpins do not inhibit
      the activation of apical caspases in this pathway. High expression of PI-9 or SPI
      6 did prevent apoptosis induced by human GrB. Strikingly, only SPI-6, and not PI
      9, was capable of inhibiting murine GrB, suggesting that a difference in
      enzymatic specificity exists between the mouse and the human granzymes. In
      agreement with this suggestion, murine GrB was clearly less effective in inducing
      apoptosis in human cells. Similar species specificity was also observed for SPI
      CI and GrM when either their capacity to associate or the effectiveness of GrM
      induced cytotoxicity was analysed. Our findings therefore indicate a species
      diversity that has a clear effect on mixed in vitro effector target settings.

PMID- 16405656
TI  - TNF-related apoptosis-inducing ligand as a therapeutic agent in autoimmunity and
      cancer.
AB  - Recombinant, soluble TNF-related apoptosis-inducing ligand (TRAIL) is currently
      being developed as a promising natural immune molecule for trial in cancer
      patients because it selectively induces apoptosis in transformed or stressed
      cells but not in most normal cells. In cancer patients, phase 1 and 2 clinical
      trials using agonistic mAbs that engage the human TRAIL receptors DR4 and DR5
      have also provided encouraging results. It is now evident that TRAIL suppresses
      autoimmune disease in various experimental animal models, suggesting that the
      therapeutic value of recombinant TRAIL and agonistic DR4 and DR5 mAbs might also
      extend to the suppression of autoimmune disease. This review provides an insight
      into our current understanding of the role(s) of TRAIL in disease, with a
      specific focus on cancer and autoimmunity. We also emphasize biological agents
      and drugs that sensitize tumour cells to TRAIL-mediated apoptosis and discuss the
      potential molecular basis for their sensitization.

PMID- 16405657
TI  - Insights into the mechanisms of CMV-mediated interference with cellular
      apoptosis.
AB  - Apoptosis has the potential to function as a defence mechanism during viral
      infection. Identification of CMV mutants that cause the apoptotic death of
      infected cells confirmed that viral infection activates apoptotic pathways and
      that this process is counteracted by CMV to ensure efficient viral replication.
      The recent identification of CMV-encoded proteins that suppress cell death has
      greatly enhanced our understanding of the mechanisms used by this family of
      viruses to prevent apoptosis. CMV do not encode homologues of known death
      suppressing proteins, suggesting that the CMV family has evolved novel, more
      sophisticated strategies for the inhibition of apoptosis. The identification and
      characterization of the human CMV (HCMV)-encoded antiapoptotic proteins UL36
      (viral inhibitor of caspase-8 activation [vICA]) and UL37 (viral mitochondria
      localized inhibitor of apoptosis [vMIA]) have confirmed that CMV target unique
      apoptotic control points. For example, vMIA inhibits apoptosis by binding Bax and
      sequestering it at the mitochondrial membrane as an inactive oligomer. This
      knowledge not only provides a more complete understanding of the CMV replication
      process but also allows the identification of previously unrecognized apoptotic
      checkpoints. Because HCMV is an important cause of birth defects and an
      increasingly important opportunistic pathogen, a firm grasp of the mechanisms by
      which it affects cellular apoptosis may provide avenues for the design of
      improved therapeutic strategies. Here, we review the recent progress made in
      understanding the role of CMV-encoded proteins in the inhibition of apoptosis.

PMID- 16405658
TI  - Compartmentalization in T-cell signalling: membrane microdomains and polarity
      orchestrate signalling and morphology.
AB  - Lymphocyte function is regulated by complex signalling responses to diverse
      extracellular inputs, and a cell will often receive multiple, conflicting signals
      at one time. The mechanisms by which a lymphocyte integrates these signals into a
      single cellular response are not well understood. An important factor in the
      integration of signals likely involves the regulation of access of signalling
      molecules to cell surface receptors and of receptor signals to morphological
      determinants within the cell. Recent studies have led to important advances in
      our understanding of both the mechanisms by which signals are compartmentalized
      in T cells and the physiological role played by such compartmentalization. We
      review progress in the field, with a particular focus on membrane microdomains or
      lipid rafts and on cell polarity.

PMID- 16405661
TI  - Diagnostic difficulties in inflammatory bowel disease pathology.
AB  - This review summarizes some of the common diagnostic problems encountered by
      pathologists when evaluating patients with chronic colitis and in whom
      inflammatory bowel disease (IBD) is either suspected or within the differential
      diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show
      characteristic, but non-specific, pathological features that may overlap and
      result in a diagnosis of 'indeterminate colitis' (IC). However, other reasons why
      pathologists may entertain a diagnosis of IC include failure to recognize or
      accept certain 'hardcore' histological features as indicative of CD, an attempt
      to classify cases of chronic colitis based on mucosal biopsy material or in the
      absence of adequate clinical and radiographic information, and the presence of
      other disease processes that mask, or mimic, IBD. In addition, some cases of UC
      may show unusual CD-like features, such as discontinuous or patchy disease, ileal
      inflammation, extracolonic inflammation, granulomatous inflammation in response
      to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore,
      other forms of colitis, such as microscopic colitis, diverticulitis and diversion
      colitis may, on occasion, also show IBD-like changes. The clinical and
      pathological features that aid in the distinction between these entities, and
      others, are covered in detail in this review.

PMID- 16405662
TI  - Diagnosis and quantification of bone marrow fibrosis are significantly biased by
      the pre-staining processing of bone marrow biopsies.
AB  - AIMS: Marrow fibrosis (MF) is an unfavourable, often lethal complication of
      haematological neoplasms. Although biopsy technique and staining procedure are
      standardized, the prestaining processing of bone marrow biopsies (BMBs) varies
      markedly without any existing data on its significance for the diagnosis of MF.
      METHODS AND RESULTS: In this study on 712 BMBs from 296 patients with chronic
      idiopathic myelofibrosis (CIMF), chronic myeloid leukaemia (CML), or healthy bone
      marrow, MF was a characteristic complication of CML and CIMF. However, diagnosis
      and quantification of MF and detection of its prognostic significance were
      significantly biased by fixation, decalcification, embedding, marrow tissue
      shrinkage during biopsy processing and the thickness of marrow sections (P <
      0.000005). The relevance of these influences was explained by their effect on the
      marrow volume to which the fibre content was related, whereas the stainability of
      fibres was not affected. Semiquantitative grading of fibrosis and measurements of
      fibre density could not be adjusted to various methods of processing of bone
      marrow biopsies (P < 0.003). CONCLUSIONS: Evaluations of MF and its prognostic
      significance should consider the bias due to the prestaining processing of BMBs
      and the necessity of an adjustment to the thickness of tissue sections and the
      degree of marrow tissue shrinkage.

PMID- 16405663
TI  - HER-2/neu gene amplification in ovarian tumours: a comprehensive
      immunohistochemical and FISH analysis on tissue microarrays.
AB  - AIMS: Data on HER-2/neu overexpression, its correlation to prognosis and the
      success of treatment with Herceptin((R)) in ovarian carcinomas are scarce and
      contradictory. Therefore we assessed HER-2/neu expression and amplification in a
      large series of ovarian tumours by using tissue microarrays (TMAs). METHODS AND
      RESULTS: Two TMAs containing 173 invasive carcinomas, 36 borderline tumours, 20
      granulosa cell tumours, 14 carcinosarcomas, 11 benign cystadenoms and eight other
      pelvic tumours were constructed to assess HER-2/neu gene amplification by
      fluorescence in-situ hybridization (FISH) and immunohistochemistry.
      Immunohistochemistry was successful in 94.3%; 81.8% were HercepTest negative,
      11.3% were scored as 1+, 4.1% as 2+ and 2.8% as 3+, including 3.1% of invasive
      carcinomas, 2.8% of borderline tumours and 7.7% of carcinosarcomas; 83.6% could
      be analysed successfully by FISH revealing no aberration in 75.8%, low
      amplification in 2.7% and high amplification in 3.7% of the cases. In 17.8%
      monosomy, trisomy, polysomy or deletion could be detected. All cases with high
      level amplification had 2+ or 3+ scores on immunohistochemistry. CONCLUSIONS: TMA
      is a feasible tool to study a large number of ovarian cases. Correlation between
      immunohistochemistry and FISH was excellent. HER-2/neu overexpression or gene
      amplification does not correlate with histological tumour type, stage, grade or
      prognosis.

PMID- 16405664
TI  - Cytosolic overexpression of p62 sequestosome 1 in neoplastic prostate tissue.
AB  - AIMS: To investigate the expression of p62 in various prostatic tissues, and to
      demonstrate different immunohistochemical patterns of p62 expression in distinct
      pathological entities of the prostate. The p62 sequestosome 1 (SQSTM1) gene
      product is a multifunctional protein with ubiquitous expression in normal adult
      tissue. METHODS AND RESULTS: Overexpression of p62 was detected in prostate
      cancer cell lines and tissues by reverse transcriptase-polymerase chain reaction.
      Immunohistochemical staining for p62 was performed on 73 cases of paraffin
      embedded prostatic tissue. p62 was negative or weakly positive only in the
      nucleus (pattern N) of prostatic gland epithelium in nine normal and hyperplastic
      prostate specimens, whilst most cancerous tissue showed intense, uniform staining
      for p62 in the cytoplasm (pattern C). Of the prostate cancer specimens, 91%
      showed positive pattern C immunoreactivity. Of the cases with high-grade
      prostatic intraepithelial neoplasia (PIN) around cancer, 77% showed pattern C.
      However, in specimens from the patients without prostate cancer PIN displayed
      pattern C in only 32% of cases. Western blot analysis showed that all cancer cell
      lines expressed p62 in the cytoplasm but there was little nuclear expression.
      CONCLUSION: Cytosolic overexpression of p62 is a novel immunohistochemical
      characteristic in prostatic adenocarcinoma and high-grade PIN, suggesting that
      p62 might be a novel marker for prostatic malignancy.

PMID- 16405665
TI  - A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on
      21 cases.
AB  - AIMS: To report the clinicopathological findings of 21 cases of primary nodal
      marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma
      and few series have been published. METHODS AND RESULTS: The clinical data were
      characteristic of a disseminated disease at presentation: presence of peripheral
      and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and
      IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included
      peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and
      presence of serum M component (33%), while the previously reported association
      with hepatitis C virus and cryoglobulinaemia was not found. Relapses were
      frequent but the majority of patients receiving chemotherapy had a good initial
      response. Morphological features were heterogeneous and there were some
      differences compared with other marginal zone B-cell lymphomas (MZL). Pure
      monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B
      cell was observed more frequently (23%). Plasmacytoid or plasmacytic
      differentiation was a very common feature (61%). Large cells and a high mitotic
      count were also frequent (57%). CONCLUSION: NMZL can be distinguished from
      splenic MZL and extranodal MZL by its aggressive morphology and disseminated
      disease at presentation.

PMID- 16405666
TI  - Wound healing after paranasal sinus surgery: neutrophilic inflammation influences
      the outcome.
AB  - AIMS: After failure of medical treatment, functional endoscopic sinus surgery
      (FESS) remains the best treatment for chronic sinusitis (CS) and nasal polyposis
      (NP). The precise mechanisms involved in wound healing after sinus surgery remain
      unclear. The aim of this study was to explore systematically the different
      histomorphological processes and cell populations involved in the wound repair of
      the paranasal mucosa. METHODS AND RESULTS: Biopsy specimens from patients
      operated on for CS and NP were collected 1, 2 and 6 months after surgery and
      compared with baseline and control specimens. A pathologist blinded to biopsy
      status evaluated the haematoxylin/eosin-stained sections for oedema, fibrosis and
      inflammatory reaction, and the immunohistochemical preparations for epithelial
      replication, myofibroblasts, macrophages, neutrophils and eosinophils. Samples
      from NP showed significantly more oedema than those from CS. At baseline, oedema
      showed a significant correlation with macrophages, neutrophils and eosinophils,
      while fibrosis was inversely correlated with neutrophils. During healing, after a
      short increase at month 1, oedema decreased. Fibrosis and myofibroblasts showed
      an inverse relationship. Finally, during the postoperative period, both
      macrophages and neutrophils were increased when compared with controls.
      CONCLUSIONS: The severity of the neutrophilic inflammation appears to influence
      the formation of fibrosis during wound repair after sinus surgery.

PMID- 16405667
TI  - Persistent nodules at injection sites (aluminium granuloma) --
      clinicopathological study of 14 cases with a diverse range of histological
      reaction patterns.
AB  - AIMS: To assess and document the spectrum of histological appearances of
      persistent swellings which occur at injection sites following vaccination or
      allergen desensitization. METHODS AND RESULTS: Fourteen cases were studied. Four
      overlapping histological reaction patterns were evident. Ten cases showed at
      least focal fibrosis, fat necrosis and a mixed inflammatory cell infiltrate
      mainly in the subcutis, giving rise to the features of a non-specific septal and
      lobular panniculitis. The appearance of three cases, in addition to the non
      specific panniculitis pattern, also included prominent lymphoid follicles with
      germinal centres and a prominent perifollicular infiltrate resembling a lymphoma
      (pseudolymphoma pattern). A single case mimicked lupus profundus, with a
      perivascular and periadnexal infiltrate in the dermis and hyaline fat necrosis.
      Three cases showed a predominantly palisaded histiocytic infiltrate surrounding
      eosinophilic necrobiosis, in a pattern closely resembling deep granuloma annulare
      or rheumatoid nodule. The remaining case partly showed this appearance, but in
      combination with panniculitis, thus demonstrating an overlap of patterns. A
      common feature in all 14 cases was the focal presence of histiocytes with
      abundant violaceous granular cytoplasm. These were shown to contain aluminium on
      energy dispersive X-ray microanalysis. CONCLUSION: Persistent swellings at
      injections sites show a variety of overlapping patterns, which mimic other
      conditions. Identification of characteristic histiocytes with violaceous granular
      cytoplasm is the key distinctive feature allowing the correct diagnosis to be
      reached.

PMID- 16405668
TI  - Prevalence of hepatitis C virus infection in cases of B-cell lymphoma in Japan.
AB  - AIMS: To determine the prevalence of hepatitis C virus (HCV) infection in B-cell
      lymphoma in Japan. HCV infection and type II (monoclonal IgM) cryoglobulinaemia
      (CG) may be involved in the pathogenesis of low-grade B-cell lymphoma (ML) in
      southern Europe. METHODS AND RESULTS: Forty-five (11.3%) of 400 B-cell ML cases
      were HCV antibody (Ab) positive, which was significantly (P < 0.01) higher than
      the blood donors (2.5%). Among them, 28 diffuse large B-cell lymphoma (DLBCL)
      cases were included. In the primary sites, 10 (47.6%) of 21 splenic DLBCL and
      seven (23.3%) of 30 gastric DLBCL were HCV Ab positive, which were significantly
      (P < 0.05) higher than the myeloma cases (4.9%). HCV infection was rarely (4.2%)
      detected in 24 lymphoplasmacytic and salivary gland low-grade B-cell ML cases.
      Type II CG was detected in one myeloma case (3.5%) of 29 HCV+ B-cell ML. By real
      time polymerase chain reaction, HCV RNA was detected in fresh tumour tissues of
      all 11 B-cell ML cases examined. Lymphoma cells were positive for the envelope
      HCV non-structural (NS)3 and envelope (E2) proteins in six of eight examined B
      cell ML cases. CONCLUSIONS: The rare incidence of type II CG is characteristic of
      Japanese HCV+ ML patients and may influence the low incidence of low-grade B-cell
      ML. HCV infection may play a role in lymphomagenesis of splenic and gastric
      DLBCL.

PMID- 16405670
TI  - Urothelial neoplasia with plasmacytoid morphology.

PMID- 16405671
TI  - Desmin and myogenin reactivity in mesenchymal chondrosarcoma: a potential
      diagnostic pitfall.

PMID- 16405672
TI  - What is a significant lung asbestos fibre result?

PMID- 16405673
TI  - Metastases from bronchioloalveolar carcinomas associated with long-standing type
      1 congenital cystic adenomatoid malformations. A report of two cases.

PMID- 16405674
TI  - Cardiac myxoma with atypical glandular component, report of a case.

PMID- 16405675
TI  - Interstitial cells of Cajal (ICC) in mature cystic teratoma of the ovary.

PMID- 16405676
TI  - Lymphocytic lobulitis in breast core biopsy: a peritumoral phenomenon.

PMID- 16405677
TI  - Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms.

PMID- 16405679
TI  - Lack of agreement on predictors for metastasizing thin melanomas.

PMID- 16405678
TI  - Colonization of epithelial pilar neoplasms by melanocytes.

PMID- 16405680
TI  - Bacillus cereus is common in the environment but emetic toxin producing isolates
      are rare.
AB  - AIMS: To determine the incidence of emetic toxin producing Bacillus cereus in
      soil, animal faeces and selected vegetable produce to compare the results with
      the previously reported high incidence in rice paddy fields. To examine whether
      the emetic toxin has antibiotic activity. METHODS AND RESULTS: The incidence of
      emetic toxin producing B. cereus was evaluated by plating on selective agar 271
      samples of soils, animal faeces, raw and processed vegetables. Overall, 45.8% of
      samples were positive for B. cereus. One hundred and seventy-seven B. cereus
      isolates were recovered at 30 degrees C with the grand mean spore count being 2.6
      +/- 1.7 log(10) CFU g(-1) and 148 B. cereus isolates were recovered at 7 degrees
      C with the grand mean spore count being 2.2 +/- 1.2 log(10) CFU g(-1) of the 177
      B. cereus isolated at 30 degrees C, only 3 were positive for emetic toxin
      production at a titre of 1/64, 1/32, 1/16, respectively. Also, 1 of 148 B. cereus
      isolated at 7 degrees C was positive for emetic toxin production to a titre of
      1/128. All positive isolates came from washed or unwashed potato skins, one was
      psychrotrophic as determined by PCR and growth at 7 degrees C on subculture. The
      emetic toxin was not shown to have any antibiotic effects in growth inhibition
      studies. CONCLUSIONS: While B. cereus was a common isolate, the incidence of the
      emetic strain was rare. This is in contrast to previous findings of the high
      incidence in rice paddy fields and the processing environment, which may suggest
      rice is a selective area for growth of the emetic strain of B. cereus.
      SIGNIFICANCE AND IMPACT OF STUDY: The finding that a psychrotrophic isolate of B.
      cereus can produce emetic toxin is the first ever such observation and suggests
      the possibility that psychrotrophic isolates could grow in refrigerated fresh
      foods and cause emesis. The incidence of emetic B. cereus strains in rice paddy
      fields now requires further study for comparison with the low incidence found in
      other soils. The emetic toxin failed to inhibit the growth of other bacterial,
      fungal and yeast species. Whether the toxin (which is similar in structure to the
      antibiotic valinomycin) plays a competitive role in the environment therefore
      remains unclear.

PMID- 16405681
TI  - Assessing genetic diversity in plasmids from Escherichia coli and Salmonella
      enterica using a mixed-plasmid microarray.
AB  - AIMS: To compare genetic composition of plasmids using microarrays composed of
      randomly selected fragments of plasmid DNA. METHODS AND RESULTS: Separate shotgun
      libraries were constructed from plasmid DNA pooled from Escherichia coli and
      Salmonella enterica. Cloned fragments were used as probes for microarrays.
      Plasmid targets were labelled, hybridized overnight, and bound targets were
      imaged after enzymatic signal amplification. Control hybridizations demonstrated
      significantly higher signal when probes and targets shared >95% sequence
      identity. Diagnostic sensitivity and specificity of the assay was 95 and 99%,
      respectively. Cluster analysis showed close matches for replicate experiments
      with a high correlation between replicates (r = 0.91) compared with the
      correlation for nonreplicates (r = 0.09). Analysis of hybridization data from 43
      plasmids generated five distinct clusters, two for known serovar-specific
      plasmids, one for enterohemorrhagic E. coli plasmids, and two for plasmids
      harboring a recently disseminated antibiotic resistance gene (bla(CMY-2)).
      CONCLUSION: Mixed-plasmid microarrays are suitable for comparing genetic content
      of wild-type plasmids and hybridization results from this study suggest several
      novel hypotheses about plasmid gene exchange between E. coli and S. enterica.
      SIGNIFICANCE AND IMPACT OF STUDY: Mixed-plasmid microarrays permit rapid, low
      cost analysis and comparison of many plasmids. This ability is critical to
      understanding the source, fate, and transport of plasmids amongst commensal and
      pathogenic bacteria.

PMID- 16405682
TI  - Multiple characterizations of Listeria monocytogenes sensitive and insensitive
      variants to divergicin M35, a new pediocin-like bacteriocin.
AB  - AIMS: Divergicin M35 is a new class IIa bacteriocin produced by Carnobacterium
      divergicin M35. The bactericidal activity of this antimicrobial peptide was
      tested against a set of 11 strains of Listeria monocytogenes isolated from food.
      METHODS AND RESULTS: The minimal inhibitory concentration (MIC) was determined by
      the microdilution method. The strains tested displayed a different level of
      sensitivity to divergicin M35. L. monocytogenes LSD530, referred to as DivS
      strain, was the most sensitive and appeared to be inhibited by concentration of
      divergicin M35 below 0.13 microg ml(-1). The mutant resistant to divergicin M35,
      called DivM, was obtained from L. monocytogenes LSD530 (DivS) by gradually
      increasing the amounts of divergicin M35 until 1.3 microg ml(-1). Notably, DivM
      was stable after 50 generations. DivS parental strain was inhibited by a
      concentration of 4 microg ml(-1). L. monocytogenes LSD530 was shown to be
      resistant to divergicin M35 at 1.3 microg ml(-1). Remarkably, in the presence of
      divalent cations such as Ca(2+), Mg(2+) and Mn(2+), the lethality caused by
      divergicin M35 was reduced by 0.48, 0.54 and 0.63 log CFU per ml (after 18 h at
      30 degrees C), respectively. The total DNA profiles of DivS and DivM were
      similar. DivS and DivM showed variable sensitivity to antibiotics. The two
      dimensional (2-D) electrophoresis of cell wall proteins did not show any
      significant difference between DivS and DivM strains but their fatty acid
      composition showed a significant difference in C(16:0) content. CONCLUSIONS:
      Resistance to divergicin M35 is likely ascribed to modification in cell wall
      fatty acid composition rather than protein modification. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This study provides original results contributing to understanding
      of the resistance of L. monocytogenes to divergicin M35, a new class IIa
      bacteriocin.

PMID- 16405683
TI  - Safety properties and molecular strain typing of lactic acid bacteria from
      slightly fermented sausages.
AB  - AIM: To evaluate the biodiversity of lactobacilli from slightly fermented
      sausages (chorizo, fuet and salchichon) by molecular typing, while considering
      their safety aspects. METHODS AND RESULTS: Species-specific PCR, plasmid
      profiling and randomly amplified polymorphic DNA (RAPD)-PCR were used to
      characterize 250 lactic acid bacteria (LAB) isolated from 21 low acid Spanish
      fermented sausages. Lactobacillus sakei was the predominant species (74%)
      followed by Lactobacillus curvatus (21.2%) and Leuconostoc mesenteroides (4.8%).
      By plasmid profiling and RAPD-PCR 144 different strains could be differentiated,
      112 belonging to Lact. sakei, 23 to Lact. curvatus and 9 to Leuc. mesenteroides.
      Ion-pair high performance liquid chromatography was used to detect biogenic amine
      production. Tyramine and phenylethylamine were produced by 14.4 and 12.4% of the
      isolates, respectively, all belonging to the species Lact. curvatus. The
      production of tyramine was stronger than that of phenylethylamine. Partial
      sequencing of the tyrosine decarboxylase gene from Lact. curvatus was achieved. A
      specific PCR assay to detect the Lact. curvatus tyramine-producers was designed.
      The disc diffusion test was used to detect antibiotic resistance among the
      isolates. Most isolates displayed resistance to vancomycin and gentamicin. Only
      four strains were resistant to most of the antibiotics tested. None of the
      isolates were resistant to erythromycin. CONCLUSIONS: Lactobacillus sakei would
      be the species of choice for further use as starter culture in fermented sausage
      production. Strain typing and characterization of biogenic amine production
      together with antibiotic susceptibility testing for the selection of starter
      cultures could help to increase the quality and safety of the products.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Species-specific PCR, RAPD and plasmid
      profiling proved to be efficient at typing LAB at species and strain level.
      Information on biogenic amine production and transferable antibiotic resistance
      is important in order to avoid selection of strains with undesirable properties
      as starter cultures.

PMID- 16405684
TI  - Geographical variation in antibiotic resistance profiles of Escherichia coli
      isolated from swine, poultry, beef and dairy cattle farm water retention ponds in
      Florida.
AB  - AIMS: The aim of this study was to assess geographical variation in multiple
      antibiotic resistance (MAR) profiles of livestock Escherichia coli as well as to
      evaluate the ability of MAR profiles to differentiate sources of faecal
      pollution. METHODS AND RESULTS: More than 2000 E. coli isolates were collected
      from water retention ponds and manure of swine, poultry, beef and dairy farms in
      south, central and north Florida, and analysed for MAR using nine antibiotics.
      There were significant differences in antibiotic resistance of E. coli by season
      and livestock type for more than one antibiotic, but regional differences were
      significant only for ampicillin. Over the three regions, discriminant analysis
      using MAR profiles correctly classified 27% of swine, 49% of poultry, 56% of beef
      and 51% of dairy isolates. CONCLUSIONS: Regional variations in MAR combined with
      moderate discrimination success suggest that MAR profiles of E. coli may only be
      marginally successful in identifying sources of faecal pollution. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study demonstrates the existence of regional and
      seasonal differences in MAR profiles as well as the limited ability of MAR
      profiles to discriminate among livestock sources.

PMID- 16405685
TI  - Filtration, haze and foam characteristics of fermented wort mediated by yeast
      strain.
AB  - AIMS: To investigate the influence of the choice of yeast strain on the haze,
      shelf life, filterability and foam quality characteristics of fermented products.
      METHODS AND RESULTS: Twelve strains were used to ferment a chemically defined
      wort and hopped ale or stout wort. Fermented products were assessed for foam
      using the Rudin apparatus, and filterability and haze characteristics using the
      European Brewing Convention methods, to reveal differences in these parameters as
      a consequence of the choice of yeast strain and growth medium. CONCLUSIONS: Under
      the conditions used, the choice of strain of Saccharomyces cerevisiae effecting
      the primary fermentation has an impact on all of the parameters investigated,
      most notably when the fermentation medium is devoid of macromolecular material.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The filtration of fermented products has a
      large cost implication for many brewers and wine makers, and the haze of the
      resulting filtrate is a key quality criterion. Also of importance to the quality
      of beer and some wines is the foaming and head retention of these beverages. The
      foam characteristics, filterability and potential for haze formation in a
      fermented product have long been known to be dependant on the raw materials used,
      as well as other production parameters. The choice of Saccharomyces cerevisiae
      strain used to ferment has itself been shown here to influence these parameters.

PMID- 16405686
TI  - Morphological mutants of Gibberella fujikuroi for enhanced production of
      gibberellic acid.
AB  - AIMS: To examine the production of gibberellic acid by selected morphological
      mutants of Gibberella fujikuroi in liquid cultures. METHODS AND RESULTS: Mutants
      of G. fujikuroi having different morphological characteristics were selected
      after UV irradiation. The production of gibberellic acid by mutants that had
      different hyphal lengths was examined in shake flasks in media with different
      concentrations of nutrients as well as different volumes of the medium. Fed-batch
      fermenter study was performed to evaluate the mutant Mor-25 for growth and
      production of gibberellic acid. The broth was analysed by high performance liquid
      chromatography for fusaric acid, the common mycotoxin produced by strains of
      Fusarium. A variety of morphological mutants having different mycelial and
      soluble pigmentation as well as colony morphologies were generated from G.
      fujikuroi upon exposure to UV radiation. A nonpigmented mutant (Car-1) was
      selected as intermediate parent and later, mutants Mor-1 and Mor-25 were selected
      based on their distinct morphology. The colonies on regeneration agar plates were
      small, compact and dry. In liquid medium, mutant Mor-25 grew in a micro-pelleted
      form and the mycelium had short, highly branched hyphae, curly at tips with
      thick, swollen cells. Mutant Mor-25 grew rapidly in a low-cost medium containing
      defatted groundnut flour, sucrose and salts. In media with higher nutrient
      concentrations as well as larger volumes, it produced twofold more gibberellic
      acid than the parent. Fusaric acid, the common mycotoxin, was absent in the
      fermentation broth of mutant Mor-25. The mutants have been deposited in National
      Collection of Industrial Microorganisms (NCIM), National Chemical Laboratory,
      Pune, India under following culture collection numbers (Car-1, NCIM 1323; Mor-1,
      NCIM 1322; and Mor-25, NCIM 1321). CONCLUSIONS: Growth of unpigmented,
      morphological mutants of G. fujikuroi that led to lower viscosity in fermentation
      broth resulted in increased production of gibberellic acid. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The use of morphological mutants that have lower viscosity
      in liquid cultures for gibberellic acid production is not reported earlier.
      Similar mutants can be useful for other types of fungal fermentations also.

PMID- 16405687
TI  - Syntrophic-archaeal associations in a nutrient-impacted freshwater marsh.
AB  - AIMS: Evaluation of the composition, distribution and activities of syntrophic
      bacteria and methanogens in soils from eutrophic and low nutrient regions of a
      freshwater marsh, and to compare these results with those obtained from a similar
      study in the Florida Everglades. METHODS AND RESULTS: Culture dependent and
      independent approaches were employed to study consortia of syntrophs and
      methanogens in a freshwater marsh. Methanogenesis from butyrate oxidation was
      fourfold higher in microcosms containing soil from eutrophic regions of the marsh
      than from low nutrient regions. Propionate was oxidized in eutrophic microcosms
      at lower rates than butyrate and with lower yields of methane. Sequence analysis
      of 16S rRNA gene clone libraries from DNA extracted from microcosms and soils
      revealed differences such that the dominant restriction fragment length
      polymorphism (RFLP) phylotypes (representing 82-88% of clone libraries) from
      eutrophic soils clustered with fatty acid oxidizing Syntrophomonas spp. The four
      dominant RFLP phylotypes (representing 11-24%) from microcosms containing soils
      from low nutrient regions were sequenced, and clustered with micro-organisms
      having the potential for fermentative and syntrophic metabolism. Archaeal 16S
      rRNA sequence analysis showed that methanogens from eutrophic regions were from
      diverse families, including Methanomicrobiaceae, Methanosarcinaceae, and
      Methanocorpusculaceae, but clone libraries from low nutrient soils revealed only
      members of Methanosarcinaceae. CONCLUSIONS: These findings indicate that syntroph
      methanogen consortia differed with nutrient levels in a freshwater marsh.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is one of few studies addressing the
      distribution of fatty acid consuming-hydrogen producing bacteria (syntrophs) and
      their methanogenic partners in wetland soils, and the effects of eutrophication
      on the ecology these groups.

PMID- 16405688
TI  - First isolation of Shiga toxin 1d producing Escherichia coli variant strains in
      shellfish from coastal areas in France.
AB  - AIMS: This study was carried out to evaluate the presence of Shiga toxin
      producing Escherichia coli (STEC) and E. coli O157:H7 in shellfish from French
      coastal environments. METHODS AND RESULTS: Shellfish were collected in six
      growing areas or natural beds (B category) and nonfarming areas (D category) from
      July 2002 to August 2004. PCR detection of stx genes was performed on homogenized
      whole shellfish and digestive gland tissues enrichments. STEC strains were
      detected by colony DNA hybridization using a stx-specific gene probe and E. coli
      O157 strains were additionally searched by immunomagnetic separation with O157
      specific magnetic beads. Stx genes were detected in 40 of 144 (27.8%) sample
      enrichments from mussels, oysters or cockles, 32 of 130 enrichments (24.6%) were
      from B-category areas and eight of 14 (57.1%) from the D-category area. Five
      strains carrying stx(1) or stx(1d) genes and one stx negative, eae and ehxA
      positive E. coli O157:H7 were isolated from six of 40 stx-positive enrichments.
      No relation was found between the total E. coli counts in shellfish and the
      presence of STEC strains in the samples. CONCLUSIONS: The STEC strains of
      different serotypes and stx types are present in shellfish from French coastal
      environments. It is the first isolation of STEC stx1d strains in France.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Shellfish collected in coastal environments
      can serve as a vehicle for STEC transmission.

PMID- 16405689
TI  - Ectoines as compatible solutes and carbon and energy sources for the halophilic
      bacterium Chromohalobacter salexigens.
AB  - AIMS: To investigate the catabolism of ectoine and hydroxyectoine, which are the
      major compatible solutes synthesized by Chromohalobacter salexigens. METHODS AND
      RESULTS: Growth curves performed in M63 minimal medium with low (0.75 mol l(-1)
      NaCl), optimal (1.5 mol l(-1) NaCl) or high (2.5 mol l(-1) NaCl) salinity
      revealed that betaine and ectoines were used as substrate for growth at optimal
      and high salt. Ectoine transport was maximal at optimal salinity, and showed 3-
      and 1.5-fold lower values at low and high salinity respectively. The salt
      sensitive ectA mutant CHR62 showed an ectoine transport rate 6.8-fold higher than
      that of the wild type. Incubation of C. salexigens in a mixture of glucose and
      ectoine resulted in a biphasic growth pattern. However, CO(2) production due to
      ectoine catabolism was lower, but not completely abolished, in the presence of
      glucose. When used as the sole carbon source, glycine betaine effectively
      inhibited ectoine and hydroxyectoine synthesis at any salinity. CONCLUSIONS: The
      catabolic pathways for ectoine and hydroxyectoine in C. salexigens operate at
      optimal and high (although less efficiently) salinity. Endogenous ectoine(s) may
      repress its own transport. Ectoine utilization was only partially repressed by
      glucose. Betaine, when used as carbon source, suppresses synthesis of ectoines
      even under high osmolarity conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study is a previous step to the subsequent isolation and manipulation of the
      catabolic genes, so as to generate strains with enhanced production of ectoine
      and hydroxyectoine.

PMID- 16405690
TI  - Shiga toxin-producing Escherichia coli and enteropathogenic Escherichia coli in
      healthy goats in India: occurrence and virulence properties.
AB  - AIMS: To describe the occurrence and virulence gene pattern of shiga toxin
      producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) in healthy
      goats of Jammu and Kashmir, India. METHODS AND RESULTS: A total of 220 E. coli
      strains belonging to 60 different 'O' serogroups was isolated from 206 local
      (nonmigratory) and 69 migratory goats. All the 220 strains were screened for the
      presence of stx(1), stx(2), eaeA and hlyA genes. Twenty-eight E. coli (75.6%)
      strains from local and nine (24.3%) strains from migratory goats belonging to 18
      different serogroups showed at least presence of one virulence gene studied.
      Twenty-eight strains (16.47%) (belonging to 13 different serogroups) from local
      goats carried stx(1) gene alone or in combination with stx(2) gene, while as only
      one strain (2%) from migratory goats possessed stx(2) gene alone. Interestingly
      in the present study none of the STEC strains carried eaeA gene. Similarly, none
      of the strains from local goats possessed eaeA and none of the migratory goats
      possessed stx(1) gene. Eight strains (16%) (belonging to four different
      serogroups) from migratory goats carried eaeA gene. Twenty-five (14.7%) and seven
      (14%) strains from local and migratory goats harboured hlyA gene respectively.
      CONCLUSIONS: Healthy goats of Jammu and Kashmir state serve as a reservoir of
      STEC and EPEC. Further studies in this direction are needed to work out whether
      or not they are transmitted to humans in this part of world. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study is the first report of isolation of STEC and EPEC
      strains from healthy goats in Jammu and Kashmir State of India, which could be a
      source of infection to humans.

PMID- 16405691
TI  - The dynamics of major fibrolytic microbes and enzyme activity in the rumen in
      response to short- and long-term feeding of Sapindus rarak saponins.
AB  - AIMS: To investigate the short- and long-term effects of an extract of Sapindus
      rarak saponins (SE) on the rumen fibrolytic enzyme activity and the major
      fibrolytic micro-organisms. METHODS AND RESULTS: Two feeding trials were
      conducted. In the short-term trial, four fistulated goats were fed a basal diet
      containing sugar cane tops and wheat pollard (65:35, w/w) and were supplemented
      for 7 days with SE at a level of 0.6 g kg(-1) body weight. Rumen liquor was taken
      before, during and after SE feeding. In the long-term trial, 28 sheep were fed
      the same basal diet as the goats and were supplemented for 105 days with 0.24,
      0.48 and 0.72 g kg(-1) body mass of the extract. Rumen liquor was taken on days
      98 and 100. Protozoal numbers were counted under the microscope. Cell wall
      degradation was determined by enzyme assays and the major fibrolytic micro
      organisms were quantified by dot blot hybridization. Sapindus extract
      significantly depressed rumen xylanase activity in both trials and
      carboxymethylcellulase activity in the long-term trial (P < 0.01). Fibrobacter
      sp. were not affected by the SE in both trials, while ruminococci and the
      anaerobic fungi showed a short-term response to the application of saponins.
      Protozoal counts were decreased only in the long-term trial with sheep.
      CONCLUSION: These data suggest that there is an adaptation of Ruminococcus albus,
      Ruminococcus flavefaciens and Chytridiomycetes (fungi) to saponin when fed over a
      long period. The fact that no correlation between the cell wall degrading enzyme
      activities and the cell wall degrading micro-organisms was observed suggests that
      the organisms tracked in this experiment are not the only key players in ruminal
      cell wall degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: Sapindus rarak
      saponins partially defaunate the rumen flora. Their negative effect on cell wall
      degradation, however, is not related to rumen organisms currently recognized as
      the major cell wall degrading species. The adaptation of microbes in the long
      term feeding experiment suggests that the results from short-term trial on the
      ruminal microbial community have to be interpreted carefully.

PMID- 16405692
TI  - Partial characterization of enterocin MR99 from a corn silage isolate of
      Enterococcus faecalis.
AB  - AIMS: To assess the inhibitory activity on Gram-positive and Gram-negative
      bacteria of several species of enterococci recovered from a natural corn silage.
      METHODS AND RESULTS: The inhibitory activity of strains of Enterococcus faecalis
      (58), Enterococcus faecium (35), Enterococcus gallinarum (3) and Enterococcus
      casseliflavus (4) were studied employing indicator strains from various sources
      (clinical, food and ATCC). Enterococcus faecalis MR99, the only strain with
      inhibitory activity, inhibited other enterococci, Listeria spp., Staphylococcus
      aureus, Clostridium spp., Bacillus spp., Escherichia coli, Shigella sonnei and
      Shigella flexneri. The bacterium contained only one conjugative pheromone
      responsive plasmid. The partially chromatography-purified MR99 enterocin (PPE)
      had a molecular weight of approx. 5000 Da and a pI of 6.2, was sensitive to
      proteolytic enzymes and could be extracted in benzene and butanol. It appeared
      stable to adjustment of pH 4.0, 5.0, 6.0, 7.0 and 8.0 and was resistant to heat.
      Inactivation was at 15 min at 121 degrees C. Enterocin MR99 was bactericidal on
      strains of Listeria monocytogenes, Staph. aureus, and bovine mastitis agents, it
      was bacteriostatic on E. coli. Although enterocins MR99 and AS48 have inhibitory
      activity on Gram-negative bacilli, PCR studies demonstrated a lack of
      relationship between them. CONCLUSIONS: The active component had a protein
      nature, was resistant to heat and presented a wide inhibitory spectrum.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The biological properties of Ent. faecalis
      MR99 suggest that this strain merits further investigations so it can be applied
      in human and veterinary health programmes.

PMID- 16405694
TI  - Use of IgG avidity ELISA to differentiate acute from persistent infection with
      Salmonella Dublin in cattle.
AB  - AIMS: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to
      differentiate between acute and persistent infection with Salmonella (S.) Dublin
      in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in
      acute and persistent infections differ. METHODS AND RESULTS: Animals were
      selected from two herds with long-term infection (years) and two herds recently
      infected (<3 months). Forty-seven animals were categorized into groups based on
      the persistence of their antibody level in milk. Based on titre from two serial
      dilutions the avidity index (AI) was calculated for IgG (IgG-AI), IgG(1) (IgG(1)
      AI) and IgG(2) (IgG(2)-AI). The mean IgG-AI for suspected carrier animals with
      either persistently high (group 1) or persistently high to medium high (group 2)
      antibody levels was significantly (P = 0.003) higher (32.1% and 38.4%) than for
      acutely infected animals (21.7% and 22.3%). The probability of being a suspect
      carrier was associated with IgG-AI, antibody level in the sample and age.
      However, the effect of age could be the result of a biased sample selection.
      Specificities and sensitivities were calculated at a range of cut-off values for
      IgG-AI and IgG(1)-AI. Overall, IgG(2)-AI was high compared with IgG(1)-AI, and
      there was no difference in IgG(2)-AI between infection groups. There was no
      difference in the ratio IgG(2):IgG(1) for acute and persistent infection groups.
      CONCLUSIONS: Assuming that a persistently high antibody response is indicative of
      persistent infection with S. Dublin in cattle, it can be concluded that the IgG
      AI can aid in differentiating between acute and long-term infection on herd
      level. However, for the test to be useful as an alternative tool to repeated
      sampling over time for detection of persistently infected carriers during control
      strategies in cattle herds, the test needs to be optimized and studied further in
      a larger sample of well-characterized infections in cattle. The affinity of
      IgG(2) is higher than IgG(1) early in the S. Dublin infection. There appears to
      be no difference in the IgG(2)-AI between the acute and chronic infection stages.
      SIGNIFICANCE AND IMPACT OF THE STUDY: For decades the strategies for detection of
      persistently infected cattle in S. Dublin infected herds have involved repeated
      bacteriological culture of faecal samples or repeated antibody measurements over
      several months. Both methods are time consuming and costly, leaving a new method
      for detection of carrier animals based on a single sampling highly desirable.
      This study illustrates a tool, IgG-AI, which may prove useful, although more
      validation of the method is required before it is used in practice.

PMID- 16405693
TI  - Evaluation of live-culture-producing lacticin 3147 as a treatment for the control
      of Listeria monocytogenes on the surface of smear-ripened cheese.
AB  - AIMS: A live Lactococcus lactis culture, producing the two-component broad
      spectrum bacteriocin lacticin 3147, was assessed for ability to inhibit the food
      pathogen Listeria monocytogenes on the surface of smear-ripened cheese. METHODS
      AND RESULTS: In initial experiments, the addition of Listeria to a lacticin 3147
      containing fermentate produced with L. lactis DPC4275 (a transconjugant strain
      derived from L. lactis DPC3147) resulted in at least a 4 log reduction of the
      pathogen in 30 min. Two separate trials were performed in order to assess the
      most suitable method for application of the potential protective culture to smear
      ripened cheese. In the initial trial, the L. lactis was sprayed onto the surface
      of the cheese either before or after Listeria was deliberately applied.
      Application of the culture following Listeria challenge, yielded up to a 1000
      fold reduction of the pathogen in contrast to the pretreatment where Listeria
      numbers were unaffected. In a further trial, three applications of the live
      lacticin 3147-producing culture was used on a cheese surface containing Listeria.
      Listeria numbers were found to be up to 100-fold lower than in the cheese treated
      with L. lactis DPC4268 (control). CONCLUSION: While application of the live
      lacticin 3147 producer did not give complete elimination of the pathogen the
      results nonetheless demonstrate the potential of the bioprotectant for improving
      the safety of smear-ripened cheeses and particularly those that contain low level
      contamination with Listeria. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      application of lacticin 3147 as a live-culture can serve as a bioprotectant for
      the control of L. monocytogenes on the surface of smear-ripened cheese.

PMID- 16405696
TI  - Development and evaluation of triplex PCR for direct detection of mycobacteria in
      respiratory specimens.
AB  - AIMS: To develop a method for the simultaneous detection of Mycobacterium
      tuberculosis, Mycobacterium avium-intracellularecomplex (MAC), and other
      mycobacteria in clinical specimens using triplex PCR. METHODS AND RESULTS: The
      target of amplification was the internal transcribed spacer region between the
      l6S and 23S rDNA genes. Twenty-two mycobacterial type strains, 118 M.
      tuberculosis, 87 other mycobacteria, 75 nonmycobacterial pathogens, 115
      respiratory specimens from confirmed cases of tuberculous or other mycobacterial
      diseases, and sputa from 50 patients with nonmycobacterial respiratory diseases
      were tested. In M. tuberculosis, 322 bp pan-mycobacterial and 133 bp species
      specific bands were observed. In MAC, the respective bands were 322 and 84 bp.
      The other mycobacteria showed single pan-mycobacterial bands of approx. 300-350
      bp. Nonspecific amplicons were not found in any of the nonmycobacterial
      pathogens. In the tuberculosis specimens, 96.4% of smear-positive specimens and
      70.2% of smear-negative specimens showed positive reactions. Specimens from two
      patients with MAC infection were MAC positive. Only 1 of 50 specimens from
      nonmycobacterial diseases was positive (2.0%). CONCLUSION, SIGNIFICANCE AND
      IMPACT OF THE STUDY: Triplex PCR enables accurate and rapid diagnosis of
      tuberculosis and probably is useful for the detection of MAC and other
      mycobacteria in respiratory specimens.

PMID- 16405695
TI  - Comparison of Campylobacter isolated from humans and food-producing animals in
      Japan.
AB  - AIMS: To compare the antimicrobial resistance, serotypes and flagellin gene types
      of Campylobacter isolated from humans and food-producing animals and thereby
      facilitate elucidation of the origin of Campylobacter causing human infection in
      Japan. METHODS AND RESULTS: The MIC values of ampicillin, dihydrostreptomycin,
      gentamicin, erythromycin, oxytetracycline, nalidixic acid and enrofloxacin for
      Campylobacter isolated from humans (134 isolates), cattle (38 isolates), pigs (69
      isolates), layers (84 isolates) and broilers (51 isolates) were compared. The
      MIC(90) values of ampicillin for Campylobacter jejuni isolates from poultry were
      higher than those from humans and cattle. Campylobacter coli that was resistant
      to dihydrostreptomycin and erythromycin was observed at a higher frequency in
      humans and pigs than in poultry. The restriction fragment profiles of flaA of
      human, bovine and broiler isolates were analysed by clustering, and the isolates
      were classified into five clusters. Cluster I contained only human and bovine
      isolates. Clusters III, IV and V contained human, bovine and broiler isolates.
      CONCLUSIONS: Campylobacter isolates from humans included isolates that exhibited
      characteristics identical to those of the bovine, porcine and poultry isolates.
      SIGNIFICANCE AND IMPACT OF THE STUDY: In addition to poultry, cattle and pigs are
      believed to be sources of campylobacteriosis in Japan.

PMID- 16405697
TI  - Factors affecting the activity of bovicin HC5, a bacteriocin from Streptococcus
      bovis HC5: release, stability and binding to target bacteria.
AB  - AIMS: To determine the factors affecting the release, stability and binding of
      bovicin HC5 to sensitive bacteria. METHODS AND RESULTS: Stationary phase
      Streptococcus bovis HC5 cultures had little cell-free bovicin HC5 activity until
      the final pH was <5.0, and even more bacteriocin was released by treatment with
      acidic NaCl (pH 2.0, 100 mmol l(-1)). Cultures grown with Tween 80 had more cell
      free bovicin HC5 than untreated controls, but this nonionic detergent enhanced
      activity rather than release. Bovicin HC5 binding to S. bovis JB1 (a susceptible
      strain) was greater at pH values <6.0. Bovicin HC5 bound other sensitive Gram
      positive bacteria, but not Gram-negative species. Cultures retained most of their
      activity for 35 days, but only if the final pH was <5.6. If the final pH was
      >5.6, peptidases destroyed much of the activity. CONCLUSIONS: Bovicin HC5 remains
      cell associated until the culture pH is <5.0, but it can be easily dissociated
      from the cell surface by acidic NaCl. It is highly stable in acidic environments
      and only binds sensitive bacteria at pH values <6.0. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Streptococcus bovis HC5 does not have generally regarded as safe
      status. However, bovicin HC5 has a broad spectrum of activity and sensitive
      bacteria do not become resistant. Based on these results, bovicin HC5 may be a
      useful bacteriocin model.

PMID- 16405698
TI  - Genotyping of Campylobacter spp. from retail meats by pulsed-field gel
      electrophoresis and ribotyping.
AB  - AIMS: To determine the genetic relatedness of Campylobacter spp. from retail meat
      products, and compare the discriminatory power of pulsed-field gel
      electrophoresis (PFGE) and automatic ribotyping. METHODS AND RESULTS: A total of
      378 Campylobacter isolates recovered from 159 raw meats (130 chicken, 25 turkey,
      three pork and one beef) sampled from 50 retail grocery stores of four
      supermarket chains in the Maryland suburban area from August 1999 to July 2000
      were analysed by PFGE with SmaI, 120 isolates of which were also characterized by
      ribotyping with PstI using RiboPrinter system. A total of 148 unique PFGE
      patterns were identified, 91 of which were present in multiple Campylobacter
      isolates and 24 in multiple meat samples. Nineteen Campylobacter clones with
      identical PFGE patterns recurred frequently (up to nine times) throughout the
      sampling period. Comparing ribotyping with PFGE, we identified 44 PFGE patterns
      and 22 RiboGroups among the 120 isolates tested. Multiple PFGE patterns within
      one RiboGroup were commonly observed, as well as multiple RiboGroups within one
      PFGE pattern. CONCLUSIONS: Although Campylobacter present in retail meats were
      genetically diverse, certain clones persisted in poultry meats. PFGE had a
      greater discriminatory power than ribotyping, and the two methods were
      complementary in genotyping Campylobacter. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Genomic DNA fingerprinting of Campylobacter confirmed diverse and recurrent
      Campylobacter clones in the retail meats, which provides additional data for a
      better understanding of the epidemiological aspect of Campylobacter infection.

PMID- 16405699
TI  - Growth-inhibiting effects of concentrations of fusaric acid on the growth of
      Bacillus mojavensis and other biocontrol Bacillus species.
AB  - AIMS: To determine the effects of concentrations of fusaric acid on the growth of
      several strains of the biocontrol bacterial endophyte Bacillus mojavensis and
      other species within the Bacillus subtilis group, as well as the genetic
      relationships within this small group of Gram-positive bacteria, and their
      antagonisms to Fusarium verticillioides, which produce fusaric acid. METHODS AND
      RESULTS: The growth of 50 Bacillus strains and species were tested at two
      concentrations of fusaric acid determined in maize infected by an isolate of F.
      verticillioides. Molecular characterizations of the strains and species of
      bacteria were determined with an automated ribotyper. The growth of bacteria
      measured under both concentrations with an automated turbidometer, Bioscreen,
      indicated that fusaric acid was toxic to most strains of the bacterial endophyte
      B. mojavensis. However, the effects of these two concentrations on other Bacillus
      species varied in that fusaric acid was either bacteriocidal or bacteriostatic to
      most species. CONCLUSIONS: These data indicate that the concentrations of fusaric
      acid are inhibitory to the growth of most Bacillus species, some of which are
      used as biocontrol agents. This suggests that the endophytic and saprophytic
      states of F. verticillioides and other Fusarium species cannot be controlled by
      fusaric-acid-sensitive Bacillus species. SIGNIFICANCE AND IMPACT OF STUDY:
      Mycotoxic Fusarium species, such as F. verticillioides, are competitive because
      all produce fusaric acid, which is inhibitory to biocontrol bacteria, and mutants
      tolerant to fusaric acid must be developed in order to be effective on biocontrol
      bacteria.

PMID- 16405700
TI  - Antifungal and new metabolites of Myrothecium sp. Z16, a fungus associated with
      white croaker Argyrosomus argentatus.
AB  - AIMS: Fungal infection is still a life-threatening risk for the immunocompromised
      population such as AIDS patients and those who receive treatments with
      immunosuppressors and/or frequent administrations of wide-spectrum antibiotics,
      which inevitably lead to the drug resistance and unbalanced microflora
      populations. The present work was accordingly performed to characterize more
      potent antifungal metabolites from various cultures of marine fungi residing in
      white croaker Argyrosomus argentatus. METHODS AND RESULTS: The three most common
      opportunistic human pathogens Candida albicans (CCCCM ID 00148), Aspergillus
      niger (CCCCM ACCC 30005) and Trichophyton rubrum (CCCCM ID 00001) were selected
      as test fungi. A total of 16 cultivable fungal strains were isolated from the
      variant tissues of Ar. argentatus collected from the Yellow Sea, followed by
      preliminary antifungal screenings of the EtOAc extracts of the corresponding
      cultures. As a result, the inhibition of the three target fungi, plus being
      allergic to isolators' skin, were discerned with the EtOAc extract of the fungus
      under the isolation number Z16 that was identified subsequently as Myrothecium
      sp. by a combination of morphological and 18S rDNA finger-typing characteristics.
      A follow-up bioassay fractionation of the EtOAc extract, in conjunction with
      spectral analyses [MS, (1)H-NMR, (13)C-NMR, distortionless enhancement by
      polarization transfer (DEPT), heteronuclear multiple quantum coherence (HMQC) and
      heteronuclear multiple bond resonance (HMBC)] wherever required, afforded
      eventually the characterization of a new acid (compound 1: 4,5-ditridecyl
      octanedioic acid), three macrocyclic trichothecenes including roridin A (compound
      2), verrucarin A (compound 3) and 8beta-acetoxy-roridin H (compound 4), (22E,24R)
      cerevisterol (compound 5) and N-phenyl-beta-amino-naphthalene (compound 6). In
      vitro antifungal tests showed that the three trichothecenes were active against
      A. niger, T. rubrum and C. albicans with MICs of 31.25, 62.5 and 125 microg ml(
      1) for compound 2, 250, 125 and 31.25 microg ml(-1) for compound 3 as well as
      125, 62.5 and 125 microg ml(-1) for compound 4 respectively. The MICs of
      ketoconazole (co-assayed herewith as a positive reference) against A. niger, T.
      rubrum and C. albicans were 31.25, 250, 31.25 microg ml(-1) respectively. A
      preliminary structure-activity relationship of the antifungal trichothecenes was
      highlighted in brief. CONCLUSIONS: The present investigation demonstrated that
      marine fungus Myrothecium sp. Z16 associated with white croaker (Ar. argentatus),
      was an efficient producer of a new acid and antifungal trichothecenes, the latter
      presumably being also the allergic substances in the culture. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The title marine fungus was investigated to be a resource of
      new aliphatic acid, and trichothecenes with potent antifungal and dermal toxic
      actions.

PMID- 16405701
TI  - A novel index for analysing the response of a microbial culture to changes in the
      environmental variables during cultivation.
AB  - AIMS: To analyse the sensitivity of a microbial culture to variations in the
      cultivation conditions by using the motile intensity of the cells. METHODS AND
      RESULTS: Batch cultures of Bacillus thuringiensis were used to study the
      sensitivity of the cells to pulse changes in pH, temperature and oxygen supply. A
      droplet of the culture sample was visualized under an optical microscope and the
      image of the moving cells was captured with a computer controlled display camera
      attached to the microscope. Motile intensity was computed directly using an image
      analysis programme. The results showed that the different phases of cell growth
      exhibited different motile intensities. The motile intensity changed remarkably
      at the high level of the motile intensity, when the environmental variables are
      changed. CONCLUSIONS: The product formation was considerably reduced when a
      disturbance was applied at the high magnitude of motile intensity. SIGNIFICANCE
      AND IMPACT OF STUDY: Monitoring the motile intensity by image analysis is simple
      and makes it an attractive method for assessing the effect of environmental
      variables on the growth and product formation of microbial cultures.

PMID- 16405702
TI  - Genetic characterization and antibiotic resistance of Campylobacter spp. isolated
      from poultry and humans in Senegal.
AB  - AIMS: The main objectives of this study were to investigate the diversity of
      Campylobacter genotypes circulating in Senegal and to determine the frequency of
      antibiotic resistance. METHODS AND RESULTS: Strains of Campylobacter jejuni
      isolated from poultry (n = 99) and from patients (n = 10) and Campylobacter coli
      isolated from poultry (n = 72) were subtyped by pulsed-field gel electrophoresis
      (PFGE). The pulsotypes obtained after digestion by SmaI and KpnI revealed a
      significant genetic diversity in both species, but without any predominant
      pulsotypes. However, farm-specific clones were identified in the majority of
      poultry houses (76.5%). Human and poultry isolates of C. jejuni had common PFGE
      patterns. High quinolone-resistance rates were observed for C. jejuni (43.4%) and
      C. coli (48.6%) isolates obtained from poultry. CONCLUSIONS: The results showed a
      genetic diversity of Campylobacter between farms indicating multiple sources of
      infection; but specific clones had the ability to colonize the broiler farms. The
      antimicrobial resistance patterns were not related to any specific PFGE pattern
      suggesting that resistance was due to the selective pressure of antibiotic usage.
      Campylobacter with similar genotypes were circulating in both human and poultry.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study is important for the
      understanding of the epidemiology of Campylobacter in broiler farms in Senegal.
      It also emphasizes the need for a more stringent policy in the use of
      antimicrobial agents in food animals.

PMID- 16405703
TI  - Re-forming relationships in health care. Papers from the ninth biennual
      Regenstrief Conference.

PMID- 16405704
TI  - The role of the student-teacher relationship in the formation of physicians. The
      hidden curriculum as process.
AB  - Relationship-Centered Care acknowledges the central importance of relationships
      in medical care. In a similar fashion, relationships hold a central position in
      medical education, and are critical for achieving favorable learning outcomes.
      However, there is little empirical work in the medical literature that explores
      the development and meaning of relationships in medical education. In this essay,
      we explore the growing body of work on the culture of medical school, often
      termed the "hidden curriculum." We suggest that relationships are a critical
      mediating factor in the hidden curriculum. We explore evidence from the
      educational literature with respect to the student-teacher relationship, and the
      relevance that these studies hold for medical education. We conclude with
      suggestions for future research on student-teacher relationships in medical
      education settings.

PMID- 16405705
TI  - Delving below the surface. Understanding how race and ethnicity influence
      relationships in health care.
AB  - There is increasing evidence that racial and ethnic minority patients receive
      lower quality interpersonal care than white patients. Therapeutic relationships
      constitute the interpersonal milieu in which patients are diagnosed, given
      treatment recommendations, and referred for tests, procedures, or care by
      consultants in the health care system. This paper provides a review and
      perspective on the literature that explores the role of relationships and social
      interactions across racial and ethnic differences in health care. First, we
      examine the social and historical context for examining differences in
      interpersonal treatment in health care along racial and ethnic lines. Second, we
      discuss selected studies that examine how race and ethnicity influence clinician
      patient relationships. While less is known about how race and ethnicity influence
      clinician-community, clinician-clinician, and clinician-self relationships, we
      briefly examine the potential roles of these relationships in overcoming
      disparities in health care. Finally, we suggest directions for future research on
      racial and ethnic health care disparities that uses a relationship-centered
      paradigm.

PMID- 16405706
TI  - The expression of emotion through nonverbal behavior in medical visits.
      Mechanisms and outcomes.
AB  - Relationship-centered care reflects both knowing and feeling: the knowledge that
      physician and patient bring from their respective domains of expertise, and the
      physician's and patient's experience, expression, and perception of emotions
      during the medical encounter. These processes are conveyed and reciprocated in
      the care process through verbal and nonverbal communication. We suggest that the
      emotional context of care is especially related to nonverbal communication and
      that emotion-related communication skills, including sending and receiving
      nonverbal messages and emotional self-awareness, are critical elements of high
      quality care. Although nonverbal behavior has received far less study than other
      care processes, the current review argues that it holds significance for the
      therapeutic relationship and influences important outcomes including
      satisfaction, adherence, and clinical outcomes of care.

PMID- 16405707
TI  - Relationship-centered care. A constructive reframing.
AB  - All illness, care, and healing processes occur in relationship--relationships of
      an individual with self and with others. Relationship-centered care (RCC) is an
      important framework for conceptualizing health care, recognizing that the nature
      and the quality of relationships are central to health care and the broader
      health care delivery system. RCC can be defined as care in which all participants
      appreciate the importance of their relationships with one another. RCC is founded
      upon 4 principles: (1) that relationships in health care ought to include the
      personhood of the participants, (2) that affect and emotion are important
      components of these relationships, (3) that all health care relationships occur
      in the context of reciprocal influence, and (4) that the formation and
      maintenance of genuine relationships in health care is morally valuable. In RCC,
      relationships between patients and clinicians remain central, although the
      relationships of clinicians with themselves, with each other and with community
      are also emphasized.

PMID- 16405709
TI  - A new theoretical foundation for relationship-centered care. Complex responsive
      processes of relating.
AB  - Relationship-centered care (RCC) is a clinical philosophy that stresses
      partnership, careful attention to relational process, shared decision-making, and
      self-awareness. A new complexity-inspired theory of human interaction called
      complex responsive processes of relating (CRPR) offers strong theoretical
      confirmation for the principles and practices of RCC, and thus may be of interest
      to communications researchers and reflective practitioners. It points out the
      nonlinear nature of human interaction and accounts for the emergence of self
      organizing patterns of meaning (e.g., themes or ideas) and patterns of relating
      (e.g., power relations). CRPR offers fresh new perspectives on the mind, self,
      communication, and organizations. For observers of interaction, it focuses
      attention on the nature of moment-to-moment relational process, the value of
      difference and diversity, and the importance of authentic and responsive
      participation, thus closely corresponding to and providing theoretical support
      for RCC.

PMID- 16405710
TI  - Complexity and healing relationships.

PMID- 16405708
TI  - The influence of information technology on patient-physician relationships.
AB  - Interpersonal relationships and information are intertwined as essential
      cornerstones of health care. Although information technology (IT) has done much
      to advance medicine, we are not even close to realizing its full potential.
      Indeed, issues related to mismanaging health information often undermine
      relationship-centered care. Information technology must be implemented in ways
      that preserve and uplift relationships in care, while accommodating major
      deficiencies in managing information and making medical decisions. Increased
      collaboration between experts in IT and relationship-centered care is needed,
      along with inclusion of relationship-based measures in informatics research.

PMID- 16405711
TI  - Organizational dimensions of relationship-centered care. Theory, evidence, and
      practice.
AB  - Four domains of relationship have been highlighted as the cornerstones of
      relationship-centered health care. Of these, clinician-patient relationships have
      been most thoroughly studied, with a rich empirical literature illuminating
      significant linkages between clinician-patient relationship quality and a wide
      range of outcomes. This paper explores the realm of clinician-colleague
      relationships, which we define to include the full array of relationships among
      clinicians, staff, and administrators in health care organizations. Building on a
      stream of relevant theories and empirical literature that have emerged over the
      past decade, we synthesize available evidence on the role of organizational
      culture and relationships in shaping outcomes, and posit a model of relationship
      centered organizations. We conclude that turning attention to relationship
      centered theory and practice in health care holds promise for advancing care to a
      new level, with breakthroughs in quality of care, quality of life for those who
      provide it, and organizational performance.

PMID- 16405713
TI  - Transglutaminases as diagnostically relevant autoantigens in patients with gluten
      sensitivity.
AB  - BACKGROUND: Patients with gluten sensitivity, i. e. celiac disease and dermatitis
      herpetiformis have anti-endomysial antibodies recognizing transglutaminases,
      which are usually detected on appropriate tissue sections. It would be desirable
      to have available a reliable, tissue-independent serological diagnostic tool. We
      compared disease-specificity and sensitivity of tTG versus eTG-based detection
      systems for the diagnosis of anti-endomysial IgA-antibodies. PATIENTS AND
      METHODS: We examined 204 serum samples in duplicates with commercial human ELISA
      kits: 54 healthy blood donors, 20 celiac disease, 29 dermatitis herpetiformis and
      101 with other autoimmune dermatoses. RESULTS: The tTG-based ELISA proved to be
      very disease-specific (100 %) and sensitive for the diagnosis of gluten
      sensitivity (95 % celiac disease; 96.6 % dermatitis herpetiformis). The eTG-based
      ELISA was also perfectly specific (100 %), but only 15 % of celiac disease-sera
      and 44.8 % of dermatitis herpetiformis-sera yielded positive results.
      CONCLUSIONS: The human tTG-ELISA fulfills all criteria of a screening test and,
      because of being investigator-independent, inexpensive and highly reproducible,
      compares favorably with the current diagnostic gold standard (indirect
      immunofluorescence and biopsy) of celiac disease and dermatitis herpetiformis.
      The low sensitivity of the eTG-ELISA may have technical reasons, but could
      theoretically also be linked to disease activity or indicate the existence of an
      as yet undefined disease subset. Studies are currently under way to address these
      issues.

PMID- 16405712
TI  - [Epidermal stem cells].
AB  - Current understanding of the biology of epidermal stem cells opens a totally new
      perspective in the function of the epidermis and adjacent epithelial structures.
      A number of pathogenetic as well as clinical-therapeutic approaches against a
      variety of dermatoses may become possible with knowledge about keratinocyte
      proliferation, differentiation and regeneration. The reservoir of epidermal stem
      cells is located in the interfollicular epidermis, the hair follicle area and the
      germinal hair follicle matrix. Endogenous stem cell clones exist here, giving
      rise to transient amplifying cells and postmitotic cells. The stem cell clones
      are organized in clusters and display high expression of adhesion proteins, which
      guarantee their stability in a specific environment consisting of different cell
      types and extracellular substrates in the stratum basale. Differentiation is
      determined by a specific cascade of chemical signals from the stem cell
      environment and from the genetic program of the cell. The clinical relevance of
      stem cells lies primarily in their therapeutic potential with reconstruction of
      epithelia by reimplantation of autologous stem cells or gene therapeutic
      applications such as targeted transfection. However, the benefit-to-risk ratio
      cannot yet be accurately estimated.

PMID- 16405714
TI  - [Anogenital dermatoses--allergic and irritative causative factors. Analysis of
      IVDK data and review of the literature].
AB  - BACKGROUND: Anogenital dermatoses (AGD) are common and often very distressing.
      Clinically it is often unclear if allergic contact dermatitis or irritant
      dermatitis is involved. In order to optimize therapy and prophylaxis, it is
      essential to identify relevant allergens or irritants. PATIENTS AND METHODS: Data
      of the Information Network of Departments of Dermatology (IVDK, data center in
      Gottingen) collected between 1999 and 2003 were analyzed. The anogenital area was
      involved in 1 168 patients with suspected allergic contact dermatitis. Clinical
      variables and patch test results were statistically compared with the remaining
      IVDK patch test population, the latter standardized for age and sex. RESULTS:
      Allergic contact dermatitis had been suspected prior to patch testing in 39.5 %,
      while in 24.6 % this diagnosis was eventually confirmed. Irritant contact
      dermatitis was diagnosed in 11.8 %. Other diagnoses, included balanitis, lichen
      sclerosus et atrophicus and herpes genitalis. Positive reactions to cinchocaine
      (6.6 %), bufexamac (3.5 %) and benzocaine (2.4 %) were observed significantly
      more often among patients with anogenital dermatitis. Among those in whom co
      factors were considered important (n = 422), wetness (38.4 %), occlusion (30.3
      %), mechanical strain (4.7 %) and heat (3.6 %) were mentioned as irritation
      factors. CONCLUSION: Because of the significantly higher frequency of
      sensitization to cinchocaine, benzocaine and bufexamac in patients with
      anogenital dermatitis, these ingredients should be used only with caution.
      According to the literature, ingredients of toiletries, cosmetics and
      contraceptives of any kind seem to cause allergic contact dermatitis rarely
      although there are several case reports. Comprehensive patch test including the
      standard series plus major sensitizers such as cinchocaine, benzocaine and
      bufexamac, and in particular patients' own skin care products, is recommended.

PMID- 16405715
TI  - A swollen face after dental surgery.

PMID- 16405716
TI  - [Dental personnel and nail designers: contact dermatitis to acrylates and
      methacrylates].

PMID- 16405717
TI  - [Pathogenesis of atopic eczema].

PMID- 16405718
TI  - [Red lobular tumor on the dorsal surface of the tongue].

PMID- 16405719
TI  - [Current regulatory aspects: ambulatory surgery and dermatology].
AB  - Recently the catalogue for ambulatory surgery in hospitals has been updated
      presenting a successful integration into the classification of EMB 2000plus. A
      fundamental reconstruction resulted in changes to the specifications of health
      care services which are covered by the catalogue. The agreement became effective
      in April 2005. According to the new catalogue for ambulatory surgery, the
      procedure codes of the OPS classification and their transitions to a specified
      EBM-figure or category are relevant for the reimbursement of ambulatory services
      provided by a hospital or in private practice. Moreover, the regulations to avoid
      unnecessary bed days of hospital care and the criteria of the German
      appropriateness evaluation protocol (G-AEP) have to be considered carefully in
      terms of inpatient admissions. In the following the revised catalogue for
      ambulatory surgery is reviewed in detail with special relevance to dermatology.

PMID- 16405720
TI  - Successful rescue therapy with tenofovir in a patient with hepatic decompensation
      and adefovir resistant HBV mutant.
AB  - BACKGROUND: Prolonged adefovir therapy exposes to the emergence of adefovir
      resistant hepatitis B virus mutants. Initial reports of the rtN236T mutation
      showed preserved sensitivity to lamivudine; however, complex mutations are
      emerging with reduced susceptibility to lamivudine. CASE PRESENTATION: After 2
      years of therapy, a cirrhotic patient developed the rtN236T and rtA181T adefovir
      resistant mutations. He had been previously treated with lamivudine, developed
      lamivudine resistance and, despite good compliance, had an incomplete response to
      adefovir. Adefovir resistance resulted in viral breakthrough with hepatitis flare
      up and liver decompensation. Tenofovir had an excellent antiviral effect allowing
      sustained control of viral replication and reversal of hepatic failure.
      CONCLUSION: In patients with cirrhosis, adefovir resistance can lead to severe
      hepatitis. Tenofovir appears to be an effective treatment of adefovir resistant
      mutants. Incomplete control of viral replication with adefovir requires
      monitoring for viral resistance and should prompt a change in antiviral
      treatment.

PMID- 16405721
TI  - Microbiology of airway disease in a cohort of patients with cystic fibrosis.
AB  - BACKGROUND: Recent reports document an increasing incidence of new Gram-negative
      pathogens such as Stenotrophomonas maltophilia and Alcaligenes xylosoxidans
      isolated from patients with Cystic Fibrosis, along with an increase in common
      Gram-negative pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia
      complex. Furthermore, the increase in multidrug-resistance of such organisms
      makes the therapeutic management of these patients more problematic. Therefore,
      careful isolation and identification, and accurate studies of susceptibility to
      antibiotics are critical for predicting the spread of strains, improving
      therapeutic measures and facilitating our understanding of the epidemiology of
      emerging pathogens. The first aim of this study was to determine the incidence
      and the prevalence of colonization by Gram-negative organisms isolated from
      respiratory samples of Cystic Fibrosis patients in the Regional Referral Cystic
      Fibrosis Centre of Naples; the second was to evaluate the spectrum of multidrug
      resistance of these organisms. METHODS: Patients (n = 300) attending the Regional
      Cystic Fibrosis Unit were enrolled in this study over 3 years. Sputum was
      processed for microscopic tests and culture. An automated system, Phoenix (Becton
      Dickinson, Sparks, Maryland, USA), was used for phenotypic identification of all
      strains; the API 20 NE identification system (bioMerieux, Marcy l'Etoile, France)
      was used when the identification with the Phoenix system was inaccurate. A PCR
      RFLP method was used to characterize the organisms in the Burkholderia cepacia
      complex. A chemosusceptibility test on microbroth dilutions (Phoenix) was used.
      Primary outcomes such as FEV1 were correlate with different pathogens. RESULTS:
      During the period of study, 40% of patients was infected by Pseudomonas
      aeruginosa, 7% by Burkholderia cepacia complex, 11% by Stenotrophomonas
      maltophilia and 7% by Alcaligenes xylosoxidans. Of the strains isolated, 460 were
      multidrug-resistant. Multiresistant were Pseudomonas aeruginosa and Burkholderia
      cepacia complex. CONCLUSION: The results confirm previously reported data; in
      particular, they show an increase the isolation of non-fermentative Gram-negative
      bacteria in Cystic Fibrosis patients. They also demonstrate increased resistance
      to antibiotics. Beta-lactams are rarely effective, with exception of ceftazidime,
      which is the most efficacious agent against multiresistant strains.
      Aminoglycosides and quinolones are poorly efficacious.

PMID- 16405722
TI  - The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely
      expressed in melanoma.
AB  - BACKGROUND: Previously we have generated the monoclonal antibody SM5-1 by using a
      subtractive immunization protocol of human melanoma. This antibody exhibits a
      high sensitivity for primary melanomas of 99% (248/250 tested) and for metastatic
      melanoma of 96% (146/151 tested) in paraffin embedded sections. This reactivity
      is superior to the one obtained by HMB-45, anti-MelanA or anti-Tyrosinase and is
      comparable to anti-S100. However, as compared to anti-S100, the antibody SM5-1 is
      highly specific for melanocytic lesions since 40 different neoplasms were found
      to be negative for SM5-1 by immunohistochemistry. The antigen recognized by SM5-1
      is unknown. METHODS: In order to characterize the antigen recognized by mAb SM5
      1, a cDNA library was constructed from the metastatic human melanoma cell line
      SMMUpos in the Uni-ZAP lambda phage and screened by mAb SM5-1. The cDNA clones
      identified by this approach were then sequenced and subsequently analyzed.
      RESULTS: Sequence analysis of nine independent overlapping clones (length 3100
      5600 bp) represent fibronectin cDNA including the ED-A, but not the ED-B region
      which are produced by alternative splicing. The 89aa splicing variant of the
      IIICS region was found in 8/9 clones and the 120aa splicing variant in 1/9
      clones, both of which are included in the CS1 region of fibronectin being
      involved in melanoma cell adhesion and spreading. CONCLUSION: The molecule
      recognized by SM5-1 is a melanoma associated FN variant expressed by virtually
      all primary and metastatic melanomas and may play an important role in melanoma
      formation and progression. This antibody is therefore not only of value in
      immunohistochemistry, but potentially also for diagnostic imaging and
      immunotherapy.

PMID- 16405723
TI  - Using relationship styles based on attachment theory to improve understanding of
      specialty choice in medicine.
AB  - BACKGROUND: Patient-provider relationships in primary care are characterized by
      greater continuity and depth than in non-primary care specialties. We
      hypothesized that relationship styles of medical students based on attachment
      theory are associated with specialty choice factors and that such factors will
      mediate the association between relationship style and ultimately matching in a
      primary care specialty. METHODS: We determined the relationship styles,
      demographic characteristics and resident specialty match of 106 fourth-year
      medical students. We assessed the associations between 1) relationship style and
      specialty choice factors; 2) specialty choice factors and specialty match, and 3)
      relationship style and specialty match. We also conducted mediation analyses to
      determine if factors examined in a specialty choice questionnaire mediate the
      association between relationship style and ultimately matching in a primary care
      specialty. RESULTS: Prevalence of attachment styles was similar to that found in
      the general population and other medical school settings with 59% of students
      rating themselves as having a secure relationship style. Patient centeredness was
      directly associated, and career rewards inversely associated with matching in a
      primary care specialty. Students with a self-reliant relationship style were
      significantly more likely to match in a non-primary care specialty as compared to
      students with secure relationship style (OR = 5.3, 95% CI 1.8, 15.6). There was
      full mediation of the association between relationship style and specialty match
      by the specialty choice factor characterized by patient centeredness. CONCLUSION:
      Assessing relationship styles based on attachment theory may be a potentially
      useful way to improve understanding and counsel medical students about specialty
      choice.

PMID- 16405724
TI  - Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome
      patients.
AB  - In a previous study we evaluated muscle blood flow and muscle metabolism in
      patients diagnosed with chronic fatigue syndrome (CFS). To better understand
      muscle metabolism in CFS, we re-evaluated our data to calculate free Magnesium
      levels in skeletal muscle. Magnesium is an essential cofactor in a number of cell
      processes. A total of 20 CFS patients and 11 controls were evaluated. Phosphorus
      magnetic resonance spectroscopy from the medial gastrocnemius muscle was used to
      calculate free Mg2+ from the concentrations and chemical shifts of Pi, PCr, and
      beta ATP peaks. CFS patients had higher magnesium levels in their muscles
      relative to controls (0.47 + 0.07 vs 0.36 + 0.06 mM, P < 0.01), although there
      was no difference in the rate of phosphocreatine recovery in these subjects, as
      reported earlier. This finding was not associated with abnormal oxidative
      metabolism as measured by the rate of recovery of phosphocreatine after exercise.
      In summary, calculation of free Mg2+ levels from previous data showed CFS
      patients had higher resting free Mg2+ levels compared to sedentary controls.

PMID- 16405725
TI  - Comprehensive analysis of the renal transcriptional response to acute uranyl
      nitrate exposure.
AB  - BACKGROUND: Chemical and radiological toxicities related to uranium acute
      exposure have been widely studied in nuclear fuel workers and military personnel.
      It is well known that uranyl nitrate induces acute renal failure (ARF). However,
      the mechanisms of this metal-induced injury are not well defined at the molecular
      level. RESULTS: Renal function and histology were assessed in mice receiving
      uranyl nitrate (UN(+)) and controls (UN(-)). To identify the genomic response to
      uranium exposure, serial analysis gene expression (SAGE) of the kidney was
      performed in both groups. Over 43,000 mRNA SAGE tags were sequenced. A selection
      of the differentially expressed transcripts was confirmed by real-time
      quantitative PCR and Western blotting. UN(+) animals developed renal failure and
      displayed the characteristic histological lesions of UN nephropathy. Of the
      >14,500 unique tags identified in both libraries, 224 had a modified expression
      level; they are known to participate in inflammation, ion transport, signal
      transduction, oxidative stress, apoptosis, metabolism, and catabolism. Several
      genes that were identified had not previously been evaluated within the context
      of toxic ARF such as translationally controlled tumor protein, insulin like
      growth factor binding protein 7 and ribosomal protein S29, all apoptosis related
      genes. CONCLUSION: We report a comprehensive description of the UN induced
      modifications in gene expression levels, including the identification of genes
      previously unrelated to ARF. The study of these genes and the metabolisms they
      control should improve our understanding of toxic ARF and enlighten on the
      molecular targets for potential therapeutic interventions.

PMID- 16405726
TI  - Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated
      Lymphoid Tissue (PALT) in the chicken.
AB  - BACKGROUND: Homeostatic trafficking of lymphocytes in the brain has important
      relevance to the understanding of CNS disease processes. The pineal gland of the
      chicken contains large accumulations of lymphocytes that suggest an important
      role related to homeostatic circadian neuro-immune interactions. The purpose of
      this initial study was to characterize the lymphocyte subsets in the pineal gland
      and quantitate the distribution and frequency of lymphocyte phenotypes at two
      time points over the 24-hour light:dark cycle. RESULTS: PALT comprised
      approximately 10% of the total pineal area. Image analysis of
      immunocytochemically stained sections showed that the majority of lymphocytes
      were CD3+ (80%) with the remaining 20% comprising B-cells and monocytes (Bu-1+),
      which tended to distribute along the periphery of the PALT. T-cell subsets in
      PALT included CD4+ (75-80%), CD8+ (20-25%), TCRalphabeta/Vbeta1+ (60%), and
      TCRgammadelta+ (15%). All of the T-cell phenotypes were commonly found within the
      interfollicular septa and follicles of the pineal gland. However, the ratios of
      CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ within the pineal tissue were
      each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and
      TCRgammadelta+/TCRalphabeta/Vbeta1+ each approximated 1:4. Bu-1+ cells were only
      rarely seen in the pineal interstitial spaces, but ramified Bu-1+
      microglia/macrophages were common in the pineal follicles. Effects of the 24-h
      light:dark cycle on these lymphocyte-pineal interactions were suggested by an
      increase in the area of PALT, a decline in the density of TCRalphabeta/Vbeta1+
      cells, and a decline in the area density of Bu-1+ microglia at the light:dark
      interphase (1900 h) compared to the dark:light interphase (0700 h). CONCLUSION:
      The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of
      neuro-immune interactions in this part of the brain. Our results further suggest
      that these interactions have a temporal component related to the 24-hour
      light:dark cycle and that CD8+ and TCRgammadelta+ T-cells are preferentially
      recruited to the pineal follicles. Pineal microglia/macrophages were common and
      represent an important candidate for mediating these lymphocyte-pineal
      interactions via secretion of cytokines and chemokines.

PMID- 16405727
TI  - Comparative evidence for a link between Peyer's patch development and
      susceptibility to transmissible spongiform encephalopathies.
AB  - BACKGROUND: Epidemiological analyses indicate that the age distribution of
      natural cases of transmissible spongiform encephalopathies (TSEs) reflect age
      related risk of infection, however, the underlying mechanisms remain poorly
      understood. Using a comparative approach, we tested the hypothesis that, there is
      a significant correlation between risk of infection for scrapie, bovine
      spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of
      lymphoid tissue in the gut. METHODS: Using anatomical data and estimates of risk
      of infection in mathematical models (which included results from previously
      published studies) for sheep, cattle and humans, we calculated the Spearman's
      rank correlation coefficient, rs, between available measures of Peyer's patch
      (PP) development and the estimated risk of infection for an individual of the
      corresponding age. RESULTS: There was a significant correlation between the
      measures of PP development and the estimated risk of TSE infection; the two age
      related distributions peaked in the same age groups. This result was obtained for
      each of the three host species: for sheep, surface area of ileal PP tissue vs
      risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density
      vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP
      tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans,
      number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition,
      when changes in exposure associated with BSE-contaminated meat were accounted
      for, the two age-related patterns for humans remained concordant: rs = 0.360 (n =
      46, P = 0.014). CONCLUSION: Our findings suggest that, for sheep, cattle and
      humans alike there is an association between PP development (or a correlate of PP
      development) and susceptibility to natural TSE infection. This association may
      explain changes in susceptibility with host age, and differences in the age
      susceptibility relationship between host species.

PMID- 16405728
TI  - Carbenoxolone does not cross the blood brain barrier: an HPLC study.
AB  - BACKGROUND: Carbenoxolone (CBX) is a widely used gap junctional blocker.
      Considering several reports indicating that transient gap junctional blockade
      could be a favourable intervention following injuries to central nervous tissue,
      and some current enthusiasm in studies using systemic injections of CBX, it is
      imperative to consider the penetration of CBX into central nervous tissue after
      systemic administrations. So far, only very indirect evidence suggests that CBX
      penetrates into the central nervous system after systemic administrations. We
      thus determined the amounts of CBX present in the blood and the cerebrospinal
      fluid of rats after intraperitoneal administration, using high performance liquid
      chromatography. RESULTS: CBX was found in the blood of the animals, up to 90
      minutes post-injection. However, the cerebrospinal fluid concentration of CBX was
      negligible. CONCLUSION: Thus, we conclude that, most likely, CBX does not
      penetrate the blood brain barrier and therefore recommend careful consideration
      in the manner of administration, when a central effect is desired.

PMID- 16405729
TI  - Council tax valuation band predicts breast feeding and socio-economic status in
      the ALSPAC study population.
AB  - BACKGROUND: Breast-feeding rates in the UK are known to vary by maternal socio
      economic status but the latter function is imperfectly defined. We test if CTVB
      (Council Tax Valuation Band - a categorical assessment of UK property values and
      amenities governing local tax levies) of maternal address predicts, in a large UK
      regional sample of births, (a) breast-feeding (b) personal and socio-economic
      attributes of the mothers. METHODS: Retrospective study of a subset (n.1390
      selected at random) of the ALSPAC sample (Avon Longitudinal Study of Parents and
      Children), a large, geographically defined cohort of mothers followed from early
      pregnancy to 8 weeks post-delivery. Outcome measures are attitudes to breast
      feeding prior to delivery, breast-feeding intention and uptake, demographic and
      socio-economic attributes of the mothers, CTVB of maternal home address at the
      time of each birth. Logistic regression analysis, categorical tests. RESULTS: 
      STUDY SAMPLE: 1360 women divided across the CTVBs--at least 155 in any band or
      band aggregation. CTVB predicted only one belief or attitude--that bottle-feeding
      was more convenient for the mother. However only 31% of 'CTVB A infants' are
      fully breast fed at 4 weeks of life whereas for 'CTVB E+ infants' the rate is
      57%. CTVB is also strongly associated with maternal social class, home
      conditions, parental educational attainment, family income and smoking habit.
      CONCLUSION: CTVB predicts breast-feeding rates and links them with social
      circumstances. CTVB could be used as the basis for accurate resource allocation
      for community paediatric services: UK breast-feeding rates are low and merit
      targeted promotion.

PMID- 16405730
TI  - Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and
      neck paraganglioma and familial paraganglioma and/or pheochromocytoma.
AB  - BACKGROUND: Germline mutations of the SDHD, SDHB and SDHC genes, encoding three
      of the four subunits of succinate dehydrogenase, are a major cause of hereditary
      paraganglioma and pheochromocytoma, and demonstrate that these genes are classic
      tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex
      and a component of both the Krebs cycle and the mitochondrial respiratory chain
      (succinate:ubiquinone oxidoreductase or complex II). METHODS: Using conformation
      sensitive gel electrophoresis (CSGE) and direct DNA sequencing to analyse genomic
      DNA from peripheral blood lymphocytes, here we describe the mutation analysis of
      the SDHB and SDHC genes in 37 patients with sporadic (i.e. no known family
      history) head and neck paraganglioma and five pheochromocytoma and/or
      paraganglioma families. RESULTS: Two sporadic patients were found to have a SDHB
      splice site mutation in intron 4, c.423+1G>A, which produces a mis-spliced
      transcript with a 54 nucleotide deletion, resulting in an 18 amino acid in-frame
      deletion. A third patient was found to carry the c.214C>T (p.Arg72Cys) missense
      mutation in exon 4 of SDHC, which is situated in a highly conserved protein motif
      that constitutes the quinone-binding site of the succinate: ubiquinone
      oxidoreductase (SQR) complex in E. coli. Together with our previous results, we
      found 27 germline mutations of SDH genes in 95 cases (28%) of sporadic head and
      neck paraganglioma. In addition all index patients of five families showing
      hereditary pheochromocytoma-paraganglioma were found to carry germline mutations
      of SDHB: four of which were novel, c.343C>T (p.Arg115X), c.141G>A (p.Trp47X),
      c.281G>A (p.Arg94Lys), and c.653G>C (p.Trp218Ser), and one reported previously,
      c.136C>T, p.Arg46X. CONCLUSION: In conclusion, these data indicate that germline
      mutations of SDHB and SDHC play a minor role in sporadic head and neck
      paraganglioma and further underline the importance of germline SDHB mutations in
      cases of familial pheochromocytoma-paraganglioma.

PMID- 16405731
TI  - Management and outcome of bleeding pseudoaneurysm associated with chronic
      pancreatitis.
AB  - BACKGROUND: A bleeding pseudoaneurysm in patients with chronic pancreatitis is a
      rare and potentially lethal complication. Optimal treatment of bleeding
      peripancreatic pseudoaneurysm remains controversial. This study reports on
      experience at Chang Gung Memorial Hospital (CGMH) in managing of bleeding
      pseudoaneurysms associated with chronic pancreatitis. METHODS: The medical
      records of 9 patients (8 males and 1 female; age range, 28-71 years; median, 36
      years) with bleeding pseudoaneurysms associated with chronic pancreatitis treated
      at CGMH between Aug. 1992 and Sep. 2004 were retrospectively reviewed. Alcohol
      abuse (n = 7;78%) was the predominant predisposing factor. Diagnoses of bleeding
      pseudoaneurysms were based on angiographic (7/7), computed tomographic (4/7),
      ultrasound (2/5), and surgical (2/2) findings. Whether surgery or angiographic
      embolization was performed was primarily based on patient clinical condition.
      Median follow-up was 38 months (range, 4-87 months). RESULTS: Abdominal computed
      tomography revealed bleeding pseudoaneurysms in 4 of 7 patients (57%).
      Angiography determined correct diagnosis in 7 patients (7/7, 100%). The splenic
      artery was involved in 5 cases, the pancreaticoduodenal artery in 2, the
      gastroduodenal artery in 1, and the middle colic artery in 1. Initial treatment
      was emergency (n = 4) or elective (n = 3) surgery in 7 patients and arterial
      embolization in 2. Rebleeding was detected after initial treatment in 3 patients.
      Overall, 5 arterial embolizations and 9 surgical interventions were performed;
      the respective rates of success of these treatments were 20% (1/5) and 89% (8/9).
      Five patients developed pseudocysts before treatment (n = 3) or following
      intervention (n = 2). Pseudocyst formation was identified in 2 of the 3
      rebleeding patients. Five patients underwent surgical treatment for associated
      pseudocysts and bleeding did not recur. One patient died from angiography-related
      complications. Overall mortality rate was 11% (1/9). Surgery-related mortality
      was 0%. CONCLUSION: Angiography is valuable in localizing bleeding
      pseudoaneurysms. In this limited series, patients with bleeding pseudoaneurysms
      associated with chronic pancreatitis treated surgically seemingly obtained good
      outcomes.

PMID- 16405732
TI  - Structural and functional properties of genes involved in human cancer.
AB  - BACKGROUND: One of the main goals of cancer genetics is to identify the causative
      elements at the molecular level leading to cancer. RESULTS: We have conducted an
      analysis of a set of genes known to be involved in cancer in order to unveil
      their unique features that can assist towards the identification of new candidate
      cancer genes. CONCLUSION: We have detected key patterns in this group of genes in
      terms of the molecular function or the biological process in which they are
      involved as well as sequence properties. Based on these features we have
      developed an accurate Bayesian classification model with which human genes have
      been scored for their likelihood of involvement in cancer.

PMID- 16405734
TI  - Randomized controlled trial comparing four strategies for delivering e-curriculum
      to health care professionals [ISRCTN88148532].
AB  - BACKGROUND: Internet education is increasingly provided to health professionals,
      but little is known about the most effective strategies for delivering the
      content. The purpose of this study is to compare four strategies for delivering
      an Internet-based (e-) curriculum on clinicians' knowledge (K), confidence
      (CONF), and communication (COMM) about herbs and other dietary supplements (HDS).
      METHODS: This national randomized 2 x 2 factorial trial included physicians,
      pharmacists, nurses, nutritionists and trainees in these fields. Participants
      were randomly assigned to one of four curriculum delivery strategies for 40 brief
      modules about HDS: a) delivering four (4) modules weekly over ten (10) weeks by
      email (drip-push); b) modules accessible on web site with 4 reminders weekly for
      10 weeks (drip-pull); c) 40 modules delivered within 4 days by email (bolus
      push); and d) 40 modules available on the Internet with one email informing
      participants of availability (bolus-pull). RESULTS: Of the 1,267 enrollees, 25%
      were male; the average age was 40 years. The completion rate was 62%, without
      significant differences between delivery groups. There were statistically
      significant improvements in K, CONF and COMM scores after the course (P<0.001 for
      all), although the difference in COMM was small. There were no significant
      differences in any of the three outcomes by delivery strategy, but outcomes were
      better for those who paid for continuing education credit. CONCLUSION: All
      delivery strategies tested similarly improved K, CONF, COMM scores about HDS.
      Educators can use the strategy that is most convenient without diminishing
      effectiveness. Additional curricula may be necessary to make substantial changes
      in clinicians' communication practices.

PMID- 16405733
TI  - The carcinogenic potential of tacrolimus ointment beyond immune suppression: a
      hypothesis creating case report.
AB  - BACKGROUND: Since tacrolimus ointment was approved by the U.S. Food and Drug
      Administration (FDA) as a promising treatment for atopic dermatitis, it has been
      approved in more than 30 additional countries, including numerous European Union
      member nations. Moreover, in the current clinical routine the use of this drug is
      no longer restricted to the approved indication, but has been extended to a wide
      variety of inflammatory skin diseases including some with the potential of
      malignant transformation. So far, the side-effects reported from the topical use
      of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema).
      Recently, however, the FDA reviewed the safety of topical tacrolimus, which
      resulted in a warning that the use of calcineurin inhibitors may be associated
      with an increased risk of cancer. CASE PRESENTATION: Oral lichen planus (OLP) was
      diagnosed in a 56-year-old women in February 1999. After several ineffective
      local and systemic therapeutic measures an off-label treatment of this
      recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002.
      After a few weeks of treatment most of the lesions ameliorated, with the
      exception of the plaques on the sides of the tongue. Nevertheless, the patient
      became free of symptoms which, however, reoccurred once tacrolimus was weaned, as
      a consequence treatment was maintained. In April 2005, the plaques on the left
      side of the tongue appeared increasingly compact and a biopsy specimen confirmed
      the suspected diagnosis of an oral squamous cell carcinoma. CONCLUSION: The
      suspected causal relationship between topical use of tacrolimus and the
      development of a squamous cell carcinoma prompted us to test the notion that the
      carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end,
      tacrolimus has been shown to have an impact on cancer signalling pathways such as
      the MAPK and the p53 pathway. In the given case, we were able to demonstrate that
      these pathways had also been altered subsequent to tacrolimus therapy.

PMID- 16405735
TI  - An improved procedure for gene selection from microarray experiments using false
      discovery rate criterion.
AB  - BACKGROUND: A large number of genes usually show differential expressions in a
      microarray experiment with two types of tissues, and the p-values of a proper
      statistical test are often used to quantify the significance of these
      differences. The genes with small p-values are then picked as the genes
      responsible for the differences in the tissue RNA expressions. One key question
      is what should be the threshold to consider the p-values small. There is always a
      trade off between this threshold and the rate of false claims. Recent statistical
      literature shows that the false discovery rate (FDR) criterion is a powerful and
      reasonable criterion to pick those genes with differential expression. Moreover,
      the power of detection can be increased by knowing the number of non-differential
      expression genes. While this number is unknown in practice, there are methods to
      estimate it from data. The purpose of this paper is to present a new method of
      estimating this number and use it for the FDR procedure construction. RESULTS: A
      combination of test functions is used to estimate the number of differentially
      expressed genes. Simulation study shows that the proposed method has a higher
      power to detect these genes than other existing methods, while still keeping the
      FDR under control. The improvement can be substantial if the proportion of true
      differentially expressed genes is large. This procedure has also been tested with
      good results using a real dataset. CONCLUSION: For a given expected FDR, the
      method proposed in this paper has better power to pick genes that show
      differentiation in their expression than two other well known methods.

PMID- 16405736
TI  - Local protein structure prediction using discriminative models.
AB  - BACKGROUND: In recent years protein structure prediction methods using local
      structure information have shown promising improvements. The quality of new fold
      predictions has risen significantly and in fold recognition incorporation of
      local structure predictions led to improvements in the accuracy of results. We
      developed a local structure prediction method to be integrated into either fold
      recognition or new fold prediction methods. For each local sequence window of a
      protein sequence the method predicts probability estimates for the sequence to
      attain particular local structures from a set of predefined local structure
      candidates. The first step is to define a set of local structure representatives
      based on clustering recurrent local structures. In the second step a
      discriminative model is trained to predict the local structure representative
      given local sequence information. RESULTS: The step of clustering local
      structures yields an average RMSD quantization error of 1.19 A for 27 structural
      representatives (for a fragment length of 7 residues). In the prediction step the
      area under the ROC curve for detection of the 27 classes ranges from 0.68 to
      0.88. CONCLUSION: The described method yields probability estimates for local
      protein structure candidates, giving signals for all kinds of local structure.
      These local structure predictions can be incorporated either into fold
      recognition algorithms to improve alignment quality and the overall prediction
      accuracy or into new fold prediction methods.

PMID- 16405737
TI  - Review of "the Twelfth West Coast Retrovirus Meeting" and "the Twenty-third
      Annual Symposium on Nonhuman Primate Models for AIDS".
AB  - Two recent meetings held on the west coast of the USA highlighted current work
      being done in the field of retrovirology and AIDS. The meetings, "The Twelfth
      West Coast Retrovirus Meeting" (Palm Springs CA; October 6-8, 2005), and the
      "Twenty-third Annual Symposium on Nonhuman Primate Models for AIDS" (Portland OR;
      September 21-24) covered a broad range of topics. The highlights covered here are
      not meant to be inclusive but reflect presentations of interest in the
      identification and development of new HIV therapies and the role played by animal
      models in their development.

PMID- 16405738
TI  - Mapping of panda plumage color locus on the microsatellite linkage map of the
      Japanese quail.
AB  - BACKGROUND: Panda (s) is an autosomal recessive mutation, which displays overall
      white plumage color with spots of wild-type plumage in the Japanese quail
      (Coturnix japonica). In a previous study, the s locus was included in the same
      linkage group as serum albumin (Alb) and vitamin-D binding protein (GC) which are
      mapped on chicken (Gallus gallus) chromosome 4 (GGA4). In this study, we mapped
      the s locus on the microsatellite linkage map of the Japanese quail by linkage
      analysis. RESULTS: Segregation data on the s locus were obtained from three
      generation families (n = 106). Two microsatellite markers derived from the
      Japanese quail chromosome 4 (CJA04) and three microsatellite markers derived from
      GGA4 were genotyped in the three-generation families. We mapped the s locus
      between GUJ0026 and ABR0544 on CJA04. By comparative mapping with chicken, this
      locus was mapped between 10.0 Mb and 14.5 Mb region on GGA4. In this region, the
      endothelin receptor B subtype 2 gene (EDNRB2), an avian-specific paralog of the
      mammalian endothelin receptor B gene (EDNRB), is located. Because EDNRB is
      responsible for aganglionic megacolon and spot coat color in mouse, rat and
      equine, EDNRB2 is suggested to be a candidate gene for the s locus. CONCLUSION:
      The s locus and the five microsatellite markers were mapped on CJA04 of the
      Japanese quail. EDNRB2 was suggested to be a candidate gene for the s locus.

PMID- 16405740
TI  - [Transformation of attached cells derived from fetal umbilical cord blood induced
      by conditional medium of hepatoma cells].
AB  - BACKGROUND & OBJECTIVE: Stem cells derived from fetal umbilical cord blood are of
      undifferentiated at early stage. They are sensitive to stimulations from the
      environment, and may be transformed under the effects of carcinogenic factors.
      This study was to explore the sensitivity of stem cells derived from fetal
      umbilical cord blood to carcinogenic factors. METHODS: Mononuclear cells were
      isolated from fetal umbilical cord blood, and the attached cells were cultured in
      the medium containing 10% conditional medium of HepG2 hepatoma cells. A new cell
      line was gained, termed H-UCB. The biological features of H-UCB cells were
      detected by electron microscopy, karyotype analysis, cell cytometry, Western
      blot, and colony formation assay. RESULTS: H-UCB cells proliferated faster after
      passage 3. The cells were fibroblast-like and hepatocyte-like, with the ratio of
      nucleus to cytoplasm increased. Under electron microscope, many microvilli on the
      surface and numbers of vacuoles in the cytoplasm of the cells were observed, the
      nuclei were large and irregular, endocytosis phenomena were noticed. Karyotype
      analysis indicated that the cells were heteroploid, and the number of chromosomes
      was between 50 and 70. Flow cytometry data indicated that the proliferation
      period was 22.9 h, and the karyotype was between diploid and tetraploid. Western
      blot showed that c-Myc protein and proliferating cell nuclear antigen (PCNA) were
      overexpressed in H-UCB cells. According to flow cytometry, the positive rates of
      surface markers of H-UCB cells were 79.0% for CD105, 1.2% for CD34, and 12.2% for
      CD106; those of control HepG2 cells were 15.0% for CO105, 9.8% for CD34, and 1.4%
      for CD106. The colony formation rate of H-UCB cells in soft agar was (13.2+/
      2.6)%. CONCLUSION: H-UCB cells are derived from endothelial cells, and are
      transformed as malignant cells with tumor cell characteristics.

PMID- 16405739
TI  - Receptor Ck-dependent signaling regulates hTERT gene transcription.
AB  - BACKGROUND: Available evidence suggests that the regulation of telomerase
      activity primarily depends on the transcriptional control of the human telomerase
      reverse transcriptase (hTERT) gene. Although several activators and repressors of
      hTERT gene transcription have been identified, the exact mechanism by which hTERT
      transcription is repressed in normal cells and activated in cancer cells remains
      largely unknown. In an attempt to identify possible novel mechanisms involved in
      the regulation of hTERT transcription, the present study examined the role of
      Receptor Ck, a cell surface receptor specific for cholesterol, in the
      transcription of hTERT gene in normal human peripheral blood mononuclear cells.
      RESULTS: Activated Receptor Ck was found to down-regulate hTERT mRNA expression
      by repressing the transcription of c-myc gene. Receptor Ck-dependent signaling
      was also found to down-regulate the mRNA expression of the gene coding for the
      ligand inducible transcription factor, peroxisome proliferator-activated receptor
      gamma (PPARgamma). The ligand activation of PPARgamma resulted in the down
      regulation of c-myc and hTERT mRNA expression. By using specific activator and
      inhibitor of protein kinase C (PKC), it was demonstrated that Receptor Ck
      dependent down-regulation of hTERT gene transcription involved inhibition of PKC.
      In addition, 25-hydroxycholesterol was found to contribute to the transcriptional
      regulation of hTERT gene. CONCLUSION: Taken together, the findings of this study
      present evidence for a molecular link between cholesterol-activated Receptor Ck
      and hTERT transcription, and provide new insights into the regulation of hTERT
      expression in normal human peripheral blood mononuclear cells.

PMID- 16405741
TI  - [Correlation of genetic polymorphisms in DNA repair genes ADPRT and XRCC1 to risk
      of gastric cancer].
AB  - BACKGROUND & OBJECTIVE: Adenosine diphosphate ribosyl transferase (ADPRT) and X
      ray repair cross-complementing 1 (XRCC1) are 2 major DNA base excision repair
      (BER) proteins and act interactively in stimulating and executing BER processes.
      Polymorphisms of ADPRT 762Val-->Ala and XRCC1 399Arg-->Gln have been verified to
      associate with altered protein function and BER activity. This study was to
      examine the contribution of these 2 polymorphisms, alone or in combination, to
      the risk of developing gastric cancer. METHODS: A total of 236 patients with
      gastric cancer and 708 cancer-free controls were genotyped for the 2
      polymorphisms by polymerase chain reaction-restrictive fragment length
      polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI)
      were calculated using unconditional logistic regression model to evaluate the
      impact of these 2 polymorphisms on the risk of developing gastric cancer.
      RESULTS: The subjects having the ADPRT Ala/Ala genotype had an OR of 2.07 (95%
      CI=1.33-3.21; P=0.001) compared with those having the Val/Val genotype. Gene-gene
      interaction of ADPRT and XRCC1 polymorphisms increased the risk of gastric cancer
      in a super-multiplicative manner, with an OR of 5.32 (95% CI=1.12-28.57) for the
      presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, although the
      XRCC1 polymorphism itself was not associated with the risk of gastric cancer.
      CONCLUSION: The ADPRT 762Val-->Ala polymorphism plays an important role in the
      development of gastric cancer, and the XRCC1 399Arg-->Gln polymorphism may serve
      as a risk modifier.

PMID- 16405742
TI  - [Inhibitory effect of silencing hTERT gene by short hairpin RNA on growth of
      human laryngeal squamous cell carcinoma xenograft in nude mice].
AB  - BACKGROUND & OBJECTIVE: RNA interference (RNAi) is triggered by the presence of
      double-stranded RNA (dsRNA) in the cell and results in rapid destruction and post
      transcriptional gene silencing of target mRNA. The roles of RNAi in gene function
      and antiviral therapy have been reported, but its effect on human telomerase
      reverse transcriptase (hTERT) gene, which is highly expressed in laryngeal
      squamous cell carcinoma and other head and neck neoplasms, has seldom been
      reported. This study was to explore the inhibitory effect of silencing hTERT gene
      by short hairpin RNA (shRNA) on growth of laryngeal squamous cell carcinoma
      xenograft in nude mice with RNAi technique. METHODS: Plasmid pshRNA containing
      fluorescein gene and hTERT cDNA sequences was synthesized. Human laryngeal
      squamous cell carcinoma Hep-2 cells were transplanted into nude mice to establish
      xenograft tumors. pshRNA was transfected into the tumors. The tumor volume was
      observed. Fluorescence expression in the tumors was observed by laser confocal
      microscopy. Tumor morphology was observed with HE staining. Cell apoptosis was
      detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) assay. The expression of hTERT protein in the tumors was detected by SP
      immunohistochemistry. The structural change of heart, liver, kidney and spleen
      was observed, and peripheral blood hematological and biochemical parameters were
      determined. RESULTS: The tumor volume was significantly smaller in pshRNA group
      than in normal saline (NS) group and blank plasmid group (P<0.01). The inhibition
      rate was 76.50% in pshRNA group. After transfection of pshRNA or blank plasmid,
      many green fluorescent cells were observed under confocal microscope. The
      necrosis and apoptosis of tumor cells were found under light microscope in shRNA
      group. The apoptotic index of tumor cells was significantly higher in pshRNA
      group than in NS group and blank plasmid group [(26.47+/-4.25)% vs. (2.73+/
      1.35)% and (3.40+/-1.41)%, P<0.05]. pshRNA directly down-regulated hTERT protein
      expression in the tumors, but did no damage to the heart, liver, kidney, spleen,
      and blood system of nude mice. CONCLUSION: shRNA plasmid containing specific
      sequences of hTERT gene could significantly inhibit the growth of laryngeal
      carcinoma in nude mice, with no side effect on the heart, liver, kidney, spleen,
      and blood system.

PMID- 16405743
TI  - [Mechanism of opening of mitochondrial permeability transition pore induced by
      arsenic trioxide].
AB  - BACKGROUND & OBJECTIVE: Permeability transition pore (PTP) is central for
      apoptosis by acting as a good candidate pathway for the release of cytochrome c
      and apoptosis-induction factors from mitochondria. Arsenite may induce apoptosis
      via a direct effect on PTP. To characterize the exact mechanism for arsenite to
      induce PTP opening, the correlations of calcium-induced calcium release from
      mitochondria (mCICR) to As2O3-induced PTP opening and cytochrome c release from
      mitochondria were studied. METHODS: Mitochondria were prepared from Wistar rat
      livers. The effect of As2O3 on mitochondrial PTP opening was measured with
      ultraviolet (UV) spectrophotometer. The changes of Ca(2+) concentration were
      detected with UV spectrophotometer to monitor Ca(2+) -induced Ca(2+) release from
      mitochondria. Cytochrome c release mediated by Ca(2+) was measured with Western
      blot. RESULTS: As2O3 (10 micromol/L) combined with low concentration of Ca(2+)
      didn't induce PTP opening and cytochrome c release from mitochondria; while As2O3
      (10 micromol/L) combined with high concentration of Ca(2+) induced PTP opening
      and cytochrome c release. When mCICR was inhibited, the effect of As2O3 and
      Ca(2+) on PTP opening and cytochrome c release was completely inhibited.
      CONCLUSION: As2O3-induced PTP opening and cytochrome c release depend on mCICR.

PMID- 16405744
TI  - [Analysis of differential proteins in laryngeal carcinoma cell line Hep-2 with
      transfection of LCRG1].
AB  - BACKGROUND & OBJECTIVE: Laryngeal carcinoma-related gene 1 (LCRG1), a novel
      laryngeal carcinoma-related tumor suppressor gene, was cloned with mRNA
      differential display method. Previous researches showed LCRG1 might inhibit cell
      growth, proliferation, colony formation in soft agar, and tumorigenesis of
      laryngeal carcinoma cell line Hep-2. This study was to screen the proteins
      associated with the tumor suppressive function of LCRG1 by comparative proteomics
      method. METHODS: The whole cellular proteins of Hep-2/LCRG1 and Hep-2/pcDNA3.1(+)
      cells were extracted and separated by two-dimensional gel electrophoresis (2-DE)
      technology. After electrophoresis, the gels were stained by Coomassie Brilliant
      Blue G-250, and analyzed using PDQuest software. The differentially expressed
      proteins were cut from the gels, analyzed by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), or
      electrospray ionization-quadrupole time-of-flight MS/MS (ESI-Q-TOF MS/MS), and
      identified through searching database with Mascot software. RESULTS: The well
      resolved, reproducible 2-DE patterns of Hep-2/LCRG1 and Hep-2/pcDNA3.1(+) cells
      were established. The total protein spots were 1,075+/-43 in Hep-2/LCRG1 cells
      and 1,027+/-23 in Hep-2/pcDNA3.1(+) cells, with an average matching rate of 91%.
      Using mass spectrometry technology, 20 differential protein spots between the 2
      cell lines were identified. Among them, 16 were identified by MALDI-TOF-MS, and 4
      were identified by ESI-Q-TOF MS/MS. Some of the identified proteins were
      characterized as members of cellular transcription and metabolism enzymes.
      CONCLUSIONS: In this study, 2-DE gels of Hep-2/LCRG1 cell line with high
      expression of LCRG1 mRNA and vector control Hep-2/pcDNA3.1(+) cell line were
      established; some differential proteins related to LCRG1 were identified by mass
      spectrometry. These data will help to illustrate the molecular mechanism of
      LCRG1.

PMID- 16405745
TI  - [In vitro purging effect of CD3AK/iNOS on leukemia cells].
AB  - BACKGROUND & OBJECTIVE: LAK cells have been applied to purge minimal residual
      leukemia cells in allogeneic hematopoietic stem cell transplantation(AHSCT) in
      clinic practice. CD3AK cells belong to T lymphocytes activated by anti-CD3McAb.
      This study was to construct nitric oxide donor CD3AK/iNOS through transfecting
      inducible nitric oxide synthase (iNOS) gene into human CD3AK cells by retroviral
      vector, and investigate the cytotoxic activity of CD3AK/iNOS to leukemia cell
      lines K562 and K562/ADM. METHODS: The amphotropic packaging cell line PA317
      transfected with iNOS gene was cultivated to obtain viral supernatant. Human
      peripheral blood mononuclear cells (PBMNCs) were isolated and activated by anti
      CD3McAb and low dose of interleukin-2 (IL-2). CD3AK cells were incubated with
      viral supernatant. The amount of nitric oxide (NO) and the activity of iNOS in
      the cultured supernatant of CD3AK/iNOS were evaluated. The cytotoxic activities
      of CD3AK/iNOS and CD3AK cells to K562 and K562/ADM cells were evaluated by MTT
      assay. RESULTS: The contents of NO excreted by CD3AK/iNOS and CD3AK cells were
      (378.60+/-41.57) micromol/L and (98.07+/-22.31) micromol/L, respectively
      (P<0.001); the activities of iNOS synthesized by CD3AK/iNOS and CD3AK cells were
      (20.77+/-2.49) U/ml and (9.81+/-1.96) U/ml, respectively (P<0.001). The cytotoxic
      activities of CD3AK/iNOS cells to K562 and K562/ADM cells were significantly
      stronger than those of CD3AK [(64.85+/-18.13)% vs. (45.66+/-17.46)%, P<0.05;
      (63.80+/-9.93)% vs. (47.85+/-12.01)%, P<0.05]. CONCLUSIONS: The content of NO and
      activity of iNOS synthesized and excreted by CD3AK/iNOS cells are largely
      increased compared with those of CD3AK cells. CD3AK/iNOS cells have more
      significant cytotoxic activity to K562 and K562/ADM cells than CD3AK cells, but
      its cytotoxic activities to K562 and K562/ADM cells are similar.

PMID- 16405746
TI  - [Impact of radiofrequency on splenocyte immunity of mice bearing H22 liver
      cancer].
AB  - BACKGROUND & OBJECTIVE: Radiofrequency (RF) can destroy local tumor tissue with
      less damage to the intervening tissue. The effect of RF on immune function of
      tumor-bearing body needs to be further investigated. This study was designed to
      evaluate the impact of RF on splenocyte immunity of mice bearing H22 liver cancer
      through detecting splenocyte proliferation, cytotoxicity, and expression pattern
      of cytokines T helper type 1 (Th1)/Th2. METHODS: A total of 24 BALB/c mice were
      randomized into 4 groups: RF, surgical resection, tumor-bearing control, and
      normal control groups. The proliferation of splenocytes was detected by MTT
      assay, and the cytotoxicity of splenocytes was assayed by double-color flow
      cytometry (FCM). The concentrations of interferon-gamma (IFN-gamma), interleukin
      2 (IL-2), IL-4, and IL-10 in splenocyte culture supernatants were detected by
      enzyme-linked immunoabsorbent assay (ELISA), and mRNA levels of the cytokines in
      splenocytes were assayed by reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: The proliferation of splenocytes and mortality of H22 cells were
      significantly higher in RF group than in surgical resection group, normal control
      group, and tumor-bearing group (P<0.05). The concentration and mRNA level of IL-2
      and IFN-gamma were significantly higher in RF group than in surgical resection
      group, normal control group, and tumor-bearing group (P<0.05); the concentration
      and mRNA level of IL-4 and IL-10 were significantly lower in RF group than in
      surgical resection group, normal control group, and tumor-bearing group (P<0.05).
      No significant difference were found between surgical resection group and normal
      control group (P>0.05). CONCLUSIONS: RF can efficiently stimulate splenocyte
      activation and proliferation in H22-bearing mice, and enhance splenocyte
      cytotoxicity to tumor cells. RF could facilitate the secretion and gene
      transcription of Th1 type cytokines in H22 cells.

PMID- 16405747
TI  - [Inhibitory effect of bcl-2 antisense oligodeoxynucleotides on growth of human
      lung carcinoma xenograft in nude mice].
AB  - BACKGROUND & OBJECTIVE: Antisense oligodeoxynucleotides (ASODN) targeting bcl-2
      have in vitro and in vivo antitumor activities. We have identified a novel
      antisense sequence in the coding region of bcl-2 mRNA that could enhance
      chemosensitivity and radiosensitivity of leukemia cells and lung carcinoma cells.
      This study was designed to investigate inhibitory effects of bcl-2 ASODN on
      development and growth ability of human lung carcinoma NCI-H460 cells xenograft
      in nude mice. METHODS: bcl-2 ASODN was added to NCI-H460 cells. Inhibitory rate
      of cell growth was assayed by MTT assay. bcl-2 ASODN-treated NCI-H460 cells were
      implanted subcutaneously into nude mice to observe tumor growth and calculate
      tumor inhibitory rate. Seven days after subcutaneous implantation of untreated
      NCI-H460 cells, the tumor-bearing mice were randomized into 3 groups: control
      group, ASODN group, and nonsense oligodeoxynucleotides (NSODN) group. bcl-2
      ASODN, bcl-2 NSODN, and saline were separately injected into the tumor bodies of
      mice in relevant groups for 3 week. The tumor weight and volume were measured,
      and the morphology of tumor cells was observed under microscope. RESULTS: bcl-2
      ASODN reduced the growth of NCI-H460 cells in a time-dependent manner. Inhibitory
      rate of NCI-H460 cells was significantly higher in bcl-2 ASODN group than in bcl
      2 NSODN group (P<0.05). The tumorigenic ability of NCI-H460 cells was reduced by
      bcl-2 ASODN, with the maximum tumor growth inhibitory rate of 87.5% (P<0.01). The
      tumor formation time was prolonged to 12.6 days. Tumor growth was significantly
      inhibited in bcl-2 ASODN group as compared with that in NSODN group and control
      group(P<0.01). The tumor weight was significantly lighter in bcl-2 ASODN group
      than in bcl-2 NSODN group and control group (P<0.01). The growth inhibitory rate
      was 71.0% in bcl-2 ASODN group. Serious necrosis foci and inflammatory cell
      infiltration were observed in tumor tissues of bcl-2 ASODN group, while cancer
      cells were diffused in tumor tissues of bcl-2 NSODN group and control group.
      CONCLUSION: bcl-2 ASODN can suppress tumorigenic ability of NCI-H460 cells and
      inhibit tumor growth in nude mice.

PMID- 16405748
TI  - [Radioresistant subline of human glioma cell line MGR2R induced by repeated high
      dose X-ray irradiation].
AB  - BACKGROUND & OBJECTIVE: Radiotherapy is one of the most important adjuvant
      treatments for patients with malignant glioma, but radiosensitivities of gliomas
      are widely various. This study was to induce human glioma cell line MGR2 to
      become a stable radioresistant cell subline, and investigate the mechanisms of
      radioresistance. METHODS: Human glioma cell line MGR2, with survival fraction of
      2 Gy (SF(2)) of 0.18+/-0.05, was irradiated by intermittent high dose X-ray (2 Gy
      for 3 times, 5 Gy for 2 times). After each irradiation, the cells were cultured
      for 5 to 8 weeks and received irradiation again. The whole process of irradiation
      and culture lasted for 11 months. The cells derived from MGR2 were obtained and
      named MGR2R (MGR2 radiation induction). Double times of MGR2 and MGR2R cells were
      determined by MTT assay. Dose-survival curves, radiobiological parameters and SF2
      were determined by colony-forming assay and line-quadratic model. The variation
      of their cell cycles was investigated by flow cytometry and cell cycle
      synchronization of serum-starvation. RESULTS: The double time of MGR2 cells was
      3.6 days, while that of MGR2R cells was 4.0 days. The growth rate of MGR2R cells
      was slower than that of MGR2 cells. Using colony-forming assay and line-quadratic
      model, the parameters of MGR2 and MGR2R were obtained. The alpha values of MGR2
      and MGR2R were 0.447 and 0.089 (t=4.524, P=0.011), the beta values were 0.177 and
      0.141 (t=1.562, P=0.193), and the SF(2) were 0.208 and 0.478 (t=-6.062, P=0.040),
      respectively. The radioresistance of MGR2R cells was stronger than that of MGR2
      cells. The distribution of cell cycle in MGR2 cells after synchronization were
      54.8% in G(1) phase, 30.9% in S phase, and 14.3% in G(2) phase; 24 h after loss
      of synchronization, the distribution of cell cycle were 35.9% in G(1) phase,
      51.2% in S phase, and 12.8% in G(2) phase. The distribution of cell cycle in
      MGR2R cells after synchronization were 55.7% in G(1) phase, 27.8% in S phase, and
      16.6% in G(2) phase; 24 h after loss of synchronization, the distribution of cell
      cycle were 56.4% in G1 phase, 26.7% in S phase, and 16.9% in G(2) phase. MGR2R
      cells appeared G(2) phase arrest before synchronization, and G1 phase arrest
      after loss of synchronization. CONCLUSIONS: After intermittent high dose X-ray
      irradiation, radiosensitive cell line MGR2 has been induced to be relatively
      radioresistant (MGR2R). MGR2R cells grow slower and have G(1) phase and G(2)
      phase arrest which might relate to its radioresistance.

PMID- 16405750
TI  - [Correlation of Skp2 expression in gastric carcinoma to expression of P27 and
      PTEN].
AB  - BACKGROUND & OBJECTIVE: S-phase kinase-associated protein 2 (Skp2) is a positive
      regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of
      cyclin-dependent kinase inhibitor P27. Its overexpression has been involved in
      cell transformation and tumorigenesis. This study was to investigate the
      significance of Skp2 expression in human gastric carcinoma and its correlation to
      expression of both P27 and PTEN. METHODS: The expression of Skp2 in 138 specimens
      of gastric cancer and their paired adjacent mucosa, 102 specimens of paired
      metastatic lymph nodes, 30 specimens of dysplasia, 30 specimens of intestinal
      metaplasia, 10 specimens of chronic superficial gastritis, and 5 specimens of
      normal gastric mucosa, and the expression of P27 and PTEN in 138 specimens of
      gastric cancer were detected by immunohistochemistry. RESULTS: Skp2 labeling
      frequency was significantly higher in intestinal metaplasia [(12.68+/-0.86)%] and
      adjacent mucosa [(19.32+/-1.22)%] than in chronic superficial gastritis [(0.53+/
      0.13)%] and normal gastric mucosa [(0.47+/-0.19)%] (P<0.001), but there was no
      difference between chronic superficial gastritis and normal gastric mucosa
      (P>0.05); Skp2 labeling frequency was significantly higher in dysplasia [(16.74+/
      0.82)%] than in intestinal metaplasia (P<0.001), significantly higher in primary
      gastric carcinoma [(31.34+/-2.17)%] than in dysplasia and adjacent mucosa
      (P<0.001), and significantly higher in metastatic lymph node [(39.76+/-2.00)%]
      than in primary gastric carcinoma (P=0.037). Skp2 labeling frequency in gastric
      carcinoma was positively correlated with differentiation grade (rs=0.315,
      P<0.001), vessel invasion (rs=0.303, P<0.001), and lymph node metastasis
      (rs=0.254, P=0.001). Skp2 expression was negatively correlated with both P27
      expression (rs=-0.451, P<0.001) and PTEN expression (rs=-0.480, P<0.001) in
      gastric carcinoma. P27 expression was positively correlated with PTEN expression
      in gastric carcinoma (rs=0.642, P<0.001). CONCLUSION: Skp2 overexpression, which
      may lead to degradation of P27 and low expression of PTEN, may be a very
      important reason in carcinogenesis and progression of gastric carcinoma.

PMID- 16405749
TI  - [Effect of exogenous RGS16 gene transfection on growth of glioma cell line C6].
AB  - BACKGROUND & OBJECTIVE: Wild type p53 could induce RGS16 mRNA expression, and
      RGS16 protein is related with carcinogenesis of glioma. This study was designed
      to investigate the effects of exogenous RGS16 gene transfection on the growth of
      rat glioma cell line C6. METHODS: A eukaryotic expression plasmid pIRES2-EGFP
      RGS16 was constructed, and transfected into C6 cells. The cells were selected by
      G418. The expression of enhanced green fluorescent protein (EGFP) was observed
      under fluorescent microscope, and the expression of RGS16 mRNA and protein was
      detected by reverse transcription-polymerase chain reaction (RT-PCR) and
      immunocytochemistry. The effects of RGS16 gene on cell cycle progression, cell
      growth, and proliferation of C6 cells were measured by flow cytometry, cell
      growth curve, and clonogenic assay in plate. RESULTS: C6-RGS16 and C6-GFP cells,
      which separately expressed RGS16 and pIRES2-EGFP vector, were constructed
      successfully. S phase proportion was significantly higher in C6-RGS16 cells than
      in C6-GFP and C6 cells (28.5% vs. 18.9% and 14.3%, P<0.05); C6-RGS16 cells grew
      faster than C6-GFP and C6 cells. The clone formation rate was significantly lower
      in C6-RGS16 cells than in C6-GFP and C6 cells (12% vs. 25% and 25%, P<0.05).
      CONCLUSION: Exogenous RGS16 gene could promote cell cycle progression of glioma
      C6 cells from G1 phase to S phase, and accelerate cell growth, but can't increase
      the clone formation.

PMID- 16405751
TI  - [Factors influencing clinical target volume delineation of intact breast in
      intensity-modulated radiotherapy for breast cancer].
AB  - BACKGROUND & OBJECTIVE: In patients with breast cancer who underwent breast
      conservation treatment, intensity-modulated radiotherapy (IMRT) has been approved
      to hold better dosimetric advantages and improbable future. Target delineation is
      the most important process, which determines the accuracy of planning and
      application of IMRT. However, there is no consensus criterion for the delineation
      of clinical target volume (CTV) of intact breast. This study was to investigate
      the factors influencing the delineation of CTV of intact breast in IMRT for
      breast cancer. METHODS: The CTV of intact breast in 6 patients was delineated by
      4 radiation oncologists and 1 radiologist individually, and reference CTV was
      determined by group consensus. The extent of variation in CTV delineation was
      quantified by the ratio of common volumes (Vco) of all CTVs to the maximum volume
      encompassing all CTVs (Vmax). The deviation in the extent of CTV from the extent
      of reference CTV was quantified in each orthogonal direction to find the origins
      of variations. In addition, all central lung distances (CLD) in tangential
      fields, which were designed based on CTVs, were measured. RESULTS: The ratios of
      Vco to Vmax were low (0.660 and 0.651, respectively) in 2 patients with low
      glandular density. Among the other 4 patients with high glandular density, the
      ratio was relatively higher in 2 patients with radio-opaque marks than in the
      other 2 patients with no marks (0.799, 0.769 vs. 0.735, 0.752, respectively).
      Compared with reference CTVs, the patients' average deviations of the extent of
      CTVs were 0 in anterior direction, (1.2+/-3.4) mm in posterior direction, (1.5+/
      2.1) mm in cranial direction, (0.7+/-4.1) mm in caudal direction, (0.6+/-3.3) mm
      in medial direction, and (0.8+/-0.8) mm in lateral direction. The most obvious
      variations were observed in the area of breast axillary part and primary tumor
      bed after surgery. The mean CLD in 4 patients exceeded over the conventional
      limitation of 2 cm. CONCLUSION: The variability between CTVs of intact breast
      delineated by different radiation oncologists is strongly related to individual
      glandular density, the extent of breast axillary part, the primary tumor bed
      after surgery, and the different understanding for lung sparing limitations.

PMID- 16405752
TI  - [Comparing serum tumor antigen detection combined with CT scan with PET-CT for
      lung cancer diagnosis].
AB  - BACKGROUND & OBJECTIVE: Positron emission tomography-computed tomography (PET-CT)
      is a new bio-imaging system which combined metabolic with anatomic imaging. This
      system has better three-dimensional definition and earlier tumor detection
      potential. This study was to compare the accuracy of tumor antigen detection
      combined with CT scan with PET-CT for lung cancer diagnosis and staging. METHODS:
      A total of 43 lung cancer patients diagnosed by operation or acupuncture,
      received breast CT scan, tumor antigen detection, and PET-CT scan, were selected.
      The accuracies of these 2 methods and their impacts on lung cancer staging were
      compared. RESULTS: The accurate diagnosis rate of tumor antigen detection
      combined with CT scan was 67.44%, and that of PET-CT scan was 90.70%. Local focus
      detection rates were 86.05% and 95.35%, respectively; mediastinal lymph nodes
      detection rates were 65.12% and 83.72%, respectively. PET-CT detected 6 cases of
      distant metastasis which were not detected by tumor antigen detection combined
      with CT scan. Compared with CT scan, 5 (11.63%) cases were upstaged and 7
      (16.28%) cases were downstaged by PET-CT, which led to therapeutic strategy
      changes in 4 (9.3%) cases. CONCLUSION: Compare with tumor antigen detection
      combined with CT scan, PET-CT scan is more sensitive and accurate in diagnosing
      and staging lung cancer.

PMID- 16405753
TI  - [Expression of AKT2, cyclin D1, and MMP-9 and their correlations to
      clinicopathologic features of non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: AKT2, a serine/threonine kinase, is confirmed to be an
      oncogene. Abnormal expression and activation of AKT2 is observed in many kinds of
      tumor tissues. AKT2 is associated with the proliferation and invasion of cancers.
      This study was designed to investigate the expression of AKT2, Cyclin D1, and
      matrix metalloproteinase-9 (MMP-9) in human non-small cell lung cancer (NSCLC)
      tissue and their correlations to clinicopathologic features of NSCLC. METHODS:
      The expression of AKT2, Cyclin D1, and MMP-9 in 68 specimens of NSCLC, 38
      specimens of corresponding adjacent tissues, and 14 specimens of no-cancerous
      lung tissue were assessed by immunohistochemistry; their correlations to
      clinicopathologic factors were analyzed using Chi-square test. RESULTS: The
      positive rates of AKT2, Cyclin D1, and MMP-9 were significantly higher in NSCLC
      than in adjacent tissues and no-cancerous lung tissues (91.2% vs. 3.8%, 76.5% vs.
      0%, 72.1% vs. 13.5%, P<0.05). The expression of AKT2 wasn't correlated to age,
      sex, histologic subtype and differentiation, and TNM stage of NSCLC patients
      (P>0.05), but was correlated to lymph node metastasis (P<0.05). The expression of
      Cyclin D1 and MMP-9 was correlated to lymph node metastasis and differentiation
      of squamous cell carcinoma (P<0.05); the expression of MMP-9 was correlated to
      TNM stage. The expression of AKT2 was positively correlated to the expression of
      Cyclin D1 and MMP-9 (P<0.05). CONCLUSIONS: AKT2, Cyclin D1, and MMP-9 is related
      to development of lung cancer. The overexpression of Cyclin D1 and MMP-9 may
      relate to AKT2 regulation.

PMID- 16405754
TI  - [Surgical treatment for 217 patients with bladder transitional carcinoma].
AB  - BACKGROUND & OBJECTIVE: Bladder transitional cell carcinoma (TCC) is the most
      common cancer among urogenital neoplasms. Surgical operation is the most
      effective therapy for TCC. This study was to explore surgical treatment for TCC
      and its clinical significance. METHODS: Clinical data, including disease-free
      survival, recurrence and death, of 217 TCC patients who had received different
      surgical procedures were retrospectively analyzed. RESULT: After a median follow
      up of 30 months, 195 patients were free of disease, recurrence was observed for
      56 times. Fourteen patients died: 13 of them died of progressive disease, and 1
      died of renal failure. None death occurred in patients with stage T1 or grade I
      tumor. The overall 2-year survival rate was 89.6%. The survival rate and disease
      freely survival rate were negatively correlated to stage and grade of the tumors.
      The prognosis of stage T1 and T4 patients had no correlation to surgical
      procedures. For stage T2 and T3 tumors, the prognosis of the patients who
      received radical cystectomy was significantly better than that of the patients
      who received organ sparing procedure. CONCLUSIONS: The organ sparing treatment is
      safe for patients with early stage and well differentiated TCC. Radical
      cystectomy should be done in time for patients with advanced and poorly
      differentiated TCC.

PMID- 16405755
TI  - [Nephron-sparing surgery for localized kidney neoplasms--a report of 25 cases].
AB  - BACKGROUND & OBJECTIVE: Nephron-sparing surgery (NSS) was initially used in
      treating bilateral renal cell carcinoma (RCC) or RCC in a solitary functioning
      kidney with good effectiveness. The satisfied long-term outcome was also obtained
      in patients with unilateral localized RCC and a normal contralateral kidney after
      NSS. This paper was to report our experiences in treating localized renal tumor
      with NSS. METHODS: From Nov. 1999 to Dec. 2004, 25 patients were diagnosed with
      localized RCC preoperatively, and treated with NSS. During operation, renal
      circulation was temporarily interrupted in 8 patients, surface cooling of the
      kidney with ice slush was performed in 3 patients, frozen section pathology was
      performed in 16 patients. RESULTS: The operation was technically successful in
      all cases. The median operating time was 129 min (ranged 65-205 min). The mean
      blood loss was 310 ml (ranged 100-800 ml) with 1 case of blood transfusion.
      Except for 1 case of urinary fistula which was cured conservatively, there was no
      other postoperative complication. Intraoperative pathology confirmed that the
      surgical margin of all cases were negative. Of the 25 cases, 19 were renal clear
      cell carcinoma, 2 were renal granular cell carcinoma, 4 were hamartoma. The
      pathologic stage was pT1N0M0 in 21 patients. The mean follow-up time was 22
      months (ranged 6-55 months). No local tumor recurred, and all patients survived
      disease-freely. CONCLUSIONS: NSS is effective in treating localized RCC. We
      recommend NSS to patients with unilateral localized, but not center, kidney tumor
      less than 4 cm and a normal contralateral kidney.

PMID- 16405757
TI  - [Treatment and prognosis of stage T3 glottic laryngeal cancer--a report of 65
      cases].
AB  - BACKGROUND & OBJECTIVE: Clinical treatment of stage T3 glottic laryngeal cancer
      still remains controversial. This study was to explore the influences of
      different treatment modalities, lymph node metastasis, and positive margin on
      prognosis of stage T3 glottic cancer. METHODS: Records of 65 stage T3 glottic
      cancer patients, treated in Cancer Center of Sun Yat-sen University from Jan. 1,
      1990 to Dec. 30, 1998, were retrospectively analyzed. The influences of different
      treatments, lymph node metastasis, and positive margin on survival of the
      patients were analyzed. RESULTS: The 3- and 5-year overall survival rates were
      75.47% and 65.07%. No significant difference was found among surgery alone,
      radiotherapy alone, and surgery plus adjuvant radiotherapy groups (P=0.914),
      between partial laryngectomy and total laryngectomy groups (P=0.710), and between
      positive margin and negative margin groups (P=0.176). The lymph node metastasis
      rate was 18.5%, and the occult lymph node metastasis rate was 10.8%. Lymph node
      metastasis was a poor prognostic factor (P<0.001). CONCLUSIONS: The influences of
      different treatments on survival of stage T3 glottic cancer patients are similar,
      and the effects of partial laryngectomy and total laryngectomy are also similar.
      Lymph node metastasis affects prognosis, and wait-and-see is recommended to cN0
      patients. The survival of patients with positive margin after postoperative
      radiotherapy is similar to that of patients with negative margin.

PMID- 16405756
TI  - [Treatment and prognosis of stage III-IV laryngeal squamous cell carcinoma].
AB  - BACKGROUND & OBJECTIVE: Laryngeal squamous cell carcinoma (LSCC) is a common
      malignancy of the head and neck. Stage I-II LSCC patients have a favorable
      prognosis after operation or radiotherapy, but the curative effect and prognosis
      of stage III-IV LSCC are not satisfying, and its treatment is also controversial.
      This study was to summarize our experience in treating stage III-IV LSCC
      patients, evaluate the treatment results, and seek more reasonable therapeutic
      modality. METHODS: Records of 202 stage III-IV LSCC patients, treated in Cancer
      Center of Sun Yat-sen University from Jan. 1, 1991 to Jan. 1, 2000, were
      retrospectively analyzed. Of the 202 patients, 64 received surgery alone, 83
      received surgery and preoperative or postoperative radiotherapy, 41 received
      radiotherapy, and 14 received chemotherapy. The overall survival rate was
      estimated using life table method by SPSS10.0 software. Survival curves were
      compared with Wilcoxon method; relapse statuses were compared with Chi(2) test.
      RESULTS: The 5- and 10-year overall survival rates of the 202 patients was
      (42.12+/-3.62)% and (33.20+/-4.32)%, and the median survival time was 48.5
      months. The 5-year survival rates were 61.07% in glottic carcinoma group and
      26.07% in supraglottic carcinoma group, and were 53.41% in surgery alone group,
      51.04% in surgery plus radiotherapy group, 18.33% in radiotherapy group and 7.14%
      in chemotherapy group. There was no significant difference between surgery alone
      group and surgery plus radiotherapy group (P>0.05). Of the 147 patients received
      surgery, the 5-year survival rates were 56.15% for the 31 patients received
      partial laryngectomy and 52.08% for the 116 patients received total laryngectomy.
      Eleven patients had tumor relapsed after total laryngectomy within 5 years.
      CONCLUSIONS: Surgery, especially total laryngectomy, is the major treatment
      modality for stage III-IV LSCC. Partial laryngectomy may be performed with strict
      selection. Postoperative radiotherapy may be preformed on the patients with
      suspect of tumor residue or positive margin.

PMID- 16405758
TI  - [Clinical features and diagnosis of langerhans cell hyperplasia].
AB  - BACKGROUND & OBJECTIVE: The incidence rate of langerhans cell hyperplasia (LCH)
      is increasing. Its clinical manifestation is so diversified that it is easy to be
      misdiagnosed. This study was to analyze its clinical features for the sake of
      early diagnosis and treatment. METHODS: Clinical data of 44 LCH patients, treated
      from Jan. 1990 to Dec. 2003 in the First Affiliated Hospital of Sun Yat-sen
      University, were retrospectively analyzed. RESULTS: Of the 44 LCH patients, 32
      (72.7%) were children, 12 (27.3%) were adults. Of the 32 children patients, 15
      (46.9%) were less than 2 years old. The involved organs were bone (20/44, 45.5%),
      lymph nodes (20/44, 45.5%), skin (16/44, 36.4%), liver and spleen (16/44, 36.4%),
      lung (14/44, 31.8%), bone marrow (6/44, 13.6%), ear (4/44, 9.1%), eyes (2/44,
      4.5%), pituitary gland (2/44, 4.5%), and thymus gland (1/44, 2.3%). Of the 44
      patients, 10 had 1 organ involved, 11 had 2 organs involved, 9 had 3 organs
      involved, 7 had 4 organs involved, 7 had no less than 5 organs involved; 22
      children patients and 4 adult patients had multiple organs (liver, lung, bone
      marrow, and so on) involved; 26 (59.1%) were misdiagnosed as dermatosis (6
      cases), hemopathy (7 cases), bone or bone marrow diseases (7 cases), lung
      tuberculosis (2 cases), diabetes insipidus (2 cases), ear or eye disease (2
      cases). Six children patients had bronchopneumonia, and 4 of them had septicemia.
      Six patients died with 5 cases below the age of 2. CONCLUSIONS: LCH is easy to be
      misdiagnosed. Children below 2 years old tend to complicate with multiple organ
      failure (MOF) and bronchopneumonia which have high death rate. Pathology
      examination is helpful for early diagnosis, treatment, and prevention of severe
      complications.

PMID- 16405760
TI  - [Recurrence patterns of esophageal cancer after Ivor-Lewis esophagectomy--a
      report of 196 cases].
AB  - BACKGROUND & OBJECTIVE: About one half of the patients with esophageal cancer may
      recur within 3 years after operation, but the recurrence pattern is still
      unclear. This study was to investigate the recurrence patterns of esophageal
      cancer after Ivor-Lewis esophagectomy. METHODS: Clinical data of 196 patients
      with squamous cell carcinoma of the middle third thoracic esophagus, who
      underwent Ivor-Lewis esophagectomy with two-field lymph node dissection from Jan.
      1997 through Jan. 2001, were reviewed. The risk factors of postoperative
      recurrence within 3 years were analyzed with Logistic regressive model. RESULTS:
      Recurrence was recognized in 96 (48.9%) patients within 3 year after operation.
      The median time to recurrence was 12.2 months. Of the 96 cases of recurrence, 52
      (54.1%) were locoregional, including 41 cases (78.8%) of mediastinal lymph node
      metastasis, and 8 cases (15.3%) of single cervical lymph node metastasis; 44
      (45.8%) were hematogenous, including 10 cases of locoregional-hematogenous
      recurrence, and mainly located at liver, bone, and lung (39, 88.6%). The
      locoregional recurrence rate was significantly lower in the patients who received
      postoperative radiotherapy than in the patients have not received postoperative
      radiotherapy (23.3% vs. 41.3%, P<0.05). Logistic analysis showed that T3 and N1
      tumor were independent risk factors of postoperative tumor recurrence.
      CONCLUSIONS: About one half of the patients would develop recurrent disease
      within 3 years after Ivor-Lewis esophagectomy, and most of them were with
      mediastinal lymph node, liver, bone, or lung metastasis. Postoperative
      radiotherapy is helpful to control locoregional recurrence.

PMID- 16405759
TI  - [Expression and significance of C-kit and platelet-derived growth factor receptor
      beta (PDGFRbeta) in esophageal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Some researches have showed that STI-571 could inhibit
      tyrosine kinase of Bcr-Abl, C-kit, and platelet-derived growth factor receptor
      beta (PDGFRbeta), therefore, inhibit cell differentiation and proliferation and
      accelerate cell apoptosis. This study was to examine the expression of tyrosine
      kinase receptor C-kit and PDGFRbeta, which is correlated to STI-571, in
      esophageal carcinoma. METHODS: The expression of C-kit and PDGFRbeta in tumor
      tissue, para-tumor tissue, and normal tissue of 50 specimens of esophageal
      carcinoma was examined by immunohistochemistry. RESULTS: The strong expression
      rate of C-kit was low in tumor, para-tumor, and normal tissues (4%, 4%, and 12%,
      respectively), with no significant difference (P=0.220). The strong expression
      rate of PDGFRbeta was significantly higher in tumor tissues than in para-tumor
      and normal tissues (68% vs. 28% and 28%, P=0.001). Logistic regression analysis
      revealed that the strong expression rate of C-kit and PDGFRbeta had no
      correlation to sex, age, differentiation degree, infiltrative depth, position,
      lymph node metastasis, and stage of esophageal carcinoma. CONCLUSIONS: The strong
      expression rate of PDGFRbeta is significantly higher in tumor tissues than in
      para-tumor and normal tissues. The strong expression rate of C-kit in normal
      esophageal tissues is low, and it is lower in para-tumor and tumor tissues.

PMID- 16405761
TI  - [Clinical analysis of 123 gastric cardia carcinoma patients treated with surgical
      operation].
AB  - BACKGROUND & OBJECTIVE: The prevalence of gastric cardia carcinoma is increasing
      in recent decades, necessitating further research on it. However, there are still
      debates on its clinical management. This study was to summarize our experiences
      in surgical treatment of gastric cardia carcinoma. METHODS: A total of 123
      gastric cardia carcinoma patients, received surgical operation, were divided into
      3 groups according to surgical approaches: 72 in thoracic group, 40 in abdominal
      group, and 11 in thoracoabdominal group. Clinical data, including preoperative
      examination, surgical approach, lymph node dissection, and postoperative
      pathology, of the patients were analyzed. RESULTS: Setting pathologic results as
      golden standard, the correct diagnosis rates of preoperative ultrasound for
      serosal involvement, lymph node metastasis, distal esophageal involvement, and
      others (including liver metastases, extended invasion, and ascites) were 71.2%,
      62.2%, 47.8%, and 100%, respectively; those of CT were 78.6%, 72.7%, 51.9%, and
      100%, respectively. Endoscopy could indicate the distance between tumor and
      incisor, and barium meal showed the relationship between tumor and diaphragm. The
      curative resection rate was 94.3% (116/123); among the 116 cases, 108 (93.1%)
      were adenocarcinoma, 2 were squamous cell carcinoma, 2 were adenosquamous
      carcinoma, 2 were atypical carcinoid, and 2 were carcinoid; 84 (72.4%) had
      abdominal lymph node metastases, 6 (7.1%) had thoracic lymph node metastases, and
      40 (34.5%) had distal esophageal involvement. CONCLUSIONS: Preoperative abdominal
      ultrasound and thoracoabdominal CT scan are helpful in evaluating respectability
      of gastric cardia carcinoma. Endoscopy and barium meal may be helpful in deciding
      the surgical approach. Abdominal lymph node is the main route of lymphatic
      dissemination of gastric cardia carcinoma. The efficacies of the 3 surgical
      approaches are similar; each has its benefit. Surgical modalities should be
      carried out individually according to Siewert classification and patient's
      conditions.

PMID- 16405762
TI  - [Significance of dynamic enhanced MRI in differential diagnosis of radiofibrosis
      and recurrent nasopharyngeal carcinoma at the basilar clivus].
AB  - BACKGROUND & OBJECTIVE: Basilar clivus is a common site of recurrent
      nasopharyngeal carcinoma (RNPC). Biopsy of the basilar clivus is seldom done
      because of its deep location and complex anatomic structure, therefore, early
      differential diagnosis of radiofibrosis (RF) and RNPC at the basilar clivus is
      very difficult. This study was designed to investigate the characteristics of
      radiofibrosis and RNPC at the basilar clivus on dynamic enhanced magnetic
      resonance imaging (DMRI) for differential diagnosis. METHODS: A total of 38 NPC
      patients, treated in Cancer Center and the Second Affiliated Hospital of Sun Yat
      sen University with follow-up of 1-5 years, were divided into 2 groups: 22 in RF
      group and 16 in RNPC (RNPC at the basilar clivus) group. After conventional plain
      MRI scan of nasopharynx, DMRI and conventional contrast enhanced T(1)-weighted
      imaging (T1WI) were performed. Maximal contrast enhancement ratio (MCER), time to
      MCER (Tmax), and contrast enhancement ratio at the 40th second of DMRI (CER(40s))
      of basilar clivus, condylar process, and nasal concha were measured. RESULTS: The
      MCER and CER(40s) of RF at the basilar clivus were lower, and the Tmax was longer
      than those of RNPC at the basilar clivus. When CER40s > or =150%, CER40s of
      basilar clivus > or = CER(40s) of nasal concha, and the combination of these 2
      indexes were respectively set as the DMRI diagnostic criteria of RNPC at the
      basilar clivus, the diagnostic sensitivity of the second criterion was the
      highest (81.3%), and the diagnostic specificity of the third criterion was also
      the highest (86.4%). CONCLUSIONS: DMRI is helpful for differential diagnosis of
      radiofibrosis and RNPC at the basilar clivus. RNPC at the basilar clivus is
      highly suggested when it meet the criteria of both CER(40s) > or =150% and
      CER(40s) of basilar clivus > or = CER(40s) of nasal concha. When the 2 criteria
      are conflictive, the latter is more accurate, MCER and Tmax of the basilar clivus
      should be took into consideration.

PMID- 16405763
TI  - [Calibration of CT values used for radiation treatment planning and its impact
      factors].
AB  - BACKGROUND & OBJECTIVE: CT values are the basis that radiation treatment planning
      system (TPS) used to calculate the dose distribution of an irradiation treatment
      plan. However, the CT values of a certain tissue could be very different when it
      is scanned with dissimilar parameters or acquisition modes, and would add errors
      to the planning dose calculation. This study was designed to investigate the
      factors that may impact the calibration of quantitative CT used for radiation
      treatment planning, and determine the relative importance of these factors.
      METHODS: CT values of different tissue substitute rods under different CT
      scanning conditions were measured and compared using RMI 467 phantom. Scanning
      conditions were classified into 3 modes: (1) evaluating the effect of CT
      parameters on CT density map by choosing different voltage, slice thickness and
      acquisition modalities; (2) evaluating the geometric effects of patient size,
      shape and position in the field of view (FOV) by changing different position of
      tissue substitute rods in the phantom; (3) evaluating the effect of patient
      support table on quantitative CT by comparing CT values acquired on patient
      support table top with those acquired in air. The relative importance leading to
      CT value error of the 3 modes was also analyzed. RESULTS: For high-density
      cortical bone, the applied voltage was the most relevant factor resulting in
      difference to the reconstructed Hounsfield values of about 150 units, which was
      12.7% when scanning voltage changed from 120 KV to 150 KV. The geometric
      disturbance from different patient sizes and shapes in the FOV could be minimized
      (less than 10 units for cortical bone). The CT values acquired on the table top
      varied about 26.34% for water and 293.84% for solid water when compared with
      those acquired in air. CONCLUSIONS: CT scan voltage and patient support table top
      scattering make the most impacts to CT values, which may result in error of TPS
      dose calculation. Inhomogeneous phantoms like RMI 467 can be used to perform QA
      tests, and calibrations for quantitative CT and reduce the dose error of
      radiation treatment. It is advisable that a complete set of CT parameters and
      image acquisition modalities should be determined as part of radiotherapy
      planning protocols. Patient setup and immobilization modality during CT
      acquisition should be the same as those during treatment delivery, so as to
      increase the accuracy of the CT density map for TPS.

PMID- 16405764
TI  - [Measurement of setup error in conformal radiotherapy for nasopharyngeal
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Setup error is the key factor in determining the margin
      of planning target volume (M(PTV)) for conformal radiotherapy of nasopharyngeal
      carcinoma (NPC). This study was to establish a method using radiopaque fiducial
      markers which were embedded in occlusal splint ("occlusal splint method") to
      acquire setup errors to calculate M(PTV) in CRT for NPC. METHODS: The occlusal
      splint method was performed in 22 NPC patients who received CRT. Setup errors
      were calculated by comparing the coordinates of 3 fiducial markers read from
      portal images with those read from computed tomography (CT) data. According to
      the formulation, the size of MPTV with or without consideration of organ motion
      was also calculated. RESULTS: The standard deviations of systematic errors
      (Sigma) were 1.13 mm, 1.47 mm, and 1.31 mm in X (medio-lateral), Y (antero
      posterior) and Z (cranio-caudal) axes, respectively; the standard deviations of
      random errors were 0.81 mm, 0.45 mm, and 0.80 mm in X, Y, and Z axes,
      respectively. Without consideration of organ motion, the sizes of M(PTV) were
      3.40 mm, 3.98 mm, and 3.83 mm in X, Y, and Z axes, respectively; with
      consideration of organ motion, the sizes of M(PTV) were 3.75 mm, 4.35 mm, and
      4.16 mm in X, Y, and Z axes, respectively. CONCLUSION: Using the "occlusal splint
      method", each institution can precisely calculate setup error data, and stipulate
      the size of M(PTV) adequate to one's own situation.

PMID- 16405765
TI  - [A bi-isocentric irradiation technique in radiotherapy for nasopharyngeal
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Although the problem of fields gap in radiotherapy for
      nasopharyngeal carcinoma (NPC) was solved by mono-isocentric technique, the dose
      distribution was heterogeneous with "hot" and/or "cold" spots. This study was to
      explore the best way to solve the problems of both fields gap and dose
      distribution using bi-isocentric technique. METHODS: Mono-isocentric and bi
      isocentric irradiation techniques were used to simulate irradiation,
      respectively. Mono-isocentric irradiation technique was used to design the beam
      split facio-upper neck field and the tangential low neck-supraclavicular field at
      the match plane. Bi-isocentric irradiation technique was used to design the facio
      upper neck field and the tangential low neck-supraclavicular field at the match
      plane, namely the upper border of the tangential field and the lower border of
      the facio-upper neck fields. RESULTS: Both mono-isocentric and bi-isocentric
      irradiation techniques were conformed well to QA at the junction of the
      neighboring portals, without "hot" or "cold" spots, by dosimetry. But the CADplan
      Three Dimensions Treatment Planning System showed that the dose distributional
      uniformity of sagittal plane in nasopharynx was much better in bi-isocentric
      technique than in mono-isocentric irradiation technique, without cold region in
      gross tumor volume (GTV) and/or hot region in normal tissue. CONCLUSIONS: Bi
      isocentric irradiation technique takes a perfect match-plane and a satisfied dose
      distributional uniformity.

PMID- 16405766
TI  - [Application of molecular imaging to chemotherapy].
AB  - Molecular imaging is a new subject of exploring the biological metabolism process
      of the cells or organs in living organisms with some non-invasive technologies,
      such as PETE-CT, MR, and optical imaging instruments, using specific molecular
      probes to investigate the pathologic and physiologic metabolisms of the patients
      at molecular and gene levels. With the development of this technology, molecular
      imaging plays a more and more important role in guiding cancer chemotherapy,
      choosing sensitive medicines, planning treatment scheme, evaluating chemotherapy
      effect, and so on.

PMID- 16405768
TI  - [Effects of chronic mercury poisoning on blood coagulation and fibrinolysis
      systems].
AB  - OBJECTIVE: To investigate the effects of chronic mercury poisoning on blood
      coagulation and fibrinolysis systems, and the possible mechanism. METHODS: Twenty
      seven patients with chronic mercury poisoning were studied with 30 healthy people
      as control. Thrombomodulin (TM), tissue plasminogen activator (t-PA), plasminogen
      activator inhibitor (PAI), interleukin-13 (IL-13), interleukin-18 (IL-18),
      soluble intercellular adhesion molecule-1 (SICAM-1) were examined with ELISA
      methods, and superoxide dismutase (SOD) and lipid peroxidation (LPO) was examined
      with chemical catalysis methods. Two to three weeks after treatment with reduced
      glutathione, tiopronin and daidzein, blood was used for determin the above items
      again. RESULTS: (1) The concentration of TM in patients [(2.36 +/- 0.16) ng/ml]
      was significantly lower than in the control [(4.36 +/- 0.24) ng/ml] (P < 0.01),
      while TM tended to be higher after treatment [(4.82 +/- 0.34) ng/ml] (P < 0.05).
      (2) The concentration of t-PA in patients [(3.44 +/- 0.34) ng/ml] was
      significantly lower than in the control [(4.52 +/- 0.16) ng/ml] (P < 0.05), and
      was higher significantly [(5.63 +/- 0.58) ng/ml] after treatment (P < 0.05); The
      concentration of PAI in patients [(48.23 +/- 3.59) ng/ml] was significantly
      higher than in the control [(31.59 +/- 2.13) ng/ml] (P < 0.05), but after
      treatment no significant change [(50.71 +/- 4.29) ng/ml] was found (P > 0.05).
      (3) The activity of SOD in patients [(953.85 +/- 9.56) U/g Hb] was significantly
      lower than in the control [(1,308.75 +/- 10.21) U/g Hb] (P < 0.01), and was
      higher significantly [(1,217.95 +/- 6.29) U/g Hb] after treatment (P < 0.05); and
      the concentration of LPO in patients [(9.53 +/- 0.26) nmol/ml] was significantly
      higher than in the control (P < 0.05), and significantly lower [(7.29 +/- 0.35)
      nmol/ml] after treatment (P < 0.05). (4) The concentrations of IL-13 [(35.93 +/-
      5.28) pg/ml], IL-18 [(28.79 +/- 2.53) pg/ml], SICAM-1 [(603.16 +/- 29.12) ng/ml]
      were significantly higher than those in the controls (P < 0.05, P < 0.01), but no
      significant difference was found after treatment. CONCLUSION: Dysfunction of the
      TM/protein C system and t-PA/PAI system (i.e. the decrease of anti-coagulation
      activity and the inhibition of the function for the fibrolysis system) may play a
      key role in the secondary hypercoagulable state induced by chronic mercury
      poisoning.

PMID- 16405767
TI  - [Isometric muscle strength measurements and assessment: a pilot study].
AB  - OBJECTIVE: To determine the anthropometric parameters and the isometric muscle
      strength in a working population sample in China, and to investigate the
      relationship between muscle strength and individual attributes, such as age,
      gender, height and weight. METHODS: The study population consisted of 146 male
      and 47 female people including workers, administrators and college students. Four
      types of muscle strength, i.e., handgrip, arm lift, shoulder lift, and torso
      pull, were measured. RESULTS: Left handgrip, right handgrip, arm lift, shoulder
      lift and torso pull of male workers were (42.07 +/- 7.20), (43.92 +/- 7.14),
      (26.79 +/- 4.64), (33.79 +/- 6.88), (88.56 +/- 17.98) kg, respectively while
      those of female workers were (21.29 +/- 5.09), (23.26 +/- 5.47), (13.29 +/-
      3.37), (18.52 +/- 4.01), (41.06 +/- 12.04) kg, respectively. The female's
      strength was about 50% lower than the male's. The strength in the 40
      approximately years old group was higher than that in other age groups. There
      were significant positive correlation between the gender and the isometric
      strength as well as between the body weight and the isometric strength. If the
      body weight served as the corrected parameter, there was no significant
      difference in the handgrip among the groups (P < 0.05), but the torso pull of
      male workers > college students > administrators. All relative muscle strengths
      except the torso pull were similar for all age groups. CONCLUSION: The body
      weight as the independent variable can be used for establishing the predictive
      equation of the muscle strength. Calculation of the relative muscle strength can
      relieve the interference of the body weight for the muscle strength.

PMID- 16405769
TI  - [Preventive effects of vitamin E on short-term noise-induced hearing loss in
      guinea pigs].
AB  - OBJECTIVE: To study the preventive effects of vitamin E on short-term noise
      induced hearing loss (NIHL). METHODS: Forty-eight male pigmented guinea pigs were
      randomly divided into 6 groups, 8 animals in each group. The animals of group 1,
      2, 3, 4 were exposed to the noise (4 kHz octave band noise, 100 dB SPL), 8 hours
      per day for 3 days consecutively and received normal saline, corn oil, 10 mg/kg
      vitamin E, 50 mg/kg vitamin E respectively daily by intraperitoneal injection
      from 3 days before the noise exposure, through the 3 noise exposure days to 3
      days after the noise exposure. The animals of group 5 and group 6 days were not
      exposed to the noise but received normal saline and 50 mg/kg vitamin E injection
      respectively at the same time as that of group 1, 2, 3, 4. The preventive effects
      of vitamin E on NIHL were determined by comparing the threshold shifts of
      auditory brainstem responses (ABR) immediately, on the second day and on the 8th
      day after the exposure. RESULTS: The ABR threshold shifts immediately, on the
      second day and on the 8th day after the exposure for group 3 at 2, 4 and 8 kHz
      were (15.9 +/- 6.8), (39.4 +/- 4.8), (42.5 +/- 6.3), (0.3 +/- 2.5), (19.1 +/-
      7.9), (21.9 +/- 6.4), (0.3 +/- 1.6), (10.9 +/- 8.6), (12.2 +/- 8.1) dB,
      respectively, which were significantly lower than those for group 1 [(30.9 +/-
      11.3), (47.8 +/- 8.8), (49.7 +/- 6.9), (10.0 +/- 3.5), (29.1 +/- 6.5), (29.1 +/-
      7.6), (4.7 +/- 3.6), (20.3 +/- 6.5), (17.5 +/- 9.0) dB, respectively] (P < 0.05).
      The ABR threshold shifts immediately, on the second day and on the 8th day after
      the exposure for group 4 at 2, 4 and 8 kHz were respectively (14.4 +/- 5.3),
      (36.6 +/- 4.4), (43.1 +/- 2.9), (0.3 +/- 2.5), (16.9 +/- 4.6), (19.4 +/- 3.2),
      (0.0 +/- 3.7), (7.5 +/- 4.2), (9.1 +/- 4.2) dB, which were significantly lower
      than those for group 1 (P < 0.05). CONCLUSION: Vitamin E has some preventive
      effects on the NIHL.

PMID- 16405770
TI  - [Investigating genetic damage of workers occupationally exposed to methotrexate].
AB  - OBJECTIVE: To study genetic damage of workers alone occupationally exposed to
      methotrexate (MTX) with three end-points. METHODS: The blood samples from 21
      workers exposed to MTX and 21 controls were detected with micronucleus test,
      comet assay, hprt gene mutation test and TCR gene mutation test. RESULTS: The
      mean micronuclei rate (MNR) and mean micronucleated cells rate (MCR) in 21
      workers were 10.10 per thousand +/- 0.95 per thousand and 8.05 per thousand +/-
      0.75 per thousand, respectively, which were significantly higher than those (5.48
      per thousand +/- 0.82 per thousand and 4.38 per thousand +/- 0.58 per thousand)
      in control (P < 0.01). The mean tail length (MTL) of 21 workers and 21 controls
      were (1.30 +/- 0.06) microm and (0.07 +/- 0.01) microm, respectively, there was
      significant difference between workers and controls (P < 0.01). But the
      difference between workers and controls for mean tail moment (MTM) was not
      significant (P > 0.05). The average mutation frequency (Mf-hprt) of hprt and (Mf
      TCR) of TCR in workers were 1.00 per thousand +/- 0.02 per thousand and (6.87 +/-
      0.52) x 10(-4), respectively, which were significantly higher than those [0.86
      per thousand +/- 0.01 per thousand and (1.67 +/- 0.14) x 10(-4)] in control (P <
      0.01). CONCLUSION: The genetic damage to some extent appeared in workers
      occupationally exposed to methotrexate.

PMID- 16405771
TI  - [Effects of extremely low frequency electromagnetic fields on DNA of testicular
      cells and sperm chromatin structure in mice].
AB  - OBJECTIVE: To study the effects of 50 Hz electromagnetic fields (EMFs) on DNA of
      testicular cells and sperm chromatin structure in mice. METHODS: Mice were
      exposed to 50 Hz, 0.2 mT or 6.4 mT electromagnetic fields for 4 weeks. DNA strand
      breakage in testicular cells was detected by single-cell gel electrophoresis
      assay. Sperm chromatin structure was analyzed by sperm chromatin structure assay
      with flow cytometry. RESULTS: After 50 Hz, 0.2 mT or 6.4 mT EMFs exposure, the
      percentage of cells with DNA migration in total testicular cells increased from
      the control level of 25.64% to 37.83% and 39.38% respectively. The relative
      length of comet tail and the percentage of DNA in comet tail respectively
      increased from the control levels of 13.06% +/- 12.38% and 1.52% +/- 3.25% to
      17.86% +/- 14.60% and 2.32% +/- 4.26% after 0.2 mT exposure and to 17.88% +/-
      13.71% and 2.35% +/- 3.87% after 6.4 mT exposure (P < 0.05). Exposure to EMFs had
      not induced significant changes in S.D.alphaT and XalphaT, but COMPalphaT (cells
      outside the main population of alpha t), the percentage of sperms with abnormal
      chromatin structure, increased in the two exposed groups. CONCLUSION: 50 Hz EMFs
      may have the potential to induce DNA strand breakage in testicular cells and
      sperm chromatin condensation in mice.

PMID- 16405772
TI  - [Stress and mental health of farmer-workers].
AB  - OBJECTIVE: To study the farmer-workers'stress, their mental health and the effect
      of stress on mental health. METHODS: The Stressors Scale and SCL-90 were used for
      the test in a sample of 500 farmer-workers. RESULTS: The primary mental stressors
      of the farmer-workers were economic burden, protection of their rights and
      interests and working condition & load. There was difference in the degree of
      stress among the age groups and the groups of the degree of education. Farmer
      workers under 29 years old experienced the most mental stress, those between 30
      years old and 39 years old experienced less, and those above 40 years old
      experienced the least mental stress. In the Interpersonal Relationship Stress
      Scale, the scores of those with senior middle school education or above were
      higher than those with junior middle school education or even illiterate. But the
      scores in all other stress scale and the total stress scores were different: the
      scores of those illiterate and those with senior middle school education or
      above, were higher than those with junior middle school education or lower. The
      mental health status of the farmer-workers was lower than the norm. The farmer
      workers with at least one positive symptom factor accounted for 12.30% with the
      detectable rate of the factors of SCL-90 ranging from 1.9% to 6.5%. Most
      stressors could predict the mental health of the farmer-workers positively and
      remarkably. CONCLUSION: Some farmer-workers have mental disorders. Mental stress
      plays an important role in the mental health of the farmer-workers.

PMID- 16405773
TI  - [Investigation on an accident of hydrogen sulfide].

PMID- 16405774
TI  - [Relationship between millimeter wave irradiation in pregnant mice and c-Fos
      protein expression in hippocampus and learning and memory functions in their
      offsprings].
AB  - OBJECTIVE: To determine the threshold of millimeter wave irradiation for fetal
      injury in mice and the mechanism of decrease of learning and memory function in
      their offsprings and to verify whether the millimeter wave has the non-thermal
      effect. METHODS: Pregnant mice were irradiated by millimeter wave with
      frequencies of 37.4, 42.2, 53.0 and 60.0 GHz at power densities of 1, 3, 5, 8
      mW/cm(2) for two hours daily from the 6th to 15th day of their gestation.
      Learning and memory functions of their offsprings were tested by a Y-type
      electric maze. c-Fos protein expression level in hippocampus of their offsprings
      was determined with immunohistochemistry 0, 30, 60, 90 and 120 minutes after the
      offsprings were trained respectively. RESULTS: The minimal power density of
      millimeter wave for the decrease in learning and memory function and decrease of
      c-Fos protein expression level in hippocampus of their offsprings caused by 37.4,
      42.2 GHz and 53.0, 60.0 GHz was 5 and 3 mW/cm(2). Severity of injury for learning
      and memory in offsprings caused by irradiation increased with the power density
      of millimeter wave. The millimeter wave did not cause increase of the body
      temperature of the pregnant mice. CONCLUSION: The threshold of millimeter wave
      with 37.4, 42.2 GHz, and 53.0, 60.0 GHz causing fetal injury in mice is 5 and 3
      mW/cm(2) respectively. The decrease in learning and memory functions in offspring
      mice is related with decrease of c-Fos protein expression level in hippocampus.
      Millimeter wave has the non-thermal effects.

PMID- 16405775
TI  - [Observation of the L929 cell membrane after infrasound exposure with atomic
      force microscope].
AB  - OBJECTIVE: To observe the changes of L929 cell membrane with atomic force
      microscope (AFM) after infrasound exposure and to explore the mechanisms of
      effect of infrasound on cell membrane. METHODS: After primary culture, the L929
      cells were exposed to infrasound with intensity output of 130 dB and frequency of
      16 Hz 2 hours each day for 3 days. The subsequent changes in the membrane of the
      control cells and the cells exposed to the infrasound were determined by nano
      scale scanning with AFM. RESULTS: After infrasound exposure, the normal
      prominence of the membrane became short and the dent became shallow in the 7.5
      microm x 7.5 microm and 4.0 microm x 4.0 microm photographs. The prominence
      appeared as cobblestones. The surface of the membrane became smooth. CONCLUSION:
      The membrane structure of the L929 cells can be changed by infrasound exposure
      with intensity of 130 dB and frequency of 16 Hz. The change might be one of the
      characteristics of effect of infrasound on cell membrane.

PMID- 16405776
TI  - [Study on differential proteomic expression in human liver cells stimulated by
      trichloroethylene with proteomics].
AB  - OBJECTIVE: To explore the differential proteomic expression in human liver cells
      L-02 induced by different dosages of trichloroethylene (TCE). METHODS: Human
      liver cells L-02 were treated with different concentrations of TCE and the
      solvent control (dimethylsulfoxide). The total cellular proteins were separated
      using 2DE and visualized with silver staining after TCE treatment. The images
      were analyzed with Image Master 2D Platinum 5.0 analysis software. The
      differentially expressed protein spots were identified by matrix assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF-TOF-MS).
      RESULTS: Fifteen protein spots with significant difference were found, and went
      upward or downward or disappeared after the stimulation of TCE with different
      dosages, which indicated that TCE induced the change of the proteomic expression
      in the liver cells. The mass spectrum identification and the IPI human database
      retrieval were used for identifying 9 proteins related to the L-02 Liver cells
      induced by TCE. CONCLUSION: The result provides an insight to TCE-related
      molecular mechanism and which might be useful for further study of the TCE
      associated proteins and molecular markers.

PMID- 16405777
TI  - [Striated muscular injury and myocardiac injury caused by acute carbon monoxide
      poisoning].
AB  - OBJECTIVE: To investigate the incidence of rhabdomyolysis, the relationship
      between striated muscular injury and myocardiac injury, and the role of elevated
      serum creatine kinase (CK) played in screening these two complications following
      acute carbon monoxide poisoning (ACOP). METHODS: 280 patients with ACOP from
      January 2001 to April 2003 were analyzed retrospectively. According to the
      clinical manifestations of striated muscular injury (swelling, pain or serious
      myasthenia), the patients were divided into two groups: the evident injury group
      and non-evident injury group. RESULTS: The abnormality rate of electrocardiogram
      (ECG) and cardiac troponin I (CTnI) in the evident injury group (43 patients)
      were significantly higher than in the non-evident injury group (73.8% vs 43.4%, P
      < 0.001; 77.8% vs 20.9%, P < 0.001). There was a positive correlation between
      peak CK and MB isoenzyme (CK-MB) in both groups, respectively (r = 0.819, r =
      0.795, P < 0.01). There was no correlation in the evident injury group (P > 0.05)
      and only negative correlation in the non-evident injury group (r = -0.298, P <
      0.01) between peak CK and MB ratio (CK-MB/CK). Multiple regression analysis
      indicated that peak CK and CK-MB were only related with the striated muscular
      injury and were not affected by the indexes of the myocardial injury (ECG and
      CTnI); Both peak CK and CK-MB were positively correlated with the coma time
      before consultation in the non-evident injury group and the latter was also
      affected by CTnI. The incidence of positive muscular injury symptoms increased
      with the elevation of CK activity. There was no significant difference either in
      the ECG abnormality rate between the < 5 times elevated CK level subgroup and the
      > 5 times elevated CK level subgroup (P > 0.05), or in the CTnI positive rate
      between the normal CK level subgroup and the < 5 times elevated CK level subgroup
      (P > 0.05). CONCLUSION: Striated muscular injury is not a rare complication of
      ACOP, and always accompanied by myocardial injury. The strikingly elevated serum
      level of CK in patients with ACOP might be more likely to indicate the striated
      muscle not myocardiac injury.

PMID- 16405778
TI  - [Clinical characteristics, CT and MRI findings for delayed encephalopathy after
      acute carbon monoxide poisoning].
AB  - OBJECTIVE: To investigate clinical and imaging characteristics of delayed
      encephalopathy after acute carbon monoxide poisoning (DEACMP) and their
      relationship to the prognosis. METHODS: The clinical, CT and MRI findings in 46
      patients with DEACMP were analysed and compared. RESULTS: The main manifestations
      of the disease were mental and extrapyramidal impairment. CT scan showed diffuse
      low density changes in bilateral cerebral white matter, bilateral or unilateral
      globus pallidus or basal ganglia areas. The MRI showed necrosis and degeneration
      of glodus pallidus and cerebral white matter demyelination mainly around the
      ventricles, with high signal intensity in T(2)-weighted and equal or low signal
      intensity in T(1)-weighted as well as the lesions in hippocampus and brain stem.
      There was the sign of encephalatrophy in the late stage. The positive detectable
      rate of MRI was 82.1%, higher than that of CT, 43.2%. MRI was more sensitive than
      CT. CONCLUSION: The prognosis of the patients is closely related with the age,
      time of come after DEACMP and the effectiveness of treatment. Both CT and MRI are
      valuable in the diagnosis and evaluation of the prognosis for DEACMP. MRI is more
      sensitive than CT in the diagnosis of DEACMP.

PMID- 16405779
TI  - [Protective effects of total flavonoids of Broussonetia papyrifera on oxidative
      injury of ultraviolet A to human keratinocytes].
AB  - OBJECTIVE: To investigate the oxidative damage of ultraviolet A (UVA) to human
      immortalized keratinocytes line HaCaT and the protective effects of total
      flavonoids of Broussonetia papyrifera (TFBP) gotten from the leaves of
      broussonetia papyifera. METHODS: Based on the culture of the human keratinocytes,
      the experiment group added with different dosages of TFBP before exposure to the
      radiation, received the UVA radiation together with the treatment group. The
      levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-Px) were determined in cultured HaCaT cells as
      well as the cell activity with MTT reduction assay. Human immortalized
      keratinocytes HaCaT cells received ultraviolet A with the different dosages
      between 0.46 and 2.76 J/cm(2) respectively. The protective effects of TFBP at
      different concentrations were also evaluated. RESULTS: The cell activity
      decreased gradually from 96.3% to 37.5% with the increase of UVA dosage from 0.46
      J/cm(2) to 2.76 J/cm(2). After 10 mg/L up to 200 mg/L of TFBP were added the cell
      activity increased, the levels of MDA decreased from (5.14 +/- 0.58) nmol/mg pro
      to (2.98 +/- 0.14) nmol/mg pro, the levels of SOD increased from (23.09 +/- 3.91)
      U/mg pro to (34.50 +/- 1.59) U/mg pro and the activity of GSH-Px increased
      somewhat. CONCLUSION: Ultraviolet A causes significant oxidative injury to HaCaT
      cells under the conditions of this study. TFBP gotten from the leaves of
      broussonetia papyrifera has certain protective effect on HaCaT epithelial cells.

PMID- 16405780
TI  - [Study on the work ability and its effect factors among health professionals].

PMID- 16405781
TI  - [Investigation on sensitivity of mites of acaro-asthma patients in different
      jobs].

PMID- 16405782
TI  - [Health of workers exposed to dimethylformamide].

PMID- 16405783
TI  - [Effects of antineoplastics drug on T-lymphocytes subsets in nurses of
      occupational exposure to antineoplastic drugs].

PMID- 16405784
TI  - [Effects of 50 Hz electromagnetic fields on the c-fos mRNA expression of early
      mouse embryos].

PMID- 16405785
TI  - [Role of heat shock protein 70 expression in DNA damage induced by 7, 8
      dihydrodiol-9, 10-epoxide-benzo(a)pyrene].

PMID- 16405786
TI  - [Study on immunocyte proliferation and DNA damage induced by lead in mice].

PMID- 16405787
TI  - [Clinical observation and ultrasonic imaging characteristic of acute poisonous
      mushroom poisoning].

PMID- 16405788
TI  - [Change of the serum interleukin 6 in patients with delayed encephalopathy after
      acute carbon monoxide poisoning].

PMID- 16405789
TI  - [Investigation on an accident of n-hexane poisoning in a shoes factory].

PMID- 16405790
TI  - [Eleven cases of acute phenylamines poisoning].

PMID- 16405791
TI  - [Thirteen cases of oral peroxide acid poisoning].

PMID- 16405793
TI  - [Eight cases of encephalopathy induced by ethylene dichloride].

PMID- 16405792
TI  - [Clinical analysis of occupational methanol poisoning of three cases].

PMID- 16405794
TI  - [One case of acute severe bromadiolone poisoning].

PMID- 16405795
TI  - [One case of myocardial damage induced by chlorine dioxide poisoning].

PMID- 16405796
TI  - [Eight cases of chronic severe liver diseases in workers exposed to
      dimethylformamide].

PMID- 16405797
TI  - [One case of Daphne punch oil af-2 as poisoning].

PMID- 16405798
TI  - [Clinical analysis of multiple organ damage in acute severe ethylene oxide
      poisoning].

PMID- 16405799
TI  - [Study progress on irritant contact dermatitis].

PMID- 16405800
TI  - [Epidemiological progress on acute occupational hand injury].

PMID- 16405801
TI  - [Occupational allergies induced by industrial enzyme].

PMID- 16405802
TI  - [Two cases of mercury poisoning].

PMID- 16405805
TI  - [Discussion on WBGT index].

PMID- 16405804
TI  - [Investigation on an accident of chlorine dioxide poisoning].

PMID- 16405806
TI  - [Evaluation on the result of reducing noise in towboat engine room].

PMID- 16405808
TI  - [Underestimation of the harm of sleep apnea to cardiovascular diseases is not
      tolerable].

PMID- 16405807
TI  - [Universal prophylaxis-therapy of sleep apnea].

PMID- 16405809
TI  - [Sleep apnea and dysfunction of respiratory regulation].

PMID- 16405810
TI  - [Treatment of obstructive sleep apnea syndrome in children].

PMID- 16405811
TI  - [Relationship between respiratory pattern and craniofacial growth and development
      in children].

PMID- 16405812
TI  - [Clinical features of early-onset narcolepsy].
AB  - OBJECTIVE: To investigate the clinical features of early onset narcolepsy.
      METHODS: The clinical data of 105 consecutive patients with narcolepsy, 63 of
      which with an onset age of 9.7 +/- 3.1 on average and 42 with an onset age of
      22.8 +/- 9.3 on average. Interrogation, physical examination, CT, and MRI were
      carried out. Polysomnography was conducted. Then the data were compared between
      these 2 groups. RESULTS: All 105 patients showed daytime sleepiness. The
      incidence rate of cataplexy was 92% in the early onset group, significantly
      higher than that of the late onset group (P = 0.023). There were no significant
      differences in the rates of sleep paralysis, hypnagogic hallucination, and
      disturbed nocturnal sleep. Multiple sleep latency test showed that the mean sleep
      latency of the early-onset group was 4.5 +/- 4.0 min, significantly shorter than
      that of the late onset group (7.0 +/- 5.7 min, P = 0.018); the REM sleep latency
      of the early onset group was 3.4 +/- 3.2 min, significantly shorter than that of
      the late onset group (4.8 +/- 2.2 min, P = 0.02). The number of REM sleep of the
      early onset group was 3.4 +/- 2.0, significantly more than that of the late onset
      group (2.5 +/- 1.9, P = 0.09). The apnea and hypopnea index of the late onset
      group was 9.2 +/- 16.5, significantly higher than that of the early onset group
      (1.9 +/- 6.3, P = 0.009). The 3 cases of narcolepsy with family history were all
      cases of early onset narcolepsy. CONCLUSION: Early onset narcolepsy patients have
      more severe daytime sleepiness and higher rate of cataplexy. The pathogenesis of
      early onset narcolepsy may be more closely associated with genetic factors.

PMID- 16405813
TI  - [Pharyngeal size and collapsibility in patients with obstructive sleep apnea
      hypopnea syndrome].
AB  - OBJECTIVE: To study the pharyngeal cross-sectional area and collapsibility among
      the patients with obstructive sleep apnea hypopnea syndrome (OSAHS), simple
      snorers, and normal persons. METHODS: 171 patients with OSAHS, 44 with mild, 51
      with moderate, and 56 with severe OSAHS, 47 simple snorers, and 47 healthy
      subjects underwent upper airway cross-sectional area measurement using acoustic
      pharyngometer at the conditions of functional residual capacity (FRC) and
      residual volume (RV) in the upright sitting position. RESULTS: When the lung
      volume decreased from the condition of FRC to the condition of RV the pharyngeal
      cross-sectional area decreased from 2.63 cm(2) +/- 0.42 cm(2) to 1.96 cm(2) +/-
      0.35 cm(2) for the simple snorers, 2.70 cm(2) +/- 0.44 cm(2) to 1.78 cm(2) +/-
      0.39 cm(2) for the mild OSAHS patients, from 2.62 cm(2) +/- 0.52 cm(2) to 1.79
      cm(2) +/- 0.37 cm(2) for the moderate OSAHS patients, and from 2.57 cm(2) +/-
      0.46 cm(2) to 1.75 cm(2) +/- 0.40 cm(2) for the severe OSAHS patients, all with
      higher decrease rates (33.93% +/- 11.81%, 31.13% +/- 10.76%, and 31.31% +/-
      13.44%) than that of the normal persons (25.07% +/- 10.39%), smaller than that
      for the normal persons (21.11% +/- 8.19%, from 3.05 cm(2) +/- 0.6 cm(2) to 2.38
      cm(2) +/- 0. 47 cm(2), all P < 0.05). The change ratios of the 3 OSAHS groups
      were significantly higher than that of the simple snorer group (all P < 0.01).
      This indicated that the pharynges of OSAHS patients were more collapsible.
      CONCLUSION: Snorers with or without apnea have smaller pharyngeal cross-sectional
      area than nonsnorers. The collapsibility of the upper airway is greater in both
      OSHAS patients and simple snorers than in healthy subjects.

PMID- 16405814
TI  - [Clinical value of TS90% in evaluation of hypoxemia in patients with obstructive
      sleep apnea/hypoventilation syndrome].
AB  - OBJECTIVE: To explore the appropriate study how to properly evaluate the
      hypoxemia degree in patients with obstructive sleep apnea/hypoventilation
      syndrome (OSAHS). METHODS: polysomnography was conducted on 108 OSAHS patients
      and 37 simple snorers to record the minimum oxygen saturation level (MiO(2)) and
      the total recorded time spent below 90% oxygen saturation (TS90%). The
      correlation between MiO(2) and the percent of the total recorded time spent below
      90% oxygen saturation (TS90%) with the AHI were calculated. RESULTS: The value of
      TS90% was significantly increased, and the value of MiO(2) was significantly
      decreased as the severity of OSAHS increased (all P < 0.001). The correlation
      coefficients of TS90% with AHI and with Epworth sleepiness scale (ESS) were both
      much higher than those of MiO(2). CONCLUSION: TS90% can express the severity of
      hypoxemia of the OSAHS patients more correctly than MiO(2). TS90% combined with
      MiO(2) can comprehensively and objectively reflect the severity of hypoxia of the
      OSAHS patients.

PMID- 16405815
TI  - [Multianalysis of short-term prognostic factors in surgical practices for
      hypertensive intracerebral hemorrhage].
AB  - OBJECTIVE: To evaluate and compare the effectiveness of different types of
      surgical therapy for patients with hypertensive cerebral hemorrhage, and analyze
      the major risk factors of prognosis. METHODS: 2464 patients with hypertensive
      cerebral hemorrhage in 92 hospitals in different areas of China underwent
      different types of surgical treatment: Group I (n = 639), undergoing traditional
      craniotomy as control; Group II (n = 409), receiving minimally invasive hematoma
      evacuation; and Group III (n = 1416), receiving CT guided stereotaxic hematoma
      aspiration. The clinical data were collected and underwent multianalysis.
      RESULTS: The factors influencing the short-term prognosis were Glasgow coma scale
      (GCS) score before surgery and the incidence of postoperative complications in
      Group II; GCS score before surgery and the incidence of postoperative
      complications and volume of hemorrhage, duration between ictus and surgery, use
      of urokinase in Group III; and GCS score before surgery, muscle power before
      surgery, diastolic pressure at admission and postoperative complications in Group
      III. CONCLUSION: Analysis of prognosis related factors of cerebral hemorrhage
      plays a very important role in the selection of therapeutic strategy. It may be
      beneficial for standardizing surgical indications, further designing large scale
      clinical trial, helping the doctors select appropriate strategy of treatment, and
      serving the social population better.

PMID- 16405816
TI  - [Endoscopic decompression of optic canal].
AB  - OBJECTIVE: To evaluate the effectiveness of endoscope in the treatment of optic
      nerve injury. METHODS: Thirteen patients with fracture at the inner and lower
      walls of optical canal underwent endoscopic decompression. The posterior 1/3 of
      the middle concha, the posterior ethmoid sinus and sphenoid sinus were opened,
      chips of bone and old hematocele were scavenged, and the optic ring of the optic
      canal was polished; however, the sheath of the optic nerve remained intact. In 2
      cases with the dura broken at the cranial part of optic nerve, the broken site
      was covered with mucosa of middle concha, and the sphenoid sinus and the middle
      nasal meatus were covered with oil ribbon gauze. Three days after the operation,
      the ribbon gauze was pulled put, however, if cerebro-spinal fluid leakage was
      suspected, the ribbon gauze was pulled out 7-10 days after. After the operation
      the visual acuity improvement reaching one grade or more and improvement of
      visual field were defined as effective. RESULTS: Five of the 6 patients without
      light perception before the operation showed improvement in visual acuity. The
      other 7 patients with residual visual acuity all recovered to different extents.
      CONCLUSION: A mini-invasive surgery, decompression of optic canal with endoscope
      is effective in decompressing optic nerve, decreasing the injury of optic nerve,
      and the patients recover quickly after operation.

PMID- 16405817
TI  - [Impacts of donor and recipient's SNP of cytokine and cytokine receptor on early
      acute renal allograft rejection].
AB  - OBJECTIVE: To investigate the impact of donor and recipient's SNP of cytokine and
      cytokine receptor on early acute rejection after renal transplantation. METHODS:
      (1) 129 cases of cadaveric renal allograft recipients were divided into two
      groups according to the presence or absence of acute graft rejection. The
      distribution of 21 single nucleotide polymorphisms in cytokines and cytokine
      receptors gene were compared between two groups as well as latent factors
      affecting the development of acute rejection. (2) Based on the result of HLA-DR
      matching between donor and recipient, the recipients with AR were stratified into
      two conditions, 0-1 locus mismatched (0-1MM) and completely mismatched (2MM). By
      aids of SPSS 11.5 software, association analysis was assessed using Kruskal
      Wallis test, 2 x 2 or 2 x n contingency table, the Chi-square test. RESULTS: (1)
      Of 129 recipients of renal transplantation, 39 developed acute graft rejection
      (30.2%). (2) Compared with recipients without acute rejection, the number of HLA
      DR mismatching was significantly higher in rejection group. (3) In rejection
      group and non-rejection group, the gene polymorphism distribution was
      significantly different. (4) 0-1MM group and 2MM group were various in the gene
      polymorphism distribution. CONCLUSIONS: In the whole, the susceptibility of acute
      rejection after renal transplantation may be predicted by the donor and
      recipient's SNP of cytokine and cytokine receptor.

PMID- 16405818
TI  - [Dendritic cells reduce the number and function of CD4+CD25+ cells in cytokine
      induced killer cells].
AB  - OBJECTIVE: To investigate the influence of dendritic cells (DCs) on the
      prevalence and function of regulatory T cells (Tregs) in cytokine induced killer
      (CIK) cells. METHODS: The blood samples of 20 patients with solid tumors were
      collected. The peripheral mononuclear cells (PBMCs) were isolated. CIK cells were
      added into the culture fluid without CD(4)(+)CD(25)(+)T cells (CIK-Treg(del)
      cells) and the culture fluid of regular PBMCs respectively, and the proliferation
      and cytotoxicity of the CIK cells were detected by BrdU method and with the cells
      of human lung carcinoma, breast carcinoma, colon carcinoma, and lymphoma as
      target cells respectively. CD(4)(+)CD(25)(+)T cells were added into another
      culture fluid of CIK-Treg(del) cells at the proportions of 20:1, 10:1, and 5:1
      respectively, then the proliferation and cytotoxicity of the CIK cells were
      detected as described above. Flow cytometry was used to detect the surface
      markers of CIK cells. To identify the influence of DCs on the anti-tumor activity
      of CIK, PBMCs were isolated from the patients with solid tumor to culture the DCs
      and CIK cells. Dendritic cells were harvested on day 7 and co-cultured with the
      CIK cells (DC+CIK cells). The frequency of Tregs in CIK was determined by flow
      cytometry. The cytotoxicity was examined by LDH assay. The levels of TGF-beta, IL
      10, IFN-gamma, IL-2, and IL-6 were analyzed by ELISA. RESULTS: The rates of the
      main effector cells in CIK cells (CD(3)(+)CD(56)(+) cells) were 17% +/- 5% and
      28% +/- 5% in the regular CIK cells and CIK-Treg(del) cells respectively. LDH
      method showed that the cytotoxicity towards tumor cells of the CIK-Treg(del)
      cells The rates of the main effector cells in CIK cells (CD(3)(+)CD(56)(+) cells)
      were 17% +/- 5% and 28% +/- 5% in the regular CIK cells and CIK-Treg(del) cells
      respectively. LDH method showed that the cytotoxicity towards tumor cells of the
      CIK-Treg(del) cells was higher than that of the regular CIK cells (P < 0.05),
      however, after the addition of selected cells, the cytotoxicity of the CIK
      Treg(del) cells decreased. Flow cytometry showed that the proportions of
      CD(4)(+)CD(25)(+) Treg cells in the CIK cells and DC-CIK cells were 13% +/- 5%
      and 10% +/- 4% respectively (t = 3.977, P = 0.001). After the DC induction the
      cytotoxicity of CIK cells was significantly higher than that of the regular CIK
      cells. ELISA showed that after DC induction the levels of TGF-beta and IL-10 of
      the DC+CIK group were significantly lower than those of the regular CIK cells (t
      = 2.136, P = 0.046; and t = 2.965, P = 0.008), and the level of IFN-gamma was
      significantly higher in the DC+CIK group (t = 2.220, P = 0.039). CONCLUSION:
      CD(4)(+)CD(25)(+) regulatory T cells inhibit the anti-tumor activity of CIK
      cells. The interaction between CIK cells and DCs is sufficient for the blockage
      of the properties of regulatory T cells. CIK cells have the desirable properties
      for immunotherapy approaches, especially after co-culture with DCs.

PMID- 16405819
TI  - [Electrophysiological influences of gamma knife at different doses on the
      compressed cat optic nerve].
AB  - OBJECTIVE: To investigate the electrophysiological influences of gamma knife at
      different doses on the compressed cat optic nerve. METHODS: Model of compressed
      optic nerve was established in 20 cats. Two months later, the 20 cats were
      randomly divided into 5 equal groups. Four groups accepted the irradiation of
      gamma knife at the dose of 10, 11, 12, and 13 Gy respectively. One group was used
      as controls. Pattern visual evoked potential examination was used 3 days, 1 week,
      half a month, and 1, 2, 3, 4, and 5 months after the beginning of irradiation.
      RESULTS: Electrophysiological changes could be observed 1 week later began to
      recover half a month later and then gradually recovered to normal with the lapse
      of time. Irreversible electrophysiological changes were observed in the groups
      undergoing gamma knife at the doses of 11 Gy and over, and these changes
      aggravated with the lapse of time. CONCLUSION: 10 Gy is the minimum dose of gamma
      knife that cause beneficial electrophysiological changes in the compressed cat
      optic nerves. The minimum dose that causes irreversible damage is 11 Gy.

PMID- 16405832
TI  - [Epidemiology of medical error is supposed to spring up in China].

PMID- 16405831
TI  - [Attach importance to the research of criterion of treatment in prostate cancer].

PMID- 16405834
TI  - [Proteomic analysis of prostate cancer using surface enhanced laser
      desorption/ionization mass spectrometry].
AB  - OBJECTIVE: To identify the serum biomarkers of prostate cancer by using protein
      chip and bioinformatics. METHODS: Eighty three prostate cancer (PCA) patients and
      ninety five healthy people from mass screen in Changchun were detected by surface
      enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The data of
      spectra were analyzed by bioinformatics tools-Biomarker Wizard and Biomarker
      Pattern. RESULTS: Compared with the spectra of healthy people, there were 18
      potential markers detected in the spectra of the PCA patients, the protein
      expression was high in 4 of which and low in the 10 of which. The softwares
      Biomarkerwizard and Biomarker Pattern automatically, under given conditions,
      selected 8 biomarker proteins to be used to establish a five layer decision tree
      differentiate to diagnose PCA and differentiate PCA from healthy people with a
      specificity of 92.632% and a sensitivity of 96.386%. CONCLUSION: New serum
      biomarkers of PCA have been identified, and this SELDI mass spectrometry coupled
      with decision tree classification algorithm will provide a highly accurate and
      innovative approach for the early diagnosis of PCA.

PMID- 16405835
TI  - [Amelioration of latent skin lesions in streptozotocin-induced diabetic rats by
      insulin].
AB  - OBJECTIVE: To explore the latent skin lesions in streptozotocin-induced diabetic
      rats and the mechanism of insulin prevention. METHODS: 81 male Sprague-Dawley
      (SD) rats were randomized into control (C, n = 27) and STZ-induced diabetic
      groups (n = 54), and then the diabetic rats were randomized into 2 groups: Group
      A group (n = 27) that was treated with insulin enough to control the high
      concentration of blood glucose strictly, and Group B group (n = 27) in which
      insulin was given too nut not sufficient to control the high blood glucose.
      Twenty-seven normal rats were used as controls. Four, eight, and twelve weeks
      after STZ-induction, skin specimens from the back were collected to undergo
      hematoxylin-eosin staining and histological examination. The skin glucose content
      was measured by Beckman's autoanalyzer. The skin advanced glycation end products
      (AGEs) concentration was assessed by fluorescence spectrophotometry and
      immunohistochemistry. The ultrastructure changes of skin microvessel were
      observed by electron microscopy. RESULTS: Twelve weeks after the establishment of
      the DM model the skin thickness of Group B was decreased, the features of
      multilayer epithelium structure disappeared in epidermis, and part of the
      collagen fibers in dermis became atrophic, swollen and degenerated, infiltration
      of inflammatory cells to different degrees was found, and subcutaneous fat showed
      progressive atrophy or disappeared. However, such changes were not detected in
      Group A. The skin glucose contents of Group B at different time points were all
      higher than those of Group A and Group (all P < 0.01) without a significant
      difference between Groups A and C. The fluorescence values of skin collagen
      extracts of Groups A and B were significantly higher than that of normal rats.
      The 8-week fluorescence value of skin collagen extracts of Groups B was 34 U/mg
      +/- 4 U/mg, significantly higher than that of Group A (29 U/mg +/- 3 U/mg, P <
      0.05). The 12-week fluorescence value of skin collagen extracts of Groups B was
      41 U/mg +/- 4 U/mg, significantly higher than that of Group A (32 U/mg +/- 4
      U/mg, P < 0.05). The 8-week AGEs positive expression rate of Group B was 32% +/-
      4%, significantly higher than that of Group A (25% +/- 5%, P < 0.05), and the 12
      week AGEs positive expression rate of Group B was 39% +/- 5%, significantly
      higher than that of Group A (27% +/- 4%, P < 0.05). Degeneration of endothelial
      cells and thickening of basement membrane were more markedly in Group B than in
      Group A. CONCLUSION: Accumulation of AGEs in skin and high concentration of
      glucose are important causes of diabetic skin complications. Insulin application
      at the early stage postpones the course of diabetic skin lesions with the
      possible mechanisms of lowering the high glucose, inhibiting AGEs synthesis, and
      blocking the action of AGEs.

PMID- 16405836
TI  - [Single nucleotide polymorphisms of HIV coreceptor CCR5 gene in Chinese Yi ethnic
      group and its association with HIV infection].
AB  - OBJECTIVE: To investigate the single nucleotide polymorphism (SNP) of HIV-1
      coreceptor CCR5 gene in Chinese Yi ethnic group and the association between these
      SNPs and HIV/AIDS. METHODS: Peripheral blood samples of 102 HIV negative persons
      of Chinese Yi nationality, 87 males amd 15 females, aged 23 (12-37), and 68 HIV
      carriers, 61 males and 7 females, aged 27 (17-51). The regulatory and structural
      regions of the HIV coreceptor CCR5 gene were amplified from the genomic DNA by
      nested PCR, each of the two regions was divided into three gene fragments which
      were overlapped. High throughput DHPLC was used for screening of unknown
      mutations in each gene fragment. The PCR products showing different peak traces
      from wild types in DHPLC were sequenced by forward and reverse primers
      respectively. The sequences were analyzed with the help of Sequence Navigator
      software to search for SNP loci. Statistical analysis by SPSS and PPAP softwares
      were made to study the association between these SNPs and HIV infection. RESULTS:
      Five SNPs (A77G, G316A, T532C, C921T, and G668A) and a AGA deletion of the 686
      688 nucleotides were discovered in the coding region of this gene in Chinese Yi
      ethnic group. C921T mutation was a nonsense mutation, and the other SNPs (A77G,
      G316A, T532C, and G668A) are sense mutation, with the amino acid changes of K26R,
      G106R, C178R, and R223Q. Only the frequency of R223Q allelic gene was high (0.08)
      but those of the others were low (less than 0.01). There was no significant
      difference in the allele frequency between the HIV negative and HIV positive
      groups (all P > 0.05). Five SNP loci (T58934G, G59029A, T59353C, G59402A, and
      C59653T) were found in the regulatory region of CCR5 gene with high allelic
      frequencies of 0.1912-0.2941. Between the HIV negative and HIV positive groups,
      there were no differences in the SNP loc (all P > 0.05). Statistical analysis of
      the association between the linkage of mutation loci with HIV infection suggested
      a significant difference in the haplotype frequency of T59353C-G59402A between
      the HIV negative and HIV positive groups of the Yi population. CONCLUSION: A high
      throughput screening method of detecting unknown genetic mutation DHPLC can
      effectively analyze the SNP of CCR5 regulatory and structural regions in Chinese
      Yi ethnic group.

PMID- 16405837
TI  - [Analysis of ABL tyrosine kinase point mutations in imatinib treated chronic
      myelogenous leukemia patients].
AB  - OBJECTIVE: To evaluate ABL tyrosine kinase point mutations in imatinib treated
      chronic myelogenous leukemia (CML) patients. METHODS: A total of 45 bone marrow
      samples from 30 CML patients were included in this work. The patients were in
      accelerated/blast phase (AP/BP) or late-chronic phase (CP) at the start of
      imatinib and usually showed resistance to imatinib. ABL kinase domain of BCR-ABL
      allele was amplified by nested reverse transcriptase-polymerase chain reaction
      technique, followed by direct sequencing and sequence homologous analyzing.
      RESULTS: The ABL point mutation was detected in 13 of 30 patients, 12 of them had
      progressed to advanced phase, The other patient who was in late chronic phase
      showed point mutation when she was at 45th months of imatinib treatment, but she
      was still in complete cytogenetic remission at 50th months and is doing well. 4
      patients had Glu255Lys mutation and 4 had Gly250Glu, the other types of mutation
      were Phe359Cys, Glu355Gly, Met244Val, Tyr253His and Asp276Gly, each was tested in
      one patient. 11/12 patients who progressed to advanced disease and showed point
      mutation were collected samples in advanced stage, 8 patients showed homozygote
      mutation, and 3 patients had a mixture of wild and mutant type. In advanced stage
      patients, mutations were detected in a median of 5 months (ranged 0.5-30 months),
      it appeared much earlier than that in late CP patients (25.5 months, ranged 11-45
      months, P < 0.05). In 4/7 followed up patients, the intensity of point mutation
      increased gradually within 7-15 months before disease progression. 6 patients did
      not showed ABL point mutation while their disease were in progression.
      CONCLUSIONS: Abl kinase point mutation is one of the main mechanisms of CML
      secondary resistance to imatinib. Long term regular monitoring of ABL kinase
      point mutation is necessary during imatinib treatment.

PMID- 16405838
TI  - [A study on the significance of plasma thrombospondin1 in thrombotic
      thrombocytopenic purpura and the relationship between thrombospondin1 and von
      Willebrand factor cleaving protease (ADAMTS13)].
AB  - OBJECTIVE: To measure plasma thrombospondin1 (TSP1) in thrombotic
      thrombocytopenic purpura (TTP) and other diseases such as idiopathic
      thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), myocardial
      infarction, brain infarction, and malignant tumor et al. and 8 patients after
      bone marrow transplantation (BMT) were also investigated. Then to study on the
      relationship between TSP1 and von Willebrand factor cleaving protease (ADAMTS13);
      and to identify the significance of plasma TSP1 in TTP. METHODS: TSP1 was
      measured by a commercial kit and the activity of ADAMTS13 was evaluated by
      residue collagen binding assay. RESULTS: TSP1 in TTP plasma before plasma
      exchange or plasma infusion was 6.49 mg/L, and stepping up to 13.02 mg/L after
      therapy, but still significantly lower than 18.34 mg/L in normal control. While
      the decrease in different degree of ADAMTS13 activity was observed from 0%-52%,
      and there were 8 samples whose activity of ADAMTS13 were no more than 10%; the
      different extent of increase in those patients after therapy was demonstrated to
      be 2.9%-93.4%, only one patient's ADAMTS13 activity was below 10%. The activity
      of ADAMTS13 in some ITP and SLE patients were mildly decreased (63% +/- 16% and
      70% +/- 14% respectively), TSP1 were also decreased (16 mg/L +/- 8 mg/L). TSP1 in
      patients of myocardial infarction and brain infarction were increased (24.0 mg/L
      +/- 2.9 mg/L), while ADAMTS13 activity had no significant change (72% +/- 16%).
      Same things happened in BMT patients. CONCLUSION: There was some concordance
      between the decrease of ADAMTS13 activity and TSP1 in plasma of TTP patients. And
      the change of TSP1 was restricted to TTP. TSP1 may contribute to the episode of
      TTP in a still unclear fashions.

PMID- 16405839
TI  - [The protective effects to the function of kidney and long by clearing of
      cytokines in patients with open-heart surgery].
AB  - OBJECTIVE: To observe the effect of cytokines absorption on renal and respiratory
      function in patients with open-heart surgery. METHODS: 30 patients undergoing
      valve replacement with cardiopulmonary bypass (CPB) were randomly divided into
      two groups. A sulfonated polyacrylonitrile hemofilter (AN69) that has been used
      to absorb cytokines was connected into the efferent limb of CPB in Group A (n =
      15), and a cellulose triacetate hemofilter (CT 190G) instead of AN69 was used as
      controls (Group B, n = 15). The levels of plasma pro-inflammatory (TNF-alpha, IL
      6, IL-8) anti-inflammatory cytokines (IL-10, IL-1ra), C-reactive protein (CRP)
      levels, and post-operation renal and respiratory function were compared between
      the two groups. Blood samples were analysed for TNF-alpha and IL-6 and IL-8 and C
      reactive protein (CRP). The changes in renal, respiratory function were also
      observed. RESULTS: (1) At the end of CPB, TNF-alpha 10 ng/L +/- 3 ng/L and IL-6
      115 ng/L +/- 22 ng/L levels in Group A were significantly lower than that in
      Group B 13 ng/L +/- 3 ng/L, 134 ng/L +/- 29 ng/L) respectively (P < 0.05 in all).
      There is no statistical differences in plasma IL-10 and IL-1ra levels between the
      two groups. (2) After 24 hours of CPB, the magnitude of increased body
      temperature, heart rate, white blood cell and plasma CRP in Group A [1.6 degrees
      C +/- 0.2 degrees C, 15/min +/- 4/min, (17 +/- 3) x 10(9)/L, 56 mg/L +/- 13
      mg/L], were significantly lower than that in Group B [2.1 degrees C +/- 0.2
      degrees C, 23/min +/- 6/min, (22 +/- 3) x 10(9)/L, 69 mg/L +/- 15 mg/L]
      respectively (P < 0.05 in all). (3) After 24 hours of CPB, the levels of 24h
      urinary protein excretion and urinary N-acetyl-beta-D-glucosaminidase (NAG) were
      significantly lower in Group A when compared to that in Controls (0.20 g/d +/-
      0.08 g/d vs 0.30 g/d +/- 0.14 g/d, 28 U/L +/- 11 U/L vs 38 U/L +/- 13 U/L
      respectively), P < 0.05 in all. The level of creatinine clearance (Ccr) in Group
      A (68 +/- 7) ml.min(-1).1.73 m(-2) was significantly elevated than that in Group
      B (57 +/- 11) ml.min(-1).1.73 m(-2) (P < 0.05). (4) One hour after the end of
      CPB, the magnitude of increased plateau airway pressure (P(Plateau)) and peak
      airway pressure (P(Peak)) in Group A were significantly lower than that in
      Controls (P < 0.01 in all). The duration that need mechanical ventilation after
      operation in Group A (4.9 h +/- 0.6 h) was much shorter than that in Group B (5.8
      h +/- 0.8 h, P < 0.05). CONCLUSIONS: Lowering the plasma levels of cytokines by
      extracorporeal absorption may attenuate systemic inflammatory response and
      protect lung and kidney function in patients with open-heart surgery.

PMID- 16405840
TI  - [Effects of losartan, ramipril and their combination on left ventricular
      remodeling and function in spontaneous hypertensive rats].
AB  - OBJECTIVE: To evaluate the effects of losartan, an angiotensin receptor blocker,
      ramipril, an angiotensin converting enzyme inhibitor, and their combination on
      left ventricular remodeling and diastolic function in SHR at the same level of
      blood pressure. METHODS: Sixty-two SHRs and 20 WKYs were divided randomly into 5
      groups: WKY-control group, SHR-control group, SHR-ramipril group, SHR-losartan
      group, and SHR-combination group. Twelve weeks after feeding, 6 rats from each
      group were randomly selected to undergo hemodynamic examination and then killed
      to undergo further examinations, and 24 weeks after the remaining rats underwent
      the same examinations. The hemodynamic examination included the systolic blood
      pressure (SBP) of the caudal artery, left ventricular systolic pressure (LVSP),
      left ventricle end diastolic pressure (LVEDP), maximum uprising velocity of left
      ventricle pressure (dP/dtmax), and maximum declining velocity of left ventricle
      pressure (-dP/dtmax), and tau. Then the hearts were taken out to measure the
      weight of heart, undergo pathological examination, measure the intracellular free
      calcium concentrations, hydroxyproline concentration, interstitial collagen
      volume fraction (CVF), perivascular collagen area/luminal area (PVCA/LA), the
      mRNA expression of SR Ca(2+)-ATPase, phospholamban and L-type calcium channel,
      and the protein levels of SR Ca(2+)-ATPase. The myocardial ultrastructure was
      analyzed by electron microscopy. RESULTS: The speed, extent, and sustained time
      of blood pressure decrease were better in the combination group than in the other
      2 treatment groups. Twelve and 24 weeks after treatment the levels of LVM/BW in
      the combination group were significantly lower than those of the control group,
      however, without significant differences among the 3 treatment groups. The values
      of LVSP, LVEDP, and tau 12 and 24 weeks after treatment in the 3 treatment groups
      were all significantly lower and the levels of -dP/dtmax significantly higher
      than those of the control group (all P < 0.01). The values of CVF in the
      myocardium and PCVA/VA of the heart wall arteriole 12 and 24 weeks after in the 3
      treatment groups were significantly lower than those of the control group, and
      the CVF in the myocardium 12 weeks after in the combination group was
      significantly than that of the ramipril group. Microscopy showed that the degree
      of myocardial fibrosis in the 3 treatment groups were significantly milder than
      those of the control group, and the ultrastructure improvement improved along
      with the lapse of time in the sequence of combination group > losartan group >
      ramipril group. The concentrations of hydroxyproline in cardiac muscle cells of
      the 3 treatment 12 and 24 weeks after were significantly than those of the
      control group and decreased gradually time-dependently. The expression of Ca(2+)
      ATPase mRNA 24 weeks after of the ramipril, losartan, and combination groups were
      53.5%, 72.9%, and 76.7% higher than that of the control group, and the Ca(2+)
      ATPase protein expression of the 3 treatment groups were 28.9%, 33.3%, and 49.3%
      higher than that of the control group. The expression of L-type Ca(2+) channel
      mRNA of the 3 treatment groups were 51.8%, 76.8%, and 98.2% than that of the
      control group. CONCLUSION: Both losartan and ramipril reverse LVH and left
      ventricular diastolic dysfunction. A combination of these two drugs is more
      effective than single drug treatment for improvement of myocardial fibrosis and
      ultrastructure. All three-treatment groups can raise calcium-handling proteins
      mRNA and protein expressions, which may be the underlying molecular mechanisms
      for their therapeutic effects.

PMID- 16405841
TI  - [Up-regulation of thymidine phosphorylase and anti-angiogenesis by interferon
      alpha in human hepatocellular carcinoma cell line and xenograft].
AB  - OBJECTIVE: To further study the impact of interferon-alpha (IFN-alpha) on
      thymidine phosphorylase (TP) expression and angiogenesis. METHODS: Human
      hepatocellular carcinoma cells of the line SMMC-7721 were cultured and added with
      IFN-alpha of different doses: 0 (as control group), 1000, 5000 and 10,000 U/ml.
      Twenty-four hours later RT-PCR was used to detect the TP mRNA expression. Boyden
      chamber method was used to examine the endothelial cells migration. Suspension of
      SMMC-7721 cells was inoculated subcutaneously into 30 male BALB/c-nu/nu mice, the
      mice were randomly divided into 5 equal groups to be subcutaneously injected with
      IFN-alpha of different doses: 0 (as control group), 1.0 x 10(6), 3.0 x 10(6), 9.0
      x 10(6), and 1.5 x 10(7) U.kg(-1).d(-1) for 3 weeks. The eating behavior,
      activity, body weight, and tumor size were observed. The rats were killed 2 days
      after the drug injection was stopped. The subcutaneous tumors were taken out to
      undergo histological examination and TP protein expression by ELISA. The
      microvessel density (MVD) was detected using anti-CD34 monoclonal antibody.
      RESULTS: The TP mRNA expression of the SMMC-7721 cells induced by IFN-alpha of
      the doses of 5000 U/ml and 10,000 U/ml significantly increased in comparison with
      the un-treated SMMC-7721 cells (0 U/ml, P < 0.05). The endothelial cell migration
      significantly increased in the IFN-alpha 1000 U/ml group compared with the
      control group (P < 0.001), and then decreased along with the increase of IFN
      alpha dose; there were no significant differences in the epithelial migration
      among the groups of 0, 5000, and 10,000 U/ml IFN-alpha doses (all P > 0.05). The
      TP protein expression levels of the tumor in the rats treated with IFN-alpha of
      the doses of 9.0 x 10(6), and 1.5 x 10(7) U.kg(-1).d(-1) were 48 ng/mg +/- 24
      ng/mg and 60 ng/mg +/- 6 ng/mg respectively, 1.9 and 2.4 times that of the
      control group (both P < 0.01). The MVD of the tumors was 6.0 +/- 1.8 in the 9.0 x
      10(6) U.kg(-1).d(-1) IFN-alpha group, significantly higher than that of the
      control group (P < 0.01); and was 4.0 +/- 1.5 in the 1.5 x 10(7) U.kg(-1).d(-1)
      group, significantly lower than that of the 9.0 x 10(6) U.kg(-1).d(-1) group (P <
      0.05) and not significantly different from that of the control group. The tumor
      inhibiting rate of the 1.5 x 10(7) U.kg(-1).d(-1) IFN-alpha group was 68%,
      significantly higher than that of the untreated group (P < 0.05). CONCLUSION: IFN
      alpha of certain doses up-regulate the TP expression, and inhibit the
      angiogenesis induced by TP as well.

PMID- 16405842
TI  - [Anxiety and depression related to the symptoms of gastroesophageal reflux
      disease].
AB  - OBJECTIVE: To compare the differences in the psychological scale scoring among
      different subgroups reflux esophagitis (RE) and non-erosive reflux disease (NERD)
      and to explore the influence of mental factors on the pathogenesis of RE and
      NERD. METHODS: Two hundred and six patients with typical heartburn and acid
      regurgitation underwent endoscopy and esophageal pH monitoring and then were
      divided into 4 groups: RE+ group (n = 35, 24.3%) with RE and positive pH
      monitoring results, RH- group (n = 15, 30.0%) with RE and negative pH monitoring
      results, NERD+ group (n = 77, 40%), with NERD and positive pH monitoring results,
      and NERD- group (n = 79, 50.6%) with NERD and negative pH monitoring results that
      was re-divided into 2 subgroups according to the symptom index (SI): NERD-SI+
      group (n = 18, 22.8%) with positive symptom index and NERD-SI- group (n = 61,
      77.2%) with negative SI. The demographic data and body mass index (BMI) were
      investigated. The psychological questionnaires: Symptom Checklist 90 (SCL-90),
      and Hospital Anxiety and Depression Scale (HAD) were used. RESULTS: (1) Male
      patients were dominant in the RE group and RE+ subgroup, while female patients
      were dominant in the NERD group and NERD+ subgroup. The values of BMI of the RE
      group and RE+ subgroup were significantly higher than those of the NERD group and
      NERD+ subgroup. (2) The abnormal pH monitoring rate of the RE group was 70.0%,
      significantly higher than that of the NERD group (49.4%). The average DeMeester's
      score of the RE group was 39.3 (96.5), significantly higher than that of the NERD
      group 13.8 (33.6). The average DeMeester's score of the RE+ group was 68.1
      (95.2), significantly higher than that of the NERD+ group 40.1 (64.4). (3) 44.6%
      (29/65) of the patients presented depression and 36.9% (24/65) had anxiety, most
      of them were in mild or moderate degree. The scores of most items of each mental
      scale were significantly higher in the NERD- patients than in the NERD+ patients,
      especially in the NERD-SI- subgroup. CONCLUSION: The symptoms of RE+ and NERD+
      patients are associated with esophageal acid exposure and the acid reflux in the
      RE patients is much severer than that in the NERD patients. Anxiety and
      depression are related to the symptoms of patients without objective evidence of
      esophageal mucosal injury and acid reflux (NERD-), especially in the symptom
      index negative subgroup. Visceral hypersensitivity and stress play an important
      role in the pathogenesis of gastroesophageal reflux.

PMID- 16405844
TI  - [Infection frequency of Epstein-Barr virus in subgingival samples from patients
      with different periodontal status and its correlation with severity of
      periodontal lesion].
AB  - OBJECTIVE: To detect the infection frequencies of different Epstein-Barr virus
      (EBV) genotypes in subgingival samples of chronic periodontitis, and the
      correlation among infection with different genotypes and the severity of
      periodontal lesion. METHODS: Nested PCR (nPCR) with EBV-1 or EBV-2 specific
      primers was used to detect EBV-1 and EBV-2 in the subgingival samples from 65
      chronic periodontitis patients, 65 gingivitis patients and 24 periodontal healthy
      individuals. The amplicons were further identified by RFLP with endonucleases Afa
      I and Stu I. By using periodontal attachment loss (AL) and gingival index (GI) as
      the observing in, the correlation of infection with different EBV genotypes and
      the severity of periodontal lesion were analyzed. RESULTS: 0.01 ng of EBV-1 DNA
      could be detectable by the established nPCR. All the samples showed the same
      detection results by two separated nPCR. All the EBV-1 amplification products
      (497 bp) by using endonuclease Afa I digestion could be divided into two
      fragments with 355 bp and 142 bp respectively. After endonuclease Stu I
      digestion, all the EBV-2 amplification products (165 bp) displayed two fragments
      with 118 bp and 47 bp respectively. In the samples of chronic periodontitis
      patients, gingivitis patients, and healthy periodontal tissues, the positive
      rates were 28.5% (74/260), 16.9% (44/260), and 14.6% (14/96) for EBV-1; and were
      8.1% (21/260), 3.1% (8/260), and 0% for EBV-2 respectively, and the total EBV
      positive rates were 36.5% (95/260), 20.0% (52/260) and 14.6% (14/96)
      respectively. None of the positive samples was detectable for both the EBV-1 and
      EBV-2. The positive rates of EBV-1, EBV-2 and the total EBV positive rates in the
      chronic periodontitis samples were all higher than those in the gingivitis
      samples (all P < 0.05) and healthy periodontal tissue samples (all P < 0.01),
      without a significant difference between the gingivitis samples and healthy
      periodontal tissue samples (P > 0.05). Infection of EBV or EBV-1 or EBV-2 in CP
      patients could not be associated with AL or GI. CONCLUSION: Subgingival infection
      with either EBV-1 or EBV-2 is closely associated with chronic periodontitis.
      Infection of EBV may not correlate directly with severity of periodontitis.

PMID- 16405847
TI  - [Thulium laser resection of prostate-tangerine technique in treatment of benign
      prostate hyperplasia].
AB  - OBJECTIVE: To evaluate the safety and efficacy of thulium laser resection of
      prostate-tangerine technique (TmLRP) in treatment of benign prostate hyperplasia
      (BPH). METHODS: Thirty BPH patients, aged 74 (61-83), with a mean prostate volume
      of 58 ml, average international prostate symptom score (IPSS) of 19, and average
      maximum urinary flow (Q(max)) of 8.0 ml/s underwent TmLRP using 50 watt, 2.01
      microm Tm laser. The values of hematocrit, serum sodium, potassium, and chlorine
      concentrations, hemoglobin, Q(max), and IPSS before and 1 and 3 months after
      TmLRP were compared. RESULTS: The mean operating time was 56 minutes. No
      significant bleeding was found during operation. Post-operative bladder
      irrigation was no necessary. The urethral catheter was indwelled for 1-3 days
      post-operatively. There were not significant differences in values of hematocrit,
      serum sodium, potassium, and chlorine concentrations, and hemoglobin before and 1
      3 months after the operation. One month after the operation, the Q(max) was 23.1
      ml/s and IPSS was 7.9, and 3 months after the operation the was 24.7 ml/s and the
      IPSS was 7.1. By the end of 3-month follow-up no new cases of impotence and
      retrograde ejaculation had been found. CONCLUSION: TmLRP is a safe and efficient
      procedure in treatment of BPH.

PMID- 16405845
TI  - [Relationship of CTLA-4 exon 1 A49-->G polymorphism with sCTLA-4 and Th1/Th2 bias
      in idiopathic dilated cardiomyopathy].
AB  - OBJECTIVE: To investigate the association of cytotoxic T lymphocyte associated
      antigen-4 (CTLA-4) gene exon 1 A49-->G polymorphism with the genetic
      susceptibility to idiopathic dilated cardiomyopathy (IDC) in Chinese Han
      nationality. METHODS: Peripheral blood samples were collected from 48 patients
      with IDC, 31 males and 17 females, and 50 sex- and age-matched normal controls.
      ELISA was used to examine the cytokines: sCTLA-4, gamma-interferon (IFN-gamma),
      and interleukin-4 (IL-4)with the ratio of IFN-gamma/IL-4 as an indicator for
      Th1/Th2 bias. PCR-RFLP was used to analyze the A/G polymorphism of CTLA-4 exon 1
      A49-->G. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA
      4, IFN-gamma and IFN-gamma/IL-4 was evaluated by linear regression analysis.
      RESULTS: Compared with the normal controls, the frequencies of GG genotype
      (0.6042 and 0.7396, P = 0.012) and the G allele (0.36 and 0.56, P = 0.008) were
      significantly increased in the patients with IDC. Increased serum sCTLA-4 was
      found in the IDC group compared with the controls (1.87 microg/L +/- 1.06
      microg/L vs. 0.54 microg/L +/- 0.19 microg/L, P < 0.05). IFN-gamma was
      significantly lower in the IDC group than in the control group (16 ng/L +/- 6
      ng/L vs. 30 ng/L +/- 10 ng/L, P < 0.05). The ratio of IFN-gamma/IL-4 was
      significantly in the IDC group than in the control group (1.63 +/- 0.50 vs. 3.01
      +/- 0.89, P < 0.05). No statistically difference was found in the IL-4 level
      between the two groups. Linear regression analysis manifested significant
      interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4
      (r = 0.57, P = 0.021), IFN-gamma/IL-4 ratio (r = 0.42, P = 0.028) in the IDC
      group. While no correlation was found for AA, AG genotype and the A allele
      frequency. CONCLUSION: CTLA-4 gene exon 1 A49-->G substitution is associated with
      an increased IDC genetic susceptibility, which implicates that the CTLA-4 gene
      may have a significant role in IDC, possibly via a Thr-->Ala change in CTLA-4
      signal peptide, with a result of functional change of sCTLA-4. The bias of
      Th1/Th2 paradigm is associated with the increased sCTLA-4 level under certain
      background of immunogenicity.

PMID- 16405854
TI  - Copper regulated synthesis, secretion and degradation of ceruloplasmin in a mouse
      immortalized hepatocytic cell line.
AB  - Ceruloplasmin, a blue copper oxidase circulating in serum of all vertebrates, is
      a glycoprotein synthesized mainly in hepatocytes and secreted into plasma with
      six tightly bound atoms of copper per molecule. Many aspects of the mechanisms by
      which synthesis and secretion of this protein are regulated by copper are still
      not known. In HepG2 hepatocarcinoma cells this fine regulation is not maintained;
      we have then utilized Met-murine-hepatocytes (MMH), isolated from the liver of
      transgenic mice expressing a truncated form of c-Met (hepatocyte growth factor
      receptor), that are immortalized but not transformed. Copper deficiency was
      induced by treatment of cells with bathocuproine disulphonate. Experiments of
      metabolic labeling with 35S-methionine-cysteine and of Western blotting followed
      by immunostaining, demonstrated that maturation and secretion of ceruloplasmin
      but not its synthesis are affected by copper availability. In this paper we have
      shown that in copper deficiency ceruloplasmin accumulates in a pre-Golgi
      compartment, in which the protein is still in a Endo H sensitive form, and where
      presumably copper binding to the apo-protein takes place. Moreover, we found that
      treatment of copper-deficient cells with the proteasomal inhibitor lactacycstin
      leads to immature ceruloplasmin accumulation in the cell. We have optimized
      conditions to induce in vitro copper deficiency and found that MMH-D3 cells
      represent a suitable model to study in detail the molecular mechanism of copper
      regulated ceruloplasmin synthesis, secretion and degradation.

PMID- 16405856
TI  - Spectrin and ubiquitination: a review.
AB  - This review covers the observations leading to the conclusion that erythrocyte
      spectrin is a chimeric E2/E3 ubiquitin conjugating/ligating enzyme and the impact
      of this activity on the cell. Spectrin is important for the shape and the
      physical properties of the red blood cell, such as deformability and resistance
      to mechanical stress. The involvement of RBC spectrin in the ubiquitination
      process has been demonstrated. Human erythrocyte alpha-spectrin can facilitate
      formation of ubiquitin-spectrin adducts and conjugates in cell free systems (28).
      Computer analysis revealed domains that contained significant homologies to known
      consensus catalytic E2 and E3 sequences, and allowed us to develop a model for
      alpha-spectrin ubiquitin conjugating enzyme (E2) and ubiquitin protein ligase
      (E3) enzymatic activities. The model has been tested and the precise E2/E3
      site(s) identified by site-specific mutational analyses using a GST-fusion alpha
      spectrin(2005-2415) recombinant in an in vitroubiquitination assay (26). The
      results indicated that cysteine 2071 and cysteine 2100 are critical for alpha
      spectrin(2005-2415) E2/E3 activity as expected. However, both Cys2071 and Cys2100
      are capable of transferring ubiquitin from an E1 enzyme to target sites within
      alpha-spectrin(2005-2415). This revealed a redundancy of function for human RBC
      spectrin's chimeric E2/E3 ubiquitin conjugating/ligating activity. Since spectrin
      is the major structural component of the erythrocyte membrane skeleton, and it
      constitutes 20% of the total RBC membrane protein, its ubiquitination enzymatic
      activity could play an important role in both erythropoietic cells and mature
      RBCs. This could also be one reason for evolving this redundancy of function.

PMID- 16405855
TI  - Regulation of organ development by the NKX-homeodomain factors: an NKX code.
AB  - Mammalian development is a highly coordinated process that involves sequential
      and time-dependent gene regulation. Deregulation of this process can have
      functional or morphological consequences, possibly causing lethality or organ
      dysfunction. Homeotic genes are considered the master regulators of early
      developmental processes. Of the many homeodomain genes, the NK2 class represents
      a family of phylogenetically ancient proteins. NK2 homeobox family members are
      tissue-specific transcription factors distinguished by a common DNA binding
      structure unique among the homeodomain genes. Increasing evidence indicates that
      individual Nkx factors are critical regulators of whole organ development. In the
      sections below, we review the structure, regulation, and expression of the NK2
      gene family beginning with their discovery in Drosophila and relating the known
      features of vertebrate counterparts to the Drosophilaproteins. In particular, we
      note that each of the vertebrate NK2 proteins are associated with particular
      genetic anomalies leading to a variety of described disease states. Further,
      based upon our examination we propose a new paradigm of development based upon
      the regulatory capacity of the NK2 homeodomain proteins termed the "Nkx Code"

PMID- 16405857
TI  - Understanding the effect of deployment on the risk of fatal motor vehicle
      crashes: a nested case-control study of fatalities in Gulf War era veterans, 1991
      1995.
AB  - Motor vehicle crashes (MVCs) are an important cause of morbidity and premature
      loss of life among military personnel during peacetime and particularly following
      combat. A nested case-control study of fatal MVC occurring between 1991 and 1995
      was conducted in a cohort of Gulf War era veterans. Cases were validated MVC
      deaths in the Fatality Analysis Reporting System. Controls were selected using
      risk set sampling by gender and year of case ascertainment in a 10:1 ratio.
      Preliminary results, consistent with previous reports of increased fatal MVC risk
      among returning combat veterans, showed a crude odds ratio of 1.45 (95%
      confidence interval 1.27-1.65). Multivariable logistic regression modeling was
      used to identify important independent predictors, as well as to quantify the
      influence of deployment on a risk profile for fatal MVC. Because of significant
      interaction between deployment and inpatient diagnosis of substance abuse, the
      final model was stratified by deployment status. Results suggest that
      demographic, military, and behavioral characteristics of deployed healthy
      warriors are similar to the risk profile for fatal MVC. In addition to young,
      single, high school-educated, enlisted male personnel, those who served during
      times of ground combat, particularly in infantry, gun crews, or seamanship
      occupations, should be targeted for preventive interventions.

PMID- 16405858
TI  - Crash involvement of drivers with multiple crashes.
AB  - A goal for any licensing agency is the ability to identify high-risk drivers.
      Kentucky data show that a significant number of drivers are repeatedly involved
      in crashes. The objective of this study is the development of a crash prediction
      model that can be used to estimate the likelihood of a driver being at fault for
      a near future crash occurrence. Multiple logistic regression techniques were
      employed using the available data for the Kentucky licensed drivers. This study
      considers as crash predictors the driver's total number of previous crashes,
      citations accumulated, the time gap between the latest two crashes, crash type,
      and demographic factors. The driver's total number of previous crashes was
      further disaggregated into the drivers' total number of previous at-fault and not
      at-fault crashes. The model can be used to correctly classify at-fault drivers up
      to 74.56% with an overall efficiency of 63.34%. The total number of previous at
      fault crash involvements, and having previous driver license suspensions and
      traffic school referrals are strongly associated with a driver being responsible
      for a subsequent crash. In addition, a driver's likelihood to be at fault in a
      crash is higher for very young or very old, males, drivers with both speeding and
      non-speeding citations, and drivers that had a recent crash involvement. Thus,
      the model presented here enables agencies to more actively monitor the likelihood
      of a driver to be at fault in a crash.

PMID- 16405859
TI  - An application of Stafford and Warr's reconceptualisation of deterrence to a
      group of recidivist drink drivers.
AB  - Recent revisions of deterrence theory have highlighted the powerful effects of
      personal and vicarious punishment avoidance on criminal activity. The present
      paper reports on an application of Stafford and Warr's [Stafford, M.C., Warr, M.,
      1993. A reconceptualization of general and specific deterrence. J. Res. Crime
      Delinq. 30 (2), 123-135] reconceptualisation of deterrence theory to a group of
      recidivist drink drivers to explain their self-reported offending behaviours. The
      analysis indicated that punishment avoidance exerted the greatest influence on
      self-reported offending behaviours, although perceptions of arrest certainty and
      severity also appear associated with drink driving offences. In contrast,
      vicarious exposure to others who have been punished or avoided punishment was not
      associated with further drink driving behaviours. The results suggest that
      recidivist drink drivers are not heavily influenced by vicarious experiences, and
      that past behaviour is an efficient predictor of future behaviour. The findings
      have direct implications for the reconceptualisation and application of
      deterrence models to elucidate offending behaviours.

PMID- 16405861
TI  - Thermodynamic properties of damaged DNA and its recognition by xeroderma
      pigmentosum group A protein and replication protein A.
AB  - The effects of the lesions induced by single, site-specific 1,2-GG or 1,3-GTG
      intrastrand adducts of cis-diamminedichloroplatinum(II) formed in
      oligodeoxyribonucleotide duplexes on energetics of DNA were examined by means of
      differential scanning calorimetry. These effects were correlated with affinity of
      these duplexes for damaged-DNA binding-proteins XPA and RPA; this affinity was
      examined by gel electrophoresis. The results confirm that rigid DNA bending is
      the specific determinant responsible for high-affinity interactions of XPA with
      damaged DNA, but that an additional important factor, which affects affinity of
      XPA to damaged DNA, is a change of thermodynamic stability of DNA induced by the
      damage. In addition, the results also confirm that RPA preferentially binds to
      DNA distorted so that hydrogen bonds between complementary bases are interrupted.
      RPA also binds to non-denaturational distortions in double-helical DNA, but
      affinity of RPA to these distortions is insensitive to alterations of
      thermodynamic stability of damaged DNA.

PMID- 16405860
TI  - Expression of enzymatically active human granzyme 3 in Escherichia coli for
      analysis of its substrate specificity.
AB  - Human granzyme 3 (Gr3) is a serine protease contained in the granules of natural
      killer cells and cytotoxic T lymphocytes. To elucidate the biochemical and
      physiological characteristics of Gr3, we attempted to prepare an enzymatically
      active recombinant human Gr3 without refolding and proteolytic activation. An
      expression vector was constructed, in which the pre-/pro-peptide coding sequence
      of Gr3 was replaced with the bacterial pelB leader sequence. The resultant
      expression product was a fully active protease in the periplasmic fraction of
      Escherichia coli and was purified to homogeneity. The purified enzyme effectively
      hydrolyzed Z-Lys-SBzl, a conventionally used substrate of Gr3. In addition, it
      also hydrolyzed the peptide substrate library FRETS-25Xaa series, required basic
      amino acid residues, Arg or Lys, at the P1 position, and most efficiently
      hydrolyzed the carboxylic side of Phe-Tyr-Arg downward arrow (P3-P2-P1) sequence
      of the 475 tripeptide combinations.

PMID- 16405862
TI  - Heterogeneous activation of the medial pterygoid muscle during simulated
      clenching.
AB  - The aim of this study was to investigate whether the medial pterygoid muscle
      shows differential activation under experimental conditions simulating force
      generation during jaw clenching. To answer this question, the electromyographic
      activity of the right medial pterygoid was recorded with two intramuscular
      electrodes placed in an anterior and posterior muscle region, respectively.
      Intraoral force transfer and force measurement were achieved by a central bearing
      pin device equipped with strain gauges. The activity distribution in the muscle
      was recorded in a central mandibular position during generation of eight
      different force vectors at a constant amount of force (F=150 N). The investigated
      muscle regions showed different amounts of EMG activity. The relative intensity
      of the activation in the two regions changed depending on the task. In other
      words, the muscle regions demonstrated heterogeneous changes of the EMG pattern
      for various motor tasks. The results indicate a heterogeneous activation of the
      medial pterygoid muscle under test conditions simulating force generation during
      clenching. This muscle behaviour might offer an explanatory model for the
      therapeutic effects of oral splints.

PMID- 16405864
TI  - Structures of pulmonary surfactant films adsorbed to an air-liquid interface in
      vitro.
AB  - Phospholipid films can be preserved in vitro when adsorbed to a solidifiable
      hypophase. Suspensions of natural surfactant, lipid extract surfactants, and
      artificial surfactants were added to a sodium alginate solution and filled into a
      captive bubble surfactometer (CBS). Surfactant film was formed by adsorption to
      the bubble of the CBS for functional tests. There were no discernible differences
      in adsorption, film compressibility or minimal surface tension on quasi-static or
      dynamic compression for films formed in the presence or absence of alginate in
      the subphase of the bubble. The hypophase-film complex was solidified by adding
      calcium ions to the suspension with the alginate. The preparations were stained
      with osmium tetroxide and uranyl acetate for transmission electron microscopy.
      The most noteworthy findings are: (1) Surfactants do adsorb to the surface of the
      bubble and form osmiophilic lining layers. Pure DPPC films could not be
      visualized. (2) A distinct structure of a particular surfactant film depends on
      the composition and the concentration of surfactant in the bulk phase, and on
      whether or not the films are compressed after their formation. The films appear
      heterogeneous, and frequent vesicular and multi-lamellar film segments are seen
      associated with the interfacial films. These features are seen already upon film
      formation by adsorption, but multi-lamellar segments are more frequent after film
      compression. (3) The rate of film formation, its compressibility, and the minimum
      surface tension achieved on film compression appear to be related to the film
      structure formed on adsorption, which in turn is related to the concentration of
      the surfactant suspension from which the film is formed. The osmiophilic surface
      associated surfactant material seen is likely important for the surface
      properties and the mechanical stability of the surfactant film at the air-fluid
      interface.

PMID- 16405863
TI  - Detection of cleaved alpha-fodrin autoantigen in Sjogren's syndrome: apoptosis
      and co-localisation of cleaved alpha-fodrin with activated caspase-3 and cleaved
      poly(ADP-ribose) polymerase (PARP) in labial salivary glands.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disease which targets the
      exocrine glands and is associated with autoantibodies. The mechanism of salivary
      gland destruction or autoantibody production is poorly understood but it is
      increasingly accepted that apoptosis plays a role. OBJECTIVE: The objective of
      this study is to demonstrate the presence of cleaved alpha-fodrin autoantigen and
      apoptosis in the salivary glands of patients with primary Sjogren's syndrome.
      METHODS: 18 patients with primary Sjogren's syndrome provided tissues from a
      labial salivary gland biopsy. Using terminal deoxynucleotidyl transferase
      mediated dUTP nick end labelling (TUNEL) assays to detect DNA fragmentation
      followed by sequential immunoperoxidase assays in the same patient biopsy to
      detect cleaved alpha-fodrin, Poly(ADP-ribose) polymerase (PARP), and caspase-3,
      we show a co-localisation between apoptotic markers and disease. RESULTS: Co
      localisation of cleaved alpha-fodrin, PARP and caspase-3 expression was
      demonstrated primarily in the ducts along with DNA fragmentation in 16/18
      salivary gland biopsies from Sjogren's syndrome patients. None of these apoptotic
      markers was strongly expressed in healthy tissues. CONCLUSION: Apoptotic signals
      may provide useful therapeutic targets and cleaved alpha-fodrin may prove to be a
      marker of disease in primary Sjogren's syndrome. Further studies are required to
      ascertain the specific association of cleaved alpha-fodrin with primary and
      secondary Sjogren's syndrome.

PMID- 16405865
TI  - Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2
      protein.
AB  - Numerous studies have suggested that the NF2 protein merlin is involved in the
      regulation of abnormal cell growth and proliferation. In this study, to better
      understand the merlin's mechanisms that contribute to the inhibition of
      tumorigenesis, we examined the potential action of merlin on the cell
      proliferative signaling pathways in response to growth hormone (GH). Merlin
      effectively attenuated the GH-induced serum response element (SRE) and Elk-1
      mediated transcriptional activation, as well as the endogenous SRE-regulated gene
      c-fos expression in NIH3T3 cells. In addition, merlin prevented the Raf-1 complex
      activation process, which resulted in the suppression of MAP kinase/ERK,
      extracellular signal-regulated kinase (ERKs), and Elk-1 phosphorylation, which
      are the downstream signals of Raf-1. Moreover, it was shown that merlin
      interacted with endogenous growth factor receptor bound 2 (Grb2) protein and
      inhibited its expression. These results suggest that merlin contributes, via its
      protein-to-protein interaction with Grb2 and consequent inhibition of the MAPK
      pathways, to the regulation of the abnormal cell proliferation, and this provides
      a further mechanism underlying the tumor suppressor function of merlin.

PMID- 16405867
TI  - Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and
      suicidal behavior using systematic meta-analysis.
AB  - Serotonin 2A receptor (5-HT2A) gene was implicated to be associated with both
      schizophrenia and suicidal behavior due to its role of key neurotransmitter in
      many physiologic processes. Association studies were reported in different
      populations, however, a great number of subsequent studies have produced contrary
      results, possibly reflecting inadequate statistical power. With the cumulative
      data in recent years in both European and Asian populations, particularly in
      Asian populations, it was necessary to carry out a comprehensive analysis of
      previous findings. The meta-analysis, therefore, combined all English and Chinese
      studies using multiple research methods published up to July 2005 to give a new
      picture of the role of the 5-HT2A gene. Compared with significant results
      reported previously, the current large samples (73 studies in all) failed to find
      significant association of the T102C polymorphism with either schizophrenia or
      suicidal behavior. Evidence of significant association was only detected between
      A-1438G and suicidal behavior. The current study did not support the association
      of the 5-HT2A gene with either schizophrenia or suicidal behavior.

PMID- 16405866
TI  - Energy barriers, cooperativity, and hidden intermediates in the folding of small
      proteins.
AB  - Current theoretical views of the folding process of small proteins (<
      approximately 100 amino acids) postulate that the landscape of potential mean
      force (PMF) for the formation of the native state has a funnel shape and that the
      free energy barrier to folding arises from the chain configurational entropy
      only. However, recent theoretical studies on the formation of hydrophobic
      clusters with explicit water suggest that a barrier should exist on the PMF of
      folding, consistent with the fact that protein folding generally involves a large
      positive activation enthalpy at room temperature. In addition, high-resolution
      structural studies of the hidden partially unfolded intermediates have revealed
      the existence of non-native interactions, suggesting that the correction of the
      non-native interactions during folding should also lead to barriers on PMF. To
      explore the effect of a PMF barrier on the folding behavior of proteins, we
      modified Zwanzig's model for protein folding with an uphill landscape of PMF for
      the formation of transition states. We found that the modified model for short
      peptide segments can satisfy the thermodynamic and kinetic criteria for an
      apparently two-state folding. Since the Levinthal paradox can be solved by a
      stepwise folding of short peptide segments, a landscape of PMF with a locally
      uphill search for the transition state and cooperative stabilization of folding
      intermediates/native state is able to explain the available experimental results
      for small proteins. We speculate that the existence of cooperative hidden folding
      intermediates in small proteins could be the consequence of the highly specific
      structures of the native state, which are selected by evolution to perform
      specific functions and fold in a biologically meaningful time scale.

PMID- 16405869
TI  - Binding kinetics and duration of in vivo action of novel prolyl oligopeptidase
      inhibitors.
AB  - Prolyl oligopeptidase (POP) is a serine protease that specifically hydrolyses
      small peptides at the carboxyl end of the proline residue. POP has gained
      pharmaceutical interest, since its inhibitors have been shown to have antiamnesic
      properties in rat. We examined the effect of the 2(S)-substituents CN and
      COCH(2)OH at the P1 site of the parent inhibitors isophthalic acid 2(S)
      (cyclopentanecarbonyl)pyrrolidine-l-prolyl-pyrrolidine amide and 4-phenylbutanoyl
      l-prolyl-pyrrolidine and bulky 5-t-butyl group at the P2 site l-prolyl residue of
      the parent inhibitor 4-phenylbutanoyl-l-prolyl-pyrrolidine on the binding
      kinetics to the enzyme. In addition, we studied the duration of POP inhibition in
      the rat tissues in vivo after i.p. administration. CN and COCH(2)OH substituents
      at the P1 site pyrrolidine group were found to greatly increase the affinity of
      the inhibitor and the enzyme-inhibitor complex half-life. In addition, 5-t-butyl
      group at the P2 site l-prolyl residue increased the dissociation half-life of the
      enzyme-inhibitor complex, without much affecting the inhibitory potency. The
      duration of the inhibition in the rat tissues followed the inhibition kinetic
      properties in that the compounds with fast dissociation produced shorter
      inhibition in the rat tissues than the compounds with slow dissociation. The
      duration of POP inhibition of compounds was evidently not governed by their serum
      clearance. The fact that the in vivo pharmacodynamic behaviour of POP inhibitors
      can be predicted by their in vitro-properties may be of importance when designing
      therapeutically useful POP inhibitors.

PMID- 16405870
TI  - Differential modulation of thalamic neurons by optokinetic nuclei in the pigeon.
AB  - The visual system in the pigeon is composed of the tectofugal, thalamofugal and
      accessory optic pathways. Though their anatomy and physiology have been
      extensively studied, the functional interactions between these pathways are
      largely unknown. The present study shows by using multiple electrophysiological
      techniques that firing activity in the nucleus opticus principalis thalami (OPT)
      of the thalamofugal pathway is differentially modulated by the pretectal nucleus
      lentiformis mesencephali (nLM) and the nucleus of the basal optic root (nBOR) of
      the accessory optic system, two optokinetic nuclei responsible for generating eye
      movements to stabilize the image on the retina. Reversible inactivation,
      electrical stimulation, microiontophoresis and receptive field mapping
      experiments all consistently indicate that the nBOR-OPT pathway is inhibitory and
      mediated by GABA as a transmitter and its GABAA receptors, whereas the nLM-OPT
      pathway is excitatory and mediated by glutamate as a transmitter and its NMDA
      receptors. They also differentially modulate the size and/or responsiveness of
      receptive fields in OPT cells as well. Numerous electrode tip sites were
      histologically confirmed in the neural structures under study. The results
      suggest that these optokinetic nuclei may dually modulate the transfer of visual
      information from the retina to the telencephalon at the thalamic level during eye
      movements.

PMID- 16405871
TI  - Cortical adaptations and motor performance improvements associated with short
      term bimanual training.
AB  - Bimanual movement can increase activity within the stroke-affected hemisphere and
      may contribute to recovery in some patients. To understand how bimanual learning
      may aid recovery post-stroke, the present study used EEG to investigate cortical
      adaptations associated with short-term bimanual training and the behavioral
      modulations that transfer to unimanual movement in healthy individuals. Movement
      related potentials (MRP) and reaction times (RT) were recorded from 10 healthy
      subjects during blocks of unimanual visuomotor trials before and after a bimanual
      training task. We hypothesized that short-term bimanual practice would induce
      adaptive cortical changes evident in the MRPs to movements involving a single
      hand. Post-training results showed that: (1) the late MRP amplitude did not
      change, (2) RT significantly decreased, and (3) there was a trend for the early
      MRP amplitude to increase. There was a strong relationship between modulation of
      early MRP amplitude and RT in the unimanual movement blocks before and after
      training. Specifically, a subgroup showed a significant decrease in RT in
      conjunction with a significant increase in the early MRP amplitude. Lastly,
      comparing later to earlier trials within the bimanual training block, task
      accuracy and early MRP amplitude significantly increased and (2) a positive re
      afferent potential significantly decreased. Results suggest that short-term
      bimanual training is associated with possible transfer effects to a unimanual
      task reflected in changes of MRP components and RT. Furthermore, results from the
      bimanual training trial itself indicate that short-term bimanual training can
      change the level of motor preparation and sensory feedback in all subjects.

PMID- 16405868
TI  - Anti-Tat and anti-HIV activities of trimers of n-alkylglycines.
AB  - Transcription of human immunodeficiency virus (HIV-1) is activated by viral Tat
      protein which regulates HIV-LTR transcription and elongation. In the present
      report, the evaluation of the anti-Tat activity of a combinatorial library
      composed of 5120 N-trialkylglycines is reported. The antiviral activity was
      studied through luciferase-based assays targeting the HIV-1 promoter activation
      induced by the HIV-1 Tat protein. We identified five peptoids with specific anti
      HIV-1 Tat activity; none of these peptoids affected the binding of HIV-1 Tat
      protein to the viral TAR RNA. Using a recombinant-virus assay in which luciferase
      activity correlates with the rate of HIV-1 transcription we have detected that
      one of the five selected peptoids, NC37-37-15C, is a potent inhibitor of HIV-1
      LTR transcription in both primary T lymphocytes and transformed cell lines. The
      inhibitory effect of NC37-37-15C, which is additive with azidothymidine (AZT),
      correlates with its ability to inhibit CTD phosphorylation and shows a suitable
      profile for development of novel anti-HIV-1 drugs. Likewise, the structural
      simplicity of N-alkylglycine oligomers makes these peptidomimetics amenable to
      structural manipulation, thus facilitating the optimisation of lead molecules for
      drug-like properties.

PMID- 16405872
TI  - Neural processing of observed oro-facial movements reflects multiple action
      encoding strategies in the human brain.
AB  - In this experiment, the oscillatory responses of the MEG were characterized
      during the observation of four viewing conditions: (a) observation of mouth
      movements, (b) observation of a non-biological motion stimulus (a mechanical
      aperture opening and shutting), (c) observation of object-directed mouth
      movements and (d) observation of speech-like mouth movements. Data were analyzed
      using synthetic aperture magnetometry (SAM) in three frequency bands, beta (15-35
      Hz), gamma (35-70 Hz) and alpha/mu (8-15 Hz). Results showed that observations of
      biological motion resulted in beta desynchronization over lateral sensorimotor
      areas, while observations of non-biological motion resulted in a more medial
      desynchronization, an effect that may be related to the processing of a
      structured event sequence. Observation of linguistic movements resulted in less
      alpha/beta desynchronization in posterior brain regions in comparison to
      biological motion stimuli, suggesting that linguistically-relevant stimuli are
      processed with different neuronal systems than those recruited by normal action
      observation. We suggest that non-linguistic actions recruit dorsal systems while
      linguistic actions engage ventral processing systems. Object-directed movements
      showed the largest sensorimotor activations, suggesting that, as is the case for
      observations of hand movements, motoric processing is particularly sensitive to
      the viewing of goal-directed actions. Taken together, the results indicate that
      the brain utilizes multiple action encoding strategies, tailored to the function
      of the observed movement.

PMID- 16405873
TI  - Phospholipase Cbeta1 modulates pain sensitivity, opioid antinociception and
      opioid tolerance formation.
AB  - Phospholipase C (PLC) activity has been implicated in multiple opioid-induced
      sequelae. The relevance of PLC-linked pathways to opioid actions is isoform
      specific. Chronic morphine augments PLCbeta1 signaling while diminishing that of
      PLCbeta3. This suggests that PLCbeta1 makes an important contribution to opioid
      tolerance formation (PNAS 100: 13686-1369, 2003). In the present study, PLCbeta1
      knockout animals (-/-) were used to assess the relevance of PLCbeta1 to pain
      thresholds, morphine antinociception and analgesic tolerance formation. Response
      latencies to thermal nociceptive stimuli were markedly diminished in -/- animals
      relative to their wild-type (+/+) and heterozygous (+/-) counterparts; thermal
      nociceptive thresholds obtained in +/+ and +/- mice did not differ. This suggests
      that the contribution of PLCbeta1 to thermal pain thresholds requires a critical
      concentration of PLCbeta1 protein. PLCbeta1 genotype also influenced acute and
      chronic responsiveness to morphine. Analgesic dose responsiveness and the
      magnitude of analgesic tolerance formation to morphine were significantly
      attenuated in -/- vs. +/+ animals. Notably, in contrast to thermal nociceptive
      thresholds, acute and chronic morphine responsiveness differed significantly only
      between +/+ and -/- genotypes and not between -/- vs. +/- groups. These data
      suggest that whereas the contribution of PLCbeta1 to thermal nociceptive response
      thresholds requires a critical concentration of PLCbeta1 protein, its
      participation in morphine analgesic and tolerance-producing mechanisms is graded.
      Importantly, GTPgammaS binding studies revealed that there is no detectable
      diminution in functional opioid receptors in spinal tissue from -/- animals. This
      underscores the importance of PLCbeta1 to morphine sequelae that are initiated
      downstream from the opioid receptor.

PMID- 16405874
TI  - Identification and functional characterization of mouse TPO1 as a myelin membrane
      protein.
AB  - TPO1 is a member of the AIGP family, a unique group of proteins that contains 11
      putative transmembrane domains. Expression of the rat TPO1 gene is upregulated in
      cultured oligodendrocytes (OLs) during development from pro-oligodendroblasts to
      postmitotic OLs. However, the distribution of native TPO1 protein in cultured OLs
      and in the brain has not been elucidated. We investigated the distribution and
      cellular function of TPO1 in myelinating cells of the nervous system. In mice,
      TPO1 gene expression was detected in the central (CNS) and peripheral (PNS)
      nervous systems and was markedly upregulated at postnatal days 10-20, an early
      phase of myelination in the mouse brain. To investigate TPO1 localization, we
      generated affinity-purified antibodies to synthetic peptides derived from mouse
      TPO1. Immunohistochemical analysis showed that TPO1 was expressed in OLs and
      Schwann cells but not in neurons and astrocytes. Schwann cells from trembler
      mice, which lack PNS myelin, had significantly decreased TPO1 expression and an
      altered localization pattern, suggesting that TPO1 is a functional myelin
      membrane protein. In OL lineage cell cultures, TPO1 was detected in A2B5+ bipolar
      early progenitors, A2B5+ multipolar Pro-OLs, GalC+ immature OLs and MBP+ mature
      OLs. The subcellular localization of TPO1 in OL lineage cells was mapped to the
      GM130+ Golgi in cell bodies and Fyn+ cell processes and myelin-like sheets.
      Furthermore, TPO1 selectively colocalized with non-phosphorylated Fyn and
      promoted Fyn autophosphorylation in COS7 cells, suggesting that TPO1 may play a
      role in myelin formation via Fyn kinase activation in the PNS and CNS.

PMID- 16405875
TI  - Treatment with olanzapine increases cell proliferation in the subventricular zone
      and prefrontal cortex.
AB  - The present study examines the effect of chronic treatment with two atypical
      neuroleptics, commonly used to treat schizophrenia. Adult rats were given either
      risperidone or olanzapine in their drinking water for 21 days. Memory was
      assessed on the first and last day of treatment using an object discrimination
      test, and the rate of cell proliferation in the subventricular zone (SVZ),
      dentate gyrus (DG) and prefrontal cortex (PFC) was quantified by immuno staining
      for Ki-67. The results show that both risperidone and olanzapine significantly
      improved performance in object discrimination after 21 days, and additionally,
      olanzapine significantly increased cell proliferation in the SVZ and PFC but not
      the DG.

PMID- 16405876
TI  - Arrhythmogenesis after cell transplantation post-myocardial infarction. Four
      burning questions--and some answers.

PMID- 16405877
TI  - Structure and function of matrix metalloproteinases and TIMPs.
AB  - Matrix metalloproteinases (MMPs), also called matrixins, function in the
      extracellular environment of cells and degrade both matrix and non-matrix
      proteins. They play central roles in morphogenesis, wound healing, tissue repair
      and remodelling in response to injury, e.g. after myocardial infarction, and in
      progression of diseases such as atheroma, arthritis, cancer and chronic tissue
      ulcers. They are multi-domain proteins and their activities are regulated by
      tissue inhibitors of metalloproteinases (TIMPs). This review introduces the
      members of the MMP family and discusses their domain structure and function,
      proenyme activation, the mechanism of inhibition by TIMPs and their significance
      in physiology and pathology.

PMID- 16405879
TI  - Chemical synthesis and NMR characterization of structured polyunsaturated
      triacylglycerols.
AB  - The chemical synthesis of pure triacylglycerol (TAG) regioisomers, that contain
      long chain polyunsaturated fatty acids, such as arachidonic acid (AA) or
      docosahexaenoic acid (DHA), and saturated fatty acids, such as lauric acid (La)
      or palmitic acid (P), at defined positions, is described. A single step
      methodology using (benzotriazol-1-yloxy)-tripyrrolidinophosphonium
      hexafluorophosphate (PyBOP), an activator of carboxyl group commonly used in
      peptide synthesis and occasionally used in carboxylic acid esterification, has
      been developed for structured TAG synthesis. Identification of the fatty acyl
      chains for each TAG species was confirmed by atmospheric pressure chemical
      ionisation mass spectrometry (APCI-MS) and fatty acid positional distribution was
      determined by (1)H and (13)C NMR spectra. The generic described procedures can be
      applied to a large variety of substrates and was used for the production of
      specific triacylglycerols of defined molecular structures, with high
      regioisomeric purity. Combination of MS and NMR was shown to be an efficient tool
      for structural analysis of TAG. In particular, some NMR signals were demonstrated
      to be regioisomer specific, allowing rapid positional analysis of LC-PUFA
      containing TAG.

PMID- 16405878
TI  - Prednisone prevents atrial fibrillation promotion by atrial tachycardia
      remodeling in dogs.
AB  - BACKGROUND: There is evidence suggesting involvement of oxidative stress,
      inflammation, and calcineurin/nuclear factor of activated T cell pathways in
      atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and
      calcineurin-inhibitory drugs on promotion of atrial fibrillation by atrial
      tachycardia-induced remodeling in dogs. METHODS AND RESULTS: Dogs were subjected
      to atrial tachypacing at 400 bpm in the absence and presence of treatment with
      prednisone (15 or 50 mg/day) or ibuprofen (anti-inflammatory) or cyclosporine-A
      (calcineurin inhibitor). Serial closed-chest electrophysiological studies were
      performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. A
      final open-chest study was performed on day 8. Serum C-reactive protein was
      measured by ELISA and nitric oxide synthase by Western blotting. The mean
      duration of induced atrial fibrillation was markedly increased by tachypacing
      alone, from 26+/-8 to 962+/-317 s (p<0.01), and the atrial effective refractory
      period was decreased from 117+/-4 to 73+/-7 ms (p<0.001; cycle-length 300 ms).
      Tachypacing-induced effective refractory period shortening and atrial
      fibrillation promotion were unaffected by ibuprofen or cyclosporine-A; however,
      both doses of prednisone suppressed tachypacing-remodeling effects (atrial
      fibrillation duration to 96+/-60 s and 28+/-11 s at higher and lower doses,
      respectively; effective refractory period to 101+/-6 ms for higher-dose and 105+/
      3 ms for lower-dose group). In addition, prednisone (but not ibuprofen or
      cyclosporine) significantly decreased C-reactive protein concentrations and
      attenuated the increase in endothelial nitric oxide synthase expression caused by
      atrial tachypacing. CONCLUSIONS: Prednisone prevents the electrophysiological and
      atrial fibrillation-promoting effects of atrial tachycardia-remodeling, possibly
      by an anti-inflammatory action, whereas the less potent anti-inflammatory
      ibuprofen and the calcineurin inhibitor cyclosporine-A are without effect.

PMID- 16405880
TI  - Incorporation of PEG-lipids in arsonoliposomes results in formation of highly
      stable arsenic-containing vesicles.
AB  - We investigated the effect of pegylation on the physical stability, morphology
      and membrane integrity of arsonoliposomes. Arsonoliposomes composed of
      distearoylglycerophosphocholine (DSPC), cholesterol (Chol) and the palmitoyl side
      chain arsonolipid (with concentrations ranging from 0 mol% [DSPC/Chol vesicles]
      to 53 mol% of total lipid) containing either 4 or 8 mol% DPPE-PEG2000 or DSPE
      PEG2000, were prepared by sonication. Arsonoliposome membrane integrity was
      evaluated by measuring the retention of encapsulated calcein in vesicles (during
      incubation in buffer or fetal calf serum [FCS]) while physical stability was
      evaluated by measuring vesicle dispersion turbidity (during incubation in water
      or CaCl(2)). Vesicle morphology was studied by cryo-electron microscopy.
      Experimental results show that: (i) PEG-lipids are incorporated in
      arsonoliposomes (as confirmed by the vesicle zeta potential modulation), (ii)
      pegylation of arsonoliposomes prevents their aggregation and fusion in the
      presence of calcium ions and (iii) when 8 mol% of PEG-DSPE is incorporated in
      arsonoliposomes based on their arsonolipid content, two groups of pegylated
      vesicles are formed: low content arsonoliposomes (<20 mol% arsonolipid) which are
      highly leaky and high content arsonoliposomes (>27 mol% arsonolipid) which are
      highly stable (70% calcein retention after 24h incubation in fetal calf serum
      [FCS]). In addition to high membrane integrity, the high content pegylated
      arsonoliposomes are morphologically perfect round-shaped vesicles without the
      sharp edges typically observed with non-pegylated DSPC-containing
      arsonoliposomes.

PMID- 16405882
TI  - Population distribution of high sensitivity C-reactive protein values in
      Aboriginal Australians: a comparison with other populations.
AB  - OBJECTIVES: To examine the distribution of C-reactive protein (CRP) values in
      Aboriginal Australians and its relation to age and gender. METHODS: High
      sensitivity CRP levels were measured in 954 Aboriginal participants aged 5-74
      years. Fractional polynomial regressions were used to explore the relationship
      between CRP and age. RESULTS: CRP values changed with age and reached its lowest
      level around 10 years and then increased with age. Geometric means of CRP were
      7.3 (95% confidence interval (CI): 6.6, 8.1) and 4.1 (95% CI: 3.7, 4.6) for
      female and male adults, respectively. Adjusting for age, the ratio of female to
      male CRP concentrations was 1.67 (95% CI: 1.45, 1.99) for adults, and 1.09 (95%
      CI: 0.84, 1.42) for children 5 to 19 years. CONCLUSIONS: CRP changes with age.
      Females have higher CRP values than males. CRP values in Aboriginal people are
      substantially higher than other populations.

PMID- 16405881
TI  - Alterations of N-glycan branching and expression of sialic acid on amniotic fluid
      alpha-1-acid glycoprotein derived from second and third trimesters of normal and
      prolonged pregnancies.
AB  - BACKGROUND: Alterations in the AGP glycoform pattern are not only disease
      related, but also can occur during physiological processes such as pregnancy. In
      this paper, possible changes in human amniotic fluid AGP glycan branching and in
      the type of sialic acid glycosidic attachment to glycans were analyzed with
      regard to different stages of human pregnancy. METHODS: Crossed-affinity
      immunoelectrophoresis with concanavalin A was used to study AGP branching and
      lectin-ELISA with two agglutinins from Maackia amurensis and Sambucus nigra was
      applied to differentiate alpha2,3 and alpha2,6 type sialic acid attachments.
      RESULTS: Despite almost unchanged levels of total amniotic fluid AGP during
      pregnancy, alterations in N-glycan branching and in the expression of sialic acid
      linkage on AGP were found to be associated with different stages of normal
      pregnancy. Amniotic fluid AGP glycans derived from third trimester compared with
      those from the second trimester had a higher percentage of tri- and tetra
      antennary sialylated N-glycans. In the second trimester, sialic acid alpha2,6
      linkage occurred twice as frequently as alpha2,3 linkage, while during the third
      trimester alpha2,3 linkage increased and both types of linkage appeared in equal
      proportion. CONCLUSIONS: Branched and alpha2,3-sialylated AGP glycoforms in
      amniotic fluid could contribute to natural innate fetomaternal defense.

PMID- 16405883
TI  - Establishment of animal-vegetal polarity during maturation in ascidian oocytes.
AB  - Mature ascidian oocytes are arrested in metaphase of meiosis I (Met I) and
      display a pronounced animal-vegetal polarity: a small meiotic spindle lies
      beneath the animal pole, and two adjacent cortical and subcortical domains
      respectively rich in cortical endoplasmic reticulum and postplasmic/PEM RNAs
      (cER/mRNA domain) and mitochondria (myoplasm domain) line the equatorial and
      vegetal regions. Symmetry-breaking events triggered by the fertilizing sperm
      remodel this primary animal-vegetal (a-v) axis to establish the embryonic (D-V, A
      P) axes. To understand how this radial a-v polarity of eggs is established, we
      have analyzed the distribution of mitochondria, mRNAs, microtubules and
      chromosomes in pre-vitellogenic, vitellogenic and post-vitellogenic Germinal
      Vesicle (GV) stage oocytes and in spontaneously maturing oocytes of the ascidian
      Ciona intestinalis. We show that myoplasm and postplasmic/PEM RNAs move into the
      oocyte periphery at the end of oogenesis and that polarization along the a-v axis
      occurs after maturation in several steps which take 3-4 h to be completed. First,
      the Germinal Vesicle breaks down, and a meiotic spindle forms in the center of
      the oocyte. Second, the meiotic spindle moves in an apparently random direction
      towards the cortex. Third, when the microtubular spindle and chromosomes arrive
      and rotate in the cortex (defining the animal pole), the subcortical myoplasm
      domain and cortical postplasmic/PEM RNAs are excluded from the animal pole
      region, thus concentrating in the vegetal hemisphere. The actin cytoskeleton is
      required for migration of the spindle and subsequent polarization, whereas these
      events occur normally in the absence of microtubules. Our observations set the
      stage for understanding the mechanisms governing primary axis establishment and
      meiotic maturation in ascidians.

PMID- 16405884
TI  - Cooperative non-cell and cell autonomous regulation of Nodal gene expression and
      signaling by Lefty/Antivin and Brachyury in Xenopus.
AB  - Dynamic spatiotemporal expression of the nodal gene and its orthologs is involved
      in the dose-dependent induction and patterning of mesendoderm during early
      vertebrate embryogenesis. We report loss-of-function studies that define a high
      degree of synergistic negative regulation on the Xenopus nodal-related genes
      (Xnrs) by extracellular Xenopus antivin/lefty (Xatv/Xlefty)-mediated functional
      antagonism and Brachyury-mediated transcriptional suppression. A strong knockdown
      of Xlefty/Xatv function was achieved by mixing translation- and splicing-blocking
      morpholino oligonucleotides that target both the A and B alloalleles of Xatv.
      Secreted and cell-autonomous inhibitors of Xnr signaling were used to provide
      evidence that Xnr-mediated induction was inherently long-range in this situation
      in the large amphibian embryo, essentially being capable of spreading over the
      entire animal hemisphere. There was a greater expansion of the Organizer and
      mesendoderm tissues associated with dorsal specification than noted in previous
      Xatv knockdown experiments in Xenopus, with consequent exogastrulation and long
      term maintenance of expanded axial tissues. Xatv deficiency caused a modest
      animal-ward expansion of the marginal zone expression territory of the Xnr1 and
      Xnr2 genes. In contrast, introducing inhibitory Xbra-En(R) fusion constructs into
      Xatv-deficient embryos caused a much larger increase in the level and spatial
      extent of Xnr expression. However, in both cases (Xatv/Xlefty-deficiency alone,
      or combined with Xbra interference), Xnr2 expression was constrained to the
      superficial cell layer, suggesting a fundamental tissue-specific competence in
      the ability to express Xnrs, an observation with direct implications regarding
      the induction of endodermal vs. mesodermal fates. Our experiments reveal a two
      level suppressive mechanism for restricting the level, range, and duration of Xnr
      signaling via extracellular inhibition by Xatv/Xlefty coupled with potent
      indirect transcriptional repression by Xbra.

PMID- 16405885
TI  - Oral administration of the NADPH-oxidase inhibitor apocynin partially restores
      diminished cartilage proteoglycan synthesis and reduces inflammation in mice.
AB  - Apocynin, an inhibitor of NADPH-oxidase, is known to partially reverse the
      inflammation-mediated cartilage proteoglycan synthesis in chondrocytes. More
      recently, it was reported that apocynin prevents cyclooxygenase (COX)-2
      expression in monocytes. The present study aimed to investigate whether these in
      vitro features of apocynin could be confirmed in vivo. In a mouse model of
      zymosan-induced acute arthritis apocynin was administered orally (0, 3.2, 16 and
      80 microg/ml in the drinking water) and the effects on cartilage proteoglycan
      synthesis were monitored. In a mouse model of zymosan-induced inflammation of the
      ears apocynin was administered orally (14 mg/kg/day by gavage) and the effects on
      ear swelling and ex vivo produced prostaglandin E2 (PGE2) by lipopolysaccharide
      (LPS)-stimulated blood cells were measured. In this study, ibuprofen was used as
      a positive control (50 mg/kg/day by gavage) and animals received vehicle as a
      negative control. Apocynin dose-dependently reversed the inhibition of
      proteoglycan synthesis in articular cartilage of the arthritic joint. A
      statistically significant increase in proteoglycan synthesis was found at a dose
      of 80 microg/ml apocynin. Apocynin did not affect the proteoglycan synthesis of
      the control knee joints. Apocynin significantly decreased the zymosan-induced ear
      swelling at 1, 2 and 4 h (hours) after zymosan injection versus the vehicle
      treated group at 14 mg/kg/day. The ex vivo production of PGE2 by LPS-stimulated
      blood cells was significantly decreased after in vivo apocynin treatment.
      Ibuprofen decreased ear swelling at the same time-points as apocynin and
      inhibited the ex vivo produced PGE2. In conclusion, the present study confirmed
      two important features of apocynin in vivo: (1) oral administration of apocynin
      can partially reverse the inflammation-induced inhibition of cartilage
      proteoglycan synthesis, and (2) oral administration of apocynin has COX
      inhibitory effects similar to the non-steroidal anti-inflammatory drug (NSAID)
      ibuprofen. Therefore, apocynin might be of potential use during the treatment of
      chronic inflammatory joint diseases like osteoarthritis or rheumatoid arthritis.

PMID- 16405886
TI  - mu-Opioid influence on transmesothelial resistance of isolated sheep pleura and
      parietal pericardium.
AB  - The effect of morphine (mu-opioid receptor agonist) on the transmesothelial
      resistance (R(TM)) of sheep's pleura and parietal pericardium was studied using
      the Ussing chamber technique. Basal transmesothelial resistance of parietal
      pleura was found to be 19.57+/-0.32 Omega cm2 and of visceral pleura was found to
      be 19.41+/-0.31 Omega cm2, whereas that of parietal pericardium was found to be
      22.83+/-0.4 Omega cm2. Immediately after the addition of morphine (10(-9) M) both
      apically and basolaterally on the parietal pleura and parietal pericardium, these
      values were significantly increased (P<0.05). On the contrary, addition of
      morphine (10(-9) M) resulted in a rapid increase, only when placed basolaterally
      on the visceral pleura (P<0.05). In conclusion, our findings suggest that
      morphine, probably through mu-opioid stimulation, increases in vitro the
      transmesothelial resistance of the parietal pleura, of the visceral pleura when
      added basolaterally and of the parietal pericardium.

PMID- 16405887
TI  - Epithelial muscarinic M1 receptors contribute to carbachol-induced ion secretion
      in mouse colon.
AB  - Cholinergically induced intestinal anion secretion is generally believed to be
      caused by stimulation of epithelial muscarinic M3 receptors, whereas muscarinic
      M1 receptors are thought to be localized primarily on enteric neurons. In order
      to test this assumption, carbachol-stimulated Cl- secretion across distal colon,
      measured as increase in short-circuit current (I(sc)), was compared between M1
      knockout (M1R-KO) and M3-knockout (M3R-KO) mice. Surprisingly, the maximal
      increase in I(sc) evoked by carbachol was more than twice as large in M3R-KO
      compared to M1R-KO mice. This difference was not due to a reduced secretory
      capacity of the epithelium from M3R-KO animals, as forskolin stimulated a similar
      maximal I(sc) in both types of animals. The neurotoxin tetrodotoxin diminished,
      but did not abolish the secretory response evoked by carbachol in M3R-KO distal
      colon, suggesting the existence of epithelial muscarinic receptors other than the
      type M3. Furthermore, in muscarinic receptor wild-type animals, the muscarinic M1
      receptor antagonist pirenzepine inhibited the carbachol-stimulated I(sc) by more
      than 70% suggesting the presence of epithelial muscarinic M1 receptors; a
      conclusion, which was confirmed by the identification of mRNA for muscarinic M1
      receptors in isolated crypts from wild-type colon. Consequently, epithelial
      muscarinic receptors from the type M1 contribute to cholinergically induced ion
      secretion in mouse colon.

PMID- 16405888
TI  - Threonine 788 in integrin subunit beta1 regulates integrin activation.
AB  - In the present study, the functional role of suggested phosphorylation of the
      conserved threonines in the cytoplasmic domain of integrin subunit beta1 was
      investigated. Mutants mimicking phosphorylated and unphosphorylated forms of
      beta1 were expressed in beta1 deficient GD25 cells. T788 in beta1 was identified
      as a site with major influence on integrin function. The mutation to A788
      strongly reduced beta1-dependent cell attachment and exposure of the
      extracellular 9EG7 epitope, whereas replacement of T789 with alanine did not
      interfere with the ligand-binding ability. Talin has been shown to mediate
      integrin activation, but the talin head domain bound equally well to the wild
      type beta1 and the mutants indicating that the T788A mutation caused defect
      integrin activation by another mechanism. The phosphorylation-mimicking mutation
      T788D was fully active in promoting cell adhesion. GD25 cells expressing
      beta1T788D accumulated increased number of focal contacts and migrated slowly
      compared to GD25 beta1 wild-type. An analogous phenotype is seen when focal
      adhesion kinase activation is abrogated. However, neither the beta1T788D nor the
      beta1T788A mutation failed to induce tyrosine phosphorylation of focal adhesion
      kinase. The results suggest that phosphorylation of T788 in integrin beta1
      promotes inside-out receptor activation, as well as focal contact accumulation.

PMID- 16405889
TI  - Infusion of human umbilical cord blood cells protect against cerebral ischemia
      and damage during heatstroke in the rat.
AB  - Intravenously delivered human umbilical cord blood cells (HUCBC) have been
      previously shown to improve both morphologic and functional recovery of heat
      stroked rats. To extend these findings, we examined both the morphologic and
      functional alterations in the presence of HUCBC or human peripheral mononuclear
      cells (PBMC) 24 h before initiation of heatstroke. Anesthetized rats, 1 day
      before the initiation of heatstroke, were divided into three major groups and
      given the following: (a) serum-free lymphocyte medium (0.3 ml) intravenously; (b)
      PBMC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium); or (c) HUCBC (5 x 10(6)
      in 0.3 ml serum-free lymphocyte medium). Another group of rats were exposed to
      room temperature (26 degrees C) and used as normothermic controls. In vehicle
      treated heatstroke rats, their mean arterial pressure, cerebral blood flow, and
      brain PO(2) were all lower than in normothermic controls after the onset of
      heatstroke. However, their body temperatures and striatal levels of inducible
      nitric oxide synthase (iNOS)-dependent NO, ischemia and damage markers (e.g.,
      glycerol, glutamate, and lactate/pyruvate ratio), and neuronal damage in the
      striatum were all greater. The heatstroke-induced arterial hypotension, cerebral
      ischemia and hypoxia, and increased levels of iNOS-dependent NO in the striatum
      were all significantly reduced by pretreatment with HUCBC, but not with PBMC.
      Moreover, HUCBC were localized by immunohistochemistry and PCR analysis in the
      injured brain structures and spleen. These findings indicate that HUCBC
      transplantation, in addition to having therapeutic values, can be a good choice
      for preventing heatstroke occurrence.

PMID- 16405890
TI  - Hormonal regulation of the epithelial Na+ channel: from amphibians to mammals.
AB  - High-resistance epithelia derived from amphibian sources such as frog skin, toad
      urinary bladder, and the A6 Xenopus laevis kidney cell line have been widely used
      to elucidate the underlying mechanisms involved in the regulation of vectorial
      ion transport. More recently, the isolation of high-resistance mammalian cell
      lines has provided model systems in which to study differences and similarities
      between the regulation of ion transporter function in amphibian and mammalian
      renal epithelia. In the present study, we have compared the natriferic (Na+
      retaining) responses to aldosterone, insulin, and vasotocin/vasopressin in the A6
      and mpkCCDcl4 (mouse principal cells of the kidney cortical collecting duct) cell
      lines. The functional responses of the epithelial Na+ channel (ENaC) to hormonal
      stimulation were remarkably similar in both the amphibian and mammalian lines. In
      addition, insulin- and aldosterone-stimulated, reabsorptive Na+ transport in both
      cell lines requires the presence of functional PI3-kinase.

PMID- 16405891
TI  - Endometrial thickness in asymptomatic postmenopausal Nigerian women with and
      without hypertension.

PMID- 16405892
TI  - Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase
      are markers of inflammation and oxidative stress independent of the metabolic
      syndrome.
AB  - The present study attempted to establish whether elevated serum levels of alanine
      aminotransferase (ALT) and gamma glutamyltransferase (GGT) are independent (of
      each other) markers of systemic inflammation and oxidative stress as assessed by
      the plasma levels of C-reactive protein (CRP) and lipid peroxides (lipOX),
      regardless of the presence of underlying metabolic syndrome (as defined by the
      modified Adult Treatment Panel III (ATPIII) criteria). The plasma levels of CRP
      and lipOX were determined in 1483 middle-age Japanese men (42+/-9 years). A
      general linear model analysis indicated that elevated serum ALT and/or serum GGT
      (levels in the respective highest quartiles) were significantly related to the
      logarithms of the plasma levels of CRP (Beta=0.08 (0.05-0.11) and 0.08 (0.05
      0.11), respectively) and the logarithm of the plasma levels of lipOX (Beta=0.03
      (0.01-0.05) and 0.03 (0.01-0.05), respectively), regardless of the presence of
      underlying metabolic syndrome (MetS) (p<0.01). In addition, the presence of MetS
      and elevated serum levels of both of these liver enzymes additively increased the
      plasma levels of CRP and lipOX. Thus, it is proposed that elevated serum ALT and
      elevated serum GGT are independent markers of the activation of systemic
      inflammation and increased oxidative stress, independent of their relationship to
      MetS, and that the presence of MetS and elevations of both of these liver enzymes
      may additively worsen the atherogenic state.

PMID- 16405893
TI  - Type I and type III collagen synthesis and composition in the valve matrix in
      aortic valve stenosis.
AB  - Changes in the collagenous matrix may contribute to the pathogenesis and
      progression of human aortic valve stenosis (AS). To evaluate the significance of
      collagen I and III in the pathogenesis of AS, we studied their synthesis in
      diseased valves. Type I and type III collagen mRNA expression and the
      immunohistochemical localization of the collagen antigens were studied from 36 AS
      and 2 normal aortic valves. The concentrations of propeptides and telopeptide
      structure of type I (PINP, PICP, and ICTP) and those of III collagens (PIIINP and
      IIINTP) were measured by radioimmunoassays in soluble tissue extracts and trypsin
      solubilized calcified and non-calcified matrices of 11 AS and 24 healthy aortic
      valves of different ages. The synthesis of type I collagen, localized in the
      myofibroblasts adjacent to calcified nodules, was two- to three-fold in the AS
      samples compared to the controls. The proportion of collagen in the total protein
      fraction was 90% in the healthy valves, 50% in the non-calcified matrix, and 10%
      in the calcified matrix of AS valves. In the calcified valves, the ICTP content
      was six-fold compared to the age-matched controls and two-fold compared to the
      young control group. In the controls, the amount of ICTP in type I collagen
      decreased with age (r=-0.908, p<0.001) and was replaced by other cross-linked C
      telopeptide structure. The concentration of type III collagen decreased during
      aging (r=-0.753, p<0.001). The decrease in total collagen content, despite the
      increase in type I collagen synthesis indicates an increase in collagen turnover
      in AS. The calcification of the aortic valves is accompanied by increased amount
      of ICTP in type I collagen.

PMID- 16405894
TI  - ATP depletion in macrophages in the core of advanced rabbit atherosclerotic
      plaques in vivo.
AB  - The cores of rabbit plaques in vivo are hypoxic, suggesting that ATP depletion
      due to an insufficient supply of oxygen and nutrients could contribute to
      macrophage death in atherosclerotic plaques. During hypoxia, however, macrophages
      maintain ATP levels by anaerobic glycolysis. To directly assess ATP and glucose
      metabolites in plaques in vivo, we used bioluminescence imaging to map the
      concentrations of ATP, glucose, glycogen, and lactate in normal and
      atherosclerotic rabbit aortas in vivo. Hypoxia was assessed with NITP (7-(4'-(2
      nitroimidazol-1-yl)-butyl)-theophylline). Normal aortas and plaques <500 microm
      thick were not hypoxic and had homogenous concentrations of energy metabolites.
      In plaques >500 microm thick, however, the cores were characterized by ATP
      depletion, low concentrations of glucose and glycogen, and a high concentration
      of lactate. A majority of ATP-depleted macrophages within the core were viable
      but severely hypoxic and glucose depleted. Hyperoxia in vitro reversed the ATP
      depletion in macrophages in viable areas of the core. Our findings suggest that
      ATP depletion contributes to the death of macrophages in atherosclerotic lesions
      and to the formation of a necrotic core.

PMID- 16405895
TI  - Plasma interleukin (IL)-18 concentrations is elevated in patients with previous
      myocardial infarction and related to severity of coronary atherosclerosis
      independently of C-reactive protein and IL-6.
AB  - AIM: Interleukin-18 (IL-18) is a pro-inflammatory cytokine with a central role in
      the inflammatory cascade. In the present study, we investigated whether patients
      with precocious myocardial infarction have higher plasma IL-18 concentrations
      than matched controls. Furthermore, the relationships between plasma IL-18
      concentrations and coronary atherosclerosis, C-reactive protein (CRP),
      interleukin-6 (IL-6) and traditional cardiovascular risk factors were examined.
      METHODS AND RESULTS: Three hundred eighty-seven unselected survivors of a first
      myocardial infarction aged less than 60 years and 387 sex and age matched
      controls were enrolled in the study. A subset of patients (n=236) was evaluated
      by quantitative coronary angiography. Postinfarction patients had significantly
      higher mean level of plasma IL-18 than controls (309.6+/-138.6 versus 285.4+/
      115.7pg IL-18/mL). Furthermore, plasma IL-18 concentration was significantly
      associated with coronary plaque area (r=0.17, p=0.009). This relationship
      remained in a partial correlation analysis adjusting for CRP (r=0.15, p=0.02),
      for IL-6 (r=0.15, p=0.02) and for both CRP and IL-6 (r=0.15, p=0.02). In
      addition, IL-18 levels were significantly associated with other cardiovascular
      risk factors, namely age, low density lipoprotein (LDL) cholesterol,
      triglycerides, high density lipoprotein (HDL) cholesterol, insulin, proinsulin,
      body mass index (BMI), systolic and diastolic blood pressure. CONCLUSION: The
      present work provides evidence that plasma IL-18 is increased in postinfarction
      patients and is associated with coronary atherosclerosis.

PMID- 16405896
TI  - Differential response of vascular smooth muscle cells to oxidized LDL in mouse
      strains with different atherosclerosis susceptibility.
AB  - Oxidized low-density lipoprotein (LDL) has numerous atherogenic properties,
      including induction of inflammatory genes, and vascular smooth muscle cells
      (VSMC) are involved in the development of atherosclerosis. In this study, we
      examined whether variations of VSMC in the capacity to oxidize LDL or in response
      to minimally modified LDL (MM-LDL) constitute a genetic component in
      atherosclerosis. VSMC were isolated from the aorta of two inbred mouse strains
      C57BL/6J (B6) and C3H, which differ markedly in susceptibility to
      atherosclerosis. LDL oxidation was assessed by measuring thiobarbituric acid
      reactive substance (TBARS) production. Responses to MM-LDL were evaluated by
      examining the expression of inflammatory genes involved atherosclerosis,
      including monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion
      molecule-1 (VCAM-1), and an oxidant stress gene, heme oxygenase-1 (HO-1). VSMC
      from the two strains exhibited a comparable ability to transform native LDL to
      oxidized LDL, whereas their response to MM-LDL differed markedly. MM-LDL resulted
      in dramatic induction of MCP-1, VCAM-1, and HO-1 mRNAs in the cells from B6 mice
      but exerted little effect in cells from C3H mice. MCP-1 and soluble VCAM-1
      protein levels in conditioned media were measured by ELISA. B6 cells produced
      significantly more MCP-1 and VCAM-1 proteins in response to MM-LDL than C3H
      cells. These data suggest that variation in the response of VSMC to oxidized LDL
      may contribute to the difference between B6 and C3H mice in atherosclerosis
      susceptibility.

PMID- 16405897
TI  - Remember-Know judgments and retrieval of contextual details.
AB  - The Remember-Know (R-K) task is commonly used to differentiate between
      recollection and familiarity-based recognition memory. To further validate this
      test, we assessed the number of contextual details available to participants
      after giving R or K responses. We also examined the effect of retention interval
      on the episodic character of memories by administering the R-K task after both 10
      minute and 1-week retention intervals. At 1 week, items receiving R responses
      were accompanied by a significant number of episodic details, while K responses
      were not. A large number of items that received R responses at the 10-minute
      delay received K responses at 1 week, and these items were not accompanied by
      episodic detail during the later test. Items that were judged familiar at 10
      minutes but were labeled as recollected at 1 week were also not accompanied by
      significant memory of the study episode, suggesting that these items were
      recollected from the first test session. Overall, the data are consistent with
      the idea that R responses, unlike K responses, are accompanied by memory for
      episodic detail, and that the loss of memory for episodic detail over time
      parallels the conversion of R responses to K responses.

PMID- 16405898
TI  - A comparison of cue competition in a simple and a complex design.
AB  - Recent evidence suggests that controlled reasoning processes play an important
      role in cue competition in human causal learning (see De Houwer, J., Beckers, T.,
      & Vandorpe, S. (2005). Evidence for the role of higher-order reasoning processes
      in cue competition and other learning phenomena. Learning &Behavior, 33(2), 239
      249, for a review). Until now, this evidence comes almost exclusively from
      studies with simple designs that involved only a limited number of cues. Little
      is known about the role of controlled reasoning processes when the design is more
      complex. It is important to examine this issue because the complexity of the
      design could determine the resources that are available for reasoning and thus
      the role that reasoning plays in cue competition. We directly compared cue
      competition in a simple and a complex design. The results showed that complexity
      of the design affected retrospective cue competition but not forward cue
      competition. More fine grained analyses with respect to retrospective cue
      competition showed that unovershadowing but not backward blocking differed
      significantly between complexity conditions.

PMID- 16405899
TI  - New small-scale cross-axis coil planet centrifuge. The design of the apparatus
      and its application to counter-current chromatographic separation of proteins
      with aqueous-aqueous polymer phase systems.
AB  - The cross-axis coil planet centrifuge (X-axis CPC) is useful for partitioning
      macromolecules with aqueous-aqueous polymer phase systems. The floor model we
      have built with a pair of separation columns had some shortcomings such as
      requirement of large space, short life of the flow tubes, and difficulty in
      installing columns. In order to improve the partition efficiency and the utility
      of counter-current chromatography (CCC), a new small-scale X-axis CPC was
      designed and fabricated in our laboratory. The down-sizing of the apparatus was
      done by reducing the scale to about 1/2 of our original model of X-1.5L type with
      several improvements. Performance of the apparatus was evaluated on protein
      separation using an aqueous-aqueous polymer phase system composed of polyethylene
      glycol 1000 and dibasic potassium phosphate with four multilayer coiled columns.
      A series of experiments revealed that the combination of right- and left-handed
      coils produced the best partition efficiencies for both lower and upper mobile
      phases by selecting the revolution direction. The overall results indicate that
      the head-tail elution mode substantially affects to the peak resolution and
      stationary phase retention. This new X-axis CPC would be useful for the
      separation of various kinds of biologically active compounds.

PMID- 16405900
TI  - Enantioselective analysis of monoterpenes in different grape varieties during
      berry ripening using stir bar sorptive extraction- and solid phase extraction
      enantioselective-multidimensional gas chromatography-mass spectrometry.
AB  - The stereoisomeric ratios of various genuine metabolites of linalool (furanoid
      and pyranoid linalool oxides, hotrienol) and citronellol (cis- and trans-rose
      oxide) were determined in grape berries by means of enantioselective
      multidimensional gas chromatography-mass spectrometry. Stereoisomers of the
      metabolites could be separated on a chiral column with a modified cyclodextrin as
      stationary phase. The detailed stereoselective analysis of the furanoid and
      pyranoid linalool oxides in the cv. Morio-Muskat during berry ripening is giving
      evidence that furanoid linalool oxides are generated via two different reaction
      pathways. Additionally, stereoselective analysis of rose oxide in different
      varieties that have attained commercial maturity has been performed demonstrating
      that cis-(2S,4R)-rose oxide is the main stereoisomer in all varieties. (3S)
      Hotrienol was the main stereoisomer in all varieties with enantiomeric purities
      that were always higher than 90%.

PMID- 16405901
TI  - 5-(Hydroxymethyl)-2-furfural: a selective inhibitor of DNA polymerase lambda and
      terminal deoxynucleotidyltransferase.
AB  - 5-(Hydroxymethyl)-2-furfural (HMF), a pyrolysate of carbohydrate isolated from
      instant coffee (Coffea arabica L.), selectively inhibits the activities of
      mammalian DNA polymerase lambda (pol lambda) and terminal
      deoxynucleotidyltransferase (TdT) which are family X pols, in vitro. The compound
      influenced neither the activities of replicative DNA polymerases such as alpha,
      delta, and epsilon, nor even the activity of pol beta which is from the same
      family and thought to have a very similar three-dimensional structure to the pol
      beta-like region of pol lambda. Since parts of HMF such as furan, furfuryl
      alcohol, and 2-furaldehyde did not influence the activities of any enzymes
      tested, the substituted form of furan with a hyroxymethyl group and a formyl
      group might be important for the inhibition of pol lambda and TdT. The inhibitory
      effect of HMF on intact pol lambda (i.e., residues 1-575), a truncated pol lambda
      lacking the N-terminal BRCA1 C-terminus domain (133-575, del-1 pol lambda) and
      another truncated pol lambda lacking the N-terminal proline-rich region (245-575,
      del-2 pol lambda) was dose-dependent, and 50% inhibition was observed at a
      concentration of 26.1, 10.3, and 4.6 microM, respectively. The IC(50) value of
      HMF for TdT was the same as that for del-2 pol lambda (5.5 microM). The HMF
      induced inhibition of both pol lambda and TdT activities was competitive with
      respect to both the DNA template-primer and the dNTP substrate. On the basis of
      these results, HMF was suggested to bind to the pol beta-like region of pol
      lambda and TdT.

PMID- 16405902
TI  - Effect of five triterpenoid compounds isolated from root bark of Aralia elata on
      stimulus-induced superoxide generation, tyrosyl or serine/threonine
      phosphorylation and translocation of p47(phox), p67(phox), and rac to cell
      membrane in human neutrophils.
AB  - Five triterpenoids; Congmuyanoside V, X, XI, XII, and XV (Cong. V, X, XI, XII,
      and XV) were isolated from the root bark of Aralia elata. The effect of these
      triterpenoids on stimulus-induced superoxide generation in human neutrophils was
      assayed by measuring the reduction of ferricytochrome c (cyt. c) using a dual
      beam spectrophotometer. Translocation of p47(phox), p67(phox), and rac to the
      cell membrane and tyrosyl or serine/threonine phosphorylation of neutrophil
      proteins were investigated using specific monoclonal antibodies. The five
      triterpenoids used in the present experiment significantly suppressed N-formyl
      methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in
      concentration-dependent manner. Congmuyanoside V, XII, and XV also suppressed
      arachidonic acid (AA)-induced superoxide generation in high concentration.
      However, these triterpenoids showed no effect on phorbol 12-myristate 13-acetate
      (PMA)-induced superoxide generation. fMLP- and AA-induced tyrosyl phosphorylation
      and translocation of the cytosolic proteins p47(phox), p67(phox), and rac to the
      cell membrane were suppressed in parallel with the suppression of the stimulus
      induced superoxide generation.

PMID- 16405904
TI  - Effects of co-operative ligand binding on protein amide NH hydrogen exchange.
AB  - Amide protection factors have been determined from NMR measurements of
      hydrogen/deuterium amide NH exchange rates measured on assigned signals from
      Lactobacillus casei apo-DHFR and its binary and ternary complexes with
      trimethoprim (TMP), folinic acid and coenzymes (NADPH/NADP(+)). The substantial
      sizes of the residue-specific DeltaH and TDeltaS values for the opening/closing
      events in NH exchange for most of the measurable residues in apo-DHFR indicate
      that sub-global or global rather than local exchange mechanisms are usually
      involved. The amide groups of residues in helices and sheets are those most
      protected in apo-DHFR and its complexes, and the protection factors are generally
      related to the tightness of ligand binding. The effects of ligand binding that
      lead to changes in amide protection are not localised to specific binding sites
      but are spread throughout the structure via a network of intramolecular
      interactions. Although the increase in protein stability in the DHFR.TMP.NADPH
      complex involves increased ordering in the protein structure (requiring TDeltaS
      energy) this is recovered, to a large extent, by the stronger binding (enthalpic
      DeltaH) interactions made possible by the reduced motion in the protein. The
      ligand-induced protection effects in the ternary complexes DHFR.TMP.NADPH (large
      positive binding co-operativity) and DHFR.folinic acid.NADPH (large negative
      binding co-operativity) mirror the co-operative effects seen in the ligand
      binding. For the DHFR.TMP.NADPH complex, the ligand-induced protection factors
      result in DeltaDeltaG(o) values for many residues being larger than the
      DeltaDeltaG(o) values in the corresponding binary complexes. In contrast, for
      DHFR.folinic acid.NADPH, the DeltaDeltaG(o) values are generally smaller than
      many of those in the corresponding binary complexes. The results indicate that
      changes in protein conformational flexibility on formation of the ligand complex
      play an important role in determining the co-operativity in the ligand binding.

PMID- 16405903
TI  - p57Kip2 is induced by MyoD through a p73-dependent pathway.
AB  - The cyclin-dependent-kinase inhibitors p21 and p57 are highly expressed in
      skeletal muscle where they redundantly control cell cycle arrest during
      differentiation. We have previously shown that p57 is a target of the myogenic
      factor MyoD in cells lacking p21. Here we show that MyoD induces p57 at the
      transcriptional level through a mechanism different from that involved in p21
      regulation, since it is E-box-independent and requires new synthesized
      protein(s). We have identified p73 family members as the factors that mediate the
      activation of p57 through a 165bp promoter region. The levels of p73 alpha, beta
      and delta isoforms increase during muscle differentiation both in MyoD-expressing
      fibroblasts and in spontaneously differentiating C2 myoblasts. Moreover, the
      expression of a p73 dominant negative mutant interferes with the induction of
      p57. Finally, each of the isoforms up-regulated by MyoD, even when over-expressed
      alone, is capable of inducing p57 in p21-lacking fibroblasts. In contrast, the
      same p73 isoforms, either induced by MyoD or exogenously over-expressed, are
      unable to activate the expression of p57 in p21-expressing fibroblasts. Our
      finding that a transfected p57 promoter-reporter construct, unlike the endogenous
      gene, is responsive to both MyoD and p73 even in these cells, suggests that a cis
      acting mechanism, probably involving a repressive chromatin structure, prevents
      the induction of p57 in p21-expressing fibroblasts.

PMID- 16405905
TI  - UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain.
AB  - The ubiquitin-proteasome pathway is essential throughout the life cycle of a
      cell. This system employs an astounding number of proteins to ubiquitylate and to
      deliver protein substrates to the proteasome for their degradation. At the heart
      of this process is the large and growing family of ubiquitin receptor proteins.
      Within this family is an intensely studied group that contains both ubiquitin
      like (UBL) and ubiquitin-associated (UBA) domains: Rad23, Ddi1 and Dsk2. Although
      UBL/UBA family members are reported to regulate the degradation of other
      proteins, their individual roles in ubiquitin-mediated protein degradation has
      proven difficult to resolve due to their overlapping functional roles and
      interaction with each other and other ubiquitin family members. Here, we use a
      combination of NMR spectroscopy and molecular biology to reveal that Rad23 and
      Ddi1 interact with each other by using UBL/UBA domain interactions in a manner
      that does not preclude their interaction with ubiquitin. We demonstrate that
      UBL/UBA proteins can bind a common tetraubiquitin molecule and thereby provide
      strong evidence for a model in which chains adopt an opened structure to bind
      multiple receptor proteins. Altogether our results suggest a mechanism through
      which UBL/UBA proteins could protect chains from premature de-ubiquitylation and
      unnecessary elongation during their transit to the proteasome.

PMID- 16405906
TI  - Packing of the prion Ure2p in protein fibrils probed by fluorescence X-ray near
      edge structure spectroscopy at sulfur K-edge.
AB  - The soluble protein Ure2p from the yeast Saccharomyces cerevisiae assembles in
      vitro into straight and insoluble protein fibrils, through subtle changes of
      conformation. Whereas the structure of soluble Ure2p has been revealed by X-ray
      crystallography, further characterization of the structure of insoluble Ure2p
      fibrils is needed. We performed X-ray absorption near-edge spectroscopy (XANES)
      at the sulfur K-edge to probe the state of Cys221 in the fibrillar form of
      Ure2pC221 and provide structural information on the structure of Ure2p within
      fibrils. Although the Ure2p dimer dissociation into its constituent monomers has
      proven to be a prerequisite for assembly into fibrils, we showed the ability of
      every Ure2pC221 monomer to establish disulfide bonds upon incubation of the
      fibrils under oxidizing conditions. Our result indicates either that the
      constituent unit of the fibrillar form of the protein is a dimeric Ure2p or that
      the fibrils are made of protofilaments assembled in such a way that the residue
      C221 from a Ure2p molecule in one protofilament is located in the vicinity of a
      C221 residue from another molecule belonging to a neighbor protofilament.

PMID- 16405907
TI  - Bacillus subtilis bacteriophage SPP1 G40P helicase lacking the n-terminal domain
      unwinds DNA bidirectionally.
AB  - Bacillus subtilis bacteriophage SPP1 G40P hexameric replicative DNA helicase
      unidirectionally translocates with a 5'-->3' polarity while separating the DNA
      strands. A G40P mutant derivative lacking the N-terminal domain (containing amino
      acid residues 110-442 from G40P, G40PDeltaN109) was purified and characterized.
      G40PDeltaN109 showed an ATPase activity that was dependent on the presence of
      single-stranded (ss) DNA. Unlike G40P, G40PDeltaN109 was shown to bind with
      similar affinity both ssDNA arms of forked structures by nuclease protection
      assays. In a pH-dependent manner, G40PDeltaN109 unwound a branched double-arm
      substrate preferentially with a 3'-->5' polarity. Our results show that the
      linker region and the C-terminal domain of G40P are sufficient to render an
      enzyme capable of encircling the ssDNA tails of the forked DNA and to unwind DNA
      with both 5'-->3' and 3'-->5' polarity. The presence of the N-terminal domain,
      which does not play an essential role in helicase action, might be required
      indirectly for strand discrimination and polarity of translocation.

PMID- 16405908
TI  - Conformational diversity of ligands bound to proteins.
AB  - The phenomenon of molecular recognition, which underpins almost all biological
      processes, is dynamic, complex and subtle. Establishing an interaction between a
      pair of molecules involves mutual structural rearrangements guided by a highly
      convoluted energy landscape, the accurate mapping of which continues to elude us.
      Increased understanding of the degree to which the conformational space of a
      ligand is restricted upon binding may have important implications for docking
      studies, structure refinement and for function prediction methods based on
      geometrical comparisons of ligands or their binding sites. Here, we present an
      analysis of the conformational variability exhibited by three of the most
      ubiquitous biological ligands in nature, ATP, NAD and FAD. First, we demonstrate
      qualitatively that these ligands bind to proteins in widely varying
      conformations, including several cases in which parts of the molecule assume
      energetically unfavourable orientations. Next, by comparing the distribution of
      bound ligand shapes with the set of all possible molecular conformations, we
      provide a quantitative assessment of previous observations that ligands tend to
      unfold when binding to proteins. We show that, while extended forms of ligands
      are indeed common in ligand-protein structures, instances of ligands in almost
      maximally compact arrangements can also be found. Thirdly, we compare the
      conformational variation in two sets of ligand molecules, those bound to
      homologous proteins, and those bound to unrelated proteins. Although most
      superfamilies bind ligands in a fairly conserved manner, we find several cases in
      which significant variation in ligand configuration is observed.

PMID- 16405909
TI  - The crystal structure of polyhydroxybutyrate depolymerase from Penicillium
      funiculosum provides insights into the recognition and degradation of
      biopolyesters.
AB  - Polyhydroxybutyrate is a microbial polyester that can be produced from renewable
      resources, and is degraded by the enzyme polyhydroxybutyrate depolymerase. The
      crystal structures of polyhydroxybutyrate depolymerase from Penicillium
      funiculosum and its S39 A mutant complexed with the methyl ester of a trimer
      substrate of (R)-3-hydroxybutyrate have been determined at resolutions of 1.71 A
      and 1.66 A, respectively. The enzyme is comprised of a single domain, which
      represents a circularly permuted variant of the alpha/beta hydrolase fold. The
      catalytic residues Ser39, Asp121, and His155 are located at topologically
      conserved positions. The main chain amide groups of Ser40 and Cys250 form an
      oxyanion hole. A crevice is formed on the surface of the enzyme, to which a
      single polymer chain can be bound by predominantly hydrophobic interactions with
      several hydrophobic residues. The structure of the S39A mutant-trimeric substrate
      complex reveals that Trp307 is responsible for the recognition of the ester group
      adjacent to the scissile group. It is also revealed that the substrate-binding
      site includes at least three, and possibly four, subsites for binding monomer
      units of polyester substrates. Thirteen hydrophobic residues, which are exposed
      to solvent, are aligned around the mouth of the crevice, forming a putative
      adsorption site for the polymer surface. These residues may contribute to the
      sufficient binding affinity of the enzyme for PHB granules without a distinct
      substrate-binding domain.

PMID- 16405910
TI  - Folding transitions during assembly of the eukaryotic mRNA cap-binding complex.
AB  - The cap-binding protein eIF4E is the first in a chain of translation initiation
      factors that recruit 40S ribosomal subunits to the 5' end of eukaryotic mRNA.
      During cap-dependent translation, this protein binds to the 5'-terminal m(7)Gppp
      cap of the mRNA, as well as to the adaptor protein eIF4G. The latter then
      interacts with small ribosomal subunit-bound proteins, thereby promoting the mRNA
      recruitment process. Here, we show apo-eIF4E to be a protein that contains
      extensive unstructured regions, which are induced to fold upon recognition of the
      cap structure. Binding of eIF4G to apo-eIF4E likewise induces folding of the
      protein into a state that is similar to, but not identical with, that of cap
      bound eIF4E. At the same time, binding of each of the binding partners of eIF4E
      modulates the kinetics with which it interacts with the other partner. We present
      structural, kinetic and mutagenesis data that allow us to deduce some of the
      detailed folding transitions that take place during the eIF4E interactions.

PMID- 16405911
TI  - Structural characterization of the RyR1-FKBP12 interaction.
AB  - The 12 kDa FK506-binding protein (FKBP12) constitutively binds to the calcium
      release channel RyR1. Removal of FKBP12 using FK506 or rapamycin causes an
      increased open probability and an increase in the frequency of sub-conductance
      states in RyR1. Using cryo-electron microscopy and single-particle image
      processing, we have determined the 3D difference map of FKBP12 associated with
      RyR1 at 16 A resolution that can be fitted with the atomic model of FKBP12 in a
      unique orientation. This has allowed us to better define the surfaces of close
      apposition between FKBP12 and RyR1. Our results shed light on the role of several
      FKBP12 residues that had been found critical for the specificity of the RyR1
      FKBP12 interaction. As predicted from previous immunoprecipitation studies, our
      results suggest that Gln3 participates directly in this interaction. The
      orientation of RyR1-bound FKBP12, with part of its FK506 binding site facing
      towards RyR1, allows us to propose how FK506 is involved in the dissociation of
      FKBP12 from RyR1.

PMID- 16405913
TI  - The association between parenting stress, depressed mood and informant agreement
      in ADHD and ODD.
AB  - OBJECTIVE: In Attention Deficit Hyperactivity Disorder (ADHD) agreement between
      parents and teachers is often low. Parental depressed mood and parenting stress
      are considered to decrease informant agreement. This study examined informant
      agreement in children with ADHD and the association between parental depressed
      mood, parenting stress and agreement in the ratings of ADHD, ODD and CD symptoms.
      METHOD: 65 parents completed questionnaires on ADHD behavior of their child,
      parenting stress and depressed mood, teachers reported on ADHD behavior. RESULTS:
      Low agreement was found for hyperactive and moderate agreement for inattentive,
      ODD and CD symptoms. Stepwise regression analyses showed that parenting stress,
      and not parental depressed mood accounted for 12% of the variance in inattention
      symptoms disagreement, 14% of the variance in hyperactive symptoms disagreement
      and 9% in oppositional behavior disagreement. No significant predictors were
      found for CD disagreement. The found effect was independent of stimulant
      medication use. CONCLUSION: Parenting stress, but not parental depressed mood,
      was associated with the disagreement between parents and teachers on both ADHD
      and ODD symptoms. These results emphasize the importance of considering parenting
      stress in diagnosing ADHD and comorbid ODD.

PMID- 16405912
TI  - Recombinant human PPAR-beta/delta ligand-binding domain is locked in an activated
      conformation by endogenous fatty acids.
AB  - High-resolution crystallographic structures of recombinant human peroxisome
      proliferator-activated receptor ligand-binding domain (isotype beta/delta) reveal
      a fatty acid in the binding site. Mass spectrometry confirmed the presence of
      C16:0, C16:1, C18:0 and C18:1 in a ratio of approximately 3:2:1:4 with 11, Z
      octadecenoic acid (cis-vaccenic acid) identified as the predominant species.
      These are endogenous fatty acids acquired from the bacterial expression system,
      and serve to lock the ligand-binding domain into the activated conformation. A
      requirement for crystal growth, the additive n-heptyl-beta-d-glucopyranoside,
      binds near the activation function helix where recognition of co-activator
      proteins occurs. Our observations suggest potential physiological ligands for
      human PPAR-beta/delta and highlight that reported binding studies must be treated
      with caution unless endogenous fatty acids have been removed from the sample
      prior to analysis.

PMID- 16405915
TI  - U50488 inhibits outwardly rectifying potassium channel in PC12 cells via
      pertussis toxin-sensitive G-protein.
AB  - This study was undertaken to determine the effect of U50488, a kappa-opioid
      receptor agonist, on outwardly rectifying potassium channel (Ik) in
      undifferentiated PC12 cells. Using whole-cell and on-cell patch-clamp techniques,
      we found that U50488 decreased Ik amplitude in a time-dependent manner and Ik
      activation was delayed. Single-channel kinetic analysis provided a two-stage
      model for us to illuminate the blockage effect induced by U50488. To identify
      whether U50488 mediates the effect through opioid receptor and G-protein, several
      specific blockers and activators were used. Not only naloxone but also PTX and
      GDPbetaS abolished U50488-induced suppression; however, such effect was not
      observed when cAMP or other adenylyl cyclase activators were used. It is
      postulated that kappa-opioid receptor and Gi/o protein, but not cAMP, are
      involved in U50488-induced suppression of Ik.

PMID- 16405914
TI  - Genetic instability and clonal expansion.
AB  - Inactivation of tumor suppressor genes can lead to clonal expansion. We study the
      evolutionary dynamics of this process and calculate the probability that
      inactivation of a tumor suppressor gene is preceded by mutations in genes that
      confer genetic instability. Unstable cells might have a slower rate of clonal
      expansion than stable cells because of an increased probability of generating
      lethal mutations or inducing apoptosis. We show that the different growth rates
      of genetically stable and unstable cells during clonal expansion represent, in
      general, only a small disadvantage for genetic instability. The intuitive reason
      for this conclusion is that robust clonal expansion, where cellular birth rates
      are significantly greater than death rates, occurs on a much faster time scale
      than waiting for those mutations that allow clonal expansion. Moreover, in
      special cases where clonal expansion is very slow, genetically unstable cells
      have a higher probability to accumulate additional mutations during clonal
      expansion that confer a selective advantage. Clonal expansion represents a major
      disadvantage for genetic instability only when inactivation of the tumor
      suppressor gene leads to a very small increase of the cellular reproductive rate
      that is cancelled by the increased mortality of unstable cells.

PMID- 16405916
TI  - Suppression of porcine arterivirus replication by baculovirus-delivered shRNA
      targeting nucleoprotein.
AB  - The ability to synthesize shRNAs from DNA templates driven by RNA polymerase III
      promoters has made it possible to apply virus-derived vectors as delivery
      vehicles for double-strand RNA-mediated interference. Baculovirus emerges as a
      promising vector for in vivo gene therapy most recently. To investigate its
      potential as a delivery vector for anti-virus shRNA targeting arterivirus porcine
      reproductive and respiratory syndrome virus (PRRSV), we constructed recombinant
      baculovirus vectors bearing a shRNA-synthesizing cassette driven by U6 promoter
      with enhanced transduction efficiency by displaying vesicular stomatitis virus
      glycoprotein on viral envelope. Transduction of Marc145 cells with a recombinant
      baculovirus delivering egfp gene-specific shRNA dramatically suppressed the
      expression of EGFP in this cell line; and transduction of Marc145 cells with a
      baculovirus delivering shRNA specific for the C-terminal nucleoprotein coding
      region of PRRSV genome resulted in inhibition of viral replication. Our data
      highlight the recombinant baculovirus as an alternative vehicle for anti-virus
      shRNA delivery.

PMID- 16405917
TI  - Neurofibromin binds to caveolin-1 and regulates ras, FAK, and Akt.
AB  - Neurofibromin (Nf1) is an approximately 280 kDa protein having tumor suppressor
      function, presumably by virtue of its GTPase activating domain, but little is
      known regarding molecular aspects of its effector pathways. Caveolin-1 (Cav-1)
      regulates diverse signaling molecules and has itself been implicated as a tumor
      suppressor. Here we demonstrate that Nf1 binds to Cav-1's scaffolding domain and
      co-immunoprecipitates with Cav-1. Analysis of Nf1's primary structure reveals
      four potential caveolin binding domains, and interestingly, in individuals with
      neurofibromatosis I, missense mutations occur with high frequency in 3 of the 4
      putative domains. We show that Nf1 modulates ras, Akt, and focal adhesion kinase
      pathways, thereby affecting cytoskeletal organization; moreover, Nf1's effects on
      signaling are altered when lipid rafts and caveolae are disrupted by cholesterol
      depletion. These novel findings provide insight into possible signaling
      mechanisms of Nf1 and suggest that together Nf1 and Cav-1 may coordinately
      regulate cell growth and differentiation.

PMID- 16405918
TI  - Characterization of three novel imprinted snoRNAs from mouse Irm gene.
AB  - Most, if not all, of snoRNAs in mammals are intron-encoded, implying the
      expressional and functional relativeness between the snoRNA and their hosts. By
      computational analysis of an intron database extracted from 65 known mouse
      imprinted genes, three novel orphan box C/D snoRNAs were identified from Irm gene
      which is maternally expressed and related to human disorders. The snoRNAs were
      positively detected and found to express in all the mouse tissues except kidney.
      The imprinted snoRNAs exhibit stringent structures, but quite variable in
      locations at their host introns, suggesting their maturation probably through a
      splicing independent manner. We characterized Irm as a new kind of snoRNA host
      gene which has no protein-coding capacity and no 5'TOP structure in its mRNA. The
      newly identified snoRNAs appear mouse-specific, however, their function remains
      to be elucidated.

PMID- 16405919
TI  - Distinct regulation of gene expression in human endothelial cells by TGF-beta and
      its receptors.
AB  - Transforming growth factor beta (TGF-beta) and its signaling mediators play
      essential roles in angiogenesis-formation of new blood vessels, as evidenced by
      targeted gene disruption in mice and their mutations in human vascular dysplasia.
      However, little is known about the molecular basis of TGF-beta function in
      vascular formation. To study the function of TGF-beta signaling in angiogenesis
      and to elucidate the signaling specificity of TGF-beta receptors at the gene
      transcriptional level, we analyzed the expression profile of the genes regulated
      by TGF-beta and its type I receptors ALK1 and ALK5 in human microvessel
      endothelial cells (ECs). Global change of gene expression profiles was examined
      by microarray and RT-PCR analyses in the ECs treated with TGF-beta1 or by
      adenoviral expression of the active ALK1 or ALK5. We found that the profiles of
      the genes regulated by TGF-beta, ALK1 and ALK5 are distinct from each other,
      although some of genes are modulated by all of them. TGF-beta regulated far more
      genes than ALK1 and ALK5 did. ALK1 enhanced the formation of tube-like structures
      of ECs, while ALK5 stimulates EC aggregation. Our results suggest that ALK1
      appears to have important functions in regulating proliferation of ECs, whereas
      ALK5 tends to modulate cell-cell interaction and cell adhesion and extracellular
      matrix remodeling.

PMID- 16405920
TI  - Vitamin E inhibits hemolysis induced by hemin as a membrane stabilizer.
AB  - Hemin is a potential cytolytic agent. To test the effect of vitamin E on hemin
      mediated permeability in cell membranes, sheep erythrocytes were chosen as an
      appropriate model to study hemolysis induced by hemin. Hemin-induced hemolysis
      but did not elicit lipid peroxidation in sheep erythrocytes. Vitamin E was
      effective in inhibiting hemin-mediated hemolysis. Both chromanol ring and the
      isoprenoid side chain of tocopherols were essential for inhibition of hemin
      induced hemolysis. There was a strong correlation between the inhibitory effects
      of tocopherols on hemin-induced erythrocyte hemolysis and their effects on
      fluorescence anisotropy of cell membranes. Our results suggested that, in
      contrast to its antioxidant activity, vitamin E inhibits hemolysis induced by
      hemin as a membrane stabilizing agent.

PMID- 16405921
TI  - Characterization of the inhibitory activity of tenatoprazole on the gastric H+,K+
      -ATPase in vitro and in vivo.
AB  - Tenatoprazole is a prodrug of the proton pump inhibitor (PPI) class, which is
      converted to the active sulfenamide or sulfenic acid by acid in the secretory
      canaliculus of the stimulated parietal cell of the stomach. This active species
      binds to luminally accessible cysteines of the gastric H+,K+ -ATPase resulting in
      disulfide formation and acid secretion inhibition. Tenatoprazole binds at the
      catalytic subunit of the gastric acid pump with a stoichiometry of 2.6 nmol mg(
      1) of the enzyme in vitro. In vivo, maximum binding of tenatoprazole was 2.9 nmol
      mg(-1) of the enzyme at 2 h after IV administration. The binding sites of
      tenatoprazole were in the TM5/6 region at Cys813 and Cys822 as shown by tryptic
      and thermolysin digestion of the ATPase labeled by tenatoprazole. Decay of
      tenatoprazole binding on the gastric H+,K+ -ATPase consisted of two components.
      One was relatively fast, with a half-life 3.9 h due to reversal of binding at
      cysteine 813, and the other was a plateau phase corresponding to ATPase turnover
      reflecting binding at cysteine 822 that also results in sustained inhibition in
      the presence of reducing agents in vitro. The stability of inhibition and the
      long plasma half-life of tenatoprazole should result in prolonged inhibition of
      acid secretion as compared to omeprazole. Further, the bioavailability of
      tenatoprazole was two-fold greater in the (S)-tenatoprazole sodium salt hydrate
      form as compared to the free form in dogs which is due to differences in the
      crystal structure and hydrophobic nature of the two forms.

PMID- 16405922
TI  - Schisandrin B enhances doxorubicin-induced apoptosis of cancer cells but not
      normal cells.
AB  - The dose-dependent cardiotoxicities of doxorubicin (DOX) significantly limits its
      anti-cancer efficacies. One of the ways to augment the efficacies of DOX at a
      relatively low cumulative dose is to use a chemical sensitizer. Here, we
      demonstrated that schisandrin B (Sch B) significantly enhanced DOX-induced
      apoptosis of SMMC7721, a human hepatic carcinoma cell line, and of MCF-7, a human
      breast cancer cell line. This enhancement was irrelevant to the action of Sch B
      on P-glycoprotein or other drug-transporters, but associated with the activation
      of caspase-9 rather than caspase-8. The loss of mitochondria membrane potential
      was observed when cells were treated with DOX and Sch B combined. On the other
      hand, at the same experimental conditions, Sch B did not enhance the DOX-induced
      apoptosis of primary rat cardiomyocytes and primary human fibroblasts. Therefore,
      it is speculative that Sch B may bring benefit to clinical chemotherapy by
      reducing significantly the cumulative doses of DOX and its associated
      cardiotoxicities.

PMID- 16405923
TI  - Development of a superior frontal-intraparietal network for visuo-spatial working
      memory.
AB  - Working memory capacity increases throughout childhood and adolescence, which is
      important for the development of a wide range of cognitive abilities, including
      complex reasoning. The spatial-span task, in which subjects retain information
      about the order and position of a number of objects, is a sensitive task to
      measure development of spatial working memory. This review considers results from
      previous neuroimaging studies investigating the neural correlates of this
      development. Older children and adolescents, with higher capacity, have been
      found to have higher brain activity in the intraparietal cortex and in the
      posterior part of the superior frontal sulcus, during the performance of working
      memory tasks. The structural maturation of white matter has been investigated by
      diffusion tensor magnetic resonance imaging (DTI). This has revealed several
      regions in the frontal lobes in which white matter maturation is correlated with
      the development of working memory. Among these is a superior fronto-parietal
      white matter region, located close to the grey matter regions that are implicated
      in the development of working memory. Furthermore, the degree of white matter
      maturation is positively correlated with the degree of cortical activation in the
      frontal and parietal regions. This suggests that during childhood and
      adolescence, there is development of networks related to specific cognitive
      functions, such as visuo-spatial working memory. These networks not only consist
      of cortical areas but also the white matter tracts connecting them. For visuo
      spatial working memory, this network could consist of the superior frontal and
      intraparietal cortex.

PMID- 16405924
TI  - GTP uptake into rat brain synaptic vesicles.
AB  - Uptake of neurotransmitters into synaptic vesicles is driven by an
      electrochemical gradient generated by a vacuolar-type proton pump ATPase. This
      uptake implies a key role for synaptic vesicles in the regulation of
      neurotransmitter systems. Guanine nucleoside and nucleotides are involved in the
      inhibition of glutamate-induced cellular responses via an extracellular action
      and diverse trophic, proliferative, and modulatory effects of guanine nucleotides
      on neural cells have been shown. Here, we characterized the uptake of GTP into
      synaptic vesicles isolated from whole rat brain, by using a tritiated poorly
      hydrolyzable GTP analog, 5'-guanylylimidodiphosphate ([3H]GppNHp). Uptake of GTP
      into synaptic vesicles is saturable, time- and temperature-dependent, and relies
      on a proton-eletrochemical gradient. However, [3H]GMP and [3H]GDP radioactive
      labeling in synaptic vesicles is not dependent on temperature and vesicular
      ATPase activity, which indicates that these nucleotides only bind to and are not
      taken up into synaptic vesicles. GTP is taken up by the same eletrochemical
      gradient-dependent transport system, as are neurotransmitters storage, which
      indicates that this guanine nucleotide may also function as a neurotransmitter.

PMID- 16405926
TI  - Walking from thought.
AB  - Online analysis and classification of single electroencephalogram (EEG) trials
      during motor imagery were used for navigation in the virtual environment (VE).
      The EEG was recorded bipolarly with electrode placement over the hand and foot
      representation areas. The aim of the study was to demonstrate for the first time
      that it is possible to move through a virtual street without muscular activity
      when the participant only imagines feet movements. This is achieved by exploiting
      a brain-computer interface (BCI) which transforms thought-modulated EEG signals
      into an output signal that controls events within the VE. The experiments were
      carried out in an immersive projection environment, commonly referred to as a
      "Cave" (Cruz-Neira, C., Sandin, D.J., DeFanti, T.A., Surround-screen projection
      based virtual reality: the design and implementation of the CAVE. Proceedings of
      the 20th annual conference on Computer graphics and interactive techniques, ACM
      Press, 1993, pp. 135-142) where participants were able to move through a virtual
      street by foot imagery only. Prior to the final experiments in the Cave, the
      participants underwent an extensive BCI training.

PMID- 16405925
TI  - RNA interference targeting Akt promotes apoptosis in hypoxia-exposed human
      neuroblastoma cells.
AB  - Overactivation of the PI3 kinase/Akt pathway plays an essential role in the
      development and progression of various tumors. Akt is a key component of this
      pathway and hyperactivated in different tumors including neuroblastoma and
      glioma. In the present study, we tested the therapeutic efficacy of siRNA
      targeting Akt in inducing apoptotic cell death in NBFL cells (a human
      neuroblastoma cell line) subjected to anoxia/reoxygenation (A/R), a process that
      has been shown to modulate growth and progression of malignant tumors. We
      observed that siRNA targeting Akt effectively induced apoptotic cell death in
      NBFL cells (as determined by TUNEL assay and activated caspase-3
      immunoreactivity) under normoxic conditions, an effect that was greatly enhanced
      under conditions of A/R. These findings underscore the importance of Akt
      signaling in promoting survival of neuroblastoma cells and may have potential
      therapeutic applications.

PMID- 16405927
TI  - Presence of delta opioid receptors on a subset of hypothalamic gonadotropin
      releasing hormone (GnRH) neurons.
AB  - Opioid peptides exert an inhibitory effect on hypothalamic gonadotropin releasing
      hormone (GnRH) secretion mainly by interacting with mu-opioid receptors. Although
      a direct role for opioids via delta-opioid receptors (DORs) has been suggested,
      the presence of these receptors on GnRH neurons has never been demonstrated. In
      the present study, we determined the distribution of DORs in the basal
      hypothalamus of rat with special focus on their relation to GnRH neurons. Double
      labelling immunofluorescence and confocal microscopy revealed that DORs are
      exclusively present in a subpopulation of GnRH nerve terminals, with the highest
      density in the external layer of the median eminence. We then studied the
      functional characteristics of DORs in an immortalized GnRH-secreting neuronal
      cell line (GT1-1) known to endogenously express this receptor. Here, pertussis
      toxin pretreatment abolished the delta-agonist (DPDPE) inhibitory effect on cAMP
      accumulation. We also analyzed the type of G proteins involved in the signal
      transduced by the DOR and showed that GT1-1 cells express the inhibitory Go and
      Gi2 alpha-subunits. However, only Go was down-regulated under chronic DPDPE
      exposure. Finally, since DOR is expressed postnatally in brain, we compared GnRH
      neuronal cells immortalized at different developmental stages (the more mature
      GT1-1 and GT1-7 cells, versus the more immature GN11 cells), evidencing that only
      mature neurons express DOR. In conclusion, our study indicates that a direct
      control of opioids via delta-receptors occurs on GnRH neurons and validates the
      use of GT1 cells to further investigate the nature of the DOR present on GnRH
      neurons.

PMID- 16405928
TI  - A species-specific difference in the effects of harmaline on the rodent
      olivocerebellar system.
AB  - The rodent model of harmaline-induced tremor has been widely used for
      experimental analysis of tremor. Activation of the olivocerebellar system plays a
      key role in tremor-generating mechanisms. One undetermined problem is whether
      there are species-specific differences in effects of harmaline. The present study
      investigated effects of harmaline on olivocerebellar systems of mice and rats.
      Systemic administration of harmaline, but not vehicle, produced generalized, high
      frequency tremors in both types of rodents. Immunohistochemical studies revealed
      significant degeneration of Purkinje cells that was associated with activated
      microgliosis in the cerebellar cortex, following administration of harmaline in
      rats but not in mice. However, in mice but not rats, microgliosis was induced
      following administration of harmaline in the inferior olivary nucleus (ION),
      particularly in its caudal and medial subdivisions. Numbers of neurons in the
      mouse ION did not decrease, suggesting the possibility that microgliosis in ION
      might not be a simple neurotoxic effect. Presumably, differences in sensitivity
      of Purkinje cells between rats and mice may be related to differences in
      functional alterations in their respective olivocerebellar systems induced by
      harmaline. Recognition of these species-specific differences in the response of
      the olivocerebellar system to harmaline is an important consideration for
      experimental analysis of the rodent model of tremors.

PMID- 16405929
TI  - Understanding variety: tasting different foods delays satiation.
AB  - Variety stimulates intake by as much as 40% following both simultaneous and
      sequential presentations. Varying sensory and other characteristics of foods
      could sustain interest in eating and delay the development of satiation. Two
      experiments set out to explore this by investigating the effect of introducing
      different foods to taste and rate during intake of a snack. In Experiment 1, 33
      participants (23 female) attended the lab on four occasions, to eat sweet or
      salted popcorn (depending on preference). In a counterbalanced order participants
      ate ad libitum (control), or were interrupted during eating to taste and rate
      either the food they were eating (same condition: SC), another food with shared
      taste characteristics (congruent condition: CC) or a food with a different taste
      (incongruent condition: IC). Overall participants consumed significantly more in
      CC and IC than in SC [F(3,90) = 2.74, p<0.05], and pleasantness ratings of the
      eaten food during CC and IC remained high relative to SC, demonstrating a delay
      in the normal decline in pleasantness associated with satiation. In Experiment 2,
      47 participants (31 female) were allocated to either a food focus (FF) or food
      distraction (FD) condition, in which intake of chocolate was interrupted during
      eating to taste and rate chocolate only (FF) or this food and a cheese cracker
      (FD). FD (94 +/- 9.3 g) participants ate significantly more than FF (68 +/- 9.5
      g) and in support of findings from Experiment 1 pleasantness ratings during
      eating declined more rapidly during FF than FD. Variety may stimulate food
      intake, in part, by delaying the development of satiation which extends eating
      and therefore amount consumed. Encouraging consumers to focus on eating should
      facilitate the normal decline in pleasantness of the food and serve to limit
      intake.

PMID- 16405930
TI  - Reduced angiogenic responses in adult Endoglin heterozygous mice.
AB  - OBJECTIVE: To determine if angiogenesis is altered in adult Endoglin heterozygous
      (Eng(+/-)) mice, the animal model for the vascular disorder hereditary
      hemorrhagic telangiectasia type 1 (HHT1). METHODS: Primary cultures of
      endothelial cells were generated from Eng(+/-) and Eng(+/+) mice and analyzed for
      proliferation, migration, and ability to form capillary-like tubes. Endothelial
      cells derived from umbilical veins of newborns (HUVEC) with an HHT1 genotype were
      also tested for capillary formation. Two in vivo models of angiogenesis were
      tested in the Eng(+/-) and Eng(+/+) mice: Matrigel implant-dependent angiogenesis
      and reperfusion following hindlimb ischemia. RESULTS: The Eng(+/-) endothelial
      cells displayed significantly reduced proliferation and migration, increased
      collagen production, and decreased NO synthase expression and vascular
      endothelial growth factor (VEGF) secretion. They also showed impaired capillary
      tube formation in vitro, as did the HHT1 HUVEC. These endothelial cell-specific
      abnormalities were associated with impaired Matrigel-dependent capillary tube
      formation in vivo and delayed reperfusion following hindlimb ischemia.
      CONCLUSIONS: Although vascular development is normal in Eng(+/-) mice, angiogenic
      abnormalities were observed in the adult mice and their isolated endothelial
      cells. These results suggest that a normal level of endoglin is required for full
      angiogenic activity.

PMID- 16405931
TI  - Involvement of lipid rafts and caveolae in cardiac ion channel function.
AB  - A variety of lipid microdomains, including caveolae, have been shown to play an
      important role in both protein targetting and in controlling protein-protein
      interactions. There is increasing evidence for significant ion channel
      localization in lipid rafts. Cardiac channel subunits known to localize in lipid
      rafts include Kv1.4, Kv1.5, Kv2.1, Kv4, Kir2, Kir3, K(ATP), Nav and Cav subunits.
      This article reviews what is known about the occurrence and functional
      significance of cardiac ion channel/lipid raft interactions. Much remains to be
      learned about this area of potentially enormous importance to cardiac function in
      health and disease.

PMID- 16405932
TI  - Accumulation of coumarins in Arabidopsis thaliana.
AB  - The biosynthesis of coumarins in plants is not well understood, although these
      metabolic pathways are often found in the plant kingdom. We report here the
      occurrence of coumarins in Arabidopsis thaliana ecotype Columbia. Considerably
      high levels of scopoletin and its beta-d-glucopyranoside, scopolin, were found in
      the wild-type roots. The scopolin level in the roots was approximately
      1200nmol/gFW, which was approximately 180-fold of that in the aerial parts. Calli
      accumulated scopolin at a level of 70nmol/gFW. Scopoletin and scopolin formation
      were induced in shoots after treatment with either 2,4-dichlorophenoxyacetic acid
      (at 100microM) or a bud-cell suspension of Fusarium oxysporum. In order to gain
      insight into the biosynthetic pathway of coumarins in A. thaliana, we analyzed
      coumarins in the mutants obtained from the SALK Institute collection that carried
      a T-DNA insertion within the gene encoding the cytochrome P450, CYP98A3, which
      catalyzes 3'-hydroxylation of p-coumarate units in the phenylpropanoid pathway.
      The content of scopoletin and scopolin in the mutant roots greatly decreased to
      approximately 3% of that in the wild-type roots. This observation suggests that
      scopoletin and scopolin biosynthesis in A. thaliana are strongly dependent on the
      3'-hydroxylation of p-coumarate units catalyzed by CYP98A3. We also found that
      the level of skimmin, a beta-d-glucopyranoside of umbelliferone, was slightly
      increased in the mutant roots.

PMID- 16405933
TI  - Altitudinal variation of secondary metabolite profiles in flowering heads of
      Arnica montana cv. ARBO.
AB  - The altitudinal variation on the contents of secondary metabolites in flowering
      heads of Arnica montana was assessed. Plants of A. montana cultivar ARBO were
      grown in nine experimental plots at altitudes between 590 and 2230m at Mount
      Patscherkofel near Innsbruck/Austria. The total contents of sesquiterpene
      lactones and flavonoids were not positively correlated with the altitude of the
      growing site. However, the proportion of flavonoids with vicinal free hydroxy
      groups in ring B to flavonoids lacking this feature significantly increased with
      elevation. Additionally, the level of caffeic acid derivatives also positively
      correlated with the altitude of the growing site. In particular amounts of 1
      methoxyoxaloyl-3,5-dicaffeoylquinic acid significantly increased in higher sites
      and samples from the summit region contained 85% more of this compound than
      samples from valley sites. These results are discussed with regards to
      chemosystematic studies comparing samples collected in different altitudes as
      well as in the light of a UV-B protective and radical scavenging function of
      phenolics and their significance for plant life in environments with elevated UV
      B radiation.

PMID- 16405935
TI  - Chloroquine-induced bilateral ptosis.
AB  - This report describes a case of bilateral ptosis induced by chloroquine.
      Chloroquine treatment remains the most common single treatment of malaria in sub
      Saharan Africa. Ptosis occurring 24 h after chloroquine therapy, with full
      recovery 48 h after cessation of chloroquine, has not been described previously.
      Documentation of adverse events for safe and commonly used drugs is important.

PMID- 16405934
TI  - A cytokine promoter/yellow fluorescent protein reporter transgene serves as an
      early activation marker of lymphocyte subsets.
AB  - A mouse containing an IL-4 promoter linked to the yellow fluorescent protein
      (YFP) reporter transgene was created to follow aspects of lymphocyte development
      and function. Following stimulation with phorbol 12-myristate 13-acetate and
      ionomycin, anti-CD3/CD28, antigen-specific peptide, or allogeneic cells, both CD4
      and CD8 T cells expressed the transgene within 24h in a manner that was
      consistent with cellular activation markers. Transgene induction was inhibited by
      cyclosporine and FK506, suggesting that its activation occurs in an NFAT
      dependent manner. B lymphocytes were also able to express the transgene when
      stimulated with LPS. This induction was inhibited in part by rapamycin. The
      results suggest that this transgene can function as an indicator of lymphocyte
      activation. Because YFP is not toxic and requires no preparation of the cells to
      view the reporter gene, this system provides a unique tool to follow lymphocyte
      activation in a number of model systems, such as those involving transplantation,
      allergy, and vaccine development.

PMID- 16405936
TI  - Separation of time scales, fixation probabilities and convergence to
      evolutionarily stable states under isolation by distance.
AB  - To a first order of approximation, selection is frequency independent in a wide
      range of family structured models and in populations following an island model of
      dispersal, provided the number of families or demes is large and the population
      is haploid or diploid but allelic effects on phenotype are semidominant. This
      result underlies the way the evolutionary stability of traits is computed in
      games with continuous strategy sets. In this paper similar results are derived
      under isolation by distance. The first-order effect on expected change in allele
      frequency is given in terms of a measure of local genetic diversity, and of
      measures of genetic structure which are almost independent of allele frequency in
      the total population when the number of demes is large. Hence, when the number of
      demes increases the response to selection becomes of constant sign. This result
      holds because the relevant neutral measures of population structure converge to
      equilibrium at a rate faster than the rate of allele frequency changes in the
      total population. In the same conditions and in the absence of demographic
      fluctuations, the results also provide a simple way to compute the fixation
      probability of mutants affecting various ecological traits, such as sex ratio,
      dispersal, life-history, or cooperation, under isolation by distance. This result
      is illustrated and tested against simulations for mutants affecting the dispersal
      probability under a stepping-stone model.

PMID- 16405937
TI  - Rapid immunoassay for the determination of glial fibrillary acidic protein (GFAP)
      in serum.
AB  - BACKGROUND: This study was aimed to develop a sensitive and rapid assay for the
      determination of glial fibrillary acidic protein (GFAP) in serum and to evaluate
      the clinical applicability in serum samples from patients with acute stroke.
      METHODS: The two-site chemiluminometric immunoassay, intended to use in a near
      patient setting with a single incubation step (20 min), was used to measure serum
      samples from healthy blood donors and from patients with brain injury and
      correlated to serum S100B levels. RESULTS: The GFAP assay covered a concentration
      range up to 18 microg/L with an analytical sensitivity of 0.014 microg/L. The
      intra-assay precision was 3.5% at 1.55 microg/L (n=20) and 4.1% at 0.39 microg/L
      (n=20). The inter-assay precision was 3.8% at 9.1 microg/L (n=10) and 10.3 % at
      0.21 microg/L (n=9). Normal controls (n=46) showed non-detectable GFAP with a 99%
      upper limit of <0.04 microg/L. GFAP values were associated with progression and
      severity of the illness in acute stroke patients. CONCLUSIONS: We have developed
      an improved assay for the measurement of GFAP levels in serum. Serum GFAP is a
      potential marker for prognosis and outcome in patients with central nervous
      system disorders.

PMID- 16405938
TI  - Prognostic significance of ischemia modified albumin after percutaneous coronary
      intervention.
AB  - Ischemia modified albumin (IMA) is a new biochemical marker of ischemia. IMA
      levels rise in patients who develop ischemia during percutaneous coronary
      intervention (PCI). It is unclear whether IMA elevations correlate with PCI
      variables. The possible prognostic value of post-PCI IMA elevation has not yet to
      be studied. METHODS: We studied 60 patients (mean age 61 years; 51 male) who
      underwent successful elective single-vessel PCI for the management of stable
      angina pectoris. IMA levels were measured and compared with PCI variables and
      target lesion revascularization rate. The median post-PCI follow up is 46 months
      (CI 44.6 to 47.7). RESULTS: We found that the only variable related to post-PCI
      IMA levels was periprocedural dissection of target vessel (147.6 vs. 141.1 kU/l,
      p=0.035). No correlation between high and low balloon inflation pressure (143.6
      vs. 141.6 kU/l, p=0.64), short and long inflation pressure (141.5 vs. 143.6 kU/l,
      p=0.17), with and without stent placement (143.7 vs. 141.3 kU/l, p=0.93) was
      found. IMA level more then 130 kU/l was associated with higher frequency of
      target lesion revascularization at nearly 4-years follow-up (p=0.026).
      CONCLUSION: Post-PCI IMA elevation is associated with higher target lesion
      revascularization.

PMID- 16405939
TI  - CYP1A2 and NAT2 phenotyping and 3-aminobiphenyl and 4-aminobiphenyl hemoglobin
      adduct levels in smokers and non-smokers.
AB  - Some aromatic amines are considered to be putative bladder carcinogens.
      Hemoglobin (Hb) adducts of 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP)
      have been used as biomarkers of exposure to aromatic amines from cigarette smoke.
      One of the goals of this study was to determine intra- and inter-individual
      variability in 3-ABP and 4-ABP Hb adducts and to explore the predictability of
      ABP Hb adduct levels based on caffeine phenotyping. The study was conducted in
      adult smokers (S, n = 65) and non-smokers (NS, n = 65). The subjects were
      phenotyped for CYP1A2 and NAT2 using urinary caffeine metabolites. Blood samples
      were collected twice within 6 weeks and adducts measured by GC/MS. The levels of
      4-ABP Hb adducts were significantly (p < 0.0001) greater in S (34.5 +/- 21.06
      pg/g Hb) compared to NS (6.3 +/- 3.02 pg/g Hb). The levels of 3-ABP Hb adducts
      were below the limit of quantification (BLOQ) in most (82%) of the NS and about
      10-fold lower in S (3.6 +/- 3.29 pg/g Hb) compared to 4-ABP Hb adducts. No
      differences were observed in the adduct levels between weeks 1 and 6 in the
      smokers, suggesting that a single sample would be adequate to monitor cigarette
      smoke exposure. The regression model developed with CYP1A2, NAT2 phenotype and
      number of cigarettes smoked (NCIG) accounted for 47% of the variability in 3-ABP
      adducts, whereas 32% variability in 4-ABP adducts was accounted by CYP1A2 and
      NCIG. The ratio of 4-ABP Hb adducts in adult S:NS was approximately 5:1, whereas
      3-ABP Hb adducts levels were BLOQ in some S, exhibited large interindividual
      variability ( approximately 91% compared to 57% for 4-ABP Hb) and poor dose
      response relationship. Therefore, 4-ABP Hb adduct levels may be a more useful
      biomarker of aminobiphenyl exposure from cigarette smoke.

PMID- 16405940
TI  - The flash-lag effect is reduced when the flash is perceived as a sensory
      consequence of our action.
AB  - The flash-lag effect (FLE) is defined as an error in localization that consists
      of perceiving a flashed object to lag behind a moving one when both are presented
      in physical alignment. Previous studies have addressed the question if it is the
      predictability of the flash, or the moving object, that modulates the amount of
      the error. However, the case when the flash is self-generated, and hence can be
      internally predicted, has not yet been addressed. In Experiment 1, we compare
      four conditions: flash unpredictable, flash externally predicted by a beep, flash
      internally generated (and predicted) by pressing a key, and flash triggered by a
      key press but temporally unpredictable. The FLE was significantly reduced only
      when the flash was internally predictable. In Experiment 2, we rule out the
      possibility that the reduction of the FLE was due to the use of the key press as
      a temporal marker. We conclude that when the flash is perceived as a sensory
      consequence of our own action, its detection can be speeded up, thereby resulting
      in a reduction of the FLE. A third experiment supports this interpretation. The
      mechanism by virtue of which the detection is accelerated could be related to
      efferent signals from motor areas predicting the sensory consequences of our
      actions.

PMID- 16405941
TI  - Solving an enigma: arterial pole development in the zebrafish heart.
AB  - It is a widely held belief that the arterial pole of the zebrafish heart is
      unusual among models of comparative cardiogenesis. This is based, in part, on the
      report that the bulbus arteriosus undergoes a striated-to-smooth muscle
      phenotypic transition during development. An implication of this is that the
      zebrafish, a model almost ubiquitously accepted in other fields of comparative
      biology, may be poorly suited to the study of conotruncal abnormalities in human
      disease. However, while the use of atrioventricular-specific molecular markers
      has allowed extensive characterization of the development of the atrium and
      ventricle, the lack of any bulbus-specific markers has meant that this region of
      the zebrafish heart is poorly characterized and quite possibly misunderstood. We
      have discovered that the fluorescent nitric oxide indicator 4,5
      diaminofluorescein diacetate (DAF-2DA) specifically labels the bulbus arteriosus
      throughout development from approximately 48 h post-fertilization. Therefore,
      using DAF-2DA and an immunohistochemical approach, we attempted to further
      characterize the development of the bulbus. We have concluded that no such
      phenotypic transition occurs, that contrary to current thinking, aspects of
      zebrafish arterial pole development are evolutionarily conserved, and that the
      bulbus should not be considered a chamber, being more akin to the arterial
      trunk(s) of higher vertebrates.

PMID- 16405942
TI  - Lincomycin solar photodegradation, algal toxicity and removal from wastewaters by
      means of ozonation.
AB  - Antibiotic molecules have been reported among the xenobiotics present at trace
      levels in sewage treatment plant (STP) effluents and aquatic environment.
      Lincomycin, one of the most used in clinical practices whose presence in the STP
      effluents has been often documented, is submitted to an extensive investigation
      to assess its persistence in the environment and toxicity towards different algal
      strains. The possibility to remove the lincomycin from water by means of
      ozonation is demonstrated and a reduction of toxicity of ozonated solutions on S.
      leopoliensis, with respect to untreated solutions containing this compound, is
      obtained even just for 1h of treatment. Kinetic constants for the attack to
      lincomycin of ozone (from 1.53 x 10(5) M(-1)s(-1) at pH = 3.0 and 4.93 x 10(5) M(
      1)s(-1) at pH = 6.7) and OH radicals (4.37 x 10(9) M(-1)s(-1) at pH = 5.5 and
      4.59 x 10(9) M(-1)s(-1) at pH = 7.5) are also evaluated.

PMID- 16405944
TI  - Dispersion and treatment performance analysis of an UASB reactor under different
      hydraulic loading rates.
AB  - Mixing and transport phenomena affect the efficiency of all bioreactor
      configurations. An even mixing pattern at the macro-level is desirable to provide
      good conditions for substrate transport to, and from, the microbial aggregates.
      The state of segregation of particulate material in the reactor is also
      important. The production of biogas in anaerobic reactors is another factor that
      affects mixing intensity and hence the interactions between the liquid, solid and
      gaseous phases. The CSTR model with some degree of short-circuiting, dead zones
      and bypassing flows seems to describe the overall hydrodynamics of UASBs.
      However, few data are available in the literature for full-scale reactors that
      relate process performance to mixing characteristics. Dispersion studies using
      LiCl were done for four hydraulic loading rates on a full-scale UASB treating
      domestic wastewater in Ginebra, Valle del Cauca, southwest Colombia. COD, TSS,
      and Settleable Solids were used to evaluate the performance of organic matter
      removal. The UASB showed a complete mixing pattern for hydraulic loading rates
      close to the design value (i.e. Q = 10-13l s(-1) and HRT=8-6 h). Gross mixing
      distortions and localised stagnant zones, short-circuiting and bypass flows were
      found in the sludge bed and blanket zones for both extreme conditions
      (underloading and overloading). The liquid volume contained below the gas-liquid
      solid separator was found to contribute to the overall stagnant volume,
      particularly when the reactor was underloaded. The removal of organic matter
      showed a log-linear correlation with the dispersion number.

PMID- 16405943
TI  - Towards a "crippled-mode" operation of an industrial wastewater treatment plant.
AB  - In house treatment of metal plating wastewater mainly involves chemical
      treatments performed in continuous flow stirred tank reactors (CFSTR). The inflow
      of these tanks is directly produced by the plating shops activity, and the
      storage capacity never exceeds a few hours of incoming flow. Thus, any fault on
      one of the CFSTR may impose a complete stop of the whole manufacturing process,
      which is unacceptable for the manufacturer. Another solution would be having
      "spare" CFSTRs ready to be used as alternative in case of any CFSTR fault or
      maintenance. The latter solution however implies additional costs in equipment,
      storage space and maintenance so as to keep this equipment fit and ready for
      operation. The paper presents the study of a "crippled-mode" wastewater treatment
      (WWT) operation which enables a sufficiently efficient working of the WWT plant
      during maintenance phases and failure repairing on any of the CFSTR, without any
      extra equipment needed. This survey has been performed on real industrial WWT
      plants, with a continuous influent and under industrial operation constraints.
      The performances of the detoxication have been analysed when a CFSTR is short
      circuited and the corresponding chemical treatment is shunt in the upstream or
      downstream CSFTR. This work shows the possibility of satisfying the environmental
      regulations with a WWT plant functioning under subnormal conditions.

PMID- 16405945
TI  - Biokinetics of biodegradation of surfactants under aerobic, anoxic and anaerobic
      conditions.
AB  - The present investigation aims at estimating the biodegradation coefficients of
      surfactants. The biodegradabilities of Triton X-100 and Rhamnolipid were tested
      under aerobic, nitrate reducing, sulphate reducing and anaerobic conditions using
      a respirometer. The results indicated that in terms of biodegradability,
      Rhamnolipid is superior to Triton X-100, since it is biodegradable under all
      conditions, whereas Triton X-100 is partially biodegradable under aerobic
      conditions and non-biodegradable under anaerobic, nitrate reducing and sulphate
      reducing conditions.

PMID- 16405946
TI  - Characterization of tributyltin in shipyard waters and removal through laboratory
      and full-scale treatment.
AB  - Characterization and treatment studies were conducted in an effort to evaluate
      treatment options capable of removing tributyltin (TBT) in shipyard waters from
      above 1,000,000 ng/L to effluent concentrations below 50 ng/L. Laboratory studies
      and operation of a full-scale treatment plant were used to examine treatment
      options for TBT removal and included physicochemical treatment processes of
      coagulation-clarification, filtration, and granular activated carbon (GAC)
      adsorption. Significant variability was observed in TBT-containing shipyard
      waters (generated from different ships) in terms of their particulate solids,
      conductivity, and TBT and dissolved organic carbon concentrations. Laboratory
      tests with aluminum sulfate and ferric sulfate showed that on average 90% of TBT
      in shipyard waters could be removed by coagulation-flocculation-clarification
      under optimum conditions. No statistically significant difference was found in
      TBT removal capabilities between the two metal salts when compared at equivalent
      metal doses and coagulation pH. Much lower removals were observed for the
      coagulation-flocculation-clarification portion of the full-scale plant while the
      complete full-scale treatment plant averaged 99.8% TBT removal over a period of 3
      years. While relatively high % removals were achieved, the total treatment
      process did not consistently remove TBT to levels that would meet the regulatory
      requirements proposed (50 ng/L) at the time the study was conducted. Based on the
      results from limited efforts to characterize the dissolved and particulate TBT
      fractions in the full-scale treatment plant effluent, particulate TBT was
      observed to be the dominant component of the effluent TBT from the full-scale
      plant and may be associated with polymer carry through.

PMID- 16405947
TI  - Delayed occurrence of H-ras12V-induced hepatocellular carcinoma with long-term
      treatment with cinnamaldehydes.
AB  - Cinnamaldehyde from the bark of Cinnamomum cassia has been reported to have
      antitumor activity mediated by the inhibition of farnesyl transferase. We
      assessed in vivo the chemo-preventive effect of cinnamaldehydes on H-ras12V
      induced hepatocellular carcinoma formation. A mouse model of hepatocellular
      carcinoma was established by using the transgene of mutated H-ras12V under the
      regulation of albumin enhancer/promoter. When treated with cinnamaldehyde for 10
      weeks, hepatic tumor development was delayed with 2'-benzoyloxycinnamaldehyde
      (BCA) compared with control hepatocellular carcinoma formation. The effect of 2'
      hydroxycinnamaldehyde (HCA) was comparable. The number of lesions and the size of
      each lesion were significantly reduced by BCA. Cell proliferation in the lesion
      was detected by incorporation of 5-bromo-2'-deoxyuridine (BrdU). BCA increased
      the number of splenocytes, concanavalin A-stimulated splenocyte proliferation and
      the infiltration of lymphocytes into liver. Data suggest that the delayed hepatic
      tumor development observed with BCA could be mediated by a long-term
      immunostimulating effect on T cells.

PMID- 16405948
TI  - Heavy metal detoxification in eukaryotic microalgae.
AB  - Microalgae are aquatic organisms possessing molecular mechanisms that allow them
      to discriminate non-essential heavy metals from those essential ones for their
      growth. The different detoxification processes executed by algae are reviewed
      with special emphasis on those involving the peptides metallothioneins, mainly
      the post transcriptionally synthesized class III metallothioneins or
      phytochelatins. Also, the features that make microalgae suitable organisms
      technologies specially to treat water that is heavily polluted with metals is
      discussed.

PMID- 16405949
TI  - Prediction of ozone concentrations in Oporto city with statistical approaches.
AB  - The performance of three statistical methods: time-series, multiple linear
      regression and feedforward artificial neural networks models were compared to
      predict the daily mean ozone concentrations. The study here reported was based on
      data from one urban site with traffic influences and one rural background site.
      The studies were performed for the year 2002 and the respective four trimesters
      separately. In the multiple linear regression and feedforward artificial neural
      network models, the concentrations of ozone, the concentrations of its precursors
      (nitrogen oxides) and some meteorological variables for one and two days before
      the prediction day were used as predictors. For the application of these models
      in the validation step, the inputs of ozone concentration for one and two days
      before were replaced by the ozone concentrations predicted by the models. The
      results showed that time-series modelling was not profitable. In the development
      step, similar performances were obtained with multiple linear regression and
      feedforward artificial neural network. Better performance indexes were achieved
      with feedforward artificial neural network models in validation step. Concluding,
      feedforward artificial neural network models were more efficient to predict ozone
      concentrations.

PMID- 16405950
TI  - Studies on the adsorption and kinetics of photodegradation of a model compound
      for heterogeneous photocatalysis onto TiO(2).
AB  - An investigation was made on the adsorption and kinetics of photodegradation of
      potassium hydrogenphthalate in an aqueous suspension of TiO(2). Two models,
      Langmuir and Freundlich, were used to describe the adsorption process and the
      model proposed by Langmuir-Hinshelwood (L-H) was employed to describe the
      kinetics of the photodecomposition reactions of hydrogenphthalate. The results of
      the adsorptions were fitted to the models proposed by Langmuir and Freundlich.
      Adsorption was found to be a function of the temperature, with adsorption
      capacity increasing from 2.4 to 4.5 mg/g when the temperature rose from 20 to 30
      degrees C. The kinetic model indicates that the rate constant, k, of the first
      order reaction, is high in the 10.0 to 100 mg/l interval, which is coherent with
      the low value of the adsorption constant, K. The results fitted to the L-H model
      led to an equation that, within the range of concentrations studied here,
      theoretically allows one to evaluate the photodegradation rate.

PMID- 16405951
TI  - Multi-generational effects of four selected environmental oestrogens on Daphnia
      magna.
AB  - The objective of this study was to determine whether vertebrate-type oestrogens
      have ecotoxicological effects on a crustacean species. The effects of 17beta
      oestradiol (E2), diethylstilbestrol (DES), bisphenol A (BPA) and 4-nonylphenol (4
      NP) on the freshwater invertebrate Daphnia magna were assessed over first and
      second generations. The acute EC(50) 48 h, based on immobilisation, for E2, DES,
      BPA and 4-NP were 2.87 mg/l, 1.55 mg/l, 7.75 mg/l and 0.13 mg/l, respectively.
      The impact of the test chemicals on moulting frequency was also assessed. The
      EC(50) 48 h, based on the inhibition of moult number for E2, DES and 4-NP were
      2.04 mg/l, 1.87 mg/l and 0.14 mg/l, respectively. BPA was not observed to impact
      the moulting frequency of D. magna at concentrations tested. In a series of
      separate studies, the effects of the four selected test compounds on the
      survival, moulting frequency and reproduction of first and second generational D.
      magna were assessed over a period of 21 d. Exposure of D. magna to 4-NP decreased
      the number of offspring produced in both first and second generation testing. DES
      proved to have no significant (p0.05) inhibition of fecundity in first generation
      but when second generation daphnids were exposed to DES, a significant (p0.05)
      reduction in the number of offspring was recorded. When D. magna were exposed to
      E2 or BPA, no statistically significant (p0.05) inhibition in the number of
      moults or offspring produced was observed.

PMID- 16405952
TI  - House dust as a source of human exposure to polybrominated diphenyl ethers in
      Kuwait.
AB  - This study reports concentrations of polybrominated diphenyl ethers (PBDEs) in
      dust samples collected from 17 homes in Kuwait. PBDEs were measured in all homes
      investigated with mean summation operatorPBDEs concentration ranging from 1 to
      393 ng g(-1), with a geometric mean of 76 ng g(-1). The dominant congener in all
      samples was BDE 209 constituting ca. 85% of the summationPBDEs followed by BDE 99
      (5%), BDE 47 (4.5%), and BDE 183 (2%). The congener mixture in dust is dominated
      by those in deca and penta formulations. Using the measured concentrations and
      estimates of dust ingestion rates for children and adults, estimated human non
      dietary exposure based on mean PBDE levels were 14.8 and 1.5 ng day(-1) for
      children and adults, respectively. The 10-fold difference in exposure estimates
      between children and adults in this study supports previous reports that children
      are at greater risk from pollutants that accumulate indoors. The ubiquitous
      distribution of these chemicals as noted in this study highlights the fact that
      we are continuously exposed to low doses of chemicals in the indoor environment.

PMID- 16405953
TI  - Influence of organic matter on municipal solid waste incinerator bottom ash
      carbonation.
AB  - The biodegradation of organic matter in municipal solid waste incinerator (MSWI)
      bottom ash was studied in order to investigate the interaction between the CO(2)
      produced by microbial respiration and bottom ash. Respiration tests were
      performed on bottom ash at different moisture contents in an incubator at 30
      degrees C. O(2) consumption and CO(2) production were monitored and quantified.
      Leaching tests were carried out at the end of the experiments. Total organic
      carbon (TOC) leaching had decreased. Over a period of three weeks, pH decreased
      from 10.7 to 8.2 and bottom ash was considered to be fully carbonated. This
      showed that the organic matter found in bottom ash can provide a substrate for
      microbial activity. The CO(2) produced by microbial respiration was directly
      dissolved in bottom ash pore water in order to be mineralized in carbonate form.
      The origin of the carbon dioxide which induces maturation of bottom ash on
      weathering areas has never been really discussed and is often presumed to be
      atmospheric CO(2). However, biodegradation of organic matter could contribute for
      a large part to this phenomenon, depending on field-scale physico-chemical
      weathering conditions.

PMID- 16405954
TI  - Temporal evolution of polycyclic aromatic hydrocarbons (PAHs) in sludge from
      wastewater treatment plants: comparison between PAHs and heavy metals.
AB  - This paper presents results on the presence and temporal variability of the 16
      PAHs recommended by the EPA in primary, secondary and digested sewage sludge over
      a year. The sewage sludges originated from the Guadalete wastewater treatment
      plant (WWTP) site in Jerez de la Frontera (Cadiz, Spain). These organic
      pollutants have been extracted from the sewage sludge by microwave energy. High
      performance liquid chromatography coupled with diode array (HPLC-DAD) or
      fluorescence (HPLC-FL) detectors have been used. The results showed that total
      PAHs concentration varied between 1,945 ng g(-1) dry matter (DM) for primary
      sludges collected in March and 10,100 ng g(-1) DM for primary sludge collected in
      June. Generally, concentrations of PAHs were higher in compost and digested
      sludge than in fresh one. On the other hand, the highest concentration of PAHs
      were found on summer. This thing is associated to the traffic increase from
      inland zones to the coast (Jerez de la Frontera is very near to beaches).
      Finally, this paper present a comparative study of the American an European
      legislation concluding that the limits of concentrations established are not
      exceeded. In addition heavy metals were analysed. The origin of PAHs and heavy
      metals seems to be different.

PMID- 16405956
TI  - A study of silicon carbide synthesis from waste serpentine.
AB  - There are 60000 tons of serpentine wastes produced in year 2004 in Taiwan. This
      is due to the well-developed joints in the serpentine ore body as well as the
      stringent requirements of the particle size and chemical composition of
      serpentine by iron making company. The waste also creates considerable
      environmental problems. The purpose of this study is reutilization of waste
      serpentine to produce a high value silica powder after acid leaching. These
      siliceous microstructure products obtained from serpentine would be responsible
      for high reactivity and characteristic molecular sieving effect. In this study,
      the amorphous silica powder was then synthesized to silicon carbide with the
      C/SiO(2) molar ratio of 3. The experiment results show that silicon carbide can
      be synthesized in 1550 degrees C. The formed silicon carbide was whisker beta
      type SiC which can be used as raw materials for industry.

PMID- 16405955
TI  - Evaluating a drinking-water waste by-product as a novel sorbent for arsenic.
AB  - Arsenic (As) carcinogenicity to humans and other living organisms has promulgated
      extensive research on As treatment technologies with varying levels of success;
      generally, the most efficient methods come with a significantly higher cost
      burden and they usually perform better in removing As(V) than As(III) from
      solution. In the reported study, a novel sorbent, a waste by-product of the
      drinking-water treatment process, namely, drinking-water treatment residuals
      (WTRs) were evaluated for their ability to adsorb both As(V) and As(III).
      Drinking-WTRs can be obtained free-of-charge from drinking-water treatment
      plants, and they have been successfully used to reduce soluble phosphorus (P)
      concentrations in poorly P-sorbing soils. Phosphate and arsenate molecules have
      the same tetrahedral geometry, and they chemically behave in a similar manner. We
      hypothesized that the WTRs would be effective sorbents for both As(V) and As(III)
      species. Two WTRs (one Fe- and one Al-based) were used in batch experiments to
      optimize the maximum As(V) and As(III) sorption capacities, utilizing the effects
      of solid:solution ratios and reaction kinetics. Results showed that both WTRs
      exhibited high affinities for soluble As(V) and As(III), exhibiting Freundlich
      type adsorption with no obvious plateau after 2-d of reaction (15000 mg kg-1).
      The Al-WTR was highly effective in removing both As(V) and As(III), although
      As(III) removal was much slower. The Fe-WTR showed greater affinity for As(III)
      than for As(V) and reached As(III) sorption capacity levels similar to those
      obtained with the Al-WTR-As(V) system (15000 mg kg-1). Arsenic sorption kinetics
      were biphasic, similar to what has been observed with P sorption by the WTRs.
      Minimal (<3%) desorption of sorbed As(III) and As(V) was observed, using
      phosphate as the desorbing ligand. Dissolved Fe2+ concentrations measured during
      As(III) sorption were significantly correlated (r2=0.74, p<0.005) with the amount
      of As(III) sorbed by the Fe-WTR. Lack of correlation between Fe2+ in solution and
      sorbed As(V) (r2=0.2) suggests reductive dissolution of the Fe-WTR mediating
      As(III) sorption. Results show promising potential for the WTRs in irreversibly
      retaining As(V) and As(III) that should be further tested in field settings.

PMID- 16405957
TI  - Contaminant concentrations in breeding and non-breeding northern fulmars
      (Fulmarus glacialis L.) from the Canadian high arctic.
AB  - Persistent organic pollutants (POPs) were measured in livers of male and female
      northern fulmars (Fulmarus glacialis) shortly after egg-laying on northern Devon
      Island, NU, Canada. Breeding females had lower hepatic POPs (lipid normalised)
      than breeding males, but non-breeding males and females had similar
      concentrations. We suspect that breeding females are eliminating some of their
      POPs during egg formation. Concentrations of measured POPs were lower than those
      associated with avian health concerns, and there was no evidence that POPs in the
      birds were contributing to additional breeding stress.

PMID- 16405959
TI  - Bioconcentration of trichlorfon insecticide in pacu (Piaractus mesopotamicus).
AB  - Pacu (Piaractus mesopotamicus) is one of the most representative fish species of
      Brazilian fish culture, produced in most Brazilian States due to its importance
      for food diet and sport fishery. This research work investigated the
      bioconcentration of trichlorfon [phosphonic acid, (2,2,2-trichloro-1
      hydroxyethyl)-dimethyl ester] insecticide in pacu under fish ponds culture
      conditions and a first-order kinetic insecticide dissipation in the water.
      Trichlorfon was applied at a rate of 4.62 x 10(4) mg to each of three nurseries
      containing 4.2 x 10(5)l of water. The fish ponds were built on the soil and
      supported 60 young pacus fishes. The concentrations of trichlorfon fitted to an
      equivalent non-linear kinetic type model, allows estimate the values of
      trichlorfon concentration in the water and fishes. These estimations together
      with the bioconcentration factor determined in the fishes, allowed establishing
      theoretical reference limit values for human consumption of fishes produced under
      cultivation systems with trichlorfon. This information will contribute to enlarge
      the database on pesticide use in Brazilian commercial fish farming, especially
      about the use of trichlorfon as chemotherapy for the control of fish
      ectoparasites.

PMID- 16405958
TI  - Persistent organic pollutants in moss as bioindicators of atmospheric pollution
      in Singapore.
AB  - Moss samples were collected from the island of Singapore and analysed for a range
      of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs).
      Although all compounds analysed have been banned from use in Singapore, they were
      detected in all samples collected. Among the hexachlorocyclohexanes (HCH), beta
      HCH was the most dominant isomer, while trans-chlorane was found to be the most
      dominant cyclodiene pesticide. High levels (79.12 ng g(-1)) of PCBs were detected
      in mosses collected from a nearby island due to active accumulation of pollutants
      associated with boat emissions. Significant spatial variations in the levels of
      organic pollutants in Singapore were largely absent, indicating that air masses
      moving over the island deposit OCPs and PCBs in a uniform pattern. A comparison
      of moss pollutant levels with available data from Czech Republic showed that
      dichlorodiphenyldichloroethylene (p,p'-DDE), dichlorodiphenyltrichloroethane
      (p,p'-DDT) and PCB levels in Singapore are the highest. The presence of these
      compounds suggests that they are still used in the region and are environmentally
      recalcitrant.

PMID- 16405960
TI  - Smads oppose Hox transcriptional activities.
AB  - BMPs and Hox proteins play crucial roles in developmental processes. Beyond their
      mutual regulation of gene expression, little is known about the relations between
      their mechanisms of actions. Previously, we have shown that Hoxc8 acts as a
      downstream repressor in the BMP signaling pathway. Smad1 and Smad6 interact with
      Hoxc8 and regulate its repression activities. The Hox family contains 39 genes
      divided into 13 paralogs. In this report, we systemically examined the potential
      functions of all the paralogous Hox proteins as BMP downstream transcription
      factors. Representative Hox proteins from each paralog were tested. In the gel
      shift assay, we found that Smad1, Smad4, and Smad6 interacted with most of the
      Hox proteins in ways similar to their interactions with Hoxc8. The interactions
      were confirmed in mammalian cells. We also examined the effects of Smads on Hox
      induced transactivation. Particularly, we determined that for Hoxd10 as a
      transcriptional activator, both Smad1 and Smad6 opposed its activity. In
      addition, Smad6 also inhibited Hoxc8- and Hoxb7-induced osteoprotegerin (OPG)
      transactivation. Furthermore, Smad1 inhibited Hoxb4-mediated target gene Irx5
      expression during early Xenopus development. Our findings suggest that Hox
      proteins act as general downstream DNA-binding proteins in BMP signaling cascade
      and their transcriptional activities are regulated by Smads.

PMID- 16405961
TI  - Alterations in mitochondrial function, hydrogen peroxide release and oxidative
      damage in mouse hind-limb skeletal muscle during aging.
AB  - Mitochondrial function, hydrogen peroxide generation and oxidative damage were
      measured in hind-limb skeletal muscle from young (6-8 month) and old (27-29
      month) wildtype and heterozygous Mn-superoxide dismutase (MnSOD) knockout mice
      (Sod2(+/-)). The reduction in MnSOD activity in the Sod2(+/-) mice makes these
      mice a good model to examine the implications of life-long elevated endogenous
      mitochondrial oxidative stress on mitochondrial function. ATP production was
      reduced approximately 30% with age in skeletal muscle mitochondria isolated from
      wildtype mice, and reduced 40-45% in mitochondria from both young and old Sod2(+/
      ) mice compared to the young wildtype mice. Release of hydrogen peroxide from
      skeletal muscle mitochondria increased 40-50% with age in both wildtype and
      Sod2(+/-) but was not higher in mitochondria from Sod2(+/-) mice. Activities of
      electron transport Complexes I and V were decreased 25-30% in both young and old
      Sod2(+/-) mice compared to wildtype mice, and were 25-30% lower in mitochondria
      from old wildtype and old Sod2(+/-) mice. DNA oxidative damage (oxo8dG levels)
      increased more than 45% with age and over 130% in the young Sod2(+/-) mice
      compared to the wildtype mice. These data show that mitochondrial oxidative
      stress in mouse skeletal muscle is increased with age, leading to alterations in
      mitochondrial function. In addition, increased oxidative stress generated by
      reduced activity of MnSOD does not exacerbate these alterations during aging.

PMID- 16405963
TI  - Differential promoter usage of infA in response to cold shock in Escherichia
      coli.
AB  - Initiation factor 1 (IF1) is an essential protein in Escherichia coli involved in
      the initiation step of protein synthesis. The protein level of IF1 increases when
      E. coli cells are subjected to cold shock, however, it remains unclear as to how
      this increase occurs. The infA gene encoding IF1 contains two promoters, the
      distal P1 and the proximal P2 promoter. In this study, we found that infA mRNA
      was greatly increased, and that this increase resulted from transcriptional
      activation of P1, not P2, during cold shock although stability of transcripts
      from both promoters concomitantly increased.

PMID- 16405962
TI  - Impact of genetic variations in the WRN gene on age related pathologies and
      mortality.
AB  - Mutations in the WRN gene lead to the Werner syndrome (WS), which resembles
      premature aging. Here, we hypothesize that genetic variations in the WRN gene may
      also influence aging-trajectories in the population at large. To test this
      hypothesis, we assessed the impact of the i1-C/T, L1074F and C1367R polymorphisms
      in the WRN gene on the occurrence of cardiovascular pathologies, on cognitive
      performance and on the risks of all-cause, cardiovascular and cancer mortalities
      in the population-based Leiden 85-plus Study. This prospective follow-up study
      includes 1,245 participants aged 85 years and older, with a total follow-up of
      5,164 person-years. At baseline the risks of myocardial infarction, myocardial
      ischemia, intermittent claudication, arterial surgery and stroke dependent on the
      i1-C/T, L1074F and C1367R polymorphisms, did not vary between the different
      genotypes. Also no differences in cognitive functioning were observed, except for
      attention, where carriers of the 1367R allele performed worse compared to the
      1367C homozygotes (94.2 (4.35) versus 84.8 (1.84), p=0.04). Mortality risks,
      calculated separately for all SNPs, were similar between the different genotype
      carriers of the i1-C/T, L1074F and C1367R polymorphisms, showing no evidence of
      altered survival. In conclusion, the i1-C/T, L1074F and C1367R polymorphisms in
      the WRN gene do not influence the aging-trajectories and survival in the
      population at large.

PMID- 16405964
TI  - Inhibition of the ATPase activity of Escherichia coli ATP synthase by magnesium
      fluoride.
AB  - Inhibition of ATPase activity of Escherichia coli ATP synthase by magnesium
      fluoride (MgFx) was studied. Wild-type F(1)-ATPase was inhibited potently, albeit
      slowly, when incubated with MgCl(2), NaF, and NaADP. The combination of all three
      components was required. Reactivation of ATPase activity, after removal of
      unbound ligands, occurred with half-time of approximately 14 h at 22 degrees C
      and was quasi-irreversible at 4 degrees C. Mutant F(1)-ATPases, in which
      catalytic site residues involved in transition state formation were modified,
      were found to be resistant to inhibition by MgFx. The data demonstrate that MgFx
      in combination with MgADP behaves as a tight-binding transition state analog in
      E. coli ATP synthase.

PMID- 16405965
TI  - Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral
      replication.
AB  - Hepatitis C virus (HCV) is a positive-strand RNA virus that frequently causes
      persistent infection associated with severe liver disease. HCV nonstructural
      protein 5A (NS5A) is essential for viral replication. Here, the kinase Raf-1 was
      identified as a novel cellular binding partner of NS5A, binding to the C-terminal
      domain of NS5A. Raf-1 colocalizes with NS5A in the HCV replication complex. The
      interaction of NS5A with Raf-1 results in increased Raf-1 phosphorylation at
      serine 338. Integrity of Raf-1 is crucial for HCV replication: inhibition of Raf
      1 by the small-molecule inhibitor BAY43-9006 or downregulation of Raf-1 by siRNA
      attenuates viral replication.

PMID- 16405966
TI  - Thiorphan, tiopronin, and related analogs as substrates and inhibitors of
      peptidylglycine alpha-amidating monooxygenase (PAM).
AB  - Peptidyglycine alpha-amidating monooxygenase is a copper- and zinc-dependent,
      bifunctional enzyme that catalyzes the cleavage of glycine-extended peptides or N
      acylglycines to the corresponding amides and glyoxylate. This reaction is a key
      step in the biosynthesis of bioactive alpha-amidated peptides and, perhaps, the
      primary fatty acids amides also. Two clinically useful N-acylglycines are
      thiorphan and tiopronin, each with a thiol moiety attached to the acyl group. We
      report here that thiorphan and tiopronin are substrates for PAM, exhibiting
      relatively low K(M,app) and V(MAX,app) values. The low V(MAX,app) values result,
      most likely, from a decrease in active PAM.2Cu(II) as the enzyme competes
      ineffectively with thiorphan and tiopronin for free copper.

PMID- 16405967
TI  - The molecular basis of multidrug resistance in cancer: the early years of P
      glycoprotein research.
AB  - The discovery and characterization of P-glycoprotein, an energy-dependent
      multidrug efflux pump, as a mechanism of multidrug resistance in cancer is
      generally accepted as a significant contribution to the ongoing effort to end
      death and suffering from this disease. The historical reflections of Victor Ling
      and Michael Gottesman concerning the early years of this research highlight the
      important contributions of the multidisciplinary teams involved in these studies,
      and illustrate how technological developments in biochemistry and molecular and
      cell biology enabled this discovery.

PMID- 16405968
TI  - Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell
      regeneration.
AB  - Regenerating gene product (Reg) is induced in pancreatic beta-cells and acts as
      an autocrine/paracrine growth factor for regeneration via a cell surface Reg
      receptor. However, the manner by which Reg induces beta-cell regeneration was
      unknown. In the present study, we found that Reg increased phospho-ATF-2, which
      binds to -57 to -52 of the cyclin D1 gene to activate the promoter. The Reg/ATF-2
      induced cyclin D1 promoter activation was attenuated by PI(3)K inhibitors such as
      LY294002 and wortmannin. In Reg knockout mouse islets, the levels of phospho-ATF
      2, cyclin D1, and phospho-Rb were greatly decreased. These results indicate that
      the Reg-Reg receptor system stimulates the PI(3)K/ATF-2/cyclin D1 signaling
      pathway to induce beta-cell regeneration.

PMID- 16405970
TI  - A novel toxin from the venom of the scorpion Tityus trivittatus, is the first
      member of a new alpha-KTX subfamily.
AB  - The first example of a new sub-family of toxins (alpha-KTx20.1) from the scorpion
      Tityus trivittatus was purified, sequenced and characterized physiologically. It
      has 29 amino acid residues, three disulfide bridges assumed to adopt the cysteine
      stabilized alpha/beta scaffold with a pI value of 8.98. The sequence identities
      with all the other known alpha-KTx are less than 40%. Its effects were verified
      using seven different cloned K(+) channels (vertebrate Kv1.1-1.5, Shaker IR and
      hERG) expressed in Xenopus leavis oocytes. The toxin-induced effects show large
      differences among the different K(+) channels and a preference towards Kv1.3
      (EC50=7.9+/-1.4 nM).

PMID- 16405969
TI  - TbGPI16 is an essential component of GPI transamidase in Trypanosoma brucei.
AB  - Glycosylphosphatidylinositol (GPI) is widely used by eukaryotic cell surface
      proteins for membrane attachment. De novo synthesized GPI precursors are attached
      to proteins post-translationally by the enzyme complex, GPI transamidase.
      TbGPI16, a component of the trypanosome transamidase, shares similarity with
      human PIG-T. Here, we show that TbGPI16 is the orthologue of PIG-T and an
      essential component of GPI transamidase by creating a TbGPI16 knockout. TbGPI16
      forms a disulfide-linked complex with TbGPI8. A cysteine to serine mutant of
      TbGPI16 was unable to fully restore the surface expression of GPI-anchored
      proteins upon transfection into the knockout cells, indicating that its disulfide
      linkage with TbGPI8 is important for the full transamidase activity.

PMID- 16405972
TI  - Sources and trends of environmental mercury emissions in Asia.
AB  - This paper focuses on environmental mercury emissions in Asia and elaborates its
      probable trend in the future and associated implications given the anticipated
      socioeconomic outlook and other macro-environmental factors. Among the various
      regions, Asia has become the largest contributor of anthropogenic atmospheric Hg,
      responsible for over half of the global emission. In the next few decades, a
      significant increase in anthropogenic Hg emissions in Asia is likely owing to
      rapid economic and industrial development, unless drastic measures are taken. In
      particular, the dominance of Asia in some Hg-emitting industries, such as coal
      combustion, steel production and gold mining, provokes a serious environmental
      concern over their potential contributions of incidental Hg in the region.
      Moreover, the increasing prevalence of electrical and electronic manufacturing
      industry as a user and a contributor of Hg in Asia is also worrying.
      Specifically, disposal of obsolete electrical and electronic wastes represents a
      phenomenon increasingly encountered in Asia. In addition to escalating
      anthropogenic Hg emissions in Asia, associated environmental and health
      implications may also exacerbate in the region for the probable effects of a
      unique combination of climatic (e.g. subtropical climate), environmental (e.g.
      acid rain) and socioeconomic factors (e.g. high population density). Hence, much
      effort is still needed to understand the role of Asia in global Hg cycle and
      associated environmental and health effects in the region.

PMID- 16405971
TI  - Calcium ions are involved in the delay of plant cell cycle progression by abiotic
      stresses.
AB  - Higher plants respond to environmental stresses by a sequence of reactions which
      include the reduction of growth by affecting cell division. It has been shown
      that calcium ions plays a role as a second messenger in mediating various defence
      responses under environmental stresses. In this study, the role of calcium ions
      on cell cycle progression under abiotic stresses has been examined in tobacco BY
      2 suspension culture cells. Using synchronized BY-2 cells expressing the
      endogenous calcium sensor aequorin as experimental system, we could show that
      oxidative and hypoosmotic stress both induce an increase of intracellular calcium
      and cause a delay of the cell cycle. The inhibitory effect of these abiotic
      stress stimuli on cell cycle progression could be mimicked by increasing the
      intracellular calcium concentration via application of an external electrical
      field. Likewise, depletion of calcium ions in the culture medium suppressed the
      effect of the stimuli tested. These results demonstrate that calcium signalling
      is involved in the regulation of cell cycle progression in response to abiotic
      stress.

PMID- 16405973
TI  - Association between platelet P2Y12 haplotype and risk of cardiovascular events in
      chronic coronary disease.
AB  - INTRODUCTION: A positive association was recently described between P2Y12
      platelet receptor H1 and H2 haplotypes and peripheral artery disease. We tested
      the described P2Y12 receptor haplotypes in a group of patients with coronary
      artery disease. STUDY DESIGN AND METHODS: The P2Y12 platelet receptor H1 and H2
      haplotypes was tested in a group of 540 patients enrolled in the Medical,
      Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing
      treatments for patients with coronary artery disease (CAD) and preserved left
      ventricular function. After a 3-year follow-up period, the incidence of the
      composite end point of cardiac death, myocardial infarction, and refractory
      angina requiring revascularization was determined in the H1/H1, H1/H2 and H2/H2
      haplotype groups. We used Student's t-test and the chi-square test to analyze the
      differences among groups and Kaplan-Meier method to calculate survival curves.
      Risk was assessed with the use of a Cox proportional-hazards model. RESULTS: The
      frequency of haplotypes among studied patients were 410 (75.9%) H1/H1, 119
      (22.0%) H1/H2 and 11 (2.1%) H2/H2. The baseline clinical characteristics, mean
      clinical follow-up time and received treatment of each genotype group were
      similar. We did not disclose any association between haplotype groups regarding
      the incidence of any of the studied cardiovascular end-points. CONCLUSION: This
      is the first report studying the association of P2Y12 platelet receptor H1 and H2
      haplotype and cardiovascular events. Our findings do not provide evidence for a
      strong association between H1/H1 and H1/H2 haplotypes and a increased risk of
      cardiovascular events in a population with CAD. Future works should address the
      role of the H2/H2 haplotype as a genetic marker for cardiovascular events.

PMID- 16405974
TI  - Differences in platelet reactivity response to mental stress in syndrome X and
      coronary artery disease: a biased result only?

PMID- 16405975
TI  - Hemostatic activation in a chemically induced rat model of severe hemolysis and
      thrombosis.
AB  - INTRODUCTION: In hemolytic diseases such as sickle cell disease and beta
      thalassemia, the mechanisms of thrombosis are poorly understood, however
      erythrocyte/endothelium interactions are thought to play an important role.
      Appropriate animal models would increase our understanding of the pathophysiology
      of thrombosis and aid in the development of new therapeutic strategies. We
      previously reported that rats exposed to 2-butoxyethanol (2-BE) develop hemolysis
      and enhanced adherence of erythrocytes to the extracellular matrix, possibly
      secondary to the recruitment of cellular adhesion molecules at the
      erythrocyte/endothelium interface. METHODS: We exposed rats to 250 mg/kg/day of 2
      BE for 4 days, and collected blood for coagulation markers on each day. RESULTS:
      As previously observed, erythrocytes dropped precipitously (8.0 to
      1.8x10(6)/microl in 48 h), and diffuse microvascular thrombosis developed in the
      heart, lungs, liver, bones and eyes. Prothrombin times, activated partial
      thromboplastin times, fibrinogen, and antithrombin-III were unchanged between
      treated and control rats, indicating that hemostasis is largely unperturbed.
      However the thrombin-antithrombin III levels in the 2-BE treated rats for all
      days were 3-7 times greater than the control rats. The plasma intercellular
      adhesion molecule-1 (ICAM-1) levels of 2-BE treated animals were approximately
      twice that of the controls on days 2 and 3 and 1.5 times the controls on day 4
      (P<0.05). CONCLUSION: Our findings are consistent with the observations of
      increased erythrocyte aggregation, increased erythrocyte/endothelium interaction,
      and increased plasma ICAM-1 levels observed in sickle cell disease and beta
      thalassemia patients. This model may be useful for studying therapeutic agents
      that disrupt erythrocyte/endothelium interactions.

PMID- 16405976
TI  - Long-term outcomes of vaginal reconstruction with and without amnion grafts.

PMID- 16405977
TI  - Pulsed electrochemical detection of orotic acid by an activated potential
      waveform at a gold working electrode following anion-exchange chromatography.
AB  - The application of activated pulsed amperometric detection (APAD) for the
      determination of orotic acid (OrA) in real samples at a gold working electrode in
      alkaline solutions, in combination with anion-exchange chromatography, is
      reported. Such an activated potential waveform was designed with an initial step
      that involves the formation of redox active species (e.g., adsorbed AuOH/AuO),
      which in turn is halted upon lowering the applied potential at the detection
      value while the adsorbed gold hydroxide/oxide species are still catalytically
      active. A direct comparison between the activated potential waveform and the more
      commonly used pulsed amperometric detection showed roughly a 20-fold increase in
      sensitivity. The chromatographic separation of OrA was accomplished by using a
      microbore anion-exchange column eluted with an isocratic mobile phase composed of
      100 mM NaOH+40 mM NaNO(3). Orotic acid was determined at the concentration ranges
      of 0.2-30 microM (r=0.9997) with an absolute detection limit of 80 pg (10 microL
      injected). The levels of OrA in cows' milk samples evaluated by standard
      additions, using 5-aminoorotic acid as an internal standard, ranged from 56 to
      126 mg/L. Lower levels were found in raw sheep's milk (<20 mg/L). The assay is
      shown to be very useful in clinical investigations where relatively high levels
      of OrA in human urine are correlated to metabolic diseases.

PMID- 16405978
TI  - Identification of tanshinone IIA metabolites in rat liver microsomes by liquid
      chromatography-tandem mass spectrometry.
AB  - Tanshinone IIA, the major component extracted from Radix salvia miltiorrhiza, has
      been observed to possess various kinds of pharmacological activities including
      antioxidant, prevention of angina pectoris and myocardial infarction and
      anticancer. Tanshinone IIA was incubated with rat liver microsomes and the
      resulting metabolites were identified by liquid chromatography/tandem mass
      spectrometry. The results showed the formation of three main hydroxyl
      metabolites. The three hydroxyl metabolites of tanshinone IIA were proved to be
      tanshinone IIB, hydroxytanshinone IIA and przewaquinone A by comparing the tandem
      mass spectra and the chromatographic retention time with that of the respective
      authentic compounds. Tanshinone IIB, hydroxytanshinone IIA and przewaquinone A
      are all the chemical components of total tanshinones. It was reasonable to
      presume that the three hydroxy metabolites of tanshinone IIA were
      pharmacologically active the same as tanshinone IIA and the total tanshinones.

PMID- 16405979
TI  - Quantification of chloroanisoles in cork using headspace solid-phase
      microextraction and gas chromatography with electron capture detection.
AB  - Chloroanisoles can migrate from the cork stopper in wine bottles to the wine and
      give it a musty taint so it is important to find a method by which they can be
      determined. The aim of this paper is to develop a method for quantifying 2,4
      dichloroanisole, 2,6-dichloroanisole, 2,4,6-trichloroanisole, 2,3,4,6
      tetrachloroanisole and 2,3,4,5,6-pentachloroanisole in cork using headspace solid
      phase microextraction and gas chromatography with electron capture detection.
      After we had prepared the cork standards that were so essential to the work we
      optimised the parameters that most influence headspace solid-phase
      microextraction: fibre coating, vial volume, cork, kind and volume of solvent to
      help the extraction, extraction temperature and time, ionic strength and
      stirring. The method quantifies the total amount of chloroanisoles in cork
      stoppers (natural, agglomerated, agglomerated with disks and sparkling wine
      stoppers), at suitable concentrations so that the capacity of these compounds to
      give wine a musty taint can be evaluated. The quantification limits are: 2,6
      dichloroanisole (8.6 ng/g), 2,4,6-trichloroanisole (0.8 ng/g), 2,4
      dichloroanisole (3.5 ng/g), 2,3,4,6-tetrachloroanisole (0.6 ng/g), 2,3,4,5,6
      pentachloroanisole (0.8 ng/g). The other quality parameters are: recoveries (90.3
      105.8%), repeatability (4-13% (RSD expressed)) and intermediate precision (5-14%
      (RSD expressed)).

PMID- 16405980
TI  - Determination of sugar compounds in atmospheric aerosols by liquid chromatography
      combined with positive electrospray ionization mass spectrometry.
AB  - We here report a method for the determination of sugar compounds of known
      presence in atmospheric aerosols using liquid chromatography (LC) combined with
      positive electrospray ionization mass spectrometry (MS). The target analytes
      include C(3)-C(6) monosaccharide alcohols (glycerol, erythritol, xylitol,
      mannitol), C(5)-C(6) monosaccharides (xylose, glucose, and levoglucosan), a
      disaccharide (sucrose), and a trisaccharide (melezitose). A mobile phase
      consisting of 20% 10 mM aqueous ammonium acetate, 8% methanol, and 72% water was
      found to provide abundant [M+NH(4)](+) adduct ions when coupled with electrospray
      ionization. Use of a polymer-based amino analytical column resolved the target
      compounds from the bulk solvent and provided limited separation among the target
      compounds. The target analytes were quantified using their [M+NH(4)](+) ions.
      Sample pretreatment was greatly simplified in comparison with the more commonly
      used gas chromatographic methods. It involved extraction of aerosol filters in
      methanol, evaporation of the solvent, and reconstitution with 5 mM ammonium
      acetate in water prior to the LC-MS analysis. The analyte recoveries were
      measured at the levels of 100, 500 and 1000 microg/L to be in the range of 78
      102%, 94-112%, and 92-110%, respectively. The detection limits were lower than 10
      pmol/injection for the tested target compounds except for xylose. Xylose had a
      detection limit of 95 pmol/injection. The method was applied to analyze 30
      atmospheric aerosol samples to demonstrate its feasibility. The LC-MS method made
      possible the detection of trisaccharides as aerosol constituents for the first
      time.

PMID- 16405981
TI  - Selective antagonist at D3 receptors, but not non-selective partial agonists,
      influences the expression of cocaine-induced conditioned place preference in free
      feeding rats.
AB  - The non-selective dopamine (DA) D(3) partial agonist BP 897 influenced rats'
      seeking behavior induced by cocaine-associated cues but there are contradictions
      about its ability to modulate cocaine-induced conditioned place preference (CPP),
      and mechanisms involved. We therefore re-evaluated its activity on both
      acquisition and expression of these behaviors, taking into consideration the
      actual brain concentrations of unchanged drug and its potential active metabolite
      1-(2-methoxyphenyl)-piperazine (oOCH(3)PP), as well as its negative motivational
      properties. BP 897 induced conditioned place aversion (CPA) at 3 mg/kg, but not
      at 0.3 and 1 mg/kg. However, in this range of amply spaced doses BP 897 did not
      affect the acquisition and expression of cocaine (10 mg/kg i.p.) CPP in rats,
      although its brain concentrations were well above those affecting in vitro D(3)
      receptors. Concentrations of oOCH(3)PP were below the limits of quantification of
      the analytical procedure. As concerns the expression behavior, its structurally
      and pharmacologically related derivative N-[4-[4-(2-methoxyphenyl)piperazin-1
      yl]butyl]benzo[b]furan-2-carboxamide (1 and 3 mg/kg, i.p.) also had no such
      effect. By contrast, the selective D(3) receptor antagonist SB-277011-A (3 mg/kg,
      i.p.) antagonized the expression of cocaine-induced CPP, supporting the
      suggestion that "full" antagonist activity at D(3) receptors is necessary to
      prevent 10 mg/kg cocaine-induced place conditioning in free-feeding rats.

PMID- 16405982
TI  - Reflections on trust and health services utilization.

PMID- 16405983
TI  - Disparities among the disadvantaged: variation in lipid management in the Ohio
      Medicaid program.
AB  - BACKGROUND: Racial disparities exist in cardiovascular disease (CVD) prevention,
      but other non-clinical factors may influence treatment, further exacerbating
      disparities. METHODS: Using Ohio Medicaid data from 1992 to 1999, we identified a
      sample of 19,106 individuals with CVD-related diagnoses or procedures. A review
      of pharmacy claims identified previous, new, and long-term users of lipid
      lowering agents, including statins, fibrates, and bile sequestrants. RESULTS:
      3,934 (20.6%) Medicaid beneficiaries used lipid-lowering medications previously,
      1,598 (10.5%) filed new claims, and 2,998 of 5,532 (54.2%) previous or new users
      filed >or=6 claims for refills. Minority adults <or=60 years were least likely to
      have been previous users (0.80 [0.67, 0.96]), new users (0.75 [0.58, 0.98]), or
      to use lipid-lowering agents long-term (0.65 [0.49, 0.84]). CONCLUSIONS: Targeted
      efforts to enhance younger minority adults' receipt and long-term use of lipid
      lowering agents may reduce risks for subsequent morbidity and mortality related
      to CVD.

PMID- 16405984
TI  - Temperature effects upon aqueous micellar-assisted decarboxylation of 6
      nitrobenzisoxazole-3-carboxylate and its 5-methyl derivative.
AB  - An investigation of temperature effects upon first-order rate constants in the
      micellar pseudophase for decarboxylation of 6-nitrobenzisoxazole-3-carboxylate (6
      NBIC) and its 5-methyl derivative (6-NBIC-5-Me) was carried out. Surfactants used
      were cationic cetyltrialkylammonium bromide with alkyl = methyl (CTABr), ethyl
      (CTEABr), n-propyl (CTPABr), and n-butyl (CTBABr). The investigation shows that
      micelles speed up reactions by decreasing enthalpies of activation. Increase in
      head group bulk further speeds reactions still by a small decrease in the
      enthalpies, for both substrates. Values of DeltaH# and DeltaS# for 6-NBIC in the
      various surfactants give linear isokinetic plot, with CTBABr as outlier.

PMID- 16405985
TI  - Phonological encoding in the silent speech of persons who stutter.
AB  - The purpose of the present study was to investigate the role of phonological
      encoding in the silent speech of persons who stutter (PWS) and persons who do not
      stutter (PNS). Participants were 10 PWS (M=30.4 years, S.D.=7.8), matched in age,
      gender, and handedness with 11 PNS (M=30.1 years, S.D.=7.8). Each participant
      performed five tasks: a familiarization task, an overt picture naming task, a
      task of self-monitoring target phonemes during concurrent silent picture naming,
      a task of monitoring target pure tones in aurally presented tonal sequences, and
      a simple motor task requiring finger button clicks in response to an auditory
      tone. Results indicated that PWS were significantly slower in phoneme monitoring
      compared to PNS. No significant between-group differences were present for
      response speed during the auditory monitoring, picture naming or simple motor
      tasks, nor did the two groups differ for percent errors in any of the
      experimental tasks. The findings were interpreted to suggest a specific
      deficiency at the level of phonological monitoring, rather than a general
      monitoring, reaction time or auditory monitoring deficit in PWS. EDUCATIONAL
      OBJECTIVES: As a result of this activity, the participant should: (1) identify
      and assess the literature on phonological encoding skills in PWS, (2) enumerate
      and evaluate some major psycholinguistic theories of stuttering, and (3) describe
      the mechanism by which defective phonological encoding can disrupt fluent speech
      production.

PMID- 16405986
TI  - The safety of nickel containing dental alloys.
AB  - Nickel is a constituent of many dental alloys. This paper reviews mainly papers
      published after 1985 with regards to biological reactions to nickel in dentistry.
      Nickel is an allergen, but there is no evidence that individual patients are at a
      significant risk of developing sensitivity solely due to contact with nickel
      containing dental appliances and restorations. Hypersensitivity reactions to
      nickel are only likely to occur with prior sensitization from non-dental contacts
      and even these are rare. Clinical evidence has been presented to show that small
      doses of nickel, e.g. from dental appliances, may induce tolerance to this
      allergen. The papers reviewed report low rates of release of nickel from dental
      alloys. Some nickel compounds, which are mildly cytotoxic, have been implicated
      as carcinogens by inhalation in industrial settings, but these compounds are not
      present in dentistry-related operations, including dental technology procedures.
      Nickel-containing alloys and compounds have not been associated with increased
      cancer risk by oral or dermal routes of exposure. It is concluded that, subject
      to use according to established techniques, nickel-containing dental alloys do
      not pose a risk to patients or members of the dental team.

PMID- 16405987
TI  - Water sorption/solubility of dental adhesive resins.
AB  - OBJECTIVES: This study evaluated the water sorption, solubility and kinetics of
      water diffusion in commercial and experimental resins that are formulated to be
      used as dentin and enamel bonding agents. METHODS: Four commercial adhesives were
      selected along with their solvent-monomer combination: the bonding resins were of
      Adper Scotchbond Multi-Purpose (MP) and Clearfil SE Bond (SE) systems, and the
      "one-bottle" systems, Adper Single Bond (SB) and Excite (EX). Five experimental
      methacrylate-based resins of known hydrophilicities (R1, R2, R3, R4 and R5) were
      used as reference materials. Specimen disks were prepared by dispensing the
      uncured resin into a mould (5.8mm x 0.8mm). After desiccation, the cured
      specimens were weighed and then stored in distilled water for evaluation of the
      water diffusion kinetics over a 28-day period. RESULTS: Resin composition and
      hydrophilicity (ranked by their Hoy's solubility parameters) influenced water
      sorption, solubility and water diffusion in both commercial and experimental
      dental resins. The most hydrophilic experimental resin, R5, showed the highest
      water sorption, solubility and water diffusion coefficient. Among the commercial
      adhesives, the solvated systems, SB and EX, showed water sorption, solubility and
      water diffusion coefficients significantly greater than those observed for the
      non-solvated systems, MP and SE (p<0.05). In general, the extent and rate of
      water sorption increased with the hydrophilicity of the resin blends.
      SIGNIFICANCE: The extensive amount of water sorption in the current hydrophilic
      dental resins is a cause of concern. This may affect the mechanical stability of
      these resins and favor the rapid and catastrophic degradation of resin-dentin
      bonds.

PMID- 16405988
TI  - Effects of moisture degree and rubbing action on the immediate resin-dentin bond
      strength.
AB  - OBJECTIVES: To compare the effects of moisture and rubbing action on the
      microtensile bond strength (BS) of an ethanol/water-based (Single Bond [SB]) and
      an acetone-based system (One-Step [OS]) to dentin. METHODS: On 60 human molars, a
      flat superficial dentin surface was exposed by wet abrasion. Two coats of the
      adhesives were applied on either a dry (D) or rewetted surface (W), under no
      rubbing action (NRA), slight (SRA) or vigorous rubbing action (VRA). After light
      curing (600 mW/cm2/10 s), composite build-ups were constructed incrementally and
      specimens were stored in water (37 degrees C/24 h). They were longitudinally
      sectioned in the "x" and "y" directions to obtain bonded sticks (0.8 mm2) to be
      tested in tension at 0.5 mm/min. Resultant BS was expressed as an index that
      includes bond strength values of the different fracture patterns and the
      specimens that failed during preparation for testing. The data were analyzed by a
      three-way ANOVA and Tukey's multiple comparison tests (95%). RESULTS: The
      interactions moisture/agitation and adhesive/agitation were statistically
      significant (p < 0.05). In D groups, the highest BS was obtained under VRA (37.11
      +/- 7.3). In W groups, the BS at SRA (41.82 +/- 8.4) and VRA (38.89 +/- 8.2) were
      similar. For SB system, the SRA (33.6 +/- 8.3) and VRA groups (41.26 +/- 5.9)
      yielded similar BS while for OS the VRA was essential to reach high BS (34.2 +/-
      8.4). SIGNIFICANCE: High BS to dentin can be obtained, under dry conditions, when
      ethanol/water and acetone-based systems, are vigorously agitated in the surface.
      On wet dentin, slight agitation seems to be enough to provide high BS to dentin.

PMID- 16405989
TI  - Transfer and fate of seminal fluid molecules in the beetle, Diaprepes
      abbreviatus: implications for the reproductive biology of a pest species.
AB  - Molecules transferred from males to females via seminal fluids are important to
      the study of insect reproduction because they affect female physiology,
      reproductive behavior, and longevity. These molecules (seminal fluid molecules or
      SFMs) interest applied entomologists because of their potential use in insect
      control. SFMs are also interesting because of their relatively rapid evolution
      and important role in post-mating sexual selection. We studied SFMs in Diaprepes
      abbreviatus, a major pest of numerous plant species of economic importance. Using
      radiolabeled-methionine (35S), we found that D. abbreviatus males synthesized
      proteins de novo in their reproductive tissues after mating. Males that were fed
      radiolabeled methionine transferred radioactivity to females beginning within the
      first 10 min of mating. Male-derived substances are absorbed from the female's
      reproductive tract into the hemolymph and circulated throughout the body, but are
      found primarily in the eggs and ovaries. As a result, SFMs may be a useful means
      of both horizontal (to mates) and vertical transfer (to offspring) of control
      agents between conspecifics.

PMID- 16405990
TI  - [Paracolostomal hernia].
AB  - While relatively common, parastomal hernias are often well tolerated. The
      decision to operate and the choice of surgical technique should be well discussed
      taking into account the controversial results of the literature. We describe in
      the present article the repair techniques with stoma transposition.

PMID- 16405991
TI  - Preparation and hydrolytic degradation of semi-interpenetrating networks of
      poly(3-hydroxyundecenoate) and poly(lactide-co-glycolide).
AB  - Semi-interpenetrating networks (semi-IPNs), where poly(lactide-co-glycolide)
      (PLGA) molecules were entrapped in the crosslinked matrices of poly(3
      hydroxyundecenoate) (PHU), were prepared by irradiating homogeneous solutions of
      PHU and PLGA in chloroform with UV light. Attenuated total reflectance infrared
      spectroscopy showed that the PLGA chains were entrapped in PHU networks. The semi
      IPNs showed enhanced mechanical strength as the PLGA content increased. The semi
      IPNs were incubated at 37 degrees C in a 0.01N NaOH solution, and the extent of
      hydrolytic degradation was investigated by monitoring changes in various
      parameters such as water uptake, pH, mass, and morphology. Hydrolysis of semi
      IPNs were significantly affected by the presence of PLGA. A semi-IPN prepared
      from a 9:1 (by weight) mixture of PHU and PLGA lost 25% of its original weight in
      12 weeks while a PHU sample containing no PLGA lost only 5% of its weight during
      the same period under identical conditions. The hydrolysis was most likely
      accelerated when the pH of the medium was lowered by the hydrolyzed products of
      PLGA, 2-hydroxyalkanoic acids. These results showed that hydrolysis of PHA could
      be enhanced by incorporating a second component that lowered the pH of the
      hydrolysis system.

PMID- 16405992
TI  - Surface energy components of a dye-ligand immobilized pHEMA membranes: effects of
      their molecular attracting forces for non-covalent interactions with IgG and HSA
      in aqueous media.
AB  - In the present paper, we report the study of the adsorption behaviour of human
      immunoglobulin G (IgG), human serum albumin (HSA) and polyethylenimine (PEI) onto
      surfaces of Procion Green HE-4BD (PG) immobilized poly(hydroxyethylmethacrylate)
      (pHEMA) membranes. The adsorption behaviour of the IgG and HSA onto surfaces of
      the PG-PEI complexed membrane was also studied. Surface wettability and
      hydrophilicity of all the membranes were investigated by static contact angle
      measurements. The measurements of the contact angle to various test liquids,
      i.e., water, glycerol, formamide, diiodomethane (DIM) and ethylene glycol on the
      investigated membranes were made by sessile drop method. In accordance to the
      Young equation, the smaller the surface tension of the test liquid, the smaller
      becomes the contact angles measured on all the investigated membranes surfaces.
      The highest contact angles were obtained with water, whereas ethylene glycol gave
      the lowest contact angles for all the tested membranes. Component and parameters
      of the surface free energy of all the investigated membranes were calculated from
      measured contact angle values using two methods (the geometric mean by Fowkes and
      acid-base by van Oss). HSA adsorption was enhanced after complexation of PEI with
      the immobilized dye-ligand. The adsorption of proteins and PEI significantly
      changed both the contact angles and component of surface free energies of the
      investigated membranes.

PMID- 16405993
TI  - Purification of the YadA membrane anchor for secondary structure analysis and
      crystallization.
AB  - Non-fimbrial adhesins, such as Yersinia YadA, Moraxella UspA1 and A2, Haemophilus
      Hia and Hsf, or Bartonella BadA, represent an important class of molecules by
      which pathogenic proteobacteria adhere to their hosts. They form trimeric surface
      structures with a head-rod-anchor architecture. Whereas their head and rod
      domains may be of heterologous origin, their anchor domains are homologous and
      display the properties of autotransporters. Conflicting topology models exist for
      these membrane anchors. Here, we describe the expression and purification of the
      membrane anchor of YadA from Yersinia enterocolitica for structural biology
      experiments. We expressed YadA-M in the Escherichia coli outer membrane. After
      solubilization and purification, it is a trimer of extreme stability. Using
      protein FTIR and secondary structure analysis, we show that the anchor is a beta
      barrel, but contains a helical part at its N-terminus. We have crystallized the
      protein under various conditions and present X-ray data to 3.8 A resolution.

PMID- 16405994
TI  - Preparation and characterization of biocompatible polyelectrolyte complex
      multilayer of hyaluronic acid and poly-L-lysine.
AB  - A novel biocompatible polyelectrolyte complex multilayer (PECML) was successfully
      prepared using hyaluronic acid (HA) and poly-l-lysine (PLL). The formation of
      PECML through the electrostatic interaction of HA as a polyanion and PLL as a
      polycation was confirmed by contact angle measurement, ESCA analysis and HA
      content analysis. According to the Carbazole assay, HA content increased rapidly
      up to eight cycles for HA/PLL deposition and then slightly increased with an
      increasing number of deposition cycle. In vitro release of PLL from the PECML
      continued up to 4 days exhibiting different release profiles depending on the
      outer layer of PECML. This result provides evidence for PLL diffusion throughout
      PECML of HA and PLL during the multilayer buildup. About 25% of HA remained on
      the cover glass after the in vitro release test for 7 days. From the results, we
      confirmed that PECML of HA and PLL could remain at least partially on the
      chitosan-coated cover glass for 7 days. The surface modification with PECML
      resulted in drastically reduced peripheral blood mononuclear cell (PBMC)
      attachment according to the lactate dehydrogenase assay for cell counting. This
      nano-scale control of material deposition may be successfully applied for surface
      modification of various biomaterials.

PMID- 16405995
TI  - Fiber molecular model of atelocollagen-small interfering RNA (siRNA) complex.
AB  - Previously we represented molecular model of collagen triple helix-DNA double
      helix complex [G.M. Mrevlishvili, D.V. Svintradze, Int. J. Macromol. 36 (2005)
      324-326; G.M. Mrevlishvili, D.V. Svintradze, Int. J. Macromol. 35 (2005) 243
      245]. We also proved that during the complex formation hydration of triple helix
      destroys and forms new water bridges maintaining the complex nano-structure. In
      this paper we demonstrate that small interfering RNA binds to atelocollagen
      directly to form siRNA-atelocollagen fiber complex.

PMID- 16405996
TI  - Solution structure of the Vts1 SAM domain in the presence of RNA.
AB  - The yeast Vts1 SAM (sterile alpha motif) domain is a member of a new class of SAM
      domains that specifically bind RNA. To elucidate the structural basis for RNA
      binding, the solution structure of the Vts1 SAM domain, in the presence of a
      specific target RNA, has been solved by multidimensional heteronuclear NMR
      spectroscopy. The Vts1 SAM domain retains the "core" five-helix-bundle
      architecture of traditional SAM domains, but has additional short helices at N
      and C termini, comprising a small substructure that caps the core helices. The
      RNA-binding surface of Vts1, determined by chemical shift perturbation, maps near
      the ends of three of the core helices, in agreement with mutational data and the
      electrostatic properties of the molecule. These results provide a structural
      basis for the versatility of the SAM domain in protein and RNA-recognition.

PMID- 16405997
TI  - Induced fit and "lock and key" recognition of 5S RNA by zinc fingers of
      transcription factor IIIA.
AB  - Transcription factor IIIA (TFIIIA) is a Cys2His2 zinc finger protein that
      regulates expression of the 5 S ribosomal RNA gene by binding specifically to the
      internal control element. TFIIIA also functions in transport and storage of 5 S
      RNA by binding directly to the RNA transcript. To obtain insights into the
      mechanism by which TFIIIA recognizes 5 S RNA, we determined the solution
      structure of the middle three zinc fingers bound to the central core of 5 S RNA.
      Finger 4 utilizes "lock and key" recognition to bind in the widened major groove
      of the pre-structured RNA loop E motif. This interaction is mediated by direct
      hydrogen bonding interactions with bases. In contrast, recognition of loop A, a
      flexible junction of three helices, occurs by an induced fit mechanism that
      involves reorganization of the conserved CAUA motif and structuring of the finger
      5-finger 6 interface to form a complementary RNA binding surface.

PMID- 16405998
TI  - Functional interplay between the jaw domain of bacterial RNA polymerase and
      allele-specific residues in the product RNA-binding pocket.
AB  - Bacterial RNA polymerase (RNAP) is a complex molecular machine in which the
      network of interacting parts and their movements, including contacts to nascent
      RNA and the DNA template, are at best partially understood. The jaw domain is a
      part of RNAP that makes a key contact to duplex DNA as it enters the enzyme from
      downstream and also contacts two other parts of RNAP, the trigger loop, which
      lies in the RNAP secondary channel, and a sequence insertion in the Escherichia
      coli RNAP trigger loop that forms an external domain and also contacts downstream
      DNA. Deletion of the jaw domain causes defects in transcriptional pausing and in
      bacterial growth. We report here that these defects can be partially corrected by
      a limited set of substitutions in a distant part of RNAP, the product RNA-binding
      pocket. The product RNA-binding pocket binds nascent RNA upstream of the active
      site and is the binding site for the RNAP inhibitor rifampicin when RNA is
      absent. These substitutions have little effect on transcript elongation between
      pause sites and actually exacerbate jaw-deletion defects in transcription
      initiation, suggesting that the pausing defects may be principally responsible
      for the in vivo phenotype of the jaw deletion. We suggest that the counteracting
      effects on pausing of the alterations in the jaw and the product RNA binding site
      may be mediated either by effects on translocation or via allosteric
      communication to the RNAP active site.

PMID- 16405999
TI  - Lipid composition determines interaction of liposome membranes with Pluronic L61.
AB  - Triblock copolymers of ethylene oxide (EO) and propylene oxide (PO) of
      EO(n/2)PO(m)EO(n/2) type (Pluronics) demonstrate a variety of biological effects
      that are mainly due to their interaction with cell membranes. Previously, we have
      shown that Pluronics can bind to artificial lipid membranes and enhance
      accumulation of the anti-tumor drug doxorubicin (DOX) inside the pH-gradient
      liposomes and transmembrane migration (flip-flop) of NBD-labeled
      phosphatidylethanolamine in the liposomes composed from one component-lecithin.
      Here, we describe the effects caused by insertion of other natural lipids in
      lecithin liposomes and the significance of the lipid composition for interaction
      of Pluronic L61 with the membrane. We used binary liposomes consisting of
      lecithin and one of the following lipids: cholesterol, phosphatidylethanolamine,
      ganglioside GM1, sphingomyelin, cardiolipin or phosphatidic acid. The influence
      of the additives on (1) membrane microviscosity; (2) binding of Pluronic L61; (3)
      the copolymer effect on lipid flip-flop and membrane permeability towards DOX was
      studied. The results showed that insertion of sphingomyelin and cardiolipin did
      not influence membrane microviscosity and effects of Pluronic on the membrane
      permeability. Addition of phosphatidic acid led to a decrease in microviscosity
      of the bilayer and provoked its destabilization by the copolymer. On the
      contrary, cholesterol increased microviscosity of the membrane and decreased
      binding of Pluronic and its capacity to enhance flip-flop and DOX accumulation.
      Analogous tendencies were revealed upon incorporation of egg
      phosphatidylethanolamine or bovine brain ganglioside GM1. Thus, a reverse
      dependence between the microviscosity of membranes and their sensitivity to
      Pluronic effects was demonstrated. The described data may be relevant to
      mechanisms of Pluronic L61 interaction with normal and tumor cells.

PMID- 16406000
TI  - Interaction of human valve interstitial cells with collagen matrices manufactured
      using rapid prototyping.
AB  - Rapid prototyping is a novel process for the production of scaffolds of
      predetermined size and three-dimensional shape. The aim of the study was to
      determine the feasibility of this technology for producing scaffolds for tissue
      engineering an aortic valve and the optimal concentration of collagen processed
      in this manner that would maintain viability and promote proliferation of human
      valve interstitial cells. Scaffolds of 1%, 2% and 5% w/v bovine type-I collagen
      were manufactured using rapid prototyping. Valve interstitial cells isolated from
      three human aortic valves were seeded on the scaffolds and cultured for up to 4
      weeks. Cell viability was assessed using the CellTiter 96 Aq(ueous) One Solution
      Cell Proliferation Assay and cell death by lactate dehydrogenase (LDH)
      measurement. Valve interstitial cells remained viable and proliferated within the
      collagen scaffolds. Cells consistently proliferated to a greater extent on 1%
      collagen scaffolds rather than either 2% or 5% collagen and after 4 weeks reached
      212+/-33.1%, 139+/-25.9% and 129+/-38.3% (mean+/-SD) of their initial seeding
      density on 1%, 2% and 5% collagen scaffolds, respectively. LDH analysis
      demonstrated that there was minimal cell death indicating that the collagen
      scaffold was not toxic to human valve interstitial cells. Rapid prototyping
      provides a route to optimize biological scaffold designs for tissue engineering
      cardiac valves. This technology has the versatility to create scaffolds that are
      compatible with the specific needs of the valve interstitial cells and should
      enhance cell viability, proliferation and function.

PMID- 16406001
TI  - Stabilization of inhomogeneous patterns in a diffusion-reaction system under
      structural and parametric uncertainties.
AB  - Many phenomena such as neuron firing in the brain, the travelling waves which
      produce the heartbeat, arrythmia and fibrillation in the heart, catalytic
      reactions or cellular organization activities, among others, can be described by
      a unifying paradigm based on a class of nonlinear reaction-diffusion mechanisms.
      The FitzHugh-Nagumo (FHN) model is a simplified version of such class which is
      known to capture most of the qualitative dynamic features found in the
      spatiotemporal signals. In this paper, we take advantage of the dissipative
      nature of diffusion-reaction systems and results in finite dimensional nonlinear
      control theory to develop a class of nonlinear feedback controllers which is able
      to ensure stabilization of moving fronts for the FHN system, despite structural
      or parametric uncertainty. In the context of heart or neuron activity, this class
      of control laws is expected to prevent cardiac or neurological disorders
      connected with spatiotemporal wave disruptions. In the same way, biochemical or
      cellular organization related with certain functional aspects of life could also
      be influenced or controlled by the same feedback logic. The stability and
      robustness properties of the controller will be proved theoretically and
      illustrated on simulation experiments.

PMID- 16406002
TI  - Neuroprotective role for carbonyl reductase?
AB  - Oxidative stress is increasingly implicated in neurodegenerative disorders
      including Alzheimer's, Parkinson's, Huntington's, and Creutzfeld-Jakob diseases
      or amyotrophic lateral sclerosis. Reactive oxygen species seem to play a
      significant role in neuronal cell death in that they generate reactive aldehydes
      from membrane lipid peroxidation. Several neuronal diseases are associated with
      increased accumulation of abnormal protein adducts of reactive aldehydes, which
      mediate oxidative stress-linked pathological events, including cellular growth
      inhibition and apoptosis induction. Combining findings on neurodegeneration and
      oxidative stress in Drosophila with studies on the metabolic characteristics of
      the human enzyme carbonyl reductase (CR), it is clear now that CR has a potential
      physiological role for neuroprotection in humans. Several lines of evidence
      suggest that CR represents a significant pathway for the detoxification of
      reactive aldehydes derived from lipid peroxidation and that CR in humans is
      essential for neuronal cell survival and to confer protection against oxidative
      stress-induced brain degeneration.

PMID- 16406003
TI  - Stereology and the placenta: where's the point? -- a review.
AB  - The value of stereology for describing the three-dimensional (3D) structural
      composition and spatial arrangement of biological specimens from essentially two
      dimensional (2D) thin sections is indisputable. By allowing economical
      quantitation of microscopical sections, stereology facilitates interpretations of
      normal and perturbed structure from the whole organ down to the subcellular
      levels. It incorporates the essential features of all sound study designs: (i)
      randomised sampling which is efficient and unbiased, and (ii) estimation tools
      which are simple, precise and unbiased or minimally biased. With these sampling
      and estimation tools, stereology offers a sure and safe option for characterising
      the total volumes, surfaces and lengths of placental compartments, the total
      numbers and mean sizes of nuclei or cells, and the spatial arrangements of
      tissues or intracellular ingredients. This review identifies the basic features
      of the stereological approach before indicating several ways in which stereology
      has been used to aid the description and interpretation of placental functional
      morphology from the whole organ to the molecular level. Examples include
      diffusive transport, villous growth, fetoplacental angiogenesis, trophoblast
      turnover, arterial vascular remodelling and high-resolution immuno-localization
      studies.

PMID- 16406004
TI  - Comparative placentation: some interesting modifications for histotrophic
      nutrition -- a review.
AB  - In considering the diversity of Eutherian mammalian placental structure, it is
      helpful to keep in mind that both phylogenetically and ontogenetically a
      functional yolk sac placenta precedes development of the chorioallantoic
      placenta. Usually the chorioallantoic placenta progressively displaces the area
      of contact of the yolk sac placenta with the endometrium. It is also closely
      applied to the endometrium, increasing respiratory efficiency but tending to
      decrease histotrophic nutrition. Catarrhine primates have minimal histotrophic
      uptake, using haemotrophic mechanisms throughout most of gestation. Rodents, by
      using partial or complete inversion of the yolk sac, have extensive regions
      available to histotroph in later pregnancy. Most mammals, however, have developed
      specialized regions of the chorioallantoic placenta for ingestion of uterine
      secretions, cell debris and erythrocytes. These regions vary from simple saccular
      areolae to more complex areolae such as the chorionic vesicles of prosimian
      primates to specialized haemophagous areas. All such structures are consistently
      lined by columnar cellular trophoblast. Examples of these structures, many of
      which can ingest both glandular secretions and erythrocytes (i.e. they are
      heterophagous), can be found in species whose definitive placenta is
      epitheliochorial. They are common but not universal in species whose definitive
      placenta is endotheliochorial and are even found in a few species with definitive
      haemochorial placentas. Restriction of phagocytosis to regions of columnar cells
      provides polarized cells appropriately oriented for ingestion, breakdown and
      transport, and limits the type of ingestion of both beneficial and potentially
      toxic materials to expendable individual cells.

PMID- 16406005
TI  - Use of biliary PAH metabolites as a biomarker of pollution in fish from the
      Baltic Sea.
AB  - During field campaigns of the BEEP project (Biological Effects of Environmental
      Pollution in Marine Coastal Ecosystems) in 2001-2002, metabolites of polycyclic
      aromatic hydrocarbons (PAHs) were determined in bile samples from three fish
      species, flounder (Platichthys flesus), perch (Perca fluviatilis) and eelpout
      (Zoarces viviparus), from four separate areas in the Baltic Sea. Two
      determination methods were applied: fixed wavelength fluorescence (FF) for pyrene
      type metabolites and high-performance liquid chromatography with fluorescence
      detection (HPLC). There was a good correlation between the FF method and 1-OH
      pyrene determined by HPLC. Normalisation of the FF data for absorbance at 380 nm
      or bile protein concentrations greatly increased variance in one third and
      decreased it in two thirds of the cases and resulted in a loss of significant
      differences (protein normalisation) between the sampling stations, but
      normalisation of the HPLC data had little effect on the results. The biliary PAH
      metabolite content was usually higher in males than in females. In perch and
      eelpout the biliary PAH contents were at similar levels, whereas in flounder the
      levels were lower. The sampling areas arranged in decreasing order of biliary PAH
      contents were: Wismar Bay > Gulf of Gdansk > Lithuanian coast > Kvadofjarden
      (reference area). It is concluded that FF with un-normalised data is a reliable
      and simple method for monitoring purposes and only one sex of a selected species
      should be used.

PMID- 16406006
TI  - The significance of dilution in evaluating possible impacts of wastewater
      discharges from large cruise ships.
AB  - In response to public concerns about discharges from large cruise ships, Alaska's
      Department of Environmental Conservation (ADEC) sampled numerous effluents in the
      summer of 2000. The data showed that basic marine sanitation device (MSD)
      technology for black water (sewage) was not performing as expected. Untreated
      gray water had high levels of conventional pollutants and surprisingly high
      levels of bacteria. Both black water and gray water discharges sometimes exceeded
      state water quality standards for toxicants. The state convened a Science
      Advisory Panel (the Panel) to evaluate impacts associated with cruise ship
      wastewater discharges. The effluent data received wide media coverage and
      increased public concerns. Consequently, legislative decisions were made at the
      State and Federal level, and regulations were imposed before the Panel completed
      its evaluation. The Panel demonstrated that following the rapid dilution from
      moving cruise ships, the effluent data from the Summer of 2000 would not have
      exceeded water quality standards, and environmental effects were not expected.

PMID- 16406007
TI  - Toward constructing an endophenotype strategy for bipolar disorders.
AB  - Research aimed at elucidating the underlying neurobiology and genetics of bipolar
      disorder, and factors associated with treatment response, have been limited by a
      heterogeneous clinical phenotype and lack of knowledge about its underlying
      diathesis. We used a survey of clinical, epidemiological, neurobiological, and
      genetic studies to select and evaluate candidate endophenotypes for bipolar
      disorder. Numerous findings regarding brain function, brain structure, and
      response to pharmacological challenge in bipolar patients and their relatives
      deserve further investigation. Candidate brain function endophenotypes include
      attention deficits, deficits in verbal learning and memory, cognitive deficits
      after tryptophan depletion, circadian rhythm instability, and dysmodulation of
      motivation and reward. We selected reduced anterior cingulate volume and early
      onset white matter abnormalities as candidate brain structure endophenotypes.
      Symptom provocation endophenotypes might be based on bipolar patients'
      sensitivity to sleep deprivation, psychostimulants, and cholinergic drugs.
      Phenotypic heterogeneity is a major impediment to the elucidation of the
      neurobiology and genetics of bipolar disorder. We present a strategy constructed
      to improve the phenotypic definition of bipolar disorder by elucidating candidate
      endophenotypes. Studies to evaluate candidate endophenotypes with respect to
      specificity, heritability, temporal stability, and prevalence in unaffected
      relatives are encouraged.

PMID- 16406008
TI  - Phosphorylation sites on calcium channel alpha1 and beta subunits regulate ERK
      dependent modulation of neuronal N-type calcium channels.
AB  - Voltage-dependent calcium channels (VDCCs) in sensory neurones are tonically up
      regulated via Ras/extracellular signal regulated kinase (ERK) signalling. The
      presence of putative ERK consensus sites within the intracellular loop linking
      domains I and II of neuronal N-type (Ca(v)2.2) calcium channels and all four
      neuronal calcium channel beta subunits (Ca(v)beta), suggests that Ca(v)2.2 and/or
      Ca(v)betas may be ERK-phosphorylated. Here we report that GST-Ca(v)2.2 I-II loop,
      and to a lesser extent Ca(v)beta1b-His(6), are substrates for ERK1/2
      phosphorylation. Serine to alanine mutation of Ser-409 and/or Ser-447 on GST
      Ca(v)2.2 I-II loop significantly reduced phosphorylation. Loss of Ser-447 reduced
      phosphorylation to a greater extent than mutation of Ser-409. Patch-clamp
      recordings from wild-type Ca(v)2.2,beta1b,alpha2delta1 versus mutant
      Ca(v)2.2(S447A) or Ca(v)2.2(S409A) channels revealed that mutation of either site
      significantly reduced current inhibition by UO126, a MEK (ERK kinase)-specific
      inhibitor that down-regulates ERK activity. However, no additive effect was
      observed by mutating both residues together, suggesting some functional
      redundancy between these sites. Mutation of both Ser-161 and Ser-348 on
      Ca(v)beta1b did not significantly reduce phosphorylation but did reduce UO126
      induced current inhibition. Crucially, co-expression of Ca(v)2.2(S447A) with
      Ca(v)beta1b(S161,348A) had an additive effect, abolishing the action of UO126 on
      channel current, an effect not seen when Ca(v)beta1b(S161,348A) was co-expressed
      with Ca(v)2.2(S409A). Thus, Ser-447 on Ca(v)2.2 and Ser-161 and Ser-348 of
      Ca(v)beta1b appear to be both necessary and sufficient for ERK-dependent
      modulation of these channels. Together, our data strongly suggest that modulation
      of neuronal N-type VDCCs by ERK involves phosphorylation of Ca(v)2.2alpha1 and to
      a lesser extent possibly also Ca(v)beta subunits.

PMID- 16406009
TI  - Continuous and tractable models for the variation of evolutionary rates.
AB  - We propose a continuous model for variation in the evolutionary rate across sites
      and over the phylogenetic tree. We derive exact transition probabilities of
      substitutions under this model. Changes in rate are modelled using the CIR
      process, a diffusion widely used in financial applications. The model directly
      extends the standard gamma distributed rates across site model, with one
      additional parameter governing changes in rate down the tree. The parameters of
      the model can be estimated directly from two well-known statistics: the index of
      dispersion and the gamma shape parameter of the rates across sites model. The CIR
      model can be readily incorporated into probabilistic models for sequence
      evolution. We provide here an exact formula for the likelihood of a three-taxon
      tree. The likelihoods of larger trees can be evaluated using Monte-Carlo methods.

PMID- 16406010
TI  - The three-dimensional detection of microvasculatory bed in the brain of white rat
      Rattus norvegicus by a Ca2+-ATPase method.
AB  - A procedure is described which allows for the selective and non-injectional
      staining of the three-dimensional microvasculatory bed (MVB) in thick sections
      (60-140 microm) of formalin-fixed brain tissue of white rats Rattus norvegicus.
      This histochemical method detects ATPase activity and takes place between pH 10.5
      and 11.2. Calcium ion is used to capture inorganic phosphate, calcium phosphate
      is converted to lead phosphate, and subsequently converted to black or dark brown
      lead sulfide. All vessels are revealed due to a precipitate on the endothelium
      and smooth muscle cells of arterioles. In some vessels, red blood cells also
      stain. The background is transparent with no staining of neurons, nerve fibers,
      glial cells, or nuclei. This allows for clear identification of arterioles,
      venules, and capillaries, which is difficult using other methods. New
      observations are described including the presence of webs connecting branching
      parts of arterioles and constrictions along vessels. This procedure should be
      useful in investigations of the MVB in rat brain.

PMID- 16406011
TI  - Dose-dependent reductions in spatial learning and synaptic function in the
      dentate gyrus of adult rats following developmental thyroid hormone
      insufficiency.
AB  - Thyroid hormones are critical for the development and maturation of the central
      nervous system. Although somatic and neurological effects are well documented
      following severe thyroid hormone deprivation, much less is known of the
      functional consequences of moderate levels of hormone insufficiency. We have
      previously demonstrated that severe thyroid hormone reductions in the postnatal
      period are associated with impairments in synaptic transmission in the dentate
      gyrus. The present study was performed to examine the dose-response relationships
      of moderate levels of hormone disruption on synaptic function in the dentate
      gyrus in an in vivo preparation and to determine the effects on spatial learning.
      Pre- and postnatal thyroid hormone insufficiency was induced by administration of
      3 or 10 ppm propylthiouracil (PTU) to pregnant and lactating dams via the
      drinking water from gestation day (GD) 6 until postnatal day (PN) 30. This
      regimen produced a 47% and 65% reduction in serum T4, in the dams of the low and
      high-dose groups, respectively. At the time of testing of adult offspring,
      hormone status had returned to control levels. In littermates, field potentials
      evoked in the dentate gyrus in response to stimulation of the perforant path were
      assessed under urethane anesthesia. The data reveal dose-dependent reductions in
      synaptic transmission and impairments in long-term potentiation (LTP) of the EPSP
      component of the compound field potential. In contrast, LTP of the population
      spike measure was paradoxically enhanced. Spatial learning in the Morris water
      maze was profoundly impaired in high-dose animals. Although the majority of
      subjects in the low-dose group eventually acquired the task, their acquisition
      rate lagged behind control values. Reversal learning was assessed in all animals
      reaching criterion performance and found to be impaired in PTU-exposed animals
      relative to controls. These data support previous findings in area CA1 in vitro,
      extend observations associated with dentate gyrus synaptic function to a lower
      dose range, and provide correlative evidence of behavioral disruption in a
      hippocampal-dependent learning task following developmental thyroid hormone
      insufficiency.

PMID- 16406012
TI  - Effects of spatial separation and stimulus probability on the event-related
      potentials elicited by occasional changes in sound location.
AB  - The ability to extract information about the spatial location of sounds plays an
      important role in auditory scene analysis. The present study examined the effects
      of spatial separation and stimulus probability on auditory event-related
      potentials (ERPs) to changes in sound location. In Experiment 1, we found that
      difference waves between ERPs elicited by standard and deviant stimuli showed a
      biphasic negative-positive response peaking around 126 and 226 ms after deviant
      onset. The amplitude of both responses increased with decreasing deviant stimulus
      probability, and increasing stimulus deviance. When the same stimuli were
      presented with equal probability for all locations (Experiment 2), there were no
      significant differences in the ERP amplitude and latency. These results suggest
      that the data reported in Experiment 1 are the result of contextual changes,
      rather than changes in simple acoustic features. Brain electrical source analyses
      are consistent with generators located in auditory cortices posterior to
      Heschel's gyrus. Although occasional changes in sound location elicit earlier
      peaks than the mismatch negativity (MMN) response reported for other types of
      deviation, their topographical distribution and behavior are consistent with MMN.
      The early latency of MMN for changes in sound location is interpreted in the
      context of an early-warning system to alert the organism to new sound sources in
      the environment.

PMID- 16406013
TI  - Electrophysiological characterization of nicotinic acetylcholine receptors in cat
      petrosal ganglion neurons in culture: effects of cytisine and its bromo
      derivatives.
AB  - Petrosal ganglion neurons are depolarized and fire action potentials in response
      to acetylcholine and nicotine. However, little is known about the subtype(s) of
      nicotinic acetylcholine receptors involved, although alpha4 and alpha7 subunits
      have been identified in petrosal ganglion neurons. Cytisine, an alkaloid
      unrelated to nicotine, and its bromo derivatives are agonists exhibiting
      different affinities, potencies and efficacies at nicotinic acetylcholine
      receptors containing alpha4 or alpha7 subunits. To characterize the receptors
      involved, we studied the effects of these agonists and the nicotinic
      acetylcholine receptor antagonists hexamethonium and alpha-bungarotoxin in
      isolated petrosal ganglion neurons. Petrosal ganglia were excised from
      anesthetized cats and cultured for up to 16 days. Using patch-clamp technique, we
      recorded whole-cell currents evoked by 5-10 s applications of acetylcholine,
      cytisine or its bromo derivatives. Agonists and antagonists were applied by
      gravity from a pipette near the neuron surface. Neurons responded to
      acetylcholine, cytisine, 3-bromocytisine and 5-bromocytisine with fast inward
      currents that desensitized during application of the stimuli and were reversibly
      blocked by 1 microM hexamethonium or 10 nM alpha-bungarotoxin. The order of
      potency of the agonists was 3-bromocytisine >> acetylcholine approximately =
      cytisine >> 5-bromocytisine, suggesting that homomeric alpha7 neuronal nicotinic
      receptors predominate in cat petrosal ganglion neurons in culture.

PMID- 16406014
TI  - Prior information of stimulus location: effects on ERP measures of visual
      selection and response selection.
AB  - This paper examines the effects of prior information of the location of an
      upcoming stimulus on event-related EEG potentials associated with the focusing of
      attention. Results of two tasks, reported in a previous publication (Praamstra,
      P., Boutsen, L., Humphreys, G.W., 2005. Frontoparietal control of spatial
      attention and motor intention in human EEG. J. Neurophysiol. 94, 764-774), were
      compared: one in which spatial attention was cued to the stimulus location and
      one in which the cue was non-informative. Only informative directional cues
      elicited directing-attention EEG potentials in the delay period between cue and
      target. Notwithstanding these electrophysiological signs of an attentional
      orientation prior to the occurrence of the target, there were no reaction time
      effects related to the presence of advance spatial information. By contrast, the
      advance information did have effects on EEG potentials following the target
      stimulus. The N2pc, reflecting an attentional selection mechanism in extrastriate
      cortex, was reduced in amplitude with advance spatial information. The N2cc,
      coinciding in time with the N2pc but measured over the motor cortex, was
      preempted by the advance spatial information. These results support that the N2cc
      is not due to overlap of the N2pc with movement execution-related activity. It is
      proposed that the neural activity underlying this EEG potential arises from the
      dorsal premotor cortex and serves an executive-attentional function that helps to
      ensure that the selection of a manual response is not biased by the direction of
      spatial attention.

PMID- 16406015
TI  - Use of simplified strategies to evaluate early treatment response in childhood
      acute lymphoblastic leukemia.
AB  - Early treatment response assessment has become an import prerequisite in the
      selection therapy in childhood ALL. In this study we compare classical diagnostic
      factors and the significance of three simplified strategies, WBC count at day 7
      and a simplified PCR methodology to minimal residual disease detection on days 14
      and 28, to evaluate early treatment response in 84 consecutive children with ALL.
      The use of these simplified methods for the evaluation of early response, proved
      to be a good predictor of an unfavorable course in children with ALL and could be
      used as a stratification criterion in treatment protocols, specially in low
      budget countries.

PMID- 16406016
TI  - FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice,
      long-term experience with imatinib therapy, and a critical review of the
      literature.
AB  - We previously studied clinico-pathologic features of 89 consecutive adult
      patients with moderate-to-severe eosinophilia, and reported a FIP1L1-PDGFRA
      prevalence of 12%. In that series, all 11 FIP1L1-PDGFRA+ patients receiving
      imatinib achieved a complete response. We now extend our observations through a
      study of 741 unselected patients with eosinophilia for FIP1L1-PDGFRA, and present
      longer term follow up data for the imatinib-treated cohort. We also include data
      for three previously unreported FIP1L1-PDGFRA+ patients. Among the 741 requests,
      only 21 (3%) were found to carry the FIP1L1-PDGFRA mutation. While all 14 FIP1L1
      PDGFRA+ patients receiving imatinib achieved a complete response, the 4 patients
      who attempted to discontinue imatinib all relapsed. We also find that it is
      possible to maintain patients in clinical remission with an empirically derived
      schedule of low-dose (50-100 mg), intermittent (once daily to once weekly)
      imatinib. Lastly, we present a comprehensive review of the literature pertaining
      to FIP1L1-PDGFRA in order to address several key aspects of this mutation from a
      clinical standpoint.

PMID- 16406017
TI  - Is chronic lymphocytic leukemia a response to infectious agents?

PMID- 16406018
TI  - Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM
      CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and
      response to therapy with imatinib.
AB  - Based on generally accepted criteria and the WHO-classification, a subset of
      patients with systemic mastocytosis (SM) have (or develop) an associated clonal
      hematologic non-mast cell lineage disease (SM-AHNMD). We describe a case of SM
      with coexisting chronic eosinophilic leukemia (SM-CEL). The patient, a 51-year
      old male, was first seen in 1992 with small-sized infiltrates of spindle-shaped
      mast cells in his marrow, and marked eosinophilia. Retrospectively, a CHIC2
      deletion and the FIP1L1/PDGFRalpha fusion gene-product were demonstrable by FISH
      analysis and RT-PCR, respectively. SM-associated organopathy or mediator-related
      symptoms were not recorded. However, the patient developed cardiomyopathy.
      Therapy with interferon-alpha, hydroxyurea, and corticosteroids were without
      effects. By contrast, therapy with imatinib was followed by a fast and sustained
      response with complete and stable regression of eosinophilia, drop in eosinophil
      cationic protein, and decrease of serum tryptase to normal levels. This case
      provides further evidence for the potential of co-existence of SM with a primary
      eosinophilic disorder (CEL) defined by the FIP1L1/PDGFRalpha fusion gene. Because
      of the availability of a superior targeted drug (imatinib), it is of importance
      to screen for FIP1L1/PDGFRalpha in suspected CEL with or without co-existing SM.

PMID- 16406020
TI  - Expression of the testis-specific gene, TSGA10, in Iranian patients with acute
      lymphoblastic leukemia (ALL).
AB  - Testis-specific gene antigen (TSGA10) is expressed in fetus, testis and
      frequently in human solid cancers and acute leukemias, making it a candidate for
      immunotherapy and for detection of minimal residual disease (MRD). This gene is
      considered as a member of cancer-testis (CT) genes. We previously demonstrated
      TSGA10 expression during spermatogenesis. There is also evidence for potential
      TSGA10 involvement in cell proliferation. TSGA10 expression has been observed in
      a wide spectrum of cancers but not in hematopoietic neoplasm. Here we
      demonstrated expression of TSGA10 by semi-quantitative RT-PCR in 44 (84.6%) out
      of 52 bone marrow samples and all peripheral blood samples from patients with
      acute lymphoblastic leukemia (ALL). Twenty-seven (52%) cases had high level of
      gene expression and 16 (30.7%) cases had a lower expression level of the gene in
      the patients bone marrow. Presence of TSGA10 expression in ALL may open a window
      to functional study of mitotic checkpoint proteins in leukemia. RT-PCR of TSGA10
      may help in detection of residual clonal cells leading to early diagnosis and
      better prognostic qualification of the disease.

PMID- 16406019
TI  - Do childhood diseases affect NHL and HL risk? A case-control study from northern
      and southern Italy.
AB  - To investigate the association between non-Hodgkin lymphoma (NHL), Hodgkin
      lymphoma (HL), and exposure to childhood diseases, we analyzed an Italian case
      control study that included 225 histologically-confirmed incident cases of NHL,
      62 HL cases, and 504 controls. After adjusting for confounding factors, all
      examined childhood diseases were negatively associated with HL. Measles was
      negatively associated with NHL, particularly follicular B-cell NHL. Our findings
      provide additional support to the hypothesis that infections by most common
      childhood pathogens may protect against HL or, at least, be correlated with some
      other early exposure, which may lower the risk of HL in adulthood. In addition,
      our study shows that measles may provide a protective effect against NHL.

PMID- 16406021
TI  - Novel neuroprotective effects of the aqueous extracts from Verbena officinalis
      Linn.
AB  - Verbena officinialis Linn. (Verbenaceae) is a perennial plant which has been used
      as herbal medicine or health supplement in both Western and Eastern countries for
      centuries. It has been used to treat acute dysentery, enteritis, amenorrhea and
      depression. In view of its wide array of biological effects, we hypothesized that
      V. officinalis can exert cytoprotective effects on cells of the central nervous
      system. Pre-treatment of aqueous extracts of V. officinalis significantly
      attenuated the toxicity of beta-amyloid (Abeta) peptide and reducing agent
      dithiothreitol in primary cultures of cortical neurons. As extracellular
      accumulation of Abeta peptide is an important cytotoxic factor involved in
      Alzheimer's disease (AD), we have further explored its neuroprotective effect
      against Abeta. Treatment of V. officinalis attenuated Abeta-triggered DEVD- and
      VDVAD-cleavage activities in a dose-dependent manner. Further studies elucidated
      that phosphorylation of both interferon-inducing protein kinase (PKR) and c-Jun N
      terminal kinase (JNK) was attenuated in Abeta-treated neurons. Taken together, we
      have proved our hypothesis by showing the novel neuroprotective effects of V.
      officinalis. As V. officinalis has long been used for many years to be a folk
      medicine, our study may provide a lead for its potential to be a neuroprotective
      agent against neuronal loss in AD.

PMID- 16406023
TI  - Age-related incidence curve of hospitalized Shaken Baby Syndrome cases:
      convergent evidence for crying as a trigger to shaking.
AB  - OBJECTIVE: To determine whether there is an age-specific incidence of
      hospitalized cases of Shaken Baby Syndrome (SBS) that has similar properties to
      the previously reported "normal crying curve," as a form of indirect evidence
      that crying is an important stimulus for SBS. DESIGN AND SETTING: The study
      analyzed cases of Shaken Baby Syndrome by age at hospitalization from hospital
      discharge data for California hospitals from October 1996 through December 2000.
      PATIENTS: All cases of children less than 18 months (78 weeks) of age for whom
      the diagnostic code for Shaken Baby Syndrome (995.55) in the International
      Classification of Disease, Ninth Edition, Clinical Modification was assigned.
      RESULTS: There were 273 hospitalizations for SBS. Like the "normal crying curve,"
      the curve of age-specific incidence starts at 2-3 weeks, has a clear peak, and
      declines to baseline by about 36 weeks of age. In contrast to the normal crying
      curve that peaks at 5-6 weeks, the peak of SBS hospitalizations occurs at 10-13
      weeks. CONCLUSIONS: The age-specific incidence curve of hospitalized SBS cases
      has a similar starting point and shape to the previously reported normal crying
      curve but the peak occurs about 4-6 weeks later. Of the likely predisposing
      causes, this pattern is only consistent with the properties of early crying.
      There are numerous explanations for the lag in the peaks between crying and SBS
      hospitalizations, including the possibility of repeat shakings prior to
      hospitalization. The importance of crying as a stimulus to SBS may provide an
      opportunity for preventive intervention.

PMID- 16406024
TI  - Mothers in substance abuse treatment: differences in characteristics based on
      involvement with child welfare services.
AB  - PROBLEM: Greater awareness of the role of parental substance abuse in child
      maltreatment makes it imperative that the substance abuse treatment and child
      welfare systems coordinate services for these parents. Yet little is known about
      the characteristics of child-welfare involved parents (primarily mothers) who
      enter into substance abuse treatment. This paper compares the characteristics of
      mothers in substance abuse treatment who were and were not involved with child
      welfare services, and discusses the treatment implications of these differences.
      METHOD: Data were obtained from a statewide treatment outcome monitoring project
      in California. Clients were assessed at treatment admission using the Addiction
      Severity Index. Bivariate analyses and multivariate logistic regression were
      conducted comparing mothers who were (N=1,939) and were not (N=2,217) involved
      with child welfare. RESULTS: Mothers who were involved with child welfare were
      younger, had more children, and had more economic problems. They were more likely
      to be referred by the criminal justice system or other service providers, to have
      a history of physical abuse, and to be treated in outpatient programs. They had
      lower levels of alcohol severity, but did not differ with regard to psychiatric
      severity or criminal involvement. Primary users of methamphetamine were
      disproportionately represented among this group and had a distinct profile from
      primary alcohol- and opiate-users. CONCLUSION: Study findings suggest that
      mothers involved with child welfare enter substance abuse treatment through
      different avenues and present a clinical profile of treatment needs related to
      exposure to physical abuse, economic instability, and criminal justice
      involvement.

PMID- 16406025
TI  - Associations between maternal childhood maltreatment and psychopathology and
      aggression during pregnancy and postpartum.
AB  - OBJECTIVE: This study examines the association between maternal childhood
      maltreatment and psychopathology and aggression in intimate relationships during
      pregnancy and the postpartum period. METHOD: Forty-four pregnant women who were
      recruited from an obstetric clinic and local advertising periodical completed
      questionnaires about childhood maltreatment and psychopathology during their
      first trimester of pregnancy. Approximately 1 year after the birth of the child,
      32 of the original participants completed these same questionnaires. Regression
      models were used to test the relationship between childhood maltreatment and
      psychopathology and aggression during pregnancy and 1 year postpartum. RESULTS:
      Sexual abuse and emotional neglect were related to psychopathology during
      pregnancy, and emotional neglect and physical abuse and neglect predicted poorer
      maternal outcomes 1 year postpartum. Contrary to expectations, physical abuse was
      related to less aggression during pregnancy, and emotional abuse was associated
      with less pathology postpartum. CONCLUSIONS: The results of this study indicate
      that childhood maltreatment is associated with poorer maternal mental health
      during pregnancy and 1 year postpartum and points to the need to improve
      targeting and treatment of psychopathology during this time.

PMID- 16406026
TI  - Measuring the potential for child maltreatment: the reliability and validity of
      the Adult Adolescent Parenting Inventory--2.
AB  - OBJECTIVE: The field of child protection needs reliable and valid methods of
      assessing the potential for child abuse and neglect. The purpose of this study
      was to examine the psychometric properties of the Adult Adolescent Parenting
      Inventory--2 (AAPI-2), Form B, using a sample of 309 low-income, rural families
      in a southern state. METHOD: The AAPI-2 is a 40-item survey designed to assess
      the parenting and child rearing attitudes of adult and adolescent parent and pre
      parent populations. Each of the five AAPI-2 scales was (a) examined using factor
      analysis in order to determine the unidimensionality of the scale, (b) evaluated
      based on estimates of the scales reliability in order to determine the
      consistency with which the construct was measured, and (c) when possible,
      examined to determine if it is related to other constructs in meaningful and
      expected ways. RESULTS: While the factor structure reported by the developer was
      not fully confirmed in this sample, there is some evidence that the instrument is
      measuring at least two of the constructs it purports to measure and that the
      total score may be useful. Correlations with other instruments measuring
      parenting behavior and child behavior were significant, and in the expected
      direction, offering some support for the validity of the AAPI-2. CONCLUSIONS:
      While the AAPI-2 appears to measure attitudes related to harsh or neglectful
      parenting, caution should be used in the interpretation of the individual AAPI-2
      scales.

PMID- 16406027
TI  - Structure of dihydroxyacetone phosphate dimethyl acetal, a stable
      dihydroxyacetone phosphate precursor, in the crystalline state.
AB  - Crystal and molecular structures of four different salts of a dihydroxyacetone
      phosphate (DHAP) precursor, its dimethyl acetal [2,2-dimethoxy-1,3-propanediol
      phosphate, C(5)H(13)O(7)P, (MeO)(2)DHAP]: (cha)(2)[(MeO)(2)DHAP].H(2)O (6a),
      (cha)[(MeO)(2)DHAP] (6b), Na(2)[(MeO)(2)DHAP].5.75H(2)O (6c) and
      K(2)[(MeO)(2)DHAP].H(2)O (6d), along with the cyclohexylammonium (cha) salt of
      its phenyl ester (cha)[(MeO)(2)DHAP(Ph)] (6e) are described. In the (MeO)(2)DHAP
      mono- and dianions, slightly different orientation of the phosphate group in
      relation to the acetal carbon atom is observed, with a delicate tendency of
      phosphate group to be located antiperiplanar in the monoanions and anticlinal in
      the dianions. The 2,2-dimethoxy-1,3-propandiol moiety, (MeO)(2)DHA, seems to be
      very rigid and its conformation is independent of phosphorylation, the ionization
      state of the inserted phosphate group and its additional substitution. The
      overall structures of the cyclohexylammonium (6a,b) and potassium salts (6d) have
      a double-layered architecture, while the sodium cation network in 6c forms the
      system of channels, which are filled up with the [(MeO)(2)DHAP](2-) ions. The
      different architectures of 6c and 6d crystals result from the different ways in
      which the relevant dianions coordinate to sodium and potassium ions and affect
      also the hydrogen bonding system observed in 6c and 6d crystals.

PMID- 16406028
TI  - Interaction between space and number representations during motor preparation in
      manual aiming.
AB  - The existence of a spatial component in the representation of number magnitude
      has been repeatedly supported by the demonstration that the left hand responds
      faster to smaller numbers, whereas the right hand responds faster to larger
      numbers. These results support the view that the 'mental number line' is oriented
      such that smaller numbers are associated with the left side of space while larger
      numbers are associated with the right side. We investigated whether the link
      between spatial and number processing arises from a continuous or categorical
      mapping between space and number representations. The investigation was designed
      to study all aspects of the motor act, including both planning and execution
      phases. For this purpose we measured reaction times (RTs), movement times (MTs),
      spatial accuracy, and endpoint pressure of manual aiming, while subjects reached
      with the right hand towards the location of a visual digit target. Five different
      digits were equiprobably presented at five positions along the horizontal axis. A
      GO/NO-GO choice task paradigm was used to ensure that digit parity (i.e.,
      odd/even) was being processed. Analyses of MT, accuracy, and pressure data showed
      no digit effects. However, two number-related effects were observed on RTs.
      First, shorter RTs were obtained for smaller digits independent of target
      location, despite the use of the right hand. Second, an interaction was observed
      between target location and number magnitude whereby relative RTs were shortest
      when there was a congruity between target magnitude and location. These results
      imply that motor preparation is contaminated both by the direct activation of
      number magnitude and by the congruity between the spatial location of a target
      number and its magnitude. We conclude that continuous mapping intervenes between
      mental number representation and physical space.

PMID- 16406029
TI  - The role of cardiac myosin binding protein-C as a regulator of myofilament Ca2+
      sensitivity.

PMID- 16406030
TI  - Seizure duration following sarin exposure affects neuro-inflammatory markers in
      the rat brain.
AB  - The current study was aimed to characterize for the first time the alterations in
      the characteristic neuro-inflammatory markers triggered by sarin exposure in the
      rat's brain, and to investigate its dependency on seizure duration. Centrally
      mediated seizures are a common consequence of exposure to organophosphates (OP)
      despite conventional treatment with atropine and an oxime. In the present study
      midazolam, was used to control duration and intensity of seizures. The levels of
      the pro-inflammatory cytokine peptides IL-1beta, IL-6, TNF-alpha and
      prostaglandin E2 (PGE2) were monitored at various times after sarin exposure in
      the hippocampus and cortex of rats treated with midazolam following 5 or 30 min
      of seizure activity. Biochemical evaluation of brain tissues revealed a
      significant increase in the level of the pro-inflammatory peptides starting at 2
      h and peaking at 2-24 h following sarin. Hippocampal values of IL1-beta increased
      from 1.2+/-0.1 pg/mg tissue (control), to 2.4+/-0.3 at 2 h (5 min seizure) and to
      9.3+/-2.5 at 8h (30 min seizure). PGE2 level in the hippocampus increased up to
      24 h following exposure (from 56+/-3 to 175+/-26 and 277+/-28 pg/mg tissue)
      following 5 and 30 min of seizure activity respectively. Thus, unlike limitation
      of seizures to 5 min by midazolam, delayed treatment (30 min) resulted in
      prolonged seizures and pronounced increase in cytokines and PGE2. In addition, a
      second increase in inflammatory markers was observed 30 days following sarin
      exposure only in rats treated following 30 min of seizure activity. Histological
      evaluation of the rat brain, conducted in this study, revealed lack of damage in
      the hippocampus and piriform cortex with minor lateral ventricles enlargement in
      few animals following 5 min of sarin-induced seizure activity. In contrast,
      marked histological damage to the brain was demonstrated following 30 min of
      seizure activity, consisting severe damage to the hippocampus, piriform cortex
      and some thalamic nuclei. In summary, a novel characterization of the prolonged
      central neuro-inflammatory process that accompanies sarin exposure is presented.
      The timing of the anticonvulsive treatment was shown to be crucial in modulation
      of the neuro-inflammatory response, and may implicate the consequent long-term
      brain damage.

PMID- 16406031
TI  - Sertraline delays the somatic growth and reflex ontogeny in neonate rats.
AB  - This study investigated the somatic maturation and ontogeny of reflexes in
      neonate rats treated with sertraline (Sert) during the suckling period. The
      animals were divided into four groups; three that received daily doses of Sert
      (5, 10 or 15 mg/kg s.c.; groups Sert5, Sert10, and Sert15, respectively), and a
      fourth group that received distilled water (Dw) (1 ml/kg/b.w.). Growth indicators
      (body weight, axis of the head and tail length) were measured daily, from the 1st
      to the 21st postnatal day. The reflexes (righting, free-fall righting, negative
      geotaxis, cliff avoidance, auditory startle response, vibrissa placing and palm
      grasp) and physical-feature maturation (ear unfolding, auditory conduit opening,
      irruption of the lower incisors and eye opening) were recorded each day of the
      animal's life. All groups were compared to the Dw group. The body weight gain was
      reduced in all the Sert groups. Moreover, a delay in the growth of the body
      length was observed in all the Sert groups. Higher Sert doses reduced the speed
      of growth in the tail length. The medio-lateral head axis reduced in Sert15 and
      Sert5 doses. Otherwise, Sert10 had a temporary acceleration in this growth, but
      the growth of the anteroposterior head axis had a delay in all the Sert groups.
      The highest doses induced a delay in physical-feature maturation. The palm grasp
      reflex (disappearance) was retarded in Sert10; cliff avoidance advanced in
      Sert10; negative-geotaxis and free-fall righting retarded in Sert15. The findings
      suggest that altered serotonergic system activity induced by sertraline early in
      life could play a role in the retardation of the somatic growth ontogeny as well
      as a delay in the maturation of some reflexes.

PMID- 16406032
TI  - Optimization of dansyl derivatization and chromatographic conditions in the
      determination of neuroactive amino acids of biological samples.
AB  - BACKGROUND: Amino acid neurotransmitters represent a major class of compounds
      that are involved in neuronal communication at CNS synapses. METHODS: Twelve
      amino acids were separated after precolumn derivatization with dansyl chloride.
      The biologically important amino acids, taurine, aspartate, glutamate, glycine,
      alanine and gamma-aminobutyric acid were determined in rat brain tissue and
      rabbit plasma. RESULTS: The major modifications to previous methods included
      isocratic elution instead of gradient elution to reduce time and cost of serial
      analyses; optimization of mobile phase to improve the separation of free dansyl
      with derivatives, so as to elide complex steps for the clean of the chromatogram;
      and selection of an internal standard (Trazodone) to improve the reproducibility
      and the reliability of procedures. Twelve amino acids were assayed within 35 min.
      Other alpha-amino acids that are relevant to the make-up of mammalian proteins
      did not interfere with the determination. The standard curve, recovery,
      analytical precision and detection limits for each neuroactive amino acid were
      determined. CONCLUSION: This assay separated 12 amino acids in a single run. Six
      neuroactive amino acids were also simultaneous measured by isocratic HPLC with UV
      detection. The method is applicable in determination of Tau, Glu, Asp, Gly, Ala
      and GABA in biological samples.

PMID- 16406033
TI  - Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous
      liaison in Alzheimer's disease and other disorders.
AB  - Almost a hundred years ago, the main neuropathological features of Alzheimer's
      disease (AD) brain were discovered, yet the underlying cause(s) are still
      unknown, and the disease is basically untreatable. Despite the very numerous
      studies on the neuropathological features, the cause(s) of their production and
      whether they have an aetiological role in the disease or are merely end-products
      ("tombstones") are still unknown. Indeed, until fairly recently, the only known
      risk factors were age, Down's syndrome and head injury. A susceptibility factor,
      the type 4 allele of the apolipoprotein E gene was identified, but it is neither
      essential nor sufficient to cause AD, so other factors must be involved also. We
      investigated the possibility of a viral role and discovered that HSV1 DNA is
      present in brain of a high proportion of elderly people and that in combination
      with APOE-epsilon4 it confers a high risk of AD. Subsequently, we found that APOE
      determines outcome of infection in several diseases caused by diverse infectious
      agents. Here we describe our studies, and the few others carried out elsewhere,
      on the mechanism of action of HSV1 and the dependence of the damage on APOE. We
      discuss, in relation to HSV1 action on lipids and to the spread of the virus via
      lipid rafts in brain, the possible involvement in AD of cholesterol, a vital and
      major component of the human brain, and the dispute over whether statins, drugs
      used for lowering cholesterol levels, are protective against the disease. We also
      link the damage due to two major consequences of HSV1 infection--inflammatory and
      oxidative processes--to lipid peroxidation in brain, and consider the influence
      of the different apoE isoforms in this process.

PMID- 16406034
TI  - Genital schistosomiasis in women: a clinical 12-month in vivo study following
      treatment with praziquantel.
AB  - Urinary schistosomiasis is known to be associated with lesions in the female
      genital organs, particularly with the presence of 'sandy patches' in the lower
      genital tract. This study sought to determine the effect of treatment with
      praziquantel on gynaecological schistosomiasis in residents of an area endemic
      for Schistosoma haematobium. A cohort study was conducted among women aged 20-49
      years in rural Zimbabwe. The shape and size of lesions were mapped pre treatment
      and 3 and 12 months following treatment. Ova of S. haematobium were looked for in
      cytology smears, wet mounts, biopsies, urine and stool. Specimens were collected
      for detection of sexually transmitted diseases and cancer. At baseline, almost
      half of the 527 women included in the study had sandy patches. Although urinary
      ova excretion decreased following treatment (odds ratio 10.3, 95% CI 3.8-27.8,
      P<0.001), praziquantel treatment was not associated with a significant reduction
      in genital lesions or contact bleeding (P=0.31-0.94). Sandy patches remained
      strongly associated with contact bleeding and vessel abnormalities even after
      treatment. Findings were independent of HIV status. Such lesions, which are
      common and apparently refractory to treatment for at least 12 months, may be an
      important risk factor for both the acquisition and transmission of HIV.

PMID- 16406035
TI  - The economic burden of visceral leishmaniasis for households in Nepal.
AB  - Visceral leishmaniasis (VL) affects persons from the lowest socioeconomic strata
      of the community, but its economic impact is not precisely known. An exploratory
      survey to document the economic costs of VL to households was conducted in an
      endemic focus in eastern Nepal. Data were collected from the 20 households in
      this cluster. Cases of VL over the last 3 years were elicited and information on
      direct and indirect costs incurred due to the disease as well as income of the
      households over the last year was estimated. It was reported that 15.0% (16/107)
      of the residents had suffered from VL and that almost all of the patients had
      preferred, in the first instance, to visit the private services or local faith
      healers instead of visiting the local public health facility. Average total costs
      incurred per episode of VL were above the median annual per capita income, and
      six of the seven affected households either had to sell part of their livestock
      or to take a loan to cover the costs. Direct costs consisted of 53% of the total
      cost, with 75% of this cost incurred before the patients actually received any
      treatment for VL. This study demonstrates how VL can lead to catastrophic
      expenditure for affected households.

PMID- 16406036
TI  - Inorganic particles in the skin of inhabitants of volcanic areas of Central
      America: their possible immunomodulatory influence in leishmaniasis and leprosy.
AB  - We have evaluated biopsies from patients with atypical nodular and typical
      ulcerated lesions of cutaneous leishmaniasis, from leishmanin reactions and skin
      from normal individuals from Nicaragua, Honduras and Guatemala for the presence
      of inorganic particles using confocal microscopy with a polarised light source
      and conventional histopathological techniques. Analysis by semiquantitative
      confocal microscopy permitted the demonstration of significantly larger numbers
      of particles in atypical lesions. Silica and aluminium, important components of
      these particles, were less abundant in particles from normal skin. The histology
      of these atypical lesions, characterised by 'naked' sarcoidal granulomas with
      epithelioid differentiation but very few lymphocytes, was very similar to the
      histological reaction observed after 14 days in persisting inflammation at
      leishmanin skin test sites. The presence of these unusual lesions in areas of
      Central American countries characterised by the presence of large amounts of
      volcanic ash, as well the unexpectedly low prevalence of leprosy in Central
      America, suggest that environmental factors may contribute significantly to the
      frequency and clinical manifestations of these infections. Among possible
      environmental features, the presence of inorganic particles with immunomodulatory
      properties in the skin may be a significant factor.

PMID- 16406037
TI  - Spatiotemporal patterns of malaria incidence in northern Thailand.
AB  - We present a detailed analysis of long-term time series of malaria incidence in
      northern Thailand. Positive cases for Plasmodium falciparum and P. vivax have
      been recorded monthly from 1977-2002 at 13 provinces in the region. Time series
      statistical methods are used to examine the long-term trends and seasonal
      dynamics of malaria incidence at regional and provincial scales. Both malarial
      types are declining throughout the region, except in the two provinces that share
      a large border with Myanmar. The rate of decline in P. vivax has decreased across
      the region since the end of the 1980s, and this may be a signal of developing
      resistance or changing vector potential. Both species display a two-peak annual
      seasonality that may be attributed to patterns of vector occurrence, farming
      practice and migration of individuals across international borders. In a number
      of provinces, the importance of the first seasonal peak has grown in recent
      years, possibly owing to increases in vector densities. The medium-term
      fluctuations of both species exhibit a clear spatial organisation. There is some
      evidence of a subtle close to 4-year super annual cycle in P. falciparum, which
      we suggest is driven by extrinsic factors relating to the climate of the region.

PMID- 16406038
TI  - Teneurins: a conserved family of transmembrane proteins involved in intercellular
      signaling during development.
AB  - Teneurins, which were initially described as ten-a and the pair-rule gene ten
      m/odz in Drosophila, are a family of highly conserved proteins that have recently
      been characterized in Caenorhabditis elegans and a number of vertebrates. We have
      proposed the nomenclature teneurin 1-4 for the four members of this gene family
      found in vertebrates. Recent evidence shows that teneurins belong to a novel
      class of signaling molecules that function both at the cell surface as type II
      transmembrane receptors and, after the release of the intracellular domain, as
      transcriptional regulators. Nuclear localization of the intracellular domain has
      been observed in vitro in mammalian cells and confirmed in vivo in C. elegans.
      RNAi studies and mutational analysis has revealed that Ten-1 in C. elegans is an
      important regulator of many aspects of morphogenesis, including germ cell
      development and neuronal pathfinding. In vertebrates, teneurins are concentrated
      in the developing and adult central nervous system and at sites of pattern
      formation, including the developing limb. Teneurins also possess a carboxy
      terminal sequence that may be processed to generate a neuromodulatory peptide.
      Teneurin function appears to be required for a fundamentally important signaling
      mechanism conserved between invertebrates and vertebrates having an impact on
      many processes relying on cell-cell contact throughout development.

PMID- 16406039
TI  - Defective postnatal development of the male reproductive tract in LGR4 knockout
      mice.
AB  - The final outcome of tube elongation and branching is to maximize the epithelial
      exchange surfaces in tubular organs. The molecular and cellular basis of these
      processes is actively studied in model organs such as mammary glands, liver and
      kidney, but they remain almost unexplored in the male reproductive tract. Here,
      we report that the orphan G protein-coupled receptor LGR4/GPR48 plays a role in
      the postnatal tissue remodeling needed for elongation and convolution of the
      efferent ducts and epididymis. In LGR4 knockout male mice, tube elongation fails,
      resulting in a hypoplastic and poorly convoluted tract. Cell proliferation is
      dramatically reduced in KO affected tissues, providing an explanation to the
      observed phenotype. Detailed analysis showed that LGR4 inactivation manifests
      differently in the affected organs. In efferent ducts, immune cells infiltrate
      the epithelium and reach the lumen, blocking the transit of sperm and testicular
      fluid. In addition, the hypoplasia and low convolution result in a reduction of
      the epithelial area involved in liquid reabsorption. Both phenomena contribute in
      tissue swelling upstream the blockade due to liquid and sperm accumulation, with
      secondary damaging effects on the germinal epithelium. In the epididymis, the
      thin and highly convoluted duct is replaced by a large cystic tube which is
      surrounded by a thick condensation of mesenchymal cells. The abnormal
      organization of the cellular compartments in and around the ducts suggests that
      LGR4 might play a role in epithelial-mesenchymal interactions. Altogether, our
      data identify LGR4 as an important signaling molecule implicated in the tube
      morphogenesis of the male reproductive tract.

PMID- 16406040
TI  - A modification of the Harper-McGinty microdrive for use in chronically prepared
      rabbits.
AB  - We describe a modification of the Harper-McGinty microdrive for use with
      extracellular, microwire recording in conscious, chronically prepared rabbits.
      Improvements over existing designs are in ease of assembly and mechanical
      stability. The microdrive is easily fabricated with hand tools and readily
      available parts. In addition, assembly of the microdrive utilizes epoxy, avoiding
      the difficult task of soldering stainless steel parts. Finally, the microdrive is
      mounted directly to the skull enhancing mechanical stability and eliminating the
      need to allow space for screw travel. Importantly, this microdrive has proven to
      be durable as well as functional in our preparation.

PMID- 16406041
TI  - A novel technique to quantify glioma tumor invasion using serial microscopy
      sections.
AB  - Here we present a new technique to quantitatively characterize malignant glioma
      invasion in a syngeneic mouse model. The GL261 mouse malignant glioma cell line
      was injected intracerebrally into the C57B1/6 black mouse and allowed to
      propagate for 10 or 17 days, followed by euthanasia of the animal, harvesting of
      the brain, fixation, and serial sectioning. Histologic examination was performed
      and the primary tumor mass and discontinuous sites of tumor invasion were traced
      on digital images of serial microscopy sections, followed by analysis of the
      invasion characteristics using a custom-written MATLAB program. We found a
      significant increase in the number of discontinuous tumor invasion sites and in
      the distance of these sites from the tumor centroid in mice that were euthanized
      at 17 days post-tumor cell injection, as compared to mice euthanized at 10 days.
      Furthermore, a scatter plot analyses indicated that the invasion site data could
      be grouped based on the characteristics of area and distance from the tumor
      centroid to reveal significant differences between the two experimental groups of
      mice. This quantitative method will allow a future in vivo analysis of invasion
      characteristics in glioma cells expressing altered levels or function of invasion
      genes, and of new therapy targeting invading glioma cells.

PMID- 16406042
TI  - Improved methods for ultracryotomy of CNS tissue for ultrastructural and
      immunogold analyses.
AB  - We examined each step of the protocol for ultracryotomy for central nervous
      system tissue in order to define and overcome some of the methodological
      difficulties. The following three steps emerged as critical for the method's
      success: (1) pretreatment of grids to render them hydrophilic immediately before
      use; (2) careful collection of ultrathin cryosections during ultracryotomy; (3)
      removal of the appropriate amount of excess poly(vinyl alcohol)-uranyl acetate
      (PVA-UA) prior to drying after staining with PVA-UA. By taking account of the
      three critical steps described above, we succeeded in obtaining ultrathin
      cryosections, including serial sections, with excellent preservation of
      ultrastructure, as well as semithin cryosections which are useful for evaluating
      the quality of the samples and for selecting areas of interest for
      ultrastructural analysis. Cytoplasmic organelles in neurons and glial cells, and
      the fine structure of synapses and myelinated fibers were well preserved. The
      localization of gold particles after immunostaining for astrocytic glutamate
      transporter (GLAST), metabotropic glutamate receptor 1 (mGluR1) and neurofilament
      protein was consistent with previous reports and ultrastructure was well
      preserved in all cases. These findings should be helpful to researchers wishing
      to carry out ultrastructural and immunogold analyses of cryosections of nervous
      tissue.

PMID- 16406043
TI  - Murine auditory brainstem evoked response: putative two-channel differentiation
      of peripheral and central neural pathways.
AB  - Standard noninvasive recordings of the auditory brainstem evoked response (ABR)
      from a single pair of obliquely oriented electrodes (typically midline vertex
      referenced to mastoid) confound inherently distinct signals propagating over
      peripheral and central neural pathways differing in location and spatial
      orientation. We describe here a technique for recording short-latency auditory
      evoked potentials that putatively differentiates peripheral and central neural
      activity in the mouse and rat. The technique involves recording from two
      orthogonally oriented electrode pairs using fast sample rates (100 k/s) to
      accurately measure differences in neural timing and waveform morphology.
      Electrodes oriented in a transverse plane (mastoid-to-mastoid) register an
      initial positive-going ABR peak (P1T) earlier than a series of peaks recorded
      from electrodes oriented along the midline (anterior and posterior to the inter
      aural line). The absolute P1T latency is consistent with an origin in the primary
      auditory nerve, while the delayed midline latencies implicate activity farther
      along central neural pathways. Differences between these latencies (midline minus
      transverse) provide new and precise measures of central conduction time (CCT),
      which in one case is as brief as 0.10 ms. Results in wild type (WT) and knockout
      (KO) mice, as well as rats, show significant differences in absolute latencies as
      well as CCT.

PMID- 16406044
TI  - The co-evolution of intergenerational transfers and longevity: an optimal life
      history approach.
AB  - How would resources be allocated among fertility, survival, and growth in an
      optimal life history? The budget constraint assumed by past treatments limits the
      energy used by each individual at each instant to what it produces at that
      instant. We consider under what conditions energy transfers from adults, which
      relax the rigid constraint by permitting energetic dependency and faster growth
      for the offspring, would be advantageous. In a sense, such transfers permit
      borrowing and lending across the life history. Higher survival and greater
      efficiency in energy production at older ages than younger both favor the
      evolution of transfers. We show that if such transfers are advantageous, then
      increased survival up to the age of making the transfers must co-evolve with the
      transfers themselves.

PMID- 16406045
TI  - Protective effect of donepezil in primary-cultured rat cortical neurons exposed
      to N-methyl-d-aspartate (NMDA) toxicity.
AB  - Donepezil has a neuroprotective effect against oxygen-glucose deprivation injury
      and glutamate toxicity in cultured cortical neurons. In this study, we further
      characterized the neuroprotective properties of donepezil in rat cortical cell
      cultures using glutamate receptor-specific agonists (N-methyl-d-aspartate (NMDA),
      alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate).
      Pretreatment with donepezil (1 microM) for 12 h significantly decreased the
      lactate dehydrogenase (LDH) release in response to NMDA (100 microM) by 43.8%,
      and reduced the LDH release in response to kainate (100 microM) and AMPA (100
      microM) by 11.9% and 7.5% (without statistical significance), respectively.
      Donepezil appeared to inhibit LDH release in a concentration-dependent manner at
      0.1-10 microM. Cortical neurons exposed to NMDA retained a normal morphological
      appearance in the presence of 10 microM donepezil. In binding assay for glutamate
      receptors, donepezil at 100 microM only slightly inhibited binding to the glycine
      and polyamine sites on NMDA receptor complex. On the other hand, 12 h
      pretreatment with donepezil at 10 and 100 microM significantly decreased the NMDA
      induced increase of intracellular calcium concentration ([Ca2+]i). In conclusion,
      our results show that donepezil has protective activity against NMDA toxicity in
      cortical neurons, and this neuroprotection seems to be partially mediated by
      inhibition of the increase of [Ca2+]i.

PMID- 16406046
TI  - Suicidal ideation and suicidal attempts in a population-based study of Chinese
      people: risk attributable to hopelessness, depression, and social factors.
AB  - BACKGROUND: The population attributable fraction of hopelessness, depression and
      other risk factors for suicidal ideation and suicidal attempts in Asian
      population is unknown. Social support is often said to be a buffer against the
      effect of hopelessness and depression. METHODS: Suicidal ideation, suicidal
      attempts as well as demographic and psychometric data were delineated in a random
      and representative population sample of 2,219 Chinese people in Hong Kong. The
      population attributable fraction was used to determine the contribution of
      hopelessness, depression and other risk factors to suicidal ideation and
      attempts. RESULTS: Multivariate modelling shows that about 40% of suicidal
      ideation and attempts was attributable to depression and about 20% was
      attributable to hopelessness. Drug abuse and marital dissolution were also
      significant contributors to suicidality. The impact of hopelessness and
      depression was not affected by social support. LIMITATIONS: Suicidality was self
      reported. CONCLUSIONS: Suicidal ideation and suicidal attempts were to a large
      extent attributable to depression and hopelessness, and, to a lesser extent, drug
      abuse and marital dissolution. Social support appeared to play little role as a
      buffer.

PMID- 16406047
TI  - CD8 T cell effector maturation in HIV-1-infected children.
AB  - HIV-1 infection generates maturational responses in overall CD4 and CD8 T cell
      populations in adults, with elevated expression of lytic effector molecules
      perforin and granzyme B, and reduced expression of CCR7 and CD45RA. Here, we have
      found that these marked effects were significantly less pronounced in children,
      both in terms of the skewed CCR7/CD45RA expression profile as well as the
      increased perforin expression. Similar to adults, HIV-specific CD8 cells in
      children were largely CD27+ CD45RA- and lacked perforin. However, one pediatric
      subject with late-stage infection displayed robust expansion of Gag 77-85
      specific CD8 T cells which were perforin+ and lytic, but lacked expression of
      CD27 and IFNgamma. Our data indicate that the T cell effector maturation induced
      by HIV-1 infection is markedly weaker in children as compared to adults. The data
      also suggest, however, that the perforin-deficient state of HIV-specific CD8 T
      cells in children may be reversible.

PMID- 16406048
TI  - Neural-cell adhesion molecule (NCAM) expression by immature and tumor-derived
      endothelial cells favors cell organization into capillary-like structures.
AB  - The neural cell adhesion molecule (NCAM) is widely expressed during
      embryogenesis, down-regulated in the course of differentiation to be re-expressed
      during progression of some tumors. We here found that renal tumor-derived
      endothelial cells (TEC) but not normal endothelial cells (HMEC) expressed NCAM.
      In TEC, NCAM expression was regulated by the renal embryonic transcription factor
      PAX2, as transfection with PAX2 antisense abrogated NCAM expression. NCAM
      stimulation with an agonistic synthetic NCAM peptide enhanced apoptosis
      resistance and increased ability of TEC to organize in vessel-like structures.
      The angiogenic effect of NCAM peptide was, at least in part, mediated by the
      association of NCAM and FGFR1. HMEC transiently acquired NCAM when organized in
      vessel-like structures after VEGF stimulation or when transfected with PAX2 gene.
      During the process of VEGF-induced endothelial differentiation of renal stem
      cells and of circulating endothelial progenitors, NCAM was transiently expressed
      to disappear at complete endothelial maturation. Targeting NCAM with a saporin
      conjugated peptide induced a cytotoxic effect on TEC but not on HMEC. In
      conclusion, we identified a new role of NCAM in tumor neo-angiogenesis relevant
      for endothelial cell organization into capillary-like structures. In addition, we
      found that NCAM expression was associated with an immature phenotype of
      endothelial cells.

PMID- 16406049
TI  - Hardness and carbonate effects on the reactivity of zero-valent iron for Cr(VI)
      removal.
AB  - Zero-valent iron (Fe0) was used to remove hexavalent chromium, Cr(VI), in
      groundwater via a coupled reduction-oxidation reaction. Nine columns were set up
      under various groundwater geochemistry to investigate the effects of hardness and
      carbonate on Cr(VI) removal. The Cr(VI) removal capacity of Fe0 was found to be
      about 4 mgCr/g Fe0 in the control column (i.e., column 1). A slight decrease in
      the Cr(VI) removal capacity was found in the presence of calcium hardness.
      However, there was a 17% drop in the Cr(VI) removal capacity when magnesium
      hardness was present at low to moderately hard level. Results also revealed that
      carbonate changed the morphology of the Fe0 by formation of pale green
      precipitates on the iron filings. Furthermore, there was a 33% decrease in the
      Cr(VI) removal capacity of Fe0 when both carbonate and hardness ions were
      present. In general, the presence of hardness ions and carbonate in groundwater
      have great impact on the Fe0 by formation of passivated precipitates, such as
      CaCO3, on the Fe0 surface resulting in a diminished lifespan of the Fe0 by
      blocking electron transfer.

PMID- 16406050
TI  - Endocannabinoid, anandamide in gingival tissue regulates the periodontal
      inflammation through NF-kappaB pathway inhibition.
AB  - Anandamide (AEA) exhibits anti-inflammatory effects. However, its role in the
      periodontal field remains unknown. Here, we found that gingival crevicular fluid
      contained a detectable level of AEA. The cannabinoid receptors CB1 and CB2 were
      expressed by human gingival fibroblasts (HGFs), and markedly upregulated under
      pathological conditions. AEA significantly reduced the production of pro
      inflammatory mediators (IL-6, IL-8 and MCP-1) induced by Porphyromonas gingivalis
      LPS in HGFs, and this effect was attenuated by AM251 and SR144528, selective
      antagonists of CB1 and CB2, respectively. Moreover, AEA completely blocked LPS
      triggered NF-kappaB activation, implying that AEA may regulate hyperinflammatory
      reactions in periodontitis.

PMID- 16406051
TI  - Exposure to polychlorinated biphenyls in residents near a chemical factory in
      Italy: the food chain as main source of contamination.
AB  - High levels of PCBs were recently found in soil, food and some farmers living
      close to a chemical factory which until the 1980s had produced polychlorinated
      biphenyls (PCBs) in Brescia, North Italy. We performed a survey on a random
      sample of subjects aged 20-79 years living in various areas of the town with
      different levels of soil pollution to investigate factors associated with
      increased levels of PCB in serum (24 congeners were tested). Total PCB values
      were closely related to age (Spearman r=0.68; p<0.0001). The 166 consumers of
      locally produced food had higher PCB levels than non-consumers (median=1143
      versus 719; 95th centile=9301 versus 2635ng/g lipid) with the highest levels
      among consumers of food produced in the most contaminated area close to the
      factory (median=2551; 95th centile=33464ng/g lipid). A dose-effect relationship
      between consumption of food produced in this area and PCB blood levels was
      observed (Spearman r=0.52, p=0.0014). Consumers of only plant food produced in
      this area had higher levels of PCB than non-consumers (median=1100; 95th
      centile=10,800ng/g lipid). Three subjects who had worked at the factory in the
      past showed high PCB levels. Distribution of PCB congeners did not differ between
      consumers of locally produced food and non-consumers, apart from PCB 209 which
      was found at high levels in former factory workers and was more common among
      consumers of food produced in the polluted area. In conclusion, we found high
      serum PCB levels in humans living in a highly polluted area in an industrialized
      town in Italy, due mainly to consumption of food produced in polluted areas.

PMID- 16406052
TI  - In situ bioelectrokinetic remediation of phenol-contaminated soil by use of an
      electrode matrix and a rotational operation mode.
AB  - In situ bioremediation is a safe and cost-effective technology for the cleanup of
      contaminated sites, but its remediation rate is usually very slow. This study
      attempted to accelerate the process of bioremediation by employing non-uniform
      electrokinetic transport processes to mix organic pollutants and degrading
      bacteria in soils under in situ conditions (namely, in situ bioelectrokinetic
      remediation) by use of an electrode matrix and a rotational operation mode. A
      bench-scale non-uniform electrokinetic system with periodic polarity-reversal was
      developed for this purpose, and tested by using a sandy loam spiked with phenol
      as a model organic pollutant. The results demonstrated that non-uniform
      electrokinetic processes could enhance the in situ biodegradation of phenol in
      the soil, the efficiency of which depended upon the operational mode of the
      electric field. Compared with the unidirectional operation and the bidirectional
      operation, the rotational operation could effectively stimulate the
      biodegradation of phenol in the soil if adopting appropriate time intervals of
      polarity-reversal and electrode matrixes. A reversal interval of 3.0 h and a
      square-shaped electrode matrix with four electrode couples appeared appropriate
      for the in situ biodegradation of phenol, at which a maximum phenol removal of
      58% was achieved in 10d and the bioremediation rate was increased about five
      times as compared to that with no electric field applied. The results also showed
      that adopting a small polarity-reversal interval and an appropriate electrode
      array could produce a high and uniform removal of phenol from the soil. It is
      believed that in situ bioelectrokinetic remediation holds the potential for field
      application.

PMID- 16406053
TI  - Toxicity of three halogenated flame retardants to nitrifying bacteria, red clover
      (Trifolium pratense), and a soil invertebrate (Enchytraeus crypticus).
AB  - Halogenated flame retardants have a high sorption affinity to particles, making
      soils and sediments important sinks. Here, three of the most commonly used flame
      retardants have been tested for sub-lethal toxicity towards soil nitrifying
      bacteria, a terrestrial plant (seed emergence and growth of the red clover,
      Trifolium pratense), and a soil invertebrate (survival and reproduction of
      Enchytraeus crypticus). Tetrabromobisphenol A (TBBPA) was quite toxic to
      enchytraeids, with significant effects on reproduction detected already at the 10
      mgkg(-1) exposure level (EC(10)=2.7 mgkg(-1)). In contrast, decabromodiphenyl
      ether (DeBDE) was not toxic at all, and short-chain chloroparaffins (CP(10-13))
      only affected soil nitrifying bacteria at the highest test concentration
      (EC(10)=570 mgkg(-1)). Exposure concentrations were verified by chemical analysis
      for TBBPA and DeBDE, but not for CP(10-13), as a reliable method was not
      available. Based on the generated data, a PNEC for soil organisms can be
      estimated at 0.3 mgkg(-1) for TBBPA and 57 mgkg(-1) for short-chain
      chloroparaffins. No PNEC could be estimated for DeBDE. Measurements of TBBPA in
      soil are not available, but measured concentrations in Swedish sludge are all
      lower than the estimated threshold value for biological effects in soil.

PMID- 16406054
TI  - Effects of photodegradation of dissolved organic matter on the binding of
      benzo(a)pyrene.
AB  - Dissolved organic matter (DOM) in natural waters can bind various organic
      pollutants, and the affinity of this binding is strongly influenced by the
      chemical characteristics of the DOM and water pH. This study examined the effects
      of photochemically induced alteration of the DOM's chemical properties and water
      pH on the binding of benzo(a)pyrene (BaP). Time- and pH-series of solar-simulated
      irradiations were performed on a natural water sample and aqueous DOM solutions
      prepared from aquatic and soil humic substances. The binding affinity of BaP,
      expressed as a partition coefficient of a compound to DOM, decreased
      substantially after the DOM samples were irradiated over environmentally relevant
      radiation doses and pH ranges. The lowering of the pH due to the photoproduction
      of acidic products often partly offsets the reduction of the binding affinity
      caused by direct photoalteration of the DOM's chemical structure. The decrease of
      the binding affinity, after correction for the photoinduced pH change, was
      positively correlated with the decrease in the molecular weight and the
      aromaticity of the DOM in the course of irradiation. Increasing O(2) abundance
      accelerated the decrease of the binding affinity as a result of enhanced DOM
      photodegradation. Visible light played a more important role in reducing the
      molecular weight and aromaticity of the DOM than in reducing the content of
      dissolved organic carbon (DOC) via photoremineralization while the reverse was
      true for UV radiation, indicating that photochemical reduction of the binding
      affinity may occur in natural waters at depths greater than UV radiation can
      reach. A decrease of the affinity of DOM for binding BaP will increase the free
      dissolved fraction of BaP and thus its availability and toxicity to aquatic
      organisms. The results from this study may have similar implications for organic
      pollutants other than BaP.

PMID- 16406055
TI  - Soil screening for identifying ecological risk stressors using a battery of in
      vitro cell bioassays.
AB  - Soil screening could be a process of identifying and defining areas,
      contaminants, and condition at the sites that warrant further attention for
      developing ecological risk assessments. In present work, a total of 41 surface
      soil samples from Tianjin, China were sampled and the soil organic extracts were
      evaluated using a battery of in vitro cell bioassays. The battery included
      ethoxyresorfin O-deethylase (EROD) with H4IIE rat hepatoma cells bioassay for
      Aryl hydrocarbon (Ah) receptor (Ah-agonists) effects, the SOS/umu bioassay for
      genotoxic effects, and human estrogen receptor recombinant yeast bioassay for
      estrogenic effects. The results have showed that total estrogenic effects in
      these soil samples was measured to be between 0.1 and 14.2ng EEQkg(-1) soil
      (d.w.); Ah-agonists effects assayed by EROD bioassay varied from 2.8ng TEQkg(-1)
      soil (d.w.) to 42.6ng TEQkg(-1) soil (d.w.), and the amounts of soil weight
      required for the extracts to lead positive result (IR 2.0) in the SOS/umu
      bioassay were between 3.9 and 31.3mg (d.w.) per well. In addition, the geographic
      distributions of Ah-agonists effects and genotoxic effects in Tianjin area
      exhibited a strong positive correlation with each other. However, the
      distribution of estrogenic effects with high levels in northwest Tianjin was
      markedly different from that of Ah-agonists effects, where the high levels were
      distributed in the urban of Tianjin, as well as coastal towns. It has been
      concluded that the toxicity assessment of surface soil using a battery of in
      vitro cell bioassays could provided meaningful information regarding
      characterization procedure in ecological risk assessment.

PMID- 16406056
TI  - Prolactin and growth hormone in fish osmoregulation.
AB  - Prolactin is an important regulator of multiple biological functions in
      vertebrates, and has been viewed as essential to ion uptake as well as reduction
      in ion and water permeability of osmoregulatory surfaces in freshwater and
      euryhaline fish. Prolactin-releasing peptide seems to stimulate prolactin
      expression in the pituitary and peripheral organs during freshwater adaptation.
      Growth hormone, a member of the same family of hormones as prolactin, promotes
      acclimation to seawater in several teleost fish, at least in part through the
      action of insulin-like growth factor I. In branchial epithelia, development and
      differentiation of the seawater-type chloride cell (and their underlying
      biochemistry) is regulated by GH, IGF-I, and cortisol, whereas the freshwater
      type chloride cell is regulated by prolactin and cortisol. In the epithelia of
      gastrointestinal tract, prolactin induces cell proliferation during freshwater
      adaptation, whereas cortisol stimulates both cell proliferation and apoptosis. We
      propose that control of salinity acclimation in teleosts by prolactin and growth
      hormone primarily involves regulation of cell proliferation, apoptosis, and
      differentiation (the latter including upregulation of specific ion transporters),
      and that there is an important interaction of these hormones with
      corticosteroids.

PMID- 16406057
TI  - Local immunity in Indian women with bacterial vaginosis.
AB  - OBJECTIVES: To determine the immunoglobulin (Ig) and cytokine levels and
      degradation of Igs in the cervico-vaginal secretions (CVS) of non-pregnant Indian
      women of low socio economic status (LSES), with/without bacterial vaginosis (BV)
      and to assess the interactions among nutritional status, BV and local immunity.
      METHODS: A descriptive study in non-pregnant women of LSES attending the
      gynecology out patient clinic at a local government hospital, Hyderabad, India.
      Two hundred non-pregnant women underwent clinical, anthropometrical and
      gynecological examination and were screened for BV. In a sub-sample of 80
      with/without BV, levels of IL-10 and IL-12, IgA, IgM and IgG were determined in
      the CVS by ELISA and degradation of IgA and IgM by Western blotting. Statistical
      significance among the groups was tested using the non-parametric Mann-Whitney U
      test. RESULTS: Fifty seven percent of the women tested positive for BV. Women
      with BMI<16.0 had the highest BV positivity and the lowest IgA levels in CVS.
      Higher levels of IgA were observed in women with BMI>18.5. There was significant
      degradation of IgA and IgM in women with BV. IL-12 was undetectable while IL-10
      was detected with higher means in CVS of women with BV. CONCLUSIONS: Severe under
      nutrition appears to be relevant to BV positivity and local immunity in these
      women. Greater degradation of IgA and IgM in BV suggests impaired local immunity.

PMID- 16406058
TI  - Identification of tidal and climatic influences within domestic radon time-series
      from Northamptonshire, UK.
AB  - Analysis of data from extended radon concentration time-series obtained from
      domestic and public-sector premises in the vicinity of Northampton, UK, and
      elsewhere, confirms that, in addition to the generally recognised climatic
      influences, 'Earth Tides' and 'Ocean Tidal Loading' drive periodic radon
      liberation via geophysically driven groundwater level variations. Regression and
      cross-correlation with environmental parameters showed some degree of association
      between radon concentration and mean temperature and rainfall. Fourier analysis
      of radon time-series identified periodicities of the order of 23.9 h (luni-solar
      diurnal, K(1)), 24.0 h (solar day, S(1)), 168 h (1 week) and 661.3 h (lunar
      month, M(m)), while cross-correlation with tidal strength demonstrated
      periodicity of the order of 14 days (lunar-solar fortnight, M(f)). These results
      suggest that astronomical influences, including tides, play a part in controlling
      radon release from the soil.

PMID- 16406059
TI  - Suppression of non-specific binding in serological Luminex assays.
AB  - Bead-based suspension array technology (xMAP, Luminex Corp.) permits the
      simultaneous analysis of antibodies with specificities for up to 100 different
      antigens in a single reaction and the high through-put screening of up to 1,000
      sera per day. Therefore, this technology is becoming more and more popular for
      serological analyses, replacing ELISA techniques at least for epidemiological
      purposes. However, a major intrinsic problem of Luminex technology is that human
      sera may contain antibodies that directly bind to the beads, resulting in
      intolerably high non-specific background. The proportion of such "bead binders"
      in different serum panels frequently exceeds 5% and is therefore a severe
      problem. We screened for background inhibitors and found that serum pre
      incubation with polyvinylalcohol, polyvinylpyrrolidone and a proprietary reagent
      (Super ChemiBlock, Chemicon) significantly reduced non-specific background,
      whereas use of Luminex SeroMap beads only partially solved the problem.

PMID- 16406060
TI  - Oxygen tension regulates the in vitro maturation of GM-CSF expanded murine bone
      marrow dendritic cells by modulating class II MHC expression.
AB  - Conventional culture conditions for GM-CSF expanded murine bone marrow derived
      dendritic cells (BMDCs) uses ambient (hyperoxic) oxygen pressure (20% v/v, 152
      Torr) and medium supplemented with the thiol 2-mercaptoethanol (2-Me). Given the
      redox activities of O2 and 2-Me, the effects of 2%, 5%, 10%, and 20% v/v O2
      atmospheres and omitting 2-Me from the medium were tested upon the generation of
      GM-CSF expanded BMDCs. DC yield, phenotype and function were compared to BMDCs
      grown using conventional conditions. All cultures yielded DC subsets with CD11c+
      MHC II(NEG), CD11c+ MHC II(INT), CD11c+ MHC II(HI) expression phenotypes, classed
      as precursor, immature, and mature DCs (IDC, MDC). Low O2 tensions generated
      significantly fewer precursor DCs, and more IDCs and MDCs. Cytometer sorted
      precursor DCs expressed surface class II MHC after transfer to low, but not high
      O2 atmospheres. Expression of myeloid markers was similar between BMDC cultures
      generated in 5% O2 or conventional conditions, and MDCs from low O2 cultures had
      the morphology typical of mature myeloid DCs. IDCs and MDCs from low O2 and
      conventional culture conditions were similarly potent allostimulatory APCs. The
      O2 tension (but not 2-Me addition) in vitro significantly influences overall DC
      subset frequencies and yield, and governs DC maturation by regulating the surface
      class II MHC expression of GM-CSF expanded BMDC cultures.

PMID- 16406061
TI  - The SH2 domain-containing inositol 5-phosphatase SHIP1 is recruited to the
      intracytoplasmic domain of human FcgammaRIIB and is mandatory for negative
      regulation of B cell activation.
AB  - Murine FcgammaRIIB were demonstrated to recruit SH2 domain-containing inositol 5
      phosphatases (SHIP1/2), when their ITIM is tyrosyl-phosphorylated upon co
      aggregation with BCR, and SHIP1 to account for FcgammaRIIB-dependent negative
      regulation of murine B cell activation. Although human FcgammaRIIB share the same
      ITIM as murine FcgammaRIIB and similarly inhibit human B cell activation, which
      among the four known SH2 domain-containing (tyrosine or inositol) phosphatases
      is/are recruited by human FcgammaRIIB is unclear. Our recent finding that,
      besides the ITIM, a second tyrosine-based motif is mandatory for murine
      FcgammaRIIB to recruit SHIP1 challenged the possibility that human FcgammaRIIB
      recruit this phosphatase. Human FcgammaRIIB indeed lack this motif. Using an
      experimental model which enabled us to compare human FcgammaRIIB and murine
      FcgammaRIIB under strictly controlled conditions, we show that SHIP1 is recruited
      to the intracytoplasmic domain of human FcgammaRIIB and inhibits the same
      biological responses and intracellular signals as when recruited by murine
      FcgammaRIIB. Identical results were observed in murine and in human B cells. We
      demonstrate that SHIP is necessary for human FcgammaRIIB to inhibit BCR
      signaling, and cannot be replaced by SHP-1 or SHP-2. Although it contains no
      tyrosine, the C-terminal segment of human FcgammaRIIB was as mandatory as the
      tyrosine-containing C-terminal segment of murine FcgammaRIIB for SHIP1 to be
      recruited to the ITIM. This segment, however, did not recruit the adapters
      Grb2/Grap which were demonstrated to stabilize the recruitment of SHIP1 to the
      ITIM in murine FcgammaRIIB.

PMID- 16406062
TI  - Residual pelvic lymph node involvement after concomitant chemoradiation for
      locally advanced cervical cancer.
AB  - OBJECTIVE: Concomitant chemoradiation (and brachytherapy) has become the standard
      treatment for locally advanced cervical cancers (FIGO stage IB2 to IVA). Adjuvant
      surgery is optional. The aim of this study was to evaluate the rate of residual
      positive pelvic lymph nodes after chemoradiation. METHODS: From February 1988 to
      August 2004, 113 patients with locally advanced cervical cancer have been treated
      by chemoradiation followed by an adjuvant surgery with a pelvic lymphadenectomy
      performed (study group). A para-aortic lymphadenectomy had also been performed in
      85 of them. RESULTS: The mean age of the patients was 48.4 years (27-74). FIGO
      stage was: IB2 in 17.7% (20/113), II in 44.2% (50/113), III in 21.2% (24/113) and
      IVA in 16.8% of the patients (19/113). The mean number of removed nodes was 11.5
      (median 11) in pelvic, and 7.5 (median 7) in para-aortic basins. A pelvic lymph
      node involvement was present in 15.9% (18/113) of the patients after
      chemoradiation. In 11 patients, only one node was positive. 11.7% (10/85) of the
      patients had a para-aortic lymph node involvement. A residual pelvic lymph node
      disease has been observed in 6.3% (4/63) of the cases with no residual cervical
      disease (or microscopic) versus 26.5% (13/49) of the cases with macroscopic
      residual cervical tumor (P = 0.003). CONCLUSIONS: Our experience shows that a
      pelvic lymph node involvement persists in about 16% of the patients after
      chemoradiation. We can make the assumption that performing a pelvic
      lymphadenectomy along with the removal of the primary tumor after chemoradiation
      could reduce the rate of latero-pelvic recurrences, whatever the para-aortic
      lymph node status.

PMID- 16406063
TI  - Pelvic lymph node count is an important prognostic variable for FIGO stage I and
      II endometrial carcinoma with high-risk histology.
AB  - OBJECTIVE: To determine whether pelvic lymph node count is associated with
      patterns of recurrence or survival in patients with FIGO stage I and II
      endometrial cancer. METHODS: Single institution retrospective study of 467
      patients with FIGO stage I and II endometrial cancer treated with primary surgery
      including lymph node dissection. Analysis included pelvic lymph node count,
      histology, stage, age, race, BMI, year of surgery, depth of myometrial invasion,
      and adjuvant radiation. Kaplan-Meier life-tables were used to calculate survival;
      the Cox proportional hazards model was used to identify prognostic factors
      independently associated with survival. RESULTS: Mean pelvic lymph node count was
      12.6 (SD +/- 8). Distant recurrence was associated with decreased pelvic lymph
      node count, high-risk histology, and postoperative pelvic radiation. Pelvic lymph
      node count was not associated with survival by univariate analysis, however,
      overall (OS) and progression-free (PFS) survival were significantly better with
      pelvic lymph node counts >or=12 among women with high-risk histology (P < 0.001),
      but not among women with low-risk histology. Multivariable Cox proportional
      hazards regression identified increasing age, non-Caucasian race, and high-risk
      histology as independent negative prognostic factors for both OS and PFI. Among
      patients with high-risk histology, pelvic lymph node count remained an
      independent prognostic factor for both overall (OS) and progression-free survival
      (PFS) in the model, with hazard ratios of 0.28 and 0.29, respectively, when
      >or=12 pelvic lymph nodes were identified. Pelvic lymph node count had no
      association with OS or PFS in women with low-risk histology. CONCLUSION: Pelvic
      lymph node count >or=12 is an important prognostic variable in patients with FIGO
      stage I and II endometrial cancer who have high-risk histology. Most likely, the
      association of survival and lymph node count in this group is the result of
      improved staging among patients with higher pelvic lymph node counts.

PMID- 16406064
TI  - Effectiveness of darbepoetin alfa versus epoetin alfa for the treatment of
      chemotherapy induced anemia in patients with gynecologic malignancies.
AB  - OBJECTIVE: Chemotherapy induced anemia (CIA) commonly occurs in gynecologic
      oncology patients. This often leads to treatment with erythropoietic stimulating
      agents in order to prevent chemotherapy delays, dose modifications and
      transfusion of red blood cells. Our objective was to determine the subsequent
      transfusion rates following administration of either darbepoetin alfa or epoetin
      alfa. METHODS: A single institution retrospective chart review was performed
      utilizing patients from January 2003 to September 2004 who received either
      darbepoetin alfa or epoetin alfa for CIA (Hgb < or = 10.0). Data collection
      variables included patient demographics, cancer diagnosis, chemotherapy
      treatment(s), laboratory data, erythropoeisis stimulation data, and transfusions.
      Sample size calculations were set to detect a 20% transfusion rate difference
      between the two groups. Chi-square, Fisher exact test and student t tests were
      used for statistical analysis. RESULTS: 123 patients were eligible for analysis
      (60 darbepoetin alfa; 62 epoetin alfa). 93% of darbepoetin alfa patients received
      200 mg every other week, while 86% of epoetin alfa patients received 40,000 U
      weekly. The darbepoetin alfa and epoetin alfa groups were similar in respect to
      age, race, tumor type, histology, previous chemotherapy, number of chemotherapy
      agents, weeks of erythropoietic stimulation, and baseline serum levels of
      creatinine and hemoglobin. The mean baseline Hgb and change in Hgb was similar
      for each group (darbepoetin alfa = 11.2, 2.5 and epoetin alfa = 11.3, 2.3).
      Twenty one (35%) of the darbepoetin alfa patients received a transfusion of
      packed red blood cells compared to 12 (19%) of epoetin alfa patients (p = 0.05).
      CONCLUSIONS: This retrospective analysis powered to detect differences in
      transfusion rates revealed a statistically significant difference in transfusion
      rates between darbepoetin alfa and epoetin alfa for the treatment of CIA. These
      data warrant a randomized prospective trial in gynecologic oncology patients with
      careful attention to the timing of initiation of treatment, dosing regimens, and
      titration of growth factor.

PMID- 16406065
TI  - Low-dose warfarin does not decrease the rate of thrombosis in patients with
      cervix and vulvo-vaginal cancer treated with chemotherapy, radiation, and
      erythropoeitin.
AB  - OBJECTIVES: We had previously reported an association between the use of
      recombinant human erythropoietin (rHuEPO) and thrombosis in patients with cervix
      and vulvo-vaginal cancer treated with chemotherapy and radiation. We hypothesized
      that low-dose warfarin would be effective prevention for thromboembolic events in
      this setting. METHODS: A retrospective analysis of patients with cervical or
      vulvo-vaginal carcinoma receiving chemoradiation and rHuEpo was performed. Thirty
      two patients received rHuEpo alone, and 24 received warfarin (1-2 mg) and rHuEpo.
      The primary endpoint was objectively proven symptomatic venous thrombosis.
      RESULTS: There was no difference in the baseline characteristics (e.g. age,
      stage, body mass index, mean and peak hemoglobin, WBC and platelet counts, and
      number of transfusions) between these two groups. The rate of thrombosis also was
      not statistically different (P = 0.62). Nine of 24 patients had a symptomatic
      deep vein thrombosis (DVT) while receiving warfarin compared to 10 of 32 patients
      not on warfarin. There was no difference between the two groups in the percentage
      of patients with upper extremity DVT (P = 0.83) or lower extremity DVT (P =
      0.64). CONCLUSION: Daily low-dose warfarin did not alter the incidence of
      symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received
      rHuEpo in conjunction with chemoradiation.

PMID- 16406066
TI  - Structure basis for antitumor effect of aplyronine a.
AB  - Aplyronine A, isolated from the sea hare Aplysia kurodai, possesses an
      exceedingly potent antitumor effect in vivo and it is one of the promising
      candidates as an anticancer drug. This macrolide is known to depolymerize F-actin
      and inhibit the polymerization of actin by forming a 1:1 complex with monomeric
      actin. The first complex structure of actin-aplyronine A was determined via a
      synchrotron X-ray analysis at a 1.45 A resolution. As expected, aplyronine A
      binds to a hydrophobic cleft composed of subdomains 1 and 3 of actin by
      intercalating its aliphatic tail part into the actin molecule as do the other
      reported F-actin depolymerizing agents. Unexpectedly, this complex structure
      shows the specific structural features around the trimethylserine moiety,
      revealed as an important moiety of aplyronine A for cytotoxicity against HeLa
      cells. Combining this result and our previous one, the moiety should strongly
      relate to the specific biological activity of aplyronine A; i.e. a potent
      antitumor effect.

PMID- 16406067
TI  - The incoherent feed-forward loop accelerates the response-time of the gal system
      of Escherichia coli.
AB  - Complex gene regulation networks are made of simple recurring gene circuits
      called network motifs. One of the most common network motifs is the incoherent
      type-1 feed-forward loop (I1-FFL), in which a transcription activator activates a
      gene directly, and also activates a repressor of the gene. Mathematical modeling
      suggested that the I1-FFL can show two dynamical features: a transient pulse of
      gene expression, and acceleration of the dynamics of the target gene. It is
      important to experimentally study the dynamics of this motif in living cells, to
      test whether it carries out these functions even when embedded within additional
      interactions in the cell. Here, we address this using a system with incoherent
      feed-forward loop connectivity, the galactose (gal) system of Escherichia coli.
      We measured the dynamics of this system in response to inducing signals at high
      temporal resolution and accuracy by means of green fluorescent protein reporters.
      We show that the galactose system displays accelerated turn-on dynamics. The
      acceleration is abolished in strains and conditions that disrupt the I1-FFL. The
      I1-FFL motif in the gal system works as theoretically predicted despite being
      embedded in several additional feedback loops. Response acceleration may be
      performed by the incoherent feed-forward loop modules that are found in diverse
      systems from bacteria to humans.

PMID- 16406068
TI  - Individual metal ligands play distinct functional roles in the zinc sensor
      Staphylococcus aureus CzrA.
AB  - Recent studies on metalloregulatory proteins suggest that coordination
      number/geometry and metal ion availability in a host cytosol are key determinants
      for biological specificity. Here, we investigate the contribution that individual
      metal ligands of the alpha5 sensing site of Staphylococcus aureus CzrA (Asp84,
      His86, His97', and His100') make to in vitro metal ion binding affinity,
      coordination geometry, and allosteric negative regulation of DNA
      operator/promoter region binding. All ligand substitution mutants exhibit
      significantly reduced metal ion binding affinity (K(Me)) by > or =10(3) M(-1).
      Substitutions of Asp84 and His97 give rise to non-native coordination geometries
      upon metal binding and are non-functional in allosteric coupling of metal and DNA
      binding (DeltaG(coupling) approximately 0 kcal mol(-1)). In contrast, His86 and
      His100 could be readily substituted with potentially liganding (Asp, Glu) and
      poorly liganding (Asn, Gln) residues with significant native-like tetrahedral
      metal coordination geometry retained in these mutants, leading to strong
      functional coupling (DeltaG(coupling) > or = +3.0 kcal mol(-1)). 1H-(15)N
      heteronuclear single quantum coherence (HSQC) spectra of wild-type and mutant
      CzrAs reveal that all H86 and H100 substitution mutants undergo 4 degrees
      structural switching on binding Zn(II), while D84N, H97N and H97D CzrAs do not.
      Thus, only those variant CzrAs that retain some tetrahedral coordination geometry
      characteristic of wild-type CzrA upon metal binding are capable of driving 4
      degrees structural conformational changes linked to allosteric regulation of DNA
      binding in vitro, irrespective of the magnitude of K(Me).

PMID- 16406069
TI  - Structural analyses of Sum1-1p-dependent transcriptionally silent chromatin in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, transcriptional silencing of the cryptic mating loci
      HML and HMR is established by the combined actions of cis-acting silencers and
      trans-acting proteins, including Sir2p, Sir3p and Sir4p. The Sir proteins serve
      as an integral part of a special silent chromatin at the HM loci. Deletion of any
      of the SIR2-SIR4 genes leads to a complete loss of silencing. However, the SUM1-1
      mutation can restore silencing at the HM loci. Recently, it has been shown that
      Sum1-1p is directed to the silencers and internal regions of the HM loci, and
      interacts with the Hst1p histone deacetylase that is a paralog of the Sir2p
      histone deacetylase. Like Sir-dependent silent chromatin, Sum1-1p-dependent
      chromatin is hypoacetylated. These suggest that Sum1-1p and Hst1p play roles
      similar to those of the Sir proteins in promoting transcriptional silencing.
      Here, we examine whether Sum1-1p-dependent chromatin is similar to Sir-dependent
      silent chromatin, which is characterized by densely and precisely positioned
      nucleosomes. We demonstrate that Sum1-1p-dependent primary chromatin structure at
      HMR largely resembles, but is not identical with, Sir-dependent silent chromatin,
      whereas Sum1-1p-dependent HML chromatin largely resembles, but is not identical
      with, derepressed chromatin found in a sir- background. This correlates with the
      previous finding that SUM1-1 restores silencing more efficiently at HMR than at
      HML. We show also that DNA in Sum1-1p-dependent silent chromatin assumes a
      distinct topology. Moreover, we present evidence indicating that Sum1-1p can
      increase the stability of Sir-dependent silent chromatin, thereby providing an
      explanation for the finding that SUM1-1 enhances HML/HMR silencing in a SIR+
      background.

PMID- 16406070
TI  - The solution structure of the native K50 Bicoid homeodomain bound to the
      consensus TAATCC DNA-binding site.
AB  - The solution structure of the homeodomain of the Drosophila morphogenic protein
      Bicoid (Bcd) complexed with a TAATCC DNA site is described. Bicoid is the only
      known protein that uses a homeodomain to regulate translation, as well as
      transcription, by binding to both RNA and DNA during early Drosophila
      development; in addition, the Bcd homeodomain can recognize an array of different
      DNA sites. The dual functionality and broad recognition capabilities signify that
      the Bcd homeodomain may possess unique structural/dynamic properties. Bicoid is
      the founding member of the K50 class of homeodomain proteins, containing a lysine
      residue at the critical 50th position (K50) of the homeodomain sequence, a
      residue required for DNA and RNA recognition; Bcd also has an arginine residue at
      the 54th position (R54), which is essential for RNA recognition. Bcd is the only
      known homeodomain with the K50/R54 combination of residues. The Bcd structure
      indicates that this homeodomain conforms to the conserved topology of the
      homeodomain motif, but exhibits a significant variation from other homeodomain
      structures at the end of helix 1. A key result is the observation that the side
      chains of the DNA-contacting residues K50, N51 and R54 all show strong signs of
      flexibility in the protein-DNA interface. This finding is supportive of the
      adaptive-recognition theory of protein-DNA interactions.

PMID- 16406071
TI  - Variable metallation of human superoxide dismutase: atomic resolution crystal
      structures of Cu-Zn, Zn-Zn and as-isolated wild-type enzymes.
AB  - Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of
      oxidative stress. Mutations in SOD1 are linked to the familial form of
      amyotrophic lateral sclerosis. Several hypotheses for their toxicity involve the
      mis-metallation of the enzyme. We present atomic-resolution crystal structures
      and biophysical data for human SOD1 in three metallation states: Zn-Zn, Cu-Zn and
      as-isolated. These data represent the first atomic-resolution structures for
      human SOD1, the first structure of a reduced SOD1, and the first structure of a
      fully Zn-substituted SOD1 enzyme. Recombinantly expressed as-isolated SOD1
      contains a mixture of Zn and Cu at the Cu-binding site. The Zn-Zn structure
      appears to be at least as stable as the correctly (Cu-Zn) metallated enzyme.
      These data raise the possibility that in a cellular environment with low
      availability of free copper, Zn-Zn may be the preferred metallation state of SOD1
      prior to its interaction with the copper chaperone.

PMID- 16406072
TI  - Tracheal atresia as part of an exceptional combination of malformations.
AB  - A case of a premature infant with tracheal atresia together with an exceptional
      combination of congenital abnormalities that partially corresponds to the TACRD
      and VACTERL associations is presented. Tracheal atresia was not detectable in the
      prenatal ultrasound due to lacking of the typical diaphragmatic and pulmonary
      findings because of the esophago-tracheal fistula, and therefore the
      resuscitation team was not prepared for this severe airway complication. After
      prolonged resuscitation efforts were terminated and the newborn expired after
      birth. Even without typical warning signs physicians have to be aware of tracheal
      atresia and airway obstruction if VACTERL or TACRD associations are diagnosed.

PMID- 16406073
TI  - Airway reconstruction in children with recurrent respiratory papillomatosis.
AB  - OBJECTIVE: To determine if children with recurrent respiratory papillomatosis
      were at increased risk of complications due to their disease following major
      airway reconstruction. METHODS: We retrospectively reviewed our airway surgery
      database and the medical records of all children diagnosed with recurrent
      respiratory papillomatosis who were evaluated at Cincinnati Children's Hospital
      Medical Center between January 1998 and August 2003. All patients with active
      airway papillomas or a history of recurrent respiratory papillomatosis who
      underwent open airway reconstruction at our institution were included in the
      study. RESULTS: Seven children with recurrent respiratory papillomatosis
      underwent major airway reconstruction. Six children had tracheotomies and five
      are now decannulated following their airway reconstruction. Five children had
      active papillomas at the time of surgery and none had significant worsening of
      their papillomas following their procedures. Two patients in remission underwent
      airway reconstruction without recurrence of their papillomas. CONCLUSIONS: Major
      airway reconstruction can be safely performed in children with recurrent
      respiratory papillomatosis.

PMID- 16406074
TI  - Recurrent fetal rhabdomyoma of the head and neck.
AB  - We present a case of a congenital fetal rhabdomyoma which recurred after surgical
      excision. A review of the patient's chart, imaging studies, operative reports and
      histologic findings were conducted. A congenital fetal rhabdomyoma involving the
      head and neck region diagnosed prenatally by ultrasound and MRI was surgically
      excised without complications. The patient presented with recurrence of the tumor
      fourteen months after the initial surgery. This case report is supplemented with
      a review of the relevant literature on congenital fetal rhabdomyoma. This is the
      fifth documented case of recurrence of a fetal rhabdomyoma. Extracardiac
      rhabdomyomas are extremely rare benign tumors. Complete excision of these lesions
      is curative with only a handful of recurrences documented in the literature.
      Close follow up and a complete workup to rule out rhabdomyosarcoma is warranted
      in all cases of recurrence.

PMID- 16406075
TI  - Alteration of adenoid tissue alkaline and acid phosphatase in children with
      secretory otitis media.
AB  - OBJECTIVE: The role of pharyngeal lymphoid tissue in etiopathogenesis of
      secretory otitis is not yet defined. The influence of tonsillar and adenoid mass,
      weight, obstruction of naspharyngeal orrifitium, bacterial reservoire or some
      immunological events are of scientific interest. Tissue nonspecific alkaline
      phosphatase (TNAP) and acid phosphatase (ACP) are enzymes detected in lymphoid
      tissue, TNAP as characteristic of B cells, ACP as a characteristic of macrophages
      and folucullardentritic cells. These enzymes interfere in cell metabolism by
      removing 5' phosphate group from nucleotides and proteins. Specific activity and
      kinetic properties were studied in palatinal tonsils and adenoids of children
      with secretory otitis (OME) and compared with children with recurrent tonsillitis
      without ear involvement. METHOD: Adenoid and tonsillar tissue of l7 children with
      OME and 30 children with recurrent tonsillitis were subjected to biochemical
      investigation using method of releasing of p-nitrophenol from p
      nitrophenylphosphate (pNPP). Kinetic parameters as Michaelis-Menten constant were
      calculated by non-linear regression estimation method. RESULTS: Specific activity
      of adenoid alkaline phosphatase was lower in children with OME in relation to
      children with recurrent tonsillitis (t=5.733507, p<0.01). Specific activity of
      adenoid acid phosphatase was also lower in children with OME (t=3.655456,
      p<0.01). pH optimum for both enzymes was the same in these two groups of
      children. Michaelis-Menten constant for both enzymes was significantly higher in
      adenoid of children with OME than in children with recurrent tonsillitis
      suggesting lower enzyme affinity for the substrate. CONCLUSION: Differences in
      specific activities and kinetic properties of adenoid alkaline and acid
      phosphatases between children with OME and children with recurrent tonsillitis
      without OME were verified in this study. The results of the study are not able to
      explain the alteration of alkaline and acid phosphatase characteristics but could
      point to some possible and specific role of nasopharyngeal lymphoid tissue in
      pathogenesis of secretary otitis.

PMID- 16406076
TI  - Contact diode laser myringotomy for medium-duration middle ear ventilation in
      children.
AB  - OBJECTIVE: To prospectively compare contact diode laser for myringotomy (CDLM) to
      myringotomy with tube insertion (M&T) for the surgical management of otitis media
      with effusion (OME) in children. STUDY DESIGN AND SETTING: Prospective randomized
      controlled study at a tertiary care pediatric institution. METHODS: Thirty
      children for whom PE tube insertion was indicated were randomized for treatment
      by CDLM or by M&T, in order to investigate length of time for middle ear
      ventilation, and complication rates. Surgical time was measured, post-operative
      parental questionnaires were reviewed, and follow-up examinations were performed.
      INTERVENTION: Middle ear ventilation by CDLM or M&T. RESULTS: Middle ear
      ventilation by CDLM took an average of 4.1min, and was maintained for an average
      of 3.5 months, compared to surgical time of 10.2min for M&T, and duration of
      middle ear ventilation of 6.3 months. These differences were statistically
      significant (p=0.005 for surgical time, and p<0.001 for duration of ventilation).
      Complication rates were equivalent. CONCLUSION: CDLM allowed for medium-duration
      middle ear ventilation in children compared to M&T. Further study to clarify the
      role of CDLM in the management of OME in children is indicated.

PMID- 16406077
TI  - Investigation of ototoxic effects of Taxol on a mice model.
AB  - OBJECTIVE: To investigate the effects of taxol on the inner ear in a mice model.
      METHODS: This study was performed on 112 ears of 56 albino Swiss mice. All
      animals underwent baseline auditory brainstem response (ABR) testing bilaterally
      and baseline Peak Equivalent Sound Pressure Levels (PESPLs) were obtained. The
      mice were randomly assigned to seven groups consisting of one control and six
      study groups. The control group received no medications while the mice in groups
      1-6 received 1 x 60, 1 x 20, 2 x 20, 3 x 20, 4 x 20 and 5 x 20 mg/kg taxol
      intraperitoneally. Control ABR assessments were performed 3 weeks after the last
      dose. The animals were then sacrificed while still anaesthetised and the bullae
      (cochleae included) were dissected from their temporal bones. Haematoxylin-eosin
      and Masson's trichrome stains were used to demonstrate connective tissue, and
      periodic acid Schiff (PAS) stain was used to highlight epithelial elements.
      RESULTS: Significant decreases in the hearing levels were observed in all the
      groups which received taxol. No correlation was observed between the dose given
      and the degree of hearing loss. The sections from the control group showed no
      histopathologic abnormalities while the sections from the study groups
      demonstrated vacuolisation in the epithelial cells of the spiral limbus, and the
      stria vascularis, vacuolisation of the fibroblasts and decreasing the number of
      the fibroblasts in the spiral limbus. CONCLUSION: Taxol causes mild to moderate
      sensorineural hearing loss in mice. Histopathologically, there were degenerative
      changes in the cochlea resembling the ones that take place in salisylate and
      interferon alpha 2a ototoxicity which are thought to be reversible. There was no
      sensory cell loss. The hearing loss begins with doses less than or equal to
      20mg/kg and is not dose dependent after this dose. Hearing monitorisation with
      audiologic evaluation is strongly recommended before and during the use of the
      drug in human subjects.

PMID- 16406078
TI  - Death following tonsillectomy in a child with Williams syndrome.
AB  - Williams syndrome (WS) is an uncommon genetic syndrome due to a deletion of
      several genes on chromosome 7. The syndrome is associated with dysmorphic facies,
      neurological manifestations, idiopathic hypercalcemia, and cardiac abnormalities,
      particularly supravalvular aortic stenosis (SVAS). Children with Williams
      syndrome may have chronic serous otitis media and/or obstructive sleep apnea.
      Hyperacusis is also commonly seen in these children. We report a case of sudden
      death at the time of tonsillectomy/adenoidectomy and bilateral tympanostomy tube
      placement in a child with Williams syndrome. All children with Williams syndrome
      should have a thorough cardiac evaluation before undergoing general anesthesia
      for any otolaryngologic procedure.

PMID- 16406080
TI  - Single stage near total resection of massive pediatric head and neck plexiform
      neurofibromas.
AB  - OBJECTIVE: Plexiform neurofibromas of the head and neck in neurofibromatosis type
      1 (NF 1) carry a significant morbidity with substantial loss of function as well
      as significant cosmetic problems. We describe our experience with early
      aggressive surgical intervention in such patients in order to avert these
      problems. METHODS: Retrospective review of four consecutive pediatric patients
      with massive head and neck plexiform neurofibromas who underwent single stage
      near total or sub-total tumor resections. RESULTS: All four patients were
      referred for obstructive airway symptoms. Each patient experienced complete
      relief of symptoms and return of function without additional neurological
      deficits. There were two minor complications and no major complications of
      surgical resection. There have been no recurrences to date, with follow-up
      ranging from 15 months to 5 years. CONCLUSIONS: Early surgical intervention of NF
      1 patients with plexiform neurofibromas of the head and neck with a goal of near
      total resection avoids the loss of function associated with these tumors, such as
      tracheostomy dependence, swallowing difficulty, and speech problems, and prevents
      the inexorable progression of substantial cosmetic deformity. Successful
      management of these complex lesions requires detailed preoperative planning,
      advanced surgical techniques, and vigilant postoperative care.

PMID- 16406079
TI  - Interleukin-18/-607 gene polymorphism in allergic rhinitis.
AB  - OBJECTIVES: Allergic rhinitis is a chronic inflammatory disease with a genetic
      background, and IL-18 (formerly IFN-gamma-inducing factor) is a well-known pro
      inflammatory cytokine. The aim of this study was to investigate whether the IL
      18/-607 promoter polymorphisms were associated with allergic rhinitis in the
      Korean population. STUDY DESIGN: Prospective study. METHODS: Deoxyribonucleic
      acid was obtained from the blood samples of 160 Korean children with allergic
      rhinitis and from 166 healthy controls. The IL-18/-607 polymorphism was analyzed
      by polymerase chain reaction and restriction fragment length polymorphism (PCR
      RFLP) analysis. RESULTS: The frequency of the AC genotype of the IL-18/-607 gene
      polymorphism was significantly greater in allergic rhinitis patients than in
      controls (P<0.05). CONCLUSIONS: The A allele in the IL-18/-607 gene promoter
      region may be involved in the development of allergic rhinitis in the Korean
      population.

PMID- 16406081
TI  - Oral lesions in Brazilian HIV-infected children undergoing HAART.
AB  - INTRODUCTION: The advent of new antiretroviral drugs such as protease inhibitors
      (PI) has generated sensible changes in oral manifestation patterns in human
      immunodeficiency virus (HIV) infected adult patients. OBJECTIVES: The purpose of
      the present study was to assess whether the use of highly active antiretroviral
      therapy (HAART) has brought changes to pattern and prevalence of oral lesions
      related to HIV in the HIV-infected pediatric population. CASUISTIC AND METHOD: We
      analyzed medical charts of 471 children aged zero to 12 years and 11 months with
      HIV infection and followed up by the Ambulatory of AIDS, Clinical
      Otorhinolaryngology, Hospital das Clinicas, Medical School, Sao Paulo University,
      from January 1990 to December 2004. Four hundred and fifty-nine children were
      divided into two groups, according to age range: X (0-5 years and 11 months) and
      Y (6-12 years and 11 months). These groups were subdivided into four subgroups,
      according to use of ART (antiretroviral therapy without PI) or HAART. We recorded
      data related to type of oral lesion presented, as well as serum CD4+ lymphocyte
      count. The groups were compared concerning prevalence and presentation pattern of
      oral manifestations. RESULTS: Out of 459 children, 144 (31.4%) had oral lesions.
      We observed that in children aged 6-12 years and 11 months who were taking HAART,
      there was lower prevalence of oral lesions (p=0.005), specially hairy leukoplakia
      (p<0.02), without any affection to the common presentation pattern of these
      lesions. The same subgroup also had higher serum CD4+ lymphocyte counts
      (p<0.001). CONCLUSION: We concluded that use of HAART could lead to reduction in
      prevalence of oral lesions in HIV-infected children.

PMID- 16406082
TI  - Deficiencies of cross-training between pediatrics and otolaryngology: a survey of
      specialists in Canada.
AB  - OBJECTIVE: Conditions relating to the ear, nose and throat are very frequent
      problems encountered by general pediatricians. Similarly, a major percentage of
      patients seen and operated on by the general otolaryngologist are of the
      pediatric age group. The pilot study demonstrated that pediatric program
      directors of both specialties in Canada have identified a deficiency of cross
      training and desire the need for more cross-training. The aim of this study was
      to survey practicing physicians of both specialties for their input. METHODS:
      Surveys were sent to a large cross-section of pediatricians and otolaryngologists
      in Canada. They were asked to complete a questionnaire relating to their training
      experience, their desired training, important topics and general comments.
      Demographic data were collected including generalist versus sub-specialist, the
      year that residency was completed and country of training. Results were tabulated
      and analyzed. RESULTS: The response rate was high, being 70.6% and 76.2% for
      pediatricians and otolaryngologists, respectively. One hundred percent of
      pediatricians indicated that formal training by otolaryngologists was necessary,
      while 95% of otolaryngologists indicate a need for formal training by
      pediatricians during residency. Pediatricians desire more training using all
      three educational venues, namely lectures, clinics and rotations. While they are
      receiving lectures more often, they indicate that clinics are the most important
      mode of education. Otolaryngologists desire more formal training by pediatricians
      in the areas of lectures and clinics. They indicate the most important mode of
      education is lectures. There was no significant difference between generalists
      and sub-specialists or based on country of training for either group. There is
      some indication, in both specialties, of an increase of cross-training occurring
      within the past five years. CONCLUSIONS: This study has shown that there is a
      perceived deficiency of cross-training between the two specialties. Both
      pediatricians and otolaryngologists have indicated that they need more formal
      cross-training. This is a very important area to address, as this study relates
      directly to the optimum health of children in Canada and worldwide.

PMID- 16406083
TI  - Sleep disordered breathing in children with achondroplasia. Part 2. Relationship
      with craniofacial and airway morphology.
AB  - We evaluated the craniofacial and airway morphology in children with
      achondroplasia complicated by snoring and apnea during sleep (AP group) in
      comparison with children with snoring and apnea during sleep without chromosomal
      aberrations (adenoid group) and healthy children without sleep disordered
      breathing or malalignment (healthy group). Lateral cephalograms in 10 children
      each (four males and six females) in the three groups were analyzed. When the AP
      and healthy groups were compared, the AP group showed significantly lower values
      for facial depth, nasal floor length, point A, point pog, and saddle angle
      (p<0.01) and significantly higher values for mandibular plane angle and gonial
      angle (p<0.01) regarding craniofacial morphology and significantly lower values
      for D-AD1, D-AD2, and upper pharynx (p<0.01) regarding airway morphology. When
      the AP and adenoid groups were compared, the AP group showed significantly lower
      values for facial depth, nasal floor length, point A, point pog, and saddle angle
      (p<0.01) and significantly higher values for mandibular plane angle and gonial
      angle (p<0.01) regarding craniofacial morphology and significantly lower values
      for D-AD1, D-AD2, and upper pharynx (p<0.05) regarding airway morphology. Thus,
      the craniofacial/airway morphology in the AP group was characterized by upper
      airway stenosis, a retruded position of the chin, and an increased mandibular
      plane angle due to partial early ossification of cranial bones, and an increased
      lower facial height due to an increased mandibular angle, which may tend to
      induce sleep snoring and apnea.

PMID- 16406084
TI  - Evaluation of the biomechanical behavior of maxillary central incisors restored
      by means of endocrowns compared to a natural tooth: a 3D static linear finite
      elements analysis.
AB  - OBJECTIVE: The present study aimed at evaluating different restoring
      configurations of a crownless maxillary central incisor, in order to compare the
      biomechanical behavior of the restored tooth with that of a sound tooth.
      MATERIALS AND METHODS: A 3D FE model of a maxillary central incisor is presented.
      An arbitrary static force of 10 N was applied with an angulation of 125 degrees
      to the tooth longitudinal axis at level of the palatal surface of the crown.
      Different material configurations were tested: composite, syntered alumina,
      feldspathic ceramic endocrowns and glass post resorations with syntered alumina
      and feldspathic ceramic crown. RESULTS: High modulus materials used for the
      restoration strongly alter the natural biomechanical behavior of the tooth.
      Critical areas of high stress concentration are the restoration-cement-dentin
      interface both in the root canal and on the buccal and lingual aspects of the
      tooth-restoration interface. Materials with mechanical properties underposable to
      that of dentin or enamel improve the biomechanical behavior of the restored tooth
      reducing the areas of high stress concentration. SIGNIFICANCE: The use of
      endocrown restorations present the advantage of reducing the interfaces of the
      restorative system. The choice of the restorative materials should be carefully
      evaluated. Materials with mechanical properties similar to those of sound teeth
      improve the reliability of the restoartive system.

PMID- 16406085
TI  - An NMDA receptor-dependent hydroxyl radical pathway in the rabbit hypothalamus
      may mediate lipopolysaccharide fever.
AB  - The aim of this study was to investigate the effects of antioxidants (e.g. alpha
      lipoic acid and N-acetyl-L-cysteine) as well as N-methyl-D-aspartate (NMDA)
      receptor antagonists (e.g. MK-801 and LY235959) on the changes of both core
      temperature and hypothalamic levels of 2,3-dihydroxybenzoic acid (2,3-DHBA)
      induced by systemic administration of lipopolysaccharide (LPS) in rabbits. The
      measurements of 2,3-DHBA were used as an index of the intrahypothalamic levels of
      hydroxyl radicals. Intravenous administration of LPS (2-10 microg/kg) elicited a
      biphasic febrile response, with the core temperature maxima at 80 and 200 min
      post-injection. Each core temperature rise was accompanied by a distinct wave of
      cellular concentrations of 2,3-DHBA in the hypothalamus. The rise in both the
      core temperature and hypothalamic 2,3-DHBA could be induced by direct injection
      of glutamate (100-400 microg in 10 microl/rabbit) into the cerebroventricular
      fluid system. Either the early or the late phase of fever rise and increased
      hypothalamic levels of 2,3-DHBA following systemic injection of LPS were
      significantly antagonized by pretreatment with injection of alpha-lipoic acid (5
      60 mg/kg, i.v.), N-acetyl-L-cysteine (2-20 mg/kg, i.v.), MK-801 (0.1-1 mg/kg,
      i.m.), or LY235959 (0.1-1 mg/kg, i.v.) 1 h before LPS injection. The increased
      levels of prostaglandin E(2) in the hypothalamus induced by LPS could be
      suppressed by alpha-lipoic acid or N-acetyl-L-cysteine pretreatment. These
      findings suggest that an NMDA receptor-dependent hydroxyl radical pathway in the
      hypothalamus of rabbit brain may mediate both the early and late phases of the
      fever induced by LPS.

PMID- 16406086
TI  - Recent developments in constitutive receptor activity and inverse agonism, and
      their potential for GPCR drug discovery.
AB  - The concept of constitutively active G-protein-coupled receptors is now firmly
      rooted in receptor pharmacology. Many independent research groups have
      contributed to its acceptance since its introduction by Costa and Herz in 1989.
      This concept necessitated a revised ligand classification, and a new category of
      inverse agonists was introduced alongside existing agonist and antagonist
      ligands. Initially, it was hoped that new therapeutic modalities would become
      available. However, the drug industry has not adopted inverse agonism as a design
      criterion and instead accepted that some compounds emerge as (neutral)
      antagonists in compound screening, whereas other compounds possess inverse
      agonistic activity. In this article, we summarize aspects of the impact of
      constitutive activity on the drug-discovery process: for example, its use in
      orphan receptor assays, its link with pharmacogenetics and genomics, and its
      relevance for currently marketed drugs.

PMID- 16406087
TI  - Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee.
AB  - Ca2+ is a universal intracellular messenger that controls a wide range of
      cellular processes. In pancreatic acinar cells, acetylcholine and cholecystokinin
      regulate secretion via generation of repetitive local cytosolic Ca2+ signals in
      the apical pole. Bile acids and non-oxidative alcohol metabolites can elicit
      abnormal cytosolic Ca2+ signals that are global and sustained and result in
      necrosis. Necrosis results from excessive loss of Ca2+ from the endoplasmic
      reticulum, which is mediated by Ca2+ release through specific channels and
      inhibition of Ca2+ pumps in intracellular stores, followed by entry of
      extracellular Ca2+. Reduction of the cellular ATP level has a major role in this
      process. These abnormal Ca2+ signals, which can be inhibited by caffeine, explain
      how excessive alcohol intake and biliary disease cause acute pancreatitis, an
      often-fatal human disease in which the pancreas digests itself and its
      surroundings.

PMID- 16406088
TI  - Glutamate receptors: variation in structure-function coupling.
AB  - Fast excitatory synaptic transmission in the CNS relies almost entirely on the
      neurotransmitter glutamate and its family of ion channel receptors. An
      appreciation of the coupling between agonist binding and channel opening has
      advanced rapidly during the past five years, largely as a result of new
      structural information about the agonist-binding site. Recent studies suggest
      that despite many structural similarities different family members use different
      mechanisms to translate agonist binding into channel opening.

PMID- 16406089
TI  - Is GAS1 a co-receptor for the GDNF family of ligands?
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) is a survival and maintenance
      factor for dopamine-containing neurons and motoneurons. GDNF belongs to a family
      of structurally related factors that includes neurturin (NRTN), artemin (ARTN)
      and persephin (PSPN). An initial step in the activation of signaling via the GDNF
      family of ligands (GFLs) is their binding to their cognate co-receptor GFR alpha.
      GAS1, an apparently unrelated protein, exhibits homology to GFR alpha and thus we
      hypothesize that GAS1 can serve as an alternative receptor for GFLs. The
      functional similarity between GFR alpha and GAS1 extends to their role in
      embryogenesis, differentiation and glia maintenance, and is substantiated by
      overlap in their expression profile, subcellular localization and structural
      details. We propose that the relative expression and localization of the two
      remote receptors, GFR alpha and GAS1, on the membranes of neuronal and glial
      cells determines whether these cells survive or undergo apoptotic death.

PMID- 16406091
TI  - Low molecular weight squash trypsin inhibitors from Sechium edule seeds.
AB  - Nine chromatographic components containing trypsin inhibitor activity were
      isolated from Sechium edule seeds by acetone fractionation, gel filtration,
      affinity chromatography and RP-HPLC in an overall yield of 46% of activity and
      0.05% of protein. The components obtained with highest yield of total activity
      and highest specific activity were sequenced by Edman degradation and their
      molecular masses determined by mass spectrometry. The inhibitors contained 31, 32
      and 27 residues per molecule and their sequences were: SETI-IIa,
      EDRKCPKILMRCKRDSDCLAKCTCQESGYCG; SETI-IIb, EEDRKCPKILMRCKRDSDCLAKCTCQESGYCG and
      SETI-V, CPRILMKCKLDTDCFPTCTCRPSGFCG. SETI-IIa and SETI-IIb, which differed by an
      amino-terminal E in the IIb form, were not separable under the conditions
      employed. The sequences are consistent with consensus sequences obtained from 37
      other inhibitors: CPriI1meCk_DSDCla_C_C_G_CG, where capital letters are invariant
      amino acid residues and lower case letters are the most preserved in this
      position. SETI-II and SETI-V form complexes with trypsin with a 1:1 stoichiometry
      and have dissociation constants of 5.4x10(-11)M and 1.1x10(-9)M, respectively.

PMID- 16406093
TI  - Microglial phenotype: is the commitment reversible?
AB  - Microglia, the standby cells for immune defense in the CNS, have a reputation for
      exacerbating the neural damage that occurs in neurodegenerative diseases.
      However, research over the past few years has established that microglia do not
      constitute a single, uniform cell population, but rather comprise a family of
      cells with diverse phenotypes--some that are beneficial and others that the CNS
      can barely tolerate and that are therefore destructive. This finding raised
      several questions. What instructs microglia to acquire a particular phenotype,
      and how do these phenotypes differ? How committed are microglia to a specific
      phenotype? Can destructive microglia become protective, and can protective
      microglia retain their beneficial phenotype even when they encounter a
      destructive environment? Here, we address these questions, and the background of
      research that elicited them.

PMID- 16406094
TI  - Complement regulator loss on apoptotic neuronal cells causes increased complement
      activation and promotes both phagocytosis and cell lysis.
AB  - In neuroinflammatory disease complement (C) activation and neuronal apoptosis
      occur in areas of active pathology. C has a role in clearing apoptotic debris,
      but is also known to cause necrotic cell death by insertion of the membrane
      attack complex (MAC). It is therefore unclear whether C is protective or
      injurious in this context. Here we examine C regulator expression and
      susceptibility to C activation, lysis and phagocytosis in human neuronal cells
      undergoing apoptosis in order to model the in vivo situation. We demonstrate that
      apoptotic neuronal lines lose the C regulators CD46 and CD59. Regulator loss
      occurred only on cells positive for apoptotic markers, and was caspase dependent.
      Both CD46 and CD59 were shed from cells, CD46 as a soluble form following MMP
      cleavage, and CD59 on apoptotic blebs and as a soluble form. Apoptotic cells
      activated C and were opsonised more readily than control cells; as a consequence
      they were more readily phagocytosed by macrophages than non-apoptotic cells.
      Susceptibility to C-mediated lysis was complicated in that early cells were more
      sensitive while late apoptotic cells were more resistant to killing. MMP
      inhibition protected against the increased lysis seen in early apoptotic cells,
      but had no effect on susceptibility of non-apoptotic cells to C-mediated lysis.
      Our studies suggest that C activation on apoptotic neuronal cells is delicately
      balanced between enhancing their safe disposal through phagocytosis, and
      triggering necrosis by C-mediated lysis. The data suggest that therapeutic MMP
      inhibition, by restricting loss of CD46, may limit neuronal damage in
      neurological disease.

PMID- 16406092
TI  - Orbitofrontal cortex, decision-making and drug addiction.
AB  - The orbitofrontal cortex, as a part of prefrontal cortex, is implicated in
      executive function. However, within this broad region, the orbitofrontal cortex
      is distinguished by its unique pattern of connections with crucial subcortical
      associative learning nodes, such as basolateral amygdala and nucleus accumbens.
      By virtue of these connections, the orbitofrontal cortex is uniquely positioned
      to use associative information to project into the future, and to use the value
      of perceived or expected outcomes to guide decisions. This review will discuss
      recent evidence that supports this proposal and will examine evidence that loss
      of this signal, as the result of drug-induced changes in these brain circuits,
      might account for the maladaptive decision-making that characterizes drug
      addiction.

PMID- 16406095
TI  - Modulation of expression and function of Toll-like receptor 3 in A549 and H292
      cells by histamine.
AB  - It was reported recently that histamine induced Toll-like receptor (TLR)2 and
      TLR4 expression in endothelial cells and enhanced their sensitivity to Gram
      positive and Gram-negative bacteria; and that TLRs were expressed in airway
      epithelial cells and that several inflammatory mediators modulated their
      expression. However, little is known of potential influence of histamine on TLRs
      in pulmonary epithelial cells. In the present study, effects of histamine on
      expression of TLRs in both human A549 and NCI-H292 cell lines were examined by
      using real-time quantitative RT-PCR analysis, flow cytometry and
      immunofluorescent staining. The results revealed that both cell types
      constitutively expressed mRNAs for TLR1-TLR10. Histamine up-regulated the
      expression of TLR3 mRNA by 12.3- and 11.6-fold, respectively in both cell types.
      The time course showed that histamine induced TLR3 mRNA expression was initiated
      at 30 min, nearly reached peak levels after 2 h and was sustained at least until
      12 h. Histamine also induced TLR3 protein expression in A549 and NCI-H292 cells.
      Histamine and poly (I:C), a specific TLR3 ligand stimulated interleukin (IL)-8
      secretion from both cell types. Moreover, histamine enhanced poly (I:C)-induced
      IL-8 secretion and phosphorylation of NF-kappaB in the two cell types, and
      histamine H1 receptor antagonists inhibited the action of histamine. In
      conclusion, histamine selectively up-regulated expression of TLR3, and stimulated
      IL-8 secretion from the cells. Histamine also enhanced poly (I:C) induced IL-8
      secretion and phosphorylation of NF-kappaB. These observations suggest that
      histamine might play an important role in enhancing the innate immune responses
      of airway to viral infection.

PMID- 16406096
TI  - Evaluation of the Pastorex meningitis kit for the rapid identification of
      Neisseria meningitidis serogroups A and W135.
AB  - The recent emergence of Neisseria meningitidis W135 as a cause of epidemic
      bacterial meningitis and the availability of a trivalent ACW135 vaccine have
      created a need for accurate and timely meningococcal serogroup determination for
      organization of epidemic vaccine response. The sensitivity and specificity of the
      Pastorex meningitis kit (Bio-Rad) to identify serogroups A and W135 in the
      African meningitis belt was assessed using PCR testing as the gold standard. The
      sensitivity and specificity for serogroups A and W135 were 87 and 85%,
      respectively, while the specificities were 93 and 97%. The positive and negative
      likelihood ratios for A were 12 and 0.14 and for W135 were 33 and 0.16. The
      positive and negative predictive values, computed to simulate an epidemic of
      meningococcal meningitis with an estimated 70% prevalence of N. meningitidis
      among suspected cases, were 97% and 75% for A and 99% and 73% for W135. In remote
      locations of the African meningitis belt, latex agglutination is the only
      currently available test that can rapidly determine meningococcal serogroup. This
      study showed that latex agglutination performs well and could be used during the
      epidemic season to determine appropriate vaccine response.

PMID- 16406097
TI  - Helminth infections in British troops following an operation in Sierra Leone.
AB  - One hundred and fifty-three British soldiers and 86 Royal Air Force (RAF)
      personnel were deployed on a hostage rescue operation in Sierra Leone. For 3 days
      they were exposed to various infection risks and 6 weeks later some of the
      soldiers presented with gastrointestinal complaints. Both groups were screened
      with structured questionnaires, blood investigations and (where indicated) faecal
      microscopy and charcoal culture for helminths. Definite and probable cases of
      helminth infection were treated with albendazole and all soldiers were screened
      again after 3 months. Among the soldiers investigated, 73/145 (50%) reported
      gastrointestinal symptoms and 70/139 (50%) had eosinophilia. Among these, 17/66
      (26%) had hookworm infection, 6/66 (9%) had Strongyloides stercoralis infection
      and 1/66 (2%) had Giardia lamblia infection. Eosinophilia was most strongly
      associated with entering the enemy camp and being in the platoon that attacked
      the area around the camp latrines. Among RAF personnel, who were not involved in
      activities on the ground, 3/86 (3%) had borderline eosinophilia. Treatment of
      105/153 (69%) soldiers with albendazole was well tolerated and, on follow-up
      screening 3 months later, 23/124 soldiers (19%) had gastrointestinal symptoms and
      18/121 (15%) had eosinophilia. Faecal investigations and schistosomiasis serology
      tests were all negative at this stage.

PMID- 16406098
TI  - Pathogenicity and immunogenicity in mice of vaccinia viruses mutated in the viral
      envelope proteins A33R and B5R.
AB  - The pathogenicity and immunogenicity in mice of WR.cl and WR.c3, two mutants of
      the Western Reserve (WR) strain of vaccinia virus, mutated in the A33R and B5R
      proteins of the outer envelope of the virus, respectively, were studied. WR.c1
      was the most attenuated virus, WR.c3 was somewhat more pathogenic, while WR was
      the most virulent of the three. While the WR and the WR.c3 viruses, intranasally
      inoculated into mice, spread efficiently to the different internal organs of the
      animal, including the brain, WR.c1 was restricted to the lungs only. Mice,
      intranasally infected with 500 plaque forming units of the WR, WR.c1, or WR.c3
      viruses, were protected against infection with a lethal dose of the WR strain.

PMID- 16406099
TI  - Ternary Cu(II) complexes, Cu(H(-1)L)(ACys-) and Cu(H(-2)L)(ACys-); L = peptides,
      ACys- = N-acetyl-cysteinate. Analogous complexes to the intermediates in the
      transport of Cu(II) from Cu(H(-2)L) to cysteine.
AB  - The Cu(II) in Cu(H(-2)L) has been postulated to be successively transported to
      cysteine (Cys) as follows; Cu(H(-2)L) <==> Cu(H(-2)L)(Cys*-) <==> Cu(H(-1)L)(Cys*
      ) --> Cu(H(-1)L)(Cys-), where Cys*- denotes the monodentate Cys-. N-acetyl
      cysteinate (ACys-) complexes Cu(H(-2)L)(ACys-) and Cu(H(-1)L)(ACys-), having
      similar coordination modes to Cu(H(-2)L)(Cys*-) and Cu(H(-1)L)(Cys*-),
      respectively, exhibited the S --> Cu(II) charge transfer absorption at 325-355 nm
      and the d-d absorption at 530-610 nm. A linear interrelation existed between the
      energies of the CD and d-d absorptions. Cu(H(-2)L)(ACys-) were in rapid
      equilibrium with Cu(H(-1)L)(ACys-). Upon forming the ternary complex, pK(c2) of
      the parent Cu(H(-1)L) was raised to more than 1.0. The formation constants (K) of
      the Cu(H(-1)L)(ACys-) species from Cu(H(-1)L) were bigger than those of Cu(H(
      2)L)(ACys-) from Cu(H(-2)L). The linear free-energy relationship existed between
      the free-energy change (deltaG) and the entropy change (deltaS) for the ternary
      complex formation. The rate constants (k1+) for the Cu(H(-1)L)(Cys-) formation
      closely correlated with the K values for Cu(H(-2)L)(ACys-). The ternary complexes
      containing ACys are considered to be analogous complexes to the intermediates in
      the transport of Cu(II) from peptides to cysteine.

PMID- 16406100
TI  - Study of transportation and distribution of PCBs using an ecologically simulated
      growth chamber.
AB  - This study was designed to investigate the transportation, distribution, and
      bioaccumulation of PCBs in various environmental media and compartments using an
      ecologically simulated growth chamber. Spatial and temporal trends of PCBs in the
      growth chamber were discussed. The release of PCB congeners in soil was affected
      by the amount of rainfall with the transporting direction moving away from PCBs
      contaminated point. Two pathways of PCBs accumulation in plants were the uptake
      of roots and the deposition on shoots/leaves. There were 29 PCB congeners been
      found in the lalang grass. Higher concentrations of lower chlorinated PCBs were
      identified than higher chlorinated PCBs because of relatively higher vapor
      pressure for lower chlorinated congeners. After 10months of monitoring, PCBs were
      detected in water samples which were contributed by the release of PCBs from
      leached soil. Analysis of sediment showed that the percentages of low- and mid
      chlorinated biphenyls were decreased 1% and 13%, respectively compared to the
      increase (14%) of high-chlorinated biphenyls. The increase of high-chlorinated
      PCBs was possibly caused by their low hydrophilicity which had resulted higher
      adsorption rate in sediment. All of five species of fish had been found
      significant amount of PCBs accumulation ( summation operatorPCBs: 21.7-102.1
      microg/g-lipid). The concentrations of PCBs in fish were varied significantly
      among species. The range of bioaccumulation factors (BAFs) among different
      species of fish could be as much as 5 times depending on the consumption habits
      of fish. The mass balance of PCBs distribution in the growth chamber was also
      discussed.

PMID- 16406101
TI  - Quantitative structure-activity relationship for prediction of the toxicity of
      polybrominated diphenyl ether (PBDE) congeners.
AB  - Levels of Polybrominated diphenyl ether (PBDEs) are increasing in the environment
      due to their use as flame retardants. The similarities of structure to
      polychlorinated biphenyl (PCB) congeners suggest that they may share similar
      toxicological properties, such as hepatic enzyme induction. In this work,
      quantitative structure-activity relationship (QSAR) models were constructed based
      on 406 descriptors for the logarithm of toxicology index (aryl hydrocarbon
      receptor relative binding affinities, AhR, I) of 18 PBDE congeners. The method
      used for building model is the Heuristic method, which is included in
      comprehensive descriptors for structural and statistical analysis (CODESSA)
      software. The best regression model involved four descriptors, which were related
      to the conformational changes, atomic reactivity, molecular electrostatic field,
      and non-uniformity of mass distribution in a molecule of PBDEs, etc. The high
      square of the correlation coefficient R(2)(0.903) showed the model was
      satisfactory.

PMID- 16406102
TI  - Effects of pallidotomy on motor symptoms in an animal model of Parkinson's
      disease.
AB  - The present study was designed to evaluate the motor effects of lesioning the
      internal globus pallidus in an animal model of Parkinson's disease. Fourty rats
      were divided into four groups (each of 10 rats) which received either unilateral
      6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle (mfb) plus sham
      surgery to the pallidum, sham surgery of mfb plus N-methyl-D-aspartate (NMDA)
      induced pallidal lesions, combined 6-OHDA mfb + NMDA pallidal lesions or sham
      surgery to both structures. Animals with 6-OHDA lesions developed significant
      ipsilateral biases in head position, body axis and circling after amphetamine
      challenge (all P < 0.05). Prominent contralateral deficits were present in
      sensorimotor response latency and contralateral circling was induced by
      apomorphine challenge (both P < 0.05). The addition of an NMDA pallidal lesion,
      improved the head position and body axis biases, as well as dopamine-agonist
      induced rotation and contralateral reaction time in a sensorimotor task (all P <
      0.05). There was, however, a slight worsening of sensorimotor response on the
      ipsilateral side (P < 0.05). Pallidal lesions in the absence of 6-OHDA lesions
      produced contralateral head position and body axis biases (both P < 0.05). These
      data indicate that pallidotomy improves some, but not all aspects of parkinsonian
      motor dysfunction in an animal model of Parkinson's disease (PD).

PMID- 16406103
TI  - Isolation rearing of mice induces deficits in prepulse inhibition of the startle
      response.
AB  - Male 129T2 and C57BL/6J mice were housed either in groups of three (socials) or
      singly (isolates) at weaning. Six and seven weeks later, prepulse inhibition
      (PPI), startle reactivity, and locomotor activity (LMA) were measured. Isolation
      reared mice of both strains exhibited PPI deficits compared to socially reared
      controls in at least one of the two PPI test sessions. Isolation rearing had no
      effect on startle reactivity or habituation and only 129T2 isolates exhibited
      increased LMA. Isolation rearing induced locomotor hyperactivity and PPI deficits
      in mice and may be an effective developmental manipulation to use in combination
      with studies of genetically altered mice.

PMID- 16406105
TI  - Reactions to threat and personality: psychometric differentiation of intensity
      and direction dimensions of human defensive behaviour.
AB  - Gray and McNaughton [Gray JA, McNaughton N. The neuropsychology of anxiety.
      Oxford: Oxford University Press; 2000] predict that fear is associated with
      orientation away from threat whereas anxiety is associated with orientation
      towards threat; this first dimension of 'defensive direction' is independent of a
      second dimension of 'defensive intensity'. Defensive reactions were measured
      using a threat scenario questionnaire developed by Blanchard et al. [Blanchard
      DC, Hynd AL, Minke KA, Minemoto T, Blanchard RJ. Human defensive behaviours to
      threat scenarios show parallels to fear- and anxiety-related defence patterns of
      non-human mammals. Neurosci Biobehav Rev 2001;25:761-70] who found that responses
      paralleled the defensive reactions of rodents faced with real threats. In a
      sample of 141 participants we replicated Blanchard et al.'s findings as well as
      confirming the Gray and McNaughton hypotheses. As predicted, trait anxiety was
      associated with a tendency to orientate towards threat. In addition, the
      personality trait of psychoticism (tough-mindedness) was related to defensive
      intensity with low scorers on psychoticism being more sensitive to threat in
      general and high scorers being more threat insensitive. A well-established
      personality measure of general punishment sensitivity, namely the Carver and
      White [Carver CS, White TL. Behavioural inhibition, behavioural activation, and
      affective responses to impending reward and punishment: the BIS/BAS scales. J
      Pers Soc Psychol 1994;67:319-33] BIS scale, was positively correlated with both
      defensive intensity and direction. These data indicate that the threat scenario
      questionnaire has some validity as a measure of human reactions to threat.

PMID- 16406104
TI  - Scopolamine and MK801-induced working memory deficits in rats are not reversed by
      CBD-rich cannabis extracts.
AB  - Smoking marijuana causes working and short-term memory deficits, an effect that
      is mediated by cannabinoid receptor (CB1) activation in the brain. While this may
      be due to the main psychoactive constituent Delta9-tetrahydrocannabinol (Delta9
      THC), plant extracts also contain other cannabinoid and terpenoid compounds with
      unknown properties. Towards this end, we have recently shown that high
      concentrations of plant extracts rich in cannabidiol (CBD) can reverse working
      memory deficits induced by Delta9-THC which is a remaining contaminant of this
      extract [Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential
      effects of THC- and CBD-rich cannabis-extracts on working memory in rats.
      Neuropahrmacology 2004;47:1170-9]. Since this effect was dose-dependent and
      indicative of memory enhancing qualities of the CBD-rich extract, this prompted a
      wider investigation into the effects of CBD on other forms of amnesia in order to
      determine the mechanism of action and to reveal its potency against
      anticholinergic and antiglutamatergic agents. We employed a spatial delayed
      matching to position task in the open-field water maze. Both scopolamine (0.2
      mg/kg i.p.) and dizocilpine (MK801: 0.1mg/kg i.p.) impaired working memory at
      delays of 30 s and 4 h. Two doses of CBD-rich extracts (5 and 10 mg/kg), which
      did not affect working memory when given alone, were unable to reverse these
      deficits when co-administered with scopolamine or MK801. These data suggest that
      reversal of working memory deficits by CBD-rich extracts are specific to the
      cannabinoid system and do not compensate for acutely induced cholinergic or
      glutamatergic receptor hypoactivity.

PMID- 16406106
TI  - Influence of differential housing on emotional behaviour and neurotrophin levels
      in mice.
AB  - Environmental enrichment condition (EC) induces profound behavioural,
      neurochemical and neuroanatomical changes. Increasing evidence has shown that the
      hippocampus, which is implicated in a range of cognitive functions, including
      learning and memory, is one of the most susceptible brain areas to the effects of
      enriched rearing. Recent work also suggests that the hippocampus is functionally
      segregated; lesion studies have shown that the dorsal hippocampus is important
      for spatial learning, whereas the ventral part is critical in emotional behaviour
      in rats. We investigated the effects of differential housing environments on
      anxiety-related behaviour and neurotrophin levels in dorsal and ventral
      hippocampus, and other brain regions. Ninety-six male and female C57BL/6 mice
      were reared in EC or standard housing condition (SC) for 4 months after weaning.
      Thereafter sixty-four animals were tested in the elevated plus-maze, open-field,
      novel-objects exploration and food neophobia. Thirty-two animals remained as
      untested. Subsequently, brain nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) were analysed in selected brain regions of the tested
      and non-tested animals. Differential housing influenced anxiety-related behaviour
      in the plus-maze and brain neurotrophins. Baseline levels of BDNF and NGF protein
      were differently distributed in dorsal and ventral parts of hippocampus in both
      male and female mice, with levels in the dorsal hippocampal being consistently
      higher than those in ventral hippocampus. Exposure to behavioural testing induced
      complex changes on neurotrophin levels in selected brain regions. This study
      demonstrates for the first time the differential distribution of normal levels of
      neurotrophin protein in dorsal and ventral hippocampus in mice, and these levels
      can be affected by environmental enrichment and have an impact on emotional
      behaviour.

PMID- 16406107
TI  - Effects of paraformaldehyde fixation on nicotinic acetylcholine receptor binding
      in adult and developing rat brain sections.
AB  - In vitro receptor autoradiography requires unfixed tissue sections, but
      incubation and washing procedures often result in substantial tissue damage in
      sections from developing brain, hindering quantitative and qualitative analysis.
      Formaldehyde fixation greatly preserves morphology. However, fixation can
      interfere with pharmacological properties of receptors, increase in non-specific
      background labeling, or even destroy ligand binding sites. Two mild fixation
      protocols, 0.2% paraformaldehyde (pFA) and pFA vapor fixation, were compared for
      their ability to improve tissue morphology in postnatal day 7 (P7) brain slices
      and maintain binding of [125I]-epibatidine and [125I]-alpha-bungarotoxin to
      heteromeric and homomeric nicotinic acetylcholine receptors, respectively.
      Fixation greatly improved the ability of P7 brain slices to withstand incubation
      and washing procedures during binding, resulting in minimal or no loss of tissue
      after prior 0.2% pFA or vapor fixation, respectively. In adults, distribution
      pattern of [125I]-epibatidine was identical in fixed and unfixed slices, with no
      difference in total and non-specific labeling. Distribution of [125I]-alphaBTX
      labeling was similarly unaffected by 0.2% pFA fixation, but vapor fixation
      increased total and non-specific binding signal. Thus, mild fixations greatly
      improve tissue quality during receptor binding procedures and can preserve
      pharmacological properties of nicotinic acetylcholine receptors. However,
      different receptors or ligands might exhibit differential sensitivity to fixation
      protocols.

PMID- 16406108
TI  - Microwear and morphology: functional relationships between human dental microwear
      and the mandible.
AB  - Microscopic pits and scratches form on teeth during chewing, but the extent to
      which their formation is influenced by mandibular morphology is unknown.
      Digitized micrographs of the base of facet nine of the first, second, and third
      mandibular molar were used to record microwear features from an archaeological
      sample of modern humans recovered from Semna South in northern Sudan (n=38; 100
      BC to AD 350). Microwear patterns of the molar row are correlated with mandibular
      corpus width and depth, and with mandibular length. Variations in shear and
      compression at the base of facet nine during chewing were inferred. It may be
      that some correlations between microwear and mandibular morphology are
      predictable, reflecting similar aspects of masticatory loading, though the full
      extent of the relationship remains to be resolved.

PMID- 16406109
TI  - Influence of long-term exposure to dietary cadmium on growth, maturation and
      reproduction of goldfish (subspecies: Prussian carp Carassius auratus gibelio
      B.).
AB  - The influence of long-term exposure of goldfish to dietary cadmium (Cd) on its
      accumulation in tissues, growth, ovarian development, luteinizing hormone (LH)
      secretion and a response to hormonal stimulation of spawning were evaluated. The
      study was conducted on four groups of females for the period of 3 years, from the
      age of 10 weeks to second spawning. Four doses of Cd were applied in the feed: 0
      (control group), 0.1, 1 and 10 mg Cd g(-1) of feed (wet weight). The highest dose
      of Cd (10 mg g(-1)) inhibited growth and caused several behavioural effects. In
      contrast, lower dose of Cd (1 mg g(-1)) stimulated fish growth. The doses of Cd
      from 0.1 to 1 mg Cd g(-1) did not influence ovarian development. The gonado
      somatic index (GSI) and histological analysis of ovaries showed no differences in
      ovarian development between the control group and the groups receiving these
      doses of Cd. However, in the group receiving the highest Cd dose, GSI decreased.
      This was associated with persistent, long-lasting elevation of plasma LH levels.
      Ovulation did not occur in this group. Injections of salmon GnRH-analogue
      (sGnRHa) alone or with domperidone (a dopamine receptor antagonist) in sexually
      mature fish caused an increase of LH levels in all groups, although in the group
      fed with the highest Cd dose the effect was weaker than in the other groups.
      After the first spawning season, a negative effect of lower Cd doses (0.1 and 1mg
      Cd g(-1)) on ovarian recrudescence (rebuilding of ovaries) and on the response to
      the consecutive hormonal stimulation of spawning was observed (lower number of
      ovulating females). There was a significantly higher content of Cd in the livers
      of fish than in their muscles. The results of hormonal stimulation of spawning
      and histological analysis of ovaries suggest that in goldfish cadmium acts mainly
      at the level of ovary rather than on the pituitary gland. We suppose that in the
      natural environment cadmium present in the feed can play an important role in the
      accumulation of this element in fish tissues and can influence vital
      physiological processes.

PMID- 16406110
TI  - Air pollution and lung cancer risks in China--a meta-analysis.
AB  - Lung cancer is a serious health problem in China, as in the rest of the world.
      Many studies have already proved that air pollution as well as other
      environmental factors can increase the risk of lung cancer. Based on
      epidemiological studies carried out in China, this paper proposes odds ratios
      (OR) to evaluate the risk of lung cancer from indoor air pollution for the
      Chinese population by applying the method of meta-analysis. For domestic coal use
      for heating and cooking, the pooled OR values are 1.83 (95% CI: 0.62-5.41) and
      2.66 (1.39-5.07) for women and both sexes, respectively. For indoor exposure to
      coal dust, the OR values are 2.52 (95% CI: 1.94-3.28) and 2.42 (1.62-3.63) for
      women and both sexes, respectively. Cooking oil vapor is another factor
      increasing lung cancer risk. The OR values are 2.12 (95%CI: 1.81-2.47), 1.78
      (1.50-2.12) and 6.20 (2.88-13.32) for nonsmoking women, women, and both sexes,
      respectively. Regarding environmental tobacco smoke, the pooled OR values are
      1.70 (95% CI: 1.32-2.18) and 1.64 (1.29-2.07) for nonsmoking women and both
      sexes, respectively. Funnel plots with statistical test have been applied to
      examine the publication bias, and the results implied that the analysis of coal
      consumption and cooking oil pollution might be affected by publication bias. The
      meta-analysis results confirm the association between lung cancer and indoor air
      pollution for the Chinese population.

PMID- 16406111
TI  - Cellular and molecular actions of dinitroaniline and phosphorothioamidate
      herbicides on Plasmodium falciparum: tubulin as a specific antimalarial target.
AB  - Microtubules play important roles in cell division, motility and structural
      integrity of malarial parasites. Some microtubule inhibitors disrupt parasite
      development at very low concentrations, but most of them also kill mammalian
      cells. However, the dinitroaniline family of herbicides, which bind specifically
      to plant tubulin, have inhibitory activity on plant cells but are relatively non
      toxic to human cells. Certain dinitroanilines are also inhibitory to various
      protozoal parasites including Plasmodium. Here we demonstrate that the
      dinitroanilines trifluralin and oryzalin inhibited progression of erythrocytic
      Plasmodium falciparum through schizogony, blocked mitotic division, and caused
      accumulation of abnormal microtubular structures. Moreover, radiolabelled
      trifluralin interacted with purified, recombinant parasite tubulins but to a much
      lesser extent with bovine tubulins. The phosphorothioamidate herbicide amiprophos
      methyl, which has the same herbicidal mechanism as dinitroanilines, also had
      antimalarial activity and a similar action on schizogony. These data suggest that
      P. falciparum tubulin contains a dinitroaniline/phosphorothioamidate-binding site
      that is not conserved in humans and might be a target for new antimalarial drugs.

PMID- 16406112
TI  - Long-term outcome of women who undergo panniculectomy at the time of gynecologic
      surgery.
AB  - OBJECTIVE: While panniculectomy has been shown to be a useful technique in obese
      women undergoing gynecologic surgery, the long-term outcome of these patients has
      been poorly described. The goal of this study was to determine the long-term
      outcomes and patient satisfaction of women who underwent panniculectomy at the
      time of pelvic surgery. METHODS: A retrospective review of patients who underwent
      panniculectomy at the time of pelvic surgery between 1996 and 2004 was performed.
      Postoperative complications and long-term trends in weight were evaluated.
      Patient satisfaction was assessed by telephone survey. RESULTS: Forty-two
      patients were identified. The mean EBL was 522 ml, the mean operating time was
      just over 4 h. Wound complications were noted in 36% of the subjects. Two weeks
      after the procedure, 86% of the women had a weight that was lower than their
      preoperative weight. Weight loss peaked 3 months postoperatively, 97% of the
      subjects had a net lower weight, with a mean loss of nearly 20 lb. Over the
      ensuing 2 years, weight loss gradually declined. After 2 years of follow-up, 62%
      of the women were below their preoperative body weights. The mean weight loss at
      24 months was 7 lb. Overall patient satisfaction with the procedure was high.
      Eighty-six percent of the subjects responded that they would undergo the
      procedure again given their outcome. CONCLUSIONS: Panniculectomy is well
      tolerated and associated with a high rate of patient satisfaction. Panniculectomy
      is a valuable component of gynecologic surgery in morbidly obese women.

PMID- 16406113
TI  - p14ARF and p16INK4A, two products of the same gene, are differently expressed in
      cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To study the expression patterns of two different tumor suppressor
      proteins p16INK4A and p14ARF in cervical lesions. Both proteins are encoded by
      the same INK4A/ARF gene on chromosome 9p21. The expression patterns of these two
      proteins, both playing a central role in the cell cycle, were analyzed in detail
      in CIN, carcinomas, and normal epithelium to test the hypothesis that p16INK4A
      positive cells also demonstrate p14ARF expression. METHODS: Serial tissue
      sections of 9 CIN1 lesions, 10 CIN2 lesions, 12 CIN3 lesions, and 7 carcinomas
      were stained with monoclonal antibodies against p16INK4A and p14ARF. The short
      fragment polymerase chain reaction hybridization line probe assay was used to
      detect HPV. RESULTS: Normal epithelium was negative for both proteins. Marked
      immunoreactivity (++) for p16INK4A and p14ARF was observed in 5/7 carcinomas,
      10/12 CIN3, and 1/10 CIN2 lesions and 0/9 CIN1 lesions. Simultaneous expression
      (+ or ++) was found in 19/22 CIN2/3 and not in CIN1 lesions. The fraction of
      p16INK4A-stained cells increased with CIN-grade. Overexpression of p14ARF was
      observed in a subpopulation of p16INK4A positive cells, and exclusively found in
      lesions infected with high-risk HPV. In two CIN3 lesions with early stromal
      invasion, p14ARF positivity was mainly found in the invasive cells. In
      carcinomas, all cells showed p16INK4A expression, whereas p14ARF was limited to
      the peripheral cells of the invasive tumor nests and individual migrating tumor
      cells. CONCLUSIONS: Overexpression of p14ARF is limited to a fraction of the
      p16INK4A-expressing cells and therefore it is likely that p14ARF- and p16INK4A
      expression are not induced by the same mechanisms. Before expression of p14ARF
      can be linked to invasion or invasive phenotype, larger series of (micro-)
      invasive squamous lesions need to be studied.

PMID- 16406114
TI  - Functional partitioning of epithelial protein kinase CaMKII in signal
      transduction.
AB  - The examination of the physiological role of CaMKII has made substantial progress
      in non-epithelial systems but little is known about its function in secretory
      epithelial cells. A prototypic exocrine cell, the acid secreting gastric parietal
      cell, largely redistributes its cytoplasmic tubulocisternal membranes (TC) to the
      secretory apical membrane (SA) after stimulation. We here present a dependence of
      physiological response on partitioned initial CaMKII activities redistributed
      between TC and SA. Initial acid secretion after cholinergic stimulation has
      doubled if activities of phosphatases PP1/PP2A and protein kinase PKC-alpha were
      inhibited by the inhibitors calyculin A and Go 6976. CaMKII appears to be
      integrated in multienzyme complexes each specific for TC and SA. Therein,
      PP1/PP2A and PKC-alpha were found to permanently counteract initial CaMKII
      activities in different modes of transregulation. Remarkably, a dys
      transregulated, hyperactive CaMKII at TC did not result in an increased acid
      secretion to the same extent. A simple mathematical model to estimate the share
      of TC- and SA-associated CaMKII activities in cholinergically induced acid
      secretion suggests that TC-associated CaMKII appears to autoregulate its
      contribution to the physiological response by a negative feedback control.
      Subcellular distribution and stimulus-dependent redistribution of domain
      associated CaMKII signalosomes indicate a fine balanced, adaptive system to
      guarantee a stable physiological response.

PMID- 16406115
TI  - Monocyte activation, but not granulocyte activation, is inhibited in the presence
      of developing ovarian follicles.
AB  - This study was set up to evaluate the influence of ovarian factors on the acute
      phase of the endotoxin-induced glomerular inflammatory reaction. Six groups of
      rats with permanent jugular vein cannulas were used. This included three groups
      with increased progesterone and/or 17beta-oestradiol concentrations (day 14
      pregnant rats, pseudopregnant rats and lactating rats), one group with the
      presence of developing ovarian follicles (cyclic rats), and two groups with both
      increased sex hormone concentrations and the presence of developing ovarian
      follicles (day 14 pregnant rats treated with FSH and day 21 pregnant rats). Rats
      were infused for 1h with either saline or endotoxin (1 microg/kg body weight) and
      sacrificed 4h after the infusion. Kidney sections were snap-frozen and prepared
      for immunohistochemistry. Endotoxin-induced glomerular granulocyte infiltration
      was increased only in the groups of rats with increased progesterone and/or
      17beta-oestradiol concentrations. This could be due to endotoxin-induced ICAM-1
      and/or VCAM-1 expression, which was observed in all endotoxin-treated groups and
      in all endotoxin-treated groups with increased sex hormone concentrations,
      respectively. It could also be due to an effect on granulocytes per se, since the
      number of endotoxin-induced CD11b-positive cells in the glomeruli was increased
      only in the groups with increased sex hormone concentrations. Endotoxin-induced
      glomerular monocyte infiltration, however, was seen only in those groups in which
      developing ovarian follicles were lacking (i.e. day 14 pregnant, pseudopregnant
      and lactating rats), suggesting that developing ovarian follicles produce anti
      inflammatory factors. These factors did not have an effect on endothelial or
      leukocyte adhesion molecule expression. We hypothesize that the presence of
      elevated progesterone concentrations increased the endotoxin-induced glomerular
      granulocyte infiltration, while endotoxin-induced glomerular monocyte
      infiltration was inhibited in the presence of developing ovarian follicles.

PMID- 16406117
TI  - Morbidity in 3-7-month-old dairy calves in south-western Sweden, and risk factors
      for diarrhoea and respiratory disease.
AB  - The health status of 2947 heifer calves born in 1998 and raised in 122 Swedish
      dairy herds was monitored from birth to 210 days of age. Disease occurrence was
      recorded by farmers and by veterinarians who visited the farms six times yearly,
      examined the calves clinically and auscultated their lungs. The incidence risks
      of diarrhoea, ringworm and clinical respiratory-tract disease (CRTD) in calves
      from 3 to 7 months of age were 2.7%, 5.6% and 5.7%, respectively. The herd-level
      incidence risks of the three diseases were zero in 63.1%, 76.2% and 48.4%,
      respectively, of the herds. In positive herds incidence risks were 2.2-46.4%, 2.6
      47.0% and 2.2-53.3%, respectively. The associations between the potential risk
      factors age at first grazing, air quality, birth place, feeding of colostrum,
      hygiene, number of animals, age range within the pen or building, pen area, pen
      location, previous housing type, present housing type, previous disease and
      season, and each of three binary outcome variables (diarrhoea, increased
      respiratory sounds and CRTD) were evaluated using two-level (calf; herd) variance
      component logistic models. Predictors significantly associated (P<0.05) with
      diarrhoea were pen area, season and the interaction between pen location and
      previous CRTD. Previous CRTD, season and heart girth at weaning were
      significantly associated with moderately to severely increased respiratory
      sounds. Predictors significantly associated with CRTD were previous diarrhoea,
      previous housing and season. It was concluded that the incidence of diarrhoea and
      CRTD in 91-210-day-old Swedish dairy calves is higher than previously reported
      from dairy herds in Sweden and the USA, and that diarrhoea, increased respiratory
      sounds and CRTD are associated with season, a history of disease during the first
      90 days of age and, to some extent, housing factors.

PMID- 16406116
TI  - Fruit and vegetable intake: Few adolescent girls meet national guidelines.
AB  - OBJECTIVE: To examine longitudinal changes in daily fruit and vegetable
      consumption among black and white adolescent girls and calculate the percent of
      girls who met the Healthy People 2010 recommendations. METHODS: Girls (1186 black
      and 1126 white) who participated in the National Heart, Lung, and Blood Institute
      Growth Health Study (NGHS) were included if they had completed a 3-day food diary
      for at least one of six annual assessments visits, beginning at ages 11 or 12.
      Mixed models estimated the association of visit and race with (a) average daily
      consumption of fruits and vegetables and (b) the probability of meeting intake
      recommendations on one or more out of 3 days. RESULTS: For girls of both races,
      fruit and vegetable consumption increased with age; white girls showed a greater
      increase in fruit and nutrient-rich vegetable intake than black girls. Across
      visits, girls consumed considerably fewer than the recommended daily servings of
      fruits (1.0-1.5), vegetables (1.7-2.5), or nutrient-rich vegetables (0.25). Most
      girls (95%) failed to meet Healthy People 2010 recommendations. CONCLUSIONS:
      Public health efforts are needed to meet Healthy People 2010 objectives.

PMID- 16406119
TI  - Synthetic promoter libraries--tuning of gene expression.
AB  - The study of gene function often requires changing the expression of a gene and
      evaluating the consequences. In principle, the expression of any given gene can
      be modulated in a quasi-continuum of discrete expression levels but the
      traditional approaches are usually limited to two extremes: gene knockout and
      strong overexpression. However, applications such as metabolic optimization and
      control analysis necessitate a continuous set of expression levels with only
      slight increments in strength to cover a specific window around the wild-type
      expression level of the studied gene; this requirement can be met by using
      promoter libraries. This approach generally consists of inserting a library of
      promoters in front of the gene to be studied, whereby the individual promoters
      might deviate either in their spacer sequences or bear slight deviations from the
      consensus sequence of a vegetative promoter. Here, we describe the two different
      methods for obtaining promoter libraries and compare their applicability.

PMID- 16406118
TI  - Breakdown of the blood brain barrier and blood-cerebrospinal fluid barrier is
      associated with differential leukocyte migration in distinct compartments of the
      CNS during the course of murine NCC.
AB  - Brain homeostasis is normally protected by the blood brain barrier (BBB) and the
      blood-cerebrospinal fluid barrier (BCB), barriers that function in distinct CNS
      compartments and consist of different types of blood vessels including pial
      (subarachnoid spaces, leptomeninges), parenchymal (cerebral cortex) and
      ventricular vessels. In this study, a mouse model of neurocysticercosis was used
      to distinguish between changes in the permeability of the BBB and the BCB and
      determine the association of such alterations on leukocyte infiltration. Mice
      were intracranially infected with the parasite Mesocestoides corti and sacrificed
      at various times post infection. Different anatomical areas of infected brain
      were analyzed by three color immunofluoresence utilizing antibodies against serum
      proteins to assess brain barrier permeability, glial fibrillary acidic protein
      (GFAP) to detect astrocytes, and specific cell surface markers to determine the
      subpopulations of leukocytes infiltrating the CNS at particular sites. The
      results indicate increased permeability of all three types of vessels/structural
      sites as a result of infection evidenced by serum proteins and leukocyte
      extravasation but with considerable differences in the timing and extent of these
      permeability changes. Parenchymal vessels were the most resilient to changes in
      permeability whereas pial vessels were the least. Choroid plexus vessels of the
      ventricles also appeared less susceptible to increased permeability compared with
      pial vessels. In addition, parenchymal vessels appeared impermeable to particular
      types of immune cells even after extended periods of infection. Additionally,
      alterations in reactive astrocytes juxtaposed to blood vessels that exhibited
      increased permeability displayed increased expression of cytokines known to
      regulate brain barrier function. The results suggest that access of leukocytes
      and serum derived factors into the infected brain depend on several parameters
      including the anatomical area, type of vascular bed, cell phenotype and cytokine
      microenvironment.

PMID- 16406120
TI  - The effects of thermocycling on the flexural strength and flexural modulus of
      modern resin-based filling materials.
AB  - OBJECTIVE: Evaluation of flexural strengths and flexural moduli of hybrids,
      packables, ormocers, compomers and flowables prior to, and after, thermocycling.
      MATERIALS AND METHODS: Twenty specimens, size (25 +/- 2) mm x (2 +/- 0.1) mm x
      (2+/-0.1) mm, of Herculite (HE), Point 4 (P4), TetricCeram (TC), Miris (MI),
      TetricCeram HB, (HB), Solitaire 2 (SO), Surefil A (SU), Definte (DE), Admira
      (AD), Dyract AP (DY), Compoglass (CO) and TetricFlow (TF) were made according to
      ISO 4049. A three-point-bending test was carried out for the first 10 specimens
      after 24 h water storage at 37 degrees C and for the second 10 specimens after 30
      day water storage at 37 degrees C, followed by 5000 thermocycles between +5 and
      +55 degrees C. For each test series flexural strengths and flexural moduli were
      calculated. Statistical significance was p < 0.05. RESULTS: Flexural strengths of
      DY and CO missed the 80 MPa limit of ISO 4049 for occlusal fillings prior to and
      after thermocycling. AD missed it after thermocycling. HE, P4, TC, MI, HB, SO,
      SU, DE and TF did not significantly differ prior to and after thermocycling.
      Flexural strength of SO and AD significantly decreased after thermocycling. No
      change of the flexural moduli could be observed for any of the test materials.
      Only SU exceeded 10,000 MPa prior to and after thermocycling. SIGNIFICANCE: Only
      DY and CO missed the flexural strength limit of ISO 4049 for occlusal fillings.
      Only SU exceeded a flexural modulus of 10,000 MPa prior to and after
      thermocycling.

PMID- 16406121
TI  - Ontogeny of the common carp (Cyprinus carpio L.) innate immune system.
AB  - The ontogeny of the teleost innate immune system was studied in carp using
      cellular, histological and quantitative molecular techniques. Carp myeloid cells
      first appeared ventro-lateral of the aorta at 2 days post fertilization (the
      start of hatching), and subsequently around the sinuses of the vena cardinalis
      (or posterior blood islet), head kidney and trunk kidney. In addition, the
      hematopoietic tissue around the sinuses of the vena cardinalis transformed into
      that of the trunk kidney, which is the first description of the ontogeny of the
      trunk kidney hematopoietic tissue in teleosts. The mAb's used in this study
      reacted with carp myeloid surface molecules that are already transcribed and
      processed from the first appearance of myeloid cells, and thus serve a
      significant role in unraveling ontogenetic processes of teleost immunology.
      Finally, this study associated the first appearance of myeloid cells with an
      immune response on the molecular level: 2 days post fertilization embryos
      responded to LPS injection with upregulation of interleukin 1-beta, inducible
      nitric oxide synthase and serum amyloid A, and down-regulation of complement
      factor 3 and alpha2-macroglobulin, implying a functional embryonic innate defense
      system.

PMID- 16406122
TI  - Preface: psychophysiology and cognitive neuroscience.
AB  - The intersection of psychophysiology and cognitive neuroscience has proved to be
      fertile ground for advancing our understanding of the neurobiological basis of
      behavior. The eight original empirical articles in this special issue contribute
      a variety of new evidence for how various bodily processes interrelate with brain
      processes, especially in the service of emotions and feelings. The findings are
      rich in their own right, and they also underscore the value of
      psychophysiological approaches in the investigation of brain-behavior
      relationships. This type of work is helping to shape a new field of "affective
      neuroscience."

PMID- 16406123
TI  - The role of oral fluid intake following adeno-tonsillectomy.
AB  - OBJECTIVE: To compare the incidence of complications following pediatric adeno
      tonsillectomy (T&A) in patients who are encouraged to drink oral liquid versus
      patients who drink on a voluntary basis. METHODS: This is a prospective,
      randomized, non-blinded study performed in a tertiary care medical center. Ninety
      three otherwise healthy pediatric patients aged 2-12 years undergoing ambulatory
      T&A by a single surgeon were included in the study. Forty four patients were
      encouraged to drink 240 ml of clear liquid prior to discharge while 49 patients
      drank on a voluntary basis. Patients were followed prospectively for the
      incidence of emesis, dehydration and other complications. RESULTS: Overall,
      emesis was experienced by 18% of patients in the post anesthesia care unit (PACU)
      and by 20% at home. Fifty percent of patients in the encouraged group versus 31%
      in the voluntary group reached the goal volume of oral liquids (p<0.05). The
      incidence of emesis was higher in both the encouraged (41% versus 14%) and
      voluntary group (40% versus 26%) when the goal volume of 240 ml was reached.
      There was no statistically significant difference between the two groups in terms
      of duration of PACU stay, incidence of emesis, number of episodes of emesis or
      volume of emesis. Further, there was no difference between the two groups in
      terms of post-operative complications including dehydration. CONCLUSIONS: The
      current practice of a mandatory trial of oral fluid intake in the post-operative
      period may not be a necessary requirement for discharge. Further, mandatory oral
      fluids may result in a higher incidence of emesis.

PMID- 16406124
TI  - Prevalence of middle ear pathologies in children with bilateral sensorineural
      hearing loss.
AB  - OBJECTIVES: In poor countries, hearing aids are too expensive for sensorineural
      hearing loss (SNHL) children's parents to offer for their children. These
      children may have middle ear problem, this will aggravate the level of hearing
      loss which may lead to delay in their ability to speak. This study is to
      highlight the prevalence of middle ear pathology in SNHL children. METHODS: Two
      hundred children with bilateral sensorineural hearing loss (SNHL) were selected
      in our study from the outpatient clinic of ENT department of Sohag University
      Hospital, Egypt. Children were classified into three categories according to
      their middle ear status. They were normal middle ear, middle ear with unhealthy
      tympanic membrane or otitis media with intact drum and chronic suppurative otitis
      media with perforation. RESULTS: Seventy percent of cases were normal, 25% had
      middle ear problem with intact tympanic membrane and 5% had chronic suppurative
      otitis media with perforation. CONCLUSION: Thirty percent of SNHL children have
      middle ear pathology which aggravate the degree of hearing loss. Regular
      evaluation of SNHL children to treat those having middle ear pathology medically
      and/or surgically and this may help those having no ability to have hearing aids
      to learn language early.

PMID- 16406125
TI  - Induction of chemokine receptor expression during early stages of T cell
      development.
AB  - The early events in T lineage commitment are difficult to study because of the
      rarity of these cells. We have therefore used cloned Pax5-/- pre-BI cell lines as
      a model system to study this. Stimulation in vitro of Pax5-/- pre-BI cells with
      stromal cells expressing the Notch ligand Delta-like 1 results in them
      coincidently undergoing some of the phenotypic and functional changes associated
      with early T cell commitment. Kinetic analysis indicated that there was a rapid
      induction of transcripts for the two chemokine receptors CCR4 and CXCR6.
      Transcripts for CCR8 increased with slower kinetics. Migration assays indicated
      that Delta-like 1 signalling of Pax5-/- pre-BI cells had induced responsiveness
      to the chemokines MDC and MIP-1beta, ligands for the receptors CCR4 and CCR8,
      respectively. Importantly, following Delta-like 1 signalling, similar increases
      in chemokine receptor transcripts were seen in a recently described bone marrow
      progenitor subpopulation having significant T cell progenitor activity and being
      phenotypically and functionally similar to Pax5-/- pre-BI cells. The relevance of
      these findings to studies of early T cell development will be discussed.

PMID- 16406127
TI  - Metabolic syndrome by the international diabetes federation definition in Hong
      Kong Chinese.
AB  - In this report, we aimed to examine the impact of the new International Diabetes
      Federation (IDF) definition on the prevalence and clinical characteristics of
      subjects with metabolic syndrome (MES). Data were obtained from a prevalence
      survey for cardiovascular risk factors in a Hong Kong Chinese working population.
      There were 1513 subjects well representing all occupational groups from managers
      to general laborers [910 (60.1%) men and 603 (39.9%) women (mean age 37.5+/-9.2,
      median 37.0, range 18-66 years)]. The crude prevalence of MES defined by the IDF
      criterion was 7.4% (compared to other criteria: NCEP, 9.6%; WHO, 13.4% and EGIR,
      8.9%). The age-standardized prevalence of MES by the IDF criterion was 8.8% in
      women and 7.3% in men. Subjects with MES defined by IDF criterion had higher body
      mass index and waist compared to those with MES defined by NCEP or WHO criteria,
      and lower triglyceride compared to those with MES defined by NCEP criterion after
      adjustment for age, gender and smoking. Non-MES subjects defined by IDF criterion
      had higher 2h glucose and insulin resistance compared to non-MES subjects defined
      by WHO. In conclusion, the new IDF criterion for MES is easy to implement in
      clinical practice. It may be potentially more 'specific' in identifying subjects
      with MES although compared to the NCEP criterion, it may have missed a proportion
      of subjects, especially men, who have metabolic derangement. Prospective and
      interventional studies are needed to validate the prognostic values of this new
      definition in comparison with other existing definitions.

PMID- 16406129
TI  - Determining the region-specific contributions of 5-HT receptors to the
      psychostimulant effects of cocaine.
AB  - Cocaine is a drug of abuse that has complex neurochemical and behavioural
      profiles. When it became evident that models that involve only dopamine do not
      fully explain the complex effects of cocaine on behaviour, the focus of research
      expanded to include the 5-hydroxytryptamine (5-HT) system in the brain. The 5-HT
      system comprises several subtypes of 5-HT receptors, which contribute
      differentially to the various behavioural effects of cocaine. In this article, we
      describe which subtypes regulate behaviours that are related to cocaine addiction
      and how they might provide new therapeutic approaches. Numerous subpopulations of
      each 5-HT receptor can be distinguished according to their location in the brain.
      We also discuss how these subpopulations relate to the effects of 5-HT-receptor
      stimulation at the systemic level. These insights provide a new receptor-based
      approach for understanding the 5-HT mechanisms that subserve the actions of
      cocaine and possible pharmacotherapies against cocaine addiction.

PMID- 16406128
TI  - The effect of resistance versus aerobic training on metabolic control in patients
      with type-1 diabetes mellitus.
AB  - This study evaluated the effect of aerobic versus resistance training on
      metabolic control in type-1 diabetes patients. Thirteen non-active patients,
      ranging in age from 13-30, were submitted to a 12-week aerobic exercise (Group A,
      n = 7) or resistance training (Group B, n = 6) period. Group A training consisted
      of a 40 min walk or run and Group B training consisted of resistance exercises
      three times a week. Blood samples were obtained before and after the 12-week
      training period. When these samples were compared, results showed that in Group A
      there were no changes in glycated hemoglobin, lipid profile, fast glucose level
      or body mass index (BMI). There was, however, a reduction in waist circumference
      and in average self-monitored blood glucose levels, measured after each exercise
      session. In Group B, there were no changes in the parameters evaluated. In both
      groups the total insulin dosage was reduced. As other authors have shown,
      resistance/aerobic training did not improve glycated hemoglobin in type-1
      diabetes patients.

PMID- 16406130
TI  - Electroporation as a tool to transfer the plasmid pRL489 in Oscillatoria MKU 277.
AB  - To establish the gene transfer system in the cyanobacteria, we successfully
      introduced the shuttle plasmid pRL489 into Oscillatoria MKU 277 by
      electroporation with transformation frequencies of up to 102 cfu/mug of plasmid
      DNA. These findings suggest that Oscillatoria MKU 277 can be used as an
      experimental tool for genetic maneuvering.

PMID- 16406131
TI  - Introducing a complex health innovation--primary health care reforms in Estonia
      (multimethods evaluation).
AB  - All post-Soviet countries are trying to reform their primary health care (PHC)
      systems. The success to date has been uneven. We evaluated PHC reforms in
      Estonia, using multimethods evaluation: comprising retrospective analysis of
      routine health service data from Estonian Health Insurance Fund and health
      related surveys; documentary analysis of policy reports, laws and regulations;
      key informant interviews. We analysed changes in organisational structure,
      regulations, financing and service provision in Estonian PHC system as well as
      key informant perceptions on factors influencing introduction of reforms. Estonia
      has successfully implemented and scaled-up multifaceted PHC reforms, including
      new organisational structures, user choice of family physicians (FPs), new
      payment methods, specialist training for family medicine, service contracts for
      FPs, broadened scope of services and evidence-based guidelines. These changes
      have been institutionalised. PHC effectiveness has been enhanced, as evidenced by
      improved management of key chronic conditions by FPs in PHC setting and reduced
      hospital admissions for these conditions. Introduction of PHC reforms - a complex
      innovation - was enhanced by strong leadership, good co-ordination between policy
      and operational level, practical approach to implementation emphasizing
      simplicity of interventions to be easily understood by potential adopters, an
      encircling strategy to roll-out which avoided direct confrontations with narrow
      specialists and opposing stakeholders in capital Tallinn, careful change
      management strategy to avoid health reforms being politicized too early in the
      process, and early investment in training to establish a critical mass of health
      professionals to enable rapid operationalisation of policies. Most importantly, a
      multifaceted and coordinated approach to reform - with changes in laws;
      organisational restructuring; modifications to financing and provider payment
      systems; creation of incentives to enhance service innovations; investment in
      human resource development - was critical to the reform success.

PMID- 16406132
TI  - Immunization coverage in Mozambique: from concepts to decision-making.
AB  - Immunization is an effective strategy to reduce morbidity and mortality among
      children. This recognition has led many countries to concentrate efforts in
      establishing desirable achievements in the form of immunization coverage figures.
      However, less focus has been placed on effort made by different countries to
      attain high immunization coverage. During August 2002, 14 district health
      directors in a remote province of Mozambique (Niassa) were interviewed. The
      objective was to ascertain the construction of immunization coverage and how they
      implement the desired program strategies in order to improve the health status of
      the region. We found that most managers regarded the immunization coverage as
      data and thus high coverage as an end in itself, rather than as a reflection of
      the reality. We also found that there are uncertainties in population data which
      makes it difficult to plan activities bellow the level of a district. We argue
      further that the innovative distinction between the views proposed on the
      immunization coverage, provided us with an insight of the different challenges
      that district health directors face as leaders of the district health management
      team in Niassa. Clues on the implications of certain views of immunization
      coverage for policy and local decision-making in the national and global pursuit
      of immunization targets are provided.

PMID- 16406133
TI  - Stroke severity and early recovery after first-ever ischemic stroke: results of a
      hospital-based study in Taiwan.
AB  - OBJECTIVE: To assess the relationship between admission stroke severity and
      outcomes of acute hospitalization in patients with first-ever ischemic stroke in
      Taiwan. METHODS: Data were prospectively collected from 360 first-ever ischemic
      stroke patients admitted to a medical center within 48h of stroke onset. Stroke
      severity was evaluated with NIH stroke scale (NIHSS) and categorized as mild (0
      6), moderate (7-15), or severe (16-38). We studied three prespecified discharge
      outcomes: (1) status based on a combination of NIHSS and modified Barthel index
      (MBI), (2) subsequent change in neurologic impairments, and (3) subsequent change
      in functional status. For each outcome, a separate polytomous logistic regression
      model with least favorable category as the reference group was constructed,
      controlling confounding factors. RESULTS: Patients (58% male) had mean age 64.9+/
      12.5 (range 18-90), median NIHSS 6 and median MBI 12 on admission. Median length
      of-stay was 7 (range 1-122) days; in-hospital deaths 8%. Twenty-two percent
      patients had excellent status outcome, 33% good. For subsequent change in
      neurologic impairments, 22% of patients had better outcomes; for sequent change
      in functional status, better outcomes were noted in 14% of patients. The NIHSS
      score at admission was strongly associated with outcomes of acute hospitalization
      after multivariate adjustment. The odds ratio (OR) for moderate (versus mild)
      stroke patients to achieve excellent status was 0.04 (95% CI, 0.02-0.10), and for
      severe stroke the OR was less than 0.01 (95% CI, 0-0.05). The OR (95% CI) for
      moderate stroke patients to have good or improved outcome was 0.19 (0.10-0.36),
      for severe stroke 0.04 (0.01-0.13). The ORs for moderate and severe (versus mild)
      stroke patients to have better subsequent change in neurologic impairments were
      5.18 (1.94-13.85) and 4.12 (1.38-12.30); to remain stationary 0.43 (0.19-0.96)
      and 0.15 (0.06-0.36), respectively. CONCLUSIONS: In patients with first-ever
      ischemic stroke in Taiwan, admission NIHSS is predictive of outcome of acute
      hospitalization.

PMID- 16406134
TI  - Development of an ID-ELISA for the detection of Rice black-streaked dwarf virus
      in plants.
AB  - The Rice black-streaked dwarf virus (RBSDV) virion is composed of two layers of
      capsid proteins and 10 segments of double-stranded genomic RNA (S1-S10). Due to
      the fragility of the RBSDV outer capsid, it is very difficult to obtain intact
      virus particles for preparation of antiserum needed in virus detection. In this
      work, the major outer capsid protein (P10) encoded by S10 of RBSDV was expressed
      in Escherichia coli cells as a glutathione-S-transferase (GST) fusion protein.
      After purification of GST-P10 through affinity chromatography, P10 was released
      from the fusion protein by thrombin digestion and the purified P10 protein was
      used to immunize rabbits. The resulting polyclonal antiserum specifically
      recognized RBSDV from infected plant tissue and a planthopper vector in Western
      blotting assays. To facilitate screening of large numbers of samples, an indirect
      enzyme-linked immunosorbent assay (ID-ELISA) protocol capable of detecting RBSDV
      in very dilute wheat leaf extracts was developed. Based on the results, we
      conclude that efficient and economic detection of RBSDV can be performed
      routinely using polyclonal antiserum against P10 expressed in prokaryotic cells.

PMID- 16406135
TI  - Predicting the thermal inactivation of bacteria in a solid matrix: simulation
      studies on the relative effects of microbial thermal resistance parameters and
      process conditions.
AB  - A combined mathematical model for predicting heat penetration and microbial
      inactivation in a solid body heated by conduction was tested experimentally by
      inoculating agar cylinders with Salmonella typhimurium or Enterococcus faecium
      and heating in a water bath. Regions of growth where bacteria had survived after
      heating were measured by image analysis and compared with model predictions.
      Visualisation of the regions of growth was improved by incorporating chromogenic
      metabolic indicators into the agar. Preliminary tests established that the model
      performed satisfactorily with both test organisms and with cylinders of different
      diameter. The model was then used in simulation studies in which the parameters
      D, z, inoculum size, cylinder diameter and heating temperature were
      systematically varied. These simulations showed that the biological variables D,
      z and inoculum size had a relatively small effect on the time needed to eliminate
      bacteria at the cylinder axis in comparison with the physical variables heating
      temperature and cylinder diameter, which had a much greater relative effect.

PMID- 16406136
TI  - Maspin gene expression is a significant prognostic factor in resected non-small
      cell lung cancer (NSCLC). Maspin in NSCLC.
AB  - Maspin is a member of the serpin (serine protease inhibitor) superfamily, and
      some experimental studies revealed a potential tumor suppressor activity of
      maspin. To reveal clinical significance of maspin status in non-small cell lung
      cancer (NSCLC), we quantitatively evaluated maspin gene expression in lung
      primary tumors cut from a total of 55 resected NSCLC patients. Maspin expression
      in squamous cell carcinoma (Sq) was significantly higher than that in
      adenocarcinoma (Ad, p=0.011). Five-year overall survival rates of maspin-high and
      maspin-low patients were 67.7 and 41.4%, respectively, demonstrating a
      significant favorable prognosis of maspin-high patients (log-rank, p=0.042). A
      multivariate analysis confirmed that high maspin expression was an independent
      and significant factor to predict a favorable overall survival (p=0.031). These
      results suggested that maspin expression was significantly increased in Sq than
      in Ad, and that increased maspin expression was a significant factor to predict a
      favorable prognosis in resected NSCLC.

PMID- 16406137
TI  - Promising results achieved with a combination of chemotherapy and two retinoids
      in patients with advanced non-small-cell lung cancer.

PMID- 16406138
TI  - Nutritional homeostasis and indispensable amino acid sensing: a new solution to
      an old puzzle.
AB  - Indispensable amino acids are neither synthesized nor stored in animals and are
      rapidly depleted when not provided by the diet. To maintain homeostasis,
      organisms must sense deficiency of an indispensable amino acid and implement a
      repletion strategy. In rats and birds, the anterior piriform cortex houses the
      detector, but its mechanism has evaded description for >50 years. Recently, rapid
      detection of amino acid depletion was shown behaviorally when naive animals, pre
      fed a low nitrogen diet, terminated their first deficient meal within 20 min. The
      general amino acid control system of yeast, which is activated by amino acid
      deprivation via deacylated tRNA, was found to be active in rodent brain, showing
      conservation of amino acid sensory mechanisms across eukaryotic species.

PMID- 16406139
TI  - Infection risk associated with a closed luer access device.
AB  - The potential for microbial contamination associated with a recently developed
      needleless closed luer access device (CLAD) (Q-Syte; Becton Dickinson, Sandy, UT,
      USA) was evaluated in vitro. Compression seals of 50 multiply activated Q-Syte
      devices were inoculated with Staphylococcus epidermidis NCTC 9865 in 25% (v/v)
      human blood and then disinfected with 70% (v/v) isopropyl alcohol followed by
      flushing with 0.9% (w/v) sterile saline. Forty-eight of 50 (96%) saline flushes
      passed through devices that had been activated up to a maximum of 70 times
      remained sterile. A further 25 Q-Syte CLADs that had undergone multiple
      activations were challenged with prefilled 0.9% (w/v) sterile saline syringes,
      the external luer tips of which had been inoculated with S. epidermidis NCTC 9865
      prior to accessing the devices. None of the devices that had been accessed up to
      70 times allowed passage of micro-organisms, despite challenge micro-organisms
      being detected on both the syringe tip after activation and the compression seals
      before decontamination. These findings suggest that the Q-Syte CLAD may be
      activated up to 70 times with no increased risk of microbial contamination within
      the fluid pathway. The device may also offer protection from the external surface
      of syringe tips contaminated with micro-organisms.

PMID- 16406140
TI  - Are in vitro hepatitis B core promoter mutations important for clinical
      alterations in viral load?
AB  - In vitro studies of HBV core promoter mutations in hepatoma cell lines suggest
      that some mutations in core promoter transcription factor binding sites result in
      reduced core promoter activity and viral replication. We sought to validate this
      hypothesis using clinical samples with viral load differences before and after
      HBeAg seroconversion. A consensus sequence for transcription factor binding
      sites/regulatory regions was constructed based on published studies. Serum from
      two time points in 33 seroconverters and 10 interferon non-responders (controls)
      were utilized. Genotyping, HBV DNA quantification and direct sequencing of core
      promoter were performed. There were 216 new mutations following HBeAg
      seroconversion but few in controls. Mutations or mismatches to consensus
      transcription factor/regulatory region sequences clustered at nucleotide
      positions appeared genotype-specific, non-group specific or baseline mismatches
      and were discounted as having significant impact on viral replication. Only a few
      mutations in three seroconverters (9.1%) were specific, while 39.4% had no new
      mutations that could be attributed to reduction in viral load following HBeAg
      seroconversion. In 51.5% of patients, mutations were of uncertain significance
      because they occurred in demonstrated non-critical clustered nucleotide
      positions. Core promoter mutations post-seroconversion did not correlate with in
      vitro induced mutations that reduced the promoter activity.

PMID- 16406141
TI  - Angiotensin converting enzyme has an inhibitory role in CGRP metabolism in human
      skin.
AB  - The neutral endopeptidase (NEP) is important for calcitonin gene related peptide
      (CGRP) degradation, while the role of angiotensin converting enzyme (ACE) remains
      unclear. By using dermal microdialysis we explored the effect of phosphoramidon
      (NEP blocker), captopril (ACE blocker) and a mixture of both drugs on the
      intensity of electrically-induced CGRP-mediated neurogenic flare. The results
      reveal that phosphoramidon elevated flare intensity, but that this was not
      further increased by adding captopril. In contrast, neurogenic flare was
      decreased when the drug mixture was applied in compared to NEP only. Electrically
      released CGRP levels could be measured directly in perfusates containing
      phosphoramidon and the mixture. Again, CGRP levels were elevated in
      phosphoramidon treated sites, and significantly reduced upon adding captopril.
      These findings suggest that NEP and ACE do not have additive effects regarding
      neuropeptide degradation. In contrast, inhibition of ACE seems to augment CGRP
      catabolism.

PMID- 16406142
TI  - Dimerization of the melanocortin 4 receptor: a study using bioluminescence
      resonance energy transfer.
AB  - The melanocortin 4 receptor is important in the regulation of satiety. In this
      study we have investigated the propensity of the MC4 receptor to homodimerize.
      MC4 receptors with either a modified green fluorescent protein (GFP(2)) or
      Renilla luciferase (RLuc) at their C-terminus were constructed. These receptors
      showed equivalent binding and functional properties to the wild-type MC4
      receptor. Bioluminescence resonance energy transfer readings indicated that the
      MC4 receptor exists as a constitutive homodimer, which was not regulated by
      peptide interaction. The efficiency of MC4 receptor to form homodimers was
      greatly enhanced compared to its ability to heterodimerize with the kappa opioid
      receptor.

PMID- 16406143
TI  - Antimicrobial activity of glycosidase inhibitory protein isolated from
      Cyphomandra betacea Sendt. fruit.
AB  - Broad-spectrum antimicrobial activity of an invertase inhibitory protein (IIP)
      isolated from Cyphomandra betacea ripe fruits is documented. Minimal inhibitory
      concentration (MIC) values were determined by agar macrodilution and broth
      microdilution assays. This IIP inhibited the growth of xylophagous and
      phytopatogenic fungi (Ganoderma applanatum, Schizophyllum commune, Lenzites
      elegans, Pycnoporus sanguineous, Penicillium notatum, Aspergillus niger,
      Phomopsis sojae and Fusarium mango) and phytopathogenic bacteria (Xanthomonas
      campestris pvar vesicatoria CECT 792, Pseudomonas solanacearum CECT 125,
      Pseudomonas corrugata CECT 124, Pseudomonas syringae pv. syringae and Erwinia
      carotovora var carotovora). The IIP concentration required to completely inhibit
      the growth of all studied fungi ranged from 7.8 to 62.5 microg/ml. Phytopatogenic
      bacteria were the most sensitive, with MIC values between 7.8 and 31.25
      microg/ml. Antifungal and antibacterial activities can be associated with their
      ability to inhibit hydrolytic enzymes. Our results indicate the possible
      participation of IIP in the plant defense mechanism and its potential application
      as a biocontrol agent against phytopathogenic fungi and bacteria.

PMID- 16406144
TI  - [Anti-TNF therapy: contraindication or promising treatment in lupus?].

PMID- 16406145
TI  - Task specific adaptations in rat locomotion: runway versus horizontal ladder.
AB  - In walking quadrupeds the alternating activity pattern of antagonistic leg
      muscles and the coordination between legs is orchestrated by central pattern
      generating networks within the spinal cord. These networks are activated by tonic
      input from the reticular formation in the brainstem. Under more challenging
      conditions, such as walking on a horizontal ladder, successful locomotion relies
      upon additional context dependent input from pathways such as the cortico- and
      rubro-spinal tracts. In this study we used electromyographic and kinematic
      approaches to characterize the adaptations in the walking pattern in adult
      uninjured rats crossing a horizontal ladder. We found that the placement of a
      hind limb on a rung precisely followed the placement of the ipsilateral fore
      limb. This is different to normal walking where the hind limb is placed behind
      the position of the ipsilateral fore limb. The increased reach of the hind limbs
      is achieved by increased flexion of the hip and rotation of the pelvis during the
      swing phase. Electromyographic observations showed decreased burst duration in
      Tibialis anterior an ankle flexor muscle. Further changes in the muscle activity
      pattern were likely due to the reduced stepping frequency during ladder walking.
      Following a lesion of the dorsal column, containing major parts of the
      corticospinal tract, we found an increased number of stepping errors and changes
      in the stepping strategy. The step length of the fore limbs was reduced and the
      hind limbs were frequently positioned on rungs other than those occupied by the
      fore limb.

PMID- 16406146
TI  - Dopamine transporter-mediated cytotoxicity of 6-hydroxydopamine in vitro depends
      on expression of mutant alpha-synucleins related to Parkinson's disease.
AB  - 6-Hydroxydopamine (6-OHDA) is widely used to produce animal models of Parkinson's
      disease (PD) by selectively destroying the nigro-striatal dopaminergic systems,
      but selective toxicity of 6-OHDA towards dopaminergic cells in vitro remains
      controversial. Mutant (A30P and A53T) alpha-synuclein isoforms cause increased
      vulnerability of cells towards various toxic insults and enhance dopamine
      transporter (DAT)-mediated toxicity of the selective dopaminergic neurotoxin and
      mitochondrial complex I inhibitor MPP(+) in vitro. Here we extend our recent
      studies on DAT-mediated toxicity to elucidate the mechanisms involved in
      selective dopaminergic toxicity of 6-OHDA. We studied the cytotoxicity as well as
      the toxic mechanisms of 6-OHDA in human embryonic kidney HEK-293 cells
      ectopically co-expressing mutant alpha-synucleins and the human DAT protein. 6
      OHDA showed half-maximal toxic concentration (TC(50)) of 88 microM in HEK-hDAT
      cells without alpha-synuclein expression after 24 h, whereas the TC(50) values
      significantly decreased to 58 and 39 microM by expression of A30P and A53T alpha
      synuclein, respectively. alpha-Synuclein expression did not affect 6-OHDA
      toxicity in HEK-293 cells not expressing the DAT. Analysis of intracellular
      parameters of cellular energy metabolism revealed that the co-expression of
      mutant alpha-synucleins in HEK-hDAT cells accelerates the reduction of
      intracellular net ATP levels and ATP/ADP ratios induced by 6-OHDA. Uptake
      function of the DAT was not altered by expression of alpha-synuclein isoforms.
      Our data suggest a mechanism of 6-OHDA-induced dopaminergic toxicity involving an
      interaction of mutant alpha-synucleins with the DAT molecule and subsequent
      acceleration of cellular energy depletion that might be relevant for the
      pathogenesis of PD.

PMID- 16406148
TI  - Effects of BDNF infusion on the axon terminals of locus coeruleus neurons of
      aging rats.
AB  - Using in vivo electrophysiological techniques and continuous local infusion
      methods, we examined the effects of brain-derived neurotrophic factor (BDNF) and
      its specific antibody (anti-BDNF) on the noradrenergic axon terminals of the
      locus coeruleus (LC) neurons in the frontal cortex of aging rats. Recently, we
      observed that LC neurons with multiple-threshold antidromic responses (multi
      threshold LC neurons) increased critically between 15 and 17 months of age. To
      examine whether the BDNF is involved in this change occurred in the aging brain,
      we continuously infused BDNF into the frontal cortex for 14 days. Exogenous BDNF
      produced a marked increase in the multi-threshold LC neurons in the 13-month-old
      brain, accompanied with a decrease in threshold current. However, no
      morphological change in the noradrenergic axons was observed in the BDNF-infused
      cortex. In contrast, infusion of anti-BDNF led to a dose-dependent reduction of
      the multi-threshold LC neurons in the 19-month-old brain, accompanied with an
      increase in threshold current. These findings suggest that BDNF may contribute to
      functional changes in the presynaptic axon terminals of LC neurons in the aging
      brain.

PMID- 16406147
TI  - DNA prime/protein boost immunization against HIV clade C: safety and
      immunogenicity in mice.
AB  - The induction of both cellular and humoral immunity is an important goal for
      vaccine development against HIV. As a step towards the development of an
      efficacious vaccine against HIV clade C, the world's most prevalent strain, a
      combination DNA prime/protein boost immunization strategy was tested. A DNA
      expression vector was prepared encoding a codon-optimized env gene derived from a
      pediatric HIV clade C isolate, 1084i. Mice were immunized with HIV1084i env
      encoding DNA, then boosted with homologous 1084i gp160. HIV1084i Env-specific T
      cell responses were induced with DNA vaccination alone, but the strongest
      cellular immune responses were seen after boosting with gp160. Immunization with
      gp160 alone induced high-titer antibodies but required two inoculations. In
      contrast, high-titer antibodies were seen after a single 1084i gp160 boost in DNA
      primed animals. All animals given gp160 inoculations, whether DNA primed or not,
      developed neutralizing antibodies reactive with HIV1084i and a macaque-passaged
      simian/human immunodeficiency construct, SHIV-1084ip. The results demonstrate the
      utility of this DNA prime/protein boost approach to generate cellular immunity,
      as well as neutralizing antibodies, against HIV clade C env antigens.

PMID- 16406149
TI  - Age-dependent interactive changes in serotonergic and noradrenergic cortical axon
      terminals in F344 rats.
AB  - In the frontal cortex of aging rats, we found an increase in sprouting of the
      noradrenergic (NA) axons originated from the locus coeruleus (LC). The
      serotonergic (5-HT) axons originating from the dorsal raphe (DR) share the same
      cortical area and their age-dependent changes and interactions with NA axons were
      still unclear. To compare quantitatively the extent of axonal sprouting of DR and
      LC neurons in the frontal cortex, we extracellularly recorded from both DR and LC
      neurons in the same animals and antidromically stimulated 32 cortical sites (a
      pair of stimulating electrodes was moved at 100-mum intervals from 500 to 2000
      microm in depth). In addition, to examine the effects of degeneration of 5-HT
      axons on NA axons, and vice versa, we used specific neurotoxins for 5-HT (PCA) or
      NA (DSP-4) axons. We also used noradrenaline uptake inhibitor (maprotiline) to
      verify the effects of NA on degeneration of 5-HT axons. Results suggested that 5
      HT axons sprouted between 15 and 17 months of age and noradrenaline accelerated
      the age-dependent change of 5-HT axons.

PMID- 16406150
TI  - Increased levels of granular tau oligomers: an early sign of brain aging and
      Alzheimer's disease.
AB  - Development of neurofibrillary tangles (NFTs) is a pathological hallmark in
      various neurodegenerative disorders including Alzheimer's disease (AD). Recently,
      we identified a granular tau oligomer having a pre-filamentous structure. To
      determine the role of this oligomer in NFT formation, we quantified the amount of
      granular tau oligomer in 21 frontal cortex samples, each displaying varying
      degrees of Braak-staged NFT pathology. Here we report that granular tau oligomer
      levels in frontal cortex were significantly increased, even in brains displaying
      Braak-stage I neuropathology, a stage at which clinical symptoms of AD and NFTs
      in frontal cortex are believed to be absent. This suggests that increases in
      granular tau oligomer levels occur before NFTs form and before individuals
      manifest clinical symptoms of AD. Increased granular tau oligomer levels,
      therefore, may lead to NFT formation in frontal cortex, eventually leading to the
      development of AD. Thus, increases in granular tau oligomer levels may represent
      a very early sign of NFT formation and AD.

PMID- 16406151
TI  - Prenatal glucocorticoid exposure affects learning and vulnerability of
      cholinergic neurons.
AB  - Prenatal treatment with synthetic glucocorticoids is commonly used as a treatment
      for women at risk of preterm delivery. However, little is known about the life
      long consequences of these treatments on the fetus. In the present study, we
      evaluated cognitive function as well as susceptibility of cholinergic neurons to
      (192)IgG-saporin immunolesion in adult rats after prenatal glucocorticoid
      treatment. Morris water maze results revealed a significant difference in
      learning and memory function in adult rats that were prenatally exposed to
      dexamethasone, and further cognitive deficits after (192)IgG-saporin exposure.
      Choline acetyl transferase activity was decreased in the cortex of dexamethasone
      treated rats compared with controls. In addition, rats prenatally exposed to
      either dexa, or betamethasone revealed a dramatic decrease in choline acetyl
      transferase activity compared to control rats after (192)IgG-saporin lesion. We
      report behavioral and biochemical evidence for altered cognitive function and
      increased susceptibility of cholinergic neurons to (192)IgG-saporin in adult rats
      after prenatal glucocorticoid treatment. Taken together, these results suggest
      that prenatal treatment with dexamethasone could affect cognitive functions and
      render cholinergic neurons more vulnerable to challenges later in life.

PMID- 16406152
TI  - Interactive effects of fitness and hormone treatment on brain health in
      postmenopausal women.
AB  - Recent research in rodents suggests that extended and chronic hormone therapy can
      exacerbate memory impairments and irreversibly damage cells. However, aerobic
      fitness regimens have been shown to spare brain tissue and cognitive function. In
      addition, interactions between estrogen treatment and exercise have been reported
      in rodents. However, whether aerobic fitness and hormone treatments show
      interactive effects on human brain tissue and cognition has yet to be determined.
      Here we report two unique and important results: (a) HRT treatment up to 10 years
      in duration spares gray matter in prefrontal cortex and is associated with better
      performance on measures of executive function, whereas HRT treatment beyond 10
      years in duration increases the degree of prefrontal deterioration and amplifies
      the decline on measures of executive functioning (b) higher fitness levels
      augment the effects of shorter durations of hormone treatment and ameliorate the
      declines associated with prolonged hormone treatment.

PMID- 16406153
TI  - Memory activation enhances EEG abnormality in mild cognitive impairment.
AB  - This exploratory study investigated EEG power changes during memory activation in
      patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and
      16 age-matched controls underwent EEG registration during two conventional EEG
      conditions ('eyes closed' and 'eyes open') and three memory conditions ('word
      memory', 'picture memory' and 'animal fluency'). For all conditions, EEG power in
      the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands
      were expressed as percentile changes compared to 'eyes closed'. MCI patients
      showed significantly less decrease in the lower alpha band than controls (p=0.04)
      during picture memory activation. The word memory task showed a trend towards a
      similar effect (p=0.09). This study suggests that memory activation reveals EEG
      differences between MCI patients and controls while conventional EEG conditions
      do not.

PMID- 16406154
TI  - Atrophy rates of the cingulate gyrus and hippocampus in AD and FTLD.
AB  - This study explores the diagnostic utility of atrophy rates of the cingulate
      gyrus, its subdivisions and the hippocampus in Alzheimer's disease (AD) and
      frontotemporal lobar degeneration (FTLD). Regions were manually outlined on MR
      images of a group of pathologically or genetically confirmed patients with AD
      (n=19), FTLD (n=8) and age-matched controls (n=11). Mean (S.D.) atrophy rates
      (%year(-1)) in the cingulate in controls, AD and FTLD were -0.3 (1.2), 5.9 (3.5),
      and 8.6 (4.1), respectively. Hippocampal atrophy rates in controls, AD and FTLD
      were -0.1 (0.8), 3.4 (2.2), and 5.2 (5.4), respectively. Atrophy rates were
      significantly higher in the cingulate and hippocampi in AD and FTLD compared with
      controls (p<0.01). There was evidence of a difference in trends of atrophy in the
      cingulate (more anterior in FTLD and more posterior in AD) between the disease
      groups (p=0.03). Cingulate atrophy rates discriminated perfectly between FTLD and
      controls. Significantly better discrimination between AD and controls was
      obtained by hippocampal rather than cingulate rates. In conclusion, cingulate
      atrophy is as significant a feature of AD and FTLD as hippocampal atrophy.

PMID- 16406155
TI  - A study of daily and seasonal variations of radon concentrations in underground
      buildings.
AB  - A study of daily and seasonal variations of radon concentrations in underground
      buildings in major cities of China was carried out. According to the data from
      the Model 1027 continuous monitor, radon concentrations in the underground
      buildings changed through two cycles each day. The first cycle was from 12:00 to
      0:00 and the highest or lowest value, depending on location, was at about 19:00.
      The second cycle had a little change. Based on the data from solid state nuclear
      detectors (SSNTDs), it was concluded that the radon concentrations in underground
      buildings in winter were lower than in summer, which was opposite to that above
      the ground level. Similar to that above the ground level, the radon
      concentrations in spring were close to the year-round average radon
      concentrations.

PMID- 16406156
TI  - Direct capture of plasmid DNA from non-clarified bacterial lysate using
      polycation-grafted monoliths.
AB  - Monolith columns from macroporous polyacrylamide gel were grafted with
      polycations, poly(N,N-dimethylaminoethyl methacrylate) (polyDMAEMA), (2
      (methacryloyloxy)ethyl)-trimethyl ammonium chloride (polyMETA) and partially
      quaternized polyDMAEMA prepared via treating polyDMAEMA-grafted columns with
      propylbromide. The polymer grafting degrees varied between 34 and 110%. The
      polycation-grafted monolithic columns are able to capture plasmid DNA directly
      from alkaline lysate of Escherichia coli cells. Due to the large pore size in
      macroporous monoliths the particulate material present in non-clarified feeds did
      not block the columns. The captured plasmid DNA was eluted with 1M NaCl as
      particulate-free preparation with significantly reduced content of protein and
      RNA as compared to the applied lysate.

PMID- 16406157
TI  - High-level expression, purification and pro-apoptosis activity of HIV-TAT
      survivin (T34A) mutant to cancer cells in vitro.
AB  - Survivin, a novel member of the IAP family, was observed to express in the most
      common human cancers. Anti-cancer therapy targeting survivin had drawn
      considerable attention. This study focused on high-level expression of
      recombinant protein TAT-survivin (T34A) mutant in E. coli, purification and
      bioactivity of pro-apoptosis to various cell lines in vitro. The cDNA encoding
      survivin was cloned by RT-PCR from breast cancer cell lines B-cap37. After PCR
      site-directed mutagenesis and construction of expression vector pRSET-B-TAT
      survivin (T34A), targeted TAT-survivin (T34A) protein was expressed highly in E.
      coli BL21 (DE3) by 0.5mM IPTG induction and its yield could reach 650 mg/l in
      fermentation culture. The fusion protein in a form of inclusion body was then
      solubilized, refolded and purified to a purity of 98% by cation exchange
      chromatography and size-exclusion chromatography. Four hundred and eighty
      milligrams protein of interest was obtained in per liter fermentation culture.
      This showed that the efficient procedures of large-scale expression and
      purification were successful for the mass production of the recombinant protein.
      Pro-apoptosis effects of target protein on four cancer cell lines and one normal
      cell line from human were confirmed by the change of morphology, and pro
      apoptosis activity was evaluated by MTT, fluorescent staining of nuclei and flow
      cytometry assay. Results indicated that B-cap37 and SW1990 were very sensitive to
      TAT-survivin (T34A) protein. This finding revealed the recombinant protein was
      promising as an anti-cancer drug.

PMID- 16406158
TI  - Comparative analysis of the outdoor culture of Haematococcus pluvialis in tubular
      and bubble column photobioreactors.
AB  - The present paper makes a comparative analysis of the outdoor culture of H.
      pluvialis in a tubular photobioreactor and a bubble column. Both reactors had the
      same volume and were operated in the same way, thus allowing the influence of the
      reactor design to be analyzed. Due to the large changes in cell morphology and
      biochemical composition of H. pluvialis during outdoor culture, a new, faster
      methodology has been developed for their evaluation. Characterisation of the
      cultures is carried out on a macroscopic scale using a colorimetric method that
      allows the simultaneous determination of biomass concentration, and the
      chlorophyll, carotenoid and astaxanthin content of the biomass. On the
      microscopic scale, a method was developed based on the computer analysis of
      digital microscopic images. This method allows the quantification of cell
      population, average cell size and population homogeneity. The accuracy of the
      methods was verified during the operation of outdoor photobioreactors on a pilot
      plant scale. Data from the reactors showed tubular reactors to be more suitable
      for the production of H. pluvialis biomass and/or astaxanthin, due to their
      higher light availability. In the tubular photobioreactor biomass concentrations
      of 7.0 g/L (d.wt.) were reached after 16 days, with an overall biomass
      productivity of 0.41 g/L day. In the bubble column photobioreactor, on the other
      hand, the maximum biomass concentration reached was 1.4 g/L, with an overall
      biomass productivity of 0.06 g/L day. The maximum daily biomass productivity,
      0.55 g/L day, was reached in the tubular photobioreactor for an average
      irradiance inside the culture of 130 microE/m2s. In addition, the carotenoid
      content of biomass from tubular photobioreactor increased up to 2.0%d.wt.,
      whereas that of the biomass from the bubble column remained roughly constant at
      values of 0.5%d.wt. It should be noted that in the tubular photobioreactor under
      conditions of nitrate saturation, there was an accumulation of carotenoids due to
      the high irradiance in this reactor, their content in the biomass increasing from
      0.5 to 1.0%d.wt. However, carotenoid accumulation mainly took place when nitrate
      concentration in the medium was below 5.0mM, conditions which were only observed
      in the tubular photobioreactor. A similar behaviour was observed for astaxanthin,
      with maximum values of 1.1 and 0.2%d.wt. measured in the tubular and bubble
      column photobioreactors, respectively. From these data astaxanthin productivities
      of 4.4 and 0.12 mg/L day were calculated for the tubular and the bubble column
      photobioreactors. Accumulation of carotenoids was also accompanied by an increase
      in cell size from 20 to 35 microm, which was only observed in the tubular
      photobioreactors. Thus it may be concluded that the methodology developed in the
      present study allows the monitoring of H. pluvialis cultures characterized by
      fast variations of cell morphology and biochemical composition, especially in
      outdoor conditions, and that tubular photobioreactors are preferable to bubble
      columns for the production of biomass and/or astaxanthin.

PMID- 16406159
TI  - Emerging Corynebacterium glutamicum systems biology.
AB  - Corynebacterium glutamicum is widely used for the biotechnological production of
      amino acids. Amino acid producing strains have been improved classically by
      mutagenesis and screening as well as in a rational manner using recombinant DNA
      technology. Metabolic flux analysis may be viewed as the first systems approach
      to C. glutamicum physiology since it combines isotope labeling data with
      metabolic network models of the biosynthetic and central metabolic pathways.
      However, only the complete genome sequence of C. glutamicum and post-genomics
      methods such as transcriptomics and proteomics have allowed characterizing
      metabolic and regulatory properties of this bacterium on a truly global level.
      Besides transcriptomics and proteomics, metabolomics and modeling approaches have
      now been established. Systems biology, which uses systematic genomic, proteomic
      and metabolomic technologies with the final aim of constructing comprehensive and
      predictive models of complex biological systems, is emerging for C. glutamicum.
      We will present current developments that advanced our insight into fundamental
      biology of C. glutamicum and that in the future will enable novel
      biotechnological applications for the improvement of amino acid production.

PMID- 16406160
TI  - Assembly of bacteriophage Qbeta virus-like particles in yeast Saccharomyces
      cerevisiae and Pichia pastoris.
AB  - Recombinant bacteriophage Qbeta coat protein (CP), which has been proposed as a
      promising carrier of foreign epitopes via their incorporation either by gene
      engineering techniques or by chemical coupling, efficiently self-assembles into
      virus-like particles (VLPs) when expressed in Escherichia coli. Here, we
      demonstrate expression and self-assembly of Qbeta CP in yeast Saccharomyces
      cerevisiae and Pichia pastoris. Production reached 3-4 mg/1g of wet cells for S.
      cerevisiae and 4-6 mg for P. pastoris, which was about 15-20% and 20-30% of the
      E. coli expression level, respectively. Qbeta VLPs were easily purified by size
      exclusion chromatography in both cases and contained nucleic acid, shown by
      native agarose gel electrophoresis. The obtained particles were highly
      immunogenic in mice and the resulting sera recognized both E. coli- and yeast
      derived Qbeta VLPs equally well.

PMID- 16406161
TI  - [Sirolimus-associated interstitial pneumonitis in a renal transplant patient].
AB  - INTRODUCTION: Sirolimus is a new immunosuppressive drug used in organ
      transplantation, particularly in renal transplantation. In the future, it could
      replace calcineurin inhibitors such as cyclosporine. It is currently associated
      with side effects, such as thrombocytopenia and hyperlipidemia. Several
      interstitial pneumonitis associated with sirolimus has been previously described
      in renal transplant recipients associated with marked general symptoms. EXEGESIS:
      We report on a 65-year-old renal recipient presenting with a non typical case of
      sirolimus interstitial pneumonitis. He presented with fever and marked general
      symptoms for several months. CT scan showed a unilateral interstitial
      pneumonitis. After infectious, inflammatory and tumoral diseases were ruled out,
      sirolimus associated interstitial pneumonitis was evoked. The patient improved
      quickly after discontinuation of sirolimus. CONCLUSION: It is important to evoke,
      after eliminating other aetiologies, sirolimus induced pneumonitis in face of an
      organ transplant recipient presenting with marked general symptoms even if the
      pulmonary symptoms are not predominant.

PMID- 16406162
TI  - [A rare cause of sub-occlusive syndrome].

PMID- 16406163
TI  - [Burkitt's lymphoma in a patient with systemic lupus erythematosus treated with
      immunosuppressive drugs. A case report].
AB  - INTRODUCTION: Neoplasia and lymphoproliferative disorders are sometimes reported
      in patients with systemic lupus erythematosus (SLE). However, the
      pathophysiological link between lymphoma and SLE is still a matter of debate. We
      report a new case of Burkitt's lymphoma occurring in a patient treated with
      immunosuppressive drugs for SLE. CASE REPORT: A 38-year-old woman with SLE
      treated for 10 years with immunosuppressive drugs was admitted for the rapid
      onset of multiple neuritis with cranial nerves palsy, without extra-neurological
      involvement. The cerebrospinal fluid was normal. A bone marrow biopsy revealed
      Burkitt's lymphoma. CONCLUSION: This is the third case reported of Burkitt's
      lymphoma occurring in SLE. Here we discuss the data of the literature and the
      possible pathophysiological links between Burkitt's lymphoma and SLE.

PMID- 16406165
TI  - Mercury accumulation in surface sediments of salt marshes of the Bay of Fundy.
AB  - Mercury contamination in Canada's Bay of Fundy is a priority concern because of
      elevated levels observed in fish, birds and wildlife. Salt marshes constitute an
      important part of the Bay's coastline and are potential stores of mercury for the
      region. We measured the amount of mercury accumulated over a 5-yr period from
      1997 to 2002 in surface sediments of seven salt marshes along the New Brunswick
      coast of the Bay. The seven study sites extended from outer to inner Bay,
      spanning a gradient in tidal range (6-12 m) and sediment characteristics such as
      %LOI (4-29%) and sediment deposition rate (0.27-1.76 cm yr(-1)). In each study
      site, mercury was measured in low and high marsh areas. Sediment mercury
      concentrations ranged from 7 to 79 ng g(-1) and loading rates ranged from 0.1 to
      1.1 mg m(-2). Total estimated 5-yr storage of mercury in salt marsh sediments of
      the Bay is 854+/-465 kg. We also compared sediment mercury loading to atmospheric
      inputs measured at a deposition monitoring station operating in New Brunswick
      from 1997 to 2002 and found that direct atmospheric deposition appears to be a
      minor input of mercury to these sediments. We are unaware of documentation of
      mercury loading in salt marshes on a bay-wide scale and over a constrained (5-yr)
      time period elsewhere.

PMID- 16406164
TI  - Detrital control on the release of dissolved organic nitrogen (DON) and dissolved
      inorganic nitrogen (DIN) from the forest floor under chronic N deposition.
AB  - The role of detrital quantity and quality in forest floor N leaching was
      investigated in a litter manipulation experiment at a deciduous forest under
      chronic N deposition. Dissolved inorganic nitrogen (DIN) comprised the bulk of
      nitrogen leaching from the control except a short period following autumn
      litterfall. The dominance of DIN was strengthened by litter exclusion, whereas
      the addition of glucose or fresh litter led to a small increase in dissolved
      organic nitrogen (DON) and either a temporary or gradual reduction in NO(3)(-)
      release, respectively. Changes in soluble organic C and microbial C in the forest
      floor implied that increased availability of C sources might have enhanced
      microbial immobilization of DIN, either temporarily following glucose application
      or over the longer term following litter addition. The results suggest that
      detrital quantity and quality can play a crucial role in determining the balance
      between DIN and DON in N-enriched forest soils.

PMID- 16406166
TI  - The efficiency of interference of Potato virus X infection depends on the target
      gene.
AB  - RNA silencing is a natural defense response against viral infection. This
      phenomenon has been used to interfere with viral infections by exploiting
      fragments of viral genomes as sources of RNA silencing. Agrobacterium-mediated
      transient expression of a hairpin RNA derived from the TGBp1 gene of Potato virus
      X (PVX) induced RNA silencing of the TGBp1 gene and resulted in interference of
      PVX infection. The interference was induced in the infiltrated leaves but not in
      the upper non-infiltrated leaves. Transient expression of a CP hairpin RNA also
      induced interference of PVX. The TGBp1 hairpin RNA showed more efficient
      interference of PVX infection than the CP hairpin RNA.

PMID- 16406167
TI  - Characterization of Epstein-Barr virus Type I variants based on linked
      polymorphism among EBNA3A, -3B, and -3C genes.
AB  - Latent Epstein-Barr virus (EBV) nuclear antigens (EBNA)-3A, -3B, and -3C are
      involved in transcription regulation of both viral and cellular genes. In the
      present study, we chose functionally important regions within EBNA3A, -3B, and 
      3C genes with putative tumorigenic potential to investigate natural sequence
      variations among EBV Type I strains circulating in Europe. Based on the
      identification of linked EBNA3A, -3B, and -3C sequence patterns, we defined five
      EBNA3 variants in addition to the B95.8 prototype sequence. Phylogenetic analysis
      revealed that EBNA3 variant 5, the most diverged from the B95.8 sequence, showed
      an evolutionary history of intertypic recombination events occurring upstream and
      downstream of the C-terminus of EBNA3A. The frequency of occurrence of the five
      newly defined EBNA3 variants was similar for strains causing EBV primary
      infection or reactivation and was also similar within two of the European areas
      investigated. In addition, preferential linkages of certain EBNA3 variants to
      distinct latent membrane protein 1 (LMP1) groups were found to exist. Thus, a
      combination of more than one polymorphic site in the EBV genome might be involved
      in determining disease characteristics.

PMID- 16406169
TI  - Negative impact of porcine reproductive and respiratory syndrome virus infection
      on the efficacy of classical swine fever vaccine.
AB  - Recent findings suggest that porcine reproductive and respiratory syndrome virus
      (PRRSV) possesses immunomodulatory properties. To investigate the effect of PRRSV
      infection on classical swine fever (CSF) vaccine efficacy, 17-day-old pigs were
      divided into five groups. The experimental group was infected with a Thai PRRSV
      (US genotype) a week before CSF vaccination and challenged with a virulent CSF
      virus (CSFV) 3 weeks following vaccination. The control groups received no PRRSV
      infection, no CSF vaccination, no CSF challenge, or in combination were included.
      The results demonstrated that PRRSV infection significantly inhibited host immune
      response that resulted in vaccination failure in the subsequent CSFV exposure.
      Following CSF challenge, the PRRSV-infected, vaccinated pigs exhibited clinical,
      virological and pathological features resembled to those of the non-vaccinated
      groups. The findings indicated that CSF immunization during an acute phase of
      PRRSV infection could result in vaccination failure.

PMID- 16406168
TI  - Vaccination with DNA encoding cysteine proteinase confers protective immune
      response to rats infected with Clonorchis sinensis.
AB  - Cysteine proteinases of C. sinensis are important virulence factors that induce
      pathological changes associated with larval migration and localized biliary
      epithelial destruction. This study investigated the immunogenicity and protective
      efficacy of a DNA vaccine encoding Clonorchis sinensis cysteine proteinase
      (CsCP). The CsCP cDNA sequence displays significant homology to the mammalian or
      trematode cathepsin L. Plasmid DNA carrying the CsCP gene (pcDNA3.1-CsCP) was
      injected into Sprague-Dawley (SD) rats intradermally. Animals injected with
      pcDNA3.1-CsCP developed CsCP-specific antibodies, which exhibited an IgG2a
      dominance in sera. In addition, the DNA vaccine elicited the production of IFN
      gamma, but not IL-4 in splenocytes, suggesting the induction of a typical Th-1
      dominated immune response in rats. The pcDNA3.1-CsCP induced a significant level
      of protection (31.5%, p<0.05) in SD rats challenged with C. sinensis
      metacercariae. These results indicate that pcDNA3.1-CsCP induces both humoral and
      cellular immune responses. The CsCP gene may be a good candidate for use in
      future studies of vaccination against clonorchiasis.

PMID- 16406170
TI  - Transmissibility, infectivity and immunogenicity of a live human parainfluenza
      type 3 virus vaccine (HPIV3cp45) among susceptible infants and toddlers.
AB  - BACKGROUND: This study examined the transmissibility between young children of an
      intranasally administered live attenuated human parainfluenza virus type 3
      (HPIV3)-cp45 vaccine candidate. METHODS: Eighty subjects were enrolled in
      playgroups among whom there was at least one infected vaccinee in close contact
      with a seronegative placebo recipient over 21 days without a confounding
      infection with wtHPIV3. Following vaccination viral cultures were obtained on
      nine occasions to detect shedding and transmission of HPIV3cp45. Serum antibody
      titers were measured before and 7 weeks after vaccination. RESULTS: No child
      fulfilled the criteria for transmission of HPIV3cp45 giving a risk of
      transmission of 0.04 (95% CI 0.01-0.19), hence establishing that HPIV3cp45 is
      less infectious than wtHPIV3 and risk of transmission is not a limitation to
      further clinical development of this vaccine candidate.

PMID- 16406171
TI  - Reactogenicity and immunogenicity of an inactivated influenza vaccine
      administered by intramuscular or subcutaneous injection in elderly adults.
AB  - In many countries there is no clear recommendation regarding the preferred route
      of administration of inactivated influenza vaccines. In a randomised, observer
      blind study of 720 elderly subjects, a split, trivalent influenza vaccine was
      significantly more immunogenic for both A strains (H3N2 and H1N1, p = 0.0016 and
      0.003, respectively) when given intramuscularly compared to subcutaneously. This
      difference was due entirely to a gender effect, with females in the intramuscular
      (IM) group having a significantly greater serological response than females in
      the subcutaneous (SC) group for both of these strains. Similar results were seen
      with local adverse effects. These data suggest that vaccination practices that
      ensure intramuscular injection are required for optimal administration of
      influenza vaccines in the elderly.

PMID- 16406172
TI  - Immunization of Rhesus monkeys with the conjugate vaccine IGN402 induces an IgG
      immune response against carbohydrate and protein antigens, and cancer cells.
AB  - Tumor-associated antigens resulting from aberrant glycosylation, such as the
      SialylTn carbohydrate antigen, are over-expressed on cancer cells and provide
      potential targets for cancer vaccination. However, as T-cell-independent antigens
      carbohydrates are poorly immunogenic, and fail to induce memory. In order to
      increase the immunogenicity we have coupled the SialylTn carbohydrate antigen to
      a highly immunogenic carrier molecule, the murine monoclonal antibody mAb17-1A.
      An immunogenic formulation of the SialylTn-mAb17-1A conjugate on alhydrogel,
      IGN402, with or without additional adjuvants was tested in Rhesus monkeys for
      tolerability and immunogenicity. A significant antibody response against mAb17-1A
      antibody was found. Importantly, also a specific immune response against SialylTn
      carbohydrate and binding to tumor cells was induced. Immunization in the presence
      of additional adjuvants, such as QS-21, strongly enhanced the immune response
      against the carbohydrate antigen, and resulted in induction of SialylTn-specific
      IgG antibodies. Noteworthy, also an induced temporary release of cytokines
      including IFNgamma and IL-2, indicative for T-cell activation, was measured. The
      data indicate that carrier-induced T-cell help together with strong adjuvant is
      sufficient for carbohydrate specific class switch induction.

PMID- 16406173
TI  - The cellular immune response in the tracheal mucosa to Mycoplasma gallisepticum
      in vaccinated and unvaccinated chickens in the acute and chronic stages of
      disease.
AB  - Mycoplasma gallisepticum causes a lymphoproliferative response in the tracheal
      mucosa of infected birds. The studies reported here aimed to determine, using
      immunohistochemical and immunofluorescent staining, which lymphocyte subsets were
      infiltrating the mucosa during the acute and chronic phases of disease and to
      determine whether these subsets differed in birds that had been vaccinated with
      strain ts-11. In vaccinates there was no detectable infiltration of T or B
      lymphocytes between 1 and 6 weeks after infection with a virulent strain.
      Unvaccinated birds had an initial influx of CD8+TCR- lymphocytes at 1 week, with
      the numbers decreasing over the next 5 weeks. CD8+TCR+ cells increased over the 6
      weeks. The proportion of CD4+TCRalphabeta2+ cells also increased, whilst there
      was an increase in CD4+TCRalphabeta1+ cells at 3 weeks and then a decrease by 6
      weeks. B lymphocytes were not detected until 3 weeks after infection, and their
      appearance coincided with a decrease in the concentration of mycoplasma DNA
      detectable in the trachea. The formation of clusters of CD8+TCR- lymphocytes was
      a prominent feature of the early response, while at 3 and 6 weeks after infection
      clusters of B cells became prominent, although in some cases they surrounded a
      cluster of CD8+ cells. These observations suggest a primary role for local
      antibody mediated responses in controlling M. gallisepticum infection, but also
      show that there are probably significant natural killer and cytotoxic T cell
      responses to infection, although the efficacy of these in controlling infection
      was not able to be determined.

PMID- 16406174
TI  - How far can the antigen content of tissue culture rabies vaccine be reduced
      safely?

PMID- 16406175
TI  - Ventrogluteal area--a suitable site for intramuscular vaccination of infants and
      toddlers.
AB  - Buttock vaccination has lower reactogenicity and similar immunogenicity to the
      two other recommended paediatric vaccination sites (deltoid and anterolateral
      thigh). Safety concerns about buttock injection derived from injections with
      neurotoxic agents, like penicillin but not vaccines, have become entrenched.
      However, the ventrogluteal area is considered safe for intramuscular injection.
      This study outlines the development of the ventrogluteal area as a suitable site
      for intramuscular vaccination of infants and toddlers. Measurement was made in
      642 children, aged 2-18 months and age-specific templates were prepared. These
      were used in an untrasonographic study of 57 children aged 2-18 months to
      determine the tissue composition of the ventrogluteal area compared with the
      recommended anterolateral thigh vaccination site. The ventrogluteal area was
      found to be clearly defined by the template and suitable for intramuscular
      injection. Subsequent vaccination studies with the area showed that it was:

PMID- 16406176
TI  - Humoral and cellular immune responses to influenza vaccine in patients with
      advanced cirrhosis.
AB  - Influenza vaccine has been shown to successfully reduce influenza- and pneumonia
      associated hospitalizations and deaths. Yet in liver cirrhosis, influenza
      vaccines have received little attention in determining the potential benefits.
      Thus, we undertook this study to evaluate the humoral and cellular immune
      responses to vaccination against influenza in patients with advanced cirrhosis.
      We measured interferon (IFN)-gamma secretion response and hemagglutinin
      inhibition (HI) of antibody titer from pre- and post-vaccination blood samples in
      80 cirrhotic patients (Child-Pugh class B or C) and 80 healthy, age-matched
      subjects. Although the patients with advanced cirrhosis showed similar humoral
      immune response against influenza vaccination compared to the healthy controls,
      cell-mediated immunity showed different results according to the remnant liver
      function.

PMID- 16406177
TI  - Protective effects of guarana (Paullinia cupana Mart. var. Sorbilis) against DEN
      induced DNA damage on mouse liver.
AB  - Guarana (Paullinia cupana Mart. var. Sorbilis) is a plant originally from Brazil,
      which is rich in tannins. Some tannins are known to present protective effects
      against DNA damage. This study was performed to investigate the anti
      genotoxic/cytotoxic properties of guarana in hepatocytes of mice injected with N
      nitrosodiethylamine (DEN). The protective effect of guarana was evaluated both by
      comet assay and DNA smear fragmentation technique in two month-old female BALB/c
      mice. These were treated previously with 2.0 mg/g bw of guarana for 16 days and
      then injected with DEN (160 microg/g body weight) to induce DNA damage. The DEN
      only treated group presented higher comet image length than the guarana plus DEN
      and untreated groups (116.06+/-5.0 microm, 104.09+/-3.3 microm and 93.28+/-14.4
      microm, respectively; p<0.01). Guarana treatment presented a 52.54% reduction in
      comet image length when animals were exposed to DEN (p<0.05). DNA samples from
      the guarana plus DEN group clearly showed less EtBr fluorescence intensity when
      compared to the DEN-only group, reinforcing the comet assay data. These results
      show, for the first time, that guarana has a protective effect against DEN
      induced DNA damage in mouse liver.

PMID- 16406178
TI  - Low-grade myofibroblastic sarcoma of the piriform fossa: a case report with a
      literature review of a tumour with a predilection for the head and neck.
AB  - A low-grade myofibroblastic sarcoma was removed from the pyriform fossa of a 44
      year-old man. It recurred 4 years later and was removed radically through an
      incision in the neck. There has been no further recurrence after 11 years.

PMID- 16406179
TI  - Treatment of post-traumatic open bite by radiofrequency.
AB  - An 18-year-old man with a fracture of the mandibular symphysis and both condylar
      heads was treated by open reduction of the fractured symphysis and closed
      reduction of the fractures of the condylar heads. As the open-bite was not
      resolved by the operation, elastic traction was applied for three weeks, but
      there was no improvement. Finally, we gave radiofrequency treatment to the
      anterior bellies of the digastric muscle, after which the open-bite disappeared
      and at the follow-up examinations there was no recurrence.

PMID- 16406180
TI  - Antimicrobial resistance of Clostridium difficile isolates in a tertiary medical
      center, Israel.
AB  - The antimicrobial susceptibilities of 49 Clostridium difficile isolates obtained
      from patients with C. difficile-associated diarrhea to metronidazole, vancomycin,
      rifampicin, fusidic acid, doxycycline, and linezolid were determined by the disc
      diffusion and Etest (Biodisk, Solna, Sweden). Random amplification of polymorphic
      DNA-PCR amplification assay was performed for studying clonality of isolates.
      Resistance to metronidazole was found in 2% (1/49 isolates; MIC > or = 256
      microg/mL) of isolates and resistance to linezolid in 2% (1/49 isolates; MIC = 24
      microg/mL). One isolate showed combined resistance to fusidic acid (by disc
      diffusion test) and rifampicin (MIC > or = 32 microg/mL). All isolates were
      sensitive to doxycycline and vancomycin. Molecular typing revealed an absence of
      clonality among the resistant isolates, whereas the sensitive isolates were
      monoclonal. Resistance of C. difficile to metronidazole and other antimicrobials
      including linezolid exists in our institution. This finding should promote
      exploration of this problem in Israel and clarify the impact of resistance on
      outcome.

PMID- 16406181
TI  - Emergence of multidrug-resistant Corynebacterium striatum as a nosocomial
      pathogen in long-term hospitalized patients with underlying diseases.
AB  - During a 53-month period (March 1994 to August 1998), 48 Corynebacterium striatum
      isolates recovered from clinical specimens were characterized. The organisms were
      identified by both phenotypic characteristics and 16S rRNA gene sequence
      analysis. Thirty-six (75%) were isolated from sputum/bronchial aspirates, 10
      (21%) from wound exudates/pus, 1 (2%) from vaginal discharge, and 1 (2%) from an
      otorrheic specimen. All 48 patients had been hospitalized for treatment of an
      underlying disease and had received antibiotics previously. The C. striatum
      isolates were considered pathogenic based on their abundance within
      polymorphonuclear neutrophils and their dominant growth in culture. Sensitivities
      of isolates to 11 antibiotics were determined by broth microdilution. MIC90
      values of the isolates were 1 microg/mL for vancomycin, 16 microg/mL for
      penicillin and ampicillin, 32 microg/mL for minocycline, and > or = 32 microg/mL
      for cephalosporins, imipenem, ofloxacin, and macrolides. Restriction fragment
      length polymorphism analysis with pulsed-field gel electrophoresis was used to
      determine the clonal identity. The pulse-field gel electrophoresis profiles
      revealed 14 distinct patterns with 20 subtypes. The isolates for the nosocomial
      outbreaks of C. striatum included 3 types (A, D, and E) with 4 subtypes (A1, A2,
      D2, and E). All 4 genotypes had broad-spectrum resistance to antimicrobial
      agents. Furthermore, type E strain isolated from 3 patients in the same ward was
      sensitive only to vancomycin. We conclude that C. striatum should be considered
      an emerging multidrug-resistant nosocomial pathogen in patients hospitalized for
      a prolonged period and/or in immunocompromised patients with such underlying
      conditions as cerebrovascular disease, pulmonary disease, diabetes, or
      malignancy.

PMID- 16406182
TI  - Reliability of rapid urinary test for antibody to Helicobacter pylori in adult
      patients with proteinuria.
AB  - A urinary test for detecting the anti-H. pylori antibody using
      immunochromatography (RAPIRAN) is considered suitable for the screening purpose.
      However, this may yield spurious results in the presence of proteinuria. The
      present study was conducted to evaluate the diagnostic performance of RAPIRAN in
      patients with proteinuria. Urine and serum samples of adult inpatients with
      proteinuria were used for analyses. The diagnosis of H. pylori infection was made
      based on the seropositivity of anti-H. pylori antibody using 2 different serum
      tests. Fifty-one subjects were eligible for analyses. The serum tests showed
      negative and positive in 25 and 26 patients, respectively. Two of 25 seropositive
      patients had a negative result in RAPIRAN, and 1 provided invalid data. All of
      seronegative patients showed negative in RAPIRAN. The overall accuracy was 95.0%.
      The present study showed that RAPIRAN has diagnostic quality enough to use
      clinically also in patients with proteinuria.

PMID- 16406183
TI  - Comparison of quantitative competitive polymerase chain reaction-enzyme-linked
      immunosorbent assay with LightCycler-based polymerase chain reaction for
      measuring cytomegalovirus DNA in patients after hematopoietic stem cell
      transplantation.
AB  - Development of highly sensitive quantitative assays for cytomegalovirus (CMV) DNA
      detection is crucial for identification of immunodeficient patients at high risk
      of CMV disease. We designed 2 internally controlled competitive quantitative
      assays, enzyme-linked immunosorbent assay (ELISA)-based and real-time polymerase
      chain reaction (PCR) tests, using amplification of the same segment of the CMV
      genome. The aim of this study was to compare sensitivity, specificity, and
      laboratory performance characteristics of these assays. In both assays, a 159-bp
      segment of UL83 gene was amplified. External and internal controls were
      constructed by cloning the amplification product and heterogenous DNA segment
      flanked by target sequences for CMV-derived primers into bacterial plasmids,
      respectively. Real-time PCR was performed on LightCycler (Roche Diagnostics,
      Mannheim, Germany), and amplicons were detected using fluorescence resonance
      energy transfer probes. Alternatively, PCR products were labeled by digoxigenin,
      hybridized to immobilized probes, and detected by ELISA. The assays were tested
      on genomic DNA isolated from laboratory strains of CMV, QCMD control panel, and
      CMV DNA-positive peripheral blood DNA samples from hematopoietic stem cell
      transplant recipients, previously characterized by pp65 antigenemia and
      qualitative nested PCR. Real-time and ELISA-based PCR assays showed a linear
      course of 1-10(8) and 10-10(5) copies of CMV DNA per reaction, respectively. When
      compared with ELISA-based PCR, real-time PCR showed superiority in inter- and
      intra-assay reproducibility. Both assays were highly specific in detecting CMV
      DNA. No difference in amplification efficiency of internal or external standards
      and wild-type CMV DNA was found. The assays exhibited 83% concordance in CMV DNA
      detection from clinical samples, all discrepant samples having low CMV DNA copy
      numbers. There was a good correlation between viral DNA loads measured by the 2
      assays. Statistically significant correlation was observed between the numbers of
      CMV DNA copies and pp65-positive leukocytes in the samples tested. Both variants
      of competitive PCR are adequately sensitive to be used for CMV DNA quantitation
      in clinical samples. LightCycler PCR, having superior performance characteristics
      and being less time-consuming, seems to be more suitable for routine diagnosis.

PMID- 16406184
TI  - Detection of Mycobacterium tuberculosis DNA in respiratory and nonrespiratory
      specimens by the Amplicor MTB PCR.
AB  - To evaluate the diagnostic performance of a commercially available Mycobacterium
      tuberculosis PCR assay (Amplicor MTB-ROCHE), 2296 respiratory and nonrespiratory
      specimens from 2296 patients with suspected tuberculosis (TB) were collected
      prospectively in an 8-year period. Clinical data for each patient were
      abstracted, and all samples were examined blindly by direct microscopy, culture,
      and PCR. M. tuberculosis DNA was detected in 93 of 113 culture-positive samples
      and in 29 of 38 samples from patients with probable TB. The lowest sensitivity
      was observed in pleural fluid and abscess aspirates. The sensitivity,
      specificity, and positive predictive value of the assay were 97.2%, 100%, and
      100% for smear-positive specimens and 75.3%, 97.0%, and 47.5% for smear-negative
      specimens, respectively. The PCR cost per additional correct clinical decision
      was Euro 2826 but would have declined to Euro 308 if the test was applied only to
      smear-positive specimens. The overall performance of Amplicor MTB test was
      excellent for smear-positive, but suboptimal for smear-negative specimens.

PMID- 16406185
TI  - Dissemination of Proteus mirabilis isolates harboring CTX-M-14 and CTX-M-3 beta
      lactamases at 2 hospitals in Taiwan.
AB  - From February to June 2003, 111 clinical isolates of Proteus mirabilis were
      mainly isolated from patients with respiratory or urinary tract infections
      hospitalized at 3 district hospitals (A, B, C) in central Taiwan. Among them, 34
      (30.6%) strains, isolated within 2 hospitals (A and B), exhibited
      nonsusceptibility to cefotaxime with significant reduction of MIC (> or = 3 log2
      dilution) by the effect of clavulanic acid, which confirmed the phenotype of
      extended-spectrum beta-lactamases (ESBLs). These ESBL producers were coresistant
      to gentamicin, isepamicin, and amikacin, but remained susceptible to ceftazidime
      (MIC, < or = 0.5 microg/mL) and meropenem (MIC, <0.5 microg/mL). By isoelectric
      focusing analysis, polymerase chain reaction, and nucleotide sequencing, we
      detected the presence of CTX-M-14 in 33 strains and CTX-M-3 in 6 strains (5
      strains harboring both CTX-M-14 and CTX-M-3 enzymes). These beta-lactamase genes
      can be successfully transferred by the conjugative plasmid. Molecular
      epidemiology of the 34 ESBL-producing P. mirabilis strains by pulsed-field gel
      electrophoresis using SfiI restriction enzyme revealed 9 different genotypes,
      suggesting epidemic clones with intra- and interhospital spread. In conclusion,
      the broadly extended clonal spreading of CTX-M-type P. mirabilis was first
      discovered at the district hospitals in Taiwan.

PMID- 16406186
TI  - Simultaneous coinfection by multiple strains during Burkholderia cepacia complex
      infection in cystic fibrosis.
AB  - Much remains unknown about the natural history of respiratory tract infection by
      Burkholderia cepacia complex (Bcc) in persons with cystic fibrosis (CF).
      Specifically, it is not clear whether infected CF patients typically harbor a
      single Bcc strain or multiple strains that may be phenotypically
      indistinguishable. We genotyped 912 Bcc isolates recovered from CF sputum culture
      from in excess of 100 patients to demonstrate that chronic infection generally
      involves a single strain. Transient coinfection with more than 1 strain occurs
      infrequently and may be more common early in the course of Bcc infection.

PMID- 16406187
TI  - In vitro activity of beta-lactam and non-beta-lactam antibiotics in extended
      spectrum beta-lactamase-producing clinical isolates of Escherichia coli.
AB  - The activity of different beta-lactam and non-beta-lactam antibiotics was
      assessed against extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL
      producing clinical isolates of Escherichia coli. A phenotypic study to discover
      the presence of ESBLs in 399 clinical isolates of E. coli was made by the disk
      diffusion method following the Clinical and Laboratory Standards Institute
      (formely NCCLS, 2004) guidelines. The activity of different antibiotics was
      subsequently studied using the automated VITEK 2 system (bioMerieux, Marcy
      l'Etoile, France). One hundred fifteen isolates proved to be ESBL-producing and
      284 non-ESBL-producing. Among the former, percentage susceptibilities to the
      antibiotics assayed were meropenem and amikacin, 100%; piperacillin/tazobactam,
      97.4%; cefepime, 94.8%; amoxicillin/clavulanic acid, 84.3%; tobramycin, 84.3%;
      gentamicin, 83.5%; cefoxitin, 83.5%; nitrofurantoin, 71.3%; cotrimoxazole, 46.1%;
      norfloxacin, 29.6%; ciprofloxacin, 27%; and ofloxacin, 26.1%.

PMID- 16406188
TI  - Modelling the effects of road traffic safety measures.
AB  - A model is presented for assessing the effects of traffic safety measures, based
      on a breakdown of the process in underlying components of traffic safety (risk
      and consequence), and five (speed and conflict related) variables that influence
      these components, and are influenced by traffic safety measures. The
      relationships between measures, variables and components are modelled as
      coefficients. The focus is on probabilities rather than historical statistics,
      although in practice statistics may be needed to find values for the
      coefficients. The model may in general contribute to improve insight in the
      mechanisms between traffic safety measures and their safety effects. More
      specifically it allows comparative analysis of different types of measures by
      defining an effectiveness index, based on the coefficients. This index can be
      used to estimate absolute effects of advanced driver assistance systems (ADAS)
      related measures from absolute effects of substitutional (in terms of safety
      effects) infrastructure measures.

PMID- 16406189
TI  - Persistent impaired glucose tolerance has similar rate of risk factors as for
      diabetes--results of Indian diabetes prevention programme (IDPP).
AB  - OBJECTIVE: To determine the occurrence of persistent impaired glucose tolerance
      (IGT) (two times OGTT positive) and to compare the physical and clinical
      characteristics with subjects having transient IGT or diabetes. RESEARCH DESIGN
      AND METHODS: Nondiabetic subjects aged 35-55 years were screened (n=10,839, M:W
      8667:2172) using 2h capillary blood glucose. IGT was diagnosed in 1332 (12.3%).
      Among them, 1025 (77%) responded for a second OGTT and 531 subjects (51.8%) had
      persistent IGT. Biochemical, demographic and anthropometric characteristics were
      compared among the normal (NGT, 30.1%), IGT and diabetic subjects (DM, 18%) at
      second GTT. RESULTS: All had similar age. BMI, waist circumference and body fat
      percentage were lower in NGT than in IGT and diabetes. IGT and diabetes had
      similar characteristics. Family history of diabetes was the highest in persistent
      IGT. CONCLUSION: Among the screened subjects, 1 in 20 had persistent IGT. Subject
      with persistent IGT had higher rates of risk factors for diabetes, such as high
      BMI, waist circumference and body fat percentage.

PMID- 16406190
TI  - Comparative efficacy of glimepiride and/or metformin with insulin in type 2
      diabetes.
AB  - BACKGROUND AND AIMS: The data regarding comparison of efficacy of metformin with
      glimepiride, newest Sulfonylurea, or with the use of both drugs in combination
      with insulin is rare in the literature. Therefore, we assessed the daily insulin
      dose, hypoglycemic events and body weight on achieving desirable glycemic control
      after addition of insulin, to glimepiride 8 mg and/or metformin 2500 mg, in
      subjects with type 2 DM manifesting lapse of glycemic control. METHODS: S.C.
      insulin Novolog Mix [70/30], pre-supper was initiated in 12 subjects on
      metformin, 14 subjects on glimepiride, and 12 subjects receiving both drugs, with
      HbA1C > 7.5% and eight subjects receiving placebo. Insulin dose was increased by
      4 U at weekly interval until fasting blood sugar [FBS] between 6.6 and 8 mM/l was
      attained and then further titrated by 2 U every week to attain and maintain FBS
      between 4.5 and 6.7 mM/l over the next 4 months. The comparisons were conducted
      between these groups for HbA1C, the daily insulin dose, body weight noted at the
      end of this study period as well as the hypoglycemic episodes per patient during
      the last 4 weeks of the study period. RESULTS: HbA1C levels were < 7.0% in all
      subjects at the end of the study. The daily insulin dose (units), total and per
      kg/BW was significantly lower [p < 0.001] with metformin (51 +/- 5, 0.51 +/-
      0.10), glimepiride (40 +/- 4, 0.42 +/- 0.09) as well as with both drugs (23 +/-
      7, 0.21 +/- 0.07) in comparison to placebo (82 +/- 10, 0.82 +/- 0.12). The
      insulin dose was also significantly lower [p < 0.05] in subjects on both drugs
      than subjects receiving them individually. Weight gain was less [p < 0.001] with
      metformin [2.5 +/- 0.74 kg], glimepiride [2.3 +/- 0.7 kg], and both drugs [2.2 +/
      0.61 kg] in comparison to placebo [5.2 +/- 1.4 kg] whereas the hypoglycemic
      episodes were lesser with metformin (3.8 +/- 1.2) and glimepiride (3.3 +/- 0.9)
      and least with both drugs (2.5 +/- 0.6) in comparison to placebo (5.2 +/- 1.0).
      CONCLUSION: Glimepiride and metformin are effective individually in achieving a
      glycemic goal with a less daily insulin dose, weight gain, and hypoglycemic
      episodes in comparison to insulin monotherapy in subjects with type 2 diabetes
      mellitus with further marked reduction in these parameters when used
      concurrently.

PMID- 16406191
TI  - GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic
      ducts.

PMID- 16406192
TI  - Impact of finger posture on mapping from muscle activation to joint torque.
AB  - BACKGROUND: The mapping from muscle activation to joint torque production can be
      difficult to determine for the multi-articular muscles of the fingers. This
      relationship was examined in vivo as a function of posture in the index finger.
      METHODS: Five healthy adults participated in an experiment in which the seven
      muscles of the index finger were sequentially electrically stimulated using
      intramuscular electrodes. Each muscle was stimulated at 12 different finger
      postures consisting of specified flexion of the metacarpophalangeal, proximal
      interphalangeal, and distal interphalangeal joints, while fingertip forces and
      moments were recorded. FINDINGS: Repeated measures analysis of variance revealed
      that joint torques resulting from the stimulation were significantly dependent
      upon finger posture (p < 0.05). The magnitude of the change in joint torque
      across postures was generally greater than 60%. This value is much larger than
      the difference attributable to the increase in active muscle force that occurs at
      longer muscle length, in accordance with the force-length curve (10-20% for the
      estimated length changes). In addition, the relative distribution of the joint
      torques generated by a given muscle activation was dependent upon finger posture
      for the intrinsic muscles and the long finger flexors (p < 0.05); the ratio of
      one joint torque to another varied with posture for these muscles, in some cases
      by more than 50%. INTERPRETATION: Joint torque is a product of both muscle force
      and the corresponding moment arm. As the change in active muscle force was
      limited, these data suggest that substantial changes in muscle moment arms occur
      with posture. Therefore, this postural dependence should be considered when
      constructing biomechanical models of the hand or planning tendon transfers for
      the fingers.

PMID- 16406193
TI  - An efficient and high-throughput approach for experimental validation of novel
      human gene predictions.
AB  - A highly automated RT-PCR-based approach has been established to validate novel
      human gene predictions with no prior experimental evidence of mRNA splicing (ab
      initio predictions). Ab initio gene predictions were selected for high-throughput
      validation using predicted protein classification, sequence similarity to other
      genomes, colocalization with an MPSS tag, or microarray expression. Initial
      microarray prioritization followed by RT-PCR validation was the most efficient
      combination, resulting in approximately 35% of the ab initio predictions being
      validated by RT-PCR. Of the 7252 novel genes that were prioritized and processed,
      796 constituted real transcripts. In addition, high-throughput RACE successfully
      extended the 5' and/or 3' ends of >60% of RT-PCR-validated genes. Reevaluation of
      these transcripts produced 574 novel transcripts using RefSeq as a reference. RT
      PCR sequencing in combination with RACE on ab initio gene predictions could be
      used to define the transcriptome across all species.

PMID- 16406194
TI  - Structures, regulatory regions, and inductive expression patterns of
      antimicrobial peptide genes in the silkworm Bombyx mori.
AB  - Antimicrobial peptides (AMPs) are a group of immune proteins that protect the
      host from infection. In Drosophila, seven groups of inducible AMPs have been
      identified, with activities against fungi and gram-positive and gram-negative
      bacteria. On the basis of the silkworm genome sequence and expressed sequence
      tags, we identified 35 AMP genes, mostly belonging to the cecropin, moricin, and
      gloverin gene families. We predicted the core promoters required for gene
      transcription and the cis-regulatory elements for NF-kappaB/Rel and GATA
      transcription factors. The expression profiles of these genes after an immune
      challenge with lipopolysaccharide were examined by reverse transcription PCR.
      Members of the cecropin B and gloverin A subfamilies were intensely expressed in
      the fat body after induction. In contrast, those of the moricin B subfamily were
      not expressed under the same conditions. Such results suggest that these
      regulatory elements and their positions in the upstream regions play an important
      role in regulating the transcription of these defense genes.

PMID- 16406195
TI  - Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer
      risk and response to platinum-based chemotherapy in non-small cell lung cancer
      (NSCLC) patients.
AB  - PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome
      in patients with resectable non-small cell lung cancer (NSCLC). Here, we
      investigated the impact of this polymorphism on smoking-induced cancer risk and
      clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G
      genotype was determined by polymerase chain reaction (PCR) and restriction
      fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The
      study included 244 NSCLC patients and 187 healthy control subjects. RESULTS:
      Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27%
      squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV
      disease. Median age at diagnosis was 60 years and median survival was 13 months.
      Genotype frequencies of patients and controls both conformed to the Hardy
      Weinberg equilibrium. The GG genotype significantly correlated with a history of
      heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a
      significantly higher cigarette consumption than patients with AA/AG genotypes
      (P=0.007). The GG genotype also significantly correlated with tumor response or
      stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival
      analysis revealed no significant differences among the genotypes. CONCLUSION:
      Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking
      induced lung cancer risk. Further studies are required to explore the underlying
      molecular mechanisms and to test the value of this gene polymorphism as a
      predictor for platinum-sensitivity in NSCLC patients.

PMID- 16406196
TI  - Relapse to alcohol and drug use among individuals diagnosed with co-occurring
      mental health and substance use disorders: a review.
AB  - This paper reviews the literature investigating relapse to alcohol and drug use
      among individuals dually diagnosed with a substance use and a co-occurring mood,
      anxiety, schizophrenia-spectrum, or personality disorder. Prevalence rates for
      each co-occurring set of disorders are discussed, followed by research studies
      that examine predictors of relapse to substance use within these groups. Relevant
      conceptual models well-suited to incorporating relapse as an outcome variable,
      and psychiatric factors both as predictor and outcome variables, are presented.
      Suggestions for future studies are provided. A priority area is developing and
      using consistent and well-articulated definitions of relapse across studies.
      Several diagnostic issues surfaced such as using structured clinical interviews
      to determine diagnosis (preferably following detoxification from alcohol and/or
      drugs), separating individuals with only alcohol use disorders from those with
      alcohol and drug use disorders in analyses, reporting the rates and types of
      overlap in mental health diagnoses, and conducting analyses that include and
      exclude multiply disordered individuals. Finally, future studies that focus on
      isolating predictors of relapse and abstinence could make substantive
      contributions to improving treatment for individuals with co-occurring substance
      use and mental health disorders.

PMID- 16406198
TI  - How much time is needed for hand hygiene in intensive care? A prospective trained
      observer study of rates of contact between healthcare workers and intensive care
      patients.
AB  - There are few data measuring rates of contact by healthcare workers (HCWs) with
      intensive care unit (ICU) patients (direct contacts) and their immediate
      environment (indirect contacts), or estimates of the time needed for 100% hand
      hygiene compliance. We measured this using a prospective trained observer study
      in a 12-bedded UK adult general ICU admitting > 600 mixed medical/surgical
      patients annually. HCWs were observed in ICU bed spaces for 1-h periods by a
      single researcher using a pre-determined plan, such that all 12 beds were
      observed for similar times and throughout the day. Mean daily rates of direct and
      indirect contact between HCWs and ICU patients were calculated. Observed post
      contact hand hygiene compliance was also measured. Numbers of contacts/day that
      were or were not followed by hand hygiene, and estimates of the time needed daily
      for 100% compliance were calculated. On average, each patient was contacted
      directly 159 [95% confidence intervals (CI) 144-178] times and contacted
      indirectly 191 (95% CI 174-210) times/day. Observed post-contact hand hygiene
      rates were 43% for direct contacts and 12% for indirect contacts. Staff
      contacting more than one patient during routine care, who carry the highest risk
      of transmitting infection between patients, made, on average, 22 direct and 107
      indirect contacts without adequate hand hygiene/patient/day. One hundred percent
      hand hygiene compliance by all healthcare workers would require about 230
      min/patient/day (100 min for direct and 130 min for indirect contacts).

PMID- 16406199
TI  - Antimicrobial prophylaxis in clean surgery with special focus on inguinal hernia
      repair with mesh.
AB  - Until recently, antimicrobial prophylaxis was thought to be unnecessary for clean
      surgery except when a foreign body is implanted or the presence of infection
      poses a significant risk to patients. However, the results of several trials
      support extending the administration of antimicrobial prophylaxis to other types
      of clean surgery such as inguinal hernia repair or breast surgery. A recent
      Cochrane meta-analysis concluded that antimicrobial prophylaxis for inguinal
      hernia repair with or without mesh cannot be recommended or discarded. Resolution
      of this problem is important because inguinal hernia repair with mesh is one of
      the most common procedures in general surgery, and antibiotic consumption for
      preventive purposes is becoming a serious problem due to the risk of contribution
      to development of bacterial resistance and the significant increase in healthcare
      costs. This review will document clinical trials and meta-analyses on clean
      surgery, and will focus on inguinal hernia repair with mesh.

PMID- 16406200
TI  - Exposure to extrinsic risk factors in prevalence surveys of hospital-acquired
      infections: a methodological approach.
AB  - The difficulties encountered in studying the presence of extrinsic risk factors
      in the framework of prevalence surveys of hospital-acquired infections (HAI) have
      led to the use of a variety of methodological approaches. This study examined the
      effect of retrospective approaches for obtaining data regarding exposure to
      extrinsic risk factors. The EPINE database for 1990 was used and a simulation
      model was created. All the evaluated approaches differed in their impact upon the
      association between risk factors and infections. Prevalence of exposure on the
      day of the survey, prevalence of exposure at any time before the survey was
      conducted, and total prevalence were found to be significantly associated with
      the probability of exposure and duration of exposure. For exposure periods of
      less than four days, the prevalence of exposure during the week prior to the
      survey was higher than that encountered on the day of the survey. In studying
      exposure to risk factors retrospectively, no evidence-based justification could
      be found to determine how many days prior to the day of actual exposure should be
      included in the study. However, the site of infection determined the proportion
      of devices removed due to HAI, and this proportion was not very high in this
      study. Limiting data to recording the presence of the risk factor on the day of
      the survey, without investigating past exposures, can provide an adequate
      estimate of the burden of extrinsic risk factors in one-day, point-prevalence
      surveys.

PMID- 16406201
TI  - Increased use of mental health services related to isotretinoin treatment: a 5
      year analysis.
AB  - BACKGROUND: The association between exposure to Isotretinoin, the development of
      depression and suicide attempts is controversial. OBJECTIVE: To retrospectively
      assess pattern of utilization of mental health services in the Israeli Defense
      Forces (IDF) during a 5-year period for all subjects exposed to Isotretinoin in
      comparison to a control group consisting of army conscripts suffering from
      psoriasis. All subjects were young adults (18 to 21 years old) in compulsory
      military service. METHOD: Exposure to Isotretinoin mandates reporting and marking
      as a coded medical profile in the IDFs' computerized medical record of each
      conscript and soldier. Medical data, tracked by military medical profiles, were
      summarized from medical records of all subjects treated by Isotretinion during
      the years 1999-2003 and for the control group for the same period. Use of mental
      health services was the a-priori defined primary outcome measure. RESULTS: During
      the study period 1419 subjects were exposed to Isotretinoin and 1102 suffered
      from psoriasis. Utilization of mental health services was highest for the index
      group wherein 17.2% (245/1419) of subjects were evaluated or treated compared to
      12.5% in the control group (psoriasis). The inter-group differences were
      statistically significant; Chi-square=15.9 (df=2), p=0.0003. CONCLUSIONS: We
      suggest that psychiatric evaluation be regularly undertaken prior to initiation
      of Isotretinion treatment in young adults at risk, as well as providing follow-up
      visits during and at completion of treatment.

PMID- 16406202
TI  - Pituitary adenylate cyclase-activating peptide (PACAP): assessment of dipeptidyl
      peptidase IV degradation, insulin-releasing activity and antidiabetic potential.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP) is a member of the
      glucagon family of peptides. Like other members, most notably glucagon-like
      peptide-1 (GLP-1), PACAP is rapidly degraded by dipeptidylpeptidase IV (DPP IV).
      This study investigated how degradation by DPP IV affected the insulinotropic
      activity of PACAP, and whether PACAP exerted acute antihyperglycemic properties
      in normal or ob/ob mice. DPP IV degradation of PACAP(1-27) over 18 h led to the
      formation of PACAP(3-27), PACAP(5-27) and ultimately PACAP(6-27). In contrast to
      1.4-1.8-fold concentration-dependent stimulation of insulin secretion by PACAP(1
      27), these peptide fragments lacked insulinotropic activity. While PACAP(1-27)
      and PACAP(1-38) generated significant insulin responses when given alone or
      together with glucose in ob/ob and normal mice, they also elevated plasma
      glucose. These actions were eliminated following degradation of the peptide by
      incubation with DPP IV. The hyperglycemic effects may be explained at least
      partly by a potent glucagon-releasing action in ob/ob and normal mice. In
      conclusion, PACAP is inactivated by DPP IV and despite insulin-releasing effects,
      its actions on glucagon secretion and glucose homeostasis do not make it a good
      therapeutic tool for the treatment of type 2 diabetes.

PMID- 16406203
TI  - Proenkephalin peptide F immunoreactivity in different circulatory biocompartments
      after exercise.
AB  - This study was the first study to examine the three circulatory biocompartments
      (plasma, white blood cell layer (WBC) and red blood cell layer (RBC)) and
      determine PF concentrations before and after exercise. Proenkephalin peptide F
      (PF) is an enkephalin-containing peptide found predominantly within the adrenal
      medulla. PF is co-packaged with epinephrine, and both can be co-secreted in
      response to similar stimuli. PF and epinephrine have shown immunomodulating
      properties. Ten healthy resistance trained men performed six sets of 10 RM squats
      with 2 min rest periods between sets and 10 healthy active men were matched and
      served as resting controls. Blood samples were obtained pre-exercise, immediately
      post-exercise and 15 min post-exercise and were analyzed for lactate, cortisol,
      epinephrine and biocompartmentalized PF. There was no change in resting control
      values measured across time within respective PF biocompartments and endocrine
      profile, indicating stability and technique validity of peptide F across the time
      period measured. As expected, the acute resistance exercise protocol caused an
      increase in lactate at 15 min post-exercise. Circulating epinephrine increased
      immediately post-exercise and returned to baseline during 15 min into recovery.
      Plasma PF increased immediate post-exercise and 15 min post-exercise, while WBC
      PF and RBC-PF only increased at 15 min into recovery. For all time points tested,
      resting and exercise WBC-PF and RBC-PF concentrations were lower than plasma PF
      thus indicating a concentration difference across the three different
      biocompartments within the same blood sample. The presence of PF within all three
      biocompartments of whole blood may indicate the potential for biological
      transport and interactions with other cells in other biocompartments of the
      blood.

PMID- 16406204
TI  - Catabolism of the octadecaneuropeptide ODN by prolyl endopeptidase:
      identification of an unusual cleavage site.
AB  - The octadecaneuropeptide ODN (QATVGDVNTDRPGLLDLK), a biologically active fragment
      of diazepam-binding inhibitor, exerts a number of behavioral and
      neurophysiological activities. The presence of a proline residue in the sequence
      of ODN led us to investigate the role of proline endopeptidase (PEP) in the
      catabolism of this neuropeptide. The effect of PEP on the breakdown of ODN and
      related analogs was studied by combining RP-HPLC analysis and MALDI-TOF MS
      characterization. Incubation of ODN with PEP generated two products, i.e. ODN3-18
      and ODN5-18 which resulted from cleavage of the Ala-Thr and Val-Gly peptide
      bonds. S 17092, a specific PEP inhibitor, significantly reduced the PEP-induced
      cleavages of ODN. Similarly, [Ala2]OP showed S 17092-sensitive post-alanine
      cleavage, while [pGlu1]ODN and OP (ODN11-18) were not catabolized by the enzyme.
      For all these peptides, cleavage of the Pro-Gly peptide bond by PEP was never
      observed, even after prolonged incubation times. In contrast, PEP hydrolyzed
      human urotensin II at the canonical post-proline site. Collectively, these data
      suggest that the Ala2 residue is the preferential cleavage site of ODN and that
      the Pro-Gly bond of ODN is not hydrolyzed by PEP. In addition, this study reveals
      for the first time that the endoproteolytic activity of PEP can specifically take
      place after a valine moiety.

PMID- 16406205
TI  - Conceptual and perceptual memory: retrieval orientations reflected in event
      related potentials.
AB  - In memory retrieval, search can be guided by mental sets towards different
      subsets of the available evidence. Such retrieval orientations have been
      suggested to leave an imprint on event-related potentials (ERPs). The present
      study aimed at characterizing orientations towards perceptual and conceptual
      evidence in a recognition task, where pictures and words were studied. In the
      recognition test, items were presented in either the same format as at study or
      in the opposite format. A between-subjects manipulation modified the task,
      instructing an Exclusion group to endorse only items that preserved their format
      from study, and an Inclusion group to endorse both formats of a studied item. It
      was hypothesized that exclusion instructions would instill a perceptual and
      inclusion instructions a conceptual orientation. As a corollary, instructions
      were expected to dissociate the high end from the low end of the picture-word
      mirror effect. This expectation was confirmed in a behavioural experiment. In an
      ERP experiment, retrieval orientations were examined in their effects on correct
      rejections of new pictures and words. Confirming earlier findings [Hornberger,
      M., Morcom, A. M., & Rugg, M. D. (2004). Neural correlates of retrieval
      orientation: effects of study-test similarity. Journal of Cognitive Neuroscience,
      16(7), 1196-1210], a perceptual orientation was accompanied by more positive
      going amplitudes over widespread areas. The difference was larger for pictures
      than for words, supporting behavioural evidence that new pictures are more easily
      rejected on perceptual grounds than are new words. The Exclusion group showed no
      ERP evidence of cross-format old-new effects, despite reaction times indicative
      of involuntary conceptual recognition. The results indicate that perceptual and
      conceptual retrieval orientations imprint distinct signatures on ERPs. They
      further suggest that the examined old-new effects in ERPs are mainly linked to
      voluntary aspects of memory, even in a task where involuntary memory exerts
      effects on reaction times.

PMID- 16406206
TI  - Challenges to the reproductive-health needs of African women: on religion and
      maternal health utilization in Ghana.
AB  - How relevant is religion to our understanding of maternal health (MH) service
      utilization in sub-Saharan Africa? We ask this question mainly because while the
      effect of religion on some aspects of reproductive behavior (e.g., fertility,
      contraception) has not gone unnoticed in the region, very few studies have
      examined the possible link with MH service utilization. Understanding this link
      in the context of sub-Saharan Africa is particularly relevant given the
      overriding influence of religion on the social fabric of Africans and the
      unacceptably high levels of maternal mortality in the region. As African
      countries struggle to achieve their stipulated reductions in maternal and child
      mortality levels by two-thirds by 2015 as part of the Millennium Development
      Goals, the need to examine the complex set of macro- and micro-factors that
      affect maternal and child health in the region cannot be underestimated. Using
      data from the 2003 Ghana Demographic Survey, we found religion (measured by
      denominational affiliation) to be a significant factor in MH use. This is true
      even after we had controlled for socio-economic variables. In general, Moslem and
      traditional women were less likely to use such services compared with Christians.
      The findings are discussed with reference to our theoretical framework and some
      policy issues are highlighted.

PMID- 16406207
TI  - Development, validation and utility of an in vitro technique for assessment of
      potential clinical drug-drug interactions involving P-glycoprotein.
AB  - Regulatory interest is increasing for drug transporters generally and P
      glycoprotein (Pgp) in particular, primarily in the area of drug-drug
      interactions. To aid in both identifying and discharging the potential
      liabilities associated with drug-transporter interactions, the pharmaceutical
      industry has a growing requirement for routine and robust non-clinical assays. An
      assay was designed, optimised and validated to determine the in vitro inhibitory
      potency of new chemical entities (NCEs) towards human Pgp-mediated transport.
      [3H]-Digoxin was established as a suitable probe substrate by investigating its
      characteristics in the in vitro system (MDCKII-MDR1 cells grown in 24-multiwell
      inserts). The inhibitory potencies (apparent IC50) of known Pgp inhibitors
      astemizole, GF120918, ketoconazole, itraconazole, quinidine, verapamil and
      quinine were determined over at least a 1000-fold concentration range. Validation
      was carried out using manual and automatic techniques. [3H]-Digoxin was found to
      be stable and have good mass balance in the system. In contrast to [A-->B]
      transport, [3H]-digoxin [B-->A] transport rates were readily measured with good
      reproducibility. There was no evidence of saturation of transport up to 10 microM
      digoxin and 30 nM digoxin was selected for routine assay use, reflecting clinical
      therapeutic concentrations. IC50 values ranged over approximately 100-fold with
      excellent reproducibility. Results from manual and automated versions were in
      close agreement. This method is suitable for routine use to assess the in vitro
      inhibitory potency of NCEs on Pgp-mediated digoxin transport. Comparison of IC50
      values against clinical interaction profiles for the probe inhibitors indicated
      the in vitro assay is predictive of clinical digoxin-drug interactions mediated
      via Pgp.

PMID- 16406208
TI  - [Molecular genetics of cardiac arrhythmias].
AB  - INTRODUCTION: Recent progress in molecular biology led to the identification of
      the genes involved in various cardiac arrhythmias causing syncope and sudden
      death in young people. EXEGESIS: This article briefly describes the clinical
      features and the genes associated with the congenital long QT syndrome, the short
      QT syndrome, Brugada's syndrome, catecholaminergic polymorphic ventricular
      tachycardias and arrhythmogenic right ventricular dysplasia. CONCLUSION:
      Identification of genetic variations that cause cardiac tachyarrhythmias can help
      to identify at risk-patients and to propose clinical follow-up and preventive
      therapy. Further studies are needed to discover other cardiac genetic disorders
      and to understand cellular mechanisms involved in these diseases.

PMID- 16406209
TI  - Recovery and purification of highly aggregation-prone disulfide-containing
      peptides: application to islet amyloid polypeptide.
AB  - Islet amyloid polypeptide (IAPP) is a 37-residue pancreatic hormone. It is
      responsible for the formation of islet amyloid in vivo and is very insoluble and
      aggregation-prone in vitro, particularly at basic pH. The peptide contains a
      disulfide bridge between residues two and seven and an amidated C terminus. There
      is no reported expression system for the production of amidated IAPP. The peptide
      is difficult to synthesize and formation of the disulfide by traditional methods
      is problematic. We have found that the use of 1,1,1,3,3,3-hexafluoro-2-propanol
      (HFIP) or dimethyl sulfoxide (DMSO) significantly improves disulfide formation
      and purification of highly aggregation-prone IAPP sequences. The use of these
      organic solvents increases the solubility of the hydrophobic peptides, avoids the
      use of aqueous basic solutions, and eliminates the need for continuous stirring
      during oxidation to form the Cys-2 to Cys-7 disulfide bridge. Elimination of the
      stirring step and basic solution helps to reduce aggregation and allows for more
      consistent high-performance liquid chromatography (HPLC) retention times.
      Formation of the intramolecular disulfide using DMSO was found to be the most
      effective method for IAPP oxidation, reducing the reaction time from 24 to 5 h.
      Aggregated IAPP can be resolubilized by HFIP or DMSO and recovered by HPLC with
      very good yield.

PMID- 16406210
TI  - Selective endothelin a (ETA) receptor antagonist (BQ-123) reduces both myocardial
      infarct size and oxidant injury.
AB  - OBJECTIVE: Endothelins (ET) can be considered stress-responsive regulators
      working in paracrine and autocrine fashion. It has been suggested that elevated
      levels of ET may be responsible for the low coronary re-flow phenomena. Ischemia
      reperfusion (I/R) was shown to stimulate ET release in rat heart; however, the
      mechanism(s) of this effect has not been clarified. Therefore, this study was
      focused to investigate the effect of BQ-123, selective ETA receptor antagonist,
      on three aspects of myocardial ischemia-reperfusion (MI/R) injury: hemodynamic
      parameters, infarct size and oxidant-antioxidant status in the absence and
      presence of ET-1 in an vivo rat model. METHODS AND RESULTS: To produce MI/R, a
      branch of the descending left coronary artery was occluded for 30 min followed by
      2h reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were
      measured before occlusion and continued both occlusion and reperfusion. Forty
      rats were randomly assigned to five groups equally: (1) sham-operated rats
      without coronary ligation, (2) I/R group, (3) I/R+BQ-123-treated group (10
      microg/kg/min i.v.), (4) I/R+ET-treated group (25 ng/kg/min i.v.), (5) I/R+ET+BQ
      123-treated group. The results are expressed as mean+/-S.E.M. In the ET-1 plus
      I/R group, the ratio between the infarcted area and area at risk 56+/-1% was
      significantly higher than I/R group (49+/-1%). In the BQ-123 group with or
      without exogenous ET-1 treatment in I/R group, this ratio was significantly lower
      at 40+/-2 and 37+/-1%, respectively. As compared to sham group, I/R increased
      lipid peroxidation whereas decreased nitric oxide (NO), glutathione (GSH),
      catalase (CAT) and superoxide dismutase (SOD) contents. This decreased
      antioxidant enzymatic defense could result in aggravated oxidative damage in I/R
      group rat hearts. ET-1 administration group showed severe oxidative damage. BQ
      123 administrations to I/R group with or without ET-1 caused significantly
      decrease in lipid peroxidation and increased in SOD, CAT activities and NO
      generation and GSH content when compared with I/R group alone. CONCLUSIONS: The
      most important finding of the present study is that the ET blockade reduced I/R
      induced myocardial injury. The mechanism of this reduction was speculated to be a
      resistance to ischemic injury in the subcellular levels of the myocardium
      conferred by a reduction of vascular constriction and improvement of imbalance in
      the antioxidant status.

PMID- 16406211
TI  - On tracks and locomotives: the long route of DNA to the nucleus.
AB  - Molecular motors have prominent functions in organelle transport, cytoskeletal
      organization, division and motility. The dyneins are one of the three families of
      cytoskeleton-based molecular motors and they travel along the cytoplasmic
      microtubule network towards the minus end of the microtubule. This directed
      movement is used by DNA viruses to deliver their infectious genome and proteins
      to the host cell nucleus. In recent studies, it has been hypothesized that
      Agrobacterium species use a similar pathway to deliver their infectious unit--a
      large complex between single-stranded DNA and proteins--to the host cell nucleus
      and that a karyophilic protein carrier that can deliver synthetic DNA to the
      nucleus is also driven by a dynein motor. These studies shed light on the
      mechanism of Agrobacterium-mediated genetic transformation and could lead to new
      methods for the efficient transfection of synthetic DNA.

PMID- 16406212
TI  - Clinical education facilitators' and post-registration paediatric student nurses'
      perceptions of the role of the clinical education facilitator.
AB  - In Ireland the past two decades have witnessed the introduction of various
      clinical 'support' personnel under various titles into clinical areas. However,
      an identifiable gap remains with a degree of ambiguity over who has prime
      responsibility for clinical teaching. Now, a new post has emerged, that of
      clinical education facilitators (CEFs). To date this role has not been
      empirically explored. The purpose of this study was to explore the CEF role from
      the perspective of facilitators themselves and post-registration paediatric
      nursing students, one cohort the CEFs have responsibility for. Using an
      exploratory descriptive design focus group interviews were employed to collect
      data from a volunteer sample. The CEF role emerged as diverse, complex and
      multifaceted with the CEF coordinating factors in the clinical environment to
      make it function as an effective learning environment for students. Four main
      strategies were employed: facilitating transition, maximising learning
      opportunities, preparing the clinical environment and providing support. This
      study offers preliminary evidence towards clarification of the nature and purpose
      of the CEF role. The central recommendation is the urgent need to define the role
      so all stakeholders share a common understanding of the activities of the role
      holder.

PMID- 16406214
TI  - Isolation of a latent polyphenol oxidase from loquat fruit (Eriobotrya japonica
      Lindl.): kinetic characterization and comparison with the active form.
AB  - Polyphenol oxidase (PPO) has been extracted from both soluble and particulate
      fractions of loquat fruit (Eriobotrya japonica Lindl. cv. Algerie). The soluble
      PPO (20% of total activity) was partially purified 3.3-fold after ammonium
      sulfate fractionation being in its active state. The particulate PPO fraction
      (80% of total activity) was purified to homogeneity in a latent form being
      activable by sodium dodecyl sulfate (SDS). The enzyme was purified 40.0-fold with
      a total yield of 15.3% after extraction by phase partitioning in Triton X-114
      followed by three chromatographic steps. The molecular weight was estimated to be
      about 59.2 and 61.2 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and gel filtration chromatography, respectively,
      indicating that latent PPO is a monomer. Latent PPO catalyzed the oxidation of
      chlorogenic acid (CA) at a rate 50-fold faster than that of 4-tert-butylcatechol
      (TBC) but the soluble active counterpart only twice. Both PPOs exhibited similar
      Km values for TBC but Km for CA was 5-fold higher for the latent than for the
      active soluble PPO. Other kinetic characteristics, including sensitivity to
      inhibitors, substrate specificity, thermal stability, temperature, and pH
      profiles, were quite different between both PPOs. These results provide strong
      evidences that the soluble active and the particulate latent are different forms
      of PPO in loquat fruit flesh. The results suggest that the major PPO form for the
      oxidation of CA, leading to enzymatic browning under physiological conditions, is
      the latent one.

PMID- 16406215
TI  - Personality correlates of startle habituation.
AB  - This study investigated the relationship between extraversion and rates of
      acoustic startle habituation, a potential biological marker for individual
      differences. Personality was measured using the Eysenck Personality Questionnaire
      (EPQ), the Sensation Seeking Scale (SSS), and Tellegen's Multidimensional
      Personality Questionnaire (MPQ). Higher EPQ Extraversion and higher SSS scores
      were associated with faster, more rapid startle habituation. Moreover, the
      relationship between extraversion and faster startle habituation was replicated
      in a second, follow-up sample. Within the initial study sample, lower scores on
      the Constraint (CON) factor of the MPQ (reflecting greater impulsiveness, risk
      taking, and nonconformity) were also associated with faster startle habituation.
      Follow-up analyses revealed relationships between EPQ Extraversion, SSS, and low
      MPQ CON. These results suggest that faster habituation within the CNS may be
      associated tendencies toward impulsivity and behavioral disinhibition.

PMID- 16406213
TI  - Detection of dideoxyosone intermediates of glycation using a monoclonal antibody:
      characterization of major epitope structures.
AB  - Glycation or the Maillard reaction in proteins forms advanced glycation end
      products (AGEs) that contribute to age- and diabetes-associated changes in
      tissues. Dideoxyosones, which are formed by the long-range carbonyl shift of the
      Amadori product, are newly discovered intermediates in the process of AGE
      formation in proteins. They react with o-phenylenediamine (OPD) to produce
      quinoxalines. We developed a monoclonal antibody against 2-methylquinoxaline-6
      carboxylate coupled to keyhole limpet hemocyanin. The antibody reacted strongly
      with ribose and fructose (+OPD)-modified RNase A and weakly with glucose and
      ascorbate (+OPD)-modified RNase A. Reaction with substituted quinoxalines
      indicated that this antibody favored the 2-methyl group on the quinoxaline ring.
      We used high performance liquid chromatography to isolate and purify three
      antibody-reactive products from a reaction mixture of N alpha-hippuryl-L
      lysine+ribose+OPD. The two most reactive products were identified as
      diastereoisomers of N1-benzoylglycyl-N6-(2-hydroxy-3-quinoxalin-2-ylpropyl)lysine
      and the other less reactive product as N1-benzoylglycyl-N6-[2-hydroxy-2-(3
      methylquinoxalin-2-yl)ethyl]lysine. Our study confirms that dideoxyosone
      intermediates form during glycation and offers a new tool for the study of this
      important pathway in diabetes and aging.

PMID- 16406216
TI  - Influence of individual differences in the Behavioral Inhibition System and
      stimulus content (fear versus blood-disgust) on affective startle reflex
      modulation.
AB  - Inconsistencies among affective startle reflex modulation studies may be due to
      differences in the startle potentiation produced by the specific content of the
      images used, to individual differences in sensitivity to negative stimuli, or to
      the interaction of both factors. To explore this interaction, 52 undergraduates
      obtaining extreme scores on a self-report measure of the Behavioral Inhibition
      System (BIS) participated in an affective startle reflex modulation paradigm. A
      significant interaction between BIS group (high versus low) and image content
      emerged from the MANOVA. Comparing startle magnitude between fear and pleasant
      images, low BIS participants did not seem to show startle potentiation, whereas
      high BIS participants did. Both groups displayed potentiated startle during blood
      disgust images. The present results suggest the importance of considering
      personality variables and their interaction with image content in the affective
      startle modulation paradigm.

PMID- 16406217
TI  - Polarimetric imaging of amyloid.
AB  - New developments in optical microscopy are discussed with relevance to the
      imaging of amyloid plaques that are pathognomonic of a variety of degenerative
      disorders. We present the results of linear birefringence, linear dichroism, and
      circular dichroism imaging of Congo red stained plaques ex vivo and in vitro. A
      new technique for measuring rapid changes in linear anisotropies is introduced.
      The application of polarimetric imaging as demonstrated here can be extended to
      broader pathological practice since polarimetric measurements are sensitive to
      transformations in tissues that are specific disease signatures.

PMID- 16406218
TI  - Home enteral nutrition in children: a 17-year period experience.

PMID- 16406219
TI  - The effects of angry and happy expressions on recognition memory for unfamiliar
      faces in delusion-prone individuals.
AB  - Numerous studies suggest a cognitive bias for threat-related material in
      delusional ideation. However, few studies have examined this bias using a memory
      task. We investigated the influence of delusion-proneness on identity and
      expression memory for angry and happy faces. Participants high and low in
      delusion-proneness were presented with happy and angry faces and were later asked
      to recognise the same faces displaying a neutral expression. They also had to
      remember what the initial expressions of the faces had been. Remember/know/guess
      judgments were asked for both identity and expression memory. Results showed that
      delusion-prone participants better recognised the identity of angry faces
      compared to non-delusional participants. Also, this difference between the two
      groups was mainly due to a greater number of remember responses in delusion-prone
      participants. These findings extend previous studies by showing that delusions
      are associated with a memory bias for threat-related stimuli.

PMID- 16406220
TI  - Incidence of parvovirus B19 infection among an unselected population of pregnant
      women in the Netherlands: A prospective study.
AB  - OBJECTIVE: To evaluate seroprevalence of anti-parvovirus B19 IgG immunoglobulins
      and the rate of seroconversion in seronegative pregnant women. DESIGN:
      Prospective assessment of anti-parvovirus B19 IgG immunoglobulins in an
      unselected population of pregnant women booked for antenatal care from 1998 to
      2000. SETTING: Maternity departments of an academic hospital and four affiliated
      teaching hospitals in the Netherlands. SUBJECTS: Two thousand five hundred and
      sixty seven pregnant women. MAIN OUTCOME MEASURES: Seroprevalence of anti
      parvovirus B19 IgG immunoglobulin in the first trimester of pregnancy and
      subsequent seroconversion in those women who were tested negative for parvovirus
      B19 antibodies in the first trimester of pregnancy. RESULTS: The estimated
      seroprevalence of anti-parvovirus B19 IgG immunoglobulins among the study
      population is 70% (95% CI: 68-71) in the first trimester of pregnancy. Seven
      hundred and seventy nine women tested negative for parvovirus B19 antibodies in
      the first trimester of pregnancy. Paired testing in these women confirmed 18
      seroconversions. Based on these findings the estimated incidence of maternal
      parvovirus B19 infection in this population among seronegative Dutch women is
      2.4% (95% CI: 1.4-3.7). CONCLUSION: Maternal infection with parvovirus B19 is
      relatively common. However, it is argued that in the Netherlands routine
      assessment of parvovirus antibodies in pregnant women is not warranted as there
      is a low risk of adverse fetal outcome and measures to prevent the parvovirus B19
      infection and its consequences are very limited.

PMID- 16406221
TI  - Induction of labor with misoprostol in pregnancies with advanced maternal age.
AB  - OBJECTIVE: The objective was to compare the efficacy and complications of
      intravaginal misoprostol application with oxytocin infusion for induction of
      labor in advanced aged pregnancies with a Bishop score of < 6. STUDY DESIGN: A
      hundred advanced aged (> or = 35 years) pregnant patients with a Bishop score of
      < 6 were randomized into two groups. The first group (50 patients) received 50
      microg intravaginal misoprostol four times with 4 h intervals and the second
      group received oxytocin infusion for induction of labor starting from 2 mIU/min
      and was increased every 30 min with 2 mIU/min increments up to a maximum of 40
      mIU/min. The time from induction to delivery, the route of delivery, fetal
      outcome, and maternal complications were recorded. Statistical analyses were
      performed using the Mann-Whitney U, Chi-squared and t tests to determine
      differences between the two groups. A p value < or = 0.05 was considered
      significant. RESULTS: Misoprostol was superior for induction of labor in advanced
      aged pregnancies with Bishop score of < 6, as the mean time from induction to
      delivery was 9.61 +/- 4.12 h and 11.46 +/- 4.86 h in the misoprostol and oxytocin
      groups respectively, with a significant difference between the groups (p = 0.04).
      The rate of vaginal delivery was higher in the misoprostol group (84.0%) than in
      the oxytocin group (80.0%), but the difference did not reach significance (p =
      0.60). The rates of placental abruption and postpartum hemorrhage were similar in
      both groups and no cases of uterine rupture occurred. The 1- and 5-min mean Apgar
      scores were 6.98 +/- 1.17 to 9.08 +/- 0.99 and 6.88 +/- 1.81 to 9.00 +/- 1.35 in
      the misoprostol and oxytocin groups respectively, with no significant differences
      between the groups (p = 0.74, p = 0.83). No cases of asphyxia were present. The
      rate of admission to the neonatal intensive care unit was similar in both groups.
      CONCLUSION: Intravaginal misoprostol seems to be an alternative method to
      oxytocin in the induction of labor in advanced aged pregnant women with low
      Bishop scores, as it is efficacious, cheap, and easy to use. But large studies
      are necessary to clarify safety with regard to the rare complications such as
      uterine rupture.

PMID- 16406222
TI  - The impact of graft size on the development of dyskinesia following intrastriatal
      grafting of embryonic dopamine neurons in the rat.
AB  - Intrastriatal transplants of embryonic ventral mesencephalon can cause dyskinesia
      in patients with Parkinson's disease (PD). We assessed the impact of transplant
      size on the development of graft-induced dyskinesia. Rats with unilateral 6
      hydroxydopamine lesions were primed to exhibit L-DOPA-induced dyskinesia. They
      were then intrastriatally grafted with different quantities of embryonic ventral
      mesencephalic tissue to give small and large grafts. Without drug treatment,
      discrete dyskinetic-like movements were observed in most rats with large grafts 2
      6 weeks after transplantation, but disappeared later. Amphetamine evoked severe
      abnormal involuntary movements (AIMs) in grafted animals, which were more
      striking with large grafts. The AIMs coincided with contralateral rotation, but
      displayed a different temporal profile and pharmacological properties. Thus,
      selective dopamine uptake blockade elicited rotational behavior, whereas
      coadministration of both dopamine and serotonin uptake blockers was required to
      evoke significant orolingual and limb AIMs. In conclusion, robust and
      reproducible AIMs were evoked in rats with large grafts by blockade of monoamine
      reuptake. These AIMs may provide a new tool for assessing dyskinetic effects of
      neural grafting.

PMID- 16406223
TI  - Isoprenoids and Alzheimer's disease: a complex relationship.
AB  - Cholesterol metabolism has been linked to Alzheimer's disease (AD)
      neuropathology, which is characterized by amyloid plaques, neurofibrillary
      tangles and neuroinflammation. Indeed, the use of statins, which inhibit
      cholesterol and isoprenoid biosynthesis, as potential AD therapeutics is under
      investigation. Whether statins offer benefit for AD will be determined by the
      outcome of large, placebo-controlled, randomized clinical trials. However, their
      use as pharmacological tools has delineated novel roles for isoprenoids in AD.
      Protein isoprenylation regulates multiple cellular and molecular events and here
      we review the complex roles of isoprenoids in AD-relevant processes and carefully
      evaluate isoprenoid pathways as potential AD therapeutic targets.

PMID- 16406224
TI  - Safety and immunogenicity of a combined DTPa-IPV vaccine administered as a
      booster from 4 years of age: a review.
AB  - A combined DTPa-IPV booster vaccine was administered as a 4th or 5th dose after
      DTPa or DTPw priming. Over 99% vaccines developed antibody levels considered to
      be protective to diphtheria, tetanus and poliovirus, and >95% mounted a response
      to acellular pertussis antigens. Rectal temperature >39.5 degrees C was observed
      in at most 3.2% of vaccinees. Swelling >50 mm occurred in 24% of DTPa-primed
      compared to 5.5% of DTPw-primed children. Large swelling involving the entire
      upper arm (extending to involve the elbow joint) was reported for up to 1.2% of
      DTPa-primed subjects, which is consistent with literature reports for other DTPa
      vaccines.

PMID- 16406225
TI  - Efficient systemic and mucosal responses against the HIV-1 Tat protein by
      prime/boost vaccination using the lipopeptide MALP-2 as adjuvant.
AB  - A major goal of HIV-1 vaccine development is the induction of mucosal immune
      responses able to stop or reduce viral infection directly at the portal of entry.
      We established a heterologous prime/boost vaccination protocol based on
      intradermal priming with the HIV-1 Tat protein and intranasal boosting with the
      Tat protein co-administered with the mucosal adjuvant MALP-2. Strong Tat-specific
      humoral responses were elicited in vaccinated mice at both systemic and mucosal
      levels. The cellular responses were characterized by a Th1 dominant helper
      pattern. The heterologous prime/boost regimen was also able to induce Tat
      specific CTL, which were absent in animals receiving the homologous prime boost
      scheme. Thus, the heterologous prime/boost protocol was the only regimen able to
      evoke both CTL and sIgA responses. This suggests that a similar approach can be
      exploited to develop multi-component vaccines against HIV-1 infections able to
      induce both systemic and mucosal immune responses.

PMID- 16406226
TI  - The epidemiology of genital human papillomavirus infection.
AB  - Clinical and subclinical human papillomavirus (HPV) infections are the most
      common sexually transmitted infections in the world, and most sexually-active
      individuals are likely to be exposed to HPV infection during their lifetimes.
      More than 40 genotypes of HPV infect the epithelial lining of the anogenital
      tract and other mucosal areas of the body; of these, 13-18 types are considered
      to be high-oncogenic risk HPV types (HR-HPV). Persistent infection with HR-HPVs
      is now unequivocally established as a necessary cause of cervical cancer and is
      likely to be responsible for a substantial proportion of other anogenital
      neoplasms and upper aero-digestive tract cancers. Low oncogenic risk HPV types
      (LR-HPV) are also responsible for considerable morbidity as the cause of genital
      warts. Youth and certain sexual characteristics are key risk factors for HPV
      acquisition and persistence of HPV infection, but other mediating factors include
      smoking, oral contraceptive (OC) use, other STIs (e.g. chlamydia, herpes simplex
      virus), chronic inflammation, immunosuppressive conditions including HIV
      infection, parity, dietary factors, and polymorphisms in the human leukocyte
      antigen system. Not surprisingly, these factors are also established or candidate
      cofactors identified in epidemiologic studies of cervical cancer. HPV
      transmissibility and molecular events in HPV-induced carcinogenesis have been the
      focus of recent multidisciplinary epidemiologic studies. This shift in research
      focus coincides with a shift in cancer prevention techniques towards immunization
      with HPV vaccines and HPV testing of precancerous lesions.

PMID- 16406227
TI  - From genome to vaccines for leishmaniasis: screening 100 novel vaccine candidates
      against murine Leishmania major infection.
AB  - The genomic sequence of Leishmania major provides a rich source of vaccine
      candidates. One hundred randomly selected amastigote-expressed genes were
      screened as DNA vaccines, and efficacy determined following high-dose L. major
      footpad challenge in BALB/c mice. Fourteen protective novel vaccine candidates
      were identified; seven vaccines exacerbated disease. There were no differences in
      the number of predicted MHC H-2d class I or II epitopes mapping to protective
      versus exacerbatory antigens. A proportion of both protective (7/14; 50%) and
      exacerbatory (4/7; 57%) proteins showed short (8- to 18-mer) 100% amino acid
      sequence identities to human, mouse or gut flora proteins. A high proportion of
      these (4/7 protective; 3/4 exacerbatory) showed full or partial overlap with
      RANKPEP-predicted H-2d classes I and II epitopes. Our data suggest, therefore,
      that there may be little difference between antigens/epitopes that drive
      regulatory versus effector CD4 T cell populations. The best novel protective
      antigen was an amastin-like gene that maps to a 17-gene tandem array on
      Leishmania chromosome 8 and is closely related to 37 other amastin-like genes.
      Two ribosomal proteins, a V-ATPase subunit, and a dynein light chain orthologue
      were the only other protective genes with putative functions.

PMID- 16406229
TI  - Transport and fate of radionuclides in aquatic environments--the use of ecosystem
      modelling for exposure assessments of nuclear facilities.
AB  - In safety assessments of nuclear facilities, a wide range of radioactive isotopes
      and their potential hazard to a large assortment of organisms and ecosystem types
      over long time scales need to be considered. Models used for these purposes have
      typically employed approaches based on generic reference organisms, stylised
      environments and transfer functions for biological uptake exclusively based on
      bioconcentration factors (BCFs). These models are of non-mechanistic nature and
      involve no understanding of uptake and transport processes in the environment,
      which is a severe limitation when assessing real ecosystems. In this paper,
      ecosystem models are suggested as a method to include site-specific data and to
      facilitate the modelling of dynamic systems. An aquatic ecosystem model for the
      environmental transport of radionuclides is presented and discussed. With this
      model, driven and constrained by site-specific carbon dynamics and three
      radionuclide specific mechanisms: (i) radionuclide uptake by plants, (ii)
      excretion by animals, and (iii) adsorption to organic surfaces, it was possible
      to estimate the radionuclide concentrations in all components of the modelled
      ecosystem with only two radionuclide specific input parameters (BCF for plants
      and Kd). The importance of radionuclide specific mechanisms for the exposure to
      organisms was examined, and probabilistic and sensitivity analyses to assess the
      uncertainties related to ecosystem input parameters were performed. Verification
      of the model suggests that this model produces analogous results to empirically
      derived data for more than 20 different radionuclides.

PMID- 16406230
TI  - "Transuranium radionuclide pollution in the waters of the la Maddalena National
      Marine Park": burden of proof inadequate for the conclusions.

PMID- 16406228
TI  - MALDI-TOF and ESI-MS analysis of oligosaccharides labeled with a new
      multifunctional oligosaccharide tag.
AB  - A new multifunctional oligosaccharide label with a 1 degree amino-group was
      synthesized and characterized. The oligosaccharide label was introduced into
      several neutral oligosaccharides by reductive amination, and the derivatives were
      analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight
      (TOF) and by electrospray ionization (ESI) mass spectrometry. It was demonstrated
      that the labeling reaction was satisfactory, and that as little as 50 pmol of
      starting material could be efficiently labeled with minimal loss to side
      reactions. A mixture of high-mannose N-glycans released from ribonuclease B was
      labeled. The label did not appear to interfere with structural characterization
      of the oligosaccharides by mass spectrometry. N-quaternization of the labeled
      oligosaccharides resulted in significantly increased sensitivity of detection
      with as little as 100 fmol on the probe detected. Deuterium coding of labeled
      oligosaccharide mixtures and relative abundance of mixture components was
      investigated. A protocol for the chromatographic separation of mixtures of
      labeled oligosaccharides by HPLC was developed and is reported here.

PMID- 16406231
TI  - An RNA foldability metric; implications for the design of rapidly foldable RNA
      sequences.
AB  - Evidence is presented suggesting, for the first time, that the protein
      foldability metric sigma = (T(theta)-T(f))/T(theta), where T(theta) and T(f) are,
      respectively, the collapse and folding transition temperatures, could be used
      also to measure the foldability of RNA sequences. These results provide further
      evidence of similarities between the folding energy landscapes of proteins and
      RNA. The importance of sigma is discussed in the context of the in silico design
      of rapidly foldable RNA sequences.

PMID- 16406232
TI  - NMDA receptors mediate calcium-dependent, bidirectional changes in dendritic
      PICK1 clustering.
AB  - AMPA receptor (AMPAR) trafficking at CNS synapses is regulated by several
      receptor-binding proteins. One model of AMPAR endocytosis entails the cotargeting
      of the GluR2-interacting protein PICK1 and activated PKC to synapses. We
      demonstrate that NMDA receptor (NMDAR) activation mediates bidirectional changes
      in surface AMPARs through two additional forms of PICK1 redistribution. In
      neurons, NMDAR activation, which induces AMPAR endocytosis, increases endosomal
      PICK1 clustering. In contrast, stronger NMDAR activation rapidly reduces PICK1
      clustering accompanied by decreases in PICK1/GluR2 association and increases in
      surface AMPAR levels. PICK1-siRNA similarly increases surface AMPARs and occludes
      the NMDAR-mediated effect, demonstrating the role of PICK1 in this process.
      Bidirectional NMDAR-mediated changes in PICK1 localization are determined by the
      magnitude of receptor-activated dendritic calcium signals. Our results show that
      PICK1 localization in dendrites is subject to multiple forms of regulation that
      contribute to surface AMPAR expression, likely by modulating the numbers of
      AMPARs maintained in intracellular compartments.

PMID- 16406233
TI  - Using multivariate analyses and GIS to identify pollutants and their spatial
      patterns in urban soils in Galway, Ireland.
AB  - Galway is a small but rapidly growing tourism city in western Ireland. To
      evaluate its environmental quality, a total of 166 surface soil samples (0-10 cm
      depth) were collected from parks and grasslands at the density of 1 sample per
      0.25 km2 at the end of 2004. All samples were analysed using ICP-AES for the near
      total concentrations of 26 chemical elements. Multivariate statistics and GIS
      techniques were applied to classify the elements and to identify elements
      influenced by human activities. Cluster analysis (CA) and principal component
      analysis (PCA) classified the elements into two groups: the first group
      predominantly derived from natural sources, the second being influenced by human
      activities. GIS mapping is a powerful tool in identifying the possible sources of
      pollutants. Relatively high concentrations of Cu, Pb and Zn were found in the
      city centre, old residential areas, and along major traffic routes, showing
      significant effects of traffic pollution. The element As is enriched in soils of
      the old built-up areas, which can be attributed to coal and peat combustion for
      home heating. Such significant spatial patterns of pollutants displayed by urban
      soils may imply potential health threat to residents of the contaminated areas of
      the city.

PMID- 16406234
TI  - In defence of plants as biomonitors of soil quality.
AB  - Biomonitors are organisms that provide quantitative information on environmental
      quality. There are some constraints and limitations for the use of plants as
      biomonitors of soil pollution, as pointed out recently by some authors in this
      journal. However, we defend the use of plants as biomonitors, and argue that they
      have important advantages over soil analyses as indicators of soil quality,
      particularly when investigations are made on a large scale.

PMID- 16406235
TI  - The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.
AB  - The amyloid precursor protein (APP) is the source of amyloid-beta (Abeta)
      peptide, produced via its sequential cleavage beta- and gamma-secretases. Various
      biophysical forms of Abeta (and the mutations of APP which results in their
      elevated levels) have been implicated in the etiology and early onset of
      Alzheimer's disease. APP's evolutionary conservation and the existence of APP
      like isoforms (APLP1 and APLP2) which lack the Abeta sequence, however, suggest
      that these might have important physiological functions that are unrelated to
      Abeta production. Soluble N-terminal fragments of APP have been known to be
      neuroprotective, and the interaction of its cytoplasmic C-terminus with a myriad
      of proteins associates it with diverse processes such as axonal transport and
      transcriptional regulation. The notion for an essential postnatal function of APP
      has been demonstrated genetically, as mice deficient in both APP and APLP2 or all
      three APP isoforms exhibit early postnatal lethality and neuroanatomical
      abnormalities. Recent findings have also brought to light two possible functions
      of the APP family in the brain-regulation of neural progenitor cell proliferation
      and axonal outgrowth after injury. Interestingly, these two apparently related
      neurogenic/neuroregenerative functions of APP involve two separate domains of the
      molecule.

PMID- 16406236
TI  - Macromolecular substrate affinity for free factor VIIa is independent of a buried
      protease domain N-terminus.
AB  - The initial recognition and binding of macromolecular substrates by factor VIIa
      (FVIIa) in complex with tissue factor has been shown to be mediated by areas
      distinct from the active site (so-called exosites). The present aim was to shed
      light on whether the N-terminal tail of the protease domain of FVIIa influences
      factor X (FX) binding, and whether the zymogen-like conformation of free FVIIa
      has a decreased affinity for FX compared to the active conformation. Two
      derivatives of FVIIa, one (FFR-FVIIa) with a stably buried N-terminus
      representing the active conformation of FVIIa and one (V154G-FVIIa) with a fully
      exposed N-terminus representing the zymogen-like conformation, were used as
      inhibitors of FVIIa-catalyzed FX activation. Their inhibitory capacities were
      very similar, with K(i) values not significantly different from the K(m) for FX.
      This indicates that the conformational state of the N-terminus does not affect FX
      binding or, alternatively, that the activation domain including the N-terminal
      insertion site is easily shifted to the stable conformation ensuing FX docking to
      the zymogen-like conformation. The net outcome is that FX binding to the zymogen
      like form of FVIIa does not appear to be impaired.

PMID- 16406237
TI  - Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and
      ionic mechanisms.
AB  - Resveratrol has been demonstrated to produce a variety of biological actions.
      Accumulating line of evidence supported the view that resveratrol may exert
      protective effect on the cardiovascular system. The aim of the study was to
      assess the antiarrhythmic profile as well as electrophysiological properties of
      resveratrol. We observe the antiarrhythmic effect of resveratrol on aconitine
      induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary
      ligation induced rat arrhythmia animal models. Resveratrol significantly and dose
      dependently increased the doses of aconitine and ouabain required to induce the
      arrhythmia indexes. In coronary ligation induced rat arrhythmia model,
      resveratrol shortened duration of arrhythmia, decreased incidence of ventricular
      tachycardia and mortality. Electrophysiological experiment revealed that
      resveratrol could shorten APD through inhibition of ICa and selective enhancement
      of IKs without an effect on IKr.

PMID- 16406238
TI  - Characterization of a rice (Oryza sativa L.) gene encoding a temperature
      dependent chloroplast omega-3 fatty acid desaturase.
AB  - A cDNA, designated Osfad8, encoding a chloroplast omega-3 fatty acid desaturase
      responsible for trienoic fatty acid formation, was isolated from the leaves of
      Oryza sativa L. by RT-PCR. Southern blot hybridization indicated that a small
      gene family composed of two copies or closely linked genes exists. RNA in situ
      hybridization showed that the accumulation of Osfad8 mRNA was abundant in leaves
      but hardly detectable in roots. The Osfad8 transcript level in leaves was much
      higher at 15 degrees C than at normal temperature (25 degrees C). In situ
      hybridization also showed particularly prominent expression of Osfad8 in the
      palisade layer and spongy parenchyma cells of leaves when exposed to 15 degrees C
      conditions for 5 days and 10 days. Two transgenic lines (8S-52 and 8S-101)
      harboring the Osfad8 ORF in sense orientation under the control of the CaMV 35S
      promoter contained increased levels of hexadecatrienoic (16:3) and linolenic
      (18:3) fatty acids. When exposed to 2 degrees C for 7 days, the damage observed
      to the control plants was significantly alleviated in the 8S-52 and 8S-101 lines.
      The amounts of trienoic fatty acids in an Osfad8 antisense line (8A-35) declined
      40.2% compared to the control plants. The 8A-35 plants survived after growth at
      44 degrees C for 3 days while the control plants died. These data suggest that
      Osfad8 encodes a temperature-dependent chloroplast omega-3 fatty acid desaturase.

PMID- 16406240
TI  - Involvement of spinal glia in tetanically sciatic stimulation-induced bilateral
      mechanical allodynia in rats.
AB  - The previous study showed involvement of spinal glia in tetanically sciatic
      stimulation-induced long-term potentiation (LTP) of C-fiber-evoked field
      potentials in the spinal dorsal horn. In the present study, the
      electrophysiological recording and paw withdrawal threshold (PWT) to von Frey
      stimulation were assessed following unilaterally tetanically sciatic stimulation
      in rats. Tetanic stimuli elicited LTP of both A- and C-fiber-evoked field
      potentials. After stimulation with the same parameter, bilateral PWTs to
      mechanical stimuli decreased. Intrathecal administration of fluorocitrate (1
      nmol/10 microl), an astrocyte inhibitor, partially inhibited tetanic stimulation
      induced reduction of bilateral PWTs. A similar effect also occurred at the
      contralateral side. And this bilateral inhibition of mechanical threshold lasted
      8 days. Similarly, intrathecal administration of d-amino acid oxygenase (50
      microg/mul, 10 microl), D-serine inhibitor, partially inhibited tetanic sciatic
      stimulation-induced reduction of bilateral PWTs for 24 h. The results showed that
      spinal glia plays an important role in bilaterally mechanical allodynia by
      tetanic sciatic stimulation of the sciatic nerve.

PMID- 16406239
TI  - Mutational analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in
      Tunisian patients with nonsyndromic hearing loss.
AB  - We explored the mitochondrial 12S rRNA and the tRNASer(UCN) genes in 100 Tunisian
      families affected with NSHL and in 100 control individuals. We identified the
      mitochondrial A1555G mutation in one out of these 100 families and not in the 100
      control individuals. Members of this family harbouring the A1555G mutation showed
      phenotypic heterogeneity which could be explained by an eventual nuclear
      mitochondrial interaction. So, we have screened three nuclear genes: GJB2, GJB3,
      and GJB6 but we have not found correlation between the phenotypic heterogeneity
      and variants detected in these genes. We explored also the entire mitochondrial
      12S rRNA and the tRNASer(UCN) genes. We detected five novel polymorphisms: T742C,
      T794A, A813G, C868T, and C954T, and 12 known polymorphisms in the mitochondrial
      12S rRNA gene. None of the 100 families or the 100 controls were found to carry
      mutations in the tRNASer(UCN) gene. We report here the first mutational screening
      of the mitochondrial 12S rRNA and the tRNASer(UCN) genes in the Tunisian
      population which describes the second family harbouring the A1555G mutation in
      Africa and reveals novel polymorphisms in the mitochondrial 12S rRNA gene.

PMID- 16406242
TI  - Current practice in the management of superficial bladder cancer in the
      Netherlands and Belgian Flanders: a survey.
AB  - OBJECTIVE: Because there is no national guideline for the diagnosis, therapy and
      follow up of (superficial) bladder cancer in the Netherlands and Belgium, the
      actual patient management may differ between urologists. The purpose of this
      study is to get insight in the current way urologists diagnose, treat and follow
      patients with superficial bladder cancer. METHODS: All practising urologists in
      the Netherlands (n = 293) and Flemish speaking Belgium (Flanders, n = 223)
      received a questionnaire with regard to the current management of patients with
      superficial bladder cancer. The results were compared with the guidelines
      provided by the European Association of Urology (EAU). Also a comparison was made
      between the two countries and between university and community hospitals.
      RESULTS: The results show a wide variation in current practice for superficial
      bladder cancer. Although the majority of urologists do not follow the EAU
      guidelines, current practice roughly matches these guidelines. There are no major
      differences between the two countries or between different types of hospitals.
      Discrepancies between current practice and guidelines are mostly too frequent use
      of techniques for the diagnosis, treatment and follow-up. CONCLUSION: In all,
      there is a need for clear guidelines in superficial bladder cancer and an
      effective implementation of such guidelines into everyday practice.

PMID- 16406241
TI  - Extracorporeal shock wave lithotripsy in the treatment of proximal ureteral
      stones: Does the presence and degree of hydronephrosis affect success?
AB  - OBJECTIVES: We investigated the relation between the presence and degree of stone
      induced hydronephrosis and the outcome of extracorporeal shock wave lithotripsy
      (SWL) in patients with solitary proximal ureteral stones. METHODS: 130 patients
      with or without hydronephrosis were treated with SWL. The degree of
      hydronephrosis was defined by renal ultrasound. Patients were divided into four
      groups according to the degree of stone induced hydronephrosis. Group 0 (24%) had
      no urinary system dilatation, group 1 (31.2%) had a mild dilatation of the renal
      pelvis, group 2 (40%) had a moderate and group 3 (4.8%) a severe dilatation of
      the renal pelvis and calices. The stone size, number of shock waves applied and
      number of sessions required to achieve stone clearance were recorded. RESULTS:
      Mean stone size was 8.2 mm+/-2.5 mm. Mean time to stone clearance was 13.7 days+/
      16.3. In 74.4% of patients stone clearance was observed. Additional 4.8% harbored
      residual fragments < or =3 mm after 3 months. Differences among the four groups
      in terms of stone size, time to stone clearance and treatment failure were not
      significant. CONCLUSIONS: The presence or degree of hydronephrosis caused by a
      proximal ureteral stone does not affect the time to stone clearance or success
      rate after SWL.

PMID- 16406243
TI  - An epidemiological study of primary nocturnal enuresis in Chinese children and
      adolescents.
AB  - AIMS: Assessment of the prevalence of primary nocturnal enuresis (PNE) and its
      risk factors in Chinese children and adolescents in the central areas of mainland
      China. METHODS: A cross-sectional study of PNE was performed by distributing
      11799 self-administered questionnaires to parents of 5-18-year-old students in 32
      schools of Henan province China. The questionnaire asked about sociodemographic
      data, PNE data, physical or psychological disorders, and family stressors. The
      PNE children were divided into a pediatric group (age 5-12) and an adolescent
      group (age 13-18). RESULTS: The response rate was 88% (10383/11799) in which
      10088 (85.5%) were qualified to enter the final statistical analysis. The overall
      prevalence of PNE was 4.07% (95%CI 3.68-4.46) and that of marked PNE was 1.46%
      (95%CI 1.23-1.69). PNE was significantly more in boys than in girls. The
      prevalence decreased with age without gender bias. Of all enuretic children,
      21.17% had daytime urinary symptoms and 22.87% had a positive family history.
      Only 6.08% of PNE had sought professional help. The episodic severity of PNE,
      associated daytime symptoms, positive family history, and seeking for
      professional help in adolescent group were significantly higher than those of
      pediatric group. Age, inhabitation (living in rural or urban areas), arousal
      dysfunction, associated daytime symptoms and family history were found to be
      significant predictors of marked PNE. Among PNE cases with a positive family
      history, there was no significant difference in the familial distribution between
      boys and girls. CONCLUSIONS: The prevalence of age-related PNE from Chinese
      school children is lower than those reported from western countries and other
      Asian countries. Age, inhabitation (rural or urban), arousal dysfunction,
      associated daytime symptom and family history are significant as predictors of
      marked PNE. The misconceptions among Chinese parents require health education
      intervention.

PMID- 16406244
TI  - Postload plasma glucose and 30-year mortality among nondiabetic middle-aged men
      from the general population: the ERFORT Study.
AB  - PURPOSE: The purpose of the study is to examine for the first time the
      association between 1-hour postload plasma glucose levels and known diabetes and
      30-year total mortality. METHODS: The population-based Erfurt Male Cohort Study
      of 1160 men aged 40 to 59 years was carried out between September 1973 and August
      1975. A 1-hour postload venous blood sample was obtained after an oral glucose
      tolerance test in all nondiabetic subjects. Mortality follow-up continued until
      death or September 30, 2003. RESULTS: Only 25 subjects were lost to follow-up,
      but 595 study participants (51.3%) died. Survival curves for persons with
      diabetes, subjects with postload glucose levels greater than 200 mg/dL, and those
      with not elevated levels already start to diverge after 2 years in persons with
      diabetes, but only after 5 years in subjects with high postload glucose levels.
      After 30 years of follow-up, men with diabetes had an almost twofold risk for
      death (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.26-2.97) and men
      with a postload plasma glucose level greater than 200 mg/dL had a 1.5-fold
      increased risk for death (HR, 1.49; 95% CI, 1.17-1.88) compared with men in the
      lower-glucose-level group, even after multivariable adjustment. CONCLUSIONS:
      Postload hyperglycemia is a long-term predictor for all-cause mortality in middle
      aged men without diabetes from the general population.

PMID- 16406245
TI  - Age trajectories of grip strength: cross-sectional and longitudinal data among
      8,342 Danes aged 46 to 102.
AB  - PURPOSE: The purpose is to study the age trajectory of hand-grip strength after
      the age of 45 years. METHODS: In this study, we use data from three large
      nationwide population-based surveys of Danes aged 45 to 102 years with a total of
      8342 participants with grip-strength measurements and up to 4 years of follow-up.
      Grip strength was measured by using a portable hand dynamometer. RESULTS: Grip
      strength declines throughout life for both males and females, but among the
      oldest women, the longitudinal curve reaches a horizontal plateau. The course of
      the decline is estimated by using full information in the longitudinal data and
      is found to be almost linear in the age span of 50 to 85 years. In this age span,
      mean annual grip-strength loss is estimated to be 0.59 (0.02) (SE) kg for men and
      0.31 (0.01) kg for women. CONCLUSION: This study confirms the previously reported
      grip-strength decline with increasing age. Estimates were obtained by using full
      information methods from large population-representative studies. Equations of
      expected grip strength, as well as tables with sex-, age-, and height-stratified
      reference data, provide an opportunity to include grip-strength measurement in
      clinical care in similar populations.

PMID- 16406246
TI  - Benzodiazepines and risk for breast cancer.
AB  - PURPOSE: The study aim is to evaluate benzodiazepine use and risk for breast
      cancer in Ontario, Canada, by using a population-based case-control study design.
      METHODS: Cases were a random sample of women aged 25 to 74 years identified
      through the Ontario Cancer Registry and diagnosed with breast cancer between 1996
      and 1998 (n = 3133). Controls were an age-matched random sample of women (n =
      3062). Cases and controls completed a self-administered questionnaire that
      included questions about their past use of benzodiazepines (defined as daily use
      for at least 2 months) and potential confounders. Individual classes of
      benzodiazepines also were evaluated. Multivariate logistic regression analysis
      was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were
      estimated. RESULTS: Compared with nonusers, ever use of benzodiazepines was not
      significantly associated with risk for breast cancer (OR, 1.06; 95% CI, 0.88
      1.27). No apparent trends were observed for duration of use, time since first
      use, or time since last use. Estimates according to individual classes of
      benzodiazepines, including diazepam, lorazepam, and chlordiazepoxide, also were
      not statistically significant. CONCLUSION: Our data show no association between
      benzodiazepine use and breast cancer risk. Results confirm findings from previous
      studies that diazepam use does not increase the risk for breast cancer and also
      suggest no association with the use of other benzodiazepine compounds.

PMID- 16406247
TI  - Dietary intake of seaweed and minerals and prevalence of allergic rhinitis in
      Japanese pregnant females: baseline data from the Osaka Maternal and Child Health
      Study.
AB  - PURPOSE: It may be worthwhile to assess the possible protective effect of the
      traditional Japanese diet on allergic disorders. This cross-sectional study
      investigated the relationship between dietary intake of seaweed, vegetables,
      fruit, antioxidants, fiber, and minerals and the prevalence of allergic rhinitis.
      METHODS: Study subjects were 1002 Japanese pregnant women. Allergic rhinitis
      (including cedar pollinosis) was defined as present if subjects had received drug
      treatment at some point during the previous 12 months. Information on dietary
      factors was collected by using a self-administered diet history questionnaire.
      RESULTS: Seaweed intake was associated independently with a decreased prevalence
      of allergic rhinitis. Significant inverse dose-response relationships were found
      between calcium and phosphorus intake and allergic rhinitis prevalence. There
      also was a tendency for an inverse association between magnesium consumption and
      allergic rhinitis. Additional adjustment for calcium or magnesium intake
      apparently did not influence the inverse association with seaweed consumption.
      Consumption of vegetables, fruit, vitamins C and E, fiber, and zinc showed no
      association with allergic rhinitis, whereas a significant positive relationship
      was observed between beta-carotene intake and allergic rhinitis. CONCLUSIONS:
      High dietary intake of seaweed, calcium, magnesium, and phosphorus may be
      associated with a decreased prevalence of allergic rhinitis.

PMID- 16406248
TI  - Social health insurance in a developing country: the case of the Philippines.
AB  - Very little is known about the Philippine health care system, and in particular
      its experience with social health insurance (SHI). Having initiated an SHI
      programme 35 years ago, the Philippines hold many lessons for the development of
      such schemes in other low and middle-income countries. We analyse the challenges
      currently facing PhilHealth, the national health insurer. PhilHealth was formed
      in 1995 as a successor to the Medicare programme and was given a mandate to
      achieve universal coverage by 2010. To date, PhilHealth has been quite successful
      in some areas (e.g. enrollment), but lags behind in others (e.g. quality and
      price control). We conclude that SHI in the Philippines has been a success story
      so far and provides lessons for countries in a similar situation. For example:
      (i) SHI is based on value decisions and the clear statement of societal goals can
      give guidance in the technical execution, (ii) SHI is a financing institution and
      needs to be treated accordingly, (iii) SHI can be implemented independently of
      the current economic situation and might actually contribute to economic
      development, (iv) community-based health care financing schemes should be merged
      with the national SHI in the long run, and (v) there is a strong need to push for
      high quality care and improved physical access. No clear suggestions can be given
      with respect to the benefit catalogue and the balance between economies of scale
      and decentralisation. Although riddled with many inadequacies, PhilHealth was set
      up as a strong and largely politically independent institution for the
      development of SHI. SHI can act as a stabilizing institution in a politically and
      economically volatile environment.

PMID- 16406250
TI  - Pharmacotherapy of depressed children and adolescents: current issues and
      potential directions.
AB  - The recent deliberations by the U.S. Food and Drug Administration (FDA) regarding
      the relationship between antidepressants and suicidality in children have incited
      debates about the safety of these medications for the treatment of pediatric
      depression. In light of these events, this review discusses four issues
      pertaining to pharmacotherapy for pediatric depression. First, we summarize
      pertinent data from randomized controlled trials of antidepressants for pediatric
      depression. These data provide strong support for fluoxetine and modest support
      for the other antidepressants. Second, we examine the outcome of the FDA meta
      analysis of the data on antidepressant-induced suicidality, with specific
      emphasis on the methodological limitations of this analysis. Third, we consider
      the collective implications of the antidepressant efficacy and suicidality data
      on clinical practice. Specifically, we present several compelling arguments that
      justify the continued use of antidepressants for pediatric depression, despite
      the inherent limitations of these medications. Finally, we review several
      pathophysiological factors that might provide insights into treatment response
      and impact the design of future pharmacotherapy studies of depression. These
      factors relate to diagnostic heterogeneity, developmental consistency, and
      psychobiology. Potentially novel pharmacotherapies are also discussed.

PMID- 16406249
TI  - Fornix integrity and hippocampal volume in male schizophrenic patients.
AB  - BACKGROUND: The hippocampus has been shown to be abnormal in schizophrenia. The
      fornix is one of the main fiber tracts connecting the hippocampus with other
      brain regions. Few studies have evaluated the fornix in schizophrenia, however. A
      focus on fornix abnormalities and their association with hippocampal
      abnormalities might figure importantly in our understanding of the
      pathophysiology of schizophrenia. METHODS: Line-scan diffusion tensor imaging
      (DTI) was used to evaluate diffusion in the fornix in 24 male patients with
      chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy
      (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter
      integrity, were generated to quantify diffusion within the fornix. We used high
      spatial resolution magnetic resonance imaging (MRI) to measure hippocampal
      volume. RESULTS: FA and cross-sectional area of the fornix were significantly
      reduced in patients compared with control subjects. D(m) was significantly
      increased, whereas hippocampal volume was bilaterally reduced in patients.
      Reduced hippocampal volume was correlated with increased mean D(m) and reduced
      cross-sectional area of the fornix for patients. Patients also showed a
      significant correlation between reduced scores on neuropsychologic measures of
      declarative-episodic memory and reduced hippocampal volumes. CONCLUSIONS: These
      findings demonstrate a disruption in fornix integrity in patients with
      schizophrenia.

PMID- 16406252
TI  - An RNA-centered view of eukaryotic cells.
AB  - Emerging evidence suggests that the introns and intergenic sequences of the
      genomes of higher eukaryotes (the "junk" DNA) codes for a vast, RNA-based,
      genetic regulatory network. It is believed that this network is responsible for
      the variety and complexity of terrestrial life. We conjecture that this
      regulatory network is more properly viewed as an RNA "community", composed of a
      rich and largely unexplored biochemical web of RNA interactions. Viewed as an RNA
      community, we hypothesize that the RNA regulatory network of higher eukaryotes
      can re-wire itself, and employ various and evolvable mutational strategies in
      response to external pressures. Thus, we argue that much evolutionary change is
      due to intracellular, RNA-mediated learning processes. Successful strategies and
      pathways are then recorded (hard-wired) into the DNA genome via reverse
      transcriptase. We present evidence, which is consistent with this viewpoint, and
      make specific theorems, which could be used to test the utility of our framework.
      If essentially correct, the RNA-community view of eukaryotic cells could
      reconcile measured point mutation and gene duplication rates with actual rates of
      evolutionary change. Futhermore, the RNA-community view of eukaryotic cells
      suggests that agent-based modeling techniques, used in mathematical economics,
      game theory, and neuroscience, will likely be as useful in understanding the
      functioning of eukaryotic cells as the pathway-based approaches of systems
      biology. We conclude this paper by arguing that a sufficient amount of biological
      knowledge has been accumulated to initiate a systematic program of experimental
      and computational studies of the origins and macroevolution of terrestrial life.

PMID- 16406251
TI  - Respiratory burst activity of Atlantic cod (Gadus morhua L.) blood phagocytes
      differs markedly from that of rainbow trout.
AB  - In the present study we investigated the respiratory burst (RB) activity of
      Atlantic cod (Gadus morhua L.) blood phagocytes and we evaluated how the RB
      activity of cod blood cells differ from that of trout. The RB activities were
      measured directly from highly diluted whole blood as luminol-amplified
      chemiluminescence (CL) under various conditions. Studies regarding the blood
      dilutions for cod whole blood chemiluminescence measurements (WBCL) revealed that
      at a final blood dilution of 1.5 microl ml(-1) or less the CL response was
      strictly proportional to the number of phagocytes. This range of blood dilution
      did not markedly differ from that of trout. However, the opsonisation capacity of
      cod plasma was markedly poorer. The RB activity of phagocytes was most active at
      15 degrees C when heterologous cod serum was used as a source of opsonin, whereas
      at final blood dilution of 8.0 microl ml(-1) (when homologous cod plasma was at a
      higher concentration) the highest RB activity was observed at 10 degrees C.
      Aeromonas salmonicida strain MT004 (As MT004) induced higher RB activity than the
      two known pathogens for cod, atypical A. salmonicida and Vibrio anguillarum. Cod
      blood phagocytes were more responsive to plastic surfaces and the adhesion
      response of phagocytes was partly inhibited but did not totally vanish even at a
      final gelatin concentration of 0.4%. Moreover, cod serum enhanced the adherence
      of phagocytes and cod blood phagocytes also showed slow spontaneous
      degranulation. Finally, within the tested anticoagulants (heparin, Na-citrate,
      EDTA) heparin treated blood phagocytes generated the highest RB activity.

PMID- 16406253
TI  - When language breaks into pieces. A conflict between communication through
      isolated signals and language.
AB  - Here, we study a communication model where signals associate to stimuli. The
      model assumes that signals follow Zipf's law and the exponent of the law depends
      on a balance between maximizing the information transfer and saving the cost of
      signal use. We study the effect of tuning that balance on the structure of signal
      stimulus associations. The model starts from two recent results. First, the
      exponent grows as the weight of information transfer increases. Second, a
      rudimentary form of language is obtained when the network of signal-stimulus
      associations is almost connected. Here, we show the existence of a sudden
      destruction of language once a critical balance is crossed. The model shows that
      maximizing the information transfer through isolated signals and language are in
      conflict. The model proposes a strong reason for not finding large exponents in
      complex communication systems: language is in danger. Besides, the findings
      suggest that human words may need to be ambiguous to keep language alive.
      Interestingly, the model predicts that large exponents should be associated to
      decreased synaptic density. It is not surprising that the largest exponents
      correspond to schizophrenic patients since, according to the spirit of Feinberg's
      hypothesis, i.e. decreased synaptic density may lead to schizophrenia. Our
      findings suggest that the exponent of Zipf's law is intimately related to
      language and that it could be used to detect anomalous structure and organization
      of the brain.

PMID- 16406254
TI  - Alpha 1-acid glycoprotein reverses cocaine-induced sodium channel blockade in
      cardiac myocytes.
AB  - Alpha 1-acid glycoprotein (AAG) is an acute phase protein capable of binding
      basic drugs. This action explains its reversal of sodium channel blockade by
      drugs such as amitriptyline and quinidine. We report here the reversal of cocaine
      induced sodium channel blockade by AAG. The sodium channel blocking property of
      cocaine is a major mechanism behind cocaine-induced sudden cardiac death, since
      sodium channels play a key role in the initiation and regulation of the heart
      beat. Voltage-gated sodium current (I(Na)) was recorded using whole-cell patch
      clamp techniques. Guinea-pig cardiac ventricular myocytes were isolated and
      continuously perfused at room temperature with physiological solutions. At
      concentrations ranging from 5 to 320 microM cocaine showed a dose-dependent and
      reversible blockade of I(Na) with an IC50 of 45.9 microM. The addition of
      equimolar amounts of AAG to cocaine produced almost complete reversal of
      cocaine's effects, suggesting a single binding site for cocaine on the AAG
      molecule. With changes of peak I(Na) normalized against control as 1, cocaine at
      20 and 40 microM reduced I(Na) to 0.62+/-0.042 (n = 6) and 0.57+/-0.052 (n = 9),
      respectively, and the addition of an equimolar concentration of AAG reversed
      I(Na) to 0.86+/-0.022 and 0.91+/-0.060, respectively. IN CONCLUSION: AAG reverses
      cocaine-induced sodium channel blockade in a dose-dependent manner, indicating a
      therapeutic potential to reverse acute cocaine cardiac toxicity.

PMID- 16406255
TI  - Effect of ethanol on human osteosarcoma cell proliferation, differentiation and
      mineralization.
AB  - The habitual consumption of even moderate quantities of alcoholic beverages is
      clearly associated with reduced bone mass, increased prevalence of skeletal
      fracture and also it is the major risk factor for the development of secondary
      osteoporosis. The present in vitro study was designed to determine the dose
      response effects of ethanol on osteoblast-like human osteosarcoma cells (SaOS-2)
      proliferation, differentiation, mineralization and cyto-toxicity. SaOS-2 cells
      were plated in 48 and 6 well culture plates and exposed to different
      concentrations of ethanol (1, 10, 100, 200 and 300 mM) for 24, 48 and 72 h. At
      the end of incubation, proliferation of cells was studied using crystal violet
      Bioassay. The cell lysate was utilized to determine ALP activity and conditioned
      media were used to measure LDH activity. Histochemical localization of ALP and
      mineralized nodules were studied from cells treated with ethanol (10 and 100 mM)
      for 21 days. At higher doses, there was a significant reduction in cell number,
      whereas at lower doses there were variable effects. In 24 h treatment, the higher
      doses showed a significant increase in ALP activity, whereas 48 and 72 h
      treatments showed an opposite trend. Ethanol treatment caused a dose- and time
      dependent increase in LDH activity. Ethanol treatment altered the quality of
      mineralization at 10 mM dose whereas completely inhibited mineralization at 100
      mM dose, despite the presence of serum. In conclusion, the toxic effect of
      ethanol is reflected on cell proliferation, differentiation and mineralization
      even at low doses and at extended treatment duration.

PMID- 16406256
TI  - Distributed BOLD-response in association cortex vector state space predicts
      reaction time during selective attention.
AB  - Human cortical information processing is thought to be dominated by distributed
      activity in vector state space (Churchland, P.S., Sejnowski, T.J., 1992. The
      Computational Brain. MIT Press, Cambridge.). In principle, it should be possible
      to quantify distributed brain activation with independent component analysis
      (ICA) through vector-based decomposition, i.e., through a separation of a mixture
      of sources. Using event-related functional magnetic resonance imaging (fMRI)
      during a selective attention-requiring task (visual oddball), we explored how the
      number of independent components within activated cortical areas is related to
      reaction time. Prior to ICA, the activated cortical areas were determined on the
      basis of a General linear model (GLM) voxel-by-voxel analysis of the target
      stimuli (checkerboard reversal). Two activated cortical areas (temporoparietal
      cortex, medial prefrontal cortex) were further investigated as these cortical
      regions are known to be the sites of simultaneously active electromagnetic
      generators which give rise to the compound event-related potential P300 during
      oddball task conditions. We found that the number of independent components more
      strongly predicted reaction time than the overall level of "activation" (GLM BOLD
      response) in the left temporoparietal area whereas in the medial prefrontal
      cortex both ICA and GLM predicted reaction time equally well. Comparable
      correlations were not seen when principle components were used instead of
      independent components. These results indicate that the number of independently
      activated components, i.e., a high level of cortical activation complexity in
      cortical vector state space, may index particularly efficient information
      processing during selective attention-requiring tasks. To our best knowledge,
      this is the first report describing a potential relationship between neuronal
      generators of cognitive processes, the associated electrophysiological evidence
      for the existence of distributed networks and BOLD fMRI signals using information
      from model order selection techniques.

PMID- 16406258
TI  - Increased water diffusivity in the frontal and temporal cortices of schizophrenic
      patients.
AB  - Schizophrenia has been suggested to be the result of both macroscopic and
      microscopic abnormalities in the brain. Although no definitive clinico
      pathological correlations have been found to reconcile the many facets inherent
      in this disorder, the recent development of the magnetic resonance diffusion
      tensor imaging (DTI) has allowed us to gather useful information regarding the
      microcircuitry of the brain. Specifically, the apparent diffusion coefficient
      (ADC) reflects the degree of diffusion barriers and heterosynaptic communication
      for the brain neurotransmitter. Nineteen patients with DSM-IV schizophrenia and
      21 age- and sex-matched control subjects participated in DTI, and the severity of
      the patients' symptoms was evaluated according to the Positive and Negative
      Syndrome Scale (PANSS). The ADC values were determined and compared between
      patients and control subjects via voxel-based morphometry. The results show an
      increased ADC in the bilateral fronto-temporal regions of the schizophrenic
      patients, as compared with those of the control subjects. In addition, the ADC
      values in the area of the right insular were correlated with the negative
      syndromes from the PANSS. Our findings of increased water diffusivity in the
      fronto-temporal regions of schizophrenic patients and the correlation between
      negative symptom scales and the ADC in the right insular region indicate that
      damaged brain microcircuitry might contribute to the pathophysiology of
      schizophrenia. These findings contribute towards integrating micro and
      macrostructural abnormalities and syndromes of schizophrenia.

PMID- 16406257
TI  - Neural circuits involved in imitation and perspective-taking.
AB  - Is it important to adopt the perspective of the model when learning a new skill?
      Is the "mirror system" equally involved when the teacher is facing or side-by
      side with students? In this functional MRI study, we measured the cerebral
      hemodynamic changes in participants who watched video-clips depicting simple hand
      or foot actions. The participants either watched passively or imitated these
      actions. Half the video-clips depicted actions filmed from the perspective of the
      participant (1st-person perspective) and half from a frontal view as if watching
      someone else (3rd-person perspective). Behavioral results showed that latency to
      imitate was significantly shorter for the 1st-person perspective than the 3rd
      person perspective. Functional imaging results demonstrate that the observation
      of intransitive actions engaged primary visual and extrastriate visual areas, but
      not the premotor cortex. Imitation vs. observation of actions yielded enhanced
      signal in the contralateral somatosensory and motor cortices, cerebellum, left
      inferior parietal lobule and superior parietal cortex, and left ventral premotor
      cortex. Activity in the lateral occipital cortex around the extrastriate body
      area was significantly enhanced during imitation, as compared to observation of
      actions confirming that this region involvement reaches beyond the perception of
      body parts. Moreover, comparisons of the two visual perspectives showed more
      activity in the left sensory-motor cortex for 1st-person, even during observation
      alone, and in the lingual gyrus for 3rd-person perspective. These findings
      suggest that the 1st-person perspective is more tightly coupled to the sensory
      motor system than the 3rd-person perspective, which requires additional
      visuospatial transformation.

PMID- 16406259
TI  - A candidate juvenoid hormone receptor cis-element in the Daphnia magna hb2
      hemoglobin gene promoter.
AB  - Hemoglobin levels are significantly elevated in the crustacean Daphnia magna by
      juvenoid hormones. The present study was undertaken to identify the specific
      globin (hb) genes that are induced by juvenoids and to identify putative juvenoid
      response elements (JREs) that may mediate this induction. Gene product of globin
      2 (hb2), but not globin 1 and globin 3, was robustly elevated following juvenoid
      treatment of daphnids. A candidate JRE, located in the promoter of hb2, bound
      activated factor(s) in response to juvenoid treatment of daphnids. This hormone
      induced protein:JRE interaction was robust when daphnids were reared at high
      oxygen tension but was inhibited when daphnids were reared under low pO2,
      implying that hypoxia might act to disrupt juvenoid-mediated endocrine signaling.
      The candidate JRE consists of a steroid/retinoid-response element-like core
      adjacent to a 5' AT-rich extension and thus bears resemblance to response
      elements that bind monomeric nuclear receptors. The induction of hb2 mRNA levels
      by juvenoid treatment occurred rapidly (within 4 h of exposure) and was not
      attenuated by treatment of daphnids with cycloheximide. In contrast,
      cycloheximide treatment did block hormone-mediated elevations in hemoglobin
      protein levels. Thus, induction of hb2 by juvenoids was not dependent upon the
      synthesis of secondary transcription factors that bound the JRE but was likely
      due to activation of the gene directly by the juvenoid-receptor complex. Affinity
      pull-down experiments with nuclear proteins extracted from juvenoid-treated
      daphnids using the JRE as bait yielded a 52kDa candidate for a monomeric nuclear
      receptor in D. magna that may mediate the regulatory activity of juvenoids.

PMID- 16406260
TI  - The essential role of glucocorticoids for proper human osteoblast differentiation
      and matrix mineralization.
AB  - Glucocorticoids (GCs) exert profound effects on bone and are essential for human
      osteoblast differentiation. However, GCs are still interpreted as negative
      regulators of bone formation, mainly caused by the detrimental effects on bone
      after clinical use of GCs. In this paper we emphasize the importance of GCs for
      proper human osteoblast differentiation and matrix mineralization. We show that
      human osteoblast differentiation needs to be triggered by GCs in a specific time
      window during the early stages of development. Exposure to GCs in the beginning
      of osteoblast development induces a dose dependent increase in alkaline
      phosphatase activity and matrix mineralization. GC-induced differentiation
      stimulated expression of genes involved in bone formation and suppressed genes
      that negatively regulate bone formation and mineralization. Furthermore we
      highlight the importance of local cortisol activation in osteoblasts by
      expression of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1).

PMID- 16406261
TI  - Aromatase and estrogen receptors in male reproduction.
AB  - Aromatase is a terminal enzyme which transforms irreversibly androgens into
      estrogens and it is present in the endoplasmic reticulum of numerous tissues. We
      have demonstrated that mature rat germ cells express a functional aromatase with
      a production of estrogens equivalent to that of Leydig cells. In humans in
      addition to Leydig cells, we have shown the presence of aromatase in ejaculated
      spermatozoa and in immature germ cells. In most tissues, high affinity estrogen
      receptors, ERalpha and/or ERbeta, mediate the role of estrogens. Indeed, in human
      spermatozoa, we have successfully amplified ERbeta mRNA but the protein was not
      detectable. Using ERalpha antibody we have detected two proteins in human
      immature germ cells: one at the expected size 66 kDa and another at 46 kDa likely
      corresponding to the ERalpha isoform lacking exon 1. In spermatozoa only the 46
      kDa isoform was present, and we suggest that it may be located on the membrane.
      In addition, in men genetically deficient in aromatase, it is reported that
      alterations of spermatogenesis occur both in terms of the number and motility of
      spermatozoa. All together, these observations suggest that endogenous estrogens
      are important in male reproduction.

PMID- 16406262
TI  - A novel post-transcriptional mechanism of regulation of luteinizing hormone
      receptor expression by an RNA binding protein from the ovary.
AB  - Luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor, a member of
      the rhodopsin/beta(2) adrenergic receptor subfamily of G-protein coupled
      receptors, is expressed primarily in the gonads and essential for the regulation
      of reproductive function. In the ovary, the expression of the receptor is post
      transcriptionally regulated under physiological conditions. Studies from our
      laboratory showed that the ligand-induced down-regulation of the receptor occurs
      by accelerated degradation of the mRNA rather than by decreased transcription. We
      have identified a cytoplasmic LHR mRNA binding protein (LRBP) as a trans-acting
      factor in regulating LHR mRNA levels. LRBP binds to the coding region of LHR mRNA
      and causes accelerated degradation of mRNA. The RNA binding activity of LRBP was
      found to be inversely correlated to LH/hCG receptor mRNA levels. LRBP was
      purified to homogeneity and its identity was established as mevalonate kinase by
      N-terminal microsequencing and MALDI analysis. Mevalonate kinase, an enzyme
      involved in de novo synthesis of cholesterol, belongs to the GHMP family of
      kinases having a potential RNA binding fold. The expression of MVK mRNA and MVK
      protein levels were induced in response to hCG treatment prior to the down
      regulation of LH/hCG receptor mRNA expression. A model for the post
      transcriptional regulation of LH/hCG receptor in the ovary by mevalonate kinase
      is proposed.

PMID- 16406263
TI  - 17Beta-hydroxysteroid dehydrogenases in human endometrium and its disorders.
AB  - In situ estrogen metabolism and synthesis have been considered to play a very
      important role in the development and progression of human endometrial carcinoma.
      17Beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes involved in the
      formation of active sex steroids, including testosterone, estrone (E1) and
      estradiol (E2). Estrogens are interchanged by two enzymes, 17-HSD types 1 and 2,
      type 1 converts E1 to E2, and type 2 does reverse actions. 17-HSD type 5
      catalyzes the reduction of androstenedione to testosterone. 17-HSD type 2
      expression was decreased through normal endometrium, hyperplasia and carcinoma
      accordingly. There was a significant inverse correlation between intratumoral E2
      concentration and the level of 17-HSD type 2 mRNA in endometrial carcinoma. 17
      HSD type 5 expression was significantly increased through normal endometrium,
      hyperplasia and carcinoma accordingly. These results indicated that 17-HSD types
      2 and 5 play an important role in the regulation of in situ estrogen production
      in endometrial carcinoma.

PMID- 16406264
TI  - Control of cell proliferation by steroids: the role of 17HSDs.
AB  - Sex steroid hormone signaling regulates the development, growth, and functioning
      of the breast and the prostate and plays a role in the development and
      progression of cancer in these organs. The intracellular concentration of active
      sex steroid hormones in target tissues is regulated by several enzymes, including
      17beta-hydroxysteroid dehydrogenases (17HSDs). Changes in the expression patterns
      of these enzymes may play a pathophysiological role in malignant transformation.
      We recently analyzed the mRNA expressions of the 17HSD type 1, 2, and 5 enzymes
      in about 800 breast carcinoma specimens. Both 17HSD type 1 and 2 mRNAs were
      detected in normal breast tissue from premenopausal women but not in specimens
      from postmenopausal women. The patients with tumors expressing 17HSD type 1 mRNA
      or protein had significantly shorter overall and disease-free survival than the
      other patients. The expression of 17HSD type 5 was significantly higher in breast
      tumor specimens than in normal tissue. Cox multivariate analyses showed that
      17HSD type 1, tumor size, and estrogen receptor alpha (ERalpha) had independent
      prognostic significance. We developed, using a LNCaP prostate cancer cell line, a
      model to study the malignant transformation of prostate cancer and showed that
      androgen-sensitive LNCaP cells are transformed into neuroendocrine-like cells
      when cultured without androgens and, eventually into highly proliferating
      androgen-independent cells. We conducted Northern hybridizations and microarrays
      to analyze the gene expression during these processes. Substantial changes in the
      expressions of steroid metabolizing enzymes occurred during the transformation
      process. The variations in steroid-metabolizing enzymes during cancer progression
      may be crucial in the regulation of the growth and function of organs.

PMID- 16406265
TI  - Alterations in glucose homeostasis in SSTR1 gene-ablated mice.
AB  - SSTR1 is found on the majority of human pancreatic beta cells, however, its role
      in insulin secretion has yet to be elucidated. In this study, we used the SSTR1
      knockout mouse model to examine the role of SSTR1 in insulin secretion and
      glucose homeostasis in mice. Despite the reported effect of SSTR1 in inhibiting
      growth hormone secretion, SSTR1-/- mice had significantly reduced body weight
      with growth retardation. Perfusion of isolated mouse pancreata at 3 months of age
      demonstrated a significant increase in insulin secretion in SSTR1-/- mice
      compared with that of WT controls. We also found that at 3 months of age, SSTR1-/
      mice had significantly decreased levels of systemic insulin secretion and were
      glucose intolerant. However, SSTR1 gene-ablated mice had a much higher rate of
      insulin clearance compared to WT mice at the same age. When challenged at 12
      months of age, we found SSTR1-/- mice had increased glucose tolerance with
      exaggerated increase of insulin levels at the end of the experiment.
      Immunochemical analysis showed that the pancreatic islets of SSTR1-/- mice had
      significantly decreased levels of somatostatin staining and a significant
      decrease of SSTR5 expression. These results demonstrate that SSTR1 plays an
      important role in the regulation of insulin secretion in the endocrine pancreas
      in mice.

PMID- 16406266
TI  - Regulation of FSH receptor, PKIbeta, IL-6 and calcium mobilization: Possible
      mediators of differential action of FSH.
AB  - Sertoli cells support the development of germ cells by providing a
      microenvironment in the seminiferous tubules. FSH stimulates Sertoli cell
      proliferation only during neonatal period till day 18 in the immature rat whereas
      FSH regulates only functional parameters in the adult rat Sertoli cells. This
      suggests that FSH exerts differential action in immature and adult Sertoli cells.
      In an attempt to elucidate the mechanism by which FSH exerts the differential
      effects, we have carried out both in vivo and in vitro studies using Sertoli
      cells isolated from immature (7-10 days old) and adult (90 days old) rats. The
      differential role of FSH was studied at the receptor as well as at the signaling
      level. Monitoring the level of expression of FSH receptor by RTPCR and northern
      blot analysis revealed that the expression was more in immature Sertoli cells.
      Furthermore, it was found that FSH up (1.8-fold) regulates its receptor level
      only in the immature Sertoli cells and not in the adult. Results also revealed
      that PKIbeta and calcium, which are the downstream signaling molecules, are
      involved in FSH regulated Sertoli cells proliferation. It was also observed that
      FSH up (1.4-fold) regulates the levels of expression of IL-6 mRNA only in the
      immature rat Sertoli cells suggesting the possibility of its involvement in FSH
      regulated Sertoli cell proliferation.

PMID- 16406267
TI  - Expression of steroid hormone receptors, proliferation and apoptotic markers in
      primate endometrium.
AB  - In humans, circulating levels of steroid hormones vary during the menstrual
      cycle, with oestrogen elevated in the proliferative phase and progesterone
      increased during the secretory phase. In humans, oestrogen levels also increased
      during the mid-secretory phase, but this is not observed in non-human primates.
      In marmosets, the New World monkeys, plasma oestrogen and progesterone levels
      exhibit similar profiles as those found in Old World monkeys, however, these
      animals do not menstruate. Proliferative and apoptotic changes occur at specific
      phases of the menstrual cycle, suggesting regulation by steroid hormones. It was,
      therefore, of interest to compare expression of steroid hormone receptors,
      proliferation and apoptotic markers in the uterine endometrium of marmosets and
      humans. Localization of oestrogen receptor-alpha (ER-alpha) was observed in
      glandular epithelial cells during the proliferative phase in marmosets and in
      human endometria. A decrease in ER-alpha and progesterone receptor (PR-A) was
      observed during the mid luteal phase in both species although a postovulatory
      oestradiol peak is observed in human but not in marmoset. A decrease in PR-A in
      the late secretory phase was seen in marmoset as well as in human endometria. The
      proliferation marker PCNA was enhanced in the proliferative phase in both
      species, but it was increased in late secretory phase only in marmosets.
      Apoptosis as revealed by a TUNEL assay was moderate in early stage in both
      species. Surprisingly, apoptosis, as well as the localization of the pro
      apoptotic Bcl-2 family member, Bax, was optimal in marmosets during the mid
      secretory phase when plasma progesterone levels were high. On the other hand, in
      the human, apoptosis was maximal by TUNEL assay in late secretory phase, but Bax
      protein was highest in the mid-secretory phase. Thus, Bax may be initiating
      apoptosis in the endometrial glands as well as in the stroma. Although the
      pattern of steroid receptor expression in endometria of marmosets and humans are
      similar, proliferation and apoptosis markers appear to be regulated by other
      factors along with steroid hormones.

PMID- 16406268
TI  - The relation between psychological factors and DNA-damage: a critical review.
AB  - Investigating relations between psychological factors and DNA-damage can
      contribute to understanding how psychological factors affect the etiology and
      prognosis of relevant diseases (e.g., cancer, heart disease) at the fundamental
      level of mutated cells. This article critically reviews 21 studies in animals and
      humans testing relations between psychological factors and DNA-damage. After
      providing a biological background, we critically review each study. The findings
      in humans are mapped onto a model of stress, coping and health. These studies
      demonstrate causal relations between acute stressors and DNA-damage in animals
      and significant correlations between psychological factors (e.g., depression,
      coping) and DNA-damage in humans, which are moderated by gender. Possible
      mechanisms for these relations, limitations of studies, clinical implications and
      suggestions for future research are provided.

PMID- 16406269
TI  - Immunohistochemical analysis of histone H3 acetylation and methylation--evidence
      for altered epigenetic signaling following traumatic brain injury in immature
      rats.
AB  - Posttranslational modifications (PTMs) of histone proteins may result in altered
      epigenetic signaling after pediatric traumatic brain injury (TBI). Hippocampal
      histone H3 acetylation and methylation in immature rats after moderate TBI were
      measured and decreased only in CA3 at 6 h and 24 h with persistent methylation
      decreases up to 72 h after injury. Decreased histone H3 acetylation and
      methylation suggest altered hippocampal CA3 epigenetic signaling during the first
      hours to days after TBI.

PMID- 16406270
TI  - Imidaprilat, an angiotensin-converting enzyme inhibitor exerts neuroprotective
      effect via decreasing dopamine efflux and hydroxyl radical generation induced by
      bisphenol A and MPP+ in rat striatum.
AB  - The present study examined the ability of antioxidant effects of angiotensin
      converting enzyme (ACE) inhibitor, imidaprilat, on the synergistic effect of
      bisphenol A and 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical
      (*OH) formation and dopamine (DA) efflux in extracellular fluid of rat striatum.
      Bisphenol A clearly enhanced OH formation and DA efflux induced by MPP(+). When
      imidaprilat was infused in bisphenol A and MPP(+)-treated rats, DA efflux and OH
      formation significantly decreased, as compared with that in the bisphenol A and
      MPP(+) treated control. These results suggest that ACE inhibitors may protect
      against the synergistic effect of bisphenol A and MPP(+)-induced OH formation via
      suppressing DA efflux in the rat striatum.

PMID- 16406271
TI  - Influences of carotenoid supplementation on the integrated antioxidant system of
      a free living endangered passerine, the hihi (Notiomystis cincta).
AB  - The integrated antioxidant system is recognised as an essential component of an
      organisms self maintenance. Our knowledge of this system, however, is largely
      restricted to species of economic importance. The health and productivity
      benefits these dietary based compounds provide make them increasingly relevant
      for study in wildlife ecology. The aim of this research was to identify numerous
      components of this integrated system in a free living and endangered passerine
      bird, the hihi. In addition experimental supplementation with carotenoids was
      used to investigate the modulatory interactions with other members of the
      antioxidant system. Our results identified lutein and zeaxanthin as the
      carotenoids utilised by hihi (82% and 17% of total carotenoids respectively in
      control samples of egg yolk, 84% and 16% of total carotenoids respectively in
      control samples of nestling plasma), and that vitamin E was represented by both
      alpha- and gamma-tocopherol. Retinol was also present, as was selenium in
      surprisingly high concentrations (599.64, 91.76, 377.72 ng/g fresh weight Se in
      control samples of yolk, albumin and plasma, respectively). Supplementation of
      lutein and zeaxanthin not only increased their presence in egg yolk
      (F(1,10)=14.285, P=0.005 and F(1,10)=9.606, P=0.015, respectively) and nestling
      plasma (F(1,19)=35.126, P<0.001 and F(1,19)=28.597, P<0001, respectively) but
      also led to increased selenium concentration in egg yolk (F(1,10)=7.213,
      P=0.028), increased retinol concentration in nestling plasma (F(1,19)=4.272,
      P=0.054) and decreased alpha-tocopherol concentration in nestling plasma
      (F(1,19)=5.122, P=0.037). These results provide detail of the antioxidant system
      in novel taxa and importantly highlight interaction between these various
      compounds. Given their increased application in productivity and health in
      agriculture and human medicine we highlight the potential application of this
      knowledge in wildlife ecology and conservation.

PMID- 16406272
TI  - Effect of long and short photoperiod on vasotocin neurons of paraventricular
      nuclei and adrenal function of water deprived Japanese quail.
AB  - The responses of magnocellular neurons of paraventricular nuclei (PVN) and
      changes to adrenal activity to water deprivation in Japanese quail maintained
      under gonado-inhibitory and stimulatory photoperiods were examined. Water
      deprivation of 4 days resulted in a 12% decrease in body weight of sexually
      regressed short day (SD, 6L:18D) quail, while the decrease was more (18%) in
      sexually stimulated long day (LD, 16L:8D) quail. The increase in plasma
      osmolality following water deprivation was also more (47%) in LD than to SD quail
      (36%). Under the LD condition, quail had increased numbers, sizes and
      immunostaining of ir-AVT neurons of PVN compared to SD condition. A significant
      increase in the number of ir-AVT neurons was observed following 4 days of water
      deprivation in both SD and LD quail compared to their respective fully hydrated
      controls. However, the degree of response was more under the LD compared to the
      SD condition suggesting that gonado-stimulatory long days increase the
      activity/response of the AVT system. Increased adrenal ascorbic acid content
      (i.e., activity) was also observed to quail of LD when compared to SD treatment.
      However, osmotic stress led to adrenal hypertrophy and hyperactivity of quail of
      both of the photoperiodic regimes. Our findings indicate that not only osmotic
      stress but also photo-gonadal stimulation upregulates the expression of
      hypothalamic AVT genes and increases the localization of ir-AVT in many neurons
      of PVN. The above results support the existence of a parallel adrenal-gonad
      relationship and increase in adrenal function during osmotic stress, which also
      leads to simultaneous increase in AVT system. We conclude that photo-sexual
      conditions alter hypothalamic vasotocinergic and adrenal activity in Japanese
      quail and the degree of stimulation of the two systems following osmotic stress
      is higher under gonado-stimulatory LD conditions.

PMID- 16406273
TI  - Effect of pethidine administered during the first stage of labor on the acid-base
      status at birth.
AB  - OBJECTIVE: To evaluate the association between the use of pethidine during the
      first stage of labor and the presence, type and timing of acidosis in the newborn
      at birth. STUDY DESIGN: Secondary data analysis of a randomized controlled trial,
      which included term singleton pregnancies diagnosed with dystocia and requiring
      active management of labor. Women were randomized to receive either 100 mg of
      pethidine or placebo. Statistical analyses were performed using chi(2) or
      Fisher's exact tests for proportions and multiple linear regression for
      continuous outcomes. RESULTS: Three hundred and eighty-three pregnant women with
      a valid arterial blood cord sample were included in the final analysis. Lower pH
      and bicarbonate levels, as well as higher pCO(2) levels were found in the
      pethidide group. A higher incidence of acidosis was found in the pethidine group
      (pH<7.12 OR: 8.59 95% C.I. 3.29, 22.46). The highest frequency of acidosis was
      encountered when pethidine-delivery interval was 5 h. CONCLUSION: Pethidine use
      during the first stage of labor was associated with an increased risk of acidosis
      at birth.

PMID- 16406275
TI  - In vivo determination of Neisseria meningitidis serogroup A capsular
      polysaccharide by whole cell high-resolution magic angle spinning NMR
      spectroscopy.
AB  - High resolution-magic angle spinning (HRMAS) NMR spectroscopy was applied to
      serogroup A Neisseria meningitidis (NMA) to determine precise structures of
      capsular polysaccharide (CPS) expressed on the meningococcal surface. Both the O
      acetylated (OAc) NMA parent and a mynC::aphA3 OAc- mutant demonstrated
      characteristic CPS-derived NMR signals indicating cell-surface expression of CPS,
      but only the parent expressed O-3 and O-4 acetylation signals. A capsule
      defective strain showed no NMR signals for CPS. The (1)H NMR HRMAS spectral
      patterns correlated with the purified CPS (1)H NMR profiles. HRMAS NMR can
      distinguish detailed complex carbohydrate structures expressed on bacteria. NMA
      express both O-3 and O-4 acetylated polymers but not in equimolar ratio amounts
      in vivo.

PMID- 16406276
TI  - H2BC: a new technique for NMR analysis of complex carbohydrates.
AB  - It is demonstrated that the H2BC NMR pulse sequence (J. Am. Chem. Soc.2005, 127,
      6154, Magn. Reson. Chem.2005, 43, 971-974) offers unambiguous assignments and
      significant simplification of NMR spectra of large and complex carbohydrates
      compared to other techniques for the establishment of correlations over more than
      one bond. H2BC almost exclusively correlates protons and proton-bearing carbon
      spins separated by two covalent bonds and is independent of occasionally
      vanishing (2)J(CH) coupling constants, which alleviates the problem of missing
      two-bond correlations in HMBC spectra. H2BC also solves the problem of
      distinguishing two- and three-bond correlations in HSQC-TOCSY or HMBC. It is a
      further asset of H2BC that the experiment is significantly shorter than HMBC and
      HSQC-TOCSY, and hence less sensitive to transverse relaxation. The H2BC
      experiment is demonstrated on an approximately 30-residue oligosaccharide from
      Francisella victoria.

PMID- 16406278
TI  - A novel carbonic anhydrase from the mantle of the pearl oyster (Pinctada fucata).
AB  - A novel carbonic anhydrase (CA) has been purified from the mantle of the pearl
      oyster, Pinctada fucata, by ammonium sulfate precipitation and affinity
      chromatography. Its molecular mass was determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) to be approximately 38 kDa. Native
      PAGE shows that the novel CA can bind a fluorescent probe, 5-dimethylamino-1
      naphthalenesulfonamide (DNSA), known to specifically bind carbonic anhydrase.
      Compared to carbonic anhydrase I (CAI) from human erythrocytes, the novel CA
      migrates faster indicating that it is more acidic. The effect of an inhibitor on
      the enzyme activity was also examined. The CA from the mantle showed a weak
      resistance to acetazolamide (AZ), a specific inhibitor of CA. When DNSA was bound
      to CA, it caused the wavelength of emission maximum intensity to blue shift to
      454 nm upon excitation at 326 nm. Histochemical data indicates that the enzyme is
      distributed widely throughout the mantle tissue, being concentrated at the edge
      of the mantle. The evidence presented indicates a function for CA in the process
      of pearl formation and biomineralization.

PMID- 16406277
TI  - Isolation and structural characterization of an immunostimulating polysaccharide
      from fuzi, Aconitum carmichaeli.
AB  - A water-soluble polysaccharide named as FPS-1 was isolated from fuzi, the root of
      Aconitum carmichaeli Debx. by hot-water extraction, anion-exchange and gel
      permeation chromatography and tested for its pharmacological activities. Its
      structural characteristics were investigated by FTIR, HPLC, NMR spectroscopy,
      methylation analysis and GLC-MS. Based on the data obtained, FPS-1 was determined
      to be an alpha-(1-->6)-d-glucan, with a weight-average molecular weight of about
      14,000Da. The glucan is highly branched with a single glucose at the C-3 position
      every four residues, on average, along the main chain. In immunopharmacological
      studies, FPS-1 showed potent stimulating effects on murine lymphocyte
      proliferation induced by concanavalin A or lipopolysaccharide both in vitro and
      in vivo as well as on splenocyte antibody production.

PMID- 16406279
TI  - 11Beta-hydroxysteroid dehydrogenase type 1--a role in inflammation?
AB  - Glucocorticoids are widely used for their potent anti-inflammatory effects.
      Endogenous glucocorticoids are immunomodulatory and shape both adaptive and
      innate immune responses. Over the past decade, it has become apparent that an
      important level of control over endogenous glucocorticoid action is exerted by
      the 11beta-hydroxysteroid dehydrogenase enzymes. The type 1 enzyme, 11beta-HSD1,
      reduces inert glucocorticoids into active forms, thereby increasing intracellular
      ligand availability to receptors. Although 11beta-HSD1 activity has been shown to
      play an important role in the metabolic actions of glucocorticoids, its role in
      the immune response has, until recently, remained unclear. Here we review recent
      evidence pertaining to the role of 11beta-HSD1 in the inflammatory response.

PMID- 16406280
TI  - 11Beta-hydroxysteroid dehydrogenases in human endometrium.
AB  - Key reproductive events, such as menstruation and implantation, are considered to
      be inflammatory processes and glucocorticoids act as anti-inflammatory agents.
      The balance of expression of types 1 and 2 11beta-hydroxysteroid dehydrogenases
      (11betaHSD) controls the availability of cortisol to bind to the glucocorticoid
      receptor (GR) and mineralocorticoid receptor (MR). Expression profiles of
      glucocorticoid-metabolising enzymes and their cognate receptors have been
      characterized in the reproductive tract. We propose that factors that
      peripherally promote glucocorticoid action are part of an anti-inflammatory
      response to tissue remodelling in human endometrium. Protein and mRNA expression
      in endometrium were investigated using immunohistochemistry and quantitative real
      time PCR. There was up-regulated expression of 11betaHSD-1 at menstruation and in
      first trimester decidua. 11BetaHSD-2 and GR were expressed across the cycle. The
      MR expression pattern across the cycle and in decidua implies progesterone may
      also play a regulatory role. The precise roles and interactions of these proteins
      require further investigation.

PMID- 16406281
TI  - Progesterone resistance in endometriosis: link to failure to metabolize
      estradiol.
AB  - Endometriosis is the most common cause of pelvic pain and affects an estimated 5
      million women in the US. The biologically active estrogen estradiol (E2) is the
      best-defined mitogen for the growth and inflammation processes in the ectopic
      endometriotic tissue that commonly resides on the pelvic organs. Progesterone and
      progestins may relieve pain by limiting growth and inflammation in endometriosis
      but a portion of patients with endometriosis and pelvic pain do not respond to
      treatment with progestins. Moreover, progesterone-induced molecular changes in
      the eutopic (intrauterine) endometrial tissue of women with endometriosis are
      either blunted or undetectable. These in vivo observations are indicative of
      resistance to progesterone action in endometriosis. The molecular basis of
      progesterone resistance in endometriosis may be related to an overall reduction
      in the levels of progesterone receptors (PRs) and the lack of the PR isoform
      named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on
      stromal cells to induce secretion of paracrine factor(s). These unknown factor(s)
      act on neighboring epithelial cells to induce the expression of the enzyme 17beta
      hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes the
      biologically active estrogen E2 to estrone (E1). In endometriotic tissue,
      progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect
      in stromal cells. The inability of endometriotic stromal cells to produce
      progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to
      the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed
      in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in
      endometriosis giving rise to high local concentrations of this local mitogen. The
      cellular and molecular mechanisms underlying progesterone resistance and failure
      to metabolize E2 in endometriosis are reviewed.

PMID- 16406282
TI  - Bioinformatic identification and characterization of new members of short-chain
      dehydrogenase/reductase superfamily.
AB  - With about 60 genes known in the human genome, short-chain
      dehydrogenases/reductases (SDRs) form a large gene family with important
      implications for medicine. They are known to be involved in carcinogenesis (e.g.
      breast and prostate cancer) as well as in metabolic and degenerative defects such
      as the pathogenesis of Alzheimer's disease, osteoporosis and diabetes.
      Uncharacterized SDRs are thus potential candidates for many monogenic and
      multifactorial human diseases. The identification and functional analysis of such
      SDR enzymes is therefore the primary goal of the study leading to new targets for
      drug development. In all taxa (bacteria, plants, insects, vertebrates), members
      of SDR superfamily are known. Up to now, there are several thousand members
      annotated many of which have not been characterized biochemically with regard to
      enzymatic activity, substrate specificity, or subcellular localization. We
      bioinformatically identified 250 vertebrate candidate genes belonging to the SDR
      superfamily using the BioNetWorks software SDR finder. The number was reduced to
      95 after continuative analysis, including manual SDR motif verification and focus
      on human, rat and murine enzymes. Here, we present several new mammalian SDRs
      that were clustered into several enzymatically different groups by detailed
      phylogenetic analyses. Furthermore, characteristic mRNA expression patterns were
      identified for some of these genes by a recently developed in silico Northern
      blot method supporting their putative functions in retinoid, steroid, sugar and
      other metabolic pathways.

PMID- 16406283
TI  - In silico Northern blot, an automated method to determine expression patterns
      from EST databases, reveals tissue specificity of murine 17beta-hydroxysteroid
      dehydrogenase type 11.
AB  - In this study, we developed an automated in silico Northern blot (ISNB) for
      analysis of gene expression patterns from EST databases. This kind of analysis
      can facilitate initial enzyme characterization by providing tissue distribution
      patterns. For proof of principle, we analyzed the expression pattern of well
      characterized murine 17beta-hydroxysteroid dehydrogenases type 1 and 4. Less
      characterized murine 17beta-hydroxysteroid dehydrogenase type 11 (Dhrs 8) also
      was included and processed bioinformatically (ISNB) and further analyzed by
      Northern blot. The 17beta-hydroxysteroid dehydrogenase type 11 showed the same
      wide expression pattern by in silico and by wet laboratory approaches. The data
      point to its involvement of the enzyme in lipid metabolism. The quality of the
      ISNB relies on the quality of EST-databases. However, our approach is an easy and
      versatile tool of potentially universal application.

PMID- 16406284
TI  - Evaluation of inhibitors for 17beta-hydroxysteroid dehydrogenase type 1 in vivo
      in immunodeficient mice inoculated with MCF-7 cells stably expressing the
      recombinant human enzyme.
AB  - 17Beta-hydroxysteroid dehydrogenase (17HSD1) is an enzyme activating estrone (E1)
      to estradiol (E2). In the present study, a mechanistic animal model was set up
      for evaluating putative inhibitors for the human enzyme in vivo. Estrogen
      dependent MCF-7 human breast carcinoma cells were stably transfected with a
      plasmid expressing human 17HSD1. These cells formed estrogen-dependent tumors in
      immunodeficient mice. In the optimized model, tumor sizes were decreased in both
      ovariectomized and intact vehicle-treated mice, whereas they were maintained or
      slightly increased in mice supplemented 2 weeks with an appropriate dose of the
      17HSD1-substrate E1. Tumor sizes in mice treated with 0.1 micromol/kg/d of E1
      were reduced by administering 5 micromol/kg/d of different 17HSD1-inhibitors and
      a 86% reduction in size was detected with the most potent inhibitor. A dose
      response relationship in the inhibitory effect of this compound further confirmed
      the validity of the model for testing the drug candidates in vivo.

PMID- 16406285
TI  - Inhibitory effects of fluorine-substituted estrogens on the activity of 17beta
      hydroxysteroid dehydrogenases.
AB  - In search for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1
      (h17beta-HSD1) a specific group of steroids with interesting properties including
      novel compounds was investigated. Several estratriene derivatives with fluorine
      substitution in position 17 of the steroidal scaffold were synthesised and tested
      in vitro towards recombinant h17beta-HSD1, 2, 4, 5 and 7. Moderate, mostly
      unselective inhibitors of h17beta-HSD1 and h17beta-HSD2 and a selective inhibitor
      of h17beta-HSD5 were identified. The structure-activity relationship with respect
      to inhibitory strengths and selectivity of these compounds on five h17beta-HSDs
      is discussed.

PMID- 16406286
TI  - Performance of low pH biofilters treating a paint solvent mixture: continuous and
      intermittent loading.
AB  - Two biofilters packed with a reticulated polyurethane foam medium were inoculated
      with a compost-derived enrichment culture grown under acidic conditions (pH 3.0)
      and then operated over a period lasting 63 days. Both biofilters were supplied
      with a humidified gas stream containing a five-component mixture of acetone,
      methyl ethyl ketone, toluene, ethylbenzene, and p-xylene at a total VOC loading
      rate 80.3 gm(-3)h(-1) to simulate treatment of air emissions resulting from
      manufacture of reformulated paint. One biofilter was operated under continuous
      loading conditions and the other received intermittent loading with contaminants
      supplied only 8 h/day. Nutrient solution with pH 3.0 was supplied approximately
      once per week to provide nitrogen and other nutrients. Data are presented which
      demonstrate that undefined mixed cultures acclimated at low pH can successfully
      treat paint solvent mixtures in biofilters. The biofilter receiving continuous
      loading reached high overall removal efficiency (greater than 90% overall
      removal) 3 weeks after startup, and performance increased over time reaching
      overall removal in the range of 97-99% after 50 days. Performance of the
      intermittently loaded biofilter developed more slowly, requiring 6 weeks to
      stabilize at an overall removal efficiency in excess of 90%. In both biofilters,
      ketone components were more rapidly degraded than aromatic components, and
      removal of aromatic compounds was somewhat unstable even after 2 months of
      biofilter operation. Scanning electron microscopy (SEM) revealed that fungi
      dominated the microbial populations in both biofilters.

PMID- 16406287
TI  - Equilibrium and thermodynamic parameters of single and binary mixture biosorption
      of lead (II) and copper (II) ions onto Pseudomonas putida: effect of temperature.
AB  - The biosorption of lead (II) and copper (II) ions, single component and binary
      systems, by dried P. putida was investigated in a batch system. The effects of
      initial pH, temperature, initial single and binary mixture concentrations on the
      biosorption kinetics and equilibrium uptake of each component, both single and
      binary mixtures were investigated. The bacterial biomass exhibited the highest
      single and binary lead (II) and copper (II) ions uptake capacity at 25 and 30
      degrees C, respectively, the initial pH value of 5.5 and at the initial metal
      ions concentration of 100 mg dm(-3). The Freundlich and Langmuir adsorption
      models were used for the mathematical description of the biosorption equilibrium
      and isotherm constants were evaluated at different temperatures. Adsorption data
      were well described by the Langmuir model, although they could be modeled by the
      Freundlich equation. The thermodynamics constants of the adsorption process:
      DeltaH degrees , DeltaS degrees and DeltaG degrees were evaluated. The results
      showed that biosorption of single and binary lead (II) ions on P. putida were
      exothermic and spontaneous. While biosorption of single and binary copper (II)
      ions on P. putida was endothermic and spontaneous.

PMID- 16406289
TI  - An alternative to Portland Cement for waste encapsulation--the calcium
      sulfoaluminate cement system.
AB  - Currently, Portland Cement (PC) is used extensively in the
      solidification/stabilisation of a wide variety of wastes. In the nuclear
      industry, low and intermediate level radioactive wastes are encapsulated or
      immobilised within composite PC cement systems based on high replacement with
      blast furnace slag or fly ash. However, the high alkalinity of these PC-based
      systems will corrode reactive metals found in some wastes releasing hydrogen and
      forming expansive corrosion products. Alternative cement systems could provide a
      different hydration chemistry, which would allow wastes containing these metals
      to be encapsulated with lower reactivity. Calcium sulfoaluminate (CS A) cement is
      one such cement. It combines economy of cost and low emission of CO(2) with rapid
      strength gain and compatibility with other construction materials. Hydration
      provides an internal pore solution where the pH is considerably lower than that
      of PC. The main hydration product, ettringite, can incorporate a number of ions
      into its crystal structure, making it an ideal candidate for waste
      immobilisation. This paper details some results from a commercial CS A system
      that examines aspects of mixing, hydration of different formulations and
      aluminium corrosion behaviour. The fluidity of mixes can be adjusted by changing
      the formulations. All designed mixes were set within 24 h with little bleeding
      and the pH values were in the range of 10-11.5. In addition, a significant
      reduction in Al corrosion was observed compared to a composite OPC system.
      Although these results provide encouragement for the idea that CS A cement can
      provide a possible alternative to PC in the immobilisation of difficult and
      reactive wastes, further investigation is needed.

PMID- 16406290
TI  - Leaching of chromated copper arsenate (CCA)-treated wood in a simulated monofill
      and its potential impacts to landfill leachate.
AB  - The proper end-of-life management of chromated copper arsenate (CCA)-treated
      wood, which contains arsenic, copper, and chromium, is a concern to the solid
      waste management community. Landfills are often the final repository of this
      waste stream, and the impacts of CCA preservative metals on leachate quality are
      not well understood. Monofills are a type of landfill designed and operated to
      dispose a single waste type, such as ash, tires, mining waste, or wood. The
      feasibility of managing CCA-treated wood in monofills was examined using a
      simulated landfill (a leaching lysimeter) that contained a mix of new and
      weathered CCA-treated wood. The liquid to solid ratio (LS) reached in the
      experiment was 0.63:1. Arsenic, chromium, and copper leached from the lysimeter
      at average concentrations of 42 mg/L for arsenic, 9.4 mg/L for chromium, and 2.4
      mg/L for copper. Complementary batch leaching studies using deionized water were
      performed on similar CCA-treated wood samples at LS of 5:1 and 10:1. When results
      from the lysimeter were compared to the batch test results, copper and chromium
      leachability appeared to be reduced in the lysimeter disposal environment. Of the
      three metals, arsenic leached to the greatest extent and was found to have the
      best correlation between the batch and the lysimeter experiments.

PMID- 16406292
TI  - Nitrate reductase gene involvement in hexachlorobiphenyl dechlorination by
      Phanerochaete chrysosporium.
AB  - Polychlorobiphenyl (PCB) degradation usually occurs through reductive
      dechlorination under anaerobic conditions and phenolic ring cleavage under
      aerobic conditions. In this paper, we provide evidence of nitrate reductase (NaR)
      mediated dechlorination of hexachlorobiphenyl (PCB-153) in Phanerochaete
      chrysosporium under non-ligninolytic condition and the gene involved. The NaR
      enzyme and its cofactor, molybdenum (Mo), were found to mediate reductive
      dechlorination of PCBs even in aerobic condition. Tungsten (W), a competitive
      inhibitor of this enzyme, was found to suppress this dechlorination. Chlorine
      release assay provided further evidence of this nitrate reductase mediated
      dechlorination. Commercially available pure NaR enzyme from Aspergillus was used
      to confirm these results. Through homology search using TBLASTN program, NaR gene
      was identified, primers were designed and the RT-PCR product was sequenced. The
      NaR gene was then annotated in the P. chrysosporium genome (GenBank accession no.
      AY700576). This is the first report regarding the presence of nitrate reductase
      gene in this fungus with the explanation why this fungus can dechlorinate PCBs
      even in aerobic condition. These fungal inoculums are used commercially as
      pellets in sawdust for enhanced bioremediation of PCBs at the risk of depleting
      soil nitrates. Hence, the addition of nitrates to the pellets will reduce this
      risk as well as enhance its activity.

PMID- 16406293
TI  - Distribution of polychlorinated biphenyls in the Newark Bay Estuary.
AB  - As part of the NJ Toxics Reduction Workplan for NY/NJ Harbor, ambient water
      samples were collected at 15 locations along the tidal portions of the
      Hackensack, Passaic, Raritan, Rahway and Elizabeth Rivers, and in Newark Bay, the
      Arthur Kill, and Kill van Kull. A Trace Organics Platform Sampler was used to
      collect a total of 73 dissolved phase and 73 suspended sediment phase samples
      between June 2000 and May 2002. These samples were analyzed for spatial and wet
      versus dry weather trends in the 114 polychlorinated biphenyls (PCBs; modified
      USEPA Method 1668A). Mean total PCB concentrations at the sampling locations
      ranged between 3.45 and 56 ng/L. PCB homolog groups distribution patterns at the
      sampling locations are presented.

PMID- 16406291
TI  - Photochemical mineralization of di-n-butyl phthalate with H2O2/Fe3+.
AB  - This study evaluated the performance of photo-Fenton reaction initiated by the UV
      irradiation with H(2)O(2)/Fe(3+), denoted as UV/H(2)O(2)/Fe(3+), to decompose di
      n-butyl phthalate (DBP) in the aqueous solution. The concentration of total
      organic carbon (TOC) was chosen as a mineralization index of the decomposition of
      DBP by the UV/H(2)O(2)/Fe(3+) process. A second-order kinetic model with respect
      to TOC was adequately adopted to represent the mineralization of DBP by the
      UV/H(2)O(2)/Fe(3+) process. The experimental results of this study suggested that
      the dosages with 4.74 x 10(-5) mol min(-1)L(-1) H(2)O(2) and initial Fe(3+)
      loading concentration of 4.50 x 10(-4) mol L(-1) in the solution at pH 3.0 with
      120 microW cm(-2) UV (312 nm) provided the optimal operation conditions for the
      mineralization of DBP (5 mg L(-1)) yielding a 92.4% mineralization efficiency at
      90 min reaction time.

PMID- 16406294
TI  - Use of a transient model to simulate fluidized bed incineration of sewage sludge.
AB  - This paper presents a mathematical model dedicated to fluidized bed incineration
      of sludge. The main assumptions as well as the principal equations of the model
      are presented. Basically, this model relies on instantaneous pyrolysis of sludge
      and on a five zones description of the hydrodynamics into the incinerator. Its
      originality is essentially due to the introduction of a two-dimensional buffer
      zone between the bubble and the emulsion phase. The chemistry of the gaseous
      system is described by chemical equilibrium. Results of a start up procedure have
      been presented in order to illustrate the ability of the model to describe
      transient behavior. To validate the model from an energetic point of view,
      different types of sludge (primary, activated and digested) have been computed
      and compared to industrial data and to results obtained from a simple
      calculation. The lower dryness limit corresponds to self incineration of the
      sludge. The higher one corresponds to maximal thermal level that should not be
      exceeded within the furnace.

PMID- 16406295
TI  - Recycling of agricultural solid waste, coir pith: removal of anions, heavy
      metals, organics and dyes from water by adsorption onto ZnCl2 activated coir pith
      carbon.
AB  - The abundant lignocellulosic agricultural waste, coir pith is used to develop
      ZnCl(2) activated carbon and applied to the removal of toxic anions, heavy
      metals, organic compounds and dyes from water. Sorption of inorganic anions such
      as nitrate, thiocyanate, selenite, chromium(VI), vanadium(V), sulfate, molybdate,
      phosphate and heavy metals such as nickel(II) and mercury(II) has been studied.
      Removal of organics such as resorcinol, 4-nitrophenol, catechol, bisphenol A, 2
      aminophenol, quinol, O-cresol, phenol and 2-chlorophenol has also been
      investigated. Uptake of acidic dyes such as acid brilliant blue, acid violet,
      basic dyes such as methylene blue, rhodamine B, direct dyes such as direct red
      12B, congo red and reactive dyes such as procion red, procion orange were also
      examined to assess the possible use of the adsorbent for the treatment of
      contaminated ground water. Favorable conditions for maximum removal of all
      adsorbates at the adsorbate concentration of 20 mg/L were used. Results show that
      ZnCl(2) activated coir pith carbon is effective for the removal of toxic
      pollutants from water.

PMID- 16406296
TI  - Photocatalytic decolorization and degradation of dye solutions and wastewaters in
      the presence of titanium dioxide.
AB  - In this study, the photocatalytic degradation of two commercial azo dyes in the
      presence of TiO(2) suspensions as photocatalyst has been investigated. The
      degradation of the dyes follows a pseudo-first-order kinetics according to the
      Langmuir-Hinshelwood model. Under the certain experimental conditions, in the
      presence of TiO(2) P-25 decolorization is achieved within 100 min of
      illumination, while in the presence of TiO(2) Hombikat UV-100 complete color
      disappearance is accomplished in less than 50 min of light exposure. The
      influence of various parameters, such as the type and mass of the catalyst, the
      initial concentration of the dye, etc. on the degradation process was examined.
      The mineralization of organic carbon was also evaluated by measuring the
      dissolved organic carbon (DOC) of the dye solutions. Moreover, the toxic
      properties of the dye solutions treated by photocatalysis were examined by the
      use of a Microtox bioassay (Vibrio fischeri). Finally, experiments using real
      textile wastewater were also carried out, in order to examine the effectiveness
      of the method to a more complex substrate.

PMID- 16406297
TI  - Biological treatment of wastewaters from a dye manufacturing company using a
      trickling filter.
AB  - The aim of this work was to assess the effectiveness of a biological trickling
      filter for the treatment of wastewaters produced by a company manufacturing
      organic dyes and varnishes. The combined wastewater effluent was fed to a pilot
      scale trickling filter in two feeding modes, continuously and as a sequencing
      batch reactor (SBR). The biodegradability of the diluted wastewaters that were
      subjected to physicochemical treatment, using Ca(OH)(2) and FeSO(4), was
      initially studied using a continuously operated trickling filter. The system
      efficiency ranged up to 60-70% for a hydraulic loading of 1.1 m(3)/m(2)day and up
      to 80-85% for a hydraulic loading 0.6 m(3)/m(2)day. A stable chemical oxygen
      demand (COD) removal efficiency of 60-70% was achieved even in the case of
      undiluted wastewater at a hydraulic loading of 1.1 m(3)/m(2)day. The
      effectiveness of biological treatment of a mixture of the company's main
      wastewater streams was also examined. The microorganisms developed in the
      trickling filter were able to efficiently remove COD levels up to 36,000 mg/L,
      under aerobic conditions at pH values between 5.5 and 8.0. Depending on the
      operating conditions of the system, about 30-60% of the total COD removal was
      attributed to air stripping caused by the air supply at the bottom of the filter,
      whereas the rest of the COD was clearly removed through biological action. The
      proposed biological treatment process based on a trickling filter, which was
      operated either continuously or even better in an SBR mode, appears as a
      promising pretreatment step for coping with dye manufacturing wastewaters in
      terms of removing a significant portion of the organic content.

PMID- 16406298
TI  - Leaching characteristics of slag from the melting treatment of municipal solid
      waste incinerator ash.
AB  - This study investigated the composition and leaching characteristics of municipal
      solid waste incinerator (MSWI) ash and slag. The modified slags were
      characterized after the melting of MSWI ash mixtures at 1400 degrees C for 30
      min. The ash mixtures were composed of different types of MSWI ash, including
      cyclone ash, scrubber ash and bottom ash, in various proportions. The results
      indicate that the Cd leaching concentration of the cyclone ash and the Pb
      leaching concentration of the scrubber ash reached 1.82 and 8.7 mg/L,
      respectively, which exceeds the ROC EPA's current regulatory thresholds, and can
      thus be classified as hazardous. The results of the analysis of the metal content
      and the leaching behavior of heavy metals, showed high concentrations of Cu and
      Zn, but a low leaching ratio of these metals. Concerning the characteristics of
      the modified slags, the X-ray diffraction patterns of the MSWI fly ash slag
      showed that it contained large amounts of glass. The toxicity characteristic
      leaching procedure (TCLP) leaching concentrations of the target metals of all the
      slags, met the ROC EPA's regulatory thresholds. The leaching concentrations of
      heavy metals in the F- and B1-slag were lower than those in the cyclone and the
      bottom ash, because there was a high amount of SiO(2), which formed a net-like
      structure in the bottom ash.

PMID- 16406299
TI  - Detection of a known mutation M412T in the LDL receptor in a Chinese Thai FH
      family.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant
      hypercholesterolemia caused by mutation in the LDL receptor gene. M412T mutation
      of the LDL receptor gene was previously observed in a single female patient
      diagnosed as having primary hypercholesterolemia. However, the analysis was
      incomplete and there was no confirmation of the M412T as the FH-causing mutation.
      We identified a mutation in the LDL receptor gene that underlines the severe FH
      phenotype in a new case, a female Chinese Thai patient. METHODS: Identification
      was made by PCR-SSCP, direct DNA sequencing and confirmed by allele specific
      amplification (ASA) originally designed for this current study. RESULTS: The
      entire LDL receptor gene screening revealed the genetic alteration that also
      caused M412T mutation in this new index patient. ASA analysis confirmed the DNA
      sequence in this patient and further identified three family members as M412T
      carriers. CONCLUSIONS: The finding of this mutation in 2 apparently unrelated
      index patients and the co-segregation of M412T and FH phenotype in the family of
      the present index case should provide evidence and confirm that the M412T was
      likely to be a disease-causing mutation. Whether M412T is common either as a
      founder or recurrent mutation among FH Chinese Thai population is unknown at
      present and remains to be clarified.

PMID- 16406301
TI  - Why are plastid genomes retained in non-photosynthetic organisms?
AB  - The evolution of the plastid from a photosynthetic bacterial endosymbiont
      involved a dramatic reduction in the complexity of the plastid genome, with many
      genes either discarded or transferred to the nucleus of the eukaryotic host.
      However, this evolutionary process has not gone to completion and a subset of
      genes remains in all plastids examined to date. The various hypotheses put
      forward to explain the retention of the plastid genome have tended to focus on
      the need for photosynthetic organisms to retain a genetic system in the
      chloroplast, and they fail to explain why heterotrophic plants and algae, and the
      apicomplexan parasites all retain a genome in their non-photosynthetic plastids.
      Here we consider two additional explanations: the 'essential tRNAs' hypothesis
      and the 'transfer-window' hypothesis.

PMID- 16406300
TI  - Serum insulin-like growth factor-axis and matrix metalloproteinases in patients
      with rheumatic arthritis or rheumatic heart disease.
AB  - BACKGROUND: Insulin-like growth factor (IGF)-I plays an important role for
      maintaining cardiac functions. We clarified the unknown role of IGF-axis in
      rheumatic heart disease (RHD). METHOD: Interleukin (IL)-10, growth hormone (GH),
      IGF, IGF binding protein (IGFBP)-3 and matrix metalloproteinase (MMP) were
      measured by ELISA and zymography in 30 age range-matched normal subjects
      (control), 36 patients with acute phase of rheumatoid arthritis (RA) with
      positive rheumatoid factor (RF) and C-reactive protein (CRP), and in 43 patients
      with RHD with negative RF and CRP. RESULT: Compared with normal subjects,
      increased IL-10 level and decreased GH were found in RA group whereas unchanged
      IL-10 and decreased GH were found in RHD group. Compared with age range-matched
      normal subjects, decreased IGFBP-3, MMP-9 levels, unchanged IGF-I were found in
      RA group whereas decreased IGF-I levels, unchanged IGFBP3 and increased MMP-9 at
      age>30 years were found in RHD group. IGF-II was not changed in RA and RHD
      groups. CONCLUSION: These findings may imply that during inflammatory phase, the
      levels of anti-inflammation was high and total IGF-I and IGF bioavailability were
      maintained in patients with RA. Our findings in RHD may speculate that the long
      term reduction of GH and IGF-I as well as the compensating effects of upregulated
      MMP-9 activity may be partially involved in the long-term pathogenesis from RHD
      to heart failure. Decreased GH, decreased IGF-I and increased MMP-9 activities
      may be possible diagnostic markers in RHD for developing heart failure.

PMID- 16406302
TI  - The problem of how fungal and oomycete avirulence proteins enter plant cells.
AB  - Recent advances in cloning avirulence genes from a rust fungus and three oomycete
      species have provided the novel insight that these eukaryotic plant pathogens
      deliver small proteins into the host cell cytoplasm where they are recognized by
      resistance proteins. Anne Rehmany et al. have recently identified a potential
      host-targeting signal in oomycete avirulence proteins from Hyaloperonospora
      parasitica, Phytophthora sojae and Phytophthora infestans that might be involved
      in transporting proteins into the host cell. This signal is surprisingly similar
      to the host targeting signal used by the malaria pathogen Plasmodium fulciparum
      to target virulence proteins to the mammalian host cell.

PMID- 16406303
TI  - Polygalacturonase inhibiting proteins: players in plant innate immunity?
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are extracellular leucine-rich
      repeat (LRR) proteins that recognize and inhibit fungal polygalacturonases (PGs).
      The PG-PGIP interaction favours the accumulation of elicitor-active
      oligogalacturonides and causes the activation of defence responses. Small gene
      families encode PGIP isoforms that differ in affinity and specificity for PGs
      secreted by different pathogens. The consensus motif within the LRR structure of
      PGIPs is the same as that of the extracellular receptors of the plant innate
      immune system. Structural and functional evidence suggest that PGIPs are
      versatile proteins involved in innate immunity and that they are capable of
      recognizing different surface motifs of functionally related but structurally
      variable PGs.

PMID- 16406304
TI  - Harvesting the potential of induced biological diversity.
AB  - For most of the past century, chemical and physical mutagens have been used in
      plant genetic research to introduce novel genetic variation. In crop improvement,
      more than 2000 plant varieties that contain induced mutations have been released
      for cultivation having faced none of the regulatory restrictions imposed on
      genetically modified material. In plant science, mutational approaches have found
      extensive use in forward genetics and for enhancer and suppressor screens -
      particularly in model organisms where positional cloning is easily achieved.
      However, new approaches that combine mutagenesis with novel and sensitive methods
      to detect induced DNA sequence variation are establishing a new niche for
      mutagenesis in the expanding area of (crop) plant functional genomics and
      providing a bridge that links discovery in models to application in crops.

PMID- 16406305
TI  - Functions of amine oxidases in plant development and defence.
AB  - Copper amine oxidases and flavin-containing amine oxidases catalyse the oxidative
      de-amination of polyamines, which are ubiquitous compounds essential for cell
      growth and proliferation. Far from being only a means of degrading cellular
      polyamines and, thus, contributing to polyamine homeostasis, amine oxidases
      participate in important physiological processes through their reaction products.
      In plants, the production of hydrogen peroxide (H(2)O(2)) deriving from polyamine
      oxidation has been correlated with cell wall maturation and lignification during
      development as well as with wound-healing and cell wall reinforcement during
      pathogen invasion. As a signal molecule, H(2)O(2) derived from polyamine
      oxidation mediates cell death, the hypersensitive response and the expression of
      defence genes. Furthermore, aminoaldehydes and 1,3-diaminopropane from polyamine
      oxidation are involved in secondary metabolite synthesis and abiotic stress
      tolerance.

PMID- 16406306
TI  - Glucosinolate metabolism and its control.
AB  - Glucosinolates and their associated degradation products have long been
      recognized for their distinctive benefits to human nutrition and plant defense.
      Because most of the structural genes of glucosinolate metabolism have been
      identified and functionally characterized in Arabidopsis thaliana, current
      research increasingly focuses on questions related to the regulation of
      glucosinolate synthesis, distribution and degradation as well as to the
      feasibility of engineering customized glucosinolate profiles. Here, we highlight
      recent progress in glucosinolate research, with particular emphasis on the
      biosynthetic pathway and its metabolic relationships to auxin homeostasis. We
      further discuss emerging insight into the signaling networks and regulatory
      proteins that control glucosinolate accumulation during plant development and in
      response to environmental challenge.

PMID- 16406307
TI  - The multiple sclerosis trait and the development of multiple sclerosis: genetic
      vulnerability and environmental effect.
AB  - The remarkably low rate of concordance of multiple sclerosis (MS) in monozygotic
      twins has never been fully explained but it implies the possibility of a systemic
      condition called the multiple sclerosis trait (MST), which is quite different
      from asymptomatic MS. It results from the action of an antigenic challenge on the
      immune system of a genetically vulnerable person that does not cause damage to
      the nervous parenchyma; it may never evolve into the disease MS. A subsequent
      environmental viral-antigenic event in some MST-carriers can change the trait
      into the disease. This event could be an infection, which need not be
      symptomatic, or a vaccination. The MS may become symptomatic, remain
      asymptomatic, or manifested only by lesions visible by MRI. It is likely that the
      development of the MST, called activation, occurs early in life, while the
      transition from MST to MS, called acquisition, takes place at puberty in most
      patients. Differences in prevalence between pre-puberal migrants, and the locally
      born children of migrants, and their population of origin may also be explained
      by the MST.

PMID- 16406308
TI  - Acute mobile phone effects on pre-attentive operation.
AB  - There is a debate whether electromagnetic field (EMF) emitted by mobile phones
      (MP) have an effect on cognitive functions. Since the auditory P50 component of
      event-related potentials (ERPs) reflects pre-attentive processing and working
      memory (WM) operation, the present study was designed to investigate whether the
      exposure to MP-EMF affects the patterns of the P50 component of ERPs elicited
      during a WM test. The P50 elicited during a WM task and evoked by two warning
      stimuli low and high frequency (500 and 3000 Hz) has been assessed in 19 normal
      subjects (10 women and 9 men) both without and with exposure to a 900 MHz signal,
      emitted by a dipole antenna placed near the subjects. Results showed that the
      presence of MP-EMFs induced statistically significant increase in the amplitude
      of P50 evoked by the low frequency stimuli, at Fp1 and O1 electrode leads as
      compared to themselves without MP-EMF exposure. In contrast the exposure to MP
      EMFs revealed statistically significant decrease of the amplitude of P50 evoked
      by the high frequency stimuli, at Fp1 electrode lead as compared to themselves
      without MP-EMF exposure. These findings provide evidence that the MP-EMF emitted
      by mobile phone affect pre-attentive information processing as it is reflected in
      P50 evoked potential. The basis of such an effect is unclear, although several
      possibilities exist and call for potential directions of future research.

PMID- 16406309
TI  - Acetyl-L-carnitine prevents and reduces paclitaxel-induced painful peripheral
      neuropathy.
AB  - This study examines the potential efficacy of acetyl-L-carnitine (ALC) to prevent
      and treat paclitaxel-induced pain. Rats received four intraperitoneal (i.p.)
      injections of 2 mg/kg paclitaxel on alternate days which, following a short delay
      induced marked mechanical hypersensitivity. Daily administration of ALC (50 mg/kg
      and 100 mg/kg; p.o.; concurrently with paclitaxel and for 14 days afterwards)
      prevented the development of paclitaxel-induced pain. This effect was long
      lasting, for at least 3 weeks after the last dose of ALC. In a separate
      experiment, daily administration of ALC (100 mg/kg; p.o.; for 10 days) to rats
      with established paclitaxel-induced pain produced an analgesic effect. This
      effect dissipated shortly after ALC treatment was withdrawn. We conclude that ALC
      may be useful in the prevention and treatment of chemotherapy-induced painful
      peripheral neuropathy.

PMID- 16406311
TI  - Microinjection of prostaglandin E2 and muscimol into the preoptic area in
      conscious rats: comparison of effects on plasma adrenocorticotrophic hormone
      (ACTH), body temperature, locomotor activity, and cardiovascular function.
AB  - The preoptic area (POA) is thought to play an important role in thermoregulation
      and fever. Local application of prostaglandin E2 (PGE2) to this region elicits
      increases in core body temperature, heart rate, and plasma levels of
      adrenocorticotrophic hormone (ACTH). Similar effects on body temperature and
      heart rate have also been reported after local application of the GABAA receptor
      agonist muscimol to the preoptic area. The purpose of this study was to assess
      and compare the effects of microinjection of PGE2 and muscimol into the preoptic
      area in the same chronically instrumented conscious rats on plasma levels of
      ACTH. Injection of either PGE2 (150 pmol/100 nL) or muscimol (20 or 80 pmol/100
      nL) into the same sites in the preoptic area evoked increases in body
      temperature, heart rate, blood pressure, and plasma levels of ACTH, while
      significant increases in locomotor activity were apparent only after muscimol.
      These data confirm and extend previous findings and support the notion that
      neurons in the region of the preoptic area exert tonic inhibition on downstream
      mechanisms capable of increasing the activity of the hypothalamic-pituitary
      adrenal (HPA) axis as well as sympathetic thermogenic and cardiac activity.

PMID- 16406310
TI  - Central but not peripheral glucoprivation is impaired in monosodium glutamate
      treated rats.
AB  - In the present study, newborn male Wistar rats were injected, subcutaneously,
      five times, every other day, with monosodium glutamate (MSG, 4 g/kg bw) or saline
      (as control, C), during the neonatal period. MSG animals developed destruction of
      the arcuate nuclei (ARC) with absence of NPY-immunoreactive cell bodies, which
      impaired both the food intake (baseline) and the 2-deoxy-D-glucose (2DG)
      glucoprivic feeding response. Increases in the immunoreactivity of corticotropin
      releasing hormone-cell bodies in the paraventricular nuclei might have developed
      to compensate for the atrophy of the pituitary in MSG-treated rats. After
      systemic 2DG injection, neither the C nor the MSG rats increased their food
      intake, but they showed similar hyperglycemic responses, whereas plasma free
      fatty acids (FFA) increased only in the C group. In other groups, 2DG,
      norepinephrine (NE), neostigmine (NEO) and saline were intracerebroventricularly
      (i.c.v.) administered. In this condition, impairment of the hyperglycemic and
      food intake responses, associated to a lower increase in plasma FFA levels, were
      observed. As opposed to this, the MSG treatment gives support to NE effects,
      enhancing food intake, as well as plasma glucose and FFA levels. After NEO,
      plasma glucose increased only in the MSG group, while plasma FFA levels were
      elevated in the C rats. Taken together, the results obtained after MSG treatment
      point to a separate neural control of the hyperglycemic response and of the lipid
      mobilization when stimulated by central 2DG, NE or NEO administration. It seems
      likely that the excitatory neural pathway that controls lipid metabolism and is
      present in C rats was destroyed by the MSG treatment.

PMID- 16406312
TI  - Pressor effects of the injection of noradrenaline into different
      cerebroventricular spaces in unanesthetized rats.
AB  - Injection of noradrenaline (NA) into the lateral cerebral ventricle (i.c.v.) was
      reported to cause blood pressure increase in unanesthetized rats, blocked by i.v.
      injection of vasopressin antagonists. We report similar responses to NA injection
      into the III or IV ventricles, suggesting multiple sites of action for i.c.v. NA.
      These responses were blocked by i.v. pretreatment with vasopressin antagonist,
      suggesting a common mediation by vasopressin release into circulation. Selected
      ventricular spaces were occluded with Nivea cream plugs to identify ventricular
      areas responding to i.c.v. NA. III ventricle or aqueduct occlusions markedly
      reduced pressor responses to i.c.v. NA. Microinjection of NA into the
      periaqueductal gray matter (PAG) caused pressor responses that were similar to
      those of i.c.v. NA, reinforcing the idea of a site of action in the aqueduct. IV
      ventricle occlusion only partially blocked the response to i.c.v. NA. The results
      suggest at least two sites of action for i.c.v. NA in unanesthetized rats. A
      primary site located in the PAG and another on the IV ventricle wall.

PMID- 16406313
TI  - Geranylgeranylacetone, a noninvasive heat shock protein inducer, induces protein
      kinase C and leads to neuroprotection against cerebral infarction in rats.
AB  - Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone
      (GGA), a heat shock protein (HSP) inducer, against ischemic insult. Protein
      kinase C (PKC) is thought to be an important factor that mediates the expression
      of heat shock protein 70 (HSP70) in vitro. However, the signaling pathways in the
      brain in vivo after oral GGA administration remain unclear. We measured and
      compared infarction volumes to investigate the effect of GGA on cerebral
      infarction induced by permanent middle cerebral artery (MCA) occlusion in rats.
      To clarify the relationship between PKC induction and HSP70 expression, we
      determined the amounts of HSP70 and PKC proteins after GGA administration by
      immunoblotting. We evaluated the effects of pretreatment with chelerythrine
      (CHE), a specific PKC inhibitor, on expressions of PKC and HSP70 proteins with
      immunoblotting. Neuroprotective effects of GGA (pretreatment with a single oral
      GGA dose (800 mg/kg) 48 h before ischemia) were prevented by CHE pretreatment,
      which indicates that PKC may mediate the GGA-dependent protection. Oral GGA
      induced HSP70 expression induced PKC delta, and GGA pretreatment enhanced
      ischemia-induced HSP70, both of which were prevented by CHE pretreatment. These
      results suggest that a single oral dose of GGA induces PKC delta and promotes
      HSP70 expression in the brain and that GGA plays an important role in
      neuroprotection against cerebral ischemia.

PMID- 16406314
TI  - Decreased phosphorylation and protein expression of ERK1/2 in the brain of
      hypoxic preconditioned mice.
AB  - Accumulated reports have suggested that activation of protein kinase C (PKC)
      isoforms may involve the activation of extracellular signal-regulated kinases 1/2
      (ERK1/2) in the neuronal response to hypoxic stimuli. We have previously
      demonstrated that the membrane translocation or activation of conventional PKC
      (cPKC) betaII, gamma and novel PKC (nPKC) epsilon are increased in the early
      phase of cerebral hypoxic preconditioning in mice. However, the role of ERK1/2 in
      the development of cerebral hypoxic preconditioning is unclear. In the current
      study, we used Western blot analysis to investigate the effects of repetitive
      hypoxic exposure (H0-H6, n=6 for each group) on the levels of phosphorylation and
      protein expression of ERK1/2 in the frontal cortex and the whole hippocampus of
      mice. We found that the levels of phosphorylated ERK1/2, not protein expression
      of ERK1/2, decreased significantly in both cortex and hippocampus of the early
      hypoxic preconditioned mice (H1-H4), when compared to that of the normoxic group
      (p<0.05). In addition, a significant decrease (p<0.05) in the ERK1/2 protein
      expression, not the phosphorylated form of ERK1/2, was found both in the frontal
      cortex and hippocampus of mice followed hypoxia with previous hypoxia (H5 and
      H6). These results suggest that the decreased phosphorylation and downregulation
      of protein expression of ERK1/2 might be involved in the development of hypoxic
      preconditioning.

PMID- 16406315
TI  - Neuronal inclusions in sporadic motor neuron disease are negative for alpha
      synuclein.
AB  - Alpha-synuclein has been implicated in neurodegenerative diseases characterized
      by Lewy bodies. However, we have only scanty information on the immunoreactivity
      of alpha-synuclein in other inclusion bodies such as the Lewy body-like
      inclusions and the skein-like inclusions observed in motor neuron disease (MND).
      In this report, we immunocytochemically investigated inclusion bodies observed in
      the anterior horn neurons of the spinal cord in 29 patients with sporadic MND.
      Sixteen age-matched patients without any neurological disease served as controls.
      In MND patients, we recognized Lewy body-like hyaline inclusions, skein-like
      inclusions, Bunina bodies, basophilic inclusions, and intracytoplasmic hyaline
      (colloid) inclusions, but none of them were immunostained for alpha-synuclein.
      Our findings in this study do not support the hypothesis that MND could be
      classified as one of the diseases grouped as alpha-synucleinopathies.

PMID- 16406316
TI  - Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild
      cognitive impairment?
AB  - There is a need for effective biomarkers showing whether or not a patient with
      mild cognitive impairment (MCI) will progress to Alzheimer's disease (AD) with
      dementia. At the present three cerebrospinal fluid (CSF) biomarkers are in
      general use: total tau, phospho-tau and beta-Amyloid. These markers are regarded
      to have high capacity to differentiate early AD from normal ageing. We have
      analysed CSF levels of a new marker for neuronal degeneration, 24S
      hydroxycholesterol (24OHC) in patients with MCI. For reasons of comparison, we
      also analysed these levels in patients with AD. There was a significant
      correlation between CSF levels of 24OHC and total tau (as well as phospho-tau) in
      both groups of patients. Fifty percent of the patients contemplated for MCI were
      found to have elevated levels of 24OHC (using a 95th upper percentile set cut
      off). All the MCI patients with normal levels of 24OHC had normal levels of the
      other markers. In patients with AD, the percentages of those with increased
      levels of 24OHC, tau and phospho tau were similar (55-67%). In this pilot study,
      we discuss the possibility that 24OHC may be a sensitive test for MCI.

PMID- 16406317
TI  - The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia
      in an Italian population sample.
AB  - Programmed cell death and alterations in intracellular G-protein signaling may be
      involved in the pathophysiology of schizophrenia. The Galphas subunit of
      heterotrimeric G-proteins, encoded by the gene GNAS1, may play a role in both of
      these processes. Additionally, transgenic mice expressing a constitutively active
      form of Galphas provide a reliable model of certain endophenotypes of
      schizophrenia. To investigate whether the functional single nucleotide
      polymorphism T393C in GNAS1 gene could affect risk of schizophrenia, we examined
      its distribution in Italian subjects with (n=383) and without (n=400)
      schizophrenia. We also evaluated whether a specific association could exist
      between the deficit (n=108) and nondeficit (n=275) forms of the disorder. The
      alleles and genotypes frequency in the entire cohort of schizophrenic patients
      did not differ from that of controls. However, the frequency of the homozygous
      393TT genotype was significantly higher in deficit schizophrenic patients (37.1%)
      compared to both nondeficit schizophrenic (22.5%, p=0.011) and controls (22.8%,
      p=0.015). This association with deficit schizophrenia persisted even after
      allowance for potential confounders [adjusted odds ratio (OR) for deficit
      schizophrenia: 2.06 (95% confidence interval (CI): 1.21-3.47), p=0.007].
      Altogether, our data suggest that the GNAS1 T393C status could influence
      susceptibility for deficit schizophrenia in Italian subjects.

PMID- 16406318
TI  - Angiotensin II sensitivity of anterior hypothalamic area neurons is enhanced in
      both spontaneously hypertensive rats and Dahl salt-sensitive rats.
AB  - We have previously demonstrated that some neurons in the anterior hypothalamic
      area (AHA) are tonically activated by endogenous angiotensins. Furthermore, we
      have demonstrated that intracerebroventricular injection of hypertonic saline
      increases the firing rate of AHA angiotensin II-sensitive neurons via
      angiotensins and that the central sodium-induced activation of AHA neurons is
      enhanced in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (Dahl
      S) rats. In this study, we examined whether sensitivities of AHA angiotensin II
      sensitive neurons to angiotensin II are enhanced in SHR and Dahl S rats as
      compared with their respective controls. Male 15- to 16-week-old SHR and age
      matched Wistar Kyoto rats (WKY), and male 15- to 16-week-old Dahl S rats and Dahl
      R rats were anesthetized and artificially ventilated. Extracellular potentials
      were recorded from single neurons in the AHA. In SHR, pressure application of
      angiotensin II (3 x 10(-9) to 3 x 10(-8) M) onto AHA angiotensin II-sensitive
      neurons increased their firing rate in a concentration-dependent manner. In WKY,
      only the highest concentration of angiotensin II increased the firing rate, while
      the lower concentrations of angiotensin II did not affect it. In Dahl S rats,
      pressure application of angiotensin II (10(-8) and 3 x 10(-8) M) onto AHA neurons
      increased their firing rate, while angiotensin II (3 x 10(-9) M) did not affect
      it. In Dahl R rats, the highest concentration of angiotensin II increased the
      firing rate, while the lower concentrations of angiotensin II did not affect it.
      These findings indicate that the sensitivity of AHA neurons to angiotenisn II is
      enhanced in SHR and Dahl S rats as compared with their respective controls.

PMID- 16406319
TI  - Activation of protein kinase C enhances 1-methyl-4-phenylpyridinium ion (MPP+)
      induced hydroxylradical generation in rat striatum.
AB  - The present study examined the effect of chelerlythrine, a protein kinase C (PKC)
      inhibitor, on 1-methyl-4-phenylpyridine (MPP+)-induced hydroxyl radicals (*OH) in
      rat striatum. Rats were anesthetized, and sodium salicylate (0.5 mM or 0.5
      nmol/microl/min) was infused through a microdialysis probe to detect the *OH
      generation as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic
      acid (2,3-DHBA) in the striatum. Dopamine (DA)-selective neurotoxin, MPP+,
      infusion into the striatum of rats induces *OH formation, trapped as 2,3-DHBA.
      The application of chelerythrine, a potent and selective protein kinase C (PKC)
      inhibitor, suppressed MPP+ -induced *OH formation. The results in the present
      study suggests the protective effect of chelerythrine on *OH generation induced
      by MPP+.

PMID- 16406320
TI  - CXCL16 is elevated in the cerebrospinal fluid versus serum and in inflammatory
      conditions with suspected and proved central nervous system involvement.
AB  - In neuro-inflammatory diseases, activated T cells are thought to drive the
      inflammatory process. In this study, we investigated the potential role of three
      T cell attracting chemokines (CK) in neuro-inflammation. For this purpose, we
      measured levels of CXCL16, CCL17 and CCL18 in matched serum and cerebrospinal
      fluid (CSF) samples of patients with different neurological diseases.
      Interestingly, CXCL16 levels were significantly elevated in the CSF and were
      higher in inflammatory disease than in controls, whereas CCL17 and CCL18 were
      absent in the CSF. CCL18 was only elevated in serum of SLE patients. These data
      suggest that attraction of activated memory type T cells by CXCL16 might play an
      important role in the orchestration of immune responses in the central nervous
      system.

PMID- 16406321
TI  - Candidate gene analysis of the succinic semialdehyde dehydrogenase gene (ALDH5A1)
      in patients with idiopathic generalized epilepsy and photosensitivity.
AB  - Succinic semialdehyde dehydrogenase (SSADH) is involved in the degradation of the
      inhibitory neurotransmitter GABA and about 50% of patients with SSADH deficiency
      suffer from seizures. The gene encoding SSADH (gene symbol: ALDH5A1) maps in
      proximity to susceptibility loci for juvenile myoclonic epilepsy (JME) and
      photosensitivity on chromosome 6p22. The present study tested whether variation
      of the ALDH5A1 gene confers susceptibility to common syndromes of idiopathic
      generalized epilepsy (IGE) and an abnormal photoparoxysmal response (PPR).
      Mutation screening of the ALDH5A1 coding sequence of 35IGE/PPR patients and four
      healthy control subjects identified 17 sequence variants, of which three resulted
      in an exchange of amino acids (H180Y, P182L, A237S). Association analysis was
      carried out for six single nucleotide polymorphisms (SNPs) and one trinucleotide
      repeat polymorphism (TNR, intron 1), covering the genomic ALDH5A1 sequence. The
      study sample comprised 566 unrelated German IGE patients, including 218 JME and
      95 photosensitive IGE patients, 78 PPR probands without IGE, and 662 German
      population controls. None of the investigated ALDH5H1 polymorphisms showed
      evidence for an allelic or genotypic association with either IGE, JME, or PPR,
      when corrected for multiple tests. A tentative haplotypic association of the two
      marker haplotype (rs1883415-TNR) covering the 5'-regulatory region in IGE
      patients (chi2=11.65, d.f.=3, P=0.009) warrants further replication studies. The
      present results do not provide evidence that any ALDH5A1 missense variant itself
      contributes a common and substantial susceptibility effect (RR>2) to IGE
      syndromes or an increased liability to visually-induced cortical synchronization.

PMID- 16406322
TI  - WIN 55212-2 impairs contextual fear conditioning through the activation of CB1
      cannabinoid receptors.
AB  - The memory deficits induced by cannabinoid agonists have been found in several
      behavioral paradigms. Nevertheless, there is evidence that not all types of
      memory are impaired after cannabinoid administration. The aim of this study was
      to investigate whether the cannabinoid agonist WIN 55212-2 (WIN) is able to
      influence the acquisition of fear conditioning using tone and contextual
      versions. For tone-fear conditioning, male Wistar rats were placed in the
      conditioning chamber and after 3 min, a sound (CS) was presented for 10s that
      terminated with a 1-s electric footshock (1.5 mA). For contextual-fear
      conditioning, a similar procedure was used but no sound was presented. Twenty
      four hours after, the animals were re-exposed to the respective CS (tone or
      conditioning chamber) and the freezing behavior was registered. A subsequent
      experiment investigated a possible state-dependent effect of WIN by administering
      WIN or control solution 30 min before conditioning and before testing. WIN (2.5
      and 5.0 mg/kg) administered i.p. 30 min before impaired contextual fear
      conditioning but did not modify the freezing behavior elicited by tone
      presentation. These animals did not show any state-dependent effects of WIN.
      Further, the impaired contextual conditioning was prevented by preadministration
      of SR141716A (1.0 mg/kg, i.p.) or SR147778 (1.0 mg/kg, i.p.), selective
      cannabinoid CB1 receptor antagonists. The present findings highlight that
      cannabinoid agonists effects are selective for the hippocampus-dependent aversive
      memories in rats. This effect appears to be related to the activation of CB1
      cannabinoid receptors and confirms that cannabinoids might provide a novel
      approach for the treatment of unpleasant memories.

PMID- 16406323
TI  - Epidermal growth factor (EGF) expression in lateral line system and in taste buds
      of adult zebrafish (Brachidanio rerio).
AB  - The mechano and chemosensory organs of adult teleosts undergoes a continuous cell
      renewal and turnover which is regulated in part by growth factors. Here, we
      investigated the occurrence and the cell localization of epidermal growth factor
      (EGF) in the lateral line system and taste bud of adult zebrafish, using Western
      blot and immunohistochemistry associated to a polyclonal antibody against
      mammalian EGF. Furthermore, the distribution of S100 protein was studied in
      parallel to label hair sensory cells in the lateral line system. Western blot
      revealed one unique protein band with an estimated molecular weight of about 13
      kDa, equivalent to the EGF of mammals. Specific immunoreactivity for EGF was
      observed in the epithelial basal and/or supporting cells of the neuromasts of the
      lateral line system and taste buds. Conversely, the sensory cells in both sensory
      structures were devoid of immunostaining. Present results demonstrate the
      occurrence of EGF in mechano and sensory system of adult zebrafish, suggesting a
      role for this molecule in the cell renewal and turnover of these structures.

PMID- 16406324
TI  - Generation of cerebellar neuron precursors from embryonic stem cells.
AB  - Here, we report in vitro generation of Math1+ cerebellar granule cell precursors
      and Purkinje cells from ES cells by using soluble patterning signals. When neural
      progenitors induced from ES cells in a serum-free suspension culture are
      subsequently treated with BMP4 and Wnt3a, a significant proportion of these
      neural cells become Math1+. The induced Math1+ cells are mitotically active and
      express markers characteristic of granule cell precursors (Pax6, Zic1, and
      Zipro1). After purification by FACS and coculture with postnatal cerebellar
      neurons, ES cell-derived Math1+ cells exhibit typical features of neurons of the
      external granule cell layer, including extensive motility and a T-shaped
      morphology. Interestingly, differentiation of L7+/Calbindin-D28K+ neurons
      (characteristic of Purkinje cells) is induced under similar culture conditions
      but exhibits a higher degree of enhancement by Fgf8 rather than by Wnt3a. This is
      the first report of in vitro recapitulation of early differentiation of
      cerebellar neurons by using the ES cell system.

PMID- 16406326
TI  - Joint action: bodies and minds moving together.
AB  - The ability to coordinate our actions with those of others is crucial for our
      success as individuals and as a species. Progress in understanding the cognitive
      and neural processes involved in joint action has been slow and sparse, because
      cognitive neuroscientists have predominantly studied individual minds and brains
      in isolation. However, in recent years, major advances have been made by
      investigating perception and action in social context. In this article we outline
      how studies on joint attention, action observation, task sharing, action
      coordination and agency contribute to the understanding of the cognitive and
      neural processes supporting joint action. Several mechanisms are proposed that
      allow individuals to share representations, to predict actions, and to integrate
      predicted effects of own and others' actions.

PMID- 16406325
TI  - Dystroglycan is required for proper retinal layering.
AB  - Dystroglycan (DG) is a transmembrane receptor linking the extracellular matrix to
      the internal cytoskeleton. Its structural function has been mainly characterized
      in muscle fibers, but DG plays signaling and developmental roles also in
      different tissues and cell types. We have investigated the effects of
      dystroglycan depletion during eye development of Xenopus laevis. We have injected
      a specific morpholino (Mo) antisense oligonucleotide in the animal pole of one
      dorsal blastomere of embryos at four cells stage. Mo-mediated loss of DG function
      caused disruption of the basal lamina layers, increased apoptosis and reduction
      of the expression domains of specific retinal markers, at early stages. Later in
      development, morphants displayed unilateral ocular malformations, such as
      microphtalmia and retinal delayering with photoreceptors and ganglion cells
      scattered throughout the retina or aggregated in rosette-like structures. These
      results recall the phenotypes observed in specific human diseases and suggest
      that DG presence is crucial at early stages for the organization of retinal
      architecture.

PMID- 16406328
TI  - Diversity of the infracommunities of strongylid nematodes in the ventral colon of
      Equus caballus from Rio de Janeiro state, Brazil.
AB  - Nematodes from the ventral colon of 31 adult horses, 24 males and 9 females, in
      the metropolitan region of the state of Rio de Janeiro were analysed. There were
      53,444 (86.4%) adults of the total recovered strongylid nematodes. They belonged
      to 21 species of Cyathostominae and seven of Strongylinae. Larval forms made up
      13.6% (8407) of the total recovered, and 49% of the strongylid nematodes were
      observed in ventral colon. The most prevalent and abundant species were
      Cyathostomum tetracanthum, Cylicocyclus nassatus, Cylicostephanus minutus,
      Cylicostephanus longibursatus, Cylicostephanus leptostomus, Cylicostephanus
      calicatus and Cylicostephanus goldi, corresponding to 93.2% of the total adult
      population; these species were classified as central species, except C. goldi;
      and other species were classified as secondary (n = 8) and satellite (n = 14).
      The low Green's aggregation index, presented to central species, indicated high
      dispersion because they were found in a greater number of infracommunities and
      were proven by the greater prevalence. Only 12.1% of the horses were uninfected
      or infected by a single species; the other infections were multiple, ranging from
      3 to 23 species.

PMID- 16406327
TI  - Inhibition of tumor metastasis in vivo by combination of paclitaxel and
      hyaluronic acid.
AB  - There is little information about the inhibitory effects of hyaluronic acid with
      paclitaxel on tumor metastasis and ascites formation. The aim of present study is
      to determine whether the combined administration of hyaluronic acid (HA) with
      paclitaxel can produce additional or synergistic therapeutic effects in the
      control of Lewis lung carcinoma (LLC) migration and ascites formation of U14
      cervical tumor. The anti-metastasis effect of hyaluronic acid alone, paclitaxel
      alone and paclitaxel-hyaluronic acid combination were examined in a mouse model
      bearing LLC cells. i.v. Paclitaxel-hyaluronic acid, in the ratio of 1:3 (w/w),
      significantly reduced the migration of LLC cells in a synergistic fashion. In the
      experiment with mice bearing U14 tumor cells, i.p. paclitaxel-hyaluronic acid
      markedly improved the life span of mice and significantly decreased ascites
      formation when compared to paclitaxel alone or hyalunonan alone. We also analyzed
      the serum proteome of mice with lung neoplasm before and after treatment with
      paclitaxel-hyaluronic acid. Proteomic analysis on LLC mice was studied using two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry.
      The results showed that i.v. administration of hyaluronic acid in combination
      with paclitaxel had significantly up-regulated the expression of vitamin D(3)
      binding proteins (DBP), which is a macrophage-stimulating activator. In
      conclusion, the in vivo anti-metastasis effect was associated with the
      synergistic therapeutic effects of hyaluronic acid-paclitaxel combination and a
      significant promotion of immune proteins expression. These results demonstrated
      that the combination of paclitaxel and hyaluronic acid may be an effective way to
      inhibit tumor migration.

PMID- 16406329
TI  - World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.)
      guidelines for evaluating the efficacy of acaricides against (mange and itch)
      mites on ruminants.
AB  - These guidelines have been prepared to assist in the planning, conduct and
      interpretation of studies for the assessment of the efficacy of acaricides
      against mange and itch mites on ruminants. Information is provided on the
      selection of animals, dose determination, dose confirmation and field studies,
      record keeping and result interpretation. These guidelines also are intended to
      assist the investigators on how to conduct specific experiments, to provide
      specific information for registration authorities involved in the decision-making
      process, to assist in the approval and registration of new ectoparasiticides, and
      to facilitate the worldwide adoption of standard procedures.

PMID- 16406330
TI  - Application of repeated bulk milk testing for identification of infection
      dynamics of Neospora caninum in Thai dairy herds.
AB  - In this prospective study, repeated bulk milk tests were evaluated to establish
      the Neospora caninum antibody status and to describe infection dynamics and
      changes in prevalence of N. caninum in Thai dairy herds. Bulk milk from 418 herds
      in northeast Thailand were collected at three consecutive samplings, in December
      2002 (sampling 1), April (sampling 2) and December 2003 (sampling 3). All samples
      were analysed for presence of N. caninum antibodies by iscom ELISA, and the
      optical density values were dichotomized at three different cut-offs. Herd status
      at either sampling 1 or sampling 2 was used to predict herd status at sampling 3.
      Changes in both sensitivity and specificity at the first samplings at all cut
      offs were consistent with commonly seen patterns when evaluating performance of
      diagnostic tests. In addition, the predictive positive values (PPV) of herd
      status at each of the two samplings were more affected by time of sampling than
      choice of cut-off, whereas the predictive negative values (PNV) increased with
      increasing cut-off. Herd status at the first samplings was also interpreted in
      combination, i.e. herds that were negative at both samplings were considered
      negative and positive otherwise in Combination A, while herds positive at both
      samplings were considered positive in Combination B. When using these
      combinations, Combination A gave higher PNV but lower PPV than Combination B at
      all cut-offs. Using the optical density value 0.20 as cut-off to establish the
      herd N. caninum antibody status, 270 herds (65%) kept their status throughout the
      study period, but 148 herds converted their status at least once. Interestingly,
      136 (86%) of the 158 herds that were considered negative at sampling 1 and
      sampling 2 remained negative at sampling 3. In addition of the 159 herds
      considered positive at the first two samplings, 134 (84%) were still positive at
      sampling 3. We concluded that repeated bulk milk testing at regular intervals
      provided better information about herd N. caninum status than a single test.
      Further, our results showed that the infection is prevalent in northeast
      Thailand, but that a herd can keep a negative infection status despite the
      frequent presence of dogs.

PMID- 16406331
TI  - Towards the eradication of Haemonchus contortus from sheep flocks in Sweden.
AB  - Previous studies have shown that between-year transmission of Haemonchus
      contortus in Swedish sheep flocks is almost entirely as over-wintered populations
      within housed animals, and not on pasture. This suggests that eradication of this
      parasite is a realistic possibility. Thus, two sheep farms with a history of H.
      contortus infection on the Swedish island of Oland were selected for study.
      During the winter housing period of 2003/2004 all ruminants (sheep and cattle) on
      both farms were treated with ivermectin. Monitoring by faecal egg counts and
      infective larval differentials of ewes and lambs for the subsequent two grazing
      seasons, together with total abomasal worm counts of 10 lambs from each farm at
      the end of the first grazing year, showed that this objective was achieved.

PMID- 16406332
TI  - New medicines from nature's armamentarium.
AB  - Nature frequently unleashes a barrage of new and frightening diseases against
      humans--such as HIV, severe acquired respiratory syndrome, Ebola virus and avian
      flu recently--in addition to the seemingly ever-present scourges such as malaria
      and tuberculosis. Fortunately, nature also provides the wherewithal to help
      conquer the diseases that it sets loose. All that is needed is the human
      ingenuity to discover, develop and apply the solutions in an optimal fashion.
      Participants at the 9th Max Tishler Memorial Symposium (Tokyo, July 2005) were
      told about several new advances in the search for new anti-infective drugs
      derived from natural sources and were able to learn how one of the most effective
      drugs ever, ivermectin, made its way through what was, at the time, uncharted
      territory and how precedents were set at nearly every stage to form a model for
      all subsequent public-private partnerships.

PMID- 16406333
TI  - Wolbachia genomes: revealing the biology of parasitism and mutualism.
AB  - Wolbachia bacteria are endosymbiotic partners of many animal species, in which
      they behave as either parasites (in arthropod hosts) or mutualists (in nematode
      hosts). What biochemistry and biology underpin these diverse lifestyles? The
      recent complete sequencing of genomes from Wolbachia that infect the arthropod
      Drosophila melanogaster and the nematode Brugia malayi, together with the partial
      genome sequencing of three Wolbachia strains found in drosophilids, enables this
      question to begin to be addressed. Parasitic arthropod Wolbachia are
      characterized by the presence of phages that carry ankyrin-repeat proteins; these
      proteins might be exported to the host cell to manipulate reproduction. In
      nematode Wolbachia, which lack these phages, several biochemical pathways can
      deliver essential metabolites to the nematode hosts. Nematode Wolbachia might
      also have a role in modulating the mammalian host immune system but the sequenced
      Wolbachia genomes lack the genes to synthesize lipopolysaccharide, raising
      questions about the nature of the inducing molecule. The Wolbachia surface
      protein might carry out this function.

PMID- 16406335
TI  - Microwave thermal inertisation of asbestos containing waste and its recycling in
      traditional ceramics.
AB  - Asbestos was widely used as a building material prior to the 1970's. It is well
      known that asbestos is a health hazard and its progressive elimination is a
      priority for pollution prevention. Asbestos can be transformed to non-hazardous
      silicate phases by microwave thermal treatment. The aim of this investigation is
      to describe the microwave inertization process of asbestos containing waste (ACW)
      and its recycling in porcelain stoneware tiles, porous single-fired wall tiles
      and ceramic bricks following industrial manufacture procedure. Inertised asbestos
      powder was added in the percentages of 1, 3, and 5 wt.% to commercially available
      compositions and then fired following industrial thermal cycles. Water absorption
      and linear shrinkage of the obtained industrial products do not present
      significant variations with additions up to 5 wt.% of microwave inertised ACW.

PMID- 16406336
TI  - Degradation and detoxification of formaline wastewater by advanced oxidation
      processes.
AB  - In this study, advanced oxidation processes (AOPs) utilizing the combinations of
      UV/H(2)O(2), Fenton, photo-Fenton and the combination of Fenton/photo-Fenton
      reactions were investigated in lab-scale experiments for the degradation of
      formaline wastewater. The studied toxic chemicals were formaldehyde and methanol
      in mixture solution, so-called formalin, which is the embalming agent in
      mortuaries. The experimental results showed that the photo-Fenton process was the
      most effective treatment process among the studied AOPs. Pseudo-first-order
      degradation rate constants of formaldehyde and methanol were obtained from batch
      experimental data. In the combination of Fenton/photo-Fenton reactions, the
      results show that applying UV light at an early stage of the reaction might not
      be necessary for a speedy oxidation reaction of the Fenton process. With Fenton
      and photo-Fenton processes, mineralization of formaline wastewater can be
      achieved, as no residual TOC is detected in the effluent after the reaction
      period. It is suggested that Fenton and photo-Fenton processes are viable
      techniques for the formaline wastewater treatment as they were able to provide
      high degradation of formaldehyde and methanol with relatively low toxicity of the
      by-products in the effluent.

PMID- 16406337
TI  - Batch study of liquid-phase adsorption of methylene blue using cedar sawdust and
      crushed brick.
AB  - This paper presents a study on the batch adsorption of basic dye, methylene blue,
      from aqueous solution (40 mg L(-1)) onto cedar sawdust and crushed brick in order
      to explore their potential use as low-cost adsorbents for wastewater dye removal.
      Adsorption isotherms were determined at 20 degrees C and the experimental data
      obtained were modelled with the Langmuir, Freundlich, Elovich and Temkin isotherm
      equations. Adsorption kinetic data determined at a temperature of 20 degrees C
      were modelled using the pseudo-first and pseudo-second-order kinetic equations,
      liquid-film mass transfer and intra-particle diffusion models. By considering the
      experimental results and adsorption models applied in this study, it can be
      concluded that equilibrium data were represented well by a Langmuir isotherm
      equation with maximum adsorption capacities of 142.36 and 96.61 mg g(-1) for
      cedar sawdust and crushed brick, respectively. The second-order model best
      describes adsorption kinetic data. Analysis of adsorption kinetic results
      indicated that both film- and particle-diffusion are effective adsorption
      mechanisms. The Influence of temperature and pH of the solution on adsorption
      process were also studied. The extent of the dye removal decreased with
      increasing the solution temperature and optimum pH value for dye adsorption was
      observed at pH 7 for both adsorbents. The results indicate that cedar sawdust and
      crushed brick can be attractive options for dye removal from dilute industrial
      effluents.

PMID- 16406338
TI  - Functional expression of lepidopteran-selective neurotoxin in baculovirus:
      potential for effective pest management.
AB  - Recombinant baculovirus expressing insect-selective neurotoxins derived from
      venomous animals are considered as an attractive alternative to chemical
      insecticides for efficient insect control agents. Recently we identified and
      characterized a novel lepidopteran-selective toxin, Buthus tamulus insect
      selective toxin (ButaIT), having 37 amino acids and eight half cysteine residues
      from the venom of the South Indian red scorpion, Mesobuthus tamulus. The
      synthetic toxin gene containing the ButaIT sequence in frame to the bombyxin
      signal sequence was engineered into a polyhedrin positive Autographa californica
      nuclear polyhedrosis virus (AcMNPV) genome under the control of the p10 promoter.
      Toxin expression in the haemolymph of infected larvae of Heliothis virescens and
      also in an insect cell culture system was confirmed by western blot analysis
      using antibody raised against the GST-ButaIT fusion protein. The recombinant NPV
      (ButaIT-NPV) showed enhanced insecticidal activity on the larvae of Heliothis
      virescens as evidenced by a significant reduction in median survival time (ST50)
      and also a greater reduction in feeding damage as compared to the wild-type
      AcMNPV.

PMID- 16406339
TI  - p63 and epithelial biology.
AB  - The transcription factor p63 is a homologue of the tumor suppressor p53. Unlike
      p53, which is dispensable for normal development, p63 is critical for the
      development of stratified epithelial tissues such as epidermis, breast, and
      prostate. p63 encodes multiple protein isoforms with both transactivating and
      transcriptional repressor activities that can regulate a wide spectrum of target
      genes. p63 is also implicated in tumor formation and progression in stratified
      epithelia, with evidence for both tumor suppressive and oncogenic properties.
      This review will examine current data and hypotheses regarding the role of p63 in
      the development, maintenance, and tumorigenesis of stratified epithelium.

PMID- 16406341
TI  - The characteristics of the nogo-N140 component in somatosensory go/nogo tasks.
AB  - Nogo-related brain potentials may not be dependent on sensory modalities but
      reflect common neural activities specific to the inhibitory process. Recent
      studies reported that nogo potentials were elicited by not only visual and
      auditory but also somatosensory stimulation. However, the characteristics of this
      nogo potential evoked by somatosensory stimulation have been unclear because of
      the small number of reports. In the present study, therefore, to determine the
      characteristics of this potential, the effects of stimulus site and response hand
      were investigated. Electrical stimulation was delivered to the second and fifth
      digit of one hand, and the subjects had to respond to a go stimulus by pushing a
      button with the thumb contralateral to the stimulated side as quickly as
      possible. The amplitudes of the nogo-N140 component (N140 evoked by the nogo
      stimuli), which is very similar to the nogo-N2 components following visual and
      auditory stimulation, were unrelated to the stimulated digits, the second and
      fifth digit of the left and right hand. However, differences between go and nogo
      ERPs were significantly larger in the hemisphere contralateral to the response
      hand than the ipsilateral hemisphere. This result was inconsistent with visual
      and auditory go/nogo studies showing a right-hemisphere dominance or bilateral
      activities in nogo trials. Therefore, nogo-N140 should be considered to reflect
      the inhibitory process especially in the hemisphere contralateral to the response
      hand and the sensory modality dependency of nogo potentials.

PMID- 16406340
TI  - The role of nitric oxide in abnormal T cell signal transduction in systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
      by production of antinuclear autoantibodies and diverse array of clinical
      manifestations. T cells from patients with SLE have been shown to be activated in
      vivo and provide help to autoreactive B cells. Lupus T cells exhibit enhanced
      spontaneous and diminished activation-induced apoptosis and predisposition to
      necrosis. Persistent mitochondrial hyperpolarization and ATP depletion -
      associated with significantly increased mitochondrial mass - characterize T
      lymphocyte dysfunction in SLE. In addition to cell death abnormalities,
      mitochondrial dysfunction is associated with altered signal transduction through
      the T cell receptor and Ca2+ fluxing. Exposure of normal T cell to nitric oxide
      induces mitochondrial hyperpolarization and biogenesis and regenerates the Ca2+
      signaling profile of lupus T cells. This article reviews a novel understanding of
      the role of nitric oxide in signal transduction and cell death abnormalities in
      SLE.

PMID- 16406342
TI  - NSAID zaltoprofen possesses novel anti-nociceptive mechanism through blockage of
      B2-type bradykinin receptor in nerve endings.
AB  - Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs
      (NSAIDs), was shown to have more powerful inhibitory effects to bradykinin (BK)
      nociception than other NSAIDs. However, the molecular mechanisms underlying this
      potent analgesia are not yet fully understood. Here we attempted to clarify the
      molecular mechanism underlying zaltoprofen-induced analgesia on BK-induced
      nociception by a novel algogenic-induced paw flexion (APF) test in mice. The
      intraplantar (i.pl.) injection of zaltoprofen at 1nmol showed strong analgesic
      action on BK (i.pl.)-induced nociceptive flexor responses, whereas loxoprofen or
      its active metabolite loxoprofen-SRS did not. Zaltoprofen also inhibited the
      nociception induced by [Tyr8]-BK, a specific agonist of B2-type BK receptor, but
      did not affect the nociception by [Lys-des-Arg9]-BK, a specific agonist of B1
      type BK receptor. However, zaltoprofen did not affect the substance P-induced
      nociception, which is mediated by common post-receptor signaling through
      nociceptive fibers with BK-ones. All these results suggest that NSAID zaltoprofen
      possesses novel anti-nociceptive mechanism, which inhibits B2-type BK receptor
      function in nerve endings.

PMID- 16406344
TI  - Physical exercise facilitates motor processes in simple reaction time
      performance: an electromyographic analysis.
AB  - The aim of the current study was to assess the effects of physical exercise on
      simple reaction time performance. Participants performed a simple reaction time
      task twice, one time during physical exercise and another time without exercise.
      Electromyographic signals were recorded from the thumb of the responding hand to
      fraction reaction time in pre-motor and motor time. The results showed that
      exercise shortened motor time but failed to affect pre-motor time. This pattern
      of findings is consistent with previous studies examining the effects of physical
      exercise on choice reaction time.

PMID- 16406343
TI  - Electroacupuncture improves restraint stress-induced delay of gastric emptying
      via central glutaminergic pathways in conscious rats.
AB  - Acupuncture has been used for treating functional gastrointestinal (GI)
      disorders. Animal studies demonstrated that acupuncture improves various stress
      induced physiological responses. We investigated the effects of
      electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced delay of
      gastric emptying. Solid food gastric emptying in 90 min was significantly delayed
      by restraint stress (27.3 +/- 2.1%, n = 8), compared to that of controls (64 +/-
      2.1%, n = 8). Restraint stress-induced delay of gastric emptying was
      significantly restored by the intracisternal (IC)-injection of GABA(A) receptor
      antagonist, bicuculline methiodide (46.5 +/- 3.1%; n = 6) and GABA(B) receptor
      antagonist, phaclofen (48 +/- 3.3%; n = 6). Delayed gastric emptying induced by
      restraint stress was significantly improved by EA at ST-36 (49.7 +/- 1.4%). The
      stimulatory effect of EA on stress-induced delay of gastric emptying was
      prevented by pretreatment with IC-injection of glutamate receptor antagonist,
      kynurenic acid (30.1 +/- 2.1%). In conclusion, restraint stress-induced delay of
      gastric emptying is mediated via central GABA(A) and GABA(B) receptors. EA at ST
      36 stimulates glutaminergic neurons in the brainstem resulting in improvement of
      stress-induced delay of gastric emptying.

PMID- 16406345
TI  - Phospholipase A2 is involved in muscarinic receptor-mediated sAPPalpha release
      independently of cyclooxygenase or lypoxygenase activity in SH-SY5Y cells.
AB  - The release of soluble amyloid precursor protein alpha (sAPPalpha), produced
      during alpha-secretase processing by cleavage within the beta amyloid peptide
      domain of APP, is highly regulated by several external and internal signals.
      Because evidence suggests the involvement of inflammatory processes in the
      pathology of Alzheimer's disease and APP formation, we examined the involvement
      of the phospholipase A2 (PLA2) pathway and of its downstream cyclooxygenase (COX)
      and lipoxygenase (LOX) pathways in the regulation of sAPPalpha, release induced
      by muscarinic receptor activation in SH-SY5Y cells. The amount of sAPP released
      into the culture medium was analyzed using a monoclonal 6E10 antibody detecting
      sAPPalpha. Treatment with the PLA2 inhibitor, manoalide, blocked the release of
      oxoM (muscarinic receptor agonist)-stimulated sAPPalpha, and the muscarinic
      receptor-mediated sAPPalpha release was increased by the non-selective PLA2
      activator mellitin. COX and LOX inhibitors inhibited exogenous AA-induced
      sAPPalpha release, but upregulated basal constitutive sAPPalpha release. However,
      treatment with COX or LOX inhibitors failed to significantly change oxoM
      stimulated sAPPalpha release, and furthermore, muscarinic receptor activation
      inhibited AA-stimulated COX activity. Our results suggest that sAPPalpha release
      induced by muscarinic receptor activation is regulated by AA generation via PLA2
      activation independently of COX and LOX activities, but that the COX and LOX
      pathways are possibly involved in the constitutive release of sAPPalpha.

PMID- 16406346
TI  - The impact of PCO2 and H+ on the release of acetylcholine from the cat carotid
      body.
AB  - The carotid body (CB) is a sensor of oxygen, carbon dioxide, hydrogen ion, and
      glucose in the arterial blood. Many studies of the CB's responses to low oxygen
      (hypoxia) have been reported. Recently attention has been increasingly focused on
      its responses to elevated CO2 (hypercapnia). An increase in ventilation or
      carotid body neural output (CBNO) can result from stimulating the CB with blood
      or perfusion fluids having an elevated CO2 or H+. The increase in ventilation
      seen with a hypoxic stimulus is accompanied with an increase in CBNO and an
      increased release of both acetylcholine (ACh) and ATP from the CB. The present in
      vitro study using both CBs harvested from six cats was undertaken to determine if
      hypercapnia also provoked an increased release of ACh from the incubated CBs. The
      anesthetizing, handling, and euthanizing of the animals were according to the
      guidelines of the Johns Hopkins Animal Care and Use Committee which are totally
      consonant with those of the NIH. CBs, once harvested and prepared for the
      experimental protocol, were subjected to the following steps each lasting 10 min:
      (1) control; (2) stress; (3) recovery. The stresses were respiratory acidosis
      (RAC; acidic hypercapnia), compensated respiratory acidosis (CRAC; isohydric
      hypercapnia), and metabolic acidosis (MtAC). The first and last forms of acidosis
      generated small but significant increases in the release of ACh from the CBs; the
      second generated a very small and insignificant increase in ACh release. Since it
      is generally accepted that ACh is a key excitatory neurotransmitter in the CB
      along with ATP, these data are consistent with other studies measuring the
      increase in ventilation in response to a small increase in CO2 and those studies
      recording CBNO in response to hypercapnia. In five of the six animals the
      responses to RAC and MtAC were compared to the responses to hypoxia. The latter
      were statistically indistinguishable from the former two.

PMID- 16406347
TI  - Reduced hippocampal volume in non-demented carriers of the apolipoprotein E
      epsilon4: relation to chronological age and recognition memory.
AB  - Apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor
      for Alzheimer's disease (AD). Some previous studies have reported structural
      brain changes as well as cognitive deficits in non-demented APOE epsilon4
      carriers, but the pattern of results is inconsistent and studies with larger
      sample sizes have been called for. Here we compared hippocampal volume and
      recognition-memory performance between AD-symptom-free carriers (N=30) and non
      carriers (N=30) of the APOE epsilon4 (age range: 49-79 years). We observed
      reduced right hippocampal volume in APOE epsilon4 carriers, and found that the
      difference was most pronounced before the age of 65. Further, the APOE epsilon4
      carriers made significantly more false alarms in the recognition-memory test, and
      the number of false alarms correlated significantly with right hippocampus
      volume. These results indicate that relatively young individuals at genetic risk
      for AD have smaller hippocampal volume and lower performance on hippocampal
      dependent cognitive tasks. A question for the future is whether smaller
      hippocampal volume represents early-onset hippocampal volume reduction or an
      inherent trait.

PMID- 16406348
TI  - Immune system evasion by peripheral nerve sheath tumor.
AB  - Mechanisms by which tumor cells evade detection by the host's immune system are
      thought to play a role in progression to malignancy, but this has not been
      investigated in the context of neurofibromatosis type 1 (NF1). NF1 is an
      autosomal dominant disorder, in which aggressive peripheral nerve tumors, known
      as malignant peripheral nerve sheath tumors (MPNSTs), develop in 5-10% of
      patients. Large scale gene expression profiling of a MPNST-derived cell line,
      T265, and normal human Schwann cells (hSCs) identified a large group of immune
      function genes down-regulated in T265 cells. Here we report that the aberrant
      expression of immune system related genes extends beyond MHC class I and II genes
      in T265 cells to include a transcription factor (MHC2TA) and other critical
      components of the antigen processing and presentation apparatus. TAP1, the
      transporter-activator protein that loads peptide antigens onto MHC class I
      molecules, is down-regulated, and CD74, a chaperone protein whose function is in
      processing and transport of MHC class II molecules, is down-regulated and
      alternatively spliced to produce an RNA transcript not evident in normal human
      Schwann cells. These findings reveal multiple molecular pathways and at least two
      cellular mechanisms acting to reduce the normal immune system molecules involved
      in antigen processing and presentation in cells derived from a peripheral nerve
      sheath tumor. Acquiring a "silent" immune signature may be a critical step in the
      progress towards malignancy in MPNSTs.

PMID- 16406349
TI  - Observational study on the stability of the psychological status during normal
      pregnancy and increased blood levels of neuroactive steroids with GABA-A receptor
      agonist activity.
AB  - We investigated whether pregnancy could modify psychological symptoms and whether
      neuroactive steroids which exert an anti-anxiety effect by acting on the gamma
      aminobutyric acid (GABA)-A receptors, are modified during pregnancy in young
      healthy women. Healthy volunteer women in the Department of Obstetrics and
      Gynecology at Cagliari University participated in the study. They were divided
      into women with low (group 1, seven subjects) and high (group 2, seven subjects)
      psychological score by SCL-90 psychometric scale. Age, body mass index and
      physiological status of pregnancy did not differ between the groups. The subjects
      were studied before pregnancy during the follicular phase (FP), and the luteal
      phase (LP) of the menstrual cycle (MC) and four times during pregnancy (at 14th,
      22nd, 30th, and 38th week). SCL-90 psychometric scale, circulating levels of
      progesterone (P4), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, AP),
      3alpha,21-dihydroxy-5alpha-pregnan-20-one (allotetrahydrodeoxy-corticosterone,
      THDOC), cortisol and DHEAS were assayed at each visit. The SCL-90 global score
      and the intensity of psychological symptoms differ between the groups, but within
      each group they did not change both during MC and during pregnancy. The DHEAS and
      cortisol levels did not differ between the groups. DHEAS did not change during
      the study, whereas cortisol levels increased during pregnancy in both groups.
      Progesterone, AP, and THDOC levels were higher during LP than during FP and
      further increased during pregnancy, without any difference between the groups. In
      conclusion, pregnancy does not seem to interfere with the psychological status of
      healthy women independently of the psychological basal score. Some neuroactive
      steroids with anxiolytic activity seem to increase during pregnancy depending on
      placental function. Their increase could represent some kind of protection
      against maternal anxiety and stress due to concerns about the pregnancy outcome.

PMID- 16406350
TI  - Fusion of neural stem cells in culture.
AB  - An important issue in stem cell biology relates to mechanisms of cellular
      plasticity. Specifically, could any observed multipotency of, e.g., adult stem
      cells arise from true transdifferentiation or as a result of cell-cell fusion? We
      studied this issue using a culture paradigm of astrocyte monolayers and
      multipotent neurospheres generated from neonatal cerebellar cortex and the
      subventricular zone (SVZ). Based on fluorescence in situ hybridization (FISH),
      cells from these cultures were found to contain an abnormal number of sex
      chromosomes, suggesting that cellular fusion is a common in vitro occurrence. A
      Cre/lox recombination method was also exploited to further confirm the evidence
      of fusion. Next, we assessed the potential of fusogenic microglial involvement by
      combining CD11b immunolabeling with FISH sex chromosome analysis. Differentiating
      neurospheres were also studied from the PU.1 knockout mouse that lacks cells of
      myeloid origin, presumed to be a source of central nervous system microglia. Very
      few cells immunopositive for the microglial marker CD11b were found to be
      aneuploid, and there was no difference in fusion frequency between PU.1+/+ and
      PU.1-/- neurospheres. These results, together, suggest that stem and/or
      progenitor cells that generate neurons and glia in culture possess the ability to
      generate fused polyploidal cells, but microglial participation is not a
      requirement for fusion to occur. In addition to caution that should be exerted
      during the interpretation of in vitro neural cell plasticity, the data also
      suggest that novel therapeutic treatments could be designed that exploit cellular
      fusion in rescue paradigms for degenerating neuronal populations.

PMID- 16406351
TI  - Behavioral seizure correlates in animal models of epilepsy: a road map for assay
      selection, data interpretation, and the search for causal mechanisms.
AB  - A broad spectrum of learning/memory, social interaction, and affective behavioral
      measures serve as functional correlates for neurobiological changes in seizure
      prone animals as well as in epileptic clinical populations. The utility of such
      measures is demonstrated by their ability to distinguish anomalous
      characteristics in developing organisms predisposed to seizure onset, as well as
      to discriminate prior seizure history in organisms with established pathology.
      For instance, typical findings that generalize across species suggest that
      seizure-experienced organisms exhibit a variety of deficits in cognitive function
      as well as inappropriate social neglect and aggression. Behavioral testing
      batteries have also proven useful in assessing neural mechanisms for seizure
      induction, subcortical neural circuits, and neuropeptide modulators, for example,
      as well as in identifying neural pathology resulting from prior seizure activity.
      However, the wanton application of behavioral tests can also produce false
      positives in the identification of seizure-related disorders unless alternative
      performance and motivational hypotheses are discounted effectively. Accordingly,
      the present review attempts to provide the reader interested in behavioral
      phenotyping and characterization of seizure-prone rats and mice with a roadmap
      for rational selection, implementation, and interpretation of data from behavior
      assays while highlighting potential successes and pitfalls inherent in employing
      functional correlates of brain activity using animal models of epilepsy.

PMID- 16406352
TI  - Are we eating more than we think? Illegitimate signaling and xenohormesis as
      participants in the pathogenesis of obesity.
AB  - Resource utilization may represent a central force driving evolution. A tight
      link between sensing energy availability and managing energy acquisition and
      utilization constitutes a common feature among all organisms. While such a link
      was likely adaptive during prehistoric evolution, modern lifestyles may decouple
      perceived cues from actual energy availability so as to promote obesity in
      humans. A particular illegitimate signal is chronic stress, which may shift body
      phenotype to suit a more conservative state of energy management. In prehistoric
      times, such a response likely aided survival during periods of low resource
      availability. However, new sources of chronic stress have emerged that bear
      little relationship to contextual energy, which is generally abundant in the
      modern world. In addition, modern techniques of husbandry and agriculture can
      produce stress in the food chain, such that food itself can act as an
      illegitimate signal of chronic stress. Obese livestock and unusual fat profiles
      in farmed fish, meat, and eggs may reflect stress phenotypes. Consumers of
      stressed foods may sense those signals--a phenomenon known as xenohormesis--and
      assume the stressed phenotype. This maladaptive process may promote obesity by
      erroneously biasing hosts towards caloric accumulation in the context of energy
      abundance. Regional tissue accumulation of fat may indicate local tissue stress.
      Atherosclerosis may result from stress signals that induce sympathetic bias and
      regional fat accumulation in vessel adventitia. Medications such as neuroleptics
      and foods such as diet drinks may generate illegitimate signals by mimicking
      molecules used for energy management. Implications for the prevention and
      treatment of dysfunctions related to these derangements are discussed. New
      strategies for manufacturing biologics by manipulating stress conditions or
      controlling fatty acid attachments to proteins are envisioned.

PMID- 16406353
TI  - When normal is not: the dilemma of interpreting laboratory averages of bioactive
      molecules subject to heterogeneous regulatory feedback and epigenetic mosaicism.
AB  - Complex regulatory systems control the levels of many bioactive molecules in the
      serum. These systems involve the integration of feedback responses from numerous
      tissues. End-organs and tissues can manifest epigenetic mosaicism, particularly
      with aging or disease states. We propose that an isolated lab value may reflect a
      blended average of inhomogeneous feedback responses from target tissues in
      various states of dysfunction. Reliance on such data may underestimate the state
      of systemic dysfunction. Yet in clinical practice, normal serum levels of a given
      molecule and its associated regulatory machinery are often assumed to reflect
      normal body homeostasis and tissue function. Organism-wide integration of
      abnormally high and low levels of bioactivity of a molecule in different tissues
      may yield apparently normal serum values of the bioactive molecule and known
      components of its regulatory system. We specifically discuss thyroid hormone
      regulation and function as a case example. Epigenetic reprogramming of either
      regulatory loops or tissue responses represents another way in which normal serum
      levels of the molecule may obscure target-organ dysfunction. The proposed idea
      has broad implications for disease pathogenesis, diagnosis, and therapies. A
      model where individual tissues employ illegitimate signaling to subvert the
      concerns of the organism as a whole is also proposed.

PMID- 16406354
TI  - Could zinc be protective against bronchiolitis obliterans?

PMID- 16406355
TI  - Trypanosoma cruzi: Impact of dual-clone infections on parasite biological
      properties in BALB/c mice.
AB  - Herein, we have analyzed major biological properties following dual-clone
      Trypanosoma cruzi infections in BALB/c mice. Eight T. cruzi clonal stocks, two of
      each principal genotype, including genotype 19 and 20 (T. cruzi I), hybrid
      genotype 39 (T. cruzi) and 32 (T. cruzi II) were combined into 24 different dual
      clone infections. Special attention was given to characterize biological
      parameters assayed including: prepatent period, patent period, maximum of
      parasitemia, day of maximum parasitemia, area under the parasitemia curve,
      infectivity, mortality, and hemoculture positivity. Our findings clearly
      demonstrated that features resultant of dual-clone infections of T. cruzi clonal
      stocks did not display either the characteristics of the corresponding monoclonal
      infections or the theoretical mixture based on the respective monoclonal
      infections. Significant changes in the expected values were observed in 4.2-79.2%
      of the mixtures considering the eight biological parameters studied. A lower
      frequency of significant differences was found for mixtures composed by
      phylogenetically distant clonal stocks. Altogether, our data support our
      hypothesis that mixed T. cruzi infections have a great impact on the biological
      properties of the parasite in the host and re-emphasizes the importance of
      considering the possible occurrence of natural mixed infections in humans and
      their consequences on the biological aspects of ongoing Chagas' disease.

PMID- 16406356
TI  - Screening of entomopathogenic Metarhizium anisopliae isolates and proteomic
      analysis of secretion synthesized in response to cowpea weevil (Callosobruchus
      maculatus) exoskeleton.
AB  - Cowpea crops are severely attacked by Callosobruchus maculatus, a Coleopteran
      that at the larval stage penetrates into stored seeds and feeds on cotyledons.
      Cowpea weevil control could be based in utilization of bacteria and fungi to
      reduce pest development. Entomopathogenic fungi, such as Metarhizium anisopliae,
      are able to control insect-pests and are widely applied in biological control.
      This report evaluated ten M. anisopliae isolates according to their virulence,
      correlating chitinolytic, proteolytic and alpha-amylolytic activities, as well
      proteomic analysis by two dimensional gels of fungal secretions in response to an
      induced medium containing C. maculatus shells, indicating novel biotechnological
      tools capable of improving cowpea crop resistance.

PMID- 16406357
TI  - Estrogens counteract the masculinizing effect of tributyltin in zebrafish.
AB  - Recently, it has been demonstrated that the biocide tributyltin (TBT) can
      interfere with fish sex differentiation, leading to a bias of sex toward males.
      On the contrary, it is well known that estrogenic compounds can induce fish
      feminization. Yet, the combined effects of mixtures of androgenic and estrogenic
      compounds on fish sex differentiation have never been investigated before, even
      though in the environment animals are frequently exposed to both groups of
      xenobiotics. Therefore, in order to investigate whether exposure to estrogenic
      compounds can block the masculinizing effect of TBT, 5 days post-fertilization
      zebrafish (Danio rerio) larvae were exposed for a four month period to TBT and to
      the synthetic estrogen-ethinylestradiol (EE2). The fish were fed a diet
      containing TBT at nominal concentrations of 25 and 100 ng TBT/g, and two groups
      of animals were also dosed with TBT plus EE2 at nominal water concentration of
      3.5 ng/L, using a flow-through design. As expected, fish exposed to TBT showed a
      bias of sex toward males (62.5% males in control tanks and 86% and 82% in TBT 25
      and TBT 100 ng TBT/g, respectively). Co-exposure to EE2 completely blocked the
      masculinizing effect of TBT, with 7% males in the TBT 25 ng/g + EE2 treatment and
      0% in the EE2 alone and in the TBT 100 ng/ + EE2 exposed groups. These results
      clearly indicate that EE2, at environmentally relevant concentrations, can block
      the TBT masculinizing effects in zebrafish, which suggests that in the aquatic
      environment the presence of estrogens may neutralize the fish masculinizing
      effect of TBT. Our findings highlight the need of testing the combined effects of
      contaminants, as single exposure studies may not be sufficient to predict the
      effects of mixtures of xenobiotics with antagonistic properties.

PMID- 16406358
TI  - Fatal toxoplasmosis and concurrent Calodium hepaticum infection in Korean
      squirrels (Tanias sibericus).
AB  - Four Korean squirrels (Tanias siberius) imported in Spain from People's Republic
      of China died 2 days after their arrival at a pet shop. They had neurological
      signs associated with generalized toxoplasmosis involving brain, lungs, liver,
      and the heart. Toxoplasma gondii-like tachyzoites and tissue cysts were found in
      organs of all four squirrels. The protozoa stained positively with T. gondii
      polyclonal antibodies and were ultrastructurally similar to T. gondii. Calodium
      (Capillaria) hepaticum infection was found in the liver of one squirrel.

PMID- 16406360
TI  - Acute toxicity and diuretic studies of Rungia repens aerial parts in rats.
AB  - Ethanolic extract of Rungia repens aerials parts (300 and 600 mg/kg p.o) showed
      diuretic activity in rats. The acute toxicity, orally evaluated in mice, was
      found to be higher than 3000 mg/kg.

PMID- 16406359
TI  - Grain legume proteins and nutraceutical properties.
AB  - Grain legumes are a valuable source of food proteins. Their exploitation is
      expected to grow in relation of a growing world's food needs. Moreover, it is
      currently taking place a reappraisal of the beneficial effects of legume seed
      dietary intake, which are the basis for various health claims. Proteins and
      peptides concur to the observed biological activities of legume seeds, but their
      effect(s) has(ve) not completely been disclosed. Aims of this review are: to
      report the most relevant putative positive effects of grain legumes on human
      health and to give an account of the current knowledge on the demonstrated legume
      seed protein biological activities. Specific effects on the prevention and
      treatment of various diseases, mostly of which are typical of the affluent
      countries, are reported. Examples of studies at molecular level aimed at
      elucidating of the underlying mechanism(s) are given. The prospects on targeted
      legume protein exploitation in the nutraceutical area, including the
      biotechnological approaches, are also considered.

PMID- 16406361
TI  - Antioxidant activity of polyphenols from solid olive residues of c.v. Coratina.
AB  - The antioxidant profile of extracts from solid olive residue (SOR) of c.v.
      Coratina, a cultivar widely diffused in the south of Italy, using both cell-free
      and cell-based experimental models, was investigated. A total hydroalcoholic
      extract (polyphenols content 19.7%) and a purified extract (Oleaselecttrade mark)
      (polyphenols content 35.1%) were tested for their ability to quench the stable
      free radical DPPH, the peroxyl radicals (ORAC assay), by monitoring the loss in
      fluorescence of R-phycoerythrin induced by the peroxyl radical generator AAPH and
      their ability to inhibit the cumene hydroperoxide-induced lysis of rat red blood
      cells (RBC). The total hydroalcoholic extract showed IC(50) 26.96+/-1.53
      microg/ml in the DPPH assay, that 10 microg/ml were equivalent to 2.11+/-0.12
      microg/ml Trolox (ORAC assay) and IC(50) 1.7+/-0.20 microg/ml in the RBC
      hemolysis. The Oleaselect extract was 4 to 5 folds more active than the
      hydroalcoholic extract in all the experimental models, with IC(50) values of
      7.36+/-0.38 microg/ml in the DPPH test and of 0.38+/-0.03 microg/ml in RBC; the
      antioxidant activity in the ORAC assay was slightly greater than that of Trolox
      (10 microg/ml equivalent to 11.45+/-0.40 microg/ml). The scavenging effect of the
      extract in the ORAC assay was compared to that of verbascoside (the main
      polyphenol component) and of caffeic acid (the basic constituent of
      verbascoside): the results indicate that caffeic acid (10 microg/ml equivalent to
      35.70+/-2.95 microg/ml Trolox) is more potent than verbascoside (10 microg/ml
      equivalent to 15.42+/-1.21 microg/ml Trolox) in entrapping peroxyl radicals.
      Finally the antioxidant activity of the Oleaselect extract was confirmed in human
      umbilical endothelial cells (EC) exposed to the site-specific peroxyl radical
      inducer AAPH, where a massive lipid peroxidation process (marker the fluorescence
      probe BODIPY) takes place, paralleled by a marked loss of cell viability (calcein
      assay). The purified extract (1-20 microg/ml) pre-incubated with EC for 1 h dose
      dependently inhibited both the lipid-peroxidation damage and cell death. Taking
      into account the total polyphenol content, these results clearly indicate a
      greater antioxidant activity for the purified extract, due to a cooperative
      antioxidant interaction among its polyphenol constituents.

PMID- 16406362
TI  - Pregnancy-induced modulation of calcium mobilization and down-regulation of Rho
      kinase expression contribute to attenuated vasopressin-induced contraction of the
      rat aorta.
AB  - Normal pregnancy is characterized by attenuated vascular reactivity to a variety
      of contractile agonists and this, in part, has been attributed to increased
      circulating vasodilators and/or impaired Ca(2+)-influx through L-type Ca(2+)
      channels. Our hypothesis in this study was that reduced Ca(2+)-dependent (influx)
      and Ca(2+)-independent (involving the RhoA/Rho-kinase pathway) mechanisms
      contributed to attenuated vasopressin-induced contraction of the pregnant rat
      aorta. AVP (10(-10) -3 x 10(-7) M) induced concentration-dependent contraction of
      aortic ring segments from nonpregnant and pregnant rats with no significant
      change in pD(2) values (8.53+/-0.11 and 8.33+/-0.18 in nonpregnant and pregnant
      rats, respectively). The maximum response was however significantly reduced in
      aorta segments from pregnant rats. Nifedipine (10(-6) M) significantly inhibited
      AVP-induced contraction in artery segments from nonpregnant but not pregnant rats
      indicating a reduced role for Ca(2+)-influx through L-type Ca(2+)-channels in AVP
      induced contractions of the pregnant rat aorta. Western blot analysis revealed
      the expression of ROCK-1 and ROCK-II isoforms in aorta segments from both groups.
      There was a significant reduction in the expression of ROCK-1 and ROCK-II
      isoforms in aortic tissues from pregnant rats. This is consistent with the
      reduced potency of Y-27632 in inhibiting AVP (10(-7) M) induced contraction in
      aorta segments from pregnant rats. It was concluded that pregnancy-induced
      attenuated vascular response to AVP was due to decreased Ca(2+)-influx through L
      type Ca(2+)-channels and decreased sensitization of the contractile myofilaments
      to Ca(2+).

PMID- 16406363
TI  - Yeast ABC transporters-- a tale of sex, stress, drugs and aging.
AB  - Yeast ATP-binding cassette (ABC) proteins are implicated in many biological
      phenomena, often acting at crossroads of vital cellular processes. Their
      functions encompass peptide pheromone secretion, regulation of mitochondrial
      function, vacuolar detoxification, as well as pleiotropic drug resistance and
      stress adaptation. Because yeast harbors several homologues of mammalian ABC
      proteins with medical importance, understanding their molecular mechanisms,
      substrate interaction and three-dimensional structure of yeast ABC proteins might
      help identifying new approaches aimed at combating drug resistance or other ABC
      mediated diseases. This review provides a comprehensive discussion on the
      functions of the ABC protein family in the yeast Saccharomyces cerevisiae.

PMID- 16406364
TI  - First "hybrid" ligands of vanilloid TRPV1 and cannabinoid CB2 receptors and non
      polyunsaturated fatty acid-derived CB2-selective ligands.
AB  - 12-Phenylacetyl-ricinoleoyl-vanillamide (phenylacetylrinvanil, PhAR, IDN5890), is
      an ultra-potent agonist of human vanilloid TRPV1 receptors also endowed with
      moderate affinity for human cannabinoid CB(2) receptors. To improve its CB(2)
      affinity and temper its potency at TRPV1, the modification of the polar headgroup
      and the lipophilic 12-acylgroup of PhAR was pursued. Replacement of the vanillyl
      headgroup of PhAR with various aromatic or alkyl amino groups decreased activity
      at TRPV1 receptors, although the dopamine, cyclopropylamine, 1'-(R)- and 1'-(S)
      methyl-ethanolamine, and ethanolamine derivatives retained significant potency
      (EC(50) 31-126 nM). Within these compounds, the 12-phenylacetylricinoleyl
      cyclopropylamide and ethanolamide were the strongest ligands at CB(2) receptors,
      with K(i) of 22 and 44 nM, and 14- and >20-fold selectivity over cannabinoid
      CB(1) receptors, respectively. The propyl- and allyl-derivatives also exhibited
      high affinity at CB(2) receptors (K(i)=40 and 22 nM, with 40 and >80-fold
      selectivity over CB(1) receptors, respectively), but no activity at TRPV1
      receptors. The cyclopropyl- and allyl-derivatives behaved as CB(2) inverse
      agonists in the GTP-gamma-S binding assay. Addition of para-methoxy, -tert-butyl
      or -chlorine groups to the 12-phenylacetyl moiety of PhAR produced compounds that
      retained full potency at TRPV1 receptors, but with improved selectivity over
      CB(2) or CB(1) receptors. Thus, the manipulation of PhAR led to the development
      of the first CB(2)/TRPV1 dual ligands and of an entirely new class of inverse
      agonists at CB(2) receptors. Both types of compounds might find application in
      the treatment of inflammation, and represent new molecular probes to investigate
      the endocannabinoid-endovanilloid signalling system.

PMID- 16406365
TI  - Inverted repeat domains in membrane proteins.
AB  - With the upsurge in known membrane protein structures, common structural themes
      have started to emerge. One of these is the inverted repeat, a tandem of alpha
      helical domains that have similar tertiary folds but opposite membrane
      orientations. In all previously known examples, both repeat units were encoded in
      a single continuous polypeptide. Recent structures of a bacterial multidrug
      transporter, EmrE, revealed an inverted repeat membrane protein wherein the two
      repeat units are assembled from two polypeptides with the same primary sequence.
      Here, we speculate on some of the implications of the EmrE structure with regards
      to our understanding of membrane protein evolution and topogenesis.

PMID- 16406366
TI  - Sjl2p is specifically involved in early steps of endocytosis intimately linked to
      actin dynamics via the Ark1p/Prk1p kinases.
AB  - Sjl2p is one of three yeast phosphoinositide 5'-phosphatases that belong to the
      conserved family of synaptojanins. Here, we show that Sjl2p is specifically
      associated with cortical actin patches which aggregate upon loss of the actin
      regulating kinases Ark1p and Prk1p. The Sjl2p-containing clumps overlap with
      clathrin and early endocytic structures generated independently of NSF/Sec18p,
      but not with endosome- and trans Golgi network-derived membranes. Consistent with
      the finding that Sjl2p can bind to clathrin heavy chain in vitro, our results
      suggest that Sjl2p localizes to smooth endocytic vesicles that may be derived
      from clathrin-coated structures.

PMID- 16406367
TI  - High expression of N-acetylglucosaminyltransferase V in favorable neuroblastomas:
      Involvement of its effect on apoptosis.
AB  - Neuroblastoma (NBL), derived from the sympathetic precursor cells, is one of the
      most common pediatric solid tumors. The expression of N
      acetylglucosaminyltransferase V and IX (GnT-V and GnT-IX) mRNA in 126 primary
      NBLs were quantitatively analyzed and higher expression levels of GnT-V were
      found to be associated with favorable stages (1, 2 and 4s). Conversely, the
      downregulation of GnT-V expression by small interfering RNA resulted in a
      decrease in the susceptibility to cell apoptosis induced by retinoic acid in NBL
      cells accompanied by morphological change. These results suggest that GnT-V is
      associated with prognosis by modulating the sensitivity of NBLs to apoptosis.

PMID- 16406368
TI  - Functional expression of the taste-modifying protein, miraculin, in transgenic
      lettuce.
AB  - Taste-modifying proteins are a natural alternative to artificial sweeteners and
      flavor enhancers and have been used in some cultures for centuries. The taste
      modifying protein, miraculin, has the unusual property of being able to modify a
      sour taste into a sweet taste. Here, we report the use of a plant expression
      system for the production of miraculin. A synthetic gene encoding miraculin was
      placed under the control of constitutive promoters and transferred to lettuce.
      Expression of this gene in transgenic lettuce resulted in the accumulation of
      significant amounts of miraculin protein in the leaves. The miraculin expressed
      in transgenic lettuce possessed sweetness-inducing activity. These results
      demonstrate that the production of miraculin in edible plants can be a good
      alternative strategy to enhance the availability of this protein.

PMID- 16406369
TI  - GG: a domain involved in phage LTF apparatus and implicated in human MEB and non
      syndromic hearing loss diseases.
AB  - Here, we report the identification of a novel domain--GG (domain in KIAA1199,
      FAM3, POMGnT1 and Tmem2 proteins, with two well-conserved glycine residues),
      present in eukaryotic FAM3 superfamily (FAM3A, FAM3B, FAM3C and FAM3D), POMGnT1
      (protein O-linked mannose beta-1,2-N-acetylglucosaminyltransferase), TEM2
      proteins as well as phage gp35 proteins. GG domain has been revealed to be
      implicated in muscle-eye-brain disease and non-syndromic hearing loss. The
      presence of GG domain in Bacteriophage gp35 hinge connector of long tail fiber
      might reflect the horizontal gene transfer from organisms. And we proposed that
      GG domain might function as important structural element in phage LTF.

PMID- 16406370
TI  - Paediatric burns in Kuwait: incidence, causes and mortality.
AB  - From a prospective study on burn patients admitted at the Burn Center in Kuwait
      during 1993-2001, 826 paediatric burn cases, in 0-14 years age group, were
      retrieved to study incidence, causes, and mortality among children. The
      demographic characteristics, clinical features, and outcome constituted our data
      file in Statistical Software, SPSS. Overall incidence rate was 17.5/100,000
      children aged 0-14 years, being almost twice (34/100,000) among those between 0
      and 4 years, constituting 70.8% of all paediatric burns. Scald was the main cause
      of burn (67%), followed by flame (23%). Mean age (6.4 years) of children with
      flame burns, was significantly higher (p < 0.001) than those with scalds, or
      other causes. A positive significant correlation existed between duration of
      hospital stay and TBSA% (r = 0.56, p < 0.001). Overall mortality rate was
      0.23/100,000 children, maximum (0.52/100,000) being in children below 5 years.
      Among 11 (1.3%) non-survivors, flame burns caused nine fatalities. Multiple
      logistic regression mooring predicted children aged < 5 years, flame burns and
      TBSA >or= 70%, (OR = 29.2, p < 0.001), as main contributing factors to fatal
      outcome among children. Gender and nationality had no influence on incidence or
      mortality. These findings will hopefully stimulate development of targeted and
      sustainable interventions for reducing burns occurrence among identified
      paediatric high-risk groups.

PMID- 16406371
TI  - Dominance behaviour and regulation of foraging in the primitively eusocial wasp
      Ropalidia marginata (Lep.) (Hymenoptera: Vespidae).
AB  - Ropalidia marginata is a primitively eusocial, polistine wasp widely distributed
      in peninsular India. In spite of its primitively eusocial status, queens of R.
      marginata are surprisingly docile and behaviourally non-dominant (except during
      the first week or so of their careers as queens). Yet they successfully maintain
      reproductive monopoly throughout their careers, probably through the use of
      pheromones. Workers exhibit dominance-subordinate interactions but these
      behaviours are not involved in regulating reproductive competition among the
      workers because workers with high dominance ranks are not necessarily the ones
      who replace lost queens. We have speculated and provided correlational evidence
      before that dominance-subordinate interactions among the workers have been co
      opted in this species for the workers to regulate each other's foraging. Here, we
      provide experimental evidence in support of the speculation, by reducing demand
      for food and showing that this results in a significant decrease in the frequency
      of dominance-subordinate interactions among the workers.

PMID- 16406372
TI  - Facultative virulence: a strategy to manipulate host behaviour?
AB  - Examples of behavioural manipulation by parasites are numerous, but the processes
      underlying these changes are not well characterized. From an evolutionary point
      of view, behavioural changes in infected hosts have often been interpreted as
      illustrations of the extended phenotype concept, in which genes in one organism
      (the parasite) have phenotypic effects on another organism (the host). Here, we
      approach the problem differently, suggesting that hosts, by cooperating with
      manipulative parasites rather than resisting them, might mitigate fitness costs
      associated with manipulation. By imposing extra fitness costs on their hosts in
      the absence of compliance, parasites theoretically have the potential to select
      for cooperative behaviour by their hosts. Although this 'mafia-like' strategy
      remains poorly documented, we believe that it has substantial potential to
      resolve issues specific to the evolution of behavioural alterations induced by
      parasites.

PMID- 16406373
TI  - Timing, memory for intervals, and memory for untimed stimuli: The role of
      instructional ambiguity.
AB  - Theories of animal timing have had to account for findings that the memory for
      the duration of a timed interval appears to be dramatically shorted within a
      short time of its termination. This finding has led to the subjective shortening
      hypothesis and it has been proposed to account for the poor memory that animals
      appear to have for the initial portion of a timed interval when a gap is inserted
      in the to-be-timed signal. It has also been proposed to account for the poor
      memory for a relatively long interval that has been discriminated from a shorter
      interval. I suggest here a simpler account in which ambiguity between the gap or
      retention interval and the intertrial interval results in resetting the clock,
      rather than forgetting the interval. The ambiguity hypothesis, together with a
      signal salience mechanism that determines how quickly the clock is reset at the
      start of the intertrial interval can account for the results of the reported
      timing experiments that have used the peak procedure. Furthermore, instructional
      ambiguity rather than memory loss may account for the results of many animal
      memory experiments that do not involve memory for time.

PMID- 16406374
TI  - Social partner preferences of male and female fighting fish (Betta splendens).
AB  - While the social interactions of Betta splendens have been studied in the
      contexts of dominance hierarchies, mate choice and communication networks, the
      social partner preferences of Betta have been largely overlooked. In this study,
      we presented male and female Betta with a single male, a single female, and a
      group of three females in dichotomous choice tests in order to better understand
      basic social interactions in this largely nonsocial species. The highly
      territorial Betta preferred associating with conspecifics in nearly every
      configuration we tested, with exceptions noted when single females were given the
      choice between a lone male and an empty chamber, and when males were presented
      with a single female and an empty chamber. Also, in most tests, the fish chose to
      spend more time with the larger group of females. The motivation for this
      preference certainly varied from reproductive to anti-predator. While such
      behavior might not suggest true shoaling behavior, it does demonstrate a subtle
      degree of sociality.

PMID- 16406375
TI  - Appetitive latent inhibition in rats: preexposure performance does not predict
      conditioned performance.
AB  - Nonreinforced preexposure to a conditioned stimulus impairs subsequent
      conditioning with that stimulus. The goal of these studies was to assess the
      extent to which acquisition performance could be predicted from preexposure
      performance using a correlational approach. For both preexposure and autoshaping,
      four measures of performance were computed, including overall average lever
      pressing, lever pressing in the initial session, percentage change in lever
      pressing, and slopes. These measures were correlated in a large sample of rats
      trained in an autoshaping situation. None of the three measures of autoshaping
      performance was consistently predicted by any of the three measures of
      preexposure performance. These results are consistent with the view that latent
      inhibition is not reducible to long-term habituation.

PMID- 16406376
TI  - Effects of prefeeding, intercomponent-interval food, and extinction on temporal
      discrimination and pacemaker rate.
AB  - This experiment investigated the effects of nonpharmacological disruption on
      temporal discrimination. Pigeons responded on a multiple schedule composed of
      fixed interval, color-matching, and temporal-discrimination components. The
      effects of three different disruptors (prefeeding, intercomponent-interval food,
      and extinction) were assessed. All disruptors decreased response rates during the
      fixed interval. Prefeeding and intercomponent-interval food had unsystematic
      effects on response patterning during the fixed interval, whereas extinction
      increased the relative response rate in the initial portions of the fixed
      interval. Accuracy of color matching was decreased by prefeeding and was not
      systematically affected by intercomponent-interval food and extinction. In the
      temporal-discrimination component, all disruptors flattened the psychophysical
      functions relating proportion long responses to sample duration. This result
      indicates a general disruption of temporal discrimination. In addition, parameter
      estimates derived from the behavioral theory of timing indicated all disruptors
      decreased pacemaker rate, a result consistent with the predictions of the theory.
      These results highlight the similarities between disruption of temporal
      discrimination by pharmacological and nonpharmacological manipulations.

PMID- 16406377
TI  - Responses of the diaphragm to transcranial magnetic stimulation during wake and
      sleep in humans.
AB  - The human ventilation depends on bulbospinal and corticospinal commands. This
      study assessed their interactions in five healthy volunteers (two men, age 25-35)
      through the description of diaphragm and abductor pollicis brevis (APB) motor
      potentials (DiMEPs, abpMEPs) evoked by transcranial magnetic stimulation (TMS)
      during relaxed expiration and tidal inspiration and during wake and sleep. NREM
      decreased corticospinal excitability and REM further did so, for both the
      diaphragm and the APB. During wake, inspiration shortened supine DiMEPs latencies
      (expiration 18.56+/-1.90ms; inspiration 17.37+/-1.48ms, P<0.001). This persisted
      during sleep in an augmented manner (expiration: 21.05+/-1.39ms; inspiration
      18.69+/-1.17ms, P=0.002). Inspiration had no effect on apbMEPs during wake and
      sleep. IN CONCLUSION: (1) the tidal bulbospinal input to phrenic motoneurones is
      sufficient to modulate the throughput of the corticospinal pathway to these
      neurones; (2) this modulation is best seen after the sleep related removal of
      corticospinal and/or afferent inputs.

PMID- 16406379
TI  - Thirsty heroin addicts show different fMRI activations when exposed to water
      related and drug-related cues.
AB  - Relapse to drug use is frequently preceded or caused by craving, an intense
      desire for drug. Advances in functional brain imaging techniques make it possible
      to directly investigate this special mental state in vivo and non-invasively.
      Extant imaging studies on craving have been mostly on cocaine which is the
      dominant drug abused in the U.S. Employing functional MRI, we examined substance
      specificity of the neural circuitry underlying craving for heroin. Heroin is the
      primary drug abused in south-east Asia and has, particularly, become a serious
      social problem for China in recent years. Following abstinence from water and
      drug, 14 active heroin addicts (all male, mean age 33.2 years, average drug use
      history 7.1 years) underwent scanning inside a 1.5T Philips MR scanner during
      exposure to water-related, drug-related, and neutral cues. Water-related cues
      elicited anterior cingulate activation (Brodmann's area BA 32/24). Drug-related
      cues activated bilateral inferior frontal cortex (BA 44/45), confirming the
      critical role of prefrontal cortex in drug craving. Results suggest heroin
      craving may involve different neural substrates than do desire from basic
      physiological drives, such as thirst. As the first fMRI study of heroin craving,
      our study adds to the scant but much-needed brain imaging literature on heroin
      addiction.

PMID- 16406378
TI  - Cloning and sequence analysis of pituitary prolactin cDNA from the northern brown
      bandicoot (Isoodon macrourus).
AB  - The nucleotide sequence for pituitary prolactin cDNA from the marsupial bandicoot
      (Isoodon macrourus) was determined by reverse transcription-polymerase chain
      reaction and 5'/3' rapid amplification of cDNA ends. The deduced amino acid
      sequence showed high sequence identity with brushtail possum prolactin (95%) and
      all of the expected structural features of a quadruped prolactin. A prolactin
      gene tree was constructed and rates of evolution calculated for bandicoot,
      possum, opossum and several mammalian and non-mammalian prolactins. Bootstrap
      analysis provided strong support for marsupials as a sister group with eutherian
      mammals and weak support for opossum and bandicoot as an independent grouping
      from the brushtail possum. The rates of molecular evolution for marsupial
      prolactins were comparable to the slow rate seen in the majority of quadruped
      prolactins that have been sequenced.

PMID- 16406380
TI  - Ion-pair reversed-phase HPLC: assay validation of sodium tanshinone IIA sulfonate
      in mouse plasma.
AB  - Sodium tanshinone IIA sulfonate (STS), a hydrophilic ionic substance, is used as
      a cardiovascular drug. An ion-pair reversed-phase high-performance liquid
      chromatography (IP-RP-HPLC) method for the determination of STS in mouse plasma
      was initially developed. The assay involved a rapid and simple extraction process
      and subsequent detection at 271 nm. The retention time for STS was 7.5 min. Based
      on extracted STS standard mouse plasma at 1.5,10 and 50 microg/ml, the assay
      precision were 2.7, 2.1 and 1.7% with a mean accuracy of 96.7, 98.5 and 99.4%,
      respectively. At plasma concentration of 1.5, 50 and 75 microg/ml, the mean
      recovery of STS were 93.1, 96.3 and 97.5%. The limit of detection (LOD) and limit
      of quantification (LOQ) for STS was 0.1 microg/ml and 0.5 microg/ml,
      respectively. Linear responses were observed over a wide concentration range (0.5
      100 microg/ml) for STS in mouse plasma. STS can be detected after intravenous
      administration. This method was performed for the first time in pharmacokinetic
      studies of STS in the mouse.

PMID- 16406381
TI  - Signaling through the phosphatidylinositol 3-kinase regulates mechanotaxis
      induced by local low magnetic forces in Entamoeba histolytica.
AB  - In micro-organisms, as well as in metazoan cells, cellular polarization and
      directed migration are finely regulated by external stimuli, including mechanical
      stresses. The mechanisms sustaining the transduction of such external stresses
      into intracellular biochemical signals remain mainly unknown. Using an external
      magnetic tip, we generated a magnetic field gradient that allows migration
      analysis of cells submitted to local low-intensity magnetic forces (50 pN). We
      applied our system to the amoeba Entamoeba histolytica. Indeed, motility and
      chemotaxis are key activities that allow this parasite to invade and destroy the
      human tissues during amoebiasis. The magnetic force was applied either inside the
      cytoplasm or externally at the rear pole of the amoeba. We observed that the
      application of an intracellular force did not affect cell polarization and
      migration, whereas the application of the force at the rear pole of the cell
      induced a persistent polarization and strongly directional motion, almost
      directly opposed to the magnetic force. This phenomenon was completely abolished
      when phosphatidylinositol 3-kinase activity was inhibited by wortmanin. This
      result demonstrated that the applied mechanical stimulus was transduced and
      amplified into an intracellular biochemical signal, a process that allows such
      low-intensity force to strongly modify the migration behavior of the cell.

PMID- 16406382
TI  - alpha-Neurexins are required for efficient transmitter release and synaptic
      homeostasis at the mouse neuromuscular junction.
AB  - Neurotransmission at chemical synapses of the brain involves alpha-neurexins,
      neuron-specific cell-surface molecules that are encoded by three genes in
      mammals. Deletion of alpha-neurexins in mice previously demonstrated an essential
      function, leading to early postnatal death of many double-knockout mice and all
      triple mutants. Neurotransmitter release at central synapses of newborn knockouts
      was severely reduced, a function of alpha-neurexins that requires their
      extracellular sequences. Here, we investigated the role of alpha-neurexins at
      neuromuscular junctions, presynaptic terminals that lack a neuronal postsynaptic
      partner, addressing an important question because the function of neurexins was
      hypothesized to involve cell-adhesion complexes between neurons. Using systems
      physiology, morphological analyses and electrophysiological recordings, we show
      that quantal content, i.e. the number of acetylcholine quanta released per nerve
      impulse from motor nerve terminals, and frequency of spontaneous miniature
      endplate potentials at the slow-twitch soleus muscle are reduced in adult alpha
      neurexin double-knockouts, consistent with earlier data on central synapses.
      However, the same parameters at diaphragm muscle neuromuscular junctions showed
      no difference in basal neurotransmission. To reconcile these observations, we
      tested the capability of control and alpha-neurexin-deficient diaphragm
      neuromuscular junctions to compensate for an experimental reduction of
      postsynaptic acetylcholine receptors by a compensatory increase of presynaptic
      release: Knockout neuromuscular junctions produced significantly less
      upregulation of quantal content than synapses from control mice. Our data suggest
      that alpha-neurexins are required for efficient neurotransmitter release at
      neuromuscular junctions, and that they may perform a role in the molecular
      mechanism of synaptic homeostasis at these peripheral synapses.

PMID- 16406384
TI  - Expansion and hydrodynamic properties of cellulose-stainless steel powder
      composite matrix for expanded bed adsorption.
AB  - For better understanding the influences of solid phase properties on the
      performance of the expanded bed, the expansion and hydrodynamic properties of
      cellulose-stainless steel powder composite matrix with a series of densities was
      investigated and analyzed in an expanded bed. Two kinds of matrix particle
      diameter fractions, the small one (60-125 microm) and the large (125-300 microm),
      were used in the present work. In general, the expansion factors decreased
      obviously with the increase of matrix density. A linear relation between the mean
      density of matrix and superficial velocity at expansion factor of 2.5 was found
      for same series of matrices. The Richardson-Zaki equation could correlate the bed
      expansion and operation fluid velocity for all matrices tested. The theoretical
      prediction of correlation parameters (the terminal settling velocity U(t) and
      expansion index n) was improved with the modification of equations in the
      literature. The residence time distributions were investigated to characterize
      the hydrodynamic property in expanded bed. Compared with three evaluation factors
      (the height equivalent of theoretical plate, Bo number and axial distribution
      coefficient D(ax)), the results indicated that D(ax) is the best parameter to
      analyze the bed stability of expanded bed under various operation conditions and
      matrix properties. In addition, it was found that fluid velocity is the most
      essential factor to influence the hydrodynamic properties in the bed. A linear
      relation between the D(ax) and superficial fluid velocity for all matrices tested
      was established.

PMID- 16406385
TI  - Implementation of a rapid and automated high performance liquid chromatography
      method development strategy for pharmaceutical drug candidates.
AB  - A comprehensive, fully automated strategy is demonstrated for HPLC-UV
      chromatographic method development using ChromSword optimization software. The
      strategy involves: (1) the automated screening of various column and mobile phase
      combinations, (2) rational selection of the best starting conditions; and (3)
      subsequent automated method development to generate optimized separation methods.
      Pharmaceutical compounds were applied to solve problematic drug impurity
      separations. ChromSword software automates the screening, optimization, and
      documentation steps thus reducing the method development time. The strategy was
      compared to a manual method development approach showing the automated method
      strategy affords better selectivity in a shorter time.

PMID- 16406383
TI  - The characterisation of E. coli O157:H7 isolates from cattle faeces and feedlot
      environment using PFGE.
AB  - The objectives of this study were to investigate the diversity of Escherichia
      coli O157:H7 isolates obtained over a 3-month period from a cattle feedlot in
      order to assess the relationship between environmental and faecal isolates and to
      determine the pattern of transmission of E. coli O157:H7 between groups of
      cattle. Faecal samples were obtained from cattle housed in four adjacent feedlot
      pens at monthly intervals, with environmental pen samples collected
      simultaneously. All E. coli O157:H7 isolates obtained were examined by pulsed
      field gel electrophoresis (PFGE), polymerase chain reaction (PCR) to detect eaeA,
      ehxA, stx1 and stx2 genes and antibiotic sensitivity profiling. Ten isolates were
      subjected to acid shock to imitate conditions in the acidic cattle abomasum and
      assess the effect on PFGE profiles. E. coli O157:H7 was isolated from 69 faecal
      samples and 26 environmental samples. All isolates (n=95) carried the genes for
      eaeA, ehxA and stx2 and were sensitive to all antibiotics tested. The PFGE
      profiles of all isolates differed by no more than two bands and clustered within
      80% similarity following dendrogram analysis. Acid shock had no effect on the
      subsequent PFGE patterns. A total of 8.7% (6/69) of cattle were shedding E. coli
      O157:H7 in the first month with faecal shedding increasing to 52% (36/69) by the
      third month of the study. A single isolate of E. coli O157:H7 may be passed
      rapidly through cattle pens, with the environment acting as a significant
      reservoir for transmission. PFGE is a useful tool for tracking the direct and
      indirect transmission of E. coli O157:H7 isolates on the farm.

PMID- 16406386
TI  - Inflammatory, autoimmune, chronic diseases: bad diet and physical inactivity are
      causes or effects?
AB  - It is now well established that most chronic diseases, especially those
      identified as inflammatory, are statistically correlated with some typical
      dietary excesses and physical inactivity. But do really these habits cause the
      diseases, or they result from them? Current opinion favours the first option, but
      fails to explain why the satisfaction of eating, naturally evolved in our brains
      to produce health, apparently induces countless millions of people to eat
      unrestrictedly until becoming mortally sick, whereas trying to keep a
      theoretically healthy diet is most often a real torture. The inverse explanation
      makes much more sense: since inflammation produces much heat, calorie-rich diets
      are required. An inflamed digestive tract lacks digestive power and is easily
      irritated or damaged by solid objects, therefore requiring a refined,
      concentrated, low-fibre diet. And inflamed or merely sick organisms are easily
      exhausted by physical effort, hence physical inactivity. This study confirms
      that, most probably, the primary causes of inflammatory diseases are always
      external inflammatory agents, like infectious micro-organisms or toxic
      substances, of which a particularly ubiquitous example is nicotine. High
      calorie/low-fibre diets and physical inactivity are direct consequences of
      generalised inflammation. Inversely, in most cases, physical exercise and
      moderation in eating, by themselves, cannot substantially suppress inflammations,
      but they can prevent them from being further reinforced by the neural reward
      system. Moreover, diets and exercise causing important suffering will usually do
      more harm than good, especially to children and young people, not to mention
      pregnant or nursing women. Only the identification and elimination of the
      inflammatory agents can efficiently prevent and cure inflammatory diseases, and
      currently nicotine, absorbed intentionally or passively, from tobacco or other
      sources, must be considered the chief suspect because of its inflammatory power,
      ubiquity and addictive properties.

PMID- 16406387
TI  - Humans are evolutionarily adapted to caloric restriction resulting from
      ecologically dictated dietary deprivation imposed during the Plio-Pleistocene
      period.
AB  - Humans are evolutionarily adapted to chronic undernutrition as a consequence of
      ecologically dictated dietary restriction. Increased aridity, cooler temperatures
      and increased climatic oscillation effected an alteration of the quantity and
      quality of vegetation upon which hominids depended for food during the Plio
      Pleistocene period. Hominids responded physiologically to climate-induced caloric
      curtailment in the same way organisms respond to experimentally imposed caloric
      restriction: by reducing the rate and/or altering the manner in which they
      metabolized fuel. Such metabolic alterations are mediated principally by the
      hypothalamus and it is herein hypothesized that the human hypothalamus was
      subjected to substantial selective pressure, promoting an energetically
      conservative hypometabolic state. Moreover, the most salient phenotypic
      characteristics typifying the human species - long lifespan, low reproductive
      potential, lengthy development and high brain/bodyweight ratio - are effectuated
      in organisms undergoing caloric restriction. These phenotypic/physiological
      characteristics - herein termed the quadripartite complex - can be modulated by
      metabolic rate, which is, in turn, modulated by the hypothalamus. An appreciable
      alteration in climate occurred between 2.0 and 1.5 million years ago, a juncture
      at which one hominid lineage (Paranthropus) went extinct. Paranthropus was
      characterized by such external adaptations as robust cranio-facial morphology and
      pronounced enamel deposition, indicative of subsistence on tough, low-quality
      vegetal foods. Conversely, the Homo lineage responded to its marginal dietary
      repertoire through internal means, centering on metabolic suppression. It is
      herein hypothesized that this adaptive metabolic alteration, enacted in response
      to ecologically imposed caloric restriction, produced the defining morphologic
      attributes of Homo and enabled the evolutionary success of the human species.
      Among the implications of this line of thinking is that modern humans may be
      particularly sensitive to the deleterious effects of excess energy intake and,
      concomitantly, particularly amenable to the ameliorative effects of caloric
      restriction.

PMID- 16406388
TI  - Fluconazole-induced hepatic cytochrome P450 gene expression and enzymatic
      activities in rats and mice.
AB  - This study was undertaken to examine the effects of the triazole antifungal agent
      fluconazole on the expression of hepatic cytochrome P450 (Cyp) genes and the
      activities of Cyp enzymes in male Sprague-Dawley rats and male CD-1 mice.
      Alkoxyresorufin O-dealkylation (AROD) methods were used as measures of Cyp enzyme
      activities. Western analyses identified specific Cyp isoforms. Quantitative real
      time reverse-transcription polymerase chain reaction (quantitative real time-RT
      PCR) assays were used to quantitate the mRNA expression of specific Cyp genes
      induced by this conazole. Rats and mice were administered fluconazole 2, 25, or
      50 mg/kg bw/d by gavage daily for 14 days. In rats, fluconazole treatment (50
      mg/kg bw/d) significantly induced pentoxyresorufin O-dealkylation (PROD),
      benzyloxyresorufin O-dealkylation (BROD), and ethoxyresorufin O-dealkylation
      (EROD) hepatic microsomal activities. Fluconazole treatment significantly
      increased rat hepatic mRNA expression of CYP2B1 and CYP3A23/3A1 with dose-related
      responses. The highest dose of fluconazole gave a 128-fold induction of CYP2B1
      and a 4.6-fold induction of CYP3A23/3A1 mRNA. CYP3A2 mRNA levels were also
      overexpressed 5.6-7.2-fold depending on dose. Western immunoblots of rat hepatic
      microsomal proteins identified Cyp isoforms: CYP1A1, CYP1A2, CYP2B1/2,
      CYP3A23/3A1, and Cyp3A2 with increased levels of CYP2B1/2 and CYP3A23/3A1
      proteins. In mice, fluconazole induced BROD, PROD, EROD, and methoxyresorufin O
      dealkylation hepatic microsomal activities after treatment with 25 and 50 mg/kg
      bw/d. Fluconazole increased mouse hepatic mRNA expression of Cyp2b10 (1.9-fold)
      and Cyp3a11 (2.6-fold) in the 50 mg/kg bw/d treatment group. In summary, these
      results indicated that fluconazole, a triazole-containing conazole, clearly
      induced CYP2B and CYP3A families of isoforms in rat liver and Cyp2b and Cyp3a
      families of isoforms in mouse liver.

PMID- 16406389
TI  - Role of trace elements in cadmium chloride uptake in hepatoma cell lines.
AB  - Cadmium coexists with other metals in various products. Releases of cadmium in
      the environment occur in parallel to the release of other metals including
      copper, iron and zinc which also have an essential role in human homeostasis as
      they participate in various biochemical pathways. We studied the interaction of
      iron, copper, zinc and calcium channel blockers (nifedipine and verapamil) with
      cadmium chloride in two hepatoma cell lines (HepG2 and HTC cells) in order to
      determine if these trace elements can affect CdCl(2) uptake and interfere with
      its toxicity. Both cell lines were initially exposed to CdCl(2) (0-200 microM)
      for 2h and the uptake of the metal was determined. Cadmium chloride uptake by
      HepG2 and HTC cells shows an increase with increasing doses of the metal. Cells
      were also pretreated with 100 uM of FeCl(2) or ZnCl(2) or CuCl(2) or with a
      nifedipine/verapamil (100 uM) mixture for 2h and then exposed to 200 uM CdCl(2)
      for 1h in the presence of the trace elements. The uptake of CdCl(2) was
      determined as well as the membrane integrity (LDH leakage assay), the cell
      viability (neutral red assay) and cell proliferation (protein assay). Zinc and
      calcium channel blockers inhibited the uptake of cadmium chloride by both cell
      lines. On the other hand iron loading resulted in increased uptake of CdCl(2) by
      both cell lines whereas copper loading increased the uptake of cadmium chloride
      from HTC cells and inhibited the uptake by HepG2 cells. These findings are of
      importance when the effects of cadmium on living organisms are examined since co
      exposure to cadmium and other metals can occur.

PMID- 16406390
TI  - Wettability of calcite and mica modified by different long-chain fatty acids (C18
      acids).
AB  - The effect of long-chain fatty acid adsorption on the wetting states of calcite
      and mica powders is investigated. The selected long-chain fatty acids are
      saturated or unsaturated aliphatic acids (stearic acid and oleic acid,
      respectively) and naphthenic acids with saturated or unsaturated aromatic rings
      (18-cyclohexyloctadecanoic acid and 18-phenoloctadecanoic acid, respectively).
      The amount of irreversibly adsorbed acid is determined by thermogravimetric
      analysis. The affinity of water and n-decane for these samples before and after
      modification is deduced from their adsorption isotherm and microcalorimetry.
      Thermodynamic analysis of surface pressure and spreading tension are performed
      based on adsorption isotherms. The enthalpy versus coverage curve for water
      adsorption and its comparison to liquefaction enthalpy is shown to be a
      meaningful method for characterizing the wettability of a surface. The naphthenic
      acid with unsaturated aromatic ring deeply modifies the calcite to an oil-wet
      state. The mica powder was not as strongly modified as calcite by these acid
      molecules.

PMID- 16406391
TI  - Prostate-specific antigen (PSA) bounce and other fluctuations: which biochemical
      relapse definition is least prone to PSA false calls? An analysis of 2030 men
      treated for prostate cancer with external beam or brachytherapy with or without
      adjuvant androgen deprivation therapy.
AB  - PURPOSE: To determine the false call (FC) rate for prostate-specific antigen
      (PSA) relapse according to nine different PSA relapse definitions after a PSA
      fluctuation (bounce) has occurred after external beam radiation therapy (EBRT) or
      brachytherapy, with or without adjuvant androgen deprivation therapy. METHODS AND
      MATERIALS: An analysis of a prospective database of 2030 patients was conducted.
      Prostate-specific antigen relapse was scored according to the American Society
      for Therapeutic Radiology and Oncology (ASTRO), Vancouver, threshold + n, and
      nadir + n definitions for the complete data set and then compared against a
      truncated data set, with data subsequent to the height of the bounce deleted. The
      FC rate was calculated for each definition. RESULTS: The bounce rate, with this
      very liberal definition of bounce, was 58% with EBRT and 84% with brachytherapy.
      The FC rate was lowest with nadir + 2 and + 3 definitions (2.2% and 1.6%,
      respectively) and greatest with low-threshold and ASTRO definitions (32% and 18%,
      respectively). The ASTRO definition was particularly susceptible to FC when
      androgen deprivation therapy was used with radiation (24%). DISCUSSION: New
      definitions of biochemical non-evidence of disease that are more robust than the
      ASTRO definition have been identified. Those with the least FC rates are the
      nadir + 2 and nadir + 3 definitions, both of which are being considered to
      replace the ASTRO definition by the 2005 meeting of the Radiation Therapy
      Oncology Group-ASTRO consensus panel.

PMID- 16406392
TI  - Initial dosimetric experience using simple three-dimensional conformal external
      beam accelerated partial-breast irradiation.
AB  - PURPOSE: Several accelerated partial-breast irradiation (APBI) techniques are
      being investigated in patients with early-stage breast cancer. We present our
      initial experience using three-dimensional conformal radiation therapy (3D-CRT).
      METHODS AND MATERIALS: Sixty-one patients with tumors of 2 cm or less and
      negative axillary nodes were treated with 3D-CRT accelerated partial-breast
      irradiation (APBI) between August 2003 and March 2005. The prescribed radiation
      dose was 32 Gy in 4-Gy fractions given twice daily. Efforts were made to minimize
      the number of beams required to achieve adequate planning target volume (PTV)
      coverage. RESULTS: A combination of photons and electrons was used in 85% of
      patients. A three-field technique that consisted of opposed, conformal tangential
      photons and enface electrons was employed in 43 patients (70%). Nine patients
      (15%) were treated with a four-field arrangement, which consisted of three photon
      fields and enface electrons. Mean PTV volumes that received 100%, 95%, and 90% of
      the prescribed dose were 93% +/- 7%, 97% +/- 4%, and 98% +/- 2%, respectively.
      Dose inhomogeneity exceeded 10% in only 7 patients (11%). Mean doses to the
      ipsilateral lung and heart were 1.8 Gy and 0.8 Gy, respectively. CONCLUSIONS:
      Simple 3D-CRT techniques of APBI can achieve appropriate PTV coverage while
      offering significant normal-tissue sparing. Therefore, this noninvasive approach
      may increase the availability of APBI to patients with early-stage breast cancer.

PMID- 16406393
TI  - Prognostic factors for disease-free survival in patients with T3-4 or N+ rectal
      cancer treated with preoperative chemoradiation therapy, surgery, and
      intraoperative irradiation.
AB  - PURPOSE: Fluoropyrimidine-radiosensitizing agents in conjunction with
      preoperative radiotherapy have proven to induce tumor and nodal downstaging
      effects, sphincter preservation promotion, and mid-term favorable survival rates.
      Intraoperative electron beam radiation therapy may improve pelvic control in
      patients with locally advanced rectal cancer stages. Potential predictive factors
      for response and disease-free survival, with intense local multidisciplinary
      approach, are analyzed. METHODS AND MATERIALS: One hundred fifteen patients with
      rectal cancer were treated with oral 5-fluorouracil or Tegafur with preoperative
      radiotherapy, surgery, and intraoperative electron beam radiation therapy to
      identify potential pre- and on-treatment characteristics that might be of
      prognostic value for disease outcome. Univariate and multivariate analyses were
      performed. RESULTS: Older patients and those treated with Tegafur were more
      likely to achieve a major histologic response, categorized as persistence of
      minimal residual microscopic disease foci in the surgical specimen ("mic"
      response). Factors unfavorably associated with disease-free survival in the
      multivariate model were male gender and persistence of macroscopic disease in the
      rectal wall ("mac" response). Accordingly, 3-year disease-free survival rates in
      the groups of patients with 0, 1, or 2 of these risk factors were 100%, 81%, and
      53%, respectively (p < 0.001). CONCLUSIONS: Females with an intense pathologic
      response (pT(mic) residue) to preoperative chemoradiotherapy have an excellent 3
      year disease-free survival. This information might be of interest for
      stratification of patients in the development of adjuvant treatment trials.

PMID- 16406394
TI  - Impact of radiotherapy for pediatric CNS atypical teratoid/rhabdoid tumor (single
      institute experience).
AB  - PURPOSE: To assess outcomes and prognostic factors in radiotherapy of pediatric
      central nervous system atypical teratoid/rhabdoid tumor (AT/RT). METHODS AND
      MATERIALS: Seventeen patients with central nervous system AT/RT were
      retrospectively reviewed after curative radiotherapy as primary or adjuvant
      therapy between January 1990 and December 2003. Overall and failure-free survival
      rates were calculated using the Kaplan-Meier method. The log-rank method was used
      to compare the effects of dosage (>50 Gy or < or =50 Gy) and treatment duration
      (>45 days or < or =45 days). Multivariate analysis was performed for prognostic
      factors. RESULTS: Median overall survival and failure-free survival were 17 and
      11 months, respectively. The 3 longest-surviving patients were older, underwent
      gross tumor removal, and completed both craniospinal and focal boost irradiation.
      Multivariate analysis revealed a significant relationship between the following:
      overall survival and performance status (p = 0.019), failure-free survival and
      total irradiation dose (p = 0.037), time interval between surgery and
      radiotherapy initiation (p = 0.031), and time interval between surgery and
      radiotherapy end point (p = 0.047). CONCLUSION: Radiotherapy is crucial in the
      treatment of AT/RT. We recommend initiating radiotherapy immediately
      postoperatively and before systemic chemotherapy in pediatric patients > or =3
      years of age.

PMID- 16406395
TI  - Anatomy-based inverse optimization in high-dose-rate brachytherapy combined with
      hypofractionated external beam radiotherapy for localized prostate cancer:
      comparison of incidence of acute genitourinary toxicity between anatomy-based
      inverse optimization and geometric optimization.
AB  - PURPOSE: To evaluate the advantages of anatomy-based inverse optimization (IO) in
      planning high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A total of
      114 patients who received HDR brachytherapy (9 Gy in two fractions) combined with
      hypofractionated external beam radiotherapy (EBRT) were analyzed. The dose
      distributions of HDR brachytherapy were optimized using geometric optimization
      (GO) in 70 patients and by anatomy-based IO in the remaining 44 patients. The
      correlation between the dose-volume histogram parameters, including the urethral
      dose and the incidence of acute genitourinary (GU) toxicity, was evaluated.
      RESULTS: The averaged values of the percentage of volume receiving 80-150% of the
      prescribed minimal peripheral dose (V(80)-V(150)) of the urethra generated by
      anatomy-based IO were significantly lower than the corresponding values generated
      by GO. Similarly, the averaged values of the minimal dose received by 5-50% of
      the target volume (D(5)-D(50)) obtained using anatomy-based IO were significantly
      lower than those obtained using GO. Regarding acute toxicity, Grade 2 or worse
      acute GU toxicity developed in 23% of all patients, but was significantly lower
      in patients for whom anatomy-based IO (16%) was used than in those for whom GO
      was used (37%), consistent with the reduced urethral dose (p <0.01). CONCLUSION:
      The results of this study suggest that anatomy-based IO is superior to GO for
      dose optimization in HDR brachytherapy for prostate cancer.

PMID- 16406397
TI  - Effect of advancing births on testosterone until 2.5 years of age and puberty in
      Iberian red deer (Cervus elaphus hispanicus).
AB  - This study aimed to determine the age of attainment of puberty, as well as the
      pattern of reproductive seasonality in males of Iberian red deer and the
      relationship of these factors with antler development. A second aim was to
      examine the effect of the advance of births on the variables mentioned. Fourteen
      males of Iberian deer were used, five of them born 2.5 months before the others
      (early group). Male deer were blood sampled from birth until 2.5 years of age to
      assess the time course of plasma testosterone. The study also included
      measurements of testicular and neck circumference. As in most cervids,
      concentration of plasma testosterone was associated to the phases of antler
      development. Early development affected testosterone titres, since the most
      precocious males in antler growth also showed higher levels of testosterone
      during the first and second year of age. In the same way, results suggested that
      the advance of calving may result in puberty attainment in the first autumn of
      its life. However, this would require an advance of calving greater than the one
      we induced since puberty in the Iberian deer is usually attained during second
      autumn of life at 15-16 months of age. Finally, calving advance also affected
      antler development. Thus, two of the five males whose birth was advanced, showed
      two antler cycles in their first year of life.

PMID- 16406396
TI  - Radiation therapy for T2N0 laryngeal cancer: A retrospective analysis for the
      impact of concurrent chemotherapy on local control.
AB  - PURPOSE: The impact of concurrent chemotherapy on the local control in patients
      with T2N0 laryngeal cancer who receive radiation therapy (RT) was evaluated.
      METHODS AND MATERIALS: Sixty-three patients with T2N0 laryngeal cancer who were
      treated by definitive RT were analyzed. The primary site of the cancer was the
      glottis in 50 patients, the supraglottis in 9 patients, and the subglottis in 4
      patients. Thirty-six patients were treated by RT alone and the remaining 27
      patients received concurrent chemoradiotherapy (CRT). RESULTS: Complete response
      (CR) was obtained in 92% of the patients who received RT alone and 100% of the
      patients who received CRT. Voice preservation in the group who received CRT (89%)
      was significantly higher than that in the group treated by RT alone (61%). The 5
      year disease-free survival rates in those who received concurrent CRT was
      significantly superior to that in the patients who received RT alone, although no
      significant difference was seen in the cause-specific survival rate between the 2
      groups. The multivariate analysis revealed that the treatment method (RT alone
      vs. CRT) was the most significant risk factor that predicted recurrence after RT.
      CONCLUSION: Concurrent CRT had a positive impact on the local control of T2N0
      laryngeal cancer.

PMID- 16406398
TI  - Comparison of effects of octopamine and insecticidal essential oils on activity
      in the nerve cord, foregut, and dorsal unpaired median neurons of cockroaches.
AB  - Essential oil constituents were tested for their neurophysiological effects in
      Periplaneta americana and Blaberus discoidalis. Eugenol depressed spontaneous and
      stimulus-evoked impulses recorded extracellularly in the abdominal nerve cord,
      with an almost complete block of spikes at 2 x 10(-3) M. Geraniol and citral had
      similar depressive effects but increased spontaneous firing at lower doses
      (threshold 2.5 x 10(-4) M). Similar effects occurred in dorsal unpaired median
      (DUM) neurons, recorded intracellularly in the isolated terminal abdominal
      ganglion of P. americana. Spontaneous firing was progressively reduced by
      increasing concentrations of eugenol, whereas geraniol and citral produced
      biphasic effects (excitation at 10(-4) M, depression at 2 x 10(-3) M). All three
      oils decreased excitability of silent DUM neurons that were depolarised by
      applied current, but eugenol (at 10(-3) M) also changed the firing pattern from
      single spikes to bursts driven by plateau potentials. All oils reduced spike
      undershoot. Low doses of citral and geraniol (threshold ca. 10(-4) M) reversibly
      increased the frequency of spontaneous foregut contractions and abolished them at
      2 x 10(-3) M (together with response to electrical stimulation). Eugenol
      reversibly reduced spontaneous activity at 10(-4) M and above. Eugenol has been
      reported to exert its insecticidal properties via a low-dose activation of
      octopamine receptors. In our studies, however, octopamine was found to have
      opposing effects to eugenol on DUM neurons and foregut activity (excitatory in
      both). Furthermore, eugenol did not affect the response to octopamine in DUM
      neurons. These results suggest that reported effects of eugenol were on a
      different sub-type of octopamine receptor.

PMID- 16406399
TI  - Pharmacokinetics of progesterone and its metabolites allopregnanolone and
      pregnanolone after oral administration of low-dose progesterone.
AB  - OBJECTIVES: To investigate the pharmacokinetics of progesterone, allopregnanolone
      and pregnanolone after treatment with a low oral dose of progesterone. METHODS:
      Eight postmenopausal women were given a single oral dose of 20 mg of micronised
      progesterone on Day 1 and 20 mg twice daily on Days 2-7. Blood samples for the
      analysis of progesterone, allopregnanolone and pregnanolone were collected, and
      pharmacokinetic parameters were calculated. RESULTS: After ingestion of a single
      dose, areas under the plasma concentration-time curve (AUC) from 0 to 12 h for
      progesterone, allopregnanolone and pregnanolone were 127%, 196% and 119% higher
      than the corresponding AUCs estimated to be caused by endogenous production. The
      maximum plasma concentration (Cmax) and the AUC values were significantly lower
      for pregnanolone than for progesterone and allopregnanolone. The trough
      concentrations at steady state (Css) were significantly higher than the baseline
      values, and Css for pregnanolone was significantly lower than for
      allopregnanolone and progesterone. Css for allopregnanolone was in the range of
      what is normally seen in the menstrual cycle. CONCLUSIONS: After ingestion of a
      low-dose of progesterone, the concentrations of allopregnanolone were in the same
      range as those of progesterone. Oral doses of 20 mg of progesterone twice daily
      to postmenopausal women produced allopregnanolone concentrations comparable to
      those achieved physiologically in premenopausal women. Low-dose oral progesterone
      may be used as a prodrug to allopregnanolone when the aim is to investigate low
      dose allopregnanolone effects in humans.

PMID- 16406400
TI  - The perception of empty and filled time intervals by rats.
AB  - In experiment 1, rats were trained in a within-subjects design to discriminate
      durations of a filled interval, and durations of an empty interval (an unfilled
      interval marked at the beginning and end by a 500 ms tone). Training and
      psychophysical testing was conducted with three sets of anchor durations. Rats
      made more long responses for filled than for empty intervals at signal durations
      greater than the geometric mean. In experiment 2, group same was trained
      similarly to the rats in experiment 1 with the ambient conditions (houselight
      illumination) remaining the same during the inter-trial interval and the empty
      intervals. Group different was trained with the houselight turned off during
      empty and filled intervals. The similarity of ambient conditions during the inter
      trial interval and the empty intervals did not significantly affect timing.
      Filled intervals were timed more precisely and they were perceived as longer than
      empty intervals of the same duration. The psychophysical functions superimposed
      across anchor duration sets. These results are the first clear evidence of a
      filled interval illusion in rats, and they suggest that this difference may
      reflect a clock rate effect (greater for filled intervals) rather than a switch
      latency effect (slower for empty intervals).

PMID- 16406401
TI  - RGD-containing molecules induce macropinocytosis in ascidian hyaline amoebocytes.
AB  - Phagocytes of the compound ascidian Botryllus schlosseri are capable of
      constitutive macropinocytosis (MP) at sites of membrane ruffling along the
      leading edge. This gives rise to the formation of initially irregular vesicles
      which then move to the inside of the cells and acquire a more regular morphology.
      Both phagocyte spreading and MP are enhanced by the recognition of molecules
      containing the sequence Arg-Gly-Asp (RGD): this suggests that, as in mammals,
      integrin activation is involved in the induction of both cell spreading and
      endocytosis. The occurrence of MP is associated with increased oxygen consumption
      and a rise in the production of superoxide anion, as indicated by nitroblue
      tetrazolium reduction, and ATP, as indicated by increased cytochrome oxidase
      activity. On the whole, our results indicate the conservation of common
      mechanisms of MP induction throughout the Chordate phylum.

PMID- 16406402
TI  - Encapsulation of amphotericin B in poly(ethylene glycol)-block-poly(epsilon
      caprolactone-co-trimethylenecarbonate) polymeric micelles.
AB  - The aim of this work was to evaluate the potential of self-assembling
      poly(ethyleneglycol)(750)-block-poly(epsilon-caprolactone-co
      trimethylenecarbonate)(4500) 50/50 copolymers (PEG-p(CL-co-TMC)) to solubilize
      amphotericin B in polymeric micelles and to disaggregate the drug to the less
      toxic monomeric form. Amphotericin B was encapsulated in the micelles upon
      dilution of a mixture of the liquid polymer and the drug in water. Its solubility
      was increased by two orders of magnitude depending on polymer concentration. The
      aggregation state of amphotericin B was decreased by PEG-p(CL-co-TMC). The
      preparation method and the loading of the polymeric micelles influenced it. The
      antifungal activity of the drug was reduced by encapsulation in the polymeric
      micelles whereas the onset of amphotericin B-induced hemolysis was delayed. PEG
      p(CL-co-TMC) micelles could be an easy method for amphotericin B encapsulation.

PMID- 16406403
TI  - An investigation into the characteristics and drug release properties of multiple
      W/O/W emulsion systems containing low concentration of lipophilic polymeric
      emulsifier.
AB  - Multiple W/O/W emulsions with high content of inner phase (Phi1=Phi2=0.8) were
      prepared using relatively low concentrations of lipophilic polymeric primary
      emulsifier, PEG 30-dipolyhydroxystearate, and diclofenac diethylamine (DDA) as a
      model drug. The investigated formulations were characterized and their stability
      over the time was evaluated by dynamic and oscillatory rheological measurements,
      microscopic analysis and in vitro drug release study. In vitro release profiles
      of the selected model drug were evaluated in terms of the effective diffusion
      coefficients and flux of the released drug. The multiple emulsion samples
      exhibited good stability during the ageing time. Concentration of the lipophilic
      primary emulsifier markedly affected rheological behaviour as well as the droplet
      size and in vitro drug release kinetics of the investigated systems. The multiple
      emulsion systems with highest concentration (2.4%, w/w) of the primary emulsifier
      had the lowest droplet size and the highest apparent viscosity and highest
      elastic characteristics. Drug release data indicated predominately diffusional
      drug release mechanism with sustained and prolonged drug release accomplished
      with 2.4% (w/w) of lipophilic emulsifier employed.

PMID- 16406404
TI  - Nanodecoy system: a novel approach to design hepatitis B vaccine for
      immunopotentiation.
AB  - The progress toward subunit vaccines has been limited by their poor
      immunogenicity and limited stability. To enhance the immune response, subunit
      vaccines universally require improved adjuvants and delivery vehicles. In the
      present study, we propose the use of ceramic core based nanodecoy systems for
      effective immunization, which seems to exhibit a broad range of surface
      properties. Nanodecoy systems were prepared by self-assembling of hydroxyapatite
      core and cellobiose and finally the hepatitis B surface antigen (HBsAg) was
      adsorbed over the preformed nanodecoy systems. HBsAg loaded nanodecoy systems
      were characterized for size, shape and antigen loading efficiency. The effect of
      processing steps on the stability and integrity of HBsAg was assessed by in vitro
      antigenicity and SDS-PAGE experiments. Nanodecoy preparations were nanometric in
      size range and almost spherical in shape. SDS-PAGE studies confirmed the
      integrity of HBsAg protein in the formulation. Vaccine efficacy was determined in
      female Balb/c mice and results indicated that specific anti-HBsAg antibody titers
      in mice receiving nanodecoy system were more efficient than the conventional
      adjuvant alum followed by subcutaneous immunization. Studies also indicated that
      nanodecoy formulations could elicit combined Th1 and Th2 immune response. It is
      inferred that nanodecoy systems are a class of novel carriers and hold potential
      as an alternative adjuvant in vaccine technology.

PMID- 16406405
TI  - Schistosoma mansoni (Platyhelminthes, Trematoda) nuclear receptors: sixteen new
      members and a novel subfamily.
AB  - Nuclear receptors (NRs) are important transcriptional modulators in metazoans.
      Sixteen new NRs were identified in the Platyhelminth trematode, Schistosoma
      mansoni. Three were found to possess novel tandem DNA-binding domains that
      identify a new subfamily of NR. Two NRs are homologues of the thyroid hormone
      receptor that previously were thought to be restricted to chordates. This study
      brings the total number of identified NR in S. mansoni to 21. Phylogenetic and
      comparative genomic analyses demonstrate that S. mansoni NRs share an
      evolutionary lineage with that of arthropods and vertebrates. Phylogenic analysis
      shows that more than half of the S. mansoni nuclear receptors evolved from a
      second gene duplication. As the second gene duplication of NRs was thought to be
      specific to vertebrates, our data challenge the current theory of NR evolution.

PMID- 16406406
TI  - Structural dynamics of the actin-myosin interface by site-directed spectroscopy.
AB  - We have used site-directed spin and fluorescence labeling to test molecular
      models of the actin-myosin interface. Force is generated when the actin-myosin
      complex undergoes a transition from a disordered weak-binding state to an ordered
      strong-binding state. Actomyosin interface models, in which residues are
      classified as contributing to either weak or strong binding, have been derived by
      fitting individual crystallographic structures of actin and myosin into
      actomyosin cryo-EM maps. Our goal is to test these models using site-directed
      spectroscopic probes on actin and myosin. Starting with Cys-lite constructs of
      both yeast actin (ActC) and the Dictyostelium myosin II motor domain (S1dC), site
      directed labeling (SDL) mutants were generated by mutating residues to Cys in the
      proposed weak and strong-binding interfaces. This report focuses on the effects
      of forming the strong-binding complex on four SDL mutants, two located in the
      proposed weak-binding interface (ActC5 and S1dC619) and two located in the
      proposed strong-binding interface (ActC345 and S1dC401). Neither the mutations
      nor labeling prevented strong actomyosin binding or actin-activation of myosin
      ATPase. Formation of the strong-binding complex resulted in decreased spin and
      fluorescence probe mobility at all sites, but both myosin-bound probes showed
      remarkably high mobility even after complex formation. Complex formation
      decreased solvent accessibility for both actin-bound probes, but increased it for
      the myosin-bound probes. These results are not consistent with a simple model in
      which there are discrete weak and strong interfaces, with only the strong
      interface forming under strong-binding conditions, nor are they consistent with a
      model in which surface residues become rigid and inaccessible upon complex
      formation. We conclude that all four of these residues are involved in the strong
      actin-myosin interface, but this interface is remarkably dynamic, especially on
      the surface of myosin.

PMID- 16406407
TI  - During the early phase of HIV-1 DNA synthesis, nucleocapsid protein directs
      hybridization of the TAR complementary sequences via the ends of their double
      stranded stem.
AB  - Reverse transcription of HIV-1 genomic RNA requires two obligatory strand
      transfers. During the first strand transfer reaction, the minus strand strong
      stop DNA (ss-cDNA) is transferred by hybridization of complementary sequences
      located at the 3' ends of the ss-cDNA and genomic template, respectively. In HIV
      1, the major components of ss-cDNA transfer are the terminally redundant
      structured TAR elements and the nucleocapsid protein NCp7, which actively
      chaperones the hybridization of cTAR DNA to TAR. In the present study, we
      investigated the annealing kinetics of TAR with fluorescently labelled cTAR
      derivatives both in the absence and in the presence of NC(12-55), a peptide that
      contains the finger and C-terminal domains of NCp7. The annealing of TAR with
      cTAR involves two second-order kinetic components that are activated by at least
      two orders of magnitude by NC(12-55). The NC-promoted activation of cTAR-TAR
      annealing was correlated with its ability to destabilize the lower half of TAR
      stem, in order to generate the single-stranded complementary regions for
      nucleating the duplex structures. The two kinetics components have been assigned
      to two different pathways. The rapid one does not lead to extended duplex
      formation but is associated with a limited annealing of the terminal bases of
      cTAR to TAR. On the other hand, extended duplex formation follows a slower
      pathway that is limited kinetically by the nucleation of residues located mainly
      within the central double-stranded segment of both cTAR and TAR stems. An
      alternative mechanism involving an interaction through TAR and cTAR loops has
      been observed but is a minor pathway in the present conditions.

PMID- 16406408
TI  - The transition state for folding of a peripheral subunit-binding domain contains
      robust and ionic-strength dependent characteristics.
AB  - The denaturant dependencies of the folding and unfolding kinetics were used to
      characterize the structure of the transition state for folding of E3BD, a
      peripheral subunit-binding domain. For the majority of E3BD mutants, the Phi
      values calculated at 298 K from the analysis of chevron plots were in good
      agreement with those previously determined at 325 K using Arrhenius analysis.
      This agreement further demonstrates the general robustness of Phi-value analyses,
      since different experiments, methods of denaturation and thermodynamic
      assumptions were used to determine each set of Phi(F) values. The structure of
      the transition state for folding was grossly conserved at 298 K and 325 K, with
      residues in Helix I playing a lesser role in folding than those located in the
      3(10) helix, disordered loop and Helix II. However, the energetic contributions
      of a cluster of basic residues close to the N-terminus and Helix I, which are an
      integral part of the ligand-binding site, were susceptible to ionic strength
      effects because of electrostatic strain in native and transition states of E3BD
      at low ionic strength. We found no evidence of the downhill folding previously
      proposed for E3BD, even though the conditions employed in this study
      significantly increased the energetic bias towards the native state.

PMID- 16406409
TI  - Metal bridges between the PhoQ sensor domain and the membrane regulate
      transmembrane signaling.
AB  - Bacterial histidine kinases respond to environmental stimuli by transducing a
      signal from an extracytosolic sensor domain to a cytosolic catalytic domain.
      Among them, PhoQ promotes bacterial virulence and is tightly repressed by the
      divalent cations such as calcium and magnesium. We have determined the crystal
      structure of the PhoQ sensor domain from Salmonella typhimurium in the Ca2+-bound
      state, which reveals a highly negatively charged surface that is in close
      proximity to the inner membrane. This acidic surface binds at least three Ca2+,
      which mediate the PhoQ-membrane interaction. Mutagenesis analysis indicates that
      structural integrity at the membrane proximal region of the PhoQ sensor domain
      promotes metal-mediated repression. We propose that depletion or displacement of
      divalent cations leads to charge repulsion between PhoQ and the membrane, which
      initiates transmembrane signaling through a change in orientation between the
      PhoQ sensor domain and membrane. Therefore, both PhoQ and the membrane are
      required for extracytosolic sensing and transmembrane signaling.

PMID- 16406410
TI  - Genetic variability of encephalomyocarditis virus (EMCV) isolates.
AB  - In order to evaluate the variability of encephalomyocarditis virus (EMCV), field
      isolates originating from different European regions and inducing different
      clinical pictures in pigs have been molecularly characterised. The regions
      targeted were the poly(C) tract, a part of the 5'-UTR (360 nucleotides), the
      Leader gene (201 nucleotides), the complete capsid coding region (2502
      nucleotides), the 2A gene (403 nucleotides), the end of the 3D polymerase gene
      (305 nucleotides) and the 3'-UTR (123 nucleotides). Analyses have also been
      performed on a virulent field isolate, which had been subjected to serial
      passages in vivo and in vitro resulting, in the case of the in vitro passaged
      virus, in attenuation, as demonstrated by animal experiments. The present study
      shows that different clinical pictures, such as acute fatal myocarditis or
      reproductive failure, may not only be caused by EMCV isolates which are
      genetically diverse but also by the same isolate. Thus no correlation could be
      demonstrated between genotype and clinical disease. However, the European isolate
      which showed the highest genetic divergence also gave rise to a more complex
      clinical picture. Despite EMCV having been isolated from cases of acute fatal
      myocarditis in pigs in certain areas of the world for many years, clinical
      disease, including a variety of clinical pictures and pathogenicity, has only
      been recognised in Europe since 1986 and thus it can be considered an emerging
      disease in this region. These findings, associated with the reported phenotype
      changes of the virus under environmental changes (passages), along with its wide
      distribution among vertebrate species (including higher primates), shows the
      validity of considering EMCV as a potential pathogen for recipients in
      xenotransplantation.

PMID- 16406411
TI  - Antidiabetic effects of dietary administration of Aloe arborescens Miller
      components on multiple low-dose streptozotocin-induced diabetes in mice:
      investigation on hypoglycemic action and systemic absorption dynamics of aloe
      components.
AB  - We carried out three experimental trials to determine antidiabetic effects of
      Aloe arborescens Miller components. Firstly, ICR mice which received frequent
      injections of streptozotocin (Sz) in small doses (low-dose Sz-induced diabetes
      mice) were fed ad libitum with basal diets supplemented with components of Aloe
      arborescens Miller var. natalensis Berger (Kidachi aloe) and Aloe vera Linne from
      31 days before to 73 days after the Sz injections. Variation in blood glucose
      levels, incidence rates of insulitis and blood insulin levels were examined
      during the trial. As a result, groups receiving diets supplemented at the rate of
      2% with whole leaf of Kidachi aloe and 10 KDa fraction powder (a fraction with
      less than 10 KDa molecular weight derived from Kidachi aloe leaf skin juice by
      ultra filtration) significantly suppressed the elevation of blood sugar as
      compared to a control group receiving basal diet. In contrast, there was no
      significant effect with Aloe vera leaf pulp powder. Insulitis emerged at the rate
      of 87% in the basal diet group. On the contrary, the whole aloe leaf and 10 KDa
      fraction groups significantly decreased the incidence of insulitis and incidence
      rates of whole aloe leaf and 10 KDa fraction powder were 51 and 38%,
      respectively. While insulin levels in the basal diet group averaged at 0.05 ng,
      more than four times the insulin level was observed in the 10 KDa group relative
      to the basal diet group. Secondary, the inhibitory effects of test materials on
      intestinal glucose absorption were observed using the jejunum of rats. A strong
      inhibitory action on intestinal glucose absorption was observed in the 10 KDa
      fraction powder group. Thirdly, phenol compounds derived from aloe in the blood
      serum and organs were quantitatively measured by a HPLC following forced
      administration of aloe components to rats to determine absorption kinetics of
      aloe components inside the body. The primary component of aloe phenol compounds
      is the same component of the 10 KDa fraction powder and it was found in the
      pancreas and liver in addition to in the blood serum. The above results indicate
      that fore and aft when Sz injections could cause selective toxicity to B cells of
      islets, the dietary administration of 10 KDa fraction powder to mice would lead
      to the persistence of aloe phenol compound having an antioxidant activity in the
      pancreas and blood, which could protect islets of Langerhans from the destruction
      caused by methyl radical derived from Sz. The results also suggested the
      possibility of the 10 KDa fraction powder to alleviate the burden of insulin
      secretion as it has an inhibitory action on glucose absorption in the jejunum of
      rats.

PMID- 16406412
TI  - Affinity of Iresine herbstii and Brugmansia arborea extracts on different
      cerebral receptors.
AB  - Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim
      (Solanaceae) are used in the northern Peruvian Andes for magic-therapeutical
      purposes. The traditional healers use Iresine herbstii with the ritual aim to
      expel bad spirits from the body. Furthermore, Iresine herbstii was used in
      association with other plants, such as Trichocereus pachanoi Britt. et Rose, for
      divination, to diagnose diseases, and to take possession of another identity.
      Also, species of Brugmansia have been reported to be used during ritual practices
      for magical and curative purposes. Given the above evidence, the aim of the
      present study is to evaluate if the central effects of Iresine herbstii and
      Brugmansia arborea could be associated with interaction with SNC receptors. Two
      Iresine herbstii extracts (methanolic and aqueous) and one Brugmansia arborea
      aqueous extract were tested for in vitro affinity on 5-HT(1A), 5-HT(2A), 5
      HT(2C), D1, D2, alpha(1), and alpha(2) receptors by radioligand binding assays.
      The biological materials for binding assay (cerebral cortex) were taken from male
      Sprague-Dawley rats. The extracts affinity for receptors is definite as
      inhibition percentage of radioligand/receptor binding and measured as the
      radioactivity of remaining complex radioligand/receptor. The data obtained for
      Iresine extracts have shown a low affinity for the 5-HT(1A) receptor and no
      affinity for 5-HT(2A) receptor. Otherwise the methanolic extract showed affinity
      for 5-HT(2C) receptor (IC(50): 34.78 microg/ml) and for D1 receptor (IC(50):
      19.63 microg/ml), instead the Iresine aqueous extract displayed a lower affinity
      for D1 (48.3% at the maximum concentration tested) and a higher value of affinity
      for D2 receptors (IC(50): 32.08 microg/ml). The Brugmansia aqueous extract
      displayed affinity for D1 receptors (IC(50): 17.68 microg/ml), D2 receptors
      (IC(50): 15.95 microg/ml) and weak affinity for the serotoninergic receptors.
      None of the three extracts showed relevant affinity to the alpha(1), and alpha(2)
      receptors. The results of our experiments indicate that Iresine herbstii
      methanolic extract was able to interact with the central 5-HT(2C) and D1
      receptors and Iresine herbstii aqueous extract showed affinity for D2 receptors,
      thus confirming their ritual use. Instead Brugmansia arborea was able to interact
      only with the central dopamine receptors tested. Parallel studies are currently
      in progress for evaluating the extracts affinity and active components towards
      these and other receptor types (GABAergic).

PMID- 16406413
TI  - Lipid lowering activity of Eclipta prostrata in experimental hyperlipidemia.
AB  - The plant Eclipta prostrata is used in the traditional medical practices of India
      to treat hepatic diseases and hyperlipidemia. The total alcoholic extract of the
      plant when tested for antihyperlipidemic potential, exhibited a dose-dependent
      activity in albino rats when compared to standard drugs. The activity was
      assessed by studying the lipid profiles of serum, liver and heart of the control
      and drug-treated animals. The results lend support to the traditional use of
      Eclipta prostrata in the treatment of hyperlipidemia.

PMID- 16406414
TI  - Anti-HIV-1 protease- and HIV-1 integrase activities of Thai medicinal plants
      known as Hua-Khao-Yen.
AB  - Ethanolic- and water extracts from five species of Thai medicinal plants known as
      Hua-Khao-Yen were tested for their inhibitory effects against HIV-1 protease (HIV
      PR) and HIV-1 integrase (HIV-1 IN). The result revealed that the ethanolic (EtOH)
      extract of Smilax corbularia exhibited anti-HIV-1 IN activity with an IC50 value
      of 1.9 microg/ml, followed by the water extract of Dioscorea birmanica (IC50 =
      4.5 microg/ml), the EtOH extract of Dioscorea birmanica (IC50 = 4.7 microg/ml),
      the water extract of Smilax corbularia (IC50 = 5.4 microg/ml), the EtOH extract
      of Smilax glabra (IC50 = 6.7 microg/ml) and the water extract of Smilax glabra
      (IC50 = 8.5 microg/ml). The extracts of Pygmaeopremna herbacea and Dioscorea
      membranacea were apparently inactive (IC50 > 100 microg/ml). Interestingly, only
      the EtOH extract of Dioscorea membranacea showed appreciable activity (IC50 = 48
      microg/ml) against HIV-1 PR, while the other extracts possessed mild activity.
      This result strongly supported the basis for the use of Smilax corbularia and
      Dioscorea membranacea for AIDS treatment by Thai traditional doctors.

PMID- 16406415
TI  - Anti-ulcerogenic and anti-inflammatory activity of the methanolic extract of
      Larrea divaricata Cav. in rat.
AB  - Larrea divaricata Cav. (Zygophyllaceae) is used in popular medicine as anti
      inflammatory and anti-rheumatic drug, containing higher amounts of
      nordihydroguaiaretic acid, a well-known free radical scavenger. Here we describe
      the gastric anti-ulcerogenic effect of the methanolic extract of Larrea
      divaricata (LdME) leaves in rat, using absolute ethanol and HCl 0.6N as
      necrotizing agents, and the effect of blocking endogenous sulfhydryl (SH) groups
      with N-ethylmaleimide (NEM). We also studied the anti-inflammatory activity of
      LdME in two rat experimental models: cotton pellet induced granuloma and
      arthritis induced by adjuvant-carrageenan. Influence of treatment in body weight
      and some lymphoid organs was evaluated. Finally, the free radical scavenging
      capacity of LdME was determined by the method of 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) inhibition. LdME demonstrated anti-ulcerogenic effect in rats, and it was
      shown that the endogenous SH compounds were not involved in the mechanism of
      action. LdME also showed inhibitory activity in the applied models of
      inflammation, being more effective in the acute phase. No effect was observed
      concerning the weight of spleen, thymus and body. The extract proved to possess
      elevated free radical scavenging capacity which may contribute to the observed
      gastric anti-ulcerogenic and anti-inflammatory activity.

PMID- 16406416
TI  - Effects of Scutellariae Radix on gene expression in HEK 293 cells using cDNA
      microarray.
AB  - The aim of the present study was to elucidate the molecular mechanisms underlying
      the anti-inflammatory effect of Scutellaria Radix (SR). The complementary DNA
      (cDNA) microarray method was used to survey the effects of SR on the changes of
      gene expression profile in HEK293 cells. Based on differential expression, 66
      genes were selected for further analysis from 9,600 candidate genes in the
      microarray; 23 genes were validated by RT-PCR. The broad spectrum of the
      differentially expressed genes, including those associated with inflammation,
      immune response, energy metabolism, as well as others, such as ISGF3G, IL6ST,
      CD98, ATP5G2, PHKG2, YB-1 and SLC7A4, indicate overall cellular response to SR
      treatment. Our results suggest that the anti-inflammatory effect of SR may be
      related to IL6ST down-expression, and over-expression of CD98. Moreover, SR
      related improvement in immune response may be related to the ISGF3G over
      expression.

PMID- 16406417
TI  - Impact of Andrographis paniculata crude extract on mouse hepatic cytochrome P450
      enzymes.
AB  - Modulatory influence of Andrographis paniculata crude extract on cytochrome P450
      (CYP) enzymes was performed by administration of the crude extract of
      Andrographis paniculata to ICR male mice. Total hepatic P450 content was not
      significantly modified by either the aqueous or the alcoholic extracts of
      Andrographis paniculata. Assessment of hepatic microsomal P450 activities by
      alkoxyresorufin O-dealkylations noted that both the aqueous and alcoholic
      extracts of Andrographis paniculata significantly increased ethoxyresorufin O
      dealkylase and pentoxyresorufin O-dealkylase activities, while those of
      methoxyresorufin O-dealkylase activities were not elevated. These results
      suggested that Andrographis paniculata might effectuate hepatic cytochrome P450
      enzymes of which CYP1A1 and CYP2B are the responsive P450 isoforms.

PMID- 16406418
TI  - Anti-quorum sensing activity of medicinal plants in southern Florida.
AB  - Bacterial intercellular communication, or quorum sensing (QS), controls the
      pathogenesis of many medically important organisms. Anti-QS compounds are known
      to exist in marine algae and have the ability to attenuate bacterial
      pathogenicity. We hypothesized that terrestrial plants traditionally used as
      medicines may also produce anti-QS compounds. To test this hypothesis, 50
      medicinal plants from southern Florida were screened for anti-QS activity using
      two biomonitor strains, Chromobacterium violaceum and Agrobacterium tumefaciens.
      Of these plants, six showed QS inhibition: Conocarpus erectus L. (Combretaceae),
      Chamaecyce hypericifolia (L.) Millsp. (Euphorbiaceae), Callistemon viminalis
      (Sol. ex Gaertn.) G. Don (Myrtaceae), Bucida burceras L. (Combretaceae),
      Tetrazygia bicolor (Mill.) Cogn. (Melastomataceae), and Quercus virginiana Mill.
      (Fagaceae). This study introduces not only a new mode of action and possible
      validation for traditional plant use, but also a potentially new therapeutic
      direction for the treatment of bacterial infections.

PMID- 16406419
TI  - Effect of curcumin on the expression of LDL receptor in mouse macrophages.
AB  - To investigate the molecular mechanisms of lipid-lowering drug, Rhizoma Curcumae
      Longae, we treated the mouse macrophages with curcumin, which was purified from
      the ethanol extraction of Rhizoma Curcumae Longae. The LDL receptors expressed in
      the macrophages were determined by ELISA, FLISA and assay of LDL uptake. Here for
      the first time, we found that curcumin obviously up-regulated the expression of
      LDL receptor in mouse macrophages, and the dose-effect relationship was
      demonstrated.

PMID- 16406420
TI  - 3-Hydroxybenzo[a]pyrene in the urine of smokers and non-smokers.
AB  - The people studied were male volunteers without occupational and dietary exposure
      to PAH: 27 smokers (10 cigarettes or more) and 27 non-smokers matched for age and
      socio-professional category. For each person, all the 24h voided urine samples
      were reassembled in a single sample. 1-Hydroxypyrene (1-OHPy) and 3
      hydroxybenzo[a]pyrene (3-OHBaP) were then determined by automated column
      switching high-performance liquid chromatography. Urinary 1-OHPy ranged from
      0.041 to 0.530 micromol/molCreatinine (arithmetic mean 0.144, median 0.115) for
      smokers and from 0.01 to 0.148 mmol/molCreatinine (arithmetic mean 0.044, median
      0.032) for non-smokers. These values are close to those of some other studies.
      Urinary 3-OHBaP ranged from <0.01 to 0.084 nmol/molCreatinine (arithmetic mean
      0.030, median 0.023) for smokers and from <0.01 to 0.045 nmol/molCreatinine
      (arithmetic mean 0.014, median 0.011) for non-smokers. Considering more
      particularly the urinary 3-OHBaP values, the influence of smoking could be
      important among workers exposed to low levels of BaP (<100 ng/m(3)) and the
      concentrations for smokers were equivalent to most of the preshift values of
      exposed workers. The dietary BaP intake was slightly lower than the BaP intake
      for an average smoker. From the present study, temporary basic reference levels
      may be proposed for urinary 3-OHBaP.

PMID- 16406421
TI  - CYP19 (TTTA)n polymorphism and breast cancer risk in Brazilian women.
AB  - A prolonged or increased exposure to endogenous estrogens associated with genetic
      factors are considered to be the main risk factors for breast cancer. The CYP19
      gene encodes the enzyme aromatase, which catalyzes the conversion of androgens
      into estrogens. CYP19 alleles containing different numbers of tetranucleotide
      TTTA repeats in intron 4 have been associated with increased breast cancer risk.
      In this study we investigated, for the first time, the frequency of CYP19 (TTTA)n
      alleles in a South American population (n = 475) and analyzed the risk for
      developing breast cancer in a case-control study comprising 135 cases and 270 age
      matched controls. It is shown that Brazilians possess not only the alleles
      identified in all the other populations studied so far (alleles containing from 7
      to 13 TTTA repeats), but also the (TTTA)6 allele, that had never been described
      before. The (TTTA)10 allele was three times more frequent in cases when compared
      to controls and presented a significant positive association (p = 0.048) with
      breast cancer development in Brazilians.

PMID- 16406423
TI  - An unusual appearance of a common pollen type indicates the scene of the crime.
AB  - Forensic palynology is a useful source of evidence in cases of violence committed
      in the open. A young girl was grabbed off the street, threatened and brutally
      raped. During the investigation the exact place of the rape became an issue.
      Growing around the scene identified by the victim were shrubs identified as
      Coprosma, a common New Zealand plant and one that produces abundant, easily wind
      dispersed pollen. Abundant Coprosma pollen was found at the scene. The pollen
      were unusual in that the site was very damp, encouraging fungal growth, and
      fungal hyphae had penetrated the pores of many of the tricolporate pollen grains.
      Some grains had fungal spores inside. Coprosma pollen identical in preservational
      characteristics and morphology to those from the scene and containing fungal
      hyphae and spores were found in considerable numbers on the victim's clothes.
      This and rare Coprosma pollen grains and fungal remains recovered from vaginal
      swabs provided evidence that she had been at the scene where she claimed to have
      been raped. The diversity of pollen types recovered from the clothing in this
      case provides further evidence of the usefulness of clothing in picking up and
      retaining pollen from crime scenes and that obvious staining on clothes is not a
      pre-requisite for good pollen recovery. It also demonstrates the importance of
      collecting samples from different parts of the same garment in order to get a
      full picture of events since different parts of a garment can come into contact
      with different plants or different parts of the ground in a scuffle. It is also
      demonstrated that significant evidential material can be collected from the body,
      in this case from vaginal swabs from the victim. Forensic palynology should be
      considered in every case of violent assault, especially, but not exclusively,
      when having occurred in an open area subject to extensive pollen settlement.

PMID- 16406422
TI  - A fatal poisoning with 5-methoxy-N,N-diisopropyltryptamine, Foxy.
AB  - A fatal overdose involving case by 5-methoxy-N,N-diisopropyltryptamine (5-MeO
      DIPT) is reported. 5-MeO-DIPT and its two metabolites, 5-hydroxy-N,N
      diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N-isopropyltryptamine (5-MeO
      NIPT), were identified by LC-MS. The level of 5-MeO-DIPT, 5-OH-DIPT and 5-MeO
      NIPT in blood and urine was 0.412, 0.327 and 0.020 microg/ml, and 1.67, 27.0 and
      0.32 microg/ml, respectively. These blood and urine levels were higher than
      published data for such poisoning.

PMID- 16406424
TI  - Mapping electrostatic potential of a protein on its hydrophobic surface:
      implications for crystallization of Cytochrome P450scc.
AB  - Calculation and combined visualization of electrostatic and hydrophobic
      properties of Cytochrome P450scc based on two very different homology models
      allowed to identify extensive hydrophobic patches with neutral electrostatic
      potential and mutations removing such patches and thus expecting to facilitate
      crystallization of Cytochrome P450scc, especially for the nanotemplate
      crystallization method. Implications are discussed for optimizing crystallization
      and other aspects of protein surface properties and protein recognition.

PMID- 16406425
TI  - A model describing the effect of sex-reversed YY fish in an established wild
      population: The use of a Trojan Y chromosome to cause extinction of an introduced
      exotic species.
AB  - A novel means of inducing extinction of an exotic fish population is proposed
      using a genetic approach to shift the ratio of male to females within a
      population. In the proposed strategy, sex-reversed fish containing two Y
      chromosomes are introduced into a normal fish population. These YY fish result in
      the production of a disproportionate number of male fish in subsequent
      generations. Mathematical modeling of the system following introduction of YY
      fish at a constant rate reveals that female fish decline in numbers over time,
      leading to eventual extinction of the population.

PMID- 16406426
TI  - Science and technology of farm animal cloning: state of the art.
AB  - Details of the first mammal born after nuclear transfer cloning were published by
      Steen Malte Willadsen in 1986. In spite of its enormous scientific significance,
      this discovery failed to trigger much public concern, possibly because the donor
      cells were derived from pre-implantation stage embryos. The major breakthrough in
      terms of public recognition has happened when Ian Wilmut et al. [Wilmut, I.,
      Schnieke, A.E., McWhir, J., Kind, A.J., Campbell, K.H., 1997. Viable offspring
      derived from fetal es adult mammalian cells. Nature 385, 810-813] described the
      successful application of almost exactly the same method, but using the nuclei of
      somatic cells from an adult mammal, to create Dolly the sheep. It has become
      theoretically possible to produce an unlimited number of genetic replicates from
      an adult animal or a post-implantation foetus. Since 1997 a number of different
      species including pigs, goats, horses, cats, etc. have been cloned with the
      somatic cell nuclear transfer technique. Although the technology still has
      relatively low success rates and there seems to be substantial problems with the
      welfare of some of the cloned animals, cloning is used both within basic research
      and the biomedical sector. The next step seems to be to implement cloning in the
      agricultural production system and several animals have been developed in this
      direction. This article reviews the current state of the art of farm animal
      cloning from a scientific and technological perspective, describes the animal
      welfare problems and critically assess different applications of farm animal
      cloning. The scope is confined to animal biotechnologies in which the use of cell
      nuclear transfer is an essential part and extends to both biomedical and
      agricultural applications of farm animal cloning. These applications include the
      production of genetically identical animals for research purposes, and also the
      creation of genetically modified animals. In the agricultural sector, cloning can
      be used as a tool within farm animal breeding. We do not intend to give an
      exhaustive review of the all the literature available; instead we pinpoint issues
      and events pivotal to the development of current farm animal cloning practices
      and their possible applications.

PMID- 16406427
TI  - Tracheostomy abolishes paradoxical activation of the vocal cord adductor in
      multiple system atrophy.
AB  - OBJECTIVES: Inspiratory activation of the vocal cord adductor, which causes
      paradoxical vocal cord motion, develops in patients with multiple system atrophy
      (MSA). To confirm the hypothesis that airway reflexes trigger such paradoxical
      activation, we investigated the effects of tracheostomy on the adductor
      activation in a MSA patient. METHODS: We compared the adductor electromyograms
      before and after breathing was diverted to a tracheostoma under propofol
      anesthesia. RESULTS: The adductor inspiratory activation disappeared during
      tracheostoma breathing. CONCLUSION: Airway reflexes as well as MSA-related damage
      to the respiratory center contribute to the generation of paradoxical adductor
      activation in MSA patients.

PMID- 16406428
TI  - Extramedullary plasmacytoma of the larynx.
AB  - Extramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm that occurs in
      the soft tissues, especially in the upper airways. We report two cases of
      laryngeal EMP, both of which were treated by surgical resection, one with and one
      without combination radiotherapy. A 39-year-old male was diagnosed with a
      laryngeal tumor localized in the left arytenoid region in October 1999. Biopsy
      showed the tumor to be a plasmacytoma. He underwent a direct laryngoscopy and
      resection of the tumor with a KTP laser. Consequently, he received radiotherapy
      to a total dose of 60 Gy. He has remained clear, with no local recurrence during
      6 years of follow-up. A 59-year-old male was diagnosed with an epiglottic tumor
      in December 1989. He underwent a direct laryngoscopy and removal of the tumor.
      Histopathological study of the tumor showed a diffuse proliferation of
      plasmacytoid cells. He has remained diseasefree during 15 years of follow-up.

PMID- 16406429
TI  - Tidal and longitudinal variation of faecal indicator bacteria in an estuarine
      creek in south-east Queensland, Australia.
AB  - A two-part study conducted in Elimbah Creek, a shallow estuarine waterway in
      south-east Queensland, Australia, examined the variations in physico-chemical
      parameters of water quality, chlorophyll a, and faecal indicator bacteria
      abundances of total coliform, Escherichia coli and enterococci, spatially at high
      and low tide and also over a 12h tidal cycle. Gradients of increasing faecal
      indicator bacteria from the mouth to the upper, tidal freshwater reaches were
      observed, despite isolated peaks during either tidal phase. Phytoplankton biomass
      (measured as chlorophyll a) did not noticeably increase during the study.
      Variations in the abundances of all three faecal indicator bacteria and their
      correlations with physico-chemical parameters indicated that although the creek
      was likely subject to some level of faecal contamination, tidal movement serves
      to limit faecal indicator and phytoplankton levels in the creek through physico
      chemical stress and dilution. However, each faecal indicator bacteria
      investigated provided different estimations of faecal contamination, which
      challenges the effectiveness of employing a single type of faecal indicator
      bacteria when investigating the level of faecal contamination in waterways.

PMID- 16406430
TI  - Hypericum pollen determines the presence of burglars at the scene of a crime: an
      example of forensic palynology.
AB  - Two male intruders entered a house in which the sole female occupant slept having
      left the back door unlocked for the return of her live-in boyfriend. She awoke
      and saw strangers in her bedroom. The intruders ran off, one leaving a jacket
      behind on the kitchen floor. One of the intruders subsequently returned to
      recover his jacket, but in his rush to leave the house he brushed against a
      flowering Hypericum bush growing just outside the back door. A suspect was
      arrested later that day and charged with indecent assault on a female and
      burglary, but denied any involvement and refused to name any associate. A day
      following the offence the suspect's clothes were taken for forensic examination.
      Pollen analysis of selected parts of his clothing showed that his track pants
      contained 14% Hypericum pollen, denim jacket 24%, and polo shirt 27.5%. Traces of
      Hypericum pollen occurred on other items. Most of these pollen grains still had
      their cell contents preserved and were on the clothing in clumps consistent with
      having recently been collected by the clothing and not having been aerially
      dispersed. The pollen from the Hypericum bush was identical in colour, shape,
      development, and size range to the pollen from the clothing. The clothes had so
      much Hypericum pollen on them that they had to have been in direct and intimate
      contact with a flowering bush. Pollen evidence is by its nature circumstantial
      and often cannot be used on its own to convict, or more strictly to determine the
      truth. The suspect may have been in contact with Hypericum elsewhere, but
      detailed investigations indicated that this was unlikely. In 30 years of New
      Zealand forensic work Hypericum had only ever been found on clothing in trace
      amounts. This is but one way in which forensic palynology can assist law
      enforcement agencies to determine the history behind a criminal action, and
      demonstrates that forensic palynology should be considered as an integral part of
      any criminal investigation.

PMID- 16406431
TI  - [Pseudomonas aeruginosa and Surfactant-associated Proteins A and D].
AB  - Surfactant-associated proteins A and D (SP-A and SP-D) are two pulmonary
      collectins that bind to bacterial, fungal and viral pathogens and have multiples
      classes of receptors on pneumocyte and macrophage membrane. They are
      chemoattractant for phagocytes, enhance uptake and killing of bacteria by
      macrophages and neutrophils. These molecules also act as activation ligand on
      macrophages and neutrophils to enhance phagocytosis, resulting in an increased
      bacterial clearance. Depending on activation of cells by stimuli, SP-A and SP-D
      modulate production of antimicrobial free radicals by phagocytes and secretion of
      cytokines. In vivo, SP-A deficient mice infected with Pseudomonas aeruginosa (P.
      aeruginosa) have decreased bacterial clearance and exacerbated inflammatory
      response in the lungs. Serious alterations in macrophages and increased
      production of reactive oxygen species were found in non-infected SP-D deficient
      mice. Patients with cystic fibrosis are frequently colonized by P. aeruginosa.
      Decreased levels of SP-A and SP-D have been measured in bronchoalveolar lavage
      fluid of these patients, as well as patients with acute pneumonia but no chronic
      lung disease. P. aeruginosa secretes various proteases, among them, elastase and
      protease IV have been found to degrade SP-A and SP-D and abrogate their immune
      function. However, further investigations are necessary to examine whether these
      deficiencies facilitate P. aeruginosa infections or stand as consequences.

PMID- 16406432
TI  - Method for detecting DNA strand breaks in mammalian cells using the Deinococcus
      radiodurans PprA protein.
AB  - In a previous study, we identified the novel protein PprA that plays a critical
      role in the radiation resistance of Deinococcus radiodurans. In this study, we
      focussed on the ability of PprA protein to recognize and bind to double-stranded
      DNA carrying strand breaks, and attempted to visualize radiation-induced DNA
      strand breaks in mammalian cultured cells by employing PprA protein using an
      immunofluorescence technique. Increased PprA protein binding to CHO-K1 nuclei
      immediately following irradiation suggests the protein is binding to DNA strand
      breaks. By altering the cell permeabilization conditions, PprA protein binding to
      CHO-K1 mitochondria, which is probably resulted from DNA strand break immediately
      following irradiation, was also detected. The method developed and detailed in
      this study will be useful in evaluating DNA damage responses in cultured cells,
      and could also be applicable to genotoxic tests in the environmental and
      pharmaceutical fields.

PMID- 16406433
TI  - 7H-Dibenzo[c,g]carbazole and 5,9-dimethyldibenzo[c,g]carbazole exert multiple
      toxic events contributing to tumor promotion in rat liver epithelial 'stem-like'
      cells.
AB  - Immature liver progenitor cells have been suggested to be an important target of
      hepatotoxins and hepatocarcinogens. The goal of the present study was to assess
      the impact of 7H-dibenzo[c,g]carbazole (DBC) and its tissue-specific carcinogenic
      N-methyl (N-MeDBC) and 5,9-dimethyl (DiMeDBC) derivatives on rat liver epithelial
      WB-F344 cells, in vitro model of liver progenitor cells. We investigated the
      cellular events associated with both tumor initiation and promotion, such as
      activation of aryl hydrocarbon receptor (AhR), changes in expression of enzymes
      involved in metabolic activation of DBC and its derivatives, effects on cell
      cycle, cell proliferation/apoptosis and inhibition of gap junctional
      intercellular communication (GJIC). N-MeDBC, a tissue-specific sarcomagen, was
      only a weak inhibitor of GJIC or inducer of AhR-mediated activity, and it did not
      affect either cell proliferation or apoptosis. DBC was efficient GJIC inhibitor,
      while DiMeDBC manifested the strongest AhR inducing activity. Accordingly,
      DiMeDBC was also the most potent inducer of cytochrome P450 1A1 (CYP1A1) and
      CYP1A2 expression among the three compounds tested. Both DBC and DiMeDBC induced
      expression of CYP1B1 and aldo-keto reductase 1C9 (AKR1C9). N-MeDBC failed to
      significantly upregulate CYP1A1/2 and it only moderately increased CYP1B1 or
      AKR1C9. Only the potent liver carcinogens, DBC and DiMeDBC, caused a significant
      increase of p53 phosphorylation at Ser15, an increased accumulation of cells in S
      phase and apoptosis at micromolar concentrations. In addition, DiMeDBC was found
      to stimulate cell proliferation of contact-inhibited WB-F344 cells at 1 microM
      concentration, which is a mode of action that might further contribute to its
      hepatocarcinogenicity. The present data seem to suggest that the AhR activation,
      induction of enzymes involved in metabolic activation, inhibition of GJIC or
      stimulation of cell proliferation might all contribute to the hepatocarcinogenic
      effects of DBC and DiMeDBC.

PMID- 16406434
TI  - Imaging liver metastases: review and update.
AB  - The radiologic diagnosis of liver metastasis involves detection,
      characterization, and tumor staging. Knowledge of the histopathologic changes
      that occur with metastases provides the best approach to the accurate
      interpretation of radiologic imaging findings, and in particular, radiologists
      need to choose appropriate imaging methods based on such knowledge. Because the
      majority of metastases are hypovascular, the merits of the routine acquisition of
      hepatic arterial dominant-phase images by contrast-enhanced computed tomography
      (CT) or magnetic resonance imaging (MRI) are disputable. Hepatic arterial
      dominant-phase images may be obtained when hypervascular tumors are suspected or
      three-dimensional CT angiography is necessary. And, imaging during the portal
      venous phase is essential for detecting metastases, evaluating intrahepatic
      vessel invasion, and for assessing intratumoral necrosis or fibrosis. Equilibrium
      to delayed-phase imaging 3-5 min after contrast administration may improve the
      detection of intratumoral fibrosis, and occasionally lead to more accurate tissue
      characterization. MRI offers diagnostic information on vascularity, amount of
      free water, hemorrhage, fibrosis, necrosis, and water molecule diffusion in
      metastases. And, liver-specific contrast agents like superparamagnetic iron
      oxide, liposoluble gadolinium chelate, and manganese may improve the MRI-based
      diagnosis of liver metastases.

PMID- 16406435
TI  - Ultrasonographic measurement of subarachnoid space in normal term newborns.
AB  - This study was conducted in order to assess the normal range of subarachnoid
      space width in healthy term newborns. A total of 230 healthy newborns were
      evaluated within the first 28 days of life. Measurements were correlated with
      body weight, height and head circumference. Mean measurements for falx-cortex and
      craniocortical widths and the correlations are given in tables. Subarachnoid
      space widths increased as weight, height and head circumference increased and the
      correlation was statistically significant.

PMID- 16406436
TI  - Normal renal development investigated with fetal MRI.
AB  - OBJECTIVE: To evaluate age-dependent changes in fetal kidney measurements with
      MRI. PATIENTS AND METHODS: Fetal MRI examinations were used to study the kidney
      length (218 fetuses), signal intensities of renal tissue, renal pelvis, and liver
      tissue on T2-weighted images (223 fetuses), and the whole-kidney apparent
      diffusion coefficient (107 fetuses). A 1.5 T superconducting unit with a phased
      array coil was used in patients from 16 to 39 weeks' gestation. The imaging
      protocol included T2-weighted single-shot fast spin-echo, T2-weighted balanced
      angiography and diffusion-weighted sequences. Slice thickness ranged from 3 to
      5mm. RESULTS: Fetal kidney length as a function of gestational age was expressed
      by the linear regression: kidney length (mm)=0.190 x gestational age (d) -8.034
      (R(2) = 0.883, p < 0.001). Paired t-test analysis showed a highly statistically
      significant difference between the ratio of renal tissue signal intensity to
      renal pelvis signal intensity and the ratio of liver signal intensity to renal
      pelvis signal intensity on T2-weighted images (t = -50.963, d.f. = 162, p <
      0.001), with renal tissue hyperintense to liver tissue. The apparent diffusion
      coefficient in relation to gestational age was described by the equation: ADC
      (microm(2)/s) = 0.0302 x square (gestational age (d)) -14.202 x gestational age
      (d) +2,728.6 (R(2) = 0.225, p < 0.001). CONCLUSION: The length, signal intensity
      on T2-weighted images, and apparent diffusion coefficient of the fetal kidney
      change significantly with gestational age. The presented data may help in the
      prenatal diagnosis of renal anomalies.

PMID- 16406437
TI  - Fetal magnetic resonance imaging and human genetics.
AB  - The use of fetal magnetic resonance imaging (MRI), in addition to prenatal
      genetic testing and sonography, has the potential to improve prenatal diagnosis
      of genetic disorders. MRI plays an important role in the evaluation of fetal
      abnormalities and malformations. Fetal MRI often enables a differential
      diagnosis, a determination of the extent of the disorder, the prognosis, and an
      improvement in therapeutic management. For counseling of parents, as well as to
      basically understand how genetic aberrations affect fetal development, it is of
      great importance to correlate different genotypes with fetal MRI data.

PMID- 16406438
TI  - Fetal MR.

PMID- 16406439
TI  - Fetal MRI in experimental tracheal occlusion.
AB  - Congenital diaphragmatic hernia (CDH) is associated with a high mortality, which
      is mainly due to pulmonary hypoplasia and secondary pulmonary hypertension. In
      severely affected fetuses, tracheal occlusion (TO) is performed prenatally to
      reverse pulmonary hypoplasia, because TO leads to accelerated lung growth.
      Prenatal imaging is important to identify fetuses with pulmonary hypoplasia, to
      diagnose high-risk fetuses who would benefit from TO, and to monitor the effect
      of TO after surgery. In fetal imaging, ultrasound (US) is the method of choice,
      because it is widely available, less expensive, and less time-consuming to
      perform than magnetic resonance imaging (MRI). However, there are some
      limitations for US in the evaluation of CDH fetuses. In those cases, MRI is
      helpful because of a better tissue contrast between liver and lung, which enables
      evaluation of liver herniation for the diagnosis of a high-risk fetus. MRI
      provides the ability to determine absolute lung volumes to detect lung
      hypoplasia. In fetal sheep with normal and hyperplastic lungs after TO, lung
      growth was assessed on the basis of cross-sectional US measurements, after
      initial lung volume determination by MRI. To monitor fetal lung growth after
      prenatal TO, both MRI and US seem to be useful methods.

PMID- 16406440
TI  - Cleaning validation 1: development and validation of a chromatographic method for
      the detection of traces of LpHse detergent.
AB  - A high performance liquid chromatography (HPLC) method for the detection of
      traces of LpHse (4-tert-amylphenol and 2-phenylphenol) has been developed and
      validated. The method was shown to be linear in the range from 0.5 to 10.00 ppm
      in solution. The method was also shown to be accurate with a recovery of up to
      95% by area response for amylphenol and up to 94% by area response for
      phenylphenol from metal surfaces (4''x4'' un-polished 304 stainless steel plates)
      by means of swab material. The reproducibility of the method was determined to be
      1.61% by area response and 1.52% by height response for amylphenol and 5.40% by
      area response and 13.77% by height response for phenylphenol from solutions
      reported as the pooled relative standard deviation. The developed method was also
      shown to be rugged by comparisons of different preparations by different
      analysts. The limit of detection was established to be 0.076 ppm by peak area,
      0.079 ppm by peak height for amylphenol and 0.34 ppm by peak area, 0.82 ppm by
      peak height for phenylphenol from solution, and 1.77 ppb by peak area, 1.23 ppm
      by peak height for amylphenol and 1.23 ppm by peak area, 1.44 ppm by peak height
      for phenylphenol from recovery from metal studies. The limit of quantitation was
      established to be 0.25 ppm by peak area, 0.26 ppm by peak height for amylphenol
      and 1.14 ppm by peak area, 2.73 ppm by peak height for phenylphenol from
      solution, and 3.89 ppm by peak area, 4.11 ppm by peak height for amylphenol and
      4.11 ppm by peak area, 4.79 ppm by peak height for phenylphenol from recovery
      from metal plates studies. This method can be employed to determine the presence
      of LpHse residues in cleaned equipments where the detergent was used.

PMID- 16406441
TI  - Analysis of condensed and hydrolysable tannins from commercial plant extracts.
AB  - High performance liquid chromatography (HPLC)/DAD and MS qualitative and
      quantitative analyses of polyphenols, hydrolysable and condensed tannins from
      Pinus maritima L. and tannic acid (TA) extracts were performed using normal and
      reverse phase. Normal-phase HPLC was more suitable for pine bark (PBE) and tannic
      acid extracts analysis. The chromatographic profile revealed that P. maritima L.
      extract was mainly composed by polymeric flavanols (containing from two to seven
      units) and tannic acid (characterized by a mixture of glucose gallates containing
      from three to seven units of gallic acid). Concerning their antimycotic
      properties, P. maritima L. extract exhibited a broad activity towards yeast
      strains of the genera Candida, Cryptococcus, Filobasidiella, Issatchenkia,
      Saccharomyces: MICs from 200 to 4000 microg/ml (corresponding to 140-2800
      microg/ml of active polyphenols) were determined. Conversely, no activity of
      tannic acid was observed over the same target microorganisms. Taken into
      consideration the above results of HPLC analysis and on the basis of the current
      literature, we may conclude that only 70.2% of polyphenols (recognized as
      condensed tannins) occurring in P. maritima L. extract can be apparently
      considered responsible for its antimycotic activity.

PMID- 16406442
TI  - A rapid LC/MS/MS quantitation assay for naringin and its two metabolites in rats
      plasma.
AB  - Naringin is a flavonoid that exists in many plants and traditional Chinese
      medicines. In this study, a highly sensitive and specific electrospray ionization
      (ESI) liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was
      developed for quantification of naringin and its two metabolites, naringenin and
      naringenin glucuronide. Naringin and naringenin were extracted from rat plasma
      with ethyl acetate, using hesperidin as an internal standard. Components in the
      extract were separated on a 100 mm x 2.0 mm Betabasic 5 microm C18 ODS column by
      isocratic elution with 70% methanol. The components were analyzed in the multiple
      reaction-monitoring (MRM) mode in the precursor/product ion pair of m/z
      581.3/273.4 for naringin, m/z 273.4/153.1 for naringenin and m/z 611.5/303.4 for
      hesperidin, respectively. Linear calibration curves were obtained in the range of
      5-1000 ng/ml, using 0.1 ml rat plasma. The within-day coefficients of variation
      (CVs) were 3.1, 1.8 and 2.2% for naringin, 3.0, 3.3, 3.1% for naringenin at 5, 50
      and 500 ng/ml (n=5). The between-day CVs were 3.4, 1.7 and 4.9% for naringin and
      4.0, 3.0, 4.6% for naringenin (n=5) at 5, 50 and 500 ng/ml respectively. A
      formulation based on PEG400 was used and orally administered to Sprague-Dawley
      male rats. Plasma drug concentrations were measured by this method and the
      pharmacokinetics was analyzed by WinNonlin computer software. Plasma
      concentration-time profiles of naringin were found to increase quickly and
      decline rapidly within 2 h and could not be detected after 24 h. Naringenin and
      naringenin glucuronide occurred slower and the T(max) were about 9 and 7.5 h
      later, respectively.

PMID- 16406443
TI  - Molecular lipophilicity determination of a huperzine series by HPLC: comparison
      of C18 and IAM stationary phases.
AB  - Two hydrophobic parameters (logkw-C18 and logkw-IAM, respectively) of a huperzine
      A series were extrapolated by high performance liquid chromatography (HPLC) using
      both C18 and immobilised artificial membrane (IAM) columns. A mathematical
      correlation between C18 and IAM hydrophobic parameters was completed, suggesting
      a similar behaviour on both columns. This behaviour was principally led by
      hydrophobic forces. The theoretical lipophilicity (logP) of each compound was
      computed using Pallas software and compared to experimental values, showing a
      similar lipophilic behaviour. Finally, the huperzine logkw-IAM and logkw-C18
      values were correlated with the relative bound percentage of huperzine in human
      serum albumin, confirming that hydrophobic forces are predominant in the
      huperzine-HSA binding mechanism.

PMID- 16406444
TI  - Consolidation of auditory cortex-dependent memory requires N-methyl-D-aspartate
      receptor activation.
AB  - The pharmacological basis of sensory cortex-dependent learning and associated
      cortical reorganizations is only partially understood. In the Mongolian gerbil,
      the auditory cortex is critical for discriminating the directions of modulation
      of linearly frequency-modulated tones (FMs). To examine the role of N-methyl-D
      aspartate (NMDA)-type glutamate receptors in FM discrimination learning,
      selective antagonists were used. Compared to vehicle-treated controls, both
      systemic administration of MK-801 before but not after training, and infusion of
      D-AP-5 into the auditory cortex after training caused retention deficits
      detectable 24h later. The amnesic actions were reversible and in a close temporal
      relation to memory formation. Acquisition performance and performance of an
      established FM discrimination reaction were not affected. These findings suggest
      that NMDA receptor activation is required for long-term memory consolidation in
      auditory cortex-dependent learning.

PMID- 16406445
TI  - The GABA(B) receptor allosteric modulator CGP7930, like baclofen, reduces operant
      self-administration of ethanol in alcohol-preferring rats.
AB  - GABA systems have been implicated as targets for ethanol at the cellular,
      molecular and behavioural level. The present study was designed to further
      examine the potential of the GABA(B) receptor as a target for regulating operant
      alcohol responding. Given that the prototypic agonist, baclofen, reduces the self
      administration of alcohol, we hypothesized that the GABA(B) receptor allosteric
      modulator, CGP7930, might have similar actions but a reduced side-effect profile.
      In this context, inbred alcohol-preferring (iP) rats were trained to respond for
      10% v/v ethanol in a fixed ratio paradigm; all drug testing was performed under
      an FR3 schedule. Both baclofen and CGP7930 independently reduced voluntary
      responding for 10% ethanol in a dose-related manner. Neither drug impacted upon
      responding for water. A combination of subthreshold doses of baclofen and CGP7930
      was also able to reduce operant responding for ethanol, suggesting that CGP7930
      is indeed acting to facilitate GABA(B) receptor-mediated signalling in this
      paradigm. These data demonstrate the potential of positive allosteric modulators
      of metabotropic GABA(B) receptors to regulate alcohol responding.

PMID- 16406446
TI  - Optimization of the separation of some psychotropic drugs and their respective
      metabolites by liquid chromatography.
AB  - A chemometric procedure is described to optimize the separation of some drugs
      used in the treatment of psychotic disorders: haloperidol, levomepromazine,
      risperidone, venlafaxine, carbamazepine and their main metabolites: reduced
      haloperidol, 9-hydroxy risperidone, desmethyl levomepromazine, desmethyl
      venlafaxine. The purpose of the procedure is the unambiguous identification and
      detection in biological fluids. Isocratic reversed-phase liquid chromatography
      with diode array detection was utilized. An experimental design methodology was
      carried out in which the experimental response is selectivity. In this way the
      designs for mixture compounds and for process variables (five variables) was
      performed which produced 36 experiments to carry out. The desirability function
      was used to select optimum separation conditions. The procedure provides a
      chromatogram of well separated solutes.

PMID- 16406447
TI  - Construction of universal quantitative models for determination of roxithromycin
      and erythromycin ethylsuccinate in tablets from different manufacturers using
      near infrared reflectance spectroscopy.
AB  - Universal quantitative models using NIR reflectance spectroscopy were developed
      for the analysis of API contents (active pharmaceutical ingredient) in
      roxithromycin and erythromycin ethylsuccinate tablets from different
      manufacturers in China. The two quantitative models were built from 78 batches of
      roxithromycin samples from 18 different manufacturers with the API content range
      from 19.5% to 73.9%, and 66 batches erythromycin ethylsuccinate tablets from 36
      manufacturers with the API content range from 28.1% to 70.9%. Three different
      spectrometers were used for model construction in order to have robust and
      universal models. The root mean square errors of cross validation (RMSECV) and
      the root mean square errors of prediction (RMSEP) of the model for roxithromycin
      tablets were 1.84% and 1.45%, respectively. The values of RMSECV and RMSEP of the
      model for erythromycin ethylsuccinate tablets were 2.31% and 2.16%, respectively.
      Based on the ICH guidelines and characteristics of NIR spectroscopy, the
      quantitative models were then evaluated in terms of specificity, linearity,
      accuracy, precision, robustness and model transferability. Our study has shown
      that it is feasible to build a universal quantitative model for quick analysis of
      pharmaceutical products from different manufacturers. Therefore, the NIR method
      could be used as an effective method for quick, non-destructive inspection of
      medicines in the distribution channels or open market.

PMID- 16406448
TI  - Simultaneous effect of cyclodextrin complexation, pH, and hydrophilic polymers on
      naproxen solubilization.
AB  - The effect of pH variation on complexation and solubilization of naproxen (pK(a)
      4.2) with natural betaCyclodextrin (betaCyD) and various neutral, cationic and
      anionic betaCyD-derivatives has been investigated. The combined effect of pH
      variation and hydrophilic polymer addition on CyD solubilizing and complexing
      efficiency has also been determined. Phase-solubility analysis in buffered
      aqueous solutions (pH from 1.1 to 6.5) was used to study the interaction of the
      drug with each CyD, in the presence or not of the water-soluble polymer. A clear
      influence of the substituent type was observed, the methylderivative being the
      most efficient agent; on the contrary, unexpectedly, no influence of the CyD
      charge in the interaction with the ionizable drug was detected. As expected,
      total drug solubility increased with increasing pH; however, the solubility
      increment with respect to drug alone obtained by CyD complexation progressively
      decreased, with a parallel reduction of the complex stability, attributed to the
      reduced affinity of charged drug for the hydrophobic CyD cavity. The addition of
      the polymer in part counterbalanced the destabilizing effect obtained with
      increasing pH, by improving the CyD complexation power towards naproxen. In
      particular, the presence of PVP allowed an increase of the complex stability
      constant with hydroxypropyl betaCyD up to 60% with respect to the corresponding
      drug-CyD binary system. Therefore, the combined strategy of pH control and
      polymer addition to the CyD complexing medium can be successfully exploited to
      improve naproxen solubilization and reduce the amount of CyD needed. The
      construction of theoretical drug solubility curves as a function of pH for any
      given CyD and polymer concentration enables selection of the best experimental
      conditions for obtaining the desired drug solubility value.

PMID- 16406449
TI  - A critical study on the application of the zero-crossing derivative
      spectrophotometry to the photodegradation monitoring of lacidipine.
AB  - An extensive study on the application of the "zero-crossing" technique for the
      analysis of a binary mixture of the photosensitive drug lacidipine and its
      corresponding by-product by derivative spectrophotometry is described. The
      technique has been compared to either conventional and recently developed UV
      spectrophotometric procedures, including chemometric methods. The prediction
      ability of the different analytical techniques has been checked by using the
      first-order derivative spectra of drug and photoproduct in binary mixtures.
      Relative advantages and drawbacks have been discussed. The zero-crossing
      technique suffers from several limitations, mostly ascribed to the selection of
      suitable signals along slopes of the spectral curve, giving rise to low accurate
      and precise results. The mean recovery from the zero-crossing analysis was
      calculated to lie in the 95.1-98.4% range for lacidipine, and 91.2-118.9% for the
      photoproduct. Chemometric methods showed a greater prediction ability with a
      101.4-103.0% and 96.3-98.4% recovery for drug and degradation product,
      respectively.

PMID- 16406450
TI  - Determination of clopidogrel metabolite (SR26334) in human plasma by LC-MS.
AB  - A new, sensitive, specific and reproducible method for determination of
      clopidogrel metabolite (SR26334) in human plasma has been developed. After liquid
      liquid extraction on Chem Elut cartridges with dichloromethane, samples were
      quantified using reversed-phase high performance liquid chromatography with mass
      detection. The determination was performed on a Luna C18, 3 microm (75 mmx4.6 mm
      i.d.) column with an acetonitrile-water-formic acid mixture (60:40:0.1, v/v/v) as
      a mobile phase. The flow rate was set at 0.2 mL/min. Repaglinide was chosen as an
      internal standard and the time of analysis was 12 min. For SR26334 the limits of
      detection and quantification were 7.5 ng/mL and 20 ng/mL, respectively, and the
      calibration curve was linear up to 3000 ng/mL. The extraction recovery of SR26334
      from plasma was within the range of 85-90%. The method has been successfully used
      to study clopidogrel metabolite pharmacokinetics in healthy volunteers.

PMID- 16406451
TI  - Development and validation of a simple reversed-phase high-performance liquid
      chromatography method for the determination of testosterone in serum of males.
AB  - An isocratic high-performance liquid chromatographic method with detection at 234
      nm was developed, optimized and validated for the determination of testosterone
      in human serum. Propylparaben was used as internal standard. A Hypersil BDS RP
      C18 column (150 mmx4.6 mm, 5 microm), was equilibrated with a mobile phase
      composed of acetonitrile and water (35:65, v/v) and having a flow rate of 1
      ml/min. The elution time for testosterone and internal standard was approximately
      11.6 and 9.9 min, respectively. Calibration curves of testosterone in serum were
      linear in the concentration range of 1-20 ng/ml. Limits of detection and
      quantification in serum were 0.4 and 1.1 ng/ml, respectively. Recovery was
      greater than 92%. Intra- and inter-day relative standard deviation for
      testosterone in serum was less than 2.1 and 3.9%, respectively. This method was
      applied to the determination of testosterone serum levels of 12 healthy males and
      data were correlated with data obtained using a radioimmunoassay method.

PMID- 16406452
TI  - Development of a faster determination of 10 anabolic steroids residues in animal
      muscle tissues by liquid chromatography tandem mass spectrometry.
AB  - A method had been developed for determination of residues of 10 anabolic steroids
      (ASs) in animal muscle tissues by liquid chromatography tandem mass spectrometry
      (LC/MS/MS). After enzymolysis, the sample was extracted with tert-butyl methyl
      ether, cleaned up through reverse solid-phase extraction and further determined
      by LC/MS/MS under multiple reaction monitoring (MRM) mode. The limits of
      detection (LOD) of LC/MS/MS method used for testing epitestosterone (ETS),
      nandrolone (17 beta-NT), 17 alpha-methyl-testosterone (MTS), testosterone 17
      propionate (PTS), medroxyprogesterone (MED), progesterone (PG), estrone (ESN), 17
      beta-estradiol (17 beta-ES), 17alpha-ethynylestradiol (EES) and estriol (EST) in
      animal muscle ranged from 0.06 to 0.22 microg/kg, and the limits of
      quantification (LOQ) were from 0.12 to 0.54 microg/kg. Experiments on spiked
      samples of pork, beef, chicken and fish showed that at addition level of 1.0
      microg/kg, the average recoveries of the ASs ranged from 64% to 77%, and
      coefficients of variation from 7.1% to 20.3%, while at addition level of 2.0
      microg/kg, the average recoveries ranged from 70% to 89%, and coefficient of
      variation from 7.1% to 19.1%.

PMID- 16406453
TI  - The determination of nicotinic acid in plasma by mixed-mode liquid chromatography
      tandem mass spectrometry following ion exchange solid phase extraction.
AB  - An assay for nicotinic acid in plasma samples has been developed using ion
      exchange solid phase extraction in 96-well format followed by mixed-mode ion
      exchange/reversed-phase liquid chromatography with positive ion tandem mass
      spectrometry detection. The assay avoids the need for time-consuming
      derivatisation procedures or involatile ion-pair chromatography reagents. The
      assay is linear over the wide range 0.05-20 microg/mL, based on a 100 microL
      sample (correlation coefficient>0.99). The assay is accurate and precise (bias
      and coefficient of variation<18%) over this calibration range.

PMID- 16406454
TI  - Transfer of NIR calibrations for pharmaceutical formulations between different
      instruments.
AB  - In order to evaluate how well existing techniques for transferring NIR
      calibrations perform for solid pharmaceutical formulations, a study on four
      assays of active ingredients was undertaken. The study included two
      configurations of dispersive NIR instruments and one Fourier transform (FT)
      instrument. Three methods for calibration transfer: slope/bias correction, local
      centring and piecewise direct standardisation (PDS), were tested and evaluated.
      Our conclusions are that the calibration transfer methods tested can perform
      equally well. It was shown that it is possible to transfer calibrations between
      instruments of different configurations or even of different types, without
      loosing the prediction ability of the calibration. To achieve a good calibration
      transfer, a larger variation in the content of the active ingredient in the
      samples and more samples are needed for the slope and bias correction method
      compared to the local centring method. For PDS to be a successful calibration
      transfer method, an optimisation of the number of transfer samples and how they
      are selected together with various factors specific for this method is needed.
      Local centring is the preferred transfer method as its performance is excellent
      yet it is simple to perform, no optimisation is needed, only a few transfer
      samples are required and the transfer samples do not have to vary in their
      content of the active ingredient.

PMID- 16406455
TI  - Determination of homovanillic acid (HVA) in human plasma by HPLC with coulometric
      detection and a new SPE procedure.
AB  - A sensitive high-performance liquid chromatographic method has been developed for
      the determination of homovanillic acid (HVA), the main metabolite of dopamine, in
      human plasma. Analyses were carried out on a reversed-phase column (C8, 250 mm x
      4.6 mm i.d., 5 microm) using a mobile phase composed of 10% methanol and 90%
      aqueous citrate buffer, containing octanesulfonic acid and EDTA at pH 4.8.
      Coulometric detection was used, setting the guard cell at +0.100 V, the first
      analytical cell at -0.200 V and the second analytical cell at +0.500 V. A careful
      solid-phase extraction procedure, based on strong anion exchange (SAX) cartridges
      (100 mg, 1 mL), was implemented for the pre-treatment of plasma samples.
      Extraction yield was satisfactory, being the mean value 98.0%. The calibration
      curve was linear over the concentration range of 0.2-25.0 ng mL(-1) of
      homovanillic acid. The limit of quantitation (LOQ) was 0.2 ng mL(-1) and the
      limit of detection (LOD) was 0.1 ng mL(-1). The method was successfully applied
      to plasma samples from former alcohol, cocaine and heroin addicts. Results were
      satisfactory in terms of precision and accuracy. Hence, the method is suitable
      for the determination of homovanillic acid in human plasma.

PMID- 16406457
TI  - West Nile virus infection of the placenta.
AB  - Intrauterine infection of fetuses with West Nile virus (WNV) has been implicated
      in cases of women infected during pregnancy. Infection of timed-pregnant mice on
      5.5, 7.5, and 9.5 days post-coitus (dpc) resulted in fetal infection. Infection
      of dams on 11.5 and 14.5 dpc resulted in little and no fetal infection,
      respectively. Pre-implantation embryos in culture were also infected with WNV
      after the blastocyst stage and the formation of trophectoderm. Green fluorescent
      protein (GFP) expression was observed in a trophoblast stem (TS) cell line after
      infection with a GFP-expressing WNV construct. However, no fluorescence was
      observed in differentiated trophoblast giant cell (TGC) cultures. GFP
      fluorescence was present in TGC cultures if infected TS cells were induced to
      differentiate. These results suggest that embryos are susceptible to WNV
      infection after the formation of the trophectoderm around 3.5 dpc through the
      formation of the functional placenta around 10.5 dpc.

PMID- 16406456
TI  - Regulation of the expression of the Epstein-Barr virus early gene BFRF1.
AB  - The switch from latency to lytic phase of Epstein-Barr virus (EBV) is coordinated
      by the expression of two viral transactivators known as ZEBRA and RTA. The BFRF1
      gene has been shown to be transcribed during the early phases of EBV lytic cycle.
      Here, we characterized the BFRF1 promoter showing that ZEBRA transfection
      stimulated BFRF1 expression, whereas RTA induced BFRF1 only after the
      transfection of an amount of plasmid largely in excess than that sufficient to
      stimulate the expression of other RTA-responsive genes. However, a co-operative
      effect between ZEBRA and RTA in the expression of BFRF1 is evident since the
      transfection of RTA can rescue the transactivating capacity of a mutant of the
      ZEBRA protein, known as Z(S186A), that has a substitution affecting the DNA
      binding region. Moreover, we identified one ZEBRA-responsive element (ZRE) and
      one RTA-responsive element (RRE) within the BFRF1 promoter region.

PMID- 16406458
TI  - Deletion of a Cys-His motif from the Alpharetrovirus nucleocapsid domain reveals
      late domain mutant-like budding defects.
AB  - The Rous sarcoma virus (RSV) Gag polyprotein is the only protein required for
      virus assembly and release. We previously found that deletion of either one of
      the two Cys-His (CH) motifs in the RSV nucleocapsid (NC) protein did not abrogate
      Gag-Gag interactions, RNA binding, or packaging but greatly reduced virus
      production (E-G. Lee, A. Alidina et al., J. Virol. 77: 2010-2020, 2003). In this
      report, we have further investigated the effects of mutations in the CH motifs on
      virus assembly and release. Precise deletion of either CH motif, without
      affecting surrounding basic residues, reduced virus production by approximately
      10-fold, similar to levels seen for late (L) domain mutants. Strikingly,
      transmission electron microscopy revealed that virions of both DeltaCH1 and
      DeltaCH2 mutants were assembled normally at the plasma membrane but were arrested
      in budding. Virus particles remained tethered to the membrane or to each other,
      reminiscent of L domain mutants, although the release defect appears to be
      independent of the L domain functions. Therefore, two CH motifs are likely to be
      required for budding independent of a requirement for either Gag-Gag interactions
      or RNA packaging.

PMID- 16406459
TI  - Transcription of potato spindle tuber viroid by RNA polymerase II starts in the
      left terminal loop.
AB  - Viroids are single-stranded, circular RNAs of 250 to 400 bases, that replicate
      autonomously in their host plants but do not code for a protein. Viroids of the
      family Pospiviroidae, of which potato spindle tuber viroid (PSTVd) is the type
      strain, are replicated by the host's DNA-dependent RNA polymerase II in the
      nucleus. To analyze the initiation site of transcription from the (+)-stranded
      circles into (-)-stranded replication intermediates, we used a nuclear extract
      from a non-infected cell culture of the host plant S. tuberosum. The (-)-strands,
      which were de novo-synthesized in the extract upon addition of circular (+)
      PSTVd, were purified by affinity chromatography. This purification avoided
      contamination by host nucleic acids that had resulted in a misassignment of the
      start site in an earlier study. Primer-extension analysis of the de novo
      synthesized (-)-strands revealed a single start site located in the hairpin loop
      of the left terminal region in circular PSTVd's secondary structure. This start
      site is supported further by analysis of the infectivity and replication behavior
      of site-directed mutants in planta.

PMID- 16406461
TI  - Implications of process evaluation for clinical effectiveness and clinical
      practice in a trial on chronic shoulder complaints.
AB  - OBJECTIVE: The intervention process was evaluated in a randomised clinical trial
      on the effectiveness of a behavioural Graded Exercise Therapy (GET) programme for
      patients with chronic shoulder complaints in primary care settings. This process
      evaluation was done for three reasons: first, to know whether the programme was
      performed as planned; second, to know whether or not this treatment is feasible
      in normal practice; third, to identify needs for improvement of the protocol to
      facilitate implication. METHODS: We evaluated the extent to which the programme
      is being applied according to protocol, patient adherence to the programme and
      the suitability of the programme according to patients and physiotherapists.
      Twenty participating physiotherapists and 87 patients allocated to GET were asked
      to evaluate the intervention process. Furthermore, a sample of 10 patients, taken
      from the total number of 87 patients allocated to GET, was invited to take part
      in a focus group interview at the end of the study. We evaluated the intervention
      process using a treatment registration form filled in by the physiotherapists
      during treatment, evaluation forms filled in independently by physiotherapists
      and patients 26 weeks after the start of the treatment period, and information
      gathered during the focus group interview at the end of the study. RESULTS: GET
      was applied according to protocol to an acceptable extent, and participating
      patients showed satisfactory adherence to the programme. CONCLUSIONS: Clinical
      effectiveness of GET in this trial is not influenced by flaws in the application
      of the programme or by lack of patient adherence. PRACTICE IMPLICATIONS: The
      programme could be improved in terms of the process of goal-setting, and the
      implementation of GET could be facilitated if the programme is embedded in a
      multidisciplinary approach in primary care.

PMID- 16406460
TI  - HIV-1 subtype C in vitro growth and coreceptor utilization.
AB  - Human immunodeficiency virus type 1 subtype C (HIV-1C) accounts for about 50% of
      all HIV infections in the pandemic and is the predominant subtype in the heavily
      burdened region of southern Africa. HIV-1C possesses unique genetic and
      phenotypic features that might be associated with biological differences compared
      to other subtypes. Here, we generated virus isolates from individuals at
      different stages of HIV-1C infection and investigated the chemokine receptor
      repertoire that the derived HIV-1C isolates may utilize for entry. Our results
      show that the R5 phenotype predominates among viruses in Botswana, with a lesser
      contribution of viruses showing the dualtropic X4R5 phenotype. No viruses of pure
      X4 phenotype were found, which suggests no discernable evolution of HIV-1C to a
      monotropic X4 phenotype as the epidemic ages in Botswana. Usage of other
      coreceptors was rare and apparently insignificant. These results enhance our
      understanding of HIV-1C biology, with implications for designing and testing
      therapeutic and prophylactic agents.

PMID- 16406462
TI  - Development and communication of written ethics policies on euthanasia in
      Catholic hospitals and nursing homes in Belgium (Flanders).
AB  - OBJECTIVE: To describe whether and how Catholic hospitals and nursing homes in
      Belgium (Flanders) have developed written ethics policies on euthanasia and
      communicated these policies to their employees, patients, and patient's
      relatives. METHODS: A cross-sectional mail survey of general directors of
      Catholic hospitals and nursing homes in Belgium (Flanders). RESULTS: Of the 298
      targeted institutions, 81% of hospitals and 62% of nursing homes returned
      complete questionnaires. A high percentage of Catholic hospitals (79%) and a
      moderate percentage of nursing homes (30%) had written ethics policies on
      euthanasia. Both caregivers and healthcare administrators were involved in the
      development and approval of these policies. Physicians and nurses were best
      informed about the policies. More than half of the nursing homes (57%) took the
      initiative to inform both residents and relatives about the policies, while only
      one hospital did so. CONCLUSION: The high prevalence of written ethics policies
      on euthanasia in Flemish Catholic hospitals may reflect the concern of healthcare
      administrators to maintain the quality of care for patients requesting
      euthanasia. However, the true contribution of these policies to quality end-of
      life care and to supporting caregivers remains unknown and needs further
      research. PRACTICE IMPLICATIONS: Legislation and centrally developed guidelines
      might influence healthcare institutions to develop ethics policies.

PMID- 16406463
TI  - Communication with patients during the prenatal testing procedure: an explorative
      qualitative study.
AB  - OBJECTIVE: While generally two phases of prenatal genetic counseling are
      distinguished, i.e. pre- and post-test counseling, we revealed a third form of
      communication during the testing procedure. The content of this intermediate
      communication was explored. METHODS: A secondary analysis was performed on data
      obtained in another observational study, which was focussed on how indefinite
      testing results are clarified. Thirteen testing trajectories in which
      communication with parents took place during the testing procedure were further
      analysed. RESULTS: In the majority of cases the content of intermediate
      communication was similar to the content of pre-test counseling. In four cases
      the content was different, because the communication involved the parents in
      decision-making about a testing result, which was still being processed.
      CONCLUSION: Communication in (prenatal) genetic testing is not always restricted
      to separate phases, but can be an ongoing process occurring parallel to, and
      sometimes even intertwined with, the testing process. The advocated model of
      shared decision-making might work better once it is determined if the decision
      concerns the area wherein the provider is the expert, or the patient. PRACTICE
      IMPLICATIONS: Further research into the process of continuing decision-making
      could clarify how providers' and patients' responsibilities regarding the
      diagnostic process are distributed. Meanwhile, the possible occurrence of
      continuous decision-making should be mentioned in (prenatal) genetic counseling.

PMID- 16406464
TI  - Patient participation in the consultation process: a structured review of
      intervention strategies.
AB  - OBJECTIVE: To describe the range and effectiveness of intervention strategies
      designed to enhance patient participation in the consultation process. METHODS: A
      systematic review of published literature (1976-2004) was undertaken. Controlled
      trials in English were included. Data regarding study design, intervention
      characteristics, patient populations and study results were extracted. RESULTS:
      One hundred and forty-six articles describing 137 trials were reviewed. A
      pragmatic categorisation of intervention strategies and study outcomes supported
      data synthesis. Patient-targeted coaching and educational materials, and provider
      targeted communication skills training have a substantial impact on
      communication. Information feedback to providers from patient-reported outcome
      measures (PROMs) benefits provider diagnosis and management of patient
      conditions. Communication and provider diagnosis and management benefit most from
      the reviewed interventions. Although patient satisfaction and health status were
      two of the most frequently measured outcomes, overall, the interventions appeared
      to have less impact on patient self-efficacy, attitudes and behaviours, patient
      satisfaction, health status and resource use. CONCLUSION: Evidence is
      insufficient to strongly advocate one approach to enhancing patient participation
      in the consultation process. More rigorous research design with clearly specified
      intervention strategies and appropriately defined outcomes assessed over both the
      short and long term is required. PRACTICE IMPLICATIONS: Although limited and
      inconclusive, the most extensive and most encouraging evidence to enhance patient
      participation in the consultation process is available for three patient-targeted
      intervention strategies (coaching, educational materials and PROMs feedback to
      providers) and one provider-targeted intervention strategy (communication skills
      training).

PMID- 16406465
TI  - Flavour formation by amino acid catabolism.
AB  - Microbial catabolism of amino acids produces flavour compounds of importance for
      foods such as cheese, wine and fermented sausages. Lactic acid bacteria are
      equipped with enzyme systems for using the amino acids in their metabolism and
      are useful for flavour formation of foods. Branched-chain amino acids (Leu, Ile,
      Val) are converted into compounds contributing to malty, fruity and sweaty
      flavours; catabolism of aromatic amino acids (Phe, Tyr, Trp) produce floral,
      chemical and faecal flavours; aspartic acid (Asp) is catabolised into buttery
      flavours and sulphuric amino acids (Met, Cys) are transferred into compounds
      contributing to boiled cabbage, meaty and garlic flavours.

PMID- 16406466
TI  - Regulation of dietary energy level and oil source on leptin and its long form
      receptor mRNA expression of the adipose tissues in growing pigs.
AB  - Two experiments were conducted to evaluate the effects of dietary energy level
      and source of oil on leptin mRNA and long form leptin receptor (Ob-Rl) mRNA
      expression in dorsal, abdominal and visceral adipose tissues in young growing
      pigs. In experiment one, 15 barrows (initial body weight 15.0 kg) were used to
      examine the effects of dietary energy levels on leptin mRNA and Ob-Rl mRNA
      expression. The pigs were randomly allotted to one of three dietary treatments
      (n=5 per treatment) containing 13.4, 15.1 or 16.7 MJ DE/kg diet for 28 days.
      Based on the results of experiment one, experiment two was designed to examine
      the effects of oil sources including soybean oil (rich in n-6 polyunsaturated
      fatty acids) or fish oil (rich in n-3 polyunsaturated fatty acids) on leptin mRNA
      and Ob-Rl mRNA expression in the same adipose tissues examined in experiment one.
      The energy content of these diets was 15.1 MJ/kg. Fourteen barrows (initial
      weight 20.5 kg) were allocated to either of the two dietary treatments (n=7 per
      treatment), which was supplemented with either soybean or fish oil (both 5.73% of
      the diet) and fed to the pigs for 21 days. At the end of both experiments, blood
      samples were collected to determine plasma leptin and insulin concentrations.
      Adipose tissues were sampled to determine leptin and Ob-Rl mRNA expression using
      real-time fluorescence quantification PCR. In experiment one, plasma leptin
      concentrations were enhanced (P=0.02), and insulin concentrations were decreased
      (P<0.01) in pigs fed the high-energy diet (16.7 MJ DE/kg). Dorsal adipose tissue
      leptin mRNA expression was increased by feeding the diet containing 15.1 MJ/kg DE
      compared with the diets containing 13.4 and 16.7 MJ/kg DE. There was no
      difference in leptin mRNA expression in abdominal and visceral adipose tissue. In
      experiment two, there were no differences in plasma leptin and insulin
      concentrations between pigs fed with either fish oil or soybean oil diets.
      Nevertheless, fish oil decreased both leptin mRNA and Ob-Rl mRNA expression in
      dorsal adipose tissues compared with soybean oil (P<0.01). These experiments
      indicate that the source of oil plays a more potent role in regulation of leptin
      mRNA expression relative to dietary energy levels by an insulin-independent
      mechanism. Plasma leptin concentrations may also be regulated by a post
      transcriptional mechanism.

PMID- 16406467
TI  - Distorting visual space with sound.
AB  - Attentional repulsion is described as the perceived displacement of a vernier
      stimulus in a direction that is opposite to a brief peripheral visual cue (Suzuki
      & Cavanagh, 1997). Here, we demonstrate that visual repulsion can also be
      elicited using lateralized sounds. Given that repulsion is believed to be
      occurring in early retinotopic visual areas, these results raise the possibility
      that the location of a sound could directly influence the pattern of activity as
      early as primary visual cortex.

PMID- 16406468
TI  - XOR style tasks for testing visual object processing in monkeys.
AB  - Using visually complex stimuli, three monkeys learned visual exclusive-or (XOR)
      tasks that required detecting two way visual feature conjunctions. Monkeys with
      passive exposure to the test images, or prior experience, were quicker to acquire
      an XOR style task. Training on each pairwise comparison of the stimuli to be used
      in an XOR task provided nearly complete transfer when stimuli became intermingled
      in the full XOR task. Task mastery took longer, accuracy was lower, and response
      times were slower for conjunction stimuli. Rotating features of the XOR stimuli
      did not adversely effect recognition speed or accuracy.

PMID- 16406469
TI  - Cytoplasmic dynein/dynactin function and dysfunction in motor neurons.
AB  - The microtubule motor protein cytoplasmic dynein and its activator dynactin are
      essential in higher eukaryotes, due to critical roles in vesicular transport and
      cell division. Neurons are uniquely sensitive to defects in dynein/dynactin
      function, which affect retrograde axonal transport, neurotrophic factor
      signaling, neurofilament transport, mRNA localization, neuronal migration, and
      protein recycling and degradation. Mutations in either dynein or dynactin lead to
      motor neuron degeneration and loss. Recent progress in understanding the cellular
      mechanisms of dynein/dynactin function, and the effects of dynein/dynactin
      dysfunction has provided new insight into the roles of microtubule-based motility
      in the neuron.

PMID- 16406470
TI  - Zinc uptake is mediated by M1 muscarinic acetylcholine receptors in
      differentiated SK-SH-SY5Y cells.
AB  - Alzheimer's disease (AD), the most prevalent form of dementia, is characterized
      by several major morphological hallmarks such as senile plaques, neurofibrillary
      tangles and a loss of cholinergic basal forebrain neurons. Apart from cholinergic
      markers like choline acetyltransferase and acetylcholinesterase, there have been
      reports on changes in muscarinic acetylcholine receptors (mAChR) as well as on
      influences of zinc metabolism in the disease. As recent studies gave hints about
      a possible link between mAChRs and zinc uptake, the human neuroblastoma cell line
      SK-SH-SY5Y was used to evaluate the role of M1-mAChR on zinc uptake. Zinc levels
      were semi-quantitatively detected by using the zinc-specific fluorophor Zn-AF2
      DA. In the presence of 1 microM extracellular zinc, M1-mAChR stimulation with
      talsaclidine increased intracellular zinc levels as did stimulation of PKC by
      phorbol esters. Furthermore, the effect of extracellular zinc on the expression
      of the zinc finger protein PNUTS (protein phosphatase 1 nuclear targeting subunit
      10) was investigated and revealed an upregulation of PNUTS expression in the
      presence of 1 microM extracellular zinc by 294% when compared to incubation in
      zinc free medium. In summary, this report demonstrates that intracellular zinc
      uptake in SK-SH-SY5Y cells is controlled by M1-mAChR mediated signalling pathways
      and that zinc may act as a cofactor for transcriptional regulation of zinc finger
      genes such as PNUTS.

PMID- 16406471
TI  - Goal setting as a shared decision making strategy among clinicians and their
      older patients.
AB  - OBJECTIVE: Older adults are less likely than other age groups to participate in
      clinical decision-making. To enhance participation, we sought to understand how
      older adults consider and discuss their life and health goals during the clinical
      encounter. METHODS: We conducted six focus groups: four with community-dwelling
      older persons (n=42), one with geriatricians and internists (n=6), and one with
      rehabilitation nurses (n=5). Participants were asked to discuss: patients' life
      and health goals; communication about goals, and perception of agreement about
      health goals. Group interactions were tape-recorded, transcribed, and analyzed
      using content analysis. RESULTS: All participants were willing to discuss goals,
      but varied in the degree to which they did so. Reasons for non-discussion
      included that goal setting was not a priority given limited time, visits focused
      on symptoms, mutual perception of disinterest, and the presumption that all
      patients' goals were the same. CONCLUSION: Interventions to enhance goal setting
      need to address key barriers to promoting goals discussions. Participants
      recognized the benefits of goal setting, however, training and instruments are
      needed to integrate goal setting into medicine. PRACTICE IMPLICATIONS: Setting
      goals initially and reviewing them periodically may be a comprehensive, time
      efficient way of integrating patients' goals into their care plans.

PMID- 16406472
TI  - The diffusion of virtual communities in health care: concepts and challenges.
AB  - OBJECTIVE: This paper providers an overview and discussion of virtual communities
      in health care. Furthermore, we aim to discuss in this context ethical, legal and
      technical considerations and the current status of research in this domain.
      METHODS: We searched medical and social science literature including survey
      studies, randomized and non-randomized controlled interventions and reviews.
      RESULTS: The literature indicates that a virtual community in health care as a
      group of people using telecommunication with the purposes of delivering health
      care and education, and/or providing support, covers a wide range of clinical
      specialties, technologies and stakeholders. Examples include peer-to-peer
      networks, virtual health care delivery and research teams. Ethical challenges
      including the concepts of identity and deception, privacy and confidentiality and
      technical issues, such as sociability and usability are discussed. CONCLUSION:
      Virtual communities may empower patients and enhance coordination of care
      services; however, there is not sufficient systematic evidence of the
      effectiveness of virtual communities on clinical outcomes or patient empowerment.
      Researchers need to address issues, such as sample sizes and experimental design
      to further the research field in this domain. PRACTICE IMPLICATIONS: When
      practitioners utilize virtual community tools to communicate with patients or
      colleagues they have to maximize sociability and usability of this mode of
      communication, while addressing concerns for privacy and the fear of de
      humanizing practice, and the lack of clarity or relevance of current legislative
      frameworks.

PMID- 16406474
TI  - Patients using the Internet to obtain health information: how this affects the
      patient-health professional relationship.
AB  - OBJECTIVE: Health information is one of the most frequently sought topics on the
      Internet. A review of the literature was carried out to determine the use of the
      Internet for health information by the patient and how this could affect the
      patient-health professional relationship. METHODS: This study is a literature
      review, summarizing multiple empirical studies on a single subject and is not
      intended to be a meta-analysis. RESULTS: The review showed that the majority of
      health related Internet searches by patients are for specific medical conditions.
      They are carried out by the patient: (1) before the clinical encounter to seek
      information to manage their own healthcare independently and/or to decide whether
      they need professional help; (2) after the clinical encounter for reassurance or
      because of dissatisfaction with the amount of detailed information provided by
      the health professional during the encounter. CONCLUSION: There has been a shift
      in the role of the patient from passive recipient to active consumer of health
      information. Health professionals are responding to the more 'Internet informed'
      patient in one or more of three ways: (1) the health professional feels
      threatened by the information the patient brings and responds defensively by
      asserting their 'expert opinion' (health professional-centred relationship). (2)
      The health professional and patient collaborate in obtaining and analysing the
      information (patient-centred relationship). (3) The health professional will
      guide patients to reliable health information websites (Internet prescription).
      PRACTICE IMPLICATIONS: It is important that health professionals acknowledge
      patients' search for knowledge, that they discuss the information offered by
      patients and guide them to reliable and accurate health websites. It is
      recommended that courses, such as 'patient informatics' are integrated in health
      professionals' education.

PMID- 16406473
TI  - Communication and risk presentation in genetic counseling. Development of a
      checklist.
AB  - OBJECTIVE: Genetic counseling involves advising people about genetic disorders,
      genetic risks and preventive measures, and guiding them in the process of
      decision-making. It remains unclear what effect certain aspects of risk
      communication have on outcomes like risk perception and the decisions people
      take. In order to examine this relationship between process and outcomes, the
      present study aimed to develop a reliable checklist to assess aspects of risk
      communication in genetic counseling. METHODS: A preliminary checklist was
      developed on base of literature and tested for manageability in a pilot study.
      The checklist was adapted and tested for inter-observer reliability in 14 and 56
      genetic counseling sessions. Inter-observer reliability was measured by computing
      Kappa and proportions of agreement. RESULTS: Most of the items of the last
      version of the checklist had Kappa values between 0.4 and 1, which means that the
      inter-observer reliability for most items was sufficient or good. On the majority
      of items, the observers showed more than 80% agreement. CONCLUSION: The checklist
      we have developed has adequate inter-observer reliability and may be applied in
      future studies to assess risk communication aspects in genetic counseling.
      PRACTICE IMPLICATIONS: This checklist could be a useful instrument to identify
      the relationship between aspects of risk communication in genetic counseling and
      outcomes. Showing which communication skills and risk presentations affect
      client's feelings and decisions may help to improve genetic counseling.

PMID- 16406475
TI  - The effects of smoking cessation counseling by midwives on Dutch pregnant women
      and their partners.
AB  - OBJECTIVE: Smoking during pregnancy is an important problem in the Netherlands.
      We tested the effectiveness of a health counseling method by midwives using a
      RCT. METHODS: Four provinces with 42 practices including 118 midwives were
      randomly assigned to the experimental or control condition. Midwives in the
      experimental group provided brief health counseling, self-help materials on
      smoking cessation during pregnancy and early postpartum, and a partner booklet.
      Controls received routine care. The main outcome measures were 7-day abstinence,
      continuous abstinence, and partner smoking at 6 weeks post-intervention (T1) and
      6 weeks postpartum (T2). RESULTS: Multi-level analysis revealed significant
      differences between both conditions at T1 and T2 using intention-to-treat
      analysis. Nineteen percent of the experimental group reported 7-day abstinence
      compared to 7% of the control group at T1, and 21 and 12%, respectively, at T2.
      For continuous abstinence these percentages were 12% in the experimental group
      and 3% in the control group. The partner intervention was not successful.
      CONCLUSION: The intervention resulted in significant effects on smoking behavior
      for pregnant women, but not for partner smoking. PRACTICE IMPLICATIONS: The
      program realized short-term effects. An important precondition is that midwives
      need a proper training.

PMID- 16406476
TI  - Cell culture models for the investigation of NRTI-induced mitochondrial toxicity.
      Relevance for the prediction of clinical toxicity.
AB  - The introduction of highly active antiretroviral therapy (HAART) for treatment of
      human immunodeficiency virus (HIV) infection has led to substantial reduction in
      morbidity and near-complete suppression of HIV-1 replication. But since HAART is
      unlikely to eradicate HIV-1, antiviral therapy may be required a lifelong,
      leading to an increase in attention on the long-term safety of HAART. A major
      toxicity of HAART is the mitochondrial toxicity. Mitochondrial toxicity becomes
      apparent particularly over the medium-term to long-term therapy and is attributed
      to treatment with nucleoside reverse transcriptase inhibitors (NRTIs), leading to
      a wide range of severe adverse events in HIV-infected patients. These include
      lactic acidosis, hepatic steatosis, neuropathy, (cardio-) myopathy, pancreatitis,
      and probably lipodystrophy. Furthermore, lactic acidosis and encephalopathy have
      been reported in children exposed in-utero and/or postnatally to NRTIs.
      Mitochondrial toxicity could pose a major threat to long-term success of HIV
      therapy, and is of great concern for children exposed in-utero and/or postnatally
      to NRTIs. Therefore, investigation of mitochondrial toxicity of new compounds or
      new combinations is of growing interest for the clinical application of
      antiretroviral agents. However, at present no standardized and validated
      screening model system exists for the investigation of NRTI-induced mitochondrial
      toxicity. There is a need for the generation of a relevant in vitro assay system
      that can assess the mitochondrial toxicity in early preclinical development. This
      paper gives an overview of cell culture models currently used for the
      investigation of NRTI-induced mitochondrial toxicity and discusses the relevance
      and suitability of these models for prediction of clinical toxicity.

PMID- 16406477
TI  - Anaerobic treatment of phenol in wastewater under thermophilic condition.
AB  - Over 99% of phenol was effectively degraded in an upflow anaerobic sludge blanket
      (UASB) reactor at 55 degrees C with 40 h of hydraulic retention time (HRT) for a
      wastewater containing 630 mg/L of phenol, corresponding to 1500 mg/L of chemical
      oxygen demand (COD) and a loading rate of 0.9 g-COD/L/d. The maximum specific
      methanogenic activity (SMA) of the phenol-degrading sludge was 0.09 g-CH4-COD/g
      volatile suspended solids (VSS)/d. Based on 16S rDNA analysis, a total of 21
      operational taxonomy units (OTUs) were found in the sludge, of which eight (42.6%
      of the total population) were related to the sequences in the GenBank with
      similarity of over 97%, and 13 (79.6%) were affiliated with the known
      thermophilic species. Additional SMA data and phylogenetic analysis suggest that
      the degradation pathway of phenol for thermophilic sludge was likely via
      caproate, instead of benzoate as for the mesophilic sludge.

PMID- 16406478
TI  - Arsenic removal from an aqueous solution by a modified fungal biomass.
AB  - Non-viable fungal biomass of Aspergillus niger, coated with iron oxide was
      investigated for its potential to remove arsenic from an aqueous solution. A.
      niger biomass coated with iron oxide showed maximum removal (approximately 95% of
      As(V) and 75% of As(III)) at a pH of 6. No strong relationship was observed
      between the surface charge of the biomass and arsenic removal.

PMID- 16406480
TI  - Antidepressant drugs during pregnancy and infant congenital heart defect.

PMID- 16406479
TI  - Mancozeb adversely affects meiotic spindle organization and fertilization in
      mouse oocytes.
AB  - In this study the effects of mancozeb, a widely used ethylenebisdithiocarbamate
      fungicide, on mouse oocyte meiotic maturation and fertilization were analyzed.
      Oocyte cumulus cell-complexes were matured in vitro with or without increasing
      concentrations of the fungicide (from 0.001 to 1 microg/ml) that, due to its
      different stability in organic solvents and in water, was resuspended either in
      dimethyl sulfoxide or in culture medium. Although, about 95% of oocytes reached
      the metaphase II stage; mancozeb-exposed oocytes showed a dose-dependent increase
      of alterations in spindle morphology, and this negative effect was more evident
      when the fungicide was resuspended in culture medium. Under the latter culture
      condition, oocytes matured in the presence of 0.1 and 1 microg/ml mancozeb showed
      a significant reduction also in the formation of male and female pronuclei. These
      results indicate that mancozeb can adversely affect mammalian reproductive
      performance, likely by perturbing microtubular organization during meiotic
      maturation.

PMID- 16406481
TI  - Social paper wasps as bioindicators: a preliminary research with Polistes
      dominulus (Hymenoptera Vespidae) as a trace metal accumulator.
AB  - The wasps of the genus Polistes (paper wasps), have a worldwide distribution and
      are widespread in human-built areas. Like other social wasps, they are at the top
      of food chains and are therefore exposed to the dangers of biomagnification,
      given that the larvae are fed predominantly with prey that consist of herbivorous
      insects. The larval faeces, larval fecal masses, in the form of a semi-solid
      ball, are made up of the residues of the diet of the larva, which are emitted and
      compressed on the floor of the cell during the larval metamorphosis. Larval fecal
      masses may accumulate lead (up to 36 times with respect to the adult body),
      therefore they were used as substrate for the analysis. From the analysis of
      sample nests of Polistes dominulus in various sites of the urban area of
      Florence, it emerges that the larval fecal masses are an analytical substrate
      with which it is possible to distinguish zones with differing degrees of lead
      pollution. The lead concentration measured in the larval fecal masses turns out
      to be directly correlated with vehicle traffic density, the main lead source in
      Florence when the survey was carried out. The notable increase in the lead
      concentration of larval fecal masses from the rural to the urban nest (11.15
      times), in contrast with the much more limited level of pupae (4.39 times), seems
      to indicate the efficiency of the excretion and/or barrier mechanisms. These
      wasps seem to be a promising species for biomonitoring lead pollution in order to
      better understand its dynamics in anthropic ecosystems after the progressive
      diffusion of unleaded gasoline.

PMID- 16406482
TI  - Chemical characterizations of soluble aerosols in southern China.
AB  - Soluble aerosols are measured at Guangdong and Hainan Provinces of southern
      China. The measured chemical composition of aerosols includes F-, Cl-, NO3-,
      SO4=, Na+, NH4+, K+, Ca2+, and Mg2+. The locations of measurements include a mega
      city (Guangzhou), a medium city along the coastline (Haiko), a small city along
      the coastline (Shanya), and a remote island site in the South China Sea (Yongxing
      island). The results reveal that aerosols in this region are complex and
      heterogeneous. Sulfate aerosol (SO4=) has the highest concentrations in Guangzhou
      (approximately 41% of total soluble aerosol mass), suggesting that anthropogenic
      activities (e.g., coal burning) play important roles in controlling aerosol
      concentrations in Guangzhou. By contrast, the concentrations of chlorine (Cl-)
      and sodium (Na+) are higher in Yongxing than in Guangzhou, indicating that the
      sea salt is the dominant aerosol in this marine environment site. In the medium
      (Haiko) and small (Shanya) city sites, the effects of anthropogenic and marine
      activities on aerosols fall in between the values in the mega city and the remote
      island site. The measured ratio of Cl-/Na+ shows that the ratio is less than 1.16
      in all observation sites. The ratio in the Guangzhou city, the Haiko city, the
      Shanya city, and the Yongxing island is 0.52, 0.91, 0.24, and 0.53, respectively,
      indicating that significantly heterogeneous chemical reactions occur on sea salt
      particles. Unlike those in Europe and North America, there are high
      concentrations of calcium (Ca+) in all observation sites. The percentage of
      calcium mass to the measured total soluble aerosols mass is 21, 32, 34, and 30 at
      Guangzhou, Haiko, Sanya, and Yongxing, respectively. The calculations show that
      calcium plays an important role in neutralizing aerosols. The calculated
      "cation/anion" (summation operator[ion+]/summation operator[ion-]) ratio is 2.5,
      2.5, 3.2, and 2.1, at Guangzhou, Haiko, Shanya, and Yongxing, respectively. The
      high "cation/anion" ratios suggest that SO4=, NO3-, and Cl- are neutralized, and
      the aerosols as a whole (internally mixed), appear to be in an alkaline mode in
      this region. However, without taking into account for calcium, the calculated
      "cation/anion" ratio reduces to 1.2, 0.98, 1.3, and 0.8 at Guangzhou, Haiko,
      Sanya, and Yongxing, respectively. The property of aerosols switches from an
      alkaline mode to an acidity mode at the Haiko and Yongxing sites.

PMID- 16406483
TI  - A study of polycyclic aromatic hydrocarbons concentrations and source
      identifications by methods of diagnostic ratio and principal component analysis
      at Taichung chemical Harbor near Taiwan Strait.
AB  - Fine (PM(2.5)) and Coarse (PM(2.5-10)) particulates concentrations of ambient air
      particle-bound polycyclic aromatic hydrocarbons (PAHs) were measured
      simultaneously from February 2004 to January 2005 at the Taichung Harbor (TH)
      sampling site near Taiwan of central Taiwan. Particle-bound polycyclic aromatic
      hydrocarbons (PAHs) were collected on quartz filters, the collected sample used
      soxhlet analytical method extracted with a dichloromethane (DCM)/n-hexane mixture
      (50/50, v/v) for 24h, and then the extracts were subjected to gas chromatography
      mass spectrometric (GC-MS) analysis. The results indicated that vehicle
      emissions, coal combustion, incomplete combustion and pyrolysis of fuel and oil
      burning were the main source of PAHs near Taiwan Strait of central Taiwan.
      Diagnostic ratio and principal component analysis (PCA) were also used to
      characterize and identify PAHs emission source in this study.

PMID- 16406485
TI  - Dependence of photocatalytic activity of anatase powders on their crystallinity.
AB  - Structural changes in anatase phase in four TiO(2) photocatalysts with annealing
      at high temperatures were followed by evaluating crystallite size and lattice
      strain of anatase phase separately and measuring the content of anatase. The rate
      constant k for the decomposition of methylene blue in its aqueous solution under
      UV irradiation was determined as a measure of photocatalytic activity. Marked
      dependences in crystallinity improvement, i.e., the growth of crystallite and the
      decrease in lattice strain, and in phase transformation from anatase to rutile
      phases of TiO(2) on annealing temperature was observed above 500 degrees C,
      depending on starting photocatalysts used. The phase transformation to rutile
      started after reaching of crystallite size to about 32 nm and of lattice strain
      to about 0.5 x 10(-3). Rate constant k was found to depend on both crystallite
      size and lattice strain of anatase; it increased with increasing crystallite size
      up to about 32 nm and decreasing lattice strain down to about 0.5 x 10(-3).
      Further increase in crystallite size and decrease in lattice strain induced the
      decrease in rate constant k, mainly due to the partial transformation of anatase
      to rutile. The present results showed that the activity of the photocatalysts was
      possible to be improved by annealing at a high temperature, by selecting an
      optimal condition of annealing for getting a high crystallinity in anatase phase
      and no phase transformation to rutile phase.

PMID- 16406484
TI  - Biodegradation of polychlorinated biphenyls using biofilm grown with biphenyl as
      carbon source in fluidized bed reactor.
AB  - This study investigated the use of biofilms in the biodegradation of
      polychlorinated biphenyls. The biofilm used was developed on modified cement
      particles using mixed microbial culture isolated from PCB-contaminated soil. The
      biofilm formed was first acclimatized to PCBs by feeding the reactor alternately
      with biphenyl and PCBs. The acclimatized biofilm was tested on simulated PCB
      contaminated water containing Aroclor 1260 by using a three-phase fluidized-bed
      reactor operated in batch mode. The initial batch run yielded 80+/-2.38% PCB
      removal from medium in one day and 91+/-1.34% in 5 days. The percent PCB removal
      gradually increased in the succeeding runs reaching 92+/-2.48% in one day and a
      steady state value of 95+/-2.01% in 5 days from batch eight onwards. PCB removal
      from the medium was highest during the first day reaching 80-92%. The sudden
      decrease in PCB concentration was attributed to an initial adsorption of the PCB
      on the biofilm and then the compound was degraded gradually. Yellow intermediates
      were observed as the pH of the medium decreased. These intermediate products were
      further metabolized as indicated by the disappearance of the yellow substance.

PMID- 16406486
TI  - Determination of sterols, estrogens and inorganic ions in waste water and size
      segregated aerosol particles emitted from waste water treatment.
AB  - Concentrations of steroids and inorganic ions were measured in waste water of an
      aerated sand trap as well as in aerosol particles emitted from this tank at the
      waste water treatment plant (WWTP) of Bayreuth, Germany, in January and February
      2003. The investigations comprised seven sterols, two estrogens, and several
      inorganic ions. Since an appropriate method for the determination of sterols in
      waste water was not available, a new method based on solid phase extraction was
      developed. The concentrations of the sterols coprostanol and cholesterol amounted
      to 30-180 microg l(-1) in waste water and to 400-5000 pg m(-3) in aerosol
      particles. All other sterols were present in markedly lower concentrations. The
      mean concentrations of the two estrogens estrone and 17beta-estradiol were about
      165 pg m(-3) in aerosol particles. The steroid concentrations in both waste water
      and aerosol particles varied greatly over time, however with the exception of
      coprostanol, no clear correlation was detected between concentrations in waste
      water and aerosol particles.

PMID- 16406487
TI  - Soil remediation time to achieve clean-up goals II: Influence of natural organic
      matter and water contents.
AB  - This work reports a relatively rapid procedure for the forecasting of the
      remediation time (RT) of sandy soils contaminated with cyclohexane using vapour
      extraction. The RT estimated through the mathematical fitting of experimental
      results was compared with that of real soils. The main objectives were: (i) to
      predict the RT of soils with natural organic matter (NOM) and water contents
      different from those used in experiments; and (ii) to analyse the time and
      efficiency of remediation, and the distribution of contaminants into the soil
      matrix after the remediation process, according to the soil contents of: (ii1)
      NOM; and (ii2) water. For sandy soils with negligible clay contents, artificially
      contaminated with cyclohexane before vapour extraction, it was concluded that:
      (i) if the NOM and water contents belonged to the range of the prepared soils,
      the RT of real soils could be predicted with relative differences not higher than
      12%; (ii1) the increase of NOM content from 0% to 7.5% increased the RT (1.8-13
      h) and decreased the remediation efficiency (RE) (99-90%) and (ii2) the increase
      of soil water content from 0% to 6% increased the RT (1.8-4.9 h) and decreased
      the RE (99-97%). NOM increases the monolayer capacity leading to a higher
      sorption into the solid phase. Increasing of soil water content reduces the mass
      transfer coefficient between phases. Concluding, NOM and water contents influence
      negatively the remediation process, turning it less efficient and more time
      consuming, and consequently more expensive.

PMID- 16406489
TI  - A sensitive radioimmunoassay of insulin autoantibody: reduction of non-specific
      binding of [125I]insulin.
AB  - There has been a lack of consensus among results of assays for insulin
      autoantibody (IAA) carried out by different laboratories, despite a reduction in
      the non-specific effect using a cold insulin competitor in radioimmunoassays
      (RIAs) for IAA in type I diabetes. We speculated that the discrepancies are
      partly a result of the non-specific binding (NSB) of [125I]insulin to
      unidentified molecules in serum on polyethylene glycol separation, and tried to
      improve IAA RIAs. The molecular weight of a candidate for the factor causing NSB
      was estimated to be about 700 kDa by gel filtration analysis, resembling that of
      alpha 2-macroglobulin (a2M). Further, the addition of purified a2M to the assay
      resulted in an increase in NSB. Screening revealed that heterocyclic compounds,
      such as isothiazolinone derivatives (ProClin300), were greatly effective at
      reducing NSB in control subjects from 2.904+/-0.909% to 1.347+/-0.254% (n=283,
      mean+/-SD, p<0.0001). Using our newly developed IAA RIA with ProClin300, the
      sensitivity for newly diagnosed type I diabetes patients (n=55) was 32.7% and
      30.9% with or without insulin competition, respectively, whereas that of the
      former assay without ProClin300 was only 20.0%.

PMID- 16406488
TI  - Involvement of nitric oxide pathway in the acute anticonvulsant effect of
      melatonin in mice.
AB  - Melatonin, the major hormone produced by the pineal gland, is shown to have
      anticonvulsant effects. Nitric oxide (NO) is a known mediator in seizure
      susceptibility modulation. In the present study, the involvement of NO pathway in
      the anticonvulsant effect of melatonin in pentylenetetrazole (PTZ)-induced clonic
      seizures was investigated in mice. Acute intraperitoneal administration of
      melatonin (40 and 80 mg/kg) significantly increased the clonic seizure threshold
      induced by intravenous administration of PTZ. This effect was observed as soon as
      1 min after injection and lasted for 30 min with a peak effect at 3 min after
      melatonin administration. Combination of per se non-effective doses of melatonin
      (10 and 20 mg/kg) and nitric oxide synthase (NOS) substrate L-arginine (30, 60
      mg/kg) showed a significant anticonvulsant activity. This effect was reversed by
      NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg), implying an
      NO-dependent mechanism for melatonin effect. Pretreatment with L-NAME (30 mg/kg)
      and N(G)-nitro-L-arginine (L-NNA, 10 mg/kg) inhibited the anticonvulsant property
      of melatonin (40 and 80 mg/kg) and melatonin 40 mg/kg, respectively. Specific
      inducible NOS (iNOS) inhibitor aminoguanidine (100 and 300 mg/kg) did not affect
      the anticonvulsant effect of melatonin, excluding the role of iNOS in this
      phenomenon, while pretreatment of with 7-NI (50 mg/kg), a preferential neuronal
      NOS inhibitor, reversed this effect. The present data show an anticonvulsant
      effect for melatonin in i.v. PTZ seizure paradigm, which may be mediated via NO/L
      arginine pathway by constitutively expressed NOS.

PMID- 16406490
TI  - Environmental contaminants and biomarker responses in fish from the Columbia
      River and its tributaries: spatial and temporal trends.
AB  - Fish were collected from 16 sites on rivers in the Columbia River Basin (CRB)
      from September 1997 to April 1998 to document temporal and spatial trends in the
      concentrations of accumulative contaminants and to assess contaminant effects on
      the fish. Sites were located on the mainstem of the Columbia River and on the
      Snake, Willamette, Yakima, Salmon, and Flathead Rivers. Common carp (Cyprinus
      carpio), black bass (Micropterus sp.), and largescale sucker (Catostomus
      macrocheilus) were the targeted species. Fish were field-examined for external
      and internal lesions, selected organs were weighed to compute somatic indices,
      and tissue and fluid samples were preserved for fish health and reproductive
      biomarker analyses. Composite samples of whole fish, grouped by species and
      gender, from each site were analyzed for organochlorine and elemental
      contaminants using instrumental methods and for 2,3,7,8-tetrachloro dibenzo-p
      dioxin-like activity (TCDD-EQ) using the H4IIE rat hepatoma cell bioassay.
      Overall, pesticide concentrations were greatest in fish from lower CRB sites and
      elemental concentrations were greatest in fish from upper CRB sites. These
      patterns reflected land uses. Lead (Pb) concentrations in fish from the Columbia
      River at Northport and Grand Coulee, Washington (WA) exceeded fish and wildlife
      toxicity thresholds (>0.4 microg/g). Selenium (Se) concentrations in fish from
      the Salmon River at Riggins, Idaho (ID), the Columbia River at Vernita Bridge,
      WA, and the Yakima River at Granger, WA exceeded toxicity thresholds for
      piscivorous wildlife (>0.6 microg/g). Mercury (Hg) concentrations in fish were
      elevated throughout the basin but were greatest (>0.4 microg/g) in predatory fish
      from the Salmon River at Riggins, ID, the Yakima River at Granger, WA, and the
      Columbia River at Warrendale, Oregon (OR). Residues of p,p'-DDE were greatest
      (>0.8 microg/g) in fish from agricultural areas of the Snake, Yakima, and
      Columbia River basins but were not detected in upper CRB fish. Other
      organochlorine pesticides did not exceed toxicity thresholds in fish or were
      detected infrequently. Total polychlorinated biphenyls (PCBs; >0.11 microg/g) and
      TCDD-EQs (>5 pg/g) exceeded wildlife guidelines in fish from the middle and lower
      CRB, and ethoxyresorufin O-deethylase (EROD) activity was also elevated at many
      of the same sites. Temporal trend analysis indicated decreasing or stable
      concentrations of Pb, Se, Hg, p,p'-DDE, and PCBs at most sites where historical
      data were available. Altered biomarkers were noted in fish throughout the CRB.
      Fish from some stations had responded to chronic contaminant exposure as
      indicated by fish health and reproductive biomarker results. Although most fish
      from some sites had grossly visible external or internal lesions,
      histopathological analysis determined these to be inflammatory responses
      associated with helminth or myxosporidian parasites. Many largescale sucker from
      the Columbia River at Northport and Grand Coulee, WA had external lesions and
      enlarged spleens, which were likely associated with infections. Intersex male
      smallmouth bass (Micropterus dolomieu) were found in the Snake River at Lewiston,
      ID and the Columbia River at Warrendale, OR. Male bass, carp, and largescale
      sucker containing low concentrations of vitellogenin were common in the CRB, and
      comparatively high concentrations (>0.3 mg/mL) were measured in male fish from
      the Flathead River at Creston, Montana, the Snake River at Ice Harbor Dam, WA,
      and the Columbia River at Vernita Bridge, WA and Warrendale, OR. Results from our
      study and other investigations indicate that continued monitoring in the CRB is
      warranted to identify consistently degraded sites and those with emerging
      problems.

PMID- 16406491
TI  - Mercury distribution in two Sierran forest and one desert sagebrush steppe
      ecosystems and the effects of fire.
AB  - Mercury (Hg) concentration, reservoir mass, and Hg reservoir size were determined
      for vegetation components, litter, and mineral soil for two Sierran forest sites
      and one desert sagebrush steppe site. Mercury was found to be held primarily in
      the mineral soil (maximum depth of 60 to 100 cm), which contained more than 90%
      of the total ecosystem reservoir. However, Hg in foliage, bark, and litter plays
      a more dominant role in Hg cycling than the mineral soil. Mercury partitioning
      into ecosystem components at the Sierran forest sites was similar to that
      observed for other US forest sites. Vegetation and litter Hg reservoirs were
      significantly smaller in the sagebrush steppe system because of lower biomass.
      Data collected from these ecosystems after wildfire and prescribed burns showed a
      significant decrease in the Hg pool from certain reservoirs. No loss from mineral
      soil was observed for the study areas but data from fire severity points
      suggested that Hg in the upper few millimeters of surface soil may be volatilized
      due to exposure to elevated temperatures. Comparison of data from burned and
      unburned plots suggested that the only significant source of atmospheric Hg from
      the prescribed burn was combustion of litter. Differences in unburned versus
      burned Hg reservoirs at the forest wildfire site demonstrated that drastic
      reduction in the litter and above ground live biomass Hg reservoirs after burning
      had occurred. Sagebrush and litter were absent in the burned plots after a
      wildfire suggesting that both reservoirs were released during the fire. Mercury
      emissions due to fire from the forest prescribed burn, forest wildfire, and
      sagebrush steppe wildfire sites were roughly estimated at 2.0 to 5.1, 2.2 to 4.9,
      and 0.36+/-0.13 g ha(-1), respectively, with litter and vegetation being the most
      important sources.

PMID- 16406492
TI  - Functional characterization of the calcipressin 1 motif that suppresses
      calcineurin-mediated NFAT-dependent cytokine gene expression in human T cells.
AB  - Inhibition of the calcineurin-NFAT signalling pathway is one of the main
      challenges for immunosuppression therapy to avoid the severe side effects of the
      current anticalcineurinic drugs, cyclosporin A and FK506. The members of the
      calcipressin family are endogenous inhibitors of calcineurin. We describe for the
      first time that two independent motifs within human calcipressin 1, the ELHA and
      the PxIxxT motifs, interact with calcineurin in an independent functional manner.
      However, the main finding here is that the ELHA-containing calcineurin-inhibitor
      CALP1 (CIC) motif is the responsible for the in vivo inhibition of calcineurin
      mediated NFAT-dependent cytokine gene expression in human T cells. We believe
      that the identification of the CIC motif could be used as a starting point for
      the development of new immunosuppressive drugs for use in transplantation and
      autoimmune diseases.

PMID- 16406493
TI  - Dynamic dissolution of persimmon leaves in DMSO and DMAc and the influence of
      acid-base interactions.
AB  - Applying conductivity as a measure, dynamic behavior for dissolution of persimmon
      leaves in two organic solvents, e.g. DMSO and DMAc, respectively, were recorded
      and a mathematical model described as: dC/dt = k0 + k1C + k2C2 was deduced (of
      which, C is the concentration dissolved, k0, k1 and k2 are the different
      dissolution rate constants corresponding different dissolution stages and t is
      the time). Results showed that the DMAc seems to be better than that of DMSO due
      probably to the former having a higher activation energy and smaller acid/base
      ratio and polarity comparing to the latter. However, for a lower temperature, it
      seems to be contrary due to DMSO presented greater dissolution rate constant than
      that of DMAc.

PMID- 16406494
TI  - Imaging of a soft, weakly adsorbing, living cell with a colloid probe tapping
      atomic force microscope technique.
AB  - Here, we propose a new method to improve the atomic force microscopy (AFM) image
      resolution of soft samples, such as cells, in liquid. Attaching a colloid probe
      to a cantilever was seen improve the image resolution of a living cell in a
      physiological buffer solution, obtained by the normal tapping mode, when compared
      to an image obtained using a regular cantilever tip. This may be due to the
      averaging out of the cantilever tip swinging caused by the visco-elasticity of
      the cell. The resolution was best, when silica spheres with a 3.3 microm diameter
      were attached. Although larger spheres gave a resolution better than a bare
      cantilever tip, their resolution was less than that obtained for the 3.3 microm
      diameter silica colloid. This dependency of the image resolution on the colloid
      probe size may be a result of the increased macroscopic van der Waals attraction
      between the cell and probe, the decreased repulsive force dependence on the
      cantilever probe radius, and the decrease in resolution due to the increased
      probe size. The size of the colloid probe, which should be attached to the
      cantilever to give the best image resolution, would be the one that optimises the
      combined result of these facts.

PMID- 16406495
TI  - Assessment of insight into delusional beliefs in schizophrenia using the Brown
      Assessment of Beliefs Scale.

PMID- 16406496
TI  - Cell cycle alterations in biopsied olfactory neuroepithelium in schizophrenia and
      bipolar I disorder using cell culture and gene expression analyses.
AB  - We previously demonstrated that olfactory cultures from individuals with
      schizophrenia had increased cell proliferation compared to cultures from healthy
      controls. The aims of this study were to (a) replicate this observation in a new
      group of individuals with schizophrenia, (b) examine the specificity of these
      findings by including individuals with bipolar I disorder and (c) explore gene
      expression differences that may underlie cell cycle differences in these
      diseases. Compared to controls (n = 10), there was significantly more mitosis in
      schizophrenia patient cultures (n = 8) and significantly more cell death in the
      bipolar I disorder patient cultures (n = 8). Microarray data showed alterations
      to the cell cycle and phosphatidylinositol signalling pathways in schizophrenia
      and bipolar I disorder, respectively. Whilst caution is required in the
      interpretation of the array results, the study provides evidence indicating that
      cell proliferation and cell death in olfactory neuroepithelial cultures is
      differentially altered in schizophrenia and bipolar disorder.

PMID- 16406497
TI  - [Snoring in children].
AB  - Only snoring loud enough to be heard behind a closed door have to be investigated
      and treated. Snoring is severe when associated with sleep apneas. The 3 most
      frequent causes of snoring in children are enlarged adenoids, enlarged tonsils
      and blocked nose due to allergic rhinitis.

PMID- 16406498
TI  - Fibrinogen Guarenas, an abnormal fibrinogen with an Aalpha-chain truncation due
      to a nonsense mutation at Aalpha 467 Glu (GAA)-->stop (TAA).
AB  - Fibrinogen Guarenas is a dysfibrinogenemia with a nonsense mutation at G4731T
      that causes an Aalpha-chain truncation at Ser 466. This abnormal fibrinogen is
      associated with a bleeding diathesis, severe in the proposita and mild in one
      brother, even though the fibrinogen levels in plasma are normal. All other family
      members are asymptomatic. Fibrinogens from the proposita and one family member,
      the mother of the proposita, both heterozygous for the mutation, were studied.
      Turbidity curves of fibrin polymerization showed that the lateral association of
      protofibrils was impaired and the maximum rate of polymerization was slightly
      diminished. The binding of albumin to fibrinogen was increased compared to
      control due to the presence of a free sulfhydryl group because of the missing
      disulphide bridge between Aalpha-Cys 442-472 in the mutated molecules. The
      abnormal fibrinogen formed much less alpha-polymer, and gamma-dimer formation was
      delayed compared to the control. Plasminogen activation by t-PA in the presence
      of fibrin was decreased. When Guarenas clots were perfused with fibrinolytic
      enzymes, clot degradation was retarded. Clot structure studied by confocal 3D
      microscopy showed that the fibrin network was dense, made up of thin and highly
      branched fibers, which accounted for the decreased flow rates by buffer
      permeation and increased rigidity of the fibrin clots, measured using a torsion
      pendulum. It seems that the increased clot rigidity, decreased porosity,
      hypofibrinolysis and t-PA induced fibrinolysis, by itself are not necessarily
      associated with thrombotic disorders in dysfibrinogenemia.

PMID- 16406499
TI  - Selection of a battery of rapid toxicity sensors for drinking water evaluation.
AB  - Comprehensive identification of chemical contaminants in Army field water
      supplies can be a lengthy process, but rapid analytical methods suitable for
      field use are limited. A complementary approach is to directly measure toxicity
      instead of individual chemical constituents. Ten toxicity sensors utilizing
      enzymes, bacteria, or vertebrate cells were tested to determine the minimum
      number of sensors that could rapidly identify toxicity in water samples
      containing one of 12 industrial chemicals. The ideal sensor would respond at a
      concentration just exceeding the Military Exposure Guideline (MEG) level for the
      chemical (an estimated threshold for adverse effects) but below the human lethal
      concentration. Chemical solutions were provided to testing laboratories as blind
      samples. No sensors responded to deionized water blanks, and only one sensor
      responded to a hard water blank. No single toxicity sensor responded to more than
      six chemicals in the desired response range, and one chemical (nicotine) was not
      detected by any sensor with the desired sensitivity. A combination of three
      sensors (Microtox, the Electric Cell Substrate Impedance Sensing (ECIS) test, and
      the Hepatocyte low density lipoprotein (LDL) uptake test) responded appropriately
      to nine of twelve chemicals. Adding a fourth sensor (neuronal microelectrode
      array) to the test battery allowed detection of two additional chemicals
      (aldicarb and methamidophos), but the neuronal microelectrode array was overly
      sensitive to paraquat. Evaluating sensor performance using a standard set of
      chemicals and a desired sensitivity range provides a basis both for selecting
      among available toxicity sensors and for evaluating emerging sensor technologies.
      Recommendations for future toxicity sensor evaluations are discussed.

PMID- 16406500
TI  - Amperometric immunosensor for nonylphenol determination based on peroxidase
      indicating reaction.
AB  - Novel immunosensor for nonylphenol (NP) determination has been developed by
      immobilization of specific antibodies together with horseradish peroxidase on the
      surface of carbon screen-printed electrode. The signal of the immunosensor is
      generated by the involvement of NP accumulated in the peroxidase oxidation of
      mediator (Methylene Blue, hydroquinone or iodide). This results in the increase
      of the signal recorded by linear-sweep voltammetry. The sensitivity of the
      detection depends on the nature of mediator, its concentration and incubation
      period. Cross-selectivity of the response toward readily oxidized phenolic
      compounds has been determined. The immunosensor developed makes it possible to
      detect from 20 microgL(-1) to 44 mgL(-1) of NP with detection limit 10 microgL(
      1) of NP.

PMID- 16406501
TI  - Expression of PKC isoforms in human melanocytic cells in situ.

PMID- 16406502
TI  - Evaluation of gender difference in skin type and pH.

PMID- 16406503
TI  - Cavum septum pellucidum and adhesio interthalamica in schizophrenia: an MRI
      study.
AB  - Several studies have independently suggested that patients with schizophrenia are
      more likely to have an enlarged cavum septum pellucidum (CSP) and an absent
      adhesio interthalamica (AI), respectively. However, neither finding has been
      consistently replicated and it is unclear whether there is an association between
      these two midline brain abnormalities. Thus, we compared the prevalence of absent
      AI and the prevalence, size and volume of CSP in 38 patients with schizophrenia
      and 38 healthy controls using magnetic resonance imaging (MRI). There were no
      between group differences in the presence or volume of CSP; however, an enlarged
      CSP was commoner among patients than controls. There was also a positive
      correlation between CSP ratings and volumes. No differences in the presence or
      absence of the AI were found between patients and controls; however, an absent AI
      was commoner in male patients with schizophrenia than females. There was
      absolutely no overlap between the presence of a large CSP and an absence of AI.
      In conclusion, our findings are in line with several case series and other MRI
      investigations that have shown a higher incidence of putatively developmental
      brain abnormalities in patients with schizophrenia, particularly in males, and
      support the neurodevelopmental model of this disorder.

PMID- 16406504
TI  - Outcomes for patients with T1 squamous cell cancer of the vulva undergoing
      sentinel node biopsy.
AB  - OBJECTIVE: This retrospective review was undertaken to evaluate survival in
      patients with T1 squamous cell carcinoma of the vulva treated with radical local
      excision and sentinel node dissection. METHODS: Patients with T1 cancers
      underwent pre-operative lymphoscintigraphy and sentinel lymph node dissection
      using technetium sulfur colloid and isosulfan blue dye. The primary tumor was
      removed with radical local excision. Patients with negative sentinel nodes did
      not receive any additional treatment. Survival was calculated using life table
      analysis. RESULTS: There were 21 patients who underwent 27 sentinel node
      dissections. Three patients were found to have positive sentinel nodes. At a
      median follow-up of 4.6 years, two patients have died of cancer, and three
      patients have died of intercurrent illness. None of the patients with negative
      sentinel nodes has died of cancer. There were no groin or distant recurrences in
      patients with negative sentinel nodes. Three-year disease-free survival for all
      patients and for patients with negative sentinel nodes were 90% and 100%
      respectively. CONCLUSION: The survival for patients with early vulvar cancer
      treated with sentinel node dissection and radical local excision appears
      excellent.

PMID- 16406505
TI  - GLI transcription factors: mediators of oncogenic Hedgehog signalling.
AB  - The current concept of tumourigenesis holds that cancer results from the
      progressive acquisition of mutations that endow affected cells with selective
      growth advantages by activating multiple processes including intrinsic mitogenic
      and pro-survival pathways. Constitutive activation of the Hedgehog (HH)/GLI
      signalling cascade has recently been implicated in the growth of a number of
      human malignancies ranging from semi-malignant tumours of the skin to highly
      aggressive cancers of the brain, lung, pancreas and prostate. This review focuses
      on the role of the GLI zinc finger transcription factors, which mediate Hedgehog
      signalling at the distal end of the pathway. We summarise recent data on the
      mechanisms by which latent GLI proteins are activated in response to stimulation
      of Hedgehog signalling. Based on the identification of a growing number of direct
      GLI target genes, we propose that HH-driven tumourigenesis relies on multiple
      cellular processes such as promotion of G1/S phase progression, enhancement of
      cell survival by providing anti-apoptotic cues, increase in metastatic potential
      of Hedgehog responsive cells, and activation of potential tumour stem cells. In
      view of the critical role of GLI genes in Hedgehog-associated cancers, strategies
      that aim at interfering with GLI function are likely to represent efficient
      approaches in future targeted cancer therapy.

PMID- 16406506
TI  - Mechanisms of pericyte recruitment in tumour angiogenesis: a new role for
      metalloproteinases.
AB  - Pericytes occur in tumour blood vessels and are critical for the development of a
      functional vascular network. Targeting tumour pericytes is a promising anti
      angiogenic therapy but requires identifying the mechanisms of their recruitment
      in tumour and addressing whether these mechanisms can be selectively harnessed.
      Among the pathways involved in pericyte recruitment during embryonic development,
      the contribution of platelet-derived growth factor B and sphingosine 1-phosphate
      is confirmed in tumour angiogenesis. The effect of angiopoietin 1 depends on the
      tumour model. Transforming growth factor-beta1 enhances tumour vascularization
      and microvessel maturation. Recent reports suggest a participation of matrix
      metalloproteinases (MMP) in tumour pericyte recruitment that is consistent with
      the effect of certain MMPs in the development of microvasculature in embryonic
      development and in in vitro models of vascular remodelling. Here, we discuss the
      possibility for MMPs to contribute to pericyte recruitment at six levels: (1)
      direct promotion of pericyte invasion by extracellular matrix degradation; (2)
      stimulation of pericyte proliferation and protection against apoptosis by
      modification of the ECM; (3) activation of pericytes through the release of
      growth factor bound to the ECM; (4) transactivation of angiogenic cell surface
      receptor; (5) propagation of angiogenic signalling as cofactor; and (6)
      recruitment of bone marrow-derived stem cells.

PMID- 16406507
TI  - Phase I study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with
      5-fluorouracil and leucovorin: a safe combination.
AB  - We performed a phase I study with the thrombospondin-1-mimetic angiogenesis
      inhibitor ABT-510 combined with 5-fluorouracil and leucovorin (5-FU/LV) to
      determine safety profile and assess pharmacokinetic interactions. Patients with
      advanced solid malignancies received LV 20 mg/m(2) followed by 5-FU 425 mg/m(2)
      both administered intravenously in 15 min daily for 5 days every 4 weeks. ABT-510
      was administered subcutaneously twice daily continuously from day 2 onwards.
      Blood and urine samples for pharmacokinetic analyses were collected at days 1, 5
      and 22. Twelve patients received a total of 45 cycles of 5-FU/LV combined with
      ABT-510. ABT-510 dose levels studied were 50 and 100 mg. The combination was well
      tolerated, with a toxicity profile comparable to that of 5-FU/LV alone. At the
      dose levels studied no significant pharmacokinetic interactions were observed.
      These data indicate that ABT-510 administered twice daily subcutaneously can be
      safely combined with 5-FU/LV administered daily for 5 days, every 4 weeks.

PMID- 16406508
TI  - The pharmacokinetics and pharmacodynamics of tandospirone in rats exposed to
      conditioned fear stress.
AB  - The 5-HT1, agonist tandospirone is generally thought to have a weak anxiolytic
      effect with a slow onset of action. Our recent clinical study suggested that a
      comparatively high dose of tandospirone has excellent anxiolytic efficacy and is
      without significant adverse effects. The present study was designed to clarify
      the relationship between the anxiolytic effect of tandospirone and its plasma and
      brain concentrations. The anxiolytic effect was estimated by determining the
      conditioned fear stress-induced freezing behavior in rats after tandospirone
      administration. Obvious correlations between anxiolytic effect and brain
      concentration of tandospirone were observed 0.5 and 4 h after tandospirone
      administration, while the anxiolytic effect was dependent on the plasma
      concentration of at 0.5 h but not 4 h after tandospirone administration. The
      plasma concentration was significantly correlated with the brain concentration.
      These findings suggest that the potency of the anxiolytic effect is dependent on
      both the plasma and brain concentration.

PMID- 16406509
TI  - The influence of friends, family, and older peers on smoking among elementary
      school students: low-risk students in high-risk schools.
AB  - BACKGROUND: This study examined how older smoking peers at school and the smoking
      behaviour of friends and family members are related to youth smoking. METHODS:
      Multi-level logistic regression analysis was used to examine correlates of ever
      smoking in a sample of 4286 grade 6 and 7 students from 57 elementary schools in
      Ontario, Canada (2001). RESULTS: Each 1% increase in the smoking rate among grade
      8 students increased the odds that a student in grades 6 or 7 was an ever smoker
      versus never smoker [OR 1.05, 95% CI 1.02 to 1.08]. A low-risk student (no family
      or friends who smoke) was almost three times more likely to try smoking if he/she
      attended an elementary school with a relatively high prevalence of senior
      students who smoke than if he/she attended a school with a low prevalence of
      senior students who smoke. CONCLUSION: Low-risk grade 6 and 7 students are at
      significantly greater risk of smoking if they attend an elementary school with a
      relatively high prevalence of smoking among senior students. Prevention programs
      should target both at-risk schools and at-risk students.

PMID- 16406510
TI  - Responsiveness to phytoestrogens in primary human osteoblasts is modulated
      differentially by a "less-calcemic" analog of 1,25 dihydroxyvitamin D(3): JK
      1624F(2)-2 (JKF).
AB  - We have reported previously, that female-derived bone cells responded to 17beta
      estradiol (E(2)) and raloxifene (Ral), and male-derived cells responded only to
      dihydrotestosterone (DHT) when the stimulation of creatine kinase specific
      activity (CK), which is a marker for hormone responsiveness, was measured. We
      also found that pre-treatment with the less-calcemic analog of Vitamin D, JK 1624
      F(2)-2 (JKF), upregulated the response of CK to E(2) and Ral. In this study, we
      analyzed the response of human bone cells from pre- and post-menopausal females
      and males, to phytoestrogens. Bone cells derived from pre-menopausal women showed
      greater stimulation of CK than cells from post-menopausal women, after treatment
      with E(2) (30 nM), daidzein (D, 3000 nM), genistein (G, 3000 nM) and Ral (3000
      nM); whereas the responses to biochainin A (BA 3000 nM), quecertin (Qu 3000 nM)
      or the carboxy derivative of G (cG 300 nM) were not age-dependent. Male-derived
      cells did not respond to phytoestrogens. When cells derived from female bones at
      both age groups were pre-treated with JKF, by daily addition of 1nM, for 3 days,
      there was an upregulation of the response to E(2), Ral, G and D but not to BA or
      Qu. Nuclear binding of (3)[H] E(2) was characteristic of the different
      phytoestrogens, with increase of the specific binding after pre-treatment with
      JKF. In contrast, the membranal binding of E(2)-Ov-Eu, which was specific for the
      estrogenic compounds except Ral, was inhibited by pre-treatment with JKF except
      for ICI 161480 (ICI). Male bone cells did not bind E(2)-Ov-Eu but bound T-BSA-Eu;
      this binding was abolished by pre-treatment with JKF. Pre-treatment with JKF
      increased mRNA for ERalpha and decreased mRNA for ERbeta in bone cells from both
      age groups of females and from males, all of which expressed both ERs, with a
      ratio of ERalpha to ERbeta of 121:1 in pre- and 78:1 in post-menopausal and 105:1
      in male bone cells. This study raises the possibility of combined Vitamin D
      analog and phytoestrogen for hormonal replacement therapy to prevent post
      menopausal osteoporosis, which is a subject of ongoing research in animal models.

PMID- 16406511
TI  - Structural and haemovascular aspects of placental growth throughout gestation in
      young and aged mares.
AB  - This investigation was carried out to study the equine placenta from early
      gestation to near term, with special reference to morphological changes
      associated with the development of the vasculature of the fetal component of the
      microcotyledons. Pregnant uteri were removed post mortem from five Thoroughbred
      mares between 110 and 309 days of gestation, two of which were aged, multiparous
      animals suffering age-related degenerative changes in their endometrium
      (endometrosis), while the other three were young, and had primigravid normal
      healthy uteri. Pieces of endometrium with placenta attached were fixed for light
      microscopy and fetal vascular casts were made by injecting the placental arteries
      with a mixture of Mercox and methylmethacrylate. The casts were examined under
      the scanning electron microscope. In an aged, endometrotic mare at 110 days of
      gestation, most of the microplacentomes were irregular in shape with a mean+/-sem
      diameter of 399+/-30.53 microm. Capillaries with variable diameters made up
      widely meshed network villi with pointed ends (Type 1 terminal villi), and narrow
      meshed networks with finger-like ends (Type 2 terminal villi). In the "paired"
      young healthy mare at day 121 of gestation, most of the microplacentomes were
      globular in shape and appeared smaller in diameter than those in the 110-day
      "pair". The narrow-meshed capillary networks formed villi with stems that
      consisted of both intermediate and terminal parts, the latter of which
      represented more the Type 2 than the Type 1 terminal villus. In another aged
      endometrotic mare at 179 days of gestation, the microplacentomes were typically
      globular in shape and they showed a mean diameter of 534+/-36.07 microm. The
      villi were short and thick and they were distinctly differentiated into stem,
      intermediate and terminal parts. The density of the fetal capillaries had now
      greatly increased so that, three dimensionally, they constituted bulb-like
      capillary networks at the base of the stem of each villus. At 199 days in the
      young healthy "pair", the microplacentomes were again smaller in diameter (402+/
      16.24 microm) than in the old mare at 179 days and the interhaemal distance had
      now reduced to 14.28+/-0.42 microm. The vascular density was lower than in the
      day 179 aged mare and the fetal villi were much longer and thinner. In the single
      late stage, healthy young mare at 309 days of gestation (term=336 days), the
      microplacentomes, each of around 2 mm diameter, exhibited maximal length villi.
      The capillaries were arranged simply, mostly in straight lines along the axis of
      the villus, and with communications visible at irregular intervals. Simple and
      slightly more complicated side capillary loops could be seen along the whole
      length of the villi and at the top of the terminal villi. Most of the capillaries
      were characterized by zones containing dilated sinusoids, which increased the
      surface area for materno-fetal exchange. Thus, the morphological development of
      the microplacentomes on the surface of the horse placenta during gestation was
      studied, with special reference to the growth and organisation of the fetal and
      maternal capillary beds within each microplacentome. The study also reinforced
      previous work showing the disadvantageous influence of age-related endometrial
      degenerative changes on microplacentome development and on both the extent and
      intimacy of physical and haematological contact at the fetomaternal interface,
      and hence upon fetal growth.

PMID- 16406512
TI  - Purification and characterization of two endoglucanases from Melanocarpus sp.
      MTCC 3922.
AB  - This study reports the purification and characterization of endoglucanases (EG I
      and EG II) from a newly isolated thermophilic fungus, Melanocarpus sp. MTCC 3922.
      The molecular weight of EG I and EG II as with SDS-PAGE and pI were approximately
      40 and 50 kDa, and approximately 4.0 and 3.6, respectively. EG I and EG II were
      optimally active at 50 and 70 degrees C, and pH 6.0 and 5.0, respectively. EG I
      was active over a broad range of pH (5.0-7.0), whereas, loss of activity was
      observed as the temperature was increased from 50 to 80 degrees C. However, EG II
      was active over pH 4.0-6.0 and temperature 40-80 degrees C. The presence of
      mercaptoethanol and SDS inhibited the EG I activity but showed no negative effect
      on EG II. Both the endoglucanases showed higher activity against barley-beta
      glucan as compared to CMC. Km values of EG I and EG II for barley-beta-glucan
      were lower than CMC. Turn over number (K(cat)) and catalytic efficiency
      (K(cat)/Km) values of both the endoglucanases were higher with barley-beta-glucan
      as substrate than CMC. EG I showed affinity for Avicel indicating the presence of
      cellulose binding domains (CBD) whereas, EG II was found to lack CBD.

PMID- 16406513
TI  - Applications of the CSA-amplified PASS experiment.
AB  - The recently reported CSA-amplified PASS experiment correlates the spinning
      sidebands at the true spinning frequency omega(r) with the spinning sidebands
      that would be obtained at the effective spinning frequency omega(r)/N, where N is
      termed the scaling factor. The experiment is useful for the measurement of small
      chemical shift anisotropies, for which slow magic-angle spinning frequencies,
      required to measure several spinning sidebands, can be unstable. We have
      experimentally evaluated the reliability of this experiment for this application.
      In particular we have demonstrated that large scaling factors of the order of
      N=27 may be used, whilst still obtaining accurate chemical shift sideband
      intensities at the effective spinning frequency from the F(1) projection.
      Moreover, the sideband intensities are accurately obtained even in the presence
      of significant pulse imperfections. A second application of the CSA-amplified
      PASS experiment is the measurement of the chemical shift anisotropy of sites that
      experience homonuclear dipolar coupling, as may be found in uniformly labelled
      biological molecules, or for nuclei with a high natural abundance. The effects of
      homonuclear dipolar coupling on CSA-amplified PASS spectra has been investigated
      by numerical simulations and are demonstrated using uniformly (13)C enriched l
      histidine monohydrochloride monohydrate.

PMID- 16406514
TI  - Hypermethylation of CpG islands in p16 as a prognostic factor for diffuse large B
      cell lymphoma in a high-risk group.
AB  - PURPOSE: The aim of the study was to analyze the methylation status of the
      promoter regions of p15 and p16 and to assess the prognostic significance of
      promoter hypermethylation in diffuse large B-cell lymphoma (DLBCL). EXPERIMENTAL
      DESIGN: DLBCL was diagnosed by morphology and immunohistochemical analysis
      according to the World Health Organization (WHO) classification. The methylation
      status of CpG islands in the p15 and p16 promoters was analyzed by methylation
      specific polymerase chain reaction in 49 DLBCLs. RESULTS: Hypermethylation of the
      p15 and p16 promoters was detected in 20 (41%) and 22 (45%) of the 49 DLBCLs,
      respectively. Among all patients with DLBCL, there was no significant difference
      in the overall survival between those with hypermethylated and unmethylated p15
      (P=0.442) or between those with hypermethylated and unmethylated p16 (P=0.468).
      Therefore, methylation was analyzed in combination with evaluation of clinical
      features using the international prognostic index (IPI). In the high-intermediate
      risk and high-risk groups, patients with hypermethylated p16 had significantly
      lower survival rates than those of patients in the same risk group with
      unmethylated p16 (P=0.010). CONCLUSIONS: Our results suggest that
      hypermethylation of the p16 promoter indicates a poor prognosis in high
      intermediate-risk and high-risk DLBCL patients, and may be a useful marker for
      selection of appropriate treatment when used in conjunction with the IPI.

PMID- 16406515
TI  - Interaction of bulged DNA with leucine-containing mimics of NCS-chrom.
AB  - Synthesis of chiral spirocyclic helical compounds containing leucine that mimic
      the molecular architecture of the potent DNA bulge binder obtained from the
      natural product metabolite NCSi-gb has been accomplished. The interaction between
      the compounds and DNA was studied by circular dichroism (CD) method. The results
      suggested that the two synthetic diastereoisomers specifically targeted the bulge
      site of DNA and induced conformational change of bulged DNA greatly.

PMID- 16406516
TI  - Convenient methods for the synthesis of P1-farnesyl-P2-indicator diphosphates.
AB  - To access P1-farnesyl-P2-indicator diphosphates, more efficient methods for the
      synthesis of farnesyl-phosphate and diphosphates were developed. The procedures
      reported here provide more flexible conditions than the conventional imidazolide
      and morpholidate coupling methods. Milder conditions for the synthesis of
      sensitive allylic diphosphates and greatly improved reaction efficiencies provide
      access to novel reagents for analysis of diphosphate-based enzymatic reactions.

PMID- 16406517
TI  - Microscopic analysis of ester hydrolysis reaction catalyzed by Candida rugosa
      lipase.
AB  - The relationship between the kinetics of the lipase-catalyzed oil hydrolysis and
      the surface area distribution of oil droplets was investigated using ethyl
      decanoate and gum Arabic (GA) as a model oil and an emulsifier, respectively.
      Along an ethyl decanoate concentration gradient between 2 and 8 mM, the initial
      hydrolysis rate increased at 0.25% (w/v) GA but did not change at 1.0% (w/v) GA.
      At 0.25% GA, the surface area of droplets was narrowly distributed regardless of
      the ethyl decanoate concentration. However, at 1.0% GA and with ethyl decanoate
      concentrations higher than 2 mM, the fraction of relatively large droplets with a
      surface area larger than approximately 200 microm2, suddenly increased. The
      microscopy of ethyl decanoate emulsion during the hydrolysis reaction indicates
      that the large oil droplets were not hydrolyzed. At 20 mM ethyl decanoate where
      the hydrolysis rate remained the same between 0.25% and 1.0% GA, the surface area
      of droplets was narrowly distributed at 0.25% and 1.0% GA. Therefore, the
      constant hydrolysis rate observed in the emulsion of ethyl decanoate between 2
      and 8 mM containing GA at 1.0%, is believed to be caused by the relatively large
      oil droplets with the interface quality differing from that of the small oil
      droplets.

PMID- 16406518
TI  - Characterization of phospholipid+semifluorinated alkane vesicle system.
AB  - The aim of this study is to characterize vesicles obtained by the incorporation
      of the semifluorinated alkane, (perfluoro-n-hexyl)ethane (diblock F6H2) to a
      standard lipid, egg yolk phosphatidylcholine (PC). Large unilamellar vesicles
      (LUVs), prepared by extrusion, were characterized by fluorescence spectroscopy,
      zeta potential (zeta-potential) and light scattering. By using the fluorescence
      spectroscopy technique, the anisotropy of l,6-diphenyl-l,3,5-hexatriene (DPH)
      probe at different temperatures was determined. It was demonstrated that F6H2 is
      placed inside of the lipid bilayer and that the hydrocarbon acyl chain in the
      bilayers has higher viscosity in the presence of fluoroalkane. The zeta-potential
      of the PC-F6H2 system is negative and increases (in absolute value) from -10 to 
      19 mV when the temperature rises from 10 to 25 degrees C, this last value keeping
      practically constant with a further increase of temperature. The adsorption of K+
      ions on the liposome surface was measured by zeta-potential. This adsorption
      originates a sudden increase of the initial zeta-potential followed by a slight
      decrease with K+ concentration. The application of the DLVO theory of colloidal
      stability showed a growing dependence of the DLVO potential with K+ concentration
      and consequently a increasing stability.

PMID- 16406519
TI  - Investigation on the interaction between colloidal gold and human complement
      factor 4 at different pH by spectral methods.
AB  - The interaction between colloidal gold and human complement factor 4 (human C4)
      at different pH was investigated by spectral methods, including absorption and
      resonance light-scattering spectrometry. According to the changes of color and
      absorption spectra of colloidal gold solution in presence of human C4, the
      interaction between colloidal gold and human C4 was quantitatively investigated
      using a semi-empirical "flocculation parameter". At the same time, the changes of
      resonance light-scattering spectra and transmission electron microscopy (TEM)
      images indicate that the aggregation of colloidal gold happens by electrostatic
      interaction in presence of human C4 in the pH range 5-6. However, the colloidal
      gold solution remains stable at pH >6 and pH <5 due to the repulsive
      electrostatic interaction between colloidal gold and human C4. The flocculation
      parameter is directly proportional to the concentration of human C4 in the range
      from 9.7 to 233.0 microgl(-1). In addition, the interactions between the
      colloidal gold and bovine serum albumin (BSA) as well as human serum albumin
      (HSA) were also investigated using the same methods. It was found that there was
      no aggregation of colloidal gold in presence of BSA and HSA in the pH range 5-6.
      However, when the pH of solution is 4, the aggregation of colloidal gold happens.
      Because BSA and HSA have different structure, the intensity of aggregation of
      colloidal gold in presence of BSA is greater than that in presence of HSA at pH
      4.

PMID- 16406520
TI  - In vivo cell biology: following the zebrafish trend.
AB  - A deeper understanding of the mechanisms of cell behavior is essential if we want
      to comprehend how an organism develops and functions. Changes in cellular
      processes, including the orientation of cell divisions, cell shape, polarity,
      differentiation and migration, account for tissue rearrangements during
      development and homeostasis. The in vivo relevance of in vitro findings is being
      constantly debated and the need for in vivo systems becoming more pressing. The
      zebrafish (Danio rerio) might become the vertebrate system of choice for a wide
      spectrum of biological questions that need to be investigated in vivo at cellular
      and subcellular resolutions. Here, we discuss some recent studies in which the
      zebrafish was used to gain insight into cell-biological mechanisms. Although this
      model system has been predominantly appreciated for its amenability to forward
      genetics, current advances in imaging technology and an increasing number of
      transgenic lines are bringing it closer to its full potential.

PMID- 16406521
TI  - Osteopontin: role in cell signaling and cancer progression.
AB  - Cell migration and degradation of the extracellular matrix (ECM) are crucial
      steps in tumor progression. Several matrix-degrading proteases, including matrix
      metalloproteases, are highly regulated by growth factors, cytokines and ECM
      proteins. Osteopontin (OPN), a chemokine-like, calcified ECM-associated protein,
      plays a crucial role in determining the metastatic potential of various cancers.
      Since its first identification in bone, the multifaceted roles of OPN have been
      an area of intense investigation. Extensive research has elucidated the pivotal
      role of OPN in regulating the cell signaling that controls tumor progression and
      metastasis. This review focuses on recent advances in understanding the
      functional role of the OPN-induced signaling pathway in the regulation of cell
      migration and tumor progression and the implications for identifying novel
      targets for cancer therapy.

PMID- 16406522
TI  - Modeling mitosis.
AB  - The mitotic spindle is a fascinating protein machine that uses bipolar arrays of
      dynamic microtubules and many mitotic motors to coordinate the accurate
      segregation of sister chromatids. Here we discuss recent mathematical models and
      computer simulations that, in concert with experimental studies, help explain the
      molecular mechanisms by which the spindle machinery performs its crucial
      functions. We review current models of spindle assembly, positioning, maintenance
      and elongation; of chromosome capture and congression; and of the spindle
      assembly checkpoint. We discuss some limitations of the application of modeling
      to other aspects of mitosis and the feasibility of building more comprehensive
      system-level models.

PMID- 16406523
TI  - Daxx: death or survival protein?
AB  - The death domain-associated protein (Daxx) was originally cloned as a CD95 (FAS)
      interacting protein and modulator of FAS-induced cell death. Daxx accumulates in
      both the nucleus and the cytoplasm; in the nucleus, Daxx is found associated with
      the promyelocytic leukaemia (PML) nuclear body and with alpha-thalassemia/mental
      retardation syndrome protein (ATRX)-positive heterochromatic regions. In the
      cytoplasm, Daxx has been reported to interact with various proteins involved in
      cell death regulation. Despite a significant number of studies attempting to
      determine Daxx function in apoptotic and non-apoptotic cell death, its precise
      role in this process is only partially understood. Here, we critically review the
      current understanding of Daxx function and shed new light on this interesting
      field.

PMID- 16406524
TI  - Retrograde transport on the COG railway.
AB  - The conserved oligomeric Golgi (COG) complex is essential for establishing and/or
      maintaining the structure and function of the Golgi apparatus. The Golgi
      apparatus, in turn, has a central role in protein sorting and glycosylation
      within the eukaryotic secretory pathway. As a consequence, COG mutations can give
      rise to human genetic diseases known as congenital disorders of glycosylation. We
      review recent results from studies of yeast, worm, fly and mammalian COG that
      provide evidence that COG might function in retrograde vesicular trafficking
      within the Golgi apparatus. This hypothesis explains the impact of COG mutations
      by postulating that they impair the retrograde flow of resident Golgi proteins
      needed to maintain normal Golgi structure and function.

PMID- 16406525
TI  - Ten challenges for improved ecotoxicological testing in environmental risk
      assessment.
AB  - New regulations, in particular the new European chemicals legislation (REACH),
      will increase the demands on environmental risk assessment (ERA). The
      requirements on efficient ecotoxicological testing systems are summarized, and 10
      major issues for the improvement of ERA practices are discussed, namely: (1) the
      choice of representative test species, (2) the development of test systems that
      are relevant for ecosystems in different parts of the world, (3) the inclusion of
      sensitive life stages in test systems, (4) the inclusion of endpoints on genetic
      variation in populations, (5) using mechanistic understanding of toxic effects to
      develop more informative and efficient test systems, (6) studying disruption in
      invertebrate endocrine mechanisms, that may differ radically from those we know
      from vertebrates, (7) developing standardized methodologies for testing of poorly
      water-soluble substances, (8) taking ethical considerations into account, in
      particular by reducing the use of vertebrates in ecotoxicological tests, (9)
      using a systematic (statistical) approach in combination with mechanistic
      knowledge to combine tests efficiently into testing systems, and (10) developing
      ERA so that it provides the information needed for precautionary decision-making.

PMID- 16406526
TI  - Solubilization behavior of a poorly soluble drug under combined use of
      surfactants and cosolvents.
AB  - The solubilization behavior of a poorly soluble model drug, phenytoin (PHT),
      under combined use of surfactants (sodium dodecyl sulfate (SDS), Tween 80) and
      cosolvents (dimethylacetoamide (DMA), ethanol, poly(ethylene glycol) 400 (PEG),
      glycerol) was examined. The solubility of PHT in the aqueous surfactant solutions
      increased linearly with increase of the surfactant concentration. The solubility
      of PHT in water-cosolvent mixtures roughly followed the log-linear model, which
      is widely accepted to explain the solubilization behavior of poorly soluble
      compounds in water-cosolvent mixtures, except for the case of glycerol, in which
      the solubility was minimal at 10% (w/v) of glycerol. When the cosolvents were
      added to the aqueous surfactant solutions, their effect on the solubility
      depended on the combination of the surfactant and the cosolvent. The most
      striking increase in solubility was observed with DMA, regardless of the type of
      surfactant. When ethanol was added, an increase in the solubility was observed
      with the Tween 80 solution, while a dramatic decrease was found with the SDS
      solution. The addition of glycerol or PEG to the surfactant solutions had only a
      minor impact on the solubility. These solubilization behaviors of PHT in the
      surfactant-cosolvent mixtures were partially explained by the solubility model
      introduced in our previous paper [Kawakami, K., Miyoshi, K., Ida, Y., 2004.
      Solubilization behavior of poorly soluble drugs with combined use of Gelucire
      44/14 and cosolvent. J. Pharm. Sci. 93, 1471-1479]. Addition of the cosolvents to
      the surfactant solutions generally offered only a small advantage from the
      viewpoint of improving solubility because of the decrease in the solubilization
      capacity of the micelles.

PMID- 16406527
TI  - Initial repertoire of anti-(4-hydroxy-3-nitrophenylacetyl) antibodies as
      potential donors for effective affinity maturation.
AB  - We previously found that there are two distinct antibody (Ab) maturation pathways
      for the immune response of C57BL/6 mice to 4-hydroxy-3-nitrophenylacetyl (NP),
      one involving Abs with high evolvability (group-H) and the other involving Abs
      with low evolvability (group-L). Commitment to whichever pathway is followed pre
      determined in B cells at an early developmental stage. Candidates for the group-L
      or -H pathway are thus expected to pre-exist in the initial repertoire of the
      immune response. In the present study, we examined the initial Ab repertoire from
      the viewpoint of the latent potential of these Abs for effective affinity
      maturation. At first, we prepared anti-NP B cell hybridomas at 1 week
      postimmunization. Although the diversity of the obtained repertoire was
      maintained mainly by the third complementarity determining region of the heavy
      chain (CDR-H3), their changes in the near UV circular dichroism resulting from NP
      binding allowed for classification into three groups according to the same rules
      applied in the pathway classification of the maturated Abs. This suggested that
      the innate structural properties of CDR-H3 were conserved throughout maturation.
      In other words, in exploring the structure of CDR-H3, it is possible to
      distinguish the latent potentials of Abs in effective affinity maturation even
      those making up the initial Ab repertoire. We then examined an artificially
      designed group-H Ab prototype and found its NP-binding ability sufficient for
      engagement in the initial repertoire. The question arose here as to why the
      majority of the actual initial repertoire consisted of the group-L ancestors
      regardless of their middling NP-binding affinity, which called for further
      discussion from the viewpoint of the dynamics possibly shaping the repertoire.

PMID- 16406528
TI  - Beyond diversity: functional microbiomics of the human colon.
AB  - Molecular tools have revealed wide microbial diversity in the human alimentary
      tract. Most intestinal microorganisms have not been cultured and the in situ
      functions of distinct groups of the intestinal microbiota are largely unknown but
      pivotal to understanding the role of these microorganisms in health and disease.
      Promising strategies to gain more insight into the functionality of the complex
      microbial communities in the human alimentary tract, including fermentation
      processes in the colon, are discussed. These research approaches could provide a
      basis for the definition of a healthy gut based on key properties of microbial
      functionality. This will also enable the development of direct nutritional
      strategies for intestinal disease prevention and health promotion.

PMID- 16406529
TI  - Why do microorganisms have aquaporins?
AB  - Aquaporins are channel proteins that enhance the permeability of cell membranes
      for water. They have been found in Bacteria, Archaea and Eukaryotes. However,
      their absence in many microorganisms suggests that aquaporins do not fulfill a
      broad role such as turgor regulation or osmoadaptation but, instead, fulfill a
      role that enables microorganisms to have specific lifestyles. The recent
      discovery that aquaporins enhance cellular tolerance against rapid freezing
      suggests that they have ecological relevance. We have identified several examples
      of large-scale freeze-thawing of microbes in nature and we also draw attention to
      alternative lifestyle-related functions for aquaporins, which will be a focus of
      future research.

PMID- 16406531
TI  - Filter-feeding dabbling ducks (Anas spp.) can actively select particles by size.
AB  - The relationship between bill morphology, function and prey use among filter
      feeding dabbling ducks (Anas spp.) is poorly understood. In particular, it is not
      clear if interspecific differences in morphology affect the retention of prey to
      allow prey partitioning. The size of particles retained by ducks may be
      determined entirely by the distance between adjacent mandibular lamellae
      (interlamellar distance), possibly allowing interspecific partitioning of prey by
      size. Alternatively, articulation of the maxilla and mandible allows ducks to
      increase the distance between the maxillary and mandibular lamellae (lamellar
      separation) so that it exceeds their interlamellar distance, possibly allowing
      them to selectively expel unwanted particles larger than their interlamellar
      distance. In contrast, if interlamellar distance alone determines the size of
      particles ingested, particles larger than the interlamellar distance will always
      be retained because lamellar spacing is fixed. When large, preferred millet and
      wheat seeds were mixed with small, less preferred poppy seeds, all three ducks in
      this investigation ingested a greater proportion of the millet and wheat seeds
      than the poppy seeds, even though all three seed types were larger than the
      ducks' interlamellar distance. The proportion of millet and poppy seeds ingested
      when seeds were mixed differed from the proportion expected from foraging rates
      on unmixed prey, indicating the ducks actively avoided poppy seeds. These results
      are consistent with the lamellar separation hypothesis and clearly reject the
      singular role of interlamellar distance in prey retention. Because lamellar
      separation and water filtration rate are both determined by movement of the
      maxilla and mandible, there may be a trade-off between particle size selection
      and prey ingestion rate that allows interspecific partitioning of prey by size.

PMID- 16406532
TI  - Transmembrane protein structures without X-rays.
AB  - Transmembrane (TM) proteins constitute 15-30% of the genome, but <1% of the
      structures in the Protein Data Bank. This discrepancy is disturbing, and
      emphasizes that structure determination of TM proteins remains challenging. The
      challenge is greatest for proteins from eukaryotes, the structures of which
      remain intractable despite tremendous advances that have been made towards
      structure determination of bacterial TM proteins. Notably, >50% of the membrane
      protein families in eukaryotes lack bacterial homologs. Therefore, it is
      conceivable that many more years will elapse before high-resolution structures of
      eukaryotic TM proteins emerge. Until then, integrated approaches that combine
      biochemical and computational analyses with low-resolution structures are likely
      to have increasingly important roles in providing frameworks for the mechanistic
      understanding of membrane-protein structure and function.

PMID- 16406533
TI  - Comparison of 2D reconstructions of surgically excised subfoveal choroidal
      neovascularization with fluorescein angiographic features: SST report No. 15.
AB  - OBJECTIVES: To compare topographic features of surgically excised subfoveal
      choroidal neovascularization with preoperative and postoperative fluorescein
      angiographic features from Submacular Surgery Trials (SST) patients, and to
      compare histological and angiographic features with preoperative and
      postoperative visual acuities (VAs). METHODS: Patients enrolled in the SST Groups
      N, B, and H trials between October 1999 and September 2001 and assigned to the
      surgery arm had surgically removed choroidal neovascularization sent to the SST
      Pathology Center. Grossly intact specimens were sectioned serially for 2
      dimensional reconstruction and were assigned to growth pattern groups based on
      topographic mapping of the location of cellular components relative to the
      retinal pigment epithelium (RPE): sub-RPE, subretinal, combined, or
      indeterminate. These features were compared with preoperative fluorescein
      angiographic features. The histological choroidal neovascularization growth
      pattern was compared with preoperative VAs. RESULTS: Two-dimensional
      reconstructions of surgically excised choroidal neovascularization could not be
      matched point for point to fluorescein angiographic features. Among the 52
      specimens selected, the growth pattern could be determined by 2-dimensional
      reconstruction in 34 instances (65%), including 28 (80%) of 35 Group N specimens,
      2 (40%) of 5 Group B specimens, and 4 (33%) of 12 Group H specimens. Among the
      choroidal neovascularization growth patterns that could be determined from
      specimens submitted, the majority of Group N specimens were combined, and the
      majority of Group H specimens were subretinal. In most instances for Group B
      specimens, the growth pattern was indeterminate. The postoperative abnormalities
      on fluorescein angiography were generally larger than measurements of excised
      specimens. The subretinal growth pattern was associated with the smallest
      decrease in 3-month postoperative average VA. CONCLUSIONS: Among the 52 specimens
      from the SST with adequate tissue to try to evaluate the growth pattern of the
      neovascular lesion, 34 had patterns that could be determined. The subretinal
      growth pattern tended to correspond with lesions that were classic choroidal
      neovascularization without occult choroidal neovascularization on fluorescein
      angiography. The most favorable visual outcome occurred if the choroidal
      neovascularization had a subretinal growth pattern. The combined growth pattern
      tended to correspond with lesions on fluorescein angiography that had both
      classic choroidal neovascularization and occult choroidal neovascularization. The
      conclusions must be viewed within the context that 18 (35%) of the 52
      participants could not be characterized for histologic growth pattern.

PMID- 16406534
TI  - Linear basal cell carcinoma: a distinct clinical entity in the periocular region.
AB  - PURPOSE: To report periocular linear basal cell carcinoma (BCC) as a distinct
      clinical entity, and to highlight its existence in the ophthalmic literature.
      DESIGN: Retrospective, noncomparative, multicenter, interventional small case
      series. PARTICIPANTS: Four patients with linear BCC in the periocular region.
      INTERVENTION: All patients underwent margin-controlled excision, 3 utilizing
      Mohs' micrographic surgery and 1 using frozen section. MAIN OUTCOME MEASURES:
      Age, gender, location, preoperative tumor size, histological growth pattern,
      presence of perineural invasion, number of Mohs' levels used to obtain histologic
      clearance, postoperative defect size, and recurrence. RESULTS: In all 4 cases,
      the site of occurrence was in the lower eyelid and cheek. Histology revealed
      pigmented nodular BCC with an infiltrative component in 2 cases and nodular BCC
      in the remaining 2 cases. No perineural invasion was noted in any of the cases.
      Two Mohs' levels were required for complete excision in 3 patients. CONCLUSIONS:
      Linear BCC is a distinct clinical entity. Presence of the tumor along relaxing
      skin tension lines, increase in subclinical extension, and aggressive tumor
      behavior are reported observations. Because of these observations, it is
      suggested that margin-controlled excision should be considered for linear BCC.

PMID- 16406535
TI  - Clinical ability of pattern electroretinograms and visual evoked potentials in
      detecting visual dysfunction in ocular hypertension and glaucoma.
AB  - OBJECTIVE: To assess the presence of normal or abnormal pattern electroretinogram
      (PERG) and visual evoked potential (VEP) responses in patients with ocular
      hypertension or open-angle glaucoma (OAG). DESIGN: Retrospective, cross
      sectional, case-control study. PARTICIPANTS: Eighty normal control subjects (mean
      age, 51.77+/-6.04 years; 80 eyes), 68 ocular hypertension patients (mean age,
      51.58+/-7.12; 68 eyes; intraocular pressure [IOP] < 18 mmHg under pharmacological
      treatment; Humphrey field analysis [HFA] 24/2 mean deviation [MD] > -2 decibels
      [dB]), and 84 OAG patients (mean age, 52.77+/-5.28; 84 eyes; IOP < 18 mmHg under
      pharmacological treatment; HFA 24/2 mean deviation between -2 and -23 dB) were
      enrolled. METHODS: Simultaneous recording of PERGs and VEPs using high-contrast
      (80%) 15' checkerboard stimuli reversed at the rate of 2 reversals per second.
      MAIN OUTCOME MEASURES: Pattern electroretinogram P50 and VEP P100 implicit times
      were considered delayed when exceeding the limit of mean values of controls plus
      2 standard deviations (SDs). Pattern electroretinogram P50 to N95 and VEP N75 to
      P100 amplitudes were considered reduced when exceeding the limit of mean values
      of controls minus 2 SDs. RESULTS: Pattern electroretinogram: P50 implicit times
      were delayed in 58 of 68 (85.30%) ocular hypertension eyes and 83 of 84 (98.80%)
      OAG eyes; P50 to N95 amplitudes were reduced in 47 (69.12%) ocular hypertension
      eyes and 84 (100%) OAG eyes. Visual evoked potential: P100 implicit times were
      delayed in 58 (85.30%) ocular hypertension eyes and 84 (100%) OAG eyes; reduced
      N75 to P100 amplitudes were observed in 39 (57.35%) ocular hypertension eyes and
      73 (86.90%) OAG eyes. Ocular hypertension eyes showed no significant correlations
      (Pearson test, P>0.01) between electrophysiological parameters and age, IOP
      before or under medical treatment, HFA, and corneal thickness values. Significant
      correlations (P<0.01) were observed in OAG eyes between electrophysiological
      results and HFA values. Pattern electroretinogram and VEP responses were normal
      in all control eyes. CONCLUSIONS: Combined PERG/VEP recordings identified a large
      percentage of ocular hypertension eyes with impairment of the innermost retinal
      layers, notwithstanding normal optic disc morphology and normal HFA. In OAG eyes,
      PERG P50 to N95 amplitude and VEP P100 implicit time showed the highest
      sensitivity/specificity for the detection of a visual dysfunction. The presence
      of abnormal PERG and/or VEP responses did not allow a clearcut separation between
      ocular hypertension and OAG eyes.

PMID- 16406537
TI  - Asymmetry of right versus left intraocular pressures over 24 hours in glaucoma
      patients.
AB  - PURPOSE: To assess the asymmetry of 24-hour intraocular pressures (IOPs) between
      right and left eyes of untreated open-angle glaucoma (OAG) patients, and its
      influence on the monocular therapeutic trial. DESIGN: Experimental study with
      human patients. PARTICIPANTS: Forty-one subjects (40-78 years old) with untreated
      OAG. METHODS: Subjects were housed in a sleep laboratory for 24 hours.
      Intraocular pressures of both eyes were measured with a pneumatonometer every 2
      hours with the patient in the sitting and supine positions from 7 am to 11 pm and
      in the supine position only from 11 pm to 7 am. Mean, peak, and trough IOPs were
      compared in right versus left eyes. The strength of association between right and
      left IOPs was assessed using coefficients of determination (R2). Validity of the
      monocular therapeutic trial was assessed by examining residual values from 2
      linear regression models of right versus left IOP. MAIN OUTCOME MEASURES:
      Strength of association between IOPs of right and left eyes, and residual values
      from linear models of IOP. RESULTS: No statistically significant difference was
      found between mean, peak, or trough IOPs of right and left eyes over a 24-hour
      period. The strength of association for mean IOP was only moderate (R(2) = 0.421
      0.623). Residual values of > or =3 mmHg were found in 14.0%+/-12.0% (mean +/-
      standard deviation) of IOP measurements for a symmetric linear regression model,
      and 8.5%+/-10.6% of IOP measurements for a best-fit linear regression model over
      24 hours. CONCLUSIONS: In this group of untreated glaucoma patients, the strength
      of association between the right and left eye mean IOPs is only moderate.
      Residual values of > or =3 mmHg were more common using a symmetric model than
      with a best-fit model. The current method of performing monocular therapeutic
      trials in glaucoma patients is unreliable, but it may be possible to improve
      reliability by using several IOP measurements obtained at different times of the
      day instead of a single office measurement.

PMID- 16406536
TI  - Visual acuity in children with glaucoma.
AB  - PURPOSE: To investigate the risk factors that influence outcome of visual
      function in children with glaucoma. DESIGN: Retrospective noncomparative
      interventional case series. PARTICIPANTS: One hundred twenty-six patients (204
      eyes) who had childhood glaucoma observed over 30 years, with a mean follow-up of
      11.6 years. INTERVENTIONS: Full ophthalmologic examination, including measurement
      of corrected visual acuity (VA), slit-lamp and fundus examinations, intraocular
      pressure (IOP) measurement, and gonioscopic evaluation; periodic cycloplegic
      refraction and perimetry; and treatment of amblyopia. MAIN OUTCOME MEASURES: Type
      of glaucoma; final best-corrected VA of good (6/6-6/12), fair (6/15-6/30), or
      poor (< or =6/60); patient age at time of development of glaucoma complications;
      and percentage of IOP measurements of < or =19 mmHg, perimetry results, and cup
      to-disc (C/D) ratio during follow-up. RESULTS: The most recently measured VAs of
      children treated for glaucoma were good in 29%, fair in 24%, and poor in 47%. The
      most favorable outcome was for patients with primary infantile glaucoma followed
      by secondary glaucoma. Amblyopia and optic nerve damage due to glaucoma were the
      most frequent complications affecting VA. Patients with an IOP of < or =19 mmHg
      on 80% of determinations had stable optic nerve C/D ratios and visual fields.
      CONCLUSIONS: Vision sufficient to qualify for a motor vehicle driving license was
      attainable in almost 30% of affected eyes. Visual acuity achieved at 6 years of
      age remained stable over the study period. Treatment of amblyopia is important to
      achieve this result.

PMID- 16406538
TI  - Management of retinal detachment when no break is found.
AB  - OBJECTIVE: To review the results of 2 different surgical approaches in the
      management of primary rhegmatogenous retinal detachments (RDs) with undetected
      retinal breaks. DESIGN: Retrospective, consecutive, interventional case series.
      PARTICIPANTS: Medical records of 44 patients with uncomplicated macula-involving
      primary rhegmatogenous-appearing RDs, but without retinal breaks detected
      preoperatively or intraoperatively, were reviewed. METHODS: All study patients
      were operated by the same surgeon between 1989 and 2004 using 2 approaches: 26
      (59%) patients underwent a scleral buckling procedure (SBP) with or without
      subretinal fluid drainage, whereas 18 (41%) patients underwent scleral buckling
      combined with pars plana vitrectomy (PPV), fluid-gas exchange, and broad
      application of endolaser. MAIN OUTCOME MEASURES: Single operation and final
      postoperative anatomic success, and 2-month postoperative and final best
      corrected visual acuity (VA) (negative logarithm of the minimum angle of
      resolution [logMAR]). RESULTS: Mean preoperative VAs were 1.73 logMAR units
      (median, 1.60; range, 0.48-2.60) in the combined surgery group and 1.52 logMAR
      units (median, 1.30; range, 0.30-2.60) in the scleral buckling group. Neither
      preoperative (P = 0.33), 2-month postoperative (P = 0.53), best-corrected (P =
      0.98), nor final (P = 0.46) mean VA showed any statistically significant
      differences between the 2 treatment groups. A single operation reattachment rate
      of 72% (13/18 cases) was achieved in the combined surgery group, compared with
      61.5% (16/26 cases) in the scleral buckling group (P = 0.17, log rank test).
      Immediate anatomic success rates were 89% after combined treatment and 38.5%
      after scleral buckling alone (P = 0.002). At the final visit, the retina was
      attached in 15 (83.3%) patients who received the combined treatment and in 22
      (84.6%) patients who underwent scleral buckling (P = 0.900). Intraoperative
      subretinal hemorrhage occurred in 1 (5.6%) patient from the combined surgery
      group and in 2 (7.7%) patients from the scleral buckling group. Retinal
      incarceration in the drainage sclerotomy occurred in 1 (3.8%) case during the
      SBP. Proliferative vitreoretinopathy sufficient to require reoperation developed
      in 1 (5.6%) eye of the combined surgery group and in 3 (11.5%) eyes of the
      scleral buckling group. CONCLUSIONS: Scleral buckling is as effective in the
      management of uncomplicated rhegmatogenous RDs with undetected breaks as is
      surgery combining scleral buckling and PPV.

PMID- 16406540
TI  - Compressive optic neuropathy after use of oxidized regenerated cellulose in
      orbital surgery: review of complications, prophylaxis, and treatment.
AB  - PURPOSE: We report 2 cases of compressive optic neuropathy after use of oxidized
      regenerated cellulose (ORC) in orbital surgery. To our knowledge, no
      complications have been reported previously after use of this material in orbital
      surgery. We also review the complications related to its retention at operative
      sites outside the orbit and recommend precautions to avoid them. DESIGN:
      Retrospective interventional case reports. PARTICIPANTS: Two patients with
      compressive optic neuropathy after use of ORC in orbital surgery. METHODS: Case
      reports from 2 different clinics and review of the English scientific literature.
      MAIN OUTCOME MEASURES: Best-corrected visual acuity, extraocular motility,
      proptosis, and chemosis. RESULTS: One patient underwent orbital exploration and
      biopsy of an orbital tumor, and the second had repair of an orbital floor
      fracture. Postoperatively, both presented with chemosis, ophthalmoplegia, and
      progressive loss of vision. Orbital imaging revealed a retrobulbar soft-tissue
      density compatible with hematoma. Repeat orbital exploration revealed the soft
      tissue mass to be swollen ORC. CONCLUSIONS: Retained intraorbital ORC may cause a
      compartment syndrome and should be suspected in postoperative patients with
      orbital symptoms. When ORC is used around the optic nerve, it should be removed
      after hemostasis is achieved.

PMID- 16406539
TI  - Relation of visual function to retinal nerve fiber layer thickness in multiple
      sclerosis.
AB  - PURPOSE: To examine the relation of visual function to retinal nerve fiber layer
      (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis
      (MS), and to compare RNFL thickness among MS eyes with a history of acute optic
      neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON
      eyes), and disease-free control eyes. DESIGN: Cross-sectional study.
      PARTICIPANTS: Patients with MS (n = 90; 180 eyes) and disease-free controls (n =
      36; 72 eyes). METHODS: Retinal never fiber layer thickness was measured using
      optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision
      testing was performed for each eye and binocularly before OCT scanning using
      measures previously shown to capture dysfunction in MS patients: (1) low-contrast
      letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2)
      contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated
      Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and
      protocol refractions were performed. MAIN OUTCOME MEASURES: Retinal nerve fiber
      layer thickness measured by OCT, and visual function test results. RESULTS:
      Although median Snellen acuity equivalents were better than 20/20 in both groups,
      RNFL thickness was reduced significantly among eyes of MS patients (92 mum)
      versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes
      (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye
      correlations). Lower visual function scores were associated with reduced average
      overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast
      letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by
      4 mum. CONCLUSIONS: Scores for low-contrast letter acuity and contrast
      sensitivity correlate well with RNFL thickness as a structural biomarker,
      supporting validity for these visual function tests as secondary clinical outcome
      measures for MS trials. These results also suggest a role for ocular imaging
      techniques such as OCT in trials that examine neuroprotective and other disease
      modifying therapies. Although eyes with a history of acute optic neuritis
      demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less
      RNFL thickness than controls, suggesting the occurrence of chronic axonal loss
      separate from acute attacks in MS patients.

PMID- 16406541
TI  - Uveitis in the elderly: epidemiological data from the National Long-term Care
      Survey Medicare Cohort.
AB  - PURPOSE: There is a paucity of population-based data on the epidemiology of
      uveitis in the elderly. In the past 40 years, only 2 U.S. population-based
      studies have examined the epidemiology of uveitis. The conclusions of these
      studies on the burden of uveitis in the elderly differ greatly. In this analysis,
      we use Medicare claims data to define the population-based incidence and
      prevalence of uveitis in the United States elderly population. DESIGN: Cohort
      study. PARTICIPANTS: A cohort of 21644 Medicare beneficiaries drawn for the
      National Long-term Care Survey, a random sample of U.S. adults 65 years and
      older, was followed up from 1991 through 1999. METHODS: The International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes
      specific to uveitis were queried. To decrease the inclusion of uveitis caused by
      surgery, diagnoses occurring within 3 months of intraocular surgery were
      excluded. The incidence and prevalence of uveitis by anatomic location was
      calculated for each year in the study. MAIN OUTCOME MEASURES: The onset of
      uveitis during a given year and its presence in subsequent years. RESULTS: The
      cumulative yearly incidence of uveitis ranged from 302/100000 to 424/100000
      persons per year and averaged 340.9/100000 persons per year. Anterior uveitis was
      the most common form of uveitis in this population, with a mean incidence of
      243.6 cases per 100000 persons per year. The incidence of posterior uveitis
      averaged 76.6/100000 and the incidence of panuveitis/endophthalmitis averaged
      41.7/100000. Only 2 cases of intermediate uveitis occurred during the study
      period. The cumulative prevalence of uveitis doubled from 511/100000 in 1991 to
      1231/100000 in 1999, with anterior uveitis accounting for most prevalent cases in
      every year. CONCLUSIONS: The burden of uveitis in the elderly is substantial and
      is higher than previously thought. Longitudinal analysis of Medicare claims data
      may provide a useful tool for monitoring uncommon diseases, such as uveitis, in
      the elderly population.

PMID- 16406542
TI  - Errors in retinal thickness measurements obtained by optical coherence
      tomography.
AB  - OBJECTIVE: To report the frequency and severity of optical coherence tomography
      (OCT) retinal thickness measurement errors and to describe parameters that
      predict these errors. DESIGN: Observational case series. PARTICIPANTS: Two
      hundred consecutive patients undergoing OCT imaging. METHODS: One eye (primary)
      from each of 200 consecutive patients undergoing Stratus OCT imaging (Carl Zeiss
      Meditec, Dublin, CA) with radial lines or fast macular thickness-based
      acquisition protocols was selected for review by 2 graders. On each of the line
      scans, graders evaluated the position of the automated retinal boundary lines
      (inner retinal surface and retinal pigment epithelium band) used by the OCT
      machine for thickness calculations and graded the positioning on a 6-point
      subjective, categorical error scale to generate an error score. The presence of
      thickness errors was correlated with various parameters, including the analysis
      confidence assessment reported by the OCT software, disease diagnosis, retinal
      morphologic features, the foveal center thickness standard deviation (FCTSD), and
      the FCTSD-to-foveal center thickness (FCT) ratio. MAIN OUTCOME MEASURE: Average
      OCT retinal thickness error score. RESULTS: Errors of retinal boundary detection
      and thickness measurement were observed in 92% of eyes, but were severe in only
      13.5% of eyes. The identification of an error or low analysis confidence by the
      OCT software was strongly associated with the severity of the retinal thickness
      errors. A higher FCTSD-to-FCT ratio and presence of subretinal fluid also were
      associated with more severe errors. Retinal cysts and a diagnosis of retinal
      vascular disease such as diabetic macular edema were less likely to be associated
      with significant errors. CONCLUSIONS: Retinal thickness measurement errors occur
      frequently with current OCT segmentation and analysis algorithms. Severe errors
      are more frequent in eyes with subretinal pathologic features, but generally are
      detected by the OCT software. A high FCTSD-to-FCT ratio (>0.1) also may alert the
      clinician to the possibility of thickness errors. Clinical studies, particularly
      those pertaining to subretinal diseases, should consider these errors when
      incorporating OCT imaging in the study design.

PMID- 16406543
TI  - Vitreous levels of pigment epithelium-derived factor and vascular endothelial
      growth factor are related to diabetic macular edema.
AB  - PURPOSE: To investigate whether vitreous levels of vascular endothelial growth
      factor (VEGF) and pigment epithelium-derived factor (PEDF) are related to
      diabetic macular edema (DME). DESIGN: Retrospective case-control study.
      PARTICIPANTS: Thirty-six patients with DME, 6 diabetic patients without
      retinopathy, and 13 patients with nondiabetic ocular disease. METHODS: After
      vitreous fluid samples were obtained at vitreoretinal surgery, VEGF and PEDF
      levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay.
      MAIN OUTCOME MEASURES: Correlations between vascular permeability and the
      vitreous fluid levels of VEGF and PEDF. RESULTS: The vitreous level of VEGF was
      significantly higher in patients with DME than in nondiabetic patients and
      diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively).
      Conversely, the vitreous level of PEDF was significantly lower in patients with
      DME than in nondiabetic patients and diabetic patients without retinopathy
      (P<0.0001 and P<0.0001, respectively). The vitreous level of PEDF did not
      correlate significantly with that of VEGF (P = 0.1806). The vitreous level of
      VEGF was significantly higher in patients with hyperfluorescent DME than in those
      with minimally fluorescent DME (P = 0.0022). Conversely, the vitreous PEDF level
      was significantly lower in patients with hyperfluorescent DME than in those with
      minimally fluorescent DME (P = 0.0172). Vitreous levels of VEGF and PEDF were
      related to the retinal thickness at the central fovea (P<0.0001 and P = 0.0469,
      respectively). CONCLUSIONS: Our retrospective study suggests that VEGF and PEDF
      have an independent association with vascular permeability in the eye and on the
      DME, and we recommend that prospective validation of our findings be undertaken
      to confirm these observations.

PMID- 16406544
TI  - Multifocal visual evoked potential analysis of inflammatory or demyelinating
      optic neuritis.
AB  - OBJECTIVE: To determine the sensitivity of multifocal visual evoked potentials
      (mVEP) in optic neuritis of an inflammatory or demyelinating nature. DESIGN:
      Cross-sectional study. PARTICIPANTS: Sixty-four patients participated who had a
      confirmed diagnosis of optic neuritis (ON) (past and acute). Based on the
      McDonald multiple sclerosis (MS) criteria, 25 patients (27 eyes with ON) were
      deemed to have isolated optic neuritis and thus not have MS (i.e., the not-MS
      group), and 19 patients (24 eyes with ON) had a diagnosis of MS (i.e., the MS
      group). The remaining 20 patients (25 eyes with ON) were at a high risk of MS,
      but diagnostic evaluation was equivocal, and thus were classified as the possible
      MS group. A control group of 20 normal patients was enrolled. TESTING: The mVEP
      test was performed using the Accumap. All ON patients had recent magnetic
      resonance imaging scans of the brain and spinal cord. MAIN OUTCOME MEASURES:
      Multifocal visual evoked potentials amplitude and latency values were analyzed
      within each group and were compared with the normal controls. RESULTS: No
      abnormality was recorded on mVEP in the control group. Of all the ON eyes, 74
      (97.3%) were abnormal on mVEP testing. Amplitude values were abnormal in 92.6% of
      not-MS eyes, 92.0% of possible MS eyes, and 100% of those with MS, and latency
      was abnormal in 33.3%, 76.0%, and 100%, respectively. There was a significant
      difference in the mVEP latency z-scores among all ON groups (P<0.01; Kruskal
      Wallis test). Although distribution graphs of latency z-scores in the not-MS and
      MS groups had single peaks and were clearly separate from each other, the latency
      z-score distribution within the possible MS group in postacute patients was
      bimodal, with each peak corresponding to the distribution of the not-MS and MS
      group, respectively. The mVEP latency z-scores had a sensitivity and specificity
      of 100% in detecting patients with ON due to MS when compared with normal
      patients. CONCLUSIONS: The mVEP test is a sensitive and specific tool for
      detecting optic neuritis. There was a significant difference in latency analysis
      findings between patient groups as classified according to the McDonald MS
      criteria. Latency results suggest a role in identifying a patient's risk for
      future MS.

PMID- 16406545
TI  - Retrospective case review of pediatric patients with uveitis treated with
      infliximab.
AB  - PURPOSE: To assess the response and adverse events associated with infliximab
      treatment for refractory, noninfectious pediatric uveitis. DESIGN: Retrospective
      noncomparative case series of pediatric patients with refractory uveitis treated
      with infliximab. PARTICIPANTS: Six patients were identified. Diagnoses of the
      participants included idiopathic uveitis (n = 1), juvenile rheumatoid arthritis
      with uveitis (n = 3), idiopathic retinal vasculitis with uveitis (n = 1), and
      bilateral pars planitis, with vitreitis and papillitis of the left eye (n = 1).
      Uveitis developed in the patients (5 female, 1 male) at a mean age of 9.0 years
      (+/-5.0 years; range, 0.9-14.8 years). All patients had bilateral eye
      involvement. These patients were refractory to or dependent on topical steroids
      (n = 4), oral prednisone (n = 3), or both, and were also refractory to the
      following therapies: methotrexate (n = 6), cyclosporine (n = 3), mycophenolate
      mofetil (n = 3), etanercept (n = 3), and daclizumab (n = 1). INTERVENTION: All
      patients initially received infliximab at doses between 5 and 10 mg/kg at 2- to 4
      week intervals, and then were maintained at 4- to 8-week intervals at doses of 5
      to 18 mg/kg. Mean follow-up time on treatment has been 48.1 weeks (+/-14.9 weeks;
      range, 32-74 weeks). MAIN OUTCOME MEASURES: Primary outcome measures included the
      quantitative measurement of the amount of ocular inflammation in different
      locations within the eye. Patients were monitored for infusion reactions as well
      as other potential side effects. The children's clinical status, complete blood
      counts, and liver function panels were monitored by pediatric rheumatologists
      every 6 weeks. RESULTS: All 6 patients showed reduction in their intraocular
      inflammation after infliximab therapy was initiated. Furthermore, control of
      ocular inflammation was achieved while receiving infliximab therapy. Topical and
      systemic corticosteroids were able to be discontinued in all patients except for
      1 patient, who is currently weaning off prednisone. The only adverse reactions
      seen were the development of vitreous hemorrhage in 1 patient and a case of
      transient upper respiratory infusion reaction. No patient has had to discontinue
      treatment. CONCLUSIONS: Infliximab seems to be an effective agent for the
      treatment of refractory pediatric uveitis without apparent serious toxicity in
      this series of patients.

PMID- 16406546
TI  - Pre-B-cell acute lymphoblastic leukemia presenting as an orbital mass in an 8
      month-old.
AB  - PURPOSE: To present the case of an 8-month-old girl with undiagnosed pre-B-cell
      acute lymphoblastic leukemia (ALL) presenting as an orbital mass. DESIGN:
      Observational case report and literature review. METHODS: Review of clinical
      history, radiologic findings, histology of cervical lymph node and orbital
      biopsies, and follow-up. RESULTS: An 8-month-old girl presented with a 2-week
      history of right-sided tearing, lid swelling, proptosis, and rhinorrhea. A
      computed tomographic scan of the orbits revealed a homogeneous, retrobulbar
      orbital mass eroding into the ethmoid sinuses and nasal cavity, as well as
      cervical lymphadenopathy. Biopsy of the lesion and enlarged lymph node disclosed
      medium-sized, uniform, cytologically atypical lymphocytes in a starry sky
      pattern. Immunohistochemical analysis showed reactivity to antibodies against CD
      10, CD-19, CD-34, and terminal deoxynucleotidyl transferase. Cytogenetic analysis
      of the tumor also revealed a gene rearrangement on chromosome 11q23. Based on
      these findings, the diagnosis of pre-B-cell acute lymphoblastic leukemia was
      made, and systemic as well as intrathecal chemotherapy was instituted, which
      resulted in rapid remission of the leukemia. CONCLUSIONS: The initial
      presentation of ALL as an orbital mass is exceedingly rare. To the best of the
      authors' knowledge, this is the earliest reported case of pre-B-cell ALL
      presenting as an orbital lesion.

PMID- 16406547
TI  - Apolipoprotein E gene and early age-related maculopathy: the Atherosclerosis Risk
      in Communities Study.
AB  - OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene
      and early age-related maculopathy (ARM) in middle-aged persons. DESIGN:
      Population-based cross-sectional study. PARTICIPANTS: Participants from the
      Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 years).
      METHODS: Retinal photography was performed on 1 randomly selected eye, and
      grading for presence of ARM was carried out using a modification of the Wisconsin
      ARM Grading System. Early ARM was defined as the presence of either soft drusen
      alone, retinal pigment epithelial depigmentation alone, or a combination of soft
      drusen with increased retinal pigment and/or depigmentation. DNA extracted from
      blood samples of participants were analyzed for common allelic variants of the
      APOE gene (epsilon2, epsilon3, and epsilon4). MAIN OUTCOME MEASURES: Presence of
      early ARM on retinal photographs. RESULTS: The prevalence of early ARM was
      similar in participants with different APOE genotypes: epsilon2/epsilon2 (5.9%),
      epsilon2/epsilon3 (5.2%), epsilon2/epsilon4 (3.2%), epsilon3/epsilon3 (5.2%),
      epsilon3/epsilon4 (4.9%), and epsilon4/epsilon4 (4.1%). After controlling for
      age, gender, race, cigarette smoking, and other factors, early ARM was not
      associated with APOE genotypes, with an odds ratio (OR) of 1.35 (95% confidence
      interval [CI], 0.54-3.38) for epsilon2/epsilon2 genotype, an OR of 1.06 (95% CI,
      0.80-1.40) for epsilon2/epsilon3 genotype, an OR of 0.63 (95% CI, 0.32-1.24) for
      epsilon2/epsilon4 genotype, an OR of 0.99 (95% CI, 0.80-1.24) for
      epsilon3/epsilon4 genotype, and an OR of 0.88 (95% CI, 0.47-1.63) for
      epsilon4/epsilon4 genotype, as compared with epsilon3/epsilon3 genotype
      (reference). No associations were found for specific early ARM signs or in
      analyses stratified by age, gender, race, or cigarette smoking status.
      CONCLUSIONS: These data provide no evidence of a strong association between the
      APOE gene and early ARM in middle-aged persons. This suggests that APOE is not
      likely a major determinant of the early stages of ARM in younger people. However,
      our study does not exclude the possibility of a weaker association or that APOE
      may influence only the development of late ARM in older populations, as reported
      in other studies.

PMID- 16406548
TI  - Radioactive sputter cathodes for 32P plasma-based ion implantation.
AB  - The development of clinical treatments involving the use of beta-emitting
      millimetric and sub-millimetric devices has been a continuing trend in nuclear
      medicine. Implanted a few nanometers below the surface of endovascular implants,
      seeds or beads, beta-emitting radioisotopes can be used in a variety of
      biomedical applications. Recently, new technologies have emerged to enable the
      rapid and efficient activation of such devices. A pulsed, coaxial electron
      cyclotron resonance plasma reactor was designed and tested to demonstrate the
      feasibility of plasma-based radioactive ion implantation (PBRII). It has been
      shown that such plasma reactors allow for the implantation of radioisotopes (32P)
      into biomedical devices with higher efficiencies than those obtained with
      conventional ion beams. Fragments containing radioactive atoms are produced in
      the implanter by means of a negatively biased solid sputter cathode that is
      inserted into an argon plasma. Dilute orthophosphoric acid solutions (H3(32)PO4)
      are used for the fabrication of flat sputter targets, since they offer a high
      radioisotope content. However, the aggregation of the radioactive solute into
      highly hygroscopic ring-like deposits rather than flat, thin radioactive films is
      observed on certain substrates. This article describes the effect of this
      nonuniform distribution of the radioisotopes on the efficiency of PBRII, and
      presents a technique which enables a better distribution of 32P by coating the
      substrates with iron. The iron coating is shown to enable optimal radioisotope
      sputtering rates, which are essential in 32P-PBRII for the efficient activation
      of millimetric biomedical devices such as stents or coils.

PMID- 16406549
TI  - Regulation of neurotensin receptor function by the arachidonic acid-lipoxygenase
      pathway in prostate cancer PC3 cells.
AB  - Neurotensin (NT) elevates leukotriene levels in animals and stimulates 5-HETE
      formation in prostate cancer PC3 cells. PC3 cell growth is stimulated by NT and
      inhibited by lipoxygenase (LOX) blockers. This led us to test LOX blockers (NDGA,
      MK886, ETYA, Rev5901, AA861 and others) for effects on NT binding and signaling.
      LOX blockers dramatically enhanced 125I-neurotensin binding to NT receptor NTR1
      in PC3 cells, whereas they inhibited NT-induced inositol phosphate formation.
      These effects were indirect (binding to isolated membranes was unaffected),
      receptor-specific (binding to beta2-adrenergic, V1a-vasopressin, EGF and bombesin
      receptor was unaffected) and pathway-specific (cyclooxygenase inhibitors were
      inactive). NT receptor affinity was increased but receptor number and %
      internalization were unchanged. Also supporting the involvement of arachidonic
      acid metabolism in NTR1 regulation was the finding that inhibitors of PLA2 and
      DAG lipase enhanced NT binding. These findings suggest that NTR1 is regulated by
      specific feedback mechanism(s) involving lipid peroxidation and/or LOX-dependent
      processes.

PMID- 16406552
TI  - PUVA treatment of the nasal cavity improves the clinical symptoms of allergic
      rhinitis and inhibits the immediate-type hypersensitivity reaction in the skin.
AB  - We earlier reported that intranasal irradiation with the 308 nm xenon chloride
      (XeCl) ultraviolet-B laser and irradiation with a combination of ultraviolet-B
      (UVB), ultraviolet-A (UVA) and visible light (VIS) is highly effective in the
      treatment of allergic rhinitis and inhibit the immediate-type hypersensitivity
      reaction in the skin. Since photochemotherapy with 8-methoxypsoralen (8-MOP) plus
      UVA light (PUVA) is widely used in the treatment of different inflammatory skin
      disorders due to its immunosuppressive effect, in the present study we
      investigated the efficacy of intranasal PUVA treatment in allergic rhinitis and
      the effect of PUVA treatment on the skin prick test (SPT) reaction. An open study
      was performed in 17 patients with hay fever. Intranasal PUVA therapy was given
      four times weekly for 3 weeks. The treatment was started with a fluence of 0.5x
      of the individual minimal phototoxic dose (MPD) and the dosages were gradually
      increased. Evaluation was based on the symptom scores. The effect of PUVA
      treatment on the allergen-induced wheal formation was also studied in the SPT.
      PUVA treatment of the nasal cavity significantly decreased the nasal symptoms of
      the patients with allergic rhinitis. Treatment of the skin with PUVA also
      significantly suppressed the allergen-induced wheal formation in the SPT
      reaction. These data suggest that intranasal PUVA phototherapy is also an
      effective modality in the treatment of allergic rhinitis.

PMID- 16406550
TI  - Structures, spectra, and DNA-binding properties of mixed ligand copper(II)
      complexes of iminodiacetic acid: the novel role of diimine co-ligands on DNA
      conformation and hydrolytic and oxidative double strand DNA cleavage.
AB  - The coordination geometry around copper(II) in [Cu(imda)(phen)(H2O)] (1) (H2imda
      = iminodiacetic acid, phen = 1,10-phenanthroline) is described as distorted
      octahedral while those in [Cu(imda)(5,6-dmp)] (2) (5,6-dmp = 5,6-dimethyl-1,10
      phenanthroline) and [Cu(imda)(dpq)] (3) (dpq = dipyrido-[3,2-d:2',3'-f]
      quinoxaline) as trigonal bipyramidal distorted square-based pyramidal with the
      imda anion facially coordinated to copper(II). Absorption spectral (Kb: 1, 0.60+/
      0.04x10(3); 2, 3.9+/-0.3x10(3); 3, 1.7+/-0.5x10(4) M(-1)) and thermal
      denaturation studies (deltaTm: 1, 5.70+/-0.05; 2, 5.5+/-10; 3, 10.6+/-10 degrees
      C) and viscosity measurements indicate that 3 interacts with calf thymus DNA more
      strongly than 1 and 2. The relative viscosities of DNA bound to 1 and 3 increase
      while that of DNA bound to 2 decreases indicating formation of kinks or bends
      and/or conversion of B to A conformation as revealed by the decrease in intensity
      of the helicity band in the circular dichroism spectrum of DNA. While 1 and 3 are
      bound to DNA through partial intercalation, respectively, of phen ring and the
      extended planar ring of dpq with DNA base stack, the complex 2 is involved in
      groove binding. All the complexes show cleavage of pBR322 supercoiled DNA in the
      presence of ascorbic acid with the cleavage efficiency varying in the order 3 > 1
      > 2. The highest oxidative DNA cleavage of dpq complex is ascribed to its highest
      Cu(II)/Cu(I) redox potential. Oxidative cleavage studies using distamycin reveal
      minor groove binding for the dpq complex but a major groove binding for the phen
      and 5,6-dmp complexes. Also, all the complexes show hydrolytic DNA cleavage
      activity in the absence of light or a reducing agent with cleavage efficiency
      varying in the order 1 > 3 > 2.

PMID- 16406553
TI  - Three new asexual arthroconidial yeasts, Geotrichum carabidarum sp. nov.,
      Geotrichum histeridarum sp. nov., and Geotrichum cucujoidarum sp. nov., isolated
      from the gut of insects.
AB  - Twenty arthroconidial yeasts were isolated from the digestive tract of basidiome
      feeding beetles and lepidopteran larvae. All of the yeasts reproduced only
      asexually by arthroconidia and some by endo- or blastoconidia as well. Based on
      the comparisons of sequences in ribosomal RNA genes and other taxonomic
      characteristics, the yeasts were identified as three unknown Geotrichum species.
      The three new species are described as Geotrichum carabidarum (NRRL Y-27727T), G.
      histeridarum (NRRL Y-27729T), and G. cucujoidarum (NRRL Y-27731T). Phylogenetic
      analyses from ribosomal DNA sequences showed that members of the genus Geotrichum
      and related arthroconidial yeast taxa were divided into two major clades: (1)
      Dipodascus and Galactomyces with Geotrichum anamorphs including all the new
      species; and (2) Magnusiomyces with Saprochaete anamorphs. G. cucujoidarum formed
      a subclade with G. fermentans and Geotrichum sp. Y-5419, while the two closely
      related species, G. carabidarum and G. histeridarum, represent a new basal
      subclade in the clade of Geotrichum and its teleomorphs.

PMID- 16406551
TI  - Changes in the energy distribution in mutant thylakoid membranes of pea with
      modified pigment content. II. Changes due to magnesium ions concentration.
AB  - Low-temperature (77K) steady-state chlorophyll fluorescence emission spectra,
      room temperature fluorescence and light scattering of thylakoid membranes
      isolated from pea mutants were studied as a function of Mg2+ concentration. The
      mutants have modified pigment content and altered structural organization of the
      pigment-protein complexes, distinct surface electric properties and functions.
      The analysis of the 77K emission spectra revealed that Mg2+-depletion of the
      medium caused not only an increased energy flow toward photosystem I in all
      investigated membranes but also changes in the quenching of the fluorescence,
      most probably by internal conversion. The results indicated that the
      macroorganization of the photosynthetic apparatus of mutants at supramolecular
      level (distribution and segregation of two photosystems in thylakoid membranes)
      and at supermolecular level (stacking of photosystem II supercomplexes) required
      different Mg ion concentrations. The data confirmed that the segregation of
      photosystems and the stacking of thylakoid membranes are two distinct phenomena
      and elucidated some features of their mechanisms. The segregation is initiated by
      changes in the lateral microorganization of light harvesting complexes II, their
      migration (repulsion from photosystem I) and subsequent separation of the two
      photosystems. Most likely 3D aggregation and formation of macrodomains,
      containing only photosystem II antenna complexes, play a certain precursory role
      for the increasing degree of the membrane stacking and the energy coupling
      between the light harvesting complexes II and the core complexes of photosystem
      II in the frame of photosystem II supercomplexes.

PMID- 16406554
TI  - Presence of anti-platelet IgM and IgG antibodies in dogs naturally infected by
      Leishmania infantum.
AB  - Thirty-three dogs, naturally infected by Leishmania infantum, were enrolled in
      the study and were classified as oligo-symptomatic (n. 15) and symptomatic or
      markedly symptomatic (n. 18). A control group was 10 healthy dogs. A
      haematological profile was obtained and the dogs serum was employed to assess the
      presence of platelet binding IgM and IgG antibodies (PBIgM, PBIgG) using flow
      cytometry. FITC labelled goat anti-dog IgM or IgG were used to detect PBIgM and
      PBIgG. Samples with a mean fluorescence intensity (MFI) that was 100 channels
      higher on a log scale for more than 30% of the platelets than seen in negative
      control platelets from a healthy dog were considered positive for the presence of
      anti-platelet antibodies (PBIg). Twenty-one (63.3%) dogs revealed the presence of
      PBIg. Six of them were oligo-symptomatic while 15 showed moderate or severe
      clinical signs of illness. All the dogs with PBIg showed the presence of PBIgM,
      with nine animals showing both PBIgM and PBIgG. Nine of 18 symptomatic or
      markedly symptomatic dogs showed thrombocytopenia, while normal platelet counts
      were observed in all oligo-symptomatic animals. Eight of 9 thrombocytopenic
      animals showed the presence of PBIgM, while six of them showed PBIgG. One
      thrombocytopenic dog was negative for PBIg. This study is the first report
      documenting the presence of PBIg in natural canine leishmaniasis implying a
      pathogenic association between thrombocytopenia and the presence of antibody
      against platelet membrane.

PMID- 16406555
TI  - The combined effects of anti-TNFalpha antibody and IL-1 receptor antagonist in
      human rheumatoid arthritis synovial membrane.
AB  - TNFalpha and IL-1 are the pivotal cytokines involved in rheumatoid arthritis
      (RA). More recently, the biological therapy targeting TNFalpha or IL-1 has been
      impressively effective for many RA patients, however, it remains insufficient in
      some patients. In the present study, we examined the combined effects of two
      agents against TNFalpha and IL-1 in human RA synovial membrane. Synovial explants
      (an ex vivo model) and synovial fibroblasts (an in vitro model) were prepared
      from 11 RA patients, and then anti-TNFalpha antibody (Anti-TNFalpha) and IL-1
      receptor antagonist (IL-1Ra), either alone or in combination, were added to the
      synovial explants and fibroblasts. IL-6 and MMP-3 production were measured after
      incubation. As a result, their production significantly decreased by the
      combination of agents compared with the control group in both the synovial
      explants and fibroblasts. The efficacy of this combination was also observed for
      IL-6 production compared with each agent alone in the synovial explants, and for
      IL-6 and MMP-3 production compared with each agent alone in the synovial
      fibroblasts. Therefore, the combination of Anti-TNFalpha and IL-1Ra appears more
      beneficial in synovial membrane, particularly when compared with a single agent
      alone.

PMID- 16406556
TI  - Alteration pattern of tear cytokines during the course of a day: diurnal rhythm
      analyzed by multicytokine assay.
AB  - Our aim was to study the alteration pattern and interaction of inflammatory tear
      cytokines during the course of a day. Using a prospective, experimental design,
      tears were collected from 28 healthy volunteers with normal eyes during the
      period from April 2004 to March 2005. Tears (10 microl) were collected by
      capillary outflow from each eye at 9:00, 12:00, 16:00, 21:00, and 24:00 h. The
      concentrations of inflammatory cytokines, IL-1beta, IL-6, IL-8, IL-10, IL-12p70,
      and TNF-alpha were measured using cytometric bead arrays. Although the
      concentration of tear cytokines varied widely among eyes, the amount of cytokine
      had a specific alteration pattern in each eye during the course of a day. IL
      1beta, IL-6, IL-10, IL-12p70, and TNF-alpha showed slight increases in the
      morning and the late evening. IL-8 remained low throughout the day. The
      alteration pattern of IL-8 was significantly different from those of TNF-alpha
      and IL-12p70 (P<0.01). The ratio of each pro-inflammatory cytokine to anti
      inflammatory cytokine IL-10 did not significantly change throughout the day. The
      amount of tear cytokines changed during daytime with a specific pattern. This
      diurnal rhythm may influence symptoms of ocular surface diseases during the
      course of a day.

PMID- 16406557
TI  - Molecular characterization of woodchuck interleukin 15 (wIL-15) and detection of
      its expression in liver samples of woodchucks infected with woodchuck hepatitis
      virus (WHV).
AB  - Interleukin 15 (IL-15) is a member of the four-helix bundle cytokine family and
      has T cell growth factor activity. IL-15 plays a unique role in both innate and
      adaptive immune cell homeostasis, particularly for the development of NK cells
      and CD8+memory cells. It may be useful for stimulation of specific immune
      responses in chronic viral infection such as hepatitis B virus infection. The
      woodchuck model is an informative animal model for studies on hepadnavirus
      infection and therapeutic interventions. Here, the complete coding sequence of
      woodchuck IL-15 (wIL-15) was cloned and sequenced. wIL-15 shows a high homology
      (>70%) to its counterparts of other mammalian species. His-tagged recombinant wIL
      15 protein was expressed and purified and showed the ability to promote the
      proliferation of activated mouse splenocytes and woodchuck peripheral blood
      lymphocytes. Further, examination of mRNA amounts in liver samples of woodchucks
      by semi-quantitative RT-PCR showed a slightly increased expression of wIL-15 in
      woodchuck livers during chronic woodchuck hepatitis virus infection. This
      available information will provide a basis for further studies on the function of
      IL-15 in the context of acute and chronic hepadnavirus infection and its
      potential therapeutic use for chronic hepatitis B virus infection in the
      woodchuck model.

PMID- 16406558
TI  - Chemokine production and pattern recognition receptor (PRR) expression in whole
      blood stimulated with pathogen-associated molecular patterns (PAMPs).
AB  - Recognition of conserved bacterial structures called pathogen-associated
      molecular patterns (PAMPs) by pattern recognition receptors (PRRs), may lead to
      induction of a variety of "early immediate genes" such as chemokines. In the
      current study, we have in an ex vivo whole blood model studied the induction of
      the chemokines MIP-1alpha, MCP-1 and IL-8 by various PAMPs. The rate of
      appearance of Escherichia coli-Lipopolysaccharide (LPS) induced chemokines
      differed. The production of MIP-1alpha and IL-8 was after 1 h of stimulation
      significantly higher when compared to unstimulated whole blood, whereas MCP-1 was
      not significantly elevated until after 3 h. At peak levels the MIP-1alpha
      concentration induced by E. coli-LPS was 3-5-fold higher than MCP-1 and IL-8. By
      specific cell depletion, we demonstrated that all three chemokines were mainly
      produced by monocytes. However, the mRNA results showed that IL-8 was induced in
      both monocytes and granulocytes. The production of all three chemokines, induced
      by the E. coli-LPS and Neisseria meningitidis-LPS, was significantly inhibited by
      antibodies against CD14 and TLR4, implying these receptors to be of importance
      for the effects of LPS in whole blood. The chemokine production induced by
      lipoteichoic acid (LTA) and non-mannose-capped lipoarabinomannan (AraLAM) was,
      however, less efficiently blocked by antibodies against CD14 and TLR2. E. coli
      LPS and LTA induced a dose-dependent increase of CD14, TLR2 and TLR4 expression
      on monocytes in whole blood. These data show that PAMPs may induce chemokine
      production in whole blood and that antibodies against PRRs inhibit the production
      to different extent.

PMID- 16406559
TI  - Immunohistochemical approach to the pathogenesis of bovine spongiform
      encephalopathy in its early stages.
AB  - An immunohistochemical and histochemical study was carried out on the brains of
      nine cases of BSE-diagnosed cattle as part of the surveillance plan in Catalonia,
      Spain. The animals had no clinical symptoms reported and were thus at early
      stages of the disease. The first part of the study consisted of a
      characterization of PrP(BSE) deposits throughout the encephalon. The behaviour of
      the different immuno-labelling patterns was analysed and tropism of some patterns
      towards certain brain areas was described. This tropism is principally directed
      to the brain stem region; however, an association of the stellate pattern was
      found with areas where PrP(BSE) is deposited less abundantly, such as the
      cerebral cortex. Secondly, distinct pathogenesis mechanisms that take place in
      the early stages of BSE, which would include these cases were investigated. This
      study describes the glial response to the presence of PrP(BSE) (using antibodies
      against astrocytic glial fibrillary acidic protein and lectin from Griffonia
      simplicifolia to identify microglia), the presence of mild oxidative stress
      phenomena (antibodies against metallothioneins I and II and against nitrated
      aminoacidic residues: nitrotyrosine), the apparent absence of apoptotic cellular
      death (cleaved caspase 3) and the preservation of synaptic proteins synaptophysin
      and small synaptosome-associated 25 kDa protein immuno-labelling. Finally, no
      alteration of the extra-cellular matrix was detected with the use of Wisteria
      floribunda agglutinin, a marker for perineuronal nets.

PMID- 16406560
TI  - Comparison between two methods for estimating pneumothorax size from chest X
      rays.
AB  - AIM: To compare the estimated size of spontaneous pneumothoraces using the
      established Rhea inter-pleural distances method with the CT-derived Collins
      method. METHOD: Adult patients with spontaneous pneumothorax treated
      conservatively were identified from the ED databases. X-rays were reviewed
      independently by two researchers and measured according to the methods described
      by Rhea and Collins. Estimates of size derived by the two methods were compared
      using bias plot analysis techniques. RESULTS: A total of 156 X-rays in 57
      patients were identified. A total of 82% were male with a median age of 22 years.
      Pneumothoraces varied in size from 4% to 88%. The average difference between
      methods was 4% (Collins method estimating larger size) with 95% limits of
      agreement -3.8% to 11.7%. Agreement was very close for small pneumothoraces but
      deteriorated with increasing pneumothorax size (Collins methods estimated larger
      pneumothorax size). CONCLUSION: The Rhea method for estimating pneumothorax size
      is acceptably accurate for smaller pneumothoraces but may significantly under
      estimate the size of larger pneumothoraces.

PMID- 16406561
TI  - A novel approach for identification and characterization of glycoproteins using a
      hybrid linear ion trap/FT-ICR mass spectrometer.
AB  - Combining source collision-induced dissociation (CID) and tandem mass spectral
      acquisition in a pseudo-MS(3) experiment using a linear ion trap results in a
      highly selective and sensitive approach to identifying glycopeptide elution from
      a protein digest. The increased sensitivity is partially attributed to the
      nonselective nature of source CID, which allows simultaneous activation of all
      charge states and coeluting glycoforms generating greater ion abundance for the
      mass-to-charge (m/z) 204 and/or 366 oxonium ions. Unlike source CID alone, a
      pseudo-MS(3) approach adds selectivity while improving sensitivity by eliminating
      chemical noise during the tandem mass spectral acquisition of the oxonium ions in
      the linear ion trap. Performing the experiments in the hybrid linear ion
      trap/Fourier transform-ion cyclotron resonance (FT-ICR) enables subsequent high
      resolution/high-mass accuracy full-scan mass spectra (MS) and parallel
      acquisition of MS/MS in the linear ion trap to be completed in 2 s directly
      following the pseudo-MS(3) scan to collate identification and characterization of
      glycopeptides in one experimental scan cycle. Analysis of bovine fetuin digest
      using the combined pseudo-MS(3), high-resolution MS, and data-dependent MS/MS
      events resulted in identification of four N-linked and two O-linked glycopeptides
      without enzymatic cleavage of the sugar moiety or release of the sialic acids
      before analysis. In addition, over 95% of the total protein sequence was
      identified in one analytical run.

PMID- 16406562
TI  - Some guidelines for the analysis of genomic DNA by PCR-LC-ESI-MS.
AB  - Ion-pair reversed-phase high-performance liquid chromatography online hyphenated
      to electrospray ionization mass spectrometry (ICEMS) represents an efficient
      method for the characterization of nucleic acids amplified by polymerase chain
      reaction (PCR). Since sample preparation is limited to PCR, the optimization of
      its solution conditions is of utmost importance for efficient mass spectrometric
      detection. The compatibility of a number of different commercially available PCR
      components including DNA polymerases, deoxynucleotide triphosphates, bovine serum
      albumin, enhancer, and ionic buffers was evaluated. These experiments revealed
      that higher concentration of enhancer and detergents such as Tween-20 or Nonidet
      P-40 impairs the mass spectrometric detection of nucleic acids and should be
      avoided within the PCR mixture. The optimized analytical platform was applied to
      the characterization of PCR products covering parts of the first hypervariable
      region of the noncoding mitochondrial control region. Truncated amplicons were
      detected attributable to the use of low quality primers. Furthermore, due to the
      proofreading activity of the applied polymerase system, mismatches between the
      primer and the target sequence located at the last or the second last base at the
      3'-end of primers were corrected and detected within the corresponding amplicons.

PMID- 16406563
TI  - The association of sub-clinical paratuberculosis with the fertility of Greek
      dairy ewes and goats varies with parity.
AB  - Our cross-sectional study investigated the association of sub-clinical
      Mycobacterium avium subsp. paratuberculosis (MAP) infection with failing to
      produce a live offspring the season of lambing/kidding (November 2001 to January
      2002) before testing (in April-May 2002), in four dairy-sheep and/or goat flocks
      in Greece (369 animals >or=1.5-year-old). From each selected animal 10 ml of
      blood and 10 g of feces from the rectum were obtained. The harvested sera were
      tested for antibodies to MAP with a commercial ELISA test kit; the feces were
      cultured on Herrold's egg-yolk medium supplemented with mycobactin J and
      antibiotics. An animal was considered sub-clinically infected when found either
      seropositive or culture positive. The true prevalence of sub-clinically infected
      animals, adjusted for the sensitivity and specificity of the parallel testing,
      was 14% (0.1-28%) and 35.9% (9.2-62.7%) in sheep and goats, respectively. The
      association of fertility of sheep and goats with sub-clinical paratuberculosis
      was investigated in random-effects logistic models. Sub-clinically infected
      animals (compared to uninfected) had OR for live offspring the previous year of
      5.4 for parity <4, OR=0.05 for parity >6, and a non-significant OR for the middle
      parity category.

PMID- 16406564
TI  - Forest products decomposition in municipal solid waste landfills.
AB  - Cellulose and hemicellulose are present in paper and wood products and are the
      dominant biodegradable polymers in municipal waste. While their conversion to
      methane in landfills is well documented, there is little information on the rate
      and extent of decomposition of individual waste components, particularly under
      field conditions. Such information is important for the landfill carbon balance
      as methane is a greenhouse gas that may be recovered and converted to a CO(2)
      neutral source of energy, while non-degraded cellulose and hemicellulose are
      sequestered. This paper presents a critical review of research on the
      decomposition of cellulosic wastes in landfills and identifies additional work
      that is needed to quantify the ultimate extent of decomposition of individual
      waste components. Cellulose to lignin ratios as low as 0.01-0.02 have been
      measured for well decomposed refuse, with corresponding lignin concentrations of
      over 80% due to the depletion of cellulose and resulting enrichment of lignin.
      Only a few studies have even tried to address the decomposition of specific waste
      components at field-scale. Long-term controlled field experiments with supporting
      laboratory work will be required to measure the ultimate extent of decomposition
      of individual waste components.

PMID- 16406566
TI  - Modification of the fluorescein diacetate assay for screening of antifungal
      agents against Candida albicans: comparison with the NCCLS methods.
AB  - A modified fluorescein diacetate (FDA) assay has been compared with standard
      NCCLS broth macrodilution and broth microdilution methods for the detection of
      antifungal activity. The FDA assay was performed in a medium containing
      bacteriological peptone, NaCl, yeast extract and glucose (0.2%, 0.1%, 0.1% and 1%
      w/v, respectively) and buffered with 10 mM BES buffer. The MICs of amphotericin
      B, fluconazole, miconazole and flucytosine (representing three major classes of
      antifungal agents) obtained by the three methods were compared. The results
      obtained with the FDA assays correlated well with the NCCLS macrodilution method
      for MICs of amphotericin B, miconazole and fluconazole, but not for flucytosine.
      However, the MIC values of flucytosine obtained with the FDA assay were well
      within the quality control range for the two reference strains recommended by the
      NCCLS. The FDA assay described is an attractive alternative to the NCCLS methods
      for screening for antifungal agents, with the added advantage of objectivity of
      fluorescence measurement.

PMID- 16406567
TI  - Strategy of macromolecular grafting onto a gold substrate dedicated to protein
      protein interaction measurements.
AB  - Many biotechnology applications use proteins immobilized on surface. For
      biosensor, the sensing layer is a key component interfacing the transducer and
      the sample. Strategies employed to activate the bidimensional surface act
      directly on the performance of the biosensor. In this paper we propose a novel
      strategy for engineered proteins self-assembly. Our original supramolecular
      structure allows a direct and fast covalent attachment of proteins onto bare gold
      substrate through a homobifunctional cross-linker, 1,4-di-([2'
      pyridyldithio]propionamido)butane (DPDPB). In this work, engineered proteins and
      linker-protein complexes were synthesized and characterized by gel
      electrophoresis, chromatography and spectroscopy experiments. Macromolecular
      construction "DPDPB-GST tag-GEC1 protein" was conceived in order to guarantee a
      2D architecture enhancing the capabilities of the target (tubulin) to recognize
      its partner (GEC1). Surface plasmon resonance measurements clearly showed
      potential of this particular self-assembled protein layer compared to a
      commercial immunosensor interface. At the concentrations tested, the recognition
      process occurs between tubulin and the immobilized GEC1; moreover enhanced
      binding was obtained with the home-made 2D sensing layer more than with 3D
      carboxymethyl dextran matrix.

PMID- 16406568
TI  - Quartz crystal microbalance bioaffinity sensor for rapid identification of
      glycosyldisulfide lectin inhibitors from a dynamic combinatorial library.
AB  - Carbohydrate-lectin interactions were probed with dynamic combinatorial
      libraries, using the plant lectin Concanavalin A as target species. The dynamic
      combinatorial libraries were generated from a pool of thiol components through
      reversible thiol-disulfide interchange, and screened using a simple and efficient
      method based on a quartz crystal microbalance setup. It was found that dimers
      based on 1-thio- and 6-thio-mannose analogues were the most active inhibitors.
      Furthermore, the results clearly show that the 6-thio-mannose possess unique
      characteristics compared to its oxygen-containing counterpart.

PMID- 16406569
TI  - Effects of geometry on transmission and sensing potential of tapered fiber
      sensors.
AB  - Geometry of tapered fiber sensors critically affects the response of an
      evanescent field sensor to cell suspensions. Single-mode fibers (nominally at
      1300 nm) were tapered to symmetric or asymmetric tapers with diameters in the
      range of 3-20 microm, and overall lengths of 1-7 mm. Their transmission
      characteristics in air, water and in the presence of Escherichia coli (JM101
      strain) at concentrations of 100, 1000, 7000 and 7 million cells/mL were measured
      in the 400-800 nm range and gave rich spectral data that lead to the following
      conclusions. (1) No change in transmission was observed due to E. coli with
      tapers that showed no relative change in transmission in water compared to air.
      (2) Tapers that exhibited a significant difference in transmission in water
      compared to air gave weak response to the presence of the E. coli. Of these,
      tapers with low waist diameters (6 microm) showed sensitivity to E. coli at 7000
      cells/mL and higher concentration. (3) Tapers that showed modest difference in
      water transmission compared to air, and those that had small waist diameters gave
      excellent response to E. coli at 100-7000 cells/mL. In addition, mathematical
      modeling showed that: (1) at low wavelength (470 nm) and small waist diameter (6
      microm), transmission with water in the waist region is higher than in air. (2)
      Small changes in waist diameter (approximately 0.05 microm) can cause larger
      changes in transmission at 470 nm than at 550 nm at waist diameter of 6 microm.
      (3) For the same overall geometry, a 5.5 microm diameter taper showed larger
      refractive index sensitivity compared to a 6.25 microm taper at 470 nm.

PMID- 16406570
TI  - Lectins and microparticles for enhanced oral vaccination.
AB  - Oral administration is an attractive means of vaccination since it alleviates the
      need for injection and trained personnel. Furthermore, effective oral vaccination
      induces immune responses locally in the gastrointestinal tract, the site of
      colonisation and infection by many pathogens. However, since most proteins and
      peptides are degraded in the gut, do not interact specifically with the
      epithelium, or induce strong immune responses, this route of delivery is
      generally inefficient. Two of the most promising potential approaches are the use
      of lectins to target vaccines to the epithelium and the association of vaccines
      with biodegradable microparticles. This paper describes methods to assess the
      stability of vaccines and targeting molecules in the gastrointestinal tract,
      interaction with the mucosa, uptake into internal organs and induction of mucosal
      antibody responses.

PMID- 16406571
TI  - Translation of an experimental oral vaccine formulation into a commercial
      product.
AB  - An effective experimental vaccine may fail to become a therapeutic reality for a
      number of scientific, regulatory or commercial reasons. In this review, we share
      some of our personal experiences as University-based researchers and provide an
      account of some of the problems that we have encountered during preliminary scale
      up and assessment of an oral influenza vaccine formulation. Many of the problems
      we have faced have been non-scientific and related to identifying project-funding
      sources, finding suitable contract manufacturing companies that are GMP
      compliant, and protecting intellectual property generated from the scientific
      studies. The review is intended as a practical guide that will allow other
      researchers to adopt effective strategies to permit the translation of an
      effective experimental formulation to a viable commercial product.

PMID- 16406572
TI  - A light-emitting diode light source for imaging of neural activities with voltage
      sensitive dyes.
AB  - We tested the possibility of using a high-power monochromatic InGaN light
      emitting diode (LED) as an excitation light source for real-time optical imaging
      using the voltage-sensitive dye RH-795. Driven with a custom-designed, non
      feedback-controlled constant-current circuit, the LED generated stable light with
      rapid on/off. The LED was comparable with commonly used halogen lamps in exciting
      RH-795. Acoustically evoked responses in the auditory cortex recorded with the
      two light sources were highly similar. Our results thus suggest that a high-power
      LED can be successfully used as an excitation light source for voltage-sensitive
      dyes, without the need of optical filters and shutters.

PMID- 16406573
TI  - Automated purification of recombinant proteins: combining high-throughput with
      high yield.
AB  - Protein crystallography, mapping protein interactions, and other functional
      genomic approaches require purifying many different proteins, each of sufficient
      yield and homogeneity, for subsequent high-throughput applications. To fill this
      requirement efficiently, there is a need to develop robust, automated, high
      throughput protein expression, and purification processes. We developed and
      compared two alternative workflows for automated purification of recombinant
      proteins based on expression of bacterial genes in Escherichia coli (E. coli).
      The first is a filtration separation protocol in which proteins of interest are
      expressed in a large volume, 800 ml of E. coli cultures, then isolated by
      filtration purification using Ni-NTA-Agarose (Qiagen). The second is a smaller
      scale magnetic separation method in which proteins of interest are expressed in a
      small volume, 25 ml, of E. coli cultures then isolated using a 96-well
      purification system with MagneHis Ni2+ Agarose (Promega). Both workflows provided
      comparable average yields of proteins, about 8 microg of purified protein per
      optical density unit of bacterial culture measured at 600 nm. We discuss
      advantages and limitations of these automated workflows, which can provide
      proteins with more than 90% purity and yields in the range of 100 microg to 45 mg
      per purification run, as well as strategies for optimizing these protocols.

PMID- 16406574
TI  - Caring for survivors of childhood cancers: the size of the problem.
AB  - Many survivors of childhood cancer have significant health problems due to their
      illness or treatment. This population-based study examines the number of long
      term survivors, their disabilities and consequent long-term care needs. Survival
      rates for children diagnosed with cancer between 1960 and 1999 in the West
      Midlands, United Kingdom (UK), were used to estimate future long-term survivor
      numbers. Treatment and late effects data on a cohort of patients surviving for
      more than 5 years were used to consider continuing care needs. Between the 1960s
      and 1990s, 5-year survival increased from 23% to 70%. There were 98 5-year
      survivors in 1970, and numbers may exceed 2,100 by the end of 2005. Most (at
      least 61%) survivors in the West Midlands Region have one or more chronic medical
      problems and may require multidisciplinary care. We conclude that, in order to
      determine how to provide cost-effective care for this increasing population,
      protocol delivered management with audit is needed.

PMID- 16406575
TI  - A genomic explanation connecting "Mediterranean diet", olive oil and cancer:
      oleic acid, the main monounsaturated fatty acid of olive oil, induces formation
      of inhibitory "PEA3 transcription factor-PEA3 DNA binding site" complexes at the
      Her-2/neu (erbB-2) oncogene promoter in breast, ovarian and stomach cancer cells.
AB  - Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating
      evidence suggests that it may have a potential role in lowering risk of several
      cancers. We recently hypothesized that the anti-cancer actions of olive oil may
      relate to its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) content
      to specifically regulate oncogenes. In this study, transient transfection
      experiments with human Her-2/neu promoter-driven luciferase gene established the
      ability of OA to specifically repress the transcriptional activity of Her-2/neu
      gene. Gene repression was seen in tumour-derived cell lines with Her-2/neu gene
      amplification and overexpression, including SK-Br3 (56% reduction), SK-OV3 (75%
      reduction) and NCI-N87 (55% reduction) breast, ovarian and stomach cancer cell
      lines, respectively. Also marginal decreases in promoter activity were observed
      in cancer cells expressing physiological levels of Her-2/neu (20% reduction in
      MCF-7 breast cancer cells). Remarkably, OA treatment in Her-2/neu-overexpressing
      cancer cells was found to induce up-regulation of the Ets protein polyomavirus
      enhancer activator 3 (PEA3), a transcriptional repressor of Her-2/neu promoter.
      Also, an intact PEA3 DNA-binding-site at endogenous Her-2/neu gene promoter was
      essential for OA-induced repression of this gene. Moreover, OA treatment failed
      to decrease Her-2/neu protein levels in MCF-7/Her2-18 transfectants, which stably
      express full-length human Her-2/neu cDNA controlled by a SV40 viral promoter. OA
      induced transcriptional repression of Her-2/neu through the action of PEA3
      protein at the promoter level may represent a novel mechanism linking
      "Mediterranean diet" and cancer.

PMID- 16406576
TI  - Phase I clinical and pharmacological evaluation of the multi-tyrosine kinase
      inhibitor SU006668 by chronic oral dosing.
AB  - SU006668, an oral inhibitor of vascular endothelial growth factor receptor
      (VEGFR), platelet-derived growth factor receptor (PDGFR) and fibroblast growth
      factor receptor (FGFR), was administered in fed conditions to 24 patients with
      advanced solid cancer at 100, 200 and 300 mg/m(2) b.i.d. Dose escalation was
      discontinued because the maximum tolerated dose was defined at 400 mg/m(2) b.i.d
      in a concomitant trial. The drug was generally well tolerated although two
      patients presented possibly drug-related dose-limiting toxicities (pericardial
      effusion and thrombocytopenia). SU006668 had a non-linear pharmacokinetic profile
      characterized by AUC and Cmax decreasing from day 1 to day 28 in all patients at
      all tested doses; a lower apparent bioavailability on day 28 compared to day 1;
      and a significant concomitant increase of the urinary metabolites. These findings
      are in agreement with the presence of saturable absorption and metabolic
      induction. The peculiar pharmacokinetics and >99% protein binding discouraged
      further clinical development of oral SU006668 in humans.

PMID- 16406577
TI  - A simple and extremely sensitive system for detecting estrogenic activity using
      transgenic Arabidopsis thaliana.
AB  - Numerous physiological processes are regulated by endocrine systems in animals.
      Endocrine-disrupting chemicals (EDCs) can affect physiological processes of
      organisms by binding to hormone receptors. Therefore, it is necessary to develop
      methods for detecting EDCs and removing them from the environment. We have
      developed a simple and low-cost reporter gene assay system for the comprehensive
      analysis of estrogenic activity using transgenic Arabidopsis thaliana. This
      transgenic plant constantly expresses two effector proteins: a chimeric estrogen
      receptor and a chimeric nuclear receptor coactivator. Estrogen-dependent
      interaction between the two effector proteins triggers transcriptional activation
      of reporter gene, beta-glucuronidase. We have demonstrated this transgenic
      plant's capability of detecting the existence of 17beta-estradiol at a
      concentration of 50 pM (13 pg/ml) in agar medium. This plant can also detect
      other estrogenic substances, such as diethylstilbestrol, p-n-nonylphenol,
      bisphenol A, and Genistein.

PMID- 16406578
TI  - Molecular biomarkers of oxidative stress in aquatic organisms in relation to
      toxic environmental pollutants.
AB  - The potential of oxygen free radicals and other reactive oxygen species (ROS) to
      damage tissues and cellular components, called oxidative stress, in biological
      systems has become a topic of significant interest for environmental toxicology
      studies. The balance between prooxidant endogenous and exogenous factors (i.e.,
      environmental pollutants) and antioxidant defenses (enzymatic and nonenzymatic)
      in biological systems can be used to assess toxic effects under stressful
      environmental conditions, especially oxidative damage induced by different
      classes of chemical pollutants. The role of these antioxidant systems and their
      sensitivity can be of great importance in environmental toxicology studies. In
      the past decade, numerous studies on the effects of oxidative stress caused by
      some environmental pollutants in terrestrial and aquatic species were published.
      Increased numbers of agricultural and industrial chemicals are entering the
      aquatic environment and being taken up into tissues of aquatic organisms.
      Transition metals, polycyclic aromatic hydrocarbons, organochlorine and
      organophosphate pesticides, polychlorinated biphenyls, dioxins, and other
      xenobiotics play important roles in the mechanistic aspects of oxidative damage.
      Such a diverse array of pollutants stimulate a variety of toxicity mechanisms,
      such as oxidative damage to membrane lipids, DNA, and proteins and changes to
      antioxidant enzymes. Although there are considerable gaps in our knowledge of
      cellular damage, response mechanisms, repair processes, and disease etiology in
      biological systems, free radical reactions and the production of toxic ROS are
      known to be responsible for a variety of oxidative damages leading to adverse
      health effects and diseases. In the past decade, mammalian species were used as
      models for the study of molecular biomarkers of oxidative stress caused by
      environmental pollutants to elucidate the mechanisms underlying cellular
      oxidative damage and to study the adverse effects of some environmental
      pollutants with oxidative potential in chronic exposure and/or sublethal
      concentrations. This review summarizes current knowledge and advances in the
      understanding of such oxidative processes in biological systems. This knowledge
      is extended to specific applications in aquatic organisms because of their
      sensitivity to oxidative pollutants, their filtration capacity, and their
      potential for environmental toxicology studies.

PMID- 16406579
TI  - Excretion of three heavy metals in the shed skin of exposed corn snakes (Elaphe
      guttata).
AB  - Three heavy metals of regional environmental concern-lead, cadmium, and mercury
      are frequently evaluated as part of wildlife bioaccumulation and health
      monitoring studies. Shed skins of snakes may represent a useful, nonlethal
      biomarker tissue for such determinations. In the present study, these three heavy
      metals were injected into thawed mice that were fed to corn snakes (Elaphe
      guttata) such that snakes received 2mg/kg of each metal/month. Shed skins were
      collected over a period of 34 weeks, and levels of the heavy metals were
      determined in skins by atomic absorption methods. Each heavy metal was readily
      detected in the shed skins, with mean levels as follows: lead 234 ppb, cadmium
      806 ppb, and mercury 403 ppb. Control snakes that were fed nonmetal-injected mice
      produced shed skins that contained mean levels of 6, 12, and 20 ppb lead,
      cadmium, and mercury, respectively. These detection levels corresponded closely
      to expected trace metal contents of mouse chow and tap water. These results
      demonstrate that dietary metal exposure can be readily detected in shed snake
      skins, including at trace levels of exposure that may be consistent with, or
      below, environmental exposures.

PMID- 16406580
TI  - A case study on algal response to raw and treated effluents from an aluminum
      plating plant and a pharmaceutical plant.
AB  - The algal growth responses to the effluents of an aluminum plating plant and to
      the wastewater from an analgesic/antiinflammatory-drug-producing pharmaceutical
      plant were investigated. Growth response of the marine alga Dunaliella
      tertiolecta was monitored by measuring the two response parameters optical
      density (OD(640)) and in vitro chlorophyll fluorescence for a period of 14 days.
      Generally, the two response measurements gave similar results for all effluents
      but the raw effluents of the aluminum plating plant due to the composition of the
      wastewater. All wastes affected algal growth either by inhibition only or by
      stimulation at low concentrations and inhibition at high concentrations. Since
      pollutant tolerance of algae biased toxicity test results, acclimation of algae
      to the raw effluent of the aluminum plating plant was examined. Although the
      water quality parameters of treated effluent of both plants were in the permitted
      range reported by the Turkish Water Pollution Control Act, they inhibited growth
      at higher concentrations, implying that the two treatment plants were
      inefficient. Therefore, the importance of toxicity tests in wastewater discharge
      regulations was emphasized.

PMID- 16406581
TI  - Phytotoxicity of lanthanum in rice in haplic acrisols and cambisols.
AB  - Growth and physiological responses of rice to lanthanum were studied to elucidate
      the function of lanthanum in plants and its critical concentration relative to
      environmental safety. Shoot La content increased with the increasing added La
      concentrations. When shoot La content exceeded a toxic value, plant growth and
      chlorophyll a/b decreased and peroxidase (POD) activity, cell membrane
      permeability, and content of proline in the leaf increased. Leaf chlorophyll a/b
      and POD activity might provide useful criteria for early diagnoses of
      phytotoxicity of soil contaminated by La. In the present study, the critical
      concentration of La for rice relative to environmental safety was suggested to be
      42.03 mg kg(-1) in red soil and 83.33 mg kg(-1) in paddy soil.

PMID- 16406582
TI  - Oxidative stress on domestic ducks (Shaoxing duck) chronically exposed in a
      Mercury-Selenium coexisting mining area in China.
AB  - The Wanshan mercury mine is the largest mercury deposit in Guizhou Province,
      China. Few attempts have been made to study the toxic effects of mercury on biota
      in this mining area. This study was the first to investigate the oxidative stress
      on domestic ducks (Shaoxing duck) chronically exposed to mercury in the Wanshan
      mining area. Chemical analyses revealed higher concentrations of both, mercury
      and selenium in samples from the Wanshan area. Total mercury and selenium
      concentrations in duck tissues varied from 0.073 to 4.465 mg/kg and from 1.073 to
      6.35 mg/kg, respectively. Analysis of covariance revealed that there were
      significant effects of zone on accumulation of mercury and selenium in all duck
      tissues (P<0.01). Moreover, analysis of covariance indicated that mercury content
      significantly affected the accumulation of selenium in duck muscle, brain, and
      liver (P<0.01). Mercury and selenium were also highly correlated in Wanshan duck
      liver, muscle, brain, and lung. The statistical analysis suggested that selenium
      might be an interactive factor in mercury toxicity. As for the biochemical
      analyses, it was observed that selenium-dependent glutathione peroxidase and
      superoxide dismutase activities and glutathione (GSH) content were significantly
      increased in the livers and brains of Wanshan ducks (P<0.01, 0.05). However, no
      significant changes were observed in malondialdehyde content (P>0.05). Although
      the results indicated that adaptive responses of the redox-defense system are
      associated with the increased enzyme activities and GSH content, the most likely
      explanation is that selenium plays a critical role. Therefore, the effects of the
      interaction environmentally occurring selenium and mercury on public health in
      the Wanshan area should be examined in further studies.

PMID- 16406583
TI  - Effects of the benzoxazoid DIMBOA, selected degradation products, and structure
      related pesticides on soil organisms.
AB  - Both lethal and sublethal effects of the benzoxazoid 2,4-dihydroxy-7-methoxy-(2H)
      1,4-benzoxazin-3(4H)-one (DIMBOA), the degradation products 6-methoxy
      benzoxazolin-2(3H)-one (MBOA), 2-amino-7-methoxy-(3H)-phenoxazin-3-one (AMPO),
      and 2-acetylamino-7-methoxy-3(H)-phenoxazin-3-one (AAMPO) and the structure
      related compounds 2-methoxy-N-(2-oxo-1,3-oxazolidin-3yl)acet-2'=6'-xylidide
      (oxadixyl), and O,O-diethyl S-[6-chloro-2-oxobenzoxazolin-3
      yl)methyl]phosphorodithioate (phosalone) on the collembola Folsomia candida and
      on the carabid beetle Poecilus cupreus (except phosalone) were determined.
      Validated laboratory standard methods including reference and control treatments
      were applied in compliance with prescribed validity criteria. A risk assessment
      according to the EPPO risk assessment scheme for plant protection products (2003)
      was carried out. DIMBOA, MBOA, AMPO, AAMPO, and oxadixyl were classified as low
      risk compounds for both test organisms. The reference compounds methyl-m-hydroxy
      carbanilate-methyl-carbanilate (phenmedipham) and O,O-dimethyl S-[2-(methylamino)
      2-oxoethyl]phosphoro-dithioate (dimethoate) were of low and medium risk
      respectively, to F. candida, but final assessment of the risk to P. cupreus
      requires further testing. Phosalone was of high risk to F. candida. The results
      obtained suggest that neither DIMBOA nor the tested degradation products pose a
      risk to either nontarget soil organism in the field.

PMID- 16406584
TI  - An approach to feeding high-percentage fish diets to mice for human and wildlife
      toxicology studies.
AB  - Experimental feeding of sport fish to rodents has been an important tool for the
      study of biological effects induced by a contaminated fish diet. Most rodent
      feeding studies have used low-to-moderate levels of tissue from large fish
      species incorporated into diets fed to rats and have given little consideration
      to issues of diet palatability or nutrition. There are currently no rodent diet
      models suitable for assessing the risk to human populations of diets very high in
      daily fish content or to wildlife species consuming high percentages of whole,
      small-bodied fish. In this study, we describe an approach to feeding mice high
      percentages (up to 50%) of homogenized, whole fish using Atlantic herring (Clupea
      harengus) as a test species. We created a novel gel diet medium for mice that
      contains a variety of nutritional supplements and is flexible in terms of the
      fish percentage that can be incorporated. In choice trials, mice preferred 30 and
      35% fish gels to their regular commercial dry chow, indicating that the gel diet
      medium was palatable. In a longer feeding trial, mice ate 35% fish gel for 12
      days and 50% fish gel for 12 days (total of 24 consecutive days) and did not
      differ in body mass compared to age- and sex-matched controls. We conclude that
      our fish-based gel diet is suitable for rodent feeding trials in toxicology
      studies that examine dose responses to fish consumption and risk in human and
      wildlife populations among which daily fish intake is very high. Our general
      approach may also be applicable for feeding mice materials other than fish.

PMID- 16406585
TI  - Vermiconversion of wastewater sludge from textile mill mixed with anaerobically
      digested biogas plant slurry employing Eisenia foetida.
AB  - Vermicomposting is commonly used for the management of organic wastes. We have
      investigated the potential of an epigeic earthworm, Eisenia foetida, to transform
      solid textile mill sludge (STMS) spiked with anaerobically digested biogas plant
      slurry (BPS) into vermicompost to evaluate the feasibility of vermicomposting in
      industries for waste management. The growth and reproduction of E. foetida was
      monitored in a range of different feed mixtures for 15 weeks in laboratory under
      controlled experimental conditions. E. foetida did not survive in fresh STMS. But
      worms grew and reproduced in STMS spiked with BPS feed mixtures. A greater
      percentage of STMS in feed mixture affected biomass gain and cocoon production by
      earthworms. The maximum growth was recorded in 100% BPS. The net weight gain by
      E. foetida in 100% BPS was two-four-fold higher than STMS-containing feed
      mixtures. After 15 weeks, maximum cocoons (78) were counted in 100% BPS and
      minimum (26) in 60% BPS+40% STMS feed. Vermicomposting resulted in pH shift
      toward acidic, significant reduction in C:N ratio, and increase in nitrogen,
      phosphorus, and potassium contents. Microbial activity measured as dehydrogenase
      activity increased with time up to day 75 but decreased on day 90, indicating the
      exhaustion of feed and decrease in microbial activity. These experiments
      demonstrate that vermicomposting can be an alternate technology for the recycling
      and environmentally safe disposal/management of textile mill sludge using an
      epigeic earthworm, E. foetida, if mixed with anaerobically digested BPS in
      appropriate ratios.

PMID- 16406586
TI  - Acute toxic tests of rainwater samples using Daphnia magna.
AB  - Rainwater samples were collected at Isogo Ward of Yokohama City, Japan, from 23
      June to 31 July 2003. The toxic potency of pollutants present in 13 rainwater
      samples was tested using Daphnia magna. Most test animals died within 48 h in
      five test solutions that were prepared from rainwater samples. On the other hand,
      when nonpolar compounds such as pesticides were removed from rainwater samples
      before the toxic tests, mortalities in all test solutions were less than 10%.
      Eight kinds of pesticides were detected in rainwater samples. The highest
      concentration was of dichlorvos, at 0.74 microg/L. Results indicated that
      insecticides in rainwater sometimes lethally affected D. magna and that toxic
      potency of insecticides that are present in rainwater constitutes an important
      problem for environmental protection.

PMID- 16406587
TI  - Toxicity and gross pathology of ivermectin bath treatment in sea bream Sparus
      aurata, L.
AB  - The isopod parasite Ceratothoa oestroides becomes hard to eradicate in intensive
      fish rearing systems and in addition to causing weight loss in adult fish it
      causes mortalities in larval and juveniles stages of sea bass and sea bream.
      Faced with the fast emergence of this infection in Adriatic finfish facilities,
      an effective compound had to be tested for bath treatment. Ivermectin was chosen
      for this purpose on the basis of extensive practice in northern European
      countries which used ivermectin administered in food with good results in
      treatment of Lepeophtheirus sp. and Caligus sp. infections. For determination of
      toxicity of ivermectin, a short-term toxicity bioassay on 40-day-old sea bream,
      Sparus aurata, L., was conducted, following FAO and UNEP procedures for
      methodology in aquatic toxicity trials. Median survival time, slope functions,
      and 95% confidence limits for ivermectin showed moderate toxicity in sea bream,
      with first 100% mortalities during 96h at the concentration of 1.8 mg/L.

PMID- 16406588
TI  - Assessment of the effects of imidacloprid on the behavior of two earthworm
      species (Aporrectodea nocturna and Allolobophora icterica) using 2D terraria.
AB  - Earthworms are "ecosystem engineers" and changes in their main activities
      (creation of burrows and burial of organic matter) due to pollutants can have
      important effects on soil functions and indirectly on other components of the
      soil ecosystem. Using 2D terraria, we studied the behavior of two earthworm
      species (the endogeic Allolobophora icterica and the anecic Aporrectodea
      nocturna) exposed to sublethal concentrations (0.5 and 1 mg kg(-1) of dry soil)
      of imidacloprid, a widely used neonicotinoid insecticide. A second experiment was
      carried out to determine whether such imidacloprid concentrations were avoided by
      the two earthworm species we studied. In polluted soils, significant weight loss
      was observed in both species. No significant avoidance of imidacloprid was
      detected, whereas several modifications of the behavior were observed directly
      (burrowing dynamics, number of oscillations in the burrow system) or indirectly
      in the resulting burrow system architecture (area, topology, sinuosity maximal
      depth) according to the species and concentration tested. When exposed to
      imidacloprid (0.5 or 1 mg kg(-1)), A. icterica almost stopped burrowing after 24
      h, whereas A. nocturna burrowed continuously but with a significantly lower rate
      compared to the control. Moreover, in both species, the burrow systems were
      always shallower when worms were exposed to imidacloprid. Since this last
      endpoint is easy to measure and is linked to water transfer in soils, it could be
      used in ecotoxicological studies provided it could be validated for a wide range
      of pollutants and concentrations.

PMID- 16406589
TI  - Effects of five rice herbicides on the growth of two threatened aquatic ferns.
AB  - The effects of five rice herbicides bensulfuron methyl, mefenacet, quinoclamine,
      simetryn, and thiobencarb on the growth of two threatened aquatic ferns Azolla
      japonica and Salvinia natans were tested using 12-day exposure experiments at 0.1
      100 nM which are expected to be present in drainages and rivers in Japan. As a
      reference species, Lenma minor was also used to examine the toxicity of
      bensulfuron methyl. Bensulfuron methyl had the most pronounced effect on the
      relative growth rate (RGR) of A. japonica, S. natans, and L. minor with an EC50
      of 5.0, 0.54, and 10 nM, respectively. The other herbicides reduced the RGR of
      the aquatic ferns only at the highest concentration (100 nM) or not at all. S.
      natans showed the highest susceptibility to bensulfuron methyl among the three
      species, and the EC50 for this species was comparable to or below the maximum
      concentration (0.49-5.6 nM) that had been previously detected in 7 of 11 rivers
      in Japan. These results suggest that bensulfuron methyl runoff in drainages and
      rivers in Japan is expected to have adverse effects on the growth of threatened
      aquatic ferns in some cases, and that no or small effects occur for the other
      four herbicides tested.

PMID- 16406590
TI  - Use of two biomarkers (CYP450 and acetylcholinesterase) in zebra mussel for the
      biomonitoring of Lake Maggiore (northern Italy).
AB  - The use of zebra mussel Dreissena polymorpha as a bioaccumulator for lipophilic
      compounds is nowadays standardized, but its employment in early warning systems
      by the biomarker approach is much less frequent. One of the main problems with
      the biomarker approach is due to natural variation of abiotic factors such as
      temperature that influence the activity of several enzymes. In this study, we
      investigated the influence of this environmental parameter on the activities of
      two different biomarkers: acetylcholinesterase (AChE) (inhibited by
      organophosphorus compounds) and CYP450 (inversely influenced by planar compounds
      and heavy metals). We used these two biomarkers to evaluate the environmental
      pollution of Lake Maggiore (northern Italy). Results showed a strong AChE
      inhibition in mussel specimens collected in some sampling sites of the lake,
      indicating heavy pollution by neurotoxic compounds. We also found a twofold
      effect on CYP450 activity, probably due to the activating effect of planar
      compounds and the inhibiting effect of trace metals.

PMID- 16406591
TI  - Depuration of microcystins in tilapia fish exposed to natural populations of
      toxic cyanobacteria: a laboratory study.
AB  - Previous studies demonstrated that microcystins (MCYSTs) can be accumulated in
      different organs, particularly the liver, of tilapia fish (Oreochromis niloticus)
      in an Egyptian fish farm containing toxic blooms of Microcystis aeruginosa. In
      the present study, a microcosm experiment was conducted to examine the depuration
      of MCYSTs in tilapia fish from this fish farm. Fish were grown in a 100-L aerated
      recirculation tank containing dechlorinated water at room temperature (25+/-2
      degrees C) for 96 h. MCYST concentrations in livers, intestines, and gallbladders
      of each daily sacrificed fish were determined by both enzyme-linked immunosorbent
      assay (ELISA) and protein phosphatase inhibition assay (PPIA). MCYST
      concentrations in the surrounding water were also determined by the same methods.
      The results showed that MCYST concentrations in the liver and intestine decreased
      gradually throughout the experimental period. This decrease was accompanied by an
      increase in MCYST concentrations in the gallbladder and surrounding water. The
      maximum value of MCYST in the surrounding water was obtained after 96 h at a
      level of 1.2 microg/L by ELISA, while it was obtained after 24 h at a level of
      0.5 microg/L by PPIA and remained stable until the end of the experiment. The
      present study revealed that tilapia fish can depurate and excrete MCYSTs into the
      bile and surrounding water as a way to avoid toxicity from such a potent
      hepatotoxin.

PMID- 16406592
TI  - Crystalline style and tissue redistribution in Perna viridis as indicators of Cu
      and Pb bioavailabilities and contamination in coastal waters.
AB  - The concentrations of Cu, Pb, and Zn in the crystalline style (CS) and in the
      remaining soft tissues (ST) of the green-lipped mussel Perna viridis from 10
      geographical sites along the coastal waters off peninsular Malaysia were
      determined. The CS, compared with the remaining ST, accumulated higher levels of
      Cu in both contaminated and uncontaminated samples, indicating that the style has
      a higher affinity for the essential Cu to bind with metallothioneins. The similar
      pattern of Cu accumulation in the different ST of mussels collected from clean
      and Cu-contaminated sites indicated that the detoxification capacity of the
      metallothioneins had not been overloaded. For Pb, higher levels of the metal in
      the CS than in the remaining ST were found only in mussels collected from a
      contaminated site at Kg. Pasir Puteh. This indicated a tissue redistribution of
      Pb due to its binding to metallothioneins for Pb detoxification and the potential
      of the CS as an indicator organ of Pb bioavailability and contamination. For Zn,
      the above two phenomena were not found since no obvious patterns were observed
      (lower levels of Zn in the CS than in the remaining ST) in contaminated and
      uncontaminated samples due to the mechanism of partial regulation. Generally, all
      the different STs studied (foot, mantle, gonad, CS, gill, muscle, and byssus) are
      good biomonitoring tissues for Cu and Pb bioavailabilities and contamination.
      Among these organs, the CS was found to be the best organ for biomonitoring Cu.
      The present data also suggest the use of the tissue redistribution of Pb in P.
      viridis as an indicator of Pb bioavailability and contamination in coastal
      waters.

PMID- 16406593
TI  - Triphenyltin and tributyltin, single and in combination, promote imposex in the
      gastropod Bolinus brandaris.
AB  - Specimens of Bolinus brandaris (neogastropod) were injected with a single dose of
      500 ng/g body weight (b.w.) of tributyltin chloride (TBTCl) or triphenyltin
      chloride (TPTCl), or a mixture of both compounds (250 ng TBT/g b.w.+250 ng TPT/g
      b.w.), for a period of up to 31 days. At the end of 4 weeks, significant
      increases in the female penis size of those gastropods injected with TBT
      (P<0.05), TPT (P<0.05), or the mixture TBT+TPT (P<0.01) were recorded. In
      parallel, a group of animals was injected with the neuropeptide APGWamide but
      this compound failed to promote imposex, suggesting that APGWamide is not
      involved in imposex promotion in B. brandaris. Acetylcholinesterase activity, a
      biomarker of neurotoxicity, was determined in the neuroganglia at the end of the
      experiment, but no significant differences among treatments were found. Overall,
      these results support the hypothesis that TPT also acts as an endocrine disrupter
      in this neogastropod species. Our observations also highlight, for the first
      time, synergistic effects of organotin mixtures having imposex promotion as an
      endpoint.

PMID- 16406594
TI  - A comparative study of rac- and S-metolachlor toxicity to Daphnia magna.
AB  - Racemic product of metolachlor contains two R enantiomers and two S enantiomers.
      S-metolachlor is now widely used instead of rac-metolachlor because the former is
      more effective in herbicidal activity than the latter. The acute and chronic
      toxicities of rac- and S-metolachlor to Daphnia magna were determined and
      compared in this study. The acute 24-h LC50s for rac- and S-metolachlor to D.
      magna were 69.4 and 51.2 mgL(-1), respectively, indicating that the acute
      toxicity of S-metolachlor is slightly higher than that of rac-metolachlor. In
      chronic test, lowest-observed-effect concentration (LOEC), no-observed-effect
      concentration (NOEC), days to first brood, length, longevity, number of broods
      per female, number of young per female, and the intrinsic rate of natural
      increase (r) were determined. The results showed that the LOEC and NOEC of rac
      metolachlor were 0.01 and 0.001 mgL(-1), while those of S-metolachlor were 0.5
      and 0.1 mgL(-1), respectively. The first brood day of D. magna was not affected
      by rac- or S-metolachlor. Longevity and the number of broods per female were
      significantly (P<0.05) affected when rac-metolachlor concentration was higher
      than 1.0 mgL(-1) but were not significantly affected until S-metolachlor
      concentration was higher than 10 mgL(-1). The length was affected at the same
      concentration of rac- and S-metolachlor. Number of brood per female was
      significantly reduced when rac-metolachlor concentration was higher than 0.01
      mgL(-1) but not significantly reduced until S-metolachlor concentration was
      higher than 0.5 mgL(-1). The r values were significantly reduced when the rac
      metolachlor concentrations were above 0.01 mgL(-1) but not reduced only when S
      metolachlor concentration was higher than 0.5 mgL(-1). The results of chronic
      toxicity indicated that rac-metolachlor was significantly (P<0.05) more toxic
      than S-metolachlor to D. magna.

PMID- 16406595
TI  - Municipal landfill leachate induces cytogenetic damage in root tips of Hordeum
      vulgare.
AB  - With increasing use of municipal solid waste landfills for solid waste disposal,
      municipal landfill leachate has become a serious concern for aquatic
      environments. Therefore, it is important to study its toxic effects on plants,
      animals, and humans. In the present study, the genotoxicity of leachate was
      investigated with the Hordeum vulgare root-tip cytogenetic bioassay, using
      Chemical oxygen demand (COD(Cr)) as a measure of leachate concentration. Leachate
      decreased the mitotic index (MI) in a concentration-dependent and a time
      dependent manner. Compared with the negative control, reductions of MI of 37%,
      56%, and 70% were detected for the highest leachate concentration (COD(Cr) 800
      mg/L) in root tips treated for 24, 48, and 72 h, respectively. Leachate caused
      significant increases of micronucleus (MCN) frequencies in a concentration
      dependent and a time-dependent manner. Among the exposure groups, COD(Cr) 40 mg/L
      leachate induced MCN formation after 24, 48, and 72 h of exposure, and the
      frequencies of MCN significantly increased with increasing concentrations of
      leachate from COD(Cr) 40 to 640 mg/L. In addition, pycnotic cells (PNC) occurred
      in root tips at all leachate concentrations tested after 24, 48, and 72 h of
      exposure, and PNC frequencies had a positive relation with the treatment
      concentration and the exposure time. The results also indicate that the
      concentration required to produce cytogenetic damage was lower in cells that had
      a longer exposure time. The results confirm that components of leachate may be
      genotoxic in plant cells and imply that long exposure to leachate at low
      concentrations in the aquatic environment may pose a potential genotoxic risk to
      organisms. The results suggest that the H. vulgare cytogenetic bioassay is
      efficient, simple, and reproducible in genotoxicity studies of leachate, and that
      there appears to be a correlation between the genotoxicity in a plant system and
      the COD(Cr) of leachate.

PMID- 16406596
TI  - Bioaccumulation and antioxidant responses in goldfish Carassius auratus under HC
      Orange No. 1 exposure.
AB  - HC Orange No. 1 is used as a color additive in hair dyes and colors. In this
      study, laboratory experiments were carried out to determine the accumulation of
      HC Orange No. 1 in goldfish and the biochemical responses in liver of freshwater
      goldfish Carassius auratus. Goldfish were exposed to 1.0 mg/L HC Orange No. 1 for
      6, 12, 24, 36, 48, 60, 72, and 96 h. Results showed that the concentrations of HC
      Orange No. 1 in water decreased rapidly in the first 24h, and then maintained
      equilibrium, while the concentrations of HC Orange No. 1 in goldfish reached a
      maximum level at 24 h, and then descended appreciably. For the total loss of HC
      Orange No. 1 in water 16.4% was due to the accumulation by goldfish, and
      approximately 57.6% resulted from metabolism by goldfish. After calculation,
      lgBCF is equal to 2.11. Hence, HC Orange bioaccumulation is significantly
      affected by a fast metabolic clearance in goldfish. Next, we investigated the
      biochemical responses in liver of freshwater goldfish C. auratus. It was shown
      that the hepatic antioxidant defense parameters of goldfish, including the
      contents of reduced glutathione (GSH) and activities of superoxide dismutase
      (SOD), catalase (CAT), glutathione S-transferase (GST), were highly sensitive to
      HC Orange No. 1 exposure, accompanied by changes of HC Orange No. 1 accumulation
      in liver tissue. Changes of these parameters indicated that there was an increase
      in the production of oxyradicals by goldfish and the presence of oxidative
      stress. These findings also implied that glutathione as well as other antioxidant
      enzymes function in the protection against HC Orange No. 1 toxicity and that
      these antioxidants provide a first line of defense against HC Orange No. 1,
      before the induction of any other detoxification mechanism.

PMID- 16406597
TI  - Response of meiofauna and nematode communities to increased levels of
      contaminants in a laboratory microcosm experiment.
AB  - This study was undertaken to assess the response of meiofauna and nematode
      (multispecies) associations in terms of density, diversity, and composition to
      different environmental contaminants and also to evaluate the use of meiofauna
      and nematodes as indicators in pollution monitoring. Sediment was collected from
      the mouth of the Swartkops River estuary and defaunated by successive freezing
      and thwarting. The sediment was then subdivided into flasks and treated with
      different contaminants (organic carbon, Zn, Cu, Pb, Fe) at different
      concentrations, before meiofauna-rich sediment was added to each of them. The
      setup was allowed to mature for 32 days. Various biological indices were used to
      assess the biological status of the nematode communities in the laboratory
      experiment. Nematode identification was done to the genus level. The results
      indicate that higher concentrations of heavy metals and organic carbon had an
      impact on the nematode density, diversity, and community structure. Nematode
      genera such as Axonolaimus, Theristus, and Paramonohystera were found to be
      tolerant to metal pollution. This study also observed that nematode communities
      react differently to metal and organic pollution.

PMID- 16406598
TI  - Combined effect of heavy metals and polycyclic aromatic hydrocarbons on urease
      activity in soil.
AB  - Actions and interactions between heavy metals (HM)-cadmium, zinc, lead, and
      polycyclic aromatic hydrocarbons (PAHs)-phenanthrene, fluoranthene,
      benzo(a)pyrene toward soil urease activity were studied after 7, 14, 21, and 28
      days of exposure under controlled conditions. The experimental approach was based
      on the uniform design. Ten different contamination conditions were studied
      simultaneously, with 10 concentration levels for each pollutant. Data treatment
      was essentially based on the multiple regression technique. The results showed
      that Zn interacted more easily with PAHs than Pb or Cd. On the first 7 days of
      incubation, zinc alone reduced the urease activity more significantly than any
      other pollutants and no significant interactions between PAH and HM were
      observed. From 14 to 21 days of incubation, the interaction between Zn and
      benzo(a)pyrene decreased the soil urease activity. At 14 days, the interaction
      between Zn and phenanthrene was antagonistic (less than additive), while at 21
      days it was synergistic (more than additive). At 28 days, the interaction between
      phenanthrene and fluoranthene was synergistic. This study indicated that the
      combined effect of PAH and HM on soil urease activity depends largely on the
      incubation time. Uniform design appears to be a good method for investigating the
      combined effect of PAH and HM.

PMID- 16406599
TI  - Pectinase production by solid fermentation from Aspergillus niger by a new
      prescription experiment.
AB  - The Ordos Plateau in China is covered with up to 300,000 ha of peashrub
      (Caragana) which is the dominant natural vegetation and ideal for fodder
      production. To exploit peashrub fodder, it is crucially important to optimize the
      culture conditions, especially culture substrate to produce pectinase complex. In
      this study, a new prescription process was developed. The process, based on a
      uniform experimental design, first optimizes the solid substrate and second,
      after incubation, applies two different temperature treatments (30 degrees C for
      the first 30 h and 23 degrees C for the second 42 h) in the fermentation process.
      A multivariate regression analysis is applied to a number of independent
      variables (water, wheat bran, rice dextrose, ammonium sulfate, and Tween 80) to
      develop a predictive model of pectinase activity. A second-degree polynomial
      model is developed which accounts for an excellent proportion of the explained
      variation (R(2)=97.7%). Using unconstrained mathematical programming, an
      optimized substrate prescription for pectinase production is subsequently
      developed. The mathematical analysis revealed that the optimal formula for
      pectinase production from Aspergillus niger by solid fermentation under the
      conditions of natural aeration, natural substrate pH (about 6.5), and
      environmental humidity of 60% is rice dextrose 8%, wheat bran 24%, ammonium
      sulfate ((NH(4))(2)SO(4)) 6%, and water 61%. Tween 80 was found to have a
      negative effect on the production of pectinase in solid substrate. With this
      substrate prescription, pectinase produced by solid fermentation of A. niger
      reached 36.3 IU/(gDM). Goats fed on the pectinase complex obtain an incremental
      increase of 0.47 kg day(-1) during the initial 25 days of feeding, which is a
      very promising new feeding prospect for the local peashrub. It is concluded that
      the new formula may be very useful for the sustainable development of arid and
      semiarid pastures such as those of the Ordos Plateau.

PMID- 16406600
TI  - Estradiol reduces cumulative mercury and associated disturbances in the
      hypothalamus-pituitary axis of ovariectomized rats.
AB  - The aim of this research was to verify the incidence of endocrine dysfunction
      associated with mercury intoxication in the hypothalamus-pituitary reproductive
      system of normally cycling or castrated female rats and the possible protective
      action of estrogen replacement therapy. We found no differences in the frequency
      of estrus cycle stages (diestrus I, diestrus II, proestrus, and estrus) in
      normally cycling female rats during 54 days of daily oral administration of
      0.004, 0.02, and 1 mg/kg MeHgCl. Conversely, the higher dose (1 mg/kg) induced a
      significant decrease in content of luteinizing hormone releasing hormone (LHRH)
      into the medial hypothalamus when administered daily during 3 days in
      ovariectomized rats. This effect was associated with increased levels of mercury
      found in the anterior pituitary gland and medial hypothalamus, rather than the
      anterior and posterior hypothalamus, striatum or cerebellum. A decrease in plasma
      levels of luteinizing hormone (LH) was also detected after administration of 7.5
      mg/kg MeHgCl. These disturbances in LHRH and LH secretion induced by mercury were
      abolished or superimposed (respectively) by estrogenic replacement therapy (0.025
      mg/kg 17beta estradiol cypionate, intramuscular). These effects were associated
      with a significant reduction in mercury content of the anterior pituitary gland
      and medial hypothalamus, suggesting a protective estrogenic effect.

PMID- 16406601
TI  - Toxicity assessment of 40 herbicides to the green alga Raphidocelis subcapitata.
AB  - The effects of 40 herbicides with nine modes of action on the green alga
      Raphidocelis subcapitata were studied by 96-h acute toxicity tests. Results
      showed that the EC50 of the herbicides with respect to the photosynthetic
      processes of R. subcapitata ranged from 0.0007 to 4.2286 mgL(-1). Photosynthesis
      was the process of the green alga most sensitive to the tested herbicides. The
      most toxic herbicides were atrazine, ametryme, simazine, prometryne, cyanazine,
      isoproturon, chlorotoluron, diuron, methabenzthiazuron, and paraquat. The EC50 of
      the protoporphyrinogen oxidase inhibitor oxadiargyl, which was the parameter
      least sensitive to the herbicides tested in this study, was 42.5 mgL(-1). The
      descending order of the average acute toxicity to R. subcapitata of herbicides
      with regard to the nine modes of action was as follows: photosynthetic
      process>cell division>lipid synthesis, acetyl-coenzyme A carboxylase>acetolactate
      synthase> 5-enolpyruvyl-shikimate-3-phosphate synthase, glutamine synthase,
      hormone synthesis>protoporphyrinogen oxidase.

PMID- 16406602
TI  - A phase II study of carboplatin and paclitaxel as first line chemotherapy in
      elderly patients with advanced non-small cell lung cancer (NSCLC).
AB  - INTRODUCTION: Lung cancer is the leading cause of tumour-related deaths in the
      elderly population but the optimal management of advanced NSCLC in older patients
      has not been defined to date. The present phase II study was planned to evaluate
      the efficacy and toxicity of the combination of carboplatin and paclitaxel in
      elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients (>70 years
      old) who had pathologically been proven to have a NSCLC and measurable lesions
      were treated with paclitaxel (175 mg/m2 for 3h) and carboplatin [area under the
      concentration-time curve (AUC=5)] on day 1 every 3 weeks. RESULTS: Forty patients
      were enrolled into the study. The median age was 74 years (range, 70-78 years).
      Approximately 85% of the patients had stage IV and 80% had a performance status
      (PS) of 0-1. Nine of the 40 (22.5%; 90% CI 17.6-28.1) included patients had a
      partial response; one patient (2.5%; 90% CI 1.7-3.2) achieved a complete
      response. The overall response rate was 25% (90% CI 15.3-38.6). In addition
      stable disease was observed in 13 patients (32.5%; 90% CI 24.3-40.7). The median
      survival was 7.8 months (95% confidence interval, 5.1-11.8 months). The actual 1
      year survival was 18% (95% confidence interval, 12-29%). The median time to
      disease progression was 4.1 months (95% CI 2.8-8.5). Overall, 37.5% of patients
      experienced grade 3-4 neutropenia of any duration with only two patients (5%)
      developing neutropenic fever. Grade 3 or 4 non-haematological toxicity was
      uncommon apart alopecia. CONCLUSIONS: In the present phase II study the
      combination of paclitaxel and carboplatin has demonstrated to be active and safe
      in an age-selected population.

PMID- 16406603
TI  - Active leg stiffness and energy stored in the muscles during maximal counter
      movement jump in the aged.
AB  - The purpose of this study was to examine the effects of age on active leg
      stiffness adjustment, electromyogram (EMG) activities and energy stored during
      eccentric and concentric phases in performing a maximal functional task involving
      stretch-shorten cycle. Ten young (24.3+/-2 years) and 10 old (68.6+/-5 years)
      healthy male subjects were filmed during maximal performance of counter movement
      jump (CMJ) and squat jump (SJ) on force plate. Integrated EMG (IEMG), ground
      reaction force (GRF), active leg stiffness, energy stored/returned and active
      work done by the muscles were compared between two groups on eccentric (ECC) and
      concentric (CON) phases of CMJ. The GRF, leg stiffness and energy stored in ECC
      and GRF, IEMG, energy returned and active work in CON were less in the elderly
      (p<0.05). These results demonstrate that the neuromuscular function of adjusting
      active stiffness, storing elastic energy and optimizing the performance may
      decrease with age during CMJ.

PMID- 16406605
TI  - Evaluation of long-term sulfide oxidation processes within pyrrhotite-rich
      tailings, Lynn Lake, Manitoba.
AB  - Oxidation reactions have depleted sulfide minerals in the shallow tailings and
      have generated sulfate- and metal-rich pore water throughout the East Tailings
      Management Area (ETMA) at Lynn Lake, Manitoba, Canada. Information concerning the
      tailings geochemistry and mineralogy suggest the sulfide oxidation processes have
      reached an advanced stage in the area proximal to the point of tailings
      discharge. In contrast, the distal tailings, or slimes area, have a higher
      moisture content close to the impoundment surface, thereby impeding the ingress
      of oxygen and limiting sulfide oxidation. Numerical modelling of sulfide
      oxidation indicates the maximum rate of release for sulfate, Fe, and Ni occurred
      shortly after tailings deposition ceased. Although the sulfide minerals have been
      depleted in the very shallow tailings, the modelling suggests that sulfide
      oxidation will continue for hundreds and possibly thousands of years. The
      combination of sulfide minerals, principally pyrrhotite, that is susceptible to
      weathering processes and the relatively dry, coarse-grained nature of the
      tailings have resulted in the formation of a massive-hardpan layer in the
      proximal area of the ETMA. Because extensive accumulations of secondary
      oxyhydroxides of ferric iron are already present, remediation strategies for the
      ETMA should focus on mitigating the release of sulfide oxidation products rather
      than on preventing further oxidation.

PMID- 16406604
TI  - Dexamethasone induces rapid tyrosine-phosphorylation of ZAP-70 in Jurkat cells.
AB  - Steroid hormones are known to mediate rapid non-genomic effects occurring within
      minutes, besides the classical genomic actions mediated by the nuclear
      translocation of the cytoplasmic glucocorticoid receptor (GR). The glucocorticoid
      hormone (GC) has significant role in the regulation of T-cell activation;
      however, the cross-talk between the GC and T-cell receptor (TcR) signal
      transducing pathways are still to be elucidated. We examined the rapid effects of
      GC exposure on in vitro cultured human T-cells. Our results showed that
      Dexamethasone (DX), a GC analogue, when applied at high dose (10 microM), induced
      rapid (within 5 min) tyrosine-phosphorylation events in Jurkat cells. Short DX
      pre-treatment strongly inhibited the tyrosine-phosphorylation stimulated by CD3
      cross-linking. Furthermore, we also investigated the phosphorylation status of
      ZAP-70, an important member of tyrosine kinase mediated signalling pathway of TcR
      elicited T-cell activation. Here, we demonstrate that high dose DX induced a
      rapid ZAP-70 tyrosine-phosphorylation in Jurkat T-cells. DX-induced ZAP-70
      phosphorylation could be inhibited by RU486 (GR antagonist), suggesting that this
      process was GR mediated. DX-induced ZAP-70 phosphorylation did not occur in the
      absence of active p56-lck as examined in the p56-lck kinase-deficient Jurkat cell
      line JCaM1.6. Our results show that DX, at a high dose, can rapidly influence the
      initial tyrosine-phosphorylation events of the CD3 signalling pathway in Jurkat
      cells, thereby modifying TcR-derived signals. Lck and ZAP-70 represent an
      important molecular link between the TcR and GC signalling pathways.

PMID- 16406606
TI  - Similar brain networks for detecting visuo-motor and visuo-proprioceptive
      synchrony.
AB  - The ability to recognize feedback from own movement as opposed to the movement of
      someone else is important for motor control and social interaction. The neural
      processes involved in feedback recognition are incompletely understood. Two
      competing hypotheses have been proposed: the stimulus is compared with either (a)
      the proprioceptive feedback or with (b) the motor command and if they match, then
      the external stimulus is identified as feedback. Hypothesis (a) predicts that the
      neural mechanisms or brain areas involved in distinguishing self from other
      during passive and active movement are similar, whereas hypothesis (b) predicts
      that they are different. In this fMRI study, healthy subjects saw visual cursor
      movement that was either synchronous or asynchronous with their active or passive
      finger movements. The aim was to identify the brain areas where the neural
      activity depended on whether the visual stimulus was feedback from own movement
      and to contrast the functional activation maps for active and passive movement.
      We found activity increases in the right temporoparietal cortex in the condition
      with asynchronous relative to synchronous visual feedback from both active and
      passive movements. However, no statistically significant difference was found
      between these sets of activated areas when the active and passive movement
      conditions were compared. With a posterior probability of 0.95, no brain voxel
      had a contrast effect above 0.11% of the whole-brain mean signal. These results
      do not support the hypothesis that recognition of visual feedback during active
      and passive movement relies on different brain areas.

PMID- 16406607
TI  - Anti-fungal activity of crude extracts and essential oil of Moringa oleifera Lam.
AB  - Investigations were carried out to evaluate the therapeutic properties of the
      seeds and leaves of Moringa oleifera Lam as herbal medicines. Ethanol extracts
      showed anti-fungal activities in vitro against dermatophytes such as Trichophyton
      rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum
      canis. GC-MS analysis of the chemical composition of the essential oil from
      leaves showed a total of 44 compounds. Isolated extracts could be of use for the
      future development of anti-skin disease agents.

PMID- 16406608
TI  - Removal of chlorophenols in sequential anaerobic-aerobic reactors.
AB  - Combination of upflow anaerobic sludge blanket (UASB) and aerobic rotating
      biological contactor (RBC) reactors having higher biomass concentration and
      higher sludge retention time (SRT) was applied for the sequential treatment of
      priority pollutant chlorophenol containing wastewater. Target compounds 2
      chlorophenol (2-CP) and 2,4-dichlorophenol (2,4-DCP) present in two simulated
      wastewaters at a concentration of 30 mg/l each individually were sequentially
      treated in continuous mode by combined UASB-I, RBC-I and combined UASB-II, RBC-II
      reactors, respectively after the acclimation of their biomass with the
      corresponding chlorophenol. Reactor combinations took 190 and 215 days for
      acclimation with 30 mg/l of 2-CP and 2,4-DCP respectively. Hydraulic retention
      time (HRT) studies showed that 12h HRT of UASB-I and 23 h HRT of RBC-I as well as
      12h HRT of UASB-II and 28.8h HRT of RBC-II were the optimum combinations for the
      treatment of simulated wastewater containing 2-CP and 2,4-DCP respectively.
      Optimum HRT combinations produced 2-CP and 2,4-DCP effluent having corresponding
      chlorophenol concentration of below detectable limit (BDL) and 0.1 mg/l
      respectively. Half velocity coefficients (Ks) for 2-CP and 2,4-DCP biodegradation
      in UASB reactors were determined to be 5.07 mg 2-CP/l and 6.49 mg 2,4-DCP/l.
      Optimum ratio of substrate (chlorophenol): co-substrate (sodium acetate) was
      1:100.

PMID- 16406609
TI  - PI3K is required for insulin-stimulated but not EGF-stimulated ERK1/2 activation.
AB  - The Ras/Raf/extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling
      pathway is known to cross-talk with other signaling pathways, including
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, the role of PI3K in
      ERK-1/2 activation induced by tyrosine kinase receptors was not fully understood.
      Here, we report that two structurally distinct PI3K inhibitors, wortmannin and
      LY294002, inhibited insulin-induced activation of ERK1/2 but had no effect on EGF
      induced activation of ERK1/2 in hepatocellular carcinoma BEL-7402 and SMMC-7721
      cells, breast cancer MCF-7 cells, and prostate cancer LNCaP cells. Although
      protein kinase C could act as a mediator between PI3K and ERK1/2, protein kinase
      C inhibitor chelerythrine chloride did not inhibit insulin-induced ERK1/2
      activation. Both insulin- and EGF-induced ERK1/2 activation are strictly
      dependent on Ras activation, however, wortmannin only inhibited insulin-induced,
      but not EGF-induced Ras activation. These results indicate that PI3K plays
      different roles in the activation of Ras/ERK1/2 signaling by insulin and EGF, and
      that insulin-stimulated, but not EGF-stimulated, ERK1/2 and Akt signalings
      diverge at PI3K.

PMID- 16406610
TI  - The area composita of adhering junctions connecting heart muscle cells of
      vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by
      immunoelectron microscopy of desmosomal proteins.
AB  - Among sarcomeric muscles the cardiac muscle cells are unique by, inter alia, a
      systemic and extended cell-cell contact structure, the intercalated disk (ID),
      comprising frequent and closely spaced arrays of plaque-coated cell-cell adhering
      junctions (AJs). As some of these junctions may look somewhat like desmosomes and
      others like fasciae adhaerentes, the dogma has emerged in the literature that IDs
      contain - like epithelial cells - both kinds of AJs formed by - for the most -
      mutually exclusive molecular ensembles. This, however, is not the case. In
      comprehensive immunoelectron microscopic studies of mammalian (human, bovine,
      rat, mouse) and non-mammalian (chicken, amphibia, fishes) heart muscle tissues,
      we have localized major constituents of the desmosomal plaques of polar
      epithelia, desmoplakin, plakophilin-2 and plakoglobin, as well as the desmosomal
      cadherins, desmoglein Dsg2 and desmocollin Dsc2, in both kinds of ID AJs,
      independent of the specific morphological appearance. The desmosomal molecules
      are not restricted to the desmosome-like-looking junctions but can also be
      detected in junctions appearing similar to the zonula or fascia adhaerens
      structures. These AJs of cardiac ID are therefore subsumed under the collective
      term area composita. We discuss our results with respect to the importance of ID
      junction molecules for the formation, maintenance and function of the heart,
      particularly in relation to recent findings that deletions of - or mutations in -
      genes encoding such proteins can cause severe, sometimes lethal damages.

PMID- 16406611
TI  - Game-related seizures presenting with two types of clinical features.
AB  - We evaluated 22 patients with epileptic seizures in which the seizures were
      triggered by various games or game-related materials. Based on whether
      spontaneous seizure coexisted or not, these 22 patients were divided into two
      groups. Ten patients who experienced seizures exclusively while playing or
      watching specific games were referred to as Group I, while 12 patients that had
      both game-induced and spontaneous seizures were classified as Group II. The
      patients in Group I had a middle-age onset (39.1 years) with a male predominance
      (90%). The electroencephalogram (EEG) or brain magnetic resonance imaging
      revealed non-specific abnormalities in 60%, and the partial onset seizure was
      recognized in 30% of patients. Antiepileptic drugs had uncertain benefits in this
      group. In Group II, patients had a male predominance (67%), with onset during
      adolescence (16.3 years). Most of them had generalized tonic-clonic seizures,
      myoclonic seizures, and absences, and 42% showed epileptiform discharge on EEG.
      These 12 patients were categorized into idiopathic generalized epilepsies.
      Although photosensitivity was an important factor, higher mental activity seemed
      to be significant precipitants of seizures in Group II. Antiepileptic drugs were
      necessary and valproic acid alone or combined with clonazepam was effective in
      this group. The results showed that game-related seizures are not a unique and
      homogeneous syndrome and may consist of different mechanisms. Teenage onset,
      coexistent spontaneous seizure, and associated idiopathic generalized epilepsies
      were crucial factors in the determination of antiepileptic drug therapy.
      Moreover, avoiding the related games altogether may be a more productive
      preventive measure.

PMID- 16406612
TI  - Synthesis, X-ray crystallographic analysis, and antitumor activity of N
      (benzothiazole-2-yl)-1-(fluorophenyl)-O,O-dialkyl-alpha-aminophosphonates.
AB  - Alpha-aminophosphonates containing benzothiazole and fluorine moiety, 4a-4m, were
      synthesized by Mannich-type addition in ionic liquid media with high yield and
      short reaction time. Their structures were established by IR, (1)H NMR, (13)C
      NMR, and elemental analysis. The X-ray crystallographic data of compounds 4j and
      4m were provided. The newly synthesized compounds were evaluated for their
      anticancer activities against PC3, A431, A375, and Bcap37 cells in vitro by the
      MTT method. Compound 4c is highly effective against PC3 cells and moderate to
      A431 cells. Hence, further study is necessary to find out the potential antitumor
      activities.

PMID- 16406613
TI  - Imidazo[1,2-a]pyrimidines as functionally selective GABA(A) ligands.
AB  - Imidazo[1,2-a]pyrimidines are GABA(A) receptor benzodiazepine binding site
      ligands which can exhibit functional selectivity for the alpha(3) subtype over
      the alpha(1) subtype. SAR studies to optimize this functional selectivity are
      described.

PMID- 16406614
TI  - Studies on cleavage of DNA by N-phosphoryl branched peptides.
AB  - It was found that Nalpha,Nepsilon-di[N-(O,O-diisopropyl)phosphoryl-L-leucy]-L
      lysyl-methyl ester (1) and Nalpha,Nepsilon-di[N-(O,O-diisopropyl)phosphoryl-L
      phenylalanyl]-L-lysyl-methyl ester (2) could cleave supercoiled DNA such as PUC19
      efficiently in 40 mM Britton-Robinson buffer. The cleavage activities for both
      were investigated by agarose gel electrophoresis. The T4 ligase experiments
      implied that the cleavage of DNA occurs via a hydrolytic path. The results showed
      that the cleavage reaction of DNA is dependent on the value of pH and ionic
      strength in the solution. DNA cleavage is more efficient by N-phosphoryl branched
      peptide 2 than by N-phosphoryl branched peptide 1. The experiments also show that
      hydrolysis of DNA by N-phosphoryl branched peptide 1 was accelerated in the
      presence of Mg2+ or Zn2+ ions. The interactions of DNA with N-phosphoryl branched
      peptides were also characterized by melting temperature measurements and circular
      dichroism (CD) techniques. On the basis of experimental data, the possible
      mechanism of interactions between DNA with N-phosphoryl branched peptides was
      discussed.

PMID- 16406615
TI  - Cloning and characterization of a third isoform of corazonin in the honey bee
      Apis mellifera.
AB  - The precursor of the insect hormone corazonin has been cloned from the honey bee
      Apis mellifera. The precursor predicts a novel isoform of corazonin,
      pQTFTYSHGWTNamide, which was confirmed by tandem mass spectrometry. Although Apis
      corazonin differs only by a glutamine/threonine substitution from [His7]
      corazonin, it is considerably less active in the dark color inducing assay on
      albino locusts. Whole mount fluorescence immunohistochemistry of the central
      nervous system of the honey bee showed a pattern similar to the ones described
      for other insects. Four neurons of the lateral protocerebrum project axons
      towards the retrocerebral complex. It is unlikely that Apis corazonin is present
      in all hymenopteran species since the presence of this peptide could not be
      demonstrated by means of mass spectrometry in the retrocerebral complex of the
      red wood ant Formica rufa and the wasp Vespula saxonica. Instead, we found masses
      corresponding with [Arg7]- and [His7]-corazonin respectively, suggesting that
      some of the corazonin isoforms originated late during evolution in different
      insect orders.

PMID- 16406616
TI  - Comparison of four techniques for the fixation of a collagen scaffold in the
      human cadaveric knee.
AB  - OBJECTIVE: Four fixation techniques for a fibrinogen and thrombin coated collagen
      fleece, used as a scaffold in the cartilage repair, were compared simulating the
      initial postoperative period in the cadaveric knee joints. METHODS: Full
      thickness chondral lesions were made on the medial femoral condyles of seven
      human cadaveric inferior extremities. Four scaffolds without seeded chondrocytes
      were implanted into each lesion using four fixation techniques consecutively:
      self-adhesion without additional material (SA), fibrin sealant (FS), bone sutures
      (BS), and periosteal cover (PC). After each implantation 150 cycles of continuous
      passive motion (CPM) were performed. Two cases were additionally exposed to 50
      cycles of 10 and 20 kg loading each after the completion of CPM. The scaffolds
      were evaluated after every 30 cycles, and the fixation strength was tested after
      the motion was completed. RESULTS: All the SA scaffolds were detached before 60
      cycles. The other scaffolds remained stable throughout the testing with only
      minor disruptions. The endpoint fixation strength was higher for BS and PC than
      for the FS scaffolds. The FS scaffolds were detached as a result of additional
      load cycles, while the BS and PC scaffolds showed substantial deformations.
      CONCLUSION: SA of tested scaffold did not provide sufficient fixation. The FS
      fixation was easy to perform and assured satisfactory scaffold stability. BS and
      PC provided excellent scaffold stability, but the techniques were difficult and
      caused additional injuries. Regardless of the fixation technique used, the tested
      collagen scaffold may not be exposed to loading in the initial postoperative
      period.

PMID- 16406617
TI  - Here come the SUNs: a nucleocytoskeletal missing link.
AB  - The nuclear envelope has traditionally been thought of as a barrier that
      separates the nucleoplasm from the cytoplasm in eukaryotic cells. Increasing
      evidence shows that the nuclear envelope also links the inside of the nucleus to
      the cytoskeleton. Here we discuss recent papers showing that this link occurs
      through complexes of lamins on the inner aspect of the inner nuclear membrane,
      transmembrane proteins of the inner nuclear membrane called SUNs and large
      nesprin isoforms localized specifically to the outer nuclear membrane. These
      discoveries have implications for nuclear positioning, nuclear migration and
      pathogenesis of inherited diseases that are caused by mutations in nuclear
      envelope proteins.

PMID- 16406618
TI  - Pre-registration student nurses perception of the hospital-learning environment
      during clinical placements.
AB  - If we subscribe to the notion that nursing is an action profession, that nurses
      learn by doing [Neary, M., 2000. Responsive assessment: assessing student nurses'
      clinical competence. Nurse Education Today 21, 3-17], then the mastery of
      fundamental clinical skills must be a key component of courses leading to
      registration. The last two decades have seen widespread changes to nurse
      education but the clinical field remains an invaluable resource in preparing
      students for the reality of their professional role supporting the integration of
      theory and practice and linking the 'knowing what' with the 'knowing how'. The
      clinical-learning environment represents an essential element of nurse education
      that needs to be measurable and warrants further investigation. This exploratory
      cohort study (n = 67) examined pre-registration student nurses' perception of the
      hospital-learning environment during clinical placements together with the key
      characteristics of the students' preferred learning environment utilising an
      established tool, the clinical-learning environment inventory (CLEI) tool [Chan,
      D., 2001a. Development of an innovative tool to assess hospital-learning
      environments. Nurse Education Today 21, 624-631; Chan, D., 2001b. Combining
      qualitative and quantitative methods in assessing hospital-learning environments.
      International Journal of Nursing Studies 3, 447-459]. The results demonstrated
      that in comparison with the actual hospital environment, students would prefer an
      environment with higher levels of individualisation, innovation in teaching and
      learning strategies, student involvement, personalisation and task orientation.

PMID- 16406619
TI  - The Turkish version of the Omaha System: its use in practice-based family nursing
      education.
AB  - The aims of this manuscript are to examine the validity and reliability of the
      Turkish version of the Omaha System, and to demonstrate its effectiveness as a
      tool for nursing education. In this methodological and descriptive study, seventy
      students attending a training program used the Omaha System in clinical practice
      settings for assessing health problems of 157 clients and for nursing
      interventions during 378 home visits. After the system's adaptation to the
      Turkish language, its content validity was reconfirmed through feedback from the
      students and interrater reliability was tested on six independent students with
      kappa statistics. The reliability scores were at a statistically significant
      level when coding the records using the Omaha System. Clinical practice was
      explained with 332 problems and 1783 nursing intervention terms. Study findings
      indicate several strengths, including high reliability - except in target terms,
      coding of problems and interventions, improved understanding of the course, as
      well as some limitations: the need for new terms and more time required for
      manual documentation. The findings of the study supported the usefulness of the
      Omaha System in describing the practice of community health nursing.

PMID- 16406620
TI  - Stakeholder views of the training needs of an interprofessional practitioner who
      works with older people.
AB  - This paper, reports on United Kingdom research to examine the education and
      training requirements of an interprofessional practitioner for older people. The
      research was part of a larger study, funded by a local Workforce Development
      Confederation to identify whether there is a need for an interprofessional
      practitioner, and if so, determine their role and training requirements. Views of
      clients, carers and service providers were elicited using multiple methods
      including interviews, focus groups and questionnaires. The majority of service
      providers identified the need for an interprofessional practitioner and confirmed
      that these staff already exist within many multi-disciplinary community teams.
      The range of educational needs identified reflects the understanding that
      rehabilitation for older people requires a broad spectrum of knowledge and skills
      that cover both 'health' and 'social' needs. It was felt that education and
      training should be established and accredited at a national level, with a career
      structure and appropriate recognition of the interprofessional role. Clients and
      carers identified unmet needs and want a 'Jack of all trades' who will complement
      the existing workforce. They recommended that recognised qualifications would
      provide interprofessional workers with 'status' and therefore acceptance by other
      professionals. This paper, discusses the implications of the stakeholder views on
      interprofessional education and training.

PMID- 16406621
TI  - An exploration of on-line access by non-traditional students in higher education:
      a case study.
AB  - The nature of Higher Education (HE) has seen many changes throughout the last
      decade. The agenda for widening participation in HE has led to an increase in the
      number of students with a broader range of educational backgrounds. At the same
      time there has been a surge in the development of digitalisation and the
      convergence of computing and telecommunications technologies available for use in
      education. This paper discusses the outcomes of a case study, conducted in a
      School of Health Studies within a northern English University, which identified
      the extent to which 'non-traditional' students access on-line learning
      facilities, such as virtual learning environments and library networks, and what
      factors enhanced or formed barriers to access. 'Non-traditional' students, for
      the purpose of this study, were defined as mature students who were returning to
      higher education after a considerable break. The outcomes indicated that skill
      deficit is a major obstacle for many 'non-traditional' students. The paper
      explores this issue in depth and suggests potential ways forward for the delivery
      of technology supported learning for 'non-traditional' students in Higher
      Education.

PMID- 16406622
TI  - Inhibition of benzo(a)pyrene-induced cell cycle progression by all-trans retinoic
      acid partly through cyclin D1/E2F-1 pathway in human embryo lung fibroblasts.
AB  - Benzo(a)pyrene [B(a)P] is a potent environmental carcinogen, which induces cell
      cycle changes. All-trans retinoic acid (ATRA) is a promising agent in prevention
      and treatment of human cancers. In the present study, we investigated the
      inhibition of B(a)P-induced cell cycle progression by ATRA in human embryo lung
      fibroblast (HELF). Our results showed that after treatment with B(a)P, the
      expression of cyclin D1 and E2F-1 were both increased significantly in HELF.
      There were almost no changes of CDK4 and E2F-4 expression by treatment with
      B(a)P. As expected, pretreatment with ATRA could efficiently decrease B(a)P
      induced overexpression of cyclin D1 and E2F-1. In a further study, we stably
      transfected antisense cyclin D1 and antisense CDK4 plasmid into HELF. The
      inhibition of cyclin D1 expression and the inhibition of CDK4 expression
      significantly impaired the B(a)P-induced overexpression of E2F-1 respectively.
      Pretreatment with ATRA, cells expressing antisense cyclinD1 or antisense CDK4
      showed a lesser decrease of B(a)P-induced overexpression of E2F-1 compared with
      similarly treated HELF. Furthermore, flow cytometry analysis showed that B(a)P
      promoted cell cycle progression from G(1) phase to S phase, while pretreatment
      with ATRA could inhibit B(a)P-induced cell cycle progression by an accumulation
      of cells in the G(1) phase. It was suggested that ATRA could block B(a)P-induced
      cell cycle promotion partly through the cyclin D1/E2F-1 pathway in HELF.

PMID- 16406623
TI  - Effects of abdominal muscle fatigue on anticipatory postural adjustments
      associated with arm raising.
AB  - Anticipatory postural adjustments (APAs) are postulated to ameliorate the effects
      of the disturbance to posture caused by voluntary movement. The primary
      hypothesis tested in our study was that the magnitude of anticipatory trunk
      muscle activity is altered by abdominal muscle fatigue. A subsidiary aim of the
      present study was to examine the directional nature of APAs and use this
      information to elucidate the central or peripheral nature of changes in postural
      muscle activity associated with abdominal muscle fatigue. The present study was a
      within subject design, where abdominal muscle fatigue was induced by a static
      abdominal curl. Surface EMG was used to assess postural muscle activity in the
      following trunk muscles; rectus abdominis, erector spinae and internal oblique.
      Following abdominal muscle fatigue, the magnitude of muscle activity during APAs
      was significantly reduced by 20% in both the rectus abdominis (fatigued muscle)
      and the erector spinae (not fatigued) indicating a central rather than peripheral
      fatigue effect on muscle activity. Abdominal muscle fatigue also induced a 30%
      increase in the baseline muscle activity of the internal oblique. The changes in
      magnitude of APA muscle activity may reflect a change in system gain or a change
      in postural control perhaps related to a change in perceived postural stability.
      An increase in baseline muscle activity in the internal oblique may compensate
      partially for the reduction in APAs.

PMID- 16406625
TI  - Predicting Gran alkalinity and calcium concentrations in river waters over a
      national scale using a novel modification to the G-BASH model.
AB  - Monthly stream water calcium and Gran alkalinity concentration data from 11 sub
      catchments of the Nether Beck in the English Lake District have been used to
      appraise the transferability of the Scottish, River Dee-based G-BASH model.
      Readily available riparian zone geochemistry and flow paths were used initially
      to predict minimum and mean stream water concentrations at the Nether Beck, based
      on calibration equations from the River Dee catchment data. Predicted values
      significantly exceeded observed values. Differences in runoff between the two
      areas, leading to a dilution effect in the Nether Beck, explained most of the
      difference between observed and predicted values. Greater acid deposition in the
      Lake District also reduced stream water Gran alkalinity concentrations in that
      area. If regional differences in precipitation, evapotranspiration and pollutant
      deposition are incorporated into the model, it may then be used reliably to
      predict catchment susceptibility to acidification over a wide regional (national)
      scale.

PMID- 16406624
TI  - Impact of river overflowing on trace element contamination of volcanic soils in
      south Italy: part II. Soil biological and biochemical properties in relation to
      trace element speciation.
AB  - The effect of heavy metal contamination on biological and biochemical properties
      of Italian volcanic soils was evaluated in a multidisciplinary study, involving
      pedoenvironmental, micromorphological, physical, chemical, biological and
      biochemical analyses. Soils affected by recurring river overflowing, with Cr(III)
      contaminated water and sediments, and a non-flooded control soil were analysed
      for microbial biomass, total and active fungal mycelium, enzyme activities (i.e.,
      FDA hydrolase, dehydrogenase, beta-glucosidase, urease, arylsulphatase, acid
      phosphatase) and bacterial diversity (DGGE characterisation). Biological and
      biochemical data were related with both total and selected fractions of Cr and Cu
      (the latter deriving from agricultural chemical products) as well as with total
      and extractable organic C. The growth and activity of soil microbial community
      were influenced by soil organic C content rather than Cu or Cr contents. In fact,
      positive correlations between all studied parameters and organic C content were
      found. On the contrary, negative correlations were observed only between total
      fungal mycelium, dehydrogenase, arylsulphatase and acid phosphatase activities
      and only one Cr fraction (the soluble, exchangeable and carbonate bound).
      However, total Cr content negatively affected the eubacterial diversity but it
      did not determine changes in soil activity, probably because of the redundancy of
      functions within species of soil microbial community. On the other hand,
      expressing biological and biochemical parameters per unit of total organic C, Cu
      pollution negatively influenced microbial biomass, fungal mycelium and several
      enzyme activities, confirming soil organic matter is able to mask the negative
      effects of Cu on microbial community.

PMID- 16406626
TI  - A comparison of Cu, Pb, As, Cd, Zn, Fe, Ni and Mn determined by acid
      extraction/ICP-OES and ex situ field portable X-ray fluorescence analyses.
AB  - Total concentrations of Cu, Pb, As, Cd, Zn, Fe, Ni and Mn were determined for 81
      soil samples using two types of field portable X-ray fluorescence (FPXRF) system;
      dual isotope and X-ray tube. FPXRF metal concentrations were statistically
      compared with analytical results from aqua regia extractions followed by
      Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) analysis. The
      ability of each FPXRF instrument to produce analytical results comparable to the
      reference method was assessed by linear regression. A high degree of linearity
      was found for Fe and Pb with the X-ray tube instrument and for Fe, Cu, Pb, Zn, Cd
      and Mn with the dual source instrument. FPXRF analyser performance improved with
      increased analysis time for Cu, Mn and Pb, whilst Fe, Zn, Cd, Ni and As showed no
      significant improvement. Particle size did not influence FPXRF analyser
      performance. Both the dual isotope and the X-ray tube FPXRF instruments are
      effective tools for rapid, quantitative assessment of soil metal contamination
      and for monitoring the efficacy of remediation strategies.

PMID- 16406627
TI  - Selective refocusing pulses in magic-angle spinning NMR: characterization and
      applications to multi-dimensional protein spectroscopy.
AB  - Band-selective pulses are frequently used in multi-dimensional NMR in solution,
      but have been used relatively less often in solid-state NMR applications because
      of the complications imposed by magic-angle spinning. In this work, we examine
      the frequency profiles and the refocusing efficiency of several commonly employed
      selective general rotation pi pulses through experiments and numerical
      simulations. We demonstrate that highly efficient refocusing of transverse
      magnetization can be achieved, with experiments that agree well with numerical
      simulations. We also show that the rotational echo is shifted by a half rotor
      period if a selective pulse is applied over an integer number of rotor periods.
      Appropriately synchronizing indirect evolution periods with selective pulses
      ensures proper phasing of cross peaks in 2D spectra. The improved performance of
      selective pulses in multi-dimensional protein spectroscopy is demonstrated on the
      56-residue beta1 immunoglobulin binding domain of protein G (GB1).

PMID- 16406628
TI  - Effect of impermeable boundaries on diffusion-attenuated MR signal.
AB  - The nonlinear dependence between the logarithm of the diffusion weighted signal,
      lnS, and the b-value, b, has often been interpreted as a manifestation of two
      physically distinct compartments, resulting in a biexponential form of the
      signal. This model fits to experimental data, however, has failed to yield
      realistic compartment sizes, severely jeopardizing the use of DWI to infer
      structural information on a cellular level. It has been hypothesized that the
      biexponential behavior can be attributed to the effect of confining boundaries
      that restrict diffusion in individual physical compartments. This interpretation
      is based on the analysis of diffusion in the presence of impermeable interfaces
      for short diffusion times such that the layer in which diffusion is affected by
      the boundary is thin as compared with the dimensions of the whole compartment.
      This model system is analyzed from the point of view of the cumulant expansion of
      the diffusion-weighted signal that results in a Taylor expansion of lnS in powers
      of b. Termination of this expansion to a polynomial form provides an excellent
      accuracy for small b-factors, but the series diverges for large b. The
      convergence of the series is studied, yielding a large range of b-values in which
      the absolute error of terminating the series at the second term remains smaller
      than 1% relative to the signal magnitude without diffusion weighting. With this
      accuracy, the signal in the studied model can be described as lnS approximately 
      A.bD+B.(bD)2, where the parameters A and B can be expressed in terms of
      correlation functions of molecular velocity. Fitting of these parameters to the
      exact signal is more stable than for the three parameters of the biexponential
      function. This description fails for large b, for which the cumulant expansion
      diverges. The signal at even larger b-values is proportional to 1/b, 1/b3/2, and
      1/b2 in one-, two-, and three-dimensional systems, respectively.

PMID- 16406629
TI  - Quorum sensing: dynamic response of Pseudomonas aeruginosa to external signals.
AB  - A recent study suggests that the opportunistic pathogen Pseudomonas aeruginosa
      can actively monitor the host immune system. The P. aeruginosa outer membrane
      protein OprF was found to bind specifically to the cytokine interferon-gamma (IFN
      gamma), and this interaction upregulated production of virulence factors through
      a cell-cell communication system known as quorum sensing (QS). Taken together
      with previous findings that P. aeruginosa QS can alter the host immune response
      (e.g. by activation of IFN-gamma), these data illustrate an exciting new element
      of bacteria-host interactions in which the P. aeruginosa quorum-sensing system
      both senses and modulates the host immune state.

PMID- 16406630
TI  - Lack of cross-reactivity between the Bacillus thuringiensis derived protein Cry1F
      in maize grain and dust mite Der p7 protein with human sera positive for Der p7
      IgE.
AB  - Cry1F protein, derived from Bacillus thuringiensis, is effective at controlling
      lepidopteran pests and a synthetic Cry1F transgene was transferred into maize.
      For the safety assessment of genetically modified food crops, the allergenic
      potential of the introduced novel trait(s) is evaluated. Because no single
      parameter is currently predictive of allergic potential, a 'weight of evidence'
      approach has been proposed. As part of this assessment, the amino acid (aa)
      sequence of the Cry1F protein was compared to a database of known allergens using
      recommended criteria. The Cry1F protein did not show significant similarity or a
      match of eight contiguous identical aa with any allergen. However, a single six
      contiguous aa match was identified between Cry1F and the Der p7 protein of the
      dust mite, Dermatophagoides pteronyssinus. To investigate whether Cry1F was cross
      reactive with Der p7, sera from 10 dust mite allergic patients containing Der p 7
      specific IgE antibody were used to compare IgE-specific binding. No evidence of
      cross-reactivity was observed between Cry1F and Der p7. This study provides in
      vitro IgE sera screening data, that when considered in the context of other
      bioinformatic data [Hileman R.E., Silvanovich, A., Goodman R.E., Rice E.A.,
      Holleschak G., Astwood J.D., Hefle S.L., 2002. Bioinformatic methods for
      allergenicity assessment using a comprehensive allergen database. Int. Arch.
      Allergy Immunol. 128, 280-291; Stadler, M.B., Stadler, B.M., 2003. Allergenicity
      prediction by protein sequence. FASEB J. 17, 1141-1143.], adds further evidence
      arguing against the use of a six contiguous identical amino acid search to
      identify potential cross-reactive allergens. Cry1F is heat labile, rapidly
      hydrolyzed in an in vitro pepsin resistance assay, not glycosylated and not from
      an allergenic source. Taken together, these data indicate a lack of allergenic
      concern for Cry1F.

PMID- 16406631
TI  - Increase of peroxisome proliferator-activated receptor delta gene expression in
      the lungs of streptozotocin-induced diabetic rats.
AB  - Peroxisome proliferator-activated receptors (PPARs) play key roles in the
      regulation of energy homeostasis and inflammation while the agonists of PPARalpha
      and PPARgamma are recently used for therapy in clinic. However, functions of
      PPARdelta are still unclear. In the present study, we investigated the changes of
      PPARdelta gene expression in the lung of diabetic rats. The mean level of mRNA
      transcripts encoding PPARdelta was increased in the lung isolated from
      streptozotocin-induced diabetic rats (STZ-diabetic rats) to about 1.6-fold of
      that in normal rats. Exogenous insulin at the dose sufficient to normalize the
      plasma glucose of STZ-diabetic rats reversed the mRNA level of PPARdelta in lungs
      after a 4-day treatment. Similar results were also observed in STZ-diabetic rats
      that received the treatment of phlorizin to reverse the plasma glucose level for
      4 days. Otherwise, the protein level of PPARdelta was higher in the lung of STZ
      diabetic rats than that in normal rats. Treatment with exogenous insulin or
      phlorizin reversed this elevated protein level of PPARdelta in the lung of STZ
      diabetic rats to near the normal level. The obtained results suggest that
      increase of plasma glucose is responsible for the higher gene expression of
      PPARdelta in the lung of STZ-diabetic rats.

PMID- 16406632
TI  - Predicting physical activity intention and behaviour among children in a
      longitudinal sample.
AB  - We examined predictors of leisure-time physical activity intention and behaviour
      in children, and the potential direct and moderating effects of gender and
      ethnicity. Participants were 364 (230 Asian; 134 Caucasian) 9-11-year-old
      children who completed measures of the theory of planned behaviour (TPB) and
      physical activity behaviour (Physical Activity Questionnaire for Children) across
      three, 3-month intervals (i.e., two prediction time-periods) in Canada. The TPB
      explained 35-50% of the variance in physical activity behaviour and 74-76% of the
      variance in intention using structural equation modelling. An autoregressive
      longitudinal path model showed that the TPB predicted changes in physical
      activity and physical activity predicted changes in TPB constructs (p<.05).
      Overall, intention and perceived behavioural control were significant (p<.05)
      contributors to the direct prediction of behaviour and subjective norm and
      perceived behavioural control were significant (p<.05) predictors of intention.
      Gender did not show a robust relationship with physical activity or intention,
      but the effect of ethnicity on physical activity was mediated through perceived
      behavioural control (Asians less active than Caucasians). Finally, gender and
      ethnicity did not moderate TPB and physical activity relations (p<.05). These
      data suggest that childhood may be a formative stage for the development of
      physical activity cognitions and that promoting physical activity in children may
      require normative and control-based intervention.

PMID- 16406633
TI  - Disseminating structural genomics data to the public: from a data dump to an
      animated story.

PMID- 16406634
TI  - Stealth and mimicry by deadly bacterial toxins.
AB  - Diphtheria toxin and exotoxin A are well-characterized members of the ADP
      ribosyltransferase toxin family that function as virulence factors in the
      pathogenic bacteria Corynebacterium diphtheriae and Pseudomonas aeruginosa.
      Recent high-resolution structural data of the Michaelis (enzyme-substrate)
      complex of the P. aeruginosa toxin with an NAD(+) analog and eukaryotic
      elongation factor 2 (eEF2) have provided insights into the mechanism of
      inactivation of protein synthesis caused by these protein factors. In addition,
      rigorous steady-state and stopped-flow kinetic analyses of the toxin-catalyzed
      reaction, in combination with inhibitor studies, have resulted in a quantum leap
      in our understanding of the mechanistic details of this deadly enzyme mechanism.
      It is now apparent that these toxins use stealth and molecular mimicry in
      unleashing their toxic strategy in the infected host eukaryotic cell.

PMID- 16406635
TI  - Regulating the regulator: negative regulation of Cbl ubiquitin ligases.
AB  - Cbl proteins are regulators of signal transduction through many pathways and,
      consequently, regulate cell function and development. They are ubiquitin ligases
      that ubiquitinate and target many signaling molecules for degradation. The Cbl
      proteins themselves are regulated by an increasingly complex network of
      interactions that fine-tune the effects that Cbl proteins have on signaling. The
      negative regulation of Cbl protein function can occur via cis-acting structural
      elements that prevent inappropriate ubiquitin ligase activity, degradation of the
      Cbl proteins, inhibition without degradation owing to interaction with other
      signaling proteins, deubiquitination of Cbl substrates, and regulation of
      assembly of the endosomal ESCRT-I complex. Defects in the regulatory mechanisms
      that control Cbl function are implicated in the development of immunological and
      malignant diseases.

PMID- 16406636
TI  - Telomere dynamics in genome stability.
AB  - The past several years have seen an increasing interest in telomere
      recombinational interactions that provide many functions in telomere capping, in
      telomere size homeostasis and in overcoming the catastrophic effects of
      telomerase deficiency. Several key recombination mechanisms have emerged from
      recent investigations. In the yeasts, these mechanisms include exchange between
      subtelomeric regions and telomere sequences, rapid telomere expansion and
      telomere deletion. These processes proceed by pathways that use both the cellular
      recombination machinery and novel mechanisms such as rolling circle replication.
      The insights gained from recent studies extend our understanding of similar
      processes in higher eukaryotes and suggest that the recombinational dynamics of
      telomeres have additional roles that contribute to genomic stability and
      instability.

PMID- 16406637
TI  - Prototype-distortion category learning: a two-phase learning process across a
      distributed network.
AB  - This paper reviews a body of work conducted in our laboratory that applies
      functional magnetic resonance imaging (fMRI) to better understand the biological
      response and change that occurs during prototype-distortion learning. We review
      results from two experiments (Little, Klein, Shobat, McClure, & Thulborn, 2004;
      Little & Thulborn, 2005) that provide support for increasing neuronal efficiency
      by way of a two-stage model that includes an initial period of recruitment of
      tissue across a distributed network that is followed by a period of increasing
      specialization with decreasing volume across the same network. Across the two
      studies, participants learned to classify patterns of random-dot distortions
      (Posner & Keele, 1968) into categories. At four points across this learning
      process subjects underwent examination by fMRI using a category-matching task. A
      large-scale network, altered across the protocol, was identified to include the
      frontal eye fields, both inferior and superior parietal lobules, and visual
      cortex. As behavioral performance increased, the volume of activation within
      these regions first increased and later in the protocol decreased. Based on our
      review of this work we propose that: (i) category learning is reflected as
      specialization of the same network initially implicated to complete the novel
      task, and (ii) this network encompasses regions not previously reported to be
      affected by prototype-distortion learning.

PMID- 16406638
TI  - Cognitive neuroimaging: cognitive science out of the armchair.
AB  - Cognitive scientists were not quick to embrace the functional neuroimaging
      technologies that emerged during the late 20th century. In this new century,
      cognitive scientists continue to question, not unreasonably, the relevance of
      functional neuroimaging investigations that fail to address questions of interest
      to cognitive science. However, some ultra-cognitive scientists assert that these
      experiments can never be of relevance to the study of cognition. Their reasoning
      reflects an adherence to a functionalist philosophy that arbitrarily and
      purposefully distinguishes mental information-processing systems from brain or
      brain-like operations. This article addresses whether data from properly
      conducted functional neuroimaging studies can inform and subsequently constrain
      the assumptions of theoretical cognitive models. The article commences with a
      focus upon the functionalist philosophy espoused by the ultra-cognitive
      scientists, contrasting it with the materialist philosophy that motivates both
      cognitive neuroimaging investigations and connectionist modelling of cognitive
      systems. Connectionism and cognitive neuroimaging share many features, including
      an emphasis on unified cognitive and neural models of systems that combine
      localist and distributed representations. The utility of designing cognitive
      neuroimaging studies to test (primarily) connectionist models of cognitive
      phenomena is illustrated using data from functional magnetic resonance imaging
      (fMRI) investigations of language production and episodic memory.

PMID- 16406640
TI  - Temperature and the respiratory properties of whole blood in two reptiles, Pogona
      barbata and Emydura signata.
AB  - We investigated the capacity of two reptiles, an agamid lizard Pogona barbata and
      a chelid turtle Emydura signata, to compensate for the effects of temperature by
      making changes in their whole blood respiratory properties. This was accomplished
      by measuring the P50 (at 10, 20 and 30 degrees C), hematocrit (Hct), haemoglobin
      concentration ([Hb]) and mean cell haemoglobin concentration (MCHC) in field
      acclimatised and laboratory acclimated individuals. The acute effect of
      temperature on P50 in P. barbata, expressed as heat of oxygenation (deltaH),
      ranged from -16.8+/-1.84 to -28.5+/-2.73 kJ/mole. P50 of field acclimatised P.
      barbata increased significantly from early spring to summer at the test
      temperatures of 20 degrees C (43.1+/-1.2 to 48.8+/-2.1 mmHg) and 30 degrees C
      (54.7+/-1.2 to 65.2+/-2.3 mmHg), but showed no acclimation under laboratory
      conditions. For E. signata, deltaH ranged from -31.1+/-6.32 to -48.2+/-3.59
      kJ/mole. Field acclimatisation and laboratory acclimation of P50 did not occur.
      However, in E. signata, there was a significant increase in [Hb] and MCHC from
      early spring to summer in turtles collected from the wild (1.0+/-0.1 to 1.7+/-0.2
      mmol/L and 4.0+/-0.3 to 6.7+/-0.7 mmol/L, respectively).

PMID- 16406639
TI  - Lysine deficiency and feed restriction independently alter cationic amino acid
      transporter expression in chickens (Gallus gallus domesticus).
AB  - The effect of a lysine-deficient diet on cationic amino acid transporter (CAT1-3)
      mRNA expression was determined in broiler chickens. Chicks consumed a lysine
      adequate (LA; 1.3% lysine) or lysine-deficient (LD; 0.7% lysine) diet. Pair-fed
      chicks consumed the LA diet in an amount equal to that consumed by LD chicks
      during the previous day (PLA). CAT 1-3 mRNA expression in the liver, pectoralis
      and bursa of LD chicks were lower than that of LA and PLA chicks (P<0.05), and
      levels were not detectable in LD chick thymus. High affinity CAT mRNA expression
      in isolated bursacytes was 16-fold higher in LD chicks than that of LA chicks
      (P<0.001). Thymocyte high affinity CAT mRNA expression was 5-fold lower than that
      of LA chicks (P<0.05). The summed amount of high affinity CAT-1 and CAT-3 mRNA
      expression in chicks fed a lysine adequate diet was highly correlated (r2=0.51;
      P<0.001) to a tissue's growth during a lysine deficiency or feed restriction. In
      the thymus and bursa of LD chicks, CAT mRNA levels differed between resident
      lymphocytes and their surrounding tissues. By expressing high affinity CAT
      isoforms, developing lymphocytes may have a greater ability to obtain lysine than
      their surrounding tissue during a lysine deficiency.

PMID- 16406641
TI  - Expressed sequence tags from eyestalk of kuruma prawn, Marsupenaeus japonicus.
AB  - We analyzed the expressed sequence tags (ESTs) obtained from a cDNA library of
      the eyestalk of the kuruma prawn, Marsupenaeus japonicus, to examine gene
      expression profile with special focus on female reproduction. The assembly of
      1988 ESTs created 136 contigs from 738 ESTs; however 1250 ESTs remained
      singletons. Significant similarities (blast score > or = 50 bits) to the DNA
      sequences in the databank were found for only 16.7% of the 1386 sequences (136
      contigs plus 1250 singletons), suggesting that the eyestalk library contains many
      unknown genes. Ribosomal RNA and mitochondrial respiration enzymes with
      significant similarities were found abundantly in the ESTs, whereas genes related
      to maturation or endocrine systems were scarce. Three ESTs were assumed to encode
      novel eyestalk hormones with marked similarities to pigment-dispersing hormone,
      molt-inhibiting hormone and crustacean hyperglycemic hormone. Sequences encoding
      a product highly homologous to farnesoic acid O-methyltransferase, an enzyme that
      produces methyl farnesoate, were also found.

PMID- 16406642
TI  - The response of the natriuretic peptide system to water deprivation in the desert
      rodent, Notomys alexis.
AB  - Natriuretic peptides (NPs) are regulatory molecules that cause cGMP-mediated
      diuresis and natriuresis in mammals. Accordingly, it is interesting to consider
      their role in desert-adapted animals in which water is often limited. This study
      investigated the response of the natriuretic peptide (NP) system to varying
      periods of water deprivation (WD) in the Australian desert rodent species,
      Notomys alexis. It was hypothesised that the expression of the NP system will be
      down-regulated in water-deprived N. alexis compared to water-replete animals. The
      plasma levels of ANP were significantly reduced after 3 days of WD, but were
      unaffected by 7, 14 and 28 days of WD. Water deprivation for 3, 7, 14 days had a
      variable effect on the mRNA expression of ANP, CNP, NPR-A, NPR-B, and NPR-C, and
      a uniform down-regulation was not observed. However, after 28 days of WD, mRNA
      expression was similar to water-replete animals, except for NPR-A. Surprisingly,
      7 and 14 days of WD caused an up-regulation in the ability of ANP to stimulate
      cGMP; this also occurred at 14 days for CNP. Taken together, the mRNA expression
      and peptide mediated guanylyl cyclase activity data after WD were in the opposite
      direction to what was predicted. Interestingly, after 28 days of WD, most
      parameters were similar to those of water-replete animals, which indicates that a
      down-regulation of the NP system is not part of the physiological response to an
      absence of free water in N. alexis.

PMID- 16406644
TI  - Synthesis and evaluation of antitubercular activity of imidazo[2,1
      b][1,3,4]thiadiazole derivatives.
AB  - A series of 2,6-disubstituted and 2,5,6-trisubstituted imidazo[2,1
      b][1,3,4]thiadiazoles were synthesized, the structures of the compounds were
      elucidated and screened for antitubercular activity against Mycobacterium
      tuberculosis H37Rv using the BACTEC 460 radiometric system, antibacterial
      activity against Escherichia coli and Bacillus cirrhosis, and antifungal activity
      against Aspergillus niger and Penicillium wortmanni. Among the tested compounds 2
      (2-furyl)-6-phenylimidazo[2,1-b][1,3,4] thiadiazole-5-carbaldehyde (6c) and (2
      cyclohexyl-6-phenylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methanol (7a) have shown
      the highest (100%) inhibitory activity. Compounds 6a, 6b, 7c, and 8a exhibited
      moderate antitubercular activity with percentage inhibition 36, 30, 15, and 20,
      respectively, at a MIC of >6.25 microg/ml.

PMID- 16406643
TI  - Synthesis, antitumor and anti-HIV activities of benzodithiazine-dioxides.
AB  - Several 8-chloro-7-R1-6-R2-3-R3-imidazo[1,2-b][1,4,2]benzodithiazine 5,5-dioxide
      derivatives (9-11, 16-19, and 21-24) have been synthesized as potential antitumor
      or anti-HIV agents. The in vitro antitumor and anti-HIV-1 activities of the
      compounds were determined in a panel of cell lines. The benzodithiazine-dioxide
      10 showed 50% growth inhibitory activity in low micromolar against most cells. It
      was particularly effective in leukemia, lung, melanoma, ovarian, and renal cancer
      cells with GI50 values of 1-2 microM. Interestingly, benzodithiazine-dioxide 16
      showed remarkable anti-HIV-1 activity with 50% effective concentration EC50 value
      of 0.94 microM and no significant cytotoxicity at 200.0 microM.

PMID- 16406645
TI  - Morphology and gelation of thermosensitive xyloglucan hydrogels.
AB  - Galactose modified xyloglucan is a thermally reversible hydrogel that is
      increasingly used in the biomedical field due to the ease of altering the
      gelation time and temperature by modifying the galactose removal ratio. However
      there is little information concerning the morphology and rheological properties
      of the hydrogel under physiological conditions. Differential scanning
      microcalorimetry (DSmicroC) showed the thermal gelation process to occur over a
      broad temperature range (5-50 degrees C). The rheological properties of the
      hydrogels were investigated as a function of concentration, temperature and ionic
      strength. The final elastic moduli of the hydrogels increased with increases in
      concentration. Isothermal rheology suggests that the gelation occurred in two
      distinct stages, which was influenced by the solution media. Scanning electron
      microscopy (SEM) was used to characterize the morphology of the xyloglucan which
      were thermally gelled at 37 degrees C. The resultant morphology was strongly
      dependent on the concentration of the hydrogel. Strong hydrogels were only
      obtained at 3 wt.% at 37 degrees C, and the morphology characterized by an open 3
      dimensional network, comprised of thin membranes. It is proposed that the first
      stage of the isothermal gelation is the formation and growth of the thin
      membranes, followed by the formation of a three dimensional network.

PMID- 16406646
TI  - Metabolic changes associated with hyperammonemia in patients with propionic
      acidemia.
AB  - Propionic acidemia is an autosomal recessive disorder caused by deficiency of
      propionyl CoA carboxylase. Affected patients can develop severe hyperammonemia,
      whose causative mechanism is unknown. In this study, we monitored changes in
      metabolic parameters associated with hyperammonemia in patients with propionic
      acidemia. Levels of ammonia were correlated with plasma levels of individual
      amino acids and carnitine and with urinary organic acids. Significance of
      correlations was determined with analysis of variance. Hyperammonemia positively
      correlated with an increase in branched-chain amino acids (leucine and
      isoleucine) and a decrease in glutamine/glutamate and esterified carnitine. The
      urinary excretion of methylcitric acid, formed by the combination of propionic
      acid with oxaloacetate from the Krebs cycle, increased while that of citric acid
      decreased with hyperammonemia. These results suggest that in propionic acidemia,
      hyperammonemia is triggered by catabolism with the accumulation of propionic acid
      derivatives. The decrease of the plasma levels of glutamine/glutamate with
      hyperammonemia in patients with propionic acidemia indicates that the mechanism
      producing hyperammonemia differs from that in urea cycle defects. The increase in
      methylcitric acid and decline in citric acid urinary excretion suggest that
      hyperammonemia in propionic acidemia might be related to inability to maintain
      adequate levels of glutamine precursors through a dysfunctional Krebs cycle.

PMID- 16406647
TI  - Succinate semialdehyde dehydrogenase deficiency does not down-regulate gamma
      hydroxybutyric acid binding sites in the mouse brain.
AB  - We investigated whether succinate semialdehyde dehydrogenase deficiency alters
      gamma-hydroxybutyric acid (GHB) receptor characteristics due to elevation of GHB
      levels in the mouse brain. The membrane homogenate binding and quantitative
      autoradiography using [3H]NCS-382 revealed no significant changes in the affinity
      (Kd), receptor density (Bmax), or displacement potency (IC50) in various brain
      regions of Aldh5a1-/- vs. Aldh5a1+/+ mice.

PMID- 16406649
TI  - Aldolase B mutations and prevalence of hereditary fructose intolerance in a
      Polish population.
AB  - We studied 28 Polish hereditary fructose intolerant (HFI) patients (26 unrelated)
      by direct sequencing of the ALDOB coding region/splice sites. Eight different
      mutations were found including two novel ones (each found in two unrelated
      individuals): c.250delC (frameshift) and c.522 C > G (p.Y174X). The most frequent
      mutation c.448 G > C (p.A150P, 67% of chromosomes) was screened for in a group of
      1049 randomly selected unrelated individuals. Eight (1:131) carriers were found
      allowing to estimate the HFI prevalence in Poland as 1:31,000.

PMID- 16406648
TI  - Serum proteomic signature for cystic fibrosis using an antibody microarray
      platform.
AB  - Antibody microarrays are a new proteomic technology, which we have developed as a
      platform for identifying a cystic fibrosis (CF)-specific serum proteomic
      signature. Serum samples from CF patients have been pooled and compared with
      equivalent pools of control sera in order to identify patterns of protein
      expression unique to CF. We find that the set of significantly differentially
      expressed proteins is enriched in protein mediators of inflammation from the
      NFkappaB signaling pathway, and in proteins that may be selectively expressed in
      CF-affected tissues such as lung and intestine. In several instances, we validate
      the data from the antibody microarrays by quantitative analysis with Reverse
      Capture Protein Microarrays. We conclude that antibody microarray technology is
      sensitive, quantitative, and robust, and can be useful as a proteomic platform to
      discriminate between sera from CF and control patients.

PMID- 16406650
TI  - Prostaglandin J2 reduces catechol-O-methyltransferase activity and enhances
      dopamine toxicity in neuronal cells.
AB  - There is clear evidence that an inflammatory reaction is mounted within the CNS
      following trauma, stroke, infection and seizures, thus augmenting brain damage.
      Furthermore, chronic inflammation of the CNS is implicated in many
      neurodegenerative disorders. However, the effects of products of inflammation on
      neuronal cells are poorly understood. Herein, we characterize the effects of a
      neurotoxic product of inflammation, prostaglandin J2 (PGJ2), on catechol-O
      methyltransferase (COMT) in human dopaminergic-like neuroblastoma SK-N-SH cells
      and rat (P2) cortical neurons. COMT metabolizes catechols and catecholamines, a
      pathway relevant to neurodegeneration. PGJ2 treatment reduced the expression and
      activity of COMT, induced its sequestration into perinuclear aggregates and
      potentiated dopamine toxicity. The large COMT aggregates were co-localized with
      the centrosome, suggesting an aggresome-like structure. Our results indicate that
      COMT impairment induced by PGJ2 treatment may increase the concentration of
      dopamine (or its metabolites) to neurotoxic levels. Thus, COMT impairment
      following pro-inflammatory events may be a potential risk factor in
      neurodegeneration.

PMID- 16406651
TI  - Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE
      activities.
AB  - Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss
      in mares. Equine EPF correlates inversely with conception and successful
      gestation. In the modified Kenney endometrial biopsy classification system, EPF
      categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe
      fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens
      were stained with H&E, and picrosirius red (specific for fibrillar collagens
      types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF
      beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in
      EPF categories IIB and III endometria strongly suggested myofibroblastic
      transformation. ACE-binding activity was highest in EPF category IIB; however,
      endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to
      the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II
      initiates the expression of TGF-beta1 resulting in myofibroblastic
      transformation. 11Beta-HSD2 in concert appears to modulate the severity of
      endometrial fibrosis.

PMID- 16406652
TI  - Membrane initiated steroid signaling (MISS): computational, in vitro and in vivo
      evidence for a plasma membrane protein initially involved in genomic steroid
      hormone effects.
AB  - Steroid hormones are indispensable for control of vital processes, development,
      reproduction and modulation of behavior. Lack or complete dysfunction of
      glucocorticoid (GC) signaling, in particular, have lethal consequences. Even a
      minor change in the level of circulating cortisol can be of physiological and
      clinical significance. Analysis of the action mechanisms of GC is therefore of
      major importance, especially since natural and synthetic GC are widely used in
      the therapy of GC-responsive diseases. According to the classical genomic concept
      of steroid hormone action, the effects of GC are mediated by specific nuclear
      receptors (GR). Recent findings provide evidence for the existence of additional,
      plasma membrane (PM) located steroid receptors, which are thought to be
      responsible for rapid, non-genomic responses. We present evidence for a PM
      residing protein, termed "steroid hormone recognition and effector complex"
      (SHREC), which plays a pivotal role in the complex network of PM-related non
      genomic responses leading to GR-mediated genomic effects. This conclusion was
      drawn from studies using different in vitro and in vivo models of a GC-target:
      (1) highly purified fractions of osmotically active PM-vesicles isolated from rat
      and human hepatocytes, (2) a computational model of SHREC generated by the
      "automated receptor modeling" (ARM) method, (3) rat liver cell lines transfected
      with a GC-responsive reporter gene construct and (4) young women orally
      administered with selected steroids. We conclude that SHREC and the GR
      participate in the same signaling chain, SHREC<-->steroid interaction is the
      initial step and an interdependent part of the complete GC signal propagation,
      thus called "membrane initiated steroid signaling" (MISS).

PMID- 16406653
TI  - Vitamin D signaling is modulated on multiple levels in health and disease.
AB  - Vitamin D signaling is dependent on the availability and turnover of the active
      Vitamin D receptor (VDR) ligand 1,25-dihydroxycholecalciferol and on the
      efficiency of VDR transactivation. Activating and inactivating secosteroid
      metabolizing p450 enzymes, e.g. 25-hydroxylases, 1alpha-hydroxylase and 24
      hydroxylase, are responsible for ligand availability on the basis of substrate
      production in the skin and of nutritional intake of precursors. Net availability
      of active hormone depends on the delivery of substrate and the balance of
      activating and inactivating enzymes. 1Alpha-hydroxylase is the critical
      activating enzyme. It is expressed in the kidney for systemic supply and in
      target tissues for local secosteroid activation. It is upregulated in the kidney
      by low calcium intake and parathyroid hormone, downregulated by phosphatonins and
      proinflammatory signal transduction. Transactivation of VDR depends on the
      correct molecule structure, effective nuclear translocation and the presence of
      the unliganded heterodimer partner retinoid X-receptor (RXR) and other nuclear
      cofactors. Rapid Vitamin D-dependent membrane associated effects and consecutive
      second messenger activation exert an own pattern of gene regulation. A membrane
      receptor for these effects is hypothesized but not yet identified. Rickets is the
      long known clinical syndrome of impaired Vitamin D signaling due to Vitamin D3
      deficiency. It can be caused by inherited defects of the cascade, nutritional
      deficits, lack of sunlight exposure, malabsorption and underlying diseases like
      chronic inflammation. It has been shown during the last decades that many
      modifiers of Vitamin D signaling are targets of disease in terms of inherited and
      acquired syndromes and that Vitamin D signaling is modulated at multiple levels
      and is more complex than mere mechanistic ligand/receptor/DNA interaction.

PMID- 16406654
TI  - Hepatic steatosis in the absence of tumor necrosis factor in mice.
AB  - Tumor necrosis factor (TNF) has pleiotropic effects including on hepatic
      metabolism. Here we investigated the effect of high cholesterol diet (1.25%) in
      TNF deficient mice. TNFalpha/beta deficient mice developed hepatomegaly and
      extensive steatosis in the absence of steatohepatitis as compared to wild type
      mice. Saturated and unsaturated, prominently mono- but also poly-unsaturated
      fatty acids (MUFA, PUFA) prevailed in steatotic livers. Down-regulation of the
      cholesterol scavenger receptor B1 and reduced insulin induced phosphorylation of
      protein kinase B in cholesterol fed TNFalpha/beta deficient mice likely
      contributed to the development of hepatic steatosis, which was accompanied by
      increased body weight and bone length. Steatosis was only present in
      TNFalpha/beta double deficient mice, however not in single TNF deficient mice
      suggesting a redundant role of TNFalpha and TNFbeta. In conclusion, high
      cholesterol diet causes an abnormal metabolic phenotype in the simultaneous
      absence of both TNFalpha and beta signals. The presence of either TNFalpha or
      beta alone is sufficient to reconstitute the control of lipid homeostasis.

PMID- 16406655
TI  - Interleukin-21 mRNA expression during virus infections.
AB  - Interleukin-21 is a cytokine with profound impact on the proliferation and
      differentiation of activated leukocytes of both the innate and adaptive immune
      system. In experiments in vitro, antigen activation induces IL-21 production in
      CD4+ T cells. Where, when, and how the proliferative and activational effects of
      IL-21 on different leukocytes come into play in vivo in an immune response has so
      far not been fully investigated. We show here for the first time in vivo, that IL
      21 mRNA is produced in the spleen when mice are challenged with herpes simplex
      virus type 2 (HSV-2) or lymphocytic choriomeningitis virus (LCMV). We show in HSV
      2 challenged mice that this production takes place in CD4+ T cell fractions and
      is absent in CD4+ T cell-depleted fractions. We also show that the peak of IL-21
      mRNA production in both the HSV-2 and LCMV-challenged mice coincides with the
      onset of the adaptive immune response. Thus, our data suggest a role for IL-21 in
      the early stages of adaptive immune response against virus infections.

PMID- 16406656
TI  - Plasma interleukin (IL)-18 (interferon-gamma-inducing factor) and other
      inflammatory cytokines in patients with gouty arthritis and monosodium urate
      monohydrate crystal-induced secretion of IL-18.
AB  - To determine whether levels of interleukin (IL)-18, together with those of IL
      1beta, tumor necrosis factor-alpha, IL-6, and IL-8, are elevated in the plasma of
      patients with gouty arthritis, the plasma concentrations of those cytokines were
      measured in 31 males with gouty arthritis. Further, CD14+ cells were obtained
      from human blood and thioglycolate medium-induced peritoneal cells obtained from
      caspase 1-deficient mice, and then separately cultured in the presence of
      monosodium urate monohydrate (MSU) crystals. In addition, in an animal in vivo
      experiment, MSU crystals were injected into subcutaneous air pouches of IL-18
      deficient mice. The plasma concentrations of IL-18, IL-6, and IL-8 were elevated
      in the presence of gouty arthritis in the gout patients. In the in vitro study,
      the presence of MSU crystals stimulated CD14+ cells (monocytes) to secrete IL-18
      and increased the activity of caspase 1 in CD14+ cells, whereas there was no
      significant effect on IL-18 messenger RNA in CD14+ cells and only a slight
      induction of IL-18 secretion from thioglycolate medium-induced caspase 1
      deficient peritoneal cells. In the in vivo experiment, MSU crystals injected into
      the air pouch promoted neutrophil accumulation along with an increase in
      concentrations of keratinocyte-derived chemokine (KC) and macrophage inflammatory
      protein (MIP)-1alpha in air-pouch fluids in both IL-18-deficient and wild-type
      mice. However, there was no increase in the concentration of IL-18 in air-pouch
      fluids in either mouse strain. Our results suggest that plasma IL-18, IL-6, IL-8,
      and C-reactive protein (CRP) levels reflect local inflammation associated with
      gouty arthritis, though IL-18 does not play an important role in neutrophil
      accumulation. Further, they suggest that MSU crystals accelerate the processing
      of IL-18 from an inactive to active form via the activation of caspase 1.

PMID- 16406657
TI  - [Tocolysis with nifedipine: its use in current practice. Gynecol Obstet Fertil
      2005;33:483-7].

PMID- 16406658
TI  - [Twin delivery: a survey of French obstetrical policies].
AB  - OBJECTIVES: To describe obstetrical policy variations concerning the delivery
      management in the case of twins, at term. PATIENTS AND METHODS: A mail survey was
      undertaken among the medical supervisors of the maternity wards belonging to the
      AUDIPOG Network (N=170). RESULTS: The participating rate was 73.35%. 124 answers
      were analysed. Elective caesarean was realized by 0.8% of participants for
      diamniotic twins and by 57% of cases for monamniotic twins An elective caesarean
      is planned for respectively 74% of answers if first (J1) and second twin (J2) are
      in a breech presentation, 81% if J1 is in breech and J2 in cephalic presentation,
      and 68% if J1 is in breech and J2 in transverse presentation. Delivery with J1 in
      breech and J2 in cephalic presentation had a higher risk than a delivery of a
      single breech at term. When J1 and J2 had a breech presentation 73% of
      participants thought that this delivery is more difficult than a delivery of a
      single breech at term. However, they were only 17.5% to consider that a delivery
      of twin with J1 in cephalic and J2 in breech presentation had a higher risk than
      a single breech delivery. DISCUSSION AND CONCLUSION: Medical policy variations
      are not extensive except for X-ray pelvimetry and the presence for the delivery
      of one paediatrician and one anaesthesiologist. An elective caesarean policy for
      twins is infrequent in France.

PMID- 16406659
TI  - [Neonatal morbidity after conservative management followed by systematic delivery
      at thirty-four weeks of gestation in preterm rupture of membranes. Gynecol Obstet
      Fertil 2005;33:577-81].

PMID- 16406660
TI  - [Recommendations for good practice: drug therapy for genital endometriosis
      (except adenomyosis) (November 2005)].

PMID- 16406661
TI  - [Management of ectopic pregnancy in developing countries: example of a Nigerian
      reference maternity].
AB  - OBJECTIVE: We report 143 cases of ectopic pregnancy (EP) treated in the Issaka
      Gazobi maternity of Niamey between January 1st, 1999 and April 30th, 2001 (28
      months). The objective of this study was to estimate the epidemiological,
      diagnostic and therapeutic aspects to propose actions, which could lead to the
      improvement of the prognosis of EP. PATIENTS AND METHODS: The frequency of
      ectopic pregnancy was 2.32% in our study. The patients were young and pregnant
      for the second or third time. Frequently we observed previous sexually contagious
      infections and/or abortions. More than 70% of the patients were admitted for a
      complicated stage of EP. RESULTS: The culdocentesis allowed to evoke the
      diagnosis in more than 80% of the cases. It is a simple gesture, which makes it
      possible to make the diagnosis of EP and which should be taught and practised in
      maternities of the developing countries. The pelvic ultrasonography and the
      laparoscopy allowed the diagnosis in the other cases. The tubal localization was
      the most frequent, cervical and abdominal pregnancies were found. The surgical
      treatment conducted by laparotomy was conservative in 11.9% and radical in 87.4%
      of the cases. The mortality rate was still 0.70%. DISCUSSION AND CONCLUSION:
      Prevention of the sexually contagious infections and medical management of
      abortions are important to reduce the risks of ectopic pregnancies. Education of
      the patients, living far from the maternity, is also necessary to obtain more
      precocious consultation in case of pregnancy in order to improve the prognosis of
      EP.

PMID- 16406662
TI  - [Magnesium sulphate for the management of preeclampsia].
AB  - In case of eclampsia, and especially in case of preeclampsia, no consensus exist
      in order to treat or to prevent convulsions by routine use of magnesium sulphate,
      at least in France. However, a large, multicentre, randomised trial compared the
      efficacy of magnesium sulphate with diazepam or phenytoin in eclamptic women. In
      this trial, magnesium sulphate was associated with a significantly lower rate of
      recurrent seizures and lower rate of maternal death than that observed with other
      anticonvulsants. The primary objective of magnesium sulphate prophylaxis in women
      with preeclampsia is to prevent or reduce the rate of eclampsia and complications
      associated with eclampsia. There are 3 large randomised controlled trials
      comparing the use of magnesium sulphate to prevent convulsions in patients with
      severe preeclampsia: the first one was vs phenytoin, the second vs placebo, and
      the third vs nimodipine. Patients receiving magnesium sulphate presented a
      significant lower risk of eclampsia than that observed with other comparison
      groups, probably by decreasing the cerebral perfusion pressure, thus avoiding a
      cerebral barotrauma. However, several arguments balance a wide use of magnesium
      sulphate: the prevalence of eclampsia in the Western world is very low, the use
      of magnesium sulphate does not affect the neonatal morbidity and mortality, and
      it is associated with a high rate of side effects, sometimes severe, such as
      respiratory depression. Thus, the benefit to risk ratio has to guide the use of
      magnesium sulphate and is directly correlated to the prevalence of eclampsia
      according to the risk of considered group. 1) The rate of seizures in women with
      mild preeclampsia not receiving magnesium sulphate is very low. Magnesium
      sulphate may potentially be associated with a higher number of adverse maternal
      effects. Therefore, the benefit to risk ratio does not support routine use of
      magnesium sulphate prophylaxis in this group. 2) On the other hand, the higher
      rate of seizures in women with severe preeclampsia (2.0%), especially in those
      who have imminent eclampsia, justifies prophylaxis with magnesium sulphate.

PMID- 16406663
TI  - [For the reasonable use of clomiphene citrate for unexplained infertilities].

PMID- 16406664
TI  - [Against the use of clomiphene citrate for unexplained infertilities].

PMID- 16406665
TI  - Effect of opioid mu-receptors activation on insulin signals damaged by tumor
      necrosis factor alpha in myoblast C2C12 cells.
AB  - In an attempt to develop a new target for handling of insulin resistance, we
      investigated the effect of opioid mu-receptor activation on insulin signals in
      differentiated myoblast C2C12 cells damaged by tumor necrosis factor-alpha
      (TNFalpha). A marked reduction of insulin-stimulated radioactive 2-deoxyglucose
      (2-DG) uptake was observed in TNFalpha (10 ng/ml for 1 h)-treated cells.
      Loperamide (10 micromol/l for 24 h) reversed the inhibition of insulin-stimulated
      2-DG uptake by TNFalpha in a manner sensitive to blockade of opioid mu-receptors.
      Insulin signals damaged by TNFalpha were the impaired expressions of insulin
      receptor (IR), tyrosine autophosphorylation in IR, and insulin receptor substrate
      (IRS)-1 protein, as well as a decrease of IRS-1 tyrosine phosphorylation. Also,
      the signaling defects including an attenuated p85 regulatory subunit of
      phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation were
      observed. Loperamide (10 micromol/l for 24 h) reversed the TNFalpha-induced
      decrement of insulin signals at same concentration used to raise glucose uptake.
      In conclusion, activation of opioid mu-receptors may reverse the insulin signals
      damaged by inflammatory cytokine.

PMID- 16406666
TI  - Increase in bFGF-responsive neural progenitor population following contusion
      injury of the adult rodent spinal cord.
AB  - The number of neural progenitor cells, especially nestin+ cells or BrdU-uptake
      cells is sparse in the normal adult rodent spinal cord. However, in the present
      study, we show that after spinal cord injury (SCI), many ordinarily quiescent
      cells were activated to become nestin+ and undergo mitosis (BrdU+) in the
      ependymal layer as well as in the parenchyma of the spinal cord. Nestin+ cells
      and BrdU+ cells were in most cases immunohistochemically GFAP+, some of which
      displayed radial glial cell morphology and partly participated in the border
      formation of the lesion. The culturing of injured rat spinal cord tissues
      generated more neurospheres earlier than did the culturing of intact tissues, and
      these neurosphere cells were multipotent and bFGF-responsive. Immunohistochemical
      analysis showed that there existed many bFGF+ cells after SCI, the number of
      which were almost 15 times greater than that in an intact spinal cord. Increased
      bFGF production after SCI might activate quiescent progenitor cells, and thus
      initiate their cell proliferation. Finally, SCI to the nestin-promoter green
      fluorescent protein (GFP) transgenic mice showed broad proliferation of
      progenitor cells that were induced in the injured spinal cord. The culturing of
      injured spinal cord tissues from these transgenic mice provides direct evidence
      that neurospheres can be generated by SCI-activated nestin+ cells. Thus, the
      activation of bFGF-responsive progenitor cells and the concomitant increase in
      the population of bFGF+ cells following SCI might be beneficial for spinal cord
      repair if these progenitor cells are properly manipulated.

PMID- 16406667
TI  - 5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in
      serotonin neurons of the raphe nuclei after immobilization stress in the male
      rat.
AB  - The serotoninergic system and the 5-HT1A receptors have been involved in the
      brain response to acute stress. The aim of our study was evaluate the role of the
      5-HT1A receptors in serotoninergic cells of rostral and caudal raphe nuclei under
      acute immobilization in rats. Double immunocytochemical staining of 5-hydroxy
      tryptamine and c-Fos protein and stereology techniques were used to study the
      specific cell activation in the raphe nuclei neurons in five groups (control
      group, immobilization group (immobilization lasting 1 h), DPAT group (8-OH-DPAT
      0.3 mg/kg, s.c.), DPAT+IMMO group (8-OH-DPAT 0.3 mg/kg, s.c., 30' prior acute
      immobilization) and WAY+DPAT+IMMO group (WAY-100635 0.3 mg/kg, s.c. and 8-OH-DPAT
      0.3 mg/kg, s.c., 45' and 30', respectively, before immobilization). Our results
      showed an increase in the number of c-Fos immunoreactive nuclei in serotoninergic
      cells in both dorsal and median raphe nuclei in the immobilized group. The 8-OH
      DPAT pretreatment counteracted the excitatory effects of the acute immobilization
      in these brain regions. In addition, WAY-100635 administration reduced the effect
      of 8-OH-DPAT injection, suggesting a selective 5-HT1A receptor role. Raphe
      pallidus and raphe obscurus did not show any differences among experimental
      groups. We suggest that somatodendritic 5-HT1A receptors in rostral raphe nuclei
      may play a crucial role in both mediating the consequences of uncontrollable
      stress and the possible beneficial effects of treatment with 5-HT1A receptor
      agonists.

PMID- 16406669
TI  - Thiopental inhibits glycine receptor function in acutely dissociated rat spinal
      dorsal horn neurons.
AB  - Whole-cell patch-clamp was used to assess the modulatory effect of thiopental
      (Thio) on glycine (Gly) receptor in mechanically dissociated rat spinal dorsal
      horn neurons. It was found that Thio inhibited the amplitude, accelerated the
      desensitization and prolonged the deactivation of Gly-induced currents (IGly) in
      a concentration-dependent manner. In addition, a rebound current occurred after
      washout of the co-application of Gly and Thio in most neurons tested. Moreover,
      the inhibitory effect of Thio was not the result of cross-inhibition between Gly
      and GABAA receptors. Furthermore, taurine-induced currents, a low-affinity
      agonist for Gly receptors, were also markedly inhibited by Thio in a similar way
      to IGly. These results indicate that Thio suppresses Gly receptor function and
      suggest that Thio anesthetic actions might not be mediated by Gly receptors. We
      speculate that the weak muscle relaxation and the limited analgesic effects
      observed during Thio anesthesia may attribute to its inhibitory effects on Gly
      receptors.

PMID- 16406668
TI  - mu- but not delta- and kappa-opioid receptor mediates the nucleus submedius
      interferon-alpha-evoked antinociception in the rat.
AB  - Previous studies have indicated that interferon-alpha (IFN-alpha) can bind to
      opioid receptors and exerts an antinociceptive effect in both peripheral and
      central nervous systems. The current study investigated the antinociceptive
      effect of IFN-alpha unilaterally microinjected into the thalamic nucleus
      submedius (Sm) of rats on noxious thermal stimulus, and the roles of different
      subtypes of opioid receptors in mediating the Sm IFN-alpha-evoked
      antinociception. The results indicated that unilateral microinjection of IFN
      alpha (4, 8, 16 pmol) into the Sm dose-dependently increased the hind paw
      withdrawal latency from the noxious heat stimulus, and this effect was reversed
      by pretreatment with non-selective opioid receptor antagonist naloxone (200 pmol)
      and specific mu-opioid receptor antagonist beta-FNA (1 nmol) into the same sites,
      whereas delta-opioid receptor antagonist ICI174,864 (1 nmol) and kappa-opioid
      receptor antagonist nor-BNI (1 nmol) failed to alter the effect of IFN-alpha.
      These results suggest that Sm is involved in IFN-alpha-evoked antinociception and
      mu- but not delta- and kappa-opioid receptor mediates the Sm IFN-alpha-evoked
      antinociception.

PMID- 16406670
TI  - Short-term synaptic plasticity in the rat geniculo-cortical pathway during
      development in vivo.
AB  - The critical period for visual system development in rats normally peaks at
      postnatal three weeks and ends at postnatal five weeks. However, the change of
      short-term synaptic plasticity during this period has rarely been investigated.
      In the present study, we compared the short-term plasticity of visual cortical
      responses to lateral geniculate nucleus stimulation in rats at different
      development stages (P20, P30 and adult) in vivo. The results show that paired
      pulse depression (PPD) and frequency-dependent depression of evoked field
      potentials (FP) are present in P20 rats and increase in magnitude with
      development. The time course of this maturation of synaptic depression parallels
      that of the visual critical period. The weak synaptic depression observed in
      juvenile rats may be important in enhancing excitatory neurotransmission at a
      time when synapses are immature; this could endow immature synapses with wide
      integrative capabilities. In contrast, suppressive temporal interactions could
      provide an important substrate for neuronal processing of visual information in
      the mature cortex.

PMID- 16406671
TI  - Association between the brain-derived neurotrophic factor (BDNF) gene and
      schizophrenia in the Chinese population.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to a family of the neurotrophin
      which plays important roles in the development of the brain. BDNF has been
      suggested as a factor that increases the risk of schizophrenia. In this study, we
      genotyped three single nucleotide polymorphisms (SNPs) in the BDNF gene using a
      set sample of Han Chinese subjects consisting of 560 schizophrenes and 576
      controls. No significant differences were found for either the genotype or allele
      distribution of analyzed polymorphisms, nor was any gender-specific association
      found. Thus, our data suggest that the BDNF gene may not be an important factor
      in susceptibility to schizophrenia.

PMID- 16406672
TI  - Pharmacoeconomic consequences of amlodipine besylate therapy in patients
      undergoing PTCA.
AB  - In Italy, revascularization interventions increased from 44,600 in 1996 to more
      than 100,000 in 2001. In particular, the occurrence of percutaneous transluminal
      coronary angioplasty (PTCA) increased from 239 cases per million population in
      1994 to about 1300 cases per million population in 2001. This trend has caused a
      concomitant increase in revascularization costs, which have doubled in few years,
      rising from Euro 421 millions in 1996 to Euro 850 millions in 2001. In 2001, PTCA
      amounted to 55% of total cost of revascularizations. The aim of this study was to
      assess the pharmacoeconomic consequences of amlodipine besylate therapy
      administered in patients at high risk of restenosis after PTCA. We conducted a
      cost-effectiveness analysis comparing therapy with amlodipine besylate added to
      standard care versus standard care alone. Information on clinical outcomes was
      drawn from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES).
      Medical costs were estimated with reference to drug therapy and hospitalizations
      for coronary events and revascularization procedures. The study was conducted
      from the perspective of the Italian third party payer (National Health Service).
      The analysis was applied to a time horizon of 4 months. Amlodipine besylate
      resulted less expensive and more effective than standard care. It reduced
      mortality, morbidity for coronary reasons and the need of revascularization
      procedures. The cost per 1000 patients was estimated at Euro 1,166,000 in the
      placebo and Euro 950,000 in the amlodipine besylate group, resulting into a cost
      saving of Euro 216,000, that is 18.5% of total cost of standard care. Results are
      sensitive to the cost of amlodipine besylate and the cost of hospitalizations,
      but therapy with amlodipine besylate resulted dominant even in the most
      unfavorable hypothesis.

PMID- 16406673
TI  - Adaptive fuzzy k-NN classifier for EMG signal decomposition.
AB  - An adaptive fuzzy k-nearest neighbour classifier (AFNNC) for EMG signal
      decomposition is presented and evaluated. The developed classifier uses an
      adaptive assertion-based classification approach for setting a minimum
      classification threshold. The similarity criterion used for grouping motor unit
      potentials (MUPs) is based on a combination of MUP shapes and two modes of use of
      motor unit firing pattern information: passive and active. The performance of the
      developed classifier was evaluated using synthetic signals with specific
      properties and experimental signals and compared with the performance of an
      adaptive template matching classifier, the adaptive certainty classifier (ACC).
      Across the sets of simulated and experimental EMG signals used for comparison,
      the AFNNC had better average classification performance overall, but due to the
      assignment of higher numbers of MUPs it made relatively more errors. Nonetheless,
      these increased error rates would still be acceptable for most clinical uses of
      decomposed EMG data. An independent and a related set of simulated signals were
      used for testing. For the independent simulated signals of varying intensity, the
      AFNNC had on average an improved correct classification rate (CCr) (8.1%) but an
      increased error rate (Er) (1.5%) compared to ACC. For the related simulated
      signals with varying amounts of shape and/or firing pattern variability, the
      AFNNC on average had an improved CCr (5%) but a slightly increased Er (0.3%)
      compared to ACC. For experimental signals, the AFNNC on average had improved CCr
      (6%) but an increased Er (2.1%) compared to ACC. The greatest gains in AFNNC
      performance relative to that of the ACC occurred when the variability of MUP
      shapes within motor unit potential trains was high suggesting that compared to a
      template matching assignment strategy the NN assignment paradigm is better able
      to ameliorate the classification problems caused by MUP instability.

PMID- 16406674
TI  - Rate-responsive pacing based on the atrio-ventricular conduction time: comparison
      of different algorithms.
AB  - Rate-responsive pacing based on the atrio-ventricular conduction time is a
      promising therapy for restoring physiological heart rate control in chronotropic
      incompetent patients. This paper compares four different algorithms. Three of
      them had been formulated as patents, but no real test or application has been
      reported up to now. The fourth was recently published by the authors of this
      paper. There the steps involved in the development process were stationary and
      dynamic system identification, control system design and a pilot study with
      patients. The data obtained were used to formulate a simulation model of the
      cardiac system by means of which the other algorithms were tested. Test criteria
      were stability, the attenuation of disturbances and the response time to changes
      of the exercise rate. None of the three patents worked when being strictly
      implemented as described. The problems encountered were instability, unusable
      parameterisations and some questionable adaptation mechanisms. In a redesign we
      tried to improve the patents, but only in one case would the results obtained
      justify real use. In the other cases the variability of the pacing frequency was
      intolerably high.

PMID- 16406675
TI  - Automatic correction of artifact from single-trial event-related potentials by
      blind source separation using second order statistics only.
AB  - Event-related potentials (ERP) are in general masked by various kinds of
      artifacts. To attenuate the effects of artifacts, various schemes have been
      introduced, such as epoch rejection, electro-oculogram (EOG) regression and
      independent component analysis (ICA). However, none of the existing techniques
      can automatically remove various kinds of artifacts from a single ERP epoch. EOG
      regression cannot handle artifacts other than ocular ones. ICA incorporating
      higher order statistics (HOS) normally requires data with large number of time
      samples in order that the solution is robust. In this paper we blindly separate
      the multi-channel ERP into source components by estimating the correlation
      matrices of the data. Since only second order statistics (SOS) is involved, the
      process performs well at the single epoch level. Automatic artifact
      identification is performed in the source domain by introducing objective
      criteria for various artifacts. Criteria are based on time domain signal
      amplitude for blink and spurious peak artifact, scalp distribution of signal
      power for eye movement artifact and power distribution of frequency components
      for muscle artifact. The correction procedure can be completed by removing the
      identified artifactual sources from the raw multi-channel ERP.

PMID- 16406676
TI  - Regulation of tumor angiogenesis by thrombospondin-1.
AB  - Angiogenesis plays a critical role in the growth and metastasis of tumors.
      Thrombospondin-1 (TSP-1) is a potent angiogenesis inhibitor, and down-regulation
      of TSP-1 has been suggested to alter tumor growth by modulating angiogenesis in a
      variety of tumor types. Expression of TSP-1 is up-regulated by the tumor
      suppressor gene, p53, and down-regulated by oncogenes such as Myc and Ras. TSP-1
      inhibits angiogenesis by inhibiting endothelial cell migration and proliferation
      and by inducing apoptosis. In addition, activation of transforming growth factor
      beta (TGF-beta) by TSP-1 plays a crucial role in the regulation of tumor
      progression. An understanding of the molecular basis of TSP-1-mediated inhibition
      of angiogenesis and tumor progression will aid in the development of novel
      therapeutics for the treatment of cancer.

PMID- 16406677
TI  - Expression, purification, and refolding of the myeloid inhibitory receptor
      leukocyte immunoglobulin-like receptor-5 for structural and ligand identification
      studies.
AB  - The leukocyte immunoglobulin-like receptors (LIRs, also known as ILTs, CD85, and
      LILRs) comprise a family of related immunoregulatory receptors encoded within the
      leukocyte receptor cluster (LRC) on human chromosome 19. LIRs are transmembrane
      proteins containing either two or four extracellular immunoglobulin domains, and
      most family members are expressed predominantly on myeloid cell lineages.
      Although the inhibitory receptors LIR-1 and LIR-2 are known to bind to a broad
      range of class I MHC molecules and are thought to play important roles in immune
      regulation, the majority of LIRs are currently of unknown structure and their
      ligands remain unidentified. In this study, we describe recombinant production
      and characterisation of the extracellular portion of LIR-5 (ILT3), a poorly
      understood inhibitory receptor that transduces tolerising signals to dendritic
      cells. The two extracellular immunoglobulin domains of LIR-5 were expressed in
      Escherichia coli to a high level and were found to accumulate in inclusion
      bodies. Inclusion bodies were purified, solubilised, and receptor then renatured
      by dilution refolding, with acceptable yields. Size exclusion chromatography and
      SDS-PAGE analyses confirmed the extracellular portion behaved as a monomer in
      solution, and purified protein was antibody-reactive. LIR-5 is representative of
      a subset of LIR receptors that on the basis of structural and sequence
      comparisons with LIR-1 seem unlikely to bind class I MHC molecules. Successful
      prokaryotic generation of correctly folded LIR-5 in high levels has implications
      for production of other LRC receptors and should greatly facilitate attempts to
      define the structure and ligands of this important regulator of dendritic cell
      function.

PMID- 16406678
TI  - Expression of compstatin in Escherichia coli: incorporation of unnatural amino
      acids enhances its activity.
AB  - Compstatin, a 13-residue cyclic peptide, is a complement inhibitor that shows
      therapeutic potential. Several previous approaches have improved the activity of
      this peptide several-fold. In the present study, we have expressed and purified
      compstatin from Escherichia coli in an effort to increase its potency and to
      generate it in high yield in a more economical fashion. An intein-based
      expression system was used to express compstatin in fusion with chitin-binding
      domain and Ssp DnaB intein, which were later cleaved from the expressed molecule
      at room temperature and pH 7.0 to yield pure compstatin in one step. The
      expressed compstatin showed activity similar to the synthetic compstatin in an
      ELISA-based assay. The same expression system and purification strategy were used
      to incorporate three tryptophan analogs, 6-fluoro-tryptophan, 5-hydroxy
      tryptophan, and 7-aza-tryptophan, into compstatin. Interestingly, incorporation
      of 6-fluoro-tryptophan increased the activity three-fold relative to wild-type
      compstatin; in contrast, incorporation of 5-hydroxy- or 7-aza-tryptophan rendered
      compstatin less active than the wild-type form.

PMID- 16406679
TI  - A biological approach to computational models of proteomic networks.
AB  - Computational modeling is useful as a means to assemble and test what we know
      about proteins and networks. Models can help address key questions about the
      measurement, definition and function of proteomic networks. Here, we place these
      biological questions at the forefront in reviewing the computational strategies
      that are available to analyze proteomic networks. Recent examples illustrate how
      models can extract more information from proteomic data, test possible
      interactions between network proteins and link networks to cellular behavior. No
      single model can achieve all these goals, however, which is why it is critical to
      prioritize biological questions before specifying a particular modeling approach.

PMID- 16406680
TI  - Dopamine profoundly suppresses excitatory transmission in neonatal rat
      hippocampus via phosphatidylinositol-linked D1-like receptor.
AB  - Dopamine modulates synaptic transmission in various brain regions. The disorder
      of dopamine system may be related to neurodevelopmental dysfunction. However, the
      action of dopamine on synaptic transmission during development is largely
      unknown. We studied the effect of dopamine on GABAergic and glutamatergic
      transmission in neonatal rat hippocampus from the early period of synapse
      formation by whole-cell patch-clamp recordings from CA1 pyramidal cells. Dopamine
      (100 muM) profoundly decreased the amplitude of GABA(A) receptor-mediated
      postsynaptic currents (GABA(A)-PSCs) to 32.2+/-5.4% (mean+/-S.E.M., EC(50): 2.9
      muM) in the first postnatal week, when GABA provides excitatory drive. Dopamine
      also decreased the amplitude of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents
      (EPSCs) to 29.1+/-2.7% (EC(50): 18.7 muM) in the second postnatal week, when
      glutamate responses first appear. The dopamine-induced inhibition declined after
      these periods and became only partial after postnatal day 30. Further we
      identified the receptor subtype involved in the dopamine-induced inhibition as
      phosphatidylinositol-linked D1-like receptor, since 6-chloro-2,3,4,5-tetrahydro-3
      methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol hydrobromide (SKF 83959), a
      selective agonist for phosphatidylinositol-linked D1-like receptor, clearly
      mimicked the action of dopamine, and 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]
      trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), an inhibitor of
      phospholipase C, significantly reduced the dopamine-induced inhibition. Dopamine
      did not change the response to puff-applied GABA or kainic acid, nor the
      amplitude of miniature GABA(A)-PSCs or miniature EPSCs. These results suggest
      that the activation of phosphatidylinositol-linked D1-like receptor profoundly
      suppresses the excitatory transmission during the early period of synapse
      formation in the developing hippocampus by presynaptic mechanisms. This study
      firstly demonstrates the effect of phosphatidylinositol-linked D1-like receptor
      on synaptic transmission.

PMID- 16406681
TI  - The distribution of chitin in larval shells of the bivalve mollusk Mytilus
      galloprovincialis.
AB  - The insoluble matrix of larval shells of the marine bivalve mollusk Mytilus
      galloprovincialis is investigated by confocal laser scanning microscopy using a
      GFP fusion protein with a chitin-binding domain for labeling of chitinous
      structures. We show that chitinous material is present in the larval shell,
      presumably as a chitin-protein complex. We further show that the structure of the
      chitinous material changes with the development of the larvae. We conclude from
      the presence of characteristic chitinous structures in certain shell regions that
      chitin fulfills an important function in the formation and functionality of
      larval bivalve shells.

PMID- 16406683
TI  - A case of intramuscular cysticercosis diagnosed definitively by mitochondrial DNA
      analysis of extremely calcified cysts.
AB  - A case of obsolete intramuscular cysticercosis diagnosed definitively by
      mitochondrial DNA analysis of extremely calcified cysts was reported. X-ray and
      computed tomography findings highly suggested cysticercosis due to Taenia solium;
      however, no direct evidence of cysticercosis was obtained through serological or
      histopathological examinations. Mitochondrial DNA analysis of a histopathological
      specimen confirmed the causative agent to be the Asian genotype of T. solium.

PMID- 16406684
TI  - Epidemiology and control of echinococcosis in sub-Saharan Africa.
AB  - Cystic echinococcosis (CE) is highly endemic among the nomadic pastoral tribes of
      East Africa, but is rare amongst the agriculturally based communities.
      Echinococcus granulosus infections are common in dogs from all countries in sub
      Saharan Africa where they have been examined. Transmission of E. granulosus to
      humans is affected by such factors as prevalence of the parasite in domestic
      dogs, behaviors of humans towards dogs, and heterogenicity of the parasite and
      susceptibility of humans to infection. Sheep and goats appear to be the most
      common domestic intermediate hosts, but recent studies suggest that camels are
      equally important intermediate host, especially in Sudan and Turkana. At least
      five of ten E. granulosus genotypes are infective to humans in sub-Saharan
      African. Most human cases of CE are caused by the sheep strain (GI) and camel
      strain (G6) of E. granulosus. Other strains occurring in the area may include a
      lion strain, the horse strain (G4 or Echinococcus equinus) and the cattle strain
      (G5 or Echinococcus ortleppi).

PMID- 16406682
TI  - The asymmetry in the mature amino-terminus of ClpP facilitates a local symmetry
      match in ClpAP and ClpXP complexes.
AB  - ClpP is a self-compartmentalized proteolytic assembly comprised of two, stacked,
      heptameric rings that, when associated with its cognate hexameric ATPase (ClpA or
      ClpX), form the ClpAP and ClpXP ATP-dependent protease, respectively. The
      symmetry mismatch is an absolute feature of this large energy-dependent protease
      and also of the proteasome, which shares a similar barrel-shaped architecture,
      but how it is accommodated within the complex has yet to be understood, despite
      recent structural investigations, due in part to the conformational lability of
      the N-termini. We present the structures of Escherichia coli ClpP to 1.9A and an
      inactive variant that provide some clues for how this might be achieved. In the
      wild type protein, the highly conserved N-terminal 20 residues can be grouped
      into two major structural classes. In the first, a loop formed by residues 10-15
      protrudes out of the central access channel extending approximately 12-15A from
      the surface of the oligomer resulting in the closing of the access channel
      observed in one ring. Similar loops are implied to be exclusively observed in
      human ClpP and a variant of ClpP from Streptococcus pneumoniae. In the other
      ring, a second class of loop is visible in the structure of wt ClpP from E. coli
      that forms closer to residue 16 and faces toward the interior of the molecule
      creating an open conformation of the access channel. In both classes, residues 18
      20 provide a conserved interaction surface. In the inactive variant, a third
      class of N-terminal conformation is observed, which arises from a conformational
      change in the position of F17. We have performed a detailed functional analysis
      on each of the first 20 amino acid residues of ClpP. Residues that extend beyond
      the plane of the molecule (10-15) have a lesser effect on ATPase interaction than
      those lining the pore (1-7 and 16-20). Based upon our structure-function
      analysis, we present a model to explain the widely disparate effects of
      individual residues on ClpP-ATPase complex formation and also a possible
      functional reason for this mismatch.

PMID- 16406685
TI  - Keys to success for a school-based malaria control program in primary schools in
      Thailand.
AB  - School-based malaria control has been recognized as a new approach for the
      control of this disease in the Greater Mekong Subregion since 2000. We evaluated
      a school-based malaria control program near the western border of Thailand using
      a before-after intervention study. The major intervention activities included
      teacher training with specialized malaria teaching materials and participatory
      learning methods. The target population was 17 school principals, 111 teachers
      and 852 schoolchildren of grade 3, 4, and 5 in 17 schools. After the
      intervention, the teachers taught about malaria more actively than before. The
      teachers who could design a lesson plan on malaria increased from 30.7% to 47.7%
      (p=0.015) and the teachers who had taught about malaria increased from 71.9% to
      84.3% (p=0.035). As a result of the program, the schoolchildren changed their
      behavior positively towards malaria prevention with significant difference in 6
      of 7 questions. For example, the schoolchildren 'who always took care of mosquito
      bites' increased from 42.7% to 62.1% (p<0.001) and the schoolchildren 'who always
      reported their parents or teachers when they had fever' increased from 36.0% to
      56.0% (p<0.001). In conclusion, the keys to a successful intervention lie in good
      teaching materials and a participatory approach utilizing the well-established
      Thailand's school health system. Beyond Thailand, school-based malaria control
      could be applied to other Greater Mekong Subregion countries with careful
      analysis of school health context in each country.

PMID- 16406686
TI  - Controlled release of DNA vaccines: does in vitro release profile correlate with
      immune response?

PMID- 16406687
TI  - Nicotinic cholinergic antagonists: a novel approach for the treatment of autism.
AB  - Evidence supports the hypothesis that normalization of cholinergic tone by
      selective antagonism of neuronal nicotinic acetylcholine receptors (NNRs) may
      ameliorate the core symptoms of autism. As often is the case, epidemiology has
      provided the first important clues. It is well recognized that psychiatric
      patients are significantly more often smokers than the general population. The
      only known exceptions are obsessive-compulsive disorder (OCD), catatonic
      schizophrenia and interestingly, autism. In this regard, clinical studies with
      nicotine have demonstrated amelioration of symptoms of a number of diseases and
      disorders, including Alzheimer's disease, Parkinson's disease, ADHD and
      Tourette's syndrome. Nicotine's agonist properties at CNS NNRs have been
      implicated in these effects and support the concept of self-medication as a
      strong motivation for smoking in cognitively compromised individuals. On the
      other hand, the inverse correlation between autism and smoking suggests that
      smoking does not provide symptomatic relief and may actually be indicative of an
      active avoidance of nicotine's agonist effects in this disorder. Neuroanatomical
      evidence is consistent with this idea based on the presence of hypercholinergic
      architecture in the autistic brain, particularly during the first few years of
      development, making the avoidance of further stimulation of an already
      hyperactive cholinergic system plausible. This may also explain why stimulants
      (known to increase dopamine levels as do NNR agonists) appear to aggravate
      autistic symptoms and why studies with cholinesterase inhibitors that increase
      acetylcholine levels in the brain have yielded variable effects in autism. Taken
      together, the evidence suggests the possibility that nicotinic cholinergic
      antagonism may in fact be palliative. Pharmacological evidence supports this
      hypothesis. For example, antidepressants, many of which are now known to be non
      competitive NNR antagonists, have been used successfully to treat a number of
      autistic symptoms. More specifically, there is anecdotal evidence from at least
      one medical practitioner that mecamylamine, a non-selective NNR antagonist, is
      effective in treating many autistic symptoms, particularly those that are
      refractory to most other treatments. Clearly there is a need for carefully
      controlled clinical studies with novel selective NNR antagonists to explore their
      potential as a new and exciting approach for the treatment of autism.

PMID- 16406688
TI  - Carnosine may reduce lung injury caused by radiation therapy.
AB  - Ionising radiation is known one of the most effective tools in the therapy of
      cancer but in many thoracic cancers, the total prescribed dose of radiation that
      can be safely administered to the target volume is limited by the risk of
      complications arising in the normal lung tissue. One of the major reasons for
      cellular injury after radiation is the formation of reactive oxygen species
      (ROS). Radiation pneumonitis is an acute phase side-effect which generally
      subsides after a few weeks and is followed by a chronic phase characterized by
      inflammation and fibrosis, that can develop months or years after irradiation.
      Carnosine is a dipeptide composed by the amino acids beta-histidine and l
      alanine. The exact biological role of carnosine is not totally understood, but
      several studies have demonstrated that it possesses strong and specific
      antioxidant properties, protects against radiation damage,and promotes wound
      healing. The antioxidant mechanism of carnosine is attributed to its chelating
      effect against metal ions, superoxide dismutase (SOD)-like activity, ROS and free
      radicals scavenging ability . Either its antioxidant or anti-inflammatuar
      properties, we propose that carnosine ameliorates irradiation-induced lung
      injury. Thus, supplementing cancer patients to whom applied radiation therapy
      with carnosine, may provide an alleviation of the symptoms due to radiation
      induced lung injury. This issue warrants further studies.

PMID- 16406689
TI  - Strong humming for one hour daily to terminate chronic rhinosinusitis in four
      days: a case report and hypothesis for action by stimulation of endogenous nasal
      nitric oxide production.
AB  - Rhinosinusitis is an inflammation or infection of the nose and air pockets
      (sinuses) above, below and between the eyes which connect with the back of the
      nose through tiny openings (ostia). Rhinosinusitis can be caused by bacteria,
      viruses, fungi (molds) and possibly by allergies. Chronic rhinosinusitis (CRS) is
      an immune disorder caused by fungi. The immune response produced by eosinophils
      causes the fungi to be attacked, which leads to damage of the sinus membranes,
      resulting in full-blown rhinosinusitis symptoms. Gaseous nitric oxide (NO) is
      naturally released in the human respiratory tract. The major part of NO found in
      exhaled air originates in the nasal airways, although significant production of
      NO also takes place in the paranasal sinuses. Proper ventilation is essential for
      maintenance of sinus integrity, and blockage of the ostium is a central event in
      pathogenesis of sinusitis. Concentrations of NO in the healthy sinuses are high.
      Nasal NO is known to be increased 15- to 20-fold by humming compared with quiet
      exhalation. NO is known to be broadly antifungal, antiviral and antibacterial.
      This case report shows that a subject hummed strongly at a low pitch (
      approximately 130 Hz) for 1h (18 hums per minute) at bedtime the first night, and
      hummed 60-120 times 4 times a day for the following 4 days as treatment for
      severe CRS. The humming technique was described as being one that maximally
      increased intranasal vibrations, but less than that required to produce
      dizziness. The morning after the first 1-h humming session, the subject awoke
      with a clear nose and found himself breathing easily through his nose for the
      first time in over 1 month. During the following 4 days, CRS symptoms slightly
      reoccurred, but with much less intensity each day. By humming 60-120 times four
      times per day (with a session at bedtime), CRS symptoms were essentially
      eliminated in 4 days. Coincidentally, the subject's cardiac arrhythmias (PACs)
      were greatly lessened. It is hypothesized that strong, prolonged humming
      increased endogenous nasal NO production, thus eliminating CRS by antifungal
      means.

PMID- 16406690
TI  - The gene I love: can romanticism be hidden in a microsatellite polymorphism?

PMID- 16406691
TI  - Effect of lumbar extensor fatigue on paraspinal muscle reflexes.
AB  - Low back disorders are a frequent medical problem. Altered neuromuscular control
      of the spine has been associated with low back pain, and may contribute to its
      occurrence. The purpose of this study was to investigate the effect of lumbar
      extensor fatigue on reflex delay and amplitude in the paraspinal muscles. Ten
      healthy males (20-22 years of age) were subjected to an anteriorly-directed
      perturbation applied at the inferior margin of the scapulae while standing
      quietly before and after a lumbar extensor fatiguing protocol. The fatiguing
      protocol consisted of multiple sets of back extensions and intermittent isometric
      maximum voluntary contraction on a Roman chair for 14 min until 60% of unfatigued
      lumbar extensor MVC was reached. Reflexes were recorded from the paraspinal
      muscles at the level of L4. Results indicated the mean reflex delay was 60+/-18
      ms and was not affected by fatigue (p=0.278). Reflex amplitude increased 36+/-32%
      with fatigue (p=0.017). The increase in reflex amplitude may reflect an attempt
      to compensate for losses in muscle force capacity with fatigue in order to
      maintain sufficient spinal stability. However, additional studies are necessary
      to investigate the mechanisms of this fatigue-related change in paraspinal
      reflex.

PMID- 16406692
TI  - Association of respiratory picornaviruses with acute bronchiolitis in French
      infants.
AB  - BACKGROUND: Human rhinoviruses and enteroviruses (Picornaviridae) are suspected
      to be major viral etiological causes of bronchiolitis in infants. OBJECTIVES: In
      the present study, we assessed the potential role of the respiratory
      picornaviruses as causative agents of bronchiolitis in French infants. STUDY
      DESIGN: From September 2001 to June 2002, we prospectively selected 192 infants <
      or =36 months of age and hospitalized for acute bronchiolitis. The detection of
      common respiratory viruses (respiratory syncytial virus, influenza virus A and B,
      parainfluenza virus 1, 2, 3 and adenovirus) was performed using classical
      immunofluorescence antigen and cell-culture detection assays on nasopharyngeal
      aspirates whereas the detection of human metapneumovirus (HMPV) was performed by
      a real-time RT-PCR assay. The presence of rhinovirus and/or enterovirus was
      assessed in respiratory samples by a picornavirus RT-PCR detection assay followed
      by a differential Southern blotting procedure. RESULTS: A potential causative
      virus was detected in 72.5% of the 192 study infants. RSV (30%), rhinovirus
      (21%), enterovirus (9%), influenza virus A (6%) and human metapneumovirus (4%)
      were the most frequent causative agents detected. Rhinoviruses or enteroviruses
      were detected as the only evidence of respiratory viral tract infection in 57
      (30%) of 192 infants, whereas rhinovirus or enterovirus occurred in mixed viral
      infection detected in 25 (13%) of 192 study cases (30% versus 13%, p<10(-3)).
      CONCLUSIONS: Our data suggest that respiratory picornaviruses are one of the
      leading etiological causes of bronchiolitis in French infants. These findings
      highlight the need to implement a rapid picornavirus RT-PCR detection assay for
      the clinical diagnosis of respiratory infections in pediatric patients with
      bronchiolitis.

PMID- 16406693
TI  - Antiinflammatory activity of Sambucus ebulus hexane extracts.
AB  - Hexane extracts of aerial parts (flowered browes), leaves and roots of Sambucus
      ebulus were investigated for their antiinflammatory activity in rats. Aerial
      parts and roots extracts produced statistically significant and dose dependent
      inhibition of edema induced by carrageenan at all doses when compared to the
      control groups. On the contrary, hexane extract of leaves did not show any
      activity up to 600 mg/kg i.p. The highest activity was showed in the aerial parts
      and roots that at 600 mg/kg i.p. inhibited inflammation by ca. 80% (78% for
      diclofenac at 100 mg /kg i.p.). No extracts exhibit toxicity when injected up to
      2 g/ kg intraperitoneally in mice.

PMID- 16406694
TI  - Serum ghrelin levels are enhanced in patients with epilepsy.
AB  - PURPOSE: In patients with epilepsy, although many changes in the physiology of
      hormones in the neuroendocrine system can occur (especially in the sex hormones,
      for example), the causes of these changes have not been fully elucidated. There
      are also relations between seizure activity and stages of sleep. Ghrelin is the
      peptide hormone, which has been shown to affect both endocrine function and
      sleep. The purpose of this study was to evaluate serum levels of ghrelin in
      epilepsy patients. METHODS: A total of 35 patients currently receiving
      antiepileptic drug therapy (of these patients, 20 had primary generalized seizure
      and 15 had partial seizure) were studied. The control group consisted of 30
      healthy volunteers matched for age and gender. In all participants, serum levels
      of ghrelin, cholesterol and triglycerides were measured and body mass index (BMI)
      was determined. Patients with endocrine, immune or any other chronic diseases
      were excluded. RESULTS: In the epilepsy patients, the mean serum ghrelin level
      was 158.81+/-55.97 pg/ml, and this was significantly higher than the control
      group's level of 93.43+/-21.33 pg/ml (p<0.001). In terms of serum cholesterol,
      triglycerides and BMI, no significant differences were found between the epilepsy
      patients and the control group (p>0.05). CONCLUSIONS: The origin of higher serum
      ghrelin levels in epilepsy and their relation to seizures are not completely
      known. However, this elevation of serum ghrelin could contribute to the
      lengthening of NREM sleep in epilepsy patients, thereby playing a role in seizure
      occurrence. From another direction, high serum ghrelin levels could cause changes
      and/or dysfunction in hormone secretion and physiology via its effects on growth
      hormone, and thereby play a facilitating role in seizure occurrence.

PMID- 16406695
TI  - Clinical experience with topiramate dosing and serum levels in patients with
      epilepsy.
AB  - OBJECTIVE: To investigate the relevance of serum topiramate (TPM) levels (SL)
      monitoring in the clinical management of epileptic patients. METHODS: Twenty
      seven patients with different epileptic syndromes on TPM therapy were studied.
      TPM was used as add-on in 26 patients, only in one as monotherapy de novo; one
      case changed from TPM as add-on to TPM monotherapy. The mean follow-up time was
      11 months. TPM SL were measured by fluorescence polarization immunoassay.
      RESULTS: We analyzed the TPM SL in 43 samples from 27 patients. Mean TPM dose was
      3.9mg/kg, mean TPM SL 13.43mumol/l. The mean level to dose ratio (LDR) was
      3.63mumol/l/mg/kg. Four patients became seizure-free, all with TPM dosages lower
      than the mean. Eleven patients had at least 50% seizure reduction. The
      comedication with enzyme-inducing AED significantly reduced TPM SL and LDR. On
      the other hand, the influence of valproic acid (VPA) on TPM LDR was not univocal.
      Indeed, patients younger than 15 years showed SL values lower than the adults
      did, although not significant. CONCLUSION: We could not detect a direct
      relationship between high TPM SL and efficacy neither between high TPM SL and
      tolerability. However, the data we collected seem to favour the hypothesis that
      high TPM dosage and SL might be associated to a greater probability to reduce
      seizure severity.

PMID- 16406696
TI  - The development of a city-wide epilepsy register.
AB  - The provision of care for patients with epilepsy in the UK is fragmented and
      inadequate. Lack of support in the community, poor communication across the
      primary-secondary care interface and inaccessibility of specialist services are
      contributory factors. The inclusion of epilepsy as a quality marker in the new
      general practitioner (GP) contract provides an opportunity to improve co
      ordination of services. Prior to the acceptance of the New GP Contract in April
      2004, the first part of this audit aimed to (a) assess the documentation of the
      process of care of patients with epilepsy in the city of Chester; and (b) provide
      GPs with a clinical resource to facilitate review of patients and targeting of
      referrals to secondary care. The case notes of 610 patients were scrutinised to
      identify the proportion (a) receiving regular review, (b) in whom diagnosis was
      uncertain, (c) in documented remission, (d) who were women of child-bearing age,
      (e) who were non-compliant with treatment. A computerised template, including
      specific suggestions, was produced for every patient but responsibility for
      review remained with each GP. Re-audit in 2 years was planned. Two hundred and
      fifty (41%) had been seen by a GP in the previous year. One hundred and sixteen
      (19%) had regular review arrangements. One hundred and thirty-eight (22.6%) had
      shared care of whom 79 had seen their GP in previous year. Three hundred and one
      (49%) had not seen any doctor concerning their epilepsy in the previous year.
      Forty-three percent of adults who should be receiving shared care were not doing
      so. In 67 (11%) cases, there was diagnostic uncertainty. Only 178 (29.2%)
      patients were in documented remission. One hundred and nine (17.8%) patients were
      women of child-bearing age of whom 37 were receiving sodium valproate. In 84
      (14%), there was evidence of non-compliance. Haphazard follow-up arrangements
      preclude review of diagnostic accuracy, estimation of remission rate, assessment
      of adherence to prescribed treatment and awareness of level of patients'
      knowledge especially women of child-bearing age on teratogenic drugs. One cannot
      identify those patients who can be managed solely in the community and those who
      merit reassessment in hospital clinics. Assuming these findings are
      representative, primary and specialist secondary care face an enormous task in
      reorganising services to ensure that all patients receive appropriate care. This
      project describes a method of improving local co-ordination of patient care.

PMID- 16406697
TI  - Evidence for a rapid action of levetiracetam compared to topiramate in refractory
      partial epilepsy.
AB  - The objective of this observational study was to compare the efficacy of
      levetiracetam and topiramate during the first 15 days of add-on treatment in
      adults with refractory partial epilepsy. Two cohorts of patients with > or =3
      simple or complex partial seizures with or without secondary generalisation per
      month over an 8-week baseline period received levetiracetam or topiramate in two
      distinct phases, in addition to standard antiepileptic treatment. During the
      first 15 days of the therapy, levetiracetam was added at the dosage of 250 mg
      b.i.d. or topiramate at 25mg o.i.d. Efficacy parameters included number of
      seizure-free days (SFDs), mean and percent reduction in seizure frequency (in
      general and by type), and number of seizure-free patients in the first 15 days of
      treatment compared to last 15 days of the baseline period. Sixty-one patients
      received levetiracetam and 61 topiramate. The general characteristics of the two
      treatment groups were similar. The total number of SFDs during 15 days before
      treatment was 637 with levetiracetam and 621 with topiramate; in the 15-day
      evaluation period the SFDs increased to 748 (17.4%) and 668 (7.6%), respectively
      (ANOVA, p<0.05). Twenty-six patients (42.6%) taking levetiracetam were seizure
      free compared to 10 (16.4%) receiving topiramate (chi-square, p=0.003). This open
      label non-controlled study suggests an early efficacy of levetiracetam as add-on
      therapy in patients with refractory partial epilepsy: these results appear to
      confirm previous indications of a rapid onset of action and seem to suggest first
      evaluation of the patient at the dose of 500 mg/day before increasing to the
      considered minimum standard dose of 1000 mg/day, as some patients could respond
      to the starting dose.

PMID- 16406699
TI  - Towards an understanding of the transcription factor network of dendritic cell
      development.
AB  - Dendritic cells (DCs) are antigen-presenting cells of the immune system and
      develop from hematopoietic stem cells through successive steps of lineage
      commitment and differentiation. The three major DC populations are epidermal
      Langerhans cells, tissue/interstitial/dermal DCs and plasmacytoid DCs. We review
      how gene-targeted mutations in mice have contributed to our understanding of how
      the various DC subpopulations develop. These studies have revealed both
      overlapping and distinct pathways of DC differentiation and show that there is no
      obvious correlation between transcription factor knockout phenotypes and a
      lymphoid or myeloid origin of DCs.

PMID- 16406698
TI  - The immunoregulatory role of IDO-producing human dendritic cells revisited.
AB  - Following the finding that indoleamine 2,3-dioxygenase (IDO), an enzyme expressed
      in the placenta, prevents rejection of allogeneic fetuses in mice, many studies
      have focused on the role of IDO in the regulation of the immune response. Most
      arguments for an immunoregulatory role of IDO in vivo are based on observations
      in mice. Here, we critically examine the arguments for and against a function of
      IDO-expressing human dendritic cells (DCs) and conclude that proof for an
      immunoregulatory role in vivo is still lacking.

PMID- 16406700
TI  - Holding T cells in check--a new role for complement regulators?
AB  - Complement is not only part of the innate immune system, but has also been
      implicated in adaptive immunity. The role of complement and its regulatory
      proteins in modulating T cell activity has been the focus of several recent
      studies. These, which have included work on the membrane co-factor protein (MCP
      or CD46), decay accelerating factor (DAF or CD55) and CD59, indicate that
      complement regulators can influence the proliferative capacity of T cells and
      their ability to produce cytokines, influencing the outcome of a T cell response
      to a given antigen. Here we review these studies, which reveal another important
      link between the innate and the adaptive immune system.

PMID- 16406701
TI  - Long-acting interferon-alpha 2a modified with a trimer-structured polyethylene
      glycol: preparation, in vitro bioactivity, in vivo stability and
      pharmacokinetics.
AB  - The proper selection of size and shape for polyethylene glycol (PEG) is one of
      the most important points in PEGylation technology. Therefore, PEGs of various
      sizes and shapes have been widely developed to endow specific properties. In this
      study, a unique, trimer-structured, 43 kDa PEG was conjugated to interferon-alpha
      2a (IFN) by forming an amide bond to improve the pharmacokinetic properties and
      minimize the loss of IFN bioactivity. Mono-PEGylated IFN (PEG(3)-IFN) prepared by
      utilizing this unique PEG was purified and characterized by cation-exchange
      chromatography and MALDI-TOF mass spectrometry. The in vitro bioactivity, in vivo
      stability, and pharmacokinetics of PEG(3)-IFN were examined and compared to those
      of native IFN. PEG(3)-IFN exhibited comparable in vitro bioactivities to native
      IFN and an excellent stability of the conjugation linkage in rat serum and
      various organs following subcutaneous injection. Furthermore, it showed slow
      absorption and markedly reduced clearance in rats, thereby increasing the
      biological half-life by about 40-fold compared to that of native IFN. This is the
      first report on the application of unique, trimer-structured PEG to bioactive
      proteins. The results suggest that unique, trimer-structured 43 kDa PEG can
      provide some advantages to improve the pharmacokinetic properties and to maintain
      the bioactivity of therapeutic proteins in clinical use.

PMID- 16406702
TI  - Checking and fixing the cellular nanomachinery: towards medical nanoscopy.
AB  - Most diseases, regardless of their diverse etiologies, manifest themselves as
      defects of cellular proteins. Cellular proteins have been recently shown to form
      specific complexes exerting their functions as if they were nanoscopic machines.
      Such nanoscopic protein machines cooperate in functional modules, yielding
      extended, highly compartmentalized networks. The classical resolution limits of
      fluorescence microscopy have also been recently overcome, opening the nanometer
      domain to live-cell imaging. Together, progress in functional proteomics and live
      cell imaging provide novel possibilities for directly analyzing and modifying
      nanoscopic protein machines in living cells and tissues.

PMID- 16406703
TI  - ADAMTS5-mediated aggrecanolysis in murine epiphyseal chondrocyte cultures.
AB  - OBJECTIVE: Aggrecan degradation by aggrecanases [a disintegrin and
      metalloproteinase with thrombospondin-like motifs (ADAMTS) 1, 4, 5, 8, 9, 15] is
      considered to initiate much of the cartilage pathology seen in human arthritis,
      however, the proteinase responsible and its mode of control is unclear. The
      present work was done to examine mechanisms of aggrecanase control in a novel
      murine epiphyseal cell system and to determine whether ADAMTS5 alone is
      responsible for aggrecanolysis by these cells. METHODS: Epiphyseal cells from 4
      day-old mice (wild type, TS-5 (-/-), CD44(-/-), syndecan-1(-/-), membrane type-4
      matrix metalloproteinase [MT4MMP(-/-)]) were maintained in non-adherent aggregate
      cultures and aggrecanolysis studied by biochemical and histochemical methods.
      Confocal immunolocalization analyses were done with specific probes for ADAMTS5,
      hyaluronan (HA) and aggrecanase-generated fragments of aggrecan. RESULTS:
      Aggrecanolysis by these cells was specifically aggrecanase-mediated and it
      occurred spontaneously without the need for addition of catabolic stimulators.
      Chondrocytes from ADAMTS5-null mice were aggrecanase-inactive whereas all other
      mutant cells behaved as wild type in this regard suggesting that ADAMTS5 activity
      is not controlled by CD44, syndecan-1 or MT4MMP in this system.
      Immunohistochemical analysis supported the central role for ADAMTS5 in the
      degradative pathway and indicated that aggrecanolysis occurs primarily in the HA
      poor pericellular region in these cultures. CONCLUSION: These findings are
      consistent with published in vivo studies showing that single-gene ADAMTS5
      ablation confers significant protection on cartilage in murine arthritis. We
      propose that this culture system and the analytical approaches described provide
      a valuable framework to further delineate the expression, activity and control of
      ADAMTS-mediated aggrecanolysis in human arthritis.

PMID- 16406704
TI  - Hypolipemic effect of water extracts of Picrorrhiza rhizoma in PX-407 induced
      hyperlipemic ICR mouse model with hepatoprotective effects: a prevention study.
AB  - The preventive hypolipemic effect of water extract of Picrorrhiza rhizoma (PR)
      was observed in Poloxamer (PX)-407 induced hyperlipemic mice with their
      hepatoprotective effects. Doses of 50, 100 and 200 mg/kg of PR extracts were
      given orally once a day for 12 weeks initiated with intraperitoneal injection of
      PX-407 (0.5 g/kg), and changes in body weight and gains, liver weight, serum
      aspartate transferase (AST) and alanine transferase (ALT) levels were monitored
      with serum low density lipoprotein (LDL), high density lipoprotein (HDL),
      triglyceride and total cholesterol levels. The efficacy of PX-407 was compared to
      that of 10mg/kg of simvastatin (SIMVA). No meaningful changes in the body weight
      were detected in all dosing groups compared to that of vehicle control group.
      Dramatic decrease of both absolute and relative liver weight was dose-dependently
      observed in all PR extracts dosing groups compared to that of vehicle control
      group. The serum AST and ALT levels were significantly and dose-dependently
      decreased in PR extracts dosing groups. However, slight increase of liver weight,
      serum AST and ALT levels were detected in SIMVA-dosing groups. The serum LDL,
      triglyceride and total cholesterol levels were dose-dependently decreased in PR
      extracts dosing groups and SIMVA-dosing group compared to that of vehicle control
      group, respectively. The serum HDL levels were slightly but dose-dependently
      increased in PR extracts dosing groups compared to that in vehicle control group,
      respectively. However, the efficacy on the serum lipid levels of PR extracts was
      lower than that of SIMVA-about 200 mg/kg of PR extracts which showed similar
      effect compared to that of SIMVA 10mg/kg. On the basis of these results, it is
      concluded that water extract of PR has a relatively good favorable preventive
      effect on the PX-407 inducing hyperlipemia with favorable hepatoprotective
      effect.

PMID- 16406705
TI  - The species concept in parasites and other pathogens: a pragmatic approach?
AB  - Although the problem of speciation is a puzzle for evolutionists, species are not
      mere fantasies. In many cases, it is possible to identify evolutionary entities
      that deserve to be attributed the name 'species' and that are relevant to medical
      researchers and decision makers. All approaches to the problem of speciation in
      pathogens are specific cases of four main concepts (or combinations thereof):
      biological, phylogenetic, phenetic and phenotypic. Modern genetic concepts and
      technologies help to juggle these concepts.

PMID- 16406706
TI  - Tolerance is the key to understanding antimalarial drug resistance.
AB  - The evolution of antimalarial drug resistance is often considered to be a single
      stage process in which parasites are either fully resistant or completely
      sensitive to a drug. However, this does not take into account the important
      intermediate stage of drug tolerance. Drug-tolerant parasites are killed by the
      high serum concentrations of drugs that occur during direct treatment of the
      human host. However, these parasites can spread in the human population because
      many drugs persist long after treatment, and the tolerant parasites can infect
      people in which there are residual levels of the drugs. This intermediate stage
      between fully sensitive and fully resistant parasites has far-reaching
      implications for the evolution of drug-resistant malaria.

PMID- 16406707
TI  - Input-specific long-term potentiation in the rat lateral amygdala of horizontal
      slices.
AB  - Long-term potentiation (LTP) at input synapses to the lateral nucleus of the
      amygdala (LA) is a candidate mechanism for memory storage during fear learning.
      Cellular mechanisms of LTP have been nearly exclusively investigated in coronal
      brain slices. In our experiments, we used a horizontal brain slice preparation of
      rats that preserved most of the connections to cortical areas and the
      hippocampus. The stimulation electrodes were located either within the external
      capsule (EC) or the LA. The aim of the present study was to investigate the
      mechanisms of LTP induced either by weak theta burst stimulation (TBS) or strong
      high frequency stimulation (HFS) using the two different stimulation sites.
      Whereas both TBS and HFS of afferences running through the LA induced stable LTP,
      TBS failed to induce LTP of EC-inputs to the LA. The present findings also show
      that LTP in the LA exhibits vulnerability at different time windows after
      induction. The time window was dependent on the kind of stimulated afferences.
      Later LTP becomes resistant to disruption by low frequency stimulation. We could
      show that both used inputs depended on NMDA receptors for LTP-induction. LTP
      induced by stimulation of fibers within the LA was not altered by nifedipine (10
      microM). In contrast, EC-induced LTP was dependent on L-type voltage-gated
      calcium channels (VGCC). Finally, we found a higher magnitude of LTP in females
      using TBS, whereas HFS did not cause gender-specific differences. Our study
      supports the conclusion that the form of LA-LTP depend on which afferences are
      activated and what pattern of stimulation is used to induce LTP.

PMID- 16406708
TI  - Characterization of rhizobia isolated from Albizia spp. in comparison with
      microsymbionts of Acacia spp. and Leucaena leucocephala grown in China.
AB  - This is the first systematic study of rhizobia associated with Albizia trees. The
      analyses of PCR-RFLP and sequencing of 16S rRNA genes, SDS-PAGE of whole-cell
      proteins and clustering of phenotypic characters grouped the 31 rhizobial strains
      isolated from Albizia into eight putative species within the genera
      Bradyrhizobium, Mesorhizobium and Rhizobium. Among these eight rhizobial species,
      five were unique to Albizia and the remaining three were shared with Acacia and
      Leucaena, two legume trees coexisting with Albizia in China. These results
      indicated that Albizia species nodulate with a wide range of rhizobial species
      and had preference of microsymbionts different from Acacia and Leucaena. The
      definition of four novel groups, Mesorhizobium sp., Rhizobium sp. I, Rhizobium
      sp. II and "R. giardinii", indicates that further studies with enlarged rhizobial
      population are necessary to better understand the diversity and to clarify the
      taxonomic relationships of Albizia-associated rhizobia.

PMID- 16406709
TI  - Management of overweight and obesity in adults: behavioral intervention for long
      term weight loss and maintenance.
AB  - BACKGROUND: The World Health Organization has identified obesity as a global
      epidemic. While weight loss is a considerable challenge, long-term maintenance of
      weight loss is an even greater problem. AIMS: This review of the assessment and
      management of overweight and obesity in adults covers factors contributing to
      overweight and obesity, components of weight-loss management, and interventions
      and effects of behavioral treatment for long-term weight loss and maintenance.
      METHODS: A thorough search of the medical and nursing literature recorded in the
      MEDLINE database from 1995 to 2003 was conducted by using the keywords
      "overweight", "obesity", and "behavioral therapy". RESULTS: Obesity is a complex,
      multifaceted condition in which excessive body fat places a person at risk of
      multiple health problems. Excessive body fat results from energy intake that
      exceeds energy expenditure. CONCLUSIONS: Increasing evidence suggests that
      obesity is not simply a problem of will power or self-control but a complex
      disorder involving appetite regulation and energy metabolism that is associated
      with a variety of comorbid conditions. Effective strategies of weight loss
      require management strategies in a combined approach of dietary therapy and
      physical activity by using behavioral interventions.

PMID- 16406710
TI  - Hereditary hyperferritinemia cataract syndrome in three unrelated families of
      western Greek origin caused by the C39 > G mutation of L-ferritin IRE.
AB  - Hereditary hyperferritinemia-cataract syndrome (HHCS) is a well-characterized
      autosomal dominant disease caused by mutations in the iron responsive element
      (IRE) of ferritin L-chain (FTL) mRNA. Mutations in the IRE result in reduced
      binding of the trans-acting iron regulatory proteins (IRPs) and hence in
      upregulation of ferritin L-chain synthesis. The disease is characterized by
      increased L-ferritin in serum and tissues and early onset of bilateral cataracts.
      Iron metabolism is normal, and there is no tissue iron overload. At least 25
      nucleotide substitutions and deletions in the L-ferritin IRE have been described
      in families with HHCS, originating from diverse European, Australian and North
      American populations. We studied the molecular pathogenesis of HHCS in three
      unrelated kinderships of western Greek origin, with 19 affected members. We
      identified a relatively rare C39G mutation located in the hexanucleotide loop of
      L-ferritin IRE. Computational analysis of mRNA folding of mutant FTL IRE
      predicted that the C39 > G mutation leads to a rearrangement of base pairing in
      this critical region, which is likely to modify the IRP binding affinity. All
      subjects with HHCS were heterozygotes for the same C39G mutation. Clinical and
      laboratory phenotypes were described. Moreover, there was evidence of an
      association between this FTL IRE stem-loop mutation and very high ferritin
      levels. Our findings broaden the list of populations where HHCS has been
      described.

PMID- 16406711
TI  - Mild copper deficiency alters gene expression of proteins involved in iron
      metabolism.
AB  - Iron and copper homeostasis share common proteins and are therefore closely
      linked to each other. For example, copper-containing proteins like ceruloplasmin
      and hephaestin oxidize Fe(2+) during cellular export processes for transport in
      the circulation bound to transferrin. Indeed, copper deficiency provokes iron
      metabolism disorders leading to anemia and liver iron accumulation. The aim of
      the present work was to understand the cross-talk between copper status and iron
      metabolism. For this purpose we have established dietary copper deficiency in
      C57BL6 male mice during twelve weeks. Hematological parameters, copper and iron
      status were evaluated. cDNA microarray studies were performed to investigate gene
      expression profiles of proteins involved in iron metabolism in the liver,
      duodenum and spleen. Our results showed that copper deficiency induces microcytic
      and hypochromic anemia as well as liver iron overload. Gene expression profiles,
      however, indicate that hepatic and intestinal mRNA expression neither compensates
      for hepatic iron overload nor the anemia observed in this mouse model. Instead,
      major modifications of gene expression occurred in the spleen. We observed
      increased mRNA levels of the transferrin receptors 1 and 2 and of several
      proteins involved in the heme biosynthesis pathway (ferrochelatase, UroD,
      UroS,...). These results suggest that copper-deficient mice respond to the
      deficiency induced anemia by an adaptation leading to an increase in erythrocyte
      synthesis.

PMID- 16406712
TI  - Determination of terpene trilactones in Ginkgo biloba solid oral dosage forms
      using HPLC with evaporative light scattering detection.
AB  - A reversed phase high performance liquid chromatographic method with evaporative
      light scattering detection (RP-HPLC-ELSD) was developed for the quantitative
      determination of the terpene trilactones, ginkgolide A, B, C and J and the
      sesquiterpene, bilobalide in Ginkgo biloba solid oral dosage forms. Separation
      was achieved using a minibore Phenomenex Luna (5 microm) C18 column with
      dimensions 250 mm x 2.00 mm maintained at a temperature of 45 degrees C. A simple
      gradient method using a mobile phase of methanol:water and a flow rate of 350
      microl/min facilitated baseline separation of the selected marker compounds
      within 14 min. The ELSD parameters affecting the detector response were optimized
      prior to the validation. The limits of detection and quantification were 31.25
      and 62.50 ng, respectively. The percentage relative errors of the recovery ranged
      between -3.16 and +1.88 and both intra-day and inter-day percentage standard
      deviations were all better than 6%. This method was used to assay commercially
      available Ginkgo biloba products and proved to be suitable for the routine
      analysis of such products for quality control purposes.

PMID- 16406713
TI  - Separation and determination of strychnine and brucine in Strychnos nux-vomica L.
      and its preparation by nonaqueous capillary electrophoresis.
AB  - An easy, rapid method for simultaneous determination of strychnine and brucine in
      Strychnos nux-vomica L. and its preparation was developed by nonaqueous capillary
      electrophoresis (NACE) without pretreatment for the first time. Optimum
      separation was achieved with a fused-silica capillary column (50 cmx75 microm
      i.d.) and a running buffer containing 30 mM ammonium acetate, 1.0% acetic acid
      and 15% acetonitrile (ACN) in methanol medium. The applied voltage was 30.0 kV.
      The analytes were detected by UV at 214 nm. The effects of concentration of
      ammonium acetate, acetic acid and organic modifier on electrophoretic behavior of
      the analytes were studied. The established method with sophoridine as internal
      standard was linear in the range of 5-1000 mg/mL for both strychnine and brucine.
      The extracts of Strychnos nux-vomica and its preparation could be directly
      injected for determination with recoveries ranging from 94.5 to 104%.

PMID- 16406714
TI  - Unresponsiveness of C-reactive protein in the non-infectious inflammation of
      systemic lupus erythematosus is associated with interleukin 6.
AB  - C-reactive protein (CRP) response is abnormal to a non-infectious inflammation in
      systemic lupus erythematosus (SLE). We evaluated the role of cytokines in this
      CRP unresponsiveness. The sera of 138 SLE patients and 71 rheumatoid arthritis
      patients were collected prospectively. SLE with infection had higher WBC count,
      ESR, CRP and C4 levels than those without infection. IL-6, IL-10 and IFN-gamma
      levels were higher in SLE with infection than SLE without infection. In SLE with
      infection, the CRP was correlated with the IL-6 (r = 0.77, P < 0.001) but not
      correlated with IL-10 and IFN-gamma. These data suggest that IL-6 may have a role
      in the unresponsiveness of CRP to a non-infectious inflammation of SLE.

PMID- 16406715
TI  - Molecular graphics approach to bacterial AcrB protein-beta-lactam antibiotic
      molecular recognition in drug efflux mechanism.
AB  - AcrAB-TolC is the most important multidrug efflux pump system of Gram-negative
      bacteria, responsible for their resistance to lipophilic and amphiphilic drugs.
      In this work, a molecular graphics study of the pump components AcrB and TolC, 16
      beta-lactam antibiotics and 7 other substrates, as well as of AcrB-substrate
      complexes, was performed in order to give a mechanistic proposal for the efflux
      process at molecular level. AcrAB-TolC is a proton-dependent electromechanical
      device which opens to extrude drugs from the bacterial periplasm and perhaps
      cytoplasm, by means of a series of structural changes within the complex and its
      components AcrA, AcrB and TolC. These changes are initiated by protonation and
      disruption of salt bridges and certain hydrogen bonds, and are followed by
      conformational changes in which a number of intra- and interchain interactions
      are rearranged. Molecular properties of beta-lactams accounting for their
      lipophilicity, shape/conformation and other sterical features, polar/charge group
      distribution and other electronic properties, and hydrogen bonding potency
      determine their interaction with polar headpieces of the inner membrane,
      recognition and binding to receptors of AcrB and TolC. The orientation of the
      beta-lactam molecular dipoles with respect the efflux system is maintained during
      the drug efflux. Elongated cylinder-like beta-lactam antibiotics with lipophylic
      side chains, a significantly negative component of the dipole moment and low
      hydrogen bonding capacity seem to be good substrates of AcrAB-TolC.

PMID- 16406716
TI  - Exploring the potential of complex formation between a mutant DNA and the wild
      type protein counterpart: a MM and MD simulation approach.
AB  - We have demonstrated that the methods of molecular modeling and molecular
      dynamics simulation might be used to assess whether a specific mutation in the
      DNA would destabilize a known DNA-protein complex. The approach is based on
      probing the changes in the interaction that would be induced into the complex if
      within the already formed wild type complex the mutation could be introduced. We
      have used Hoxc8-DNA complex as a test system where it is known that the Hoxc8
      binding affinity of the DNA is completely lost upon mutation of the DNA by
      replacing TAAT stretch to GCCG. Mutation was obtained by changing the relevant
      base pairs into the DNA of the model of the corresponding wild type complex
      developed by homology modeling and MD simulation in water for 2.0 ns. Comparison
      of the structure, dynamics and interactions between the hypothetical mutant model
      with those of the similarly refined wild type model shows that the loss of
      affinity of the mutant DNA to Hoxc8 has two different origins: (i) loss of
      several strong H-bonds as the direct consequences of mutation and (ii) reduced H
      bonds in the common parts due to a net loss or inferior H-bonding geometry
      induced by the mutation as indirect effects. The net change in the interaction
      energy between the DNA and the protein in the best possible configuration
      indicated the experimentally observed destabilization effects. No significant
      change in the groove width was observed and no correlation was found between the
      water-bridges and the loss of affinity.

PMID- 16406717
TI  - Adsorption equilibria of hydrocarbons in the structure of the reforming catalyst:
      molecular modeling.
AB  - Molecular modeling was used to analyze the phenomena involved in the sorption of
      hydrocarbons by the Pt/Al2O3 reforming catalyst. The interactions between the
      atoms of the catalyst structure and the molecules of the model reforming
      compounds were described in terms of the universal forcefield. Making use of the
      GCMC algorithms, the adsorption isotherms for the reagents in the catalytic
      system and the temperature dependence of the Henry constant were determined. The
      research has produced the following major findings: the amount of the hydrocarbon
      molecules adsorbed rises with increasing pressure and decreasing temperature, and
      the adsorption isotherm for toluene has a characteristic plot as compared to the
      isotherms of the other hydrocarbons studied. Mass cloud analysis has revealed a
      favorable effect of platinum on adsorption in the catalyst model.

PMID- 16406718
TI  - Selective pharmacophore design for alpha1-adrenoceptor subtypes.
AB  - Alpha1-adrenoceptors are G-protein coupled receptors found in a variety of
      vascular tissues and responsible for vasoconstriction. Selectivity for each of
      the three subtypes is an important consideration in drug design in order to
      minimise the possibility of side effects. Using Catalyst we developed ligand
      based pharmacophores from alpha(1a,b,d)-selective antagonists available in the
      literature using three separate training sets. Four-feature pharmacophores were
      developed for the alpha(1a) and alpha(1b) subtype-selective antagonists and a
      five-feature pharmacophore was developed for the alpha(1d) subtype-selective
      antagonists. The alpha(1a) pharmacophore represents both class I and II compounds
      with good predictivity for other compounds outside the training set as well. The
      alpha(1b) pharmacophore best predicts the activity of prazosin analogues as these
      make up the majority of alpha(1b)-selective antagonists. Unexpectedly, no
      positive ionisable feature was incorporated in the alpha(1b) pharmacophore. The
      alpha(1d) pharmacophore was based primarily on one structural class of compounds,
      but has good predictivity for a heterogeneous test set. Preliminary docking
      studies using AutoDock and optimised alpha1-adrenoceptor homology models,
      conducted with the antagonists prazosin (32) and 66, showed good agreement with
      the findings from the pharmacophores.

PMID- 16406719
TI  - The chorioallantoic membrane test as a model to predict the potential human eye
      irritation induced by commonly used laboratory solvents.
AB  - The purpose of this study was to investigate the potential eye irritation of a
      range of solvents, extensively used in industry and laboratory and the capacity
      of the chorioallantoic membrane test to predict this eye irritation. The
      irritation has been evaluated by an in vitro method using the chorioallantoic
      membrane as an alternative to in vivo Draize rabbit test. All the solvents
      studied are potentially strongly irritants, even though diluted, except dimethyl
      sulfoxide which was moderately irritant at a concentration of 10% v/v. In some
      cases there is a correlation between the concentration of the solvent and the
      potential eye irritation induced. The method allows prediction of the potential
      eye irritation of the solvents studied.

PMID- 16406720
TI  - Rupture of a left sinus of Valsalva aneurysm into the pulmonary artery.
AB  - Sinus of Valsalva aneurysm is a rare congenital defect and the diagnosis is
      usually made after it ruptures. Very few cases of non-complicated sinus of
      Valsalva aneurysm have been published. The anomaly most often involves the right
      coronary sinus and less frequently the non-coronary sinus. A case with left sinus
      of Valsalva has not been reported. Since the aortic valve occupies a central
      position in the base of the heart, rupture of a sinus of Valsalva aneurysm can
      occur in any of the four heart chambers. Rupture into the pulmonary artery is
      very rare and is mostly associated with other congenital cardiopathies.

PMID- 16406721
TI  - Aerosolised hyaluronic acid prevents exercise-induced bronchoconstriction,
      suggesting novel hypotheses on the correction of matrix defects in asthma.
AB  - Hyaluronic acid (HA), a biopolymer, member of the family of the
      glycosaminoglicanes (GAGs) is one of the major natural components of the
      connective amorphous matrix. The lungs, together with skin and intestine, contain
      >50% of HA of the body: it provides to several biologic functions and presents
      the unique capacity to link and retain a particularly relevant number of water
      molecules. Since other GAGs have been proven to be provided with anti-asthmatic
      properties and HA has been employed with positive results by intra-tracheal
      instillation in experimental models of lung emphysema and COPD, we have explored
      the efficacy of the pre-administered aerosol of HA (compared to placebo) in
      preventing in asthmatic patients the bronchoconstriction induced by a challenge
      test such as that obtained with muscular exercise. In a randomised, cross-over,
      single-blind study design, saline as placebo (P) or HA have been administered by
      aerosol, in two non-consecutive days, 30 min prior to the beginning of the
      challenge (10 min free running), to 14 patients (13-36 years old; 7 teenagers, 7
      young adults; 11 males, 3 females; 12 allergic, 2 non-allergic), all suffering
      from mild bronchial asthma. The bronchoconstrictive effect induced by the
      muscular exercise has been relevant and statistically significant. With the P pre
      treatment, the average FEV1 measured 5 min after the end of exercise was reduced
      by 36.14% from the baseline FEV1. Pre-treatment with HA determined a partial but
      clear-cut protection of the FEV1 impairment due to the challenge: the average
      post-challenge FEV1 resulted to be 12.43% less than the pre-challenge baseline
      value. No significant difference was observed in the level of HA protection in
      the subgroup of teenagers when compared to that of young adults. The protection
      induced by HA, when compared with P, resulted particularly significant by the
      statistical point of view (p < 0.0001). We conclude that aerosol HA
      administration significantly reduces the bronchial hyper-reactivity to muscular
      exercise in asthmatics. Such effect could be attributed to the correction of the
      pathological remodelling, one of the main features of asthma: a correction which
      could be attributed to the unique physicochemical properties of this major
      component of the loose connective amorphous matrix of the airways, which is
      undoubtedly involved in the remodelling process.

PMID- 16406723
TI  - Comparative genomics of the endocrine systems in humans and chimpanzees with
      special reference to GNRH2 and UCN2 and their receptors.
AB  - To identify the genetic basis of the differences between chimpanzees and humans,
      it is indispensable to analyze a whole gene set constituting a particular
      regulatory system as well as to compare the whole genome or chromosomes randomly.
      We compared genes encoding hormones of the endocrine system, one of the most
      fundamental regulatory systems in organisms. The present study covered a total of
      111 genes generating 115 precursors and 172 peptides. Decisive differences were
      observed in GNRH2 and UCN2 and their corresponding receptor genes. It is often
      postulated that mechanisms underlying the basic functions of life are common and
      would not be readily altered. The present study demonstrated that, on the
      contrary, substantial differences have been generated in genes composing the
      endocrine system, even between humans and our closest living relative.

PMID- 16406722
TI  - A novel flow cytometric assay of human whole blood neutrophil and monocyte CD11b
      levels: upregulation by chemokines is related to receptor expression, comparison
      with neutrophil shape change, and effects of a chemokine receptor (CXCR2)
      antagonist.
AB  - RATIONALE: Smokers who develop chronic obstructive pulmonary disease (COPD) have
      amplified inflammation within their lungs, involving selective tissue
      accumulation of neutrophils, macrophages and CD8+ T cells. CD11b (Mac-1,
      alphaMbeta(2)-integrin) is both a complement receptor (CR3) and a cell adhesion
      molecule present on the surface of peripheral blood leukocytes, and undergoes
      rapid surface upregulation from preformed cytoplasmic stores on activation.
      Cellular activation can also trigger chemotaxis and shape change, the activation
      itself being caused by the binding of chemokines to cell surface receptors.
      METHODS: We developed a method of whole blood flow cytometry to measure
      neutrophil and monocyte CD11b upregulation on CD16+ and CD14+ cells, employing
      staining with the nuclear dye LDS-751 immediately before flow cytometry. In
      addition we assessed neutrophil shape change by modified gated autofluorescence
      with forward scatter (GAFS), this being correlated with chemotactic responses.
      RESULTS: In smokers with COPD there was a lower maximal shape change for
      neutrophils in response to CXCL8 (IL-8) in comparison to healthy smokers
      (p=0.025), and a trend for lower expression of CD11b and shape change in response
      to CXCL1 (GRO-alpha). Neutrophils were found to predominantly express chemokine
      receptors CXCR1 and CXCR2 and respond to CXCL8 with CD11b upregulation, while
      monocytes express more CCR2 and upregulate CD11b preferentially to CCL2 (MCP-1).
      A CXCR2 antagonist (SB-656933) was found to inhibit neutrophil CD11b upregulation
      (IC50=260.7nM) and shape change (IC50=310.5nM) in COPD patients. CONCLUSIONS:
      Neutrophils and monocytes participate in inflammatory processes in a range of
      diseases. These whole blood assays can be employed to monitor activity in disease
      and perform in vitro and ex vivo assessment of chemokine receptor (CXCR)
      antagonists.

PMID- 16406724
TI  - The presence of GC-AG introns in Neurospora crassa and other euascomycetes
      determined from analyses of complete genomes: implications for automated gene
      prediction.
AB  - A combination of experimental and computational approaches was employed to
      identify introns with noncanonical GC-AG splice sites (GC-AG introns) within
      euascomycete genomes. Evaluation of 2335 cDNA-confirmed introns from Neurospora
      crassa revealed 27 such introns (1.2%). A similar frequency (1.0%) of GC-AG
      introns was identified in Fusarium graminearum, in which 3 of 292 cDNA-confirmed
      introns contained GC-AG splice sites. Computational analyses of the N. crassa
      genome using a GC-AG intron consensus sequence identified an additional 20
      probable GC-AG introns in this fungus. For 8 of the 47 GC-AG introns identified
      in N. crassa a GC donor site is also present in a homolog from Magnaporthe
      grisea, F. graminearum, or Aspergillus nidulans. In most cases, however, homologs
      in these fungi contain a GT-AG intron or no intron at the corresponding position.
      These findings have important implications for fungal genome annotation, as the
      automated annotations of euascomycete genomes incorrectly identified intron
      boundaries for all of the confirmed and probable GC-AG introns reported here.

PMID- 16406725
TI  - A microarray system for genotyping 150 single nucleotide polymorphisms in the
      coding region of human mitochondrial DNA.
AB  - We established a genotyping system for a panel of 150 SNPs in the coding regions
      of mitochondrial DNA based on multiplex tag-array minisequencing. We show the
      feasibility of this system for simultaneous identification of individuals and
      prediction of the geographical origin of the mitochondrial DNA population lineage
      of the sample donors by genotyping the panel of SNPs in 265 samples representing
      nine different populations from Africa, Europe, and Asia. Nearly 40,000 genotypes
      were produced in the study, with an overall genotyping success rate of 95% and
      accuracy close to 100%. The gene diversity value of the panel of 150 SNPs was
      0.991, compared to 0.995 for sequencing 500 nucleotides of the hypervariable
      regions I and II of mtDNA. For 17 individuals with identical sequences in the
      hypervariable regions of mtDNA, our panel of SNPs increased the power of
      discrimination. We observed 144 haplotypes that correspond to previously
      determined mitochondrial "haplogroups," and they allowed prediction of the origin
      of the maternal population lineage of 97% of the analyzed samples.

PMID- 16406726
TI  - High throughput DNA sequence variant detection by conformation sensitive
      capillary electrophoresis and automated peak comparison.
AB  - We report the development of a heteroduplex-based mutation detection method using
      multicapillary automated sequencers, known as conformation-sensitive capillary
      electrophoresis (CSCE). Our optimized CSCE protocol detected 93 of 95 known base
      substitution sequence variants. Since the optimization of the method, we have
      analyzed 215 Mb of DNA and identified 3397 unique variants. An analysis of this
      data set indicates that the sensitivity of CSCE is above 95% in the central 56%
      of the average PCR product. To fully exploit the mutation detection capacity of
      this method, we have developed software, canplot, which automatically compares
      normal and test results to prioritize samples that are most likely to contain
      variants. Using multiple fluorescent dyes, CSCE has the capacity to screen over
      2.2 Mb on one ABI3730 each day. Therefore this technique is suitable for projects
      where a rapid and sensitive DNA mutation detection system is required.

PMID- 16406728
TI  - The novel centrosomal associated protein CEP55 is present in the spindle midzone
      and the midbody.
AB  - Centrosomes are the major microtubule nucleating center in the cell; they also
      contribute to spindle pole organization and play a role in cell cycle progression
      as well as completing cytokinesis. Here we describe the molecular
      characterization of a novel human gene, CEP55, located in 10q23.33 that is
      expressed in multiple tissues and various cancer cell lines. Sequence analysis of
      the cDNA predicted a protein of 464 amino acids with several putative coiled-coil
      domains that are responsible for protein-protein interactions. Indeed, we found
      homodimerization of CEP55 by coimmunoprecipitation. Subcellular localization
      analysis revealed that endogenous CEP55 as well as an EGFP-CEP55 fusion protein
      is present at the centrosome throughout mitosis, whereas it also appears at the
      cleavage furrow in late anaphase and in the midbody in cytokinesis. Neither
      nocodazole nor taxol interfered with centrosome association of endogenous CEP55,
      suggesting that it directly interacts with centrosome components rather than with
      microtubules. In microtubule regrowth assays, overexpression of CEP55 did not
      enhance or inhibit microtubule nucleation. Together, these data suggest a
      possible involvement of CEP55 in centrosome-dependent cellular functions, such as
      centrosome duplication and/or cell cycle progression, or in the regulation of
      cytokinesis.

PMID- 16406727
TI  - Association of single-nucleotide polymorphisms in the suppressor of cytokine
      signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese.
AB  - Several previous linkage scans in type 2 diabetes (T2D) families indicated a
      putative susceptibility locus on chromosome 12q15-q22, while the underlying gene
      for T2D has not yet been identified. We performed a region-wide association
      analysis on 12q15-q22, using a dense set of >500 single-nucleotide polymorphisms
      (SNPs), in 1492 unrelated Japanese individuals enrolled in this study. We
      identified an association between T2D and a haplotype block spanning 13.6 kb of
      genomic DNA that includes the entire SOCS2 gene. Evolutionary-based haplotype
      analysis of haplotype-tagging SNPs followed by a "sliding window" haplotypic
      analysis indicated SNPs that mapped to the 5' region of the SOCS2gene to be
      associated with T2D with high statistical significance. The SOCS2 gene was
      expressed ubiquitously in human and murine tissues, including pancreatic beta
      cell lines. Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or
      isolated rat islets significantly suppressed glucose-stimulated insulin
      secretion. Our data indicate that SOCS2 may play a role in susceptibility to T2D
      in the Japanese.

PMID- 16406729
TI  - The role of FDG-PET, ictal SPECT, and MEG in the epilepsy surgery evaluation.
AB  - 2-[18F]Fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), ictal
      single-photon-emission computed tomography (ictal SPECT), and
      magnetoencephalography (MEG) represent three established functional imaging tests
      that offer unique information toward the localization of epilepsy for surgery
      evaluation and treatment. When these tests are combined with high-resolution
      magnetic fresonance imaging (MRI), epilepsy related structure and function
      disturbances may be localized with a degree of confidence and understanding not
      possible with electroencephalography (EEG), even ictal recordings with
      intracranial electrodes, the mainstay of tools for seizure localization. Use of
      these alternative tests allows an increased percentage of patients to be
      considered for surgical treatment. In particular, the additional information
      provided by these techniques has been demonstrated to help those patients with
      nonlocalizing MRI or extratemporal lobe epilepsy. Studies that address optimal
      use of these tests (alone and in combination) will build toward the next major
      advancement in the surgical treatment of epilepsy by allowing better patient
      selection, less risk, and better surgical outcomes. Ultimately, appropriate use
      of these tests, combined with more comprehensive functional brain mapping (e.g.,
      with MEG or functional MRI), may lead to completely noninvasive epilepsy surgery
      evaluation.

PMID- 16406731
TI  - [ASCUS: an update].
AB  - A report of ASCUS is always confusing or painful to the clinician, as
      histological correlate of this diagnosis is wide, ranging from a totally normal
      cervix mucosa to infiltrating carcinoma; most of the time it is the result of
      benign inflammatory or reactive changes. This is the reason why this category has
      evolved since its introduction in the Bethesda system for reporting cervical
      cytology in 1988, to achieve a closer link to the lesional diagnosis. The most
      recent modification took place in 2001, to subcategorize the ASC into ASC-US and
      ASC-H. The present review provides guidelines to manage these diagnoses.

PMID- 16406732
TI  - [Abdominal wall endometriosis after caesarean section: report of fifteen cases].
AB  - OBJECTIVE: Parietal endometriosis is an uncommon pathology. It can occur on all
      the scars, most often after a surgical procedure with hysterotomy. Surgical scar
      endometriosis following caesarean section has an incidence of 0.03 to 0.4%.
      PATIENTS AND METHODS: This retrospective study reviewed all the cases of parietal
      endometriosis seen during a 7-year period in the department of visceral surgery
      of the Armentiere's hospital center. A pathological analysis has confirmed each
      lesion retained. RESULTS: 15 women were treated during this period. The mean age
      is 32 years. All the women have one or two antecedents of caesarean with
      Pfannenstiel's laparotomy. The interval between the caesarean and the appearance
      of the first symptoms is on average of 5 years and 11 months. Only 66.6% of cases
      presented the classical symptoms with cyclic pain. For 66.6% of patients, the
      diagnosis of parietal endometriosis was suspected before the treatment. The
      treatment is a surgical one with exeresis for all the women. In 13.3% of the
      cases, the lesion is pre aponeurotic. In 46.6% of the cases, it overgrows the
      rectus abdominis muscle, in 33.3% of the cases the external abdominal oblique and
      at last a lesion overgrows the transversus abdominis and one is in an inguinal
      localization. The mean size of lesions is 2.48 cm. We have not notified
      complications and no recurrence was noted. DISCUSSION AND CONCLUSION: The local
      endometrial cell transplant is the most likely mechanism to explain the
      physiopathology of parietal endometriosis. The classical symptoms associate a
      painful swelling and cyclic pain related to the menstrual period, but all of
      these symptoms are not always associated. The contribution to the diagnosis of
      the imaging studies is weak. The surgical treatment has to be sufficiently wide
      to avoid all recurrence. No means of prevention has proved its efficiency. In
      26.6% of cases the parietal endometriosis is associated to pelvic endometriosis.
      This localization is more often asymptomatic. Then the realization of a
      laparoscopic exploration is not indicated immediately.

PMID- 16406733
TI  - [Uterine embolization for submucous fibroid: a bad alternative to surgery?].
AB  - A case of septic expulsion of a leiomyoma is reported 18 weeks after uterine
      artery embolisation (UAE). The patient underwent UAE for a symptomatic sub-mucous
      leiomyoma (type 2) of 5 cm. She was feverish and presented pelvic pain and
      purulent vaginal discharges. Vaginal examination revealed a necrotic mass
      prolapsed through the cervix that was carefully twisted out. Histopathologic
      examination showed extensive necrosis of the myomatous tissue. Microbiologic
      cultures showed heavy growth of Escherichia coli. Such findings challenge the
      interest and the safety of UAE for sub-mucous fibroids. Our case report stresses
      that uterine artery embolisation for submucous fibroids does not constitute,
      because of its risks, an alternative to conventional surgical treatment
      represented mainly by hysteroscopic resection.

PMID- 16406734
TI  - [Invasive lobular carcinoma of the breast: specific diagnosis and evolution].
AB  - Invasive lobular carcinoma accounts for 4 to 10% of breast cancers. The clinical
      and radiological diagnosis is difficult to make. Its progression is slower than
      that of ductal cancer, and the prognostic factors are more favourable. Its
      metastases are more frequently located in the digestive tract and the ovaries. It
      is more frequently bilateral. Its prognosis is not different from that of
      infiltrating ductal carcinomas. The choice of therapies depends on the individual
      characteristics of each patient and of the biological features of each tumour.
      However, lobular carcinomas seem to be less responsive to chemotherapy.

PMID- 16406735
TI  - [Young women with atypical endometrial hyperplasia or endometrial adenocarcinoma
      stage I: will conservative treatment allow pregnancy? Results of a French
      multicentric survey].
AB  - OBJECTIVES: To analyse the carcinological and obstetrical results of young women
      with atypical endometrial hyperplasia or endometrial adenocarcinoma, treated in a
      conservative way to allow pregnancy. PATIENTS AND METHODS: A retrospective
      analysis of 13 cases (5 adenocarcinomas and 8 atypical hyperplasias) followed in
      8 French centers between 1997 and 2004. RESULTS: After 4.6 months of conservative
      treatment, there were no residual lesions in 61.5% of the cases. Progestatives
      seem to be the most effective treatment. Tumoral regression makes it possible to
      plan a pregnancy, with childbirth in 25% of the cases. In these frequently
      infertile patients, all the techniques of assisted reproduction can be used.
      Recurrences are not rare after hormonal treatment (37.5%), so, total hysterectomy
      is justified after delivery. DISCUSSION AND CONCLUSION: Conservative treatment
      for young women with atypical endometrial hyperplasia or endometrial
      adenocarcinoma stage I can be considered in some cases to enable pregnancy.

PMID- 16406736
TI  - [Correct procedure in the presence of a fetal goiter associated with
      hypothyroidism. Observations from three cases].
AB  - Fetal goiter is a rare occurrence of which neonatal consequences are not always
      predictable. Concerning three cases of goiters associated with hypothyroidism
      discovered in utero, the authors describe the way to take care of in this bad
      codified situation. They insist upon the major role of ultrasound for goiter
      diagnosis and its impacts and for control of treatment efficiency. They also
      discuss intra amniotic L-Thyroxine injection and insist upon the necessity to
      obtain quick and definite thyroid evaluation after birth before decision to
      abstain from neonatal therapy.

PMID- 16406737
TI  - Acoustic analysis findings in objective laryngopharyngeal reflux patients.
AB  - OBJECTIVE: The aim of this study was to identify the effects of objective
      laryngopharyngeal reflux (LPR) on the acoustic parameters of patients by
      comparing their voice samples with that of control subjects. STUDY DESIGN:
      Prospective study in two tertiary reference hospitals. METHODS: 48 consecutive
      patients with symptoms related to LPR and 64 control subjects were included in
      the study. Suspected LPR patients underwent a 24-hour ambulatory pH monitoring,
      and 25 (52%) of them were shown to have objective LPR. Acoustical evaluation
      results of objective LPR patients were compared with that of symptomatic LPR
      patients and control subjects. RESULTS: All frequency perturbation values
      obtained from objective and symptomatic LPR patients were higher than the control
      subjects (P<0.01). Mean fundamental frequency, amplitude perturbation measures,
      and noise-to-harmonics ratio were not significantly different between groups.
      CONCLUSION: LPR patients have significantly different frequency perturbation
      values than control subjects.

PMID- 16406738
TI  - Halogen substitution of DNA protects from poisoning of topoisomerase II that
      results in DNA double-strand breaks.
AB  - DNA topoisomerase II (topo II), a fundamental nuclear enzyme, cleaves the double
      stranded DNA molecule at preferred sequences within its recognition/binding
      sites. We have recently reported [F. Cortes, N. Pastor, S. Mateos, I. Dominguez,
      The nature of DNA plays a role in chromosome segregation: endoreduplication in
      halogen-substituted chromosomes, DNA Repair 2 (2003) 719-726] that when cells
      incorporate halogenated nucleosides analogues of thymidine into DNA, it
      interferes with normal chromosome segregation, as shown by an extraordinarily
      high yield of endoreduplication. The frequency of endoreduplicated cells
      paralleled the level of analogue substitution into DNA, lending support to the
      idea that thymidine analogue substitution into DNA is most likely responsible for
      the triggering of endoreduplication. Using the pulsed-field gel electrophoresis
      (PFGE) technique, we have now analyzed a possible protection provided by the
      incorporation of exogenous halogenated nucleosides against DNA breakage induced
      by the topo II poison m-AMSA. The result was that the different halogenated
      nucleosides were shown as able to protect DNA from double-strand breaks induced
      by m-AMSA depending such a protection upon the relative percent of incorporation
      of a given thymidine analogue into DNA. Our results clearly indicate that the
      presence of halogenated nucleosides in DNA diminishes the frequency of
      interaction of topo II with DNA and thus the frequency with which cleavage can
      occur.

PMID- 16406739
TI  - Distinguishing fall activities from normal activities by angular rate
      characteristics and high-speed camera characterization.
AB  - Distinguishing sideways and backward falls from normal activities of daily living
      using angular rate sensors (gyroscopes) was explored in this paper. Gyroscopes
      were secured on a shirt at the positions of sternum (S), front of the waist (FW)
      and right underarm (RU) to measure angular rate in lateral and sagittal planes of
      the body during falls and normal activities. Moreover, the motions of the fall
      incidents were captured by a high-speed camera at a frame rate of 250 frames per
      second (fps) to study the body configuration during fall. The high-speed camera
      and the sensor data capture system were activated simultaneously to synchronize
      the picture frame of high-speed camera and the sensor data. The threshold level
      for each sensor was set to distinguish fall activities from normal activities.
      Lead time of fall activities (time after threshold value is surpassed to the time
      when the hip hits the ground) and relative angle of body configuration (angle
      beta between the vertical line and the line from the center point of the foot or
      the center point between the two legs to that of the waist) at the threshold
      level were studied. For sideways falls, lead times of sensors at positions FW and
      S were about 200-220ms and 135-182ms, respectively. The lead time of the slippery
      backward fall (about 98ms) from the sensor at position RU was shorter than that
      of the sideways falls from the sensors at positions FW and S. The relative angle
      of body configuration at threshold level for sideways and backward falls were
      about 40-43 degrees for the sensor at position FW, about 43-52 degrees for the
      sensor at position S and about 54 degrees for the sensor at position RU,
      respectively. This is the first study that investigates fall dynamics in
      detection of fall before the person hits the ground using angular rate sensors
      (gyroscopes).

PMID- 16406740
TI  - Does gender affect pulmonary function and exercise capacity?
AB  - It is well established that women exhibit several anatomic and physiologic
      characteristics that distinguish their responses to exercise from those of men.
      These factors have been shown to influence the training response and contribute
      to lower maximal aerobic power in women. Additionally, the reproductive hormones,
      estrogen and progesterone, can influence ventilation, substrate metabolism,
      thermoregulation, and pulmonary function during exercise. Pulmonary structural
      and morphologic differences between genders include smaller vital capacity and
      maximal expiratory flow rates, reduced airway diameter, and a smaller diffusion
      surface than age- and height-matched men. These differences may have an effect on
      the integrated ventilatory response, respiratory muscle work, and in pulmonary
      gas exchange during exercise. Specifically, recent evidence suggests that during
      heavy exercise, women demonstrate greater expiratory flow limitation, an
      increased work of breathing, and perhaps greater exercise induced arterial
      hypoxemia compared to men. The consequence of these pulmonary effects has the
      potential to adversely affect aerobic capacity and exercise tolerance in women.

PMID- 16406741
TI  - Clinical cough and its mechanisms.
AB  - Cough is the commonest symptom of clinical importance and the most frequent
      reason for new consultations with a doctor. Although therapy directed at any
      underlying cause for cough can be effective there is a clinical need for new
      treatments specifically directed at the cough itself. A major obstacle to the
      development of such therapy has been an imprecise understanding of the
      pathophysiological mechanisms responsible for cough. In this article, we review
      the important clinical aspects of both acute and chronic cough, offer practical
      insight into the existing treatment options, highlight the current understanding
      of cough pathophysiology and identify important areas for future research effort.

PMID- 16406742
TI  - Current and future peripherally-acting antitussives.
AB  - Cough is among the most common complaints for which medical evaluation is sought.
      The clinical significance of this problem is evidenced by the enormous financial
      expenditure on prescription and non-prescription cough remedies worldwide.
      Centrally-acting antitussive agents, such as opiates, are often associated with
      undesirable or intolerable side effects, including sedation, nausea, and
      constipation. Therefore, safe and effective peripherally-acting antitussive
      agents are particularly desirable. Relatively few commercially-available products
      suppress cough through a peripheral mechanism of action. Recent research in the
      field of cough has resulted in the development of several new classes of
      compounds that may prove to be clinically useful peripherally-acting
      antitussives.

PMID- 16406743
TI  - Practical prescribing and long-term efficacy and safety of zonisamide.
AB  - Long-term efficacy, tolerability and safety of antiepileptic drug (AED) therapy
      is essential given the chronic nature of epilepsy. Zonisamide (Zonegran), a novel
      AED with a broad range of mechanisms of action contributing to its antiseizure
      efficacy, has been evaluated extensively for the long-term management of
      epilepsy. Open-label extension studies in the United States and Europe suggest
      continued efficacy of zonisamide in long-term treatment without development of
      adverse events further to those seen in registration studies. Baseline seizure
      frequency is reduced by approximately 40-70% during long-term treatment for up to
      2 years, and 30-50% of patients attain >or=50% reduction in seizure frequency
      across all categories of seizure and durations of treatment. Preliminary data
      indicate a progressive decline in seizure frequency with continued zonisamide
      treatment. Zonisamide is well tolerated in long-term use, with a trend towards
      decreasing incidence of generally mild adverse events over time and a low rate of
      withdrawal during chronic use. Nephrolithiasis and other serious adverse events
      are infrequent, and can be minimised by appropriate management and patient
      education. This profile of maintained efficacy, tolerability and safety during
      sustained administration in combination with other AEDs supports zonisamide as a
      valuable adjunctive agent in the long-term management of refractory partial
      epilepsy.

PMID- 16406744
TI  - Effects of randomization methods on statistical inference in disease cluster
      detection.
AB  - Monte Carlo methods are commonly used to assess the statistical significance of
      disease clusters. This usually involves permuting the observed outcome measure,
      such as the rate of disease, across the geographic units within the study area.
      When the variance of the disease rates is heterogeneous, however, randomizing the
      disease rate across the geographic units results in over-estimating the p-values
      in areas of low variance and under-estimating the p-values in areas of high
      variance. This bias results in under-ascertainment of clusters in urban areas and
      over-ascertainment of clusters in rural areas. As an alternative, randomizing the
      number of cases of disease or deaths proportional to the population at risk
      preserves the variance structure of the study area, therefore resulting in
      unbiased statistical inference. We compare results from randomizing rates with
      those from randomizing case counts, using county-level prostate cancer mortality
      data for the United States and ZIP-Code level prostate cancer incidence data for
      New York State, using the local Moran's I statistic.

PMID- 16406745
TI  - Optimized PCR fragments for heteroduplex analysis of the whole human
      mitochondrial genome with denaturing HPLC.
AB  - Denaturing high pressure liquid chromatography (dHPLC) is an efficient method for
      discovery of unknown mutations by heteroduplex analysis of PCR fragments. For
      comprehensive mutation scanning of the whole 16.569 bp human mitochondrial
      genome, we developed a set of 67 primer pairs defining overlapping PCR fragments
      that are well suited for heteroduplex analysis. The aim of our optimization
      efforts was to ensure that point mutations are detectable at every nucleotide
      position of each amplicon. Some GC-rich regions of mitochondrial DNA (mtDNA) were
      found to have unfavourable melting profiles in all possible amplicons, therefore
      requiring GC-clamps at the end of one or both oligonucleotide PCR primers.
      Following detection of a heteroduplex pattern by dHPLC, our primers can also be
      employed for DNA sequencing to identify the underlying mutation. In case of
      heteroplasmic mutations with a low proportion of mutant mtDNA, a fragment
      collector is useful to recover the heteroduplex peak, which contains mutant and
      wildtype DNA molecules in a 1:1 ratio.

PMID- 16406746
TI  - Sensitive column-switching high-performance liquid chromatography method for
      determination of propiverine in human plasma.
AB  - A sensitive column-switching high-performance liquid chromatography (HPLC) with
      ultraviolet (UV) detection was developed for the determination of propiverine in
      human plasma. Propiverine and internal standard, oxybutynin, were extracted from
      human plasma that had been made basic with 5N sodium hydroxide into methyl tert
      butyl ether. The extracted plasma sample was injected onto the HPLC system
      consisting of a pretreatment column, a concentrating column, and an analytical
      column, which were connected with a six-port switching valve. The assay was
      linear in concentration ranges of 2-200 ng/ml for propiverine in human plasma.
      This method showed excellent sensitivity (a limit of detection of 0.5 ng/ml),
      good precision and accuracy. This method is suitable for bioequivalence studies
      following single dose in healthy volunteers.

PMID- 16406748
TI  - Capillary electrophoresis screening of poisonous anions extracted from biological
      samples.
AB  - A method was developed for screening human biological samples for poisonous
      anions using capillary electrophoresis (CE) employing indirect UV detection. The
      run buffer consisted of 2.25 mM pyromellitic acid, 1.6 mM triethanolamine, 0.75
      mM hexamethonium hydroxide and 6.5mM NaOH at pH 7.7. Biological samples were
      pretreated using solid phase extraction. The method was applied to the analysis
      of human blood, plasma, urine, and intestinal contents. Twenty-nine different
      anions were detectable at aqueous concentrations of 1 part per million (ppm) with
      a typical analysis time less than 20 min. Intraday migration time R.S.D. and peak
      area R.S.D. for blood samples were less than 1.1% and 6.3%, respectively.
      Interday migration time R.S.D. for plasma samples ranged from 7.5% to 10.4%. The
      new method produced efficient separations of various target anions extracted from
      complex biological matrices.

PMID- 16406747
TI  - Neurochemical analysis of amino acids, polyamines and carboxylic acids: GC-MS
      quantitation of tBDMS derivatives using ammonia positive chemical ionization.
AB  - The GC-MS quantitation of a large number of neurochemicals utilizing a single
      derivatization step is not common but is provided by the reagent N-(tert
      butyldimethylsilyl)-N-methyltrifluro-acetamide (MTBSTFA). Previous workers have
      utilized this derivative for GC-MS analyses of amino acids, carboxylic acids and
      urea with electron impact (EI) and with positive chemical ionization (PCI;
      methane as reagent gas). However, these conditions yield significant
      fragmentation, decreasing sensitivity and in some cases reducing specificity for
      quantitation with selected ion monitoring (SIM). Additionally, the majority of
      studies have used a single internal standard to quantitate many compounds. In
      this study we demonstrate that using isotopic dilution combined with ammonia as
      the reagent gas for PCI analyses, results in high precision and sensitivity in
      analyzing complex neurochemical mixes. We also demonstrate for the first time the
      utility of this derivative for the analysis of brain polyamines and the dipeptide
      cysteinyl glycine. In the case of ammonia as the reagent gas, all amino acids,
      polyamines and urea yielded strong [MH](+) ions with little or no fragmentation.
      In the case of carboxylic acids, [M+18](+) ions predominated but [MH](+) ions
      were also noted. This approach was used to analyze superfusates from hippocampal
      brain slices and brain tissue extracts from brain lesion studies. The advantages
      of this methodology include: (i) simple sample preparation; (ii) a single
      derivatization step; (iii) direct GC-MS analysis of the reaction mix; (iv) high
      precision as a result of isotopic dilution analyses; (v) high sensitivity and
      specificity as a result of strong [MH](+) ions with ammonia reagent gas; (vi) no
      hydrolysis of glutamine to glutamate or asparagine to aspartate; and (vii)
      applicability to a wide range of neurochemicals.

PMID- 16406749
TI  - The hair growth promoting effect of ascorbic acid 2-phosphate, a long-acting
      Vitamin C derivative.

PMID- 16406750
TI  - Glucose inhibits the expression of triose phosphate/phosphate translocator gene
      in wheat via hexokinase-dependent mechanism.
AB  - Although triose phosphate/phosphate translocator is known to play an important
      role in regulating the distribution of assimilates in wheat chloroplasts, the
      mechanism of triose phosphate/phosphate translocator gene control has not yet
      been clearly elucidated. We first showed that glucose inhibited the expression of
      triose phosphate/phosphate translocator gene in wheat by reverse transcription
      polymerase chain reaction and Western blotting. The triose phosphate/phosphate
      translocator expression was seriously impaired by 5 mmol/L glucose, and it
      responded slowly, more than 48 h, to level as low as 1 mmol/L glucose. Both
      glucose and 2-deoxyglucose inhibited the expression of triose phosphate/phosphate
      translocator gene, but 2-deoxyglucose-6-P, product of phosphorylated 2
      deoxyglucose, cannot be further metabolized, therefore the further metabolism of
      phosphorylated glucose by hexokinase is not a prerequisite for triggering glucose
      regulated expression of triose phosphate/phosphate translocator gene. Glucose had
      little inhibitory effect on the expression of triose phosphate/phosphate
      translocator gene when hexokinase activity was reduced or eliminated by
      transforming wheat protoplasts with a hexokinase antisense construct or treating
      protoplasts with glucosamine, an inhibitor of hexokinase. Therefore, it appears
      essential for hexokinase to retain phosphorylation activity for glucose to
      regulate the expression of triose phosphate/phosphate translocator gene. The
      treatment of protoplasts with glucose-6-phosphate resulting in no inhibition of
      triose phosphate/phosphate translocator expression demonstrated that
      phosphorylation via hexokinase is necessary for glucose inhibiting triose
      phosphate/phosphate translocator expression. All the data suggest that triose
      phosphate/phosphate translocator is regulated by glucose via a hexokinase
      dependent pathway.

PMID- 16406751
TI  - Induction of apoptotic cell death by putrescine.
AB  - The polyamines are essential for cellular growth and differentiation. Ornithine
      decarboxylase (ODC), which catalyses the first step in the biosynthesis of the
      polyamines, has a very fast turnover and is subject to a strong feedback control
      by the polyamines. In the present study, we show that overexpression of a
      metabolically stable ODC in CHO cells induced a massive cell death unless the
      cells were grown in the presence of the ODC inhibitor alpha
      difluoromethylornithine (DFMO). Cells overexpressing wild-type (unstable) ODC, on
      the other hand, were not dependent on the presence of DFMO for their growth. The
      induction of cell death was correlated with a dramatic increase in cellular
      putrescine levels. Analysis using flow cytometry revealed perturbed cell cycle
      kinetics, with a large accumulation of cells with sub-G1 amounts of DNA, which is
      a typical sign of apoptosis. Another strong indication of apoptosis was the
      finding that one of the key enzymes in the apoptotic process, caspase-3, was
      induced when DFMO was omitted from the growth medium. Furthermore, inhibition of
      the caspase activity significantly reduced the recruitment of cells to the sub-G1
      fraction. In conclusion, deregulation of polyamine homeostasis may negatively
      affect cell proliferation and eventually lead to cell death by apoptosis if
      putrescine levels become too high.

PMID- 16406752
TI  - Binding studies of hydantoin racemase from Sinorhizobium meliloti by calorimetric
      and fluorescence analysis.
AB  - Hydantoin racemase enzyme together with a stereoselective hydantoinase and a
      stereospecific d-carbamoylase guarantee the total conversion from d,l-5
      monosubstituted hydantoins with a low velocity of racemization, to optically pure
      d-amino acids. Hydantoin racemase from Sinorhizobium meliloti was expressed in
      Escherichia coli. Calorimetric and fluorescence experiments were then carried out
      to obtain the thermodynamic binding parameters, deltaG, deltaH and DeltaS for the
      inhibitors L- and D-5-methylthioethyl-hydantoin. The number of active sites is
      four per enzyme molecule (one per monomer), and the binding of the inhibitor is
      entropically and enthalpically favoured under the experimental conditions
      studied. In order to obtain information about amino acids involved in the active
      site, four different mutants were developed in which cysteines 76 and 181 were
      mutated to Alanine and Serine. Their behaviour shows that these cysteines are
      essential for enzyme activity, but only cysteine 76 affects the binding to these
      inhibitors.

PMID- 16406753
TI  - Surface planar bilayers of phospholipids used in protein membrane reconstitution:
      an atomic force microscopy study.
AB  - In this work, using atomic force microscopy (AFM), we have studied the influence
      of the temperature on the properties of the surface planar bilayers (SPBs) formed
      with: (i) the total lipid extract of Escherichia coli; (ii) 1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphocholine (POPC) and 1,2-dimyristoyl-sn-glycero-3
      phosphoethanolamine (DMPC) (1:1, mol/mol); and, 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanol-amine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol
      (POPG) (3:1, mol/mol). According to the height profile analysis we performed, the
      height of the SPBs of DMPC:POPC were temperature dependent. Separated domains
      were observed in the SPBs of the POPE:POPG mixture and the E. coli lipid extract.
      The implication of those domains for the correct insertion of membrane proteins
      into proteoliposomes is discussed.

PMID- 16406754
TI  - Crosstalk.

PMID- 16406755
TI  - The structural basis of non-photochemical quenching is revealed?
AB  - Light-harvesting complex II (LHCII, the major plant light-harvesting pigment
      protein complex, efficiently harvests light-energy. However, if the incident
      light intensity is too high and photosynthesis becomes saturated, LHCII can
      switch into a quenching state that prevents photodamage. This important process
      is called non-photochemical quenching, or NPQ, and represents feedback control.
      Andrew Pascal et al. have recently proposed a detailed model of NPQ based upon
      the crystal structure of LHCII from spinach.

PMID- 16406756
TI  - Turning ON the switch--RhoGEFs in plants.
AB  - Plant ROPs (or RACs) are Ras-related, small GTP-binding proteins that function as
      molecular switches in numerous signaling cascades. ROPs (RACs) cycle between a
      GDP-bound, inactive state and a GTP-bound, active state. Activation requires
      guanine-nucleotide exchange factors (GEFs), which were not identified in plants
      until recently. Alfred Wittinghofer and co-workers' description of a group of
      plant-specific RhoGEFs opens the way for the elucidation of ROP signaling
      cascades from membrane receptors to responses.

PMID- 16406757
TI  - Nasal continuous positive airway pressure with heliox in infants with acute
      bronchiolitis.
AB  - This is the first study aiming to assess the effects of heliox in combination
      with nasal continuous positive airway pressure (Hx-nCPAP) as a rescue treatment
      in infants with refractory acute bronchiolitis. Fifteen out of 78 infants with
      acute bronchiolitis consecutively admitted to PICU fulfilled the inclusion
      criteria: clinical score>or=5 or arterial oxygen saturation (SatO2)<or=92% or
      PCO2>50 mmHg, despite supportive therapy, nebulized L-epinephrine, and heliox
      therapy through non-rebreathing reservoir facemask. Hx-nCPAP was added as a
      rescue treatment. Baseline mean (standard deviation) values were: clinical score
      of 7.4 (1.2) points; PCO2 of 63.8 (12) mmHg; respiratory rate (RR) of 66.4 (9.9);
      and SatO2 of 88.6 (4.7)%. Clinical score, PCO2, RR and SatO2 improved during the
      study time (P<0.05). After 1 h the mean clinical score decreased by 1.5 points,
      with a total average decrease of 3.5 points at the end of the study period. The
      mean PCO2 diminished by 9 and 25 mmHg, after 1 and 48 h, respectively. The mean
      RR decreased 13 rpm after 1 h and 30 rpm after 48 h. The Hx-nCPAP total duration
      ranged from 2 to 14 days. Only one patient required endotracheal intubation. No
      adverse effects were detected. All patients recovered fully. In conclusion, Hx
      nCPAP improved the clinical score, decreased the tachypnea and enhanced the CO2
      elimination of infants with refractory acute bronchiolitis within 1h of
      administration, in a safe and non-invasive manner. Hx-nCPAP might reduce the need
      for endotracheal intubation. Further studies are needed.

PMID- 16406758
TI  - Partial intestinal obstruction caused by a lipoma within a Meckel's diverticulum.

PMID- 16406759
TI  - Forward inference using functional neuroimaging: dissociations versus
      associations.
AB  - Many people are excited by functional neuroimaging as a new tool for cognitive
      science; many others are sceptical. In this opinion article, I describe a
      'forward inference' that one can make from patterns of brain activity to
      distinguish between cognitive theories. I give an example of forward inferences
      in research on recognition memory, and outline some statistical criteria for a
      'qualitative difference' in brain activity. Forward inferences resemble the
      dissociation logic long-used in behavioural studies of healthy and brain-damaged
      people, although I argue that dissociations in neuroimaging data can go beyond
      behavioural dissociations. Nonetheless, forward inferences are only as good as
      the cognitive theories to which they pertain, and are most valuable in
      conjunction with other types of inference.

PMID- 16406760
TI  - Can cognitive processes be inferred from neuroimaging data?
AB  - There is much interest currently in using functional neuroimaging techniques to
      understand better the nature of cognition. One particular practice that has
      become common is 'reverse inference', by which the engagement of a particular
      cognitive process is inferred from the activation of a particular brain region.
      Such inferences are not deductively valid, but can still provide some
      information. Using a Bayesian analysis of the BrainMap neuroimaging database, I
      characterize the amount of additional evidence in favor of the engagement of a
      cognitive process that can be offered by a reverse inference. Its usefulness is
      particularly limited by the selectivity of activation in the region of interest.
      I argue that cognitive neuroscientists should be circumspect in the use of
      reverse inference, particularly when selectivity of the region in question cannot
      be established or is known to be weak.

PMID- 16406761
TI  - Estimation of landfill emission lifespan using process oriented modeling.
AB  - Depending on the particular pollutants emitted, landfills may require service
      activities lasting from hundreds to thousands of years. Flexible tools allowing
      long-term predictions of emissions are of key importance to determine the nature
      and expected duration of maintenance and post-closure activities. A highly
      capable option represents predictions based on models and verified by experiments
      that are fast, flexible and allow for the comparison of various possible
      operation scenarios in order to find the most appropriate one. The intention of
      the presented work was to develop a experimentally verified multi-dimensional
      predictive model capable of quantifying and estimating processes taking place in
      landfill sites where coupled process description allows precise time and space
      resolution. This constitutive 2-dimensional model is based on the macromechanical
      theory of porous media (TPM) for a saturated thermo-elastic porous body. The
      model was used to simulate simultaneously occurring processes: organic phase
      transition, gas emissions, heat transport, and settlement behavior on a long time
      scale for municipal solid waste deposited in a landfill. The relationships
      between the properties (composition, pore structure) of a landfill and the
      conversion and multi-phase transport phenomena inside it were experimentally
      determined. In this paper, we present both the theoretical background of the
      model and the results of the simulations at one single point as well as in a
      vertical landfill cross section.

PMID- 16406763
TI  - Pharmacological therapy of Paget's and other metabolic bone diseases.
AB  - Paget's disease is a relatively common high-turnover metabolic bone disease that
      can serve as a model for osteoporosis and other metabolic bone diseases in
      investigation of therapeutic strategies to normalize bone turnover. Aims of
      treatment include rapid normalization of bone formation and resorption to prevent
      loss of mechanical integrity. Treatment will also reduce pain, while long-term
      maintenance of normal turnover may prevent long-term complications. Newer
      bisphosphonates have high antiresorptive potency and increased retention in bone,
      permitting a strategy of intermittent intravenous (IV) administration in
      achieving and maintaining normal bone turnover. In pivotal zoledronic acid
      Paget's disease trials, patients received a single 15-min IV infusion of
      zoledronic acid 5 mg (ZOL 5 mg) or risedronate 30 mg/day orally for 2 months.
      Treatment with ZOL 5 mg was associated with significant improvement in serum
      alkaline phosphatase, normalization in both the short and long term, and
      significant prolongation of biochemical therapeutic response in long-term follow
      up. No changes in serum creatinine levels were observed with either treatment,
      and no clinically significant renal abnormalities were reported. Intermittent IV
      administration of potent bisphosphonates constitutes an intriguing strategy for
      treatment of Paget's disease and other metabolic bone diseases.

PMID- 16406762
TI  - Soy moderately improves microstructural properties without affecting bone mass in
      an ovariectomized rat model of osteoporosis.
AB  - Soy protein is reported to prevent bone loss in both women and rat models of
      osteoporosis. However, the role of soy isoflavones on the trabecular
      microarchitectural properties needs to be explored. In the present study, we
      examined whether soy protein with graded doses of isoflavones reverses loss of
      bone mineral density (BMD), bone mineral content (BMC), and trabecular
      microstructure in an ovariectomized (Ovx) osteopenic rat model. Seventy-eight 9-m
      old female Sprague-Dawley rats were either sham-operated (Sham; 1 group) or Ovx
      (5 groups) and fed a semi-purified casein-based diet. After 90 days, the
      occurrence of bone loss was confirmed using dual energy X-ray absorptiometry.
      Thereafter, rats were assigned to the following treatments: Sham, Ovx (control),
      Ovx + 17beta-estradiol (E(2); 10 microg/kg body wt. twice per week), Ovx + soy
      protein depleted of isoflavones (Soy-; 0.06 mg isoflavones/g protein), Ovx + soy
      protein with normal isoflavone content (Soy; 3.55 mg isoflavones/g protein), and
      Ovx + isoflavone-enriched soy protein (Soy+; 7.10 mg isoflavones/g protein).
      After 125 days of treatment, rats were euthanized, and tibia and lumbar bones
      were collected for the assessment of BMD, BMC, and trabecular microarchitectural
      properties using X-ray microcomputed tomography. None of the treatments had an
      effect on BMD or microarchitectural properties of the lumbar vertebra. However,
      Soy treatment significantly increased tibial BMC and BMD by 10% and 4.5% compared
      with Ovx control, but the increase in BMD was not enough to reach the BMD levels
      of the Sham control group. The Soy+ diet positively affected the tibial
      architectural properties including trabecular thickness, separation, and number.
      In summary, our findings suggest that soy protein does not restore bone loss in
      osteopenic rats; however, higher doses of isoflavones may be required to reverse
      the loss of tibial microstructural properties.

PMID- 16406764
TI  - Cyclical changes of vertebral body heights and bone loss in healthy women after
      menopause.
AB  - Annual changes in vertebral body heights (VHs) and lumbar bone mineral density
      (LBMD) were evaluated in 120 healthy pre- and post-menopausal women aged 45-74
      years. Subjects were divided into groups according to menstrual status and years
      since menopause (YSM). Vertebral heights were evaluated, using radiological
      morphometry as the sum of anterior vertebral body heights (AVHs) from T4 to L5 at
      baseline and exactly 12 months later. Results indicate that the sum of VHs is
      inversely correlated with advancing age, and the decrease in VHs is not a
      constant process over time but rather exhibits cyclical damping oscillations.
      When log-linear trend of VH decrease was transformed into a constant considering
      annual percentage changes, the presence of a cyclical component of 7 years was
      evident. Employing a harmonic regression model, the cyclical component was also
      statistically significant on baseline data. The cyclical decrease of VHs
      corresponds to an analogous cyclical behavior of LBMD values. These results
      suggest that a lack of estrogen acts as a synchronizer on bone remodeling,
      triggering a latent cyclical rhythm of bone loss, accompanied by cyclical bone
      microarchitecture deterioration and consequent vertebral body deformities, which
      after menopause persists throughout life. The existence of a chronobiological
      rhythm of bone loss and trabecular bone strength reduction at vertebral level
      after menopause, if confirmed, could have important clinical implications.

PMID- 16406766
TI  - Transcending the biomarker mindset: deciphering disease mechanisms at the single
      cell level.
AB  - The application of proteomics to disease research promises to enhance the
      understanding and treatment of many human maladies through the identification of
      molecular profiles associated with each disease. However, although much is made
      of the utility of molecular signatures as markers of disease state, insufficient
      emphasis is often placed on the simultaneous need for biological mechanism
      inquiry. Focused and detailed analyses of disease-associated signaling networks
      have the potential to be more mechanistically informative than large-scale
      proteomic profiling approaches, providing insight into the cellular processes
      involved in pathogenesis, disease progression and therapeutic resistance; while
      still providing diagnostic or clinical management direction. Phospho-specific
      flow cytometry provides a method for the analysis of pathological signaling
      networks, enabling the investigation of disease mechanisms at the single-cell
      level.

PMID- 16406767
TI  - Antigen arrays for antibody profiling.
AB  - Antigen array technologies enable large-scale profiling of the specificity of
      antibody responses against autoantigens, tumor antigens and microbial antigens.
      Antibody profiling will provide insights into pathogenesis, and will enable
      development of novel tests for diagnosis and guiding therapy in the clinic.
      Recent advances in the field include development of antigen array-based
      approaches to examine immune responses against antigens encoded in genetic
      libraries, post-translationally modified proteins, and other biomolecules such as
      lipids. A promising application is the use of antibody profiling to guide
      development and selection of antigen-specific therapies to treat autoimmune
      disease. This review discusses these advances and the challenges ahead for
      development and refinement of antibody profiling technologies for use in the
      research laboratory and the clinic.

PMID- 16406768
TI  - Two-dimensional mass spectrometric mapping.
AB  - The identification and relative quantification of proteins in closely related
      biological samples is the backbone for many investigations in systems biology and
      for the discovery of biomarkers. While two-dimensional gel-based methodologies
      are still widely used for comparative proteomic studies, the recent advent of gel
      free methodologies may allow the analysis of a larger number of samples in an
      automated fashion. Most of the technologies presented in this review require a
      chemical modification of proteins before analysis, and rely on the relative
      intensities of mass spectrometry signals for protein quantification. In
      particular, two-dimensional mass spectrometric mapping methodologies provide a
      visual representation of mass spectrometric data, thus facilitating the
      identification of differences in relative protein abundance.

PMID- 16406769
TI  - Altering protein turnover in tumor cells: new opportunities for anti-cancer
      therapies.
AB  - The promising effects of the proteasome inhibitor bortezomib (Velcade, PS-341) in
      the treatment of certain types of cancer have fired up the interest on this
      multicatalytic proteolytic machinery. A number of recent reviews thoroughly
      describe various aspects of the ubiquitin-proteasome system and its importance in
      the control of cell growth and tumorigenesis. Here, we will focus on recent data
      unveiling a link between the proteasome and some elements of the apoptotic
      machinery including Bcl-2 members, caspases, IAPs and IAP antagonists. Perturbing
      their turnover significantly contributes to the apoptotic response and the anti
      neoplastic activity of proteasome inhibitors.

PMID- 16406770
TI  - The xenoestrogen bisphenol A in the Hershberger assay: androgen receptor
      regulation and morphometrical reactions indicate no major effects.
AB  - We evaluated androgen-like effects of bisphenol A (BPA) using orchiectomized
      Wistar rats. Animals were treated p.o. either with vehicle or with 3, 50, 200,
      500 mg/kgbw/day BPA (n=13) for 7 days. One group was treated s.c. with
      1mg/kgbw/day testosterone propionate (TP). Flutamide (FL) (3mg/kgbw/day, p.o.)
      was used to antagonize androgen effects of the suprapharmacological dose (500
      mg/kgbw/day) of BPA. Androgen-like effects of BPA on prostates and seminal
      vesicles were assessed by the Hershberger assay, densitometric analysis of
      androgen receptor (AR) immunoreactivity, cell proliferation-index and a
      morphometric analysis. Absolute weights of prostates and seminal vesicles were
      not increased by BPA, whereas the relative weights were increased at higher doses
      of BPA, most likely due to a decrease in body weight. Staining intensity for AR
      immunoreactivity was increased at low but not at higher doses of BPA in
      comparison to the orchiectomized rats. BPA at all doses tested did not cause an
      increase of the cell proliferation-index. Epithelial height and glandular luminal
      area were increased by low doses of BPA, whereas higher doses caused a decrease
      of these parameters. The data provide evidence that BPA does not exert major
      androgenic effects.

PMID- 16406771
TI  - How does Pasteurella multocida respond to the host environment?
AB  - Pasteurella multocida is a Gram-negative bacterial pathogen, which causes
      diseases of economic importance in a wide range of animal species. The response
      of P. multocida to the host environment has been analysed at the transcription
      level, using DNA microarrays, and at the protein-expression level, using
      proteomics techniques. Furthermore, a growing number of P. multocida-directed
      mutants have been assessed for their ability to cause disease. Although technical
      impediments mean that it is currently difficult to analyse bacterial responses at
      the earliest stages of infection, it is clear that during later stages of
      infection the bacteria encounter host niches that require them to modify the
      expression of genes involved in central energy metabolism and in the uptake of
      various nutrients such as iron and amino acids. Furthermore, in vitro experiments
      have defined the varying bacterial responses to low iron and to different iron
      sources, including haemoglobin and transferrin. To date, most P. multocida genes
      shown to be upregulated during infection are involved in nutrient acquisition and
      metabolic processes, indicating that true virulence genes might be constitutively
      expressed, upregulated only during initial stages of infection or upregulated at
      levels below current detection limits.

PMID- 16406773
TI  - Adaptation of Legionella pneumophila to the host environment: role of protein
      secretion, effectors and eukaryotic-like proteins.
AB  - The intracellular pathogen Legionella pneumophila has evolved sophisticated
      mechanisms that enable it to subvert host functions, enter, survive and replicate
      in amoebae or alveolar macrophages, and to finally evade these hosts. Protozoa
      are essential for the growth of Legionella and the interaction with amoeba seems
      to be the driving force in the evolution of its pathogenicity. This is reflected
      in the genome of this pathogen, which encodes a high number and variety of
      eukaryotic-like proteins that are able to interfere in the various steps of the
      infectious cycle by mimicking functions of eukaryotic proteins. Central to the
      pathogenicity of L. pneumophila are the many secretion systems delivering these
      and other effectors to the host cell. Recent studies have highlighted the multi
      functional role of these factors secreted by L. pneumophila, in host-pathogen
      interactions.

PMID- 16406772
TI  - Subversion of actin dynamics by EPEC and EHEC.
AB  - During the course of infection, enteropathogenic and enterohaemorrhagic
      Escherichia coli (EPEC and EHEC, respectively) subvert the host cell signalling
      machinery and hijack the actin cytoskeleton to tighten their interaction with the
      gut epithelium, while avoiding phagocytosis by professional phagocytes. Much
      progress has been made recently in our understanding of how EPEC and EHEC
      regulate the pathways leading to local activation of two regulators of actin
      cytoskeleton dynamics, the Wiskott-Aldrich syndrome protein (N-WASP) and the
      Arp2/3 complex. A recent highlight is the unravelling of functions for effector
      proteins (particularly Tir, TccP, Map and EspG/EspG2) that are injected into the
      host cell by a type III secretion system.

PMID- 16406774
TI  - Bacterial evasion of the autophagic defense system.
AB  - Autophagy is a conserved membrane-traffic pathway in eukaryotic cells that
      sequesters cytoplasmic components and delivers them to lysosomes. Recent research
      indicates that the degradation of undesirable or recyclable cytoplasmic
      components and organelles through autophagy plays a pivotal role as an
      intracellular surveillance system for recognition and eradication of pathogens
      that have invaded the cytoplasm. Many invasive bacteria, however, have highly
      evolved mechanisms to circumvent cellular autophagy. Indeed, recent reports
      describe intracellular pathogens as being capable of subverting or modifying
      autophagy activation and persisting within autophagosomes.

PMID- 16406775
TI  - Bordetella adenylate cyclase toxin: a swift saboteur of host defense.
AB  - Bordetella that infect mammals produce a multifunctional repeat in toxin (RTX)
      adenylate cyclase toxin known as CyaA, an excellent example of bacterial
      sophistication in subverting host defense. Recent reports show that interaction
      of CyaA with tracheal epithelial cells aids adhesion of Bordetella to ciliated
      mucosa and induces production of the pro-inflammatory cytokine interleukin, IL-6.
      Myeloid phagocytes, attracted to the site of infection are the target of freshly
      secreted CyaA that binds to the alpha(M)beta2 integrin (CD11b/CD18), penetrates
      cells and promptly suppresses their bactericidal functions by converting cellular
      ATP to cAMP. Such uncontrolled cAMP signaling can also drive CD11b-expressing
      immature dendritic cells into a semi-mature state, possibly hijacking them to
      shape the local adaptive immune response towards tolerance of the pathogen.

PMID- 16406776
TI  - Interactions between gastric epithelial stem cells and Helicobacter pylori in the
      setting of chronic atrophic gastritis.
AB  - Chronic atrophic gastritis (ChAG), a Helicobacter pylori-associated risk factor
      for the development of gastric cancer, involves loss of acid-producing parietal
      cells. Recent studies in gnotobiotic mouse models of ChAG have shown that
      parietal cell loss results in amplification of multi- and oligo-potential gastric
      stem cells that express sialylated glycan receptors recognized by H. pylori
      adhesins. Moreover, H. pylori resides within a subset of these stem cells.
      Studies of the transcriptomes of gastric stem cells, harvested directly from the
      stomachs of uninfected mice, using laser capture microdissection, suggest that
      they have the ability to complement some of the metabolic needs of H. pylori.
      These findings indicate that proliferating and non-proliferating gastric stem
      cells provide a habitat that could support H. pylori persistence in a gastric
      ecosystem that has lost its acid barrier to colonization by environmental, oral
      and intestinal microbes. One consequence to the host might be an increased risk
      of tumorigenesis.

PMID- 16406777
TI  - Uropathogenic Escherichia coli as a model of host-parasite interaction.
AB  - Resistance to mucosal infection varies greatly in the population, but the
      molecular basis of disease susceptibility is often unknown. Studies of host
      pathogen infections are helpful to identify virulence factors, which characterise
      disease isolates, and successful defence strategies of hosts that resist
      infection. In the urinary tract infection (UTI) model, we have identified crucial
      steps in the pathogen-activated innate host response, and studied the genetic
      control of these activation steps. Furthermore, genetic variation in the innate
      host-response defence is investigated as a basis of disease susceptibility. The
      Toll-like receptor 4 (TLR4) controls initial mucosal response to uropathogenic
      Escherichia coli (UPEC). Bacterial TLR4 activation in epithelial cells leads to
      chemokine secretion and neutrophil recruitment and TLR4 mutant mice develop an
      asymptomatic carrier state. The chemokine receptor CXCR1 determines the
      efficiency of neutrophil migration and activation, and thus of bacterial
      clearance. CXCR1 mutant mice become bacteremic and develop renal scars and
      studies in UTI prone children have detected low CXCR1 expression, suggesting that
      CXCR1 is also essential for human disease susceptibility.

PMID- 16406778
TI  - Salmonella type III secretion effectors: pulling the host cell's strings.
AB  - The enteric pathogen Salmonella employs type III secretion systems to transport a
      cocktail of effector proteins directly into its host cell. These effectors act in
      concert to control a variety of host cell processes to successfully invade
      intestinal cells and to establish an intracellular, replication-permissive niche.
      Recent studies reveal new insights into the molecular mechanisms that underlie
      effector protein injection, host cell invasion, and manipulation of vesicle
      trafficking induced by the interplay between multiple effectors and host systems.
      These findings corroborate the importance of spatio-temporal regulation of
      effector protein function for fine-tuned modulation of the host cell machinery.

PMID- 16406779
TI  - Ehrlichia subversion of host innate responses.
AB  - Anaplasma (formerly Ehrlichia) phagocytophilum and Ehrlichia chaffeensis, upon
      infection of humans, replicate in host leukocyte granulocytes and
      monocytes/macrophages, respectively. These unusual Gram-negative bacteria lack
      genes for biosynthesis of the lipopolysaccharide and peptidoglycan that activate
      host leukocytes. Caveolae-mediated endocytosis directs A. phagocytophilum and E.
      chaffeensis to an intracellular compartment secluded from oxygen-dependent and 
      independent killing. Furthermore, these bacteria orchestrate a remarkable series
      of events that culminate in suppression of NADPH oxidase, phagocyte activation
      and differentiation pathways, apoptosis, and interferon-gamma signaling in host
      leukocytes. They offer a fascinating example of how pathogens employ intricate
      strategies to usurp and subvert host cell function.

PMID- 16406780
TI  - Sticky connections: extracellular matrix protein recognition and integrin
      mediated cellular invasion by Staphylococcus aureus.
AB  - Staphylococcus aureus is a leading cause of hospital-acquired and often
      persistent infections. A key feature of pathogenic S. aureus is the expression of
      an array of extracellular matrix-binding proteins. In particular, the fibronectin
      binding proteins FnBP-A and FnBP-B afford the pathogen the ability to connect to
      cellular integrins and to trigger internalization into host cells. Recent work
      has highlighted the role of host cell invasion in the pathogenesis of S. aureus,
      the structure-function relationship of FnBPs, and the host factors required to
      allow bacterial uptake. Understanding the invasive capacity of S. aureus should
      open up new avenues to control this microorganism in diverse disease settings.

PMID- 16406781
TI  - Inhibition of jack bean urease by organobismuth compounds.
AB  - Inhibitory activity of organobismuth compounds, triarylbismuthanes 1 and their
      dihalides 2 and 3, was examined against jack bean urease. Besides triarylbismuth
      dichlorides 2, triarylbismuth difluorides 3 and bismuthanes 1 exhibited the
      activity. Of all these compounds, triphenylbismuth difluoride 3a and tris(4
      fluorophenyl)bismuth dichloride 2b showed the highest activity. These results
      indicate that generation of the inhibitory effect is not always governed by the
      Lewis acidity at the bismuth center. Such a tendency of inhibition by the
      organobismuth compounds is in good accord with that observed in the antibacterial
      activity against Helicobacter pylori, suggesting that H. pylori-produced urease
      may be a therapeutic target by bismuth-based drugs.

PMID- 16406782
TI  - Brequinar derivatives and species-specific drug design for dihydroorotate
      dehydrogenase.
AB  - Therapeutic agents brequinar sodium and leflunomide (Arava) work by binding in a
      hydrophobic tunnel formed by a highly variable N-terminus of family 2
      dihydroorotate dehydrogenase (DHODH). The X-ray crystallographic structure of an
      analog of brequinar bound to human DHODH was determined. In silico screening of a
      library of compounds suggested another subset of brequinar analogs that do not
      inhibit human DHODH as potentially effective inhibitors of Plasmodium falciparum
      DHODH.

PMID- 16406783
TI  - Protective effect of ferulic acid on gamma-radiation-induced micronuclei,
      dicentric aberration and lipid peroxidation in human lymphocytes.
AB  - In this study we examined radioprotective effect of ferulic acid (FA) on gamma
      radiation-induced dicentric aberration and lipid peroxidation with reference to
      alterations in cellular antioxidant status in cultured lymphocytes. To establish
      most effective protective support we used three different concentrations of FA
      (1, 5 and 10 microg/ml) and three different doses of gamma-radiation (1, 2 and 4
      Gy). Treatment of lymphocytes with FA alone (at 10 microg/ml) gave no significant
      change in micronuclei (MN), dicentric aberration (DC), thiobarbituric acid
      reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase
      (SOD), catalase (CAT) or glutathione peroxidase (GPx) activities when compared
      with normal lymphocytes; irradiation at 1, 2 and 4 Gy increased the MN and DC
      frequencies in a dose-dependent manner. Treatment with FA for 30 min before
      radiation exposure resulted in a significant decline of MN and DC yields as FA
      concentration increased. Compared to 1 Gy exposure alone, the extent to which FA
      (1 microg/ml) reduced the MN and DC yields was 75% and 50%, respectively. With 4
      Gy irradiation, FA (10 microg/ml) decreased 45% MN and 25% DC frequencies. FA
      pretreated lymphocytes (1, 5 and 10 microg/ml) showed progressively decreased
      TBARS levels after irradiation. Irradiation (1, 2 and 4 Gy) significantly
      decreased GSH levels, SOD, CAT and GPx activities in a dose-dependent manner.
      Pretreatment with 10 microg/ml of FA significantly (p<0.05) prevented the
      decreases in the radiation-induced GSH, SOD, CAT and GPx activities. These
      findings suggest potential use and benefit of FA as a radioprotector.

PMID- 16406784
TI  - Assessment of genotoxicity of 14 chemical agents used in dental practice: ability
      to induce chromosome aberrations in Syrian hamster embryo cells.
AB  - To assess the genotoxicity of 14 chemical agents used as locally applied agents
      in dental practice, the ability of these agents to elicit chromosome aberrations
      was examined using Syrian hamster embryo (SHE) cells. Chromosome aberrations in
      SHE cells were induced by treatment with three of eight chemical agents used as
      endodontic medicaments, i.e. ethylenediaminetetraacetic acid (EDTA), formocresol
      (a mixture of formalin and tricresol), and sodium arsenite. The other five
      chemical agents, i.e. chloramphenicol, p-chlorophenol, p-phenolsulfonic acid,
      sodium hypochlorite, and tetracycline hydrochloride exhibited a negative response
      for chromosome aberrations. Assessment of three dyes used for disclosing dental
      plaque showed chromosome aberrations induced by basic fuchsin but not by acid
      fuchsin and erythrosine B. Three local anesthetics, lidocaine hydrochloride,
      prilocaine hydrochloride, and procaine hydrochloride, were negative for
      chromosome aberrations. Among the ten chemical agents that exhibited a negative
      response in the assay, p-chlorophenol, sodium hypochlorite, and erythrosine B
      induced chromosome aberrations in SHE cells when treated in the presence of
      exogenous metabolic activation. The percentages of cells with polyploidy or
      endoreduplication were enhanced by formocresol, sodium arsenite, p-chlorophenol,
      p-phenolsulfonic acid, sodium hypochlorite, erythrosine B, prilocaine
      hydrochloride, and procaine hydrochloride in the absence or presence of exogenous
      metabolic activation. Our results indicate that the chemical agents that had a
      positive response in the present study are potentially genotoxic to mammalian
      cells.

PMID- 16406786
TI  - Spectral regression and correlation coefficients of some benzaldimines and
      salicylaldimines in different solvents.
AB  - Sixteen Schiff bases obtained from the condensation of benzaldehyde or
      salicylaldehyde with various amines (aniline, 4-carboxyaniline, phenylhydrazine,
      2,4-dinitrophenylhydrazine, ethylenediamine, hydrazine, o-phenylenediamine and
      2,6-pyridinediamine) are studied with UV-vis spectroscopy to observe the effect
      of solvents, substituents and other structural factors on the spectra. The bands
      involving different electronic transitions are interpreted. Computerized analysis
      and multiple regression techniques were applied to calculate the regression and
      correlation coefficients based on the equation that relates peak position
      lambda(max) to the solvent parameters that depend on the H-bonding ability,
      refractive index and dielectric constant of solvents.

PMID- 16406785
TI  - A comparative study examining the decision-making processes of medical and
      nursing staff in weaning patients from mechanical ventilation.
AB  - A prolonged period of mechanical ventilation is costly for both the patient, in
      terms of the risk of complications such as ventilator-acquired pneumonia, and to
      the health service due to the high cost of maintaining a patient in intensive
      care. The recognition of the role nurses can play in the weaning process and the
      desire to try and reduce weaning times led to the introduction of nurse-managed
      weaning on the intensive care unit which is the focus of this study. This means
      that both doctors and nurses are now responsible for making decisions about
      weaning. Flexible guidelines for weaning were devised which still require a large
      element of individual, clinical decision-making during the process. At every
      stage in the weaning process clinicians are required to make judgments about
      patient responses, using these judgments as the basis for their decision-making.
      This study examined the ways doctors and nurses make these decisions. Semi
      structured interviews were conducted with doctors and senior nurses. A grounded
      theory approach was used to analyse the results and the key themes of Treatment,
      Balance, Making Progress and The Individual were identified which were found to
      be linked with particular methods of decision-making.

PMID- 16406787
TI  - NMR study on cis-N-[4-[4-(1,2-benzisozole-3-yl)-1-piperazinyl] butyl]cyclohexane
      1,2-dicarboximide monohydrochloride dihydrate.
AB  - Cis-N-[4-[4-(1,2-benzisozole-3-yl)-1-piperazinyl]butyl]cyclohexane-1,2
      dicarboximide monohydrochloride dihydrate was studied spectroscopically. Complete
      NMR assignments were made using DEPT, H-H COSY, as well as HMQC and HMBC
      heteronuclear correlation techniques. The hydrochloride salt was found at delta >
      10. The dihydrate was present in the region delta 3-4 in DMSO-d6 solvent.
      Asymmetry carbon C3 brought chemical-shift-nonequivalent of cis-cyclohexanyl
      group, splitting four systems H1, H1', H2 and H2'. Diamagnetic anisotropy of
      benzisozolyl group results in three troops peaks of piperazinyl group.

PMID- 16406788
TI  - Structure and vibrations of Ga(n)N(n) (n = 3-10) clusters.
AB  - The structure and harmonic vibrations of Ga(n)N(n) (n = 3-10) clusters have been
      investigated using the B3LYP (Becke 3-parameter-Lee-Yang-Parr) density functional
      theory. All structures are found to be cumulenic D(nh) rings (equal bonds,
      alternating angles), with one intense out of plane mode and three infrared-active
      degenerate modes, of which the highest one is extremely intense and
      asymptotically increases to 1029 cm(-1) for n = 10. Comparisons with C2n,
      B(n)N(n), and Al(n)N(n) clusters, the structure and bonding type for the
      Ga(n)N(n) (n=3-10) clusters are consistent with those of the C2n (n = 3, 5, 7,
      ...) clusters, the B(n)N(n) (n = 3-10), and Al(n)N(n) (n = 3-9) clusters.

PMID- 16406789
TI  - 1H, 13C, NH, HH, CH COSY, HH NOESY NMR and UV-vis studies of Solophenyl red 3BL
      dye azo-hydrazone tautomerism in various solvents.
AB  - Azo-hydrazone tautomeric behavior of polyazo Solophenyl red 3BL (C.I. Direct 80)
      dye in different solvents (water, methanol and DMSO) was investigated using 1H,
      13C, NH, HH, CH COSY, HH NOESY NMR techniques and UV-vis spectroscopy. Two
      dimensional NMR experiments were used to assign 1H, 13C and 15N NMR lines
      unambiguously. Results showed that the hydrazone-form proton NMR signal appeared
      in the weakest field with respect to tetramethylsilane, in comparison with the
      amide and phenolic proton NMR signals. UV-vis absorption spectroscopic evidences
      showed that azo-hydrazone mixture exists in water and DMSO solvents, but in
      methanol, only azo tautomer was dominant, which was in a good agreement with NMR
      spectroscopic results.

PMID- 16406790
TI  - Metaproteomics: studying functional gene expression in microbial ecosystems.
AB  - The recent availability of extensive metagenomic sequences from various
      environmental microbial communities has extended the postgenomic era to the field
      of environmental microbiology. Although still restricted to a small number of
      studies, metaproteomic investigations have revealed interesting aspects of
      functional gene expression within microbial habitats that contain limited
      microbial diversity. These studies highlight the potential of proteomics for the
      study of microbial consortia. However, the application of proteomic
      investigations to complex microbial assemblages such as seawater and soil still
      presents considerable challenges. Nonetheless, metaproteomics will enhance the
      understanding of the microbial world and link microbial community composition to
      function.

PMID- 16406791
TI  - The roles of policy and professionalism in the protection of processed clinical
      data: a literature review.
AB  - BACKGROUND: Routinely collected clinical data is increasingly used for health
      service management, audit, and research. Even apparently anonymised data are
      subject to data protection. The relevant principles were set out in a treaty of
      the Council of Europe and subsequent policy has been based on these. However,
      little has been written about implementing policy and the role of health
      informaticians in this process. OBJECTIVE: To define the elements of an effective
      implementation policy; the role of the health informatician in protecting
      processed clinical data. METHODS: We performed a literature review of
      bibliographic databases, a manual search of the major medical informatics
      associations' websites, relevant working groups and an affiliated journal. Fifty
      four papers relevant to implementation were identified. RESULTS: The effective
      implementation of policy requires consideration of technical, organisational,
      personnel and professional issues. However, there is no clearly defined formula
      for successful implementation of data protection policy. CONCLUSIONS: Patients
      and professionals need a system they can trust, and processes that can be easily
      incorporated into everyday practice. The lack of a core generalisable theory or
      strong professional code in health informatics limits the ability of the health
      informaticians to implement policy.

PMID- 16406792
TI  - Synthesis and biological evaluation of new spin-labeled derivatives of
      podophyllotoxin.
AB  - In order to find compounds with superior bioactivity and less toxicity, a series
      of spin-labeled podophyllotoxin derivatives were synthesized and tested for the
      partition coefficients and cytotoxicity against P-388 and A-549. Furthermore, we
      also determined antioxidant activities of target molecular in tissues of SD rats
      by the TBA method. Results revealed that most synthesized compounds showed more
      significant cytotoxicity against P-388 and A-549 in vitro than VP-16. Among them,
      9d exhibited most potent cytotoxicity against P-388 and A-549 cells (IC50 is
      <0.01 and 0.13 microM, respectively). Also, the antioxidative activities showed
      that the modified compounds of 4'-demethylepipodophyllotoxin (9a-d and 10a-c) are
      higher than those of podophyllotoxin series (8a-d). The relationship between the
      cytotoxicity and antioxidative activity discussed.

PMID- 16406793
TI  - Differential expressions of aquaporin proteins in human cholestatic liver
      diseases.
AB  - Aquaporins (AQPs) are the channel forming membranous proteins involved in the
      biliary physiological homeostasis. Recently, we have reported the heterogeneous
      expression of AQPs in intrahepatic biliary epithelial cells or cholangiocytes in
      mice. However, the involvements of AQPs in hepatobiliary disorder are still
      unclear. Thus, we hypothesized that the AQP protein expressions are altered in
      human cholestatic disorders. METHODS: The AQP expressions of the immortalized
      human cholangiocytes cell line (H69) were assessed by immunoblotting. The
      expression of AQPs in liver biopsy specimens from various human cholestatic
      diseases as well as viral hepatitis were evaluated immunohistochemically. The
      degrees of staining were classified into four grades by comparison with staining
      intensity from controls. RESULTS: AQP1 expression, predominantly membranous, was
      confirmed by immunoblotting analysis. However, the other subtypes of AQP
      expression were not detected. In human pathological tissues, AQP1 expression by
      interlobular bile ducts was similar to normal and viral hepatitis, although this
      expression was attenuated according to bile duct injuries in PBC. On the
      contrary, the AQP1 expression by proliferating bile ductile (equivalent for small
      cholangiocytes) was enhanced. In intrahepatic cholestasis, AQP1 expressions were
      diminished, which was further associated with the aberrant expressions by
      periportal hepatocytes. CONCLUSIONS: AQP1 was expressed intensely in smaller
      proliferating bile ducts in human cholestatic liver disease. Also, the AQP1
      expression was decreased in injured duct cells undergoing degeneration in PBC.
      The AQP1 expression was decreased in intrahepatic cholestasis probably due to
      negative feed back of the decreased bile flow. The role of AQP expression
      profiles may help the understanding of the pathogenesis of human cholestatic
      liver diseases.

PMID- 16406794
TI  - Polyenylphosphatidylcholine pretreatment protects rat liver from
      ischemia/reperfusion injury.
AB  - BACKGROUND: Hepatic injury induced by ischemia/reperfusion following surgery,
      transplantation, or circulatory shock combined with resuscitation is a major
      clinical problem. Polyenylphosphatidylcholine (PPC) has strong antioxidant,
      cytoprotective and anti-inflammatory effects. AIM: In this study, the influence
      of PPC pretreatment on ischemia-reperfusion (I/R) injury of the liver was
      examined in rats. METHODS: The animals were divided into three groups: control
      (n=10), I/R (n=15) and I/R+PPC (n=15). PPC was given 100mg/day for 7 days before
      experiment. Several parameters of hepatic damage, oxidative stress, neutrophil
      infiltration and nuclear factor kappa beta (NF-kappaB) expression were measured
      as well as microscopic examination. RESULTS: We observed that a significant
      reduction in AST and ALT values in the PPC treated group when compared with the
      ischemic group. The increases in hepatic total NO(2)+NO(3) and MDA, and decreases
      in SOD and GSH levels after reperfusion were partially, but significantly,
      inhibited by PPC pretreatment. I/R induced increase in hepatic myeloperoxidase
      content and NF-kappaB expression were also lowered by PPC pretreatment. Animals
      pretreated with PPC presented minimal hemorrhage and reduced signs of liver
      injury. CONCLUSION: PPC pretretament provided significant protection againts I/R
      injury to the liver. This treatment could be therapeutic in liver transplantation
      and other conditions associated with I/R injury.

PMID- 16406795
TI  - No difference in expression of apoptosis-related proteins and apoptotic
      morphology in control, pathologically aged and Alzheimer's disease cases.
AB  - Apoptotic-like changes in the neocortex of control, pathologically aged and
      Alzheimer's disease (AD) cases were investigated. There was no increase in
      labeling or change in localization of labeling that distinguished between these
      cases for active caspase-3, -8, -9, Bax, Bcl-2 or TRADD. Bax, Bcl-2 and TRADD
      mRNA levels also differed little between case types, although there were small
      but significant decreases in Bax mRNA levels in AD compared to control cases and
      Bcl-2 mRNA in AD cases compared to pathologically aged and control cases. There
      was no difference in the percentage of apoptotic-like nuclei between these cases,
      except for a small but significant decrease in the inferior temporal gyrus of AD
      cases relative to controls. Nuclei observed within or adjacent to beta-amyloid
      plaques were rarely abnormal, and neurons bearing neurofibrillary tangles (NFTs)
      did not have abnormal nuclei. Apoptosis may not play a major role in the
      pathogenesis of neuronal degeneration of AD.

PMID- 16406796
TI  - Cytomegalovirus-encoded homologs of G protein-coupled receptors and chemokines.
AB  - BACKGROUND: Cytomegaloviruses (CMVs) have developed various sophisticated
      strategies to manipulate and evade the defense mechanisms of their hosts. Among
      the CMV genes that are predicted to be involved in these strategies are genes
      that encode mimics of cellular proteins, such as G protein-coupled receptors
      (GPCRs) and chemokines (CKs). These genes may have been pirated from the host
      genome during the long co-evolution of virus and host. OBJECTIVES: In this
      report, the putative functions of the CMV-encoded homologs of GPCRs and CKs in
      the pathogenesis of infection will be discussed. STUDY DESIGN: In order to
      present an overview of the current state of knowledge, the literature on the CMV
      encoded homologs of GPCRs and CKs was reviewed. RESULTS: The GPCR and CK homologs
      that are encoded by the CMVs represent immunomodulatory proteins with crucial
      roles in the pathogenesis of infection. CONCLUSIONS: In light of their function
      as well as accessibility on the cell surface, the CMV-encoded GPCR homologs are
      attractive targets for the development of new anti-viral therapies.

PMID- 16406797
TI  - Sensitivity of a modified version of the ARCHITECT Anti-HCV test in detecting
      samples with immunoblot-confirmed, low-level antibody to hepatitis C virus.
AB  - BACKGROUND AND OBJECTIVES: Compliance with current regulations regarding the
      prevention of hepatitis C virus (HCV) transmission in the blood transfusion
      setting requires the use of sensitive assays for HCV antibody (anti-HCV)
      detection, which should, ideally, identify any donor having had prior contact
      with the virus. Therefore, low-level anti-HCV positive blood units should be
      detected by the screening assays, even those reflecting a past and resolved
      infection. To assess the sensitivity of two versions of an automated
      chemiluminescent microparticle immunoassay (CMIA) for anti-HCV screening
      (ARCHITECT Anti-HCV), 113 single serum samples containing low levels of anti-HCV,
      assessed by two immunoblot tests, were selected from 3686 samples received for
      confirmation of HCV infection by a reference laboratory over a 2-year period.
      MATERIALS AND METHODS: The panel included 17 samples with HCV RNA detected by the
      polymerase chain reaction (PCR) and 96 PCR negative samples with either positive
      or indeterminate (anti-Core and anti-NS3 alone) results by immunoblot. RESULTS:
      All but 13 specimens (100/113, 88.5%) were detected by the current version of the
      ARCHITECT Anti-HCV assay and 10 additional samples (110/113, 97.3%) tested
      positive in a modified version of the test. CONCLUSION: The results showed that
      the modification introduced in the ARCHITECT Anti-HCV assay achieves a
      significant sensitivity improvement including samples with low-level anti-HCV
      which are either PCR positive or negative.

PMID- 16406798
TI  - Cytomegalovirus infection in solid organ transplant recipients: new challenges
      and their implications for preventive strategies.
AB  - BACKGROUND: Late-onset CMV disease is being increasingly recognized as a
      significant post-transplantation complication. OBJECTIVES: To discern the impact
      of antiviral prophylactic strategies on the emerging syndrome of late-onset CMV
      disease in organ transplant recipients. STUDY DESIGN: Review of existing reports
      and published data relevant to antiviral prophylaxis in organ transplant
      recipients. RESULTS: Prevention of CMV using prophylaxis has proven effective and
      is widely employed in organ transplant recipients. However, late-onset CMV
      disease is increasingly being recognized as a significant complication in these
      patients. The more potent the activity of the antiviral drug and the longer
      duration of prophylaxis, the greater likelihood of late-onset CMV disease. CMV
      seronegative recipients of seropositive donor allografts appear to be at a
      uniquely high risk. A higher proportion of patients with late-onset CMV have
      tissue invasive disease. Late-onset CMV disease in liver transplant recipients
      conferred an independently higher risk of mortality in the first post-transplant
      year. Prolonged antiviral therapy may impair the recovery of CMV-specific T-cell
      responses. Preemptive therapy appears to be less likely to be associated with CMV
      disease. CONCLUSIONS: Discernment of the pathophysiologic basis of late-onset CMV
      warrants investigation. Preemptive therapy may be the preferable approach to CMV
      prophylaxis.

PMID- 16406799
TI  - Emergence of a new human adenovirus type 4 (Ad4) genotype: identification of a
      novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates
      from US military recruits.
AB  - BACKGROUND: Ad4 is the principal etiological agent of acute respiratory disease
      (ARD) in the US military. Discovery of the novel 208bp inverted terminal repeated
      (ITR) sequence from a recent Ad4 Jax78 field isolate was totally distinct from
      the analogous 116bp ITR of Ad4 prototype. OBJECTIVES: To investigate the origin
      and distribution of the novel Ad4 ITR sequence from ARD infections. STUDY DESIGN:
      Direct sequencing of ligated Ad ITR termini. RESULTS: The new Ad4 ITR was highly
      homologous with the ITRs of human Ad subgroup B. The left post-ITR region of Ad4
      Jax78 was found to be highly homologous to the corresponding region of subgroup B
      Ads: 81% for Ad11 and 98% for Ad3 and Ad7. The right post-ITR region of Ad4 Jax78
      contained a truncated classic ITR of the Ad4 prototype. CONCLUSIONS: The Ad4
      Jax78 ITR most likely evolved from Ad4 prototype by substituting the Ad4
      prototype ITR with the subgroup B Ads ITR. The ITR-based PCR assays developed
      from this study can be used to distinguish the new Ad4 genotype from the
      classical Ad4 prototype. The new Ad4 genotype was first detected in 1976 from
      Georgia, USA, and is the main causative agent of ARD infections in US military
      population.

PMID- 16406800
TI  - Development and evaluation of a rapid IgM capture ELISA (JEV-Chex) for the
      diagnosis of Japanese encephalitis.
AB  - BACKGROUND: The IgM capture ELISA has been the most widely used diagnostic method
      for Japanese encephalitis. However, the lack of availability of validated
      commercial kits as well as the short shelf life of the kit reagents has limited
      the use of this technique to very few centres in Asia. OBJECTIVES: Development
      and evaluation of a rapid IgM capture ELISA (JEV Chex) in comparison to the
      conventional IgM capture ELISA. Produce key reagents such as cell culture derived
      JEV antigen and biotinylated monoclonal antibody which are stable at room
      temperature. STUDY DESIGN: The conventional IgM capture ELISA was modified to
      reduce the total assay time and two key reagents used in the assay JEV antigen
      and biotinylated anti-JEV monoclonal antibodies were rendered stable at room
      temperature using a special procedure. A multi-centric evaluation of this rapid
      ELISA was carried out using well characterized stored CSF and serum samples. Long
      term stability of the key reagents was also assessed over a period of 6 months.
      RESULTS: The rapid IgM capture ELISA developed by us showed complete concordance
      with the results obtained using the conventional ELISA at all the three centres
      where it was evaluated. In addition, the stability studies carried out with the
      inactivated cell culture antigen and the biotinylated monoclonal antibodies
      stored at room temperature for a period of 180 days revealed that both these
      reagents yielded consistent optical density values in the ELISA. CONCLUSIONS: The
      rapid ELISA format of the IgM capture ELISA (JEV-Chex) developed by us as well as
      the stability of reagents achieved by us in this study is what renders this rapid
      IgM capture ELISA very robust and user friendly since reagents can be stored at 4
      degrees C by peripheral labs.

PMID- 16406801
TI  - Component analysis of the fluorescence spectra of a lignin model compound.
AB  - In order to test whether lignin fluorescence originates from discrete
      fluorophores, fluorescence emission spectra of the lignin model dehydrogenative
      polymer (DHP) were analyzed by the band deconvolution method and time-resolved
      analysis of both the excitation and emission spectra. Two series of 22
      fluorescence emission spectra of DHP in chloroform/methanol (3:1, v/v) solution,
      and as a solid suspension in water, were deconvoluted into three fluorescence and
      one Raman Gaussian components. Emission spectra were obtained by stepwise
      variation of the excitation wavelength from 360 to 465 nm. Deconvolution was
      performed by nonlinear fitting of all three Gaussian parameters: area, width and
      position. Position of all components in a series was treated as a random variable
      and its approximate probability distribution (APD) calculated from a series of
      histograms with increasing number of abscissa intervals. A five peak multimodal
      APD profile was obtained for both series of DHP emission spectra. The mean
      fluorescence lifetime varied with wavelength both in the emission and the
      excitation decay-associated spectra (DAS), where four kinetic components were
      resolved. The shapes of the excitation spectra of the four components were quite
      different and gradually shifted bathochromically. The multicomponent nature of
      the DHP emission spectra along with the changes in the mean fluorescence lifetime
      and the form of the excitation DAS of the four components give evidence of the
      heterogeneous origin of fluorescent species emitting in the visible.

PMID- 16406802
TI  - Fluorescence spectroscopy combined with 5-aminolevulinic acid-induced
      protoporphyrin IX fluorescence in detecting oral premalignancy.
AB  - BACKGROUND: Early detection of premalignant/malignant lesions in the oral cavity
      can certainly improve the patient's prognosis. This study presents fluorescence
      imaging with the topical application of 5-aminolevulinic as a way to improve
      detection of various oral tissue pathologies. This procedure depends mainly on
      comparing the intensity of red and green fluorescence emitted from tissues during
      examination. MATERIALS AND METHODS: Seventy-one patients who presented with
      clinically suspicious oral leukoplakia were recruited for this study. Each of the
      patients was required to have 5-aminolevulinic acid in the form of mouth rinse
      prior to fluorescence imaging. Following this a surgical biopsy was acquired from
      the exact examination site. The results of the fluorescence spectroscopy have
      been compared with histopathology. RESULTS: A Student's t-test was applied to
      test the viability of the ratio between red and green fluorescence. The red-to
      green ratio was found to increase significantly when the lesion was identified as
      dysplastic or carcinoma in situ. By applying a threshold line to discriminate
      between normal and dysplastic lesions; a sensitivity of 83-90% and specificity of
      79-89% were obtained. CONCLUSION: Fluorescence spectroscopy combined with 5
      aminolevulinic acid-induced protoporphyrin IX was found as a valuable tool in the
      diagnosis of oral premalignancy. This technique offers the potential to be
      advantageous over other non-optical techniques in terms of providing real-time
      diagnosis, in situ monitoring, cost effectiveness and more tolerated by patient
      compared to surgical biopsy.

PMID- 16406804
TI  - CXCL8-induced FAK phosphorylation via CXCR1 and CXCR2: cytoskeleton- and integrin
      related mechanisms converge with FAK regulatory pathways in a receptor-specific
      manner.
AB  - CXCL8 is a potent chemokine, inducing focal adhesion kinase (FAK)
      phosphorylation, and migration via a FAK-mediated pathway. Since, unlike growth
      factors, chemokines directly control integrins and cytoskeleton rearrangements,
      we determined whether these elements regulate CXCL8-induced FAK phosphorylation.
      The analysis intentionally dissociated between the CXCL8 receptors CXCR1 and
      CXCR2. In both CXCR1- and CXCR2-expressing cells, actin and microtubules were
      required for CXCL8-induced FAK phosphorylation, and CXCL8-induced cell spreading
      was accompanied by concordant re-localization of FAK with actin and beta-tubulin.
      The phosphorylation of five FAK sites depended on intact actin filaments and
      microtubules. While in CXCR2-expressing cells FAK phosphorylation was adhesion
      dependent and was stimulated by fibronectin, in CXCR1-expressing cells FAK
      phosphorylation was adhesion-independent. Of note, even in the absence of
      integrin stimulation, the CXCL8-induced phosphorylation of FAK in CXCR1
      expressing cells required cytoskeletal elements. CXCL8-induced migration in both
      cell types was highly reliant on actin filaments, but only the migration of CXCR1
      expressing cells was fully dependent on microtubules. Overall, several aspects of
      CXCL8-induced FAK phosphorylation and migration are regulated in a receptor
      specific manner. These observations lay the basis for future investigation of the
      equilibrium between CXCR1 and CXCR2 in cells expressing both receptors together,
      such as neutrophils, endothelial cells and tumor cells.

PMID- 16406803
TI  - Characterization of heme environment and mechanism of peroxide bond cleavage in
      human prostacyclin synthase.
AB  - Prostacyclin is a potent mediator of vasodilation and anti-platelet aggregation.
      It is synthesized from prostaglandin H(2) by prostacyclin synthase (PGIS), a
      member of Family 8 in the cytochrome P450 superfamily. Unlike most P450s, which
      require exogenous reducing equivalents and an oxygen molecule for mono
      oxygenation, PGIS catalyzes an isomerization with an initial step of endoperoxide
      bond cleavage of prostaglandin H(2) (PGH(2)). The low abundance of PGIS in
      natural tissues necessitates heterologous expression for studies of
      structure/function relationships and reaction mechanism. We report here a high
      yield prokaryotic system for expression of enzymatically active human PGIS. The
      PGIS cDNA is modified by replacing the hydrophobic amino-terminal sequence with
      the more hydrophilic amino-terminal sequence from P450 2C5 and by adding a four
      histidine tag at the carboxyl terminus. The resulting recombinant PGIS associates
      with host cell membranes and was purified to electrophoretic homogeneity by
      nickel affinity, hydroxyapatite and CM Sepharose column chromatography. The
      recombinant PGIS, with a heme:protein ratio of 0.9:1, catalyzes prostacyclin
      formation at a K(m) of 13.3 muM PGH(2) and a V(max) of 980 per min. The
      dithionite-reduced PGIS binds CO with an on-rate of 5.6 x 10(5) M(-1) s(-1) and
      an off-rate of 15 s(-1). The ferrous-CO complex of PGIS is very short-lived and
      decays at a rate of 0.7 s(-1). Spectral binding assays showed that imidazole
      binds weakly to PGIS (K(d) approximately 0.5 mM,) but clotrimazole, a bulky and
      rigid imidazole derivative, binds strongly (K(d) approximately 1 microM). The
      transient nature of the CO complex and the weak imidazole binding seem to support
      an earlier proposal that PGIS active site has a limited space, but the tight
      binding of clotrimazole argues against this view. It appears that the heme distal
      pocket of PGIS is fairly adaptable to ligands of various structures. UV-visible
      absorption, magnetic circular dichroism and electron paramagnetic resonance
      spectra indicate that PGIS has a typical low-spin heme with a hydrophobic active
      site. PGIS catalyzes homolytic scission of the peroxide bond of a test substrate,
      10-hydroperoxyoctadeca-8,12-dienoic acid, accompanied by formation of a heme
      intermediate with a Compound II-like optical spectrum.

PMID- 16406805
TI  - Amelioration of adjuvant-induced arthritis by ursolic acid through altered
      Th1/Th2 cytokine production.
AB  - The objective of the study was to investigate the activity of ursolic acid (UA)
      on proinflammatory (Th1) and anti-inflammatory (Th2) cytokines in the peripheral
      blood of arthritic balb/c mice. Ursolic acid is ubiquitous in the plant kingdom
      and is a constituent of numerous plants which are having diversified phylogenetic
      origin and taxonomic position. We applied Cytometric bead array (CBA) technology
      for simultaneously measurement of these cytokines in adjuvant inflammatory
      arthritis induced mice treated with ursolic acid in graded oral doses. Cytometric
      bead array uses the sensitivity of amplified fluorescence detection by
      flowcytometer to measure soluble analytes in a particle based immune assay. This
      assay can accurately quantitate five cytokines in a 50 microl sample volume. The
      T-helper (Th1) deviated cells produce detectable level of tumor necrosis factor
      (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), while the Th2
      deviated cells produce significant amount of interleukin-4 (IL-4) and interleukin
      5 (IL-5). Oral administration of UA at doses of 10, 20, 40, 80 and 160 mg kg(-1)
      per oral dose inhibited the presence of IL-2, IFN-gamma and TNF-alpha in the
      peripheral blood.

PMID- 16406806
TI  - Renewing the T cell repertoire to arrest autoimmune aggression.
AB  - There is now evidence that high-dose immune ablation and autologous hematopoietic
      stem cell transplantation in humans triggers a reconstitution program that leads
      to the comprehensive renewal of the T cell repertoire. We argue here that several
      features of this program help to explain how autologous hematopoietic stem cell
      transplantation can induce long-term clinical remission from organ-specific-, as
      well as systemic, autoimmune diseases. We propose a model envisioning a
      coordinated sequence of events, rebuilding an immune system that is competent
      against infection but that is substantially reconfigured in a way that is less
      likely to redevelop autoimmunity.

PMID- 16406807
TI  - Monitoring the zinc affinity of the metallo-beta-lactamase CphA by automated
      nanoESI-MS.
AB  - Metallo-beta-lactamases are zinc containing enzymes that are able to hydrolyze
      and inactivate beta-lactam antibiotics. The subclass B2 enzyme CphA of Aeromonas
      hydrophila is a unique metallo-beta-lactamase because it degrades only
      carbapenems efficiently and is only active when it has one zinc ion bound. A zinc
      titration experiment was used to study the zinc affinity of the wild-type and of
      several mutant CphA enzymes. It shows that a second Zn(2+) is also bound at high
      ion concentrations. All samples were analyzed using mass spectrometry in
      combination with an automated nanoESI source. The metal-free enzyme has a bimodal
      charge distribution indicative of two conformational states. A completely folded
      enzyme is detected when the apo-enzyme has bound the first zinc. Intensity ratios
      of the different enzyme forms were used to deduce the zinc affinities. CphA
      enzymes mutated in metal ligands show decreased zinc affinity compared to wild
      type, especially D120 mutants.

PMID- 16406808
TI  - Ultra performance liquid chromatography (UPLC) further improves
      hydrogen/deuterium exchange mass spectrometry.
AB  - Ultra performance liquid chromatography (UPLC) employs particles smaller than 2
      microm in diameter to achieve superior resolution, speed, and sensitivity
      compared with high-performance liquid chromatography (HPLC). We have tested the
      suitability of UPLC for the analysis of deuterated peptides in hydrogen exchange
      mass spectrometry experiments. Superior resolution and sample throughput were
      obtained with UPLC versus HPLC. For highly deuterated model peptides, deuterium
      loss using UPLC was greater than the deuterium loss observed using a conventional
      HPLC system, primarily as a result of the injection requirements of the UPLC
      system. Partially deuterated cytochrome c peptides also lost more deuterium in
      UPLC versus HPLC, although the effect was not as pronounced as it was for the
      highly deuterated model peptides. The exceptional chromatographic aspects of UPLC
      make it a very attractive alternative to HPLC for hydrogen exchange mass
      spectrometry experiments.

PMID- 16406809
TI  - Using molecular recognition of beta-cyclodextrin to determine molecular weights
      of low-molecular-weight explosives by MALDI-TOF mass spectrometry.
AB  - This study presents a novel method for determining the molecular weights of low
      molecular weight (MW) energetic compounds through their complexes of beta
      cyclodextrin (beta-CD) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) in a mass range of 500 to 1700 Da,
      avoiding matrix interference. The MWs of one composite explosive composed of 2,6
      DNT, TNT, and RDX, one propellant with unknown components, and 14 single-compound
      explosives (RDX, HMX, 3,4-DNT, 2,6-DNT, 2,5-DNT, 2,4,6-TNT, TNAZ, DNI, BTTN, NG,
      TO, NTO, NP, and 662) were measured. The molecular recognition and inclusion
      behavior of beta-CD to energetic materials (EMs) were investigated. The results
      show that (1) the established method is sensitive, simple, accurate, and suitable
      for determining the MWs of low-MW single-compound explosives and energetic
      components in composite explosives and propellants; and (2) beta-CD has good
      inclusion and modular recognition abilities to the above EMs.

PMID- 16406810
TI  - Proteomics of bovine myelin sheath: characterization of a truncated form of P0 by
      MALDI-TOF/TOF mass spectrometry.
AB  - The glycoprotein P0, the major structural protein of the peripheral nerve myelin,
      plays a critical role in holding myelin lamellae together via interaction of both
      extracellular and cytoplasmic domains. Mutations in the human P0 gene give rise
      to severe and progressive forms of dominantly inherited peripheral neuropathies
      like CMT1B. Here we report on the characterization of a bovine P0-derived protein
      of nearly 26 kD that corresponds to the P0 protein truncated in its cytoplasmic
      domain. Matrix assisted laser desorption ionization (MALDI)-time-of-flight/time
      of-flight (TOF/TOF) mass spectrometry (MS) analysis on its tryptic digest has
      provided a peptide mapping, the main difference of which from the normal P0
      analog was represented by the absence of the cluster of peaks at m/z 1513.7501,
      1530.7701, and 1546.7651. The latter corresponds to the P0 fragment QTPVLYAMLDHSR
      and to its pyroglutamic and methionine-oxidized derivatives. The species at
      1530.7701 covering the sequence 186-198 of P0 is not an artifact and might have a
      functional role in the myelin architecture.

PMID- 16406812
TI  - MasterCARD: a priceless link to innate immunity.
AB  - Intracellular viral infection is detected by the cytoplasmic RNA helicase RIG-I,
      which has an essential role in initiating the host antiviral response. The
      adaptor molecule that connects RIG-I sensing of incoming viral RNA to downstream
      signaling and gene activation has recently been elucidated by four independent
      research groups, and has been ascribed four different names: MAVS, IPS-1, VISA
      and Cardif. The fact that MAVS/IPS-1/VISA/Cardif localizes to the mitochondrial
      membrane suggests a link between viral infection, mitochondrial function and
      development of innate immunity. Furthermore, the hepatitis C virus NS3/4A
      protease specifically cleaves MAVS/IPS-1/VISA/Cardif as part of its immune
      evasion strategy. These studies highlight a novel role for the mitochondria and
      for caspase activation and recruitment domain (CARD)-containing proteins in
      coordinating immune and apoptotic responses.

PMID- 16406813
TI  - Effect of urban traffic, individual habits, and genetic polymorphisms on
      background urinary 1-hydroxypyrene excretion.
AB  - PURPOSE: Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs)
      and genetic polymorphisms were investigated in relation to their contribution to
      interindividual variation in baseline levels of urinary 1-hydroxypyrene (1-OHP)
      excretion in subjects without occupational exposure to PAHs. METHODS: Urinary
      excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men.
      Questionnaire information was collected on possible environmental and individual
      sources of PAH exposure. A subset of 70 individuals also was evaluated for a
      single-nucleotide polymorphism (Ex7+295C-->T) in the cytochrome P-450 1A2
      (CYP1A2) gene, and 61 of these also were evaluated for the glutathione
      transferase T1 (GSTT1) gene polymorphism. RESULTS: 1-OHP values did not show a
      significant seasonal variability and were unaffected by age; education; body mass
      index; smoking status, including passive smoking; or the C-->T base substitution
      in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with
      logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9;
      95% confidence interval, 1.0-24.9), and frequent intake of grilled meat (odds
      ratio, 6.9; 95% confidence interval, 1.1-43.5) were significant predictors of
      background urinary 1-OHP levels of 0.50 microg/g creatinine or greater. Elevated
      risks also were associated with daily alcohol intake greater than 65 g and the
      nonnull GSTT1 genotype. CONCLUSION: Our study shows that exposure to urban
      traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to
      interindividual variation in background levels of 1-OHP urinary excretion in
      subjects without occupational exposure to PAHs.

PMID- 16406814
TI  - Consumption of antioxidant-rich beverages and risk for breast cancer in French
      women.
AB  - PURPOSE: The objective of the study is to evaluate the relation between
      antioxidant-rich beverages and the incidence of breast cancer. METHODS: This
      prospective study consisted of 4396 women without a history of cancer who were
      participants in the French Supplementation en Vitamines et Mineraux Antioxydants
      Study. Beverage consumption was estimated by using three nonconsecutive 24-hour
      recalls. Incident cancer cases were identified through clinical examinations
      performed every other year, including, e.g., a screening mammogram, and through a
      monthly health questionnaire. RESULTS: During the median 6.6 years of follow-up,
      95 breast cancers were diagnosed. In a multivariate model, an inverse association
      between herbal tea consumption and risk for breast cancer was observed (compared
      with nondrinkers, drinking 1 to 149 mL/d; relative risk [RR], 0.93; 95%
      confidence interval [CI], 0.48-1.80, and for > or =150 mL/d; RR, 0.43; 95% CI,
      0.20-0.94; p for trend = 0.04). Consumption of coffee, tea, fruit juices, or wine
      was not associated with risk for breast cancer. CONCLUSION: Results of this study
      suggest that consumption of herbal tea may have a role in the prevention of
      breast cancer.

PMID- 16406815
TI  - Modelling variations in corallite morphology of Galaxea fascicularis coral
      colonies with depth and light on coastal fringing reefs in the Wakatobi Marine
      National Park (S.E. Sulawesi, Indonesia).
AB  - Coastal environments in the tropics can suffer from high sedimentation and low
      light levels. Galaxea fascicularis is a hermatypic coral that is relatively
      resilient to stress from bleaching and from sedimentation. Corallite dimensions-
      width, height, corallite densities and inter-corallite distances--of Galaxea
      fascicularis colonies varied significantly with depth, and so with incident light
      at the Sampela reef in the Wakatobi Marine National Park, S.E. Sulawesi,
      Indonesia. Modelling studies based on our data showed that corallite width
      decreased with the amount of incident light, while corallite height increased
      with the amount of incident light (r2 values of 0.835 for width and 0.869 for
      height). In all colonies, inter-corallite distance decreased significantly with
      the amount of incident light (r2 = 0.89). Colony width/height ratio increased in
      a linear fashion with inter-corallite distance for all colonies studied (r2 =
      0.65). Current flow as judged using tags did not appear to be a factor in
      variations of corallite dimensions. Our results suggest that under low light
      conditions, distribution and size of corallites may optimise heterotrophic
      nutrition, while in conditions where light is not limiting, distribution and size
      of corallites may be optimal for photosynthesis.

PMID- 16406816
TI  - The creation of a brain atlas for image guided neurosurgery using serial
      histological data.
AB  - Digital and print brain atlases have been used with success to help in the
      planning of neurosurgical interventions. In this paper, a technique presented for
      the creation of a brain atlas of the basal ganglia and the thalamus derived from
      serial histological data. Photographs of coronal histological sections were
      digitized and anatomical structures were manually segmented. A slice-to-slice
      nonlinear registration technique was used to correct for spatial distortions
      introduced into the histological data set at the time of acquisition. Since the
      histological data were acquired without any anatomical reference (e.g., block
      face imaging, post-mortem MRI), this registration technique was optimized to use
      an error metric which calculates a nonlinear transformation minimizing the mean
      distance between the segmented contours between adjacent pairs of slices in the
      data set. A voxel-by-voxel intensity correction field was also estimated for each
      slice to correct for lighting and staining inhomogeneity. The reconstructed three
      dimensional (3D) histological volume can be viewed in transverse and sagittal
      directions in addition to the original coronal. Nonlinear transformations used to
      correct for spatial distortions of the histological data were applied to the
      segmented structure contours. These contours were then tessellated to create
      three-dimensional geometric objects representing the different anatomic regions
      in register with the histological volumes. This yields two alternate
      representations (one histological and one geometric) of the atlas. To register
      the atlas to a standard reference MR volume created from the average of 27 T1
      weighted MR volumes, a pseudo-MRI was created by setting the intensity of each
      anatomical region defined in the geometric atlas to match the intensity of the
      corresponding region of the reference MR volume. This allowed the estimation of a
      3D nonlinear transformation using a correlation based registration scheme to fit
      the atlas to the reference MRI. The result of this procedure is a contiguous 3D
      histological volume, a set of 3D objects defining the basal ganglia and thalamus,
      both of which are registered to a standard MRI data set, for use for
      neurosurgical planning.

PMID- 16406817
TI  - Recent developments in oximetry and perfusion-based mapping techniques and their
      role in the surgical treatment of neocortical epilepsy.
AB  - Detailed understanding of neurovascular coupling during epilepsy is critical for
      the interpretation of various perfusion-based imaging techniques, such as
      positron emission tomography, single-photon-emission computed tomography, and
      functional magnetic resonance imaging, which are used to guide surgical therapy.
      We used high-resolution intrinsic signal- and voltage-sensitive dye imaging, as
      well as oxygen-sensitive electrodes, to map the precise spatiotemporal
      relationship between excitatory and inhibitory neuronal activity, cerebral blood
      volume, and oximetry during epilepsy. We observed a rapid focal decrease in
      tissue oxygenation and an increase in deoxygenated hemoglobin in association with
      both interictal and ictal events. This "epileptic dip" in oxygenation lasts
      several seconds following both interictal and ictal events, implying that for a
      period, cerebral blood flow is inadequate to meet metabolic demand. We also
      observed a rapid focal increase in cerebral blood volume that soon spread to
      adjacent nonepileptic gyri. Likewise, a diffuse decrease in deoxygenated
      hemoglobin, related to the blood oxygen level-dependent signal recorded with
      functional magnetic resonance imaging, spread to adjacent gyri and was poorly
      localized.

PMID- 16406818
TI  - Teachers' knowledge about epilepsy and attitudes toward students with epilepsy:
      results of a national survey.
AB  - The attitudes and epilepsy-related knowledge of teachers are an important
      component of the educational experiences of children with epilepsy. Unfortunately
      however, the exploration of teacher attitudes and knowledge has been extremely
      limited in the United States. This article describes a survey-based research
      study of the attitudes and epilepsy-related knowledge of a randomly selected
      national sample of 512 elementary and middle school teachers in the United
      States. The questionnaire included the Scale of Attitudes Toward Persons with
      Epilepsy (ATPE), a summated rating scale that measures both attitudes toward
      persons with epilepsy and knowledge about epilepsy, as well as a demographic and
      teaching experience survey and several additional attitude and knowledge items
      developed by the researchers. The results suggest that although teachers'
      attitudes about epilepsy were generally positive, there were significant deficits
      in terms of general knowledge about epilepsy, its impact in educational settings,
      and the appropriate management of epilepsy and seizures in the classroom.
      Critical areas in which to focus remedial education and outreach efforts are
      identified.

PMID- 16406820
TI  - The systematic position of Cladodiopsis Seguy, 1949 and the origin of sexual
      dimorphism in stalk-eyed flies (Diptera: Diopsidae) inferred from DNA sequence
      data.

PMID- 16406819
TI  - Probing the relationships of the branchiopod crustaceans.
AB  - The Branchiopoda display extraordinary variation in body form, even within the
      morphologically diverse crustaceans. To fully understand the origin and evolution
      of these morphological reconfigurations, a robust phylogeny of the group is
      essential. To infer the affinities among branchiopods, we employed two approaches
      to taxon and gene sampling, presented new sequence data from three genes,
      incorporated previously published sequence data from three additional genes, and
      utilized comprehensive techniques of phylogeny reconstruction. The results
      provided support for a number of longstanding hypotheses concerning the
      relationships among the orders. For example, we obtained support for the
      Cladoceromorpha and Gymnomera, and favoured a unique arrangement of the
      cladoceran orders. A few affinities remain to be resolved, particularly at the
      base of the Phyllopoda and within the Anomopoda. However, the results suggest
      that increased gene sampling is recommended for future investigations of
      branchiopod systematics.

PMID- 16406821
TI  - The xenoestrogen 4-nonylphenol modulates hepatic gene expression of pregnane X
      receptor, aryl hydrocarbon receptor, CYP3A and CYP1A1 in juvenile Atlantic salmon
      (Salmo salar).
AB  - Nonylphenol is a degradation product of alkylphenol polyethoxylates (APEs). APEs
      represent an important class of non-ionic surfactants widely used in many
      detergent formulations and plastic products for industrial and domestic use.
      Nonylphenol interacts with xenobiotic- and drug-metabolizing CYP forms, including
      members of the CYP3A and CYP1A1 subfamilies in fish. The pregnane X receptor
      (PXR) and aryl hydrocarbon receptor (AhR) are known regulators of the induction
      of CYP3A and CYP1A1, respectively. Previously in our laboratory, we have shown
      that nonylphenol, in addition to inducing plasma egg-yolk and eggshell proteins,
      also modulates hepatic CYP3A- and CYP1A1-mediated enzyme activities in juvenile
      Atlantic salmon. Given the potential for indirect actions of nonylphenol on
      xenobiotic and steroid metabolism, studies were carried out to determine the
      effects of nonylphenol on the expression of two critical enzyme systems using
      juvenile salmon and waterborne nonylphenol at environmentally relevant
      concentrations (5, 15 and 50 microg/L) and ethanol solvent control and sampled at
      different time intervals (days 0 (control), 3 and 7) post-exposure. Our data show
      that nonylphenol-induced CYP3A and CYP1A1 mRNA levels correlate with PXR and AhR
      at day 7 post-exposure to 5 and 15 microg NP/L. For CYP1A1 and AhR, nonylphenol
      caused a temporal decrease at day 3 post-exposure, thereafter CYP1A1 and AhR mRNA
      levels were significantly induced at day 7. 50 microg NP/L caused a more
      pronounced effect on CYP1A1 by decreasing the mRNA levels at days 3 and 7,
      compared to control. Despite the decreased CYP1A1 mRNA levels at day 7, 50 microg
      NP/L caused a significant induction of AhR mRNA at the same time period. This
      study suggests a possible regulation by xenoestrogens of fish hepatic CYP3A and
      CYP1A1 enzymes via PXR and AhR, respectively, and may have impact on the
      metabolism of endogenous and exogenous substrates. This is the first study that
      simultaneously examined CYP3A, CYP1A1, PXR and AhR transcripts following
      nonylphenol treatment in any aquatic species or earlier diverging vertebrates.

PMID- 16406822
TI  - Role of C-terminus of Kir7.1 potassium channel in cell-surface expression.
AB  - Inward rectifier K+ channel Kir7.1 is predominantly expressed on the plasma
      membrane of a variety of ion-transporting epithelia. The electrophysiological
      property of Kir7.1 has been well characterized but the mechanism underlying the
      plasma-membrane targeting remains elusive. To address this issue, we examined the
      effect of deletion and site-directed mutagenesis on the plasma-membrane
      localization of Kir7.1 in Madin-Darby canine kidney cells by immunofluorescence
      microscopy and cell-surface biotinylation. Although deletions of up to 37 amino
      acid residues from the C-terminus had no effect, further deletion resulted in
      accumulation of the mutant proteins in intracellular membranes. No sequence motif
      for subcellular targeting was found in the distal C-terminal region. The cell
      surface expression of the deletion mutant lacking 38 or 40 C-terminal residues
      was restored by addition of one or three alanine residues, respectively, to the C
      terminus end. These results suggest that the C-terminal length plays an important
      role in the plasma-membrane localization of Kir7.1.

PMID- 16406823
TI  - A computer simulation analysis of the accuracy of partial genome sequencing and
      restriction fragment analysis in the reconstruction of phylogenetic
      relationships.
AB  - Partial genome sequencing (PGS) and restriction fragment analysis (RFA) are used
      frequently in molecular epidemiologic investigations. The relative accuracy of
      PGS and RFA in phylogenetic reconstruction has not been assessed. In this study,
      32 model phylogenetic trees with 16 extant lineages were generated, for which DNA
      sequences were simulated under varying conditions of genome length, nucleotide
      substitution rate, and between-site substitution rate variation. Genotyping using
      PGS and RFA was simulated. The effect of tree structure (stemminess, imbalance,
      lineage variation) on the accuracy of phylogenetic reconstruction (topological
      and branch length similarity) was evaluated. Overall, PGS was more accurate than
      RFA. The accuracy of PGS increased with increasing sequence length. The accuracy
      of RFA increased with the number of restriction enzymes used. In fragment size
      comparison, the Dice and Nei-Li algorithms differed little, with both more
      accurate than the Fragment Size Distribution algorithm. For RFA, higher tree
      stemminess and longer genome length were associated with higher topological
      accuracy, whereas lower tree stemminess and lower substitution rates were
      associated with higher branch length accuracy. For PGS, lower tree imbalance was
      associated with higher topological accuracy, whereas lower tree stemminess,
      higher substitution rate, and lower between-site substitution rate variation were
      associated with higher branch length accuracy. RFA had higher topological
      accuracy than PGS only for the shortest sequence length (200 bps) at a low
      substitution rate, high tree stemminess, and long genome length. PGS had equal or
      higher accuracy in branch length reconstruction than RFA under all conditions
      investigated. Thus, partial genome sequencing is recommended over restriction
      fragment analysis for conditions within the parameter space examined.

PMID- 16406824
TI  - Intestinal adaptation to diet in the young domestic and wild turkey (Meleagris
      gallopavo).
AB  - The short-term effects of diet on jejunal growth, alanine transport rate, and
      leucine aminopeptidase activity (LAP) were compared in the domestic and wild
      turkey poult. One-day-old poults of each strain were fed diets of high vs., low
      protein, with carbohydrate varied to maintain isocaloric conditions. Prior to
      feeding, relative jejunal mass and alanine transport rates were not significantly
      different in the two turkey strains, whereas LAP activity was 270% higher in wild
      poults. After feeding for 72 h, relative jejunal mass doubled in both turkey
      strains. In domestic turkeys, alanine transport rate and LAP activity were
      reduced by approximately 42% and 25%, respectively, in poults fed a 24% protein
      69% carbohydrate diet vs. a 49% protein-35% carbohydrate diet. Analysis of the
      combined data from feeding experiments revealed that alanine transport rate was
      not correlated with total food, protein or lipid intake, but was negatively
      correlated with carbohydrate consumption (P<0.05). In wild turkeys, neither
      alanine transport rate nor LAP activity were altered by diet. These results
      reveal that domestic turkey hatchlings can modulate protein digestive and
      absorptive functions as protein/carbohydrate composition of the diet changes and
      suggest that high dietary carbohydrate down-regulates the intestinal alanine
      transporter.

PMID- 16406825
TI  - Feedback regulation of growth hormone synthesis and secretion in fish and the
      emerging concept of intrapituitary feedback loop.
AB  - Growth hormone (GH) is known to play a key role in the regulation of body growth
      and metabolism. Similar to mammals, GH secretion in fish is under the control of
      hypothalamic factors. Besides, signals generated within the pituitary and/or from
      peripheral tissues/organs can also exert a feedback control on GH release by
      effects acting on both the hypothalamus and/or anterior pituitary. Among these
      feedback signals, the functional role of IGF is well conserved from fish to
      mammals. In contrast, the effects of steroids and thyroid hormones are more
      variable and appear to be species-specific. Recently, a novel intrapituitary
      feedback loop regulating GH release and GH gene expression has been identified in
      fish. This feedback loop has three functional components: (i) LH induction of GH
      release from somatotrophs, (ii) amplification of GH secretion by GH
      autoregulation in somatotrophs, and (iii) GH feedback inhibition of LH release
      from neighboring gonadotrophs. In this article, the mechanisms for feedback
      control of GH synthesis and secretion are reviewed and functional implications of
      this local feedback loop are discussed. This intrapituitary feedback loop may
      represent a new facet of pituitary research with potential applications in
      aquaculture and clinical studies.

PMID- 16406826
TI  - Purification and kinetics of sheep kidney cortex glucose-6-phosphate
      dehydrogenase.
AB  - Glucose-6-phosphate dehydrogenase (G-6-PD) is one of the important enzymes, which
      is responsible for the production of NADPH and ribose-5-phosphate. NADPH is used
      for the biosynthetic reactions and protection of the cells from free radicals. We
      have investigated some properties and kinetic mechanism of the sheep kidney
      cortex G-6-PD. This enzyme has been purified 1,384-fold with a yield of 16.96%
      and had a specific activity of 27.69 U/mg protein. The purification procedure
      consists of 2', 5'-ADP-Sepharose 4B affinity chromatography after
      ultracentrifugation. The sheep kidney cortex G-6-PD was found to operate
      according to a Ping Pong Bi Bi mechanism. The kinetic parameters from sheep K(m)
      values for G-6-P and NADP(+) and V(m) were determined to be 0.041+/-0.0043 mM,
      0.0147+/-0.001 mM and 28.23+/-0.86 microMol min(-1) mg protein(-1), respectively.
      The pH optimum was 7.4 and the optimum temperature was 45 degrees C. In our
      previous study we have found that lamb kidney cortex G-6-PD enzyme obeys 'Ordered
      Bi Bi' mechanism. We suggest that kinetic mechanism altered due to the aging
      since sheep G-6-PD uses a 'ping pong' mechanism.

PMID- 16406827
TI  - The utilization of lipovitellin during blue crab (Callinectes sapidus)
      embryogenesis.
AB  - Embryos of the blue crab Callinectes sapidus develop in egg sacs carried on the
      abdomen of the female. They develop over a period of 10-13 days at 28 degrees C
      and are nutritionally dependent on yolk until they emerge from the egg sacs as
      free-swimming zoeae. The principal component of blue crab yolk is lipovitellin
      (LpII), a water-soluble lipoprotein composed of approximately equal amounts of
      lipid and protein. We followed changes in the concentration of apoproteins of
      LpII during embryogenesis by ELISA and Western blots, using monoclonal antibodies
      against two LpII apoprotein associated peptides identified as Protein A (107 kDa)
      and Protein B (75 kDa). During embryogenesis there was a decrease in Protein B
      but an increase in two smaller peptides (52 and 35 kDa) that reacted with the
      Protein B antibody. Utilization of LpII during embryogenesis was also followed
      morphologically by immunohistochemistry. Utilization of LpII was slow in early
      embryonic stages, followed by rapid utilization in late embryonic stages, such
      that only traces of LpII were present at the end of embryogenesis. The cells of
      the developing hepatopancreas appear to play an important role in the utilization
      of LpII.

PMID- 16406828
TI  - Mitochondrial dysfunction in NASH: causes, consequences and possible means to
      prevent it.
AB  - Calorie-enriched diet and lack of exercise are causing a worldwide surge of
      obesity, insulin resistance and lipid accretion in liver (i.e. hepatic
      steatosis), which can lead to steatohepatitis. Steatosis and nonalcoholic
      steatohepatitis (NASH) can also be induced by drugs such as amiodarone, tamoxifen
      and some antiretroviral drugs, including stavudine and zidovudine. There is
      accumulating evidence that mitochondrial dysfunction (more particularly
      respiratory chain deficiency) plays a key role in the physiopathology of NASH
      whatever its initial cause. In contrast, the mitochondrial beta-oxidation of
      fatty acids can be either increased (as in insulin resistance-associated NASH) or
      decreased (as in drug-induced NASH). However, in both circumstances, generation
      of reactive oxygen species (ROS) by the damaged respiratory chain can be
      augmented. ROS generation in an environment enriched in lipids in turn induces
      lipid peroxidation which releases highly reactive aldehydic derivatives (e.g.
      malondialdehyde) that have diverse detrimental effects on hepatocytes and other
      hepatic cells. In hepatocytes, ROS, reactive nitrogen species and lipid
      peroxidation products further impair the respiratory chain, either directly or
      indirectly through oxidative damage to the mitochondrial genome. This
      consequently leads to the generation of more ROS and a vicious cycle occurs.
      Mitochondrial dysfunction can also lead to apoptosis or necrosis depending on the
      energy status of the cell. ROS and lipid peroxidation products also increase the
      generation of several cytokines (TNF-alpha, TGF-beta, Fas ligand) playing a key
      role in cell death, inflammation and fibrosis. Recent investigations have shown
      that some genetic polymorphisms can significantly increase the risk of
      steatohepatitis and that several drugs can prevent or even reverse NASH.
      Interestingly, most of these drugs could exert their beneficial effects by
      improving directly or indirectly mitochondrial function in liver. Finding a drug,
      which could fully prevent oxidative stress and mitochondrial dysfunction in NASH
      is a major challenge for the next decade.

PMID- 16406829
TI  - Isolated spinal intramedullary tuberculoma in a healthy immunocompetent adult.

PMID- 16406830
TI  - Does central nitric oxide elicit pulmonary hypertension in conscious rats?
AB  - The mechanisms involved in the pathogenesis of pulmonary arterial hypertension
      (PAH) remain unclear. Nitric oxide (NO) centrally attenuates sympathetic outflow
      and, therefore, may chronically modulate pulmonary arterial pressure (PAP),
      especially during the development of chronic hypoxia-induced PAH. To test this
      hypothesis, 20 male Sprague-Dawley rats (B.W. approximately 200-320 g) were
      chronically implanted with a telemetric transmitter for the continuous
      measurement of PAP, and an osmotic pump for intracerebroventricular (i.c.v.)
      administration of either aCSF (control), L-NAME (150 microg/kg/day) or the NO
      donor, SIN-1 (100 microg/kg/day). Rats spent 7 days in normoxia, and then 14 days
      in hypoxia (CH=12% O2). In normoxia, exogenous NO elevated PAP by approximately
      64%, although this increase in PAP could be prevented by isoproterenol (200
      mug/kg). PAH occurred in all rats following 14 days of hypoxia. L-NAME did not
      alter baseline MPAP or the physiological responses to hypoxia. Our results
      suggest that central NO increases MPAP, although the mechanisms involved remain
      to be fully elucidated.

PMID- 16406831
TI  - Direct sonication of acetic acid in aqueous solutions.
AB  - Sonochemical oxidation has a promising future in the area of waste water
      treatment as one of the advanced oxidation methods. In this study, direct
      ultrasonic degradation of acetic acid was investigated in low powers (0.1-0.4 W)
      and in a frequency range of 30-100 kHz. An ultrasonic transducer was used for
      sonication. The results showed that there was an optimum frequency at 60 kHz for
      direct sonication of acetic acid and degradation rate increased up to a power of
      0.2 W and then it decreased. Sonochemistry is associated with the bubble of
      cavitation which depends on the sound pressure field and nature of molecule.
      Therefore, the frequency and intensity have to be optimized for the minimization
      of energy requirement during waste water treatment with ultrasound.

PMID- 16406832
TI  - Simultaneous determination of 16 anti-HIV drugs in human plasma by high
      performance liquid chromatography.
AB  - Therapeutic drug monitoring (TDM) is pivotal to improve the management of HIV
      infection. Here, a HPLC-UV method has been developed to quantify simultaneously
      seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir,
      nelfinavir, ritonavir, and saquinavir; PIs), seven nucleoside reverse
      transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine,
      stavudine, zalcitabine, and zidovudine; NRTIs), and two non-nucleoside reverse
      transcriptase inhibitors (efavirenz and nevirapine; NNRTIs) in human plasma. The
      volume of the plasma sample was 600 microL. This method involved automated solid
      phase extraction with Oasis HLB Cartridge 1 cc (divinylbenzene and N
      vinylpyrrolidone) and evaporation in a water bath under nitrogen stream. The
      extracted samples were reconstituted with 100 microL methanol. Twenty microliters
      of these samples were injected into a HPLC-UV system, the analytes were eluted on
      an analytical C(18) Symmetry column (250 mm x 4.6mm I.D.) with a particle size of
      5 microm. The mobile phase (0.01 M KH(2)PO(4) and acetonitrile) was delivered at
      1.0 mL/min with linear gradient elution. The total run time for a single analysis
      was 35 min, the anti-HIV drugs were detected by UV at 240 and 260 nm. The
      calibration curves were linear up to 10 microg/mL. The absolute recovery ranged
      between 88 and 120%. The in vitro stability of anti-HIV drugs (0.005-10
      microg/mL) in plasma has been studied at 24.0 degrees C. On these bases, a two to
      four analyte method has been tailored to the individual needs of the HIV-infected
      patient. The HPLC-UV method here reported has been validated and is currently
      applied to monitor PIs, NRTIs, and NNRTIs in plasma of HIV-infected patients. It
      allows to monitor the largest number of anti-HIV drugs simultaneously, appearing
      useful in a routine laboratory, and represents an essential step to elucidate the
      utility of a formal therapeutic drug monitoring for the optimal follow-up of HIV
      infected patients.

PMID- 16406834
TI  - To treat or not to treat postpartum pelvic girdle pain with stabilizing
      exercises?
AB  - Women with pelvic girdle pain (PGP) often consult physical therapists for help
      and are treated with different therapies without firm evidence for the
      effectiveness. Two randomized controlled trials have investigated the effect of
      stabilizing exercises for PGP. The most recent study demonstrated significant
      positive results in favour of exercises (Stuge et al. The efficacy of a treatment
      program focusing on specific stabilizing exercises for pelvic girdle pain after
      pregnancy. A randomized controlled trial. Spine 2004a;29(10):351-9), the other
      did not (Mens et al. Diagonal trunk muscle exercises in peripartum pelvic pain: a
      randomized clinical trial. Phys. Ther. 2000;80(12):1164-73). Consequently, the
      two studies provide contradictory advice for treatment of PGP. The question is
      thus, whether stabilizing exercises should be recommended as treatment for PGP.
      Both the studies are of high methodological quality and are comparable with
      regard to subjects studied. However, there are several differences in the
      interventions and these are explored and discussed for better understanding of
      the conflicting results. Exercises that focused on only global muscles showed no
      effect. However, these exercises were not individualized and they were instructed
      by videotape. In the more recent study, exercises that initially focused on local
      muscles, and then gradually added global muscles showed a significant, positive
      effect. Exercises in that study were supervised, corrected, individualized
      concerning choice of exercises, order and dosage, and pain was avoided. This
      comparison indicates that effective treatment of postpartum PGP may be achieved
      when exercises for the entire spinal musculature are included, individually
      guided and adapted to each individual.

PMID- 16406833
TI  - Responses of 6500 households to arsenic mitigation in Araihazar, Bangladesh.
AB  - This study documents the response of 6500 rural households in a 25 km(2) area of
      Bangladesh to interventions intended to reduce their exposure to arsenic
      contained in well water. The interventions included public education, posting
      test results for arsenic on the wells, and installing 50 community wells. Sixty
      five percent of respondents from the subset of 3410 unsafe wells changed their
      source of drinking water, often to new and untested wells. Only 15% of
      respondents from the subset of safe wells changed their source, indicating that
      health concerns motivated the changes. The geo-referenced data indicate that
      distance to the nearest safe well also influenced household responses.

PMID- 16406835
TI  - Evaluation of neonatal intensive care for extremely-low-birth-weight infants.
AB  - Neonatal intensive care for extremely-low-birth-weight (ELBW, 500-999 g) infants
      must be evaluated to determine that it is effective, efficient, and available to
      those who need it. From the late 1970s until the late 1990s in the state of
      Victoria, Australia, neonatal intensive care has been increasingly effective,
      with large increases in the long-term survival rate from 25% in 1979-1980 to 73%
      in 1997, and in the quality-adjusted survival rate from 19% to 59% over the same
      time. Its efficiency has been relatively high and stable over time, comparing
      favourably with many other health-care programmes. It is increasingly available,
      with fewer than 10% of ELBW infants born outside level III perinatal centres in
      the latest era, and proportionally more ELBW infants being offered intensive care
      over time. Neonatal intensive care should be re-evaluated at intervals in the
      future to ensure that its effectiveness, efficiency and availability are
      maintained.

PMID- 16406838
TI  - Chlamydia and programmed cell death.
AB  - Discordant views regarding host cell death induction by Chlamydia are likely
      owing to the different methods used for evaluation of apoptosis. Apoptotic and
      non-apoptotic death owing to both caspase-dependent and -independent activation
      of the Bax protein occur late in the productive growth cycle. Evidence also
      suggests that Chlamydia inhibits apoptosis during productive growth as part of
      its intracellular survival strategy. This is in part owing to proteolytic
      degradation of the BH3-only family of pro-apoptotic proteins in the mitochondrial
      pathway. Chlamydia also inhibits apoptosis during persistent growth or in
      phagocytes, but induces apoptosis in T cells, which suggests that apoptosis has
      an immunomodulatory role in chlamydial infections. The contribution of apoptosis
      in disease pathogenesis remains a focus for future research.

PMID- 16406837
TI  - Interaction of pathogenic mycobacteria with the host immune system.
AB  - Pathogenic mycobacteria, in particular Mycobacterium tuberculosis, the causative
      agent of tuberculosis, have the remarkable capacity to circumvent destruction
      within one of the most hostile cell types of a vertebrate host: the macrophage.
      The ability of pathogenic mycobacteria to survive inside macrophages has been
      known for more than 30 years; yet, only recently have advances in molecular
      genetics, biochemistry, immunology, as well as global analysis of gene
      expression, started to unravel the strategies utilized by these pathogens for
      intracellular persistence. In addition, the definition of key molecules that are
      important for intracellular survival opens the possibility to develop new drugs
      to combat mycobacterial diseases.

PMID- 16406839
TI  - Structural and polarized vibrational studies of pentacaesium
      trihydrogentetraselenate monohydrate.
AB  - Polarized IR and Raman spectra of single crystal were measured at room and at low
      temperature. The polarized IR spectra were measured by transmission and specular
      reflection method. The IR-microscope was used for vibrational measurement of
      small monocrystals. Assignment of the bands is proposed on the basis of oriented
      gas model approximation. The polarized vibrational spectra are discussed in
      relation to the crystal structure and possible proton conductivity and phase
      transition.

PMID- 16406840
TI  - Vibrational spectra and normal co-ordinate analysis of 2-aminopyridine and 2
      amino picoline.
AB  - The Fourier transform infrared (FT-IR) and Raman (FT-R) spectra of 2
      aminopyridine and 2-amino picoline were recorded and the observed frequencies
      were assigned to various modes of vibration in terms of fundamentals by assuming
      Cs point group symmetry. A normal co-ordinate analysis was also carried out for
      the proper assignment of the vibrational frequencies using simple valence force
      field. A complete vibrational analysis is presented here for the molecules and
      the results are briefly discussed.

PMID- 16406841
TI  - From deafness genes to hearing mechanisms: harmony and counterpoint.
AB  - The study of hereditary hearing impairments provides a unique opportunity to deal
      with two objectives simultaneously: (i) identification of the causative genes and
      the underlying pathogenic process in each form of deafness; and (ii) elucidation
      of the molecular and cellular mechanisms of hearing. This review highlights the
      breakthroughs achieved during the past 12 years, with respect to their medical
      impacts and advances in basic scientific knowledge. To date, this research relies
      extensively on mouse models to study human forms of deafness. But, can mouse
      models sustain genetic approaches to study the physiology and pathophysiology of
      the auditory system and to develop and test drugs?

PMID- 16406842
TI  - LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?
AB  - The presence of alpha-synuclein Lewy body pathology is used to distinguish
      Parkinson's disease from parkinsonism, for which a broader spectrum of
      neuropathologies, including tau-immunopositive neurofibrillary tangles and
      ubiquitin inclusions, might accompany nigral neuronal loss. These
      neuropathologies define the endpoint of many neurodegenerative disorders but
      might be symptomatic rather than causative. Mutations in the gene encoding
      leucine-rich repeat kinase 2 (LRRK2) were recently discovered in late-onset
      parkinsonism, the phenotype of which can be clinically and pathologically
      indistinguishable from Parkinson's disease. However, in some kindreds with LRRK2-
      associated disease, pathologically distinct forms of parkinsonism, including
      nigral neuronal loss with Lewy body disease or tau-immunopositive neurofibrillary
      tangles, were discovered. Understanding the molecular function of the LRRK2
      protein and its associated pathways might elucidate the switch between Lewy body
      pathology and neurofibrillary tangles, and holds promise for prospective
      therapeutics that might slow or halt progression of many forms of parkinsonism.

PMID- 16406843
TI  - Emerging medicinal roles for lysophospholipid signaling.
AB  - The two lysophospholipids (LPs) lysophosphatidic acid and sphingosine 1-phosphate
      (S1P) regulate diverse biological processes. Over the past decade, it has become
      clear that medically relevant LP activities are mediated by specific G protein
      coupled receptors, implicating them in the etiology of a growing number of
      disorders. A new class of LP agonists shows promise for drug therapy: the
      experimental drug FTY720 is phosphorylated in vivo to produce a potent S1P
      receptor agonist (FTY720-P) and is currently in Phase III clinical trials for
      kidney transplantation and Phase II for multiple sclerosis. Recent genetic and
      pharmacological studies on LP signaling in animal disease models have identified
      new areas in which interventions in LP signaling might provide novel therapeutic
      approaches for the treatment of human diseases.

PMID- 16406844
TI  - Ex vivo expansion of dendritic-cell-activated antigen-specific CD4+ T cells with
      anti-CD3/CD28, interleukin-7, and interleukin-15: potential for adoptive T cell
      immunotherapy.
AB  - There is an increasing realization that the failure of adoptive therapy with
      cytotoxic T lymphocytes in the autologous setting, at least in part, results from
      the lack of help from antigen-specific CD4+ T cells. To incorporate these cells
      into this treatment strategy, it is not known whether currently used ex vivo
      culture conditions are adequate for expanding and charting these T cells with the
      desired qualities for optimal in vivo activity. In this study, we show that
      stimulation with agonistic antibodies to CD3 plus CD28 (anti-CD3/CD28), a
      commonly used method for CD4+ T cell expansion, is unable to expand dendritic
      cell-activated hepatitis B virus (HBV)-specific CD4+ T cells to clinical relevant
      numbers. Whereas, in combination with interleukin(IL)-7 and IL-15, it leads to a
      4000-fold expansion of HBV-specific CD4+ T cells in 2 weeks. This outcome is
      correlated with the anti-apoptosis effect of IL-7 and IL-15. Importantly, antigen
      specificity is preserved during expansion. Although a late addition of IL-2 to
      the anti-CD3/CD28-expanding cultures also results in robust expansion, this
      expansion condition renders HBV-specific CD4+ T cells more sensitive to cytokine
      withdrawal-, activation-, and transforming growth factor-beta-induced cell death
      compared to those expanded in IL-7 and IL-15. Moreover, NKG2D rather than 4-1BB,
      whose ligands are constitutively expressed on tumor cells, is significantly up
      regulated on IL-7/IL-15-expanded HBV-specific CD4+ T cells, and its engagement
      promotes expansion and interferon-gamma production by these cells and thus may
      serve to provide co-stimulation to T cells once they reach tumor tissues.
      Collectively, these results may have important therapeutic implications for
      adoptive T cell therapy.

PMID- 16406845
TI  - Dostoevsky's epilepsy: Generalized or focal?

PMID- 16406847
TI  - The role of reviews of perinatal deaths.
AB  - Systematic audit of stillbirths and neonatal deaths at an institutional and
      regional level is the first step in the descriptive epidemiology of perinatal
      mortality and a necessary means for identifying the causes of such deaths.
      Uniform classification systems within an organizational jurisdiction enable the
      identification of the major contributing categories, facilitate analysis, and
      enable consideration of possible interventions and strategies for prevention.
      This paper describes the application of the classification systems recently
      developed by the Perinatal Society of Australia and New Zealand (PSANZ), as part
      of a perinatal audit package, to a cohort of 3485 perinatal deaths in Victoria
      over a 5-year period, 2000-2004. There are many other perinatal mortality audit
      systems in place in other jurisdictions, designed to produce the same result,
      i.e. a better understanding of the causes of perinatal mortality and the
      possibilities for prevention.

PMID- 16406846
TI  - On-line identification of the constituents of Buyang Huanwu decoction in pig
      serum using combined HPLC-DAD-MS techniques.
AB  - Buyang Huanwu decoction (BYHWD) is a widely used Chinese traditional compound
      medicine that has proved effective in treating cerebrovascular illnesses;
      however, its active substances have remained unknown. In this paper, serum
      chemistry and combined high-performance liquid chromatography (HPLC), photodiode
      array detection and mass-spectrometry techniques were used to study the
      constituents of BYHWD from pig serum after oral administration. A total of 45
      characteristic HPLC peaks were detected from serum containing drug. The chemical
      structures of nine of the peaks were tentatively elucidated as 7,3'-dihydroxy-4'
      methoxyisoflavone-7-O-glucuronide (P1), 7-hydroxy-4'-methoxyisoflavone-7-O
      glucuronide (P2), 7,2',4'-trihydroxy-3'-methoxyisoflavane-7-O-sulphate (P3), 3
      hydroxy-9,10-dimethoxypterocarpan-3-O-glucuronide (P4), 7,2'-dihydroxy-3',4'
      dimethoxyisoflavane-7-O-glucuronide (P5), 3-hydroxy-9,10-dimethoxypterocarpane-3
      O-sulphate (P6), 4(1H)-quinolinone (P7 or P8), 4-hydroxyquinoline (P8 or P7) and
      oleic acid (P9). All of the identified peaks, with the exception of P9, were
      metabolites of the constituents of BYHWD in vivo.

PMID- 16406848
TI  - Patients with hip fracture: what can be improved?
AB  - Hip fracture is costly from both personal and public health perspectives. Major
      advances in understanding the risk factors for osteoporotic fracture and in
      developing strategies to reduce risk have occurred in recent years. Effective
      interventions to reduce hip fracture risk include vitamin D and calcium
      supplementation, antiresorptive agents such as bisphosphonates and possibly
      estrogen and the anabolic agent teriparatide, fall prevention strategies, and use
      of hip protectors. Current clinical practice regarding hip fracture prevention,
      however, leaves much to be desired. Primary care physicians seeing high-risk
      patients must identify and manage this risk. Radiologists, orthopedic surgeons,
      and rehabilitation medicine physicians who diagnose and treat patients for
      fracture-a major risk factor for subsequent fracture-must refer patients for
      additional assessment and treatment to reduce risk. Appropriate risk factor
      assessment and use of current intervention strategies should markedly reduce the
      numbers of new fractures.

PMID- 16406850
TI  - Should the draft chimpanzee sequence be finished?
AB  - Owing to the availability of genome working drafts (WDs), current comparative
      sequence studies are frequently performed on a genome-wide scale. In this
      article, we appraise the utility of WD sequences in the detection of genomic
      differences in closely related species. We compared human DNA sequences with
      draft and high-quality versions of the corresponding chimpanzee loci to reveal
      the overall high quality of the chimp WD sequence. Nevertheless, a significant
      proportion of the differences between WD and high-quality sequences we observed
      can be attributed to sequencing errors in the draft. Although we suggest methods
      to reduce the number of such false positives efficiently, our study emphasizes
      the benefit expected from finishing the chimpanzee genome sequence.

PMID- 16406851
TI  - Random effect modelling of patient-related risk factors in orthopaedic
      procedures: results from the Dutch nosocomial infection surveillance network
      'PREZIES'.
AB  - In the Dutch surveillance for surgical site infections (SSIs), data from 70277
      orthopaedic procedures with 1895 SSIs were collected between 1996 and 2003. The
      aims of this study were: (1) to analyse the trends in SSIs associated with Gram
      positive and Gram-negative bacteria; (2) to estimate patient-related risk factors
      for deep and superficial SSIs after all orthopaedic procedures, with special
      attention to primary total hip arthroplasty (THA); and (3) to analyse inherent
      differences in infection risk between hospitals. A random effect model was used
      to estimate the odds ratios of patient-related risk factors for developing an
      SSI, and to describe the distribution of the most widespread bacterial species
      responsible for SSIs among hospitals. Gram-positive organisms, mainly
      staphylococci, were the main cause of both deep (84.0%) and superficial SSIs
      (69.1%) after orthopaedic procedures. The percentage of SSIs after THA caused by
      coagulase-negative staphylococci decreased over the surveillance period, while
      the contribution of Staphylococcus aureus increased. Temporary elevations in the
      incidence of the most widespread pathogen species were observed within hospitals.
      Patient-related factors such as the National Nosocomial Infections Surveillance
      System risk index or age had little effect on the predictive power of the random
      effect models. This study underlines the usefulness of a random effect model,
      which adjusts risk estimates for random variation between hospitals, in a
      multicentre study on risk factors for SSIs.

PMID- 16406852
TI  - Vertical distributions of 210Pb excess, 7Be and 137Cs in selected grass covered
      soils in Southeast Queensland, Australia.
AB  - Net accumulated areal activity densities and profiles of (210)Pb(ex), (7)Be and
      (137)Cs in the surface 10 cm of the soil are reported for eight sites in
      Southeast Queensland, Australia. Areal activity densities of (210)Pb(ex) and
      (7)Be varied from 1,080 to 4,100 Bqm(-2) and from 176 to 778 Bqm(-2),
      respectively. A significant (p < 0.001) portion of the variance (R(2) > 0.99) in
      their vertical distributions was explained by depth in the profile using an
      exponential function. Around 85% of accumulated (210)Pb(ex) was present in the
      surface 10 cm of the soil. Beryllium-7 was mainly confined to the grass and
      surface 2 cm of the soil. Average penetration half-depths of 3.6 +/- 0.2 and 0.3
      +/- 0.1cm were determined for (210)Pb(ex) and (7)Be, respectively. Areal activity
      densities of global fallout (137)Cs varied from 10 to 361 Bqm(-2). Its signal was
      well mixed within the surface 10 cm. Comparison of the measured (137)Cs values to
      the estimated input value for the region ( approximately 490 Bqm(-2)) and
      profiling of a 1m deep soil core suggests a vertical migration of (137)Cs over
      the past decades. The paleo-radon activity flux determined from the (210)Pb(ex)
      areal activity density (5.1 +/- 0.9 mBqm(-2) s(-1)) was not statistically
      different to that measured using activated charcoal cups (5.5 +/- 0.4 mBqm(-2) s(
      1)), tending to suggest that Southeast Queensland is neither a net source nor a
      net sink of (210)Pb-bearing aerosols.

PMID- 16406853
TI  - Down-regulation of P-glycoprotein expression in MDR breast cancer cell MCF-7/ADR
      by honokiol.
AB  - P-glycoprotein accounts for the most intrinsic and acquired cancer multidrug
      resistance. To inhibit the expression of P-glycoprotein is one of the effective
      ways to reverse cancer drug resistance. Honokiol, a naturally occurring compound,
      has been demonstrated to combat cancer through mechanisms including inhibition of
      angiogenesis and induction of apoptosis. Here, we show that honokiol down
      regulated the expression of P-glycoprotein at mRNA and protein levels in MCF
      7/ADR, a human breast MDR cancer cell line. The down-regulation of P-glycoprotein
      was accompanied with a partial recovery of the intracellular drug accumulation,
      and of the sensitivities toward adriamycin. This study reveals a novel function
      of honokiol as an anti-cancer agent.

PMID- 16406854
TI  - Trans-metastasis hepatectomy: results of a 21-case study.
AB  - AIM: The aim of this study was to report the feasibility and efficiency of a new
      approach, called post-RF trans-metastasis hepatectomy (PRFTMH). This technique
      consists in using RF to first ablate an ill-located liver metastasis (LM) along
      the planned hepatectomy resection line, the only one possible for volumetric
      reasons, and then to perform the hepatectomy passing via this initially ablated
      LM. MATERIAL AND METHODS: Twenty-one patients were treated with PRFTMH between
      January 2000 and May 2004. Thirteen of them had a primary colorectal tumour, four
      had a primary endocrine tumour and four had miscellaneous primaries. The mean
      number of LMs per patient was 13.8 (10.7 for primary colorectal tumours and 22.2
      for primary endocrine tumours). Pre-operative hypertrophy of the future remaining
      liver was obtained by selective portal vein embolisation in 11 patients. RESULTS:
      One patient died post-operatively (4.7%) and five developed complications (24%).
      No local recurrence has occurred at the site of PRFTMH after a median follow-up
      of 19.4 months (range: 47-7), demonstrating the efficacy of this technique. All
      patients, except the patient who died post-operatively, are currently alive, and
      the median survival rate has not yet been attained, after a median follow-up of
      19.4 months. CONCLUSION: PRFTMH combining RF ablation and trans-metastasis
      hepatectomy is a new and safe technique, allowing a curative approach to be
      proposed to some patients with unresectable bilateral LMs.

PMID- 16406860
TI  - Upper tract urothelial carcinoma.

PMID- 16406861
TI  - How far are we from a urothelial gene chip?

PMID- 16406862
TI  - The continuing search for meaningful prognostic information from prostate biopsy.

PMID- 16406863
TI  - Tissue microarrays and their relevance to the urologist.
AB  - PURPOSE: We review important aspects of TMA methodology and discuss its wide
      range of clinical applications with particular emphasis on key clinical studies.
      We also provide an update on recent and projected uses of this technology to help
      the urologist improve care in oncology patients. MATERIALS AND METHODS: A
      directed MEDLINE literature review of TMAs was performed. Important publications
      that have shaped our understanding of TMAs were selected for review. They were
      augmented by manual searches and our personal bibliographic collections. RESULTS:
      The TMA is a high throughput molecular biology technique that can significantly
      accelerate the processing of a large number of tissue specimens with excellent
      quality, good reliability and the preservation of original tissue. TMA studies
      demonstrate their accuracy and reliability compared to those of standard
      histological techniques and correlate with clinicopathological information to
      determine disease progression and prediction of the clinical outcome.
      CONCLUSIONS: This review represents an overview and update for the urologist on
      TMAs and their clinical applications in urological oncology. In the future it is
      anticipated that the outcomes of this method will be used to assist in the
      diagnosis, prognosis and development of novel therapies in individual patients.

PMID- 16406864
TI  - Secondary hormonal therapy for advanced prostate cancer.
AB  - PURPOSE: Androgen ablation remains the cornerstone of management for advanced
      prostate cancer. Therapeutic options in patients with progressive disease
      following androgen deprivation include antiandrogen withdrawal, secondary
      hormonal agents and chemotherapy. Multiple secondary hormonal agents have
      clinical activity and the sequential use of these agents may lead to prolonged
      periods of clinical response. We provide a state-of-the-art review of the various
      agents currently used for secondary hormonal manipulation and discusses their
      role in the systemic treatment of patients with prostate cancer. MATERIALS AND
      METHODS: A comprehensive review of the peer reviewed literature was performed on
      the topic of secondary hormonal therapies, including oral antiandrogens, adrenal
      androgen inhibitors, corticosteroids, estrogenic compounds, gonadotropin
      releasing hormone antagonists and alternative hormonal therapies for advanced
      prostate cancer. RESULTS: Secondary hormonal therapies can provide a safe and
      effective treatment option in patients with AIPC. The use of steroids and
      adrenolytics, such as ketoconazole and aminoglutethimide, has resulted in
      symptomatic improvement and a greater than 50% prostate specific antigen decrease
      in a substantial percent of patients with AIPC. A similar clinical benefit has
      been demonstrated with estrogen based therapies. Furthermore, these therapies
      have demonstrated a decrease in metastatic disease burden. Other novel hormonal
      therapies are currently under investigation and they may also show promise as
      secondary hormonal therapies. Finally, guidelines from the United States Food and
      Drug Administration Prostate Cancer Endpoints Workshop were reviewed in the
      context of developing new agents. CONCLUSIONS: Secondary hormonal therapy serves
      as an excellent therapeutic option in patients with AIPC in whom primary hormonal
      therapy has failed. Practicing urologists should familiarize themselves with
      these oral medications, their indications and their potential side effects.

PMID- 16406865
TI  - Alfuzosin for symptomatic benign prostatic hyperplasia: long-term experience.
AB  - PURPOSE: Evidence of the long-term efficacy and safety of alfuzosin treatment for
      LUTS indicative of BPH was examined. MATERIALS AND METHODS: An English literature
      search of MEDLINE, PubMed and proceedings from scientific meetings from 1974 to
      2004 was done. Search terms included benign prostatic hyperplasia, alfuzosin,
      treatment, alpha(1)-adrenergic receptor blocker, long-term, followup, lower
      urinary tract symptoms, complications or adverse events, sexual, retention and
      cardiovascular. RESULTS: Currently alpha(1)-adrenergic receptor blocking agents
      are first line treatment for BPH. Although all alpha-blocking compounds show
      similar levels of efficacy for LUTS treatment, newer agents such as alfuzosin
      tend to demonstrate improved selectivity for the prostate and bladder with few
      vasodilatory effects and they have tolerability advantages over older alpha
      blocking compounds. Immediate, sustained and newer extended release alfuzosin
      formulations significantly improve LUTS indicative of BPH but extended release
      alfuzosin may be more convenient to administer and it tends to show better
      vasodilatory tolerability than the older immediate release formulation.
      CONCLUSIONS: When used to treat BPH, alfuzosin provides symptom relief, decreased
      residual post-void urine volume and a decreased risk of acute urinary retention,
      which are maintained during long-term use. Most vasodilatory side effects occur
      early in treatment and they become less frequent thereafter. Patient quality of
      life also improves with maximal improvements observed after 12 months of
      treatment. Continued study will further clarify the physiological, clinical and
      personal benefits produced by alfuzosin when used for the management of LUTS
      indicative of BPH.

PMID- 16406866
TI  - Victor Fray Marshall: twentieth century renaissance urologist.
AB  - PURPOSE: Victor Fray Marshall (1913 to 2001) contributed to advancements in a
      variety of fields within urology, including incontinence, oncology, stone disease
      and pediatrics. MATERIALS AND METHODS: We reviewed historical records from the
      New York Hospital archives as well as the original publications of Marshall.
      Personal experiences of former residents and others were recounted. RESULTS:
      While Marshall may be most recognized for Marshall-Marchetti-Krantz
      vesicourethral suspension, designed to correct stress urinary incontinence, he
      was among the earliest advocates of surgical extirpation for bladder cancer and
      helped introduce the use of urinary cytology for the diagnosis of urothelial
      malignancy. At the same time Marshall contributed to the development of
      ureteroscopy for stone disease. His contributions to pediatric urology include
      the description of a nonrefluxing ureteral re-implantation technique for the
      surgical correction of reflux as well as his investigation of the embryology and
      surgical repair of bladder exstrophy. CONCLUSIONS: The contributions of Victor
      Marshall to urology are notable in breadth and significance.

PMID- 16406867
TI  - Impact of body mass index on survival of patients with surgically treated renal
      cell carcinoma.
AB  - PURPOSE: Population studies link increased BMI with an increased risk of cancer
      and cancer mortality and in particular a greater risk of RCC. We evaluated the
      impact of BMI and other clinical/pathological characteristics on survival in
      patients with RCC treated with radical or partial nephrectomy. MATERIALS AND
      METHODS: Between 1995 and 2003 patients undergoing radical (760) or partial (399)
      nephrectomy for RCC were entered into a database. BMI data were available on
      1,137 of 1,159 (98%). Demographic and clinical/pathological parameters were
      analyzed. World Health Organization BMI definitions (normal-less than 25 kg/m(2),
      overweight-25 to 29.9 kg/m(2), obese-30 kg/m(2) or more) were used. RESULTS: A
      total of 75% of patients had greater than normal BMI with 472 (41.5%) overweight
      and 387 (34.0%) obese. Median followup was 33 months with a median overall
      survival of 110 months and a 5-year overall survival probability of 0.79. BMI
      categories were similar in age, gender, smoking status, presenting symptoms,
      tumor size, stage, and type of surgery. Significant increases in blood loss and
      operative time (p <0.05) were seen with increasing BMI. Although BMI 30 kg/m(2)
      or greater was associated with a higher proportion of clear cell histology (p =
      0.002), it did not translate into an increased pathological stage, or incidence
      of metastasis. Multivariate analysis revealed age older than 65 years, systemic
      symptoms, surgery type, and pathological stage impacted overall survival (p
      <0.05). CONCLUSIONS: Although an increased BMI was associated with a greater
      proportion of clear cell histology, comorbidity, and surgical morbidity, BMI did
      not adversely impact overall or progression-free survival.

PMID- 16406868
TI  - Rare expression of KIT and absence of KIT mutations in high grade renal cell
      carcinoma.
AB  - PURPOSE: RCCs with sarcomatoid differentiation have been reported to frequently
      express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevectrade
      mark) may be effective treatment for these aggressive tumors. We determined the
      frequency of KIT expression and mutation in a large series of high grade RCCs.
      MATERIALS AND METHODS: We identified 194 patients who underwent nephrectomy for
      unilateral, sporadic nuclear grade 4 RCC between 1970 and 2002, including 123
      with sarcomatoid differentiation. Sections from representative paraffin embedded
      tissue blocks were immunostained in an autostainer using
      ethylenediaminetetraacetic acid antigen retrieval, a polyclonal KIT antibody and
      the avidin-biotin peroxidase complex method. Mutational analysis was performed in
      all immunopositive and select negative cases by polymerase chain reaction
      amplification of KIT exons 9, 11, 13 and 17. RESULTS: Only 7 tumors (3.6%) showed
      KIT expression, including 5 of the 123 (4.1%) with sarcomatoid differentiation.
      Four of the 7 tumors showed focal staining only. No mutations were identified in
      the 7 positive cases or in 8 randomly selected negative samples. Death from RCC
      occurred in all 7 patients with KIT positive tumors at a median of 0.6 years
      (range 0.3 to 2.3) and in 139 of 187 with KIT negative tumors at a median of 0.8
      years (range 0 to 10.2). CONCLUSIONS: KIT expression was identified in less than
      5% of high grade RCCs with or without sarcomatoid differentiation but none of the
      tumors showed KIT mutations. These findings indicate that imatinib therapy is
      unlikely to be effective in patients with high grade RCC.

PMID- 16406869
TI  - A clinical trial with chimeric monoclonal antibody WX-G250 and low dose
      interleukin-2 pulsing scheme for advanced renal cell carcinoma.
AB  - PURPOSE: WX-G250 is a chimeric monoclonal antibody that binds to carbonic
      anhydrase IX(G250/MN), which is present on greater than 95% of RCCs of the clear
      cell subtype. The suggested working mechanism of WX-G250 is by ADCC. Because the
      number of activated ADCC effector cells can be increased by a low dose
      interleukin-2 pulsing schedule, a multicenter study was initiated to investigate
      whether WX-G250 combined with LD-IL-2 could lead to an improved clinical outcome
      in patients with progressive RCC. MATERIALS AND METHODS: A total of 35 patients
      with progressive clear cell RCC received weekly infusions of WX-G250 for 11 weeks
      combined with a daily LD-IL-2 regimen. Patients were monitored longitudinally for
      ADCC capacity. Radiological assessment of metastatic lesions was performed at
      week 16 and regularly until disease progression. RESULTS: A durable clinical
      benefit was achieved in 8 of 35 patients (23%), including 3 with a partial
      response and 5 with stabilization at 24 weeks or greater. Mean survival was 22
      months. In general treatment was well tolerated with little toxicity. The number
      of effector cells increased during treatment but lytic capacity per cell did not
      increase. ADCC and clinical outcome did not appear to correlate. CONCLUSIONS: WX
      G250 combined with LD-IL-2 in patients with metastatic RCC is safe and well
      tolerated. With a substantial clinical benefit and a median survival of 22 months
      in patients with metastatic RCC who have progressive disease at study entry
      combination therapy showed increased overall survival compared to WX-G250
      monotherapy. Survival was at least similar to that of currently used cytokine
      regimens but with a favorable toxicity profile.

PMID- 16406870
TI  - Combining hand assisted laparoscopic nephroureterectomy with cystoscopic
      circumferential excision of the distal ureter without primary closure of the
      bladder cuff--is it safe?
AB  - PURPOSE: We have previously described our technique of combining HAL-NU using
      early ureteral ligation with simultaneous cystoscopic circumferential excision of
      the distal intramural ureter without primary closure of the bladder cuff. We
      report the oncological sequelae in patients who underwent HAL-NU using our
      technique of complete ureteral removal. MATERIALS AND METHODS: We retrospectively
      evaluated all patients who underwent HAL-NU from April 1999 through July 2004.
      Cystograms were performed 1 week postoperatively in all patients. Pathological
      findings were reviewed. Cystoscopy was performed every 3 months to assess bladder
      recurrences. Upper tract imaging was performed postoperatively and then annually.
      The locations of recurrence and need for adjuvant treatment were assessed.
      RESULTS: A total of 49 patients with an average age of 67 years underwent HAL-NU.
      Gravity cystography confirmed that bladder defects had completely sealed at 1
      week in all patients. Mean followup was 10.6 months (median 10, range 1 to 52).
      Of the patients 20 (49%) had bladder tumors postoperatively. Two patients were
      found to have advanced stage disease, leading to chemotherapy with radiation
      therapy in 1 and radical cystectomy in the other at 4 and 14 months,
      respectively. A total of 25 patients had postoperative pelvic imaging. Four
      patients with pathological stage T2 (1) and T3 (3) had metastatic disease at
      followup. One patient was known to have pulmonary metastases preoperatively and
      HAL-NU was performed for refractory hematuria. Two patients were noted to have
      distant metastases to the liver, lung and bone at 1 and 3 months postoperatively,
      respectively. One patient was found to have distant metastases to the liver and
      retroperitoneal lymph nodes 2 years after surgery. No patients were found to have
      local pelvic or peritoneal metastases. CONCLUSIONS: HAL-NU with cystoscopic
      excision of the distal ureter is feasible, safe and effective for upper tract
      transitional cell carcinoma. Oncological sequelae are comparable to results after
      open surgery. There is no evidence to suggest pelvic or peritoneal tumor seeding
      since no cases of pelvic or abdominal recurrence were discovered after surgery,
      while allowing the bladder defect to close spontaneously with catheter drainage.
      Our technique of ureterectomy ensures complete removal of the entire ureter,
      eliminating the possibility of ureteral stump recurrences. Early ligation of the
      ureter prevents tumor migration during renal manipulation, minimizing the risk of
      local tumor recurrences postoperatively.

PMID- 16406872
TI  - Bilateral metachronous ureteral and renal pelvic carcinomas: incidence, clinical
      presentation, histopathology, treatment and outcome.
AB  - PURPOSE: Metachronous bilateral UUTTs are rare. The authors reported baseline and
      long-term followup data for all patients diagnosed in Western Sweden during a 28
      year period. MATERIALS AND METHODS: We performed a clinical and histopathological
      analysis of all patients in Western Sweden surgically treated for ureteral and
      renal pelvic tumors from 1971 to 1998. RESULTS: Of 768 patients a contralateral
      UUTT developed in 24 (3.1%) after a median of 46 months (range 2 to 232). The
      projected incidence after initial UUTT diagnosis was 2.7%, 5.8% and 6.5% at 5, 10
      and 15 years, respectively. Median age of the 24 patients at initial UUTT
      diagnosis was 67 years and the median age at death was 77 years. Bladder cancer
      was significantly more common among patients with bilateral UUTT compared to
      those with unilateral UUTT (83% vs 31%, p <0.0001). Routine followup urography
      was normal in 9 patients 2 to 11 months before the diagnosis of the contralateral
      UUTT. Nine patients died of UUTT and 5 patients died of bladder cancer.
      CONCLUSIONS: Bilateral subsequent upper tract tumors are rare, in general
      diagnosed at an older age and associated with short survival. Many patients die
      of bladder cancer and it may be possible to improve survival if the bladder
      cancer is treated early and aggressively. Routine followup urography is not
      indicated among patients with a tumor-free bladder and a history of UUTT.

PMID- 16406874
TI  - Risk factors for upper tract recurrence in patients undergoing long-term
      surveillance for stage ta bladder cancer.
AB  - PURPOSE: While the evidence is clear that patients with carcinoma in situ or high
      grade T1 TCC of the bladder are at higher risk for developing UUT tumors, the
      role of imaging the UUT in patients with Ta tumors remains controversial. We
      hypothesized that the number and frequency of recurrences in patients with Ta
      disease would allow us to identify a population who should undergo routine UUT
      surveillance. MATERIALS AND METHODS: We reviewed our database of 375 patients who
      underwent resection of a stage Ta TCC between 1975 and 1995. Median followup was
      6 years. Patients were stratified according to the presence of an UUT occurrence,
      rate and timing of superficial recurrences, and grade of the initial bladder
      tumor. RESULTS: Among the 375 patients 50% had no bladder recurrence, 25% had 1
      tumor, 15% had 2 tumors, and 10% had 3 or more tumors. Average time between
      tumors was 17 months. UUT tumor developed in 13 patients (3.4%) at an average of
      22 months after their initial bladder tumor. A high risk group consisting of
      patients who had 2 or more bladder recurrences recurring within 12 months of each
      other were at 4.5-fold the risk of UUT tumor. CONCLUSIONS: Stage Ta bladder
      cancer patients with 2 or more recurrences of bladder tumors with a median of
      less than 12 months between recurrences are at higher risk for developing an UUT
      tumor and should be considered for more frequent UUT surveillance.

PMID- 16406875
TI  - Effect of preoperative delay on survival in patients with bladder cancer
      undergoing cystectomy in Quebec: a population based study.
AB  - PURPOSE: In Canada there is growing concern that waiting time for cancer surgery
      has been increasing. We used population based data to estimate the average PD for
      RC in Quebec and assess whether delayed surgery has a negative impact on long
      term survival. MATERIALS AND METHODS: We used the provincial billing database of
      the maladie du Quebec to identify all patients with bladder cancer 18 years or
      older who underwent RAMQ from 1990 to 2002. PD was calculated as the time elapsed
      between the most recent transurethral resection and the date of RC. Patients were
      categorized according to PD tertiles into 3 groups, namely 1) 20 or less, 2) 21
      to 47 and (C) 48 days or greater. Cox proportional hazards models were used to
      assess the effect of PD on overall survival, while adjusting for patient and
      provider factors. RESULTS: During the study period 1,592 radical cystectomies
      were performed. Overall median PD was 33 days (95% CI 30 to 35). Median PD
      increased from 23 days in 1990 to 50 in 2002. After adjusting for calendar year,
      and patient and provider variables there were no significant differences in
      survival among the 3 delay categories. However, patients subject to greater than
      12 weeks of delay were at 20% greater risk for dying (95% CI 1.0 to 1.5, p =
      0.051). CONCLUSIONS: In line with previous reports PD greater than 12 weeks seems
      to be associated with a worse long-term prognosis.

PMID- 16406877
TI  - Intraoperative sentinel node detection improves nodal staging in invasive bladder
      cancer.
AB  - PURPOSE: We evaluated intraoperative SN detection in patients with invasive
      bladder cancer during radical cystectomy in conjunction with extended
      lymphadenectomy. MATERIALS AND METHODS: A total of 75 patients with invasive
      bladder cancer underwent radical cystectomy with extended lymphadenectomy. SNs
      were identified by preoperative lymphoscintigraphy, intraoperative dynamic
      lymphoscintigraphy and blue dye detection. An isotope (70 MBq (99m)Tc
      nanocolloid) and Patent Blue(R) blue dye were injected peritumorally via a
      cystoscope. Excised lymph nodes were examined ex vivo using a handheld gamma
      probe. Identified SNs were evaluated by extended serial sectioning, hematoxylin
      and eosin staining, and immunohistochemistry. RESULTS: At lymphadenectomy an
      average of 40 nodes (range 8 to 67) were removed. Of 75 patients 32 (43%) were
      lymph node positive, of whom 13 (41%) had all lymph node metastases located only
      outside of the obturator spaces. An SN was identified in 65 of 75 patients (87%).
      In 7 patients an SN was recognized when the nodal basins were assessed with the
      gamma probe after lymphadenectomy and cystectomy. Of the 32 lymph node positive
      cases 26 (81%) had a positive (metastatic) SN. Thus, the false-negative rate was
      6 of 32 cases (19%). Five false-negative cases had macrometastases and/or
      perivesical metastases. In 9 patients (14%) the SN contained micrometastases
      (less than 2 mm), in 5 of whom the micrometastasis was the only metastatic
      deposit. CONCLUSIONS: SN detection is feasible in invasive bladder cancer,
      although the false- negative rate was 19% in this study. Extended serial
      sectioning and immunohistochemistry revealed micrometastases in SNs in 9 patients
      and radio guided surgery after the completion of lymphadenectomy identified SNs
      in an additional 7. We believe that the technique that we used in this study
      improved nodal staging in these 16 of 65 patients (25%).

PMID- 16406881
TI  - Predicting life expectancy in men with clinically localized prostate cancer.
AB  - PURPOSE: The choice of appropriate management for localized prostate cancer
      depends in part on the estimated life expectancy of a man. Little is known about
      the accuracy of existing rules for deriving these estimates. We developed a new
      prediction rule and examined the accuracy of 2 others in our data set. MATERIALS
      AND METHODS: A retrospective cohort was assembled, consisting of 506 men who were
      diagnosed or received initial treatment at a community based, tertiary care
      health center between 1987 and 1989 for clinically localized prostate cancer
      (stages A, B, I, II or T1-2N0M0) and had at least 13 years of followup. Most
      patients did not have prostate specific antigen levels available. Proportional
      hazards regression was used to create a nomogram for deriving survival estimates.
      Discrimination of the new and external prediction rules was assessed by the c
      statistic. Calibration curves compared predicted to actual survival at 10 years.
      RESULTS: Estimates for survival at 5, 10 and 15 years, and for median life
      expectancy were determined. Discrimination was modest with a c-statistic of 0.73.
      The rules of Albertsen and Tewari et al had comparable discrimination in our data
      with a c-statistic of 0.71 and 0.70, respectively. Predicted life expectancy
      according to our rule and that of Tewari approximated actual survival experience.
      Predictions according to the Albertsen study underestimated actual survival in
      our group but in consistent fashion. CONCLUSIONS: Overall life expectancy can be
      predicted with a moderate degree of accuracy, sufficient for informing patient
      clinician discussions but inadequate as the only determinant of the optimal
      management approach.

PMID- 16406879
TI  - Predictive value of N-acetylglucosaminyltransferase-V for superficial bladder
      cancer recurrence.
AB  - PURPOSE: GnT-V is an enzyme that catalyzes beta1-6 branching of N
      acetylglucosamine on asparagine (N)-linked oligosaccharides of cell proteins. GnT
      V expression has been closely related to malignant potentials in colon cancer,
      brain cancer and hepatocellular carcinoma. We determined whether GnT-V expression
      is predictive of superficial bladder cancer recurrence. MATERIALS AND METHODS:
      The cohort comprised 60 consecutive patients with first time superficial bladder
      cancer treated with transurethral resection. None of the patients received
      prophylactic intravesical therapy until recurrence. Paraffin embedded tumor
      specimens were immunohistochemically examined by the avidin-biotin peroxidase
      method using monoclonal antibody against GnT-V. Kaplan-Meier survival curves were
      generated to determine disease-free survival. Univariate and multivariate
      analyses were done to compare GnT-V expression to other clinical and pathological
      variables. RESULTS: GnT-V expression correlated inversely with tumor grade and
      stage. The positive incidence of GnT-V in G1 to G3 tumors was 7 of 9 (78%), 21 of
      43 (49%) and 3 of 8 (38%), respectively. GnT-V was positive in 26 of 44 cases of
      pTa (60%) and in 5 of 16 of pT1 (31%) disease. The 31 patients with positive GnT
      V expression had significantly higher disease-free survival than the 29 with
      negative GnT-V expression (log rank test p = 0.0034). Multivariate analysis
      revealed that patient age, pT, grade and negative GnT-V expression were
      independent predictors of recurrence (p = 0.015, 0.001, 0.019 and 0.011,
      respectively). CONCLUSIONS: Immunohistochemical detection of GnT-V is an
      independent predictor of superficial bladder cancer recurrence.

PMID- 16406882
TI  - Prostate specific antigen isoforms and human glandular kallikrein 2--which offers
      the best screening performance in a predominantly black population?
AB  - PURPOSE: Free prostate specific antigen, complexed PSA and human glandular
      kallikrein 2 have independently been tested against the gold standard of total
      PSA for prostate cancer screening in largely white populations. With the
      incidence of prostate cancer much higher in black men, we sought to evaluate
      these markers simultaneously in a predominantly black population. MATERIALS AND
      METHODS: A total of 138 men, of whom 108 were black, underwent ultrasound guided
      biopsy of the prostate for tPSA levels greater than 2.5 ng/ml or an abnormal
      digital rectal examination. Sera were drawn before biopsy and analyzed for tPSA,
      fPSA, cPSA and hK2 concentrations using standard methods (hK2 assay is for
      research use only, not for use in diagnostic procedures). The areas under the
      receiver operator characteristic curves were determined for each marker as well
      as biomarker combinations. Additionally, each parameter's specificity, positive
      and negative predictive values, and theoretical screening efficiency were
      assessed at or above the 95% sensitivity level. RESULTS: A total of 43 (31.1%)
      men had prostate cancer by biopsy. While the AUC for %fPSA was statistically the
      highest (0.822, p <0.001), cPSA offered the highest specificity (31.6%) and
      positive predictive power (31.7%) of any of the tested biomarkers at comparable
      sensitivity (greater than 95%). The calculated efficiency of cPSA (51.4%) was
      also higher than the other markers. Nearly 20% of biopsies would be avoided using
      cPSA vs standard tPSA screening methods. CONCLUSIONS: Comparing the major PSA
      isoforms and hK2, cPSA alone appears to offer superior diagnostic discrimination
      for cancer detection in a predominantly black population.

PMID- 16406883
TI  - Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the
      risk of prostate cancer in white and black Americans.
AB  - PURPOSE: XRCC1 and APE1 are enzymes involved in the repair of DNA strand breaks
      and base damage that arise from various endogenous and exogenous oxidants. We
      determined whether polymorphisms in XRCC1 and APE1 increase the risk of prostate
      cancer. MATERIALS AND METHODS: We performed a case-control study in 228 white
      American men, 124 black American men, and 335 age, sex and race matched controls.
      Polymorphisms at codon 399 in XRCC1, and at codons 51 and 148 in APE1 were
      determined using an restriction fragment length polymorphism method. Frequencies
      were compared between cases and controls. RESULTS: A significantly increased risk
      of prostate cancer was observed in white men with the XRCC1(399Gln) allele (OR
      1.6, 95% CI 1.1 to 2.4). When APE1 and XRCC1 polymorphisms were evaluated
      together, we found an increased risk of the
      XRCC1(399Arg/Gln+Gln/Gln)/APE1(51Gln/Gln) (OR 4.0, 95% CI 1.3 to 12.5) and
      XRCC1(399Arg/Gln+Gln/Gln)/APE1(148Asp/Asp) (OR 2.9, 95% CI 1.4 to 6.1) genotypes
      in white men. Significant associations were found between combined genotypes and
      prostate cancer risk with a dose-effect relationship in white men (trend test p =
      0.035 and 0.039, respectively). No significant associations were observed between
      polymorphisms in these genes and prostate cancer risk in black men. CONCLUSIONS:
      Our results suggest that inherited variability in DNA repair capacity, as
      reflected by polymorphisms in XRCC1 and APE1, is a risk factor for prostate
      cancer.

PMID- 16406885
TI  - Transrectal prostate biopsy and fiducial marker placement in a standard 1.5T
      magnetic resonance imaging scanner.
AB  - PURPOSE: We investigated the accuracy and feasibility of a system that provides
      transrectal needle access to the prostate concurrent with 1.5 Tesla MRI which
      previously has not been possible. MATERIALS AND METHODS: In 5 patients with
      previously diagnosed prostate cancer, MRI guided intraprostatic placement of gold
      fiducial markers (4 procedures) and/or prostate biopsy (3 procedures) was
      performed using local anesthesia. RESULTS: Mean procedure duration was 76 minutes
      and all patients tolerated the intervention well. Procedure related adverse
      events included self-limited hematuria and hematochezia following 3 of 8
      procedures (all resolved in less than 1 week). Mean needle placement accuracy was
      1.9 mm for the fiducial marker placement studies and 1.8 mm for the biopsy
      procedures. Mean fiducial marker placement accuracy was 4.8 mm and the mean
      fiducial marker placement accuracy transverse to the needle direction was 2.6 mm.
      All patients who underwent the procedure were able to complete their course of
      radiotherapy without delay or complication. CONCLUSIONS: While studies of
      clinical usefulness are warranted, transrectal 1.5 T MRI guided prostate biopsy
      and fiducial marker placement is feasible using this system, providing new
      opportunities for image guided diagnostic and therapeutic prostate interventions.

PMID- 16406886
TI  - Risk of prostate cancer on first re-biopsy within 1 year following a diagnosis of
      high grade prostatic intraepithelial neoplasia is related to the number of cores
      sampled.
AB  - PURPOSE: We determined the influence of the extent of needle biopsy sampling on
      the detection rate of cancer on first biopsy within 1 year following a diagnosis
      of HGPIN. MATERIALS AND METHODS: We identified 791 patients with HGPIN on the
      initial biopsy who had a followup biopsy within 1 year of their diagnosis. The
      mean interval from diagnosis of HGPIN to re-biopsy was 4.6 months. In the initial
      biopsy with HGPIN, 323 men had 8 or more cores (median 10, range 8 to 26) and 332
      men had 6 core biopsies. RESULTS: In the 6 core initial sampling group, the risk
      of cancer on re-biopsy was 20.8% compared to only 13.3% following an initial 8
      core or more sampling (p = 0.011). With 6 core biopsies for both the initial and
      re-biopsy the risk of cancer was 14.1% (group 1). With an initial 6 core biopsy
      and 8 core or more biopsy on followup, the risk of cancer was 31.9% (group 2).
      With 8 core or more biopsy sampling for both initial and repeat biopsies, the
      risk for cancer was 14.6% (group 3). The differences between groups 1 and 3 as
      compared to group 2 were statistically significant (p = 0.001 and p <0.0001,
      respectively). CONCLUSIONS: With relatively poor sampling (6 cores) on the
      initial biopsy, associated cancers are missed resulting in only HGPIN on the
      initial biopsy, and with relatively poor sampling on re-biopsy there is also a
      relatively low risk of finding cancer on re-biopsy (group 1). With poor sampling
      on the initial biopsy and better sampling on re-biopsy, some of these initially
      missed cancers are detected on re-biopsy yielding a higher detection of cancer
      (group 2). Sampling more extensively on the initial biopsy detects many
      associated cancers, such that when only HGPIN is found they often represent
      isolated HGPIN. Therefore, re-biopsy even with good sampling does not detect many
      additional cancers (group 3). Our study demonstrates that the risk of cancer on
      biopsy within 1 year following a diagnosis of HGPIN (13.3%) is not that
      predictive of cancer on re-biopsy if good sampling (8 or more cores) is initially
      performed. For patients diagnosed with HGPIN on extended initial core sampling, a
      repeat biopsy within the first year is unnecessary in the absence of other
      clinical indicators of cancer.

PMID- 16406887
TI  - Prostate biopsy tumor extent but not location predicts recurrence after radical
      prostatectomy: results from CaPSURE.
AB  - PURPOSE: Prostate cancer biopsy information is important for patient risk
      assessment. Although the number and extent of positive biopsies have been used to
      predict recurrence, the impact of positive biopsy location and contiguity is less
      clear. We compared the ability of positive prostate biopsy location and pattern
      with number and percent positive biopsies to predict recurrence after RP.
      MATERIALS AND METHODS: From CaPSURE we identified 2,037 men treated with RP from
      1992 to 2002 for whom detailed biopsy information and 2 or more followup PSA
      values were available. Treatment failure was defined as 2 consecutive PSA values
      of 0.2 ng/ml or higher, or a second treatment delivered more than 6 months after
      RP. Biopsy tumor volume (number and percent positive sites), location of disease
      (anatomical site, laterality), and contiguity of positive biopsies were entered
      into Cox proportional hazards models to predict risk of disease recurrence while
      controlling for Gleason grade, PSA and T stage. RESULTS: Higher number and
      percent of positive biopsy cores were associated with prostate cancer recurrence,
      risk stratification category and Gleason grade, p <0.0001, HR 1.09 (CI 1.02 to
      1.16) and 1.01 (CI 1.00 to 1.01), respectively. Number of biopsy cores taken,
      laterality, contiguity and positive biopsy location were not associated with
      disease recurrence. CONCLUSIONS: The number and the percentage of biopsies
      positive for cancer correlated with treatment failure after radical
      prostatectomy. Contiguity, laterality and location were not associated with
      recurrence.

PMID- 16406889
TI  - Testosterone loss and estradiol administration modify memory in men.
AB  - PURPOSE: Little is known about the effect of androgen deprivation therapy on the
      brain despite the fact that sex steroid receptors are abundant in cortical brain
      regions that mediate memory and other cognitive functions. We characterized the
      impact of androgen deprivation and of subsequent estradiol therapy on the long
      term and working memory of patients with prostate cancer. MATERIALS AND METHODS:
      Long-term memory (immediate and delayed paragraph recall tests), working memory
      (SOP and Trails tests) and Profile of Mood States were assessed at baseline and 4
      weeks later in 18 patients with androgen independent prostate cancer beginning
      second line hormonal therapy with transdermal estradiol 0.6 mg/24 hours. The same
      assessments were performed in 2 age matched control groups of 18 patients with
      prostate cancer undergoing androgen deprivation continuing on hormonal therapy
      and 17 community dwelling healthy men. RESULTS: Immediate and delayed verbal
      memory were significantly worse in patients with prostate cancer on androgen
      deprivation than in age matched healthy controls. In addition, men with prostate
      cancer took more time to complete the Trails A task, indicating slower processing
      speed, but did not differ significantly from healthy controls in working memory
      tasks. In individual repeated measures analyses, verbal memory performance
      improved with estradiol therapy but did not change in the 2 control groups.
      CONCLUSIONS: Sex steroid loss and replacement have effects on specific cognitive
      processes in older men. Furthermore, estrogen has the potential to reverse the
      neurotoxic effects on memory performance caused by androgen deprivation.

PMID- 16406890
TI  - Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy
      for prostate cancer.
AB  - PURPOSE: We assessed the relationship between GnRH agonists and the risk of
      clinical fractures in men with prostate cancer. MATERIALS AND METHODS: Using a
      database of medical claims from 16 large American companies we identified a study
      group of 3,779 men with prostate cancer who received treatment with a GnRH
      agonist and a control group of 8,341 with prostate cancer who were not treated
      with a GnRH agonist. Men with 1 or more medical claims for bone metastases were
      excluded. The rates of any clinical fracture, hip fracture and vertebral fracture
      were compared between the groups. RESULTS: The rate of any fracture was 7.91/100
      vs 6.55/100 person-years at risk in men who received vs did not receive a GnRH
      agonist (relative risk 1.21, 95% CI 1.09 to 1.34). The rates of hip fracture
      (relative risk 1.76, 95% CI 1.33 to 2.33) and vertebral fracture (relative risk
      1.18, 95% CI 0.94 to 1.48) were also higher in men who received a GnRH agonist.
      GnRH agonist treatment was independently associated with fracture risk on
      multivariate analyses. CONCLUSIONS: GnRH agonists increase the risk of clinical
      fracture in men with prostate cancer.

PMID- 16406892
TI  - Prostate specific antigen recurrence rates are low after radical retropubic
      prostatectomy and positive margins.
AB  - PURPOSE: Treatment in patients with a positive surgical margin after radical
      retropubic prostatectomy is controversial. Options are observation, radiation
      therapy and early hormone therapy. Making the appropriate choice should be based
      on an understanding of the risk of recurrence without treatment. MATERIALS AND
      METHODS: We reviewed the records of 1,383 patients after radical retropubic
      prostatectomy was performed by a single surgeon. All specimens were analyzed by a
      single pathologist. Of the patients 936 met criteria for analysis. RESULTS: Mean
      followup in these 936 patients was 45.8 months (minimum 12). The overall PSA
      biochemical recurrence rate was 11.5% (108 of 936 cases). Of the 936 patients 350
      (37%) had tumor at an inked margin. These patients had a recurrence rate of 19%
      (67 of 350), while patients with negative margins had a recurrence rate of 7% (41
      of 586). This difference was statistically significant (p <0.01). Multivariate HR
      analysis revealed that significant risk factors for recurrence in the 936
      patients were PSA greater than 20 ng/ml, clinical stage T2 or greater, Gleason 7
      or greater, seminal vesicle involvement, extraprostatic extension, a visual
      estimate of prostate cancer volume of greater than 9.1% and positive surgical
      margins. Statistically significant risk factors for recurrence in patients with a
      positive margin on multivariate HR analysis were PSA greater than 20 ng/ml,
      Gleason score 7 or greater and seminal vesicle involvement. CONCLUSIONS: Although
      the positive margin rate in this series was 37%, the recurrence rate in these
      patients was only 19%. It is important to consider other factors, such as PSA,
      Gleason score, seminal vesicle involvement and extraprostatic extension, when
      making treatment decisions.

PMID- 16406894
TI  - Postoperative blood loss predicts the development of urinary extravasation on
      cystogram following radical retropubic prostatectomy.
AB  - PURPOSE: We determined if the degree of postoperative bleeding predicts the
      extent of urinary extravasation on initial postoperative cystogram. MATERIALS AND
      METHODS: Between October 2000 to June 2004, 879 men underwent radical retropubic
      prostatectomy performed by a single surgeon. Of these men 97% underwent the
      initial postoperative cystogram 3 to 8 days following radical prostatectomy.
      Postoperative bleeding was expressed as the absolute change in hematocrit between
      hematocrit values measured immediately upon arrival into the recovery room and
      hospital discharge. Three hematocrit points were added to the change in
      postoperative hematocrit for every unit of blood transfused postoperatively. The
      relationship between the change in postoperative hematocrit and the extent of
      extravasation was examined. RESULTS: None, mild, moderate and marked
      extravasation was observed on the initial cystogram in 82.7%, 7.9%, 8.8% and 0.6%
      of cases, respectively. A significant relationship was observed between changes
      in postoperative hematocrit and the extent of extravasation on initial
      cystography (p <0.001). Postoperative changes in absolute hematocrit points of
      less than 2, 2 to 6 and greater than 6 identified clinically meaningful risk
      groups for urinary extravasation. The degree of extravasation was not
      significantly related to risk of anastomotic stricture or urinary incontinence.
      CONCLUSIONS: The extent of postoperative bleeding predicts the extent of urinary
      extravasation on initial cystography. It may be a useful measurement for
      identifying men who can safely undergo early catheter removal without
      cystography.

PMID- 16406896
TI  - A novel single step percutaneous access sheath: the initial human experience.
AB  - PURPOSE: A novel 1-step percutaneous access sheath NS has been developed that
      allows the insertion of a dilating balloon and renal access sheath in a single
      step. We present the initial human experience with this sheath. MATERIALS AND
      METHODS: We performed a retrospective chart and database review of the initial 30
      consecutive patients undergoing percutaneous nephrostolithotomy using the NS.
      Data collected included patient demographics, operative and recovery parameters,
      and complications. RESULTS: Mean patient age was 50.4 years (range 11 to 81),
      mean body mass index was 31.63 kg/m(2) (range 17.1 to 65) and mean preoperative
      stone area was 6.23 cm(2) (range 1 to 14.6). Six and 3 patients had full and
      partial staghorn calculi, respectively. Access was achieved via the upper pole in
      16 patients, middle pole in 7 and lower pole in 7. Mean operative time was 114.8
      minutes (range 61 to 237). Mean estimated blood loss was 145.5 cc (range 10 to
      500) and mean postoperative hospital stay was 4.89 days (range 2 to 14). A total
      of 23 patients (76.7%) had no residual calculi on postoperative computerized
      tomography, 5 (16.7%) had residual fragments 4 mm or less and 2 (6.7%) had
      residual stone fragments greater than 4 mm. There were no complications related
      to the NS. CONCLUSIONS: The NS is safe, easy to use and has potential advantages
      compared to currently available renal access sheaths.

PMID- 16406897
TI  - Intraoperative fragment detection during percutaneous nephrolithotomy: evaluation
      of high magnification rotational fluoroscopy combined with aggressive
      nephroscopy.
AB  - PURPOSE: Percutaneous nephrolithotomy effectively treats large volume renal
      calculi but relies on postoperative imaging to judge success. We evaluated the
      effectiveness of maximizing intraoperative imaging through combined high
      resolution fluoroscopy and flexible nephroscopy. MATERIALS AND METHODS:
      Percutaneous nephrolithotomy was performed cooperatively with a radiologist in an
      interventional radiology suite equipped with a ceiling mounted, high resolution C
      arm. Aggressive rigid and flexible nephroscopy was performed. At the conclusion
      patients were prospectively classified as radiologically and/or endoscopically
      stone-free. Postoperative noncontrast CT allowed fragment classification as stone
      free, 2 mm or less, 2 to 4 mm and greater than 4 mm. RESULTS: The average stone
      dimension +/- SEM was 579 +/- 77 mm(2) in 25 consecutive renal units. CT
      demonstrated that 15 renal units (60%) were stone-free after the primary
      procedure, while 2 (8%), 5 (20%) and 3 (12%) had fragments 2 or less, 2 to 4 and
      greater than 4 mm, respectively. Of 21 renal units considered endoscopically and
      fluoroscopically stone-free postoperative CT demonstrated that 6 had residual
      fragments, of which all were less than 4 mm. All 4 renal units not considered
      radiologically and endoscopically stone-free had fragments on CT. Intraoperative
      fluoroscopy after nephroscopy demonstrated fragments in 36% of renal units, of
      which after further nephroscopy 78% were stone-free on CT. The sensitivity of
      intraoperative imaging with reference to the gold standard of postoperative CT
      was 40%, 38% and 100% at thresholds of 0, 2 and 4 mm, respectively. Specificity
      was 100%, 94% and 95%, respectively. CONCLUSIONS: Flexible nephroscopy combined
      with high magnification rotational fluoroscopy allows sensitive and specific
      intraoperative detection of residual fragments, enabling immediate removal or the
      planning of necessary second look nephroscopy.

PMID- 16406899
TI  - Serum laboratory values following uncomplicated laparoscopic urological surgery.
AB  - PURPOSE: Presentation of complications following laparoscopic surgery can be
      different from corresponding open surgical complications. While leukopenia has
      been identified as a common finding in patients with unrecognized bowel injury
      following laparoscopy, to our knowledge no study has determined if leukopenia or
      other serum abnormalities are unique to patients with laparoscopic complications.
      We present an analysis of postoperative laboratory values from patients after
      uncomplicated urological laparoscopic surgery. MATERIALS AND METHODS: A
      retrospective review of 50 adult patients who had previously undergone
      uncomplicated laparoscopic urological procedures was performed. Exclusion
      criteria were preexisting hematological, immune, liver or pancreatic disorders.
      Common serum laboratory values were measured on postoperative day 1. RESULTS: All
      values for bilirubin were within normal limits. Of patients undergoing a right
      side renal procedure, 10 of 16 (63%) had a postoperative increase in liver
      function tests. Amylase or lipase was increased in a total of 12 (24%) patients.
      Patients undergoing laparoscopic prostatectomy accounted for the majority of this
      group with 9 of 21 (43%) patients having increased amylase or lipase. Finally,
      there were no patients with immediate postoperative leukopenia. CONCLUSIONS:
      Following uncomplicated laparoscopic procedures, bilirubin levels are rarely
      affected, amylase and lipase may be acutely increased following laparoscopic
      prostatectomy, and white blood count is commonly increased. While 16 (36%)
      patients had postoperative leukocytosis, leukopenia was not detected after
      uncomplicated laparoscopic urological surgery and should alert the surgeon to the
      possibility of an undiagnosed complication.

PMID- 16406900
TI  - Testicular fixation following torsion of the spermatic cord--does it guarantee
      prevention of recurrent torsion events?
AB  - PURPOSE: Patients with history of testicular torsion who have undergone
      orchiopexy may rarely present with acute scrotum due to recurrent episodes of
      torsion. Most of the reports in the literature regarding this scenario refer to
      the era when absorbable sutures were used for testicular fixation. Herein, we
      review our experience in recent years, focusing upon the surgical technique and
      sutures' material. MATERIALS AND METHODS: Between 1991 and 2003, 179 patients
      were operated on at our institute with the clinical diagnosis of unilateral
      testicular torsion. They ranged in age between neonates to 45 years old (average
      age 18). In a comprehensive retrospective study we managed to locate 8 patients
      who experienced recurrent intravaginal testicular torsion following previous
      fixation performed in our institute. RESULTS: The patients who experienced repeat
      torsion have initially presented at the mean age of 18.5 years old (range 12 to
      30) with unilateral twisted testicle (left 3, right 5). Urgent explorations were
      generally performed, apart from in 2 cases that underwent spontaneous detorsion
      which was followed by an elective surgery. Testicular fixation was conducted by
      suturing of the tunica albuginea to the dartos layer by 2 sutures at each side,
      using chromic 3-zero in the 3 more early cases, followed by the usage of
      polyglactin 3-zero stitches in 4 subsequent cases and 3 sutures of polypropylene
      4-zero for each testicle, thereafter, in the most recent case. The patients
      presented with repeat torsion, 0.5 to 23 years subsequently (average 7 years),
      involving either the ipsilateral testicle in 4 cases or the contralateral gonad
      in 4. CONCLUSIONS: Recurrent torsion following previous testicular fixation may
      appear many years following the primary procedure, even in cases in which either
      polyglactin or, notwithstanding, polypropylene sutures have been applied, in
      accordance with the common practice used in the last 2 decades. Increased
      awareness regarding this possibility is imperative for early diagnosis and
      prevention of testicular loss.

PMID- 16406902
TI  - Use of ultrasonography for the diagnosis of testicular injuries in blunt scrotal
      trauma.
AB  - PURPOSE: We determined the use of scrotal ultrasonography in the initial
      diagnosis and management of testicular injuries due to blunt scrotal trauma.
      MATERIALS AND METHODS: We performed a retrospective review of 65 patients
      presenting to our Emergency Department with blunt scrotal trauma in the last 25
      years. In 47 patients an inconclusive clinical examination prompted scrotal
      ultrasonography. A heterogeneous echo pattern of the testicular parenchyma with
      loss of contour definition was the basis for diagnosis of testicular rupture. The
      sensitivity and specificity of scrotal ultrasonography were determined by
      comparing this radiographic criterion with definitive intraoperative findings and
      the need for delayed orchiectomy due to undiagnosed testicular rupture. RESULTS:
      Of the 65 patients sustaining blunt scrotal trauma 44 (68%) underwent scrotal
      exploration, and 30 (46%) of these injuries involved rupture of the tunica
      albuginea. Among the 47 scrotal ultrasounds performed to supplement a
      nondiagnostic clinic examination, there were 32 suspected testicular ruptures.
      Thus, the 2 false-positives resulted in a specificity of 93.5% in those patients
      explored. No delayed orchiectomies were performed for missed testicular ruptures,
      resulting in 100% sensitivity. The majority of testicular ruptures were salvaged
      (83%), with only 5 of the 30 (17%) requiring orchiectomy (4 of these patients had
      delayed presentation greater than 48 hours). CONCLUSIONS: Scrotal
      ultrasonography, with the single radiographic finding of a heterogeneous echo
      pattern of the testicular parenchyma with loss of contour definition, is highly
      sensitive and specific in the diagnosis of testicular rupture in an otherwise
      equivocal scrotal examination. Accurate diagnosis and prompt repair led to a
      salvage rate for testicular rupture specifically of 83% and overall of 92%, with
      preservation of the testicular parenchyma and hormonal function, and avoidance of
      the delayed complications of chronic pain, atrophy and orchiectomy associated
      with missed testicular rupture.

PMID- 16406903
TI  - The use of bowel for ureteral replacement for complex ureteral reconstruction:
      long-term results.
AB  - PURPOSE: Ileal and intestinal ureteral replacement remains a useful procedure for
      complex ureteral reconstruction. We examined the long-term safety and efficacy of
      this procedure, especially in regard to maintaining preoperative renal function
      and the avoidance of major complications. MATERIALS AND METHODS: A total of 56
      patients underwent intestinal ureteral substitution at our institution between
      1979 and 2003, including 52 with an ileal ureteral replacement, 2 with colonic
      replacement alone and 2 with bilateral ureteral replacement, necessitating ileum
      and colon for 1 ureter each. The factors reviewed were indications for surgery,
      type of ureteral replacement, and the presence and type of complications.
      Followup data included excretory urogram or equivalent imaging results, and
      measurement of serum chloride, bicarbonate and creatinine before and after the
      procedure. RESULTS: Overall the complication rate remained low. Mean followup was
      6.04 years (median 3.2). Most postoperative complications, which occurred in 10
      patients (17.9%), were minor in nature, including pyelonephritis, fever of
      unknown origin, neuroma, hernia, recurrent urolithiasis and deep venous
      thrombosis. Major complications occurred in 6 patients (10.5%), including
      anastomotic stricture, ileal graft obstruction, wound dehiscence and chronic
      renal failure. Overall patients did not experience worsening renal function after
      the procedure with equivalent median creatinine before and after the procedure
      (1.0 mg/dl). CONCLUSIONS: During long-term followup major complications are rare
      and renal function remains preserved. Ileal and intestinal ureteral substitution
      remains a safe and efficacious procedure in patients with complex and difficult
      ureteral issues not amenable to more conservative measures.

PMID- 16406905
TI  - Changes in the upper urinary tract after radical cystectomy and urinary
      diversion: a comparison of antirefluxing and refluxing orthotopic bladder
      substitutes and the ileal conduit.
AB  - PURPOSE: We evaluated and compared the effects of different types of urinary
      diversion on functional and radiographic changes in the upper urinary tract.
      MATERIALS AND METHODS: We analyzed data on 275 patients who underwent radical
      cystectomy and urinary diversion for bladder cancer and were observed at least 12
      months. Of the patients 197 received an orthotopic bladder substitute, including
      antirefluxing ureteral anastomoses in 111 (group 1) and refluxing ureteral
      anastomoses in 86 (group 2). Ileal conduits were created in 78 patients (group
      3). Serial serum Cr, radiographic changes in the upper urinary tract after
      diversion and the number of episodes of APN were compared by diversion method.
      Mean followup was 52 months (range 12 to 174 months) with no difference among the
      groups. RESULTS: Compared with group 3 patients in groups 1 and 2 demonstrated a
      significantly higher incidence of moderate to severe hydronephrosis (p = 0.001)
      but the incidence was similar between groups 1 and 2 (6.3%, 8.3% and 1.4% of the
      renal units in groups 1 to 3, respectively). Stabilized postoperative Cr did not
      differ among the groups. CRF, defined as Cr 3.0 mg/dl or greater, occurred in
      2.7% of the patients in group 1 and in 3.5% of those in group 2 but in none in
      group 3. APN was noted in 3.3%, 4.4% and 0.4% of patients in groups 1 to 3,
      respectively (p = 0.012). CONCLUSIONS: An ileal conduit with a lower rate of
      diversion related hydronephrosis, CRF and morbidity associated with APN was
      superior to orthotopic bladder substitutes. Between the refluxing and
      antirefluxing types of orthotopic bladder substitutes no significant difference
      in functional or radiographic changes was noted.

PMID- 16406907
TI  - Is the bladder a reliable witness for predicting detrusor overactivity?
AB  - PURPOSE: We determined how well the symptoms of OAB syndrome correlate with
      urodynamic DO using International Continence Society definitions. MATERIALS AND
      METHODS: The study included adult males and females 18 years or older who
      attended a tertiary referral center for urodynamics from February 2002 to
      February 2004. Patients were selected based on OAB syndrome symptoms (urgency,
      urgency urinary incontinence and frequency). The percent of patients who had
      symptoms alone or in combination and DO was calculated. RESULTS: There was a
      better correlation in results between OAB symptoms and the urodynamic diagnosis
      of DO in men than in women. Of men 69% and 44% of women with urgency (OAB dry)
      had DO, while 90% of men and 58% of women with urgency and urgency urinary
      incontinence (OAB wet) had DO. Stress urinary incontinence seems to have
      accounted for the decreased rates in women since 87% of women with urgency
      urinary incontinence also had the symptom of stress urinary incontinence. The ICS
      definition does not specify what constitutes abnormal voiding frequency. Analysis
      of results showed that increasing voiding frequency did not have any effect on
      increasing the accuracy of diagnosis of DO except in women with 10 or more
      daytime micturition episodes. CONCLUSIONS: The bladder is a better and more
      reliable witness in men than in women with a greater correlation between OAB
      symptoms and urodynamic DO, more so in the OAB wet than in OAB dry patients.

PMID- 16406909
TI  - Preoperative biofeedback assisted behavioral training to decrease post
      prostatectomy incontinence: a randomized, controlled trial.
AB  - PURPOSE: We tested the effectiveness of preoperative biofeedback assisted
      behavioral training for decreasing the duration and severity of incontinence, and
      improving quality of life in the 6 months following radical prostatectomy.
      MATERIALS AND METHODS: We performed a prospective, randomized, controlled trial
      comparing preoperative behavioral training to usual care. The volunteer sample
      included 125 men 53 to 68 years old who elected radical prostatectomy for
      prostate cancer. Patients were stratified according to age and tumor
      differentiation, and randomized to 1 preoperative session of biofeedback assisted
      behavioral training plus daily home exercise or a usual care control condition,
      consisting of simple postoperative instructions to interrupt the urinary stream.
      The main outcome measurements were duration of incontinence (time to continence),
      as derived from bladder diaries, incontinence severity (the proportion with
      severe/continual leakage), pad use, Incontinence Impact Questionnaire,
      psychological distress (Hopkins Symptom Checklist) and health related quality of
      life (Medical Outcomes Study Short Form Health Survey). RESULTS: Preoperative
      behavioral training significantly decreased time to continence (p = 0.03) and the
      proportion of patients with severe/continual leakage at the 6-month end point
      (5.9% vs 19.6%, p = 0.04). There were also significant differences between the
      groups for self-reported urine loss with coughing (22.0% vs 51.1%, p = 0.003),
      sneezing (26.0% vs 48.9%, p = 0.02) and getting up from lying down (14.0% vs
      31.9%, p = 0.04). No differences were found on return to work and usual
      activities or quality of life measures. CONCLUSIONS: Preoperative behavioral
      training can hasten the recovery of urine control and decrease the severity of
      incontinence following radical prostatectomy.

PMID- 16406911
TI  - Central acute D2 stimulation worsens bladder function in patients with mild
      Parkinson's disease.
AB  - PURPOSE: The different roles of D1 and D2 dopamine receptors in LUT behavior have
      been demonstrated in animal studies. In particular D2 selective agonists and D1
      selective antagonists seem to produce a reduction of the bladder capacity in
      conscious rats. This finding has never been confirmed in human studies. Thus, in
      this study we investigated the role of D1 and D2 agonists/antagonists on LUT
      behavior in patients with PD. MATERIALS AND METHODS: A total of 87 patients with
      mild PD were evaluated. Patients were evaluated with urodynamic studies
      (cystometry followed by a pressure flow study with perineal floor
      electromyography) performed in off status and after oral administration of 250 mg
      of LD. In 70 patients a third urodynamic evaluation was conducted in one of the
      following conditions: after simultaneous administration of 250 mg oral LD and 60
      or 120 mg oral domperidone (D2 peripheral antagonist); after simultaneous
      administration of 250 mg oral LD and 25, 50 or 150 mg intramuscular L-sulpiride
      (D2 central and peripheral antagonist). Several urodynamic parameters were
      evaluated and results obtained in different conditions compared. RESULTS: LD
      alone worsened detrusor overactivity: in particular, a reduction of first urinary
      sensation, involuntary detrusor contraction threshold (reflex volume) and bladder
      capacity was observed. L-sulpiride (central and peripheral D2 antagonist)
      coadministration counteracted the worsening in a dose dependent manner.
      Domperidone (peripheral D2 antagonist) coadministration failed to determine the
      same counteraction. CONCLUSIONS: According to our results, a central acute D2
      stimulation seems to be responsible of a reduction of bladder capacity with
      worsening of detrusor overactivity in patients with mild PD.

PMID- 16406913
TI  - A multicenter evaluation of urinary incontinence management and outcome in spina
      bifida.
AB  - PURPOSE: We describe urinary continence management and outcome in patients with
      spina bifida to identify the procedures that are most successful. MATERIALS AND
      METHODS: In a multicenter retrospective cohort study medical charts were studied.
      At the same time in a cross-sectional survey sociodemographic characteristics,
      orthopedic features and urinary continence were described based on the frequency
      of leakage from the viewpoint of patients or close relatives using a Likert scale
      of 5 items, namely 1-leakage permanent to 5-leakage never. RESULTS: A total of
      421 patients were included, of whom 191 (45%) had been medically treated with a
      normal voiding pattern according to the patient viewpoint in 21%, clean
      intermittent catheterization in 61% and no specific bladder emptying method in
      18%. The mean leakage score +/- SD was 2.74 +/- 1.55. On the other hand, 230
      patients (55%) were surgically treated. Except for 23 patients who underwent
      noncontinent urinary diversion 207 were considered for treatment and continence
      description. The mean leakage score was 3.45 +/- 1.60. An artificial urinary
      sphincter in male and females, and a sling or Kropp technique in females were
      satisfactory when bladder enlargement was not required. In cases of bladder
      augmentation without continent diversion an artificial urinary sphincter in males
      and a bladder neck sling or cinch, Kropp and Young-Dees procedures in females
      have provided the best results. In cases of bladder enlargement with continent
      urinary diversion bladder neck closure or a wrap have provided the best results
      whatever the patient sex. CONCLUSIONS: Many factors may influence the choice of a
      technique, such as patient sex, bladder characteristics or orthopedic conditions.
      However, since to our knowledge no randomized, controlled study has been yet
      performed, definitive conclusions on the best way to achieve urinary continence
      in patients with spina bifida cannot be established.

PMID- 16406914
TI  - Post-void residual urine volume is not a good predictor of the need for invasive
      therapy among patients with benign prostatic hyperplasia.
AB  - PURPOSE: We assessed the value of baseline PVR as predictor of the need for
      invasive therapy during long-term followup of patients with clinical BPH treated
      initially with alpha1-blockers or WW. MATERIALS AND METHODS: The records of a
      cohort of 942 patients with BPH treated with alpha(1)-blockers or WW were
      reviewed. Baseline I-PSS scores, PSA, prostate volume, uroflowmetry, pressure
      flow parameters and followup data were collected prospectively. Correlations
      between PVR and other baseline parameters were calculated. The 5-year cumulative
      risks of invasive therapy were calculated with the Kaplan-Meier method. After
      stratification of PVR by various cutoff levels (50, 100 and 300 ml), rate ratios
      between large and small PVRs were calculated using proportional hazards analyses.
      RESULTS: PVR has weak (-0.2<R <0.2) correlations with other baseline parameters.
      With increasing PVR cutoff levels, the 5-year cumulative risk of invasive therapy
      for the large PVR subgroup, increases from 45% to 64% and from 15% to 21% in the
      alpha1-blockers and WW group, respectively. Large PVR yields a significant 2-fold
      up to a 4-fold increased risk of invasive therapy compared to small PVR in both
      treatment groups. In multivariate models these significant risk differences
      largely disappear, although a statistically not significant higher risk remains
      for the large PVR (greater than 300 ml) patients. CONCLUSIONS: In general,
      baseline PVR has little prognostic value for the risk of BPH related invasive
      therapy in patients on alpha1-blocker and WW. Only patients with large PVR have a
      2-fold increased risk of invasive therapy compared to patients with smaller PVR.

PMID- 16406917
TI  - Hand assisted retroperitoneoscopic living donor nephrectomy in elderly donors.
AB  - PURPOSE: We assessed the influence of HARDN on residual donor kidney and
      allograft function, invasiveness and morbidity in elderly living donors.
      MATERIALS AND METHODS: A total of 89 living donors underwent nephrectomy before
      September 2004 at our institution. The 18 donors who were 65 years or older
      included 4 of 27 with ODN and 14 of 62 with HARDN. RESULTS: In older (65 years or
      older) donors mean operative time, mean blood loss and warm ischemia time in the
      HARDN group did not differ from those in the ODN group. None of the donors had
      major complications. Older donors with HARDN had a tendency toward a shorter
      hospital stay than those with ODN. Postoperative serum creatinine in older donors
      with HARDN was higher than that in younger donors with HARDN, while there was no
      difference in postoperative serum creatinine between older donors with HARDN and
      those with ODN. The frequency of allograft losses tended to be higher in older
      than in younger kidneys (4 of 18 vs 5 of 71, p = 0.054). However, most allograft
      losses did not seem to be related to surgical technique. CONCLUSIONS: Although
      further studies, especially with long-term followup, are necessary, HARDN is
      suggested to be safe and minimally invasive surgery even in elderly donors and to
      be comparable to open surgery in terms of morbidity, the residual donor kidney
      and allograft function.

PMID- 16406915
TI  - Combination therapy with doxazosin and finasteride for benign prostatic
      hyperplasia in patients with lower urinary tract symptoms and a baseline total
      prostate volume of 25 ml or greater.
AB  - PURPOSE: We examined data from the Medical Therapy of Prostatic Symptoms trial to
      determine the relationship between baseline TPV and the effect of medical therapy
      in men with LUTS secondary to BPH. MATERIALS AND METHODS: A total of 3,047
      patients with LUTS were randomized to placebo, 4 to 8 mg doxazosin, 5 mg
      finasteride or the combination of doxazosin and finasteride. Average treatment
      duration was 4.5 years The primary outcome was time to overall clinical
      progression of BPH, defined as a confirmed 4 point or greater increase in AUA SS,
      acute urinary retention, incontinence, renal insufficiency or recurrent urinary
      tract infection. Secondary outcomes were the need for invasive therapy for BPH,
      and changes in AUA SS and the maximum urinary flow rate with time. TPV was
      measured by transrectal ultrasound at baseline and study end. RESULTS: In
      patients with a small prostate (baseline TPV less than 25 ml) combination therapy
      was no better than doxazosin alone for decreasing the risk of clinical
      progression of BPH and need for invasive therapy as well as improving AUA SS and
      the maximum urinary flow rate. However, in patients with moderate size (25 to
      less than 40 ml) or enlarged (40 ml or greater) glands combination therapy led to
      a clinical benefit in these outcomes that was superior to that of doxazosin or
      finasteride. CONCLUSIONS: Combination therapy with doxazosin and finasteride led
      to a greater decrease in the risk of clinical progression of BPH than either drug
      alone in patients with LUTS with a baseline TPV of 25 ml or greater.

PMID- 16406919
TI  - Factors affecting the loss of length associated with tunica albuginea plication
      for correction of penile curvature.
AB  - PURPOSE: Loss of length is a common postoperative complaint of the patient who
      undergoes surgical correction of penile curvature. We investigate the factors
      influencing complications in patients who have undergone TAP for PD and chordee.
      MATERIALS AND METHODS: A total of 102 patients underwent TAP for PD (68) or
      chordee (34) between 1997 and 2004. Data were gathered on each patient's
      preoperative complaints, physical examination, Doppler ultrasound, operative data
      and postoperative complaints. For the purposes of this study penile length was
      measured from pubis to corona along the dorsal surface of the stretched phallus.
      RESULTS: Mean ages at surgery for men with PD and chordee were 53 and 24,
      respectively. A range of 1 to 6 plications were performed on each patient (mean
      3) with an acceptably straight penis (curve less than 20 degrees) being achieved
      in 99% of patients. Mean followup for our patient population was 29 months and
      revealed only 1 patient with residual curvature. The mean loss in length after
      TAP was 0.36 +/- 0.5 cm with a range of 0 to 2.5 cm. When calculated as a percent
      of length lost from preoperative length, the postoperative percent length lost
      was 2.4%. When stratified into groups based on direction of curvature, the
      patients with ventral or ventrolateral curve had the highest percent loss of
      length. A 1-way ANOVA of these groups proved the differences between each group
      to be statistically significant (p = 0.04). Length change also significantly
      correlated with preoperative stretched penile length and the severity of
      curvature as measured in degrees in the operating room at time of surgery.
      Parameters that did not demonstrate a statistically significant impact on penile
      shortening included patient age, number of plications performed, plaque size, and
      hinge/narrowing effect due to a PD plaque. CONCLUSIONS: The TAP procedure is a
      safe and effective means of correcting penile curvature, with similar overall
      outcomes between patients with PD and chordee. Shortening of the penis does
      commonly occur but is dependent on direction and degree of curvature, as well as
      the length of the phallus.

PMID- 16406920
TI  - A stable isotope-mass spectrometric method for measuring human spermatogenesis
      kinetics in vivo.
AB  - PURPOSE: Currently it is thought to take 60 to 70 days to produce and ejaculate
      human sperm. This estimate is derived mainly from a single older, descriptive,
      kinetic analysis of spermatogenesis. We developed a noninvasive method to assess
      germ cell turnover time accurately in vivo using stable isotope labeling and gas
      chromatography/mass spectrometry analyses. We confirmed the postulated length of
      a normal cycle of spermatogenesis. MATERIALS AND METHODS: A total of 11 men with
      normal sperm concentrations ingested (2)H(2)O daily for 3 weeks. Semen samples
      were collected every 2 weeks for up to 90 days. Label incorporation into sperm
      DNA was quantified by gas chromatography/mass spectrometry, allowing calculation
      of the percent of new cells present. A cycle of sperm production was determined
      as the lag time until labeled sperm appeared in the ejaculate. RESULTS: Labeled
      sperm were detected after a mean +/- SD of 64 +/- 8 days (range 42 to 76). In 1
      subject the time lag was 42 days but it was at least 60 in all other subjects. In
      most subjects plateau labeling in sperm was not attained. In 2 subjects the rise
      and fall of the labeling curve was steep and reached greater than 85% new cells,
      suggesting rapid washout of old sperm in the epididymal reservoir. CONCLUSIONS:
      This direct kinetic assessment confirms a course of spermatogenesis that is on
      the shorter side of traditional estimates based on prior analyses. In addition,
      the variability observed in healthy men suggests that characteristics such as the
      epididymal reservoir effect may influence the modeling of in vivo
      spermatogenesis.

PMID- 16406922
TI  - Multi-institutional validation of vasectomy reversal predictor.
AB  - PURPOSE: Some urologists who perform vasectomy reversals are not experienced with
      performing VE. A model to preoperatively identify patients who may require
      referral to an experienced VE surgeon was created (). We tested the model at
      multiple institutions. MATERIALS AND METHODS: The model had previously been
      designed in 483 patients who underwent vasectomy reversal at 1 institution (100%
      sensitive and 59% specific for predicting the need for VE). It was based on time
      since vasectomy and patient age. We tested it prospectively in 33 patients and
      retrospectively in a total of 312 at 6 other institutions. The predictive
      accuracy of the model was compared to using a simple duration from vasectomy
      cutoff alone, as is used in clinical practice. RESULTS: The model had 84%
      sensitivity and 58% specificity for detecting the need for VE in a total of 345
      patients at 7 institutions. If using only a duration from vasectomy cutoff of 10
      years to predict the need for VE, sensitivity was only 69%. At a cutoff of 4
      years sensitivity was 99% but specificity was only 23%. Thus, the model performed
      better than any specific duration cutoff alone. CONCLUSIONS: The predictive model
      provides 84% sensitivity for detecting patients who may require VE during
      vasectomy reversal across 7 institutions (58% specificity). The model more
      accurately predicts the need for VE than using a specific duration from vasectomy
      cutoff alone.

PMID- 16406923
TI  - Differences in prevalence of urinary incontinence by race/ethnicity.
AB  - PURPOSE: We compared the prevalence of urinary incontinence by type among white,
      black, Hispanic and Asian-American women. MATERIALS AND METHODS: The RRISK is a
      population based cohort study of 2,109 randomly selected middle-aged and older
      women. Incontinence and other variables were assessed by self-report
      questionnaires and in person interviews. Labor and delivery and surgical data
      were abstracted from medical records archived since 1946. Logistic regression was
      used to estimate the OR with 95% CIs for incontinence while adjusting for
      covariates. RESULTS: The age adjusted prevalence of weekly incontinence was
      highest among Hispanic women, followed by white, black and Asian-American women
      (36%, 30%, 25% and 19%, respectively, p <0.001). Type of incontinence also
      differed among groups, with weekly stress incontinence prevalence being 18%, 15%,
      8% and 8% (p <0.001), and weekly urge incontinence prevalence being 10%, 9%, 14%
      and 7% (p <0.001). After adjustment for age, parity, hysterectomy, estrogen use,
      body mass, menopausal status and diabetes, the risk of stress incontinence
      remained significantly lower in black (adjusted OR 0.36, 95% CI 0.23-0.57) and
      Asian-American (adjusted OR 0.54, 95% CI 0.34-0.86) women compared to white
      women. In contrast, the risk of urge incontinence was similar in black (adjusted
      OR 1.19, 95% CI 0.79-1.81) and Asian-American (adjusted OR 0.86, 95% CI 0.52
      1.43) women compared to white women. CONCLUSIONS: Significant differences in the
      adjusted risk of stress incontinence among Hispanic, white, black and Asian
      American women suggest the presence of additional, as yet unrecognized, risk or
      protective factors for stress incontinence.

PMID- 16406924
TI  - Pelvicaliceal anatomical variation between stone bearing and normal contralateral
      kidneys--does it have an impact on stone formation in pediatric patients with a
      solitary lower caliceal stone?
AB  - PURPOSE: We aimed to investigate the probable effect of pelvicaliceal anatomical
      differences between stone bearing and normal contralateral kidneys on the
      etiology of stone formation in children with a solitary lower pole caliceal
      stone. MATERIALS AND METHODS: We reviewed the clinical records of 25 pediatric
      patients who underwent SWL for a solitary lower caliceal stone and 15 healthy
      pediatric patients who served as controls. Lower pole IPA, IL and IW, together
      with other caliceal variables obtained from the pelvicaliceal anatomy of the
      stone bearing and contralateral normal kidneys of patients with urolithiasis, and
      both kidneys of the control group were measured based on excretory urography.
      Also, total pelvicaliceal volume for both kidneys was calculated. RESULTS: Mean
      LIPAs of stone bearing kidneys compared to the normal contralateral kidneys was
      more acute, equal and wider in 52%, 16% and 32% of the patients, respectively.
      Mean pelvicaliceal volumes of the stone forming and normal kidneys were 1,553.8
      mm(3) (range 242 to 7,107) and 581.0 mm(3) (90 to 2,662), respectively, and there
      was statistical significance only in pelvicaliceal volumes between the stone
      bearing and contralateral normal kidneys (p <0.001). CONCLUSIONS: Our results
      reveal that IPA, IL and IW of calices do not have an effect on stone formation in
      pediatric patients. However, large pelvicaliceal volume seems to be a significant
      risk factor for stone formation in the lower calix, probably because it creates
      abnormal urodynamic and morphological features, especially when accompanied by
      other metabolic abnormalities.

PMID- 16406926
TI  - A neuroanatomical comparison of humans and spotted hyena, a natural animal model
      for common urogenital sinus: clinical reflections on feminizing genitoplasty.
AB  - PURPOSE: Surgical treatment of the common urogenital sinus phallus has been one
      of the most challenging areas in pediatric urology. To better understand the
      neuroanatomy of the common urogenital sinus phallus, we evaluated an animal model
      naturally having this condition, the spotted hyena, Crocuta crocuta. We compared
      the neuroanatomy of male and female humans and spotted hyenas using anatomical,
      immunohistochemical and 3D reconstruction techniques. We also examined the
      implications of the pattern of clitoral innervation for the unique challenges
      faced by female spotted hyenas, the only extant species of mammal that mates and
      gives birth through the clitoris. MATERIALS AND METHODS: Three adult male and 3
      female spotted hyenas were studied. With the animals under anesthesia gross
      anatomical examination was performed before and after artificial erection.
      Histological analysis was performed on one 95-day fetal male and female spotted
      hyena specimens, and on 18 human male and female fetal external genitalia
      specimens using antibodies raised against the neuronal marker S-100. Three
      dimensional computer reconstruction using serial sections allowed analysis of the
      neuroanatomy of the penis, clitoris and common urogenital sinus of the fetal
      spotted hyena and human. RESULTS: Compared to other mammals, the clitoris and
      penis of spotted hyenas were remarkably similar in size and configuration in the
      flaccid and erect states. Male and female hyenas had a single opening on the tip
      of the glans penis/clitoris. The basic anatomical structures of the corporeal
      bodies in both sexes of humans and spotted hyenas were similar. As in humans, the
      dorsal nerve distribution was unique in being devoid of nerves at the 12 o'clock
      position in the penis and clitoris of the spotted hyena. Dorsal nerves of the
      penis/clitoris in humans and male spotted hyenas tracked along both sides of the
      corporeal body to the corpus spongiosum at the 5 and 7 o'clock positions. The
      dorsal nerves penetrated the corporeal body and distally the glans in the hyena.
      In female hyenas the dorsal nerves fanned out laterally on the clitoral body.
      Glans morphology was different in appearance in both sexes, being wide and blunt
      in the female and tapered in the male. CONCLUSIONS: The neuroanatomy of the male
      and female external genitalia in the spotted hyena, Crocuta crocuta, although
      grossly similar, has distinct anatomical and functional characteristics. The
      clitoris of the spotted hyena is a classic example of a natural animal model of a
      common urogenital sinus. The neuroanatomical characteristics of the spotted hyena
      may be a useful model to simulate the anatomy of common urogenital sinus anomaly
      in humans.

PMID- 16406927
TI  - Rectosigmoid pouch (Mainz Pouch II) in children.
AB  - PURPOSE: Continent anal urinary diversion is a therapeutic option in bladder
      exstrophy. We report our long-term results with the rectosigmoid pouch (Mainz
      pouch II), a modification of the classic ureterosigmoidostomy. MATERIALS AND
      METHODS: A total of 38 children with a mean age of 5 years (range 0.5 to 17)
      underwent a Mainz pouch II procedure between 1991 and 2004. Most patients (33)
      had bladder exstrophy or incontinent epispadias. In 14 children (37%) urinary
      diversion was performed after failed primary reconstruction. In 6 children
      conversion was performed from an incontinent type of urinary diversion. Renal
      function, continence and metabolic changes were analyzed. A total of 35 children
      were followed for a mean of 112 months (range 5 to 147). RESULTS: All children
      were continent during the daytime but 3 (8.6%) suffered from nighttime
      incontinence requiring pads. With respect to the upper urinary tract, 6 children
      (15.8%) had development of pyelonephritis, mostly with stenosis of the
      ureterointestinal anastomosis. Reimplantation of the ureter was required in 10 of
      69 RU (14.5%), of which 7 (10.1%) were due to ureterointestinal stenosis and 3
      (4.3%) were due to reflux. Serum creatinine was within normal limits in all
      children. During followup acid-base balance was monitored, and early alkali
      supplementation was initiated in 24 of 35 children (69%) when the base excess was
      less than -2.5 mmol/l. One child had development of clinical acidosis requiring
      hospitalization. After followup of more than 10 years annual rectosigmoidoscopy
      was performed in 16 children/young adults without pathological findings.
      CONCLUSIONS: The Mainz pouch II procedure for children with genitourinary
      anomalies promises excellent continence rates. However, periodic followup studies
      are important to check the upper urinary tract and prevent metabolic acidosis.
      Due to the risk of malignancy at the ureterointestinal anastomosis, endoscopy
      should be performed annually beginning at postoperative year 10. The Mainz pouch
      II procedure is safe in the long term. Without stoma, appliance or
      catheterization this type of continent urinary diversion is specifically suitable
      for children.

PMID- 16406928
TI  - Results of a 2-year multicenter trial of endoscopic treatment of vesicoureteral
      reflux with synthetic calcium hydroxyapatite.
AB  - PURPOSE: With no FDA approved material available for endoscopic treatment of
      vesicoureteral reflux, in 2001 we began a prospective multicenter trial of
      synthetic calcium hydroxyapatite as a subureteral bulking agent in children with
      traditional indications for surgical repair. MATERIALS AND METHODS: A total of 98
      patients (155 ureters) with grades II to IV reflux were enrolled at 10 sites in
      the United States to obtain 86 patients with completed protocol end points at 3
      months. Of the 86 patients 74 underwent renal and bladder ultrasonography, blood
      count and serum chemistry analysis, and VCUG at 1 year. A total of 46 patients
      (47%) completed 2-year study end points, including VCUG. RESULTS: At 1 and 2
      years 24 of the 74 patients (32%) were cured. Ureteral cure rates were 46% and
      40% at 1 and 2 years, respectively. With 35 patients treated and 85% compliance
      with the required 2-year VCUG the primary center achieved 2-year cure rates of
      66% of patients and 72% of ureters. CONCLUSIONS: Synthetic calcium hydroxyapatite
      is a safe, durable and effective material for endoscopic treatment of VUR.
      Increased experience with the injection of synthetic calcium hydroxyapatite
      yields improved results.

PMID- 16406929
TI  - Neurogenic bladder dysfunction after sacrococcygeal teratoma resection.
AB  - PURPOSE: SCT treatment in newborns consists of surgery and selective
      chemotherapy. Few reports document urological sequelae using this approach. This
      review focuses on the urological and neurourological findings following SCT
      treatment in the newborn period. MATERIALS AND METHODS: We reviewed the records
      of all infants with SCT resected in early infancy who underwent urodynamic
      evaluation for bladder dysfunction between 1986 and 2004. The radiological,
      neurological and urodynamic findings, and postoperative incontinence management
      were analyzed. RESULTS: We analyzed UDS of 14 patients who presented with urinary
      infection or incomplete bladder emptying after SCT resection. At the time of UDS
      an abnormal neurological examination was noted in 5 patients (36%). Detrusor
      overactivity was seen in 8 patients, underactivity in 2 and normal activity in 4.
      Abnormal urethral sphincter EMG potentials were observed in 7 of 13 patients
      (54%). Five of 13 patients (38%) had sphincter dyssynergia during voiding.
      Consequently, CIC was needed in 11 of the 14 patients (79%) to empty the bladder,
      of whom 5 also required anticholinergics to improve detrusor compliance and
      dryness. Only 3 patients voided spontaneously with normal bladder and sphincter
      function, of whom 2 were toilet trained. Hydronephrosis was seen in 6 patients
      and reflux was noted in 7 (including 5 of 6 with hydronephrosis). Antireflux
      surgery was performed in 6 patients, all of whom had up to grade 4 reflux due to
      recurrent urinary tract infection. One girl with grade 2 reflux had spontaneous
      resolution. CONCLUSIONS: SCT and its treatment can produce neurourological
      dysfunction of the lower urinary tract with high grade reflux, and abnormal
      bladder and urethral function. Complete assessment, including urodynamic studies,
      is imperative preoperatively and postoperatively. Constant vigilance is required
      to maintain as near normal bladder function as possible and to prevent upper
      urinary tract injury.

PMID- 16406931
TI  - Lower urinary tract symptoms after renal transplantation in children.
AB  - PURPOSE: We investigated the prevalence and nature of LUTS after renal Tx in
      children. The focus of the study was the presence of LUTS in children without a
      history of urological symptoms. We also studied the relationship between the
      characteristics of these patients and the occurrence of LUTS. MATERIALS AND
      METHODS: Data were gathered using a written questionnaire, frequency volume
      chart, free uroflowmetry, transabdominal ultrasonography and medical records. The
      study group (30 patients) consisted of 9 children (30%) undergoing renal
      transplantation with an underlying urological disease and 21 (70%) with an
      underlying nephrological disease. RESULTS: In the nephrological group the
      incidence of high capacity bladder was 75%, residual urine 50%, UTI 43%,
      hesitancy 38%, intermittent flow 33%, bladder pain 33%, nighttime incontinence
      29%, nocturia 24%, feeling of incomplete emptying 15%, daytime incontinence 14%,
      straining 14%, urgency 10%, burning sensation 10% and intermittency 5%. No
      substantial difference in the occurrence of LUTS, UTI or high bladder capacity
      after Tx was found between children with an underlying urological disease and
      those with an underlying nephrological disease. On average, patients in both
      groups suffered from 3 different LUTS. CONCLUSIONS: After renal Tx children with
      a nephrological disease demonstrated a high incidence of LUTS. The occurrence of
      LUTS combined with UTI and increased bladder capacity indicates that these
      children are at risk for development of myogenic failure. This finding emphasizes
      the importance of close urological followup after Tx in children with urological
      and nephrological disease.

PMID- 16406933
TI  - Serum cystatin C as a reliable marker of changes in glomerular filtration rate in
      children with urinary tract malformations.
AB  - PURPOSE: Cystatin C has been suggested as a simple method of estimating GFR more
      accurately than creatinine in children. We compared the diagnostic accuracy of
      cystatin C with serum creatinine and the Schwartz formula for estimating GFR in
      patients with UTMs. MATERIALS AND METHODS: We prospectively compared 72 patients
      with UTMs (20 days to 36 months old, 58 males and 14 females) with a group of 72
      healthy controls (10 days to 48 months old, 53 males and 19 females). All
      patients underwent nuclear medicine clearance investigations with (99m)Tc DTPA.
      RESULTS: Serum concentration of cystatin C revealed a higher correlation with
      (99m)Tc DTPA (r = 0.62, p <0.001) than serum concentration of creatinine (r =
      0.30, p <0.01) or Schwartz formula (r = 0.51, p <0.001). These results were more
      evident in patients with uropathy (19) with mild renal impairment. Agreement
      between methods was assessed using Bland Altman analysis. Mean differences
      between GFR calculated with (99m)Tc DTPA and cystatin C based GFR estimation or
      Schwartz formula were -2.6% +/- 46.7% and -73.4% +/- 53.6%, respectively.
      Diagnostic accuracy in identifying decreased GFR measured as AUC was always
      highest for cystatin C but hardly sufficient for the 3 variables. Cystatin C
      performed better in the 0 to 6-month-olds (0.70 +/- 0.08 for cystatin C, 0.58 +/-
      0.07 for Schwartz estimate) and patients older than 12 months (0.82 +/- 0.09 for
      cystatin C, 0.65 +/- 0.11 for Schwartz estimate). CONCLUSIONS: Cystatin C proved
      to be a superior marker rate over serum creatinine in estimating glomerular
      filtration in children younger than 3 years with UTMs and mild renal impairment,
      thus, offering a more specific and practical measure for monitoring GFR.

PMID- 16406934
TI  - Paraganglioma of the prostate.

PMID- 16406935
TI  - Recurrent renal cell carcinoma after laparoscopic resection.

PMID- 16406936
TI  - Magnetic resonance imaging findings and histopathological observations after
      percutaneous renal cryoablation in the rabbit model.
AB  - PURPOSE: We investigated sequential changes in MRI and relevant histopathological
      findings after PRC. MATERIALS AND METHODS: A total of 15 rabbits were examined
      with MRI and sacrificed immediately (3), and 7 (4), 45 (4) and 90 (4) days after
      PRC. MRI studies were reviewed for the signal intensity of cryolesions and
      correlated with pathological findings. MRI and pathological measurements of
      cryolesion sizes were compared using the paired t test. RESULTS: CCN was produced
      in central areas of cryolesions and associated with hemorrhage, hemolysis,
      fibrous granulation and fibrosis that was orderly through days 1 to 90. Signal
      intensity was slightly hyperintense on T1-weighted spin-echo images immediately
      after PRC, and hyperintense on T1 and T2-weighted fast spin-echo images at 7
      days. On T2-weighted fast spin-echo images there was a hypointense zone in
      peripheral areas between the central area and renal parenchyma at the prior 2
      stages, which was consistent with PCN histologically. It was enhanced at 7 days.
      At 45 and 90 days the signal intensity of cryolesions was isointense or
      hypointense on the 2 sequences. Parenchymal injury adjacent to cryolesions was
      histologically recognized and visible as a hyperintense zone in 2 lesions at 45
      days. This zone was enhanced in 2 lesions at 45 and 90 days. No statistical
      significance was apparent between the 2 measurements of cryolesions and CCN sizes
      (p <0.05). CONCLUSIONS: The MRI appearance of cryolesions reflects orderly
      histopathological findings. MRI distinguishes CCN from PCN, reveals injury to the
      renal parenchyma outside of cryolesions and accurately estimates the size of
      cryolesions and CCN.

PMID- 16406937
TI  - Novel virtual biopsy of the kidney with near infrared, reflectance confocal
      microscopy: a pilot study in vivo and ex vivo.
AB  - PURPOSE: Current diagnostic strategies for the kidney combine noninvasive imaging
      techniques with invasive procedures such as needle biopsy. However, renal needle
      biopsy is not devoid of risks, such as bleeding or infection. Additionally,
      histology studies are limited to ex vivo morphology and processing induces tissue
      artifacts, is time-consuming and limits the performance of further studies. Near
      infrared, reflectance CM is a novel technique that allows high resolution optical
      sectioning through intact tissues without using any exogenous fluorescent stains.
      Contrast between structures is based on the natural differences in refractivity.
      In this pilot study we assessed the usefulness of CM in the study of the kidney
      in vivo and ex vivo. MATERIALS AND METHODS: Kidneys of live rats were imaged with
      CM. Contrast in images is based on native properties of the tissue upon being
      shone with a near infrared laser. By convention hyperrefractile structures are
      seen as white and hyporefractile structures are seen as black. CM imaging planes
      varied along the x, y and z axes of space. Images of live kidney were compared
      with those from ex vivo CM imaging and standard histology procedures. RESULTS:
      The tubules, glomeruli, vessels and interstitium were readily identified,
      revealing intracellular detail. Differences between the kidney in vivo and ex
      vivo were also observed. Experimental contrast agents further highlighted the
      nuclei. CONCLUSIONS: CM is a useful noninvasive imaging technique that is an
      adjunct to current techniques for 3-dimensional study of the kidney in vivo and
      ex vivo. Future technical developments will provide key applications during
      surgical intervention, transplantation and rapid tissue assessment.

PMID- 16406938
TI  - Novel urothelium specific gene expression identified by differential display
      reverse transcriptase-polymerase chain reaction.
AB  - PURPOSE: Understanding the molecular basis of differential gene expression among
      different tissues at various developmental stages and in neoplastic
      transformation is an important biological goal. The potential clinical
      applications of this improved understanding are more precise diagnosis of
      disease, prediction of prognosis, novel targeted therapies and prediction of
      response to therapy. MATERIALS AND METHODS: Differential display reverse
      transcriptase-polymerase chain reaction was used to compare gene expression in
      bovine urothelium to that in autologous lung, esophagus, liver and spleen.
      Products that appeared to have urothelial specific expression were sequenced and
      assessed for homology with known sequences. Ribonuclease protection assays were
      used to further confirm the expression pattern. RESULTS: A total of 32 discrete
      cDNAs were identified, including 3 products from genes known to be urothelium
      specific in their expression, 16 with significant homology to bovine, human or
      mouse expressed sequence tags and 5 with no sequence homology to any currently
      available sequence. Urothelium specific mRNA expression was confirmed for 3 genes
      by ribonuclease protection assays and one (Udd06) was further characterized as a
      urea transporter. CONCLUSIONS: The use of differential display reverse
      transcriptase-polymerase chain reaction and other complementary techniques for
      parallel gene expression analysis will permit the complete characterization of
      the urothelial transcriptome and help identify potential molecular targets for
      rationally targeted therapy.

PMID- 16406939
TI  - Aloe-emodin induces apoptosis in T24 human bladder cancer cells through the p53
      dependent apoptotic pathway.
AB  - PURPOSE: We investigated the anticancer effect of AE (1,8-dihydroy-3
      [hydroxymethyl]-anthraquione) in the T24 human bladder cancer cell line (Food
      Industry Research and Development Institute, Hsinchu, Taiwan) by studying
      apoptosis regulation. MATERIALS AND METHODS: AE, which is purified from aloe vera
      leaves, has been reported to have antitumor activity. Cell viability, cell cycle
      and apoptosis were determined by flow cytometric methods. Levels of cyclins,
      cyclin-dependent kinase 1 and other enzyme were examined by Western blotting
      methods. RESULTS: AE inhibited cell viability, and induced G2/M arrest and
      apoptosis in T24 cells. AE increased the levels of Wee1 and cdc25c, and may have
      led to inhibition of the levels of cyclin-dependent kinase 1 and cyclin B1, which
      cause G2/M arrest. AE induced p53 expression and was accompanied by the induction
      of p21 and caspase-3 activation, which was associated with apoptosis. In
      addition, AE was associated with a marked increase in Fas/APO1 receptor and Bax
      expression but it inhibited Bcl-2 expression. CONCLUSIONS: AE induced apoptosis
      in T24 cells is mediated through the activation of p53, p21, Fas/APO-1, Bax and
      caspase-3.

PMID- 16406940
TI  - Persistence of prostatic intraepithelial neoplasia after effective
      chemoprevention of microscopic prostate cancer with antiandrogen in a rat model.
AB  - PURPOSE: We determined the chemopreventive effect of the antiandrogen
      bicalutamide (Zeneca Co., Ltd., Osaka, Japan) on Fisher 344 rat prostate
      carcinogenesis induced by DMAB (3,2'-dimethyl-4-aminobiphenyl) (Nard Co., Ltd.,
      Osaka, Japan). We have previously reported that rat prostate microscopic
      carcinogenesis in this model was paradoxically enhanced when continuous treatment
      with bicalutamide was begun 20 weeks after the initiation of DMAB. In the current
      study we determined whether antiandrogen would promote or suppress the prostate
      carcinogenesis when administration was begun at a later period of carcinogenesis.
      MATERIALS AND METHODS: DMAB at a dose of 50 mg/kg was injected subcutaneously
      into all animals 10 times at 2-week intervals. To clarify the target lesions of
      bicalutamide we used 2 control groups (groups 1 and 2). Animals in groups 1 and 2
      were autopsied at 60 and 74 weeks, respectively, after the initiation of DMAB.
      Treatment with bicalutamide began in the 60th week in group 3 rats and continued
      for 14 weeks. They were sacrificed in the 74th week. RESULTS: Microscopic cancer
      was revealed in 27% of group 1 rats and the incidence was increased to 42% in
      group 2 (statistically not significant). Delayed bicalutamide treatment
      significantly suppressed the cancer lesion. No cancerous lesion was detected in
      the ventral or other lobes of the prostate of the rats in group 3. In contrast,
      bicalutamide did not affect the incidence of PIN. The difference in the incidence
      of PIN in groups 2 and 3 (84% and 78%, respectively) was not significant.
      CONCLUSIONS: The current investigation indicates that, if bicalutamide is started
      in the later period, it can efficiently eradicate existing microscopic cancer.
      Despite this suppressive effect on microscopic cancer bicalutamide permits the
      persistence of PIN. The latter finding suggests that the sensitivity of PIN to
      antiandrogen might be more complicated than previously recognized.

PMID- 16406941
TI  - Central muscarinic receptor subtypes regulating voiding in rats.
AB  - PURPOSE: Muscarinic receptors are distributed widely in the brain. A recent study
      revealed that central muscarinic receptors are involved in voiding regulation.
      However, to our knowledge the role of each muscarinic receptor subtype has not
      been resolved. Therefore, we evaluated the effect of intracerebroventricular
      administration of selective muscarinic M1 to M4 receptor antagonists on voiding
      function in rats. MATERIALS AND METHODS: Female Sprague-Dawley rats were
      cannulated for intracerebroventricular infusion under halothane anesthesia. In
      experiment 1 cystometry was performed in conscious rats, and BC and maximal
      voiding pressure were measured. In experiment 2 a catheter was inserted via the
      bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat
      cystostomy was performed, and saline infusion and discharge saline, BC, maximal
      IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine,
      pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor
      antagonists, respectively, which were injected intracerebroventricularly.
      RESULTS: In experiment 1 pirenzepine and pFHHSiD increased BC and decreased
      maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2
      pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP.
      Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained
      unchanged. CONCLUSIONS: Intracerebroventricular administration of muscarinic M1
      and M3 receptor antagonists inhibited urination in conscious rats, while M2 and
      M4 receptor antagonists induced excitatory changes.

PMID- 16406942
TI  - Activation of alpha1D adrenergic receptors in the rat urothelium facilitates the
      micturition reflex.
AB  - PURPOSE: Previous studies have revealed that the activation of alpha(1)
      adrenergic receptors in urothelial cells releases neurotransmitters. We
      determined if alpha(1D) adrenergic receptors are expressed in the urothelium of
      the rat bladder and if inhibition of these receptors affects reflex voiding.
      MATERIALS AND METHODS: Female Wistar rats were used in the experiments. Receptor
      expression was evaluated by Western blot. The effects of receptor activation were
      studied using cystometrograms, measurement of adenosine triphosphate
      concentrations in the bladder lumen and afferent nerve recording. The alpha(1D)
      antagonist naftopidil (0.75 to 1.66 mg/kg) was administered intravenously into
      the external jugular vein. RESULTS: The expression of alpha(1D) adrenergic
      receptors was detected in urothelial tissue with Western blot and
      immunohistochemistry. The alpha(1D) receptor antagonist naftopidil prolonged the
      intercontraction interval during continuous infusion cystometrograms in conscious
      rats (143% of the control value) and suppressed the excitatory effect of
      intravesical infusion of acetic acid (0.1%) on the intercontraction interval
      (220%). Naftopidil inhibited the bladder afferent nerve activity induced by
      bladder distention (32.0%) and acetic acid infusion (30.4%), and decreased
      adenosine triphosphate levels in the bladder perfusate during bladder distention
      (36.6%). CONCLUSIONS: Endogenous catecholamines appear to act on alpha(1D)
      receptors in the urothelium to facilitate mechanosensitive bladder afferent nerve
      activity and reflex voiding.

PMID- 16406943
TI  - Human muscarinic receptor binding characteristics of antimuscarinic agents to
      treat overactive bladder.
AB  - PURPOSE: We characterized the binding affinities of several antimuscarinic agents
      in human muscarinic receptors. MATERIALS AND METHODS: Competitive inhibitory
      effects of antimuscarinic agents on specific NMS [H] (PerkinElmer Life Sciences,
      Boston, Massachusetts) binding were examined in human tissue homogenates and in
      CHO-K1 cell membranes expressing human muscarinic receptor subtypes. RESULTS:
      Oxybutynin, propiverine, tolterodine, the respective metabolites DEOB, DPr-P-4(N-
      >O) and 5-HM, and darifenacin inhibited in concentration dependent fashion
      specific [(3)H]NMS binding in homogenates of the human bladder and parotid gland
      as well as in membranes of CHO-K1 cell lines expressing human muscarinic M(1) to
      M(5) receptor subtypes. Based on inhibition constant values the inhibitory
      effects of tolterodine, 5-HM and DPr-P-4(N-->O) were 1.4 to 1.7 times greater in
      the bladder than in the parotid gland, whereas the inhibitory effects of
      oxybutynin, DEOB, propiverine and darifenacin were 2 to 10 times greater in the
      parotid gland. Consequently tolterodine, 5-HM and DPr-P-4(N-->O) compared with
      oxybutynin, DEOB, propiverine and darifenacin were found to show 3 to 4 times
      greater affinity to muscarinic receptors in the human bladder than in the parotid
      gland. Tolterodine and 5-HM were 2-fold more potent for inhibiting specific
      [(3)H]NMS binding at cell membranes expressing the M(2) vs the M(3) subtype.
      Conversely oxybutynin, DEOB, propiverine, DPr-P-4(N-->O) and darifenacin showed 2
      to 22 times higher affinity to the M(3) than to the M(2) subtype. CONCLUSIONS:
      Compared with oxybutynin, tolterodine, 5-HM and DPr-P-4(N-->O) may bind more
      selectively to muscarinic receptors in the human bladder than in the parotid
      gland.

PMID- 16406944
TI  - Characterization of spontaneous depolarizations in smooth muscle cells of the
      Guinea pig prostate.
AB  - PURPOSE: We characterized the electrical events recorded in small segments of the
      dorsal lobe of the prostate of immature male guinea pigs and examined some
      mechanisms underlying their generation. MATERIAL AND METHODS: Membrane potential
      recordings were made in the stroma of the guinea pig prostate using conventional
      single microelectrode techniques. RESULTS: Three distinct, spontaneously
      occurring electrical events were recorded in guinea pig prostate, namely slow
      waves, consisting of a depolarizing transient 14 mV in amplitude with 1 to 6
      nifedipine sensitive spikes superimposed, pacemaker potentials, consisting of a
      larger depolarization 40 mV in amplitude, and STDs 1 to 10 mV in amplitude. Only
      spikes on slow waves were inhibited by nifedipine. The depolarizing transient of
      slow waves, pacemaker potentials and STDs were abolished by cyclopiazonic acid, a
      blocker of the SERCA pump, and the mitochondrial uncoupler cyanide m-chlorophenyl
      hydrazone as well as upon exposure to Ca(2+)-free saline or the Cl(-) channel
      blockers niflumic acid and anthracene-9-carboxylic acid (Sigma Chemical Co., St.
      Louis, Missouri). Examination of the stochastic properties of STDs revealed that
      they were not well modeled by Poisson statistics, but rather they occurred in a
      clustered manner, such they may well underlie pacemaker potential generation.
      CONCLUSIONS: Guinea pig prostate shows STD and pacemaker potentials that arise
      from the release of Ca(2+) from intracellular stores and the activation of Ca(2+)
      activated Cl(-) channels. We speculate that the depolarizing transient of
      prostatic slow waves is the propagated response of pacemaker potentials evoked at
      sites electrically distant from the recording electrode.

PMID- 16406945
TI  - Experimental diabetes alters connexin43 derived gap junction permeability in
      short-term cultures of rat corporeal vascular smooth muscle cells.
AB  - PURPOSE: Intercellular communication through gap junctions was assessed in 8 to
      10-week STZ diabetic rats to evaluate diabetes related effects on gap junctional
      conductance and permeability in short-term cultures of corporeal myocytes.
      MATERIALS AND METHODS: Rats were made diabetic by a single intraperitoneal
      injection of STZ. Eight to 10 weeks later erectile function was evaluated in vivo
      and corporeal tissue was harvested to isolate corporeal myocytes. Dual whole cell
      patch clamp studies of intercellular communication through connexin43 (Cx43)
      derived gap junction channels were done in short-term, ie passages 0 to 2,
      cultured corporeal myocytes excised from STZ diabetic rats with documented
      erectile impairment as well as in myocytes from age matched control rats.
      RESULTS: No differences in macroscopic junctional conductance, single channel
      conductance or open probability were detected between myocytes from age matched
      control and STZ diabetic rats, confirming the lack of diabetes related
      alterations in Cx43 gating or conductance. However, fluorescence dye transfer
      experiments revealed a marked 3-fold increase in Cx43 mediated junctional
      permeability in the absence of any detectable change in Cx43 protein expression.
      CONCLUSIONS: These data suggest that an alteration in the selectivity filter of
      Cx43 in diabetic animals affects the permeability of specifically sized and
      charged solutes. To our knowledge these studies provide the first evidence of a
      diabetes related increase in intercellular permselectivity in corporeal myocytes
      and, thus, they may have important implications for diabetes related erectile
      dysfunction.

PMID- 16406946
TI  - Re: A clinical pathway for laparoscopic pyeloplasty decreases length of stay.

PMID- 16406947
TI  - Re: Urinary fistulas following external radiation or permanent brachytherapy for
      the treatment of prostate cancer.

PMID- 16406949
TI  - Re: Recurrence and survival following laparoscopic radical nephroureterectomy
      with various forms of bladder cuff control.

PMID- 16406951
TI  - Re: Impact of malpractice caps on use and outcomes of radical cystectomy for
      bladder cancer: data from the surveillance, epidemiology, and end results
      program.

PMID- 16406952
TI  - Re: Sexual function in women with pelvic organ prolapse compared to women without
      pelvic organ prolapse.

PMID- 16406953
TI  - Re: The increasing incidence of newborn circumcision: data from the nationwide
      inpatient sample.

PMID- 16406955
TI  - Re: Urogenital surgery of the 15th century in Anatolia.

PMID- 16406960
TI  - A "tipping point" in surgical education: simulation at the gates.

PMID- 16406961
TI  - Eliminate the term "superficial" bladder cancer.

PMID- 16406962
TI  - Refining prostate biopsy strategies.

PMID- 16406963
TI  - Sentinel lymph node mapping in prostate cancer: opportunities remain to identify
      truly positive nodes.

PMID- 16406964
TI  - Urinary incontinence--who should we trust and what should be asked?

PMID- 16406965
TI  - The natural history of observed enhancing renal masses: meta-analysis and review
      of the world literature.
AB  - PURPOSE: Standard therapy for an enhancing renal mass is surgical. However,
      operative treatment may not be plausible in all clinical circumstances. Data on
      the natural history of untreated enhancing renal lesions is limited but could
      serve as a decision making resource for patients and physicians. We examined
      available data on the natural history of observed solid renal masses. MATERIALS
      AND METHODS: A Medline review of the literature was performed from 1966 to the
      present regarding untreated, observed, localized solid renal masses. To these
      data we added our institutional experience with a total of 61 lesions observed in
      49 patients for a minimum of 1 year. Variables examined were initial lesion size
      at presentation, growth rate, duration of followup, pathological findings and
      progression to metastatic disease. Overall weighted mean estimates were
      calculated for lesion size at presentation, growth rate and followup based upon
      combining single institutional series with complete information. RESULTS: We
      identified 10 reports from 9 single institutional series in the world literature
      regarding the natural history of untreated solid localized renal lesions. The
      series included 6 to 40 patients (mean 25) with a mean followup of 30 months
      (range 25 to 39). When combined with our institutional data, a total of 286
      lesions were analyzed, of which 234 could be included in the meta-analysis. Mean
      lesion size at presentation was 2.60 cm (median 2.48, range 1.73 to 4.08). Meta
      analysis revealed a mean growth rate of 0.28 cm yearly (median 0.28, range 0.09
      to 0.86) at a mean followup of 34 months (median 32, range 26 to 39) in all
      series combined. Pathological confirmation was available in 46% of the cases (131
      of 286) and it confirmed 92% (120 of 131) as RCC variants. Evaluable data in this
      subset of confirmed RCC demonstrated a mean growth rate of 0.40 cm yearly (median
      0.35, range 0.42 to 1.6). Lesion size at presentation did not predict the overall
      growth rate (p = 0.46). Progression to metastatic disease was identified in only
      1% of lesions (3 of 286) during followup. CONCLUSIONS: The majority of small
      enhancing renal masses grow at a slow rate when observed. Although metastatic and
      cancer specific death are low, serial radiographic data alone are insufficient to
      predict the true natural history of these lesions. Therefore, physicians and
      patients assume a calculated risk when following these tumors. Basic biological
      data are needed to assess the natural history of untreated renal masses.

PMID- 16406966
TI  - Targeting death receptors in bladder, prostate and renal cancer.
AB  - PURPOSE: We describe key components of normal and aberrant death receptor
      pathways, the association of these abnormalities with tumorigenesis in bladder,
      prostate and renal cancer, and their potential application in novel therapeutic
      strategies targeted toward patients with cancer. MATERIALS AND METHODS: A MEDLINE
      literature search of the key words death receptors, TRAIL (tumor necrosis factor
      related apoptosis inducing ligand), FAS, bladder, prostate, renal and cancer was
      done to obtain information for review. A brief overview of the TRAIL and FAS
      death receptor pathways, and their relationship to apoptosis is described.
      Mechanisms that lead to nonfunction of these pathways and how they may contribute
      to tumorigenesis are linked. Current efforts to target death receptor pathways as
      a therapeutic strategy are highlighted. RESULTS: Activation of tumor cell
      expressing death receptors by cytotoxic immune cells is the main mechanism by
      which the immune system eliminates malignant cells. Death receptor triggering
      induces a caspase cascade, leading to tumor cell apoptosis. Receptor gene
      mutation or hypermethylation, decoy receptor or splice variant over expression,
      and downstream inhibitor interference are examples of the ways that normal
      pathway functioning is lost in cancers of the bladder and prostate. Targeting
      death receptors directly through synthetic ligand administration and blocking
      downstream inhibitor molecules with siRNA or antisense oligonucleotides represent
      novel therapeutic strategies under development. CONCLUSIONS: Research into the
      death receptor pathways has demonstrated the key role that pathway aberrations
      have in the initiation and progression of malignancies of the bladder, prostate
      and kidney. This new understanding has resulted in exciting approaches to restore
      the functionality of these pathways as a novel therapeutic strategy.

PMID- 16406967
TI  - Female sexual dysfunction following vaginal surgery: a review.
AB  - PURPOSE: Depending on age it has been estimated that up to 40% of women have
      complaints of sexual problems, including decreased libido, vaginal dryness, pain
      with intercourse, decreased genital sensation and difficulty or inability to
      achieve orgasm. In this review we address the etiologies and incidence,
      evaluation and treatment of female sexual dysfunction following vaginal surgery
      for indications such as stress urinary incontinence and pelvic organ prolapse;
      anterior/posterior colporrhaphy, perineoplasty and vaginal vault prolapse.
      MATERIALS AND METHODS: Literature on the mechanisms by which vaginal surgery
      affects female sexual function are discussed along with related pathophysiology
      to potential causes. The anatomy, neurovascular supply of the clitoris and
      introitus, and intrapelvic nerve supply are discussed as related to vaginal
      surgery. Techniques to avoid neurovascular damage during pelvic floor surgery
      were corroborated by supporting literature. Literature regarding female sexual
      dysfunction following other procedures, such as vaginal hysterectomy, Martius
      flap interposition, and vesicovaginal and rectovaginal fistula repair were also
      discussed. RESULTS: Current literature does not support an association between
      vaginal length following vaginal surgery and sexual function. The proportion of
      women who are sexually active does not appear to be affected by vaginal surgery.
      Sling surgery for urinary incontinence does not appear to adversely affect
      overall sexual function, although individual parameters of sexual function scores
      may vary, eg a significant percent of women report pain during intercourse. Some
      patients experience improved overall sexual function due to complete relief from
      coital incontinence CONCLUSIONS: Symptomatic vaginal narrowing is rare even in
      women undergoing simultaneous posterior repair. Overall sexual satisfaction
      appears to be independent of therapy for urinary incontinence or prolapse. Data
      indicate that defect specific posterior colporrhaphy with the avoidance of
      levator ani plication may improve sexual function. The possible etiological
      factors for sexual dysfunction following vaginal surgery deserve further
      investigations.

PMID- 16406968
TI  - Computerized tomography guided percutaneous renal cryoablation with the patient
      under conscious sedation: initial clinical experience.
AB  - PURPOSE: We report on our initial clinical experience with CT guided percutaneous
      renal cryoablation. MATERIALS AND METHODS: CT guided percutaneous renal
      cryoablation was performed on 27 tumors using conscious sedation in 20 patients.
      Eligible patients had tumors of 5 cm or less and were poor surgical candidates or
      otherwise warranted nephron sparing treatment. Tumors were classified as central
      or noncentral depending on their relationship to the renal sinus fat. During
      cryoablation intraoperative active ice ball formation was monitored with real
      time CT imaging to ensure adequate tumor coverage. Postoperative followup imaging
      was obtained at regular intervals. RESULTS: Our method appears technically
      feasible as of the 27 cryoablations performed, only 1 complication occurred
      requiring blood transfusion in a patient with a large, centrally located tumor.
      To date we have 16 tumors in 12 patients with imaging followup of 1 month or more
      (mean followup 5.9 months). Mean baseline tumor size in this group was 2.5 cm
      with 11 small (3 cm or less) and 5 large (more than 3 cm) tumors. Of the tumors 5
      were centrally located and 11 were noncentrally located. Preliminary data suggest
      that of the 16 cryoablated tumors 15 showed no signs of enhancement on followup.
      CONCLUSIONS: CT guided percutaneous renal cryoablation appears to be a feasible
      treatment option for small, noncentrally located renal tumors. While early
      results appear promising, longer followup is needed to more clearly define the
      role of this treatment method.

PMID- 16406970
TI  - Laparoscopic partial nephrectomy in solitary kidney.
AB  - PURPOSE: We report our experience with LPN for tumor in a solitary kidney.
      MATERIALS AND METHODS: Of 430 patients undergoing LPN since February 1999 at our
      institution 22 (5%) underwent LPN for tumor in a solitary kidney, as performed by
      a single surgeon. The laparoscopic technique that we used duplicated open
      principles, including hilar clamping, cold cut tumor excision and sutured renal
      reconstruction. RESULTS: Mean tumor size was 3.6 cm (range 1.4 to 8.3, median 3
      cm), median blood loss was 200 cc (range 50 to 500), warm ischemia time was 29
      minutes (range 14 to 55), total operative time was 3.3 hours (range 2.2 to 4.5)
      and hospital stay was 2.8 days (range 1.3 to 12). Two cases (9%) were electively
      converted to open surgery. Pathological findings confirmed renal cell carcinoma
      in 16 patients (73%) with negative surgical margins in all those with LPN. Major
      complications occurred in 3 patients (15%) and minor complications developed in 7
      (32%). Median preoperative and postoperative serum creatinine (1.2 and 1.5 mg/dl)
      and estimated glomerular filtration rate (67.5 and 50 ml per minute per 1.73 m2)
      reflected a change of 33% and 27%, respectively, which appeared proportionate to
      the median amount of kidney parenchyma excised (23%). One patient (4.5%) required
      temporary hemodialysis. At a median followup of 2.5 years (range 0.5 to 4.5)
      cancer specific and overall survival was 100% and 91%, respectively. No patient
      with LPN had local or port site recurrence, or metastatic disease. CONCLUSIONS:
      LPN can be performed efficaciously and safely in select patients with tumor in a
      solitary kidney. To our knowledge we present the largest series in the
      literature. Advanced laparoscopic experience and expertise are necessary in this
      high risk population.

PMID- 16406971
TI  - Laparoscopic partial nephrectomy: 3-year followup.
AB  - PURPOSE: LPN is a viable alternative to open partial nephrectomy for select small
      renal tumors. However, published intermediate term oncological data are sparse.
      We present our experience with LPN for tumor in 100 patients with a minimum
      followup of 3 years. MATERIALS AND METHODS: Of the 480 LPNs performed at our
      institution a minimum followup of 3 years is available in 100 patients since
      1999. Overall and cancer specific survival data were obtained from patient
      charts, radiographic reports and direct telephone calls to patient families.
      RESULTS: All 100 cases were completed laparoscopically without open conversion.
      Mean tumor size was 3.1 cm and mean warm ischemia was 27 minutes. Final
      histopathology revealed renal cell carcinoma in 68 patients, including 1 with
      positive surgical margins. A second patient with oncocytoma had a positive
      surgical margin. At a median followup of 42 months (mean 42.6, range 24.3 to
      62.5) no patient had evidence of local or port site recurrence. Two patients with
      renal cell carcinoma had a contralateral renal mass. Overall survival was 86% and
      cancer specific survival was 100%. Mean preoperative and postoperative serum
      creatinine was 1.1 and 1.3 mg/dl, respectively. Two patients with preoperative
      chronic renal insufficiency were undergoing hemodialysis. CONCLUSIONS: At 3-year
      followup LPN provides oncological outcomes comparable to those in contemporary
      open partial nephrectomy series.

PMID- 16406972
TI  - Micropapillary carcinoma of the renal pelvis and ureter.
AB  - PURPOSE: MPC located in the upper urinary tract is rare with only 2 cases
      reported to date. We report clinical and histopathological data on 26 patients to
      increase the knowledge of this rare entity. MATERIALS AND METHODS: A clinical and
      histopathological review was performed in 943 patients with a neoplasm in the
      renal pelvis or ureter, diagnosed between 1971 and 1998. We identified 26
      patients with MPC. No patients were alive at the end of the study. RESULTS: Of
      the patients 11 had greater than 50% MPC and 15 had focal MPC (at least 10%). The
      incidence was 2.8%. Median patient age at diagnosis was 69 years (range 54 to 88)
      and the male-to-female ratio was 17:9. All except 4 patients had stage T3 disease
      or higher. Carcinoma in situ was identified in 64% of cases and vascular invasion
      was present in 81%. A total of 20 patients (77%) died of disease and only 7
      survived longer than 5 years. CONCLUSIONS: The prognosis is poor since most
      patients with MPC of the renal pelvis and ureter initially present with advanced
      disease. Stage for stage the prognosis is not different from that in nonMPC
      urothelial cell carcinoma. Surgery is curative in less advanced cases. However,
      radiotherapy and systemic chemotherapy appear to be ineffective.

PMID- 16406974
TI  - North American white mitochondrial haplogroups in prostate and renal cancer.
AB  - PURPOSE: While the mitochondrion is known to be a key mediator of apoptosis,
      there has been little inquiry into the inheritance pattern of mitochondria in
      patients with cancer. We compared the mtDNA haplotype in patients with prostate
      and renal cancer to that in controls to determine if there is an association
      between mitochondrial genotype and cancer. MATERIALS AND METHODS: Haplotyping was
      performed using polymerase chain reaction/digest identification of key
      polymorphic sites in the mitochondrial genome. A total of 121 and 221 white men
      with renal and prostate cancer, respectively, were identified following
      pathological confirmation of cancer, while 246 white controls were selected
      randomly from a bank of cadaveric organ donor DNA. Statistical analysis was
      performed and ORs were calculated. RESULTS: Mitochondrial haplogroup U was a
      highly significant risk factor for prostate and renal cancer vs controls (16.74%
      and 20.66% vs 9.35%, Fisher's exact test p = 0.019 and 0.005, respectively). The
      association remained statistically significant in renal cancer even after
      Bonferroni adjustment for multiple comparisons. Haplogroup U carried an OR of
      1.95 for prostate cancer and an OR of 2.52 for renal cancer. CONCLUSIONS: The
      inheritance of mitochondrial haplogroup U is associated with an approximately 2
      fold increased risk of prostate cancer and 2.5-fold increased risk of renal
      cancer in white North American individuals. Therefore, individuals with this
      mitochondrial haplotype are in a high risk group. Because mitochondrial
      haplogroup U is found in 9.35% of the white United States population, there are
      more than 20 million individuals in this high risk group.

PMID- 16406976
TI  - Neuro-fuzzy modeling: an accurate and interpretable method for predicting bladder
      cancer progression.
AB  - PURPOSE: New methods are required to improve the prediction of cancer progression
      as traditional statistical tests have limited accuracy. Accurate predictions
      would allow physicians to offer specific treatment according to individual
      patient risk. While predictive improvements are obtained using ANN, the hidden
      nature of these networks prevents insight and has hindered their widespread
      implementation. NFM is an alternate form of artificial intelligence using fuzzy
      logic (which is a multivalued logic which provides reasoning under uncertainty).
      By defuzzification the NFM rule base becomes transparent to overcome the black
      box nature of ANN. MATERIALS AND METHODS: Combinations of clinicopathological
      (tumor stage and grade, patient age, gender, and smoking status) and molecular
      (immunohistochemical expression of p53 and methylation status of 11 loci) data
      from 117 patients were used to develop and compare predictive models of tumor
      progression using NFM, ANN and LR. RESULTS: NFM (88% to 100% sensitivity, 97% to
      100% specificity and 94% to 100% accuracy) predicted the presence and timing of
      cancer progression more accurately than ANN (81% to 87%, 95% to 100% and 89% to
      90%, p = 0.002) and LR 3%, 61% to 72% and 47% to 53%, p = 0.00005). NFM was able
      to interrogate the clinicopathological and molecular data, and select the most
      important parameters (age, grade, stage, smoking, methylation) for progression
      prediction. CONCLUSIONS: Intelligent systems and molecular biomarkers improved
      the accuracy of cancer progression predictions. NFM appeared superior to ANN in
      terms of accuracy, sensitivity, specificity and transparency. The use of NFM in
      routine clinical practice warrants further validation.

PMID- 16406977
TI  - Saturation technique does not improve cancer detection as an initial prostate
      biopsy strategy.
AB  - PURPOSE: We reported on the results of a sequential cohort study comparing office
      based saturation prostate biopsy to traditional 10-core sampling as an initial
      biopsy. MATERIALS AND METHODS: Based on improved cancer detection of office based
      saturation prostate biopsy repeat biopsy, we adopted the technique as an initial
      biopsy strategy to improve cancer detection. Two surgeons performed 24-core
      saturation prostate biopsies in 139 patients undergoing initial biopsy under
      periprostatic local anesthesia. Indication for biopsy was an increased PSA of 2.5
      ng/dl or greater in all patients. Results were compared to those of 87 patients
      who had previously undergone 10-core initial biopsies. RESULTS: Cancer was
      detected in 62 of 139 patients (44.6%) who underwent saturation biopsy and in 45
      of 87 patients (51.7%) who underwent 10-core biopsy (p >0.9). Breakdown by PSA
      level failed to show benefit to the saturation technique for any degree PSA
      increase. Men with PSA 2.5 to 9.9 ng/dl were found to have cancer in 53 of 122
      (43.4%) saturation biopsies and 26 of 58 (44.8%) 10-core biopsies. Complications
      included 3 cases of prostatitis in each group. Rectal bleeding was troublesome
      enough to require evaluation only in 3 men in the saturation group and 1 in the
      10-core group. CONCLUSIONS: Although saturation prostate biopsy improves cancer
      detection in men with suspicion of cancer following a negative biopsy, it does
      not appear to offer benefit as an initial biopsy technique. These findings
      suggest that further efforts at extended biopsy strategies beyond 10 to 12 cores
      are not appropriate as an initial biopsy strategy.

PMID- 16406978
TI  - Making sense of prostate specific antigen: improving its predictive value in
      patients undergoing prostate biopsy.
AB  - PURPOSE: The clinical usefulness of PSA for prostate cancer screening is unclear,
      although the test remains in common use. New methods to interpret PSA are needed.
      MATERIALS AND METHODS: We examined a cohort of 2,637 men who underwent prostate
      biopsies for abnormal DRE or PSA between 1999 and 2004. Using risk factors for
      prostate cancer, including patient age, ethnicity, family history of prostate
      cancer, previous negative biopsy, voiding symptoms and prostate volume, we
      developed risk groups for prostate cancer using recursive partitioning modeling
      independent of PSA or DRE. We then compared prostate cancer probabilities by PSA
      ranges by risk group. RESULTS: Of the 2,637 men 1,282 (48.6%) had prostate
      cancer. Age, ethnicity, family history, previous negative biopsy and prostate
      volume were predictive for cancer. We constructed 6 risk groups by combining
      these factors and created tables to assign patients to these groups. Independent
      of PSA and DRE the probability of cancer ranged from 15% in patients in group 1
      to 78% in patients in group 6 (p <0.0001). By adding PSA and DRE to each risk
      group prostate cancer probabilities were refined from 0% to 100%. Patients in the
      higher risk groups also had higher grade cancer (p <0.0001). CONCLUSIONS: We
      generated 6 risk groups based on simple risk factors for prostate cancer. When
      used in the right context and patient, PSA is highly accurate for predicting
      prostate cancer and permitting rational decision making in patients with abnormal
      PSA.

PMID- 16406979
TI  - Virtual microscopy in prostate histopathology: simultaneous viewing of biopsies
      stained sequentially with hematoxylin and eosin, and alpha-methylacyl-coenzyme A
      racemase/p63 immunohistochemistry.
AB  - PURPOSE: Histopathological diagnosis of small focus carcinomas in prostatic
      needle biopsies is often assisted by IHC. To make a definitive diagnosis the
      pathologist must compare IHC findings with hematoxylin and eosin stained tissue
      morphology. We introduce what is to our knowledge a new application of virtual
      microscopy, in which hematoxylin and eosin, and IHC stains done sequentially on
      the same microscope slide can be simultaneously displayed and compared on a
      computer screen. MATERIALS AND METHODS: A total of 30 hematoxylin and eosin
      stained prostatic needle biopsies were scanned with a computer controlled
      microscope. The slides were destained and then immunostained with a cocktail of
      AMACR and p63 antibodies, which labels the nuclei of nonmalignant basal cells
      (p63) and the cytoplasm of neoplastic glandular cells suspicious for malignancy
      (AMACR). The slides were then scanned again and the pairs of virtual slides were
      aligned for synchronized viewing. RESULTS: The presented technique was found
      helpful when suspicious lesions were small and when examining the immunoprofile
      of specimens was warranted, in addition to examining hematoxylin and eosin
      stained tissue morphology. The usefulness of our approach based on virtual
      microscopy can be evaluated on the website , which also serves as an educational
      tool for self-learning the correlation between hematoxylin and eosin stained
      tissue morphology, and AMACR/p63 IHC in prostate biopsies. CONCLUSIONS: The
      technology for simultaneously viewing sequentially hematoxylin and eosin and IHC
      stained prostate biopsies can be readily used for educational purposes, as
      exemplified by our website, and along with the availability of rapid virtual
      slide scanners it can also be used for clinical diagnostics.

PMID- 16406980
TI  - Obesity, serum prostate specific antigen and prostate size: implications for
      prostate cancer detection.
AB  - PURPOSE: Obesity has been associated with lower serum testosterone, theoretically
      resulting in decreased PSA production. Obesity has also been associated with
      prostatic enlargement, making the detection of existent cancer more difficult.
      Together these findings would result in an apparent protective effect of obesity
      on prostate cancer risk due to technical detection issues unrelated to cancer
      biology. We examined the association between BMI, and PSA and prostate weight in
      a cohort of men undergoing RP. MATERIALS AND METHODS: We evaluated the
      association of BMI with prostate weight and PSA using linear regression,
      adjusting for patient age at RP, year of RP, race, and pathological stage and
      grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access
      medical centers that comprise the Shared Equal Access Regional Cancer Hospital
      Database. RESULTS: On multivariate analysis increasing BMI was associated with
      increasing prostate weight but only in men younger than 63 years and not in men
      63 years or older (p-trend <0.001 and 0.44, respectively). In men younger than 63
      years mean multivariate adjusted prostate weight +/- SE in those with a BMI of
      less than 25 vs 30 to 34.9 kg/m was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no
      significant association between BMI and preoperative PSA (p-trend = 0.70).
      CONCLUSIONS: In a cohort of men undergoing RP obesity was associated with larger
      prostate size but only in younger men. There was no association between BMI and
      PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger
      obese men in this study would be expected to result in a modest decrease in the
      odds of detecting prostate cancer in a contemporary series of PSA screened men
      due to the decreased sensitivity of cancer detection related to larger prostate
      size. Obesity may appear protective for prostate cancer in younger men due to
      technical issues unrelated to cancer biology.

PMID- 16406982
TI  - Evidence for a biopsy derived grade artifact among larger prostate glands.
AB  - PURPOSE: The PCPT has demonstrated a higher incidence of high grade (Gleason
      pattern 4 or greater) prostate cancers among men randomized to finasteride. One
      plausible explanation for this finding is that tumor grade as assigned by TRUS
      guided biopsy is artifactually associated with prostate volume. MATERIALS AND
      METHODS: We evaluated our institutional data set of TRUS guided biopsies in the
      last 3 years and identified 369 cases of prostate cancer that fit the criteria of
      PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified
      risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens
      from the same patients using univariate and multiple logistic regression
      analyses. Assessed covariates included patient age, PSA and TRUS volume. RESULTS:
      Risk factors for Gleason pattern 4 or greater in the biopsy specimens included
      age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p =
      0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant
      of Gleason pattern 4 or greater on multivariable analysis. Although prostate
      volume was a predictor for biopsy derived high grade disease it was not
      predictive of true histological grade. CONCLUSIONS: These data suggest that
      simply having a larger prostate results in fewer high grade cancers diagnosed at
      biopsy. Prostatectomy results in the same men suggest sampling artifact, as the
      distribution of cancer grade is not associated with prostate volume. These
      findings provide evidence that the increase in higher grade tumors among men in
      the finasteride arm of PCPT may simply result from prostate volume reduction.

PMID- 16406983
TI  - Relationship among initial serum prostate specific antigen, prostate specific
      antigen progression and prostate cancer detection at repeat screening visits.
AB  - PURPOSE: We evaluated the probability of positive serum PSA (3 ng/ml or greater)
      and CaP detection at annual followup visits in men with negative initial PSA
      (less than 3 ng/ml) to optimize the re-screening schedule. MATERIALS AND METHODS:
      Data on 5,387 men 45 to 80 years old with negative PSA and no CaP diagnosis at
      the first screening visit were obtained from the Laval University Prostate Cancer
      Screening Program database. Accelerated failure time regressions were fitted to
      time from baseline to positive PSA and to time from positive PSA to CaP
      detection. The models were combined to estimate the cumulative probability of
      positive PSA followed by CaP detection at re-screening. RESULTS: The 5-year
      cumulative probability of detecting CaP at annual visits in men with baseline PSA
      up to 1.5 ng/ml remained below 0.8%, while it was 1.3%, 4.8% and 8.3% in men with
      PSA 1.5 to less than 2, 2 to less than 2.5 and 2.5 to less than 3 ng/ml,
      respectively. Time to positive PSA significantly decreased with increasing
      baseline PSA and age, while the time between positive PSA and CaP detection
      depended only on age. Men with PSA below 1.0 ng/ml could wait for 4 to 5 years
      before being re-tested, while men with PSA between 1.0 and 1.5 ng/ml should be
      screened every second year and men with PSA 1.5 ng/ml or greater should be
      screened every year. CONCLUSIONS: The proposed retesting schedule using current
      PSA and age decreases the number of visits by 38.1%, while delaying the detection
      of only 2.4% of CaPs that would have been detected using annual PSA testing.

PMID- 16406985
TI  - Preoperative parameters, including percent positive biopsy, in predicting seminal
      vesicle involvement in patients with prostate cancer.
AB  - PURPOSE: Complete dissection of the SVs during RP can contribute to increased
      morbidity including erectile dysfunction and incontinence. Therefore we evaluated
      the clinical parameters associated with a positive SV finding on final pathology
      and identified those patients with a minimal risk of SV involvement for potential
      SV sparing surgery. MATERIALS AND METHODS: We retrospectively reviewed our RP
      database from 1991 to 1999 to evaluate the incidence and clinical correlates of
      SV invasion. Variables studied included preoperative total serum PSA, percent
      positive biopsy cores, DRE and biopsy Gleason score. Statistical analysis
      included univariate, multivariate regression analysis and ROC curves. RESULTS: Of
      our 1,056 patients 79 (7.4%) had SV involvement. Of the 356 patients with less
      than 17% positive biopsies, only 2 (0.5%) had SV involvement on final pathology.
      Preoperative PSA, biopsy Gleason score and percent positive biopsies were all
      highly predictive of SV invasion on multivariate analysis. Percent positive
      biopsy was found to be the single best predictor of seminal vesicle invasion (p
      <0.0001). CONCLUSIONS: In our series percent positive biopsy was the single best
      predictor of SV invasion at the time of RP. An analysis of preoperative
      parameters including percent positive biopsy, biopsy Gleason score and
      preoperative PSA may define a subset of patients in which prospective studies
      could be used to determine the value and safety of SV sparing surgery.

PMID- 16406987
TI  - Association between an estrogen receptor alpha gene polymorphism and the risk of
      prostate cancer in black men.
AB  - PURPOSE: Studies suggest that SNPs within ESR1 may be associated with an
      increased risk of prostate cancer. We evaluated the association of the XbaI and
      PvuII ESR1 SNPs and prostate cancer risk in 3 different racial/ethnic
      populations. MATERIALS AND METHODS: A total of 1,603 volunteers from the SABOR
      study (285 black, 876 white and 442 Hispanic men) were genotyped to assess
      allelic frequencies of the ESR1 SNPs. Case-control analysis was performed on 598
      prostate cancer cases and 1,098 controls (260 black men, 1,013 non-Hispanic white
      men and 423 Hispanic white men) to assess the association between these
      polymorphisms and prostate cancer risk. RESULTS: Allelic frequency was
      significantly different across ethnic/racial groups for both SNPs. Logistic
      regression analysis adjusted for age and stratified by race and ethnicity
      demonstrated an association between the AG genotype or presence of the G allele
      (GG or AG genotype) in the XbaI SNP and prostate cancer risk within black men (OR
      2.25, 95% CI 1.07-4.70, p = 0.031; OR 2.14, 95% CI 1.05-4.35, p = 0.035,
      respectively). No association was observed among Hispanic and non-Hispanic white
      men for this SNP. Furthermore, there was no association between the PvuII SNP and
      prostate cancer risk across all groups. CONCLUSIONS: Our study demonstrates an
      association between the AG genotype, as well as presence of the G allele within
      the XbaI ESR1 SNP and prostate cancer risk among black men.

PMID- 16406988
TI  - Biological correlates of p27 compartmental expression in prostate cancer.
AB  - PURPOSE: As one of the cyclin-dependent kinase inhibitors, p27 has been
      associated with biological behavior and disease progression in malignancies.
      MATERIALS AND METHODS: Tissue microarrays were constructed using 640 radical
      prostatectomy specimens. Normal prostate tissue, benign prostatic hyperplasia and
      index tumor were cored in triplicate at 0.6 mm. Slides were stained with an
      antibody to p27 and digitized. The expression of p27 was quantified. SPSS 11.0
      (SPSS, Chicago, Illinois) was used to perform the Spearman correlation test,
      Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: We noted
      p27 expression predominately located in the epithelial nuclei of benign and
      cancer tissues. In PCa p27 was decreased compared to that in normal tissue, while
      p27 cytoplasmic expression was increased in PCa. Moderate nuclear p27 and
      cytoplasmic displacement of p27 were associated with worse disease-free survival
      compared with high or low p27. The cytoplasmic presence of p27 was an independent
      indicator for predicting the probability of biochemical recurrence in PCa.
      CONCLUSIONS: We report that p27 expression is consistently high in the normal
      prostate. Moderate levels of nuclear p27 and/or cytoplasmic entrapment of p27 are
      associated with increased proliferation and worse biochemical recurrence-free
      survival. These findings suggest that PCa may enhance its growth and progression
      by decreasing nuclear p27 via cytoplasmic displacement and other molecular
      mechanisms.

PMID- 16406989
TI  - A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous
      delivery system for leuprolide acetate for the treatment of prostate cancer.
AB  - PURPOSE: The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month
      subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins,
      Colorado) were investigated in patients with prostate cancer. MATERIALS AND
      METHODS: In this 12-month, open label, multicenter study 111 patients with
      adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously
      once every 6 months. The primary efficacy parameter was serum testosterone 50
      ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of
      28 patients. RESULTS: Of the 111 enrolled patients 103 (93%) completed the 12
      month study. Eight patients withdrew due to nonmedical reasons in 1, disease
      progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109
      remaining patients (99%) achieved testosterone suppression, while 1 who never
      attained suppression was withdrawn at day 85. Mean time to castrate suppression
      was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were
      below medical castrate testosterone levels of 50 ng/dl (mean +/- SE 12.3 +/- 2.1
      ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone
      decreased from 6.98 +/- 0.48 mIU/ml at baseline to 0.23 +/- 0.14 mIU/ml at month
      12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific
      antigen decreased 97% from 39.8 +/- 21.5 ng/ml at baseline to 1.2 +/- 0.3 ng/ml
      at 12 months. No clinically significant flare reactions were observed. The most
      common treatment related adverse event was mild to moderate hot flashes.
      CONCLUSIONS: LA-2585 (45.0 mg depot) consistently produced and maintained safe
      and effective serum testosterone suppression with total serum testosterone well
      below the medical castrate level of less than 50 ng/dl.

PMID- 16406990
TI  - Evaluation of fluid absorption during holmium laser enucleation of prostate by
      breath ethanol technique.
AB  - PURPOSE: In a prospective manner we studied various factors affecting fluid
      absorption during HoLEP. We also simultaneously evaluated changes in serum
      electrolytes and hemoglobin decrease during HoLEP. MATERIALS AND METHODS: This
      prospective study comprised of 53 patients who underwent HoLEP at our institute.
      Irrigation fluid was normal saline tagged with ethanol (1% w/v). Intraoperatively
      a standard breath analyzer was used to monitor expired breath ethanol levels
      during the procedure at 10-minute intervals. Patients who absorbed irrigating
      fluid as indicated by positive intraoperative breath tests were considered
      absorbers. Serum electrolyte and hemoglobin estimations were done before and
      after surgery. Total irrigation time, amount of irrigation fluid used, weight of
      resected tissue and presence of capsular perforation were recorded. Statistical
      analysis was performed to observe the effects of various factors on the amount of
      intraoperative fluid absorption. RESULTS: Of 53 patients studied 14 (26.41%)
      demonstrated fluid absorption in the range of 213 to 930 ml (mean 459).
      Preoperative prostate weight, total irrigation time, amount of irrigation fluid
      used and resected tissue weight were all significantly greater in absorbers.
      Similarly, absorbers had a statistically significant decrease in hemoglobin level
      postoperatively. There was no statistically significant change in serum
      electrolytes between absorbers and nonabsorbers. CONCLUSIONS: Preoperative weight
      of prostate, total irrigation time, amount of irrigation fluid used and weight of
      resected tissue all directly influence the amount of fluid absorption during
      HoLEP. There is no significant change in serum electrolytes and no risk of the
      transurethral resection syndrome.

PMID- 16406991
TI  - Perioperative complications of laparoscopic and robotic assisted laparoscopic
      radical prostatectomy.
AB  - PURPOSE: While it remains controversial whether LRP or da Vinci RAP offers any
      advantages over radical retropubic prostatectomy, LRP and RAP are being used more
      frequently. We reviewed our experience with these minimally invasive techniques.
      MATERIALS AND METHODS: We reviewed intraoperative and early postoperative
      complications of 358 LRPs performed from October 2000 to January 2003 with those
      of 322 RAPs performed from June 2003 to June 2004. The transperitoneal approach
      with bilateral pelvic lymph node dissection was performed using each technique.
      Data acquisition was done independently of the 3 surgeons. RESULTS: The LRP and
      RAP groups had similar clinical characteristics in terms of patient race, body
      mass index, prostate specific antigen, risk group, and pathological tumor grade
      and stage. Median operative time and estimated blood loss for LRP and RAP were
      4.1 and 3.1 hours, and 200 and 250 ml, respectively. No blood transfusions were
      given intraoperatively, although 8 patients with LRP (2.2%) and 5 with RAP (1.6%)
      were transfused postoperatively. Of the LRP and RAP patients 21 (5.9%) and 3
      (0.3%), respectively, experienced intraoperative complications. Postoperatively
      48 patients with LRP (13.4%) and 24 with RAP (6.8%) experienced urine leakage,
      while 19 with LRP (5.3%) and 9 with RAP (2.8%) had ileus. There were no deaths,
      myocardial infarctions, pulmonary emboli or cerebrovascular accidents.
      CONCLUSIONS: In our series surgeon experience derived from LRP may contribute to
      the lower complication rate and operative time of RAP. Dissemination of surgical
      technique and management of complications may lead to improved perioperative LRP
      and RAP morbidity. However, the morbidity of these 2 approaches compares
      favorably with that of radical retropubic prostatectomy.

PMID- 16406993
TI  - Long-term prognostic significance of primary Gleason pattern in patients with
      Gleason score 7 prostate cancer: impact on prostate cancer specific survival.
AB  - PURPOSE: We determined the long-term clinical significance of primary Gleason
      pattern in patients with Gleason score 7 prostate cancer. MATERIALS AND METHODS:
      We reviewed the records of all patients who underwent bilateral pelvic lymph node
      dissection and radical retropubic prostatectomy for Gleason score 7 prostate
      cancer at our institution. All patients who underwent adjuvant hormonal or
      radiation therapy were excluded from analysis. Patients were monitored for
      biochemical failure, that is PSA progression, systemic recurrence and cancer
      specific survival. RESULTS: We identified 1,688 patients who met admission
      criteria, of whom 1,256 (74.4%) had primary Gleason pattern 3 and 432 (25.6%) had
      primary Gleason pattern 4. Median followup was 6.9 years. At 10 years primary
      Gleason pattern 3 was associated with increased biochemical recurrence-free
      survival (48% vs 38%, p <0.001), lower systemic recurrence (8% vs 15%, p <0.001)
      and higher cancer specific survival (97% vs 93%, p = 0.013) for Gleason primary
      grades 3 and 4, respectively. All of these end points remained significant on
      multivariate analysis when controlling for preoperative PSA, seminal vesicle
      involvement, margin status, DNA ploidy and TNM staging. PSA doubling time was
      shorter in patients with primary Gleason pattern 4 (1.64 vs 1.01 years). Systemic
      recurrence and cancer specific survival were associated with a PSA doubling time
      of less than 1 year. CONCLUSIONS: Gleason score 7 prostate cancer is a
      heterogeneous entity. We should continue to stratify patients according to
      primary Gleason pattern. Patients with Gleason score 4 + 3 prostate cancer have
      more aggressive disease and experience higher rates of biochemical failure,
      systemic recurrence and cancer specific death.

PMID- 16406994
TI  - Evaluation of functional outcome and local control after radiotherapy for
      metastatic spinal cord compression in patients with prostate cancer.
AB  - PURPOSE: Patients with prostate cancer with metastatic spinal cord compression
      have better survival prognosis than other patients with MSCC and may live long
      enough to develop a local recurrence of MSCC. This study investigates prognostic
      factors and radiation schedules for functional outcome and local control of MSCC
      after radiotherapy in patients with prostate cancer. MATERIALS AND METHODS: A
      total of 281 patients irradiated between January 1992 and December 2003 were
      included. Potential prognostic factors were investigated including age,
      performance status, number of involved vertebra, pretreatment ambulatory status,
      time of developing motor deficits before RT and radiation schedule--short course
      RT (1x8/5x4 Gy) vs long course RT (10x3/15x2.5/20x2 Gy). RESULTS: Overall
      response to RT was 86% (33% improvement of motor function, 53% no further
      progression). Of the nonambulatory patients 33% regained the ability to walk. On
      multivariate analysis functional outcome was significantly affected by the time
      of developing motor deficits before RT (more than 14 days better than 8 to 14
      days and 1 to 7 days, p <0.001) and number of involved vertebrae (1 to 2 better
      than 3 or more, p = 0.013), but not by the radiation schedule (p = 0.859). The 2
      year local control of MSCC was 84% depending on the radiation schedule (better
      after long course RT, p = 0.001). CONCLUSIONS: Functional outcome after RT was
      significantly influenced by the time of developing motor deficits before RT and
      number of involved vertebra. Local control was significantly better after
      application of long course RT. Patients with a poor expected survival could be
      treated with short course RT, because a short treatment time means less
      discomfort for the patient. For patients with good survival prognosis, long
      course RT should be applied to achieve better local control.

PMID- 16406995
TI  - Outcome of penile cancer in circumcised men.
AB  - PURPOSE: We previously reported on a group of patients with post-circumcision
      carcinoma of the penis. We now study the long-term outcome of these patients.
      MATERIALS AND METHODS: We retrospectively reviewed the available charts of 22
      patients presenting between October 1979 and May 2000. RESULTS: Of 22 patients 18
      underwent ritual circumcision with extensive scar development. Median age at
      diagnosis was 62.4 years. The penile lesion was dorsal and proximally located in
      15 patients. Median delay before diagnosis was 12 months. Clinically 14 patients
      had stage T1-T2 disease, with 13 having no lymph node involvement and none with
      distant metastasis, 8 patients had stage T3-T4 disease. A total of 15 patients
      were treated surgically with total penectomy (10) or conservative local excision
      (5), inguinal lymph node dissection (9) and subsequent penile reconstruction (3).
      Pathological staging in 15 patients revealed 10 patients with stage T1 and in 8
      patients with lymph node dissection none had nodal metastasis. Histopathological
      classification was 20 squamous cell carcinoma, 1 sarcoma and 1 verrucous
      carcinoma. Six patients refused surgery and 1 was referred for palliation. Median
      followup was 14.5 months and median survival was 14.5 months. The 3-year survival
      was 42% for stage T1-T2 and 13% for T3-T4 (p = 0.0052). Median survival for the
      surgical group was 34 months whereas for nonsurgical group was 3 months (p =
      0.0016). Recurrence-free survival in the surgical group was 50%. CONCLUSIONS:
      Penile carcinoma in circumcised men is a distinct disease commonly following
      nonclassic vigorous circumcision. Delayed diagnosis and deferring surgical
      treatment are associated with increased mortality.

PMID- 16406997
TI  - Interstitial cystitis versus detrusor overactivity: a comparative, randomized,
      controlled study of cystometry using saline and 0.3 M potassium chloride.
AB  - PURPOSE: We compared cystometric findings in interstitial cystitis and detrusor
      overactivity using 0.3 M KCl and 0.9% normal saline. MATERIALS AND METHODS:
      Female patients with established diagnoses of IC (7 patients according to NIDDK
      criteria) and urodynamically proven DO (10 patients) underwent consecutive
      cystometrograms using 0.9% normal saline and 0.3 M KCl, the order of which was
      randomized for each patient. Individual CMGs were performed by separate
      investigators, and patients and investigators were blinded to the order in which
      the solutions were used and to the results of the other CMG. The results were
      analyzed on a comparative basis using a 2-tailed t test for comparison of the
      means and a Kolmogorov-Smirnov z test was used for group comparison. A ROC curve
      was used to plot sensitivity to the false-positive rate. RESULTS: Irrespective of
      the diagnosis or the type of infusion used, the volume at FDV was slightly lower
      with the first CMG compared to the second (mean 76.1 vs 94.2 ml) but did not
      reach statistical significance (p = 0.20). However, Cmax was similar for first
      and second CMGs (mean 214 vs 213.2 ml, p = 0.98). Although lower with KCl, there
      was no significant difference in FDVs obtained with either solution (mean 78.2 vs
      92.2 ml for KCl and NS, respectively, p = 0.33). However, KCl produced a
      significant reduction in Cmax across the whole group (mean 244.5 vs 182.7 ml, p =
      0.008). This was most marked in the DO group in which there was a 23% reduction
      in Cmax with KCl compared to NS, while the IC group showed only a 15% reduction
      in mean Cmax. The ROC curve, comparing Cmax values for NS with KCl cutoff values
      of 15% and 30%, resulted in poor positive predictive values (51% and 66%,
      respectively) for comparative cystometry in distinguishing IC from DO.
      CONCLUSIONS: The 0.3 M KCl reduces Cmax in IC and DO, the effect being more
      pronounced in DO. Urothelial hyperpermeability is not specific to IC. Comparative
      cystometry using NS and 0.3 M KCl does not help to differentiate IC from DO.

PMID- 16406999
TI  - External validation of outcome prediction model for ureteral/renal calculi.
AB  - PURPOSE: We externally validated a previously designed neural network model to
      predict outcome and duration of passage for ureteral/renal calculi. The model was
      also evaluated using a 6 mm largest stone dimension cutoff in predicting stone
      outcome. MATERIALS AND METHODS: The model was previously designed on 301 patients
      at Albany Medical Center (free shareware from www.uroengineering.com). The model
      had a prediction accuracy of 86% for passage outcome and 87% for passage
      duration. In this study we tested the model on a separate 384 patients from 6
      different external institutions to assess the prediction accuracy. All patients
      had a single renal/ureteral calculus by evaluation in an emergency room setting
      or by primary physicians and were then referred for further treatment. Model
      accuracy was also compared to using a 6 mm largest stone dimension cutoff in
      predicting the need for intervention. RESULTS: Testing on the 384 patients from
      all 6 external institutions revealed an outcome prediction accuracy of 88%. The
      area under the ROC curve was 0.9. Using a 6 mm stone size cutoff provided 79%
      (ROC 0.8) accuracy. The model duration of passage prediction accuracy was 80%
      (133 patients passed the stone, area under ROC of 0.8). CONCLUSIONS: The model
      provided high stone outcome prediction accuracy (ROC of 0.9 and 0.8) at the 6
      external institutions, comparable to that of the design institution. The model
      provided higher accuracy than using only the largest stone dimension as a cutoff.
      Increasing experience will further assess the model's accuracy.

PMID- 16407000
TI  - Use of lower pole nephrostomy drainage following endorenal surgery through an
      upper pole access.
AB  - PURPOSE: PNL via an UP puncture is efficient for treating complex stone disease.
      Access via the UP can provide better visualization, allowing greater stone
      clearance with a rigid instrument due to its more favorable alignment with the
      axis of the intrarenal collecting system. However, the presence of a NT through
      the upper pole tract, especially with a supracostal puncture, can generate
      significant patient discomfort. We reviewed our experience with a technique using
      tubeless UP access for PNL with concomitant placement of a NT via a LP calix.
      MATERIALS AND METHODS: We performed a retrospective review of our experience
      using tubeless UP access for PNL with concomitant placement of an LP NT for
      postoperative drainage. Patient demographics, the number and location of
      accesses, stone size, stone-free rates, concurrent/additional procedures and
      complications were recorded. RESULTS: A total of 63 tubeless UP accesses were
      performed in 62 patients undergoing PNL, including unilateral access in 61 and
      bilateral access in 1. Supracostal UP punctures were used in 58 patients,
      including 40 above the 12th, 17 above the 11th and 1 above the 10th rib. Each
      patient underwent at least 2 accesses and 3 had 3 or more accesses placed. LP
      access was nondilated in 37 patients and dilated in 26. Of the patients 56.6%
      were stone-free after a single procedure, increasing to 96.2% following secondary
      procedures. Three of the 62 patients (4.8%) required transfusion, 3 (4.8%)
      required intervention for pleural morbidity and 1 (1.6%) required a stent for a
      nonsealing upper pole access. CONCLUSIONS: Tubeless UP access provides maximal
      efficiency for stone clearance during PNL, while minimizing the morbidity of an
      intercostal tube.

PMID- 16407002
TI  - The tongue as an alternative donor site for graft urethroplasty: a pilot study.
AB  - PURPOSE: Urethroplasty with a buccal mucosal graft provides excellent clinical
      results but it may also cause oral complications in some cases. The mucosa
      covering the lateral and under surface of the tongue is identical in structure
      with that lining the rest of the oral cavity. We evaluated LMGs for
      urethroplasty. MATERIALS AND METHODS: From January 2001 to September 2004, 8 men
      34 to 65 years old (mean age 46.1) with urethral strictures 1.5 to 4.5 cm long
      were selected for 1-stage dorsal onlay urethroplasty. The site of the harvest
      graft was the lateral mucosal lining of the tongue. Postoperatively all patients
      were followed with urethrography, uroflowmetry, cystourethrography and flexible
      urethroscopy after 3 and 12 months. Successful reconstruction criteria were peak
      flow rate greater than 15 ml per second and no need for postoperative urethral
      dilation. RESULTS: Median followup was 18 months (mean 22.1, range 3 to 47).
      Seven cases were successful. One patient had a partial urethral stricture. In
      successful cases cystourethrography revealed no significant graft contractures or
      sacculations and at flexible urethroscopy LMG was almost indistinguishable from
      native urethra. There were no pain, esthetic or functional complications at the
      donor site. CONCLUSIONS: Harvesting the LMG is feasible and easy to perform.
      Compared with the buccal mucosal graft the LMG seems to be associated with less
      postoperative pain and a minor risk of donor site complications. These
      preliminary functional and esthetic data are satisfactory.

PMID- 16407004
TI  - The prevalence of urinary incontinence among community dwelling adult women:
      results from the National Health and Nutrition Examination Survey.
AB  - PURPOSE: Population based studies estimate that a large proportion of adult women
      report urinary incontinence. However, there is a wide range of estimates of the
      burden posed by UI. To measure the prevalence of incontinence in women in the
      community we analyzed data from women responding to the National Health and
      Nutrition Examination Survey. MATERIALS AND METHODS: NHANES is a series of health
      and nutrition surveys performed by the National Center for Health Statistics.
      From 1999 to 2000 NHANES asked a national sample of community dwelling women, "In
      the past 12 months, have you had difficulty controlling your bladder, including
      leaking small amounts of urine when you cough or sneeze (exclusive of pregnancy
      or recovery from childbirth)?" Questionnaire results were recorded and analyzed
      with respect to demographic data including age, race and level of education.
      RESULTS: The overall prevalence of urinary incontinence in women was 38%. The
      prevalence of daily incontinence increased with age, ranging from 12.2% in women
      60 to 64 years old to 20.9% in women 85 years old or older. Of women reporting
      any incontinence, 13.7% reported daily incontinence, and an additional 10.3%
      reported weekly incontinence. Prevalence was higher in non-Hispanic white women
      (41%) than in non-Hispanic black (20%) or Mexican-American women (36%). Women
      with less than a high school education were less likely to report incontinence
      than were those with at least a high school education. CONCLUSIONS: Unlike many
      other studies the NHANES draws a nationally representative sample of subjects in
      the community and, thus, provides prevalence data for urinary incontinence for
      all women in the United States. Prevalence is high, and varies with age,
      race/ethnicity and socioeconomic variables.

PMID- 16407003
TI  - Is nocturia equally common among men and women? A population based study in
      Finland.
AB  - PURPOSE: We assessed the prevalence of nocturia and its association with
      sociodemographic factors. MATERIALS AND METHODS: Information was collected with a
      questionnaire mailed to a random sample of 6,000 subjects 18 to 79 years old,
      identified from the Finnish Population Register Centre. Nocturia was defined as 1
      or more, or 2 or more voids per night. Information was collected using the DAN
      PSS questionnaire with an additional question from the AUA-SI questionnaire. Age
      standardized prevalence was calculated using the European standard population.
      Logistic regression was used for multivariate analysis. RESULTS: Of the 6,000
      subjects 62.4% responded and 97.9% of the participants provided information on
      all nocturia questions. The age standardized prevalence of nocturia (1 or more
      voids per night) was 37% (95% CI 34%-40%) among men and 43% (95% CI 40%-46%)
      among women. With criterion of 2 or more voids per night prevalence was 12% (95%
      CI 10%-14%) for men and 13% (95% CI 11%-14%) for women. Women 18 to 49 years old
      had more nocturia than men. At 50 to 59 years old half of men and women reported
      nocturia. In older age groups nocturia was more frequent among men than women.
      The prevalence of nocturia increased at a constant rate with age. It increased
      twice as rapidly in men as among women (increase in OR 7.3% [95% CI 6.5%-8.2%]
      and 3.5% [95% CI 2.9%-4.1%] per year among men and women, respectively).
      CONCLUSIONS: The age standardized prevalence of nocturia (1 or more voids per
      night) was approximately 40% for both genders. In men the prevalence of nocturia
      increases more rapidly with age than in women. Nocturia is more common among
      women at a younger age but the differences disappear by middle age. In the
      elderly nocturia is more frequent among men.

PMID- 16407005
TI  - Comparison of the long-term outcomes between incontinent men and women treated
      with artificial urinary sphincter.
AB  - PURPOSE: We compared the long-term outcome of AUS between men and women who
      received the device for the management of stress urinary incontinence. MATERIALS
      AND METHODS: Between August 1983 and January 2004, 126 consecutive patients
      received the AUS AMS 800 at our center placed by the senior author (ACD). Of
      these patients 108 (53 men, 55 women) and 168 devices (88 in men, 80 in women)
      were available for review. Outcome measures include complications, duration and
      etiology of AUS failure, and satisfactory continence. RESULTS: Mean followup was
      8.1 +/- 5.6 years. Of the 108 patients 18 (40%) men and 31 (56%) women had no
      complications (p = 0.09). Of the 168 devices 76 (45%) eventually failed (44 or
      50% in men, 32 or 40% in women, p = 0.19). The incidences of failed device
      classified as mechanical, nonmechanical or iatrogenic were not significantly
      different (p = 0.07). Median device durations were 6.9 and 11.2 years in men and
      women, respectively (p = 0.002). Satisfactory continence was achieved in 82% of
      patients, in 43 (81%) men and in 46 (84%) women (p = 0.73), including 5 (9%) men
      and 35 (64%) women who were dry (0 pads, p = 0.01), 28 (53%) men and 4 (7%) women
      who wear 1 pad (p = 0.01), and 10 (19%) men and 7 (13%) women who use 2 pads per
      day. CONCLUSIONS: There were no differences in overall satisfactory continence
      and device failure rates. However, women have a higher dry rate (0 pad use) and
      longer functioning device duration compared to their male counterparts.

PMID- 16407006
TI  - Long-term durability of the distal urethral polypropylene sling procedure for
      stress urinary incontinence: minimum 5-year followup of surgical outcome and
      satisfaction determined by patient reported questionnaires.
AB  - PURPOSE: We report on the long-term outcomes of the distal urethral polypropylene
      sling. MATERIALS AND METHODS: We performed a prospective study of all consecutive
      patients who underwent a distal urethral polypropylene sling procedure between
      November of 1999 and April of 2000 for treatment of SUI. Surgical outcome was
      determined by patient self-assessment, and included symptom, bother and quality
      of life questionnaires. Physicians were blinded to patient responses. All
      patients had a minimum 5-year followup. Every patient treated was included in
      reporting outcomes in the intent to treat analysis. RESULTS: There were 69
      patients treated a minimum of 5 years before the analysis. Cases lost to followup
      were defined as treatment failures. At a minimum followup of 5 years patient
      determined subjective success rate was 88%. More than 5 years after surgery 72%
      of patients reported no symptoms of SUI and 74% reported never being bothered by
      SUI. Patients reported an overall mean improvement of symptoms of 81%, and
      quality of life due to urinary symptoms between pleased and mostly satisfied.
      CONCLUSIONS: The distal urethral polypropylene sling procedure has low morbidity
      and excellent durability in treating patients with SUI.

PMID- 16407007
TI  - Prospective, randomized comparison of ureteroscopic endopyelotomy using
      holmium:YAG laser and balloon catheter.
AB  - PURPOSE: We compared the safety and efficacy of the 2 retrograde endopyelotomy
      techniques. MATERIALS AND METHODS: A prospective study was done from January 2001
      to October 2003. Preoperative radiological evaluation included excretory
      urography, multiphasic helical computerized tomography and diuretic renography.
      Exclusion criteria were marked hydronephrosis, ipsilateral renal function less
      than 25% and renal stones or a significant crossing vessel at the ureteropelvic
      junction. Eligible patients were randomized to ureteroscopic laser endopyelotomy
      and retrograde Acucise endopyelotomy (20 per group). UPJ obstruction was primary
      in 14 patients and secondary in 26. The ureteropelvic junction was incised in the
      lateral direction and an endopyelotomy Double-J stent (Medical Engineering Corp.,
      New York, New York) was left for 6 weeks. Subjective and objective outcomes were
      evaluated 3 and 6 months after stent removal, and every 6 months thereafter.
      RESULTS: Mean operative time +/- SD was comparable in the laser and Acucise
      groups (64.7 +/- 22.4 and 58.7 +/- 20.2, respectively). The overall complication
      rate in the Acucise group was more than in the laser group (25% vs 10%). At a
      mean followup of 29.9 +/- 10.8 months (range 6 to 48) the laser group showed a
      higher success rate than the Acucise group (85% vs 65%) but the difference in the
      complication and success rates was not statistically significant. CONCLUSIONS:
      Despite the advanced endourological skills required for ureteroscopic laser
      endopyelotomy its safety and efficacy seem to be better than those of Acucise
      endopyelotomy. However, a larger number of patients is needed to confirm these
      findings.

PMID- 16407009
TI  - A prospective study of symptoms and quality of life in men with chronic
      prostatitis/chronic pelvic pain syndrome: the National Institutes of Health
      Chronic Prostatitis Cohort study.
AB  - PURPOSE: We present the results of 2 years of symptom and quality of life
      followup of men with CP/CPPS enrolled in the CPC. MATERIALS AND METHODS: We
      followed 445 subjects from 6 clinical centers across North America for 2 years
      with outcome measures that included the NIH-CPSI, quality of life, and GRA. All
      subjects were treated according to usual care practices at each clinical site.
      RESULTS: Of the 445 subjects 293 had complete data at 2 years. Withdrawals were
      younger, had been diagnosed more recently and had higher baseline symptoms. Among
      the 293 men the mean improvement at 2 years was 5 points on the 43-point NIH-CPSI
      total score. Most of the observed improvement occurred in the first 3 months of
      followup. Among all 445 subjects, retaining withdrawals in the denominator, 31%
      considered themselves moderately or markedly improved at 2 years. Although group
      mean symptom scores were stable and improved slightly over time, some individual
      subjects reported large fluctuations. No baseline demographic or clinical factors
      significantly predicted changes in symptom scores over time. CONCLUSIONS: CP/CPPS
      is a chronic disease characterized by substantial variation in symptoms within
      and among subjects. There is no evidence that the disorder worsens significantly
      during 2 years of followup, and for about a third of men with long-standing
      symptoms there may be moderate to marked improvement during this period.

PMID- 16407013
TI  - Arterial anastomosis without sutures using ring pin stapler for clinical renal
      transplantation: comparison with suture anastomosis.
AB  - PURPOSE: The metal ring pin stapler was initially developed for microvascular
      surgery and there has been little experience of their use in larger vessels. We
      determined if the titanium ring pin coupling system could be safely and rapidly
      applied for arterial reconstruction in clinical renal transplantation. MATERIALS
      AND METHODS: The donor renal artery was end-to-end anastomosed to the internal
      iliac artery with titanium ring pin staplers in 36 patients. Anastomotic, clamp
      and total operative time and vascular problems were compared with those in the
      control group of sutured anastomosis in 39 transplant recipients. RESULTS: The
      completion of mechanical anastomosis required half the time of suture
      anastomosis. Mean clamp time was 17.8 minutes in the nonsuture group and 28.1
      minutes in the control group. There was no significant difference in total
      operative time between the 2 groups. A small anastomotic line leak was noted in
      each group, which was temporary and self-limited. There were no postoperative
      anastomotic failures, postoperative bleeding episodes or need to revise the
      anastomosis (100% patency rate) in the 2 groups. Of the patients 61 were followed
      for 2 to 5 years. Transplant renal artery stenosis was observed in 1 patient in
      the nonsuture group but 3 in the control group. CONCLUSIONS: The anastomotic
      technique with the ring pin system is safe and simple, permitting an expeditious
      and everting anastomosis with a smooth intima-to-intima junction. Application of
      this technique may decrease warm ischemia time and the incidence of anastomotic
      artery stenosis, thus, improving outcomes.

PMID- 16407011
TI  - Age, comorbidity and hypertensive co-medication do not affect cardiovascular
      tolerability of 10 mg alfuzosin once daily.
AB  - PURPOSE: We assessed in real-life practice the impact of age, cardiovascular
      comorbidity and co-medication on the tolerability and efficacy of 10 mg alfuzosin
      OD in men with lower urinary tract symptoms suggestive of benign prostatic
      obstruction. MATERIALS AND METHODS: A total of 6,523 men with a mean age of 64.7
      years were enrolled in a 6-month open label study of 10 mg alfuzosin OD. They
      were stratified by age quartile (younger than 60, 60 to 64, 65 to 70 and older
      than 70 years), comorbidity (hypertension, ischemic heart disease and diabetes)
      and antihypertensive co-medication (diuretics, beta-blockers, angiotensin
      converting enzyme inhibitors, angiotensin II inhibitors and calcium channel
      antagonists). RESULTS: Alfuzosin was effective and well tolerated. Despite an
      increased prevalence of cardiovascular comorbidity and antihypertensive co
      medication with age changes in blood pressure did not significantly differ among
      age groups. In controls, ie those with no cardiovascular comorbidity or co
      medication, alfuzosin produced minimal decreases in sitting systolic (mean -2.6
      to -2.8 mm Hg) and diastolic (mean -1.7 to -1.8 mm Hg) blood pressure. In men
      with cardiovascular comorbidity mean decreases in systolic (-3.5 to 5.8 mm Hg)
      and diastolic (-2.0 to -3.3 mm Hg) blood pressure remained marginal. Of the 6,523
      exposed patients 19.3% withdrew from the study, mainly for adverse events (6.4%)
      or a lack of efficacy (5.3%), while 229 (3.5%) experienced serious adverse events
      and 1,558 (23.9%) reported at least 1 treatment emergent adverse event. The most
      commonly reported adverse event was dizziness/postural dizziness (4.8%).
      Hypotension/postural hypotension was uncommon (0.7%). Age, cardiovascular
      comorbidity and antihypertensive co-medication had no impact on the safety
      profile of 10 mg alfuzosin OD. CONCLUSIONS: Alfuzosin (10 mg) OD is effective and
      well tolerated, and it has marginal effects on blood pressure, including in
      elderly patients and those with hypertension, ischemic heart disease or diabetes
      and those receiving antihypertensive agents.

PMID- 16407015
TI  - Ischemia-reperfusion injury in cadaveric nonheart beating, cadaveric heart
      beating and live donor renal transplants.
AB  - PURPOSE: Ischemia-reperfusion injury is gaining importance in transplantation as
      being responsible for allograft dysfunction. Ischemia occurs during kidney
      procurement, which is shortest in LDs, and prolonged in cadaveric HBDs and NHBDs.
      MATERIALS AND METHODS: Renal transplants from 17 LDs, 15 HBDs and 19 NHBDs were
      assessed during reperfusion for biochemical markers of ischemia-reperfusion
      injury and assessed clinically. Central venous blood sampling was assayed for
      free radicals using electron spin resonance and tissue injury biomarkers, namely
      lactate dehydrogenase, fatty acid binding protein, alanine aminopeptidase,
      lactate and total antioxidants. RESULTS: The return to stable renal function was
      more rapid in LD renal transplants, while recovery continued from 3 months after
      hospital discharge in NHBD renal transplants. Injury markers, such as lactate
      dehydrogenase, fatty acid binding protein, alanine aminopeptidase and lactate,
      were raised at the time of reperfusion, especially in NHBD renal transplants.
      Free radical release measured by electron spin resonance showed 2 phase release,
      that is early (0 to 10-minute) and late (20 to 40-minute) release. In NHBD, HBD
      and LD renal transplants the index of free radical release in the early phase was
      1.43, 1.36 and 1.20, and in the late phase it was 1.43, 1.38 and 0.97,
      respectively (each ANOVA p <0.05). CONCLUSIONS: NHBD renal transplants were
      accompanied by a greater release of free radicals at reperfusion (NHBD > HBD >
      LD), which was associated with an increase in tissue injury markers at
      reperfusion. This was reflected in a slower return to stable renal function in
      NHBD compared to HBD and LD renal transplants.

PMID- 16407016
TI  - Recovery of abnormal ejaculation by intermittent tamsulosin treatment.
AB  - PURPOSE: We assessed the impact of intermittent tamsulosin treatment on abnormal
      ejaculation. MATERIALS AND METHODS: This prospective study was performed between
      January 2001 and December 2004. It included 405 patients who were at least 50
      years old with lower urinary tract symptoms. This study was divided into 2
      phases. In phase 1 patients received a 0.4 mg tamsulosin capsule daily after
      breakfast for at least 3 months. The second phase of this study was performed in
      the 30 patients with abnormal ejaculation. In this phase these patients received
      0.4 mg tamsulosin once daily every other day. Patients were assessed at study
      entry and at study week 6. RESULTS: Abnormal ejaculation was reported as
      retrograde ejaculation by 18 patients, as decreased volume by 7 and as absent
      ejaculate by 5. Ejaculatory function recovered during intermittent tamsulosin
      treatment in 12 patients with retrograde ejaculation and in 7 with decreased
      volume or absent ejaculate. As a result, 19 of 30 patients (63.3%) with abnormal
      ejaculation recovered. A significant improvement in retrograde ejaculation was
      found after intermittent tamsulosin treatment (p = 0.02). Although there were
      improvements in decreased volume or absent ejaculate at week 6 of intermittent
      treatment, these differences were not statistically significant (p = 0.42 and
      0.61, respectively). CONCLUSIONS: The results of the current study, which to our
      knowledge is the first report of the effect of intermittent tamsulosin treatment
      on abnormal ejaculation, show that this treatment modality is well tolerated and
      provides comparable improvements for abnormal ejaculation.

PMID- 16407018
TI  - Prevalence and risk factors for female sexual dysfunction in Turkish women.
AB  - PURPOSE: We assessed the prevalence of and risk factors for FSD using the Turkish
      version of the FSFI in Turkish women. MATERIALS AND METHODS: The study consisted
      of 518 women 18 to 55 years old living in Ankara, who completed the FSFI for the
      evaluation of FSD. The women were divided into 3 groups according to age, that is
      18 to 30 (273), 31 to 45 (192) and 46 to 55 years (53). Demographic
      characteristics and risk factors were assessed in all women. Findings were
      compared between women with and without FSD. RESULTS: According to the FSFI score
      48.3% of women reported FSD (FSFI score less than 25). The prevalence of FSD was
      41% at ages 18 to 30 years, 53.1% at ages 31 to 45 years and 67.9% at ages 46 to
      55 years. FSD was detected as a desire problem in 48.3% of women, an arousal
      problem in 35.9%, a lubrication problem in 40.9%, an orgasm problem in 42.7%, a
      satisfaction problem in 45.0% and a pain problem in 42.9%. Risk factors for FSD
      were age, smoking (OR 2.4, 95% CI 6.8 to 18.1), menopause (OR 1.7, 95% CI 2.7 to
      10.2), diet (OR 1.2, 95% CI 1.9 to 5.5) and marital status (OR 0.8, 95% CI 1.5 to
      3.2) (each p <0.001). CONCLUSIONS: Overall 48.3% of women in our study had FSD
      according to the FSFI. Apart from age, the most important risk factors for FSD
      were smoking, diet based life-style changes, menopause status and marital status.

PMID- 16407020
TI  - Is bowel preparation before excretory urography necessary? A prospective,
      randomized, controlled trial.
AB  - PURPOSE: A prospective, randomized, single blind, controlled trial was performed
      to determine whether routine bowel preparations are necessary for satisfactory
      visualization of the urinary system during IVP and compare the side effects of
      several bowel preparation methods. MATERIALS AND METHODS: A total of 200 patients
      between 17 and 70 years old at the outpatient department who were prescribed IVP
      were enrolled in this prospective study. Patients were divided into 4 groups and
      randomly received liquid supper, senna, magnesium sulfate solution and PEG-ELS as
      bowel preparation before IVP. Control and contrast images were assessed by a
      radiologist and a urologist blinded to the bowel preparation. IVP was given a
      visualization score, a fecal residue score, a bowel gas score and an overall
      quality score. Images were also divided into anatomical sections to assess
      visualization, and the effect of fecal residue and bowel gas. Questionnaires were
      prepared about the side effects of bowel preparation. RESULTS: For contrast
      images there was no significant difference in terms of visualization,, fecal
      residue, bowel gas and overall quality scores among the 4 groups. The same result
      was seen on the control image except for fecal residue scores, when the senna and
      PEG-ELS groups had a lower fecal residue score than the liquid supper group (p =
      0.001). Interestingly when considering sectional images, the right renal region
      of the control image showed that the senna and PEG-ELS groups had better
      visualization scores with less bowel gas and fecal residue than the liquid supper
      only group. Patients in all 3 laxative bowel preparation groups except the liquid
      supper group reported side effects. There was no statistically significant
      difference among these 3 groups in the attitude toward ingesting laxatives again.
      CONCLUSIONS: Our results suggest that routine bowel preparation prior to IVP does
      not improve the visibility or overall quality of control or contrast images,
      while patients experience certain side effects due to the bowel preparation. The
      laxative bowel preparation may be helpful only when visualizing the right renal
      region on the control image.

PMID- 16407022
TI  - Use of nephrectomy at select medical centers--a case of follow the crowd?
AB  - PURPOSE: Regionalization of high risk surgical procedures to larger, teaching
      hospitals has been suggested as a means to improve the quality of care. We
      determined the extent to which the regionalization of nephrectomy has occurred
      and describe the potential causes and implications of any observed
      regionalization. MATERIALS AND METHODS: The Nationwide Inpatient Sample comprises
      a 20% sampling of hospital discharges in the United States yearly. Patients
      undergoing nephrectomy for kidney cancer between 1988 and 2002 were identified
      using International Classification of Disease, Ninth Revision, Clinical
      Modification codes. Regionalization was assessed using 6 structural hospital
      measures, including teaching status, urban location, discharge volume,
      nephrectomy volume, bed capacity and for-profit status. Adjusted models were
      developed to identify the significance of temporal trends in each regionalization
      measure. RESULTS: We identified 66,621 patients undergoing nephrectomy during the
      study period. Compared to procedures performed between 1988 and 1990 the
      likelihood of undergoing nephrectomy at teaching, high nephrectomy volume and
      high throughput (all diagnoses) hospitals increased by 2.0 (CI 1.9 to 2.2), 7.4
      (CI 7.1 to 7.7) and 2.2 times (CI 2.1 to 2.2), respectively, in 2000 to 2002.
      Conversely nephrectomy was less likely to be performed at for-profit hospitals
      (OR 0.5, CI 0.5 to 0.6). Patients were more likely to undergo partial nephrectomy
      at teaching, high volume, high throughput, urban hospitals. CONCLUSIONS:
      Regionalization of nephrectomy to teaching and high volume (nephrectomy and all
      diagnoses) hospitals is currently under way. Although the implications are not
      entirely clear, this study provides further evidence for the crowding of complex
      surgical procedures into these institutions.

PMID- 16407025
TI  - Pediatric robot assisted laparoscopic dismembered pyeloplasty: comparison with a
      cohort of open surgery.
AB  - PURPOSE: We assessed the usefulness of RALP in children and compared an age
      matched cohort undergoing OPN to RALP for safety, efficacy, operative time, blood
      loss, in-hospital narcotic use and LOS. MATERIALS AND METHODS: We performed a
      retrospective case-control study from 2000 to 2004 of 33 patients undergoing RALP
      and 33 undergoing OPN. Average age of each group was not significantly different
      (RALP 7.8 years vs OPN 7.6 years, p = 0.75). Mean followup of RALP and OPN groups
      was 10 and 21 months, respectively. RESULTS: Etiology of the obstruction was not
      significantly different. Mean operative time was significantly less for OPN (181
      minutes vs 219 minutes for RALP, p = 0.031). As RALP experience increased,
      operative times improved and approached the OPN experience. RALP complications
      included 1 patient requiring reoperative surgery vs no complications in the OPN
      group (p = 0.15). Patients undergoing RALP had a mean LOS of 2.3 days compared to
      3.5 days for OPN (p <0.001). Total narcotic requirements were significantly less
      in the RALP group (p = 0.001). All patients in the OPN and 31 in the RALP group
      had either resolution of hydronephrosis, improvement in drainage or relief of
      symptoms. CONCLUSIONS: We documented the safety and efficacy of RALP in children.
      RALP showed advantages of decreased hospital stay, decreased narcotic use and
      operative times approaching those of open surgery. RALP is an option for
      pyeloplasty, and as robotic technology improves, this method of repair may become
      the minimally invasive treatment of choice.

PMID- 16407023
TI  - Duplex collecting system diagnosed during the first 6 years of life after a first
      urinary tract infection: a study of 63 children.
AB  - PURPOSE: We determined the prevalence, anatomical variants and coexisting
      complications of duplex collecting systems in children with a history of UTI.
      Additionally, we compared the prevalence and severity of the coexisting anomalies
      with those found in single systems. MATERIALS AND METHODS: We reviewed the
      records of children younger than 6 years who were evaluated following a first UTI
      during a 9-year period to identify those with duplex systems. Children without
      duplication anomalies comprised the control group. RESULTS: Of 774 evaluated
      children 63 (8%), more commonly females than males, had duplex systems. CDS were
      as common as IDS. VUR was the most commonly associated anomaly, with a higher
      prevalence in CDS (66%) and IDS (47%) compared to single systems (26%, p <0.0001
      and p = 0.007, respectively). Ectopic ureterocele, which was the second most
      common associated anomaly, was found in 20% of the CDS but in none of the IDS or
      single systems. The occurrence of renal scarring was similar among CDS, IDS (13%)
      and single systems (10%). Poorly functioning pole moieties occurred more often in
      CDS (40%) compared to IDS (4%, p = 0.003), and were observed in none of the
      single systems. The resolution rate of reflux tended to be higher in IDS compared
      to CDS. CONCLUSIONS: CDS were a common finding among children with UTI who had
      duplication anomalies. Although CDS and IDS were accompanied by VUR more often
      than were single systems, CDS were associated more often with severe VUR, other
      serious complications and poor renal function.

PMID- 16407027
TI  - Laparoscopic transabdominal pyeloplasty in children is feasible irrespective of
      age.
AB  - PURPOSE: We assessed the feasibility of laparoscopic transabdominal dismembered
      pyeloplasty in 46 infants and children with regard to patient age. MATERIALS AND
      METHODS: A total of 46 consecutive infants and children (31 male and 15 female)
      underwent laparoscopic transabdominal dismembered pyeloplasty using a 3 to 4
      trocar technique. All patients had confirmed unilateral deterioration of renal
      function on isotope renography. The 46 patients were divided into 3 age groups--1
      to 12 months (group 1, 14 patients), 1 to 7 years (group 2, 15 patients) and 7 to
      18 years (group 3, 17 patients). Followup included clinical and ultrasound
      assessment, and isotope renography at 3 months. RESULTS: Laparoscopic pyeloplasty
      was feasible in 44 of 46 patients (96%). Mean operative time was 175 minutes
      (range 120 to 270). The operation was converted due to impracticality of stenting
      the PUJ in 1 patient, and due to bleeding in 1. Mean operative time in 44
      successful laparoscopic procedures was not significantly different among the 3
      age groups (171 minutes in group 1, 169 minutes in group 2 and 173 minutes in
      group 3). Two patients required operative intervention for PUJ leakage, and 1
      underwent percutaneous nephrostomy with a further uneventful course. Mean
      followup was 29 months (range 3 to 86). A total of 44 patients (96%) were
      asymptomatic and had improved PUJ drainage on isotope renography. Two patients
      underwent redo pyeloplasty due to recurrent hydronephrosis at 1 month and 2
      years. CONCLUSIONS: Laparoscopic transabdominal dismembered pyeloplasty is
      effective and safe in infants and children. The feasibility is also excellent in
      patients younger than 1 year. The transabdominal approach revealed good
      exposition without a disadvantage for the patient.

PMID- 16407028
TI  - A novel technique for approximation of the symphysis pubis in bladder exstrophy
      without pelvic osteotomy.
AB  - PURPOSE: We evaluated the outcome of pubic bone approximation and internal
      fixation using a miniature metal plate and screws without osteotomy in children
      with bladder exstrophy. MATERIALS AND METHODS: A total of 17 children with
      bladder exstrophy underwent surgery. Mean patient age was 27 months. Of the
      patients 15 had a history of 1 or more failed bladder closures with or without
      osteotomy. All children underwent bladder closure and complete posterior and
      anterior urethroplasty with bladder neck wrap. Both ureteral orifices were
      brought together by the Gil-Vernet antireflux procedure. The pubes were brought
      together with 3 deeply placed 1 mm polyglactin sutures through the bone and fixed
      by placing a miniature metal plate with 6 to 7 screws. Patients remained in a
      frog leg bandage for 1 to 3 weeks. The plate was removed during additional
      surgery. Median followup was 61 months (range 14 to 71). RESULTS: All children
      had an uneventful postoperative period without any serious complications, except
      for skin erosion caused by a screw without bone infection in 1 patient, and
      miniature plate subluxation following cystoscopy for reinsertion of urethral
      catheter 3 days after initial surgery in 1. Operating time and hospital stay were
      significantly lower than in children undergoing osteotomy or Bryant's traction.
      Overall continence rate was 53.8%. CONCLUSIONS: Although the number of patients
      is low, these results are promising. Pubic bone adaptation with miniature plate
      fixation without any type of osteotomy or leg traction is safe and less invasive
      than bilateral osteotomy and postoperative leg traction or plaster.

PMID- 16407031
TI  - Midline dorsal plication to repair recurrent chordee at reoperation for
      hypospadias surgery complication.
AB  - PURPOSE: Midline dorsal plication is an efficient and safe surgical technique to
      correct chordee. We investigated the efficacy of midline dorsal plication for
      recurrent chordee in complicated hypospadias reoperations. MATERIALS AND METHODS:
      We retrospectively evaluated the charts of 25 boys who underwent reoperation
      between 1999 and 2004 due to complications of primary hypospadias repair other
      than meatal stenosis. A total of 15 cases were initially managed elsewhere for
      primary repair or complications. The etiology of recurrent chordee was defined at
      surgical correction. When recurrent chordee was noted a midline dorsal plication
      was performed. RESULTS: Of 25 patients 10 had previously undergone chordee
      repair. Nine of these patients were observed to have recurrent chordee and 1 had
      de novo chordee. A total of 10 patients had recurrent or delayed onset chordee.
      Mean patient age at primary repair was 6.28 years (range 1 to 33). Mean age at
      last operation for chordee was 15.9 years (range 4 to 66). Mean interval to
      recurrent chordee was 6 years (range 1 to 16), excluding a 66-year-old blind
      patient who did not know when recurrent chordee developed. Five patients had
      chordee recur before puberty at a mean interval of 2.6 years. Mean reoperation
      rate was 2.4 for recurrent chordee cases and 2.6 for chordee-free cases. Mean
      followup after midline dorsal plication for recurrent chordee repair was 22
      months (range 8 to 56), while mean followup in pubertal and postpubertal cases
      was 20 months. No recurrence of chordee or surgery related morbidity was observed
      after recurrent chordee repair by midline dorsal plication. CONCLUSIONS: Chordee
      may recur during puberty following successful chordee repair. The midline dorsal
      plication technique is simple, efficient and safe even in patients who have
      undergone multiple surgeries for hypospadias and chordee repair.

PMID- 16407033
TI  - Ultrasound assessment of detrusor thickness in children and young adults with
      myelomeningocele.
AB  - PURPOSE: We determine by ultrasonography the range of dT in carefully treated and
      followed children with myelomeningocele, and evaluate the role of such
      measurements for the understanding of bladder abnormalities in these patients.
      MATERIALS AND METHODS: We studied 66 children and young adults with MMC (34 males
      and 32 females, median age 8.1 years, range 1.1 to 20.1). Detrusor thickness was
      measured with a previously established ultrasonographic technique and the results
      were compared to those in normal children. The variation in detrusor thickness
      with degree of bladder dysfunction as well as with bladder wall trabeculation,
      kidney function and anticholinergic treatment was studied. RESULTS: The detrusor
      of the ventral wall was slightly thinner in children with MMC compared to normal.
      No significant variation in dT was found for different degrees of bladder
      dysfunction, bladder wall trabeculation, kidney function or anticholinergic
      treatment. Boys had thicker detrusor of the ventral wall than girls. CONCLUSIONS:
      Children with MMC, followed closely and treated according to international
      standards, do not acquire detrusor thickening as measured by ultrasonography. The
      detrusor thickness did not correlate with the degree of bladder dysfunction or
      renal function, or with anticholinergic treatment. Bladder wall trabeculation at
      VCU was not associated with bladder wall thickening on ultrasonography. We
      postulate that in a closely monitored and actively treated population of patients
      with MMC muscular hypertrophy and the development of connective tissue in the
      bladder wall is kept to a minimum.

PMID- 16407035
TI  - The treatment of catheterizable stomal incontinence with endoscopic implantation
      of dextranomer/hyaluronic acid.
AB  - PURPOSE: The creation of a catheterizable stoma has revolutionized the management
      of complex bladder reconstruction. Unfortunately, urinary incontinence per
      catheterizable stoma is seen in some patients. We present our experience with the
      use of submucosal implantation of dextranomer/hyaluronic acid in patients with
      catheterizable stomas with urinary incontinence. MATERIALS AND METHODS: A total
      of 14 patients 9 to 49 years old (mean age 17.8) underwent submucosal
      implantation of dextranomer/hyaluronic acid for incontinence of catheterizable
      stoma at our institutions between October 2001 and March 2004. RESULTS: There
      were 9 males and 5 females. Type of bowel for stoma creation included 12
      appendixes and 2 small bowels. All patients had significant leak per stoma and
      were candidates for revision. The dextranomer/hyaluronic acid volume injected
      ranged from 2 to 6 cc (mean 3.7). A total of 10 patients were dry after 1
      injection, 1 was dry after 2 injections and 3 remained incontinent after the
      procedure. Our success rate was 79%. CONCLUSIONS: Our initial experience with the
      endoscopic treatment of incontinence of catheterizable stoma is encouraging, with
      a 79% success rate. We believe that this minimally invasive approach is warranted
      as an initial step in the management of urinary incontinence of catheterizable
      stoma before undertaking more challenging procedures.

PMID- 16407036
TI  - Dextranomer/hyaluronic acid for vesicoureteral reflux: success rates after
      initial treatment failure.
AB  - PURPOSE: Following Food and Drug Administration approval of Dx/HA there has been
      increasing interest in the endoscopic management of VUR. Currently, there are few
      data regarding the success rates of repeat injection. We recently published our
      success rates for a group of children following initial Dx/HA treatment, and
      herein report the success rate of a subgroup of children undergoing repeat
      injection. MATERIALS AND METHODS: We queried our database to identify all
      children undergoing a second Dx/HA injection for the treatment of VUR at our
      institution. VUR grades as determined by VCUG before and after the second
      treatment were specifically noted. Success was defined as the complete absence of
      VUR by VCUG. RESULTS: A total of 42 children (37 girls and 5 boys) with a mean
      age of 5 years underwent a second Dx/HA treatment for VUR after initial treatment
      failure. Complete followup was available for 39 patients (53 ureters). Before the
      second injection 14 patients had bilateral and 25 had unilateral VUR, with a mean
      grade of 2.2. A second Dx/HA injection resolved VUR in 35 of 39 patients (90%)
      and in 47 of 53 ureters (89%). A second injection resolved reflux in 7 of 8
      ureters (88%) with grade I, 24 of 26 (92%) with grade II and 16 of 19 (84%) with
      grade III VUR. CONCLUSIONS: A second Dx/HA injection for the treatment of VUR
      persisting after initial endoscopic treatment has a high success rate. This
      information is useful when counseling parents after initial treatment failure.

PMID- 16407037
TI  - Endoscopic therapy for vesicoureteral reflux: a meta-analysis. I. Reflux
      resolution and urinary tract infection.
AB  - PURPOSE: Current American Urological Association treatment guidelines for
      vesicoureteral reflux do not include any recommendations pertaining to endoscopic
      therapy (subureteral injection of bulking agent). We performed a meta-analysis of
      the existing literature pertaining to endoscopic treatment to allow comparison
      with reports of open surgical correction. MATERIALS AND METHODS: We searched all
      peer reviewed articles published through 2003 pertaining to endoscopic treatment
      of vesicoureteral reflux. A total of 63 articles were double reviewed by 9
      pediatric urologists, and the data were tabulated on data retrieval sheets. A
      mixed effects logistic regression model was used to obtain overall estimates of
      event probabilities (eg reflux resolution, ureteral obstruction) together with
      their 95% confidence intervals. Individual study estimates were obtained with
      overall estimate and observation characteristics using empirical Bayes
      calculations. Differences between or among specific groups were assessed using
      the F-test. RESULTS: The database included 5,527 patients and 8,101 renal units.
      Following 1 treatment the reflux resolution rate (by ureter) for grades I and II
      reflux was 78.5%, grade III 72%, grade IV 63% and grade V 51%. If the first
      injection was unsuccessful, the second treatment had a success rate of 68%, and
      the third treatment 34%. The aggregate success rate with 1 or more injections was
      85%. The success rate was significantly lower for duplicated (50%) vs single
      systems (73%), and neuropathic (62%) vs normal bladders (74%). The success rate
      was similar among children and adults. Following a previous failed open
      reimplantation endoscopic treatment was successful in 65% of patients. After
      endoscopic treatment with variable followup pyelonephritis developed in 0.75% of
      patients and cystitis in 6%. There were few reports of renal scarring following
      treatment. CONCLUSIONS: Endoscopic treatment provides a high rate of success in
      children with reflux that decreases with increasing grade, although multiple
      treatments may be necessary. Future reports of endoscopic therapy should include
      rates of urinary tract infection and renal scarring.

PMID- 16407038
TI  - Loratadine exerts estrogen-like effects and disrupts penile development in the
      mouse.
AB  - PURPOSE: Hypospadias is a developmental anomaly of the penis and urethra that can
      be steroid mediated. It is characterized by a urethral opening occurring below
      the normal location at the tip of the penis. The link between loratadine, the
      active ingredient in a common over-the-counter antihistamine, and hypospadias,
      the most common congenital abnormality, has been the subject of controversy. We
      examined the effect of in utero exposure to an over-the-counter loratadine syrup
      on urethral development, and expression of androgen and estrogen receptors.
      MATERIALS AND METHODS: We orally gavaged pregnant dams with the equivalent of a
      daily dose of loratadine syrup, with 3 times that dose or with a corn oil gavage
      control from GD 12 through GD 17. Using gross and histological assessment and 3D
      reconstruction, we looked for urethral abnormalities in fetal GTs at E 19. We
      also used real-time quantitative PCR to characterize the expression levels of
      steroid receptor mRNA in the GT at E 19, a critical stage for completion of
      urethral and penile development in this species. RESULTS: Loratadine syrup
      disrupted normal urethral development in the mouse, based on gross morphology and
      histological assessment, and also disrupted steroid receptor expression,
      producing an expression profile similar to that resulting from in utero exposure
      to ethinyl estradiol. CONCLUSIONS: In utero exposure to over-the-counter
      loratadine syrup can result in hypospadias in this model, and creates changes in
      the steroid receptor mRNA expression profile similar to those elicited by a
      synthetic estrogen.

PMID- 16407039
TI  - Juxtaglomerular cell tumor of the kidney.

PMID- 16407040
TI  - Renal rupture in a preeclamptic patient with subsequent abscess.

PMID- 16407041
TI  - Pulsed cavitational ultrasound: a noninvasive technology for controlled tissue
      ablation (histotripsy) in the rabbit kidney.
AB  - PURPOSE: The optimal minimally invasive treatment for small renal masses
      continues to evolve. Current ablative technologies rely on thermal mechanisms for
      tissue destruction. However, the creation of precise lesions is limited by
      inhomogeneous heating/cooling due to tissue variability, perfusion effects and
      tissue charring. We hypothesized that nonthermal mechanical effects of ultrasound
      (cavitation) can be used to progressively homogenize tissue in controlled fashion
      with predictable results. MATERIALS AND METHODS: We developed a focused annular
      array ultrasound system capable of delivering high intensity (greater than 20
      kW/cm) short pulses (20 microseconds) of energy to a target volume. This system
      operates at a repetition frequency of 100 Hz, resulting in a low time averaged
      power output (approximately 5 W total acoustic output). Following approval from
      the institutional animal care committee a series of transcutaneous ablations were
      performed in the normal kidneys of 10 rabbits. RESULTS: Lesions created with a
      small number of pulses (10 or 100) produced scattered areas of damage
      characterized by focal hemorrhage and small areas of cellular injury in the
      targeted volume. Lesions created with greater numbers of pulses (1,000 or 10,000)
      demonstrated complete destruction of the targeted volume. Gross examination
      revealed that lesions contained a liquefied core with smooth walls and sharply
      demarcated boundaries. Histological examination demonstrated extensive areas of
      acellular debris surrounded by a narrow margin of cellular injury. CONCLUSIONS:
      This pulsed cavitational ultrasound system is capable of transcutaneous
      nonthermal destruction of renal tissue. Refinement of this technology for
      noninvasive ablation of small renal masses is currently under way.

PMID- 16407042
TI  - Involvement of ubiquitination and sumoylation in bladder lesions induced by
      persistent long-term low dose ionizing radiation in humans.
AB  - PURPOSE: We determined whether ubiquitination and sumoylation processes are up
      regulated in bladder urothelium by chronic, long-term, persistent low doses of
      ionizing radiation in male patients with benign prostate hyperplasia and females
      with chronic cystitis living more than 19 years in 137Cs contaminated areas after
      the Chernobyl accident in Ukraine. MATERIALS AND METHODS: Bladder urothelial
      biopsies from 45 patients were subjected to histopathological and
      immunohistochemical study of Ub, SUMO1, SUMO E2 conjugating enzyme Ubc9, and the
      cell cycle inhibitors p53 and p27(Kip1). RESULTS: Of 25 group 1 patients from
      radio contaminated areas chronic proliferative atypical cystitis (Chernobyl
      cystitis), featuring multiple foci of dysplasia, and carcinoma in situ were
      observed in 23 (92%) and 19 (76%), respectively, in addition to 1 small pTa grade
      1 urothelial carcinoma. Chronic cystitis with areas of dysplasia and urothelial
      hyperplasia were detected in 2 (10%) and 3 (15%), respectively of the 20 patients
      in control group 2 from clean (without radio contamination) areas of Ukraine.
      Greatly increased levels of Ub, SUMO1, Ubc9 and p53 as well as decreased levels
      of p27(Kip1) were evident in patients in group 1 compared to those in group 2
      (all p <0.001). CONCLUSIONS: These findings support the hypothesis that up
      regulated ubiquitination and sumoylation processes might be an adaptive response
      to unscheduled proteolysis of aberrant p53 and p27(Kip1) cell cycle regulators
      occurring with long-term low dose rate ionizing radiation exposure with a
      possible contribution to urothelial carcinogenesis.

PMID- 16407043
TI  - A preclinical study of prostate sentinel lymph node mapping with
      [99mTC]diethylenetetramine pentaacetic acid-mannosyl-dextran.
AB  - PURPOSE: SLN identification could improve the pathological staging of prostate
      cancer. Prior SLN studies have been compromised by delayed radiotracer uptake
      rates and significant diffusion rates out of the sentinel nodes. Lymphoseek is a
      new radiopharmaceutical specifically designed for SLN mapping. It shows rapid and
      sustained SLN uptake. MATERIALS AND METHODS: We investigated the use of
      Lymphoseek for prostate SLN mapping by measuring SLN uptake in 12 anesthetized
      pigs. The prostate was injected with 0.05 ml of a 1:1 volume per volume mixture
      of Lymphazurin and 1.0 mCi Lymphoseek (1 nmole). Within 5 to 19 minutes the
      pelvic lymph nodes were dissected and assayed with a gamma probe. A lymph node
      was considered a sentinel node if it had count rates that exceeded 10 times the
      background count. We calculated the percent of injected dose of each lymph node
      excised and the prostate gland. RESULTS: A total of 35 SLNs were identified in
      the 12 studies. Of the SLNs 81% were located outside of the obturator fossa in
      this pig model. The SLN percent of injected dose was 0.05% to 7.75% (mean +/- 1
      SD 1.74% +/- 1.92%). The mean percent of injected dose in the prostate was 27% +/
      12%. There was no correlation between the side of SLN and the lobe injected.
      CONCLUSIONS: After prostate administration of Lymphoseek pelvic SLNs attain high
      signal-to-background ratios within 10 minutes. This property should permit
      intraoperative injection and SLN mapping without significantly adding to the
      duration of prostatectomy. A phase I clinical trial has been initiated, which
      will later incorporate minimally invasive techniques.

PMID- 16407044
TI  - Uropathogenic Escherichia coli and tolerance to nitric oxide: the role of
      flavohemoglobin.
AB  - PURPOSE: NO has an important role as part of the innate host response against
      bacterial infections. Flavohemoglobin, which is encoded by the hmp gene, protects
      Escherichia coli against nitrosative stress. We compared the NO tolerance of UPEC
      and nonpathogenic strains, and examined the involvement of flavohemoglobin.
      MATERIALS AND METHODS: The E. coli K12 derivates HB101 and DH5alpha represent
      nonpathogenic strains, while J96 and IA2 represent UPEC strains. HB101 was used
      as the host for a pBR322 plasmid carrying the hmp gene. Bacterial tolerance to NO
      was evaluated by determining cfu. Flavohemoglobin expression was examined using
      Northern and Western blot analysis. RESULTS: In the stationary growth phase, J96
      was significantly more tolerant to DETA/NO (Alexis Biochemical, Lausen,
      Switzerland) (1 mM) compared to HB101 (47% +/- 11% vs 6.4% +/- 3.1% cfu). In the
      exponential growth phase DETA/NO exposure resulted in 98% +/- 4.6% cfu for J96
      and 74% +/- 7.6% cfu for IA2 compared to 15% +/- 5.9% for HB101 and 21% +/- 12%
      for DH5alpha. HB101 over expressing hmp showed increased tolerance to DETA/NO
      (0.5 mM) compared to WT HB101 (106% +/- 5.6% vs 67 +/- 6.2%, p <0.01). Northern
      and Western blot analysis demonstrated increased flavohemoglobin expression after
      DETA/NO exposure and the strongest expression in HB101 carrying hmp on a
      multicopy plasmid. CONCLUSIONS: UPEC strains were significantly more tolerant to
      DETA/NO than nonpathogenic strains, which suggests a correlation between
      virulence and NO tolerance. Flavohemoglobin expression increased after DETA/NO
      exposure in UPEC and in nonpathogenic strains.

PMID- 16407045
TI  - Tumor necrosis factor promotes differential trafficking of bladder mast cells in
      neurogenic cystitis.
AB  - PURPOSE: IC is often considered neurogenic cystitis, in which mast cells are
      involved in a positive feedback loop that results in sustained urothelial
      inflammation. To characterize these processes we developed a murine model of
      neurogenic cystitis using Bartha's strain of PRV based on a similar model in the
      rat. MATERIALS AND METHODS: Female C57BL/6 mice (National Cancer Institute,
      Bethesda, Maryland) were used in the study. Neurogenic cystitis was induced by
      the injection of Bartha's strain of PRV (2.2 x 10 pfu) into the abductor caudalis
      dorsalis tail base muscle. Bladder inflammation was assessed by leukocyte influx
      and Evans blue dye extravasation. Mast cells were visualized in bladder tissue by
      staining with 0.1% toluidine blue. RESULTS: Inoculation with PRV in the abductor
      caudalis dorsalis resulted in cystitis within 3 days. Coincident with the
      induction of cystitis mast cells accumulated in the lamina propria due to mast
      cell trafficking from the proximal detrusor (relative to the lumen), whereas mast
      cells from the distal detrusor were unchanged and total mast cell counts were not
      increased. Degranulated mast cells increased approximately 20-fold in the lamina
      propria of infected mice relative to controls. In TNF receptor 1/2 deficient mice
      (Jackson Laboratory, Bar Harbor, Maine) mast cell trafficking was not observed in
      response to PRV and mast cells were not degranulated. CONCLUSIONS: These data
      indicate that neurogenic cystitis is associated with the differential trafficking
      and activation of distinct mast cell pools in the bladder. Since TNF mediates
      these events, anti-TNF therapy may mitigate the pathogenesis of neurogenic
      cystitis.

PMID- 16407046
TI  - Interleukin-4 and 13 induce the expression and release of monocyte
      chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor
      smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor
      alpha.
AB  - PURPOSE: Interstitial cystitis is characterized by an increased number of
      activated MCs in the detrusor muscle. However, to our knowledge the factors that
      influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1,
      IL-6 and SCF have a critical role in the regulation of MC development, signaling
      and function. We investigated whether HDSMCs are capable of expressing and
      releasing MCP-1, IL-6 and SCF in response to IL-4, IL-13, IL-1beta and tumor
      necrosis factor-alpha. MATERIALS AND METHODS: HDSMCs were isolated and cultured
      using an explant technique. Protein expression, and the secretion of MCP-1, IL-6
      and SCF were assayed by semiquantitative reverse transcriptase-polymerase chain
      reaction and specific enzyme-linked immunosorbent assay. RESULTS: Unstimulated
      cells released low amounts of MCP-1, IL-6 and SCF. In cells stimulated by IL-4
      MCP-1 mRNA was up-regulated by a mean factor +/- SD of 3.5 +/- 1.3, IL-6 mRNA was
      up-regulated by 3.8 +/- 1.3, the soluble form of SCF was up-regulated by 3.2 +/-
      0.6 and the membrane bound form of SCF was up-regulated by 7.9 +/- 5.6. For IL-13
      stimulated cells the values were 2.6 +/- 1.5, 3.6 +/- 2.1, 2.9 +/- 1.6 and 5.7 +/
      3.7, respectively. Soluble SCF mRNA expression was 5 times higher than the
      expression of mSCF mRNA. IL-4 and IL-13 given separately stimulated MCP-1, IL-6
      and SCF secretion in a concentration (0.01 to 100 ng/ml) and time (0 to 24 hours)
      dependent manner. Furthermore, IL-1beta and tumor necrosis factor-alpha alone
      induced significant release of MCP-1, IL-6 and SCF but in combination with IL-4
      or IL-13 it induced greater secretion of MCP-1, IL-6 and SCF. CONCLUSIONS: To our
      knowledge these findings demonstrate for the first time that HDSMCs express and
      release MCP-1 and IL-6, and show relatively high expression of soluble SCF. This
      supports our hypothesis that HDSMCs may have an active role by orchestrating the
      local inflammatory response in the bladder wall with possible implications for
      the pathophysiology of detrusor mastocytosis.

PMID- 16407047
TI  - Why does the Bonn Risk Index discriminate between calcium oxalate stone formers
      and healthy controls?
AB  - PURPOSE: The BRI has been shown to discriminate between calcium oxalate stone
      formers and controls. BRI is the ratio of the concentration of ionized calcium
      and the amount of oxalate that must be added to 200 ml urine to initiate
      crystallization. Higher BRI values are predictive of being a stone former and a
      value of 1.0 has been found to be the cutoff value to distinguish stone formers
      and controls. It is not easy to present a consistent argument based on the
      thermodynamics of calcium oxalate crystallization to account for the success of
      this index. For instance, why should 2 samples sharing the same BRI but with
      different ionized calcium and oxalate values have the same likelihood of being
      obtained from a stone former? MATERIALS AND METHODS: Using data on 195 samples
      the distribution and interrelationships of measured variables were examined. They
      were used to calculate illustrative data with which it was possible to examine
      the effects of varying the parameters and their relationships. RESULTS: Data
      simulations identified 3 necessary and sufficient conditions that must be met for
      BRI to be an effective discriminator between stone former and nonstone former
      urine samples. CONCLUSIONS: The success of BRI can be explained as the natural
      outcome of there being significantly different distributions (stone formers vs
      nonstone formers) of the concentration of ionized calcium and the formation
      product minus activity product difference as well as the correlation between
      these 2 variables.

PMID- 16407048
TI  - Bladder volume alters cholinergic responses of the isolated whole mouse bladder.
AB  - PURPOSE: The isolated bladder expresses autonomous activity, which may contribute
      to the generation of lower urinary tract sensation or pathophysiology. We
      evaluated how the effect of a cholinergic agonist on autonomous activity alters
      with increasing volume and in the presence of substances known to modulate
      functional bladder capacity. MATERIALS AND METHODS: The bladder of 22 adult
      female C57 black mice were mounted in whole organ tissue baths. Recordings of
      intravesical pressure were performed under standardized conditions at different
      bladder volumes. RESULTS: At low volume the muscarinic agonist arecaidine
      elicited an initial peak response, which subsided to a sustained steady state
      pressure. At high volume phasic pressure fluctuations were also apparent. An M2
      receptor antagonist caused a significantly greater decrease in peak and steady
      state responses than in pressure fluctuations. An M3-receptor antagonist
      decreased all 3 components. Alpha, beta-methylene adenosine triphosphate markedly
      decreased fluctuations, in contrast to norepinephrine, which eliminated the
      steady state response while preserving fluctuations. CONCLUSIONS: The response to
      cholinergic stimulation of the isolated bladder has 3 components. The initial
      tonic peak response increases with bladder distention and it is inhibited by M2
      and M3 muscarinic receptor antagonists. The tonic steady state response does not
      vary with bladder volume and it is inhibited by M2 and M3-receptor antagonists,
      and by beta3-adrenergic receptor agonists. Phasic fluctuations are minimal at low
      bladder volume, and with alpha, beta-methylene adenosine triphosphate or an M3
      receptor antagonist. Thus, the response to cholinergic stimulation varies with
      bladder volume. It can be differentially modulated by muscarinic antagonists and
      also by agents acting through nonmuscarinic receptors.

PMID- 16407049
TI  - Partial bladder outlet obstruction induces urethral smooth muscle hypertrophy and
      decreased force generation.
AB  - PURPOSE: PBOO leads to increased urinary frequency, decreased void volume,
      hypertrophy of the detrusor SM, and alterations in contractile and regulatory
      proteins. This study was done to determine whether PBOO induced increases in
      urinary frequency and detrusor SM hypertrophy are associated with an alteration
      in the contractility and expression of myosin isoforms in urethral SM. MATERIALS
      AND METHODS: PBOO was surgically induced in male New Zealand White rabbits, and
      sham operated rabbits served as controls. After surgery, rabbits were kept 12
      days, and prior to sacrifice, urine output and voiding frequency were monitored
      by keeping the animals in metabolic cages for 24 hours. Animals with increased
      urinary frequency (mean +/- SEM 43 +/- 12 voids per 24 hours) and sham operated
      rabbits (6 +/- 3 voids per 24 hours) were used for this study. Morphology of the
      urethra was studied using light and immunofluorescence microscopy. The expression
      of myosin isoforms was analyzed at the mRNA and protein levels by RT-PCR and
      Western blotting. RESULTS: The urethral wall and SM of PBOO rabbits showed
      hypertrophy. The force produced by the longitudinal muscle strips of PBOO animals
      in response to phenylephrine, KCl, or electrical field stimulation was decreased
      50%, 37% and 40%, respectively. Immunofluorescence microscopy revealed a decrease
      in nerve density. RT-PCR and Western blotting showed a decrease in the expression
      of myosin isoform SM-B with a concomitant increase in SM-A at the mRNA and
      protein levels. CONCLUSIONS: Our data show hypertrophy of the urethral wall and
      SM, and alterations in contraction, innervation, and myosin isoforms in PBOO
      induced detrusor hypertrophy.

PMID- 16407050
TI  - Abnormal lung development precedes oligohydramnios in a transgenic murine model
      of renal dysgenesis.
AB  - PURPOSE: Renal development regulates prenatal lung growth by maintaining fetal
      urine output and liquor volume. However, shared signaling pathways underpinning
      renal and lung morphogenesis indicate that lung hypoplasia in the presence of
      renal dysgenesis may not result from oligohydramnios alone. We used a transgenic
      model of renal agenesis/anuria to test whether lung hypoplasia precedes any
      possible influence of oligohydramnios. MATERIALS AND METHODS: E12 lung primordia
      from normal and gamma1III4 deficient murine embryos (fetal anuria and renal
      agenesis-dysgenesis) were cultured for 72 hours. Morphological lung development
      was measured at 24, 48 and 78 hours by bud counting and tracings of lung
      epithelial contour using image analysis software and photomicrographs. Genotyping
      was performed by a separate blinded investigator. RESULTS: E12 homozygous mutant
      lungs branched but had significant decreases in bud count, epithelial area and
      perimeter compared to heterozygous or WT controls. These changes presented prior
      to oligohydramnios and persisted in isolation from the developing renal tract
      throughout the 72-hour culture period. CONCLUSIONS: Lethal lung hypoplasia seen
      at term in this model is present from the earliest stages of development,
      persists in vitro and, therefore, it is not consequent on renal dysfunction.
      These data implies that 1) fetal interventions for severe prenatal uropathies may
      have variable success for protecting future lung function and 2) patients with
      fetal uropathies may warrant greater scrutiny of prenatal lung growth and long
      term postnatal lung function.

PMID- 16407051
TI  - Re: Laparoscopic nephrectomy for Wilms tumor after chemotherapy: initial
      experience.

PMID- 16407052
TI  - Re: Bladder cancer risk following primary and adjuvant external beam radiation
      for prostate cancer.

PMID- 16407053
TI  - Re: Time to development of symptomatic urinary calculi in a high risk
      environment.

PMID- 16407054
TI  - Re: Clitoral anatomy in nulliparous, healthy, premenopausal volunteers using
      unenhanced magnetic resonance imaging.

PMID- 16407056
TI  - Re: How little is enough? The evidence for post-vasectomy testing.

PMID- 16407058
TI  - Electron-induced enzyme activation.

PMID- 16407059
TI  - The double life of aconitase.

PMID- 16407060
TI  - Topological determinants of protein domain swapping.
AB  - Protein domain swapping has been repeatedly observed in a variety of proteins and
      is believed to result from destabilization due to mutations or changes in
      environment. Based on results from our studies and others, we propose that
      structures of the domain-swapped proteins are mainly determined by their native
      topologies. We performed molecular dynamics simulations of seven different
      proteins, known to undergo domain swapping experimentally, under mildly
      denaturing conditions and found in all cases that the domain-swapped structures
      can be recapitulated by using protein topology in a simple protein model. Our
      studies further indicated that, in many cases, domain swapping occurs at
      positions around which the protein tends to unfold prior to complete unfolding.
      This, in turn, enabled prediction of protein structural elements that are
      responsible for domain swapping. In particular, two distinct domain-swapped dimer
      conformations of the focal adhesion targeting domain of focal adhesion kinase
      were predicted computationally and were supported experimentally by data obtained
      from NMR analyses.

PMID- 16407061
TI  - The mechanism of HIV-1 core assembly: insights from three-dimensional
      reconstructions of authentic virions.
AB  - Infectious HIV particles contain a characteristic cone-shaped core encasing the
      viral RNA and replication proteins. The core exhibits significant heterogeneity
      in size and shape, yet consistently forms a well-defined structure. The mechanism
      by which the core is assembled in the maturing virion remains poorly understood.
      Using cryo-electron tomography, we have produced three-dimensional
      reconstructions of authentic, unstained HIV-1. These reveal the viral morphology
      with unprecedented clarity and suggest the following mechanism for core formation
      inside the extracellular virion: core growth initiates at the narrow end of the
      cone and proceeds toward the distal side of the virion until limited by the viral
      membrane. Curvature and closure of the broad end of the core are then directed by
      the inner surface of the viral membrane. This mechanism accommodates significant
      flexibility in lattice growth while ensuring the closure of cores of variable
      size and shape.

PMID- 16407062
TI  - The structure of the N-terminal domain of the fragile X mental retardation
      protein: a platform for protein-protein interaction.
AB  - FMRP, whose lack of expression causes the X-linked fragile X syndrome, is a
      modular RNA binding protein thought to be involved in posttranslational
      regulation. We have solved the structure in solution of the N-terminal domain of
      FMRP (NDF), a functionally important region involved in multiple interactions.
      The structure consists of a composite fold comprising two repeats of a Tudor
      motif followed by a short alpha helix. The interactions between the three
      structural elements are essential for the stability of the NDF fold. Although
      structurally similar, the two repeats have different dynamic and functional
      properties. The second, more flexible repeat is responsible for interacting both
      with methylated lysine and with 82-FIP, one of the FMRP nuclear partners. NDF
      contains a 3D nucleolar localization signal, since destabilization of its fold
      leads to altered nucleolar localization of FMRP. We suggest that the NDF
      composite fold determines an allosteric mechanism that regulates the FMRP
      functions.

PMID- 16407064
TI  - Dual requirement for flexibility and specificity for binding of the coiled-coil
      tropomyosin to its target, actin.
AB  - The coiled coil is a widespread motif involved in oligomerization and protein
      protein interactions, but the structural requirements for binding to target
      proteins are poorly understood. To address this question, we measured binding of
      tropomyosin, the prototype coiled coil, to actin as a model system. Tropomyosin
      binds to the actin filament and cooperatively regulates its function. Our results
      support the hypothesis that coiled-coil domains that bind to other proteins are
      flexible. We made mutations that alter interface packing and stability as well as
      mutations in surface residues in a postulated actin binding site. Actin affinity,
      measured by cosedimentation, was correlated with coiled-coil stability and local
      instability and side chain flexibility, analyzed with circular dichroism and
      fluorescence spectroscopy. The flexibility from interruptions in the stable
      coiled-coil interface is essential for actin binding. The surface residues in a
      postulated actin binding site participate in actin binding when the coiled coil
      within it is poorly packed.

PMID- 16407063
TI  - The structures of the thrombospondin-1 N-terminal domain and its complex with a
      synthetic pentameric heparin.
AB  - The N-terminal domain of thrombospondin-1 (TSPN-1) mediates the protein's
      interaction with (1) glycosaminoglycans, calreticulin, and integrins during
      cellular adhesion, (2) low-density lipoprotein receptor-related protein during
      uptake and clearance, and (3) fibrinogen during platelet aggregation. The crystal
      structure of TSPN-1 to 1.8 A resolution is a beta sandwich with 13 antiparallel
      beta strands and 1 irregular strand-like segment. Unique structural features of
      the N- and C-terminal regions, and the disulfide bond location, distinguish TSPN
      1 from the laminin G domain and other concanavalin A-like lectins/glucanases
      superfamily members. The crystal structure of the complex of TSPN-1 with heparin
      indicates that residues R29, R42, and R77 in an extensive positively charged
      patch at the bottom of the domain specifically associate with the sulfate groups
      of heparin. The TSPN-1 structure and identified adjacent linker region provide a
      structural framework for the analysis of the TSPN domain of various molecules,
      including TSPs, NELLs, many collagens, TSPEAR, and kielin.

PMID- 16407065
TI  - A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a
      mechanism of electron transfer by diflavin reductases.
AB  - NADPH-cytochrome P450 reductase transfers two reducing equivalents derived from a
      hydride ion of NADPH via FAD and FMN to the large family of microsomal cytochrome
      P450 monooxygenases in one-electron transfer steps. The mechanism of electron
      transfer by diflavin reductases remains elusive and controversial. Here, we
      determined the crystal structure of truncated yeast NADPH-cytochrome P450
      reductase, which is functionally active toward its physiological substrate
      cytochrome P450, and discovered a second FMN binding site at the interface of the
      connecting and FMN binding domains. The two FMN binding sites have different
      accessibilities to the bulk solvent and different amino acid environments,
      suggesting stabilization of different electronic structures of the reduced
      flavin. Since only one FMN cofactor is required for function, a hypothetical
      mechanism of electron transfer is discussed that proposes shuttling of a single
      FMN between these two sites coupled with the transition between two semiquinone
      forms, neutral (blue) and anionic (red).

PMID- 16407067
TI  - Structure and interactions at the viral surface of the envelope protein E1 of
      Semliki Forest virus.
AB  - Semliki Forest virus (SFV) is enveloped by a lipid bilayer enclosed within a
      glycoprotein cage made by glycoproteins E1 and E2. E1 is responsible for inducing
      membrane fusion, triggered by exposure to the acidic environment of the
      endosomes. Acidic pH induces E1/E2 dissociation, allowing E1 to interact with the
      target membrane, and, at the same time, to rearrange into E1 homotrimers that
      drive the membrane fusion reaction. We previously reported a preliminary Calpha
      trace of the monomeric E1 glycoprotein ectodomain and its organization on the
      virus particle. We also reported the 3.3 A structure of the trimeric, fusogenic
      conformation of E1. Here, we report the crystal structure of monomeric E1 refined
      to 3 A resolution and describe the amino acids involved in contacts in the
      virion. These results identify the major determinants for the E1/E2 icosahedral
      shell formation and open the way to rational mutagenesis approaches to shed light
      on SFV assembly.

PMID- 16407066
TI  - Mapping the structure and function of the E1 and E2 glycoproteins in
      alphaviruses.
AB  - The 9 A resolution cryo-electron microscopy map of Sindbis virus presented here
      provides structural information on the polypeptide topology of the E2 protein, on
      the interactions between the E1 and E2 glycoproteins in the formation of a
      heterodimer, on the difference in conformation of the two types of trimeric
      spikes, on the interaction between the transmembrane helices of the E1 and E2
      proteins, and on the conformational changes that occur when fusing with a host
      cell. The positions of various markers on the E2 protein established the
      approximate topology of the E2 structure. The largest conformational differences
      between the icosahedral surface spikes at icosahedral 3-fold and quasi-3-fold
      positions are associated with the monomers closest to the 5-fold axes. The long
      E2 monomers, containing the cell receptor recognition motif at their extremities,
      are shown to rotate by about 180 degrees and to move away from the center of the
      spikes during fusion.

PMID- 16407068
TI  - The crystal structure of murine coronin-1: a regulator of actin cytoskeletal
      dynamics in lymphocytes.
AB  - Mammalian coronin-1 is preferentially expressed in hematopoietic cells and plays
      a poorly understood role in the dynamic reorganization of the actin cytoskeleton.
      Sequence analysis of coronin-1 revealed five WD40 repeats that were predicted to
      form a beta propeller. They are followed by a 130 residue extension and a 30
      residue leucine zipper domain that is responsible for multimerization of the
      protein. Here, we present the crystal structure of murine coronin-1 without the
      leucine zipper at 1.75 A resolution. Coronin-1 forms a seven-bladed beta
      propeller composed of the five predicted WD40 repeats and two additional blades
      that lack any homology to the canonical WD40 motif. The C-terminal extension
      adopts an extended conformation, packs tightly against the bottom surface of the
      propeller, and is likely to be required for the structural stability of the
      propeller. Analysis of charged and conserved surface residues delineate possible
      binding sites for F-actin on the beta propeller.

PMID- 16407069
TI  - Structural interpretation of hydrogen exchange protection factors in proteins:
      characterization of the native state fluctuations of CI2.
AB  - Protection factors obtained from equilibrium hydrogen exchange experiments are an
      important source of structural information on both native and nonnative states of
      proteins. We present a method for determining ensembles of protein structures by
      using hydrogen exchange data as restraints in molecular dynamics simulations in
      conjunction with an empirical force-field. The method is applied to determine the
      ensemble of structures representing the native state of chymotrypsin inhibitor 2
      (CI2), including the rare, large fluctuations responsible for hydrogen exchange.

PMID- 16407070
TI  - Activation and catalysis of the di-heme cytochrome c peroxidase from Paracoccus
      pantotrophus.
AB  - Bacterial cytochrome c peroxidases contain an electron transferring (E) heme
      domain and a peroxidatic (P) heme domain. All but one of these enzymes are
      isolated in an inactive oxidized state and require reduction of the E heme by a
      small redox donor protein in order to activate the P heme. Here we present the
      structures of the inactive oxidized and active mixed valence enzyme from
      Paracoccus pantotrophus. Chain flexibility in the former, as expressed by the
      crystallographic temperature factors, is strikingly distributed in certain loop
      regions, and these coincide with the regions of conformational change that occur
      in forming the active mixed valence enzyme. On the basis of these changes, we
      postulate a series of events that occur to link the trigger of the electron
      entering the E heme from either pseudoazurin or cytochrome c(550) and the
      dissociation of a coordinating histidine at the P heme, which allows substrate
      access.

PMID- 16407071
TI  - Structural switch of the gamma subunit in an archaeal aIF2 alpha gamma
      heterodimer.
AB  - Eukaryotic and archaeal initiation factors 2 (e/aIF2) are heterotrimeric proteins
      (alphabetagamma) supplying the small subunit of the ribosome with methionylated
      initiator tRNA. This study reports the crystallographic structure of an
      aIF2alphagamma heterodimer from Sulfolobus solfataricus bound to Gpp(NH)p-Mg(2+).
      aIF2gamma is in a closed conformation with the G domain packed on domains II and
      III. The C-terminal domain of aIF2alpha interacts with domain II of aIF2gamma.
      Conformations of the two switch regions involved in GTP binding are similar to
      those encountered in an EF1A:GTP:Phe-tRNA(Phe) complex. Comparison with the EF1A
      structure suggests that only the gamma subunit of the aIF2alphagamma heterodimer
      contacts tRNA. Because the alpha subunit markedly reinforces the affinity of tRNA
      for the gamma subunit, a contribution of the alpha subunit to the switch
      movements observed in the gamma structure is considered.

PMID- 16407072
TI  - Crystal structure of human iron regulatory protein 1 as cytosolic aconitase.
AB  - Iron regulatory proteins (IRPs) control the translation of proteins involved in
      iron uptake, storage and utilization by binding to specific noncoding sequences
      of the corresponding mRNAs known as iron-responsive elements (IREs). This strong
      interaction assures proper iron homeostasis in animal cells under iron shortage.
      Conversely, under iron-replete conditions, IRP1 binds a [4Fe-4S] cluster and
      functions as cytosolic aconitase. Regulation of the balance between the two IRP1
      activities is complex, and it does not depend only on iron availability. Here, we
      report the crystal structure of human IRP1 in its aconitase form. Comparison with
      known structures of homologous enzymes reveals well-conserved folds and active
      site environments with significantly different surface shapes and charge
      distributions. The specific features of human IRP1 allow us to propose a
      tentative model of an IRP1-IRE complex that agrees with a range of previously
      obtained data.

PMID- 16407073
TI  - Dynamic binding of PKA regulatory subunit RI alpha.
AB  - Recent crystal structures have revealed that regulatory subunit RIalpha of PKA
      undergoes a dramatic conformational change upon complex formation with the
      catalytic subunit. Molecular dynamics studies were initiated to elucidate the
      contributions of intrinsic conformational flexibility and interactions with the
      catalytic subunit in formation and stabilization of the complex. Simulations of a
      single RIalpha nucleotide binding domain (NBD), missing cAMP, showed that its C
      helix spontaneously occupies two distinct conformations: either packed against
      the nucleotide binding domain as in its cAMP bound structure, or extended into an
      intermediate form resembling that of the holoenzyme structure. C helix extension
      was not seen in a simulation of either RIalpha NBD. In a model complex containing
      both NBDs and the catalytic subunit, well-conserved residues at the interface
      between the NBDs in the cAMP bound form were found to stabilize the complex
      through contacts with the catalytic subunit. The model structure is consistent
      with available experimental data.

PMID- 16407074
TI  - Multipurpose MRG domain involved in cell senescence and proliferation exhibits
      structural homology to a DNA-interacting domain.
AB  - The ubiquitous MRG/MORF family of proteins is involved in cell senescence, or the
      terminal loss of proliferative potential, a model for aging and tumor suppression
      at the cellular level. These proteins are defined by the approximately 20 kDa MRG
      domain that binds a plethora of transcriptional regulators and chromatin
      remodeling factors, including the histone deacetylase transcriptional corepressor
      mSin3A and the novel nuclear protein PAM14, and they are also known components of
      the Tip60/NuA4 complex via interactions with the MRG binding protein (MRGBP). We
      present here the crystal structure of a prototypic MRG domain from human MRG15
      whose core consists of two orthogonal helix hairpins. Despite the lack of
      sequence similarity, the core structure has surprisingly striking homology to a
      DNA-interacting domain of the tyrosine site-specific recombinases XerD, lambda
      integrase, and Cre. Site-directed mutagenesis studies based on the X-ray
      structure and bioinformatics identified key residues involved in the binding of
      PAM14 and MRGBP.

PMID- 16407075
TI  - Structure of the forkhead domain of FOXP2 bound to DNA.
AB  - FOXP (FOXP1-4) is a newly defined subfamily of the forkhead box (FOX)
      transcription factors. A mutation in the FOXP2 forkhead domain cosegregates with
      a severe speech disorder, whereas several mutations in the FOXP3 forkhead domain
      are linked to the IPEX syndrome in human and a similar autoimmune phenotype in
      mice. Here we report a 1.9 A crystal structure of the forkhead domain of human
      FOXP2 bound to DNA. This structure allows us to revise the previously proposed
      DNA recognition mechanism and provide a unifying model of DNA binding for the FOX
      family of proteins. Our studies also reveal that the FOXP2 forkhead domain can
      form a domain-swapped dimer, made possible by a strategic substitution of a
      highly conserved proline in conventional FOX proteins with alanine in the P
      subfamily. Disease-causing mutations in FOXP2 and FOXP3 map either to the DNA
      binding surface or the domain-swapping dimer interface, functionally
      corroborating the crystal structure.

PMID- 16407077
TI  - Comparative renal anatomy of exotic species.
AB  - All living organisms consume nutrients that are required for the production of
      both tissue and energy. The waste products of this process include nitrogenous
      materials and inorganic salts. They are removed from the body by excretory
      organs, which in vertebrate shave developed into kidneys and into salt glands in
      some birds and reptiles. Many invertebrates use a series of excretory organs
      called nephridia to perform the same function. Even though they perform similar
      functions, there is no evolutionary connection between invertebrate nephridia and
      vertebrate kidneys. Both evolved independently.

PMID- 16407078
TI  - Comparative renal physiology of exotic species.
AB  - In this article the osmoregulatory, acid-base homeostasis, and excretory
      functions of the renal system of invertebrates and vertebrates are reviewed. The
      mammalian renal system is the most highly evolved in terms of the range of
      functions performed by the kidneys. Renal physiology in other animals can be very
      different, and a sound knowledge of these differences is important for
      understanding health and disease processes that involve the kidneys, as well as
      ion and water homeostasis. Many animals rely on multiple organs along with the
      kidneys to maintain osmotic, ionic, and pH balance. Some animals rely heavily on
      postrenal modification of urine to conserve water and salt balance; this can
      influence the interpretation of disease signs and treatment modalities.

PMID- 16407079
TI  - Exotic mammal renal disease: causes and clinical presentation.
AB  - Renal disease is not uncommon in exotic mammals, with degenerative,infectious
      (bacterial, viral, parasitic), metabolic, nutritional,neoplastic, anatomic, and
      toxic causes all represented. This article discusses the clinical presentation
      for the various renal diseases affecting exotic mammals. Anatomic pathology at
      the gross and microscopic level is reviewed, as is disease pathophysiology unique
      to the species under discussion.

PMID- 16407081
TI  - Types of renal disease in avian species.
AB  - Renal disease in birds is frequently encountered. Like most other animals, birds
      are susceptible to a full spectrum of renal insults,such as toxins, tumors,
      infections, and degenerative conditions. Accurate diagnosis of renal disease is
      based on a complete history,physical examination, and laboratory evaluation of
      the patient. Because it is often required for a more definitive diagnosis,
      special attention is given to histopathologic evaluation of renal tissue,whether
      through a premortem biopsy or collection at gross necropsy.

PMID- 16407080
TI  - Exotic mammal renal disease: diagnosis and treatment.
AB  - Knowledge of the renal anatomy and clinical pathology associated with renal
      disease can help the practitioner with interpretation of imaging procedures and
      urine, blood, and serum biochemical values. This article discusses specimen
      collection techniques, along with species variables in several clinical pathology
      parameters. Diagnostic tools and interpretations are discussed for the more
      common renal maladies affecting exotic mammals. Treatment guidelines are offered
      for general as well as specific exotic mammal renal diseases.

PMID- 16407082
TI  - Diagnosis and treatment of avian renal disease.
AB  - Reports on the incidence of renal disease in the avian patient vary,but renal
      disease is common in poultry and birds of prey. Clinical renal disease is
      probably under-recognized in the companion bird,with the notable exception of
      renal tumors in the budgerigar (Melopsittacusundulatus). Diagnosis of renal
      disease may rely on the identification of consistent clinical signs, clinical
      pathology, survey radiographs, and laparoscopic evaluation and biopsy of the
      kidneys. Treatment of avian renal disease relies on supportive care such as fluid
      therapy and nutritional support. Other treatments vary with the underlying cause
      and the clinical picture but may include systemic antibiotics, diuretics,
      parenteral vitamin A, and agents to lower uric acid levels such as allopurinol.

PMID- 16407083
TI  - Renal pathology in reptiles.
AB  - The class of Reptilia varies widely. Both the gross morphology and microscopic
      anatomy of the kidneys are specific for each species. In each species of reptile,
      the physiology of the renal system has adapted to the specific conditions of
      life, including, among other factors, the type of food, environmental
      temperature, and the availability of water. The pathology of the kidneys in
      reptiles has been poorly studied, but in recent years a number of investigators
      have specifically studied reptilian renal pathology.

PMID- 16407084
TI  - Renal diseases of reptiles.
AB  - Renal disease is one of the most common problems in reptilian medicine.
      Herbivorous species seem to be more susceptible than carnivores. The causation
      may be multifactorial, and the signs are often nonspecific. Prevention is
      preferred to treatment, and a comprehensive health program, which includes
      quarantine, routine health screens during annual examinations, and necropsy
      examinations of all animals that die, is desirable.

PMID- 16407085
TI  - Amphibian renal disease.
AB  - Amphibians by nature have an intimate connection with the aquatic environment at
      some stage of development and fight an osmotic battle due to the influx of water.
      Many amphibians have acquired a more terrestrial existence at later stages of
      development and consequently have physiologic adaptations to conserve moisture.
      Renal adaptations have allowed amphibians successfully to bridge the gap between
      aqueous and terrestrial habitats. The kidneys, skin,and, in many amphibian
      species, the urinary bladder play key roles in fluid homeostasis. Renal
      impairment may be responsible for the clinical manifestation of disease,
      morbidity, and mortality.

PMID- 16407086
TI  - Patterns of exposures at school among children age 6-19 years reported to Texas
      poison centers, 1998-2002.
AB  - Although children and adolescents spend a large amount of time in school, there
      is little information on the factors involved in school exposures that are
      reported to poison centers. This study used data involving exposures among
      children age 6-19 yr reported to 6 Texas poison centers during 1998-2002. The
      distribution of school and nonschool exposures was determined for various
      demographic and other factors, and comparisons were made between the two types of
      exposures. The lowest proportion of reported school exposures occurred in June
      August and the next lowest proportion occurred in December-January; nonschool
      exposures were more constant throughout the year. Males accounted for 58% of
      school exposures and 49% of nonschool exposures. The exposure was unintentional
      in 74% of school and 67% of nonschool exposures. Ingestion was the most
      frequently reported exposure route for school (64%) and nonschool (76%)
      exposures. Among those cases with known medical outcome, the most frequently
      reported medical outcome involved minor effects for both school exposures (58%)
      and nonschool exposures (46%). Nonpharmaceuticals were involved in 75% of school
      exposures and 48% of nonschool exposures. The most frequently reported substances
      involved in school exposures were arts, crafts, and office supplies (18%), while
      the most frequently reported substances involved in nonschool exposures were
      analgesics (17%). This information may allow school administrators and health
      care providers to implement prevention strategies.

PMID- 16407087
TI  - Interactive effects between CYP1A1 genotypes and environmental polychlorinated
      dibenzo-p-dioxins and dibenzofurans exposures on liver function profile.
AB  - Previous studies reported that polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) induced hepatic cytochrome P-4501A1 (CYP1A1). The aim of
      this study was to examine the interactive influence of CYP1A1 genotypes and
      PCDD/Fs exposure on liver function profile. PCDD/Fs levels and liver function
      parameters were determined in serum and correlated with genetic polymorphism of
      CYP1A1/Msp 1 in 225 human volunteers who had no or minimal occupational exposure
      to PCDD/F. The results showed that the highest glutamate pyruvate transaminase
      (GPT) activity levels were found in subjects with homozygous variant CYP1A1/Msp
      1, followed by heterozygous variant, and finally homozygous wild type for those
      individuals whose serum PCDD/Fs levels were higher than 17.4 pg WHO-TEQ/g lipid.
      Data suggest that GPT activity levels may be modified by interaction of
      CYP1A1/Msp 1 genotype with dioxin after adjustment for age, alcohol consumption,
      and history of liver illness. Further studies are needed to characterize the
      variation in other related genes to verify whether a correlation exists between
      serum PCDD/Fs levels and adverse health effects.

PMID- 16407088
TI  - Immunomodulatory effects of in vitro exposure to organochlorines on T-cell
      proliferation in marine mammals and mice.
AB  - Marine mammals bioaccumulate various environmental contaminants such as
      organochlorines (OCs), which biomagnify via the food web. While the
      immunomodulatory effects of individual OCs have been studied, the effects of
      mixtures are not well understood. The immunomodulatory effects of polychlorinated
      biphenyl (PCB) 138, 153, 169, and 180 as well as 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) and all possible mixtures were examined in marine mammals and mice.
      Lymphocyte proliferation was significantly modulated by OCs in all species
      tested, mostly by non-coplanar PCBs, as shown using regression analyses.
      Correlation analyses showed significant correlations (interpreted as additive
      effects) between OCs in mice, killer whales, and Steller sea lions. Nonadditive
      synergistic and antagonistic interactions between OCs were detected in most of
      the species tested. Toxic equivalency (TEQ) values used for OC toxicity
      assessment failed to predict the immunomodulatory effects measured in mice and
      marine mammals. The commonly used mouse model failed to predict immunomodulatory
      effects in other species. Clustering data suggested that phylogeny does not
      predict toxicity of OCs. Overall, our data suggest the presence of species
      specific sensitivities to different mixtures, in which OCs interactions may be
      complex and that may exert their effects through dioxinlike or dioxin-independent
      pathways. Lastly, lymphocyte proliferation, an important part of adaptive
      immunity, was significantly modulated in mice and marine mammals, suggesting the
      possibility of increased susceptibility to diseases. These findings will be
      useful to better characterize the risk associated with OC exposure and possibly
      lead to new conservation and management strategies.

PMID- 16407089
TI  - Elimination of the cyanobacterial hepatotoxin microcystin from the freshwater
      pulmonate snail Lymnaea stagnalis jugularis (say).
AB  - It has been suggested that little to no microcystin (MC), a cyanobacterial
      hepatotoxin, accumulates within freshwater pulmonate snails because the toxin is
      associated primarily with undigested gut contents that are eliminated from the
      animal via egestion. To test this, Lymnaea stagnalis exposed to MC-containing
      cyanobacteria were placed into toxin-free environments and sampled over short (24
      h at 21 degrees C) and long (30 d at 22 and 10 degrees C) time periods. Within 8
      h after being removed from exposure to microcystin-containing phytoplankton, the
      gizzard and cecal string fractions of the feces were eliminated, accounting for
      57% of the initial MC concentration. However, detectable concentrations remained
      beyond 24 h, likely in association with the digestive-gland contents, which can
      be retained up to 100 h. Long-term MC loss was biphasic at two ambient
      temperatures. The greatest change (fast phase) occurred over the first 3 d after
      exposure. By 6 d, the cumulative MC loss from L. stagnalis was 80 and 95% at 10
      and 22 degrees C, respectively. Toxin loss over this period was attributed to
      egestion of indigestible cells/colonies from gizzard and cecum, as well as
      elimination of unassimilated MC-laden fragments and vacuolate excretion of
      residues from the digestive gland. The fast-phase depuration rate constant was
      significantly higher at 22 than at 10 degrees C, indicating an influence of
      ambient temperature on the rate of toxin loss from pulmonate snails. Depuration
      continued at slower rates until 30 d, when most (97.5 and 99.5% at 10 and 22
      degrees C, respectively) of the initial MC was eliminated.

PMID- 16407090
TI  - Estimates of exposures to perchlorate from consumption of human milk, dairy milk,
      and water, and comparison to current reference dose.
AB  - To develop an enforceable drinking water standard from a health-based reference
      dose, sources of exposure and relevant exposure factors across the U.S.
      population must be considered. Human exposures, expressed as an estimated daily
      exposure, can be used to evaluate the health protectiveness of a range of
      potential regulatory values, thus providing a scientific foundation on which
      decisions can be based. Recent evidence points to detectable levels of
      perchlorate in milk and other foods. The purpose of this article is to estimate
      human exposure to perchlorate from ingestion of drinking water, human milk, and
      dairy milk. Drinking-water exposure was based on a range of possible regulatory
      values, derived from the recently established reference dose. Exposure to
      perchlorate from the consumption of milk was based on exploratory Food and Drug
      Administration dairy milk data, and on additional published perchlorate
      concentrations in dairy and human milk samples. This effort is exploratory in
      nature due to the limited data available at this time. However, it is anticipated
      that these exposure estimates and comparison with the current reference dose will
      stimulate dialogue and research that will advance the risk assessment for
      perchlorate.

PMID- 16407091
TI  - Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada
      geese (Branta canadensis).
AB  - A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash
      pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity
      of V toxicity data for wild birds, a series of studies was undertaken using the
      forms of V believed to have resulted in this incident. In 7-d single oral dose
      trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose
      (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for
      sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more
      potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive
      histopathological lesion of both forms of V was lympho-granulocytic enteritis
      with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and
      kidney was proportional to the administered dose, and predictive analyses based
      on these data suggest that V concentrations of 10 microg/g dry weight (dw) in
      liver and 25 microg/g dw in kidney are associated with mortality (>90% confidence
      that exposure is >LD50) in mallards acutely exposed to sodium metavanadate.
      Chronic exposure to increasing dietary concentrations of sodium metavanadate
      (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2
      and 13.6 microg/g dw, respectively), mild intestinal hemorrhage, blood chemistry
      changes, and evidence of hepatic oxidative stress in mallards, although some of
      these responses may have been confounded by food avoidance and weight loss.
      Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in
      modest accumulation of V in liver and kidney (<5 microg/g dw) and mild intestinal
      hemorrhage. Based on these data and other observations, it is unlikely that
      chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife.
      However, point sources, such as the V-laden fly ash pond encountered by geese at
      the petroleum refinery in Delaware, may pose a significant hazard to water birds.

PMID- 16407092
TI  - Disposition of BDE 47 in developing mice.
AB  - Despite its minor contribution to global polybrominated diphenyl ether (PBDE)
      production and usage, 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) is the dominant
      congener found in most biotic samples in North America. The majority of public
      health concern has focused on potential hazardous effects resulting from exposure
      of infants and young children to BDE 47 because of previous studies reporting
      adverse developmental effects in rodent studies, in combination with human
      exposure estimates suggesting that nursing infants and young children have the
      highest exposure to BDE 47. This study was designed with two objectives: (1) to
      investigate the disposition of BDE 47 in infantile mice reported to be
      susceptible to BDE 47 and (2) to investigate the disposition and excretion of BDE
      47 at various developmental stages in an attempt to further identify the
      mechanism responsible for rapid urinary excretion. The disposition of (14)C-BDE
      47 was monitored in C57BL/6 mice following a single oral dose of BDE 47 (1 mg/kg)
      at different stages of development. The results show that the toxicokinetics of
      BDE 47 are different in developing mice than in adult mice; whereas disposition
      patterns are similar, concentrations of BDE 47 are higher in pups because they
      have a reduced capacity to excrete BDE 47. These differences lead to higher
      concentrations of BDE 47 at target tissues during critical windows of
      development.

PMID- 16407093
TI  - Hypersensitivity of prediabetic JCR:LA-cp rats to fine airborne combustion
      particle-induced direct and noradrenergic-mediated vascular contraction.
AB  - Particulate matter with mean aerodynamic diameter < or =2.5 microm (PM(2.5)),
      from diesel exhaust, coal or residual oil burning, and from industrial plants, is
      a significant component of airborne pollution. Type 2 diabetes is associated with
      enhanced risk of adverse cardiovascular events following exposure to PM(2.5).
      Particle properties, sources, and pathophysiological mechanisms responsible are
      unknown. We studied effects of residual oil fly ash (ROFA) from a large U.S.
      powerplant on vascular function in a prediabetic, hyperinsulinemic model, the
      JCR:LA-cp rat. Residual oil fly ash leachate (ROFA-L) was studied using aortic
      rings from young-adult, obese, insulin-resistant rats and lean normal rats in
      vitro. Contractile response to phenylephrine and relaxant response to
      acetylcholine were determined in the presence and absence of L-NAME (N(G)-nitro-L
      arginine methyl ester). In a separate series of studies, the direct contractile
      effects of ROFA-L on repeated exposure were determined. ROFA-L (12.5 microg ml(
      1)) increased phenylephrine-mediated contraction in obese (p < 0.05), but not in
      lean rat aortae, with the effect being exacerbated by L-NAME, and it reduced
      acetylcholine-mediated relaxation of both obese and lean aortae (p < 0.0001).
      Initial exposure of aortae to ROFA-L caused a small contractile response (<0.05
      g), which was markedly greater on second exposure in the obese (approximately 0.6
      g, p < 0.0001) aortae but marginal in lean (approximately 0.1 g) aortae. Our data
      demonstrate that bioavailable constituents of oil combustion particles enhance
      noradrenergic-mediated vascular contraction, impair endothelium-mediated
      relaxation, and induce direct vasocontraction in prediabetic rats. These
      observations provide the first direct evidence of the causal properties of
      PM(2.5) and identify the pathophysiological role of the early prediabetic state
      in susceptibility to environmentally induced cardiovascular disease. These are
      important implications for public health and public policy.

PMID- 16407094
TI  - Research strategies for safety evaluation of nanomaterials. Part VI.
      Characterization of nanoscale particles for toxicological evaluation.
AB  - To properly assign mechanisms or causes for toxic effects of nanoscale materials,
      their properties and characteristics both outside and within the biological
      environment must be well understood. Scientists have many tools for studying the
      size, shape, and surface properties of particulates outside of the physiological
      environment; however, it is difficult to measure many of these same properties in
      situ without perturbing the environment, leading to spurious findings.
      Characterizing nanoparticle systems in situ can be further complicated by an
      organism's active clearance, defense, and/or immune responses. As toxicologists
      begin to examine nanomaterials in a systematic fashion, there is consensus that a
      series of guidelines or recommended practices is necessary for basic
      characterization of nanomaterials. These recommended practices should be
      developed jointly by physical scientists skilled in nano characterization and
      biological scientists experienced in toxicology research. In this article, basic
      nanoparticle characterization techniques are discussed, along with the some of
      the issues and implications associated with measuring nanoparticle properties and
      their interactions with biological systems. Recommendations regarding how best to
      approach nanomaterial characterization include using proper sampling and
      measurement techniques, forming multidisciplinary teams, and making measurements
      as close to the biological action point as possible.

PMID- 16407095
TI  - Correction of the sickle cell mutation in embryonic stem cells.
AB  - Sickle cell anemia is one of the most common genetic diseases worldwide. Patients
      often suffer from anemia, painful crises, infections, strokes, and
      cardiopulmonary complications. Although current management has improved the
      quality of life and survival of patients, cure can be achieved only with bone
      marrow transplantation when histocompatible donors are available. The ES cell
      technology suggests that a therapeutic cloning approach may be feasible for
      treatment of this disease. Using a transgenic/knockout sickle cell anemia mouse
      model, which harbors 240 kb of human DNA sequences containing the beta(S)-globin
      gene, we prepared ES cells from blastocysts that had the sickle cells anemia
      genotype and carried out homologous recombination with DNA constructs that
      contained the beta(A)-globin gene. We obtained ES cells in which the beta(S) was
      corrected to the beta(A) sequence. Hematopoietic cells differentiated from these
      ES cells produced both hemoglobin A and hemoglobin S. This approach can be
      applied to human ES cells to correct the sickle mutation as well as beta
      thalassemia mutations.

PMID- 16407096
TI  - Herbicide-binding sites revealed in the structure of plant acetohydroxyacid
      synthase.
AB  - The sulfonylureas and imidazolinones are potent commercial herbicide families.
      They are among the most popular choices for farmers worldwide, because they are
      nontoxic to animals and highly selective. These herbicides inhibit branched-chain
      amino acid biosynthesis in plants by targeting acetohydroxyacid synthase (AHAS,
      EC 2.2.1.6). This report describes the 3D structure of Arabidopsis thaliana AHAS
      in complex with five sulfonylureas (to 2.5 A resolution) and with the
      imidazolinone, imazaquin (IQ; 2.8 A). Neither class of molecule has a structure
      that mimics the substrates for the enzyme, but both inhibit by blocking a channel
      through which access to the active site is gained. The sulfonylureas approach
      within 5 A of the catalytic center, which is the C2 atom of the cofactor thiamin
      diphosphate, whereas IQ is at least 7 A from this atom. Ten of the amino acid
      residues that bind the sulfonylureas also bind IQ. Six additional residues
      interact only with the sulfonylureas, whereas there are two residues that bind IQ
      but not the sulfonylureas. Thus, the two classes of inhibitor occupy partially
      overlapping sites but adopt different modes of binding. The increasing emergence
      of resistant weeds due to the appearance of mutations that interfere with the
      inhibition of AHAS is now a worldwide problem. The structures described here
      provide a rational molecular basis for understanding these mutations, thus
      allowing more sophisticated AHAS inhibitors to be developed. There is no
      previously described structure for any plant protein in complex with a commercial
      herbicide.

PMID- 16407097
TI  - Ras pathway signaling accelerates programmed cell death in the pathogenic fungus
      Candida albicans.
AB  - A better understanding of the molecular basis of programmed cell death (PCD) in
      fungi could provide information that is useful in the design of antifungal drugs
      that combat life-threatening fungal infections. Harsh environmental stresses,
      such as acetic acid or hydrogen peroxide, have been shown to induce PCD in the
      pathogenic fungus Candida albicans. In this study, we show that dying cells
      progress from an apoptotic state to a secondary necrotic state and that the rate
      at which this change occurs is proportional to the intensity of the stimulus.
      Also, we found that the temporal response is modulated by Ras-cAMP-PKA signals.
      Mutations that block Ras-cAMP-PKA signaling (ras1Delta, cdc35Delta, tpk1Delta,
      and tpk2Delta) suppress or delay the apoptotic response, whereas mutations that
      stimulate signaling (RAS1(val13) and pde2Delta) accelerate the rate of entry of
      cells into apoptosis. Pharmacological stimulation or inhibition of Ras signaling
      reinforces these findings. Transient increases in endogenous cAMP occur under
      conditions that stimulate apoptosis but not growth arrest. Death-specific changes
      in the abundance of different isoforms of the PKA regulatory subunit, Bcy1p, are
      also observed. Activation of Ras signals may regulate PCD of C. albicans, either
      by inhibiting antiapoptotic functions (such as stress responses) or by activating
      proapoptotic functions.

PMID- 16407098
TI  - Cryptic species within the cosmopolitan desiccation-tolerant moss Grimmia
      laevigata.
AB  - The common cushion moss Grimmia laevigata (Bridel) Bridel grows on bare rock in a
      broad range of environments on every continent except Antarctica. As such, it
      must harbor adaptations to a remarkably broad set of environmental stresses, the
      extremes of which can include very high temperatures, prolonged nearly complete
      desiccation, and high ultraviolet B (UVB) exposure. Yet, like many mosses, G.
      laevigata shows very little morphological variability across its cosmopolitan
      range. This presents an evolutionary puzzle, the solution to which lies in
      understanding the phylogeographic structure of this morphologically simple
      organism. Here we report the results of an analysis of amplified fragment length
      polymorphisms (AFLPs) in G. laevigata, focusing on individuals from the
      California Floristic Province. We found evidence that populations within
      California constitute two distinct geographically overlapping cryptic species.
      Each clade harbors multiple private alleles, indicating they have been
      genetically isolated for some time. We suggest that the existence of cryptic
      species within G. laevigata, in combination with its life history, growth habits,
      and extreme desiccation tolerance, makes this moss an ideal research tool and a
      candidate for a biological indicator of climate change and pollution.

PMID- 16407099
TI  - Germ-line induction of the Caenorhabditis elegans vulva.
AB  - Development of the Caenorhabditis elegans vulva serves as a paradigm for
      intercellular signaling during animal development. In wild-type animals, the
      somatic gonadal anchor cell generates the LIN-3/EGF ligand to induce vulval fates
      in the underlying hypodermis, whereas FBF, FOG-1, and FOG-3 control germ-line
      development. Here we report that FBF functions redundantly with FOG-1 and FOG-3
      to control vulval induction: animals lacking FBF and either FOG-1 or FOG-3 have
      multiple vulvae, the Muv phenotype. The fog; fbf Muv phenotype is generated by
      aberrant induction of vulval precursor cells (VPCs): in wild-type animals, three
      VPCs are induced to form a single vulva, but, in fog; fbf mutants, four or five
      VPCs are typically induced, resulting in ectopic vulvae. Laser ablation
      experiments and mosaic analyses demonstrate that the germ line is critical for
      the fog; fbf Muv phenotype. Consistent with that site of action, we detect FBF
      and FOG-1 in the germ line but not in the VPCs. The simplest interpretation is
      that FOG-1, FOG-3, and FBF act in the germ line to influence vulval fates. The
      LIN-3/EGF ligand may be the germ-line signal to the VPCs: the fog; fbf Muv
      phenotype depends on LIN-3 activity, and the lin-3 3' UTR possesses an FBF
      binding element. Our findings reveal new insights into germ line-to-soma signals
      and the role of PUF proteins in animal development.

PMID- 16407100
TI  - Biochemical basis for dominant mutations in the Saccharomyces cerevisiae MSH6
      gene.
AB  - Here, the ATP-binding, ATP hydrolysis, mispair-binding, sliding clamp formation,
      and Mlh1-Pms1 complex interaction properties of dominant mutant Msh2-Msh6
      complexes have been characterized. The results demonstrate two mechanisms for
      dominance. In one, seen with the Msh6-S1036P and Msh6-G1067D mutant complexes,
      the mutant complex binds mispaired bases, is defective for ATP-induced sliding
      clamp formation and assembly of ternary complexes with Mlh1-Pms1, and occludes
      mispaired bases from other mismatch repair pathways. In the second, seen with the
      Msh6-G1142D complex, the mutant complex binds mispaired bases and is defective
      for ATP-induced sliding clamp formation but assembles ternary complexes with Mlh1
      Pms1 that either occlude the mispaired base or prevent Mlh1-Pms1 from acting in
      alternate mismatch repair pathways.

PMID- 16407101
TI  - Two types of cytotoxic lymphocyte regulation explain kinetics of immune response
      to human immunodeficiency virus.
AB  - The organization of the cytotoxic T lymphocyte (CTL) response at organismal level
      is poorly understood. We propose a mathematical model describing the interaction
      between HIV and its host that explains 20 quantitative observations made in HIV
      infected individuals and simian immunodeficiency virus-infected monkeys,
      including acute infection and response to various antiretroviral therapy
      regimens. The model is built on two modes of CTL activation: direct activation by
      infected cells and indirect activation by CD4 helper cells activated by small
      amounts of virus. Effective infection of helper cells by virus leads to a stable
      chronic infection at high virus load. We assume that CTLs control virus by
      killing infected cells. We explain the lack of correlation between the CTL number
      and the virus decay rate in therapy and predict that individuals with a high
      virus load can be switched to a low-viremia state that will maintain stability
      after therapy, but the switch requires fine adjustment of therapy regimen based
      on the model and individual parameters.

PMID- 16407102
TI  - Revised direct radiocarbon dating of the Vindija G1 Upper Paleolithic
      Neandertals.
AB  - The 1998/1999 direct dating of two Neandertal specimens from level G(1) of
      Vindija Cave in Croatia to approximately 28,000 and approximately 29,000
      radiocarbon ((14)C) years ago has led to interpretations concerning the late
      survival of Neandertals in south-central Europe, patterns of interaction between
      Neandertals and in-dispersing early modern humans in Europe, and complex
      biocultural scenarios for the earlier phases of the Upper Paleolithic. Given
      improvements, particularly in sample pretreatment techniques for bone radiocarbon
      samples, especially ultrafiltration of collagen samples, these Vindija G(1)
      Neandertal fossils are redated to approximately 32,000-33,000 (14)C years ago and
      possibly earlier. These results and the recent redating of a number of
      purportedly old modern human skeletal remains in Europe to younger time periods
      highlight the importance of fine chronological control when studying this
      biocultural time period and the tenuous nature of monolithic scenarios for the
      establishment of modern humans and earlier phases of the Upper Paleolithic in
      Europe.

PMID- 16407103
TI  - Distribution of histone H3.3 in hematopoietic cell lineages.
AB  - We have introduced the histone variant H3.3 into chicken erythroid cell lines and
      examined its distribution in the neighborhood of the folate receptor (FR) and
      beta-globin genes by using high-resolution chromatin immunoprecipitation (ChIP).
      Marked incorporation of tagged H3.3 into the FR gene is confined to its upstream
      regulatory region and is observed whether or not the gene is transcriptionally
      active. Incorporation is also observed over locus control regulatory elements in
      the absence of transcription of genes regulated by these elements, suggesting
      that gene activity per se is not necessarily required to replace H3 with H3.3.
      Other active genes display various behaviors, either incorporating H3.3 over both
      the coding region and upstream regulatory region or over upstream sequences only.
      There is, however, no straightforward correlation between sites of H3.3
      incorporation and regions of enrichment in H3 acetylation and lysine-4
      methylation. In the case of FR and VEGF-D, in which incorporation is confined to
      upstream regions, the presence of exogenous H3 results in reduced expression,
      whereas H3.3 stimulates expression. This finding suggests that these histone
      variants can be active rather than passive participants in regulation of
      expression.

PMID- 16407104
TI  - High-speed microfluidic differential manometer for cellular-scale hydrodynamics.
AB  - We propose a broadly applicable high-speed microfluidic approach for measuring
      dynamical pressure-drop variations along a micrometer-sized channel and
      illustrate the potential of the technique by presenting measurements of the
      additional pressure drop produced at the scale of individual flowing cells. The
      influence of drug-modified mechanical properties of the cell membrane is shown.
      Finally, single hemolysis events during flow are recorded simultaneously with the
      critical pressure drop for the rupture of the membrane. This scale-independent
      measurement approach can be applied to any dynamical process or event that
      changes the hydrodynamic resistance of micro- or nanochannels.

PMID- 16407105
TI  - Immunity and behavior: antibodies alter emotion.
AB  - Systemic lupus erythematosus is an autoimmune disease in which most patients
      express Abs that bind double-stranded DNA. Recent work has shown that a subset of
      lupus Abs can crossreact with the NR2A and NR2B subunits of the NMDA receptor.
      This receptor is expressed in neurons throughout the brain but is at highest
      density within cells of the hippocampus, amygdala, and hypothalamus. The neurons
      in the CNS are normally protected from brain-reactive Abs by the blood-brain
      barrier (BBB); however, a breach in the barrier's integrity exposes neurons to
      potentially pathogenic Abs. Previously, we have shown that mice that are
      immunized with a peptide mimetope of DNA produce lupus-like Abs that crossreact
      with DNA and the NMDA receptor. Moreover, after abrogation of the BBB by
      treatment with lipopolysaccharide, the immunized mice display hippocampal neuron
      damage with ensuing memory impairment. Given that rises in epinephrine can
      increase cerebral blood flow and can cause leaks in the BBB, we decided to
      investigate whether epinephrine could act as a permissive agent for Ab-mediated
      neurotoxicity. Here, we show that peptide-immunized mice, given epinephrine to
      open the BBB, lose neurons in the lateral amygdala and develop a behavioral
      disorder characterized by a deficient response to fear-conditioning paradigms.
      Thus, the agent used to open the BBB determines which brain region is made
      vulnerable to neurotoxic Abs, and Abs that penetrate brain tissue can cause
      changes not only in cognitive competence, but also in emotional behavior.

PMID- 16407106
TI  - Molecular analysis of the bacterial microbiota in the human stomach.
AB  - The microbiota of the human stomach and the influence of Helicobacter pylori
      colonization on its composition remain largely unknown. We characterized
      bacterial diversity within the human gastric mucosa by using a small subunit 16S
      rDNA clone library approach and analyzed 1,833 sequences generated by broad-range
      bacterial PCR from 23 gastric endoscopic biopsy samples. A diverse community of
      128 phylotypes was identified, featuring diversity at this site greater than
      previously described. The majority of sequences were assigned to the
      Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria
      phyla. Ten percent of the phylotypes were previously uncharacterized, including a
      Deinococcus-related organism, relatives of which have been found in extreme
      environments but not reported before in humans. The gastric clone libraries from
      19 subjects contained H. pylori rDNA; however, only 12 of these subjects tested
      positive for H. pylori by conventional laboratory methods. Statistical analysis
      revealed a large degree of intersubject variability of the gastric ecosystem. The
      presence of H. pylori did not affect the composition of the gastric community.
      This gastric bacterial rDNA data set was significantly different from sequence
      collections of the human mouth and esophagus described in other studies,
      indicating that the human stomach may be home to a distinct microbial eco-system.
      The gastric microbiota may play important, as-yet-undiscovered roles in human
      health and disease.

PMID- 16407107
TI  - Regulation of motor performance and striatal function by synaptic scaffolding
      proteins of the Homer1 family.
AB  - Intracellular calcium mobilization and signaling mechanisms triggered by
      activation of synaptic glutamate receptors in the striatum are important
      modulators of neurotransmission in striatal circuits. However, the expression and
      functions of scaffolding proteins anchoring glutamate receptors at striatal
      synapses have not been addressed so far. The long-form Homer1 proteins,
      Homer1b/c, assemble group I metabotropic glutamate receptors (mGluR1/5) in large
      macromolecular complexes with sources of calcium influx and release at synapses
      as well as with components of the NMDA receptor complex at the neuronal cell
      membrane. Homer1a, the short, activity-dependent splice variant of Homer1b/c,
      lacks the ability of linking mGluR1/5 to synaptic proteins and functions as an
      endogenous negative modulator of the mGluR1/5 inositol 1,4,5-trisphosphate
      receptor signaling complex. We have generated transgenic mice, which overexpress
      Homer1a in striatal medium spiny neurons either homogenously throughout the
      extrastriosomal matrix (Homer1a-matrix line) or predominantly in striosomal
      patches (Homer1a-striosome line). Homer1a-expressing mice demonstrated normal
      development of striatal structure and afferent-efferent connectivity. However,
      motor performance in behavioral tasks and striatal responses to the psychomotor
      stimulant amphetamine were significantly altered in the Homer1a-striosome line.
      Thus, glutamate receptor scaffolding proteins of the Homer1 family critically
      regulate the functions of striatal medium spiny neurons in complex motor tasks
      and its modulation by psychomotor stimulant drugs.

PMID- 16407108
TI  - Ryanodine receptor/calcium release channel PKA phosphorylation: a critical
      mediator of heart failure progression.
AB  - Defective regulation of the cardiac ryanodine receptor (RyR2)/calcium release
      channel, required for excitation-contraction coupling in the heart, has been
      linked to cardiac arrhythmias and heart failure. For example, diastolic calcium
      "leak" via RyR2 channels in the sarcoplasmic reticulum has been identified as an
      important factor contributing to impaired contractility in heart failure and
      ventricular arrhythmias that cause sudden cardiac death. In patients with heart
      failure, chronic activation of the "fight or flight" stress response leads to
      protein kinase A (PKA) hyperphosphorylation of RyR2 at Ser-2808. PKA
      phosphorylation of RyR2 Ser-2808 reduces the binding affinity of the channel
      stabilizing subunit calstabin2, resulting in leaky RyR2 channels. We developed
      RyR2-S2808A mice to determine whether Ser-2808 is the functional PKA
      phosphorylation site on RyR2. Furthermore, mice in which the RyR2 channel cannot
      be PKA phosphorylated were relatively protected against the development of heart
      failure after myocardial infarction. Taken together, these data show that PKA
      phosphorylation of Ser-2808 on the RyR2 channel appears to be a critical mediator
      of progressive cardiac dysfunction after myocardial infarction.

PMID- 16407109
TI  - Osmotic stress mechanically perturbs chemoreceptors in Escherichia coli.
AB  - Two-component signaling systems play a major role in the long-term adaptation of
      microorganisms to changes in osmolarity, but how osmoreceptors work is not well
      understood. Temporal changes in solute concentration are sensed by the chemotaxis
      system in Escherichia coli, enabling these bacteria to avoid regions of high
      osmolarity. To study how osmolarity is detected in this system, we fused yellow
      fluorescent protein (YFP) to the C terminus of the serine or aspartate
      chemoreceptor, monitored the steady-state fluorescence polarization of YFP, and
      found that the polarization decreased substantially upon addition of osmotic
      agents. This decrease was due to an increase in fluorescence resonance energy
      transfer between YFP fluorophores in adjacent homodimers within trimers of
      dimers. Thus, changes in homodimer spacing and/or orientation appear to initiate
      osmotactic signaling.

PMID- 16407110
TI  - Declarative memory consolidation in humans: a prospective functional magnetic
      resonance imaging study.
AB  - Retrieval of recently acquired declarative memories depends on the hippocampus,
      but with time, retrieval is increasingly sustainable by neocortical
      representations alone. This process has been conceptualized as system-level
      consolidation. Using functional magnetic resonance imaging, we assessed over the
      course of three months how consolidation affects the neural correlates of memory
      retrieval. The duration of slow-wave sleep during a nap/rest period after the
      initial study session and before the first scan session on day 1 correlated
      positively with recognition memory performance for items studied before the nap
      and negatively with hippocampal activity associated with correct confident
      recognition. Over the course of the entire study, hippocampal activity for
      correct confident recognition continued to decrease, whereas activity in a
      ventral medial prefrontal region increased. These findings, together with data
      obtained in rodents, may prompt a revision of classical consolidation theory,
      incorporating a transfer of putative linking nodes from hippocampal to prelimbic
      prefrontal areas.

PMID- 16407111
TI  - A landscape effect in tenosynovial giant-cell tumor from activation of CSF1
      expression by a translocation in a minority of tumor cells.
AB  - Tenosynovial giant-cell tumor (TGCT) and pigmented villonodular synovitis (PVNS)
      are related conditions with features of both reactive inflammatory disorders and
      clonal neoplastic proliferations. Chromosomal translocations involving chromosome
      1p13 have been reported in both TGCT and PVNS. We confirm that translocations
      involving 1p13 are present in a majority of cases of TGCT and PVNS and show that
      CSF1 is the gene at the chromosome 1p13 breakpoint. In some cases of both TGCT
      and PVNS, CSF1 is fused to COL6A3 (2q35). The CSF1 translocations result in
      overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it
      is present in a minority of the intratumoral cells, leading to CSF1 expression
      only in these cells, whereas the majority of cells express CSF1R but not CSF1,
      suggesting a tumor-landscaping effect with aberrant CSF1 expression in the
      neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells
      that form a tumorous mass.

PMID- 16407112
TI  - The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite
      proliferation and spreading by macrophage-dependent mechanisms.
AB  - Toxoplasmosis is a healthcare problem in pregnant women and immunocompromised
      patients. Like humans, rats usually develop a subclinical chronic infection. LEW
      rats exhibit total resistance to Toxoplasma gondii infection, which is expressed
      in a dominant mode. A genome-wide search carried out in a cohort of F(2) progeny
      of susceptible BN and resistant LEW rats led to identify on chromosome 10 a major
      locus of control, which we called Toxo1. Using reciprocal BN and LEW lines
      congenic for chromosome 10 genomic regions from the other strain, Toxo1 was found
      to govern the issue of T. gondii infection whatever the remaining genome.
      Analyzes of rats characterized by genomic recombination within Toxo1, reduced the
      interval down to a 1.7-cM region syntenic to human 17p13. In vitro studies showed
      that the Toxo1-mediated refractoriness to T. gondii infection is associated with
      the ability of the macrophage to impede the proliferation of the parasite within
      the parasitophorous vacuole. In contrast, proliferation was observed in
      fibroblasts whatever the genomic origin of Toxo1. Furthermore, ex vivo studies
      indicate that macrophage controls parasitic infection spreading by a Toxo1
      mediated mechanism. This forward genetics approach should ultimately unravel a
      major pathway of innate resistance to toxoplasmosis and possibly to other
      apicomplexan parasitic diseases.

PMID- 16407113
TI  - Mitochondrial DNA mutations are established in human colonic stem cells, and
      mutated clones expand by crypt fission.
AB  - The understanding of the fixation of mutations within human tissues and their
      subsequent clonal expansion is a considerable problem, of which little is known.
      We have previously shown that nononcogenic mutations in the mitochondrial genome
      occur in one of a number of morphologically normal colonic crypt stem cells, the
      progeny of which later occupy the whole crypt. We propose that these wholly
      mutated crypts then clonally expand by crypt fission, where each crypt divides
      into two mutated daughter crypts. Here we show that (i) mutated crypts in the
      process of fission share the same mutated mitochondrial genotype not present in
      neighboring cytochrome c oxidase-positive crypts (the odds of this being a random
      event are >or=2.48 x 10(9):1); (ii) neighboring mutated crypts have the same
      genotype, which is different from adjacent cytochrome c oxidase-positive crypts;
      (iii) mutated crypts are clustered together throughout the colon; and (iv)
      patches of cytochrome c oxidase-deficient crypts increase in size with age. We
      thus demonstrate definitively that crypt fission is the mechanism by which
      mutations spread in the normal human colon. This has important implications for
      the biology of the normal adult human colon and possibly for the growth and
      spread of colorectal neoplasms.

PMID- 16407114
TI  - Discovery of a reaction intermediate of aliphatic aldoxime dehydratase involving
      heme as an active center.
AB  - Recently, we discovered an intriguing hemoprotein [aliphatic aldoxime dehydratase
      (OxdA)] that catalyzes the dehydration of aliphatic aldoximes [R-CH=N-OH] to the
      corresponding nitriles [R-C identical withN] in the industrial Pseudomonas
      chlororaphis B23 strain. Unlike the utilization of H(2)O(2) or O(2) as a mediator
      of the catalysis by other heme-containing enzymes (e.g., P450), OxdA is notable
      for the direct binding of a substrate to the heme iron, experimental evidence of
      which was obtained here by means of resonance Raman (RR) analysis with an isotope
      technique. We found that the addition of a large amount of butyraldoxime (final
      concentration, 200 mM) to ferrous OxdA with a low enzyme concentration (final
      concentration, 5 muM) yields a long-lived OxdA-substrate complex (named OS-II),
      whose UV-vis spectrum is different from the corresponding spectra of the OxdA
      substrate complex I and CO-bound, ferrous, and ferric forms of OxdA.
      Intriguingly, the RR analysis demonstrated that OS-II includes a highly oxidized
      heme with strong bonding between a substrate and the heme iron, as judged from
      the heme oxidation state marker nu(4) band at 1,379 cm(-1) and the (15)N-isotope
      substituted butyraldoxime sensitive band at 857 cm(-1) in the RR spectra. It is
      noteworthy that OS-II has a highly oxidized heme like the ferryl-oxo heme species
      (e.g., compound II) formed by some general hemoproteins, although the function of
      OxdA is different from those (transport of electrons, transport of oxygen,
      sensing of oxygen or carbon monoxide, and catalysis of redox reactions) of
      general hemoproteins.

PMID- 16407115
TI  - Experiment and theory for heterogeneous nucleation of protein crystals in a
      porous medium.
AB  - The determination of high-resolution structures of proteins requires crystals of
      suitable quality. Because of the new impetus given to structural biology by
      structural genomics/proteomics, the problem of crystallizing proteins is becoming
      increasingly acute. There is therefore an urgent requirement for the development
      of new efficient methods to aid crystal growth. Nucleation is the crucial step
      that determines the entire crystallization process. Hence, the holy grail is to
      design a "universal nucleant," a substrate that induces the nucleation of
      crystals of any protein. We report a theory for nucleation on disordered porous
      media and its experimental testing and validation using a mesoporous bioactive
      gel-glass. This material induced the crystallization of the largest number of
      proteins ever crystallized using a single nucleant. The combination of the model
      and the experimental results opens up the scope for the rational design of
      nucleants, leading to alternative means of controlling crystallization.

PMID- 16407116
TI  - Cyclin-dependent kinase 5 activity regulates pain signaling.
AB  - Several molecules and cellular pathways have been implicated in nociceptive
      signaling, but their precise molecular mechanisms have not been clearly defined.
      Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase
      implicated in the development and disease of the mammalian nervous system. The
      precise role of this kinase in sensory pathways has not been well characterized.
      Here we report a molecular role for Cdk5 in nociception. We identified the
      expression of Cdk5 and its activator p35 in nociceptive neurons, which is
      modulated during a peripheral inflammatory response. Increased calpain activity
      in sensory neurons after inflammation resulted in the cleavage of p35 to p25,
      which forms a more stable complex with Cdk5 and, consequently, leads to elevation
      of Cdk5 activity. p35 knockout mice (p35(-/-)), which exhibit significantly
      decreased Cdk5 activity, showed delayed responses to painful thermal stimulation
      compared with WT controls. In contrast, mice overexpressing p35, which exhibit
      elevated levels of Cdk5 activity, were more sensitive to painful thermal stimuli
      than were controls. In conclusion, our data demonstrate a role for Cdk5/p35
      activity in primary afferent nociceptive signaling, suggesting that Cdk5/p35 may
      be a target for the development of analgesic drugs.

PMID- 16407117
TI  - Antagonistic effect of CCAAT enhancer-binding protein-alpha and Pax5 in myeloid
      or lymphoid lineage choice in common lymphoid progenitors.
AB  - Lymphoid lineage-committed progenitors, such as common lymphoid progenitors
      (CLPs), maintain a latent myeloid differentiation potential, which can be
      initiated by stimulation through exogenously expressed cytokine receptors,
      including IL-2 receptors. Here we show that the transcription factor CCAAT
      enhancer-binding protein-alpha (C/EBPalpha) is promptly up-regulated in CLPs upon
      ectopic IL-2 stimulation. Enforced C/EBPalpha expression is sufficient to
      initiate myeloid differentiation from CLPs, as well as from proT and proB cells,
      even though proB cells do not give rise to myeloid cells after ectopic IL-2
      stimulation. Expression of Pax5, a B lymphoid-affiliated transcription factor, is
      completely suppressed by enforced C/EBPalpha but not by ectopic IL-2 stimulation
      in proB cells. Introduction of Pax5 blocks ectopic IL-2 receptor-mediated myeloid
      lineage conversion in CLPs. These data suggest that C/EBPalpha is a proximal
      target of cytokine-induced lineage conversion in lymphoid progenitors.
      Furthermore, complete loss of Pax5 expression triggered by up-regulation of
      C/EBPalpha is a critical event for lineage conversion from lymphoid to myeloid
      lineage in CLPs and proB cells.

PMID- 16407118
TI  - Natural variation and genetic covariance in adult hippocampal neurogenesis.
AB  - Adult hippocampal neurogenesis is highly variable and heritable among laboratory
      strains of mice. Adult neurogenesis is also remarkably plastic and can be
      modulated by environment and activity. Here, we provide a systematic quantitative
      analysis of adult hippocampal neurogenesis in two large genetic reference panels
      of recombinant inbred strains (BXD and AXB/BXA, n = 52 strains). We combined data
      on variation in neurogenesis with a new transcriptome database to extract a set
      of 190 genes with expression patterns that are also highly variable and that
      covary with rates of (i) cell proliferation, (ii) cell survival, or the numbers
      of surviving (iii) new neurons, and (iv) astrocytes. Expression of a subset of
      these neurogenesis-associated transcripts was controlled in cis across the BXD
      set. These self-modulating genes are particularly interesting candidates to
      control neurogenesis. Among these were musashi (Msi1h) and prominin1/CD133
      (Prom1), both of which are linked to stem-cell maintenance and division. Twelve
      neurogenesis-associated transcripts had significant cis-acting quantitative trait
      loci, and, of these, six had plausible biological association with adult
      neurogenesis (Prom1, Ssbp2, Kcnq2, Ndufs2, Camk4, and Kcnj9). Only one cis-acting
      candidate was linked to both neurogenesis and gliogenesis, Rapgef6, a downstream
      target of ras signaling. The use of genetic reference panels coupled with
      phenotyping and global transcriptome profiling thus allowed insight into the
      complexity of the genetic control of adult neurogenesis.

PMID- 16407119
TI  - Serotonin 1A receptors in the living brain of Alzheimer's disease patients.
AB  - 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2
      pyridinyl)benzamide, a selective serotonin 1A (5-HT(1A)) molecular imaging probe,
      was used in conjunction with positron emission tomography (PET) for
      quantification of 5-HT(1A) receptor densities in the living brains of Alzheimer's
      disease patients (ADs) (n = 8), subjects with mild cognitive impairment (n = 6),
      and controls (n = 5). ADs had receptor densities significantly decreased in both
      hippocampi (binding potential: controls 1.62 +/- 0.07; ADs 1.18 +/- 0.26) and
      also in raphe nuclei (controls 0.63 +/- 0.09; ADs 0.37 +/- 0.20). When volume
      losses are included, 5-HT(1A) losses are even more severe (i.e., average mean
      decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong
      correlation of 5-HT(1A) receptor decreases in hippocampus with worsening of
      clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these
      decreases in 5-HT(1A) receptor measures correlate with decreased glucose
      utilization as measured with 2-deoxy-2-[F-18]fluoro-d-glucose PET in the brains
      of ADs (standardized uptake values; globally: controls 0.89 +/- 0.04, ADs 0.72 +/
      0.04; posterior cingulate gyrus: controls 1.05 +/- 0.09, ADs 0.79 +/- 0.11).
      They also inversely correlate with increased neuropathological loads measured
      with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2
      naphthyl}ethylidene)malononitrile PET in several neocortical regions in the same
      subjects. The in vivo observations were confirmed independently by in vitro
      digital autoradiography with 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl}-N-(2-pyridinyl)benzamide and 2-(1-{6-[(2-[F
      18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile on brain
      tissue specimens from two ADs and three nondemented subjects.

PMID- 16407120
TI  - ATRIP associates with replication protein A-coated ssDNA through multiple
      interactions.
AB  - The ATR (ATM- and rad3-related)-mediated checkpoint pathway has a crucial role in
      regulating the cellular responses to DNA damage and DNA-replication stress. ATRIP
      (ATR-interacting protein), the regulatory partner of ATR, binds directly to
      replication protein A (RPA)-coated ssDNA and enables the ATR-ATRIP complex to
      recognize this DNA damage-induced structure. Here, we show that ATRIP associates
      with RPA-ssDNA through multiple interactions. Two major RPA-ssDNA-interacting
      domains of ATRIP were mapped to the regions flanking the conserved coiled-coil
      domain. In contrast to a recent article, we found that ATRIP mutants lacking the
      N terminus retained the ability to bind to RPA-ssDNA, suggesting that the
      multiple interactions between ATRIP and RPA-ssDNA may function redundantly in the
      recruitment of ATR-ATRIP. Unexpectedly, one internal region of ATRIP exhibited
      affinity to ssDNA, suggesting that ATRIP may interact with ssDNA in the ATRIP-RPA
      ssDNA complex. Also, the N terminus of ATRIP associated with RPA-ssDNA in two
      distinct ways, indicating a dynamic and regulated association between ATRIP and
      RPA-ssDNA.

PMID- 16407121
TI  - Fast track to the medial prefrontal cortex.

PMID- 16407122
TI  - Imaging membrane potential in dendritic spines.
AB  - Dendritic spines mediate most excitatory inputs in the brain. Although it is
      clear that spines compartmentalize calcium, it is still unknown what role, if
      any, they play in integrating synaptic inputs. To investigate the electrical
      function of spines directly, we used second harmonic generation (SHG) imaging of
      membrane potential in pyramidal neurons from hippocampal cultures and neocortical
      brain slices. With FM 4-64 as an intracellular SHG chromophore, we imaged
      membrane potential in the soma, dendritic branches, and spines. The SHG response
      to voltage was linear and seemed based on an electro-optic mechanism. The SHG
      sensitivity of the chromophore in spines was similar to that of the parent
      dendritic shaft and the soma. Backpropagation of somatic action potentials
      generated SHG signals at spines with similar amplitude and kinetics to somatic
      ones. Our optical measurements of membrane potential from spines demonstrate
      directly that backpropagating action potentials invade the spines.

PMID- 16407123
TI  - TAF7: a possible transcription initiation check-point regulator.
AB  - Transcription consists of a series of highly regulated steps: assembly of a
      preinitiation complex (PIC) at the promoter nucleated by TFIID, followed by
      initiation, elongation, and termination. The present study has focused on the
      role of the TFIID component, TAF7, in regulating transcription initiation. In
      TFIID, TAF7 binds to TAF1 and inhibits its intrinsic acetyl transferase activity.
      We now report that although TAF7 remains bound to TAF1 and associated with TFIID
      during the formation of the PIC, TAF7 dissociates from the PIC upon transcription
      initiation. Entry of polymerase II into the assembling PIC is associated with
      TAF1 and TAF7 phosphorylation, coincident with TAF7 release. We propose that the
      TFIID composition is dynamic and that TAF7 functions as a check-point regulator
      suppressing premature transcription initiation until PIC assembly is complete.

PMID- 16407124
TI  - Phytochelatin synthase, papain's cousin, in stereo.

PMID- 16407125
TI  - Human medullary responses to cooling and rewarming the skin: a functional MRI
      study.
AB  - A fall in skin temperature precipitates a repertoire of thermoregulatory
      responses that reduce the likelihood of a decrease in core temperature. Studies
      in animals suggest that medullary raphe neurons are essential for cold-defense,
      mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient
      cooling; however, the involvement of raphe neurons in human thermoregulation has
      not been investigated. This study used functional MRI with an anatomically guided
      region of interest (ROI) approach to characterize changes in the blood oxygen
      level-dependent (BOLD) signal within the human medulla of nine normal subjects
      during non-noxious cooling and rewarming of the skin by a water-perfused body
      suit. An ROI covering 4.9 +/- 0.3 mm(2) in the ventral midline of the medulla
      immediately caudal to the pons (the rostral medullary raphe) showed an increase
      in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with
      other times. Overall, that signal showed a strong inverse correlation (R = 0.48,
      P < 0.001) with skin temperature. A larger ROI covering the internal medullary
      cross section at the same level (area, 126 +/- 15 mm(2)) showed no significant
      change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings
      demonstrate that human rostral medullary raphe neurons are selectively activated
      in response to a thermoregulatory challenge and point to the location of
      thermoregulatory neurons homologous to those of the raphe pallidus nucleus in
      rodents.

PMID- 16407126
TI  - P versus Q: structural reaction coordinates capture protein folding on smooth
      landscapes.
AB  - Minding your p's and q's has become as important to protein-folding theorists as
      it is for those being instructed in the rules of etiquette. To assess the quality
      of structural reaction coordinates in predicting the transition-state ensemble
      (TSE) of protein folding, we benchmarked the accuracy of four structural reaction
      coordinates against the kinetic measure P(fold), whose value of 0.50 defines the
      stochastic separatrix for a two-state folding mechanism. For two proteins that
      fold by a simple two-state mechanism, c-src SH3 and CI-2, the Phi-values of the
      TSEs predicted by native topology-based reaction coordinates (including Q, the
      fraction of native contacts) are almost identical to those of the TSE based on
      P(fold), with correlation coefficients of >0.90. For proteins with complex
      folding mechanisms that have especially broad, asymmetrical free energy barriers
      such as the designed 3-ankyrin repeating protein (3ANK) or proteins with distinct
      intermediates such as cyanovirin-N (CV-N), we show that the ensemble of
      structures with P(fold) = 0.50 generally does not include the chemically relevant
      transition states. This weakness of P(fold) limits its usefulness in protein
      folding studies. For such systems, elucidating the essential features of folding
      mechanisms requires using multiple reaction coordinates, although the number is
      still rather small. At the same time, for simple folding mechanisms, there is no
      indication of superiority for P(fold) over structurally chosen and
      thermodynamically relevant reaction coordinates that correctly measure the degree
      of nativeness.

PMID- 16407127
TI  - ChxR is a transcriptional activator in Chlamydia.
AB  - Chlamydia spp. are obligate intracellular bacterial pathogens that alternate
      between two metabolically and morphologically distinct developmental forms, and
      differentiation depends on transcriptional regulation. Genome sequencing of
      Chlamydia trachomatis revealed an ORF, CT630 (chxR), whose amino acid sequence
      contains a winged helix-turn-helix motif similar to the DNA-binding domain of
      response regulators in the OmpR subfamily. ChxR differs from many response
      regulators in that essential residues in the receiver or phosphorylation domain
      are lacking. ChxR functions as a transcriptional regulator because it activated
      transcription of ompF and ompC when expressed in Escherichia coli. In vitro
      transcription combined with microarray analysis also demonstrated that ChxR
      activates its own expression by binding directly to sites upstream of chxR; it
      also activates infA, tufA, oppA, and CT084. DNase I protection studies showed
      that ChxR bound to sites in the ompF and ompC promoter proximal regions that
      overlap but were distinct from OmpR binding sites. Both proteins could bind
      simultaneously to their nonoverlapping binding sites. This report identifies a
      stage-specific transcriptional regulator and some of its target genes in
      Chlamydia.

PMID- 16407128
TI  - CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor
      Emi2/XErp1 to trigger its destruction and meiotic exit.
AB  - In vertebrate meiosis, unfertilized eggs are arrested in metaphase II by
      cytostatic factor (CSF), which is required to maintain mitotic cyclin-dependent
      kinase activity. Fertilization triggers a transient increase in cytosolic free
      Ca(2+), which leads to CSF inactivation and ubiquitin-dependent cyclin
      destruction through the anaphase promoting complex or cyclosome (APC/C). The
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the Polo-like kinase
      Plx1 are essential factors for Ca(2+)-induced meiotic exit, but the critical
      targets of these kinases were unknown. The APC/C inhibitor Emi2 or XErp1 has
      recently been characterized as a pivotal CSF component, required to maintain
      metaphase II arrest and rapidly destroyed in response to Ca(2+) signaling through
      phosphorylation by Plx1 and ubiquitination by the SCF(betaTrCP) complex. An
      important question is how the increase in free Ca(2+) targets Plx1 activity
      toward Emi2. Here, we demonstrate that CaMKII is required for Ca(2+)-induced Emi2
      destruction, and that CaMKII functions as a "priming kinase," directly
      phosphorylating Emi2 at a specific motif to induce a strong interaction with the
      Polo Box domain of Plx1. We show that the strict requirement for CaMKII to
      phosphorylate Emi2 is a specific feature of CSF arrest, and we also use
      phosphatase inhibitors to demonstrate an additional mode of Emi2 inactivation
      independent of its destruction. We firmly establish the CSF component Emi2 as the
      first-known critical and direct target of CaMKII in CSF release, providing a
      detailed molecular mechanism explaining how CaMKII and Plx1 coordinately direct
      APC/C activation and meiotic exit upon fertilization.

PMID- 16407129
TI  - Manganese(II), iron(II), cobalt(II), and copper(II) complexes of an extended
      inherently chiral tris-bipyridyl cage.
AB  - Manganese(II), iron(II), cobalt(II), and copper(II) derivatives of two inherently
      chiral, Tris(bipyridyl) cages (L and L') of type [ML]-(PF(6))(2)(solvent)(n) and
      [FeL'](ClO(4))(2) are reported, where L is the hexa-tertiary butyl-substituted
      derivative of L'. These products were obtained by using the free cage and metal
      template procedures; the latter involved the reductive amination of the
      respective Tris-dialdehyde precursor complexes of iron(II), cobalt(II), or
      nickel(II). Electrochemical, EPR, and NMR studies have been used to probe the
      nature of the individual complexes. X-ray structures of the manganese(II),
      iron(II), and copper(II) complexes of L and the iron(II) complex of L' are
      presented; these are compared with the previously reported structures of the
      corresponding nickel(II) complex and metal-free cage (L). In each complex the
      metal cation occupies the cage's central cavity and is coordinated to six
      nitrogens from the three bipyridyl groups. The cations [MnL](2+) and [FeL](2+)
      are isostructural but both exhibit a different arrangement of the bound cage to
      that observed in the corresponding nickel(II) and copper(II) complexes. The
      latter have an exo-exo arrangement of the bridgehead nitrogen lone pairs, with
      the metal inducing a triple helical twist that extends approximately 22 A along
      the axial length of each complex. In contrast, [MnL](2+) and [FeL](2+) have their
      terminal nitrogen lone pairs directed endo, causing a significant change in the
      configuration of the bound ligand. In [FeL'](2+), the cage has both bridgehead
      nitrogen lone pairs orientated exo. Semiempirical calculations indicate that the
      observed endo-endo and exo-exo arrangements are of comparable energy.

PMID- 16407130
TI  - A family with erythrocytosis establishes a role for prolyl hydroxylase domain
      protein 2 in oxygen homeostasis.
AB  - The number of red blood cells is normally tightly regulated by a classic
      homeostatic mechanism based on oxygen sensing in the kidney. Decreased oxygen
      delivery resulting from anemia induces the production of erythropoietin, which
      increases red cell production and hence oxygen delivery. Investigations of
      erythropoietin regulation identified the transcription factor hypoxia-inducible
      factor (HIF). HIF is now recognized as being a key regulator of genes that
      function in a comprehensive range of processes besides erythropoiesis, including
      energy metabolism and angiogenesis. HIF itself is regulated through the alpha
      subunit, which is hydroxylated in the presence of oxygen by a family of three
      prolyl hydroxylase domain proteins (PHDs)/HIF prolyl hydroxylases/egg-laying
      defective nine enzymes. Hydroxylation allows capture by the von Hippel-Lindau
      tumor suppressor gene product, ubiquitination, and destruction by the proteasome.
      Here we describe an inherited mutation in a mammalian PHD enzyme. We show that
      this mutation in PHD2 results in a marked decrease in enzyme activity and is
      associated with familial erythrocytosis, identifying a previously unrecognized
      cause of this condition. Our findings indicate that PHD2 is critical for normal
      regulation of HIF in humans.

PMID- 16407131
TI  - Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection.
AB  - Immature dendritic cells (DCs) capture HIV type 1 (HIV-1) and can transmit
      captured virus particles to T cells. In this report, we show that HIV-1 particles
      captured by DCs can be transmitted to T cells by exocytosis without de novo
      infection. Captured HIV-1 particles were rapidly endocytosed to tetraspan protein
      (CD9, CD63)-positive endocytic compartments that were reminiscent of
      multivesicular endosomal bodies. Furthermore, some of the endocytosed virus
      particles were constitutively released into the extracellular milieu in
      association with HLA-DR1(+), CD1b(+), CD9(+), and CD63(+) vesicles (exosomes) and
      could initiate productive infections of CD4(+) target cells. Surprisingly, the
      exocytosed vesicle-associated HIV-1 particles from DCs were 10-fold more
      infectious on a perparticle basis than cell-free virus particles. These studies
      describe a previously undescribed mechanism of DC-mediated HIV-1 transmission and
      suggest that virus particle trafficking to multivesicular endosomal bodies and
      subsequent exocytosis can provide HIV-1 particles captured by DCs an avenue for
      immune escape.

PMID- 16407132
TI  - Dual strategies for peptidoglycan discrimination by peptidoglycan recognition
      proteins (PGRPs).
AB  - The innate immune system constitutes the first line of defense against
      microorganisms in both vertebrates and invertebrates. Although much progress has
      been made toward identifying key receptors and understanding their role in host
      defense, far less is known about how these receptors recognize microbial ligands.
      Such studies have been severely hampered by the need to purify ligands from
      microbial sources and a reliance on biological assays, rather than direct
      binding, to monitor recognition. We used synthetic peptidoglycan (PGN)
      derivatives, combined with microcalorimetry, to define the binding specificities
      of human and insect peptidoglycan recognition proteins (PGRPs). We demonstrate
      that these innate immune receptors use dual strategies to distinguish between
      PGNs from different bacteria: one based on the composition of the PGN peptide
      stem and another that senses the peptide bridge crosslinking the stems. To
      pinpoint the site of PGRPs that mediates discrimination, we engineered structure
      based variants having altered PGN-binding properties. The plasticity of the PGRP
      binding site revealed by these mutants suggests an intrinsic capacity of the
      innate immune system to rapidly evolve specificities to meet new microbial
      challenges.

PMID- 16407133
TI  - HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T
      cell leukemia cells.
AB  - Human T cell leukemia virus type I (HTLV-I) causes adult T cell leukemia (ATL) in
      2-5% of carriers after a long latent period. An HTLV-I encoded protein, Tax,
      induces proliferation and inhibits apoptosis, resulting in clonal proliferation
      of infected cells. However, tax gene expression in ATL cells is disrupted by
      several mechanisms, including genetic changes in the tax gene and DNA
      methylation/deletion of the 5' long terminal repeat (LTR). Because Tax is the
      major target of cytotoxic T-lymphocytes in vivo, loss of Tax expression should
      enable ATL cells to escape the host immune system. The 5' LTR of HTLV-I is
      frequently hypermethylated or deleted in ATL cells, whereas the 3' LTR remains
      unmethylated and intact, suggesting the involvement of the 3' LTR in
      leukemogenesis. Here we show that a gene encoded by the minus strand of the HTLV
      I proviral genome, HTLV-I basic leucine zipper factor (HBZ), is transcribed from
      3'-LTR in all ATL cells. Suppression of HBZ gene transcription by short
      interfering RNA inhibits proliferation of ATL cells. In addition, HBZ gene
      expression promotes proliferation of a human T cell line. Analyses of T cell
      lines transfected with mutated HBZ genes showed that HBZ promotes T cell
      proliferation in its RNA form, whereas HBZ protein suppresses Tax-mediated viral
      transcription through the 5' LTR. Thus, the single HBZ gene has bimodal functions
      in two different molecular forms. The growth-promoting activity of HBZ RNA likely
      plays an important role in oncogenesis by HTLV-I.

PMID- 16407134
TI  - Retrotransposon insertion in SILV is responsible for merle patterning of the
      domestic dog.
AB  - Merle is a pattern of coloring observed in the coat of the domestic dog and is
      characterized by patches of diluted pigment. This trait is inherited in an
      autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the
      merle locus exhibit a wide range of auditory and ophthalmologic abnormalities,
      which are similar to those observed for the human auditory-pigmentation disorder
      Waardenburg syndrome. Mutations in at least five genes have been identified as
      causative for Waardenburg syndrome; however, the genetic bases for all cases have
      not been determined. Linkage disequilibrium was identified for a microsatellite
      marker with the merle phenotype in the Shetland Sheepdog. The marker is located
      in a region of CFA10 that exhibits conservation of synteny with HSA12q13. This
      region of the human genome contains SILV, a gene important in mammalian
      pigmentation. Therefore, this gene was evaluated as a candidate for merle
      patterning. A short interspersed element insertion at the boundary of intron
      10/exon 11 was found, and this insertion segregates with the merle phenotype in
      multiple breeds. Another finding was deletions within the oligo(dA)-rich tail of
      the short interspersed element. Such deletions permit normal pigmentation. These
      data show that SILV is responsible for merle patterning and is associated with
      impaired function of the auditory and ophthalmologic systems. Although the mutant
      phenotype of SILV in the human is unknown, these results make it an intriguing
      candidate gene for human auditory-pigmentation disorders.

PMID- 16407135
TI  - MgSiO3 postperovskite at D'' conditions.
AB  - The postperovskite transition in MgSiO(3) at conditions similar to those expected
      at the D'' discontinuity of Earth's lower mantle offers a paradigm for
      interpreting the properties of this region. Despite consistent experimental and
      theoretical predictions of this phase transformation, the complexity of the D''
      region raises questions about its geophysical significance. Here we report the
      thermoelastic properties of Cmcm postperovskite at appropriate conditions and
      evidences of its presence in the lowermost mantle. These are (i) the jumps in
      shear and longitudinal velocities similar to those observed in certain places of
      the D'' discontinuity and (ii) the anticorrelation between shear and bulk
      velocity anomalies as detected within the D'' region. In addition, the increase
      in shear modulus across the phase transition provides a possible explanation for
      the reported discrepancy between the calculated shear modulus of postperovskite
      free aggregates and the seismological counterpart in the lowermost mantle.

PMID- 16407136
TI  - Nitric oxide inhibition of respiration involves both competitive (heme) and
      noncompetitive (copper) binding to cytochrome c oxidase.
AB  - NO reversibly inhibits mitochondrial respiration via binding to cytochrome c
      oxidase (CCO). This inhibition has been proposed to be a physiological control
      mechanism and/or to contribute to pathophysiology. Oxygen reacts with CCO at a
      heme iron:copper binuclear center (a(3)/Cu(B)). Reports have variously suggested
      that during inhibition NO can interact with the binuclear center containing zero
      (fully oxidized), one (singly reduced), and two (fully reduced) additional
      electrons. It has also been suggested that two NO molecules can interact with the
      enzyme simultaneously. We used steady-state and kinetic modeling techniques to
      reevaluate NO inhibition of CCO. At high flux and low oxygen tensions NO
      interacts predominantly with the fully reduced (ferrous/cuprous) center in
      competition with oxygen. However, as the oxygen tension is raised (or the
      consumption rate is decreased) the reaction with the oxidized enzyme becomes
      increasingly important. There is no requirement for NO to bind to the singly
      reduced binuclear center. NO interacts with either ferrous heme iron or oxidized
      copper, but not both simultaneously. The affinity (K(D)) of NO for the oxygen
      binding ferrous heme site is 0.2 nM. The noncompetitive interaction with oxidized
      copper results in oxidation of NO to nitrite and behaves kinetically as if it had
      an apparent affinity of 28 nM; at low levels of NO, significant binding to copper
      can occur without appreciable enzyme inhibition. The combination of competitive
      (heme) and noncompetitive (copper) modes of binding enables NO to interact with
      mitochondria across the full in vivo dynamic range of oxygen tension and
      consumption rates.

PMID- 16407137
TI  - The peptidoglycan recognition protein PGRP-SC1a is essential for Toll signaling
      and phagocytosis of Staphylococcus aureus in Drosophila.
AB  - From a forward genetic screen for phagocytosis mutants in Drosophila
      melanogaster, we identified a mutation that affects peptidoglycan recognition
      protein (PGRP) SC1a and impairs the ability to phagocytose the bacteria
      Staphylococcus aureus, but not Escherichia coli and Bacillus subtilis. Because of
      the differences in peptidoglycan peptide linkages in these bacteria, our data
      suggest that PGRP-SC1a is necessary for recognition of the Lys-type peptidoglycan
      typical of most Gram(+) bacteria. PGRP-SC1a mutants also fail to activate the
      Toll/NF-kappaB signaling pathway and are compromised for survival after S. aureus
      infection. This mutant phenotype is the first found for an N-acetylmuramoyl-l
      alanine amidase PGRP that cleaves peptidoglycan at the lactylamide bond between
      the glycan backbone and the crosslinking stem peptides. By generating transgenic
      rescue flies that express either wild-type or a noncatalytic cysteine-serine
      mutant PGRP-SC1a, we find that PGRP-SC1a amidase activity is not necessary for
      Toll signaling, but is essential for uptake of S. aureus into the host phagocytes
      and for survival after S. aureus infection. Furthermore, we find that the PGRP
      SC1a amidase activity can be substituted by exogenous addition of free
      peptidoglycan, suggesting that the presence of peptidoglycan cleavage products is
      more important than the generation of cleaved peptidoglycan on the bacterial
      surface for PGRP-SC1a mediated phagocytosis.

PMID- 16407138
TI  - Xbves is a regulator of epithelial movement during early Xenopus laevis
      development.
AB  - Bves/pop1a is a unique, highly conserved integral membrane protein expressed in
      embryonic epithelia and striated muscle. Although studies have proposed a role in
      epithelial morphogenesis, the function of Bves/pop1a in development is completely
      unknown. Here we show that Xenopus laevis Bves (Xbves) RNA and protein are
      expressed in epithelia of the early embryo. Transfection of Xbves into
      nonadherent mouse L cells confers cell/cell adhesion. Global inhibition of Xbves
      function by morpholino injection into two-cell embryos arrests development at
      gastrulation by deregulating the epithelial movements of epiboly and involution.
      Clonal inhibition of Xbves activity within the A1 blastomere and its derivatives
      completely randomizes movement of its progeny within otherwise normally
      differentiating embryos. These data demonstrate that Bves/pop1a proteins play a
      critical role in epithelial morphogenesis and, specifically, in the cell
      movements essential for epithelial rearrangements that occur during X. laevis
      development.

PMID- 16407139
TI  - Habitat history improves prediction of biodiversity in rainforest fauna.
AB  - Patterns of biological diversity should be interpreted in light of both
      contemporary and historical influences; however, to date, most attempts to
      explain diversity patterns have largely ignored history or have been unable to
      quantify the influence of historical processes. The historical effects on
      patterns of diversity have been hypothesized to be most important for taxonomic
      groups with poor dispersal abilities. We quantified the relative stability of
      rainforests over the late Quaternary period by modeling rainforest expansion and
      contraction in 21 biogeographic subregions in northeast Australia across four
      time periods. We demonstrate that historical habitat stability can be as
      important, and in endemic low-dispersal taxa even more important, than current
      habitat area in explaining spatial patterns of species richness. In contrast,
      patterns of endemic species richness for taxa with high dispersal capacity are
      best predicted by using current environmental parameters. We also show that
      contemporary patterns of species turnover across the region are best explained by
      historical patterns of habitat connectivity. These results clearly demonstrate
      that spatially explicit analyses of the historical processes of persistence and
      colonization are both effective and necessary for understanding observed patterns
      of biodiversity.

PMID- 16407140
TI  - Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic
      [correction of electrophillic] phase II inducers.
AB  - Electrophilic neurite outgrowth-promoting prostaglandin (NEPP) compounds protect
      neurons from oxidative insults. At least part of the neuroprotective action of
      NEPPs lies in induction of hemeoxygenase-1 (HO-1), which, along with other phase
      II enzymes, serve as a defense system against oxidative stress. Here, we found
      that, by using fluorescent tags and immunoprecipitation assays, NEPPs are taken
      up preferentially into neurons and bind in a thiol-dependent manner to Keap1, a
      negative regulator of the transcription factor Nrf2. By binding to Keap1, NEPPs
      prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation
      into the nucleus of cultured neuronal cells. In turn, Nrf2 binds to
      antioxidant/electrophile-responsive elements of the HO-1 promoter to induce HO-1
      expression. Consistent with this notion, NEPP induction of an HO-1 reporter
      construct is prevented if the antioxidant-responsive elements are mutated. We
      show that NEPPs are neuroprotective both in vitro from glutamate-related
      excitotoxicity and in vivo in a model of cerebral ischemia/reperfusion injury
      (stroke). Our results suggest that NEPPs prevent excitotoxicity by activating the
      Keap1/Nrf2/HO-1 pathway. Because NEPPs accumulate preferentially in neurons, they
      may provide a category of neuroprotective compounds, distinct from other
      electrophilic compounds such as tert-butylhydroquinone, which activates the
      antioxidant-responsive element in astrocytes. NEPPs thus represent a therapeutic
      approach for stroke and neurodegenerative disorders.

PMID- 16407141
TI  - On the mechanical behavior of WS2 nanotubes under axial tension and compression.
AB  - The mechanical properties of materials and particularly the strength are greatly
      affected by the presence of defects; therefore, the theoretical strength (
      approximately 10% of the Young's modulus) is not generally achievable for
      macroscopic objects. On the contrary, nanotubes, which are almost defect-free,
      should achieve the theoretical strength that would be reflected in superior
      mechanical properties. In this study, both tensile tests and buckling experiments
      of individual WS(2) nanotubes were carried out in a high-resolution scanning
      electron microscope. Tensile tests of MoS(2) nanotubes were simulated by means of
      a density-functional tight-binding-based molecular dynamics scheme as well. The
      combination of these studies provides a microscopic picture of the nature of the
      fracture process, giving insight to the strength and flexibility of the WS(2)
      nanotubes (tensile strength of approximately 16 GPa). Fracture analysis with
      recently proposed models indicates that the strength of such nanotubes is
      governed by a small number of defects. A fraction of the nanotubes attained the
      theoretical strength indicating absence of defects.

PMID- 16407142
TI  - Peripheral cannabinoid receptor, CB2, regulates bone mass.
AB  - The endogenous cannabinoids bind to and activate two G protein-coupled receptors,
      the predominantly central cannabinoid receptor type 1 (CB1) and peripheral
      cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid
      psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in
      the regulation of liver fibrosis and atherosclerosis. Here we show that CB2
      deficient mice have a markedly accelerated age-related trabecular bone loss and
      cortical expansion, although cortical thickness remains unaltered. These changes
      are reminiscent of human osteoporosis and may result from differential regulation
      of trabecular and cortical bone remodeling. The CB2(-/-) phenotype is also
      characterized by increased activity of trabecular osteoblasts (bone-forming
      cells), increased osteoclast (the bone-resorbing cell) number, and a markedly
      decreased number of diaphyseal osteoblast precursors. CB2 is expressed in
      osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not
      have any psychotropic effects enhances endocortical osteoblast number and
      activity and restrains trabecular osteoclastogenesis, apparently by inhibiting
      proliferation of osteoclast precursors and receptor activator of NF-kappaB ligand
      expression in bone marrow-derived osteoblasts/stromal cells. The same agonist
      attenuates ovariectomy-induced bone loss and markedly stimulates cortical
      thickness through the respective suppression of osteoclast number and stimulation
      of endocortical bone formation. These results demonstrate that the
      endocannabinoid system is essential for the maintenance of normal bone mass by
      osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target
      for the diagnosis and treatment of osteoporosis, the most prevalent degenerative
      disease in developed countries.

PMID- 16407143
TI  - Heterogeneous shedding of Escherichia coli O157 in cattle and its implications
      for control.
AB  - Identification of the relative importance of within- and between-host variability
      in infectiousness and the impact of these heterogeneities on the transmission
      dynamics of infectious agents can enable efficient targeting of control measures.
      Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157,
      are known to exhibit a high degree of heterogeneity in bacterial shedding
      densities. By relating bacterial count to infectiousness and fitting dynamic
      epidemiological models to prevalence data from a cross-sectional survey of cattle
      farms in Scotland, we identify a robust pattern: approximately 80% of the
      transmission arises from the 20% most infectious individuals. We examine
      potential control options under a range of assumptions about within- and between
      host variability in infection dynamics. Our results show that the within-herd
      basic reproduction ratio, R(0), could be reduced to <1 with targeted measures
      aimed at preventing infection in the 5% of individuals with the highest overall
      infectiousness. Alternatively, interventions such as vaccination or the use of
      probiotics that aim to reduce bacterial carriage could produce dramatic
      reductions in R(0) by preventing carriage at concentrations corresponding to the
      top few percent of the observed range of counts. We conclude that a greater
      understanding of the cause of the heterogeneity in bacterial carriage could lead
      to highly efficient control measures to reduce the prevalence of E. coli O157.

PMID- 16407145
TI  - Global spectral representations of black hole spacetimes in the complex plane.
AB  - Binary black hole coalescence produces a finite burst of gravitational radiation,
      which propagates toward quiescent infinity. These spacetimes are analytic about
      infinity and contain a dimensionless coupling constant M/s, where M denotes the
      total mass-energy and s is an imaginary distance. This work introduces a globally
      convergent Fourier series in a complex radial coordinate, allowing spectral
      representations of black hole spacetimes in all three dimensions. This method
      circumvents singularities associated with black holes and includes infinity,
      thereby avoiding the need to impose radiative boundary conditions. We illustrate
      this representation theory on Boyer-Lindquist initial data of two black holes and
      a scalar wave equation with signal recovery by Cauchy's integral formula.

PMID- 16407144
TI  - Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange
      protein directly activated by cAMP (EPAC).
AB  - The Na(+)/H(+) exchanger 3 (NHE3) is expressed in the brush border membrane (BBM)
      of proximal tubules (PT). Its activity is down-regulated on increases in
      intracellular cAMP levels. The aim of this study was to investigate the
      contribution of the protein kinase A (PKA) and the exchange protein directly
      activated by cAMP (EPAC) dependent pathways in the regulation of NHE3 by
      adenosine 3',5'-cyclic monophosphate (cAMP). Opossum kidney cells and murine
      kidney slices were treated with cAMP analogs, which selectively activate either
      PKA or EPAC. Activation of either pathway resulted in an inhibition of NHE3
      activity. The EPAC-induced effect was independent of PKA as indicated by the lack
      of activation of the kinase and the insensitivity to the PKA inhibitor H89. Both
      PKA and EPAC inhibited NHE3 activity without inducing changes in the expression
      of the transporter in BBM. Activation of PKA, but not of EPAC, led to an increase
      of NHE3 phosphorylation. In contrast, activation of PKA, but not of EPAC,
      inhibited renal type IIa Na(+)-coupled inorganic phosphate cotransporter (NaPi
      IIa), another Na-dependent transporter expressed in proximal BBM. PKA, but not
      EPAC, induced the retrieval of NaPi-IIa from BBM. Our results suggest that EPAC
      activation may represent a previously unrecognized mechanism involved in the cAMP
      regulation of NHE3, whereas regulation of NaPi-IIa is mediated by PKA but not by
      EPAC.

PMID- 16407146
TI  - Global genetic positioning: evidence for early human population centers in
      coastal habitats.
AB  - For an alternative perspective on relationships among human populations, we
      combined genetic and geographic information, using allele frequency gradients to
      place populations and individuals on the globe. Reanalyzing published data on 51
      worldwide populations [Rosenberg, N. A., Pritchard, J. K., Weber, J. L., Cann, H.
      M., Kidd, K. K., Zhivitovsky, L. A. & Feldman, M. W. (2002) Science 298, 2381
      2385] reveals five geographic clusters lying in plausible sites either of early
      agricultural innovation or on ancient migration routes. Also, the inferred sites
      show significant association with coastlines, suggesting that most early humans
      lived near large bodies of water. Our approach is flexible, and developments
      should prove useful both for exploring historical demography and for the
      identification of likely origin for unknown forensic samples.

PMID- 16407147
TI  - Mammalian alpha I-spectrin is a neofunctionalized polypeptide adapted to small
      highly deformable erythrocytes.
AB  - Mammalian red blood cells, unlike those of other vertebrates, must withstand the
      rigors of circulation in the absence of new protein synthesis. Key to this is
      plasma membrane elasticity deriving from the protein spectrin, which forms a
      network on the cytoplasmic face. Spectrin is a tetramer (alphabeta)(2), made up
      of alphabeta dimers linked head to head. We show here that one component of
      erythrocyte spectrin, alphaI, is encoded by a gene unique to mammals.
      Phylogenetic analysis suggests that the other alpha-spectrin gene (alphaII)
      common to all vertebrates was duplicated after the emergence of amphibia, and
      that the resulting alphaI gene was preserved only in mammals. The activities of
      alphaI and alphaII spectrins differ in the context of the human red cell
      membrane. An alphaI-spectrin fragment containing the site of head-to-head
      interaction with the beta-chain binds more weakly than the corresponding alphaII
      fragment to this site. The latter competes so strongly with endogenous alphaI as
      to cause destabilization of membranes at 100-fold lower concentration than the
      alphaI fragment. The efficacies of alphaI/alphaII chimeras indicate that the
      partial structural repeat, which binds to the complementary beta-spectrin
      element, and the adjacent complete repeat together determine the strength of the
      dimer-dimer interaction on the membrane. Alignment of all available alpha
      spectrin N-terminal sequences reveals three blocks of sequence unique to alphaI.
      Furthermore, human alphaII-spectrin is closer to fruitfly alpha-spectrin than to
      human alphaI-spectrin, consistent with adaptation of alphaI to new functions. We
      conclude that alphaI-spectrin represents a neofunctionalized spectrin adapted to
      the rapid make and break of tetramers.

PMID- 16407148
TI  - The diversity and biogeography of soil bacterial communities.
AB  - For centuries, biologists have studied patterns of plant and animal diversity at
      continental scales. Until recently, similar studies were impossible for
      microorganisms, arguably the most diverse and abundant group of organisms on
      Earth. Here, we present a continental-scale description of soil bacterial
      communities and the environmental factors influencing their biodiversity. We
      collected 98 soil samples from across North and South America and used a
      ribosomal DNA-fingerprinting method to compare bacterial community composition
      and diversity quantitatively across sites. Bacterial diversity was unrelated to
      site temperature, latitude, and other variables that typically predict plant and
      animal diversity, and community composition was largely independent of geographic
      distance. The diversity and richness of soil bacterial communities differed by
      ecosystem type, and these differences could largely be explained by soil pH (r(2)
      = 0.70 and r(2) = 0.58, respectively; P < 0.0001 in both cases). Bacterial
      diversity was highest in neutral soils and lower in acidic soils, with soils from
      the Peruvian Amazon the most acidic and least diverse in our study. Our results
      suggest that microbial biogeography is controlled primarily by edaphic variables
      and differs fundamentally from the biogeography of "macro" organisms.

PMID- 16407150
TI  - Direct measurement of the free energy by optical microscopy.
AB  - We report the direct measurement of thermodynamic properties of colloidal hard
      spheres by optical microscopy. By using confocal microscopy, we obtain three
      dimensional snapshots of a colloidal hard-sphere suspension over a wide range of
      densities. From these snapshots, the available volume to insert an additional
      sphere and the surface area of that volume are determined, which are directly
      related to the thermodynamics of the system. This procedure enables us to measure
      in a direct and noninterfering way, in principle, all thermodynamic properties,
      here demonstrated for the pressure, the chemical potential, and the free-energy
      density of a colloidal hard-sphere suspension. The "visual" determination of
      thermodynamic quantities opens up the possibility to experimentally study the
      relation between thermodynamics and geometry in real space beyond the hard-sphere
      potential.

PMID- 16407149
TI  - Identification of a receptor-independent activator of G protein signaling (AGS8)
      in ischemic heart and its interaction with Gbetagamma.
AB  - As part of a broader effort to identify postreceptor signal regulators involved
      in specific diseases or organ adaptation, we used an expression cloning system in
      Saccharomyces cerevisiae to screen cDNA libraries from rat ischemic myocardium,
      human heart, and a prostate leiomyosarcoma for entities that activated G protein
      signaling in the absence of a G protein coupled receptor. We report the
      characterization of activator of G protein signaling (AGS) 8 (KIAA1866), isolated
      from a rat heart model of repetitive transient ischemia. AGS8 mRNA was induced in
      response to ventricular ischemia but not by tachycardia, hypertrophy, or failure.
      Hypoxia induced AGS8 mRNA in isolated adult ventricular cardiomyocytes but not in
      rat aortic smooth muscle cells, endothelial cells, or cardiac fibroblasts,
      suggesting a myocyte-specific adaptation mechanism involving remodeling of G
      protein signaling pathways. The bioactivity of AGS8 in the yeast-based assay was
      independent of guanine nucleotide exchange by Galpha, suggesting an impact on
      subunit interactions. Subsequent studies indicated that AGS8 interacts directly
      with Gbetagamma and this occurs in a manner that apparently does not alter the
      regulation of the effector PLC-beta(2) by Gbetagamma. Mechanistically, AGS8
      appears to promote G protein signaling by a previously unrecognized mechanism
      that involves direct interaction with Gbetagamma.

PMID- 16407151
TI  - Allosteric changes of the NMDA receptor trap diffusible dopamine 1 receptors in
      spines.
AB  - The dopaminergic and glutamatergic systems interact to initiate and organize
      normal behavior, a communication that may be perturbed in many neuropsychiatric
      diseases, including schizophrenia. We show here that NMDA, by allosterically
      modifying NMDA receptors, can act as a scaffold to recruit laterally diffusing
      dopamine D1 receptors (D1R) to neuronal spines. Using organotypic culture from
      rat striatum transfected with D1R fused to a fluorescent protein, we show that
      the majority of dendritic D1R are in lateral diffusion and that their mobility is
      confined by interaction with NMDA receptors. Exposure to NMDA reduces the
      diffusion coefficient for D1R and causes an increase in the number of D1R
      positive spines. Unexpectedly, the action of NMDA in potentiating D1R recruitment
      was independent of calcium flow via the NMDA receptor channel. Thus, a highly
      energy-efficient, diffusion-trap mechanism can account for intraneuronal
      interaction between the glutamatergic and dopaminergic systems and for regulation
      of the number of D1R-positive spines. This diffusion trap system represents a
      molecular mechanism for brain plasticity and offers a promising target for
      development of antipsychotic therapy.

PMID- 16407152
TI  - Cytokinin-mediated control of leaf longevity by AHK3 through phosphorylation of
      ARR2 in Arabidopsis.
AB  - Cytokinins are plant hormones with profound roles in growth and development,
      including control of leaf longevity. Although the cytokinin signal is known to be
      perceived by histidine kinase receptors, the underlying molecular mechanism and
      specificity of the receptors leading to delayed leaf senescence have not yet been
      elucidated. Here, we found that AHK3, one of the three cytokinin receptors in
      Arabidopsis, plays a major role in controlling cytokinin-mediated leaf longevity
      through a specific phosphorylation of a response regulator, ARR2. This result was
      obtained through identification of a gain-of-function Arabidopsis mutant that
      shows delayed leaf senescence because of a missense mutation in the extracellular
      domain of AHK3. A loss-of-function mutation in AHK3, but not of the other
      cytokinin receptors, conferred a reduced sensitivity to cytokinin in cytokinin
      dependent delay of leaf senescence and abolished cytokinin-dependent
      phosphorylation of ARR2. Consistently, transgenic overexpression of wild-type,
      but not an unphosphorylatable mutant ARR2, led to delayed senescence of leaves.

PMID- 16407153
TI  - Analysis of gene expression in pathophysiological states: balancing false
      discovery and false negative rates.
AB  - Nucleotide-microarray technology, which allows the simultaneous measurement of
      the expression of tens of thousands of genes, has become an important tool in the
      study of disease. In disorders such as malignancy, gene expression often
      undergoes broad changes of sizable magnitude, whereas in many common
      multifactorial diseases, such as diabetes, obesity, and atherosclerosis, the
      changes in gene expression are modest. In the latter circumstance, it is
      therefore challenging to distinguish the truly changing from non-changing genes,
      especially because statistical significance must be considered in the context of
      multiple hypothesis testing. Here, we present a balanced probability analysis
      (BPA), which provides the biologist with an approach to interpret results in the
      context of the total number of genes truly differentially expressed and false
      discovery and false negative rates for the list of genes reaching any
      significance threshold. In situations where the changes are of modest magnitude,
      sole consideration of the false discovery rate can result in poor power to detect
      genes truly differentially expressed. Concomitant analysis of the rate of truly
      differentially expressed genes not identified, i.e., the false negative rate,
      allows balancing of the two error rates and a more thorough insight into the
      data. To this end, we have developed a unique, model-based procedure for the
      estimation of false negative rates, which allows application of BPA to real data
      in which changes are modest.

PMID- 16407154
TI  - mGluR7's lucky number.

PMID- 16407155
TI  - Primary steps of the photoactive yellow protein: isolated chromophore dynamics
      and protein directed function.
AB  - The cycle of the photoactive yellow protein (PYP) has been extensively studied,
      but the dynamics of the isolated chromophore responsible for transduction is
      unknown. Here, we present real-time observation of the dynamics of the negatively
      charged chromophore and detection of intermediates along the path of trans-to-cis
      isomerization using femtosecond mass selection/electron detachment techniques.
      The results show that the role of the protein environment is not in the first
      step of double-bond twisting (barrier crossing) but in directing efficient
      conversion to the cis-structure and in impeding radical formation within the
      protein.

PMID- 16407156
TI  - Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of
      urea, glycerol, ammonia, and protons.
AB  - Water-specific aquaporins (AQP), such as the prototypical mammalian AQP1,
      stringently exclude the passage of solutes, ions, and even protons. Supposedly,
      this is accomplished by two conserved regions within the pore, a pair of
      canonical asparagine-proline-alanine (NPA) motifs, the central constriction, and
      an aromatic/arginine (ar/R) constriction, the outer constriction. Here, we
      analyzed the function of three residues in the ar/R constriction (Phe-56, His
      180, and Arg-195) in rat AQP1. Individual or joint replacement of His-180 and Arg
      195 by alanine and valine residues, respectively (AQP1-H180A, AQP1-R195V, and
      AQP1-H180A/R195V), did not affect water permeability. The double mutant AQP1
      H180A/R195V allowed urea to pass. In line with the predicted solute
      discrimination by size, replacement of both Phe-56 and His-180 (AQP1-F56A/H180A)
      enlarged the maximal diameter of the ar/R constriction 3-fold and enabled
      glycerol and urea to pass. We further show that ammonia passes through all four
      AQP1 mutants, as determined (i) by growth complementation of yeast deletion
      strains with ammonia, (ii) by ammonia uptake from the external solution into
      oocytes, and (iii) by direct recordings of ammonia induced proton currents in
      oocytes. Unexpectedly, removal of the positive charge in the ar/R constriction in
      AQP1-R195V and AQP1-H180A/R195V appeared to allow the passage of protons through
      AQP1. The data indicate that the ar/R constriction is a major checkpoint for
      solute permeability, and that the exquisite electrostatic proton barrier in AQPs
      comprises both the NPA constriction as well as the ar/R constriction.

PMID- 16407157
TI  - Harnessing the potential of communication-mediating domains for the
      biocombinatorial synthesis of nonribosomal peptides.
AB  - The interaction between enzymes of a nonribosomal peptide synthetase (NRPS)
      complex relies on the interplay of compatible sets of donor and acceptor
      communication-mediating (COM) domains. Hence, these domains are essential for the
      formation of a defined biosynthetic template, thereby directing the synthesis of
      a specific peptide product. Without the selectivity provided by different sets of
      COM domains, NRPSs should form random biosynthetic templates, which would
      ultimately lead to combinatorial peptide synthesis. This study aimed to exploit
      this inherent combinatorial potential of COM domains. Based on sequence
      alignments between COM domains, the crosstalk between different biosynthetic
      systems was predicted and experimentally proven. Furthermore, key residues
      important for maintaining (or preventing) NRPS interaction were identified. Point
      mutation of one of these key residues within the acceptor COM domain of TycC1 was
      sufficient to shift its selectivity from the cognate donor COM of TycB3 toward
      the noncognate donor COM domain of TycB1. Finally, an artificial NRPS complex was
      constructed, constituted of enzymes derived from three different biosynthetic
      systems. By virtue of domain fusions, the interactions between all enzymes were
      established by the same set of COM domains. Because of the abrogated selectivity,
      this universal communication system was able to simultaneously form two
      biosynthetic complexes that catalyzed the combinatorial synthesis of different
      peptide products.

PMID- 16407158
TI  - Generating disulfides enzymatically: reaction products and electron acceptors of
      the endoplasmic reticulum thiol oxidase Ero1p.
AB  - Ero1p is a key enzyme in the disulfide bond formation pathway in eukaryotic cells
      in both aerobic and anaerobic environments. It was previously demonstrated that
      Ero1p can transfer electrons from thiol substrates to molecular oxygen. However,
      the fate of electrons under anaerobic conditions and the final fate of electrons
      under aerobic conditions remained obscure. To address these fundamental issues in
      the Ero1p mechanism, we studied the transfer of electrons from recombinant yeast
      Ero1p to various electron acceptors. Under aerobic conditions, reduction of
      molecular oxygen by Ero1p yielded stoichiometric hydrogen peroxide. Remarkably,
      we found that reduced Ero1p can transfer electrons to a variety of small and
      macromolecular electron acceptors in addition to molecular oxygen. In particular,
      Ero1p can catalyze reduction of exogenous FAD in solution. Free FAD is not
      required for the catalysis of dithiol oxidation by Ero1p, but it is sufficient to
      drive disulfide bond formation under anaerobic conditions. These findings provide
      insight into mechanisms for regenerating oxidized Ero1p and maintaining disulfide
      bond formation under anaerobic conditions in the endoplasmic reticulum.

PMID- 16407159
TI  - Controlled uncoupling and recoupling of proton pumping in cytochrome c oxidase.
AB  - Cytochrome c oxidase (CcO) is the terminal enzyme of the respiratory chain and
      couples energetically the reduction of oxygen to water to proton pumping across
      the membrane. The results from previous studies showed that proton pumping can be
      uncoupled from the O2-reduction reaction by replacement of one single residue,
      Asn-139 by Asp (N139D), located approximately 30 A from the catalytic site, in
      the D-proton pathway. The uncoupling was correlated with an increase in the pK(a)
      of an internal proton donor, Glu-286, from approximately 9.4 to >11. Here, we
      show that replacement of the acidic residue, Asp-132 by Asn in the N139D CcO
      (D132N/N139D double-mutant CcO) results in restoration of the Glu-286 pK(a) to
      the original value and recoupling of the proton pump during steady-state
      turnover. Furthermore, a kinetic investigation of the specific reaction steps in
      the D132N/N139D double-mutant CcO showed that proton pumping is sustained even if
      proton uptake from solution, through the D-pathway, is slowed. However, during
      single-turnover oxidation of the fully reduced CcO the P --> F transition, which
      does not involve electron transfer to the catalytic site, was not coupled to
      proton pumping. The results provide insights into the mechanism of proton pumping
      by CcO and the structural elements involved in this process.

PMID- 16407160
TI  - Phase coexistence and connectivity in the apical membrane of polarized epithelial
      cells.
AB  - Although it is well described in model membranes, little is known about phase
      separation in biological membranes. Here, we provide evidence for a coexistence
      of at least two different lipid bilayer phases in the apical plasma membrane of
      epithelial cells. Phase connectivity was assessed by measuring long-range
      diffusion of several membrane proteins by fluorescence recovery after
      photobleaching in two polarized epithelial cell lines and one fibroblast cell
      line. In contrast to the fibroblast plasma membrane, in which all of the proteins
      diffused with similar characteristics, in the apical membrane of epithelial cells
      the proteins could be divided into two groups according to their diffusion
      characteristics. At room temperature ( approximately 25 degrees C), one group
      showed fast diffusion and complete recovery. The other diffused three to four
      times slower and, more importantly, displayed only partial recovery. Only the
      first group comprises proteins that are believed to be associated with lipid
      rafts. The partial recovery is not caused by topological constraints (microvilli,
      etc.), cytoskeletal constraints, or protein-protein interactions, because all
      proteins show 100% recovery in fluorescence recovery after photobleaching
      experiments at 37 degrees C. In addition, the raft-associated proteins cannot be
      coclustered by antibodies on the apical membrane at 12 degrees C. The
      interpretation that best fits these data is that the apical membrane of
      epithelial cells is a phase-separated system with a continuous (percolating) raft
      phase <25 degrees C in which isolated domains of the nonraft phase are dispersed,
      whereas at 37 degrees C the nonraft phase becomes the continuous phase with
      isolated domains of the raft phase dispersed in it.

PMID- 16407161
TI  - Role of Src in C3 transient receptor potential channel function and evidence for
      a heterogeneous makeup of receptor- and store-operated Ca2+ entry channels.
AB  - Receptor-operated Ca2+ entry (ROCE) and store-operated Ca2+ entry (SOCE) are
      known to be inhibited by tyrosine kinase inhibitors and activation of C-type
      transient receptor potential channel (TRPC) isoform 3 (TRPC3), a cation channel
      thought to be involved in SOCE and/or ROCE, was recently shown to depend on src
      tyrosine kinase activity. What is not known is the step at which src acts on
      TRPC3 and whether the role for tyrosine kinases in ROCE or SOCE is a general
      phenomenon. Using in vitro and in cell protein-protein interaction assays we now
      report that src phosphorylates TRPC3 at Y226 and that formation of phospho-Y226
      is essential for TRPC3 activation. This requirement is unique for TRPC3 because
      (i) mutation of the cognate tyrosines of the closely related TRPC6 and TRPC7 had
      no effect; (ii) TRPC6 and TRPC7 were activated in src-, yes-, and fyn-deficient
      cells; and (iii) src, but not yes or fyn, rescued TRPC3 activation in src-, yes-,
      and fyn-deficient cells. The Src homology 2 domain of src was found to interact
      with either the N or the C termini of all TRPCs, suggesting that other tyrosine
      kinases may play a role in ion fluxes mediated by TRPCs other than TRPC3. A side
      by-side comparison of the effects of genistein (a general tyrosine kinase
      inhibitor) on endogenous ROCE and SOCE in mouse fibroblasts, HEK and COS-7 cells,
      and ROCE in HEK cells mediated by TRPC3, TRPC6, TRPC7, and TRPC5 showed
      differences that argue for ROCE and SOCE channels to be heterogeneous.

PMID- 16407162
TI  - The activity of a human endoplasmic reticulum-associated degradation E3, gp78,
      requires its Cue domain, RING finger, and an E2-binding site.
AB  - Efficient targeting of proteins for degradation from the secretory pathway is
      essential to homeostasis. This occurs through endoplasmic reticulum (ER)
      associated degradation (ERAD). In this study, we establish that a human ubiquitin
      ligase (E3), gp78, and a specific E2, Ube2g2, are both critically important for
      ERAD of multiple substrates. gp78 exhibits a complex domain structure that, in
      addition to the RING finger, includes a ubiquitin-binding Cue domain and a
      specific binding site for Ube2g2. Disruption of either of these domains abolishes
      gp78-mediated ubiquitylation and protein degradation, resulting in accumulation
      of substrates in their fully glycosylated forms in the ER. This suggests that
      gp78-mediated ubiquitylation is an early step in ERAD that precedes dislocation
      of substrates from the ER. The in vivo requirement for both an E2-binding site
      distinct from the RING finger and a ubiquitin-binding domain intrinsic to an E3
      suggests a previously unappreciated level of complexity in ubiquitin ligase
      function. These results also provide proof of principle that interrupting a
      specific E2-E3 interaction can selectively inhibit ERAD.

PMID- 16407163
TI  - A nucleoporin is required for induction of Ca2+ spiking in legume nodule
      development and essential for rhizobial and fungal symbiosis.
AB  - Nuclear-cytoplasmic partitioning and traffic between cytoplasmic and nuclear
      compartments are fundamental processes in eukaryotic cells. Nuclear pore
      complexes mediate transport of proteins, RNAs and ribonucleoprotein particles in
      and out of the nucleus. Here we present positional cloning of a plant nucleoporin
      gene, Nup133, essential for a symbiotic signal transduction pathway shared by
      Rhizobium bacteria and mycorrhizal fungi. Mutation of Nup133 results in a
      temperature sensitive nodulation deficient phenotype and absence of mycorrhizal
      colonization. Root nodules developing with reduced frequency at permissive
      temperatures are ineffective and electron microscopy show that Rhizobium bacteria
      are not released from infection threads. Measurement of ion fluxes using a
      calcium-sensitive dye show that Nup133 is required for the Ca2+ spiking normally
      detectable within minutes after application of purified rhizobial Nod-factor
      signal molecules to root hairs. Localization of NUP133 in the nuclear envelope of
      root cells and root hair cells shown with enhanced yellow fluorescent protein
      fusion proteins suggests a novel role for NUP133 nucleoporins in a rapid nuclear
      cytoplasmic communication after host-plant recognition of symbiotic microbes. Our
      results identify a component of an intriguing signal process requiring
      interaction at the cell plasma membrane and at intracellular nuclear and plastid
      organelle-membranes to induce a second messenger.

PMID- 16407164
TI  - Stable isotopes in elephant hair document migration patterns and diet changes.
AB  - We use chronologies of stable isotopes measured from elephant (Loxodonta
      africana) hair to determine migration patterns and seasonal diet changes in
      elephants in and near Samburu National Reserve in northern Kenya. Stable carbon
      isotopes record diet changes, principally enabling differentiation between browse
      and tropical grasses, which use the C3 and C4 photosynthetic pathways,
      respectively; stable nitrogen isotopes record regional patterns related to
      aridity, offering insight into localized ranging behavior. Isotopically
      identified range shifts were corroborated by global positioning system radio
      tracking data of the studied individuals. Comparison of the stable isotope record
      in the hair of one migrant individual with that of a resident population shows
      important differences in feeding and ranging behavior over time. Our analysis
      indicates that differences are the result of excursions into mesic environments
      coupled with intermittent crop raiding by the migrant individual. Variation in
      diet, quantified by using stable isotopes, can offer insight into diet-related
      wildlife behavior.

PMID- 16407165
TI  - Essential genes of a minimal bacterium.
AB  - Mycoplasma genitalium has the smallest genome of any organism that can be grown
      in pure culture. It has a minimal metabolism and little genomic redundancy.
      Consequently, its genome is expected to be a close approximation to the minimal
      set of genes needed to sustain bacterial life. Using global transposon
      mutagenesis, we isolated and characterized gene disruption mutants for 100
      different nonessential protein-coding genes. None of the 43 RNA-coding genes were
      disrupted. Herein, we identify 382 of the 482 M. genitalium protein-coding genes
      as essential, plus five sets of disrupted genes that encode proteins with
      potentially redundant essential functions, such as phosphate transport. Genes
      encoding proteins of unknown function constitute 28% of the essential protein
      coding genes set. Disruption of some genes accelerated M. genitalium growth.

PMID- 16407166
TI  - Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter
      activity by the activation of PPARgamma.
AB  - Epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs
      (NSAIDs) decrease the risk for Alzheimer's disease (AD). Certain NSAIDs can
      activate the peroxisome proliferator-activated receptor-gamma (PPARgamma), which
      is a nuclear transcriptional regulator. Here we show that PPARgamma depletion
      potentiates beta-secretase [beta-site amyloid precursor protein cleaving enzyme
      (BACE1)] mRNA levels by increasing BACE1 gene promoter activity. Conversely,
      overexpression of PPARgamma, as well as NSAIDs and PPARgamma activators, reduced
      BACE1 gene promoter activity. These results suggested that PPARgamma could be a
      repressor of BACE1. We then identified a PPARgamma responsive element (PPRE) in
      the BACE1 gene promoter. Mutagenesis of the PPRE abolished the binding of
      PPARgamma to the PPRE and increased BACE1 gene promoter activity. Furthermore,
      proinflammatory cytokines decreased PPARgamma gene transcription, and this effect
      was supressed by NSAIDs. We also demonstrate that in vivo treatment with
      PPARgamma agonists increased PPARgamma and reduced BACE1 mRNA and intracellular
      beta-amyloid levels. Interestingly, brain extracts from AD patients showed
      decreased PPARgamma expression and binding to PPRE in the BACE1 gene promoter.
      Our data strongly support a major role of PPARgamma in the modulation of amyloid
      beta generation by inflammation and suggest that the protective mechanism of
      NSAIDs in AD involves activation of PPARgamma and decreased BACE1 gene
      transcription.

PMID- 16407167
TI  - Top-down facilitation of visual recognition.
AB  - Cortical analysis related to visual object recognition is traditionally thought
      to propagate serially along a bottom-up hierarchy of ventral areas. Recent
      proposals gradually promote the role of top-down processing in recognition, but
      how such facilitation is triggered remains a puzzle. We tested a specific model,
      proposing that low spatial frequencies facilitate visual object recognition by
      initiating top-down processes projected from orbitofrontal to visual cortex. The
      present study combined magnetoencephalography, which has superior temporal
      resolution, functional magnetic resonance imaging, and a behavioral task that
      yields successful recognition with stimulus repetitions. Object recognition
      elicited differential activity that developed in the left orbitofrontal cortex 50
      ms earlier than it did in recognition-related areas in the temporal cortex. This
      early orbitofrontal activity was directly modulated by the presence of low
      spatial frequencies in the image. Taken together, the dynamics we revealed
      provide strong support for the proposal of how top-down facilitation of object
      recognition is initiated, and our observations are used to derive predictions for
      future research.

PMID- 16407168
TI  - PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired
      upon macrophage differentiation from a monocyte.
AB  - Monocyte-to-macrophage differentiation with the cytokine granulocyte-macrophage
      colony-stimulating factor induces expression of the cyclic nucleotide
      phosphodiesterase PDE1B2. However, what role PDE1B2 plays in macrophage biology
      has not been elucidated. We have addressed this question by inhibiting PDE1B2
      induction by using RNA interference. Using a retrovirus-based system, we created
      HL-60 stable cell lines that express a short-hairpin RNA targeting PDE1B2. HL-60
      cells treated with phorbol-12-myristate-13-acetate differentiate to a macrophage
      like phenotype and up-regulate PDE1B2. However, expression of PDE1B2 short
      hairpin RNA effectively suppresses PDE1B2 mRNA, protein, and activity up
      regulation. Using the HL-60 PDE1B2 knockdown cells and agonists for either
      adenylyl or guanylyl cyclase, it was found that PDE1B2 predominantly regulates
      cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists.
      Furthermore, in intact HL-60 cells, PDE1B2 activity can be regulated by changes
      in Ca+2 levels. Inhibiting PDE1B2 up-regulation does not prevent HL-60 cell
      differentiation, because several markers of macrophage differentiation are
      unaffected. However, suppression of PDE1B2 expression alters some aspects of the
      macrophage-like phenotype, because cell spreading, phagocytic ability, and CD11b
      expression are augmented. The cAMP analog 8-Bromo-cAMP reverses the changes
      caused by PDE1B2 knockdown. Also, PDE1B2 knockdown cells have lower basal levels
      of cAMP and alterations in the phosphorylation state of several probable PKA
      substrate proteins. Thus, the effects of PDE1B2 on differentiation may ultimately
      be mediated through decreased cAMP. In conclusion, PDE1B2 regulates a subset of
      phenotypic changes that occur upon phorbol-12-myristate-13-acetate-induced
      differentiation and likely also plays a role in differentiated macrophages by
      regulating agonist-stimulated cGMP levels.

PMID- 16407169
TI  - RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid
      induced tolerance associated with hyperalgesia.
AB  - Neuropeptide FF (NPFF) has been proposed to play a role in pain modulation,
      opioid tolerance, and several other physiological processes. However,
      pharmacological agents that would help define physiological roles for this
      peptide are still missing. Here we report the discovery of a potent and selective
      NPFF receptor antagonist, RF9, that can be administered systemically. This
      compound does not show any effects by itself but can block efficiently the
      increase in blood pressure and heart rate evoked by NPFF. When chronically
      coinjected with heroin, RF9 completely blocks the delayed and long-lasting
      paradoxical opioid-induced hyperalgesia and prevents the development of
      associated tolerance. Our data indicate that NPFF receptors are part of a bona
      fide antiopioid system and that selective antagonists of these receptors could
      represent useful therapeutic agents for improving the efficacy of opioids in
      chronic pain treatment.

PMID- 16407170
TI  - Identification of the mobile light-harvesting complex II polypeptides for state
      transitions in Chlamydomonas reinhardtii.
AB  - State transition in photosynthesis is a short-term balancing mechanism of energy
      distribution between photosystem I (PSI) and photosystem II (PSII). When PSII is
      preferentially excited (state 2), a pool of mobile light-harvesting complex II
      (LHCII) antenna proteins is thought to migrate from PSII to PSI, but biochemical
      evidence for a physical association between LHCII proteins and PSI in state 2 is
      weak. Here, using the green alga Chlamydomonas reinhardtii, which has a high
      capacity for state transitions, we report the isolation of PSI-light-harvesting
      complex I (LHCI) super-complexes from cells locked into state 1 and state 2. We
      solubilized the thylakoid membranes with a mild detergent, separated the proteins
      by sucrose density gradient centrifugation, and subjected gradient fractions to
      gel-filtration chromatography. Three LHCII polypeptides were associated with a
      PSI-LHCI supercomplex only in state 2; we identified them as two minor monomeric
      LHCII proteins (CP26 and CP29) and one previously unreported major LHCII protein
      type II, or LhcbM5. These three LHCII proteins, in addition to the major trimeric
      LHCII proteins, were phosphorylated upon transition to state 2. The corresponding
      phylogenetic tree indicates that among the LHCII proteins associated with PSII,
      these three LHCII proteins are the most similar to the LHC proteins for PSI
      (LHCI). Our results are important because CP26, CP29, and LhcbM5, which have been
      viewed as belonging solely to the PSII complex, are now postulated to shuttle
      between PSI and PSII during state transitions, thereby acting as docking sites
      for the trimeric LHCII proteins in both PSI and PSII.

PMID- 16407171
TI  - Membrane-associated STAT3 and PY-STAT3 in the cytoplasm.
AB  - Signal transduction from the plasma membrane to the nucleus by STAT proteins is
      widely represented as exclusively a soluble cytosolic process. Using cell
      fractionation methods, we observed that approximately 5% of cytoplasmic STAT3 was
      constitutively associated with the purified early endosome (EE) fraction in human
      Hep3B liver cells. By 15-30 min after interleukin-6 (IL-6) treatment, up to two
      thirds of cytoplasmic Tyr-phosphorylated STAT3 can be associated with the
      purified early endosome fraction (Rab-5-, EEA1-, transferrin receptor-, and
      clathrin-positive fraction). Electron microscopy, immunofluorescence, and
      detergent dissection approaches confirmed the association of STAT3 and PY-STAT3
      with early endosomes. STAT3 was constitutively associated with clathrin heavy
      chain in membrane and in the 1- to 2-MDa cytosolic complexes. The membrane
      association was dynamic in that, within 15 min of treatment with the vicinal
      thiol cross-linker phenylarsine oxide, there was a dramatic increase in bulk
      STAT3 association with sedimentable membranes. The functional contribution of PY
      STAT3 association with the endocytic pathway was evaluated in transient
      transfection assays using IL-6-inducible STAT3-reporter-luciferase constructs and
      selective regulators of this pathway. STAT3-transcriptional activation was
      inhibited by expression constructs for dominant negative dynamin K44A, epsin 2a,
      amphiphysin A1, and clathrin light chain but enhanced by that for the active
      dynamin species MxA. Taken together, these studies emphasize the contribution of
      the endocytic pathway to productive IL-6/STAT3 signaling.

PMID- 16407172
TI  - Structural regions of MD-2 that determine the agonist-antagonist activity of
      lipid IVa.
AB  - A cell surface receptor complex consisting of CD14, Toll-like receptor (TLR4),
      and MD-2 recognizes lipid A, the active moiety of lipopolysaccharide (LPS).
      Escherichia coli-type lipid A, a typical lipid A molecule, potently activates
      both human and mouse macrophage cells, whereas the lipid A precursor, lipid IVa,
      activates mouse macrophages but is inactive and acts as an LPS antagonist in
      human macrophages. This animal species-specific activity of lipid IVa involves
      the species differences in MD-2 structure. We explored the structural region of
      MD-2 that determines the agonistic and antagonistic activities of lipid IVa to
      induce nuclear factor-kappaB activation. By expressing human/mouse chimeric MD-2
      together with mouse CD14 and TLR4 in human embryonic kidney 293 cells, we found
      that amino acid regions 57-79 and 108-135 of MD-2 determine the species-specific
      activity of lipid IVa. We also showed that the replacement of Thr(57), Val(61),
      and Glu(122) of mouse MD-2 with corresponding human MD-2 sequence or alanines
      impaired the agonistic activity of lipid IVa, and antagonistic activity became
      evident. These mutations did not affect the activation of nuclear factor-kappaB,
      TLR4 oligomerization, and inducible phosphorylation of IkappaBalpha in response
      to E. coli-type lipid A. These results indicate that amino acid residues 57, 61,
      and 122 of mouse MD-2 are critical to determine the agonist-antagonist activity
      of lipid IVa and suggest that these amino acid residues may be involved in the
      discrimination of lipid A structure.

PMID- 16407173
TI  - Overexpression of cytosolic group IVA phospholipase A2 protects cells from Ca2+
      dependent death.
AB  - The calcium ionophore ionomycin induces apoptosis-like events in the human
      embryonic kidney cell line at early times. Plasma membrane blebbing,
      mitochondrial depolarization, externalization of phosphatidylserine, and nuclear
      permeability changes can all be observed within 15 min of treatment. However,
      there is no activation of caspases or chromatin condensation. Expression of a
      fusion protein containing the enhanced green fluorescent protein (EGFP) and human
      cytosolic Group IVA phospholipase A(2)alpha (EGFP-cPLA(2)alpha) in these cells
      prevents ionomycin-induced phosphatidylserine externalization and death. Cells
      expressing the cPLA(2)alpha mutant D43N, which does not bind calcium, retain
      their susceptibility to ionomycin-induced cell death. Both nonexpressing and EGFP
      D43N-cPLA(2)alpha-expressing human embryonic kidney cells can be spared from
      ionomycin-induced cell death by pretreating them with exogenous arachidonic acid.
      Moreover, during calcium overload, mitochondrial depolarization is significantly
      lower in the EGFP-cPLA(2)alpha-expressing cells than in cells expressing normal
      amounts of cPLA(2)alpha. These results suggest that early cell death events
      promoted by an overload of calcium can be prevented by the presence of high
      levels of arachidonic acid.

PMID- 16407174
TI  - Solution structure of the immunodominant domain of protective antigen GNA1870 of
      Neisseria meningitidis.
AB  - GNA1870, a 28-kDa surface-exposed lipoprotein of Neisseria meningitidis recently
      discovered by reverse vaccinology, is one of the most potent antigens of
      Meningococcus and a promising candidate for a universal vaccine against a
      devastating disease. Previous studies of epitope mapping and genetic
      characterization identified residues critical for bactericidal response within
      the C-terminal domain of the molecule. To elucidate the conformation of
      protective epitopes, we used NMR spectroscopy to obtain the solution structure of
      the immunodominant 18-kDa C-terminal portion of GNA1870. The structure consists
      of an eight-stranded antiparallel beta-barrel overlaid by a short alpha-helix
      with an unstructured N-terminal end. Residues previously shown to be important
      for antibody recognition were mapped on loops facing the same ridge of the
      molecule. The sequence similarity of GNA1870 with members of the bacterial
      transferrin receptor family allows one to predict the folding of this class of
      well known bacterial antigens, providing the basis for the rational engineering
      of high affinity B cell epitopes.

PMID- 16407175
TI  - Consequences of N-acylation on structure and membrane binding properties of
      dermaseptin derivative K4-S4-(1-13).
AB  - Acyl conjugation to antimicrobial peptides is known to enhance antimicrobial
      properties. Here, we investigated the consequences of aminolauryl (NC(12))
      conjugation to the dermaseptin derivative K(4)-S4-(1-13) (P) on binding
      properties to bilayer models mimicking bacterial plasma membrane, which is often
      cited as the ultimate site of action. Isothermal titration calorimetry revealed
      that acylation was responsible for enhancing the binding affinity of NC(12)-P
      compared with P (K = 13 x 10(5) and 1.5 x 10(5) m(-1), respectively). Surface
      plasmon resonance measurements confirmed the isothermal titration calorimetry
      results (K(app) = 12.6 x 10(5) and 1.53 x 10(5) m(-1), respectively) and further
      indicated that enhanced adhesion affinity (K(adhesion) = 3 x 10(5) and 1 x 10(5)
      m(-1), respectively) was coupled to enhanced tendency to insert within the
      bilayer (K(insertion) = 4.5 and 1.5, respectively). To gain insight into the
      molecular basis for these observations, we investigated the three-dimensional
      structures in the presence of dodecylphosphocholine using NMR. The ensemble of
      NMR-calculated structures (backbone root mean square deviation <0.6 A) showed
      that the acyl moiety was responsible for a significant molecular reorganization,
      possibly affecting the electrostatic potential distribution in NC(12)-P relative
      to that of P. The combined data present compelling evidence in support of the
      hypothesis that N-acylation affects antimicrobial properties by modifying the
      secondary structure of the peptide in a manner that facilitates contact with the
      membrane and consequently increases its disruption.

PMID- 16407176
TI  - The Zn2+-transporting pathways in pancreatic beta-cells: a role for the L-type
      voltage-gated Ca2+ channel.
AB  - In pancreatic beta-cells Zn(2+) is crucial for insulin biosynthesis and
      exocytosis. Despite this, little is known about mechanisms of Zn(2+) transport
      into beta-cells or the regulation and compartmentalization of Zn(2+) within this
      cell type. Evidence suggests that Zn(2+) in part enters neurons and myocytes
      through specific voltage-gated calcium channels (VGCC). Using a Zn(2+)-selective
      fluorescent dye with high affinity and quantum yield, FluoZin-3 AM and the plasma
      membrane potential dye DiBAC(4)(3) we applied fluorescent microscopy techniques
      for analysis of Zn(2+)-accumulating pathways in mouse islets, dispersed islet
      cells, and beta-cell lines (MIN6 and beta-TC6f7 cells). Because the stimulation
      of insulin secretion is associated with cell depolarization, Zn(2+) (5-10 mum)
      uptake was analyzed under basal (1 mm glucose) and stimulatory (10-20 mm glucose,
      tolbutamide, tetraethylammonium, and high K(+)) conditions. Under both basal and
      depolarized states, beta-cells were capable of Zn(2+) uptake, and switching from
      basal to depolarizing conditions resulted in a marked increase in the rate of
      Zn(2+) accumulation. Importantly, L-type VGCC (L-VGCC) blockers (verapamil,
      nitrendipine, and nifedipine) as well as nonspecific inhibitors of Ca(2+)
      channels, Gd(3+) and La(3+), inhibited Zn(2+) uptake in beta-cells under
      stimulatory conditions with little or no change in Zn(2+) accumulation under low
      glucose conditions. To determine the mechanism of VGCC-independent Zn(2+) uptake
      the expression of a number of ZIP family Zn(2+) transporter mRNAs in islets and
      beta-cells was investigated. In conclusion, we demonstrate for the first time
      that, in part, Zn(2+) transport into beta-cells takes place through the L-VGCC.
      Our investigation demonstrates direct Zn(2+) accumulation in insulin-secreting
      cells by two pathways and suggests that the rate of Zn(2+) transport across the
      plasma membrane is dependent upon the metabolic status of the cell.

PMID- 16407177
TI  - Type I collagen abrogates the clathrin-mediated internalization of membrane type
      1 matrix metalloproteinase (MT1-MMP) via the MT1-MMP hemopexin domain.
AB  - Type I collagen (Col I)-stimulated matrix metalloproteinase-2 (MMP-2) activation
      via membrane type 1 MMP (MT1-MMP) involves both a transcriptional increase in MT1
      MMP expression and a nontranscriptional response mediated by preexisting MT1-MMP.
      In order to identify which MT1-MMP domains were required for the
      nontranscriptional response, MCF-7 cells that lack endogenous MT1-MMP were
      transfected with either wild type or domain mutant MT1-MMP constructs. We
      observed that mutant constructs lacking the MT1-MMP cytoplasmic tail were able to
      activate MMP-2 in response to Col I but not a construct lacking the MT1-MMP
      hemopexin domain. Col I did not alter total MT1-MMP protein levels; nor did it
      appear to directly induce MT1-MMP oligomerization. Col I did, however,
      redistribute preexisting MT1-MMP to the cell periphery compared with unstimulated
      cells that displayed a more diffuse staining pattern. In addition, Col I blocked
      the internalization of MT1-MMP in a dynamin-dependent manner via clathrin-coated
      pit-mediated endocytosis. This mechanism of impaired internalization is different
      from that reported for concanavalin A, since it is not mediated by the
      cytoplasmic tail of MT1-MMP but rather by the hemopexin domain. In summary, upon
      Col I binding to its cell surface receptor, MT1-MMP internalization via clathrin
      coated pit-mediated endocytosis is impaired through interactions with the
      hemopexin domain, thereby regulating its function and ability to activate MMP-2.

PMID- 16407178
TI  - Fibrillins 1 and 2 perform partially overlapping functions during aortic
      development.
AB  - Fibrillin-rich microfibrils are extracellular assemblies that impart structural
      properties to the connective tissue. To elucidate the contribution of fibrillin
      rich microfibrils to organogenesis, we have examined the vascular phenotype of a
      newly created strain of mice that completely lacks fibrillin-1 and the
      consequences of combined deficiency of fibrillins 1 and 2 on tissue formation.
      The results demonstrated that fibrillins 1 and 2 perform partially overlapping
      functions during aortic development. Fbn1-/- mice died soon after birth from
      ruptured aortic aneurysm, impaired pulmonary function, and/or diaphragmatic
      collapse. Analysis of the neonatal Fbn1-/- aorta documented a disorganized and
      poorly developed medial layer but normal levels of elastin cross-links.
      Transcriptional profiling revealed that aneurysm progression in Fbn1 null mice is
      accompanied by unproductive up-regulation of gene products normally involved in
      tissue repair and vascular integrity, such as plasminogen activator inhibitor-1,
      activin A, and cysteine-rich angiogenic protein 61. In contrast to Fbn1-/- mice,
      Fbn2 null mice had a well developed and morphologically normal aortic wall.
      However, virtually all Fbn1-/-;Fbn2-/- embryos and about half of the Fbn1+/-;Fbn2
      /- embryos died in utero and displayed a significantly more severe vascular
      phenotype than Fbn1-/- mice. Consistent with a specialized function of fibrillin
      2, electron microscopy visualized ultrastructurally different microfibrils in
      Fbn1 null compared with control cell cultures. Collectively, these data
      demonstrate that involvement of fibrillin-2 in the initial assembly of the aortic
      matrix overlaps in part with fibrillin-1 and that continued fibrillin-1
      deposition is absolutely required for the maturation and function of the vessel
      during neonatal life.

PMID- 16407179
TI  - Mutation of a conserved threonine in the third transmembrane helix of alpha- and
      beta-connexins creates a dominant-negative closed gap junction channel.
AB  - Single site mutations in connexins have provided insights about the influence
      specific amino acids have on gap junction synthesis, assembly, trafficking, and
      functionality. We have discovered a single point mutation that eliminates
      functionality without interfering with gap junction formation. The mutation
      occurs at a threonine residue located near the cytoplasmic end of the third
      transmembrane helix. This threonine is strictly conserved among members of the
      alpha- and beta-connexin subgroups but not the gamma-subgroup. In HeLa cells,
      connexin43 and connexin26 mutants are synthesized, traffic to the plasma
      membrane, and make gap junctions with the same overall appearance as wild type.
      We have isolated connexin26T135A gap junctions both from HeLa cells and
      baculovirus-infected insect Sf9 cells. By using cryoelectron microscopy and
      correlation averaging, difference images revealed a small but significant size
      change within the pore region and a slight rearrangement of the subunits between
      mutant and wild-type connexons expressed in Sf9 cells. Purified, detergent
      solubilized mutant connexons contain both hexameric and partially disassembled
      structures, although wild-type connexons are almost all hexameric, suggesting
      that the three-dimensional mutant connexon is unstable. Mammalian cells
      expressing gap junction plaques composed of either connexin43T154A or
      connexin26T135A showed an absence of dye coupling. When expressed in Xenopus
      oocytes, these mutants, as well as a cysteine substitution mutant of connexin50
      (connexin50T157C), failed to produce electrical coupling in homotypic and
      heteromeric pairings with wild type in a dominant-negative effect. This mutant
      may be useful as a tool for knocking down or knocking out connexin function in
      vitro or in vivo.

PMID- 16407180
TI  - Docking studies show that D-glucose and quercetin slide through the transporter
      GLUT1.
AB  - On a three-dimensional templated model of GLUT1 (Protein Data Bank code 1SUK), a
      molecular recognition program, AUTODOCK 3, reveals nine hexose-binding clusters
      spanning the entire "hydrophilic" channel. Five of these cluster sites are within
      3-5 A of 10 glucose transporter deficiency syndrome missense mutations. Another
      three sites are within 8 A of two other missense mutations. D-glucose binds to
      five sites in the external channel opening, with increasing affinity toward the
      pore center and then passes via a narrow channel into an internal vestibule
      containing four lower affinity sites. An external site, not adjacent to any
      mutation, also binding phloretin but recognizing neither D-fructose nor L
      glucose, may be the main threading site for glucose uptake. Glucose exit from
      human erythrocytes is inhibited by quercetin (K(i) = 2.4 mum) but not anionic
      quercetin-semiquinone. Quercetin influx is retarded by extracellular D-glucose
      (50 mm) but not by phloretin and accelerated by intracellular D-glucose.
      Quercetin docking sites are absent from the external opening but fill the entire
      pore center. In the inner vestibule, Glu(254) and Lys(256) hydrogen-bond
      quercetin (K(i) approximately 10 microm) but not quercetin-semiquinone.
      Consistent with the kinetics, this site also binds D-glucose, so quercetin
      displacement by glucose could accelerate quercetin influx, whereas quercetin
      binding here will competitively inhibit glucose efflux. Beta-D-hexoses dock twice
      as frequently as their alpha-anomers to the 23 aromatic residues in the transport
      pathway, suggesting that endocyclic hexose hydrogens, as with maltosaccharides in
      maltoporins, form pi-bonds with aromatic rings and slide between sites instead of
      being translocated via a single alternating site.

PMID- 16407181
TI  - Virus-host interaction minireview series: human immunodeficiency virus, hepatitis
      C virus, and influenza virus.

PMID- 16407182
TI  - From structure to function: new insights into hepatitis C virus RNA replication.

PMID- 16407183
TI  - APOBEC3 cytidine deaminases: distinct antiviral actions along the retroviral life
      cycle.
AB  - The field of human immunodeficiency virus (HIV) biology has been galvanized by
      the discovery of innate APOBEC3 cytidine deaminases, which pose powerful barriers
      to the replication of HIV and other retroviruses. Rapid progress has been made in
      defining their action, intriguing regulation within cells, expanded range of
      retroviral targets, and counterstrikes utilized by retroviruses against them.
      Although scientifically fascinating, advances in APOBEC3 biology may lead to new
      antiviral drugs and improved lentiviral vectors for gene therapy.

PMID- 16407184
TI  - The M2 proton channels of influenza A and B viruses.

PMID- 16407185
TI  - Efficient twin arginine translocation (Tat) pathway transport of a precursor
      protein covalently anchored to its initial cpTatC binding site.
AB  - The thylakoid twin arginine protein translocation (Tat) system operates by a
      cyclical mechanism in which precursors bind to a cpTatC-Hcf106 receptor complex,
      which then recruits Tha4 to form the translocase. After translocation, the
      translocase disassembles. Here, we fine-mapped initial interactions between
      precursors and the components of the receptor complex. Precursors with (Tmd)Phe
      substitutions in the signal peptide and early mature domain were bound to
      thylakoids and photo-cross-linked to components. cpTatC and Hcf106 were found to
      interact with different regions of the signal peptide. cpTatC cross-linked
      strongly to residues in the immediate vicinity of the twin arginine motif. Hcf106
      cross-linked less strongly to residues in the hydrophobic core and the early
      mature domain. To determine whether precursors must leave their initial sites of
      interaction during translocation, cross-linked precursors were subjected to
      protein transport conditions. tOE17 cross-linked to cpTatC was efficiently
      translocated, indicating that the mature domain of the precursor can be
      translocated while the signal peptide remains anchored to the receptor complex.

PMID- 16407186
TI  - Oligomers of Tha4 organize at the thylakoid Tat translocase during protein
      transport.
AB  - The Tat (twin arginine translocation) systems of thylakoids and bacteria
      transport fully folded protein substrates without breaching the permeability
      barrier of the membrane. Two components of the thylakoid system, cpTatC and
      Hcf106, compose a precursor-bound receptor complex. The third component, Tha4,
      assembles with the precursor-bound receptor complex for the translocation step
      and is thought to compose at least part of the protein-conducting channel. Here,
      we used two different cross-linking approaches to explore the organization of
      Tha4 in the translocase. These cross-linking techniques showed that transition to
      an active protein transport state resulted in an alignment of the Tha4
      amphipathic helix and C-terminal tail domains to form Tha4 oligomers.
      Oligomerization required functional Tha4, a twin arginine signal peptide, and an
      active cpTatC-Hcf106 receptor complex. The spectrum of oligomers obtained was
      independent of the mature folded domain of the precursor. We propose a trapdoor
      mechanism for translocation whereby aligned oligomers of Tha4 amphipathic helices
      fold into the membrane to allow formfitting passage of precursor proteins.

PMID- 16407187
TI  - Cholesterol-regulated translocation of NPC1L1 to the cell surface facilitates
      free cholesterol uptake.
AB  - Although NPC1L1 is required for intestinal cholesterol absorption, data
      demonstrating mechanisms by which this protein facilitates the process are few.
      In this study, a hepatoma cell line stably expressing human NPC1L1 was
      established, and cholesterol uptake was studied. A relationship between NPC1L1
      intracellular trafficking and cholesterol uptake was apparent. At steady state,
      NPC1L1 proteins localized predominantly to the transferrin-positive endocytic
      recycling compartment, where free cholesterol also accumulated as revealed by
      filipin staining. Interestingly, acute cholesterol depletion induced with methyl
      beta-cyclodextrin stimulated relocation of NPC1L1 to the plasma membrane,
      preferentially to a newly formed "apical-like" subdomain. This translocation was
      associated with a remarkable increase in cellular cholesterol uptake, which in
      turn was dose-dependently inhibited by ezetimibe, a novel cholesterol absorption
      inhibitor that specifically binds to NPC1L1. These findings define a cholesterol
      regulated endocytic recycling of NPC1L1 as a novel mechanism regulating cellular
      cholesterol uptake.

PMID- 16407188
TI  - Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen
      species and differential regulation of p38 kinase isoforms.
AB  - From human and animal studies, estrogen is known to protect the myocardium from
      an ischemic insult. However, there is limited knowledge regarding mechanisms by
      which estrogen directly protects cardiomyocytes. In this report, we employed an
      in vitro model, in which cultured rat cardiomyocytes underwent prolonged hypoxia
      followed by reoxygenation (H/R), to study the cardioprotective mechanism of
      estrogen. 17-beta-estradiol (E2) acting via estrogen receptors inhibited H/R
      induced apoptosis of cardiomyocytes. Mitochondrial reactive oxygen species (ROS)
      generated from H/R activated p38alpha MAPK, and inhibition of p38alpha with
      SB203580 significantly prevented H/R-induced cell death. E2 suppressed ROS
      formation and p38alpha activation by H/R and concomitantly augmented the activity
      of p38beta. Unlike p38alpha, p38beta was little affected by H/R. Dominant
      negative p38beta protein expression decreased E2-mediated cardiomyocyte survival
      and ROS suppression during H/R stress. The prosurvival signaling molecule,
      phosphoinositol-3 kinase (PI3K), has previously been linked to cell survival
      following ischemia-reperfusion injury. Here, E2-activated PI3K was found to
      inhibit ROS generated from H/R injury, leading to inhibition of downstream
      p38alpha. We further linked these signaling pathways in that p38beta was
      activated by E2 stimulation of PI3K. Thus, E2 differentially modulated two major
      isoforms of p38, leading to cardiomyocyte survival. This was achieved by
      signaling through PI3K, integrating cell survival mediators.

PMID- 16407189
TI  - Nuclear transportation of diacylglycerol kinase gamma and its possible function
      in the nucleus.
AB  - Diacylglycerol kinases (DGKs) convert diacylglycerol (DG) to phosphatidic acid,
      and both lipids are known to play important roles in lipid signal transduction.
      Thereby, DGKs are considered to be a one of the key players in lipid signaling,
      but its physiological function remains to be solved. In an effort to investigate
      one of nine subtypes, we found that DGKgamma came to be localized in the nucleus
      with time in all cell lines tested while seen only in the cytoplasm at the early
      stage of culture, indicating that DGKgamma is transported from the cytoplasm to
      the nucleus. The nuclear transportation of DGKgamma didn't necessarily need DGK
      activity, but its C1 domain was indispensable, suggesting that the C1 domain of
      DGKgamma acts as a nuclear transport signal. Furthermore, to address the function
      of DGKgamma in the nucleus, we produced stable cell lines of wild-type DGKgamma
      and mutants, including kinase negative, and investigated their cell size, growth
      rate, and cell cycle. The cells expressing the kinase-negative mutant of DGKgamma
      were larger in size and showed slower growth rate, and the S phase of the cells
      was extended. These findings implicate that nuclear DGKgamma regulates cell
      cycle.

PMID- 16407190
TI  - Sodium and epithelial sodium channels participate in the regulation of the
      capacitation-associated hyperpolarization in mouse sperm.
AB  - In a process called capacitation, mammalian sperm gain the ability to fertilize
      after residing in the female tract. During capacitation the mouse sperm plasma
      membrane potential (E(m)) hyperpolarizes. However, the mechanisms that regulate
      sperm E(m) are not well understood. Here we show that sperm hyperpolarize when
      external Na(+) is replaced by N-methyl-glucamine. Readdition of external Na(+)
      restores a more depolarized E(m) by a process that is inhibited by amiloride or
      by its more potent derivative 5-(N-ethyl-N-isopropyl)-amiloride hydrochloride.
      These findings indicate that under resting conditions an electrogenic Na(+)
      transporter, possibly involving an amiloride sensitive Na(+) channel, may
      contribute to the sperm resting E(m). Consistent with this proposal, patch clamp
      recordings from spermatogenic cells reveal an amiloride-sensitive inward Na(+)
      current whose characteristics match those of the epithelial Na(+) channel (ENaC)
      family of epithelial Na(+) channels. Indeed, ENaC-alpha and -delta mRNAs were
      detected by reverse transcription-PCR in extracts of isolated elongated
      spermatids, and ENaC-alpha and -delta proteins were found on immunoblots of sperm
      membrane preparations. Immunostaining indicated localization of ENaC-alpha to the
      flagellar midpiece and of ENaC-delta to the acrosome. Incubations known to
      produce capacitation in vitro or induction of capacitation by cell-permeant cAMP
      analogs decreased the depolarizing response to the addition of external Na(+).
      These results suggest that increases in cAMP content occurring during
      capacitation may inhibit ENaCs to produce a required hyperpolarization of the
      sperm membrane.

PMID- 16407191
TI  - Structural and computational analysis of the quinone-binding site of complex II
      (succinate-ubiquinone oxidoreductase): a mechanism of electron transfer and
      proton conduction during ubiquinone reduction.
AB  - The transfer of electrons and protons between membrane-bound respiratory
      complexes is facilitated by lipid-soluble redox-active quinone molecules (Q).
      This work presents a structural analysis of the quinone-binding site (Q-site)
      identified in succinate:ubiquinone oxidoreductase (SQR) from Escherichia coli.
      SQR, often referred to as Complex II or succinate dehydrogenase, is a functional
      member of the Krebs cycle and the aerobic respiratory chain and couples the
      oxidation of succinate to fumarate with the reduction of quinone to quinol
      (QH(2)). The interaction between ubiquinone and the Q-site of the protein appears
      to be mediated solely by hydrogen bonding between the O1 carbonyl group of the
      quinone and the side chain of a conserved tyrosine residue. In this work, SQR was
      co-crystallized with the ubiquinone binding-site inhibitor Atpenin A5 (AA5) to
      confirm the binding position of the inhibitor and reveal additional structural
      details of the Q-site. The electron density for AA5 was located within the same
      hydrophobic pocket as ubiquinone at, however, a different position within the
      pocket. AA5 was bound deeper into the site prompting further assessment using
      protein-ligand docking experiments in silico. The initial interpretation of the Q
      site was re-evaluated in the light of the new SQR-AA5 structure and protein
      ligand docking data. Two binding positions, the Q(1)-site and Q(2)-site, are
      proposed for the E. coli SQR quinone-binding site to explain these data. At the
      Q(2)-site, the side chains of a serine and histidine residue are suitably
      positioned to provide hydrogen bonding partners to the O4 carbonyl and methoxy
      groups of ubiquinone, respectively. This allows us to propose a mechanism for the
      reduction of ubiquinone during the catalytic turnover of the enzyme.

PMID- 16407192
TI  - Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15
      in human cells.
AB  - ISG15 is an interferon (IFN)-alpha/beta-induced ubiquitin-like protein that is
      conjugated to cellular proteins during innate immune responses to viral and
      bacterial infections. A recent proteomics study identified 158 human proteins
      targeted for ISG15 conjugation, including the ISG15 E1 and E2 enzymes (Ube1L and
      UbcH8, respectively) and a HECT E3 enzyme, Herc5. Like the genes encoding Ube1L
      and UbcH8, expression of Herc5 was also induced by IFN-beta, suggesting that
      Herc5 might be a component of the ISG15 conjugation system. Consistent with this,
      small interfering RNAs targeting Herc5 had a dramatic effect on overall ISG15
      conjugation in human cells, abrogating conjugation to the vast majority of ISG15
      target proteins in vivo. In addition, co-transfection of plasmids expressing
      ISG15, Ube1L, UbcH8, and Herc5 resulted in robust ISG15 conjugation in non-IFN
      treated cells, while the active-site cysteine mutant of Herc5 or a mutant lacking
      the RCC1 repeat region did not support ISG15 conjugation. These results
      demonstrate that Herc5 is required for conjugation of ISG15 to a broad spectrum
      of target proteins in human cells.

PMID- 16407193
TI  - Activation of p21-activated kinase 2 and its association with Nef are conserved
      in murine cells but are not sufficient to induce an AIDS-like disease in CD4C/HIV
      transgenic mice.
AB  - A well conserved feature of human immunodeficiency virus, type 1 (HIV-1) and
      simian immunodeficiency virus (SIV) Nef is the interaction with and activation of
      the human p21-activated kinase 2 (PAK2). The conservation of this interaction in
      other species and its significance for Nef pathogenesis in vivo are poorly
      documented. In the present study, we measured these parameters in Nef-expressing
      thymocytes, macrophages, and dendritic cells of a transgenic (Tg) mouse model of
      AIDS (CD4C/HIV). We found that Nef binds to and activates PAK2, but not PAK1 and 
      3, in these three cell subsets. Nef associates with only a small fraction of
      PAK2. The Nef-PAK2 complex also comprises beta-PIX-COOL. The impact of the Nef
      PAK2 association on disease development was also analyzed in Tg mice expressing
      10 different Nef mutant alleles. CD4C/HIV Tg mice expressing Nef alleles
      defective in Nef-PAK2 association (P69A, P72A/P75A, R105A/R106A, Delta56-66, or
      G2A (myristoylation site)) failed to develop disease of the non-lymphoid organs
      (kidneys and lungs). Among these, only Tg mice expressing Nef(P69A) and Nef(G2A)
      showed some depletion of CD4(+) T cells, although a down-regulation of the CD4
      surface protein was documented in all these Tg lines, except those expressing
      Nef(Delta56-66). Among other Tg mice expressing Nef mutants having conserved the
      Nef-PAK2 association (RD35AA, D174K, P147A/P150A, Delta8-17, and Delta25-65),
      only Tg mice expressing Nef(Delta8-17) develop kidney and lung diseases, but all
      showed partial CD4(+) T cell depletion despite some being defective for CD4 down
      regulation (RD35AA and D174K). Therefore, Nef can activate murine PAK2 and
      associate with a small fraction of it, as in human cells. Such activation and
      binding of PAK2 is clearly not sufficient but may be required to induce a
      multiorgan AIDS-like disease in Tg mice.

PMID- 16407194
TI  - The Pyrococcus exosome complex: structural and functional characterization.
AB  - The exosome is a conserved eukaryotic enzymatic complex that plays an essential
      role in many pathways of RNA processing and degradation. Here, we describe the
      structural characterization of the predicted archaeal exosome in solution using
      small angle x-ray scattering. The structure model calculated from the small angle
      x-ray scattering pattern provides an indication of the existence of a disk-shaped
      structure, corresponding to the "RNases PH ring" complex formed by the proteins
      aRrp41 and aRrp42. The RNases PH ring complex corresponds to the core of the
      exosome, binds RNA, and has phosphorolytic and polymerization activities. Three
      additional molecules of the RNA-binding protein aRrp4 are attached to the core as
      extended and flexible arms that may direct the substrates to the active sites of
      the exosome. In the presence of aRrp4, the activity of the core complex is
      enhanced, suggesting a regulatory role for this protein. The results shown here
      also indicate the participation of the exosome in RNA metabolism in Archaea, as
      was established in Eukarya.

PMID- 16407195
TI  - Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang
      structure for activity.
AB  - The fusion peptide of influenza hemagglutinin is crucial for cell entry of this
      virus. Previous studies showed that this peptide adopts a boomerang-shaped
      structure in lipid model membranes at the pH of membrane fusion. To examine the
      role of the boomerang in fusion, we changed several residues proposed to
      stabilize the kink in this structure and measured fusion. Among these, mutants
      E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities,
      and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and
      free energies of mutant peptides to model membranes and their ability to perturb
      lipid bilayer structures correlated well with the fusion activities of the parent
      full-length molecules. The structure of W14A determined by NMR and site-directed
      spin labeling features a flexible kink that points out of the membrane, in sharp
      contrast to the more ordered boomerang of the wild-type, which points into the
      membrane. A specific fixed angle boomerang structure is thus required to support
      membrane fusion.

PMID- 16407196
TI  - Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative
      phenotypes in a mouse model for DRPLA.
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative
      disease caused by polyglutamine expansion within the Atrophin-1 protein. To study
      the mechanism of this disease and to test potential therapeutic methods, we
      established Atro-118Q transgenic mice, which express in neurons a mutant human
      Atrophin-1 protein that contains an expanded stretch of 118 glutamines.
      Consistent with the results from previous studies on transgenic mice that
      expressed mutant Atrophin-1 with 65 glutamines, Atro-118Q mice exhibited several
      neurodegenerative phenotypes that are commonly seen in DRPLA patients, including
      ataxia, tremors, and other motor defects. Overexpression of wild-type human
      Atrophin-1 could not rescue the motor and survival defects in Atro-118Q mice,
      indicating that the mutant protein with polyglutamine expansion does not simply
      function in a dominant negative manner. Biochemical analysis of Atro-118Q mice
      revealed hypoacetylation of histone H3 in brain tissues and thus suggested that
      global gene repression is an underlying mechanism for neurodegeneration in this
      mouse model. We further show that intraperitoneal administration of sodium
      butyrate, a histone deacetylase inhibitor, ameliorated the histone acetylation
      defects, significantly improved motor performance, and extended the average life
      span of Atro-118Q mice. These results support the hypothesis that transcription
      deregulation plays an important role in the pathogenesis of polyglutamine
      expansion diseases and suggest that reversion of transcription repression with
      small molecules such as sodium butyrate is a feasible approach to treating DRPLA
      symptoms.

PMID- 16407197
TI  - Real time single cell analysis of Bid cleavage and Bid translocation during
      caspase-dependent and neuronal caspase-independent apoptosis.
AB  - Bcl-2 homology domain (BH) 3-only proteins couple stress signals to
      evolutionarily conserved mitochondrial apoptotic pathways. Caspase 8-mediated
      cleavage of the BH3-only protein Bid into a truncated protein (tBid) and
      subsequent translocation of tBid to mitochondria has been implicated in death
      receptor signaling. We utilized a recombinant fluorescence resonance energy
      transfer (FRET) Bid probe to determine the kinetics of Bid cleavage and tBid
      translocation during death receptor-induced apoptosis in caspase 3-deficient MCF
      7 cells. Cells treated with tumor necrosis factor-alpha (200 ng/ml) showed a
      rapid cleavage of the Bid-FRET probe occurring 75.4 +/- 12.6 min after onset of
      the tumor necrosis factor-alpha exposure. Cleavage of the Bid-FRET probe
      coincided with a translocation of tBid to the mitochondria and a collapse of the
      mitochondrial membrane potential (DeltaPsim). We next investigated the role of
      Bid cleavage in a model of caspase-independent, glutamate-induced excitotoxic
      apoptosis. Rat cerebellar granule neurons were transfected with the Bid-FRET
      probe and exposed to glutamate for 5 min. In contrast to death receptor-induced
      apoptosis, neurons showed a translocation of full-length Bid to the mitochondria.
      This translocation occurred 5.6 +/- 1.7 h after the termination of the glutamate
      exposure and was also paralleled with a collapse of the DeltaPsim. Proteolytic
      cleavage of the FRET probe also occurred, however, only 25.2 +/- 3.5 min after
      its translocation to the mitochondria. Subfractionation experiments confirmed a
      translocation of full-length Bid from the cytosolic to the mitochondrial fraction
      during excitotoxic apoptosis. Our data demonstrate that both tBid and full-length
      Bid have the capacity to translocate to mitochondria during apoptosis.

PMID- 16407198
TI  - The structure of Leishmania mexicana ICP provides evidence for convergent
      evolution of cysteine peptidase inhibitors.
AB  - Clan CA, family C1 cysteine peptidases (CPs) are important virulence factors and
      drug targets in parasites that cause neglected diseases. Natural CP inhibitors of
      the I42 family, known as ICP, occur in some protozoa and bacterial pathogens but
      are absent from metazoa. They are active against both parasite and mammalian CPs,
      despite having no sequence similarity with other classes of CP inhibitor. Recent
      data suggest that Leishmania mexicana ICP plays an important role in host
      parasite interactions. We have now solved the structure of ICP from L. mexicana
      by NMR and shown that it adopts a type of immunoglobulin-like fold not previously
      reported in lower eukaryotes or bacteria. The structure places three loops
      containing highly conserved residues at one end of the molecule, one loop being
      highly mobile. Interaction studies with CPs confirm the importance of these loops
      for the interaction between ICP and CPs and suggest the mechanism of inhibition.
      Structure-guided mutagenesis of ICP has revealed that residues in the mobile loop
      are critical for CP inhibition. Data-driven docking models support the importance
      of the loops in the ICP-CP interaction. This study provides structural evidence
      for the convergent evolution from an immunoglobulin fold of CP inhibitors with a
      cystatin-like mechanism.

PMID- 16407199
TI  - Leukemia inhibitory factor induces endothelial differentiation in cardiac stem
      cells.
AB  - The importance of interleukin 6 (IL-6)-related cytokines in cardiac homeostasis
      has been studied extensively; however, little is known about their biological
      significance in cardiac stem cells. Here we describe that leukemia inhibitory
      factor (LIF), a member of IL-6-related cytokines, activated STAT3 and ERK1/2 in
      cardiac Sca-1+ stem cells. LIF stimulation resulted in the induction of
      endothelial cell-specific genes, including VE-cadherin, Flk-1, and CD31, whereas
      neither smooth muscle nor cardiac muscle marker genes such as GATA4, GATA6, Nkx
      2.5, and calponin were up-regulated. Immunocytochemical examination showed that
      about 25% of total cells were positively stained with anti-CD31 antibody 14 days
      after LIF stimulation. Immunofluorescent microscopic analyses identified the Sca
      1+ cells that were also positively stained with anti-von Willebrand factor
      antibody, indicating the differentiating process of Sca-1+ cells into the
      endothelial cells. IL-6, which did not activate STAT3 and ERK1/2, failed to
      induce the differentiation of cardiac stem cells into the endothelial cells. In
      cardiac stem cells, the transduction with dominant negative STAT3 abrogated the
      LIF-induced endothelial differentiation. And the inhibition of ERK1/2 with the
      MEK1/2 inhibitor U0126 also prevented the differentiation of Sca-1+ cells into
      endothelial cells. Thus, both STAT3 and ERK1/2 are required for LIF-mediated
      endothelial differentiation in cardiac stem cells. Collectively, it is proposed
      that LIF regulates the commitment of cardiac stem cells into the endothelial cell
      lineage, contributing to neovascularization in the process of tissue remodeling
      and/or regeneration.

PMID- 16407200
TI  - TAB-1 modulates intracellular localization of p38 MAP kinase and downstream
      signaling.
AB  - Stress-activated mitogen-activated protein (MAP) kinase p38 mediates stress
      signaling in mammalian cells via threonine and tyrosine phosphorylation in its
      conserved TGY motif by upstream MAP kinase kinases (MKKs). In addition, p38 MAP
      kinase can also be activated by an MKK-independent mechanism involving TAB-1 (TAK
      1-binding protein)-mediated autophosphorylation. Although TAB-1-mediated p38
      activation has been implicated in ischemic heart, the biological consequences and
      downstream signaling of TAB-1-mediated p38 activation in cardiomyocytes is
      largely unknown. We show here that TAB-1 expression leads to a significant
      induction of p38 autophosphorylation and consequent kinase activation in cultured
      neonatal cardiomyocytes. In contrast to MKK3-induced p38 kinase downstream
      effects, TAB-1-induced p38 kinase activation does not induce expression of pro
      inflammatory genes, cardiac marker gene expression, or changes in cellular
      morphology. Rather, TAB-1 binds to p38 and prevents p38 nuclear localization.
      Furthermore, TAB-1 disrupts p38 interaction with MKK3 and redirects p38
      localization in the cytosol. Consequently, TAB-1 expression antagonizes the
      downstream activity of p38 kinase induced by MKK3 and attenuates interleukin
      1beta-induced inflammatory gene induction in cardiomyocytes. These data suggest
      that TAB-1 can mediate MKK-independent p38 kinase activation while negatively
      modulating MKK-dependent p38 function. Our study not only redefines the
      functional role of TAB-1 in p38 kinase-mediated signaling pathways but also
      provides the first evidence that intracellular localization of p38 kinase and
      complex interaction dictates its downstream effects. These results suggest a
      previously unknown mechanism for stress-MAP kinase regulation in mammalian cells.

PMID- 16407201
TI  - Gbetagamma inhibits Galpha GTPase-activating proteins by inhibition of Galpha-GTP
      binding during stimulation by receptor.
AB  - Gbetagamma subunits modulate several distinct molecular events involved with G
      protein signaling. In addition to regulating several effector proteins,
      Gbetagamma subunits help anchor Galpha subunits to the plasma membrane, promote
      interaction of Galpha with receptors, stabilize the binding of GDP to Galpha to
      suppress spurious activation, and provide membrane contact points for G protein
      coupled receptor kinases. Gbetagamma subunits have also been shown to inhibit the
      activities of GTPase-activating proteins (GAPs), both phospholipase C (PLC)-betas
      and RGS proteins, when assayed in solution under single turnover conditions. We
      show here that Gbetagamma subunits inhibit G protein GAP activity during receptor
      stimulated, steady-state GTPase turnover. GDP/GTP exchange catalyzed by receptor
      requires Gbetagamma in amounts approximately equimolar to Galpha, but GAP
      inhibition was observed with superstoichiometric Gbetagamma. The potency of
      inhibition varied with the GAP and the Galpha subunit, but half-maximal
      inhibition of the GAP activity of PLC-beta1 was observed with 5-10 nM Gbetagamma,
      which is at or below the concentrations of Gbetagamma needed for regulation of
      physiologically relevant effector proteins. The kinetics of GAP inhibition of
      both receptor-stimulated GTPase activity and single turnover, solution-based GAP
      assays suggested a competitive mechanism in which Gbetagamma competes with GAPs
      for binding to the activated, GTP-bound Galpha subunit. An N-terminal truncation
      mutant of PLC-beta1 that cannot be directly regulated by Gbetagamma remained
      sensitive to inhibition of its GAP activity, suggesting that the Gbetagamma
      binding site relevant for GAP inhibition is on the Galpha subunit rather than on
      the GAP. Using fluorescence resonance energy transfer between cyan or yellow
      fluorescent protein-labeled G protein subunits and Alexa532-labeled RGS4, we
      found that Gbetagamma directly competes with RGS4 for high-affinity binding to
      Galpha(i)-GDP-AlF4.

PMID- 16407202
TI  - Equilibrium between metarhodopsin-I and metarhodopsin-II is dependent on the
      conformation of the third cytoplasmic loop.
AB  - Rhodopsin is a G-protein-coupled receptor (GPCR) that is the light detector in
      the rod cells of the eye. Rhodopsin is the best understood member of the large
      GPCR superfamily and is the only GPCR for which atomic resolution structures have
      been determined. However, these structures are for the inactive, dark-adapted
      form. Characterization of the conformational changes in rhodopsin caused by light
      induced activation is of wide importance, because the metarhodopsin-II
      photoproduct is analogous to the agonist-occupied conformation of other GPCRs,
      and metarhodopsin-I may be similar to antagonist-occupied GPCR conformations. In
      this work we characterize the interaction of antibody K42-41L with the
      metarhodopsin photoproducts. K42-41L is shown to inhibit formation of
      metarhodopsin-II while it stabilizes the metarhodopsin-I state. Thus, K42-41L
      recognizes an epitope accessible in dark-adapted rhodopsin and metarhodopsin-I
      that is lost upon formation of metarhodopsin-II. Previous work has shown that the
      peptide TGALQERSK is able to mimic the K42-41L epitope, and we have now
      determined the structure of the K42-41L-peptide complex. The structure
      demonstrates a central role for elements of the rhodopsin C3 loop, particularly
      Gln238 and Glu239, in the interaction with K42-41L. Geometric constraints taken
      from the antibody-bound peptide were used to model the epitope on the rhodopsin
      surface. The resulting model suggests that K42-41L locks the C3 loop into an
      extended conformation that is intermediate between two compact conformations seen
      in crystal structures of dark-adapted rhodopsin. Together, the structural and
      functional data strongly suggest that the equilibrium between metarhodopsin-I and
      metarhodopsin-II is dependent upon the conformation of the C3 loop. The
      biological implications of this model and its possible relations to dimeric and
      multimeric complexes of rhodopsin are discussed.

PMID- 16407203
TI  - Annular arrangement and collaborative actions of four domains of protein
      disulfide isomerase: a small angle X-ray scattering study in solution.
AB  - We presented for the first time a small angle x-ray scattering study of intact
      protein-disulfide isomerase (PDI) in solution. The restored model revealed that
      PDI is a short and roughly elliptical cylinder with a molecular mass of 69 kDa
      and dimensions of 105 x 65 x 40 A, and the four thioredoxin-fold domains in the
      order a-b-b'-a' are arranged in an annular fashion. Atomic force microscope
      imaging also supported the finding that PDI appears as an approximately flat
      elliptical cylinder. A PDI species with apparent molecular mass of 116 kDa
      measured by using size-exclusion chromatography, previously assumed to be a
      dimer, was determined to exist mainly as a monomer by using analytical
      ultracentrifugation. The C-terminal fragment 441-491 contributed to the anomalous
      molecular mass determination of PDI by size-exclusion chromatography. The annular
      model of PDI accounted for the cooperative properties of the four domains in both
      the isomerase and chaperone functions of PDI.

PMID- 16407205
TI  - Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan
      fragments.
AB  - Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that interacts with
      cell-surface receptors, including CD44. Although HA usually exists as a high
      molecular mass polymer, HA of a much lower molecular mass that shows a variety of
      biological activities can be detected under certain pathological conditions,
      particularly in tumors. We previously reported that low molecular weight HAs (LMW
      HAs) of a certain size range induce the proteolytic cleavage of CD44 from the
      surface of tumor cells and promote tumor cell migration in a CD44-dependent
      manner. Here, we show that MIA PaCa-2, a human pancreatic carcinoma cell line,
      secreted hyaluronidases abundantly and generated readily detectable levels of LMW
      HAs ranging from approximately 10- to 40-mers. This occurred in the absence of
      any exogenous stimulation. The tumor-derived HA oligosaccharides were able to
      enhance CD44 cleavage and tumor cell motility. Inhibition of the CD44-HA
      interaction resulted in the complete abrogation of these cellular events. These
      results are consistent with the concept that tumor cells generate HA oligosaccha
      rides that bind to tumor cell CD44 through the expression of their own
      constitutive hyaluronidases. This enhances their own CD44 cleavage and cell
      motility, which would subsequently promote tumor progression. Such an
      autocrine/paracrine-like process may represent a novel activation mechanism that
      would facilitate and promote the malignant potential of tumor cells.

PMID- 16407204
TI  - Intracellular trafficking and secretion of adiponectin is dependent on GGA-coated
      vesicles.
AB  - Adiponectin (Acrp30) is an insulin-sensitizing hormone produced and secreted
      exclusively by adipose tissue. Confocal fluorescent microscopy demonstrated the
      colocalization of adiponectin with the Golgi membrane markers p115, beta-COP, and
      the trans-Golgi network marker, syntaxin 6. Treatment of cells with brefeldin A
      redistributed adiponectin to the endoplasmic reticulum where it colocalized with
      the chaperone protein BIP and inhibited secretion of adiponectin demonstrating a
      requirement for a functional Golgi apparatus for adiponectin release. Confocal
      fluorescent microscopy also demonstrated a colocalization of endogenous
      adiponectin with that of expressed GGA1myc (Golgi-localizing gamma-adaptin ear
      homology ARF-binding protein) but with no significant overlap between adiponectin
      and the GGA2myc or GGA3myc isoforms. Consistent with confocal fluorescent
      microscopy, transmission electron microscopy demonstrated the colocalization of
      GGA1 with adiponectin. Although GGA1 did not directly interact with the
      adiponectin protein, the adiponectin enriched membrane compartments of adipocyte
      were precipitated by a GST-GGA1 cargo binding domain (VHS) fusion protein but not
      with a GST-GGA2 VHS or GST-GGA3 VHS fusion proteins. Moreover, co-expression of
      adiponectin with a GGA1 dominant-interfering mutant (GGA1-VHS GAT domain)
      resulted in a marked inhibition of adiponectin secretion in both 3T3L1 adipocytes
      and HEK293 cells, whereas no inhibition was detected with the truncated mutants
      GGA2-VHSGAT or GGA3-VHSGAT. Moreover, co-expression of wild type GGA1 with
      adiponectin enhanced secretion of adiponectin. Interestingly, leptin secretion
      was unaffected by neither the wild type form or GGA1 mutant. Taken together these
      data demonstrate that the trafficking of adiponectin through its secretory
      pathway is dependent on GGA-coated vesicles.

PMID- 16407206
TI  - Chronic inhibition of cardiac Kir2.1 and HERG potassium channels by celastrol
      with dual effects on both ion conductivity and protein trafficking.
AB  - A high percentage of drugs and drug candidates has been found to cause
      cardiotoxicity by reducing potassium conductance, more commonly known as QT
      prolongation. However, some compounds do not show direct block of ionic flow,
      suggesting that other mechanisms may also lead to reduction of potassium
      currents. Using the functional recovery after chemobleaching (FRAC) assay, we
      have examined a collection of drugs and drug-like compounds for potential
      perturbation of cardiac potassium channel trafficking. Here we report that a
      significant number of inhibitory compounds displayed effects on channel
      expression on the cell surface. Further investigation of celastrol (3-hydroxy-24
      nor-2-oxo-1 (10),3,5,7-friedelatetraen-29-oic acid), a cell-permeable
      dienonephenolic triterpene compound, revealed its potent inhibitory activity on
      both Kir2.1 and hERG potassium channels, causal to QT prolongation. In addition
      to acute block of ion conduction, celastrol also alters the rate of ion channel
      transport and causes a reduction of channel density on the cell surface. In
      contrast, celastrol has no effects on trafficking of either CD4 or CD8 membrane
      proteins. Furthermore, the potency for reducing surface expression is
      approximately 5-10-fold more effective than that for either direct acute
      inhibition or reported cytoprotectivity via activation of the heat shock
      transcription factor 1. Because the reduction of potassium channel activity is a
      common form of druginduced cardiotoxicity, the potent inhibition of cell surface
      expression by celastrol underscores a need to evaluate drug candidates for their
      chronic effects on biogenesis of potassium channels. Our results suggest that
      chronic exposure to certain drugs may be an important aspect of acquired QT
      prolongation.

PMID- 16407207
TI  - Nhp6 is a transcriptional initiation fidelity factor for RNA polymerase III
      transcription in vitro and in vivo.
AB  - The binding of the RNA polymerase III (pol III) transcription factor TFIIIC to
      the box A intragenic promoter element of tRNA genes specifies the placement of
      TFIIIB on upstream-lying DNA. In turn, TFIIIB recruits pol III to the promoter
      and specifies transcription initiating 17-19 base pairs upstream of box A. The
      resolution of the pol III transcription apparatus into recombinant TFIIIB, highly
      purified TFIIIC, and pol III is accompanied by a loss of precision in specifying
      where transcription initiation occurs due to heterogeneous placement of TFIIIB.
      In this paper we show that Nhp6a, an abundant high mobility group B (HMGB)
      family, non-sequence-specific DNA-binding protein in Saccharomyces cerevisiae
      restores transcriptional initiation fidelity to this highly purified in vitro
      system. Restoration of initiation fidelity requires the presence of Nhp6a prior
      to TFIIIB-DNA complex formation. Chemical nuclease footprinting of TFIIIC- and
      TFIIIB-TFIIIC-DNA complexes reveals that Nhp6a markedly alters the TFIIIC
      footprint over box A and reduces the size of the TFIIIB footprint on upstream DNA
      sequence. Analyses of unprocessed tRNAs from yeast lacking Nhp6a and its closely
      related paralogue Nhp6b demonstrate that Nhp6 is required for transcriptional
      initiation fidelity of some but not all tRNA genes, in vivo.

PMID- 16407208
TI  - Age-dependent participation of Ras-GRF proteins in coupling calcium-permeable
      AMPA glutamate receptors to Ras/Erk signaling in cortical neurons.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate
      receptors (AMPARs) are ligand-gated sodium channels. Through their ability to
      mediate the majority of rapid excitatory transmission in the central nervous
      system, these neurotransmitter receptors have been shown to influence synaptic
      plasticity. Some of these receptors are also calcium-permeable (CP), and they
      also have been implicated in regulating synaptic plasticity, particularly in
      interneurons where their concentration is highest. However, the biochemical
      pathways emanating from CP-AMPARs that mediate these effects have not been well
      characterized. In this paper, we show that CP-AMPARs are the predominant AMPAR
      class responsible for activating the Ras/Erk kinase signaling cascade and the
      cAMP-response element-binding protein (CREB) transcription factor in the cortex
      of mature mice. Activation of Ras and Erk, but not CREB, occurs through the
      calcium/calmodulin regulated Ras-GRF1 and Ras-GRF2 exchange factors, which form
      AMPA-induced complexes with CP-AMPARs but not calcium-impermeable (CI) AMPARs in
      vivo. Furthermore, we show that CP-AMPARs are also the major AMPAR type to
      activate Ras/Erk signaling in pubescent mice; however, at this developmental
      stage Ras-GRF (guanine nucleotide-releasing factor) proteins are not involved.
      Finally, in neonatal animals CI-AMPARs, but not CP-AMPARs, are the predominant
      AMPAR type that activates Ras-Erk signaling and CREB in cortical neurons. This
      occurs indirectly through activation of L-type voltage-dependent calcium
      channels, an event that is also Ras-GRF-independent. Thus, Ras/Erk signaling and
      CREB activity induced by AMPARs occur through age-dependent mechanisms that
      likely make unique developmentally dependent contributions to synaptic function.

PMID- 16407209
TI  - Phosphorylation marks IPF1/PDX1 protein for degradation by glycogen synthase
      kinase 3-dependent mechanisms.
AB  - The transcription factor IPF1/PDX1 plays a crucial role in both pancreas
      development and maintenance of beta-cell function. Targeted disruption of this
      transcription factor in beta-cells leads to diabetes, whereas reduced expression
      levels affect insulin expression and secretion. Therefore, it is essential to
      determine molecular mechanisms underlying the regulation of this key
      transcription factor on mRNA levels and, most importantly, on protein levels.
      Here we show that a minor portion of IPF1/PDX1 is phosphorylated on serine 61
      and/or serine 66 in pancreatic beta-cells. This phosphorylated form of IPF1/PDX1
      preferentially accumulates following proteasome inhibition, an effect that is
      prevented by inhibition of glycogen synthase kinase 3 (GSK3) activity. Oxidative
      stress, which is associated with the diabetic state, (i) increases IPF1/PDX1
      Ser61 and/or Ser66 phosphorylation and (ii) increases the degradation rate and
      decreases the half-life of IPF-1/PDX-1 protein. In addition, we provide evidence
      that GSK3 activity participates in oxidative stress-induced effects on beta
      cells. Thus, this current study uncovers a new mechanism that might contribute to
      diminished levels of IPF1/PDX1 protein and beta-cell dysfunction during the
      progression of diabetes.

PMID- 16407210
TI  - Single amino acid substitution in the PC1/3 propeptide can induce significant
      modifications of its inhibitory profile toward its cognate enzyme.
AB  - The proprotein convertase PC1/3 is synthesized as a large precursor that
      undergoes proteolytic processing of the signal peptide, the propeptide and
      ultimately the COOH-terminal tail, to generate the mature form. The propeptide is
      essential for protease folding, and, although cleaved by an autocatalytic
      process, it remains associated with the mature form acting as an auto-inhibitor
      of PC1/3. To further assess the role of certain residues in its interaction with
      its cognate enzyme, we performed an alanine scan on two PC1/3 propeptide
      potential cleavable sites ((50)RRSRR(54) and (61)KR(62)) and an acidic region
      (65)DDD(67) conserved among species. Upon incubation with PC1/3, the ensuing
      peptides exhibit equal inhibitory potency, lower potency, or higher potency than
      the wild-type propeptide. The K(i) values calculated varied between 0.15 and 16.5
      nm. All but one mutant exhibited a tight binding behavior. To examine the
      specificity of mutants, we studied their reactivity toward furin, a closely
      related convertase. The mutation of certain residues also affects the inhibition
      behavior toward furin yielding propeptides exhibiting K(i) ranging from 0.2 to 24
      nm. Mutant propeptides exhibited against each enzyme either different mode of
      inhibition, enhanced selectivity in the order of 40-fold for one enzyme, or high
      potency with no discrimination. Hence, we demonstrate through single amino acid
      substitution that it is feasible to modify the inhibitory behavior of propeptides
      toward convertases in such a way as to increase or decrease their potency, modify
      their inhibitory mechanisms, as well as increase their selectivity.

PMID- 16407211
TI  - Structure and reactivity of a thermostable prokaryotic nitric-oxide synthase that
      forms a long-lived oxy-heme complex.
AB  - In an effort to generate more stable reaction intermediates involved in substrate
      oxidation by nitric-oxide synthases (NOSs), we have cloned, expressed, and
      characterized a thermostable NOS homolog from the thermophilic bacterium
      Geobacillus stearothermophilus (gsNOS). As expected, gsNOS forms nitric oxide
      (NO) from l-arginine via the stable intermediate N-hydroxy l-arginine (NOHA). The
      addition of oxygen to ferrous gsNOS results in long-lived heme-oxy complexes in
      the presence (Soret peak 427 nm) and absence (Soret peak 413 nm) of substrates l
      arginine and NOHA. The substrate-induced red shift correlates with hydrogen
      bonding between substrate and heme-bound oxygen resulting in conversion to a
      ferric heme-superoxy species. In single turnover experiments with NOHA, NO forms
      only in the presence of H(4)B. The crystal structure of gsNOS at 3.2 AA of
      resolution reveals great similarity to other known bacterial NOS structures, with
      the exception of differences in the distal heme pocket, close to the oxygen
      binding site. In particular, a Lys-356 (Bacillus subtilis NOS) to Arg-365 (gsNOS)
      substitution alters the conformation of a conserved Asp carboxylate, resulting in
      movement of an Ile residue toward the heme. Thus, a more constrained heme pocket
      may slow ligand dissociation and increase the lifetime of heme-bound oxygen to
      seconds at 4 degrees C. Similarly, the ferric-heme NO complex is also stabilized
      in gsNOS. The slow kinetics of gsNOS offer promise for studying downstream
      intermediates involved in substrate oxidation.

PMID- 16407212
TI  - Reverse gyrase functions as a DNA renaturase: annealing of complementary single
      stranded circles and positive supercoiling of a bubble substrate.
AB  - Reverse gyrase is a hyperthermophile-specific enzyme that can positively
      supercoil DNA concomitant with ATP hydrolysis. However, the DNA supercoiling
      activity is inefficient and requires an excess amount of enzyme relative to DNA.
      We report here several activities that reverse gyrase can efficiently mediate
      with a substoichiometric amount of enzyme. In the presence of a nucleotide
      cofactor, reverse gyrase can readily relax negative supercoils, but not the
      positive ones, from a plasmid DNA substrate. Reverse gyrase can completely relax
      positively supercoiled DNA, provided that the DNA substrate contains a single
      stranded bubble. Reverse gyrase efficiently anneals complementary single-stranded
      circles. A substoichiometric amount of reverse gyrase can insert positive
      supercoils into DNA with a single-stranded bubble, in contrast to plasmid DNA
      substrate. We have designed a novel method based on phage-mid DNA vectors to
      prepare a circular DNA substrate containing a single-stranded bubble with defined
      length and sequence. With these bubble DNA substrates, we demonstrated that
      efficient positive supercoiling by reverse gyrase requires a bubble size larger
      than 20 nucleotides. The activities of annealing single-stranded DNA circles and
      positive supercoiling of bubble substrate demonstrate that reverse gyrase can
      function as a DNA renaturase. These biochemical activities also suggest that
      reverse gyrase can have an important biological function in sensing and
      eliminating unpaired regions in the genome of a hyperthermophilic organism.

PMID- 16407213
TI  - Organelle proteomics reveals cargo maturation mechanisms associated with Golgi
      like encystation vesicles in the early-diverged protozoan Giardia lamblia.
AB  - During encystation Giardia trophozoites secrete a fibrillar extracellular matrix
      of glycans and cyst wall proteins on the cell surface. The cyst wall material is
      accumulated in encystation-specific vesicles (ESVs), specialized Golgi-like
      compartments generated de novo, after export from the endoplasmic reticulum (ER)
      and before secretion. These large post-ER vesicles neither have the morphological
      characteristics of Golgi cisternae nor sorting functions, but may represent an
      evolutionary early form of the Golgi-like maturation compartment. Because little
      is known about the genesis and maturation of ESVs, we used a limited proteomics
      approach to discover novel proteins that are specific for developing ESVs or
      associated peripherally with these organelles. Unexpectedly, we identified
      cytoplasmic and luminal factors of the ER quality control system on two
      dimensional electrophoresis gels, i.e. several proteasome subunits and HSP70-BiP.
      We show that BiP is exported to ESVs and retrieved via its C-terminal KDEL signal
      from ESVs. In contrast, cytoplasmic proteasome complexes undergo a
      developmentally regulated re-localization to ESVs during encystation. This
      suggests that maturation of bulk exported cyst wall material in the Golgi-like
      ESVs involves both continuous activity of ER-associated quality control
      mechanisms and retrograde Golgi to ER transport.

PMID- 16407214
TI  - Epidermal growth factor receptor exposed to oxidative stress undergoes Src- and
      caveolin-1-dependent perinuclear trafficking.
AB  - The epidermal growth factor (EGF) receptor (EGFR) has been found to be
      overexpressed in several types of cancer cells, and the regulation of its
      oncogenic potential has been widely studied. The paradigm for EGFR down
      regulation involves the trafficking of activated receptor molecules from the
      plasma membrane, through clathrin-coated pits, and into the cell for lysosomal
      degradation. We have previously shown that oxidative stress generated by H2O2
      results in aberrant phosphorylation of the EGFR. This leads to the loss of c-Cbl
      mediated ubiquitination of the EGFR and, consequently, prevents its degradation.
      However, we have found that c-Cbl-mediated ubiquitination is required solely for
      degradation but not for internalization of the EGFR under oxidative stress. To
      further examine the fate of the EGFR under oxidative stress, we used confocal
      analysis to show that the receptor not only remains co-localized with caveolin-1
      at the plasma membrane, but at longer time points, is also sorted to a
      perinuclear compartment via a clathrin-independent, caveolae-mediated pathway.
      Our findings indicate that although the EGFR associates with caveolin-1
      constitutively, caveolin-1 is hyperphosphorylated only under oxidative stress,
      which is essential in transporting the EGFR to a perinuclear location, where it
      is not degraded and remains active. Thus, oxidative stress may have a role in
      tumorigenesis by not only activating the EGFR but also by promoting prolonged
      activation of the receptor both at the plasma membrane and within the cell.

PMID- 16407216
TI  - IKK alpha regulates estrogen-induced cell cycle progression by modulating E2F1
      expression.
AB  - The IkappaB kinase (IKK) complex consists of the catalytic subunits IKKalpha and
      IKKbeta and a regulatory subunit, IKKgamma/NEMO. Even though IKKalpha and IKKbeta
      share significant sequence similarity, they have distinct biological roles. It
      has been demonstrated that IKKs are involved in regulating the proliferation of
      both normal and tumor cells, although the mechanisms by which they function in
      this process remain to be better defined. In this study, we demonstrate that
      IKKalpha, but not IKKbeta, is important for estrogen-induced cell cycle
      progression by regulating the transcription of the E2F1 gene as well as other
      E2F1-responsive genes, including thymidine kinase 1, proliferating cell nuclear
      antigen, cyclin E, and cdc25A. The role of IKKalpha in regulating E2F1 was not
      the result of reduced levels of cyclin D1, as overexpression of this gene could
      not overcome the effects of IKKalpha knock-down. Furthermore, estrogen treatment
      increased the association of endogenous IKKalpha and E2F1, and this interaction
      occurred on promoters bound by E2F1. IKKalpha also potentiated the ability of
      p300/CBP-associated factor to acetylate E2F1. Taken together, these data suggest
      a novel mechanism by which IKKalpha can influence estrogen-mediated cell cycle
      progression through its regulation of E2F1.

PMID- 16407215
TI  - Self-association and lipid binding properties of the lipoprotein initiating
      domain of apolipoprotein B.
AB  - The amino-terminal 20.1% of apolipoprotein B (apoB20.1; residues 1-912) is
      sufficient to initiate and direct the formation of nascent apoB-containing
      lipoprotein particles. To investigate the mechanism of initial lipid acquisition
      by apoB, we examined the lipid binding and interfacial properties of a carboxyl
      terminal His6-tagged form of apoB20.1 (apoB20.1H). ApoB20.1H was expressed in Sf9
      cells and purified by nickel affinity chromatography. ApoB20.1H was produced in a
      folded state as characterized by formation of intramolecular disulfide bonds and
      resistance to chemical reduction. Dynamic light scattering in physiological
      buffer indicated that purified apoB20.1H formed multimers, which were readily
      dissociable upon the addition of nonionic detergent (0.1% Triton X-100).
      ApoB20.1H was incapable of binding dimyristoylphosphatidylcholine multilamellar
      vesicles, unless its multimeric structure was first disrupted by guanidine
      hydrochloride. However, apoB20.1H multimers spontaneously dissociated and bound
      to the interface of naked and phospholipid-coated triolein droplets. These data
      reveal that the initiating domain of apoB contains solvent-accessible hydrophobic
      sequences, which, in the absence of a hydrophobic lipid interface or detergent,
      engage in self-association. The high affinity of apoB20.1H for neutral lipid is
      consistent with the membrane binding and desorption model of apoB-containing
      lipoprotein assembly.

PMID- 16407217
TI  - Antianoikis effect of nuclear factor-kappaB through up-regulated expression of
      osteoprotegerin, BCL-2, and IAP-1.
AB  - Epithelial cells undergo a form of apoptosis termed anoikis when they lose
      extracellular attachments. We evaluated the role of transcription factor NF
      kappaB in the regulation of anoikis susceptibility of intestinal epithelial
      cells. Culture of rat intestinal epithelial cells in suspension induced NF-kappaB
      activation, which blocked the anoikis of those cells, as assessed by
      internucleosomal DNA fragmentation and caspase-3 cleavage. Activation of NF
      kappaB after the loss of extracellular attachments required focal adhesion kinase
      tyrosine 397 phosphorylation. This triggered a signaling cascade through
      phosphatidylinositol 3-kinase and AKT, to induce DNA binding of the RelA/p65 NF
      kappaB polypeptide. NF-kappaB activated in this manner induced the up-regulated
      expression of a distinct program of genes that included osteoprotegerin, BCL-2,
      and IAP-1 (inhibitor of apoptosis protein-1). Chromatin immunoprecipitation
      experiments revealed that NF-kappaB directly regulated the promoters of these 3
      genes. Knock-down of the expression of osteoprotegerin, BCL-2, or inhibitor of
      apoptosis protein-1 by RNA interference showed that these factors inhibit
      anoikis, and genetic reconstitution of their expression alone or in combination
      restored normal levels of anoikis to NF-kappaB-inactive intestinal epithelial
      cells. Together, these findings have identified the molecular components of a
      previously unrecognized antianoikis pathway in intestinal epithelial cells.

PMID- 16407218
TI  - Interaction of mannan binding lectin with alpha2 macroglobulin via exposed
      oligomannose glycans: a conserved feature of the thiol ester protein family?
AB  - The serum collectin mannan-binding lectin (MBL) binds to oligomannose and GlcNAc
      terminating glycans present on microorganisms. Using a commercial affinity
      chromatography resin containing immobilized MBL we screened human and mouse serum
      for endogenous MBL-binding targets. We isolated the serum protease inhibitor
      alpha(2) macroglobulin (alpha2M), a heavily glycosylated thiol ester protein
      (TEP) composed of four identical 180-kDa subunits, each of which has eight N
      linked glycosylation sites. alpha2M has previously been reported to interact with
      MBL; however, the interaction was not characterized. We investigated the
      mechanism of formation of complexes between alpha2M and MBL and concluded that
      they form by the direct binding of oligomannose glycans Man(5-7) occupying Asn
      846 on alpha2M to the lectin domains (carbohydrate recognition domains) of MBL.
      The oligomannose glycans are accessible for lectin binding on both active alpha2M
      (thiol ester intact) and protease-cleaved alpha2M (thiol ester cleaved). We
      demonstrate that MBL is able to interact with alpha2M in the fluid phase, but the
      interaction does not inhibit the binding of MBL to mannan-coated surfaces. In
      addition to alpha2M, two other members of the TEP family, C3 and C4, which also
      contain oligomannose glycans, were captured from human serum using the MBL resin.
      MBL binding may be a conserved feature of the TEPs, dating from their ancestral
      origins. We suggest that the inhibition of proteases on the surface of
      microorganisms by an ancestral alpha2M-like TEP may generate "arrays" of
      oligomannose glycans to which MBL or other lectins can bind. Binding would lead
      to opsonization or activation of enzyme systems such as complement.

PMID- 16407219
TI  - In vitro reconstitution of catabolite repression in Escherichia coli.
AB  - A widely accepted model for catabolite repression posits that phospho-IIAGlc of
      the bacterial phosphotransferase system activates adenylyl cyclase (AC) activity.
      For many years, attempts to observe such regulatory properties of AC in vitro
      have been unsuccessful. To further study the regulation, AC was produced fused to
      the transmembrane segments of the serine chemoreceptor Tsr. Cells harboring Tsr
      AC and normal AC, expressed from the cya promoter on a low copy number vector,
      exhibit similar behavior with respect to elevation of cAMP levels resulting from
      deletion of crp, expressing the catabolite regulatory protein. Membrane-bound Tsr
      AC exhibits activity comparable with the native form of AC. Tsr-AC binds IIAGlc
      specifically, regardless of its phosphorylation state, but not the two general
      phosphotransferase system proteins, enzyme I and HPr; IIAGlc binding is localized
      to the C-terminal region of AC. Binding to membranes of either dephospho- or
      phospho-IIAGlc has no effect on AC activity. However, in the presence of an
      Escherichia coli extract, P-IIAGlc, but not IIAGlc, stimulates AC activity. Based
      on these findings of a direct interaction of IIAGlc with AC, but activity
      regulation only in the presence of E. coli extract, a revised model for AC
      activity regulation is proposed.

PMID- 16407220
TI  - Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP
      activated protein kinase in cultured endothelial cells.
AB  - We previously reported the phosphoinositide 3-kinase-dependent activation of the
      5'-AMP-activated kinase (AMPK) by peroxynitrite (ONOO-) and hypoxia-reoxygenation
      in cultured endothelial cells. Here we show the molecular mechanism of activation
      of this pathway. Exposure of bovine aortic endothelial cells to ONOO-
      significantly increased the phosphorylation of both Thr172 of AMPK and Ser1179 of
      endothelial nitric-oxide synthase, a known downstream enzyme of AMPK. In
      addition, activation of AMPK by ONOO- was accompanied by increased
      phosphorylation of protein kinase Czeta (PKCzeta) (Thr410/403) and translocation
      of cytosolic PKCzeta into the membrane. Further, inhibition of PKCzeta abrogated
      ONOO- -induced AMPK-Thr172 phosphorylation as that of endothelial nitric-oxide
      synthase. Furthermore, overexpression of a constitutively active PKCzeta mutant
      enhanced the phosphorylation of AMPK-Thr172, suggesting that PKCzeta is upstream
      of AMPK activation. In contrast, ONOO- activated PKCzeta in LKB1-deficient HeLa
      S3 but affected neither AMPK-Thr172 nor AMPK activity. These data suggest that
      LKB1 is required for PKCzeta-enhanced AMPK activation. In vitro, recombinant
      PKCzeta phosphorylated LKB1 at Ser428, resulting in phosphorylation of AMPK at
      Thr172. Further, direct mutation of Ser428 of LKB1 into alanine, like the kinase
      inactive LKB1 mutant, abolished ONOO- -induced AMPK activation. In several cell
      types originating from human, rat, and mouse, inhibition of PKCzeta significantly
      attenuated the phosphorylation of both LKB1-Ser428 and AMPK-Thr172 that were
      enhanced by ONOO-. Taken together, we conclude that PKCzeta can regulate AMPK
      activity by increasing the Ser428 phosphorylation of LKB1, resulting in
      association of LKB1 with AMPK and consequent AMPK Thr172 phosphorylation by LKB1.

PMID- 16407221
TI  - Construction, affinity maturation, and biological characterization of an anti
      tumor-associated glycoprotein-72 humanized antibody.
AB  - The tumor-associated glycoprotein (TAG)-72 is expressed in the majority of human
      adenocarcinomas but is rarely expressed in most normal tissues, which makes it a
      potential target for the diagnosis and therapy of a variety of human cancers.
      Here we describe the construction, affinity maturation, and biological
      characterization of an anti-TAG-72 humanized antibody with minimum potential
      immunogenicity. The humanized antibody was constructed by grafting only the
      specificity-determining residues (SDRs) within the complementarity-determining
      regions (CDRs) onto homologous human immunoglobulin germ line segments while
      retaining two mouse heavy chain framework residues that support the conformation
      of the CDRs. The resulting humanized antibody (AKA) showed only about 2-fold
      lower affinity compared with the original murine monoclonal antibody CC49 and 27
      fold lower reactivity to patient serum compared with the humanized antibody
      HuCC49 that was constructed by CDR grafting. The affinity of AKA was improved by
      random mutagenesis of the heavy chain CDR3 (HCDR3). The highest affinity variant
      (3E8) showed 22-fold higher affinity compared with AKA and retained the original
      epitope specificity. Mutational analysis of the HCDR3 residues revealed that the
      replacement of Asn(97) by isoleucine or valine was critical for the affinity
      maturation. The 3E8 labeled with (125)I or (131)I showed efficient tumor
      targeting or therapeutic effects, respectively, in athymic mice with human colon
      carcinoma xenografts, suggesting that 3E8 may be beneficial for the diagnosis and
      therapy of tumors expressing TAG-72.

PMID- 16407222
TI  - Isolated regulatory domains of cGMP-dependent protein kinase Ialpha and Ibeta
      retain dimerization and native cGMP-binding properties and undergo isoform
      specific conformational changes.
AB  - Molecular mechanisms that provide for cGMP activation of cGMP-dependent protein
      kinase (PKG) are unknown. PKGs are dimeric; each monomer contains a regulatory
      (R) and catalytic (C) domain. In this study, isolated recombinant R domains of
      PKGIalpha-(Delta349-670) and PKGIbeta-(Delta364-685) containing the dimerization
      and autoinhibitory subdomains and two allosteric cGMP-binding sites were
      expressed in Sf9 cells. Both R domains were dimers with elongated conformations
      (Stokes radii of 44 and 51 A, respectively, and frictional coefficients of 1.6
      and 1.8, respectively). Exchange dissociation kinetics and K(D) values for cGMP
      were similar for each holoenzyme and its isolated R domain, indicating that under
      these conditions the C domain does not appreciably alter cGMP-binding functions
      of the R domain. As determined by gel filtration chromatography, cGMP binding
      caused elongation of the PKGIalpha-isolated R domain and contraction of the
      PKGIbeta-isolated R domain. Cyclic GMP-bound forms of the isoforms have similar
      physical dimensions that may reflect a common conformation of active isoforms.
      Elongation of the PKGIbeta holoenzyme associated with cGMP binding and PKG
      activation cannot be explained solely by conformational change in its R domain,
      but elongation of the PKGIalpha R domain may partially account for the elongation
      of wild type PKGIalpha associated with cGMP binding. The cGMP-induced
      conformational changes in the respective R domains are likely to be critical for
      kinase activation.

PMID- 16407223
TI  - Protein interaction analysis of ST14 domains and their point and deletion
      mutants.
AB  - ST14 (suppression of tumorigenicity 14) is a transmembrane serine protease that
      contains a serine protease catalytic (SP) domain, an SEA domain, two complement
      subcomponent C1r/s (CUB) domains, and four low density lipoprotein receptor class
      A domains. Glutathione S-transferase fusion proteins with SP, CUB, and low
      density lipoprotein receptor domains and their corresponding mutants were
      generated to analyze protein interactions with these domains. Modified
      glutathione S-transferase pull-down assays demonstrated the interaction between
      the SP domain and hepatocyte growth factor activator inhibitor-1. With the same
      method, a CUB domain-interacting protein was isolated and turned out to be the
      transmembrane protein with epidermal growth factor-like and two follistatin-like
      domains 1 (TMEFF1). Quantitative real time PCR revealed that the expression of
      the TMEFF1 gene was dependent on the transfection of the ST14 gene in the RKO
      cell line. Our results also suggested that ST14 and TMEFF1 were co-expressed in
      the human breast cancer cell line MCF7, human placenta, kidney, and liver
      tissues. Interestingly, these two genes were co-up-regulated in kidney tumors
      versus normal tissues, consistent with our results that showed the dependence of
      TMEFF1 expression on ST14 in RKO cells. Finally, homology modeling studies
      suggested that TMEFF1 might form a complex with ST14 by an interaction between
      epidermal growth factor and CUB domains.

PMID- 16407224
TI  - Control of mitochondrial outer membrane permeabilization and Bcl-xL levels by
      thioredoxin 2 in DT40 cells.
AB  - Mitochondria play a central role in the initiation of apoptosis, which is
      regulated by various factors such as ATP synthesis, reactive oxygen species,
      redox status, and outer membrane permeabilization. Disruption of chicken
      thioredoxin 2 (Trx2), a mitochondrial redox-regulating protein, results in
      apoptosis in DT40 cells. To investigate the mechanism of this apoptosis, we
      prepared transfectants expressing control (DT40-TRX2-/-), human thioredoxin 2
      (TRX2) (DT40-hTRX2), or redox-inactive TRX2 (DT40-hTRX2CS) in conditional Trx2
      deficient DT40 cells containing a tetracycline-repressible Trx2 gene. Production
      of ATP was not significantly changed by down-regulation of Trx2 expression. The
      generation of reactive oxygen species was enhanced by the down-regulation of Trx2
      expression in DT40-TRX2-/-. Unexpectedly, the change was blocked in both DT40
      hTRX2 and DT40-hTRX2CS cells. The down-regulation of Trx2 expression caused the
      release of cytochrome c and apoptosis-inducing factor on day 3, and apoptosis on
      day 5. These changes were also suppressed in both DT40-hTRX2 and DT40-hTRX2CS
      cells, suggesting that TRX2 regulates mitochondrial outer membrane
      permeabilization and apoptosis by redox-active site cysteine-independent
      mechanisms. The down-regulation of Trx2 expression caused a decrease in the
      protein level of Bcl-xL on day 3, whereas the protein level of Bcl-2 did not
      change until day 4, and the mRNA level of Bcl-xL was unchanged. The decrease in
      Bcl-xL was not blocked by a caspase 3 inhibitor but blocked in both DT40-hTRX2
      and DT40-hTRX2CS. These findings indicate a link between the redox active site
      cysteine-independent action of TRX2 and the level of Bcl-xL in the regulation of
      apoptosis.

PMID- 16407225
TI  - Conformational changes associated with receptor-stimulated guanine nucleotide
      exchange in a heterotrimeric G-protein alpha-subunit: NMR analysis of GTPgammaS
      bound states.
AB  - Solution NMR studies of a (15)N-labeled G-protein alpha-subunit (G(alpha))
      chimera ((15)N-ChiT)-reconstituted heterotrimer have shown previously that G
      protein betagamma-subunit (G(betagamma)) association induces a "pre-activated"
      conformation that likely facilitates interaction with the agonist-activated form
      of a G-protein-coupled receptor (R*) and guanine nucleotide exchange (Abdulaev,
      N. G., Ngo, T., Zhang, C., Dinh, A., Brabazon, D. M., Ridge, K. D., and Marino,
      J. P. (2005) J. Biol. Chem. 280, 38071-38080). Here we demonstrated that the
      (15)N-ChiT-reconstituted heterotrimer can form functional complexes under NMR
      experimental conditions with light-activated, detergent-solubilized rhodopsin
      (R*), as well as a soluble mimic of R*. NMR methods were used to track R*
      triggered guanine nucleotide exchange and release of guanosine 5'-O-3
      thiotriphosphate (GTPgammaS)/Mg(2+)-bound ChiT. A heteronuclear single quantum
      correlation (HSQC) spectrum of R*-generated GTPgammaS/Mg(2+)-bound ChiT revealed
      (1)HN, (15)N chemical shift changes relative to GDP/Mg(2+)-bound ChiT that were
      similar, but not identical, to those observed for the GDP.AlF(4)(-)/Mg(2+)-bound
      state. Line widths observed for R*-generated GTPgammaS/Mg(2+)-bound (15)N-ChiT,
      however, indicated that it is more conformationally dynamic relative to the
      GDP/Mg(2+)- and GDP.AlF(4)(-)/Mg(2+)-bound states. The increased dynamics
      appeared to be correlated with G(betagamma) and R* interactions because they are
      not observed for GTPgammaS/Mg(2+)-bound ChiT generated independently of R*. In
      contrast to R*, a soluble mimic that does not catalytically interact with G
      protein (Abdulaev, N. G., Ngo, T., Chen, R., Lu, Z., and Ridge, K. D. (2000) J.
      Biol. Chem. 275, 39354-39363) is found to form a stable complex with the
      GTPgammaS/Mg(2+)-exchanged heterotrimer. The HSQC spectrum of (15)N-ChiT in this
      complex displays a unique chemical shift pattern that nonetheless shares
      similarities with the heterotrimer and GTPgammaS/Mg(2+)-bound ChiT. Overall,
      these results demonstrated that R*-induced changes in G(alpha) can be followed by
      NMR and that guanine nucleotide exchange can be uncoupled from heterotrimer
      dissociation.

PMID- 16407226
TI  - Identification of myxomaviral serpin reactive site loop sequences that regulate
      innate immune responses.
AB  - The thrombolytic serine protease cascade is intricately involved in activation of
      innate immune responses. The urokinase-type plasminogen activator and receptor
      form complexes that aid inflammatory cell invasion at sites of arterial injury.
      Plasminogen activator inhibitor-1 is a mammalian serpin that binds and regulates
      the urokinase receptor complex. Serp-1, a myxomaviral serpin, also targets the
      urokinase receptor, displaying profound anti-inflammatory and anti-atherogenic
      activity in a wide range of animal models. Serp-1 reactive center site mutations,
      mimicking known mammalian and viral serpins, were constructed in order to define
      sequences responsible for regulation of inflammation. Thrombosis, inflammation,
      and plaque growth were assessed after treatment with Serp-1, Serp-1 chimeras,
      plasminogen activator inhibitor-1, or unrelated viral serpins in plasminogen
      activator inhibitor or urokinase receptor-deficient mouse aortic transplants.
      Altering the P1-P1' Arg-Asn sequence compromised Serp-1 protease-inhibitory
      activity and anti-inflammatory activity in animal models; P1-P1' Ala-Ala mutants
      were inactive, P1 Met increased remodeling, and P1' Thr increased thrombosis.
      Substitution of Serp-1 P2-P7 with Ala6 allowed for inhibition of urokinase but
      lost plasmin inhibition, unexpectedly inducing a diametrically opposed,
      proinflammatory response with mononuclear cell activation, thrombosis, and
      aneurysm formation (p < 0.03). Other serpins did not reproduce Serp-1 activity;
      plasminogen activator inhibitor-1 increased thrombosis (p < 0.0001), and
      unrelated viral serpin, CrmA, increased inflammation. Deficiency of urokinase
      receptor in mouse transplants blocked Serp-1 and chimera activity, in some cases
      increasing inflammation. In summary, 1) Serp-1 anti-inflammatory activity is
      highly dependent upon the reactive center loop sequence, and 2) plasmin
      inhibition is central to anti-inflammatory activity.

PMID- 16407227
TI  - Phosphorylation and transactivation of Pax6 by homeodomain-interacting protein
      kinase 2.
AB  - Pax6 is a transcriptional activator that contains two DNA binding domains and a
      potent transcription activation domain in the C terminus, which regulates
      organogenesis of the eye, nose, pancreas, and central nervous system. Homeodomain
      interacting protein kinase 2 (HIPK2) interacts with transcription factors,
      including homeoproteins, and regulates activities of transcription factors. Here
      we show that HIPK2 phosphorylates the activation domain of Pax6, which augments
      Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric
      analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and
      373. The substitutions of these threonines with alanines decreased Pax6
      transactivation, whereas substitutions to glutamic acids increased
      transactivation in mimicry of phosphorylation. Furthermore, the knock-down of
      either endogenous or exogenous HIPK2 expression with HIPK2 shRNA markedly
      inhibited Pax6 phosphorylation and its transactivating function on proglucagon
      promoter in cultured cells. These results strongly indicate that HIPK2 is an
      upstream protein kinase for Pax6 and suggest that it modulates Pax6-mediated
      transcriptional regulation.

PMID- 16407228
TI  - Cyclin-dependent kinase (CDK) inhibitors regulate the CDK-cyclin complex
      activities in endoreduplicating cells of developing tomato fruit.
AB  - The jelly-like locular (gel) tissue of tomato fruit is made up of large thin
      walled and highly vacuolized cells. The development of the gel tissue is
      characterized by the arrest of mitotic activities, the inhibition of cyclin
      dependent kinase A (CDKA) activity, and numerous rounds of nuclear DNA
      endoreduplication. To decipher the molecular determinants controlling these
      developmental events, we investigated the putative involvement of CDK inhibitors
      (p27(Kip)-related proteins, or KRPs) during the endoreduplication process. Two
      cDNAs, LeKRP1 and LeKRP2, encoding tomato CDK inhibitors were isolated. The
      LeKRP1 and LeKRP2 transcript expression was shown to be enhanced in the
      differentiating cells of the gel undergoing endoreduplication. At the
      translational level, LeKRP1 was shown to accumulate in the gel tissue and to
      participate in the inhibition of the CDK-cyclin kinase activities occurring in
      endoreduplicating cells of the gel tissue. We here propose that LeKRP1
      participates in the control of both the cell cycle and the endoreduplication
      cycle.

PMID- 16407229
TI  - The novel WD-repeat protein Morg1 acts as a molecular scaffold for hypoxia
      inducible factor prolyl hydroxylase 3 (PHD3).
AB  - Hypoxia-inducible factor-1 (HIF-1), a transcriptional complex composed of an
      oxygen-sensitive alpha- and a beta-subunit, plays a pivotal role in cellular
      adaptation to low oxygen availability. Under normoxia, the alpha-subunit of HIF-1
      is hydroxylated by a family of prolyl hydroxylases (PHDs) and consequently
      targeted for proteasomal degradation. Three different PHDs have been identified,
      but the difference among their in vivo roles remain unclear. PHD3 is strikingly
      expressed by hypoxia, displays high substrate specificity, and has been
      identified in other signaling pathways. PHD3 may therefore hydroxylate divergent
      substrates and/or connect divergent cellular responses with HIF. We identified a
      novel WD-repeat protein, recently designated Morg1 (MAPK organizer 1), by
      screening a cDNA library with yeast two-hybrid assays. The interaction between
      PHD3 and Morg1 was confirmed in vitro and in vivo. We found seven WD-repeat
      domains by cloning the full-length cDNA of Morg1. By confocal microscopy both
      proteins co-localize within the cytoplasm and the nucleus and display a similar
      tissue expression pattern in Northern blots. Binding occurs at a conserved region
      predicted to the top surface of one propeller blade. Finally, HIF-mediated
      reporter gene activity is decreased by Morg1 and reduced to basal levels when
      Morg1 is co-expressed with PHD3. Suppression of Morg1 or PHD3 by stealth RNA
      leads to a marked increase of HIF-1 activity. These results indicate that Morg1
      specifically interacts with PHD3 most likely by acting as a molecular scaffold.
      This interaction may provide a molecular framework between HIF regulation and
      other signaling pathways.

PMID- 16407230
TI  - Hydrolysis of ATP by aminoglycoside 3'-phosphotransferases: an unexpected cost to
      bacteria for harboring an antibiotic resistance enzyme.
AB  - Aminoglycoside 3'-phosphotransferases (APH(3')s) are common bacterial resistance
      enzymes to aminoglycoside antibiotics. These enzymes transfer the gamma
      phosphoryl group of ATP to the 3'-hydroxyl of the antibiotics, whereby the
      biological activity of the drugs is lost. Pre-steady-state and steady-state
      kinetics with two of these enzymes from Gram-negative bacteria, APH(3')-Ia and
      APH(3')-IIa, were performed. It is demonstrated that these enzymes in both
      ternary and binary complexes facilitate an ATP hydrolase activity (ATPase), which
      is competitive with the transfer of phosphate to the antibiotics. Because these
      enzymes are expressed constitutively in resistant bacteria, the turnover of ATP
      is continuous during the lifetime of the organism both in the absence and the
      presence of aminoglycosides. Concentrations of the enzyme in vivo were
      determined, and it was estimated that in a single generation of bacterial growth
      there exists the potential that this activity would consume as much as
      severalfold of the total existing ATP. Studies with bacteria harboring the
      aph(3')-Ia gene revealed that bacteria are able to absorb the cost of this ATP
      turnover, as ATP is recycled. However, the cost burden of this adventitious
      activity manifests a selection pressure against maintenance of the plasmids that
      harbor the aph(3')-Ia gene, such that approximately 50% of the plasmid is lost in
      1500 bacterial generations in the absence of antibiotics. The implication is
      that, in the absence of selection, bacteria harboring an enzyme that catalyzes
      the consumption of key metabolites could experience the loss of the plasmid that
      encodes for the given enzyme.

PMID- 16407231
TI  - Common determinants of single channel conductance within the large cytoplasmic
      loop of 5-hydroxytryptamine type 3 and alpha4beta2 nicotinic acetylcholine
      receptors.
AB  - Homomeric 5-hydroxytryptamine type 3A receptors (5-HT3ARs) have a single channel
      conductance (gamma) below the resolution of single channel recording (966 +/- 75
      fS, estimated by variance analysis). By contrast, heteromeric 5-HT3A/B and
      nicotinic acetylcholine receptors (nAChRs) have picosiemen range gamma values. In
      this study, single channel recordings revealed that replacement of cytoplasmic
      membrane-associated (MA) helix arginine 432 (-4'), 436 (0'), and 440 (4')
      residues by 5-HT3B (-4'Gln, 0'Asp, and 4'Ala) residues increases gamma to 36.5 +/
      1.0 pS. The 0' residue makes the most substantial contribution to gamma of the 5
      HT3AR. Replacement of 0'Arg by aspartate, glutamate (alpha7 nAChR subunit MA 0'),
      or glutamine (beta2 subunit MA 0') increases gamma to the resolvable range (>6
      pS). By contrast, replacement of 0'Arg by phenylalanine (alpha4 subunit MA 0')
      reduced gamma to 416 +/- 107 fS. In reciprocal experiments with alpha4beta2
      nAChRs (gamma = 31.3 +/- 0.8 pS), replacement of MA 0' residues by arginine in
      alpha4beta2(Q443R) and alpha4(F588R)beta2 reduced gamma slightly. By contrast,
      the gamma of double mutant alpha4(F588R)beta2(Q443R) was halved. The MA -4' and
      4' residues also influenced gamma of 5-HT3ARs. Replacement of nAChR alpha4 or
      beta2 MA 4' residues by arginine made current density negligible. By contrast,
      replacement of both -4' residues by arginine produced functional nAChRs with
      substantially reduced gamma (11.4 +/- 0.5 pS). Homology models of the 5-HT3A and
      alpha4beta2 nAChRs against Torpedo nAChR revealed MA -4', 0', and 4' residues
      within five intracellular portals. This locus may be a common determinant of ion
      conduction throughout the Cys loop receptor family.

PMID- 16407232
TI  - Latent nitrate transport activity of a novel sulfate permease-like protein of the
      cyanobacterium Synechococcus elongatus.
AB  - The Synechococcus elongatus mutant lacking the nrtABCD gene cluster (NA3) is
      defective in active nitrate transport and requires high nitrate concentrations
      (>30 mm) for sustained growth. Prolonged incubation of NA3 in medium containing 2
      mm nitrate led to isolation of a pseudorevertant (NA3R) capable of transport of
      millimolar concentrations of nitrate, from which three mutants with improved
      affinity for nitrate were obtained. We identified three genes responsible for the
      latent transport activity for nitrate: ltnA, which encodes a response regulator
      with no effector domain; ltnB, which encodes a hybrid histidine kinase with two
      receiver domains; and ltnT, which encodes a sulfate permease-like protein with a
      putative cyclic nucleoside monophosphate (cNMP)-binding domain. Missense
      mutations of the high affinity derivatives of NA3R were found in ltnT, verifying
      that LtnT acts as the transporter. Overexpression of truncated LtnT lacking the
      cNMP-binding domain (but not full-length LtnT) conferred nitrate transport
      activity on NA3, suggesting that the cNMP-binding domain inhibits transport under
      normal conditions. A nonsense mutation in ltnB that resulted in elimination of
      the receiver domains of the encoded protein was responsible for expression of
      nitrate transport activity in NA3R. Expression of LtnB derivatives lacking the
      receiver domains also conferred low affinity nitrate transport activity on NA3.
      The phosphoryl group of the histidine kinase domain of LtnB was transferred to
      Asp(52) of LtnA in vitro. Overexpression of LtnA (but not LtnA(D52E)) led to
      manifestation of the latent nitrate transport activity in NA3, indicating
      involvement of phosphorylated LtnA in activation of the novel transporter.

PMID- 16407233
TI  - Serum opacity factor, a streptococcal virulence factor that binds to
      apolipoproteins A-I and A-II and disrupts high density lipoprotein structure.
AB  - Serum opacity factor (SOF) is a virulence determinant of group A streptococci
      that opacifies mammalian sera. We analyzed the specificity and mechanism of the
      opacity reaction using a recombinant form of the amino-terminal opacification
      domain of SOF, rSOF. Our data indicate that rSOF is neither a protease nor a
      lipase, but rather it is the binding of rSOF to high density lipoprotein (HDL)
      that triggers the opacity reaction. rSOF did not opacify plasma from apoA-I(-/-)
      mice or purified low or very low density lipoproteins but readily opacified HDL.
      rSOF binding to HDL was characterized by two high affinity binding sites; it
      bound to apoA-I (K(d) = 6 nm) and apoA-II (K(d) = 30 nm), and both apoA-I and
      apoA-II blocked the binding of rSOF to HDL. Electron microscopic examination and
      biochemical analyses of HDL treated with rSOF revealed the formation of lipid
      droplets devoid of apolipoproteins. Thus, SOF interacts with HDL in human blood
      by binding to apoA-I and apoA-II and causing the release of HDL lipid cargo,
      which coalesces to form lipid droplets, resulting in opacification. The
      disruption of HDL may attenuate its anti-inflammatory functions and contribute to
      the pathogenesis of group A streptococcal infections.

PMID- 16407235
TI  - Mouse sperm lacking ADAM1b/ADAM2 fertilin can fuse with the egg plasma membrane
      and effect fertilization.
AB  - Fertilin, a heterodimeric protein complex composed of alpha (ADAM1) and beta
      (ADAM2) subunits on the sperm surface, is believed to mediate adhesion and fusion
      between the sperm and egg plasma membranes. Here we have shown that mutant male
      mice lacking ADAM1b are fertile and that the loss of ADAM1b results in no
      significant defect in sperm functions such as migration from the uterus into
      oviduct, binding to egg zona pellucida, and fusion with zona pellucida-free eggs.
      ADAM1b-deficient epididymal sperm showed a severe reduction of ADAM2 on the cell
      surface, despite the normal presence of ADAM2 in testicular germ cells. The
      appearance of ADAM1b and ADAM2 on the sperm surface depended on formation and
      abundance of ADAM1b/ADAM2 fertilin in testicular germ cells. These results
      suggest that mouse ADAM1b/ADAM2 fertilin may play a crucial role not in the
      sperm/egg fusion but in the appearance of these two ADAMs on the sperm surface.

PMID- 16407234
TI  - Herpes simplex virus disrupts NF-kappaB regulation by blocking its recruitment on
      the IkappaBalpha promoter and directing the factor on viral genes.
AB  - Herpes simplex viruses (HSVs) are able to hijack the host-cell IkappaB kinase
      (IKK)/NF-kappaB pathway, which regulates critical cell functions from apoptosis
      to inflammatory responses; however, the molecular mechanisms involved and the
      outcome of the signaling dysregulation on the host-virus interaction are mostly
      unknown. Here we show that in human keratinocytes HSV-1 attains a sophisticated
      control of the IKK/NF-kappaB pathway, inducing two distinct temporally controlled
      waves of IKK activity and disrupting the NF-kappaB autoregulatory mechanism.
      Using chromatin immunoprecipitation we demonstrate that dysregulation of the NF
      kappaB-response is mediated by a virus-induced block of NF-kappaB recruitment to
      the promoter of the IkappaBalpha gene, encoding the main NF-kappaB-inhibitor. We
      also show that HSV-1 redirects NF-kappaB recruitment to the promoter of ICP0, an
      immediate-early viral gene with a key role in promoting virus replication. The
      results reveal a new level of control of cellular functions by invading viruses
      and suggest that persistent NF-kappaB activation in HSV-1-infected cells, rather
      than being a host response to the virus, may play a positive role in promoting
      efficient viral replication.

PMID- 16407236
TI  - Myospryn is a direct transcriptional target for MEF2A that encodes a striated
      muscle, alpha-actinin-interacting, costamere-localized protein.
AB  - The full repertoire of proteins that comprise the striated muscle Z-disc and
      peripheral structures, such as the costamere, have yet to be discovered. Recent
      studies suggest that this elaborate protein network, which acts as a structural
      and signaling center for striated muscle, harbors factors that function as
      mechanosensors to ensure coordinated contractile activity. Mutations in genes
      whose products reside in this region often result in skeletal and cardio
      myopathies, demonstrating the importance of this macromolecular complex in muscle
      structure and function. Here, we describe the characterization of a direct,
      downstream target gene for the MEF2A transcription factor encoding a large,
      muscle-specific protein that localizes to the costamere in striated muscle. This
      gene, called myospryn, was identified by microarray analysis as a transcript down
      regulated in MEF2A knock-out mice. MEF2A knock-out mice develop cardiac failure
      during the perinatal period with mutant hearts exhibiting several cardiac
      abnormalities including myofibrillar disarray. Myospryn is the mouse ortholog of
      a partial human cDNA of unknown function named cardiomyopathy-associated gene 5
      (CMYA5). Myospryn is expressed as a single, large transcript of approximately 12
      kilobases in adult heart and skeletal muscle with an open reading frame of 3739
      amino acids. This protein, belonging to the tripartite motif superfamily of
      proteins, contains a B-box coiled-coil (BBC), two fibronectin type III (FN3)
      repeats, and SPRY domains and interacts with the sarcomeric Z-disc protein, alpha
      actinin-2. Our findings demonstrate that myospryn functions directly downstream
      of MEF2A at the costamere in striated muscle potentially playing a role in
      myofibrillogenesis.

PMID- 16407237
TI  - NMR structure of the R-module: a parallel beta-roll subunit from an Azotobacter
      vinelandii mannuronan C-5 epimerase.
AB  - In the bacterium Azotobacter vinelandii, a family of seven secreted and calcium
      dependent mannuronan C-5 epimerases (AlgE1-7) has been identified. These
      epimerases are responsible for the epimerization of beta-d-mannuronic acid to
      alpha-l-guluronic acid in alginate polymers. The epimerases consist of two types
      of structural modules, designated A (one or two copies) and R (one to seven
      copies). The structure of the catalytically active A-module from the smallest
      epimerase AlgE4 (consisting of AR) has been solved recently. This paper describes
      the NMR structure of the R-module from AlgE4 and its titration with a substrate
      analogue and paramagnetic thulium ions. The R-module folds into a right-handed
      parallel beta-roll. The overall shape of the R-module is an elongated molecule
      with a positively charged patch that interacts with the substrate. Titration of
      the R-module with thulium indicated possible calcium binding sites in the loops
      formed by the nonarepeat sequences in the N-terminal part of the molecule and the
      importance of calcium binding for the stability of the R-module. Structure
      calculations showed that calcium ions can be incorporated in these loops without
      structural violations and changes. Based on the structure and the electrostatic
      surface potential of both the A- and R-module from AlgE4, a model for the
      appearance of the whole protein is proposed.

PMID- 16407238
TI  - Calorimetric analysis of thermodynamic stability and aggregation for apo and holo
      amyotrophic lateral sclerosis-associated Gly-93 mutants of superoxide dismutase.
AB  - Differential scanning calorimetry was used to measure changes in thermodynamic
      stability and aggregation for glycine 93 mutants of human copper, zinc-superoxide
      dismutase (SOD). Glycine 93 is a conserved residue at position i + 3 of a tight
      turn and has been found to be a mutational hot spot in familial amyotrophic
      lateral sclerosis (fALS). The fALS-associated mutations, G93A, G93S, G93R, G93D,
      and G93V, were made in a pseudo wild-type background containing no free
      cysteines, which prevented the formation of aberrant disulfide bonds upon thermal
      unfolding, and enabled quantitative thermodynamic analysis of the effects of the
      mutations. Thermal unfolding was highly reversible for all the SODs in both the
      fully metallated (holo) and metal-free (apo) forms. The data for all the holo
      SODs and for the apo-pseudo-wild-type SOD were well fit by a 2-state unfolding
      model for native dimer (N2) to two unfolded monomers (2U), N2 <--> 2U. The holo-
      and apo-forms of the mutants are significantly destabilized (by 1.5-3.5 kcal mol(
      1) monomer) relative to the corresponding forms of pseudo wild-type, with the
      relative stabilities being correlated with statistical preferences for amino
      acids in this structural context. Although van't Hoff (DeltaHvH) to calorimetric
      (DeltaHcal) enthalpy ratios are close to unity for all the holo-SODs and for apo
      pseudo-wild-type, consistent with a 2-state transition, DeltaHvH is considerably
      larger than DeltaHcal for all the apo-mutants. This suggests that the mutations
      cause apo-SOD to have an increased propensity to misfold or aggregate, which may
      be linked to increased toxic mutant SOD aggregation in fALS.

PMID- 16407239
TI  - Inducible phosphorylation of NF-kappa B p65 at serine 468 by T cell costimulation
      is mediated by IKK epsilon.
AB  - Here we identify IKKepsilon as a novel NF-kappaB p65 kinase that mediates
      inducible phosphorylation of Ser468 and Ser536 in response to T cell
      costimulation. In addition, the kinase activity of IKKepsilon contributes to the
      control of p65 nuclear uptake. Serines 468 and 536 are evolutionarily conserved,
      and the surrounding amino acids display sequence homology. Down-regulation of
      IKKepsilon levels by small interfering RNA does not affect inducible
      phosphorylation of Ser536 but largely prevents Ser468 phosphorylation induced by
      T cell costimulation. Ser536-phosphorylated p65 is found predominantly in the
      cytosol. In contrast, the Ser468 phosphorylated form of this transcription factor
      occurs mainly in the nucleus, suggesting a function for transactivation.
      Reconstitution of p65-/- cells with either wild type p65 or point-mutated p65
      variants showed that inducible phosphorylation of Ser468 serves to enhance p65
      dependent transactivation. These results also provide a mechanistic link that
      helps to explain the relevance of IKKepsilon for the expression of a subset of NF
      kappaB target genes without affecting cytosolic IkappaBalpha degradation.

PMID- 16407240
TI  - The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor
      phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties.
AB  - The glutamic acid-rich protein-2 (GARP2) is a splice variant of the beta-subunit
      of the cGMP-gated ion channel of rod photoreceptors. GARP2 is believed to
      interact with several membrane-associated phototransduction proteins in rod
      photoreceptors. In this study, we demonstrated that GARP2 is a high affinity PDE6
      binding protein and that PDE6 co-purifies with GARP2 during several stages of
      chromatographic purification. We found that hydrophobic interaction
      chromatography succeeds in quantitatively separating GARP2 from the PDE6
      holoenzyme. Furthermore, the 17-kDa prenyl-binding protein, abundant in retinal
      cells, selectively released PDE6 (but not GARP2) from rod outer segment
      membranes, demonstrating the specificity of the interaction between GARP2 and
      PDE6. Purified GARP2 was able to suppress 80% of the basal activity of the
      nonactivated, membrane-bound PDE6 holoenzyme at concentrations equivalent to its
      endogenous concentration in rod outer segment membranes. However, GARP2 was
      unable to reverse the transducin activation of PDE6 (in contrast to a previous
      study) nor did it significantly alter catalysis of the fully activated PDE6
      catalytic dimer. The high binding affinity of GARP2 for PDE6 and its ability to
      regulate PDE6 activity in its dark-adapted state suggest a novel role for GARP2
      as a regulator of spontaneous activation of rod PDE6, thereby serving to lower
      rod photoreceptor "dark noise" and allowing these sensory cells to operate at the
      single photon detection limit.

PMID- 16407242
TI  - An evolutionarily conserved function of proliferating cell nuclear antigen for
      Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage.
AB  - The DNA replication licensing factor Cdt1 is degraded by the ubiquitin-proteasome
      pathway during S phase of the cell cycle, to ensure one round of DNA replication
      during each cell division and in response to DNA damage to halt DNA replication.
      Constitutive expression of Cdt1 causes DNA re-replication and is associated with
      the development of a subset of human non-small cell-lung carcinomas. In mammalian
      cells, DNA damage-induced Cdt1 degradation is catalyzed by the Cul4-Ddb1-Roc1 E3
      ubiquitin ligase. We report here that overexpression of the proliferating cell
      nuclear antigen (PCNA) inhibitory domain from the CDK inhibitors p21 and p57, but
      not the CDK-cyclin inhibitory domain, blocked Cdt1 degradation in cultured
      mammalian cells after UV irradiation. In vivo soluble Cdt1 and PCNA co-elute by
      gel filtration and associate with each other physically. Silencing PCNA in
      cultured mammalian cells or repression of pcn1 expression in fission yeast
      blocked Cdt1 degradation in response to DNA damage. Unexpectedly, deletion of
      Ddb1 in fission yeast cells also accumulated Cdt1 in the absence of DNA damage.
      We suggest that the Cul4-Ddb1 ligase evolved to ubiquitinate Cdt1 during normal
      cell growth as well as in response to DNA damage and a separate E3 ligase,
      possibly SCF(Skp2), evolved to either share or take over the function of Cdt1
      ubiquitination during normal cell growth and that PCNA is involved in mediating
      Cdt1 degradation by the Cul4-Ddb1 ligase in response to DNA damage.

PMID- 16407241
TI  - Role of the G protein-coupled receptor kinase site serine cluster in beta2
      adrenergic receptor internalization, desensitization, and beta-arrestin
      translocation.
AB  - There is considerable evidence for the role of carboxyl-terminal serines 355,
      356, and 364 in G protein-coupled receptor kinase (GRK)-mediated phosphorylation
      and desensitization of beta(2)-adrenergic receptors (beta(2)ARs). In this study
      we used receptors in which these serines were changed to alanines (SA3) or to
      aspartic acids (SD3) to determine the role of these sites in beta-arrestin
      dependent beta(2)AR internalization and desensitization. Coupling efficiencies
      for epinephrine activation of adenylyl cyclase were similar in wild-type and
      mutant receptors, demonstrating that the SD3 mutant did not drive constitutive
      GRK desensitization. Treatment of wild-type and mutant receptors with 0.3 nm
      isoproterenol for 5 min induced approximately 2-fold increases in the EC(50) for
      agonist activation of adenylyl cyclase, consistent with protein kinase A (PKA)
      site-mediated desensitization. When exposed to 1 mum isoproterenol to trigger GRK
      site-mediated desensitization, only wild-type receptors showed significant
      further desensitization. Using a phospho site-specific antibody, we determined
      that there is no requirement for these GRK sites in PKA-mediated phosphorylation
      at high agonist concentration. The rates of agonist-induced internalization of
      the SD3 and SA3 mutants were 44 and 13%, respectively, relative to that of wild
      type receptors, but the SD3 mutant recruited enhanced green fluorescent protein
      (EGFP)-beta-arrestin 2 to the plasma membrane, whereas the SA3 mutant did not.
      EGFP-beta-Arrestin2 overexpression triggered a significant increase in the extent
      of SD3 mutant desensitization but had no effect on the desensitization of wild
      type receptors or the SA3 mutant. Expression of a phosphorylation-independent
      beta-arrestin 1 mutant (R169E) significantly rescued the internalization defect
      of the SA3 mutant but inhibited the phosphorylation of serines 355 and 356 in
      wild-type receptors. Our data demonstrate that (i) the lack of GRK sites does not
      impair PKA site phosphorylation, (ii) the SD3 mutation inhibits GRK-mediated
      desensitization although it supports some agonist-induced beta-arrestin binding
      and receptor internalization, and (iii) serines 355, 356, and 364 play a pivotal
      role in the GRK-mediated desensitization, beta-arrestin binding, and
      internalization of beta(2)ARs.

PMID- 16407243
TI  - The inflammatory mediator leukotriene D4 induces beta-catenin signaling and its
      association with antiapoptotic Bcl-2 in intestinal epithelial cells.
AB  - Increased levels of the inflammatory mediator leukotriene D4 (LTD4) are present
      at sites of inflammatory bowel disease, and such areas also exhibit an increased
      risk for subsequent cancer development. It is known that LTD4 affects the
      expression of many proteins that influence survival and proliferation of
      intestinal epithelial cells. We demonstrate here that after LTD4 exposure, beta
      catenin translocates to the nucleus where it signals activation of the TCF/LEF
      family of transcription factors. These events are mediated via a
      phosphatidylinositol 3-kinase-dependent phosphorylation of the inhibitory Ser-9
      residue of glycogen synthase kinase 3beta. We also show that in the presence of
      LTD4, free beta-catenin translocates to the mitochondria where it associates with
      the cell survival protein Bcl-2. We hypothesize that LTD4 may enhance cell
      survival via activation of beta-catenin signaling, in particular, by promoting
      the association of beta-catenin with Bcl-2 in the mitochondria. Similar to Wnt-1
      signaling, LTD4 signals an increased level of free beta-catenin and elevated
      TCF/LEF promotor activity. This work in intestinal epithelial cells further lends
      credence to the idea that inflammatory signaling pathways are intrinsically
      linked with potential oncogenic signals involved in cell survival and apoptosis.

PMID- 16407244
TI  - Non-cytotoxic cobra cardiotoxin A5 binds to alpha(v)beta3 integrin and inhibits
      bone resorption. Identification of cardiotoxins as non-RGD integrin-binding
      proteins of the Ly-6 family.
AB  - Severe tissue necrosis with a retarded wound healing process is a major symptom
      of a cobra snakebite. Cardiotoxins (CTXs) are major components of cobra venoms
      that belong to the Ly-6 protein family and are implicated in tissue damage. The
      interaction of the major CTX from Taiwan cobra, i.e. CTX A3, with sulfatides in
      the cell membrane has recently been shown to induce pore formation and cell
      internalization and to be responsible for cytotoxicity in cardiomyocytes (Wang,
      C.-H., Liu, J.-H., Lee, S.-C., Hsiao, C.-D., and Wu, W.-g. (2006) J. Biol. Chem.
      281, 656-667). We show here that one of the non-cytotoxic CTXs, i.e. CTX A5 or
      cardiotoxin-like basic polypeptide, from Taiwan cobra specifically bound to
      alpha(v)beta3 integrin and inhibited bone resorption activity. We found that both
      membrane-bound and recombinant soluble alpha(v)beta3 integrins bound specifically
      to CTX A5 in a dose-dependent manner. Surface plasmon resonance analysis showed
      that human soluble alpha(v)beta3 bound to CTX A5 with an apparent affinity of
      approximately 0.3 microM. Calf pulmonary artery endothelial cells, which
      constitutively express alpha(v)beta3, showed a CTX A5 binding profile similar to
      that of membrane-bound and soluble alpha(v)beta3 integrins, suggesting that
      endothelial cells are a potential target for CTX action. We tested whether CTX A5
      inhibits osteoclast differentiation and bone resorption, a process known to be
      involved in alpha(v)beta3 binding and inhibited by RGD-containing peptides. We
      demonstrate that CTX A5 inhibited both activities at a micromolar range by
      binding to murine alpha(v)beta3 integrin in osteoclasts and that CTX A5 co
      localized with beta3 integrin. Finally, after comparing the integrin binding
      affinity among CTX homologs, we propose that the amino acid residues near the two
      loops of CTX A5 are involved in integrin binding. These results identify CTX A5
      as a non-RGD integrin-binding protein with therapeutic potential as an integrin
      antagonist.

PMID- 16407245
TI  - Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and
      memory.
AB  - Plasma membrane Na+/Ca2+-exchangers play a predominant role in Ca2+ extrusion in
      brain. Neurons express several different Na+/Ca2+-exchangers belonging to both
      the K+-independent NCX family and the K+-dependent NCKX family. The unique
      contributions of each of these proteins to neuronal Ca2+ homeostasis and/or
      physiology remain largely unexplored. To address this question, we generated mice
      in which the gene encoding the abundant neuronal K+ -dependent Na+/Ca2+-exchanger
      protein, NCKX2, was knocked out. Analysis of these animals revealed a significant
      reduction in Ca2+ flux in cortical neurons, a profound loss of long term
      potentiation and an increase in long term depression at hippocampal Schaffer/CA1
      synapses, and clear deficits in specific tests of motor learning and spatial
      working memory. Surprisingly, there was no obvious loss of photoreceptor function
      in cones, where expression of the NCKX2 protein had been reported previously.
      These data emphasize the critical and non-redundant role of NCKX2 in the local
      control of neuronal [Ca2+] that is essential for the development of synaptic
      plasticity associated with learning and memory.

PMID- 16407246
TI  - Fyn is required for haloperidol-induced catalepsy in mice.
AB  - Fyn-mediated tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) receptor
      subunits has been implicated in various brain functions, including ethanol
      tolerance, learning, and seizure susceptibility. In this study, we explored the
      role of Fyn in haloperidol-induced catalepsy, an animal model of the
      extrapyramidal side effects of antipsychotics. Haloperidol induced catalepsy and
      muscle rigidity in the control mice, but these responses were significantly
      reduced in Fyn-deficient mice. Expression of the striatal dopamine D(2) receptor,
      the main site of haloperidol action, did not differ between the two genotypes.
      Fyn activation and enhanced tyrosine phosphorylation of the NMDA receptor NR2B
      subunit, as measured by Western blotting, were induced after haloperidol
      injection of the control mice, but both responses were significantly reduced in
      Fyn-deficient mice. Dopamine D(2) receptor blockade was shown to increase both
      NR2B phosphorylation and the NMDA-induced calcium responses in control cultured
      striatal neurons but not in Fyn-deficient neurons. Based on these findings, we
      proposed a new molecular mechanism underlying haloperidol-induced catalepsy, in
      which the dopamine D(2) receptor antagonist induces striatal Fyn activation and
      the subsequent tyrosine phosphorylation of NR2B alters striatal neuronal
      activity, thereby inducing the behavioral changes that are manifested as a
      cataleptic response.

PMID- 16407247
TI  - Purification, kinetic characterization, and mapping of the minimal catalytic
      domain and the key polar groups of Helicobacter pylori alpha-(1,3/1,4)
      fucosyltransferases.
AB  - The minimal catalytic domain of alpha-(1,3/1,4)-fucosyltransferases (FucTs) from
      Helicobacter pylori strains NCTC11639 and UA948 was mapped by N- and C-terminal
      truncations. Only the C terminus could be truncated without significant loss of
      activity. 11639FucT and UA948FucT contain 10 and 8 heptad repeats, respectively,
      which connect the catalytic domain with the C-terminal putative amphipathic alpha
      helices. Deletion of all heptad repeats almost completely abolished enzyme
      activity. Nevertheless, with only one heptad repeat 11639FucT is fully active,
      whereas UA948FucT is partially active. Removal of the two putative amphipathic
      alpha-helices dramatically increased protein expression and solubility, enabling
      purification with yields of milligrams/liter. Steady-state kinetic analysis of
      the purified FucTs showed that 11639FucTs possessed slightly tighter binding
      affinity for both Type II acceptor and GDP-fucose donor than UA948FucT, and its
      kcat of 2.3 s(-1) was double that of UA948FucT, which had a kcat value of 1.1 s(
      1) for both Type II and Type I acceptors. UA948FucT strongly favors Type II over
      the Type I acceptor with a 20-fold difference in acceptor Km. Sixteen modified
      Type I and Type II series acceptors were employed to map the molecular
      determinants of acceptors required for recognition by H. pylori alpha-(1,3/1,4)
      FucTs. Deoxygenation at 6-C of the galactose in Type II acceptor caused a 5000
      fold decrease in alpha1,3 activity, whereas in Type I acceptor this completely
      abolished alpha1,4 activity, indicating that this hydroxyl group is a key polar
      group.

PMID- 16407248
TI  - The structure of beta-carbonic anhydrase from the carboxysomal shell reveals a
      distinct subclass with one active site for the price of two.
AB  - CsoSCA (formerly CsoS3) is a bacterial carbonic anhydrase localized in the shell
      of a cellular microcompartment called the carboxysome, where it converts HCO(3)(
      ) to CO(2) for use in carbon fixation by ribulose-bisphosphate
      carboxylase/oxygenase (RuBisCO). CsoSCA lacks significant sequence similarity to
      any of the four known classes of carbonic anhydrase (alpha, beta, gamma, or
      delta), and so it was initially classified as belonging to a new class, epsilon.
      The crystal structure of CsoSCA from Halothiobacillus neapolitanus reveals that
      it is actually a representative member of a new subclass of beta-carbonic
      anhydrases, distinguished by a lack of active site pairing. Whereas a typical
      beta-carbonic anhydrase maintains a pair of active sites organized within a two
      fold symmetric homodimer or pair of fused, homologous domains, the two domains in
      CsoSCA have diverged to the point that only one domain in the pair retains a
      viable active site. We suggest that this defunct and somewhat diminished domain
      has evolved a new function, specific to its carboxysomal environment. Despite the
      level of sequence divergence that separates CsoSCA from the other two subclasses
      of beta-carbonic anhydrases, there is a remarkable level of structural similarity
      among active site regions, which suggests a common catalytic mechanism for the
      interconversion of HCO(3)(-) and CO(2). Crystal packing analysis suggests that
      CsoSCA exists within the carboxysome shell either as a homodimer or as extended
      filaments.

PMID- 16407249
TI  - Calcium-induced acrosomal exocytosis requires cAMP acting through a protein
      kinase A-independent, Epac-mediated pathway.
AB  - Epac, a guanine nucleotide exchange factor for the small GTPase Rap, binds to and
      is activated by the second messenger cAMP. In sperm, there are a number of
      signaling pathways required to achieve egg-fertilizing ability that depend upon
      an intracellular rise of cAMP. Most of these processes were thought to be
      mediated by cAMP-dependent protein kinases. Here we report a new dependence for
      the cAMP-induced acrosome reaction involving Epac. The acrosome reaction is a
      specialized type of regulated exocytosis leading to a massive fusion between the
      outer acrosomal and the plasma membranes of sperm cells. Ca2+ is the archetypical
      trigger of regulated exocytosis, and we show here that its effects on acrosomal
      release are fully mediated by cAMP. Ca2+ failed to trigger acrosomal exocytosis
      when intracellular cAMP was depleted by an exogenously added phosphodiesterase or
      when Epac was sequestered by specific blocking antibodies. The nondiscriminating
      dibutyryl-cAMP and the Epac-selective 8-(p-chlorophenylthio)-2'-O-methyladenosine
      3',5'-cyclic monophosphate analogues triggered the acrosome reaction in the
      effective absence of extracellular Ca2+. This indicates that cAMP, via Epac
      activation, has the ability to drive the whole cascade of events necessary to
      bring exocytosis to completion, including tethering and docking of the acrosome
      to the plasma membrane, priming of the fusion machinery, mobilization of
      intravesicular Ca2+, and ultimately, bilayer mixing and fusion. cAMP-elicited
      exocytosis was sensitive to anti-alpha-SNAP, anti-NSF, and anti-Rab3A antibodies,
      to intra-acrosomal Ca2+ chelators, and to botulinum toxins but was resistant to
      cAMP-dependent protein kinase blockers. These experiments thus identify Epac in
      human sperm and evince its indispensable role downstream of Ca2+ in exocytosis.

PMID- 16407250
TI  - Functional characterization of the Hansenula polymorpha HOC1, OCH1, and OCR1
      genes as members of the yeast OCH1 mannosyltransferase family involved in protein
      glycosylation.
AB  - The alpha-1,6-mannosyltransferase encoded by Saccharomyces cerevisiae OCH1
      (ScOCH1) is responsible for the outer chain initiation of N-linked
      oligosaccharides. To identify the genes involved in the first step of outer chain
      biosynthesis in the methylotrophic yeast Hansenula polymorpha, we undertook the
      functional analysis of three H. polymorpha genes, HpHOC1, HpOCH1, and HpOCR1,
      that belong to the OCH1 family containing seven members with significant sequence
      identities to ScOCH1. The deletions of these H. polymorpha genes individually
      resulted in several phenotypes suggestive of cell wall defects. Whereas the
      deletion of HpHOC1 (Hphoc1Delta) did not generate any detectable changes in N
      glycosylation, the null mutant strains of HpOCH1 (Hpoch1Delta) and HpOCR1
      (Hpocr1Delta) displayed a remarkable reduction in hypermannosylation. Although
      the apparent phenotypes of Hpocr1Delta were most similar to those of S.
      cerevisiae och1 mutants, the detailed structural analysis of N-glycans revealed
      that the major defect of Hpocr1Delta is not in the initiation step but rather in
      the subsequent step of outer chain elongation by alpha-1,2-mannose addition. Most
      interestingly, Hpocr1Delta showed a severe defect in the O-linked glycosylation
      of extracellular chitinase, representing HpOCR1 as a novel member of the OCH1
      family implicated in both N- and O-linked glycosylation. In contrast, addition of
      the first alpha-1,6-mannose residue onto the core oligosaccharide Man8GlcNAc2 was
      completely blocked in Hpoch1Delta despite the comparable growth of its wild type
      under normal growth conditions. The complementation of the S. cerevisiae och1
      null mutation by the expression of HpOCH1 and the lack of in vitro alpha-1,6
      mannosyltransferase activity in Hpoch1Delta provided supportive evidence that
      HpOCH1 is the functional orthologue of ScOCH1. The engineered Hpoch1Delta strain
      with the targeted expression of Aspergillus saitoi alpha-1,2-mannosidase in the
      endoplasmic reticulum was shown to produce human-compatible high mannose-type
      Man5GlcNAc2 oligosaccharide as a major N-glycan.

PMID- 16407251
TI  - Proliferating human cells hypomorphic for origin recognition complex 2 and pre
      replicative complex formation have a defect in p53 activation and Cdk2 kinase
      activation.
AB  - The Origin Recognition Complex (ORC) is a critical component of replication
      initiation. We have previously reported generation of an Orc2 hypomorph cell line
      (Delta/-) that expresses very low levels of Orc2 but is viable. We have shown
      here that Chk2 is phosphorylated, suggesting that DNA damage checkpoint pathways
      are activated. p53 was inactivated during the derivation of the Orc2 hypomorphic
      cell lines, accounting for their survival despite active Chk2. These cells also
      show a defect in the G1 to S-phase transition. Cdk2 kinase activation in G1 is
      decreased due to decreased Cyclin E levels, preventing progression into S-phase.
      Molecular combing of bromodeoxyuridine-labeled DNA revealed that once the Orc2
      hypomorphic cells enter S-phase, fork density and fork progression are
      approximately comparable with wild type cells. Therefore, the low level of Orc2
      hinders normal cell cycle progression by delaying the activation of G1 cyclin
      dependent kinases. The results suggest that hypomorphic mutations in initiation
      factor genes may be particularly deleterious in cancers with mutant p53 or
      increased activity of Cyclin E/Cdk2.

PMID- 16407252
TI  - PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal
      ubiquitination.
AB  - Cdt1, a protein essential in G1 for licensing of origins for DNA replication, is
      inhibited in S-phase, both by binding to geminin and degradation by proteasomes.
      Cdt1 is also degraded after DNA damage to stop licensing of new origins until
      after DNA repair. Phosphorylation of Cdt1 by cyclin-dependent kinases promotes
      its binding to SCF-Skp2 E3 ubiquitin ligase, but the Cdk2/Skp2-mediated pathway
      is not essential for the degradation of Cdt1. Here we show that the N terminus of
      Cdt1 contains a second degradation signal that is active after DNA damage and in
      S-phase and is dependent on the interaction of Cdt1 with proliferating cell
      nuclear antigen (PCNA) through a PCNA binding motif. The degradation involves N
      terminal ubiquitination and requires Cul4 and Ddb1 proteins, components of an E3
      ubiquitin ligase implicated in protein degradation after DNA damage. Therefore
      PCNA, the matchmaker for many proteins involved in DNA and chromatin metabolism,
      also serves to promote the targeted degradation of associated proteins in S-phase
      or after DNA damage.

PMID- 16407253
TI  - Site-directed mutations of T4 helicase loading protein (gp59) reveal multiple
      modes of DNA polymerase inhibition and the mechanism of unlocking by gp41
      helicase.
AB  - The T4 helicase loading protein (gp59) interacts with a multitude of DNA
      replication proteins. In an effort to determine the functional consequences of
      these protein-protein interactions, point mutations were introduced into the gp59
      protein. Mutations were chosen based on the available crystal structure and
      focused on hydrophobic residues with a high degree of solvent accessibility.
      Characterization of the mutant proteins revealed a single mutation, Y122A, which
      is defective in polymerase binding and has weakened affinity for the helicase.
      The interaction between single-stranded DNA-binding protein and Y122A is
      unaffected, as is the affinity of Y122A for DNA substrates. When standard
      concentrations of helicase are employed, Y122A is unable to productively load the
      helicase onto forked DNA substrates. As a result of the loss of polymerase
      binding, Y122A cannot inhibit the polymerase during nucleotide idling or prevent
      it from removing the primer strand of a D-loop. However, Y122A is capable of
      inhibiting strand displacement synthesis by polymerase. The retention of strand
      displacement inhibition by Y122A, even in the absence of a gp59-polymerase
      interaction, indicates that there are two modes of polymerase inhibition by gp59.
      Inhibition of the polymerase activity only requires gp59 to bind to the
      replication fork, whereas inhibition of the exonuclease activity requires an
      interaction between the polymerase and gp59. The inability of Y122A to interact
      with both the polymerase and the helicase suggests a mechanism for polymerase
      unlocking by the helicase based on a direct competition between the helicase and
      polymerase for an overlapping binding site on gp59.

PMID- 16407254
TI  - Long chain base tolerance in Saccharomyces cerevisiae is induced by retrograde
      signals from the mitochondria.
AB  - Saccharomyces cerevisiae cells lacking their mitochondrial DNA (rho0 cells)
      respond to this loss of genetic information by induction of a program of nuclear
      gene expression called the retrograde response. Expression of genes involved in
      multidrug resistance and sphingolipid biosynthesis is coordinately induced in
      rho0 cells by the zinc cluster transcription factor Pdr3p. In this report, we
      identify a membrane protein involved in control of intracellular levels of a
      sphingolipid precursor as a transcriptional target of the Pdr3p-mediated
      retrograde response. These sphingolipid precursors are called long chain bases
      (LCBs) and increased LCB levels are growth inhibitory. This membrane protein has
      been designated Rsb1p and has previously been shown to act as a LCB transporter
      protein and to be a component of the endoplasmic reticulum. These earlier studies
      used an amino-terminal truncated form of Rsb1p. Here we employ a full-length form
      of Rsb1p and find that this protein is localized to the plasma membrane and is
      modified by N-linked glycosylation. Two glycosylation sites are present in the
      Rsb1p and both are required for normal LCB resistance. Mutational analysis of the
      RSB1 promoter revealed that two Pdr3p binding sites are present and both of these
      are required for normal retrograde induction of transcription. LCB tolerance is
      strongly increased in rho0 cells but this increase is ablated in rho0 rsb1Delta
      cells. Together, these data indicate Pdr3p activation of RSB1 transcription is an
      important feature of the retrograde response allowing normal detoxification of an
      endogenous sphingolipid precursor.

PMID- 16407255
TI  - Association of a model class A (apolipoprotein) amphipathic alpha helical peptide
      with lipid: high resolution NMR studies of peptide.lipid discoidal complexes.
AB  - Class A amphipathic helical peptides have been shown to mimic apolipoprotein A-I,
      the major protein component of high density lipoproteins and have been shown to
      inhibit atherosclerosis in several dyslipidemic mouse models. Previously we
      reported the NMR structure of Ac-18A-NH2, the base-line model class A amphipathic
      helical peptide in a 50% (v/v) trifluoroethanol-d3/water mixture, a membrane
      mimic environment (Mishra, V. K., Palgunachari, M. N., Anantharamaiah, G. M.,
      Jones, M. K., Segrest, J. P., and Krishna, N. R. (2001) Peptides 22, 567-573).
      The peptide Ac-18A-NH2 forms discoidal nascent high density lipoprotein-like
      particles with 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Because subtle
      structural changes in the peptide.lipid complexes have been shown to be
      responsible for their antiatherogenic properties, we undertook high resolution
      NMR studies to deduce detailed structure of recombinant peptide.1,2-dimyristoyl
      sn-glycero-3-phosphocholine complexes. The peptide adopts a well defined
      amphipathic alpha helical structure in association with the lipid at a 1:1
      peptide:lipid weight ratio. Nuclear Overhauser effect spectroscopy revealed a
      number of intermolecular close contacts between the aromatic residues in the
      hydrophobic face of the helix and the lipid acyl chain protons. The pattern of
      observed peptide-lipid nuclear Overhauser effects is consistent with a parallel
      orientation of the amphipathic alpha helix, with respect to the plane of the
      lipid bilayer, on the edge of the disc (the belt model). Based on the results of
      chemical cross-linking and molecular modeling, we propose that peptide helices
      are arranged in a head to tail fashion to cover the edge of the disc. This
      arrangement of peptides is also consistent with the pKa values of the Lys
      residues determined previously. Taken together, these results provide for the
      first time a high resolution structural view of the peptide.lipid discoidal
      complexes formed by a class A amphipathic alpha helical peptide.

PMID- 16407256
TI  - Different mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and
      CDK2/cyclin A dynamics.
AB  - A detailed analysis is presented of the dynamics of human CDK5 in complexes with
      the protein activator p25 and the purine-like inhibitor roscovitine. These and
      other findings related to the activation of CDK5 are critically reviewed from a
      molecular perspective. In addition, the results obtained on the behavior of CDK5
      are compared with data on CDK2 to assess the differences and similarities between
      the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit
      association, (iii) conformational changes in the T-loop following CDK/regulatory
      subunit complex formation, and (iv) specificity in CDK/regulatory subunit
      recognition. An energy decomposition analysis, used for these purposes, revealed
      why the binding of p25 alone is sufficient to stabilize the extended active T
      loop conformation of CDK5, whereas the equivalent conformational change in CDK2
      requires both the binding of cyclin A and phosphorylation of the Thr(160)
      residue. The interaction energy of the CDK5 T-loop with p25 is about 26 kcal.mol(
      1) greater than that of the CDK2 T-loop with cyclin A. The binding pattern
      between CDK5 and p25 was compared with that of CDK2/cyclin A to find specific
      regions involved in CDK/regulatory subunit recognition. The analyses performed
      revealed that the alphaNT-helix of cyclin A interacts with the alpha6-alpha7 loop
      and the alpha7 helix of CDK2, but these regions do not interact in the CDK5/p25
      complex. Further differences between the CDK5/p25 and CDK2/cyclin A systems
      studied are discussed with respect to their specific functionality.

PMID- 16407257
TI  - Enhanced alpha1 microglobulin secretion from Hepatitis E virus ORF3-expressing
      human hepatoma cells is mediated by the tumor susceptibility gene 101.
AB  - Viruses are known to exploit the host cell machinery for their benefit during
      different stages of their life cycle within the infected host. One of the major
      challenges for a virus during the early stages of infection is to escape
      recognition by the host immune system. Viruses have adopted many novel strategies
      to evade the host immune response or to create an immune suppressed environment.
      An earlier study in our laboratory has demonstrated that the ORF3 protein of the
      hepatitis E virus expedites the secretion of alpha1 microglobulin, an
      immunosuppressant molecule. Based on this observation, we proposed that enhanced
      secretion of alpha1 microglobulin may help maintain an immunosuppressed milieu
      around the infected hepatocyte (Tyagi, S., Surjit, M., Roy, A. K., Jameel, S.,
      and Lal, S. K. (2004) J. Biol. Chem. 279, 29308-29319). In the present study, we
      discovered that the ability of the ORF3 protein to expedite alpha1 microglobulin
      secretion is attributed to the PSAP motif present at the C terminus of the
      former. The ORF3 protein was able to associate with the tumor susceptibility gene
      101 (TSG101) through the PSAP motif. Further, a PSAP motif-mutated ORF3 protein
      was unable to associate with TSG101 and also lost its ability to enhance the
      secretion of alpha1 microglobulin. In addition, the ORF3 protein was found to
      associate simultaneously with TSG101 and alpha1 microglobulin because all three
      of them were co-precipitated as a ternary complex. Finally, a dominant negative
      mutant of the VPS4 protein was shown to block the enhanced alpha1 microglobulin
      secretion in ORF3-expressing hepatocytes. These results suggest a mechanism by
      which the ORF3 protein exploits the endosomal sorting machinery to enhance the
      secretion of an immunosuppressant molecule (alpha1 microglobulin) from the
      cultured hepatocytes.

PMID- 16407258
TI  - Antagonistic effects of oxidized low density lipoprotein and alpha-tocopherol on
      CD36 scavenger receptor expression in monocytes: involvement of protein kinase B
      and peroxisome proliferator-activated receptor-gamma.
AB  - Vitamin E deficiency increases expression of the CD36 scavenger receptor,
      suggesting specific molecular mechanisms and signaling pathways modulated by
      alpha-tocopherol. We show here that alpha-tocopherol down-regulated CD36
      expression (mRNA and protein) in oxidized low density lipoprotein (oxLDL)
      stimulated THP-1 monocytes, but not in unstimulated cells. Furthermore, alpha
      tocopherol treatment of monocytes led to reduction of fluorescent oxLDL-3,3'
      dioctadecyloxacarbocyanine perchlorate binding and uptake. Protein kinase C (PKC)
      appears not to be involved because neither activation of PKC by phorbol 12
      myristate 13-acetate nor inhibition by PKC412 was affected by alpha-tocopherol.
      However, alpha-tocopherol could partially prevent CD36 induction after
      stimulation with a specific agonist of peroxisome proliferator-activated receptor
      gamma (PPARgamma; troglitazone), indicating that this pathway is susceptible to
      alpha-tocopherol action. Phosphorylation of protein kinase B (PKB) at Ser473 was
      increased by oxLDL, and alpha-tocopherol could prevent this event. Expression of
      PKB stimulated the CD36 promoter as well as a PPARgamma element-driven reporter
      gene, whereas an inactive PKB mutant had no effect. Moreover, coexpression of
      PPARgamma and PKB led to additive induction of CD36 expression. Altogether, our
      results support the existence of PKB/PPARgamma signaling pathways that mediate
      CD36 expression in response to oxLDL. The activation of CD36 expression by PKB
      suggests that both lipid biosynthesis and fatty acid uptake are stimulated by
      PKB.

PMID- 16407259
TI  - Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by cdc2
      regulates endothelial cell proliferation.
AB  - RUNX2 is a member of the runt family of DNA-binding transcription factors. RUNX2
      mediates endothelial cell migration and invasion during tumor angiogenesis and is
      expressed in metastatic breast and prostate tumors. Our published studies showed
      that RUNX2 DNA-binding activity is low during growth arrest, but elevated in
      proliferating endothelial cells. To investigate its role in cell proliferation
      and cell cycle regulation, RUNX2 was depleted in human bone marrow endothelial
      cells using RNA interference. Specific RUNX2 depletion inhibited DNA-binding
      activity as measured by electrophoretic mobility shift assay resulting in
      inhibition of cell proliferation. Cells were synchronized at the G(1)/S boundary
      with excess thymidine or in mitosis (M phase) with nocodazole. Endogenous or
      ectopic RUNX2 activity was maximal at late G(2) and during M phase. Inhibition of
      RUNX2 expression by RNA interference delayed entry into and exit out of the
      G(2)/M phases of the cell cycle. RUNX2 was coimmunoprecipitated with cyclin B1 in
      mitotic cells, which further supported a role for RUNX2 in cell cycle
      progression. Moreover, in vitro kinase assays using recombinant cdc2 kinase
      showed that RUNX2 was phosphorylated at Ser(451). The cdc2 inhibitor roscovitine
      dose dependently inhibited in vivo RUNX2 DNA-binding activity during mitosis and
      the RUNX2 mutant S451A exhibited lower DNA-binding activity and reduced
      stimulation of anchorage-independent growth relative to wild type RUNX2. These
      results suggest for the first time that RUNX2 phosphorylation by cdc2 may
      facilitate cell cycle progression possibly through regulation of G(2) and M
      phases, thus promoting endothelial cell proliferation required for tumor
      angiogenesis.

PMID- 16407260
TI  - Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex.
AB  - In Saccharomyces cerevisiae, the Hop2 protein forms a complex with the Mnd1
      protein and is required for the alignment of homologous chromosomes during
      meiosis, probably through extensive homology matching between them. The Rad51 and
      Dmc1 proteins, the eukaryotic RecA orthologs, promote strand exchange and may
      function in the extensive matching of homology within paired DNA molecules. In
      the present study, we purified the human TBPIP/Hop2-Mnd1 complex and found that
      it significantly stimulates the Dmc1- and Rad51-mediated strand exchange. The
      human Hop2-Mnd1 complex preferentially binds to a three-stranded DNA branch,
      which mimics the strand-exchange intermediate. These findings are consistent with
      genetic data, which showed that the Hop2 and Mnd1 proteins are required for
      homology matching between homologous chromosomes. Therefore, the human TBPIP/Hop2
      Mnd1 complex may ensure proper pairing between homologous chromosomes through its
      stimulation of strand exchange during meiosis.

PMID- 16407261
TI  - Sumoylation inhibits cleavage of Sp1 N-terminal negative regulatory domain and
      inhibits Sp1-dependent transcription.
AB  - Sp1 is a ubiquitously expressed transcription factor that binds GC-rich cis
      elements. Many posttranslational modifications have been implicated in the
      regulation of Sp1 activity. We now provide evidence for a novel mechanism of Sp1
      regulation involving the small ubiquitin-like modifier (SUMO-1). Western blot
      analysis revealed a high molecular mass Sp1 of 125 kDa that is stabilized by a
      selective SUMO hydrolase inhibitor and destabilized by a specific SUMO-1
      hydrolase. The covalent modification of Sp1 by endogenous SUMO-1 and SUMO-1 that
      has been fused to green fluorescent protein was demonstrated using transient
      transfection assays. A high probability sumoylation consensus motif,
      VK(16)IE(18), is located within the N-terminal negative regulatory domain of Sp1.
      Either arginine substitution for lysine 16 (Sp1(K16R)) or alanine substitution
      for glutamic acid 18 (Sp1(E18A)), abrogated Sp1 sumoylation. In vitro SUMO-1
      covalently bound affinity-purified GST-Sp1, but not GST-Sp1(K16R). In vivo Sp1
      was determined to be N-terminally cleaved, while Sp1(K16R) could not be cleaved
      indicating that sumoylation and cleavage are coupled through the key regulatory
      lysine 16. This coupling was evident by the demonstration of an inverse
      relationship between cellular SUMO-modified Sp1 and N-terminally cleaved Sp1.
      Compared with Sp1, sumoylation-deficient Sp1(E18A) exhibited enhanced cleavage
      and was a better transcriptional activator, while constitutively SUMO-1-modified
      Sp1 was deficient in proteolytic processing and repressed Sp1 transcriptional
      activity. The repressive effect of sumoylation on Sp1 activity is emphasized
      through the use of a GAL4 based transactivation assay. A model is proposed
      defining a mechanism by which sumoylation preserves the integrity of a negative
      regulatory domain thereby allowing for the inhibition of Sp-dependent
      transcription.

PMID- 16407262
TI  - Plant sulfite oxidase as novel producer of H2O2: combination of enzyme catalysis
      with a subsequent non-enzymatic reaction step.
AB  - Sulfite oxidase (EC 1.8.3.1) from the plant Arabidopsis thaliana is the smallest
      eukaryotic molybdenum enzyme consisting of a molybdenum cofactor-binding domain
      but lacking the heme domain that is known from vertebrate sulfite oxidase. While
      vertebrate sulfite oxidase is a mitochondrial enzyme with cytochrome c as the
      physiological electron acceptor, plant sulfite oxidase is localized in
      peroxisomes and does not react with cytochrome c. Here we describe results that
      identified oxygen as the terminal electron acceptor for plant sulfite oxidase and
      hydrogen peroxide as the product of this reaction in addition to sulfate. The
      latter finding might explain the peroxisomal localization of plant sulfite
      oxidase. 18O labeling experiments and the use of catalase provided evidence that
      plant sulfite oxidase combines its catalytic reaction with a subsequent non
      enzymatic step where its reaction product hydrogen peroxide oxidizes another
      molecule of sulfite. In vitro, for each catalytic cycle plant SO will bring about
      the oxidation of two molecules of sulfite by one molecule of oxygen. In the
      plant, sulfite oxidase could be responsible for removing sulfite as a toxic
      metabolite, which might represent a means to protect the cell against excess of
      sulfite derived from SO2 gas in the atmosphere (acid rain) or during the
      decomposition of sulfur-containing amino acids. Finally we present a model for
      the metabolic interaction between sulfite and catalase in the peroxisome.

PMID- 16407263
TI  - CCAAT enhancer-binding protein alpha suppresses the rat placental glutathione S
      transferase gene in normal liver.
AB  - The rat placental glutathione S-transferase (GST-P), an isozyme of glutathione S
      transferase, is not expressed in normal liver but is highly induced at an early
      stage of chemical hepatocarcinogenesis and in hepatomas. Recently, we reported
      that the NF-E2 p45-related factor 2 (Nrf2)/MafK heterodimer binds to GST-P
      enhancer 1 (GPE1), a strong enhancer of the GST-P gene, and activates this gene
      in preneoplastic lesions and hepatomas. In addition to the positive regulation
      during hepatocarcinogenesis, negative regulatory mechanisms might work to repress
      GST-P in normal liver, but this remains to be clarified. In this work, we
      identify the CCAAT enhancer-binding protein alpha (C/EBPalpha) as a negative
      regulator that binds to GPE1 and suppresses GST-P expression in normal liver.
      C/EBPalpha binds to part of the GPE1 sequence, and the binding of Nrf2/MafK and
      C/EBPalpha to GPE1 is mutually exclusive. In a transient-transfection analysis,
      C/EBPalpha activated GPE1 in F9 embryonal carcinoma cells but strongly inhibited
      GPE1 activity in hepatoma cells. The expression of C/EBPalpha was specifically
      suppressed in GST-P-positive preneoplastic foci in the livers of
      carcinogentreated rats. A chromatin immunoprecipitation analysis showed that
      C/EBPalpha bound to GPE1 in the normal liver in vivo but did not bind in
      preneoplastic hepatocytes. Introduction of the C/EBPalpha gene fused with the
      estrogen receptor ligand-binding domain into hepatoma cells, and subsequent
      activation by beta-estradiol led to the suppression of endogenous GST-P
      expression. These results indicate that C/EBPalpha is a negative regulator of GST
      P gene expression in normal liver.

PMID- 16407265
TI  - Molecular mechanism of alpha 1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome:
      unfolding of an N-anchor domain at the N-terminal end of the type I collagen
      triple helix.
AB  - We demonstrate that 85 N-terminal amino acids of the alpha1(I) chain participate
      in a highly stable folding domain, acting as the stabilizing anchor for the amino
      end of the type I collagen triple helix. This anchor region is bordered by a
      microunfolding region, 15 amino acids in each chain, which include no proline or
      hydroxyproline residues and contain a chymotrypsin cleavage site. Glycine
      substitutions and amino acid deletions within the N-anchor domain induce its
      reversible unfolding above 34 degrees C. The overall triple helix denaturation
      temperature is reduced by 5-6 degrees C, similar to complete N-anchor removal. N
      propeptide partially restores the stability of mutant procollagen but not
      sufficiently to prevent N-anchor unfolding and a conformational change at the N
      propeptide cleavage site. The ensuing failure of N-proteinase to cleave at the
      misfolded site leads to incorporation of pN-collagen into fibrils. Similar, but
      weaker, effects are caused by G88E substitution in the adjacent triplet, which
      appears to alter N-anchor structure as well. As in Ehlers-Danlos syndrome (EDS)
      VIIA/B, fibrils containing pN-collagen are thinner and weaker causing EDS-like
      laxity of large and small joints and paraspinal ligaments. However, distinct
      structural consequences of N-anchor destabilization result in a distinct
      alpha1(I)-osteogenesis imperfecta (OI)/EDS phenotype.

PMID- 16407264
TI  - SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory
      signaling by mediating ASK1 degradation.
AB  - We have previously shown that ASK1 undergoes ubiquitination and degradation in
      resting endothelial cells (EC) and that proinflammatory cytokine tumor necrosis
      factor (TNF) induces deubiquitination and stabilization, leading to ASK1
      activation. However, the mechanism for the regulation of ASK1 stability is not
      known. In the present study, we have shown that SOCS1, a member of suppressor of
      cytokine signaling, induces ASK1 degradation. SOCS1 was constitutively expressed
      in EC and formed a labile complex with ASK1 that can be stabilized by proteasomal
      inhibitors. The phosphotyrosine-binding SH2 domain of SOCS1 was critical for its
      association with ASK1. Thus a SOCS1 mutant defective in phosphotyrosine binding
      failed to bind to and induce ASK1 degradation. Phosphotyrosine of ASK1 was
      induced in response to growth factors, and TNF induced dephosphorylation and
      dissociation of ASK1 from SOCS1. ASK1 with a mutation at Tyr-718 diminished the
      binding to SOCS1, suggesting that the phosphotyrosine-718 of ASK1 is critical for
      SOCS1 binding. Moreover, ASK1 expression and activity were up-regulated in SOCS1
      deficient mice and derived EC, resulting in enhanced TNF-induced activation of
      JNK, expression of proinflammatory molecules, and apoptotic responses. We
      concluded that SOCS1 functions as a negative regulator in TNF-induced
      inflammation in EC, in part, by inducing ASK1 degradation.

PMID- 16407266
TI  - Carbon catabolite repression regulates amino acid permeases in Saccharomyces
      cerevisiae via the TOR signaling pathway.
AB  - We have identified carbon catabolite repression (CCR) as a regulator of amino
      acid permeases in Saccharomyces cerevisiae, elucidated the permeases regulated by
      CCR, and identified the mechanisms involved in amino acid permease regulation by
      CCR. Transport of l-arginine and l-leucine was increased by approximately 10-25
      fold in yeast grown in carbon sources alternate to glucose, indicating regulation
      by CCR. In wild type yeast the uptake (pmol/10(6) cells/h), in glucose versus
      galactose medium, of l-[(14)C]arginine was (0.24 +/- 0.04 versus 6.11 +/- 0.42)
      and l-[(14)C]leucine was (0.30 +/- 0.02 versus 3.60 +/- 0.50). The increase in
      amino acid uptake was maintained when galactose was replaced with glycerol.
      Deletion of gap1Delta and agp1Delta from the wild type strain did not alter CCR
      induced increase in l-leucine uptake; however, deletion of further amino acid
      permeases reduced the increase in l-leucine uptake in the following manner: 36%
      (gnp1Delta), 62% (bap2Delta), 83% (Delta(bap2-tat1)). Direct immunofluorescence
      showed large increases in the expression of Gnp1 and Bap2 proteins when grown in
      galactose compared with glucose medium. By extending the functional genomic
      approach to include major nutritional transducers of CCR in yeast, we concluded
      that SNF/MIG, GCN, or PSK pathways were not involved in the regulation of amino
      acid permeases by CCR. Strikingly, the deletion of TOR1, which regulates cellular
      response to changes in nitrogen availability, from the wild type strain abolished
      the CCR-induced amino acid uptake. Our results provide novel insights into the
      regulation of yeast amino acid permeases and signaling mechanisms involved in
      this regulation.

PMID- 16407267
TI  - The histone chaperone Asf1 increases the rate of histone eviction at the yeast
      PHO5 and PHO8 promoters.
AB  - Eukaryotic gene expression starts off from a largely obstructive chromatin
      substrate that has to be rendered accessible by regulated mechanisms of chromatin
      remodeling. The yeast PHO5 promoter is a well known example for the contribution
      of positioned nucleosomes to gene repression and for extensive chromatin
      remodeling in the course of gene induction. Recently, the mechanism of this
      remodeling process was shown to lead to the disassembly of promoter nucleosomes
      and the eviction of the constituent histones in trans. This finding called for a
      histone acceptor in trans and thus made histone chaperones likely to be involved
      in this process. In this study we have shown that the histone chaperone Asf1
      increases the rate of histone eviction at the PHO5 promoter. In the absence of
      Asf1 histone eviction is delayed, but the final outcome of the chromatin
      transition is not affected. The same is true for the coregulated PHO8 promoter
      where induction also leads to histone eviction and where the rate of histone loss
      is reduced in asf1 strains as well, although less severely. Importantly, the
      final extent of chromatin remodeling is not affected. We have also presented
      evidence that Asf1 and the SWI/SNF chromatin remodeling complex work in distinct
      parallel but functionally overlapping pathways, i.e. they both contribute toward
      the same outcome without being mutually strictly dependent.

PMID- 16407268
TI  - Interactions involved in the realignment of membrane-associated helices. An
      investigation using oriented solid-state NMR and attenuated total reflection
      Fourier transform infrared spectroscopies.
AB  - A series of histidine-containing peptides (LAH4X6) was designed to investigate
      the membrane interactions of selected side chains. To this purpose, their pH
      dependent transitions from in-plane to transmembrane orientations were
      investigated by attenuated total reflection Fourier transform infrared and
      oriented solid-state NMR spectroscopies. Peptides of the same family have
      previously been shown to exhibit antibiotic and DNA transfection activities.
      Solution NMR spectroscopy indicates that these peptides form amphipathic helical
      structures in membrane environments, and the technique was also used to
      characterize the pK values of all histidines in the presence of detergent
      micelles. Whereas one face of the amphipathic helix is clearly hydrophobic, the
      opposite side is flanked by four histidines surrounding six leucine, alanine,
      glycine, tryptophan, or tyrosine residues, respectively. This diversity in
      peptide composition causes pronounced shifts in the midpoint pH of the in-plane
      to transmembrane helical transition, which is completely abolished for the
      peptides carrying the most hydrophilic amino acid residues. These properties open
      up a conceptually new approach to study in a quantitative manner the hydrophobic
      as well as specific interactions of amino acids in membranes. Notably, the
      resulting scale for whole residue transitions from the bilayer interface to the
      hydrophobic membrane interior is obtained from extended helical sequences in
      lipid bilayers.

PMID- 16407269
TI  - BopC is a novel type III effector secreted by Bordetella bronchiseptica and has a
      critical role in type III-dependent necrotic cell death.
AB  - In Bordetella bronchiseptica, the functional type III secretion system (TTSS) is
      required for the induction of necrotic cell death in infected mammalian cells. To
      identify the factor(s) involved in necrotic cell death, type III-secreted
      proteins from B. bronchiseptica were analyzed using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and electrospray
      ionization tandem mass spectrometry. We identified a 69-kDa secreted protein
      designated BopC. The gene encoding BopC is located outside of the TTSS locus and
      is also highly conserved in both Bordetella parapertussis and Bordetella
      pertussis. The results of a lactate dehydrogenase release assay and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay
      demonstrated that BopC is required for necrotic cell death. It has been reported
      that tyrosine-phosphorylated proteins (PY) of host cells are dephosphorylated
      during B. bronchiseptica infection in a TTSS-dependent manner. We found that BopC
      is also involved in PY dephosphorylation in infected host cells. It appears that
      the necrotic cell death triggered by BopC occurs prior to the PY reduction in
      host cells, because Bordetella-induced cell death was not affected even in the
      presence of a dephosphorylation inhibitor. Furthermore, a translocation assay
      showed that the signal sequence for both secretion into culture supernatant and
      translocation into the host cell is located in 48 amino acid residues of the BopC
      N terminus. This report reveals for the first time that a novel type III
      effector, BopC, is required for the induction of necrotic cell death during
      Bordetella infection.

PMID- 16407270
TI  - Carbonic anhydrase subunits form a matrix-exposed domain attached to the membrane
      arm of mitochondrial complex I in plants.
AB  - Complex I of Arabidopsis includes five structurally related subunits representing
      gamma-type carbonic anhydrases termed CA1, CA2, CA3, CAL1, and CAL2. The position
      of these subunits within complex I was investigated. Direct analysis of isolated
      subcomplexes of complex I by liquid chromatography linked to tandem mass
      spectrometry allowed the assignment of the CA subunits to the membrane arm of
      complex I. Carbonate extraction experiments revealed that CA2 is an integral
      membrane protein that is protected upon protease treatment of isolated
      mitoplasts, indicating a location on the matrix-exposed side of the complex. A
      structural characterization by single particle electron microscopy of complex I
      from the green alga Polytomella and a previous analysis from Arabidopsis indicate
      a plant-specific spherical extra-domain of about 60 A in diameter, which is
      attached to the central part of the membrane arm of complex I on its matrix face.
      This spherical domain is proposed to contain a heterotrimer of three CA subunits,
      which are anchored with their C termini to the hydrophobic arm of complex I.
      Functional implications of the complex I-integrated CA subunits are discussed.

PMID- 16407272
TI  - Involvement of endonuclease G in nucleosomal DNA fragmentation under sustained
      endogenous oxidative stress.
AB  - We have previously shown that inhibition of catalase and glutathione peroxidase
      activities by 3-amino-1,2,4-triazole (ATZ) and mercaptosuccinic acid (MS),
      respectively, in rat primary hepatocytes caused sustained endogenous oxidative
      stress and apoptotic cell death without caspase-3 activation. In this study, we
      investigated the mechanism of this apoptotic cell death in terms of nucleosomal
      DNA fragmentation. Treatment with ATZ+MS time-dependently increased the number of
      deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL)-positive nuclei
      from 12 h, resulting in clear DNA laddering at 24 h. The deoxyribonuclease
      (DNase) inhibitor, aurintricarboxylic acid (ATA), completely inhibited
      nucleosomal DNA fragmentation but the pan-caspase inhibitor, z-VAD-fmk was
      without effects; furthermore, the cleavage of inhibitor of caspase-activated
      DNase was not detected, indicating the involvement of DNase(s) other than caspase
      activated DNase. Considering that endonuclease G (EndoG) reportedly acts in a
      caspase-independent manner, we cloned rat EndoG cDNA for the first time.
      Recombinant EndoG alone digested plasmid DNA and induced nucleosomal DNA
      fragmentation in isolated hepatocyte nuclei. Recombinant EndoG activity was
      inhibited by ATA but not by hydrogen peroxide, even at 10 mm. ATZ+MS stimulation
      elicited decreases in mitochondrial membrane potential and EndoG translocation
      from mitochondria to nuclei. By applying RNA interference, the mRNA levels of
      EndoG were almost completely suppressed and the amount of EndoG protein was
      decreased to approximately half the level of untreated cells. Under these
      conditions, decreases in TUNEL-positive nuclei were significantly suppressed.
      These results indicate that EndoG is responsible, at least in part, for
      nucleosomal DNA fragmentation under endogenous oxidative stress conditions
      induced by ATZ+MS.

PMID- 16407271
TI  - Antiapoptotic effects of erythropoietin in differentiated neuroblastoma SH-SY5Y
      cells require activation of both the STAT5 and AKT signaling pathways.
AB  - The hematopoietic cytokine erythropoietin (Epo) prevents neuronal death during
      ischemic events in the brain and in neurodegenerative diseases, presumably
      through its antiapoptotic effects. To explore the role of different signaling
      pathways in Epo-mediated antiapoptotic effects in differentiated human
      neuroblastoma SH-SY5Y cells, we employed a prolactin receptor
      (PrlR)/erythropoietin receptor (EpoR) chimera system, in which binding of
      prolactin (Prl) to the extracellular domain activates EpoR signaling in the
      cytosol. On induction of apoptosis by staurosporine, Prl supports survival of the
      SH-SY5Y cells expressing the wild-type PrlR/EpoR chimera. In these cells Prl
      treatment strongly activates the STAT5, AKT, and MAPK signaling pathways and
      induces weak activation of the p65 NF-kappaB factor. Selective mutation of the
      eight tyrosine residues of the EpoR cytoplasmic domain results in impaired or
      absent activation of either STAT5 (mutation of Tyr(343)) or AKT (mutation of
      Tyr(479)) or both (mutation of all eight tyrosine residues). Most interestingly,
      Prl treatment does not prevent apoptosis in cells expressing mutant PrlR/EpoR
      chimeras in which either the STAT5 or the AKT signaling pathways are not
      activated. In contrast, ERK 1/2 is fully activated by all mutant PrlR/EpoR
      chimeras, comparable with the level seen with the wild-type PrlR/EpoR chimera,
      implying that activation of the MAPK signaling pathway per se is not sufficient
      for antiapoptotic activity. Therefore, the antiapoptotic effects of Epo in
      neuronal cells require the combinatorial activation of multiple signaling
      pathways, including STAT5, AKT, and potentially MAPK as well, in a manner similar
      to that observed in hematopoietic cells.

PMID- 16407273
TI  - Phosphorylation of histones by tissue transglutaminase.
AB  - Tissue transglutaminase 2 (TG2) has recently been shown to have intrinsic
      serine/threonine kinase activity. Since histones are known to be cross-linked by
      TG2, we investigated whether histones are also substrates for TG2 kinase
      activity. TG2 was able to phosphorylate H1, H2A, H2B, H3, and H4 histones in
      vitro. Using peptide substrates and phosphospecific antibodies we demonstrated
      that TG2 phosphorylated Ser(10) in H3 and that this phosphorylation was reduced
      by acetylation, whereas phosphorylation of Ser(10) by TG2 enhanced acetylation.
      Furthermore we demonstrated that exogenous TG2 phosphorylated H1 and H3 in
      nucleosome preparations. We examined the abundance of TG2 in DNA-associated
      proteins from MCF-7 cells treated with phorbol ester (TPA) and 17beta-estradiol
      (E2). TG2 abundance was significantly reduced in E2-treated cells and enhanced in
      TPA-treated cells. In summary we have demonstrated that TG2 is able to
      phosphorylate purified histone proteins, and H3 and H1 in chromatin preparations,
      and it is associated with chromatin in breast cancer cells. These studies suggest
      a novel role for TG2 in the regulation of chromatin structure and function.

PMID- 16407274
TI  - Effector-repressor interactions, binding of a single effector molecule to the
      operator-bound TtgR homodimer mediates derepression.
AB  - The RND family transporter TtgABC and its cognate repressor TtgR from Pseudomonas
      putida DOT-T1E were both shown to possess multidrug recognition properties.
      Structurally unrelated molecules such as chloramphenicol, butyl paraben, 1,3
      dihydroxynaphthalene, and several flavonoids are substrates of TtgABC and
      activate pump expression by binding to the TtgR-operator complex. Isothermal
      titration calorimetry was employed to determine the thermodynamic parameters for
      the binding of these molecules to TtgR. Dissociation constants were in the range
      from 1 to 150 microm, the binding stoichiometry was one effector molecule per
      dimer of TtgR, and the process was driven by favorable enthalpy changes. Although
      TtgR exhibits a large multidrug binding profile, the plant-derived compounds
      phloretin and quercetin were shown to bind with the highest affinity (K(D) of
      around 1 microm), in contrast to other effectors (chloramphenicol and aromatic
      solvents) for which exhibited a more reduced affinity. Structure-function studies
      of effectors indicate that the presence of aromatic rings as well as hydroxyl
      groups are determinants for TtgR binding. The binding of TtgR to its operator DNA
      does not alter the protein effector profile nor the effector binding
      stoichiometry. Moreover, we demonstrate here for the first time that the binding
      of a single effector molecule to the DNA-bound TtgR homodimer induces the
      dissociation of the repressor-operator complex. This provides important insight
      into the molecular mechanism of effector-mediated derepression.

PMID- 16407275
TI  - Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil
      affinity: its orientation impacts cGMP but not cAMP affinity.
AB  - The side group of an invariant Gln in cGMP- and cAMP-specific phosphodiesterases
      (PDE) is held in different orientations by bonds with other amino acids and
      purportedly discriminates between guanine and adenine in cGMP and cAMP. In cGMP
      specific PDE5, Gln(775) constrains the orientation of the invariant Gln(817) side
      chain, which forms bidentate bonds with 5'-GMP, vardenafil, sildenafil, and 3
      isobutyl-1-methylxanthine (IBMX) (Sung, B. J., Hwang, K. Y., Jeon, Y. H., Lee, J.
      I., Heo, Y. S., Kim, J. H., Moon, J., Yoon, J. M., Hyun, Y. L., Kim, E., Eum, S.
      J., Park, S. Y., Lee, J. O., Lee, T. G., Ro, S., and Cho, J. M. (2003) Nature
      425, 98-102; Huai, Q., Liu, Y., Francis, S. H., Corbin, J. D., and Ke, H. (2004)
      J. Biol. Chem. 279, 13095-13101; Zhang, K. Y., Card, G. L., Suzuki, Y., Artis, D.
      R., Fong, D., Gillette, S., Hsieh, D., Neiman, J., West, B. L., Zhang, C.,
      Milburn, M. V., Kim, S. H., Schlessinger, J., and Bollag, G. (2004) Mol. Cell 15,
      279-286). PDE5(Q817A) and PDE5(Q775A) were generated to test the hypotheses that
      Gln(817) is critical for cyclic nucleotide or inhibitor affinity and that
      Gln(775) immobilizes the Gln(817) side chain to provide cGMP/cAMP selectivity.
      Allosteric cGMP binding and the molecular mass of the mutant proteins were
      unchanged compared with PDE5(WT). For PDE5(Q817A), K(m) for cGMP or cAMP was
      weakened 60- or 2-fold, respectively. For PDE5(Q775A), K(m) for cGMP was weakened
      approximately 20-fold but was unchanged for cAMP. For PDE5(Q817A), vardenafil,
      sildenafil, and IBMX inhibitory potencies were weakened 610-, 48-, and 60-fold,
      respectively, indicating that Gln(817) is a major determinant of potency,
      especially for vardenafil, and that binding of vardenafil and sildenafil differs
      substantially. Sildenafil and vardenafil affinity were not significantly affected
      in PDE5(Q775A). It is concluded that Gln(817) is a positive determinant for PDE5
      affinity for cGMP and several inhibitors; Gln(775), which perhaps restricts
      rotation of Gln(817) side chain, is critical for cGMP affinity but has no
      measurable effect on affinity for cAMP, sildenafil, or vardenafil.

PMID- 16407276
TI  - The Rab5 guanine nucleotide exchange factor Rabex-5 binds ubiquitin (Ub) and
      functions as a Ub ligase through an atypical Ub-interacting motif and a zinc
      finger domain.
AB  - Rabex-5, the mammalian orthologue of yeast Vps9p, is a guanine nucleotide
      exchange factor for Rab5. Rabex-5 forms a tight complex with Rabaptin-5, a
      multivalent adaptor protein that also binds to Rab4, Rab5, and to domains present
      in gamma-adaptins and the Golgi-localized, gamma-ear-containing, ARF-binding
      proteins (GGAs). Rabaptin-5 augments the Rabex-5 exchange activity, thus
      generating GTP-bound, membrane-associated Rab5 that, in turn, binds Rabaptin-5
      and stabilizes the Rabex-5.Rabaptin-5 complex on endosomes. Although the Rabex
      5.Rabaptin-5 complex is critical to the regulation of endosomal fusion, the
      structural determinants of this interaction are unknown. Likewise, the possible
      binding and covalent attachment of ubiquitin to Rabex-5, two modifications that
      are critical to the function of yeast Vps9p in endosomal transport, have not been
      studied. In this study, we identify the 401-462 and 551-661 coiled-coils as the
      regions in Rabex-5 and Rabaptin-5, respectively, that interact with one another.
      We also demonstrate that Rabex-5 undergoes ubiquitination and binds ubiquitin,
      though not via its proposed C-terminal CUE-like domain. Instead, the N-terminal
      region of Rabex-5 (residues 1-76), comprising an A20-like Cys2/Cys2 zinc finger
      and an adjacent alpha-helix, is important for ubiquitin binding and
      ubiquitination. Importantly, we demonstrate that the Rabex-5 zinc finger displays
      ubiquitin ligase (E3) activity. These observations extend our understanding of
      the regulation of Rabex-5 by Rabaptin-5. Moreover, the demonstration that Rabex-5
      is a ubiquitin ligase that binds ubiquitin and undergoes ubiquitination indicates
      that its role in endosome fusion may be subject to additional regulation by
      ubiquitin-dependent modifications.

PMID- 16407277
TI  - Membrane topology of the transporter associated with antigen processing (TAP1)
      within an assembled functional peptide-loading complex.
AB  - The transporter associated with antigen processing (TAP) translocates antigenic
      peptides from the cytosol into the endoplasmic reticular lumen for subsequent
      loading onto major histocompatibility complex (MHC) class I molecules. These
      peptide-MHC complexes are inspected at the cell surface by cytotoxic T
      lymphocytes. Assembly of the functional peptide transport and loading complex
      depends on intra- and intermolecular packing of transmembrane helices (TMs).
      Here, we have examined the membrane topology of human TAP1 within an assembled
      and functional transport complex by cysteine-scanning mutagenesis. The
      accessibility of single cysteine residues facing the cytosol or endoplasmic
      reticular lumen was probed by a minimally invasive approach using membrane
      impermeable, thiol-specific fluorophores in semipermeabilized "living" cells.
      TAP1 contains ten transmembrane segments, which place the N and C termini in the
      cytosol. The transmembrane domain consists of a translocation core of six TMs, a
      building block conserved among most ATP-binding cassette transporters, and a
      unique additional N-terminal domain of four TMs, essential for tapasin binding
      and assembly of the peptide-loading complex. This study provides a first map of
      the structural organization of the TAP machinery within the macromolecular MHCI
      peptide-loading complex.

PMID- 16407278
TI  - Identification of a ubiquinone-binding site that affects autophosphorylation of
      the sensor kinase RegB.
AB  - Rhodobacter capsulatus regulates many metabolic processes in response to the
      level of environmental oxygen and the energy state of the cell. One of the key
      global redox regulators of the cell's metabolic physiology is the sensor kinase
      RegB that controls the synthesis of numerous energy generation and utilization
      processes. In this study, we have succeeded in purifying full-length RegB
      containing six transmembrane-spanning elements. Exogenous addition of excess
      oxidized coenzyme Q1 is capable of inhibiting RegB autophosphorylation
      approximately 6-fold. However, the addition of reduced coenzyme Q1 exhibits no
      inhibitory effect on kinase activity. A ubiquinone-binding site, as defined by
      azidoquinone photo affinity cross-linking, was determined to lie within a
      periplasmic loop between transmembrane helices 3 and 4 that contains a fully
      conserved heptapeptide sequence of GGXXNPF. Mutation of the phenylalanine in this
      heptapeptide renders RegB constitutively active in vivo, indicating that this
      domain is responsible for sensing the redox state of the ubiquinone pool and
      subsequently controlling RegB autophosphorylation.

PMID- 16407279
TI  - The N terminus of GTP gamma S-activated transducin alpha-subunit interacts with
      the C terminus of the cGMP phosphodiesterase gamma-subunit.
AB  - Dynamic regulation of G-protein signaling in the phototransduction cascade
      ensures the high temporal resolution of vision. In a key step, the activated
      alpha-subunit of transducin (Galphat-GTP) activates the cGMP phosphodiesterase
      (PDE) by binding the inhibitory gamma-subunit (PDEgamma). Significant progress in
      understanding the interaction between Galphat and PDEgamma was achieved by
      solving the crystal structure of the PDEgamma C-terminal peptide bound to Galphat
      in the transition state for GTP hydrolysis (Slep, K. C., Kercher, M. A., He, W.,
      Cowan, C. W., Wensel, T. G., and Sigler, P. B. (2001) Nature 409, 1071-1077).
      However, some of the structural elements of each molecule were absent in the
      crystal structure. We have probed the binding surface between the PDEgamma C
      terminus and activated Galphat bound to guanosine 5'-O-(3-thio)-triphosphate
      (GTPgammaS) using a series of full-length PDEgamma photoprobes generated by
      intein-mediated expressed protein ligation. For each of seven PDEgamma photoprobe
      species, expressed protein ligation allowed one benzoyl-L-phenylalaine
      substitution at selected hydrophobic C-terminal positions, and the addition of a
      biotin affinity tag at the extreme C terminus. We have detected photocross
      linking from several PDEgamma C-terminal positions to the Galphat-GTPgammaS N
      terminus, particularly from PDEgamma residue 73. The overall percentage of cross
      linking to the Galphat-GTPgammaSN terminus was analyzed using a far Western
      method for examining Galphat-GTPgammaS proteolytic digestion patterns.
      Furthermore, mass spectrometric analysis of cross-links to Galphat from a benzoyl
      phenylalanine replacement at PDEgamma position 86 localized the region of
      photoinsertion to Galphat N-terminal residues Galphat-(22-26). This novel
      Galphat/PDEgamma interaction suggests that the transducin N terminus plays an
      active role in signal transduction.

PMID- 16407280
TI  - Extracellular TNFR1 release requires the calcium-dependent formation of a
      nucleobindin 2-ARTS-1 complex.
AB  - Extracellular tumor necrosis factor (TNF) receptors function as TNF-binding
      proteins that modulate TNF activity. In human vascular endothelial cells (HUVEC),
      extracellular TNFR1 (type I TNF receptor, TNFRSF1A) is generated by two
      mechanisms, proteolytic cleavage of soluble TNFR1 ectodomains and the release of
      full-length 55-kDa TNFR1 in the membranes of exosome-like vesicles. TNFR1 release
      from HUVEC is known to involve the association between ARTS-1 (aminopeptidase
      regulator of TNFR1 shedding), an integral membrane aminopeptidase, and TNFR1. The
      goal of this study was to identify ARTS-1 binding partners that modulate TNFR1
      release to the extracellular space. A yeast two-hybrid screen of a human placenta
      cDNA library showed that NUCB2 (nucleobindin 2), via its helix-loop-helix
      domains, binds the ARTS-1 extracellular domain. The association between
      endogenous ARTS-1 and NUCB2 in HUVEC was demonstrated by co-immunoprecipitation
      experiments, which showed the formation of a calcium-dependent NUCB2.ARTS-1
      complex that associated with a subset of total cellular TNFR1. Confocal
      microscopy experiments demonstrated that this association involved a distinct
      population of NUCB2-containing intracytoplasmic vesicles. RNA interference was
      utilized to specifically knock down NUCB2 and ARTS-1 expression, which
      demonstrated that both are required for the constitutive release of a full-length
      55-kDa TNFR1 within exosome-like vesicles as well as the inducible proteolytic
      cleavage of soluble TNFR1 ectodomains. We propose that calcium-dependent
      NUCB2.ARTS-1 complexes, which associate with TNFR1 prior to its commitment to
      pathways that result in either the constitutive release of TNFR1 exosome-like
      vesicles or the inducible proteolytic cleavage of TNFR1 ectodomains, play an
      important role in mediating TNFR1 release to the extracellular compartment.

PMID- 16407281
TI  - Hemoglobin is expressed by alveolar epithelial cells.
AB  - Hemoglobin gene expression in non-erythroid cells has been previously reported in
      activated macrophages from adult mice and lens cells, and recent studies indicate
      that alveolar epithelial cells can be derived from hematopoietic stem cells. Our
      laboratory has now produced strong evidence that hemoglobin is expressed by
      alveolar type II (ATII) cells and Clara cells, the primary producers of pulmonary
      surfactant. ATII cells are also closely involved in innate immunity within the
      lung and are stem cells that differentiate into alveolar type I cells. Reverse
      transcriptase-PCR was used to measure the expression of transcripts from the
      alpha- and beta-globin gene clusters in several human and rodent pulmonary
      epithelial cells. Surprisingly, the two major globin mRNAs characteristic of
      adult erythroid precursor cells were clearly expressed in human A549 and H441
      cell lines, mouse MLE-15 cells, and primary ATII cells isolated from normal rat
      and mouse lungs. DNA sequencing verified that these PCR products were indeed the
      result of specific amplification of globin gene cDNAs. These alveolar epithelial
      cells also expressed the corresponding hemoglobin protein subunits as determined
      by Western blotting, and tandem mass spectrometry sequencing was used to verify
      the presence of both alpha- and beta-globin polypeptides in rat primary ATII
      cells. The function of hemoglobin expression by cells of the pulmonary epithelium
      will be determined by future studies, but this novel finding could potentially
      have important implications for the physiology and pathology of the lung.

PMID- 16407282
TI  - Down-regulation of histone deacetylases stimulates adipocyte differentiation.
AB  - Specific cell type differentiation is driven by programmed regulation of gene
      expression, which is the result of coordinated modulation of the transcription
      machinery and chromatin-remodeling factors. We present evidence here that the
      down-regulation of histone deacetylases is an important process during adipocyte
      differentiation. In 3T3-L1 cells, histone hyperacetylation was selectively
      induced at the promoter regions of adipogenic genes during adipocyte
      differentiation. Interestingly, this was accompanied by a dramatic decrease in
      the expression level of several histone deacetylases including HDAC1, -2, and -5
      and a reduction in overall histone deacetylase enzyme activity. Inhibition of
      histone deacetylase activity using sodium butyrate resulted in stimulation of
      adipogenic gene expression and adipocyte differentiation. Consistently, HDAC1
      knock-down promoted adipogenesis whereas HDAC1 overexpression attenuated
      adipocyte differentiation in 3T3-L1 cells. Together, these results suggest that
      the regulation of not only adipogenic transcription factors, but also chromatin
      modifying enzymes is crucial for the execution of bona fide adipogenesis.

PMID- 16407283
TI  - NF-kappaB regulates phagocytic NADPH oxidase by inducing the expression of
      gp91phox.
AB  - The superoxide-generating phagocytic NADPH oxidase is an important component of
      the innate immune response against microbial agents, and is involved in shaping
      the cellular response to a variety of physiological and pathological signals. One
      of the downstream targets of NADPH oxidase-derived radicals is the ubiquitous
      transcription factor NF-kappaB, which controls the expression of a large array of
      genes involved in immune function and cell survival. Here we show that NF-kappaB
      itself is a key factor in controlling NADPH oxidase expression and function. In
      monocytic and microglial cell lines, the expression of the NADPH oxidase subunit
      gp91(phox) was induced by lipopolysaccharide/interferon gamma treatment and was
      inhibited in cells constitutively expressing IkappaBalpha. Furthermore, inducible
      reactive oxygen species production was inhibited in IkappaBalpha overexpressing
      cells. gp91(phox) expression was very low in RelA(-/-) fibroblasts and could be
      induced by reconstituting these cells with p65/RelA. Thus, gp91(phox) expression
      is dependent on the presence of p65/RelA. We also found that gp91(phox)
      transcription is dependent on NF-kappaB and we identified two potential cis
      acting elements in the murine gp91(phox) promoter that control NF-kappaB
      dependent regulation. The findings raise the possibility of a positive feedback
      loop in which NF-kappaB activation by oxidative stress leads to further radical
      production via NADPH oxidase.

PMID- 16407284
TI  - Blockade of NFAT activation by the second calcineurin binding site.
AB  - Activation of NFAT transcription factors requires their dephosphorylation by the
      phosphatase calcineurin (CN). NFATs contain two CN binding motifs: PxIxIT and
      CnBP-B/CNBR2 (which we call LxVP). Here we carry out a detailed comparative
      analysis of the CN binding activity displayed by the PxIxIT and LxVP sites from
      different NFATs. Dose-response CN binding experiments with GST fusion proteins of
      NFATc1 and NFATc2 showed that NFATc1 binds CN in vitro more efficiently than does
      NFATc2. This difference in binding appears to be caused by the different CN
      binding potencies of the corresponding LxVP sites; thus while the LxVPc2 peptide
      fused to GST did not bind CN, GST-LxVPc1 bound it more efficiently than did GST
      PxIxITc1 or GST-PxIxITc2. Furthermore, an NFATc2 chimera protein containing the
      LxVP motif from NFATc1 interacted with CN much more potently than did wild-type
      NFATc2. Free peptides spanning the LxVP motifs from NFATc1, c3 or c4 displaced CN
      from GST-NFATc1 and GST-NFATc2 more efficiently than any PxIxIT peptide. PxIxITc2
      and LxVPc1 peptides were each able to cross-compete GST-LxVPc1-CN and GST
      PxIxITc2-CN binding. In contrast with PxIxITc2, the LxVP peptide not only blocked
      CN-NFAT binding but also inhibited CN phosphatase activity in vitro. Furthermore,
      exogenous LxVPc1 blocked NFATc2 phosphorylation and nuclear translocation in
      vivo. These results suggest a model in which the different CN binding
      characteristics of the PxIxIT and LxVP sites enable different NFAT members to
      influence each others activities in cells where they are co-expressed.

PMID- 16407285
TI  - WARP is a novel multimeric component of the chondrocyte pericellular matrix that
      interacts with perlecan.
AB  - WARP is a novel member of the von Willebrand factor A domain superfamily of
      extracellular matrix proteins that is expressed by chondrocytes. WARP is
      restricted to the presumptive articular cartilage zone prior to joint cavitation
      and to the articular cartilage and fibrocartilaginous elements in the joint,
      spine, and sternum during mouse embryonic development. In mature articular
      cartilage, WARP is highly specific for the chondrocyte pericellular
      microenvironment and co-localizes with perlecan, a prominent component of the
      chondrocyte pericellular region. WARP is present in the guanidine-soluble
      fraction of cartilage matrix extracts as a disulfide-bonded multimer, indicating
      that WARP is a strongly interacting component of the cartilage matrix. To
      investigate how WARP is integrated with the pericellular environment, we studied
      WARP binding to mouse perlecan using solid phase and surface plasmon resonance
      analysis. WARP interacts with domain III-2 of the perlecan core protein and the
      heparan sulfate chains of the perlecan domain I with K(D) values in the low
      nanomolar range. We conclude that WARP forms macromolecular structures that
      interact with perlecan to contribute to the assembly and/or maintenance of
      "permanent" cartilage structures during development and in mature cartilages.

PMID- 16407286
TI  - Modulation of the transforming growth factor-beta signal transduction pathway by
      hepatitis C virus nonstructural 5A protein.
AB  - Transforming growth factor-beta (TGF-beta) is implicated in the pathogenesis of
      liver disease. TGF-beta is involved both in liver regeneration and in the
      fibrotic and cirrhotic transformation with hepatitis viral infection. Hepatitis C
      virus (HCV) infection often leads to cirrhosis and hepatocellular carcinoma. HCV
      nonstructural 5A (NS5A) protein is a multifunctional protein that modulates
      cytokine-mediated signal transduction pathways. To elucidate the molecular
      mechanism of HCV pathogenesis, we examined the effect of NS5A protein on TGF-beta
      stimulated signaling cascades. We show that NS5A protein inhibited the TGF-beta
      mediated signaling pathway in hepatoma cell lines as determined by reporter gene
      assay. To further investigate the role of NS5A, we examined the protein/protein
      interaction between NS5A and TGF-beta signal transducers. Both in vitro and in
      vivo binding data showed that NS5A protein directly interacted with TGF-beta
      receptor I (TbetaR-I) in hepatoma cell lines. This interaction was mapped to
      amino acids 148-238 of NS5A. We also found that NS5A protein co-localized with
      TbetaR-I in the cytoplasm of Huh7 cells and inhibited TGF-beta-mediated nuclear
      translocation of Smad2. Furthermore, we demonstrate that NS5A protein abrogated
      the phosphorylation of Smad2 and the heterodimerization of Smad3 and Smad4. To
      further explore the relevance to viral infection, we examined the effect of the
      HCV subgenomic replicon on the TGF-beta signaling pathway. We show that the HCV
      subgenomic replicon also inhibited TGF-beta-induced signaling cascades. These
      results indicate that HCV NS5A modulates TGF-beta signaling through interaction
      with TbetaR-I and that NS5A may be an important risk factor in HCV-associated
      liver pathogenesis.

PMID- 16407287
TI  - A long N-terminal-extended nested set of abundant and antigenic major
      histocompatibility complex class I natural ligands from HIV envelope protein.
AB  - Viral antigens complexed with major histocompatibility complex (MHC) class I
      molecules are recognized by cytotoxic T lymphocytes on infected cells. Assays
      with synthetic peptides identify optimal MHC class I ligands often used for
      vaccines. However, when natural peptides are analyzed, more complex mixtures
      including long peptides bulging in the middle of the binding site or with
      carboxyl extensions are found, reflecting lack of exposure to carboxypeptidases
      in the antigen processing pathway. In contrast, precursor peptides are exposed to
      extensive cytosolic aminopeptidase activity, and fewer than 1% survive, only to
      be further trimmed in the endoplasmic reticulum. We show here a striking example
      of a nested set of at least three highly antigenic and similarly abundant natural
      MHC class I ligands, 15, 10, and 9 amino acids in length, derived from a single
      human immunodeficiency virus gp160 epitope. Antigen processing, thus, gives rise
      to a rich pool of possible ligands from which MHC class I molecules can choose.
      The natural peptide set includes a 15-residue-long peptide with unprecedented 6 N
      terminal residues that most likely extend out of the MHC class I binding groove.
      This 15-mer is the longest natural peptide known recognized by cytotoxic T
      lymphocytes and is surprisingly protected from aminopeptidase trimming in living
      cells.

PMID- 16407288
TI  - Human arsenic methyltransferase (AS3MT) pharmacogenetics: gene resequencing and
      functional genomics studies.
AB  - Arsenic contaminates ground water worldwide. Methylation is an important reaction
      in the biotransformation of arsenic. We set out to study the pharmacogenetics of
      human arsenic methyltransferase (AS3MT, previously CYT19). After cloning the
      human AS3MT cDNA, we annotated the human gene and resequenced its 5'-flanking
      region, exons, and splice junctions using 60 DNA samples from African-American
      (AA) and 60 samples from Caucasian-American (CA) subjects. We observed 26 single
      nucleotide polymorphisms (SNPs), including 3 non-synonymous cSNPs, as well as a
      variable number of tandem repeats in exon 1 within an area encoding the cDNA 5'
      untranslated region. The nonsynonymous cSNPs included T860C (M287T) with
      frequencies of 10.8 and 10% in AA and CA subjects, respectively, as well as C517T
      (A173W) in one AA and C917T (T306I) in one CA sample. Haplotype analysis showed
      that Ile(306) was linked to Thr(287), so this double variant allozyme was also
      studied functionally. After expression in COS-1 cells and correction for
      transfection efficiency, the Trp(173) allozyme displayed 31%, Thr(287) 350%,
      Ile(306) 4.8%, and Thr(287)/Ile(306) 6.2% of the activity of the wild type (WT)
      allozyme, with 20, 190, 4.4, and 7.9% of the level of WT immunoreactive protein,
      respectively. Apparent K(m) values for S-adenosyl-l-methionine were 4.6, 3.1, and
      11 mum for WT, Trp(173), and Thr(287) allozymes, with K(m) values for sodium
      arsenite with the same allozymes of 11.8, 8.9, and 4.5mum. The Ile(306) and
      Thr(287)/Ile(306) allozymes expressed too little activity for inclusion in the
      substrate kinetic studies. Expression of reporter gene constructs for the 5'
      flanking region and the variable number of tandem repeats in the 5'-untranslated
      region demonstrated cell line-dependent variation in reporter gene expression,
      with shorter repeats associated with increased transcription in HepG2 cells.
      These results raise the possibility that inherited variation in AS3MT may
      contribute to variation in arsenic metabolism and, perhaps, arsenic-dependent
      carcinogenesis in humans.

PMID- 16407289
TI  - Regulation of the composition of the extracellular matrix by low density
      lipoprotein receptor-related protein-1: activities based on regulation of mRNA
      expression.
AB  - Low density lipoprotein receptor-related protein-1 (LRP-1) is a catabolic
      receptor for extracellular matrix (ECM) structural proteins and for proteins that
      bind to ECM. LRP-1 also is implicated in integrin maturation. In this study, we
      applied a proteomics strategy to identify novel proteins involved in ECM modeling
      that are regulated by LRP-1. We show that LRP-1 deficiency in murine embryonic
      fibroblasts (MEFs) is associated with increased levels of type III collagen and
      pigment epithelium-derived factor, which accumulate in the substratum surrounding
      cells. The collagen receptor, uPAR-AP/Endo-180, is also increased in LRP-1
      deficient MEFs. Human LRP-1 reversed the changes in protein expression associated
      with LRP-1 deficiency; however, the endocytic activity of LRP-1 was not involved.
      Instead, regulation occurred at the mRNA level. Inhibition of c-Jun amino
      terminal kinase (JNK) blocked type III collagen expression in LRP-1-deficient
      MEFs, suggesting regulation of JNK activity as a mechanism by which LRP-1
      controls mRNA expression. The ability of LRP-1 to regulate expression of the
      factors identified here suggests a role for LRP-1 in determining blood vessel
      structure and in angiogenesis.

PMID- 16407290
TI  - Conformation-assisted inhibition of protein-tyrosine phosphatase-1B elicits
      inhibitor selectivity over T-cell protein-tyrosine phosphatase.
AB  - PTP-1B represents an attractive target for the treatment of type 2 diabetes and
      obesity. Given the role that protein phosphatases play in the regulation of many
      biologically relevant processes, inhibitors against PTP-1B must be not only
      potent, but also selective. It has been extremely difficult to synthesize
      inhibitors that are selective over the highly homologous TCPTP. We have
      successfully exploited the conservative Leu119 to Val substitution between the
      two enzymes to synthesize a PTP-1B inhibitor that is an order of magnitude more
      selective over TCPTP. Structural analyses of PTP-1B/inhibitor complexes show a
      conformation-assisted inhibition mechanism as the basis for selectivity. Such an
      inhibitory mechanism may be applicable to other homologous enzymes.

PMID- 16407291
TI  - Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation
      of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53.
AB  - Endoplasmic reticulum (ER) stress-induced apoptosis has been implicated in the
      development of multiple diseases. However, the in vivo signaling pathways are
      still not fully understood. In this report, through the use of genetically
      deficient mouse embryo fibroblasts (MEFs) and their matched wild-type controls,
      we have demonstrated that the mitochondrial apoptotic pathway mediated by Apaf-1
      is an integral part of ER stress-induced apoptosis and that ER stress activates
      different caspases through Apaf-1-dependent and -independent mechanisms. In
      search of the molecular link between ER stress and the mitochondrial apoptotic
      pathway, we have discovered that in MEFs, ER stress selectively activates BH3
      only proteins PUMA and NOXA at the transcript level through the tumor suppressor
      gene p53. In p53(-/-) MEFs, ER stress-induced apoptosis is partially suppressed.
      The p53-independent apoptotic pathway may be mediated by C/EBP homologous protein
      (CHOP) and caspase-12, as their activation is intact in p53(-/-) MEFs. In
      multiple MEF lines, p53 is primarily nuclear and its level is elevated upon ER
      stress. To establish the role of NOXA and PUMA in ER stress-induced apoptosis, we
      have shown that, in MEFs deficient in NOXA or PUMA, ER stress-induced apoptosis
      is reduced. Reversibly, overexpression of NOXA or PUMA induces apoptosis as
      evidenced by the activation of BAK and caspase-7. Our results provide new
      evidence that, in MEFs, in addition to PUMA, p53 and NOXA are novel components of
      the ER stress-induced apoptotic pathway, and both contribute to ER stress-induced
      apoptosis.

PMID- 16407292
TI  - Hepatic PCSK9 expression is regulated by nutritional status via insulin and
      sterol regulatory element-binding protein 1c.
AB  - Familial autosomal dominant hypercholesterolemia is associated with high risk for
      cardiovascular accidents and is related to mutations in the low density
      lipoprotein receptor or its ligand apolipoprotein B (apoB). Mutations in a third
      gene, proprotein convertase subtilisin kexin 9 (PCSK9), were recently associated
      to this disease. PCSK9 acts as a natural inhibitor of the low density lipoprotein
      receptor pathway, and both genes are regulated by depletion of cholesterol cell
      content and statins, via sterol regulatory element-binding protein (SREBP). Here
      we investigated the regulation of PCSK9 gene expression during nutritional
      changes. We showed that PCSK9 mRNA quantity is decreased by 73% in mice after 24
      h of fasting, leading to a 2-fold decrease in protein level. In contrast PCSK9
      expression was restored upon high carbohydrate refeeding. PCSK9 mRNA increased by
      4-5-fold in presence of insulin in rodent primary hepatocytes, whereas glucose
      had no effect. Moreover, insulin up-regulated hepatic PCSK9 expression in vivo
      during a hyperinsulinemic-euglycemic clamp in mice. Adenoviral mediated
      overexpression of a dominant or negative form of SREBP-1c confirmed the
      implication of this transcription factor in insulin-mediated stimulation of PCSK9
      expression. Liver X receptor agonist T0901317 also regulated PCSK9 expression via
      this same pathway (a 2-fold increase in PCSK9 mRNA of primary hepatocytes
      cultured for 24 h in presence of 1 microm T0901317). As our last investigation,
      we isolated PCSK9 proximal promoter and verified the functionality of a SREBP-1c
      responsive element located from 335 bp to 355 bp upstream of the ATG. Together,
      these results show that PCSK9 expression is regulated by nutritional status and
      insulinemia.

PMID- 16407293
TI  - Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta
      catenin but not bone morphogenetic protein signaling.
AB  - Notch proteins are transmembrane receptors that control cell-fate decisions. Upon
      ligand binding, Notch receptors undergo proteolytic cleavage leading to the
      release of their intracellular domain (NICD). Overexpression of NICD impairs
      osteoblastogenesis, but the mechanisms are not understood. We examined
      consequences of the constitutive activation of Notch 1 in ST-2 cells. Notch
      opposed the effects of bone morphogenetic protein (BMP)-2 and Wnt 3a on alkaline
      phosphatase activity (APA). BMP-2 induced the phosphorylation of Smad 1/5/8 and
      the transactivation of a BMP/Smad-responsive construct (12xSBE-Oc-pGL3), but the
      effect was not modified by Notch. BMP-2 had minimal effects on the
      phosphorylation of the mitogen-activated protein kinases ERK, p38, and JNK, in
      the absence or presence of NICD. Notch overexpression decreased the
      transactivating effect of Wnt 3a, cytoplasmic beta-catenin levels, and Wnt
      dependent gene expression. Transfection of a mutant beta-catenin expression
      construct, or the use of a glycogen synthase kinase 3beta inhibitor to stabilize
      beta-catenin, partially blocked the inhibitory effect of NICD on Wnt signaling
      and on APA. HES-1 or Groucho1/TLE1 RNA interference enhanced basal and induced
      Wnt/beta-catenin signaling opposing NICD effects, but only HES-1 silencing
      enhanced Wnt 3a effects on APA. In conclusion, NICD overexpression prevents BMP-2
      and Wnt biological effects by suppressing Wnt but not BMP signaling. HES-1
      appears to mediate effects of Notch on osteoblastogenesis.

PMID- 16407294
TI  - Identification and characterization of murine SCARA5, a novel class A scavenger
      receptor that is expressed by populations of epithelial cells.
AB  - Epithelia are positioned at a critical interface to prevent invasion by
      microorganisms from the environment. Pattern recognition receptors are important
      components of innate immunity because of their ability to interact with specific
      microbe-associated structures and initiate immune responses. Several distinct
      groups of receptors have been recognized. One of these, the scavenger receptors,
      has been classified into at least eight separate classes. The class A scavenger
      receptors are characterized by the presence of a collagen-like domain and include
      macrophage scavenger receptor type A (SR-A1 I/II, SCARA1) and MARCO (SCARA2).
      These receptors are known to make important contributions to host defense. Here,
      we identify a novel murine scavenger receptor, SCARA5, which has a structure
      typical of this class. The cDNA encodes 491 amino acids, which predict a type II
      protein that contains C-terminal intracellular, transmembrane, extracellular
      spacer, collagenous, and N-terminal scavenger receptor cysteine rich domains.
      Expression in Chinese hamster ovary cells confirmed that the receptor assembles
      as a homotrimer and is expressed at the plasma membrane. SCARA5-transfected cells
      bound Escherichia coli and Staphylococcus aureus, but not zymosan, in a
      polyanionic-inhibitable manner. Unlike other class A scavenger receptors, the
      receptor was unable to endocytose acetylated or oxidized low density lipoprotein.
      Quantitative RT-PCR and in situ hybridization demonstrate SCARA5 has a tissue and
      cellular distribution unique among class A scavenger receptors. Because of the
      restriction of SCARA5 transcripts to populations of epithelial cells, we propose
      that this receptor may play important roles in the innate immune activities of
      these cells.

PMID- 16407295
TI  - Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2
      expression in macrophages by the beta-glucan receptor.
AB  - Phagocytosis of non-opsonized microorganisms by macrophages initiates innate
      immune responses for host defense against infection. Cytosolic phospholipase A(2)
      is activated during phagocytosis, releasing arachidonic acid for production of
      eicosanoids, which initiate acute inflammation. Our objective was to identify
      pattern recognition receptors that stimulate arachidonic acid release and
      cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast
      cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release
      from resident mouse peritoneal macrophages was blocked by soluble glucan
      phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and
      prostaglandin production were enhanced by overexpressing the beta-glucan
      receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure
      particulate (1, 3)-beta-D-glucan stimulated arachidonic acid release and COX2
      expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent
      manner by macrophage-activating lipopeptide-2. However, arachidonic acid release
      and leukotriene C(4) production stimulated by zymosan and C. albicans were TLR2
      independent, whereas COX2 expression and prostaglandin production were partially
      blunted in TLR2(-/-) macrophages. Inhibition of Syk tyrosine kinase blocked
      arachidonic acid release and COX2 expression in response to zymosan, C. albicans,
      and particulate (1, 3)-beta-D-glucan. The results suggest that cytosolic
      phospholipase A(2) activation triggered by the beta-glucan component of yeast is
      dependent on the immunoreceptor tyrosine-based activation motif-like domain of
      dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate
      COX2 expression.

PMID- 16407296
TI  - Mitochondrial and nuclear forms of Wnt13 are generated via alternative promoters,
      alternative RNA splicing, and alternative translation start sites.
AB  - Wnt proteins play a key role in cell survival, cell proliferation, and cell fate
      during development. In endothelial cells, we identified the expression of Wnt13A,
      Wnt13B, and Wnt13C mRNAs, which are generated by alternative promoters and
      alternative RNA splicing. Wnt13A and Wnt13B proteins differ only in their N
      terminal sequences. Wnt13A, a typical Wnt, is N-glycosylated and localized in the
      endoplasmic reticulum, with only a small fraction being secreted. Wnt13B proteins
      appear as a protein doublet, L-Wnt13B and S-Wnt13B, which are neither N
      glycosylated nor secreted. Wnt13B proteins localized mainly to mitochondria, as
      demonstrated using detection in mitochondria enriched fractions and
      colocalization with Mitotracker and HSP60. A nuclear localization was also
      observed in 20% of Wnt13B-expressing cells. Both the N-terminal hydrophobic
      stretch (residues 1-17) and alpha-helix (residues 26-50) were the main
      determinants for Wnt13B mitochondrial targeting. Serial deletions of Wnt13B N
      terminal sequences abolished its association with mitochondria and favored
      instead a nuclear localization. The production of S-Wnt13B was independent of the
      mitochondrial targeting but dependent on an alternative translation start
      corresponding to Met(74) in L-Wnt13B. The same translation start is used in
      Wnt13C mRNA to encode a protein undistinguishable from S-Wnt13B. S-Wnt13B when
      expressed alone localized to the nucleus like Wnt13C, whereas L-Wnt13B localized
      to mitochondria. Wnt13 nuclear forms increased the beta-catenin/T-cell factor
      activity in HEK293 cells and increased apoptosis in bovine aortic endothelial
      cells. Altogether our results demonstrate that, in addition to alternative
      promoters and RNA splicing, an alternative translation start in Wnt13B and Wnt13C
      mRNAs increases the complexity of both human wnt13 expression and functions.

PMID- 16407297
TI  - Four and a half LIM protein 1 binds myosin-binding protein C and regulates myosin
      filament formation and sarcomere assembly.
AB  - Four and a half LIM protein 1 (FHL1/SLIM1) is highly expressed in skeletal and
      cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid
      screening identified slow type skeletal myosin-binding protein C as an FHL1
      binding partner. Myosin-binding protein C is the major myosin-associated protein
      in striated muscle that enhances the lateral association and stabilization of
      myosin thick filaments and regulates actomyosin interactions. The interaction
      between FHL1 and myosin-binding protein C was confirmed using co
      immunoprecipitation of recombinant and endogenous proteins. Recombinant FHL2 and
      FHL3 also bound myosin-binding protein C. FHL1 impaired co-sedimentation of
      myosin-binding protein C with reconstituted myosin filaments, suggesting FHL1 may
      compete with myosin for binding to myosin-binding protein C. In intact skeletal
      muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and
      sarcolemma, co-localizing with myosin-binding protein C at the sarcolemma in
      intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the
      M-line appeared to extend partially into the C-zone of the A-band, where it co
      localized with myosin-binding protein C. Overexpression of FHL1 in
      differentiating C2C12 cells induced "sac-like" myotube formation (myosac),
      associated with impaired Z-line and myosin thick filament assembly. This
      phenotype was rescued by co-expression of myosin-binding protein C. FHL1
      knockdown using RNAi resulted in impaired myosin thick filament formation
      associated with reduced incorporation of myosin-binding protein C into the
      sarcomere. This study identified FHL1 as a novel regulator of myosin-binding
      protein C activity and indicates a role for FHL1 in sarcomere assembly.

PMID- 16407298
TI  - A nuclear transport signal in mammalian target of rapamycin is critical for its
      cytoplasmic signaling to S6 kinase 1.
AB  - The mammalian target of rapamycin (mTOR) regulates nutrient-dependent cell growth
      and proliferation through cytoplasmic targets, such as S6 kinase 1 (S6K1).
      Consistent with its main function in the cytoplasm, mTOR is predominantly
      cytoplasmic. However, previously we have found that mTOR shuttles between the
      nucleus and cytoplasm, and we have proposed that the nucleocytoplasmic shuttling
      of mTOR is required for the maximal activation of S6K1. The intrinsic signals
      directing mTOR nuclear transport and the underlying mechanisms are unknown. In
      this study we initially set out to identify nuclear export signals in mTOR. A
      systematic scan of the mTOR sequence revealed 16 peptides conforming to the
      canonical leucine-rich nuclear export signal, of which 3 were found by reporter
      assays to contain leptomycin B-sensitive and leucine-dependent nuclear export
      activity. Unexpectedly, mTOR proteins with those conserved leucines mutated to
      alanines were unable to enter the nucleus. Further investigation revealed that
      the L982A/L984A and L1287A/L1289A mutations likely induced a global structural
      change in mTOR, whereas the L545A/L547A mutation directly impaired the nuclear
      import of the protein, potentially regulated by a nucleocytoplasmic shuttling
      signal. The loss of nuclear import was accompanied by the significantly reduced
      ability of the L545A/L547A mutant to activate S6K1 in cells. Most importantly,
      when nuclear import was restored in the L545A/L547A mutant by the addition of an
      exogenous nuclear import signal, signaling to S6K1 was rescued. Taken together,
      our observations suggest the existence of a nuclear shuttling signal in mTOR and
      provide definitive evidence for the requirement of mTOR nuclear import in its
      cytoplasmic signaling to S6K1.

PMID- 16407299
TI  - The vinculin binding sites of talin and alpha-actinin are sufficient to activate
      vinculin.
AB  - Vinculin regulates both cell-cell and cell-matrix junctions and anchors adhesion
      complexes to the actin cytoskeleton through its interactions with the vinculin
      binding sites of alpha-actinin or talin. Activation of vinculin requires a
      severing of the intramolecular interactions between its N- and C-terminal
      domains, which is necessary for vinculin to bind to F-actin; yet how this occurs
      in cells is not resolved. We tested the hypothesis that talin and alpha-actinin
      activate vinculin through their vinculin binding sites. Indeed, we show that
      these vinculin binding sites have a high affinity for full-length vinculin, are
      sufficient to sever the head-tail interactions of vinculin, and they induce
      conformational changes that allow vinculin to bind to F-actin. Finally,
      microinjection of these vinculin binding sites specifically targets vinculin in
      cells, disrupting its interactions with talin and alpha-actinin and disassembling
      focal adhesions. In their native (inactive) states the vinculin binding sites of
      talin and alpha-actinin are buried within helical bundles present in their
      central rod domains. Collectively, these results support a model where the
      engagement of adhesion receptors first activates talin or alpha-actinin, by
      provoking structural changes that allow their vinculin binding sites to swing
      out, which are then sufficient to bind to and activate vinculin.

PMID- 16407300
TI  - The amphoterin (HMGB1)/receptor for advanced glycation end products (RAGE) pair
      modulates myoblast proliferation, apoptosis, adhesiveness, migration, and
      invasiveness. Functional inactivation of RAGE in L6 myoblasts results in tumor
      formation in vivo.
AB  - We reported that RAGE (receptor for advanced glycation end products), a
      multiligand receptor of the immunoglobulin superfamily expressed in myoblasts,
      when activated by its ligand amphoterin (HMGB1), stimulates rat L6 myoblast
      differentiation via a Cdc42-Rac-MKK6-p38 mitogen-activated protein kinase
      pathway, and that RAGE expression in skeletal muscle tissue is developmentally
      regulated. We show here that inhibition of RAGE function via overexpression of a
      signaling deficient RAGE mutant (RAGE delta cyto) results in increased myoblast
      proliferation, migration, and invasiveness, and decreased apoptosis and
      adhesiveness, whereas myoblasts overexpressing RAGE behave the opposite, compared
      with mock-transfected myoblasts. These effects are accompanied by a decreased
      induction of the proliferation inhibitor, p21(Waf1), and increased induction of
      cyclin D1 and extent of Rb, ERK1/2, and JNK phosphorylation in L6/RAGE delta cyto
      myoblasts, the opposite occurring in L6/RAGE myoblasts. Neutralization of culture
      medium amphoterin negates effects of RAGE activation, suggesting that amphoterin
      is the RAGE ligand involved in RAGE-dependent effects in myoblasts. Finally, mice
      injected with L6/RAGE delta cyto myoblasts develop tumors as opposed to mice
      injected with L6/RAGE or L6/mock myoblasts that do not. Thus, the amphoterin/RAGE
      pair stimulates myoblast differentiation by the combined effect of stimulation of
      differentiation and inhibition of proliferation, and deregulation of RAGE
      expression in myoblasts might contribute to their neoplastic transformation.

PMID- 16407301
TI  - Phosphorylation of serine 526 is required for MEKK3 activity, and association
      with 14-3-3 blocks dephosphorylation.
AB  - MAPK/ERK kinase kinase 3 (MEKK3) is a mitogen-activated protein kinase kinase
      kinase (MAP3K) that functions upstream of the MAP kinases and IkappaB kinase.
      Phosphorylation is believed to be a critical component for MEKK3-dependent signal
      transduction, but little is known about the phosphorylation sites of this MAP3K.
      To address this question, point mutations were introduced in the activation loop
      (T-loop), substituting alanine for serine or threonine, and the mutants were
      transfected into HEK293 Epstein-Barr virus nuclear antigen cells. MEKK3-dependent
      activation of an NF-kappaB reporter gene as well as ERK, JNK, and p38 MAP kinases
      correlated with a requirement for serine at position 526. Constitutively active
      mutants of MEKK3, consisting of S526D and S526E, were capable of activating a NF
      kappaB luciferase reporter gene as well as ERK and MEK, suggesting that a
      negative charge at Ser526 was necessary for MEKK3 activity and implicating Ser526
      as a phosphorylation site. An antibody was developed that specifically recognized
      phospho-Ser526 of MEKK3 but did not recognize the S526A point mutant. The
      catalytically inactive (K391M) mutant of MEKK3 was not phosphorylated at Ser526,
      indicating that phosphorylation of Ser526 occurs via autophosphorylation.
      Endogenous MEKK3 was phosphorylated on Ser526 in response to osmotic stress. In
      addition, phosphorylation of Ser526 was required for MKK6 phosphorylation in
      vitro, whereas dephosphorylation of Ser526 was mediated by protein phosphatase 2A
      and sensitive to okadaic acid and sodium fluoride. Finally, the association
      between MEKK3 and 14-3-3 was dependent on Ser526 and prevented dephosphorylation
      of Ser526. In summary, Ser526 of MEKK3 is an autophosphorylation site within the
      T-loop that is regulated by PP2A and 14-3-3 proteins.

PMID- 16407302
TI  - The activity of the vinculin binding sites in talin is influenced by the
      stability of the helical bundles that make up the talin rod.
AB  - The talin rod contains approximately 11 vinculin binding sites (VBSs), each
      defined by hydrophobic residues in a series of amphipathic helices that are
      normally buried within the helical bundles that make up the rod. Consistent with
      this, talin failed to compete for binding of the vinculin Vd1 domain to an
      immobilized talin polypeptide containing a constitutively active VBS. However,
      talin did bind to GST-Vd1 in pull-down assays, and isothermal titration
      calorimetry measurements indicate a K(d) of approximately 9 mum. Interestingly,
      Vd1 binding exposed a trypsin cleavage site in the talin rod between residues 898
      and 899, indicating that there are one or more active VBSs in the N-terminal part
      of the talin rod. This region comprises a five helix bundle (residues 482-655)
      followed by a seven-helix bundle (656-889) and contains five VBSs (helices 4, 6,
      9, 11, and 12). The single VBS within 482-655 is cryptic at room temperature. In
      contrast, talin 482-889 binds Vd1 with high affinity (K(d) approximately 0.14
      mum), indicating that one or more of the four VBSs within 656-889 are active, and
      this likely represents the vinculin binding region in intact talin. In support of
      this, hemagglutinin-tagged talin 482-889 localized efficiently to focal
      adhesions, whereas 482-655 did not. Differential scanning calorimetry showed a
      strong negative correlation between Vd1 binding and helical bundle stability, and
      a 755-889 mutant with a more stable fold bound Vd1 much less well than wild type.
      We conclude that the stability of the helical bundles that make up the talin rod
      is an important factor determining the activity of the individual VBSs.

PMID- 16407303
TI  - The RNA-binding PUA domain of archaeal tRNA-guanine transglycosylase is not
      required for archaeosine formation.
AB  - Bacterial tRNA-guanine transglycosylase (TGT) replaces the G in position 34 of
      tRNA with preQ(1), the precursor to the modified nucleoside queuosine. Archaeal
      TGT, in contrast, substitutes preQ(0) for the G in position 15 of tRNA as the
      first step in archaeosine formation. The archaeal enzyme is about 60% larger than
      the bacterial protein; a carboxyl-terminal extension of 230 amino acids contains
      the PUA domain known to contact the four 3'-terminal nucleotides of tRNA. Here we
      show that the C-terminal extension of the enzyme is not required for the
      selection of G15 as the site of base exchange; truncated forms of Pyrococcus
      furiosus TGT retain their specificity for guanine exchange at position 15.
      Deletion of the PUA domain causes a 4-fold drop in the observed k(cat) (2.8 x 10(
      3) s(-1)) and results in a 75-fold increased K(m) for tRNA(Asp)(1.2 x 10(-5) m)
      compared with full-length TGT. Mutations in tRNA(Asp) altering or abolishing
      interactions with the PUA domain can compete with wild-type tRNA(Asp) for binding
      to full-length and truncated TGT enzymes. Whereas the C-terminal domains do not
      appear to play a role in selection of the modification site, their relevance for
      enzyme function and their role in vivo remains to be discovered.

PMID- 16407304
TI  - The catalytic histidine dyad of high density lipoprotein-associated serum
      paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density
      lipoprotein oxidation and stimulation of macrophage cholesterol efflux.
AB  - High density lipoprotein (HDL)-associated paraoxonase-1 (PON1) anti-atherogenic
      properties in macrophages, i.e. inhibition of cell-mediated oxidation of low
      density lipoprotein (LDL) and stimulation of cholesterol efflux, were studied
      using recombinant variants of PON1 and apoA-I expressed in Escherichia coli and
      reconstituted HDL (rHDL) particles composed of phosphatidylcholine/free
      cholesterol (PC/FC) and apoA-I. PON1 lactonase activity is stimulated by apoA-I
      by approximately 7-fold relative to PC/FC particles. Wild-type (WT) PON1 bound to
      rHDL inhibited macrophage-mediated LDL oxidation and stimulated cholesterol
      efflux from the cells to 2.3- and 3.2-fold greater extents, respectively,
      compared with WT PON1 bound to PC/FC particles without apoA-I. We also tested
      PON1 catalytic histidine dyad mutants (H115Q and H134Q) that are properly folded
      and that bind HDL in a similar mode compared with WT PON1, but that exhibit
      almost no lactonase activity. These could not inhibit macrophage-mediated LDL
      oxidation or stimulate rHDL-mediated cholesterol efflux from the cells.
      Furthermore, whereas HDL-bound WT PON1 induced the formation of
      lysophosphatidylcholine (LPC) in macrophages, the His dyad mutants did not,
      suggesting that the above anti-atherogenic properties of HDL-associated PON1
      involve LPC release. Indeed, enrichment of macrophages with increasing
      concentrations of LPC resulted in inhibition of the cells' capability to oxidize
      LDL and in stimulation of HDL-mediated cholesterol efflux from the macrophages in
      an LPC dose-dependent manner. Thus, we provide the first direct indication that
      the anti-atherogenic properties of PON1 are related to its lipolactonase activity
      and propose a model in which PON1 acts as a lipolactonase to break down oxidized
      lipids and to generate LPC.

PMID- 16407305
TI  - The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian
      serum paraoxonases.
AB  - Serum paraoxonases (PONs) are calcium-dependent lactonases that catalyze the
      hydrolysis and formation of a variety of lactones, with a clear preference for
      lipophilic lactones. However, the lactonase mechanism of mammalian PON1, a high
      density lipoprotein-associated enzyme that is the most studied family member,
      remains unclear, and other family members have not been examined at all. We
      present a kinetic and site-directed mutagenesis study aimed at deciphering the
      lactonase mechanism of PON1 and PON3. The pH-rate profile determined for the
      lactonase activity of PON1 indicated an apparent pK(a) of approximately 7.4. We
      thus explored the role of all amino acids in the PON1 active site that are not
      directly ligated to the catalytic calcium and that possess an imidazolyl or
      carboxyl side chain (His(115), His(134), His(184), His(285), Asp(183), and
      Asp(269)). Extensive site-directed mutagenesis studies in which each amino acid
      candidate was replaced with all other 19 amino acids were conducted to identify
      the residue(s) that mediate the lactonase activity of PONs. The results indicate
      that the lactonase activity of PON1 and PON3 and the esterase activity of PON1
      are mediated by the His(115)-His(134) dyad. Notably, the phosphotriesterase
      activity of PON1, which is a promiscuous activity of this enzyme, is mediated by
      other residues. To our knowledge, this is one of few examples of a histidine dyad
      in enzyme active sites and the first example of a hydrolytic enzyme with such a
      dyad.

PMID- 16407307
TI  - Modulation of Streptomyces leucine aminopeptidase by calcium: identification and
      functional analysis of key residues in activation and stabilization by calcium.
AB  - Streptomyces griseus leucine aminopeptidase (SGAP), which has two zinc atoms in
      its active site, is clinically important as a model for understanding the
      structure and mechanism of action of other metallopeptidases. SGAP is a calcium
      activated and calcium-stabilized enzyme, and its activation by calcium correlates
      with substrate specificity. In our previous study, we found a non-calcium
      modulated leucine aminopeptidase secreted by Streptomyces septatus, the primary
      structure of which showed 71% identity with SGAP. In this study, we constructed
      chimeras of SGAP and S. septatus aminopeptidase by using an in vivo DNA shuffling
      system and several mutant enzymes by site-directed mutagenesis to identify the
      key residues in this modulation by calcium. We identified the key residues Asp
      173 and Asp-174 of SGAP associated with both SGAP activation and stabilization by
      calcium. We also showed that the known calcium-binding site, which is composed of
      Asp-3, Ile-4, Asp-262, and Asp-266 of SGAP, only contributes to SGAP
      stabilization by calcium. Furthermore, we identified an important residue, Glu
      196, that functions in cooperation with Asp-173, Asp-174, and calcium to increase
      the catalytic activity of SGAP.

PMID- 16407306
TI  - AtGAT1, a high affinity transporter for gamma-aminobutyric acid in Arabidopsis
      thaliana.
AB  - Functional characterization of Arabidopsis thaliana GAT1 in heterologous
      expression systems, i.e. Saccharomyces cerevisiae and Xenopus laevis oocytes,
      revealed that AtGAT1 (At1g08230) codes for an H(+)-driven, high affinity gamma
      aminobutyric acid (GABA) transporter. In addition to GABA, other omega-aminofatty
      acids and butylamine are recognized. In contrast to the most closely related
      proteins of the proline transporter family, proline and glycine betaine are not
      transported by AtGAT1. AtGAT1 does not share sequence similarity with any of the
      non-plant GABA transporters described so far, and analyses of substrate
      selectivity and kinetic properties showed that AtGAT1-mediated transport is
      similar but distinct from that of mammalian, bacterial, and S. cerevisiae GABA
      transporters. Consistent with a role in GABA uptake into cells, transient
      expression of AtGAT1/green fluorescent protein fusion proteins in tobacco
      protoplasts revealed localization at the plasma membrane. In planta, AtGAT1
      expression was highest in flowers and under conditions of elevated GABA
      concentrations such as wounding or senescence.

PMID- 16407308
TI  - Group V secretory phospholipase A2 translocates to the phagosome after zymosan
      stimulation of mouse peritoneal macrophages and regulates phagocytosis.
AB  - We have previously reported that group V secretory phospholipase A2 (sPLA2)
      amplifies the action of cytosolic phospholipase A2(cPLA2) alpha in regulating
      eicosanoid biosynthesis by mouse peritoneal macrophages stimulated with zymosan
      (Satake, Y., Diaz, B. L., Balestrieri, B., Lam, B. K., Kanaoka, Y., Grusby, M.
      J., and Arm, J. P. (2004) J. Biol. Chem. 279, 16488-16494). To further understand
      the role of group V sPLA2, we studied its localization in resting mouse
      peritoneal macrophages before and after stimulation with zymosan and the effect
      of deletion of the gene encoding group V sPLA2 on phagocytosis of zymosan. We
      report that group V sPLA2 is present in the Golgi apparatus and recycling
      endosome in the juxtanuclear region of resting peritoneal macrophages. Upon
      ingestion of zymosan by mouse peritoneal macrophages, group V sPLA2 is recruited
      to the phagosome. There it co-localizes with cPLA2alpha, 5-lipoxygenase, 5
      lipoxygenase-activating protein, and leukotriene C4 synthase. Using
      immunostaining for the cysteinyl leukotrienes in carbodiimide-fixed cells, we
      show, for the first time, that the phagosome is a site of cysteinyl leukotriene
      formation. Furthermore, peritoneal macrophages from group V sPLA2-null mice
      demonstrated a >50% attenuation in phagocytosis of zymosan particles, which was
      restored by adenoviral expression of group V sPLA2 but IIA not group sPLA2. These
      data demonstrate that group V sPLA2 contributes to the innate immune response
      both through regulation of eicosanoid generation in response to a phagocytic
      stimulus and also as a component of the phagocytic machinery.

PMID- 16407310
TI  - Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology
      via C-Jun N-terminal kinase and Rho kinase-1.
AB  - We have reported previously that human prostate-derived sterile 20-like kinase
      (PSK) 1 alters actin cytoskeletal organization and binds to microtubules,
      regulating their organization and stability. We have shown a structurally related
      protein kinase PSK2, which lacks a microtubule-binding site, activated c-Jun N
      terminal kinase (JNK), and induced apoptotic morphological changes that include
      cell contraction, membrane blebbing, and apoptotic body formation. Apoptotic
      stimuli increased the catalytic activity of endogenous PSK2 and JNK, and dominant
      negative JNK or a physiological inhibitor of JNK blocked these apoptotic
      morphological responses to PSK2, demonstrating a requirement for JNK. PSK2 also
      stimulated the cleavage of Rho kinase-1 (ROCK-I), and the activity of ROCK-I was
      required for PSK2 to induce cell contraction and membrane blebbing. The
      activation of caspases was also needed for the induction of membrane blebbing by
      PSK2, which was itself a substrate for caspase 3. PSK2 therefore regulates
      apoptotic morphology associated with the execution phase of apoptosis, which
      involves dynamic reorganization of the actin cytoskeleton, via downstream targets
      that include JNK and ROCK-I. Our findings suggest that PSKs form a subgroup of
      sterile 20 (STE20)-like kinases that regulate different cytoskeletal processes.

PMID- 16407309
TI  - Casein kinase II phosphorylation of the yeast phospholipid synthesis
      transcription factor Opi1p.
AB  - The transcription factor Opi1p regulates phospholipid synthesis in the yeast
      Saccharomyces cerevisiae by repressing the expression of several UAS(INO)
      containing genes (e.g. INO1). Opi1p repressor activity is most active in inositol
      supplemented cells. Regulation of Opi1p repressor activity is mediated by
      multiple phosphorylations catalyzed by protein kinases A and C. In this work, we
      showed that Opi1p was also phosphorylated by casein kinase II. Using purified
      maltose-binding protein-Opi1p as a substrate, casein kinase II activity was dose
      and time-dependent and dependent on the concentrations of maltose-binding protein
      Opi1p (Km = 25 microg/ml) and ATP (Km = 7 microM). Of three mutations (S10A,
      S38A, and S239A) in putative phosphorylation sites, 10 only the S10A mutation
      affected Opi1p phosphorylation. That Ser10 was a specific target of casein kinase
      II was confirmed by the loss of a phosphopeptide in the S10A mutant protein. The
      S10A mutation did not affect phosphorylation of Opi1p by either protein kinase A
      or protein kinase C. Likewise, phosphorylation of Opi1p by casein kinase II was
      not affected by mutations in protein kinase A (S31A and S251A) and protein (S10A)
      kinase C (S26A) phosphorylation sites. Expression of the OPI1 allele in an
      opi1Delta mutant attenuated (2-fold) the repressive effect of Opi1p on INO1
      expression, and this effect was only observed when cells were grown in the
      absence of inositol. These data supported the conclusion that casein kinase II
      phosphorylation at Ser10 played a role in stimulating the repression of INO1 when
      Opi1p was not in its most active state (i.e. in inositol-deprived cells).

PMID- 16407311
TI  - Trigger factor forms a protective shield for nascent polypeptides at the
      ribosome.
AB  - In prokaryotes, the ribosome-associated Trigger Factor is the first chaperone
      newly synthesized polypeptides encounter when they emerge from the ribosomal exit
      tunnel. The effects that Trigger Factor exerts on nascent polypeptides, however,
      remain unclear. Here we analyzed the potential of the Trigger Factor to shield
      nascent polypeptides at the ribosome. A set of arrested nascent polypeptides
      differing in origin, size, and folding status were synthesized in an Escherichia
      coli-based in vitro transcription/translation system and tested for sensitivity
      to degradation by the unspecific protease proteinase K. In the absence of Trigger
      Factor, nascent polypeptides exposed outside the ribosomal exit tunnel were
      rapidly degraded unless they were folded into a compact domain. The presence of
      Trigger Factor, as well as a Trigger Factor fragment lacking its peptidyl-prolyl
      isomerase domain, counteracted degradation of all unfolded nascent polypeptides
      tested. This protective function was specific for ribosome-tethered Trigger
      Factor, since neither non-ribosomal Trigger Factor nor the DnaK system, which
      cooperates with Trigger Factor in the folding process in vivo, revealed a
      comparable efficiency in protection. Furthermore, shielding by Trigger Factor was
      not restricted to short stretches of nascent chains but was evident for large,
      non-native nascent polypeptides exposing up to 41 kDa outside the ribosome. We
      suggest that Trigger Factor supports productive de novo folding by shielding
      nascent polypeptides on the ribosome thereby preventing untimely degradation or
      aggregation processes. This protected environment provided by Trigger Factor
      might be particularly important for large multidomain proteins to fold
      productively into their native states.

PMID- 16407312
TI  - A functional -1 ribosomal frameshift signal in the human paraneoplastic Ma3 gene.
AB  - A bioinformatics approach to finding new cases of -1 frameshifting in the
      expression of human genes revealed a classical retrovirus-like heptanucleotide
      shift site followed by a potential structural stimulator in the paraneoplastic
      antigen Ma3 and Ma5 genes. Analysis of the sequence 3' of the shift site
      demonstrated that an RNA pseudoknot in Ma3 is important for promoting efficient 
      1 frame-shifting. Ma3 is a member of a family of six genes in humans whose
      protein products contain homology to retroviral Gag proteins. The -1 frameshift
      site and pseudoknot structure are conserved in other mammals, but there are some
      sequence differences. Although the functions of the Ma genes are unknown, the
      serious neurological effects of ectopic expression in tumor cells indicate their
      importance in the brain.

PMID- 16407313
TI  - ATP hydrolysis is essential for the function of the Uup ATP-binding cassette
      ATPase in precise excision of transposons.
AB  - In Escherichia coli K-12, the RecA- and transposase-independent precise excision
      of transposons is thought to be mediated by the slippage of the DNA polymerase
      between the two short direct repeats that flank the transposon. Inactivation of
      the uup gene, encoding an ATP-binding cassette (ABC) ATPase, led to an important
      increase in the frequency of precise excision of transposons Tn10 and Tn5 and a
      defective growth of bacteriophage Mu. To provide insight into the mechanism of
      Uup in transposon excision, we purified this protein, and we demonstrated that it
      is a cytosolic ABC protein. Purified recombinant Uup binds and hydrolyzes ATP and
      undergoes a large conformational change in the presence of this nucleotide. This
      change affects a carboxyl-terminal domain of the protein that displays predicted
      structural homology with the socalled little finger domain of Y family DNA
      polymerases. In these enzymes, this domain is involved in DNA binding and in the
      processivity of replication. We show that Uup binds to DNA and that this binding
      is in part dependent on its carboxyl-terminal domain. Analysis of Walker motif B
      mutants suggests that ATP hydrolysis at the two ABC domains is strictly
      coordinated and is essential for the function of Uup in vivo.

PMID- 16407314
TI  - Consequences of ERp57 deletion on oxidative folding of obligate and facultative
      clients of the calnexin cycle.
AB  - Members of the protein-disulfide isomerase superfamily catalyze the formation of
      intra- and intermolecular disulfide bonds, a rate-limiting step of protein
      folding in the endoplasmic reticulum (ER). Here we compared maturation of one
      obligate and two facultative calnexin substrates in cells with and without ERp57,
      the calnexin-associated, glycoprotein-specific oxidoreductase. ERp57 deletion did
      not prevent the formation of disulfide bonds during co-translational
      translocation of nascent glycopolypeptides in the ER. It affected, however, the
      post-translational phases of oxidative influenza virus hemagglutinin (HA)
      folding, resulting in significant loss of folding efficiency for this obligate
      calnexin substrate. Without ERp57, HA also showed reduced capacity to recover
      from an artificially induced aberrant conformation, thus revealing a crucial role
      of ERp57 during post-translational reshuffling to the native set of HA
      disulfides. ERp57 deletion did not affect maturation of the model facultative
      calnexin substrates E1 and p62 (and of most cellular proteins, as shown by lack
      of induction of ER stress). ERp72 was identified as one of the ER-resident
      oxidoreductases associating with the orphan ERp57 substrates to maintain their
      folding competence.

PMID- 16407315
TI  - Transportin is a major nuclear import receptor for c-Fos: a novel mode of cargo
      interaction.
AB  - c-Fos, a component of the transcription factor AP-1, is rapidly imported into the
      nucleus after translation. We established an in vitro system using digitonin
      permeabilized cells to analyze nuclear import of c-Fos in detail. Two import
      receptors of the importin beta superfamily, importin beta itself and transportin,
      promote import of c-Fos in vitro. Under conditions where importin beta-dependent
      transport was blocked, c-Fos still accumulated in the nucleus in the presence of
      cytosol. Inhibition of the transportin-dependent pathway, in contrast, abolished
      import of c-Fos. Furthermore, c-Fos mutants that interact with transportin but
      not with importin beta were efficiently imported in the presence of cytosol.
      Hence, transportin appears to be the predominant import receptor for c-Fos. A
      detailed biochemical characterization revealed that the interaction of
      transportin with c-Fos is distinct from the interaction with its established
      import cargoes, the M9 sequence of heterogeneous nuclear ribonucleoprotein A1 or
      the nuclear localization sequence of some basic proteins. Likewise, the binding
      sites on importin beta for its classic import cargo and for c-Fos can be
      separated. In summary, c-Fos employs a novel mode of receptor-cargo interaction.
      Hence, transportin may be as versatile as importin beta in recognizing different
      nuclear import cargoes.

PMID- 16407316
TI  - Mitochondrial iPLA2 activity modulates the release of cytochrome c from
      mitochondria and influences the permeability transition.
AB  - The mitochondrial Ca(2+)-independent phospholipase A(2) is activated during
      energy-dependent Ca(2+) accumulation under conditions where there is a sustained
      depression of the membrane potential. This activation is not dependent on
      induction of the mitochondrial permeability transition. Bromoenol lactone, which
      inhibits the phospholipase, is effective as an inhibitor of the transition, and
      this action can be overcome by low levels of exogenous free fatty acids.
      Apparently, activation of the Ca(2+)-independent phospholipase is a factor in the
      mechanisms by which depolarization and Ca(2+) accumulation promote opening of the
      permeability transition pore. Sustained activity of the Ca(2+)-independent
      phospholipase A(2) promotes rupture of the outer mitochondrial membrane and
      spontaneous release of cytochrome c on a time scale similar to that of apoptosis
      occurring in cells. However, more swelling of the matrix space must occur to
      provoke release of a given cytochrome c fraction when the enzyme is active,
      compared with when it is inhibited. Through its effects on the permeability
      transition and release of intermembrane space proteins, the mitochondrial Ca(2+)
      independent phospholipase A(2) may be an important factor governing cell death
      caused by necrosis or apoptosis.

PMID- 16407317
TI  - Distinct hsp70 domains mediate apoptosis-inducing factor release and nuclear
      accumulation.
AB  - Although hsp70 antagonizes apoptosis-inducing factor (AIF)-mediated cell death,
      the relative importance of preventing its release from mitochondria versus
      sequestering leaked AIF in the cytosol remains controversial. To dissect these
      two protective mechanisms, hsp70 deletion mutants lacking either the chaperone
      function (hsp70-deltaEEVD) or ATPase function (hsp70-deltaATPase) were
      selectively overexpressed before exposing cells to a metabolic inhibitor, an
      insult sufficient to cause mitochondrial AIF release, nuclear AIF accumulation,
      and apoptosis. Compared with empty vector, overexpression of wild type human
      hsp70 inhibited bax activation and reduced mitochondrial AIF release after
      injury. In contrast, mutants lacking either the chaperone function (hsp70
      deltaEEVD) or the ATP hydrolytic domain (hsp70-deltaATPase) failed to prevent
      mitochondrial AIF release. Although hsp70-deltaEEVD did not inhibit bax
      activation or mitochondrial membrane injury after cell stress, this hsp70 mutant
      co-immunoprecipitated with leaked AIF in injured cells and decreased nuclear AIF
      accumulation. In contrast, hsp70-deltaATPase did not interact with AIF either in
      intact cells or in a cell-free system and furthermore, failed to prevent nuclear
      AIF accumulation. These results demonstrate that mitochondrial protection against
      bax-mediated injury requires both intact chaperone and ATPase functions, whereas
      the ATPase domain is critical for sequestering AIF in the cytosol.

PMID- 16407318
TI  - Genome-wide transcriptional dependence on TAF1 functional domains.
AB  - Transcription factor IID (TFIID) plays a central role in regulating the
      expression of most eukaryotic genes. Of the 14 TBP-associated factor (TAF)
      subunits that compose TFIID, TAF1 is one of the largest and most functionally
      diverse. Yeast TAF1 can be divided into four regions including a putative histone
      acetyltransferase domain and TBP, TAF, and promoter binding domains. Establishing
      the importance of each region in gene expression through deletion analysis has
      been hampered by the cellular requirement of TAF1 for viability. To circumvent
      this limitation we introduced galactose-inducible deletion derivatives of
      previously defined functional regions of TAF1 into a temperature-sensitive
      taf1ts2 yeast strain. After galactose induction of the TAF1 mutants and
      temperature-induced elimination of the resident Taf1ts2 protein, we examined the
      properties and phenotypes of the mutants, including their impact on genome-wide
      transcription. Virtually all TAF1-dependent genes, which comprise approximately
      90% of the yeast genome, displayed a strong dependence upon all regions of TAF1
      that were tested. This finding might reflect the need for each region of TAF1 to
      stabilize TAF1 against degradation or may indicate that all TAF1-dependent genes
      require the many activities of TAF1. Paradoxically, deletion of the region of
      TAF1 that is important for promoter binding interfered with the expression of
      many genes that are normally TFIID-independent/SAGA (Spt-Ada-Gcn5
      acetyltransferase)-dominated, suggesting that this region normally prevents TAF1
      (TFIID) from interfering with the expression of SAGA-regulated genes.

PMID- 16407319
TI  - Origin of informational polymers: differential stability of phosphoester bonds in
      ribomonomers and ribooligomers.
AB  - We have measured the stabilities of the bonds that are critical for determining
      the half-life of ribonucleotides and the beta-glycosidic and 3'- and 5'
      phosphoester bonds. Stabilities were measured under a wide range of temperatures
      and water/formamide ratios. The stability of phosphodiester bonds in
      oligoribonucleotides was determined in the same environments. The comparison of
      bond stabilities in the monomer versus the polymer forms of the ribo compounds
      revealed that physico-chemical conditions exist in which polymerization is
      thermodynamically favored. These conditions were compared with those determining
      a similar behavior for 2'-deoxyribonucleosides, deoxyribonucleotides, and
      deoxyribooligonucleotides and were shown to profoundly differ. The implications
      of these facts on the origin of informational polymers are discussed.

PMID- 16407320
TI  - BioShell--a package of tools for structural biology computations.
AB  - SUMMARY: BioShell is a suite of programs performing common tasks accompanying
      protein structure modeling. BioShell design is based on UNIX shell flexibility
      and should be used as its extension. Using BioShell various molecular modeling
      procedures can be integrated in a single pipeline. AVAILABILITY: BioShell package
      can be downloaded from its website http://biocomp.chem.uw.edu.pl/BioShell and
      these pages provide many examples and a detailed documentation for the newest
      version.

PMID- 16407321
TI  - Rapid quantitative profiling of complex microbial populations.
AB  - Diverse and complex microbial ecosystems are found in virtually every environment
      on earth, yet we know very little about their composition and ecology.
      Comprehensive identification and quantification of the constituents of these
      microbial communities--a 'census'--is an essential foundation for understanding
      their biology. To address this problem, we developed, tested and optimized a DNA
      oligonucleotide microarray composed of 10,462 small subunit (SSU) ribosomal DNA
      (rDNA) probes (7167 unique sequences) selected to provide quantitative
      information on the taxonomic composition of diverse microbial populations. Using
      our optimized experimental approach, this microarray enabled detection and
      quantification of individual bacterial species present at fractional abundances
      of <0.1% in complex synthetic mixtures. The estimates of bacterial species
      abundance obtained using this microarray are similar to those obtained by
      phylogenetic analysis of SSU rDNA sequences from the same samples--the current
      'gold standard' method for profiling microbial communities. Furthermore, probes
      designed to represent higher order taxonomic groups of bacterial species reliably
      detected microbes for which there were no species-specific probes. This simple,
      rapid microarray procedure can be used to explore and systematically characterize
      complex microbial communities, such as those found within the human body.

PMID- 16407322
TI  - A systematic approach to infer biological relevance and biases of gene network
      structures.
AB  - The development of high-throughput technologies has generated the need for
      bioinformatics approaches to assess the biological relevance of gene networks.
      Although several tools have been proposed for analysing the enrichment of
      functional categories in a set of genes, none of them is suitable for evaluating
      the biological relevance of the gene network. We propose a procedure and develop
      a web-based resource (BIOREL) to estimate the functional bias (biological
      relevance) of any given genetic network by integrating different sources of
      biological information. The weights of the edges in the network may be either
      binary or continuous. These essential features make our web tool unique among
      many similar services. BIOREL provides standardized estimations of the network
      biases extracted from independent data. By the analyses of real data we
      demonstrate that the potential application of BIOREL ranges from various
      benchmarking purposes to systematic analysis of the network biology.

PMID- 16407325
TI  - Dispersal and regulation of an adaptive mutagenesis cassette in the bacteria
      domain.
AB  - Recently, a multiple gene cassette with mutagenic translation synthesis activity
      was identified and shown to be under LexA regulation in several proteobacteria
      species. In this work, we have traced down instances of this multiple gene
      cassette across the bacteria domain. Phylogenetic analyses show that this
      cassette has undergone several reorganizations since its inception in the
      actinobacteria, and that it has dispersed across the bacterial domain through a
      combination of vertical inheritance, lateral gene transfer and duplication. In
      addition, our analyses show that LexA regulation of this multiple gene cassette
      is persistent in all the phyla in which it has been detected, and suggest that
      this regulation is prompted by the combined activity of two of its constituent
      genes: a polymerase V homolog and an alpha subunit of the DNA polymerase III.

PMID- 16407324
TI  - MaGe: a microbial genome annotation system supported by synteny results.
AB  - Magnifying Genomes (MaGe) is a microbial genome annotation system based on a
      relational database containing information on bacterial genomes, as well as a web
      interface to achieve genome annotation projects. Our system allows one to
      initiate the annotation of a genome at the early stage of the finishing phase.
      MaGe's main features are (i) integration of annotation data from bacterial
      genomes enhanced by a gene coding re-annotation process using accurate gene
      models, (ii) integration of results obtained with a wide range of bioinformatics
      methods, among which exploration of gene context by searching for conserved
      synteny and reconstruction of metabolic pathways, (iii) an advanced web interface
      allowing multiple users to refine the automatic assignment of gene product
      functions. MaGe is also linked to numerous well-known biological databases and
      systems. Our system has been thoroughly tested during the annotation of complete
      bacterial genomes (Acinetobacter baylyi ADP1, Pseudoalteromonas haloplanktis,
      Frankia alni) and is currently used in the context of several new microbial
      genome annotation projects. In addition, MaGe allows for annotation curation and
      exploration of already published genomes from various genera (e.g. Yersinia,
      Bacillus and Neisseria). MaGe can be accessed at
      http://www.genoscope.cns.fr/agc/mage.

PMID- 16407326
TI  - Evolutionary-conserved telomere-linked helicase genes of fission yeast are
      repressed by silencing factors, RNAi components and the telomere-binding protein
      Taz1.
AB  - In Schizosaccharomyces pombe the RNAi machinery and proteins mediating
      heterochromatin formation regulate the transcription of non-coding centromeric
      repeats. These repeats share a high sequence similarity with telomere-linked
      helicase (tlh) genes, implying an ancestral relationship between the two types of
      elements and suggesting that transcription of the tlh genes might be regulated by
      the same factors as centromeric repeats. Indeed, we found that mutants lacking
      the histone methyltransferase Clr4, the Pcu4 cullin, Clr7 or Clr8, accumulate
      high levels of tlh forward and reverse transcripts. Mutations and conditions
      perturbing histone acetylation had similar effects further demonstrating that the
      tlh genes are normally repressed by heterochromatin. In contrast, mutations in
      the RNAi factors Dcr1, Ago1 or Rdp1 led only to a modest derepression of the tlh
      genes indicating an alternate pathway recruits heterochromatin components to
      telomeres. The telomere-binding protein Taz1 might be part of such a redundant
      pathway, tlh transcripts being present at low levels in Deltataz1 mutants and at
      higher levels in Deltataz1 Deltadcr1 double mutants. Surprisingly, the
      chromodomain protein Chp1, a component of the Ago1-containing RITS complex,
      contributes more to tlh repression than Ago1, indicating the repressive effects
      of Chp1 are partially independent of RITS. The tlh genes are found in the
      subtelomeric regions of several other fungi raising the intriguing possibility of
      conserved regulation and function.

PMID- 16407327
TI  - APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in
      human cells.
AB  - While the ability of APOBEC3G to reduce the replication of a range of exogenous
      retroviruses is now well established, recent evidence has suggested that APOBEC3G
      can also inhibit the replication of endogenous retrotransposons that bear long
      terminal repeats. Here, we extend this earlier work by showing that two other
      members of the human APOBEC3 protein family, APOBEC3B and APOBEC3A, can reduce
      retrotransposition by the intracisternal A-particle (IAP) retrotransposon in
      human cells by 20-fold to up to 100-fold, respectively. This compares to an
      approximately 4-fold inhibition in IAP retrotransposition induced by APOBEC3G.
      While both APOBEC3G and APOBEC3B specifically interact with the IAP Gag protein
      in co-expressing cells, and induce extensive editing of IAP reverse transcripts,
      APOBEC3A fails to package detectably into IAP virus-like particles and does not
      edit IAP reverse transcripts. These data, which identify human APOBEC3A as a
      highly potent inhibitor of LTR-retrotransposon function, are the first to ascribe
      a biological activity to APOBEC3A. Moreover, these results argue that APOBEC3A
      inhibits IAP retrotransposition via a novel mechanism that is distinct from, and
      in this case more effective than, the DNA editing mechanism characteristic of
      APOBEC3G and APOBEC3B.

PMID- 16407328
TI  - High incidence of rapid telomere loss in telomerase-deficient Caenorhabditis
      elegans.
AB  - Telomerase is essential to maintain telomere length in most eukaryotes. Other
      functions for telomerase have been proposed but molecular mechanisms remain
      unclear. We studied Caenorhabditis elegans with a mutation in the trt-1
      telomerase reverse transcriptase gene. Mutant animals showed a progressive
      decrease in brood size and typically failed to reproduce after five generations.
      Using PCR analysis to measure the length of individual telomere repeat tracks on
      the left arm of chromosome V we observed that trt-1 mutants lost approximately
      125bp of telomeric DNA per generation. Chromosome fusions involving complex
      recombination reactions were observed in late generations. Strikingly, trt-1
      mutant animals displayed a high frequency of telomeres with many fewer repeats
      than average. Such outlying short telomeres were not observed in mrt-2 mutants
      displaying progressive telomere loss very similar to trt-1 mutants. We speculate
      that, apart from maintaining the average telomere length, telomerase is required
      to prevent or repair sporadic telomere truncations that are unrelated to the
      typical 'end-replication' problems.

PMID- 16407329
TI  - TBP flanking sequences: asymmetry of binding, long-range effects and consensus
      sequences.
AB  - We carried out in vitro selection experiments to systematically probe the effects
      of TATA-box flanking sequences on its interaction with the TATA-box binding
      protein (TBP). This study validates our previous hypothesis that the effect of
      the flanking sequences on TBP/TATA-box interactions is much more significant when
      the TATA box has a context-dependent DNA structure. Several interesting
      observations, with implications for protein-DNA interactions in general, came out
      of this study. (i) Selected sequences are selection-method specific and TATA-box
      dependent. (ii) The variability in binding stability as a function of the
      flanking sequences for (T-A)4 boxes is as large as the variability in binding
      stability as a function of the core TATA box itself. Thus, for (T-A)4 boxes the
      flanking sequences completely dominate and determine the binding interaction.
      (iii) Binding stabilities of all but one of the individual selected sequences of
      the (T-A)4 form is significantly higher than that of their mononucleotide-based
      consensus sequence. (iv) Even though the (T-A)4 sequence is symmetric the
      flanking sequence pattern is asymmetric. We propose that the plasticity of (T-A)n
      sequences increases the number of conformationally distinct TATA boxes without
      the need to extent the TBP contact region beyond the eight-base-pair long TATA
      box.

PMID- 16407330
TI  - Role of LrpC from Bacillus subtilis in DNA transactions during DNA repair and
      recombination.
AB  - Bacillus subtilis LrpC is a sequence-independent DNA-binding and DNA-bending
      protein, which binds both single-stranded (ss) and double-stranded (ds) DNA and
      facilitates the formation of higher order protein-DNA complexes in vitro. LrpC
      binds at different sites within the same DNA molecule promoting intramolecular
      ligation. When bound to separate molecules, it promotes intermolecular ligation,
      and joint molecule formation between a circular ssDNA and a homologous ssDNA
      tailed linear dsDNA. LrpC binding showed a higher affinity for 4-way (Holliday)
      junctions in their open conformation, when compared with curved dsDNA. Consistent
      with these biochemical activities, an lrpC null mutant strain rendered cells
      sensitive to DNA damaging agents such as methyl methanesulfonate and 4
      nitroquinoline-1-oxide, and showed a segregation defect. These findings
      collectively suggest that LrpC may be involved in DNA transactions during DNA
      repair and recombination.

PMID- 16407331
TI  - Linking uracil base excision repair and 5-fluorouracil toxicity in yeast.
AB  - 5-fluorouracil (5-FU) is a widely used anticancer drug that disrupts pyrimidine
      nucleotide pool balances and leads to uracil incorporation in DNA, which is then
      recognized and removed by the uracil base excision repair (BER) pathway. Using
      complementary biochemical and genetic approaches we have examined the role of
      uracil BER in the cell killing mechanism of 5-FU. A yeast strain lacking the
      enzyme uracil DNA glycosylase (Ung1), which excises uracil from the DNA backbone
      leaving an abasic site, showed significant protection against the toxic effects
      of 5-FU, a G1/S cell cycle arrest phenotype, and accumulated massive amounts of
      U/A base pairs in its genome (approximately 4% of T/A pairs were now U/A). A
      strain lacking the major abasic site endonuclease of Saccharomyces cerevisiae
      (Apn1) showed significantly increased sensitivity to 5-FU with G2/M arrest. Thus,
      efficient processing of abasic sites by this enzyme is protective against the
      toxic effects of 5-FU. However, contrary to expectations, the Apn1 deficient
      strain did not accumulate intact abasic sites, indicating that another repair
      pathway attempts to process these sites in the absence Apn1, but that this
      process has catastrophic effects on genome integrity. These findings suggest that
      new strategies for chemical intervention targeting BER could enhance the
      effectiveness of this widely used anticancer drug.

PMID- 16407332
TI  - Real-time observation of DNA looping dynamics of Type IIE restriction enzymes
      NaeI and NarI.
AB  - Many restriction enzymes require binding of two copies of a recognition sequence
      for DNA cleavage, thereby introducing a loop in the DNA. We investigated looping
      dynamics of Type IIE restriction enzymes NaeI and NarI by tracking the Brownian
      motion of single tethered DNA molecules. DNA containing two endonuclease
      recognition sites spaced a few 100 bp apart connect small polystyrene beads to a
      glass surface. The position of a bead is tracked through video microscopy.
      Protein-mediated looping and unlooping is then observed as a sudden specific
      change in Brownian motion of the bead. With this method we are able to directly
      follow DNA looping kinetics of single protein-DNA complexes to obtain loop
      stability and loop formation times. We show that, in the absence of divalent
      cations, NaeI induces DNA loops of specific size. In contrast, under these
      conditions NarI mainly creates non-specific loops, resulting in effective DNA
      compaction for higher enzyme concentrations. Addition of Ca2+ increases the NaeI
      DNA loop lifetime by two orders of magnitude and stimulates specific binding by
      NarI. Finally, for both enzymes we observe exponentially distributed loop
      formation times, indicating that looping is dominated by (re)binding the second
      recognition site.

PMID- 16407333
TI  - A novel multifunctional factor involved in trans-splicing of chloroplast introns
      in Chlamydomonas.
AB  - In the chloroplast of Chlamydomonas reinhardtii, psaA mRNA is spliced in trans
      from three separate precursors which assemble to form two group II introns. A
      fourth transcript, tscA, completes the structure of the first intron. Of the
      fourteen nucleus-encoded factors involved in psaA splicing, only two are required
      for splicing of both introns. We cloned and characterized the first of these more
      general factors, Raa1. Consistently with its role in psaA splicing, Raa1 is
      imported in the chloroplast where it is found in a membrane fraction and is part
      of a large ribonucleoprotein complex. One mutant, raa1-L137H, is defective for
      splicing of both introns, but another allelic mutant, raa1-314B, still expresses
      the 3' part of the Raa1 gene and is deficient only in splicing of intron 2. This
      observation and a deletion analysis indicate the presence of two domains in Raa1.
      The C-terminal domain is necessary and sufficient for processing of tscA RNA and
      splicing of the first intron, while the central domain is essential for splicing
      of the second intron. The combination of these two functional domains in Raa1
      suggests that this new factor may coordinate trans-splicing of the two introns to
      improve the efficiency of psaA maturation.

PMID- 16407334
TI  - The role of positively charged amino acids and electrostatic interactions in the
      complex of U1A protein and U1 hairpin II RNA.
AB  - Previous kinetic investigations of the N-terminal RNA recognition motif (RRM)
      domain of spliceosomal protein U1A, interacting with its RNA target U1 hairpin
      II, provided experimental evidence for a 'lure and lock' model of binding in
      which electrostatic interactions first guide the RNA to the protein, and close
      range interactions then lock the two molecules together. To further investigate
      the 'lure' step, here we examined the electrostatic roles of two sets of
      positively charged amino acids in U1A that do not make hydrogen bonds to the RNA:
      Lys20, Lys22 and Lys23 close to the RNA-binding site, and Arg7, Lys60 and Arg70,
      located on 'top' of the RRM domain, away from the RNA. Surface plasmon resonance
      based kinetic studies, supplemented with salt dependence experiments and
      molecular dynamics simulation, indicate that Lys20 predominantly plays a role in
      association, while nearby residues Lys22 and Lys23 appear to be at least as
      important for complex stability. In contrast, kinetic analyses of residues away
      from the RNA indicate that they have a minimal effect on association and
      stability. Thus, well-positioned positively charged residues can be important for
      both initial complex formation and complex maintenance, illustrating the multiple
      roles of electrostatic interactions in protein-RNA complexes.

PMID- 16407335
TI  - Hypoxic stress suppresses RNA polymerase III recruitment and tRNA gene
      transcription in cardiomyocytes.
AB  - RNA polymerase (pol) III transcription decreases when primary cultures of rat
      neonatal cardiomyocytes are exposed to low oxygen tension. Previous studies in
      fibroblasts have shown that the pol III-specific transcription factor IIIB
      (TFIIIB) is bound and regulated by the proto-oncogene product c-Myc, the mitogen
      activated protein kinase ERK and the retinoblastoma tumour suppressor protein,
      RB. The principal function of TFIIIB is to recruit pol III to its cognate gene
      template, an activity that is known to be inhibited by RB and stimulated by ERK.
      We demonstrate by chromatin immunoprecipitation (ChIP) that c-Myc also stimulates
      pol III recruitment by TFIIIB. However, hypoxic conditions cause TFIIIB
      dissociation from c-Myc and ERK, at the same time as increasing its interaction
      with RB. Consistent with this, ChIP assays indicate that the occupancy of tRNA
      genes by pol III is significantly reduced, whereas promoter binding by TFIIIB is
      undiminished. The data suggest that hypoxia can inhibit pol III transcription by
      altering the interactions between TFIIIB and its regulators and thus compromising
      its ability to recruit the polymerase. These effects are independent of cell
      cycle changes.

PMID- 16407336
TI  - Serine/arginine-rich splicing factors belong to a class of intrinsically
      disordered proteins.
AB  - Serine/arginine-rich (SR) splicing factors play an important role in constitutive
      and alternative splicing as well as during several steps of RNA metabolism.
      Despite the wealth of functional information about SR proteins accumulated to
      date, structural knowledge about the members of this family is very limited. To
      gain a better insight into structure-function relationships of SR proteins, we
      performed extensive sequence analysis of SR protein family members and combined
      it with ordered/disordered structure predictions. We found that SR proteins have
      properties characteristic of intrinsically disordered (ID) proteins. The amino
      acid composition and sequence complexity of SR proteins were very similar to
      those of the disordered protein regions. More detailed analysis showed that the
      SR proteins, and their RS domains in particular, are enriched in the disorder
      promoting residues and are depleted in the order-promoting residues as compared
      to the entire human proteome. Moreover, disorder predictions indicated that RS
      domains of SR proteins were completely unstructured. Two different classification
      methods, the charge-hydropathy measure and the cumulative distribution function
      (CDF) of the disorder scores, were in agreement with each other, and they both
      strongly predicted members of the SR protein family to be disordered. This study
      emphasizes the importance of the disordered structure for several functions of SR
      proteins, such as for spliceosome assembly and for interaction with multiple
      partners. In addition, it demonstrates the usefulness of order/disorder
      predictions for inferring protein structure from sequence.

PMID- 16407337
TI  - Enhancement and suppression of malaria in the Amazon.

PMID- 16407338
TI  - The effect of deforestation on the human-biting rate of Anopheles darlingi, the
      primary vector of Falciparum malaria in the Peruvian Amazon.
AB  - To examine the impact of tropical rain-forest destruction on malaria, we
      conducted a year-long study of the rates at which the primary malaria vector in
      the Amazon, Anopheles darlingi, fed on humans in areas with varying degrees of
      ecological alteration in the Peruvian Amazon. Mosquitoes were collected by human
      biting catches along the Iquitos-Nauta road at sites selected for type of
      vegetation and controlled for human presence. Deforested sites had an A. darlingi
      biting rate that was more than 278 times higher than the rate determined for
      areas that were predominantly forested. Our results indicate that A. darlingi
      displays significantly increased human-biting activity in areas that have
      undergone deforestation and development associated with road development.

PMID- 16407339
TI  - Four malaria success stories: how malaria burden was successfully reduced in
      Brazil, Eritrea, India, and Vietnam.
AB  - While many countries struggle to control malaria, four countries, Brazil,
      Eritrea, India, and Vietnam, have successfully reduced malaria burden. To
      determine what led these countries to achieve impact, published and unpublished
      reports were reviewed and selected program and partner staff were interviewed to
      identify common factors that contributed to these successes. Common success
      factors included conducive country conditions, a targeted technical approach
      using a package of effective tools, data-driven decision-making, active
      leadership at all levels of government, involvement of communities, decentralized
      implementation and control of finances, skilled technical and managerial capacity
      at national and sub-national levels, hands-on technical and programmatic support
      from partner agencies, and sufficient and flexible financing. All these factors
      were essential in achieving success. If the goals of Roll Back Malaria are to be
      achieved, governments and their partners must take the lessons learned from these
      program successes and apply them in other affected countries.

PMID- 16407340
TI  - Analysis of malaria cases in Bangladesh with remote sensing data.
AB  - Epidemiologic data of malaria cases were correlated with satellite-based
      vegetation health (VH) indices to investigate if they can be used as proxy for
      monitoring malaria epidemics in Bangladesh. The VH indices were represented by
      the vegetation condition index (VCI) and the temperature condition index (TCI).
      The VCI and TCI estimate moisture and thermal conditions, respectively.
      Sensitivity of VCI and TCI was assessed using correlation and regression
      analysis. During cooler months (November-March) when mosquitoes are less active,
      the correlation was low. It increased considerably during the warm and wet season
      (April-October), reaching 0.7 for the TCI in early October and -0.66 for the VCI
      in mid September.

PMID- 16407341
TI  - Successful treatment of Plasmodium falciparum malaria with a six-dose regimen of
      artemether-lumefantrine versus quinine-doxycycline in the Western Amazon region
      of Brazil.
AB  - This randomized, open-label study compared a three-day, six-dose regimen of
      artemether-lumefantrine with a five-day, 19-dose regimen of quinine-doxycycline
      for the treatment of Plasmodium falciparum malaria in the western Amazon region
      of Brazil. All patients remained hospitalized during their treatment and the
      study assessments were scheduled daily from the start of treatment (day 0)
      through day 6. By day 3, the percentage of infected patients was 0% in the
      artemether-lumefantrine group and 48.8% in the quinine-doxycycline group. Median
      parasite clearance time was significantly shorter in the artemether-lumefantrine
      group (two days) compared with the quinine-doxycycline group (three days) (P <
      0.0001). Two patients in the quinine-doxycycline group left the study early
      because of treatment ineffectiveness or adverse event. Adverse events were
      reported by 91.5% of the study participants, most of which were mild in severity
      and/or not considered related to study treatment. Artemether-lumefantrine was
      shown to be an efficacious, safe, and convenient treatment for P. falciparum
      malaria in a highly drug-resistant region of South America.

PMID- 16407342
TI  - Association of haptoglobin levels with age, parasite density, and haptoglobin
      genotype in a malaria-endemic area of Gabon.
AB  - Haptoglobin (Hp) levels were investigated in relation to host genotype in a
      malaria-endemic area in Gabon. A cross-sectional study of 1-12-year-old children
      was conducted in the rainy season, a period of high malaria transmission, to
      examine this relationship. Variables that influenced Hp levels were Hp genotype,
      location, and age interacting with parasite density. At low parasite densities,
      there was a negative correlation between Hp levels and age. At higher densities,
      there was a positive correlation with age. This suggests that in the presence of
      greater parasite-induced hemolysis, older children are capable of increased
      production of Hp. Sickle cell trait and ABO blood group was not associated with
      Hp levels in this population.

PMID- 16407343
TI  - Limited allelic diversity of Plasmodium falciparum merozoite surface protein 1
      gene from populations in the Solomon Islands.
AB  - Meiotic recombination generates allelic diversity in the Plasmodium falciparum
      merozoite surface protein 1 (msp1) gene. In this study, we monitored
      recombination-based diversity of msp1 in Guadalcanal, the Solomon Islands, where
      malaria transmission is high. We identified 5' recombinant types, 3' sequence
      types, and msp1 haplotypes (unique associations of 5' recombinant types and 3'
      sequence types), and compared them with those from areas of low transmission in
      Thailand and Vanuatu. The mean number of 5' recombinant types per person
      (multiplicity) was lower in Guadalcanal than in Thailand. Guadalcanal populations
      had 6-8 msp1 haplotypes; the numbers are comparable to Vanuatu but much lower
      than in Thailand. There were marked geographic differences in distribution of
      msp1 haplo-types. Linkage disequilibrium in msp1 was stronger in Guadalcanal than
      in Thailand, suggesting limited recombination events in the Solomon Islands. We
      suggest that the frequency of recombination events in msp1 is determined not only
      by transmission intensity but by the number of msp1 alleles prevalent and
      multiplicity of infections.

PMID- 16407344
TI  - CD4 T cell activation as a predictor for treatment failure in Ugandans with
      Plasmodium falciparum malaria.
AB  - Host immunity plays an important role in response to antimalarial therapy but is
      poorly understood. To test whether T cell activation is a risk factor for
      antimalarial treatment failure, we studied CD4(+) and CD8(+) T cell activation in
      31 human immunodeficiency virus-negative Ugandan patients 5-37 years of age who
      were treated for uncomplicated Plasmodium falciparum malaria. Increased CD4(+) T
      cell activation, as indicated by co-expression of HLA-DR and CD38, was an
      independent risk factor for treatment failure (hazard ratio = 2.45, 95%
      confidence interval = 1.02-5.89, P = 0.05) in multivariate analysis controlling
      for age, baseline temperature, and pre-treatment parasite density. The results
      provide insight into the role of cellular immunity in response to antimalarial
      therapy and underscore the need to investigate the mechanisms behind immune
      activation.

PMID- 16407346
TI  - Pupal habitat productivity of Anopheles gambiae complex mosquitoes in a rural
      village in western Kenya.
AB  - The productivity of larval habitats of the malaria vector Anopheles gambiae for
      pupae (the stage preceding adult metamorphosis) is poorly known, yet adult
      emergence from habitats is the primary determinant of vector density. To assess
      it, we used absolute sampling methods in four studies involving daily sampling
      for 25 days in 6 habitat types in a village in western Kenya. Anopheles gambiae
      s.s. comprised 82.5% of emergent adults and Anopheles arabiensis the remainder.
      Pupal production occurred from a subset of habitats, primarily soil burrow pits,
      and was discontinuous in time, even when larvae occupied all habitats
      continuously. Habitat stability was positively associated with pupal
      productivity. In a dry season, pupal productivity was distributed between burrow
      pits and pools in streambeds. Overall, these data support the notion that source
      reduction measures against recognizably productive habitats would be a useful
      component of an integrated management program for An. gambiae in villages.

PMID- 16407345
TI  - Distribution, description, and local knowledge of larval habitats of Anopheles
      gambiae s.l. in a village in western Kenya.
AB  - A sampling census revealed 104 aquatic habitats of 6 types for Anopheles gambiae
      s.l. larvae in a village in western Kenya, namely burrow pits, drainage channels,
      livestock hoof prints, rain pools, tire tracks, and pools in streambeds. Most
      habitats were created by human activity and were highly clustered in dispersion
      pattern within the village landscape. Landscape analysis revealed that six of
      forty-seven 0.09 km(2) cells superimposed over the village harbored 65% of all
      habitats. Focus group discussions and in-depth interviews with villagers revealed
      the extent of knowledge of the village residents of larval habitats, mosquito
      sources in the local environment, and what might be done to prevent mosquito
      breeding. Participants did not associate specific habitats with anopheline
      larvae, expressed reluctance to eliminate habitats because they were sources of
      domestic water supply, but indicated willingness to participate in a source
      reduction program if support were available.

PMID- 16407347
TI  - Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti
      to promote population replacement.
AB  - Control of arthropod-borne diseases based on population replacement with
      genetically modified non-competent vectors has been proposed as a promising
      alternative to conventional control strategies. Due to likely fitness costs
      associated with vectors manipulated to carry anti-pathogen effector genes, the
      effector genes will need to be coupled with a strong drive system to rapidly
      sweep them into natural populations. Endogenous meiotic drive systems have strong
      and stable population replacement potential, and have previously been reported in
      two mosquito species: Aedes aegypti and Culex pipiens. To investigate the
      influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics,
      we established three experimental population types that were initiated with 100%,
      10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and
      100% sensitive females (RED strain), respectively. Among the 100% and 10%
      populations, early generations were highly male biased, which reflected the
      effects of the meiotic driver, and remained more than 60% male by the F(15). A
      genetic marker tightly linked with the meiotic driver on chromosome 1 showed
      strong selection for the T37 strain-specific allele. Similar but reduced effects
      of the meiotic driver were also observed in the 1% populations. These results
      suggest that release of Ae. aegypti males carrying a strong meiotic driver into
      drive sensitive populations can be an effective tool for population replacement,
      and provide a foundation for additional studies including both experimental
      populations and simulations by mathematical modeling.

PMID- 16407348
TI  - Association between land cover and habitat productivity of malaria vectors in
      western Kenyan highlands.
AB  - We examined the effects of land cover type on survivorship and productivity of
      Anopheles gambiae in Kakamega in the western Kenyan highlands (elevation = 1,420
      1,580 meters above sea level). Under natural conditions, An. gambiae sensu lato
      adults emerged only from farmland habitats, with an estimated productivity of
      1.82 mosquitoes/meter(2)/week, but not from forest and swamp habitats. To
      determine the effects of intraspecific competition and land cover types, semi
      natural larval habitats were created within three land cover types (farmland,
      forest, and natural swamp), and three different densities of An. gambiae sensu
      stricto larvae were introduced to the larval habitats. The mosquito pupation rate
      in farmland habitats was significantly greater than in swamp and forest habitats,
      and larval-to-pupal development times were significantly shorter. At higher
      densities, the larvae responded to increased intraspecific competition by
      extending their development time and emerging as smaller adults, but initial
      larval density showed no significant effects on pupation rate. Land cover type
      may affect larval survivorship and adult productivity through its effects on
      water temperature and nutrients in the aquatic habitats, as shown by the
      significantly higher water temperature in farmland habitats, enhanced pupation
      rates and shortened development times from the addition of food to habitats, and
      a significant negative correlation of the occurrence of An. gambiae larvae with
      canopy cover and emergent plants in natural habitats. These results suggest that
      deforestation and cultivation of natural swamps in the western Kenyan highland
      create conditions favorable for the survival of An. gambiae larvae, and
      consequently increase the risks of malaria transmission to the human population.

PMID- 16407349
TI  - Evaluation of a new recombinant K39 rapid diagnostic test for Sudanese visceral
      leishmaniasis.
AB  - A new rK39 rapid diagnostic dipstick test (DiaMed-IT-Leish) was compared with
      aspiration and a direct agglutination test (DAT) for diagnosis of visceral
      leishmaniasis (VL) in 201 parasitologically confirmed cases, 133 endemic
      controls, and in 356 clinical suspects in disease-endemic and -epidemic areas in
      Sudan. The sensitivity of the rK39 test in parasitologically confirmed VL cases
      was 90%, whereas the specificity in disease-endemic controls was 99%. The
      sensitivity of the DAT was 98%. In clinically suspected cases, the sensitivity of
      the rK39 test was 81% and the specificity was 97%. When compared with the
      diagnostic protocol based on the DAT and aspiration used by Medecins sans
      Frontieres in epidemic situations, the positive predictive value was 98%, and the
      negative predictive value was 71%. This rK39 rapid diagnostic test is suitable
      for screening as well as diagnosis of VL. Further diagnostic work-up of dipstick
      negative patients with clinically suspected VL is important. The ease and
      convenience of the dipstick test will allow decentralization and improved access
      to care in disease-endemic areas in Sudan.

PMID- 16407350
TI  - Ecology of the leishmania species in the Guianan ecoregion complex.
AB  - In the Guianan ecoregion complex, at least seven Leishmania species belonging to
      both the L. (Leishmania) Saf' janova, 1982 and L. (Viannia) Lainson and Shaw,
      1987 sub-genera are causative agents of American visceral leishmaniasis,
      mucocutaneous leishmaniasis, and cutaneous leishmaniases, including localized and
      diffuse forms. They are mostly sylvatic species subjugated to their own specific
      Lutzomyia sand fly vectors and to particular wild mammalian reservoir hosts of
      the dense rain forest. Originally implicated strictly in wild zoonoses and
      developing in forested ecotopes, Leishmania show a particular adaptive plasticity
      to face environmental modifications following deforestation and anthropization.
      This review presents the different pathogenic complexes of these parasites,
      emphasizes their implication in human diseases, and considers the influence of
      humans on their ecology.

PMID- 16407351
TI  - Seroepidemiology of strongyloidiasis in the Peruvian Amazon.
AB  - A stool and serosurvey for Strongyloides stercoralis was conducted in a community
      in the Peruvian Amazon region. Strongyloidiasis stercoralis was identified in the
      stool of 69 (8.7%) of 792 participants. Six hundred nine sera were tested using
      by an enzyme-linked immunosorbent assay (ELISA), which had a sensitivity of 92%
      and a specificity of 94%; 442 (72%) were positive. In multivariable logistic
      regression models, having S. stercoralis in stool was associated with hookworm in
      the same specimen (odds ratio [OR] = 4.44, 95% confidence interval [CI] = 2.02
      9.79), occasionally or never wearing shoes (OR = 1.89, 95% CI = 1.10-3.27), and
      increasing age (OR = 1.012 for each one-year increase, 95% CI = 1.00-1.03).
      Similarly, occasionally or never wearing shoes (OR = 1.54, 95% CI = 1.01-2.37)
      and increasing age (OR = 1.04 for each one-year increase, 95% CI = 1.02-1.06)
      were associated with an increased risk of a positive S. stercoralis ELISA result.
      The ELISA had a negative predictive value of 98% and is an excellent screening
      test for strongyloidiasis.

PMID- 16407352
TI  - Ultrasound and clinical investigation of hepatosplenic schistosomiasis:
      evaluation of splenomegaly and liver fibrosis four years after mass chemotherapy
      with oxamniquine.
AB  - The course of hepatosplenic schistosomiasis after mass chemotherapy with
      oxamniquine has been rarely reported. We report the effect of treatment in
      patients with advanced schistosomiasis mansoni living in area of Brazil highly
      endemic for this disease. A total of 739 inhabitants of a village were subjected
      to clinical and abdominal ultrasound examinations and were treated with
      oxamniquine. We have identified 84 individuals with hepatosplenic
      schistosomiasis. Alcohol abuse was associated with periportal thickening. Four
      years after treatment, 42 of the 84 individuals were re-examined and regression
      of splenomegaly was observed in 59% and of periportal thickening in 32%. Our data
      indicate that mass chemotherapy can lead to reduction of schistosomiasis
      morbidity but a significant group of patients (68%) will not improve. The
      association with alcohol abuse should be further evaluated. Thickening of the
      gallbladder wall can be a useful predictor of no involution of liver fibrosis
      after treatment.

PMID- 16407353
TI  - Causes of fever in adults on the Thai-Myanmar border.
AB  - A hospital-based study was conducted along the Thai-Myanmar border to provide
      greater knowledge of the causes of febrile illness and to determine what zoonotic
      and vector-borne emerging infectious diseases might be present. A total of 613
      adults were enrolled from June 1999 to March 2002. Cases were classified based on
      clinical findings and laboratory results. An etiologic diagnosis was made for 48%
      of subjects. Malaria was the most common diagnosis, accounting for 25% of
      subjects, with two-thirds Plasmodium falciparum. Serologic evidence for
      leptospirosis was found in 17% of subjects. Other etiologic diagnoses included
      rickettsial infections, dengue fever, and typhoid. The most frequent clinical
      diagnoses were nonspecific febrile illness, respiratory infections, and
      gastroenteritis. Clinical associations were generally not predictive of etiologic
      diagnosis. Apparent dual diagnoses were common, particularly for malaria and
      leptospirosis. Findings have been used to modify treatment of unspecified febrile
      illness in the area.

PMID- 16407355
TI  - First detection of Rickettsia felis in Ctenocephalides felis fleas parasitizing
      rats in Cyprus.
AB  - Rickettsia felis was identified by polymerase chain reaction amplification and
      DNA sequencing analysis in Ctenocephalides felis fleas parasitizing rats in
      Cyprus. Murine typhus caused by R. typhi was believed to be the only flea
      transmitted rickettsiosis on the island. This is the first report of this
      pathogen in southeastern Europe.

PMID- 16407354
TI  - Population-based surveillance of typhoid fever in Egypt.
AB  - Credible measures of disease incidence are necessary to guide typhoid fever
      control efforts. In Egypt, incidence estimates have been derived from hospital
      based syndromic surveillance, which may not represent the population with typhoid
      fever. To determine the population-based incidence of typhoid fever in Fayoum
      Governorate (pop. 2,240,000), we established laboratory-based surveillance at
      five tiers of health care. Incidence estimates were adjusted for sampling and
      test sensitivity. Of 1,815 patients evaluated, cultures yielded 90 (5%)
      Salmonella Typhi isolates. The estimated incidence of typhoid fever was
      59/100,000 persons/year. We estimate 71% of typhoid fever patients are managed by
      primary care providers. Multidrug-resistant (MDR) Salmonella Typhi (resistant to
      chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) was isolated from
      26 (29%) patients. Population-based surveillance indicates moderate typhoid fever
      incidence in Fayoum, and a concerning prevalence of MDR typhoid. The majority of
      patients are evaluated at the primary care level and would not have been detected
      by hospital-based surveillance.

PMID- 16407356
TI  - Serological evidence of infection with Rickettsia typhi and Rickettsia felis
      among the human population of Catalonia, in the northeast of Spain.
AB  - Murine typhus (MT) is a cause of fever of intermediate duration in the south of
      Spain. Rickettsia typhi has been described as the MT etiological agent.
      Rickettsia felis produces an infection similar to MT. The aim of the study is to
      determine their seroprevalence in humans in Catalonia. Antibodies to Rickettsia
      typhi and Rickettsia felis from 217 serum samples were examined by indirect
      immunofluorescence assay (IFA). Age, gender, residence area, contact with
      animals, and occupation were surveyed. Rickettsia typhi and Rickettsia felis
      seroprevalences were 8.8% and 3.2%, respectively. Rickettsia typhi was present in
      7.6% of the samples in urban, 8.5% in semirural, and in 21.4% in rural areas,
      whereas Rickettsia felis was present in 3.5% in urban, 1.7% in semirural, and
      7.1% in rural area. The only statistically significant association observed was
      that between Rickettsia felis seropositivity and age. Our data seem to indicate
      the presence of Rickettsia typhi and Rickettsia felis in humans in Catalonia.

PMID- 16407357
TI  - An outbreak of leptospirosis among Israeli troops near the Jordan River.
AB  - An outbreak of leptospirosis that involved 7 of a team of 27 Israeli troops
      occurred following a military exercise in northern Israel near the Jordan River.
      The organism implicated in the outbreak was Leptospira interrogans serovar
      Hardjo. The clinical course was uncomplicated and all patients fully recovered.
      There were no cases of asymptomatic infection. Military personnel should be
      recognized as having an occupational risk for contracting leptospirosis,
      especially when military activity takes place near natural water sources
      inhabited by cattle, taking into account the local epidemiology of this disease.
      Moreover, outbreaks among military personnel may serve as a sentinel for
      leptospiral illness in areas in which civilian exposure takes place, such as the
      Jordan River, which is an important site that involves immersion in the context
      of both pilgrimage and civilian recreational activities."Bathe and you will
      become clean. So he went down and immersed himself seven times in the Jordan, as
      Elisha had told him to do. And his flesh became clean once more like the flesh of
      a small child."II Kings 5:14.

PMID- 16407358
TI  - Quantitative analysis of dengue-2 virus RNA during the extrinsic incubation
      period in individual Aedes aegypti.
AB  - Dengue virus-2 (DENV-2) RNA was quantified from the midgut and legs of individual
      Aedes aegypti at each of 14 days postinfectious blood meal (dpi) in a DENV-2
      susceptible strain from Chetumal, Mexico. A SYBR Green I based strand-specific,
      quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR)
      assay was developed. The lower detection and quantitation limits were 20 and 200
      copies per reaction, respectively. Amounts of positive and negative strand viral
      RNA strands were correlated. Numbers of plaque-forming units (PFU) were
      correlated with DENV-2 RNA copy number in both C6/36 cell cultures and
      mosquitoes. PFU were consistently lower than RNA copy number by 2-3 log(10).
      Midgut levels of DENV-2 RNA peaked 8 dpi and fluctuated erratically between 6 and
      9 dpi. Copies of DENV-2 RNA varied significantly among infected mosquitoes at
      each time point. Quantitative real-time RT-PCR is a convenient and reliable
      method that provides new insights into virus-vector interactions.

PMID- 16407360
TI  - Clinic-based surveillance for bacterial- and rotavirus-associated diarrhea in
      Egyptian children.
AB  - To identify enteropathogens for vaccine development, we implemented clinic-based
      surveillance for severe pediatric diarrhea in Egypt's Nile River Delta. Over 2
      years, a physician clinically evaluated and obtained stool samples for
      microbiology from patients with diarrhea and less than 6 years of age. In the
      first (N = 714) and second clinic (N = 561), respectively, 36% (N = 254) and 46%
      (N = 260) of children were infected with rotavirus, enterotoxigenic Escherichia
      coli (ETEC), Campylobacter, or Shigella. When excluding mixed rotavirus-bacterial
      infections, for the first and second clinic, 23% and 10% had rotavirus-associated
      diarrhea, and 14% and 17% had ETEC-associated diarrhea, respectively.
      Campylobacter-associated diarrhea was 1% and 3%, and Shigella-associated diarrhea
      was 2% and 1%, respectively, for the two clinics. Rotavirus-associated diarrhea
      peaked in late summer to early winter, while bacterial agents were prevalent
      during summer. Rotavirus-associated cases presented with dehydration, vomiting,
      and were often hospitalized. Children with Shigella- or Campylobacter-associated
      diarrhea reported as watery diarrhea and rarely dysentery. ETEC did not have any
      clinically distinct characteristics. For vaccine development and/or deployment,
      our study suggests that rotavirus is of principle concern, followed by ETEC,
      Shigella, and Campylobacter.

PMID- 16407359
TI  - Correlation of serum levels of macrophage migration inhibitory factor with
      disease severity and clinical outcome in dengue patients.
AB  - Dengue virus infection can cause mild dengue fever (DF) or severe dengue
      hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Cytokines are believed
      to be involved in the pathogenesis of dengue infection. However, the role of the
      pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in dengue
      infection is unclear. In this study, serum levels of MIF in adult dengue patients
      with different disease severity and clinical outcome were determined and compared
      with the levels of other cytokines, tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), IL-10, and interferon gamma (IFN-gamma), in the same
      patients. Serum levels of MIF, IL-6, and IL-10, but not IFN-gamma or TNF-alpha,
      were higher in all DHF patients who died than in DHF survivors and DF patients.
      We conclude that in addition to IL-6 and IL-10, elevated levels of serum MIF are
      a potential predictor of disease severity and clinical outcome in dengue
      patients.

PMID- 16407361
TI  - Delayed-type hypersensitivity skin test reactivity and survival in HIV-infected
      patients in Uganda: should anergy be a criterion to start antiretroviral therapy
      in low-income countries?
AB  - Access to antiretroviral (ARV) drugs is improving in sub-Saharan Africa but still
      constrained by several clinical and logistical obstacles. There is a need to
      develop affordable markers to guide initiation of treatment. We present a
      prospective cohort study of 779 patients participating in a TB prophylaxis trial.
      We performed separate analyses for anergic and nonanergic subjects. Prognostic
      factors for anergic and nonanergic subjects differed between groups. Individuals
      with anergy and constitutional symptoms were at the highest risk of death.
      Incident tuberculosis and CD4 < 200 cells/muL at enrollment were the strongest
      risk factors for death. HIV disease is associated with substantial morbidity and
      mortality in this population. The burden caused by tuberculosis is particularly
      high. Anergy is a strong and independent predictor of death. World Health
      Organization criteria to start ARV may be strengthened with the addition of DTH
      testing, an inexpensive and readily available tool in sub-Saharan Africa.

PMID- 16407363
TI  - Respiratory syncytial virus infections in northeastern Brazil: seasonal trends
      and general aspects.
AB  - Respiratory syncytial virus (RSV) is one of the most prevalent agents of acute
      respiratory infections in children. Consistent data about seasonality of
      infections caused by this virus in Brazil proceed only from southern and
      southeastern regions. The purpose of this study was to determine the prevalence
      and the seasonal pattern of RSV infections in children living in Fortaleza city
      in northeastern Brazil. Nasopharyngeal aspirates of 1,950 patients attending in
      ambulatories, emergency room, and wards of Hospital Infantil Albert Sabin were
      collected and screened for RSV infections during 43 consecutive months. RSV was
      detected in 21% of the cases. RSV seasons in Fortaleza lasted 6 to 8 consecutive
      months, starting in January or February and finishing in July or August, and were
      associated with the rainy season.

PMID- 16407362
TI  - Prevalence of intestinal parasites including microsporidia in human
      immunodeficiency virus-infected adults in Cameroon: a cross-sectional study.
AB  - To assess the prevalence of intestinal parasites in a cohort of human
      immunodeficiency virus (HIV)-infected adults in Cameroon, a cross-sectional study
      was conducted. Detection of parasites was performed in 181 stool samples from 154
      HIV-infected patients with a mean CD4 cell count of 238 cells/mm(3). Only 35
      patients (22%) were receiving antiretroviral therapy at the time of stool
      sampling, and 46 (29%) had diarrhea. Opportunistic protozoa were found in 15
      patients (9.7%), 8 of whom (53%) had diarrhea. Enterocytozoon bieneusi was found
      in eight patients, C. parvum in six patients, and Isospora belli in three
      patients. All E. bieneusi isolates tested belonged to the same genotype. The
      prevalence of opportunistic protozoa among patients with CD4 cell counts less
      than 50/mm(3) was 32%.

PMID- 16407364
TI  - Modeling the impact of variable climatic factors on the crossover of Culex
      restauns and Culex pipiens (Diptera: culicidae), vectors of West Nile virus in
      Illinois.
AB  - The aim of this study was to model the impact of temperature on the timing of the
      seasonal shift in relative proportion of Culex restuans Theobald and Culex
      pipiens L. in Illinois. The temporal pattern of West Nile virus (WNV) and St.
      Louis encephalitis virus transmission in the midwest exhibits a late summer to
      early fall peak in activity, which parallels the temporal increase in the
      abundance of Cx. pipiens. The daily number of egg rafts oviposited by each
      species has been monitored at multiple surveillance sites in Urbana-Champaign in
      central Illinois for more than 13 years. The time when the two Culex species are
      in equal abundance (crossover) varies considerably from year to year. Our
      investigation of several thermal measures indicated that this variation was
      related in large part to climatic conditions with warmer (cooler) temperatures
      correlated to earlier (later) crossover dates. Models based on degree days and
      the number of days in which the daily maximum temperature exceeded an upper
      temperature threshold explained more than 60% of the variance in crossover dates.
      In contrast, models based on the number of days in which the daily minimum
      temperature exceeded a lower temperature threshold explained no more than 52% of
      the variance. An evaluation of these models demonstrated that they provide
      relatively simple and accurate estimates of crossover date from daily temperature
      data, a necessary component for developing an overall climatic index for the risk
      of WNV transmission in Illinois.

PMID- 16407365
TI  - Changes in seroprevalence of West Nile virus across Illinois in free-ranging
      birds from 2001 through 2004.
AB  - Of the 5,236 birds sampled for antibodies to West Nile virus (WNV) in Illinois
      from 2001 through 2004, 348 (6.6%) birds were seropositive. Our multiple year
      surveillance identified several avian species that had particularly high
      percentages of seropositive individuals. The importance of these species in the
      enzootic and/or epizootic transmission of WNV is discussed relative to their
      regional abundance and literature on host competency. The species with the
      highest exposure rates to WNV differed both temporally and regionally. In
      general, birds that bred or were born in Illinois were more likely to have
      antibodies than transient birds. There was also a significant difference in the
      seroprevalence between adults (12.1%) and juveniles (5.5%), indicating that the
      acquired antibody response from previous years is a critical concern when
      interpreting seroprevalence rates in wild-caught birds. The most common hosts for
      St. Louis encephalitis virus were also the most common hosts for WNV, which
      strongly supports the role of similar vectors for both flaviviruses. Avian
      species with high WNV seroprevalence rates tended to be those that bred
      throughout the year, have open cup nests, and live in close proximity to humans.

PMID- 16407369
TI  - Mitochondrial DNA mutations in oral squamous cell carcinoma.
AB  - It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations
      within the ND2 gene of histologically normal parotid salivary gland tissue of
      smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral
      squamous cell carcinoma (SCC) is strongly related to cigarette smoking;
      therefore, we used PCR and direct sequencing to establish whether mtDNA mutations
      were also present in oral SCC which could be used as additional biomarkers for
      smoking-associated DNA damage. In addition to searching for mutations in the ND2
      gene, the mitochondrial D-Loop was also analysed. Three mutation hotspots were
      observed in the D-Loop at nt 146, 152 and 186, two of which (nt 146 and 152) have
      also been implicated in oesophageal SCC, another smoking-related cancer. The
      mutation hotspot observed at nt 186 has not previously been reported in other
      tumours. Furthermore, we show that the mutations previously reported within the
      ND2 gene in normal parotid tissue of smokers were not evident in these samples,
      but that a mutation hotspot occurs at nucleotide 4917 in oral SCC. We also show
      that D-Loop mutations occur predominantly in male smokers and female non-smokers
      and that this association with gender is statistically significant (P = 0.003).
      We conclude that the mtDNA mutation hotspots found in this study, in particular
      nt 186, are potential biomarkers for oral SCC. However, owing to gender-specific
      differences in occurrence in smokers and non-smokers, and a lack of environmental
      smoking history, in general, it is difficult to associate these mutations with
      mtDNA damage induced by smoking. If the mutations observed in the subset of male
      patients are smoking induced, given our previous findings, mutation hotspots in
      the ND2 gene may be tissue specific suggesting the causative mutagens for mtDNA
      damage within these tissues are likely to be different.

PMID- 16407368
TI  - IL-10 deficiency leads to somatic mutations in a model of IBD.
AB  - Individuals with inflammatory bowel disease (IBD) are at increased risk of
      developing gastrointestinal cancer. Here, we have tested the possibility that
      chronic inflammation could trigger mutations. For this, we have used IL-10
      deficient (IL-10-/-) mice, which spontaneously develop intestinal inflammation,
      in combination with a transgenic gpt gene and red/gam gene (gpt+IL-10-/-), which
      is a well-characterized mutation reporter locus. The total mutation frequency in
      the colon of gpt+IL-10-/- mice was about five times higher than that in normal
      gpt+IL-10+/+ mice. In the particular case of G:C to A:T transitions, the
      frequency of mutations in gpt+IL-10-/- mice was 4.1 times higher than that in
      control mice. Interestingly, the frequency of small deletions and insertions was
      also strikingly increased (approximately 10 times). The majority of the deletion
      or insertion mutations were observed in the monotonous base runs or adjacent
      repeats of short tandem sequences. In contrast, the frequency of large deletions,
      detected by loss of the Spi marker present in the red/gam transgene, was similar
      among the mouse strains. Finally, as a control, the mutation frequency in non
      inflamed tissues, such as the liver, were similar between gpt+IL-10-/- mice and
      gpt+IL-10+/+ mice. Our data demonstrate that the chronic inflammatory environment
      in the colon promotes the generation of mutations.

PMID- 16407370
TI  - Histone acetylation dependent allelic expression imbalance of BAPX1 in patients
      with the oculo-auriculo-vertebral spectrum.
AB  - The oculo-auriculo-vertebral spectrum (OAVS) (OMIM % 164210) is a common
      developmental disorder characterized by hemifacial microsomia, epibulbar tumours,
      ear malformation and vertebral anomalies. Although rare familial cases suggest
      that OAVS has a genetic basis, no genetic defect has been identified so far. In a
      patient with OAVS and a chromosomal translocation t(4;8) we have found that the
      chromosome 4 breakpoint is 76.4 kb distal to the BAPX1 gene, which plays an
      essential role in craniofacial development. We did not detect any BAPX1 mutation
      in 105 patients, but observed a strong allelic expression imbalance (sAEI) in
      fibroblasts from five of 12 patients, but not in nine normal controls (Fisher's
      exact test, P=0.038). sAEI was de novo in one patient and inherited in two other
      patients. Prolonged cell culture or treatment with the histone deacetylase
      inhibitor Trichostatin A led to reactivation of the downregulated allele. We
      propose that epigenetic dysregulation of BAPX1 plays an important role in OAVS.

PMID- 16407371
TI  - Proteolytic cleavage of polyglutamine-expanded ataxin-3 is critical for
      aggregation and sequestration of non-expanded ataxin-3.
AB  - Spinocerebellar ataxia type 3 (SCA3), like other polyglutamine (polyQ) diseases,
      is characterized by the formation of intraneuronal inclusions, but the mechanism
      underlying their formation is poorly understood. Here, we tested the "toxic
      fragment hypothesis", which predicts that proteolytic production of polyQ
      containing fragments from the full-length disease protein initiates the
      aggregation process associated with inclusion formation and cellular dysfunction.
      We demonstrate that the removal of the N-terminus of polyQ-expanded ataxin-3
      (AT3) is required for aggregation in vitro and in vivo. Consistently, proteolytic
      cleavage of full-length, pathogenic AT3 initiates the formation of sodium
      dodecylsulfate-resistant aggregates in neuroblastoma cells. Although full-length
      AT3 does not readily aggregate on its own, it is susceptible to co-aggregation
      with polyQ-expanded AT3 fragments. Interestingly, interaction with soluble polyQ
      elongated fragments causes a structural distortion of wild-type AT3 prior to the
      formation of stable co-aggregates. These results establish the critical role of C
      terminal, proteolytic fragments of AT3 in the molecular pathomechanism of SCA3,
      in strong support of the toxic fragment hypothesis.

PMID- 16407372
TI  - Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.
AB  - A family history of disease is a strong risk factor for testicular germ cell
      tumour (TGCT). In order to identify the location of putative TGCT susceptibility
      gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of
      TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an
      average inter-marker distance of 10 cM. An additional 58 pedigrees were used to
      more intensively investigate several genomic regions of interest. Genetic linkage
      analysis was performed with the ALLEGRO software using two model-based parametric
      analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23,
      3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores
      of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation
      studies indicate that the observed number of HLOD peaks greater than one does not
      differ significantly from that expected by chance. A TGCT locus at Xq27 has been
      previously reported. Of the 237 pedigrees examined in this study, 66 were
      previously unstudied at Xq27, no evidence for linkage to this region was observed
      in this new pedigree set. Overall, the results indicate that no single major
      locus can account for the majority of the familial aggregation of TGCT, and
      suggests that multiple susceptibility loci with weak effects contribute to the
      disease.

PMID- 16407373
TI  - Forecasting mortality: dynamic assessment of risk in ST-segment elevation acute
      myocardial infarction.
AB  - AIMS: To demonstrate the feasibility and clinical utility of developing dynamic
      risk assessment models for ST-segment elevation myocardial infarction (STEMI)
      patients. METHODS AND RESULTS: In 6066 STEMI patients enrolled in the Assessment
      of the Safety and Efficacy of a New Thrombolytic-3 (ASSENT-3) trial with complete
      electrocardiographic data, we assessed the probability of 30-day mortality over
      the following forecasting periods beginning at day 0 (baseline), 3 h, day 2, and
      day 5 using multiple-logistic regression. These models were validated and
      simplified in independent samples of 1622 similar fibrinolytic-treated patients
      from the ASSENT-3 PLUS trial and in 814 STEMI patients undergoing primary
      percutaneous coronary intervention in the COMplement inhibition in Myocardial
      infarction treated with Angioplasty (COMMA) trial. The discriminatory power of
      these predictive models, from baseline to day 5, was excellent (c-statistics 0.80
      to 0.87); and their predictive ability was supported by strong gradients in
      mortality outcomes as the risk score increased. Dynamic modelling also provided
      information on the change in prognosis over time which may be used to advise more
      appropriate therapeutic decisions, e.g. the identification of high-risk patients
      for possible co-interventions. CONCLUSION: Dynamic modelling for STEMI patients
      enhances the risk assessment and stratification and should provide valuable
      ongoing guidance for their management.

PMID- 16407374
TI  - Moderate renal insufficiency at 70 years predicts mortality.
AB  - BACKGROUND: Glomerular filtration rate (GFR) diminishes with age. Kidney function
      in the elderly is often assessed by serum creatinine alone, although it is
      insensitive in this age group. Formulae for predicting GFR are not widely used.
      AIM: To study the effect of low predicted GFR on mortality. DESIGN: Longitudinal
      cohort study. SETTING: The community-based Jerusalem Seventy Year Olds
      Longitudinal Study. METHODS: We studied 445 subjects, all aged 70 years, using
      questionnaires, a medical examination with history-taking, and standard
      laboratory tests. Moderate renal insufficiency was defined as a predicted GFR of
      <60 ml/min, based on the Cockcroft-Gault (CG) and the Modification of Diet in
      Renal Disease (MDRD) equations. RESULTS: Predicted GFR was normally distributed,
      with a mean +/- SD of 62.4 +/- 15.27 ml/min. Predicted GFR was <60 ml/min in 221
      (46%), most of whom had normal serum creatinine. Twelve-year mortality was 38.7%
      in these 221 vs. 27% in the other 204. The survival advantage was already evident
      after 3 years. Under Cox proportional hazard analysis using numerous common risk
      factors as independent variables, lower predicted GFR had a significant mortality
      risk (hazard ratio 2.108, 95%CI 1.43-3.12, p = 0.0002). DISCUSSION: In community
      dwelling elderly people, moderate renal insufficiency as assessed using the CG
      equation is a strong and independent predictor of mortality. Most of these at
      risk patients have 'normal' serum creatinine.

PMID- 16407375
TI  - Cancer risks in LKB1 germline mutation carriers.
AB  - BACKGROUND AND AIMS: Germline mutations in the LKB1 gene are known to cause Peutz
      Jeghers syndrome, which is an autosomal dominant disorder characterised by
      hamartomatous polyposis and mucocutaneous pigmentation. This syndrome is
      associated with an increased risk of malignancies in different organs but there
      is a lack of data on cancer range and risk in LKB1 germline mutation carriers.
      PATIENTS AND METHODS: The cumulative incidence of cancer in 149 Peutz-Jeghers
      syndrome patients with germline mutation(s) in LKB1 was estimated using Kaplan
      Meier time to cancer onset analyses and compared between relevant subgroups with
      log rank tests. RESULTS: Thirty two cancers were found in LKB1 mutation carriers.
      Overall cancer risks at ages 30, 40, 50, 60, and 70 years were 6%, 18%, 31%, 41%,
      and 67%, respectively. There were similar overall cancer risks between male and
      female carriers. However, there were overall cancer risk differences for exon 6
      mutation carriers versus non-exon 6 mutation carriers (log rank p=0.022 overall,
      0.56 in males, 0.0000084 in females). Most (22/32) of the cancers occurred in the
      gastrointestinal tract, and the overall gastrointestinal cancer risks at ages 40,
      50, 60, and 70 years were 12%, 24%, 34%, and 63%, respectively. In females, the
      risks for developing gynaecologic cancer at ages 40 and 50 years were 13% and
      18%, respectively. CONCLUSIONS: Mutations in exon 6 of LKB1 are associated with a
      higher cancer risk than mutations within other regions of the gene. Moreover,
      this study provides age related cumulative risks of developing cancer in LKB1
      mutation carriers that should be useful for developing a tailor made cancer
      surveillance protocol for Peutz-Jeghers syndrome patients.

PMID- 16407377
TI  - A molecular revolution in the study of intestinal microflora.
AB  - Bacterial colonisers of the colon comprise several hundred bacterial species that
      live in a complex ecosystem. Study of this complex ecosystem has been carried
      out, until recently, by traditional culture techniques with biochemical methods
      to identify organisms. The development of molecular techniques to investigate
      ecological microbial communities has provided the microbiologist with a vast
      array of new techniques to investigate human intestinal microflora. Metagenomics,
      the science of biological diversity, combines the use of molecular biology and
      genetics to identify and characterise genetic material from complex microbial
      environments. The combination of metagenomics and subsequent quantitation of each
      identified species using molecular techniques allows the relatively rapid
      analysis of whole bacterial populations in human health and disease.

PMID- 16407376
TI  - CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised
      by quantitative DNA methylation analysis and prospective cohort studies.
AB  - BACKGROUND: The concept of CpG island methylator phenotype (CIMP) is not
      universally accepted. Even if specific clinicopathological features have been
      associated with CIMP, investigators often failed to demonstrate a bimodal
      distribution of the number of methylated markers, which would suggest CIMP as a
      distinct subtype of colorectal cancer. Previous studies primarily used
      methylation specific polymerase chain reaction which might detect biologically
      insignificant low levels of methylation. AIM: To demonstrate a distinct genetic
      profile of CIMP colorectal cancer using quantitative DNA methylation analysis
      that can distinguish high from low levels of DNA methylation. MATERIALS AND
      METHODS: We developed quantitative real time polymerase chain reaction
      (MethyLight) assays and measured DNA methylation (percentage of methylated
      reference) of five carefully selected loci (promoters of CACNA1G, CDKN2A (p16),
      CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective
      cohorts. RESULTS: There was a clear bimodal distribution of 80 microsatellite
      instability-high (MSI-H) tumours according to the number of methylated promoters,
      with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having
      >or=4/5 methylated loci, and 17% (78) of the 460 tumours were classified as CIMP.
      CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild
      type KRAS. Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours
      showed much higher frequencies of BRAF mutations (63% and 54%) than non-CIMP
      counterparts (non-CIMP MSI-H (0%, p<10(-5)) and non-CIMP MSS tumours (6.6%, p<10(
      4)), respectively). CONCLUSION: CIMP is best characterised by quantitative DNA
      methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may
      be less frequent than previously reported.

PMID- 16407378
TI  - Mechanisms of increased acid secretion after eradication of Helicobacter pylori
      infection.
AB  - Eradication of Helicobacter pylori infection leads to recovery of gastric acid
      secretion in some individuals but the mechanism is not fully understood. In the
      short term, there is an impressive increase in expression of H+/K+-ATPase pumps
      without an increase in the number of parietal cells. Longer follow up studies are
      needed to see if the parietal cell mass eventually recovers.

PMID- 16407379
TI  - Can modulating corticotropin releasing hormone receptors alter visceral
      sensitivity?
AB  - Activation of corticotropin releasing hormone (CRH) receptor 2 (CRH-R2) reduces
      visceral sensitivity induced by colorectal distension in conscious rats. This
      finding is relevant to the increased interest in the potential use of therapeutic
      agents that act on CRH receptors in the treatment of irritable bowel syndrome.

PMID- 16407380
TI  - To be or not to be--an incretin or enterogastrone?
AB  - Glucagon-like peptide 1 does not comfortably fulfil the criterion of a gut
      derived factor responsible for an enhanced meal related insulin response; it
      appears logical to add the definition of a "physiological incretin hormone".

PMID- 16407381
TI  - Anticipating disaster: the genetics of familial pancreatic cancer.
AB  - To be born into a family with familial pancreatic cancer, an inheritable,
      autosomal dominant disorder, has various implications for an individual's life-
      and none is fortunate. The prospects just turned even darker because of
      "anticipation", the phenomenon that successive generations are affected by an
      inheritable disorder at a progressively earlier age. An up to date study shows
      that "anticipation" is also operative in familial pancreatic cancer, meaning that
      affected children die approximately 10 years earlier than their affected parents.

PMID- 16407382
TI  - An unusual cause of pancreatitis--patient with dominant dorsal pancreatic duct
      syndrome and intraductal papillary mucinous neoplasm (IPMN) in the ventral
      pancreatic duct.

PMID- 16407383
TI  - Silent disease revealed by a fruit--ileal obstruction.

PMID- 16407384
TI  - Capsule endoscopy in the management of a patient with a rare syndrome--yellow
      nail syndrome with intestinal lymphangiectasia.

PMID- 16407385
TI  - Micellar solubilisation of cholesterol is essential for absorption in humans.
AB  - BACKGROUND AND AIMS: Intralumenal bile acid (BA) concentrations have a profound
      effect on cholesterol absorption. We performed studies to assess the effects of
      markedly reduced lumenal BA on cholesterol absorption in children with inborn
      errors in BA synthesis and the role of micellar solubilisation of cholesterol on
      its absorption in an animal model using human intestinal contents. METHODS: We
      studied five subjects: two with 3beta hydroxy-C27 steroid dehydrogenase isomerase
      deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5beta reductase deficiency
      (5beta reductase), and one with 2-methylacyl CoA racemase deficiency (racemase).
      Subjects were studied on supplemental BA therapy and three weeks after withdrawal
      of supplements. During each treatment period a liquid meal was consumed. Duodenal
      samples were collected and analysed, and cholesterol absorption and cholesterol
      fractional synthetic rates were measured. Human intralumenal contents were
      infused in a bile diverted rat lymph fistula model to assess micellar versus
      vesicular absorption of cholesterol. RESULTS: Without BA supplementation,
      intralumenal BA concentrations were below the critical micellar concentration
      (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA
      supplementation. Lumenal cholesterol was carried primarily as vesicles in
      untreated subjects whereas it was carried as both micelles and vesicles in
      treated subjects. Cholesterol absorption increased approximately 55% in treated
      compared with untreated subjects (p=0.041), with a simultaneous 70% decrease in
      synthesis rates (p=0.029). In the rat lymph fistula model, minimal vesicular
      cholesterol was absorbed whereas vesicular and micellar fatty acid and
      phospholipid were comparably absorbed. CONCLUSIONS: Increasing micellar
      cholesterol solubilisation by supplemental BA in subjects with inborn errors of
      BA synthesis leads to an improvement in cholesterol absorption and reduction in
      cholesterol synthesis due to improved micellar solubilisation of cholesterol.

PMID- 16407386
TI  - Blurred vision: cause? Retinopathy secondary to interferon treatment.

PMID- 16407388
TI  - Intractable diarrhoea of infancy caused by neutrophil specific granule deficiency
      and cured by stem cell transplantation.

PMID- 16407389
TI  - Bilateral thoracoscopic splanchnicectomy in chronic intestinal pseudo
      obstruction: report of two paediatric cases.

PMID- 16407390
TI  - Secondary amyloidosis in Crohn's disease: treatment with tumour necrosis factor
      inhibitor.

PMID- 16407387
TI  - Layers of mutualism with commensal bacteria protect us from intestinal
      inflammation.

PMID- 16407391
TI  - The stomach periglandular fibroblast sheath: all present and correct.

PMID- 16407392
TI  - Anti-saccharomyces cerevisiae antibodies (ASCA) in coeliac disease.

PMID- 16407393
TI  - The non-host pathogen Botrytis cinerea enhances glucose transport in Pinus
      pinaster suspension-cultured cells.
AB  - Botrytis cinerea is the causal agent of grey mould disease and a non-host
      necrotrophic pathogen of maritime pine (Pinus pinaster). Recent evidence suggests
      that pathogen challenge can alter carbon uptake in plant cells; however, little
      is known on how elicitor-derived signalling pathways control sugar transport
      activity. P. pinaster suspended cells are able to absorb D-[14C]glucose with high
      affinity, have an H+-dependent transport system (Km, 0.07 mM; Vmax, 1.5 nmol min(
      1) mg(-1) DW), are specific for D-glucose, D-fructose, D-galactose and D-xylose,
      and are subject to glucose repression. When elicited by B. cinera spores,
      suspended cells exhibit calcium-dependent biphasic reactive oxygen species (ROS)
      production, the second burst also being dependent on NADPH oxidase, mitogen
      activated protein kinase (MAPK), and de novo transcription and protein synthesis.
      Challenging suspended cells incubated in sugar-free medium resulted in an up to 3
      fold increase in glucose transport capacity over non-elicited cultures 24 h after
      elicitation, and a 14-fold increase over elicited cells incubated with 2%
      glucose. Enhanced glucose uptake depended on NADPH oxidase and calcium influx,
      but not MAPK. In contrast, the increase of glucose transport activity induced by
      sugar starvation was dependent on the activation of MAPK but not NADPH oxidase.
      Both responses appeared to be dependent on de novo transcription and protein
      synthesis.

PMID- 16407394
TI  - Development of an integrated diabetes prevention program with First Nations in
      Canada.
AB  - Type 2 diabetes mellitus is a major cause of morbidity and mortality among First
      Nations in Canada. We used multiple research methods to develop an integrated
      multi-institutional diabetes prevention program based on the successful Sandy
      Lake Health and Diabetes Project and Apache Healthy Stores programs. In-depth
      interviews, a structured survey, demonstration and feedback sessions, group
      activities, and meetings with key stakeholders were used to generate knowledge
      about the needs and resources for each community, and to obtain feedback on SLHDP
      interventions. First Nations communities were eager to address the increasing
      epidemic of diabetes. Educating children through a school prevention program was
      the most popular proposed intervention. Remote communities had poorer access to
      healthy foods and more on-reserve media and services than the smaller semi-remote
      reserves. While the reserves shared similar risk factors for diabetes, variations
      in health beliefs and attitudes and environmental conditions required tailoring
      of programs to each reserve. In addition, it was necessary to balance community
      input with proven health promotion strategies. This study demonstrates the
      importance of formative research in developing integrated health promotion
      programs for multiple communities based on previously evaluated studies.

PMID- 16407395
TI  - Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced
      body size.
AB  - Although the mechanisms regulating the formation of embryonic skeletal muscle in
      vertebrates are well characterized, less is known about postnatal muscle
      formation even though the largest increases in skeletal muscle mass occur after
      birth. Adult muscle stem cells (satellite cells) appear to recapitulate the
      events that occur in embryonic myoblasts. In particular, the myogenic basic helix
      loop-helix factors, which have crucial functions in embryonic muscle development,
      are assumed to have similar roles in postnatal muscle formation. Here, we test
      this assumption by determining the role of the myogenic regulator myogenin in
      postnatal life. Because Myog-null mice die at birth, we generated mice with
      floxed alleles of Myog and mated them to transgenic mice expressing Cre
      recombinase to delete Myog before and after embryonic muscle development.
      Removing myogenin before embryonic muscle development resulted in myofiber
      deficiencies identical to those observed in Myog-null mice. However, mice in
      which Myog was deleted following embryonic muscle development had normal skeletal
      muscle, except for modest alterations in the levels of transcripts encoding Mrf4
      (Myf6) and Myod1 (MyoD). Notably, Myog-deleted mice were 30% smaller than control
      mice, suggesting that the absence of myogenin disrupted general body growth. Our
      results suggest that postnatal skeletal muscle growth is controlled by mechanisms
      distinct from those occurring in embryonic muscle development and uncover an
      unsuspected non-cell autonomous role for myogenin in the regulation of tissue
      growth.

PMID- 16407396
TI  - Granulosa cells regulate intracellular pH of the murine growing oocyte via gap
      junctions: development of independent homeostasis during oocyte growth.
AB  - Oocytes grow within ovarian follicles in which the oocyte is coupled to the
      surrounding granulosa cells by gap junctions. It was previously found that small
      growing oocytes isolated from juvenile mice and freed of their surrounding
      granulosa cells (denuded) lacked the ability to regulate their intracellular pH
      (pH(i)), did not exhibit the pH(i)-regulatory HCO(3)(-)/Cl(-) and Na(+)/H(+)
      exchange activities found in fully-grown oocytes, and had low pH(i). However,
      both exchangers became active as oocytes grew near to full size, and,
      simultaneously, oocyte pH(i) increased by approximately 0.25 pH units. Here, we
      show that, in the more physiological setting of the intact follicle, oocyte pH(i)
      is instead maintained at approximately 7.2 throughout oocyte development, and the
      growing oocyte exhibits HCO(3)(-)/Cl(-) exchange, which it lacks when denuded.
      This activity in the oocyte requires functional gap junctions, as gap junction
      inhibitors eliminated HCO(3)(-)/Cl(-) exchange activity from follicle-enclosed
      growing oocytes and substantially impeded the recovery of the oocyte from an
      induced alkalosis, implying that oocyte pH(i) may be regulated by pH-regulatory
      exchangers in granulosa cells via gap junctions. This would require robust
      HCO(3)(-)/Cl(-) exchange activity in the granulosa cells, which was confirmed
      using oocytectomized (OOX) cumulus-oocyte complexes. Moreover, in cumulus-oocyte
      complexes with granulosa cells coupled to fully-grown oocytes, HCO(3)(-)/Cl(-)
      exchange activity was identical in both compartments and faster than in denuded
      oocytes. Taken together, these results indicate that growing oocyte pH(i) is
      controlled by pH-regulatory mechanisms residing in the granulosa cells until the
      oocyte reaches a developmental stage where it becomes capable of carrying out its
      own homeostasis.

PMID- 16407397
TI  - A functional screen for sonic hedgehog regulatory elements across a 1 Mb interval
      identifies long-range ventral forebrain enhancers.
AB  - The secreted protein sonic hedgehog (Shh) plays an integral role in forming the
      ventral midline of the vertebrate central nervous system (CNS). In the absence of
      Shh function, ventral midline development is perturbed resulting in
      holoprosencephaly (HPE), a structural malformation of the brain, as well as in
      neuronal patterning and path finding defects along the length of the
      anteroposterior neuraxis. Central to the understanding of ventral neural tube
      development is how Shh transcription is regulated in the CNS. To address this
      issue, we devised an enhancer trap assay to systematically screen 1 Mb of DNA
      surrounding the Shh locus for the ability to target reporter gene expression to
      sites of Shh transcription in transgenic mouse embryos. This analysis uncovered
      six enhancers distributed over 400 kb, the combined activity of which covered all
      sites of Shh expression in the mouse embryonic CNS from the ventral forebrain to
      the posterior extent of the spinal cord. To evaluate the relative contribution of
      these enhancers to the overall pattern of Shh expression, individual elements
      were deleted in the context of a transgenic Bac reporter assay. Redundant
      mechanisms were found to control Shh-like reporter activity in the ventral spinal
      cord, hindbrain and regions of the telencephalon, whereas unique elements
      regulated Shh-like expression in the ventral midbrain, the majority of the
      ventral diencephalon and parts of the telencephalon. Three ventral forebrain
      enhancers locate on the distal side of translocation breakpoints that occurred
      upstream of Shh in human cases of HPE, suggesting that displacement of these
      regulatory elements from the Shh promoter is a likely cause of HPE in these
      individuals.

PMID- 16407399
TI  - Motoneurons and oligodendrocytes are sequentially generated from neural stem
      cells but do not appear to share common lineage-restricted progenitors in vivo.
AB  - Olig gene expression is proposed to mark the common progenitors of motoneurons
      and oligodendrocytes. In an attempt to further dissect the in vivo lineage
      relationships between motoneurons and oligodendrocytes, we used a conditional
      cell-ablation approach to kill Olig-expressing cells. Although differentiated
      motoneurons and oligodendrocytes were eliminated, our ablation study revealed a
      continuous generation and subsequent death of their precursors. Most remarkably,
      a normal number of oligodendrocyte precursors are formed at day 12 of mouse
      development, after all motoneuron precursors have been killed. The data presented
      herein supports a sequential model in which motoneuron and oligodendrocyte
      precursors are sequentially generated in vivo from neuroepithelial stem cells,
      but do not share a common lineage-restricted progenitor.

PMID- 16407398
TI  - Human trophoblast survival at low oxygen concentrations requires
      metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.
AB  - Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the
      placenta during normal pregnancy, is down regulated in pre-eclampsia, a human
      pregnancy disorder associated with poor trophoblast differentiation and survival.
      This growth factor protects against apoptosis during stress, suggesting a role in
      trophoblast survival in the relatively low O(2) ( approximately 2%) environment
      of the first trimester conceptus. Using a well-characterized human first
      trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2)
      upregulates HBEGF synthesis and secretion independently of an increase in its
      mRNA. Five other expressed members of the EGF family are largely unaffected. At
      2% O(2), signaling via HER1 or HER4, known HBEGF receptors, is required for both
      HBEGF upregulation and protection against apoptosis. This positive-feedback loop
      is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF
      ectodomain. The restoration of trophoblast survival by the addition of soluble
      HBEGF in cultures exposed to low O(2) and metalloproteinase inhibitor suggests
      that the effects of HBEGF are mediated by autocrine/paracrine, rather than
      juxtacrine, signaling. Our results provide evidence that a post-transcriptional
      mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling
      to inhibit apoptosis. These findings have a high clinical significance, as the
      downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor
      leading to the demise of trophoblasts.

PMID- 16407400
TI  - Inhibition of germline proliferation during C. elegans dauer development requires
      PTEN, LKB1 and AMPK signalling.
AB  - In C. elegans, reduced insulin-like signalling induces developmental quiescence,
      reproductive delay and lifespan extension. We show here that the C. elegans
      orthologues of LKB1 and AMPK cooperate during conditions of reduced insulin-like
      signalling to establish cell cycle quiescence in the germline stem cell
      population, in addition to prolonging lifespan. The inactivation of either
      protein causes aberrant germline proliferation during diapause-like ;dauer'
      development, whereas the loss of AMPK uncouples developmental arrest from
      lifespan extension. Reduced TGF-beta activity also triggers developmental
      quiescence independent of the insulin-like pathway. Our data suggest that these
      two signalling pathways converge on the C. elegans PTEN orthologue to coordinate
      germline proliferation with somatic development during dauer formation, via the
      regulation of AMPK and its upstream activator LKB1, rather than through the
      canonical insulin-like signalling cascade. In humans, germline mutations in TGF
      beta family members, PTEN or LKB1 result in related tumour-predisposing
      syndromes. Our findings establish a developmental relationship that may
      underscore their shared, characteristic aetiology.

PMID- 16407401
TI  - PGAP2 is essential for correct processing and stable expression of GPI-anchored
      proteins.
AB  - Biosynthesis of glycosylphosphatidylinositol-anchored proteins (GPI-APs) in the
      ER has been extensively studied, whereas the molecular events during the
      transport of GPI-APs from the ER to the cell surface are poorly understood. Here,
      we established new mutant cell lines whose surface expressions of GPI-APs were
      greatly decreased despite normal biosynthesis of GPI-APs in the ER. We identified
      a gene responsible for this defect, designated PGAP2 (for Post-GPI-Attachment to
      Proteins 2), which encoded a Golgi/ER-resident membrane protein. The low surface
      expression of GPI-APs was due to their secretion into the culture medium. GPI-APs
      were modified/cleaved by two reaction steps in the mutant cells. First, the GPI
      anchor was converted to lyso-GPI before exiting the trans-Golgi network. Second,
      lyso-GPI-APs were cleaved by a phospholipase D after transport to the plasma
      membrane. Therefore, PGAP2 deficiency caused transport to the cell surface of
      lyso-GPI-APs that were sensitive to a phospholipase D. These results demonstrate
      that PGAP2 is involved in the processing of GPI-APs required for their stable
      expression at the cell surface.

PMID- 16407402
TI  - Control of Bro1-domain protein Rim20 localization by external pH, ESCRT
      machinery, and the Saccharomyces cerevisiae Rim101 pathway.
AB  - Bro1-domain proteins such as yeast Bro1 and mammalian AIP1/Alix are well
      established participants in endosome metabolism. The Bro1-domain interacts with
      endosomal surface protein Snf7/Vps32 in yeast, a subunit of the ESCRT complex.
      Yeast Bro1-domain protein Rim20 has no role in endosome function, but is required
      for alkaline pH-stimulated cleavage of transcription factor Rim101. Rim20-GFP is
      cytoplasmic under acidic conditions but concentrated in punctate foci under
      alkaline conditions. Bro1-GFP also accumulates in foci, but they are more
      numerous under acidic than alkaline conditions. Colocalization experiments
      indicate that some Rim20-GFP foci correspond to Bro1-RFP foci, whereas others do
      not. Rim8, Rim9, Rim21, Dfg16, Snf7, Vps20, Vps23, and Vps25, which are required
      for Rim101 cleavage, are required for appearance of Rim20-GFP foci. ESCRT
      complexes accumulate on endosome-derived compartments in cells that lack the AAA
      ATPase Vps4. We find that Rim20-GFP foci accumulate in a vps4 mutant background
      independently of external pH, Rim101 pathway-specific genes, and most ESCRT
      subunit genes except for SNF7. Rim20-GFP foci seem to represent endosomes,
      because they colocalize with Snf7-RFP and because they correspond to a
      perivacuolar compartment in the vps4 strain. We propose that alkaline growth
      conditions alter the endosomal surface to favor Rim20-Snf7 interaction and Rim101
      cleavage. Our findings raise the possibility that Bro1-domain proteins may be
      differentially regulated in the same cell, thereby coupling endosome metabolism
      to signaling.

PMID- 16407403
TI  - An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1:
      evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins.
AB  - Sorting nexin 1 (SNX1) and SNX2 are the mammalian homologues of the yeast Vps5p
      retromer component that functions in endosome-to-Golgi trafficking. SNX1 is also
      implicated in endosome-to-lysosome sorting of cell surface receptors, although
      its requirement in this process remains to be determined. To assess SNX1 function
      in endocytic sorting of protease-activated receptor-1 (PAR1), we used siRNA to
      deplete HeLa cells of endogenous SNX1 protein. PAR1, a G-protein-coupled
      receptor, is proteolytically activated by thrombin, internalized, sorted
      predominantly to lysosomes, and efficiently degraded. Strikingly, depletion of
      endogenous SNX1 by siRNA markedly inhibited agonist-induced PAR1 degradation,
      whereas expression of a SNX1 siRNA-resistant mutant protein restored agonist
      promoted PAR1 degradation in cells lacking endogenous SNX1, indicating that SNX1
      is necessary for lysosomal degradation of PAR1. SNX1 is known to interact with
      components of the mammalian retromer complex and Hrs, an early endosomal membrane
      associated protein. However, activated PAR1 degradation was not affected in cells
      depleted of retromer Vps26/Vps35 subunits, Hrs or Tsg101, an Hrs-interacting
      protein. We further show that SNX2, which dimerizes with SNX1, is not essential
      for lysosomal sorting of PAR1, but rather can regulate PAR1 degradation by
      disrupting endosomal localization of endogenous SNX1 when ectopically expressed.
      Together, our findings establish an essential role for endogenous SNX1 in sorting
      activated PAR1 to a distinct lysosomal degradative pathway that is independent of
      retromer, Hrs, and Tsg101.

PMID- 16407404
TI  - Conditional dominant mutations in the Caenorhabditis elegans gene act-2 identify
      cytoplasmic and muscle roles for a redundant actin isoform.
AB  - Animal genomes each encode multiple highly conserved actin isoforms that
      polymerize to form the microfilament cytoskeleton. Previous studies of
      vertebrates and invertebrates have shown that many actin isoforms are restricted
      to either nonmuscle (cytoplasmic) functions, or to myofibril force generation in
      muscle cells. We have identified two temperature-sensitive and semidominant
      embryonic-lethal Caenorhabditis elegans mutants, each with a single mis-sense
      mutation in act-2, one of five C. elegans genes that encode actin isoforms. These
      mutations alter conserved and adjacent amino acids predicted to form part of the
      ATP binding pocket of actin. At the restrictive temperature, both mutations
      resulted in aberrant distributions of cortical microfilaments associated with
      abnormal and striking membrane ingressions and protrusions. In contrast to the
      defects caused by these dominant mis-sense mutations, an act-2 deletion did not
      result in early embryonic cell division defects, suggesting that additional and
      redundant actin isoforms are involved. Accordingly, we found that two additional
      actin isoforms, act-1 and act-3, were required redundantly with act-2 for
      cytoplasmic function in early embryonic cells. The act-1 and -3 genes also have
      been implicated previously in muscle function. We found that an ACT-2::GFP
      reporter was expressed cytoplasmically in embryonic cells and also was
      incorporated into contractile filaments in adult muscle cells. Furthermore, one
      of the dominant act-2 mutations resulted in uncoordinated adult movement. We
      conclude that redundant C. elegans actin isoforms function in both muscle and
      nonmuscle contractile processes.

PMID- 16407406
TI  - Differential distribution of exosome subunits at the nuclear lamina and in
      cytoplasmic foci.
AB  - The exosome complex plays important roles in RNA processing and turnover. Despite
      significant mechanistic insight into exosome function, we still lack a basic
      understanding of the subcellular locales where exosome complex biogenesis and
      function occurs. Here, we employ a panel of Drosophila S2 stable cell lines
      expressing epitope-tagged exosome subunits to examine the subcellular
      distribution of exosome complex components. We show that tagged Drosophila
      exosome subunits incorporate into complexes that recover endogenous nuclear and
      cytoplasmic exosome subunits. Immunolocalization analyses demonstrate that
      subsets of both epitope-tagged and endogenous exosome subunits are enriched in
      discrete subcellular compartments. In particular, dRrp4, dRrp42, dRrp46, and
      dCsl4 are enriched in cytoplasmic foci. Although dRrp4 and dRrp42 sometimes
      colocalize with dCsl4, these subunits are predominantly found in distinct
      cytoplasmic compartments. Strikingly, dRrp44/dDis3 and dRrp41/dSki6 colocalize
      with the nuclear lamina and often exhibit a restricted and asymmetric
      distribution at the nuclear periphery. Taken together, these observations
      indicate that individual exosome subunits have distinct localizations in vivo.
      These different distribution patterns presumably reflect distinct exosome subunit
      subcomplexes with correspondingly specialized functions.

PMID- 16407405
TI  - Cip1 and Cip2 are novel RNA-recognition-motif proteins that counteract Csx1
      function during oxidative stress.
AB  - Eukaryotic cells reprogram their global patterns of gene expression in response
      to stress. Recent studies in Schizosaccharomyces pombe showed that the RNA
      binding protein Csx1 plays a central role in controlling gene expression during
      oxidative stress. It does so by stabilizing atf1(+) mRNA, which encodes a subunit
      of a bZIP transcription factor required for gene expression during oxidative
      stress. Here, we describe two related proteins, Cip1 and Cip2, that were
      identified by multidimensional protein identification technology (MudPIT) as
      proteins that coprecipitate with Csx1. Cip1 and Cip2 are cytoplasmic proteins
      that have RNA recognition motifs (RRMs). Neither protein is essential for
      viability, but a cip1Delta cip2Delta strain grows poorly and has altered cellular
      morphology. Genetic epistasis studies and whole genome expression profiling show
      that Cip1 and Cip2 exert posttranscriptional control of gene expression in a
      manner that is counteracted by Csx1. Notably, the sensitivity of csx1Delta cells
      to oxidative stress and their inability to induce expression of Atf1-dependent
      genes are partially rescued by cip1Delta and cip2Delta mutations. This study
      emphasizes the importance of a modulated mRNA stability in the eukaryotic stress
      response pathways and adds new information to the role of RNA-binding proteins in
      the oxidative stress response.

PMID- 16407407
TI  - Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation
      of a subclass of preproteins.
AB  - Mitochondria consist of four compartments-outer membrane, intermembrane space,
      inner membrane, and matrix--with crucial but distinct functions for numerous
      cellular processes. A comprehensive characterization of the proteome of an
      individual mitochondrial compartment has not been reported so far. We used a
      eukaryotic model organism, the yeast Saccharomyces cerevisiae, to determine the
      proteome of highly purified mitochondrial outer membranes. We obtained a coverage
      of approximately 85% based on the known outer membrane proteins. The proteome
      represents a rich source for the analysis of new functions of the outer membrane,
      including the yeast homologue (Hfd1/Ymr110c) of the human protein causing Sjogren
      Larsson syndrome. Surprisingly, a subclass of proteins known to reside in
      internal mitochondrial compartments were found in the outer membrane proteome.
      These seemingly mislocalized proteins included most top scorers of a recent
      genome-wide analysis for mRNAs that were targeted to mitochondria and coded for
      proteins of prokaryotic origin. Together with the enrichment of the precursor
      form of a matrix protein in the outer membrane, we conclude that the
      mitochondrial outer membrane not only contains resident proteins but also
      accumulates a conserved subclass of preproteins destined for internal
      mitochondrial compartments.

PMID- 16407408
TI  - Survivin modulates microtubule dynamics and nucleation throughout the cell cycle.
AB  - Survivin is a member of the chromosomal passenger complex implicated in
      kinetochore attachment, bipolar spindle formation, and cytokinesis. However, the
      mechanism by which survivin modulates these processes is unknown. Here, we show
      by time-lapse imaging of cells expressing either green fluorescent protein (GFP)
      alpha-tubulin or the microtubule plus-end binding protein GFP-EB1 that depletion
      of survivin by small interfering RNAs (siRNAs) increased both the number of
      microtubules nucleated by centrosomes and the incidence of microtubule
      catastrophe, the transition from microtubule growth to shrinking. In contrast,
      survivin overexpression reduced centrosomal microtubule nucleation and suppressed
      both microtubule dynamics in mitotic spindles and bidirectional growth of
      microtubules in midbodies during cytokinesis. siRNA depletion or pharmacologic
      inhibition of another chromosomal passenger protein Aurora B, had no effect on
      microtubule dynamics or nucleation in interphase or mitotic cells even though
      mitosis was impaired. We propose a model in which survivin modulates several
      mitotic events, including spindle and interphase microtubule organization, the
      spindle assembly checkpoint and cytokinesis through its ability to modulate
      microtubule nucleation and dynamics. This pathway may affect the microtubule
      dependent generation of aneuploidy and defects in cell polarity in cancer cells,
      where survivin is commonly up-regulated.

PMID- 16407409
TI  - Identification of the junctional plaque protein plakophilin 3 in cytoplasmic
      particles containing RNA-binding proteins and the recruitment of plakophilins 1
      and 3 to stress granules.
AB  - Recent studies on the subcellular distribution of cytoplasmic plaque proteins of
      intercellular junctions have revealed that a number of such proteins can also
      occur in the cyto- and the nucleoplasm. This occurrence in different, and distant
      locations suggest that some plaque proteins play roles in cytoplasmic and nuclear
      processes in addition to their involvement in cell-cell adhesive interactions.
      Plakophilin (PKP) 3, a member of the arm-repeat family of proteins, occurs, in a
      diversity of cell types, both as an architectural component in plaques of
      desmosomes and dispersed in cytoplasmic particles. In immuno-selection
      experiments using PKP3-specific antibodies, we have identified by mass
      spectrometric analysis the following RNA-binding proteins: Poly (A) binding
      protein (PABPC1), fragile-X-related protein (FXR1), and ras-GAP-SH3-binding
      protein (G3BP). Moreover, the RNA-binding proteins codistributed after sucrose
      gradient centrifugation in PKP3-containing fractions corresponding to 25-35 S and
      45-55 S. When cells are exposed to environmental stress (e.g., heat shock or
      oxidative stress) proteins FXR1, G3BP, and PABPC1 are found, together with PKP3
      or PKP1, in "stress granules" known to accumulate stalled translation initiation
      complexes. Moreover, the protein eIF-4E and the ribosomal protein S6 are also
      detected in PKP3 particles. Our results show that cytoplasmic PKP3 is
      constitutively associated with RNA-binding proteins and indicate an involvement
      in processes of translation and RNA metabolism.

PMID- 16407410
TI  - The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and
      regulates transcriptional activity of ZONAB.
AB  - The tight junction adaptor protein ZO-1 regulates intracellular signaling and
      cell proliferation. Its Src homology 3 (SH3) domain is required for the
      regulation of proliferation and binds to the Y-box transcription factor ZO-1
      associated nucleic acid binding protein (ZONAB). Binding of ZO-1 to ZONAB results
      in cytoplasmic sequestration and hence inhibition of ZONAB's transcriptional
      activity. Here, we identify a new binding partner of the SH3 domain that
      modulates ZO-1-ZONAB signaling. Expression screening of a cDNA library with a
      fusion protein containing the SH3 domain yielded a cDNA coding for Apg-2, a
      member of the heat-shock protein 110 (Hsp 110) subfamily of Hsp70 heat-shock
      proteins, which is overexpressed in carcinomas. Regulated depletion of Apg-2 in
      Madin-Darby canine kidney cells inhibits G(1)/S phase progression. Apg-2
      coimmunoprecipitates with ZO-1 and partially localizes to intercellular
      junctions. Junctional recruitment and coimmunoprecipitation with ZO-1 are
      stimulated by heat shock. Apg-2 competes with ZONAB for binding to the SH3 domain
      in vitro and regulates ZONAB's transcriptional activity in reporter gene assays.
      Our data hence support a model in which Apg-2 regulates ZONAB function by
      competing for binding to the SH3 domain of ZO-1 and suggest that Apg-2 functions
      as a regulator of ZO-1-ZONAB signaling in epithelial cells in response to
      cellular stress.

PMID- 16407411
TI  - Chromokinesin Xklp1 contributes to the regulation of microtubule density and
      organization during spindle assembly.
AB  - Xklp1 is a chromosome-associated kinesin required for Xenopus early embryonic
      cell division. Function blocking experiments in Xenopus egg extracts suggested
      that it is required for spindle assembly. We have reinvestigated Xklp1
      function(s) by monitoring spindle assembly and microtubule behavior under a range
      of Xklp1 concentrations in egg extracts. We found that in the absence of Xklp1,
      bipolar spindles form with a reduced efficiency and display abnormalities
      associated with an increased microtubule mass. Likewise, centrosomal asters
      assembled in Xklp1-depleted extract show an increased microtubule mass.
      Conversely, addition of recombinant Xklp1 to the extract reduces the microtubule
      mass associated with spindles and asters. Our data suggest that Xklp1 affects
      microtubule polymerization during M-phase. We propose that these attributes,
      combined with Xklp1 plus-end directed motility, contribute to the assembly of a
      functional bipolar spindle.

PMID- 16407413
TI  - Resident stem cells are not required for exercise-induced fiber-type switching
      and angiogenesis but are necessary for activity-dependent muscle growth.
AB  - Skeletal muscle undergoes active remodeling in response to endurance exercise
      training, and the underlying mechanisms of this remodeling remain to be defined
      fully. We have recently obtained evidence that voluntary running induces cell
      cycle gene expression and cell proliferation in mouse plantaris muscles that
      undergo fast-to-slow fiber-type switching and angiogenesis after long-term
      exercise. To ascertain the functional role of cell proliferation in skeletal
      muscle adaptation, we performed in vivo 5-bromo-2'-deoxyuridine (BrdU) pulse
      labeling (a single intraperitoneal injection), which demonstrated a phasic
      increase (5- to 10-fold) in BrdU-positive cells in plantaris muscle between days
      3 and 14 during 4 wk of voluntary running. Daily intraperitoneal injection of
      BrdU for 4 wk labeled 2.0% and 15.4% of the nuclei in plantaris muscle in
      sedentary and trained mice, respectively, and revealed the myogenic and
      angiogenic fates of the majority of proliferative cells. Ablation of resident
      stem cell activity by X-ray irradiation did not prevent voluntary running-induced
      increases of type IIa myofibers and CD31-positive endothelial cells but
      completely blocked the increase in muscle mass. These findings suggest that
      resident stem cell proliferation is not required for exercise-induced type IIb-to
      IIa fiber-type switching and angiogenesis but is required for activity-dependent
      muscle growth. The origin of the angiogenic cells in this physiological exercise
      model remains to be determined.

PMID- 16407414
TI  - Ca2+-sensing receptor induces Rho kinase-mediated actin stress fiber assembly and
      altered cell morphology, but not in response to aromatic amino acids.
AB  - The Ca2+-sensing receptor (CaR) is a pleiotropic, type III G protein-coupled
      receptor (GPCR) that associates functionally with the cytoskeletal protein
      filamin. To investigate the effect of CaR signaling on the cytoskeleton, human
      embryonic kidney (HEK)-293 cells stably transfected with CaR (CaR-HEK) were
      incubated with CaR agonists in serum-free medium for up to 3 h. Addition of the
      calcimimetic NPS R-467 or exposure to high extracellular Ca2+ or Mg2+ levels
      elicited actin stress fiber assembly and process retraction in otherwise stellate
      cells. These responses were ablated by cotreatment with the calcilytic NPS 89636
      and were absent in vector-transfected HEK-293 cells. Cotreatment with the Rho
      kinase inhibitors Y-27632 and H1152 attenuated the CaR-induced morphological
      change but not intracellular Ca2+ (Ca2+(i)) mobilization or ERK activation,
      although transfection with a dominant-negative RhoA-binding protein also
      inhibited calcimimetic-induced actin stress fiber assembly. CaR effects on
      morphology were unaffected by inhibition of G(q/11) or G(i/o) signaling,
      epidermal growth factor receptor, or the metalloproteinases. In contrast, CaR
      induced cytoskeletal changes were not induced by the aromatic amino acids,
      treatments that also failed to potentiate CaR-induced ERK activation despite
      inducing Ca2+(i) mobilization. Together, these data establish that CaR can elicit
      Rho-mediated changes in stress fiber assembly and cell morphology, which could
      contribute to the receptor's physiological actions. In addition, this study
      provides further evidence that aromatic amino acids elicit differential signaling
      from other CaR agonists.

PMID- 16407412
TI  - Identification of novel in vivo Raf-1 phosphorylation sites mediating positive
      feedback Raf-1 regulation by extracellular signal-regulated kinase.
AB  - The Ras-Raf-mitogen-activated protein kinase cascade is a key growth-signaling
      pathway, which uncontrolled activation results in transformation. Although the
      exact mechanisms underlying Raf-1 regulation remain incompletely understood,
      phosphorylation has been proposed to play a critical role in this regulation. We
      report here three novel epidermal growth factor-induced in vivo Raf-1
      phosphorylation sites that mediate positive feedback Raf-1 regulation. Using mass
      spectrometry, we identified Raf-1 phosphorylation on three SP motif sites:
      S289/S296/S301 and confirmed their identity using two-dimensional-phosphopeptide
      mapping and phosphospecific antibodies. These sites were phosphorylated by
      extracellular signal-regulated kinase (ERK)-1 in vitro, and their phosphorylation
      in vivo was dependent on endogenous ERK activity. Functionally, ERK-1 expression
      sustains Raf-1 activation in a manner dependent on Raf-1 phosphorylation on the
      identified sites, and S289/296/301A substitution markedly decreases the in vivo
      activity of Raf-1 S259A. Importantly, the ERK-phosphorylated Raf-1 pool has 4
      times higher specific kinase activity than total Raf-1, and its phosphopeptide
      composition is similar to that of the general Raf-1 population, suggesting that
      the preexisting, phosphorylated Raf-1, representing the activatable Raf-1 pool,
      is the Raf-1 subpopulation targeted by ERK. Our study describes the
      identification of new in vivo Raf-1 phosphorylation sites targeted by ERK and
      provides a novel mechanism for a positive feedback Raf-1 regulation.

PMID- 16407415
TI  - Cytotoxicity of water-soluble fullerene in vascular endothelial cells.
AB  - Nanoscale materials are presently under development for diagnostic (nanomedicine)
      and electronic purposes. In contrast to the potential benefits of nanotechnology,
      the effects of nanomaterials on human health are poorly understood. Nanomaterials
      are known to translocate into the circulation and could thus directly affect
      vascular endothelial cells (ECs), causing vascular injury that might be
      responsible for the development of atherosclerosis. To explore the direct effects
      of nanomaterials on endothelial toxicity, human umbilical vein ECs were treated
      with 1-100 microg/ml hydroxyl fullerene [C60(OH)24; mean diameter, 7.1 +/- 2.4
      nm] for 24 h. C60(OH)24 induced cytotoxic morphological changes such as cytosolic
      vacuole formation and decreased cell density in a dose-dependent manner. Lactate
      dehydrogenase assay revealed that a maximal dose of C60(OH)24 (100 microg/ml)
      induced cytotoxic injury. Proliferation assay also showed that a maximal dose of
      C60(OH)24 inhibited EC growth. C60(OH)24 did not seem to induce apoptosis but
      caused the accumulation of polyubiquitinated proteins and facilitated autophagic
      cell death. Formation of autophagosomes was confirmed on the basis of Western
      blot analysis using a specific marker, light chain 3 antibody, and electron
      microscopy. Chronic treatment with low-dose C60(OH)24 (10 microg/ml for 8 days)
      inhibited cell attachment and delayed EC growth. In the present study, we have
      examined, for the first time, the toxicity of water-soluble fullerenes to ECs.
      Although fullerenes changed morphology in a dose-dependent manner, only maximal
      doses of fullerenes caused cytotoxic injury and/or death and inhibited cell
      growth. EC death seemed to be caused by activation of ubiquitin-autophagy cell
      death pathways. Although exposure to nanomaterials appears to represent a risk
      for cardiovascular disorders, further in vivo validations are necessary.

PMID- 16407416
TI  - Intrinsic mechanical properties of the extracellular matrix affect the behavior
      of pre-osteoblastic MC3T3-E1 cells.
AB  - Mechanical cues present in the ECM have been hypothesized to provide instructive
      signals that dictate cell behavior. We probed this hypothesis in osteoblastic
      cells by culturing MC3T3-E1 cells on the surface of type I collagen-modified
      hydrogels with tunable mechanical properties and assessed their proliferation,
      migration, and differentiation. On gels functionalized with a low type I collagen
      density, MC3T3-E1 cells cultured on polystyrene proliferated twice as fast as
      those cultured on the softest substrate. Quantitative time-lapse video
      microscopic analysis revealed random motility speeds were significantly retarded
      on the softest substrate (0.25 +/- 0.01 microm/min), in contrast to maximum
      speeds on polystyrene substrates (0.42 +/- 0.04 microm/min). On gels
      functionalized with a high type I collagen density, migration speed exhibited a
      biphasic dependence on ECM compliance, with maximum speeds (0.34 +/- 0.02
      microm/min) observed on gels of intermediate stiffness, whereas minimum speeds
      (0.24 +/- 0.03 microm/min) occurred on both the softest and most rigid (i.e.,
      polystyrene) substrates. Immature focal contacts and a poorly organized actin
      cytoskeleton were observed in cells cultured on the softest substrates, whereas
      those on more rigid substrates assembled mature focal adhesions and robust actin
      stress fibers. In parallel, focal adhesion kinase (FAK) activity (assessed by
      detecting pY397-FAK) was influenced by compliance, with maximal activity
      occurring in cells cultured on polystyrene. Finally, mineral deposition by the
      MC3T3-E1 cells was also affected by ECM compliance, leading to the conclusion
      that altering ECM mechanical properties may influence a variety of MC3T3-E1 cell
      functions, and perhaps ultimately, their differentiated phenotype.

PMID- 16407417
TI  - 130-kDa smooth muscle myosin light chain kinase is transcribed from a CArG
      dependent, internal promoter within the mouse mylk gene.
AB  - The 130-kDa smooth muscle myosin light chain kinase (smMLCK) is a Ca2+/CaM
      regulated enzyme that plays a pivotal role in the initiation of smooth muscle
      contraction and regulation of cellular migration and division. Despite the
      critical importance of smMLCK in these processes, little is known about the
      mechanisms regulating its expression. In this study, we have identified the
      proximal promoter of smMLCK within an intron of the mouse mylk gene. The mylk
      gene encodes at least two isoforms of MLCK (130 and 220 kDa) and telokin.
      Luciferase reporter gene assays demonstrated that a 282-bp fragment (-167 to
      +115) of the smMLCK promoter was sufficient for maximum activity in A10 smooth
      muscle cells and 10T1/2 fibroblasts. Deletion of the 16 bp between -167 and -151,
      which included a CArG box, resulted in a nearly complete loss of promoter
      activity. Gel mobility shift assays and chromatin immunoprecipitation assays
      demonstrated that serum response factor (SRF) binds to this CArG box both in
      vitro and in vivo. SRF knockdown by short hairpin RNA decreased endogenous smMLCK
      expression in A10 cells. Although the SRF coactivator myocardin induced smMLCK
      expression in 10T1/2 cells, myocardin activated the promoter only two- to
      fourfold in reporter gene assays. Addition of either intron 1 or 6 kb of the 5'
      upstream sequence did not lead to any further activation of the promoter by
      myocardin. The proximal smMLCK promoter also contains a consensus GATA-binding
      site that bound GATA-6. GATA-6 binding to this site decreased endogenous smMLCK
      expression, inhibited promoter activity in smooth muscle cells, and blocked the
      ability of myocardin to induce smMLCK expression. Altogether, these data suggest
      that SRF and SRF-associated factors play a key role in regulating the expression
      of smMLCK.

PMID- 16407418
TI  - Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine
      treated non-small-cell lung cancer patients.
AB  - BACKGROUND: Impaired DNA repair capacity may favorably affect survival in
      cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We
      investigated the association of survival with genetic polymorphisms in X-ray
      repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum
      group D (XPD), excision repair cross-complementing group 1, ligase IV,
      ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome
      proliferator-activated receptor gamma, epidermal growth factor, methylene-tetra
      hydrofolate reductase and methionine synthase. PATIENTS AND METHODS: One hundred
      and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients
      treated with cisplatin/gemcitabine from different hospitals of the Spanish Lung
      Cancer Group were genotyped for 14 different polymorphisms in 13 genes.
      Polymorphisms were detected by the TaqMan method, using genomic DNA extracted
      from baseline blood samples. RESULTS: Median survival was significantly increased
      in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients
      with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death
      ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio,
      0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent
      prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751
      and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD
      751 LysGln, 0.46, P = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other
      association was observed between genotype and survival. CONCLUSION: XRCC3 241
      MetMet is an independent determinant of favorable survival in NSCLC patients
      treated with cisplatin/gemcitabine. A simple molecular assay to determine the
      XRCC3 241 genotype can be useful for customizing chemotherapy.

PMID- 16407420
TI  - Influence of adjuvant anastrozole on bone mineral density in Japanese
      postmenopausal breast cancer patients: is there a racial difference?

PMID- 16407419
TI  - Metalloproteinase-2, -7 and -9 and tissue inhibitor of metalloproteinase-1 and -2
      expression in normal, hyperplastic and neoplastic endometrium: a clinical
      pathological correlation study.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors are key-players
      in extracellular matrix and basement membrane degradation, and are involved in
      both physiological and malignant processes. The aim of this study was to examine
      MMP-2, -7 and -9 and TIMP-1 and -2 expression in normal, hyperplastic and
      malignant endometrium, and their relation to clinical and histological prognostic
      factors. MATERIALS AND METHODS: We performed qualitative and semi-quantitative
      immunohistochemical analysis of 20 samples of normal endometrium (10 in the
      proliferative phase, 10 in the secretory phase), 39 samples of hyperplastic
      endometrium (17 without atypia and 22 with atypia) and 38 samples of endometrioid
      carcinoma, by using specific monoclonal antibodies. RESULTS: In normal
      endometrium, epithelial expression of MMP-2 (P = 0.0007), MMP-7 (P = 0.0002) and
      TIMP-2 (P = 0.0004) was increased during the proliferative phase of the menstrual
      cycle. MMP-2 expression correlated negatively with TIMP-2 expression (P = 0.001,
      rho = 0.702). Endometrial stromal cells in the secretory phase showed strong MMP
      2 expression (P = 0.004) and weak MMP-7 (P = 0.001) and TIMP-1 expression (P =
      0.01). In hyperplastic endometrium, the presence of atypia was associated with
      lower TIMP-2 expression (P = 0.005) and was also associated with a trend towards
      higher MMP-2 expression. Endometrial stromal cell expression of MMP-2, -7 and -9
      and TIMP-1 and -2 did not differ between hyperplastic endometrium with and
      without atypia. A gradient of MMP-2 and -9 expression was observed from
      hyperplastic endometrium to endometrial carcinomas. In endometrial carcinomas,
      MMP-2 expression increased (P = 0.0004) and TIMP-2 expression decreased (P =
      0.0005) with the histological grade. TIMP-2 expression correlated with myometrial
      invasion (P = 0.005), lymphovascular space involvement (P = 0.008) and lymph node
      involvement (P = 0.007). CONCLUSION: These results support the involvement of
      MMPs and TIMPs in endometrial carcinogenesis. Strong MMP-2 and weak TIMP-2
      expression were the most potent markers of endometrial malignancies with a high
      risk of local and distant spread.

PMID- 16407421
TI  - Diabetic nephropathy: a frontier for personalized medicine.
AB  - Diabetic nephropathy (DNP) develops after latency periods that may vary by
      several years in approximately one third of patients with diabetes. This diabetic
      complication is a complex disorder whereby various genetic and environmental
      factors determine susceptibility and progression to ESRD. Despite rapid research
      progress, robust predictors to assess prospectively with high precision the risk
      for DNP in individuals with diabetes are still lacking. Thus, currently available
      therapies are usually initiated at more advanced stages of DNP characterized by
      clinically overt manifestations, including increased urinary albumin excretion
      and decreased glomerular filtration. In addition, although these interventions
      have proven efficacy in slowing the progression of DNP, they typically cannot
      prevent ESRD. New insights into the molecular mechanisms that underlie the origin
      and progression of DNP are emerging rapidly from advanced large-scale genetic and
      molecular studies in experimental models and humans. Thus, genetic loci that
      confer risk for albuminuria and/or progression of kidney disease associated with
      diabetes are being refined to identify the relevant genetic variants in specific
      genes. Molecular mRNA profiles that are obtained through microarray screens are
      being validated to elucidate further their potential as molecular markers and to
      identify new targets for novel preventive or therapeutic approaches aiming at
      curing DNP. The challenge before the field is to translate the large amount of
      new genetic and molecular data to empower clinicians and investigators with
      reliable predictors of DNP for improved design of preventive clinical trials and
      for individualized clinical management for millions of individuals affected by
      diabetes worldwide.

PMID- 16407422
TI  - Changes in cortically related intermuscular coherence accompanying improvements
      in locomotor skills in incomplete spinal cord injury.
AB  - In human spinal cord injury, the neuronal mechanisms mediating the improvement of
      locomotor function in response to intensive treadmill training are not well
      understood. In this study, we examined if such recovery is mediated, in part, by
      increases in residual corticospinal drive to muscles of the leg during walking.
      To do this, we measured the coherence of electromyogram (EMG) activity between
      two antagonist muscles (intermuscular coherence), specifically at frequencies
      between 24 and 40 Hz, which is thought to indicate common drive to two muscles
      from corticospinal inputs. In 12 subjects with incomplete spinal cord injury,
      intermuscular coherence was measured between hamstrings and vastus lateralis EMG
      that was activated during walking on a motorized treadmill. Before training,
      appreciable coherence in the 24-40 Hz frequency band was only present in subjects
      with moderate volitional motor strength in their leg muscles (n = 8 subjects)
      compared with subjects with little or no leg muscle strength (n = 4 subjects),
      reconfirming that 24-40 Hz frequency coherence is likely mediated by common
      supraspinal inputs. After training, increases in 24-40 Hz coherence only occurred
      in the eight subjects with moderate leg muscle strength who also exhibited
      improvements in locomotor recovery as assessed by the 21 point WISCI II scale
      (termed responders). In contrast, development of intermuscular coherence in the
      24-40 Hz frequency band did not occur in the four subjects with absent or weak
      muscle strength. These subjects also did not improve in their locomotor ability
      as reflected in unchanging WISCI II scores (termed nonresponders). Lower
      frequency coherence (5-18 Hz), which is thought to contain common drive from
      spinal inputs, did not change in either group. In a subset of subjects that were
      previously assessed with transcranial magnetic stimulation (TMS) before and after
      training (n = 5 responders and 3 nonresponders), there was a significant and
      positive relationship between increases in 24-40 Hz coherence and increases in
      evoked muscle responses to TMS of the primary motor cortex. Taken together,
      increases in higher-frequency EMG coherence in subjects with residual voluntary
      muscle strength and its parallel relation to changes in TMS-evoked responses
      provides further evidence that improvements in locomotor function from treadmill
      training are mediated, in part, by increases in corticospinal drive to muscles of
      the leg during walking.

PMID- 16407423
TI  - Retention of adaptive control over varying intervals: prevention of slip- induced
      backward balance loss during gait.
AB  - Stability improvements made in a single acquisition session with merely five
      slips in walking are sufficient to prevent backward balance loss (BLOB) at the
      end of session, but not after 12 mo. The purpose of this study was to determine
      whether the effect of an enhanced single acquisition session would be retainable
      if tested sooner, at intervals of < or =4 mo. Twenty-four young subjects were
      exposed to blocks of slip, nonslip, and both types of trials during walking at
      their preferred speed in the acquisition session. In each of the four follow-up
      sessions around 1 wk, 2 wk, 1 mo, and 4 mo later, these same subjects experienced
      only a single slip after eight to 13 unperturbed walking trials in an otherwise
      identical setup. Gait stability was obtained as the shortest distance between the
      measured center of mass (COM) state (position and velocity) and the
      mathematically predicted threshold for BLOB at pre- and postslip, corresponding
      to the instants of touchdown of the slipping limb and liftoff of the
      contralateral limb, respectively. During the acquisition session, pre- and
      postslip stability improved significantly, resulting in a reduction of BLOB from
      100% in the first slip (S1) to 0% in the last slip (S24), with improvements
      converging to a steady state, that enabled all of the subjects to avoid BLOB,
      regardless of whether a slip occurred. During retest sessions, subjects' preslip
      stability was not different from that in S24, but was greater than that in S1.
      Their postslip stability was also greater than that in S1 but less than that in
      S24, resulting in BLOB at a 40% level. No difference was found in any of these
      aspects between each follow-up session. These adaptive changes were associated
      with a range of individual differences, varying from no detectable deterioration
      in all aspects (n = 8) to a consistent BLOB in all follow-ups (n = 3). Our
      findings demonstrated the extent of plasticity of the CNS, characterized by rapid
      acquisition of a stable COM state under unpredictable slip conditions and
      retention of such improvements for months, resulting in a reduced occurrence of
      unintended backward falling.

PMID- 16407425
TI  - Development of saccadic suppression in children.
AB  - We measured saccadic suppression in adolescent children and young adults using
      spatially curtailed low spatial frequency stimuli. For both groups, sensitivity
      for color-modulated stimuli was unchanged during saccades. Sensitivity for
      luminance-modulated stimuli was greatly reduced during saccades in both groups
      but far more for adolescents than for young adults. Adults' suppression was on
      average a factor of about 3, whereas that for the adolescent group was closer to
      a factor of 10. The specificity of the suppression to luminance-modulated stimuli
      excludes generic explanations such as task difficulty and attention. We suggest
      that the enhanced suppression in adolescents results from the immaturity of the
      ocular-motor system at that age.

PMID- 16407426
TI  - GABAA receptor-mediated IPSCs and alpha1 subunit expression are not reduced in
      the substantia nigra pars reticulata of gerbils with inherited epilepsy.
AB  - Domestic Mongolian gerbils, a model of inherited epilepsy, begin having
      spontaneous seizures at approximately 1.5 mo of age, making it possible to
      evaluate them during epileptic and pre-epileptic stages. Previous studies have
      shown that GABA binding is reduced in the substantia nigra pars reticulata (SNr)
      of both epileptic and pre-epileptic gerbils compared with controls, suggesting
      that reduced expression of GABAA receptors in SNr might be epileptogenic in this
      model. To test this hypothesis, we measured the expression of the GABAA receptor
      alpha1 subunit, the dominant alpha subunit expressed in the SNr, and evaluated
      GABAA receptor-mediated postsynaptic currents in SNr neurons. GABA(A) alpha1
      subunit mRNA levels in substantia nigra-rich tissue from pre-epileptic animals
      were similar to controls, and immunocytochemistry for the alpha1 subunit showed
      similar strong expression in the SNr in both groups. Western analysis confirmed
      that expression of the alpha1 subunit protein was similar in substantia nigra
      rich tissue from pre-epileptic and control gerbils. The frequency and amplitude
      of spontaneous inhibitory postsynaptic currents (IPSCs) and the frequency of
      miniature (m)IPSCs in SNr neurons of pre-epileptic gerbil were similar to those
      of controls. The amplitude of mIPSCs in the pre-epileptics was significantly
      larger than controls. Zolpidem, an alpha1 subunit-specific modulator of the GABAA
      receptor, was equally efficacious in prolonging the decay time of mIPSCs in both
      groups. Hence, contrary to the predictions of the hypothesis, mRNA and protein
      expression levels of the major GABAA receptor alpha subunit were normal, and
      neurons of the SNr in pre-epileptic gerbils displayed normal or enhanced IPSC
      frequencies and amplitudes. Therefore reduced expression of GABAA receptors in
      SNr is not likely to be an epileptogenic mechanism in this model.

PMID- 16407424
TI  - Musculoskeletal plasticity after acute spinal cord injury: effects of long-term
      neuromuscular electrical stimulation training.
AB  - Maintaining the physiologic integrity of paralyzed limbs may be critical for
      those with spinal cord injury (SCI) to be viable candidates for a future cure. No
      long-term intervention has been tested to attempt to prevent the severe
      musculoskeletal deterioration that occurs after SCI. The purposes of this study
      were to determine whether a long-term neuromuscular electrical stimulation
      training program can preserve the physiological properties of the plantar flexor
      muscles (peak torque, fatigue index, torque-time integral, and contractile speed)
      as well as influence distal tibia trabecular bone mineral density (BMD). Subjects
      began unilateral plantar flexion electrical stimulation training within 6 wk
      after SCI while the untrained leg served as a control. Mean compliance for the 2
      yr training program was 83%. Mean estimated compressive loads delivered to the
      tibia were approximately 1-1.5 times body weight. The training protocol yielded
      significant trained versus untrained limb differences for torque (+24%), torque
      time integral (+27%), fatigue index (+50%), torque rise time (+45%), and between
      twitch fusion (+15%). These between-limb differences were even greater when
      measured at the end of a repetitive stimulation protocol (125 contractions).
      Peripheral quantitative computed tomography revealed 31% higher distal tibia
      trabecular BMD in trained limbs than in untrained limbs. The intervention used in
      this study was sufficient to limit many of the deleterious muscular and skeletal
      adaptations that normally occur after SCI. Importantly, this method of load
      delivery was feasible and may serve as the basis for an intervention to preserve
      the musculoskeletal properties of individuals with SCI.

PMID- 16407427
TI  - Brain-derived neurotrophic factor silences GABA synapses onto hypothalamic
      neuroendocrine cells through a postsynaptic dynamin-mediated mechanism.
AB  - In the paraventricular nucleus of the hypothalamus (PVN), experimental stress
      paradigms that suppress gamma-aminobutyric acid (GABA) inputs to parvocellular
      neuroendocrine cells (PNCs) also increase the expression of brain-derived
      neurotrophic factor (BDNF). In the adult CNS, BDNF regulates the efficacy of
      GABAergic transmission, but its contributions to functional changes at inhibitory
      synapses in the PVN have not been investigated. Analysis of quantal transmission
      revealed a decrease in the frequency of miniature inhibitory postsynaptic
      currents (mIPSCs) in response to BDNF with no accompanying changes in their
      amplitude. These effects were completely blocked by prior inclusion of the TrKB
      receptor antagonist K252a in the patch pipette. Inclusion of a dynamin inhibitory
      peptide in the patch pipette also blocked the effects of BDNF, consistent with an
      all-or-none removal of clusters of postsynaptic GABAA receptors. Finally, to
      confirm a decrease in the availability of postsynaptic GABAA receptors, we tested
      the effects of BDNF on focal application of the GABAA agonist muscimol.
      Postsynaptic responses to muscimol were reduced after BDNF. Collectively, these
      data indicate that BDNF remodels functional synaptic contacts putatively by
      reducing the surface expression of postsynaptic GABAA receptors.

PMID- 16407428
TI  - Neural correlates of the dependence of compensatory eye movements during
      translation on target distance and eccentricity.
AB  - To stabilize objects of interest on the fovea during translation, vestibular
      driven compensatory eye movements [translational vestibulo-ocular reflex (TVOR)]
      must scale with both target distance and eccentricity. To identify the neural
      correlates of these properties, we recorded from different groups of eye movement
      sensitive neurons in the prepositus hypoglossi and vestibular nuclei of macaque
      monkeys during lateral and fore-aft displacements. All neuron types exhibited
      some increase in modulation amplitude as a function of target distance during
      high-frequency (4 Hz) lateral motion in darkness, with slopes that were
      correlated with the cell's pursuit gain, but not eye position sensitivity.
      Vergence angle dependence was largest for burst-tonic (BT) and contralateral eye
      head (EH) neurons and smallest for ipsilateral EH and position-vestibular-pause
      (PVP) cells. On the other hand, the EH and PVP neurons with ipsilateral eye
      movement preferences exhibited the largest vergence-independent responses, which
      would be inappropriate to drive the TVOR. In addition to target distance, the
      TVOR also scales with target eccentricity, as evidenced during fore-aft motion,
      where eye velocity amplitude exhibits a "V-shaped " dependence and phase shifts
      180 degrees for right versus left eye positions. Both the modulation amplitude
      and phase of BT and contralateral EH cells scaled with eye position, similar to
      the evoked eye movements during fore-aft motion. In contrast, the response
      modulation of ipsilateral EH and PVP cells during fore-aft motion was
      characterized by neither the V-shaped scaling nor the phase reversal. These
      results show that distinct premotor cell types carry neural signals that are
      appropriately scaled by vergence angle and eye position to generate the
      geometrically appropriate compensatory eye movements in the translational
      vestibulo-ocular reflex.

PMID- 16407429
TI  - Activity of tonically active neurons in the monkey putamen during initiation and
      withholding of movement.
AB  - Tonically active neurons (TANs) of the primate striatum are putative interneurons
      that respond to events of motivational significance, such as primary rewards, and
      to sensory stimuli that predict such events. Because TANs influence striatal
      projection neurons, TANs may play a role in the initiation and control of
      movement. To examine this issue, we recorded from putaminal TANs in macaque
      monkeys trained to make the same arm movement in two ways--in reaction to an
      external cue and also after a variable delay without an explicit instruction to
      move (self-timed movements). On other trials, the animals had to withhold
      movement following an external cue. The task design ensured that the three types
      of trials were effectively randomly interleaved, equally frequent, and similar in
      overall timing. Separately, we presented "playback" trials in which the same
      sequence of visual stimulation and reward was presented while the animals fixated
      without making the arm movement. We found that TAN responses were strongly
      affected by behavioral context. In particular, TAN responses were strikingly
      stronger when the animals actively withheld movements than on the corresponding
      playback trials, even though the stimulus sequence and reward timing were
      identical and no movement was made in either case. Many TANs also became active
      in the absence of a proximate sensory cue on self-timed movements, suggesting
      that TANs may reflect internal processes that are specific to self-timed
      movements. These results suggest that TANs may directly participate in, or
      monitor the motivational significance of, an animal's actions as well as external
      events.

PMID- 16407430
TI  - Inhibitory synaptic transmission differs in mouse type A and B medial vestibular
      nucleus neurons in vitro.
AB  - Fast inhibitory synaptic transmission in the medial vestibular nucleus (MVN) is
      mediated by GABA(A) receptors (GABA(A)Rs) and glycine receptors (GlyRs). To
      assess their relative contribution to inhibition in the MVN, we recorded
      miniature inhibitory postsynaptic currents (mIPSCs) in physiologically
      characterized type A and type B MVN neurons. Transverse brain stem slices were
      prepared from mice (3-8 wk old), and whole cell patch-clamp recordings were
      obtained from visualized MVN neurons (CsCl internal; Vm = -70 mV; 23 degrees C).
      In 81 MVN neurons, 69% received exclusively GABA(A)ergic inputs, 6% exclusively
      glycinergic inputs, and 25% received both types of mIPSCs. The mean amplitude of
      GABA(A)R-mediated mIPSCs was smaller than those mediated by GlyRs (22.6 +/- 1.8
      vs. 35.3 +/- 5.3 pA). The rise time and decay time constants of GABA(A)R- versus
      GlyR-mediated mIPSCs were slower (1.3 +/- 0.1 vs. 0.9 +/- 0.1 ms and 10.5 +/- 0.3
      vs. 4.7 +/- 0.3 ms, respectively). Comparison of type A (n = 20) and type B (n =
      32) neurons showed that type A neurons received almost exclusively GABA(A)ergic
      inhibitory inputs, whereas type B neurons received GABA(A)ergic inputs,
      glycinergic inputs, or both. Intracellular labeling in a subset of MVN neurons
      showed that morphology was not related to a MVN neuron's inhibitory profile (n =
      15), or whether it was classified as type A or B (n = 29). Together, these
      findings indicate that both GABA and glycine contribute to inhibitory synaptic
      processing in MVN neurons, although GABA dominates and there is a difference in
      the distribution of GABA(A) and Gly receptors between type A and type B MVN
      neurons.

PMID- 16407431
TI  - Proton sensitivity Ca2+ permeability and molecular basis of acid-sensing ion
      channels expressed in glabrous and hairy skin afferents.
AB  - We contrasted the physiology and peripheral targets of subclassified nociceptive
      and nonnociceptive afferents that express acid-sensing ion channel (ASIC)-like
      currents. The threshold for current activation was similar in eight distinct cell
      subclasses regardless of functional modality (pH 6.8). When potency was
      determined from concentration-response curves, nonnociceptors exhibited currents
      with significantly greater potency than that of all but one class of nociceptors
      (pH50 = 6.54 and 6.75 vs. 6.20-6.34). In nonnociceptive cells, acid transduction
      was also confined to a very narrow range (0.1-0.3 vs. 0.8-1.4 pH units for
      nociceptors). Simultaneous whole cell recording and ratiometric imaging of three
      peptidergic nociceptive classes were consistent with the expression of Ca2+ 
      permeable ASICs. Sensitivity to psalmotoxin and flurbiprofen indicated the
      presence of Ca2+ -permeable ASIC1a. Immunocytochemistry on these subclassified
      populations revealed a differential distribution of five ASIC proteins consistent
      with Ca2+ permeability and differential kinetics of proton-gated currents (type
      5: ASIC1a, 1b, 2a, 2b, 3; type 8a: ASIC1a, 1b, 3; type 8b: ASIC1a, 1b, 2a, 2b,
      3). Using DiI tracing, we found that nociceptive classes had discrete peripheral
      targets. ASIC-expressing types 8a and 9 projected to hairy skin, but only types
      8a and 13 projected to glabrous skin. Non-ASIC-expressing types 2 and 4 were
      present only in hairy skin. We conclude that ASIC-expressing nociceptors differ
      from ASIC-expressing nonnociceptors mainly by range of proton reactivity. ASIC-
      as well as non-ASIC-expressing nociceptors have highly distinct cutaneous
      targets, and only one class was consistent with the existence of a generic C
      polymodal nociceptor (type 8a).

PMID- 16407432
TI  - Local shuffling of spike trains boosts the accuracy of spike train spectral
      analysis.
AB  - Spectral analysis of neuronal spike trains is an important tool in understanding
      the characteristics of neuronal activity by providing insights into normal and
      pathological periodic oscillatory phenomena. However, the refractory period
      creates high-frequency modulations in spike-train firing rate because any rise in
      the discharge rate causes a descent in subsequent time bins, leading to
      multifaceted modifications in the structure of the spectrum. Thus the power
      spectrum of the spiking activity (autospectrum) displays elevated energy in high
      frequencies relative to the lower frequencies. The spectral distortion is more
      dominant in neurons with high firing rates and long refractory periods and can
      lead to reduced identification of low-frequency oscillations (such as the 5- to
      10-Hz burst oscillations typical of Parkinsonian basal ganglia and thalamus). We
      propose a compensation process that uses shuffling of interspike intervals (ISIs)
      for reliable identification of oscillations in the entire frequency range. This
      compensation is further improved by local shuffling, which preserves the slow
      changes in the discharge rate that may be lost in global shuffling. Cross-spectra
      of pairs of neurons are similarly distorted regardless of their correlation
      level. Consequently, identification of low-frequency synchronous oscillations,
      even for two neurons recorded by a single electrode, is improved by ISI
      shuffling. The ISI local shuffling is computed with confidence limits that are
      based on the first-order statistics of the spike trains, thus providing a
      reliable estimation of auto- and cross-spectra of spike trains and making it an
      optimal tool for physiological studies of oscillatory neuronal phenomena.

PMID- 16407433
TI  - Influence of environmental factors on facial ageing.
AB  - BACKGROUND: A recent twin study has shown that 'looking old for one's age' is
      associated with increased mortality. Approximately 40% of the variation in
      perceived age is due to non-genetic factors. OBJECTIVE: To examine environmental
      factors influencing perceived age controlling for diseases. DESIGN: A twin study.
      SETTING: In the 2001 wave of the population-based survey--the Longitudinal Study
      of Aging Danish Twins--participants provided information on a wide range of
      exposures and health indicators. Additionally, they were asked to have a face
      photograph taken. SUBJECTS: A total of 1826 elderly (70+) twins who had a high
      quality face photograph taken. METHODS: Ten nurses assessed the visual age of
      each twin from the face photograph. The mean of the nurses' age estimates for
      each twin was used as the twin's perceived age. Multivariate linear regression
      and intrapair comparison (for intact twin pairs) were used for analyses. RESULTS:
      Statistically significant determinants of facial ageing associated with high
      perceived age for men were smoking (P = 0.01), sun exposure (P = 0.02) and low
      body mass index (BMI) (P<0.005), while for women they were low BMI (P = 0.05) and
      low social class (P<0.005). The number of children (men) and marital status (P =
      0.08) and depression symptomatology score (women) were borderline significantly
      associated with facial ageing. CONCLUSION: Our study confirms previous findings
      of a negative influence of sun exposure, smoking and a low BMI on facial ageing.
      Furthermore, our study indicates that high social status, low depression score
      and being married are associated with a younger look, but the strength of the
      associations varies between genders.

PMID- 16407434
TI  - Differences in care received by patients with and without dementia who died
      during acute hospital admission: a retrospective case note study.

PMID- 16407435
TI  - Acute Epstein-Barr virus infection in two elderly individuals.
AB  - Most individuals acquire Epstein-Barr virus (EBV) infection in young age. Because
      of uncommon presentation and misdiagnosis, clinical manifestations are less well
      described in older age. We present two cases of elderly patients with predominant
      symptoms attributed to cold agglutinin haemolytic anaemia due to acute EBV
      infection without fever, lymphadenopathy, pharyngitis or splenomegaly. We
      conclude that misleading clinical manifestations are frequent in older
      individuals and may lead to inappropriate diagnostic invasive procedures.

PMID- 16407436
TI  - Are restrained children under 15 years of age in cars as effectively protected as
      adults?
AB  - AIM: To compare the injury distribution between children and adults, injured as
      restrained car passengers. METHODS: Population based study of data from a French
      road trauma registry in 1996-2002. Children under 15 years old were compared with
      adult casualties according to the distribution of serious injuries in three
      distinct body regions (head, chest, and abdomen) when they were restrained car
      passengers. A multivariate logistic regression was performed to quantify the risk
      of AIS2+ injury (Abbreviated Injury Scale of 2 or more). RESULTS: Among the 7568
      casualties who were injured as restrained car passengers in car accidents, 1033
      were less than 15 years old. Overall, 35.4% of children and 25.2% of adults were
      unrestrained. For children and adults, the risk of fatality was significantly
      reduced when they were restrained, but the percentages of children with Injury
      Severity Score (ISS) > or =16, were not significantly different between
      restrained and not restrained casualties. Compared to adults, restrained children
      aged 5-9 were 2.7 times (OR 2.74; 95% CI 1.17 to 6.43) as likely to sustain an
      AIS2+ abdominal injury, and tended to be more at risk of AIS2+ head injuries, but
      were less at risk of AIS2+ chest injuries. CONCLUSIONS: Children aged 5-9 years
      injured in road accidents as restrained car passengers were more likely to
      sustain an AIS2+ abdominal injury than adults. This emphasises the need to
      reinforce educational campaigns aimed not only at getting children into restraint
      systems, but also insisting on their correct use.

PMID- 16407437
TI  - Abscisic acid stimulates a calcium-dependent protein kinase in grape berry.
AB  - It has been demonstrated that calcium plays a central role in mediating abscisic
      acid (ABA) signaling, but many of the Ca2+-binding sensory proteins as the
      components of the ABA-signaling pathway remain to be elucidated. Here we
      identified, characterized, and purified a 58-kD ABA-stimulated calcium-dependent
      protein kinase from the mesocarp of grape berries (Vitis vinifera x Vitis
      labrusca), designated ACPK1 (for ABA-stimulated calcium-dependent protein
      kinase1). ABA stimulates ACPK1 in a dose-dependent manner, and the ACPK1
      expression and enzyme activities alter accordantly with the endogenous ABA
      concentrations during fruit development. The ABA-induced ACPK1 stimulation
      appears to be transient with a rapid effect in 15 min but also with a slow and
      steady state of induction after 60 min. ABA acts on ACPK1 indirectly and
      dependently on in vivo state of the tissues. Two inactive ABA isomers, (-)-2-cis,
      4-trans-ABA and 2-trans, 4-trans-(+/-)-ABA, are ineffective for inducing ACPK1
      stimulation, revealing that the ABA-induced effect is stereo specific to
      physiological active (+)-2-cis, 4-trans-ABA. The other phytohormones such as
      auxin indoleacetic acid, gibberellic acid, synthetic cytokinin N-benzyl-6
      aminopurine, and brassinolide are also ineffective in this ACPK1 stimulation.
      Based on sequencing of the two-dimensional electrophoresis-purified ACPK1, we
      cloned the ACPK1 gene. The ACPK1 is expressed specifically in grape berry
      covering a fleshy portion and seeds, and in a developmental stage-dependent
      manner. We further showed that ACPK1 is localized in both plasma membranes and
      chloroplasts/plastids and positively regulates plasma membrane H+-ATPase in
      vitro, suggesting that ACPK1 may be involved in the ABA-signaling pathway.

PMID- 16407438
TI  - Rewiring mitogen-activated protein kinase cascade by positive feedback confers
      potato blight resistance.
AB  - Late blight, caused by the notorious pathogen Phytophthora infestans, is a
      devastating disease of potato (Solanum tuberosum) and tomato (Solanum
      lycopersicum), and during the 1840s caused the Irish potato famine and over one
      million fatalities. Currently, grown potato cultivars lack adequate blight
      tolerance. Earlier cultivars bred for resistance used disease resistance genes
      that confer immunity only to some strains of the pathogen harboring corresponding
      avirulence gene. Specific resistance gene-mediated immunity and chemical controls
      are rapidly overcome in the field when new pathogen races arise through mutation,
      recombination, or migration from elsewhere. A mitogen-activated protein kinase
      (MAPK) cascade plays a pivotal role in plant innate immunity. Here we show that
      the transgenic potato plants that carry a constitutively active form of MAPK
      kinase driven by a pathogen-inducible promoter of potato showed high resistance
      to early blight pathogen Alternaria solani as well as P. infestans. The pathogen
      attack provoked defense-related MAPK activation followed by induction of NADPH
      oxidase gene expression, which is implicated in reactive oxygen species
      production, and resulted in hypersensitive response-like phenotype. We propose
      that enhancing disease resistance through altered regulation of plant defense
      mechanisms should be more durable and publicly acceptable than engineering
      overexpression of antimicrobial proteins.

PMID- 16407439
TI  - A novel plant-specific family gene, ROOT PRIMORDIUM DEFECTIVE 1, is required for
      the maintenance of active cell proliferation.
AB  - Hypocotyl segments of Arabidopsis (Arabidopsis thaliana) produce adventitious
      roots in response to exogenously supplied auxin. root primordium defective 1
      (rpd1) is a temperature-sensitive mutant isolated on the basis of impairment in
      this phenomenon. This study describes further phenotypic analysis of the rpd1
      mutant and isolation of the RPD1 gene. When adventitious root formation was
      induced from the rpd1 explants at the restrictive temperature, cell proliferation
      leading to root promordia formation was initiated at the same time as in wild
      type explants. However, development of the root primordia was arrested thereafter
      in the mutant. Temperature-shift experiments indicated that RPD1 exerts its
      function before any visible sign of root primordium formation. The expression
      patterns of the auxin-responsive gene DR5:beta-glucuronidase and the
      cytodifferentiation marker gene SCARECROW suggest that the rpd1 mutation
      interferes with neither axis formation nor cellular patterning at the initial
      stage of root primordium development. Taken together with the effect of the rpd1
      mutation on callus cell proliferation, these data imply a role for RPD1 in
      prearranging the maintenance of the active cell proliferation during root
      primordium development. Positional cloning of the RPD1 gene revealed that it
      encodes a member of a novel protein family specific to the plant kingdom.
      Disruption of the RPD1 gene by a T-DNA insertion caused embryogenesis arrest at
      the globular to transition stages. This phenotype is consistent with the
      hypothesized function of RPD1 in the maintenance of active cell proliferation.

PMID- 16407440
TI  - The fertilization-induced DNA replication factor MCM6 of maize shuttles between
      cytoplasm and nucleus, and is essential for plant growth and development.
AB  - The eukaryotic genome is duplicated exactly once per cell division cycle. A
      strategy that limits every replication origin to a single initiation event is
      tightly regulated by a multiprotein complex, which involves at least 20 protein
      factors. A key player in this regulation is the evolutionary conserved hexameric
      MCM2-7 complex. From maize (Zea mays) zygotes, we have cloned MCM6 and
      characterized this essential gene in more detail. Shortly after fertilization,
      expression of ZmMCM6 is strongly induced. During progression of zygote and
      proembryo development, ZmMCM6 transcript amounts decrease and are low in
      vegetative tissues, where expression is restricted to tissues containing
      proliferating cells. The highest protein amounts are detectable about 6 to 20 d
      after fertilization in developing kernels. Subcellular localization studies
      revealed that MCM6 protein shuttles between cytoplasm and nucleoplasm in a cell
      cycle-dependent manner. ZmMCM6 is taken up by the nucleus during G1 phase and the
      highest protein levels were observed during late G1/S phase. ZmMCM6 is excluded
      from the nucleus during late S, G2, and mitosis. Transgenic maize was generated
      to overexpress and down-regulate ZmMCM6. Plants displaying minor antisense
      transcript amounts were reduced in size and did not develop cobs to maturity.
      Down-regulation of ZmMCM6 gene activity seems also to affect pollen development
      because antisense transgenes could not be propagated via pollen to wild-type
      plants. In summary, the transgenic data indicate that MCM6 is essential for both
      vegetative as well as reproductive growth and development in plants.

PMID- 16407441
TI  - Photosynthesis, productivity, and yield of maize are not affected by open-air
      elevation of CO2 concentration in the absence of drought.
AB  - While increasing temperatures and altered soil moisture arising from climate
      change in the next 50 years are projected to decrease yield of food crops,
      elevated CO2 concentration ([CO2]) is predicted to enhance yield and offset these
      detrimental factors. However, C4 photosynthesis is usually saturated at current
      [CO2] and theoretically should not be stimulated under elevated [CO2].
      Nevertheless, some controlled environment studies have reported direct
      stimulation of C4 photosynthesis and productivity, as well as physiological
      acclimation, under elevated [CO2]. To test if these effects occur in the open air
      and within the Corn Belt, maize (Zea mays) was grown in ambient [CO2] (376
      micromol mol(-1)) and elevated [CO2] (550 micromol mol(-1)) using Free-Air
      Concentration Enrichment technology. The 2004 season had ideal growing conditions
      in which the crop did not experience water stress. In the absence of water
      stress, growth at elevated [CO2] did not stimulate photosynthesis, biomass, or
      yield. Nor was there any CO2 effect on the activity of key photosynthetic
      enzymes, or metabolic markers of carbon and nitrogen status. Stomatal conductance
      was lower (-34%) and soil moisture was higher (up to 31%), consistent with
      reduced crop water use. The results provide unique field evidence that
      photosynthesis and production of maize may be unaffected by rising [CO2] in the
      absence of drought. This suggests that rising [CO2] may not provide the full
      dividend to North American maize production anticipated in projections of future
      global food supply.

PMID- 16407442
TI  - Exposed loop domains of complexed 14-3-3 proteins contribute to structural
      diversity and functional specificity.
AB  - The 14-3-3 family of proteins functions through protein:phosphoprotein
      interactions, the nature of which has been elucidated using x-ray
      crystallography. However, some key structural features in nonconserved regions
      have yet to be fully resolved, leaving open questions regarding the functional
      selectivity of 14-3-3 family members for diverse clients. In an effort to study
      surface accessible structural features in 14-3-3 containing macromolecular
      complexes and to illuminate important structure/function variations among the 14
      3-3 isoforms, we determined the epitopes for three unique monoclonal antibodies
      (mAbs) developed against the Arabidopsis (Arabidopsis thaliana) G-box DNA:protein
      complex. The epitopes mapped to different loops in a phylogenetically important
      subset of the 13 14-3-3 family members. All three epitopes were on a common
      exposed face of complexed 14-3-3s. Two of the mAbs recognized linear sequences
      within loops 5 and 6, while the third mAb recognized 14-3-3 residues surrounding
      the pivotal medial Gly in the divalent cation-binding domain of loop 8, together
      with distal residue(s) in the putative dynamic 10th helix that has yet to be
      determined by crystallography. Gly at this loop 8 position is unique to
      nonepsilon 14-3-3 isoforms of the plant kingdom, suggesting that this region
      constitutes a plant-specific key functional 14-3-3 feature and highlighting that
      the loop 8 region is functionally significant. Mutagenesis of the medial amino
      acid in the loop 8 domain changed the flexibility of the C terminus and altered
      client peptide-binding selectivity, demonstrating the functional significance of
      the surface accessible, evolutionarily distinct loop 8 domain.

PMID- 16407443
TI  - Molecular characterization and phylogeny of U2AF35 homologs in plants.
AB  - U2AF (U2 small nuclear ribonucleoprotein auxiliary factor) is an essential
      splicing factor with critical roles in recognition of the 3'-splice site. In
      animals, the U2AF small subunit (U2AF35) can bind to the 3'-AG intron border and
      promote U2 small nuclear RNP binding to the branch-point sequences of introns
      through interaction with the U2AF large subunit. Two copies of U2AF35-encoding
      genes were identified in Arabidopsis (Arabidopsis thaliana; atU2AF35a and
      atU2AF35b). Both are expressed in all tissues inspected, with atU2AF35a expressed
      at a higher level than atU2AF35b in most tissues. Differences in the expression
      patterns of atU2AF35a and atU2AF35b in roots were revealed by a promoter::beta
      glucuronidase assay, with atU2AF35b expressed strongly in whole young roots and
      root tips and atU2AF35a limited to root vascular regions. Altered expression
      levels of atU2AF35a or atU2AF35b cause pleiotropic phenotypes (including
      flowering time, leaf morphology, and flower and silique shape). Novel slicing
      isoforms were generated from FCA pre-mRNA by splicing of noncanonical introns in
      plants with altered expression levels of atU2AF35. U2AF35 homologs were also
      identified from maize (Zea mays) and other plants with large-scale expressed
      sequence tag projects. A C-terminal motif (named SERE) is highly conserved in all
      seed plant protein homologs, suggesting it may have an important function
      specific to higher plants.

PMID- 16407444
TI  - Genome-wide analysis of the ERF gene family in Arabidopsis and rice.
AB  - Genes in the ERF family encode transcriptional regulators with a variety of
      functions involved in the developmental and physiological processes in plants. In
      this study, a comprehensive computational analysis identified 122 and 139 ERF
      family genes in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa L.
      subsp. japonica), respectively. A complete overview of this gene family in
      Arabidopsis is presented, including the gene structures, phylogeny, chromosome
      locations, and conserved motifs. In addition, a comparative analysis between
      these genes in Arabidopsis and rice was performed. As a result of these analyses,
      the ERF families in Arabidopsis and rice were divided into 12 and 15 groups,
      respectively, and several of these groups were further divided into subgroups.
      Based on the observation that 11 of these groups were present in both Arabidopsis
      and rice, it was concluded that the major functional diversification within the
      ERF family predated the monocot/dicot divergence. In contrast, some
      groups/subgroups are species specific. We discuss the relationship between the
      structure and function of the ERF family proteins based on these results and
      published information. It was further concluded that the expansion of the ERF
      family in plants might have been due to chromosomal/segmental duplication and
      tandem duplication, as well as more ancient transposition and homing. These
      results will be useful for future functional analyses of the ERF family genes.

PMID- 16407446
TI  - Evidence for functional conservation, sufficiency, and proteolytic processing of
      the CLAVATA3 CLE domain.
AB  - Arabidopsis (Arabidopsis thaliana) CLAVATA3 (CLV3) is hypothesized to act as a
      ligand for the CLV1 receptor kinase in the regulation of stem cell specification
      at shoot and flower meristems. CLV3 is a secreted protein, with an amino-terminal
      signal sequence and a conserved C-terminal domain of 15 amino acids, termed the
      CLE (CLV3/ESR-related) domain, based on its similarity to a largely unstudied
      protein family broadly present in land plants. We have tested the function of 13
      Arabidopsis CLEs in vivo and found a significant variability in the ability of
      CLEs to replace CLV3, ranging from complete to no complementation. The best
      rescuing CLE depends on CLV1 for function, while other CLEs act independently of
      CLV1. Domain-swap experiments indicate that differences in function can be traced
      to the CLE domain within these proteins. Indeed, when the CLE domain of CLV3 is
      placed downstream of an unrelated signal sequence, it is capable of fully
      replacing CLV3 function. Finally, we have detected proteolytic activity in
      extracts from cauliflower (Brassica oleracea) that process both CLV3 and CLE1 at
      their C termini. For CLV3, processing appears to occur at the absolutely
      conserved arginine-70 found at the beginning of the CLE domain. We propose that
      CLV3 and other CLEs are C-terminally processed to generate an active CLE peptide.

PMID- 16407445
TI  - Evidence for involvement of photosynthetic processes in the stomatal response to
      CO2.
AB  - Stomatal conductance (gs) typically declines in response to increasing
      intercellular CO2 concentration (ci). However, the mechanisms underlying this
      response are not fully understood. Recent work suggests that stomatal responses
      to ci and red light (RL) are linked to photosynthetic electron transport. We
      investigated the role of photosynthetic electron transport in the stomatal
      response to ci in intact leaves of cocklebur (Xanthium strumarium) plants by
      examining the responses of gs and net CO2 assimilation rate to ci in light and
      darkness, in the presence and absence of the photosystem II inhibitor 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU), and at 2% and 21% ambient oxygen. Our
      results indicate that (1) gs and assimilation rate decline concurrently and with
      similar spatial patterns in response to DCMU; (2) the response of gs to ci
      changes slope in concert with the transition from Rubisco- to electron transport
      limited photosynthesis at various irradiances and oxygen concentrations; (3) the
      response of gs to ci is similar in darkness and in DCMU-treated leaves, whereas
      the response in light in non-DCMU-treated leaves is much larger and has a
      different shape; (4) the response of gs to ci is insensitive to oxygen in DCMU
      treated leaves or in darkness; and (5) stomata respond normally to RL when ci is
      held constant, indicating the RL response does not require a reduction in ci by
      mesophyll photosynthesis. Together, these results suggest that part of the
      stomatal response to ci involves the balance between photosynthetic electron
      transport and carbon reduction either in the mesophyll or in guard cell
      chloroplasts.

PMID- 16407447
TI  - The role of OsBRI1 and its homologous genes, OsBRL1 and OsBRL3, in rice.
AB  - Since first identifying two alleles of a rice (Oryza sativa) brassinosteroid (BR)
      insensitive mutant, d61, that were also defective in an orthologous gene in
      Arabidopsis (Arabidopsis thaliana) BRASSINOSTEROID INSENSITIVE1 (BRI1), we have
      isolated eight additional alleles, including null mutations, of the rice BRI1
      gene OsBRI1. The most severe mutant, d61-4, exhibited severe dwarfism and twisted
      leaves, although pattern formation and differentiation were normal. This severe
      shoot phenotype was caused mainly by a defect in cell elongation and the
      disturbance of cell division after the determination of cell fate. In contrast to
      its severe shoot phenotype, the d61-4 mutant had a mild root phenotype.
      Concomitantly, the accumulation of castasterone, the active BR in rice, was up to
      30-fold greater in the shoots, while only 1.5-fold greater in the roots. The
      homologous genes for OsBRI1, OsBRL1 and OsBRL3, were highly expressed in roots
      but weakly expressed in shoots, and their expression was higher in d61-4 than in
      the wild type. Based on these observations, we conclude that OsBRI1 is not
      essential for pattern formation or organ initiation, but is involved in organ
      development through controlling cell division and elongation. In addition, OsBRL1
      and OsBRL3 are at least partly involved in BR perception in the roots.

PMID- 16407449
TI  - Nitrogen fixation mutants of Medicago truncatula fail to support plant and
      bacterial symbiotic gene expression.
AB  - The Rhizobium-legume symbiosis culminates in the exchange of nutrients in the
      root nodule. Bacteria within the nodule reduce molecular nitrogen for plant use
      and plants provide bacteria with carbon-containing compounds. Following the
      initial signaling events that lead to plant infection, little is known about the
      plant requirements for establishment and maintenance of the symbiosis. We
      screened 44,000 M2 plants from fast neutron-irradiated Medicago truncatula seeds
      and isolated eight independent mutant lines that are defective in nitrogen
      fixation. The eight mutants are monogenic and represent seven complementation
      groups. To monitor bacterial status in mutant nodules, we assayed Sinorhizobium
      meliloti symbiosis gene promoters (nodF, exoY, bacA, and nifH) in the defective
      in nitrogen fixation mutants. Additionally, we used an Affymetrix oligonucleotide
      microarray to monitor gene expression changes in wild-type and three mutant
      plants during the nodulation process. These analyses suggest the mutants can be
      separated into three classes: one class that supports little to no nitrogen
      fixation and minimal bacterial expression of nifH; another class that supports no
      nitrogen fixation and minimal bacterial expression of nodF, bacA, and nifH; and a
      final class that supports low levels of both nitrogen fixation and bacterial nifH
      expression.

PMID- 16407448
TI  - Mitosis-specific promoter of the alfalfa cyclin-dependent kinase gene
      (Medsa;CDKB2;1) is activated by wounding and ethylene in a non-cell division
      dependent manner.
AB  - Cyclin-dependent serine/threonine kinases (CDKs) have pivotal roles in regulating
      the eukaryotic cell cycle. Plants possess a unique class of CDKs (B-type CDKs)
      with preferential protein accumulation at G2/M-phases; however, their exact
      functions are still enigmatic. Here we describe the functional characterization
      of a 360-bp promoter region of the alfalfa (Medicago sativa) CDKB2;1 gene in
      transgenic plants and cell lines. It is shown that the activity of the analyzed
      promoter was characteristic for proliferating meristematic regions in planta and
      specific for cells in the G2/M-phases in synchronized cell cultures.
      Immunohistochemical analysis of transgenic root sections further confirmed the
      correlation of the expression of the CDKB2;1 promoter-linked reporter genes with
      the accumulation of the correspondent kinase. It was found that, in addition to
      auxin (2,4-dichlorophenoxyacetic acid) treatment, wounding could also induce both
      the reporter and endogenous genes in transgenic leaf explants. Furthermore,
      ethylene, known as a wound-response mediator, had a similar effect. The gene
      activation in response to wounding or ethephon was faster and occurred without
      the induction of cell cycle progression in contrast to the control auxin
      treatment. In silico analysis of this promoter indeed revealed the presence of a
      set of cis-elements, indicating not only cell cycle- but wound- and ethylene
      dependent regulation of this CDK gene. Based on the presented data, we discuss
      the functional significance of the complex regulation of mitosis-specific CDK
      genes in plants.

PMID- 16407450
TI  - Glutamine synthetase-glutamate synthase pathway and glutamate dehydrogenase play
      distinct roles in the sink-source nitrogen cycle in tobacco.
AB  - Glutamate (Glu) metabolism and amino acid translocation were investigated in the
      young and old leaves of tobacco (Nicotiana tabacum L. cv Xanthi) using
      [15N]ammonium and [2-15N]Glu tracers. Regardless of leaf age, [15N]ammonium
      assimilation occurred via glutamine synthetase (GS; EC 6.1.1.3) and Glu synthase
      (ferredoxin [Fd]-GOGAT; EC 1.4.7.1; NADH-GOGAT; EC 1.4.1.14), both in the light
      and darkness, and it did not depend on Glu dehydrogenase (GDH; EC 1.4.1.2). The
      [15N]ammonium and ammonium accumulation patterns support the role of GDH in the
      deamination of [2-15N]Glu to provide 2-oxoglutarate and [15N]ammonium. In the
      dark, excess [15N]ammonium was incorporated into asparagine that served as an
      additional detoxification molecule. The constant Glu levels in the phloem sap
      suggested that Glu was continuously synthesized and supplied into the phloem
      regardless of leaf age. Further study using transgenic tobacco lines, harboring
      the promoter of the GLU1 gene (encoding Arabidopsis [Arabidopsis thaliana] Fd
      GOGAT) fused to a GUS reporter gene, revealed that the expression of Fd-GOGAT
      remained higher in young leaves compared to old leaves, and higher in the veins
      compared to the mesophyll. Confocal laser-scanning microscopy localized the Fd
      GOGAT protein to the phloem companion cells-sieve element complex in the leaf
      veins. The results are consistent with a role of Fd-GOGAT in supplying Glu for
      the synthesis and transport of amino acids. Taken together, the data provide
      evidence that the GS-GOGAT pathway and GDH play distinct roles in the source-sink
      nitrogen cycle of tobacco leaves.

PMID- 16407451
TI  - The regulation of DWARF4 expression is likely a critical mechanism in maintaining
      the homeostasis of bioactive brassinosteroids in Arabidopsis.
AB  - Mutants that are defective in brassinosteroid (BR) biosynthesis or signaling
      display severely retarded growth patterns due to absence of growth-promoting
      effects by BRs. Arabidopsis (Arabidopsis thaliana) DWARF4 (DWF4) catalyzes a flux
      determining step in the BR biosynthetic pathways. Thus, it is hypothesized that
      the tissues of DWF4 expression may represent the sites of BR biosynthesis in
      Arabidopsis. Here we show that DWF4 transcripts accumulate in the actively
      growing tissues, such as root, shoot apices with floral clusters, joint tissues
      of root and shoot, and dark-grown seedlings. Conforming to the RNA gel-blot
      analysis, DWF4:beta-glucuronidase (GUS) histochemical analyses more precisely
      define the tissues that express the DWF4 gene. Examination of the endogenous
      levels of BRs in six and seven different tissues of wild type and brassinosteroid
      insensitive1-5 mutant, respectively, revealed that BRs are significantly enriched
      in roots, shoot tips, and joint tissues of roots and shoots. In addition,
      DWF4:GUS expression was negatively regulated by BRs. DWF4:GUS activity was
      increased by treatment with brassinazole, a BR biosynthetic inhibitor, and
      decreased by exogenous application of bioactive BRs. When DWF4:GUS was expressed
      in a different genetic background, its level was down-regulated in brassinazole
      resistant1-D, confirming that BRASSINAZOLE RESISTANT1 acts as a negative
      regulator of DWF4. Interestingly, in the brassinosteroid insensitive2/dwf12-1D
      background, DWF4:GUS expression was intensified and delocalized to elongating
      zones of root, suggesting that BRASSINOSTEROID INSENSITIVE2 is an important
      factor that limits DWF4 expression. Thus, it is likely that the DWF4 promoter
      serves as a focal point in maintaining homeostasis of endogenous bioactive BR
      pools in specific tissues of Arabidopsis.

PMID- 16407452
TI  - Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non
      obese adolescents and women.
AB  - Polycystic ovary syndrome (PCOS) is a variable disorder that is characterized in
      adolescents and young women by a broad spectrum of anomalies, including
      hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity and low-grade
      inflammation. At present, there is no approved therapy for PCOS. Recent studies
      indicate that a low-dose combination of flutamide (Flu; a generic androgen
      receptor blocker) and metformin (Met; a generic insulin-sensitizer) normalizes
      the adolescent PCOS spectrum more than an oral contraceptive (OC); in young
      women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met than
      by OC alone. Within the pathophysiological cascade of PCOS, Flu-Met seems to
      counter upstream anomalies like hyperinsulinemia or hyperandrogenism, thereby
      preventing or reversing downstream effects. In contrast, an OC essentially masks
      downstream symptoms like hirsutism, acne or irregular menses, whereas the
      upstream aberrations remain unaltered or may even be worsened. The available
      experience with Flu-Met is limited but promising. We emphasize that Flu-Met may
      (as part of its efficacy) induce ovulation but is contra-indicated post
      conception because of potential embryotoxicity; therefore, it seems wise to
      combine Flu-Met with an oral or a transdermal oestro-progestagen or with a non
      endocrine method of contraception. May this update prompt further research into
      Flu-Met's therapeutic potential in patients with PCOS. Until the abovementioned
      effects have been broadly confirmed, Flu-Met should not be regarded as a standard
      therapy for widespread clinical practice.

PMID- 16407453
TI  - Glycolysis and sperm motility: does a spoonful of sugar help the flagellum go
      round?
AB  - It is doubtful that diffusion can deliver sufficient ATP from the mitochondria to
      sustain activity at the distal end of the sperm flagellum. Glycolytic enzymes
      bound to the fibrous sheath could provide energy along the flagellum at the point
      it is required. An obligatory role for glycolysis is supported by the lack of
      progressive motility in sperm from mice where the gene for sperm-specific
      glyceraldehyde-3-phosphate dehydrogenase (GAPDHs) had been 'knocked out'. Here, I
      review some evidence against this idea. First, pure diffusion from the
      mitochondrion is likely to be adequate in species with smaller sperm, and it is
      possible that rapid ATP delivery required in larger sperm could be achieved by an
      adenylate kinase shuttle. Second, experience with alpha-chlorohydrin demonstrates
      that sperm can remain motile with normal ATP concentrations despite inhibition of
      GAPDHs; adverse effects only occur if glucose is added and high levels of
      glycolytic intermediates accumulate. These observations undermine the GAPDHs
      knockout mouse as evidence for an essential role of local glycolysis. Third,
      sperm from many species can remain motile for long periods in sugar-free media
      and excepting dog sperm, evidence that gluconeogenesis is a possible explanation,
      is weak. In most species, it is unlikely that local glycolysis is the only way
      that ATP can be supplied to the distal flagellum.

PMID- 16407454
TI  - Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in
      Apc-minus mice.
AB  - Sulforaphane (SFN) is an isothiocyanate from broccoli that induces phase 2
      detoxification enzymes. We recently reported that SFN acts as a histone
      deacetylase (HDAC) inhibitor in human colon cancer cells in vitro, and the
      present study sought to extend these findings in vivo. In mice treated with a
      single oral dose of 10 mumol SFN, there was significant inhibition of HDAC
      activity in the colonic mucosa after 6 h, and immunoblots revealed a concomitant
      increase in acetylated histones H3 and H4, which returned to control levels by 48
      h. Longer-term treatment with SFN in the diet resulted in levels of acetylated
      histones and p21(WAF1) in the ileum, colon, prostate, and peripheral blood
      mononuclear cells that were elevated compared with controls. Consistent with
      these findings, SFN suppressed tumor development in Apc(min) mice, and there was
      an increase in acetylated histones in the polyps, including acetylated histones
      specifically associated with the promoter region of the P21 and bax genes. These
      results provide the first evidence for HDAC inhibition by SFN in vivo and imply
      that such a mechanism might contribute to the cancer chemoprotective and
      therapeutic effects of SFN, alone or in combination with other HDAC inhibitors
      currently undergoing clinical trials.

PMID- 16407455
TI  - Regeneration of lesioned entorhino-hippocampal axons in vitro by combined
      degradation of inhibitory proteoglycans and blockade of Nogo-66/NgR signaling.
AB  - Damaged axons do not regenerate after axotomy in the adult mammalian central
      nervous system (CNS). This may be due to local inhibitory factors at the site of
      injury, such as overexpression of chondroitin sulfate (CS) proteoglycans (CSPG),
      and the presence of myelin-associated inhibitors (MAI). To overcome CSPG- or
      myelin-induced inhibition, strategies based on extrinsic and intrinsic treatments
      have been developed. For example, NEP1-40 is a synthetic peptide that promotes
      axonal regeneration by blocking Nogo-66/NgR interaction and chondroitinase ABC
      (ChABC), which degrades CS, thereby also promoting axon regrowth. Here, we
      examined whether the combination of these complementary strategies facilitates
      regeneration of the lesioned entorhino-hippocampal pathway (EHP) in slice
      cultures. In this model, overexpressed CSPG and MAI impaired axon regrowth, which
      mimics regeneration failure in vivo. Both CS cleavage with ChABC and NEP1-40
      strongly facilitated the regrowth of entorhinal axons after axotomy, permitting
      the re-establishment of synaptic contacts with target cells. However, the
      combined treatment did not improve the regeneration induced by ChABC alone, and
      the delayed treatment of ChABC, but not NEP1-40, had a less pronounced effect on
      axonal regrowth compared with acute treatment. These results provide insight into
      the development of new assays and strategies to enhance axon regeneration in
      injured cortical connections.

PMID- 16407457
TI  - Patch clamp reveals powerful blockade of the mitochondrial permeability
      transition pore by the D2-receptor agonist pramipexole.
AB  - The dopamine-D2-agonist pramipexole (PPX) was tested for blocking mitochondrial
      permeability transition (PT) in order to give a possible explanation for its
      neuroprotective effect seen in PPX-treated Parkinson's disease patients. Patch
      clamp techniques for studying single-channel currents in the inner mitochondrial
      membrane and large-amplitude swelling of energized mitochondria were used to
      study PPX action on the permeability transition pore (PTP), a key player in the
      mitochondrial route of the apoptotic cascade. Identity of the PTP was proven by
      measuring the concentration-response relation for cyclosporin A-blockade (IC50=26
      nM). PPX inhibits the PTP reversibly with an IC50 of 500 nM, which is close to
      the values determined earlier as plasma concentrations after PPX medication in
      patients. Interaction of PPX with the PTP is further supported by demonstrating
      that it abolished Ca2+-triggered swelling in functionally intact mitochondria.
      Blockade of the PTP by PPX was attenuated by increasing concentrations of
      inorganic phosphate and by acidification. We suggest that PPX could exert part of
      its neuroprotective effect by inhibition of the PTP and thus, probably, blocking
      of the mitochondrial pathway of the apoptosis cascade.

PMID- 16407458
TI  - Cluster headache in women: relation with menstruation, use of oral
      contraceptives, pregnancy, and menopause.
AB  - In contrast with migraine, little is known about the relation between cluster
      headache and menstrual cycle, oral contraceptives, pregnancy, and menopause. A
      population based questionnaire study was performed among 224 female cluster
      headache patients, and the possible effect of hormonal influences on cluster
      headache attacks studied. For control data, a similar but adjusted questionnaire
      was sent to healthy volunteers and migraine patients. It was found that
      menstruation, use of oral contraceptives, pregnancy, and menopause had a much
      smaller influence on cluster headache attacks than in migraine. Cluster headache
      can, however, have a large impact on individual women, for example to refrain
      from having children.

PMID- 16407456
TI  - G protein-associated, specific membrane binding sites mediate the neuroprotective
      effect of dehydroepiandrosterone.
AB  - The neurosteroid dehydroepiandrosterone (DHEA) at 1 nM protects NMDA-/GABAA
      receptor negative neural crest-derived PC12 cells from apoptosis. We now report
      that membrane-impermeable DHEA-BSA conjugate replaces unconjugated DHEA in
      protecting serum-deprived PC12 cells from apoptosis (IC50=1.5 nM). Protection
      involves phosphorylation of the prosurvival factor Src and induction of the anti
      apoptotic protein Bcl-2 and is sensitive to pertussis toxin. Binding assays of
      [3H]DHEA on isolated PC12 cell membranes revealed saturation within 30 min and
      binding of DHEA with a Kd of 0.9 nM. A similar binding activity was detectable in
      isolated membranes from rat hippocampus and from normal human adrenal chromaffin
      cells. The presence of DHEA-specific membrane binding sites was confirmed by flow
      cytometry and confocal laser microscopy of DHEA-BSA-FITC stained cells. In
      contrast to estrogens and progestins, glucocorticoids and androgens displaced
      DHEA from its membrane binding sites but with a 10-fold lower affinity than DHEA
      (IC50=9.3 and 13.6 nM, respectively). These agents acted as pure antagonists,
      blocking the antiapoptotic effect of DHEA as well as the induction of Bcl-2
      proteins and Src kinase activation. In conclusion, our findings suggest that
      neural crest-derived cells possess specific DHEA membrane binding sites coupled
      to G proteins. Binding to these sites confers neuroprotection.

PMID- 16407459
TI  - Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Accurate
      inference and estimation in population genomics.
AB  - Both intra- and interspecific genomic comparisons have revealed local
      similarities in the level and frequency of mutational variation, as well as in
      patterns of gene expression. This autocorrelation between measurements leads to
      violations of assumptions of independence in many statistical methods, resulting
      in misleading and incorrect inferences. Here I show that autocorrelation can be
      due to many factors and is present across the genome. Using a one-dimensional
      spatial stochastic model, I further show how previous results can be employed to
      correct for autocorrelation along chromosomes in population and comparative
      genomics research. When multiple hypothesis tests are autocorrelated, I
      demonstrate that a simple correction can lead to increased power in statistical
      inference. I present a preliminary analysis of population genomic data from
      Drosophila simulans to show the ubiquity of autocorrelation and applicability of
      the methods proposed here.

PMID- 16407460
TI  - Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Genome
      wide search of gene conversions in duplicated genes of mouse and rat.
AB  - Gene conversion is considered to play important roles in the formation of genomic
      makeup such as homogenization of multigene families and diversification of
      alleles. We devised two statistical tests on quartets for detecting gene
      conversion events. Each "quartet" consists of two pairs of orthologous sequences
      supposed to have been generated by a duplication event and a subsequent
      speciation of two closely related species. As example data, EnsEMBL mouse and rat
      cDNA sequences were used to obtain a genome-wide picture of gene conversion
      events. We extensively sampled 2,641 quartets that appear to have resulted from
      duplications after the divergence of primates and rodents and before mouse-rat
      speciation. Combination of our new tests with Sawyer's and Takahata's tests
      enhanced the detection sensitivity while keeping false positives as few as
      possible. About 18% (488 quartets) were shown to be highly positive for gene
      conversion using this combined test. Out of them, 340 (13% of the total) showed
      signs of gene conversion in mouse sequence pairs. Those gene conversion-positive
      gene pairs are mostly linked in the same chromosomes, with the proportion of
      positive pairs in the linked and unlinked categories being 15% and 1%,
      respectively. Statistical analyses showed that (1) the susceptibility to gene
      conversion correlates negatively with the physical distance, especially the
      frequency of 29% was observed for gene pairs whose distances are smaller than 55
      kb; (2) the occurrence of gene conversions does not depend on the transcriptional
      direction; (3) small gene families consisting of between three and six contiguous
      genes are highly prone to gene conversion; and (4) frequency of gene conversions
      greatly varies depending on functional categories, and cadherins favor gene
      conversion, while vomeronasal receptors type 1 and immunoglobulin V-type proteins
      disfavor it. These findings will be useful to deepen the understanding of the
      roles of gene conversion.

PMID- 16407461
TI  - The evolutionary rate of a protein is influenced by features of the interacting
      partners.
AB  - Rates of protein evolution are thought to be influenced by features of protein
      protein interaction (PPI). However, the most important features of interaction
      for determining the evolutionary rate are poorly understood. Here, we consider
      four categories for PPIs in Saccharomyces cerevisiae. Properties we consider are
      the extent to which proteins interact with proteins of the same function or
      different function (DF) and the extent to which these interactions involve
      connections in the dense part or sparse part (SP) of a PPI network. Our findings
      are that proteins with DF-SP interactions evolve at the slowest rate of all the
      proteins examined.

PMID- 16407462
TI  - Peroxisome proliferator-activated receptor alpha and gamma ligands differentially
      affect smooth muscle cell proliferation and migration.
AB  - Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are expressed
      in smooth muscle cells (SMCs). This study was designed to compare the effects of
      PPARalpha and PPARgamma on SMC proliferation and migration and to determine how
      they operate. Treatment of SMCs from porcine coronary artery revealed that
      mitogen-stimulated DNA synthesis was blocked by the PPARalpha ligand 4-chloro-6
      (2,3-xylidino)-2-pyrimidinylthioacetic acid (WY14,643) and 15-deoxy-Delta(12,14)
      prostaglandin J(2) (15d-PGJ(2)) (a putative PPARgamma agonist) but not by the
      PPARgamma agonist rosiglitazone or the PPARbeta/delta ligand 2-methyl-4-((4
      methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy
      acetic acid (GW501516). Inhibition of DNA synthesis by clofibrate and 2-(4-(2-(1
      cyclohexanebutyl-3-cyclohexylureido)ethyl)phenylthio)-2-methylproprionic acid
      (GW7647) confirmed that SMC proliferation is affected by PPARalpha. This
      conclusion was supported by the fact that WY14,643 also inhibited the
      proliferation of H4IIE hepatoma cells (expressing only PPARalpha) but not A10
      SMCs (expressing only PPARgamma1). In contrast, the effective inhibition of all
      cell types with 15d-PGJ(2) indicated that this compound probably operates via a
      PPARgamma-independent mechanism. Interestingly, rosiglitazone did not inhibit DNA
      synthesis of either H4IIE or A10 cells, suggesting that the activation of
      PPARgamma does not influence cell proliferation. Phosphorylation of cyclin
      dependent kinase 2 and expression of proliferating cell nuclear antigen were
      inhibited by WY14,643 but not by rosiglitazone or 15d-PGJ(2), indicating that
      PPARalpha prevents progression into S phase. Although rosiglitazone did not block
      SMC proliferation, it (like WY14,643) reduced neointimal hyperplasia in vitro.
      This observation can be rationalized by the fact that both WY14,643 and
      rosiglitazone inhibit SMC migration, probably through matrix metalloproteinase 9.
      Our study therefore shows that selective interference with mediators of cell
      cycle progression and cell migration via activation of PPARs may prevent growth
      related vascular diseases such as restenosis and atherosclerosis.

PMID- 16407463
TI  - Tonic nociceptinergic inputs to neurons in the hypothalamic paraventricular
      nucleus contribute to sympathetic vasomotor tone and water and electrolyte
      homeostasis in conscious rats.
AB  - Central administration of nociceptin/orphanin FQ (N/OFQ) produces bradycardia,
      hypotension, diuresis, and antinatriuresis in rats. Because N/OFQ peptide (NOP)
      receptors exist in the paraventricular nucleus (PVN) of the hypothalamus, we
      hypothesized that N/OFQ acts in the PVN to alter cardiovascular and renal
      function. To test this premise, N/OFQ (10 and 100 pmol) or artificial
      cerebrospinal fluid (vehicle) was microinjected into the right PVN of conscious,
      chronically instrumented rats infused i.v. with isotonic saline. After injection,
      N/OFQ, but not vehicle, dose-dependently decreased renal sympathetic nerve
      activity (RSNA) and increased urine flow rate. At 100 pmol, N/OFQ also decreased
      urinary sodium and potassium excretion and increased free water clearance. In
      separate groups, the diuretic response to N/OFQ injection into the PVN was
      blunted in chronic bilaterally renal denervated rats and abolished in intact rats
      continuously infused i.v. with [Arg(8)]vasopressin (60 fmol/kg/min). Finally, in
      other studies bilateral microinjection of the NOP receptor antagonist
      [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101; 300 pmol) into the PVN increased
      heart rate and RSNA and decreased urine flow rate without altering electrolyte
      excretion. Pretreatment of separate rats with UFP-101 (300 pmol, PVN) blocked the
      N/OFQ-evoked (100 pmol) cardiovascular, renal sympathetic nerve, and renal
      excretory responses. Together, these findings demonstrate that in conscious rats
      activation of NOP receptors in the PVN by N/OFQ produces bradycardia, renal
      sympathoinhibition, and water diuresis. Moreover, UFP-101 blocks a tonically
      active inhibitory influence of endogenous N/OFQ on central sympathetic outflow
      and vasopressin pathways which arise from the PVN to affect heart rate and urine
      output.

PMID- 16407464
TI  - Differential effects of passive immunization with nicotine-specific antibodies on
      the acute and chronic distribution of nicotine to brain in rats.
AB  - Vaccination against nicotine blocks or attenuates nicotine-related behaviors
      relevant to addiction in rats. Passive immunization with nicotine-specific
      antibodies is an alternative to vaccination with the potential advantages of
      allowing control of antibody dose and affinity. In the current study, the effects
      of two antibodies on the distribution of nicotine to brain were evaluated during
      chronic nicotine administration in rats; the monoclonal antibody Nic311 (K(d) =
      60 nM) and nicotine-specific antiserum (K(d) = 1.6 nM). Nicotine was administered
      via repeated i.v. bolus doses over 2 days and antibody was administered during
      the first day. Neither antibody appreciably reduced the chronic accumulation of
      nicotine in brain, despite high protein binding of nicotine in serum (98.9%) and
      a 73% reduction in the unbound serum nicotine concentration with the highest
      Nic311 dose. However, both antibodies substantially reduced the early
      distribution of nicotine to brain 5 min after a dose. The higher affinity
      antibody was no more effective than Nic311. The highest Nic311 dose produced
      serum antibody levels 10 times higher than those reported with vaccination. The
      efficacy of Nic311 was dose-related, with the highest dose producing a 76%
      decrease in the early distribution of nicotine to brain. These findings, along
      with previous data, suggest that the primary effect of passive immunization is to
      slow, rather than prevent, the distribution of nicotine to brain. In the setting
      of chronic nicotine dosing, antibodies with a moderate affinity for nicotine
      produced substantial effects on the early distribution of nicotine to brain and
      were as effective as higher affinity antibodies.

PMID- 16407465
TI  - NADPH-induced contractions of mouse aorta do not involve NADPH oxidase: a role
      for P2X receptors.
AB  - Reactive oxygen species elicit vascular effects ranging from acute dilatation
      because of hydrogen peroxide-mediated opening of K(+) channels to contraction
      arising from superoxide-dependent inactivation of endothelium-derived nitric
      oxide. Given that NADPH oxidases are major sources of superoxide in the vascular
      wall, this study examined the effects of exogenous NADPH, a substrate of these
      enzymes, on superoxide generation and isometric tone in mouse isolated aortic
      rings. NADPH caused concentration-dependent increases in superoxide generation
      (measured by lucigenin-enhanced chemiluminescence) and vascular tone (isometric
      tension recordings). However, surprisingly, whereas oxidized NADP(+) was unable
      to support superoxide production, it was equally as effective as reduced NADPH at
      stimulating vasocontraction. In addition, an NADPH oxidase inhibitor,
      diphenyleneiodonium, markedly attenuated NADPH-induced superoxide production, yet
      had no effect on vasocontractions to NADPH. In contrast, a broad specificity P2X
      receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, as
      well as the P2X1 selective antagonist, NF023, markedly attenuated both
      endothelium-dependent and -independent vasocontractions to NADPH, as did the P2X
      desensitizing agent alpha,beta-methylene-ATP. Importantly, alpha,beta-methylene
      ATP had no effect on superoxide production induced by NADPH. In conclusion, these
      findings suggest little role for NADPH oxidase-derived superoxide in the
      contractile effects of NADPH in the mouse aorta. Rather, NADPH seems to act as an
      agonist at two distinct P2X receptor populations; one located on the endothelium
      and the other on smooth muscle layer, both of which ultimately lead to
      contraction.

PMID- 16407466
TI  - A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine
      production by facilitating transient receptor potential melastatin 4 channel
      activity.
AB  - 3,5-Bis(trifluoromethyl)pyrazole derivative (BTP2) or N-[4-3, 5
      bis(trifluromethyl)pyrazol-1-yl]-4-methyl-1,2,3-thiadiazole-5-carboxamide (YM
      58483) is an immunosuppressive compound that potently inhibits both Ca2+ influx
      and interleukin-2 (IL-2) production in lymphocytes. We report here that BTP2
      dosedependently enhances transient receptor potential melastatin 4 (TRPM4), a
      Ca2+-activated nonselective (CAN) cation channel that decreases Ca2+ influx by
      depolarizing lymphocytes. The effect of BTP2 on TRPM4 occurs at low nanomolar
      concentrations and is highly specific, because other ion channels in T
      lymphocytes are not significantly affected, and the major Ca2+ influx pathway in
      lymphocytes, ICRAC, is blocked only at 100-fold higher concentrations. The
      efficacy of BTP2 in blocking IL-2 production is reduced approximately 100-fold
      when preventing TRPM4-mediated membrane depolarization, suggesting that the BTP2
      mediated facilitation of TRPM4 channels represents the major mechanism for its
      immunosuppressive effect. Our results demonstrate that TRPM4 channels represent a
      previously unrecognized key element in lymphocyte Ca2+ signaling and that their
      facilitation by BTP2 supports cell membrane depolarization, which reduces the
      driving force for Ca2+ entry and ultimately causes the potent suppression of
      cytokine release.

PMID- 16407467
TI  - A molecular mechanism for the anti-inflammatory effect of taurine-conjugated 5
      aminosalicylic acid in inflamed colon.
AB  - In previous reports, a novel colon-specific prodrug, 5-aminosalicyltaurine (5-ASA
      Tau) administered orally, is successfully delivered to and liberates 5
      aminosalicylic acid (5-ASA) and taurine in the inflamed large intestine of rats.
      Furthermore, the prodrug ameliorates the 2,4,6-trinitrobenzene-sulfonic acid
      induced colitis, and taurine acts not only as a carrier but also as an active
      therapeutic agent. In this study, we investigated the anti-inflammatory
      properties of the prodrug at a molecular level. After rectal administration of
      taurine, formation of taurine chloramine (TauCl) in the inflamed colonic tissue
      was examined using high-performance liquid chromatography. In human colon
      epithelial cell lines, nuclear factor-kappaB (NF-kappaB) activity was accessed
      using an NF-kappaB-dependent luciferase reporter gene. Protein levels were
      monitored by Western blotting. DNA binding activity of the NF-kappaB subunit p65
      was determined using a DNA binding assay kit. A millimolar level of TauCl was
      formed in the inflamed tissue. TauCl inhibited tumor necrosis factor (TNF)
      dependent NF-kappaB activation by modifying thiol(s) on p65 and blocking DNA
      binding. In addition, 5-ASA inhibited phosphorylation of p65 at serine 536, which
      is critical for transcriptional activity of NF-kappaB. Furthermore, combined
      TauCl/5-ASA treatment additively inhibited TNF-dependent NF-kappaB activation.
      Together, our data suggest that the colon-specific carrier taurine contributes to
      the clinical effect of the prodrug by potentiating the inhibitory effect of the
      active ingredient 5-ASA on a major proinflammatory signal, TNF-dependent NF
      kappaB activation in the inflamed large intestine.

PMID- 16407468
TI  - A nonpeptide antagonist reveals a highly glycosylated state of the rabbit kinin
      B1 receptor.
AB  - The inducible kinin B1 receptor is emerging as an attractive therapeutic target
      for the treatment of pain and inflammation. Although many studies described its
      regulation at the transcriptional level, little is known about the maturation of
      the B1 receptor. Using two human embryonic kidney (HEK) 293 cell lines stably
      expressing rabbit B1 receptors tagged with the yellow fluorescent protein at the
      C terminus (B1R-YFP) or the N-terminal myc epitope (myc-B1R), we showed that
      receptors are mainly retained in a perinuclear compartment and detectable as low
      glycosylated species under control conditions. Interference with the ubiquitin
      proteasome pathway function (proteasome inhibitors, coexpression with dominant
      negative ubiquitin) blocked B1 receptor degradation and amplified its
      intracellular accumulation. A potent nonpeptide antagonist specifically increased
      the abundance of highly glycosylated B1R-YFP forms at the cell surface
      (accessible to chymotrypsin digestion in intact cells); this compound augmented
      low-glycosylated receptors in brefeldin A-treated cells, supporting the
      hypothesis that it reaches a newly synthesized receptor in the endoplasmic
      reticulum. Cell-impermeant peptide or low-affinity nonpeptide B1 receptor
      antagonists failed to influence the level of highly glycosylated receptors.
      Chemical chaperones stabilized all B1R-YFP species and up-regulated endogenous B1
      receptors expressed at the surface of rabbit smooth muscle cells. Although myc
      B1Rs behaved similarly to B1R-YFP in most aspects, antibody-based detection
      assays failed to reveal highly glycosylated species of this construct. Taken
      together, these results show that B1 receptors overexpressed in HEK 293 cells are
      degraded by the proteasome. Furthermore, a pharmacological chaperone highlights
      the existence of a highly N-glycosylated form of the rabbit kinin B1 receptor at
      the cell surface.

PMID- 16407469
TI  - 2-cyano-3,12-dioxooleana-1,9(11)-diene-28-oic acid disrupts microtubule
      polymerization: a possible mechanism contributing to apoptosis.
AB  - The semisynthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid
      (CDDO) has several biological activities, including the induction of apoptosis in
      many cancer cell lines. To identify potential protein targets, immobilized
      biotinylated CDDO was used to screen the proteome of a human lymphoma cell line
      (U937) sensitive to CDDO-induced apoptosis. Tubulin was identified as one of
      several putative targets of CDDO. CDDO was shown to selectively bind to tubulin,
      with a dissociation constant of approximately 7 microM, and to disrupt
      microtubules both in vivo and in vitro. CDDO inhibits tubulin polymerization in
      vitro, possibly through interactions with a hydrophobic site on beta-tubulin. The
      CDDO-tubulin interaction may also involve a reversible 1,4-addition with a
      protein sulfhydryl group. Unlike other known spindle poisons, CDDO does not
      result in a temporal increase in the mitotic index. Rather, CDDO seems to
      initiate apoptosis early in M phase.

PMID- 16407470
TI  - A two-component model for counts of infectious diseases.
AB  - We propose a stochastic model for the analysis of time series of disease counts
      as collected in typical surveillance systems on notifiable infectious diseases.
      The model is based on a Poisson or negative binomial observation model with two
      components: a parameter-driven component relates the disease incidence to latent
      parameters describing endemic seasonal patterns, which are typical for infectious
      disease surveillance data. An observation-driven or epidemic component is modeled
      with an autoregression on the number of cases at the previous time points. The
      autoregressive parameter is allowed to change over time according to a Bayesian
      changepoint model with unknown number of changepoints. Parameter estimates are
      obtained through the Bayesian model averaging using Markov chain Monte Carlo
      techniques. We illustrate our approach through analysis of simulated data and
      real notification data obtained from the German infectious disease surveillance
      system, administered by the Robert Koch Institute in Berlin. Software to fit the
      proposed model can be obtained from http://www.statistik.lmu.de/ approximately
      mhofmann/twins.

PMID- 16407471
TI  - Age and sex affect human muscle fibre adaptations to heavy-resistance strength
      training.
AB  - This study assessed age and sex effects on muscle fibre adaptations to heavy
      resistance strength training (ST). Twenty-two young men and women (20-30 years
      old) and 18 older men and women (65-75 years old) completed 9 weeks of heavy
      resistance knee extension exercises with the dominant leg 3 days week(-1); the
      non-dominant leg served as a within-subject, untrained control. Bilateral vastus
      lateralis muscle biopsies were obtained before and after ST for analysis of type
      I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type
      distribution. One-repetition maximum (1-RM) strength was also assessed before and
      after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in
      the trained leg of young men, type I and IIa fibres in young women, type IIa
      fibres in older men, and type IIx fibres in older women (all P<0.05). Analysis of
      fibre type distribution revealed a significant increase in the percentage of type
      I fibres (P<0.05) along with a decrease in type IIx fibres (P=0.054) after ST
      only in young women. There were no significant changes in muscle fibre CSA or
      fibre type distribution in the untrained leg for any group. All groups displayed
      significant increases in 1-RM (27-39%; all P<0.01). In summary, ST led to
      significant increases in 1-RM and type II fibre CSA in all groups; however, age
      and sex influence specific muscle fibre subtype responses to ST.

PMID- 16407472
TI  - Remote myocardium gene expression after 30 and 120 min of ischaemia in the rat.
AB  - The aim of the present study was to investigate how early the onset of ischaemia
      induced changes in gene expression is in remote myocardium, and whether these
      changes would be different for left and right ventricles. Wistar rats (n=27) were
      randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and
      sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and
      left intraventricular (IV) septal ischaemia (35.5+/-0.6% of LV mass). LCA
      ligation induced transient LV systolic dysfunction and sustained biventricular
      slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP)
      was upregulated in the LV at 30 (+370+/-191%) and 120 min (+221+/-112%), whilst
      in the right ventricle (RV) this was only significant at 120 min (+128+/-39%).
      Hipoxia-inducible factor 1alpha and interleukin 6 overexpression positively
      correlated with BNP. Inducible NO synthase upregulation was present in both
      ventricles at 120 min (LV, +327+/-195%; RV, +311+/-122%), but only in the RV at
      30 min (+256+/-88%). Insulin-like growth factor 1 increased in both ventricles at
      30 (RV, +59+/-18%; LV, +567+/-192%) and 120 min (RV, +69+/-33%; LV, +120+/-24%).
      Prepro-endothelin-1 was upregulated in the RV at 120 min (+77+/-25%). Ca2+
      handling proteins were selectively changed in the LV at 120 min (sarcoplasmic
      reticulum Ca2+ ATPase, 53+/-7%; phospholamban, +31+/-4%; Na+-Ca2+ exchanger, 31+/
      6%), while Na+-H+ exchanger was altered only in the RV (-79+/-5%, 30 min; +155+/
      70%, 120 min). Tumour necrosis factor-alpha and angiotensin converting enzyme
      were not significantly altered. A very rapid modulation of remote myocardium gene
      expression takes place during myocardial ischaemia, involving not only the LV but
      also the RV. These changes are different in the two ventricles and in the same
      direction as those observed in heart failure.

PMID- 16407473
TI  - Variations in carotid arterial compliance during the menstrual cycle in young
      women.
AB  - The effect of menstrual cycle phase on arterial elasticity is controversial. In
      10 healthy women (20.6+/-1.5 years old, mean+/-s.d.), we investigated the
      variations in central and peripheral arterial elasticity, blood pressure (carotid
      and brachial), carotid intima-media thickness (IMT), and serum oestradiol and
      progesterone concentrations at five points in the menstrual cycle (menstrual, M;
      follicular, F; ovulatory, O; early luteal, EL; and late luteal, LL). Carotid
      arterial compliance (simultaneous ultrasound and applanation tonometry) varied
      cyclically, with significant increases from the values seen in M (0.164+/-0.036
      mm2 mmHg-1) and F (0.171+/-0.029 mm2 mmHg-1) to that seen in the O phase (0.184+/
      0.029 mm2 mmHg-1). Sharp declines were observed in the EL (0.150+/-0.033 mm2 mmHg
      1) and LL phases (0.147+/-0.026 mm2 mmHg-1; F=8.51, P<0.05). Pulse wave velocity
      in the leg (i.e. peripheral arterial stiffness) did not exhibit any significant
      changes. Fluctuations in carotid arterial elasticity correlated with the balance
      between oestradiol and progesterone concentrations. No significant changes were
      found in carotid and brachial blood pressures, carotid artery lumen diameter, or
      IMT throughout the menstrual cycle. These data provide evidence that the elastic
      properties of central, but not peripheral, arteries fluctuate significantly with
      the phases of the menstrual cycle.

PMID- 16407474
TI  - Effects of mechanosensitive ion channels on ventricular electrophysiology:
      experimental and theoretical models.
AB  - The heart is an electrically driven mechanical pump, somewhat like an electric
      motor. Interestingly, like an electric motor in 'dynamo mode', the heart can also
      convert mechanical stimuli into electrical signals. This feedback from cardiac
      mechanics to electrical activity involves mechanosensitive ion channels, whose
      properties and pathophysiological relevance are reviewed in the context of
      experimental and theoretical modelling of ventricular beat-by-beat
      electromechanical function.

PMID- 16407475
TI  - Integrating modelling and experiments to assess dynamic musculoskeletal function
      in humans.
AB  - Magnetic resonance imaging, bi-plane X-ray fluoroscopy and biomechanical
      modelling are enabling technologies for the non-invasive evaluation of muscle,
      ligament and joint function during dynamic activity. This paper reviews these
      various technologies in the context of their application to the study of human
      movement. We describe how three-dimensional, subject-specific computer models of
      the muscles, ligaments, cartilage and bones can be developed from high-resolution
      magnetic resonance images; how X-ray fluoroscopy can be used to measure the
      relative movements of the bones at a joint in three dimensions with submillimetre
      accuracy; how complex 3-D dynamic simulations of movement can be performed using
      new computational methods based on non-linear control theory; and how
      musculoskeletal forces derived from such simulations can be used as inputs to
      elaborate finite-element models of a joint to calculate contact stress
      distributions on a subject-specific basis. A hierarchical modelling approach is
      highlighted that links rigid-body models of limb segments with detailed finite
      element models of the joints. A framework is proposed that integrates subject
      specific musculoskeletal computer models with highly accurate in vivo
      experimental data.

PMID- 16407476
TI  - Multiscale modelling of human gastric electric activity: can the
      electrogastrogram detect functional electrical uncoupling?
AB  - During recent years there has been a growing interest in the assessment of
      gastric electrical health through cutaneous abdominal recordings. The analysis of
      such recordings is largely limited to an inspection of frequency dynamics, and
      this has raised doubts as to whether functional gastric electrical uncoupling can
      be detected using this technique. We describe here a computational approach to
      the problem in which the equations governing the underlying physics of the
      problem have been solved over an anatomically detailed human torso geometry.
      Cellular electrical activity was embedded within a stomach tissue model, and this
      was coupled to the torso using an equivalent current source approach. Simulations
      were performed in which normal and functionally uncoupled (through the
      introduction of an ectopic antral pacemaker) gastric slow wave activity was
      present, and corresponding cutaneous electrogastrograms were produced. These were
      subsequently analysed using the currently recommended techniques, and it was
      found that the functionally uncoupled situation was indistinguishable from normal
      slow wave activity using this approach.

PMID- 16407477
TI  - Computational models of structure-function relationships in the pulmonary
      circulation and their validation.
AB  - The pulmonary airway, arterial, venous and capillary networks are vast complex
      branching and converging systems that are mechanically coupled to the surrounding
      lung tissue. Early studies that examined vascular or airway geometry relied on
      measurements from casts, but medical imaging now enables measurement of the lung
      in vivo, at controlled lung volumes. The high-quality data that imaging provides
      have prompted development of increasingly sophisticated models of the geometry of
      the airway and pulmonary vascular trees. The accurate spatial relationships
      between airway, vessel and tissue in these imaging-derived models are necessary
      for computational analysis that aims to elucidate regional airway-vessel-tissue
      interactions. Predictions of blood flow through multiscale imaging-derived models
      of the pulmonary arteries and capillary bed reveal geometry-dependent patterns of
      perfusion in response to gravity and lung orientation that cannot be predicted
      with simplified, summary representations of the pulmonary transport trees.
      Validation of such predictions against measures from functional imaging holds
      significant potential for explaining and differentiating normal and disease
      related heterogeneity in regional blood flow calculated using perfusion imaging.

PMID- 16407478
TI  - Visual area V5/MT remembers "what" but not "where".
AB  - Priming for motion direction has been shown to depend upon the functional
      integrity of extrastriate area V5/MT. Its retinotopic organization and the
      interactions recently found between motion adaptation and misperceived
      localization may suggest, for this area, a role for priming of spatial position
      in addition to the established priming of motion direction. Disruption of V5/MT
      with repetitive transcranial magnetic stimulation during the intertrial interval
      had the effect of abolishing priming of motion direction but no effect in priming
      of spatial position. These effects cannot be explained in terms of perception or
      task demands but only in terms of the effects of information irrelevant to the
      correct performance of the task stored over the intertrial interval. We suggest
      that the attribute of spatial position might be stored in short-term memory
      either in earlier areas of the motion pathways such as V3 or in higher cortical
      areas traditionally associated with the analysis of spatial information, for
      example, posterior parietal cortex or the frontal eye fields.

PMID- 16407479
TI  - The neural correlates of declining performance with age: evidence for age-related
      changes in cognitive control.
AB  - The neural system involved in cognitive control includes the anterior cingulate
      cortex (ACC) and the lateral prefrontal cortex (PFC). Neural activity within
      these structures is sensitive to aging. We investigated the hypothesis that
      decline in performance with age results in increased cognitive control, as
      indexed by greater activity within the ACC and lateral PFC. Using positron
      emission tomography we measured neural activity during a range of verbal decision
      making tasks in 16 subjects aged 37-83 years. Conditions were separated
      behaviorally on the basis of their sensitivity to aging. This allowed the
      comparison of age-dependent and age-independent conditions, revealing the neural
      correlates of age-dependent decline in performance. We then modeled the
      relationship between age, decision type, performance, and frontal lobe activity.
      ACC activity was independently predicted by age and decision-making accuracy,
      indicating that in older individuals ACC response is more sensitive to declining
      performance. We also found strong functional connectivity between the ACC and
      lateral PFC and observed that activation of the lateral PFC was qualitatively
      different over time in different age groups. Thus, the ACC and lateral PFC show
      distinct responses to age-related decline in decision-making performance. This
      suggests that greater cognitive control is employed as individuals age and their
      performance declines.

PMID- 16407480
TI  - Auditory processing deficits in dyslexia: task or stimulus related?
AB  - The nature of the fundamental deficit underlying reading disability is the
      subject of a long-standing debate. We previously found that dyslexics with
      additional learning difficulties (D-LDs) perform poorly in simple auditory tasks.
      We now tried to determine whether these deficits relate to stimulus or task
      complexity. We found that the degree of impairment was dependent on task rather
      than stimulus complexity. D-LDs could adequately detect and identify mild
      frequency changes in simple pure tones and minimal phonemic changes in complex
      speech sounds when task required only simple same-different discriminations.
      However, when task required the identification of the direction of frequency
      change or the ordinal position of a repeated tonal or speech stimulus, D-LDs'
      performance substantially deteriorated. This behavioral pattern suggests that D
      LDs suffer from a similar type of deficits when processing speech and nonspeech
      sounds. In both cases, the extent of difficulties is determined by the structure
      of the task rather than by stimulus composition or complexity.

PMID- 16407481
TI  - Metabotropic glutamate receptors modulate the NMDA- and AMPA-induced gene
      expression in neocortical interneurons.
AB  - Group I metabotropic glutamate receptors (mGluRIs) can be colocalized with
      ionotropic glutamate receptors in postsynaptic membranes. We have investigated
      whether mGluRIs alter the gene transcription induced by N-methyl-D-aspartate
      (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA)
      receptors in rat neocortical gamma-aminobutyric acid (GABA) interneurons. In
      cultures of dissociated interneurons, the mGluRI antagonists LY367385 and MPEP
      reduced the increase in phosphorylation of the transcription factor CREB induced
      by NMDA as well as the expression of the proenkephalin (PEnk) gene. In contrast,
      they enhanced the AMPA-induced CREB phosphorylation and PEnk gene expression.
      Stimulation of the mGluRIs was due to network activity that caused the release of
      endogenous glutamate and could be blocked by tetrodotoxin. In organotypic
      cultures of neocortex, endogenous glutamate enhanced the PEnk gene expression by
      acting on NMDA and AMPA receptors. These effects were modulated via mGluRIs. In
      patch-clamp experiments and in biochemical studies on receptor density,
      stimulation of mGluRIs acutely affected NMDA receptor currents but had no long
      term effect on NMDA receptor density at the cell surface. In contrast,
      stimulation of mGluRIs decreased the density of AMPA receptors located at the
      cell surface. Our results suggest that mGluRIs regulate the glutamate-induced
      gene expression in neocortical interneurons in a physiologically relevant manner.

PMID- 16407482
TI  - Progressive proliferative and dysplastic typhlocolitis in aging syrian hamsters
      naturally infected with Helicobacter spp.: a spontaneous model of inflammatory
      bowel disease.
AB  - Helicobacter spp. have been implicated in a variety of gastrointestinal tract
      diseases, including peptic ulcer disease, gastric cancer, and inflammatory bowel
      disease (IBD), in humans and animals. Although most models of IBD are
      experimentally induced, spontaneous or natural models of IBD are rare. Herein, we
      describe a long-term study of chronic, progressive lesions that develop in the
      distal portion of the large bowel of unmanipulated Syrian hamsters naturally
      infected with Helicobacter spp. Twenty-four Syrian hamsters of three age groups
      (group A, 1 month [n = 4], group B, 7-12 months [n = 12], group C, 18-24 months
      [n = 12]), underwent complete postmortem examination. Results of microbial
      isolation and polymerase chain reaction and restriction fragment length
      polymorphism analyses confirmed the presence of Helicobacter spp. infection in
      the distal portion of the large bowel of all animals. Additionally, confounding
      pathogens, such as Clostridium difficile, Lawsonia intracellularis, and Giardia
      spp. that can cause proliferative enteritis, were absent in the hamsters of this
      study. Histopathologic scores for inflammation (P < 0.01), hyperplasia (P <
      0.01), and dysplasia (P < 0.05) were significantly higher in the ileocecocolic
      (ICC) junction of animals in group C, relative to group A. Dysplastic lesions of
      various grades were detected in 5 of 11 hamsters in group C. Interestingly, the
      segment of the bowel that is usually colonized by Helicobacter spp. in hamsters
      had the most severe lesions. One hamster of group C developed a malignant fibrous
      histiocytoma, whereas another hamster developed a round cell sarcoma originating
      from the ICC junction. Thus, lesions in the distal portion of the large bowel of
      aging hamsters naturally colonized with Helicobacter spp. warrants developing the
      hamster as an animal model of IBD and potentially IBD-related cancer.

PMID- 16407483
TI  - Feline large granular lymphocyte (LGL) lymphoma with secondary leukemia: primary
      intestinal origin with predominance of a CD3/CD8(alpha)(alpha) phenotype.
AB  - Clinicopathologic and immunophenotypic characteristics of large granular
      lymphocyte (LGL) neoplasia in 21 cats were examined. All cats were domestic short
      (19) or long hair (2) with a mean age of 9.3 years at diagnosis. Increased
      peripheral blood LGL counts were present in 18/21 cats. Neutrophilia (12/21 cats)
      and increased serum liver enzymes (7/12), total and direct bilirubin (7/13), BUN
      (5/14), and creatinine (2/14) were observed. Cats usually presented with advanced
      disease and none survived longer than 84 days (mean 18.8 days) postdiagnosis.
      Cytologically, LGLs had a mature (6/21), immature (13/21), or mixed (2/21)
      morphology. Necropsy lesions consisted of neoplastic lymphoid infiltrates in the
      jejunum, ileum, and duodenum in decreasing order of frequency. In the small
      intestine, mucosal ulceration (9/13) and epitheliotropism of neoplastic cells
      (9/13) were common. Neoplastic infiltrates were also present in the mesenteric
      lymph nodes (13/13), liver (12/13), spleen (8/13), kidneys (5/7), and bone marrow
      (5/7). A T cell phenotype (CD3epsilon+) characterized LGL neoplasia in 19/21
      cases. A CD8alphaalpha+ cytotoxic/suppressor phenotype was present in 12/19 T
      cell tumors, 2 had a CD4+CD8alphaalpha phenotype, 3 had a CD4-CD8- phenotype, and
      2 were CD4+ helper T cells. CD8beta chain expression was not detected in any
      instance. In two cats, a B or T cell origin could not be established. CD103 was
      expressed by 11 of 19 (58%) of the lymphomas tested. The immunophenotypic
      features shared by neoplastic LGLs in the cat and feline intestinal
      intraepithelial lymphocytes (IELs) support a small intestinal IEL origin for
      feline LGL lymphoma.

PMID- 16407484
TI  - Oligodendroglial dysplasia in two bullmastiff dogs.
AB  - Leukodystrophies are inherited neurological disorders involving central nervous
      system white matter. They are uncommon in animals but a few, breed-specific
      entities have been described. In 2002, two young-adult, purebred Bullmastiff dogs
      from central New York State presented to their referring veterinarians displaying
      moderate to severe ataxia of all limbs, spastic tetraparesis that was worse in
      the pelvic limbs, and a diffuse, action-related, whole-body tremor. Clinical
      signs were insidious in onset and slowly progressive. Anatomic diagnoses
      considered were a C1-C5 lesion or, based on the whole-body tremor, a diffuse
      central nervous system disorder. No gross lesions were apparent in the brain or
      spinal cord. Histopathologically, numerous, multifocal, sharply demarcated,
      small, ovoid to angular areas of myelin pallor (plaques) were present throughout
      the major white matter tracts of the brainstem and spinal cord. These plaques,
      which often were traversed by axons, did not stain with luxol fast blue for
      myelin and were associated with minimal astrocytosis. Ultrastructural findings
      include occasional hypertrophic glia in white matter, rare unmyelinated segments
      of axons, and focal proliferation of tubule-containing cytoplasmic glial cell
      processes (oligodendroglial). The described clinical and morphological findings
      and age of onset are similar to the well-characterized, presumably hereditary,
      bovine syndrome known as Charolais ataxia or oligodendroglial dysplasia. This
      article presents the first description of a leukodystrophy in the Bullmastiff
      breed and the first report of oligodendroglial dysplasia in animals other than
      Charolais cattle.

PMID- 16407486
TI  - Canine intraneural perineurioma.
AB  - A 6-year-old castrated German Shepherd Dog was presented with a 6-month history
      of progressive, nonpainful, left pelvic limb paresis. Magnetic resonance imaging
      revealed atrophy of left-sided epaxial and hypaxial muscles from L5-L7 and an
      enlarged L5 spinal nerve. Exploratory hemi-laminectomy revealed focally and
      cylindrically thickened L5 and L6 nerve roots. Histologic evaluation of a
      surgical biopsy specimen from the L6 dorsal nerve root, and the L5 nerve roots
      after later amputation revealed distended hypercellular fascicles. This
      distension was due to widely separated axons surrounded by concentric
      lamellations formed by neoplastic perineurial cells and their processes. These
      pseudo-onion bulbs were separated from each other by a basophilic myxoid stroma.
      The perineurioma cell processes were immunonegative for S-100 (alpha and beta
      chains) and collagen IV, but were immunoreactive for laminin. The central axons
      were also immunoreactive for NF-200 and S-100. The proliferative index of the
      perineurioma cells, as determined by MIB-1 immunoreactivity, was about 3%.
      Ultrastructurally, the widely separated, interdigitating perineurioma cell
      processes were connected by desmosomal-like junctional complexes to form
      continuous circles. Their processes were covered by a discontinuous basal lamina.
      Each centrally placed axon was normally, thinly, or completely unmyelinated and
      was surrounded by a normal Schwann cell. These morphologic and immunologic
      features distinguish this lesion from hypertrophic neuropathy and were consistent
      with intraneural perineurioma.

PMID- 16407485
TI  - Expression of terminal differentiation proteins defines stages of mouse mammary
      gland development.
AB  - Immunohistochemical analysis using paraffin-embedded specimens is the method of
      choice to evaluate protein expression at a cellular level while preserving tissue
      architecture in normal and neoplastic tissues. Current knowledge of the
      expression of terminal differentiation markers in the mouse mammary gland relies
      on the evaluation of frozen tissues by use of immunofluorescence. We assessed
      changes in patterns of expression of terminal differentiation markers throughout
      the development of the mouse mammary gland in paraffin-embedded tissues. The
      expression of alpha-smooth muscle actin (SMA) and keratins (K) 5, 8/18, and 14
      was influenced by the development stage of the mammary gland. Expression of K5
      and SMA was restricted to basal cells. Keratin 14 was consistently expressed by
      mammary basal cells, and was detected in scattered luminal cells from 13.5 days
      after conception through puberty. Labeling for K8/18 of luminal cells was
      heterogeneous at all times. Heterogeneous expression patterns in luminal cells
      suggest this layer has cells with a variety of biological functions. The absence
      of K6 expression at any stage of the development of the mammary gland was
      confirmed by use of reverse transcriptase-polymerase chain reaction analysis,
      which indicates that this intermediate filament is not a marker of the mammary
      gland stem cell. Finally, consistent with results of earlier studies, keratins 1,
      10, 13, and 15, and filaggrin, involucrin, and loricrin were not detected at any
      stage of mammary gland development.

PMID- 16407487
TI  - Vaccine-associated rhabdomyosarcoma with spinal epidural invasion and pulmonary
      metastasis in a cat.
AB  - A 7-year-old, female, domestic medium-haired cat had a recurrent deep dermal mass
      in the interscapular region after initial surgical removal 3 months earlier. The
      cat had received a killed rabies vaccine and a five-in-one vaccine in the same
      area about 2 months prior to the first surgery. The relapsed mass was diagnosed
      as vaccine-associated sarcoma. The cat was euthanized 2 months later because of
      hind limb paralysis. At necropsy, multiple, poorly demarcated, nodular masses
      were seen in the muscles around the shoulders, neck, and thoracic vertebrae.
      Pulmonary metastasis and spinal epidural invasion at T1-T3 with regional cord
      compression and malacia were observed. Microscopically, the masses consisted of
      interwoven bundles of spindle cells with prominent multinucleated giant cell
      formation. The neoplastic cells stained strongly positive for myoglobin, and
      moderately but variably positive for vimentin, desmin, and alpha- smooth muscle
      actin. Phosphotungstic acid-hematoxylin staining revealed cytoplasmic striations
      in scattered tumor cells. The tumor was considered a vaccine-associated
      rhabdomyosarcoma.

PMID- 16407488
TI  - West Nile Flavivirus Polioencephalomyelitis in a harbor seal (Phoca vitulina).
AB  - A 12-year-old male harbor seal presented with progressive signs of neurologic
      dysfunction including head tremors, muzzle twitching, clonic spasms, and
      weakness. Lesions included polioencephalomyelitis with glial nodules, spheroids,
      neuronophagia, ring hemorrhages, and a few neutrophils. Neurons, fibers, and
      glial nodules were multifocally colonized with intracytoplasmic West Nile
      flavivirus antigens that were demonstrated using indirect immunohistochemical
      analysis. Flavivirus on cultured cells also was isolated and was identified by
      use of monoclonal antibodies and reverse transcriptase-polymerase chain reaction
      analysis. Clinical signs of disease and lesion morphology and distribution were
      similar to those of equine West Nile virus infection. Similar to horses, alpacas,
      humans, dogs, and reptiles, seals can be dead-end hosts of West Nile virus.

PMID- 16407489
TI  - Ossifying fibroma in a miniature rex rabbit (Oryctolagus cuniculus).
AB  - In humans and animals, ossifying fibroma is a benign neoplasm that most
      frequently affects the mandible, often resulting in cosmetic deformities and
      malocclusion. It is considered rare in animals and most frequently affects young
      horses. A surgical biopsy of a solitary mass located beneath the gingiva in the
      right maxillary region, which had overgrown teeth and expanded the adjacent hard
      palate from a 6-year-old miniature Rex rabbit was submitted for light microscopic
      examination. The submitted incisional biopsy specimen was pale pink, firm, and
      nodular. Histopathologically, the neoplasm was composed of fibroblastic cells
      separated by abundant collagen. The neoplastic cells were interwoven with
      osteoblasts surrounding islands of mineralized, bony matrix containing few,
      widely spaced, often empty, lacunae. Minimal inflammation was present. Based on
      the histopathologic features, the tumor was diagnosed as an ossifying fibroma. To
      our knowledge, this is the first report of an ossifying fibroma in a rabbit.

PMID- 16407490
TI  - An unusual case of generalized soft-tissue mineralization in a suckling foal.
AB  - An atypical case of severe soft-tissue mineralization in a 3-week-old foal from a
      herd of Andalusian horses is described. The herd clinical history and the
      laboratory findings were compatible with a diagnosis of secondary
      hyperparathyroidism due to a mineral imbalance in the diet (low calcium and high
      phosphorus intake). Mares showed a marked increase in serum parathyroid hormone
      (PTH) approximately 10 times normal levels. Serum PTH was marginally elevated in
      foals. Clinical signs (unthriftiness, painful joints, lameness in one or more
      limbs, and stiff gait) were more pronounced in foals than in mares. Two foals
      died and necropsy of one of them revealed extensive soft-tissue mineralization of
      arterial walls and pulmonary parenchyma. Clinical signs in mares and foals
      resolved by 4 weeks after diet adjustment.

PMID- 16407491
TI  - Immunohistochemical evaluation of inflammatory infiltrate in the skin and lung of
      lambs naturally infected with sheeppox virus.
AB  - The present study describes immunophenotypic characteristics of inflammatory
      infiltrate in the skin and lung of lambs naturally infected with sheeppox virus
      (SPV). Three lambs revealed typical cutaneous and pulmonary lesions of sheeppox.
      Histologically, cutaneous and pulmonary lesions consisted of hyperplastic and/or
      degenerative changes in the epithelium with mononuclear cells, neutrophils, and
      typical sheeppox cells (SPCs), which had a vacuolated nucleus and marginated
      chromatin with occasional granular intracytoplasmic inclusions. The inflammatory
      infiltrate in pox lesions in both skin and lung was characterized by the presence
      of MHC II+ dendritic cells, CD4+, CD8+, gammadelta+ T cells, IgM+ cells, and
      CD21+ cells. Loss of expression of MHC I and MHC II antigens was observed in the
      affected areas of skin and lung. SPCs, stained with anti-SPV antibody, were also
      positive for CD14 and CD172A, antigens expressed on monocytes and macrophages.
      CD14 and CD172A negative SPCs were considered to be SPV infected degenerated
      epithelial cells or fibroblasts.

PMID- 16407492
TI  - Disseminate Cryptococcosis in a guenon (Cercopithecus ascanius).
AB  - A 23-year-old captive-bred red-tailed guenon (Cercopithecus ascanius) with a
      brief history of inappetence, lethargy, and seizures was submitted for necropsy.
      On postmortem examination, multiple cryptococcomas were identified in brain and
      heart. Cryptococcus neoformans organisms were also identified microscopically in
      kidney, eye, and pancreas. Fungal yeast formed rare pseudohyphae. The histologic
      diagnosis of cryptococcosis was confirmed by a positive test for C. neoformans
      antigen in a serum sample. Immunohistochemical staining confirmed that
      macrophages were the principal inflammatory cell in brain lesions and often
      contained phagocytosed yeast. As disseminate cryptococcosis is often associated
      with immune suppression, serology and immunohistochemical staining for simian
      immunodeficiency virus were performed but showed no evidence of SIV infection.

PMID- 16407493
TI  - Characterization of the cDNA Encoding alphaIIb and beta3 in normal horses and two
      horses with Glanzmann thrombasthenia.
AB  - Glanzmann thrombasthenia (GT) is an inherited, intrinsic platelet defect
      characterized by a quantitative or qualitative change in the platelet
      glycoprotein complex IIb-IIIa (integrin alpha(IIb)beta3). The subunits are
      encoded by separate genes and both subunits must be expressed for a stable
      complex to form on the platelet surface; therefore, a defect in either gene can
      result in GT.

PMID- 16407494
TI  - Double-labeling immunofluorescence: an alternative to detect multiple antigens in
      tissue sections.

PMID- 16407496
TI  - Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules
      and papillary thyroid carcinoma for gene groups.
AB  - CONTEXT: There are an increasing number of studies analyzing gene expression
      profiles in various benign and malignant thyroid tumors. This creates the
      opportunity to validate results obtained from one microarray study with those
      from other data sets. This process requires rigorous methods for accurate
      comparison. OBJECTIVE: The ability to compare data sets derived from different
      Affymetrix GeneChip generations and the influence of intra- and interindividual
      comparisons of gene expression data were evaluated to build multigene classifiers
      of benign thyroid nodules to verify a previously proposed papillary thyroid
      carcinoma (PTC) classifier and to look for molecular pathways essential for PTC
      oncogenesis. METHODS: Gene expression profile data sets from autonomously
      functioning and cold thyroid nodules and from PTC were analyzed by support vector
      machines. GenMAPP analysis was used for PTC data analysis to examine the
      expression patterns of biologically relevant gene sets. RESULTS: Only
      intraindividual reference samples allowed the identification of subtle changes in
      the expression patterns of relevant signaling cascades, such as the MAPK pathway
      in PTC. Using an artificial intelligence approach, the autonomously functioning
      and cold thyroid nodule multigene classifiers were derived and evaluated by cross
      comparisons. CONCLUSION: We recommend defining classifiers within one generation
      of gene chips and subsequently checking them across different array generations.
      Using this approach, we have demonstrated the specificity of a previously
      reported PTC classifier on an independent collection of benign tumors. Moreover,
      we propose multigene classifiers for different types of benign thyroid nodules.

PMID- 16407497
TI  - Adult sertoli cells are not terminally differentiated in the Djungarian hamster:
      effect of FSH on proliferation and junction protein organization.
AB  - Sertoli cell number is considered to be stable and unmodifiable by hormones after
      puberty in mammals, although recent data using the seasonal breeding adult
      Djungarian hamster (Phodopus sungorus) model challenged this assertion by
      demonstrating a decrease in Sertoli cell number after gonadotropin depletion and
      a return to control levels following 7 days of FSH replacement. The present study
      aimed to determine whether adult Sertoli cells are terminally differentiated
      using known characteristics of cellular differentiation, including proliferation,
      junction protein localization, and expression of particular maturational markers,
      in the Djungarian hamster model. Adult long-day (LD) photoperiod (16L:8D)
      hamsters were exposed to short-day (SD) photoperiod (8L:16D) for 11 wk to
      suppress gonadotropins and then received exogenous FSH for up to 10 days. Sertoli
      cell proliferation was assessed by immunofluorescence by the colocalization of
      GATA4 and proliferating cell nuclear antigen and quantified by stereology.
      Markers of Sertoli cell maturation (immature, cytokeratin 18 [KRT18]; mature,
      GATA1) and junction proteins (actin, espin, claudin 11 [CLDN11], and tight
      junction protein 1 [TJP1, also known as ZO-1]) also were localized using confocal
      immunofluorescence. In response to FSH treatment, proliferation was upregulated
      within 2 days compared with SD controls (90% vs. 0.2%, P < 0.001) and declined
      gradually thereafter. In LD hamsters, junction proteins colocalized at the basal
      aspect of Sertoli cells, consistent with inter-Sertoli cell junctions, and were
      disordered within the Sertoli cell cytoplasm in SD animals. Exogenous FSH
      treatment promptly restored localization of these junction markers to the LD
      phenotype. Protein markers of maturity remain consistent with those of adult
      Sertoli cells. It is concluded that adult Sertoli cells are not terminally
      differentiated in the Djungarian hamster and that FSH plays an important role in
      governing the differentiation process. It is proposed that Sertoli cells can
      enter a transitional state, exhibiting features common to both undifferentiated
      and differentiated Sertoli cells.

PMID- 16407498
TI  - WNT pathways in the neonatal ovine uterus: potential specification of endometrial
      gland morphogenesis by SFRP2.
AB  - Endometrial glands are critical for uterine function and develop between birth
      (Postnatal Day [P] 0) and P56 in the neonatal ewe. Endometrial gland
      morphogenesis or adenogenesis involves the site-specific budding differentiation
      of the glandular epithelium from the luminal epithelium followed by their
      coiling/branching development within the stroma of the intercaruncular areas of
      the endometrium. To determine whether WNT signaling regulates endometrial
      adenogenesis, the WNT signaling system was studied in the neonatal ovine uterus.
      WNT5A, WNT7A, and WNT11 were expressed in the uterine epithelia, whereas WNT2B
      was in the stroma. The WNT receptors FZD2 and FZD6 and coreceptor LRP6 were
      detected in all uterine cells, and FZD6 was particularly abundant in the
      endometrial epithelia. Secreted FZD-related protein-2 (SFRP2), a WNT antagonist,
      was not detected in the P0 uterus, but was abundant in the aglandular caruncular
      areas of the endometrium between P7 and P56. Exposure of ewes to estrogens during
      critical developmental periods inhibits or retards endometrial adenogenesis.
      Estrogen-induced disruption of endometrial adenogenesis was associated with
      reduction or ablation of WNT2B, WNT7A, and WNT11, and with an increase in WNT2
      and SFRP2 mRNA, depending on exposure period. Collectively, results implicate the
      canonical and noncanonical WNT pathways in regulation of postnatal ovine uterine
      development and endometrial adenogenesis. Expression of SFRP2 in aglandular
      caruncular areas may inhibit the WNT signaling pathway, thereby concentrating WNT
      signaling and restricting endometrial adenogenesis in the intercaruncular areas
      of the uterus. Further, estrogen-induced inhibition of adenogenesis may be
      mediated by a reduction in WNT signaling caused by aberrant induction of SFRP2
      and loss of several critical WNTs.

PMID- 16407499
TI  - Expression and relationship of male reproductive ADAMs in mouse.
AB  - A number of a disintegrin and metalloprotease (ADAM) family members are expressed
      in mammalian male reproductive organs such as testis and epididymis. These
      reproductive ADAMs are divided phylogenically into three major groups: ADAMs 1,
      4, 6, 20, 21, 24, 25, 26, 29, 30, and 34 (the first group); ADAMs 2, 3, 5, 27,
      and 32 (the second group); and ADAMs 7 and 28 (the third group). Previous mouse
      knockout studies indicate that ADAM1, ADAM2, and ADAM3 have intricate
      expressional relationships, playing critical roles in fertilization. In the
      present study, we analyzed processing, biochemical characteristics, localization,
      and expressional relationship of the previously-unexplored, second-group ADAMs
      (ADAM5, ADAM27, and ADAM32). We found that all of the three ADAMs are made as
      precursors in the testis and processed during epididymal maturation, and that
      ADAM5 and ADAM32, but not ADAM27, are located on the sperm surface. Using sperm
      from Adam2(-/-) and Adam3(-/-) mice, we found that, among the three ADAMs, the
      level of ADAM5 is modestly and severely reduced in Adam3 and Adam2 knockout
      sperm, respectively. Further, we analyzed ADAM7, an epididymis-derived sperm
      surface ADAM from the separate phylogenetic group, in the knockout sperm. We
      found that the level of ADAM7 is also significantly reduced in both Adam2 and
      Adam3-null sperm. Taken together, our results suggest a novel expressional
      relationship of ADAM5 and ADAM7 with ADAM2 and ADAM3, which play critical roles
      in fertilization.

PMID- 16407500
TI  - Myometrial apoptosis: activation of the caspase cascade in the pregnant rat
      myometrium at midgestation.
AB  - In the present study, we determined the contribution of myometrial hyperplasia,
      hypertrophy, and apoptosis to uterine growth during pregnancy. The changes in two
      endogenous markers of cell replication, proliferating cell nuclear antigen (PCNA)
      protein expression and bromodeoxyuridine (BrdU) incorporation, were studied.
      Myocyte hypertrophy was assessed by measuring the protein:DNA ratio. The
      expression levels of antiapoptotic regulatory proteins (BCL2 and BCL2L1) and
      enzymes involved in apoptosis (caspases 3, 6, 7, 9, and 10) were assessed by
      immunoblotting throughout gestation and postpartum. Myometrial cell apoptosis was
      determined by TUNEL staining and DNA fragmentation assays. Both BrdU
      incorporation and PCNA labeling were elevated in early pregnant myometrium and
      decreased dramatically after midgestation, with a simultaneous increase in
      cellular hypertrophy. Levels of BCL2 were high during early gestation, followed
      by significantly elevated levels of BCL2L1 at midgestation. The expression of
      caspase 10 in myometrial samples declined from a high nonpregnant level to a
      complete loss at early gestation. The cleaved forms of caspases (CC) 3, 6, 7, and
      9, as well as poly(ADP-ribose)polymerase-1, were undetectable in the myometrial
      samples at early or late gestation but were transiently elevated at midgestation.
      Immunohistochemical staining of CC3 confirmed the activation of the caspase
      cascade, but TUNEL-positive staining or the increase in DNA fragmentation was not
      detected. Collectively, two distinct phases of myometrial growth were observed:
      myocyte hyperplasia associated with an increase in antiapoptotic proteins during
      the first half of gestation, and cellular hypertrophy during the second part of
      gestation. The transition between these phases was associated with transient
      activation of the caspase cascade that triggered the differentiation of uterine
      smooth muscle.

PMID- 16407501
TI  - Biological effects of recombinant human zona pellucida proteins on sperm
      function.
AB  - The initial interaction between gametes takes place at the level of the sperm
      surface and the zona pellucida (ZP), the extracellular matrix of the egg in
      mammals. Successful fertilization requires the proper molecular recognition of
      the ZP by the sperm. Recently, human ZP was demonstrated to be composed of four
      proteins: ZP1, ZP2, ZP3, and ZP4. The goals of this study were to determine the
      effects of recombinant human ZP2, ZP3, and ZP4 on human sperm acrosomal
      exocytosis and sperm motility. Exposure of sperm to ZP proteins, alone or in
      combination, promoted acrosomal exocytosis in a time-dependent manner. This
      effect occurred in parallel with a considerable decrease in progressive motility,
      coincident with an increase in nonprogressive sperm motility. An analysis of
      kinetic parameters of ZP-treated sperm demonstrated that a characteristic
      motility pattern could be defined by values of curvilinear velocity > 63.9 mum/s
      and linearity <or= 15.5%. A strong correlation between curvilinear velocity and
      the amplitude of lateral head displacement was also observed. The incidence of
      sperm having these particular kinetic parameters increased after exposure to ZP
      proteins. These studies of two processes involved in sperm penetration through
      the ZP confirm that zona glycoproteins promote acrosomal exocytosis and now
      establish an additional role for these components as modifiers of sperm motility.

PMID- 16407502
TI  - Donor centrosome regulation of initial spindle formation in mouse somatic cell
      nuclear transfer: roles of gamma-tubulin and nuclear mitotic apparatus protein 1.
AB  - During the process of spindle-chromosome complex depletion in the oocyte, it is
      unclear whether both gamma-tubulin and nuclear mitotic apparatus protein 1
      (NUMA1), which are required for mitotic organization and spindle assembly, are
      removed. The role of the donor cell centrosome and donor nuclear NUMA1 in the
      initial spindle morphogenesis and chromosome remodeling also remains unclear. In
      the present study, we show that in the mouse, the level of gamma-tubulin in the
      poles and around the metaphase II spindle declines significantly, whereas only
      approximately 10% of NUMA1 is removed during spindle-chromosome complex depletion
      in the recipient oocyte. This process does not impede initial spindle
      morphogenesis and is regulated by the centrosome of the donor cumulus cell.
      Retaining the donor cell centrosome establishes a monopolar spindle, whereas
      prior removal of the centrosome by a narrow-bore micropipette leads to bipolar
      spindle formation. Our data show that the centrosome of the donor cell regulates
      initial spindle morphogenesis and that the donor cumulus cell NUMA1 compensates
      for the deficiency in recipient NUMA1 during the formation of metaphase-like
      structures after nuclear transfer. Full-term offspring of cloned mice were
      obtained after injection of donor cells only with a pipette having an inner
      diameter of 7-8 microm, which retained the donor cell centrosome. In contrast,
      removing the donor cell centrosome with a small pipette impaired preimplantation
      development and prevented full-term development. In conclusion, the initial
      spindle assembly of a metaphase-like spindle is regulated by the centrosome from
      the donor cell in the mouse.

PMID- 16407503
TI  - Images in clinical medicine. Milwaukee shoulder.

PMID- 16407504
TI  - Research in the hot zone.

PMID- 16407505
TI  - Bioterrorism--preparing to fight the next war.

PMID- 16407506
TI  - The burden of illness in international travelers.

PMID- 16407507
TI  - Spectrum of disease and relation to place of exposure among ill returned
      travelers.
AB  - BACKGROUND: Approximately 8 percent of travelers to the developing world require
      medical care during or after travel. Current understanding of morbidity profiles
      among ill returned travelers is based on limited data from the 1980s. METHODS:
      Thirty GeoSentinel sites, which are specialized travel or tropical-medicine
      clinics on six continents, contributed clinician-based sentinel surveillance data
      for 17,353 ill returned travelers. We compared the frequency of occurrence of
      each diagnosis among travelers returning from six developing regions of the
      world. RESULTS: Significant regional differences in proportionate morbidity were
      detected in 16 of 21 broad syndromic categories. Among travelers presenting to
      GeoSentinel sites, systemic febrile illness without localizing findings occurred
      disproportionately among those returning from sub-Saharan Africa or Southeast
      Asia, acute diarrhea among those returning from south central Asia, and
      dermatologic problems among those returning from the Caribbean or Central or
      South America. With respect to specific diagnoses, malaria was one of the three
      most frequent causes of systemic febrile illness among travelers from every
      region, although travelers from every region except sub-Saharan Africa and
      Central America had confirmed or probable dengue more frequently than malaria.
      Among travelers returning from sub-Saharan Africa, rickettsial infection,
      primarily tick-borne spotted fever, occurred more frequently than typhoid or
      dengue. Travelers from all regions except Southeast Asia presented with parasite
      induced diarrhea more often than with bacterial diarrhea. CONCLUSIONS: When
      patients present to specialized clinics after travel to the developing world,
      travel destinations are associated with the probability of the diagnosis of
      certain diseases. Diagnostic approaches and empiric therapies can be guided by
      these destination-specific differences.

PMID- 16407508
TI  - Efficacy and safety of benazepril for advanced chronic renal insufficiency.
AB  - BACKGROUND: Angiotensin-converting-enzyme inhibitors provide renal protection in
      patients with mild-to-moderate renal insufficiency (serum creatinine level, 3.0
      mg per deciliter or less). We assessed the efficacy and safety of benazepril in
      patients without diabetes who had advanced renal insufficiency. METHODS: We
      enrolled 422 patients in a randomized, double-blind study. After an eight-week
      run-in period, 104 patients with serum creatinine levels of 1.5 to 3.0 mg per
      deciliter (group 1) received 20 mg of benazepril per day, whereas 224 patients
      with serum creatinine levels of 3.1 to 5.0 mg per deciliter (group 2) were
      randomly assigned to receive 20 mg of benazepril per day (112 patients) or
      placebo (112 patients) and then followed for a mean of 3.4 years. All patients
      received conventional antihypertensive therapy. The primary outcome was the
      composite of a doubling of the serum creatinine level, end-stage renal disease,
      or death. Secondary end points included changes in the level of proteinuria and
      the rate of progression of renal disease. RESULTS: Of 102 patients in group 1, 22
      (22 percent) reached the primary end point, as compared with 44 of 108 patients
      given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in
      group 2 (60 percent). As compared with placebo, benazepril was associated with a
      43 percent reduction in the risk of the primary end point in group 2 (P=0.005).
      This benefit did not appear to be attributable to blood-pressure control.
      Benazepril therapy was associated with a 52 percent reduction in the level of
      proteinuria and a reduction of 23 percent in the rate of decline in renal
      function. The overall incidence of major adverse events in the benazepril and
      placebo subgroups of group 2 was similar. CONCLUSIONS: Benazepril conferred
      substantial renal benefits in patients without diabetes who had advanced renal
      insufficiency. (ClinicalTrials.gov number, NCT00270426.)

PMID- 16407509
TI  - A randomized trial of inhaled cyclosporine in lung-transplant recipients.
AB  - BACKGROUND: Conventional regimens of immunosuppressive drugs often do not prevent
      chronic rejection after lung transplantation. Topical delivery of cyclosporine in
      addition to conventional systemic immunosuppression might help prevent acute and
      chronic rejection events. METHODS: We conducted a single-center, randomized,
      double-blind, placebo-controlled trial of inhaled cyclosporine initiated within
      six weeks after transplantation and given in addition to systemic
      immunosuppression. A total of 58 patients were randomly assigned to inhale either
      300 mg of aerosol cyclosporine (28 patients) or aerosol placebo (30 patients)
      three days a week for the first two years after transplantation. The primary end
      point was the rate of histologic acute rejection. RESULTS: The rates of acute
      rejection of grade 2 or higher were similar in the cyclosporine and placebo
      groups: 0.44 episode (95 percent confidence interval, 0.31 to 0.62) vs. 0.46
      episode (95 percent confidence interval, 0.33 to 0.64) per patient per year,
      respectively (P=0.87 by Poisson regression). Survival was improved with
      aerosolized cyclosporine, with 3 deaths among patients receiving cyclosporine and
      14 deaths among patients receiving placebo (relative risk of death, 0.20; 95
      percent confidence interval, 0.06 to 0.70; P=0.01). Chronic rejection-free
      survival also improved with cyclosporine, as determined by spirometric analysis
      (10 events in the cyclosporine group and 20 events in the placebo group; relative
      risk of chronic rejection, 0.38; 95 percent confidence interval, 0.18 to 0.82;
      P=0.01) and histologic analysis (6 vs. 19 events, respectively; relative risk,
      0.27; 95 percent confidence interval, 0.11 to 0.67; P=0.005). The risks of
      nephrotoxic effects and opportunistic infection were similar for patients in the
      cyclosporine group and the placebo group. CONCLUSIONS: Inhaled cyclosporine did
      not improve the rate of acute rejection, but it did improve survival and extend
      periods of chronic rejection-free survival. (ClinicalTrials.gov number,
      NCT00268515.).

PMID- 16407510
TI  - Familial sinus bradycardia associated with a mutation in the cardiac pacemaker
      channel.
AB  - We found that sinus bradycardia in members of a large family was associated with
      a mutation in the gene coding for the pacemaker HCN4 ion channel. Pacemaker
      channels of the sinoatrial node generate spontaneous activity and mediate cyclic
      AMP (cAMP)-dependent autonomic modulation of the heart rate. The mutation
      associated with bradycardia is located near the cAMP-binding site; functional
      analysis found that mutant channels respond normally to cAMP but are activated at
      more negative voltages than are wild-type channels. These changes, which mimic
      those of mild vagal stimulation, slow the heart rate by decreasing the inward
      diastolic current. Thus, diminished function of pacemaker channels is linked to
      familial bradycardia.

PMID- 16407511
TI  - Clinical practice. Chronic daily headache.

PMID- 16407512
TI  - Treatment of acute lymphoblastic leukemia.

PMID- 16407513
TI  - Images in clinical medicine. Splenic and mediastinal calcifications in
      histoplasmosis.

PMID- 16407514
TI  - Case records of the Massachusetts General Hospital. Case 1-2006. A 64-year-old
      male lung-transplant recipient with fever, cough, hemoptysis, and abdominal pain.

PMID- 16407515
TI  - Optimizing ACE-inhibitor therapy for chronic kidney disease.

PMID- 16407516
TI  - Inhaled cyclosporine--a breath of fresh air?

PMID- 16407517
TI  - Reform of drug regulation--beyond an independent drug-safety board.

PMID- 16407518
TI  - Bacteria associated with bacterial vaginosis.

PMID- 16407519
TI  - Azithromycin versus penicillin for early syphilis.

PMID- 16407520
TI  - Cost-effectiveness of ICDs.

PMID- 16407521
TI  - Medicare and cost-effectiveness analysis.

PMID- 16407522
TI  - Primary prevention of sudden death in patients with lamin A/C gene mutations.

PMID- 16407523
TI  - Case 26-2005: loss of consciousness while jogging.

PMID- 16407524
TI  - Silicone pneumonitis after a cosmetic augmentation procedure.

PMID- 16407525
TI  - Regional genetic structuring and evolutionary history of the impala Aepyceros
      melampus.
AB  - Samples of 162 impala antelope (Aepyceros melampus) from throughout its
      distribution range in sub-Saharan Africa were surveyed using eight polymorphic
      microsatellite loci. Furthermore, 155 previously published mitochondrial DNA
      (mtDNA) sequences from the same localities were reanalyzed. Two subspecies of
      impala are presently recognized--the isolated black-faced impala (Aepyceros
      melampus petersi) in southwest Africa and the common impala (Aepyceros melampus
      melampus) abundant in southern and east Africa. All tests performed indicated
      significant genetic differentiation at the subspecific level. Furthermore,
      individual-based analyses split the common impala subspecies into two distinct
      genetic groups, conforming with regional geographic affiliation to southern or
      east Africa. This was supported by assignment tests, genetic distance measures,
      pairwise theta values, and analysis of molecular variance. We suggest that the
      presence of such previously unknown regional structuring within the subspecies
      reflects a pattern of colonization from a formerly large panmictic population in
      southern Africa toward east Africa. This scenario was supported by a progressive
      decline in population diversity indices toward east Africa and a significant
      increase in the quantity theta/(1 - theta). Both microsatellite and mtDNA data
      indicated a genetic distinctiveness of the Samburu population in Kenya.

PMID- 16407526
TI  - A blue variant in the rainbow trout, Oncorhynchus mykiss Walbaum.
AB  - A blue variant of the rainbow trout, which appeared in a French fish farm,
      displayed an iridescent body color that was cobalt blue on the back, lighter on
      the undersides, and silvery on the belly and which held up to adult stage. This
      color was supposed to result from a Tyndall effect involving a structural
      arrangement of melanin pigments because it disappeared when it was associated
      with a depigmenting gene. This blue variant appeared to be governed by an
      autosomal recessive gene. Blue fry survival and body weight were about 25% less
      than those of wild-type sibs, but no major problem was observed in further
      breeding performances, including reproduction. These features do not correspond
      with those of the blue variants previously described in the rainbow trout.

PMID- 16407527
TI  - Genetic diversity within and among sinai populations of three Ballota species
      (Lamiaceae).
AB  - Ballota undulata, Ballota kaiseri, and Ballota saxatilis are very rare (and
      endemic--B. kaiseri), threatened species growing in St. Catherine Protectorate,
      southern Sinai, Egypt. They are subjected to a number of threats that have caused
      populations to decline in both number and size. For the long-term survival of
      these species, an appropriate conservation strategy for the maintenance of their
      genetic variation should be developed. This study measures genetic diversity
      within and among populations of these Ballota species and determines the
      conservation implications of the results. The genetic analyses demonstrated that
      the three Ballota species maintain relatively high levels of genetic diversity
      (He = 0.195-0.317) and that most of the their genetic diversity was found within
      populations (GST = 0.045-0.099). Indirect estimates of historical gene flow for
      B. undulata and B. saxatilis were relatively high (Nm(W) = 5.25 and 3.37,
      respectively) but suggest that there is somewhat less gene movement among B.
      kaiseri populations (Nm(W) = 2.29). The levels of genetic diversity maintained
      within populations of the three Ballota species indicate that an appropriate
      sampling design for ex situ safeguarding should capture the majority of the
      genetic diversity found within these taxa.

PMID- 16407528
TI  - Genetic clines in the Bay of Biscay provide estimates of migration for Sardina
      pilchardus.
AB  - Nine allozymic loci in 1,635 individuals of Sardina pilchardus obtained at 33
      sites ranging from the North to the South limits of the Bay of Biscay were
      analyzed to provide a description of the genetic structure of the sardine
      population. Individual body size and age were also recorded and analyzed. In the
      study population, weak but significant genetic differences were found, and a
      cline was observed between multilocus heterozygosity and longitude. The cline was
      predominantly driven by allelic frequencies of two loci, PGM-1* and PEP-lt*, and
      using a cline model, we estimated a migration rate of 103.1 km/gen (dispersal
      distance per generation). In addition, we observed that the cline was linked to
      biological data such as mean length and mean age of the fish. Two hypotheses may
      explain this cline: mixing of two different populations in the Bay of Biscay or a
      selective process. The weak genetic differences, the important dispersal distance
      per generation, and the link between genetic and biological data suggest that
      selection is likely to be the primary factor that maintains the cline.

PMID- 16407529
TI  - The candidate gene, Clock, localizes to a strong spawning time quantitative trait
      locus region in rainbow trout.
AB  - We applied a candidate gene mapping approach to an existing quantitative trait
      loci (QTL) data set for spawning date in rainbow trout (Oncorynchus mykiss) to
      ascertain whether these genes could potentially account for any observed QTL
      effects. Several genes were chosen for their known or suspected roles in
      reproduction, circadian, or circannual timing, including salmon-type gonadotropin
      releasing hormone 3A and 3B (GnRH3A and GnRH3B), Clock, Period1, and
      arylalkylamine N-acetlytransferase-1 and -2 (AANAT-1 and AANAT-2). Genes were
      sequenced, and polymorphisms were identified in parents of two rainbow trout
      mapping families, one of which was used previously to detect spawn timing QTL.
      Interval mapping was used to identify associations between genetic markers and
      spawning date effects. Using a genetic map that was updated with 574 genetic
      markers (775 total), we found evidence for 11 significant or suggestive QTL
      regions. Most QTL were only localized within one of the parents; however, a
      strong QTL region was identified in both female and male parents on linkage group
      RT-8 that explained 20% and 50% of trait variance, respectively. The Clock gene
      mapped to this region. Period1 mapped to a region in the female parent associated
      with a marginal effect (P = .056) on spawn timing. Other candidate genes were not
      associated with significant QTL effects.

PMID- 16407530
TI  - Axonal growth and guidance defects in Frizzled3 knock-out mice: a comparison of
      diffusion tensor magnetic resonance imaging, neurofilament staining, and
      genetically directed cell labeling.
AB  - Previous work has identified axonal outgrowth and/or guidance defects in the
      brain and spinal cord of prenatal Frizzled3 (Fz3)(-/-) mice. To systematically
      explore the axonal defects in Fz3(-/-) mice and to compare techniques for the
      global assessment of axon tracts in the developing mouse, we have analyzed wild
      type and Fz3(-/-) brains using (1) diffusion tensor magnetic resonance imaging
      (muDTI), (2) neurofilament staining, and (3) two genetically directed neuronal
      labeling methods. Confirming and extending the previous work of Wang et al.
      (2002), we find that the following structures/tracts are absent or greatly
      reduced in the Fz3(-/-) brain: the anterior commissure, cerebral peduncle
      (corticospinal tract), corpus callosum, fornix, internal capsule (thalamocortical
      and corticothalamic tracts), stria medullaris, stria terminalis, and hippocampal
      commissure. An aberrant U-shaped fiber bundle immediately caudal to the optic
      tract connects the left and right sides of the Fz3(-/-) thalamus and likely
      represents a default pathway for thalamic axons that failed to enter the internal
      capsule. At embryonic day 18, labeling of cortical pyramidal cells with a yellow
      fluorescent protein reporter reveals widespread fragmentation of axons with no
      apparent loss of pyramidal cell bodies. Fragmentation likely represents one stage
      in the process that normally eliminates stalled or mistargeted axons. This work
      demonstrates the usefulness of muDTI and genetically directed neuronal labeling
      for the analysis of nervous system defects in the mouse.

PMID- 16407531
TI  - Kinetics of cerebral amyloid angiopathy progression in a transgenic mouse model
      of Alzheimer disease.
AB  - Cerebral amyloid angiopathy (CAA), the deposition of cerebrovascular beta-amyloid
      (Abeta) in the walls of arterial vessels, has been implicated in hemorrhagic
      stroke and is present in most cases of Alzheimer disease. Previous studies of the
      progression of CAA in humans and animal models have been limited to the
      comparison of pathological tissue from different brains at single time points.
      Our objective was to visualize in real time the initiation and progression of CAA
      in Tg2576 mice by multiphoton microscopy through cranial windows. Affected
      vessels were labeled by methoxy-X04, a fluorescent dye that selectively binds
      cerebrovascular beta-amyloid and plaques. With serial imaging sessions spaced at
      weekly intervals, we were able to observe the earliest appearance of CAA in
      leptomeningeal arteries as multifocal deposits of band-like Abeta. Over
      subsequent imaging sessions, we were able to identify growth of these deposits
      (propagation), as well as appearance of new bands (additional initiation events).
      Statistical modeling of the data suggested that as the extent of CAA progressed
      in this vascular bed, there was increased prevalence of propagation over
      initiation. During the early phases of CAA development, the overall pathology
      burden progressed at a rate of 0.35% of total available vessel area per day (95%
      confidence interval, 0.3-0.4%). The consistent rate of disease progression
      implies that this model is amenable to investigations of therapeutic
      interventions.

PMID- 16407532
TI  - Synaptotagmin IV does not alter excitatory fast synaptic transmission or fusion
      pore kinetics in mammalian CNS neurons.
AB  - Synaptotagmin IV (Syt IV) is a brain-specific isoform of the synaptotagmin
      family, the levels of which are strongly elevated after seizure activity. The
      dominant hypothesis of Syt IV function states that Syt IV upregulation is a
      neuroprotective mechanism for reducing neurotransmitter release. To test this
      hypothesis in mammalian CNS synapses, Syt IV was overexpressed in cultured mouse
      hippocampal neurons, and acute effects on fast excitatory neurotransmission were
      assessed. We found neurotransmission unaltered with respect to basal release
      probability, Ca2+ dependence of release, short-term plasticity, and fusion pore
      kinetics. In contrast, expression of a mutant Syt I with diminished Ca2+ affinity
      (R233Q) reduced release probability and altered the Ca2+ dependence of release,
      thus demonstrating the sensitivity of the system to changes in neurotransmission
      resulting from changes to the Ca2+ sensor. Together, these data refute the
      dominant model that Syt IV functions as an inhibitor of neurotransmitter release
      in mammalian neurons.

PMID- 16407533
TI  - Brain activity associated with expectancy-enhanced placebo analgesia as measured
      by functional magnetic resonance imaging.
AB  - In this study, a well established expectancy manipulation model was combined with
      a novel placebo intervention, a validated sham acupuncture needle, to investigate
      the brain network involved in placebo analgesia. Sixteen subjects completed the
      experiment. We found that after placebo acupuncture treatment, subjective pain
      rating reduction (pre minus post) on the placebo-treated side was significantly
      greater than on the control side. When we calculated the contrast that subtracts
      the functional magnetic resonance imaging (fMRI) signal difference between post
      treatment and pretreatment during pain application on placebo side from the same
      difference on control side [e.g., placebo (post - pre) - control (post - pre)],
      significant differences were observed in the bilateral rostral anterior cingulate
      cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal
      gyrus, and left inferior parietal lobule. The simple regression (correlation)
      analysis between each subject's fMRI signal difference of post-treatment and
      pretreatment difference on placebo and control side and the corresponding
      subjective pain rating difference showed that significant negative correlation
      was observed in the bilateral lateral/orbital prefrontal cortex, rACC,
      cerebellum, right fusiform, parahippocampus, and pons. These results are
      different from a previous study that found decreased activity in pain-sensitive
      regions such as the thalamus, insula, and ACC when comparing the response to
      noxious stimuli applied to control and placebo cream-treated areas of the skin.
      Our results suggest that placebo analgesia may be configured through multiple
      brain pathways and mechanisms.

PMID- 16407534
TI  - Late-onset leanness in mice with targeted ablation of melanin concentrating
      hormone neurons.
AB  - The observation that loss of orexin (hypocretin) neurons causes human narcolepsy
      raises the possibility that other acquired disorders might also result from loss
      of hypothalamic neurons. To test this possibility for body weight, mice with
      selective loss of melanin concentrating hormone (MCH) neurons were generated. MCH
      was chosen to test because induced mutations of the MCH gene in mice cause
      hypophagia and leanness. Mice with ablation of MCH neurons were generated using
      toxin (ataxin-3)-mediated ablation strategy. The mice appeared normal but, after
      7 weeks, developed reduced body weight, body length, fat mass, lean mass, and
      leptin levels. Leanness was characterized by hypophagia and increased energy
      expenditure. To study the role of MCH neurons on obesity secondary to leptin
      deficiency, we generated mice deficient in both ob gene product (leptin) and MCH
      neurons. Absence of MCH neurons in ob/ob mice improved obesity, diabetes, and
      hepatic steatosis, suggesting that MCH neurons are important mediators of the
      response to leptin deficiency. These data show that loss of MCH neurons can lead
      to an acquired leanness. This has implications for the pathogenesis of acquired
      changes of body weight and might be considered in clinical settings characterized
      by substantial weight changes later in life.

PMID- 16407535
TI  - Direct involvement of orexinergic systems in the activation of the mesolimbic
      dopamine pathway and related behaviors induced by morphine.
AB  - In this study, we investigated the role of orexinergic systems in dopamine
      related behaviors induced by the mu-opioid receptor agonist morphine in rodents.
      Extensive coexpression of tyrosine hydroxylase with orexin receptors was observed
      in the mouse ventral tegmental area (VTA). The levels of dopamine and its major
      metabolites in the nucleus accumbens were markedly increased by the
      microinjection of orexin A and orexin B into the VTA. The subcutaneous morphine
      induced place preference and hyperlocomotion observed in wild-type mice were
      abolished in mice that lacked the prepro-orexin gene. An intra-VTA injection of a
      selective orexin receptor antagonist SB334867A [1-(2-methylbenzoxazol-6-yl)-3
      [1.5]naphthyridin-4-yl urea] significantly suppressed the morphine-induced place
      preference in rats. Furthermore, the increased level of dialysate dopamine
      produced by morphine in the mouse brain was significantly decreased by deletion
      of the prepro-orexin gene. These findings provide new evidence that orexin
      containing neurons in the VTA are directly implicated in the rewarding effect and
      hyperlocomotion induced by morphine through activation of the mesolimbic dopamine
      pathway in rodents.

PMID- 16407536
TI  - Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA
      receptors is increased in the entorhinal cortex of chronically epileptic rats.
AB  - We have shown previously that when postsynaptic NMDA receptors are blocked, the
      frequency, but not amplitude, of spontaneous EPSCs (sEPSCs) at synapses in the
      entorhinal cortex is reduced by NMDA receptor antagonists, demonstrating that
      glutamate release is tonically facilitated by presynaptic NMDA autoreceptors. In
      the present study, we recorded sEPSCs using whole-cell voltage clamp in neurons
      in layer V in slices of the rat entorhinal cortex. Using specific antagonists for
      NR2A [(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4
      tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid] and NR2B [(alphaR, betaS)
      alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol
      hydrochloride (Ro 25-6981)] subunit-containing receptors, we confirmed that in
      slices from juvenile rats (4-6 weeks of age), the autoreceptor is predominantly
      of the NR1-NR2B subtype. In older (4-6 months of age) control animals, the effect
      of the NR2B antagonist was less marked, suggesting a decline in autoreceptor
      function with development. In slices from rats (aged 4-6 months) exhibiting
      spontaneous recurrent seizures induced with a lithium-pilocarpine protocol, Ro 25
      6981 again robustly reduced sEPSC frequency. The effect was equal to or greater
      than that seen in the juvenile slices and much more pronounced than that seen in
      the age-matched control animals. In all three groups, the NR2A antagonist was
      without effect on sEPSCs. These results suggest that there is a developmental
      decrease in NMDA autoreceptor function, which is reversed in a chronic epileptic
      condition. The enhanced autoreceptor function may contribute to seizure
      susceptibility and epileptogenesis in temporal lobe structures.

PMID- 16407537
TI  - Aldosterone target neurons in the nucleus tractus solitarius drive sodium
      appetite.
AB  - Sodium appetite can be enhanced by the adrenal steroid aldosterone via an unknown
      brain mechanism. A novel group of neurons in the nucleus tractus solitarius
      expresses the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which makes
      them selectively responsive to aldosterone. Their activation parallels sodium
      appetite in different paradigms of salt loss even in the absence of aldosterone.
      These unique aldosterone target neurons may represent a previously unrecognized
      central convergence point at which hormonal and neural signals can be integrated
      to drive sodium appetite.

PMID- 16407538
TI  - Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor
      protein (APP) and beta-secretase beta-site APP-cleaving enzyme.
AB  - sorLA is a recently identified neuronal receptor for amyloid precursor protein
      (APP) that is known to interact with APP and affect its intracellular transport
      and processing. Decreased levels of sorLA in the brain of Alzheimer's disease
      (AD) patients and elevated levels of amyloid-beta peptide (Abeta) in sorLA
      deficient mice point to the importance of the receptor in this neurodegenerative
      disorder. We analyzed APP cleavage in an APP-shedding assay and found that both
      sorLA and, surprisingly, a sorLA tail construct inhibited APP cleavage in a beta
      site APP-cleaving enzyme (BACE)-dependent manner. In line with this finding,
      sorLA and the sorLA tail significantly reduced secreted Abeta levels when BACE
      was overexpressed, suggesting that sorLA influences beta-cleavage. To understand
      the effect of sorLA on APP cleavage by BACE, we analyzed whether sorLA interacts
      with APP and/or BACE. Because both full-length sorLA and sorLA C-terminal tail
      constructs were functionally relevant for APP processing, we analyzed sorLA-APP
      for a potential cytoplasmatic interaction domain. sorLA and C99
      coimmunoprecipitated, pointing toward the existence of a new cytoplasmatic
      interaction site between sorLA and APP. Moreover, sorLA and BACE also
      coimmunoprecipitate. Thus, sorLA interacts both with BACE and APP and might
      therefore directly affect BACE-APP complex formation. To test whether sorLA
      impacts BACE-APP interactions, we used a fluorescence resonance energy transfer
      assay to evaluate BACE-APP interactions in cells. We discovered that sorLA
      significantly reduced BACE-APP interactions in Golgi. We postulate that sorLA
      acts as a trafficking receptor that prevents BACE-APP interactions and hence BACE
      cleavage of APP.

PMID- 16407539
TI  - Expression of a familial Alzheimer's disease-linked presenilin-1 variant enhances
      perforant pathway lesion-induced neuronal loss in the entorhinal cortex.
AB  - Alzheimer's disease (AD) is characterized by neuronal loss in the hippocampus and
      entorhinal cortex that is manifested by progressive memory impairment and
      cognitive decline. Autosomal-dominant, familial forms of AD (FAD) are caused by
      mutations in genes encoding amyloid precursor protein, presenilin-1 (PS1), and
      presenilin 2. Although it is established that expression of mutant PS1 variants
      leads to increased production of highly fibrillogenic amyloidbeta42 (Abeta42)
      peptides that deposit in the brains of patients with AD, the mechanism(s) by
      which Abeta deposition and expression of mutant genes induce lamina- and region
      specific vulnerability of neuronal populations is not known. We have examined the
      hypothesis that expression of transgene-encoded FAD-linked mutant PS1 variants in
      entorhinal cortex neurons exacerbates the vulnerability of these cells to lesion
      induced neuronal loss. To test this notion, we transected the perforant pathway
      (PP) of transgenic mice harboring either wild-type human PS1 (PS1HWT) or the FAD
      linked mutant PS1DeltaE9 variant and examined neuronal survival in layer II of
      the entorhinal cortex (ECL2). Remarkably, PP transections lead to marked
      reductions in the numbers of ECL2 neurons in the ECL2 of mice expressing mutant
      PS1, compared with ECL2 neurons in PP-lesioned PS1HWT mice. Finally, and in
      contrast to studies in nontransgenic mice and in mice expressing PS1HWT, ECL2
      neurons that express mutant PS1 and the calcium binding protein calbindin-D28k in
      ECL2 are also susceptible to lesion-induced neuronal loss. We conclude that
      expression of FAD-linked mutant PS1 variants enhances the vulnerability of
      neurons in the entorhinal cortex to PP lesion-induced cytotoxicity.

PMID- 16407540
TI  - Parietal cortex mediates voluntary control of spatial and nonspatial auditory
      attention.
AB  - The human posterior parietal cortex (PPC) is widely believed to subserve visually
      guided spatial behavior, including the control of visual attention, eye
      movements, and reaching. To explore the generality of this function, we measured
      human brain activity using functional magnetic resonance imaging during spatial
      and nonspatial shifts of auditory attention. Both spatial and nonspatial shifts
      of auditory attention evoked transient activity in the medial superior parietal
      cortex. These results reveal that the PPC is not exclusively devoted to
      visuospatial behavior; similar regions within a dorsomedial subcompartment
      provide a domain-independent reconfiguration signal for the control of spatial
      and nonspatial attention in both visual and nonvisual modalities.

PMID- 16407541
TI  - Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death
      through modulation of the transcription factor myocyte enhancer factor 2.
AB  - The mechanisms underlying dopamine neuron loss in Parkinson's disease (PD) are
      not clearly defined. Here, we delineate a pathway by which dopaminergic loss
      induced by 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) is controlled in
      vivo. We reported previously that calpains play a central required role in
      dopamine loss after MPTP treatment. Here, we provide evidence that the downstream
      effector pathway of calpains is through cyclin-dependent kinase 5 (cdk5)-mediated
      modulation of the transcription factor myocyte enhancer factor 2 (MEF2). We show
      that MPTP-induced conversion of the cdk5 activator p35 to a pathogenic p25 form
      is dependent on calpain activity in vivo. In addition, p35 deficiency attenuates
      MPTP-induced dopamine neuron loss and behavioral outcome. Moreover, MEF2 is
      phosphorylated on Ser444, an inactivating site, after MPTP treatment. This
      phosphorylation is dependent on both calpain and p35 activity, consistent with
      the model that calpain-mediated activation of cdk5 results in phosphorylation of
      MEF2 in vivo. Finally, we provide evidence that MEF2 is critical for dopaminergic
      loss because "cdk5 phosphorylation site mutant" of MEF2D provides neuroprotection
      in an MPTP mouse model of PD. Together, these data indicate that calpain-p35
      p25/cdk5-mediated inactivation of MEF2 plays a critical role in dopaminergic loss
      in vivo.

PMID- 16407542
TI  - Balanced excitation and inhibition determine spike timing during frequency
      adaptation.
AB  - In layer 4 (L4) of the rat barrel cortex, a single whisker deflection evokes a
      stereotyped sequence of excitation followed by inhibition, hypothesized to result
      in a narrow temporal window for spike output. However, awake rats sweep their
      whiskers across objects, activating the cortex at frequencies known to induce
      short-term depression at both excitatory and inhibitory synapses within L4.
      Although periodic whisker deflection causes a frequency-dependent reduction of
      the cortical response magnitude, whether this adaptation involves changes in the
      relative balance of excitation and inhibition and how these changes might impact
      the proposed narrow window of spike timing in L4 is unknown. Here, we demonstrate
      for the first time that spike output in L4 is determined precisely by the dynamic
      interaction of excitatory and inhibitory conductances. Furthermore, we show that
      periodic whisker deflection results in balanced adaptation of the magnitude and
      timing of excitatory and inhibitory input to L4 neurons. This balanced adaptation
      mediates a reduction in spike output while preserving the narrow time window of
      spike generation, suggesting that L4 circuits are calibrated to maintain relative
      levels of excitation and inhibition across varying magnitudes of input.

PMID- 16407543
TI  - Transcranial magnetic stimulation of frontal oculomotor regions during smooth
      pursuit.
AB  - Both the frontal eye fields (FEFs) and supplementary eye fields (SEFs) are known
      to be involved in smooth pursuit eye movements. It has been shown recently that
      stimulation of the smooth-pursuit area of the FEF [frontal pursuit area (FPA)] in
      monkey increases the pursuit response to unexpected changes in target motion
      during pursuit. In the current study, we applied transcranial magnetic
      stimulation (TMS) to the FPA and SEF in humans during sinusoidal pursuit to
      assess its effects on the pursuit response to predictable, rather than
      unexpected, changes in target motion. For the FPA, we found that TMS applied
      immediately before the target reversed direction increased eye velocity in the
      new direction, whereas TMS applied in mid-cycle, immediately before the target
      began to slow, decreased eye velocity. For the SEF, TMS applied at target
      reversal increased eye velocity in the new direction but had no effect on eye
      velocity when applied at mid-cycle. TMS of the control region (leg region of the
      somatosensory cortex) did not affect eye velocity at either point. Previous
      stimulation studies of FPA during pursuit have suggested that this region is
      involved in controlling the gain of the transformation of visual signals into
      pursuit motor commands. The current results suggest that the gain of the
      transformation of predictive signals into motor commands is also controlled by
      the FPA. The effect of stimulation of the SEF is distinct from that of the FPA
      and suggests that its role in sinusoidal pursuit is primarily at the target
      direction reversal.

PMID- 16407544
TI  - Compensatory changes in the noradrenergic nervous system in the locus ceruleus
      and hippocampus of postmortem subjects with Alzheimer's disease and dementia with
      Lewy bodies.
AB  - In Alzheimer's disease (AD), there is a significant loss of locus ceruleus (LC)
      noradrenergic neurons. However, functional and anatomical evidence indicates that
      the remaining noradrenergic neurons may be compensating for the loss. Because the
      noradrenergic system plays an important role in learning and memory, it is
      important to determine whether compensation occurs in noradrenergic neurons in
      the LC and hippocampus of subjects with AD or a related dementing disorder,
      dementia with Lewy bodies (DLB). We observed profound neuronal loss in the LC in
      AD and DLB subjects with three major changes in the noradrenergic system
      consistent with compensation: (1) an increase in tyrosine hydroxylase (TH) mRNA
      expression in the remaining neurons; (2) sprouting of dendrites into peri-LC
      dendritic zone, as determined by alpha2-adrenoreceptors (ARs) and norepinephrine
      transporter binding sites; and (3) sprouting of axonal projections to the
      hippocampus as determined by alpha2-ARs. In AD and DLB subjects, the postsynaptic
      alpha1-ARs were normal to elevated. Expression of alpha1A- and alpha2A-AR mRNA in
      the hippocampus of AD and DLB subjects were not altered, but expression of
      alpha1D- and alpha2C-AR mRNA was significantly reduced in the hippocampus of AD
      and DLB subjects. Therefore, in AD and DLB subjects, there is compensation
      occurring in the remaining noradrenergic neurons, but there does appear to be a
      loss of specific AR in the hippocampus. Because changes in these noradrenergic
      markers in AD versus DLB subjects were similar (except neuronal loss and the
      increase in TH mRNA were somewhat greater in DLB subjects), the presence of Lewy
      bodies in addition to plaques and tangles in DLB subjects does not appear to
      further affect the noradrenergic compensatory changes.

PMID- 16407546
TI  - Tactile spatial attention enhances gamma-band activity in somatosensory cortex
      and reduces low-frequency activity in parieto-occipital areas.
AB  - We investigated the effects of spatial-selective attention on oscillatory
      neuronal dynamics in a tactile delayed-match-to-sample task. Whole-head
      magnetoencephalography was recorded in healthy subjects while dot patterns were
      presented to their index fingers using Braille stimulators. The subjects' task
      was to report the reoccurrence of an initially presented sample pattern in a
      series of up to eight test stimuli that were presented unpredictably to their
      right or left index finger. Attention was cued to one side (finger) at the
      beginning of each trial, and subjects performed the task at the attended side,
      ignoring the unattended side. After stimulation, high-frequency gamma-band
      activity (60-95 Hz) in presumed primary somatosensory cortex (S1) was enhanced,
      whereas alpha- and beta-band activity were suppressed in somatosensory and
      occipital areas and then rebounded. Interestingly, despite the absence of any
      visual stimulation, we also found time-locked activation of medial occipital,
      presumably visual, cortex. Most relevant, spatial tactile attention enhanced
      stimulus-induced gamma-band activity in brain regions consistent with
      contralateral S1 and deepened and prolonged the stimulus induced suppression of
      beta- and alpha-band activity, maximal in parieto-occipital cortex. Additionally,
      the beta rebound over contralateral sensorimotor areas was suppressed. We
      hypothesize that spatial-selective attention enhances the saliency of sensory
      representations by synchronizing neuronal responses in early somatosensory cortex
      and thereby enhancing their impact on downstream areas and facilitating
      interareal processing. Furthermore, processing of tactile patterns also seems to
      recruit visual cortex and this even more so for attended compared with unattended
      stimuli.

PMID- 16407547
TI  - The continuous wagon wheel illusion is associated with changes in
      electroencephalogram power at approximately 13 Hz.
AB  - Continuously moving objects sometimes appear to spontaneously reverse their
      motion direction. The mechanisms underlying this bistable phenomenon (the
      "continuous wagon wheel illusion") are heavily debated, but one interpretation
      suggests that motion information is perceived in discrete episodes at a rate
      between 10 and 15 Hz. Here, we asked observers to report the perceived direction
      of a continuously rotating wheel while 32-channel electroencephalogram (EEG) was
      recorded. We then separated periods of perceived true from illusory (reversed)
      motion and compared the EEG power spectrum under these two perceptually distinct
      yet physically identical conditions. The only reliable difference was observed
      approximately 13 Hz over centroparietal electrodes, independent of the temporal
      frequency of the wheel. Thus, it is likely to reflect internal processes rather
      than purely stimulus-driven activity. EEG power (13 Hz) decreased before the
      onset of illusory motion and increased before transitions back to real motion.
      Using this relationship, it was possible to predict above chance, on a trial-by
      trial basis, the direction of the upcoming perceptual transition. These data are
      compatible with the idea that motion perception occurs in snapshots <100 ms in
      duration.

PMID- 16407545
TI  - Electrical hyperexcitation of lateral ventral pacemaker neurons desynchronizes
      downstream circadian oscillators in the fly circadian circuit and induces
      multiple behavioral periods.
AB  - Coupling of autonomous cellular oscillators is an essential aspect of circadian
      clock function but little is known about its circuit requirements. Functional
      ablation of the pigment-dispersing factor-expressing lateral ventral subset (LNV)
      of Drosophila clock neurons abolishes circadian rhythms of locomotor activity.
      The hypothesis that LNVs synchronize oscillations in downstream clock neurons was
      tested by rendering the LNVs hyperexcitable via transgenic expression of a low
      activation threshold voltage-gated sodium channel. When the LNVs are made
      hyperexcitable, free-running behavioral rhythms decompose into multiple
      independent superimposed oscillations and the clock protein oscillations in the
      dorsal neuron 1 and 2 subgroups of clock neurons are phase-shifted. Thus,
      regulated electrical activity of the LNVs synchronize multiple oscillators in the
      fly circadian pacemaker circuit.

PMID- 16407548
TI  - Glypican-1 and alpha4(V) collagen are required for Schwann cell myelination.
AB  - Schwann cell myelination requires interactions with the extracellular matrix
      (ECM) mediated by cell surface receptors. Previously, we identified a type V
      collagen family member, alpha4(V) collagen, which is expressed by Schwann cells
      during peripheral nerve differentiation. This collagen binds with high affinity
      to heparan sulfate through a unique binding motif in the noncollagenous N
      terminal domain (NTD). The principal alpha4(V) collagen-binding protein on the
      Schwann cell surface is the heparan sulfate proteoglycan glypican-1. We
      investigated the role of alpha4(V) collagen and glypican-1 in Schwann cell
      terminal differentiation in cultures of Schwann cells and dorsal root ganglion
      neurons. Small interfering RNA-mediated suppression of glypican-1 expression
      decreased binding of alpha4(V)-NTD to Schwann cells, adhesion and spreading of
      Schwann cells on alpha4(V)-NTD, and incorporation of alpha4(V) collagen into
      Schwann cell ECM. In cocultures, alpha4(V) collagen coassembles with laminin on
      the surface of polarized Schwann cells to form tube-like ECM structures that are
      sites of myelination. Suppression of glypican-1 or alpha4(V) collagen expression
      significantly inhibited myelination. These results demonstrate an important role
      for these proteins in peripheral nerve terminal differentiation.

PMID- 16407549
TI  - Peptidomics of a single identified neuron reveals diversity of multiple
      neuropeptides with convergent actions on cellular excitability.
AB  - In contrast to classical transmitters, the detailed structures and cellular and
      synaptic actions of neuropeptides are less well described. Peptide mass profiling
      of single identified neurons of the mollusc Lymnaea stagnalis indicated the
      presence of 17 abundant neuropeptides in the cardiorespiratory neuron, visceral
      dorsal 1 (VD1), and a subset of 14 peptides in its electrically coupled
      counterpart, right parietal dorsal 2. Altogether, based on this and previous
      work, we showed that the high number of peptides arises from the expression and
      processing of four distinct peptide precursor proteins, including a novel one.
      Second, we established a variety of posttranslational modifications of the
      generated peptides, including phosphorylation, disulphide linkage, glycosylation,
      hydroxylation, N-terminal pyroglutamylation, and C-terminal amidation. Specific
      synapses between VD1 and its muscle targets were formed, and their synaptic
      physiology was investigated. Whole-cell voltage-clamp analysis of dissociated
      heart muscle cells revealed, as tested for a selection of representative family
      members and their modifications, that the peptides of VD1 exhibit convergent
      activation of a high-voltage-activated Ca current. Moreover, the differentially
      glycosylated and hydroxylated alpha2 peptides were more potent than the
      unmodified alpha2 peptide in enhancing these currents. Together, this study is
      the first to demonstrate that single neurons exhibit such a complex pattern of
      peptide gene expression, precursor processing, and differential peptide
      modifications along with a remarkable degree of convergence of neuromodulatory
      actions. This study thus underscores the importance of a detailed mass
      spectrometric analysis of neuronal peptide content and peptide modifications
      related to neuromodulatory function.

PMID- 16407550
TI  - Late developmental stage-specific role of tryptophan hydroxylase 1 in brain
      serotonin levels.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] is a major therapeutic target of
      psychiatric disorders. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting
      reaction in the biosynthesis of 5-HT. Two isoforms (TPH1 and TPH2) having
      tryptophan hydroxylating activity were identified. Association studies have
      revealed possible TPH1 involvement in psychiatric conditions and behavioral
      traits. However, TPH1 mRNA was reported to be mainly expressed in the pineal
      gland and the periphery and to be barely detected in the brain. Therefore,
      contribution of TPH1 to brain 5-HT levels is not known, and the mechanisms how
      TPH1 possibly contributes to the pathogenesis of psychiatric disorders are not
      understood. Here, we show an unexpected role of TPH1 in the developing brain. We
      found that TPH1 is expressed preferentially during the late developmental stage
      in the mouse brain. TPH1 showed higher affinity to tryptophan and stronger enzyme
      activity than TPH2 in a condition reflecting that of the developing brainstem.
      Low 5-HT contents in the raphe nucleus were seen during development in New
      Zealand white (NZW) and SWR mice having common functional polymorphisms in the
      TPH1 gene. However, the 5-HT contents in these mice were not reduced in
      adulthood. In adult NZW and SWR mice, depression-related behavior was observed.
      Considering an involvement of developmental brain disturbance in psychiatric
      disorders, TPH1 may act specifically on development of 5-HT neurons, and thereby
      influence behavior later in life.

PMID- 16407551
TI  - Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine model of Parkinson's disease.
AB  - Epidemiological studies have strongly linked caffeine consumption with a reduced
      risk of developing Parkinson's disease (PD) in men. Interestingly, in women, this
      inverse association is present only in those who have not taken postmenopausal
      estrogens, suggesting an interaction between the influences of estrogen and
      caffeine use on the risk of PD. To explore a possible biological basis for this
      interaction, we systematically investigated how the neuroprotective effect of
      caffeine is influenced by gender, ovariectomy (OVX), and then exogenous estrogen
      in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. (1)
      Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal
      dopamine loss in both young and retired breeder (RB) male, but not female, mice.
      (2) In female mice (both young and RB), caffeine was less potent or altogether
      ineffective as a neuroprotectant after sham surgery compared to OVX or after OVX
      plus estrogen replacement compared to OVX plus placebo treatment. (3) Estrogen
      treatment also prevented the protection of caffeine against dopamine loss in
      young male mice. (4) Consistent with the putative protective effect of estrogen,
      female and OVX plus estrogen mice were relatively resistant to MPTP toxicity
      compared to male and OVX plus placebo mice, respectively. (5) There was no
      overall difference in brain levels of caffeine and its metabolites between OVX
      plus placebo and OVX plus estrogen mice. Together, these results suggest that
      estrogen can occlude and thereby prevent the neuroprotective effect of caffeine
      in a model of PD neurodegeneration, supporting a biological basis for the
      interaction between estrogen and caffeine in modifying the risk of PD.

PMID- 16407552
TI  - Alix, making a link between apoptosis-linked gene-2, the endosomal sorting
      complexes required for transport, and neuronal death in vivo.
AB  - Alix/apoptosis-linked gene-2 (ALG-2)-interacting protein X is an adaptor protein
      involved in the regulation of the endolysosomal system through binding to
      endophilins and to endosomal sorting complexes required for transport (ESCRT)
      proteins, TSG101 and CHMP4b. It was first characterized as an interactor of ALG
      2, a calcium-binding protein necessary for cell death, and several observations
      suggest a role for Alix in controlling cell death. We used electroporation in the
      chick embryo to test whether overexpressed wild-type or mutated Alix proteins
      influence cell death in vivo. We show that Alix overexpression is sufficient to
      induce cell death of neuroepithelial cells. This effect is strictly dependent on
      its capacity to bind to ALG-2. On the other hand, expression of Alix mutants
      lacking the ALG-2 or the CHMP4b binding sites prevents early programmed cell
      death in cervical motoneurons at day 4.5 of chick embryo development. This
      protection afforded by Alix mutants was abolished after deletion of the TSG101,
      but not of the endophilin, binding sites. Our results suggest that the
      interaction of the ALG-2/Alix complex with ESCRT proteins is necessary for
      naturally occurring death of motoneurons. Therefore, Alix represents a molecular
      link between the endolysosomal system and the cell death machinery.

PMID- 16407553
TI  - Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell
      formation during the development of the organ of Corti.
AB  - The basic helix-loop-helix (bHLH) transcription factor Math1 (also called Atoh1)
      is both necessary and sufficient for hair cell development in the mammalian
      cochlea (Bermingham et al., 1999; Zheng and Gao, 2000). Previous studies have
      demonstrated that a dynamic pattern of Math1 expression plays a key role in
      regulating the number and position of mechanosensory hair cells. However, the
      factors that regulate the temporal and spatial expression of Math1 within the
      cochlea are unknown. The bHLH-related inhibitors of differentiation and DNA
      binding (Id) proteins are known to negatively regulate many bHLH transcription
      factors, including Math1, in a number of different systems. Therefore, Id
      proteins are good candidates for regulating Math1 in the cochlea. Results from
      PCR and in situ hybridization indicate that Id1, Id2, and Id3 are expressed
      within the cochlear duct in a pattern that is consistent with a role in
      regulation of hair cell development. In particular, expression of Ids and Math1
      overlapped in cochlear progenitor cells before cellular differentiation, but a
      specific downregulation of Id expression was observed in individual cells that
      differentiated as hair cells. In addition, progenitor cells in which the
      expression of Ids was maintained during the time period for hair cell
      differentiation were inhibited from developing as hair cells. These results
      indicate a key role for Ids in the regulation of expression of Math1 and hair
      cell differentiation in the developing cochlea.

PMID- 16407554
TI  - Placebo-induced changes in spinal cord pain processing.
AB  - Pain is an essential sensory modality, signaling injury or threat of injury. Pain
      perception depends on both biological and psychological factors. However, it is
      not known whether psychological factors modify spinal mechanisms or if its effect
      is limited to cortical processing. Here, we use a placebo analgesic model to show
      that psychological factors affect human spinal nociceptive processes. Mechanical
      hyperalgesia (hypersensitivity) after an injury is attributable to sensitized
      sensory neurons in the spinal cord. After a 5 min, 46 degrees C heating of the
      skin, subjects developed areas of mechanical hyperalgesia. This area was smaller
      in a placebo condition compared with a baseline condition. This result suggests
      that placebo analgesia affects the spinal cord as well as supra-spinal pain
      mechanisms in humans and provides strong supporting evidence that placebo
      analgesia is not simply altered reporting behavior. Central sensitization is
      thought to mediate the exaggerated pain after innocuous sensory stimulation in
      several clinical pain conditions that follow trauma and nervous-system injury.
      These new data indicate that expectation about pain and analgesia is an important
      component of the cognitive control of central sensitization.

PMID- 16407555
TI  - Foveal visual strategy during self-motion is independent of spatial attention.
AB  - Translational self-motion disturbs the stability of retinal images by inducing a
      pattern of retinal optic flow that cannot be compensated globally by a single eye
      movement. The eyes must rotate by different amounts, depending on which spatial
      location needs to be stabilized on the retina. However, compensatory eye
      movements during steady fixation are always such as to maintain visual acuity on
      the fovea at the expense of significant image slip on the peripheral retina. We
      investigated whether such a foveal visual strategy during translation is hard
      wired or whether it embeds enough flexibility to also allow for behaviorally
      relevant objects outside the foveae to be stabilized preferentially on the
      retinas. Monkeys were moved forward or backward and leftward or rightward
      passively in darkness while planning a saccade or bar release to peripheral
      dimmed targets. By comparing the eye movements made during these tasks with those
      under conditions of steady fixation, we found that the motion-induced eye
      movements depended only on current fixation. This was true even during the last
      milliseconds just before a saccade to the peripheral target. We conclude that the
      foveal stabilization strategy is invariant and solely dependent on current eye
      position, a strategy that is optimal for both processing speed and efficiency in
      the extraction of heading information from retinal flow during self-motion.

PMID- 16407556
TI  - Functional dissection of a neuronal network required for cuticle tanning and wing
      expansion in Drosophila.
AB  - A subset of Drosophila neurons that expresses crustacean cardioactive peptide
      (CCAP) has been shown previously to make the hormone bursicon, which is required
      for cuticle tanning and wing expansion after eclosion. Here we present evidence
      that CCAP-expressing neurons (NCCAP) consist of two functionally distinct groups,
      one of which releases bursicon into the hemolymph and the other of which
      regulates its release. The first group, which we call NCCAP-c929, includes 14
      bursicon-expressing neurons of the abdominal ganglion that lie within the
      expression pattern of the enhancer-trap line c929-Gal4. We show that suppression
      of activity within this group blocks bursicon release into the hemolymph together
      with tanning and wing expansion. The second group, which we call NCCAP-R,
      consists of NCCAP neurons outside the c929-Gal4 pattern. Because suppression of
      synaptic transmission and protein kinase A (PKA) activity throughout NCCAP, but
      not in NCCAP-c929, also blocks tanning and wing expansion, we conclude that
      neurotransmission and PKA are required in NCCAP-R to regulate bursicon secretion
      from NCCAP-c929. Enhancement of electrical activity in NCCAP-R by expression of
      the bacterial sodium channel NaChBac also blocks tanning and wing expansion and
      leads to depletion of bursicon from central processes. NaChBac expression in
      NCCAP-c929 is without effect, suggesting that the abdominal bursicon-secreting
      neurons are likely to be silent until stimulated to release the hormone. Our
      results suggest that NCCAP form an interacting neuronal network responsible for
      the regulation and release of bursicon and suggest a model in which PKA-mediated
      stimulation of inputs to normally quiescent bursicon-expressing neurons activates
      release of the hormone.

PMID- 16407557
TI  - Single transmembrane domain insulin-like growth factor-II/mannose-6-phosphate
      receptor regulates central cholinergic function by activating a G-protein
      sensitive, protein kinase C-dependent pathway.
AB  - The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a
      single-pass transmembrane glycoprotein that plays an important role in the
      intracellular trafficking of lysosomal enzymes and endocytosis-mediated
      degradation of IGF-II. However, its role in signal transduction after IGF-II
      binding remains unclear. In the present study, we report that IGF-II/M6P receptor
      in the rat brain is coupled to a G-protein and that its activation by Leu27IGF
      II, an analog that binds rather selectively to the IGF-II/M6P receptor,
      potentiates endogenous acetylcholine release from the rat hippocampal formation.
      This effect is mediated by a pertussis toxin (PTX)-sensitive GTP-binding protein
      and is dependent on protein kinase Calpha (PKCalpha)-induced phosphorylation of
      downstream substrates, myristoylated alanine-rich C kinase substrate, and growth
      associated protein-43. Additionally, treatment with Leu27IGF-II causes a
      reduction in whole-cell currents and depolarization of cholinergic basal
      forebrain neurons. This effect, which is blocked by an antibody against the IGF
      II/M6P receptor, is also sensitive to PTX and is mediated via activation of a PKC
      dependent pathway. These results together revealed for the first time that the
      single transmembrane domain IGF-II/M6P receptor expressed in the brain is G
      protein coupled and is involved in the regulation of central cholinergic function
      via the activation of specific intracellular signaling cascades.

PMID- 16407558
TI  - GABAergic signaling at mossy fiber synapses in neonatal rat hippocampus.
AB  - In the adult rat hippocampus, granule cell mossy fibers (MFs) form excitatory
      glutamatergic synapses with CA3 principal cells and local inhibitory
      interneurons. However, evidence has been provided that, in young animals and
      after seizures, the same fibers can release in addition to glutamate GABA. Here
      we show that, during the first postnatal week, stimulation of granule cells in
      the dentate gyrus gave rise to monosynaptic GABAA-mediated responses in principal
      cells and in interneurons. These synapses were indeed made by MFs because they
      exhibited strong paired-pulse facilitation, high sensitivity to the metabotropic
      glutamate receptor agonist l-AP-4, and short-term frequency-dependent
      facilitation. MF responses were potentiated by blocking the plasma membrane GABA
      transporter GAT-1 with NO-711 or by allosterically modulating GABAA receptors
      with flurazepam. Chemical stimulation of granule cell dendrites with glutamate
      induced barrages of GABAA-mediated postsynaptic currents into target neurons.
      Furthermore, immunocytochemical experiments demonstrated colocalization of
      vesicular GABA transporter with vesicular glutamate transporter-1 and zinc
      transporter 3, suggesting that GABA can be taken up and stored in synaptic
      vesicles of MF terminals. Additional fibers releasing both glutamate and GABA
      into principal cells and interneurons were recruited by increasing the strength
      of stimulation. Both the GABAergic and the glutamatergic component of synaptic
      currents occurred with the same latency and were reversibly abolished by l-AP-4,
      indicating that they originated from the MFs. GABAergic signaling may play a
      crucial role in tuning hippocampal network during postnatal development. Low
      threshold GABA-releasing fibers may undergo elimination, and this may occur when
      GABA shifts from the depolarizing to the hyperpolarizing direction.

PMID- 16407559
TI  - Neurogenesis in the caudate nucleus of the adult rabbit.
AB  - Stem cells with the potential to give rise to new neurons reside in different
      regions of the adult rodents CNS, but in vivo only the hippocampal dentate gyrus
      and the subventricular zone-olfactory bulb system are neurogenic under
      physiological condition. Comparative analyses have shown that vast species
      differences exist in the way the mammalian brain is organized and in its
      neurogenic capacity. Accordingly, we have demonstrated recently that, in the
      adult rabbit brain, striking structural plasticity persists in several cortical
      and subcortical areas. Here, by using markers for immature and mature neuronal
      and glial cell types, endogenous and exogenously administered cell-proliferation
      markers, intraventricular cell tracer injections coupled to confocal analysis,
      three-dimensional reconstructions, and in vitro tissue cultures, we demonstrate
      the existence of newly formed neurons in the caudate nucleus of normal,
      untreated, adult rabbit. Our results suggest that neurogenesis in the caudate
      nucleus is a phenomenon independent from that occurring in the adjacent
      subventricular zone, mostly attributable to the activity of clusters of
      proliferating cells located within the parenchyma of this nucleus. These clusters
      originate chains of neuroblasts that ultimately differentiate into mature
      neurons, which represent only a small percentage of the total neuronal
      precursors. These results indicate that striatum of rabbit represents a favorable
      environment for genesis rather than survival of newly formed neurons.

PMID- 16407561
TI  - Different effects on fast exocytosis induced by synaptotagmin 1 and 2 isoforms
      and abundance but not by phosphorylation.
AB  - Synaptotagmins comprise a large protein family, of which synaptotagmin 1 (Syt1)
      is a Ca2+ sensor for fast exocytosis, and its close relative, synaptotagmin 2
      (Syt2), is assumed to serve similar functions. Chromaffin cells express Syt1 but
      not Syt2. We compared secretion from chromaffin cells from Syt1 null mice
      overexpressing either Syt isoform. High time-resolution capacitance measurement
      showed that Syt1 null cells lack the exocytotic phase corresponding to the
      readily-releasable pool (RRP) of vesicles. Comparison with the amperometric
      signal confirmed that the missing phase of exocytosis consists of catecholamine
      containing vesicles. Overexpression of Syt1 rescued the RRP and increased its
      size above wild-type values, whereas the size of the slowly releasable pool
      decreased, indicating that the availability of Syt1 regulates the relative size
      of the two releasable pools. The RRP was also rescued by Syt2 overexpression, but
      the kinetics of fusion was slightly slower than in cells expressing Syt1.
      Biochemical experiments showed that Syt2 has a slightly lower Ca2+ affinity for
      phospholipid binding than Syt1 because of a difference in the C2A domain. These
      data constitute evidence for the function of Syt1 and Syt2 as alternative, but
      not identical, calcium-sensors for RRP fusion. By overexpression of Syt1 mutated
      in the shared PKC/calcium/calmodulin-dependent kinase phosphorylation site, we
      show that phorbol esters act independently and upstream of Syt1 to regulate the
      size of the releasable pools. We conclude that exocytosis from mouse chromaffin
      cells can be modified by the differential expression of Syt isoforms and by Syt
      abundance but not by phosphorylation of Syt1.

PMID- 16407560
TI  - Head direction cell representations maintain internal coherence during
      conflicting proximal and distal cue rotations: comparison with hippocampal place
      cells.
AB  - Place cells of the hippocampal formation encode a spatial representation of the
      environment, and the orientation of this representation is apparently governed by
      the head direction cell system. The representation of a well explored environment
      by CA1 place cells can be split when there is conflicting information from
      salient proximal and distal cues, because some place fields rotate to follow the
      distal cues, whereas others rotate to follow the proximal cues (Knierim, 2002a).
      In contrast, the CA3 representation is more coherent than CA1, because the place
      fields in CA3 tend to rotate in the same direction (Lee et al., 2004). The
      present study tests whether the head direction cell network produces a split
      representation or remains coherent under these conditions by simultaneously
      recording both CA1 place cells and head direction cells from the thalamus. In
      agreement with previous studies, split representations of the environment were
      observed in ensembles of CA1 place cells in approximately 75% of the mismatch
      sessions, in which some fields followed the counterclockwise rotation of proximal
      cues and other fields followed the clockwise rotation of distal cues. However, of
      225 recording sessions, there was not a single instance of the head direction
      cell ensembles revealing a split representation of head direction. Instead, in
      most of the mismatch sessions, the head direction cell tuning curves rotated as
      an ensemble clockwise (94%) and in a few sessions rotated counterclockwise (6%).
      The findings support the notion that the head direction cells may be part of an
      attractor network bound more strongly to distal landmarks than proximal
      landmarks, even under conditions in which the CA1 place representation loses its
      coherence.

PMID- 16407562
TI  - Impaired glutamate transport in a mouse model of tau pathology in astrocytes.
AB  - Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of
      tauopathies. The discovery of microtubule-associated protein tau gene mutations
      that are pathogenic for a heterogenous group of neurodegenerative disorders,
      called frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP
      17), directly implicate tau abnormalities in the onset/progression of disease.
      Although the role of tau pathology in neurons in disease pathogenesis is well
      accepted, the contribution of glial pathology is essentially unknown. We recently
      generated a transgenic (Tg) mouse model of tau pathology in astrocytes by
      expressing the human tau protein under the control of the glial fibrillary acidic
      protein (GFAP) promoter. Both wild-type and FTDP-17 mutant GFAP/tau Tg animals
      manifest an age-dependent accumulation of tau inclusions in astrocytes that
      resembles the pathology observed in human tauopathies. We further demonstrate
      that both strains of Tg mice manifest compromised motor function that correlates
      with altered expression of the glial glutamate-aspartate transporter and occurs
      before the development of tau pathology. Subsequently, the Tg mice manifest
      additional deficits in neuromuscular strength that correlates with reduced
      expression of glutamate transporter-1 (GLT-1) and occurs concurrent with tau
      inclusion pathology. Reduced GLT-1 expression was associated with a progressive
      decrease in sodium-dependent glutamate transport capacity. Reductions in GLT-1
      expression were also observed in corticobasal degeneration, a tauopathy with
      prominent pathology in astrocytes. Less robust changes were observed in
      Alzheimer's disease in which neuronal tau pathology predominates. Thus, these Tg
      mice recapitulate features of astrocytic pathology observed in tauopathies and
      implicate a role for altered astrocyte function in the pathogenesis of these
      disorders.

PMID- 16407563
TI  - Neuromuscular synapse formation in mice lacking motor neuron- and skeletal muscle
      derived Neuregulin-1.
AB  - The localization of acetylcholine receptors (AChRs) to the vertebrate
      neuromuscular junction is mediated, in part, through selective transcription of
      AChR subunit genes in myofiber subsynaptic nuclei. Agrin and the muscle-specific
      receptor tyrosine kinase, MuSK, have critical roles in synapse-specific
      transcription, because AChR genes are expressed uniformly in mice lacking either
      agrin or MuSK. Several lines of evidence suggest that agrin and MuSK stimulate
      synapse-specific transcription indirectly by regulating the distribution of other
      cell surface ligands, which stimulate a pathway for synapse-specific gene
      expression. This putative secondary signal for directing AChR gene expression to
      synapses is not known, but Neuregulin-1 (Nrg-1), primarily based on its presence
      at synapses and its ability to induce AChR gene expression in vitro, has been
      considered a good candidate. To study the role of Nrg-1 at neuromuscular
      synapses, we inactivated nrg-1 in motor neurons, skeletal muscle, or both cell
      types, using mice that express Cre recombinase selectively in developing motor
      neurons or in developing skeletal myofibers. We find that AChRs are clustered at
      synapses and that synapse-specific transcription is normal in mice lacking Nrg-1
      in motor neurons, myofibers, or both cell types. These data indicate that Nrg-1
      is dispensable for clustering AChRs and activating AChR genes in subsynaptic
      nuclei during development and suggest that these aspects of postsynaptic
      differentiation are dependent on Agrin/MuSK signaling without a requirement for a
      secondary signal.

PMID- 16407564
TI  - Glia as a therapeutic target: selective suppression of human amyloid-beta-induced
      upregulation of brain proinflammatory cytokine production attenuates
      neurodegeneration.
AB  - A corollary of the neuroinflammation hypothesis is that selective suppression of
      neurotoxic products produced by excessive glial activation will result in
      neuroprotection. We report here that daily oral administration to mice of the
      brain-penetrant compound 4,6-diphenyl-3-(4-(pyrimidin-2-yl)piperazin-1
      yl)pyridazine (MW01-5-188WH), a selective inhibitor of proinflammatory cytokine
      production by activated glia, suppressed the human amyloid-beta (Abeta) 1-42
      induced upregulation of interleukin-1beta, tumor necrosis factor-alpha, and S100B
      in the hippocampus. Suppression of neuroinflammation was accompanied by
      restoration of hippocampal synaptic dysfunction markers synaptophysin and
      postsynaptic density-95 back toward control levels. Consistent with the
      neuropathophysiological improvements, MW01-5-188WH therapy attenuated deficits in
      Y maze behavior, a hippocampal-linked task. Oral MW01-5-188WH therapy begun 3
      weeks after initiation of intracerebroventricular infusion of human Abeta
      decreased the numbers of activated astrocytes and microglia and the cytokine
      levels in the hippocampus without modifying amyloid plaque burden or altering
      peripheral tissue cytokine upregulation in response to an in vivo inflammatory
      challenge. The results provide a novel integrative chemical biology proof in
      support of the neuroinflammation hypothesis of disease progression, demonstrate
      that neurodegeneration can be attenuated independently of plaque modulation by
      targeting innate brain proinflammatory cytokine responses, and indicate the
      feasibility of developing efficacious, safe, and selective therapies for
      neurodegenerative disorders by targeting key glial activation pathways.

PMID- 16407565
TI  - Sodium currents activate without a Hodgkin-and-Huxley-type delay in central
      mammalian neurons.
AB  - Hodgkin and Huxley established that sodium currents in the squid giant axons
      activate after a delay, which is explained by the model of a channel with three
      identical independent gates that all have to open before the channel can pass
      current (the HH model). It is assumed that this model can adequately describe the
      sodium current activation time course in all mammalian central neurons, although
      there is no experimental evidence to support such a conjecture. We performed high
      temporal resolution studies of sodium currents gating in three types of central
      neurons. The results show that, within the tested voltage range from -55 to -35
      mV, in all of these neurons, the activation time course of the current could be
      fit, after a brief delay, with a monoexponential function. The duration of delay
      from the start of the voltage command to the start of the extrapolated
      monoexponential fit was much smaller than predicted by the HH model. For example,
      in prefrontal cortex pyramidal neurons, at -46 mV and 12 degrees C, the observed
      average delay was 140 micros versus the 740 micros predicted by the two-gate HH
      model and the 1180 micros predicted by the three-gate HH model. These results can
      be explained by a model with two closed states and one open state. In this model,
      the transition between two closed states is approximately five times faster than
      the transition between the second closed state and the open state. This model
      captures all major properties of the sodium current activation. In addition, the
      proposed model reproduces the observed action potential shape more accurately
      than the traditional HH model.

PMID- 16407566
TI  - The Kv2.1 C terminus can autonomously transfer Kv2.1-like phosphorylation
      dependent localization, voltage-dependent gating, and muscarinic modulation to
      diverse Kv channels.
AB  - Modulation of K+ channels is widely used to dynamically regulate neuronal
      membrane excitability. The voltage-gated K+ channel Kv2.1 is an abundant delayed
      rectifier K+ (IK) channel expressed at high levels in many types of mammalian
      central neurons where it regulates diverse aspects of membrane excitability.
      Neuronal Kv2.1 is constitutively phosphorylated, localized in high-density
      somatodendritic clusters, and has a relatively depolarized voltage dependence of
      activation. Here, we show that the clustering and voltage-dependent gating of
      endogenous Kv2.1 in cultured rat hippocampal neurons are modulated by cholinergic
      stimulation, a common form of neuromodulation. The properties of neuronal Kv2.1
      are recapitulated in recombinant Kv2.1 expressed in human embryonic kidney 293
      (HEK293) cells, but not COS-1 cells, because of cell background-specific
      differences in Kv2.1 phosphorylation. As in neurons, Kv2.1 in HEK293 cells is
      dynamically regulated by cholinergic stimulation, which leads to Ca2+/calcineurin
      dependent dephosphorylation of Kv2.1, dispersion of channel clusters, and
      hyperpolarizing shifts in the voltage-dependent gating properties of the channel.
      Immunocytochemical, biochemical, and biophysical analyses of chimeric Kv channels
      show that the Kv2.1 cytoplasmic C-terminal domain can act as an autonomous domain
      sufficient to transfer Kv2.1-like clustering, voltage-dependent activation, and
      cholinergic modulation to diverse Kv channels. These findings provide novel
      mechanistic insights into cholinergic modulation of ion channels and regulation
      of the localization and voltage-dependent gating properties of the abundant
      neuronal Kv2.1 channel by cholinergic and other neuromodulatory stimuli.

PMID- 16407568
TI  - NMDA receptors in layer 4 spiny stellate cells of the mouse barrel cortex contain
      the NR2C subunit.
AB  - In layer 4 of the somatosensory cortex, the glutamatergic synapses that
      interconnect spiny stellate (SpS) neurons, which are the major targets of
      thalamocortical input, differ from most other neocortical excitatory synapses in
      that they have an extremely large NMDA receptor (NMDAR)-mediated component that
      is relatively insensitive to voltage-dependent Mg2+ blockade. We now report that
      this unique feature of the NMDA response reflects the distinctive subunit
      composition of the underlying receptors. We studied NMDAR-mediated miniature
      EPSCs (mEPSCs) and NMDA channel currents in tangential brain slices of mouse
      barrel cortex, which exclusively contain layer 4. NMDAR-mediated mEPSCs in SpS
      neurons were prominent at negative membrane potentials, and NMDA channels in
      outside-out patches excised from the somata of the same neurons had relatively
      low conductance and reduced susceptibility to Mg2+ block. These are
      characteristic features of heteromeric NMDAR assemblies that contain the NR2C
      subunit. Some patches also contained NMDA channels with higher conductance and a
      greater sensitivity to Mg2+. In the neocortex of transgenic mice in which a beta
      galactosidase (lacZ) indicator gene was controlled by the NR2C promoter, the lacZ
      indicator was densely expressed in layer 4. In current-clamp recordings, blockade
      of NMDARs caused hyperpolarization and an increase in apparent input resistance.
      Our data demonstrate that the SpS neurons of layer 4 functionally express NR2C
      subunits; this is the likely explanation for their ability to generate large
      NMDAR-mediated EPSPs that are effective at resting potential, without previous
      depolarization.

PMID- 16407569
TI  - Enhanced long-term potentiation-like plasticity of the trigeminal blink reflex
      circuit in blepharospasm.
AB  - Benign essential blepharospasm (BEB) is a focal cranial dystonia affecting eye
      closure. Here, we tested the hypothesis that BEB is associated with abnormal
      plasticity of the neuronal circuits mediating reflex blinks. In patients with BEB
      and healthy age-matched controls, we used the conditioning protocol introduced by
      Mao and Evinger (2001) to induce long-term potentiation (LTP)-like plasticity in
      trigeminal wide dynamic range neurons of the blink reflex circuit. High-frequency
      trains of electrical stimuli were repeatedly given over the right supraorbital
      nerve (SO) and timed to coincide with the R2 response elicited by a preceding SO
      stimulus. High-frequency stimulation (HFS) resulted in a long-lasting and input
      specific potentiation of the R2 response in both groups, yet the facilitation of
      the R2 response was markedly increased in patients relative to controls.
      Botulinum toxin (BTX) injections in both orbicularis oculi muscles normalized the
      previously enhanced LTP-like plasticity of the R2 response. The increased
      responsiveness to HFS provides first-time evidence that LTP-like plasticity is
      increased in the trigeminal reflex circuit of patients affected by BEB. The
      results also show that the enhanced modifiability is not fixed in BEB, because
      BTX injections can transiently restore normal LTP-like plasticity. We propose
      that an abnormal corneal input induced by excessive blinking exacerbates
      increased LTP-like plasticity in BEB. BTX treatment removes the latter and
      restores plasticity toward normal values. Our results support the concept that
      maladaptive reorganization contributes to the pathophysiology of focal dystonias.

PMID- 16407567
TI  - Modulation by brain natriuretic peptide of GABA receptors on rat retinal ON-type
      bipolar cells.
AB  - Natriuretic peptides (NPs) may work as neuromodulators through their associated
      receptors [NP receptors (NPRs)]. By immunocytochemistry, we showed that NPR-A and
      NPR-B were expressed abundantly on both ON-type and OFF-type bipolar cells (BCs)
      in rat retina, including the dendrites, somata, and axon terminals. Whole-cell
      recordings made from isolated ON-type BCs further showed that brain natriuretic
      peptide (BNP) suppressed GABAA receptor-, but not GABAC receptor-, mediated
      currents of the BCs, which was blocked by the NPR-A antagonist anantin. The NPR-C
      agonist c-ANF [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF(4-23)-NH2] did not
      suppress GABAA currents. The BNP effect on GABAA currents was abolished with
      preincubation with the pGC-A/B antagonist HS-142-1 but mimicked by application of
      8-bromoguanosine-3',5'-cyclomonophosphate. These results suggest that elevated
      levels of intracellular cGMP caused by activation of NPR-A may mediate the BNP
      effect. Internal infusion of the cGMP-dependent protein kinase G (PKG) inhibitor
      KT5823 essentially blocked the BNP-induced reduction of GABAA currents. Moreover,
      calcium imaging showed that BNP caused a significant elevation of intracellular
      calcium that could be caused by increased calcium release from intracellular
      stores by PKG. The BNP effect was blocked by the ryanodine receptor modulators
      caffeine, ryanodine, and ruthenium red but not by the IP3 receptor antagonists
      heparin and xestospongin-C. Furthermore, the BNP effect was abolished after
      application of the blocker of endoplasmic reticulum Ca2+-ATPase thapsigargin and
      greatly reduced by the calmodulin inhibitors W-7 and calmidazolium. We therefore
      conclude that the increased calcium release from ryanodine-sensitive calcium
      stores by BNP may be responsible for the BNP-caused GABAA response suppression in
      ON-type BCs through stimulating calmodulin.

PMID- 16407570
TI  - Temporally staggered glomerulus development in the moth Manduca sexta.
AB  - Glomeruli, neuropilar structures composed of olfactory receptor neuron (ORN) axon
      terminals and central neuron dendrites, are a common feature of olfactory
      systems. Typically, ORN axons segregate into glomeruli based on odor specificity,
      making glomeruli the basic unit for initial processing of odorant information.
      Developmentally, glomeruli arise from protoglomeruli, loose clusters of ORN axons
      that gradually synapse onto dendrites. Previous work in the moth Manduca sexta
      demonstrated that protoglomeruli develop in a wave across the antennal lobe (AL)
      during stage 5 of the 18 stages of metamorphic adult development. However, ORN
      axons from the distal segments of the antenna arrive at the AL for several more
      days. We report that protoglomeruli present at stage 5 account for only
      approximately two or three of adult glomeruli with the number of structures
      increasing over subsequent stages. How do these later arriving axons incorporate
      into glomeruli? Examining the dendritic projections of a unique serotonin
      containing neuron into glomeruli at later stages revealed glomeruli with immature
      dendritic arbors intermingled among more mature glomeruli. Labeling ORN axons
      that originate in proximal segments of the antenna suggested that early-arriving
      axons target a limited number of glomeruli. We conclude that AL glomeruli form
      over an extended time period, possibly as a result of ORNs expressing new odorant
      receptors arriving from distal antennal segments.

PMID- 16407571
TI  - Chain of command.

PMID- 16407572
TI  - Lessons from Drosophila models of DJ-1 deficiency.
AB  - Mutations in the DJ-1 gene are associated with rare forms of autosomal recessive
      early-onset Parkinson's disease (PD). Although the precise physiological function
      of DJ-1 remains obscure, accumulating evidence suggests that DJ-1 may normally
      function as a redox-sensitive molecular chaperone that can protect against the
      deleterious effects of oxidative stress, particularly in mitochondria. Recent
      studies in the fruit fly, Drosophila melanogaster, have shed further light on the
      biological role of DJ-1. DJ-1-deficient Drosophila models exhibit distinct
      phenotypes but collectively highlight a prominent neuroprotective role for DJ-1
      against oxidative insult. However, Drosophila lacking DJ-1 do not consistently
      produce a useful PD-like phenotype (that is, they generally fail to exhibit
      degeneration of neurons that contain the neurotransmitter dopamine), which may
      reflect putative compensatory neuroprotective mechanisms. DJ-1-deficient fly
      models further highlight the utility of Drosophila as an important tool for
      elucidating protein function and for modeling neurodegenerative disease.

PMID- 16407573
TI  - Heart disease and stroke statistics--2006 update: a report from the American
      Heart Association Statistics Committee and Stroke Statistics Subcommittee.

PMID- 16407574
TI  - The presence of neurological soft signs along the psychosis proneness continuum.
AB  - Neurological soft signs have been observed in patients with schizophrenia and
      their relatives. However, it has not been considered whether the increased rates
      of neurological soft signs are related to measures of psychosis proneness in the
      general population. We tested this hypothesis in a group of normal volunteers (n
      = 28) who scored highly for positive schizotypy when assessed online and a
      control group (n = 33) who scored below the mean. Compared with the controls,
      high psychosis-prone individuals showed significantly higher Total and Other Soft
      Signs subscale scores on the Neurological Evaluation Scale. It appears that soft
      signs are also associated with psychosis proneness when measured in the general
      population, which suggests that soft signs are distributed along a continuum of
      risk for schizophrenia.

PMID- 16407576
TI  - Successful aging.

PMID- 16407577
TI  - Definitions and predictors of successful aging: a comprehensive review of larger
      quantitative studies.
AB  - OBJECTIVE: There is no consensual definition of "successful aging." Our aim was
      to review the literature on proportions of subjects meeting criteria and
      individual components of definitions of successful aging as well as correlates of
      these definitions. METHODS: We conducted a literature search for published
      English-language peer-reviewed reports of data-based studies of adults over age
      60 that included an operationalized definition of successful aging. The authors
      categorized the components of these definitions and independent variables
      examined in relation to successful aging (e.g., gender, education, and social
      contacts). RESULTS: The authors identified 28 studies with 29 different
      definitions that met our criteria. Most investigations used large samples of
      community-dwelling older adults. The mean reported proportion of successful agers
      was 35.8% (standard deviation: 19.8) but varied widely (interquartile range:
      31%). Multiple components of these definitions were identified, although 26 of 29
      included disability/physical functioning. The most frequent significant
      correlates of the various definitions of successful aging were age (young-old),
      nonsmoking, and absence of disability, arthritis, and diabetes. Moderate support
      was found for greater physical activity, more social contacts, better self-rated
      health, absence of depression and cognitive impairment, and fewer medical
      conditions. Gender, income, education, and marital status generally did not
      relate to successful aging. CONCLUSION: Despite variability among definitions,
      approximately one-third of elderly individuals were classified as aging
      successfully. The majority of these definitions were based on the absence of
      disability with lesser inclusion of psychosocial variables. Predictors of
      successful aging varied yet point to several potentially modifiable targets for
      increasing the likelihood of successful aging.

PMID- 16407578
TI  - When blue turns gray: postwarranty performance.
AB  - OBJECTIVE: The objective of this study was to review the lifestyle and
      expectations of a group of 86- to 87-year-old Yale College graduates at the time
      of their 65th reunion and to compare the results with equivalent data from the
      general public. METHODS: A five-page questionnaire was sent to the 263 living
      survivors of the Yale College class of 1939 at the time of their 65th reunion.
      RESULTS: One hundred fifty-one replies were received, some only partially
      completed. Median survival was 79 years. Among the more interesting results was a
      wide discrepancy (optimism) between the perceived quality of life and that which
      one would anticipate from the many physical disabilities of the study group.
      CONCLUSION: This is by nature a self-selected group of male octogenarians, but
      their lifestyle and medical disabilities fit with the general population; their
      attitude toward being elderly is remarkably positive, and their personal and
      civic performance continues beyond expectations.

PMID- 16407579
TI  - Successful mental health aging: results from a longitudinal study of older
      Australian men.
AB  - OBJECTIVE: The authors investigated the associations of medical and lifestyle
      factors with the mental health of men in their 80s. METHODS: This was a
      prospective study of a community-representative cohort of older men. Successful
      mental health aging was defined as reaching age 80 years with Mini-Mental State
      Examination score (MMSE) of 24 or more and Geriatric Depression Scale-15 items
      (GDS-15) score of 5 or less. RESULTS: Of 601 men followed for 4.8 years, 76.0%
      enjoyed successful mental health aging. Successful mental health aging was
      inversely associated with age (hazard ratio [HR] = 0.87; 95% confidence interval
      [CI]: 0.81-0.94), non-English-speaking background (HR = 0.42; 95% CI: 0.21-0.85),
      and the consumption of full-cream milk (HR = 0.63; 95% CI: 0.45-0.89), and
      directly associated with high school or university education (HR = 1.92; 95% CI:
      1.34-2.75) and vigorous (HR = 1.89; 95% CI: 1.17-3.05) and nonvigorous physical
      activity (HR = 1.50; 95% CI: 1.05-2.14). Marital status, smoking and alcohol use,
      weekly consumption of meat or fish, and a medical history of
      hypercholesterolemia, hypertension, diabetes, myocardial infarction, and stroke
      were not associated with mental health outcomes in men aged 80 years or over.
      CONCLUSION: Three in four men who reach age 80 years undergo successful mental
      health aging. Factors associated with successful mental health aging include
      education and lifestyle behaviors such as physical activity. Lifestyle
      modification by means of increasing physical activity and reducing saturated fat
      intake may prove to be a safe, inexpensive, and readily available strategy to
      help maximize the successful mental health aging of the population.

PMID- 16407580
TI  - Cognitive functioning as a predictor of functional disability in later life.
AB  - OBJECTIVE: The contribution of cognitive functioning on multiple levels of
      functional disability and mortality over two years as well as individual
      activities of daily living (ADLs) and instrumental activities of daily living
      (IADLs) tasks, in a sample of older U.S. adults was examined. METHODS: A total of
      4,077 U.S. adults (1,493 males and 2,584 females) aged > or =70 years (mean =
      76.35 years) from the Second Longitudinal Study of Aging (1997/1998-1999/2000)
      were examined using an adapted Telephone Interview of Cognitive Status (TICS),
      ADLs, and IADLs. RESULTS: Multivariate logistic regression investigated cognition
      as a predictor of five mutually exclusive levels of functional disability. People
      with the lowest level of cognition had greater odds of mortality at follow-up
      (adjusted odds ratio [AOR] = 2.86, 95% confidence interval [CI] = 1.94-4.20), ADL
      and IADL disability (AOR = 1.58, 95% CI = 1.15-2.16), ADL disability (AOR = 1.83,
      95% CI = 1.27-2.64), or IADL disability (AOR = 1.22, 95% CI = 0.86-1.71) than
      those who were disability-free. Cognitive functioning was not predictive of
      individual ADL tasks but was predictive of the IADL tasks of preparing meals,
      shopping for groceries, managing money, telephone use, light housework, and
      medications but not heavy housework. CONCLUSION: Persons with lower levels of
      cognitive functioning were more likely to die or become disabled than those with
      higher levels of cognition. Changes in cognitive functioning might serve as an
      early indicator of neurologic and medical factors.

PMID- 16407581
TI  - Correlates of self-rated successful aging among community-dwelling older adults.
AB  - OBJECTIVE: There is no consensus on how to define successful aging. The authors
      sought to determine the correlates of self-rated successful aging as well as its
      correspondence with major researcher-defined criteria. METHODS: Participants were
      205 community-dwelling adults over age 60. A questionnaire survey asked the
      participants to rate their own degree of successful aging and inquired about
      demographic characteristics, medical history, activity levels, resilience, daily
      functioning, and health-related quality of life (Medical Outcomes study 36-item
      Short-Form [MOS-SF-36]). Participants' subjective ratings of successful aging
      were contrasted with sets of researcher-defined criteria, and correlates of
      subjectively rated successful aging were examined. RESULTS: Ninety-two percent of
      the participants rated themselves as aging successfully. A majority of them also
      met other research criteria for successful aging such as independent living,
      mastery/growth, and positive adaptation but not those requiring an absence of
      chronic medical illness or physical disability. Higher SF-36 scores as compared
      with a published sample indirectly corroborated participants' subjectively rated
      successful aging. Subjective ratings of successful aging were significantly
      correlated with higher scores on health-related quality of life as well as
      resilience, greater activity, and number of close friends but not with several
      demographic characteristics. CONCLUSION: Most community-dwelling older adults
      viewed themselves as aging successfully despite having chronic physical illnesses
      and some disability. Longitudinal studies of the reliability and validity of
      subjective ratings of successful aging are warranted.

PMID- 16407582
TI  - Adaptive task prioritization in aging: selective resource allocation to postural
      control is preserved in Alzheimer disease.
AB  - OBJECTIVE: With age, the performance of multiple tasks decreases, a pattern
      exaggerated in Alzheimer disease (AD). At the same time, recent research, based
      on adaptive theories of healthy aging, indicates a preference of older adults to
      allocate resources toward tasks of higher immediate value (e.g., postural
      control). This study investigated whether such models also hold for pathologic
      cognitive aging. METHOD: Using a dual-task paradigm, the authors combined a
      working memory with a postural control task under easy and difficult conditions
      in patients with AD, older adults, older adults low on performance on a cognitive
      marker test, and young adults (N = 40). Participants repeatedly performed a
      cognitive and a postural control task both simultaneously and in isolation over
      the course of eight sessions. RESULTS: Consistent with earlier studies on divided
      attention in age and AD, the authors found large dual-task performance decrements
      with age and more so in AD. When not challenged, patients with AD showed large
      performance decrements under dual-task conditions in both postural control and
      working memory. With increasing difficulty in the postural control task, however,
      older adults, and more so patients with AD, maintained a high level of
      functioning in postural control, as compared with working memory. CONCLUSION: The
      findings indicate that the theory of selective optimization with compensation
      extends to pathologic aging and have broad implications for models of dual-task
      performance and executive control in aging and AD.

PMID- 16407583
TI  - Retrospective analysis of diabetes risk in elderly patients with dementia in
      olanzapine clinical trials.
AB  - OBJECTIVE: The objective of this study was to evaluate the association of
      established risk factors for treatment-emergent diabetes (TED) among patients
      over 65 years of age with dementia who received treatment with olanzapine.
      METHODS: This was a post hoc analysis of data pooled from seven olanzapine
      clinical trials, which included patients over 65 years of age with dementia. The
      association of established risk factors for TED was evaluated using categorical
      and time-to-event analysis. TED was defined as two casual (fasting or nonfasting)
      glucose values > or =200 mg/dL at any time after baseline or one casual glucose
      value > or =200 mg/dL at the final visit, initiation of antidiabetic medication,
      or new clinical diagnosis of diabetes. RESULTS: Elderly patients subsequently
      identified with TED (N = 29, 2.1%) had similar baseline body mass indices (24
      kg/m(2)) and were similar in age (82 versus 80 years) to those who did not have
      TED. Cox proportional hazards model identified only elevated casual glucose (> or
      =140 mg/dL) measure at baseline to be significantly associated with the
      development of TED (hazard ratio [HR] = 11.2, p <0.0001) in this elderly cohort.
      Other clinical risk factors, like body mass index > or =25 (HR = 0.86), 7% weight
      gain (HR = 2.26), and antipsychotic treatment (HR = 1.36) were not significant.
      CONCLUSION: In elderly patients with dementia enrolled in olanzapine clinical
      trials, an elevated casual glucose (> or =140 mg/dL) at baseline was the only
      risk factor significantly associated with subsequent development of TED. Risk of
      diabetes in these studies was not significantly associated with antipsychotic
      treatment group assignment.

PMID- 16407585
TI  - Antidepressant class and dosing among older Mexican Americans: application of
      geropsychiatric treatment guidelines.
AB  - OBJECTIVE: The objective of this study was to characterize patterns and
      correlates of antidepressant drugs (AD) among older Mexican Americans (MAs).
      METHODS: This study consisted of a cross-sectional, community-based sample from
      Northern California. AD class and dosing label information were inventoried and
      compared with Expert Consensus Guidelines for geriatric depression
      pharmacotherapy. RESULTS: Overall, 7.1% had been prescribed an AD, but 4.9% were
      within starting dose ranges. Fewer ADs (3.9%) were consistent with Consensus
      class and dose guidelines. Depressive symptoms and diabetes were significant
      positive predictors of ADs. Recent immigrants had lower odds of AD prescriptions.
      CONCLUSIONS: AD prescriptions among older MAs are low. Omitting AD class and
      dosing information may overestimate pharmacotherapy for geriatric depression.

PMID- 16407584
TI  - The role of cardiovascular disease in the identification and management of
      depression by primary care physicians.
AB  - OBJECTIVE: The objective of this study was to describe the influence of
      cardiovascular disease (CVD) on identification and management of depression by
      primary care physicians. METHOD: Three hundred fifty-five adults with and without
      significant depressive symptoms who were screened in primary care offices and
      invited to participate completed a baseline in-home assessment. CVD was assessed
      by self-report and psychologic status was assessed with commonly used, validated
      standard questionnaires. At the index visit, doctors' ratings of depression and
      reports of active management were obtained on 340 of the 355 patients who
      completed in-home interviews. RESULTS: Older adults who reported heart failure
      were more likely to be identified as depressed than were older adults who did not
      report heart failure (unadjusted odds ratio [OR]: 2.34; 95% confidence interval
      [CI]: 1.13-4.85; Wald chi(2) = 5.20, df = 1, p = 0.023). In multivariate models
      that controlled for potentially influential characteristics such as age, marital
      status, education, ethnicity, functional status, level of depression, cognitive
      impairment, attitudes about depression, use of medical care, and number of
      medications, the findings remained statistically significant. Among older adults
      identified as depressed, older adults with heart failure were significantly less
      likely to be actively managed for depression than were older adults without heart
      failure (unadjusted OR: 0.33; 95% CI: 0.14-0.76; Wald chi(2) = 6.73, df = 1, p =
      0.009). After controlling for potentially influential covariates, these findings
      remained substantially unchanged. CONCLUSIONS: CVD, in particular heart failure,
      may influence the identification and management of depression among older
      patients by primary care physicians. The findings underlie the importance of
      developing interventions that integrate the management of depression and CVD in
      primary care settings.

PMID- 16407586
TI  - Psychosocial and vascular risk factors for depression in the elderly.
AB  - OBJECTIVE: The objective of this study was to examine two competing hypotheses as
      they relate to the relationship between vascular and psychosocial risk factors
      for late-life depression. The stress-vulnerability hypothesis predicts that the
      depressogenic effect of psychosocial risk is stronger in the presence of
      cardiovascular risk factors (CVRFs). The other predicts that psychosocial risk
      factors and vascular risk factors are independent pathways to depression and that
      there is no combined effect of vascular risk factors and life stress. METHOD:
      This study consisted of a longitudinal design (baseline, six-, and 12-month
      follow-up) predicting new episodes of significant depressive symptoms (CES-D >16)
      in 1,474 community-dwelling elders with low levels of depression at baseline (CES
      D <8). RESULTS: There was a significant interaction between stress at wave 2 and
      CVRFs at baseline such that stress was a stronger predictor of wave 2 depression
      in participants who had two or more CVRFs. There was no evidence that CVRFs
      played a larger role in depression not preceded by a stressful life event than in
      depression that was preceded by a stressful life event. CONCLUSIONS: The
      depressogenic effect of stress was stronger in the presence of significant
      vascular risk (CVRFs). Vascular risk may increase one's vulnerability to
      depression by exacerbating the impact of stress on depression. One hypothesis for
      this finding is that vascular disease disrupts mood regulation circuits in the
      brain, which decrease its ability to respond to stressful events.

PMID- 16407587
TI  - Gastrointestinal stem cells. III. Emergent themes of liver stem cell biology:
      niche, quiescence, self-renewal, and plasticity.
AB  - This essay will address areas of liver stem/progenitor cell studies in which
      consensus has emerged and in which controversy still prevails over consensus, but
      it will also highlight important themes that inevitably should be a focus of
      liver stem/progenitor cell investigations in coming years. Thus concepts
      regarding cell plasticity, the existence of a physiological/anatomic stem cell
      niche, and whether intrahepatic liver stem/progenitor cells comprise true stem
      cells or progenitor cells (or both) will be approached in some detail.

PMID- 16407588
TI  - Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake: possible
      role in steatosis.
AB  - Hepatic steatosis is a growing public health concern. Nonalcoholic fatty liver is
      increasingly common in Western societies and may lead to steatohepatitis,
      fibrosis, and cirrhosis, possibly triggered by lipid peroxidation. The relation
      of fatty liver to obesity, type II diabetes, and/or metabolic syndrome is
      significant. One aspect these related disorders share is increased serum-free
      fatty acids, which may be taken up by hepatocytes. Uptake of fatty acids in
      excess of metabolic requirements will lead to storage as triglycerides, resulting
      in steatosis and providing substrate for lipid peroxidation. Fatty acid uptake
      may be crucial to understanding steatosis.

PMID- 16407589
TI  - Iron imports. IV. Hepcidin and regulation of body iron metabolism.
AB  - Hepcidin, a small peptide synthesized in the liver, controls extracellular iron
      by regulating its intestinal absorption, placental transport, recycling by
      macrophages, and release from stores. Hepcidin inhibits the cellular efflux of
      iron by binding to and inducing the degradation of ferroportin, the sole iron
      exporter in iron-transporting cells. In turn, hepcidin synthesis is increased by
      iron loading and decreased by anemia and hypoxia. Hepcidin is markedly induced
      during inflammation, trapping iron in macrophages, decreasing plasma iron
      concentrations, and contributing to the anemia of inflammation. Hepcidin
      deficiency due to the dysregulation of its synthesis causes most known forms of
      hemochromatosis.

PMID- 16407590
TI  - Physiologically relevant increase in temperature causes an increase in intestinal
      epithelial tight junction permeability.
AB  - The effects of physiologically relevant increase in temperature (37-41 degrees C)
      on intestinal epithelial tight junction (TJ) barrier have not been previously
      studied. Additionally, the role of heat-shock proteins (HSPs) in the regulation
      of intestinal TJ barrier during heat stress remains unknown. Because heat-induced
      disturbance of intestinal TJ barrier could lead to endotoxemia and bacterial
      translocation during physiological thermal stress, the purpose of this study was
      to investigate the effects of modest, physiologically relevant increases in
      temperature (37-41 degrees C) on intestinal epithelial TJ barrier and to examine
      the protective role of HSPs on intestinal TJ barrier. Filter-grown Caco-2
      intestinal epithelial cells were used as an in vitro intestinal epithelial model
      system to assess the effects of heat exposure on intestinal TJ barrier. Exposure
      of filter-grown Caco-2 monolayers to modest increases in temperatures (37-41
      degrees C) resulted in a significant time- and temperature-dependent increases in
      Caco-2 TJ permeability. Exposure to modest heat (39 or 41 degrees C) resulted in
      rapid and sustained increases in HSP expression; and inhibition of HSP expression
      produced a marked increase in heat-induced increase in Caco-2 TJ permeability (P
      < 0.001). Heat exposure (41 degrees C) resulted in a compensatory increase in
      Caco-2 occludin protein expression and an increase in junctional localization.
      Inhibition of HSP expression prevented the compensatory upregulation of occludin
      protein expression and produced a marked disruption in junctional localization of
      occludin protein during heat stress. In conclusion, our findings demonstrate for
      the first time that a modest, physiologically relevant increase in temperature
      causes an increase in intestinal epithelial TJ permeability. Our data also show
      that HSPs play an important protective role in preventing the heat-induced
      disruption of intestinal TJ barrier and suggest that HSP mediated upregulation of
      occludin expression may be an important mechanism involved in the maintenance of
      intestinal epithelial TJ barrier function during heat stress.

PMID- 16407592
TI  - Nursing and medicine: continuing challenges.

PMID- 16407591
TI  - Roles of anandamide in the hepatic microcirculation in cirrhotic rats.
AB  - Cannabinoids have been reported to participate in the pathogenesis of peripheral
      vasodilatation in cirrhosis. However, their roles in increased intrahepatic
      resistance (IHR) in cirrhotic livers are unknown. We aimed to investigate the
      effects of cannabinoids in the hepatic microcirculation of cirrhotic rats
      produced by bile duct ligation. In isolated liver perfusion, portal perfusion
      pressure (PPP) and the production of eicosanoids in the perfusate were measured.
      In addition, various hepatic protein levels [cyclooxygenase (COX) isoform and 5
      lipoxygenase (5-LOX)] were also determined. Finally, concentration-response
      curves for PPP and the corresponding production of eicosanoids in response to
      anandamide (1.44 x 10(-10)-1.44 x 10(-3) M) after indomethacin (COX inhibitor),
      piriprost (5-LOX inhibitor), or furegrelate (thromboxane A(2) synthase inhibitor)
      preincubation were obtained. The study showed that cirrhotic livers had
      significantly higher levels of PPP, COX-2 and 5-LOX protein expression, and
      production of thromboxane B(2) (TXB(2)) and cysteinyl leukotrienes (Cys-LTs) than
      normal livers. Anandamide induced a dose-dependent increase in PPP in both normal
      and cirrhotic livers. The anandamide-induced increase in PPP was found
      concomitantly with a significant increase in TXB(2) and Cys-LT production in the
      perfusate. In response to anandamide administration, cirrhotic livers exhibited a
      significantly greater increase in IHR and production of TXB(2) and Cys-LTs than
      normal livers. Indomethacin and furegrelate, but not piriprost, significantly
      ameliorated the anandamide-induced increase in IHR in cirrhotic livers. In
      conclusion, anandamide plays, in part, an important role in increased IHR of
      cirrhotic livers. The anandamide-induced increase in IHR in cirrhotic livers may
      be mediated by increased COX-derived eicosanoid (mainly thromboxane A(2))
      production.

PMID- 16407593
TI  - Rogerian science-based nursing theories.
AB  - In this column, the author provides a general overview of selected theories
      derived from Rogerian nursing science. After a brief discussion of the Rogerian
      perspective, she highlights representative theories. She suggests that ongoing
      development of proposed theories has been relatively slow for two main reasons.
      First, scholars still use the 1970 book as a major reference. Unfortunately,
      despite her promise to do so, Rogers never updated the 1970 book and admitted on
      many occasions that it would more accurately reflect her refinement of her
      science if a major portion of the pages were torn out. Second, theories were
      often proposed by doctoral candidates who changed focus in their careers
      postdoctorate. Despite this, there is a fascinating body of theories in various
      stages of development for Rogerian scholars to pursue.

PMID- 16407594
TI  - The researcher-person-family process.
AB  - The author discusses the importance and some of the challenges of conducting
      qualitative family nursing research in a way that honors the meaning potential of
      the family. Examples of studies of low income families, families with children
      with special circumstances, and families with members with cancer are discussed.
      The use of the arts and humanities to explore the meaning potential of families
      is also discussed.

PMID- 16407595
TI  - The interplay between the abstract and the particular: research ethics standards
      and the practice of research as symbolic.
AB  - Ethical standards for research with human participants are increasingly
      important. With respect to nursing research these standards are symbolic of the
      interplay between the abstract theoretical aspects of bioethical standards and
      the particulars of nursing practice. In this column, this interplay is symbolized
      as a reflective equilibrium. These standards are argued to symbolize not only the
      dialectic relationship between the abstract and the particular in ethics, but
      also the general lack of a nursing specific articulation of ethical standards.
      Further understanding of the distinctiveness of nurses' moral judgments and
      knowledge is presented as necessary in strengthening the reflective equilibrium.

PMID- 16407596
TI  - Reflections on the prairie as a creative teaching-learning place.
AB  - In this column, the author reflects on characteristics of the prairie land of
      South Dakota and how it contributes to a creative teaching-learning place.
      Attributes of the prairie that are linked with creative teaching-learning include
      prairie as a space of aloneness and solitude, prairie as a boundless seeing what
      may be, prairie as contradiction and paradox, and prairie as possibility. These
      attributes of the prairie are explored through the author's personal experience,
      theoretical literature on creativity and teaching-learning, and literature from
      Parse's theory of human becoming.

PMID- 16407597
TI  - Using the Neuman systems model for best practices.
AB  - Human beings with unmet needs related to their health and illnesses are the
      central focus of the domain of nursing. It is proposed in this column that nurses
      who conduct their practice from a nursing theory base, while assisting
      individuals and families to meet their health needs, are more likely to provide
      comprehensive, individualized care that exemplifies best practices. The Neuman
      systems model has been widely acclaimed to guide practice, yet specific examples
      are few in the published literature. The purpose of this column is to present two
      case studies based upon Neuman systems model; one case is directed toward family
      care, and the other demonstrates care with an individual. Theory-based exemplars
      serve as teaching tools for students and practicing nurses. These case studies
      illustrate how nurses' actions, directed by Neuman's wholistic principles,
      integrate evidence-based practice and generate high quality care.

PMID- 16407598
TI  - The practice turn in nursing epistemology.

PMID- 16407599
TI  - Nursing theory and practice: connecting the dots.
AB  - The authors propose connecting the dots among theory, practice, and research by
      adopting an expanded conceptual-theoretical-empirical structure of nursing
      knowledge and matrix process to guide the placement of nursing knowledge in a
      contextual whole. An overview of the theoretical journey of nursing knowledge
      development is contrasted with the journey from practice resulting in a theory
      practice disconnect. Both approaches are united to present an integrated view of
      the dimensions of the knowledge development of nursing as a professional
      discipline.

PMID- 16407600
TI  - Feeling respected: a Parse method study.
AB  - This article reports a Parse research study on feeling respected with 10
      participants. The finding of this study is the structure: The lived experience of
      feeling respected is fortifying assuredness amid potential disregard emerging
      with the fulfilling delight of prized alliances. The structure is discussed in
      light of the human becoming school of thought and related literature.

PMID- 16407601
TI  - Death as a transformation of wholeness: an "aha" experience of health as
      expanding consciousness.
AB  - A nurse-patient clinical experience is presented from a unitary transformative
      perspective. The experience is interpreted through Newman's theory of health as
      expanding consciousness. A brief description of Newman's theory is given in order
      to provide the reader with Newman's key terms and fundamental philosophical
      principles. The nurse-patient healing partnership is explained using Newman's
      terminology and theory of health as expanding consciousness. The purpose of this
      article is to advance the critical importance of uncompromised and nonfragmented
      nursing care in partnership with the irreducible whole person.

PMID- 16407602
TI  - Florence Nightingale and healthcare reform.
AB  - The purpose of this article was to examine the work of Florence Nightingale in
      light of her collaboration with William Farr, the eminent medical statistician.
      Nightingale's epidemiological investigations supported by Farr illustrated that
      attention to environmental cleanliness was an important factor in preventing
      spread of disease. Nightingale channeled her investigations to support hospital
      reforms and the need for an educated nurse who could provide better management of
      the hospital environment. Statistical support and solicited criticism allowed
      Nightingale to argue more forcefully for her reforms.

PMID- 16407603
TI  - Innovation in healthcare: a systematic review of recent research.
AB  - Research on innovations in healthcare organizations published between 1994 and
      2004 are here reviewed and summarized. The majority of the 31 identified studies
      dealt with the adoption of innovations and new practices and were cross-sectional
      designs applying quantitative methods, or multiple case studies applying
      qualitative methods. Five pathways for future research are recommended: (a)
      Multilevel approaches studying innovation simultaneously on individual, group,
      and organizational levels; (b) a combination of quantitative and qualitative
      data; (c) use of longitudinal designs (innovation both as the dependent and
      independent variable); (d) application of experimental designs in interventions;
      and (e) exploration of innovation generation and structural innovations.

PMID- 16407604
TI  - Pornography: reactions and reality.
AB  - The Greek word porne (harlot) paired with graphe (picture or writing) has for
      centuries been used for depiction of sexual activity from cave paintings to
      contemporary internet depictions, movies, and videos. Playboy-type magazines are
      considered "tame" today. This brief discussion will update busy physicians of all
      specialties as to how their patients may be using or overusing available explicit
      materials and will also assess the impact on the patients' current work and home
      adjustment.

PMID- 16407605
TI  - Recognition and prevention of cardiovascular disease in women.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality for women and
      among women, the number of deaths secondary to CVD is nearly twice the number of
      all cancer-related deaths. Mortality trends from 1979 to 2001 have shown a
      consistent decrease in cardiovascular mortality among men; however,
      cardiovascular mortality trends have remained steady or increased among women.
      This disparity in outcomes, in part, is secondary to a lack of awareness among
      women and their health care providers regarding a woman's risk for CVD. A woman's
      risk for CVD should be assessed at routine evaluation. Primary prevention,
      including lifestyle and medical interventions, should be undertaken based on risk
      assessment. Initiation of menopausal hormone therapy is not recommended for the
      prevention of coronary heart disease or stroke in women.

PMID- 16407606
TI  - Clinical acute renal failure: diagnosis and management.
AB  - Acute renal failure (ARF) is frequently encountered in the hospitalized setting.
      In this article, we discuss the etiology, pathogenesis, preventative therapies,
      and renal replacement strategies in patients with acute tubular necrosis, the
      most common form of hospitalized ARF.

PMID- 16407607
TI  - Amenorrhea: common causes and evaluation.
AB  - Amenorrhea, either primary (before menarche) or secondary (after menarche), is a
      frequently encountered clinical condition in the primary care office. A patient
      oriented approach, utilizing focused diagnostic studies, provides an etiology in
      the majority of cases.

PMID- 16407608
TI  - Hospital ethics case consultations: practical guidelines.
AB  - Hospital ethics committees provide education, assist in policymaking, and deliver
      consultation services. In this article, we describe the structure, operation, and
      institutional framework within which an ethics committee fulfills its missions,
      with emphasis on the consultation process.

PMID- 16407609
TI  - Current diagnosis and treatment of lyme disease.
AB  - In more than 80% of cases, Lyme disease presents with an erythema migrans rash,
      but its characteristics can vary. Carditis, cranial palsies, lymphocytic
      meningitis, oligoarticular arthritis are manifestations of disseminated
      infection. Serological tests are helpful, but must be interpreted with caution.
      Standard antibiotic treatment regimens are highly effective.

PMID- 16407610
TI  - Physical activity and diabetes mellitus.
AB  - Diabetes mellitus (DM), a metabolic syndrome consisting of two main groups, type
      1 and 2, is characterized by absolute or relative insulin deficiency or insulin
      resistance. Individuals with DM take part in physical activity for health
      promotion, disease management, and or recreational or competitive sports. Several
      studies confirm the beneficial role of physical activity in favorably altering
      the prognosis of DM. Exercise as a therapeutic strategy has potential risks, too.
      Hence, sports medicine physicians caring for athletes with diabetes have several
      important responsibilities. Diabetic education; pre-participatory evaluation for
      vascular, neurological, retinal or joint disease; diabetic status and control;
      promotion of blood glucose self-monitoring; and individualized dietary,
      medication, and physical activity plans are essential to achieve safe and
      enjoyable outcomes in individuals with diabetes who are embarking on physical
      activity.

PMID- 16407611
TI  - Evolving molecular-based targeted therapy for cancer: an exciting field.
AB  - The development of molecular biology tools has led to the identification of
      numerous therapeutic targets in cancer cells. In this article, we discuss the
      rational and clinical data supporting the use of agents that selectively target
      epidermal and vascular endothelial growth factors in selected cancers.

PMID- 16407612
TI  - Radiofrequency ablation for locally advanced cancer of the pancreas.

PMID- 16407613
TI  - Systematic review of peri-operative nutritional supplementation in patients
      undergoing pancreaticoduodenectomy.
AB  - BACKGROUND: Although nutritional supplementation is established in surgical
      practice, studies on feeding patients undergoing pancreaticoduodenectomy utilise
      widely disparate protocols, include small numbers of patients and have disparate
      endpoints. The aim of this study is to carry out a systematic review of peri
      operative nutritional supplementation in patients undergoing
      pancreaticoduodenectomy in order to identify consistent themes. METHODS: Searches
      of the MEDLINE and EMBASE databases yielded 10 studies examining nutritional
      support in 571 patients undergoing pancreaticoduodenectomy. Data were retrieved
      on: proportion of pre-operative weight loss, biochemical parameters (pre
      operative albumin and the presence of jaundice), type and duration of nutritional
      support and clinical outcome (morbidity, mortality and hospital stay). RESULTS:
      Pre-operative percentage weight loss was similar in all studies evaluated.
      Routine post-operative total parenteral nutrition (TPN) was associated with a
      higher incidence of complications. Enteral nutrition reduced infective
      complications. Cyclical nutrition was associated with a lower incidence of post
      operative gastric stasis. CONCLUSION: Clear themes emerge from this systematic
      review. Patients undergoing pancreaticoduodenectomy are nutritionally depleted at
      the time of surgery and the pre-operative period may present a window for
      intervention. Routine TPN is not beneficial. Routine post-operative enteral
      nutritional support, delivered on a cyclical basis appears to be the optimal mode
      of delivery.

PMID- 16407614
TI  - Tumour necrosis factor microsatellite haplotypes are associated with chronic
      pancreatitis.
AB  - CONTEXT: Alcohol is the major aetiological agent for both chronic pancreatitis
      and alcoholic liver disease. However, as only a minority of alcoholics develop
      either chronic pancreatitis or alcoholic liver disease, there are clearly genetic
      or environmental cofactors that determine individual susceptibility to these
      diseases. OBJECTIVE: To determine whether polymorphisms of the TNF gene may
      account for individual susceptibility to develop chronic pancreatitis or
      alcoholic liver disease. DESIGN: A controlled study. PATIENTS: We analyzed 73
      patients with chronic pancreatitis, 103 healthy controls, 39 patients with
      alcoholic liver disease and 29 alcoholics without liver or pancreatic disease.
      RESULTS: The intermediate/low TNF secreting haplotype a6b5c1d3e3 was over
      represented in chronic pancreatitis compared to healthy controls (OR=2.08; 95%
      CI: 1.07-4.06); P=0.019) and in alcoholic chronic pancreatitis compared to
      healthy controls (OR=2.08; 95% CI: 1.01-4.29; P=0.029). The high TNF secreting
      haplotypes, a2b3c1d1e3 and a2b5c2d4e3 were under-represented in chronic
      pancreatitis compared to healthy controls (OR=0.48; 95% CI: 0.22-1.04; P= 0.043)
      and in alcoholic chronic pancreatitis compared to alcoholic controls (OR=0.20;
      95% CI: 0.05-0.77; P=0.014), respectively. CONCLUSION: A reduced capacity to
      produce TNF may be responsible for the induction of chronic pancreatitis.

PMID- 16407615
TI  - Comparison of the effect of non-ionic and ionic contrast agents on pancreatic
      histology in a canine model.
AB  - CONTEXT: Pancreatitis is the most frequent complication of endoscopic retrograde
      cholangiopancreatography. Controversy exists whether low osmolarity non-ionic
      contrast agents lessen the rate of pancreatitis and pancreatic injury. To
      evaluate we used a canine model to compare pancreatography performed with ionic
      and non-ionic contrast. DESIGN: Dogs were anesthetized and underwent open
      transduodenal cannulation of the main pancreatic duct under fluoroscopic control
      until complete acinarization was achieved to maximize injury. Three dogs received
      diatrozate, an ionic contrast agent with osmolarity of 1,415 mosM and three dogs
      were injected with omnipaque a non-ionic agent with osmolarity of 672 mosM. MAIN
      OUTCOME MEASURES: Serial amylase and white cell counts were followed for 48 hours
      at which time dogs were sacrificed. Each pancreas was then examined for evidence
      of pancreatitis and cellular injury with both light and electron microscopy.
      RESULTS: All animals developed significant hyperamylasemia and elevated white
      blood cell counts, without significant difference in the mean peak amylase
      (10,721 U/L vs. 9,367 U/L, P=0.876) or white cell counts (25.8 k/mL vs. 24.1
      k/mL, P=0.586) between the ionic and non-ionic contrast groups. Light microscopy
      showed no evidence of pancreatitis in either group of dogs. Electron microscopy
      showed cellular injury of the ductal cells in two dogs injected with non-ionic
      contrast. CONCLUSION: In a pancreatic canine model, low osmolarity, non-ionic
      contrast does not appear to lessen cellular injury.

PMID- 16407616
TI  - Combined chemoradiotherapy for isolated local recurrence after primary resection
      of pancreatic cancer.
AB  - CONTEXT: Primary resectability is expected in up to 20% of pancreatic cancer
      patients. While most patients relapse with distant metastases, approximately 30%
      of patients show isolated local recurrence without evidence of distant
      metastases. OBJECTIVE: The present analysis investigates the efficacy of
      chemoradiotherapy in this particular patient group. DESIGN: Retrospective study.
      PATIENTS: Eighteen consecutive pancreatic cancer patients presenting with
      isolated locoregional recurrence after surgical resection. The median interval
      between primary surgery and diagnosis of local recurrence was 10.4 months (range:
      2.0-19.3 months). INTERVENTIONS: Patients received 3-D conformal radiation with
      45 Gy in 25 fractions of 1.8 Gy/day. Simultaneous chemotherapy was employed
      either with continuous 5-FU infusion, partly in combination with gemcitabine, or
      with gemcitabine and cisplatin. Sequential chemotherapy with gemcitabine and
      cisplatin was given to some patients before and after the chemoradiotherapy.
      RESULTS: In 17 of the 18 patients included, radiotherapy was employed at the
      intended dose. While WHO grade 3-4 gastrointestinal toxicity was not reported,
      hematotoxicity was more pronounced. Grades 3 and 4 leukocytopenia occurred in 4
      patients (22.2%) and 1 (5.6%) patient, respectively, and grades 3 and 4
      thrombocytopenia occurred in 4 patients (22.2%) and 1 patient(5.6%),
      respectively. Six (37.5%) complete remissions, 6 (37.5%) partial remissions, and
      4 (25.0%) stable diseases were noted in 16 evaluable patients. Median progression
      free survival calculated from the start of the chemoradiotherapy was 14.7 months
      (range: 8.4-21.0 months) . Seven (28.9%) patients had another local relapse,
      while 11 (61.1%) patients developed distant metastases. Median overall survival
      from the start of the chemoradiotherapy was 17.5 months (95% CI: 15.6-19.4
      months) and median survival from the initial diagnosis was 27.2 months (95% CI:
      23.9-30.6 months). CONCLUSION: The data provide a first indication that
      chemoradiotherapy is feasible and may be an effective treatment option in those
      patients who present with local metastasis after primary surgery for pancreatic
      cancer.

PMID- 16407617
TI  - Report of three cases of chronic pancreatic fistulas treated with prolamine as a
      sclerosing substance following pancreatic resection.
AB  - CONTEXT: Pancreatic fistulas are one of the most common and important
      complications after pancreatic resection and their consequences are a life
      threatening event. Thus, they must be treated in the best way and resolved as
      soon as possible to avoid their morbidity. METHODS: Three cases of pancreatic
      fistula following pancreatic resection were reported. They were treated with
      percutaneous embolization using a sclerosing substance, prolamine, injected into
      the Wirsung duct via drainage catheter. RESULTS: No complications of the
      technique were revealed and closure of the pancreatic fistula was obtained
      shortly thereafter. CONCLUSIONS: The technique is safe and simple and can be
      repeated several times. It allows good results without complications. Finally, it
      avoids additional surgery allowing a shorter recovery time and a lower risk of
      morbidity.

PMID- 16407618
TI  - Squamous cell carcinoma of the pancreas: report of a case and review of the
      literature.
AB  - CONTEXT: Although, squamous metaplasia of the ductal columnar cells can be
      observed during periods of inflammation, squamous cell pancreatic carcinoma is an
      extremely rare tumour. CASE REPORT: We present the case of a 72-year-old man who
      presented to our hospital with painless obstructive jaundice. After careful and
      adequate staging investigations that revealed a malignant mass in the head of
      pancreas he underwent a laparotomy which revealed an inoperable pancreatic
      cancer. Palliative bypass procedure was done. The biopsy specimens revealed a
      squamous cell cancer. CONCLUSION: Pure squamous cell carcinoma of the pancreas is
      a very rare malignancy. In most cases it is not possible to make a pre-operative
      histological diagnosis and curative resection is unlikely because of
      dissemination at the time of initial diagnosis or laparotomy.

PMID- 16407619
TI  - Sequential CT evaluation of isolated non-penetrating pancreatic trauma.
AB  - CONTEXT: Isolated pancreatic injuries resulting from non-penetrating trauma are
      rare. CT is currently the modality of choice in evaluating pancreatic injury.
      Delay in recognizing patients who need immediate surgery is an important cause of
      increased morbidity due to specific pancreatic complications. CASE REPORT: A 47
      year-old man with blunt abdominal trauma after a car accident underwent a CT
      scan. Initial CT findings included diffuse pancreatic enlargement suggestive of
      isolated grade 1 pancreatic injury. A follow-up CT scan 3 days later revealed a
      fracture line at the pancreatic body. Subsequent surgical exploration confirmed
      the suspicion of concomitant duct transection. Seven months after surgery, a
      pseudocyst had formed adjacent to the site of the injury. CONCLUSIONS: This case
      demonstrates the potential importance of serial CT scans in the diagnosis,
      grading and management of isolated pancreatic injury.

PMID- 16407620
TI  - Acute pancreatitis associated with neuroendocrine tumor of the pancreas.
AB  - CONTEXT: Endocrine tumors are a less commonly known cause of acute pancreatitis.
      This report presents the case of a patient who have had acute pancreatitis
      secondary to a pancreatic endocrine neoplasm. The majority of the cases
      previously reported were non-functioning tumors and the pancreatitis tended to be
      mild. Moreover, the majority of the tumors were diagnosed in advanced stages,
      hindering curative treatment. CASE REPORT: A 31-year-old female patient presented
      with epigastric pain and a history of recurrent acute pancreatitis. Preoperative
      imaging investigation showed a dilation of the distal portion of the main
      pancreatic duct and intra-operative ultrasound demonstrated a mild stricture of
      the main pancreatic duct at the body of the pancreas. Frozen-section examination
      revealed a malignant neoplasm, subsequently identified as a neuroendocrine
      carcinoma, and a distal pancreatectomy with splenectomy was performed. Acute
      pancreatitis was an early symptom in this patient who underwent a hopefully
      curative resection. CONCLUSION: The authors conclude that, in patients with acute
      pancreatitis of unknown origin, the possibility of a non-functioning
      neuroendocrine tumor should be investigated.

PMID- 16407621
TI  - Acute pancreatitis associated with brucellosis.
AB  - CONTEXT: Acute pancreatitis can be caused by a variety of infectious agents but
      it is regarded as an extremely rare complication of brucellosis. CASE REPORT: We
      briefly describe a 56-year-old man who presented with acute pancreatitis, fever,
      myalgia, and other clinical symptoms. Brucella melitensis was cultured from his
      blood. All clinical manifestations gradually resolved with the institution of
      intramuscular streptomycin and oral doxycycline therapy. CONCLUSION: Acute
      pancreatitis may rarely be a complication of infection with B. melitensis. In
      areas where brucellosis is endemic, it should be kept in mind that acute
      pancreatitis may result from infection with brucella organisms.

PMID- 16407622
TI  - Pancreatic metastasis of an ovarian malignant mixed Mullerian tumor identified by
      EUS-guided fine needle aspiration and Trucut needle biopsy.
AB  - CONTEXT: Malignant mixed Mullerian tumors are rare ovarian neoplasms that account
      for less than 2% of ovarian malignancies. They have a generally poor prognosis
      and often develop recurrent disease. To our knowledge, this is the first report
      of a malignant mixed Mullerian tumor with metastasis to the pancreas. The
      metastatic tumor was identified by endoscopic ultrasound guided fine needle
      aspiration (EUS-FNA) and Trucut needle biopsy of the pancreas. CASE REPORT: We
      describe a 69-year-old female with concomitant Duke's C adenocarcinoma of the
      colon and stage III-C malignant mixed Mullerian tumor that presented with
      malignant ascites, increasing abdominal girth and a pancreatic head mass. EUS
      revealed an 11 cm cystic mass in the head of the pancreas that was characterized
      as a carcinosarcoma/malignant mesodermal mixed tumor by EUS-FNA and Trucut needle
      biopsy. The tumor was morphologically identical to the surgical specimen of her
      ovarian mass. The patient was treated with palliative chemotherapy and a three
      month follow up CT scan did not reveal any new metastatic lesions. CONCLUSION:
      The pancreas is a rare site of metastasis and more commonly seen in renal cell
      carcinoma, melanoma or lung tumors; amongst others. Although ovarian
      adenocarcinoma has been reported as a primary site of pancreatic metastasis, it
      has not been previously described originating from a mixed Mullerian tumor of the
      ovary presenting as a cystic pancreatic head mass.

PMID- 16407623
TI  - Asymptomatic calcitonin-secreting tumor of the pancreas. A case report.
AB  - CONTEXT: Pancreatic endocrine tumors are unusual tumors arising from cells
      belonging generically to the amine precursor uptake and decarboxylation system.
      CASE REPORT: We present a case of a calcitonin-secreting pancreatic endocrine
      tumor in a 59-year-old male who presented at our Center with elevated calcitonin
      values. The patient was asymptomatic. Further investigation revealed a tumor, 80
      mm in diameter, in the pancreatic body and tail along with three metastatic
      lesions in segments III, V, and VIII of the liver. Following a distal
      pancreatectomy, splenectomy and wedge resection of segments III and V along with
      radiofrequency ablation of the segment VIII lesion, his serum calcitonin reached
      normal values. CONCLUSIONS: Calcitonin-secreting pancreatic endocrine tumors are
      often malignant and have a poor prognosis. We believe that an aggressive surgical
      approach may improve survival.

PMID- 16407624
TI  - Radiofrequency ablation of unresectable pancreatic carcinoma: feasibility,
      efficacy and safety.
AB  - CONTEXT: Unresectable pancreatic cancer has a dismal prognosis. Palliative
      surgery and chemo-radiotherapy have not produced significant improvement in
      survival. We evaluated the safety and the efficacy of radiofrequency ablation for
      cytoreduction of unresectable tumors of the pancreas. CASE REPORT: Radiofrequency
      ablation was performed in three patients with histologically proven unresectable
      cancer of the pancreas: two females and one male; 48, 60, and 66 years of age
      (mean 58 years). The sizes of the pancreatic tumors were 5.0, 6.5, and 8.0 cm
      (mean 6.5 cm), respectively. Two patients underwent radiofrequency ablation
      during an open operation while one patient had percutaneous CT guided
      radiofrequency ablation. All had endobiliary stenting for obstructive jaundice.
      Partial necrosis (up to 3 cm) of the tumor was achieved in all cases. There was
      no major morbidity or mortality. Self-limiting minor complications occurred in
      two patients. CONCLUSION: Radiofrequency ablation is a local ablative method used
      with increasing frequency and may be used safely for cytoreduction in locally
      advanced inoperable pancreatic malignancies. Further studies are required to
      ascertain whether this can improve survival/quality of life alone or in
      combination with other therapies.

PMID- 16407625
TI  - New approaches for the treatment of acute pancreatitis.
AB  - In recent years, a number of articles have been published on the treatment of
      acute pancreatitis in experimental models and most of them were published about
      animals with mild disease. However, it is difficult to translate these results
      into clinical practice. For example, infliximab, a monoclonal TNF antibody, was
      experimentally tested in rats and it was able to significantly reduce the
      pathologic score and serum amylase activity, and also alleviate alveolar edema
      and acute respiratory distress syndrome; no studies are available in clinical
      human acute pancreatitis. Another substance, such as interleukin 10, was
      efficacious in decreasing the severity and mortality of lethal pancreatitis in
      rats, but seems to have no effect on human severe acute pancreatitis. Thus, the
      main problem in acute pancreatitis, especially in the severe form of the disease,
      is the difficulty of planning clinical studies capable of giving hard
      statistically significant answers regarding the benefits of the various proposed
      therapeutic agents previously tested in experimental settings. According to the
      pathophysiology of acute pancreatitis, we may re-evaluate the efficacy of the
      drugs already available, such as gabexate mesilate, lexipafant and somatostatin
      which should be probably administered in a different manner. Of course, also in
      this case, we need large studies to test this hypothesis. Another great problem
      is prevention of the infection of pancreatic necrosis. A randomized study has
      been published to test the hypothesis that probiotics and specific fibres used as
      supplements in early enteral nutrition may be effective in reducing pancreatic
      sepsis and the number of surgical interventions. A study named PROPATRIA
      (Probiotic Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) has
      been planned to give a more robust confirmation to the previous study.
      Furthermore, the open question of the prevention of the fungal infection of
      necrosis is still being debated. Finally, the prevention of pain relapse after
      oral feeding in patients with mild or severe acute pancreatitis should be
      explored. Even if some studies exist on this issue, the question of optimal
      treatment is still unanswered. As in other diseases, obtaining results when
      treating patients with acute pancreatitis is difficult and will take continuous
      small steps.

PMID- 16407626
TI  - Probiotics and severe acute pancreatitis.

PMID- 16407628
TI  - What is the role of pancreas units today?
AB  - The study of pancreatic diseases requires specific knowledge and experience.
      There are many reasons for the need of a specific approach: pancreatic diseases
      are rare, their clinical presentation is often misleading, diagnostic
      investigations pose many challenges and pancreatic surgery is very complex. Due
      to these characteristics, it is difficult for a physician who only occasionally
      deals with a pancreatic disease to correctly manage it. For example, it is not
      sufficient to make a diagnosis of "pancreatic tumor", because we have to
      precisely define its extension and its relationship with the surrounding vessels,
      to recognize rare histological types different from adenocarcinoma, to have a
      "pancreatic" surgical experience to lessen the risk of serious surgical
      complications. On the other hand, several reports have shown that pancreatic
      resections have lower mortality rates and better long-term outcomes if carried
      out in Centers with a high caseload of patients. These considerations support the
      creation of Pancreas Units, not mere high-volume Departments specialized in
      pancreatic diseases, but multidisciplinary teams (composed of surgeons,
      oncologists, gastroenterologists, pathologists, radiologists, radiotherapists and
      different types of researchers) devoted to all aspects (etiology, pathogenesis,
      diagnosis, treatment) of pancreatic diseases. We think that the adoption of a
      Pancreas Unit model could represent the right answer to the recent changes
      observed in Medicine and could offer a better approach to patients with
      pancreatic diseases.

PMID- 16407629
TI  - Imaging techniques for acute necrotizing pancreatitis: multidetector computed
      tomography.

PMID- 16407630
TI  - Role of MR Imaging in the Diagnostic Work-up of Acute Pancreatitis.

PMID- 16407631
TI  - The quality of life in chronic pancreatitis: the clinical point of view.

PMID- 16407632
TI  - The quality of life in chronic pancreatitis: the endoscopist's point of view.

PMID- 16407633
TI  - The quality of life in chronic pancreatitis: the role of surgery.

PMID- 16407634
TI  - Radiotherapy and chemotherapy in pancreatic cancer. Topical issues and future
      perspectives.

PMID- 16407635
TI  - Solid-papillary tumors of the pancreas: histopathology.
AB  - A solid-pseudopapillary tumor is an uncommon and "enigmatic" pancreatic neoplasm,
      and the term encompasses the two most conspicuous histological features: solid
      and pseudopapillary areas. Grossly, it appears as a large solid, cystic or solid
      cystic mass frequently having necrotic and hemorrhagic zones. Histologically,
      solid-pseudopapillary tumors are generally characterized by solid areas
      alternating with a pseudopapillary pattern, and cystic spaces which are the
      results of degenerative changes occurring in the solid neoplasm. Its
      immunohistochemical pattern is very distinctive and neoplastic cells are
      consistently vimentin-, CD10- and CD56-positive. Some cases express focal
      positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin, neuron-specific
      enolase and synaptophysin. Progesterone receptors are frequently present.
      Keratins are not expressed or are found only focally. Endocrine and pancreatic
      enzyme markers are absent; the origin of solid-pseudopapillary tumors has not yet
      been clarified. Many investigators favor the theory that solid-pseudopapillary
      tumors originate from multipotent primordial cells while others suggest an extra
      pancreatic origin from genital ridge angle-related cells. Some controversy exists
      for both hypotheses. Solid-pseudopapillary tumors appear as a low malignancy
      tumor and only a small number of cases recur or develop metastases after
      resection. No pathological factors were found to correlate with the prognosis.
      Some histological features have recently been suggested to be associated with
      aggressive behavior.

PMID- 16407636
TI  - Pancreatic solid-cystic papillary tumor: clinical features, imaging findings and
      operative management.
AB  - Solid-cystic papillary tumors of the pancreas are very rare and, until today, 718
      cases have been reported in a review of the literature. Four patients affected by
      solid-cystic papillary tumors, observed in our Institute between January 1985 and
      July 2005, are reported. The clinicopathological, operative and survival data of
      this tumor were reviewed comparing our experience with a review of the
      literature. Solid-cystic papillary tumor have a preference for young women (age
      between 19-50 yrs) and show a large round, well-defined pancreatic mass(greater
      than 5 cm), clinically silent or with unspecific symptoms. The tumor is more
      frequently localized in the pancreas (80%) and is rarely a metastatic disease
      (20%). Surgical treatment with radical pancreatic resection of the tumor was
      performed in approximately 95% of the cases. In 467 patients, two-year survival
      was 97% (16 deaths) and 5-year survival was 95% (21 deaths). In conclusion,
      preoperative diagnosis of solid-cystic tumors of the pancreas is difficult but
      knowledge of its characteristic findings can aid in reaching a proper diagnosis.
      Surgery is the treatment of choice; it should be conservative in localized
      tumors, and aggressive, in non-localized tumors. The prognosis is very good, with
      long-term survival also in patients with metastases or unresectable tumors.

PMID- 16407637
TI  - Medical treatment of endocrine gastroenteropancreatic tumors.

PMID- 16407638
TI  - Surgical strategy in the treatment of pancreatic neuroendocrine tumors.
AB  - Endocrine pancreatic tumors are rare and their surgical treatment is often
      debated. This review analyzes the management and the different indications in
      functioning and non-functioning neoplasms. The choice among different procedures
      is described as well as the role of intra operative ultrasound. Moreover, the
      different patterns of tumor spread are considered (local, loco-regional and
      metastatic) along with the indications according to the main controversies
      relating to cytoreductive surgery, transplantation and multiple endocrine
      neoplasia type 1 patients.

PMID- 16407640
TI  - Intake of vitamin and mineral supplements in an elderly german population.
AB  - AIM: To assess the prevalence of vitamin and mineral supplement use in a free
      living elderly population and the contribution of these supplements to usual
      dietary intake. METHODS: Analyses are based on data obtained from 388 subjects
      (>or=60 years) participating in the longitudinal study on nutrition and health
      status in an ageing population in Giessen (GISELA), Germany, in 2002. Nutrient
      intake from food was assessed by means of a 3-day estimated dietary record.
      Supplement use was recorded over a period of 3 days using a self-administered
      questionnaire. RESULTS: Nearly half of the study population consumed at least 1
      supplement within these 3 days. The use of supplements was more prevalent among
      women than among men (51.5 vs. 33.9%). On average women consumed 2.03+/-1.30
      products and men 1.65+/-1.07 products. Magnesium, vitamin C and vitamin E were
      supplemented most often by men, while women supplemented magnesium, vitamin E and
      calcium most often. Most of the supplemented nutrients did not distinctly
      increase the average intake of the respective nutrients from the diet in this
      population. However, supplement use markedly decreased the proportions of elderly
      subjects with an intake below the current reference values for certain nutrients,
      particularly for vitamin E. CONCLUSION: Results indicate that the intake of
      supplements is a common behavior in the population under investigation and
      therefore has to be considered when nutrient intake is evaluated.

PMID- 16407639
TI  - Double-blind, randomised, controlled trial assessing controller medications in
      asthma.
AB  - BACKGROUND: The motive behind conducting this study was to determine if better
      control of asthma can be achieved by adding a second controller medication and to
      assess its use to reduce the dose of inhaled steroids. OBJECTIVES: The study
      aimed to determine whether either oral sustained-release theophylline or
      montelukast added to inhaled steroids improved clinical symptoms and pulmonary
      function test parameters when compared to high-dose steroids alone. METHODS:
      Ninety patients with incompletely controlled asthma were allocated, in a
      randomised, double-blind fashion, to one of three treatment groups: group A:
      double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral
      sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C:
      10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were
      forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow
      rate (PEFR). RESULTS: All three groups had improved FEV(1) and PEFR at 8 weeks (p
      < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval,
      CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than
      group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml)
      greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater
      improvement than group B (both p = 0.01). CONCLUSIONS: Addition of montelukast to
      budesonide is safe and results in greater improvement in pulmonary function test
      parameters than high-dose budesonide treatment or addition of theophylline.

PMID- 16407641
TI  - Bioavailability of apigenin from apiin-rich parsley in humans.
AB  - AIM: Absorption and excretion of apigenin after the ingestion of apiin-rich food,
      i.e. parsley, was tested. METHODS: Eleven healthy subjects (5 women, 6 men) in
      the age range of 23-41 years and with an average body mass index of 23.9 +/- 4.1
      kg/m2 took part in this study. After an apigenin- and luteolin-free diet, a
      single oral bolus of 2 g blanched parsley (corresponding to 65.8 +/- 15.5
      micromol apigenin) per kilogram body weight was consumed. Blood samples were
      taken at 0, 4, 6, 7, 8, 9, 10, 11 and 28 h after parsley consumption and 24-hour
      urine samples were collected. Apigenin was analyzed in plasma, urine and red
      blood cells by means of HPLC-ECD. RESULTS: On average, a maximum apigenin plasma
      concentration of 127 +/- 81 nmol/l was reached after 7.2 +/- 1.3 h with a high
      range of variation between subjects. For all participants, plasma apigenin
      concentration rose after bolus ingestion and fell within 28 h under the detection
      limit (2.3 nmol/l). The average apigenin content in 24-hour urine was 144 +/- 110
      nmol/24 h corresponding to 0.22 +/- 0.16% of the ingested dose. The flavone could
      be detected in red blood cells without showing dose-response characteristics.
      CONCLUSIONS: A small portion of apigenin provided by food reaches the human
      circulation and, therefore, may reveal biological effects.

PMID- 16407642
TI  - Influence of vitamin C and E supplementation on oxidative stress induced by
      hyperbaric oxygen in healthy men.
AB  - AIM: To investigate the effect of a 4-week vitamin C and E supplementation on
      oxidative stress induced by hyperbaric oxygen (HBO). METHODS: 19 healthy men were
      exposed to 3 sequential protocols, i.e. HBO (100% O2, 2.4 bar, 131 min) before
      (T1) and after 4 weeks of daily supplementation with 500 mg slow-release vitamin
      C and 272 IU vitamin E (T2). A normoatmospheric protocol (21% O2, 1.0 bar, 131
      min) served as control treatment (nonexposed). Blood samples were taken before
      (B) and immediately after (A) treatment. Plasma levels of vitamin A, C, E, beta
      carotene, reduced glutathione and malondialdehyde were measured by HPLC.
      Antioxidative capacity and lipid peroxides in plasma were analyzed by ELISA.
      RESULTS: HBO decreased vitamin C and antioxidative capacity (T1). At T1, Delta A 
      B of vitamin C and lipid peroxides was different from nonexposed. Vitamin
      supplementation increased plasma levels of vitamin C and E by 28 and 37%,
      respectively. Vitamin supplementation led to decreased concentrations of lipid
      peroxides and reduced glutathione. After supplementation, HBO decreased vitamin C
      and reduced glutathione. At T2, Delta A - B of vitamin C and lipid peroxides was
      significantly different from nonexposed. CONCLUSION: In humans, oxidative stress
      decreased plasma levels of vitamin C and antioxidative capacity and increased
      plasma lipid peroxides. Supplementation with vitamin C and E did not prevent
      these effects.

PMID- 16407643
TI  - Lower consumption of cow milk protein A1 beta-casein at 2 years of age, rather
      than consumption among 11- to 14-year-old adolescents, may explain the lower
      incidence of type 1 diabetes in Iceland than in Scandinavia.
AB  - AIM: To compare the consumption of the cow milk proteins A1 and B beta-casein
      among children and adolescents in Iceland and Scandinavia (Norway, Denmark,
      Sweden and Finland) as this might explain the lower incidence of type 1 diabetes
      (per 100,000/year, 0-14 years) in Iceland. METHODS: The consumption of A1 beta
      casein in each country among 2- and 11- to 14-year-old children was calculated
      from results on food intake and on cow milk protein concentration. The
      consumption values were then compared and evaluated against the incidence of type
      1 diabetes. RESULTS: There was a significant difference between the consumption
      of A1 (p = 0.034) as well as the sum of A1 and B (p = 0.021) beta-casein in
      Iceland and Scandinavia for 2-year-old children. In the same age group,
      consumption of A1 beta-casein correlated with the incidence of type 1 diabetes in
      the countries (r = 0.9; p = 0.037). No significant difference in consumption of
      A1 or the sum of A1 and B beta-casein was found for 11- to 14-year-old
      adolescents. CONCLUSION: This study supports that lower consumption of A1 beta
      casein might be related to the lower incidence of type 1 diabetes in Iceland than
      in Scandinavia. Additionally it indicates that consumption in young childhood
      might be of more importance for the development of the disease incidence than
      consumption in adolescence.

PMID- 16407644
TI  - Thermogenesis associated to the intake of a diet non-supplemented or supplemented
      with n-3 polyunsaturated fatty acid-rich fat, determined in rats receiving the
      same quantity of metabolizable energy.
AB  - The beneficial effects of n-3 polyunsaturated fatty acids (PUFA) are well known,
      but their consumption in western countries is chronically insufficient, and so it
      is recommended that diets should be supplemented with a fat rich in these fatty
      acids. However, the effect of such diets on the energy expenditure remains a
      controversial question. Precise data concerning the effect of using under the
      same metabolizable energy intake, a diet non-supplemented or supplemented with a
      fat rich in n-3 PUFA are not available. This type of information was obtained
      using rats at weaning fed a diet supplemented or non-supplemented with 10% of
      fish oil. Between the 30th and 60th day after starting the experiment, the energy
      and protein balance was established by means of the comparative slaughter method.
      The blood levels of different metabolites were also determined. Although total
      thermogenesis did not vary between the two groups, consumption of the fish oil
      diet led to a lower level of thermogenesis associated with the oxidation of
      protein, and a higher one of that associated with the oxidation of fat. We
      conclude that the thermic effect of feeding is a combination of independent
      processes. Due to their specific metabolism, n-3 PUFA may be considered essential
      compounds to maintain the energy balance.

PMID- 16407645
TI  - Prediction equation of resting energy expenditure in an adult Spanish population
      of obese adult population.
AB  - OBJECTIVE: The aim of our study was to evaluate the accuracy of the equations to
      estimate REE in obese patents and develop a new equation in our obese population.
      SUBJECTS AND METHODS: A population of 200 obesity outpatients was analyzed in a
      prospective way. The following variables were specifically recorded: age, weight,
      body mass index (BMI), waist circumference, and waist-to-hip ratio. Basal
      glucose, insulin, and TSH (thyroid-stimulating hormone) were measured. An
      indirect calorimetry and a tetrapolar electrical bioimpedance were performed. REE
      measured by indirect calorimetry was compared with REE obtained by prediction
      equations to obese or nonobese patients. RESULTS: The mean age was 44.8 +/- 16.81
      years and the mean BMI 34.4 +/- 5.3. Indirect calorimetry showed that, as
      compared to women, men had higher resting energy expenditure (REE) (1,998.1 +/-
      432 vs. 1,663.9 +/- 349 kcal/day; p < 0.05) and oxygen consumption (284.6 +/-
      67.7 vs. 238.6 +/- 54.3 ml/min; p < 0.05). Correlation analysis among REE
      obtained by indirect calorimetry and REE predicted by prediction equations showed
      the next data; Berstein's equation (r = 0.65; p < 0.05), Harris Benedict's
      equation (r = 0.58; p < 0.05), Owen's equation (r = 0.56; p < 0.05), Ireton's
      equation (r = 0.58; p < 0.05) and WHO's equation (r = 0.57; p < 0.05). Both the
      Berstein's and the Ireton's equations overpredicted REE and showed nonsignificant
      mean differences form measured REE. The Owen's, WHO's, and Harris Benedict's
      equations underpredicted REE. Our male prediction equation was REE = 58.6 + (6.1
      x weight (kg)) + (1,023.7 x height (m)) - (9.5 x age). The female model was REE =
      1,272.5 + (9.8 x weight (kg)) - (61.6 x height (m)) - (8.2 x age). Our prediction
      equations showed a nonsignificant difference with REE measured (-3.7 kcal/day)
      with a significant correlation coefficient (r = 0.67; p < 0.05). CONCLUSION:
      Previously developed prediction equations overestimated and underestimated REE
      measured. WHO equation developed in normal weight individuals provided the
      closest values. The two new equations (male and female equations) developed in
      our study had a good accuracy.

PMID- 16407646
TI  - Differential effects of cooked beans and cooked lentils on protein metabolism in
      intestine and muscle in growing rats.
AB  - AIMS: The effect of diets based on cooked beans or lentils on protein metabolism
      in intestines and muscles was studied in rats. METHOD: The cooked seeds were used
      as the unique protein source in balanced diets (containing 229 and 190 g of crude
      protein per kg dry matter) fed to young growing rats for 20 days. Their effects
      were compared with those of the control casein diet in pair-fed rats. Protein
      synthesis rates in small and large intestines and in gastrocnemius and soleus
      muscles were determined in vivo, in a fed state, by the flooding dose method,
      using 13C-valine. RESULTS: In the small and large intestine tissues of the legume
      fed groups, protein, RNA relative masses (mg.100 g BM(-1)) and protein synthesis
      rates (FSR and ASR) were higher than in the control rats (p < 0.05). In
      gastrocnemius and soleus muscles,protein and RNA contents (in mg) and protein
      synthesis rates were significantly (p < 0.05) lower in the legume-fed groups than
      in the control rats. CONCLUSION: The chronic intake of cooked legumes increased
      protein synthesis rates in intestinal tissues and decreased them in muscles. This
      effect was greater for beans than for lentils in the large intestine and in
      gastrocnemius muscle.

PMID- 16407647
TI  - Hand strike-induced hemolysis and adaptations in iron metabolism in Basque ball
      players.
AB  - INTRODUCTION: Basque ball players (BBPs) make repeated hand strikes to the ball
      which involves continuous mechanical trauma. OBJECTIVE: The aim of this work is
      to describe the hematological variations and changes in iron metabolism occurring
      in BBPs as a result of acute and continuous practice of this special sport native
      to Northern Spain. METHODS: 40 healthy male subjects volunteered to participate
      in this study: 11 subjects who exercise moderately (control group) but do not
      play Basque ball sport and 29 professional BBPs were studied in two situations:
      before a match (BM group) and after a match (AM group). The following
      hematological parameters were determined: red blood cell count (RBC), hemoglobin
      and hematocrit; MCV, MCH and MCHC. The following variables were measured in
      serum: iron, ferritin, transferrin, transferrin saturation, proteins, and lactate
      dehydrogenase (LDH). Proteins and hemoglobin were determined in urine. RESULTS:
      The BM group showed lower hematocrit, MCV, hemoglobin and serum transferrin
      levels, and higher LDH than controls. The AM group showed higher RBC, hemoglobin,
      serum proteins, iron, transferrin and LDH levels, lower plasma volume, and higher
      urine hemoglobin and protein levels than the BM group. CONCLUSIONS: Basque ball
      playing induces hemolysis and increases the plasma capability to quench free
      iron, but its clinical consequences on iron metabolism do not seem to be enough
      to take an iron intake proportional to the caloric intake. In order to prevent,
      in the long term, the development of anemia in these peculiar sportsmen, it would
      be useful that medical teams observe urine blood losses and oxidative stress in
      these BBPs.

PMID- 16407648
TI  - Fatty acid alterations in liver peroxisomes from n-3-deficient mice.
AB  - A diet deficient in n-3 fatty acids dramatically reduces docosahexaenoic acid
      (4.8-fold) and 20:5n-3 content in murine total peroxisomal phospholipids, and
      conversely increases 22:5n-6 (17.1-fold) and also, to a lesser extent, 20:4n-6.
      This was also found in purified phosphatidylethanolamine and phosphatidylcholine.
      After changing the non-deficient diet (containing alpha-linolenic acid, ALA) to a
      deficient one (deficient in ALA), it took a very long time for docosahexaenoic
      acid concentration in peroxisomes to decline (>5 months). In contrast, after
      changing the deficient to a non-deficient diet, time to complete recovery was
      more rapid (3 weeks). Changes in 20:5n-3, 22:6n-3 and 20:4n-6 were generally
      stabilized within 2-4 weeks. Dietary n-3 fatty acids control the fatty acid
      composition of peroxisomal membranes, and thus possibly affect some of their
      functions.

PMID- 16407649
TI  - Diacylglycerol-enriched structured lipids containing CLA and capric acid alter
      body fat mass and lipid metabolism in rats.
AB  - OBJECTIVE: The present study compared the effect of corn oil, diacylglycerol (DG)
      oil, and DG-enriched structured lipids (SL-DG) produced from corn oil, capric and
      conjugated linoleic acid on adiposity in rats fed an AIN-76 diet (5% fat) for 6
      weeks. METHODS: The plasma and hepatic lipids, adipose tissue weight, and enzyme
      activities related to fatty acid metabolism were determined. RESULTS: The weights
      of the epididymal white adipose tissue (WAT), perirenal WAT, and interscapular
      WAT were significantly lower in the SL-DG group than in the DG group. Reduction
      of fat mass in the SL-DG group was related to suppressing fatty acid synthase
      activities and enhancing beta-oxidation activity in perirenal WAT. The plasma
      leptin was lower in the SL-DG group than in the DG group, plus a lower plasma TG
      level was accompanied by an increase in adipocyte LPL activity. Meanwhile the SL
      DG supplement lowered the plasma and hepatic cholesterol level. In addition, the
      hepatic HMG-CoA reductase and ACAT activities were significantly lower in the SL
      DG group than in the other groups. CONCLUSION: The DG-enriched SL used in this
      study was effective in enhancing triglyceride metabolism in adipose tissue,
      especially as regards reducing the abdominal fat mass and cholesterol metabolism
      in the liver.

PMID- 16407651
TI  - The original Interleukin Hypothesis concerning inflammation as a complication of
      ESRD therapy.

PMID- 16407650
TI  - Excess casein in the diet is not the unique cause of low-grade metabolic
      acidosis: role of a deficit in potassium citrate in a rat model.
AB  - This study examined the effects of a dietary model of protein excess and K anion
      salt deficit on the occurrence of metabolic acidosis in rat. Rats were adapted to
      diets containing either 13 or 26% casein, together with mineral imbalance,
      through lowering K/increasing sodium/omitting alkalinizing anions. For each
      protein level, a group of rats was supplemented with K citrate. Dietary K citrate
      resulted in neutral urinary pH, whatever the protein level. Urea excretion was
      higher in rats adapted to 26% casein than 13% casein diets, but K citrate
      enhanced this excretion and suppressed ammonium elimination. No citraturia could
      be observed in acidotic rats, whereas K citrate greatly stimulated citraturia and
      2-ketoglutarate excretion. In conclusion, low-grade metabolic acidosis can occur
      with a moderate protein level in the diet. K citrate was apparently less
      effective in rats adapted to the 26% casein level than in those adapted to the
      13% casein level with regard to magnesium, citrate and 2-ketoglutarate
      concentrations in urine.

PMID- 16407653
TI  - Functional Vitamin E deficiency in ApoE4 patients with Alzheimer's disease.
AB  - Oxidative stress has been implicated in the development of Alzheimer's disease
      (AD). Consequently, antioxidant therapies including Vitamin E (VitE)
      supplementation for both prevention and treatment of neurodegenerative diseases
      currently appears to be a promising avenue of research. The aim of the present
      study was to examine the relationship between AD and the ApoE phenotype, lipid
      parameters and VitE levels in a large cohort of elderly subjects. No absolute
      deficit was observed in plasma VitE levels. However in AD, ApoE4 is not
      associated with an increase in total cholesterol (TC) and VitE levels. Moreover,
      our results suggest that oxidative stress-induced injury and protection by VitE
      in AD are related to the ApoE phenotype. Our study strongly supports the
      hypothesis of an impairment of lipophilic antioxidant delivery to neuronal cells
      in AD leading to a tissular antioxidant deficiency which could facilitate
      oxidative stress.

PMID- 16407654
TI  - Insulin resistance is an intrinsic defect independent of fat mass in women with
      Turner's syndrome.
AB  - BACKGROUND/AIMS: Turner's syndrome (TS) is associated with increased insulin
      resistance and adiposity, which might be associated with type 2 diabetes in later
      life. We aimed to determine whether the defect in insulin sensitivity is a
      primary intrinsic defect in TS or dependent on variation in body composition.
      METHODS: Sixteen women with TS not on growth hormone replacement but receiving
      oestrogen replacement therapy [age (mean +/- SD): 30.2 +/- 8.5 years; height
      corrected fat-free mass: 26.1 +/- 3.1 kg/height] and a control group of 16 normal
      healthy women (age: 30.1 +/- 8.2 years; height-corrected fat-free mass: 25.9 +/-
      2.4 kg/height) were studied. Fasting blood samples were obtained for measurement
      of glucose, insulin, IGF-I, IGFBP-1, IGFBP-3 and lipid levels. The
      hyperinsulinaemic euglycaemic clamp was performed to assess peripheral insulin
      sensitivity (M value), and the Homeostasis Model Assessment (HOMA-S) was used to
      estimate fasting insulin sensitivity. Body composition was assessed using a dual
      energy X-ray absorptiometry scan. RESULTS: Fasting insulin sensitivity (HOMA-S
      103.2 +/- 78.6 vs. 193.9 +/- 93.5, p = 0.006) was lower in TS subjects compared
      to controls as was whole-body insulin sensitivity (M value 2.9 +/- 1.9 vs. 5.5 +/
      2.6 mg/kg/min, p = 0.003). In a multiple regression analysis the Turner
      karyotype was significantly related to insulin sensitivity (p = 0.008)
      independent of any differences in fat-free mass and percent whole-body fat mass.
      CONCLUSION: The increased insulin resistance in women with TS is independent of
      measures of body composition and may represent an intrinsic defect related to
      their chromosomal abnormality.

PMID- 16407655
TI  - Variation of host cell tropism of porcine endogenous retroviruses expressed in
      chinese Banna minipig inbred.
AB  - A serious donor-organ shortage urges the use of animal donors to treat a wide
      appropriate variety of major health problems including organ failure and
      diabetes. However, the promise of clinical xenotransplantation is offset at the
      present time by the potential of a public health risk due to the cross-species
      transmission of pathogens from animal donors to human patients. In particular,
      the transmission of porcine endogenous retrovirus (PERV) is a major concern. In
      this study, cell tropism of PERV was tested by in vitro infection of human
      primary cells and cell lines. Coculture of PERV supernatant derived from PK15
      with human primary cells and cell lines resulted in the transfer and expression
      of PERV-specific sequences and the establishment of a productive infection. In
      the detection of tropism variation of PERV in pigs, 293 cells were cocultured
      with mitogenic-activated and lethally irradiated PBMC from 12 Banna minipig
      inbred (BMI). The results were that six coculture groups were PERV-positive.
      However, infectious virus was not detected when activated PBMC from the other 7
      pigs were cocultivated with human cells known to be permissive for PERV, which
      indicated a tropism variation among the tested individuals. All these findings
      demonstrate that the presence of endogenous viruses in source animals needs to be
      carefully considered when the infectious disease potential of xenotransplantation
      is being assessed.

PMID- 16407656
TI  - Quantitative analysis of viral RNA in the murine heart and pancreas with
      different concentration of coxsackievirus B3.
AB  - OBJECTIVES: We investigated the clinical features, pathologic changes, and viral
      RNA kinetics in the course of acute and subacute experimental coxsackievirus B3
      (CVB3) infection in a murine model. METHODS: Five-week-old A/J inbred male mice
      were divided into 5 groups. Four of those groups were inoculated
      intraperitoneally with 5 x 10(4) (group 1), 1 x 10(5) (group 2), 5 x 10(5) (group
      3), or 1 x 10(6) (group 4) PFU of CVB3. Control mice were inoculated with
      uninfected Vero cell lysate in DMEM. Mice from each group were sacrificed on days
      7 or 14 after inoculation. RESULTS: Bloody diarrhea, earlier weight loss,
      perianal swelling, and death were correlated with higher viral load. One of ten
      mice in group 3 and 5 of 10 mice in group 4 died spontaneously between days 4 and
      12 after inoculation. All of the remaining 34 mice of infected groups
      demonstrated extensive pancreatic inflammation. Focal myocarditis developed in
      only 4 (11.8%) of those 34 subjects. Amylase and creatine kinase activities in
      the serum were increased in the mice of infected groups. CVB3 RNA was detected in
      the heart and pancreatic tissue in all subjects. The CVB3 RNA copy number in
      pancreatic tissue was not correlated with the severity of inflammation.
      CONCLUSIONS: In the murine model, viral loading dose determines the clinical
      features of CVB3-induced infection, and the severity of pancreatitis is not
      correlated with the viral loading dose or tissue level of viral RNA. .

PMID- 16407657
TI  - Clinical significance of the genotype and core promoter/pre-core mutations in
      hepatitis B virus carriers.
AB  - It has been shown that clinical and virological characteristics vary among
      hepatitis B virus (HBV) genotypes. In this study, we measured the virus level,
      disease severity, and presence or absence of core promoter (CP)/pre-core (PC)
      mutations in 241 HBV carriers, and investigated the clinical significance of
      measuring the HBV genotype. In genotype C HBV carriers, the proportion of
      hepatitis B e antigen (HBeAg)-positive patients was significantly higher than
      that in genotype B HBV carriers (0 vs. 34.4%, p < 0.05), and the virus level was
      higher (4.9 vs. 4.05 LGE/ml). In the genotype B HBV carriers, the incidence of PC
      mutation was significantly higher (69 vs. 34%, p < 0.05). In the genotype C HBV
      carriers, the incidence of CP mutation was significantly higher (13 vs. 78%, p <
      0.05). We compared patients with the wild (W)/mutant (M) pattern in the CP/PC
      regions to those with the M/W pattern in the CP/PC regions among the genotype C
      HBV carriers. Both the proportion of HBeAg-positive patients (65.8 vs. 15.4%, p <
      0.05) and the alanine aminotransferase (ALT) level (48 vs. 21.5 IU, p < 0.05)
      were higher in the patients with the M/W pattern in the CP/PC regions, and the
      disease severity was deteriorated. In conclusion, genotype B HBV may more
      frequently induce HBe seroconversion via PC mutation compared to genotype C HBV.
      Among the genotype C HBV carriers, hepatitis activity and the deterioration of
      the disease severity were significantly inhibited in the group in which PC
      mutation initially occurred, in comparison to the group in which CP mutation
      initially occurred.

PMID- 16407658
TI  - Genome-based phylogeny of poxvirus.
AB  - A comprehensive phylogenetic analysis of Poxviridae was performed in this study.
      Phylogenetic trees were reconstructed from whole genomic information including
      gene order, gene content, and all conserved gene protein sequences. Gene content
      and gene order were the methods used for the first time in cladogram
      reconstruction of poxvirus. The results of the different methods finally shared
      mainly consistent tree topologies, which were supported by the classic taxonomy
      of Poxviridae. According to these topologies, the Entomopoxvirinae and
      Chordopoxvirinae subfamilies are divergent from each other. Subfamily
      Chordopoxvirinae could be divided into four main groupings, which could be
      further divided into subgroups. Parapoxvirus and Molluscipoxvirus have been
      considered distinct from other Chordopoxvirus. Results from our study
      consistently supported this suggestion. In our results, Parapoxvirus and
      Molluscipoxvirus were the most closely related genera and formed a group. This
      group could be the one that branched after the divergence of Avipoxviruses.
      Additionally, rabbitpox virus and vaccinia virus steadily formed clusters with
      high bootstrap support in all the cladograms.

PMID- 16407659
TI  - Skin-derived micro-organs induce angiogenesis in rabbits.
AB  - We have recently reported an alternative cell therapy approach to induce
      angiogenesis. The approach is based on small organ fragments--micro-organs (MOs)-
      whose geometry allows preservation of the natural epithelial/mesenchymal
      interactions and ensures appropriate diffusion of nutrients and gases to all
      cells. We have shown that lung-derived MOs, when implanted into hosts, transcribe
      a wide spectrum array of angiogenic factors and can induce an angiogenic response
      that can rescue experimentally induced ischemic regions in mice. From a clinical
      perspective, skin-derived MOs are particularly appealing as they could readily be
      obtained from a skin biopsy taken from the same target patient. In the present
      work we have investigated the angiogenesis-inducing capacity of rabbit and human
      skin-derived micro-organs in vitro and in vivo. Rabbit skin MOs were implanted
      into homologous adult rabbits and human skin MOs were encapsulated and implanted
      into xenogenic mice. Skin-derived MOs, as lung-derived MOs, were found to secrete
      a whole array of angiogenic factors and to induce a powerful angiogenic response
      when implanted back into animals. We believe the approach presented suggests a
      novel, efficacious and simple approach for therapeutic angiogenesis.

PMID- 16407660
TI  - New insight into abnormal muscle vasodilatory responses in aged hypertensive rats
      by in vivo nuclear magnetic resonance imaging of perfusion.
AB  - OBJECTIVE: Increased peripheral arterial resistances and decreased maximum
      vasodilation are characteristic features of chronic hypertension. However, little
      data are available in the literature regarding the possible alterations in the
      temporal patterns of vasodilatory responses elicited by various stimuli. DESIGN:
      This question was addressed by measuring skeletal muscle perfusion using nuclear
      magnetic resonance imaging combined with arterial spin labeling. METHODS: Ninety
      week-old male spontaneously hypertensive (SHR; n = 7) and normotensive Wistar
      Kyoto (WKY; n = 8) rats were studied, and calf muscle perfusion was measured at
      rest and during reactive hyperemia following total ischemia of 5 and 30 min
      duration. RESULTS: Reactive hyperemia profiles differed according to duration of
      ischemia. In WKY rats, 5 min of ischemia induced a short peak of hyperemia
      lasting no more than 63 s, while 30 min of ischemia were followed by a prolonged
      hyperemic response of 261 s. In SHRs, after 5 min of ischemia, peak muscle
      arterial conductance was decreased to 0.5 +/- 0.3 versus 0.9 +/- 0.3 ml.min(
      1).100 g(-1).mm Hg(-1) in the WKY rats (p < 0.05), as expected. After 30 min of
      ischemia, there was, in addition, a shortening of the hyperemic response
      duration. Time to post-ischemic half normalization of arterial conductance was 38
      +/- 24 s in the SHRs versus 149 +/- 58 s in the WKY rats (p < 0.001). CONCLUSION:
      In vivo perfusion measurement not only confirmed the existence of a reduced
      maximum peripheral vasodilation in chronically hypertensive rats, it revealed a
      blunted hyperemic response after prolonged ischemia in the SHRs, which might be
      an important contributing factor to the increased sensitivity to ischemia in
      hypertension.

PMID- 16407661
TI  - Serum starvation and growth factor receptor expression in vascular smooth muscle
      cells.
AB  - BACKGROUND: Smooth muscle cell (SMC) proliferation in atherosclerosis is
      regulated through the interaction of growth factors like platelet-derived growth
      factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) and their receptors
      (R). We hypothesized that serum starvation of SMCs may affect PDGFbeta-R and IGF
      1-R expression and, consequently, the effect of their cognate ligands on SMC
      survival/proliferation. METHODS AND RESULTS: Serum starvation significantly
      increases PDGFbeta-R but not IGF-1-R mRNA and protein expression in SMCs. PDGF-BB
      stimulates cell survival but not proliferation in serum-starved SMCs of the
      synthetic phenotype, whereas SMCs of the contractile phenotype respond to PDGF-BB
      by a significant increase in proliferation. Immunohistochemical analysis of
      coronary atherosclerotic lesions reveals PDGFbeta-R expression in SMCs in the
      lamina fibromuscularis, but not in the media and in healthy parts of the arterial
      wall. No such differential expression was observed for IGF-1-R. CONCLUSIONS:
      Differential regulation of PDGFbeta-R and IGF-1-R expression by serum starvation
      might represent a mechanism for the control of SMC survival/proliferation in
      atherogenesis and restenosis. The distribution of PDGFbeta-Rs and IGF-1-Rs in
      atherosclerotic lesions may indicate an effect of serum starvation on SMCs in the
      arterial wall.

PMID- 16407662
TI  - Evaluation of the time course of vascular responses to venous congestion in the
      human lower limb.
AB  - This study examined the time course of changes in blood flow to the lower leg in
      response to venous distension--the veni-arteriolar vasoconstrictor response--in
      31 healthy males. During a 5-min period of venous distension (thigh cuff pressure
      50 mm Hg), calf blood flow (venous occlusion plethysmography) decreased more
      rapidly (within 30 s) compared to skin perfusion (after 2 min, Laser Doppler
      flowmetry), consistent with disparate filling times of superficial and deeper
      veins and a greater increase in deep vein volume. On completion of venous
      filling, vascular resistance in the skin was unchanged from baseline, implying
      that the reduction in perfusion was solely the result of reduced perfusion
      pressure. For the whole calf, vascular resistance was unchanged after 1 min but
      decreased thereafter by 35-45% from baseline, indicating adjustment of pre- or
      post-capillary resistances to maintain flow. Repeated plethysmographic flow
      measurements assisted the decrease in resistance, most likely by intermittent
      compression of the thigh cuff acting to displace blood volume centrally and
      alleviate congestion. These findings do not support an active veni-arteriolar
      vasoconstrictor mechanism in response to venous distension alone in the lower
      leg, and provide evidence of dynamic flow adjustments that should be acknowledged
      during procedures that involve prolonged periods of venous congestion.

PMID- 16407663
TI  - [Clinical strategy for management and prevention of allergic diseases--from the
      viewpoint of diagnosis, treatment, management of asthma].

PMID- 16407664
TI  - [Allergy and autoimmunity mediated by IgG and Fcgamma receptors].

PMID- 16407666
TI  - [Provision against food allergy in the school lunch program in Japan].
AB  - BACKGROUND: We speculated that 130000 students suffer from food allergy in Japan.
      We have had no information about food allergy students at school diet. METHOD:
      The Aggregate Corporation of All Japan School Dietician Conference cooperated
      with our investigation. We sent a questionnaire by mail to all school dieticians
      who belong with the conference. RESULT: We could collect up 10190 cooking place
      and 8035306 students. The cooking places which didn't investigate food allergy
      accounted for 1031 facilities. Although food allergy children were in the school,
      the cooking place which didn't take measures to prevent food allergy in school
      diet accounted for 1031 facilities. 5476 cooking places supplied school diet
      which managed food allergy students. But alterative school diet was supplied only
      2122 cooking places. CONCLUSION: We could know current state of food allergy in
      school diet. We must develop to take measure against food allergy accidents at
      the school diet for food allergy students.

PMID- 16407665
TI  - [Additive effect of intravenous prednisolone for acute severe asthma in infants
      and toddlers: a randomized controlled clinical trial].
AB  - BACKGROUND: The efficacy of systemic corticosteroids for infants and toddlers
      with acute severe asthma has been inadequately evaluated. OBJECTIVE: The purpose
      of this study was to evaluate the additive efficacy of intravenous prednisolone
      in a randomized controlled study in the management of infants and toddlers with
      acute severe asthma. METHODS: Sixty-two patients (aged 8 to 70 months)
      hospitalized with status asthmaticus were studied. They were randomized into two
      groups. One group received intravenous prednisolone treatment (1 approximately 3
      mg/kg/day, 3 days); the other group served as a control. Each group received
      continuous aminophylline infusion and low-dose continuous isoproterenol
      inhalation by an Inspiron nebulizer. They were monitored their heart rate,
      respiratory rate and symptoms (Wood's clinical score). RESULTS: Each group showed
      rapid improvement in heart rate, respiratory rate and clinical score by low-dose
      continuous isoproterenol inhalation. There were no significant differences in the
      time course of these clinical indexes or the duration of aminophylline infusion,
      continuous isoproterenol inhalation and hospital stay. CONCLUSION: This study
      failed to confirm the additive benefit of intravenous prednisolone in the
      management of infants and toddlers with acute severe asthma.

PMID- 16407667
TI  - [Wheat anaphylaxis enhanced by administration of acetylsalicylic acid or by
      exercise].
AB  - A 23-year-old woman experienced generalized urticaria and loss of consciousness
      during walking after ingestion of wheat. Skin prick test and CAP-RAST were
      positive for gluten. An oral challenge test using 100g wheat was positive without
      exercise. The patient was given diagnosis of wheat allergy. In addition, not only
      exercise but also administration of 500mg aspirin were found to exacerbate her
      symptoms after the ingestion of wheat, suggesting that acetylsalicylic acid could
      be an augmentation factor in wheat allergy. Etodorac failed to enhance the
      symptoms. Further, oral administration of Fexofenadine could prevent allergic
      reactions induced by ingestion of 100g wheat, but sodium cromoglycate partially
      reduced the reactions.

PMID- 16407668
TI  - [Case of congestive heart failure associated with hypereosinophilia developed
      during antibiotics treatment].
AB  - A 92-year-old man with a history of bronchial asthma and allergic rhinitis
      received antibiotics for sepsis by methicillin-resistant Staphylococcus aureus
      and multidrug-resistant Enterococcus gallinarum. During the antibiotics
      treatment, skin eruptions, liver dysfunction, and hypereosinophilia developed,
      followed by dyspnea, congestive heart failure, electrocardiographic
      abnormalities, and diffuse mild myocardial hypokinesis. After the discontinuation
      of the antibiotics and the administration of steroid, skin eruptions, liver
      dysfunction, and hypereosinophilia improved parallel with the improvement of the
      congestive heart failure. Vancomycin hydrochloride and teicoplanin were suspected
      as the causative drugs on the basis of the treatment course. Although congestive
      heart failure is rare in the case of drug-induced hypereosinophilia, it is one of
      life-threatening complications. We describe herein a case of congestive heart
      failure associated with hypereosinophilia developed during antibiotics treatment,
      successfully treated with steroid after the discontinuation of the causative
      drug.

PMID- 16407669
TI  - [Allergic inflammation and immune response: role of cytokine].

PMID- 16407670
TI  - [Ocular involvement in clinical management of allergology].

PMID- 16407671
TI  - [The assessment and treatment for psychological aspect in allergic diseases].

PMID- 16407672
TI  - [Quality of life of asthmatic children and their guardians--multi center study in
      Kyusyu and Okinawa, Japan].
AB  - BACKGROUND: It is important to clarify the quality of life (QOL) of the asthmatic
      children and their guardians. METHOD: We studied asthmatic patients treated at
      359 institutes in Kyusyu and Okinawa, Japan, with QOL questionnaire 2 times in
      2001. In the first study, 2906 patients were recruited and 2935 patients were in
      the 2nd study, and 1563 patients were in both study. RESULT: There was a
      statistically significant relationship, between the QOL and the clinical symptoms
      in the last 2 weeks, between the QOL and the severity of asthmatic symptoms, and
      between the patients' or their guardians' QOL and recognition of symptoms. There
      was a statistically significant relationship between the QOL answered by patients
      and those by guardians. More significant relationship of QOL between patients'
      and guardians' was seen in the patients with asthmatic attack or in the severe
      group, especially in schoolchildren. CONCLUSION: Asthmatic control is important
      for improvement of QOL. Because correlation is significant in QOL between parent
      and child especially in schoolchildren, asthmatic control is particularly
      important.

PMID- 16407673
TI  - [Prediction of atmospheric Japanese cedar pollen counts in Oita University
      Faculty of Medicine Complex].
AB  - BACKGROUND: We investigated the method of predicting atmospheric Japanese cedar
      pollen counts and the first day of pollen release at Oita University Faculty of
      Medicine Complex in this study. METHOD: We set up a Durham sampler on the roof
      (30 m from the ground) of Oita University Faculty of Medicine complex and
      investigated atmospheric pollen counts day by day from January 1 to April 30 from
      1990 through 2004. RESULTS: The total pollen counts per year correlated very well
      with averaged temperature, averaged relative humidity, and the sunshine duration
      during the previous July. The sunshine duration yielded the highest correlation
      coefficient. Multiple regression analysis showed the sunshine duration during the
      previous July and total pollen count of the previous year to be independent
      predictors of the current year's total pollen counts. Multiple correlation
      coefficients was 0.9518 (p<0.001). We considered the Hita area to be the source
      of the pollen, according to meteorological conditions. Prediction of total pollen
      counts was more accurate if based on factors within the previous 10 years than on
      factors within the previous 5 years. There was no correlation between the first
      day of pollen release and averaged temperature in January. Our data also showed
      that the first day of pollen release could not be predicted by the cumulative
      thermal constant method and threshold temperature for the development of male
      Japanese cedar flowers. Multiple regression analysis showed the minimum
      temperature from November 1 to the first day of pollen release, the date of
      minimum temperature, and the averaged temperature for the January to be
      independent predictors of the number of days from January 1 to the first day of
      pollen release. CONCLUSION: We concluded that it is important to establish a
      method of predicting atmospheric Japanese cedar pollen counts that is based on
      the characteristics of each area.

PMID- 16407674
TI  - [Three cases of centipede allergy--analysis of cross reactivity with bee
      allergy].
AB  - BACKGROUND: We experienced three cases of patients who suffered from systemic
      urticaria and systemic symptoms such as general fatigue and dyspnea which
      occurred just after the sting of centipede. The result of prick test by centipede
      venom revealed positive reaction in all three patients, so we diagnosed the
      symptoms of them as immediate type allergic reaction against centipede venom. And
      more there have been some reports documented the relationship between centipede
      allergy and bee allergy, so we added the examination about bee allergy on these
      three patients. METHODS: The measurement of bee venom specific IgE was practiced
      on all three patients and intradermal skin test about bee venom was done only on
      one patient. Moreover we also practiced prick test of centipede venom against
      another three patients who were diagnosed as having bee allergy. RESULTS: All
      patients of centipede allergy showed positive reaction for the specific IgE
      antibody of Wasp and/or Honeybee and one patient who was practiced skin test also
      reacted positively against Wasp and Yellow Jacket venom. But none of three
      patients of bee allergy showed positive reaction against centipede venom.
      CONCLUSION: According to these results we suspected that there lies some
      relationship between centipede allergy and bee allergy. But it is supposed that
      only little involvement of centipede allergy was concerned among the patients of
      bee allergy. Until now there have been only a few reports as to the centipede
      allergy. But actually we guess it may be the phenomenon that could occur
      frequently.

PMID- 16407675
TI  - [Antigenic analysis of patients with asthma contracting by exposure to different
      species of pet hamsters].
AB  - BACKGROUND: Hamster-specific IgE antibodies as measured by currently available
      CAP-RAST tests are used to diagnose allergies associated with exposure to pet
      hamsters. Among patients with asthma attributed to hamsters, only about 60% are
      positive for hamster-specific IgE antibodies. We examined whether the results of
      CAP-RAST tests are related to differences in species-related antigens. METHODS:
      Currently available mixed specific IgE antibodies against European hamster and
      Golden hamster antigens (e84) were combined with Djungarian hamster epidermis to
      produce 3-species mixed specific antibodies. Correlations between results
      obtained with these mixed antibodies, those obtained with e84 and Djungarian
      hamster specific IgE antibody were examined in 20 patients with asthma who kept
      hamsters as pets. In addition, immunoblotting was used to analyze antigens in 9
      patients. RESULTS: There was no correlation between results obtained with e84 and
      those obtained with Djungarian hamster antibody. Results obtained with 3-species
      mixed specific IgE antibodies positively correlated with those obtained with
      Djungarian hamster antibody. A specific binding protein for 67-kDa protein were
      found in patients who tested positive for e84 and Djungarian hamster antibody. A
      specific binding protein for 20-kDa protein were found in patients positive for
      only Djungarian hamster antibody. CONCLUSION: The main allergens differ among
      Golden hamsters, European hamsters, and dwarf Djungarian hamsters.

PMID- 16407676
TI  - [A case of severe persistent bronchial asthma who showed significant improvement
      by switching to hfa-bdp, with reducing the dosage of oral steroids].
AB  - A case, 54-year-old female teacher, has been treated for severe persistent asthma
      mainly with an inhaled corticosteroid, budesonide (BUD), 600 microg/day. The
      higher dose was considered inappropriate due to the adverse effects including
      hoarseness, thus, prednisolone (PSL) was frequently given when needed. In this
      situation, administration of hydrofluoroalkane-beclomethasone dipropionate (HFA
      BDP), 400 microg/day, was started instead of BUD, and then improvement of the
      clinical symptoms, PEF and pulmonary function were observed promptly, followed by
      reduction in the dosage of PSL and a short-acting beta-stimulant. With higher
      doses of HFA-BDP, her pulmonary condition improved more remarkably. The levels of
      ECP, Eotaxin and RANTES in induced sputum obtained by inhalation of 10%
      hypertonic saline were measured prior to the medication change and after one
      year, and all of the levels were found to be decreased, from 19000 to 96.0
      microg/L, from 410 to 319 pg/ml, and from 281 to 85.1 pg/ml, respectively,
      indicating improvement of the condition. The overall score of Asthma Quality of
      Life Questionnaire by Juniper also improved from 5.3 to 6.6 points after one
      year. In this case study, it was suggested that HFA-BDP may reduce eosinophilic
      inflammation remained in the peripheral airway, and may be effective in
      supplementing the activity of PSL which must be taken orally by severe asthmatic
      patients.

PMID- 16407677
TI  - [Allergy and gene].

PMID- 16407679
TI  - [Toll-like receptors and its regulation].

PMID- 16407678
TI  - [New diagnostic radiology of airway disease in patients with asthma and chronic
      obstructive pulmonary disease].

PMID- 16407680
TI  - [Four cases of pollen-food allergy syndrome suspected the cross reactivity
      including latex].
AB  - BACKGROUND: Generally it is recognized that the occurrence of fruit allergy is
      attributed not to the sensitization of itself but to the cross reactivity with
      pollens or latex. But the relationship as to the sensitization between pollen and
      latex is obscure. So we aimed to investigate the relation of sensitization among
      pollens, fruits and latex. METHODS: We tried to examine latex-specific IgE titer
      and practice skin prick test of latex for the patients of pollen-food allergy
      syndrome. RESULTS: It was confirmed that some patients of pollen-food allergy
      syndrome showed positive reactions against both specific IgE and skin prick test
      of latex, though they could tolerate latex products in their daily lives. We
      present here four patients of such clinical courses concretely. CONCLUSION: The
      patients of pollen-food allergy syndrome should be practiced examination about
      latex allergy, even if they can use latex products without any symptoms. And more
      if positive results are obtained, additional examination such as immunoblot and
      IgE RAST inhibition test are recommended to practice in order to clarify the
      unresolved problems, such as 1) which factor is the major allergen to cause cross
      reactivity among these three factors? 2) what occurs if patients of same clinical
      courses with our cases continue to use latex products? Further investigation will
      be indispensable to resolve these problems in the future.

PMID- 16407681
TI  - [A case of anaphylaxis caused by the health food chitosan].
AB  - Chitosan is a linear polysaccharide with about 10(5)-10(6) molecular weight
      existing in cell walls of zygomycetes. Chitosan decreases serum neutral fat and
      cholesterol levels and has dietary fiber action, and many products have recently
      been sold as health foods. Here, we report a case of immediate-type allergy for
      chitosan-containing health food with a review of the literature. The patient was
      a 47-year-old female person who developed systemic urticaria and difficulty in
      breathing after oral ingestion of chitosan. Since skin tests (prick test and
      scratch patch test) were positive, the test was done using another commercial
      chitosan, and was positive. The patient was diagnosed as having chitosan-induced
      immediately-type allergy, and was instructed to avoid ingestion of chitosan. The
      patient has developed no symptom thereafter. Regarding allergic reactions to
      chitin and chitosan, contact dermatitis induced by chitosan-containing cream has
      been reported from France and Portugal, but to our knowledge, there has been no
      report of immediate-type allergic reactions. Chitosan is a polysaccharide, not
      protein, but may have functioned as a food allergen because of its molecular
      weight and general properties.

PMID- 16407682
TI  - [Alternation of ion transport of airway epithelium by eicosanoids].
AB  - BACKGROUND: Airway surface liquid is thought to be regulated by the ion transport
      processes across the airway epithelium in a vectorial manner. Short circuit
      current (Isc) measured by Ussing chamber is an indication of electric
      permeability because of mutually related transportation of amount of ion between
      apical and basolateral membrane. METHODS: Guinea pig trachea was mounted on
      Ussing chamber and short-circuited current was determined continuously. After
      basolateral application of eicosanoids such as PGD2 and LTC4/LTD4/LTE4,
      Ramatroban, CRTH2 receptor antagonist and Pranlucast, LT receptor antagonist was
      added from basolateral side. A typical Cl-channel blocker, NPPB, was added from
      apical side. RESULTS: Isc were increased after basolateral application of
      eicosanoids. These effects were partly inhibited by each antagonist. Cl- channel
      blocker suppressed effects of each eicosanoids. CONCLUSION: Eicosanoids alter the
      ion transport mechanism via chloride channels on the airway epithelium that can
      be blocked by those antagonists.

PMID- 16407683
TI  - More confusing messages from the hypertension treatment trials.

PMID- 16407684
TI  - Characteristics and management of patients presenting to the emergency department
      with hypertensive urgency.
AB  - Few studies have examined the characteristics of patients presenting with
      hypertensive urgency, factors contributing to their presentation, or their
      management. The time and cost associated with treatment are unknown.
      Retrospective analysis of 50 emergency department patients with hypertensive
      urgency (symptomatic blood pressure (BP) elevation focusing on systolic BP >180
      mm Hg or diastolic BP >110 mm Hg) was performed. The hospital database was
      queried to determine the cost of the average treat-and-release visit. The mean
      age was 54.3+/-15.6 years; 64% were female; 46% were black; 90% had diagnosed
      hypertension. The mean presenting BP was 198+/-27.6/109+/-17.3 mm Hg; 66% had
      systolic BP >180 mm Hg, and 38% had diastolic BP >110 mm Hg. Initially, 30% were
      not on antihypertensives, and 28% were on monotherapy. Headache (42%) and
      dizziness (30%) were most frequently reported symptoms. Presentation was most
      often attributed to running out of medication (16%). IV and oral labetalol were
      given to 28% and 24% of patients, respectively. Fifty-six percent of patients had
      no change in baseline therapy at discharge. The average emergency department stay
      was 5 hours 17 minutes +/- 4 hours 27 minutes. The average cost for similar
      visits in 2004 was 1543 dollars per visit. Emergency department visits for
      hypertensive urgency are related mostly to noncompliance. Labetalol was the most
      frequently used therapy. Management in the primary care office could result in
      substantial cost savings.

PMID- 16407685
TI  - A meta-analysis of the effect of thiazolidinediones on blood pressure.
AB  - In epidemiologic studies, insulin resistance is associated with hypertension.
      Thiazolidinediones (TZDs) are antidiabetic agents that decrease insulin
      resistance. Multiple clinical trials have evaluated the effect of TZDs on blood
      pressure (BP) with inconsistent results. The aim of this study was to estimate
      the effect of TZDs on BP. The authors searched PubMed for clinical trials
      published in English. A total of 37 clinical trials that reported a change in BP
      were included in the analysis. Trials with independent-group design and trials
      with pre-post design were evaluated separately. When compared with baseline, TZDs
      lowered systolic BP by 4.70 mm Hg (95% confidence interval, -6.13 to -3.27) and
      diastolic BP by 3.79 mm Hg (95% confidence interval, -5.82 to -1.77). When
      compared with placebo, TZDs lowered systolic BP by 3.47 mm Hg (95% confidence
      interval, -4.91 to -2.02) and diastolic BP by 1.84 mm Hg (95% confidence
      interval, -3.43 to -0.25). Thus, TZDs lower both systolic and diastolic BP,
      albeit the BP-lowering effect is small and may not be of clinical significance.

PMID- 16407686
TI  - Attempted forced titration of blood pressure to <130/85 mm Hg in type 2 diabetic
      hypertensive patients in clinical practice: the diastolic cost.
AB  - The authors assessed the practicality and results of forced titrating of blood
      pressure to <130/85 mm Hg based on guidelines of the sixth Report of the Joint
      National Committee on Prevention, Detection, Evaluation, and Treatment of High
      Blood Pressure in the setting of a clinical practice in 257 diabetic,
      hypertensive patients. Goal diastolic pressure was achieved in 90% of the
      patients, but goal systolic pressure was achieved in only 33%. In 57% of the
      patients, the attained diastolic pressure was < or =70 mm Hg, and in 20% of the
      cohort diastolic pressure was reduced to <70 mm Hg (mean, 60+/-1 mm Hg). Patients
      with final diastolic pressure <70 mm Hg were older, had a higher prevalence of
      coronary artery disease, and higher initial systolic and pulse pressures compared
      with patients with final diastolic pressure of 71-85 mm Hg. Thus, attempted
      lowering of blood pressure to <130/85 mm Hg is associated with excessive lowering
      of diastolic pressure in a significant number of patients. Whether the benefits
      of tight systolic control outweigh the risks of excessive diastolic reduction
      requires further prospective assessment.

PMID- 16407687
TI  - Fibrates in combination with statins in the management of dyslipidemia.
AB  - While elevated low-density lipoprotein cholesterol is the primary target of
      hypercholesterolemia treatment, high triglycerides and low high-density
      lipoprotein cholesterol are also important targets for therapy. Correcting these
      lipid abnormalities should be an integral part of therapy in hypertensive
      individuals. Medications such as the fibrates are effective and well tolerated
      for reducing triglycerides and increasing high-density lipoprotein cholesterol,
      and their use has resulted in a reduction in cardiovascular events. Fibrates are
      also recommended as adjunct therapy for patients receiving statins whose low
      density lipoprotein cholesterol or non-high-density lipoprotein cholesterol is
      not reduced to goal levels. The combination of a statin and a fibrate may,
      however, raise the risk of myopathy and rhabdomyolysis. Gemfibrozil, one of the
      fibrates, but not fenofibrate, interferes with statin glucuronidation, which may
      increase the risk of myopathy due to elevations in statin serum levels. This may
      at least partially explain the lower incidence of myopathy with fenofibrate
      compared with gemfibrozil when combined with statins. Combination therapy with a
      fibrate and a statin is a potentially useful therapy for patients with
      atherogenic lipid profiles, for which fenofibrate appears to be a more
      appropriate choice due to less myopathic potential.

PMID- 16407688
TI  - The metabolic syndrome--what is it and how should it be managed?
AB  - Following a hypertension symposium in Portland, ME, in October 2005, a roundtable
      was convened to discuss the metabolic syndrome and its significance. Dr. Marvin
      Moser of the Yale University School of Medicine, New Haven, CT, moderated the
      discussion. Participating in the discussion were Dr. Bonita Falkner of the
      Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; Dr.
      Michael A. Weber of SUNY Downstate College of Medicine, New York, NY; and Dr.
      Leonard Mark Keilson of the University of Vermont College of Medicine.

PMID- 16407689
TI  - Challenges and risks in attaining the systolic blood pressure goal of <130 mm Hg
      in all diabetic patients.

PMID- 16407690
TI  - Pharmacotherapy review: calcium channel blockers.
AB  - As a drug class, calcium channel blockers encompass a heterogeneous group of
      compounds with distinctive structures and pharmacologic characteristics. These
      agents are widely used in the treatment of hypertension, chronic coronary
      ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding
      to increased cardiovascular risk associated with calcium channel blocker use has
      been silenced by an array of outcomes trials that show these drugs to be both
      safe and effective in reducing hard cardiovascular end points. The most common
      side effects associated with calcium channel blockers are vasodilatory in nature
      and include a non-volume-dependent form of peripheral edema, flushing, and
      headache. Despite the sometimes discomforting side effects seen with calcium
      channel blocker therapy, their robust blood pressure-lowering effect makes them
      an important component of most multidrug regimens used for blood pressure
      control.

PMID- 16407691
TI  - Now we are sick: labeling and hypertension.

PMID- 16407692
TI  - Hypertensive urgency.

PMID- 16407693
TI  - Analysis of recent papers in hypertension.

PMID- 16407694
TI  - Antihypertensive therapy and its effects on potassium homeostasis.
AB  - The role of potassium in cardiovascular disease and the importance of preserving
      potassium balance have emerged as clinical hot points, particularly as they
      relate to cardioprotective and renoprotective therapies that secondarily promote
      potassium retention. Antihypertensive medications that most commonly influence
      serum potassium levels and/or total body potassium include beta blockers and
      potassium-wasting and potassium-sparing diuretics as well as angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers. Uncertainty
      exists as to the best way to monitor potassium levels when any of these drug
      therapies are used, particularly in the setting of chronic kidney disease and/or
      heart failure. Guidelines for the monitoring of serum potassium levels in the
      setting of antihypertensive therapy are at best makeshift and often drawn from
      the know-how of the treating physician.

PMID- 16407696
TI  - Is hypertension a disease, and is it time to shift the paradigm?

PMID- 16407697
TI  - Ethnic differences in barriers and referral to cardiac rehabilitation among women
      hospitalized with coronary heart disease.
AB  - Important gender differences in cardiac rehabilitation utilization are well
      established, yet few studies have documented whether reported barriers and
      referrals vary by ethnicity. This is a cross-sectional study to determine whether
      barriers and referrals to participation in cardiac rehabilitation differed by
      race/ethnicity in 304 women (52% ethnic minorities) hospitalized with coronary
      heart disease. Nearly all subjects (92%) strongly agreed that physician referral
      was important to participation in rehab, but only 22% of subjects reported
      physician instruction to attend. Whites were more likely than minorities to
      report instruction to attend cardiac rehabilitation, and minorities were more
      likely to report financial barriers when compared with whites. These disparities
      need to be addressed because minority women have a worse prognosis following
      hospitalization for coronary heart disease, and cardiac rehabilitation has been
      shown to improve survival.

PMID- 16407698
TI  - Trait anger and arterial stiffness: results from the Atherosclerosis Risk in
      Communities (ARIC) study.
AB  - The cross-sectional association between trait anger and stiffness of the left
      common carotid artery was examined in 10,285 black or white men or women, 48-67
      years of age, from the Atherosclerosis Risk in Communities (ARIC) study cohort.
      Trait anger was assessed using the 10-item Spielberger Trait Anger Scale.
      Arterial stiffness was assessed by pulsatile arterial diameter change (PADC)
      derived from echo-tracking ultrasound methods; the smaller the PADC, the stiffer
      the common carotid artery. In men, trait anger was significantly associated with
      PADC, independent of the established cardiovascular disease risk factors
      (p=0.04). PADC decreased from the first (lowest anger group) to the second
      quintile of anger, but there was no progressive decrease thereafter. Also
      observed was a 13-microm (95% confidence interval [CI], 1-25) difference in the
      magnitude of PADC from the lowest to the uppermost quintile of anger (PADC
      [standard error], 421 [4] microm vs. 408 [5] microm). In women, the association
      was marginally significant (p=0.07). The low-high difference in the magnitude of
      PADC (PADC [standard error], 397 [3] microm vs. 406 [4] microm) was inverse (-9
      microm 95% CI, -19 to 2). Conclusions indicate that very high trait anger is
      associated with arterial stiffness in men.

PMID- 16407699
TI  - Angiotensin-converting enzyme genotype and adherence to aerobic exercise
      training.
AB  - Angiotensin-converting enzyme (ACE) has two common genetic variants: the
      insertion (I) and deletion (D) forms. ACE levels are greater in subjects with the
      D allele, and several studies suggest superior endurance performance in subjects
      with the I allele. The authors recently reported the results of a 6-month
      exercise training protocol examining the effect of apolipoprotein E on the lipid
      response. The present report examines the relationship of ACE genotype and
      exercise adherence. DNA samples were available for 110 subjects: 14 I/I, 52 I/D,
      and 44 D/D. Baseline and change in maximal oxygen uptake, body mass index,
      skinfold thickness, and serum lipids did not differ by ACE genotype, but
      adherence to exercise training was higher in I carriers than in D homozygotes.
      These preliminary results suggest that ACE genotype affects exercise adherence
      and raises the possibility that superior endurance capacity in subjects with the
      I allele is related to a genetic propensity to adhere to an exercise regimen.

PMID- 16407700
TI  - Conventional, emerging, heredity, lifestyle, and psychosocial coronary risk
      factors: relationships to subclinical atherosclerosis.
AB  - The authors examined the relationship between calcified coronary atherosclerosis
      and an array of cardiovascular risk factors in sequential logistic models to
      determine the extent to which these markers overlap in their identification of
      patients at risk for developing coronary heart disease. The prevalence of
      coronary artery calcium using electron beam computed tomography was 19.4% in this
      cross-sectional study of a prospective, consecutive, screening cohort of 1999
      healthy United States Army personnel (aged 39-50 years). The proportion of the
      total variance of coronary artery calcium explained by sequential logistic models
      incorporating conventional, emerging, hereditary, lifestyle, and psychosocial
      cardiovascular risk variables increased progressively from 9.7% to 14.5%. The
      best-fit logistic model for the prediction of coronary artery calcium identified
      age, male gender, Framingham risk score, total cholesterol, high-density
      lipoprotein cholesterol, triglycerides, smoking, a family history of coronary
      heart disease, white race, physical inactivity, and lower depression scores as
      significant independent correlates of coronary artery calcium. These data
      indicate that the explanatory power of models for atherosclerosis can be
      significantly improved with the use of emerging, heredity, lifestyle, and
      psychosocial factors. The large residual variance, however, supports the
      potential of atherosclerosis imaging to incrementally and independently identify
      coronary heart disease risk.

PMID- 16407701
TI  - Optimal vascular protection: a case for combination antihypertensive therapy.
AB  - Endothelial dysfunction is an important factor in the pathogenesis of
      atherosclerosis, hypertension, and heart failure. The endothelium mediates
      vascular tone, structure, and function by the release and regulation of multiple
      vasoactive substances that promote or inhibit vasodilation, vasoconstriction,
      cell growth, and other mechanisms. The effect of antihypertensive drugs on
      endothelial function may be an important indicator of their ability to reduce
      risks for cardiovascular morbidity and mortality. Endothelium-dependent
      vasodilation induced by various antihypertensive drugs is accurately measured
      with high-resolution ultrasound of flow-mediated dilation of the brachial artery.
      Calcium channel blockers and angiotensin-converting enzyme inhibitors have been
      shown to reverse endothelial dysfunction. The benefits of angiotensin-converting
      enzyme inhibitors and calcium channel blockers on the endothelium are believed to
      derive from their effects on nitric oxide production and antioxidant effects,
      possibly independent of blood pressure reduction. Due to their complementary
      mechanisms of action, it has been hypothesized that the combination of an
      angiotensin-converting enzyme inhibitor and a calcium channel blocker will
      provide superior cardiovascular protection, in part by producing an additive
      effect of increased nitric oxide availability, when compared with either agent
      alone.

PMID- 16407702
TI  - Intracardiac devices for stroke prevention.
AB  - Stroke is a significant cause of serious disability and death worldwide. A
      substantial proportion of strokes are related to an underlying cardiac embolic
      source, most commonly in association with atrial arrhythmias
      (fibrillation/flutter). Atrial fibrillation is considered a major risk factor for
      stroke. Although long-term prophylactic oral anticoagulation has been shown to be
      very effective in reducing stroke in patients with atrial fibrillation, it has a
      number of major limitations and is not feasible in all patients. In such cases,
      the use of percutaneously (transvenous) implanted left atrial appendage occlusive
      devices or surgical appendage obliteration is being explored. Similarly, the
      presence of a patent foramen ovale, especially in the presence of an atrial
      septal aneurysm, is now recognized as an important potential mediator of
      paradoxical cardiogenic embolism. Percutaneous patent foramen ovale closure is
      becoming increasingly established as a safe and effective means of preventing
      recurrent strokes in the presence of a patent foramen ovale. In this account, the
      authors discuss the intracardiac devices and techniques available and the
      relative merits of their use for stroke prevention.

PMID- 16407704
TI  - Walking: the undervalued prescription.

PMID- 16407703
TI  - Implantable cardioverter-defibrillators: a new preventive medical option.
AB  - Implantable cardioverter-defibrillator (ICD or defibrillator) therapy has
      revolutionized the fields of cardiology and electrophysiology. Hundreds of
      thousands of patients at risk for sudden cardiac death receive them each year.
      The devices are not much larger than a pacemaker, and they have full pacemaker
      capabilities in addition to being able to shock patients out of life-threatening
      ventricular arrhythmias. The Multicenter Automatic Defibrillator Implantation
      Trial (MADIT) in 1996 was a landmark trial that showed for the first time a
      mortality benefit of ICD therapy over medications in patients at high risk for
      sudden death. Multicenter Automatic Defibrillator Implantation Trial II,
      published in 2002, extended these results to all patients with ischemic heart
      failure with depressed heart function. Candidates for ICD implantation include
      most patients with an ejection fraction of <30%, especially those with coronary
      artery disease. More work needs to be done to define those patients with
      nonischemic cardiomyopathies who will benefit from ICDs and biventricular pacing
      for heart failure.

PMID- 16407705
TI  - ASCOT-Blood Pressure Trial (ASCOT-BPLA) and HOPE-TOO.

PMID- 16407706
TI  - "Flush-free niacin": dietary supplement may be "benefit-free".
AB  - This report describes a patient with coronary artery disease who was instructed
      to take extended-release niacin to treat low high-density lipoprotein cholesterol
      and instead purchased "flush-free niacin" available at the pharmacy. There was no
      significant change in his lipids. Once the patient switched to extended-release
      niacin, the anticipated beneficial effects were seen. The article reviews the
      composition of flush-free niacin, its purported and real lipid effects, and warns
      against the effects of misleading marketing.

PMID- 16407707
TI  - The IDEAL Trial: less is more.

PMID- 16407709
TI  - Dairy products and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Although it has often been postulated that the consumption of
      dairy products is associated with a high risk of coronary heart disease, study
      results have been conflicting. This review summarizes recent observational and
      human intervention trial findings on dairy products and cardiovascular disease.
      RECENT FINDINGS: Results from more recent observational studies on dairy products
      and milk disagree. This may be because of the very different methods used
      combined with several methodological problems. A somewhat surprising beneficial
      association between the intake of dairy products and the metabolic syndrome was
      observed in some studies, although not in a single study of elderly women. Milk
      may have the same cholesterol-raising properties as butter, whereas cheese does
      not seem to increase plasma cholesterol. Some milk products fermented by specific
      bacterial strains have been shown to have rather moderate cholesterol-reducing
      properties. There is also good evidence that certain fermented products
      (especially by Lactobacillus helveticus) have a mildly decreasing effect on
      hypertension, probably because of bioactive peptides. SUMMARY: When guiding
      principles such as balance, variety and moderation are stressed, there is no
      strong evidence that dairy products increase the risk of coronary heart disease
      in healthy men of all ages or young and middle-aged healthy women. Human studies
      should investigate the role of dairy products with respect to sex and age by
      including classic and novel risk markers of coronary heart disease. Specific
      fermented milks may be beneficial in the future prevention of hypertension. The
      beneficially neutral effect of cheese on coronary heart disease risk factors
      should be elucidated further.

PMID- 16407710
TI  - Carotenoids and cardiovascular disease: what research gaps remain?
AB  - PURPOSE OF REVIEW: Dietary and blood carotenoids, including alpha-carotene, beta
      carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin, have been examined
      in a number of epidemiological studies in recent years for the risk of
      cardiovascular disease. This review assimilated the existing and recent
      literature on carotenoids and cardiovascular disease and considered what research
      gaps may remain. RECENT FINDINGS: Numerous large cohort studies have been
      published in largely American men and women that have examined dietary intake or
      blood levels of total or individual carotenoids with the risk of various
      cardiovascular endpoints. Overall, early, promising results have grown
      increasingly inconsistent over time. More recently, studies examining lycopene
      and lutein/zeaxanthin have offered more promising data on a possible, but not yet
      established, inverse association with the risk of cardiovascular disease. Recent
      epidemiological data on beta-cryptoxanthin and cardiovascular disease are
      lacking. Primary and secondary prevention trials have extensively examined beta
      carotene, but not other carotenoids, for the risk of cardiovascular disease as
      either the primary or secondary endpoint with largely null results. More recent
      studies have focused on individual carotenoids in relation to cardiovascular
      disease and require a more careful evaluation of potential mechanisms of effect.
      SUMMARY: The promise of early epidemiological studies on carotenoids and
      cardiovascular disease paved the way to largely disappointing results from
      several large prevention trials of beta-carotene. Emerging recent evidence of
      potential cardioprotective effects for lycopene and other carotenoids besides
      beta-carotene in the diet and blood suggest that there is more to be learned in
      the story of carotenoids and both atherosclerotic progression and clinically
      manifested cardiovascular disease.

PMID- 16407711
TI  - Factors influencing the relation between alcohol and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Light-to-moderate alcohol intake is known to have
      cardioprotective properties in some subsets of the population. This review
      focuses on factors that modify the relation between alcohol and cardiovascular
      disease. RECENT FINDINGS: Several large American studies have shown that the J
      shaped relation is influenced by age and coronary heart disease risk-factor
      status since only middle-aged and elderly and those already at risk of developing
      coronary heart disease seem protected by drinking alcohol. It has also been
      suggested that only those who have a steady - in contrast to a binge - intake of
      alcohol have benefits with regard to cardiovascular disease. Prospective studies
      from the UK, Sweden and Denmark have further suggested that wine drinkers have a
      lower mortality than beer and spirits drinkers. SUMMARY: The J-shaped relation
      between alcohol intake and cardiovascular disease seems to be influenced by age,
      gender, drinking pattern and type of alcohol.

PMID- 16407712
TI  - The use of fatty acid biomarkers to reflect dietary intake.
AB  - PURPOSE OF REVIEW: This review compares fatty acid biomarkers to assess
      compliance in dietary intervention trials with their application in
      epidemiological studies. RECENT FINDINGS: Although many studies have used fatty
      acid biomarkers to assess compliance in short-term dietary intervention trials
      and habitual diets in observational studies, there is little information on the
      reliability and comparability of these measures. In this review, we summarize the
      usefulness and limitations of fatty acid biomarkers in clinical and
      epidemiological studies. As there are very few recent publications in this area,
      a complete literature review is provided. SUMMARY: Several options are available
      for the biological assessment of dietary fatty acids. The type of study (short or
      long-term), the metabolic characteristics and expected variability in the fatty
      acids of interest are major considerations when determining which tissues reflect
      a better measure of true intake. Certain fatty acids may not be suitable to
      assess differences in intake under non-isocaloric conditions and when trying to
      identify small differences. Serum cholesterol ester is the most suitable serum
      fraction to assess short-term dietary compliance, but given the multiple factors
      that affect response, the quantification of compliance should be interpreted with
      caution. Adipose tissue is the biomarker of choice for long-term intake, but a
      preferred blood constituent (plasma versus erythrocytes) is difficult to
      establish given the data available to date. Future studies should explore the use
      of whole blood as an alternative choice to measure fatty acid intake in
      epidemiological studies.

PMID- 16407713
TI  - Recent studies of lipoprotein kinetics in the metabolic syndrome and related
      disorders.
AB  - PURPOSE OF REVIEW: Dyslipoproteinemia is a cardinal feature of the metabolic
      syndrome that accelerates atherosclerosis. Recent in-vivo kinetic studies of
      dyslipidemia in the metabolic syndrome are reviewed here. RECENT FINDINGS: The
      dysregulation of lipoprotein metabolism may be caused by a combination of
      overproduction of VLDL apolipoprotein B-100, decreased catabolism of
      apolipoprotein B-containing particles, and increased catabolism of HDL
      apolipoprotein A-I particles. Nutritional modifications and increased physical
      exercise may favourably alter lipoprotein transport by collectively decreasing
      the hepatic secretion of VLDL apolipoprotein B and the catabolism of HDL
      apolipoprotein A-I, as well as by increasing the clearance of LDL apolipoprotein
      B. Conventional and new pharmacological treatments, such as statins, fibrates and
      cholesteryl ester transfer protein inhibitors, can also correct dyslipidemia by
      several mechanisms, including decreased secretion and increased catabolism of
      apolipoprotein B, as well as increased secretion and decreased catabolism of
      apolipoprotein A-I. SUMMARY: Kinetic studies provide a mechanistic insight into
      the dysregulation and therapy of lipid and lipoprotein disorders. Future research
      mandates the development of new tracer methodologies with practicable in-vivo
      protocols for investigating fatty acid turnover, macrophage reverse cholesterol
      transport, cholesterol transport in plasma, corporeal cholesterol balance, and
      the turnover of several subpopulations of HDL particles.

PMID- 16407714
TI  - Lifestyle intervention to prevent diabetes: intensive and cost effective.
AB  - PURPOSE OF REVIEW: Type 2 diabetes is a major cause of morbidity and mortality,
      and despite treatment advances appears to be increasing in incidence. Since
      individuals at risk for the disease are usually identifiable in the prediabetic
      phase of impaired glucose tolerance, early intervention might prevent diabetes
      and hence its complications from developing. Obesity and sedentary living are
      powerful determinants of diabetes, and thus lifestyle change is a logical
      approach to prevention of this disease. Recent clinical trials have now tested
      the effectiveness of this intervention and form the basis for this review. RECENT
      FINDINGS: Three clinical trials have demonstrated that, compared with usual care,
      lifestyle intervention significantly reduced progression rates to diabetes in
      prediabetic individuals. Each trial incorporated individualization and repeated
      long-term contacts with facilitators, in which dietary and physical activity goal
      setting and behavior modification were central themes. Progression to diabetes
      was reduced in the Da Qing study by approximately 40%, in the Finnish Diabetes
      Prevention Study by 58% and in the Diabetes Prevention Program by 58%. The
      Diabetes Prevention Program included a cost-benefit unit that estimated the per
      capita costs of the lifestyle intervention to exceed that of the usual care group
      by Dollars 3540, which translated to a cost of Dollars 15,700 per case of
      diabetes prevented. Lifetime cost-utility analysis demonstrated an overall cost
      of Dollars 1100 per quality-adjusted life year. SUMMARY: These findings make the
      case for translation of research findings to healthcare systems. Although there
      is more to be learned about effective strategies in clinical practice, it seems
      clear that the intervention needs to incorporate individualization and long-term
      interaction with trained facilitators.

PMID- 16407715
TI  - Circulating biomarkers of extracellular matrix remodeling and risk of
      atherosclerotic events.
AB  - PURPOSE OF REVIEW: Disturbances of the synthesis and breakdown of the
      extracellular matrix of arterial walls have emerged as key features of the
      atherosclerotic process. Altered levels of circulating extracellular matrix
      markers have frequently been observed in relation to manifestations of
      atherosclerotic disease and its risk factors. RECENT FINDINGS: Research has been
      focused on the matrix-degrading metalloproteinases, their tissue inhibitors, and
      procollagen peptides. The most promising matrix metalloproteinase is matrix
      metalloproteinase-9, which has been observed to predict rapid coronary artery
      narrowing, ischemic heart disease incidence, abdominal aortic aneurysm expansion,
      worse outcome in stroke patients, and cardiovascular death. The use of tissue
      inhibitors of metalloproteinases for prognostication is uncertain thus far. The
      procollagen marker with most prognostic potential is the marker for type III
      collagen turnover rate, the N-terminal propeptide PIIINP, higher levels of which
      predict an adverse outcome after a myocardial infarction and in chronic heart
      failure, and portend abdominal aortic aneurysm expansion and risk of rupture.
      Also, the marker for type I collagen synthesis, the C-terminal propeptide PICP,
      predicts adverse outcomes following myocardial infarction and in chronic heart
      failure. Extracellular matrix remodeling is also a promising therapeutic target,
      being favorably affected by several conventional cardiovascular drugs and select
      dietary interventions. Synthetic matrix metalloproteinase inhibitors are also
      under development. SUMMARY: Circulating matrix markers have emerged as candidate
      biomarkers for predicting risk of subsequent atherosclerotic events. Future large
      longitudinal observational and intervention studies will determine the role of
      matrix biomarkers in diagnosis and prognostication, and as targets for
      intervention in cardiovascular diseases.

PMID- 16407717
TI  - Bibliography. Current world literature. Nutrition and metabolism.

PMID- 16407716
TI  - Treating dyslipidemia in the elderly.
AB  - PURPOSE OF REVIEW: The treatment of dyslipidemia has been dynamic over the past
      several years. Of special importance is the impact of recent clinical trial data
      on management strategies of dyslipidemia in the elderly. People 65 years and
      older are living longer and are the fastest growing subset of the US population,
      necessitating more attention to chronic disease conditions that manifest in this
      age group. This review addresses guidelines of lipid management, discusses data
      that support their use, and examines the benefits of lipid-lowering therapy in
      the elderly with attention to the chronic conditions that are common in this
      population. RECENT FINDINGS: Clinical trials completed since the publication of
      the 2001 National Cholesterol Education Program (NCEP) Adult Treatment Panel III
      guidelines support the use of lipid-lowering therapy in the elderly population.
      Lipid-lowering therapy has not only proven to be generally safe in the elderly,
      but has also proven effective in helping manage the chronic disease conditions
      that are common in this age group. SUMMARY: The elderly segment of our population
      continues to grow. Along with this growth in population is a growth in incidence
      of cardiovascular disease, the metabolic syndrome, chronic kidney disease,
      cerebrovascular disease, and diabetes mellitus. There is no known panacea for
      managing these chronic disease conditions; however, lipid-lowering therapy has
      been shown to prevent or delay the progression of these diseases and the
      mortality and morbidity that accompanies them.

PMID- 16407718
TI  - Nutrition and metabolism: race, sex and the metabolic syndrome.

PMID- 16407720
TI  - Lipids metabolism: lipids and lipoproteins - effect on blood clotting and risk of
      venous thrombosis.

PMID- 16407719
TI  - Genetics and molecular biology: macrophage ACAT depletion - mechanisms of
      atherogenesis.

PMID- 16407721
TI  - Hyperlipidaemia and cardiovascular disease: oxidative damage and atherosclerosis.

PMID- 16407722
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 16407723
TI  - Therapy and clinical trials: plant sterols and stanols in management of
      hypercholesterolemia: where are we now?

PMID- 16407728
TI  - Current perspectives in nutrition and cardiovascular disease.

PMID- 16407729
TI  - Fiber and cardiovascular disease risk: how strong is the evidence?
AB  - Dietary fiber consists of edible parts of plants or analogous carbohydrates that
      are resistant to digestion and absorption in the human small intestine. Fiber can
      be classified as a dietary source (eg, cereal, fruit, vegetable, or legume) or as
      a supplement. Based on chemical properties, fiber can be divided to water-soluble
      (eg, beta-glucans, pectin, and guar) and insoluble (eg, cellulose and lignin)
      forms. An increasing number of observational findings have reported a lower
      incidence of coronary heart disease in subjects who report consuming diets high
      in fiber. Dietary fiber is thought to affect several cardiovascular disease (CVD)
      risk factors. Soluble fiber decreases serum total and low-density lipoprotein
      cholesterol concentrations and improves insulin resistance. The effect of fiber
      on inflammatory markers and coagulation is not yet well established. While
      soluble, gel-forming fiber has beneficially affected CVD risk factors, food
      sources of mainly insoluble fibers, primarily contributed by cereal products,
      have been the most consistently associated with lower incidence rates of CVD.
      Despite this contradiction, the evidence promotes a food-based approach favoring
      increased intake of whole-grain cereals, fruit, and vegetables providing a
      mixture of different types of fibers for CVD prevention.

PMID- 16407732
TI  - Omega-3 fatty acids: role in cardiovascular health and disease.
AB  - Dietary omega-3 polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic
      acids, play an important role in cardiovascular health and disease. Clinical
      trials provide substantial evidence to support current dietary recommendations
      for omega-3 fatty acids in cardiovascular disease management. The
      cardioprotective benefits of omega-3 fatty acids may be attributed to multiple
      physiological effects on lipids, blood pressure, vascular function, cardiac
      rhythms, platelet function, and inflammatory responses. The metabolism of omega-3
      fatty acids, physiological effects, and clinical considerations with current
      dietary recommendations and sources of omega-3 fatty acids are presented.

PMID- 16407734
TI  - Overweight and obesity in the context of heart failure: implications for practice
      and future research.
AB  - Heart failure (HF) is a major cardiovascular disorder, public health concern, and
      growing epidemic that affects approximately 5,000,000 people in the United States
      with 550,000 new cases reported annually. The clinical and economic impact of HF
      is associated with high hospitalization and early readmission rates. Recognizing
      factors that contribute to increasing the risk for HF, particularly the
      persistent rise in prevalence of overweight and obesity, may be imperative to
      reducing the burdens of this poorly prognostic disease process. Overweight and
      obesity have been associated with increased morbidity and mortality, and have
      incited extensive interest in therapeutic interventions. However, within the last
      decade, studies have illustrated the positive effects of overweight and obesity
      on survival after the onset of HF, which has prompted a variance of opinion
      within the healthcare community. This article reviews data supporting both the
      negative and positive effects of overweight and obesity in relationship to HF
      with implications for future research, and describes recommendations for practice
      as it relates to lifestyle modification through diet, exercise, and cognitive
      behavioral therapy.

PMID- 16407731
TI  - Supplemental conditionally essential nutrients in cardiovascular disease therapy.
AB  - Conditionally essential nutrients (CENs) are organic compounds that are
      ordinarily produced by the body in amounts sufficient to meet its physiological
      requirements. However, in disorders, such as cardiovascular disease (CVD), and in
      other physiologically stressful conditions, their biosynthesis may be inadequate.
      Under these circumstances, CENs become essential nutrients, comparable to
      vitamins. The CENs of primary importance in CVD, based on the quantity and
      quality of human clinical studies, are l-arginine, l-carnitine, propionyl-l
      carnitine, and coenzyme Q10. Controlled studies of these CENs are reviewed in
      depth. Taurine is a CEN of secondary importance caused by a limited human
      database. Other putative CENs include alpha-lipoic acid, betaine, chondroitin
      sulfate, glutamine, and d-ribose, each of which is mentioned in passing.
      Collectively, CENs have demonstrated favorable clinical effects in CVDs,
      including chronic heart failure, myocardial infarction, angina pectoris, and in
      CVD risk factors, such as hypertension, hyperlipidemia, and lipoprotein(a).
      Limited research has pointed to possible benefits in CVD therapy accruing from
      supplementation with several CENs in combination. Additional controlled clinical
      studies of CENs in CVD are urgently needed. In view of the efficacy and safety of
      appropriate supplementation with CENs, it is strongly suggested that healthcare
      professionals become knowledgeable of these potentially important additions to
      the CVD therapeutic armamentarium.

PMID- 16407735
TI  - Popular weight reduction diets.
AB  - The percentage of people who are overweight and obese has increased tremendously
      over the last 30 years. It has become a worldwide epidemic. This is evident by
      the number of children are being diagnosed with a body mass index >85th
      percentile, and the number of children begin diagnosed with type 2 diabetes
      mellitus, a disease previously reserved for adults. The weight loss industry has
      also gained from this epidemic; it is a billion dollar industry. People pay large
      sums of money on diet pills, remedies, and books, with the hope of losing weight
      permanently. Despite these efforts, the number of individuals who are overweight
      or obese continues to increase. Obesity is a complex, multifactorial disorder. It
      would be impossible to address all aspects of diet, exercise, and weight loss in
      this review. Therefore, this article will review popular weight loss diets, with
      particular attention given to comparing low fat diets with low carbohydrate
      diets. In addition, the role that the environment plays on both diet and exercise
      and how they impact obesity will be addressed. Finally, the National Weight
      Control Registry will be discussed.

PMID- 16407736
TI  - Total homocysteine concentration and associated cardiovascular and renal
      implications in adults.
AB  - Hyperhomocysteinemia has been linked to an increased risk for cardiovascular (CV)
      disease since 1969. Recent epidemiological and cohort observations continue to
      confirm this relationship, provided the homocysteine concentration is elevated.
      This elevation in homocysteine concentration and increased CV disease risk are
      particularly strong in patients with renal disease. Hyperhomocysteinemia is also
      related to declining status of vitamins B6 and B12, folate, and in some cases
      riboflavin. This relationship between vitamins and homocysteine concentration has
      provided the basis for clinical trials targeting CV risk reduction by vitamin
      supplementation. This review describes the evidence behind vitamin
      supplementation as it pertains to homocysteine status and make recommendations
      for vitamin intake management in patients with hyperhomocysteinemia, including
      those patients with renal disease.

PMID- 16407738
TI  - Nutrition in chronic heart failure with coexisting chronic kidney disease.
AB  - BACKGROUND AND RESEARCH OBJECTIVES: Patients with heart failure (HF) may be
      predisposed to malnutrition. Little is known about the nutritional status of
      patients with HF, particularly patients who have coexisting major medical
      conditions such as chronic kidney disease. The purposes of this study were to (1)
      describe the nutritional status of 211 patients with chronic HF, (2) examine
      relationships between nutrition variables and health-related quality of life, and
      (3) evaluate the nutritional status of the subset of HF patients with coexisting
      chronic kidney disease. SUBJECTS AND METHODS: The sample included 211 patients
      with chronic HF recruited for a larger study about health-related quality of
      life. Clinical data were retrieved retrospectively from the computerized medical
      records system at the study site. RESULTS AND CONCLUSIONS: Mean body mass index
      of the 122 patients for which height was available was 31.4, and no differences
      in body mass index were noted among patients with varying New York Heart
      Association class functional status. Evaluation of the mean laboratory values
      indicated that patients had abnormal elevations of serum glucose, hemoglobin A1C,
      creatinine, and low-density lipoprotein cholesterol. Higher hemoglobin A1C levels
      were significantly correlated with poorer health-related quality-of-life scores,
      although the magnitude of the correlations was modest. Estimated glomerular
      filtration rate indicated that 54 (27%) of the HF patients likely had coexisting
      chronic kidney disease, and these patients had significantly lower serum albumin
      and worsening anemia. The results indicate the need for future prospective
      studies that incorporate evaluation of nutritional status and the ways in which
      coexisting chronic kidney disease influences outcomes.

PMID- 16407739
TI  - A review of methods to measure dietary sodium intake.
AB  - With the rising prevalence of heart failure, it is imperative to investigate
      reasons for dietary sodium nonadherence and to develop evidence-based
      interventions to promote adherence. However, one of the biggest obstacles in
      studying adherence to a low sodium diet is the imprecision in measurement of
      dietary sodium intake. The purpose of this article is to critically review
      current methods used to measure dietary sodium intake. Specifically, 24-hour
      urine, single- and multiple-day food records, and 24-hour dietary recalls are
      compared and contrasted. The reliability and validity of these methods are
      discussed. When choosing a method to measure dietary sodium, it is important also
      to consider other strengths and weaknesses of each method. The "best" method to
      be used in research may depend not only on the above information, but also on the
      research question as well as characteristics of the population under study.

PMID- 16407737
TI  - Total homocysteine, diet, and lipid profiles in type 1 and type 2 diabetic and
      nondiabetic adolescents.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Limited research is available on the possible
      differences in the cardiovascular risk factors of total homocysteine (tHcy),
      dietary energy, and lipids among adolescents with type 1 diabetes mellitus (DM),
      type 2 DM, or healthy controls. This study's primary aim was to compare the
      dietary energy and the intake of macronutrients and micronutrients of folate, and
      vitamins B6 and B12, as well as lipids and tHcy for adolescents with type 1 DM,
      type 2 DM, and healthy non-DM controls. SUBJECTS AND METHODS: This secondary
      analysis of the merging of 2 datasets included the following adolescents: 50 with
      type 1 DM, 14 with type 2 DM, and 53 controls. Mean ages for those with type 1
      versus type 2 DM were 15.2 +/- 1.9 versus 16.1 +/- 1.9 years, respectively. Mean
      age for the controls was 16.5 +/- 1.0 years. Variables included fasting tHcy and
      lipids, and 24-hour dietary recalls for macronutrients and micronutrients.
      Hemoglobin A1c was obtained for those with DM. Statistical analyses included one
      way analyses of variance, Pearson correlations, and stepwise regression. RESULTS
      AND CONCLUSIONS: Adolescents with type 1 DM had the lowest tHcy values (P <.05),
      which were reflective of the limited extant research with this population. Lipid
      profiles and dietary energy did not differ significantly among the 3 groups.
      Hemoglobin A1c was related to total cholesterol and triglycerides in those with
      type 1 DM, confirming the importance of promoting better metabolic control in
      lipid management for these youth. Future research should continue to explore the
      validity of tHcy and lipids as predictors of CV risks for youth with type 1 and
      type 2 DM.

PMID- 16407740
TI  - News from the field of women's heart health.

PMID- 16407754
TI  - Evaluation of cerebral dyschromatopsia using color afterimage.
AB  - Cerebral dyschromatopsia is traditionally evaluated by color discrimination tests
      such as the Farnsworth-Maunsell 100 Hue Test. These tests are also used to
      evaluate color-perception deficits caused by eye disease, and they do not tell us
      whether color perception is impaired in the eye or in the brain. Here, we used
      color afterimage to isolate color-perception deficits in the brain from those in
      the eyes, in a patient with cerebral dyschromatopsia. The results showed that the
      patient perceived color afterimage of yellow and blue with abnormal duration and
      chromaticity. On the other hand, the patient performed normally on the Farnsworth
      Maunsell 100 Hue Test. We conclude that the color afterimage test would be useful
      to evaluate color perception in the brain.

PMID- 16407755
TI  - Role of Src family kinase in the rewarding effect and hyperlocomotion induced by
      morphine.
AB  - The aim of the present study was to investigate the effect of a selective Src
      family kinase inhibitor, 4-amino-5-(4-chlorophenyl)-(t-butyl)pyrazolo[3,4
      D]pyrimidine (PP2), on the rewarding effect and hyperlocomotion induced by
      morphine. An intracerebroventricular pretreatment with PP2 (0.1-10 nmol/mouse)
      significantly suppressed the morphine-induced rewarding effect and
      hyperlocomotion in a dose-dependent manner. We also investigated the changes in
      immunoreactivities to phosphorylated-Src family kinase in the nucleus accumbens
      of mice showing the morphine-induced rewarding effect. We found for the first
      time that Src family kinase is activated in the nucleus accumbens of mice showing
      the morphine-induced rewarding effect as compared with that found in saline
      treated control mice. These findings suggest that Src family kinases in the
      nucleus accumbens are involved in the rewarding effect and hyperlocomotion
      induced by morphine.

PMID- 16407756
TI  - Sonic hedgehog promotes mouse inner ear progenitor cell proliferation and hair
      cell generation in vitro.
AB  - Sonic hedgehog (Shh) signaling is essential for auditory cell fate determination
      and inner ear dorsal/ventral patterning during development. Here, we show that
      Shh accelerates inner ear progenitor cell proliferation, and the inhibitor of Shh
      signaling cyclopamine reduces mitotic growth of otocyst cells in vitro. The
      number of hair cells in cultures of inner ear progenitor cells that were treated
      with Shh was significantly higher than that in control cultures. When Shh
      signaling was blocked with cyclopamine, hair cell generation was largely
      inhibited. Our results suggest that Shh may be a regulator of inner ear
      progenitor cell growth and hair cell generation.

PMID- 16407757
TI  - Fewer PrPc myeloid-based cells in sheep with the prion-resistant genotype.
AB  - Numerous sheep with the prion gene (PRNP) that encodes for 171QQ develop scrapie,
      a neurodegenerative prion disease of sheep. Relatively few cases of scrapie
      affected sheep with PRNP genetics that encode for 171RR, however, have been
      found. Using flow cytometric analysis, statistically fewer PrPc-positive
      microglia and monocytes were observed from sheep with 171RR PRNP genetics than
      from sheep with 171QQ PRNP genetics (P<0.05). One possibility for the lack of
      PrP(Sc) accumulation in brains and lymph nodes of scrapie-exposed sheep with
      171RR PRNP genetics is because of fewer PrPc-positive myeloid-derived cells
      available for conversion of PrPc to PrP(Sc).

PMID- 16407758
TI  - Spatial profile of back-propagating action potential-evoked Ca2+ transients in
      basal dendrites.
AB  - Calcium influx in basal dendrites evoked by back-propagating action potentials is
      important for understanding the input-specific modulation of synaptic
      transmission. Calcium transients evoked by back-propagating action potentials
      were measured for the basal dendrites of layer II/III pyramidal neurons in visual
      cortex slices. In contrast to apical dendrites, the peak calcium transients
      evoked by a single somatic action potential increased with distance from the
      soma. The peak calcium transients evoked by bursts of back-propagating action
      potentials (three or five pulses, 20 Hz) were greater than those evoked by a
      single back-propagating action potential. These different spatial profiles for
      calcium transients triggered by back-propagating action potentials between apical
      and basal dendrites suggest that the segregated inputs from brain areas might be
      modulated in different ways, according to their synaptic location.

PMID- 16407760
TI  - Dissociable modulating effect of repetitive transcranial magnetic stimulation on
      sensory and pain perception.
AB  - The effects of high frequency repetitive transcranial magnetic stimulation on
      sensory perception and the pain tolerance thresholds were investigated applying
      both motor cortex stimulation and medial frontal cortex stimulation in normal
      study participants. Both the sensory perception and pain tolerance thresholds
      were significantly increased in the motor cortex stimulation, whereas the pain
      tolerance thresholds, but not the sensory perception was significantly decreased
      in the medial frontal cortex stimulation. These results suggest the dissociable
      modulating effects of sensory and pain perception by the high frequency
      repetitive transcranial magnetic stimulation on the medial pain regulating
      system, but not the lateral pain regulating system.

PMID- 16407759
TI  - Functional expression of transient receptor potential vanilloid 4 in the mouse
      cochlea.
AB  - Transient receptor potential vanilloid 4, the Ca2+-permeable cation channel has
      been proposed as an osmosensitive and a mechanosensitive channel. We investigated
      functional expression of transient receptor potential vanilloid 4 in inner hair
      cells, outer hair cells, and spiral ganglion neurons of the mouse cochlea.
      Transient receptor potential vanilloid 4 mRNA and protein were expressed in inner
      hair cells, outer hair cells, and spiral ganglion neurons on the basis of the
      findings of reverse transcriptase-polymerase chain reaction, single-cell reverse
      transcriptase-polymerase chain reaction, and immunohistochemistry, whereas they
      were negative in transient receptor potential vanilloid 4-/- mice cochleae.
      Hypotonic stimulation and 4-alpha-phorbol 12,13-didecanoate, a transient receptor
      potential vanilloid 4 synthetic activator, increased the intracellular Ca2+
      concentrations in wild-type outer hair cells, whereas in transient receptor
      potential vanilloid 4-/- mice, outer hair cells failed to exhibit a Ca2+ response
      to both stimulations. In conclusion, transient receptor potential vanilloid 4 may
      function as an osmosensory and a mechanosensory receptor in the cochlea.

PMID- 16407761
TI  - Involvement of transient receptor potential vanilloid-1 in calcium current
      inhibition by capsaicin.
AB  - Capsaicin has been used as a topical analgesic to treat diverse pain conditions.
      We investigated the molecular mechanisms that mediate the inhibition of high
      voltage-activated calcium channel currents (ICa) using trigeminal ganglion
      neurons and a heterologous expression system. Capsaicin inhibited ICa in
      capsaicin-sensitive trigeminal ganglion neurons, but not in capsaicin-insensitive
      neurons. Single-cell reverse-transcription polymerase chain reaction revealed the
      expression of TRPV1 only in capsaicin-sensitive neurons. Capsaicin inhibited ICa
      in transient receptor potential vanilloid-1-expressing C2D7 cells stably
      expressing human N-type calcium channels, whereas capsaicin failed to inhibit ICa
      in naive C2D7 cells with no endogenous transient receptor potential vanilloid-1
      expression. Calcium influx via transient receptor potential vanilloid-1 is not
      likely to play a critical role in capsaicin-induced ICa inhibition in trigeminal
      ganglion neurons. ICa inhibition might be one of the mechanisms for the analgesic
      effect of capsaicin.

PMID- 16407762
TI  - Visual distraction: a behavioral and event-related brain potential study in
      humans.
AB  - Recent studies reported that the detection of changes in the visual stimulation
      results in distraction of cognitive processing. From event-related brain
      potentials it was argued that distraction is triggered by the automatic detection
      of deviants. We tested whether distraction effects are confined to the detection
      of a deviation or can be triggered by changes per se, namely by rare stimuli that
      were not deviant with respect to the stimulation. The results obtained comparable
      early event-related brain potential effects for rare and deviant stimuli,
      suggesting an automatic detection of these changes. In contrast, behavioral
      distraction and attention-related event-related brain potential components were
      confined to deviant stimuli. This finding suggests that deviancy from a given
      standard adds a genuine contribution to distraction.

PMID- 16407763
TI  - Effect of connectivity and bistability on the visual potentials evoked by
      illusory figures.
AB  - The present study aimed at testing functional hypotheses regarding two brain
      potentials elicited by illusory figures. Accordingly, the N1 potential indexes
      mechanisms connecting the separate parts of the illusory form, whereas a
      subsequent negative potential indexes compensatory processes triggered by
      perceptual difficulty. Here, perceptual difficulty was induced by bistability;
      that is, by equating the probability of perceiving the illusory form to that of
      perceiving the independent separate parts. We compared the brain potentials
      evoked by a strongly connected illusory square, with almost no bistability, with
      those evoked by a weakly connected illusory square presenting strong bistability.
      Consistent with our hypotheses, the latter figure evoked the smallest N1 and a
      larger negative component peaking at 360 ms (N360). These results strengthen the
      link between N1 and connection and between negativity to perceptual difficulty
      and perceptual difficulty.

PMID- 16407764
TI  - Resource sharing in the attentional blink.
AB  - Humans have difficulty processing more than one event at a time, as is evidenced
      by the attentional blink ('blink') phenomenon: the second of two targets in a
      visual stream of events cannot be reported accurately if it appears between 100
      and 500 ms after the first. By using whole-head magnetoencephalography, we show
      that the probability of behaviourally failing to correctly identify the second
      target can be predicted from the amount of attentional resources devoted to
      processing the first target, as indexed by T1 activation. This important finding
      supports resource sharing accounts of divided attention tasks such as the
      'blink'; that is, such tasks may reflect an individual processing strategy rather
      than an immutable structural processing bottleneck.

PMID- 16407765
TI  - Ventromedial prefrontal activity correlates with depressed mood in adolescent
      children.
AB  - In adults, the medial prefrontal cortex and anterior cingulate gyrus are
      preferentially activated during emotion-related processes, including normal
      sadness and pathological depression. It is not clear, however, whether similar
      regional activity is also characteristic of depressed mood during adolescence. We
      correlated whole brain activity during a fear face perception task with scores on
      the Beck Depression Inventory in 16 adolescents undergoing functional magnetic
      resonance imaging. After controlling for age, depressed mood scores correlated
      with increased activity within the ventromedial prefrontal cortex and rostral
      anterior cingulate gyrus, consistent with findings previously reported for
      sadness and depression in adults, suggesting that the neural substrates of
      depressed mood are established early in life and remain relatively consistent
      across development into adulthood.

PMID- 16407766
TI  - Agonist-regulated endocytosis and desensitization of the human nociceptin
      receptor.
AB  - A series of nociceptin receptor ligands has been investigated in relationship to
      their capability to promote receptor endocytosis, desensitization (evaluated as
      inhibition of forskolin-stimulated cAMP production) and compensatory upregulation
      of adenylyl cyclase activity in CHO-K1 cells expressing the cloned human
      nociceptin receptor. Nociceptin (NC), [Arg14, Lys15]NC-NH2 and NNC 63-0532 (0.01
      nM-10 microM) induce a concentration-dependent endocytosis and recycling of the
      nociceptin receptor. This mechanism contributes to maintain receptor signaling as
      it counteracts desensitization development and enhances a compensatory
      upregulation of adenyl cyclase activity. In contrast, the partial agonists
      [Phe1,Psi(CH2NH)Gly2]NC(1-13)-NH2, Ac-RYYRIK-NH2 and Ac-RYYRWK-NH2 (up to 100
      microM) fail to induce receptor endocytosis and cause a pronounced receptor
      desensitization that is not influenced by monensin, a blocker of recycling of the
      internalized receptors.

PMID- 16407767
TI  - Distinct developmental expression of synaptotagmin I and IX in the mouse brain.
AB  - Synaptotagmin IX has been postulated to function as a major Ca2+ sensor for dense
      core vesicle exocytosis in neuroendocrine cells. In this study, we investigated
      the subcellular localization and developmental expression profile of
      synaptotagmin IX in the mouse brain and found that it is mainly present in the
      dense-core vesicle fraction, which is devoid of synaptotagmin I and
      synaptophysin. We also found that the synaptotagmin IX expression level is
      constant throughout the postnatal development of the mouse brain, whereas the
      synaptotagmins I, II, III, VI, and XII are upregulated in parallel with
      synaptogenesis. These findings suggest that synaptotagmin IX regulates the
      transport of certain vesicles in the brain other than synaptic vesicles.

PMID- 16407768
TI  - Oxysterols suppress inducible nitric oxide synthase expression in
      lipopolysaccharide-stimulated astrocytes through liver X receptor.
AB  - Cholesterols are enriched in the brain and can be oxidized to oxysterols by
      several processes. Oxysterols are transport forms of cholesterols across cell
      membranes and the blood-brain barrier. Here, to elucidate the roles of oxysterols
      in brain inflammation, we treated lipopolysaccharide-stimulated rat brain
      astrocytes with two oxysterols, 7-ketocholesterol and 22(R)-hydroxycholesterol.
      Both oxysterols suppressed inducible nitric oxide synthase expression and nitric
      oxide release as well as upstream signaling molecules including interferon-beta,
      phosphorylated signal transducer and activator of transcription 1/3, and
      interferon regulatory factor-1. Oxysterols are known as liver X receptor
      agonists, and inhibitory effects were also observed with synthetic agonists of
      liver X receptor and retinoid X receptor. Thus, we conclude that it is most
      likely mediated by liver X receptor/retinoid X receptor heterodimers.

PMID- 16407769
TI  - Neurite outgrowth in dorsal root ganglia induced by islet neogenesis-associated
      protein peptide involves protein kinase A activation.
AB  - Islet neogenesis-associated protein (INGAP) peptide is a candidate therapeutic
      for diabetes and corrects sensory dysfunction in experimental diabetes in mice.
      In this study, we investigated the mechanism of action by which INGAP peptide
      promotes neurite outgrowth in sensory neurons of the dorsal root ganglia.
      Treatment of dorsal root ganglia primary dispersed cultures with INGAP peptide
      led to the displacement of fluorescently labeled forskolin from adenylate
      cyclase, the cyclic AMP-generating enzyme that has been implicated in
      neuritogenesis. The addition of forskolin or dibutyryl cyclic AMP enhanced the
      effects of INGAP peptide on neurite outgrowth in dorsal root ganglia explant
      cultures. Furthermore, pharmacological inhibition of adenylate cyclase with
      SQ22,536 or of protein kinase A with H89 or KT5720 significantly reduced the
      neurite-promoting effects of INGAP peptide. These results suggest that INGAP
      peptide-induced neurite outgrowth in the dorsal root ganglia partially involves
      cyclic AMP-dependent activation of protein kinase A.

PMID- 16407770
TI  - Retinal ganglion cell axons regenerate in the presence of intact sensory fibres.
AB  - A novel allograft paradigm was used to test whether adult mammalian central axons
      regenerate within a peripheral nerve environment containing intact sensory axons.
      Retinal ganglion cell axon regeneration was compared following anastomosis of
      dorsal root ganglia grafts or conventional peripheral nerve grafts to the adult
      rat optic nerve. Dorsal root ganglia grafts comprised intact sensory and
      degenerate motor axons, whereas conventional grafts comprised both degenerating
      sensory and motor axons. Retinal ganglion cell axons were traced after 2 months.
      Dorsal root ganglia survived with their axons persisting throughout the graft.
      Comparable numbers of retinal ganglion cells regenerated axons into both dorsal
      root ganglia (1053+/-223) and conventional grafts (1323+/-881; P>0.05). The
      results indicate that an intact sensory environment supports central axon
      regeneration.

PMID- 16407771
TI  - Distribution of AAV2-hAADC-transduced cells after 3 years in Parkinsonian
      monkeys.
AB  - The present report describes for the first time, the stability of recombinant
      adeno-associated virus serotype 2 (AAV2) human aromatic L-amino acid
      decarboxylase (hAADC) gene transfer after 3-year survival time in a non-human
      primate model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-lesioned monkeys were treated with six injections of 30
      microl/site of AAV2-hAADC at a concentration of 2 x 10(12) vg/ml into the caudate
      and putamen. Stereological analysis revealed a 46.6% increase in the total number
      of AAV2-hAADC-transduced cells in the striatum between 8 weeks and 3 years after
      gene transfer survival time. In the 8-week animals, the distribution of the AADC+
      cells was dispersed and heterogeneous, whereas in the 3-year animals it was
      widespread and homogenous. Confocal analysis demonstrated that approximately 85%
      of the AADC+ cells were neuronal nuclei immunoreactive.

PMID- 16407772
TI  - Investigating evoked and induced electroencephalogram activity in task-related
      alpha power increases during an internally directed attention task.
AB  - This study sought to explore whether the so-called 'paradoxical' task-related
      increases in the alpha bandwidth of the human electroencephalogram result from
      increases in evoked (phase locked), as opposed to induced (non-phase locked),
      activity. The electroencephalograms of 18 participants were recorded while they
      engaged in both auditory sensory-intake tasks (listening to randomly generated
      'tunes') and internally directed attention tasks (imagining the same randomly
      generated tunes) matched for auditory input. Measures of evoked (phase locked)
      and induced (non-phase locked) activity were compared between tasks. Increases in
      induced alpha power were found during internal attention. No experimental effects
      were observed for evoked activity. These results are not entirely consistent with
      proposals that 'paradoxical' alpha indexes the evoked inhibition of task
      irrelevant processing.

PMID- 16407773
TI  - Widespread functional disconnectivity in schizophrenia with resting-state
      functional magnetic resonance imaging.
AB  - Using resting-state functional magnetic resonance imaging, we examined the
      functional connectivity throughout the entire brain in schizophrenia. The
      abnormalities in functional connectivity were identified by comparing the
      correlation coefficients of each pair of 116 brain regions between 15 patients
      and 15 controls. Then, the global distribution of the abnormal functional
      connectivities was examined. Experimental results indicated, in general, a
      decreased functional connectivity in schizophrenia during rest, and such
      abnormalities were widely distributed throughout the entire brain rather than
      restricted to a few specific brain regions. The results provide a quantitative
      support for the hypothesis that schizophrenia may arise from the disrupted
      functional integration of widespread brain areas.

PMID- 16407774
TI  - Children recruit distinct neural systems for implicit emotional face processing.
AB  - The ability to properly distinguish facial emotions has a protracted development,
      not maturing until well into adolescence. Emotional faces activate emotion
      specific neural networks in adults; whether these networks are operational in
      children is not known. Using an implicit face-processing task in 10-year-old
      children, we determined that the emotions of fear, disgust and sadness recruited
      distinct neural systems. These systems included a number of regions typically
      associated with processing emotions in adults, namely the amygdala and
      parahippocampal gyrus, insula and cingulate gyrus, as well as the fusiform and
      superior temporal gyri. Thus, in spite of immature behavioral responses to
      emotional faces in explicit tasks, neural networks for emotion-specific
      processing are present in young children.

PMID- 16407775
TI  - Pituitary adenylate cyclase-activating polypeptide neurons of the ventromedial
      hypothalamus project to the midbrain central gray.
AB  - The pituitary adenylate cyclase-activating polypeptide (PACAP) and brain-derived
      neurotrophic factor (BDNF) neurons have recently been established as markers of
      the ventromedial hypothalamic nucleus (VMH). However, their neural projections
      from the VMH remained unknown. We examined whether PACAP and BDNF neurons in the
      VMH connected to the mesencephalic central gray (MCG), using the combination of
      in-situ hybridization and immunohistochemical tracing of Fluorogold (FG) injected
      into the MCG. Approximately 49% of PACAP neurons and 19% of BDNF neurons in the
      VMH contained the retrograde-transported FG, and 52% of FG-positive cells were
      PACAP neurons. These results indicate that a large number of PACAP neurons and a
      small number of BDNF neurons of the VMH project to the MCG.

PMID- 16407776
TI  - Fleeting images: rapid affect discrimination in the visual cortex.
AB  - Converging electrophysiological and hemodynamic findings indicate sensory
      processing of emotional pictures is preferred to that of neutral pictures.
      Whereas neuroimaging studies of emotional picture perception have employed
      stimulus durations lasting several seconds, recent electrocortical investigations
      report early visual cortical discrimination between emotionally arousing and
      neutral picture processing. Here, we use a hybrid picture presentation paradigm
      covering a range of rapid presentation rates (0.75-6 Hz), while visual system
      activity is recorded with functional magnetic resonance imaging. Results
      demonstrate widespread sensitivity to emotional arousal in the secondary and
      inferior temporal visual cortex. Furthermore, activity in the lateral inferior
      occipital and medial inferior temporal visual cortex revealed equivalent emotion
      sensitive activation across all presentation rates. Results further support the
      notion that attention and perceptual processing are in part directed by
      underlying motivational systems.

PMID- 16407780
TI  - Murine models of susceptibility to tuberculosis.
AB  - Approximately one third of the world's population is infected with Mycobacterium
      tuberculosis,yet each year a small proportion of those individuals progress to an
      active disease state. Early identification and treatment of such individuals is
      essential to reduce transmission; however, genetic and immunological correlates
      of disease progression have not been well established in man. The murine model
      has been a central tool for the elucidation of protective immune mechanisms that
      are essential for controlling M. tuberculosis infection. Additionally, the study
      of inbred mice has revealed significant divergence in the susceptibility and
      disease progression of individual mouse strains to an infection with
      M.tuberculosis. The continued study of genetically disparate mouse strains has
      the potential to identify immune mechanisms that correlate with increasing
      susceptibility to tuberculosis. These mechanisms will be highly applicable to
      studies in man and assist in the early detection of individuals that are more
      vulnerable to the development of reactivation tuberculosis.

PMID- 16407781
TI  - Immunotherapeutic approaches in ocular inflammatory diseases.
AB  - This comprehensive review discusses immunotherapeutic approaches to ocular
      inflammatory diseases, updates information provided in the literature, and
      presents clinical experiences with an emphasis on autoimmune uveitis at the
      National Eye Institute, United States. Current medical and surgical therapeutic
      approaches, including medications such as corticosteroids, anti-metabolites,
      alkylating agents, calcineurin and purine synthesis inhibitors, biologics as well
      as some anti-infectious agents, are reviewed along with new modalities and
      experimental approaches. Most immunosuppressive therapies have significant
      adverse effects. Physicians must be familiar with the pharmacology of the
      available drugs and aware of the philosophies behind the treatment.

PMID- 16407782
TI  - Roles of galectin-3 in immune responses.
AB  - Galectins are a family of animal lectins with conserved carbohydrate-recognition
      domains for beta-galactoside. Galectin-3 is the only family member that is
      composed of a glycine/prolinerich N-terminal repeated sequence and a C-terminal
      carbohydrate-binding domain.Multiple functions of galectin-3 have been reported,
      depending on its location. Extracellular galectin-3 can bind to cell surface
      through glycosylated proteins and thereby trigger or modulate cellular responses
      such as mediator release or apoptosis. Intracellular galectin-3 has been reported
      to inhibit apoptosis, regulate the cell cycle, and participate in the nuclear
      splicing of pre-mRNA. Recent studies have revealed that galectin-3 is expressed
      in a variety of cell types in the immune system, constitutively or in response to
      microbial invasion. These studies implicate galectin-3 in both innate and
      adaptive immune responses, where it participates in the activation or
      differentiation of immune cells. This review summarizes the roles of galectin-3
      in the immune system and discusses the possible underlying mechanisms.

PMID- 16407783
TI  - Neutrophils in the innate immune response.
AB  - Polymorphonuclear leukocytes (PMNs or neutrophils) are an essential component of
      the human innate immune system. Circulating neutrophils are rapidly recruited to
      sites of infection by host- and/or pathogen-derived components, which also prime
      these host cells for enhanced microbicidal activity. PMNs bind and ingest
      microorganisms by a process known as phagocytosis, which typically triggers
      production of reactive oxygen species and the fusion of cytoplasmic granules with
      pathogen-containing vacuoles. The combination of neutrophil reactive oxygen
      species and granule components is highly effective in killing most bacteria and
      fungi. Inasmuch as PMNs are the most abundant type of leukocyte in humans and
      contain an arsenal of cytotoxic compounds that are non-specific, neutrophil
      homeostasis must be highly regulated. To that end, constitutive PMN turnover is
      regulated by apoptosis, a process whereby these cells shut down and are removed
      safely by macrophages. Notably, apoptosis is accelerated following phagocytosis
      of bacteria, a process that appears important for the resolution of infection and
      inflammation. This review provides a general overview of the role of human
      neutrophils in the innate host response to infection and summarizes some of the
      recent advances in neutrophil biology.

PMID- 16407784
TI  - The biological role and potential therapeutic application of interleukin 7.
AB  - Interleukin (IL)-7 is a pleiotropic, non-redundant cytokine necessary for the
      development of B and T lymphocytes, in particular gammadelta T cell receptor
      positive cell differentiation. The cytokine can function as a cofactor during
      myelopoiesis and the generation of cytotoxic T cells and natural killer cells,
      can activate monocytes/macrophages, and support the survival of mature T cells. A
      role for IL-7 in promoting the formation of Peyer's patch anlage has also been
      demonstrated. IL-7 is constitutively expressed in the thymus, bone marrow stromal
      cells, epithelial and dendritic cells, keratinocytes, as well as in fetal and
      adult liver. IL-7 acts on various cells through its receptor (IL-7R), a
      heterodimer consisting of an alpha chain (CD127) that specifically binds IL-7 and
      a common gamma(c) chain (CD132) shared by other cytokine receptors. The receptor
      is expressed on bone marrow progenitor cells, lymphoid T and B precursors, and
      mature T cells. IL-7 activity towards murine endothelial cells has been recently
      described. The presence of IL-7R on human endothelial cells has also been
      demonstrated. Several therapeutic applications of recombinant IL-7 have been
      proposed. These have focused on the enhancement of lymphopoiesis, promotion of
      stem cell engraftment, and the anti-tumor activity of the cytokine.

PMID- 16407785
TI  - Reactive oxygen intermediates and serum antioxidative system in patients with
      chronic C hepatitis treated with IFN-alpha and thymus factor X.
AB  - INTRODUCTION: In this study, the chemiluminescence (CL) of peripheral blood
      polymorphonuclear leukocytes (PMNLs) and the serum total antioxidative system
      (TAS) were assessed in patients with chronic C hepatitis (CCH) before and after 3
      and 6 months of treatment with interferon (IFN)-alpha and thymus factor X (TFX).
      MATERIAL/METHODS: The study included 26 patients with CCH aged between 25-63
      years (mean: 42.67). Combined therapy with IFN-alpha 2a and a TFX preparation was
      applied. PMNL metabolic activity was assessed applying the whole-blood CL method.
      We measured CL response of neutrophils unstimulated and stimulated by opsonized
      zymosan, N-formyl-methionylleucyl-phenylalanine (N-fMLP), and phorbol-myristate
      acetate (PMA) without and after priming with tumor necrosis factor alpha (10
      ng/ml). The assessment of serum TAS was performed directly before the beginning
      of therapy with IFN-alpha and TFX and after 3 and 6 months of the treatment. A
      colorimetric method based on the reduction of the cationic radical ABTS*(+)
      (cation 2, 2'-azido-bis-[3-ethylobenzothiazolino-6-sulfonate]) in the presence of
      serum antioxidants was used. RESULTS: As a result of the treatment with IFN-alpha
      and TFX, the formation of free oxygen radicals by resting (unprimed) neutrophils
      increased statistically significantly both without stimulation and following
      stimulation by fMLP and PMA. A statistically significant increase in the serum
      antioxidant capacity was observed, which suggests the induction of compensatory
      processes. CONCLUSIONS: Increased in vitro reactive oxygen species production by
      both stimulated and unstimulated peripheral blood neutrophils of patients with
      CCH was observed. Treatment with IFN-alpha and TFX resulted in a compensatory
      increase in serum antioxidative capacity.

PMID- 16407786
TI  - Selective indices on non-specific cell-mediated immunity in rabbits immunized
      with Chlamydophila psittaci.
AB  - INTRODUCTION: Studies of non-specific immunity in infection or immunization with
      Chlamydophila (Chl.) Psittaci in static experimental models showed changes in
      parameters of this immunity. The aim of this study was to evaluate selected
      parameters of non-specific immunity in rabbits immunized with Chl. Psittac.
      MATERIAL/METHODS: The study was performed on rabbits, divided into two groups of
      10 animals each. The rabbits of the first group were immunized with Chl. Psittaci
      strain 6BC and those of the second group were control animals. Blood samples were
      examined 9 times every 7 days. Adherence capacity and ingestion capacity of
      polymorphonuclear (PMN) cells (index of ingestion, percentage of ingestive cells)
      were determined in the blood. The cidal capacity of PMN cells was determined by
      evaluating the reduction of nitroblue tetrazolium test by cytochemical
      (spontaneous and stimulated tests) and spectrophotometric techniques. The
      presence of specific antibodies in the sera was estimated by the complement
      fixation technique RESULTS: Analysis of the results of all the studied parameters
      of non-specific immunity showed tendencies to decrease or increase. These
      differences appeared on days 7-14 and lasted to days 42-56 of the experiment.
      Positive titers of specific antibodies appeared on day 42 after immunization,
      i.e. 5 weeks after the first changes in the parameters of non-specific immunity.
      CONCLUSIONS: The alterations noted in the parameters of non-specific immunity may
      prove useful in determining the condition of a macroorganism in contact with Chl.
      Psittaci.

PMID- 16407787
TI  - Serological classification and epitope specificity of Proteus penneri S29
      lipopolysaccharide.
AB  - INTRODUCTION: Gram-negative bacteria of genus Proteus are common human intestinal
      and urinary tract pathogens. In the genus Proteus there are four clinically
      important named species: P. mirabilis, P. vulgaris, P. penneri, and P. hauseri,
      and three unnamed Proteus genomospecies: 4, 5, and 6. The clinical significance
      of P. penneri, described in 1982 as a new species, is poorly documented. The aim
      of this work is serological characterization and classification of a ceftriaxone
      susceptible P. penneri S29 strain isolated from a 34-year-old patient with
      postneurosurgical meningitis. In this characterization we will also include a
      ceftriaxonresistant strain, P. penneri R15, isolated from the same patient after
      12 days' treatment with ceftriaxon and other antibiotics. MATERIAL/METHODS:
      Rabbit polyclonal O-antisera were obtained against these two strains and purified
      and lipopolysaccharides (LPS) were extracted from the bacterial mass of the P.
      penneri S29 and R15 strains. In the serological investigations the following
      tests were used: enzyme immunosorbent assay (EIA), passive immunohemolysis (PIH),
      inhibition of these tests, absorption of rabbit O-antisera with the respective
      LPS, and repeated PIH, SDS/PAGE, and Western blot techniques. RESULTS: The
      serological studies of the LPS extracted from both P. penneri strains showed the
      identity of both preparations of O-polysaccharides from LPS. In P. penneri S29 O
      antiserum, four different types of antibodies were described and characterized.
      CONCLUSIONS: Both investigated P. penneri S29 and R15 strains were classified to
      the Proteus O31ab serogroup.

PMID- 16407788
TI  - The lunar cycle: effects on human and animal behavior and physiology.
AB  - Human and animal physiology are subject to seasonal, lunar, and circadian
      rhythms. Although the seasonal and circadian rhythms have been fairly well
      described, little is known about the effects of the lunar cycle on the behavior
      and physiology of humans and animals. The lunar cycle has an impact on human
      reproduction, in particular fertility, menstruation, and birth rate. Melatonin
      levels appear to correlate with the menstrual cycle. Admittance to hospitals and
      emergency units because of various causes (cardiovascular and acute coronary
      events, variceal hemorrhage, diarrhea, urinary retention) correlated with moon
      phases. In addition, other events associated with human behavior, such as traffic
      accidents, crimes, and suicides, appeared to be influenced by the lunar cycle.
      However, a number of reports find no correlation between the lunar cycle and
      human reproduction and admittance to clinics and emergency units. Animal studies
      revealed that the lunar cycle may affect hormonal changes early in phylogenesis
      (insects). In fish the lunar clock influences reproduction and involves the
      hypothalamus-pituitary-gonadal axis. In birds, the daily variations in melatonin
      and corticosterone disappear during full-moon days. The lunar cycle also exerts
      effects on laboratory rats with regard to taste sensitivity and the
      ultrastructure of pineal gland cells. Cyclic variations related to the moon's
      phases in the magnitude of the humoral immune response of mice to
      polivinylpyrrolidone and sheep erythrocytes were also described. It is suggested
      that melatonin and endogenous steroids may mediate the described cyclic
      alterations of physiological processes. The release of neurohormones may be
      triggered by the electromagnetic radiation and/or the gravitational pull of the
      moon. Although the exact mechanism of the moon's influence on humans and animals
      awaits further exploration, knowledge of this kind of biorhythm may be helpful in
      police surveillance, medical practice, and investigations involving laboratory
      animals.

PMID- 16407789
TI  - [Role of interleukin 10 in inflammatory response after cardiovascular surgery
      with cardiopulmonary bypass].
AB  - Cardiac surgery (CS) induces a systemic inflammatory response that may be
      implicated in postoperative organ dysfunction. The exposure of blood cells and
      plasma to artificial membranes and the activation of several cell types in the
      setting of ischemia and reperfusion are believed to play an important role in the
      development of this reaction. Various mediators have been reported to be involved
      in the CS-induced reaction, which can lead to postoperative organ dysfunction.
      Understanding the role of these mediators in systemic inflammatory response may
      lead to better prognostic assessment and therapeutic modalities. Interleukin 10
      (IL-10) is a pleiotropic cytokine produced by both T cells and macrophages and
      possesses anti-inflammatory properties. IL-10 circulates in the blood of patients
      undergoing CS with cardiopulmonary bypass (CPB), and increased concentrations of
      IL-10 have been associated with an adverse clinical outcome. The aim of this work
      is to review current know-ledge about the role of IL-10 as a regulator of immune
      response after CS.

PMID- 16407790
TI  - [New therapeutic approach in patients with type 2 diabetes based on glucagon-like
      peptide 1 (GLP-1) and gastric inhibitory peptide (GIP)].
AB  - Inadequate secretion of insulin is a very early element in the development of
      type 2 diabetes and its progression is due to declining beta-cell function. This
      beta-cell defect is partly related to beta-cell loss, but endocrine regulation of
      islet function could also be involved. A number of recent studies have
      highlighted the role of the so-called incretin hormones glucagon-like peptide 1
      (GLP-1) and gastric inhibitory peptide (GIP) in beta-cell function and
      development. Up to two- thirds of the insulin normally secreted in connection
      with meal intake is thought to be due to the insulinotropic actions of these
      hormones. Although patients with type 2 diabetes have been demonstrated to
      exhibit an almost total loss of incretin effect, the glucose-lowering actions of
      exogenous GLP-1 are well preserved. New therapeutic strategies under
      investigation include the search for novel agents able to utilize the incretin
      axis in patients with type 2 diabetes. Two strategies have been applied: the
      first is treatment with GLP-1, either with chronic infusions or with analogues
      with diminished clearance, and the second is inhibiting dipeptidyl peptidase IV,
      the enzyme that inactivates both GLP-1 and GIP in vivo. Inhibition of DP- IV has
      been shown to raise circulating active incretin levels and thus increase the
      effective concentrations of these peptides reaching target tissues. Apart from
      their glucose-dependent manner of stimulating insulin secretion, GLP-1, its
      analogues, and GIP have been demonstrated to stimulate beta-cell growth,
      differentiation, proliferation, and survival. Similarly, studies in both humans
      and in animal models have established DP-IV inhibition as a promising therapeutic
      approach for the treatment of type 2 diabetes, resulting in an enhancement of
      glucose tolerance, insulin sensitivity, and beta-cell glucose responsiveness.

PMID- 16407791
TI  - [The redox system in human semen and peroxidative damage of spermatozoa].
AB  - Epidemiologic studies on male infertility suggest that many cases should be
      considered idiopathic infertility, that is an exact cause of the inability to
      induce conception cannot be identified. Recently it was found that the redox
      status within the male gamete or in the semen can be at least partly responsible
      for the etiology of infertility. Each living cell is capable of producing
      reactive oxygen species (ROS), such as superoxide anion, hydroxyl radical,
      singlet oxygen, or hydrogen peroxide. This process involves the male germ cells
      as well. A certain amount of free radicals generated in the respiratory chain is
      necessary for the normal function of sperm cells. In cases of overproduction of
      ROS, the antioxidant potential of sperm cells can be exhausted and oxidative
      stress may develop. Prolonged exposure of sperm cells to ROS may cause
      peroxidation of the cell membrane lipids, alter the structure of protein
      receptors, enzymes, and transporter proteins, and affect sperm DNA fragmentation.
      This review aims to summarize the current state of knowledge regarding the redox
      system in male sperm and the consequences of oxidative stress on semen quality
      and sperm cell function.

PMID- 16407792
TI  - [Lipoic acid: characteristics and therapeutic application].
AB  - Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA, are present in
      all prokaryotic and eukaryotic cells. Lipoic acid was once considered a vitamin,
      but now it is commonly accepted that it can be synthesized de novo in human
      cells. LA has long been known as a coenzyme of multienzymatic complexes
      catalyzing the decarboxylation of alpha-ketoacids, but the present investigations
      are focused on its antioxidative properties. Both LA and DHLA have proved to be
      potent free radicals scavengers and metal chelators. They are also responsible
      for the regeneration of active forms of other cellular antioxidants, including
      vitamins C and E. Moreover, lipoic acid is involved in the regulation of
      carbohydrate and lipid metabolism. LA is easily absorbed from the
      gastrointestinal tract, is able to cross the blood-brain barrier, and does not
      exhibit any serious side effects. All these features make lipoic acid a very
      promising drug. Nowadays, this compound is used in the treatment of diabetic
      neuropathy, fungi, and metal poisoning, as well as in liver disorders. The
      application of lipoic acid in treating other diseases, including hypertension and
      autoimmunological disorders, needs careful evaluation.

PMID- 16407793
TI  - [The role of mast cells in innate immunity in antibacterial defense].
AB  - Nowadays it is well documented that bacteria and/or their products directly or
      indirectly activate mast cells to secrete mediators and cytokines. These
      mediators and cytokines induce various effects leading to the development of
      local inflammation. Moreover, mast cells have the capacity to bind and
      phagocytose bacteria. What is more, these cells have the capacity to kill
      bacteria. Thus, mast cells play a pivotal role in host defense, especially in
      natural immunity, during bacterial infection.

PMID- 16407794
TI  - [Potentiometric detection of beta-adrenolytic and beta-adrenergic drugs in HPLC
      systems].
AB  - This paper presents a comprehensive review of reference literature and the
      principal results of our own studies on the use of inclusion effects of
      macrocyclic compounds in the potentiometric detection of hypotensive and
      antiarrhythmic drugs as well as bronchodilators following their separation in
      HPLC systems. It was found that the properties of the liquid membrane electrodes
      embodying some macrocyclic compounds (i.e. trioctylated alpha-cyclodextrin,
      dibenzo-18-crown-6 or calix[6]arene hexaethylester) enabled reasonable prediction
      of their sensitivity in terms of the computed hydrophobicity and polarizability
      parameters of the analyzed drugs. The statistically significant equations
      enabling the optimalization of the composition of liquid membrane electrodes and
      the prediction of their detection limits in relation to the molecular structures
      of cationic drugs were established by applying multiparameter regression
      procedures. In particular it was indicated that the use of a liquid membrane
      electrode with trioctylated alpha-cyclodextrin enables sensitive detection (<10(
      8) M) of highly hydrophobic drugs (logP >2.5 on the Parham-Hall-Kier scale) such
      as clenbuterol, bufuralol, and propanolol under HPLC conditions. These results
      indicate that the developed potentiometric detection method of hypotensive drugs
      can be considered as a promising alternative to the immunoassay procedures
      (ELISA) currently recommended for the toxicological determination of trace
      amounts of the drugs in biological samples. It was also shown that the set of
      experimentally determined detection limits characterizing the sensitivity of the
      four different liquid membrane electrodes used in the cation-exchange HPLC system
      enabled reliable screening and proper pharmacological classification of the beta
      adrenergic and beta-adrenolytic drugs analyzed. Using principal component
      analysis (PCA) of the potentiometric data, it was stated that a differentiation
      of cardioselective from non-cardioselective beta1-blockers commonly administered
      as the hypotensive drugs was possible. This result indicates that the new method
      of potentiometric detection in HPLC systems can be applied as an effective high
      throughput screening (HTS) procedure of large combinatorial libraries of newly
      synthesized drug-like candidates. This may increase the possibilities of
      identifying the lead compounds to be directed to further specialized biological
      tests, thus enabling the successful design and formulation of a new generation of
      more selective and pharmacogenome-oriented hypotensive drugs with reduced side
      effects.

PMID- 16407795
TI  - Nec Soli Cedit (article dedicated to Professor Ludwik Hirszfeld).

PMID- 16407796
TI  - [VEGF as an angiogenic, neurotrophic, and neuroprotective factor].
AB  - Vascular endothelial growth factor (VEGF, occurring in several isoforms: VEGF-A, 
      B, -C, -D) is a well-known endothelial cell mitogen and vascular growth and
      permeability factor. Recent work done over the last few years has elucidated the
      important role of VEGF, which participates in the regulation of normal
      (physiological or therapeutic) and pathological angiogenesis (VEGF-A, VEGF-B) and
      lymphangiogenesis (VEGF-C, VEGF-D). VEGF has also been implicated in practically
      every stage of angiogenesis, yet its role in the initiation of new blood vessel
      creation appears to be the most important. In addition to its role as a key
      angiogenic factor, VEGF also possesses neurotrophic and neuroprotective activity
      both in the peripheral and in the central nervous system, exerting a direct
      action on neurons, Schwann cells, astrocytes, neural stem cells, and microglia.
      VEGF interacts with three subtypes of VEGF receptors occurring on the cellular
      membrane known as VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR), and VEGFR-3 (Flt-4). All
      these receptor types possess an internal tyrosin kinase domain. Interaction of
      VEGF with particular subtypes of receptors activates a circuit of signaling
      pathways, e.g. PI3K/Akt, Ras/Raf-MEK/Erk, eNOS/NO, and IP3/Ca2+. These
      participate in the generation of specific biological responses connected with
      proliferation, migration, increasing vascular permeability, or promoting
      endothelial cell survival. Recent findings from experiments performed on animals
      with experimentally evoked focal cerebral ischemia suggest that the
      neuroprotective activity of VEGF runs in parallel with its ability to promote
      neurogenesis and angiogenesis and that these effects may operate independently
      through multiple mechanisms. The above-mentioned three major features
      characterizing the neurobiological activity of VEGF, i.e. neuroprotection,
      neurogenesis, and angiogenesis, together with their possible functional link(s),
      provide the rationale for considering VEGF-based therapy as a promising future
      avenue for a more effective treatment of at least some neurodegenerative
      disorders and stroke. Moreover, the possibility of using neutralizing factors of
      VEGF or VEGF receptor antagonists may reveal a way of preventing many dangerous
      pathologies, including post-ischemic disturbances in cardiac and neurological
      disorders, tumor growth, or hypervascularization in avascular structures of the
      eye.

PMID- 16407797
TI  - [Nitric oxide produced by pulmonary leukocytes in bronchial asthma].
AB  - Nitric oxide (NO) is a multifunctional particle and may play diverse roles in
      physiological and pathological processes. Depending on its concentration, NO can
      be involved in neurotransmission, the regulation of smooth muscle and vascular
      tone, vascular permeability, as well as in immune response. NO is produced by a
      wide variety of cell types and is generated via oxidation of L-arginine,
      catalyzed by the enzyme NO synthase (NOS). Elevated concentrations of NO were
      observed in the exhaled air of asthmatics. Recently, the level of this mediator
      in exhaled air was considered a useful marker in monitoring inflammation as well
      as disease severity and exacerbation in asthma patients. However, the role NO in
      asthma is still unclear. The cellular source of the high concentration of nitric
      oxide in asthma is also not yet certain. Nitric oxide synthases (NOS) were
      localized in a variety of cells of the respiratory tract, including epithelial
      cells, smooth muscle cells, and also pulmonary leukocytes such as macrophages,
      eosinophils, and neutrophils. Most investigators concentrate on epithelial cells
      as a major source of nitric oxide in airways. There is a limited number of
      studies on the production of NO by pulmonary leukocytes. The review presents
      current knowledge on the role of nitric oxide in the process of asthma.

PMID- 16407798
TI  - [Ocular involvement in Epstein-Barr virus infection].
AB  - Epstein-Barr virus (EBV) belongs to the family of herpesviruses. EBV is
      ubiquitous, with high antibody-positive prevalence (up to 90%) in the adult
      population. Clinical manifestations of EBV infection range from subclinical
      seroconversion to the syndrome of infectious mononucleosis. The reported
      manifestations of EBV infection may affect all tissues of the eye. We reviewed
      the ophthalmic manifestations in Epstein-Barr virus infection, concentrating on
      clinical features and laboratory diagnosis.

PMID- 16407799
TI  - [Protocatechuic acid in cancer prevention].
AB  - Protocatechuic acid (3,4-dihydroxybenzoic acid) is a natural phenolic compound
      found in many edible and medicinal plants. Recent studies indicate that it could
      be used as a protective agent against cardiovascular diseases and neoplasms. The
      mechanism of its action is mostly associated with antioxidant activity, including
      inhibition of generation as well as scavenging of free radicals and up-regulating
      enzymes which participate in their neutralization. The influence on phase I and
      II of some carcinogens' metabolism and, perhaps, direct blocking of specific
      binding sites of ultimate carcinogens with DNA molecule, thus preventing adduct
      formation that may result in mutations and neoplastic transformation, are also
      important. However, the other aspects of the chemopreventive activity of
      protocatechuic acid including influence on the activity of inducible isoenzyme of
      cyclooxygenase and nitric oxide synthase or cell cycle regulating proteins are
      not fully evaluated.

PMID- 16407800
TI  - [Adam Opolski (1955-2005)].

PMID- 16407802
TI  - Of anesthesia standards in ambulatory surgery: questions and controversies,
      certainties and prospects.

PMID- 16407803
TI  - Standards of care for ambulatory surgery. Are we up to speed.
AB  - Ambulatory surgeries are becoming increasingly more common in daily anesthesia
      practice, placing greater demands on anesthesia providers to offer timely and
      thorough preoperative evaluation and preparation, optimal patient and surgical
      selection, and efficient, safe, and timely postanesthesia care, all of which
      necessitate an active participation of an anesthesiologist in all aspects of the
      organization and coordination of perioperative management. Numerous studies over
      the last couple of decades have introduced various organizational models for pre
      anesthesia screening, with a goal of improving patient satisfaction, controlling
      the cost, and decreasing surgical delays. Having recognized the importance of
      anesthesia selection regarding patient comfort and the duration of post
      anesthesia recovery in the ambulatory setting, many anesthesiologists have
      focused their attention on studying various anesthesia modalities and techniques
      with new emphasis on preemptive interventions (e.g. preoperative antiemetics,
      continuous peripheral nerve blocks). Finally, a concept of bypassing traditional
      recovery period in the post-anesthesia recovery rooms (''fast tracking'') that
      had been scrutinized over the last decade has been accepted as cost effective and
      safe, providing adequate patient selection.

PMID- 16407804
TI  - Pulmonary capillary pressure. A review.
AB  - Pulmonary capillary pressure (Pcap) is the predominant force that drives fluid
      out of the pulmonary capillaries into the interstitium. Increasing hydrostatic
      capillary pressure is directly proportional to the lung's transvascular
      filtration rate, and in the extreme leads to pulmonary edema. In the pulmonary
      circulation, blood flow arises from the transpulmonary pressure gradient, defined
      as the difference between pulmonary artery (diastolic) pressure and left atrial
      pressure. The resistance across the pulmonary vasculature consists of arterial
      and venous components, which interact with the capacitance of the compliant
      pulmonary capillaries. In pathological states such as acute respiratory distress
      syndrome, sepsis, and high altitude or neurogenic lung edema, the longitudinal
      distribution of the precapillary arterial and the postcapillary venous resistance
      varies. Subsequently, the relationship between Pcap and pulmonary artery
      occlusion pressure (PAOP) is greatly variable and Pcap can no longer be predicted
      from PAOP. In clinical practice, PAOP is commonly used to guide fluid therapy,
      and Pcap as a hemodynamic target is rarely assessed. This approach is potentially
      misleading. In the presence of a normal PAOP and an increased pressure gradient
      between Pcap and PAOP, the tendency for fluid leakage in the capillaries and
      subsequent edema development may substantially be underestimated. Tho-roughly
      validated methods have been developed to assess Pcap in humans. At the bedside,
      measurement of Pcap can easily be determined by analyzing a pressure transient
      after an acute pulmonary artery occlusion with the balloon of a Swan-Ganz
      catheter.

PMID- 16407805
TI  - Subarachnoid anesthesia for loco-regional antiblastic perfusion with circulatory
      block (stop-flow perfusion).
AB  - AIM: Loco-regional antiblastic perfusion with circulatory block (stop-flow
      perfusion, SFP) is a procedure designed to treat solid tumors of the limb and
      pelvis in an advanced stage, like melanoma, sarcoma of the soft tissues and colon
      rectal cancer. The aim of this study was to evaluate if subarachnoid anesthesia
      could represent a safe and suitable anesthetic technique for this procedure.
      METHODS: Thirty SFP procedures were performed in the angiographic room, 15 for
      the treatment of lower-limb neoplasias and 15 for pelvic neoplasias. The patients
      (ASA I-III) had a mean age of 59.1 years (range: 19-81 years). The patients were
      given different dosages of bupivacaine (range: 10-20 mg) in hyperbaric solution
      at the concentration of 0.5% and 1% by lumbar subarachnoid injection at different
      levels (from T12-L1 to L3-L4). Standard monitoring was set up (ECG, pulse
      oximetry, and non-invasive artery pressure). The use of any anesthetic and
      analgesic drug, eventually used in the intra- or postoperative period, was
      recorded. RESULTS: The lumbar puncture was approached at L1-L2 and L2-L3 levels
      in 80% of the cases. Doses of bupivacaine between 12 mg and 14 mg were
      administered in 2/3 of the cases. Bupivacaine was formulated in hyperbaric
      solution and administered at a concentration of 0.5% (8 patients) or 1% (22
      patients). Complica-tions related to the anesthetic technique were absent.
      Intraoperative pain control was almost complete with one exception, when the
      procedure lasted unusually long. Pain control was satisfying immediately after
      the procedure as well: only in 3 cases were non-opiod analgesics administered
      within the first 6 h. CONCLUSIONS: Spinal subarachnoid anesthesia has proven to
      be an effective, safe, and easy-to-manage technique for carrying out SFP
      procedure in a non-conventional environment such as an angiographic room. It was
      free of serious side effects and well tolerated even in patients in poor general
      conditions.

PMID- 16407806
TI  - Complications of epidural and combined spinal-epidural analgesia in labour.
AB  - AIM: The practice of relieving pain during childbirth with epidural or combined
      spinal-epidural analgesia is very widespread in the major Western countries, and
      is increasing in Italy. There are, however, numerous complications of this
      practice for both the woman and the mechanism of the labour. The aim of our study
      was to evaluate the short and long term complications of these techniques in a
      randomised sample of women. METHODS: A randomised, longitudinal, retrospective
      study was carried out in a sample of caucasian nulliparous women who gave birth
      in the second half of 2001. The subjects were divided into 3 groups: Group 1,
      women who gave birth with the aid of epidural analgesia; Group 2, women who
      received combined spinal-epidural analgesia during labour; Group 3, women who
      delivered without any analgesia. The short and long term complications of the 2
      analgesic techniques were compared with those occurring in the control group,
      using Fisher's exact test. RESULTS: The frequency of at least one unwanted effect
      was higher in the 2 groups of women who received analgesia than in the control
      group. Hypotension and pruritus were statistically significantly more frequent in
      the group receiving spinal-epidural analgesia than in the other 2 groups. There
      were no statistically significant differences between the 3 groups in the rates
      of late complications or incidence of deliveries completed by cesarean section.
      CONCLUSIONS: The short-term complications of the analgesic techniques used during
      labour were not very relevant with respect to the subjects' satisfaction
      (excellent in 66% of the women in the group managed with epidural analgesia and
      73% among those treated with the combined spinal-epidural technique). There was
      not a statistically significant difference in the percentage of cesarean
      deliveries in the 3 groups. Epidural and spinal-epidural analgesia to relieve
      pain during labour can, therefore, be considered safe and reliable.

PMID- 16407807
TI  - Patient-controlled analgesia with tramadol versus tramadol plus ketorolac.
AB  - AIM: In this double-blinded, randomized controlled trial, we compared the
      clinical advantages and disadvantages of patient-controlled-analgesia (PCA) with
      continuous infusion (CI) with tramadol alone versus a combination of tramadol
      plus ketorolac in the management of postoperative pain after major abdominal
      surgery. METHODS: Sixty adult patients were randomly assigned to 2 groups. Group
      T, was given 10 mg/mL tramadol and Group TK was given 1.50 mg/mL ketorolac plus 5
      mg/mL tramadol. After an i.v. loading dose of 0.07 mL/kg, the demand bolus
      injection was set at 0.2 mL, with a lockout interval of 30 min, and a continuous
      background i.v. infusion was set at 1.5 mL/h. Data of PCA demand, dose delivered
      and total analgesic consumption were retrieved from the computer memory bank of
      PCA device. Visual analogue scale at rest, sedation score and the occurrence of
      adverse effects were assessed every 3 h for 18 h. RESULTS: No significant
      differences were found with regard to pain scores and side effects. Patients in
      Group TK were significantly more alert. CONCLUSIONS: We concluded that the
      combination of ketorolac plus tramadol in the same PCA device was an effective
      and safe treatment for postoperative analgesia in abdominal surgery.

PMID- 16407808
TI  - Procalcitonin, C-reactive protein, white blood cells and SOFA score in ICU:
      diagnosis and monitoring of sepsis.
AB  - AIM: To determine in critically ill patients the value of procalcitonin (PCT), C
      reactive protein (CRP), sequential organ failure assessment (SOFA) score and
      white blood cell count in diagnosis and monitoring of sepsis. METHODS: Patients
      admitted to a medicosurgical intensive care unit in a prospective, observational
      study, were observed consecutively. According to ACCP/SCCM Consensus Conference
      definition were defined 4 groups: SEPSIS/SS (sepsis, severe sepsis, septic
      shock), SIRS, No-SIRS and TRAUMA. RESULTS: Two hundred and fifty five clinical
      events on a total of 1 826 observation days were observed: 111 SEPSIS/SS, 49
      TRAUMA, 45 SIRS and 50 No-SIRS. ROC values, in the diagnosis of sepsis, were 0.88
      for PCT, 0.74 for CRP, 0.8 for Sepsis score, 0.74 for SOFA, 0.62 for neu
      throphils granulocytes (p<0.05). The best cut-off values in the diagnosis of
      sepsis were 0.47 ng/mL for PCT and 128 mg/L for CRP. PCT and SOFA were higher in
      septic shock than in severe sepsis and sepsis (p<0.05 in all cases). The maximum
      CRP level in SEPSIS/SS was reached only after 24-48 h of observation. Admission
      PCT value of TRAUMA patients whom evolving in septic complication was higher than
      patients with a favourable course: 3.4 ng/mL (range 2.63-12.71) vs 1.2 ng/mL
      (range 0.5-5.2) (p<0.05). TRAUMA patients with septic complications present an
      early and quick significant increase of PCT (p<0.05). CONCLUSIONS: PCT and CRP
      may be useful together with bacteriological data in sepsis diagnosis; PCT and
      SOFA closer correlate with the infection severity; PCT is the better parameter to
      estimate severity, prognosis or further course of the disease.

PMID- 16407809
TI  - Laryngeal mask airway and the Robinow syndrome.
AB  - The Robinow syndrome is an extremely rare congenital syndrome that causes facial
      malformations, as well as genital, cardiac and skeletal abnormalities. Patients
      with this syndrome undergo several operations during their life. Because of the
      facial abnormalities they carry a potential risk for difficult intubation. We
      describe the case of a boy who underwent several operations with documented
      difficult intubation. The laryngeal mask airway provided a good solution for
      airway control and afforded adequate ventilation under both controlled mechanical
      ventilation and spontaneous breathing.

PMID- 16407810
TI  - Uterine rupture and labor analgesia.

PMID- 16407811
TI  - A forum for IRIST.

PMID- 16407813
TI  - A brief history of cell labelling.
AB  - The term cell labelling is usually used in the context of labelled leukocytes for
      imaging inflammation and labelled platelets for imaging thrombosis. Erythrocyte
      labelling for in vitro measurements of red cell life span, in vivo measurements
      of splenic red cell pooling, radionuclide ventriculography and imaging sites of
      bleeding has developed rather separately and has a different history. Labelled
      platelets and leukocytes were originally developed for cell kinetic studies.
      Since the current-day applications of labelled platelets and leukocytes depend on
      a clear understanding of cell kinetics, these classical studies are important and
      relevant to the history of cell labelling.

PMID- 16407814
TI  - Radiolabelled leukocytes for imaging inflammation: how radiochemistry affects
      clinical use.
AB  - Indium-111((111)In)-labelled leukocytes were introduced for imaging inflammation
      about 25 years ago. A few years later methods to label leukocytes with Technetium
      99m ((99m)Tc) were developed, but the two radiolabels cannot be used
      interchangeably. The amount of radioactivity which can be administered with
      (111)In is low, because of its 67-h half-life and associated radiation dose. This
      results in low count density in images. However, (111)In labelling is very
      stable, with binding to intracellular macromolecules and particulates, and there
      is minimal urinary or faecal excretion. In contrast, (99m)Tc has a half-life of 6
      h and can be administered in higher doses, resulting in improved image quality.
      However, (99m)Tc labelling is less stable because the trapped form is soluble and
      there is excretion of (99m)Tc through both the kidneys and intestine, which
      limits imaging of disease in the abdomen except at early times. There is interest
      in extending inflammation imaging to PET. Although leukocytes can be labelled
      with (18)F-FDG, its half-life and stability are not optimal and radiometals such
      as Copper-64 are being evaluated. Despite the laborious nature of leukocyte
      labelling, it has yet to be replaced by direct injection agents.

PMID- 16407816
TI  - Radiolabeled white blood cells and direct targeting of micro-organisms for
      infection imaging.
AB  - Infection imaging is complicated due to multitude of factors interfering with the
      design of radiopharmaceuticals. More than 3 decades ago, labeled leukocytes have
      been introduced for infection imaging and new radiopharmaceuticals have been
      emerging on regular basis. However, labeled leukocytes by in vivo and in vitro
      methods are very effective for diagnosing various lesions such as osteomyelitis,
      cellulitis, diabetic foot, Crohn's disease, inflammatory bowel disease and in
      distinguishing prosthetic infection from loosening of prosthesis. But in vitro
      labeling method using (111)In-oxine, (99m)Tc-HMPAO or (99m)Tc-stannous colloid
      have the inherent limitation of personnel safety risks of infection and cross
      contamination. To overcome these problems, attempts have been made to directly
      target leukocytes by in vivo labeling techniques. There are several receptors
      present on the leukocytes and the granulocytes, which can be targeted with
      suitable ligands. These will include anti-NCA90-Fab, murine MoAb IgG(1) that is
      cross-reactive to antigen 95 on neutrophils, anti-CD15 antigen and DPC-11870 that
      targets the leukotriene B4 receptors of granulocytes. In a new approach, (99m)Tc
      labeled ciprofloxacin has been developed to directly target ''live bacteria'' to
      detect infection by in vivo method. This approach showed considerable promise in
      the preliminary studies but clinical trials showed limitations. Analogs of a
      natural mammalian antimicrobial agents, such as Ubiquicidin were successful in
      animal studies and have now entered clinical trials. (99m)Tc-labeled fluconazole
      (a fungal antibiotic) and labeled Chitinase ((123)I-ChiB_E144Q), have been
      developed to detect fungal infection. The ability to distinguish between fungal
      and bacterial infection is considered important, as patients undergoing
      chemotherapy are prone to fungal infection. Undoubtedly, the new trends and new
      radiopharmaceuticals developed for infection and inflammation imaging have
      contributed towards a better understanding of the underlying processes.

PMID- 16407815
TI  - The radiopharmaceutical chemistry of 99mTc-tin fluoride colloid-labeled
      leukocytes.
AB  - Tc-99m-tin fluoride colloid is a radiotracer used to label patient white cells,
      for the diagnosis of infection and inflammation. The scintigraphic technique has
      been employed in routine clinical practice for approximately 20 years in
      Australia, yet the chemistry of the radiolabeling agent, and the physiological
      distribution of (99m)Tc-leukocytes, are not entirely understood. In this review,
      the physico-chemical characteristics of (99m)Tc-tin fluoride colloid are
      discussed, as well as the in vitro and in vivo distribution of (99m)Tc-tin
      fluoride-labeled-leukocytes. Furthermore, important animal and human studies are
      summarized, that emphasize the clinical usefulness of this radiopharmaceutical
      tracer in nuclear medicine today.

PMID- 16407817
TI  - In vivo tracking for cell therapies.
AB  - The success of a particular cellular therapy regime requires the therapeutic
      agent to migrate expeditiously to the intended target in sufficient numbers and
      to provoke a desirable response. There are many variables associated with the
      production, administration and host that need to be investigated to maximize the
      resulting therapeutic benefit. The large number of factors which may contribute
      to, or detract from, treatment efficacy can make therapy optimization an arduous
      procedure. Direct visualization of in vivo migration patterns using nuclear
      medicine techniques greatly assists the appraisal of the multitude of variables.
      Conventional radionuclide cell labeling is a proven, simple and sensitive
      technique which can provide whole body biodistribution information. Labeling with
      a PET isotope offers greater sensitivity, much improved 3-dimensional resolution
      and quantification. In general, current efforts are increasingly concentrating on
      this technology. Imaging studies can supply definitive evidence of successful
      targeting and allow quantification of the degree of migration to a particular
      site. Incorporating tracking studies into clinical trials of cell-based therapy
      at the earliest stage can provide proof of mechanism of the therapy and permit
      evaluation of the many contributory variables, even on a patient-by-patient
      basis.

PMID- 16407818
TI  - Imaging reporter genes for cell tracking with PET and SPECT.
AB  - Transplantation of cells into damaged tissue has tremendous therapeutic potential
      in a number of disorders, such as Parkinson's disease and myocardial infarction.
      Positron emission tomography (PET) and single photon emission tomography (SPECT)
      are highly sensitive imaging modalities, which can detect and track these
      cellular implants through a number of mechanisms. The stable transfection of
      cells with a reporter gene, which can be visualized using a radioactive PET or
      SPECT reporter probe, allows the repeated visualization of the migration and
      function of cells. These imaging techniques can be used to assess cell
      trafficking with methods that are easily translatable to humans. This review
      describes several reporter genes for PET and SPECT, and compares them against
      other techniques and imaging modalities.

PMID- 16407819
TI  - Assessing cell trafficking by noninvasive imaging techniques: applications in
      experimental tumor immunology.
AB  - Tracer methods are increasingly being exploited to examine the trafficking
      patterns of cells transferred into recipient models of diseases, to optimize
      immune cell therapies, and to assess cancer gene therapy and vaccines in various
      cancer models. In animal cancer models, noninvasive monitoring by imaging tumor
      response could significantly facilitate the development of immune cell therapies
      against cancer. Currently, ex vivo lymphocyte labeling is primarily done by
      direct labeling. Major advances in cell labeling procedures have led to the use
      of reporter constructs to assess gene expression in vivo. With this novel
      technique, the reporter gene marks the cell with a specific protein that
      distinguishes the cell and its cellular progeny from other cells after migration,
      homing and mitosis. Several in vivo imaging procedures, including positron
      emission tomography, single photon emission tomography and magnetic resonance
      imaging, have been rescaled for studies in small animals. Other methods initially
      used for in vitro bioluminescence and fluorescence studies have also been refined
      for in vivo studies. When combined, these methods allow to assess cell
      trafficking in a noninvasive fashion, beyond lymphocyte response to inflammation,
      including metastatic diffusion and stem cell transplantation.

PMID- 16407820
TI  - Upregulation and activation of PKC alpha by ErbB2 through Src promotes breast
      cancer cell invasion that can be blocked by combined treatment with PKC alpha and
      Src inhibitors.
AB  - Although ErbB2 is known to enhance breast cancer metastasis, the signaling events
      responsible for this remain elusive. Alpha-isozyme of protein kinase C
      (PKCalpha), which is involved in cancer development and progression, has been
      suggested to be activated by ErbB2 without direct evidence. In addition, the
      roles of PKCalpha in ErbB2-mediated cancer cell malignancy have not been clearly
      identified. In this study, we investigated whether ErbB2 can activate PKCalpha
      and determined what role PKCalpha plays in ErbB2-mediated breast cancer cell
      invasion. We expressed wild-type and mutant ErbB2 with altered signaling
      capacities in MDA-MB-435 breast cancer cells and revealed that overexpression or
      activation of ErbB2 in MDA-MB-435 cells upregulated and activated PKCalpha and
      that downregulation of ErbB2 by small-interfering RNA decreased the expression
      and activity of PKCalpha in BT474 breast cancer cells. These in vitro results
      were supported by data from breast cancer patient samples. In 150 breast cancer
      tumor samples, ErbB2-overexpressing tumors showed significantly higher positive
      rates of PKCalpha membrane immunohistochemistry staining than that of ErbB2-low
      expressing tumors. Mechanistically, we found that PKCalpha is co
      immunoprecipitated with Src and PKCalpha expression and activity can be decreased
      by Src inhibitor PP2 and by the expression of a dominant-negative mutant of Src.
      Moreover, ErbB2-mediated upregulation of urokinase-type plasminogen activator
      receptor (uPAR) is reduced by either the PKCalpha inhibitor Go6976 or the Src
      inhibitor PP2, and the combination of Go6976 with PP2 is superior to either agent
      alone in suppressing uPAR expression and cell invasion. These results demonstrate
      that PKCalpha is critical for ErbB2-mediated cancer cell invasion and provide
      valuable insights for current and future PKCalpha and Src inhibitor clinical
      trials.

PMID- 16407821
TI  - Hypoxia induced by benign intestinal epithelial cells is associated with
      cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway.
AB  - Cyclooxygenase-2 (COX-2) plays important roles in tumor development. Especially
      in the early-stage colorectal tumors, COX-2 expression is often observed in the
      tumor stroma. However, the mechanism regulating such stromal expression of COX-2
      remains unknown. In the present study, we simulated the indirect interaction
      between epithelial cells and stromal cells in the process of colorectal tumor
      development using an in vitro co-culture model in which NIH3T3 fibroblasts were
      co-cultured with 'sparsely' or 'densely' populated intestinal epithelial cells,
      Intestine-407 as a model of premalignant or benign intestinal epithelial cells,
      and DLD-1 and Caco-2 as models of malignant epithelial cells. COX-2 expression in
      NIH3T3 fibroblasts was upregulated when co-cultured with the 'dense' epithelial
      cells regardless of their character. Interestingly, there was pericellular
      hypoxia in the vicinity of NIH3T3 fibroblasts when co-cultured with 'dense'
      epithelial cells, and the recovery of the partial pressure of oxygen level
      resulted in the reduction of enhanced COX-2 expression only in NIH3T3 fibroblasts
      co-cultured with 'dense' Intestine-407 cells. Furthermore, COX-2 expression was
      also reduced by the inhibition of transcription factor AP-1. Thus, pericellular
      hypoxia of the stromal cells caused by densely populated epithelial cells may be
      one of the potent COX-2 enhancers before completion of malignant transformation
      during intestinal tumor development.

PMID- 16407822
TI  - Integrin-linked kinase activity is associated with interleukin-1 alpha-induced
      progressive behavior of pancreatic cancer and poor patient survival.
AB  - Cancer cell adhesion and invasion into extracellular matrix are regulated by
      integrin-linked kinase (ILK) activity in a phosphatidylinositol 3-kinase (PI3-K)
      dependent manner. In this study, we demonstrated that ILK and beta(1)-integrin
      play important roles in interleukin (IL)-1alpha-induced enhancement of adhesion
      and invasion of pancreatic cancer cells through p38 mitogen-activated protein
      kinase (MAPK) signaling pathway and activator protein-1 (AP-1) activation.
      Alteration of ILK kinase activity controlled IL-1alpha-induced p38 MAPK
      phosphorylation and its downstream AP-1 activation with subsequent regulation of
      pancreatic cancer cell adhesion and invasion. Overexpressed ILK enhances the IL
      1alpha-induced p38 MAPK phosphorylation more strongly through glycogen synthase
      kinase 3 (GSK-3) activation, and subsequently induces AP-1 activation, which
      promotes aggressive capabilities of pancreatic cancer cells. In contrast,
      knockdown of ILK kinase activity inhibits the IL-1alpha-induced activation of
      MAPK/AP-1 pathway via inhibition of GSK-3 phosphorylation. In immunohistochemical
      analysis, statistically significant association between strong expression of ILK
      and poor prognosis of pancreatic cancer patients were observed, and strong
      expression of ILK in cancerous tissues can be a significant prognostic indicator
      of pancreatic cancer patients. Our results suggest that ILK is involved with
      aggressive capability in pancreatic cancer and that these regulations can be
      helpful to understand biological processes for a better translational treatment
      for pancreatic cancer patients.

PMID- 16407823
TI  - A crosstalk between the Wnt and the adhesion-dependent signaling pathways governs
      the chemosensitivity of acute myeloid leukemia.
AB  - Relapses following chemotherapy are a major hindrance to patients' survival in
      acute myeloid leukemia (AML). To investigate the role of the hematopoietic niche
      in the chemoresistance of leukemic cells, we examined two pathways: one mediated
      by adhesion molecules/integrins, and the other by soluble factors of the
      morphogen Wnt pathway. In our study, both the adhesion of leukemic blasts to
      fibronectin and the addition of Wnt antagonists induced, independently,
      resistance of AML cells to daunorubicin in a cell survival assay. Using
      pharmacological inhibitors and siRNA, we showed that both resistance pathways
      required the activity of the glycogen synthase kinase 3beta (GSK3beta). Moreover,
      the AML cell protection downstream of GSK3beta was mediated by NF-kappaB. A link
      between the adhesion and the Wnt pathway was found, as adhesion of U937 on human
      osteoblasts, a component of the hematopoietic niche, triggered the secretion of
      the Wnt antagonist sFRP-1 and supported resistance to daunorubicin. The
      osteoblast-conditioned medium could also confer chemoresistance to U937 cells
      cultured in suspension, and this cell protective effect was abrogated after
      depletion of sFRP-1. In the context of this potential double in vivo resistance,
      modulators of the common signal GSK3beta and of its target NF-kappaB could
      represent important novel therapeutic tools.

PMID- 16407824
TI  - Localization of a susceptibility locus for hepatocellular carcinoma to chromosome
      4q in a hepatitis B hyperendemic area.
AB  - Chromosome 4q is one of the most common regions with a high frequency of allelic
      loss in hepatocellular carcinoma (HCC). To identify the HCC-susceptibility locus
      on chromosome 4q, we have performed linkage and family-based association analyses
      on Chinese families with HCC from Taiwan, where hepatitis B is hyperendemic.
      Using 77 microsatellite markers spanning chromosome 4q on 52 multiplex families,
      we found suggestive evidence of linkage to 4q22.3-28.1 with a maximum two-point
      heterogeneity LOD (HLOD) score of 2.55 at marker D4S3240 on chromosome 4q25.
      Multipoint analyses with microsatellite markers in the region 4q22.3-28.1
      resulted in a maximum HLOD score of 3.12 and a maximum nonparametric linkage
      (NPL) Z score of 1.98 (pointwise P=0.0080; region-wide empirical P=0.021) for
      D4S3240. The evidence for linkage to D4S3240 was seen mostly in a subset of 28
      families lacking affected parents, which showed multipoint HLOD and NPL scores of
      3.25 and 2.79 (pointwise P=0.0028; region-wide empirical P=0.008), respectively.
      Family-based association analyses of the 77 microsatellite markers in 191
      families (53 multiplex plus 138 singleton families) using the pedigree
      disequilibrium test provide further support for observed linkage. Additional
      genotyping in the 52 multiplex families informative for linkage analyses was
      performed for 29 single-nucleotide polymorphisms around D4S3240. A common
      haplotype (at markers rs7442180 and rs221330) positioned approximately 873 kb
      away from D4S3240 was associated with HCC, with P=0.0074.

PMID- 16407825
TI  - Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous
      recombination, independently of apoptosis regulation.
AB  - In order to analyse the relationships between regulation of apoptosis and
      homologous recombination (HR), we overexpressed proapoptotic Bax or only-BH3 Bid
      proteins or antiapoptotic Bcl-2 or Bcl-XL, in hamster CHO cells or in SV40
      transformed human fibroblasts. We measured HR induced by gamma-rays, UVC or a
      specific double-strand cleavage targeted in the recombination substrate by the
      meganuclease I-SceI. We show here that the induction of both recombinant cells
      and recombinant colonies was impaired when expressing Bcl-2 family members, in
      hamster as well as in human cells. Moreover, the pro- as well as antiapoptotic
      Bcl-2 family members inhibited HR, independently of degradation of the RAD51
      recombination protein and of their impact on apoptosis. These data reveal a
      mechanism of HR downregulation by potentially proapoptotic proteins, distinct
      from and parallel to degradation of recombination proteins, a situation that
      should also optimize the efficiency of programmed cell death.

PMID- 16407826
TI  - Overexpression of hRFI inhibits 5-fluorouracil-induced apoptosis in colorectal
      cancer cells via activation of NF-kappaB and upregulation of BCL-2 and BCL-XL.
AB  - Resistance to apoptosis is one of the important determinants of resistance to 5
      fluorouracil (5-FU) in colorectal cancer cells. Human Ring-Finger homologous to
      Inhibitor of apoptosis protein type (hRFI) is a newly discovered gene that has
      been shown to inhibit death receptor-mediated apoptosis in colorectal cancer
      cells. However, the molecular mechanism of the inhibition of apoptosis is
      presently unknown. In order to investigate the molecular function of hRFI in the
      regulation of 5-FU-induced apoptosis in colorectal cancer cells, HCT116 cells
      were stably transfected with hRFI or LacZ as a control. hRFI overexpression
      resulted in cellular resistance to 5-FU through an inhibition of the
      mitochondrial apoptotic pathway and specific upregulation of Bcl-2 and Bcl-XL.
      Futhermore, hRFI overexpression resulted in the activation of nuclear factor
      kappaB (NF-kappaB). Inhibition of NF-kappaB effectively reversed the resistance
      to apoptosis as well as the upregulation of Bcl-2 and Bcl-XL in the hRFI
      transfectant, indicating that the activation of NF-kappaB is the key mechanism
      for all these findings. Overexpression of hRFI in SW480 and COLO320 colorectal
      cancer cells similarly resulted in resistance to 5-FU with the activation of NF
      kappaB and upregulation of Bcl-2 and Bcl-XL. hRFI might be a novel therapeutic
      target for gene therapy in colorectal cancer.

PMID- 16407828
TI  - The insulin-like growth factor-1 receptor inhibitor PPP produces only very
      limited resistance in tumor cells exposed to long-term selection.
AB  - The cyclolignan PPP was recently demonstrated to inhibit the activity of insulin
      like growth factor-1 receptor (IGF-1R), without affecting the highly homologous
      insulin receptor. In addition, PPP caused complete regression of xenografts
      derived from various types of cancer. These data highlight the use of this
      compound in cancer treatment. However, a general concern with antitumor agents is
      development of resistance. In light of this problem, we aimed to investigate
      whether malignant cells may develop serious resistance to PPP. After trying to
      select 10 malignant cell lines, with documented IGF-1R expression and apoptotic
      responsiveness to PPP treatment (IC50s less than 0.1 microM), only two survived
      an 80-week selection but could only tolerate maximal PPP doses of 0.2 and 0.5
      microM, respectively. Any further increase in the PPP dose resulted in massive
      cell death. These two cell lines were demonstrated not to acquire any essential
      alteration in responsiveness to PPP regarding IGF-1-induced IGF-1R
      phosphorylation. Neither did they exhibit any increase in expression of the
      multidrug resistance proteins MDR1 or MRP1. Consistently, they did not exhibit
      decreased sensitivity to conventional cytostatic drugs. Rather, the sensitivity
      was increased. During the first half of the selection period, both cell lines
      responded with a temporary and moderate increase in IGF-1R expression, which
      appeared to be because of an increased transcription of the IGF-1R gene. This
      increase in IGF-1R might be necessary to make cells competent for further
      selection but only up to a PPP concentration of 0.2 and 0.5 microM. In
      conclusion, malignant cells develop no or remarkably weak resistance to the IGF
      1R inhibitor PPP.

PMID- 16407827
TI  - The elucidation of novel SH2 binding sites on PLD2.
AB  - Our laboratory has recently reported that the enzyme phospholipase D2 (PLD2)
      exists as a ternary complex with PTP1b and the growth factor receptor bound
      protein 2 (Grb2). Here, we establish the mechanistic underpinnings of the
      PLD2/Grb2 association. We have identified residues Y(169) and Y(179) in the PLD2
      protein as being essential for the Grb2 interaction. We present evidence
      indicating that Y(169) and Y(179) are located within two consensus sites in PLD2
      that mediate an SH2 interaction with Grb2. This was demonstrated with an SH2
      deficient GSTGrb2 R86K mutant that failed to pull-down PLD2 in vitro. In order to
      elucidate the functions of the two neighboring tyrosines, we created a new class
      of deletion and point mutants in PLD2. Phenylalanine replacement of Y(169) (PLD2
      Y169F) or Y(179) (PLD2 Y179F) reduced Grb2 binding while simultaneous mutation
      completely abolished it. The role of the two binding sites on PLD2 was found to
      be functionally nonequivalent: Y(169) serves to modulate the activity of the
      enzyme, whereas Y(179) regulates total tyrosine phosphorylation of the protein.
      Interestingly, binding of Grb2 to PLD2 occurs irrespectively of lipase activity,
      since Grb2 binds to catalytically inactive PLD2 mutants. Finally, PLD2 residues
      Y(169) and Y(179) are necessary for the recruitment of Sos, but only
      overexpression of the PLD2 Y179F mutant resulted in increased Ras activity,
      p44/42(Erk) phosphorylation and enhanced DNA synthesis. Since Y(169) remains able
      to modulate enzyme activity and is capable of binding to Grb2 in the PLD2 Y179F
      mutant, we propose that Y(169) is kept under negative regulation by Y(179). When
      this is released, Y(169) mediates cellular proliferation through the Ras/MAPK
      pathway.

PMID- 16407829
TI  - Alterations of the Wnt signaling pathway during the neoplastic progression of
      Barrett's esophagus.
AB  - Aberrant activation of the Wnt signaling pathway has been reported during
      neoplastic progression in Barrett's esophagus (BE). However, mutations in APC and
      CTNNB1 genes were rarely observed. In this study, expression pattern of Wnt
      ligands, Frizzled receptors and APC, as well as the methylation status of the
      APC, SFRP1 and SFRP2 promoter genes were investigated in normal esophageal mucosa
      and in preneoplastic and neoplastic lesions of BE patients. Promoter methylation
      of APC was found in all BE samples and in 95% of esophageal adenocarcinomas
      (EAC). Full methylation of APC correlated with lack of expression. In EAC,
      nuclear translocation of beta-catenin was observed regardless of the expression
      of APC. WNT2 expression was higher in dysplasia and EAC than in BE, with 20/26
      (77%) of the EAC showing high expression of WNT2. SFRP1 methylation occurred in
      all BE samples and in 96% of EAC, while SFRP2 was methylated in 73% of the normal
      squamous esophageal mucosa samples. In conclusion, (1) alterations of key
      regulators of the Wnt signaling are frequent in the pathogenesis of BE; (2) the
      APC and SFRP1 genes are inactivated by promoter methylation in BE; (3) the WNT2
      gene is upregulated along the progression from low-grade dysplasia to EAC.

PMID- 16407830
TI  - MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix
      metalloproteinase type 2 activation and cell invasion in human prostate cancer.
AB  - Although cell invasion is a necessary early step in cancer metastasis, its
      regulation is not well understood. We have previously shown, in human prostate
      cancer, that transforming growth factor beta (TGFbeta)-mediated increases in cell
      invasion are dependent upon activation of the serine/threonine kinase, p38 MAP
      kinase. In the current study, downstream effectors of p38 MAP kinase were sought
      by first screening for proteins phosphorylated after TGFbeta treatment, only in
      the absence of chemical inhibitors of p38 MAP kinase. This led us to investigate
      mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2), a known
      substrate of p38 MAP kinase, as well as heat-shock protein 27 (HSP27), a known
      substrate of MAPKAPK2, in both PC3 and PC3-M human prostate cells. After
      transient transfection, wild-type MAPKAPK2 and HSP27 both increased TGFbeta
      mediated matrix metalloproteinase type 2 (MMP-2) activity, as well as cell
      invasion, which in turn was inhibited by SB203580, an inhibitor of p38 MAP
      kinase. Conversely, dominant-negative MAPKAPK2 blocked phosphorylation of HSP27,
      whereas dominant-negative MAPKAPK2 or mutant, non-phosphorylateable, HSP27 each
      blocked TGFbeta-mediated increases in MMP-2, as well as cell invasion. Similarly,
      knock down of MAPKAPK2, HSP27 or both together, by siRNA, also blocked TGFbeta
      mediated cell invasion. This study demonstrates that both MAPKAPK2 and HSP27 are
      necessary for TGFbeta-mediated increases in MMP-2 and cell invasion in human
      prostate cancer.

PMID- 16407831
TI  - TIMP-1 regulation of cell cycle in human breast epithelial cells via
      stabilization of p27(KIP1) protein.
AB  - Increasing evidence suggests that tissue inhibitor of metalloproteinases-1 (TIMP
      1) can directly regulate cell growth and apoptosis independent of its matrix
      metalloproteinases (MMPs)-inhibitory activity. While TIMP-1's antiapoptotic
      activity has been well demonstrated, conflicting data has been reported regarding
      TIMP-1's role in growth regulation. Here we show that TIMP-1 reduces the growth
      rate of human breast epithelial (MCF10A) cells by inducing cell cycle arrest at
      G(1). TIMP-1-mediated cell cycle arrest is associated with its downregulation of
      cyclin D(1) and upregulation of p27(KIP1), resulting in inhibition of cyclin
      dependent kinase activity necessary for phosphorylation of the tumor suppressor
      retinoblastoma protein. We further show that TIMP-1 modulation of cyclin D(1) and
      p27(KIP1) is achieved through TIMP-1-mediated differential regulation of protein
      stability independent of growth factor signaling. We also show that TIMP-1
      mediated differential regulation of cyclin D(1) and p27(KIP1) is independent of
      cell adhesion signaling. Whereas approximately 50% of MCF10A cells with reduced
      TIMP-1 expression underwent cell death following loss of cell adhesion (anoikis),
      TIMP-1 overexpressing cells remained viable with prominent cell cycle arrest
      without detectable cell death. Taken together, we propose that TIMP-1-mediated
      cell survival independent of cell adhesion is accompanied with cell cycle arrest
      in human breast epithelial cells, although cell cycle regulation may not be a
      prerequisite for TIMP-1 regulation of apoptosis in general.

PMID- 16407832
TI  - Genome-wide profiling of promoter methylation in human.
AB  - DNA methylation in the promoter region of a gene is associated with a loss of
      that gene's expression and plays an important role in gene silencing. The
      inactivation of tumor-suppressor genes by aberrant methylation in the promoter
      region is well recognized in carcinogenesis. However, there has been little study
      in this area when it comes to genome-wide profiling of the promoter methylation.
      Here, we developed a genome-wide profiling method called Microarray-based
      Integrated Analysis of Methylation by Isoschizomers to analyse the DNA
      methylation of promoter regions of 8091 human genes. With this method, resistance
      to both the methylation-sensitive restriction enzyme HpaII and the methylation
      insensitive isoschizomer MspI was compared between samples by using a microarray
      with promoter regions of the 8091 genes. The reliability of the difference in
      HpaII resistance was judged using the difference in MspI resistance. We
      demonstrated the utility of this method by finding epigenetic mutations in
      cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes.
      Using this method, we found that frequency of the aberrant promoter
      hypermethylation in cancer is higher than previously hypothesized. Aberrant
      hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide
      analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC
      ratio of these sequences, suggesting that CpG-poor genes are sensitive to
      demethylation activity in cancer.

PMID- 16407833
TI  - Interplay between VHL/HIF1alpha and Wnt/beta-catenin pathways during colorectal
      tumorigenesis.
AB  - Activation of the Wnt signaling pathway initiates the transformation of
      colorectal epithelial cells, although the transition to metastatic cancer
      requires angiogenesis. We have investigated the expression of the von Hippel
      Lindau (VHL) tumor suppressor in the intestines from humans and mice. Here, we
      show that VHL expression is regulated by TCF4 and is restricted to the
      proliferative compartment at the bottom of intestinal crypts. Accordingly, VHL is
      completely absent from the proliferative intestinal pockets of Tcf4(-/-)
      perinatal mice. We observed complementary staining of the hypoxia-inducible
      factor (HIF) 1alpha to VHL in normal intestinal epithelium as well as in all
      stages of colorectal cancer (CRC). To the best of our knowledge, this is the
      first report demonstrating the presence of nuclear HIF1alpha in normoxic healthy
      adult tissue. Although we observed upregulated levels of VHL in very early CRC
      lesions from sporadic and familial adenomatous polyposis patients - presumably
      due to activated Wnt signaling - a clear reduction of VHL expression is observed
      in later stages of CRC progression, coinciding with stabilization of HIF1alpha.
      As loss of VHL in later stages of CRC progression results in stabilization of
      HIF, these data provide evidence that selection for VHL downregulation provides a
      proangiogenic impulse for CRC progression.

PMID- 16407834
TI  - Cbl escapes Cdc42-mediated inhibition by downregulation of the adaptor molecule
      betaPix.
AB  - The Pix/Cool proteins are involved in the regulation of cell morphology by
      binding to small Rho GTPases and kinases of the Pak family. Recently, it has been
      shown that betaPix/Cool-1 associates with the ubiquitin ligase Cbl, which appears
      to be a critical step in Cdc42-mediated inhibition of epidermal-growth-factor
      receptor (EGFR) ubiquitylation and downregulation. Here we show that the SH3
      domain of betaPix specifically interacts with a proline-arginine motif (PxxxPR)
      present within the ubiquitin ligase Cbl and Pak1 kinase. Owing to targeting of
      the same sequence, Cbl and Pak1 compete for binding to betaPix. In this complex,
      Cbl mediates ubiquitylation and subsequent degradation of betaPix. Our findings
      reveal a double feedback loop in which the Cdc42/betaPix complex blocks Cbl's
      ability to downregulate EGFR, while Cbl in turn promotes degradation of betaPix
      in order to escape this inhibition. Such a relationship provides a mechanism to
      fine-tune the kinetics of RTK endocytosis and degradation depending on the pool
      of active Cdc42 and the duration of EGFR signaling.

PMID- 16407835
TI  - Homotypic association between tumour-associated VHL proteins leads to the
      restoration of HIF pathway.
AB  - The von Hippel-Lindau (VHL) tumour suppressor gene encodes a substrate-specifying
      component of an E3 ubiquitin ligase that targets hypoxia-inducible factor (HIF)
      alpha subunits for degradation under normoxia. The VHL protein is composed of an
      N-terminal HIFalpha-binding beta domain and a C-terminal alpha domain, which is
      necessary and sufficient for the formation of the E3 multiprotein enzyme. A large
      number of disease-causing mutations in either the alpha or beta domain renders
      HIFalpha stable irrespective of oxygen tension, leading to the upregulation of
      numerous HIF-target genes, such as GLUT1 and VEGF. Here, we show that VHL forms a
      self-associated complex in vivo, but not in vitro, and demonstrate that
      coexpression of two different VHL missense mutants -- one in the alpha domain and
      the other in the beta domain -- restores HIF-mediated gene expression profile.
      These findings indicate that VHL homotypic complexes can function in vivo in a
      complementary fashion to target HIFalpha for ubiquitin-mediated proteolysis, and
      potentially explain why VHL-associated tumours with a missense mutation-carrying
      VHL allele is almost invariably accompanied by a second VHL allele harbouring a
      gross truncation or deletion.

PMID- 16407836
TI  - p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice.
AB  - Analysis of the INK4A/ARF locus in human T-ALL patients revealed frequent
      deletions in exon 2, the exon common to both p16(INK4A) and p14(ARF). Other
      studies have described selective deletion of exon 1beta of p14(ARF) or
      methylation of the p16(INK4A) promoter. Therefore, it is unclear from these
      studies whether loss of p16(INK4A) and/or p14(ARF) contributes to the development
      of T-ALL. To elucidate the relative contribution of the ink4a/arf locus to T-cell
      leukemogenesis, we mated our tal1 transgenic mice to ink4a/arf-/-, p16(ink4a)-/-,
      and p19(arf)-/- mice and generated tal1/ink4a/arf+/-, tal1/p16(ink4a)+/-, and
      tal1/p19(arf)+/- mice. Each of these mice developed T-cell leukemia rapidly,
      indicating that loss of either p16(ink4a) or p19(arf) cooperates with Tal1 to
      induce leukemia in mice. Preleukemic studies reveal that Tal1 expression
      stimulates entry into the cell cycle and thymocyte apoptosis in vivo.
      Interestingly, mice expressing a DNA-binding mutant of Tal1 do not exhibit
      increases in S phase cells. The S phase induction is accompanied by an increase
      in thymocyte apoptosis in tal1 transgenic mice. Whereas apoptosis is reduced to
      wild-type levels in tal1/ink4a/arf-/- mice, S phase induction remains unaffected.
      Thus, Tal1 stimulates cell cycle entry independent of the ink4a/arf locus, but
      its ability to induce apoptosis is Ink4a/Arf-dependent.

PMID- 16407837
TI  - A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition
      in head and neck squamous cell carcinoma.
AB  - To investigate whether genetic alteration of the STK11 (serine/threonine kinase
      11)/LKB1 tumor-suppressor gene is involved in the carcinogenesis of head and neck
      squamous cell carcinoma (HNSCC), the entire encoding exons and flanking intronic
      sequences of the STK11/LKB1 gene were analysed with direct genomic sequencing of
      15 HNSCC specimens. A novel missense mutation with presumed loss of
      heterozygosity (LOH) and 10 polymorphisms were identified in these samples. The
      novel mutation of STK11/LKB1 at nucleotide position 613 G --> A, which causes the
      amino-acid substitution from alanine to threonine at residue 205 within the
      catalytic kinase domain, was identified in cell line RPMI 2650. To further
      determine whether this point mutation affects the gene function, constructs of
      the wild type and A205T mutant of the STK11/LKB1 gene expression vectors were
      created and transfected into RPMI 2650 cells. Our results showed that the
      reintroduction of the wild-type but not the mutant STK11/LKB1 construct into RPMI
      2650 cells induced suppression of the cell growth. The mutation also affected the
      kinase activity of the Stk11/Lkb1 protein. This led us to conclude that the A205T
      point mutation of the STK11/LKB1 gene produces functionally inactive proteins.
      This is the first described mutation of the STK11/LKB1 gene in HNSCC. While the
      mutation frequency of the STK11/LKB1 gene in HNSCC remains to be determined in
      future studies, our data strongly suggests that STK11/LKB1 is involved in the
      carcinogenesis of HNSCC.

PMID- 16407839
TI  - Stability of p21Waf1/Cip1 CDK inhibitor protein is responsive to RhoA-mediated
      regulation of the actin cytoskeleton.
AB  - The proto-oncogene Ras GTPase stimulates transcription of p21Waf1/Cip1 (p21),
      which is repressed by the RhoA GTPase. We previously showed that Ras also
      elevates p21 protein levels by reducing its proteasome-mediated degradation.
      Therefore, we investigated whether RhoA also influenced p21 protein degradation.
      Pulse-chase analysis of p21 protein stability revealed that inhibitors of Rho
      function, which disrupt filamentous actin (F-actin), drastically slowed p21
      degradation. Direct F-actin disruption mimicked Rho inhibition to stabilize p21.
      We found that Rho inhibition, or F-actin disruption, activated the JNK stress
      activated protein kinase, and that interfering with JNK signalling, but not p38,
      abrogated p21 stabilization by Rho inhibition or F-actin-disrupting drugs. In
      addition, Ras-transformation led to increased constitutive JNK activity that
      contributed to the elevated p21 protein levels. These data suggest that p21
      stability is influenced by a mechanism that monitors F-actin downstream of Rho,
      and which acts through a pathway involving activation of JNK. These results may
      have significant implications for therapies that target Rho-signalling pathways
      to induce p21-mediated cell-cycle arrest.

PMID- 16407838
TI  - Fhit modulation of the Akt-survivin pathway in lung cancer cells: Fhit-tyrosine
      114 (Y114) is essential.
AB  - The Fhit tumor suppressor binds and hydrolyses diadenosine polyphosphates and the
      Fhit-substrate complex has been proposed as a proapoptotic effector, as
      determined by infection of susceptible cancer cells with adenoviruses carrying
      wild-type fragile histidine triad (FHIT) or catalytic site mutants. The highly
      conserved Fhit tyrosine 114 (Y114), within the unstructured loop C-terminal of
      the catalytic site, can be phosphorylated by Src family tyrosine kinases,
      although endogenous phospho-Fhit is rarely detected. To explore the importance of
      Y114 and identify Fhit-mediated signaling events, wild-type and Y114 mutant FHIT
      expressing adenoviruses were introduced into two human lung cancer cell lines.
      Caspase-dependent apoptosis was effectively induced only by wild-type but not
      Y114 mutant Fhit proteins. By expression profiling of FHIT versus mutant FHIT
      infected cells, we found that survivin, an Inhibitor of Apoptosis Protein (IAP)
      family member, was significantly decreased by wild-type Fhit. In addition, Fhit
      inhibited activity of Akt, a key effector in the phosphatidylinositol 3-OH kinase
      (PI3K) pathway; loss of endogenous Fhit expression caused increased Akt activity
      in vitro and in vivo, and overexpression of constitutively active Akt inhibited
      Fhit-induced apoptosis. The results indicate that the Fhit Y114 residue plays a
      critical role in Fhit-induced apoptosis, occurring through inactivation of the
      PI3K-Akt-survivin signal pathway.

PMID- 16407840
TI  - A functional analysis of PCNA-binding peptides derived from protein sequence,
      interaction screening and rational design.
AB  - Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function,
      but functions as a sliding platform to mediate protein interactions with the DNA
      strand. Many proteins interact with PCNA through a small conserved motif with
      consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to
      analyse the function of PCNA-binding peptides. Interacting peptides were
      identified using two-hybrid screening; one (pep102) binds directly to a
      physiologically relevant site on PCNA. The EGFP-pep102 overexpression phenotype
      is consistent with competitive blocking of PCNA-protein interactions. Various
      PCNA-binding peptides were all shown to inhibit PCNA function by competitive
      binding in both human and S. pombe cells as EGFP fusion proteins. The action of a
      p21(WAF1/Cip1)-derived peptide was complicated by the presence of additional
      functional domains and possible post-translational modification. The activity of
      pep102 was hampered by low expression in both model systems. The peptide derived
      from rational design (con1) was stable, highly active in inhibiting PCNA function
      both S. pombe and human cells and showed a high affinity for PCNA both in vitro
      and in vivo. These results validate the use of functional screening in yeast to
      identify peptide aptamers that are functional in mammalian cells; such aptamers
      provide excellent leads for small molecule antiproliferative therapies.

PMID- 16407841
TI  - Regulation of high molecular weight-melanoma associated antigen (HMW-MAA) gene
      expression by promoter DNA methylation in human melanoma cells.
AB  - The human high molecular weight-melanoma associated antigen (HMW-MAA) is a
      membrane-bound chondroitin sulfate proteoglycan that is variably expressed in a
      high percentage of melanoma cell lines and tumors. Since the mechanism(s)
      regulating HMW-MAA expression has(ve) not been defined, in this study, we have
      examined whether promoter DNA methylation regulates the level of HMW-MAA
      expression. In melanoma cell lines, the level of HMW-MAA mRNA and protein
      expression is coordinately regulated, implicating a transcriptional control
      mechanism. Consistent with a role for regulation by DNA methylation, we have
      found that a dense CpG island flanks the human HMW-MAA gene transcriptional start
      site. Methylation-specific PCR and sodium bisulfite DNA sequencing analyses
      indicate that the HMW-MAA promoter is heavily methylated in melanoma cell lines,
      melanoma lesions and normal lymphocytes that do not express HMW-MAA; in contrast,
      the HMW-MAA promoter is not methylated in melanoma cell lines and tumors that
      express this antigen. In addition, HMW-MAA expression is markedly induced in HMW
      MAA-negative melanoma cell lines by incubation with the DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine. In summary, our results establish DNA
      methylation as a key regulator of HMW-MAA expression by human melanoma cells.
      This information represents a useful background to optimize immunotherapeutic
      strategies targeting HMW-MAA.

PMID- 16407842
TI  - P21Cip1/WAF1 downregulation is required for efficient PCNA ubiquitination after
      UV irradiation.
AB  - p21(Cip1/WAF1) is a known inhibitor of the short-gap filling activity of
      proliferating cell nuclear antigen (PCNA) during DNA repair. In agreement, p21
      degradation after UV irradiation promotes PCNA-dependent repair. Recent reports
      have identified ubiquitination of PCNA as a relevant feature for PCNA-dependent
      DNA repair. Here, we show that PCNA ubiquitination in human cells is notably
      augmented after UV irradiation and other genotoxic treatments such as
      hydroxyurea, aphidicolin and methylmethane sulfonate. Intriguingly, those DNA
      damaging agents also promoted downregulation of p21. While ubiquitination of PCNA
      was not affected by deficient nucleotide excision repair (NER) and was observed
      in both proliferating and arrested cells, stable p21 expression caused a
      significant reduction in UV-induced ubiquitinated PCNA. Surprisingly, the
      negative regulation of PCNA ubiquitination by p21 does not depend on the direct
      interaction with PCNA but requires the cyclin dependent kinase binding domain of
      p21. Taken together, our data suggest that p21 downregulation plays a role in
      efficient PCNA ubiquitination after UV irradiation.

PMID- 16407843
TI  - p21CDKN1A allows the repair of replication-mediated DNA double-strand breaks
      induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor
      7-hydroxystaurosporine.
AB  - This study provides evidence for the importance of p21(CDKN1A) for the repair of
      replication-mediated DNA double-strand breaks (DSBs) induced by topoisomerase I.
      We report that defects of p21(CDKN1A) and p53 enhance camptothecin-induced
      histone H2AX phosphorylation (gammaH2AX), a marker for DNA DSBs. In human colon
      carcinoma HCT116 cells with wild-type (wt) p53, gammaH2AX reverses after
      camptothecin removal. By contrast, gammaH2AX increases after camptothecin removal
      in HCT116 cells deficient for p53 (p53-/-) or p21(CDKN1A) (p21-/-) as the cells
      reach the late-S and G2 phases. Since p21-/- cells exhibit similar S-phase arrest
      as wt cells in response to camptothecin and aphidicolin does not abrogate the
      enhanced gammaH2AX formation in p21-/- cells, we conclude that enhanced gammaH2AX
      formation in p21-/- cells is not due to re-replication. The cell cycle checkpoint
      abrogator and Chk1/Chk2 inhibitor 7-hydroxystaurosporine (UCN-01) also increases
      camptothecin-induced gammaH2AX formation and inhibits camptothecin-induced
      p21(CDKN1A) upregulation in HCT116 wt cells. TUNEL (terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP-biotin nick end labeling) assays demonstrate that
      gammaH2AX formation in late S and G2 cells following CPT treatment corresponds to
      DNA breaks. However, these breaks are not related to apoptotic DNA fragmentation.
      We propose that p21(CDKN1A) prevents the collapse of replication forks damaged by
      stabilized topoisomerase I cleavage complexes.

PMID- 16407844
TI  - Erythroid progenitor renewal versus differentiation: genetic evidence for cell
      autonomous, essential functions of EpoR, Stat5 and the GR.
AB  - The balance between hematopoietic progenitor commitment and self-renewal versus
      differentiation is controlled by various transcriptional regulators cooperating
      with cytokine receptors. Disruption of this balance is increasingly recognized as
      important in the development of leukemia, by causing enhanced renewal and
      differentiation arrest. We studied regulation of renewal versus differentiation
      in primary murine erythroid progenitors that require cooperation of
      erythropoietin receptor (EpoR), the receptor tyrosine kinase c-Kit and a
      transcriptional regulator (glucocorticoid receptor; GR) for sustained renewal.
      However, mice defective for GR- (GR(dim/dim)), EpoR- (EpoR(H)) or STAT5ab
      function (Stat5ab(-/-)) show no severe erythropoiesis defects in vivo. Using
      primary erythroblast cultures from these mutants, we present genetic evidence
      that functional GR, EpoR, and Stat5 are essential for erythroblast renewal in
      vitro. Cells from GR(dim/dim), EpoR(H), and Stat5ab(-/-) mice showed enhanced
      differentiation instead of renewal, causing accumulation of mature cells and
      gradual proliferation arrest. Stat5ab was additionally required for Epo-induced
      terminal differentiation: differentiating Stat5ab(-/-) erythroblasts underwent
      apoptosis instead of erythrocyte maturation, due to absent induction of the
      antiapoptotic protein Bcl-X(L). This defect could be fully rescued by exogenous
      Bcl-X(L). These data suggest that signaling molecules driving leukemic
      proliferation may also be essential for prolonged self-renewal of normal
      erythroid progenitors.

PMID- 16407845
TI  - Activation of Akt signaling is sufficient to maintain pluripotency in mouse and
      primate embryonic stem cells.
AB  - Embryonic stem (ES) cells can self-renew indefinitely without losing their
      differentiation ability to any cell types. Phosphoinositide-3 kinase (PI3K)/Akt
      signaling plays a pivotal role in various stem cell systems, including the
      formation of embryonic germ (EG) cells from primordial germ cells and self
      renewal of neural stem cells. Here, we show that myristoylated, active form of
      Akt (myr-Akt) maintained the undifferentiated phenotypes in mouse ES cells
      without the addition of leukemia inhibitory factor (LIF). The effects of myr-Akt
      were reversible, because LIF dependence and pluripotent differentiation activity
      were restored by the deletion of myr-Akt. In addition, myr-Akt-Mer fusion
      protein, whose enzymatic activity is controlled by 4-hydroxy-tamoxifen, also
      maintained the pluripotency of not only mouse but also cynomolgus monkey ES
      cells. These results clearly demonstrate that Akt signaling sufficiently
      maintains pluripotency in mouse and primate ES cells, and support the notion that
      PI3K/Akt signaling axis regulates 'stemness' in a broad spectrum of stem cell
      systems.

PMID- 16407846
TI  - A novel activating function of c-Src and Stat3 on HGF transcription in mammary
      carcinoma cells.
AB  - In the normal breast, hepatocyte growth factor (HGF) is primarily expressed by
      stromal cells, and stimulates in a paracrine manner epithelial cells expressing
      the HGF receptor (Met). In invasive human breast carcinomas, HGF and Met are
      frequently overexpressed, possibly establishing an autocrine HGF/Met loop that
      promotes tumour cell invasion. However, the mechanisms leading to autocrine HGF
      expression in carcinoma cells are not known. We previously demonstrated a
      cooperative effect between c-Src and Stat3 in the activation of HGF transcription
      in mammary carcinoma cells. The present report defines a novel Stat3 consensus
      site at nt -95 in the HGF promoter that is highly conserved in human and mouse,
      and is required for c-Src and Stat3 to activate HGF transcription in breast
      epithelial cells. DNA-protein binding studies demonstrated high affinity binding
      of a Stat3-containing complex to the nt -95 site. Endogenous Stat3 binding to
      this region of the HGF promoter in carcinoma cells expressing HGF was
      demonstrated using a chromatin immunoprecipitation assay. In addition,
      coexpression of Stat3 and activated c-Src caused increased expression of
      endogenous HGF mRNA and protein and marked cell scattering in breast epithelial
      cells. Our results delineate a novel c-Src/Stat3-dependent mechanism that
      regulates HGF promoter activity, and is linked to transformation of mammary
      epithelial cells.

PMID- 16407848
TI  - CXCR4 expression mediates glioma cell invasiveness.
AB  - Glioblastoma multiforme is a highly invasive tumor bearing a dismal prognosis.
      Experimental strategies that focus on the specific biological cues governing the
      invasive capacity of these tumors may hold significant therapeutic promise. In
      this context, we describe the in vitro and in vivo association of the cell
      surface chemokine receptor, CXCR4, with the development of an invasive phenotype
      in malignant glioblastoma. We demonstrate that invasive populations of glioma
      cells overexpress CXCR4 at the message and protein levels, and that this
      expression ranges from 25- to 89-fold higher than that found in noninvasive tumor
      cells. Furthermore, neutralization of CXCR4 significantly impairs the in vitro
      invasive capacity of malignant glial cells. In addition, glioma cells secrete
      CXCL12 and demonstrate robust invasive capacity toward a CXCL12 gradient in
      vitro. These findings underscore the importance of CXCR4 as a potential
      therapeutic target for the treatment of invasive glioblastoma.

PMID- 16407847
TI  - N-(4-hydroxyphenyl)retinamide-induced apoptosis triggered by reactive oxygen
      species is mediated by activation of MAPKs in head and neck squamous carcinoma
      cells.
AB  - N-(4-hydroxyphenyl)retinamide (4HPR), a synthetic retinoid effective in cancer
      chemoprevention and therapy, is thought to act via apoptosis induction resulting
      from increased reactive oxygen species (ROS) generation. As ROS can activate MAP
      kinases and protein kinase C (PKC), we examined the role of such enzymes in 4HPR
      induced apoptosis in HNSCC UMSCC22B cells. 4HPR increased ROS level within 1 h
      and induced activation of caspase 3 and PARP cleavage within 24 h. Activation of
      MKK3/6 and MKK4, JNK, p38 and ERK was detected between 6 and 12 h, increased up
      to 24 h and preceded apoptosis. 4HPR-induced activation of these kinases was
      abrogated by the antioxidants BHA and vitamin C. SP600125, a JNK inhibitor,
      suppressed 4HPR-induced c-Jun phosphorylation, cytochrome c release from
      mitochondria and apoptosis. Suppression of JNK1 and JNK2 using siRNA decreased,
      whereas overexpression of wild type-JNK1 enhanced 4HPR-induced apoptosis.
      PD169316, a p38, inhibitor suppressed phosphorylation of Hsp27 and apoptosis.
      PD98059, an MEK1/2 inhibitor, also suppressed ERK1/2 activation and apoptosis
      induced by 4HPR. Likewise, PKC inhibitor GF109203X suppressed ERK and p38
      phosphorylation and PARP cleavage. These data indicate that 4HPR-induced
      apoptosis is triggered by ROS increase, leading to the activation of the mitogen
      activated protein serine/threonine kinases JNK, p38, PKC and ERK, and subsequent
      apoptosis.

PMID- 16407849
TI  - The carbonic anhydrase I locus contains a c-Myb target promoter and modulates
      differentiation of murine erythroleukemia cells.
AB  - The Myb proto-oncogene encodes a transcription factor (c-Myb) that is essential
      for normal hematopoiesis and is thought to regulate hematopoietic cell
      proliferation and differentiation by regulating expression of specific target
      genes. We identify the mouse erythroid-specific carbonic anhydrase I promoter
      (CAIe) as a target of c-Myb activity and demonstrate that Myb activity is
      critical for carbonic anhydrase I (CAI) expression in C19 MEL cells. CAI
      expression is downregulated when MEL cells differentiate in response to MEnT or
      treatment with N, N-hexamethylene bisacetamide (HMBA). Coexpression of GATA-1
      with c-Myb results in synergistic activation of transcription from the CAIe
      promoter and both transcription factors interact with the CAIe promoter in vivo.
      We identify a novel 20 bp sequence in the CAIe promoter that is sufficient to
      mediate synergistic activation of the CAIe promoter by c-Myb and GATA-1. c-Myb
      and GATA-1 interact with this DNA sequence suggesting that c-Myb and GATA-1 may
      be contained in a complex that interacts with this region of the CAIe promoter.
      Forced expression of CAI delayed HMBA-induced differentiation of MEL cells and
      maintained them in a proliferating state. These data strongly suggest that CAI is
      a c-Myb target and is involved in regulating MEL cell proliferation and
      differentiation.

PMID- 16407850
TI  - Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and
      invasion of head and neck squamous carcinoma cells.
AB  - Squamous cell carcinoma (SCC) cells of the head and neck specifically express
      collagenase-3 (matrix metalloproteinase-13 (MMP-13)), the expression of which
      correlates with their invasion capacity. Transforming growth factor-beta (TGF
      beta) enhances MMP-13 and collagenase-1 (MMP-1) expression and invasion of SCC
      cells via p38 mitogen-activated protein kinase. Here, we have examined the role
      of Smad signaling in regulating MMP-13 expression and in invasion of head and
      neck SCC cells. Treatment with TGF-beta resulted in activation of Smad2 and Smad3
      in SCC cells, but had no effect on their proliferation or viability. Basal
      activation of Smad3 and p38 was noted in SCC cells without exogenous TGF-beta
      stimulation, and adenoviral delivery of Smad7 and dominant-negative Smad3
      inhibited p38 activation in these cells. Adenoviral overexpression of Smad3
      augmented the upregulatory effect of TGF-beta on MMP-13 expression by SCC cells.
      Disruption of Smad signaling by adenoviral expression of kinase-defective TGF
      beta type I receptor (activin-receptor-like kinase-5), Smad7, and dominant
      negative Smad3 potently suppressed the basal and TGF-beta-induced expression of
      MMP-13 and MMP-1 in SCC cells, and inhibited their basal and TGF-beta-induced
      invasion through Matrigel and type I collagen. Adenoviral overexpression of Smad7
      in cutaneous and oral SCC cells significantly inhibited their implantation in
      skin of SCID mice and growth of xenografts in vivo, as compared to LacZ
      adenovirus-transduced control cells. Together, these results show that Smad
      signaling plays an important role in promoting the invasive phenotype of human
      head and neck SCC cells by upregulating their collagenase expression.

PMID- 16407851
TI  - Dysregulated expression of mitotic regulators is associated with B-cell
      lymphomagenesis in HOX11-transgenic mice.
AB  - Dysregulated expression of the homeobox gene, HOX11 is a frequent etiologic event
      in T-cell acute lymphoblastic leukemias. HOX11-transgenic mice (IgHmu-HOX11Tg)
      expressing HOX11 in the B-cell compartment develop B-cell lymphomas with extended
      latency. The latency suggests that additional genetic events are required prior
      to the onset of malignant lymphoma. We report the identification of 17 HOX11
      collaborating genes, revealed through their propensity to be targeted in a
      proviral insertional mutagenesis screen. Seven integrations disrupted genes in
      mitotic spindle checkpoint control, suggesting that cells with elevated HOX11
      expression are especially sensitive to dysregulation of chromosome segregation
      during mitosis. IgHmu-HOX11Tg primary B-lymphocyte cultures exposed to the
      aneugenic agents, colchicine and colcemid, exhibited increased incidences of
      chromosome missegregation as assessed by cytokinesis-block micronucleus assays.
      Additionally, IgHmu-HOX11Tg cultures were shown to exhibit aberrant bypass of
      spindle checkpoint arrest, as assessed by the increased presence of cycling cells
      determined by assessment of DNA content and by BrdU immunolabelling. Western
      immunoblotting revealed elevated expression of the mitotic effector molecules,
      cyclin A, cyclin B1 and cdc20 in IgHmu-HOX11Tg cultures. Moreover, spontaneously
      arising lymphoid neoplasms in IgHmu-HOX11Tg mice frequently exhibit aberrant
      expression of mitotic regulators, concomitant with increased development of
      micronuclei, abnormal mitotic checkpoint control and increased incidences of
      abnormal karyotypes when expanded in culture. Collectively, these findings
      indicate that abnormal regulation of spindle checkpoint control as a result of
      HOX11 overexpression leads to a heightened predisposition for development of
      aneuploidy, contributing to oncogenesis.

PMID- 16407852
TI  - Linking DNA damage to medulloblastoma tumorigenesis in patched heterozygous
      knockout mice.
AB  - Hemizygous Ptc1 mice have many features of Gorlin syndrome, including
      predisposition to medulloblastoma development. Ionizing radiation synergize with
      Ptc1 mutation to induce medulloblastoma only in neonatally exposed mice. To
      explore the mechanisms underlying age-dependent susceptibility, we irradiated
      Ptc(neo67/+) mice at postnatal day 1 (P1) or 10 (P10). We observed a dramatic
      difference in medulloblastoma incidence, which ranged from 81% in the cerebellum
      irradiated at P1 to 3% in the cerebellum irradiated at P10. A striking difference
      was also detected in the frequency of cerebellar preneoplastic lesions (100
      versus 14%). Our data also show significantly lower induction of apoptosis in the
      cerebellum of medulloblastoma-susceptible (P1) compared to -resistant (P10) mice,
      strongly suggesting that medulloblastoma formation in Ptc1 mutants may be
      associated with resistance to radiation-induced cell killing. Furthermore, in
      marked contrast with P10 mice, cerebellum at P1 displays substantially increased
      activation of the cell survival-promoting Akt/Pkb protein, and markedly decreased
      p53 levels in response to radiation-induced genotoxic stress. Overall, these
      results show that developing cerebellar granule neuron precursors' (CGNPs)
      radiosensitivity to radiation-induced cell death increases with progressing
      development and inversely correlates with their ability to neoplastically
      transform.

PMID- 16407853
TI  - Implantation of a new porous gelatin-siloxane hybrid into a brain lesion as a
      potential scaffold for tissue regeneration.
AB  - For brain tissue regeneration, any scaffold for migrated or transplanted stem
      cells with supportive angiogenesis is important once necrotic brain tissue has
      formed a cavity after injury such as cerebral ischemia. In this study, a new
      porous gelatin-siloxane hybrid derived from the integration of gelatin and 3
      (glycidoxypropyl) trimethoxysilane was implanted as a three-dimensional scaffold
      into a defect of the cerebral cortex. The porous hybrid implanted into the lesion
      remained at the same site for 60 days, kept integrity of the brain shape, and
      attached well to the surrounding brain tissues. Marginal cavities of the
      scaffolds were occupied by newly formed tissue in the brain, where newly produced
      vascular endothelial, astroglial, and microglial cells were found with
      bromodeoxyuridine double positivity, and the numbers of those cells were dose
      dependently increased with the addition of basic fibroblast growth factor (bFGF)
      and epidermal growth factor (EGF). Extension of dendrites was also found from the
      surrounding cerebral cortex to the newly formed tissue, especially with the
      addition of bFGF and EGF. The present study showed that a new porous gelatin
      siloxane hybrid had biocompatibility after implantation into a lesion of the
      central nervous system, and thus provided a potential scaffold for cell
      migration, angiogenesis and dendrite elongation with dose-dependent effects of
      additive bFGF and EGF.

PMID- 16407854
TI  - CBF changes associated with focal ischemic preconditioning in the spontaneously
      hypertensive rat.
AB  - Experimental stroke models exhibit robust protection after prior preconditioning
      (PC) insults. This study comprehensively examined cerebral blood flow (CBF)
      responses to permanent middle cerebral artery (MCA) occlusion in spontaneously
      hypertensive rats preconditioned by noninjurious transient focal ischemia, using
      [(14)C]iodoantipyrine autoradiography at varied occlusion intervals.
      Preconditioning was produced by 10-min occlusion of the MCA and ipsilateral
      common carotid artery under halothane anesthesia. These vessels were permanently
      coagulated 24 h later in naive, PC, and sham-operated rats. Infarct volumes were
      determined from hematoxylin-eosin-stained frozen sections after 1 or 3 days.
      Edema-corrected infarct volume was reduced from 127+/-21 in naive rats to 101+/
      31 and 52+/-28 mm(3) in sham and PC groups, respectively, at 1 day, with similar
      results at 3 days. All animals exhibited a consistent CBF threshold for
      infarction (approximately 30 mL/100 g/min). Tissue volumes below this threshold
      were identical in naive and PC groups after 15-min occlusion. However, by 3 h the
      volume of ischemic cortex decreased in the PC group but remained unchanged in
      naive rats, predicting final infarct volumes. Cerebral blood flow recovery was
      confirmed in brains of individual rats evaluated by repeated laser Doppler
      perfusion imaging during the same 3-h interval. Modest sham protection correlated
      with better-maintained global perfusion, detectable also in the contralateral
      cortex, apparently reflecting the PC effects of prior anesthesia. These results
      establish that timely reperfusion of penumbra, achieved by synergistic
      mechanisms, is a primary determinant of PC-induced protection in experimental
      stroke.

PMID- 16407857
TI  - Targets for treatment success.

PMID- 16407855
TI  - Neuronal-glial glucose oxidation and glutamatergic-GABAergic function.
AB  - Prior 13C magnetic resonance spectroscopy (MRS) experiments, which simultaneously
      measured in vivo rates of total glutamate-glutamine cycling (V(cyc(tot))) and
      neuronal glucose oxidation (CMR(glc(ox), N)), revealed a linear relationship
      between these fluxes above isoelectricity, with a slope of approximately 1. In
      vitro glial culture studies examining glutamate uptake indicated that glutamate,
      which is cotransported with Na+, stimulated glial uptake of glucose and release
      of lactate. These in vivo and in vitro results were consolidated into a model:
      recycling of one molecule of neurotransmitter between glia and neurons was
      associated with oxidation of one glucose molecule in neurons; however, the
      glucose was taken up only by glia and all the lactate (pyruvate) generated by
      glial glycolysis was transferred to neurons for oxidation. The model was
      consistent with the 1:1 relationship between DeltaCMR(glc(ox), N) and
      DeltaV(cyc(tot)) measured by 13C MRS. However, the model could not specify the
      energetics of glia and gamma-amino butyric acid (GABA) neurons because
      quantitative values for these pathways were not available. Here, we review recent
      13C and 14C tracer studies that enable us to include these fluxes in a more
      comprehensive model. The revised model shows that glia produce at least 8% of
      total oxidative ATP and GABAergic neurons generate approximately 18% of total
      oxidative ATP in neurons. Neurons produce at least 88% of total oxidative ATP,
      and take up approximately 26% of the total glucose oxidized. Glial lactate
      (pyruvate) still makes the major contribution to neuronal oxidation, but
      approximately 30% less than predicted by the prior model. The relationship
      observed between DeltaCMR(glc(ox), N) and DeltaV(cyc(tot)) is determined by glial
      glycolytic ATP as before. Quantitative aspects of the model, which can be tested
      by experimentation, are discussed.

PMID- 16407858
TI  - Clinical management of BRCA1 and BRCA2 mutation carriers.

PMID- 16407859
TI  - Breast healthcare and cancer control in limited-resource countries: a framework
      for change.

PMID- 16407871
TI  - Trastuzumab adds to adjuvant chemotherapy for resected HER2-positive breast
      cancer.

PMID- 16407872
TI  - Can decompressive surgery improve outcome in patients with metastatic epidural
      spinal-cord compression?

PMID- 16407873
TI  - Is bortezomib superior to high-dose dexamethasone for the treatment of relapsed
      multiple myeloma?

PMID- 16407874
TI  - Are carboplatin and radiotherapy equally effective for the adjuvant treatment of
      stage I seminoma?

PMID- 16407875
TI  - Are EGFR antagonists associated with increased central nervous system metastases
      in non-small-cell lung cancer?

PMID- 16407876
TI  - Does bevacizumab improve survival in patients with metastatic colorectal cancer
      treated with chemotherapy?

PMID- 16407877
TI  - Lessons from phase III clinical trials on anti-VEGF therapy for cancer.
AB  - In randomized phase III trials two anti-vascular endothelial growth factor (VEGF)
      approaches have yielded survival benefit in patients with metastatic cancer. In
      one approach, the addition of bevacizumab, a VEGF-specific antibody, to standard
      chemotherapy improved overall survival in colorectal and lung cancer patients and
      progression-free survival in breast cancer patients. In the second approach,
      multitargeted tyrosine kinase inhibitors that block VEGF receptor and other
      kinases in both endothelial and cancer cells, demonstrated survival benefit in
      gastrointestinal stromal tumor and renal-cell-carcinoma patients. By contrast,
      adding bevacizumab to chemotherapy failed to increase survival in patients with
      previously treated and refractory metastatic breast cancer. Furthermore, addition
      of vatalanib, a kinase inhibitor developed as a VEGF receptor-selective agent, to
      chemotherapy did not show a similar benefit in metastatic colorectal cancer
      patients. These contrasting responses raise critical questions about how these
      agents work and how to combine them optimally. We summarize three of the many
      potential mechanisms of action of anti-VEGF agents, and also discuss progress
      relating to the identification of potential biomarkers for anti-VEGF-agent
      efficacy in humans.

PMID- 16407878
TI  - Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of
      skeletal metastasis.
AB  - The discovery of osteoprotegerin, receptor activator of nuclear factor kappa B
      (RANK) and RANK ligand as critical molecular determinants of osteoclastogenesis
      and regulators of bone resorption, has revolutionized our understanding of the
      processes of normal and pathological bone biology. Altering the relative
      biological availabilities of these molecules has direct consequences for the
      regulation of both bone resorption and bone remodeling. Importantly, recent
      research suggests a pivotal role for these molecules in mediating cancer-induced
      bone destruction. This review summarizes the current evidence of osteoprotegerin,
      RANK ligand and RANK involvement in the pathophysiology of skeletal metastasis,
      and of therapeutic targeting of this process.

PMID- 16407879
TI  - Gefitinib response of erlotinib-refractory lung cancer involving meninges--role
      of EGFR mutation.
AB  - BACKGROUND: A 70-year-old Japanese-American woman who had never smoked was
      diagnosed with stage IV non-small-cell lung cancer with rib metastases. She had
      previously been well and she had no family history of malignancy. While receiving
      treatment with erlotinib, an epidermal growth factor receptor small-molecule
      inhibitor, she progressed and developed new brain metastases. She failed further
      chemotherapy treatments and subsequently developed extensive symptomatic
      leptomeningeal carcinomatosis associated with diplopia, hemiparesis, weight loss,
      and incontinence. INVESTIGATIONS: Chest X-ray, head and chest CT scan, R2 lymph
      node biopsy, histopathology, immunohistochemistry, MRI of head and spine, lumbar
      puncture, laser microdissection and EGFR genomic DNA sequencing of the R2 lymph
      node and cerebrospinal fluid tumor cells. DIAGNOSIS: Erlotinib-refractory stage
      IV lung adenocarcinoma and end-stage symptomatic leptomeningeal metastases with a
      novel double L858R + E884K somatic mutation of the EGFR. MANAGEMENT: Carboplatin,
      paclitaxel and erlotinib, whole-brain radiotherapy, temozolomide with and without
      irinotecan, and gefitinib.

PMID- 16407880
TI  - Pivotal role of xanthine oxidase in the initiation of tubulointerstitial renal
      injury in rats with hyperlipidemia.
AB  - Hyperlipidemia can induce or aggravate renal tubulointerstitial injury.
      Experiments in a complex rat model with chronic glomerulonephritis and long
      standing, coexisting hyperlipidemia suggested that induction of xanthine oxidase
      (XO), with increased oxygen radical generation, is involved in aggravation of
      tubulointerstitial injury. To separate the role of XO in the initial events of
      lipid-mediated tubulointerstitial injury, short-term experiments with diet
      induced hyperlipidemia over 21 and 35 days were performed in otherwise healthy
      rats. XO expression in relation to the antioxidant enzymes was examined in the
      cortical tubulointerstitium (TIS) and proximal tubules (PT). Subsequent
      experiments with XO inhibition were performed, examining tubulointerstitial
      infiltration with ED1-positive cells and expression of adhesion molecules and
      monocyte chemoattractant protein-1 (MCP-1) as indicators of early injurious
      events. Hyperlipidemia increased XO activity in TIS by 40 and 86%, and in PT by
      28 and 90% at days 21 and 35, compared with controls on regular diet. This
      increased activity was associated with increased reactive oxygen species. Among
      the antioxidant enzymes, glutathione peroxidase activity increased in TIS by 40%
      and in PT by 90%. Histological evaluation showed a three-fold increase in ED1
      positive cells and increased MCP-1 and vascular cell adhesion molecule-1 (VCAM-1)
      expression at day 35 in the TIS. Inhibition of XO prevented tubulointerstitial
      ED1 cell infiltration, together with a decreased expression of MCP-1 and VCAM-1.
      These results point to an important role for XO in the early stage of
      hyperlipidemia-associated renal injury, mediating macrophage infiltration by a
      putatively redox-dependent upregulation of MCP-1 and VCAM-1.

PMID- 16407882
TI  - New intrarenal echo-Doppler velocimetric indices for the diagnosis of renal
      artery stenosis.
AB  - We aimed at comparing the positive and negative predictive values (PPV, NPV) of
      several intrarenal velocimetric indices for revealing the presence of renal
      artery stenosis (RAS) among hypertensive patients who underwent a renal
      angiography for the clinical suspicion of renovascular hypertension. In 106
      patients (200 kidneys), the pulsatility index (PI) and resistive index (RI), the
      acceleration time (AT), and the mean systolic acceleration (ACC(sys)) were
      evaluated. In addition, the maximal systolic acceleration (ACC(max)), that is,
      the maximal slope of the acceleration phase, and the maximal acceleration index
      (AI(max)), that is, the ratio between ACC(max) and the relative peak systolic
      velocity, were calculated. On angiography, we found that 56 (28%) of the 200
      arteries had a greater than 60% RAS. PI and RI had an NPV below 75%, whereas AT,
      ACC(sys), ACC(max), and AI(max) had an NPV always above 95%. However, ACC(max),
      and AI(max), at their best cutoff limits, had higher PPV than ACC(sys) and AT (60
      and 70% vs 45 and 51%, respectively). Thus, in a cohort of patients with a high
      prevalence of RAS, PI and RI failed to reach an NPV adequate for a screening
      test. In contrast, all the acceleration indices we tested had a sufficiently high
      NPV but AI(max) appears superior to the others because of higher PPV. We propose
      the evaluation of AI(max) as an additional screening test in patients with
      hypertension and the clinical suspicion of RAS.

PMID- 16407881
TI  - Clinical markers in adult offspring of families with and without Balkan Endemic
      Nephropathy.
AB  - Balkan Endemic Nephropathy (BEN) is a kidney disease that progresses slowly. Only
      a few studies have investigated renal clinical markers in offspring of BEN
      families before the onset of the disease. This project aimed to determine whether
      kidney function and structure are altered in BEN offspring compared with non-BEN
      offspring. The study population consisted of 102 adult BEN offspring and a
      control group of 99 non-BEN offspring. We collected urine and blood samples, and
      conducted face-to-face interviews, physical examinations and ultrasound
      measurements of the kidney. Total protein, albumin, beta2-microglobulin and
      creatinine in urine, creatinine and urea in serum, and creatinine clearance (CCR)
      were determined. Two risk factors were assessed: first, the overall status of
      being an offspring from a BEN family, and second, the specific status of a mother
      and/or father with BEN. The data were analyzed using linear regression. After
      adjusting for confounders, we found that kidney length and minimal cortex width
      in BEN offspring were significantly decreased. Urine concentrations of total
      protein, albumin, and beta2-microglobulin were higher in BEN offspring. Regarding
      parental history, the associations were statistically significant only for the
      offspring of mothers who had BEN, with the exception of minimal cortex width,
      which showed no parental difference. For CCR, we did not identify a statistically
      significant effect for BEN offspring status nor for parental history. In
      conclusion, adult offspring of BEN families can be characterized by shorter
      kidney length and an increased excretion of albumin, total protein, and beta2
      microglobulin, in particular, when the mother had BEN.

PMID- 16407883
TI  - Transmembrane pressure modulation in high-volume mixed hemodiafiltration to
      optimize efficiency and minimize protein loss.
AB  - The aim of the present study was transmembrane pressure (TMP) modulation in high
      volume mixed hemodiafiltration (HDF) to optimize efficiency and minimize protein
      loss. The optimal flow/pressure conditions in on-line mixed HDF assisted with a
      feedback control of TMP were defined in this prospective randomized study in
      order to obtain maximal efficiency in solute removal while minimizing potential
      side effects. Two different TMP profiles in mixed HDF were compared in 12
      unselected patients who underwent two study periods of 2 weeks each in cross-over
      randomized sequence: (A) constant TMP at around 300 mmHg and (B) profiled TMP, in
      which TMP was slowly increased from a low initial value to the maximal value. In
      both procedures, the mean volume exchange was 10.6+/-1.4 l/h. Mean filtration
      fraction was 53%. Instantaneous beta2-microglobulin (beta2-m) clearance was
      higher at the start of the session with profiled TMP (207+/-35 vs 194+/-28
      ml/min, P<0.005), whereas no differences were found at the end (135+/-19 vs 132+/
      19 ml/min). Profiled TMP resulted in a higher mean beta2-m clearance of the
      session (97.0+/-15.4 vs 87.8+/-18.3 ml/min, P<0.01), in lower albumin loss in the
      first 30 min (0.62+/-0.14 vs 0.98+/-0.18 g, P<0.0001), and, in the whole session
      (3.98+/-1.19 vs 5.24+/-0.77 g, P<0.001), in higher dialyzer ultrafiltration
      coefficients and lower resistance indexes. This study showed that the TMP
      feedback modulation in mixed HDF was highly effective in maintaining very high
      ultrafiltration rates and filtration fractions, and minimized potential side
      effects as a result of the improved preservation of membrane permeability and
      more favorable dialyzer pressure regimen.

PMID- 16407884
TI  - Retrospective follow-up of transplantation of kidneys from 'marginal' donors.
AB  - The organ shortage has led to extend the procurement to kidneys from 'marginal'
      donors. As a result, an increasing number of kidneys are discarded, but an
      extended analysis of the validity of the clinical decision to accept or decline a
      marginal graft remains to be determined. We have retrospectively analyzed the
      outcome of 170 kidney transplantations, performed in eight renal transplantation
      centers between 1992 and 1998. Study group included transplantation from donors
      accepted after refusal for poor donor or graft quality by at least two centers.
      Control group included 170 paired recipients from kidneys unanimously accepted by
      all centers. Main causes of kidney refusal included impaired donor hemodynamics
      (28%), abnormal pre-harvesting serum creatinine (22%), advanced age in donors
      (15%), and donor atheroma (14%). The 5-year patient survival (88.2% in the study
      group and 88.9% in controls) and graft survival (70.4% in the study group and
      76.7% in controls, P=0.129) were not significantly different. Delayed graft
      function occurred significantly more often in the study group patients than in
      controls patients (63 vs 32%, P<0.0001). Primary non-functioning kidneys were
      significantly more frequently observed in study patients than in controls (7.7 vs
      1.8%, P=0.01). Mean creatinine clearance was significantly lower in the study
      group patients compared with controls during the post-transplant course. Our
      results suggest that these initially discarded kidneys provide satisfactory
      survival rates despite their impaired early functional recovery and poorer long
      term renal function, and therefore might be considered acceptable for
      transplantation in the context of organ shortage.

PMID- 16407885
TI  - Simvastatin protection against acute immune-mediated glomerulonephritis in mice.
AB  - In addition to cholesterol lowering, 3-hydroxy-3-nethylglutaryl coenzyme A (HMG
      CoA) reductase inhibitors limit inflammatory changes associated with
      atherosclerosis. There is also support for their use as inhibitors of progression
      in chronic renal disease, irrespective of cause. In this study, their capacity to
      limit acute renal inflammation was evaluated. For this purpose, mice were treated
      with Simvastatin either prior to, at the time of, or shortly after induction of
      nephrotoxic nephritis. The severity of disease was determined by evaluation of
      blood urea nitrogen (BUN), proteinuria, and renal histologic changes. The
      reversibility of benefit was evaluated by the administration of mevalonic acid
      along with nephrotoxic serum (NTS) and Simvastatin The severity of the acute
      nephritis, including proteinuria, elevated BUN, and histologic changes, was
      ameliorated in a dose-dependent manner, when Simvastatin was administered either
      prior to NTS injection or at the time of NTS injection. By contrast, Simvastatin
      did not alter the course of established nephritis. Coadministration of mevalonic
      acid, the immediate substrate following HMG-CoA reductase, abolished
      Simvastatin's renoprotective effect, indicating that the benefit is, at least in
      part, due to interference with HMG-CoA reductase and biosynthetic substrates
      downstream from the enzyme. These findings provide the rationale for the
      evaluation of the efficacy of HMG-CoA reductase inhibitors in patients with
      recurrent forms of renal inflammation, to limit the severity of acute
      exacerbations of disease, prevent renal scarring and slow the rate of
      progression.

PMID- 16407886
TI  - Comparative efficacy of renal preservation solutions to limit functional
      impairment after warm ischemic injury.
AB  - In kidney transplantation, cold storage is the dominant modality used to prolong
      organ viability ex vivo, but is inevitably followed by a period of warm ischemia.
      Preservation fluids limit tissue damage during the ischemic period, but there is
      little information on the influence of preservation fluids on the physiologic
      consequences of warm ischemia alone, or on the comparative ability of such
      preservation fluids to limit warm ischemic injury. In this study, warm ischemia
      was induced in rat kidneys by crossclamping the left renal pedicle for 45 min
      with contralateral nephrectomy. The ischemic kidneys were flushed with Euro
      Collins (EC), hyper osmolar citrate (HOC), University of Wisconsin (UW), or
      phosphate buffered sucrose (PBS)140 solution. Over a period of 2 h after
      reperfusion, urine and blood samples were collected and physiological parameters
      related to the function of the postischemic kidneys were assessed. The data show
      that postischemic renal function can be influenced by the choice of preservation
      fluid. Essentially, the continued use of EC as a renal preservation solution
      finds little support in these data, and, while HOC and UW solutions were better
      able to limit the decline in renal function after warm ischemia than EC, the
      solution most able to limit functional impairment after warm ischemia was PBS140.
      This analysis compares the efficacies of the commonly used preservation solutions
      and could form the basis for future solid-organ transplant studies that may
      ultimately allow us to propose best-practice guidelines and an optimum platform
      for improved preservation solutions.

PMID- 16407887
TI  - The impact of home nocturnal hemodialysis on end-stage renal disease therapies: a
      decision analysis.
AB  - Home nocturnal hemodialysis (HNHD) is cost-effective relative to in-center
      hemodialysis (IHD) in short-run analyses. The effect in long-run analyses, when
      technique failures, declining benefits, delayed training, transplantation and
      death are considered, is unknown. We used decision analysis techniques to examine
      the relative cost-effectiveness of HNHD and IHD, projecting future costs and
      health effects over a lifetime with end-stage renal disease. We developed a
      Markov state-transition model comparing two strategies: only IHD or starting on
      IHD and subsequently transferring to HNHD. The model incorporates
      transplantation. In the base case, half the population was eligible for
      transplantation, with (1/3) of grafts from live donors. The time to transplant
      was 0.75 years for live and 5 years for deceased donor transplants. The delay
      before initiation of HNHD was 5 years. Costs and outcomes were discounted at 3%
      per annum. Model parameters were derived from a literature review. We also
      conducted one-way sensitivity analyses and Monte Carlo simulations. The HNHD
      strategy was associated with a quality-adjusted survival estimate of 5.79 quality
      adjusted life years (QALYs), with lifetime costs of $538 094. The values for IHD
      were 5.31 QALYs and $543 602, respectively. Thus, HNHD is cost saving while
      improving quality of life. The incremental cost-utility ratio was consistently
      less than $50 000 per QALY in sensitivity and Monte Carlo analyses. Important
      determinants of cost-effectiveness were transplantation time and whether benefits
      declined over time. Our model suggests that HNHD improves quality-adjusted
      survival over IHD at an economically attractive cost-effectiveness ratio.

PMID- 16407888
TI  - Bacterial RNA and small antiviral compounds activate caspase-1 through
      cryopyrin/Nalp3.
AB  - Missense mutations in the CIAS1 gene cause three autoinflammatory disorders:
      familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset
      multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product
      of CIAS1, is a member of the NOD-LRR protein family that has been linked to the
      activation of intracellular host defence signalling pathways. Cryopyrin forms a
      multi-protein complex termed 'the inflammasome', which contains the apoptosis
      associated speck-like protein (ASC) and caspase-1, and promotes caspase-1
      activation and processing of pro-interleukin (IL)-1beta (ref. 4). Here we show
      the effect of cryopyrin deficiency on inflammasome function and immune responses.
      Cryopyrin and ASC are essential for caspase-1 activation and IL-1beta and IL-18
      production in response to bacterial RNA and the imidazoquinoline compounds R837
      and R848. In contrast, secretion of tumour-necrosis factor-alpha and IL-6, as
      well as activation of NF-kappaB and mitogen-activated protein kinases (MAPKs)
      were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like
      receptors and cryopyrin control the secretion of IL-1beta and IL-18 through
      different intracellular pathways. These results reveal a critical role for
      cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1,
      and provide insights regarding the pathogenesis of autoinflammatory syndromes.

PMID- 16407889
TI  - Gout-associated uric acid crystals activate the NALP3 inflammasome.
AB  - Development of the acute and chronic inflammatory responses known as gout and
      pseudogout are associated with the deposition of monosodium urate (MSU) or
      calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and
      periarticular tissues. Although MSU crystals were first identified as the
      aetiological agent of gout in the eighteenth century and more recently as a
      'danger signal' released from dying cells, little is known about the molecular
      mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU
      and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin)
      inflammasome, resulting in the production of active interleukin (IL)-1beta and IL
      18. Macrophages from mice deficient in various components of the inflammasome
      such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta
      activation. Moreover, an impaired neutrophil influx is found in an in vivo model
      of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient
      in the IL-1beta receptor (IL-1R). These findings provide insight into the
      molecular processes underlying the inflammatory conditions of gout and
      pseudogout, and further support a pivotal role of the inflammasome in several
      autoinflammatory diseases.

PMID- 16407891
TI  - In vivo quantification of ethanol kinetics in rat brain.
AB  - Proton magnetic resonance spectroscopy was used at 3T to measure the uptake and
      clearance of brain ethanol in rats after bolus intraperitoneal (i.p.) or
      intragastric (i.g.) alcohol injection, and to estimate the effects of acute
      alcohol on brain metabolites. The observation duration was 1-1.5 h with temporal
      resolution of alcohol sampling ranging from 4 s-4 min. The observed time course
      of alcohol brain concentration followed a consistent pattern characterized by a
      rapid absorption, an intermediate distribution, and a slower clearance that
      approached a linear decay. In a sample of eight healthy Wistar rats, the
      intercept of the linear clearance term, extrapolated back to the time of
      injection, correlated well with the administered dose per unit of lean body mass.
      Alcohol concentration estimation based on spectroscopically measured clearance
      was compared with blood alcohol levels from blood samples at the end of
      observation, and were in good agreement with the administered dose. Serial proton
      spectroscopy measurements provide a valid in vivo method for quantifying brain
      alcohol uptake and elimination kinetics in real time.

PMID- 16407892
TI  - Anterior cingulate and subgenual prefrontal blood flow changes following
      tryptophan depletion in healthy males.
AB  - In healthy humans, there is an apparent dissociation between cognitive and
      affective consequences of reduced brain serotonin (5-HT), as rapid tryptophan
      depletion (RTD) causes alterations in a consistent constellation of cognitive
      processes in the general absence of mood deterioration. This study aimed to
      investigate possible neural mechanisms underlying this relative dissociation by
      measuring the effects of reduced 5-HT on regional cerebral blood flow (rCBF). A
      total of 16 healthy, euthymic male subjects (mean age 39+/-9 years) without a
      personal or family history of affective disorder had mood ratings and single
      photon emission computed tomography scans with the rCBF tracer 99mTc-HMPAO under
      reduced 5-HT (RTD) and control conditions. Across individuals, modest positive
      and negative changes in subjective happiness associated with RTD were
      significantly correlated with change of rCBF in a cluster comprising subgenual
      (affective) anterior cingulate cortex (ACC) and associated regions (Brodmann's
      area (BA) 25, posterior BA11 and 47, caudate nucleus and ventral striatum; SPM99
      p<0.05, corrected). The covariation was such that increasing sadness was
      associated with increased rCBF and vice versa. Independent of mood change, RTD
      was associated with reduced rCBF in the dorsal (cognitive) ACC (BA32; SPM99
      p<0.05, corrected). The subgenual prefrontal cortex and dorsal ACC are important
      components of the ventral and dorsal neural systems that regulate and integrate
      affective and cognitive functions. The results therefore suggest that the
      dissociation between affective and cognitive consequences of RTD may possibly be
      attributable to differential effects of reduced 5-HT on these neural systems.

PMID- 16407890
TI  - Cryopyrin activates the inflammasome in response to toxins and ATP.
AB  - A crucial part of the innate immune response is the assembly of the inflammasome,
      a cytosolic complex of proteins that activates caspase-1 to process the
      proinflammatory cytokines interleukin (IL)-1beta and IL-18. The adaptor protein
      ASC is essential for inflammasome function, binding directly to caspase-1 (refs
      3, 4), but the triggers of this interaction are less clear. ASC also interacts
      with the adaptor cryopyrin (also known as NALP3 or CIAS1). Activating mutations
      in cryopyrin are associated with familial cold autoinflammatory syndrome, Muckle
      Wells syndrome and neonatal onset multisystem inflammatory disease, diseases that
      are characterized by excessive production of IL-1beta. Here we show that
      cryopyrin-deficient macrophages cannot activate caspase-1 in response to Toll
      like receptor agonists plus ATP, the latter activating the P2X7 receptor to
      decrease intracellular K+ levels. The release of IL-1beta in response to
      nigericin, a potassium ionophore, and maitotoxin, a potent marine toxin, was also
      found to be dependent on cryopyrin. In contrast to Asc-/- macrophages, cells
      deficient in the gene encoding cryopyrin (Cias1-/-) activated caspase-1 and
      secreted normal levels of IL-1beta and IL-18 when infected with Gram-negative
      Salmonella typhimurium or Francisella tularensis. Macrophages exposed to Gram
      positive Staphylococcus aureus or Listeria monocytogenes, however, required both
      ASC and cryopyrin to activate caspase-1 and secrete IL-1beta. Therefore,
      cryopyrin is essential for inflammasome activation in response to signalling
      pathways triggered specifically by ATP, nigericin, maitotoxin, S. aureus or L.
      monocytogenes.

PMID- 16407893
TI  - Prenatal exposure to betamethasone decreases anxiety in developing rats:
      hippocampal neuropeptide y as a target molecule.
AB  - Repeated antenatal administration of betamethasone is frequently used as a life
      saving treatment in obstetrics. However, limited information is available about
      the outcome of this therapy in children. The initial prospective studies indicate
      that there are behavioral impairments in children exposed to repeated courses of
      prenatal betamethasone during the third trimester of pregnancy. In this study,
      pregnant rats received two betamethasone injections on day 15 of gestation. Using
      immunohistochemistry, the expression of a powerful anxiolytic molecule
      neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus
      and basolateral amygdala (structures related to anxiety and fear) of the
      offspring. Prenatal betamethasone exposure induced significant increases in NPY
      expression in the hippocampus but not in the amygdala. Indeed, behavioral tests
      in the offspring, between PN20 and PN22 in the open field, on the horizontal bar,
      and in the elevated plus maze, indicated decreases in anxiety, without
      impairments in motor performance or total activity. Decreased body weight in
      betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure.
      Thus, prenatal betamethasone treatment consistently increases hippocampal NPY,
      with decreases in anxiety-related behaviors and hippocampal role in anxiety in
      rats. Animal models may assist in differentiation between pathways of the desired
      main effect of the antenatal corticosteroid treatment and pathways of unwanted
      side effects. This differentiation can lead to specific therapeutic interventions
      directed against the side effects without eliminating the beneficial main effect
      of the corticosteroid treatment.

PMID- 16407894
TI  - Knockout of ERK1 enhances cocaine-evoked immediate early gene expression and
      behavioral plasticity.
AB  - The ability of cocaine to produce lasting neural adaptations in mesocorticolimbic
      brain regions is thought to promote drug seeking and facilitate addiction in
      humans. The Ras-controlled Raf-MEK-ERK protein kinase signaling cascade has been
      implicated in the behavioral and neurobiological actions of cocaine in animals.
      However, these pharmacological studies have not been able to determine the
      specific role of the two predominant isoforms of ERK (ERK1 and ERK2) in these
      processes. We report here that deletion of the ERK1 isoform, which leads to
      increased ERK2 stimulus-dependent signaling, facilitates the development of
      cocaine-induced psychomotor sensitization and the acquisition of a cocaine
      conditioned place preference. Conversely, pharmacological blockade of ERK
      signaling attenuates the development of psychomotor sensitization to cocaine.
      Finally, cocaine-evoked gene expression in mesocorticolimbic brain regions is
      potentiated in ERK1-deficient mice. Thus, alterations in ERK signaling influence
      both the neurobiological impact of cocaine and its ability to produce enduring
      forms of drug experience-dependent behavioral plasticity. Our results suggest
      that enhanced ERK2 signaling following repeated drug exposure may facilitate the
      development of forms of cocaine-induced plasticity that contribute to addiction.

PMID- 16407895
TI  - Relationship between cortisol responses to stress and personality.
AB  - Although there is growing evidence of links between the cortisol stress response
      and personality, the nature of the relationships and the underlying mechanisms
      require further clarification. The purpose of this study was to examine
      associations between personality traits and cortisol responses to stress using
      the Revised NEO Personality Inventory five-factor model of personality. In total,
      68 healthy adults, aged 18-30 years, completed the personality assessment and
      underwent a laboratory psychological stress test that consisted of a 5 min speech
      and 5-min of mental arithmetic. Findings showed that in the sample as a whole,
      less Openness was associated with lower cortisol responses to the challenge.
      Cortisol responses also corresponded to certain personality dimensions in a
      gender-specific manner. Blunted cortisol responses were associated with higher
      Neuroticism in women and with lower Extraversion in men. These findings suggest
      that personality traits that have been traditionally associated with greater
      psychopathology were also associated with blunted HPA axis responses to stress.

PMID- 16407896
TI  - Intrafamilial correspondences on platelet [3H-]paroxetine-binding indices in
      bulimic probands and their unaffected first-degree relatives.
AB  - Reduced brain serotonin (5-hydroxytryptamine: 5-HT) transporter activity has been
      associated with susceptibility to various forms of psychopathology, including
      bulimia nervosa (BN) and related syndromes characterized by appetitive or
      behavioural dysregulation. We applied density (Bmax) of platelet [3H-]paroxetine
      binding as a proxy for central 5-HT reuptake activity in two groups of women (33
      with BN-spectrum disorders and 19 with no apparent eating or psychiatric
      disorders), most of these individuals' mothers (31 and 18, respectively), and a
      small sampling of their sisters (seven and eight, respectively). Hierarchical
      linear modeling techniques were used to account for nesting of individuals within
      families and diagnostic groupings. Bulimic probands, their mothers, and their
      sisters all displayed significantly lower density (Bmax) of platelet-paroxetine
      binding than did 'control' probands, mothers, or sisters-even when relatives
      showing apparent eating or psychiatric disturbances were excluded. In addition,
      in bulimic probands and mothers, significant within-family correlations were
      obtained on Bmax. These findings imply a heritable trait (or endophenotype),
      linked to 5-HT activity, and carried by BN sufferers and their first-degree
      relatives (even when asymptomatic). We propose that, under conducive
      circumstances, such a trait may increase risk of binge-eating behavior, or
      associated symptoms of affective or behavioral dysregulation.

PMID- 16407897
TI  - Effects of a alpha 2C-adrenoreceptor gene polymorphism on neural responses to
      facial expressions in depression.
AB  - Alterations in processing of emotionally salient information have been reported
      in individuals with major depressive disorder (MDD). Evidence suggests a role for
      noradrenaline in the regulation of a cortico-limbic-striatal circuit that has
      also been implicated in the pathophysiology of MDD. Herein, we studied the
      physiological consequences of a common coding polymorphism of the gene for the
      alpha(2C)-adrenoreceptor (AR) subtype--the deletion of four consecutive amino
      acids at codons 322-325 of the alpha2C-AR (alpha2CDel322-325-AR) in medication
      free, remitted individuals with MDD (rMDD), and healthy control subjects. After
      injection of 10 mCi of H2(15)O, positron emission tomography (PET) measures of
      neural activity were acquired while subjects were viewing unmasked sad, happy,
      and fearful faces. The neural responses to sad facial expressions were increased
      in the amygdala and decreased in the left ventral striatum in rMDD patients
      relative to healthy control subjects. Furthermore, we report that rMDD carriers
      of one or two copies of the alpha2CDel322-325-AR exhibit greater amygdala as well
      as pregenual and subgenual anterior cingulate gyrus neuronal activity in response
      to sad faces than healthy alpha2CDel322-325-AR carriers and rMDD noncarriers.
      These results suggest that the alpha2CDel322-325-AR confers a change in brain
      function implicating this alpha2-AR subtype into the pathophysiology of MDD.

PMID- 16407898
TI  - Norepinephrine transporter blockade can normalize the prepulse inhibition
      deficits found in dopamine transporter knockout mice.
AB  - Dopamine transporter knockout (DAT KO) mice display deficits in sensorimotor
      gating that are manifested by reduced prepulse inhibition (PPI) of the acoustic
      startle reflex. Since PPI deficits may model some of the cognitive dysfunctions
      identified in certain neuropsychiatric patients, we have studied the effects of
      transporter blockers on PPI in wild-type and DAT KO mice. Treatments with High
      dose psychostimulants that block DAT as well as the norepinephrine (NET) and
      serotonin (SERT) transporters (60 mg/kg cocaine or methylphenidate) significantly
      impaired PPI in wild-type mice. By contrast, these treatments significantly
      ameliorated the PPI deficits observed in untreated DAT KO mice. In studies with
      more selective transport inhibitors, the selective NET inhibitor nisoxetine (10
      or 30 mg/kg) also significantly reversed PPI deficits in DAT KO mice. By
      contrast, while the SERT inhibitor fluoxetine (30 mg/kg) normalized these PPI
      deficits in DAT KO mice, citalopram (30 or 100 mg/kg) failed to do so. The
      'paradoxical' effects of cocaine and methylphenidate in DAT KO mice are thus
      likely to be mediated, at least in part by the ability of these drugs to block
      NET, although serotonin systems may also have some role. Together with recent
      microdialysis data, these results support the hypothesis that prefrontal cortical
      NET blockade and consequent enhancement of prefrontal cortical extracellular
      dopamine mediates the reversal of PPI deficits in DAT KO mice.

PMID- 16407899
TI  - Direct evidence of astrocytic modulation in the development of rewarding effects
      induced by drugs of abuse.
AB  - Long-term exposure to pyschostimulants and opioids induced neuronal plasticity.
      Accumulating evidence suggests that astrocytes actively participate in synaptic
      plasticity. We show here that a glial modulator propentofylline (PPF)
      dramatically diminished the activation of astrocytes induced by drugs of abuse,
      such as methamphetamine (METH) and morphine (MRP). In vivo treatment with PPF
      also suppressed both METH- and MRP-induced rewarding effects. On the other hand,
      intra-nucleus accumbens (N.Acc.) administration of astrocyte-conditioned medium
      (ACM) aggravated the development of rewarding effects induced by METH and MRP via
      the Janus kinase/signal transducers and activators of transcription (Jak/STAT)
      pathway, which modulates astrogliosis and/or astrogliogenesis. Furthermore, ACM,
      but not METH itself, clearly induced the differentiation of multipotent neuronal
      stem cells into glial fibrillary acidic protein-positive astrocytes, and this
      effect was reversed by cotreatment with the Jak/STAT inhibitor AG490. Intra
      cingulate cortex (CG) administration of ACM also enhanced the rewarding effect
      induced by METH and MRP. In contrast to ACM, intra-N.Acc. administration of
      microglia-conditioned medium failed to affect the rewarding effects of METH and
      MRP in mice. These findings suggest that astrocyte-, but not microglia-, related
      soluble factors could amplify the development of rewarding effect of METH and MRP
      in the N.Acc. and CG. The present study provides direct evidence that astrocytes
      may, at least in part, contribute to the synaptic plasticity induced by drugs of
      abuse during the development of rewarding effects induced by psychostimulants and
      opioids.

PMID- 16407900
TI  - DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in healthy
      individuals.
AB  - DTNBP1 (dysbindin) is one of the several putative schizophrenia genes supported
      by association, neuroanatomical, and cellular studies. These suggest an
      involvement of DTNBP1 in the prefrontal cortex and cognitive functions mediated
      by interaction with neurotransmitter systems, in particular glutamate. The
      influence of DTNBP1 gene variation on prefrontal brain function at the systemic
      neurophysiological level, though, has not been characterized. The NoGo
      anteriorization (NGA) as an event-related potential (ERP) measure elicited during
      the continuous performance test (CPT) has been established as a valid
      neurophysiological parameter for prefrontal brain function in healthy individuals
      and patients with schizophrenias. In the present study, we therefore investigated
      the influence of eight dysbindin gene variants on the NGA as a marker of
      prefrontal brain function in 48 healthy individuals. Two DTNBP1 polymorphisms
      previously linked to schizophrenia (P1765 and P1320) were found associated with
      changes in the NGA. Post hoc analysis showing an influence of genetic variation
      at these loci on the Go centroid and frontal amplitudes suggest that this might
      be due to modification of the execution of motor processes by the prefrontal
      cortex. This is the first report on a role of DTNBP1 gene variation for
      prefrontal brain function at a systemic neurophysiological level in healthy
      humans. Future studies will have to address the relevance of this observation for
      patients with schizophrenias.

PMID- 16407901
TI  - Chronic olanzapine treatment causes differential expression of genes in frontal
      cortex of rats as revealed by DNA microarray technique.
AB  - Recent emerging biochemical data indicate that several important neuroregulatory
      genes and proteins may be involved in the etiology of schizophrenia and bipolar
      disorder. Additionally, the same genes appear to be targets of several
      psychotropic medications that are used to treat these disorders. Recent DNA
      microarray studies show that genes involved in synaptic neurotransmission, signal
      transduction, and glutamate/GABA regulation may be differentially regulated in
      brains of subjects with schizophrenia. We hypothesized that chronic
      administration of olanzapine to rats would alter expression of various genes that
      may be involved in the etiology of schizophrenia and mood disorders. Rats were
      administered olanzapine (N=20, 2 mg/kg/day) or sterile saline intraperitoneally
      (N=20) daily for 21 days. Control and olanzapine-treated frontal cortices were
      analyzed using cDNA microarray technology. The results showed significant
      downregulation of 31 genes and upregulation of 38 genes by greater than two-fold
      in the drug-treated brains vs controls. Our results provide evidence for altered
      regulation of genes involved with signal transduction and cell communication,
      metabolism and energy pathways, transport, immune response, nucleic acid
      metabolism, and neuronal growth factors. Real-time quantitative RT-PCR analysis
      verified the direction and magnitude of change in six genes of interest:
      calbindin 3, homer 1, regulator of G-protein signaling (RGS) 2, pyruvate kinase,
      Reelin and insulin 2. Western blotting showed significant upregulation in protein
      products for Reelin 410 and Reelin 180 kDa and downregulation for NMDA3B and
      RGS2. Our results show for the first time that olanzapine causes changes in
      levels of several important genes that may be involved in the etiology and
      treatment of schizophrenia and other psychiatric disorders.

PMID- 16407902
TI  - Activation of adenosine A1 receptors reduces anxiety-like behavior during acute
      ethanol withdrawal (hangover) in mice.
AB  - Elevated signs of anxiety are observed in both humans and rodents during
      withdrawal from chronic as well as acute ethanol exposure, and it represents an
      important motivational factor for ethanol relapse. Several reports have suggested
      the involvement of brain adenosine receptors in different actions produced by
      ethanol such as motor incoordination and hypnotic effects. In addition, we have
      recently demonstrated that adenosine A1 receptors modulate the anxiolytic-like
      effect induced by ethanol in mice. In the present study, we evaluated the
      potential of adenosine A1 and A2A receptor agonists in reducing the anxiety-like
      behavior during acute ethanol withdrawal (hangover) in mice. Animals received a
      single intraperitoneal administration of saline or ethanol (4 g/kg) and were
      tested in the elevated plus maze after an interval of 0.5-24 h. The results
      indicated that hangover-induced anxiety was most pronounced between 12 and 18 h
      after ethanol administration, as indicated by a significant reduction in the
      exploration of the open arms of the maze. At this time interval, ethanol was
      completely cleared. The acute administration of 'nonanxiolytic' doses of
      adenosine and the selective adenosine A1 receptor agonist 2-chloro-N6
      cyclopentyladenosine (CCPA), but not the adenosine A2A receptor agonist N6-[2
      (3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), at the onset of
      peak withdrawal (18 h), reduced this anxiogenic-like response. In addition, the
      effect of CCPA on the anxiety-like behavior of ethanol hangover was reversed by
      pretreatment with the selective adenosine A1 receptor antagonist 8-cyclopentyl
      1,3-dipropylxanthine (DPCPX). These results reinforce the notion of the
      involvement of adenosine receptors in the anxiety-like responses and indicate the
      potential of adenosine A1 receptor agonists to reduce the anxiogenic effects
      during ethanol withdrawal.

PMID- 16407903
TI  - Effects of baclofen on cocaine self-administration: opioid- and nonopioid
      dependent volunteers.
AB  - Preclinical and clinical studies suggest that GABAB receptor agonists selectively
      decrease cocaine use. The behavioral mechanism for the interaction between
      baclofen and cocaine in humans is not known, nor have its effects been
      characterized in individuals dependent on both cocaine and methadone. The
      objective of this study is to determine how maintenance on baclofen influences
      smoked cocaine's reinforcing and subjective effects, mood and cocaine craving
      prior to and after the initiation of cocaine use in cocaine-dependent volunteers
      with and without concurrent opioid dependence. Nontreatment-seeking volunteers
      (10 nonopioid dependent; seven methadone maintained), residing on an in-patient
      research unit for 21 days, were maintained on each baclofen dose (0, 30, 60 mg
      po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was
      determined twice: on days 3-4 and days 6-7 of each baclofen maintenance
      condition. Cocaine sessions began with a sample trial, when participants smoked
      the cocaine dose available that session, and five choice trials, when
      participants chose between smoking the available cocaine dose or receiving one 5
      dollars merchandise voucher. The results show that in the nonmethadone group,
      baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In
      the methadone group, baclofen decreased craving for cocaine. In both groups,
      baclofen decreased cocaine's effects on heart rate. Baclofen did not alter
      cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group.
      The results from this laboratory study appear consistent with clinical evidence
      showing that baclofen decreases cocaine use in nonopioid-dependent patients
      seeking treatment for cocaine dependence. The distinct pattern of effects in
      methadone-maintained participants suggests baclofen may not be effective in
      opioid-dependent cocaine users.

PMID- 16407904
TI  - Disruption of prepulse inhibition after stimulation of central but not peripheral
      alpha-1 adrenergic receptors.
AB  - Prepulse inhibition (PPI) refers to the attenuation of startle when a weak
      prestimulus precedes the startling stimulus. PPI is deficient in several
      psychiatric illnesses involving poor sensorimotor gating. Previous studies
      indicate that alpha1 adrenergic receptors regulate PPI, yet the extent to which
      these effects are mediated by central vs peripheral receptors is unclear. The
      present studies compared the effects of intracerebroventricular (ICV) vs
      intraperitoneal (IP) delivery of several alpha1 receptor agonists on PPI. Male
      Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 microg/5 microl),
      methoxamine (0, 30, 100 microg/5 microl), or phenylephrine (0, 3, 10, 30 microg/5
      microl) ICV immediately before testing. Separate groups received either
      cirazoline (0, 0.25, 0.50, 0.75 mg/kg), methoxamine (0, 2, 5, 10 mg/kg), or
      phenylephrine (0, 0.1, 2.0 mg/kg) IP 5 min before testing. PPI, baseline startle
      responses, and piloerection, an index of autonomic arousal, were measured.
      Cirazoline disrupted PPI; effective ICV doses were approximately six times lower
      than effective IP doses. Methoxamine disrupted PPI after ICV infusion but failed
      to affect PPI with IP doses that were up to 30-fold higher than the effective ICV
      dose. Phenylephrine disrupted PPI with ICV administration, but did not alter PPI
      after IP injection of even a 20-fold higher dose. None of the ICV treatments
      altered baseline startle magnitude, but phenylephrine and methoxamine lowered
      startle after administration of high systemic doses. Piloerection was induced by
      cirazoline via either route of administration, and by IP methoxamine and
      phenylephrine, but not by ICV infusion of methoxamine or phenylephrine. These
      findings indicate that alpha1 receptor-mediated PPI disruption occurs exclusively
      through stimulation of central receptors and is dissociable from alterations in
      baseline startle or autonomic effects.

PMID- 16407905
TI  - Effects of tryptophan depletion on the performance of an iterated Prisoner's
      Dilemma game in healthy adults.
AB  - Adaptive social behavior often necessitates choosing to cooperate with others for
      long-term gains at the expense of noncooperative behaviors giving larger
      immediate gains. Although little is know about the neural substrates that support
      cooperative over noncooperative behaviors, recent research has shown that
      mutually cooperative behavior in the context of a mixed-motive game, the
      Prisoner's Dilemma (PD), is associated with increased neural activity within
      reinforcement circuitry. Other research attests to a role for serotonin in the
      modulation of social behavior and in reward processing. In this study, we used a
      within-subject, crossover, double-blind design to investigate performance of an
      iterated, sequential PD game for monetary reward by healthy human adult
      participants following ingestion of an amino-acid drink that either did (T+) or
      did not (T-) contain l-tryptophan. Tryptophan depletion produced significant
      reductions in the level of cooperation shown by participants when playing the
      game on the first, but not the second, study days. This effect was accompanied by
      a significantly diminished probability of cooperative responding given previous
      mutually cooperative behavior. These data suggest that serotonin plays a
      significant role in the acquisition of socially cooperative behavior in human
      adult participants, and suggest novel hypotheses concerning the serotonergic
      modulation of reward information in socially cooperative behavior in both health
      and psychiatric illness.

PMID- 16407906
TI  - A single amino acid governs enhanced activity of DinB DNA polymerases on damaged
      templates.
AB  - Translesion synthesis (TLS) by Y-family DNA polymerases is a chief mechanism of
      DNA damage tolerance. Such TLS can be accurate or error-prone, as it is for
      bypass of a cyclobutane pyrimidine dimer by DNA polymerase eta (XP-V or Rad30) or
      bypass of a (6-4) TT photoproduct by DNA polymerase V (UmuD'2C), respectively.
      Although DinB is the only Y-family DNA polymerase conserved among all domains of
      life, the biological rationale for this striking conservation has remained
      enigmatic. Here we report that the Escherichia coli dinB gene is required for
      resistance to some DNA-damaging agents that form adducts at the N2-position of
      deoxyguanosine (dG). We show that DinB (DNA polymerase IV) catalyses accurate TLS
      over one such N2-dG adduct (N2-furfuryl-dG), and that DinB and its mammalian
      orthologue, DNA polymerase kappa, insert deoxycytidine (dC) opposite N2-furfuryl
      dG with 10-15-fold greater catalytic proficiency than opposite undamaged dG. We
      also show that mutating a single amino acid, the 'steric gate' residue of DinB
      (Phe13 --> Val) and that of its archaeal homologue Dbh (Phe12 --> Ala), separates
      the abilities of these enzymes to perform TLS over N2-dG adducts from their
      abilities to replicate an undamaged template. We propose that DinB and its
      orthologues are specialized to catalyse relatively accurate TLS over some N2-dG
      adducts that are ubiquitous in nature, that lesion bypass occurs more efficiently
      than synthesis on undamaged DNA, and that this specificity may be achieved at
      least in part through a lesion-induced conformational change.

PMID- 16407910
TI  - Ethics and fraud.

PMID- 16407911
TI  - Three cheers for peers.

PMID- 16407913
TI  - French research chief quits over reforms.

PMID- 16407914
TI  - Verdict: Hwang's human stem cells were all fakes.

PMID- 16407915
TI  - Yes, but will it jump?

PMID- 16407916
TI  - DNA tests put death penalty under fire.

PMID- 16407918
TI  - Bird lovers keep sharp eye on owls.

PMID- 16407919
TI  - Methane finding baffles scientists.

PMID- 16407922
TI  - Origins of DNA: base invaders.

PMID- 16407923
TI  - Space exploration: a shot in the dark?

PMID- 16407924
TI  - Prion disease: the shape of things to come.

PMID- 16407925
TI  - All systems go.

PMID- 16407928
TI  - Why should child care be seen as a women's issue?

PMID- 16407929
TI  - Animal-rights extremists lose public support.

PMID- 16407930
TI  - Testing is necessary on animals as well as in vitro.

PMID- 16407931
TI  - Neuroscience gears up for duel on the issue of brain versus deity.

PMID- 16407936
TI  - Extinctions: a message from the frogs.

PMID- 16407937
TI  - Space physics: breaking through the lines.

PMID- 16407940
TI  - Global change: a green source of surprise.

PMID- 16407941
TI  - Behaviour: smells, brains and hormones.

PMID- 16407942
TI  - Lawrence C. Katz (1956-2005).

PMID- 16407938
TI  - Medicine: politic stem cells.

PMID- 16407943
TI  - Teaching in tandem-running ants.
AB  - The ant Temnothorax albipennis uses a technique known as tandem running to lead
      another ant from the nest to food--with signals between the two ants controlling
      both the speed and course of the run. Here we analyse the results of this
      communication and show that tandem running is an example of teaching, to our
      knowledge the first in a non-human animal, that involves bidirectional feedback
      between teacher and pupil. This behaviour indicates that it could be the value of
      information, rather than the constraint of brain size, that has influenced the
      evolution of teaching.

PMID- 16407944
TI  - Hit-and-run planetary collisions.
AB  - Terrestrial planet formation is believed to have concluded in our Solar System
      with about 10 million to 100 million years of giant impacts, where hundreds of
      Moon- to Mars-sized planetary embryos acquired random velocities through
      gravitational encounters and resonances with one another and with Jupiter. This
      led to planet-crossing orbits and collisions that produced the four terrestrial
      planets, the Moon and asteroids. But here we show that colliding planets do not
      simply merge, as is commonly assumed. In many cases, the smaller planet escapes
      from the collision highly deformed, spun up, depressurized from equilibrium,
      stripped of its outer layers, and sometimes pulled apart into a chain of diverse
      objects. Remnants of these 'hit-and-run' collisions are predicted to be common
      among remnant planet-forming populations, and thus to be relevant to asteroid
      formation and meteorite petrogenesis.

PMID- 16407945
TI  - Widespread amphibian extinctions from epidemic disease driven by global warming.
AB  - As the Earth warms, many species are likely to disappear, often because of
      changing disease dynamics. Here we show that a recent mass extinction associated
      with pathogen outbreaks is tied to global warming. Seventeen years ago, in the
      mountains of Costa Rica, the Monteverde harlequin frog (Atelopus sp.) vanished
      along with the golden toad (Bufo periglenes). An estimated 67% of the 110 or so
      species of Atelopus, which are endemic to the American tropics, have met the same
      fate, and a pathogenic chytrid fungus (Batrachochytrium dendrobatidis) is
      implicated. Analysing the timing of losses in relation to changes in sea surface
      and air temperatures, we conclude with 'very high confidence' (> 99%, following
      the Intergovernmental Panel on Climate Change, IPCC) that large-scale warming is
      a key factor in the disappearances. We propose that temperatures at many highland
      localities are shifting towards the growth optimum of Batrachochytrium, thus
      encouraging outbreaks. With climate change promoting infectious disease and
      eroding biodiversity, the urgency of reducing greenhouse-gas concentrations is
      now undeniable.

PMID- 16407947
TI  - A semiconductor source of triggered entangled photon pairs.
AB  - Entangled photon pairs are an important resource in quantum optics, and are
      essential for quantum information applications such as quantum key distribution
      and controlled quantum logic operations. The radiative decay of biexcitons-that
      is, states consisting of two bound electron-hole pairs-in a quantum dot has been
      proposed as a source of triggered polarization-entangled photon pairs. To date,
      however, experiments have indicated that a splitting of the intermediate exciton
      energy yields only classically correlated emission. Here we demonstrate triggered
      photon pair emission from single quantum dots suggestive of polarization
      entanglement. We achieve this by tuning the splitting to zero, through either
      application of an in-plane magnetic field or careful control of growth
      conditions. Entangled photon pairs generated 'on demand' have significant
      fundamental advantages over other schemes, which can suffer from multiple pair
      emission, or require post-selection techniques or the use of photon-number
      discriminating detectors. Furthermore, control over the pair generation time is
      essential for scaling many quantum information schemes beyond a few gates. Our
      results suggest that a triggered entangled photon pair source could be
      implemented by a simple semiconductor light-emitting diode.

PMID- 16407946
TI  - A magnetic reconnection X-line extending more than 390 Earth radii in the solar
      wind.
AB  - Magnetic reconnection in a current sheet converts magnetic energy into particle
      energy, a process that is important in many laboratory, space and astrophysical
      contexts. It is not known at present whether reconnection is fundamentally a
      process that can occur over an extended region in space or whether it is patchy
      and unpredictable in nature. Frequent reports of small-scale flux ropes and flow
      channels associated with reconnection in the Earth's magnetosphere raise the
      possibility that reconnection is intrinsically patchy, with each reconnection X
      line (the line along which oppositely directed magnetic field lines reconnect)
      extending at most a few Earth radii (R(E)), even though the associated current
      sheets span many tens or hundreds of R(E). Here we report three-spacecraft
      observations of accelerated flow associated with reconnection in a current sheet
      embedded in the solar wind flow, where the reconnection X-line extended at least
      390R(E) (or 2.5 x 10(6) km). Observations of this and 27 similar events imply
      that reconnection is fundamentally a large-scale process. Patchy reconnection
      observed in the Earth's magnetosphere is therefore likely to be a geophysical
      effect associated with fluctuating boundary conditions, rather than a fundamental
      property of reconnection. Our observations also reveal, surprisingly, that
      reconnection can operate in a quasi-steady-state manner even when undriven by the
      external flow.

PMID- 16407948
TI  - Ultrafast superheating and melting of bulk ice.
AB  - The superheating of a solid to a temperature beyond its melting point, without
      the solid actually melting, is a well-known phenomenon. It occurs with many
      substances, particularly those that can readily be produced as high-quality
      crystals. In principle, ice should also be amenable to superheating. But the
      complex three-dimensional network of hydrogen bonds that holds water molecules
      together and gives rise to unusual solid and liquid properties strongly affects
      the melting behaviour of ice; in particular, ice usually contains many defects
      owing to the directionality of its hydrogen bonds. However, simulations are
      readily able to 'create' defect-free ice that can be superheated. Here we show
      that by exciting the OH stretching mode of water, it is possible to superheat
      ice. When using an ice sample at an initial temperature of 270 K, we observe an
      average temperature rise of 20 +/- 2 K that persists over the monitored time
      interval of 250 ps without melting.

PMID- 16407949
TI  - Methane emissions from terrestrial plants under aerobic conditions.
AB  - Methane is an important greenhouse gas and its atmospheric concentration has
      almost tripled since pre-industrial times. It plays a central role in atmospheric
      oxidation chemistry and affects stratospheric ozone and water vapour levels. Most
      of the methane from natural sources in Earth's atmosphere is thought to originate
      from biological processes in anoxic environments. Here we demonstrate using
      stable carbon isotopes that methane is readily formed in situ in terrestrial
      plants under oxic conditions by a hitherto unrecognized process. Significant
      methane emissions from both intact plants and detached leaves were observed
      during incubation experiments in the laboratory and in the field. If our
      measurements are typical for short-lived biomass and scaled on a global basis, we
      estimate a methane source strength of 62-236 Tg yr(-1) for living plants and 1-7
      Tg yr(-1) for plant litter (1 Tg = 10(12) g). We suggest that this newly
      identified source may have important implications for the global methane budget
      and may call for a reconsideration of the role of natural methane sources in past
      climate change.

PMID- 16407950
TI  - Stability of hydrous melt at the base of the Earth's upper mantle.
AB  - Seismological observations have revealed the existence of low-velocity and high
      attenuation zones above the discontinuity at 410 km depth, at the base of the
      Earth's upper mantle. It has been suggested that a small amount of melt could be
      responsible for such anomalies. The density of silicate melt under dry conditions
      has been measured at high pressure and found to be denser than the surrounding
      solid, thereby allowing the melt to remain at depth. But no experimental
      investigation of the density of hydrous melt has yet been carried out. Here we
      present data constraining the density of hydrous basaltic melt under pressure to
      examine the stability of melt above the 410-km discontinuity. We infer that
      hydrous magma formed by partial melting above the 410-km discontinuity may indeed
      be gravitationally stable, thereby supporting the idea that low-velocity or high
      attentuation regions just above the mantle transition zone may result from the
      presence of melt.

PMID- 16407951
TI  - A Cretaceous symmetrodont therian with some monotreme-like postcranial features.
AB  - A new spalacotheriid mammal preserved with a complete postcranium and a partial
      skull has been discovered from the Yixian Formation of Liaoning, China.
      Spalacotheroid symmetrodonts are relatives to modern therians (combined group of
      marsupials and placentals) and are characterized by many skeletal apomorphies of
      therians. But unlike the closely related spalacotheroids and living therians,
      this new mammal revealed some surprisingly convergent features to monotremes in
      the lumbar vertebrae, pelvis and hindlimb. These peculiar features may have
      developed as functional convergence to locomotory features of monotremes, or the
      presence of lumbar ribs in this newly discovered mammal and their absence in its
      close relatives might be due to evolutionary developmental homoplasy. Analysis
      including this new taxon suggests that spalacotheroids evolved earlier in Eurasia
      and then dispersed to North America, in concordance with prevailing geodispersal
      patterns of several common mammalian groups during the Early Cretaceous period.

PMID- 16407952
TI  - Outbred embryos rescue inbred half-siblings in mixed-paternity broods of live
      bearing females.
AB  - Females commonly mate with more than one male, and polyandry has been shown to
      increase reproductive success in many species. Insemination by multiple males
      shifts the arena for sexual selection from the external environment to the female
      reproductive tract, where sperm competition or female choice of sperm could bias
      fertilization against sperm from genetically inferior or genetically incompatible
      males. Evidence that polyandry can be a strategy for avoiding incompatibility
      comes from studies showing that inbreeding cost is reduced in some egg-laying
      species by postcopulatory mechanisms that favour fertilization by sperm from
      unrelated males. In viviparous (live-bearing) species, inbreeding not only
      reduces offspring genetic quality but might also disrupt feto-maternal
      interactions that are crucial for normal embryonic development. Here we show that
      polyandry in viviparous pseudoscorpions reduces inbreeding cost not through
      paternity-biasing mechanisms favouring outbred offspring, but rather because
      outbred embryos exert a rescuing effect on inbred half-siblings in mixed
      paternity broods. The benefits of polyandry may thus be more complex for live
      bearing females than for females that lay eggs.

PMID- 16407953
TI  - Planar cell polarity signalling couples cell division and morphogenesis during
      neurulation.
AB  - Environmental and genetic aberrations lead to neural tube closure defects (NTDs)
      in 1 out of every 1,000 births. Mouse and frog models for these birth defects
      have indicated that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other
      components of planar cell polarity (PCP) signalling might control neurulation by
      promoting the convergence of neural progenitors to the midline. Here we show a
      novel role for PCP signalling during neurulation in zebrafish. We demonstrate
      that non-canonical Wnt/PCP signalling polarizes neural progenitors along the
      anteroposterior axis. This polarity is transiently lost during cell division in
      the neural keel but is re-established as daughter cells reintegrate into the
      neuroepithelium. Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the
      polarization of neural keel cells, disrupts re-intercalation of daughter cells
      into the neuroepithelium, and results in ectopic neural progenitor accumulations
      and NTDs. Remarkably, blocking cell division leads to rescue of trilobite neural
      tube morphogenesis despite persistent defects in convergence and extension. These
      results reveal a function for PCP signalling in coupling cell division and
      morphogenesis at neurulation and indicate a previously unrecognized mechanism
      that might underlie NTDs.

PMID- 16407954
TI  - Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk.
AB  - The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely
      packed cellular structures in eukaryotic cells. It provides the architectural
      framework for assembling and anchoring the largest known muscle filament systems
      by an extensive network of protein-protein interactions, requiring an
      extraordinary level of mechanical stability. Here we show, using X-ray
      crystallography, how the amino terminus of the longest filament component, the
      giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich
      complex by the Z-disk ligand telethonin. The pseudosymmetric structure of
      telethonin mediates a unique palindromic arrangement of two titin filaments, a
      type of molecular assembly previously found only in protein-DNA complexes. We
      have confirmed its unique architecture in vivo by protein complementation assays,
      and in vitro by experiments using fluorescence resonance energy transfer. The
      model proposed may provide a molecular paradigm of how major sarcomeric filaments
      are crosslinked, anchored and aligned within complex cytoskeletal networks.

PMID- 16407955
TI  - Structure of the Sec13/31 COPII coat cage.
AB  - Endomembranes of eukaryotic cells are dynamic structures that are in continuous
      communication through the activity of specialized cellular machineries, such as
      the coat protein complex II (COPII), which mediates cargo export from the
      endoplasmic reticulum (ER). COPII consists of the Sar1 GTPase, Sec23 and Sec24
      (Sec23/24), where Sec23 is a Sar1-specific GTPase-activating protein and Sec24
      functions in cargo selection, and Sec13 and Sec31 (Sec13/31), which has a
      structural role. Whereas recent results have shown that Sec23/24 and Sec13/31 can
      self-assemble to form COPII cage-like particles, we now show that Sec13/31 can
      self-assemble to form minimal cages in the absence of Sec23/24. We present a
      three-dimensional reconstruction of these Sec13/31 cages at 30 A resolution using
      cryo-electron microscopy and single particle analysis. These results reveal a
      novel cuboctahedron geometry with the potential to form a flexible lattice and to
      generate a diverse range of containers. Our data are consistent with a model for
      COPII coat complex assembly in which Sec23/24 has a non-structural role as a
      multivalent ligand localizing the self-assembly of Sec13/31 to form a cage
      lattice driving ER cargo export.

PMID- 16407957
TI  - New directions for 2006.

PMID- 16407959
TI  - What factors are associated with neonatal injury following shoulder dystocia?
AB  - OBJECTIVE: To identify factors associated with the development of neonatal injury
      in the setting of shoulder dystocia. STUDY DESIGN: Medical record ICD-9 codes and
      a computerized perinatal database were reviewed to identify cases of shoulder
      dystocia from January 1996 to January 2001 in a tertiary care center. For
      confirmation of the diagnosis and collection of data, both maternal and neonatal
      charts were then reviewed and neonatal injuries categorized as either
      neurological (brachial plexus injury) or skeletal (clavicular fracture, humeral
      fracture). Shoulder dystocia cases were divided into groups based on the presence
      of neonatal injury at delivery or at discharge (with or without Erb's palsy). The
      group with neonatal injury was compared for demographic and obstetrical factors
      to the group without injury (control). chi (2) test, Mann-Whitney test and
      logistic regression were used as appropriate. RESULTS: During this 5-year period,
      there were 25,995 deliveries and 206 (0.8%) confirmed cases of shoulder dystocia.
      Of these cases, 36 (17.5%) had neonatal injury diagnosed at delivery and 25 (12%)
      remained with significant residual injury at discharge. Of these there were 19
      cases of Erb's palsy and six cases of clavicular fracture. No association was
      found between neonatal injury and maternal age, ethnicity, diabetes, operative
      vaginal delivery or number of obstetrical maneuvers. However, maternal body mass
      index >30 kg/m2, a second stage of labor >20 min and a birth weight >4500 g were
      all associated with an increased risk of neonatal injury at delivery and at
      discharge, including Erb's palsy. After logistic regression analysis, only a
      second stage of delivery >20 min remained significantly associated with neonatal
      injury at discharge. CONCLUSION: In our population, maternal obesity was
      associated with an increased risk of neonatal injury after shoulder dystocia. In
      addition, a short second stage of labor (<20 min) was associated with a lower
      rate of neonatal injury.

PMID- 16407960
TI  - A pilot trial testing the feasibility of administering D-penicillamine to
      extremely low birth weight neonates.
AB  - OBJECTIVE: We enterally administered a 14-day course of 3-mercapto-D-valine (D
      penicillamine) to five extremely low birth weight (ELBW) neonates, as a step
      toward assessing this therapy as a means of reducing the incidence or severity of
      retinopathy of prematurity (ROP). METHODS: The study drug (100 mg/ml) was given
      by nasogastric tube at a dose of 100 mg/k every 8 h for three days, and then 50
      mg/k once per day for 11 additional days. Logbooks were maintained by the bedside
      nurses to record signs of possible immediate intolerance. Laboratory tests
      assessed hepatic, renal, and hematologic toxicity. ROP was scored according to
      the ICROP guidelines. Comparisons were with a cohort of 139 consecutive recent
      neonates of the same birth weight and gestational age range. RESULTS: Five
      neonates were enrolled in the study, and all received the full course of study
      drug as planned. Signs of immediate intolerance of the study drug were not
      observed in any. The study patients did not have a higher incidence, than that of
      the cohort group, in creatinine elevation, thrombocytopenia, neutropenia,
      hyperbilirubinemia, or abnormal liver function test. Four of the five had no ROP
      and one developed transient stage 1, compared with a 54% occurrence of ROP in the
      cohort. CONCLUSIONS: It is feasible to enterally administer a 14-day course of 3
      mercapto-D-valine to ELBW neonates and the suspension appears to be well
      tolerated. These results suggest that phase II safety and preliminary efficacy
      trials can be undertaken.

PMID- 16407961
TI  - Umbilical cord nucleated red blood cell counts: normal values and the effect of
      labor.
AB  - OBJECTIVE: To determine the umbilical cord blood nucleated red blood cell (UC
      nRBC) count in uncomplicated pregnancies delivered by elective cesarean section
      or delivered vaginally. METHODS: A total of 57-term singleton pregnancies were
      studied: 33 with elective cesarean sections and 24 with vaginal deliveries. UC
      nRBC was analyzed for its nucleated red blood cell counts. A logarithmic
      transformation of the data was used for statistical analysis. RESULTS: The mean+/
      standard deviation (s.d.) for nucleated red blood cell per 100 white blood cells
      (nRBC/100WBC) from the elective cesarean section group was 7.8+/-7.4. The vaginal
      delivery group had a mean value of 9.3+/-10.5, which was not significantly
      different. A value of 22 nRBC/100WBC defined the upper 95% confidence limit. The
      correlation between absolute nRBC and nRBC/100 WBC was 0.97. CONCLUSION: Although
      chronic hypoxia is associated with elevated nRBC, the stress of uncomplicated
      labor does not change the level. This adds credence to its use as a marker for
      hypoxia preceding labor and delivery.

PMID- 16407962
TI  - Evaluation of a point-of-care direct spectrophotometric method for measurement of
      total serum bilirubin in term and near-term neonates.
AB  - OBJECTIVE: To evaluate point-of-care (POC) measurement of total serum bilirubin
      (TSB) in the management of neonatal jaundice. STUDY DESIGN: TSB was measured by a
      POC direct spectrophotometric bilirubin method (Unistat (U/TSB)) and a standard
      diazo clinical laboratory method (Olympus AU640E analyzer (diazo/TSB)). Agreement
      between U/TSB and diazo/TSB was assessed by correlation coefficient and Bland
      Altman analysis. Transcutaneous bilirubin (TcB) was measured using JM-103 (JM).
      RESULTS: Correlation between U/TSB and diazo/TSB was 0.99 (n = 120). Maximum
      difference (U/TSB minus diazo/TSB) was -2.9 mg/dl, and 79% were +/-1 mg/dl; the
      average difference was -0.37+/-0.70 mg/dl and the average absolute difference was
      0.60+/-0.52 mg/dl. Median time to determine U/TSB was 5 min. Correlation between
      U/TSB and JM was 0.92 (n = 113). Maximum difference (U/TSB minus JM) was 6.3
      mg/dl, and 45% were +/-1 mg/dl; the average difference was 0.7+/-1.8 mg/dl and
      the average absolute difference was 1.4+/-1.2 mg/dl. CONCLUSION: Measurement of
      TSB using Unistat provides excellent agreement with diazo/TSB and rapid
      turnaround time. This technique may provide reliable POC confirmation of TcB
      results that are above a screening cutoff value.

PMID- 16407963
TI  - The in utero passage of meconium by very low birth weight infants: a marker for
      adverse outcomes.
AB  - OBJECTIVES: To determine the incidence of in utero meconium passage and the rate
      of associated complications among VLBW infants. STUDY DESIGN: Retrospective
      review of medical records and prospective evaluation of placental samples from
      431 VLBW infants who survived >24 h. Cases with histologic evidence of meconium
      were re-examined and hemosiderin excluded by a negative iron stain. Statistical
      analysis included chi2, logistic regression, Student's t-test and Kruskal-Wallis.
      RESULTS: The 70 infants (16.2%) who had placental evidence of in utero meconium
      passage were younger, weighed less, and more likely to be delivered by C-section
      (P = 0.006), intubated in the delivery room (P = 0.02), receive chest
      compressions (P = 0.003), require volume resuscitation (P = 0.001) and develop
      grade III-IV intraventricular hemorrhages (P = 0.011) than were control infants.
      CONCLUSION: Microscopic evaluation of the placental membranes reveals that the in
      utero passage of meconium occurs in about 16% of premature infants and is
      associated with adverse perinatal outcomes, including the need for resuscitation
      at delivery and an increased risk for grade III-IV intraventricular hemorrhages.

PMID- 16407964
TI  - A descriptive model of preventability in maternal morbidity and mortality.
AB  - OBJECTIVE: To develop a descriptive model of preventability for maternal
      morbidity and mortality that can be used in quality assurance and morbidity and
      mortality review processes. STUDY DESIGN: This descriptive study was part of a
      larger case-control study conducted at the University of Illinois at Chicago in
      which maternal deaths were cases and women with severe maternal morbidity served
      as controls. Morbidities and mortalities were classified by a team of clinicians
      as preventable or not preventable. Qualitative analysis of data was conducted to
      identify and categorize different types of preventable events. RESULTS: Of 237
      women, there were 79 women with preventable events attributable to provider or
      system factors. The most common types of preventable events were inadequate
      diagnosis/recognition of high-risk (54.4%), treatment (38.0%), and documentation
      (30.7%). CONCLUSIONS: A descriptive model was illustrated that can be used to
      categorize preventable events in maternal morbidity and mortality and can be
      incorporated into quality assurance and clinical case review to enhance the
      monitoring of hospital-based obstetric care and to decrease medical error.

PMID- 16407965
TI  - Racial differences in prenatal care of mothers delivering very low birth weight
      infants.
AB  - OBJECTIVES: To determine whether there are any racial differences in the prenatal
      care of mothers delivering very low birth weight infants (VLBW). STUDY DESIGN:
      Retrospective cohort study of infants cared for at a single regional level III
      neonatal intensive care unit over a 9-year period, July 1993-June 2002, N = 1234.
      The main outcome variables investigated included antenatal administration of
      steroids, delivery by cesarean section, and use of tocolytic medications. Both
      univariate and multivariate analyses were performed. RESULTS: After controlling
      for potential confounding variables, white mothers delivering VLBWs had an
      increased odds of cesarean delivery (odds ratio 1.5, 95% confidence intervals
      (CI) 1.1-2.0), receiving antenatal steroids (1.3, CI 1.01-1.8), and tocolysis
      (1.4, CI 1.1-2.0) compared to black mothers. The models controlled for
      gestational age, multiple gestation, premature labor, clinical chorioamnionitis,
      maternal age, income, year of birth, and presentation. CONCLUSIONS: In our
      population of VLBWs, white mothers are more likely to receive antenatal steroids,
      tocolytic medications, and deliver by cesarean section when compared to black
      mothers. From our data we cannot determine the reasons behind these racial
      differences in care of mothers delivering VLBWs.

PMID- 16407966
TI  - Lipopolysaccharide-binding protein in noninfected neonates and those with
      suspected early-onset bacterial infection.
AB  - OBJECTIVES: To investigate postnatal lipopolysaccharide-binding protein (LBP)
      kinetics in term neonates and to test its diagnostic accuracy for early-onset
      bacterial infection (EOBI). STUDY DESIGN: A total of 99 neonates with clinical
      and serological signs of EOBI comprised the study group; 198 neonates with risk
      factors, but without EOBI, served as controls. LBP, C-reactive protein (CRP) and
      interleukin-8 (IL-8) were determined. RESULTS: LBP in the noninfected group
      increased until 24 h after birth (P < 0.05 vs 6 h). LBP and CRP correlated
      strongly in neonates with suspected EOBI (r = 0.63). Although LBP reached a
      higher sensitivity than CRP 6 and 12 h after clinical suspicion (45 (24-68) and
      79% (54-94) vs 9 (0-24) and 39% (17-64); P < 0.05)), EOBI was most reliably
      detected by IL-8. CONCLUSION: LBP kinetics were age-dependent. LBP was not
      sufficiently sensitive in the prediction of EOBI.

PMID- 16407967
TI  - Mild hypothermia via selective head cooling as neuroprotective therapy in term
      neonates with perinatal asphyxia: an experience from a single neonatal intensive
      care unit.
AB  - OBJECTIVE: The objective of this study was to determine the efficacy of mild
      hypothermia via selective head cooling as a neuroprotective therapy in term
      infants with perinatal asphyxia. STUDY DESIGN: Full-term newborns who had 5 min
      Apgar scores <6, first arterial blood gas pH<7.10 or BD>15 mEq/l, and with the
      clinical signs of encephalopathy were enrolled within 6 h after birth. Patients
      were randomized to receive mild hypothermia treatment via selective head cooling
      for a total of 72 h or receive routine treatment as a control. Brain hypoxic
      ischemic injury was quantified based on the head computed tomographic scan (CT
      scan) at postnatal age 5-7 days and a Neonatal Behavioral Neurological Assessment
      (NBNA) score at 7-10 days of life. RESULTS: A total of 58 patients (30
      hypothermia, 28 control) completed the study. Hypothermia was well tolerated in
      this study and attenuated the hypoxic-ischemic brain injury due to perinatal
      asphyxia. Head CT scan demonstrated moderate to severe hypoxic-ischemic changes
      in only 4/30 cases from the hypothermic group. In contrast, 18/28 cases in the
      control group showed moderate to severe hypoxic-ischemic changes (chi (2)=15.97,
      P<0.01). Brain hypothermia also significantly improved the NBNA score (32+/-2 in
      the hypothermic group vs 28+/-3 in the control group, P<0.01). CONCLUSIONS: Our
      results suggest that selective head cooling may be used as a neuroprotective
      therapy in term neonates with perinatal asphyxia. A long-term follow-up study is
      needed to further validate the results of this study.

PMID- 16407968
TI  - Dynamic study of the transition from hyaluronan- to integrin-mediated adhesion in
      chondrocytes.
AB  - Membrane-bound hyaluronan mediates the initial adhesive interactions between many
      cell types and external surfaces. In RCJ-P chondrocytes, such early contacts are
      mediated through a thick hyaluronidase-sensitive coat. The early adhesion is
      followed by integrin-mediated interactions and the formation of stable focal
      adhesions. During this process, the distance between the cell membrane and the
      surface is reduced from micrometers to few tens of nanometers. The transition
      from hyaluronan- to integrin-mediated adhesion was studied on glass surfaces by
      total internal reflection fluorescence microscopy. Hyaluronan-mediated adhesion
      precedes focal adhesions formation by 2-10 min. After these initial interactions,
      the pericellular hyaluronan remains sequestered into discrete pockets between the
      cell and the surface, which are a few hundreds nanometers thick and a few
      micrometers wide, and are flanked by focal adhesions. The hyaluronan coat
      facilitates the nucleation of small paxillin-rich contacts, which later mature
      into focal adhesions. These dynamic studies demonstrate that pericellular
      hyaluronan mediates initial cell-surface adhesion, and regulates the formation of
      focal adhesions.

PMID- 16407969
TI  - Antagonistic sensory cues generate gustatory plasticity in Caenorhabditis
      elegans.
AB  - Caenorhabditis elegans shows chemoattraction to 0.1-200 mM NaCl, avoidance of
      higher NaCl concentrations, and avoidance of otherwise attractive NaCl
      concentrations after prolonged exposure to NaCl (gustatory plasticity). Previous
      studies have shown that the ASE and ASH sensory neurons primarily mediate
      attraction and avoidance of NaCl, respectively. Here we show that balances
      between at least four sensory cell types, ASE, ASI, ASH, ADF and perhaps ADL,
      modulate the response to NaCl. Our results suggest that two NaCl-attraction
      signalling pathways exist, one of which uses Ca(2+)/cGMP signalling. In addition,
      we provide evidence that attraction to NaCl is antagonised by G-protein
      signalling in the ASH neurons, which is desensitised by the G-protein-coupled
      receptor kinase GRK-2. Finally, the response to NaCl is modulated by G-protein
      signalling in the ASI and ADF neurons, a second G-protein pathway in ASH and cGMP
      signalling in neurons exposed to the body fluid.

PMID- 16407970
TI  - SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation
      versus repair.
AB  - Mammals harbour multiple enzymes capable of excising uracil from DNA, although
      their distinct physiological roles remain uncertain. One of them (UNG) plays a
      critical role in antibody gene diversification, as UNG deficiency alone is
      sufficient to perturb the process. Here, we show this unique requirement for UNG
      does not reflect the fact that other glycosylases are unable to access the U:G
      lesion. SMUG1, if overexpressed, can partially substitute for UNG to assist
      antibody diversification as judged by its effect on somatic hypermutation
      patterns (in both DT40 B cells and mice) as well as a restoration of isotype
      switching in SMUG-transgenic msh2-/- ung-/- mice. However, SMUG1 plays little
      natural role in antibody diversification because (i) it is diminishingly
      expressed during B-cell activation and (ii) even if overexpressed, SMUG1 more
      appears to favour conventional repair of the uracil lesion than assist
      diversification. The distinction between UNG and overexpressed SMUG1 regarding
      the balance between antibody diversification and non-mutagenic repair of the U:G
      lesion could reflect the association of UNG (but not SMUG1) with sites of DNA
      replication.

PMID- 16407971
TI  - The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and
      Abeta generation in vivo.
AB  - The cholesterol-synthesizing enzyme seladin-1, encoded by the Dhcr24 gene, is a
      flavin adenine dinucleotide-dependent oxidoreductase and regulates responses to
      oncogenic and oxidative stimuli. It has a role in neuroprotection and is
      downregulated in affected neurons in Alzheimer's disease (AD). Here we show that
      seladin-1-deficient mouse brains had reduced levels of cholesterol and
      disorganized cholesterol-rich detergent-resistant membrane domains (DRMs). This
      was associated with inefficient plasminogen binding and plasmin activation, the
      displacement of beta-secretase (BACE) from DRMs to APP-containing membrane
      fractions, increased beta-cleavage of APP and high levels of Abeta peptides. In
      contrast, overexpression of seladin-1 increased both cholesterol and the
      recruitment of DRM components into DRM fractions, induced plasmin activation and
      reduced both BACE processing of APP and Abeta formation. These results establish
      a role of seladin-1 in the formation of DRMs and suggest that seladin-1-dependent
      cholesterol synthesis is involved in lowering Abeta levels. Pharmacological
      enhancement of seladin-1 activity may be a novel Abeta-lowering approach for the
      treatment of AD.

PMID- 16407972
TI  - Processive movement of single kinesins on crowded microtubules visualized using
      quantum dots.
AB  - Kinesin-1 is a processive molecular motor transporting cargo along microtubules.
      Inside cells, several motors and microtubule-associated proteins compete for
      binding to microtubules. Therefore, the question arises how processive movement
      of kinesin-1 is affected by crowding on the microtubule. Here we use total
      internal reflection fluorescence microscopy to image in vitro the runs of single
      quantum dot-labelled kinesins on crowded microtubules under steady-state
      conditions and to measure the degree of crowding on a microtubule at steady
      state. We find that the runs of kinesins are little affected by high kinesin
      densities on a microtubule. However, the presence of high densities of a mutant
      kinesin that is not able to step efficiently reduces the average speed of wild
      type kinesin, while hardly changing its processivity. This indicates that kinesin
      waits in a strongly bound state on the microtubule when encountering an obstacle
      until the obstacle unbinds and frees the binding site for kinesin's next step. A
      simple kinetic model can explain quantitatively the behaviour of kinesin under
      both crowding conditions.

PMID- 16407973
TI  - Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the
      authorization of repair.
AB  - MutS plays a critical role in DNA mismatch repair in Escherichia coli by binding
      to mismatches and initiating repair in an ATP-dependent manner. Mutational
      analysis of a highly conserved glutamate, Glu38, has revealed its role in
      mismatch recognition by enabling MutS to discriminate between homoduplex and
      mismatched DNA. Crystal structures of MutS have shown that Glu38 forms a hydrogen
      bond to one of the mismatched bases. In this study, we have analyzed the crystal
      structures, DNA binding and the response to ATP binding of three Glu38 mutants.
      While confirming the role of the negative charge in initial discrimination, we
      show that in vivo mismatch repair can proceed even when discrimination is low. We
      demonstrate that the formation of a hydrogen bond by residue 38 to the mismatched
      base authorizes repair by inducing intramolecular signaling, which results in the
      inhibition of rapid hydrolysis of distally bound ATP. This allows formation of
      the stable MutS-ATP-DNA clamp, a key intermediate in triggering downstream repair
      events.

PMID- 16407974
TI  - ETO2 coordinates cellular proliferation and differentiation during
      erythropoiesis.
AB  - The passage from proliferation to terminal differentiation is critical for normal
      development and is often perturbed in malignancies. To define the molecular
      mechanisms that govern this process during erythropoiesis, we have used
      tagging/proteomics approaches and characterized protein complexes nucleated by
      TAL-1/SCL, a basic helix-loop-helix transcription factor that specifies the
      erythrocytic lineage. In addition to known TAL-1 partners, GATA-1, E2A, HEB, LMO2
      and Ldb1, we identify the ETO2 repressor as a novel component recruited to TAL-1
      complexes through interaction with E2A/HEB. Ectopic expression and siRNA
      knockdown experiments in hematopoietic progenitor cells show that ETO2 actively
      represses erythroid TAL-1 target genes and governs the expansion of erythroid
      progenitors. At the onset of erythroid differentiation, a change in the
      stoichiometry of ETO2 within the TAL-1 complex activates the expression of known
      erythroid-specific TAL-1 target genes and of Gfi-1b and p21(Cip), encoding two
      essential regulators of erythroid cell proliferation. These results suggest that
      the dynamics of ETO2 recruitment within nuclear complexes couple cell
      proliferation to cell differentiation and determine the onset of terminal
      erythroid maturation.

PMID- 16407975
TI  - Initiation of DNA repair mediated by a stalled RNA polymerase IIO.
AB  - The transcription-coupled repair (TCR) pathway preferentially repairs DNA damage
      located in the transcribed strand of an active gene. To gain insight into the
      coupling mechanism between transcription and repair, we have set up an in vitro
      system in which we isolate an elongating RNA pol IIO, which is stalled in front
      of a cisplatin adduct. This immobilized RNA pol IIO is used as 'bait' to
      sequentially recruit TFIIH, XPA, RPA, XPG and XPF repair factors in an ATP
      dependent manner. This RNA pol IIO/repair complex allows the ATP-dependent
      removal of the lesion only in the presence of CSB, while the latter does not
      promote dual incision in an XPC-dependent nucleotide excision repair reaction. In
      parallel to the dual incision, the repair factors also allow the partial release
      of RNA pol IIO. In this 'minimal TCR system', the RNA pol IIO can effectively act
      as a loading point for all the repair factors required to eliminate a
      transcription-blocking lesion.

PMID- 16407976
TI  - Selective inhibition of the Fc epsilon RI-induced de novo synthesis of mediators
      by an inhibitory receptor.
AB  - Aggregation of the type 1 Fc-epsilon receptors (Fc-epsilon-RI) on mast cells
      initiates a network of biochemical processes culminating in secretion of both
      granule-stored and de novo-synthesized inflammatory mediators. A strict control
      of this response is obviously a necessity; nevertheless, this regulation is
      hardly characterized. Here we report that a prototype inhibitory receptor, the
      mast cell function-associated antigen (MAFA), selectively regulates the Fc
      epsilon-RI stimulus-response coupling network and the subsequent de novo
      production and secretion of inflammatory mediators. Specifically, MAFA suppresses
      the PLC-gamma2-[Ca2+]i, Raf-1-Erk1/2, and PKC-p38 coupling pathways, while the
      Fyn-Gab2-mediated activation of PKB and Jnk is essentially unaffected. Hence, the
      activities of several transcription/nuclear factors for inflammatory mediators
      (NF-kappaB, NFAT) are markedly reduced, while those of others (Jun, Fos, Fra,
      p90rsk) are unaltered. This results in a selective inhibition of gene
      transcription of cytokines including IL-1beta, IL-4, IL-8, and IL-10, while that
      of TNF-alpha, MCP-1, IL-3, IL-5, or IL-13 remains unaffected. Taken together,
      these results illustrate the capacity of an immunoreceptor tyrosine-based
      inhibitory motif-containing receptor to cause tight and specific control of the
      production and secretion of inflammatory mediators by mast cells.

PMID- 16407977
TI  - TRPM7, a novel regulator of actomyosin contractility and cell adhesion.
AB  - Actomyosin contractility regulates various cell biological processes including
      cytokinesis, adhesion and migration. While in lower eukaryotes, alpha-kinases
      control actomyosin relaxation, a similar role for mammalian alpha-kinases has yet
      to be established. Here, we examined whether TRPM7, a cation channel fused to an
      alpha-kinase, can affect actomyosin function. We demonstrate that activation of
      TRPM7 by bradykinin leads to a Ca(2+)- and kinase-dependent interaction with the
      actomyosin cytoskeleton. Moreover, TRPM7 phosphorylates the myosin IIA heavy
      chain. Accordingly, low overexpression of TRPM7 increases intracellular Ca2+
      levels accompanied by cell spreading, adhesion and the formation of focal
      adhesions. Activation of TRPM7 induces the transformation of these focal
      adhesions into podosomes by a kinase-dependent mechanism, an effect that can be
      mimicked by pharmacological inhibition of myosin II. Collectively, our results
      demonstrate that regulation of cell adhesion by TRPM7 is the combined effect of
      kinase-dependent and -independent pathways on actomyosin contractility.

PMID- 16407982
TI  - Ribonucleic general acid.

PMID- 16407978
TI  - The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90.
AB  - Ppt1 is the yeast member of a novel family of protein phosphatases, which is
      characterized by the presence of a tetratricopeptide repeat (TPR) domain. Ppt1 is
      known to bind to Hsp90, a molecular chaperone that performs essential functions
      in the folding and activation of a large number of client proteins. The function
      of Ppt1 in the Hsp90 chaperone cycle remained unknown. Here, we analyzed the
      function of Ppt1 in vivo and in vitro. We show that purified Ppt1 specifically
      dephosphorylates Hsp90. This activity requires Hsp90 to be directly attached to
      Ppt1 via its TPR domain. Deletion of the ppt1 gene leads to hyperphosphorylation
      of Hsp90 in vivo and an apparent decrease in the efficiency of the Hsp90
      chaperone system. Interestingly, several Hsp90 client proteins were affected in a
      distinct manner. Our findings indicate that the Hsp90 multichaperone cycle is
      more complex than was previously thought. Besides its regulation via the Hsp90
      ATPase activity and the sequential binding and release of cochaperones, with
      Ppt1, a specific phosphatase exists, which positively modulates the maturation of
      Hsp90 client proteins.

PMID- 16407979
TI  - Essential roles for the FE65 amyloid precursor protein-interacting proteins in
      brain development.
AB  - Targeted deletion of two members of the FE65 family of adaptor proteins, FE65 and
      FE65L1, results in cortical dysplasia. Heterotopias resembling those found in
      cobblestone lissencephalies in which neuroepithelial cells migrate into
      superficial layers of the developing cortex, aberrant cortical projections and
      loss of infrapyramidal mossy fibers arise in FE65/FE65L1 compound null animals,
      but not in single gene knockouts. The disruption of pial basal membranes
      underlying the heterotopias and poor organization of fibrillar laminin by
      isolated meningeal fibroblasts from double knockouts suggests that FE65 proteins
      are involved in basement membrane assembly. A similar phenotype is observed in
      triple mutant mice lacking the APP family members APP, APLP1 and APLP2, all of
      which interact with FE65 proteins, suggesting that this phenotype may be caused
      by decreased transmission of an APP-dependent signal through the FE65 proteins.
      The defects observed in the double knockout may also involve the family of
      Ena/Vasp proteins, which participate in actin cytoskeleton remodeling and
      interact with the WW domains of FE65 proteins.

PMID- 16407983
TI  - Pulling NO out of thin air.

PMID- 16407984
TI  - Trp modification signals a quorum.

PMID- 16407985
TI  - Ending the prolonged life of cancer cells.

PMID- 16407987
TI  - Chemistry in living systems.
AB  - Dissecting complex cellular processes requires the ability to track biomolecules
      as they function within their native habitat. Although genetically encoded tags
      such as GFP are widely used to monitor discrete proteins, they can cause
      significant perturbations to a protein's structure and have no direct extension
      to other classes of biomolecules such as glycans, lipids, nucleic acids and
      secondary metabolites. In recent years, an alternative tool for tagging
      biomolecules has emerged from the chemical biology community--the bioorthogonal
      chemical reporter. In a prototypical experiment, a unique chemical motif, often
      as small as a single functional group, is incorporated into the target
      biomolecule using the cell's own biosynthetic machinery. The chemical reporter is
      then covalently modified in a highly selective fashion with an exogenously
      delivered probe. This review highlights the development of bioorthogonal chemical
      reporters and reactions and their application in living systems.

PMID- 16407988
TI  - Structure of the Bacillus subtilis quorum-sensing peptide pheromone ComX.
AB  - The ComX pheromone is an extracellular signaling molecule that stimulates natural
      competence in response to crowding in the gram-positive bacterium Bacillus
      subtilis. The pheromone is formed by isoprenylation of an inactive precursor
      peptide, but its precise structure is not known. Here we report the structure of
      the ComX pheromone, showing that addition of a geranyl group to a tryptophan
      residue results in the formation of an unusual ring structure.

PMID- 16407989
TI  - Molecular basis of inverse agonism in a G protein-coupled receptor.
AB  - G protein-coupled receptors (GPCRs) recognize a wide variety of extracellular
      ligands to control diverse physiological processes. Compounds that bind to such
      receptors can either stimulate, fully or partially (full or partial agonists), or
      reduce (inverse agonists) the receptors' basal activity and receptor-mediated
      signaling. Various studies have shown that the activation of receptors through
      binding of agonists proceeds by conformational changes as the receptor switches
      from a resting to an active state leading to G protein signaling. Yet the
      molecular basis for differences between agonists and inverse agonists is unclear.
      These different classes of compounds are assumed to switch the receptors'
      conformation in distinct ways. It is not known, however, whether such switching
      occurs along a linear 'on-off' scale or whether agonists and inverse agonists
      induce different switch mechanisms. Using a fluorescence-based approach to study
      the alpha2A-adrenergic receptor (alpha(2A)AR), we show that inverse agonists are
      differentiated from agonists in that they trigger a very distinct mode of a
      receptor's switch. This switch couples inverse agonist binding to the suppression
      of activity in the receptor.

PMID- 16407990
TI  - Small-molecule inhibition of siderophore biosynthesis in Mycobacterium
      tuberculosis and Yersinia pestis.
AB  - Mycobacterium tuberculosis and Yersinia pestis, the causative agents of
      tuberculosis and plague, respectively, are pathogens with serious ongoing impact
      on global public health and potential use as agents of bioterrorism. Both
      pathogens have iron acquisition systems based on siderophores, secreted iron
      chelating compounds with extremely high Fe3+ affinity. Several lines of evidence
      suggest that siderophores have a critical role in bacterial iron acquisition
      inside the human host, where the free iron concentration is well below that
      required for bacterial growth and virulence. Thus, siderophore biosynthesis is an
      attractive target in the development of new antibiotics to treat tuberculosis and
      plague. In particular, such drugs, alone or as part of combination therapies,
      could provide a valuable new line of defense against intractable multiple-drug
      resistant infections. Here, we report the design, synthesis and biological
      evaluation of a mechanism-based inhibitor of domain salicylation enzymes required
      for siderophore biosynthesis in M. tuberculosis and Y. pestis. This new
      antibiotic inhibits siderophore biosynthesis and growth of M. tuberculosis and Y.
      pestis under iron-limiting conditions.

PMID- 16407991
TI  - Activity-based probes that target diverse cysteine protease families.
AB  - Proteases are one of the largest and best-characterized families of enzymes in
      the human proteome. Unfortunately, the understanding of protease function in the
      context of complex proteolytic cascades remains in its infancy. One major reason
      for this gap in understanding is the lack of technologies that allow direct
      assessment of protease activity. We report here an optimized solid-phase
      synthesis protocol that allows rapid generation of activity-based probes (ABPs)
      targeting a range of cysteine protease families. These reagents selectively form
      covalent bonds with the active-site thiol of a cysteine protease, allowing direct
      biochemical profiling of protease activities in complex proteomes. We present a
      number of probes containing either a single amino acid or an extended peptide
      sequence that target caspases, legumains, gingipains and cathepsins. Biochemical
      studies using these reagents highlight their overall utility and provide insight
      into the biochemical functions of members of these protease families.

PMID- 16407992
TI  - Small-molecule ligand induces nucleotide flipping in (CAG)n trinucleotide
      repeats.
AB  - DNA trinucleotide repeats, particularly CXG, are common within the human genome.
      However, expansion of trinucleotide repeats is associated with a number of
      disorders, including Huntington disease, spinobulbar muscular atrophy and
      spinocerebellar ataxia. In these cases, the repeat length is known to correlate
      with decreased age of onset and disease severity. Repeat expansion of (CAG)n,
      (CTG)n and (CGG)n trinucleotides may be related to the increased stability of
      alternative DNA hairpin structures consisting of CXG-CXG triads with X-X
      mismatches. Small-molecule ligands that selectively bound to CAG repeats could
      provide an important probe for determining repeat length and an important tool
      for investigating the in vivo repeat extension mechanism. Here we report that
      napthyridine-azaquinolone (NA, 1) is a ligand for CAG repeats and can be used as
      a diagnostic tool for determining repeat length. We show by NMR spectroscopy that
      binding of NA to CAG repeats induces the extrusion of a cytidine nucleotide from
      the DNA helix.

PMID- 16407993
TI  - General acid catalysis by the hepatitis delta virus ribozyme.
AB  - Recent crystallographic and functional analyses of RNA enzymes have raised the
      possibility that the purine and pyrimidine nucleobases may function as general
      acid-base catalysts. However, this mode of nucleobase-mediated catalysis has been
      difficult to establish unambiguously. Here, we used a hyperactivated RNA
      substrate bearing a 5'-phosphorothiolate to investigate the role of a critical
      cytosine residue in the hepatitis delta virus ribozyme. The hyperactivated
      substrate specifically suppressed the deleterious effects of cytosine mutations
      and pH changes, thereby linking the protonation of the nucleobase to leaving
      group stabilization. We conclude that the active-site cytosine provides general
      acid catalysis, mediating proton transfer to the leaving group through a
      protonated N3-imino nitrogen. These results establish a specific role for a
      nucleobase in a ribozyme reaction and support the proposal that RNA nucleobases
      may function in a manner analogous to that of catalytic histidine residues in
      protein enzymes.

PMID- 16407997
TI  - Small molecules: the missing link in the central dogma.
AB  - Small molecules have critical roles at all levels of biological complexity and
      yet remain orphans of the central dogma. Chemical biologists, working with small
      molecules, expand our understanding of these central elements of life.

PMID- 16407994
TI  - A molecular basis for NO selectivity in soluble guanylate cyclase.
AB  - Soluble guanylate cyclases (sGCs) function as heme sensors that selectively bind
      nitric oxide (NO), triggering reactions essential to animal physiology. Recent
      discoveries place sGCs in the H-NOX family (heme nitric oxide/oxygen-binding
      domain), which includes bacterial proteins from aerobic and anaerobic organisms.
      Some H-NOX proteins tightly bind oxygen (O2), whereas others show no measurable
      affinity for O2, providing the basis for selective NO signaling in aerobic cells.
      Using a series of wild-type and mutant H-NOXs, we established a molecular basis
      for ligand discrimination. A distal pocket tyrosine is requisite for O2 binding
      in the H-NOX family. These data suggest that sGC uses a kinetic selection against
      O2; we propose that the O2 dissociation rate in the absence of this tyrosine is
      fast and that a stable O2 complex does not form.

PMID- 16407998
TI  - Viral RNA gymnastics.
AB  - Retroviruses have a stretch of RNA that dimerizes during viral particle
      formation. A new study suggests that RNA flexibility in the monomeric form may
      facilitate dimerization or other RNA-dependent viral functions.

PMID- 16407999
TI  - Probing cell death by chemical screening.
AB  - Apoptosis occurs through precise cellular pathways, whereas necrosis is generally
      thought of as a nonspecific cellular response to external damage. However,
      identification of a chemical inhibitor of necrotic events suggests that specific
      molecular pathways can also trigger necrosis.

PMID- 16408000
TI  - A photochemical snapshot of CD22 binding.
AB  - Identification of endogenous glycan-binding ligands for cell-surface receptors
      has been difficult. Incorporation of a photoactive sialic acid analog into B-cell
      surface glycoproteins suggests that CD22 molecules may cluster by binding
      carbohydrate antigens on neighboring CD22 molecules.

PMID- 16408001
TI  - Relaxed specificity in aromatic prenyltransferases.
AB  - Prenylation represent a critical step in the biosynthesis of many natural
      products, A new study reveals how aromatic prenyltransferase enzymes tolerate
      diverse aromatic polyketides while still controlling the length of prenyl side
      chains.

PMID- 16408003
TI  - Diversity-oriented synthesis: exploring the intersections between chemistry and
      biology.
AB  - Diversity-oriented synthesis (DOS) is an emerging field involving the synthesis
      of combinatorial libraries of diverse small molecules for biological screening.
      Rather than being directed toward a single biological target, DOS libraries can
      be used to identify new ligands for a variety of targets. Several different
      strategies for library design have been developed to target the biologically
      relevant regions of chemical structure space. DOS has provided powerful probes to
      investigate biological mechanisms and also served as a new driving force for
      advancing synthetic organic chemistry.

PMID- 16408004
TI  - Sensing with TRP channels.
AB  - Drosophila melanogaster flies carrying the trp (transient receptor potential)
      mutation are rapidly blinded by bright light, because of the absence of a Ca2+
      permeable ion channel in their photoreceptors. The identification of the trp gene
      and the search for homologs in yeast, flies, worms, zebrafish and mammals has led
      to the discovery of a large superfamily of related cation channels, named TRP
      channels. Activation of TRP channels is highly sensitive to a variety of chemical
      and physical stimuli, allowing them to function as dedicated biological sensors
      that are essential in processes such as vision, taste, tactile sensation and
      hearing.

PMID- 16408005
TI  - Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross
      linking.
AB  - CD22 is a negative regulator of B-cell receptor signaling, an activity mediated
      by recruitment of SH2 domain-containing phosphatase 1 through a phosphorylated
      immunoreceptor tyrosine inhibitory motif in its cytoplasmic domain. As in other
      members of the sialic acid-binding immunoglobulin-like lectin, or siglec, family,
      the extracellular N-terminal immunoglobulin domain of CD22 binds to glycan
      ligands containing sialic acid, which are highly expressed on B-cell
      glycoproteins. B-cell glycoproteins bind to CD22 in cis and 'mask' the ligand
      binding domain, modulating its activity as a regulator of B-cell signaling. To
      assess cell-surface cis ligand interactions, we developed a new method for in
      situ photoaffinity cross-linking of glycan ligands to CD22. Notably, CD45,
      surfaceIgM (sIgM) and other glycoproteins that bind to CD22 in vitro do not
      appear to be important cis ligands of CD22 in situ. Instead, CD22 seems to
      recognize glycans of neighboring CD22 molecules as cis ligands, forming
      homomultimeric complexes.

PMID- 16408006
TI  - Linking agonist binding to histamine H1 receptor activation.
AB  - G protein-coupled receptors (GPCRs) constitute a large and functionally diverse
      family of transmembrane proteins. They are fundamental in the transfer of
      extracellular stimuli to intracellular signaling pathways and are among the most
      targeted proteins in drug discovery. The detailed molecular mechanism for agonist
      induced activation of rhodopsin-like GPCRs has not yet been described. Using a
      combination of site-directed mutagenesis and molecular modeling, we characterized
      important steps in the activation of the human histamine H1 receptor. Both
      Ser3.36 and Asn7.45 are important links between histamine binding and previously
      proposed conformational changes in helices 6 and 7. Ser3.36 acts as a rotamer
      toggle switch that, upon agonist binding, initiates the activation of the
      receptor through Asn7.45. The proposed transduction involves specific residues
      that are conserved among rhodopsin-like GPCRs.

PMID- 16408007
TI  - RNA flexibility in the dimerization domain of a gamma retrovirus.
AB  - Retroviruses are the causative agents of serious diseases, such as acquired
      immunodeficiency syndromes and several cancers, and are also useful gene therapy
      vectors. Retroviruses contain two sense-strand RNA genomes, which become linked
      at their 5' ends to form an RNA dimer. Understanding the molecular basis for
      dimerization may yield new approaches for controlling viral infectivity. Because
      this RNA domain is highly conserved within retrovirus groups, it has not been
      possible to define a consensus structure for the 5' dimerization domain by
      comparative sequence analysis. Here, we defined a 170-nucleotide minimal
      dimerization active sequence (MiDAS) for a representative gamma retrovirus, the
      Moloney murine sarcoma virus, by stringent competitive dimerization. We then
      analyzed the structure at every nucleotide in the MiDAS monomeric starting state
      with quantitative selective 2'-hydroxyl acylation analyzed by primer extension
      (SHAPE) chemistry. Notably, SHAPE analysis demonstrated that the RNA monomer
      contains an extensive flexible domain spanning 50 nucleotides. These findings
      support a structural model in which RNA flexibility directly facilitates
      retroviral genome dimerization by reducing the energetic cost of disrupting pre
      existing base pairings in the monomer.

PMID- 16408010
TI  - An emerging role for chemical biology.

PMID- 16408008
TI  - Chemical inhibitor of nonapoptotic cell death with therapeutic potential for
      ischemic brain injury.
AB  - The mechanism of apoptosis has been extensively characterized over the past
      decade, but little is known about alternative forms of regulated cell death.
      Although stimulation of the Fas/TNFR receptor family triggers a canonical
      'extrinsic' apoptosis pathway, we demonstrated that in the absence of
      intracellular apoptotic signaling it is capable of activating a common
      nonapoptotic death pathway, which we term necroptosis. We showed that necroptosis
      is characterized by necrotic cell death morphology and activation of autophagy.
      We identified a specific and potent small-molecule inhibitor of necroptosis,
      necrostatin-1, which blocks a critical step in necroptosis. We demonstrated that
      necroptosis contributes to delayed mouse ischemic brain injury in vivo through a
      mechanism distinct from that of apoptosis and offers a new therapeutic target for
      stroke with an extended window for neuroprotection. Our study identifies a
      previously undescribed basic cell-death pathway with potentially broad relevance
      to human pathologies.

PMID- 16408011
TI  - Natural insights for chemical biologists.
AB  - Chemical biologists studying natural-product pathways encoded in genomes have
      unearthed new chemistry and insights into the evolution of biologically active
      metabolites.

PMID- 16408012
TI  - New screening tools for lead compound identification.

PMID- 16408013
TI  - Controlled S-nitrosation.

PMID- 16408014
TI  - Getting the iron out.

PMID- 16408016
TI  - Assignment of protein function in the postgenomic era.
AB  - Genome sequencing projects have provided researchers with an unprecedented boon
      of molecular information that promises to revolutionize our understanding of life
      and lead to new treatments of its disorders. However, genome sequences alone
      offer only limited insights into the biochemical pathways that determine cell and
      tissue function. These complex metabolic and signaling networks are largely
      mediated by proteins. The vast number of uncharacterized proteins found in
      prokaryotic and eukaryotic systems suggests that our knowledge of cellular
      biochemistry is far from complete. Here, we highlight a new breed of
      'postgenomic' methods that aim to assign functions to proteins through the
      integrated application of chemical and biological techniques.

PMID- 16408017
TI  - Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3
      9.
AB  - Histone methylation plays a key role in establishing and maintaining stable gene
      expression patterns during cellular differentiation and embryonic development.
      Here, we report the characterization of the fungal metabolite chaetocin as the
      first inhibitor of a lysine-specific histone methyltransferase. Chaetocin is
      specific for the methyltransferase SU(VAR)3-9 both in vitro and in vivo and may
      therefore be used to study heterochromatin-mediated gene repression.

PMID- 16408018
TI  - High-throughput assays for promiscuous inhibitors.
AB  - High-throughput screening (HTS) searches large libraries of chemical compounds
      for those that can modulate the activity of a particular biological target; it is
      the dominant technique used in early-stage drug discovery. A key problem in HTS
      is the prevalence of nonspecific or 'promiscuous' inhibitors. These molecules
      have peculiar properties, act on unrelated targets and can dominate the results
      from screening campaigns. Several explanations have been proposed to account for
      promiscuous inhibitors, including chemical reactivity, interference in assay read
      out, high molecular flexibility and hydrophobicity. The diversity of these models
      reflects the apparently unrelated molecules whose behaviors they seek to explain.
      However, a single mechanism may explain the effects of many promiscuous
      inhibitors: some organic molecules form large colloid-like aggregates that
      sequester and thereby inhibit enzymes. Hits from HTS, leads for drug discovery
      and even several drugs appear to act through this mechanism at micromolar
      concentrations. Here, we report two rapid assays for detecting promiscuous
      aggregates that we tested against 1,030 'drug-like' molecules. The results from
      these assays were used to test two preliminary computational models of this
      phenomenon and as benchmarks to develop new models.

PMID- 16408019
TI  - Mycobactin-mediated iron acquisition within macrophages.
AB  - Restricting the availability of iron is an important strategy for defense against
      bacterial infection. Mycobacterium tuberculosis survives within the phagosomes of
      macrophages; consequently, iron acquisition is particularly difficult for M.
      tuberculosis, because the phagosomal membrane is an additional barrier for its
      iron access. However, little is known about the iron transport and acquisition
      pathways adapted by this microbe in vivo. Extracellular iron sources are usually
      mobilized by hydrophilic siderophores. Here, we describe direct evidence that
      mycobactins, the lipophilic siderophores of mycobacteria, efficiently extract
      intracellular macrophage iron. The metal-free siderophore is diffusely associated
      with the macrophage membrane, ready for iron chelation. Notably, the mycobactin
      metal complex accumulates with high selectivity in macrophage lipid droplets,
      intracellular domains for lipid storage and sorting. In our experiments, these
      mycobactin-targeted lipid droplets were found in direct contact with phagosomes,
      poised for iron delivery. The existence of this previously undescribed iron
      acquisition pathway indicates that mycobacteria have taken advantage of
      endogenous macrophage mechanisms for iron mobilization and lipid sorting for iron
      acquisition during infection. The pathway could represent a new target for the
      control of mycobacterial infection.

PMID- 16408020
TI  - Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine.
AB  - Nitric oxide (NO) signaling through the formation of cGMP is well established;
      however, there seems to be an increasing role for cGMP-independent NO signaling.
      Although key molecular details remain unanswered, S-nitrosation represents an
      example of cGMP-independent NO signaling. This modification has garnered recent
      attention as it has been shown to modulate the function of several important
      biochemical pathways. Although an analogy to O-phosphorylation can be drawn,
      little is known about protein nitrosothiol regulation in vivo. In solution, NO
      readily reacts with oxygen to yield a nitrosating agent, but this process alone
      provides no specificity for nitrosation. This lack of specificity is exemplified
      by the in vitro poly-S-nitrosation of caspase-3 (Casp-3, ref. 6) and the
      ryanodine receptor. Previous in vivo work with Casp-3 suggests that a protein
      assisted process may be responsible for selective S-nitrosation of the catalytic
      cysteine (Cys163). We demonstrated that a single cysteine in thioredoxin (Trx) is
      capable of a targeted, reversible transnitrosation reaction with Cys163 of Casp
      3. A greater understanding of how S-nitrosation is mediated has broad
      implications for cGMP-independent signaling. The example described here also
      suggests a new role for Trx in the regulation of apoptosis.

PMID- 16408021
TI  - A network of orthogonal ribosome x mRNA pairs.
AB  - Synthetic biology promises the ability to program cells with new functions.
      Simple oscillators, switches, logic functions, cell-cell communication and
      pattern-forming circuits have been created by the connection of a small set of
      natural transcription factors and their binding sites in different ways to
      produce different networks of molecular interactions. However, the controlled
      synthesis of more complex synthetic networks and functions will require an
      expanded set of functional molecules with known molecular specificities. Here, we
      tailored the molecular specificity of duplicated Escherichia coli ribosome x mRNA
      pairs with respect to the wild-type ribosome and mRNAs to produce multiple
      orthogonal ribosome x orthogonal mRNA pairs that can process information in
      parallel with, but independent of, their wild-type progenitors. In these pairs,
      the ribosome exclusively translates the orthogonal mRNA, and the orthogonal mRNA
      is not a substrate for cellular ribosomes. We predicted and measured the network
      of interactions between orthogonal ribosomes and orthogonal mRNAs, and showed
      that they can be used to post-transcriptionally program the cell with Boolean
      logic.

PMID- 16408024
TI  - Back to school.

PMID- 16408025
TI  - Teaching undergraduates at the interface of chemistry and biology: challenges and
      opportunities.

PMID- 16408026
TI  - Putting small molecules in the lead.

PMID- 16408022
TI  - Small-molecule interaction with a five-guanine-tract G-quadruplex structure from
      the human MYC promoter.
AB  - It has been widely accepted that DNA can adopt other biologically relevant
      structures beside the Watson-Crick double helix. One recent important example is
      the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in
      the MYC (or c-myc) promoter region, which regulates the transcription of the MYC
      oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic
      porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the
      first structure of a DNA fragment containing five guanine tracts from this
      region. An unusual G-quadruplex fold, which was derived from NMR restraints using
      unambiguous model-independent resonance assignment approaches, involves a core of
      three stacked guanine tetrads formed by four parallel guanine tracts with all
      anti guanines and a snapback 3'-end syn guanine. We have determined the structure
      of the complex formed between this G-quadruplex and TMPyP4. This structural
      information, combined with details of small-molecule interaction, provides a
      platform for the design of anticancer drugs targeting multi-guanine-tract
      sequences that are found in the MYC and other oncogenic promoters, as well as in
      telomeres.

PMID- 16408027
TI  - Imaging G protein-coupled receptor islands.

PMID- 16408028
TI  - Antigene leaps forward through an open door.

PMID- 16408029
TI  - Watching proteases in action.

PMID- 16408030
TI  - Cardiolipin oxidation sets cytochrome c free.

PMID- 16408031
TI  - A glimpse at the grail.

PMID- 16408032
TI  - The econometrics of evolution.

PMID- 16408033
TI  - Linking physiological functions of iron.

PMID- 16408035
TI  - Imaging nanometer domains of beta-adrenergic receptor complexes on the surface of
      cardiac myocytes.
AB  - The contraction of cardiac myocytes is initiated by ligand binding to adrenergic
      receptors contained in nanoscale multiprotein complexes called signalosomes. The
      composition and number of functional signalosomes within cardiac myocytes defines
      the molecular basis of the response to adrenergic stimuli. For the first time, we
      demonstrated the ability of near-field scanning optical microscopy to visualize
      beta-adrenergic receptors at the nanoscale in situ. On H9C2 cells, mouse neonatal
      and mouse embryonic cardiac myocytes, we showed that functional receptors are
      organized into multiprotein domains of approximately 140 nm average diameter.
      Colocalization experiments in primary cells at the nanometer scale showed that 15
      20% of receptors were preassociated in caveolae. These nanoscale complexes were
      sufficient to effect changes in ligand-induced contraction rate without the
      requirement for substantial changes in receptor distribution in the cellular
      membrane. Using fluorescence intensities associated with these nanodomains, we
      estimated the receptor density within the observed nanometer features and
      established a lower limit for the number of receptors in the signalosome.

PMID- 16408036
TI  - Dynamic imaging of protease activity with fluorescently quenched activity-based
      probes.
AB  - Protease activity is tightly regulated in both normal and disease conditions.
      However, it is often difficult to monitor the dynamic nature of this regulation
      in the context of a live cell or whole organism. To address this limitation, we
      developed a series of quenched activity-based probes (qABPs) that become
      fluorescent upon activity-dependent covalent modification of a protease target.
      These reagents freely penetrate cells and allow direct imaging of protease
      activity in living cells. Targeted proteases are directly identified and
      monitored biochemically by virtue of the resulting covalent tag, thereby allowing
      unambiguous assignment of protease activities observed in imaging studies. We
      report here the design and synthesis of a selective, cell-permeable qABP for the
      study of papain-family cysteine proteases. This probe is used to monitor real
      time protease activity in live human cells with fluorescence microscopy
      techniques as well as standard biochemical methods.

PMID- 16408037
TI  - Inhibiting transcription of chromosomal DNA with antigene peptide nucleic acids.
AB  - Synthetic molecules that recognize specific sequences within cellular DNA are
      potentially powerful tools for investigating chromosome structure and function.
      Here, we designed antigene peptide nucleic acids (agPNAs) to target the
      transcriptional start sites for the human progesterone receptor B (hPR-B) and A
      (hPR-A) isoforms at sequences predicted to be single-stranded within the open
      complex of chromosomal DNA. We found that the agPNAs were potent inhibitors of
      transcription, showing for the first time that synthetic molecules can recognize
      transcription start sites inside cells. Breast cancer cells treated with agPNAs
      showed marked changes in morphology and an unexpected relationship between the
      strictly regulated levels of hPR-B and hPR-A. We confirmed these phenotypes using
      siRNAs and antisense PNAs, demonstrating the power of combining antigene and
      antisense strategies for gene silencing. agPNAs provide a general approach for
      controlling transcription initiation and a distinct option for target validation
      and therapeutic development.

PMID- 16408038
TI  - Inhibiting gene expression at transcription start sites in chromosomal DNA with
      antigene RNAs.
AB  - Transcription start sites are critical switches for converting recognition of
      chromosomal DNA into active synthesis of RNA. Their functional importance
      suggests that they may be ideal targets for regulating gene expression. Here, we
      report potent inhibition of gene expression by antigene RNAs (agRNAs)
      complementary to transcription start sites within human chromosomal DNA.
      Silencing does not require methylation of DNA and differs from all known
      mechanisms for inhibiting transcription. agRNAs overlap DNA sequences within the
      open complex formed by RNA polymerase, and silencing is acutely sensitive to
      single base shifts. agRNAs effectively silence both TATA-less and TATA-box
      containing promoters. Transcription start sites occur within every gene,
      providing predictable targets for agRNAs. Potent inhibition of multiple genes
      suggests that agRNAs may represent a natural mechanism for controlling
      transcription, may complement siRNAs and miRNAs that target mRNA, and will be
      valuable agents for silencing gene expression.

PMID- 16408044
TI  - Meetings of the minds.

PMID- 16408039
TI  - Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic
      factors.
AB  - Programmed death (apoptosis) is turned on in damaged or unwanted cells to secure
      their clean and safe self-elimination. The initial apoptotic events are
      coordinated in mitochondria, whereby several proapoptotic factors, including
      cytochrome c, are released into the cytosol to trigger caspase cascades. The
      release mechanisms include interactions of B-cell/lymphoma 2 family proteins with
      a mitochondria-specific phospholipid, cardiolipin, to cause permeabilization of
      the outer mitochondrial membrane. Using oxidative lipidomics, we showed that
      cardiolipin is the only phospholipid in mitochondria that undergoes early
      oxidation during apoptosis. The oxidation is catalyzed by a cardiolipin-specific
      peroxidase activity of cardiolipin-bound cytochrome c. In a previously
      undescribed step in apoptosis, we showed that oxidized cardiolipin is required
      for the release of proapoptotic factors. These results provide insight into the
      role of reactive oxygen species in triggering the cell-death pathway and describe
      an early role for cytochrome c before caspase activation.

PMID- 16408045
TI  - Chemical biology: an educational challenge for chemistry departments.
AB  - Chemical biology, broadly defined as the application of chemistry to the study of
      molecular events in biological systems, presents an opportunity for the
      reorganization and revitalization of the chemistry curriculum.

PMID- 16408046
TI  - Networking at the Protein Society symposium.
AB  - From the complex behavior of multicomponent signaling networks to the structures
      of large protein complexes and aggregates, questions once viewed as daunting are
      now being tackled fearlessly by protein scientists. The 19th Annual Symposium of
      the Protein Society in Boston highlighted the maturation of systems biology as
      applied to proteins.

PMID- 16408048
TI  - Decoding chemical structures from genomes.

PMID- 16408050
TI  - Lox and Cre sandwich.

PMID- 16408049
TI  - Nitrite as an intrinsic signaling molecule.

PMID- 16408051
TI  - Targeted antioxidant delivery prolongs sperm lifespan.

PMID- 16408053
TI  - Mass spectrometry-based proteomics turns quantitative.
AB  - The field of proteomics is built on technologies to analyze large numbers of
      proteins--ideally the entire proteome--in the same experiment. Mass spectrometry
      (MS) has been successfully used to characterize proteins in complex mixtures, but
      results so far have largely been qualitative. Two recently developed
      methodologies offer the opportunity to obtain quantitative proteomic information.
      Comparing the signals from the same peptide under different conditions yields a
      rough estimate of relative protein abundance between two proteomes.
      Alternatively, and more accurately, peptides are labeled with stable isotopes,
      introducing a predictable mass difference between peptides from two experimental
      conditions. Stable isotope labels can be incorporated 'post-harvest', by chemical
      approaches or in live cells through metabolic incorporation. This isotopic handle
      facilitates direct quantification from the mass spectra. Using these quantitative
      approaches, precise functional information as well as temporal changes in the
      proteome can be captured by MS.

PMID- 16408054
TI  - High-throughput assay for small molecules that modulate zebrafish embryonic heart
      rate.
AB  - To increase the facility and throughput of scoring phenotypic traits in embryonic
      zebrafish, we developed an automated micro-well assay for heart rate using
      automated fluorescence microscopy of transgenic embryos expressing green
      fluorescent protein in myocardium. The assay measures heart rates efficiently and
      accurately over a large linear dynamic range, and it rapidly characterizes dose
      dependence and kinetics of small molecule-induced changes in heart rate. This is
      the first high-throughput micro-well assay for organ function in an intact
      vertebrate.

PMID- 16408055
TI  - Discovery of a new peptide natural product by Streptomyces coelicolor genome
      mining.
AB  - Analyses of microbial genome sequences reveal numerous examples of gene clusters
      encoding proteins typically involved in complex natural product biosynthesis but
      not associated with the production of known natural products. In Streptomyces
      coelicolor M145 there are several gene clusters encoding new nonribosomal peptide
      synthetase (NRPS) systems not associated with known metabolites. Application of
      structure-based models for substrate recognition by NRPS adenylation domains
      predicts the amino acids incorporated into the putative peptide products of these
      systems, but the accuracy of these predictions is untested. Here we report the
      isolation and structure determination of the new tris-hydroxamate tetrapeptide
      iron chelator coelichelin from S. coelicolor using a genome mining approach
      guided by substrate predictions for the trimodular NRPS CchH, and we show that
      this enzyme, which lacks a C-terminal thioesterase domain, together with a
      homolog of enterobactin esterase (CchJ), are required for coelichelin
      biosynthesis. These results demonstrate that accurate prediction of adenylation
      domain substrate selectivity is possible and raise intriguing mechanistic
      questions regarding the assembly of a tetrapeptide by a trimodular NRPS.

PMID- 16408056
TI  - A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa
      and enhances fertility.
AB  - Gamete-gamete interactions are critically modulated by carbohydrate-protein
      interactions that rely on the carbohydrate-selective recognition of polyvalent
      carbohydrate structures. A galactose-binding protein has been identified in
      mammalian spermatozoa that has similarity to the well-characterized hepatic
      asialoglycoprotein receptor. With the aim of exploiting the ability of this class
      of proteins to bind and internalize macromolecules displaying galactose, we
      designed hybrid carbohydrate-antioxidant polymers to deliver antioxidant vitamin
      E (alpha-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one
      hybrid polymer in particular produced large increases in intracellular sperm
      levels of alpha-tocopherol and greatly reduced endogenous fatty acid degradation
      under oxidative stress. The polymer-treated spermatozoa had enhanced
      physiological properties and longer half-lives, which resulted in enhanced
      fertilization rates. Our results indicate that hybrid polymer delivery systems
      can prolong the functional viability of mammalian spermatozoa and improve
      fertility rates, and that our functionally guided optimization strategy can be
      applied to the discovery of active glycoconjugate ligands.

PMID- 16408057
TI  - Preferential synapsis of loxP sites drives ordered strand exchange in Cre-loxP
      site-specific recombination.
AB  - The bacteriophage P1 Cre recombinase catalyzes site-specific recombination
      between 34-base-pair loxP sequences in a variety of topological contexts. This
      reaction is widely used to manipulate DNA molecules in applications ranging from
      benchtop cloning to genome modifications in transgenic animals. Despite the
      simple, highly symmetric nature of the Cre-loxP system, there is strong evidence
      that the reaction is asymmetric; the 'bottom' strands in the recombining loxP
      sites are preferentially exchanged before the 'top' strands. Here, we address the
      mechanistic basis for ordered strand exchange in the Cre-loxP recombination
      pathway. Using suicide substrates containing 5'-bridging phosphorothioate
      linkages at both cleavage sites, fluorescence resonance energy transfer between
      synapsed loxP sites and a Cre mutant that can cleave the bridging
      phosphorothioate linkage but not a normal phosphodiester linkage, we showed that
      preferential formation of a specific synaptic complex between loxP sites imposes
      ordered strand exchange during recombination and that synapsis stimulates
      cleavage of loxP sites.

PMID- 16408058
TI  - Neuronal synapse interaction reconstituted between live cells and supported lipid
      bilayers.
AB  - In the nervous system, homophilic and heterophilic adhesion molecules participate
      in the induction and differentiation of presynaptic transmitter release sites. We
      focus on the heterophilic interaction between postsynaptic neuroligin-1 (Nlg) and
      presynaptic beta-neurexin (Nrx). Nlg has previously been shown to trigger
      presynaptic differentiation in a Nrx-expressing axon even when presented on a non
      neuronal cell or on beads coated with lipid bilayers. We have now developed a new
      method to measure single molecule and ensemble distribution of Nrx and Nlg at the
      contact site between a non-neuronal Nrx-expressing cell and a flat supported
      glycosylphosphoinositol-neuroligin-1 (GPI-Nlg) lipid bilayer and relate them to
      adhesion as measured by cell migration and gravity dissociation. We find that
      within minutes after cell-bilayer contact, Nrx accumulates at the contact site
      and the contact area is expanded. The strength of cell-bilayer adhesion depends
      on the morphology of Nrx accumulation, with the focal concentration strengthening
      adhesion. The results suggest that Nlg-Nrx interaction rapidly establishes a
      weak, but specific, adhesion between dynamic pre- and postsynaptic processes,
      which may ultimately require additional molecules for synapse stabilization.

PMID- 16408062
TI  - Chemical biology at the crossroads of molecular structure and mechanism.
AB  - Chemical insight into biological function is the holy grail of structural
      biology. Small molecules are central players as building blocks, effectors and
      probes of macromolecular structure and function.

PMID- 16408059
TI  - Nitrite is a signaling molecule and regulator of gene expression in mammalian
      tissues.
AB  - Mammalian tissues produce nitric oxide (NO) to modify proteins at heme and
      sulfhydryl sites, thereby regulating vital cell functions. The majority of NO
      produced is widely assumed to be neutralized into supposedly inert oxidation
      products including nitrite (NO2(-)). Here we show that nitrite, also ubiquitous
      in dietary sources, is remarkably efficient at modifying the same protein sites,
      and that physiological nitrite concentrations account for the basal levels of
      these modifications in vivo. We further find that nitrite readily affects cyclic
      GMP production, cytochrome P450 activities, and heat shock protein 70 and heme
      oxygenase-1 expression in a variety of tissues. These cellular activities of
      nitrite, combined with its stability and abundance in vivo, suggest that this
      anion has a distinct and important signaling role in mammalian biology, perhaps
      by serving as an endocrine messenger and synchronizing agent. Thus, nitrite
      homeostasis may be of great importance to NO biology.

PMID- 16408063
TI  - Programming cellular function.
AB  - The process of cellular engineering is rapidly accelerating owing to advances in
      technologies to manipulate DNA and other biomolecules, giving rise to the field
      of synthetic biology. A meeting was held in August 2005 to present progress in
      the field and to discuss topics in ethics, safety and security.

PMID- 16408064
TI  - The emerging biology of the nitrite anion.
AB  - Nitrite has now been proposed to play an important physiological role in
      signaling, blood flow regulation and hypoxic nitric oxide homeostasis. A recent
      two-day symposium at the US National Institutes of Health highlighted recent
      advances in the understanding of nitrite biochemistry, physiology and
      therapeutics.

PMID- 16408065
TI  - Chemical cues for sea lamprey migration.

PMID- 16408066
TI  - New light on an open-and-shut case.

PMID- 16408067
TI  - Molecular motors: rocking and rolling.

PMID- 16408068
TI  - Interrupters on the bacterial party line.

PMID- 16408070
TI  - Mixture of new sulfated steroids functions as a migratory pheromone in the sea
      lamprey.
AB  - The sea lamprey is an ancient, parasitic fish that invaded the Great Lakes a
      century ago, where it triggered the collapse of many fisheries. Like many fishes,
      this species relies on chemical cues to mediate key aspects of its life,
      including migration and reproduction. Here we report the discovery of a
      multicomponent steroidal pheromone that is released by stream-dwelling larval
      lamprey and guides adults to spawning streams. We isolated three compounds with
      pheromonal activity (in submilligram quantities from 8,000 l of larval holding
      water) and deduced their structures. The most important compound contains an
      unprecedented 1-(3-aminopropyl)pyrrolidin-2-one subunit and is related to
      squalamine, an antibiotic produced by sharks. We verified its structure by
      chemical synthesis; it attracts adult lamprey at very low (subpicomolar)
      concentrations. The second component is another new sulfated steroid and the
      third is petromyzonol sulfate, a known lamprey-specific bile acid derivative.
      This mixture is the first migratory pheromone identified in a vertebrate and is
      being investigated for use in lamprey control.

PMID- 16408071
TI  - Evolution of glutamate interactions during binding to a glutamate receptor.
AB  - Glutamate receptors are the predominant mediators of excitatory synaptic signals
      in the central nervous system and are important in learning and memory as well as
      in diverse neuropathologies including epilepsy and ischemia. Their primary
      function is to receive the chemical signal glutamate (1), which binds to an
      extracellular domain in the receptor, and convert it into an electrical signal
      through the formation of cation-permeable transmembrane channels. Recently
      described end-state apo and ligated structures of the ligand-binding domain of a
      rat glutamate receptor provide a first view of specific molecular interactions
      between the ligand and the receptor that are central to the allosteric regulation
      of function in this protein. Yet there is little information on the mechanism and
      the structures of intermediates (if any) formed during the ligand-binding
      process. Here we have used time-resolved vibrational spectroscopy to show that
      the process involves a sequence of interleaved ligand and protein changes that
      starts with the docking of glutamate at the alpha-carboxylate moiety and ends
      with the establishment of the interactions between the gamma-carboxylate of
      glutamate and the protein.

PMID- 16408072
TI  - Host sphingolipid biosynthesis as a target for hepatitis C virus therapy.
AB  - An estimated 170 million individuals worldwide are infected with hepatitis C
      virus (HCV), a serious cause of chronic liver disease. Current interferon-based
      therapy for treating HCV infection has an unsatisfactory cure rate, and the
      development of more efficient drugs is needed. During the early stages of HCV
      infections, various host genes are differentially regulated, and it is possible
      that inhibition of host proteins affords a therapeutic strategy for treatment of
      HCV infection. Using an HCV subgenomic replicon cell culture system, here we have
      identified, from a secondary fungal metabolite, a lipophilic long-chain base
      compound, NA255 (1), a previously unknown small-molecule HCV replication
      inhibitor. NA255 prevents the de novo synthesis of sphingolipids, major lipid
      raft components, thereby inhibiting serine palmitoyltransferase, and it disrupts
      the association among HCV nonstructural (NS) viral proteins on the lipid rafts.
      Furthermore, we found that NS5B protein has a sphingolipid-binding motif in its
      molecular structure and that the domain was able to directly interact with
      sphingomyelin. Thus, NA255 is a new anti-HCV replication inhibitor that targets
      host lipid rafts, suggesting that inhibition of sphingolipid metabolism may
      provide a new therapeutic strategy for treatment of HCV infection.

PMID- 16408073
TI  - A torque component in the kinesin-1 power stroke.
AB  - Kinesin-1 is a twin-headed molecular motor that moves along microtubules in 8-nm
      steps, using a walking action in which the two heads interact alternately with
      the microtubule. Constructs with only one head can also produce impulses of force
      and motion, indicating that the walking action is an amplification strategy that
      leverages an underlying force-generating event. Recent work suggests that
      directional force is produced either by directionally biased selection of
      microtubule binding sites or by a conformational change subsequent to the binding
      event. We report here that surface-attached rat kinesin-1 monomers drive
      counterclockwise rotation of sliding microtubules around their axes, and that by
      manipulating the assay geometry, we could reduce or block the torsional motion
      with negligible effects on the axial motion. We can account for this behavior on
      the simple assumption that kinesin heads tend to bind to the closest available
      tubulin heterodimer in the lattice, but only in the case where an additional
      biasing process is present that shifts the start position for diffusion-to
      capture toward the microtubule plus end by approximately 1 nm.

PMID- 16408074
TI  - Entropy rectifies the Brownian steps of kinesin.
AB  - Kinesin is a stepping motor that successively produces forward and backward 8-nm
      steps along microtubules. Under physiological conditions, the steps powering
      kinesin's motility are biased in one direction and drive various biological
      motile processes. The physical mechanism underlying the unidirectional bias of
      the kinesin steps is not fully understood. Here we explored the mechanical
      kinetics and thermodynamics of forward and backward kinesin steps by analyzing
      their temperature and load dependence. Results show that the frequency asymmetry
      between forward and backward steps is produced by entropy. Furthermore, the
      magnitude of the entropic asymmetry is 6 k(B)T, more than three times greater
      than expected from a current model, in which a mechanical conformational change
      within the kinesin molecular structure directly biases the kinesin steps forward.
      We propose that the stepping direction of kinesin is preferably caused by an
      entropy asymmetry resulting from the compatibility between the kinesin and
      microtubule interaction based on their polar structures.

PMID- 16408078
TI  - Rights for students expanding.

PMID- 16408079
TI  - The origins of chemical biology.

PMID- 16408080
TI  - Preventing protein secretion with chemical glue.

PMID- 16408081
TI  - Chemical expansion of cofactor activity.

PMID- 16408082
TI  - Agonizing hedgehog.

PMID- 16408083
TI  - Ion channels get flashy.

PMID- 16408084
TI  - Opening the pore hinges on proline.

PMID- 16408085
TI  - Breaking and entering.

PMID- 16408087
TI  - Unraveling cell division mechanisms with small-molecule inhibitors.
AB  - Cell division is the process by which a cell creates two genetically identical
      daughter cells. To maintain genomic integrity, a complex and highly regulated
      sequence of events ensures that the replicated chromosomes are equally
      partitioned between the daughter cells. For more than 50 years, strategies
      designed around small-molecule inhibitors have been critical in advancing our
      understanding of this essential process. Here we introduce a series of questions
      on the biology of cell division and illustrate how small molecules have been used
      to design experiments to address these questions. Because of the highly dynamic
      nature of cell division, the temporal control over protein function that is
      possible with small molecules has been particularly valuable in dissecting
      biological mechanisms.

PMID- 16408088
TI  - Purmorphamine activates the Hedgehog pathway by targeting Smoothened.
AB  - Hedgehog (Hh) signaling is an important regulator of embryonic patterning, tissue
      regeneration, stem cell renewal and cancer growth. A purine derivative named
      purmorphamine was previously found to activate the Hh pathway and affect
      osteoblast differentiation through an unknown mechanism. We demonstrate here that
      purmorphamine directly targets Smoothened, a critical component of the Hh
      signaling pathway.

PMID- 16408089
TI  - Direct transfer of extended groups from synthetic cofactors by DNA
      methyltransferases.
AB  - S-Adenosyl-L-methionine (AdoMet) is the major methyl donor for biological
      methylation reactions catalyzed by methyltransferases. We report the first
      chemical synthesis of AdoMet analogs with extended carbon chains replacing the
      methyl group and their evaluation as cofactors for all three classes of DNA
      methyltransferases. Extended groups containing a double or triple bond in the
      beta position to the sulfonium center were transferred onto DNA in a catalytic
      and sequence-specific manner, demonstrating a high utility of such synthetic
      cofactors for targeted functionalization of biopolymers.

PMID- 16408090
TI  - Actin microfilament aggregation induced by withaferin A is mediated by annexin
      II.
AB  - The actin cytoskeleton supports diverse cellular processes such as endocytosis,
      oriented growth, adhesion and migration. The dynamic nature of the cytoskeleton,
      however, has made it difficult to define the roles of the many accessory
      molecules that modulate actin organization, especially the multifunctional
      adapter protein annexin II. We now report that the compound withaferin A (1) can
      alter cytoskeletal architecture in a previously unknown manner by covalently
      binding annexin II and stimulating its basal F-actin cross-linking activity. Drug
      mediated disruption of F-actin organization is dependent on annexin II expression
      by cells and markedly limits their migratory and invasive capabilities at
      subcytotoxic concentrations. Given the extensive ethnobotanical history of
      withaferin-containing plant preparations in the treatment of cancer and
      inflammatory and neurological disorders, we suggest that annexin II represents a
      feasible, previously unexploited target for therapeutic intervention by small
      molecule drugs.

PMID- 16408091
TI  - Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in
      vitro.
AB  - Inspired by the usefulness of small molecules to study membrane traffic, we used
      high-throughput synthesis and phenotypic screening to discover secramine, a
      molecule that inhibits membrane traffic out of the Golgi apparatus by an unknown
      mechanism. We report here that secramine inhibits activation of the Rho GTPase
      Cdc42, a protein involved in membrane traffic, by a mechanism dependent upon the
      guanine dissociation inhibitor RhoGDI. RhoGDI binds Cdc42 and antagonizes its
      membrane association, nucleotide exchange and effector binding. In vitro,
      secramine inhibits Cdc42 binding to membranes, GTP and effectors in a RhoGDI
      dependent manner. In cells, secramine mimics the effects of dominant-negative
      Cdc42 expression on protein export from the Golgi and on Golgi polarization in
      migrating cells. RhoGDI-dependent Cdc42 inhibition by secramine illustrates a new
      way to inhibit Rho GTPases with small molecules and provides a new means to study
      Cdc42, RhoGDI and the cellular processes they mediate.

PMID- 16408092
TI  - Allosteric control of an ionotropic glutamate receptor with an optical switch.
AB  - The precise regulation of protein activity is fundamental to life. The allosteric
      control of an active site by a remote regulatory binding site is a mechanism of
      regulation found across protein classes, from enzymes to motors to signaling
      proteins. We describe a general approach for manipulating allosteric control
      using synthetic optical switches. Our strategy is exemplified by a ligand-gated
      ion channel of central importance in neuroscience, the ionotropic glutamate
      receptor (iGluR). Using structure-based design, we have modified its ubiquitous
      clamshell-type ligand-binding domain to develop a light-activated channel, which
      we call LiGluR. An agonist is covalently tethered to the protein through an
      azobenzene moiety, which functions as the optical switch. The agonist is
      reversibly presented to the binding site upon photoisomerization, initiating
      clamshell domain closure and concomitant channel gating. Photoswitching occurs on
      a millisecond timescale, with channel conductances that reflect the
      photostationary state of the azobenzene at a given wavelength. Our device has
      potential uses not only in biology but also in bioelectronics and nanotechnology.

PMID- 16408093
TI  - ATM variants and predisposition to childhood T-lineage acute lymphoblastic
      leukaemia.

PMID- 16408095
TI  - CD49d in B-cell chronic lymphocytic leukemia: correlated expression with CD38 and
      prognostic relevance.

PMID- 16408096
TI  - JAK2 V617F mutation in classic chronic myeloproliferative diseases: a report on a
      series of 349 patients.

PMID- 16408097
TI  - Reduced-intensity conditioning allogeneic transplantation is associated with a
      high incidence of extramedullary relapses in multiple myeloma patients.

PMID- 16408098
TI  - JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative
      disorders.
AB  - A mutation in the JH2 pseudokinase domain of the Janus kinase 2 gene (JAK2 V617F)
      has been described in chronic myeloproliferative disorders (MPD). We screened 79
      acute myeloid leukemia (AML) cell lines and found five positive for JAK2 V617F
      (HEL, MB-02, MUTZ-8, SET-2, UKE-1), 4/5 with histories of MPD/MDS. While SET-2
      expressed both mutant (mu) and wild-type (wt) JAK2, remaining positives carried
      homo-/hemizygous JAK2 mutations. Microsatellite analysis confirmed losses of
      heterozygosity (LOH) affecting the JAK2 region on chromosome 9p in MB-02, MUTZ-8
      and UKE-1, but also in HEL, the only JAK2mu cell line lacking any reported
      MPD/MDS history. All five JAK2mu cell lines displayed cytogenetic hallmarks of
      MDS, namely losses of 5q or 7q, remarkably in 4/5 cases affecting both
      chromosomes. Our combined FISH and microsatellite analysis uncovered a novel
      mechanism to supplement mitotic recombination previously proposed to explain JAK2
      LOH, namely chromosome deletion with/without selective JAK2mu amplification.
      Confirming the importance of the mutated JAK2 protein for growth and prevention
      of apoptosis, JAK2mu cell lines displayed higher sensitivities to JAK2 inhibition
      than JAK2wt cell lines. In summary, JAK2 V617F cell lines, derived from patients
      with history of MPD/MDS, represent novel research tools for elucidating the
      pathobiology of this JAK2 mutation.

PMID- 16408099
TI  - Cytolytic function and survival of natural killer cells are severely altered in
      myelodysplastic syndromes.
AB  - Natural Killer (NK) cells are critical in host defense against malignant
      transformation and are potent antileukemic cytotoxic effectors. In the present
      study, we investigated the peripheral NK function in patients with
      myelodysplastic syndromes (MDS). We demonstrated that the peripheral NK cell
      population was quantitatively normal in MDS patients. Furthermore, NK cells
      displayed an expression of the activating natural cytotoxicity receptors (NCR)
      NKp46 and NKp30 as well as NKG2D similar to that observed in donors, but exert a
      highly decreased constitutive cytolytic activity compared to resting normal NK
      cells. Although activation with IL-2 resulted in the upregulation of NKp46
      expression by MDS-NK cells, their cytolytic function remained deeply altered as
      compared to activated donor NK cells. In addition, MDS NK cells did not
      proliferate in vitro, and displayed an increased rate of apoptosis in response to
      IL-2 stimulation although the spontaneous apoptosis was not significantly
      increased. Interestingly, a proportion of peripheral MDS-NK cells were derived
      from the MDS clone as the cytogenetic anomaly found in bone marrow karyotype was
      also detected in 20-50% of circulating NK cells. In conclusion, NK cells'
      cytolytic function and proliferative capacities in response to activation by
      cytokines are profoundly altered in MDS.

PMID- 16408100
TI  - Increase of CCR7- CD45RA+ CD8 T cells (T(EMRA)) in chronic graft-versus-host
      disease.

PMID- 16408101
TI  - High Mda-7 expression promotes malignant cell survival and p38 MAP kinase
      activation in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL)-B-cells are quiescent differentiated cells
      that produce interleukin (IL)-10 and accumulate due to resistance to apoptosis.
      The mechanisms underlying such resistance are poorly understood. Herein we show
      that all CLL B-cells tested (30/30) display high mRNA and protein expression of
      the tumor suppressor Mda-7/IL-24, an IL-10 family member, in comparison to normal
      B cells. A downstream Mda-7 signaling target, p38 mitogen-activated protein
      kinase (MAPK) was highly phosphorylated in all CLL cells but not in normal B
      cells. Mda-7 expression and p38 MAPK phosphorylation diminished in culture and
      the latter could be reinduced by recombinant (r)-IL-24 or LPS and Mda-7
      transfection. Mda-7/IL-24 siRNA specifically inhibited p38 MAPK phosphorylation
      in CLL without affecting p38 MAPK, bcl2, or Lyn expression, further demonstrating
      the direct role of Mda-7/IL-24 in p38 MAPK activation. Both pharmacological
      inhibition of p38 MAPK and Mda-7 silencing augmented spontaneous apoptosis by
      three-fold in CLL cells cultured in autologous serum, which was reversed by LPS
      and r-IL-24. We established the role of p38 MAPK in CLL cell survival and
      demonstrated a paradoxical effect, whereby Mda-7 and IL-24, inducers of apoptosis
      in diverse cancer cells, promote the survival of CLL B-cells through p38 MAPK
      activation.

PMID- 16408102
TI  - Combination of broad molecular screening and cytogenetic analysis for genetic
      risk assignment and diagnosis in patients with acute leukemia.
AB  - We evaluated the impact of genetic analysis combining cytogenetics and broad
      molecular screening on leukemia diagnosis according to World Health Organization
      (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay
      was used that allowed the detection of 29 fusion transcripts. A total of 186
      patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31
      ALL (17%)) characterized by morphology and immunophenotyping were included. Of
      these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing
      revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis
      revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were
      genetically classified as favorable, 107 (58%) intermediate and 52 (28%)
      unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk
      assignments obtained from broad molecular screening and cytogenetics. Cryptic
      fusion transcripts in nine (5%) patients changed the genetic risk assignment in
      four and the WHO classification in four patients. In 34 patients (18%),
      cytogenetics defined the risk assignment by revealing structural and numerical
      chromosomal abnormalities not detected by molecular screening. Broad molecular
      screening and cytogenetics are complementary in the diagnosis and genetic risk
      assignment of acute leukemia.

PMID- 16408103
TI  - Aortic stiffness in children of parents with hypertension.

PMID- 16408104
TI  - The early days of nephrology in Colombia.

PMID- 16408105
TI  - Acute oxalate nephropathy due to ethylene glycol ingestion.

PMID- 16408106
TI  - Homocysteine and risk in end-stage renal disease: a matter of context.
AB  - Like blood pressure and cholesterol, homocysteine shows a paradoxical inverse
      relationship with cardiovascular complications in end-stage renal disease (ESRD).
      A paper by Ducloux et al. in this issue adds perhaps decisive evidence on
      malnutrition-hypoalbuminemia as the main factor explaining the counterintuitive
      association between homocysteine and clinical outcome reported in previous
      studies.

PMID- 16408107
TI  - Inflammation and dyslipidemia in nephropathy: an epidemiologic perspective.
AB  - The association of dyslipidemia and inflammatory markers with decreased renal
      function has been reported in several large epidemiologic studies. In this issue,
      Lin et al examine these associations among middle-aged and older type 2 diabetes,
      a population at high risk for chronic kidney disease. Their findings support a
      role for these factors in the pathogenesis of progressive renal disease.

PMID- 16408108
TI  - Renal fibrosis: new insights into the pathogenesis and therapeutics.
AB  - Renal fibrosis is the inevitable consequence of an excessive accumulation of
      extracellular matrix that occurs in virtually every type of chronic kidney
      disease. The pathogenesis of renal fibrosis is a progressive process that
      ultimately leads to end-stage renal failure, a devastating disorder that requires
      dialysis or kidney transplantation. In a simplistic view, renal fibrosis
      represents a failed wound-healing process of the kidney tissue after chronic,
      sustained injury. Several cellular pathways, including mesangial and fibroblast
      activation as well as tubular epithelial-mesenchymal transition, have been
      identified as the major avenues for the generation of the matrix-producing cells
      in diseased conditions. Among the many fibrogenic factors that regulate renal
      fibrotic process, transforming growth factor-beta (TGF-beta) is one that plays a
      central role. Although defective matrix degradation may contribute to tissue
      scarring, the exact action and mechanisms of the matrix-degrading enzymes in the
      injured kidney have become increasingly complicated. Recent discoveries on
      endogenous antifibrotic factors have evolved novel strategies aimed at
      antagonizing the fibrogenic action of TGF-beta/Smad signaling. Many therapeutic
      interventions appear effective in animal models; however, translation of these
      promising results into humans in the clinical setting remains a daunting task.
      This mini-review attempts to highlight the recent progress in our understanding
      of the cellular and molecular pathways leading to renal fibrosis, and discusses
      the challenges and opportunities in developing therapeutic strategies.

PMID- 16408109
TI  - New insights into mineral and skeletal regulation by active forms of vitamin D.
AB  - Recent studies in mice using genetic approaches have shed new light on the
      physiological effects of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and the vitamin D
      receptor (VDR) in skeletal and mineral homeostasis, and on their interaction with
      calcium. These studies in mice with targeted deletion of the 25-hydroxyvitamin D
      1alpha-hydroxylase (1alpha(OH)ase), and of the VDR or of double mutants, have
      shown the discrete effects of calcium in inhibiting parathyroid hormone secretion
      and in enhancing bone mineralization, but overlapping effects of calcium and
      1,25(OH)(2)D on inhibiting parathyroid growth and on normal development of the
      cartilaginous growth plate. The 1,25(OH)(2)D/VDR system is essential, however, in
      enhancing intestinal calcium absorption and in optimally increasing osteoclastic
      activation. In addition, the 1,25(OH)(2)D/VDR system has important anabolic
      effects on bone, thus defining a dual role for this system in bone turnover.
      These studies are revealing functions of the vitamin D/VDR system which have
      relevance for new concepts of the pathophysiology of renal bone disease and, in
      particular, of the adynamic bone disorder, and for the development of new analogs
      of the active form of vitamin D, which have less calcemic activity and greater
      skeletal anabolic effects.

PMID- 16408110
TI  - Kidney cancer: identification of novel targets for therapy.
AB  - Kidney cancer, although relatively rare when compared to other malignancies,
      occurs not uncommonly in patients with renal disease and is often discovered
      incidentally during the initial nephrologic work-up, or by the savvy clinician
      who is familiar with the paraneoplastic signs. While surgical approaches are
      generally curative when the disease is confined to the kidney, one-third of the
      cases that present in the metastatic form and require conventional medical
      therapy are associated with a truly dismal patient survival rate. In light of the
      emerging knowledge of the molecular mechanisms of kidney cancer oncogenesis,
      several novel and promising therapeutic approaches are emerging. In this review,
      we summarize the current state of kidney cancer diagnosis and therapy, as well as
      some of the novel treatments that capitalize on those newly elucidated molecular
      pathways that are deranged in this disease.

PMID- 16408111
TI  - Role of the T-cell receptor in kidney ischemia-reperfusion injury.
AB  - T cells have been demonstrated to modulate ischemia-reperfusion injury (IRI) in
      kidney, lung, liver and intestine. The underlying mechanisms for T-cell
      engagement in IRI are unknown. We hypothesized that the T-cell receptor (TCR)
      plays a role in renal IRI, and examined the effects of TCR alpha/beta (alphabeta)
      and gamma/delta (gammadelta) deficiency on ischemic acute renal failure (ARF).
      TCR-specific deficiency in specific mice was confirmed by fluorescence-activated
      cell sorting analysis using monoclonal antibodies (Abs). IRI was induced by
      bilateral clamping of kidney pedicles for 30 min, followed by reperfusion. Serum
      creatinine and kidney histopathology were used to assess the severity of
      experimental ARF. TCR alphabeta-deficient mice were significantly protected from
      kidney dysfunction compared to wild-type (WT) littermates after IRI (P<0.05).
      Histologic analysis demonstrated a significant reduction in renal tubular injury
      in both TCR alphabeta- and gammadelta-deficient mice compared to WT mice
      postischemia. TCR alphabeta-deficient mice had reduced tumor necrosis factor
      alpha and interleukin-6 protein expression in kidney tissue compared to WT mice
      at 24 h postischemia using a microbead-based protein detection platform. Relative
      protection from kidney IRI did not correlate with neutrophil and macrophage
      infiltration of kidney tissue. Thus, the TCR plays a direct but modest
      pathophysiological role in kidney IRI. These data suggest that alloantigen
      independent activation in IRI can lead to engagement of antigen-specific
      molecules on T cells. Furthermore, given that the TCR is already a target for
      diagnostics and therapeutic strategies in immune diseases, these approaches can
      now be harnessed for IRI.

PMID- 16408112
TI  - Treatment with CO-RMs during cold storage improves renal function at reperfusion.
AB  - Low concentrations of carbon monoxide (CO) can protect tissues against ischemia
      reperfusion (I-R) injury. We have recently identified a novel class of compounds,
      CO-releasing molecules (CO-RMs), which exert important pharmacological activities
      by carrying and delivering CO to biological systems. Here, we examined the
      possible beneficial effects of CO liberated from CO-RMs on the damage inflicted
      by cold storage and I-R in isolated perfused kidneys. Hemodynamic and biochemical
      parameters as well as mitochondrial respiration were measured in isolated
      perfused rabbit kidneys that were previously flushed with CO-RMs and stored at 4
      degrees C for 24 h. Two water-soluble CO-RMs were tested: (1) sodium
      boranocarbonate (CORM-A1), a boron-containing carbonate that releases CO at a
      slow rate, and (2) tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), a
      transition metal carbonyl that liberates CO very rapidly in solution. Kidneys
      flushed with Celsior solution supplemented with CO-RMs (50 microM) and stored at
      4 degrees C for 24 h displayed at reperfusion a significantly higher perfusion
      flow rate (PFR), glomerular filtration rate, and sodium and glucose reabsorption
      rates compared to control kidneys flushed with Celsior solution alone. Addition
      of 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), a guanylate cyclase
      inhibitor, prevented the increase in PFR mediated by CO-RMs. The respiratory
      control index from kidney mitochondria treated with CO-RMs was also markedly
      increased. Notably, renal protection was lost when kidneys were flushed with
      Celsior containing an inactive compound (iCO-RM), which had been deliberately
      depleted of CO. CO-RMs are effective therapeutic agents that deliver CO during
      kidney cold preservation and can be used to ameliorate vascular activity, energy
      metabolism and renal function at reperfusion.

PMID- 16408113
TI  - Lipoxin A4 inhibits connective tissue growth factor-induced production of
      chemokines in rat mesangial cells.
AB  - Connective tissue growth factor (CTGF) is involved in mitogenesis, matrix
      production, and chemotaxis in mesenchymal cells. The effects of CTGF on the
      production of chemokines remain unclear. The present studies investigate the
      regulatory role of CTGF in the production of fractalkine, monocyte
      chemoattractant protein-1 (MCP-1), and RANTES (regulated upon activation, normal
      T cell expressed and secreted) in cultured mesangial cells of rats, and the
      modulatory effects of lipoxin A(4) (LXA(4)) on actions of CTGF. CTGF enhanced the
      mRNA expression and protein release of fractalkine, MCP-1, and RANTES, the
      expression of phospho (P)-p42/44 mitogen-activated protein kinase (MAPK), P
      phosphoinositide 3-kinase (PI3-K), P-Akt, and activity of nuclear factor-kappaB
      (NF-kappaB) in mesangial cells. P-p42/44 MAPK blockade inhibited the CTGF-induced
      expression of P-p42/44 MAPK but not NF-kappaB, and partially decreased the levels
      of the above chemokines in supernatants. P-PI3-K blockade downregulated the CTGF
      stimulated expression of P-PI3-K, P-Akt, and NF-kappaB but not P-p42/44 MAPK, and
      partially decreased the release of the above chemokines. NF-kappaB blockade
      abrogated the CTGF-activated NF-kappaB and partially decreased the secretion of
      the above chemokines. LXA(4) dose-dependently inhibited the CTGF-stimulated mRNA
      expression and protein release of the above chemokines, and the expression of P
      p42/44MAPK, P-PI3-K, P-Akt, and NF-kappaB. In conclusion, these results
      demonstrate that CTGF induces production of fractalkine, MCP-1, and RANTES via
      the p42/44 MAPK-, PI3-K/Akt-, and NF-kappaB-dependent signal pathway, and LXA(4)
      downregulates the above effects of CTGF on rat mesangial cells.

PMID- 16408114
TI  - Butyrate modulates TGF-beta1 generation and function: potential renal benefit for
      Acacia(sen) SUPERGUM (gum arabic)?
AB  - Anecdotal evidence suggests that high fibre supplementation of dietary intake may
      have health benefits in renal disease related to alterations in circulating
      levels of short-chain fatty acids. The aim of the study was to examine the
      hypothesis that dietary manipulation may increase serum butyrate and thus have
      potential beneficial effects in renal disease. We examined the effect of dietary
      supplementation with a gum arabic sample of standardized molecular
      characteristics, Acacia(sen) SUPERGUM EM2 (SUPERGUM), on systemic levels of
      butyrate in normal human subjects. In an in vitro study, we also examined the
      potential role of butyrate in modifying the generation of the profibrotic
      cytokine transforming growth factor-beta (TGF-beta1) by renal epithelial cells.
      Following 8 weeks of dietary supplementation with 25 g/day of SUPERGUM, there was
      a two-fold increase in serum butyrate (n=7, P=0.03). In vitro work demonstrated
      that exposure of renal epithelial cells to elevated concentrations of butyrate
      suppressed both basal and stimulated TGF-beta1 synthesis. The action of butyrate
      was mediated by suppression of the extracellular signal-regulated kinase/mitogen
      activated protein kinase signalling pathway. In addition, butyrate exposures
      reduced the response of renal epithelial cells to TGF-beta1 as assessed by
      luciferase activity of a TGF-beta-responsive reporter construct. Attenuation of
      TGF-beta1 signalling was associated with reduced phosphorylation of Smad 3 and
      decreased trafficking of TGF-beta1 receptors into signalling, non-lipid raft
      associated membrane fractions. In conclusion, the data demonstrate that dietary
      supplementation with SUPERGU increased serum butyrate, which at least in vitro
      has beneficial effects on renal pro-fibrotic cytokine generation.

PMID- 16408115
TI  - Mild renal insufficiency is associated with reduced coronary flow in patients
      with non-obstructive coronary artery disease.
AB  - Patients with chronic kidney disease (CKD) have increased risk for cardiovascular
      events. However, the association between these pathophysiological processes is
      unclear. Therefore, this study was designed to determine the association between
      early CKD and coronary microvascular disease in patients with normal or mildly
      diseased coronary arteries. A total of 605 patients with normal or mildly
      diseased coronary arteries based on angiography underwent coronary flow reserve
      (CFR) evaluation using intracoronary adenosine. Patients were divided based on
      glomerular filtration rate (GFR). CKD was defined as calculated GFR<60
      ml/min/1.73 m(2). Patients with normal GFR (> or =60 ml/min/1.73 m(2), n=481) had
      higher CFR compared to those with CKD (n=124, CFR=3.0+/-0.8 vs 2.6+/-0.6,
      P<0.001, respectively). Patients with abnormal GFR were more likely to be older
      and of female gender, with greater prevalence of hypertension. Multiple logistic
      regression analysis adjusted for the aforementioned risk factors further
      supported the observed relationship. The current study shows that reduced renal
      function is associated with attenuated coronary vasodilator capacity in patients
      without obstructive coronary artery disease. The correlation between low GFR and
      reduced CFR may suggest parallel alterations in the renal and coronary
      microcirculation at the early stage of disease. Impairment in both
      microcirculatory beds may reflect an unmeasured risk factor induced by blunted
      renal function and add a burden to the increased propensity for cardiovascular
      events in CKD.

PMID- 16408116
TI  - Increased mesangial cell hyaluronan expression in lupus nephritis is mediated by
      anti-DNA antibody-induced IL-1beta.
AB  - The mechanism by which anti-DNA antibodies contribute to the pathogenesis of
      lupus nephritis (LN) remains to be fully elucidated. Hyaluronan (HA) is an
      important extracellular matrix constituent that accumulates during tissue injury,
      and participates in lymphocyte recruitment to sites of inflammation. The role of
      HA in the pathogenesis of LN has not been defined. We investigated the expression
      of HA in renal biopsies and circulating HA levels in patients with diffuse
      proliferative LN, and the effect of human anti-DNA antibodies on HA synthesis in
      cultured human mesangial cells (HMC). HA expression was increased in the
      mesangium, and in the periglomerular and tubular distribution in LN kidney
      biopsies. LN patients showed increased levels of circulating HA, especially
      during active disease, which correlated with anti-DNA antibody titers (r=0.35,
      P=0.0234). Anti-DNA antibodies isolated during active LN but not remission
      increased de novo synthesis of (3)H-labeled HA, which was accompanied by
      induction of HA synthase (HAS) II transcription, and enhanced IL-1beta, IL-6, and
      tumor necrosis factor-alpha secretion in HMC (P<0.001 for all). Only anti-DNA
      antibody induction of IL-1beta enhanced HA synthesis, which was abrogated by
      inhibitors of de novo mRNA or protein synthesis. Our findings demonstrate that HA
      expression is significantly increased within the mesangium in diffuse
      proliferative LN mediated through anti-DNA antibody-induced IL-1beta. Given that
      HA plays a pivotal role during inflammatory responses, influences cellular
      behavior and assists in the recruitment of lymphocytes to sites of injury, it is
      likely that HA contributes to the pathogenesis of LN.

PMID- 16408117
TI  - Gender-related differences in advanced glycation endproducts, oxidative stress
      markers and nitric oxide synthases in rats.
AB  - An age- and blood pressure-associated increase in methylglyoxal (MG) and MG
      induced advanced glycation endproducts (AGEs), including N(epsilon)-carboxyethyl
      lysine (CEL) and N(epsilon)-carboxymethyl-lysine (CML), in the kidney of
      spontaneously hypertensive rats (SHR) has been shown. In the present study,
      gender-related changes in AGEs and nitric oxide synthase were investigated in
      Sprague-Dawley (SD) and stroke-prone SHR (SHRsp) rats. Immunohistochemical
      analyses were conducted on kidneys from 24-week-old male and female SD rats as
      well as SHRsp. The systolic blood pressure of SHRsp was significantly higher than
      that of SD rats. Male SD rats had more intense kidney staining for CEL than
      female SD rats. Both male and female SHRsp had more marked CEL and CML staining
      localized to kidney tubules, as opposed to SD rats. Female rats showed more
      staining in glomerular vessels than male rats in both SD and SHRsp. Nuclei
      containing nuclear factor-kappaB (NF-kappaB) p65 and activated macrophages were
      seen in the kidney from SHRsp, not so much in SD rats, localized to renal tubules
      in male and glomerular vessels in female SHRsp. A higher protein level of NF
      kappaB p65 was found in SHRsp than in SD rats. SD rats had more intense kidney
      neuronal nitric oxide synthase staining than SHRsp. The intensity of inducible
      nitric oxide synthase staining was significantly higher in SHRsp than in SD rats,
      with no gender differences in either strain. SHRsp and male rats exhibited higher
      AGEs and oxidative stress than SD and female rats, respectively. These
      differences might partly account for the development of hypertension in SHRsp and
      the higher vulnerability of male animals to renal pathology.

PMID- 16408118
TI  - Involvement of de novo ceramide synthesis in radiocontrast-induced renal tubular
      cell injury.
AB  - We reported previously that various radiocontrast media cause apoptosis in
      porcine proximal tubular (LLC-PK(1)) cells, in which reduction in B-cell lymphoma
      (Bcl)-2 expression and caspase-3 activation are implicated. In the present study,
      we investigated a role for ceramide in radiocontrast media-induced apoptosis in
      renal tubular cells. LLC-PK(1) cells were exposed to radiocontrast media for 30
      min, followed by incubation for 24 h in normal medium. Cell viability was
      assessed by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)
      2H-tetrazolium monosodium salt assay, while apoptosis was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling stain.
      Immunofluorescent stains were performed using antibodies against phosphorylated
      Akt (pAkt) and cAMP response element binding protein (CREB) (pCREB), and
      ceramide. The mRNA expression and protein content of Bcl-2 were determined by
      reverse transcriptase-polymerase chain reaction and enzyme immunoassay,
      respectively. In vivo model of contrast-induced renal injury was induced in mice
      with unilateral renal occlusion. The cell injury induced by the nonionic
      radiocontrast medium ioversol was reversed by inhibiting de novo ceramide
      synthesis with fumonisin B(1) (FB(1)) and L-cycloserine, but not by suppressing
      sphingomyelin breakdown with D609. FB(1) reversed ioversol-induced decrease in
      the immunoreactivities of pAkt and pCREB, reduction in Bcl-2 expression and
      caspase-3 activation. Like ioversol, C2 ceramide and the Akt inhibitor Src
      homology-6 induced apoptosis by reducing pAkt and pCREB-like immunoreactivities,
      lowering Bcl-2 expression and enhancing caspase-3 activity. Indeed, various
      radiocontrast media, excluding iodixanol which showed the least nephrotoxicity,
      enhanced ceramide-like immunoreactivity. The role for de novo ceramide synthesis
      was also shown in the in vivo model of radiocontrast nephropathy. We demonstrated
      here for the first time that the enhancement of de novo ceramide synthesis
      contributes to radiocontrast nephropathy.

PMID- 16408119
TI  - Arginine uptake is attenuated through modulation of cationic amino-acid
      transporter-1, in uremic rats.
AB  - Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure
      (CRF). Defective nitric oxide (NO) generation due to decreased endothelial NO
      synthase (eNOS) activity is a crucial parameter characterizing ECD. L-arginine is
      the sole precursor for NO biosynthesis. Among several transporters that mediate L
      arginine uptake, cationic amino-acid transporter-1 (CAT-1) acts as the specific
      arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major
      determinant of eNOS activity in CRF. We studied glomerular and aortic arginine
      uptake, CAT-1, and CAT-2 messenger ribonucleic acid (mRNA) expression, and CAT-1
      protein in: (a) rats 6 weeks following 5/6 nephrectomy (CRF), (b) sham-operated
      animals, and (c) rats with CRF treated orally with either atorvastatin or
      arginine in drinking water (modalities which have been shown to enhance eNOS
      activity and improve endothelial function). Both glomerular and aortic arginine
      transport were significantly decreased in CRF. Treatment with either arginine or
      atorvastatin abolished the decrease in arginine uptake in CRF rats. Using reverse
      transcriptase-polymerase chain reaction and Northern blotting, we found a
      significant increase in glomerular and aortic CAT-1 mRNA expression in CRF.
      Western blotting revealed that CAT-1 protein was decreased in CRF, but remained
      intact following arginine and atorvastatin administration. Renal and systemic
      arginine uptake is attenuated in CRF, through modulation of CAT-1 protein. These
      findings provide a possible novel mechanism to eNOS inactivation and endothelial
      dysfunction in uremia.

PMID- 16408120
TI  - Renal ENaC subunit, Na-K-2Cl and Na-Cl cotransporter abundances in aged, water
      restricted F344 x Brown Norway rats.
AB  - Renal sodium reabsorption is a key determinant of final urine concentration. Our
      aim was to determine whether differences existed between aged and young rats in
      their response to water restriction with regard to the regulation of abundance of
      any of the major distal renal sodium transporter proteins. Male Fisher 344 x
      Brown Norway (F344 x BN) rats of 3-, 10-, 24-, or 31 months of age (3M, 10M, 24M,
      or 31M) were either water restricted (WR) for 5 days or control (ad libitum
      water). Major renal sodium transporters and channel subunits were evaluated by
      immunoblotting and immunohistochemistry. Age did not significantly affect plasma
      arginine vasopressin or aldosterone levels, but renin activity was only 8% in 31M
      WR rats relative to 3M-WR (P<0.05). Extreme aging (31M) led to decreased outer
      medullary abundance of the bumetanide-sensitive Na-K-2Cl cotransporter and
      decreased cortical abundance of the beta- and gamma-subunits (70-kDa band) of the
      epithelial sodium channel (ENaC) (P<0.05). Water restriction significantly
      (P<0.05) increased the abundance of Na-K-2Cl cotransporter (NKCC2) and Na-Cl
      cotransporter (NCC) across ages. However, these increases were significantly
      blunted as rats aged. Mean band densities were increased in WR rats (relative to
      age controls) by 54 and 106% at 3M, but only 25 and 29% at 24M and 0 and 6% at
      31M for NKCC2 and NCC, respectively. Aged F344 x BN rats have reduced basal
      distal tubular renal sodium transporter abundances and blunted upregulation
      during water restriction, which may contribute to decreased urinary concentrating
      capacity.

PMID- 16408121
TI  - Changes in the human peritoneal mesothelial cells during aging.
AB  - The number of older patients admitted to peritoneal dialysis (PD) programmes is
      growing. At the same time, there is increasing data about the role of mesothelial
      cells in determining the functional alteration of the peritoneum during PD.
      However, little is known about the functional changes accompanying the ageing
      process in mesothelial cells. We aimed to evaluate whether the aging process is
      accompanied by changes in some functional characteristic of the human peritoneal
      mesothelial cells (HPMC), which could account for the poor prognosis observed in
      old patients with PD. HPMCs were isolated from patients undergoing a nonurgent,
      nonseptic abdominal surgical procedure, without renal, vascular or inflammatory
      disease. Cytokine levels (by enzyme-linked immunosorbent assay (ELISA)),
      nitrates+nitrites, and cyclooxygenase (COX) activity (by a chemiluminescence
      assay), cytokines, COX, nitric oxide synthase (NOS), and nuclear factor (NF)
      kappaB1, two messenger ribonucleic acid (mRNA) gene expressions (by reverse
      transcriptase (RT)-Multiplex PCR), COX, and NOS promoter gene activities, and NF
      kappaB-dependent transcription (by transient transfection assays) were
      determined. Our data show a significant increase in cytokines, COX, and NOS
      activities, and mRNA expression of cytokines, COX-2, inducible nitric oxide
      synthase (iNOS) and precursors of NF-kappaB in HPMCs from old people. This was
      also the case for COX-2 and iNOS promoter gene activities and NF-kappaB-dependent
      transcription. There was a positive correlation between the age of the donor's
      cell and the proinflammatory profile of the HPMCs. Such age-dependent increase
      (around two-three times) is partially abolished by different antioxidant or free
      radical scavengers. Thus, aging is accompanied by the presence of an inflammatory
      state in HPMCs, which involves the participation of different reactive oxygen
      species.

PMID- 16408122
TI  - Bone marrow cell infusion ameliorates progressive glomerulosclerosis in an
      experimental rat model.
AB  - Bone marrow (BM) cells contribute to the maintenance and repair of several
      compartments of the kidney, including the endothelium, interstitium, epithelium,
      and the mesangium. The aim of this study was to explore the therapeutic use of
      bone marrow-derived cells (BMDC) that can differentiate into endothelial and
      mesangial cells in a model of progressive glomerulosclerosis. To investigate the
      involvement of BMDC in glomerular repair, progressive glomerulosclerosis was
      induced in enhanced green fluorescent protein BM chimeric rats by a one-shot
      injection of anti-Thy-1.1 monoclonal antibody, followed by unilateral
      nephrectomy. Subsequently, these rats were treated with either a BM cell infusion
      or phosphate-buffered saline. Renal function, intravital glomerular hemodynamics,
      and histological alterations were examined 12 weeks after anti-Thy-1.1 monoclonal
      antibody injection. Inflammatory infiltration of macrophages in the kidneys was
      evaluated by immunofluorescence of ED-1. We also determined whether BMDC
      contributed to repair and regeneration of endothelial and mesangial cells by
      immunofluorescence monitoring. As a result, BM cell infusion improved renal
      function and glomerular hemodynamics, and histological alterations with reduced
      glomerular infiltration of macrophages, leading to dramatically reduced mortality
      in this model of progressive glomerulosclerosis. We also demonstrated that, in
      the BM cell infusion group, more BMDC contributed to repair and regeneration of
      endothelial and mesangial cells than in the untreated group. The present study
      provides us with a conceptual basis for the development of therapeutic stem cell
      strategies aimed at enhancing recovery from progressive glomerulosclerosis.

PMID- 16408123
TI  - Impact of malnutrition-inflammation on the association between homocysteine and
      mortality.
AB  - Whether high total serum homocysteine levels (tHcy) contribute to increase
      mortality or offer a survival advantage in chronic hemodialysis patients remains
      controversial. We conducted a prospective study to determine the impact of tHcy
      on survival in this population with special respect to chronic inflammation
      malnutrition state (CIMS). In this prospective study, 459 hemodialysis patients
      from 10 dialysis centers located in two regions of France were included. A number
      of baseline parameters were measured including tHcy and markers of CIMS. Over a
      mean follow-up period of 54 months, 219 deaths (47.7%) occurred, of which 114
      (52%) were of cardiovascular (CV) origin. tHcy of equal to or greater than 30
      micromol/l was associated with a higher risk of all-cause mortality in patients
      without CIMS (hazard ratio (HR): 1.55 (confidence interval (CI): 1.12-4.72)), but
      not in overall dialysis population or those with CIMS. When only CV mortality was
      considered, tHcy of equal to or greater than 30 micromol/l was associated with a
      higher risk in patients without (CIMS HR: 1.91 (CI: 1.23-3.23)), but not in those
      with CIMS. Hyperhomocysteinemia is a strong risk factor for all-cause and CV
      mortality in hemodialysis patients who do not present CIMS. This association
      might be masked in patients with CIMS.

PMID- 16408125
TI  - Dialysis and kidney transplantation among patients living in rural areas of the
      United States.
AB  - Although one-fifth of the United States population is rural, little is known
      about the characteristics and outcomes of rural dialysis patients. We measured
      the association of rural residence with patient characteristics, survival, and
      time to transplant among 552,279 patients who initiated dialysis between January
      1, 1995 and December 31, 2002 and survived more than 90 days. We also examined
      the characteristics of 4363 Medicare-certified dialysis facilities by degree of
      rurality. Compared with urban patients, rural dialysis patients were older, less
      racially diverse with a higher prevalence of most co-morbid conditions.
      Hemodialysis was the dominant modality in both urban and rural areas, although
      the use of peritoneal dialysis was more frequent in rural areas. Survival and
      time to transplant differed by racial-ethnic group. Most notably, despite
      slightly better survival associated with rural vs urban residence among black
      populations, black populations living in rural areas were less likely to be
      transplanted than their urban counterparts (and than any other group examined).
      Compared with urban facilities, rural facilities are smaller, less likely to be
      for profit or owned by a large chain. Nonetheless, rural facilities perform at
      least as well as urban facilities based on standard performance measures. Despite
      more frequent use of peritoneal dialysis among rural patients, rural facilities
      were markedly less likely to offer peritoneal dialysis or home hemodialysis
      training than urban facilities. Rural black patients (most of whom live in the
      south) should be targeted in policies to reduce racial disparities in access to
      transplant. Further studies are needed to determine whether rural dialysis
      patients have adequate access to home-based therapies.

PMID- 16408124
TI  - The association of serum lipids and inflammatory biomarkers with renal function
      in men with type II diabetes mellitus.
AB  - Dyslipidemia and inflammation may promote renal disease via mechanisms of
      vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse
      data, however, are available on the relation of lipids and inflammatory
      biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a
      cross-sectional study of 732 men with type II DM enrolled in the Health
      Professionals' Follow-Up Study. Plasma creatinine was used to estimate GFR by the
      simplified Modification of Diet in Renal Disease (MDRD) equation. In men with a
      GFR <60 ml/min/1.73 m(2), triglycerides, non-high-density lipoprotein (HDL),
      apoprotein B, fibrinogen, soluble tumor necrosis factor receptor (sTNFR-2) and
      vascular cell adhesion molecule-1 (VCAM) were significantly higher when compared
      to the referent group (GFR> or =90 ml/min/1.73 m(2)). In multivariable logistic
      regression, those in the highest quartiles of the following biomarkers had
      increased odds of having a GFR <60 ml/min/1.73 m(2) when compared to those in the
      lowest quartiles: triglycerides (odds ratio (OR) 3.11; 95% CI, 1.52-6.36),
      fibrinogen (OR 5.40; 95% CI 2.14-13.65), sTNFR-2 (OR 8.34; 95% CI 3.50-19.88) and
      VCAM (OR 4.50; 95% CI 1.98-10.23). An inverse association was observed for HDL
      (OR 0.48; 95% CI 0.24-0.98). We found no association between C-reactive protein
      and GFR. The results were similar when creatinine clearance by Cockcroft-Gault
      was used to estimate kidney function. We conclude that several potentially
      modifiable lipid and inflammatory biomarkers are elevated in the setting of
      moderately decreased GFR in men with type II DM and may be the link between renal
      insufficiency and increased risk for cardiovascular events in this population.

PMID- 16408126
TI  - Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with an increased risk of
      cardiovascular morbidity and mortality. Arterial stiffness and remodeling have
      been well documented in patients with end-stage renal disease, but little is
      known about arterial phenotype in CKD patients with moderate reduction in
      glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/
      s.d.) with CKD and GFR measured by renal clearance of (51)Cr
      ethylenediaminetetraacetate were compared to 121 hypertensive patients without
      CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid
      artery diameter, intima-media thickness (IMT), distensibility, and Young's
      elastic modulus were noninvasively determined with a high-definition echotracking
      system. Patients with CKD had a significantly larger carotid internal diameter
      than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/
      0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in
      circumferential wall stress, respectively, since no significant difference in IMT
      was observed. Carotid distensibility and elastic modulus did not significantly
      differ between CKD and hypertensives; normotensives had significantly higher
      distensibility and lower elastic modulus than CKD and hypertensive patients.
      Carotid-femoral pulse wave velocity was significantly higher in CKD patients than
      in hypertensives and normotensives. In multivariate analyses either involving the
      entire population or restricted to CKD patients, GFR was independently and
      strongly related to carotid diameter and elastic modulus. Arterial enlargement
      and increased arterial stiffness occur in parallel with the decline in renal
      function in patients with mild-to-moderate CKD.

PMID- 16408127
TI  - Differential regulation of metzincins in experimental chronic renal allograft
      rejection: potential markers and novel therapeutic targets.
AB  - Chronic renal allograft rejection is characterized by alterations in the
      extracellular matrix compartment and in the proliferation of various cell types.
      These features are controlled, in part by the metzincin superfamily of metallo
      endopeptidases, including matrix metalloproteinases (MMPs), a disintegrin and
      metalloproteinase (ADAM) and meprin. Therefore, we investigated the regulation of
      metzincins in the established Fisher to Lewis rat kidney transplant model.
      Studies were performed using frozen homogenates and paraffin sections of rat
      kidneys at day 0 (healthy controls) and during periods of chronic rejection at
      day +60 and day +100 following transplantation. The messenger RNA (mRNA)
      expression was examined by Affymetrix Rat Expression Array 230A GeneChip and by
      real-time Taqman polymerase chain reaction analyses. Protein expression was
      studied by zymography, Western blot analyses, and immunohistology. mRNA levels of
      MMPs (MMP-2/-11/-12/-14), of their inhibitors (tissue inhibitors of
      metalloproteinase (TIMP)-1/-2), ADAM-17 and transforming growth factor (TGF)
      beta1 significantly increased during chronic renal allograft rejection. MMP-2
      activity and immunohistological staining were augmented accordingly. The most
      important mRNA elevation was observed in the case of MMP-12. As expected, Western
      blot analyses also demonstrated increased production of MMP-12, MMP-14, and TIMP
      2 (in the latter two cases as individual proteins and as complexes). In contrast,
      mRNA levels of MMP-9/-24 and meprin alpha/beta had decreased. Accordingly, MMP-9
      protein levels and meprin alpha/beta synthesis and activity were downregulated
      significantly. Members of metzincin families (MMP, ADAM, and meprin) and of TIMPs
      are differentially regulated in chronic renal allograft rejection. Thus, an
      altered pattern of metzincins may represent novel diagnostic markers and possibly
      may provide novel targets for future therapeutic interventions.

PMID- 16408128
TI  - Metabolic syndrome and chronic kidney disease in Okinawa, Japan.
AB  - We assessed the prevalence of chronic kidney disease (CKD) in a hospital-based
      screening program in Okinawa, Japan. The significance of metabolic syndrome as a
      determinant of CKD was examined using multivariate logistic regression analysis.
      A total of 6980 participants, aged 30-79 years, participated in a screening
      program in Tomishiro Chuo Hospital. Metabolic syndrome was defined according to
      the criteria of the Adult Treatment Panel III (ATP III). Data were also analyzed
      according to the modified criteria of the National Cholesterol Education Program
      (NCEP) that defines abdominal obesity as a waist circumference of > oe =85 cm in
      men and > or =90 cm in women. CKD was defined as dipstick proteinuria (> or =1+)
      or a reduced glomerular filtration rate (GFR). GFR was estimated using the
      abbreviated Modification of Diet in Renal Disease (MDRD) formula. The prevalence
      of metabolic syndrome and CKD was 12.8 and 13.7%, respectively. Metabolic
      syndrome was a significant determinant of CKD (adjusted odds ratio (OR) 1.537 and
      95% confidence interval (CI) 1.277-1.850, P<0.0001). The adjusted OR (95% CI) was
      1.770 (1.215-2.579, P=0.0029) for those with four metabolic syndrome risk factors
      compared to those with no metabolic syndrome risk factors. Metabolic syndrome was
      a significant determinant for younger participants (<60 years; OR 1.686, 95% CI
      1.348-2.107, P<0.0001), but not for older participants (> or =60 years; OR 1.254,
      95% CI 0.906-1.735, NS). The relationship between the number of metabolic
      syndrome risk factors and the prevalence of CKD was linear using the modified
      criteria. The results suggest that metabolic syndrome is a significant
      determinant of CKD in men under 60 years of age, in Okinawa, Japan.

PMID- 16408129
TI  - The progression of chronic kidney disease: a 10-year population-based study of
      the effects of gender and age.
AB  - The increase in demand for renal replacement therapy makes it important to
      investigate the prognosis of the earlier stages of chronic kidney disease (CKD).
      We examined the change in glomerular filtration rate (GFR), and patient and renal
      survival in CKD stage 3 in the municipality of Tromso, a well-defined European
      community with a population of 58,000. All patients with estimated GFR between 30
      and 59 ml/min/1.73 m(2) for more than 3 months during a 10-year study period were
      identified from a complete database of all 248 560 measurements of serum
      creatinine made in the community in the study period. Change in GFR was estimated
      for each patient using a multilevel model. A complete follow-up with respect to
      patient and renal survival was obtained from hospital databases. A total of 3047
      patients was included. The median number of measurements of creatinine for each
      patient was 9, and the median observation time was 44 months. Mean estimated
      change in GFR was--1.03 ml/min/1.73 m(2)/year. Seventy-three percent of the
      patients experienced a decline in GFR. The 10-year cumulative incidence of renal
      failure was 0.04 (95% CI 0.03-0.06) and mortality 0.51 (95% CI 0.48-0.55). Female
      gender was associated with slower decline in GFR and better patient and renal
      survival. In this population-based study, the decline in GFR in CKD was slower
      than in previously studied selected patient groups. A high mortality pre-empted
      the development of renal failure in many patients. The prognosis of CKD depended
      strongly on gender.

PMID- 16408130
TI  - Assessment of glomerular filtration rate in addition to albuminuria is important
      in managing type II diabetes.
AB  - Although much emphasis has been placed on screening for albuminuria in type II
      diabetic patients, less attention has been focused on the role of glomerular
      filtration rate (GFR) in the assessment of risk. Herein, we examined the
      association between GFR and vascular complications in a consecutive cohort of
      5174 type II diabetic patients between 1995 and 2000. Renal function was assessed
      by GFR (estimated by Modification of Diet in Renal Disease equation). The
      frequency of chronic kidney disease (CKD) as defined by GFR <60 ml/min/1.73 m(2),
      micro- and macrovascular complications, and their associations were analyzed. In
      this study cohort, 6% had serum creatinine > or =150 micromol/l and 15.8% had
      CKD. After adjustment for potential confounders, including urinary albumin
      excretion, odds ratios [95% confidence interval (CI)] across different stages of
      estimated GFR (> or =90, 60-89, 30-59, 15-29, <15 ml/min/1.73 m(2)) for
      macrovascular disease were 1.00, 1.42 [1.12-1.80], 1.80 [1.32-2.45], 2.74 [1.64
      4.56], and 4.05 [1.77-9.26], respectively (P for trend <0.001); for retinopathy
      were 1.00, 1.23 [1.04-1.46], 1.80 [1.40-2.30], 2.05 [1.25-3.37], and 4.12 [1.56
      10.90], respectively (P for trend <0.001); for sensory neuropathy were 1.00,
      1.53[1.27-1.85], 2.09 [1.58-2.76], 4.32 [2.41-7.77], and 3.16 [1.25-8.02],
      respectively (P for trend <0.001); and for microalbumuria (with GFR <15
      ml/min/1.73 m(2) excluded from the analysis) were 1.00, 1.51 [1.30-1.75], 5.80
      [4.52-7.44], and 52.5 [16.4-168.2] respectively (P for trend <0.001). Measurement
      of serum creatinine alone without GFR may underestimate renal impairment in type
      II diabetic patients. Decreasing GFR was significantly associated with increasing
      frequency of micro- and macrovascular complications.

PMID- 16408131
TI  - N2-carboxyethyl-2'-deoxyguanosine, a DNA glycation marker, in kidneys and aortas
      of diabetic and uremic patients.
AB  - Advanced glycation end product (AGE)-mediated modification of proteins is
      enhanced both in the kidneys and aortas of diabetic and uremic patients. However,
      AGE modification of deoxyribonucleic acid (DNA) has not yet been reported in
      these patients. We performed immunohistochemistry of kidneys and aortas using a
      monoclonal antibody against N(2)-carboxyethyl-2'-deoxyguanosine (CEdG), a marker
      of AGE-linked DNA. A total of 20 kidneys and 20 aortas were obtained by autopsy.
      The kidney samples consisted of two groups: nondiabetic nonkidney disease
      (control) and diabetic nephropathy. The aorta samples consisted of four groups:
      nondiabetic nonkidney disease (control), diabetes, hemodialysis, and diabetic
      hemodialysis. In the kidneys CEdG was detected predominantly in the nuclei of
      epithelial cells, mesangial cells, and endothelial cells of the glomeruli,
      parietal epithelial cells, and tubular cells. The number of CEdG-positive cells
      in the glomeruli was significantly increased in diabetic nephropathy compared
      with control. In the aortic walls, CEdG was detected predominantly in the nuclei
      of macrophages and myofibroblasts. The number of CEdG-positive cells in the aorta
      was significantly increased in hemodialysis patients and diabetic hemodialysis
      patients compared with control. The highest number of CEdG-positive cells in the
      aorta was observed in diabetic hemodialysis patients. In conclusion, AGE-mediated
      modification of DNA is enhanced in the kidney of diabetic nephropathy and the
      aorta of uremic atherosclerosis, and may induce a loss of genetic integrity in
      these diseases.

PMID- 16408132
TI  - Dedicated outpatient vascular access center decreases hospitalization and missed
      outpatient dialysis treatments.
AB  - Dedicated outpatient vascular access centers (VAC) specializing in percutaneous
      interventions (angiography, thrombectomy, angioplasty and catheter placement)
      provide outpatient therapy that can obviate the need for hospitalization. This
      paper reports the impact of one VAC staffed by interventional nephrologists on
      vascular access-related hospitalization and missed outpatient dialysis
      treatments. We performed a retrospective analysis of vascular access-related
      hospitalized days and missed vascular access-related outpatient dialysis
      treatments from 1995 to 2002 in 21 Phoenix Arizona Facilities (5928 cumulative
      patients) and 1275 cumulative Fresenius Medical Care North America (FMCNA)
      facilities (289,454 cumulative patients) to evaluate the impact of the
      introduction of a VAC in Phoenix. Vascular access-related hospitalized
      days/patient year and missed dialysis treatments/patient year declined from 1997
      to 2002 across all access types. The decline was greater in Phoenix and coincided
      with the creation of a VAC in 1998. By 2002, there were 0.57 fewer hospitalized
      days/patient year and 0.29 fewer missed treatments/patient year than in the
      national sample (P<0.01). In 2002, the relative risk for vascular access
      hospitalized days was 0.38 (95% confidence interval (CI) 0.27-0.5) (P<0.01) and
      for vascular access-related missed outpatient dialysis treatments was 0.34 (95%
      CI 0.24-0.49) (P<0.01) in Phoenix vs FMCNA after adjustment for age, gender,
      diabetic status duration of dialysis and access type. VAC development was
      associated with a significant decrease in vascular access-related hospitalization
      and missed outpatient dialysis treatments. Further studies are necessary to
      demonstrate this effect in other communities.

PMID- 16408133
TI  - Glomerular filtration rate estimated by cystatin C among different clinical
      presentations.
AB  - Glomerular filtration rate (GFR) estimates from serum creatinine has not been
      generalizable across all populations. Cystatin C has been proposed as an
      alternative marker for estimating GFR. The objective of this study was to compare
      cystatin C with serum creatinine for estimating GFR among different clinical
      presentations. Cystatin C and serum creatinine levels were obtained from adult
      patients (n=460) during an evaluation that included a GFR measurement by
      iothalamate clearance. Medical records were abstracted for clinical presentation
      (healthy, native chronic kidney disease or transplant recipient) at the time of
      GFR measurement. GFR was modeled using the following variables: cystatin C (or
      serum creatinine), age, gender and clinical presentation. The relationship
      between cystatin C and GFR differed across clinical presentations. At the same
      cystatin C level, GFR was 19% higher in transplant recipients than in patients
      with native kidney disease (P<0.001). The association between cystatin C and GFR
      was stronger among native kidney disease patients than in healthy persons
      (P<0.001 for statistical interaction). Thus, a cystatin C equation was derived
      using only patients with native kidney disease (n=204). The correlation with GFR
      (r(2)=0.853) was slightly higher than a serum creatinine equation using the same
      sample (r(2)=0.827), the Modification of Diet in Renal Disease equation
      (r(2)=0.825) or the Cockcroft-Gault equation (r(2)=0.796). Averaged estimates
      between cystatin C and serum creatinine equations further improved correlation
      (r(2)=0.891). Cystatin C should not be interpreted as purely a marker of GFR.
      Other factors, possibly inflammation or immunosuppression therapy, affect
      cystatin C levels. While recognizing this limitation, cystatin C may improve GFR
      estimates in chronic kidney disease patients.

PMID- 16408134
TI  - Prognostic importance of clinic and home blood pressure recordings in patients
      with chronic kidney disease.
AB  - Blood pressure (BP) measured only in the clinic substantially misclassifies
      hypertension in patients with chronic kidney disease (CKD). The role of out-of
      clinic recordings of BP in predicting end-stage renal disease (ESRD) and death in
      patients with CKD is unknown. A prospective cohort study was conducted in 217
      Veterans with CKD. BP was measured at home and in the clinic by 'routine' and
      standardized methods. Patients were followed over a median of 3.5 years to assess
      the end points of total mortality, ESRD or the composite outcome of ESRD or
      death. Home BP was 147.0+/-21.4/78.3+/-11.6 mmHg and clinic BPs were 155.2+/
      25.6/84.7+/-14.2 mmHg by standardized method and 144.5+/-24.2/75.4+/-14.7 mmHg by
      the 'routine' method. The composite renal end point occurred in 75 patients
      (34.5%), death in 52 patients (24.0%), and ESRD in 36/178 patients (20.2%). One
      standard deviation (s.d.) increase in systolic BP increased the risk of renal end
      point by 1.27 (95% confidence interval (CI) 1.01-1.60) for routine clinic
      measurement, by 1.69 (95% CI 1.32-2.17) for standardized clinic measurement and
      by 1.84 (95% CI 1.46-2.32) for home BP recording. One s.d. increase in home
      systolic BP increased the risk of ESRD by 1.74 (95% CI 1.04-2.93) when adjusted
      for standardized clinic systolic BP, proteinuria, estimated glomerular filtration
      rate, and other risk factors. In patients with CKD, BPs obtained at home are a
      stronger predictor of ESRD or death compared to BPs obtained in the clinic.
      Systolic home BP is an independent predictor for ESRD.

PMID- 16408135
TI  - Paraplegia, proteinuria, and renal failure.

PMID- 16408136
TI  - Quantitative analysis of the dysnatremias.

PMID- 16408139
TI  - Treatments for unwanted facial hair.
AB  - Twenty-two percent of women in North America have unwanted facial hair, which can
      cause embarrassment and result in a significant emotional burden. Treatment
      options include plucking, waxing (including the sugar forms), depilatories,
      bleaching, shaving, electrolysis, laser, intense pulsed light (IPL), and
      eflornithine 13.9% cream (Vaniqa, Barrier Therapeutics in Canada and Shire
      Pharmaceuticals elsewhere). Eflornithine 13.9% cream is a topical treatment that
      does not remove the hairs, but acts to reduce the rate of growth and appears to
      be effective for unwanted facial hair on the mustache and chin area. Eflornithine
      13.9% cream can be used in combination with other treatments such as lasers and
      IPL to give the patient the best chance for successful hair removal.

PMID- 16408140
TI  - Famciclovir for the treatment of recurrent genital and labial herpes lesions.
AB  - Famciclovir (Famvir, Novartis) is an effective treatment for herpes zoster and
      herpes simplex. Two separate studies recently examined the effectiveness of
      single high doses of famciclovir for treating recurrent genital herpes and labial
      herpes (cold sores). In the randomized, placebo-controlled studies, patients
      initiated treatment at the first onset of symptoms. For the treatment of genital
      herpes, a 1,000 mg b.i.d. dose of famciclovir had significant advantages over the
      placebo, reducing the time required to heal the lesions, preventing the
      development of lesions beyond the papule stage, and improving the time to
      resolution of all symptoms. For the treatment of labial herpes, a single 1,500 mg
      dose of famciclovir shortened the lesion healing time, shortened the time to
      normal skin, and resulted in faster resolution of pain and tenderness.

PMID- 16408141
TI  - Her-2/neu expression in primary breast cancer with sentinel lymph node
      metastasis.
AB  - BACKGROUND: Amplification of the protein product of the HER-2/neu oncogene in
      primary breast cancer specimens is associated with an adverse prognosis. We
      hypothesized that overexpression of HER-2/neu would predict metastases to the
      sentinel lymph nodes (SLNs). METHODS: A retrospective review of a prospective
      nonrandomized evaluation of 1055 clinically node-negative breast cancer patients
      undergoing 1063 SLN biopsies was performed. HER-2/neu analysis was performed by
      immunohistochemistry and, in selected cases, by fluorescence in situ
      hybridization. Clinical, demographic, surgical, radiological, and pathologic data
      were analyzed by using generalized estimating equations logistic regression
      models. RESULTS: Two hundred thirty-two (23.6%) of 985 operations in which the
      SLN was found at operation resulted in positive nodes. In a multivariate
      analysis, size (P < .0001) and HER-2/neu overexpression (P = .026) were
      independent predictors of SLN metastasis. CONCLUSIONS: Size is a known predictor
      of SLN metastasis in the modern SLN era, as it was in the pre-SLN eras. HER-2/neu
      was found to be significantly predictive of SLN metastasis in our study. We
      anticipate a future when even the relatively minor procedure of SLN biopsy might
      be avoided with the predictive information gained from studying the pathology and
      molecular markers of primary breast cancers.

PMID- 16408142
TI  - Surgery should be the primary treatment of synchronous colorectal metastases in
      the asymptomatic patient [corrected].

PMID- 16408143
TI  - Light harvesting unsymmetrical conjugated dendrimers as photosynthetic mimics.
AB  - We review the synthesis and photophysical properties of light harvesting
      phenylacetylene dendrimers with unsymmetrical branching. We describe the steady
      state and time dependent experiments that are used to characterize energy
      transfer properties in the conjugated dendrimers. Finally, we describe
      investigations of the unsymmetrical phenylacetylene dendrimers as potential
      materials for applications in fluorescence-based sensors, and for non-linear
      optics.

PMID- 16408145
TI  - Organic solar cells: an overview focusing on active layer morphology.
AB  - Solar cells constructed of organic materials are becoming increasingly efficient
      due to the discovery of the bulk heterojunction concept. This review provides an
      overview of organic solar cells. Topics covered include: a brief history of
      organic solar cell development; device construction, definitions, and
      characteristics; and heterojunction morphology and its relation to device
      efficiency in conjugated polymer/fullerene systems. The aim of this article is to
      show that researchers are developing a better understanding of how material
      structure relates to function and that they are applying this knowledge to build
      more efficient light-harvesting devices.

PMID- 16408144
TI  - Light harvesting dendrimers.
AB  - Tree-like dendrimers with decreasing number of chromophores from periphery to
      core is an attractive candidate for light-harvesting applications. Numerous
      dendritic designs with different kinds of light-collecting chromophores at
      periphery and an energy-sink at the core have been demonstrated with high energy
      transfer efficiency. These building blocks are now being developed for several
      applications such as light-emitting diodes, frequency converters and other
      photonic devices. This review outlines the efforts that are based on both
      conjugated and non-conjugated dendrimers.

PMID- 16408146
TI  - Self-organization of porphyrins and fullerenes for molecular photoelectrochemical
      devices.
AB  - We have constructed a variety of molecular assemblies of porphyrin as a donor and
      fullerene as an acceptor on electrodes for molecular photoelectrochemical
      devices. Highly efficient energy- and electron-transfer processes have been
      realized at gold electrodes modified with self-assembled monolayers of porphyrin-
      or fullerene linked systems mimicking light-harvesting and charge separation in
      bacterial photosynthesis. Highly ordered organization of porphyrins and
      fullerenes has also been achieved using step-by-step self-assembly of porphyrin
      and fullerene units by association with gold nanoparticles or dendrimers on tin
      oxide electrodes, which exhibit high power-conversion efficiency of up to 1.5%.
      These results will provide valuable information on the design of donor-acceptor
      type molecular assemblies that can be tailored to construct highly efficient
      organic solar cells.

PMID- 16408147
TI  - Stabilisation of emissive charge-separated states in pi-stacked donor-acceptor
      ensembles.
AB  - pi-Stacking of an electron donor and acceptor minimises reorganisation energy and
      stabilises charge-separated state.

PMID- 16408149
TI  - Usefulness of urine dipstick in an urogynecologic population.
AB  - Urine dipstick alone is insufficient for diagnosing urinary tract infection in
      patients with pelvic floor disorders.

PMID- 16408148
TI  - Time trends of age-adjusted incidence rates of first hip fractures: a register
      based study among older people in Viborg County, Denmark, 1987-1997.
AB  - INTRODUCTION: A retrospective cohort study was performed to investigate if
      incidence rates of first hip fractures are changing in a Danish county. Study
      material was obtained from an excerpt from a computerized national health
      register and covers the period 1987-1997. METHODS: First hip fractures were
      identified through a search 10 years back from the date of admission. To assess
      the 20-year trend, 1978 data were included. The study period saw inclusion of
      3,036 first (1987-1997) and 122 first and recurrent (1978) hip fracture patients
      aged 50 years and older. Data were analyzed using weighted regression analysis.
      RESULTS: Age-adjusted first hip fracture incidence rates increased significantly
      (P<0.001) for women, men, and pertrochanteric fractures. The rate of increase was
      18 [95% confidence interval (CI), 12-25], 8 (95% CI, 4-12), and 10 (95% CI, 7-12)
      per 100,000 per year for women, men, and pertrochanteric fractures, respectively.
      The age-adjusted rate for both genders combined was 425 per 100,000 in 1997 (95%
      CI, 380-470). The incidence of cervical fractures was stable. If the rates of
      1978 were included in the analysis, the cervical hip fractures also increased
      (P<0.001). The weighted average of female-male ratio was a stable 2.6 (95% CI,
      2.4-2.8). Cervical-pertrochanteric ratio dropped to 1.2:1 (P<0.001). Mean age at
      admission rose from 78.9 to 80.8 years. CONCLUSION: In conclusion, the results
      provided support for an increasing incidence of first hip fractures, even when
      aging of the population was accounted for.

PMID- 16408150
TI  - Urinary retention following tension-free vaginal tape successfully treated by
      sacral neuromodulation.
AB  - Postoperative urinary retention following anti-incontinence surgery has
      traditionally been thought to be due to overcorrection. There is increasing
      evidence, however, that a neurogenic component may also play a significant role.
      This is a case report of a 72-year-old woman who developed delayed partial
      urinary retention following a tension-free vaginal tape which resolved with
      initial sacral neuromodulation.

PMID- 16408151
TI  - Predictors of the working alliance in assertive community treatment.
AB  - Past research has found that a positive working alliance between clients and
      their case managers is modestly correlated with client outcomes. The current
      study tried to identify the predictors of the working alliance in a sample of 115
      clients who were receiving services from Assertive Community Treatment (ACT)
      teams. All of the clients suffered from severe mental illness, had a substance
      use disorder and were homeless at baseline. Both the client's rating and the case
      manager's rating of the working alliance were assessed at 3 months and 15 months
      post baseline. Client characteristics, particularly motivation to change,
      explained more of the variance of the client's rating of the alliance than
      treatment variables or client change on the outcome variables. On the other hand,
      treatment variables (e.g., the amount of transportation services provided) and
      client change on the outcome variables explained more of the variance of the case
      manager's rating of the alliance.

PMID- 16408152
TI  - Determinants of health plan membership among patients in routine U.S. psychiatric
      practice.
AB  - This study utilized a large clinical dataset of patients representative of those
      in routine U.S. psychiatric practice to assess the influence of sociodemographic
      variables and diagnostic class on health plan membership (public or private).
      Data on patients with schizophrenia or other psychotic disorders (n=288) and
      patients with mood or anxiety disorders (n=1304) were obtained from a cross
      sectional practice-based survey conducted by the American Psychiatric Institute
      for Research and Education. The likelihood of health plan membership was lower
      among males and among those from a minority race/ethnicity. Health plan
      membership was also affected by educational attainment and employment status.
      Even after controlling for these sociodemographic determinants of health plan
      membership, individuals with schizophrenia/other psychotic disorders were
      significantly less likely to belong to a health plan than those with mood/anxiety
      disorders.

PMID- 16408153
TI  - Headache in patients with chronic obstructive pulmonary disease: effects of
      chronic hypoxaemia.
AB  - The frequency and characteristics of headache in patients with chronic
      obstructive pulmonary disease (COPD) are not clear and there are only a few
      studies that have assessed the relationship between chronic hypoxaemia and
      headache. We performed this study in order to evaluate the frequency and
      characteristics of headache in COPD patients. A total of 119 patients, with a
      mean age of 63.4 +/- 8.2 years, diagnosed with moderate or severe stable COPD
      were included in the study. Overall 31.9% of the patients complained of headache
      and 45.4% were reported to have sleep disorders. There were significant effects
      of family history of COPD, having other systemic disorders or sleep disorders
      (snoring, bruxism, restless leg syndrome, etc.) and laboratory data of chronic
      hypoxaemia and airway obstruction on headache co-morbidity. In conclusion,
      possibly being a specific subtype of elderly headache, headache in patients with
      moderate or severe COPD is a common problem and future studies are needed to
      obtain more knowledge about its pathophysiological and clinical basis.

PMID- 16408154
TI  - Thyroid dysfunction and headache.
AB  - An observational study of thyroid function tests performed in patients with
      headache prior to referral to a neurological clinic found no headache cases
      attributable to either hypothyroidism or hyperthyroidism. The role of thyroid
      dysfunction in the aetiology of headache remains uncertain.

PMID- 16408159
TI  - Prokaryotic expression of antibodies.
AB  - Maximizing the expression yields of recombinant whole antibodies and antibody
      fragments such as Fabs, single-chain Fvs and single-domain antibodies is highly
      desirable since it leads to lower production costs. Various eukaryotic and
      prokaryotic expression systems have been exploited to accommodate antibody
      expression but Escherichia coli systems have enjoyed popularity, in particular
      with respect to antibody fragments, because of their low cost and convenience. In
      many instances, product yields have been less than adequate and intrinsic and
      extrinsic variables have been investigated in an effort to improve yields. This
      review deals with various aspects of antibody expression in E. coli with a
      particular focus on single-domain antibodies.

PMID- 16408158
TI  - Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of
      therapeutic anti-cancer monoclonal antibodies.
AB  - In recent years, interest in anti-cancer therapeutic monoclonal antibodies (mAb)
      has been renewed. Several of these reagents have been approved for therapy in a
      variety of cancer patients and many others are in different stages of
      development. It is believed that multiple mechanisms are involved in the anti
      cancer effects of these reagents. However, several in vitro and in vivo studies
      have demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) is
      their predominant mode of action against cancer cells. The requirement for a
      direct interaction between mAb and receptors for the Fc region of the antibodies
      (FcR) has been demonstrated for anti-tumor effects of these antibodies.
      Consequently, FcR-bearing immune effector cells play an important role in
      mediating their effects. It is not surprising that cancer cells have developed
      different strategies to evade these antibodies. Several strategies are proposed
      to potentiate the mAb-mediated ADCC in cancer patients. They may enhance anti
      cancer therapeutic effects of these regents.

PMID- 16408160
TI  - Antibody-based therapeutics: focus on prostate cancer.
AB  - The recent clinical and commercial success of anti-cancer antibodies such as
      rituximab, trastuzumab, cetuximab and bevacizumab has continued to foster great
      interest in antibody-based therapeutics for the treatment of both hematopoietic
      malignancies and solid tumors. Given the likely lower toxicity for antibodies
      which, in contrast with traditional cytotoxic small molecule drugs, target tumor
      cells and have a lower impact on non-malignant by-stander organs, the potential
      increases in efficacy associated with conjugation to radioisotopes and other
      cellular toxins and the ability to characterize the target with clinical
      laboratory diagnostics to improve the drugs clinical performance, it is
      anticipated that current and future antibody therapeutics will find substantial
      roles alone and in combination therapy strategies for the treatment of patients
      with cancer. A significant number of cell surface proteins, glycoproteins,
      receptors, enzymes and peptides have been discovered that have become targets for
      the treatment of advanced hormone-refractory prostate cancer. A variety of naked
      antibodies and antibody conjugates have currently progressed through preclinical
      development and are in early or more advanced stages of clinical development.
      Clinicians, scientists and prostate cancer patients are all keenly interested to
      learn whether these agents when administered alone or in combination with other
      hormonal-based and cytotoxic therapies will show lasting benefit for sufferers of
      this common disease.

PMID- 16408161
TI  - Antibody-guided radiation therapy of cancer.
AB  - Radioimmunotherapy (RIT) using radiolabeled monoclonal antibodies (MAbs) directed
      against tumor-associated antigens has evolved from an appealing concept to one of
      the standard treatment options for patients with non-Hodgkin's lymphoma (NHL).
      Inefficient localization of radiolabeled MAbs to nonhematological cancers due to
      various tumor-related factors, however, has refrained RIT from outgrowing the
      experimental stage in solid tumors. Still, small volume or minimal residual
      disease has been recognized as a potentially suitable target for radiolabeled
      antibodies. Several strategies are being explored aimed at improving the
      targeting of radiolabeled MAbs to solid tumors thus improving their therapeutic
      efficacy. In this review, a historical overview of the application of RIT is
      given and various aspects of the application of radiolabeled MAbs as anti-cancer
      agents are discussed. Finally, the clinical results of RIT of NHL, colorectal
      cancer, ovarian cancer, breast cancer, and renal cell cancer are reviewed.

PMID- 16408162
TI  - Development and regulation of monoclonal antibody products: challenges and
      opportunities.
AB  - An increasing number of monoclonal antibodies for cancer diagnosis and treatment
      are in clinical use and in the development pipeline, with more expected as new
      molecular targets are identified. As with all drugs, product quality, an
      appropriate pre-clinical pharmacology-toxicology testing program, and well
      designed clinical trials are essential for a successful drug development program.
      However, protein products such as monoclonal antibodies present unique regulatory
      concerns. The derivation from biological sources as well as the constantly
      evolving technologies utilized to develop these products demands continuous
      appraisal of safety concerns, even while the accumulated experience with these
      protein products has facilitated their safety evaluations. Because of the complex
      nature of these products and their inherent heterogeneity, a mechanistic
      understanding of the mode of action along with careful attention to product
      design and manufacture are critical to assuring a safe, effective and consistent
      product. Protein products may be highly species specific, thus pharmacologically
      relevant animal models are an important component in accurately assessing pre
      clinical safety and establishing initial dosing. Furthermore, the immunogenicity
      of protein products can impact its safety profile, dose exposure, and efficacy.
      Mechanistic insight should form the basis of biological assays used for
      monitoring efficacy, safety, lot-to-lot consistency and manufacturing changes.
      The inherent uniqueness of each product necessitates a flexible case-by-case
      approach for biologics review that is based on a strong scientific understanding
      of relative risks. This review will provide an overview of approaches used in the
      development of antibody-based cancer therapeutics and the scientific basis of
      regulatory reviews.

PMID- 16408163
TI  - Designing antibodies for oncology.
AB  - The past five years have witnessed the emergence of monoclonal antibodies as
      important therapeutics for cancer treatment. Lower toxicity for antibodies versus
      small molecules, the potential for increased efficacy by conjugation to
      radioisotopes and cellular toxins, or the ability to exploit immune cell
      functions have led to clinical performances on par or superior to conventional
      drug therapies. This review outlines the various immunoglobulin design strategies
      currently available, techniques used to reduce Ig antigenicity and toxicity, and
      points to consider during the manufacture of antibodies for use in clinical
      oncology.

PMID- 16408165
TI  - [Drug-induced pulmonary damage].
AB  - The frequency of drug-induced damage to the lung in inpatients is estimated to be
      about 10%. Pathoanatomically, varying damage patterns result, ranging from acute
      pulmonary edema via inflammatory reactions to pulmonary fibrosis. The ATS/ERS
      2001 classification, which is based on the suggestions made by Liebow 1969, is an
      accepted system for classifying findings according to recurring patterns.
      Generally, there are no specific morphological findings which allow safe
      conclusions on possible administered drugs. Clinical information is mandatory.
      Differentiation from pulmonary alterations due to the underlying disease is often
      difficult. In daily routine diagnostics, it is important to consider iatrogenic
      causal factors in cases of "undetermined pulmonary disease".

PMID- 16408166
TI  - Effects of noise-induced hearing loss at young age on voice onset time and gap-in
      noise representations in adult cat primary auditory cortex.
AB  - Here we show that mild hearing loss induced by noise exposure in early age causes
      a decrease in neural temporal resolution when measured in adulthood. We
      investigated the effect of this chronic hearing loss on the representation of a
      voice onset time (VOT) and a gap-duration continuum in primary auditory cortex
      (AI) in cats, which were exposed at the age of 6 weeks to a 120-dB SPL, 5-kHz 1/3
      octave noise band for 2 h. The resulting hearing loss measured using auditory
      brainstem responses and cortical multiunit thresholds at 4-6 months of age was 20
      40 dB between 1 and 32 kHz. Multiple single-unit activity was recorded in seven
      noise-exposed cats and nine control cats related to the presentation of a/ba/
      /pa/ continuum in which VOT was varied in 5-ms step from 0 to 70 ms. We also
      obtained data for noise bursts with gaps, of duration equal to the VOT, embedded
      in noise 5 ms after the onset. Both stimuli were presented at 65 dB SPL. Minimum
      VOT and early-gap duration were defined as the lowest value in which an on
      response, significantly above the spontaneous activity, to both the leading and
      trailing noise bursts or vowel was obtained. The mild chronic noise-induced
      hearing loss increased the minimum detectable VOT and gap duration by 10 ms. We
      also analyzed the maximum firing rate (FRmax) and the latency of the responses as
      a function of VOT and gap duration and found a significant reduction in the FRmax
      to the trailing noise burst for gap durations above 50 ms. This suggests that
      mild hearing loss acquired in early age may affect cortical temporal processing
      in adulthood.

PMID- 16408167
TI  - Progression of inner ear pathology in Ames waltzer mice and the role of
      protocadherin 15 in hair cell development.
AB  - The Ames waltzer (av) mouse mutant exhibits auditory and vestibular abnormalities
      resulting from mutation of protocadherin 15 (Pcdh15). Ames waltzer has been
      identified as an animal model for inner ear pathology associated with Usher
      syndrome type 1F. Studies correlating anatomical phenotype with severity of
      genetic defect in various av alleles are providing better understanding of the
      role played by Pcdh15 in inner ear development and of sensorineural abnormalities
      associated with alterations in Pcdh15 protein structure as a result of gene
      mutation. In this work we present new findings on inner ear pathology in four
      alleles of av mice with differing mutations of Pcdh15 as well as varying
      alterations in inner ear morphology. Two alleles with in-frame deletion mutations
      (Pcdh15 (av-J) and Pcdh15 (av-2J)) and two presumptive functional null alleles
      (Pcdh15 (av-3J) and Pcdh15 (av-Tg)) were studied. Light and electron microscopic
      observations demonstrated that the severity of cochlear and vestibular pathology
      in these animals correlates positively with the extent of mutation in Pcdh15 from
      embryonic day 18 (E18) up to 12 months. Electron microscopic analysis of immature
      ears indicated early abnormalities in the arrangement of stereocilia and the
      inner and outer hair cell cuticular plates, stereocilia rootlets, and the actin
      meshwork within the cuticular plate. In severe cases, displacement of the
      kinocilium and alterations in the shape of the cuticular plate was also observed.
      Mice harboring in-frame deletion mutations showed less disorganization of
      stereocilia and cuticular plates in the organ of Corti than the presumptive
      functional null alleles at P0-P10. A slower progression of pathology was also
      seen via light microscopy in older animals with in-frame deletions, compared to
      the presumptive functional null mutations. In summary, our results demonstrate
      that mutation in Pcdh15 affects the initial formation of stereocilia bundles with
      associated changes in the actin meshwork within the cuticular plate; these
      effects are more pronounced in the presumed null mutation compared to mutations
      that only affect the extracellular domain. The positive correlation of severity
      of effects with extent of mutation can be seen well into adulthood.

PMID- 16408168
TI  - An interstitial network of podoplanin-expressing cells in the human endolymphatic
      duct.
AB  - The human endolymphatic duct (ED) with encompassing interstitial connective
      tissue (CT) is believed to be important for endolymph resorption and fluid
      pressure regulation of the inner ear. The periductal CT cells are interconnected
      via numerous cellular extensions, but do not form vessel structures. Here we
      report that the periductal CT is populated by two distinct cell phenotypes; one
      expressing podoplanin, a protein otherwise found on lymph endothelia and on
      epithelia involved in fluid fluxes, and a second expressing a fibroblast marker.
      A majority of the interstitial cells expressed podoplanin but not the lymphatic
      endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial
      growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were
      found close to the ED epithelium. In the mid- and distal parts of the ED, these
      cells were enriched under folded epithelia. Furthermore, subepithelial CT cells
      were found to express activated platelet derived growth factor (PDGF)-beta
      receptors. Cultured CT cells from human inner ear periductal and perisaccular
      explant tissues were identified as fibroblasts. These cells compacted a three
      dimensional collagen lattice by a process that could be promoted by PDGF-BB, a
      factor involved in interstitial fluid pressure regulation. Our results are
      compatible with the notion that the periductal CT cells are involved in the
      regulation of inner ear fluid pressure. By active compaction of the periductal CT
      and by the formation of villous structures, the CT cells could modulate fluid
      fluxes over the ED epithelium as well as the longitudinal flow of endolymph in
      the ED.

PMID- 16408169
TI  - [Diclofenac during prostate needle biopsy. Significant pain reduction].
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of diclofenac to
      reduce pain during prostate biopsy. METHODS: After prospective randomization all
      patients received an intrarectal lidocaine gel instillation. Group 1 (n=80)
      functioned as control group, group 2 (n=72) received a placebo, and group 3
      (n=76) a 50 mg diclofenac suppository in addition. Patients were asked to
      identify their pain score (VAS 10) after the biopsy. Two weeks later, the
      patients were called and asked about the post-biopsy course. RESULTS: Patients in
      the diclofenac group had significantly lower pain scores than control or placebo
      group patients. Another biopsy without additional anesthesia was refused by 25%
      of the control group and 34% of the placebo group, but only by 11% of the
      diclofenac group (p<0.05). CONCLUSIONS: The preinterventional administration of
      diclofenac suppositories is a simple but efficient procedure for pain reduction
      in patients who undergo prostate biopsy.

PMID- 16408170
TI  - [Pitfalls and special features of modern imaging diagnostics of the upper
      cervical spine].
AB  - Recent technical developments led to a change in the significance of the
      different imaging modalities in the whole spectrum of neuroradiology and thus
      also in the field of imaging of the cervical spine. The main part in diagnostic
      imaging of the upper cervical spine is taken by high-resolution multislice CT and
      MRI. Conventional X-rays serve as an initial screening technique if required.

PMID- 16408171
TI  - Thermal sensation and thermophysiological responses to metabolic step-changes.
AB  - This study investigated the effect on thermal perception and thermophysiological
      variables of controlled metabolic excursions of various intensities and
      durations. Twenty-four subjects were alternately seated on a chair or exercised
      by walking on a treadmill at a temperature predicted to be neutral at sedentary
      activity. In a second experimental series, subjects alternated between rest and
      exercise as well as between exercise at different intensities at two temperature
      levels. Measurements comprised skin and oesophageal temperatures, heart rate and
      subjective responses. Thermal sensation started to rise or decline immediately
      (within 1 min) after a change of activity, which means that even moderate
      activity changes of short duration affect thermal perceptions of humans. After
      approximately 15-20 min under constant activity, subjective thermal responses
      approximated the steady-state response. The sensitivity of thermal sensation to
      changes in core temperature was higher for activity down-steps than for up-steps.
      A model was proposed that estimates transient thermal sensation after metabolic
      step-changes. Based on predictions by the model, weighting factors were suggested
      to estimate a representative average metabolic rate with varying activity levels,
      e.g. for the prediction of thermal sensation by steady-state comfort models. The
      activity during the most recent 5 min should be weighted 65%, during the prior 10
      5 min 25% and during the prior 20-10 min 10%.

PMID- 16408172
TI  - Who is the Silverman of Caffey-Silverman disease?

PMID- 16408173
TI  - Interventional radiology: a modular approach.
AB  - The authors offer a modular approach to the development of new procedures in the
      field of pediatric interventional radiology as a conceptual model and a
      springboard for further discussion.

PMID- 16408174
TI  - Cellulase production by Penicillium echinulatum on lactose.
AB  - The inducer effect of lactose on cellulase activity in Penicillium echinulatum
      9A02S1 was studied. Submerged cultivation was performed using different
      concentrations of lactose and cellulose, in which the pH, mycelial mass, soluble
      proteins, filter paper activity (FPA), and activity of beta-glucosidases were
      measured. The cultures containing lactose only presented low FPAs (0.1 FPU/ml).
      The cultures with associated cellulose and lactose and those containing cellulose
      only presented similar enzymatic activities (1.5 FPU/ml), suggesting the
      possibility of up to 75% reduction in the cellulose concentration. In relation to
      the beta-glucosidases, increasing the lactose/cellulose ratio results in a
      proportional increase of enzymatic activity. In the cultures using both inducers,
      there is a longer duration of the acid phase in relation to treatments using only
      cellulose or lactose, indicating diauxia and catabolic repression.

PMID- 16408175
TI  - Heterologous expression and characterization of a novel branching enzyme from the
      thermoalkaliphilic anaerobic bacterium Anaerobranca gottschalkii.
AB  - The gene encoding the branching enzyme (BE) from the thermoalkaliphilic,
      anaerobic bacterium Anaerobranca gottschalkii was fused with a twin arginine
      translocation protein secretory-pathway-dependent signal sequence from
      Escherichia coli and expressed in Staphylococcus carnosus. The secreted BE was
      purified using hydrophobic interaction and gel filtration chromatography. The
      monomeric enzyme (72 kDa) shows maximal activity at 50 degrees C and pH 7.0. With
      amylose the BE displays high transglycosylation and extremely low hydrolytic
      activity. The conversion of amylose and linear dextrins was analysed by applying
      high-performance anion exchange chromatography and quantitative size-exclusion
      chromatography. Amylose (10(4)-4 x 10(7) g/mol) was converted to a major extent
      to products displaying molecular masses of 10(4)-4 x 10(5) g/mol, indicating that
      the enzyme could be applicable for the production of starch or dextrins with
      narrow molecular mass distributions. The majority of the transferred
      oligosaccharides, determined after enzymatic hydrolysis of the newly synthesized
      alpha-1,6 linkages, ranged between 10(3) and 10(4) g/mol, which corresponds to a
      degree of polymerisation (DP) of 6-60. The minimal donor chain length is DP 16.
      Furthermore, the obtained results support the hypotheses of a random endocleavage
      mechanism of BE and the occurrence of interchain branching.

PMID- 16408176
TI  - Molecular characterization of grapevine plants transformed with GFLV resistance
      genes: II.
AB  - A collection of 127 putatively transgenic individuals of Vitis vinifera cv.
      Russalka was characterized by PCR and Southern hybridization. Six different
      constructs containing the neomycin phosphotransferase (nptII) marker gene and
      sequences of the Grapevine Fanleaf Virus Coat Protein (GFLV CP) gene including
      non-translatable and truncated forms were transferred via Agrobacterium-mediated
      transformation. Detection of transgenic sequences by PCR was positive in all
      lines. Southern blot analysis revealed that the number of inserted T-DNA copies
      ranged from 1 to 6. More than 46% of the tested transgenic lines contain one copy
      of the inserted T-DNA, qualifying them as interesting candidates for further
      breeding programs. Southern data of one line indicate the presence of an
      incomplete copy of the T-DNA, thus confirming previous PCR results. Since many
      putative transgenic lines shared identical hybridization patterns, they were
      clustered into 39 lines and considered as having originated from independent
      transformation events. The detection of the tetracycline (TET) resistance genes
      in 15% of the lines shows that an integration of plasmid backbone sequences
      beyond the T-DNA borders occurred. Enzyme-linked immunosorbent assay (ELISA)
      performed on leaf tissue did not show any accumulation of the GFLV CP in the 39
      transgenic lines analyzed. Reverse transcription polymerase chain reaction (RT
      PCR) and Northern blot were carried out; RT-PCR analyses showed that the GFLV CP
      mRNA was expressed at variable levels.

PMID- 16408178
TI  - Exogenous and endogenous growth regulators on apogamy in Dryopteris affinis
      (Lowe) Fraser-Jenkins sp. affinis.
AB  - This work showed for the first time the relationship between the effect of
      exogenous auxins and gibberellins on apogamy in Dryopteris affinis (Lowe) Fraser
      Jenkins sp. affinis and its endogenous contents during early apogamic events. The
      addition of NAA (0.53 and 5.37 microM) or GA(3) 2.8 microM to an MS solid medium
      significantly increased apogamous sporophyte formation. BA induced brown callus
      that regenerated sporophytes in a hormone-free medium. The endogenous contents of
      GA(1), GA(3), GA(4), GA(7), GA(9) and IAA were determined by GC-MS in
      gametophytes cultured on MS solid medium, before and during early stages of
      apogamous embryo development. The accumulation of both GA(9) and IAA before
      embryo development was evident as high levels of GA(4) in the earliest analysed
      stage of embryo development and high levels of GA(3) in elongating shoots were
      found. The role of gibberellins on apogamy was also supported by data showing a
      decrease in the percentage of gametophytes developing embryos because of the
      addition of flurprimidol to the culture medium.

PMID- 16408177
TI  - A distinct type of cyclin D, CYCD4;2, involved in the activation of cell division
      in Arabidopsis.
AB  - The Arabidopsis genome encodes 10 D-type cyclins (CYCD); however, their
      differential role in cell cycle control is not well known. Among them, CYCD4;2 is
      unique in the amino acid sequence; namely, it lacks the Rb-binding motif and the
      PEST sequence that are conserved in CYCDs. Here, we have shown that CYCD4;2
      suppressed G1 cyclin mutations in yeast and formed a kinase complex with CDKA;1,
      an ortholog of yeast Cdc28, in insect cells. Hypocotyl explants of CYCD4;2 over
      expressing plants showed faster induction of calli than wild-type explants on a
      medium containing lower concentration of auxin. These results suggest that
      CYCD4;2 has a promotive function in cell division by interacting with CDKA;1
      regardless of the unusual primary sequence.

PMID- 16408179
TI  - Tobacco ribosomal DNA spacer element elevates Bowman-Birk inhibitor expression in
      tomato plants.
AB  - Amplification promoting sequence (aps), from tobacco rDNA, was found to induce
      amplification and enhances the expression of heterologous genes, consequently
      increasing the expression of transgenic proteins in tobacco. In this report we
      demonstrate that aps element also affects integration, transcription, and
      translation of a soybean protease inhibitor, Bowman-Birk inhibitor (BBI), in
      transgenic tomato plants and quantifies its effects in different expression
      vectors. A synthetic bbi gene was constructed, based on the wild-type gene
      containing two independent inhibition sites; trypsin and chymotrypsin.
      Transformation vectors were designed using two different promoters; the tomato
      fruit specific E8 promoter and the constitutively active 35S CaMV promoter. These
      vectors were transformed into 'Moneymaker' tomato plants. In tomato fruits and
      leaves, aps caused a 3-fold increase in bbi mRNA levels when compared to the
      lines without aps. Similar increases were obtained in plants expressing bbi
      controlled by E8 or 35S CaMV promoters. Also, the level of BBI protein expression
      in aps-transformed plants was 3 fold-higher than in plants without aps. This is
      the first report of aps effect on the enhanced gene expression and transgenic
      protein production in plant other than tobacco.

PMID- 16408180
TI  - Gestational intestinal obstruction: a case report and review of literature.
AB  - Intestinal obstruction in pregnancy is rare and difficult to diagnose. Common
      causes of gestational intestinal obstruction include adhesions, volvulus,
      intussuscetion, carcinoma, hernia and appendicitis [3]. Abdominal pain is a
      common feature, but the displacement of abdominal organs as pregnancy progresses
      results in atypical location of the pain and hence delay in diagnosis. We report
      a case of intestinal obstruction at 33 weeks gestation in a woman with previous
      appendicectomy. Clinical suspicion of the presence of obstruction is required for
      prompt diagnosis and aggressive intervention, to minimise the morbidity and
      mortality of this rare complication of pregnancy.

PMID- 16408182
TI  - Transvaginal repair of a vesico-vaginal fistula using a mobilised vaginal flap to
      form the bladder base: a case report.
AB  - We describe a case of a vesico-vaginal fistula in a 32-year-old lady presenting
      with true urinary incontinence. There was a 1.5 x 1.5 cm deficit in the bladder
      wall and the left ureteric orifice was very close to the edge of the defect. For
      a successful transvaginal repair, we used a mobilized vaginal flap to bridge the
      defect in the bladder wall. This avoided the mobilization of the bladder wall and
      also prevented the left ureteric orifice from getting entrapped in the suture
      line. Adjacent wall of vagina was mobilized and stitched over the first layer to
      achieve water tight repair. Her post operative period was uneventful. The repair
      healed well and she was discharged in a good condition.

PMID- 16408181
TI  - Successful management of uterine incision hemorrhage in caesarean section with
      topical oxidized regenerated cellulose (Surgicel Nu Knit): a case report.
AB  - INTRODUCTION: Uterine hemorrhage is a common problem at the time of caesarean
      section especially in a repeat caesarean section and when the operation is
      performed for placenta praevia. CASE REPORT AND DISCUSSION: We present the case
      of a 28 year old woman undergoing a repeat emergency caesarean section for scar
      tenderness. She had excessive hemorrhage from the incision site that could not be
      controlled by traditional management including intravenous oxytocin and
      ergometrine, intramyometrial prostaglandin and local hemostatic sutures, but was
      successfully controlled with topical oxidized regenerated cellulose absorbable
      hemostat.

PMID- 16408183
TI  - Sedation for percutaneous treatment of hepatic hydatid cyst in a pregnant
      patient.
AB  - BACKGROUND: A 15 cm hepatic hydatid cyst was diagnosed in a multigravida in 16
      weeks of pregnancy and was managed percutaneously under sedation. RESULTS: No
      complication occurred and she gave birth to a healthy male baby after 37 weeks
      gestation.

PMID- 16408184
TI  - Decision-to-delivery interval for instrumental vaginal deliveries: vacuum
      extraction versus forceps.
AB  - OBJECTIVE: The aim of this study was to assess the decision-to-delivery interval
      for forceps delivery and vacuum extraction. STUDY DESIGN: A retrospective
      analysis of all instrumental deliveries over a 1-year period in a delivery ward
      of a university tertiary health care facility was performed. The decision-to
      delivery interval was compared between forceps delivery and vacuum extraction.
      RESULTS: The decision-to-delivery interval was 8.6+/-5.4 and 13.8+/-6.2 min for
      forceps and vacuum deliveries, respectively (P=0.0001). CONCLUSION: It appears
      that it is quicker to accomplish forceps delivery than vacuum extraction.

PMID- 16408185
TI  - Abdominal vs vaginal hysterectomy: a comparative study of the postoperative
      quality of life and satisfaction.
AB  - OBJECTIVE: To compare the short-term results of the quality of life and
      satisfaction of patients submitted to total abdominal hysterectomy (TAH) and
      vaginal hysterectomy (VH) for benign uterine disease. METHODS: Women referred for
      hysterectomy for uterine myoma were randomized to TAH (n=30) or VH (n=30). The
      exclusion criteria were uterine prolapse, indication associated surgical
      procedures and uterine size > or =300 cm3. After a month, follow-up
      questionnaires had a response rate of 100%, and consisted of an interview with
      application of SF-36 questionnaire (functional capacity, physical aspect and
      pain) and evaluation of satisfaction rate. RESULTS: There were no differences in
      the patients' mean age, parity, body mass index, preoperative hemoglobin levels
      and uterine size between groups. Lower postoperative quality-of-life scores were
      found in the TAH group when compared to the VH group in functional capacity
      (P=0.002), physical aspect (P=0.008) and pain (P=0.002). The general satisfaction
      rate with the surgery was similar in the two groups of patients (P=0.147).
      However, a higher rate of patients submitted to VH would choose the same
      therapeutic modality (65.5 vs 90%; P=0.021). CONCLUSIONS: A better postoperative
      quality of life (functional capacity, physical aspect and pain) and higher
      satisfaction rate was found in the VH when compared to TAH.

PMID- 16408187
TI  - Family members serving the gestational carrier needs of women lacking a uterus: a
      report of two cases.
AB  - CASE REPORT: In two instances, a designated relative served as a gestational
      carrier for a woman who no longer had a uterus. In the first case, a 38-year-old
      woman underwent an emergency cesarean hysterectomy due to worsening fatty
      degeneration of the liver in the third trimester, culminating in massive
      hemorrhage, consumptive coagulopathy and the loss of twins at 28 weeks gestation
      following successful in vitro fertilization. In the second case, a 28-year-old
      had congenital absence of the uterus and vagina. Both surrogates volunteered for
      service and were carefully screened medically, reproductively, and psychosocially
      prior to proceeding. All parties were required to execute informed consent and
      contracts with private attorneys before entry. Both gestational carriers
      conceived following the initial embryo transfer; one as the result of previously
      cryopreserved embryos, the other from embryos obtained following the synchronized
      in vitro fertilization of newly aspirated oocytes. Gestational carriers were
      prescribed oral estradiol and vaginal progesterone to prepare the uterus for
      implantation, and maintained this regimen throughout the first trimester of
      pregnancy. The pregnancies proceeded uneventfully and resulted in the delivery of
      singleton births at term. Both infants were formally adopted after delivery by
      the genetic parents in compliance with the advice of counsel under New York State
      law. CONCLUSION: Family members serving as gestational carriers provide women
      with functional ovaries but no uterus, the opportunity to have genetic offspring,
      while avoiding much of the high cost and social uncertainty of commercial
      surrogates.

PMID- 16408186
TI  - A case of torsion of a mucinous cystadenoma in triple-X syndrome with pure
      gonadal dysgenesis.
AB  - Triple-X female characterized by primary amenorrhea and pure gonadal dysgenesis
      is extremely rare. We present a patient of triple-X syndrome who has not had
      menarche or the development of the secondary sexual characteristics. She had a
      hypoplastic uterus and streaked gonads on both sides with a twisted mucinous
      cystadenoma in the right adnexa.

PMID- 16408188
TI  - Ultrasound in obstetrics: are we getting too good?

PMID- 16408189
TI  - Vascular endothelial growth factor response to exogenous chorionic gonadotropic
      hormone in the luteal phase of women with a history of severe ovarian
      hyperstimulation syndrome.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a severe complication of ovarian
      stimulation. No reliable test exists to predict the syndrome. The objective of
      the present prospective observational study was to examine vascular endothelial
      growth factor (VEGF) secretion after human chorionic gonadotropin (hCG)
      administration in the luteal phase of a spontaneous cycle of women with a history
      of severe OHSS. Five women with a history of severe OHSS were administered 250
      mug recombinant hCG intravenously on day 21 of a spontaneous menstrual cycle.
      Plasma samples were collected at regular intervals from 15 min before hCG to 6 h
      thereafter and the free VEGF plasma concentrations were determined. Plasma levels
      of free VEGF remained at the lower detection limit of the assay throughout the
      observational period. Women with previous severe OHSS do not show a significant
      short-time response of VEGF secretion upon hCG administration. No evidence was
      found to support the notion that women inclined to develop a severe form of the
      syndrome after ovarian stimulation could possibly be identified by the VEGF short
      time secretory response to exogenous hCG in the luteal phase of a spontaneous
      cycle.

PMID- 16408190
TI  - Small-scale domestic wastewater treatment using an alternating pumped sequencing
      batch biofilm reactor system.
AB  - An alternating pumped sequencing batch biofilm reactor (APSBBR) system was
      developed to treat small-scale domestic wastewater. This laboratory system had
      two reactor tanks, Reactor 1 and Reactor 2, with two identical plastic biofilm
      modules in each reactor. Reactor 1 of the APSBBR had five operational phases-
      fill, anoxic, aerobic, settle and draw. In the aerobic phase, the wastewater was
      circulated between the two reactor tanks with centrifugal pumps and aeration was
      mainly achieved through oxygen absorption by microorganisms in the biofilms when
      they were exposed to the air. This paper details the performance of the APSBBR
      system in treating synthetic domestic wastewater over 18 months. The effluent
      from the APSBBR system satisfied the European Wastewater Treatment Directive
      requirements, with respect to COD, ammonium-nitrogen and suspended solids. The
      biofilm growth in the two reactor tanks was different due to the difference in
      substrate loadings and growth conditions.

PMID- 16408191
TI  - Optimization of free ammonia concentration for nitrite accumulation in shortcut
      biological nitrogen removal process.
AB  - A shortcut biological nitrogen removal (SBNR) utilizes the concept of a direct
      conversion of ammonium to nitrite and then to nitrogen gas. A successful SBNR
      requires accumulation of nitrite in the system and inhibition of the activity of
      nitrite oxidizers. A high concentration of free ammonia (FA) inhibits nitrite
      oxidizers, but unfortunately decreases the ammonium removal rate as well.
      Therefore, the optimal range of FA concentration is necessary not only to
      stabilize nitrite accumulation but also to achieve maximum ammonium removal. In
      order to derive such optimal FA concentrations, the specific substrate
      utilization rates of ammonium and nitrite oxidizers were measured. The optimal FA
      concentration range appeared to be 5-10 mg/L for the adapted sludge. The
      simulated results from the modified inhibition model expressed by FA and
      ammonium/nitrite concentrations were shown very similar to the experimental
      results.

PMID- 16408192
TI  - Plasminogen activators and their inhibitor gene expression in cutaneous NF1
      related neurofibromas.
AB  - Cutaneous neurofibromatosis 1 (NF1)-related neurofibromas are benign tumors and
      composed of Schwann cells, perineurial cells and/or fibroblasts, endothelial
      cells, mast cells and macrophages. Extracellular proteolysis namely plasminogen
      activation (PA) operates in many tissue destructive processes. We wanted to study
      plasminogen activators, urokinase (uPA) and tissue type (tPA) and their inhibitor
      PAI-1, which have not earlier been studied comprehensively in cutaneous NF1
      related tumors. We analyzed the distribution of uPA, tPA and PAI-1 antigen level
      by immunohistochemistry and mRNA level by in situ hybridization, to identify
      which cells are primarily involved in proteolytic activity and plasminogen
      activation. Twelve NF1 skin tumor samples from six patients were obtained during
      the operations. Mast cells, macrophages and endothelial cells were distributed
      only locally. Their expression levels of PA components were not so notable. Large
      extent of tumor cells of Schwann cell origin and prominent expression levels of
      uPA, tPA and PAI-1 indicated that these cells are responsible for the main source
      of PA components in cutaneous NF1-related neurofibromas.

PMID- 16408193
TI  - The sick building syndrome: a chicken and egg situation?
AB  - OBJECTIVES: To examine the temporal relationship and specificity between self
      reports on the indoor environment at work and symptoms that are traditionally
      connected with the sick building syndrome (SBS). METHODS: This questionnaire
      study used a prospective full panel design as regards self-reports on exposure
      and outcome. At the baseline, the sample comprised 2,164 adults selected randomly
      from the general population. Of these 1,402, who were still working and living in
      the same place, completed a second questionnaire a year later. Health measures
      were symptoms that are traditionally connected with the SBS, as well as some
      "dummy" symptoms that hardly can be causally related to the indoor environment.
      The associations between self-reports on the indoor environment and these symptom
      groups were assessed both in cross-sectional and longitudinal analyses, the
      latter examining the normal direction that exposure leads to symptoms as well as
      the reverse order: that symptoms lead to perceived exposure. RESULTS: In cross
      sectional analyses, the indoor environment factors were associated equally with
      SBS symptoms and with "dummy" symptoms. In longitudinal analyses, only few of the
      indoor environment factors predicted the development of any of the symptom
      groups. However, both the SBS symptoms and the "dummy" symptoms were risk factors
      for beginning to report exposures in the indoor environment. CONCLUSIONS:
      Symptoms predict future reports on exposures in the indoor environment indicating
      that it is difficult to determine what existed first: the outcome or the
      exposure. In addition, the perceived indoor environment is associated not only
      with the traditional SBS symptoms, but also with symptoms that cannot be
      physiologically linked to the indoor environment. These results suggest that
      there is a risk of reporting bias when assessing non-specific symptoms. Thus,
      many of the associations found in previous cross-sectional studies on SBS
      symptoms and indoor environment factors may possibly be explained by reporting
      bias.

PMID- 16408194
TI  - Correlation among cadmium levels in river sediment, in rice, in daily foods and
      in urine of residents in 11 prefectures in Japan.
AB  - OBJECTIVE: The objective of this study is to examine if overall correlation
      exists among cadmium levels (Cd) in the general environment, dietary Cd intake,
      and Cd body burden of local residents. METHODS: Eleven prefectures in Japan were
      selected as the areas where large-scale data on Cd levels in urine of adult women
      (40-49 and 50-59 years of age, respectively) were available to calculate
      geometric mean (GM) values for each of the prefecture. Other data were cited from
      published or previously established databases on Cd in the sediments of river
      bottoms (as a representative of Cd in the environment), Cd in rice for local
      consumption, and Cd in daily food duplicate samples collected from local women
      populations, and calculated for GM values for the prefectures. The GM values were
      subjected to correlation matrix and regression analysis. RESULTS: Marginally
      significant (P < 0.10) correlation was detected between Cd in sediment and Cd in
      rice. Furthermore, correlation of Cd in sediment was significant with Cd in total
      foods (P < 0.05) and possibly with Cd in urine (P < 0.05-0.10). Importance of
      data on Cd in rice paddy soil as a missing link is discussed. CONCLUSIONS:
      Correlation was demonstrated in the flow of Cd transport from the environment
      (expressed as Cd contents in river sediments) to humans (in terms of Cd in urine)
      among general populations in Japan.

PMID- 16408195
TI  - GABAergic lineage differentiation of AF5 neural progenitor cells in vitro.
AB  - We have previously described an immortal rat central-nervous-system progenitor
      cell line, AF5, which is able to exit the cell cycle and assume a differentiated
      state with neuronal properties. The phenotypic specification of differentiated
      AF5 cells, however, is not known. In the present study, when induced to
      differentiate by serum starvation in Neurobasal medium, AF5 cells down-regulate
      glial fibrillary acidic protein and up-regulate expression of beta-III-tubulin,
      medium-molecular-weight neurofilament protein, and neuronal growth-associated
      protein 43. Expression of the gamma-aminobutyric acid (GABA) lineage marker,
      glutamic acid decarboxylase 67 (GAD67), increases during differentiation,
      suggesting that AF5 cells adopt a GABAergic lineage. Time-course analysis of the
      GABAergic neuron specification transcription factor, Pitx2, by reverse
      transcription/polymerase chain reaction, has shown an increase in the Pitx2
      transcript 48 h after initiation of differentiation. In differentiated AF5 cells,
      expression of the Pitx2 target gene products GAD65 and GABA transporter-1
      increases. Cellular GABA levels in differentiated AF5 cells increase by about 26
      fold, and GABA release into the medium is 150-fold higher compared with that of
      undifferentiated cells. Therefore, AF5 cells can be induced to differentiate to a
      neuronal phenotype with a GABAergic lineage.

PMID- 16408196
TI  - mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching.
AB  - The present study has aimed to verify the influence of calcineurin and mTOR
      pathways in skeletal muscle longitudinal growth induced by stretching. Male
      Wistar rats were treated with cyclosporin-A or rapamycin for 10 days. To promote
      muscle stretching, casts were positioned so as completely to dorsiflex the
      plantar-flexor muscles at the ankle in one hind limb during the last 4 days of
      treatment with either cyclosporin-A or rapamycin. Thereafter, we determined
      soleus length, weight, protein content, and phenotype. In addition, NFATc1,
      Raptor, S6K1, 4E-BP1, iNOS, and nNOS gene expression in the soleus were
      determined by real-time polymerase chain reaction. Soleus length, weight, and
      protein content were significantly reduced by rapamycin treatment in animals
      submitted to stretching (P<0.05). In contrast, cyclosporin-A treatment did not
      alter these parameters. In all cyclosporin-A treated groups, there was a
      significant reduction in NFATc1 expression (P<0.001). Similarly, a significant
      reduction was noted in Raptor (P<0.001) and S6K1 (P<0.01) expression in all
      rapamycin-treated groups. No alteration was observed in 4E-BP1 gene expression
      among rapamycin-treated groups. Stretching increased gene expression of both NOS
      isoforms in skeletal muscle. Rapamycin treatment did not interfere with NOS gene
      expression (P<0.05). Cyclosporin-A treatment did not impair muscle growth induced
      by stretching but instead caused a marked slow-to-fast fiber shift in the soleus;
      this was attenuated by stretching. The data presented herein indicate that mTOR
      pathway is involved in skeletal muscle longitudinal growth.

PMID- 16408198
TI  - Compatible invasion of a phylogenetically distant host embryo by a hymenopteran
      parasitoid embryo.
AB  - Embryonic invasion into the tissue of genetically different organisms has been
      known only in mother-embryo interactions of viviparous organisms. Hence,
      embryonic invasions have been thought to occur only within the same or closely
      related species. For endoparasitic Hymenoptera, which are oviposited in their
      host egg but complete their development in the later stages, entry into the host
      embryo is essential. To date, the entry of these parasitoids is known to be
      accomplished by either egg deposition directly into the embryo or by the newly
      hatched larva boring into the embryo. However, Copidosoma floridanum is a
      polyembryonic parasitoid whose development is characterized by a prolonged
      embryonic stage, and which lacks a larval form during its host embryogenesis. We
      have analyzed the behavior and fate of C. floridanum embryos co-cultured with
      their host embryo in vitro. Here, we show that the morula-stage embryo of C.
      floridanum actively invades the host embryo. Histological analyses have
      demonstrated that C. floridanum embryonic invasion is associated with adherent
      junction to host cells rather than causing an obvious wound on the host cells.
      These findings provide a novel case of embryonic invasion into a phylogenetically
      distant host embryo, ensuring cellular compatibility with host tissues.

PMID- 16408197
TI  - Identification of the lacZ insertion site and beta-galactosidase expression in
      transgenic chickens.
AB  - The quail:chick chimera system is a classical research model in developmental
      biology. An improvement over the quail:chick chimera system would be a line of
      transgenic chickens expressing a reporter gene. Transgenic chickens carrying lacZ
      and expressing bacterial beta-galactosidase have been generated, but complete
      characterization of the insertion event and characterization of beta
      galactosidase expression have not previously been available. The genomic
      sequences flanking the retroviral insertion site have now been identified by
      using inverse polymerase chain reaction (PCR), homozygous individuals have been
      identified by using PCR-based genotyping, and beta-galactosidase expression has
      been evaluated by using Western analysis and histochemistry. Based upon the
      current draft of the chicken genome, the viral insertion carrying the lacZ gene
      has been located on chromosome 11 within the predicted gene for
      neurotactin/fractalkine (CX3CL1); neurotactin mRNA expression appears to be
      missing from the brain of homozygous individuals. When Generation 2 (G2) lacZ
      positive individuals were inter-mated, they generated 361 G3 progeny; 82 were
      homozyous for lacZ (22.7%), 97 were wild-type non-transgenic (26.9%), and 182
      (50.4%) were hemizygous for lacZ. Western analysis revealed the highest
      expression in the muscle and liver. With the identification of homozygous birds,
      the line of chickens is now designated NCSU-Blue1.

PMID- 16408199
TI  - Diversity of CD97 in smooth muscle cells.
AB  - CD97, an epidermal growth factor (EGF)-TM7 receptor, is not restricted to
      hematopoetic and carcinoma cells but is also found on smooth muscle cells (SMC).
      We have examined its location and biochemical structure in various normal and
      tumorigenic SMC-containing tissues. SMC of the urinary bladder, lung bronchi and
      bronchioles, myometrium, and gastrointestinal tract were immunohistologically
      stained by using monoclonal antibodies (mabs) to the CD97 stalk region
      (CD97(stalk)). Mabs directed against an N-glycosylation-dependent epitope within
      the EGF-domains (CD97(EGF)) did not bind to normal SMC. Vascular SMC, which was
      also CD97(EGF)-negative, showed further CD97 heterogeneity. Only a few, if any,
      SMC from the aorta or elastic arteries of the systemic circulation were positive
      for CD97 mRNA and therefore also for CD97(stalk). CD97(stalk)-positive SMC were
      slightly more numerous in muscular and peripheral arteries. In contrast, most
      venous SMC expressed CD97(stalk). A comparison with other SMC molecules revealed
      a similar but not identical staining pattern for CD97(stalk) and desmin. Further
      CD97 heterogeneity was observed during SMC transformation. All leiomyomas (n=5)
      and nine out of 21 leiomyosarcomas were positive for both CD97(stalk) and
      CD97(EGF). As expected, CD97(EGF)-positive SMC tumors expressed partly N
      glycosylated CD97. Seven out of 21 leiomyosarcomas were completely devoid of
      CD97. Thus, CD97 showed variable expression in vascular and biochemical
      modification in tumorigenic SMC, suggesting that the function of the molecule is
      specific for the SMC subtype.

PMID- 16408200
TI  - Establishing and characterizing human periodontal ligament fibroblasts
      immortalized by SV40T-antigen and hTERT gene transfer.
AB  - The periodontal ligament (PDL) is a highly specialized tissue connecting the
      cementum with the tooth socket bone and affects the life span of the tooth.
      However, little is known about the precise characteristics and regenerative
      mechanism of PDL cells because of the absence of specific markers and cell lines.
      Therefore, we aimed to establish three immortalized human PDL fibroblast cell
      lines by using simian virus40 T-antigen (SV40T-Ag) and human telomerase reverse
      transcriptase (hTERT) transfection, expecting these cells to have the
      characteristics of primary cells. The transfected cells were named STPLF. The
      expression of SV40T-Ag and hTERT in all STPLF lines was verified by using the
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      method, stretch PCR analysis, or Western blotting analysis. All STPLF showed
      stable proliferation at more than 120 population doublings (PD), whereas primary
      human PDL fibroblasts (HPLF) stopped at 10-20 PD. Characterization by RT-PCR
      analysis revealed that all STPLF genes mimicked the expression of their
      respective original HPLF genes. STPLF expressed runt-related transcription factor
      2, osterix, alkaline phosphatase, osteopontin, osteocalcin, periostin, receptor
      activator of NF-kappa B ligand, osteoprotegerin, epidermal growth factor
      receptor, alpha-smooth muscle actin, and type XII collagen. STPLF stimulated with
      50 micro g/ml ascorbic acid and 2 mM beta-glycerophosphate for 4 weeks produced
      more calcified deposits than did HPLF cultured with the same reagents. These
      results suggest that each STPLF line retained the characteristics of the
      respective original HPLF, that STPLF gained increased calcification activity, and
      that STPLF are helpful tools for studying the biology and regenerative mechanisms
      of human PDL.

PMID- 16408201
TI  - Short TE quantitative proton magnetic resonance spectroscopy in variant
      Creutzfeldt-Jakob disease.
AB  - Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder.
      Clinical diagnosis is difficult in the early stages as the disease often presents
      with non-specific psychiatric and neurological symptoms. To investigate the
      diagnostic potential of quantitative short TE in vivo MRS, and the nature and
      anatomical distribution of biochemical abnormalities in vCJD, localised single
      voxel spectra (TE/TR 30 ms/2,000 ms) were acquired from three brain regions:
      thalami, caudate nuclei and frontal white matter. Metabolite concentrations and
      ratios from three patients with definite or probable vCJD were compared with
      eight normal age-matched controls. Abnormal signal on T2-weighted MRI was
      apparent in the pulvinar region in all vCJD patients; this region also showed
      greatly increased myo-inositol [MI] (mean 2.5-fold, P=0.01) and decreased N
      acetyl-aspartate (NAA; mean 2-fold, P=0.01). Two patients also showed increased
      [MI] (z=17, 11; one with decreased NAA, z=-12) in normal-appearing caudate
      nuclei. The magnitude of metabolite abnormalities in the thalami in moderately
      advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols
      allow the measurement of MI, which adds discriminant power to the MRS
      examination.

PMID- 16408202
TI  - Intracavernous fenestration of the internal carotid artery.

PMID- 16408203
TI  - Phase II trial of intravenous lobradimil and carboplatin in childhood brain
      tumors: a report from the Children's Oncology Group.
AB  - BACKGROUND: [corrected] Lobradimil is a synthetic bradykinin analog that rapidly
      and transiently increases the permeability of the blood-brain barrier (BBB). The
      combination of lobradimil and carboplatin was studied in pediatric patients with
      primary brain tumors in a phase II trial, the primary endpoints of which were to
      estimate the response rate and time to disease progression. PATIENTS AND METHODS:
      Patients were stratified by histology into five cohorts: brainstem glioma, high
      grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor
      (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve
      a target AUC of 3.5 mg min/ml per day (7 mg.min/ml/cycle) intravenously over 15
      min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2
      consecutive days each 28 day cycle. RESULTS: Forty-one patients, age 2-19 years,
      were enrolled; 38 patients, including 1 patient ultimately determined to have
      atypical neurocytoma, were evaluable for response. No objective responses were
      observed in the brainstem glioma (n=12) and high-grade glioma (n = 9) cohorts,
      although two patients with high-grade glioma had prolonged disease stabilization
      (>6 months). The study was closed for commercial reasons prior to achieving the
      accrual goals for the ependymoma (n = 8), medulloblastoma/PNET (n = 6) and low
      grade glioma (n = 2) cohorts, although responses were observed in 1 patient with
      PNET and 2 patients with ependymoma. CONCLUSION: The combination of lobradimil
      and carboplatin was inactive in childhood high-grade gliomas and brainstem
      gliomas.

PMID- 16408204
TI  - The cytotoxic and genotoxic potential of 5-aminolevulinic acid on lymphocytes: a
      comet assay study.
AB  - BACKGROUND: 5-aminolevulinic acid (ALA) and its hexylester (ALA-H) are the drugs
      currently used in photodynamic therapy (PDT). The side effect, especially the
      long-term side effect of these drugs is a problem of concern in this field, which
      has not been clearly understood yet. PURPOSE: The normal lymphocytes and
      nasopharyngeal carcinoma (NPC) cells were used as the cell models to evaluate the
      side effects of ALA or ALA-H in the absence of light or under sub-lethal doses of
      light. METHODS: The cytotoxic and DNA-damaging effects of ALA or ALA-H on
      lymphocytes and NPC cells were studied by means of the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay and the alkaline comet assay. ALA at
      0.75 mM concentration and ALA-H at 10-microM concentrations were selected in the
      studies. This is because under these concentrations, ALA- or ALA-H-mediated PDT
      can destroy most NPC cells in vitro. The intracellular distributions of the
      protoporphyrin IX (PpIX), induced by the ALA or ALA-H, were measured by the
      confocal laser scanning microscope to provide more information for understanding
      the DNA damage. RESULTS: The incubation of 0.75 mM ALA or 10 microM ALA-H alone
      (without light) did not cause DNA damage as well as the considerable cytotoxic
      effect on NPC cells. However, after ALA (0.75 mM) incubation and without light
      irradiation, the serious cytotoxicity and remarkable DNA damage were found in
      lymphocytes. When the lymphocytes were incubated with ALA-H (10 microM) alone (in
      the absence of light), no DNA damage could be detected and a slight cytotoxic
      effect was found. Both ALA and ALA-H induced PpIX in the lymphocytes. The
      fluorescence images of PpIX intracellular localization demonstrated that the PpIX
      diffused into the nuclear region in ALA-(0.75 mM)-incubated lymphocytes but not
      existed in the nucleus of ALA-H(10 microM)- incubated lymphocytes, providing an
      explanation for the facts that ALA (0.75 mM) induced the DNA damage while ALA-H
      (10 microM) did not. CONCLUSION: These results suggested that the genotoxic
      potential of lymphocytes seems high for ALA (0.75 mM) and could be excluded for
      ALA-H (10 microM).

PMID- 16408205
TI  - A proteomic approach to the identification and characterisation of protein
      composition in wheat germ.
AB  - Proteome analyses were carried out on commercial wheat germ of mature grain from
      the biscuit-making wheat cultivar, Rosella. Wheat germ protein extracts were
      fractionated by two-dimensional gel electrophoresis across two different
      immobilised pH gradients: pH 4.0-7.0 and 6.0-9.0. A total of 612 individual
      protein spots were excised from the gels and characterised by peptide mass
      fingerprinting. From these analyses, 347 individual proteins were identified from
      protein sequence database interrogation, and 301 different types of protein were
      catalogued according to protein function. The remaining 265 protein spots gave
      poor or no matches to proteins in the databases and were not identified in this
      study. Six different classes of enzymes were identified in the germ, many of them
      having roles in the mobilisation of energy reserves for germination. Abundantly
      expressed enzyme classes include the oxidoreductases, transferases and
      hydrolases. A comparison was also made between the major protein classes
      expressed in the germ and protein classes expressed in the endosperm from
      previous proteomic work. This study contributes significantly to our knowledge of
      protein expression and heterogeneity in the germ of wheat grain and forms the
      basis for future studies in regard to the characterisation of proteins during the
      initial stages of germination.

PMID- 16408206
TI  - Erythropoietin plus granulocyte colony-stimulating factor is better than
      erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes:
      results from a randomized single-centre study.
AB  - Haemopoietic growth factors (HGF), i.e. erythropoietin [recombinant human
      erythropoietin (rHEPO)] or granulocyte colony stimulating factor (G-CSF), alone
      or in combination, have largely been used to treat anemia in myelodysplastic
      syndromes (MDS), but whether combined rHEPO and G-CSF is really superior to rHEPO
      alone is still under debate. In particular, randomized studies comparing front
      line rHEPO vs rHEPO+G-CSF are still lacking. The aim of this study was to compare
      the effects of "standard" doses of rHEPO with the combination of rHEPO and G-CSF
      in the treatment of anemic patients with low-risk MDS in a prospective randomized
      trial. Anemic patients with low-risk MDS were randomly assigned to receive either
      rHEPO (10,000 IU s.c. three times a week) or the same dosage of rHEPO+G-CSF (300
      mug s.c. twice a week) for a minimum of 8 weeks. Patients who were unresponsive
      to rHEPO were offered the combination therapy for another 8 weeks, whereas non
      responders to rHEPO+G-CSF were considered "off study". Responders continued the
      treatment indefinitely. Both haematological response and changes in quality-of
      life (QoL) scores (Functional Assessment of Cancer Therapy-Anemia) were recorded
      and evaluated. Thirty consecutive patients [10 refractory anemia (RA), 5 RA with
      ringed sideroblasts, 7 refractory cytopenia with multilineage dysplasia, 5 RA
      with less than 10% blasts and 3 5q-syndrome] were enrolled in the study. All of
      them (15 in the rHEPO arm and 15 in the rHEPO+G-CSF arm) were valuable after the
      first 8 weeks of treatment. Erythroid response was observed in 6/15 (40%)
      patients in the rHEPO arm and in 11/15 (73.3%) patients in the rHEPO+G-CSF arm.
      In 4/9 (44.4%) patients who were unresponsive to rHEPO, the addition of G-CSF
      induced erythroid response at 16 weeks. No relevant adverse effects were recorded
      for either treatment in any of the study patients. Erythroid response to HGF was
      associated with a relevant improvement in QoL. Twenty responders continued the
      treatment. Afterwards, 8/20 (40%) discontinued therapy because of the following:
      losing response (2), progression to high-risk MDS (3) and death due to other
      causes (3). The remaining 12 are still responding and continuing treatment, with
      a median follow-up of 28 months. Progression to acute leukemia was cumulatively
      observed in 4/30 (13.3%) patients (2 in each arm). Although our data were
      obtained from a relatively small cohort of patients, they indicate that the
      rHEPO+G-CSF treatment is more effective than rHEPO alone for correcting anemia in
      low-risk MDS patients and for making a relevant improvement in their QoL.

PMID- 16408208
TI  - Mutation in a homolog of yeast Vps53p accounts for the heat and osmotic
      hypersensitive phenotypes in Arabidopsis hit1-1 mutant.
AB  - Previously, the growth of Arabidopsis hit1-1 (heat-intolerant) mutant was found
      to be inhibited by both heat and water stress (Wu et al. in J Plant Physiol
      157:543-547, 2000). In order to determine the genetic mutation underlying the
      hit1-1 phenotype, map-based cloning of HIT1 gene was conducted. Transformation of
      the hit1-1 mutant with a HIT1 cDNA clone reverts the mutant to the heat tolerance
      phenotype, confirming the identity of HIT1. Sequence analysis revealed the HIT1
      gene encodes a protein of 829 amino acid residues and is homologous to yeast
      (Saccharomyces cerevisiae) Vps53p protein. The yeast Vps53p protein has been
      shown to be a tethering factor that associates with Vps52p and Vps54p in a
      complex formation involved in the retrograde trafficking of vesicles to the late
      Golgi. An Arabidopsis homolog of yeast Vps52p has previously been identified and
      mutation of either the homolog or HIT1 by T-DNA insertion resulted in a male
      specific transmission defect. The growth of yeast vps53Delta null mutant also
      shows reduced thermotolerance, and expression of HIT1 in this mutant can
      partially complement the defect, supporting the possibility of a conserved
      biological function for Vps53p and HIT1. Collectively, the hit1-1 is the first
      mutant in higher plant linking a homolog of the vesicle tethering factor to both
      heat and osmotic stress tolerance.

PMID- 16408209
TI  - Identification and characterization of an Arabidopsis homogentisate
      phytyltransferase paralog.
AB  - Tocochromanols (tocopherols and tocotrienols) are micronutrients with antioxidant
      properties synthesized by photosynthetic bacteria and plants that play important
      roles in animal and human nutrition. There is considerable interest in
      identifying the genes involved in tocochromanol biosynthesis to allow transgenic
      modification of both tocochromanol levels and tocochromanol composition in
      agricultural crops. The first committed reaction in tocopherol biosynthesis is
      the condensation of homogentisic acid (HGA) with phytyldiphosphate or
      geranylgeranyldiphosphate, catalyzed by the homogentisate phytyltransferase
      (VTE2) or by the homogentisate geranylgeranyl transferase (HGGT). In this study,
      we describe the identification of conserved amino acid sequences within VTE2 and
      HGGT and the application of these conserved sequences for a motif analysis
      resulting in the discovery of a VTE2-paralog in the Arabidopsis genome. We
      designated this new gene VTE2-2 and renamed the old VTE2 to VTE2-1. Seed-specific
      expression of VTE2-2 in Arabidopsis resulted in increased seed-tocopherol levels,
      similar to the transgenic expression of VTE2-1. Bioinformatics analysis revealed
      that VTE2-2 is conserved in both monocotyledonous and dicotyledonous plants and
      is distinct from VTE2-1 and HGGT.

PMID- 16408211
TI  - Effect of interleukin-18 on metastasis of mouse osteosarcoma cells.
AB  - The effect of interleukin-18 (IL-18) on metastasis of highly metastatic LM8 mouse
      osteosarcoma cells was investigated using nude mice treated with anti-asialo GM1
      serum to exclude anti-tumor actions of IL-18 through activation of T and natural
      killer cells. Injection of LM8 cells which do not express IL-18 receptor beta
      into a tail vain resulted in the formation of pulmonary and hepatic metastatic
      foci. Daily injection of mice with IL-18 starting the fifth day from the cell
      injection had no significant effect on the number of metastatic foci, while five
      daily injections of IL-18 before and after the cell injection resulted in marked
      decreases. Culture of LM8 cells with IL-18 for 5 days before the injection into
      mice produced no significant effect on the number of pulmonary and hepatic
      metastatic foci. In contrast, pretreatment of mice with IL-18 for 5 days before
      the cell injection markedly decreased metastatic foci. The retention of LM8 cells
      in the lung 24 h after their injection was also reduced by the pretreatment of
      mice with IL-18. Serum obtained from mice pretreated with IL-18 for 5 days
      suppressed mobility of LM8 cells but IL-18 itself did not. These results suggest
      that IL-18 inhibits metastasis of LM8 cells partly by inducing a factor(s) in the
      host which suppresses cell mobility.

PMID- 16408210
TI  - Rapid depletion of mutant eukaryotic initiation factor 5A at restrictive
      temperature reveals connections to actin cytoskeleton and cell cycle progression.
AB  - Eukaryotic initiation factor 5A (eIF5A) is the only protein in nature that
      contains hypusine, an unusual amino acid derived from the modification of lysine
      by spermidine. Two genes, TIF51A and TIF51B, encode eIF5A in the yeast
      Saccharomyces cerevisiae. In an effort to understand the structure-function
      relationship of eIF5A, we have generated yeast mutants by introducing plasmid
      borne tif51A into a double null strain where both TIF51A and TIF51B have been
      disrupted. One of the mutants, tsL102A strain (tif51A L102A tif51aDelta
      tif51bDelta) exhibits a strong temperature-sensitive growth phenotype. At the
      restrictive temperature, tsL102A strain also exhibits a cell shape change, a lack
      of volume change in response to temperature increase and becomes more sensitive
      to ethanol, a hallmark of defects in the PKC/WSC cell wall integrity pathway. In
      addition, a striking change in actin dynamics and a complete cell cycle arrest at
      G1 phase occur in tsL102A cells at restrictive temperature. The temperature
      sensitivity of tsL102A strain is due to a rapid loss of mutant eIF5A with the
      half-life reduced from 6 h at permissive temperature to 20 min at restrictive
      temperature. Phenylmethyl sulfonylfluoride (PMSF), an irreversible inhibitor of
      serine protease, inhibited the degradation of mutant eIF5A and suppressed the
      temperature-sensitive growth arrest. Sorbitol, an osmotic stabilizer that
      complement defects in PKC/WSC pathways, stabilizes the mutant eIF5A and
      suppresses all the observed temperature-sensitive phenotypes.

PMID- 16408212
TI  - Fifth European progress in vaccination against cancer conference, PIVAC 5.

PMID- 16408213
TI  - The use of reverse immunology to identify HLA-A2 binding epitopes in Tie-2.
AB  - A potential target for a cancer vaccine would be receptors, such as Tie-2 which
      are over expressed on tumour endothelium. Using computer aided motif predictions
      for possible HLA class I epitopes, we have identified peptides from Tie-2 that
      should bind with a range of affinities to HLA-A*0201. No direct correlation
      between predicted values and actual binding affinities was observed. Although,
      the programs did produce a number of false positives, two epitopes were predicted
      that bound with relatively high affinity when compared with an influenza peptide.
      We have previously identified a Tie-2 epitope and shown that it was only
      immunogenic when we substituted preferred amino acids at key anchor residues to
      increase binding affinity. In this study we used a similar approach to generate
      modified epitopes. When HLA-A2 transgenic mice were immunised with peptides, CTL
      killing of the target cells was only achieved when the wild type epitope was
      presented at moderate levels. Moreover, the efficiency of immunisation was
      increased when we linked CD4 epitopes to CD8 epitopes. Caution should therefore
      be employed in the use of both reverse immunology and anchor modification of CTL
      epitopes in the identification of CTL epitopes for cancer vaccines.

PMID- 16408214
TI  - The anti-tumor efficacy of a GM-CSF-secreting tumor cell vaccine is not inhibited
      by docetaxel administration.
AB  - Docetaxel has demonstrated therapeutic efficacy against breast, prostate, and
      ovarian cancer and other solid tumors. The tumoricidal activity of docetaxel is
      mainly attributed to its ability to block microtubule depolymerization, thus
      inducing G(2)-M arrest and apoptosis. Mounting evidence indicates that docetaxel
      also possesses immunomodulatory activity such as augmenting macrophage and
      lymphokine activated killer activity and inducing pro-inflammatory cytokines,
      suggesting that docetaxel may be a good chemotherapeutic agent to combine with
      cancer immunotherapies, assuming that it does not inhibit the vaccine-induced
      immune response. The anti-tumor activity of the combination of docetaxel and a GM
      CSF-secreting B16F10 tumor cell vaccine (B16.GM) was evaluated in the murine B16
      melanoma model. Dose levels of docetaxel and the B16.GM vaccine known to be
      ineffective when used as single agents were selected. Three iv treatments of 6
      mg/kg docetaxel per injection given on days 5, 9, and 13 after tumor challenge or
      a single vaccination with 2-3 x 10(6) B16.GM cells on day 3 were ineffective at
      inhibiting tumor growth when used as single agents [median survival time (MST)=24
      days in both treatment groups and in control animals]. However, combination of
      docetaxel and B16.GM vaccine significantly delayed tumor growth, increasing MST
      to 45 days. A similar improvement in anti-tumor efficacy was observed using
      multiple treatment cycles of the B16.GM vaccine/docetaxel combination.
      Administration of docetaxel every 4 days between bi-weekly B16.GM vaccinations
      increased the median survival of tumor-bearing mice from 31 to 52 days compared
      to multiple B16.GM vaccinations alone. In summary, these data demonstrate that
      rather than inhibiting the anti-tumor effects of a GM-CSF-secreting tumor cell
      vaccine, docetaxel combined with a whole cell vaccine significantly inhibits
      tumor growth, increases survival time and does not impede T-cell activation in
      the murine B16F10 melanoma tumor model. GM-secreting tumor cell vaccines in
      combination with docetaxel may represent a new strategy for combining chemo and
      immunotherapy for cancer.

PMID- 16408216
TI  - Fluidized beds in flow analysis: use with ion-exchange separation for
      spectrophotometric determination of zinc in plant digests.
AB  - A novel strategy for utilization of solid reagents in flow analysis is proposed.
      Establishment of diffuse and reproducible geometry enables the solid particles to
      be maintained in constant floating, reflux, and circulating motion inside a mini
      chamber. This is efficiently accomplished with pulsed flows, a characteristic of
      multi-pumping flow systems. Drawbacks inherent in solid-phase packed columns, for
      example backpressure, preferential pathways, swelling, etc., and some limitations
      inherent in immobilized reagents are minimised. Spectrophotometric determination
      of zinc in plants was selected as an application of the technique. Dowex 1-X8
      anionic resin was kept freely inside a mini-chamber. Zinc chloro-complexes were
      adsorbed on the moving particles and derivatization with zincon was performed
      after elution. Analytical figures of merit and the potential and limitations of
      the approach are discussed.

PMID- 16408215
TI  - The identification of human tumour antigens: Current status and future
      developments.
AB  - The biggest challenge facing us today in cancer control and prevention is the
      identification of novel biomarkers for detection and improved therapeutic
      interventions to reduce mortality and morbidity rates. Biomarkers are important
      indicators to inform us of the physiological state of the cell at a specific
      time. It is now clear that malignant transformation occurs by changes in cellular
      DNA and protein expression with subsequent clonal proliferation of the altered
      cells. The affected genes and their expressed protein products or biomarkers are
      those involved in the normal growth and maintenance of the cancerous cells. These
      biomarkers could prove pivotal for the identification of early cancer and people
      at risk of developing cancer. Altered proteins or changes in gene expression in
      malignant cells may lead to the expression of tumour antigens recognised by host
      immune system. In this review we discuss current research into the molecular
      technologies making possible the global genomic-wide analysis of changes in DNA
      (genotyping), RNA expression (transcriptomics) and protein expression
      (proteomics) that have accelerated the rate of new biomarker/tumour antigen
      discovery. To gain a comprehensive understanding of the physiology and
      pathophysiology of cancer an approach that harmoniously integrates the various
      'omic' platforms are key to unraveling the complexity 'needle-in-a-haystack'
      quality of biomarker/tumour antigen discovery.

PMID- 16408217
TI  - Multiple-scattering extended X-ray absorption fine structure analysis of
      nanostructured iron(III) oxide in the pore system of mesoporous carbon CMK-1.
AB  - This work is devoted to the EXAFS analysis of nanostructured iron(III) oxide
      synthesized inside the pore system of mesoporous carbon CMK-1. A detailed study
      of the recording, preparation and evaluation of data recorded in fluorescence
      mode at the iron K-edge with and without multiple scattering is shown. The
      results obtained show that the local structure of Fe3+ inside nanostructured
      iron(III) oxide is different to that of the bulk material. Due to the small
      particle size, data analysis is much more difficult and data preparation more
      complex. Incorporating multiple scattering paths in the Fourier transforms and
      back-transforms during data evaluation gives structural insights that cannot be
      obtained using other spectroscopic methods, and this technique was used to draw
      conclusions about the first four coordination spheres of the nanostructured
      iron(III) oxide.

PMID- 16408218
TI  - [Mycosis fungoides and B-cell chronic lymphocytic leukemia: an extremely rare
      coincidence].
AB  - The simultaneous appearance of mycosis fungoides (MF) and B-cell chronic
      lymphocytic leukemia (B-CLL) in the same patient is extremely rare. Only seven
      cases have been described in literature. A 72-year-old patient was diagnosed with
      coincident MF, stage Ib, and B-CLL, Binet stage A. Hypotheses on simultaneous
      occurrence of B- and T-cell malignancies as well as a new therapeutic option are
      discussed.

PMID- 16408219
TI  - [Dronabinol for supportive therapy in patients with malignant melanoma and liver
      metastases].
AB  - BACKGROUND: Loss of appetite and nausea can reduce the quality of life of
      patients with malignant melanoma and liver metastases. Often established
      antiemetic drugs fail to bring relief. Tetrahydrocannabinol (THC, Marinol), which
      is the active agent of Indian hemp, has been used successfully in this situation
      for other malignant tumors. PATIENTS AND METHODS: We treated 7 patients with
      hematogenous metastatic melanoma and liver metastases suffering from extensive
      loss of appetite and nausea supportively with dronabinol (Marinol. All of these
      patients had previously received standard antiemetic therapy without adequate
      relief. Dronabinol is a synthetic Delta-tetrahydrocannabinol. The drug was
      administered in capsule form. We evaluated the palliative effects of dronabinol
      with a special patient evaluation form, which was filled out at the beginning of
      the therapy and again after 4 weeks. RESULTS: The majority of patients described
      a significant increase in appetite and decrease in nausea. These effects remained
      for some weeks, but then decreased as metastases progressed and the general
      condition worsened. All of the patients experienced slight to moderate dizziness,
      but it was not sufficiently troubling to cause interruption or termination of
      therapy. CONCLUSION: Loss of appetite and nausea due to liver metastases of
      malignant melanoma can be treated in individual cases supportively with
      Dronabinol.

PMID- 16408220
TI  - Follicular dendritic cell tumor of the mediastinum: expression of fractalkine and
      SDF-1alpha as mast cell chemoattractants.
AB  - Follicular dendritic cell tumor (FDCT) is a rare tumor mainly located in
      laterocervical lymph nodes. We report one case of mediastinal FDCT associated
      with a history of bullous skin disease and clinically obvious immunosuppression.
      This tumor was characterized by heavy mast cell infiltration. Mast cells were in
      close relationship with tumor cells as demonstrated by ultrastructural
      examination and their presence are probably related with the strong expression of
      mast cell chemoattractants as fraktalkine and stromal cell-derived factor-1alpha
      by tumor cells. The long follow-up period of more than 17 years allowed to us
      assess the relatively indolent evolution of this tumor characterized by three
      slowly growing local recurrences without metastasis.

PMID- 16408221
TI  - Chromogranin A in gastric neuroendocrine tumours: an immunohistochemical and
      biochemical study with region-specific antibodies.
AB  - The aim of the present study was to investigate ECLomas and enterochromaffin-like
      (ECL) cell hyperplasia in gastric human mucosa regarding the immunohistochemical
      expression of chromogranin A (CgA) epitopes and to measure the same CgA epitopes
      in plasma samples. Eight gastric biopsies from ECLomas, seven of type I and one
      of type III, and biopsies from one patient showing only ECL cell hyperplasia were
      included in the study. Our results revealed a varying expression of region
      specific CgA epitopes in the ECLomas regarding both the frequency of
      immunoreactive cells and intensity of immunoreactivity. CgA284-301
      (pancreastatin) was not revealed in any neoplasm, whereas CgA361-372 (catestatin)
      was expressed in all ECLomas. However, the number of immunoreactive cells to
      vesicular monoamino transporter 2 (VMAT 2) or the commercial monoclonal CgA
      (CgA250-284) antibodies were generally higher. The plasma concentrations of the
      region-specific CgA radioimmunoassays differed considerably, with highest
      concentrations of CgA1-17 and CgA116-130 epitopes and the lowest with the CgA17
      37, CgA63-76, CgA238-247 and CgA441-424 epitopes. No relationship was found
      between tissue expression and plasma concentration of CgA epitopes. In
      conclusion, this study shows that VMAT 2 and the commercial CgA antibodies seem
      more useful for histopathological diagnosis of ECLomas than the antibodies to the
      other CgA regions.

PMID- 16408222
TI  - Y-chromosomes and the extent of patrilineal ancestry in Irish surnames.
AB  - Ireland has one of the oldest systems of patrilineal hereditary surnames in the
      world. Using the paternal co-inheritance of Y-chromosome DNA and Irish surnames,
      we examined the extent to which modern surname groups share a common male-line
      ancestor and the general applicability of Y-chromosomes in uncovering surname
      origins and histories. DNA samples were collected from 1,125 men, bearing 43
      different surnames, and each was genotyped for 17 Y-chromosome short tandem
      repeat (STR) loci. A highly significant proportion of the observed Y-chromosome
      diversity was found between surnames demonstrating their demarcation of real and
      recent patrilineal kinship. On average, a man has a 30-fold increased chance of
      sharing a 17 STR Y-chromosome haplotype with another man of the same surname but
      the extent of congruence between the surname and haplotype varies widely between
      surnames and we attributed this to differences in the number of early founders.
      Some surnames such as O'Sullivan and Ryan have a single major ancestor, whereas
      others like Murphy and Kelly have numerous founders probably explaining their
      high frequency today. Notwithstanding differences in their early origins, all
      surnames have been extensively affected by later male introgession. None examined
      showed more than about half of current bearers still descended from one original
      founder indicating dynamic and continuously evolving kinship groupings. Precisely
      because of this otherwise cryptic complexity there is a substantial role for the
      Y-chromosome and a molecular genealogical approach to complement and expand
      existing sources.

PMID- 16408223
TI  - Does the mitochondrial genome play a role in the etiology of Alzheimer's disease?
AB  - We report here the analyses of complete mtDNA coding region sequences from more
      than 270 Alzheimer's disease (AD) patients and normal controls to determine if
      inherited mtDNA mutations contribute to the etiology of AD. The AD patients and
      normal individuals were carefully screened and drawn from two populations of
      European descent in an effort to avoid spurious effects due to local population
      anomalies. Overall, there were no significant haplogroup associations in the
      combined AD and normal control sequence sets. Reduced median network analysis
      revealed that the AD mtDNA sequences contained a higher number of substitutions
      in tRNA genes, and that there was an elevated frequency of replacement
      substitutions in the complex I genes of the control sequences. Analysis of the
      replacement substitutions indicated that those arising in the AD mtDNAs were no
      more deleterious, on average, than those in the control mtDNAs. The only evidence
      for the synergistic action of mutations was the presence of both a rare non
      conservative replacement substitution and a tRNA mutation in 2 AD mtDNAs, from a
      total of 145, whereas such a combination of mutations was not observed in the
      control sequences. Overall, the results reported here indicate that pathogenic
      inherited mtDNA mutations do not constitute a major etiological factor in
      sporadic AD. At most, a small proportion of AD patients carry a pathogenic mtDNA
      mutation and a small proportion of cognitively normal aged individuals carry a
      mtDNA mutation that reduces the risk of AD.

PMID- 16408224
TI  - MUTYH and the mismatch repair system: partners in crime?
AB  - Biallelic germline mutations of MUTYH-a gene encoding a base excision repair
      protein-are associated with an increased susceptibility of colorectal cancer.
      Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear,
      although there is some evidence suggesting a slight increase of risk. As the
      MUTYH protein interacts with the mismatch repair (MMR) system, we hypothesised
      that the combination of a monoallelic MUTYH mutation with an MMR gene mutation
      increases cancer risk. We therefore investigated the prevalence of monoallelic
      MUTYH mutations in carriers of a germline MMR mutation: 40 carriers of a
      truncating mutation (group I) and 36 of a missense mutation (group II). These
      patients had been diagnosed with either colorectal or endometrial cancer. We
      compared their MUTYH mutation frequencies with those observed in a group of 134
      Dutch colorectal and endometrial cancer patients without an MMR gene mutation
      (0.7%) and those reported for Caucasian controls (1.5%). In group I one
      monoallelic MUTYH mutation was found (2.5%). In group II five monoallelic
      germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation
      carriers (20%). Of all patients with an MMR gene mutation, only those with a
      missense mutation showed a significantly higher frequency of (monoallelic) MUTYH
      mutations than the Dutch cancer patients without MMR gene mutations (P = 0.002)
      and the published controls (P = 0.001). These results warrant further study to
      test the hypothesis of mutations in MMR genes (in particular MSH6) and MUTYH
      acting together to increase cancer risk.

PMID- 16408225
TI  - Lack of effect of growth hormone replacement therapy on CYP1A2 and xanthine
      oxidase activities in growth hormone-deficient children.
AB  - BACKGROUND AND OBJECTIVES: The recombinant human growth hormone (rhGH) is being
      increasingly used for a number of metabolic alterations. GH is the main regulator
      of several hepatic drug metabolizing enzymes in rodents. In addition, GH could
      play a major role in defining the interface between pharmacogenetics and
      development. However, little is known about the effect of GH on the activity of
      hepatic enzymes in children. The aim of this study was to determine the effect of
      rhGH replacement therapy for 4 weeks on CYP1A2 and xanthine oxidase (XO)
      activities in children. METHODS: We used caffeine as a probe drug to assess the
      enzyme activities at two points in time: before starting GH treatment (day 0) and
      after 4 weeks on rhGH therapy (day A). A total of 31 GH-deficient children (age
      range: 4.1-13.1 years, mean age: 9.88+/-2.89 years) participated. Urinary
      concentrations of caffeine and metabolites were determined by high-performance
      liquid chromatography (HPLC) to calculate the metabolite ratios: (AFMU+1X+1U)/17U
      for CYP1A2 and 1U/(1X+1U) for XO. RESULTS: Four weeks of GH substitution did not
      importantly alter the markers of the enzyme activities measured in this study.
      Median values and 95% confidence intervals (CI) at baseline were 5.17 (3.87-5.59)
      for the CYP1A2 ratio and 0.62 (0.56-0.65) for the XO ratio. These values, after
      treatment, were 4.57 (3.90-5.97) for the CYP1A2 marker and 0.62 (0.59-0.67) for
      the XO ratio. Data comparison between periods showed lack of statistically
      significant differences (P>0.05). The relative changes measured by the ratios of
      medians and 90% CI were 1.14 (0.90-1.31) and 0.99 (0.94-1.06) for CYP1A2 and XO,
      respectively. CONCLUSIONS: The absence of significant changes in the markers of
      enzyme activities CYP1A2 and XO suggests that rhGH replacement therapy of GH
      deficient children for 4 weeks could not noticeably modify the efficacy or
      toxicity of substrates of these metabolic enzymes.

PMID- 16408226
TI  - Increasing use of medicines in elderly persons: a five-year follow-up of the
      Kuopio 75+Study.
AB  - OBJECTIVE: The aim of this study was to describe the changes in medicine use,
      polypharmacy and excessive polypharmacy between 1998 and 2003 among a cohort of
      elderly Finns. METHODS: For this prospective follow-up study, a random sample of
      700 participants aged >or=75 years was drawn from the City of Kuopio, Finland. Of
      them, 601 participated in the study at baseline in 1998. The changes in medicine
      use among the survivors (n=339), who were re-examined in 2003, were recorded and
      are described here. Statistical significance of changes in medicine use was
      evaluated by Student's paired-samples and independent-samples t-test and Fisher's
      exact test. RESULTS: From 1998 to 2003, the mean number of medicines in use per
      individual increased from 6.3 to 7.5 (p<0.001). The prevalence of polypharmacy
      (>5 medicines in use) increased from 54% to 67% and excessive polypharmacy
      (>or=10 medicines in use) from 19% to 28%. The increase was due to increased use
      of regularly taken medicines, whereas the use of medicines taken as needed
      decreased during the follow-up in both sexes. At the time of follow-up survey,
      persons in institutional care used significantly more medicines (10.9) than
      community-dwelling elderly persons (7.0) (p<0.001). Central nervous system
      medicines and cardiovascular medicines were the most commonly used medicines in
      both years. CONCLUSION: The number of medicines and the prevalence of
      polypharmacy and excessive polypharmacy increases with advancing age. In order to
      avoid possible harmful effects and to optimize medication it is necessary to
      assess the medication regimen at regular intervals.

PMID- 16408227
TI  - Comments on Glintborg et al.'s drug-drug interactions study (EJCP 2005; 61: 675
      681).

PMID- 16408228
TI  - Endogenous production of endo-beta-1,4-glucanase by decapod crustaceans.
AB  - The potential ability to produce cellulase enzymes endogenously was examined in
      decapods crustaceans including the herbivorous gecarcinid land crabs Gecarcoidea
      natalis and Discoplax hirtipes, the amphibious freshwater crab Austrothelphusa
      transversa, the terrestrial hermit crab, Coenobita variabilis the parastacid
      crayfish Euastacus, and the crayfish Cherax destructor. The midgut gland of both
      G. natalis and D. hirtipes contained substantial total cellulase activities and
      activities of the cellulase enzymes endo-beta-1,4-glucanase and beta-glucosidase.
      With the exception of total cellulase and beta-glucosidase from D. hirtipes, the
      enzyme activities within the midgut gland were higher than those within the
      digestive juice. Hence, the enzyme activities appear to reside predominantly
      within midgut gland, providing indirect evidence for endogenous synthesis of
      cellulase enzymes by this tissue. A 900 bp cDNA fragment encoding a portion of
      the endo-beta-1,4-glucanase amino acid sequence was amplified by RT-PCR using RNA
      isolated from the midgut gland of C. destructor, Euastacus, A. transversa and C.
      variabilis. This provided direct evidence for the endogenous production of endo
      beta-1,4-glucanase. The 900 bp fragment was also amplified from genomic DNA
      isolated from the skeletal muscle of G. natalis and D. hirtipes, clearly
      indicating that the gene encoding endo-beta-1,4-glucanase is also present in
      these two species. As this group of evolutionary diverse crustacean species
      possesses and expresses the endo-beta-1,4-glucanase gene it is likely that
      decapod crustaceans generally produce cellulases endogenously and are able to
      digest cellulose.

PMID- 16408229
TI  - How might you compare mitochondria from different tissues and different species?
AB  - Mitochondria were isolated from the liver, kidney and mixed hindlimb skeletal
      muscle of three vertebrate species; the laboratory rat Rattus norvegicus, the
      bearded dragon lizard Pogona vitticeps, and the cane toad Bufo marinus. These
      vertebrate species are approximately the same body mass and have similar body
      temperatures. The content of cytochromes B, C, C1, and A were measured in these
      isolated mitochondria by oxidised-reduced difference spectra. Adenine nucleotide
      translocase (ANT) was measured by titration of mitochondrial respiration with
      carboxyactractyloside and the protein and phospholipid content of isolated
      mitochondria were also measured. Fatty acid composition of mitochondrial
      phospholipids was measured. Mitochondrial respiration was measured at 37 degrees
      C under states III and IV conditions as well as during oligomycin inhibition.
      Species differed in the ratios of different mitochondrial cytochromes. Muscle
      mitochondria differed from kidney and liver mitochondria by having a higher ANT
      content relative to cytochrome content. Respiration rates were compared relative
      to a number of denominators and found to be most variable when expressed relative
      to mitochondrial protein content and least variable when expressed relative to
      mitochondrial cytochrome A and ANT content. The turnover of cytochromes was
      calculated and found to vary between 1 and 94 electrons s(-1). The molecular
      activity of mitochondrial cytochromes was found to be significantly positively
      correlated with the relative polyunsaturation of mitochondrial membrane lipids.

PMID- 16408230
TI  - Response of female cuttlefish Sepia officinalis (Cephalopoda) to mirrors and
      conspecifics: evidence for signaling in female cuttlefish.
AB  - Cuttlefish have a large repertoire of body patterns that are used for camouflage
      and interspecific signaling. Intraspecific signaling by male cuttlefish has been
      well documented but studies on signaling by females are lacking. We found that
      females displayed a newly described body pattern termed Splotch toward their
      mirror image and female conspecifics, but not to males, prey or inanimate
      objects. Female cuttlefish may use the Splotch body pattern as an intraspecific
      signal, possibly to reduce agonistic interactions. The ability of females to
      produce a consistent body pattern in response to conspecifics and mirrors
      suggests that they can recognize same-sex conspecifics using visual cues, despite
      the lack of sexual dimorphism visible to human observers.

PMID- 16408231
TI  - [Depth of anaesthesia during intubation: comparison between propofol and
      thiopentone].
AB  - In order to study the depth of anaesthesia during endotracheal intubation, 30
      patients received either thiopentone or propofol for anaesthesia induction. The
      BIS value as a parameter for the depth of anaesthesia and the rate pressure
      product (RPP) were acquired online. Patients who received thiopentone for
      anaesthesia induction showed significantly higher BIS values at the moment of
      intubation and reached BIS values >60 significantly more frequently than patients
      receiving propofol. The RPP in the propofol group lay significantly below that of
      the thiopentone patients. For all patients there was an mean increase in BIS
      values of 8 index points and an increase in the RPP. Therefore, BIS values around
      50 should be achieved before intubation in order to avoid the critical BIS value
      for awareness of >60 despite the increase caused by the intubation procedure.
      Within 24 h of intubation all patients were interviewed for possible signs of
      awareness. None of the patients was able to remember the intubation or reported
      other experiences that indicated an unconscious awareness. Nevertheless, the
      progress of BIS values in a standardized intubation as performed in the normal
      clinical routine, shows that the use of thiopentone for initiating anaesthesia
      results in a very flat level of anaesthesia during intubation. The risk for
      patients to experience awareness should therefore, not be underestimated.
      Therefore, when using thiopentone it is recommended to also use a rapid acting
      muscle relaxant or to select a high ED95 to compensate for the flat level of
      anaesthesia. Alternatively, repetetive boluses of the hypnotic shortly before
      intubation should be considered or to revert to propofol. The dosage and
      pharmacokinetics of the analgesic should also be taken into consideration because
      an insufficient analgesia leads to a faster flattening of the depth of
      anaesthesia.

PMID- 16408232
TI  - Daily physical activity and its relation to aerobic fitness in children aged 8-11
      years.
AB  - A positive relationship between daily physical activity and aerobic fitness
      exists in adults. Studies in children have given conflicting results, possibly
      because of differences in methods used to assess daily physical activity and
      fitness. No study regarding daily physical activity and fitness in children has
      been published, where fitness has been assessed by direct measurement of maximum
      oxygen uptake and related to daily physical activity intensities by
      accelerometers. We examined 248 children (140 boys and 108 girls), aged 7.9-11.1
      years. Maximum workload and maximal oxygen uptake (VO2PEAK) by indirect
      calorimetry were measured during a maximum bicycle ergometer exercise test.
      Exercise capacity was adjusted for body mass and (body mass)2/3. Daily physical
      activity was evaluated by accelerometers, worn around the waist for 4 days. Mean
      accelerometer counts and time spent in vigorous physical activity were
      calculated. VO2PEAK was correlated with mean accelerometer counts (r=0.23 for
      boys and r=0.23 for girls, both P<0.05), but somewhat better with time spent in
      vigorous activity (r=0.32 for boys, r=0.30 for girls, both P<0.05). All results
      remained virtually the same regardless of the method used to adjust for
      differences in body size.

PMID- 16408233
TI  - Influence of the menstrual cycle on proenkephalin peptide F responses to maximal
      cycle exercise.
AB  - Proenkephalin peptide F [107-140] is an enkephalin-containing peptide found
      predominantly within the adrenal medulla and is co-packaged with epinephrine
      within adrenal medullary chromaffin granules. Peptide F has been shown to have
      the classic opioid analgesia effects along with immune cell interactions. This is
      only the second peptide F study in women, and in it we compare the responses of
      peptide F to a maximal cycle exercise test and recovery values over the
      follicular and luteal phases of the menstrual cycle. Eight untrained (directly
      documented in this study) women who were eumenorrheic performed a progressive
      maximal exercise test to volitional exhaustion on a cycle ergometer, once during
      the follicular phase, and once during the luteal phases of the menstrual cycle.
      Blood was obtained pre-exercise, immediately post-exercise and at 0, 15, and 30
      min into recovery. Typical exercise changes in response to the cycle tests were
      observed with blood lactate increases that remained elevated 30 min into
      recovery. No significant exercise-induced elevations were observed for peptide F
      concentrations with exercise nor were any differences observed between the two
      menstrual phases. Thus, the effects of the menstrual cycle on peptide F
      concentrations appear to be minimal under the conditions of this investigation.
      With high concentrations of peptide F observed at rest (approx. 0.2-0.3 pmol ml(
      1)) pre-exercise arousal mechanisms may have obviated any exercise-induced
      response. In addition, inhibition via elevated epinephrine may have inhibited any
      post-exercise increases and finally adrenal medullary capacity for circulatory
      concentrations of peptide F may have been reached in such untrained women. Pre
      exercise arousal mechanisms potentially related to analgesia may also be involved
      to prepare untrained women for the stress of maximal exercise.

PMID- 16408234
TI  - The effects of short-term sprint training on MCT expression in moderately
      endurance-trained runners.
AB  - The purpose of this study was to assess the effects of short-term sprint training
      on transient changes in monocarboxylate lactate transporter 1 (MCT1) and MCT4
      protein and mRNA content. Seven moderately endurance-trained runners (mean +/-
      SE; age 27.7+/-2.9 years, body mass 81.1+/-5.9 kg, .VO(2max) 58.1+/-2.0 ml kg(-1)
      min(-1)) completed a .VO(2max) and a supramaximal running test to exhaustion
      (RTE) before and after a 6-week period of sprint training. The sprint training
      was progressive and consisted of 18 sessions of near maximal short duration (5-15
      s) sprints to compliment the athlete's endurance training. Prior to the training
      period there was a significant (P<0.05) increase in MCT1, but not MCT4 protein, 2
      h after the RTE. This occurred without any change in corresponding mRNA levels.
      After the training period, there was a significant increase in MCT1 protein but
      no significant change in the MCT4 isoform. Both MCT1 and MCT4 mRNA was
      significantly lower at rest and 2 h post-RTE after the completion of the training
      period. After the training period, there was a significant increase in the time
      to exhaustion and distance covered during the RTE. This study demonstrates that
      sprint training of this length and type results in an upregulation of MCT1
      protein, but not MCT4 content. Additionally, this study shows conflicting
      adaptations in MCT1 and MCT4 protein and mRNA levels following training, which
      may indicate post-transcriptional regulation of MCT expression in human muscle.

PMID- 16408235
TI  - Combined anterior and posterior instrumentation in severe and rigid idiopathic
      scoliosis.
AB  - A prospective clinical and radiographic evaluation of 33 consecutive patients
      with severe and rigid idiopathic scoliosis (average Cobb angle 93 degrees,
      flexibility on bending films 23%) were treated with combined anterior and
      posterior instrumentation with a minimum follow-up of 2 years. All patients
      underwent anterior release and VDS-Zielke Instrumentation of the primary curve.
      In highly rigid scoliosis, this was preceded by a posterior release. Finally,
      posterior correction and fusion with a multiple hook and pedicle screw construct
      was performed. Thirty patients were operated in one stage, three patients in two
      stages. Preoperative curves ranged from 80 to 122 degrees Cobb angle. Frontal
      plane correction of the primary curve averaged 67% with an average loss of
      correction of 2 degrees . The apical vertebral rotation of the primary curve was
      corrected by 49%. In all but three patients, sagittal alignment was restored.
      There were no neurological complications, deep wound infections or
      pseudarthrosis. Combined anterior and posterior instrumentation is safe and
      enables an effective three-dimensional curve correction in severe and rigid
      idiopathic scoliosis.

PMID- 16408236
TI  - Analysis of hard thoracic herniated discs: review of 18 cases operated by
      thoracoscopy.
AB  - The authors retrospectively reviewed a series of 18 hard thoracic herniated discs
      (HTHD) operated by thoracoscopy. Isolated cases of HTHD have been reported in the
      literature, but no series describing these lesions has been published. Seventy
      two percent of the herniated discs were situated between T8 and T12. Fifty-six
      percent of the patients had radiographic sequelae of Scheuermann's disease.
      Postoperatively, 83% had neurological improvement. In seven cases (39%), a plane
      separating the herniated disc and the dura mater was found surgically. In 11
      patients, no separating plane was found during surgery. The lesion was intradural
      in three patients (17%) and adherent to the dura mater in eight (44%). Among
      these 11 patients, surgery was complicated by a dural tear in the first seven
      that led to a high risk of cerebrospinal fluid fistula: four of these seven
      patients had required surgical revision. In the last four, the zone of adhesion
      of the HTHD to the dura mater was preserved, successfully preventing dural tear.

PMID- 16408237
TI  - Spine fractures caused by horse riding.
AB  - STUDY DESIGN: Retrospective study and review of literature. OBJECTIVES: Study of
      demographic data concerning spinal fractures caused by horse riding,
      classification of fractures according to the AO and Load Sharing classifications,
      evaluation of mid-term radiological results and long-term functional results.
      METHODS: A review of medical reports and radiological examinations of patients
      presented to our hospital with horse riding-related spine fractures over a 13
      year period; long-term functional follow-up is performed using the Roland Morris
      Disability Questionnaire (RMDQ-24). RESULTS: Thirty-six spine fractures were
      found in 32 patients. Male to female ratio is 1:7. Average age is 33.7 years (8
      58 years). The majority of the fractures (78%) are seen at the thoracolumbar
      junction Th11-L2. All but two patients have AO type A fractures. The average Load
      Sharing Classification score is 4.9 (range 3-9). Neurological examinations show
      ASIA/Frankel E status for all patients. Surgical treatment is performed on ten
      patients. Mean follow-up for radiological data is 15 months (range 3-63).
      Functional follow-up times range from 1 to 13 years with an average follow-up of
      7.3 years. Mean RMDQ-24 score for all patients is 5.5 (range: 0-19), with
      significantly different scores for the non-operative and surgical group: 4.6 vs
      8.1. Twenty-two percent of the patients have permanent occupational disabilities
      and there is a significant correlation between occupational disability and RMDQ
      24 scores. CONCLUSIONS: Not only are short-term effects of spine fractures caused
      by horse riding substantial but these injuries can also lead to long-term
      disabilities.

PMID- 16408238
TI  - Ectopic meningioma: a case report with a literature review.
AB  - Ectopic (extradural) meningiomas that do not originate from either the optic
      fascicle or the intracranial meninges are exceedingly rare. A patient with an
      ectopic meningioma in the external auditory canal and mastoid was treated in our
      unit. The world literature of the last 20 years was reviewed.

PMID- 16408239
TI  - Effects of ropivacaine on transient-evoked otoacoustic emissions: a rabbit model.
AB  - The aim of this study was to investigate the effect of ropivacaine, a newer amide
      local anesthetic, on the ears of rabbits by using transient-evoked otoacoustic
      emissions (TEOAEs). Thirty rabbits were studied in a random block design of six
      groups of five animals each. There received intra-tympanically instilled single
      doses of 0.5 mg/kg, 1.0 mg/kg of ropivacaine, 0.5 ml of isotonic saline (control
      for intratympanic application), or intravenously administered single doses of 1.0
      mg/kg, 2.0 mg/kg of ropivacaine and 1.0 ml of isotonic saline (control for
      intravenous application). Cochlear function was serially monitored using TEOAEs
      before administration and on the 1st and 15th days after administrations of
      ropivacaine or isotonic saline. The responses of TEOAEs were analyzed in terms of
      mean stimulus, stability, wave reproducibility and emission amplitudes at 1.0-4.0
      kHz. We found no significant changes in the TEOAE responses of the baseline
      measurements in each group before administration and the responses at each
      interval in the same group after administration throughout the experiment (P >
      0.05). Also, no significant difference was found between the group receiving
      ropivacaine administered intravenously or intratympanicly and the control group
      at each interval (P > 0.05). The data from the present study showed that
      ropivacaine, whether administered intravenously or intratympanically and even at
      a low or high dose, has no effects on the responses of TEOAEs in the early
      period. These findings encourage the use of ropivacaine as a safe agent without
      ototoxic effects in peripheral nerve blocks, epidural and intravenous regional
      anesthesia or even tinnitus therapy in the future.

PMID- 16408240
TI  - Efficacy and comorbidity of oral appliances in the treatment of obstructive sleep
      apnea-hypopnea: a systematic review and preliminary results of a randomized
      trial.
AB  - The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep-related
      breathing disorder characterized by repetitive obstructions of the upper airway
      during sleep. The modification of pharyngeal patency by oral appliance therapy
      has been suggested as an alternative to various treatment modalities for OSAHS.
      To determine the evidence base with respect to the efficacy and comorbidity of
      the oral appliance therapy in OSAHS, a systematic review of the available
      literature was conducted. In addition, the preliminary results of a randomized
      parallel trial are reported on the effectiveness and specific indication of,
      respectively, the oral appliance and continuous positive airways pressure therapy
      in OSAHS.

PMID- 16408241
TI  - Adaptive evolution and recombination of Rickettsia antigens.
AB  - The genus Rickettsia consists of intracellular bacteria that cause a variety of
      arthropod vectored human diseases. I have examined the evolutionary processes
      that are generating variation in antigens that are potential vaccine candidates.
      The surface proteins rOmpA and rOmpB are subject to intense positive natural
      selection, causing rapid diversification of their amino acid sequences between
      species. The positively selected amino acids were mapped and cluster together in
      regions that may indicate the location of functionally important regions such as
      epitopes. In contrast to the rOmp antigens, there is no evidence of positive
      selection on the intracytoplasmic antigen PS120 despite low selective constraints
      on this gene. All three genes showed evidence of recombination between species,
      and certain sequences are clear chimeras of two parental sequences. However,
      recombination has been sufficiently infrequent that the phylogenies of the three
      genes are similar, although not identical.

PMID- 16408242
TI  - The mariner transposons belonging to the irritans subfamily were maintained in
      chordate genomes by vertical transmission.
AB  - Mariner-like elements (MLEs) belong to the Tc1-mariner superfamily of DNA
      transposons, which is very widespread in animal genomes. We report here the first
      complete description of a MLE, Xtmar1, within the genome of a poikilotherm
      vertebrate, the amphibian Xenopus tropicalis. A close relative, XlMLE, is also
      characterized within the genome of a sibling species, Xenopus laevis. The
      phylogenetic analysis of the relationships between MLE transposases reveals that
      Xtmar1 is closely related to Hsmar2 and Bytmar1 and that together they form a
      second distinct lineage of the irritans subfamily. All members of this lineage
      are also characterized by the 36- to 43-bp size of their imperfectly conserved
      inverted terminal repeats and by the -8-bp motif located at their outer
      extremity. Since XlMLE, Xlmar1, and Hsmar2 are present in species located at both
      extremities of the vertebrate evolutionary tree, we looked for MLE relatives
      belonging to the same subfamily in the available sequencing projects using the
      amino acid consensus sequence of the Hsmar2 transposase as an in silico probe. We
      found that irritans MLEs are present in chordate genomes including most
      craniates. This therefore suggests that these elements have been present within
      chordate genomes for 750 Myr and that the main way they have been maintained in
      these species has been via vertical transmission. The very small number of
      stochastic losses observed in the data available suggests that their inactivation
      during evolution has been very slow.

PMID- 16408243
TI  - Rate variation as a function of gene origin in plastid-derived genes of peridinin
      containing dinoflagellates.
AB  - Peridinin-pigmented dinoflagellates contain secondary plastids that seem to have
      undergone more nearly complete plastid genome reduction than other eukaryotes.
      Many typically plastid-encoded genes appear to have been transferred to the
      nucleus, with a few remaining genes found on minicircles. To understand better
      the evolution of the dinoflagellate plastid, four categories of plastid
      associated genes in dinoflagellates were defined based on their history of
      transfer and evaluated for rate of sequence evolution, including minicircle genes
      (presumably plastid-encoded), genes probably transferred from the plastid to the
      nucleus (plastid-transferred), and genes that were likely acquired directly from
      the nucleus of the previous plastid host (nuclear-transferred). The fourth
      category, lateral-transferred genes, are plastid-associated genes that do not
      appear to have a cyanobacterial origin. The evolutionary rates of these gene
      categories were compared using relative rate tests and likelihood ratio tests.
      For comparison with other secondary plastid-containing organisms, rates were
      calculated for the homologous sequences from the haptophyte Emiliania huxleyi.
      The evolutionary rate of minicircle and plastid-transferred genes in the
      dinoflagellate was strikingly higher than that of nuclear-transferred and lateral
      transferred genes and, also, substantially higher than that of all plastid
      associated genes in the haptophyte. Plastid-transferred genes in the
      dinoflagellate had an accelerated rate of evolution that was variable but, in
      most cases, not as extreme as the minicircle genes. Furthermore, the nuclear
      transferred and lateral-transferred genes showed rates of evolution that are
      similar to those of other taxa. Thus, nucleus-to-nucleus transferred genes have a
      more typical rate of sequence evolution, while those whose history was wholly or
      partially within the dinoflagellate plastid genome have a markedly accelerated
      rate of evolution.

PMID- 16408244
TI  - LTR retrotransposon-gene associations in Drosophila melanogaster.
AB  - Thirty-three percent (228/682) of all long terminal repeat (LTR) retrotransposon
      sequences (LRSs) present in the sequenced Drosophila melanogaster genome were
      found to be located in or within 1000 bp of a gene. Recently inserted LTR
      retrotransposons are significantly more likely to be located in or within genes
      than are older, fragmented LTR retrotransposon sequences, indicating that most
      LRS-gene associations are selected against over evolutionary time. LRSs
      associated with conserved genes (homologenes) are especially prone to negative
      selection. In contrast, fragmented LRSs that have persisted in the genome over
      long spans of evolutionary time are preferentially associated with genes involved
      in signal transduction and other newly evolved functions.

PMID- 16408245
TI  - Interactions between yeasts and grapevines: filamentous growth,
      endopolygalacturonase and phytopathogenicity of colonizing yeasts.
AB  - It has been clearly established that phytopathogenic fungi, bacteria, and viruses
      exert biotic stresses on plants. Much less is known, however, about the
      interactions between enological species of yeast and their host plants. In a
      previous study, we described how Saccharomyces cerevisiae, the most common
      enological yeast, can act as a grapevine (Vitis vinifera L.) pathogen, causing
      growth retardation or plant death. In the present in vitro study on 11 strains of
      yeast belonging to different genera, which often occur on the surfaces of
      vineyard grapes and V. vinifera, a link was found to exist between strain
      phytopathogenecity and pseudohyphal growth habits and/or endopolygalacturonase
      activity. The results obtained here are consistent with earlier findings showing
      that the phytopathogenicity of yeast strains depends on the filamentous growth
      process, and show that endopolygalacturonase alone is not responsible for the
      invasion of plants tissues. The mechanisms observed here may be of significant
      ecological importance and may help to explain the long periods of yeast survival
      found to occur in vineyards.

PMID- 16408246
TI  - Smoke treatment triggers the release of a novel DNA damaging factor by
      lymphocytes.
AB  - Organic fuel smoke is a hazardous agent, which pushes the cells
      towards"prooxidant state'', leading to 4,46,400 strand breaks/cell/day as against
      47,000 strand breaks/cell/day produced by constitutive oxygen radicals. This
      prooxidants scenario switches on a plethora of intercellular events. Here we
      report a novel DNA damaging factor released by lymphocytes, upon treatment with
      smoke condensate. Human lymphocytes, when exposed to cow dung cake smoke
      condensate, were found to release a low molecular weight factor into the media at
      20 min of exposure. The conditioned media, displayed a propensity of inducing DNA
      damage in fresh, normal lymphocytes, which were not exposed to any damaging
      agent. The above DNA damaging effect of the conditioned media was not due to any
      residual presence of Polycyclic Aromatic Hydrocarbons, which were present in the
      smoke. The release of this factor was in correlation with the DNA damaging event,
      taking place in the cells. This secondary DNA damaging factor had a molecular
      weight less than 5 kd. The factor had the cell death inducing propensity when
      allowed to act on lymphocytes.

PMID- 16408247
TI  - A single copy of carbonic anhydrase 2 restores wild-type circadian period to
      carbonic anhydrase II-deficient mice.
AB  - Carbonic anhydrase II (CA-II)-deficient mice have long circadian periods compared
      to their siblings with normal CA-II levels. The CA-II-deficient mice differ
      genetically from their siblings at proximal chromosome three, where the mutated
      carbonic anhydrase 2 gene sits on a small insert of DNA from the DBA/2J strain.
      The rest of the genome is that of the C57BL/6J strain. The goal of this study was
      to test the hypothesis that the null mutation in carbonic anhydrase 2 and the
      long circadian period phenotype were linked. In order to separate the effect of
      the null mutation in carbonic anhydrase 2 from the effect of DBA/2J alleles of
      other genes on the insert, two new lines of mice were studied. The first line,
      Kar, was developed from a CA-II-deficient mouse that had a fortuitous
      recombination restoring functional CA-II without affecting the rest of the DBA/2J
      insert. The second line was generated by breeding DBA/2J mice and C57BL/6J mice
      until they had the genomic composition of CA-II-deficient mice without the null
      mutation. Both lines of mice had circadian periods not different from C57BL/6J
      mice and shorter than CA-II-deficient mice. The phenotype of the new lines showed
      that the long circadian period characteristic of the CA-II-deficient mice arises
      when functional CA-II is absent, not when DBA/2J alleles are present on proximal
      chromosome three.

PMID- 16408248
TI  - QTL analysis of behavioral and morphological differentiation between wild and
      laboratory zebrafish (Danio rerio).
AB  - The zebrafish is an important model organism for neuro-anatomy and developmental
      genetics. It also offers opportunities for investigating the functional and
      evolutionary genetics of behaviour but these have yet to be exploited. The
      ecology of anti-predator behaviour has been widely studied in fish and has been
      shown to vary among populations and between wild and domesticated (laboratory)
      fish. Here, we utilise the strong behavioural differences present between a wild
      derived strain of fish from Bangladesh and the laboratory strain AB. In total,
      184 F2 fish were generated and tested for shoaling tendency and willingness to
      approach an unfamiliar object ('boldness'). Our results indicate the existence of
      QTL for boldness on chromosomes 9 and 16 and suggest another genomic region that
      influences anti-predator behaviour on chromosome 21. QTL for growth rate, weight
      and fat content, all of which are elevated in laboratory fish, were detected on
      chromosome 23. These initial results confirm the potential for QTL mapping of
      behavioural traits in zebrafish and also for dissecting the consequences of
      selection during domestication.

PMID- 16408249
TI  - Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing
      pheromone-induced aggression.
AB  - The rodent preputial gland secretes aggression-promoting pheromones and expresses
      melanocortin-5 receptor (MC5R), but the functional relationship is poorly
      understood. We investigated whether MC5R deficiency in male mice alters
      stimulatory melanocortin influences on preputial growth and pheromone-induced
      aggression. In wild-type (MC5R(+/+)) pairs, repeated NDP-MSH injection decreased
      attack latency and increased aggression in initial attackers. Similar NDP-MSH
      treatment in MC5R-deficient (MC5R(-/-)) pairs failed to alter attack latency or
      aggression frequency, but aggression increased in vehicle-injected opponents. NDP
      MSH treatment promoted preputial hypertrophy, and in MC5R(+/+) mice paired
      against non-aggressive stimulus opponents it decreased attack latency and
      increased aggression. MC5R(-/-) mice were insensitive to behavioral and
      physiological effects of NDP-MSH, and preputialectomized mice were insensitive to
      behavioral effects of NDP-MSH. The results suggest that MC5R inactivation reduced
      a pheromonal signal for aggression that acts on donors, rather than their
      opponents.

PMID- 16408250
TI  - Individual differences in puberty onset in girls: Bayesian estimation of
      heritabilities and genetic correlations.
AB  - : We report heritabilities for individual differences in female pubertal
      development at the age of 12. Tanner data on breast and pubic hair development in
      girls and data on menarche were obtained from a total of 184 pairs of monozygotic
      and dizygotic twins. Genetic correlations were estimated to determine to what
      extent the same genes are involved in different aspects of physical development
      in puberty. A Bayesian estimation approach was taken, using Markov-chain Monte
      Carlo simulation to estimate model parameters. All three phenotypes were to a
      significant extent heritable and showed high genetic correlations, suggesting
      that a common set of genes is involved in the timing of puberty in general.
      However, gonadarche (menarche and breast development) and adrenarche (pubic hair)
      are affected by different environmental factors, which does not support the three
      phenotypes to be regarded as indicators of a unitary physiological factor.

PMID- 16408251
TI  - Limitations of system integration in providing employment services for persons
      with mental illness.
AB  - This study assessed the influence of service systems integration on employment
      outcomes for persons with mental illness. A survey was sent to all 125 key
      program staff that worked for community mental health treatment agencies or
      vocational rehabilitation agencies. The survey found that referral and employment
      rates were low; but that these rates were related to characteristics of the
      interagency systems integration. Community mental health staff referred 448
      individuals for employment services. Staff from vocational rehabilitation
      agencies accepted only 26% of these referrals and found work for just 11%; 7%
      were employed six months later. Also, 39% of respondents reported that the
      linkage agreement between their agencies was never established. This study
      suggests the need for more effective strategies for integrating mental health
      treatment and vocational rehabilitation systems.

PMID- 16408252
TI  - Method of delivery and neonatal mortality among very low birth weight infants in
      the United States.
AB  - OBJECTIVE: To examine the association between method of delivery (primary
      cesarean section vs. vaginal) and neonatal mortality risk (as well as causes of
      death) among very low-birth weight first-born infants in the United States. More
      specifically, to examine this association separately for breech/malpresenting and
      vertex-presenting infants, while adjusting for selected maternal characteristics,
      and pregnancy, labor and delivery complications. METHODS: The study population
      was derived from the 1995-1998 birth cohort linked birth/infant death data sets.
      Binary and multinomial logit regression analyses were performed to assess the
      relationship in four very low-birth weight categories. RESULTS: Among
      breech/malpresenting neonates, compared to those delivered vaginally, infants
      delivered by a primary cesarean section had significantly lower adjusted relative
      risks of death for all very low-birth weight categories and the decrease in
      relative risk tended to be larger with each increasing birth weight category.
      However, for vertex-presenting neonates, results are mixed, suggesting decreased
      relative mortality risks associated with primary cesarean section, which were
      significant for 500-749 g, not significant for 750-999 g, and barely significant
      for 1,000-1,249 g. In contrast, for vertex-presenting neonates weighing 1,250
      1,499 g, there was a significantly increased adjusted relative risk associated
      with primary cesarean section. Differences in cause-specific neonatal mortality
      by method of delivery and presentation status were also discussed. CONCLUSIONS:
      Primary cesarean section appears to be associated with decreased neonatal
      mortality risks in each very low-birth weight category for breech/malpresenting
      infants, but results are mixed for vertex-presenting infants. Causal inferences
      should be avoided because this was an observational study by design.

PMID- 16408254
TI  - Evaluating statistical significance in two-stage genomewide association studies.
AB  - Genomewide association studies are being conducted to unravel the genetic
      etiology of complex human diseases. Because of cost constraints, these studies
      typically employ a two-stage design, under which a large panel of markers is
      examined in a subsample of subjects, and the most-promising markers are then
      examined in all subjects. This report describes a simple and efficient method to
      evaluate statistical significance for such genome studies. The proposed method,
      which properly accounts for the correlated nature of polymorphism data, provides
      accurate control of the overall false-positive rate and is substantially more
      powerful than the standard Bonferroni correction, especially when the markers are
      in strong linkage disequilibrium.

PMID- 16408255
TI  - A permutation test for inference in logistic regression with small- and moderate
      sized data sets.

PMID- 16408258
TI  - Effects of water deprivation for 72 hours on the pharmacokinetics of DA-7867, a
      new oxazolidinone, in rats.
AB  - The pharmacokinetic parameters of DA-7867 were compared after intravenous and
      oral administration at a dose of 10 mg/kg in control rats and in rats with water
      deprivation for 72 h (rat model of dehydration). After intravenous administration
      in the rat model of dehydration, the Cl(nr) (0.654 versus 0.992 ml/min/kg) and
      Cl(r) (0.0273 versus 0.0784 ml/min/kg) values were significantly slower than in
      the controls. The slower Cl(nr) could be due mainly to a significantly smaller
      total amount of unchanged DA-7867 recovered from the gastrointestinal tract at 24
      h (GI(24 h): 5.16% versus 9.21% of intravenous dose) due to impaired liver
      function in the rat model of dehydration. The slower Cl(r) could be due mainly to
      a significantly smaller 24 h urinary excretion of unchanged drug (Ae(0-24 h):
      4.41% versus 7.75% of intravenous dose) due to urine flow rate-dependent Cl(r) of
      DA-7867 in the rat model of dehydration. Hence, the Cl was significantly slower
      in the rat model of dehydration (0.677 versus 1.07 ml/min/kg). After intravenous
      administration in the rat model of dehydration, the V(ss) of DA-7867 was
      significantly smaller than in the controls (396 versus 506 ml/kg) due mainly to
      significantly smaller free (unbound to plasma proteins) fractions of DA-7867 in
      plasma (6.90% versus 29.2%) in the rat model of dehydration. After oral
      administration in the rat model of dehydration, the AUC was significantly greater
      than that in controls (10800 versus 7060 microg min/ml) due mainly to a
      significantly smaller Ae(0-24 h) than in controls (3.50% and 6.17% of oral dose).

PMID- 16408259
TI  - Cystometric and in vitro muscle studies of cystoplastic appendiceal segments in
      the rat.
AB  - AIMS: The functional integration of the smooth muscle of enterocystoplasties into
      the detrusor muscle was investigated in an awake-rat cystometry model and in
      vitro. METHODS: The upper fourth of the bladder was removed, and a detubularized
      appendiceal segment (7 x 7 mm), with preserved vasculature, was incorporated into
      the bladder. After 1 or 3 months, a catheter was fixed to the top of the
      bladders. After a 3-day recovery, cystometries were performed. In separate
      experiments, agonist and nerve-induced responses were evaluated on isolated
      bladder strips. RESULTS: Cystometries revealed reduced basal pressure and
      micturition pressure in enterocystoplasty (ECP) bladders. Bladder capacity and
      micturition volume were increased. Threshold pressure (pressure immediately
      before micturition) was significantly lower at 1 month, but not at 3 months.
      Bladder compliance was significantly higher in the operated at 1 month but not at
      3 months. Threshold tension did not differ between control and corresponding
      operated groups. Residual urine was significantly higher in the operated groups.
      ECP strips showed increased maximal contractions to nerve stimulation, to levels
      similar to those of detrusor strips. Maximal responses to carbachol increased to
      levels between those of intestine and detrusor. The inhibitory effect of
      scopolamine on nerve induced contractions increased to levels similar to those
      for detrusor. Purinergic activation had no effect on intestinal or ECP strips,
      but contracted detrusor muscle. CONCLUSIONS: The smooth muscle of the bowel
      segment in rat ECP bladders underwent a partial change in the response to nerve
      stimulation from that of intestine towards that of detrusor. The cystometry
      experiments suggested a partial functional integration of the ECP segment into
      the detrusor.

PMID- 16408260
TI  - Immunodetection of the serotonin transporter protein is a more valid marker for
      serotonergic fibers than serotonin.
AB  - Tracking serotonergic pathways in the brain through immunodetection of serotonin
      has widely been used for the anatomical characterization of the serotonergic
      system. Immunostaining for serotonin is also frequently applied for the
      visualization of individual serotonin containing fibers and quantification of
      serotonin positive fibers has been widely used to detect changes in the
      serotonergic innervation. However, particularly in conditions with enhanced
      serotonin metabolism the detection level of serotonin may lead to an
      underestimation of the true number of serotonergic fibers. The serotonin
      transporter (SERT) protein, on the other hand, is less liable to metabolism and
      for that reason we hypothetized that SERT immunostaining is a more stable marker
      of serotonergic fibers. Rats were pretreated with monoamine oxidase (MAO)
      inhibitor and compared with placebo treated rats. Brains were double
      immunostained for serotonin and SERT protein and colocalization was quantified in
      several brain areas by confocal microscopy. In comparison with untreated rats,
      MAO inhibitor treated rats had a significantly higher number (almost 200%
      increase) of serotonin immunopositive fibers whereas no difference was observed
      in the number of the SERT positive fibers. Colocalization between serotonin and
      SERT positive fibers was close to 100% in MAO inhibitor treated animals but only
      30% in untreated rats. We conclude that the rapid metabolism of serotonin leads
      to an underestimation of immunodetected serotonergic fibers and that in many
      instances, SERT immunostaining may be a better indicator of serotonergic fibers.

PMID- 16408261
TI  - The effects of adulthood nicotine treatment on D2-mediated behavior and
      neurotrophins of rats neonatally treated with quinpirole.
AB  - This study was designed to analyze the effects of nicotine on yawning behavior
      and neurotrophin content in the hippocampus and frontal cortex of D2-receptor
      primed female adult Sprague-Dawley rats. Animals were neonatally treated with
      quinpirole, a dopamine (DA) D2/D3 agonist, from postnatal day 1-21 (P1-21) and
      raised to P60 and administered nicotine tartarate (0.3 mg/kg free base) or saline
      twice daily for 14 days. One day after nicotine treatment had ceased, the number
      of yawns was recorded for 1 h in response to an acute injection of quinpirole
      (i.p., 100 microg/kg). Yawning is a D2-receptor mediated event. D2-primed rats
      demonstrated a significant increase in yawning in response to acute quinpirole
      compared with that of controls, but nicotine did not alleviate this effect.
      Neonatal quinpirole treatment produced a significant decrease of nerve growth
      factor (NGF) and brain-derived neurotrophic factor (BDNF) in the hippocampus that
      was alleviated by adulthood nicotine treatment. Interestingly, nicotine treatment
      to controls produced a significant increase of NGF in the frontal cortex, but a
      significant decrease of both NGF and BDNF in the hippocampus and BDNF in the
      frontal cortex. The decreases shown in NGF and BDNF is contrary to past findings
      that have shown nicotine to produce significant increases of hippocampal NGF and
      BDNF, but these past studies utilized male rats or mice or were performed in
      vitro. This study shows that nicotine has complex interactions with NGF and BDNF
      in D2-primed and control animals, and emphasizes the importance of gender
      differences when analyzing nicotine's effects on neurotrophins.

PMID- 16408262
TI  - Single breath-hold whole-heart MRA using variable-density spirals at 3T.
AB  - Multislice breath-held coronary imaging techniques conventionally lack the
      coverage of free-breathing 3D acquisitions but use a considerably shorter
      acquisition window during the cardiac cycle. This produces images with
      significantly less motion artifact but a lower signal-to-noise ratio (SNR). By
      using the extra SNR available at 3 T and undersampling k-space without
      introducing significant aliasing artifacts, we were able to acquire high
      resolution fat-suppressed images of the whole heart in 17 heartbeats (a single
      breath-hold). The basic pulse sequence consists of a spectral-spatial excitation
      followed by a variable-density spiral readout. This is combined with real-time
      localization and a real-time prospective shim correction. Images are
      reconstructed with the use of gridding, and advanced techniques are used to
      reduce aliasing artifacts.

PMID- 16408263
TI  - Noninvasive detection of cuprizone induced axonal damage and demyelination in the
      mouse corpus callosum.
AB  - Previously, we tested the prediction that axonal damage results in decreased
      axial diffusivity (lambda(parallel)) while demyelination leads to increased
      radial diffusivity (lambda(perpendicular)). Cuprizone treatment of C57BL/6 mice
      was a highly reproducible model of CNS white matter demyelination and
      remyelination affecting the corpus callosum (CC). In the present study, six
      C57BL/6 male mice were fed 0.2% cuprizone for 12 weeks followed by 12 weeks of
      recovery on normal chow. The control mice were fed normal chow and imaged in
      parallel. Biweekly in vivo DTI examinations showed transient decrease of
      lambda(parallel) in CC at 2-6 weeks of cuprizone treatment. Immunostaining for
      nonphosphorylated neurofilaments demonstrated corresponding axonal damage at 4
      weeks of treatment. Significant demyelination was evident from loss of Luxol fast
      blue staining at 6-12 weeks of cuprizone ingestion and was paralleled by
      increased lambda(perpendicular) values, followed by partial normalization during
      the remyelination phase. The sensitivity of lambda(perpendicular) to detect
      demyelination may be modulated in the presence of axonal damage during the early
      stage of demyelination at 4 weeks of cuprizone treatment. Our results suggest
      that lambda(parallel) and lambda(perpendicular) may be useful in vivo surrogate
      markers of axonal and myelin damage in mouse CNS white matter.

PMID- 16408264
TI  - Parallel imaging of hyperpolarized helium-3 with simultaneous slice excitation.
AB  - Hyperpolarized (HP) gas imaging of the lungs is an ideal potential application
      for parallel imaging. This is due to the fact that there is limited scan time
      (breath hold of 20 s) and limited non-renewable polarization. Reduced phase
      encode parallel imaging is demanding on hardware in that it requires multiple
      receivers. In this work, simultaneous parallel acquisition of hyperpolarized (HP)
      3He images from multiple slices was demonstrated in phantoms and in vivo using a
      simultaneous slice excitation method, at a field strength of 1.5 T. The pulse
      sequence allows simultaneous acquisition of n slices per RF excitation, thus
      reducing the number of RF pulses needed to fully cover a given volume with multi
      slicing. Unlike conventional parallel imaging, this method does not require prior
      reference scan information, which would consume some of the finite longitudinal
      polarization in lung ventilation studies with HP gas.

PMID- 16408265
TI  - Correction of through-plane deformation artifacts in stimulated echo acquisition
      mode cardiac imaging.
AB  - Attempts to use a stimulated echo acquisition mode (STEAM) in cardiac imaging are
      impeded by imaging artifacts that result in signal attenuation and nulling of the
      cardiac tissue. In this work, we present a method to reduce this artifact by
      acquiring two sets of stimulated echo images with two different demodulations.
      The resulting two images are combined to recover the signal loss and weighted to
      compensate for possible deformation-dependent intensity variation. Numerical
      simulations were used to validate the theory. Also, the proposed correction
      method was applied to in vivo imaging of normal volunteers (n = 6) and animal
      models with induced infarction (n = 3). The results show the ability of the
      method to recover the lost myocardial signal and generate artifact-free black
      blood cardiac images.

PMID- 16408266
TI  - Characterizing radial undersampling artifacts for cardiac applications.
AB  - The undersampled radial acquisition has been widely employed for accelerated (by
      a factor R = N(r)/N(p)) cardiac imaging, but the resulting reduction in image
      quality has not been well characterized. This investigation presents a method of
      measuring these artifacts through synthetic undersampling of high SNR images (SNR
      > or = 30). After validating the method in phantoms, the method was applied to a
      study of short-axis, long-axis, and coronary MRI imaging in healthy subjects. For
      60 projections (60 N(p)), the total artifact is approximately 10% for short and
      long-axis imaging (R = 2.1) and approximately 15% for coronary MRI (R = 3.7). For
      60 N(p), the SD of artifact in the region of the heart is 2% for short- and long
      axis imaging (R = 2.1) and 3.5% for coronary MRI (R = 3.7). The artifact content
      is less in the region of the heart than in the periphery. The artifact is very
      reproducible among subjects for standard views. A study of coronary MRI at
      progressively fewer projections (at constant scan time) showed that right
      coronary MRI images were acceptable if total artifact was <6.5% of image content
      (N(p) > 120, R = 2.1).

PMID- 16408267
TI  - Dual-echo spiral in/in acquisition method for reducing magnetic susceptibility
      artifacts in blood-oxygen-level-dependent functional magnetic resonance imaging.
AB  - MRI signal dropout in gradient recalled echo acquisitions limits the capability
      of blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) to
      study activation tasks that involve the orbitofrontal, temporal, and basal areas
      of the brain where significant macroscopic magnetic susceptibility differences
      exist. Among the various approaches aimed to address this issue, the acquisition
      method based on spiral in/out trajectories is one of the most time-efficient and
      effective techniques. In this study, we extended further the spiral in/out
      approach into 3D acquisition and compared the effectiveness of the different
      spiral in/out trajectory combinations in reducing signal dropout. The activation
      results from whole brain fMRI studies using complex finger tapping and breath
      holding tasks demonstrate that the acquisition method based on dual-echo spiral
      in/in (DSPIN) trajectories is the most favorable. The DSPIN acquisition method
      has the following advantages: (1) It reduces most effectively signal dropout in
      the brain where magnetic susceptibility inhomogeneity is problematic and
      significantly improves the sensitivity to detect functional activations in those
      regions. (2) It significantly improves SNR in the whole brain by dual echo
      averaging without compromising functional contrast. (3) There is no reduction in
      time-efficiency and spatial resolution.

PMID- 16408268
TI  - Expression analysis and modulation by HIV-Tat of the tyrosine phosphatase HD-PTP.
AB  - The human immunodeficiency virus type 1 Tat transactivates viral proteins and
      also affects the expression of eukaryotic genes. Since Tat is angiogenic, we
      assumed that the isolation of differentially expressed genes in Tat-treated
      endothelial cells would yield insights into the molecular mechanisms of the
      angiogenic process. By RNA fingerprinting, we found that Tat upregulates the
      tyrosine phosphatase HD-PTP mRNA in a human endothelial cell line. At the moment,
      little is known about HD-PTP. We here show that HD-PTP is highly conserved
      through evolution from yeast to man, and is ubiquitously distributed in adult and
      fetal tissues. HD-PTP is expressed in human cell lines derived from different
      tumors, but the mRNA levels do not appear to correlate with the malignant
      phenotype of the cells. HD-PTP mRNA was also detected in cell lines derived from
      tumors that develop in BKV/Tat-transgenic mice. Interestingly, a relation exists
      between the amounts of secreted Tat and the levels of HD-PTP mRNA. HD-PTP encodes
      a 185-kDa protein which is expressed in human endothelial from the umbilical cord
      and in human Kaposi-spindle cells. Tat-induction of HD-PTP mRNA parallels only
      with a slight increase of the protein, which occurs after 24 and 48 h of
      incubation in the presence of Tat. These results suggest that HD-PTP amounts
      might be regulated both at the transcriptional and post-transcriptional levels.

PMID- 16408269
TI  - Identification of amino-terminal region of adiponectin as a physiologically
      functional domain.
AB  - Adiponectin is an abundant adipose-specific protein, which acts as an anti
      diabetic, anti-atherogenic, and anti-inflammatory adipokine. Although recent
      advances in the field of adiponectin have been made by the identification of
      adiponectin receptors and by the understanding about relationship between its
      multimerization and functions, detailed molecular background remains unclear. Our
      established anti-human adiponectin antibodies, ANOC 9103 and ANOC 9104, blocked
      some adiponectin functions such as the growth inhibition of B-lymphocytes on
      stromal cells and the inhibition of acetylated LDL uptake in macrophages,
      suggesting that they may recognize important functional regions of adiponectin.
      As a result of epitope mapping based on the ability to bind to the deleted
      adiponectin mutants, we identified that these antibodies recognize amino-terminal
      region of adiponectin before the beginning of the collagen-like domain. Notably,
      a peptide fragment (DQETTTQGPGVLLPLPKGACTGWMA) corresponding to amino acid
      residues 17-41 of human adiponectin could bind to restricted types of cells and
      block adiponectin-induced cyclooxygenase-2 gene expression and prostaglandin E2
      production in MS-5 stromal cells. Moreover, the deletion of its amino-terminal
      region reduced the abilities to inhibit not only collagen-induced platelet
      aggregation but also diet-induced hepatic steatosis. These data indicate that
      amino-terminal region of adiponectin is a physiologically functional domain and
      that a novel receptor, which recognizes amino-terminal region of adiponectin, may
      exist on some types of cells. Further investigations will contribute to the
      understanding of molecular mechanisms about adiponectin functions as well as to
      the designing of novel strategies for the treatment of patients with insulin
      resistance, vascular dysfunction, and chronic inflammation.

PMID- 16408270
TI  - Diastolic coronary artery compression in a cardiac transplant recipient:
      treatment with a stent.

PMID- 16408271
TI  - Controlled aliasing in volumetric parallel imaging (2D CAIPIRINHA).
AB  - The CAIPIRINHA (Controlled Aliasing In Parallel Imaging Results IN Higher
      Acceleration) concept in parallel imaging has recently been introduced, which
      modifies the appearance of aliasing artifacts during data acquisition in order to
      improve the subsequent parallel imaging reconstruction procedure. This concept
      has been successfully applied to simultaneous multi-slice imaging (MS
      CAIPIRINHA). In this work, we demonstrate that the concept of CAIPIRINHA can also
      be transferred to 3D imaging, where data reduction can be performed in two
      spatial dimensions simultaneously. In MS CAIPIRINHA, aliasing is controlled by
      providing individual slices with different phase cycles by means of alternating
      multi-band radio frequency (RF) pulses. In contrast to MS CAIPIRINHA, 2D
      CAIPIRINHA does not require special RF pulses. Instead, aliasing in 2D parallel
      imaging can be controlled by modifying the phase encoding sampling strategy. This
      is done by shifting sampling positions from their normal positions in the under
      sampled 2D phase encoding scheme. Using this modified sampling strategy, coil
      sensitivity variations can be exploited more efficiently in multiple dimensions,
      resulting in a more robust parallel imaging reconstruction.

PMID- 16408272
TI  - Generalized self-navigated motion detection technique: Preliminary investigation
      in abdominal imaging.
AB  - Patient motion remains a primary obstacle to diagnostic image quality, especially
      in the abdomen, despite the existence of various motion artifact reduction
      techniques. This work presents a self-navigated motion detection method that can
      be generalized for most pulse sequences and k-space trajectories. Motion
      information is extracted directly from raw MR data, requiring no additional
      gradient or RF pulses, no physiologic monitoring equipment, and minimal--if any-
      impact on scan time. Initial feasibility results with a two-dimensional gradient
      echo sequence are shown in phantom studies and in vivo volunteer abdominal
      studies, demonstrating the sensitivity of the method to both respiratory motion
      and cardiovascular pulsatility. Prospectively gated images were acquired using
      the self-navigated data to synchronize image acquisition with motion. These
      preliminary results suggest that the self-navigated method is a promising
      technique for reducing motion artifacts in clinical abdominal and cardiac
      applications.

PMID- 16408273
TI  - Noninvasive measurement of myocardial tissue volume change during systolic
      contraction and diastolic relaxation in the canine left ventricle.
AB  - In coronary circulation the flow in epicardial arteries and veins is observed to
      be pulsatile and out of phase with each other. Theoretical considerations predict
      that this phenomenon extends to all levels of the vascular tree and leads to a
      cyclic fluctuation of regional tissue volume. Intramyocardial tissue volume
      change between end-systole and end-diastole was measured noninvasively with MRI
      in 10 closed-chest beagles. The displacement encoding with stimulated-echo
      technique was used to obtain pixel-by-pixel tissue displacement field between end
      diastole and end-systole and vice versa in the midlevel left ventricle, from
      which the 3D strain matrix and volume changes were calculated. The volume change
      was between 0.8+/-0.5% (mean+/-STD) in the epicardial layer and 1.5+/-0.6% in the
      subendocardial layer of the left ventricle. Tissue volume fluctuation reflects
      the amount of arterial inflow in a heartbeat under the assumption that regional
      arterial inflow and venous outflow have little time overlap. The corresponding
      perfusion level was estimated to be from (1.0+/-0.6) ml/min/g in the epicardial
      layer to (1.7+/-0.6) ml/min/g in the subendocardial layer, in good agreement with
      microsphere measurements in the same dog model. The result supports the notion of
      high arterial resistance at the microvascular level from intramyocardial pressure
      during systole.

PMID- 16408274
TI  - Intracellular acidification delays hormonal G2/M transition and inhibits G2/M
      transition triggered by thiophosphorylated MAPK in Xenopus oocytes.
AB  - Xenopus oocyte maturation is analogous to G2/M transition and characterized by
      germinal vesicle breakdown (GVBD), spindle formation, activation of MPF and Mos
      Xp42(Mpk1) pathways. It is accompanied prior to GVBD by a transient increase in
      intracellular pH. We determined that a well known acidifying compound, NH(4)Cl,
      delayed progesterone-induced GVBD in a dose-dependent manner. GVBD(50) was
      delayed up to 2.3-fold by 10 mM NH(4)Cl. Cyclin B2 phosphorylation, Cdk1 Tyr15
      dephosphorylation as well as p39(Mos) accumulation, Xp42(Mpk1) and p90(Rsk)
      phosphorylation induced by progesterone were also delayed by incubation of oocyte
      in NH(4)Cl. The delay induced by NH(4)Cl was prevented by injection of MOPS
      buffer pH 7.7. In contrast to acidifying medium, alkalyzing treatment such as
      Tris buffer pH 9 injections, accelerated GVBD, MPF and Xp42(Mpk1) activation,
      indicating that pHi changes control early steps of G2/M dynamics. When injected
      in an immature recipient oocyte, egg cytoplasm triggers GVBD through MPF auto
      amplification, independently of protein synthesis. In these conditions, GVBD and
      Xp42(Mpk1) activation were delayed by high concentration of NH(4)Cl, which never
      prevented or delayed MPF activation. Strickingly, NH(4)Cl strongly inhibited
      thiophosphorylated active MAPK-induced GVBD and MPF activation. Nevertheless,
      Tris pH 9 did not have any effects on egg cytoplasm- or active MAPK-induced GVBD.
      Taken together, our results suggest that dynamic of early events driving
      Xp42(Mpk1) and MPF activation induced by progesterone may be negatively or
      positively regulated by pH(i) changes. However Xp42(Mpk1) pathway was inhibited
      by acidification alone. Finally, MPF auto-amplification loop was not sensitive to
      pH(i) changes.

PMID- 16408275
TI  - Bovine microvascular endothelial cells immortalized with human telomerase.
AB  - Primary cultures of bovine microvascular endothelial cells (BME) isolated from
      the adrenal cortex, are commonly used to study vascular endothelium, but have a
      limited life span. To circumvent these limitations, we have immortalized BME
      cells with either simian virus 40 (SV40) or with a retrovirus containing the
      coding region of human telomerase reverse transcriptase (hTERT), and have
      investigated whether the clonal populations obtained, maintain differentiated
      properties characteristic of microvascular endothelium. Immortalized cells were
      characterized for maintenance of typical endothelial morphology, marker
      expression, and functional characteristics including uptake of Acetylated low
      density lipoprotein (Ac-LDL), capillary-like tube formation in three-dimensional
      collagen gels, as well as metalloproteinase (MMP) and plasminogen activator (PA)
      mediated extracellular proteolysis. Whilst immortalization of BME cells with SV40
      was associated with loss of endothelial-specific properties, hTERT-BME exhibited
      an endothelial phenotype similar to that of wild-type endothelial cells.
      Specifically, they showed a typical cobblestone morphology, were contact
      inhibited, expressed endothelial cell-specific markers (e.g., CD31, vWF) and both
      fibroblast growth factor receptor 1 (FGFR-1) and vascular endothelial growth
      factor receptor-2 (VEGFR-2). In addition, they expressed receptors for LDL.
      Importantly, when grown on collagen gels, hTERT-BME cells underwent MMP-dependent
      tube-like structure formation in response to VEGFR-2 activation. In a collagen
      gel sandwich assay, hTERT-BME formed tubular structures in the absence of
      exogenously added angiogenic cytokines. Sustained tube formation was induced by
      VEGF-A alone or in combination with FGF-2. From 17 sub-clones that displayed a
      non-transformed phenotype, a high proliferative capacity and tubulogenic
      properties in three-dimensional collagen gels, we isolated two distinct
      subpopulations that display a highly specific response to VEGF-A or to FGF-2. We
      have generated hTERT-BME cells that maintain endothelial-specific properties and
      function and have isolated clones that respond differentially to VEGF-A or FGF-2.
      These immortalized cell lines will facilitate the study of endothelial cell
      biology.

PMID- 16408276
TI  - Tissue fibrosis and carcinogenesis: divergent or successive pathways dictate
      multiple molecular therapeutic targets for oligo decoy therapies.
AB  - The extracellular matrix (ECM) is composed of several families of macromolecular
      components: fibrous proteins such as collagens, type I collagen (COL1), type III
      collagen (COL3), fibronectin, elastin, and glycoconjugates such as proteoglycans
      and matrix glycoproteins. Their receptors on the cell membrane, most of which in
      the case of the ECM belong to the integrins, which are heterodimeric proteins
      composed of alpha and beta chains. COL1 is the major fibrous collagen of bone,
      tendon, and skin; while COL3 is the more pliable collagen of organs like liver.
      Focus will not only be given to the regulation of synthesis of several fibrogenic
      parameters but also modulation of their degradation during growth factor-induced
      tissue fibrosis and cancer development. Evidence will be provided that certain
      tissues, which undergo fibrosis, also become cancerous. Why does there exist a
      divergency between tissues, which undergo frank fibrosis as an endpoint, and
      those tissues that undergo fibrosis and subsequently are susceptible to
      carcinogenicity; resulting from the etiological factor(s) causing the initial
      injury? For example, why does a polyvinyl alcohol (PVA) sponge implant become
      encapsulated and filled with fibrous tissue then fibrosis tissue growth stops?
      Why does the subcutaneous injection of a fibrogenic growth factor cause a benign
      growth and incisional wounding results in fibrosis and ultimately scarring? There
      are many examples of tissues, which undergo fibrosis as a prerequisite to
      carcinogenesis. Is there a cause-effect relationship? If you block tissue
      fibrosis in these precancerous tissues, would you block cancer formation? What
      are the molecular targets for blocking fibrosis and ultimately carcinogenesis?
      How can oligo decoys may be used to attenuate carcinogenesis and which oligo
      decoys specifically attenuate fibrogenesis as a prelude to carcinogenesis? What
      are other molecular targets for oligo decoy therapy in carcinogenesis?

PMID- 16408278
TI  - Force meets chemistry: analysis of mechanochemical conversion in focal adhesions
      using fluorescence recovery after photobleaching.
AB  - Mechanotransduction--the process by which mechanical forces are converted into
      changes of intracellular biochemistry--is critical for normal cell and tissue
      function. Integrins facilitate mechanochemical conversion by transferring
      physical forces from the extracellular matrix, across the cell surface, and to
      cytoskeletal-associated proteins within focal adhesions. It is likely that force
      alters biochemistry at these sites by altering molecular binding affinities of a
      subset of focal adhesion proteins, but this has been difficult to quantify within
      living cells. Here, we describe how the fluorescence recovery after
      photobleaching (FRAP) technique can be adapted and used in conjunction with
      mathematical models to directly measure force-dependent alterations in molecular
      binding and unbinding rate constants of individual focal adhesion proteins in
      situ. We review these recent findings, and discuss the strengths and limitations
      of this approach for analysis of mechanochemical signaling in focal adhesions and
      other cellular structures. The ability to quantify molecular binding rate
      constants in the physical context of the living cytoplasm should provide new
      insight into the molecular basis of cellular mechanotransduction. It also may
      facilitate future efforts to bridge biological experimentation and mathematical
      modeling in our quest for a systems biology level description of cell regulation.

PMID- 16408277
TI  - IGF-1 increases laminin, cyclin D1, and p21Cip1 expression in glomerular
      mesangial cells: an investigation of the intracellular signaling pathway and cell
      cycle progression.
AB  - Insulin-like growth factor (IGF)-1 is accumulated in the diabetic kidney and is
      considered to be involved in the development of glomerular sclerosis. Here, we
      investigate IGF-1 regulation of laminin, an extracellular matrix (ECM) component,
      and cyclin D1 and p21Cip1, cell-cycle progression factor, expressions in
      glomerular mesangial cells. We show that IGF-1 increases the level of laminin
      gamma1 and beta1 subunits approximately 1.5- and 2.5-fold, respectively, in a
      time-dependent manner. IGF-1 also stimulates protein kinase Akt/PKB
      phosphorylation at Thr 308, which correlates with its activity, up to 24 h. The
      Akt activation is coupled with Ser 9 phosphorylation of its downstream target,
      glycogen synthase kinase-3beta (GSK-3beta), which inhibits its kinase activity.
      Laminin beta1 is reduced significantly (P < 0.03) by inhibitors of Akt and
      p38MAPK whereas laminin gamma1 is not affected. Surprisingly, IGF-1 activates the
      expression of both cyclin D1 and cell-cycle arrest factor, p21Cip1 parallely.
      Pharmacological inhibition of calcineurin by cyclosporin A blocks IGF-1-induced
      cyclin D1 and p21Cip1expression significantly (P < 0.05). IGF-1 enhances cellular
      metabolic activity and viability of rat mesangial cells; however, they are
      arrested at the G1 phase of cell cycle as revealed by the FACS analysis. These
      results indicate that IGF-1 mediates mesangial cell-cycle progression,
      hypertrophy, and ECM protein synthesis. The Akt/GSK-3beta, p38MAPK, and
      calcineurin pathways may play an important role in IGF-1 signaling, cell-cycle
      regulation, and matrix gene expression in mesangial cells leading to the
      development of diabetic glomerulopathy.

PMID- 16408279
TI  - Nucleus pulposus cells express HIF-1 alpha under normoxic culture conditions: a
      metabolic adaptation to the intervertebral disc microenvironment.
AB  - Nucleus pulposus (NP) cells of the intervertebral disc reside in an environment
      that has a limited vascular supply and generate energy through anaerobic
      glycolysis. The goal of the present study was to examine the expression and
      regulation of HIF-1alpha, a transcription factor that regulates oxidative
      metabolism in nucleus pulposus cells. Nucleus pulposus cells were isolated from
      rat, human, and sheep disc and maintained at either 21% or 2% oxygen for various
      time periods. Cells were also treated with desferrioxamine (Dfx), a compound that
      mimics the effects of hypoxia (Hx). Expression and function of HIF-1alpha were
      assessed by immunofluorescence microscopy, Western blot analysis, gel shift
      assays, and luciferase reporter assays. In normoxia (Nx), rat, sheep, and human
      nucleus pulposus cells consistently expressed the HIF-1alpha subunit. Unlike
      other skeletal cells, when maintained under low oxygen tension, the nucleus
      pulposus cells exhibited a minimal induction in HIF-1alpha protein levels.
      Electromobility shift assays confirmed the functional binding of normoxic HIF
      1alpha protein to its putative DNA binding motif. A dual luciferase reporter
      assay showed increased HIF-1alpha transcriptional activity under hypoxia compared
      to normoxic level, although this induction was small when compared to HeLa and
      other cell types. These results indicate that normoxic stabilization of HIF
      1alpha is a metabolic adaptation of nucleus pulposus cells to a unique oxygen
      limited microenvironment. The study confirmed that HIF-1alpha can be used as a
      phenotypic marker of nucleus pulposus cells.

PMID- 16408280
TI  - The significance of telomeric aggregates in the interphase nuclei of tumor cells.
AB  - Telomeres are TTAGGG repetitive motifs found at the ends of vertebrate
      chromosomes. In humans, telomeres are protected by shelterin, a complex of six
      proteins (de Lange [2005] Genes Dev. 19: 2100-2110). Since (Muller [1938]
      Collecting Net. 13: 181-198; McClintock [1941] Genetics 26: 234-282), their
      function in maintaining chromosome stability has been intensively studied. This
      interest, especially in cancer biology, stems from the fact that telomere
      dysfunction is linked to genomic instability and tumorigenesis (Gisselsson et al.
      [2001] Proc. Natl. Acad. Sci. USA 98: 12683-12688; Deng et al. [2003] Genes
      Chromosomes Cancer 37: 92-97; DePinho and Polyak [2004] Nat. Genetics 36: 932
      934; Meeker et al. [2004] Clin. Cancer Res. 10: 3317-3326). In the present
      overview, we will discuss the role of telomeres in genome stability, recent
      findings on three-dimensional (3D) changes of telomeres in tumor interphase
      nuclei, and outline future avenues of research.

PMID- 16408281
TI  - Minimum-norm reconstruction for sensitivity-encoded magnetic resonance
      spectroscopic imaging.
AB  - In this work we propose minimum-norm reconstruction as a means to enhance the
      spatial response behavior in parallel spectroscopic MRI. By directly optimizing
      the shape of the spatial response function (SRF), the new method accounts for
      coil sensitivity variation across individual voxels and their side lobes. In this
      fashion, it mitigates the signal contamination and side-lobe aliasing, to which
      previous techniques are susceptible at low resolution. Although the computational
      burden is higher, minimum-norm reconstruction is shown to be feasible using an
      iterative algorithm. Benefits in terms of SRF shape and artifact suppression are
      demonstrated.

PMID- 16408282
TI  - Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla:
      detection of high GABA concentrations.
AB  - Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the
      substantia nigra (SN), the cause of which is unknown. Characterization of early
      SN pathology could prove beneficial in the treatment and diagnosis of PD. The
      present study shows that with the use of short-echo (5 ms) Stimulated-Echo
      Acquisition Mode (STEAM) spectroscopy and LCModel, a neurochemical profile
      consisting of 10 metabolites, including gamma-aminobutyric acid (GABA), glutamate
      (Glu), and glutathione (GSH), can be measured from the unilateral SN at 4 tesla.
      The neurochemical profile of the SN is unique and characterized by a fourfold
      higher GABA/Glu ratio compared to the cortex, in excellent agreement with
      established neurochemistry. The presence of elevated GABA levels in SN was
      validated with the use of editing, suggesting that partial volume effects were
      greatly reduced. These findings establish the feasibility of obtaining a
      neurochemical profile of the unilateral human SN by single-voxel spectroscopy in
      small volumes.

PMID- 16408283
TI  - Sliding multislice (SMS): a new technique for minimum FOV usage in axial
      continuously moving-table acquisitions.
AB  - A novel technique for axial continuously moving-table scans is described that
      minimizes the required extension of the scanner's field of view (FOV) along the
      direction of table motion (z) by applying a segmented multislice acquisition
      technique. Any anatomical slice is acquired by applying the same phase-encoding
      steps at the same spatial positions along the scanner FOV. The full k-space data
      set of any anatomical slice is collected while the slice moves through the
      scanner from one scan position to the next. Simultaneous acquisition of multiple
      slices is realized by shifting the acquisition trajectories of different slices
      in time. It is demonstrated how the image artifact behavior that relates to
      varying imaging properties along the distance the table traverses during the
      acquisition of any given anatomical slice can be optimized simultaneously for all
      images. Discontinuities between the images along the slice axis are avoided
      because all z-dependent scan properties are encoded identically for all slices.
      Flexible spatial acquisition patterns are proposed to enable data oversampling
      and overlapping slice acquisitions at reduced table speeds. A framework of
      equations is presented by which matched parameter combinations for sliding
      multislice acquisitions can be applied to both single- and multiecho sequences.
      The new technique is validated on phantom and in vivo measurements using a T1
      weighted fast low-angle shot (FLASH) sequence as well as a T2-weighted multi-spin
      echo sequence of variable echo train lengths.

PMID- 16408284
TI  - Mohawk is a novel homeobox gene expressed in the developing mouse embryo.
AB  - Homeodomain-containing proteins comprise a superfamily of transcription factors
      that participate in the regulation of almost all aspects of embryonic
      development. Here, we describe the mouse embryonic expression pattern of Mohawk,
      a new member of the TALE superclass of atypical homeobox genes that is most
      closely related to the Iroquois class. During mouse development, Mohawk was
      transcribed in cell lineages derived from the somites. As early as embryonic day
      9.0, Mohawk was expressed in an anterior to posterior gradient in the dorsomedial
      and ventrolateral lips of the dermomyotome of the somites that normally give rise
      to skeletal muscle. Mohawk transcription in the dorsomedial region required the
      expression of the transcription factor paraxis. As somites matured, Mohawk
      transcription was observed in the tendon-specific syndetome and the sclerotome
      derived condensing mesenchyme that prefigures the proximal ribs and vertebral
      bodies. In the limbs, Mohawk was expressed in a pattern consistent with the
      developing tendons that form along the dorsal and ventral aspect of the
      phalanges. Finally, Mohawk was detectable in the tips of the ureteric buds in the
      metanephric kidneys and the testis cords of the male gonad. Together, these
      observations suggest that Mohawk is an important regulator of vertebrate
      development.

PMID- 16408285
TI  - microRNAs under the microscope.
AB  - Once regarded as a biological anomaly, microRNAs (miRNAs) have since been
      recognized as a prevalent RNA species that regulates a wide array of biological
      processes, from fat storage and insulin secretion, to apoptosis and cell growth.
      Recent studies show that miRNAs are expressed at precise times and locations in
      embryonic development. Moreover, disruption of miRNA processing triggers
      widespread developmental defects. These findings bolster the idea that miRNAs
      also regulate multiple aspects of embryonic development. This primer focuses on
      the emerging roles of miRNAs in development. The basics of miRNA biogenesis and
      miRNA and mRNA target identification are covered, with an emphasis on miRNA
      function in development. The primer also features a dialog about current topics
      in the field.

PMID- 16408286
TI  - Craniofacial development in marsupial mammals: developmental origins of
      evolutionary change.
AB  - Biologists have long studied the evolutionary consequences of the differences in
      reproductive and life history strategies of marsupial and eutherian mammals. Over
      the past few decades, the impact of these strategies on the development of the
      marsupial embryo and neonate has received attention. In this review, the
      differences in development in the craniofacial region in marsupial and eutherian
      mammals will be discussed. The review will highlight differences at the
      organogenic and cellular levels, and discuss hypotheses for shifts in the
      expression of important regulatory genes. The major difference in the organogenic
      period is a whole-scale shift in the relative timing of central nervous system
      structures, in particular those of the forebrain, which are delayed in
      marsupials, relative to the structures of the oral-facial apparatus. Correlated
      with the delay in development of nervous system structures, the ossification of
      the bones of the neurocranium are delayed, while those of the face are
      accelerated. This study will also review work showing that the neural crest,
      which provides much of the cellular material to the facial skeleton and may also
      carry important patterning information, is notably accelerated in its development
      in marsupials. Potential consequences of these observations for hypotheses on
      constraint, evolutionary integration, and the existence of developmental modules
      is discussed. Finally, the implications of these results for hypotheses on the
      genetic modulation of craniofacial patterning are presented.

PMID- 16408288
TI  - Comparative genomic and expression analysis of group B1 sox genes in zebrafish
      indicates their diversification during vertebrate evolution.
AB  - Group B1 Sox genes encode HMG domain transcription factors that play major roles
      in neural development. We have identified six zebrafish B1 sox genes, which
      include pan-vertebrate sox1a/b, sox2, and sox3, and also fish-specific sox19a/b.
      SOX19A/B proteins show a transcriptional activation potential that is similar to
      other B1 SOX proteins. The expression of sox19a and sox3 begins at approximately
      the 1,000-cell stage during embryogenesis and becomes confined to the future
      ectoderm by the shield stage. This is reminiscent of the epiblastic expression of
      Sox2 and/or Sox3 in amniotes. As development progresses, these six B1 sox genes
      display unique expression patterns that overlap distinctly from one region to
      another. sox19a expression is widespread in the early neuroectoderm, resembling
      pan-neural Sox2 expression in amniotes, whereas zebrafish sox2 shows anterior
      restricted expression. Comparative genomics suggests that sox19a/b and mammalian
      Sox15 (group G) have an orthologous relationship and that the B1/G Sox genes
      arose from a common ancestral gene through two rounds of genome duplication. It
      seems likely, therefore, that each B1/G Sox gene has gained a distinct expression
      profile and function during vertebrate evolution.

PMID- 16408289
TI  - Serotonin and fluoxetine modulate bone cell function in vitro.
AB  - Recent studies have proposed a role for serotonin and its transporter in
      regulation of bone cell function. In the present study, we examined the in vitro
      effects of serotonin and the serotonin transporter inhibitor fluoxetine "Prozac"
      on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into
      osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected
      the total number of differentiated osteoclasts as well as bone resorption in a
      bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several
      serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in
      serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also
      found in murine osteoblasts and osteoclasts, indicating an ability to produce
      serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine
      affected proliferation and NFkappaB activity in a biphasic manner. Proliferation
      of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A
      receptor expression was enhanced by serotonin. Fluoxetine stimulated
      proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations,
      microM concentrations were inhibitory. The effect of fluoxetine seemed direct,
      probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1
      cells was inhibited by the PKC inhibitor (GF109203) and was also markedly reduced
      when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were added.
      Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF
      kappaB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast
      induced inhibition of osteoclast differentiation, whereas fluoxetine had the
      opposite effect. This study further describes possible mechanisms by which
      serotonin and the serotonin transporter can affect bone cell function.

PMID- 16408287
TI  - Reinnervation of hair cells by auditory neurons after selective removal of spiral
      ganglion neurons.
AB  - Hearing loss can be caused by primary degeneration of spiral ganglion neurons or
      by secondary degeneration of these neurons after hair cell loss. The replacement
      of auditory neurons would be an important step in any attempt to restore auditory
      function in patients with damaged inner ear neurons or hair cells. Application of
      beta-bungarotoxin, a toxin derived from snake venom, to an explant of the cochlea
      eradicates spiral ganglion neurons while sparing the other cochlear cell types.
      The toxin was found to bind to the neurons and to cause apoptotic cell death
      without affecting hair cells or other inner ear cell types as indicated by TUNEL
      staining, and, thus, the toxin provides a highly specific means of
      deafferentation of hair cells. We therefore used the denervated organ of Corti
      for the study of neuronal regeneration and synaptogenesis with hair cells and
      found that spiral ganglion neurons obtained from the cochlea of an untreated
      newborn mouse reinnervated hair cells in the toxin-treated organ of Corti and
      expressed synaptic vesicle markers at points of contact with hair cells. These
      findings suggest that it may be possible to replace degenerated neurons by
      grafting new cells into the organ of Corti.

PMID- 16408290
TI  - PLC-beta2 monitors the drug-induced release of differentiation blockade in
      tumoral myeloid precursors.
AB  - The differentiation therapy in treatment of acute promyelocytic leukemia (APL),
      based on the administration of all-trans retinoic acid (ATRA), is currently
      flanked with the use of As2O3, a safe and effective agent for patients showing a
      resistance to ATRA treatment. A synergy between ATRA and As3O3 was also reported
      in inducing granulocytic differentiation of APL-derived cells. We have
      demonstrated that phospholipase C-beta2 (PLC-beta2), highly expressed in
      neutrophils and nearly absent in tumoral promyelocytes, largely increases during
      ATRA treatment of APL-derived cells and strongly correlates with the
      responsiveness of APL patients to ATRA-based differentiating therapies. Here we
      report that, in APL-derived cells, low doses of As3O3 induce a slight increase of
      PLC-beta2 together with a moderate maturation, and cooperate with ATRA to provoke
      a significant increase of PLC-beta2 expression. Remarkably, the amounts of PLC
      beta2 draw a parallel with the differentiation levels reached by both ATRA
      responsive and -resistant cells treated with ATRA/As2O3 combinations. PLC-beta2
      is not necessary for the progression of tumoral promyelocytes along the
      granulocytic lineage and is unable to overcome the differentiation block or to
      potentiate the agonist-induced maturation. On the other hand, since its
      expression closely correlates with the differentiation level reached by APL
      derived cells induced to maturate by drugs presently employed in APL therapies,
      PLC-beta2 represents indeed a specific marker to test the ability of
      differentiation agents to induce the release of the maturation blockade of
      tumoral myeloid precursors.

PMID- 16408291
TI  - Targeting the NF-kappa B pathway in estrogen receptor negative MDA-MB-231 breast
      cancer cells using small inhibitory RNAs.
AB  - Cancer cells in order to survive are often mutated to block apoptosis. One
      chemotherapeutic option is the re-establishment of apoptosis. An example of such
      a therapy is the PKC inhibitor Go6976, which activates apoptosis and shrinks in
      vivo tumors in estrogen receptor-negative breast cancers. We proposed as a
      mechanism blockage of activation of the transcription factor NF-kappaB, which is
      anti-apoptotic and often elevated in cancers. Over recent years, questions have
      arisen regarding the specificity of these "small-molecule inhibitors." We have
      therefore explored the role of NF-kappaB inhibition in MDA-MB-231 breast cancer
      cells using small inhibitory RNAs (siRNA). siRNAs designed against NF-kappaB
      protein p65 (RelA) and IKKalpha, IKKbeta, and IKKgamma, strongly decreased the
      target proteins. But, unlike Go6976, they did not decrease basal NF-kappaB or
      cause apoptosis. In particular, the decrease in p65 protein had no effects on
      apoptosis or cell proliferation, thus questioning the importance of NF-kappaB
      alone in the maintenance of these cells. Furthermore, the proteasome inhibitor MG
      132 caused loss of IkappaBalpha, and an increase of it is phosphorylated form,
      but basal NF-kappaB was unchanged, whilst activation of NF-kappaB by TNFalpha was
      completely inhibited, suggesting that MG-132 activity is independent of
      constitutive NF-kappaB activation. We ascribe these differences to the
      specificity of inhibition by siRNAs as compared to the well-known non-specificity
      of small-molecule inhibitors. We conclude that the mutations in these cancer
      cells made them resistant to apoptosis, by elevating their NF-kappaB and
      activating other basal pathways that are blocked by Go6976 but not by IKK and p65
      siRNAs.

PMID- 16408292
TI  - In vivo photothermal flow cytometry: imaging and detection of individual cells in
      blood and lymph flow.
AB  - Flow cytometry is a well-established, powerful technique for studying cells in
      artificial flow in vitro. This review covers a new potential application of this
      technique for studying normal and abnormal cells in their native condition in
      blood or lymph flow in vivo. Specifically, the capabilities of the label-free
      photothermal (PT) technique for detecting and imaging cells in the microvessel
      network of rat mesentery are analyzed from the point of view of overcoming the
      problems of flow cytometry in vivo. These problems include, among others, the
      influences of light scattering and absorption in vessel walls and surrounding
      tissues, instability of cell velocity, and cells numbers and positions in a
      vessel's cross-section. The potential applications of this new approach in cell
      biochemistry and medicine are discussed, including molecular imaging; studying
      the metabolism and pathogenesis of many diseases at a cellular level; and
      monitoring and quantifying metastatic and apoptotic cells, and/or their responses
      to therapeutic interventions (e.g., drug or radiation), in natural biological
      environments.

PMID- 16408294
TI  - Effects of 24R,25- and 1alpha,25-dihydroxyvitamin D3 on mineralizing growth plate
      chondrocytes.
AB  - Time- and dosage-dependent effects of 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3) on
      primary cultures of pre- and post-confluent avian growth plate (GP) chondrocytes
      were examined. Cultures were grown in either a serum-containing culture medium
      designed to closely mimic normal GP extracellular fluid (DATP5) or a commercially
      available serum-free media (HL-1) frequently used for studying skeletal cells.
      Hoechst DNA, Lowry protein, proteoglycan (PG), lactate dehydrogenase (LDH), and
      alkaline phosphatase (ALP) activity and calcium and phosphate mineral deposition
      in the extracellular matrix were measured. In preconfluent cultures grown in
      DATP5, physiological levels of 24,25(OH)(2)D(3) (0.10-10 nM) increased DNA,
      protein, and LDH activity significantly more than did 1,25(OH)(2)D(3) (0.01-1.0
      nM). However, in HL-1, the reverse was true. Determining ratios of LDH and PG to
      DNA, protein, and each other, revealed that 1,25(OH)(2)D(3) specifically
      increased PG, whereas 24,25(OH)(2)D(3) increased LDH. Post-confluent cells were
      generally less responsive, especially to 24,25(OH)(2)D(3). The positive anabolic
      effects of 24,25(OH)(2)D(3) required serum-containing GP-fluid-like culture
      medium. In contrast, effects of 1,25(OH)(2)D(3) were most apparent in serum-free
      medium, but were still significant in serum-containing media. Administered to
      preconfluent cells in DATP5, 1,25(OH)(2)D(3) caused rapid, powerful, dosage
      dependent inhibition of Ca(2+) and Pi deposition. The lowest level tested (0.01
      nM) caused >70% inhibition during the initial stages of mineral deposition;
      higher levels of 1,25(OH)(2)D(3) caused progressively more profound and
      persistent reductions. In contrast, 24,25(OH)(2)D(3) increased mineral deposition
      20-50%; it required >1 week, but the effects were specific, persistent, and
      largely dosage-independent. From a physiological perspective, these effects can
      be explained as follows: 1,25(OH)(2)D(3) levels rise in hypocalcemia; it
      stimulates gut absorption and releases Ca(2+) from bone to correct this
      deficiency. We now show that 1,25(OH)(2)D(3) also conserves Ca(2+) by inhibiting
      mineralization. The slow anabolic effects of 24,25(OH)(2)D(3)are consistent with
      its production under eucalcemic conditions which enable bone formation. These
      findings, which implicate serum-binding proteins and accumulation of PG in
      modulating accessibility of the metabolites to GP chondrocytes, also help explain
      some discrepancies previously reported in the literature.

PMID- 16408293
TI  - High glucose increases extracellular matrix production in pancreatic stellate
      cells by activating the renin-angiotensin system.
AB  - Pancreatic stellate cells (PSCs) are involved in pancreatic inflammation and
      fibrosis. Recent studies have shown that blocking the renin-angiotensin system
      (RAS) attenuates pancreatic inflammation and fibrosis. However, there are few
      data about the direct effects of high glucose on extracellular matrix (ECM)
      protein synthesis and angiotensin II (Ang II) induction in PSCs. PSCs were
      isolated from male Sprague-Dawley rats and cultured in medium containing 5.5 mM
      (LG group) or 27 mM D-glucose (HG group). Levels of Ang II and transforming
      growth factor-beta (TGF-beta) in culture media were measured and Ang II-positive
      cells were counted. We used real-time polymerase chain reaction (PCR) to detect
      Ang II receptor expression and Western blot analysis for the expression of ECM
      proteins such as connective-tissue growth factor (CTGF) and collagen type IV.
      Cells were also treated with an Ang II-receptor antagonist (candesartan, 10
      microM) or angiotensin-converting enzyme (ACE) inhibitor (ramiprilat, 100 nM).
      Thymidine uptake by PSCs increased fourfold with high glucose treatment. Ang II
      levels and the proportion of Ang II-positive PSCs were significantly increased
      after 6 h under high-glucose conditions. TGF-beta concentrations also increased
      significantly with high glucose. After 72 h, the expression of CTGF and collagen
      type IV proteins in high-glucose cultures increased significantly and this
      increase was effectively attenuated by the candesartan or the ramiprilat. All
      together, high glucose induced PSCs proliferation and ECM protein synthesis, and
      these effects were attenuated by an Ang II-receptor antagonist. The data suggest
      that pancreatic inflammation and fibrosis aggravated by hyperglycemia, and Ang II
      play an important role in this pathogenesis.

PMID- 16408295
TI  - Microinjection of an antibody against the cysteine-protease involved in male
      chromatin remodeling blocks the development of sea urchin embryos at the initial
      cell cycle.
AB  - We reported recently that the inhibition of cysteine-proteases with E-64-d
      disturbs DNA replication and prevents mitosis of the early sea urchin embryo.
      Since E-64-d is a rather general inhibitor of thiol-proteases, to specifically
      target the cysteine-protease previously identified in our laboratory as the
      enzyme involved in male chromatin remodeling after fertilization, we injected
      antibodies against the N-terminal sequence of this protease that were able to
      inhibit the activity of this enzyme in vitro. We found that injection of these
      antibodies disrupts the initial zygotic cell cycle. As shown in this report in
      injected zygotes a severe inhibition of DNA replication was observed, the mitotic
      spindle was not correctly bipolarized the embryonic development was aborted at
      the initial cleavage division. Consequently, the injection of these antibodies
      mimics perfectly the effects previously described for E-64-d, indicating that the
      effects of this inhibitor rely mainly on the inhibition of the cysteine-protease
      involved in male chromatin remodeling after fertilization. These results further
      support the crucial role of this protease in early embryonic development.

PMID- 16408296
TI  - Transcriptional profiling of brain-derived-neurotrophic factor-induced neuronal
      plasticity: a novel role for nociceptin in hippocampal neurite outgrowth.
AB  - Brain derived neurotrophic factor (BDNF) exhibits a sequence of actions on
      neurons ranging from acute enhancement of transmission to long-term promotion of
      neurite outgrowth and synaptogenesis associated with learning and memory. The
      manifold effects of BDNF on neuronal modifications may be mediated by genomic
      alterations. We previously found that BDNF treatment acutely increases
      transcription of the synaptic vesicle protein Rab3A, required for trophin-induced
      synaptic plasticity, as well as the peptide VGF, which increases during learning.
      To elucidate comprehensive transcriptional programs associated with short- and
      long-term BDNF exposure, we now examine mRNA abundance and complexity using
      Affymetrix GeneChips in cultured hippocampal neurons. Consistent with the
      modulation of synaptic plasticity, BDNF treatment (3-6 h) induced mRNAs encoding
      the synapse-associated proteins synaptojanin 2, neuronal pentraxin 1, septin 9,
      and ryanodine receptor 2. BDNF also induced expression of mRNAs encoding
      neuropeptides (6-12 h), including prepronociceptin, neuropeptide Y, and
      secretogranin. To determine whether these neuropeptides induced by BDNF mediate
      neuronal development, we examined their effects on hippocampal neurons. The four
      mature peptides derived from post-translational processing of the ppNociceptin
      propeptide induced the expression of several immediate early genes in hippocampal
      cultures, indicating neuronal activation. To examine the significance of
      activation, the effects of nociceptin (orphanin FQ) and nocistatin on neurite
      outgrowth were examined. Quantitative morphometric analysis revealed that
      nociceptin significantly increased both average neurite length and average number
      of neurites per neuron, while nocistatin had no effect on these parameters. These
      results reveal a novel role for nociceptin and suggest that these neuropeptide
      systems may contribute to the regulation of neuronal function by BDNF.

PMID- 16408297
TI  - Severe deficits in 5-HT2A -mediated neurotransmission in BDNF conditional mutant
      mice.
AB  - BDNF is thought to provide critical trophic support for serotonin neurons. In
      order to determine postnatal effects of BDNF on the serotonin system, we examined
      a line of conditional mutant mice that have normal brain content of BDNF during
      prenatal development but later depletion of this neurotrophin in the postnatal
      period. These mice show a behavioral phenotype that suggests serotonin
      dysregulation. However, as shown here, the presynaptic serotonin system in the
      adult conditional mutant mice appeared surprisingly normal from histological,
      biochemical, and electrophysiological perspectives. By contrast, a dramatic and
      unexpected postsynaptic 5-HT2A deficit in the mutant mice was found.
      Electrophysiologically, serotonin neurons appeared near normal except, most
      notably, for an almost complete absence of expected 5-HT2A -mediated glutamate
      and GABA postsynaptic potentials normally displayed by these neurons. Further
      analysis showed that BDNF mutants had much reduced 5-HT2A receptor protein in
      dorsal raphe nucleus and a similar deficit in prefrontal cortex, a region that
      normally shows a high level of 5-HT2A receptor expression. Recordings in
      prefrontal slice showed a marked deficit in 5-HT2A -mediated excitatory
      postsynaptic currents, similar to that seen in the dorsal raphe. These findings
      suggest that postnatal levels of BDNF play a relatively limited role in
      maintaining presynaptic aspects of the serotonin system and a much greater role
      in maintaining postsynaptic 5-HT2A and possibly other receptors than previously
      suspected.

PMID- 16408298
TI  - Rescue percutaneous coronary intervention for failed thrombolysis.
AB  - BACKGROUND: Previous studies of rescue percutaneous coronary intervention (PCI)
      for failed thrombolysis yielded conflicting results. In the current era of newer
      thrombolytic agents, coronary stents, glycoprotein IIb/IIIa inhibitors, and
      aggressive hemodynamic support, the outcome of this high-risk patient group has
      not been characterized. METHODS: From January 2000 to October 2004, 214
      consecutive patients were transferred and underwent emergent coronary angiography
      following failed thrombolysis. One hundred and fifty five (72%) underwent
      immediate PCI, 23 (11%) underwent delayed PCI, and 36 (17%) received surgical
      revascularization or medical therapy. Medical records and angiograms for the
      entire PCI cohort (n=178) were reviewed for in-hospital events including bleeding
      complications, stroke, recurrent ischemia or myocardial infarction (MI), target
      vessel revascularization (TVR), and death. RESULTS: Time from symptom onset to
      thrombolysis (mean +/- standard deviation) was 5.6 +/- 11.9 hr, and time from
      thrombolysis to angiography was 7.0 +/- 5.5 hr. The study cohort was critically
      ill, with 9.6% experiencing cardiac arrest, 21% in cardiogenic shock, and 12%
      intubated prior to transfer. Coronary stents were placed in 88%, Rheolytic
      thrombectomy was used in 21%, an intraaortic balloon pump was placed in 17%, and
      a glycoprotein IIb/IIIa inhibitor was administered in 92%. Patients receiving
      delayed PCI had higher TIMI 3 flow grade at initial angiography than those
      receiving immediate PCI (83% vs. 34%, respectively, P < 0.0001). Angiographic
      success was 90% for the entire PCI cohort, 89% for the immediate PCI group, and
      100% for the delayed PCI group. Clinical success (angiographic success and
      freedom from major adverse cardiac events) was 85% for the entire PCI cohort, 83%
      for the immediate PCI group, and 100% for the delayed PCI group. Severe and
      moderate bleeding complications occurred in 7.3%, stroke in 1.7%, recurrent
      ischemia or MI in 7.3%, and TVR in 3.4%. Overall, in-hospital mortality for the
      entire PCI cohort was 3.4%. CONCLUSIONS: This observational, consecutive, real
      world study of contemporary rescue PCI for failed thrombolysis shows a high use
      of coronary stents, Rheolytic thrombectomy, glycoprotein IIb/IIIa inhibitors, and
      intraaortic balloon pump placement. Angiographic and clinical success was high
      with low bleeding complications and low in-hospital mortality, suggesting that
      prospective, randomized trials using contemporary interventional therapy for
      rescue PCI be considered.

PMID- 16408299
TI  - Functional and clinical outcomes of nitinol stenting with and without abciximab
      for complex superficial femoral artery disease: a randomized trial.
AB  - OBJECTIVE: To evaluate the effect of glycoprotein IIb/IIIa inhibition during
      nitinol stenting, of superficial femoral occlusive disease. BACKGROUND: Stent
      implantation in the superficial femoral artery has been associated with
      suboptimal results while Glycoprotein IIb/IIIa inhibitors have shown improved
      procedural results during coronary intervention. We evaluated abciximab infusion
      during (Smart Stent) implantation in superficial femoral obstructions. METHODS:
      We conducted a randomized placebo controlled trial. The two primary end points
      include: (1) 9-month restenosis defined as a decrease in ankle brachial index and
      in-stent duplex ultrasound restenosis: (2) adverse events defined as death (30
      days) or repeat revascularization within 9 months. RESULTS: Twenty-seven patients
      were randomized to abciximab and 24 patients to control (placebo). The primary
      end point of cumulative restenosis occurred in 15.4% of patients administered
      abciximab and in 12% administered placebo (P = 0.873). The primary restenosis
      endpoint in diabetics and total occlusions were similar at 14.3% and 15.4%
      respectively. The composite end point of 30-day mortality and 9-month
      revascularization occurred in 5.8% abciximab and 0% (P = 0.274) placebo with no
      30-day deaths. Graded treadmill time and Rutherford class were all significantly
      improved in both groups, but the abciximab group did not appear to demonstrate
      any identifiable effect. CONCLUSION: (Smart Stent) nitinol stenting of the
      superficial femoral artery was associated with favorable functional outcomes at 9
      months. Adjunctive abciximab did not appear to demonstrate any identifiable
      effect.

PMID- 16408300
TI  - Isolation of epithelial stem cells from dermis by a three-dimensional culture
      system.
AB  - Skin is a representative self-renewing tissue containing stem cells. Although
      many attempts have been made to define and isolate skin-derived stem cells,
      establishment of a simple and reliable isolation procedure remains a goal to be
      achieved. Here, we report the isolation of cells having stem cell properties from
      mouse embryonic skin using a simple selection method based on an assumption that
      stem cells may grow in an anchorage-independent manner. We inoculated single cell
      suspensions prepared from mouse embryonic dermis into a temperature-sensitive gel
      and propagated the resulting colonies in a monolayer culture. The cells named
      dermis-derived epithelial progenitor-1 (DEEP) showed epithelial morphology and
      grew rapidly to a more than 200 population doubling level over a period of 250
      days. When the cells were kept confluent, they spontaneously formed spheroids and
      continuously grew even in spheroids. Immunostaining revealed that all of the
      clones were positive for the expression of cytokeratin-8, -18, -19, and E
      cadherin and negative for the expression of cytokeratin-1, -5, -6, -14, -20,
      vimentin, nestin, a ckit. Furthermore, they expressed epithelial stem cell
      markers such as p63, integrin beta1, and S100A6. On exposure to TGFbeta in
      culture, some of DEEP-1 cells expressed alpha-smooth muscle actin. When the cells
      were transplanted into various organs of adult SCID mice, a part of the
      inoculated cell population acquired neural, hepatic, and renal cell properties.
      These results indicate that the cells we isolated were of epithelial stem cell
      origin and that our new approach is useful for isolation of multipotent stem
      cells from skin tissues.

PMID- 16408301
TI  - Gangliosides of the nuclear membrane: a crucial locus of cytoprotective
      modulation.
AB  - The original concept of gangliosides as localized components of the plasma
      membrane has broadened in recent years with recognition of their presence in
      various intracellular pools as well. The nuclear envelope (NE), consisting of two
      unique membranes, is one such structure shown to contain members of the
      gangliotetraose family and possibly other sialoglycolipids. GM1 situated in the
      inner membrane of the NE is tightly associated with a Na+/Ca2+ exchanger whose
      activity it potentiates in the transfer of Ca2+ from nucleoplasm to the NE lumen.
      This is in contrast to Na+/Ca2+ exchangers of the plasma membrane which bind GM1
      less avidly or not at all. This is believed due to different isoforms of
      exchanger, and a difference in topology of the exchanger relative to GM1.
      Cultured neurons from mice genetically engineered to lack gangliotetraose
      gangliosides such as GM1 were highly vulnerable to Ca2+-induced apoptosis. They
      were rescued to some extent by GM1 but more effectively by LIGA-20, a membrane
      permeant derivative of GM1 that traverses the plasma membrane more effectively
      than GM1 and inserts into the NE. As further indication of Ca2+ dysregulation,
      the mutant mice were highly susceptible to kainite-induced seizures which were
      attenuated by LIGA-20. This correlated with the ability of LIGA-20 to cross the
      blood-brain barrier, enter brain cells, insert into the NE, and potentiate the
      nuclear exchanger. GM1 in the NE, in association with nuclear Na+/Ca2+ exchanger,
      is thus seen as contributing to Ca2+ regulation within the nucleus and in the
      process exerting a cytoprotective role.

PMID- 16408302
TI  - Changes within maturing neurons limit axonal regeneration in the developing
      spinal cord.
AB  - Embryonic birds and mammals display a remarkable ability to regenerate axons
      after spinal injury, but then lose this ability during a discrete developmental
      transition. To explain this transition, previous research has emphasized the
      emergence of myelin and other inhibitory factors in the environment of the spinal
      cord. However, research in other CNS tracts suggests an important role for neuron
      intrinsic limitations to axon regeneration. Here we re-examine this issue
      quantitatively in the hindbrain-spinal projection of the embryonic chick. Using
      heterochronic cocultures we show that maturation of the spinal cord environment
      causes a 55% reduction in axon regeneration, while maturation of hindbrain
      neurons causes a 90% reduction. We further show that young neurons transplanted
      in vivo into older spinal cord can regenerate axons into myelinated white matter,
      while older axons regenerate poorly and have reduced growth cone motility on a
      variety of growth-permissive ligands in vitro, including laminin, L1, and N
      cadherin. Finally, we use video analysis of living growth cones to directly
      document an age-dependent decline in the motility of brainstem axons. These data
      show that developmental changes in both the spinal cord environment and in
      brainstem neurons can reduce regeneration, but that the effect of the environment
      is only partial, while changes in neurons by themselves cause a nearly complete
      reduction in regeneration. We conclude that maturational events within neurons
      are a primary cause for the failure of axon regeneration in the spinal cord.

PMID- 16408303
TI  - Cytoplasmic domain of protocadherin-alpha enhances homophilic interactions and
      recognizes cytoskeletal elements.
AB  - Cell adhesion molecules of the protocadherin-alpha (pcdh-alpha), -beta, and 
      gamma families have been proposed to be synaptic specifiers. Pcdh-alpha and 
      gamma family members localize in part to synapses, and deletion of all pcdh
      gammas in mouse affects synaptogenesis. Little is known, however, about the
      binding specificities and intracellular signaling of protocadherins. Using
      heterologous expression of tagged constructs, immunostaining, and biotinylation
      of surface components followed by Western blots we demonstrate that pcdh-alphas
      undergo homophilic interactions that are significantly enhanced by the
      cytoplasmic domain. Pcdh-alphas cloned from chick ciliary ganglion have one of
      two cytoplasmic constant regions (A- and B-types). Screening a yeast two-hybrid
      library of ciliary ganglion cDNA with the A-type domain yielded a fragment of
      neurofilament M (NFM); screening with B-type domain yielded a fragment of the
      actin-bundling protein fascin. Cotransfection of HEK cells with the constructs
      indicated that the NFM and A-type fragments codistributed as did the fascin and B
      type fragments, and the latter could be coimmunoprecipitated. Antibody-induced
      clustering of full-length pcdh-alphas on the surface of transfected HEK cells
      induced coclustering of the interacting NFM fragment. Native full-length NFM in
      tissue extracts bound specifically to the A-type domain on beads, while native
      full-length fascin in tissue extracts specifically coimmunoprecipitated with pcdh
      alpha. Immunostaining neurons demonstrated codistribution of full-length pcdh
      alpha with both NFM and actin filaments. These findings suggest cytoskeletal
      links for pcdh-alphas and identify candidate targets. They also demonstrate
      homophilic interactions for pcdh-alphas as described for classical cadherins.

PMID- 16408304
TI  - Ndrg4 enhances NGF-induced ERK activation uncoupled with Elk-1 activation.
AB  - Ndrg4 is expressed predominantly in the early postnatal rat brain and may be
      related to neural cell differentiation. PC12 cell lines stably expressing
      increased levels of Ndrg4 protein display enhanced NGF-induced phosphorylation of
      MEK and ERK. In contrast, the Ndrg4-C2-overexpressed PC12 cell lines showed
      attenuated NGF-promoted phosphorylation of Elk-1, which is a nuclear target of
      ERK. A reporter assay also indicated that Ndrg4-C2 suppresses Elk-1-mediated
      transcriptional activation and SRE reporter expression. The suppressive effect of
      Ndrg4-C2 on NGF-induced activation of Elk-1 was abolished by colchicine but not
      by cytochalasin D, suggesting that microtubules are involved in the reduced
      activation of Elk-1 by Ndrg4. Ndrg4 may play a role in supporting the activation
      of ERK and its target proteins needed for neuronal differentiation and in
      reducing the activation of Elk-1 implicated in cell growth.

PMID- 16408306
TI  - Kinesin-2 differentially regulates the anterograde axonal transports of
      acetylcholinesterase and choline acetyltransferase in Drosophila.
AB  - Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are involved in
      acetylcholine synthesis and degradation at pre- and postsynaptic compartments,
      respectively. Here we show that their anterograde transport in Drosophila larval
      ganglion is microtubule-dependent and occurs in two different time profiles. AChE
      transport is constitutive while that of ChAT occurs in a brief pulse during third
      instar larva stage. Mutations in the kinesin-2 motor subunit Klp64D and separate
      siRNA-mediated knock-outs of all the three kinesin-2 subunits disrupt the ChAT
      and AChE transports, and these antigens accumulate in discrete nonoverlapping
      punctae in neuronal cell bodies and axons. Quantification analysis further showed
      that mutations in Klp64D could independently affect the anterograde transport of
      AChE even before that of ChAT. Finally, ChAT and AChE were coimmunoprecipitated
      with the kinesin-2 subunits but not with each other. Altogether, these suggest
      that kinesin-2 independently transports AChE and ChAT within the same axon. It
      also implies that cargo availability could regulate the rate and frequency of
      transports by kinesin motors.

PMID- 16408305
TI  - Genome-wide P-element screen for Drosophila synaptogenesis mutants.
AB  - A molecular understanding of synaptogenesis is a critical step toward the goal of
      understanding how brains "wire themselves up," and then "rewire" during
      development and experience. Recent genomic and molecular advances have made it
      possible to study synaptogenesis on a genomic scale. Here, we describe the
      results of a screen for genes involved in formation and development of the
      glutamatergic Drosophila neuromuscular junction (NMJ). We screened 2185 P-element
      transposon mutants representing insertions in approximately 16% of the entire
      Drosophila genome. We first identified recessive lethal mutants, based on the
      hypothesis that mutations causing severe disruptions in synaptogenesis are likely
      to be lethal. Two hundred twenty (10%) of all insertions were homozygous lethal.
      Two hundred five (93%) of these lethal mutants developed at least through late
      embryogenesis and formed neuromusculature. We examined embryonic/larval NMJs in
      202 of these homozygous mutants using immunocytochemistry and confocal
      microscopy. We identified and classified 88 mutants with altered NMJ morphology.
      Insertion loci in these mutants encode several different types of proteins,
      including ATP- and GTPases, cytoskeletal regulators, cell adhesion molecules,
      kinases, phosphatases, RNA regulators, regulators of protein formation,
      transcription factors, and transporters. Thirteen percent of insertions are in
      genes that encode proteins of novel or unknown function. Complementation tests
      and RT-PCR assays suggest that approximately 51% of the insertion lines carry
      background mutations. Our results reveal that synaptogenesis requires the
      coordinated action of many different types of proteins--perhaps as much as 44% of
      the entire genome--and that transposon mutageneses carry important caveats that
      must be respected when interpreting results generated using this method.

PMID- 16408307
TI  - Influence of retinoic acid and lithium on proliferation and dopaminergic
      potential of human NT2 cells.
AB  - Our laboratory is working with the human NTera2/D1 (NT2) cell line, which has
      properties similar to those of progenitor cells in the central nervous system
      (CNS). These neural-like precursor cells can differentiate into all three major
      lineages, neurons, astrocytes, and oligodendrocytes. The pure neuronal
      population, hNT neurons, possess characteristics of dopamine (DA) cells. First,
      we analyzed whether the retinoic acid (RA)-treated hNT neurons and the NT2
      precursor cells expressed two transcription factors required for development of
      the midbrain DA neurons. We report that NT2 cells endogenously expressed
      Engrailed-1 and Ptx3, whereas RA-treated hNT neurons did not express Engrailed-1
      or Ptx3. Next we examined the influence of lithium treatment on Engrailed-1 and
      Ptx3 as well as another critical transcription factor, Nurr1. Previous research
      has shown that lithium can mimic the Wnt pathway, which is important for the
      induction of these transcription factors. Finally, we investigated the effect of
      lithium treatment on the viability and proliferation of NT2 cells, because
      lithium has been shown to stimulate neurogenesis in adult neural precursors.
      Lithium treatment increased the viability and proliferation of NT2 cells. The
      expression of transcription factors essential for the induction and maintenance
      of the DA phenotype was not increased in NT2 after lithium treatment. We conclude
      that the NT2 cell line is an excellent in vitro model system for studying the
      influence of pharmalogical agents on proliferation, differentiation, and
      apoptosis of a human neural progenitor cell line.

PMID- 16408308
TI  - Multifunctional carbon nanofibers with conductive, magnetic and superhydrophobic
      properties.

PMID- 16408309
TI  - A two-photon fluorescence-correlation study of lectins interacting with
      carbohydrated 20 nm beads.
AB  - We present results of a two-photon fluorescence-correlation study carried out
      with glycosylated and untreated 20 nm fluorescing spheres that interacted with
      the carbohydrate-binding proteins soybean agglutinin (SBA) and concanavalin A
      (Con A). The assay principle allows protein-carbohydrate binding interactions to
      be determined without protein labeling. This assay might serve as a simple model
      system for studying physical and chemical interactions between proteins and
      carbohydrates, for example, at cell or virus surfaces. In experiments with
      galactosylated 20 nm beads and SBA, several stages of protein-carbohydrate
      interactions could be clearly distinguished. Initially, only a few lectins bound
      to the nanospheres. At higher lectin concentrations polymerization occurred, and
      aggregates consisting of about 2.6 x 10(5) glycosylated nanospheres were formed.
      At very high lectin concentrations, the degree of polymerization dropped, and the
      size of single SBA-covered nanospheres increased to approximately 40 nm. When Con
      A was used instead of SBA, a significantly smaller degree of aggregation (4 x
      10(4) spheres) was obtained. Treatment of unglycosylated 20 nm beads with SBA as
      a negative control sample resulted in a much lower unspecific aggregation (5 x
      10(3) spheres). The assay principle can thus help to elucidate relative binding
      affinities.

PMID- 16408310
TI  - Deciphering the biosynthesis pathway of the antitumor thiocoraline from a marine
      actinomycete and its expression in two streptomyces species.
AB  - Thiocoraline is a thiodepsipeptide antitumor compound produced by two
      actinomycetes Micromonospora sp. ACM2-092 and Micromonospora sp. ML1, isolated
      from two marine invertebrates (a soft coral and a mollusc) found of the Indian
      Ocean coast of Mozambique. By using oligoprimers derived from nonribosomal
      peptide synthetase (NRPS) consensus sequences, six PCR fragments containing
      putative NRPS adenylation domains were amplified from the chromosome of
      Micromonospora sp. ML1. Insertional inactivation of each adenylation domain
      showed that two of them generated nonproducing mutants, thereby indicating that
      these domains were involved in thiocoraline biosynthesis. Sequencing of a 64.6
      kbp DNA region revealed the presence of 36 complete open reading frames (ORFs)
      and two incomplete ones. Heterologous expression of a region of about 53 kbp,
      containing 26 of the ORFs, in Streptomyces albus and S. lividans led to the
      production of thiocoraline in these streptomycetes. Surprisingly, the identified
      gene cluster contains more NRPS modules than expected on the basis of the number
      of amino acids of thiocoraline. TioR and TioS would most probably constitute the
      NRPS involved in the biosynthesis of the thiocoraline backbone, according to the
      colinearity of the respective modules. It is proposed that two other NRPSs, TioY
      and TioZ, could be responsible for the biosynthesis of a small peptide molecule
      which could be involved in regulation of the biosynthesis of thicoraline in
      Micromonospora sp. ML1. In addition, a pathway is proposed for the biosynthesis
      of the unusual starter unit, 3-hydroxy-quinaldic acid.

PMID- 16408311
TI  - Improved cell viability of linear polyethylenimine through gamma-cyclodextrin
      inclusion for effective gene delivery.
AB  - A polypseudorotaxane consisting of a linear polyethylenimine with Mn of 22,000
      (LPEI22k) and gamma-cyclodextrins (gamma-CDs; LPEI22k/gamma-CD) has been examined
      as a gene carrier. The polyplex formation with luciferase-encoding plasmid DNA
      (pDNA), intracellular trafficking of polyplex, cytotoxicity, and transfection
      efficiency were evaluated by various characteristic methods. LPEI22k/gamma-CD
      formed a pDNA polyplex at higher N/P ratios than LPEI22k; this suggests that the
      gamma-CD threading sterically interfered with the polyplex formation. In
      addition, the zeta potentials of the polyplex significantly decreased due to the
      reduction in charge density of LPEI22k caused by gamma-CD threading. The cellular
      uptake of pDNA in the LPEI22k/gamma-CD polyplex was enhanced by free gamma-CDs
      released from the polyplex that might accelerate the cellular uptake through
      enhanced membrane affinity. LPEI22k/gamma-CD significantly increased cell
      viability even at high N/P ratios, and the polyplex showed high transfection
      efficacy. The low cytotoxicity and high gene expression of LPEI22k/gamma-CD are
      advantageous to polyplex administration in vivo.

PMID- 16408312
TI  - Aminoglycoside-quinacridine conjugates: towards recognition of the P6.1 element
      of telomerase RNA.
AB  - A modular synthesis has been developed which allows easy and rapid attachment of
      one or two aminoglycoside units to a quinacridine intercalator, thereby leading
      to monomeric and dimeric conjugates. Melting temperature (Tm) experiments show
      that the tobramycin dimeric conjugate TD1 exhibits strong binding to the P6.1
      element of human telomerase RNA. By contrast, tobramycin alone is much less
      efficient and the monomeric compound TM1 elicits a poor binding ability.
      Monitoring of the interaction by an electrophoretic mobility shift assay shows a
      1:1 stoichiometry for the binding of the dimeric compound to the hairpin
      structure and confirms the lower affinity for a control duplex. Protection
      experiments with RNase T1 indicate interaction of the drug both in the stem and
      in the loop of the hairpin. Taken together, the data suggest a binding of TD1
      inside the hairpin at the stem-loop junction. The same trends are observed with
      paromomycin and kanamycin analogues but with a lower affinity.

PMID- 16408313
TI  - Free-energy simulations and experiments reveal long-range electrostatic
      interactions and substrate-assisted specificity in an aminoacyl-tRNA synthetase.
AB  - Specific recognition of their cognate amino acid substrates by the aminoacyl-tRNA
      synthetase enzymes is essential for the correct translation of the genetic code.
      For aspartyl-tRNA synthetase (AspRS), electrostatic interactions are expected to
      play an important role, since its three substrates (aspartate, ATP, tRNA) are all
      electrically charged. We used molecular-dynamics free-energy simulations and
      experiments to compare the binding of the substrate Asp and its electrically
      neutral analogue Asn to AspRS. The preference for Asp is found to be very strong,
      with good agreement between simulations and experiment. The simulations reveal
      long-range interactions that electrostatically couple the amino acid ligand, ATP,
      and its associated Mg2+ cations, a histidine side chain (His448) next to the
      amino acid ligand and a flexible loop that closes over the active site in
      response to amino acid binding. Closing this loop brings a negatively charged
      glutamate into the active site; this causes His448 to recruit a labile proton,
      which interacts favorably with Asp and accounts for most of the Asp/Asn
      discrimination. Cobinding of the second substrate, ATP, increases specificity for
      Asp further and makes the system robust towards removal of His448, which is
      mutated to a neutral amino acid in many organisms. Thus, AspRS specificity is
      assisted by a labile proton and a cosubstrate, and ATP acts as a mobile
      discriminator for specific Asp binding to AspRS. In asparaginyl-tRNA synthetase,
      a close homologue of AspRS, a few binding-pocket differences modify the charge
      balance so that asparagine binding predominates.

PMID- 16408315
TI  - Structure and stereochemistry of products of hydroxylation of human steroid
      hormones by a housefly cytochrome P450 (CYP6A1).
AB  - The structure and stereochemistry of nine steroid metabolites isolated in
      quantities ranging from 0.15 to 1.8 mg were determined using a variety of NMR
      techniques, including heteronuclear multiple bond correlation (HMBC) using
      broadband adiabatic 13C pulses and phase-sensitive data presentation.
      Testosterone, androstenedione and progesterone were oxidized with housefly
      cytochrome P450 6A1 enzyme reconstituted in vitro with housefly NADPH cytochrome
      P450 reductase and cytochrome b5. NMR analysis in CD3OD using a modified HMBC
      sequence as well as 2D heteronuclear single quantum correlation (HSQC), COSY and
      nuclear Overhauser and exchange spectroscopy (NOESY), combined with a detailed
      analysis of J couplings showed that hydroxylation occurs exclusively on the beta
      face of the steroids, at positions 2, 12, and 15.

PMID- 16408316
TI  - Adiabatic JHSQC for 13C isotopomer analysis.
AB  - A previous implementation of JHSQC enhanced the detection limits for 13C
      isotopomer analysis, but owing to experimental instabilities required extensive
      calibration prior to data collection. The addition of adiabatic pulses as well as
      a double spin-echo during the heteronuclear transfer periods has dramatically
      increased the precision of the experiment and done away with the need for
      calibration prior to running each sample. This new experiment allows the
      sensitivity gains from inverse detection to be realized in a time-efficient
      manner for the experimentalist.

PMID- 16408314
TI  - Increased oxidation and degradation of cytosolic proteins in alcohol-exposed
      mouse liver and hepatoma cells.
AB  - We recently developed a sensitive method using biotin-N-maleimide (biotin-NM) as
      a probe to positively identify oxidized mitochondrial proteins. In this study,
      biotin-NM was used to identify oxidized cytosolic proteins in alcohol-fed mouse
      livers. Alcohol treatment for 6 wk elevated the levels of CYP2E1 and
      nitrotyrosine, a marker of oxidative stress. Markedly increased levels of
      oxidized proteins were detected in alcohol-fed mouse livers compared to pair-fed
      controls. The biotin-NM-labeled oxidized proteins from alcohol-exposed mouse
      livers were subsequently purified with streptavidin-agarose and resolved on 2-DE.
      More than 90 silver-stained protein spots that displayed differential intensities
      on 2-D gels were identified by MS. Peptide sequence analysis revealed that many
      enzymes or proteins involved in stress response, chaperone activity, intermediary
      metabolism, and antioxidant defense systems such as peroxiredoxin were oxidized
      after alcohol treatment. Smaller fragments of many proteins were repeatedly
      detected only in alcohol-fed mice, indicating that many oxidized proteins after
      alcohol exposure were degraded. Immunoblot results showed that the level of
      oxidized peroxiredoxin (inactivated) was markedly increased in the alcohol
      exposed mouse livers and ethanol-sensitive hepatoma cells compared to the
      corresponding controls. Our results may explain the underlying mechanism for
      cellular dysfunction and increased susceptibility to other toxic agents following
      alcohol-mediated oxidative stress.

PMID- 16408317
TI  - Enhancement of natural disease resistance in potatoes by chemicals.
AB  - The mechanism involved in systemic acquired resistance (SAR) can be non
      specifically induced in susceptible plants. In response to pathogens, plants'
      natural defence mechanisms include the production of lignin and phytoalexins and
      the induction of plant enzymes. The aim of this research was to study the
      induction of SAR mediated by the chemical activator DL-3-aminobutyric acid (BABA)
      and the fungicide fosetyl-aluminium in potato cultivars with different levels of
      resistance against Phytophthora infestans (Mont) de Bary. To study the chemical
      induction of the resistance, the foliage of several potato cultivars was sprayed
      with BABA, fosetyl-aluminium or water (as a control treatment). After 3 days the
      foliage was inoculated with P. infestans. Seven days after inoculation,
      development of disease symptoms in the foliage was assessed. In postharvest tuber
      samples, evidence for enhancement of the defence response was evaluated by
      measuring the protein content of several hydrolytic enzymes as well as the phenol
      and phytoalexin content. The highest level of protection against late blight was
      observed when the chemicals were applied at early stages of crop development. An
      increase in resistance to late blight was also detected in tubers after harvest.
      There was also an increase in the protein level of beta-1,3-glucanase and
      aspartic protease as well as in the phenol and phytoalexin content of potato
      tuber discs obtained from postharvest tubers of treated plants. Thus the
      protective effect seemed to persist throughout the whole crop cycle. This
      treatment may offer the possibility of controlling both foliage and tuber blight
      and could have a major impact in reducing over-winter survival of P. infestans in
      tubers.

PMID- 16408318
TI  - Spsgt1, a new essential gene of Schizosaccharomyces pombe, is involved in
      carbohydrate metabolism.
AB  - hSGT1 (human suppressor of Gcr two) was isolated as a suppressor gene of the gcr2
      mutation. Since Gcr2p is a key regulatory factor of glycolytic gene expression in
      Saccharomyces cerevisiae, hSGT1 is a candidate for a novel human transcription
      factor involved in carbohydrate metabolism. SGT1 appears to be conserved from
      Schizosaccharomyces pombe to human but not present in S. cerevisiae. To further
      study its function, we cloned the hSgt1p orthologue of Sz. pombe (Spsgt1) from
      Sz. pombe genomic DNA. Overall identity and similarity between SpSgt1p and hSgt1p
      are 24% and 37%, respectively. Disruption of Spsgt1 showed that Spsgt1 is
      essential for growth and, using a construct which conditionally expresses sgt1,
      which with low level expression growth was severely affected on glucose but
      normal on non-fermentable carbon sources. DNA microarray analyses showed that the
      transcription of many genes involved in carbohydrate metabolism and amino acid
      metabolism were upregulated in the mutant, suggesting that SpSgt1p may be
      involved in the regulation of carbohydrate metabolism. Furthermore, a GFP fusion
      of SpSgt1p was localized to the nucleus, fitting with the possibility of SpSgt1p
      as a transcription factor.

PMID- 16408319
TI  - A truncated derivative of nmt 1 promoter exhibits temperature-dependent induction
      of gene expression in Schizosaccharomyces pombe.
AB  - Despite increasing exploitation of Schizosaccharomyces pombe as a model system
      there is a lack of convenient vectors for research and application. Expression
      with the commonly used promoter, nmt 1, requires a laborious regime involving the
      removal of repressor, thiamine, from a growing culture and further growth for 18
      h to achieve maximum expression, thus underlining the need for more user-friendly
      promoters. We report here the isolation and characterization of a truncated
      derivative of the nmt 1 promoter having novel induction characteristics: it is
      induced by shift of growth temperature from 36 degrees C to 25 degrees C,
      achieving maximum expression within 3 h. Similar features of expression were
      observed with the reporter genes GFP and beta-galactosidase, a native gene, cdc
      18, and a commercially important foreign therapeutic protein, streptokinase. The
      new promoter element offers additional advantages, such as lack of deleterious
      effect on cell viability and potential ability to express toxic proteins. These
      features make the new promoter a potentially better alternative to nmt 1, both as
      a research tool and for expression of commercially important proteins in Sz.
      pombe, and suggest the possibility of using similar approaches to design
      promoters with novel and useful properties.

PMID- 16408320
TI  - Effect of Bacillus thuringiensis subsp. israelensis and neonicotinoid
      insecticides on the fungus gnat Bradysia sp nr. coprophila (Lintner) (Diptera:
      Sciaridae).
AB  - The soil bacterium Bacillus thuringiensis Berliner subsp. israelensis (Bti), the
      neonicotinoid insecticides dinotefuran, imidacloprid, thiamethoxam and
      clothianidin and the insect growth regulator pyriproxyfen were evaluated to
      determine their efficacy against the larval stages of the fungus gnat Bradysia sp
      nr. coprophila (Lintner) in the laboratory. Treatments were applied as a drench
      to the growing medium in polypropylene deli containers. The Bti treatments had no
      effect on either instar tested, whereas all the other compounds negatively
      affected both the second and third instars. This study demonstrates that the soil
      bacterium B. thuringiensis var. israelensis may not be active on these larval
      stages, whereas the neonicotinoid insecticides and the insect growth regulator
      pyriproxyfen are effective on these stages. The fact that Bti is not effective on
      the second and third instars of the fungus gnat means that greenhouse producers
      using this insecticide must make applications before fungus gnat populations
      build up and before overlapping generations develop.

PMID- 16408321
TI  - Enzymes of UDP-GlcNAc biosynthesis in yeast.
AB  - D-Glucosamine is an important building block of major structural components of
      the fungal cell wall, namely chitin, chitosan and mannoproteins. Other amino
      sugars, such as D-mannosamine and D-galactosamine, relatively abundant in higher
      eukaryotes, rarely occur in fungal cells and are actually absent from yeast and
      yeast-like fungi. The glucosamine-containing sugar nucleotide UDP-GlcNAc is
      synthesized in yeast cells in a four-step cytoplasmic pathway. This article
      provides a comprehensive overview of the present knowledge on the enzymes
      catalysing the particular steps of the pathway in Candida albicans and
      Saccharomyces cerevisiae, with a special emphasis put on mechanisms of the
      catalysed reactions, regulation of activity and perspectives for exploitation of
      enzymes participating in UDP-GlcNAc biosynthesis as potential targets for
      antifungal chemotherapy.

PMID- 16408322
TI  - Regeneration of sugarcane elite breeding lines and engineering of stem borer
      resistance.
AB  - Five elite sugarcane breeding lines were tested for efficiency in embryogenesis
      and plant regeneration. All of them produced regenerative embryogenic calli but
      with varied efficiencies. To engineer strongly insect-resistant sugarcanes, the
      GC content of a truncated cry1Ac gene, which encodes the active region of Cry1Ac
      insecticidal delta-endotoxin, was increased from the original 37.4 to 47.5%
      following the sugarcane codon usage pattern. The synthetic cry1Ac gene (s-cry1Ac)
      was placed under the control of maize ubiquitin promoter and introduced by
      microprojectile bombardment into the embryogenic calli of sugarcane lines YT79
      177 and ROC16. Southern blotting analysis showed that multicopies of s-cry1Ac
      were integrated into the genomes of transgenic sugarcane lines. Immunoblotting
      analysis identified 18 transgenic lines expressing detectable levels of s-Cry1Ac,
      which were estimated in the range of 1.8-10.0 ng mg(-1) total soluble proteins.
      Four transgenic and two parental lines were assayed for sugarcane stem borer
      resistance in leaf tissue feeding trials and greenhouse plant assays. The results
      showed that, while the untransformed control lines were severely damaged in both
      leaves and stems, the transgenic sugarcane lines expressing high levels of s
      Cry1Ac proteins were highly resistant to sugarcane stem borer attack, resulting
      in complete mortality of the inoculated insects within 1 week after inoculation.

PMID- 16408323
TI  - Fungicide control of mushroom cobweb disease caused by Cladobotryum strains with
      different benzimidazole resistance profiles.
AB  - The benzimidazole fungicides thiabendazole and carbendazim, and the imidazole
      fungicide prochloraz-Mn, were tested for their efficacy in controlling cobweb
      disease of mushrooms caused by two Cladobotryum isolates. Isolate 202A was
      benzimidazole-sensitive in vitro and cobweb growth on the casing was well
      controlled by both benzimidazole fungicides in cropping experiments. Carbendazim
      also controlled the development of spotting symptoms much more effectively than
      thiabendazole. A second isolate (192B1) was benzimidazole-resistant and was
      highly resistant to thiabendazole in vitro but it showed some sensitivity to
      carbendazim in vitro at moderate to high concentrations. Despite this,
      carbendazim did not control disease symptoms in cropping experiments, confirming
      that isolate 192B1 is cross-resistant to other benzimidazole fungicides. Both
      isolates showed some sensitivity to prochloraz-Mn in vitro. This fungicide gave
      between 45% and 65% control of cobweb growth on the casing caused by either 202A
      or 192B1 but gave no control of spotting symptoms. Reducing the fungicide
      application volume did not give enhanced disease control. The emergence of
      benzimidazole resistance reduces the value of benzimidazoles in the control of
      mushroom pathogens. However, the lack of effective alternatives means they
      continue to have utility in cases where pathogens are still sensitive but this
      requires regular monitoring of pathogen populations for resistance.

PMID- 16408324
TI  - Stimulation of the rat somatosensory cortex at different frequencies and pulse
      widths.
AB  - Functional MRI (fMRI) during electrical somatosensory stimulation of the rat
      forepaw is a widely used model to investigate the functional organization of the
      somatosensory cortex or to study the underlying mechanisms of the blood oxygen
      level-dependent (BOLD) response. In reality, somatosensory stimuli have complex
      timing relationships and are of long duration. However, by default electrical
      sensory stimulation seems to be performed at an extremely short pulse width (0.3
      ms). As the pulse duration may alter the neuronal response, our aim was to
      investigate the influence of a much longer stimulus pulse width (10 ms) using
      BOLD fMRI during electrical forepaw stimulation. The optimal neuronal response
      was investigated by varying the stimulus frequency at a fixed pulse duration (10
      ms) and amplitude (1 mA). In a parallel experiment we measured the neuronal
      response directly by recording the somatosensory evoked potentials (SEPs).
      Quantification of the BOLD data revealed a shift in the optimal response
      frequencies to 8-10 Hz compared with 1 Hz at 0.3 ms. The amplitude of the
      recorded SEPs decreased with increasing stimulation frequency and did not display
      any correlation with the BOLD data. Nevertheless, the summated SEPs, which are a
      measure of the integrated neuronal activity as a function of time, displayed a
      similar response profile, with a similar maximum as observed by relative BOLD
      changes. This shift in optimal excitation frequencies might be related to the
      fact that an increased pulse width of an electrical stimulus alters the nature of
      the stimulation, generating also sensorimotor instead of merely somatosensory
      input. This may influence or alter the activated pathways, resulting in a shift
      in the optimal response profile.

PMID- 16408325
TI  - Monitoring of EAE onset and progression in the common marmoset monkey by
      sequential high-resolution 3D MRI.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced by myelin-oligodendrocyte
      glycoprotein (MOG) in common marmosets (Callithrix jacchus) is a model for
      multiple sclerosis. Here, EAE was induced in four common marmosets by 250-300
      microg recombinant rat MOG. In addition to a detailed disability scoring, T2- and
      T1-weighted high-resolution 3D MRI was performed to assess the onset and
      development of cerebral lesions. The findings were confirmed by histopathology in
      all animals. Although the animals exhibited a large heterogeneity with regard to
      onset and localization of lesions and also to disease duration and severity of
      disability signs, none of the animals revealed any evidence of recovery. A
      specification of the disability scoring system to account for different aspects
      of the disease led to a good concurrence of the first MRI-detectable lesion and
      the onset of central nervous system (CNS) symptoms. The results suggest that MRI
      monitoring of white matter lesions in conjunction with disability scores that
      focus on CNS symptoms may be a suitable method to evaluate novel therapeutic
      interventions even in the presence of pronounced interindividual heterogeneity.

PMID- 16408326
TI  - Cryoablation proves effective, safe, durable treatment for prostate cancer.

PMID- 16408327
TI  - MRI better than FDG-PET at detecting liver tumors.

PMID- 16408328
TI  - Bacteria not welcome at the MRC?

PMID- 16408329
TI  - The neurologist as expert witness.

PMID- 16408330
TI  - Self-help websites.

PMID- 16408331
TI  - The efficacy of a nerve stimulator (Cavermap) to enhance autonomic nerve
      identification and confirm nerve preservation during total mesorectal excision.
AB  - PURPOSE: Sexual dysfunction after total mesorectal excision may be caused by
      injury to the autonomic nerves. During surgery, nerve identification is not
      always achieved, and, to date, there has been no method to objectively confirm
      nerve preservation. The aim of this study was to assess the efficacy of a nerve
      stimulating device (CaverMap) to assist in the intraoperative identification of
      the autonomic nerves during total mesorectal excision, and objectively confirm
      nerve preservation after proctectomy is completed. PATIENTS AND METHODS: Sexually
      active consecutive male patients undergoing total mesorectal excision were
      prospectively enrolled in this study. During pelvic dissection, the surgeon
      attempted to localize the hypogastric and cavernous nerves. CaverMap was used to
      confirm these findings and to facilitate the identification in cases of
      uncertainty. At the completion of proctectomy, the nerves were restimulated to
      ensure preservation. Factors that could affect the surgeon's ability to localize
      the nerves and CaverMap to confirm this were evaluated. RESULTS: Twenty-nine male
      patients with a median age of 58 years were enrolled in this study. An attempt to
      visualize the hypogastric nerves during dissection was made in 26 patients; the
      surgeon was able to identify the nerves in 19 (73 percent) patients. CaverMap
      successfully identified the nerves in six of the seven remaining patients, and
      failed to identify them in only one case. An attempt to localize the cavernous
      nerves during dissection was made in 13 patients, of which localization was
      successful in 8 (61.5 percent) patients. CaverMap improved the identification
      rate in four of the remaining five patients. After proctectomy, CaverMap
      successfully confirmed the preservation of both hypogastric and cavernous nerves
      in 27 of 29 (93 percent) patients. A history of previous surgery statistically
      correlated with failure to identify the hypogastric nerves by the surgeon (P =
      0.005). There were no adverse events related to use of the device. CONCLUSION:
      CaverMap may be a useful tool to facilitate identification of the pelvic
      autonomic nerves during total mesorectal excision and to objectively confirm
      nerve preservation.

PMID- 16408332
TI  - Report highlights European inequalities in access to cancer drugs.

PMID- 16408333
TI  - Championing a forgotten tribe.

PMID- 16408334
TI  - 7th Framework: funding hopes dashed.

PMID- 16408335
TI  - [Melatonin in the environmental medicine diagnosis in connection with
      electromagnetic fields: statement of the commission "Methods and Quality
      Assurance in Environmental Medicine" ].

PMID- 16408336
TI  - [Guidelines of the environmental protection agency for the modified/changed
      implementation of the KTW-examination of the validity of the European acceptance
      system for building materials in contact with drinking water (EAS): standard:
      18.11.2005].

PMID- 16408337
TI  - [Therapeutic exercise in the prevention of the secondary hip dislocation in
      Little disease].

PMID- 16408338
TI  - Obsessive-compulsive disorder: Part II. Treating the symptoms and studying the
      brain.

PMID- 16408339
TI  - The prevalence and treatment of mental illness today.

PMID- 16408340
TI  - Is the rate of autism rising?

PMID- 16408341
TI  - DHEA for depression.

PMID- 16408342
TI  - Questions & answers. What is Type D personality?

PMID- 16408343
TI  - Ovarian cancer. Be aware of warning signs.

PMID- 16408344
TI  - Health tips. Preventing blood clots while traveling.

PMID- 16408345
TI  - Whooping cough vaccine approved for adults.

PMID- 16408346
TI  - Erythropoietin. Treating severe anemia.

PMID- 16408347
TI  - Adult acne. Troublesome, but treatable.

PMID- 16408348
TI  - How can I know whether my back pain may be due to cancer or some other serious
      cause, rather than just a typical backache?

PMID- 16408349
TI  - Digital mammography better for some women. New technology helps see through
      breast tissue that can hide cancers.

PMID- 16408350
TI  - Exercises for aching hands. Putting hands through their paces can help relieve
      pain and prevent injury.

PMID- 16408351
TI  - The lowdown on thyroid slowdown. Hypothyroidism can cause a host of health
      problems. Fortunately, the condition can be easily diagnosed and treated.

PMID- 16408352
TI  - New trial to test hormone therapy in younger women.

PMID- 16408353
TI  - By the way, doctor. For two years in a row, the lab that handles my Pap smears
      has reported "insufficient cell count". My doctor says it's nothing to worry
      about, but my health insurance company considers these "abnormal" Paps and has
      put me in a higher-risk category because of it. Should I be concerned?

PMID- 16408354
TI  - Ensulizole (phenylbenzimidazole-5-sulfonic acid) as a cause of facial dermatitis:
      two cases.

PMID- 16408355
TI  - Contact dermatitis from Frontline Top Spot.

PMID- 16408356
TI  - Lack of efficacy of a combination sunblock and "jellyfish sting inhibitor"
      topical preparation against Physalia sting.

PMID- 16408358
TI  - Corporate influence on chemical exposure levels.

PMID- 16408357
TI  - A topical cream containing a zinc gel (Allergy Guard) as a prophylactic against
      latex glove-related contact dermatitis.

PMID- 16408359
TI  - Breastfeeding: nature's MRE.

PMID- 16408360
TI  - COEPs contribute to Hurricane relief.

PMID- 16408361
TI  - Assessment of aseptic loosening of the acetabular component in a total hip
      replacement with 99mTc-DPD-SPECT/spiral-CT hybrid imaging.

PMID- 16408363
TI  - NME digest.

PMID- 16408362
TI  - [Therapy-determined positron emission tomography in metastatic rectal carcinoma].

PMID- 16408364
TI  - Heubner's artery.

PMID- 16408365
TI  - The law of specific nerve energies and sensory sport.

PMID- 16408366
TI  - (Neurogenic) Claudication.

PMID- 16408367
TI  - The UICC My Child Matters initiative awards: combating cancer in children in the
      developing world.

PMID- 16408368
TI  - Bevacizumab and erlotinib show promise for kidney cancer.

PMID- 16408369
TI  - Killing regulatory immune cells boosts effects of cancer vaccine.

PMID- 16408370
TI  - Aspirin use reduces skin-cancer risk.

PMID- 16408371
TI  - MRI tracks cancer-vaccine cells.

PMID- 16408372
TI  - Tyrosine kinase ACK1 promotes prostate tumorigenesis.

PMID- 16408373
TI  - Testing times for ovarian cancer.

PMID- 16408374
TI  - New Italian website for patients with cancer.

PMID- 16408375
TI  - Genetic deletions help determine neuroblastoma prognosis.

PMID- 16408376
TI  - High-dose chemotherapy for advanced breast cancer.

PMID- 16408377
TI  - Radiation sensitiser effective against liver disease.

PMID- 16408378
TI  - Trastuzumab for early breast cancer: evolution or revolution?

PMID- 16408379
TI  - Piso's madness (CIC. IN PIS. 21 and 47).

PMID- 16408381
TI  - Conversation with Sheila Blume.

PMID- 16408380
TI  - [Recurrent cancer of the middle part of the larynx after radiotherapy: a
      fibroendoscopic approach].

PMID- 16408382
TI  - [Safety of pegylated interferon in patients with hepatitis C virus induced
      cirrhosis].
AB  - OBJECTIVES: The authors described their experience with the therapy with
      pegylated interferon and its safety in patients with hepatitis C virus (HCV)
      induced liver cirrhosis treated at First Department of Medicine, Medical School,
      University of Pecs and at Tawam Hospital, Al Ain, United Arab Emirates. PATIENTS
      AND METHODS: Twenty four (12 male, 12 female, average: 55.66 +/- 7. 02 years)
      anti-HCV and/or HCV-RNA PCR positive cirrhotic patients were examined. Liver
      cirrhosis was diagnosed by abdominal ultrasound and/or histological examination
      of liver biopsy. RESULTS: Different genotypes of HCV were detected: genotype 1 in
      7 cases, genotype 2 in 1 person, genotype 3 in 3 cases. Genotype 4 was detected
      in 10 patients, all of them were treated out of Hungary. Thirteen of 24 patients
      were not treated earlier, 6 persons were non-responders to previous interferon
      monotherapy, pegylated interferon was administered to 5 patients because of
      relapse. Biochemical parameters showed improvement in 16 cases (16/24, 66.66%),
      but did not in 5 patients. Until now, virological response was achieved in 13
      patients (13/24, 54.16%), while three patients remained HCV-PCR positive.
      Temporary dose reduction was needed in 13/24 cases (54.16%). Withdrawal of
      therapy became necessary in only 2 patients due to severe neutropenia,
      thrombocytopenia and/or signs of decompensation. CONCLUSIONS: Pegylated
      interferon treatment is well tolerated by patients with compensated liver
      cirrhosis (Child-Pough stage A). Frequent side-effects (half of all cases) were
      usually mild or moderate requiring discontinuation only in 2 of 24 patients. The
      incidence of neutropenia and thrombocytopenia emphasizes the need of frequent
      blood cell count tests and patients follow up.

PMID- 16408383
TI  - [Interstitial lung disease in mixed connective tissue disease].
AB  - INTRODUCTION: The authors analyzed the incidence of interstitial lung disease in
      mixed connective tissue disease. They were seeking an answer to the following
      problems: the nature of the pathological course of mixed connective tissue
      disease complicated by and the therapy to be used in interstitial lung disease.
      PATIENTS AND METHODS: 179 patients were followed up during a period of 15.9 +/-
      6.1 years. Interstitial lung disease was diagnosed using high resolution computed
      tomography. The diagnosis of interstitial lung disease was not obvious in 5
      patients thus open lung biopsy was performed, which confirmed common interstitial
      pneumonitis. The patients were followed-up, and the data of computed tomography
      and respiratory function tests were detected 6 months, and then 4 years after the
      acute lung disease complicated by mixed connective tissue disease. RESULTS: Out
      of the 179 mixed connective tissue disease patients 96 (53.6%) had interstitial
      lung disease. The onset of interstitial lung disease was the most frequent in the
      2-4 years of the disease. Four years after the first appearance of interstitial
      lung disease severe fibrosis was diagnosed in 24 patients (25%). A honey comb
      formation in the lung developed only in one patient. For the treatment of
      interstitial lung disease, corticosteroid treatment had to be combined with
      cyclophosphamide in 51 cases. In 4 patients (24%), pulmonary arterial
      hypertension evolved 2-4 years following interstitial lung disease. The high
      pulmonary arterial pressure decreased using pulsed corticosteroid treatment,
      cyclophosphamide, prostacyclin analogue, anticoagulants therapy and the 4
      patients stay alive. The pulmonary arterial hypertension was caused by
      obliterative vasculopathy. CONCLUSION: Pulmonary involvement is found in more
      than half of the patients with mixed connective tissue disease. Early diagnosis
      of interstitial lung disease is possible by computed tomography. Interstitial
      lung disease can be treated by the combination of corticosteroids and
      cyclophosphamide. The authors were the first to detect the coexistence of
      interstitial lung disease and pulmonary arterial hypertension in mixed connective
      tissue disease. Subsequent respiratory alterations in these patient necessitate
      regular patient follow up.

PMID- 16408384
TI  - [Randomised placebo controlled double blind study on the effect of prebiotic
      oligosaccharides on intestinal flora in healthy infants].
AB  - AIM: Effects of supplementing prebiotic oligosaccharides to formula for healthy
      infants were studied in this placebo controlled, randomised, double blind study.
      METHODS: Ninety-seven infants were included into the study; among them 42 breast
      fed infants, 14 infants fed formula supplemented with 0.4 g/100ml
      oligosaccharides (9 to 1 mixture of galacto- and fructooligosaccharides) and 13
      infants fed control formula were followed-up throughout the 12-week-long study
      period. The groups receiving formula were compared with statistical methods,
      whereas data of breast-fed infants served as reference values. RESULTS: Infants
      fed the two formulae did not differ in nutrient intakes, growth, occurrence rate
      of feeding difficulties and atopic manifestations, or in calcium excretion. The
      intestinal flora did not differ between the two formula fed groups at the
      beginning of the study. In contrast, numbers of Bifidobacteriae were
      significantly higher in infants receiving the formula supplemented with prebiotic
      oligosaccharides both at the 14th day (9 x 1011 versus 5 x 1010, colony forming
      units/g faeces, median, p < 0.05) and 28th day (9 x 1012 versus 5 x 1010, p <
      0.05) of the study. CONCLUSION: In this study, supplementation of infant formula
      with prebiotic oligosaccharides resulted in ameliorating the difference in
      intestinal flora between formula fed and breast-fed healthy infants.

PMID- 16408385
TI  - [Contrast medium induced nephropathy].
AB  - Contrast medium induced nephropathy. The wide-spread use of invasive diagnostic
      and therapeutic procedures makes the use of contrast media more common. Acute
      renal failure may develop following their intravascular administration, referred
      as contrast medium induced nephropathy or briefly contrast nephropathy. It
      develops especially in patients with diabetic nephropathy, in cases of volume
      depletion and in chronic renal insufficiency. Contrast nephropathy is the third
      most common cause of acute renal failure acquired in hospital. In their present
      work current literature, pathogenesis, clinical characteristics and potential
      ways of prevention are reviewed.

PMID- 16408386
TI  - [Treatment of male fertility disorders].

PMID- 16408387
TI  - [History of the Hungarian hepatology from the beginnings to the end of the 2nd
      World War].

PMID- 16408388
TI  - [Stahl on disease of courtiers].

PMID- 16408389
TI  - [Post-traumatic stress syndrome is a public disease. Treatment of the traumatized
      must be integrated in health care services].

PMID- 16408390
TI  - [Specialists teams for trauma-related disorders--in short supply in Sweden. There
      is a lack of both resources and effective therapeutic methods, a survey shows].
AB  - Psychological effects of serious traumas can cause severe personal suffering for
      the individual and will also mean a great economical loss for the individual and
      for the society in terms of decreased functioning due to illness. The Swedish
      National Center for Disaster Psychiatry has done a survey to investigate the
      public resources for acute psychosocial support and for treatment of disorders
      after psychological traumas. The organization of psychosocial support within the
      public health care system after major disasters is functioning all over Sweden.
      Twenty-seven clinics were identified. A majority of these clinics have
      specialized in the support and treatment of victims of war and torture. Fifty
      percent of the public medical service areas do not have specialist clinics for
      treatment of trauma related disorders. At many places there is a lack of
      specialist treatment resources for people who have developed disorders after
      experiences of assaults, serious accidents or other types of life threats or
      sudden loss. There is an obvious need of increased resources in this area.

PMID- 16408391
TI  - [Mycoplasma genitalium should be suspected in unspecific urethritis and
      cervicitis. A study from Vasterbotten confirms the high prevalence of the
      bacteria].
AB  - The microbe Mycoplasma genitalium has in several studies been proposed as an
      individual cause of non-gonococcal urethritis (NGU) in men, and has been
      associated with pelvic inflammatory disease (PID) and salpingitis. The prevalence
      of M genitalium has generally been 50-90% of the prevalence of C trachomatis, and
      this seems to be the case in Sweden as well. This is the first study of the
      pathogenesis and prevalence of M genitalium in northern Sweden. In total 823
      samples, 340 from women and 483 from men, were screened for M genitalium by using
      a PCR method. Thirtythree (4.0%) patients, 13 (3.8%) women and 20 (4.1%) men,
      were infected by M genitalium. In the same group 60 (7.3%) patients, 16 (4.7%)
      women and 44 (9.1%) men, were infected by Chlamydia trachomatis. None of the 22
      patients that were tested after treatment with azitromycin was still infected.

PMID- 16408393
TI  - [Can chronic pain and spreading of pain be induced via glial mechanisms? New
      hypotheses on the generators maintaining protracted pain conditions].
AB  - There are various types of pain: acute, inflammatory, and neuropathic. The latter
      starts with a nerve injury, which could be secondary to an inflammatory reaction.
      Neuropathic pain often remains even after the original injury has healed and
      sometimes becomes chronic. It has recently been proposed that activated
      astrocytes and microglial cells could be the generators maintaining neuropathic
      pain. As astrocytes exhibit gap junction coupled networks, glia may be involved
      in spreading of pain sensations in form of Ca2+ oscillations or waves. Astrocytic
      Ca2+ oscillations induce ATP release which in turn stimulates both microglial
      cells and those monocytes that have crossed the blood-brain barrier, and also
      stimulates distant astrocyte networks and microglial cells. These activated cells
      release pro-inflammatory cytokines. One theory is that the Ca2+ oscillations by
      their induction and release of growth factors, give rise to new synapses, thereby
      establishing new neuronal contacts for maintaining and spreading pain sensation.

PMID- 16408392
TI  - [Conformationally altered proteins cause neurodegenerative diseases].
AB  - Brain aggregates of conformationally altered proteins are key features of
      neurodegeneration and are believed to directly cause or contribute to disease
      development. Mechanisms underlying the dysregulation of proteins in Alzheimer's
      disease, Parkinson's disease, amyotrophic lateral sclerosis and other
      neurodegenerative disorders are now being characterized, due to the discovery of
      genes causing rare disease forms. As of today, only symptomatic pharmacotherapies
      are available, but new insights into the underlying molecular mechanisms are
      providing strategies to prevent or even cure these devastating disorders.

PMID- 16408394
TI  - [Treatment of anxiety syndrome. A systematic literature review. Summary and
      conclusions by the SBU].
AB  - A report by the Swedish Council on Technology Assessment in Health Care (SBU) has
      reviewed, classified and evaluated the scientific literature on treatment of
      panic syndrome, specific phobias, social phobia, obsessive-compulsive syndrome
      (OCD), generalized anxiety syndrome (GAD) and post-traumatic stress disorder
      (PTSD). The review included treatment of children, adolescents and adults. The
      report concludes that there is effective treatment available for all anxiety
      syndromes. However in general, the effect is often moderate and symptoms reappear
      when the treatment period is discontinued. For adults, scientific evidence
      supports the use of paroxetine and sertraline for all syndromes except specific
      phobias. For the other SSRI's there is also evidence for the use of fluoxetin in
      OCD and PTSD, for fluvoxamine in social phobia and OCD and for escitalopram in
      social phobia. Other antidepressant drugs with a strong scientific support is
      venlafaxin in social phobia and GAD, imipramin in panic syndrome and
      chlomipramine in panic syndrome and OCD. Among psychological treatments, there is
      scientific evidence for cognitive behavior therapy (CBT) for treatment of panic
      syndrome, specific phobias, social phobia, PTSD and GAD. Exposure, with or
      without other psychotherapeutic interventions, has scientific support for
      efficacy in panic disorder (both in terms of number of panic attacks and for
      agoraphobia), specific phobias, OCD and PTSD. Use of eye movement desensitization
      and reprocessing (EMDR) has scientific support for treatment of PTSD.

PMID- 16408395
TI  - [Spy fiction author scrutinizes drug industry].

PMID- 16408396
TI  - [The difficult drug prescription. The HSL compliance guide. The ABLA's seed must
      not blow away!].

PMID- 16408397
TI  - [Hypertension trials--for whom?].

PMID- 16408398
TI  - [A general practitioner's holistic view doesn't exclude specialist support!].

PMID- 16408400
TI  - [A cybervision--what if...].

PMID- 16408399
TI  - [A new list of doping preparations starting January 1, 2006--cortisone for local
      administration is no longer included!].

PMID- 16408401
TI  - [Gained experience at the expense of sleep].

PMID- 16408402
TI  - [Health of the elderly--a halting comparison between 1992 and 2002].

PMID- 16408403
TI  - Doctors in society. Medical professionalism in a changing world.
AB  - Medicine bridges the gap between science and society. Indeed, the application of
      scientific knowledge to human health is a crucial aspect of clinical practice.
      Doctors are one important agent through which that scientific understanding is
      expressed. But medicine is more than the sum of our knowledge about disease.
      Medicine concerns the experiences, feelings, and interpretations of human beings
      in often extraordinary moments of fear, anxiety, and doubt. In this extremely
      vulnerable position, it is medical professionalism that underpins the trust the
      public has in doctors. This Working Party was established to define the nature
      and role of medical professionalism in modern society. Britain's health system is
      undergoing enormous change. The entry of multiple health providers, the wish for
      more equal engagement between patients and professionals, and the ever-greater
      contribution of science to advances in clinical practice all demand a clear
      statement of medicine's unifying purpose and doctors' common values. What is
      medical professionalism and does it matter to patients? Although evidence is
      lacking that more robust professionalism will inevitably lead to better health
      outcomes, patients certainly understand the meaning of poor professionalism and
      associate it with poor medical care. The public is well aware that an absence of
      professionalism is harmful to their interests. The Working Party's view, based on
      the evidence it has received, is that medical professionalism lies at the heart
      of being a good doctor. The values that doctors embrace set a standard for what
      patients expect from their medical practitioners. The practice of medicine is
      distinguished by the need for judgement in the face of uncertainty. Doctors take
      responsibility for these judgements and their consequences. A doctor's up-to-date
      knowledge and skill provide the explicit scientific and often tacit experiential
      basis for such judgements. But because so much of medicine's unpredictability
      calls for wisdom as well as technical ability, doctors are vulnerable to the
      charge that their decisions are neither transparent nor accountable. In an age
      where deference is dead and league tables are the norm, doctors must be clearer
      about what they do, and how and why they do it. We define medical professionalism
      as a set of values, behaviours, and relationships that underpin the trust the
      public has in doctors. We go on to describe what those values, behaviours, and
      relationships are, how they are changing, and why they matter. This is the core
      of our work. We have also identified six themes where our definition has further
      implications: leadership, teams, education, appraisal, careers, and research. The
      Working Party's definition and description of medical professionalism, and the
      recommendations arising from them, can be found in Section 5 of this report. If
      our recommendations are acted upon, we believe that professionalism could
      flourish and prosper to the benefit of patients and doctors alike. However, the
      exercise of medical professionalism is hampered by the political and cultural
      environment of health, which many doctors consider disabling. The conditions of
      medical practice are critical determinants for the future of professionalism. We
      argue that doctors have a responsibility to act according to the values we set
      out in this report. Equally, other members of the healthcare team--notably
      managers--have a reciprocal duty to help create an organisational infrastructure
      to support doctors in the exercise of their professional responsibilities. Just
      as the patient-doctor partnership is a pivotal therapeutic relationship in
      medicine, so the interaction between doctor and manager is central to the
      delivery of professional care. High-quality care depends on both effective health
      teams and efficient health organisations. Professionalism therefore implies
      multiple commitments--to the patient, to fellow professionals, and to the
      institution or system within which healthcare is provided, to the extent that the
      system supports patients collectively. A doctor's corporate responsibility,
      shared as it is with managers and others, is a frequently neglected aspect of
      modern practice. The audience for this report is, first and foremost, doctors.
      But we believe it should be of equal interest to patients, policy-makers, members
      of other health professions, and the media. All these groups have a vital part to
      play in discussing and advancing medical professionalism. This report is only the
      beginning of an effort by the Royal College of Physicians, together with others,
      to initiate a public dialogue about the role of the doctor in creating a
      healthier and fairer society. Medical professionalism has roots in almost every
      aspect of modern healthcare. This Working Party could not hope to solve all the
      issues and conflicts surrounding professionalism in practice today. But our
      collective and abiding wish is to put medical professionalism back onto the
      political map of health in the UK.

PMID- 16408404
TI  - Pulmonary physicians in the practice of sleep medicine.

PMID- 16408405
TI  - Sleep, learning, and the developing brain: early-to-bed as a healthy and wise
      choice for school aged children.

PMID- 16408406
TI  - Hyperarousal as the basis for insomnia: effect size and significance.

PMID- 16408407
TI  - The China syndrome: sleep in the elderly--a world-wide problem.

PMID- 16408408
TI  - Too little sleep gradually desensitizes the serotonin 1A receptor system.
AB  - STUDY OBJECTIVES: In our 24-hour society, frequently disrupted and restricted
      sleep is a rapidly increasing problem that may contribute to the development of
      diseases such as depression. One of the proposed neurobiological mechanisms
      underlying depression is a disturbance in the brain's serotonergic
      neurotransmission, particularly a desensitization of the serotonin (5-HT)1A
      receptor system. However, a relationship between chronic sleep loss and changes
      in (5-HT)1A receptors has not been established yet. Therefore, in the present
      study, we experimentally tested the hypothesis that chronic sleep restriction
      leads to desensitization of the (5-HT)1A receptor system. DESIGN: Rats were
      subjected to a schedule of restricted sleep allowing them 4 hours of sleep per
      day. Sleep restriction was achieved by placing the animals in slowly rotating
      wheels. The sensitivity of the (5-HT)1A receptor system was examined by measuring
      the hypothermic response to a standard injection of a 1A agonist. RESULTS: After
      2 days of restricted sleep, the sensitivity of the (5-HT)1A receptor system was
      not yet affected; however, after 8 days of sleep restriction, it was
      desensitized. Control experiments indicated that the effect of sleep restriction
      was not due to forced activity or stress. Importantly, the desensitization of the
      (5-HT)1A system persisted for many days even with unlimited recovery sleep.
      Normalization occurred gradually but required at least 7 days. CONCLUSIONS:
      Chronic sleep restriction causes a gradual and persistent desensitization of the
      (5-HT)1A receptor system. This finding provides a link between chronic sleep loss
      and sensitivity for disorders that are associated with altered serotonergic
      neurotransmission.

PMID- 16408409
TI  - Fatigue, sleepiness, and performance in simulated versus real driving conditions.
AB  - STUDY OBJECTIVES: To determine whether real-life driving would produce different
      effects from those obtained in a driving simulator on fatigue, performances and
      sleepiness. DESIGN: Cross-over study involving real driving (1200 km) or
      simulated driving after controlled habitual sleep (8 hours) or restricted sleep
      (2 hours). SETTING: Sleep laboratory and open French Highway. PARTICIPANTS:
      Twelve healthy men (mean age +/- SD = 21.1 +/- 1.6 years, range 19-24 years, mean
      yearly driving distance +/- SD = 6563 +/- 1950 miles) free of sleep disorders.
      MEASUREMENTS: Self-rated fatigue and sleepiness, simple reaction time before and
      after each session, number of inappropriate line crossings from the driving
      simulator and from video-recordings of real driving. RESULTS: Line crossings were
      more frequent in the driving simulator than in real driving (P < .001) and were
      increased by sleep deprivation in both conditions. Reaction times (10% slowest)
      were slower during simulated driving (P = .004) and sleep deprivation (P = .004).
      Subjects had higher sleepiness scores in the driving simulator (P = .016) and in
      the sleep restricted condition (P = .001). Fatigue increased over time (P = .011)
      and with sleep deprivation (P = .000) but was similar in both driving conditions.
      CONCLUSIONS: Fatigue can be equally studied in real and simulated environments
      but reaction time and self-evaluation of sleepiness are more affected in a
      simulated environment. Real driving and driving simulators are comparable for
      measuring line crossings but the effects are of higher amplitude in the simulated
      condition. Driving simulator may need to be calibrated against real driving in
      various condition.

PMID- 16408411
TI  - Sex differences in delta and alpha EEG activities in healthy older adults.
AB  - STUDY OBJECTIVES: To examine sex effects on sleep stages and electroencephalogram
      (EEG) spectral power in older adults. DESIGN: Sleep was polygraphically recorded
      for 2 consecutive nights, and blood was sampled during the last 24 hours.
      SETTING: The University of Chicago Clinical Research Center. PARTICIPANTS: Two
      groups of healthy nonobese older subjects: 10 men (59 +/- 2 years), and 10
      postmenopausal women (63 +/- 2 years). INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: A spectral analysis of the EEG was performed in the delta and alpha
      bands. There were no sex differences in sleep stages. Blood sampling resulted in
      reductions of total sleep time, sleep maintenance, slow-wave sleep, and absolute
      delta activity that were all larger in women than in men. In absolute values,
      delta and alpha activities in non-rapid eye movement (NREM) and rapid eye
      movement (REM) sleep were higher in women than in men, but, for delta activity,
      the sex differences were larger in REM than in NREM sleep. In women, but not in
      men, absolute delta activity in REM was decreased during blood sampling and was
      strongly correlated with absolute delta activity in NREM. Delta activity in REM
      did not dissipate across the night in either group. When normalized for the
      activity in REM sleep, the sex difference in delta activity in NREM sleep was
      reversed, with lower activity in women. CONCLUSIONS: Sex differences in sleep EEG
      variables are present in older adults. When normalized, delta activity in older
      women is lower than in older men, which may be more consistent with sex
      differences in subjective complaints, in fragility of sleep in the presence of
      environmental disturbances, and in the relationship to growth-hormone release.

PMID- 16408410
TI  - Sex differences in nocturnal growth hormone and prolactin secretion in healthy
      older adults: relationships with sleep EEG variables.
AB  - STUDY OBJECTIVES: To examine sex differences in nocturnal growth hormone and
      prolactin release in older adults. DESIGN: Sleep was polygraphically recorded for
      2 consecutive nights, and blood was sampled at frequent intervals during the last
      24 hours. SETTING: The University of Chicago Clinical Research Center.
      PARTICIPANTS: Two groups of healthy nonobese older subjects: 10 men (59 +/- 2
      years, mean +/- SEM), and 10 postmenopausal women (63 +/- 2 years).
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A spectral analysis of the
      electroencephalogram was performed in the delta and alpha bands. When delta
      activity was normalized for the activity in rapid eye movement sleep, women had
      lower delta activity than men. Growth hormone secretion was estimated by
      deconvolution. The prolactin profile was quantified by a best-fit curve. In both
      sexes, growth hormone was released both before and after sleep onset. In men,
      there was no relationship between presleep growth hormone release and subsequent
      sleep quality and postsleep growth hormone release correlated with delta
      activity. In women, presleep growth hormone release appeared to inhibit both
      postsleep growth hormone release and sleep consolidation. Prolactin release was
      related to rapid eye movement sleep and was lower in men than in women. Women
      with poor sleep maintenance had a lower prolactin acrophase. CONCLUSIONS: Major
      sex differences in the nocturnal profiles of growth hormone and prolactin and
      their relationship to sleep electroencephalogram variables are present in healthy
      older adults. Our analyses suggest that lower sleep-onset release of growth
      hormone in women as compared with men could be related to lower levels of delta
      activity. Improvements in the homeostatic control of sleep could have hormonal
      benefits in older adults.

PMID- 16408413
TI  - Association between atrial fibrillation and central sleep apnea.
AB  - BACKGROUND: We previously described an association between atrial fibrillation
      and central sleep apnea in a group of patients with congestive heart failure. We
      hypothesized that the prevalence of atrial fibrillation might also be increased
      in patients with central sleep apnea in the absence of other cardiac disease.
      METHODS AND RESULTS: We compared the prevalence of atrial fibrillation in a
      series of 60 consecutive patients with idiopathic central sleep apnea (apnea
      hypopnea index > 10 events per hour, > 50% central events) with that in 60
      patients with obstructive sleep apnea (apnea-hypopnea index > 10, > 50%
      obstructive events) and 60 patients without sleep apnea (apnea-hypopnea index <
      10), matched for age, sex, and body mass index. Subjects with a history of
      congestive heart failure, coronary artery disease, or stroke were excluded from
      the study. The prevalence of atrial fibrillation among patients with idiopathic
      central sleep apnea was found to be significantly higher than the prevalence
      among patients with obstructive sleep apnea or no sleep apnea (27%, 1.7%, and
      3.3%, respectively, P < .001). However, hypertension was most common and oxygen
      desaturation most extreme among patients with obstructive sleep apnea.
      CONCLUSIONS: We conclude that there is a markedly increased prevalence of atrial
      fibrillation among patients with idiopathic central sleep apnea in the absence of
      congestive heart failure. Moreover, the high prevalence of atrial fibrillation
      among patients with idiopathic central sleep apnea is not explainable by the
      presence of hypertension or nocturnal oxygen desaturation, since both of these
      were more strongly associated with obstructive sleep apnea.

PMID- 16408412
TI  - Sleep stage 2: an electroencephalographic, autonomic, and hormonal duality.
AB  - STUDY OBJECTIVES: It is generally thought that the electroencephalogram of sleep
      stage 2 is not uniform, depending on whether sleep stage 2 evolves toward slow
      wave sleep (SWS) or toward rapid eye movement (REM) sleep. We provide here
      further evidence of the duality of sleep stage 2 on the basis of its autonomic
      and hormonal background. PARTICIPANTS: Fourteen healthy men (aged 21-29 years)
      underwent 1 experimental night. INTERVENTIONS: Sleep and cardiac recordings were
      taken from 11:00 PM to 7:00 AM. Blood was sampled continuously over 10-minute
      periods. MEASUREMENTS AND RESULTS: Autonomic activity, as inferred from heart
      rate variability analysis and hormone profiles, were examined with regard to the
      normalized hypnograms. We found a dual activity of the autonomic nervous system
      during sleep stage 2, with a progressive decrease in heart rate variability
      sympathetic indexes during the transition toward SWS contrasting with high and
      rather stable levels during sleep stage 2 that evolve toward REM sleep. Also,
      different profiles were observed in 2 major hormone systems, the activating
      adrenocorticotropic system and the renin-angiotensin system. Cortisol, in its
      active period of circadian secretion, was stable during sleep stage 2 preceding
      SWS and increased significantly when sleep stage 2 preceded REM sleep. For plasma
      renin activity, sleep stage 2 played a transitional role, initiating increasing
      levels that peaked during SWS and decreasing levels that reached a nadir during
      REM sleep. CONCLUSIONS: These results indicate an autonomic and hormonal duality
      of sleep stage 2 that is characterized by a "quiet" period preparing SWS and an
      "active" period preceding REM sleep. These differences may confer a fundamental
      role on this sleep stage in ultradian sleep regulation.

PMID- 16408414
TI  - Cortical excitability in obstructive sleep apnea syndrome: transcranial magnetic
      stimulation study.
AB  - STUDY OBJECTIVE: To investigate cortical motor area function in patients with
      obstructive sleep apnea syndrome (OSAS) during the daytime. DESIGN: The day after
      a nocturnal polysomnography, transcranial magnetic stimulation (TMS) of the motor
      cortex was performed recording Motor Evoked Potential from the first dorsal
      interosseous muscle of the dominant hand. We evaluated: 1) the relaxed motor
      threshold (RMT), 2) the threshold of the cortical silent period (CSP), 3) the
      duration of CSP elicited by five stimulus intensities (95%,100%,105%,130%, and
      150% of RMT). To estimate the influence of waking on TMS, recordings were
      performed five times in a day. The Epworth Sleepiness Scale (ESS), and Stanford
      Sleepiness Scale (SSS) were also measured. SETTING: The study was carried out in
      the Sleep and Evoked Potentials laboratories of the Don C. Gnocchi Foundation
      (ONLUS IRCCS) Pozzola tico, (Florence), Italy. PATIENTS: 10 patients with OSAS
      and 10 healthy volunteers. INTERVENTION: N/A Measurements and Results: In OSAS
      patients, ESS and SSS were significantly higher than in controls. Patients had a
      longer duration of CSP at 95%,100% and 105% RMT intensity at almost recording
      hours; with 130% of RMT stimuli intensity OSAS patients were significantly
      different at 10AM from controls and with 150% of RMT intensity the difference did
      not reach significativity. PaCO2 was significantly correlated with CSP duration
      elicited at 10AM with 95%, 100% and 105% of RMT stimulus intensities.
      CONCLUSIONS: We found alterations of motor cortical excitability in OSAS patients
      during the daytime. We believe that PaCO2 levels, acting probably on various ion
      channels or metabolic pathways, may change the excitability of motor cortex
      modifying excitatory and inhibitory cortical circuits.

PMID- 16408415
TI  - Acoustic reflection for nasal airway measurement in patients with obstructive
      sleep apnea-hypopnea syndrome.
AB  - STUDY OBJECTIVE: To measure nasal dimensions and explore relationships between
      these and patients' use of continuous positive airway pressure (CPAP) in patients
      with obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: Prospective
      single-blind study. SETTING: A tertiary-care, sleep disorders referral center.
      PATIENTS: Sixty OSAHS patients (52 men, mean age 51 years, body mass index (BMI)
      36.1 +/- 9.4 kg/m2). MEASUREMENTS: After in-vitro validation, acoustic reflection
      was used to measure the nasal minimal cross-sectional area (MCSA), mean area, and
      volume in OSAHS patients receiving CPAP treatment. Variables from sleep studies
      included the apnea-hypopnea index (AHI), titration pressure, and CPAP use (hours
      per night) after 3 months. Median MCSA was used to categorize subjects into small
      and large MCSA groups. Correlation and regression analyses were conducted to
      investigate the relationship between results of polysomnography and nasal
      acoustic reflection. RESULTS: At baseline the small and large MCSA groups were
      not different (P > .05) in BMI, age, mask type, or previous nasal stuffiness, but
      there were more women in the smaller MCSA group (P = .02). CPAP use was
      significantly lower in the small MCSA group (P = .007), but apnea-hypopnea index
      and titration pressure were indistinguishable between the 2 groups. Furthermore,
      CPAP use correlated significantly and positively with MCSA (r = 0.34, P = .008),
      mean area (r = 0.27, P = .04), and volume (r = 0.28, P = .03). Step-wise multiple
      regression models revealed that MCSA was a predictor of the CPAP compliance (R2 =
      0.16, P = .002), and MCSA (P = .001) and age (P = .04) were predictive factors of
      CPAP compliance (R2= 0.22). Nasal dimensions were not related to subjective nasal
      stuffiness. CONCLUSIONS: CPAP use in patients with smaller nasal passages was
      lower than in those with larger passages. Objective measurement of nasal
      dimension may be more reliable than subjective self-report of nasal symptoms in
      identifying patients with OSAHS who might struggle with CPAP therapy.

PMID- 16408416
TI  - Experimental restriction of sleep opportunity in children: effects on teacher
      ratings.
AB  - STUDY OBJECTIVE: To determine the effects of experimental restriction of sleep
      opportunity on teacher ratings of academic performance and behavior in healthy
      normal children. DESIGN: Home-based, within-subjects design in which participants
      followed 3 week-long sleep schedules-Baseline (self-selected), Optimized, and
      Restricted-while attending school, with order of conditions counter-balanced
      (Optimized and Restricted). PARTICIPANTS: Seventy-four children (39 boys; aged 6
      to 12 years, mean = 10) screened for medical and psychological health.
      MEASUREMENTS AND RESULTS: Teachers masked to assigned hours of sleep completed
      paper-and-pencil questionnaires at the end of each study condition. Questionnaire
      items were selected from several published measures. Summary scores included
      Academic Problems, Hyperactive-Impulsive Behaviors, Internalizing, Oppositional
      Aggressive, Sleepiness, Total Attention Problems, and Mean Severity of Attention
      Problems. Main effects of sleep condition were found forAcademic Problems,
      Sleepiness, Total Attention Problems, and Mean Severity of Attention Problems.
      Restricting sleep increased ratings of Academic Problems (medium effect) relative
      to both Baseline (P < .01, eta(p)2 = .11) and Optimized (P < .05, eta(p)2 = .10)
      conditions and increased the Mean Severity of Attention Problems (medium effect)
      relative to Baseline (P < .01, eta(p)2 = .12). CONCLUSIONS: These findings
      provide experimental support for widely held beliefs about the importance of
      sufficient time-in-bed for academic functioning in children. Reducing sleep
      opportunity had a direct effect on academic performance, as rated by teachers,
      even among healthy students with no history of behavioral problems or academic
      difficulty. Findings also support insufficient sleep as a direct source of
      variability in the manifestation of attention problems but not hyperactivity.

PMID- 16408417
TI  - Sleep/wake patterns derived from activity monitoring and maternal report for
      healthy 1- to 5-year-old children.
AB  - STUDY OBJECTIVES: To describe behavioral sleep/wake patterns of young children
      from actigraphy and mothers' reports, assess age-group and sex differences,
      describe daytime napping, and investigate the impact of family demographic
      variables on sleep-wake measures. DESIGN: Cross-sectional sample of children wore
      actigraphs for 1 week; mothers kept concurrent diaries. SETTING: Children studied
      in their homes. PARTICIPANTS: 169 normal healthy children in 7 age groups (12,
      18, 24, 30, 36, 48, and 60 months old); 84 boys and 85 girls. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: Nocturnal sleep/wake measures estimated from activity
      recordings using a validated algorithm; mothers' reports of nocturnal sleep/wake
      patterns and daytime naps obtained from concurrent diaries. Bedtimes and sleep
      start times were earliest and time in bed and sleep period times were longest for
      12-month-old children. Rise time, sleep end time, and nocturnal sleep minutes did
      not differ across age groups. Actigraphic estimates indicated that children aged
      1 to 5 years slept an average of 8.7 hours at night. Actigraph-based nocturnal
      wake minutes and wake bouts were higher than maternal diary reports for all age
      groups. Daytime naps decreased monotonically across age groups and accounted for
      most of the difference in 24-hour total sleep over age groups. Children in
      families with lower socioeconomic status had later rise times, longer time in
      bed, more nocturnal wake minutes and bouts, and more night-to-night variability
      in bedtime and sleep period time. Children with longer naps slept less at night.
      CONCLUSIONS: Individual differences in sleep/wake measures reflect
      characteristics of children, parents, or parent-child interactions.

PMID- 16408418
TI  - Sleep habits and insomnia in a sample of elderly persons in China.
AB  - STUDY OBJECTIVES: To examine sleep habits, insomnia, and hypnotic use in the
      elderly in China. DESIGN AND SETTING: A cross-sectional survey in 5 cities of
      Shandong, mainland China in 1997. PARTICIPANTS: Among 1,820 individuals aged 65
      and older who were sampled, 1,679 (92.2%) were interviewed at home, including 770
      men and 909 women. MEASUREMENTS: Asleep and demographic questionnaire that
      included the Pittsburgh Sleep Quality Index was used for interviews. RESULTS:
      Average bedtime of participants was 9:18 PM (SD = 2.2 hours), and morning rise
      time was 5:42 AM (SD = 1.0 hour). Reported night sleep duration was 7.1 hours (SD
      = 1.6) without age and sex differences. Regular napping was more common in men
      than in women (44.2% vs 28.0%). Of the sample, 32.9% reported frequent insomnia
      symptoms, and 8.9% had insomnia symptoms with daytime consequences. Multivariate
      analysis indicated that age 75 years and older (odds ratio = 2.0), female sex
      (odds ratio = 1.4), unmarried status (odds ratio = 1.7), frequent napping (odds
      ratio = 1.5), and poor perceived health (odds ratio, = 2.1) were associated with
      elevated risks for insomnia. Hypnotic use during the past month was reported by
      6.5% of the sample; women were 2 times as likely as men to use hypnotics.
      CONCLUSION: Sleep patterns in Chinese elderly may be characterized by going to
      bed early and waking up early. Insomnia symptoms are as common among Chinese as
      among Western elderly. Further study is warranted to examine the association
      between insomnia and aging per se in Chinese elderly.

PMID- 16408419
TI  - Physiologic indexes in chronic insomnia during a constant routine: evidence for
      general hyperarousal?
AB  - STUDY OBJECTIVES: It has been hypothesized that general hyperarousal, present
      during both sleep and wakefulness, may underlie chronic insomnia. The present
      study explored, under strictly controlled conditions, whether chronic insomnia is
      associated with altered physiologic markers of arousal, both in absolute levels
      and in terms of circadian rhythmicity, relative to controls. DESIGN: A 24-hour
      constant-routine protocol was implemented to assess physiologic measures.
      SETTING: The study was conducted in an isolated, temperature- and light
      controlled, sound-attenuated sleep laboratory. PARTICIPANTS: Eleven subjects with
      clinically diagnosed chronic insomnia were compared with 13 healthy matched
      controls. INTERVENTIONS: The subjects underwent physiologic parameter recordings
      and cognitive performance testing during 24 hours of total sleep deprivation
      under strictly controlled circumstances. MEASUREMENTS AND RESULTS: Cardiovascular
      parameters, free cortisol, and body temperature were subjected to mixed-model
      analysis of variance and mixed-model harmonic regression. Overall, no differences
      were found in either the absolute level or the circadian parameters (amplitude,
      phase) of these variables between the insomniacs and the control subjects.
      CONCLUSIONS: Although physiologic indexes of arousal were slightly elevated in
      the insomnia group relative to the controls, the differences between the groups
      were not statistically significant. This could have been due to a lack of
      statistical power or could reflect the actual absence of arousal in our sample of
      chronic insomniacs. Systematic interindividual level differences overwhelmed any
      differences between the 2 groups, making it unlikely that general hyperarousal
      was a critical underlying factor in our sample. Earlier findings of hyperarousal
      in insomnia during studies that allowed sleep may have been specifically related
      to the sleep state.

PMID- 16408420
TI  - Actigraphy scoring reliability in the study of osteoporotic fractures.
AB  - STUDY OBJECTIVES: The editing and scoring of actigraphy data are important for
      calculating variables that describe sleep. Scoring is dependent on marking time
      points for when a participant got in and out of bed, plus time when the actigraph
      was removed. This placement of time points is subject to error. We examined
      interscorer reliability to determine if files scored by 2 different people were
      comparable. DESIGN: Observational study. SETTING: Community-based. PARTICIPANTS:
      A subset of 36 women taken from the latest biannual visit of the Study of
      Osteoporotic Fractures. All women had actigraphy data scored by 1 scorer for the
      Study of Osteoporotic Fractures staff, plus a blinded rescoring by an expert
      scorer at a different site. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The
      outcomes of interest from actigraphy are duration of in-bed interval, total sleep
      time, sleep latency, sleep efficiency, wake after sleep onset, total nap time,
      and total daytime minutes of watch removal. Clearly documented actigraphy scoring
      procedures were used. There were no significant differences between the expert
      scorer and the study scorer in sleep outcomes (all P values >.16 from a paired t
      test). There was a small but statistically significant difference between scorers
      for watch removal times (mean absolute difference 3.4 minutes +/- 5.4, P=.02).
      The intraclass correlation coefficients showed a high level of agreement (range,
      0.84-0.99). CONCLUSIONS: Even in a large study with 2 scorers, it is possible to
      use actigraphy as a measure of sleep without introducing interscorer measurement
      error. Using well-documented scoring and data-gathering procedures are essential
      for data quality control.

PMID- 16408421
TI  - CSF hypocretin levels are normal in Huntington's disease patients.

PMID- 16408422
TI  - Melatonin treatment in Smith Magenis syndrome.

PMID- 16408423
TI  - [Treatment of substance dependence by a bio-cognitive model based on behavioral
      pharmacology].
AB  - We have introduced cognitive behavior therapy (CBT) into the treatment of
      substance dependence patients, which involves disease education and focused group
      therapy to obtain insight into the taking behavior and to establish concrete
      countermeasures to prevent relapse. We have created a bio-cognitive model based
      on biological aspects to explain the pathology of substance dependence.
      'Dependence' is a term in behavioral pharmacology defined as reinforced drug
      seeking and taking behavior. Changes in taking behavior are thought to occur due
      to the repetition of the reinforcement action of psychoactive substances in the
      reward system of the brain. Therefore, when intake desire is strong, it is hard
      for patients to control themselves, and there is a feature of difficulties
      considering the process of thinking in CBT. In other words, when craving becomes
      strong, a chain of behavior happens spontaneously, without schema, involving
      automatic thoughts. We think that the improvement of protracted withdrawal
      syndrome (PWS) and entire frontal lobe function are important in learning to
      discern distortion of cognition. When PWS is improved, a conflict is easy to
      bring about in the process of drug seeking and taking behavior. And, it is easy
      to execute avoidance plans (coping skills) which are established to cope with
      craving in advance. We think that a goal for treatment is to discern drug seeking
      and taking behavior with natural emotion. The recovery of PWS and frontal lobe
      dysfunction takes a long time with a serious dependence, so we must perform
      repetition of CBT. As the treatment introduction of involuntary admission cases
      is adequate or cases of 1 to 3 months of admission treatment based on voluntary
      admission are hard to treat, treatment to obtain insights into patients while
      carrying out repeated CBT using a bio-cognitive model and to improve PWS could be
      a possibility as one treatment for the pathology of diversified substance
      dependence.

PMID- 16408424
TI  - [Consideration of the concepts of "remission" and "cured" in schizophrenia: a
      male case who experienced schizophrenia with psycho-motoric excitation 30 years
      ago].
AB  - Since the era of Kraepelin and Bleuler, schizophrenia has been considered to be
      very difficult to cure. Even if all symptoms of its acute phase have disappeared
      completely, it is customary to use the terms say "remission" instead of "cured".
      The chief reason why they have been unwilling to say "cured" is that, even if the
      present state seems to be "cured", there will be surely another attack in near
      future, so, the non-symptomatic state should not be understood as "cured".
      Whether schizophrenic patients can be cured or not is one of the great problems
      of modern psychiatry. Is there no probability for them to be cured? Recently,
      after a 30 years gap, I came to meet a man who had had a schizophrenic attack of
      the psychomotoric type when he was 25 years old and had been sent to the mental
      hospital where I had been at work and, by chance, had engaged in his treatment.
      After about 5 months' of acute state, he came at, so to speak, "Residualzustand"
      (Conrad) for about 1 year and then got insight into his psychosis. After the
      discharge, he had visited me as an outpatient once a month regularly. About one
      year thereafter, the change of my work place made us separate from each other.
      Since then, he stopped visiting the doctor and also stopped taking anti-psychotic
      drugs. He married at 29 years old and had 2 daughters and a son. In addition, he
      had started to work for his father's business. After his father's death, he
      became the owner of 5 shops and the supervisor of 50 workers. Is he not yet
      "cured"? Is he only in the state of "remission" even now? According to the
      principle of Kraepelin and Bleuler, he is not "cured" yet, because he will surely
      have a psychotic exacerbation in future. I wonder then, what is the difference of
      the two concepts of "remission" and "cured", and how is it possible to change
      "remission" to "cured"? Even Bleuler, E. has written in his world-famous textbook
      that the longer the duration of remission after the last attack, the smaller the
      probability of the next attack, and that after about 5 years free of attack,
      another exacerbation would be very improbable. Supported by the experiences of
      Utena, Miya and so forth, I proposed a thesis that if a person who had undergone
      schizophrenic attack has been in complete remission for more than 10 years, he
      can surely be counted as "cured". To verify this probability about the outcome of
      schizophrenia, it is very important for us to observe any patient who has
      attained the state of complete remission, and to describe and report his state
      thereafter as long enough as

PMID- 16408425
TI  - [Spiritual care for patients facing death].

PMID- 16408426
TI  - Mental health problems after tsunami disaster in Aceh and Nias; immediate
      responses and future programs.

PMID- 16408427
TI  - Tsunami and the mental health services.

PMID- 16408428
TI  - [Open renal biopsy].

PMID- 16408429
TI  - [Transplant kidney biopsy].

PMID- 16408430
TI  - [Beneficial effects of combination therapy with losartan and low-dose
      hydrochlorothiazide in the treatment of essential hypertension].
AB  - Although strict blood pressure control is essential for the prevention of
      cardiovascular disease, there are many hypertensive patients whose current
      hypertension treatments are inadequate. Therefore, we designed a clinical study
      to evaluate the efficacy achieving a blood pressure reduction by combination
      therapy with losartan and a low-dose diuretic. In the 10 hypertensive patients
      treated with candesartan at 8 mg/day for more than 2 months, combination therapy
      with losartan at 50 mg/day and hydrochlorothiazide (HCTZ) at 12.5 mg/day was
      conducted for 3 months after the cessation of treatment with candesartan. Either
      immediately before the onset of combination therapy or 3 months after the
      treatment, the 24 hour ambulatory blood pressure(ABP) and pulse rate were
      measured every 30 minutes. Pulse wave velocity(PWV) and homeostasis model
      assessment insulin resistance index(HOMA-R) with fasting blood were also measured
      after 3 months. In the treatment with candesartan, the ABP was 134.4 +/- 8.7/88.1
      +/- 6.1 mmHg at 24 hours, 139.7 +/- 8.4/91.3 +/- 7.1 mmHg in the daytime, 123.8
      +/- 11.6/81.6 +/- 5.9 mmHg in the nighttime, and 139.3 +/- 10.3/92.3 +/- 7.3 mmHg
      in the early morning(6 : 00-8 : 00). After the switch to the combination therapy
      with losartan and HCTZ, the blood pressure changed to 126.8 +/- 9.3/81.6 +/- 7.0
      mmHg (p < 0.05/p < 0.05) at 24 hours, 130.6 +/- 12.0/84.2 +/- 8.5 mmHg (p <
      0.05/p < 0.05) in the daytime, 119.3 +/- 8.7/76.6 +/- 6.5 mmHg (NS/NS) in the
      nighttime, and 129.7 +/- 11.7/84.0 +/- 9.2 mmHg(p < 0.05/p < 0.05) in the early
      morning. However, both the changes in heart rate and PWV, and the differences in
      blood glucose, lipid and HOMA-R were not significant. Nonetheless, the blood
      pressure control for 24 hours was better using the combination therapy with
      losartan at 50 mg/day and HCTZ of 12.5 mg/day than in the treatment with
      candesartan at 8 mg/day alone. Since losartan decreases uric acid unlike other
      angiotensin receptor blockers, the combination therapy of losartan and a diuretic
      can be expected to provide one of the best therapies for essential hypertensive
      patients.

PMID- 16408431
TI  - [Clinical outcome assessment of membranous nephropathy].
AB  - Appropriate treatment of idiopathic membranous nephropathy (IMN) remains a
      controversial issue. Whereas some authors recommend a conservative approach,
      based on the considerable rate of spontaneous remissions, others utilize early
      immunosuppressive treatment for most nephrotic patients with IMN. Our
      retrospective study consisted of 34 patients who presented with IMN between the
      period from 1987 to 2002. The patients were divided into two groups based on the
      type of treatment they received the immunosuppressive group comprised 18 patients
      who received corticosteroids with/without other immunosuppressive drugs and the
      supportive group comprised 16 patients who were treated with anti platelet drugs
      as supportive therapy. The amount of proteinuria at the base line was
      significantly higher in the immunosuppressive group than in the supportive
      group(4.7 +/- 2.9 vs. 2.7 +/- 2.7 g/24 h). At the end of the follow-up, complete
      remission was achieved more frequently in the immunosuppressive group than in the
      supportive group(9/18 vs. 3/16). This suggests that immunosuppressive treatment
      has the effect of decreasing proteinuria. At the end of the follow-up, 3 patients
      in the immunosuppressive group and 2 patients in the supportive group showed
      renal insufficiency (serum creatinine concentration > or = 1.5 mg/dl). Side
      effects besides diabetes were not seen as a result of immunosuppressive
      treatment. Our findings suggest that immunosuppressive treatment in IMN cases
      appears to be beneficial for decreasing proteinuria, but the effect on prevention
      of renal failure was not evident.

PMID- 16408432
TI  - [A case of microscopic polyangitis with sepsis due to pyelonephritis].
AB  - A 69-year-old woman, who had been diagnosed with interstitial pneumonia at 66
      years of age, was admitted to our hospital because of high fever, purpura
      occurring on her arms and legs, and renal dysfunction. At the time of admission,
      her renal function had severely deteriorated (sCr 8.2 mg/dl, 24 h Ccr 6 ml/min),
      she had a severe high fever (BT 39.5 degrees C), back pain, a white blood cell
      count of 19,540/,microl, and a CRP level of 26.7 mg/dl. Blood and urine cultures
      yielded identical strains of E. coli. We diagnosed sepsis caused by
      pyelonephritis, and started intravenous meropenem trihydrate(MEPM) at 0.5 g/day.
      Her renal dysfunction was severe, so we started hemodialysis therapy.
      Immunological examination revealed the presence of ANCA-associated
      glomerulonephritis. Renal biopsy before steroid therapy confirmed the diagnosis
      of pauci-immune-type crescentic glomerulonephritis. Based on purpura and
      interstitial pneumonia, along with rapidly MPO-ANCA-positive progressive
      glomerulonephritis (RPGN) with acute renal failure, we diagnosed microscopic
      polyangitis (MPA). To treat sepsis and severe pyelonephritis, we started
      intravenous immunoglobulin 5 g (100 mg/kg)/day for 5 days before starting
      immunosuppressive steroid therapy (m-PSL 1 g/day, PSL 20 mg/day) for 3 days.
      These treatments improved her general condition and immediately improved her
      renal function. It is important to prevent infection during treatment using
      conventional immunosuppressive therapy. These findings suggest immunoglobulin
      therapy to be a safe immuno-suppressive treatment that is efficacious against
      ANCA-associated glomerulonephritis.

PMID- 16408433
TI  - [Three patients with nephrotic syndrome due to membranous nephropathy complicated
      by Sjogren's syndrome].
AB  - We describe three females patients (age 40, 62 and 63 y) with nephrotic syndrome
      due to membranous nephropathy complicated by Sjogren's syndrome(SS). The patients
      satisfied the criteria for SS, but not those for systemic lupus
      erythematosus(SLE). All of them developed nephrotic syndrome, and light
      immunofluorescence as well as electron microscopy of renal biopsy specimens
      revealed membranous nephropathy. Two were positive for the SS-A antibody, and the
      other was positive for the SS-B antibody. Two were complicated with primary
      biliary cirrhosis (PBC) and autoimmune thyroiditis, whereas the other was
      complicated with interstitial pneumonia, but not with either PBC or autoimmune
      thyroiditis. Prednisolone (PSL) with or without cyclophosphamide improved the
      nephrotic syndrome in two of the patients. In conclusion, some patients with SS
      might become complicated with nephrotic syndrome due to membranous nephropathy if
      another systemic autoimmune disease exists.

PMID- 16408434
TI  - [A case of anti-GBM-antibody positive rapidly progressive glomerulonephritis who
      was weaned from hemodialysis after combination therapy with steroid and
      plasmapheresis].
AB  - We report an anti-GBM antibody-positive crescentic glomerulonephritis patient who
      benefitted from maintenance hemodialysis 4 months after the initial treatment,
      which included steroid pulse therapy and plasma exchange. A-29-year-old male was
      referred to our hospital because of high fever, abnormal urinary findings
      (leukocytes 3+, protein 2+, occult blood 3+) and a moderate degree of azotemia(S
      Cr 2.9 mg/dl). C-reactive protein (CRP) was 18.9 mg/dl and antibiotics were
      administered intravenously for 7 days under the diagnosis of pyelonephritis. High
      fever persisted, however, and S-Cr increased to 9.2 mg/dl even though a
      sufficient volume of urine was maintained. Blood and urine cultures were negative
      for bacteria. A kidney biopsy was performed and cellular crescents were observed
      around the glomeruli. No abnormal finding was observed in the lung and the
      nasopharyngeal region. To treat the crescentic glomerulonephritis, steroid and
      cyclophosphamide were administered while hemodialysis was carried out
      simultaneously. Although P-ANCA and C-ANCA were negative, anti-GBM antibody was
      proven to be positive thereafter (169 U) and six sessions of plasmapheresis were
      additionally performed to remove the antibody. Two months after the last
      plasmapheresis, the reduced urine volume (300 ml/day) gradually returned to
      normal. Hemodialysis was terminated because the S-Cr concentration reached a
      plateau at 4 mg/dl. Repeated biopsy revealed marked glomerulosclerosis, hence
      hypertension treatment and a low protein diet were ordered. In conclusion,
      residual renal function might improve even after 4 months of hemodialysis in
      cases of intensively treated anti-GBM-positive crescentic glomerulonephritis,
      though consecutive renoprotective therapy is required.

PMID- 16408435
TI  - [Assessment of measured respirable dust sampler penetration and the sampling
      convention for work environment measurement].
AB  - The relationship between dust size and penetration for a static horizontal
      elutriator (Sibata C-30) was measured in calm air. The elutriator as a low-volume
      air sampler is widely used as a dust size classifier in work environment
      measurements. The actual penetrations were compared with the theoretical models
      of the sampler and with sampling convention for respirable dust in work
      environment measurement. The sampling convention was recently introduced into the
      Japanese standard for work environment measurement and is based on the ISO 7708
      respirable dust convention. The bias of sampled masses from the respirable dust
      was calculated for two flow rates of the sampler, i.e., 50% cut sizes of 4 microm
      and 5 microm, from measured penetration curves. The bias of the sampler was
      overestimated in the 5 microm, 50% cut condition and underestimated in the 4
      microm, 50% cut condition for most workplace sampling situations.

PMID- 16408436
TI  - [Sleep survey of medical residents at a National University Hospital].
AB  - In order to ascertain the workload and lifestyle of medical residents prior to
      the introduction of a new medical resident training system, 102 residents at a
      national university hospital were monitored for four consecutive weeks to
      ascertain their life habits. Valid responses were obtained from 76% of the
      respondents for a total of 2,722 person days. It was found that the average
      length of sleep was 5.7 h on weekdays and 6.8 h on weekends. Of the 102
      residents, 40% slept less than six hours a night and 17% slept less than five
      hours a night. The time spent sleeping was particularly short among surgical
      residents. Given that lack of sleep not only affects the health of the residents
      negatively, but also compromises the safety of medical care that they provide,
      the new medical residency training system will need to monitor and analyze the
      wellbeing, including sleep patterns, of medical residents.

PMID- 16408437
TI  - [Use of complementary and alternative medicines among factory workers:
      investigation of workers in manufacturing].
AB  - To elucidate the situation of complementary and alternative medicines (CAM) in an
      occupational health setting, workers in a factory of a housing construction
      business were surveyed using self-administered questionnaires on their
      utilization of CAM in the past 12 months, out-of-pocket expenditures on CAM and
      ordinary western medicines (OWM), and reasons for the use of CAM. A total of 263
      workers (84.3%) completed the questionnaires. Among them, 134 (51%) had received
      CAM therapy in the last 12 months: i.e. nutritional and tonic drinks (35.4%),
      supplements (16.3%), massage (13.7%), chiropractic or osteopathy (8.7%), health
      related appliances (6.5%), herb or kampo (3.4%), aromatherapy (1.9%), acupuncture
      (1.9%), or other therapy (1.5%). Reasons for the use of CAM was "the condition
      was not serious enough to warrant OWM" and "expectation of health promotion or
      disease prevention" for 70 (51.9%) and 53 (39.3%) subjects, respectively. Average
      annual out-of-pocket expenditures for CAM and OWM were 17,500 and 21,300 yen,
      respectively. It seems important to further widen awareness and knowledge of CAM
      in occupational health.

PMID- 16408438
TI  - [Study on actual situation of community industrial physicians for small and
      medium-sized enterprises and their involvement in community occupational health
      services].
AB  - The subjects of this study were 405 Japan Medical Association authorized
      industrial physicians, Community Industrial Physicians (CIPs), who belonged to
      the Shinjuku, Nakano, and Suginami Words' regional medical associations in the
      jurisdiction of the Shinjuku Labor Standards Inspection Office. Between November
      and December, 2003, the CIPs were mailed a questionnaire requesting information
      about their affiliations and activities, and as indicators of their willingness
      to participate in Community Occupational Health Services, they were asked about
      the pros and cons of having their names published as Industrial Physicians,
      and/or practitioners for Regional Occupational Health Centers, or Regular Health
      Checks. 152 replies were received, effective response rate of 37.5%, and among
      these 94 replies were from CIPs who work as part-time industrial physician.
      Overall, CIPs attend Community Occupational Health Services (COHS) voluntarily,
      and wish to participate in them more in the future. CIPs who work as part-time
      industrial physician have knowledge of working safety and hygiene and are
      providing advice and guidance on working conditions and environments. Also, they
      are well informed about support services for small and medium-sized enterprises
      which is thought to be connected with their willingness to participate in COHS.
      Furthermore, it is important that part-time CIPs activities are appreciated by
      their respective place of work.

PMID- 16408439
TI  - [Adipocytokines and diabetes in the elderly].

PMID- 16408440
TI  - [Treatment policy for elderly diabetic patients in preparation for the super-aged
      society].
AB  - Recently in Japan, as the elderly population has increased remarkably, the number
      of elderly patients with diabetes is rapidly increasing. Among the elderly
      diabetic patients, there are much differences in the physical, mental, and
      society viewpoints. Therefore the restrictions they suffer in daily life are
      multifarious. In the treatment policy of elderly diabetic patients, it is
      important that we evaluate their various backgrounds and so on synthetically and
      then provide the treatment which is suitable and tailored for each of them. We
      have to cure with the aim of not only prevention of being taken and progress of
      complications but also support and improvement of elderly diabetic patient's
      quality of life.

PMID- 16408441
TI  - [Epidemiology of elderly diabetes mellitus in Japan].
AB  - Glucose tolerance progressively declines with age, and there is a high prevalence
      of type 2 diabetes and post challenge hyperglycemia in the older population.
      Diabetes in the elderly is not a single entity, but a heterogeneous group of
      conditions. A further 9% may have undetected/asymptomatic hyperglycemia. Several
      studies have also shown that fasting blood glucose rises with age (about 1-2
      mg/dl/decade) and postprandial glucose by about 15 mg/dl/decade, leading to a
      mild glucose intolerance. Age-related glucose intolerance in humans is often
      accompanied by insulin resistance. The relative contribution of decreased insulin
      secretion vs. increased insulin resistance to the pathogenesis of type 2 diabetes
      mellitus has been the subject of long-standing controversy.

PMID- 16408442
TI  - [Japanese Elderly Diabetes Intervention Trial (J-EDIT)].
AB  - Treatment goals of medical care for the elderly patients with diabetes mellitus
      are maintaining high quality of life and elongating healthy longevity. In order
      to clarify how the elderly patients with diabetes mellitus should be treated for
      those purposes, a randomized controlled intervention study using 1,173 Japanese
      elderly patients with diabetes mellitus is now performing. All subjects have
      moderate or severe glucose intolerance. Subjects have been divided into two
      groups, ordinary treatment group and treatment group treated as same as adult
      patients with diabetes mellitus. The study has not been finished. Therefore,
      intermediate results were demonstrated and expectation for the study were
      discussed.

PMID- 16408443
TI  - [Tailored medicine for diabetes in the elderly].
AB  - To establish tailored medicine in the elderly, detailed information on clinical
      as well as genetic characteristics of each patient is essential. Although current
      age is all in the elderly, clinical characteristics of elderly patients with
      diabetes are very heterogeneous, making this category of patients good target for
      tailored medicine. Several genes conferring susceptibility to diabetic
      complications, such as insertion/deletion polymorphism of angiotensin--converting
      enzyme(ACE) gene for diabetic nephropathy, have been identified. Detailed
      information on genetic factor as well as current status of diabetes-related as
      well as unrelated complications will contribute a lot in establishing tailored
      medicine in elderly patients with diabetes.

PMID- 16408444
TI  - [Alteration of insulin secretion in the elderly].
AB  - Aging per se is associated with reduced insulin secretion, which is an important
      contributing factor for pandemic of diabetes worldwide. Although underlying
      mechanism for it is not fully elucidated, a combination of reduced beta cell mass
      and impairment of insulin granule handing in the cell is most likely which may be
      due to age-related mitochondrial dysfunction and/or dysregulation of
      transcriptional factors. For effective prevention of diabetes in the elderly
      population, restoration of beta cell function is desired. Meanwhile,
      identification of insulin-deficient elderly patients with diabetes and an earlier
      institution of insulin therapy for them are recommended for improvement of
      treatment outcome.

PMID- 16408445
TI  - [Possible role of mitochondrial dysfunction in insulin resistance in the
      elderly].
AB  - Both decreased insulin secretion and insulin resistance are two major factors of
      impaired glucose tolerance (IGT) in the elderly. Up to now, decreased lean body
      mass and relatively increased fat mass contribute to insulin resistance in the
      elderly. However, recent reports indicate that muscle mitochondrial function is
      reduced in aging, and this age-associated decline in mitochondrial function
      contributes to insulin resistance in the elderly. In addition, exercise
      intervention to IGT in the elderly is more effective to reduce in the incidence
      of type 2 diabetes than in younger people. Exercise seems to improve insulin
      resistance through mitochondrial function by activating AMP-activated protein
      kinase(AMPK) and PPARgamma coactivator-1alpha (PGC-1alpha).

PMID- 16408446
TI  - [Effects of aging on insulin resistance and fat accumulation].
AB  - Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and a
      risk factor for cardiovascular disease. Although the relationship between aging
      and insulin resistance has been well shown, precise mechanism of age-related
      insulin resistance still remain unknown. Insulin action may deteriorate with age
      mediated through accumulation of abdominal fat rather than aging per se. Recently
      it has been reported that intramyocellular lipid content and hepatic lipid
      content which are related to insulin resistance are increased in elderly.
      Alternation of fat distribution by aging may be related to age-related insulin
      resistance.

PMID- 16408447
TI  - [Clinical pathophysiology of the elderly onset diabetes mellitus].
AB  - Several studies have shown that fasting blood glucose rises about 1-2
      mg/dl/decade and post-prandial glucose by about 15 mg/dl/decade, leading to mild
      glucose intolerance with insulin resistance associated with aging. There appears
      to be a distinct group of individuals on an accelerated trajectory to clinically
      impaired glucose intolerance or frank type 2 diabetes mellitus. There are several
      characteristics of elderly onset type 2 diabetes as describe below. The incidence
      and progression of retinopathy were suggested to be rare. Several studies of the
      association between body mass index and cardiovascular mortality suggested the
      increased mortality associated with weight loss and underweight. Hypoglycemia is
      an underappreciated and potentially fatal complication of insulin and
      sulfonylurea treatment.

PMID- 16408448
TI  - [Diagnostic criteria for diabetes in older subjects].
AB  - The remarkable feature of glucose metabolisms in older subjects is that 2h plasma
      glucose concentration (2h-PG) increases linearly with age, but fasting plasma
      glucose concentration (FPG) does not. 2h-PG is a better predictor of the risk of
      mortality from cardiovascular disease (CVD) than FPG in older age as well as in
      young and middle age. Even subjects with isolated impaired glucose tolerance have
      a two times higher risk of CVD than those with normal glucose tolerance. Thus,
      the use of fasting glucose alone for diabetes diagnosis may fail to identify
      older adults at high risk for CVD and they should be evaluated by oral glucose
      tolerance test.

PMID- 16408449
TI  - [Guideline for the treatment of the elderly with diabetes mellitus].
AB  - The evidenced based guideline for the treatment of the elderly with diabetes
      mellitus was recently announced by the Japan Diabetes Society (JDS). The
      guideline states that the diagnosis of diabetes should be made in principle using
      the criteria established by the JDS. In the treatment of diabetes and associated
      complications, it is essential that appropriate treatment of diet therapy,
      physical exercise, oral hypoglycemic agent and/or insulin therapy be used, even
      in the elderly diabetic. This approach serves to improve glycemic control as well
      as to prevent the development and/or progression of diabetic microangiopathic and
      atherosclerotic diseases. Taking into account quality of life, safe and
      acceptable treatments should be considered in the elderly whose physiological,
      functional and socio-psychological abilities are known to decrease with advancing
      age.

PMID- 16408450
TI  - [Target of glycemic control of elderly diabetes mellitus patients].
AB  - Although the number of older diabetes mellitus patients is growing rapidly all
      over the world including Japan, there has been little evidence regarding the
      target of plasma glucose levels in elderly diabetes mellitus patients. Older
      persons with diabetes mellitus have higher rates of functional disability and
      coexisting illness. Plasma glucose levels should be controlled properly in
      elderly, however, the levels must be determined individually considering their
      complications. Because the risks of hypoglycemia, and/or drug-drug interactions
      are higher in the older patients, the medical providers must balance benefits and
      risks for every patient. RCT in older diabetes mellitus patients would be
      required.

PMID- 16408451
TI  - [Blood pressure control in eldery hypertension].
AB  - Case of diabetes mellitus associated with essential hypertension are mostly type
      2 diabetes mellitus(NIDDM) in elderly patients. In the JNC VI and JSH 2004, it is
      recommended that the therapeutic target blood pressure level should be lower then
      130/80 mmHg in hypertension complicated with diabetes mellitus, and this target
      has recently obtained wide acceptance. On the other hand, the target blood
      pressure in elderly is recommended below 140/90 mmHg. Accordingly, diabetes
      mellitus in elderly hypertensives should be treated similarly as in the young and
      middle-aged. Because ACE inhibitors/ARBs or Ca blockers increase insulin
      sensitivity, these drugs should be used as the first choice in cases of elderly
      hypertensive patients complicated with diabetes mellitus.

PMID- 16408452
TI  - [Exercise therapy for the aged diabetics].
AB  - The purposes of exercise therapy for diabetes are to improve insulin resistance
      and to prevent diabetic complications. At first, mild aerobic exercise (walking,
      cycling and swimming), which enhances insulin-signaling pathway, is recommended
      after medical check-ups. If aerobic exercise alone is not effective, the
      combination of aerobic and resistance training could be considered. The
      resistance training consists of rowing, lifting and dumbbells, and increases
      skeletal muscle volume and strength. This combination therapy would bring about
      not only improvement of insulin resistance but also restoration of quality of
      life for aged diabetic subjects.

PMID- 16408453
TI  - [Nutrition therapy for the elderly with diabetes mellitus].
AB  - The principles of nutrition therapy of diabetes mellitus are common for all
      generations. So the statements described in 'The clinical guideline of diabetes
      mellitus based on scientific evidence' (Japan Diabetes Association) are
      applicable for the elderly. However, the elderly diabetic patients have many
      problems peculiar to aging. The problems include physical, mental and emotional
      factors, which affect the eating patterns and the results of diabetic nutritional
      therapy. The elderly patient has his own diabetic history, diabetic complications
      and also has different environments including family, financial, social. So the
      healthcare provider has to lead the patient individually. Finally the diet is
      expected to be as diabetic diet but also to be as pleasure.

PMID- 16408454
TI  - [Knack of treatment with oral hypoglycemic drugs in the elderly].
AB  - In the treatment of elderly type 2 diabetes, it is important to detect
      hypoglycemia correctly, because the elderly patients often exhibit atypical
      symptoms from hypoglycemia. Oral hypoglycemic agents (OHA), which do not
      stimulate insulin release from pancreas, is rather safe and may be the first
      choice for the elderly patients. OHAs that stimulate insulin secretion weakly or
      temporally might be useful drug for controlling elderly diabetic patients
      characterized by post-prandial hyperglycemia. Strong-acting sulfonylurea must be
      use with a great caution. Importantly, once glycemic control comes to a fail even
      after an appropriate combination of OHAs, initiation of insulin injection therapy
      must be considered.

PMID- 16408455
TI  - [Insulin treatment in elder patients with diabetes].
AB  - Diabetes is a highly expanding health problem in Japan, especially for older
      people. The prevalence of glucose intolerance and diabetes increases with age. A
      postprandial hyperglycemia is the primary clinical manifestation. In older
      diabetic patients, atherosclerotic complications (macroangiopathies), as well as
      microangiopathies, are significant problems, threatening their quality of life.
      Though insulin therapy requires some special considerations, insulin is indicated
      for any patients with a poor glycemic control with oral agents. Single or
      multiple dose (s) of insulin injection therapy is selected for each patient to
      prevent symptomatic hyperglycemia, or to achieve near-normal glycemic control.
      Also, to maintain the quality of life for these older patients, hypoglycemia, as
      well as hyperglycemia, should be avoided. Newly developed insulin analogue (s)
      may be more appropriate for preventing hypoglycemia. Another method of prevention
      and treatment of hypoglycemia are discussed in this article.

PMID- 16408456
TI  - [Comprehensive geriatric assessment for management of the elderly with diabetes
      mellitus].
AB  - In medical care for the elderly patients with diabetes mellitus, there are many
      cases that are not indicated for active treatment, because of their impairment of
      activity of daily living (ADL), instrumental ADL and cognitive function, and also
      the presence of some complications, such as cerebrovascular disorder. On the
      other hand, poor glycemic control is easy to induce dehydration, bacterial
      infection, and cognitive disorders in the elderly. Thus, it is necessary to
      maintain good glycemic control to preserve better ADL. However, compulsion of
      strict glycemic control might rather decrease QOL of the patient. To solve such a
      medical dilemma, the comprehensive geriatric assessment (CGA) is useful for the
      individual diabetic patient.

PMID- 16408457
TI  - [Diabetic complications and their features in the elderly].
AB  - According to great increase in the number of patients with diabetes mellitus,
      especially in the elderly, it is important to know clinical features of diabetic
      complications in the elderly. In this review, we described elderly-specific
      clinical characteristics of diabetic complications. First, duration of diabetes
      in the elderly has a broad range, and as a consequence, elderly patients exhibit
      a remarkable heterogeneity in their complication status. Second, as acute
      complications, hyperglycemic coma and hypoglycemia are especially at high risk in
      the elderly. Third, as for chronic complications, such as retinopathy,
      nephropathy, neuropathy, diabetic foot, stroke as well as ischemic heart disease,
      several features in the elderly patients are different from those in the non
      elderly. Since these complications affect both quality of life and prognosis of
      the elderly, understanding these elderly-specific characteristics of diabetic
      complications would be necessary in the management of diabetes in the elderly.

PMID- 16408458
TI  - [Cognitive dysfunction and dementia associated with elderly diabetes].
AB  - Diabetes mellitus and cognitive decline are major public health concerns among
      the elderly. In diabetic subjects without dementia, certain cognitive domains are
      impaired, such as memory, attention, and executive/frontal lobe function
      (diabetic cognitive dysfunction). Recent epidemiological studies have suggested
      that diabetes increases the risks for vascular dementia as well as Alzheimer's
      disease. There are accumulating evidences that indicate biological linkage
      between impaired brain glucose metabolism homeostasis and cognitive decline.
      Diabetes may cause serious brain damages through several mechanisms and induce a
      variety of cognitive decline. Most critical issue to be resolved is to identify
      the mechanism of dementia leading from diabetic cognitive dysfunction. Once
      elderly diabetics had severe cognitive decline, effective treatment of diabetes
      were hardly obtained. Thus, diabetic cognitive decline should be considered as an
      important comorbidity of the elderly diabetes and long-term management of
      hyperglycemia is required from a view point to sustain healthy brain function. In
      this short review, we are summarizing the clinical features and current
      biological findings of diabetic cognitive decline. Also, we introduce the
      comprehensive treatment of demented diabetic elderly, including therapeutic
      strategy, nursing and care.

PMID- 16408459
TI  - [Sick-day management in elderly patients with diabetes mellitus].
AB  - Sick-day is defined as a state of common illness like cold or flu, which can
      reduce oral intake and make blood sugars hard to control in diabetic patients.
      The symptoms associated with hyper- or hypoglycemia may be atypical in the
      geriatric population, therefore, elderly patients need to take extra precautions
      on sick days to avoid diabetic crises. The elderly are particularly vulnerable to
      hyperglycemia and dehydration, the key components of hyperosmolar hyperglycemic
      syndrome, because insulin sensitivity and thirst mechanisms decrease with
      increasing age. Frequent monitoring of blood glucose is recommended and an
      individualized sick-day plan in considering the heterogeneity of older patients
      is important.

PMID- 16408460
TI  - [Caring for elderly patients with diabetes by understanding psychological
      status].
AB  - Managing diabetes effectively, people with diabetes have to follow many kinds of
      regimens. However, conducting many self-care behaviors are not easy for many of
      them. In making treatment plans for the elderly people, doctors should
      incorporate patients' perspectives for diabetes and it's treatment.

PMID- 16408462
TI  - [Strategies for the prevention of elderly-onset type 2 diabetes mellitus].
AB  - The recent medical statistics have revealed that the incidence of type 2 diabetes
      increased more rapidly in elderly people than that of manhood. Several randomized
      clinical trials to evaluate the strategies for preventing type 2 diabetes such as
      Diabetes Prevention Program (DPP), The Finnish Diabetes Prevention Study, The
      STOP-NIDDM, have been conducted. These studies suggested that a lifestyle
      intervention and treatment with antihyperglycemic agent inhibit the onset of
      diabetes in elderly people as well as manhood. However, the evidence for elderly
      people is not sufficient. The social and physical features of elderly persons
      should also been taken into account for the strategies to prevent the elderly
      onset type 2 diabetes.

PMID- 16408461
TI  - [Diabetes education in elderly patients to maintain quality of life].
AB  - The purpose of diabetes education in the elderly is to improve metabolic control
      and to maintain the quality of life. Diet should be weighted on maintenance of
      nutritional balance rather than energy restrictions. Simple dietary education
      program including point-to-point advices may be effective in elderly individuals.
      Resistance exercise as well as aerobic exercise should be recommended for
      prevention of atherosclerotic disease, osteoporosis, sarcopenia, and depression
      and for glycemic control. Self-monitoring blood glucose is an important measure
      to cope with hypoglycemia or sick days. In case of unstable dietary intake,
      sliding rules of insulin dose should be instructed to patients and their
      families. Psychological support is essential to patients and their caregivers who
      support diabetic patients having dementia, depression, and disabilities.

PMID- 16408463
TI  - [Therapeutic strategy for old age-onset diabetes mellitus].
AB  - Old-onset diabetes mellitus is often relatively mild in severity. However, if
      these patients develop marked hyperglycemia, they should be screened for the
      presence of malignancies, myocardial infarction and cerebral infarction. In
      addition, we should pay attention to the possible changes in the physical
      activities, medications and environmental status of the patients. There is no
      clear evidence how far we should lower blood glucose to prevent complications in
      those patients. Tight blood glucose control will, however, result in better
      prognosis in those patients with malignancies, myocardial or cerebral infarction.
      According to JDS, these patients are recommended to have less than 140 mg/dl of
      fasting plasma glucose and less than 7% of HbA1c. It is, however, necessary to
      respect the patient's will, efforts, and pride and is also necessary to adopt a
      flexible therapeutic strategy tailored to each patient's physical, psychological,
      and social status.

PMID- 16408464
TI  - [Role of the diabetes educator for elderly patients].
AB  - Diabetes is a heterogeneous disorder characterized by a genetic predisposition
      and interaction between insulin resistance and decreased pancreatic beta cell
      function. Elderly patients are often accompanied by other chronic conditions as
      well as additional risk factors for atherosclerosis and cardiovascular disease.
      In recent years in Japan, with extension of life expectancy, preventive measure
      both primary and secondary for senior citizens is increasingly important.
      Diabetes education for elderly patients is fundamentally the same as for much
      young group. The social background of the elderly is tremendously diversified.
      Therefore, the clinical decision-making has to be started with educational model,
      and complete primary care setting is necessary with exclusively individualized
      program understanding the ability of a key person in a support group.

PMID- 16408465
TI  - [Na+/Ca2+ exchanger(NCX1) and salt-sensitive hypertension].
AB  - Hypertension is the most common chronic disease, and is the leading risk factor
      for death caused by stroke, myocardial infarction, and end-stage renal failure.
      The critical importance of excess salt intake in the pathogenesis of hypertension
      is widely recognized. However, the molecular mechanisms underlying salt-sensitive
      hypertension remain obscure. Recent studies using selective inhibitors and
      genetically engineered mice provide compelling evidence that salt-sensitive
      hypertension is triggered by Ca2+ entry through Na+/Ca2+ exchanger type-1 (NCX1)
      in vascular smooth muscle. Intriguingly, endogenous Na+ pump inhibitors seem to
      be necessary for NCX1-mediated hypertension. These findings have enabled us to
      explain how high salt intake leads to hypertension, and further to describe the
      potential of vascular NCX1 as a new therapeutic or diagnostic target for salt
      sensitive hypertension.

PMID- 16408466
TI  - Clinical features of third open-heart valve surgery at the same valve position.
AB  - OBJECTIVE: Recently, there has been an increase in case of repeated open-heart
      valve surgery and the clinical results of the second surgery are only slightly
      worse than those of the first surgery. However, clinical results of the third
      open-heart valve surgery at the same position are rarely reported. Clinical
      features of third open-heart valve surgery at the same position are discussed in
      this study. METHODS: Between 1995 and 2004, 16 patients underwent third open
      heart valve surgery at the same valve position under cardiopulmonary bypass. The
      average age of the 16 patients, 12 females and 4 males, was 56 +/- 15 years.
      Clinical features of the 16 cases were retrospectively analyzed. RESULTS:
      Mechanical valve nonstructural dysfunction was the most common valve malady,
      followed by bioprosthetic valve dysfunction. The duration of surgery from skin
      incision to establishment of the cardiopulmonary bypass was 94 +/- 42 minutes.
      Myocardial ischemia time was 137 +/- 38 minutes and extracorporeal circulation
      time was 212 +/- 82 minutes. Early mortality was seen in 1 patient (6.25%) and
      late mortality was seen in 1 patient. CONCLUSION: Mechanical valve nonstructural
      valve dysfunction leads to repeated valve surgery. The clinical results of the
      third open-heart valve surgery at the same valve position are acceptable, and the
      mid-term survival is excellent.

PMID- 16408467
TI  - Surgery for aortic dissection involving an aberrant right subclavian artery.
AB  - On diagnosis of Stanford type A acute aortic dissection with an aberrant right
      subclavian artery, emergency operation was performed. Aortic arch replacement was
      undertaken with additional 'elephant trunk' procedure to cover the entry site and
      decrease the blood flow through the false lumen. We consider this technique will
      become one of the effective procedures for acute aortic dissection involving an
      aberrant right subclavian artery.

PMID- 16408468
TI  - Ross procedure in an infant weighing 4.5 kg: eight years follow-up.
AB  - A 6 month-old male infant (weight: 4.5 kg) with congenital aortic stenosis
      underwent aortic valve replacement with a pulmonary autograft (Ross procedure).
      The right ventricular outflow tract (RVOT) was reconstructed with a
      polytetrafluoroethylene (PTFE) -valved equine pericardial conduit. At the age of
      5, re-RVOT reconstruction with an equine pericardial patch bearing a PTFE
      monocusp was required because of severe pulmonary stenosis resistant to 2
      attempts of percutaneous transluminal pulmonary valvotomy. Currently, at the age
      of 8, the degree of aortic regurgitation is trivial and the pulmonary autograft
      is free of functional deterioration despite somatic growth.

PMID- 16408469
TI  - Vacuum-assisted closure system for the treatment of mediastinitis after total
      aortic arch replacement.
AB  - A 77-year-old man developed deep sternal wound infection with Enterobacter
      cloacae 4 days after total aortic arch replacement for distal aortic arch
      aneurysm. Reexploration and open drainage of the mediastinum was carried out for
      4 days, and the vacuum-assisted closure system was applied and continued for 10
      days. During the treatment, granulation formation and neovascularization was
      apparently enhanced which lead us to perform omental transfer and chest closure
      on the 18th postoperative day. The patient has been free from recurrent sign of
      mediastinal infection or graft infection for the 19 months of the follow-up
      period.

PMID- 16408470
TI  - Adult case of accessory cardiac bronchus presenting with bloody sputum.
AB  - We report an adult case of accessory cardiac bronchus (ACB) which extended from
      the carina to the diaphragm. A 32-year-old woman, with a history of frequent
      respiratory infections since childhood, recently presented with bloody sputum,
      and was admitted to our hospital. The ACB was detected as a supernumerary
      bronchus diverging from tracheal bifurcation. Complete resection of the ACB was
      performed by video-assisted thoracic surgery via minithoracotomy, approaching
      from the 5th intercostal space. The bloody sputum was caused by chronic
      inflammation of the ACB. She has been asymptomatic since surgery.

PMID- 16408471
TI  - Isolated right ventricular metastasis of uterine cervical carcinoma.
AB  - Isolated direct metastasis of uterine cervical carcinoma to the right ventricular
      endocardium is very rare. A 68-year-old woman was initially diagnosed as having
      stage IIIb squamous cell carcinoma of the uterine cervix, and was treated with
      radiation therapy. After 2 years, she developed heart failure and presented with
      a mass in the right ventricle. The results of further examinations were
      consistent with a tumor or a thrombus in the right ventricle. She underwent
      excision of the mass under cardiopulmonary bypass, and histopathologic
      examination of the resected tissue revealed metastatic squamous cell carcinoma of
      the uterine cervix. She was discharged 3 weeks after the operation, and underwent
      chemotherapy. However, she was readmitted with drug-induced interstitial
      pneumonia and died 5 months after the surgery. Patients with an intracardiac mass
      and a history of uterine cervical cancer should be suspected of having a
      myocardial metastasis until it is proven otherwise.

PMID- 16408472
TI  - Spontaneous hemothorax in patients with von Recklinghausen's disease.
AB  - Spontaneous massive intrathoracic bleeding is rare except for the rupture of
      aortic aneurysm or pleural adhesions in association with pneumothorax. We
      encountered two cases of critical massive hemothorax in patients with von
      Recklinghausen's disease (type I neurofibromatosis). Case 1; a 59-year-old female
      suddenly experienced severe back pain followed by syncope and shock. The
      hemothorax was caused by a bleeding of diffuse type neurofibroma of the parietal
      pleura and she underwent thoracotomy and surgical ligation of the bleeding
      vessels. Case 2; a 46-year-old male suddenly suffered back pain and fainted while
      driving. An intercostal aneurysmal rupture caused a spontaneous hemothorax and he
      underwent chest tube drainage followed by endovascular coil embolization. We
      reviewed 23 cases reported in the literature, including our two cases.
      Spontaneous hemothorax in patients with von Recklinghausen's disease is a life
      threatening syndrome and may require emergency surgical or endovascular
      embolization.

PMID- 16408473
TI  - Lymphoepithelioma-like carcinoma of the lung: case in which the patient has been
      followed up for 7 years postoperatively.
AB  - Primary lymphoepithelioma-like carcinoma (LELC) of the lung is a very rare
      disease. There is very little long term follow-up data about this disease. A 60
      year-old woman was found to have abnormalities according to a routine chest X-ray
      examination. She was admitted to our hospital in March 1998. Since a malignant
      tumor of the right lung was suspected, surgical resection was performed in April
      of the same year. Pathological diagnosis was LELC of the lung. Its pathological
      stage was T1N0M0 stage IA. It has been reported that this carcinoma is associated
      with Epstein-Barr virus (EBV) infection. However, the patient's tumor cells were
      negative for EBV as examined with RNA in situ hybridization technique. She is
      alive and has been free from recurrence of the disease over 7 years
      postoperatively.

PMID- 16408474
TI  - Aortic valve-sparing operation and a total arch replacement by an elephant trunk
      method for Marfan's syndrome with aortic regurgitation and a DeBakey type IIIb
      dissection.
AB  - A 35 year-old male with Marfan's syndrome was referred with a fortuitous
      echographic finding of an abdominal aorta flap. Transthoracic echocardiography
      showed moderate aortic regurgitation and an aneurysm in the sinus of Valsalva.
      Computed tomography demonstrated an aneurysm in the sinus of Valsalva 60 mm in
      size and a DeBakey type IIIb dissection extending from the left subclavian artery
      to the right common iliac artery. An aortic valve-sparing operation
      (reimplantation), total aortic arch replacement and the elephant trunk method
      were used in this patient. An aortic valve-sparing operation is preferable
      because the patient is young, and has no need for anticoagulant therapy after
      surgery. The extent of the aortic reconstruction, including the intact aortic
      arch, was appropriate to prohibit future dilatation of the aortic arch and
      retrograde dissection from a DeBakey type IIIb dissection.

PMID- 16408476
TI  - Nanotechnology and public health.
AB  - Nanotechnology is developing very quickly, and Japan is in many respects leading
      the world in this convergence of nanoscale engineering techniques. The public
      health community in Japan must start to think about the public health impacts of
      nanotechnology over the next 20 years. The responsibility for the benefits and
      the harms of nanotechnology lies with government, with corporations and the
      business community, with scientists and specialists in all related fields, and
      with NPOs and the public. There are very many questions of public health which
      are not yet being asked about nanotechnology. If nanoparticles are to be used in
      cosmetics, food production and packaging, how will they react or interact with
      the human skin and organs? What chemical-toxic effects on life might there be
      from the nanoparticles in car tires and vehicle plastic mouldings when they are
      disposed of by incineration? Will they pass into the soil and groundwater and
      enter into the food-chain? It is now an urgent ethical demand, based on the
      precautionary principle, that Japan join the governments of the world to take an
      intergovernmental initiative to intervene in the further development, production
      and marketing of nanotechnological products with precautionary research and
      regulation.

PMID- 16408475
TI  - Successful surgical treatment of a mycotic right coronary artery aneurysm
      complicated by a fistula to the right atrium.
AB  - We reported successful surgical treatment of a mycotic right coronary artery
      aneurysm complicated by a fistula to the right atrium in a 60-year-old man
      admitted to hospital because of acute worsening of renal function and
      erythroderma. After admission, he suffered from methicillin-resistant
      Staphylococcus aureus septicemia. Despite administration of vancomycin
      hydrochloride, a low-grade fever persisted. Subacute cardiac tamponade occurred
      three months after admission, and acute inferior wall myocardial infarction
      occurred two weeks after pericardial drainage. An emergent coronary angiography
      demonstrated a large saccular aneurysm of the right coronary artery forming a
      fistula to the right atrium and obstruction of the distal right coronary artery.
      We emergently resected the aneurysm including the right atrial wall and repaired
      the defect in the right atrium. Pathological examination of the aneurysmal wall
      revealed its mycotic nature; the postoperative course was uneventful.

PMID- 16408477
TI  - Evaluation of universal newborn hearing screening in Japan: an analysis of the
      literature.
AB  - INTRODUCTION: To address delayed language development associated with severe-to
      profound congenital hearing loss (CHL), universal newborn hearing screening
      (UNHS) has been implemented in many countries. In Japan, approximately 27,000
      neonates (2.5% of newborn) are screened annually through public-funded programs.
      While foreign literature highlights the need for assessment, in Japan this has
      hitherto not been evaluated in detail. OBJECTIVE: To investigate the efficacy of
      UNHS in Japan. METHODS: We used two criteria to evaluate UNHS; accuracy of
      screening and the effectiveness of early detection, and searched the major
      medical and social research journal data bases for related research papers.
      Eleven articles were identified providing information on accuracy of screening
      tests and two on effectiveness of early detection. RESULTS: 1) In two prefecture
      based studies, 900 and 1,272 newborns were screened to find one case of bilateral
      CHL. In nine hospital-based programs, the number tested ranged from 313 to 1,910.
      None of the studies measured the sensitivity and specificity against a best
      practice standard. 2) The two studies suggested that early intervention might be
      beneficial, but neither provided conclusive evidence. CONCLUSION: The
      effectiveness of UNHS in Japan is still equivocal because of the difficulties
      associated with differential diagnosis of hearing loss and normal hearing at the
      early stage of life and the lack of evidence on effectiveness of early
      intervention. Before nationwide implementation of UNHS, these issues should be
      fully investigated and evaluated.

PMID- 16408479
TI  - Competence necessary for Japanese public health center directors in responding to
      public health emergencies.
AB  - OBJECTIVE: To clarify the "competencies" required of public health center
      directors in "public health emergency responses." METHODS: We selected as our
      subjects six major public health emergencies in Japan that accorded with a
      definition of a "health crisis." Their types were: (1) natural disaster; (2)
      exposure to toxic substances caused by individuals; (3) food poisoning; and (4)
      accidental hospital infection. Item analysis was conducted using the Incident
      Analysis Method, based on the "Medical SAFER Technique." RESULTS: The
      competencies of public health center directors required the following actions:
      (1) to estimate the impact on local health from the "first notification" of the
      occurrence and the "initial investigation"; (2) to manage a thorough
      investigation of causes; (3) to manage organizations undertaking countermeasures;
      (4) to promptly provide precise information on countermeasures, etc.; and (5) to
      create systems enabling effective application of countermeasures against
      recurrence of incidents, and to achieve social consensus. CONCLUSION: For public
      health preparedness, public health center directors should have the following
      competencies: (1) the ability to estimate the "impact" of public health
      emergencies that have occurred or may occur; (2) be able to establish and carry
      out proactive policies; (3) be persuasive; and (4) have organizational management
      skills.

PMID- 16408478
TI  - Metabolic syndrome from the view point of public health: with special reference
      to nonalcoholic fatty liver disease.
AB  - Changes in human behavior and lifestyle over the last century have resulted in a
      dramatic increase in the incidence of obesity, type 2 diabetes, and the metabolic
      syndrome. Differences in the reported overall prevalence of the metabolic
      syndrome, which is generally in the range of 10-30% depend on the diagnostic
      criteria and subjects of the study. Recently, Japanese criteria for diagnosis of
      the metabolic syndrome were defined. With these criteria, presence of visceral
      obesity is essential for the diagnosis and is simply determined by measurement of
      waist circumference. Reflecting a dramatic increase in the incidence of obesity
      and type 2 diabetes, the incidence of the metabolic syndrome is increasing in
      Japan as well as in Western countries, regardless of the criteria applied.
      Recently, the number of workers with elevated liver enzymes, in whom virus
      hepatitis, alcoholic liver disease, drug induced hepatitis, autoimmune hepatitis,
      and iron overload were ruled out as causal agents, has also be found to be
      increasing at workplace health checkups. Most of such workers have components of
      the metabolic syndrome and the presence of steatosis in the liver, this
      pathologic condition now being termed nonalcoholic fatty liver disease (NAFLD).
      In this review, we describe the relationship between NAFLD and the metabolic
      syndrome.

PMID- 16408480
TI  - Refined method for estimating medical expenditures for liver disease using the
      patient survey and claim data in Japan.
AB  - OBJECTIVE: This study was performed to develop a estimation method for medical
      expenditures based on detailed data for the various kinds of liver disease.
      METHODS: Using claim data from the Survey of National Medical Care Insurance
      Services and the Patient Survey in Japan, we estimated the medical expenditures
      for various liver diseases using a refined method, in which the amount of
      expenditure by age and sex was multiplied by the respective numbers of patients.
      RESULTS: According to our estimates, the total medical expenditures per year for
      all liver diseases in Japan was 680 billion yen. The breakdown included: viral
      hepatitis (256 billion yen); malignant neoplasms of the liver and intrahepatic
      bile ducts (170 billion yen); cirrhosis of the liver (97 billion yen); other
      liver diseases (63 billion yen); chronic hepatitis (61 billion yen); and
      alcoholic hepatitis (33 billion yen). CONCLUSION: These are the first published
      estimates, not only for the total medical expenditure for all liver diseases, but
      also for individual categories. The method we employed in this study can readily
      be applied to estimate medical costs for other diseases.

PMID- 16408482
TI  - Three-year follow-up on the effects of a smoking prevention program for
      elementary school children with a quasi-experimental design in Japan.
AB  - OBJECTIVE: We performed the follow-up tests for three years for junior high
      school students by the quasi-experimental design to investigate the medium-term
      effect of smoking prevention education in the elementary school. METHODS: The
      intervention group consisted of 106 school students of three elementary schools
      and received a smoking prevention program in the elementary school. Moreover, the
      follow-up tests were conducted at each grade of junior high school, and the
      booster program was mailed. The comparison group consisted of 193 school students
      of another three elementary schools without the program. RESULTS: The
      intervention effects were recognized on knowledge up to the second grade of
      junior high school for boys and up to the third grade for girls, on awareness of
      the importance of not smoking at the second grade, and on the intention of
      smoking at the age of 20 for girls up to the first grade. On the other hand, the
      intervention effects were not recognized on smoking experience for boys and
      girls. However, increase of the rate of smoking experience was not significant in
      the intervention group, while it was significant in the comparison group.
      CONCLUSION: The effect of the program for three years was judged to be moderate.

PMID- 16408481
TI  - Knowledge of smoking-related risks and opinions on tobacco control by smoking
      status and education level in Japan.
AB  - OBJECTIVE: We aimed to examine knowledge of smoking-related risks and opinions on
      tobacco control by smoking status and education level in Japan. METHODS: We
      conducted a questionnaire survey in 2002 on a random sample of residents aged 20
      to 79 years in two neighboring districts of northern Japan. In a total sample of
      7,136, we analyzed data from 5,638 (79.0%) subjects (2,659 men and 2,979 women).
      RESULTS: The length of education was positively associated with knowledge of
      smoking-related risks. Compared to current smokers, past male smokers and never
      female smokers were more likely to know about the harm of passive smoking. As for
      causal links between smoking and lung cancer, stroke, and low birth weight, those
      who had been educated longer tended to be more aware of the associations in both
      sexes. Compared to current smokers, past and never smokers of men and past
      smokers of women were more likely to know that smoking contributes to low birth
      weight, but no difference was observed between current and never female smokers
      in this regard. Opinions on tobacco control were associated with both smoking
      status and education level; past and never smokers compared to current smokers
      and those who were educated longer tended to be affirmative about tobacco
      control. CONCLUSION: Knowledge of smoking is largely associated with education,
      but opinions on tobacco control are dependent on both smoking status and
      education.

PMID- 16408483
TI  - Change of components of the metabolic syndrome in a workers' health checkup after
      five years--relation with elevated liver enzymes, gene polymorphisms for ALDH 2,
      beta3-AR and lifestyle.
AB  - We previously reported that the prevalence of elevated alanine aminotransferase
      (ALT) increases with accumulation of metabolic syndrome components, and a greater
      degree of involvement of aldehyde dehydrogenase 2 (ALDH2) than beta3-adrenergic
      receptor gene (beta3-AR) polymorphisms. The present study was designed to clarify
      the effect of aging, lifestyle and the two gene polymorphisms on the relationship
      between 4 components of the metabolic syndrome (obesity, hypertension,
      dyslipidemia and impaired glucose tolerance) and elevated ALT values in a subset
      of 73 out of 148 male workers who were 35 years of age in the baseline study and
      40 years old in the present study. Study subjects completed questionnaires about
      drinking and smoking habits, and underwent urinalysis, physical examination and
      peripheral blood tests, blood chemistry, electrocardiogram and chest X-rays each
      year as required by Japanese law. Information from the questionnaires and
      physical examinations, including liver function tests, were compared with
      previously reported ALDH2 and beta3-AR genotypes for the 73 workers. Of the 73
      workers studied, 14 (19%) demonstrated decrease in metabolic syndrome components,
      39 (53%) demonstrated no change, and 20 (27%) demonstrated an increase. Ten
      workers (14%) showed liver dysfunction at age 35 and 20 workers (27%) at age 40.
      Fourteen workers were newly diagnosed as having liver dysfunction at their 40
      year checkup, thus being associated with the BMI and an active ALDH2 genotype.
      Accumulation of components of the metabolic syndrome were associated with the
      presence of liver dysfunction at 35 years. In conclusion, these findings indicate
      that ALDH2 genotyping as well as lifestyle habits may be important factors in
      causing metabolic syndrome with liver dysfunction.

PMID- 16408484
TI  - Association of change in the type of job with prevalence of components of the
      metabolic syndrome-special reference to job stress.
AB  - OBJECTIVE: It is well established that job stress is a leading cause of
      cardiovascular disease. The relationship with the metabolic syndrome, however,
      has received only limited attention. The present study was designed to
      investigate associations between change of the type of job and the prevalence of
      metabolic syndrome components from the aspect of on-the-job stress and alteration
      in life style. METHODS: Thirty-six male workers of the manufacturing department
      were transferred to the carsales department at the same automobile company in
      1992 to 1993. These same workers were transferred back to the manufacturing
      department after two years. We compared the first health-check data before the
      transfer in 1992 (Term A), a second set of data two years after transfer in 1994
      95 (Term B) and a third set of data two years following transfer back to the
      manufacturing department in 1996-1998 (Term C). The workers were requested to
      provide information about drinking and smoking habits, and answer Karasek's
      questionnaire and a simple stress questionnaire in order to clarify the
      possibility of job stress in occurrence of the metabolic syndrome, defined in
      terms of obesity, hypertension, dyslipidemia, and impaired glucose tolerance as
      components. RESULTS: Five workers had two or more components of the metabolic
      syndrome before the transfer to the car-sales department (Group I). One
      demonstrated improvement, three no change, and one increase in symptoms from A to
      B. Seven workers had more than two components after the transfer to car-sales
      department (Group II), and six of them exhibited decrease two years following
      transfer back to the manufacturing department. Five of them also showed elevated
      liver enzymes in serum with the appearance of the components, and three of them
      demonstrated recover. Three workers had two components of the metabolic syndrome
      only at time point C (Group III), while the remaining 21 workers had 0 to one
      component throughout the observation period (Group IV). Amount of drinking and
      smoking increased significantly when working in the sales department but these
      items returned to the previous values after rejoining manufacturing, though
      differences were not observed between workers with (Group II) and without (Group
      IV) components of the metabolic syndrome. Body mass index (BMI) and alanine
      aminotransferase (ALT) increased significantly when workers moved to the sales
      department and that was significant in Group II as compared to Group IV. Three
      components of Karasek's JCQ changed significantly during job transfer, though
      differences were not observed between the workers with (Group II) and without
      (Group IV) components of the metabolic syndrome. Logistic regression analysis
      with age, lifestyle, Karasek's JCQ, and ALT revealed that elevation of ALT value
      was associated with having two or more components of metabolic syndrome, while
      hours of sleep demonstrated an inverse association. CONCLUSION: Elevated ALT and
      reduction of sleep hours may be associated with development of the metabolic
      syndrome in workers who change their type of job.

PMID- 16408485
TI  - Analysis of administrative sanctions and criminal prosecutions of doctors in
      Japan.
AB  - OBJECTIVES: To illustrate how administrative sanctions (AS) and criminal
      prosecution (CP) differ with regard to application with doctors' misconducts.
      METHODS: A total 465 doctors who were punished twice by AS and CP were analyzed
      using the proportional distribution method (PDM) to break down into the charge
      specific months of suspension or imprisonment. RESULTS: Overall, the Minister of
      Health, Labor & Welfare (MHLW) sanctioned doctors by suspending their licenses
      for twice the number of months that the court ordered for imprisonment. Charge
      specific analysis of months (suspension or prison terms) revealed a different
      pattern of judgment. The MHLW judged obscenity more unethical, allocating a
      larger share of the total months of suspension to punish this misconduct, but
      judged bribery less unethical allocating a smaller share of the total months of
      suspension to punish this than the court. For traditional crimes like swindling,
      murder and psychostimulant abuse, both judgments followed similar patterns
      allocating the same share of months for punishment of such acts. DISCUSSION: CP
      and AS were shown to have different patterns in their judgments of doctors'
      crimes or misconducts reflecting the different purposes they pursue: justice by
      CP and ethics by AS. (186 words).

PMID- 16408486
TI  - Factors associated with successful smoking cessation among participants in a
      smoking cessation program involving use of the internet, e-mails, and mailing
      list.
AB  - OBJECTIVE: The objective was to clarify factors, including Internet-accessed
      advice for smoking cessation, associated with smoking cessation among
      participants of the Quit Smoking Marathon (QSM), a one-month smoking cessation
      program involving use of e-mails and a mailinglist. METHODS: The subjects were 88
      volunteers who aimed to quit smoking and completed the QSM program. Those who
      remained abstinent from smoking at 1 year thereafter were defined as successful
      quitters. Factors associated with successful smoking cessation were examined by
      multiple logistic regression analysis adjusted for confounders and separately for
      use of nicotine replacement therapy (NRT). RESULTS: Successful smoking cessation
      was reported by 49 subjects (55.7%). For the NRT-free group, sending 10 or more e
      mails to the mailing-list was significantly associated with successful smoking
      cessation [odds ratio: 10.7, P=0.015]. CONCLUSION: Frequent e-mailing to the
      mailing-list followed by obtaining personal advice is an effective way to quit
      smoking among QSM participants not using NRT.

PMID- 16408487
TI  - [New pharmacological treatment for the ocular diseases].

PMID- 16408489
TI  - [Studies on exogenous and endogenous factors associated with various ocular
      diseases].
AB  - The exact cause and nature of various ocular diseases are still unknown. In
      accordance with the progress of modern medical science, technology for research
      investigations has greatly developed and a variety of new results have recently
      been produced. However, they were mostly about exogenous factors such as bacteria
      or parasites. On the other hand, molecular biology has markedly progressed in the
      second half of the 20th century and has been applied to medical science. As for
      the exogenous factors, molecular techniques have been introduced to the diagnosis
      of infectious diseases, and their diagnosis has become much easier and much more
      exact than before. Similarly, in the field of immunogenetics, molecular genetics
      has greatly developed, and disease susceptibility or disease resistance has been
      investigated at the DNA or molecular level. Regarding the exogenous disease
      mechanisms, most infectious diseases occur when the microorganisms are
      transmitted to some individuals. In this case, endogenous factors play almost no
      or very little role. Adenovirus keratoconjunctivitis is one example. Human
      adenovirus (HAdV) is a DNA virus. Although HAdVs are classified into 51 different
      serotypes, only 7 of them such as HAdV-3, -4, -7, -8, -11, -19, and -37 usually
      develop acute keratoconjunctivitis. The genome of HAdV develops constant
      mutation, and new genome types often cause epidemics of nosocomial infections.
      Recent studies showed that most of the keratoconjunctivitis cases are caused by
      HAdV-37 in Japan. With regard to the endogenous disease mechanisms, only 30 years
      have passed since the recent molecular genetic studies on disease susceptibility
      started. Before that, genetic disease mechanisms were studied only in hereditary
      diseases such as color vision defects, which follow the modes of Mendelian
      inheritance. Therefore, the presence of disease susceptibility was not clearly
      understood in the so-called nonhereditary diseases. However, after our initial
      findings of the close association between Behcet's disease and HL-A 5 (later HLA
      B 5 or HLA-B 51) in 1973, there were many reports on the presence of genetic
      predisposition to certain non-hereditary diseases. One example is Vogt-Koyanagi
      Harada's (VKH) disease which has a close association with HLA-DRB 1*0405 in
      Japanese patients, as also was the case with sympathetic ophthalmia. These
      studies indicate that Behcet's disease may be called "a disease of the Yayoi
      people" and Vogt-Koyanagi-Harada's disease as "a disease of the Jomon people"
      when analyze the associated genetic factors. On the other hand, the human genome
      project has been successfully completed and it is now possible for us to
      investigate any genetic factor associated with certain diseases either on 22
      pairs of autosomal chromosomes or on one pair of sex chromosomes. Our
      collaborative team has adopted the microsatellite methods utilizing the pooled
      DNA PCR method, and started investigation of any genetic association with ocular
      diseases, in addition to the HLA system on the short arm of autosomal chromosome
      6. In the first screening of 100 DNA samples of Behcet's disease patients, for
      example, 9 % of microsatellite markers on the autosomal chromosomes 1, 6, 17, and
      19 showed significant positive association. The same studies are now in progress
      by our collaborative team on inflammatory diseases such as sarcoidosis, and on
      noninflammatory conditions like hypertension or high myopia. These results
      suggest that exogenous environmental factors such as infections which may trigger
      the occurrence of the disease or conditions, and endogenous genetic factors which
      may predispose someone to contracting a disease, are both significantly
      associated with various ocular diseases, and construct intricate disease
      mechanisms. Therefore, in future studies of diagnosis, treatment, and prevention
      of various ocular diseases, both exogenous factors and endogenous factors have to
      be carefully analyzed and investigated.

PMID- 16408488
TI  - [Investigation of mechanism of cell proliferation regulation and its clinical
      application].
AB  - Cell proliferation and related cellular behavior in ocular neoplastic disease and
      in the healing process in ocular surgery or post-injury management, as well as
      new treatment strategy were investigated. The roles of growth factors and their
      signal transduction pathways were studied. Cell proliferation-related signals
      were found to be activated to a greater extent in malignant ocular tumors than in
      benign tumor cells regardless of the similarity of simple histological findings.
      Suppression of cell proliferation-related signals can be a new treatment for
      ocular neoplastic diseases. The causes of complications associated with tissue
      repair response include acceleration of cell proliferation and extracellular
      matrix expression and cellular phenotypic alteration, i. e., epithelial
      mesenchymal transition. These cellular activities can be controlled by modulation
      of growth factor signaling by employing such strategy including gene
      introduction.

PMID- 16408490
TI  - [New understanding and development of medical treatments for ocular diseases
      based upon molecular mechanisms].
AB  - A number of genes associated with life phenomena have been identified by the
      achievement of genome projects. As both comprehensive analysis and methods for
      investigation of specific genes have been developed, we can understand the
      pathogenesis of ocular diseases and develop novel medical treatments based upon
      detailed information on molecular mechanisms. In our review article, we focused
      on three vision-threatening ocular diseases; glaucoma, age-related macular
      degeneration (AMD) and proliferative vitreoretinopathy (PVR), and discussed the
      potential and problems related to retinal regenerative therapy. Regarding
      glaucoma, we investigated the relationships between aqueous humor and cell
      components in the aqueous outflow route. We have revealed that the Rho-Rho
      associated coiled-coil-forming protein kinase (ROCK) signal transduction pathway
      participates in regulation of the aqueous outflow route, and that ROCK inhibitors
      and several protein kinase inhibitors exert intraocular pressure-lowering
      effects. Also, we conducted a series of investigations on familial amyloidotic
      polyneuropathy (FAP), as a representative secondary glaucoma caused by genetic
      mutations in a single gene. We reviewed the clinical features of ocular
      complications derived from FAP, their molecular mechanisms and possibilities for
      the development of novel medical treatments. In addition, we discussed a novel
      therapeutic concept, "neuroprotection", and showed the potential of some drugs as
      candidates for the neuroprotective treatment of glaucoma. Against AMD, we have
      performed a series of experiments from the viewpoint of similarity with
      atherosclerotic lesions. We have shown the molecular mechanisms of AMD associated
      with up-regulated expression of scavenger receptors and the interaction between
      leukocytes and vascular endothelial cells. Furthermore, in the pathogenesis of
      PVR, we described the role of epithelial-mesenchymal transition in retinal
      pigment epithelial cells and demonstrated the usefulness of enzymatic vitrectomy.
      Although retinal regenerative therapy has attracted much attention from global
      investigators, we pointed out its limitation for clinical application, and
      developed researches on efficient culture method using physiologically active
      factors for proliferating retinal stem cells with multi-potentiality,
      differentiation of the transplanted progenitor cells, and axon guidance of
      neurons by extracellular matrices.

PMID- 16408491
TI  - [New medical treatment for viral conjunctivitis].
AB  - Around one million people in Japan are suffering from adenoviral conjunctivitis
      every year and it is recognized as one of the major pathogens of nosocomial
      infection. Several complications, such as corneal erosion and conjunctival
      pseudomembrane, are observed in some of the cases and corneal sube- pithelial
      opacity may bring visual impairment. Moreover, no specific anti-adenoviral agent
      has been discovered and an effective treatment has not been established for
      adenoviral infection. We have researched new medical treatment for viral
      conjunctivitis based on recent findings in adenoviral conjunctivitis. Firstly,
      anti-adenoviral activity was evaluated in vitro in agents which could possibly
      act as anti-adenoviral drugs. Twelve candidates, such as zalcitabin, interferon
      beta, etc., were selected among antiviral drugs, adenoviral receptor inhibitors,
      natural products and anti-inflammatory drugs. Remarkable anti-adenoviral effect
      was observed in zalcitabin, sanilbudine, interferon beta and anti-osteopontin
      peptide. Two anti-human immunodeficiency virus (HIV) drugs with anti-adenoviral
      activity, zalcitabin and sanilbudine, are nucleoside reverse transcriptase
      inhibitors, but, in contrast, non-nucleoside reverse transcriptase inhibitors and
      protease inhibitors were ineffective against adenovirus. Interferon beta and anti
      osteopontin peptide displayed anti-adenoviral effects by absorption inhibition.
      Secondly, side effects caused by possible anti-adenoviral eye drops, including
      cidofovir whose development as eye drops against eyeball and ocular adnexa had
      been suspended, were analyzed in a white rabbit model. In animals given cidofovir
      locally, significant narrowing of lacrimal canaliculus, redness of eyelid and
      conjunctival injection was observed, but obstruction of the lacrimal duct was not
      found. Although zalcitabin and sanilbudine eye drops induced eyelid redness, no
      change was observed in the lacrimal route and conjunctiva. In animals treated by
      cidofovir, inflammation histologically suggesting mainly allergic change was
      observed. These results indicate that these four drugs are possible candidate for
      safe eye drops against adenoviral conjunctivitis. These four agents are divided
      into two categories, inhibitors of adenoviral replication, zalcitabin and
      sanilbudine; and suppressors of adenoviral infection, interferon beta and anti
      osteopontin peptide. It is expected that eye drops for specific treatment of
      adenoviral conjunctivitis are going to be available in the near future following
      investigation of therapeutic effect in adenoviral infected animals and clinical
      trials in humans.

PMID- 16408492
TI  - [Cell-cell and cell-matrix interactions during cartilage formation].

PMID- 16408494
TI  - [Recent development and future direction of anti-aging therapy by supplements].

PMID- 16408493
TI  - Adult rhabdomyosarcoma in the nasal and paranasal sinuses showing complete local
      response to a combination of chemotherapy and radiotherapy using 3D-CRT and IMRT.
AB  - We report on a 69-year-old woman with rhabdomyosarcoma arising from the nasal and
      paranasal sinuses. She was referred to our hospital with a reduced ability to
      smell and impaired bilateral vision, narrowing of the visual field, and left
      facial pain. Computed tomography (CT) revealed a large tumor in the nasal and
      left paranasal sinuses invading the left orbital cavity and anterior skull base,
      and lymph node swellings in the submental and left accessory nerve areas. A
      biopsy specimen from the nasal tumor was diagnosed histologically as a
      rhabdomyosarcoma, alveolar type. Because the intracranial direct invasion and
      distant metastases to the thoracic spine were suspected by pretreatment
      examination, our case was determined to be inoperable by a head and neck surgeon.
      Radiotherapy with a total dose of 60 Gy was carried out to control the primary
      disease. The three-dimensional conformal radiotherapy (3D-CRT) and intensity
      modulated radiotherapy (IMRT) techniques were used in order to reduce the doses
      to risk organs. Combined with radiotherapy, chemotherapy was also performed for
      the treatment of lymph-node metastases and distant diseases. After the treatment
      was completed, the primary tumor and lymph-node metastases disappeared
      completely; there was no sign of re-growth during the follow-up period.
      Chemoradiotherapy may be an effective treatment also for inoperable adult
      rhabdomyosarcoma in the head and neck region. Furthermore, the 3D-CRT and IMRT
      techniques are both useful methods of radiotherapy for this disease.

PMID- 16408495
TI  - [Cost-utility analysis of osteoporosis].

PMID- 16408496
TI  - [Advances in regenerative medicine for skin].
AB  - A typical engineered product is autologous cultured epidermal substitute, which
      is composed of stratified keratinocytes (in USA). There are two types of
      allogeneic cultured dermal substitute (CDS) composed of fibroblasts combined with
      a synthetic scaffold (in USA). Another product is allogeneic cultured skin
      substitute, which is composed of keratinocytes and fibroblasts combined with a
      collagen gel (in USA). Recently, however, the commercialization of these
      allogeneic products has been discontinued. There seem to be some problems in the
      design of these products. Kuroyanagi et al. developed an allogeneic CDS composed
      of a fibroblast combined with a 2-layered spongy matrix of hyaluronic acid and
      collagen. A multicenter clinical study on the use of allogeneic CDS was performed
      in 30 hospitals across Japan as the Regenerating Medical Millennium Project of
      the Ministry of Health, Labor and Welfare. The results of clinical study suggest
      that this type of allogeneic CDS can effectively promote the healing of full
      thickness severe skin defects, such as chronic ulcers and burn injuries.

PMID- 16408497
TI  - [Sex difference of senescence and diseases in the elderly the growing importance
      of gender-specific geriatric medicine].

PMID- 16408498
TI  - [Gender difference of health expectancies].

PMID- 16408499
TI  - [Pathological aging and sex difference].

PMID- 16408500
TI  - [Cardioprotective effect of estrogen].

PMID- 16408502
TI  - [Prostatic diseases in aging men].

PMID- 16408501
TI  - [Sex steroids and metabolic syndrome].

PMID- 16408503
TI  - [Age and gender difference in rheumatology].
AB  - Most collagen diseases are more common in women except polyarteritis nodosa, but
      aging makes this gender difference smaller in some of the diseases. In systemic
      lupus erythematosus the incidence difference between men and women diminishes
      while Sjogren syndrome is more common in women at all ages. Diabetes mellitus and
      hyperlipidemia are also very common complications with steroid treatment. DM is
      more common in those aged over 45 years old. On the contrary, hyperlipidemia is
      common at all ages with the peak in those 45-54 years old and only 22% over 75
      years old have hyperlipidemia. According to the introduction of aggressive
      therapy for rheumatoid arthritis, complications in the elderly should be
      carefully managed.

PMID- 16408504
TI  - [Genetic aspects of osteoporosis; current status and future prospects].

PMID- 16408505
TI  - [The economic and social costs of geriatric diseases].

PMID- 16408506
TI  - [Acute myocardial infarction: characteristics and management in the elderly].

PMID- 16408508
TI  - [Surgical treatment of the lung cancer in elderly patients].

PMID- 16408507
TI  - [Molecular pathology and therapeutic perspectives of Alzheimer's disease].

PMID- 16408510
TI  - [Home medical care in the elderly].

PMID- 16408509
TI  - [Current concepts of vascular calcification].
AB  - Vascular calcification, such as coronary and aortic calcification, is a
      significant feature of vascular pathology. Two distinct forms of vascular
      calcification are well recognized. One is medial calcification, which occurs
      between the cell layers of smooth muscle cells, and is related to aging, diabetes
      and chronic renal failure. The other is atherosclerotic calcification, which
      occurs in the intima during the development of atheromatous disease. It has been
      shown that statins inhibit the progression of calcification in the aortic valve
      and the coronary artery. We have found that statins inhibit calcification of
      human aortic smooth muscle cells, which is induced by incubating the cells in
      high-phosphate medium. We also found that this is mediated by inhibiting cellular
      apoptosis, an essential mechanism for calcification, not by inhibiting inorganic
      phosphate (Pi) uptake by sodium-dependent phosphate cotransporter (NPC). Besides
      apoptosis and Pi uptake, such proteins as osteoprotegerin (OPG), matrix Gla
      protein (MGP), Klotho, fetuin-A, and apoE have been shown to negatively affect
      vascular calcification. Many previous reports suggest that vascular calcification
      appears to be regulated by promoting factors, such as Pi, apoptosis, modified
      LDL, advanced glycation end products, oxidative stress, vitaminD3,
      glucocorticoid, cbfa-1, osteopontin, and inhibitory factors, such as OPG, MGP,
      Klotho, fetuin-A, PTH/PTHrP, pyrophosphate, statins, and bisphosphonates. The
      precise mechanism of vascular calcification is of interest.

PMID- 16408511
TI  - [Genetics of centenarian].

PMID- 16408512
TI  - [Gastroenterological diseases in the aged].

PMID- 16408513
TI  - [A longitudinal study of cognitive function and the relationship between
      cognition and activities of daily living in the elderly].
AB  - AIM: To describe fundamental cognitive function and change in the elderly and
      examine interaction between cognition and ADL. METHODS: We investigated the
      mental and physical condition of 12,140 persons aged 65 years or over in 2000 and
      2002 according to the Eligibility Survey Questionnaire for Long-term Care
      Insurance. The percentage correct and correlation coefficients of six items in
      the Questionnaire concerning "Understanding" : "Understands daily activities",
      "Answers date of birth and age", "Remembers what the subject did before
      interview", "Says own name", "Knows what season it is now", "Knows the place
      where the subject is" were determined. The interaction between these six items
      and ADL were also examined. RESULTS: The percentage correct of "name" was .89,
      "date of birth and age" .78, "place" .75, "season" .66, "daily activities" .59,
      "Remembers before interview" .58. The item with high percentages of correct
      answer in 2000 higher tended to remain high in 2002. Those who were not impaired
      physically but unable to understand cognitive items tended to require
      significantly more support for ADL such as "Dressing and undressing", and
      "Personal hygiene", "Taking medication". CONCLUSION: The percentage correct of
      each item was considered to be associated with a classical model of memory
      process: encoding, retention and retrieval. It seemed to require the whole memory
      process to "Understand daily activities" and "Remember before interview", since
      the contents were changeable. On the other hand, "name" and "date of birth and
      age" were relatively well preserved, since these items were encoded and stored in
      the early stage of life and retrieved repeatedly. "Place" and "Season" were
      between these two groups.

PMID- 16408514
TI  - [Subjective well-being and all-cause mortality among middle-aged and elderly
      people living in an urban Japanese community].
AB  - AIM: We examined the relationship between subjective well-being and all-cause
      mortality among middle-aged and elderly people, using a population-based
      prospective approach (Tokyo Metropolitan Institute of Gerontology-Longitudinal
      Interdisciplinary Study on Aging). METHODS: The participants were 1,034 men and
      1,413 women aged 52 to 77 years, living in an urban Japanese community. The
      baseline data on age, gender, number of years of education, hospitalization,
      lifestyle-related illness, subjective health status, living alone and subjective
      well-being (measured by Philadelphia Geriatric Center Morale Scale) were
      collected in 1993. RESULTS: Mean subjective well-being scores for men and women
      were 12.3 +/- 3.2 and 11.9 +/- 3.5, respectively. Analysis of covariance
      controlling for age, the number of years of education, hospitalization, lifestyle
      related illness and living alone, revealed no inter-gender difference in
      subjective well-being. Multiple regression analysis to explore factors related to
      subjective well-being showed that age in men, and the number of years of
      education in both genders were significantly, independently and positively
      associated with subjective well-being, and that hospitalization, lifestyle
      related illness and living alone in both genders were significantly,
      independently and negatively related to subjective well-being. From 1993 to 2000,
      there were 183 deaths and 258 dropouts. In Cox's multivariate hazard model
      adjusted for age, the number of years of education, hospitalization, lifestyle
      related illness and living alone, there was a significant and independent
      association between a low level of subjective well-being and the risk for all
      cause mortality in both genders. CONCLUSION: Satisfaction with life is an
      important factor affecting longevity among middle-aged and elderly people.

PMID- 16408515
TI  - [Carotid parameters measured by ultrasonography as a marker of atherothrombotic
      infarction and lacunar infarction in high risk elderly people].
AB  - AIM: Many studies have reported that carotid parameters measured by
      ultrasonography were predictors for stroke. The aim of this study was to
      investigate by cross-sectional study in elderly people having cardiovascular risk
      factors whether those carotid parameters are markers for atherothrombotic
      infarction (AI) and lacunar infarction (LI). METHODS: Subjects of this study were
      314 patients aged 65 years or older who had controlled cardiovascular risk
      factors and assessed carotid artery by ultrasonography. Subjects were categorized
      into control, AI and LI group. Clinical characteristics (biochemical analysis,
      body mass index, systolic/diastolic blood pressure, smoking habits, hypertension,
      diabetes mellitus and statin therapy) and carotid parameters (maximum intima
      media thickness (Max-IMT), plaque score (PLQ-S) and Maximum pulsatility index
      (Max-PI)) were compared among three groups. RESULTS: PLQ-S, Max-PI, frequency of
      PLQ-S > or = 10mm and frequency of Max-PI > or = 2.0 in the AI group were
      significantly higher than in the control group. There were no significant
      differences between control and LI group concerning those carotid parameters.
      Multivariate logistic regression analysis showed that there were significant
      correlations between AI and PLQ-S > or = 10mm (odds ratio 2.980; P = 0.011), AI
      and Max-PI > or = 2.0 (odds ratio 2.458; P = 0.038), but there was no significant
      correlation between those carotid parameters and LI. CONCLUSION: This study
      suggests that in high risk elderly people, PLQ-S and PI are better markers for AI
      than IMT, but those carotid parameters have poor associations with LI.

PMID- 16408516
TI  - [The implications of skeletal muscle mass for health promotion in community
      dwelling elderly people].
AB  - AIM: The purpose of this study is to determine whether skeletal muscle mass
      measured by bioelectrical impedance analysis can be associated with health
      conditions for elderly men and women in the community. METHODS: This study
      described the characteristics of the appendicular and total skeletal muscle mass
      by sex and age. In addition, the relationship between muscle mass and usual
      walking speed, instrumental activities of daily living (IADL) and life-styles,
      diet and exercise of 394 elderly persons who use a community center and live in a
      metropolitan suburb was examined. RESULT: This study showed that both
      appendicular and total skeletal muscle mass decreases with age in both men and
      women, and that men have greater skeletal muscle mass than women in all age
      groups. Both appendicular and total skeletal muscle mass had a significant
      positive correlation with usual walking speed in men and women. Men with
      efficient IADL had greater skeletal muscle mass than those with inefficient IADL,
      while there was no significant difference for women. In men the skeletal muscle
      mass was related to efficiency in IADL and life-styles, diet and exercise.
      CONCLUSION: These findings may also suggest that the skeletal muscle mass can
      reflect health conditions in community-dwelling elderly persons in Japan.

PMID- 16408517
TI  - [A case of misinsertion of the PEG tube into the abdominal cavity recovered on a
      referral to the outpatient by using simple endoscopy techniques].
AB  - We report a case of a 53-year-old man, who had been bed-ridden due to the
      progression of spinocerebellar degeneration and had been relying on percutaneous
      endoscopic gastrostomy (PEG) feeding for long-term nutritional support at home.
      The patient was referred to our clinic from his local GP because of suspected
      misinsertion of the PEG tube into the abdominal cavity on regular exchange of the
      tube. We performed emergent gastric endoscopy. First we induced the biopsy
      forceps through an endoscopic fiber, and pulled the forceps out through the
      injured fistula to the surface. Then the loop wire used for PEG placement was
      inserted through the fistula to the stomach using the forceps. The PEG tube was
      then inserted per oral and replacement was completed according to the usual pull
      method. This procedure enabled the replaced PEG tube to cover the perforated site
      as well as to reduce intragastric pressure, thereby prevented the occurrence of
      panperitonitis, a common severe complication expected in case of perforated
      fistula, caused by the leakage of intragastric contents. The patient showed no
      signs of complications, and could continue to receive in-home care without being
      admitted to the hospital for acute care.

PMID- 16408518
TI  - [A case of corticobasal degeneration that progressed from primary progressive
      aphasia].
AB  - A 65-year-old woman began to experience slowly progressive speech disturbance
      from 2001. She was admitted to our hospital for examination on May 2003. She had
      dysprosody, paragraphia, and mild disturbance in comprehension of spoken
      language. Repetition was preserved. No clear paraphasia was found. Calculation
      was disturbed, but there were no other neurological abnormalities including
      apraxia and agnosia. Brain MRI showed atrophy of the left frontal and parietal
      lobes. 99mTc-ECD SPECT showed decreased blood flow in the left frontal lobe and
      parietal lobe, especially in the Broca area and supplemental motor cortex.
      Primary progressive aphasia was diagnosed, because aphasia lasted for 2 years
      without other neurological deficits, and her daily activity was well preserved.
      During follow up, facial apraxia appeared from December 2003, and limb apraxia
      appeared from May 2004, followed by rigidity predominantly in the right upper
      limb and dementia. She was diagnosed as having corticobasal degeneration (CBD).
      The second SPECT on December 2004 showed progression of the decrease in cerebral
      flow at the same area showed by the first SPECT. SPECT is useful examination to
      predict the progress of the disease because the decrease of blood flow was
      recognized before the progression to CBD.

PMID- 16408519
TI  - [Long-term prognosis of unilateral spatial neglect--dissociation between
      conventional tests and behavioral observation].
AB  - The long-term prognosis of unilateral spatial neglect (USN) in three elderly
      patients with stroke was investigated. Case 1 was a 62-year-old man who had
      suffered from right putaminal hemorrhage three years ago. Obvious right USN was
      found soon after the onset. After 6 months of rehabilitation he recovered and
      became independent in ADL without USN signs in daily circumstances. However, left
      USN signs appeared in some stressful situations such as traditional poetry-based
      competition or driving an electrical wheelchair on crowded roads. Case 2 was a 62
      year-old man who had suffered from cerebral hemorrhage in the right putamen 6
      years ago. He showed left USN soon after the onset, but it disappeared gradually.
      Cerebral infarction in the left basal ganglia occurred 6 years after the first
      attack. He showed decline of general attention accompanying left USN. Case 3 was
      a 70-year-old man who had showed left USN signs 7 years previously. He became
      independent and disappeared USN signs. However his activities of daily living
      declined gradually, and mental status became worse. Left USN signs were observed
      again on USN tests. Left USN was observed in three cases soon after the onset of
      the first stroke and then disappeared. However, USN signs became obvious in some
      specific situations. The appearance or disappearance of USN seemed to depend on
      the relationship among severity of USN, physical and mental functions, and
      circumstances in which USN was evaluated.

PMID- 16408520
TI  - Does psychoanalysis have a future? Yes.

PMID- 16408521
TI  - Does psychoanalysis have a future? No.

PMID- 16408522
TI  - Lay beliefs about treatments for people with mental illness and their
      implications for antistigma strategies.
AB  - OBJECTIVE: First, to describe factors influencing the public's attitude toward
      treatment recommendations for people with mental illness; second, to identify
      coherent belief systems about the helpfulness of specific interventions; and
      third, to discuss how to ameliorate mental health literacy and antistigma
      strategies. METHOD: Participants of a representative telephone survey in the
      general population (n = 1737) were presented with a vignette depicting a person
      with either schizophrenia or depression. From a list of suggestions, they were
      asked to recommend treatments for this person. We used a factor analysis to group
      these proposals and used the factors as the dependent variables in a multiple
      regression analysis. RESULTS: Treatment suggestions are summarized in 4 groups,
      each characterizing a specific therapeutic approach: 1) psychopharmacological
      proposals (that is, psychotropic drugs), 2) therapeutic counselling (from a
      psychologist or psychiatrist or psychotherapy), 3) alternative suggestions (such
      as homeopathy), and 4) social advice (for example, from a social worker). Medical
      treatments were proposed by people who had a higher education, who had a positive
      attitude toward psychopharmacology, who correctly recognized the person depicted
      in the vignette as being ill, who were presented with the schizophrenia vignette,
      who kept social distance, and who had contact with mentally ill people. The
      variables could explain alternative and social treatment proposals only to a
      small extent. CONCLUSIONS: The public's beliefs about treatment for people with
      mental illness are organized into 4 coherent systems, 2 of which involve evidence
      based treatments. Medical treatment proposals are influenced by adequate mental
      health literacy; however, they are also linked to more social distance toward
      people with mental illness. Additionally, efforts to better explain nonmedical
      treatment suggestions are needed. Implications for further antistigma strategies
      are discussed.

PMID- 16408523
TI  - Mental health service use in a nationally representative Canadian survey.
AB  - BACKGROUND: Previous Canadian surveys have noted a wide range of prevalence rates
      for mental health service use and found no consistent relation between type of
      contact with mental health professionals and severity of illness. This study is
      the first investigation to examine the prevalence and correlates of mental health
      service use in a nationally representative Canadian survey. METHODS: The Canadian
      Community Health Survey Cycle 1.1 was conducted between 2000 and 2001 (n =
      125,493; respondent age 12 years and over; response rate; 84.7%). Respondents
      were asked whether they had contacted a professional because of emotional
      symptoms in the past year and about their experience of barriers to treatment.
      DSM-IV major depression and alcohol dependence diagnoses were assessed with the
      Composite International Diagnostic Interview Short Form. The relation between a
      range of measures of clinical severity and the type of professional contacted for
      emotional symptoms was examined. RESULTS: The prevalence of 12-month help seeking
      for emotional symptoms was 8.3% (99%CI, 8.10 to 8.55); an additional 0.6% (99%CI,
      0.49 to 0.62) of the sample perceived a need for treatment without seeking care.
      Respondents endorsing contact with multiple professionals or with psychiatrists
      only had higher levels of severity than those who had contact with family doctors
      only or nonphysician professionals only. CONCLUSIONS: Although untreated
      depression remains a significant problem in Canada, more severe illness was more
      likely to be associated with seeing a psychiatrist (or multiple professionals),
      indicating a relation between greater severity of mental illness and receiving
      more specialized care.

PMID- 16408524
TI  - Suicide attempts and associated factors in Newfoundland and Labrador, 1998-2000.
AB  - OBJECTIVE: This study examined the epidemiology and associated factors for
      suicide attempts requiring hospitalization in the province of Newfoundland and
      Labrador. METHOD: We extracted data from the provincial hospital separation
      database. Outcome measures included incidence rates (IRs) of suicide attempts by
      age, sex, and geographical region of residence. We also analyzed sociodemographic
      data to determine associated factors. RESULTS: A total of 978 patients who were
      hospitalized owing to suicide attempts were identified for 1998-2000, giving an
      overall IR of 68.7 per 100,000 person-years (P-Y). The age-specific rate for
      people aged 15 to 19 years was much greater, at 143.0 per 100,000 P-Y. The
      overall female-to-male ratio was 1.3, with an attempted suicide rate of 76.1 per
      100,000 P-Y for female patients and 60.3 per 100,000 P-Y for male patients (P =
      0.001). Labrador (210.2 per 100,000 P-Y), a region with a high Aboriginal
      population, had a higher rate of suicide attempts, compared with the island
      portion of the province (59.0 per 100,000 P-Y) (P < 0.001). More than 70% of
      hospitalizations were associated with psychiatric diagnosis. Poisoning was the
      most frequent method of attempting suicide. Higher IRs of suicide attempts were
      found among people who were divorced or separated and among those who were less
      educated (P < 0.001). CONCLUSIONS: Suicide attempt represents a significant
      public health concern in the province, particularly in Labrador. An increased
      risk of suicide attempts was associated with single status, female sex, younger
      age (teen or young adult), and low educational level during the index attempt.
      Further research is needed to explicate these findings and increase our
      understanding of attempted suicide.

PMID- 16408525
TI  - Psychosocial and clinical predictors of symptom persistence vs remission in major
      depressive disorder.
AB  - OBJECTIVE: The present study evaluates the impact of a range of psychosocial
      factors on the outcome of major depression while controlling for the effect of
      clinical variables. METHOD: Patients (n = 171) seen in consultation at a mood
      disorders clinic completed measures of neuroticism, rumination, coping style,
      sexual abuse history, and parental bonding experiences at Time 1 and completed
      measures of interpersonal and achievement life events and depression 12 months
      later. RESULTS: In univariate analyses, neuroticism, rumination, interpersonal
      and achievement life events, and sexual abuse history were associated with
      nonremission, whereas avoidance coping was associated with remission at Time 2.
      Interpersonal and achievement life events and sexual abuse history were
      associated with nonimprovement, whereas avoidance coping was associated with
      improvement at Time 2. Significant predictors of both remission and improvement
      in logistic regression analyses controlling for clinical variables (depression
      and anxiety severity, duration of illness, and age) included avoidance,
      interpersonal life events, and the interaction between avoidance and
      interpersonal life events. CONCLUSIONS: Interpersonal events and responses to
      depression (that is, coping) play an important role in the outcome of major
      depression. Further attention to coping style and interactions between
      psychological factors and life events is warranted in future research on
      depression persistence.

PMID- 16408526
TI  - The relation between childhood adverse experiences and disability due to mental
      health problems in a community sample of women.
AB  - OBJECTIVE: The objective of this study was to examine the association between
      selected childhood adverse experiences and disability due to mental health
      problems in a community sample of women. Variables of interest included childhood
      physical and sexual abuse, parental psychiatric and substance abuse history, and
      sociodemographic factors. METHOD: Girls and women (aged 15 to 64 years) from a
      province-wide community sample (n = 4239) were asked about disability and most
      childhood adverse experiences through interview; a self-administered
      questionnaire inquired about child abuse. Logistic regression (crude and adjusted
      odds ratios) was used to test the associations between childhood adversity and
      disability due to mental health problems. RESULTS: Approximately 3% of the women
      had a disability due to mental health problems. Among women with a disability,
      about 50% had been abused while growing up. After controlling for income and age,
      we found that disability showed the strongest association with childhood sexual
      abuse, physical abuse, and parental psychiatric disorder. CONCLUSION: Disability
      due to mental health problems was experienced by women with and without exposure
      to abuse in childhood. However, childhood sexual abuse and physical abuse were
      important correlates of disability. Disability creates suffering and loss for the
      individual and society; this issue merits more research in relation to child
      abuse.

PMID- 16408527
TI  - Construct validity of an instrument to assess major depression in parents in
      epidemiologic studies.
AB  - OBJECTIVE: The Longitudinal Study of Child Development in Quebec (LSCDQ) is a
      community study of children that examines the risk factors, such as parental
      depression, linked to childhood psychopathology and maladaptive functioning. Our
      goal was to test the construct validity of an instrument to assess major
      depression in the parents. METHOD: Parents of a representative sample of 2120
      infants born in the province of Quebec in 1998 were selected. The major
      depression instrument was administered to the parents when the infants were aged
      29 months. We tested the construct validity of the instrument by examining 1) sex
      differences in symptoms and prevalence, 2) the rank order of the prevalence of
      symptoms, 3) the clustering of symptoms, and 4) the association of depression
      with functional impairment and treatment-seeking behaviour. RESULTS: Depression
      was twice as common in mothers as in fathers. Most mothers and fathers who
      reported ever being depressed for 2 or more weeks had also experienced at least 4
      additional depression symptoms. The rank order of symptom prevalence was
      comparable to that found in other studies. At least 50% of parents reported
      having talked to a professional and that suffering from depression had interfered
      with their functioning. CONCLUSIONS: The expected sex differences, the rank order
      of symptom prevalence, the symptom clustering, and the associations with
      functional impairment and treatment-seeking behaviour support the construct
      validity of a brief questionnaire on parental major depression.

PMID- 16408528
TI  - [Standardized and clinical evaluation of defense mechanisms: a critical review of
      6 quantitative tools].
AB  - BACKGROUND: The defense mechanisms (DM) concept goes back to the foundation of
      psychoanalysis and is one of its theoretical cornerstones. Recently, with the
      introduction of this notion in an experimental item of categorical
      classification, DMs have become a new field in research and scientific
      communication. The increasing number of studies taking DMs into account matches
      the development of clinical evaluation scales that are easier to use than
      projective tests. To our knowledge, there is no comparative analysis of these
      tools. OBJECTIVE: We aimed first to describe the operating mode and metrological
      qualities of the most recent scales and then to highlight the benefits and
      limitations of these clinical evaluation tools. Finally, this article aims to
      help clinicians choose a tool that is most convenient for their protocol. METHOD:
      We introduce the following tools through a literature review: Defense Mechanism
      Inventory, Defense Mechanism Profile, Defense Style Questionnaire (DSQ), Defense
      Mechanism Rating Scale, Life Style Index, and Response Evaluation Measure.
      CONCLUSION: Using clinical scales includes many limitations associated with the
      DM concept. Nevertheless, their feasibility and validity warrant their use. The
      DSQ stands out for its many qualities, but the other tools specificities are yet
      to be considered in regard to the chosen protocols.

PMID- 16408529
TI  - The child behavior checklist together with the ADHD rating scale can diagnose
      ADHD in Korean community-based samples.
AB  - OBJECTIVE: The purpose of this study was to examine the clinical validities and
      efficiencies of the Child Behavior Checklist (CBCL) and the ADHD Rating Scale-IV
      (ARS) in identifying children with attention-deficit hyperactivity disorder
      (ADHD) in Korean community-based samples. METHOD: A large sample of elementary
      school students (n = 1668) participated in this study. We used the CBCL and the
      ARS as the screening instruments. Diagnoses were determined by clinical
      psychiatric interviews and confirmed by DSM-IV-based structured interviews.
      RESULTS: Of the 46 subjects who underwent clinical psychiatric interviews, 33
      were diagnosed as having ADHD. A T score of 60 with regard to the Attention
      Problems profile of the CBCL resulted in a reasonable level of sensitivity or
      positive predictive value in the diagnosis of ADHD. In both the parent and
      teacher reports of the ARS, 90th percentile cut-off points resulted in a high
      level of predictive value. The highest levels of specificity and positive
      predictive value were obtained when we combined the CBCL (T > or = 60 in
      Attention Problems) and the ARS (parent-teacher total > or = 90th percentile)
      reports. CONCLUSIONS: These findings suggest that the combined use of the CBCL
      and the ARS could serve as a rapid and useful clinical method of predicting or
      even diagnosing children with ADHD in epidemiologic case definitions.

PMID- 16408530
TI  - Re: the persistence of folly: a critical examination of dissociative identity
      disorder.

PMID- 16408531
TI  - Re: the persistence of folly: a critical examination of dissociative identity
      disorder. What are Dr Piper and Dr Merskey trying to do?

PMID- 16408532
TI  - Re: the persistence of folly: a critical examination of dissociative identity
      disorder.

PMID- 16408533
TI  - Safety culture and crisis resource management in airway management: general
      principles to enhance patient safety in critical airway situations.
AB  - Airway management is a cornerstone of patient safety in anaesthesiology and in
      emergency and critical care medicine. Deficiencies in airway management could
      have catastrophic results for the patient. In anaesthesia patients, in
      particular, a high level of safety should be expected. It has been proven in
      other high-risk and complex industrial fields that obtaining very high levels of
      safety requires special strategies and safety philosophies in order to guarantee
      long-term low-risk production. The concept of safety culture has invaded many
      industries, more recently including medicine. Concepts of the high reliability
      organizations (HROs) are now ready to be adapted to medicine and offer promising
      improvements in health care. This paper applies some of the HRO principles to
      airway management and illustrates how to transform more general strategies to
      practical application in the clinical world. This includes the use of key
      elements of crisis resource management (CRM) and the development of a checklist
      for safety in airway management.

PMID- 16408534
TI  - Evaluation of the airway and preparation for difficulty.
AB  - Preoperative airway evaluation is essential to consider which is the best method
      of maintaining and protecting the airway during surgery and whether problems with
      airway management are likely. In general surgical patients, the prevalence of
      difficult intubation is low and tests have poor predictive power. This means that
      the patient may be evaluated as normal but prove to be difficult. The absence of
      reliable prediction in general surgical patients means that airway strategy holds
      the key to successful management. Where there are obvious abnormalities in the
      history, examination or imaging the preoperative evaluation will allow choice of
      the most appropriate airway strategy which may include preparation of the
      patient, assembling of alternative airway equipment, advice and help from a more
      senior or skilled anaesthetist or aid from a surgical colleague or assistant.

PMID- 16408535
TI  - Supraglottic airway devices.
AB  - Supraglottic airway devices are developed with increasing frequency following the
      overwhelming success of the laryngeal mask airway (LMA). Currently, the LMA, the
      ProSeal laryngeal mask airway (PLMA), the laryngeal tube (LT), the laryngeal tube
      with integrated suctioning tube (LTS) and the oesophageal tracheal combitube
      (OTC) are the best evaluated and most widespread devices. Both the LMA and the
      PLMA have been shown to be perfectly suitable for routine anaesthesia and
      emergency airway management. While the LMA is limited by the lack of reliable
      protection against aspiration, the value of the PLMA in this respect remains
      undetermined yet. LT and LTS are primarily intended as emergency airway devices,
      but have also been successfully used during controlled ventilation in adults. The
      OTC, though advocated for emergency as well as routine use, is limited by high
      airway morbidity and possible serious complications.

PMID- 16408536
TI  - Infraglottic airway devices and techniques.
AB  - Airway management involves far more than just proficiency with tracheal
      intubation techniques. There are several infraglottic techniques available and
      the method chosen will depend on the accessibility of equipment, the level of
      training and expertise, and the patient's specific injury or disease.
      Endotracheal intubation is most commonly performed by direct laryngoscopy.
      Several modifications of laryngoscope blades and a variety of adjuncts such as
      bougies may help to accomplish even a difficult airway. Rigid intubation
      fibrescopes do improve the view of the larynx, especially in patients with
      difficult anatomy. They also permit tracheal intubation with less head and
      cervical spine movement than is often generated by direct laryngoscopy.
      Successful intubation, however, requires considerable experience, as in
      intubation techniques using flexible fibrescopes. Both the EasyTube and the
      Combitube serve as an infraglottic or a supraglottic airway. The tip of the
      EasyTube resembles the one of an endotracheal tube, whereas the Combitube is much
      more bulky.

PMID- 16408537
TI  - Fiberoptic techniques.
AB  - Fiberoptic intubation of the spontaneously breathing patient is the gold standard
      and technique of choice for the elective management of a difficult airway. In the
      hands of the properly trained and experienced user, it is also an excellent 'plan
      B' alternative when direct laryngoscopy unexpectedly fails. Fiberscope-assisted
      intubation through an endoscopy face mask, laryngeal mask airway or intubating
      laryngeal mask airway secures ventilation and oxygenation, and permits
      endotracheal intubation in airway emergency situations. Portable fiberscopes can
      be used in remote settings, increasing patient safety. This review discusses
      current fiberoptic intubation techniques and their applications in the management
      of both the anticipated and unanticipated difficult airway.

PMID- 16408538
TI  - Surgical approach in difficult airway management.
AB  - In all difficult airway algorithms, cricothyroidotomy is the life-saving
      procedure and is the final 'cannot ventilate, cannot intubate' option, whether in
      pre-hospital, emergency department, intensive care unit, or operating room
      patients. Cricothyroidotomy is a relatively safe and rapid means of securing an
      emergency airway. As with all other critical procedures in emergency medicine, a
      thorough knowledge of the technique and adequate practice prior to attempting to
      perform an emergency cricothyroidotomy are essential.

PMID- 16408539
TI  - Complications of managing the airway.
AB  - The inability to secure the airway, with consequent failure of oxygenation and
      ventilation, is a life-threatening complication. Failure of oxygenation leads to
      hypoxia followed by brain damage, cardiovascular dysfunction, and finally death.
      Time is a very crucial factor in this context. Complications vary widely in
      severity; while some are dramatic and immediately life-threatening (unrecognized
      esophageal intubation), others can be severe and long-lasting (nerve injuries) or
      mild and short-lived (sore throat). To minimize injury to the patient, the
      anesthesiologist should examine the patient's airway carefully, identify any
      potential problems, devise a plan that involves the least risk for injury, and
      have a back-up plan immediately available. Each anesthesiology department should
      establish guidelines/algorithms specific to their institution. Unfortunately, a
      reliable test for detecting all patients at risk does not exist.

PMID- 16408540
TI  - Strategies and algorithms for management of the difficult airway.
AB  - Management of the difficult airway is the most important patient safety issue in
      the practice of anaesthesia. Many national societies have developed algorithms
      and guidelines for management of the difficult airway. The key issues of this
      chapter are definition of terms, the advantages and disadvantages of the use of
      guidelines, and a comparison of different algorithms and guidelines for
      management of the most important clinical airway scenarios. Although there is no
      strong evidence of benefit for any specific strategy or algorithm for management
      of the difficult airway, there is strong agreement that a pre-planned strategy
      may lead to improved outcome.

PMID- 16408541
TI  - Airway management in infants and children.
AB  - Anaesthesiologists, paediatricians, paediatric intensivists and emergency
      physicians are routinely challenged with airway management in children and
      infants. There are important differences from adult airway management as a result
      of specific features of paediatric anatomy and physiology, which are more
      relevant the younger the child. In addition, a number of inherited and acquired
      pathological syndromes have significant impact on airway management in this age
      group. Several new devices--e.g. different types of laryngeal mask airways in
      various sizes, small fibre-endoscopes--have been introduced into clinical
      practice with the intention of improving airway management in this age group.
      Important new studies have gathered evidence about risks and benefits of certain
      confounding variables for airway problems and specific techniques for solving
      them. Airway-related morbidity and mortality in children and infants during the
      perioperative period are still high, and only a thorough risk determination prior
      to and continuous attention during the procedure can reduce these risks.
      Appropriate preparation of the available equipment and frequent training in
      management algorithms for all personnel involved appear to be very important.

PMID- 16408542
TI  - Airway management in emergency situations.
AB  - Securing and monitoring the airway are among the key requirements of appropriate
      therapy in emergency patients. Failures to secure the airways can drastically
      increase morbidity and mortality of patients within a very short time. Therefore,
      the entire range of measures needed to secure the airway in an emergency, without
      intermediate ventilation and oxygenation, is limited to 30-40 seconds.
      Endotracheal intubation is often called the 'gold standard' for airway management
      in an emergency, but multiple failed intubation attempts do not result in
      maintaining oxygenation; instead, they endanger the patient by prolonging hypoxia
      and causing additional trauma to the upper airways. Thus, knowledge and
      availability of alternative procedures are also essential in every emergency
      setting. Given the great variety of techniques available, it is important to
      establish a well-planned, methodical protocol within the framework of an
      algorithm. This not only facilitates the preparation of equipment and the
      training of personnel, it also ensures efficient decision-making under time
      pressure. Most anaesthesia-related deaths are due to hypoxaemia when difficulty
      in securing the airway is encountered, especially in obstetrics during induction
      of anaesthesia for caesarean delivery. The most commonly occurring adverse
      respiratory events are failure to intubate, failure to recognize oesophageal
      intubation, and failure to ventilate. Thus, it is essential that every
      anaesthesiologist working on the labour and delivery ward is comfortable with the
      algorithm for the management of failed intubation. The algorithm for emergency
      airway management describing the sequence of various procedures has to be adapted
      to internal standards and to techniques that are available.

PMID- 16408544
TI  - Surgical training and duty-hour limits: an oxymoron or an idea whose time has
      come?

PMID- 16408543
TI  - Education and training in airway management.
AB  - Despite the use of alternative training methods and efforts to structure
      training, it remains a challenge to ensure that every anaesthesia trainee gains
      sufficient experience in the use of core techniques of airway management. As less
      time is spent in the operating room during training, it becomes less likely that
      trainees will be exposed to an adequate number of challenging airway cases that
      enable them to practise advanced techniques of airway management under
      supervision. Nowadays the only way to overcome this deficit in anaesthesia
      training is to prepare trainees as well as possible outside the operating room so
      that clinical training opportunities can be used most effectively when they
      arise. Sufficient training can only be ensured when the required equipment and
      time are provided. Therefore, particularly in the light of increasing economic
      pressures, it is necessary to address the responsibilities of everyone involved
      in the training process. Here, we critically review traditional and recent
      modalities of anaesthesia training, assess their value, and describe a multi
      modal approach to airway management education.

PMID- 16408545
TI  - Facial nerve neuroma.

PMID- 16408546
TI  - A pneumatized uncinate process causing obstruction.

PMID- 16408548
TI  - Cholesteatoma of the maxillary sinus.

PMID- 16408547
TI  - Vocal fold hemorrhage.

PMID- 16408549
TI  - A woman with a 42-year history of Meniere's syndrome.

PMID- 16408550
TI  - Mucoepidermoid carcinoma.

PMID- 16408551
TI  - Epithelial-myoepithelial carcinoma.

PMID- 16408552
TI  - Esophageal candidiasis.

PMID- 16408554
TI  - Researching supply reimbursement.

PMID- 16408553
TI  - Differentiating between squamous cell carcinoma and pigmented squamous cell
      carcinoma.

PMID- 16408555
TI  - Preoperative computed tomography may fail to detect patients at risk for
      perilymph gusher.
AB  - Perilymph gusher (PG) is a very rare occurrence that can lead to an adverse
      outcome during inner ear surgery. In the absence of a family history of X-linked
      mixed deafness syndrome, surgeons may have difficulty determining if a patient is
      at risk preoperatively. Radiographic imaging is often performed in an attempt to
      identify such a possibility, but there are few data to support the value of
      negative studies. We conducted a retrospective study of 3 cases of PG in which
      findings on preoperative high-resolution computed tomography (CT) of the temporal
      bone had been interpreted as normal. We reviewed these CTs to discern if they did
      in fact demonstrate any abnormalities that might have indicated a risk of PG, and
      we found that the original radiologist had missed a dilated internal auditory
      canal and a deformity of the cochlear modiolus in the affected ear of 1 of these
      patients. No abnormality was detected on review of the CTs of the other 2
      patients. Therefore, we conclude that negative CT findings do not necessarily
      rule out a risk of PG.

PMID- 16408556
TI  - Intraoperative use of mitomycin C in fibrous atresia of the external auditory
      canal.
AB  - The ability of mitomycin C to inhibit fibroblasts in vitro has prompted its use
      during standard surgical procedures as a means of preventing the development of
      adhesions and stenosis. We conducted a prospective study to evaluate the
      effectiveness of topical mitomycin C in maintaining an open external auditory
      canal in 6 ears of 4 patients with aural fibrotic atresia who were undergoing
      meatoplasty. During the procedure, we applied 1 ml of mitomycin C (0.4 mg/ml) for
      4 minutes to the external auditory canal (in 1 case, mitomycin C was reapplied to
      an ear 1 month later). Between 3 and 14 months postoperatively, the patency of
      the ear canal was assessed visually and hearing was evaluated audiometrically.
      Adequate patency was achieved in 5 of the 6 ears (83.3%), and the air-bone gap in
      these 5 ears had improved to 10 dB or less. No postoperative complications or
      sensorineural hearing loss was observed. In this very limited number of cases, we
      found that the intraoperative use of mitomycin C appeared to have been helpful in
      preventing scarring in both congenital and secondary fibrotic atresias of the
      external auditory canal. These preliminary results are encouraging, and a
      prospective, placebo-controlled study appears to be warranted.

PMID- 16408557
TI  - Rhabdomyosarcoma of the middle ear and mastoid: a case report and review of the
      literature.
AB  - We report a case of rhabdomyosarcoma of the middle ear and mastoid in a 3-year
      old boy. The patient was treated according to Intergroup Rhabdomyosarcoma Study
      IV protocol (chemo- and radiotherapy), and he experienced a complete remission.
      However 7 months after the completion of treatment, he experienced a recurrence
      at the primary site that spread to the brain. Despite treatment, the patient died
      of progressive metastasis to the lung 4 months later.

PMID- 16408558
TI  - Minimally invasive transoral catheter-assisted drainage of a danger-space
      infection.
AB  - We report the case of a 3-year-old boy who was brought to the emergency
      department for evaluation of a prolonged upper respiratory infection and
      diminished neck movement. Computed tomography identified a unilocular abscess
      extending from the level of C2 inferiorly to the diaphragm at the level of the T9
      vertebral body. We successfully treated this transcervical, transthoracic
      infection surgically via a transoral approach to the retropharyngeal abscess
      combined with catheter drainage and irrigation of the abscess cavity at a depth
      of 13 cm. At 25 months of follow-up, the patient exhibited no evidence of
      recurrent disease or postsurgical complications. In this article, we describe our
      minimally invasive technique for managing unusual deep-space neck infections in
      children.

PMID- 16408559
TI  - An alternative to a postnasal pack for the arrest of perioperative hemorrhage
      following curettage adenoidectomy.
AB  - Controlling bleeding with standard postnasal packing following curettage
      adenoidectomy is only occasionally warranted. Children find the packing
      experience unpleasant, and removal of the packing usually requires general
      anesthesia. We describe a simple technique for packing the nasopharynx with
      bilateral nasal tampons via an anterior approach. The tampons are much easier to
      insert than standard packing, they are well tolerated while in place, and they
      can be easily removed with perhaps only some light sedation rather than general
      anesthesia.

PMID- 16408560
TI  - Bilateral pleomorphic adenoma of the anterior tongue: a case report.
AB  - We report a case of bilateral pleomorphic adenoma of the anterior two-thirds of
      the tongue in a 38-year-old man. Both tumors were excised via a transoral route.
      To the best of our knowledge, this is the first reported case of a bilateral
      pleomorphic adenoma of the anterior tongue.

PMID- 16408561
TI  - Bilateral peritonsillar abscess revisited.
AB  - Bilateral peritonsillar abscess is uncommon. When it does occur; patients usually
      present with sore throat; other clinical signs and symptoms may differ from those
      usually associated with unilateral peritonsillar abscess. We describe 2 cases of
      bilateral peritonsillar abscess that were successfully treated with needle
      aspiration of both sides with a 14-gauge intravenous cannula. Needle aspiration
      is an accepted form of treatment for unilateral peritonsillar abscess, but to the
      best of our knowledge, its use as a sole treatment modality (with observation
      under intravenous antibiotic coverage) for bilateral peritonsillar abscess has
      not been previously reported in the literature. We also believe that the
      incidence of acute bilateral peritonsillar abscess may be higher than the rates
      that have been reported in the literature. Finally, we recommend that the
      threshold for imaging be low for any patient who is suspected of having acute
      bilateral peritonsillar abscess to avoid any delay in diagnosis and treatment.

PMID- 16408562
TI  - Polymorphous low-grade adenocarcinoma at the base of the tongue: an unusual
      location.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) is a malignant neoplasm of low
      aggressiveness that occurs almost exclusively in the minor salivary glands,
      primarily those in the palate. We report a case of PLGA that arose in the base of
      the tongue and subsequently metastasized to the neck. The tumor was resected
      through the oral cavity with wide margins and dissection. The neck metastasis was
      treated with radical neck dissection and radiotherapy. The patient recovered and
      remained disease-free at follow-up 30 months later. This case shows that PLGA,
      which has a variable morphologic appearance, can occur at sites other than the
      salivary glands.

PMID- 16408563
TI  - Pneumosinus dilatans frontalis: a case report.
AB  - Deformity of the forehead is usually the first clinical presentation of the
      abnormally large frontal sinus caused by pneumosinus dilatans. We report the
      diagnosis and surgical treatment of a case. The type of osteotomy we describe is
      recommended as a method of surgical treatment for this condition when the
      aesthetic problem is the major complaint.

PMID- 16408564
TI  - Falling sensation after the Epley maneuver.

PMID- 16408565
TI  - Teamwork between otologists and audiologists.

PMID- 16408566
TI  - Neurologists and the numbers.

PMID- 16408567
TI  - The pursuit of excellence in acute stroke care.

PMID- 16408568
TI  - Hypertension and stroke: 2005 Canadian Hypertension Educational Program
      recommendations.
AB  - BACKGROUND: Hypertension is the most important modifiable cause of stroke. The
      Canadian Hypertension Educational Program, representing Canada's experts in the
      field of hypertension, publishes annual evidence-based recommendations on the
      diagnosis and treatment of hypertension. METHODS: We present the 2005 Canadian
      Hypertension Educational Program guidelines regarding the management of
      hypertension in patients with stroke. RESULTS: The diagnosis of hypertension
      should be expedited and can be made as early as the second visit in patients with
      stroke. Unless contraindicated, a combination of angiotensin-converting-enzyme
      (ACE) inhibitors and diuretics is the preferred therapy in these patients. A
      target blood pressure below 140/90 mmHg for non-diabetic patients, below 130
      mmHg/80 mmHg for diabetic patients and below 125 mmHg/75 mmHg for those with
      renal disease and proteinuria (> 1 gram per day) should be reached. Lifestyle
      interventions may be as effective as medication and should be used in conjunction
      with medical management. Waist circumference should be less than 102 cm for men
      and 88 cm for women. There remains uncertainty about the management of high blood
      pressure in the context of acute stroke. CONCLUSIONS: A combination of ACE
      inhibitors and diuretics is recommended in hypertensive stroke patients. Blood
      pressure should be maintained below 140/90 mmHg.

PMID- 16408569
TI  - The epileptic encephalopathies of infancy and childhood.
AB  - The epileptic encephalopathies comprise a group of devastating seizure syndromes
      which begin in infancy and early childhood and usually result in intractable
      epilepsy. While some syndromes are relatively easily diagnosed early in their
      course, others take time to evolve, hampering an early, confident diagnosis.
      Epileptic encephalopathies are associated with slowing of cognitive function and
      evolution of severe behavioral disorders, which are often more distressing to
      families than the epilepsy. While an underlying etiology may explain some of this
      co-morbidity, many children have no identifiable etiology found for their
      seizures. In these "idiopathic" cases, recurrent subtle seizures, frequent
      epileptiform discharge and non-convulsive status epilepticus probably all play a
      role in deterioration of cognitive function and evolution of behavior disorders.
      This paper will review the most common epileptic encephalopathy syndromes,
      discuss the cognitive and behavioral co-morbidities and review current
      therapeutic options.

PMID- 16408570
TI  - Progress in clinical neurosciences: measuring the benefit of therapies for
      neurological disorders.
AB  - BACKGROUND: Clinicians in the neurosciences need to interpret and apply a growing
      body of evidence about therapy. METHODS: Using a clinical scenario about painful
      diabetic neuropathy and evidence about one treatment option, we review the
      advantages, limitations, and the clinical interpretation of commonly reported
      measures of effectiveness, emphasizing their application to the care of
      individual patients. RESULTS: Absolute differences between treatment and control
      groups (e.g., absolute risk difference) are clinically intuitive and preferable
      to relative measures (e.g., relative risk). The number needed to treat is
      particularly useful and clinically applicable. Continuous measures are best
      interpreted using thresholds of clinically important change, which provide
      information about the number of patients experiencing meaningful improvement or
      worsening. CONCLUSIONS: Using simple principles of evidence based care,
      clinicians can correctly interpret the common measures of treatment effectiveness
      and apply them to the care of individual patients.

PMID- 16408571
TI  - Highlights of the 2002 Canadian Neurological Society (CNS) manpower survey.
AB  - BACKGROUND: The Canadian Neurological Society commissioned a manpower survey in
      2002 to assess demographics, distribution, specialty interests, working
      conditions, job satisfaction and future plans of neurologists across the country.
      METHODS: A survey was mailed to all known Canadian neurologists (n = 694) on two
      separate occasions. Further encouragement by telephone contact was undertaken.
      The response rate was 54%. RESULTS: The mean age of neurologists who responded
      was 51 years, with 14% being women. Approximately 55% of neurologists were
      community-based. Seventy-six percent designated a sub-specialty interest. On
      average, neurologists worked 57 hours per week and the majority had significant
      "on-call" commitments. Job satisfaction was higher among academic neurologists
      when compared with community-based neurologists, and greater among men than
      women. A greater percentage of older neurologists were satisfied with their work
      than their younger colleagues. Significant attrition in the neurological work
      force is a major concern, since up to 20% of neurologists reported that they are
      likely to retire in the next five years and about 15% are likely to reduce their
      practice. CONCLUSIONS: This survey suggests that substantial concerns are facing
      Canadian neurology over the next five years. Major efforts to retain existing
      expertise and enhance residency training will be required to simply maintain the
      present quality of neurological care in Canada.

PMID- 16408572
TI  - TPA use for stroke in the Registry of the Canadian Stroke Network.
AB  - BACKGROUND: Thrombolytic therapy with recombinant tissue plasminogen activator
      (tPA) has been shown to be cost-effective and safe. Thrombolysis for stroke with
      tPA is now a standard of care in North America. However, it is only used on a
      small percentage of patients. METHODS: The Registry of the Canadian Stroke
      Network was a consent-based stroke registry from 21 hospital sites across Canada.
      Using the thrombolysis data in phase 1 and 2 of the Registry, we sought to
      describe the use of stroke thrombolysis and its outcomes. RESULTS: A total of
      4107 patients were diagnosed with ischemic stroke in phase 1 and 2 of the
      Registry, of which 8.9% were treated with tPA. In consented tPA patients, the
      method of tPA administration was 85.8% i.v. only, 9.0% ia only, and 5.2%
      i.v./i.a. combined. Patients had a median onset-to-treatment time of 167 minutes
      [IQR 140-188]. One quarter (25.5%) of eligible candidates (time from onset <150
      minutes) were treated with tPA. Protocol violations occurred in 27.7% (67/242) of
      patients with 14.9% (10/67) mortality. Overall, in-hospital mortality was 11.6%.
      Lower Canadian Neurological Scale score and higher glucose level were predictive
      of mortality The symptomatic intracerebral hemorrhage (ICH) rate (phase 2 only)
      was 4.3%. The mean Stroke Impact Scale-16 score at six months was 73.2,
      approximately equivalent to a modified Rankin scale score of 2. CONCLUSIONS: At
      selected hospitals in Canada, thrombolysis use is higher than previously reported
      rates. Thrombolysis continues to be safe and effective in Canada.

PMID- 16408573
TI  - The numbers needed to treat for neurological disorders.
AB  - BACKGROUND: Numerous therapeutic interventions have been developed in the
      neurosciences. Clinicians need summary measures about efficacy of therapies that
      derive from the best available evidence, and that can be readily extrapolated to
      clinical practice. The number needed to treat (NNT) is intuitive and clinically
      applicable. We provide clinicians with a single source that summarizes important
      therapies in the main neurological and neurosurgical areas. METHODS: Critically
      appraised evidence about therapies in the neurosciences was obtained from meta
      analyses in all neurosciences groups in the Cochrane library, and from critically
      appraised topics at the University of Western Ontario. Therapies were included if
      they were deemed relevant and if outcomes were dichotomous. For each therapy, we
      obtained absolute risk differences and their 95% confidence intervals (CI), the
      corresponding NNTs, control and experimental event rates, and the time-frame of
      the outcome assessment. RESULTS: We assembled a table of NNTs for 87
      interventions in ten disease categories, deriving from meta-analyses (70%) or
      randomized controlled trials (30%), and assessing surgical interventions (7%),
      procedures (9%) or pharmacological treatments (84%). The NNTs varied widely,
      ranging from 1 in the use of epidural blood patch for post-dural puncture
      headache to 4608 for meningococcal vaccination. Preventative interventions had
      substantially larger NNTs. Time-frames were inappropriately short for many
      chronic conditions. CONCLUSIONS: Large collections of NNTs provide useful,
      updateable summaries of therapeutic effects in the neurosciences, an increasingly
      interventional clinical field.

PMID- 16408574
TI  - Adult onset spinocerebellar ataxia in a Canadian movement disorders clinic.
AB  - BACKGROUND: The spinocerebellar ataxias (SCAs) are a genetically and clinically
      heterogeneous group of neurodegenerative disorders. Relative frequencies vary
      within different ethnic groups and geographical locations. OBJECTIVES: 1) To
      determine the frequencies of hereditary and sporadic adult onset SCAs in the
      Movement Disorders population; 2) to assess if the fragile X mental retardation
      gene 1 (FMR1) premutation is found in this population. METHODS: A retrospective
      chart review of individuals with a diagnosis of adult onset SCA was carried out.
      Testing for SCA types 1, 2, 3, 6, 7, and 8, Dentatorubral-pallidoluysian atrophy
      (DRPLA), Friedreich ataxia and the FMR1 expansion was performed. RESULTS: A total
      of 69 patients in 60 families were identified. Twenty-one (35%) of the families
      displayed autosomal dominant and two (3.3%) showed autosomal recessive (AR)
      pattern of inheritance. A positive but undefined family history was noted in nine
      (15%). The disorder appeared sporadic in 26 patients (43.3%). In the AD families,
      the most common mutation was SCA3 (23.8%) followed by SCA2 (14.3%) and SCA6
      (14.3%). The SCA1 and SCA8 were each identified in 4.8%. FA was found in a
      pseudodominant pedigree, and one autosomal recessive pedigree. One sporadic
      patient had a positive test (SCA3).Dentatorubral-pallidoluysian atrophy and FMR1
      testing was negative. CONCLUSION: A positive family history was present in 53.3%
      of our adult onset SCA patients. A specific genetic diagnosis could be given in
      61.9% of dominant pedigrees with SCA3 being the most common mutation, followed by
      SCA2 and SCA6. The yield in sporadic cases was low. The fragile X premutation was
      not found to be responsible for SCA.

PMID- 16408575
TI  - Visual defects associated with vigabatrin: a study of epileptic argentine
      patients.
AB  - OBJECTIVE: The aim of the present study was to assess visual alterations in a
      population of Argentine patients treated with the antiepileptic drug vigabatrin.
      METHODS: Twenty patients receiving vigabatrin and 15 patients receiving
      carbamazepine were examined with automated perimetry using a Humphrey 120-point
      full screening strategy. In addition, scotopic flash electroretinograms were
      performed. RESULTS: Of 20 patients treated with vigabatrin, two were unable to
      cooperate with testing. Of the remaining 18 patients, all but two showed at least
      one non-detected point inside the central 40 degrees of the visual field of each
      eye. Of the 15 carbamazepine-treated patients, three were unable to perform the
      study. None of the remaining 12 patients showed visual field defects. Both a- and
      b-wave amplitudes of the scotopic electroretinogram were significantly reduced in
      12 patients receiving vigabatrin. CONCLUSIONS: Visual field defects among
      patients on vigabatrin therapy may occur with a higher frequency than previously
      recognized. The Humphrey 120-points full field screening test and
      electroretinography are useful tools to assess the visual dysfunction associated
      with vigabatrin.

PMID- 16408577
TI  - How well does neurology residency mirror practice?
AB  - OBJECTIVE: To report the residency training experience of two neurologists,
      focusing on setting and diagnoses encountered. METHODS: Data from prospective
      patient logs kept by the authors during residencies completed a decade apart were
      compared with each other and the literature. RESULTS: The range of diagnoses was
      broadly similar between residencies, as were the proportions of common or
      uncommon disorders, and the proportion of cases without a neurological diagnosis.
      Although most patients were seen in in-patient settings, the rates at which
      common neurological conditions and functional disorders were seen was comparable
      to published experiences of community neurologists. CONCLUSIONS: The diagnostic
      profile of North American neurology residency appears to be relatively stable,
      regardless of location or date of training. In several respects, the content of
      current neurology residencies mirrors clinical practice well. Changes to
      residency training are doubtless needed, but they should be guided by a clear
      understanding of the experiences of contemporary trainees.

PMID- 16408576
TI  - The reliability of ultrasound measurements of carotid stenosis compared to MRA
      and DSA.
AB  - OBJECTIVE: Carotid ultrasound (US) is a screening test for patients with
      transient ischemic attacks (TIAs) or stroke who then undergo Digital Subtraction
      Angiogram (DSA) or Magnetic Resonance Angiography (MRA). Gold standard DSA is
      invasive with inherent risks and costs. MRA is an evolving technology. This study
      compares reliability of MRA and US modes with DSA in determining degree of
      internal carotid artery stenosis. METHODS: A five year retrospective analysis of
      140 carotid arteries from patients who had carotid US and DSA, and possibly
      Magnetic Resonance Angiography was undertaken. Recorded US parameters were peak
      systolic velocity (PSV), end diastolic velocity (EDV), and ICA/CCA peak systolic
      velocity ratio. The MRA and DSA parameters used NASCET technique for measuring
      stenosis. Statistical analysis included ROC curves and Kappa computation.
      RESULTS: US grading of carotid stenosis can be made more reliable by choosing
      appropriate parameters. The best combination of sensitivity and specificity for
      stenosis > 70% in our hospital was seen at PSV > 173 cm/s (sensitivity 0.87,
      specificity 0.8, Positive Predictive Value (PPV) 0.70, Negative Predictive Value
      (NPV) 0.93, kappa 0.64 and weighted kappa 0.71). MRA kappa was 0.78, (sensitivity
      0.75, specificity 1.0, PPV 1.0, NPV 0.85). CONCLUSIONS: US parameters should be
      validated in each centre. At best, US can only approximate the accuracy of DSA,
      probably due to inherent limitations of this modality. Magnetic Resonance
      Angiography has a perfect specificity and PPV but this technique needs to be
      standardized. Simultaneous use of MRA and US for screening increases sensitivity
      to over 0.9 without compromising specificity in > 70% stenosis.

PMID- 16408578
TI  - Diffusion tensor imaging abnormalities in focal cortical dysplasia.
AB  - PURPOSE: Focal cortical dysplasia (FCD) is one of the most common underlying
      pathologic substrates in patients with medically intractable epilepsy. While
      magnetic resonance imaging (MRI) evidence of FCD is an important predictor of
      good surgical outcome, conventional MRI is not sensitive enough to detect all
      lesions. Previous reports of diffusion tensor imaging (DTI) abnormalities in FCD
      suggest the potential of DTI in the detection of FCD. The purpose of this study
      was to study subcortical white matter underlying small lesions of FCD using DTI.
      METHODS: Five patients with medically intractable epilepsy and FCD were
      investigated. Diffusion tensor imaging images were acquired (20 contiguous 3 mm
      thick axial slices) with maps of fractional anisotropy (FA), trace apparent
      diffusion coefficient (trace/3 ADC), and principal eigenvalues (ADC parallel and
      ADC perpendicular to white matter tracts) being calculated for each slice. Region
      of interest analysis was used to compare subcortical white matter ipsilateral and
      contralateral to the lesion. RESULTS: Three subjects with FCD associated with
      underlying white matter hyperintensities on T2 weighted MRI were observed to have
      increased trace/3 ADC, reduced fractional anisotropy and increased perpendicular
      water diffusivity which was greater than the relative increase in the parallel
      diffusivity. No DTI abnormalities were identified in two patients with FCD
      without white matter hyperintensities on conventional T2-weighted MRI.
      CONCLUSIONS: While DTI abnormalities in FCD with obvious white matter involvement
      are consistent with micro-structural degradation of the underlying subcortical
      white matter, DTI changes were not identified in FCD lesions with normal
      appearing white matter.

PMID- 16408579
TI  - Processing and interpretation times of CT angiogram and CT perfusion in stroke.
AB  - OBJECTIVE: To determine the mean time for acquiring computed tomogram perfusion
      (CTP) and CT angiogram (CTA) images in acute stroke. To determine and compare
      processing and interpretation times amongst three groups of radiologists with
      varying degree of expertise: two radiology residents (Group I), two
      neuroradiology fellows (Group II) and four consultant neuroradiologists (Group
      III). METHODS: The mean time of acquisition of CTA and CTP studies was calculated
      among ten patients presenting with acute stroke. All readers had to process the
      CTA and CTP images, interpret them (for presence or absence of thrombus and
      penumbra) and save them on the GE Advantage Windows workstation. The mean time
      for processing and interpreting these studies was calculated. RESULTS: The mean
      time for acquisition of CTA and CTP studies in the ten patients was 14.6 +/- 5.9
      minutes. The time taken for CTA processing and interpretation in Groups I, II and
      III was 2.3 +/- 1.3 min, 1.6 +/- 0.4 min and 1.5 +/- 0.7 min respectively. The
      time required for CTP processing and interpretation by the same groups was 5.2 +/
      1.7 min, 4.5 +/- 1.5 min and 4.1 +/- 1.1 min respectively. There was a
      statistically significant difference of means between Groups I and III in the CTA
      and CTP processing and interpretation times (p=0.02, p=0.01 respectively) but no
      statistical difference between Groups I and II (p=0.15, p=0.22 respectively) or
      Groups II and III (p=0.31, p=0.30 respectively). CONCLUSION: The CTA and CTP
      studies can be performed, processed and interpreted quickly in acute stroke.

PMID- 16408580
TI  - Vertebroplasty in osteoporotic spine fractures: a quality of life assessment.
AB  - OBJECTIVE: Our goal was to perform a quantitative evaluation of the improvement
      in functional capacity, quality of life, mental function, reduction in drug
      intake and impact on hospital admissions after vertebroplasty in the treatment of
      osteoporotic compression fractures. The efficacy of vertebroplasty in relief of
      pain has been addressed in previous publications but the quantitative evaluation
      of improvement in quality of life has not been addressed before. METHODS: This is
      a prospective study of 42 patients with 83 symptomatic vertebral fractures
      treated by vertebroplasty with a mean follow-up of 9.1 months. The outcome was
      measured by pre and postoperatively utilizing the Visual Analogue Scale, the
      Oswestry Disability Index, the Rolland Morris Scale for Back Pain and EuroQol-5D
      questionnaire (EQ-5D). The postoperative evaluations were performed at one week,
      one month, three month, and six month intervals thereafter. RESULTS: In 34 out of
      39 active patients, marked pain relief was noted (87%). The Visual Analogue Scale
      score improved from a mean preoperative score of 8.2 to a mean postoperative
      score of 2.9 (p=0.0000003) at one week follow up and 3.9 at the last follow-up.
      The Rolland Morris Scale for Back Pain showed a drop from a mean preoperative
      rating of 13 to a mean postoperative rating of 10, showing a 25% improvement (p=
      0.0207). The Oswestry Disability Index preoperatively was 64.4 which improved to
      43.8 postoperatively, showing a 32% improvement (p= 0.0207). The EQ-5D showed a
      mean preoperative index value of 0.097 and mean postoperative index value of
      0.592 (p = 0.0000003). All p-values were determined by the Willcoxin sign-ranked
      test. CONCLUSION: Vertebroplasty is a safe and efficacious procedure with a
      resulting improvement in pain and quality of life.

PMID- 16408582
TI  - Management of chronic subdural hematoma: a national survey and literature review.
AB  - OBJECTIVE: To survey neurosurgical practices in the treatment of chronic and
      subacute subdural hematoma in the Canadian adult population. METHODS: We
      developed and administered a questionnaire to Canadian Neurosurgeons with
      questions relating to the management of chronic and subacute subdural hematoma.
      Our sampling frame included all neurosurgery members of the Canadian
      Neurosurgical Society. RESULTS: Of 158 questionnaires, 120 were returned
      (response rate = 76%). The respondents were neurosurgeons with primarily adult
      clinical practices (108/120). Surgeons preferred one and two burr-hole
      craniostomy to craniotomy or twist-drill craniostomy as the procedure of choice
      for initial treatment of subdural hematoma (35.5% vs 49.5% vs 4.7% vs 9.3%,
      respectively). Craniotomy and two burr-holes were preferred for recurrent
      subdural hematomas (43.3% and 35.1%, respectively). Surgeons preferred irrigation
      of the subdural cavity (79.6%), use of a subdural drain (80.6%), and no use of
      anti-convulsants or corticosteroids (82.1% and 86.6%, respectively). We
      identified a lack of consensus with keeping patients supine following surgery and
      post-operative antibiotic use. CONCLUSION: Our survey has identified variations
      in practice patterns among Canadian Neurosurgeons with respect to treatment of
      subacute or chronic subdural hematoma (SDH). Our findings support the need for
      further prospective studies and clinical trials to resolve areas of discrepancies
      in clinical management and hence, standardize treatment regimens.

PMID- 16408581
TI  - The impact of a stroke prevention clinic in diagnosing modifiable risk factors
      for stroke.
AB  - OBJECTIVE: To evaluate the referral patterns of patients to a stroke prevention
      clinic (SPC) and to test the adequacy of prereferral diagnosis and management of
      modifiable risk factors for stroke. METHODS: We collected prospective data on
      consecutive patients referred to the SPC at University of Alberta Hospital in
      Edmonton, Alberta, Canada. Outcome measures included: alternate diagnoses to
      stroke or transient ischemic attack (TIA), uncontrolled or undiagnosed
      hypertension, hyperlipidemia and diabetes, therapies, and investigations leading
      to carotid endarterectomy. RESULTS: Two thousand and eleven patients were
      referred to SPC. Nearly 25% of the referrals originated from the emergency room
      and the rest from general physicians. Of the referrals, 68.7% were confirmed as
      TIA or stroke at the SPC. Among 1381 patients with TIA or stroke, 736 had history
      of hypertension. Uncontrolled hypertension was found in 265 patients (36.0% of
      those with hypertension: 95% CI: 32.5-39.5) while undiagnosed hypertension was
      found in 103 (15.9% of those without hypertension: 95%CI: 13.14-18.79). History
      of hyperlipidemia was present in 451 patients (32.6%) and 356 (78.9%: 95% CI:
      75.2-82.69) of these patients were not at target for secondary prevention. Among
      930 patients without history of hyperlipidemia, 739 (79.5%: 95% CI: 76.8-82.1)
      were diagnosed with hyperlipidemia through the SPC. Fasting blood glucose levels
      above 7.1 mmol/L in patients with and without history of diabetes were 221
      (79.2%: 95% CI: 74.5-83.9) and 66 (6%: 95%CI: 4.6-7.4) respectively. CONCLUSIONS:
      Management of risk factors for stroke needs improvement. SPCs should consider
      actively managing the classical modifiable risk factors of stroke.

PMID- 16408583
TI  - Intra-arterial thrombolysis for retinal artery occlusion: the Calgary experience.
AB  - INTRODUCTION: Retinal artery occlusion represents a medical emergency with poor
      prognosis for visual recovery. Spontaneous improvement is estimated to occur in
      less than 15% of central retinal artery occlusion (CRAO) cases and conventional
      treatments have provided only limited benefit. Intra-arterial thrombolysis has
      been reported as a potentially efficacious and safe treatment. METHODS: We
      performed a retrospective chart review of all retinal artery occlusion cases
      treated with intra-arterial recombinant tissue-type plasminogen activator (rtPA)
      from January 1998 to May 2004. Patients received Goldmann perimetry visual field
      testing at a variable interval following the procedure (2 days-2.5 years). Visual
      acuity (VA) was re-assessed in May 2004. RESULTS: Eight cases (59-77 years) were
      treated for CRAO, 6-18 hours post-onset with intra-arterial rtPA (10-20 mg over
      15-60 minutes); one case of branch occlusion (BRAO) was treated with 30 mg rtPA
      over 75 minutes, 12 hours post-onset. Among the six patients with CRAO assessed
      in clinic, three experienced improvement in VA by two or more gradations (Snellen
      lines); three improved by one gradation. However, none achieved a final VA better
      than 20/300. The case of branch occlusion improved to a VA of 20/20. All patients
      had residual monocular field defects. CONCLUSIONS: Our findings reveal a limited
      benefit for intra-arterial tPA compared to the rate of spontaneous improvement
      and conventional forms of therapy for retinal artery occlusion.

PMID- 16408584
TI  - A rehabilitation program for patients recovering from severe stroke.
AB  - OBJECTIVE: The purpose of this study was to describe the outcomes of patients
      with a severe stroke admitted to a specialized "slow stream" rehabilitation
      program and to develop a model to predict discharge destination. METHODS: Chart
      review of 196 consecutive non-ambulatory ("lower-band") stroke patients admitted
      between 1996-2001, to a specialized in-patient rehabilitation unit designed to
      accommodate the needs of patients with profound disabilities, and who were
      considered inappropriate for conventional inpatient rehabilitation programs.
      Special features of this program included the availability of an independent
      living unit, therapies tailored to individual tolerance and the opportunity to
      remain on the unit for an extended period until such time that the patients'
      rehabilitation potential had been maximized. RESULTS: Patients were admitted to
      the unit after a median of 49 days following stroke onset. Their median admission
      and discharge functional independence measure (FIM) scores were 46 and 70,
      respectively. The improvement in ability to perform self-care tasks was
      statistically significant (Z= -11.18, p<0.0001). By discharge, 54 patients (28%)
      were able to ambulate independently (with or without an assistive device), while
      142 patients (72%) remained wheelchair dependent. Eighty-five patients (43%)
      returned to their own home upon rehabilitation discharge, while the remainder
      were admitted to nursing homes or hospitals closer to the patients' home.
      Admission FIM score, age, no previous history of stroke and male sex were the
      variables found to most strongly predict discharge home. CONCLUSIONS: Patients
      with severe strokes who received individualized care on a highly specialized
      stroke rehabilitation unit achieved impressive functional outcomes despite a lag
      of seven weeks post stroke before rehabilitation was initiated. Many patients
      were no longer wheelchair dependent and almost half returned home. Active
      rehabilitation should not be limited to "middle-band" stroke patients.

PMID- 16408585
TI  - A reappraisal of rhythmic coma patterns in children.
AB  - OBJECTIVE: This study was designed to determine the prevalence of rhythmic coma
      patterns in comatose children and to ascertain the prognostic significance of
      reactive rhythmic coma patterns. METHODS: We retrospectively analyzed and
      classified electroencephalogram (EEGs) in comatose children between two months
      and 18 years of age during the period 1996 - 2003 according to modified Young's
      classification. Outcome at one-year was scored according to the Paediatric
      Cerebral and Overall Performance Category Scale. Outcomes were compared using
      Fisher's exact test and Mann-Whitney test. RESULTS: Analysis of 63
      electroencephalogram (EEG) records in 38 patients showed rhythmic patterns in 19
      records (30.2%; 9 alpha, 4 spindle, 4 theta and 2 beta coma patterns, total
      number of children = 14). Aetiology and outcome of alpha coma patterns and other
      rhythmic coma patterns were similar. In five children, one type of rhythmic
      pattern changed to another. Records with reactive rhythmic coma 66.7% (6/9), were
      associated with favourable outcome. Sixty percent of the records (6/10 records in
      seven children) with non-reactive pattern were associated with unfavourable
      outcome. This clinically significant difference did not reach statistical
      significance (lower Paediatric Cerebral and Overall Performance Category Scale
      score p= 0.14; favourable outcome p=0. 19). CONCLUSION: Rhythmic coma patterns in
      comatose children are not uncommon. Aetiology, reactivity and outcome of
      individual patterns are similar and thus make the rhythmic coma patterns distinct
      EEG signatures in comatose children. There was a clinically significant better
      outcome with reactive rhythmic coma patterns.

PMID- 16408586
TI  - Use of complementary and alternative medical therapies in a pediatric neurology
      clinic.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is increasingly used in
      adults and children. Studies on CAM in neurological disorders have focused on the
      adult population and its use among pediatric neurology patients has not been well
      characterized. OBJECTIVES: The purpose of this study was: 1) To characterize the
      prevalence of CAM in pediatric neurology patients; 2) To determine the perceived
      effectiveness of CAM in these children; 3) To compare the cost of CAM with
      conventional therapies; and 4) To describe caregiver or patient-related variables
      associated with the use of CAM. METHODS: This was a cross-sectional survey of
      patients and families attending the Alberta Children's Hospital neurology clinic
      between February and May 2004. Patients were considered eligible if they were
      between two and 18 years of age and had a known history of neurological
      disorders. Caregivers completed several self-administered questionnaires
      regarding their socio-demographic profile, their child's neurological illness,
      and their experience with CAM. Caregivers also rated their child's quality of
      life using the Pediatric Quality of Life Inventory. RESULTS: One hundred and five
      of 228 (46%) families completed the survey. The mean age of the neurology
      patients was 9.8 +/- 4.5 years. Forty-six (44%) out of 105 patients received one
      or more types of CAM, with the most common types being chiropractic manipulations
      (15%), dietary therapy (12%), herbal remedies (8%), homeopathy (8%), and
      prayer/faith healing (8%). Caregivers' sociodemographic variables or pediatric
      health-related quality of life were not significantly associated with the use of
      CAM. Fifty-nine percent of CAM users reported benefits, and only one patient
      experienced side effects. There was no significant difference in the total median
      cost of CAM compared to conventional therapies (31.70 dollars vs. 50.00 dollars
      per month). Caregivers' personal experience or success stories from friends and
      media were common reasons for trying CAM. CONCLUSIONS: The use of CAM was common
      among pediatric neurology patients. Over half of the families reported benefits
      with CAM, and side effects were perceived to be few. Physicians should initiate
      discussion on CAM during clinic visits so that the families and patients can make
      informed decisions about using CAM. Further studies should address the specific
      role of CAM in children with neurological disorders, and to determine the
      potential interactions between CAM and conventional therapies in these patients.

PMID- 16408587
TI  - Cannabinoids and dopamine receptors' action on calcium current in rat neurons.
AB  - OBJECTIVE: To study the effects of cannabinoid, glutamate, and dopamine agonists
      and antagonists on the calcium current rat sympathetic neurons. METHODS: Calcium
      current was recorded using the whole-cell variant of the patch-clamp technique.
      After expression in neuronal membranes of the cannabinoid CB1, glutamate mGluR2,
      or dopamine D1 receptor (by microinjection of the levant receptor's cDNA into the
      neuron's nucleus) agonists' and antagonists' effects were observed. RESULTS:
      Applications of agonists of the expressed receptor (0.1-10 microM) decreased the
      calcium current. The calcium current was increased after application of
      cannabinoid antagonists (AM251 and AM630); these compounds thus act as inverse
      agonists in this preparation. Glutamate and dopamine antagonists had no effects
      on the calcium current by themselves. Combined application of cannabinoids and
      dopamine, but not glutamate, agonists produced a decrement in the calcium current
      that was bigger than either of the effects seen when one agonist was applied
      alone. CONCLUSIONS: These results suggest that cannabinoid with dopamine
      receptors have an interactive inhibitory effect on the calcium current in this
      preparation, indicating that within the nervous system, receptor interactions may
      be important in the regulation of ion-channel functions.

PMID- 16408588
TI  - Tension pneumocephalus--the Mount Fuji sign.

PMID- 16408589
TI  - Prognostic indicators in an aggressive pituitary Crooke's cell adenoma.
AB  - OBJECTIVE: To investigate prognostic indicators in an aggressive Crooke's cell
      adenoma of the pituitary. METHODS: The surgically removed tumor was studied by
      histology, immunohistochemistry and transmission electron microscopy. RESULTS: An
      aggressive invasive sellar tumor removed by repeated surgeries from a 43-year-old
      woman with pituitary related Cushing's disease was classified as a Crooke's cell
      adenoma of the pituitary. The application of several cell proliferation markers
      confirmed the aggressive nature of the tumor. CONCLUSIONS: The investigation of
      the present case provides additional evidence that pituitary Crooke's cell
      adenomas may possess aggressive behavior.

PMID- 16408590
TI  - Intracranial invasion of a basal cell carcinoma of the scalp.
AB  - OBJECTIVE AND IMPORTANCE: Basal cell carcinomas are common lesions that can have
      a locally invasive behavior. The authors present a case of a scalp lesion with
      skull and dura-mater invasion that was unrecognized prior to surgical
      undertaking. CLINICAL PRESENTATION: A 66-year-old female presented with an
      extensive ulcerating lesion on the frontal scalp, deemed to be a basal cell
      carcinoma. The plastic surgery team brought her to the operating room for
      resection but subsequently backed off after the discovery of bony invasion.
      Imaging revealed extensive bony and epidural extension. INTERVENTION: Resection
      of the invaded frontal scalp, bone, dura-mater and proximal part of the superior
      sagittal sinus was performed. This was followed by a reconstructive procedure
      consisting of a duraplasty, a cranioplasty, and a skin rotation flap and partial
      thickness skin grafting. CONCLUSION: Radiological evaluation of scalp basal cell
      carcinomas should be done prior to surgery to rule out any bony or intracranial
      invasion.

PMID- 16408591
TI  - Important mycotoxins and the fungi which produce them.

PMID- 16408592
TI  - Recommendations concerning the chronic problem of misidentification of
      mycotoxigenic fungi associated with foods and feeds.

PMID- 16408593
TI  - Comparison of hyphal length, ergosterol, mycelium dry weight, and colony diameter
      for quantifying growth of fungi from foods.

PMID- 16408594
TI  - Evaluation of molecular methods for the analysis of yeasts in foods and
      beverages.

PMID- 16408595
TI  - Standardization of methods for detecting heat resistant fungi.

PMID- 16408596
TI  - Ecophysiology of fumonisin producers in Fusarium Section Liseola.

PMID- 16408597
TI  - Ecophysiology of Fusarium culmorum and mycotoxin production.

PMID- 16408598
TI  - Food-borne fungi in fruit and cereals and their production of mycotoxins.

PMID- 16408599
TI  - Black Aspergillus species in Australian vineyards: from soil to ochratoxin a in
      wine.

PMID- 16408600
TI  - Ochratoxin a producing fungi from Spanish vineyards.

PMID- 16408601
TI  - Fungi producing ochratoxin in dried fruits.

PMID- 16408602
TI  - An update on ochratoxigenic fungi and ochratoxin A in coffee.

PMID- 16408603
TI  - Mycobiota, mycotoxigenic fungi, and citrinin production in black olives.

PMID- 16408604
TI  - Byssochlamys: significance of heat resistance and mycotoxin production.

PMID- 16408605
TI  - Effect of water activity and temperature on production of aflatoxin and
      cyclopiazonic acid by Aspergillus flavus in peanuts.

PMID- 16408607
TI  - Activation of ascospores by novel food preservation techniques.

PMID- 16408606
TI  - Inactivation of fruit spoilage yeasts and moulds using high pressure processing.

PMID- 16408608
TI  - Mixtures of natural and synthetic antifungal agents.

PMID- 16408609
TI  - Probabilistic modelling of Aspergillus growth.

PMID- 16408610
TI  - Antifungal activity of sourdough bread cultures.

PMID- 16408611
TI  - Prevention of ochratoxin A in cereals in Europe.

PMID- 16408612
TI  - Recommended methods for food mycology.

PMID- 16408613
TI  - A retrospective study of mushroom poisoning in Iran.
AB  - The objective of this study was to describe the pattern of mushroom poisoning in
      adults admitted to the Loghman-Hakim Hospital Poison Center from 1992 to 2002.
      All patients > or = 12 years of age were included in the study. The frequency of
      mushroom poisoning with respect to age, sex, season, reason, place of residence,
      latent phase, clinical and laboratory findings, treatment, and outcome of
      patients was investigated. Of the 72421 poisoning cases admitted to Loghman-Hakim
      Hospital Poison Center from 1992 to 2002, only 37 were poisoned by consumption of
      toxic mushrooms. As some of the patients' files were incomplete, only 25 files
      were included in the study. Of this number, 68% were male. The patients' age
      ranged between 12 and 65 years, with a mean of 31 years of age. All cases were
      accidental and mostly from Tehran (36%) and the northern provinces (rainy
      woodlands) of Iran (32%). Autumn was the most common season for poisoning with a
      frequency of 80%. The latent phase of poisonings was between 0.5 and 12 hours.
      The most frequently reported symptoms were vomiting (84%), nausea (60%),
      abdominal pain (60%) and diarrhea (40%). Jaundice was observed in 44% of cases,
      with a 50% rate of hepatic encephalopathy. A total of 66% of patients were
      discharged and the duration range of hospitalization was 1-12 days. In
      conclusion, people should be more informed of the dangers posed by wild
      mushrooms. Training of physicians and nurses in the accurate diagnosis and
      management of patients poisoned with poisonous mushrooms would improve the rate
      of survival.

PMID- 16408614
TI  - Relation between blood- and urine-amphetamine concentrations in impaired drivers
      as influenced by urinary pH and creatinine.
AB  - Amphetamine undergoes extensive renal excretion and significant amounts are
      present in urine as the unchanged parent drug. This prompted us to investigate
      whether a quantitative relationship existed between blood and urine
      concentrations of amphetamine in the body fluids of drug-impaired drivers
      apprehended in Sweden, where this stimulant is the major drug of abuse. The
      relationship between blood and urine concentrations of amphetamine was determined
      by multivariate analysis with urinary pH and creatinine as predictor variables.
      Amphetamine was determined in blood and urine by gas chromatography-mass
      spectrometry with deuterium-labelled internal standards. The concentration of
      amphetamine in urine was about 200 times greater than the concentration in blood;
      the mean and median urine/blood ratios were 214 and 160, respectively, with large
      individual variations. The Pearson correlation coefficient between urine (y) and
      blood (x) amphetamine was r = 0.53, n = 48, which was statistically highly
      significant (P < 0.001), although the residual standard deviation (SD) was large
      (+/- 181 mg/L). The correlation coefficient increased (r = 0.60) when the
      concentration of amphetamine in urine was normalized for dilution by dividing
      with the creatinine content. When urinary pH and creatinine were both included as
      predictor variables, the correlation coefficient was even higher (r = 0.69), now
      explaining 48% (r2 = 0.48) of the variation in urine-amphetamine concentration.
      However, the partial regression coefficient for creatinine (53 +/- 28.7) was not
      statistically significant (t = 1.85, P > 0.05), whereas the corresponding
      regression coefficient for pH was highly significant and had a negative sign (
      102 +/- 32.6, t= -3.12, P < 0.005). Other factors could impact on the urine-blood
      amphetamine relationship, such as route of administration, pattern of voiding and
      time elapsed after use of the drug.

PMID- 16408615
TI  - Tissue levels of cadmium and trace elements in patients with myoma and uterine
      cancer.
AB  - The aim of this study was to investigate the cadmium (Cd), copper (Cu), zinc
      (Zn), iron (Fe), magnesium (Mg) and calcium (Ca) concentrations in uterine cancer
      and uterine myoma. Tissue levels of six elements in 15 uterine cancers and 28
      uterine myomas were measured by atomic absorption spectrometry. The samples were
      collected from women aged 32-79 (uterine myomas, uterine cancer and non-lesion
      uterine tissues from the same women). The results showed that the tissue Cd
      concentration was significantly lower in myoma than in non-lesion tissue. In
      uterine cancer, however, it was statistically significant, but only slightly
      lower than controls (the non-lesion uterine tissue). In the investigated tissues,
      the correlation between Cd concentration and age was found, but no effect of
      menopausal status or smoking habits on Cd level was detected. In uterine cancer
      tissue, a significant increase in Ca concentration and an insignificant increase
      in Mg level was observed when compared to normal uterine tissue. In uterine
      myoma, a significant increase of Mg and Mg/Ca ratio, as well as a decrease in Fe
      concentration were found. Statistical analysis showed no correlation between
      smoking habits, age, menopausal status and concentration of Cu, Zn, Fe, Mg and Ca
      trace metals in myoma or cancer tissue.

PMID- 16408616
TI  - Effect of potassium dichromate on renal brush border membrane enzymes and
      phosphate transport in rats.
AB  - Chromium is widely used in industry but exposure to chromium compounds in the
      workplace can result in nephrotoxicity. Various nephrotoxicants affect the brush
      border membrane (BBM) lining the epithelial cells of the proximal tubule, but
      there have been no studies regarding the effect of potassium dichromate
      (K2Cr2O7), a hexavalent chromium compound, on renal BBM. In the present work, the
      effect of administering a single intraperitoneal dose (15 mg/kg body weight) of
      K2Cr2O7 on rat renal BBM enzymes and inorganic phosphate (Pi) transport was
      studied. The animals were administered normal saline (control) or K2Cr2O7 and
      sacrificed 1, 2, 4 and 8 days after treatment. K2Cr2O7 induced reversible damage
      to the rat kidney function as indicated by serum creatinine (Scr) and urea
      nitrogen levels. The activities of BBM marker enzymes were significantly
      decreased in isolated BBM vesicles (BBMV) and homogenates of cortex and medulla
      on 1, 2 and 4 days after administration of K2Cr2O7 with complete recovery to
      control values after 8 days. The decrease in the activities of the enzymes was
      mainly due to changes in maximum velocity (V(max)) values, while the Michaelis
      constant (Km) remained unchanged. The sodium dependent Pi transport across BBMV
      was reduced by 50% after treatment with K2Cr2O7. Thus, the administration of a
      single dose of K2Cr2O7 leads to impairment in the functions of renal BBM. These
      results suggest that the nephrotoxicity of K2Cr2O7 may be mediated, at least in
      part, by its effect on renal BBM.

PMID- 16408617
TI  - Pattern of stingray injuries reported to Texas poison centers from 1998 to 2004.
AB  - This study examined the relationship between selected factors and all human
      exposures involving stingray injuries reported to Texas poison centers. Cases
      were obtained retrospectively from calls to poison centers in Texas and included
      all reported human exposures involving stingray injuries from 1998 to 2004. The
      distribution of cases was determined for a variety of demographic and clinical
      parameters. A total of 153 cases were identified. The reported stingray injury
      penetrance increased during the 7-year period. Of the cases with a known patient
      age, 2% were <6 years, 25% were 6-19 years and 73% were >19 years. The stingray
      injuries occurred in public areas in 54% of the cases. In 61% of cases, the
      management site was reported not to be a health care facility. Of the cases with
      a known clinical outcome, none involved no effects and 53% involved minor
      effects. The highest proportion of stingray injuries occurred during the summer
      months, particularly August. In 60% of the cases, the calls originated from
      counties along the coast. This information can be used to identify those portions
      of the population most in need of education regarding the prevention and
      treatment of stingray injuries.

PMID- 16408618
TI  - Increase in thyroid follicular cell tumors in nelfinavir-treated rats observed in
      a 2-year carcinogenicity study is consistent with a rat-specific mechanism of
      thyroid neoplasia.
AB  - The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a
      2-year oral (gavage) study on Sprague-Dawley rats at dose levels of 0 (control),
      0 (vehicle control), 100, 300 and 1000 mg/kg per day. At the end of the
      treatment, increased incidences of thyroid follicular cell hyperplasia and
      neoplasms were observed at 300 (males) and 1000 mg/kg per day (both sexes). There
      were no other treatment-related effects and no tumors at other sites. Results
      from previous studies indicated a number of effects in the liver and thyroid, as
      well as metabolic profiles that suggested nelfinavir might cause thyroid
      hyperplasia/neoplasia secondary to hormone imbalance by altering thyroid hormone
      disposition. To investigate this hypothesis, the effects of nelfinavir on gene
      expression in rat hepatocytes and liver slices (in vitro), thyroxine plasma
      clearance, and thyroid gland function were evaluated. Compared to controls, gene
      expression analyses demonstrated an increased expression of glucuronyltransferase
      (UDPGT) and CYP450 3A1 in nelfinavir-treated rat hepatocytes and liver slices. In
      rats treated with nelfinavir (1000 mg/kg per day) for 4 weeks, liver weights and
      centrilobular hepatocellular hypertrophy were increased and minimal to mild
      diffuse thyroid follicular cell hypertrophy and follicular cell hyperplasia were
      evident in the thyroid gland. Thyroid-stimulating hormone (TSH) levels were
      significantly increased (three-fold), while tri-iodothyronine (T3)/tetra
      iodothyronine (T4) and reverse T3(rT3) levels were unchanged, indicating that a
      compensated state to maintain homeostasis of T3/T4 had been achieved. Plasma 125I
      thyroxine clearance was increased and the plasma thyroxine AUC0-48 was decreased
      (24%) compared to control. In conclusion, these data indicate that thyroid
      neoplasms observed in the nelfinavir-treated rats were secondary to thyroid
      hormone imbalance. Increased thyroxine clearance contributes to the effects of
      nelfinavir on thyroid gland function and is probably a result of UDPGT induction
      that leads to elevated TSH levels in the rat and eventual thyroid neoplasia.
      These results are consistent with a well-recognized rat-specific mechanism for
      thyroid neoplasms.

PMID- 16408619
TI  - Risk evaluation of occupational exposure to methylene dianiline and toluene
      diamine in polyurethane foam.
AB  - Methylene diphenylisocyanate (MDI) and toluene diisocyanate (TDI) are widely used
      in industry to produce polyurethane foam products. Small amounts of
      methylenedianiline (MDA) and toluene diamine (TDA) are released during MDI and
      TDI polymerization and may be present in newly finished polyurethane foam parts.
      MDA and TDA concentrations in foam decline exponentially within several hours of
      demolding. MDA and the 2,4-isomer of TDA are known animal carcinogens and, in
      addition, have significant non-carcinogenic health effects. Our goal was to
      determine whether worker exposure to MDA or TDA in freshly produced polyurethane
      foams was associated with unacceptable health risks. Sampling and analysis of the
      fresh foam indicated that MDA and TDA concentrations varied considerably among
      products, but concentrations in all materials evaluated declined rapidly over
      time. We found that, under a worst-case exposure scenario, cancer risks from TDA
      exposure were approximately 5 x 10(-6), whereas cancer risks from MDA exposure
      resulted in a tumorigenic margin of exposure (MOE) of 85 000. Non-cancer chronic
      hazard indices were well below 1.0. Therefore, the potential cancer and non
      cancer health risks from MDA or TDA exposure to newly manufactured foam parts
      appear to fall well within acceptable health risk criteria.

PMID- 16408620
TI  - Methanol: toxicity of the solvent in a commercial product should also be
      considered.

PMID- 16408621
TI  - [Human blood vascular endothelial dysfunction in HIV infection].
AB  - The review presents information on the impact of human immunodeficiency virus
      (HIV) on the coagulative system in blood vessels and on the potential of
      endothelial infection in the organism and in the culture of endothelial cells
      derived in vitro from blood vessels of different tissues of the organism. It also
      discusses information on the mechanisms responsible for angiogenesis and
      apoptosis of the endothelial cells cultured in vitro under the influence of HIV
      and its proteins.

PMID- 16408622
TI  - [Detection of hepatitis C virus RNA in the liver biopsy specimens from patients
      with chronic hepatitis C and hepatocellular carcinoma by means of in situ RT
      PCR].
AB  - The in situ RT-CPR technique has been first adapted in Russia to detect hepatitis
      C virus (HCV) RNA in the samples from patients with chronic hepatitis C (CHC) and
      hepatocellular carcinoma (HC). A total of 18 patients with CHC and HC were
      examined. Fourteen (78%) samples were ascertained to be positive. A positive
      reaction was found in 2 of 3 patients with HC. A label was revealed in individual
      hepatocytes without any regularity in the distribution along the tissue section.
      A reaction was negative in all samples from control groups. The label was
      observed in both the cytoplasm and the hepatocytic nuclei. There was no
      correlation between the degree of hepatic lesion, estimated after Knodelle, the
      results of the classical RT-CPR and the in situ RT-CPR techniques.

PMID- 16408624
TI  - [Alanine aminotransferase is a substitute marker of viral hepatitis].
AB  - The incidence of viral hepatitis was compared in donors (n = 184532) with the
      increased or normal activity of alanine aminotransferase (ALT) without the
      specific markers of hepatitis - HbsAg and anti-HCV. The activity of ALT was found
      to retain its diagnostic values in preventing blood-transmitted diseases only
      with the insufficient sensitivity of the specific markers of viral hepatitis in
      donors. A prospective case-control study of the specific markers of the
      infections may be recommended to assess the quality of work of diagnostic
      laboratories.

PMID- 16408623
TI  - [Local cytokine levels and morphological parameters in chronic viral hepatitis
      C].
AB  - The association of the level of local cytokines, such as interleukin (IL)-1alpha,
      IL-2, IL-4, tumor necrosis factor-alpha (TNF-alpha), and gamma-interferon (gamma
      INF) was studied in the liver biopsy specimens from patients with chronic
      hepatitis C (CHC) with clinical and morphological indices and biochemical and
      virological findings. There was a polymorphism of clinical symptoms, as well as
      extrahepatic manifestations in the group that had significantly elevated levels
      of IL-1alpha, IL-4, and TNF-alpha, as well as decreased concentrations of IL-2
      and gamma-INF. The activity of necrotic inflammatory manifestations in the liver
      in CHC is also associated with a more pronounced shift towards an increase in the
      levels of IL-1alpha, IL-4, and TNF-alpha, and a decrease in those of IL-2 and
      gamma-INF.

PMID- 16408626
TI  - [Development of HIV infection epidemics in the Volga Federal Okrug in 1988-2003].
AB  - The paper presents the results of epidemiological surveys for HIV infection in 15
      administrative areas of the Volga Federal Okrug of Russia, starting in 1988. Two
      periods of an epidemic process in the okrug are comparatively characterized.
      Different levels of HIV prevalence in the Volga regions are shown. Some
      conditions contributing to a higher prevalence of HIV infection in some areas of
      the okrug are outlined.

PMID- 16408625
TI  - [Human recombinant antibodies to variola virus].
AB  - Eight specific antibodies to live variola virus (VV), Ind-3a strain, and 7
      antibodies to VV, Butler strain, were selected from the synthetic combinatorial
      phage display library on single-chain (scFv) human antibodies. Indirect solid
      phase enzyme immunoassay showed the ability of these antibodies to bind the VV
      strains Ind-3a, Butler, Brazil-131, Kuw-5, and Congo-2. Moreover, earlier
      selected human scFv antibodies were also tested in the reaction of binding to the
      above VV strains. The experiments could reveal the antibodies that bound alastrim
      strains more effectively that did other VV strains. The nucleotide sequences
      encoding for the selected scFv antibodies were determined.

PMID- 16408627
TI  - [Ultrastructural changes in the cells of human embryo lung fibroblasts in the
      reproduction of the coronavirus HCoV/SPb/01/03].
AB  - The reproduction of the new coronavirus HCoV/SPb/01/03 in the cultured human
      embryo lung fibroblasts (HELFBs) was electron microscopically studied. The virus
      was shown to replicate in the cultured HELFBs, by using for this a cell membrane
      system and causing profound changes in its morphology. After 24 hours of cell
      infection, there were mature and defective HCoVISPb/01/03 virions were detected
      in the vacuoles near the peripheral cisterns of the Golgi apparatus. Some of the
      vacuoles contained folded membranous structures along with virions.

PMID- 16408628
TI  - [Antiviral effectiveness of the combined use of amixine and virasole in
      experimental hemorrhagic fever with renal syndrome in sucking albino mice].
AB  - The antiviral effectiveness of the combined and single use of superlow-dose
      amixine and virasole on the course of experimental hemorrhagic fever with renal
      syndrome was studied in sucking albino mice parenterally infected with their
      virus Hantaan. The co-administration of virasole and amixine was shown to protect
      52% of the infected animals from death, which is superior to the effect of their
      monotherapy. The combined use of the drugs substantially prolongs the survival of
      albino mice after their infection and the level of brain viral reproduction
      suppression ( delta = 3.21 g) in the experimental group as compared to the
      controls and to the mice given only one of the drugs.

PMID- 16408629
TI  - [Sensitivity of influenza A/H5 viruses isolated from wild birds on the territory
      of Russia to arbidol in the cultured MDCK cells].
AB  - The effect of the antiviral drug arbidol on the reproduction of avian influenza
      A/H5 viruses was studied in in vitro experiments. The strains were isolated from
      the wild birds of Eastern Siberia and they were closely related to the 1997-2000
      viruses from South-Eastern Asia. Arbidol was shown to exert a selective
      inhibiting effect on the reproduction of these viruses in the MDCH cell cultures.

PMID- 16408631
TI  - [Enzyme immunoassay system for the detection of low-avid lgG antibodies to human
      cytomegalovirus ("CMV-diagnost")].
AB  - The new Russian enzyme immunoassay system "CMV-Diagnost" based on the detection
      of low-avid IgG antibodies has been developed for the rapid diagnosis of
      cytomegalovirus infection. The system was found not only to determine the
      strained immunity in response to cytomegalovirus, but also to judge the current
      infection from the avidity index of detectable IgG antibodies with a high degree
      of validity. The antibody avidity index of less than 30% suggests an acute stage
      of primary cytomegalovirus infection. The minimum antibody threshold bodies
      (deltaOD has been established for the correct interpretation of data on low-avid
      antibodies. deltaOD of > or =0.6 optic units was for the developed test system
      "CMV-Diagnost. A correlation was found between the serum levels of low-avid
      antibodies and IgM antibodies to cytomegalovirus at the acute stage of the
      disease.

PMID- 16408630
TI  - [West Nile virus infection of agricultural animals in the Astrakhan region, as
      evidenced by the 2001-2004 serological surveys].
AB  - Sera sampled from 2,884 farming animals in the Astrakhan region in 2001 to 2004
      were investigated by the hemagglutination inhibition test (HIT) in order to
      indicate specific antibodies to West Nile virus (WNV). HIT-positive samples were
      investigated by the neutralization test (NT). WNV antibodies were detected in all
      the examined species of animals: horses (the proportion of positive tests
      throughout the observation averaged 9.8%; the agreement with NT results was
      94.1%), cattle (6,4 and 72.%), camels (5.2 and 41.7%), pigs (3.1 and 75%), and
      sheep (2.2 and 57.1). Relationships between the environmental features of WNV in
      different natural zones, the infection rate, and the conditions of keeping
      farming animals in the Astrakhan region are analyzed.

PMID- 16408632
TI  - [Development of PCR-test system for the detection of human adenovirus infection].
AB  - The paper deals with the development of the PCR-test system that allows the
      greatest possible number of human adenovirus (AdV) serotypes in the clinical
      samples to be tested by polymerase chain reaction. Primers have been selected on
      the basis of analysis of 3'-end sequences of hexon genes of 48 AdV serotypes.
      Five laboratory human AdV strains of different serotypes and some other DNA
      viruses were used to show the high sensitivity and specificity of AdV DNA
      detection. The proposed test system was not inferior to the Russian available
      analogues in sensitivity and specificity.

PMID- 16408634
TI  - [Transcription factors SRF (serum response factor) are selectively involved in
      mechanisms of long-term synapse-specific plasticity].
AB  - In our previous investigations, it was found that nociceptive sensitization is
      followed by translation- and transcription-dependent long-term facilitation of
      synaptic responses evoked by sensory stimulations in LP11 and LP11 command neuron
      of defence behavior in snail Helix lucorum. It was found that cAMP and C/EBP
      (CCAAT-enhancer-binding protein) immediate early gene transcription factors are
      involved in mechanisms of long-term facilitation of neural response evoked by
      chemical sensory stimulation of the snail "head", whereas proteinkinase C is
      involved in synaptic facilitation induction mechanisms from other sensory neural
      input tactile receptors of the snail "head". In present work, participation of
      serum response factor (SRF) immediate early gene transcription factor in
      mechanisms of synapse-specific plasticity in LP1 neuron during sensitization in
      snail Helix lucorum was studied. It was found that sensitizing stimulation during
      intracellular olygonucleotide (used as SRF specific inhibitors) injection
      resulted in selective suppression of synaptic facilitation in LP11 neuron
      responses evoked by tactile stimulation of the snail "head". At the same time,
      development of synaptic facilitation of the LP11 neuron responses evoked by
      chemical stimulation of the snail head or tactile stimulation of foot was the
      same as in the control sensitized snails. The experimental results suggest that
      the synapse-specific plasticity during learning can by supported by selective
      neurochemical "projection" of synaptic connections on neural genome.

PMID- 16408633
TI  - [Effects of blockade of ionotropic glutamate receptors on the development of
      pentylenetetrazole kindling in mice].
AB  - Effects of mono- and dicationic derivatives of adamantane and phenylcyclohexyl on
      the petyleneterazole-induced (35 mg/kg i. p.) kindling were studied in the
      experiments on mice. Monocationic derivative of phenylcyclohexyl IEM-1921,
      effectively retarded the development of kindling beginning the dose 0.0001
      microM/kg. Memantine: derivative of adamantane (derivative of adamatane) produced
      the same effect with 100-fold increased dose. Dicationic derivative
      ofphenylcyclohexyl: IEM-1925, is able to block equally the open channels of both
      NMDA and subtype of Ca-permeable AMPA receptors. Its effect on kindling differed
      markedly from selective NMDA antagonists (IEM-1921 and memantine) in more
      complicated dose-dependence. The retardation of kindling IEM-1925 was induced at
      0.001 microM/kg. On the contrary, a 10-time lower dose: 0.0001 microM/kg,
      facilitated the development of kindling. The observed difference in the activity
      of selective NMDA antagonists and the drugs combining anti-NMDA and anti-AMPA
      potency indicates that both types of ionotropic glutamate receptors are involved
      in the mechanism of petyleneterazole-induced kindling. The integral effect of
      channel blockade evoked by drugs seems to be dependent not only upon the ratio of
      the receptor types but on the kinetics of drug action, too.

PMID- 16408635
TI  - [Relations of the EEG local and spatialtemporal spectral characteristics changes
      under hypoxia in humans].
AB  - Spatial temporal and local EEG characteristics were studied in healthy subjects
      during inhalation of hypoxic oxygen-nitrogen gas mixture with 8 % content of
      oxygen. Analysis of spectra power density, coherence, phase shift, similarity of
      dominant frequencies in the EEGs of different derivations was performed
      separately for the EEG epochs with and without visually detected patterns of
      spatial synchrony of the EEG. Apart from this, a fact of dominance of the
      frequency in the EEG spectra of corresponding derivation was taken into account
      when estimating spectral parameters. Results of the study showed that, in
      general, under hypoxia, the EEG coherence in alpha- and delta-frequency range
      decreases as compared to the background level, in beta-range growth of this
      parameter is observed, in theta-range ambiguous changes occur: in the epochs with
      patterns of spatial synchrony--growth, in other epochs--lowering. Under hypoxia,
      also occurs growth of frontal and temporal EEGs' phase shift (corresponding to
      EEGs other derivations) in delta- and theta-range. In beta-range, on the
      contrary, average level of the phase shift decreases. It was revealed that taking
      into account the fact of dominance of frequency in the local EEG spectra is
      necessary for correct interpretation of the EEG spatial and temporal parameter
      analysis' results. A mathematical model of interaction between processes with
      different frequency characteristics is suggested, which explains some facts
      obtained in the study.

PMID- 16408636
TI  - [The role of D1 and D2 dopamine receptors of the rat nucleus accumbens in
      immunostimulation].
AB  - The analysis of the immune response changes in Wistar rats has shown that
      bilateral electrolytic lesions of the nucleus accumbens characterized by a high
      density of D1 an D2 dopamine (DA) receptors resulted in a decrease of the immune
      response to SRBC. Administration of selective agonists of D1 and D2 DA receptors
      to sham-operated animal: 20 mg/kg of SKF 38393 or 1.0 mg/kg of quinpirol,
      respectively, produced significant enhancement of plaque- and rosette-formation.
      However, the immune response level in the damaged rats did not increase following
      quinpirol administration, but was maintained at control values, rather. At the
      same time, activation of D1 DA receptors in rats with destructed nucleus
      accumbens did not affect the immune response level as compared to that of sham
      operated animals receiving SKF 38393. The data obtained give evidence of
      involvement of D2 DA receptors of the nucleus accumbens in immunomodulation,
      although D2 DA receptors of other brain structures may also contribute to this
      process. D1 DA receptors of this localization seem not to play any important role
      in the immune response control.

PMID- 16408637
TI  - [Changes in the electromechanical activity in the course of tetanic contraction].
AB  - The functioning of excitation-contraction coupling during tetanic contraction was
      investigated on frog skeletal muscle. The effect of the calcium release blocker
      dantrolene was tested on electrically evoked twitches and tetanic contractions.
      It was shown that the first: developmental stage of tetanus is inhibited by
      dantrolene as well as a twitch contraction, and does not influenced by calcium
      free medium. This substantiates it as based on "voltage dependent Ca-release"
      (VDCR) mechanism of activation, when depolarization directly opens the rhyanodin
      receptor calcium channels. The next stage: the long lasting plateau of tetanic
      contraction, is directly dependent on external Ca2+ entry and also inhibited by
      dantrolene, and therefore may be described as "calcium-induced Ca-release" (CICR)
      activation mechanism. It is proposed that such change in ECC mechanism taking
      place during tetanic contraction, can occur also in conditions of natural muscle
      activity, because of its rhythmical nature.

PMID- 16408638
TI  - [Comparative analysis of the cardiac glycosides action on the growth of the
      cardiac tissue explants].
AB  - The method of organotypical cell culture was used. The long-term cell culture of
      cardiac embryonic tissue of 10-12-days old chicken was investigated. The effects
      of ouabaine, strophantin K and digoxin on the growth of cardiac tissue explant
      were measured. The ouabain concentration which stimulates activity of Na+, K+
      ATPase as the signal transducer, was determined. It was equal to 10(-10) M.
      Strophantin K and digoxin stimulate growth of cardiac tissue in concentration
      equal to 10(-16) M and 10(-18) M, resp. The data obtained show that application
      of cardiac glycosides led to control of cardiac tissue growth in dose-dependent
      manner. We hypothesize that alpha3 isoform of Na+, K+-ATPase is a signal
      transducer that controls the cardiac cell metabolism and growth.

PMID- 16408639
TI  - [Estimation of age-related changes in the regulation of peripheral blood flow in
      humans].
AB  - The age-dependent features in the state of skin microvascular bed has been
      studied with laser Doppler flowmetry in healthy volunteers of different age
      groups. To reveal the reaction of skin blood flow in response to short-term
      ischemia, the occlusive test has been carried out. To estimate the contribution
      of rhythmic components to blood flow signal, continuous wavelet-transform
      spectral analysis was used. Age-dependent increase of pulse-wave amplitude and
      decrease of respiratory wave amplitude reflecting age-dependent changes in
      functioning of arteriolar and venular links of microvascular bed have been
      observed at rest. In response to short-term ischemia the age-dependent reduction
      of reserve resources has been revealed in functioning of arteriolar link of
      microvascular bed. The reduction of activity of myogenic, neurogenic and
      endothelial regulation systems have been shown at rest in ageing.

PMID- 16408640
TI  - [The effect of head-down hypokinesia on functional state of diaphragm in rats].
AB  - The effects of long-term (21 days) head-down (-30 degrees) hypokinesia (HDH) on
      respiratory system and a functional state of diaphragm were investigated in rats.
      Minute ventilation, oesophageal and abdominal pressure, integrated electrical
      activity of diaphragm were measured in control and experimental group (after 21
      days of HDH) of animals. The measurements were made in several body positions
      atresting and in occlusion breathing. The results indicate that HDH causes
      reduction in minute ventilation of lungs, decrease in orthostatic stability and
      functional reserve of the respiratory system capacity. It was established that
      the basic mechanism of HDH respiratory effects is contractile failure of
      diaphragm related to damage in excitation-contraction coupling in its muscular
      fibres.

PMID- 16408641
TI  - [Molecular mechanisms of stress].
AB  - Data on molecular mechanisms of stress are presented (appearance of stress
      proteins in the blood, as well as products of peroxidation products of lipids,
      and changes of the cell ion balance in stress). Particular accent was made on
      appearance of endogenous inhibiting agents in the blood: Na+,K+-ATPase, in
      response to extremal factor actions inducing stress.

PMID- 16408642
TI  - [The influence of the rat maternal environment on the behavior of offspring].
AB  - In Wistar's rats, the postnatal influence of maternal behaviour on the motor and
      emotional state and the anxiety level of the posterity born from the intact rat
      mothers-ambidexter but reared by the intact mothers-ambidexter with the motor
      deficit, were investigated. From the first day of life, the rat-mothers with the
      removed part of the sense-motor cortex (right or left) nursed and reared the
      litter. It was discovered that the reduction of motor activity and increase of
      negative emotional responses occurred in experimental litter at the age of 1
      month as compared with the control group (intact litter reared by the ersatz
      healthy rat-mothers). In the test of elevated cruciform maze, a high level of
      anxiety was discovered. The experimental posterity showed an emotional tension as
      the dominant state. Left-side lesion of the sense-motor cortex of the ersatz
      mother resulted in a rougher disorder in the emotional state and movement than
      after right-side lesion.

PMID- 16408643
TI  - [Study of autacoids role in the regulation of circadian rhythm of the human renal
      function].
AB  - The circadian rhythm of urine formation was studied in younger (27 +/- 8 yr) and
      aged (76 +/- 3 yr) males. In 11 younger healthy examined persons a decrease of
      diuresis during the night as compared with the day time was due to a rise of
      solute free water reabsorption. In 31 aged males the change of the urine
      formation rhythm with increase of the nocturnal diuresis is based on a rise of
      osmolal clearance combined with an increase of the solute free water
      reabsorption. It is shown that blockade of autacoid secretion leads to
      normalization of the diuresis circadian rhythm. In 10 aged men, nocturia was due
      to a decrease of vasopressin secretion which resulted in a decrease of the solute
      free water reabsorption and an increase of diuresis. The obtained data are
      considered as an evidence for the role of renal autacoids, alongside with
      vasopressin, in regulation of the circadian rhythm of the kidney function.

PMID- 16408644
TI  - [Influence of carbachol on the kinetic parameters of the contractile response to
      noradrenaline in the rat vas deferens].
AB  - Graphic and mathematical analysis of kinetics of the rat vas deferens contractile
      response to noradrenaline showed that alpha1-adrenoceptors mediating the
      contraction were in different functional states. In some organs, these receptors
      were homogeneous with the Hill coefficient n = 1 (the linear mode of the
      Scatchard plot), in the others--not homogeneous, with n > 1 (not linear mode of
      the Scatchard plot). Carbachol increased the contractile response to
      noradrenaline. As in the control, two types of response were revealed: 1. The
      Hill coefficient n < 1 (biphasic mode of the Scatchard plot) with two pools (high
      and low affinity) of alpha1-adrenoceptors, and 2. The Hill coefficient n = 1 (the
      linear mode of the Scatchard plot). These results suggest that the influence of
      carbachol is caused by the local interaction of M-cholinergic and alpha1
      adrenergic systems.

PMID- 16408645
TI  - [The effect of social isolation during juvenile period on the sexual arousal in
      adult rats].
AB  - The effects of chronic postweaning social isolation combined with subsequent
      resocialization on the sexual arousal were studied in male rats with inherited
      stress-induced arterial hypertension (ISIAH strain) and in Wistar rats. Young
      males were isolated on the Day 21 of postnatal life for 6 weeks. Then they were
      kept in groups of 5. 4-month males underwent the partition test: a receptive
      female was introduced into the male's cage, but the male and the female were
      separated by a transparent partition. The number of approaches to the partition
      and total time spent near the partition during the test served as an index of
      sexual motivation. Hormonal component of sexual arousal was estimated by
      measuring plasma testosterone level. No interstrain differences in magnitude of
      the sexual arousal were observed. However, chronic social isolation during
      juvenile period caused a genotype-dependent diminution of sexual motivation in
      the adult male rats of both strains. The decrease of sexual motivation in ISIAH
      rats was more pronounced as compared to Wistar rats. Moreover, the social
      isolation during the juvenile period completely abolished the female-induced rise
      in plasma testosterone in ISIAH and Wistar male rats. Plasma corticosterone level
      was increased during the period of sexual arousal, but this rise of
      corticosterone was not affected by the social conditions during postweaning
      period.

PMID- 16408646
TI  - [The 80th anniversary of the I. P. Pavlov Institute of Physiology of the Russian
      Academy of Sciences].

PMID- 16408647
TI  - [Chemical plasticity of cerebral neurons in the dynamics of goal-directed
      behavior].
AB  - The main purpose of the study was to establish physiological regularities and
      neurochemical mechanisms of the participation of cortical neurons of cats in
      performance of food-seeking behavioral systemoquanta. The study shows that
      individual stages of food-seeking systemoquantum are characterized by different
      sensitivity of the visual cortex to neuromediators. The author considers
      combination of methods of functional neurochemistry and the theory of behavioral
      quantization to be advantageous in a certain way, because it reveals a possible
      association between neurochemical mechanisms of involvement of individual neurons
      and the stages of the development of behavioral systemoquantum.

PMID- 16408648
TI  - [Scientific ideas of I. M. Sechenov, and neurophysiological studies of system
      stress conditions in occupational healthcare].
AB  - Occupational healthcare is one of the priority directions of modern sciences of
      life. Its achievements are based upon scientific ideas of Sechenov, the first
      Russian explorer of brain bioelectric activity. The modern neurophysiologic
      methodology of formalized quantitative evaluation of homeostasis in the higher
      brain structures allows optimization of early etiological diagnostics and
      prevention of stress reactions of central nervous and cardiovascular systems of
      workers exposed to hazardous factors of industrial environment.

PMID- 16408649
TI  - [New approaches to cholelithiasis prevention in young patients].
AB  - The purpose of the study was to evaluate efficacy of poliphepan and hepabene as
      components of complex therapy in patients with chronic cholecystitis (CC). The
      subjects were 33 CC patients with biliary tract (BT) dyskinesia and biliar
      sludge. Application of the drugs led to significant improvement of clinical
      symptoms and the parameters of BT functional condition, as well as to decrease of
      bile lithogenicity and improvement of life quality.

PMID- 16408650
TI  - [Conception of health risks and its place in the system of sociohygienic
      monitoring (problems and approaches to their solution)].
AB  - The author describes the milestones of the development of health risk analysis
      methodology within the system of sanitary and hygienic monitoring. He gives
      definitions of risk of disorder of sanitary-and-epidemiological well-being of
      population, acceptable, target, and maximum permissible risk. The author
      considers methods of practical application of risk analysis methodology for
      quantitative evaluation of health detriment in the interests of authorities of
      various levels. The united role here belongs to Interdepartmental commission on
      risk evaluation. The author analyzes prospective directions and the main problems
      of further development of scientific and juridical fundamentals of risk
      evaluation methodology that will be topical within the nearest years.

PMID- 16408651
TI  - [Evaluation of the effect of climatic warming on population health is a new task
      of preventive medicine].
AB  - Climatic warming in Russia presents a real hazard to population health. The
      authors consider effects of warming on prevalence of a range of infectious and
      parasitic diseases and stress that nowadays the most sufficient evedence has been
      obtained for West Nil fever and Crimea fever. Long-term dynamic stationary
      observations are necessary to obtain sufficient data on other infectious diseses.
      In cities abnormally high temperatures cause elevation of cardiovascular
      mortality, including myocardial infarction mortality, as well as growth of
      drowning and suicide rate.

PMID- 16408652
TI  - [Risk control strategy in the sphere of circulation of pharmaceuticals].
AB  - The article deals with classification of pharmaceutical risks and methodical
      approaches to their control in the system of governmental regulation of
      pharmaceuticals. According to the origin of risks and possibilities of their
      control, the authors distinguish "outer risks", not controlled by a consumer, and
      "inner risks", whose probability can be lowered by a consumer. Among the "outer
      risks" there are systematic risks, expressed by probability of adverse effects,
      and diversified risks, associated with pharmaceutical quality, practice of their
      administration and application, and partly--with insufficient knowledge of them.
      As an example the authors analyze risks associated with pharmaceutical quality of
      medicaments withdrawn from drug-stores by Ministry of Health of Russian
      Federation. In order to control such risks, the authors offer classification of
      pharmaceuticals according to the degree of controllability of manufacturing
      process, the ways of administration of a pharmaceutical (pharmaceutical dosage
      form), the severity of harm that can be caused to a consumer due to a defect not
      revealed by the manufacturer, and the degree of risk for population health. The
      authors reckon that the methodical approaches to pharmaceutical risk control may
      be used in evaluation of existent mechanism of providing safety for a
      pharmaceutical consumer, as well as in development of State strategy of
      increasing pharmaceutical safety.

PMID- 16408653
TI  - [The problem of goiter. Geoecological aspects].
AB  - The study determined the leading role of such geographic and geological factor as
      geological formations (mineralogical composition, structure, and the degree of
      metamorphism), tectonics, history of geological development, relief, and
      paleorelief in the microelementary status of the biosphere. The study proved that
      thyroimmunological profile of patients with goitre and geographic-and-geological
      conditions of the area are closely connected. The microelementary map of
      Bashkortostan regions was developed.

PMID- 16408654
TI  - [Adrenal gland surgery].
AB  - The authors of the article analyze more than 30-year experience of surgical
      treatment of adrenal gland diseases, offering a detailed description of clinical
      and morphological features of the main nosological forms such as Itsenko-Cushing
      disease and syndrome, primary hyperaldosteronism, pheochromocytoma,
      incidentaloma, and malignant adrenal tumors. The paper contains basic diagnostic
      criteria, indications to operative treatment, and extents of surgery for each of
      the diseases considered, as well as comparative analysis of peculiarities of
      conventional ("open"), and endoscopic adrenal gland surgeries. The article
      demonstrates significance of various immunohistochemical markers in
      differentiation between malignant and benign adrenal tumors.

PMID- 16408655
TI  - [Pathophysiology and reformation of higher medical education].

PMID- 16408656
TI  - [Oxidant stress and endothelial dysfunction].

PMID- 16408657
TI  - [Disturbances of blood rheology in chronic generalized parodontitis in
      combination with gastrodoudenal diseases].

PMID- 16408658
TI  - [Changes in content of biologically active amines in plasma and blood cells in
      bronchial asthma].
AB  - We studied concentration of histamine (Hs), serotonin (St) and catecholamines
      (CA) in the cells and plasma of venous and capillary blood of 466 patients with
      bronchial asthma (BA) and 40 controls free of BA. It was found that blood cells
      sorb, secret Hs, St and CA and participate in exchange of Hs, St and CA between
      tissues and blood. Contents of Hs, St and CA in BA patients is increased but CA
      decreased in the cells and plasma of capillary blood. Such distribution between
      Hs and CA can be explained by changed activity of histidindecarboxilase necessary
      for histamine synthesis. Capillarovenous difference by Hs, St and CA detected in
      the control group was also found in BA, being more pronounced in exogenic BA. It
      is suggested that BA patients have disturbed tissue-blood barrier and systemic
      alterations of synthesis and utilization of biogenic amines in blood of BA
      patients.

PMID- 16408659
TI  - [Platelet aggregation in modulation of the pathway L-arginine-NO in rats with
      cerebral ischemia].
AB  - Platelet aggregation in the plasma of rats with brain ischemia and modulation of
      L-arginine-NO pathway were studied in experiments (Born method using analyzer AP
      21103AO SOLAR). We used L-arginine and inhibitors of NO-synthase: nonselective
      inhibitor Nomega-nitro-L-arginine methyl ester, selective inhibitors of neuronal
      NO-synthase-7-nitro-indazole and selective inhibitor of inducible NO-synthase-S
      methylisothiourea. We found that an increase in platelet aggregation in rat
      plasma observed in both periods is mediated via NO: in an early period of brain
      ischemia it depends on neuronal NO-synthase and in a late period--on inducible NO
      synthase. Moreover, a nonselective inhibitor of all isoforms of NO-synthase
      (including endothelial NO-synthase) Nomega-nitro-L-arginine methyl ester
      possesses proaggregant properties. On the other hand, L-arginine in combination
      with 7-nitro-indazole and S-methylisothiourea induces maximal antiaggregatory
      effect. These data allows us to suppose that endothelium-derived NO decreases
      platelet aggregation in brain ischemia-reperfusion in rats.

PMID- 16408660
TI  - [The relationship of the nitric oxide level with angiotensin-converting enzyme
      activity in the chest injury].
AB  - We have studied NO production, ACE activity and their correlation in pleural
      fluid of patients with and without lung wound, in the blood serum of the wounded
      and blood donors. Chest wound was associated with a significant elevation of NO
      levels in all study groups versus controls. The greatest increase of ACE activity
      was observed in pleural fluid of patients with a lung wound. There was a negative
      correlation between NO and ACE in pleural fluid of patients with a lung wound. In
      all the other groups, a positive correlation between NO and ACE was revealed. ACE
      overactivity in the pleural fluid may be one of the factors of impaired
      relationship between NO and ACE in lung wound. Determination of ACE activity in
      the pleural fluid may serve as a diagnostic criterion of the lung injury.

PMID- 16408661
TI  - [Endotoxin aggression in pathogenesis of DIC-syndrome in children with urgent
      surgical pathology of the abdomen].
AB  - The data obtained on 19 children aged 3 months to 14 years with urgent abdominal
      inflammation (gangrenous appendicitis, perforative Meckel's diverticulum,
      intestinal obstruction complicated by peritonitis) support suggestion about
      underlying endotoxin aggression in pathogenesis of disseminated intravascular
      coagulation.

PMID- 16408662
TI  - [The role of interleukin-5 in manifestation of bronchial hyperreactivity (an
      experimental study)].
AB  - Mechanography was used to study contractile reaction of airway smooth muscles in
      experimental bronchial asthma in intact guinea-pigs and those incubated with IL
      5. Development of experimental bronchial asthma (BA) in the animals leads to
      enhancement of contractile reactions of bronchial smooth muscles in response to
      histamine action. The exposure to IL-5 of the preparations of bronchial smooth
      muscles increases histamine-mediated bronchial contractility. This may explain
      the phenomenon of IL-5-mediated bronchial hyperreactivity in the absence of
      eosinophilic damage to the tissues. Expression of mRNA of IL-5 receptor alpha
      chain suggests that development of IL-5-mediated hypersensitivity of bronchial
      smooth muscles occurs due to the presence of a relevant IL-5 receptor on their
      surface.

PMID- 16408663
TI  - [Effects of subchronic introduction of phenamine and haloperidol on development
      of spontaneous catalepsy in mice].
AB  - The development of spontaneous and haloperidol-provoked catalepsy was
      investigated in more than 200 mice. It was found that spontaneous and
      haloperidolic catalepsies have the same mechanism of development. Injections of
      amphetamine followed by injections of haloperidol led to persistent changes of
      cateleptogenic behavior in mice. Less duration of spontaneous catalepsy may
      reflect functional condition of catecholaminergic brain systems similar to that
      of patients with psychotic disorder.

PMID- 16408665
TI  - [Influence of cell therapy and alimentary correction on the condition of
      microcirculatory system in experimental dyslipidemia].
AB  - A comparative analysis of the impact of cell therapy (allogenic fetal liver
      cells, stem cells of autologic bone marrow) on lipid homeostasis,
      microcirculatory disturbances and structural changes in some organs was made
      using the atherosclerosis model in guinea-pigs. A positive effect of cell therapy
      on these parameters was established. The effect was stronger and prolonged after
      transplantation of stem cells. Atherogenic diet weakens the effect of cell
      therapy. Thus, cell therapy is more effective in restriction of atherogenic risk
      factors.

PMID- 16408664
TI  - [Modelling of intrauterine hypoxia].
AB  - An experimental model of chronic intrauterine hypoxia is proposed. This model
      reflects the most typical posthypoxic impairments for the above pathology:
      intrauterine growth retardation, alterations in the placental parameters,
      posterity death in the neonatal period, physical retardation, postnatal disorders
      in the CNS functions.

PMID- 16408666
TI  - [Leukocyte-modulating and antioxidant activity of blood serum and bronchoalveolar
      lavage fluid in the course of the decompression period of long crush syndrome].
AB  - We studied leukocyte-modulating activity (LMA) and antioxidant activity (AOA) of
      blood serum and bronchoalveolar lavage fluid (BAL) in the course of a
      postcompression period of crush syndrome (CS) in rats. CS was modelled by
      compression of the left back leg of the animal with metal vice (compression area
      5 cm2, duration 4 hours). In CS decompression, LMA of both the serum and BAL was
      high. On decompression day 1 there was a compensatory growth of serum and BAL
      AOA, its fall on day 3 and 7 and recovery by day 21. Calculation of the
      coefficient of LMA to AOA shows imbalance between pro- and antioxidant systems
      with development of oxidant stress. Thus, prevalence of blood and lung LMA over
      AOA on intermediate stages of CS may cause stimulation of destruction in hepatic
      and pulmonary tissues with development of inflammatory reaction.

PMID- 16408667
TI  - [Yttrium- Aluminium Garnet Crystal (I)].
AB  - The Yttrium- Aluminum Garnet Crystal is synthetically obtained and represents the
      active medium of the Nd: YAG, Ho: YAG, Er: YAG lasers. These solid state lasers
      showed very good results in Ophthalmology, due to their emission in different
      regimes (continuous wave or giant short pulses), at different wavelengths (near
      IR and starting from it in UV or visible spectre), the ability to focus the
      radiation through simple optic systems or the transmission to narrow, hard
      accessible spaces using flexible optic fibers. The high efficiency of these
      lasers reported in ophthalmology is obtained by the photo-disruptive or thermic
      mechanism of the laser beams. This paper introduces the properties of the laser
      radiation, the structure and the way the YAG laser works and the applications of
      these lasers in Ophthalmology (such as posterior capsulotomy, iridotomy or
      trabeculoplasty) as well.

PMID- 16408668
TI  - [Epiretinal macular membranes].

PMID- 16408669
TI  - [Superior palpebral basocellular carcinoma].
AB  - We present the case of a 48 years old female patient with a basal cell carcinoma
      located on the inferior eyelid.

PMID- 16408670
TI  - [Toxocara canis central chorioretinitis].
AB  - This issue presents the case of a patient which presents monolateral
      chorioretinitis caused by Toxocara canis.

PMID- 16408671
TI  - [Fungal endogenous endophthalmitis--case report].
AB  - This paper presents a particular case of endogenous candida endophthalmitis, at a
      patient with lots of risk factors; the correct diagnosis was relatively late; it
      had been surgically solved by posterior vitrectomy.

PMID- 16408672
TI  - [Autologous serum utilization in patients with lacrimal hyposecretion and
      persistent epithelial defects of cornea--clinical study].
AB  - Autologous serum was supposed to be efficient in the treatment of
      keratoconjunctivitis sicca and persistent epithelial defects. 14 of 24 eyes of
      patients with keratoconjunctivitis sicca improved fluorescein and rose Bengal
      scores. 3 of 6 eyes with persistent epithelial defects healed completely after
      this treatment and 2 improved fluorescein and rose bengal scores. All patients
      had been unsuccessfully treated with conventional treatment. Allergic or immune
      adverse reactions were not present and economical benefit was appreciated by some
      patients with poor socioeconomic condition.

PMID- 16408673
TI  - [Phacoemulsification with Advan-Tec system and Neosonix handpiece].
AB  - PURPOSE: The comparative analyses of the standard Legacy 20000 efficiency and the
      AdvanTec Legacy efficiency take into consideration the effective
      phacoemulsification time, power, and the postoperative clinical outcomes.
      MATERIAL AND METHODS: Retrospective clinical study which comprises 2 groups of
      patients operated on with phacoemulsification: 200 eyes were operated on using
      the classic handpiece of the Legacy 20000 system; 200 eyes were operated on using
      the AdvanTec Legacy system and the NeoSoniX handpiece. RESULTS: The effective
      phacoemulsification time in the standard Legacy group was under 0.4 min in 40
      cases (20%), between 0.4-1.2 min in 120 cases (60%), and more than 1.2 min in 40
      cases (20%). The effective phaco time in the AdvanTec-NeoSoniX group was under
      0.4 min in 118 cases (59%), between 0.4-1.2 min in 72 cases (36%) and more than
      1.2 min in 10 cases (5%). The mean phacoemulsification power varied between 19
      38% in the first group and 14-22% in the second group. Descemetic striae and
      corneal edema on the first postoperative day were observed in 38 eyes (19%) in
      the Legacy standard group, and 18 eyes (9%) in the AvanTec-NeoSonix group.
      CONCLUSIONS: The progression from the standard Legacy to the AdvanTec Legacy
      system with NeoSoniX handpiece led to the reduction in phacoemulsification power
      by two mechanisms, oscillation, which breaks the nucleus, and vacuum, which
      removes and evacuates the nuclear material.

PMID- 16408674
TI  - Comparative analysis of the efficacy and safety of latanoprost, travoprost and
      the fixed combination timolol-dorzolamide; a prospective, randomized, masked,
      cross-over design study.
AB  - PURPOSE: To analyse comparatively the efficacy and tolerance of latanoprost,
      travoprost and the fixed combination timolol-dorzolamide in the treatment of
      primary open angle glaucoma and ocular hypertension. METHOD: Prospective,
      investigator masked, randomized study that included 38 patients (38 eyes) with
      primary open angle glaucoma uncontrolled under beta blockers. Each patient
      received latanoprost, travoprost and the fixed combination timolol-dorzolamide
      (for 3 months each). The first drug and the order of the next drugs administered
      were randomized. The follow up period was 9 months. At the baseline and at the
      end of each therapeutic period (3 months) we determined the IOP (at 8, 10 a.m.
      and 4 p.m.), visual acuity, C/D ratio, blood pressure, heart rate and local
      tolerance. We have also photographed the eyelids, lashes, conjunctiva and iris.
      After each month of treatment we determined the IOP (at 8 and 10 am), visual
      acuity, blood pressure, heart rate and local tolerance. RESULTS: The mean initial
      IOP was 25.1 2.89 mmHg and after 9 months of treatment 21.67 4.59 mmHg. Each drug
      induced a statistically significant IOP decrease (the fixed combination timolol
      dorzolamide decreased IOP with 14.33%, travoprost with 18.39% and latanoprost
      with 22.1%). The IOP lowering was comparable for the prostaglandin derivatives
      and superior to the fixed combination timolol-dorzolamide. None of these drugs
      had a negative influence on the visual field, C/D ratio, visual acuity, blood
      pressure and heart rate. There was good local tolerance. The side effects were
      more frequent after travoprost (37) and latanoprost (22) than after the fixed
      combination timolol-dorzolamide (4 cases). The most important adverse events for
      the prostaglandin derivatives were conjunctival hyperemia, eyelashes pigmentation
      and growth, iris pigmentation. There was no necessary to stop the medication
      because of these effects. CONCLUSIONS: Travoprost, latanoprost and the fixed
      combination timolol-dorzolamide are efficient in the treatment of primary open
      angle glaucoma. The prostaglandin derivatives determined similar IOP decrease,
      which was superior to the fixed combination timolol-dorzolamide; the local
      tolerance was good, the fixed combination causing the fewest side effects.

PMID- 16408675
TI  - [Model of nictemeral variation of IOP and of rheological parameters of aqueous
      humor dynamic].

PMID- 16408676
TI  - [Considerations regarding Goldmann's rheologic equation].
AB  - PURPOSE: The aim of this paper is to verify if Goldmann's rheological concept is
      still valid. That is because the validity of this concept has been contested.
      (Beneyto P., Fernandez-Vila P.C., Perez T.M--An experimental approximation to the
      law of Goldmann: study of the dynamics of the aqueous humor outflow. Ann.
      Ophthalmol. Glaucoma, 1995, 27, 3, 160-166, Abstract in Glaucoma abstracts 1995,
      Vol. 6, nr. 3, 63.) MATERIAL: The authors sustained that Goldmann's equation has
      never been verified. On 42 normal eyes and 54 glaucomatous eyes (POAG) they
      determined aqueous flow by fluorophotometry, IOP by aplanotonometry and
      considered a value of 9mmHg as normal episcleral veins pressure. The results they
      obtained showed that in 47% of the cases the fluorophotometric values were with
      over 1microl/min higher then the calculated values using Goldmann's equation. So,
      they concluded that Goldmann's equation could be wrong. METHOD: There are two
      outflow pathways for the aqueous humor, trabecular and uveoscleral. Obviously,
      the uveoscleral outflow (Fu) summed with the trabecular outflow (Ftr) must be
      equal with the aqueous flow (FIN), and the total outflow facility (CTRU) must be
      the sum of the trabecular outflow facility (Ctr) and uveoscleral facility (Cu).
      Thereby Goldmann's equation can be written: FIN = Ftr + Fu = (Pio-Pv) * CTRU and
      Ftr = (Pio-Pv) * Ctr, Fu = (Pio-Pv) * Cu. With the authors' data we verified the
      previous equations. RESULTS: There is correspondence between clinical and
      mathematically deducted parameters. CONCLUSIONS: 1. Goldmann's rheological
      concept is still valid. 2. With proper modifications Goldmann's equation is still
      valid.

PMID- 16408677
TI  - [Clinical and epidemiological study about herpetic keratitis].
AB  - One of the most frequent eye diseases for old people, infectious keratitis, is an
      important cause of compromised life. Even if the infectious keratitis represents
      an important cause for hospitalisation and involves high expenses approached, the
      risk factors, which, eliminated, can contribute to the prevention of this
      disease.

PMID- 16408678
TI  - [Screening for diabetic retinopathy in the University Hospital Bucuresti].

PMID- 16408680
TI  - [Diagnosis and treatment of immune retinal vasculitis].
AB  - The paper purpose a diagnostic and treatment guide for the immune retinal
      vasculitis. These rare diseases sometimes asymptomatic for a long period, can
      cause severe ocular complications, with a significant decrease of visual acuity.
      The prognosis depends in most of cases on an early diagnosis and a correct
      treatment.

PMID- 16408679
TI  - [Retinal venous occlusion and intraocular pressure].
AB  - PURPOSE: To highlight the etiopathogenic correlations between the changes of
      intraocular pressure (IOP) and the retinal venous occlusion (RVO). METHOD: A
      prospective clinical study for a period of 2 years (01.01.2003-12.31.2004) that
      included two groups of patients: group A (31 patients) with POAG and group B (14
      patients) with OHT, homogeneous concerning the repartition on groups of age, sex,
      associated systemic conditions. We have evaluated the incidence of RVO and its
      characteristics and the evolution of IOP. The data have been statistically
      analysed using the Wilcoxon test. RESULTS: In the A group we have recorded a
      significantly higher incidence of RVO comparing to the B group (p=0.0031). In
      most of the cases, the site of OVR in both groups has been localised at the optic
      nerve head and accompanied by the fall of IOP comparing to the fellow eye.
      CONCLUSIONS: The rise of IOP represents an important risk factor for RVO, and
      particularly in the presence of other risk factors, the normalisation of IOP is
      necessary. The glaucomatous changes of optic nerve head have a major role in the
      apparition of this type of retinal vascular pathology. The changes of IOP can be
      "hidden" by the occurrence of RVO.

PMID- 16408681
TI  - [Ocular hypertension and glaucoma].
AB  - PURPOSE: To examine the relationship of ocular hypertension (O.H.) and primary
      open angle glaucoma (P.O.A.G.) with reference of two patients which presented
      papillo-campimetry changes after 38 and respectively 24 years after O.H. was
      diagnosed (at levels between 30 and 45 mm Hg). The ratio IOP/F (feeding of the
      papilla and retina) is time depending, e.g. IOP x T/ F x 1/T. Because in the
      O.H.T.S. values of Goldmann applanation tonometry was not corrected by the
      central corneal thickness; and also SWAP technique was not available by that
      time, the author considers confirmation of POAG at the term of 5 years as high as
      14,6-24,6%. Thus, the O.H. must be named as pre-campimetry glaucoma, when the IOP
      exceeds 25-26 mm Hg.

PMID- 16408682
TI  - [Histological studies in cataract--effect of USIOL IOL's in posterior capsule of
      rabbits].
AB  - Cataract represents a degenerative process of lens structures with multifactor
      causes. STUDY OBJECTIVES: are to present histopathological modificatios at
      different types of cataract and to demonstrate the USIOL lens effects at rabbit
      posterior capsule, after extracapsular surgery. MATERIAL AND METHOD: It was
      performed a comparative histological study at different types of cataract. It was
      implanted PMMA and acrylic USIOL lens at 2 rabbits. Follow-up was for 3 months
      and after ECCE it was performed histopathological examination of posterior lens
      capsules. RESULTS AND CONCLUSIONS: There are few histological observations which
      can suggests the cataract cause. USIOL implants are well tolerated and the
      posterior lens capsule modifications after IOL implantation are not important.

PMID- 16408683
TI  - The New England Air Quality Forecasting Pilot Program: development of an
      evaluation protocol and performance benchmark.
AB  - The National Oceanic and Atmospheric Administration recently sponsored the New
      England Forecasting Pilot Program to serve as a "test bed" for chemical
      forecasting by providing all of the elements of a National Air Quality
      Forecasting System, including the development and implementation of an evaluation
      protocol. This Pilot Program enlisted three regional-scale air quality models,
      serving as prototypes, to forecast ozone (O3) concentrations across the
      northeastern United States during the summer of 2002. A suite of statistical
      metrics was identified as part of the protocol that facilitated evaluation of
      both discrete forecasts (observed versus modeled concentrations) and categorical
      forecasts (observed versus modeled exceedances/nonexceedances) for both the
      maximum 1-hr (125 ppb) and 8-hr (85 ppb) forecasts produced by each of the
      models. Implementation of the evaluation protocol took place during a 25-day
      period (August 5-29), utilizing hourly O3 concentration data obtained from over
      450 monitors from the U.S. Environment Protection Agency's Air Quality System
      network.

PMID- 16408684
TI  - Trace gases and particulate matter emissions from wildfires and agricultural
      burning in Northeastern Mexico during the 2000 fire season.
AB  - An inventory of air pollutants emitted from forest and agricultural fires in
      Northeastern Mexico for the period of January to August of 2000 is presented. The
      emissions estimates were calculated using an emissions factor methodology. The
      inventory accounts for the emission of carbon monoxide (CO), methane, nonmethane
      hydrocarbons, ammonia, nitrogen oxides, and particulate matter (PM). Particulate
      matter emissions include estimates for fine PM and coarse PM. A total of 2479
      wildfires were identified in the domain for the period of interest, which
      represented approximately 810,000 acres burned and 621,130 short tons emitted
      (81% being CO). The main source of information used to locate and estimate the
      extent of the fires came from satellite imagery. A geographic information system
      was used to determine the type of vegetation burned by each fire. More than 54%
      of the total area burned during the period of study was land on the State of
      Tamaulipas. However, >58% of the estimated emissions came from the State of
      Coahuila. This was because of the mix of vegetation types burned in each state.
      With respect to the temporal distribution, 76.9% of the fires occurred during the
      months of April and May consuming almost 78% of the total area burned during the
      period of study. Analysis of wind forward trajectories of air masses passing
      through the burned areas and 850-mb wind reanalyses indicate possible
      transboundary transport of the emissions from Mexico to the United States during
      the occurrence of the major wildfires identified.

PMID- 16408685
TI  - Incinerating volatile organic compounds with ferrospinel catalyst MnFe2O4: an
      example with isopropyl alcohol.
AB  - This paper concerns the incineration of isopropyl alcohol (IPA) using the
      ferrospinel catalyst MnFe2O4. It covers the preparation of the ferrospinel
      catalyst, the screening of catalytic activity, catalytic incineration testing,
      and 72-hr decay testing of the catalyst. The experimental results of catalyst
      screening reveal that the Mn/Fe catalyst is the best of five prepared catalysts
      (chromium/iron [Cr/Fe], manganese/iron [Mn/Fe], zinc/iron [Zn/Fe], nickel/iron
      [Ni/Fe], and pure magnetite [Fe3O4]). In tests of the catalytic incineration
      system used to convert IPA, 98% conversion was obtained at a space velocity of
      24,000 hr(-1), an oxygen (O2) content of 21%, 1700 ppm of IPA, and a reaction
      temperature of 200 degrees C.

PMID- 16408686
TI  - Air quality impact of the coal-fired power plants in the northern passageway of
      the China West-East Power Transmission Project.
AB  - This paper analyzes the air quality impacts of coal-fired power plants in the
      northern passageway of the West-East Power Transmission Project in China. A three
      layer Lagrangian model called ATMOS, was used to simulate the spatial
      distribution of incremental sulfur dioxide (SO2) and coarse particulate matter
      (PM10) concentrations under different emission control scenarios. In the year
      2005, the emissions from planned power plants mainly affected the air quality of
      Shanxi, Shaanxi, the common boundary of Inner Mongolia and Shanxi, and the area
      around the boundary between Inner Mongolia and Ningxia. In these areas, the
      annually averaged incremental SO2 and PM10 concentrations exceed 2 and 2.5
      microg/m3, respectively. The maximum increases of the annually averaged SO2 and
      PM10 concentrations are 8.3 and 7.2 microg/m3, respectively, which occur around
      Hancheng city, near the boundary of the Shaanxi and Shanxi provinces. After
      integrated control measures are considered, the maximum increases of annually
      averaged SO2 and PM10 concentrations fall to 4.9 and 4 microg/m3, respectively.
      In the year 2010, the areas affected by planned power plants are mainly North
      Shaanxi, North Ningxia, and Northwest Shanxi. The maximum increases of the
      annually averaged SO2 and PM10, concentrations are, respectively, 6.3 and 5.6
      microg/m3, occurring in Northwest Shanxi, which decline to 4.4 and 4.1 microg/m3
      after the control measures are implemented. The results showed that the proposed
      power plants mainly affect the air quality of the region where the power plants
      are built, with little impact on East China where the electricity will be used.
      The influences of planned power plants on air quality will be decreased greatly
      by implementing integrated control measures.

PMID- 16408687
TI  - Technology innovations and experience curves for nitrogen oxides control
      technologies.
AB  - This paper reviews the regulatory history for nitrogen oxides (NOx) pollutant
      emissions from stationary sources, primarily in coal-fired power plants. Nitrogen
      dioxide (NO2) is one of the six criteria pollutants regulated by the 1970 Clean
      Air Act where National Ambient Air Quality Standards were established to protect
      public health and welfare. We use patent data to show that in the cases of Japan,
      Germany, and the United States, innovations in NOx control technologies did not
      occur until stringent government regulations were in place, thus "forcing"
      innovation. We also demonstrate that reductions in the capital and operation and
      maintenance (O&M) costs of new generations of high-efficiency NOx control
      technologies, selective catalytic reduction (SCR), are consistently associated
      with the increasing adoption of the control technology: the so-called learning-by
      doing phenomena. The results show that as cumulative world coal-fired SCR
      capacity doubles, capital costs decline to approximately 86% and O&M costs to 58%
      of their original values. The observed changes in SCR technology reflect the
      impact of technological advance as well as other factors, such as market
      competition and economies of scale.

PMID- 16408688
TI  - Continuous determination of fine particulate matter mass in the Salt Lake City
      Environmental Monitoring project: a comparison of real-time and conventional TEOM
      monitor results.
AB  - Fine particulate matter (PM2.5) mass was determined on a continuous basis at the
      Salt Lake City Environmental Protection Agency Environmental Monitoring for
      Public Awareness and Community Tracking monitoring site in Salt Lake City, UT,
      using three different monitoring techniques. Hourly averaged PM2.5 mass data were
      collected during two sampling periods (summer 2000 and winter 2002) using a real
      time total ambient mass sampler (RAMS), sample equilibration system (SES)-tapered
      element oscillating microbalance (TEOM), and conventional TEOM monitor. This
      paper compares the results obtained from the various monitoring systems, which
      differ in their treatment of semivolatile material (SVM; particle-bound water,
      semivolatile ammonium nitrate, and semivolatile organic compounds). PM2.5 mass
      results obtained by the RAMS were consistently higher than those obtained by the
      SES-TEOM and conventional TEOM monitors because of the RAMS ability to measure
      semivolatile ammonium nitrate and semivolatile organic material but not particle
      bound water. The SES-TEOM monitoring system was able to account for an average of
      28% of the SVM, whereas the conventional TEOM monitor loses essentially all of
      the SVM from the single filter during sampling. Occasional mass readings by the
      various TEOM monitors that are higher than RAMS results may reflect particle
      bound water, which, under some conditions, is measured by the TEOM but not the
      RAMS.

PMID- 16408689
TI  - Systematic development of an artificial neural network model for real-time
      prediction of ground-level ozone in Edmonton, Alberta, Canada.
AB  - Ground-level ozone is a secondary pollutant that has recently gained notoriety
      for its detrimental effects on human and vegetation health. In this paper, a
      systematic approach is applied to develop artificial neural network (ANN) models
      for ground-level ozone (O3) prediction in Edmonton, Alberta, Canada, using
      ambient monitoring data for input. The intent of these models is to provide
      regulatory agencies with a tool for addressing data gaps in ambient monitoring
      information and predicting O3 events. The models are used to determine the
      meteorological conditions and precursors that most affect O3 concentrations. O3
      time-series effects and the efficacy of the systematic approach are also
      assessed. The developed models showed good predictive success, with coefficient
      of multiple determination values ranging from 0.75 to 0.94 for forecasts up to 2
      hr in advance. The inputs most important for O3 prediction were temperature and
      concentrations of nitric oxide, total hydrocarbons, sulfur dioxide, and nitrogen
      dioxide.

PMID- 16408690
TI  - Predicting cutoff aerodynamic diameter and sharpness of single round-nozzle
      impactors with a finite impaction plate diameter.
AB  - This investigation numerically examined the cutoff aerodynamic diameter (da50)
      and the sharpness (GSD) of the particle collection efficiency curve of impactors
      with a finite impaction plate diameter. Results revealed that the inertial
      impactors have a limited cutoff aerodynamic diameter at different air velocities.
      The extreme value of the cutoff aerodynamic diameter increases with the nozzle
      diameter (W)/the plate diameter (Dc). The computed da50/Dc values of the
      impactors increase with W/Dc at various Reynolds numbers (Re) and with the nozzle
      toplate distance (S)/Dc when Re is 100. The value of GSD slightly increases with
      W/Dc for Re of 10 and 100, although the effect of S/Dc on GSD is not evident at
      various Res. The particle collection efficiency curve of the impactor with a
      lower Re is less sharp than that with a high Re at various W/Dc and S/Dc values.
      Statistical equations closely fitted the obtained numerical results for Res of 10
      3000. The equations are useful for directly calculating the cutoff aerodynamic
      diameter and the sharpness of the particle collection efficiency curve for single
      round-nozzle impactors with a finite impaction Dc.

PMID- 16408691
TI  - A predictive mechanism for mercury oxidation on selective catalytic reduction
      catalysts under coal-derived flue gas.
AB  - This paper introduces a predictive mechanism for elemental mercury (Hg(o))
      oxidation on selective catalytic reduction (SCR) catalysts in coal-fired utility
      gas cleaning systems, given the ammonia (NH3)/nitric oxide (NO) ratio and
      concentrations of Hg(o) and HCl at the monolith inlet, the monolith pitch and
      channel shape, and the SCR temperature and space velocity. A simple premise
      connects the established mechanism for catalytic NO reduction to the Hg(o)
      oxidation behavior on SCRs: that hydrochloric acid (HCl) competes for surface
      sites with NH3 and that Hg(o) contacts these chlorinated sites either from the
      gas phase or as a weakly adsorbed species. This mechanism explicitly accounts for
      the inhibition of Hg(o) oxidation by NH3, so that the monolith sustains two
      chemically distinct regions. In the inlet region, strong NH3 adsorption minimizes
      the coverage of chlorinated surface sites, so NO reduction inhibits Hg(o)
      oxidation. But once NH3 has been consumed, the Hg(o) oxidation rate rapidly
      accelerates, even while the HCl concentration in the gas phase is uniform.
      Factors that shorten the length of the NO reduction region, such as smaller
      channel pitches and converting from square to circular channels, and factors that
      enhance surface chlorination, such as higher inlet HCl concentrations and lower
      NH3/NO ratios, promote Hg(o) oxidation. This mechanism accurately interprets the
      reported tendencies for greater extents of Hg(o) oxidation on honeycomb monoliths
      with smaller channel pitches and hotter temperatures and the tendency for lower
      extents of Hg(o) oxidation for hotter temperatures on plate monoliths. The
      mechanism also depicts the inhibition of Hg(o) oxidation by NH3 for NH3/NO ratios
      from zero to 0.9. Perhaps most important for practical applications, the
      mechanism reproduces the reported extents of Hg(o) oxidation on a single catalyst
      for four coals that generated HCl concentrations from 8 to 241 ppm, which covers
      the entire range encountered in the U.S. utility industry. Similar performance is
      also demonstrated for full-scale SCRs with diverse coal types and operating
      conditions.

PMID- 16408692
TI  - Review of light-duty diesel and heavy-duty diesel gasoline inspection programs.
AB  - Emissions from diesel vehicles and gas-powered heavy-duty vehicles are becoming a
      new focus of many inspection and maintenance (I/M) programs. Diesel particulate
      matter (PM) is increasingly becoming more recognized as an important health
      concern, while at the same time, the public awareness of diesel PM emissions
      because of their visibility have combined to increase the focus on diesel
      emissions in the United States. This has resulted in an increased interest by
      some states in including heavy-duty vehicle testing in their I/M program. This
      paper provides an overview of existing I/M programs focused on testing light-duty
      diesel vehicles, heavy-duty diesel vehicles, and heavy-duty gasoline vehicles
      (HDGVs). Information on 39 I/M programs in 27 different states in the United
      States plus 9 international inspection programs is included. Information on the
      status of diesel emissions technology and current test procedures is also
      presented. The goal is to provide useful information for air quality managers as
      they work to decide whether such I/M programs would be worth pursuing in their
      respective areas and in evaluating the emissions measurement technology to be
      used in the program. Testing of HDGVs is generally limited to idle testing,
      because dynamometer testing of these vehicles is not practical, and most were not
      certified on a chassis basis. Testing of diesel vehicles has mostly been limited
      to SAE J1667 "snap-idle" opacity testing. Cost-effective technology for measuring
      diesel emissions currently does not exist, and, therefore, opacity-type
      measurements, although not effective at reducing the pollutants of most
      significant health concern, will continue to be used.

PMID- 16408693
TI  - Do negative feedback oscillations drive variations in the length of the tumor
      cell division cycle?
AB  - The cell cycle length of individual cells within a tumor cell population is known
      to vary, mainly as a consequence of differences in the length of G1 phase. A
      number of observations suggest that the distribution of G1 phase transit times is
      well described by models where the transition from G1 to S phase is governed by a
      probability mechanism. However, entry into S phase as a consequence of
      progressive accumulation of cyclin E with time, to the point where cyclin
      dependent kinase-2 (cdk2) is activated, does not provide a basis for a
      probability mechanism. We suggest that oscillation of the activity of the E2F-1
      transcription factor during G1 phase could provide a mechanism that explains the
      kinetic behavior of G1 phase cells. A negative feedback loop controlling
      oscillation is possible because activation of cdk2, following activation by
      cyclin E, phosphorylates the E2F-1 transcription factor, marking it for
      ubiquitination by the Skp2-cullin-F-box complex and subsequent proteolytic
      removal. The activity of several cellular transcription factors, including p53
      and NF-kappaB, has been shown to oscillate by negative feedback loops leading to
      ubiquitination and subsequent proteolytic degradation. The oscillatory mechanisms
      for p53 and NF-kappaB suggest that transitions from the cell cycle to apoptosis
      are also governed by probability functions.

PMID- 16408694
TI  - Transient absorption spectra and kinetics of folic acid (vitamin B11) and some
      kinetic data of folinic acid and methotrexate.
AB  - Folic acid (FA; vitamin B11) exhibits antitumor properties. Its transients,
      resulting from reaction with OH radicals, are of special interest and were
      studied by pulse radiolysis. The complex composition of FA offers the formation
      of numerous transients having different electronic structure stability
      (lifetime). Investigating their kinetic profiles of decay at various wavelengths,
      it was established that transients with very unstable electron structure (very
      short-lived radicals) tend to convert into more stable electronic structures
      (longer lived) by intramolecular electron transfer process. The biological
      importance of a FA radical depends on its concentration and on its specific
      reaction rate constant (k value) for a given process. The rate constant for the
      OH attack is k(OH + FA) = 1.1 x 10(10) L mol(-1) s(-1). Superimposed absorption
      spectra of FA radicals as well as formation and decay rate constants of total
      processes are presented. The primary spectrum is characterized by lambda = 425
      nm, epsilon = 1.64 x 10(4) L mol(-1) s(-1). The chemical structure of FA is
      similar to that of folinic acid (FNA) and of methotrexate (MTX), but their
      biological properties are different. Therefore, their rate constants for the
      reactions with e-aq and OH were also determined for comparison: k(FNA + e-aq) =
      3.1 x 10(10) L mol(-1) s(-1), k(FNA + OH) = 0.8 x 10(10) L mol(-1) s(-1), k(MTX +
      e-aq) = 1 x 10(10) L mol(-1) s(-1); k(MTX + OH) = 2.3 x 10(10) L mol(-1) s(-1),
      and k(FA + e-aq) = 1.9 x 10(10) L mol(-1) s(-1).

PMID- 16408696
TI  - The antineoplastic efficacy of the prodrug Cloretazine is produced by the
      synergistic interaction of carbamoylating and alkylating products of its
      activation.
AB  - Cloretazine {1,2-bis(methylsulfonyl)-1-[(2-chloroethyl)-2
      (methylamino)carbonyl]hydrazine; VNP40101M; 101M} is a sulfonylhydrazine prodrug
      that possesses broad spectrum antitumor efficacy against transplanted murine and
      human tumor models and has shown activity in clinical trials against relapsed or
      refractory acute myeloid leukemia. Base catalyzed activation of this prodrug
      generates two different reactive intermediates: chloroethylating species that
      covalently interact with DNA at the O6-position of guanine residues that progress
      to a G-C interstrand cross-link, and a carbamoylating agent, methyl isocyanate.
      Previous findings from this laboratory have provided initial evidence that methyl
      isocyanate can contribute to the efficacy of Cloretazine by enhancing the
      cytotoxicity of the generated chloroethylating species. This action may be due in
      part to inhibition of the DNA repair protein O6-alkylguanine-DNA alkyltransferase
      (AGT); however, activity in cells devoid of AGT indicates that other actions are
      involved in the synergistic cytotoxicity. Herein we demonstrate that O6
      benzylguanine can also produce synergistic cell kill with the alkylating
      component of Cloretazine but differs from methyl isocyanate in that the
      enhancement occurs in AGT-containing cells, but not in cells devoid of AGT.
      Methyl isocyanate generated by the decomposition of 1,2-bis(methylsulfonyl)-1
      [methylaminocarbonyl]hydrazine also acts to enhance the activity of a variety of
      DNA cross-linking agents, while only producing additive cytotoxicity with
      methylating agents. Flow cytometric studies using annexin as a marker for
      apoptosis indicate that in Chinese hamster ovary cells and in human leukemia
      cells Cloretazine-induced apoptosis is primarily caused by the generated methyl
      isocyanate. Comet assays designed to detect DNA cross-links in intact cells
      indicate that the chloroethylating species generated by the activation of
      Cloretazine produce DNA cross-links, with the co-generated methyl isocyanate
      increasing the degree of cross-linking produced by the reactive chloroethylating
      species. These findings provide further evidence that the methyl isocyanate
      produced by the activation of Cloretazine can be a major contributor to the
      cytotoxicity produced by this antineoplastic agent.

PMID- 16408695
TI  - Effect of glibenclamide on N-nitroso-N-methylurea-induced mammary tumors in
      diabetic and nondiabetic rats.
AB  - The objective of this study was to evaluate the antitumor effect of glibenclamide
      (Gli) alone or in combination with tamoxifen (Tam) on experimental mammary tumors
      induced by N-nitroso-N-methylurea (NMU) in nondiabetic and diabetic rats. For
      experimental diabetes induction, Sprague-Dawley rats were injected with
      streptozotocin (STZ) on the second day of life. For experimental mammary tumor
      induction, nondiabetic and diabetic rats were injected IP with NMU at 50, 80, and
      110 days of life. Nondiabetic and diabetic rats bearing mammary tumors were
      treated with 0.06 mg/day of Gli orally, Tam 1 mg/kg/day SC, or with the combined
      treatment (Gli + Tam). After 20 days of treatment, different responses were
      observed. In nondiabetic rats, 64% of tumors were responsive to Gli treatment
      (they regressed or remained stable), whereas 57% of tumors under treatment with
      Tam exhibited a response. Results of the combined Gli + Tam treatment indicated
      that all tumors were responsive: 58% regressed and 42% remained stable. Diabetic
      rats receiving Gli treatment did not show response to this treatment, while 65%
      of the tumors of Tam-treated diabetic rats showed regression. Histopathologic
      observation indicated an important intratumor secretion in all tumors of Gli-,
      Tam-, or Gli + Tam-treated rats. No secondary toxic effect was observed after
      treatment at any assayed doses. In conclusion, the present data demonstrate the
      in vivo antitumor action of Gli treatment on the experimental mammary tumors
      employed, indicating that Gli exerted a direct effect on tumor cells in
      nondiabetic rats. The combined Gli + Tam treatment potentiated the antitumor
      effect of each drug alone. Future research will examine the molecular aspects of
      these findings.

PMID- 16408698
TI  - [Children born with extremely low-birth-weight. American long term follow up
      shows severe functional limitation].

PMID- 16408697
TI  - Inhibition of protein kinase CKII activity by euchrestaflavanone B purified from
      Cudrania tricuspidata.
AB  - The CKII (EC 2.7.1.37) inhibitory compound was purified from the root barks of
      Cudrania tricuspidata and identified as (2S)-2-[2,4-dihydroxy-5-(3-methyl-but-2
      enyl)-phenyl]-5,7-dihyroxy-6-(3-methyl-but-2-enyl)chroman-4-one
      (euchrestaflavanone B). Euchrestaflavanone B was shown to inhibit the
      phosphotransferase activity of CKII with IC50 of about 78 microM. Steady-state
      studies revealed that euchrestaflavanone B acted as a competitive inhibitor with
      respect to the substrate ATP. A value of 16.4 microM was obtained for the
      apparent Ki. Concentration of 0.8 microM euchrestaflavanone B caused 50% growth
      inhibition of human cancer cells U937 and HeLa. Euchrestaflavanone B-induced cell
      death was characterized with the cleavage of poly(ADP-ribose) polymerase and
      procaspase-3, indicating that the inhibitor triggered apoptosis. Because protein
      kinase CKII is involved in cell proliferation and oncogenesis, these results
      suggest that euchrestaflavanone B may function by inhibiting oncogenic disease,
      at least in part, through the inhibition of CKII activity.

PMID- 16408700
TI  - [Inadequate data on drugs in cardiac arrest. Extensive, randomized trials are
      necessary--vasopressin a possible alternative].

PMID- 16408699
TI  - [Swedish extremely premature children do better seen from an international point
      of view].

PMID- 16408701
TI  - [From a controversial minor finding to the Nobel Prize. The discovery of
      Helicobacter pylori--an unlikely tale of success].

PMID- 16408702
TI  - [TNF blockade in rheumatoid arthritis can cause severe fibrosing alveolitis. Six
      case reports].
AB  - TNF-blockade has been increasingly used in the treatment of rheumatoid arthritis
      (RA). However, the safety is unclear and an increased risk of both tuberculosis
      and other infections has been identified. Recently severe fibrosing alveolitis
      has also been reported in RA-patients treated with TNF-blockade. We report a
      further six RA patients, who during treatment with infliximab or etanercept
      developed fulminant lung fibrosis with alveolitis. For four of the patients, the
      fibrosing alveolitis was fatal. All patients were RF positive and above 60 years
      and five had mild fibrosis associated with RA before TNF-blockade treatment.
      Duration of TNF-blockade treatment was for three patients only two months and for
      the other three, 20-51 months. Age above 60 years and previous lung fibrosis
      appear to be risk factors for developing fibrosing alveolitis in RA patients
      treated with TNF-blockade.

PMID- 16408704
TI  - [Antiviral agents in influenza--current recommendations. Anti-influenza agents
      are not a substitution for but a complement to vaccination].
AB  - This article summarizes a Swedish consensus guidance document on the use of
      antiviral drugs in the management of influenza. Vaccination remains the
      cornerstone for influenza prophylaxis. Treatment with neuraminidase inhibitors is
      recommended for high-risk groups and individuals hospitalised with influenza.
      Chemoprophylaxis is targeted at high-risk groups and should be considered on a
      case by case basis depending on the circumstances. Unvaccinated at-risk patients
      or seasonal vaccine strain mismatch were identified as potential indications for
      antiviral prophylaxis. Oseltamivir prophylaxis can otherwise be considered for
      influenza in a household including an at-risk individual and in outbreaks in
      hospitals and nursing homes. The use of antivirals in a pandemic situation is
      also discussed.

PMID- 16408705
TI  - [Influenza, birds and the threating pandemic. Entire society should plan for an
      extreme situation, high sick leave included].

PMID- 16408703
TI  - [Increased risk of infection with biological immunomodifying antirheumatic
      agents. Clear guidelines are necessary as shown by case reports].
AB  - Several potent immunosuppressive drugs have become available in the new
      millennium for patients with rheumatologic diseases, Crohn's disease and other
      autoimmune disorders. Five patient cases from Vaxjo central hospital (uptake area
      178 000 individuals) with Listeria meningitis, Pneumocystis jiroveci and
      tuberculosis pneumonia, Listeria sepsis, Legionella pneumonia and E coli sepsis
      are described. A doubled risk for infections has previously been observed for RA
      patients, as compared to healthy individuals. There is clearly an increased risk
      of tuberculosis (depending on the actual and historic environmental prevalence)
      for patients on TNF antagonists, and therefore tuberculosis screening is now
      mandatory before start of therapy. Since TNF has a central role in the immune
      defence, an increased risk of opportunistic infections like listeriosis.
      mycobacteriosis, and invasive fungal infections has been established. Eight
      hospitals in southern Sweden participate in a register for the use of TNF
      blockers in rheumatologic diseases (South Swedish Arthritis Treatment Group,
      SSATG). Guidelines for screening and treatment of latent and active tuberculosis,
      possible prophylactic antibiotic treatment for endocarditis and vaccination
      programs for patients on TNF antagonists are discussed.

PMID- 16408706
TI  - [Lakartidningen and natural remedies--where is the nuanced information?].

PMID- 16408707
TI  - [SBU comments a medical comment: better care of anxiety requires a joint measure-
      guided by the evidence].

PMID- 16408708
TI  - [Common cold guidelines in pharmacies not ungrounded].

PMID- 16408709
TI  - [A description of the environmental poison, mercury, raises questions].

PMID- 16408711
TI  - Doctor seer.

PMID- 16408710
TI  - [Abolish the concept "neuropsychiatry" within child and adolescent psychiatry].

PMID- 16408712
TI  - Ellis Island: palace of hope, island of fears.

PMID- 16408713
TI  - Ethical issues in forensic medicine in Rhode Island.

PMID- 16408714
TI  - Arrested, addicted: heroin users in the Rhode Island Corrections System.

PMID- 16408715
TI  - The overlapping epidemics of viral hepatitis/HIV, addiction and incarceration:
      the situation in Rhode Island.

PMID- 16408716
TI  - Correctional health care in Rhode Island: challenges and opportunities.

PMID- 16408717
TI  - The Donation Inmate Organ Network (DION): giving inmates time off for organ
      donation.

PMID- 16408718
TI  - Prisoners and organ donation.

PMID- 16408719
TI  - Case presentations of the Brown University Department of Medicine: Miriam
      Hospital Morbidity and Mortality Conference: case of internal carotid artery
      dissection.

PMID- 16408720
TI  - Route of vitamin K administration for elevated INRs in the acute inpatient
      setting.

PMID- 16408722
TI  - [Twenty years of nasal endoscopic surgery in China: where we were, where we are
      and where we're going].

PMID- 16408721
TI  - Preliminary results from the Rhode Island Violent Death Reporting System
      (RIVDRS).

PMID- 16408723
TI  - [Endoscopic endonasal surgery: technical classification, admittance and training
      system].

PMID- 16408724
TI  - [Chronic rhinosinusitis: definition, classification and treatment].

PMID- 16408725
TI  - [Indication and complication of endoscopic endonasal surgery].

PMID- 16408726
TI  - [Endoscopic endonasal skull base surgery].

PMID- 16408728
TI  - [SiRNA expression cassettes targeting VEGF effectively inhibit the growth of
      laryngeal squamous cell carcinoma cell lines].
AB  - OBJECTIVE: To study the effects of siRNA expression cassettes (SECs) targeting
      VEGF in vitro on cultured Hep-2 cells, the observation of the expression of VEGF,
      the screening of the best interference sequences, and the exploration of the
      application of RNA interference on tumor gene therapy in the future. METHODS: On
      the basis of the principle of target sequence of siRNA, four interference
      sequences of VEGF were designed, and the downstream gene-specific primers of the
      SECs were synthesized. The RNAi transcription kit used U6 RNA-based polymerase
      III promoter and modified terminator for high level, precise siRNA expression
      inside target cells. The Hep-2 cells was transfected in growth period of index
      with the PCR products of the four sites separately, and began to observe and
      measure the results of RNA interference in 48 hours. RESULTS: The transfected
      1366-site cells created, turned into the round shape and began to shed off,
      whereas morphology of the cells of other groups had not obviously changed.
      Performing the agarose gels electrophoresis with RT-PCR products, compared with
      the contrast groups, some cells VEGF mRNA of 1366-site were suppressed obviously,
      the ratio of OD was 0. 05 while the expression of VEGF of the cell of other
      groups had not obviously changed. Western blot revealed that VEGF expression was
      decreased obviously post transfection using 1366-site SECs. Flow cytometry showed
      that apoptosis rate of 1366-site transfected cells is 43%, and apoptosis rate of
      the rest three site transfected cells scarcely changed. Similar results were
      obtained in three independent experiments. CONCLUSIONS: The study suggested that
      siRNA expression cassettes (SECs) targeting VEGF 1366-site can effectively
      inhibit the growth laryngeal squamous cell carcinoma cell lines (Hep-2).

PMID- 16408727
TI  - [Correlative study of nuclear factor-kappa B activity and cytokine expression in
      chronic sinusitis].
AB  - OBJECTIVE: To investigate the correlation between nuclear factor-kappa B (NF
      kappaB) activity and cytokine expression in nasal mucosa of chronic sinusitis.
      METHODS: IL-5, IL-6 and IL-8 levels in nasal mucosa were assayed by the method of
      ELISA in 52 cases of chronic sinusitis [concomitant with allergic rhinitis (AR
      group), without allergic rhinitis (NAR group)] and 12 normal subjects. Semi
      quantitative RT-PCR and immunohistochemical staining were used to examine P50 and
      P65 subunits of NF-KB expressions and activation in nasal mucosa. The correlation
      between activities of NF-KB P50 and P65 subunits and cytokine expression was
      evaluated. RESULTS: IL-5, IL-6 and IL-8 levels in both AR and NAR groups were
      significantly increased (all P < 0.01 for AR group; P < 0.05, 0.05, 0.01,
      respectively, for NAR group, as compared with normal group), and the levels were
      much higher in AR group than that in NAR group (P < 0.01, 0.05, 0.01,
      respectively). The levels of P50 and P65 mRNA in both AR and NAR groups were
      enhanced (all P < 0.01 for AR group; all P < 0.01 for NAR group, as compared with
      normal group), and AR group had markedly greater P50 and P65 mRNA levels in
      comparison with NAR group (both P < 0.05). Immunohistochemical study revealed
      that nucleus-present rates of P50 and P65 in both AR and NAR groups were
      significantly higher than those of control group (all P < 0.01), and they were
      much greater in AR group as compared with NAR group (all P < 0.01). Pearson
      correlation analysis demonstrated that P50 and P65 nucleus-present rates were
      closely correlated with IL-6 and IL-8 levels, but not IL-5. The correlation
      coefficient was 0. 49 for P50 and IL-6, 0. 54 for P50 and IL-8, 0. 61 for P65 and
      IL-6, and 0.66 for P65 and IL-8 (all P < 0.01). CONCLUSIONS: Activation of P50
      and P65 subunits of NF-kappaB might be one of the mechanisms for induction of IL
      6 and IL-8 expression in chronic sinusitis. Concomitance of allergic rhinitis
      with chronic sinusitis further increased activities of NF-kappaB subunits, and
      further elevated IL-6 and IL-8 expression. IL-5 expression was independent of NF
      kappaB pathway in chronic sinusitis.

PMID- 16408729
TI  - [Heterogeneous mutations of Wolfram syndrome I gene responsible for low frequency
      nonsyndromic hearing loss].
AB  - OBJECTIVE: To explore the mutations of Wolfram syndrome I gene (WFS1) in families
      affected by non-syndromic low frequency sensorineural hearing loss (NS-LFSNHL).
      METHODS: Twenty eight individuals from 6 pedigrees with hereditary non-syndromic
      low frequency sensorineural hearing loss as a dominant trait and cases of control
      were collected in the present study. The coding sequence of WFS1 gene was
      amplified by polymerase chain reaction (PCR), and direct DNA sequencing was
      performed to screen the entire coding region of the WFS1 gene for mutations in
      the WFS1. RESULTS: Three heterozygous missense mutations (2016 G-->T, 2379 G-
      >4A, 2766 G-->A) in the WFS1 gene were found in two families. Mutations in WFS1
      were identified in all patients tested of the two pedigrees. None of the
      mutations was found in at least 280 control chromosomes and normal individuals of
      the families. These missense mutations affecting conserved amino acids in two
      pedigrees. CONCLUSIONS: Mutations in WFS1 are one of causes of non-syndromic low
      frequency sensorineural hearing loss, and the majority of mutations are missense
      mutations. Genetic counseling and genetic testing may be useful in the management
      of patients with this type of hearing loss.

PMID- 16408731
TI  - [Edit and evaluation of Mandarin sentence materials for Chinese speech
      audiometry].
AB  - OBJECTIVE: To edit the sentence list for mandarin speech test materials (MSTM)
      and to test their equivalence in order to use the list as routine clinical speech
      tests for evaluation of cochlear implants and hearing aids in different stages of
      the intervention and rehabilitation. METHODS: Firstly, two groups of
      professionals were set up: one for establishing the principles of the edit,
      another for experiments. The criteria to guide the selection of spoken sentences
      were as following: (1) suitable for everyday speech audiometry, esp. clinically
      usage; (2) a normal sampling of everyday spoken sentences in mandarin. Totally,
      300 sentences were selected in 30 lists for the experiment. The record cassette
      was used by a male speaker. The college students (54 persons,54 ears) with normal
      hearing participated in the equivalence test. Two statistic methods were used for
      equivalence analysis. RESULTS Through speech tests and statistic analysis, 2 sets
      with 29 lists (290 sentences) were selected as our equivalent lists for further
      evaluation and clinical trial. CONCLUSIONS: By setting up the strict criteria of
      selecting sentences, speech test method and statistic analysis, 2 sets of 29
      lists (290) sentences were chosen as our speech evaluation materials, but it was
      necessary for further analysis in different laboratories and clinics. The
      sentence lists should also get used for hearing impaired subjects, hearing aid
      users and cochlear implant recipients.

PMID- 16408730
TI  - [Diagnostic methods and clinic application for mtDNA A1555G and GJB2 and SLC26A4
      genes in deaf patients].
AB  - OBJECTIVE: To establish the method of clinic genetic testing for common deaf
      genes such as mtDNA nt1555, GJB2 gene and SLC26A4 (Pendrin's syndrome gene, PDS)
      gene. METHODS: Three hundred and sixty seven sporadic patients with hearing loss
      from out-patient department of General Hospital of Chinese People's Liberation
      Army, 60 patients with history of maternal inherited hearing loss from 27 family,
      20 congenital deaf patients from special educational school for deaf and dumb, 3
      deaf patients with enlarged vestibular aqueduct (EVA) confirmed by CT scan, 50
      control individuals with normal bone conductive hearing were analyzed. The
      genetic testing kit for mtDNA A1555G mutation was used to detect mtDNA A1555G
      mutation. The whole gene sequencing were accomplished in 20 congenital deaf
      patients. In 3 patients with EVA, fragments covering all exons of PDS gene were
      analyzed by denatured high productive liquid chromatogram and special exons were
      sequenced when DHPLC showed abnormal wave patterns of amplicons covering these
      exons. RESULTS: Fifty nine patients from 26 family and 5 sporadic patients were
      found to carry mtDNA A1555G mutation. Among 20 congenital deaf patients, 2 cases
      were found to have homozygous GJB2 235 del C mutation, 1 case had compound 235del
      C and 299-300 del AT mutation. Other 2 cases carried heterozygous 109 A-G
      mutation. Among 3 patients with EVA, 1 case was found to have heterozygous PDS
      G316X mutation and other 2 cases had homozygous 919-2 A-G mutation. CONCLUSIONS
      Genetic testing for deafness is feasible procedure with remarkable clinic
      significance.

PMID- 16408732
TI  - [Cervical lymph node metastasis of hypopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the characteristic of cervical lymph node metastasis of
      hypopharyngeal carcinoma and its influence to the prognosis. METHODS: One hundred
      and eight hypopharyngeal carcinoma patients who accepted treatments in the 1st
      Affiliated Hospital of China Medical University from 1985 to 2000 were reviewed
      retrospectively. All of them accepted surgical treatment without pre-operative
      chemotherapy or radiotherapy. Stage was made according to the standard of
      International Union Against Cancer (UICC) in 1992. Specimens of the patients were
      carefully examined to confirm the primary site of the tumor and the distribution
      of cervical lymph node metastasis. Pathological differentiations of the tumor
      were classified into high, middle and low category. Kaplan-Meier method was used
      to estimate the 3rd, 5th years survival. RESULTS: The rates of lymph node
      metastasis of was 45.8% for patients with TI and T2 disease, 79.8% for those with
      T3 and T4, and 75.0% (81/108)for the whole patients(P < 0.05). Patients with
      pyriform sinus cancer occupied 92.6% (100/108) of all the cases. Cervical lymph
      node metastasis rate of pyriform sinus cancer and posterior pharyngeal wall
      cancer were 74. 0% and 87. 5% respectively (P > 0.05). Cervical lymph node
      metastasis rate of patients with the high, middle and low differentiation tumor
      were 72. 2% , 67.6% and 85.7% respectively (P > 0.05). The 3rd and 5th years
      survival rates of all patients were 67.53% and 29.87% respectively. The
      occurrence of cervical lymph node metastasis was 76.5% in the level II and III,
      and 8.6% in the level V and VI. CONCLUSIONS Cervical lymph node metastasis rate
      of hypopharyngeal carcinoma is high. Cervical lymph node metastasis was one of
      the most significant prognostic factors of hypopharyngeal carcinoma. With the
      increase of the cervical node metastasis, the 3rd and 5th years survival of the
      patients declined gradually.

PMID- 16408733
TI  - [Expression of beta-defensins in human nasal mucosa and its implication].

PMID- 16408734
TI  - [Lymphocyte study of mucosa of lacrimal drainage system].

PMID- 16408735
TI  - [Expression of obese receptor in oropharynx tissue in obstructive sleep apnea
      hypopnea syndrome].

PMID- 16408736
TI  - [One case of inflammatory pseudotumor in middle ear].

PMID- 16408737
TI  - [Treatment of cranio-nasal-orbital tumor].

PMID- 16408738
TI  - [Radiofrequency for hypertrophic tonsil and turbinate reduction in children].

PMID- 16408739
TI  - [One case of anti-phospholipid syndrome resembling facial malignant granuloma].

PMID- 16408740
TI  - [Epidemiology of hearing impairment].

PMID- 16408741
TI  - [Phonosurgery and related specialties].

PMID- 16408742
TI  - [Peri-operative irradiation for advanced stage of head and neck cancer].

PMID- 16408743
TI  - [Clinical observation of sensorineural hearing loss in patients suffering from
      nasopharyngeal carcinoma after radiotherapy].
AB  - OBJECTIVE: To study the extent and incidence of sensorineural hearing loss (SNHL)
      after radiotherapy (RT). METHODS: Twenty-eight patients with diagnosed
      nasopharyngeal carcinoma (NPC) were selected. The pure-tone audiography, auditory
      brain stem evoked response (ABR), impedance audiometry and evoked otoacoustic
      emissions (EOAE) recordings were performed before RT, 1 month, 1, 2 and 5 years
      after RT. RESULTS: At 1 month after RT, there were 7.1 and 25.7 dB increased mean
      bone conduction (BC) thresholds at speech (0.5 - 4.0 kHz) and at high frequency
      (8.0 kHz), and their BC thresholds were statistically significant increase than
      those before RT, respectively (P < 0.001). At 1 year after RT, there were 17.6
      and 28.1 dB increased respectively, and their thresholds were statistically
      significant increase than those at pre-irradiation (P < 0.001). There were also
      significant increases in thresholds than those at 1 month of post-irradiation (P
      <0.001 or P < 0.05). At 2 years after RT, 21 and 27.4 dB were increased at
      respective those two frequencies, and there was a statistically difference only
      at speech frequencies when compared with those at 1 year after RT (P < 0.05). At
      5 years after RT, 26.7 and 35.8 dB were increased at these two frequencies, and
      there were significant increases in threshold than those before, 1 month, 1 and 2
      years after RT, respectively (P < 0.001). From 1 month to 5 years after RT, 37.
      5% to 94. 7% of ears had a BC hearing threshold of at least 15 dB losses at
      speech frequency, whereas the percentage at high frequency was 85.4 to 97.4%. Up
      to 63.2% and 73.7% of ears had 30 dB SNHL at least at speech and high frequency,
      respectively. Furthermore, the degree of mean threshold loss was greater at high
      frequency than at speech frequency. The mean value of wave I, III and V latency,
      and I -V interpeak latency intervals of ABR had no significant difference between
      at 1 month after RT and before RT (P > 0.05). The wave I , III and V latency, and
      I - V interpeak latency intervals at 1 year and 2 years were significantly
      prolonged when compared with those before and 1 month after RT (P < 0.05), but
      there were no significant difference between 1 year and 2 years after RT (P >
      0.05). The wave I, III and V latency, and I -V interpeak latency intervals at 5
      years after RT were also significantly longer than those before RT (P < 0.001).
      There were significant difference in wave I , III and V latency (P < 0.05), and
      no significant difference in wave I - V interpeak latency intervals (P > 0. 05)
      between 5 years after RT and 1 year or 2 years after RT. Seven of 10 ears at 1
      year after RT and 4 of 7 ears at 5 years after RT had normal EOAE, but they all
      had abnormal ABR response. CONCLUSIONS: SNHL in NPC patients start soon after
      completion of RT, especially more commonly in high frequency. The incidence and
      the extent of hearing loss are increased with time of follow-up. The hearing
      impairment could occur in the cochlea and/or the retrocochlear auditory pathway,
      which show that the sensitivity of radiation damage may be different in different
      patient and anatomic site of auditory system.

PMID- 16408744
TI  - [Salvage surgical approach for patients with post-radiation local recurrent
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate salvage surgical approaches and efficacy for post
      radiation local recurrent nasopharyngeal carcinoma (NPC). METHODS: Thirteen
      patients with post-radiation local recurrent NPC underwent salvage surgical
      treatment by routes as transpalatal approach, nasal medial swing approach,
      maxillary swing approach and infratemporal fossa approach. All cases were
      followed up for 2 to 5 years. Analysis was done on the indications and efficacy
      of these 4 different approaching routes. RESULTS: No immediate operative
      complications occurred for all these 13 cases. Four patients with T1 and T2a
      operated via transpalatal approach and nasal medial swing approach survived more
      than 3 years. Five patients with T2b and T3 operated via maxillary swing
      approach. Among them, two patients died at second and 24th month after operation,
      one survived with tumor and died at 13rd month after operation, two were alive
      free of tumor for 2 and 4 years after operation. Four patients with T4 operated
      via infratemporal fossa approach. Among them, three died in 1 year, one was alive
      free of tumor for 2 years. CONCLUSIONS: Surgical approaches were decided by a
      comprehensive consideration of recurrent tumor site and invasive range to achieve
      the best operative site exposure with minimal traumatic damage.

PMID- 16408745
TI  - [Clinicopathological features and prognosis of postirradiation osteosarcoma in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: Post irradiation osteosarcoma (PIOS) in patients with nasopharyngeal
      carcinoma (NPC) is rare and a potential late complication of radiation. We
      investigate its clinicopathological features and prognosis. METHODS: 426 cases of
      bone sarcomas in Cancer Center of Sun Yat-sen University, China between 1964 and
      2003 were reviewed retrospectively. Fifteen patients were determined to have PIOS
      after radiation of NPC. Its prevalence rate, onset time, site, image features,
      and treatment were described. Kaplan-Meier analysis was used to determine the
      relative prognostic factors. RESULTS: In 12 patients undertaken radical surgery,
      one patient had residual tumor and six patients presented tumor recurrence five
      to 19 months (mean of nine months) after surgery. All patients survived seven to
      41 months with a mean of 18 months. The one-year and two-year survival rates were
      60% and 24% respectively. Female patients with large area of tumor bone formation
      in images had better survival than male patients without or few tumor bone
      formation. Age, radiation dosage, onset time of PIOS, tumor size, and treatment
      were probably not significant factors to prognosis. CONCLUSIONS: PIOS in patients
      with NPC is a high malignant disease and often has poor prognosis. Surgery with
      pre-and post-operative chemotherapy might be a way to improve its survival.

PMID- 16408746
TI  - [Transnasal surgery in cavernous hemangioma ectomy of orbital apex].

PMID- 16408747
TI  - [Second primary tumor of tongue after nasopharynx carcinoma radiotherapy: report
      of 53 cases].
AB  - OBJECTIVE: To investigate the clinical characteristics of second primary tumor of
      tongue after nasopharyngeal carcinoma (NPC) radiotherapy and the prognostic
      factors of patients. METHODS: Fifty-three cases with second primary tumor of
      tongue after NPC radiotherapy, presenting to Cancer Centre, Sun Yat-sen
      University from Jan. 1st 1975 to Dec. 31st 2000 were analyzed retrospectively
      with regard to mortality and survival rate (Kaplan-Meier method); A multivariate
      analysis was performed in these patients with Cox proportional hazard model.
      RESULTS: Forty of 53 patients died. Among them,37 died of second primary tumor of
      tongue, 2 of recurrence of NPC, 1 of perioperative period. The overall 5-year and
      10-year survival rate of 51 patients receiving therapy were 41.64% and 35.69%
      respectively. The subsites of tumor were: tip 0, margin 26 (49.06%), ventral
      lateral 8 (15.09%) and dorsal aspect 19 (35.85%). Eighteen cases had recurrence
      of second primary tumor of tongue (33.96%) ; Six (11.32%) cases had clinical
      lymph node metastasis from second primary tumor of tongue and 3 (5.66%) had
      pathological lymph node metastasis; The univariate analysis showed the major
      prognostic factors influencing survival of these patients were tumor size,
      clinical TNM stage at presentation; Using multivariate analysis, risk factors
      that independently influence survival were clinical and pathological stage and
      the interval between two tumors. CONCLUSIONS: The clinical and pathological stage
      and the interval between two tumors are the prognostic factors for second primary
      tumor of tongue after NPC radiotherapy.

PMID- 16408748
TI  - [Morphological and functional alterations of ear in lysosomal neuraminidase gene
      deficient mouse].
AB  - OBJECTIVE: To observe the alterations of the auditory function and morphology of
      the ear in the mouse sialidosis models which has been generated by targeted
      deletion of lysosomal neuraminidase gene (Neul) and closely resembled the
      phenotypes in corresponding human conditions, and to explore pathophysiological
      mechanisms of hearing impairment. METHODS: Neul homozygous (Neul -/-) mice at 3
      weeks, 2 and 4 months of age, and their wildtype littermates (Neu1 +/+) were
      examined for auditory thresholds through auditory brainstem responses (ABR) to
      click, 8, 16, and 32 kHz stimuli. Morphological analyses in ears were performed
      by series temporal bone section and light microscopy. RESULTS: Neul -/- mice at 3
      weeks of age showed an elevated ABR threshold, 50-55 dB above those of Neul +/+
      mice. Up to 2 and 4 months of age, their thresholds were further elevated for 60
      68 dB. There were distinct pathological changes of middle and inner ear of 3
      weeks of age in Neul -/- mice, especially at 2-4 months of age there were
      significant cerumen occlusion in the external auditory canal and severe otitis
      media. Vacuolation associated with lysosomal storage was observed within ossicles
      and cochlear bone cells, stria vascularis cells, spiral ganglion neurons and
      macrophages, spiral limbus, spiral prominence, Reissner's membrane cells, and the
      mesothelial cells of the perilymphatic scala and basilar membrane, but not within
      the organ of Corti. Vestibular ganglion neurons, hair cells and supporting cells
      in cristae and maculae also showed vacuolation. CONCLUSIONS: The deficiency of
      lysosomal neuraminidase may result in a serious hearing loss and morphological
      alterations of ear. The external auditory canal obstruction, otitis media and
      ossicle changes may cause conductive hearing loss, and the defects in lysosomal
      storage of neurons, stria vascularis, spiral limbus, Reissner's membrane and
      basilar membrane cells may contribute to sensorineural deafness.

PMID- 16408749
TI  - [Modulation of gamma-aminobutyric acid receptor on medial vestibular nucleus
      neurons in vivo].
AB  - OBJECTIVE: To investigate modulation of gamma-aminobutyric acid (GABA) and its
      receptors on medial vestibular nucleus neurons in vivo. METHODS: Twenty-six male
      Wistar rats were used. gamma-aminobutyric acid, bicuculline (BIC, gamma
      aminobutyric acid A receptor antagonist) and 2-hydroxysaclofen (SAC, gamma
      aminobutyric acid B receptor antagonist) were microiontophoresed on medial
      vestibular nucleus (MVN) neurons to determine the effects of gamma-aminobutyric
      acid and its antagonists on the neuronal firing rates of medial vestibular
      nucleus in rats in vivo. RESULTS: Microiontophoretic application of y
      aminobutyric acid at 10, 30, 50 nA electric current produced inhibitory responses
      on 42 MVN neurons, these responses were dose-dependent decreases, firing rates (x
      +/- s) of MVN neurons decreased form (14.8 +/- 5.6) times/s to (8.7 +/- 3.4)
      times/s, (4.1 +/- 1.6) times/s and (2.2 +/- 1.1) times/s respectively;
      microiontophoretic application of bicuculline in 37 MVN neurons, 86.5% (32/37)
      neurons produced excitatory responses, 13.5% (5/37) neurons didn't response,
      firing rates of MVN neurons increased form (15.3 +/- 6.3) times/s to (16.8 +/-
      7.1) times/s, (25.9 +/- 10.1) times/s and (32.7 +/- 11.3) times/s respectively at
      10, 30, 50 nA electric current, which were dose-dependent increases, and the
      inhibitory responses of gamma-aminobutyric acid on MVN neurons were blocked by
      bicuculline completely; however, microiontophoretic application of 2
      hydroxysaclofen didn't produced responses as bicuculline did. CONCLUSIONS:
      Modulation of gamma-aminobutyric acid on medial vestibular nucleus neurons was
      mediated by y-aminobutyric acid A receptor in vivo.

PMID- 16408750
TI  - [Inhibition of salicylate on potassium channels in rat inferior colliculus
      neurons].
AB  - OBJECTIVE: To understand what role of the transient outward potassium channels
      and the delayed rectifier potassium channels play in the mechanism of salicylate
      induced tinnitus. METHODS: The effects of salicylate on the transient outward
      potassium channels and the delayed rectifier potassium channels in freshly
      dissociated inferior colliculus neurons of rats were studied, using the whole
      cell voltage clamp method. RESULTS: Salicylate blocked the transient outward
      potassium current (I(K(A and the delayed rectifier potassium current (I(K(DR in
      concentration-dependent manner (0.1-1 mmol/L). The IC50 values for the blocking
      action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mmol/L,
      respectively. At a concentration of 1 mmol/L, salicylate did not shift the
      activation and inactivation curves of I(K(A)), but significantly shifted the
      activation and inactivation curves of I(K(DR)) negatively by approximately 11 mV
      and 24 mV. CONCLUSIONS: Salicylate inhibits both I(K(A)) and I(K(DR)) in rat
      inferior colliculus neurons but only significantly affects the activation and
      inactivation kinetics of I(K(DR)). Effects of I(K(A)) and I(K(DR)), especially
      I(K(DR)), by salicylate may play an important role in salicylate-induced
      tinnitus.

PMID- 16408752
TI  - [Structure of nasal cavity and characters of airflow].
AB  - OBJECTIVE: To study the airflow in nasal cavity by reconstructing 20 volunteers'
      nasal cavity models and numerical simulation of the flow field in these nasal
      cavity models. METHODS: Based on the data from the CT images, 20 volunteers'
      nasal cavity models were reconstructed by the method of surface rendering. The
      flow field in these three-dimensional models were simulated with finite element
      method. Some of these volunteers were tested by means of acoustic rhinometry and
      the test results recorded. Comparisons were performed for the curves from
      acoustic rhinometry and the results of numerical simulations. The simulation
      results were explained with the fluid network theory. RESULTS: The airflow
      distribution in the nasal cavity model could be acquired from the simulation
      results of the velocity plot. Main airflow would pass through the common nasal
      meatus in which flux accounted for 50% - 77% of overall flux. The pressure value
      at any point in the nasal cavity model could be obtained from the results of the
      pressure plot. The nasal airway resistance in the region of limen nasi accounted
      for 50% - 65% of overall nasal airway resistance. Comparing the test results with
      the simulation results the relation could be understood between the change of the
      cross-section area of nasal cavities and the plot of numerical simulation results
      of velocity and pressure in airflow field in the nasal cavity models.
      CONCLUSIONS: Comparing the simulated results of the 20 volunteers' nasal cavity
      model it can be concluded that the distribution of airflow in nasal cavities is
      not stationary. The differences among everybody's nasal cavity structure lead to
      the different airflow distribution in the nasal cavities.

PMID- 16408751
TI  - [Inhibition of eIF families expression and angiogenesis for human laryngeal
      carcinoma by elemene administration].
AB  - OBJECTIVE: To investigate the inhibitory effect of elemene on laryngeal carcinoma
      (Hep-2 cells) xenograft growth in nude mice and its mechanisms, and to explore
      the relationship between the expression of eukaryotic initiation factor families
      (eIF4E & eIF4G) and angiogenesis factors (bFGF & VEGF) after the administration
      of elemene. METHODS: Human laryngeal carcinoma cells from Hep-2 cell strain were
      transplanted subcutaneously to BALB/c-nu/nu nude mice to produce tumors (42 nude
      mice were separated into seven groups to be treated by intraperitoneal
      injection). The tumor volume, tumor weight and tumor inhibition rate were
      evaluated, the expression of eIF4E, eIF4G, bFGF, VEGF and microvessel density
      were estimated by paraffin-embedded sections of seven groups' tumor samples
      analyzed utilizing immunohistochemical streptavidin peroxidase technique.
      RESULTS: Elemene could inhibit the tumor growth in vivo. A significant
      suppression of tumor growth was observed when the dosage was increased. The tumor
      inhibition rates (IR) of elemene 50 mg/kg, 100 mg/kg and 200 mg/kg treated group
      were 5.2% , 41.7% and 50. 5% respectively. The IR of 100 mg/kg elemene (41.7%)
      was not significantly different with that of 3 mg/kg cisplatin (44.6%), and the
      IR of the drug combination (100 mg/kg elemene + 3 mg/kg cisplatin) was 51.2%.
      Compared with control groups the protein expression of eIF4E, eIF4G, bFGF and
      VEGF were significantly inhibited by elemene (P < 0.05), and the microvessel
      density in elemene treated groups decreased (P < 0.05). The tumor inhibition rate
      of combined elemene 100 mg/kg and cisplatin 3 mg/kg was 51.2%. CONCLUSIONS:
      Elemene could inhibit the subcutaneous plantation of human laryngeal carcinoma in
      nude mice and its mechanism may be associated with inhibited expression of eIF
      families and angiogenesis factors. The combination of elemene and cisplatin could
      promote the synergistic effect on chemotherapy in the target tumor cells.

PMID- 16408753
TI  - [Clinical study of extranodal NK-T cell lymphoma-nasal type].
AB  - OBJECTIVE: To discuss how the diagnosis, misdiagnosis and different treatment
      modalities affect the prognosis of the patients with extranodal NK-T cell
      lymphoma-nasal type. METHODS: A retrospective study was made on the clinical
      characteristics, treatment modality, short-term effect, and survival rate of 68
      patients with extranodal NK-T cell lymphoma-nasal type. Among them,60 patients
      staged I(E) were subdivided into single therapy group of 20 cases( radiation
      therapy 9 cases, chemotherapy 11 cases) and combined therapy group of 40 cases (9
      cases with radiation therapy + chemotherapy, 12 cases with chemotherapy +
      radiation therapy,19 cases with chemotherapy + radiation therapy + chemotherapy).
      Eight patients staged IV(E) included 3 cases with radiation therapy alone and 5
      cases with chemotherapy and radiation therapy. RESULTS: The rate of misdiagnosis
      of whole group is 66. 2% (45/68), and the rate of misoperated patients accounted
      for 52. 9% (36/68). The CR rate of radiation therapy was 94. 4% (17/18) for
      limited disease in I(E) group compared 61.9% (26/42) for out-cavity disease in
      I(E) group, of which the difference is significant (P =0. 012). The 1-years, 3
      years and 5-years survival rate of the I(E) intra-cavity group were 100%, 77.8%,
      59.8%, and those of ex-cavity group were 80.1%, 48.5% and 14.6%, respectively.
      The 1, 3 and 5-years survival rate of IV(E) group were 17.5%, 0.0% and 0.0%. The
      difference of survival was significance among the above 3 groups (P = 0. 000).
      The 1, 3, 5-years survival rate of 60 I(E) patients with single therapy were
      68.4%, 22.8% and 7.6% respectively; and that of combined therapy group were
      94.9%, 81.1% and 52.4% respectively, which was significant difference (P = 0.
      000). The survival difference among the radiation therapy + chemotherapy group,
      chemotherapy + radiation therapy group and chemotherapy + radiation therapy +
      chemotherapy group were not significant (P = 0.088). CONCLUSIONS: The early
      clinical manifestation of extranodal NK-T cell lymphoma-nasal type is not
      typical,which is easy to be misdiagnosed and mistreated. Early therapy is the
      key,which can achieve good location control. Diseased stage I(E) out-cavity and
      above should be treated with combined therapy.

PMID- 16408754
TI  - [Comparative study of the parameters related to type I thyroplasty measured by
      laryngeal specimens and computed tomography].
AB  - OBJECTIVE: To determine the consistence of the parameters related to type I
      thyroplasty measured by laryngeal specimens and CT scan. METHODS: The related
      parameters of 50 laryngeal specimens (unilateral) obtained following total
      laryngectomy were measured postoperative immediately, and compared with those
      measured by spiral CT scan with multiple plain reconstructive (MPR) technique
      preoperatively. Comparative results were analyzed to evaluate the statistical
      significance between these two methods. RESULTS: There were no significant
      statistical differences among the 6 parameters between two methods (P > 0.05),
      and the results (x +/- s) measured by CT scan and laryngeal specimens showed that
      the length of the thyroid notch to the inferior thyroid border were (20.7 +/-
      1.7) mm and (20.6 +/- 1.7) mm; the length of the vocal cord were (17.3 +/- 1.8)
      mm and (17.3 +/- 1.8) mm; the length of the oblique line were (28.6 +/- 3.2) mm
      and (29.1 +/- 2.7) mm; the length of the presumptive horizontal line were (26.2
      +/- 2.0) mm and (26.2 +/- 2.0) mm; the endolaryngeal vertical length of the
      anterior of the vocal cord to the presumptive horizontal line were (4.5 +/- 0.6)
      mm and (4.5 +/- 0.7) mm; the endolaryngeal vertical length of the vocal process
      to the presumptive horizontal line were (10.8 +/- 1.1) mm and (10.9 +/- 1.1) mm,
      respectively. As a result, the endolaryngeal anterior and posterior width of the
      wedge inserted in the thyroid cartilage were 4 - 5 mm and 8 - 9 mm respectively.
      CONCLUSIONS: MPR technique of spiral CT scan is able to design the size of the
      window and the prosthesis of type I thyroplasty preoperatively, which was
      testified to be a precise and reliable method to measure the larynx.

PMID- 16408755
TI  - [Re-operation for thyroid carcinoma].
AB  - OBJECTIVE: To evaluate the results of re-operation of thyroidectomy for patients
      of thyroid carcinoma. METHODS: 268 patients of thyroid carcinoma received
      completion thyroidectomy were retrospectively reviewed from 1984 to 2000. There
      were 59 males and 209 female cases. 256 cases had received nodule enucleating or
      partial thyroidectomy in other hospitals and 12 cases had unilateral subtotal
      thyroidectomy in this hospital. The types of reoperation were: Total
      thyroidectomy for bilateral thyroid carcinoma (6 cases); expand isthmectomy for
      isthmus carcinoma (1 case). Lobectomy plus isthmectomy for unilateral disease
      (261) Simultaneous neck dissections were performed in 196 cases. Among them, 94
      cases had classical neck dissection, 102 cases had modified neck dissection.
      RESULTS: Pathological results confirmed that there were 78 cases with residual
      thyroid carcinoma. The rate of residual carcinoma was 29. 1% (78/268). There were
      95 cases with lymphnode metastasis. The rate of lymphnode metastasis was 48.5%
      (95/196). The rate of recurrent laryngeal nerve injury was 1.1% (3/268). The 5
      year and 10-year survival rates of patients were 94. 0% (251/267) and 85. 2%
      (127/149) respectively. CONCLUSIONS: The residual carcinoma of completing
      thyroidectomy was high. Therefore re-operations of thyroid in selected cases were
      necessary.

PMID- 16408756
TI  - [Role of clonality analysis by X-chromosome inactivation in the diagnosis of
      cervical lymph node occult micrometastasis from squamous carcinoma of the head
      and neck].
AB  - OBJECTIVE: To investigate the role of clonality analysis by X-chromosome
      inactivation in the diagnosis of cervical lymph node metastasis from squamous
      carcinoma of the head and neck. METHODS: Twenty cases of clinical NOM0 squamous
      carcinoma of the head and neck with either pathologically confirmed or suspected
      occult micrometastasis in the cervical lymph node were recruited. Interested DNA
      samples were procured through tissue microdissection and one-step proteinase K
      digestion, and the clonality analysis was carried out by means of restriction
      enzyme digestion and amplification of human androgen receptor markers (HUMURA) to
      check out the status of X-chromosome inactivation. The clonal origin of the
      primary tumor cells and the interested cell clones in the cervical lymph node was
      traced by X-chromosome inactivation, and the diagnosis of cervical lymph node
      micrometastasis was either confirmed or ruled out. RESULTS: Tumor cells from both
      primary and metastatic lesions were monoclonal and identical in clonal origin in
      10 patients with pathologically confirmed cervical lymph node metastasis, whose
      metastatic tumor cells expressed EGF receptor. For 10 patients with suspected
      micrometastasis in the neck nodes, whose focused lesions did not expressed any
      EGF receptor protein by immunohistochemistry, the identical and monoclonal origin
      between the primary tumor and the suspected metastatic lesion in the neck node
      was confirmed in 6 patients, and the polyclonal origin of the neck node lesions
      was revealed in other 4 patients. The diagnosis of micrometastasis in the neck
      node was thus ascertained in 6 and ruled out in 4 suspected cases. CONCLUSIONS:
      Examination of X-chromosome inactivation pattern is a useful method for
      identification of the neck node occult micrometastasis from squamous carcinoma of
      the head and neck.

PMID- 16408758
TI  - [Expression of hyaluronan in laryngeal carcinoma].

PMID- 16408757
TI  - [Expression of bcl-2 in rat nasal mucosae with experimental allergic rhinitis].

PMID- 16408759
TI  - [A case of transnasal endoscopic repair of CSF caused tension pneumocrania].

PMID- 16408760
TI  - [Diagnostic value of MSCT in nasal septum fracture].

PMID- 16408761
TI  - [Laryngeal reconstruction with radial forearm free flap after total
      laryngectomy].

PMID- 16408762
TI  - [Problem on measuring quality of life in Chinese Journal Otorhinolaryngology].

PMID- 16408763
TI  - [Role of radiotherapy in the treatment of head and neck carcinoma].

PMID- 16408764
TI  - [Involvement of amygdala in the emotional processing of pain].
AB  - This review will discuss the recent studies about the role of amygdala in pain
      processing. Pain has a strong emotional component, and the amygdala plays a major
      role in emotional behaviours. An increasing number of evidences implicated the
      amygdala in the process of pain encoding and modulation. Amygdala may integrate
      the nociceptive information from the spinal cord and the trigeminal nucleus with
      information of other sensory modalities from thalamic and cortical areas, and
      generate the emotional reactions and the behavioral responses of pain. On the
      other hand, amygdala may also be involved in pain modulation through connections
      with periaquiductal gray (PAG) , rostral ventromedial medulla (RVM), and other
      brain stem areas.

PMID- 16408765
TI  - [Cancer chemotherapy and drug metabolism enzyme].
AB  - Drug metabolism enzymes (DME) play a significant role in drug detoxification and
      activation, which exert important effect on drug efficacy and sensitivity to
      toxicity. There is difference in expression and activity of DME between in tumor
      tissue and in non-tumor tissue. DME related with tumor chemotherapy are
      cytochrome P450 (CYP), glutathione-S-transferase (GST), uridine diphospho
      glucuronosyltransferase (UGT), thiopurine methyltransferase (TPMT) and
      dihydropyrimidine dehydrogenase (DPD). The enzymes above are inducible and
      genetic polymorphic, thus with variable activity in individuals.

PMID- 16408766
TI  - [Role of cGMP-dependent protein kinase in the cardiovascular system].
AB  - cGMP-dependent protein kinase (PKG) is the major intracellular receptor for
      cyclic guanosine monophosphate (cGMP). Two forms of PKG, PKG-I and PKG-II, occur
      in mammalian tissues. PKG may mediate nitric oxide-cGMP-induced vasodilation
      through decreasing intracellular calcium concentration by the activation of
      calcium-activated potassium channel on the cell membrane and phosphorylation of
      phospholamban (PLB) and IP3 receptor-associated PKG-I substrate (IRAG) on the
      sarcoplasmic reticulum. PKG may also decrease the sensitivity of myosin to
      calcium by stimulating the activity of myosin light chain phosphatase and by
      inhibiting Rho kinase activity. PKG plays an important role in regulating the
      gene expression, phenotype, and proliferation of vascular smooth muscle cells.
      PKG activation inhibits platelet aggregation and myocardial hypertrophy. Recent
      studies indicate that the alternations of PKG expression and activity are closely
      related with the pathogenesis of atherosclerosis, restenosis, hypertension,
      hyperlipemia as well as nitrate tolerance.

PMID- 16408767
TI  - [Non-genomic actions of steroids: mechanism and significance].
AB  - It has been demonstrated that all steroids can exert their actions by rapid non
      genomic effects. Different steroids have different non-genomic mechanism. And
      there always occurs some new mechanism after some time. Now we review the non
      genomic mechanism and significance of steroids.

PMID- 16408768
TI  - [Activation mechanisms of protein kinase Czeta and its cellular function].
AB  - The zeta isotype of protein kinase C (PKCzeta) is a member of the atypical PKC
      subfamily and has been widely implicated in the regulation of cellular functions.
      PKCzeta, as an important message molecular, is involved in many intracellular
      signaling pathways, such as the mitogen-avtivated protein kinase (MAPK) cascade,
      transcriptional factor NF-kappaB activation, ribosomal S6-protein kinase
      signaling and so on. Increasing evidence from studies support the concept that
      the activation mechanisms of PKCzeta are tissue/cell specific. The understanding
      of the mechanisms underlying PKCzeta-mediated control of intracellular signaling
      is beginning to provide important insightsinto the roles of PKCzeta in various
      cells.

PMID- 16408769
TI  - [Tissue transglutaminase and renal fibrosis].
AB  - Tissue transglutaminase (tTG), an enzyme which can catalyze the posttranslational
      modification of proteins, is widely distributed and plays an important role in
      both physiological and pathological processes. More recently, tissue
      transglutaminase has been believed to participate in tissue fibrosis. Cross
      linked extracellular matrix proteins by tissue transglutaminase are stable and
      highly resistant to proteolytic degradation, thus lead to accumulation of the ECM
      proteins in tissue fibrosis. This review summarizes the important features of
      this multifunctional enzyme and particularly introduces the correlation between
      tTG and renal fibrosis.

PMID- 16408770
TI  - [Research progress of Ape/Ref-1 and central nervous system diseases].

PMID- 16408771
TI  - [IGF-1 alternative splice isoforms: mechano growth factor].

PMID- 16408772
TI  - [The mechanisms of antifungal drug resistance and novel antifungal agents].

PMID- 16408773
TI  - [Mechanism of pain anticipation].

PMID- 16408774
TI  - [Mechanisms of delta-opioids cardioprotective effects in ischemia and its
      potential clinical applications].

PMID- 16408775
TI  - [Progress in the study of ATP-binding cassette transporter A1].

PMID- 16408776
TI  - [The role of Rho/Rho-kinase pathway in smooth muscle contraction].

PMID- 16408777
TI  - [Mechanisms of regulation of endothelial nitric oxide synthase].

PMID- 16408778
TI  - [Cardiovascular functions of urocortin].

PMID- 16408779
TI  - [Advances on the studies of integrin mediated signaling].

PMID- 16408780
TI  - [Progress in caveolae and its proteomic research].

PMID- 16408781
TI  - [Research progress on M-type potassium channel].

PMID- 16408782
TI  - [Role of gap junction in mouse ovarian follicle development].

PMID- 16408783
TI  - [Store-operated channels on smooth muscle cells].

PMID- 16408785
TI  - [The behavior-neuroendocrine effects on the development of social behaviors].

PMID- 16408784
TI  - [Hepcidin, a key iron-regulatory hormone with antimicrobial activity].

PMID- 16408786
TI  - [DNA radiation damage and p53].

PMID- 16408787
TI  - Identification of a pharmacophore of SKCa channel blockers.
AB  - Small conductance calcium-activated potassium channels (SK) are widely expressed
      throughout the central nervous system (CNS) and the periphery. Three subtypes of
      SK channels have so far been identified in different parts of the brain.
      Activation of the SK channels by a rise in intracellular calcium leads to the
      hyperpolarisation of the membrane, reducing cell excitability. Blocking the SK
      channels might be beneficial in the treatment of depression, Parkinson's disease
      and cognitive disorders. However, few blockers of SK channels have been
      characterized. In this study, a pharmacophoric model of SK channels blockers is
      presented. It is based on a series of nonpeptidic compounds and apamin, a
      peptidic blocker. To create the pharmacophore model, the conformational space of
      nonpeptidic blockers was investigated to generate a series of distance
      constraints applied to a simulated annealing study of apamin. The resulting
      conformation was superimposed with the nonpeptidic blockers to give a
      pharmacophore.

PMID- 16408788
TI  - Lipid-lowering properties of 6-benzoyl-2(3H)-benzothiazolone and structurally
      related compounds.
AB  - Fifteen compounds derived from the 2(3H)-benzothiazolone template with an acyl
      side-chain in position-6 were evaluated for their lipid-lowering action in mice.
      Among these compounds, 6-benzoyl-2(3H)-benzothiazolone was found to be the most
      potent one both in mice models receiving a hypercholesterolemic diet (for 15
      days) or a standard diet (for 21 days). 6-Benzoyl-2(3H)-benzothiazolone compares
      favorably with fenofibrate, the standard drug, both in terms of HDL-C/Chol (High
      Density Lipoprotein-Cholesterol/Total Cholesterol) ratio and absence of liver
      hepatomegaly.

PMID- 16408790
TI  - Synthesis and preliminary in vivo evaluation of new 2-Aryl-6-methyl-1,2-dihydro
      1H-pyridin-4-ones and 2-Aryl-6-methylpiperidin-4-ols, as potential anti-amnesiant
      agents.
AB  - A revisited synthesis of 2-aryl-6-methyl-1,2-dihydro-1H-pyridin-4-ones and their
      saturated analogues 2-aryl-6-methylpiperidin-4-ols is described. A five steps
      procedure, using the sulfinimine chemistry, to prepare a key intermediate beta-(6
      chloronicotinic)-beta-amino ester is also reported. In vivo spontaneous working
      memory activity of these compounds has been investigated in the mouse. Results
      obtained with 2-(3-chlorophenyl)-6-methyl-1,2-dihydro-1H-pyridin-4-one 9b, the
      most effective derivative in this model, have been reported.

PMID- 16408789
TI  - Synthesis and antiviral activity of aryl phosphoramidate derivatives of beta-D-
      and beta-L-C-5-substituted 2',3'-didehydro-2',3'-dideoxy-uridine bearing linker
      arms.
AB  - We have previously reported the synthesis and evaluation of potent anti-human
      immunodeficiency virus compounds based on beta-D-d4T analogues bearing a tether
      attached at the C-5 position and their beta-L-counterparts. Initial study
      revealed a requirement for an alkyl side-chain with an optimal length of 12
      carbons for a weak antiviral activity. As a continuation of that work, we have
      now prepared the corresponding phosphoramidate derivatives as possible membrane
      permeable prodrugs. Phosphorochloridate chemistry gave the target
      phosphoramidates which were tested for anti-human immunodeficiency virus type 1
      activity; unfortunately, they were devoid of anti-HIV activity.

PMID- 16408791
TI  - Synthesis and evaluation of the antiproliferative activity of novel
      thiazoloquinazolinone kinases inhibitors.
AB  - The microwave-assisted synthesis of a family of 2,8-substituted
      thiazoloquinazolinones is described. The preliminary evaluation of the
      antiproliferative activity and the capacity of these molecules to inhibit CDKs
      and GSK-3 are reported. A lead compound was identified, constituting a scaffold
      from which more potent inhibitors could be designed.

PMID- 16408792
TI  - Synthesis and preliminary antiproliferative evaluation of 1,3,9
      triazacyclopenta[b]fluorene derivatives.
AB  - Novel 1,3,9-triazacyclopenta[b]fluorene-4,10-diones and 1,3,9
      triazacyclopenta[b]fluorene, analogue of ellipticine, were synthesised, and
      evaluated in vitro for their antiproliferative activity on various breast cancer
      cell lines.

PMID- 16408795
TI  - Six sigma practices. A strategy based on data is perfect fit for healthcare.

PMID- 16408794
TI  - Three-dimensional model of cytochrome P450 human aromatase.
AB  - A three-dimensional (3-D) structure of human aromatase (CYP 19) was modeled on
      the basis of the crystal structure of rabbit CYP2C5, the first solved X-ray
      structure of an eukaryotic cytochrome P450 and was evaluated by docking S
      fadrozole and the steroidal competitive inhibitor (19R)-10-thiiranylestr-4-ene
      3,17-dione, into the enzyme active site. According to a previous pharmacophoric
      hypothesis described in the literature, the cyano group of S-fadrozole partially
      mimics the steroid backbone C(17) carbonyl group of (19R)-10-thiiranylestr-4-ene
      3,17-dione, and was oriented in a favorable position for H-bonding with the newly
      identified positively charged residues Lys 119 and Arg435. In addition, this
      model is consistent with the recent combined mutagenesis/modeling studies already
      published concerning the roles ofAsp309 and His480 in the aromatization of the
      steroid A ring.

PMID- 16408796
TI  - More to store. Hospitals, health systems and health plans face the volume issue.

PMID- 16408797
TI  - The cancer care niche. Providers take matters into their own hands.

PMID- 16408793
TI  - Synthesis of reduced xanthatin derivatives and in vitro evaluation of their
      antifungal activity.
AB  - Abstract The synthesis of new xanthanolide derivatives is reported starting from
      xanthatin, a sesquiterpenic lactone isolated from Xanthium macrocarpum
      (Asteraceae). In vitro evaluation of their antifungal activity has been
      investigated.

PMID- 16408798
TI  - Pervasive access via WLAN. An upgraded infrastructure connects current facilities
      and anticipates the future.

PMID- 16408799
TI  - [Biopartitioning micellar chromatography: its application in evaluating drug
      membrane transport and activity].

PMID- 16408800
TI  - [Heparanase: target for cancer metastatic therapy].

PMID- 16408801
TI  - [Structure and spectral characteristics of Diels-Alder type adducts from Morus].

PMID- 16408802
TI  - [The erosion behaviour of matrix tablets using polyethylene oxide matrices as
      hydrophilic polymer].
AB  - AIM: To study the erosion behaviour during dissolution of matrices using
      different molecular weight polyethylene oxide (PEO) as hydrophilic polymer.
      METHODS: PEO hydrophilic matrix tablets with no added drug and excipients were
      prepared by direct compression method. The erosion rates of matrices comprised of
      pure or blending PEO polymers were evaluated in distilled water at (37 +/- 0.5)
      degrees C with rotating rate of 50 r x min(-1). The relationship between PEO
      molecular weight and erosion rate of matrices was investigated by experimental
      and mathematical model methods. RESULTS: The gravimetric erosion experimental
      results indicated that the power-law relationship which relates the polymer
      erosion rate and weight average molecular weight: k infinity (M(w)) -1.30 4 was
      proved to have great potential utility in predicting the degree of polymer
      erosion of matrices comprised of either intermediate molecular weight (97. 98 x
      10(4) - 553. 36 x 10(4)) or blends of lower and higher molecular weight polymers.
      Based on the semiempirical equation for mass transfer rate: Jp = (fp < Dp > (2/3)
      v (-1/6) omega (1/2)) C(p,dis), a theoretical mathematic model was developed for
      describing the relationship between PEO erosion rate and PEO weight average
      molecular weight: Jp infinity M(-1.241), where the exponent of -1. 241 was very
      close to the exponent of - 1. 130 4 obtained from practical determination.
      CONCLUSION: PEO was proved to be a good candidate of hydrophilic polymer and
      appeared to have great potential for controlled release applications. The
      mathematic model presented together with the utilization of the erosion behaviour
      discussed in our study could provide a guide line to predict the degree of
      polymer erosion for other intermediate polymer grades and / or mixture of the
      polymers utilized in this study, which could play an active role in designing PEO
      hydrophilic sustained delivery systems.

PMID- 16408803
TI  - [In vitro and in vivo stability of 9-nitrocamptothecin lactone form in rats].
AB  - AIM: To investigate the in vitro and in vivo stability of 9-nitrocamptothecin
      lactone form in rat plasma. METHODS: The specific and accurate HPLC method was
      developed for quantifying 9-nitrocamptothecin lactone form and the total lactone
      and carboxylate forms simultaneously. By using of this method, the ratios of
      lactone form to the total in rat plasma at different time were determined in
      vitro and in vivo. The results were compared to determine which was the main
      factor influencing the stability of 9-nitrocamptothecin lactone form in rat
      plasma in vivo. RESULTS: The stability of lactone form in rat plasma was much
      higher in vivo than that in vitro. CONCLUSION: Blood cells help to increase the
      stability of 9-nitrocamptothecin lactone form. Clearance from blood in vivo is
      the primary factor which influences the plasma stability of 9-nitrocamptothecin
      lactone form. The kinetic process of 9-nitrocamptothecin lactone form and total
      drug in rats were both best fitted to a two-compartment model. However, the
      process of 9-nitrocamptothecin carboxylate form in vivo was best fitted to a one
      compartment model.

PMID- 16408804
TI  - [PEI-PMMA cationic nanoparticles as carriers for gene transfer].
AB  - AIM: To investigate the properties of cationic nanoparticles composed of poly
      (ethyleneimine)-g-poly (methyl methacrylate) (PEI-PMMA) as gene delivery carriers
      and explore the mechanism of PEI-PMMA nanoparticles mediated gene transfer.
      METHODS: PEI-PMMA nanoparticles were synthesized by free radical polymerization.
      The morphology of nanoparticles was observed by scanning electron microscopy. The
      particle size and zeta potential were measured by zeta sizer. The complex between
      pGL3 plasmid and nanoparticles was analyzed by gel electrophoresis; and PEI-PMMA
      nanoparticles mediated gene transfer into HeLa cells was observed by confocal
      laser scanning microscopy. RESULTS: PEI-PMMA nanoparticles are spherical shape
      and monodispersity. The particle size and zeta potential are 172 nm and +50.3 mV,
      respectively. When pGL3 plasmid complexed with nanoparticles at N/P ratio of 5: 1
      and 20: 1, the particle size of pGL3/nanoparticle complex are 133 and 139 nm and
      zeta potential is + 21.4 and + 33.7 mV, respectively. pGL3 plasmid complexed with
      nanoparticles completely at N/P ratio of 5: 1. PEI-PMMA nanoparticles can deliver
      pGL3 plasmid into HeLa cells by endocytosis and release pGL3 into the cytosol.
      CONCLUSION: PEI-PMMA nanoparticles effectively transferred DNA to target cells
      and it is a promising non-viral carrier for gene delivery.

PMID- 16408805
TI  - [Changes of gene expression profiles in CCl4 injured liver of mice].
AB  - AIM: To study the gene expression profiles between the CCl4 injured liver and
      normal liver in mice, and to screen the differentially expressed genes that
      relate to liver injury by CCl4 on a large scale using cDNA microarrays. METHODS:
      Male Kunming strain mice were divided into two groups: one was control group and
      another was CCl4 injured liver group that was given 0.1% CCI4 oil solution ip at
      dose of 10 mL x kg(-1) every three days, totally for ten times. Then mRNA in
      livers of the two groups of mice was extracted, separately, and reversely
      transcribed to cDNA with the incorporation of different fluorescent-labeled dUTP
      as the hybridization probes. The mixed probes were hybridized to the cDNA
      microarrays. The fluorescent signal values were acquired by scanner and analyzed
      with statistical software. RESULTS: Among the 14 100 target genes, 379 genes were
      differentially expressed, in which 163 genes were up-regulated and the other 216
      genes were down-regulated. They are closely related to a range of biological
      functions. CONCLUSION: Using the cDNA microarray and experimental animal modeling
      technique, the differentially expressed genes of CCl4 injured liver in mice on a
      large scale could be studied. It is useful for further investigation of the
      injury mechanism of CCl4.

PMID- 16408806
TI  - [Inhibitory effect of agarohexaose on antimycin A induced generation of reactive
      oxygen species].
AB  - AIM: To evaluate the hepatocyte protective effect of agarohexaose against
      indirect oxidative stress injury induced by antimycin A. METHODS: Antimycin A was
      used to induce oxidative injury of human hepatocyte L-02. The oxidative degree in
      cells was detected by dichlorofluorescin diacetate (DCFH-DA) and the fluorescence
      generation was recorded by flow cytometer and fluorescent microscope. The
      apoptosis of L-02 cells induced by oxidation was identified by TUNEL test, and
      the morphologic features of cells were also observed. RESULTS: Agarohexaose at
      concentration of 1 mg x mL(-1) inhibited the oxidation of DCFH into DCF
      significantly. The fluorescence intensity and oxidized cell number decreased
      after the incubation with agarohexaose. The photomicrographs of antimycin A and
      agarohexaose treated cells revealed that agarohexaose could reduce the apoptotic
      morphologic features. The TUNEL results also indicated that the number of
      apoptotic cells decreased significantly after the treatment of agarohexaose.
      CONCLUSION: Agarohexaose could inhibit the sudden increase reactive oxygen
      species (ROS) in cells significantly, and it also protected cells against
      oxidative stress injury in vitro.

PMID- 16408807
TI  - [Establishment of high-throughput drug screening model targeting retinoic acid
      receptor in cells].
AB  - AIM: To screen new drug for the treatment of acute promyelocytic leukemia,
      psoriasis and acne, high-throughput drug screening cell models marked by green
      fluorescent protein (GFP) have been established. METHODS: Eight repeats of
      retinoic acid response element (RARE) were synthesized and cloned into a GFP
      expression vector. This construct was stably transfected into cells in vitro.
      Stable and sensitive cell clones with high copy numbers of RARE were selected by
      retinoic acid (RA) using fluorescence-activated cell sorting (FACS). RESULTS: A
      cell line has been chosen to be high-throughput drug screening cell model. This
      model was shown with low background, high sensitive and good reproducibility, and
      was convenient and inexpensive. CONCLUSION: This drug screening cell model can be
      used for retinoic acid receptor target high-throughput drug screening.

PMID- 16408808
TI  - [Investigation on the hydroxylation metabolism of imrecoxib in vitro by using
      recombinant human CYPs].
AB  - AIM: To identify the drug-metabolizing enzymes involved in the hydroxylation of
      the new anti-inflammatory and anodyne imrecoxib. METHODS: Imrecoxib was incubated
      with heterologous expression human cytochrome P450 (rCYPs) in vitro, and
      metabolites and remained parent drug were detected with liquid chromatography
      multistage mass spectrometry. The contribution of 4 CYPs in the hydroxylation
      metabolism of imrecoxib was evaluated by total normalized rate (TNR) method.
      RESULTS: Imrecoxib is metabolized by CYP2C9, CYP2D6 and CYP3A4, with the rate of
      62.5%, 21.1% and 16.4%, respectively. CONCLUSION: CYP2C9 is the major enzyme
      involved in imrecoxib hydroxylation metabolism.

PMID- 16408809
TI  - [Effect of phenolic alkaloids of Menispermum dauricum on thrombosis and platelet
      aggregation].
AB  - AIM: To observe the effect of phenolic alkaloids of Menispermum dauricum (PAMD)
      on thrombosis and platelet aggregation, and to explore its mechanism of action.
      METHODS: Thrombosis was observed with arteriovenous shunt thrombus model in rat;
      platelet aggregation was determined by Born's method; ultrastructure of platelet
      was observed by transmission electron microscope; TXB2 or 6-keto-PGF1alpha levels
      were assessed by radioimmunoassay; and NO was determined by colorimetric method.
      RESULTS: PAMD dose-dependently inhibited experimental thrombus formation,
      platelet aggregation induced by ADP, AA and THR in vivo and ultrastructure
      changes stimulated by THR; PAMD increased the generation of 6-keto-PGF1alpha in
      thoracic aortae and NO level in plasma; and had no influence on TXB2 release (P >
      0.05). CONCLUSION: PAMD inhibited thrombosis and platelet aggregation, and its
      mechanism might be due to the increase of PGI2 and NO level.

PMID- 16408810
TI  - [Synthesis and antitumour activity of metal complexes of bacteriochlorophyll].
AB  - AIM: To find a new PDT sensitizer. METHODS: There were four complexes (Cu, Zn,
      Co, Ni) synthesized through reaction of metal and deprivating-Mg
      bacteriochlorophyll in the organic solvent. Their antitumor action was detected
      by MTT. RESULTS: The ultraviolet-visual spectrum and the fluorescence spectrum of
      these complexes showed that synthesis of these four complexes was succeeded. And
      these metal complexes have potent antitumor action on two kinds of leukaemic
      cells. CONCLUSION: Metal bacteriochlorophylls as PDT sensitizers have very good
      properties and this is a way to develop new PDT sensitizers.

PMID- 16408811
TI  - [Alkaline-degradation products of ginsenosides from leaves and stems of Panax
      quinquefolium].
AB  - AIM: To study the alkaline-degradation products of ginsenosides from leaves and
      stems of Panax quinquefolium L. METHODS: Isolation and purification were carried
      out on silica gel and HPLC; the structures of chemical constituents were
      elucidated by spectral analysis. RESULTS: From the alkaline-degradation products,
      nine compounds were identified as: 20 (S) -protopanaxadiol (I), 20 (S) -dammar-25
      (26)-ene-3beta, 12beta, 20-triol (II), 24 (R) -ocotillol (III), 20 (S) 
      protopanaxatriol (IV), 20 (S) -dammar-25 (26)-ene-3beta, 6alpha, 12beta, 20
      tetrol (V), dammar-20 (21), 24-diene-3beta, 12beta-diol (VI), dammar-20(21), 24
      diene-3beta, 6alpha, 12beta-triol (VII), 20 (S), 24 (S) -dammar-25 (26) -ene
      3beta, 6alpha, 12beta, 20, 24-pentanol (VIII), 20 (S) -dammar-23-ene-25
      hydroperoxyl-3beta, 6alpha, 12beta, 20-tetrol (IX). CONCLUSION: The configuration
      of C20 position of ginsenosides was not changed by alkaline-degradation. The
      complete assignments of 1H and 13C NMR chemical shifts of four new compounds V,
      VII, VIII, IX, were acquired by means of 2D NMR spectra. Compound I showed
      antitumor effect on human colon carcinoma cells in vitro.

PMID- 16408813
TI  - [Chemical constituents from the mangrove plant Ceriops tagal].
AB  - AIM: To investigate the secondary metabolites of the mangrove plant Ceriops
      tagal. METHODS: Column chromatography techniques including HPLC were used for the
      separation and purification, and extensive spectral analysis including various 2D
      NMR spectra were employed for structure elucidation. RESULTS: Nine compounds,
      namely, tagalsins A (1), ent-5alpha-dolabr-4 (18) -ene-15S,16-diol (2), squalene
      (3), betulinic acid (4), lup-20 (29) -en-3-on-28-oic acid (5), betulin (6), lup
      20 (29) -en-3-on-28-ol (7), beta-sitosterol (8), n-hexacosanylferulate (9) were
      obtained. Of which 1 and 2 belong to dolabrane diterpene. CONCLUSION: Compound 1
      is a new compound, and 2 to 9 are isolated from this species for the first time.

PMID- 16408812
TI  - [Alkaloids from the root of Lindera angustifolia].
AB  - AIM: To study the alkaloid constituents of the root of Lindera angustifolia
      Cheng. METHODS: The constituents were isolated and purified by column
      chromatography and the structures were characterized by spectral analysis.
      RESULTS: Seven aporphine alkaloids, laurotetanine (I), N-methyllaurotetanine
      (II), boldine (III), isoboldine (IV), norboldine (V), N
      ethoxycarbonyllaurotetanine (VII) and a quaternary isoquinoline alkaloid,
      magnocurarine (VI), were isolated and identified. The structure of VII was
      further identified by semi-synthesis with I as starting material. CONCLUSION: All
      compounds were obtained from this plant for the first time and compound VII was
      found as a naturally occurring compound for the first time.

PMID- 16408814
TI  - [Pharmacokinetics of (-)-clausenamide and its major metabolite 6-hydroxyl
      clausenamide in beagle dogs by HPLC/MS].
AB  - To establish a sensitive and accurate method to study the pharmacokinetics of (-)
      clausenamide [(-)-clau] and its major metabolite 6-hydroxyl-clausenamide (6-OH
      clau) in the plasma of the Beagle dog. METHODS: (-)-Clau was orally administered
      to six Beagle dogs at the dose of 30 mg x kg(-1), venous blood from front leg was
      sampled and plasma was separated for analysis. After extraction with ethyl
      acetate, the plasma samples were analyzed by HPLC/MS and the mobile phase was a
      mixture of methanol-water-acetic acid (60: 40: 0. 8) at the flow rate of 1.0 mL x
      min(-1). The API-ES positive ion SIM detection was carried out for the detection
      of both (-)-clau ([M + H] (+), m/z 298 ) and 6-OH-clau ([M + H - H2 O](+), m/z
      296) with glipzide (glip) ([M + H](+), m/z 446) as internal standard. The
      pharmacokinetic parameters were calculated by 3P97 software. RESULTS: There was
      good linear relationship ( r > 0. 999) between the SIM responses and the
      concentrations for (-)-clau and 6-OH-clau at the range from 1.0 to 200 ng x mL(
      1) and 0.2 to 40.0 ng x mL(-1), respectively. The absolute recovery was greater
      than 85%. The plasma concentration-time curves of (-)-clau and 6-OH-clau were
      both best fitted to a two-compartment model. The C(max) of (-)-clau and 6-OH-clau
      were (21 +/- 10) ng x mL(-1) and (3.9 +/- 2.2) ng x mL(-1), T(max) were (0.8 +/-
      0.5) h and (1.3 +/- 0.5) h, T 1/2 alpha were (0.9 +/- 0.6) hand (1.4 +/- 0.6) h,
      T 1/2 beta were (19 +/- 23) hand (13 +/- 12) h, AUC(0-24 h) were (69 +/- 14) h x
      ng x mL(-1) and (12 +/- 7) h x ng x mL(-1) respectively. CONCLUSION: The
      established HPLC/MS method was sensitive and specific for the determination of (
      )-clau. It was shown that the absorption and first phase elimination of (-)-clau
      were very quick in Beagle dogs, but the terminal elimination was very slow. The
      plasma concentration profile of its major metabolite 6-OH-clau was similar to (-)
      clau and the AUC was relatively small in comparison with (-)-clau.

PMID- 16408815
TI  - [Pharmacokinetics of fudosteine in healthy volunteers].
AB  - AIM: To study the pharmacokinetics of fudosteine in healthy volunteers after the
      single and multiple dose administration. METHODS: Thirty-six volunteers were
      divided into three groups randomly, each group included six men and six women. In
      the single dose design, the volunteers received either a single dose of 600 mg,
      400 mg or 200 mg fudosteine. After a one-week wash out period, the volunteers of
      400 mg group participated in the multiple dose design in which each volunteer
      received 400 mg fudosteine three times a day for five consecutive days. The
      plasma concentrations were determined by pre-column derivatization HPLC-FL method
      and the pharmacokinetic parameters of fudosteine were calculated. RESULTS: The
      obtained pharmacokinetic parameters of fudosteine in single dose of 600 mg, 400
      mg and 200 mg groups were as follows: T1/2 were (2.8 +/- 0.5), (2.7 +/- 0.5) and
      (3.2 +/- 0.6) h, respectively. T(max) were (0.51 +/- 0.22), (0.59 +/- 0.21) and
      (0.48 +/- 0.18) h, respectively. C(max) were (16 +/- 4), (11 +/- 3) and (6.1 +/-
      1.5) microg x mL(-1), respectively. The AUC(0-10 h) and C(max) correlated
      linearly with doses, respectively (r > 0.99). The T(max), C(max) and AUC values
      of fudosteine in healthy male volunteers were smaller than those in female
      volunteers, and the T1/2 value was longer than that in female volunteers. The
      obtained multi-dose pharmacokinetic parameters of fudosteine were as follows:
      C(ss) was (4.1 +/- 0.8) microg x mL(-1); DF was 3.0 +/- 0.7; T1/2 was (2.5 +/-
      0.4) h; T(max) was (0.6 +/- 0.3) h; C(max) was (13.2 +/- 1.3) microg x mL(-1).
      CONCLUSION: The values of pharmacokinetic parameters in healthy volunteers were
      linear in the range from 200 mg to 600 mg. Statistic analysis results showed that
      the differences of AUC and C(max) between men and women were not resulted from
      sexual differences, but from the weight differences. There was no significant
      difference in pharmacokinetic parameters between single dose and multi-dose.

PMID- 16408816
TI  - [Cellular uptake behavior of antisense oligodeoxynucleotides polymethacrylate
      submicroparticles].
AB  - AIM: To survey the uptake behavior and subcellular distribution of antisense
      oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) and infer
      its mechanism in MGC cell lines. METHODS: MGC cells were incubated at certain
      concentration of AS-ODN-SMP or AS-ODN for 8 h at 4 degrees C or 37 degrees C.
      Then the fluorescence oligodeoxynucleotide- labeled cells were counted by flow
      cytometer and the intracellular fluorescence intensity was determined after
      incubated with chloroquine for 2 h. RESULTS: Cellular uptake of
      oligodeoxynucleotides was significantly increased following application of AS-ODN
      SMP and total intracellular fluorescence intensity was enhanced by 683 folds with
      the vehicle concentration of 20 microg x mL(-1). AS-ODN-SMP entranced to cells
      profoundly with temperature-dependent manner. Rare cells took on fluorescence
      when incubated at 4 degrees C, while 37 degrees C they were significantly
      increased. But the intracellular fluorescence intensity appeared same level in
      present or absent of chloroquine. CONCLUSION: With the help of polyacrylate
      submicroparticles, oligonucleotides efficiently entranced the cells via
      endocytosis and could successfully escape the degradation in lysosome.

PMID- 16408817
TI  - [Effects of iptakalim on intracellular calcium concentrations, PKA and PKC
      activities in rat tail artery smooth muscle cells].
AB  - AIM: To investigate the effects of iptakalim, a new structural potassium channel
      opener (KCO), on intracellular calcium concentration ([Ca2+]i), protein kinase C
      (PKC), and cAMP-dependent kinase (PKA) activities in rat tail artery smooth
      muscle cells (RTA-SMC), and to analyze mechanisms involved in iptakalim reversing
      hypertensive vascular remodeling. METHODS: RTA-SMC was cultured and passages 3-4
      were used for experiment. [Ca2+] i was measured by laser scanning confocal
      microscope after loaded with fluorescent indicator fluo-3-acetoxymethylester, and
      activities of PKA and PKC were detected by commercial assay kits (the
      nonradioactive PepTag system) following instructions. RESULTS: Compared with
      baseline, [Ca2+] i reduced significantly after iptakalim- or pinacidil-treatment
      at concentrations of 0.1, 1 and 10 micromol x L(-1), while diazoxide caused
      significant decrease at concentration of 1 and 10 micromol x L(-1). After
      preincubation with 1 micromol x L(-1) glibenclamide, [Ca2+] i was not
      significantly changed when iptakalim, pinacidil or diazoxide were added at
      concentration of 0.1 and 1 micromol x L(-1). Activities of PKA and PKC increased
      significantly by 1 micromol x L(-1) iptakalim- or pinacidil-treatment, while 1
      micromol x L(-1) diazoxide induced significant change in activity of PKC but not
      in that of PKA. CONCLUSION: The characteristics of iptakalim on [Ca2+] i, PKA and
      PKC are more or less similar to those of pinacidil. Iptakalim decreased [Ca2+] i
      while increased PKA and PKC activities of RTA-SMCs, which may contribute to its
      ability to reverse antihypertensive vascular remodeling.

PMID- 16408818
TI  - Determination of the nateglinide polymorphism structure and the drug effect.

PMID- 16408819
TI  - [Calcium phosphate cements in medicine and dentistry--a review of literature].
AB  - Calcium phosphates represent the largest group of biominerals in vertebrate
      animals. They also have many uses in industry, agriculture, medicine and everyday
      life. The calcium phosphates containing the ionic species HPO4(2-) and PO4(3-)
      are biologically relevant. In medicine, calcium phosphates have been used for
      bone regeneration for several decades. The requirement of a mouldable, self
      setting material has been fulfilled since the mid-1980s because of the
      development of calcium phosphate cements. Basically, they consist of a powder (e.
      g. di-, tri- or tetra-calcium phosphates) that is mixed with a liquid. Their
      properties depend on kind, amount, and location of each atom within the crystal
      structure. In dentistry calcium phosphate cements play a secondary role at the
      moment, although they often have an excellent biocompatibility. This review gives
      a general idea on development and chemistry of calcium phosphate cements and
      presents different cement types tested in vitro and in vivo.

PMID- 16408820
TI  - [Eating disorders (I)--medical and psychiatric aspects].
AB  - Adolescent, predominantly female patients suffering from eating disorders usually
      reveal characteristic personality traits which should be taken into account
      during the treatment of such cases. Some patients deny their illness, others
      again feel ashamed of it. At any rate, we ought to respect the patients'
      integrity and their sense of self-worth. Such disorders tend to result from the
      stress of being unable to cope with the multiple demands made by the biological
      and social changes of the patients' development into full maturity. Additional
      predisposing factors should be noted. Eating disorders are often accompanied by
      specific psychic and somatic symptoms in terms of comorbidity. These symptoms
      have to be anamnestically accounted for since they may later result in oral
      symptoms. A considerable number of these patients suffering from eating disorders
      either do not completely recover or else tend to relapse.

PMID- 16408821
TI  - [Eating disorders (II)--dental aspects].
AB  - Patients suffering from eating disorders exhibit oral symptoms indicative to the
      otherwise concealed illness. The most striking features are the intrinsic
      erosions due to the regular surreptitious vomiting. They occur in very typical
      locations within the dental arches and have been termed "perimolysis". Dental
      professionals are often the first to discover and diagnose eating disorders by
      detecting perimolysis and consequently face the difficult task to motivate the
      patients--who often deny their illness--to seek psychiatric help and dental care.
      Such motivation must be done while respecting the patients' integrity and sense
      of self-worth. The primary goal of dental care is to preserve the remaining teeth
      and to prevent further erosive loss of dental hard tissue. The key elements of a
      dental preventive programme based on pathophysiologic grounds are to enhance
      local defence mechanisms, to offer chemical and mechanical protection and to
      diminish abrasive and erosive challenges. Dental restorative therapy must be part
      of a combined medical and dental treatment plan and should not be started before
      the eating disorder has been treated and the patients are considered to have
      stable prognosis. In view of the young age of the patients, the large extension
      of the erosive lesions and in order to avoid endodontological treatment of mostly
      sound pulps, non-invasive restorative concepts using adhesive technology should
      be preferably used. Prophylactic measures and restorative treatment are covered
      by health insurance (KGV; KLV 18c, 7) if the patients undergo psychiatric or
      similar adequate treatment.

PMID- 16408823
TI  - [Composite curing with new LED equipment].
AB  - Standardized holes ("cavities") measuring 4 mm in diameter and 8 mm in depth were
      prepared using plexiglass cubes. The following LCUs were tested: Astralis 10
      Halogen light curing units (LCU), Bluephase, Elipar Freelight 2 and SmartLite LED
      LCUs. Each LCU was examined according to the following test conditions. Light
      exposure time of 20 s and 40 s. Polymerization directly onto the composite, with
      a distance of 4 mm or through a 3 mm thick ceramic disk, respectively. The
      composite Tetric Ceram (A3) was inserted in one batch and after a seven-day
      incubation period the cubes were sectioned into two halves and polished. Knoop
      microhardness was determined 100, 200, 500, 1000, 1500, 2500, 3000, 4000, 5000
      and 6000 microm from the occlusal surface. The total degree of polymerization of
      a composite specimen for any given curing time and curing light was determined by
      calculating the area under the hardness curve. Multiple linear regression
      revealed that the distance of the light tip from the composite, curing time and
      the LCU had a significant association with the degree of polymerization (p <
      0.001). The same pattern of cure profile was shown by all LCUs during the course
      of the test. The hardest composite was usually encountered around 200 microm from
      the occlusal surface. It was concluded that without irradiation through ceramic
      and a light tip close to the composite a light exposure time of 20 s will
      sufficiently polymerize an increment of at least 2 mm. Polymerization through
      ceramic needs a curing time of 40 s from each side.

PMID- 16408822
TI  - [Treatment of crown fractured incisors: reattachment instead of restoration?].
AB  - Crown fractures are the most common form of traumatic dental injuries in the
      permanent dentition. Reattachment of the coronal fragment to the remaining tooth
      structure may offer a conservative, esthetic and cost-effective restorative
      option which has been shown to be an accepted alternative to conventional
      restoration (resin composite build-up, veneer or crown) of the fractured teeth.
      Fragment retention is significantly influenced by reattachment techniques and
      materials. Regarding reattachment techniques, placement of an internal groove
      seems advisable when the remnant and the fragment fit well, while an
      overcontouration should be used when the partial loss of hard tissue must be
      compensated. Materials used for reattachment seem to be less important than
      technique for a successful treatment, but adhesives and composite resin materials
      should correspond to each other. However, up to now, self-etching adhesives have
      shown less fracture strength of the reattachment than multi-bottle adhesives.
      Since many case reports and several clinical studies reported clinical success,
      further studies are recommended to analyse the impact of reattachment techniques
      and materials on the long-term survival of fragment bonding.

PMID- 16408824
TI  - [The Retroplast Technique. Retrograde obturation with composite and adhesive
      technique in endodontic surgery].
AB  - Endodontic surgery, and in particular periapical surgery, has seen a significant
      development in the last few years, mainly following the introduction of
      microsurgical principles and the use of magnification devices. The successful
      outcome of periapical surgery, however, is based on the quality of the root-end
      obturation that should prevent any reinfection originating from the root canal.
      Since amalgam as a root-end sealing material was abandoned many years ago, a
      great diversity of obturation techniques and materials have been described.
      Besides the standard root-end cavity preparation with microtips, the author today
      has a preference for the Retroplast-technique. The paper describes this technique
      in detail and reports the possibilities and limits of this obturation method.

PMID- 16408825
TI  - [Dealing with adverse drug reactions in dentistry. Procedures on encountering
      adverse drug reactions and goal of the Swiss Pharmacovigilance system].
AB  - Dentists may be confronted with adverse drug reactions (ADRs) in their dental
      practice, and are--like other health professionals--obliged to report certain
      ADRs. The aim of this article is to sensitise dentists for this topic, to show
      how to proceed in case of a supposed ADR, and to emphasise the importance of
      spontaneous reporting of ADRs. ADRs may not always be clearly distinguished from
      symptoms of underlying diseases, and in cases of polypharmacy multiple drugs may
      be responsible for the reaction. It is therefore important to get a detailed
      medical history, and to establish a temporal relationship between start of a
      therapy and appearance of the symptom. Information from the medical literature,
      exclusion of other possible causes, and identification of risk factors help to
      confirm a causal relationship between a suspected drug and an observed reaction.
      In Switzerland severe and unexpected ADRs have to be reported to one of the
      regional Pharmacovigilance centres with the yellow ADR reporting form from
      Swissmedic. The spontaneous reports of ADRs help to early identify new problems
      of a drug therapy, and permit to take measures to minimise the risk.

PMID- 16408827
TI  - [Loss and uncontrolled use of radioactive sources].
AB  - In the course of history, exposure to radioactive sources escaping regular
      control, has been the main cause of fatal accidents, with the exception of the
      reactor accident at Chernobyl. After the disintegration of the Soviet Union,
      numerous lost sources have been found, sometimes with serious physical damage.
      The attacks of September 11, 2001 have focussed the attention on the possibility
      of nuclear terrorism. Although the risks of fatal consequences are rather
      limited, the possible uncontrolled exposure to ionizing radiation has an
      important psycho-social impact on the population. After a brief survey of the
      types of radioactive sources for medical and industrial applications and a
      discussion of the risks and exposure routes, possible scenarios are illustrated
      by well documented case histories. The main conclusions of this analysis are:
      Radioactive materials are not unique as a potential threat by toxic materials.
      The most serious consequences for individuals occur as the result of external
      radiation, mostly with skin contact with medium-active sources which are
      relatively easily accessible. The collective impact is mostly psycho-social and
      is more important for a dispersed contamination of the environment. Many sources
      are detected via medical complaints. The knowledge of the specific symptoms is
      consequently very important. A dispersion of radioactive contamination has
      usually considerable economic consequences. Accidents occur particularly, but
      certainly not exclusively, in relatively unstable countries. Change of owner or
      final evacuation of the source constitute a critical phase in many scenarios.

PMID- 16408826
TI  - Clinical pharmacology of non opioid analgesics in neonates.
AB  - An integrated approach of neonatal analgesia starts with the systematic
      evaluation of pain and should be followed by effective interventions, mainly
      based on the appropriate (i.e. safe and effective) administration of analgesics.
      In contrast to the more potent opioids, data on the pharmacokinetics and 
      dynamics of non-opioid analgesics in this specific population are still rare or
      even lacking. We therefore evaluated various aspects of developmental
      pharmacology of non-opioid analgesics (paracetamol, ibuprofen, acetylsalicyl
      acid) in neonates. We first performed a single dose propacetamol study in preterm
      and term neonates. Based on these preliminary findings, a repeated dose
      administration scheme was developed and tested and maturational aspects from
      preterm till teenage were documented. Although non-selective COX-inhibitors might
      be effective in the treatment of postoperative or inflammatory pain syndromes in
      neonates, potential efficacy should be balanced against the drugs' safety
      profile. Neonatal renal clearance strongly depends on glomerular filtration rate
      (GFR) and GFR itself strongly depends on the vaso-dilatative of prostaglandins on
      the afferent arterioli. We therefore evaluated the impact of the administration
      of ibuprofen or acetylsalicylic acid on renal clearance in preterm infants and
      hereby used amikacin clearance as a surrogate marker. We hereby documented the
      negative effect of ibuprofen on glomerular filtration rate in preterm infants up
      to 34 weeks and we were able to show that ibuprofen and acetylsalicylic acid had
      an equal impact on the glomerular filtration rate.

PMID- 16408828
TI  - [Standpoint of the Federal Agency for Nuclear Control].
AB  - This paper presents how radioactive material is managed in Belgium according to
      international standards, European and Belgian legislation. The positions of the
      Belgian safety authority are presented including on the question of loss of
      control of those radioactive material.

PMID- 16408829
TI  - [Organization of the nuclear emergency plan].
AB  - The first Belgian nuclear emergency plan was drawn up in the aftermath of the
      Chernobyl accident and was primarily aimed at dealing with the consequences of
      major accidents happening in large nuclear facilities like nuclear power plants.
      Both the experience during a decade of nuclear emergency exercises and a changing
      environment with increased menace of malevolent actions by terrorists urged the
      modification and extension of the initial plan; The latest "Nuclear and
      radiological emergency plan for the Belgian territory" was published as the Royal
      Decree of October 17th, 2003. In contrast to what happened in other emergency
      situations, nuclear and radiological emergencies are, from the moment they are
      recognised as such and regardless of their (potential) impact, coordinated at the
      level of the federal authorities. They will gather at the Coordination and Crisis
      Centre in Brussels. Political decision making will be based both on radiological
      and socio-economical considerations. The radiological evaluation will take into
      account on-site observations such as the state and evolution of some crucial
      technical parameters, meteorological data (observations and forecast) and
      measured radiological data, where available. Protective measures may be proposed
      by the radiological experts, but will probably be modified in the light of socio
      economical considerations such as the social and/or economical disruption that
      might arise from fully deploying these proposed measures. The final decision will
      be taken by political authorities, more particularly the Minister of the
      Interior. The execution of the decided protective measures will be the
      responsibility of one or more provinces, who can further delegate to the
      municipal level and/or to particular services such as the police force, fire
      department, civil protection, health services and communication experts. The
      nuclear and radiological emergency plan also deals with some common protective
      measures such as the installation of a dissuasion perimeter or exclusion zone,
      the evacuation, sheltering, protection of the food chain, the use of stable
      iodine and the decontamination from radioactive substances. At least some of the
      countermeasures ask for -often extensive- preparation in advance, which is
      generally done in adefined geographical area in the vicinity of a nuclear
      facility, referred to as "emergency planning zone" for that particular
      countermeasure and facility. However, the existence of these zones does in no way
      exclude the application of this countermeasure outside of them. The radiological
      evaluation is being prepared by introducing "emergency reference levels", for
      which the Federal Agency for Nuclear Control is responsible. This consists in pre
      defining radiation doses which "generally" to "almost invariably" call for the
      adoption of a given countermeasure. Finally, the nuclear and radiological
      emergency plan includes stipulations on the required information to the
      population, on the education and training of (potentially) intervening parties as
      well as on the minimum requirements for running nuclear emergency exercises.

PMID- 16408830
TI  - [Details in relation to emergency planning in case of undesired dispersion of
      radioactivity].
AB  - In the present context of terrorist threat and the multiple uses of radioactive
      sources for many applications, one cannot exclude the probability of a
      contamination with radioactive products in the public domain. The most probable
      scenario is the loss or theft of a source, or a source showing up in some
      unexpected location (orphan sources). Terrorist actions may lead to a similar
      problem (radiological dispersion devices, RDD). If the radiological situation is
      serious, the Belgian emergency plan will be declared, aiming at protecting the
      population as adequately as possible. However, the emergency plan has mainly been
      conceived for an accident in a nuclear facility; as exercises are organised
      frequently and as the technical possibilities can be studied in advance, the
      experts are better prepared for such accidents. But a radioactive contamination
      in some other location would lead to modifications to be made, which may result
      in less effective response. Indeed, the very first stage--an alert--will
      presumably be missing. Or the contamination may occur in a town not involved in
      radiological emergency exercises, leading to a local lack of means. The main
      concern is that this should not lead to a degradation of the response. It is
      essential that all decision makers at all levels know how to deal with the
      situation, or at least know whom to call for support (Mayors, emergency workers)
      A special focus on medical staff who could be involved with potentially strong
      (yet local) fields of radiation, injured people with contamination, but also (and
      presumably especially) with the psychological impact of large groups of
      population feeling concerned about the potential health or societal (and
      economic) consequences for themselves or their children. Whether the probability
      of such an event is large in Belgium or not is in that sense less relevant: the
      probability surely isn't zero, and as such an adapted preparation scheme is
      absolutely necessary.

PMID- 16408831
TI  - [Medical interventions: external and internal decontamination of people].
AB  - In most cases, external contamination of persons can be monitored easily.
      Nevertheless, proper measurement techniques must be used. For that reason,
      contamination measurements must be carried out by health physics professionals.
      In all efforts to decontaminate intact skin, care must be taken to prevent skin
      damage. Internal contamination can pose much more problems. Here, decontamination
      is based on dilution and/or complexation therapy, thus reducing the uptake in
      critical organs and tissues. Also by stimulating the excretion of radionuclides,
      internal doses can be reduced significantly. Treatment of contaminated wounds
      always is a priority because of the internal contamination risk. Radioactive
      waste has to be collected on an individual basis (for dosimetry purposes).
      Distance must be kept between radioactive waste and monitoring instruments. Every
      effort should be made to prevent the spread of contamination; only urgent life
      saving actions may be an exception. There certainly will be a need for counseling
      those suffering from the psychological impact of (even minor) contamination
      accidents. From a public health perspective, the long term psychosocial effects
      of nuclear catastrophes may eventually be more prevalent than their physical
      health consequences. Each (general) practitioner should be vigilant to suspicious
      clinical signs that may be radiation related. However, high threshold doses to
      critical organs (bone marrow, skin, small intestine) must be crossed before
      clinical signs arise. In Belgium, several most interesting texts regarding
      radiation problems have already been distributed to medical and paramedical
      professionals, partly by the authorities.

PMID- 16408832
TI  - Differential glutamatergic modulation of monoamine release in the limbic lobe by
      selective anticonvulsant ionotropic and metabotropic glutamate receptor ligands.
AB  - Several researchers are currently trying to unravel neurobiological relationships
      between epilepsy and depression. After all, these disorders often develop in the
      same vulnerable brain regions and the importance of comorbid depression and
      epilepsy is still underscored. Facilitation of central serotonin (5-HT), dopamine
      (DA) and noradrenaline (NAD) release seems to be associated with both
      anticonvulsant and antidepressant effects. We show that selective ionotropic and
      metabotropic glutamate receptor ligands with anticonvulsant properties
      differentially modulate NAD, DA and 5-HT in rat limbic lobe structures.

PMID- 16408833
TI  - Comparison of two birnavirus-rhabdovirus coinfections in fish cell lines.
AB  - Aquabirnaviruses, such as the infectious pancreatic necrosis virus (IPNV),
      Novirhabdoviruses, such as the infectious hematopoiteic necrosis virus (IHNV) and
      the viral hemorrhagic septicemia virus (VHSV), cause considerable losses to the
      salmonid industry worldwide. Coinfections of 2 viruses have been described, but
      the interactions between rhabdoviruses and birnaviruses have not been examined
      closely. Using virus titration, flow cytometry and RT-PCR assays, we compared the
      effect of IPNV on the replication of IHNV and VHSV in tissue culture cells. RT
      PCR assays indicated that simultaneous infection of IPNV with VHSV does not
      affect the replication of the rhabdovirus either in the first or successive
      passages; the infective titers were similar in single and double infections. In
      contrast, coinfection of IPNV with IHNV induced a fall in infectivity, with
      reduced expression of IHNV viral antigens in BF-2 cells from Lepomis macrochirus
      and a loss of 4.5 log10 units of the infective titer after 3 successive passages.
      It was possible to stimulate BF-2 cells to produce significant interferon-like
      activity against IHNV but not against VHSV.

PMID- 16408834
TI  - Different responses to infectious hypodermal and hematopoietic necrosis virus
      (IHHNV) in Penaeus monodon and P. vannamei.
AB  - Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is widespread in
      cultured Penaeus monodon and P. vannamei in Thailand. It causes runt-deformity
      syndrome that is characterized by physical abnormalities and stunted growth in P.
      vannamei, but causes no apparent disease in P. monodon. In both species, the
      virus may produce Cowdry Type A inclusions in tissues of ectodermal and
      mesodermal origin, but these are common in P. vannamei and rare in P. monodon.
      The virus can be more easily detected in both species by IHHNV-specific PCR
      primers. By in situ hybridization (ISH) using specific IHHNV probes, fixed
      phagocytes associated with myocardial cells tended to show strong positive
      reactions in both shrimp species. Ovarian and neural tissue (neurons in the nerve
      ganglia and glial cells in the nerve cord) were ISH positive for IHHNV only in P.
      vannamei. By transmission electron microscopy, necrotic cells were found in the
      gills of IHHNV-infected P. vannamei, while paracrystalline arrays of virions and
      apoptotic cells rather than necrotic cells were found in the lymphoid organ of
      IHHNV-infected P. monodon. Thus, it is possible that apoptosis in P. monodon
      contributes to the absence of clinical disease from IHHNV. These findings reveal
      different responses to IHHNV infection by the 2 shrimp species. A curious feature
      of IHHNV infection in P. monodon was inconsistency in the comparative viral load
      amongst tissues of different specimens, as detected by both ISH and real-time
      PCR. This inconsistency in apparent tissue preference and the reasons for
      different cellular responses between the 2 shrimp species remain unexplained.

PMID- 16408835
TI  - Pathogenicity of Vibrio penaeicida for white shrimp Litopenaeus vannamei: a
      cysteine protease-like exotoxin as a virulence factor.
AB  - The pathogenicity of Vibrio penaeicida Strains KH-1 and AM101, their culture-free
      supernatant (CFS), and their protein fraction obtained by 40% of ammonium sulfate
      precipitation (PFs40) were assessed in experimental challenges against juvenile
      Litopenaeus vannamei. Live Vibrio cells, CFS, and PFs40 from the AM101 strain
      produced a significantly higher mortality (p < 0.05) compared to the KH-1 strain.
      Toxicity and median lethal doses (LD50) of Fast Protein Liquid Chromatography
      (FPLC) products were evaluated on L. vannamei. The first FPLC fraction sample (A)
      from PFs40 of the AM101 strain displayed LD50 values of 1.68 and 5.61 microg
      protein ind.(-1), respectively. The second FPLC process from Fraction A showed a
      peak (A1) also with toxic effects to shrimp. PFs40, Fraction A, and Peak A1
      showed a 38.5 kDa molecular band (SDS-PAGE), with activity on a gelatin protease
      zymogram. The lethal effect of PFs40 and Fraction A was inhibited by Proteinase
      K, CuCl2, E-64, and heat (60 and 100 degrees C) treatments, but was not inhibited
      by EDTA-Na2, aprotinin, and soy trypsin treatments. These results and the
      zymogram inhibition test suggest the presence of a cysteine protease-like
      proteinaceous exotoxin as a dominant protease, secreted by V. penaeicida Strain
      AM101.

PMID- 16408836
TI  - Pathogenic bacteria isolated from disease outbreaks in shellfish hatcheries.
      First description of Vibrio neptunius as an oyster pathogen.
AB  - Shellfish hatcheries are often affected by disease outbreaks. Three such episodes
      were investigated in different Galician hatcheries in order to establish the
      relationship between present microbiota and mortalities. Isolates were obtained
      from various parts of the hatcheries. Experimental tests for pathogenicity were
      carried out in microscale experiments using selected strains on Ostrea edulis
      larvae. The pathogenicity of 1 strain from each outbreak was demonstrated and
      shown to cause high mortalities (ranging from 98.5 to 100%) in 72 to 96 h after
      inoculation of larval cultures. All 3 strains belong to the genus Vibrio. One of
      the strains was identified as Vibrio neptunius and is the first description of
      this species as a molluscan pathogen. The other 2 strains showed low similarity
      with the Vibrio species analysed and may constitute new species within this
      genus.

PMID- 16408837
TI  - Effects of triclosan on growth, viability and fatty acid synthesis of the oyster
      protozoan parasite Perkinsus marinus.
AB  - Perkinsus marinus, a protozoan parasite of the Eastern oyster Crassostrea
      virginica, has severely impacted oyster populations from the Mid-Atlantic region
      to the Gulf of Mexico coast of North America for more than 30 yr. Although a
      chemotherapeutic treatment to reduce or eliminate P. marinus from infected
      oysters would be useful for research and hatchery operations, an effective and
      practical drug treatment does not currently exist. In this study, the
      antimicrobial drug triclosan 5-chloro-2-(2,4 dichlorophenoxy) phenol, a specific
      inhibitor of Fab1 (enoyl-acyl-carrier-protein reductase), an enzyme in the Type
      II class of fatty acid synthetases, was tested for its effects on viability,
      proliferation and fatty acid synthesis of in vitro-cultured P. marinus meronts.
      Treatment of P. marinus meront cell cultures with concentrations of > or = 2
      microM triclosan at 28 degrees C (a temperature favorable for parasite
      proliferation) for up to 6 d stopped proliferation of the parasite. Treatment at
      > or = 5 microM at 28 degrees C greatly reduced the viability and fatty acid
      synthesis of meront cells. Oyster hemocytes treated with > or = 20 microM
      triclosan exhibited no significant (p < 0.05) reduction in viability relative to
      controls for up to 24 h at 13 degrees C. P. marinus meronts exposed to > or = 2
      microM triclosan for 24 h at 13 degrees C exhibited significantly (p < 0.05)
      lower viability relative to controls. Exposure of P. marinus meronts to triclosan
      concentrations of > or = 20 microM resulted in > 50% mortality of P. marinus
      cells after 24 h. These results suggest that triclosan may be effective in
      treating P. marinus-infected oysters.

PMID- 16408838
TI  - Identification and partial characterisation of metalloproteases secreted by a
      Mesanophrys-like ciliate parasite of the Norway lobster Nephrops norvegicus.
AB  - A ciliate parasite, tentatively identified as Mesanophrys sp. of Norway lobsters
      Nephrops norvegicus, is demonstrated to secrete several proteases into the
      culture medium (modified Nephrops saline). Analyses using substrate-impregnated
      sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed 12
      activity bands differing greatly in mobility in the gels. The complete inhibition
      of proteolytic activity by 1,10-phenanthroline indicated that the proteases are
      of the metallo class. The proteases were active at the physiological temperature
      (8 degrees C) and haemolymph pH (7.8) of the host. The proteases were selective
      in the degradation of several host proteins, including the myosin heavy chain,
      which is a major structural component of lobster muscle. Consequently, these
      proteases may have important roles in several aspects of the host-parasite
      interaction including invasion, nutrient uptake by the ciliate, and pathogenesis.

PMID- 16408839
TI  - Differences in metabolic response to Loma salmonae infection in juvenile rainbow
      trout Oncorhynchus mykiss and brook trout Salvelinus fontinalis.
AB  - Routine and post-exercise metabolic rates were measured for juvenile rainbow
      trout Oncorhynchus mykiss and brook trout Salvelinus fontinalis infected with the
      microsporidium gill parasite Loma salmonae under laboratory conditions. Rainbow
      trout increased routine and post-exercise metabolic rate in response to infection
      compared with controls. Brook trout, on the other hand, lowered routine metabolic
      rate without effecting post-exercise metabolic rate compared to controls. The
      result of these 2 different strategies may either reflect defense of metabolic
      scope or a difference in the rate of recovery of the excess post-exercise oxygen
      consumption between the 2 species in response to the same infection.

PMID- 16408841
TI  - Scleractinian coral diseases in south Florida: incidence, species susceptibility,
      and mortality.
AB  - There are limited quantitative data available documenting the natural, or non
      epizootic, occurrence of scleractinian coral diseases over multiple years.
      Individual coral colonies exhibiting black band disease (BBD), white plague (WP),
      dark spots syndrome (DSS), and white band disease (WBD) were monitored 3 times
      per year on 5 south Florida reefs over a 2 yr period. Surveys included
      measurements of coral population composition, coral diversity, disease type,
      coral species affected, colony size, percent of colony affected, and the number
      of lesions or active infections per colony. Data on re-infections of the same
      colonies, multiple infections per colony, disease duration, disease-associated
      tissue mortality, and coral recruitment are also presented. A total of 674 coral
      colonies exhibiting coral diseases were tagged and monitored. DSS was the most
      common syndrome (n = 620 infected colonies), but BBD and WP infections caused the
      largest amount of coral tissue death. The only disease that exhibited a linear
      increase in incidence with elevated temperature was BBD. DSS and BBD were the
      most persistent conditions, and WP infections were comparatively short-lived,
      with obvious signs of disease typically disappearing after 2 to 3 mo. The only
      disease that caused total colony death as oppposed to partial mortality during
      the survey period was WBD. WP and DSS incidence was significantly positively
      correlated with the relative frequency of the species most commonly affected by
      each disease at each study site. Of the 61 colonies examined in the recruitment
      survey, only 5 scleractinian coral recruits were identified. The most commonly
      recorded colonizer of exposed coral skeleton was filamentous/turf algae, thus
      indicating the potential for a shift towards algal-dominated reef communities.

PMID- 16408840
TI  - Changes in epizoic crustacean infestations during cetacean die-offs: the mass
      mortality of Mediterranean striped dolphins Stenella coeruleoalba revisited.
AB  - In the summer and autumn of 1990, a cetacean morbillivirus caused a massive
      epizootic mortality of striped dolphins Stenella coeruleoalba in the western
      Mediterranean. Previous circumstantial evidence suggested that the disease could
      also have increased host susceptibility to infestations with epizoic crustaceans.
      In this study we provide strong evidence supporting this hypothesis. We examined
      striped dolphins stranded along the Mediterranean central coast of Spain from
      1981 to 2004 (n = 136), and recorded data on prevalence, intensity of
      infestation, size and reproductive status of 2 sessile crustacean species
      specific to cetaceans, the phoront cirriped Xenobalanus globicipitis and the
      mesoparasitic copepod Pennella balaenopterae. Compared with the pre-epizootic (n
      = 12) and post-epizootic (n = 62) dolphin samples, the following changes were
      noted in the dolphins stranded during the epizootic (n = 62): (1) the prevalence
      of both X. globicipitis and P. balaenopterae increased; (2) the intensity of X.
      globicipitis and P. balaenopterae infestations did not increase; indeed, it was
      even slightly lower than in the other periods, as was their degree of
      aggregation; (3) individuals of both species were smaller, and a higher
      proportion were non-gravid; (4) the 2 species tended to co-occur in the same
      dolphins, but their numbers did not co-vary. These patterns strongly suggest
      that, during the epizootic, there was a short-term increase in the probability of
      infestation of these 2 species because of the sudden rise in the population of
      susceptible hosts; the growth of the new recruits was limited by the early death
      of dolphins. The high susceptibility was likely related to the immunosuppressive
      effects of viral infection and the abnormally heavy loads of polychlorinated
      biphenyls found in sick dolphins; the level of inbreeding was also higher in
      dolphins from the 'epizootic' sample. Epizoic crustaceans could be suitable
      indicators of health in cetacean populations.

PMID- 16408843
TI  - Construction of a virulent, green fluorescent protein-tagged Yersinia ruckeri and
      detection in trout tissues after intraperitoneal and immersion challenge.
AB  - A green fluorescent protein (GFP) expressing strain of Yersinia ruckeri was
      created by the transposition of a Tn10-GFP-kan cassette into the genome of Y.
      ruckeri Strain YRNC10. The derivative, YRNC10-gfp, was highly GFP fluorescent,
      retained the gfp-km marker in the absence of kanamycin selection, and exhibited
      in vitro growth kinetics similar to those of the wild type strain. YRNC10-gfp
      colonized and caused mortality in immersion and intraperitoneally challenged
      rainbow trout Oncorhynchus mykiss, although it was modestly attenuated compared
      to the wild type strain. The distribution and location of YRNC10-gfp in infected
      fish was visualized by epifluorescence microscopy. Abundant extracellular
      bacteria and a small number of intracellular bacteria were observed in the
      kidney, spleen and peripheral blood. To determine the percentage of trout cells
      containing intracellular bacteria, GFP fluorescence was measured by flow
      cytometry. A small population of GFP positive leukocytes was detected in
      peripheral blood (1.6%), spleen (1.1%) and anterior kidney (0.4%) tissues. In
      summary, this is the first report of the construction of a virulent, GFP-tagged
      Y. ruckeri, which may be a useful model for detecting and imaging the
      interactions between an aquatic pathogen and the natural salmonid host.

PMID- 16408842
TI  - Molecular cloning of the gyrA gene and characterization of its mutation in
      clinical isolates of quinolone-resistant Edwardsiella tarda.
AB  - Knowing the entire sequence of the gene encoding the DNA gyrase Subunit A (gyrA)
      of Edwardsiella tarda could be very useful for confirming the role of gyrA in
      quinolone resistance. Degenerate primers for the amplification of gyrA were
      designed from consensus nucleotide sequences of gyrA from 9 different Gram
      negative bacteria, including Escherichia coli. With these primers, DNA segments
      of the predicted size were amplified from the genomic DNA of E. tarda and then
      the flanking sequences were determined by cassette ligation-mediated polymerase
      chain reaction. The nucleotide sequence of gyrA was highly homologous to those of
      other bacterial species, in both the whole open-reading frame and the quinolone
      resistance-determining region (QRDR). The 2637-bp gyrA gene encodes a protein of
      878 amino acids, preceded by a putative promoter, ribosome binding site and
      inverted repeated sequences for cruciform structures of DNA. However, the
      nucleotide sequence of the flanking region did not show any homologies with those
      of other bacterial DNA gyrase Subunit B genes (gyrB) and suggested the gyrase
      genes, gyrA and gyrB, are non-continuous on the chromosome of E. tarda. All of
      the 12 quinolone-resistant isolates examined have an alteration within the QRDR,
      Ser83 --> Arg, suggesting that, in E. tarda, resistance to quinolones is
      primarily related to alterations in gyrA. Transformation with the full sequence
      of E. tarda gyrA bearing the Ser83 --> Arg mutation was able to complement the
      sequence of the gyrA temperature-sensitive mutation in the E. coli KNK453 strain
      and to induce increased resistance to quinolone antibiotics at 42 degrees C.

PMID- 16408844
TI  - IS2-mediated re-arrangement of the promoter sequence suppresses metabolic burden
      of the recombinant plasmid.
AB  - Recombinant plasmid pKA18 of the high expression bacterial system for penicillin
      amidase ('penicillin G acylase') bears the 3' end region of IS2 element. The IS2
      sequence replaces the -35 region of promoter of pga and extends up to TAGTAT box
      at position -10 of the promoter region. It therefore forms a hybrid promoter of
      pga ppgaHT. A natural promoter ppgaWT was not detected on any recombinant plasmid
      isolated from recombinant strains of Escherichia coli constitutively producing
      penicillin amidase. PCR fragments carrying both types of promoters were cloned
      into the promoter-probe vector pET2 to compare their transcriptional activity:
      the activity of ppgaWT was 5x higher than that of ppgaHT. The same nucleotide "G"
      localized 28 nucleotides upstream of the translation start point was identified
      as the respective transcription start point of both mRNAs. An attempt was made to
      place the pga gene cloned on a plasmid under the control of the natural promoter:
      not a single clone expressing penicillin amidase was found among 150
      transformants. High transcriptional activity of the natural promoter together
      with high pga gene dosage could result in a deleterious metabolic burden of the
      periplasmic enzyme.

PMID- 16408845
TI  - Inductive effects of environmental concentration of atrazine on Escherichia coli
      and Enterococcus faecalis.
AB  - Atrazine solutions (0.1, 1, 10 and 100 microg/L) inoculated with Escherichia coli
      and Enterococcus faecalis under natural conditions significantly increased (p <
      or = 0.05) the population levels of both test bacteria; it indicates the ability
      of bacterial cells to degrade atrazine and to use the original compound or its
      degradation products as nutrient(s). In some cases, alterations in the morphology
      of the colonies were also observed on selective solid media. Biochemical
      differentiation was also found and, on the other hand, a loss of culturability
      was recorded; this suggests that bacteria have entered in a viable but
      nonculturable state. A re-appearance of the colonies occurred after inoculation
      on tryptone-soy agar with atrazine.

PMID- 16408846
TI  - Molecular analysis of 16S-23S spacer regions of Acetobacter species.
AB  - 16S-23S rDNA internal transcribed spacer regions (ITS) similarities were
      determined in 8 Acetobacter and 1 Gluconacetobacter strains. ITS-PCR
      amplification of the 16S-23S spacers showed 2 products of similar size in 7
      strains; only 1 product of similar size was found in the 2 remaining strains.
      Analysis of the PCR products using restriction endonucleases HaeIII, HpaII and
      AluI revealed 3 different restriction groups of A. pasteurianus for AluI and
      HaeIII, and 4 restriction groups for HpaII. ITS nucleotide sequences of all
      studied strains exhibited a 52-98% similarity.

PMID- 16408847
TI  - Synthetic lethal interaction between the pel1 and op1 mutations in Saccharomyces
      cerevisiae.
AB  - The Saccharomyces cerevisiae mutant strain containing the op1 mutation affecting
      the function of a mitochondrial ATP/ADP translocator has been crossed to the pel1
      and crd1 mutants deficient in the biosynthesis of mitochondrial
      phosphatidylglycerol (PG) and cardiolipin (CL). Using tetrad analysis of diploids
      issued from corresponding crosses a synthetic lethal interaction has been
      observed between the op1 and pel1 mutations resulting in the lack of growth of a
      corresponding double mutant on minimal medium containing glucose. The op1 pel1
      double mutant also displayed a decreased susceptibility to fluconazole and a
      compromised growth even in complex medium containing glucose. The viability of
      mutant cells was strongly reduced, corresponding to <30 % and 10 % of colony
      forming units observed after growth in complex and minimal medium, respectively.
      A lower viability of the double mutant in minimal medium was accompanied by an
      increased formation of mitochondrial petite mutants (as determined by mtDNA
      rescue into diploid cells). The results indicate that in the simultaneous absence
      of mitochondrial anionic phospholipids (PG plus CL) and ATP/ADP exchange across
      the inner mitochondrial membrane the yeast mitochondrial functions are severely
      limited, leading to a strongly compromised cell multiplication. Since under
      similar conditions the op1 crd1 double mutant was able to grow on minimal medium
      this deleterious effect of anionic phospholipid deficiency could be at least
      partially substituted by PG accumulated in the cardiolipin deficient delta crd1
      mutant cells.

PMID- 16408848
TI  - Continuous aerobic phenol degradation by defined mixed immobilized culture in
      packed bed reactors.
AB  - A defined mixed culture of Pseudomonas putida, Commamonas testosteroni and
      Candida tropicalis was immobilized by adsorption on polyurethane foam, cocoa
      fibers, expanded slate and sintered glass. Packed bed reactors were used for long
      term continuous phenol biodegradations. Loading experiments were done to study
      the impact of the following parameters: (1) hydraulic retention time, (2)
      dissolved oxygen concentration, and (3) elimination of the oxygen limitation.
      After the acclimation period (approximately 10 d), the loading test with the
      individual packings showed the following maximum degradation rates: sintered
      glass 34, polyurethane foam 12, expanded slate 11.5, and cocoa-fibers 7.7 kg m(
      3) d(-1). All these values were reached at a removal efficiency >99 % and with
      oxygen in excess. Under these conditions, the pH of the diluted unbuffered medium
      in the reactor effluent was 3.2-4.0 and no incompletely oxidized metabolic
      intermediates were found. The free cell concentration in the effluent increased
      after the phenol overloading time period.

PMID- 16408849
TI  - Removal of copper ions from dilute solutions by Streptomyces noursei mycelium.
      Comparison with yeast biomass.
AB  - Sorption properties of Streptomyces noursei mycelium for copper ions were
      compared with the accumulation competence of dried and native yeast (Candida
      utilis) biomass. The copper sorption capacity of S. noursei after optimization
      was found to be higher than that of the two other adsorbents (dried yeast biomass
      82 %, native Candida cells 48 % of the sorption capacity of the S. noursei
      mycelium).

PMID- 16408850
TI  - Motility and survival of Euglena ignobilis as affected by different factors.
AB  - Euglena ignobilis cells in natural puddle water of pH 7.8, when kept at 21 +/- 2
      degrees C and under continuous light (intensity of approximately 30 micromol m(
      2) s(-1)) in a culture chamber, decreased their speed of movement from > or =
      78000 microm/min (after a 12-h cultivation), to 850-1300 microm/min after 18 h.
      Simultaneously initiated were changes in morphology from the usual elongated
      motile forms to round motile ones by curving and contraction. Water stress (2 and
      4 % agarized puddle water, puddle water with 0.2-1 mol/L NaCl), temperature shock
      (< or = 10 degrees C, > or = 30 degrees C), darkness and low-light intensity, UV
      exposure (0.96-2.88 kJ/m2), pH extremes (< or = 6.5 and > or = 10), presence of
      'heavy' metals (1-100 ppm Fe, Cu, Zn, Co, Ni, Hg) or organic substances in puddle
      water (25-1000 ppm 2,4-D, captan, urea, DDT, thiourea), all these factors rapidly
      (after 5 to 30 min) decreased the speed of the elongated motile form to < or =
      300 microm/min, and induced all morphological changes leading to formation of
      round motile and round nonmotile forms. These features in the alga (i.e. sudden
      speed reduction and morphological changes from elongate motile to round motile
      form) may thus be suggested to be used in assessing water quality.

PMID- 16408851
TI  - Visualization of nodulation gene activity on the early stages of Rhizobium
      leguminosarum bv. viciae symbiosis.
AB  - A technique was optimized for the in situ detection of nodulation (nod) gene
      activity in Rhizobium leguminosarum bv. viciae symbiosis with compatible plant
      hosts Vicia tetrasperma (L.) SCHREB. and Pisum sativum L. The transcription of
      nodABC-lacZ fusion was visualized as beta-galactosidase (beta-Gal) activity after
      reaction with the chromogenic substrate X-Gal and subsequent light microscopy,
      while the background of the indigenous beta-Gal activity of rhizobia and the host
      plant was eliminated by glutaraldehyde treatment. V. tetrasperma was suggested as
      a suitable model plant for pea cross-inoculation group due to its advantages over
      the common model of V. hirsuta (L.) S.F. GRAY: compactness of the plant,
      extremely small seeds, fast development and stable nodulation under laboratory
      conditions. In the roots of both plants, a certain extent of nod gene activity
      was detectable in all rhizobia colonizing the rhizoplane. In pea 1 d after
      inoculation (d.a.i.), the maximum was localized in the region of emerging root
      hairs (RH) later (3 and 6 d.a.i.) shifting upwards from the root tip. Nodulation
      genes sustained full expression even in the infection threads inside the RH and
      the root cortex, independently of their association with nodule primordia.
      Comparison of two pea symbiotic mutant lines, Risnod25 and Risnod27, with the
      wild type did not reveal any differences in the RH formation, RH curling response
      and rhizoplane colonization. Both mutants appeared to be blocked at the infection
      thread initiation stage and in nodule initiation, consistent with the phenotype
      caused by other mutant alleles in the pea sym8 locus. Judging from the nod gene
      expression level and pattern in the rhizoplane, flavonoid response upon
      inoculation is preserved in both pea mutants, being independent of infection
      thread and nodule initiation.

PMID- 16408852
TI  - Visualization of DNA-containing structures in various species of Chlorophyta,
      Rhodophyta and Cyanophyta using SYBR Green I dye.
AB  - We developed an alternative method of staining cell nuclei and chloroplast
      nucleoids of algal cells using SYBR Green I (the fluorescent dye used commonly
      for detecting dsDNA in agarose and polyacrylamide gels as an alternative to
      highly mutagenic ethidium bromide and for DNA staining of viruses and bacteria
      followed by flow cytometry, digital image analysis or real-time PCR), which
      enabled routine staining in vivo. Cells do not need to be fixed or treated
      chemically or physically before staining, thus the shape, size and position of
      DNA-containing structures are not affected. The fluorescence signal is sharp and
      reproducible. Examples of application of the method are shown in color
      microphotographs for representatives of eukaryotic algae from the taxa
      Chlorophyta, Rhodophyta and the prokaryotic Cyanophyta. The method is also useful
      for studying progress of the cell cycle in algal cells dividing by multiple
      fission, as shown by observation of changes in nuclear number during the cell
      cycle of the green alga Chlamydomonas reinhardtii and Scenedesmus quadricauda.
      Staining with SYBR Green I can be recommended as a fast, safe and efficient
      method for the detection of DNA-containing structures in vivo.

PMID- 16408853
TI  - Polymerase chain reaction for detection of Toxoplasma gondii in human biological
      samples.
AB  - Using the polymerase chain reaction (PCR), Toxoplasma gondii from gene TGR1E with
      primers TGR1E-1, TGR1E-2 (standard PCR), and from B1 gene with primers TM1, TM2,
      TM3 (hemi-nested PCR) was detected in biological samples from 347 individuals
      (441 biological materials). Of the total of 441 biological materials, T. gondii
      DNA was detected in 5.2 %; it was positive in the following samples: blood (n =
      6), blood from newborns (2), biopsies (2) and samples of progenitor cells (2)
      (from candidates for bone marrow transplantation). DNA of T. gondii was also
      revealed in 11 samples (8.3 %) of 120 cases of pregnant women during prenatal
      examinations. A positive result in the blood was also found in two cases of
      newborn babies from mothers who were infected in later pregnancy. The positive
      PCR examination was confirmed by serological methods (ELISA and complement
      fixation test). Agreement of PCR results and the detection of antibodies against
      toxoplasma was found in 83.3 %. Rapid PCR examination for the confirmation of
      acute parasitemia T. gondii is particularly important for the patients in whom
      the infection may cause serious consequences (e.g., for fetus in pregnant women
      or for patients suffering from imunosuppression).

PMID- 16408854
TI  - Laboratory diagnosis of leptospirosis.
AB  - Percentage of serological positivity examined in 4205 blood sera by serological
      method microscopic agglutination test (MAT) on the hinterland territory of our
      laboratory (East Bohemia; 1999-2003) was 0.38-4.7 %. By the PCR method for
      detection of DNA of pathogenic leptospires (L. interrogans, L. borgpetersenii and
      L. kirschneri) from 57 samples of different biological materials from patients
      with fever of unknown etiology positive results were obtained in 4 specimens (7
      %; 3 samples of urine and 1 sample of blood). This method was shown to
      distinguish between pathogenic and nonpathogenic strains and can detect 2.5-10
      cells per mL of biological material. As an important presumption of successful
      detection of pathogenic leptospires a correct collecting of blood, urine samples
      or liquor is required before starting antibody therapy. The PCR method possesses
      a clear advantage over other methods, such as MAT, which relies on the detection
      of antibodies the presence of which cannot be detected until days after
      infection.

PMID- 16408855
TI  - Seasonal dynamics of antibiotic-resistant Enterobacteriaceae in the
      gastrointestinal tract of domestic sheep.
AB  - Considerable variation in counts of antibiotic-resistant enterobacteria in the
      ovine gastrointestinal tract was observed. The occurrence of ruminal and fecal
      isolates resistant to ampicillin (Ap), kanamycin (Km) and tetracycline (Tc)
      culminated in summer months, followed by rapid decline in subsequent months.
      Using PCR the tem1bla (Apr), aphA1 (Kmr) and tetB (Tcr) genes were found to be
      predominant. Under in vitro conditions all resistance genes were transferable
      into laboratory Escherichia coli strain with relatively high frequency (10(-3)
      transconjugants per recipient).

PMID- 16408856
TI  - The effects of organic selenium supplementation on the rumen ciliate population
      in sheep.
AB  - The effect of selenium supplementation on the rumen protozoan population of sheep
      was demonstrated. Both the total and generic counts of rumen ciliates in sheep
      fed a diet with basal Se content (70 microg/kg dry matter) were compared to those
      of animals given feed supplemented with inorganic (disodium selenite) or organic
      Se (selenized yeast) (310 microg/kg dry matter). The genera of Entodinium,
      Isotricha, Dasytricha, Ophryoscolex, Diploplastron and Polyplastron occurred in
      all sheep except for the control, in which Ophryoscolex was not observed. The
      population of Ophryoscolex caudatus f. tricoronatus was significantly higher in
      sheep supplemented with organic Se than in animals given inorganic Se (by 160 %).
      Supplementation of feed with selenized yeast induced significant growth in the
      Diploplastron population (by 63 %) while no change occurred in sheep given
      selenite. The populations of Dasytricha ruminantium and Polyplastron
      multivesiculatum were higher than control in both Se-supplemented groups. The
      ciliate population of Entodinium spp. was not influenced by Se supplements. Our
      results suggest a protective effect of Se feed supplementation on the development
      of some rumen ciliate species in young ruminants.

PMID- 16408857
TI  - A model-dependent approach to correlate accelerated with real-time release from
      biodegradable microspheres.
AB  - The purpose of this study was to determine the feasibility of applying
      accelerated in vitro release testing to correlate or predict long-term in vitro
      release of leuprolide poly(lactide-co-glycolide) microspheres. Peptide release
      was studied using a dialysis technique at 37 degrees C and at elevated
      temperatures (50 degrees C-60 degrees C) in 0.1M phosphate buffered saline (PBS)
      pH 7.4 and 0.1M acetate buffer pH 4.0. The data were analyzed using a
      modification of the Weibull equation. Peptide release was temperature dependent
      and complete within 30 days at 37 degrees C and 3 to 5 days at the elevated
      temperatures. In vitro release profiles at the elevated temperatures correlated
      well with release at 37 degrees C. The shapes of the release profiles at all
      temperatures were similar. Using the modified Weibull equation, an increase in
      temperature was characterized by an increase in the model parameter, alpha, a
      scaling factor for the apparent rate constant. Complete release at 37 degrees C
      was shortened from approximately 30 days to 5 days at 50 degrees C, 3.5 days at
      55 degrees C, 2.25 days at 60 degrees C in PBS pH 7.4, and 3 days at 50 degrees C
      in acetate buffer pH 4.0. Values for the model parameter beta indicated that the
      shape of the release profiles at 55 degrees C in PBS pH 7.4 (2.740) and 50
      degrees C in 0.1M acetate buffer pH 4.0 (2.711) were similar to that at 37
      degrees C (2.677). The E(a) for hydration and erosion were determined to be 42.3
      and 19.4 kcal/mol, respectively. Polymer degradation was also temperature
      dependent and had an E(a) of 31.6 kcal/mol. Short-term in vitro release studies
      offer the possibility of correlation with long-term release, thereby reducing the
      time and expense associated with long-term studies. Accelerated release
      methodology could be useful in the prediction of long-term release from extended
      release microsphere dosage forms and may serve as a quality control tool for the
      release of clinical or commercial batches.

PMID- 16408858
TI  - In vitro and in vivo evaluation of topical formulations of spantide II.
AB  - The purpose of this study was to develop and evaluate topical formulations of
      Spantide II, a neurokinin-1 receptor (NK-1R) antagonist, for the treatment of
      inflammatory skin disorders. Spantide II lotion and gel was formulated with and
      without n-methyl-2-pyrrolidone (NMP) as a penetration enhancer. The release of
      Spantide II from gels was evaluated using microporous polyethylene and
      polypropylene membranes in a Franz Diffusion cell setup. In vitro percutaneous
      absorption of Spantide II from lotion and gel formulations was evaluated using
      the above setup by replacing the membranes with hairless rat skin. The in vivo
      anti-inflammatory activity of Spantide II formulations was evaluated in an
      allergic contact dermatitis (ACD) mouse model. Among different gels studied,
      PF127 gel showed highest (70-fold) release of Spantide II compared with
      hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) gels.
      Lotion and gel formulations with or without NMP showed no detectable levels of
      Spantide II in the receiver compartment of the Franz diffusion cell until 24
      hours. However, Spantide II showed significant retention in epidermis and dermis
      from lotion and gel formulations at 24 hours. The dermal levels increased
      approximately 3.5- and 2-fold when the lotion and gel formulations contained NMP
      as compared with the formulation with no NMP (P < .05). The in vivo studies
      indicated that Spantide II formulations with NMP were effective in significantly
      reducing ACD response, similar to dexamethasone (0.5 mM). In conclusion, Spantide
      II was stable as a topical formulation and delivered to target skin tissue
      (epidermis and dermis) for the treatment of ACD. In addition this study supports
      the role of cutaneous neurosensory system in modulating inflammatory responses in
      the skin.

PMID- 16408859
TI  - Box-Behnken experimental design in the development of a nasal drug delivery
      system of model drug hydroxyurea: characterization of viscosity, in vitro drug
      release, droplet size, and dynamic surface tension.
AB  - The purpose of the research was to investigate the changes in physicochemical
      properties and their influence on nasal formulation performance using 5-factor, 3
      level Box-Behnken experimental design on the combined responses of viscosity,
      droplet size distribution (DSD), and drug release. Gel formulations of
      hydroxyurea (HU) with surface-active polymers (hydroxyethylcellulose [HEC] and
      polyethylene-oxide [PEO]) and ionic excipients (sodium chloride and calcium
      chloride) were prepared using Box-Behnken experimental design. The rheology and
      dynamic surface tension (DST) of the test formulations was investigated using LV
      DV-III Brookfield rheometer and T60 SITA tensiometer, respectively. Droplet size
      analysis of nasal aerosols was determined by laser diffraction using the Malvern
      Spraytec with the InnovaSystems actuator. In vitro drug release studies were
      conducted on Franz diffusion cells. With PEO gel, calcium chloride increased the
      viscosity and DSD and retarded drug release, while sodium chloride decreased the
      viscosity, DST, and DSD and accelerated the release of HU. With HEC gel, the
      addition of the above salts resulted in less significant changes in viscosity,
      DSD, and DST, but both salts significantly increased the release of HU. Droplet
      size data obtained from a high viscosity nasal pump was dependent on type of
      polymer, polymer-excipient interactions, and solvent properties. The applications
      of Box-Behnken experimental design facilitated the prediction and identified
      major excipient influences on viscosity, DSD, and in vitro drug release.

PMID- 16408860
TI  - Comparison between gamma and beta irradiation effects on
      hydroxypropylmethylcellulose and gelatin hard capsules.
AB  - The effects of electron beam or gamma-irradiation on technological performances
      (capsule hardness, expressed as deforming work and dissolution time) of empty 2
      shell capsules made of gelatin or hydroxypropylmethylcellulose (HPMC) were
      studied. Capsule structural changes induced by radiation treatment were
      investigated by capillary viscometry and atomic force microscopy (AFM). The
      capsules were irradiated in the air at 5, 15, and 25 kGy. The deforming work of
      nonirradiated HPMC capsules (0.06 +/- 0.01 J) was lower than that of gelatin
      capsules (0.10 +/- 0.01 J). The dissolution time of the HPMC capsules (414 +/- 33
      seconds) was slightly higher than that determined for gelatin hard capsules (288
      +/- 19 seconds). The hardness and dissolution time of gelatin and HPMC capsules
      were not significantly influenced by the irradiation type and the applied
      irradiation dose. As the viscometry analyses are concerned, irradiation caused a
      reduction of the intrinsic viscosity and water and dimethyl sulfoxide solvent
      power in both the cases. AFM analysis showed that the radiation treatment did not
      appreciably affect the surface roughness of the samples nor induce structural
      changes on capsule surface. However, measurements of force-distance curves
      pointed out a qualitative parameter for the identification of the irradiated
      capsules. On the bases of these preliminary results, empty gelatin or HPMC hard
      capsules can be sanitized/sterilized by ionizing radiation.

PMID- 16408861
TI  - Nanoprecipitation versus emulsion-based techniques for the encapsulation of
      proteins into biodegradable nanoparticles and process-related stability issues.
AB  - The goal of this study was to investigate the entrapment of 3 different model
      proteins (tetanus toxoid, lysozyme, and insulin) into poly(D,L-lactic acid) and
      poly(D,L-lactic-co-glycolic acid) nanoparticles and to address process-related
      stability issues. For that purpose, a modified nanoprecipitation method as well
      as 2 emulsion-based encapsulation techniques (ie, a solid-in oil-in water (s/o/w)
      and a double emulsion (w(1)/o/w(2)) method) were used. The main modification of
      nanoprecipitation involved the use of a wide range of miscible organic solvents
      such as dimethylsulfoxide and ethanol instead of the common acetone and water.
      The results obtained showed that tetanus toxoid and lysozyme were efficiently
      incorporated by the double emulsion procedure when ethyl acetate was used as
      solvent (>80% entrapment efficiency), whereas it was necessary to use methylene
      chloride to achieve high insulin entrapment efficiencies. The use of the s/o/w
      method or the formation of a more hydrophobic protein-surfactant ion pair did not
      improve protein loading. The nanoprecipitation method led to a homogenous
      population of small nanoparticles (with size ranging from approximately 130 to
      560 nm) and in some cases also improved experimental drug loadings, especially
      for lysozyme (entrapment efficiency > 90%). With respect to drug content
      determination, a simple and quick matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) method provided results very
      close to those obtained by reverse phase-high-performance liquid chromatography.
      With respect to protein stability, the duration and intensity of sonication were
      not a concern for tetanus toxoid, which retained more than 95% of its
      antigenicity after treatment for 1 minute. Only a high methylene chloride:water
      ratio was shown to slightly decrease toxoid antigenicity. Finally, no more than
      3.3% of A21 desamido insulin and only traces of covalent insulin dimer were
      detected in nanoparticles. In conclusion, both the double emulsion and
      nanoprecipitation methods allowed efficient protein encapsulation. MALDI-TOF MS
      allowed accurate drug content determination. The manufacturing processes
      evaluated did not damage the primary structure of insulin.

PMID- 16408862
TI  - Encapsulation of protein nanoparticles into uniform-sized microspheres formed in
      a spinning oil film.
AB  - A new spinning oil film (SOF) solid-in-oil-in-oil emulsion process was developed
      to produce uniform-sized protein-loaded biodegradable microspheres. A thin SOF on
      a cylindrical rotor was used to shear droplets from a nozzle tip to control
      droplet size. The resulting microspheres with low polydispersity (6%) produced a
      low burst (6%-11%) release even at high loadings (13%-18% encapsulated solids, 8%
      12% protein). The SOF process had a high yield and did not require the presence
      of water, which can cause protein denaturation, or surfactants, which may be
      unwanted in the final product. Amorphous protein and crystalline excipient solids
      were encapsulated into 3 different polymers, giving a homogenous drug
      distribution throughout the microspheres, and an essentially complete protein
      encapsulation efficiency (average = 99%). In contrast, large burst release was
      observed for polydisperse microspheres produced by a conventional emulsification
      technique, particularly for microspheres smaller than 25 mum in diameter, which
      gave 93% burst at 15% loading. The uniform encapsulation of high loadings of
      proteins into microspheres with low polydispersity in an anhydrous process is of
      practical interest in the development of controlled-release protein therapeutics.

PMID- 16408863
TI  - Adsorption of meloxicam on porous calcium silicate: characterization and tablet
      formulation.
AB  - The purpose of the present study was characterization of microparticles obtained
      by adsorption of poorly water soluble drug, meloxicam, on a porous silicate
      carrier Florite RE (FLR) and development of a tablet formulation using these
      microparticles, with improved drug dissolution properties. The study also reveals
      the use of FLR as a pharmaceutical excipient. Meloxicam was adsorbed on the FLR
      in 2 proportions (1:1 and 1:3), by fast evaporation of solvent from drug solution
      containing dispersed FLR. Drug adsorbed FLR microparticles were evaluated for
      surface topography, thermal analysis, X-ray diffraction properties, infrared
      spectrum, residual solvent, micromeritic properties, drug content, solubility,
      and dissolution studies. Microparticles showed bulk density in the range of 0.10
      to 0.12 g/cm(3). Dissolution of drug from microparticles containing 1:3, drug:FLR
      ratio was faster than microparticles containing 1:1, drug:FLR ratio. These
      microparticles were used for formulating directly compressible tablets. Prepared
      tablets were compared with a commercial tablet. All the prepared tablets showed
      acceptable mechanical properties. Disintegration time of prepared tablets was in
      the range of 18 to 38 seconds, and drug dissolution was much faster in both
      acidic and basic medium from prepared tablets as compared with commercial tablet.
      The results suggest that FLR provides a large surface area for drug adsorption
      and also that a reduction in crystallinity of drug occurs. Increase in surface
      area and reduction in drug crystallinity result in improved drug dissolution from
      microparticles.

PMID- 16408864
TI  - Design and evaluation of 1- and 3-layer matrices of verapamil hydrochloride for
      sustaining its release.
AB  - The present study was performed to design oral controlled delivery systems for
      the water-soluble drug, verapamil hydrochloride, using natural and semisynthetic
      polymers as carriers in the forms of 1- and 3-layer matrix tablets. Verapamil
      hydrochloride 1-layer matrix tablets containing hydroxypropylmethylcellulose,
      tragacanth, and acacia either alone or mixed were prepared by direct compression
      technique. 3-layer matrix tablets were prepared by compressing the polymers as
      release retardant layers on both sides of the core containing the drug. The
      prepared tablets were subjected to in vitro drug release studies. Tragacanth when
      used as the carrier in the formulation of 1- and 3-layer matrices produced
      satisfactory release prolongation either alone or in combination with the other 2
      polymers. On the other hand, acacia did not show enough prolonging efficiency in
      1- and 3-layer matrix tablets. The results also showed that the location of the
      polymers in the 3-layer tablets has a pronounced effect on the drug release.
      Kinetic analysis of drug release from matrices exhibiting sustained release
      indicated that release was predominantly attributable to the contribution made by
      Fickian diffusion, while the erosion/relaxation mechanisms had a minor role in
      the release.

PMID- 16408865
TI  - Functionality comparison of 3 classes of superdisintegrants in promoting aspirin
      tablet disintegration and dissolution.
AB  - The aims of this study are (1) to compare the disintegration efficiency, and (2)
      to develop a discriminating test model for the 3 classes of superdisintegrants
      represented by Ac-Di-Sol, Primojel, and Polyplasdone XL10. Using a digital video
      camera to examine the disintegration process of tablets containing the same wt/wt
      percentage concentration of the disintegrants, Ac-Di-Sol was found to
      disintegrate tablets rapidly into apparently primary particles; Primojel also
      apparently disintegrated tablets into primary particles but more slowly;
      Polyplasdone XL10 disintegrated tablets rapidly but into larger masses of
      aggregated particles. The differences in the size distribution generated in the
      disintegrated tablets likely contribute to the drug dissolution rate differences
      found for aspirin tablets with similar disintegration rates. The aspirin tablet
      matrix is proposed as a model formulation for disintegrant efficiency comparison
      and performance consistency testing for quality control purposes.

PMID- 16408867
TI  - Evaluation of polymerized rosin for the formulation and development of
      transdermal drug delivery system: a technical note.

PMID- 16408866
TI  - Liposomal dry powders as aerosols for pulmonary delivery of proteins.
AB  - The purpose of this research was to develop liposomal dry powder aerosols for
      protein delivery. The delivery of stable protein formulations is essential for
      protein subunit vaccine delivery, which requires local delivery to macrophages in
      the lungs. Beta-glucuronidase (GUS) was used as a model protein to evaluate dry
      powder liposomes as inhaled delivery vehicles. Dimyristoyl
      phosphatylcholine:cholesterol (7:3) was selected as the liposome composition. The
      lyophilization of liposomes, micronization of the powders, aerosolization using a
      dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon
      collection in a twin-stage liquid impinger were evaluated. After lyophilization
      and jet-milling, the total amount of GUS and its activity, representing
      encapsulation efficiency and stability, were evaluated. The GUS amount and
      activity were measured and compared with freshly-prepared liposomes in the
      presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after
      lyophilization and 36% of GUS amount, 22% of activity after micronization were
      obtained. Emitted doses from dry powder inhaler were 53%, 58%, 66%, and 73% for
      liposome powder:mannitol carrier ratios of 1:0, 1:4, 1:9, and 1:19. Fifteen
      percent of the liposome particles were less than 6.4 mum in aerodynamic diameter.
      The results demonstrate that milled liposome powders containing protein molecules
      can be aerosolized effectively at a fixed flow rate. Influences of different
      cryoprotectants on lyophilization of protein liposome formulations are reported.
      The feasibility of using liposomal dry powder aerosols for protein delivery has
      been demonstrated but further optimization is required in the context of specific
      therapeutic proteins.

PMID- 16408868
TI  - The crystal structure and physicochemical characteristics of 2-hydroxy-N-[3(5)
      pyrazolyl]-1,4-naphthoquinone-4-imine, a new antitrypanosomal compound.
AB  - This study was designed to investigate the physical characteristics and
      crystalline structure of 2-hydroxy-N-[3(5)-pyrazolyl]-1,4-naphthoquinone-4-imine
      (PNQ), a new active compound against Trypanosoma cruzi, the causative agent of
      American trypanosomiasis. Methods used included differential scanning
      calorimetry, thermogravimetry, hot stage microscopy, polarized light microscopy
      (PLM), Fourier-transform infrared (FTIR) spectroscopy, and high-resolution X-ray
      powder diffraction (HR-XRPD). According to PLM and HR-XRPD data, PNQ crystallized
      as red oolitic crystals (absolute methanol) or prisms (dimethyl sulfoxide [DMSO]
      water) with the same internal structure. The findings obtained with HR-XRPD data
      (applying molecular location methods) showed a monoclinic unit cell [a =
      18.4437(1) A, b = 3.9968(2) A, c = 14.5304(1) A, alpha = 90 degrees , beta =
      102.71(6) degrees , gamma = 90 degrees , V = 1044.9(1) A(3), Z = 4, space group
      P2(1)/c], and a crystal structure (excluding H-positions) described by parallel
      layers in the direction of the b-axis, with molecules held by homochemical
      (phenyl-phenyl and pyrazole-pyrazole) van der Waals interactions. In addition,
      FTIR spectra displayed the NH-pyrazole stretch overlapped with the OH absorption
      at 3222 cm(-1), typical of -NH and -OH groups associated through H-bondings; and
      a carbonyl stretching absorption at 1694 cm(-1), indicating a nonextensively H
      bonded quinonic C=O, which was in accordance with the solved crystal structure of
      PNQ. The existence of such cohesive forces shed light on the thermoanalytical
      data, which revealed that PNQ is a stable solid, unaffected by oxygen that
      decomposed without melting above 260 degrees C.

PMID- 16408869
TI  - Synthesis of nicotine derivatives via reductive disilylation of (S)-nicotine.
AB  - [reaction: see text] A variety of novel nicotine derivatives were prepared via
      reductive disilylation of (S)-nicotine. Treatment of nicotine with lithium powder
      and chlorotrimethylsilane afforded 1,4-bis(trimethylsilyl)-1,4-dihydronicotine in
      high yield. Addition of various carbonyl electrophiles and a catalytic amount of
      TBAF provided either C-5 substituted nicotines or 1,4-dihydronicotine
      derivatives.

PMID- 16408870
TI  - An 11 nm molecular wire that switches electrochemically between an insulating and
      a fully conjugated conducting state.
AB  - [structure: see text] Molecular wires consisting of oligothiophenes and
      oligothiophenylethynes, ranging in length from 2 to 11 nm, are synthesized and
      examined by spectroscopy and electrochemistry. UV spectroscopy shows that the
      longest wires are not fully conjugated, but twisted. However, cyclic voltammetry
      indicates that their monocations are now flattened and conjugated over the entire
      length range. In appropriate systems, the wires will link to two electrodes
      across a nanoscale gap and conduct current.

PMID- 16408871
TI  - Difluoromethylenediphosphonate: a convenient, scalable, and high-yielding
      synthesis.
AB  - [reaction: see text] Since the first disclosure of
      difluoromethylenediphosphonate, 2, almost 40 years ago, interest in this compound
      has flourished in several research areas. In this paper, we present a convenient,
      high-yielding (99% overall) method for the preparation of milligram to multigram
      quantities of 2 (as the bis(tributylammonium salt, 2b) in a solid form that is
      easy to handle.

PMID- 16408873
TI  - Indium-mediated one-pot three-component reaction of aromatic amines, enol ethers,
      and allylic bromides.
AB  - [reaction: see text] A new and efficient indium-mediated one-pot three-component
      reaction for the synthesis of N-aryl-substituted homoallylamines from aromatic
      amines, enol ethers, and allylic bromides in THF at room temperature is
      described.

PMID- 16408874
TI  - On the mechanism of DABCO-catalyzed isomerization of gamma-hydroxy-alpha,beta
      alkynoates to gamma-oxo-alpha,beta-(E)-alkenoates.
AB  - [reaction: see text] Since the discovery of organic base-catalyzed isomerization
      of gamma-hydroxy-alpha,beta-acetylenic esters to gamma-oxo-alpha,beta-trans
      alkenyl esters in 1949, the mechanism has not been elucidated. This study shows
      that the mechanism involves cumulene formation, protonation with the conjugate
      acid of the amine, and protonation of the resulting allenol with water.

PMID- 16408872
TI  - A Lewis acid-catalyzed formal [3 + 3] cycloaddition of alpha,beta-unsaturated
      aldehydes with 4-hydroxy-2-pyrone, diketones, and vinylogous esters.
AB  - [reaction: see text] A Lewis acid-catalyzed formal cycloaddition of alpha,beta
      unsaturated aldehydes with 6-methyl-4-hydroxy-2-pyrone, 1,3-diketones, and
      vinylogous silyl esters is described here.

PMID- 16408875
TI  - A general strategy for the facile synthesis of 2,7-dibromo-9-heterofluorenes.
AB  - [reaction: see text] A facile, highly efficient, and economical procedure for the
      preparation of 6,6'-diiodo-4,4'-dibromo-3,3'-dimethoxylbiphenyl has been found.
      From this compound, a general synthetic strategy for the preparation of 2,7
      dibromo-9-heterofluorenes has been developed. Five 2,7-dibromo-9-heterofluorenes
      have been easily synthesized for the first time according to the procedure
      presented, opening the door to new classes of inorganic and organometallic
      conjugated polymeric materials of polyheterofluorenes.

PMID- 16408876
TI  - Carbohydrate-derived amino-alcohol ligands for asymmetric alkynylation of
      aldehydes.
AB  - [reaction: see text] Conformationally restricted amino alcohols based on
      carbohydrate scaffolds provide flexible and fine-tuneable libraries that greatly
      expand the range of ligands available in the Zn(OTf)(2)-mediated addition of
      alkynes to aldehydes, in some cases with very high stereoselectivities.

PMID- 16408877
TI  - Novel triptycene-based cylindrical macrotricyclic host: synthesis and
      complexation with paraquat derivatives.
AB  - [reaction: see text] A novel triptycene-based cylindrical macrotricyclic
      polyether containing two dibenzo[24]crown-8 cavities has been synthesized and
      proved to be a highly efficient host for the complexation with paraquat
      derivatives. Consequently, a new kind of very stable pseudorotaxane-type complex
      was formed in solution and in the solid state.

PMID- 16408878
TI  - Oxazaphospholidine-oxide as an efficient ortho-directing group for the
      diastereoselective deprotonation of ferrocene.
AB  - [reaction: see text] Ortho-lithiation of (2R,4S,5R)-3,4-dimethyl-2-ferrocenyl-5
      phenyl[1,3,2]oxazaphospholidine 2-oxide 2 was carried out with
      diastereoselectivity of >99%, affording a new and efficient way for introducing
      planar chirality into the ferrocene backbone. Various electrophiles were used to
      quench the lithiated species, showing the wide applicability of the new ortho
      directing group and its potential to generate ligands for use in asymmetric
      catalysis.

PMID- 16408879
TI  - Molecules at close range: encapsulated solvent molecules in pyrogallol[4]arene
      hexameric capsules.
AB  - [reaction: see text] Pyrogallol[4]arenes form hexameric capsules with a large
      cavity and can be regarded as nanoreactors. The (1)H NMR signals of the
      encapsulated chloroform and benzene molecules are very complex, which may
      indicate that these encapsulated molecules are trapped in slightly different
      capsules. Co-encapsulation was found to be favored, and the ASIS effect was found
      to be enhanced, probably due to the close proximity and the higher molecular
      fraction of the benzene/chloroform complex in the capsule.

PMID- 16408880
TI  - Arylamide derivatives as peptidomimetic inhibitors of calmodulin.
AB  - [structure: see text] Many peptides bind to calmodulin (CaM) in a helical
      conformation. Here we describe a group of synthetic inhibitors of CaM based on an
      arylamide scaffold that is intended to mimic smMLCK, a CaM-binding helical
      peptide. Compound 1 showed a K(i) value of 7.10 +/- 1.48 nM in a fluorescence
      polarization assay that monitors the strong association of CaM and its peptide
      ligand mastoparan X. ((1)H,(15)N)-HSQC NMR spectroscopy experiments suggested
      that 1 binds to CaM in an analogous fashion to that of smMLCK.

PMID- 16408881
TI  - Design and synthesis of novel chiral spiro ionic liquids.
AB  - [reaction: see text] Novel chiral imidazolium salts have been synthesized as
      examples of chiral ionic liquids with a spiro skeleton. Effects of N-substituents
      and counteranions on the melting point of spiro imidazolium salts and their
      chiral discrimination abilities are described.

PMID- 16408882
TI  - A ring-closing yne-carbonyl metathesis of ynamides.
AB  - [reaction: see text] An acid-catalyzed ring-closing ynamide-carbonyl metathesis
      is described here. This hetero RCM methodology is applicable to the construction
      of carbocycles as well as heterocycles such as chromenes, quinolizidines,
      indolizidines, and pyrrolizidines.

PMID- 16408883
TI  - Chirality control in oligothiophene through chiral wrapping.
AB  - [structure: see text] Mixing oligothiophenes and polysaccharides, such as amylose
      and schizophyllan, affords novel inclusion complexes, in which oligothiophene
      guests adopt twisted conformation in the chiral channel created by left- or right
      handed helical wrapping with the polysaccharide host polymers, leading to optical
      activity.

PMID- 16408884
TI  - Diastereoselective cationic tandem cyclizations to N-heterocyclic scaffolds:
      total synthesis of (-)-dysibetaine PP.
AB  - [reaction: see text] Herein, we report a short and diastereoselective synthesis
      of the natural product (-)-dysibetaine PP. The key step in the synthetic sequence
      is a novel highly diastereoselective tandem-cyclization reaction of an
      enantiomerically pure dipeptide. This cyclization methodology is applied in the
      synthesis of a broader range of N-heterocyclic scaffolds.

PMID- 16408885
TI  - Selective endo and exo iodocyclizations in the synthesis of quinolines and
      indoles.
AB  - [reaction: see text] A simple, efficient method for a divergent synthesis of
      indoles, quinolines, and quinolinones using a highly selective endo/exo
      iodocyclization procedure is described.

PMID- 16408886
TI  - An efficient synthesis of (+/-)-Lycoricidine featuring a Stille-IMDAF
      cycloaddition cascade.
AB  - [reaction: see text] A highly efficient total synthesis of (+/-)-Lycoricidine is
      described. The synthesis features the ready preparation of the Lycoricidine
      skeleton by a Stille-IMDAF cycloaddition cascade. The resulting cycloadduct is
      then used for the stereocontrolled installation of the other functionality
      present in the C-ring of the target molecule.

PMID- 16408887
TI  - Metal coordination-directed hydroxylation of steroids with a novel artificial P
      450 catalyst.
AB  - [structure: see text] A novel catalyst has been synthesized in which a manganese
      porphyrin unit is linked to two 2,2'-bipyridyl groups and two pentafluorophenyl
      groups in trans fashion on its four meso positions. Relative to a previous
      catalyst in which the manganese-porphyrin had four 2,2'-bipyridyl groups, the new
      catalyst, in the presence of Cu(2+) ions as coordinating linkers, catalyzes the
      oxidation of a steroid substrate with much better regioselectivity and higher
      turnover numbers.

PMID- 16408888
TI  - A novel convenient synthesis of benzoquinazolines.
AB  - [reaction: see text] A novel synthetic pathway to benzoquinazolines from
      naphthylamines is reported. Benzoquinazoline nucleus was cyclized in good yield
      from N-protected naphthylamines using hexamethylenetetramine in TFA and potassium
      ferricyanide in aqueous ethanolic KOH. This method is efficient and convenient
      with respect to previously reported synthetic pathways.

PMID- 16408889
TI  - Dispirofluorene-indenofluorene (DSFIF): synthesis, electrochemical, and optical
      properties of a promising new family of luminescent materials.
AB  - [reaction: see text] A series of new dispiro[fluorene-9',6,9' ',12
      indeno[1,2b]fluorenes] (DSFIFs) that combine indenofluorene (IF) and
      spirobifluorene (SBF) architectural specificities have been prepared. Their
      anodic oxidations lead to the formation of nonsoluble transparent polymers. The
      photophysical and electrochemical properties of these new molecules have been
      evaluated for further blue OLED applications.

PMID- 16408890
TI  - Formation of arylboronates by a CuI-catalyzed coupling reaction of pinacolborane
      with aryl iodides at room temperature.
AB  - [reaction: see text] The coupling reaction of pinacolborane with aryl iodides
      under the catalysis of 10 mol % CuI and the action of sodium hydride in THF works
      at room temperature to provide corresponding arylboronates in good yields. Aryl
      bromides give poor conversion under these reaction conditions.

PMID- 16408891
TI  - New latent fluorophore for DT diaphorase.
AB  - [reaction: see text] This study describes the design and synthesis of a novel
      latent fluorophore 3 for DT diaphorase based on the trimethyl lock effect and
      characterization of its enzymatic kinetics. Fluorophore 3 is also a sensitive
      fluorimetric reagent for detecting glucose when coupled with DTD and glucose
      dehydrogenase.

PMID- 16408892
TI  - An efficient route to 4-aryl-5-pyrimidinylimidazoles via sequential
      functionalization of 2,4-dichloropyrimidine.
AB  - [reaction: see text] Starting from 2,4-dichloropyrimidine, a concise synthetic
      route to medicinally important 4-aryl-5-pyrimidinylimidazoles is described.
      Sequential substitution of the 4- and 2-chloro groups using a regioselective
      Sonogashira coupling, followed by nucleophilic substitution, led to
      pyrimidinylalkyne derivatives, which were then oxidized to their corresponding
      1,2-diketones. These 1,2-diketones, on cyclocondensation with ammonium acetate
      and an aldehyde, furnished the desired pyrimidinyl imidazoles in good overall
      yields.

PMID- 16408893
TI  - Syntheses of soluble, pi-stacking tetracene derivatives.
AB  - [reaction: see text] The syntheses of a series of fluorine- and alkyl/alkoxy
      functionalized tetracenes are reported. These functional groups are found to
      improve the solubility in common organic solvents and tune molecular arrangement
      in solids. The crystal packing, electrochemical behavior, and UV-vis absorbance
      spectroscopy of these materials are discussed.

PMID- 16408894
TI  - Preparation of fullerendione through oxidation of vicinal fullerendiol and
      intramolecular coupling of the dione to form hemiketal/ketal moieties.
AB  - [reaction: see text] Vicinal fullerendiol is oxidized to fullerendione in good
      yield by (diacetoxy)iodobenzene. The resulting cage-opened fullerendione reacts
      with oxygen nucleophiles in the presence of BF(3).Et(2)O to form fullerene
      hemiketal/ketal derivatives through coupling of the two carbonyl groups.
      Fullerene-mixed peroxide derivatives are involved in all these reactions. The
      compounds are characterized by spectroscopic data and single-crystal X-ray
      analysis.

PMID- 16408895
TI  - Unusual highly regioselective direct aldol additions with a moisture-resistant
      and highly efficient titanium catalyst.
AB  - [reaction: see text] The extremely robust and water-stable tetranuclear complex
      Ti(4)(mu-BINOLato)(6)(mu(3)-OH)(4) was found to catalyze the direct aldol
      addition with high regioselectivities at the more steric alpha-encumbered side of
      unsymmetrical ketones. As few as 0.2 mol % loadings with this cluster were enough
      to afford complete conversions. The reaction proceeds very smoothly without a
      significant amount of byproducts. The formation of quaternary stereocenters is
      described.

PMID- 16408896
TI  - Reversible photoregulation of helical structures in short peptides under indoor
      lighting/dark conditions.
AB  - [reaction: see text] A photochromic cross-linking agent with a spiropyran
      skeleton was developed for the reversible photoregulation of helical structures
      in short peptides. The helical contents of the cross-linked peptides could be
      regulated by ambient light and dark conditions at room temperature. This
      switching of the helical contents could be repeated several times without
      substantial loss of any activity.

PMID- 16408897
TI  - Pt(II)- or Au(III)-catalyzed [3+2] cycloaddition of metal-containing azomethine
      ylides: highly efficient synthesis of the mitosene skeleton.
AB  - [reaction: see text] Only 1-3 mol % of PtCl(2) or AuBr(3) was sufficient to
      promote generation and [3+2] cycloaddition of transition-metal-containing
      azomethine ylides derived from N-(o-alkynylphenyl)imines bearing an internal
      alkyne moiety. A highly efficient method for the preparation of synthetically
      useful tricyclic indole derivatives having a substituent at the 3-position of the
      indole nucleus was established by this method.

PMID- 16408898
TI  - De novo asymmetric synthesis of homoadenosine via a palladium-catalyzed N
      glycosylation.
AB  - [reaction: see text] A highly stereoselective synthesis of l-2-deoxy-beta-ribo
      hexopyranosyl nucleosides from 6-chloropurine and Boc-protected pyranone has been
      developed. Our approach relies on the iterative application of a palladium
      catalyzed N-glycosylation, diastereoselective reduction, and reductive 1,3
      transposition. This strategy is amenable to prepare various natural and unnatural
      hexopyranosyl nucleosides analogues.

PMID- 16408899
TI  - Intramolecular benzyl protection delivery: a practical synthesis of DMDP and DGDP
      from D-fructose.
AB  - [reaction: see text] A two-step protection of 1,2-diols as the corresponding o
      xylylene cyclic ethers, involving an intramolecular ring-closing O-benzylation
      reaction, has been developed to overcome the problems associated to
      regioselective benzylation reactions. The strategy has been applied to the high
      yielding synthesis of the pyrrolidine glycosidase inhibitors DMDP and DGDP.

PMID- 16408900
TI  - Fluorous mixture synthesis of (-)-dictyostatin and three stereoisomers.
AB  - [reaction: see text] A mixture of four stereoisomers whose configurations are
      encoded by fluorous silyl protecting groups has been prepared and converted over
      22 steps to a mixture of protected dictyostatins. Demixing by fluorous HPLC
      followed by removal of the fluorous protecting groups (detagging) provides
      dictyostatin and three C6,C7 stereoisomers. Biological evaluation showed that the
      monoepimers of the natural product retained highly potent activity.

PMID- 16408901
TI  - Noncryogenic I/Br-Mg exchange of aromatic halides bearing sensitive functional
      groups using i-PrMgCl-bis[2-(N,N-dimethylamino)ethyl] ether complexes.
AB  - [reaction: see text] Iodo- and bromoaromatics bearing sensitive carboxylic ester
      and cyano groups underwent a selective halide-magnesium exchange with
      isopropylmagnesium chloride at ambient temperature in the presence of bis[2-(N,N
      dimethylamino)ethyl] ether to afford the corresponding Grignard reagents. The
      newly formed reactive Grignard reagents were allowed to react with electrophiles
      such as trimethylborate to afford arylboronic acids in good to excellent yields.

PMID- 16408902
TI  - New zirconium-mediated approach toward regio- and stereocontrolled synthesis of
      trans-enediynes.
AB  - [reaction: see text] The coupling reactions of alpha-alkynylated
      zirconacyclopentene based on 1,4-bis(trimethylsilyl)-1,3-butadiyne with
      unsaturated compounds are described, which provide an efficient, regio- and
      stereocontrollable synthesis of trans-enediynes in a one-pot procedure. An
      interesting alkynyl group shift from alpha- to beta-position of the zirconium
      center during the reaction was observed, which was accountable for the novel
      transformations to trans-enediynes.

PMID- 16408903
TI  - Mercuric chloride and iodide mediated cyclization of tethered alkynedithioacetals
      as a general route to five- and six-membered rings: tuning of regioselectivity by
      alkyne substitution.
AB  - [reaction: see text] Mercuric chloride mediated cyclization of tethered
      alkynedithioacetals has been established as a general route to five- and six
      membered carbocycles and heterocycles. Substitution at the alkyne terminus leads
      to preferential formation of five-membered rings, whereas unsubstituted
      alkynedithioacetals give six-membered rings as the major products. Mercuric
      iodide interrupts the reaction at the intermediate dithioacetal stage.

PMID- 16408904
TI  - Divergent cycloaddition and ring-closing metathesis approaches to indolizidine
      and pyrrolo[1,2-a]azepine skeletons from a chiral precursor: an expeditious route
      to (-)-8-epi-swainsonine triacetate.
AB  - [reaction: see text] A divergent strategy for the synthesis of diverse
      azabicyclic ring systems has been developed in which a chiral N-allylpyrrolidine
      derivative, obtained from a carbohydrate precursor was converted to (-)-8-epi
      swainsonine triacetate by RCM and to a pyrrolo[1,2-a]azepine derivative and a 3
      hydroxymethyl-substituted indolizidine by N-allylcarbohydrate nitrone and nitrile
      oxide cycloadditions.

PMID- 16408906
TI  - Gold(III) porphyrin-catalyzed cycloisomerization of allenones.
AB  - [reaction: see text] Gold(III) porphyrin-catalyzed cycloisomerization of
      allenones gave the corresponding furans in good to excellent yields (up to 98%)
      and with quantitative substrate conversions. By recovering the Au(III) catalyst,
      a recyclable catalytic system is developed with over 8300 product turnovers
      attained for the cycloisomerization of 1-phenyl-buta-2,3-dien-1-one. The
      versatility of the gold(III) porphyrin catalyst was exemplified by its
      application to the hydroamination and hydration of phenylacetylene in 73% and 87%
      yield, respectively.

PMID- 16408905
TI  - Liphagal, a Selective inhibitor of PI3 kinase alpha isolated from the sponge
      akacoralliphaga: structure elucidation and biomimetic synthesis.
AB  - [structure: see text] Liphagal (1), a selective inhibitor of PI3K alpha, has been
      isolated from the marine sponge Aka coralliphaga collected in Dominica. The
      "liphagane" meroterpenoid carbon skeleton of liphagal (1) is new. A biomimetic
      total synthesis has been used to confirm the constitution of liphagal (1) and
      support a proposed biogenesis.

PMID- 16408907
TI  - Solid-phase approach to tetrahydroquinolones using a sulfur linker cleaved by
      SmI2.
AB  - [reaction: see text] A sulfur alpha-heteroatom-substituted carbonyl (HASC) linker
      has been utilized in a solid-phase approach to tetrahydroquinolones. The route
      illustrates the compatibility of the linker system with palladium-catalyzed
      transformations and its utility for library synthesis. The linker is cleaved by
      electron transfer from samarium(II) iodide.

PMID- 16408908
TI  - Oxidized bis(indolyl)methane: a simple and efficient chromogenic-sensing molecule
      based on the proton transfer signaling mode.
AB  - [reaction: see text] Oxidized bis(indolyl)methane, 1, a simple chromophore
      containing an acidic H-bond donor moiety and a basic H-bond acceptor moiety, can
      act as a selective colorimetric sensor either for F(-) in aprotic solvent or for
      HSO(4)(-) and weak acidic species in water-containing medium. The
      deprotonation/protonation of oxidized bis(indolyl)methane 1 is responsible for
      the dramatic color change.

PMID- 16408909
TI  - Improved method for the iodine(III)-mediated preparation of aryl sulfonimidates.
AB  - [reaction: see text] One-pot hypervalent iodine-mediated oxidations of
      arylsulfinamides to arylsulfonimidates is reported. Contrary to the case of
      alkylsulfinamides, use of iodosobenzene was not satisfactory. The reaction worked
      best with diacetoxyiodosobenzene (DIB) and a mild base (MgO). The influence of
      substituents on the iodine(III) reagent arene has been examined.

PMID- 16408910
TI  - High performance of a chiral diene-rhodium catalyst for the asymmetric 1,4
      addition of arylboroxines to alpha,beta-unsaturated ketones.
AB  - [reaction: see text] A rhodium complex coordinated with (S,S)-2,5
      dibenzylbicyclo[2.2.2]octa-2,5-diene (Bn-bod) showed high catalytic activity and
      high enantioselectivity in the asymmetric 1,4-addition of arylboroxines to cyclic
      alpha,beta-unsaturated ketones, 0.005-0.01 mol % of the catalyst giving high
      yields of the addition products with not lower than 94% ee. The turnover
      frequency of the catalyst is up to 1.4 x 10(4) h(-1).

PMID- 16408911
TI  - Expedient synthesis of (+/-)-bipinnatin J.
AB  - [reaction: see text] A nine-step, stereoselective synthesis of bipinnatin J is
      described, which features a ruthenium-catalyzed Alder-ene reaction, a Stille
      cross coupling, and an intramolecular Nozaki-Hiyama-Kishi allylation as key
      steps. The biosynthetic relationship between bipinnatin J and complex polycyclic
      diterpenes isolated from gorgonian corals is discussed.

PMID- 16408912
TI  - Synthesis of enantiopure allylamines by reductive alkylation of amino epoxides
      with organolithium reagents.
AB  - [reaction: see text] Transformation of enantiopure (2R,1'S)-2-(1
      aminoalkyl)epoxides 1 into the corresponding allylamines 2 is described. The
      opening of the epoxide ring with different organolithium compounds takes place
      with total selectivity and in high yields.

PMID- 16408915
TI  - Statistical heterospectroscopy, an approach to the integrated analysis of NMR and
      UPLC-MS data sets: application in metabonomic toxicology studies.
AB  - Statistical heterospectroscopy (SHY) is a new statistical paradigm for the
      coanalysis of multispectroscopic data sets acquired on multiple samples. This
      method operates through the analysis of the intrinsic covariance between signal
      intensities in the same and related molecules measured by different techniques
      across cohorts of samples. The potential of SHY is illustrated using both 600-MHz
      1H NMR and UPLC-TOFMS data obtained from control rat urine samples (n = 54) and
      from a corresponding hydrazine-treated group (n = 58). We show that direct cross
      correlation of spectral parameters, viz. chemical shifts from NMR and m/z data
      from MS, is readily achievable for a variety of metabolites, which leads to
      improved efficiency of molecular biomarker identification. In addition to
      structure, higher level biological information can be obtained on metabolic
      pathway activity and connectivities by examination of different levels of the NMR
      to MS correlation and anticorrelation matrixes. The SHY approach is of general
      applicability to complex mixture analysis, if two or more independent
      spectroscopic data sets are available for any sample cohort. Biological
      applications of SHY as demonstrated here show promise as a new systems biology
      tool for biomarker recovery.

PMID- 16408916
TI  - Selective ion filtering by digital thresholding: a method to unwind complex ESI
      mass spectra and eliminate signals from low molecular weight chemical noise.
AB  - In this work, we present a simple method by which to preferentially detect either
      high molecular weight or low molecular weight ions generated by electrospray
      ionization. This approach, termed selective ion filtering by digital thresholding
      (SIFdT) is demonstrated on a commercial ESI-TOF instrument that employs a fast
      digitizer coupled to a microchannel plate detector. The digital representation of
      each individual scan is digitally filtered prior to spectral coaddition. As
      larger, more highly charged ions induce a more intense response than low
      molecular weight singly charged species, a digital threshold can be set that
      precludes the detection of singly charged species yet permits the efficient
      detection of larger, more highly charged species. In this work, we demonstrate
      the applicability of this approach to eliminate low molecular weight chemical
      noise in ESI-TOF spectra of oligonucleotide and protein ions, demonstrate
      improved dynamic range for analyte solutions containing high levels of low MW
      constituents, and show that spectra acquired at different digital thresholds can
      be subtracted to yield spectra of low molecular weight constituents with improved
      mass measurement accuracies. A notional scheme is presented in which an
      alternative digitization approach is employed using multiple differentially
      thresholded data streams to allow improved internal mass calibration and higher
      resolution ion partitioning.

PMID- 16408917
TI  - Nanoparticle conjugation increases protein partitioning in aqueous two-phase
      systems.
AB  - We describe the effect of bioconjugation to colloidal Au nanoparticles on protein
      partitioning in poly(ethylene glycol) (PEG)/dextran aqueous two-phase systems
      (ATPS). Horseradish peroxidase (HRP) was conjugated to colloidal Au nanoparticles
      by direct adsorption. Although HRP alone had very little phase preference, HRP/Au
      nanoparticle conjugates typically partitioned to the PEG-rich phase, up to a
      factor of 150:1 for conjugates of 15-nm colloidal Au. Other protein/Au
      nanoparticle conjugates exhibited partitioning of greater than 2000:1 to the
      dextran-rich phase, as compared with approximately 5:1 for the free protein. The
      degree of partitioning was dependent on polymer concentration and molecular
      weight, nanoparticle diameter, and in some instances, nanoparticle concentration
      in the ATPS. The substantial improvements in protein partitioning achievable by
      conjugation to Au nanoparticles appear to result largely from increased surface
      area of the conjugates and require neither chemical modification of the proteins
      or polymers with affinity ligands, increased polymer concentrations, nor addition
      of high concentrations of salts. Adsorption to colloidal particles thus provides
      an attractive route for increased partitioning of enzymes and other proteins in
      ATPS. Furthermore, these results point to ATPS partitioning as a powerful means
      of purification for biomolecule/nanoparticle conjugates, which are increasingly
      used in diagnostics and materials applications.

PMID- 16408918
TI  - Hydrodynamic dispersion in shallow microchannels: the effect of cross-sectional
      shape.
AB  - We highlight the fact that hydrodynamic dispersion in shallow microchannels is in
      most cases controlled by the width of the cross section rather than by the much
      thinner height of the channel. We identify the relevant time scales that separate
      the various regimes involved. Using the lubrication approximation, we provide
      simple formulas that permit a quantitative evaluation of dispersion for most
      shallow cross-sectional shapes in the "long-time" Taylor regime, which is
      effectively diffusive. Because of its relevance for microfluidic systems, we also
      provide results for the short-time "ballistic regime" (for specific initial
      conditions). The special cases of parabolic and quasi-rectangular shapes are
      considered due to their frequent use in microsystems.

PMID- 16408919
TI  - Third-generation biosensor for lactose based on newly discovered cellobiose
      dehydrogenase.
AB  - The present paper describes the principle and characteristics of a biosensor for
      lactose based on a third-generation design involving cellobiose dehydrogenase. As
      resulted from a previous comparative study (submitted manuscript), the novelty of
      this lactose biosensor is based on highly efficient direct electron transfer
      between two newly discovered cellobiose dehydrogenases (CDH), from the white rot
      fungi Trametes villosa and Phanerochaete sordida, and a solid spectrographic
      graphite electrode. CDH was immobilized on the electrode surface (0.073 cm2) by
      simple physical adsorption, and the CDH-modified electrode was next inserted into
      a wall-jet amperometric cell connected on-line to a flow injection setup (0.5 mL
      x min(-1)). The P. sordida CDH-based lactose biosensor, proved to be the better
      one, has a detection limit for lactose of 1 microM, a sensitivity of 1100 microA
      x mM(-1) x cm(-2), a response time of 4 s (the time required to obtain the
      maximum peak current), and a linear range from 1 to 100 microM lactose
      (correlation coefficient 0.998). The simplicity of construction and analytical
      characteristics make this CDH-based lactose biosensor an excellent alternative to
      previous lactose biosensors reported in the literature or commercially available.
      The CDH-lactose sensor was used to quantify the content of lactose in pasteurized
      milk, buttermilk, and low-lactose milk, using the standard addition method. No
      effects of the samples matrixes were observed. The operational stability of the
      sensor was tested for 11 h by continuous injection of 100 microM lactose (290
      injections). The final signal of the sensor was maintained at 98% of its initial
      signal, with a low standard deviation of 1.72 (RSD 2.41%).

PMID- 16408920
TI  - Structure and thickness dependence of "molecular wiring" in nanostructured enzyme
      multilayers.
AB  - Supramolecular organized multilayers composed of glucose oxidase (GOx) and osmium
      derivatized poly(allylamine) redox polymer have been self-assembled
      electrostatically from Os-polyelectrolyte solutions of variable pH (5.5-8.8)
      leading to a decrease of the linear charge density in the PAH-Os with increasing
      pH. The layer-by-layer enzyme multilayers were studied by ellipsometry, quartz
      crystal microbalance, AFM, cyclic voltammetry, and electrocatalytic oxidation of
      beta-D-glucose. At higher adsorption solution pH, an increase in the film
      thickness, enzyme loading, and redox charge was observed. While the
      electrocatalytic response increases with the increase of the adsorption solution
      pH (decrease of the polyelectrolyte linear charge), the FADH2 oxidation
      bimolecular rate constant has a maximum in the pH range 7.0-7.5 where a change in
      the film growth mechanism is observed.

PMID- 16408921
TI  - Improving the linearity of infrared diffuse reflection spectroscopy data for
      quantitative analysis: an application in quantifying organophosphorus
      contamination in soil.
AB  - Diffuse reflection data are presented for ethyl methylphosphonate in a fine Utah
      dirt sample as a model system for organophosphate-contaminated soil. The data
      revealed a chemometric artifact when the spectra were represented in Kubelka-Munk
      units that manifests as a linear dependence of spectral peak height on variations
      in the observed baseline position (i.e., the position of the observed
      transmission intensity where no absorption features occur in the sample
      spectrum). We believe that this artifact is the result of the mathematical
      process by which the raw data are converted into Kubelka-Munk units, and we
      developed a numerical strategy for compensating for the observed effect and
      restoring chemometric precision to the diffuse reflection data for quantitative
      analysis while retaining the benefits of linear calibration afforded by the
      Kubelka-Munk approach. We validated our Kubelka-Munk correction strategy by
      repeating the experiment using a simpler system--pure caffeine in potassium
      bromide. The numerical preprocessing includes conventional multiplicative scatter
      correction coupled with a baseline offset correction that facilitates the use of
      quantitative diffuse reflection data in the Kubelka-Munk formalism for the
      quantitation of contaminants in a complex soil matrix, but is also applicable to
      more fundamental diffuse reflection quantitative analysis experiments.

PMID- 16408922
TI  - Voltammetric behavior of nitrazepam and its determination in serum using liquid
      chromatography with redox mode dual-electrode detection.
AB  - A method involving high-performance liquid chromatography with dual-electrode
      electrochemical detection in the redox mode (LC-DED) has been successfully
      developed for the determination of the benzodiazepine tranquilizer, nitrazepam,
      in serum. To elucidate the electrochemical mechanism occurring at a glassy carbon
      electrode, cyclic voltammetry was preformed with 1 mM solutions of nitrazepam at
      pH values between 2 and 12, using a potential range from -1.5 to +1.5 V. Two
      reduction peaks were observed over the whole pH range; the first, designated R1,
      was consistent with the 4e-, 4H+ reduction of the 7-nitro group to a
      hydroxylamine species; the second more negative peak, designated R2, was shown to
      be the result of a 2e-, 2H+ reduction of the 4-5 azomethine group. On the reverse
      anodic scan, an oxidation signal was observed, designated O1, which was
      considered to result from a 2e-, 2H+ oxidation of the hydroxylamine to a nitroso
      group. On the second forward scan, a new reduction peak, designated R3, was
      observed, which was considered to result from reduction of the nitroso species
      back to the hydroxylamine species. Studies were then undertaken to exploit the
      hydroxylamine/nitroso redox couple using LC-DED detection for the measurement of
      nitrazepam in serum. The optimal chromatographic conditions were found to
      comprise a mobile phase containing 60% methanol, 40% 50 mM pH 4.1 acetate buffer,
      in conjunction with a Hypersil C18 250 mm x 4.6 mm column. Hydrodynamic
      voltammetric studies were undertaken to optimize the operating potentials
      required for dual-electrode detection. It was found that an applied potential of 
      2.4 V was optimum for the "generator" cell and +0.5 V for the "detector" cell.
      The proposed method was evaluated by carrying out replicate nitrazepam
      determinations on spiked bovine and human serum samples. The former evaluation
      was preformed at a concentration of 11.2 microg mL(-1), and the latter at 1670 ng
      mL(-1). For bovine serum, the recovery of nitrazepam was found to be 75.8% and
      the associated coefficient of variation was 6.1% (n = 6). For human serum, the
      recovery was 74.1% with a coefficient of variation of 7.8% (n = 7). These data
      suggest that the method holds promise for applications in toxicology and where an
      alternative reliable method to confirm drug abuse may be required.

PMID- 16408923
TI  - Urine testing for designer steroids by liquid chromatography with androgen
      bioassay detection and electrospray quadrupole time-of-flight mass spectrometry
      identification.
AB  - New anabolic steroids show up occasionally in sports doping and in veterinary
      control. The discovery of these designer steroids is facilitated by findings of
      illicit preparations, thus allowing bioactivity testing, structure elucidation
      using NMR and mass spectrometry, and final incorporation in urine testing.
      However, as long as these preparations remain undiscovered, new designer steroids
      are not screened for in routine sports doping or veterinary control urine tests
      since the established GC/MS and LC/MS/MS methods are set up for the monitoring of
      a few selected ions or MS/MS transitions of known substances only. In this study,
      the feasibility of androgen bioactivity testing and mass spectrometric
      identification is being investigated for trace analysis of designer steroids in
      urine. Following enzymatic deconjugation and a generic solid-phase extraction,
      the samples are analyzed by gradient LC with effluent splitting toward two
      identical 96-well fraction collectors. One well plate is used for androgen
      bioactivity detection using a novel robust yeast reporter gene bioassay yielding
      a biogram featuring a 20-s time resolution. The bioactive wells direct the
      identification efforts to the corresponding well numbers in the duplicate plate.
      These are subjected to high-resolution LC using a short column packed with 1.7
      microm C18 material and coupled with electrospray quadrupole time-of-flight mass
      spectrometry (LC/QTOFMS) with accurate mass measurement. Element compositions are
      calculated and used to interrogate electronic substance databases. The
      feasibility of this approach for doping control is demonstrated via the screening
      of human urine samples spiked with the designer anabolic steroid
      tetrahydrogestrinone. Application of the proposed methodology, complementary to
      the established targeted urine screening for known anabolics, will increase the
      chance of finding unknown emerging designer steroids, rather then being solely
      dependent on findings of the illicit preparations themselves.

PMID- 16408924
TI  - PepHMM: a hidden Markov model based scoring function for mass spectrometry
      database search.
AB  - An accurate scoring function for database search is crucial for peptide
      identification using tandem mass spectrometry. Although many mathematical models
      have been proposed to score peptides against tandem mass spectra, our method
      (called PepHMM, http://msms.cmb.usc.edu) is unique in that it combines
      information on machine accuracy, mass peak intensity, and correlation among ions
      into a hidden Markov model (HMM). In addition, we develop a method to calculate
      statistical significance of the HMM scores. We implement the method and test them
      on two sets of experimental data generated by two different types of mass
      spectrometers and compare the results with MASCOT and SEQUEST under the same
      condition. One experimental results show that PepHMM has a much higher accuracy
      (with 6.5% error rate) than MASCOT (with 17.4% error rate), and the other
      experimental results show that PepHMM identifies 43 and 31% more correct spectra
      than SEQUEST and MASCOT, respectively.

PMID- 16408925
TI  - Method for lipoprotein(a) density profiling by BiEDTA differential density
      lipoprotein ultracentrifugation.
AB  - In this article, we demonstrate the analytical power of linking density gradient
      ultracentrifugation with affinity separations. Here we address some of the
      analytical challenges in the study of lipoprotein(a), (Lp(a)). The mean density
      distribution of Lp(a) was determined by a differential density lipoprotein
      profile (DDLP). For DDLP, the lipoprotein density distribution of a serum sample
      with elevated Lp(a) levels was determined by ultracentrifugation using a BiEDTA
      complex as a density gradient. Lp(a) was removed from a second aliquot of the
      same serum sample by carbohydrate affinity using wheat germ agglutinin (WGA). WGA
      was demonstrated to have high specificity for Lp(a) in a serum sample. This
      sample was ultracentrifuged to obtain a lipoprotein density distribution in the
      absence of Lp(a). A DDLP was obtained after subtracting the Lp(a)-depleted
      lipoprotein density profile from the untreated lipoprotein density profile. The
      DDLP methodology reported herein gives relevant information of the lipoproteins
      in serum such as density, isoform, and subclass characteristics. Lp(a) was
      quantitatively isolated from serum with a recovery efficiency of 82%. Lp(a) was
      purified by ultracentrifugation. Lp(a) retained its inherent density (1.086 g/mL)
      and immunoreactivity. The major outcome of this research was the effectiveness of
      using affinity separations coupled with density ultracentrifugation for the
      isolation of pure Lp(a) from serum and its isoform characterization based on
      density by DDLP.

PMID- 16408926
TI  - Pushing the limits of mercury sensors with gold nanorods.
AB  - The method presented here provides a direct way to determine mercury in tap water
      samples at the parts-per-trillion level. Its outstanding selectivity and
      sensitivity results from the well-known amalgamation process that occurs between
      mercury and gold. The entire procedure takes less than 10 min. No sample
      separation or sample preconcentration is required. The only step prior to mercury
      determination consists of mixing the water sample with a gold nanorod solution in
      sodium borohydride. The analytical figures of merit demonstrate precise and
      accurate analysis at the parts-per-trillion level. The limit of detection (6.6 x
      10(-13) g x L(-1)) shows excellent potential for monitoring ultralow levels of
      mercury in water samples.

PMID- 16408927
TI  - Global identification of O-GlcNAc-modified proteins.
AB  - The O-linked N-acetylglucosamine (O-GlcNAc) modification of serine/threonine
      residues is an abundant posttranslational modification present in cytosolic and
      nuclear proteins. The functions and subproteome of O-GlcNAc modification remain
      largely undefined. Here we report the application of the tagging-via-substrate
      (TAS) approach for global identification of O-GlcNAc-modified proteins. The TAS
      method utilizes an O-GlcNAc azide analogue for metabolic labeling of O-GlcNAc
      modified proteins, which can be chemoselectively conjugated for detection and
      enrichment of the proteins for proteomics studies. Our study led to the
      identification of 199 putative O-GlcNAc-modified proteins from HeLa cells, among
      which 23 were confirmed using reciprocal immunoprecipitation. Functional
      classification shows that proteins with diverse functions are modified by O
      GlcNAc, implying that O-GlcNAc might be involved in the regulation of multiple
      cellular pathways.

PMID- 16408928
TI  - Synthesis of a polyelectrolyte and its applications in laser
      desorption/ionization.
AB  - A novel laser energy-absorbing polymer derivatized from an energy-absorbing
      molecule has been synthesized. This polymer effectively eliminates the matrix
      addition step and the use of requisite small organic chemical matrixes from
      MALDI. The resulting polyelectrolyte-assisted laser desorption/ionization method
      has been proven to have some exceptional advantages over current MALDI methods.
      First, the matrix addition step from the LDI analytical process was eliminated.
      Second, the low molecular weight signal from energy-absorbing molecules was
      minimized by covalently linking the energy-absorbing molecules to the backbone of
      the polymer and other ionization-enhancing pendant groups on the backbone.
      Finally, the mass resolution of LDI was enhanced by minimizing chemical
      background noise throughout the spectrum. Polymeric linkage of energy-absorbing
      molecules aligns them with each other in an ordered structure, similar to MALDI
      matrix crystallization. Using the designed polymer film, laser
      desorption/ionization for proteins and peptides were successfully performed
      without the addition of any matrix. Analytical results for the synthesized
      monomer and polymers will be also presented.

PMID- 16408929
TI  - PNA-DNA hybridization study using labeled streptavidin by voltammetry and surface
      plasmon fluorescence spectroscopy.
AB  - Using ferrocene-streptavidin conjugates as amplifiers, we recently have
      demonstrated the simultaneous detection of DNA hybridization to peptide nucleic
      acid (PNA)-modified gold surfaces at the femtomole level by electrochemical and
      surface plasmon resonance techniques (Liu, J.; Tian, S.; Tiefenauer, L.; Nielsen,
      P. E.; Knoll, W. Anal. Chem. 2005, 77, 2756-2761). In this paper, a detailed
      study of the binding behavior of PNA-DNA is presented by square wave voltammetry
      and surface plasmon field-enhanced fluorescence spectroscopy (SPFS). The
      different binding constants for fully matched and single-mismatched DNA were
      obtained. The effect of the buffer concentration on the PNA-DNA hybrids was
      investigated using labeled streptavidin by cyclic voltammetry (CV) and SPFS. At
      high ionic strength, both the CV and SPFS signals were restrained dramatically,
      which is most probably due to a conformational change of the short-strand PNA-DNA
      helices on the surface. We conclude that the combination of electrochemical
      techniques with SPFS is very useful for the study of short DNA structure
      transformation.

PMID- 16408930
TI  - Steady-state voltammetric response of the nanopore electrode.
AB  - The steady-state voltammetric response of the truncated conical-shaped glass
      nanopore electrode is presented. Analytical theory, finite-element simulations,
      and experimental measurement of the diffusive flux of a redox molecule through
      the pore orifice demonstrate that the steady-state current decreases rapidly as
      the pore depth increases and then asymptotically approaches a constant value when
      the pore depth is approximately 50x larger than the pore orifice. The asymptotic
      limit of the steady-state current is only a function of the pore orifice radius
      and the cone angle of the pore and has a finite value for all cone angles greater
      than zero. Experimental confirmation of the predicted dependence on pore depth is
      obtained using nanopore electrodes with 100-1000 nm orifice radii, by measuring
      the steady-state voltammetric current corresponding to the oxidation of ferrocene
      in acetonitrile solutions containing an excess of supporting electrolyte.

PMID- 16408931
TI  - Instrumentation for multidimensional luminescence spectroscopy and its
      application to low-temperature analysis in Shpol'skii matrixes and optically
      scattering media.
AB  - We present a single instrument with the capability to collect multidimensional
      data formats in both the fluorescence and the phosphorescence time domains. We
      also demonstrate the ability to perform luminescence measurements in highly
      scattering media by comparing the precision of measurements in Shpol'skii
      solvents to those obtained in "snowlike" matrixes and solid samples. For decades,
      conventional low-temperature methodology has been restricted to optically
      transparent media. This restriction has limited its application to organic
      solvents that freeze into a glass. We remove this limitation with the use of
      cryogenic fiber-optic probes.

PMID- 16408932
TI  - Performance of a linear ion trap-Orbitrap hybrid for peptide analysis.
AB  - Proteomic analysis of digested complex protein mixtures has become a useful
      strategy to identify proteins involved in biological processes. We have evaluated
      the use of a new mass spectrometer that combines a linear ion trap and an
      Orbitrap to create a hybrid tandem mass spectrometer. A digested
      submandibular/sublingual saliva sample was used for the analysis. We find the
      instrument is capable of mass resolution in excess of 40,000 and mass measurement
      accuracies of less than 2 ppm for the analysis of complex peptide mixtures. Such
      high mass accuracy allowed the elimination of virtually any false positive
      peptide identifications, suggesting that peptides that do not match the
      specificity of the protease used in the digestion of the sample should not
      automatically be considered as false positives. Tandem mass spectra from the
      linear ion trap and from the Orbitrap have very similar ion abundance ratios. We
      conclude this instrument will be well suited for shotgun proteomic types of
      analyses.

PMID- 16408933
TI  - Identification of microcystin toxins from a strain of Microcystis aeruginosa by
      liquid chromatography introduction into a hybrid linear ion trap-Fourier
      transform ion cyclotron resonance mass spectrometer.
AB  - The cyclic heptapeptide microcystin toxins produced by a strain of Microcystis
      aeruginosa that has not been investigated previously were separated by liquid
      chromatography and identified by high-accuracy m/z measurements of their [M + H]+
      ions and the fragment ions produced by collision-activated dissociation of the [M
      + H]+ ions. The cyanobacteria B2666 strain was cultured in a standard growth
      medium, and the toxins were released from the cells, extracted from the aqueous
      phase, and concentrated using standard procedures. The microcystins were
      separated by reversed-phase microbore liquid chromatography and introduced
      directly into a hybrid linear ion trap-Fourier transform ion cyclotron resonance
      mass spectrometer with electrospray ionization. The known microcystins (MC) MC
      LR, MC-LA, [MeSer7]MC-LR, MC-LL, MC-LF, and MC-L(Aba) were identified along with
      the two previously unreported structural variants [Asp3]MC-LA and [Asp3]MC-LL. In
      addition to the [M + H]+ ions, accurate m/z measurements were made of 12-18
      product ions for each identified microcystin. The mean difference between
      measured and calculated exact m/z was less than 2 parts per million, which often
      allowed assignment of unique compositions to the observed ions. A mechanism is
      presented that accounts for an important collision-activated dissociation process
      that gives valuable sequence ions from microcystins that do not contain arginine.
      The analytical technique used in this work is capable of supporting fairly rapid
      and very reliable identifications of known microcystins when standards are not
      available and of most structural variants independent of additional information
      from other analytical techniques.

PMID- 16408934
TI  - Multiple and simultaneous fluorophore detection using fluorescence spectrometry
      and partial least-squares regression with sample-specific confidence intervals.
AB  - Fluorescent labeling is widely used in biological and chemical analysis, and the
      drive for increased throughput is stretching multiplexing capabilities to the
      limit. The limiting factor in multiplexed analyses is the ability to subsequently
      deconvolute the signals. Consequently, alternative approaches for interpreting
      complex data sets are required to allow individual components to be identified.
      Here we have investigated the application of a novel approach to multiplexed
      analysis that does not rely on multivariate curve resolution to achieve signal
      deconvolution. The approach calculates a sample-specific confidence interval for
      a multivariate (partial least-squares regression (PLSR)) prediction, thereby
      enabling the estimation of the presence or absence of each fluorophore based on
      the total spectral signal. This approach could potentially be applied to any
      multiplexed measurement system and has the advantage over the current algorithm
      based methods that the requirement for resolution of spectral peaks is not
      central to the method. Here, PLSR was used to obtain the concentrations for up to
      eight dye-labeled oligonucleotides at levels of (0.6-5.3) x 10(-6) M. The sample
      specific prediction intervals show good discrimination for the presence/absence
      of seven of the eight labeled oligonucleotides with efficiencies ranging from
      approximately 91 to 100%.

PMID- 16408935
TI  - Decyl methacrylate-based microspot optodes.
AB  - Optode sensing membranes employing decyl methacrylate cross-linked with 1,6
      hexanediol dimethacrylate as the polymer support were fabricated by a direct
      microspotting method on several surfaces. Photopolymerization was used to attach
      the microspots to the substrate. Using this method, diameters in the micrometer
      domain were obtained. Silanized glass, poly(methyl methacrylate) (PMMA),
      polycarbonate, and poly(dimethylsiloxane) were tested as possible substrates.
      Both polypropylene tips and the steel tips of drafting pens were used for
      spotting. It was determined that both silanized glass and PMMA gave working
      optodes, but the ones on PMMA did not fit the theoretical model. Diameters of 994
      +/- 80 and 1279 +/- 85 microm were obtained on silanized glass and PMMA,
      respectively, using the polypropylene tips for spotting. Different size optodes
      were fabricated using 0.35- and 0.50-mm steel drafting pen tips. The 0.35-mm tips
      produced diameters of 895 +/- 26 and 688 +/- 54 microm on silanized glass and
      PMMA, respectively, and the 0.50-mm tips produced diameters of 1274 +/- 94 microm
      on silanized glass and 839 +/- 28 microm on PMMA. Thus, the microspot size can be
      controlled based on the hydrophobicity of the surface and the size of the tip
      used for spotting. Calibration plots of potassium optode microspots indicated
      that miniaturization does not alter response characteristics, such as
      selectivity, response time, and dynamic range, of the optodes.

PMID- 16408936
TI  - Comprehensive study of bioanalytical platforms: xanthine oxidase.
AB  - A comprehensive study of a general bioanalytical platform for biosensor
      applications is presented using xanthine oxidase (XnOx) as a case study within
      the framework of developing approaches of broad applicability. In this context,
      emphasis is placed on amperometric biosensors based on XnOx, which has been
      immobilized by covalent binding to gold electrodes modified with dithiobis-N
      succinimidyl propionate. The immobilized XnOx layers have been characterized
      using atomic force microscopy under liquid conditions and quartz crystal
      microbalance techniques. In addition, spatially resolved mapping of enzymatic
      activity has been carried out using scanning electrochemical microscopy. Redox
      dyes of phenothiazine derivatives, specifically, thionine and methylene blue,
      have been found to work well as electron acceptors for reduced XnOx. The kinetic
      parameters and equilibrium constants of the mediated enzymatic oxidation of
      xanthine in the presence of the above-mentioned redox dyes have been calculated.
      The response of the enzymatic electrode to varying xanthine concentrations has
      been obtained in the presence of thionine or methylene blue as redox mediator in
      solution. Under these conditions, xanthine could be determined amperometrically
      at +0.2 V versus SSCE.

PMID- 16408937
TI  - High-resolution computer simulations of stacking of weak bases using a transient
      pH boundary in capillary electrophoresis. 1. Concept and impact of sample ionic
      strength.
AB  - The dynamics of focusing weak bases using a transient pH boundary was examined
      via high-resolution computer simulation software. Emphasis was placed on the
      mechanism and impact that the presence of salt, namely, NaCl, has on the ability
      to focus weak bases. A series of weak bases with mobilities ranging from 5 x 10(
      9) to 30 x 10(-9) m2/V x s and pKa values between 3.0 and 7.5 were examined using
      a combination of 65.6 mM formic acid, pH 2.85, for the separation electrolyte,
      and 65.6 mM formic acid, pH 8.60, for the sample matrix. Simulation data show
      that it is possible to focus weak bases with a pKa value similar to that of the
      separation electrolyte, but it is restricted to weak bases having an
      electrophoretic mobility of 20 x 10(-9) m2/V x s or quicker. This mobility range
      can be extended by the addition of NaCl, with 50 mM NaCl allowing stacking of
      weak bases down to a mobility of 15 x 10(-9) m2/V x s and 100 mM extending the
      range to 10 x 10(-9) m2/V x s. The addition of NaCl does not adversely influence
      focusing of more mobile bases, but does prolong the existence of the transient pH
      boundary. This allows analytes to migrate extensively through the capillary as a
      single focused band around the transient pH boundary until the boundary is
      dissipated. This reduces the length of capillary that is available for separation
      and, in extreme cases, causes multiple analytes to be detected as a single highly
      efficient peak.

PMID- 16408939
TI  - Intein-mediated reporter gene assay for detecting protein-protein interactions in
      living mammalian cells.
AB  - For nondestructive analysis of chemical processes in living mammalian cells, here
      we developed a new reporter gene assay for detecting cytosolic protein-protein
      interactions based on protein splicing of transcription factors with DnaE
      inteins. The protein splicing induces connection of a DNA-binding protein
      (modified LexA; mLexA) with a transcription activation domain of a herpes simplex
      virus protein (VP16AD). We thereby circumvented the limitation of earlier methods
      for monitoring protein-protein interactions, including the two-hybrid systems,
      protein complementation systems (PCS), and protein reconstitution systems, and
      rather combined their advantages. To test the applicability of this method, we
      monitored epidermal growth factor (EGF)-induced interactions on cell membranes of
      a known partner, an oncogenic product Ras and its target Raf-1. Ras was connected
      with N-terminal DnaE and mLexA, while Raf-1 was connected with C-terminal DnaE
      and VP16AD. Upon stimulation with EGF, the interaction between Ras and Raf-1
      triggered folding of the DnaEs, thereby inducing protein splicing to form mLexA
      VP16AD fusion protein, and transcription of a reporter gene, firefly luciferase.
      The extent of Ras-Raf-1 interaction was quantified by measuring the luciferase
      activity. The interaction was not able to be monitored by two-hybrid systems nor
      by PCS of split firefly luciferases; however, by using the protein splicing
      elements and the reporter gene, we obtained the bioluminescence signals
      sufficient for evaluation of the interactions close to cell membranes.

PMID- 16408938
TI  - Sterol binding assay using surface plasmon fluorescence spectroscopy.
AB  - We describe the design of a novel in vitro assay to study the interaction of
      soluble proteins with small hydrophobic sterol ligands. The sterol molecules are
      incorporated in an artificial membrane system in order to mimic their arrangement
      found in a biomembrane. The artificial membrane setup is monitored in real time
      by surface plasmon spectroscopy. Binding of fluorescently labeled soluble protein
      is observed by optical detection with surface plasmon enhanced fluorescence
      spectroscopy. By application of the novel assay, we demonstrate that four
      different oxidized sterol molecules are specifically recognized by the yeast
      protein Osh5p, a presumed oxysterol binding protein. Osh5p from yeast is the
      first oxysterol binding protein homologue for which oxysterol binding is shown
      with this new technique. With the design of our novel in vitro oxysterol binding
      assay, we have solved the technically challenging difficulty of presenting
      hydrophobic ligands to hydrophilic proteins in aqueous media.

PMID- 16408940
TI  - Investigation of the chromatographic process via pulsed-gradient spin-echo
      nuclear magnetic resonance. Role of the solvent composition in partitioning
      chromatography.
AB  - The diffusional properties of molecules in solution vary dramatically upon
      addition of a solid chromatographic phase. This effect can be monitored via
      pulsed-gradient spin-echo NMR used in conjunction with moderately fast rotation
      of the sample (high-resolution magic angle spinning) to produce exploitable
      spectra. The molecular diffusion coefficients observed in this condition are
      averages reflecting the equilibrium population distribution among the different
      phases. It is thus possible to use this information for investigating a crucial
      step of reversed-phase chromatography, namely, the partitioning of the analyte
      between different phases. In this work, we describe the evolution of the apparent
      diffusion coefficient of typical solutes for water/acetonitrile solvent mixtures
      of varying proportions.

PMID- 16408941
TI  - Large-scale human metabolomics studies: a strategy for data (pre-) processing and
      validation.
AB  - A large metabolomics study was performed on 600 plasma samples taken at four time
      points before and after a single intake of a high fat test meal by obese and lean
      subjects. All samples were analyzed by a liquid chromatography-mass spectrometry
      (LC-MS) lipidomic method for metabolic profiling. A pragmatic approach combining
      several well-established statistical methods was developed for processing this
      large data set in order to detect small differences in metabolic profiles in
      combination with a large biological variation. Such metabolomics studies require
      a careful analytical and statistical protocol. The strategy included data
      preprocessing, data analysis, and validation of statistical models. After several
      data preprocessing steps, partial least-squares discriminant analysis (PLS-DA)
      was used for finding biomarkers. To validate the found biomarkers statistically,
      the PLS-DA models were validated by means of a permutation test, biomarker
      models, and noninformative models. Univariate plots of potential biomarkers were
      used to obtain insight in up- or downregulation. The strategy proposed proved to
      be applicable for dealing with large-scale human metabolomics studies.

PMID- 16408942
TI  - Application of selected-ion flow tube mass spectrometry to the real-time
      detection of triacetone triperoxide.
AB  - A fast, efficient, real-time method for the quantitative analysis of the peroxide
      explosive, TATP, is described. The method utilizes rapid ion-molecule reactions
      of chemical reagent ions with the vapor above solid TATP. The reactions of three
      reagent ions (H3O+, O2+, NO+) were examined. Although all three ions exhibited a
      near-collision-rate reaction with TATP, only NO+ showed product ions that provide
      unequivocal evidence for a TATP-based explosive. The limit of detection of TATP
      in the gas phase is 10 ppb (4 x 10(-10) mol L(-1)).

PMID- 16408943
TI  - Interactions of bupivacaine with a molecularly imprinted polymer in a monolithic
      format studied by NMR.
AB  - A trimethylolpropane trimethacrylate-based monolith of dimensions carefully
      chosen to fit exactly in a standard 4-mm solid-state CP/MAS NMR rotor was
      photopolymerized and subsequently molecularly imprinted with bupivacaine using a
      grafting protocol with methacrylic acid and ethylene dimethacrylate as monomers.
      As no crushing or grinding of the monolith was necessary, additional unspecific
      surface area was not created. This procedure ascertains that differences observed
      between imprinted and nonimprinted polymers are due only to graft imprinted
      surfaces and give therefore better results in NMR spectroscopy due to less
      unspecific interactions between analyte and monolith. This improves the
      comparability to chromatographic evaluations where uncrushed monolithic columns
      are also used. To track interactions between analyte and stationary phase, the
      saturation transfer difference (STD) technique was applied on the polymer in the
      suspended state using the same solvent as in the chromatographic evaluation. This
      relatively new NMR method has to our knowledge not been used on chromatographic
      materials before. By using STD NMR on pristine monoliths, it was possible to
      measure large differences between the imprinted or nonimprinted polymers and the
      analyte indicating significant differences in the interaction mechanisms. These
      could be directly correlated with retention differences observed in
      chromatographic evaluations.

PMID- 16408944
TI  - Lipid profiling by multiple precursor and neutral loss scanning driven by the
      data-dependent acquisition.
AB  - Data-dependent acquisition of MS/MS spectra from lipid precursors enables to
      emulate the simultaneous acquisition of an unlimited number of precursor and
      neutral loss scans in a single analysis. This approach takes full advantage of
      rich fragment patterns in tandem mass spectra of lipids and enables their
      profiling by complex (Boolean) scans, in which masses of several fragment ions
      are considered within a single logical framework. No separation of lipids is
      required, and the accuracy of identification and quantification is not
      compromised, compared to conventional precursor and neutral loss scanning.

PMID- 16408945
TI  - Nanoscale glassification of gold substrates for surface plasmon resonance
      analysis of protein toxins with supported lipid membranes.
AB  - Surface plasmon resonance (SPR) spectroscopy, a powerful tool for biosensing and
      protein interaction analysis, is currently confined to gold substrates and the
      relevant surface chemistries involving dextran and functional thiols. Drawbacks
      of using self-assembled monolayers (SAMs) for SPR-related surface modification
      include limited stability, pinhole defects, bioincompatibility, and nonspecific
      protein adsorption. Here we report the development of stable nanometer-scale
      glass (silicate) layers on gold substrates for SPR analysis of protein toxins.
      The nanoscale silicate layers were built up with layer-by-layer deposition of
      poly(allylamine hydrochloride) and sodium silicate, followed by calcination at
      high temperature. The resulting silicate films have a thickness ranging from 2 to
      15 nm and demonstrate outstanding stability in flow cell conditions. The use of
      these surfaces as a platform to construct supported bilayer membranes (SBMs) is
      demonstrated, and improved performance against protein adsorption on SBM-coated
      surfaces is quantified by SPR measurements. SBMs can be formed reproducibly on
      the silicate surface via vesicle fusion and quantitatively removed using
      injection of 5% Triton X-100 solution, generating a fresh surface for each test.
      Membrane properties such as lateral diffusion of the SBMs on the silicate films
      are characterized with photobleaching methods. Studies of protein binding with
      biotin/avidin and ganglioside/cholera toxin systems show detection limits lower
      than 1 microg/mL (i.e., nanomolar range), and the response reproducibility is
      better than 7% RSD. The method reported here allows many assay techniques
      developed for glass surfaces to be transferred to label-free SPR analysis without
      the need for adaptation of protocols and time-consuming synthetic development of
      thiol-based materials and opens new avenues for developing novel bioanalytical
      technologies for protein analysis.

PMID- 16408946
TI  - Electron paramagnetic resonance spectroscopy studies of oxidative degradation of
      an active pharmaceutical ingredient and quantitative analysis of the organic
      radical intermediates using partial least-squares regression.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was used to study the radical
      species formed during the oxidation of an active pharmaceutical ingredient in the
      solid state. It was found that the extent of radical generation correlated to the
      formation of an oxidative degradation product. Multifrequency EPR and electron
      nuclear double resonance spectroscopy gave additional information on the identity
      of the organic radical species involved in the oxidation process, and a mechanism
      was proposed for the degradation, involving the formation of both carbon-centered
      and peroxy radicals. The multivariate analysis technique of partial least-squares
      (PLS) regression was then used to determine the extent of oxidation of the active
      pharmaceutical ingredient from the EPR spectra. The suitability of this approach
      was demonstrated from its application to a series of standards. The conventional
      approach for the quantitative analysis of EPR spectra is to measure the peak
      height or to perform double integration of the spectral region containing the
      signal of interest. Both of these methods have intrinsic errors associated with
      them, particularly for weak EPR signals with a poor signal-to-noise ratio or a
      sloping background response. The results obtained showed that greatly improved
      quantitation was obtained using the PLS regression approach.

PMID- 16408947
TI  - Gold-coated magnetic particles for solid-phase immunoassays: enhancing
      immobilized antibody binding efficiency and analytical performance.
AB  - The preparation and characterization of gold-coated magnetic particles are
      described for use as more efficient solid-phase materials in immunoassay
      development. A thin gold coating on commercial tosylated magnetic polystyrene
      particles (4.5 microm) is achieved via an electroless plating method involving
      initial reaction of the particles with Sn(II), followed by redox deposition of
      Ag0, that serves as a catalytic site for the subsequent reduction of Na3Au(SO3)2
      in the presence of formaldehyde to yield the adhered gold layer. Scanning
      electron microscopy, energy-dispersive X-ray analysis, and X-ray photoelectron
      spectroscopy indicate the presence of the desired Au0 outer layer. To
      characterize the improved yield of antibody binding sites on such gold-coated
      phases, the modified particles are reacted with the free thiols of Fab' fragments
      of an anti-alkaline phosphatase (ALP) antibody to orient all the antigenic
      binding sites in a favorable direction. After equilibration with ALP, the amount
      of ALP bound to the surface of such particles is nearly 2.5-fold greater than on
      non-gold-coated particles possessing the same amount of immobilized anti-ALP
      Fab', but oriented randomly on the surface. The new gold-coated magnetic
      particles are further used as a solid phase for developing a sandwich-type enzyme
      immunoassay to detect C-reactive protein (CRP) using horseradish peroxidase as
      the enzyme label. The gold-coated magnetic particles with anti-CRP monoclonal
      Fab' reagents provide assays with enhanced assay slope (1.8-fold), lower
      nonspecific adsorption, and a detection limit improvement of nearly 10-fold (0.14
      vs 1.9 ng/mL) compared to the same Fab' anti-CRP immobilized on the initial
      tosylated polystyrene magnetic particles. The improved assay performance is
      attributed to the more favorable binding orientation of the self-assembled
      monolayer of Fab' fragments on the gold-coated particles compared to the random
      orientation on the non-gold-coated surfaces.

PMID- 16408948
TI  - Electrochemical nanoneedle biosensor based on multiwall carbon nanotube.
AB  - We report the fabrication and analytical functions of a biosensor based on a
      nanoneedle consisting of a multiwall carbon nanotube attached to the end of an
      etched tungsten tip. The devised electrode is the smallest needle-type biosensor
      reported to date. The nanoneedles prepared in this work are 30 nm in diameter and
      2-3 microm in length. Dopamine and glutamate, which are physiologically important
      neurotransmitters, were successfully detected using these nanoneedles. Bare
      nanoneedles detected dopamine in the range from 100 to 1000 microM by
      differential pulse voltammetry, and enzyme-modified nanoneedles were able to
      respond to glutamate in the 100-500 microM range by potentiostatic amperometry.

PMID- 16408949
TI  - Photoelectrochemical oxidation of DNA by ruthenium tris(bipyridine) on a tin
      oxide nanoparticle electrode.
AB  - Selective photoelectrochemical oxidation of DNA was achieved by ruthenium
      tris(bipyridine) immobilized on a tin oxide nanoparticle electrode. The metal
      complex was covalently attached to a protein, avidin, which adsorbed strongly on
      the tin oxide electrode by electrostatic interaction. Upon irradiation with 473
      nm light, anodic photocurrent was generated in a blank electrolyte and was
      enhanced significantly after addition of poly(guanadylic acid) (poly-G) into the
      electrolyte. The current increased progressively with the nucleotide
      concentration, suggesting the enhancement effect was related to poly-G. The
      action spectrum indicates that the photocurrent was initiated by light absorption
      of the ruthenium compound immobilized on the electrode. Among the various
      polynucleotides examined, poly-G produced the largest photocurrent increase,
      followed by poly-A, single-stranded DNA, chemically damaged DNA, and double
      stranded DNA, whereas poly-C and poly-U showed little effect. The combined
      experimental data support the hypothesis that the photoexcited Ru2+ species
      injects an electron into the semiconductor and produces Ru3+, which is then
      reduced back to Ru2+ by guanine and adenine bases in DNA, resulting in the
      recycling of the metal complex and enhanced photocurrent. The
      photoelectrochemical reaction can be employed as a new method for the detection
      of DNA damage.

PMID- 16408950
TI  - Genotoxicity screening using biocatalyst/DNA films and capillary LC-MS/MS.
AB  - Detection of DNA adducts can serve as a basis for genotoxicty screening of new
      chemicals and drugs. We report here a simple, sensitive procedure for this
      purpose using films containing DNA and a biocatalyst to mimic the metabolic
      action of human liver cytochrome P450s. DNA adducts formed from an in-situ
      generated toxic metabolite (styrene oxide) were detected at subpicomole levels
      after neutral thermal hydrolysis of the DNA films and analysis with capillary
      liquid chromatography with on-line column preconcentration and MS/MS detection.
      An on-line column switching system allowed for increased sample loading volume
      and analyte preconcentration. This approach provides an estimate of the relative
      rate of DNA damage.

PMID- 16408951
TI  - Enantioselective synthesis of (-)-dihydrocodeinone: a short formal synthesis of (
      )-morphine.
AB  - [reaction: see text] The radical cyclization approach to the morphine alkaloids
      has been applied in an asymmetric synthesis of (-)-dihydrocodeinone. A chiral
      cyclohexenol (R-32), from the CBS reduction of the enone, is the source of
      chirality. The first key step, tandem closure in which stereochemistry is
      controlled by geometric constraints, (-)-15b --> (+)-16, was followed by an
      unprecedented reductive hydroamination, completing the synthesis of (-)
      dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.

PMID- 16408952
TI  - Synthesis, structures, and photoinduced electron transfer reaction in the 9,9'
      spirobifluorene-bridged bipolar systems.
AB  - [reaction: see text] A series of 9,9'-spirobifluorene-bridged bipolar compounds
      DnAm bearing various n:m ratios for triarylamine (D) versus 1,3,4-oxadiazole
      conjugated oligoaryl moiety (A) have been synthesized to investigate the
      corresponding photoinduced electron transfer (PET) property. The excitation
      behaviors were probed by steady-state absorption, emission, fluorescence
      solvatochromism, and femtosecond fluorescence up-conversion spectroscopy. The
      overall reaction dynamics can be rationalized by the rate of PET, in combination
      with solvent relaxation dynamics. It was found that the rate of PET is dependent
      on the anchored D/A ratio. The rate of D1A1 and D2A1 was resolved to be
      approximately 2.44 x 10(12) and 2.32 x 10(12) s(-)(1), respectively, while it is
      irresolvable in D1A2 and D2A2 (>6.6 x 10(12) s(-)(1)). In another approach, based
      on the comprehensive X-ray data, cyclic voltammetry, and absorption/emission
      spectra, the rate of photoinduced electron transfer was also qualitatively
      estimated. Fair comparisons were made between experimental and theoretical
      approaches to gain detailed insight into the PET for the titled systems.

PMID- 16408953
TI  - [13C,15N]2-Acetamido-2-deoxy-D-aldohexoses and their methyl glycosides: synthesis
      and NMR investigations of J-couplings involving 1H, 13C, and 15N.
AB  - [reaction: see text] A series of 2-amino-2-deoxy-D-[1-13C]aldohexoses and their
      methyl glycosides was prepared with use of a simplified cyanohydrin reduction
      route. Four d-aldopentosylamines (arabino, lyxo, ribo, xylo) were prepared from
      the corresponding D-aldopentoses by reaction with NH3(g) in MeOH solvent,
      isolated in solid form, and characterized by 13C and 1H NMR. Hydrolysis of beta-D
      xylopyranosylamine was studied using 13C-labeled substrates to establish optimal
      solution conditions for cyanohydrin formation. Major hydrolytic intermediates
      were observed and identified by time-lapse 1D and 2D NMR analyses of reaction
      mixtures. The aldopentosylamines were subsequently employed in cyanohydrin
      reduction reactions with K13CN to yield C2-epimeric [1-13C]2-aminosugars, which
      were separated by chromatography on ion-exchange columns. N-Acetylation and
      methyl glycosidation followed by chromatography gave pure 2-acetamido-2-deoxy-D
      [1-13C]aldohexopyranosides. J(CH) and J(CC) spin-spin coupling constants
      involving the labeled anomeric carbon were measured and compared to those
      observed previously in methyl D-[1-13C]aldohexopyranosides. In parallel studies,
      theoretical J-couplings were calculated in model N-acetylated aldopyranosides
      using density functional theory (DFT) to predict the effect of OH vs NHCOCH(3)
      substitution at C2 on J(CH) and J(CC) values in aldopyranosyl rings. The
      synthetic method was also modified to accommodate (15)N- and (13)C-labeling
      within the N-acetyl side-chain, and some J-couplings involving 1H, 13C, and 15N
      atoms in 2-[1,2-13C2;15N]acetamido-2-deoxy-D-[1-13C]glucose were measured and
      interpreted.

PMID- 16408954
TI  - Synthesis of a NO-releasing prodrug of rofecoxib.
AB  - [reaction: see text] A newly developed synthesis of a NO-releasing prodrug of
      rofecoxib is described. The highly productive process consists of five chemical
      steps and produces prodrug 1 in an overall 64% yield from commercially available
      3-phenyl-2-propyn-1-ol (4). The synthesis is highlighted by the carbometalation
      reaction of propargyl alcohol 4 to generate the tetrasubstituted olefin core,
      sulfone acid 2. Additionally, two alternate end-game strategies to prepare NO
      COXIB 1 from this intermediate were explored and developed: (1) a convergent
      synthesis where a bromonitrate side chain is introduced in one step and (2) a two
      step sequence that first installs the requisite six-carbon ester side chain
      followed by chemoselective nitration.

PMID- 16408955
TI  - Cladobotric acids A-F: new cytotoxic polyketides from a New Zealand Cladobotryum
      sp.
AB  - [reaction: see text] Cladobotric acids A-F (1-6), fungal-derived polyketides,
      were isolated from the fermentation broth of a New Zealand Cladobotryum species.
      Structures were determined by extensive spectral analysis and X-ray
      crystallography, and the polyketide origin of 1-6 was concluded from feeding
      experiments with (13)C-labeled precursors. The observed folding pattern for the
      polyketide chain is unusual for fungi. Cladobotric acids A-F (1-6) exhibited
      notable cytotoxicity against the murine P388 leukemia cell line and were also
      active against Bacillus subtilis and Candida albicans.

PMID- 16408956
TI  - Synthesis and reactivity of new chiral bicyclic phospholanes as acyl-transfer
      catalysts.
AB  - [structure: see text] Synthesis of chiral phosphines 1a, 14a, and 18a as
      nucleophilic catalysts for anhydride activation and kinetic resolution of
      alcohols is described. Radical cyclization of alkenylphosphines produced the
      phosphabicyclooctane (PBO) core of catalysts 1a and 14a, while 18a was made by
      quenching a metallocycle precursor with dichlorophenylphosphine. Catalysts 1a and
      14a are less reactive, while 18a is comparable to the most reactive catalysts in
      the PBO family. The preferred ground-state geometries of phosphine-boranes were
      identified using computational methods, and were correlated with the catalytic
      reactivity of the corresponding free phosphines.

PMID- 16408957
TI  - Methyl ether derivatives of p-tert-Butyl[3.1.3.1]homooxacalixarene. Formation,
      structure, and complexes with quaternary ammonium ions.
AB  - [structure: see text] The whole set (five compounds) of partially O-methylated
      products of p-tert-butyl[3.1.3.1]homooxacalixarene, currently named p-tert
      butyltetrahomodioxacalix[4]arene, have been prepared. Their structure has been
      investigated in solution through NMR techniques and in the solid state by single
      crystal X-ray diffraction. A systematic investigation, extended to the parent
      tetraphenol and to the tetramethyl ether derivative, has been carried out on the
      complexation of tetramethylammonium, acetylcholine, N-methylpyridinium, and
      tetraethylammonium picrate in CDCl3. The observed trends in the binding and in
      the selectivity of the strictly related hosts could be analyzed on the basis of
      the varying importance of intramolecular hydrogen bonding and its effects on the
      conformation of the free and of the complexed ligands. On increasing the number
      of methyl ether functions, the cone conformation appears to be relatively less
      stable but deeper, so small organic cations can be more effectively encircled.

PMID- 16408958
TI  - Synthesis and structural investigation of internally coordinated alpha
      amidoboronic acids.
AB  - [structure: see text] Six new N-acyl-boroGly derivatives, along with their N-acyl
      boroSar analogues, have been synthesized by modification of conventional
      procedures. Structural characterization of these alpha-amidoboronic acids was
      accomplished by extensive use of 11B and 1H NMR spectroscopy. These compounds
      were prepared to determine the extent of intramolecular B-O dative bond formation
      within the context of a five-membered (:O=C-N-C-B) ring motif. It is shown that
      the formation of such dative bonds depends on the nature of the substituents at
      both the acyl carbon and the nitrogen atoms. Computational evidence from second
      order Moller-Plesset perturbation theory is provided in support of these
      findings.

PMID- 16408959
TI  - Steric modulations in the reversible dimerizations of phenalenyl radicals via
      unusually weak carbon-centered pi- and sigma-bonds.
AB  - [reaction: see text] Spontaneous self-associations of various tricyclic
      phenalenyl radicals lead reversibly to either pi- or sigma-dimers, depending on
      alkyl-substitution patterns at the alpha- and beta-positions. Thus, the
      sterically encumbered all-beta-substituted tri-tert-butylphenalenyl radical (2*)
      affords only the long-bonded pi-dimer in dichloromethane solutions, under
      conditions in which the parent phenalenyl radical (1*) leads to only the sigma
      dimer. Further encumbrances of 1* with a pair of alpha, beta- or beta, beta- tert
      butyl substituents and additional methyl and ethyl groups (as in sterically
      hindered phenalenyl radicals 3* - 6*) do not inhibit sigma-dimerization. ESR
      spectroscopy is successfully employed to monitor the formation of both
      diamagnetic (2-electron) dimers; and UV-vis spectroscopy specifically identifies
      the pi-dimer by its intense near-IR band. The different temperature-dependent
      spectral (ESR and UV-vis) behaviors of these phenalenyl radicals allow the
      quantitative evaluation of the bond enthalpy of 12 +/- 2 kcal mol(-1) for sigma
      dimers, in which the unusually low value has been theoretically accounted for by
      the large loss of phenalenyl (aromatic) pi-resonance energy attendant upon such
      bond formation.

PMID- 16408960
TI  - Rational synthesis of meso- or beta- fluoroalkylporphyrin derivatives via halo
      fluoroalkylporphyrin precursors: electronic and steric effects on regioselective
      electrophilic substitution in 5-fluoroalkyl-10,20-diarylporphyrins.
AB  - [reaction: see text] Electrophilic nitration, formylation or bromination of
      metalated 5-fluoroalkyl-10,20-diphenylporphyrin (fluoroalkyl = CF3, ClCF2CF2, n
      C6F13) proceeded with high regioselectivity, exclusively affording corresponding
      meso-substituted porphyrins, while the iodination reaction mainly took place at
      the adjacent beta site giving 2-iodo-10-fluoroalkyl-5,15-diphenylporphyrin.
      Suzuki, Sonogashira, and trifluoromethylation reactions of the obtained 5-bromo
      15-fluoroalkyl-10,20-diphenylporphyrins or 2-iodo-10-fluoroalkyl-5,15
      diphenylporphyrins could perform smoothly to give the corresponding various meso-
      or beta-functionalized fluoroalkylated porphyrin derivatives. Accordingly, two
      meso-to-meso butadiyne-bridged bisporphyrin dimers and two beta-to-beta butadiyne
      linked dimeric porphyrins were prepared by the coupling reactions of 5-ethynyl-15
      fluoroalkyl-10,20-diphenylporphyrins and 2-ethynyl-10-fluoroalkyl-5,15
      diphenylporphyrins, respectively.

PMID- 16408961
TI  - Magnetic nanoparticles as an orthogonal support of polymer resins: applications
      to solid-phase suzuki cross-coupling reactions.
AB  - [reaction: see text] Most of the reactants immobilized on conventional solid
      phase resins are buried inside the interiors of lightly cross-linked polystyrene
      beads. An orthogonal support of solid-phase resins needs to be small enough to
      penetrate the interpolymeric chain spaces of a swollen resin to reach reaction
      sites. In this paper, we report the use of magnetic nanoparticles ( approximately
      4 nm) as an orthogonal matrix to assist solid-phase reactions. A magnetic
      nanoparticle-supported homogeneous Pd catalyst was employed for promoting the
      Suzuki cross-coupling of an aryl halide on resins and an excessive arylboronic
      acid in solution. The workup separating three components (the catalyst, product,
      and remaining arylborate) is a chromatography-free process. The Pd catalyst was
      magnetically isolated and recycled from the reaction mixture by applying an
      external magnetic field. Then, a filtration process was followed to recover the
      excess borate reagent from the resins/product. Our work here presents the first
      example of an orthogonal matrix of solid-phase resins and shows the promise of
      employing nanomaterials in organic synthesis.

PMID- 16408962
TI  - Iridium complex-catalyzed [2+2+2] cycloaddition of alpha,omega-diynes with
      monoynes and monoenes.
AB  - [reaction: see text] [Ir(cod)Cl]2/DPPE was found to be a new catalyst for the
      cycloaddition of alpha,omega-diynes with monoynes to give polysubstituted benzene
      derivatives in high yields. Internal monoynes as well as terminal monoynes could
      be used. The reaction tolerates a broad range of functional groups such as
      alcohol, amine, alkene, ether, halogen, and nitrile. The reaction of 1,6
      octadiyne derivatives with 1-alkynes gives ortho products and meta products. The
      regioselectivity could be controlled by the choice of ligand. The reaction with
      DPPE was meta selective, with meta selectivity of up to 82%. The reaction with
      DPPF was ortho selective, with ortho selectivity of up to 88%. We propose a
      mechanism to account for this regioselective cycloaddition. [Ir(cod)Cl](2)/DPPE
      also catalyzed the cycloaddition of alpha,omega-diynes with 2,5-dihydrofuran to
      give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and
      n-butyl vinyl ether gave benzene derivatives instead of cyclohexadiene
      derivatives. We also propose a mechanism to account for this novel aromatization
      that includes cleavage of the C-O bond.

PMID- 16408963
TI  - Studies of the condensation of sulfones with ketones and aldehydes.
AB  - [reaction: see text] The condensation of ketones or aldehydes with sulfones was
      shown to give a variety of products. Condensation of 2-methylcyclohexanone with
      dimethyl sulfone using potassium t-butoxide as base gave useful yields of 1,2
      dimethylenecyclohexane. Under the same conditions, cycloheptanone, 3-methyl-2
      butanone, and 2-butanone were converted to dienes. Remarkably, these reaction
      conditions converted acetophenone into p-terphenyl (10%) and (E)-1,4-diphenyl-3
      penten-1-one (44%). Propiophenone was converted to 2'-methyl-p-terphenyl (61%).
      Using alpha-tetralone produced 1-methynaphthalene and naphthalene. No reaction
      took place with beta-tetralone. Using diethyl sulfone with alpha-tetralone lead
      to pure naphthalene. Condensation of isobutyraldehyde and dimethyl sulfone using
      potassium t-butoxide gave isoprene in low yield. Using benzaldehyde and benzyl
      phenyl sulfone in N,N-dimethylacetamide gave 1,2-diphenyl-1
      phenylsulfonylethylene, N,N-dimethylcinnamide, and a complex condensation
      product. Only 1,2-diphenyl-1-phenylsulfonylethylene was obtained when the solvent
      was THF.

PMID- 16408964
TI  - Rate constants for anilidyl radical cyclization reactions.
AB  - [reaction: see text] N-Aryl-5,5-diphenyl-4-pentenamidyl radicals (3) were
      produced by 266 nm laser-flash photolysis of the corresponding N-(phenylthio)
      derivatives, and the rate constants for the cyclizations of these radicals were
      measured directly. The 5-exo cyclization reactions were fast (k(c) > 2 x 10(5) s(
      1)), and radicals 3 generally behaved as electrophilic reactants with a Hammett
      correlation of rho = 1.9 for five of the six radicals studied. However, the p
      methoxyphenyl-substituted radical 3f cyclized much faster than expected from the
      Hammett analysis. Variable temperature studies of parent radical 3a (aryl =
      phenyl) gave an Arrhenius function with log k = 9.2 - 4.4/2.3RT (kcal/mol). The
      rate constant for the reaction of p-ethylphenyl-substituted anilidyl radical 3b
      with Bu(3)SnH at 65 degrees C was k(T) = 4 x 10(5) M(-1) s(-1).

PMID- 16408965
TI  - Biosynthetic studies on the botcinolide skeleton: new hydroxylated lactones from
      Botrytis cinerea.
AB  - [reaction: see text] The biosynthetic origin of the botcinolide skeleton was
      investigated by means of feeding 13C- and 2H-labeled precursors to Botrytis
      cinerea. Three new compounds, two homobotcinolide derivatives, 3-O
      acetylhomobotcinolide (5) and 8-methylhomobotcinolide (6), and a new 11-membered
      lactone (7), were isolated. Their structures were elucidated on the basis of
      spectroscopic data, including one-bond and long-range 1H-13C correlations. The
      relative stereochemistries were determined by combined analyses of NOE data and
      1H-1H coupling constants. According to the results of feeding experiments with
      13C- and 2H-labeled acetate and l-S-methylmethionine, 5 is an acetate-derived
      polyketide whose methyl groups originate from l-S-methylmethionine. This is a
      rare example of the incorporation of a methyl from methionine into a supposed C3
      starter unit of the polyketide synthesis.

PMID- 16408966
TI  - Pyrrolidine-containing polypyridines: new ligands for improved visible light
      absorption by ruthenium complexes.
AB  - [reaction: see text] A range of new electron-releasing pyrrolidine-containing
      bipyridines and terpyridines has been prepared via selective metalation-cross
      coupling sequences. The obtained ligands have been involved in microwave-assisted
      ruthenium complexation leading to homoleptic complexes in high yield. The
      electron-donor effect of the pyrrolidine nucleus led to a notable improvement of
      visible light absorption and strong changes in the electrochemical behavior,
      opening new opportunities for the design of photovoltaic devices.

PMID- 16408967
TI  - Synthesis of diazeniumdiolates from the reactions of nitric oxide with enolates.
AB  - [reaction: see text] Reactions of nitric oxide with enolates derived from
      aliphatic methyl ketones containing alpha-methylene or alpha-methine groups and
      with enolates derived from alpha,alpha'-dimethylene or alpha,alpha'-dimethine
      ketones yield mono- or bis(diazeniumdiolate) products. Diazeniumdiolation occurs
      in the following order: alpha-methine > alpha-methylene > alpha-methyl. The
      amount of the base used alters the extent of diazeniumdiolation and the course of
      the reaction. Mono- and bis(diazeniumdiolate)-substituted methyl ketones are
      cleaved in the presence of excess base before and after the subsequent
      diazeniumdiolation of the alpha-methyl group. Similar to the trihalogenated
      methyl groups in the base-assisted halogenation reactions of methyl ketones, the
      bis(diazeniumdiolate)-substituted alpha-methylene and alpha-methyl groups act as
      leaving groups in the presence of excess base. The reaction of nitric oxide with
      a (approximately 20:80, cis/trans) mixture of 2,6-cyclohexananone yields the cis
      and trans isomers of 2,6-dimethylcyclohexanone-2,6-bis(diazeniumdiolate) in 12.9%
      and 57.6% yield. Single-crystal X-ray diffraction data determined for potassium
      cis-2,6-dimethylcyclohexanone-2,6-bis(diazeniumdiolate), cis-14b, reveal that the
      N(2)O(2-) substituent is planar with considerable delocalization of a double bond
      over the anionic four-atom group. Except for one of the diazeniumdiolate
      products, namely, potassium propanoate 2,2-bis(diazeniumdiolate), 8b, all are
      stable in neutral and basic aqueous media. Compound 8b slowly decomposes in
      neutral aqueous solution releasing nitrous oxide and nitric oxide gases but is
      stable in basic aqueous media. Differential scanning calorimetry data measured
      for the diazeniumdiolate products indicate that they decompose exothermally with
      most of them undergoing explosive decomposition at moderately high temperatures
      (181-274 degrees C).

PMID- 16408968
TI  - Theoretical study of reactant activation in 1,3-dipolar cycloadditions of cyclic
      nitrones to free and Pt-bound nitriles.
AB  - [reaction: see text] 1,3-Dipolar cycloaddition of the cyclic nitrones
      CH2(CH2)2CH=NO (N1), CH2CH2OCH=NO (N2), CH2-OCH2CH=NO (N3), and O(CH2)2CH=NO (N4)
      to organonitriles, RCN-both free (R = CH(3), CF(3)) and ligated to Pt(II) and
      Pt(IV) (in the complexes trans-[PtCl(2)(NCCH(3))(2)] (1) and trans
      [PtCl(4)(NCCH(3))(2)] (2))-was investigated extensively by theoretical methods at
      different levels of theory. The effectiveness of two types of dipolarophile
      activation (by introducing a strong electron-acceptor group R and by coordination
      to a metal center) was analyzed and compared. The influence of factors such as
      the nature of the cyclic nitrone and the nature of the solvent on the reactions
      was also studied. The reactivity of dipoles and dipolarophiles increases along
      the series N4 < N1 approximately N3 < N2 and CH(3)CN < CF(3)CN < 1 < 2; the
      latter demonstrates that the coordination of RCN to a Pt center provides an even
      higher activation effect upon cycloaddition in comparison with the introduction
      of a strong electron-acceptor group R such as CF(3). A higher reactivity of the
      cyclic dipole N1 in comparison with acyclic nitrones (e.g., CH(3)CH=N(CH(3))O) is
      interpreted to be a result of its exclusive existence in a more strained and
      hence more reactive E- rather than Z-configuration. The activation and reaction
      energies have been calculated at different basis sets and levels of theory, up to
      MP4(SDTQ), CCSD(T), and CBS-Q. The activation energies are weakly sensitive to a
      change of the correlated methods. The consideration of the solvent effects
      results in the increase of the activation barriers, and such enhancement is less
      pronounced for the nonpolar or low polar solvents. The cycloadditions to CH(3)CN
      and CF(3)CN were found to be nearly synchronous, but these reactions involving 1
      and 2 are clearly asynchronous. Moreover, the reaction of N2 with 2 proceeds via
      a very early acyclic transition state, while for all other reactions the
      transition states have a cyclic nature.

PMID- 16408970
TI  - Enantiopure O-substituted phenylphosphonothioic acids: chiral recognition ability
      during salt crystallization and chiral recognition mechanism.
AB  - [structure: see text] The chiral recognition ability of enantiopure O-methyl, O
      ethyl, O-propyl, and O-phenyl phenylphosphonothioic acids (1a-d) for various
      kinds of racemic amines during salt crystallization and the chiral recognition
      mechanism were thoroughly investigated. The chiral recognition abilities of
      enantiopure 1a-d for a wide variety of racemic amines varied in a range of 6 to
      >99% enantiomeric selectivity. Deposited less-soluble diastereomeric salts were
      classified into two categories, prism- and needle-type crystals; the prism-type
      crystals were composed of a globular molecular cluster, while there existed a
      2(1) column in the needle-type crystals. In contrast to a general observation of
      a similar 2(1) column in the less-soluble diastereomeric salt crystals of chiral
      primary amines with chiral carboxylic acids, the globular molecular cluster is a
      very unique hydrogen-bonding motif that has never been constructed in
      diastereomeric salt crystals. Excellent chiral recognition was always achieved
      when the less-soluble diastereomeric salts were prism-type crystals. Significant
      correlations were found between the degree of the chiral recognition with 1a-d,
      the crystal shape of the less-soluble diastereomeric salts, and the hydrogen
      bonding motif (molecular cluster/2(1) column). The chiral recognition mechanisms
      via the molecular cluster and the 2(1) column formations are discussed in detail
      on the basis of X-ray crystallographic analyses.

PMID- 16408969
TI  - Tandem double-intramolecular [4+2]/[3+2] cycloadditions of nitroalkenes. Studies
      toward a total synthesis of daphnilactone B: piperidine ring construction.
AB  - [reaction: see text] Two model studies in support of a total synthesis of the
      complex polycyclic alkaloid daphnilactone B have been completed. The objectives
      of the models studies were to demonstrate the use of a tandem double
      intramolecular [4+2]/[3+2] nitroalkene cycloaddition for the stereocontrolled
      construction of four of the rings in the core of the natural product. The first
      model study established the ability to create a pyrrolidine ring corresponding to
      ring A of daphnilactone B through a modification of the dipolarophile and
      subsequent functional group manipulations. The second model study required the
      modification of the dienophile in the [4+2] cycloaddition to accommodate the
      formation of a piperidine ring (ring B of daphnilactone B). Nitroalkene 26
      containing a diene as the dienophile served well in the tandem cycloaddition to
      afford the nitroso acetal 38a in 77% yield. Subsequent functional group
      manipulations allowed for the high-yielding conversion to the core of
      daphnilactone B.

PMID- 16408971
TI  - Toward an intimate understanding of the structural properties and conformational
      preference of oxoesters and thioesters: gas and crystal structure and
      conformational analysis of dimethyl monothiocarbonate, CH3OC(O)SCH3.
AB  - [structure: see text] The molecular structure and conformational properties of
      dimethyl monothiocarbonate, CH3OC(O)SCH3, have been studied in the gas phase by
      gas electron diffraction (GED) and vibrational spectroscopy and in the solid
      state by X-ray crystallography. The experimental investigations were supplemented
      by quantum chemical calculations at the B3LYP/6-311++G(3df,2p) and MP2/6
      311++G(2df,p) levels of approximation. The gaseous molecule exhibits only one
      conformation having Cs symmetry with synperiplanar orientation of both the C-S
      and the C-O single bonds relative to the C=O double bond. The following skeletal
      geometric parameters were derived from the GED analysis (r(hl) values with 3sigma
      uncertainties): C=O = 1.203(4) A, C(sp(2))-O = 1.335(5) A, C(sp(3))-O = 1.437(5)
      A, C(sp(2))-S = 1.763(5) A, and C(sp(3))-S = 1.803(5) A; O=C-O = 125.9(8) degrees
      , O=C-S = 125.7(7) degrees , O-C-S = 108.4(9) degrees , and C-O-C = 113.4(15)
      degrees . The structure of a single crystal, grown by a miniature zone-melting
      procedure, was determined by X-ray diffraction analysis at a low temperature. The
      crystalline solid [monoclinic, P2(1)/n, a = 12.6409(9) A, b = 4.1678(3) A, and c
      = 19.940(1) A, beta = 98.164(1) degrees ] exists exclusively as molecules in the
      synperiplanar conformation and with geometrical parameters that agree with those
      of the molecule in the gas phase. The results are discussed in terms of anomeric
      and mesomeric effects and in terms of a natural bond orbital analysis.

PMID- 16408972
TI  - Catalytic reduction and intramolecular cyclization of haloalkynes in the presence
      of nickel(I) salen electrogenerated at carbon cathodes in dimethylformamide.
AB  - [reaction: see text] Pentylidenecyclopentane can be conveniently prepared in up
      to 86% yield via the catalytic reduction of 1-iodo- or 1-bromo-5-decyne by [[2,2'
      [1,2-ethanediylbis(nitrilomethylidyne)]bis[phenolato]]-N,N',O,O']nickelate(I)
      electrogenerated at a carbon cathode in dimethylformamide containing
      tetramethylammonium tetrafluoroborate. This electrosynthesis can be accomplished
      at potentials for which the haloalkynes are electroinactive, and it can be
      completed within 30 min at room temperature. Attempts to synthesize
      pentylidenecyclobutane and pentylidenecyclohexane from 1-halo-4-nonynes and 11
      halo-5-undecynes, respectively, under similar conditions afford the carbocycles
      in very low yields (2% and 6%, respectively). Other products derived from the
      various haloalkynes are dimers, alkynes, and 1-alkenynes. Dimers (alkadiynes)
      arising from 1-halo-4-nonynes and 11-halo-5-undecynes are formed in yields
      ranging from 80% to 89%, whereas icosa-5,15-diyne (the dimer obtained from a 1
      halo-5-decyne) is found in significantly lower yield (</=13%). Alkynes and 1
      alkenynes are produced in yields of 3-10% and 2-3%, respectively. A mechanistic
      scheme, involving alkyn-1-yl radicals arising from nickel(I) salen catalyzed
      cleavage of the carbon-halogen bond of each haloalkyne, is proposed to account
      for the formation of all products.

PMID- 16408974
TI  - Formal total synthesis of neocarzinostatin chromophore.
AB  - [reaction: see text] An efficient route to the neocarzinostatin chromophore
      aglycon has been developed. The present strategy involves a stereoselective
      intramolecular acetylide-aldehyde cyclization to form the C5-C6 bond, followed by
      efficient installation of alpha-epoxide, naphthoate, and carbonate
      functionalities. The C8-C9-olefin was introduced by using the Martin sulfurane
      dehydration reaction to furnish the highly reactive aglycon.

PMID- 16408973
TI  - Synthesis of photoactivatable analogues of lysophosphatidic acid and covalent
      labeling of plasma proteins.
AB  - [reaction: see text] Lysophosphatidic acids bearing a benzophenone group in
      either the sn-1 or sn-2 chain of an oleoyl-type ester or oleyl-type ether chain
      and (32)P in the phosphate group were synthesized. The benzophenone moiety was
      introduced by selective hydroboration of the double bond of enyne 11 at low
      temperature, followed by a Suzuki reaction with 4-bromobenzophenone. The key
      intermediates for the preparation of ester-linked lysophosphatidic acid (LPA) 1
      and 3 were obtained in one pot by a modified DIBAL-H reduction of orthoformate
      intermediate 22. These probes were shown to covalently modify a single protein
      target in rat plasma containing albumin and several protein targets in rat plasma
      containing a low level of albumin.

PMID- 16408975
TI  - Tetracoordinate carbon as a nucleophile? Interconversion of carbenium ions with
      carbonium ions possessing nearly square-pyramidal pentacoordinate carbons.
AB  - [structure: see text] Quantum chemical calculations (B3LYP and Moeller-Plesset
      second-order perturbation theory) on carbonium ions containing hypercoordinated
      carbon atoms in distorted square-pyramidal geometries are described. The
      importance of overall charge (in addition to the delocalization of a certain
      number of electrons) for the stability of such structures is explored through
      calculations on isoelectronic systems containing boron atoms. The effects of
      alkyl substitution as well as variations in the structure of the linker attached
      to the C(5) core substructure are explored systematically for a variety of
      structures that do not have severe geometric constraints that rigidly enforce
      unusual geometries. In addition, transition structures for reactions involving
      the intramolecular attack of tetracoordinate carbons on carbenium ion centers
      were located; in some cases, such carbenium-to-carbonium rearrangement processes
      (in which tetracoordinate carbon centers act as nucleophiles) are actually both
      exothermic and accompanied by low activation barriers.

PMID- 16408976
TI  - Cobalt-catalyzed reductive coupling of saturated alkyl halides with activated
      alkenes.
AB  - [reaction: see text] An efficient cobalt-catalyzed reductive coupling reaction of
      alkyl halides with electron-withdrawing alkenes (CH(2)=CR(1)EWG, EWG = electron
      withdrawing group) in the presence of water and zinc powder in acetonitrile to
      give the corresponding Michael-type addition product (RCH(2)CR(1)EWG) was
      described. The methodology is versatile such that unactivated primary, secondary,
      and tertiary alkyl bromides and iodides and various conjugated alkenes including
      acrylates, acrylonitrile, methyl vinyl ketone, and vinyl sulfone all successfully
      participate in this coupling reaction. For the alkyl halides used in the
      reaction, the iodides generally gave better yields compared to those of the
      corresponding bromides. It is a unique method employing CoI(2)dppe, zinc, and
      alkyl halides, affording conjugate addition products in high yields.
      Mechanistically, the reaction appears to follow an oxidative addition driven
      route rather than the previously reported radical route.

PMID- 16408977
TI  - Syntheses, structures, and thermolyses of pentacoordinate 1,2-oxastibetanes:
      potential intermediates in the reactions of stibonium ylides with carbonyl
      compounds.
AB  - [reaction: see text] Pentacoordinate 1,2-oxastibetanes 14a-d, which are formal [2
      + 2]-cycloadducts of the reactions of stibonium ylides with carbonyl compounds,
      were successfully synthesized by the reactions of the corresponding bromo-2
      hydroxyalkylstiboranes with NaH. The crystal structures of 14a and 14c were
      established by X-ray crystallographic analyses, showing their distorted trigonal
      bipyramidal structures and smaller C-Sb-O angles of the four-membered ring around
      antimony than the C-P-O angle of pentacoordinate 1,2-oxaphosphetane 3. The 1H,
      13C, and 19F NMR spectra of 14a-d are consistent with the trigonal bipyramidal
      structure in the solution state. Although 14a did not decompose at all at 220
      degrees C in o-xylene-d(10), the thermolyses of 3-phenyl-1,2-oxastibetane 14c
      were carried out at 220 degrees C in o-xylene-d(10) and at 140 degrees C in
      acetonitrile-d(3) to give the corresponding oxirane 28 with retention of
      configuration and cyclic stibinite 25. The formation of 28 is explained by apical
      equatorial ligand coupling around antimony via a polar transition state, which is
      more favorable than olefin formation. In contrast, the thermolyses of 14c in the
      presence of LiBr and LiBPh4 gave oxirane 29 with inversion of configuration and
      the olefin 30, respectively. The formation of 29 and 30 is considered to proceed
      via an anti-betaine-type intermediate and hexacoordinate 1,2-oxastibetanide 36,
      respectively. Selective formation of 28, 29, and 30 in the thermolyses of 14c,
      which is regarded as an intermediate in the reaction of an alpha-phenyl
      substituted stibonium ylide with a carbonyl compound, showed that the change of
      the reaction conditions controls the reactivity of a 1,2-oxastibetane compound.

PMID- 16408978
TI  - Synthesis of functionalized benzylsilanes from arylzinc compounds and
      (iodomethyl)trimethylsilane by means of a novel Rh catalysis.
AB  - [reaction: see text] The catalytic activity of a Rh complex in cross-coupling
      between ArZnI and TMSCH2I was examined in which the Rh complex, generated in situ
      from [RhCl(1,5-cyclooctadiene)]2 and 1,1'-bis(diphenylphosphino)ferrocene,
      exhibited excellent catalytic activity for the production of various
      functionalized benzylsilanes in good yields. From 31P NMR studies of various
      solutions containing several of the reaction components, confirmation of the
      rapid and quantitative transfer of aryl groups from ArZnI to the Rh complex to
      form arylrhodium species was ascertained. A catalytic cycle, commencing with the
      transmetalation, was thus proposed for the reaction.

PMID- 16408979
TI  - Photoinduced 1,4-additions of indoles to enones.
AB  - [reaction: see text] A photoinduced procedure for the 1,4-addition of indoles to
      enones is described. This reaction occurs with modest to excellent yield for
      cyclic and some acyclic enones. This reaction is experimentally simple, requiring
      only irradiation (UVA lamps, ca. 350 nm) of the reagents in a CH2Cl2 solution at
      room temperature, and avoids the necessity to use a Lewis acid. An important
      solvent effect was noticed, with CH2Cl2 and CHCl3 being the optimal solvents.
      Various substituents are tolerated on the indole moiety and an electronic trend
      was noticed, as electron-withdrawing groups can suppress this reaction. A
      mechanism involving single electron transfer between the enone triplet excited
      state and the indole is proposed and accounts for all experimental observations.

PMID- 16408980
TI  - Novel reactions of [60]fullerene with amino acid esters and carbon disulfide.
AB  - [reaction: see text] Novel reactions of C60 with amino acid ester hydrochlorides
      and CS2 in the presence of Et3N affording fullerene derivatives 2 and 3
      containing biologically active amino acids, thioamide, and thiourea units have
      been investigated. The thioamide groups in compounds 2 are sensitive to moisture
      and can easily be hydrolyzed to amide groups.

PMID- 16408981
TI  - Suzuki-Miyaura, alpha-ketone arylation and dehalogenation reactions catalyzed by
      a versatile N-heterocyclic carbene-palladacycle complex.
AB  - [reaction: see text] The activity of the complex (IPr)PdCl(eta2-N,C-C12H7NMe2), 1
      [IPr = (N,N'-bis(2,6-diisopropylphenyl)imidazol)-2-ylidene], in the Suzuki
      Miyaura cross-coupling reaction involving unactivated aryl chlorides and
      triflates with arylboronic acids at room temperature in technical grade 2
      propanol is described. These conditions allow for the synthesis of di- and tri
      ortho-substituted biaryls in very short reaction times. This complex also
      displays very high activity for alpha-ketone arylation and dehalogenation
      reactions of activated and unactivated aryl chlorides.

PMID- 16408982
TI  - Diastereoselective synthesis of all eight l-hexoses from L-ascorbic acid.
AB  - [reaction: see text] A novel versatile method for the synthesis of all eight
      diastereomerically pure L-hexoses was developed. L-Ascorbic acid was converted to
      two diastereomers A. These alpha-hydroxy esters were transformed into four gamma
      alkoxy-alpha,beta-unsaturated esters C via the intermediates B and subsequent
      Wittig olefination reactions. Each one of compounds C was subjected to
      dihydroxylation to provide a set of two diols D. Anti/syn-differentiation in diol
      formation was manipulated by using (DHQD)2PHAL and (DHQ)2PHAL as chiral ligands.
      Further two-step reaction sequence affords all eight diastereopure L-hexoses.

PMID- 16408983
TI  - Intramolecular additions of various pi-nucleophiles to chemoselectively activated
      amides and application to the synthesis of (+/-)-tashiromine.
AB  - [reaction: see text] Vilsmeier-Haack type cyclizations proved to be particularly
      efficient for generating parts of the polycyclic cores of many alkaloids,
      although only monocyclizations have so far been reported. With the goal of
      rapidly and efficiently constructing polycyclic alkaloids, we decided to exploit
      the Vilsmeier-Haack reaction by utilizing iminium ions successively generated and
      trapped with tethered nucleophiles. To develop such a strategy, we had to set the
      first cyclization. This constitutes a great challenge in itself because amide
      activation conditions are usually not compatible with tethered nucleophiles,
      except for indoles and aromatic rings which have already been reported. This
      paper describes the comprehensive study of intramolecular addition of silyl enol
      ethers, allylsilanes, and enamines to chemoselectively activated formamides,
      aliphatic amides, and lactams. Good to excellent yields were obtained for the 5
      exo, 6-exo, and 6-endo modes of cyclization. Moreover, we demonstrated that the
      species in solution after the cyclization are iminium ions. This is highly
      encouraging for the development of bis-cyclization strategies. An expeditious
      total synthesis of (+/-)-tashiromine is also reported.

PMID- 16408985
TI  - Ring-opening metathesis polymer sphere-supported seco-porphyrazines: efficient
      and recyclable photooxygenation catalysts.
AB  - [reaction: see text] Crossover Linstead macrocyclization of norbornenyl-tagged
      diaminomaleonitrile with dipropylmaleonitrile gave the corresponding magnesium
      diaminohexapropylporphyrazine, which was subsequently converted into its zinc
      seco-derivative. Polymerization gave the corresponding ROMPgel and ROMPsphere
      (ROMP = ring-opening metathesis polymer) reagents, the latter of which proved
      efficient as an immobilized catalyst for the sensitized production of singlet
      oxygen for the purification-minimized parallel synthesis of endoperoxides and ene
      adducts.

PMID- 16408984
TI  - Chain mechanism in the photocleavage of phenacyl and pyridacyl esters in the
      presence of hydrogen donors.
AB  - [reaction: see text] Excited phenacyl and 3-pyridacyl esters of benzoic acid
      react with an excess of aliphatic alcohols in a chain reaction process involving
      hydrogen transfer from the ketyl radical intermediates, leading to benzoic acid
      in addition to acetophenone and 3-acetylpyridine, respectively, as the
      byproducts. While the maximum quantum yields reached 4 in both cases, the 2- or 4
      pyridacyl ester photoreduction proceeded with the efficiency below 100% under the
      same conditions. The investigation indicates that a radical coupling between
      ketyl radicals, both formed from the excited ester by hydrogen abstraction from
      an alcohol, is accompanied by the elimination of benzoic acid from the ester
      ketyl radical itself. A partitioning between two reactions was found to be
      remarkably sensitive to the chromophore nature, such as a position of the
      nitrogen atom in the pyridacyl moiety. The magnitude of a radical chain process
      is dependent on the efficiency of consecutive steps that produce free radicals
      capable of a subsequent ester reduction. The driving force of a possible electron
      transfer from the ketyl radicals to the ester has been excluded on the basis of
      cyclic voltametry measurements. The observed quantum yields of photoreduction
      were found to be diminished by formation of relatively long-lived light absorbing
      transients, coproducts obtained apparently by secondary photochemical reactions.
      Additionally, it is shown that basic additives such as pyridine can further
      increase the efficiency of the photoreduction by a factor of 4. A radical nature
      of the reduction mechanism was supported by finding a large kinetic chain length
      of an analogous reaction initiated by free radicals generated thermally yet again
      when phenacyl or 3-pyridacyl benzoate was used. Both phenacyl and pyridacyl
      chromophores are pronounced to be valuable as the photoremovable protecting
      groups when high quantum and chemical yields of carboxylic acid elimination are
      important, but higher concentrations of the hydrogen atom donors are not
      destructive for a reaction system or are experimentally impractical.

PMID- 16408987
TI  - Selective catalytic oxidative carbonylation of amino alcohols to ureas.
AB  - [reaction: see text] Amino alcohols undergo W(CO)(6)-catalyzed oxidative
      carbonylation to the corresponding hydroxyalkylureas without protection of the
      hydroxyl group. Selected examples of 1,2-, 1,3-, 1,4-, and 1,5-amino alcohols
      were converted to the ureas in good to excellent yields, with only small amounts
      of the cyclic carbamates being formed. In contrast, the phosgene derivatives CDI
      and DMDTC undergo stoichiometric reactions with the amino alcohol substrates to
      afford ureas and cyclic carbamates with variable selectivity.

PMID- 16408986
TI  - Direct cyclopropanation of 1-alkynylphosphonates by Cp2ZrCl2/2EtMgBr/2AlCl3 to
      afford cyclopropylmethylphosphonates.
AB  - [reaction: see text] The reagent system Cp2ZrCl2/2EtMgBr/2AlCl3 converts 1
      alkynylphosphonates into cyclopropylmethylphosphonates 3 in good isolated yields.
      Ethers, chlorides, and other cyclopropyl groups are compatible with the reaction
      conditions. Deuterium labeling is consistent with the formation of stable
      cyclopropylmethylbimetallic phosphonates by ring contraction of the corresponding
      aluminacyclopentenylphosphonate. Temperature is crucial; apparently, the
      cyclopropylmethylbimetallic phosphonates are in equilibrium with the
      aluminacyclopentenylphosphonates. Low temperature favors the former. We surmise
      that the negative charges of the intermediate are stabilized by the phosphonate
      group. Thus, diphenylacetylene and 3-hexyne failed to give cyclopropyl products
      under the same reaction conditions.

PMID- 16408988
TI  - Catalytic enantioselective Friedel-Crafts/Michael addition reactions of indoles
      to ethenetricarboxylates.
AB  - [reaction: see text] The Friedel-Crafts reaction is an important reaction for the
      formation of new C-C bonds. Recently, catalytic enantioselective Friedel-Crafts
      reaction of alkylidene malonates has been reported. However, the substituents in
      alkylidene malonates are limited. To explore new substituents such as carboxyl
      and carbonyl groups, catalytic enantioselective Friedel-Crafts reactions of
      reactive ethenetricarboxylates and acyl-substituted methylenemalonates 1 were
      investigated. The reaction of 1 with indoles in the presence of catalytic amounts
      of chiral bisoxazoline copper(II) complex (10%) in THF at room temperature gave
      alkylated products in high yields and up to 95% ee. The enantioselectivity can be
      explained by the secondary orbital interaction on approach of indole to the less
      hindered side of the 1-Cu(II)-ligand complex.

PMID- 16408989
TI  - Chromogenic oxazines for cyanide detection.
AB  - [reaction: see text] We have designed two heterocyclic compounds for the
      colorimetric detection of cyanide. The skeleton of both molecules fuses a
      benzooxazine ring to an indoline fragment and can be assembled efficiently in
      three synthetic steps starting from commercial precursors. The two compounds
      differ in the nature of the substituent on the carbon atom at the junction of the
      fused heterocycles, which can be either a methyl or a phenyl group. In the
      presence of cyanide, both molecules are converted quantitatively into cyanoamines
      with the concomitant appearance of an intense band in the visible region of the
      absorption spectrum. The developing absorption is a result of the opening of the
      benzooxazine ring with the formation of a 4-nitrophenylazophenolate chromophore.
      Nuclear magnetic resonance spectroscopy and X-ray crystallographic analyses
      demonstrate that the covalent attachment of a cyanide anion to the indoline
      fragment is responsible for these transformations. The chromogenic process is
      particularly fast for the methyl-substituted oxazine and can be exploited to
      detect micromolar concentrations of cyanide in water. Furthermore, the
      colorimetric response of this compound to cyanide does not suffer the
      interference of the halide anions, which instead are known to complicate the
      detection of cyanide in conventional sensing protocols. Thus, our mechanism and
      compounds for the colorimetric identification of cyanide can lead to the
      development of practical strategies for the convenient determination of this
      toxic anion in aqueous environments.

PMID- 16408990
TI  - Better understanding of the ring-cleavage process of cyanocyclopropyl anionic
      derivatives. A theoretical study based on the electron localization function.
AB  - [reaction: see text] Theoretical calculations at the B3LYP/6-31+G(d), MP2/6
      31+G(d), and G3(MP2) levels have been carried out to understand the alternative
      reaction pathways (the cyclopropyl ring cleavage (RC) and the retrocycloaddition
      reaction (rCA)) of a constrained tricyanocyclopropyl anionic derivative. The more
      energetically favorable path is found to be the RC process, a formally
      "forbidden" rearrangement (Leiviers, M.; Tam, I.; Groves, K.; Leung, D.; Xie, Y.;
      Breslow, R. Org. Lett. 2003, 5, 19, 3407) yielding an allylic anion system via a
      concerted transition structure, in agreement with experimental outcomes. rCA is
      more energetically favorable along a two-stage mechanism, via an intermediate,
      than a synchronous concerted process. By using isodesmic reactions, we have found
      that B3LYP presents limitations when it calculates carbon-carbon bond-breaking
      processes along the present rCA reaction. A detailed analysis of the nature of
      the topology of the reactive potential energy surface for the RC process points
      out the presence of a valley-ridge inflection point in the uphill part. An
      explanation for the low-energy barrier associated with RC is furnished on the
      analysis of the evolution of the twisting (dis-/conrotatory) motions of cyano
      substituents in the cyclopropyl ring as well as on the number and type of
      electron pairs provided by the electron localization function (ELF).

PMID- 16408991
TI  - Synthesis and ring size effect of macrocyclic ethynylhelicene oligomers.
AB  - [reaction: see text] The cyclization of acyclic ethynylhelicene oligomers with
      decyl 3,5-diiodobenzoate under optimized conditions gave the corresponding
      optically active [n+n]cycloalkynes (n = 4-8) in high yields. Their structures
      were compared in terms of ring size by using (1)H NMR, UV-vis, and CD
      spectroscopies and vapor pressure osmometry (VPO). The UV-vis spectra exhibited
      an increase in absorbance in proportion to n. In contrast, the CD spectra of the
      macrocycles exhibited a large ring size effect, comparable Deltaepsilon values
      despite the increase in n and temperature-dependent properties of the
      [8+8]cycloalkyne. It was concluded that [4+4]cycloalkyne, [5+5]cycloalkyne,
      [6+6]cycloalkyne, and [7+7]cycloalkyne have rigid structures, while
      [8+8]cycloalkyne has a flexible structure.

PMID- 16408992
TI  - Hydroxyl-terminated dendritic oligomers from bile acids: synthesis and
      properties.
AB  - [reaction: see text] The high reactivity of the chloroacetyl group has been
      exploited for the synthesis of bile acid based first and second generation
      dendrons with multiple hydroxyl groups. The synthesis involves only a few steps
      and avoids the use of protecting groups for the terminal hydroxyl groups. These
      dendritic structures with facially amphiphilic bile acid backbones on the
      periphery were able to solubilize cresol red, a hydrophilic dye, in a nonpolar
      solvent. HPLC analysis of the dendrons suggests that hydrophobicity increases
      with increase in oligomer size, but in each generation, the dendrons with a
      higher degree of branching are less hydrophobic.

PMID- 16408993
TI  - N-salicylideneanilines: tautomers for formation of hydrogen-bonded capsules,
      clefts, and chains.
AB  - [structure: see text] The synthesis, characterization, and solid-state structures
      of new salicylaldimines are reported. Bis(N-salicylideneaniline)s (BSANs) and
      tris(N-salicylideneaniline)s (TSANs) are sterically encumbered compounds
      featuring a central six-membered ring in the keto-enamine tautomer. When extended
      with additional functional groups, these molecules may form hydrogen-bonded
      capsules, clefts, and extended structures. A TSAN with N-(t)()BOC-o
      phenylenediamine groups has been structurally investigated. The complementary
      hydrogen-bonding motif in this molecule leads it to form dimers in solution and
      in the solid state. A BSAN with N-(t)()BOC-o-phenylenediamine substituents forms
      a hydrogen-bonded cleft in solution but forms an extended hydrogen-bonded ladder
      assembly of cofacial dimers in the solid state. When N-(t)()BOC-1,8
      naphthalenediamine was utilized to extend the cleft, an unusual perimidine
      structure was obtained with the central core in the enol tautomer. In addition,
      ab initio calculations have been used to support the assignment of the keto
      enamine or enol-imine tautomers of the BSANs and TSANs and to predict
      tautomerization in related BSANs and TSANs.

PMID- 16408994
TI  - Selective opening of ring C in the morphine skeleton by an unexpected cleavage of
      the C5-C6 bond in cycloadducts of thebaine and acyl nitroso compounds.
AB  - [reaction: see text] Acyl nitroso cycloadducts of the alkaloid thebaine undergo
      an unexpected cleavage of the C5-C6 bond when treated with 2 equiv of
      samarium(II) iodide in THF to give novel hexahydrobenzazocine products. A
      proposed mechanism for the transformation involves rearrangement of the initial
      radical anion.

PMID- 16408995
TI  - Synthesis, conformation, and stereodynamics of a salt of 2-{[2-(3,4
      dichlorophenyl)- ethyl]propylamino}-1-pyridin-3-ylethanol.
AB  - [reaction: see text] A novel synthetic route was developed for 2-{[2-(3,4
      dichlorophenyl)ethyl]propylamino}-1-pyridin-3-ylethanol (4). A dynamic process
      due to nitrogen inversion at the central amine nitrogen has been identified by
      NMR spectroscopy for the dihydrobromide salt of this compound. The conformational
      properties of the diastereomeric pair were determined by analysis of NOE
      connectivities and MO calculations.

PMID- 16408996
TI  - Singlet oxygen production in the reaction of superoxide with organic peroxides.
AB  - [reaction: see text] A selective chemiluminescent probe for singlet oxygen has
      been employed to detect and quantify singlet oxygen in the reactions of
      superoxide with organic peroxides. The production of singlet oxygen has been
      quantified in the reaction of superoxide with benzoyl peroxide (BP). No singlet
      oxygen was detected in the reactions of superoxide with cumyl peroxide, tert
      butyl peroxide, or tert-butyl hydroperoxide. On the basis of these results and on
      the temperature dependence of the reaction, we proposed a mechanism for singlet
      oxygen formation in the reaction of superoxide with BP.

PMID- 16408997
TI  - Practical and simple synthesis of substituted quinolines by an HCl-DMSO system on
      a large scale: remarkable effect of the chloride ion.
AB  - [reaction: see text] A variety of substituted quinolines are synthesized from
      imines and enolizable carbonyl compounds under aerobic conditions, in which only
      water is a byproduct. In DMSO, a catalytic amount of HCl activates carbonyl
      compounds quite effectively to give the quinolines. A simple and practical
      procedure is demonstrated on a large scale.

PMID- 16408998
TI  - Acetyltrimethylsilane: a novel reagent for the transformation of 2H-pyran-2-ones
      to unsymmetrical biaryls.
AB  - [reaction: see text] An expeditious synthesis of unsymmetrical biaryls
      functionalized with electron-withdrawing or -donating substituents is described
      and illustrated by carbanion-induced ring transformation of 2H-pyran-2-one using
      acetyltrimethylsilane (ATMS) as a novel reagent in good yield. The novelty of the
      reaction lies in the creation of an aromatic ring from 2H-pyran-2-ones via two
      carbon insertion from ATMS used as a source of carbanion.

PMID- 16408999
TI  - Synthesis of 1,3-dithiin dithioortho esters from the reaction of Fischer carbenes
      and 3H-1,2-dithiole-3-thiones.
AB  - [reaction: see text] Tricyclic 4-ethyl-5-thioxo-3H,5H-bis[1,2]dithiolo[3,4-d][4,3
      b]pyrrol-3-one and monocyclic 3H-1,2-dithiole-3-thione derivatives reacted with
      Fischer carbene complexes, giving 1,3-dithiin dithioortho esters through
      insertion of the carbenic carbon into the S-S bond next to the thiocarbonyl
      function of the substrate.

PMID- 16409000
TI  - Facile peripheral modification of N-confused porphyrin.
AB  - [reaction: see text] An improved methodology for the N-alkylation of the
      porphyrin isomer N-confused porphyrin is presented. The combination of polar
      solvent conditions and the use of the base Cs2CO3 affords externally modified
      products in high yield without separation difficulties and without the use of
      large excesses of alkylating reagent. The further transformation and metalation
      of these products provides opportunities for the construction of metalloenzyme
      model complexes, peptide adducts, and chromophore assemblies.

PMID- 16409001
TI  - A versatile method for the synthesis of 3-alkoxycarbonyl beta-lactam derivatives.
AB  - [reaction: see text] Ketene-imine cycloaddition reactions (the Staudinger
      reaction) of ethoxycarbonyl(phenylthio)ketene with various imines and subsequent
      desulfurization reactions were employed to synthesize 3-ethoxycarbonyl beta
      lactam derivatives. The results indicate that the current approach provides a
      convenient, mild, and versatile method for synthesizing a variety of 3
      alkoxycarbonyl trans-beta-lactam derivatives with good to excellent yields and
      diastereoselectivities.

PMID- 16409002
TI  - Some new routes for the preparation of 3-amino-2-phenyl-4(1H)-quinolinones from
      anthranilamides.
AB  - [reaction: see text] Several new routes for the preparation of 3-amino-2-phenyl-4
      1(H)-quinolinone 7a are compared. The most efficient is based on the cyclization
      of phenacyl anthranilamide 2a in the presence of (poly)phosphoric acid. The
      mechanisms of the rearrangements involved are discussed on the basis of the
      structures of isolated heterocyclic intermediates. The best methodology for the
      preparation of the title compound 7a was verified, and 10 other quinolinones 7
      were prepared.

PMID- 16409003
TI  - Efficient synthesis of N-methoxyindoles via alkylative cycloaddition of
      nitrosoarenes with alkynes.
AB  - [reaction: see text] N-Methoxyindoles are produced in moderate to excellent
      yields from the reaction between nitrosoarenes and alkynes in the presence of
      K2CO3/(CH3)2SO4. Terminal alkynes with conjugating substituents afford 3
      substituted N-methoxyindoles exclusively. The analogous reactions with methyl
      propiolate provide a one-step preparation of phytoalexin analogues from Wasabi.

PMID- 16409004
TI  - Practical method for transforming alkynes into alpha-diketones.
AB  - [reaction: see text] Oxidation of alkynes to alpha-dicarbonyl derivatives through
      a convenient one-pot procedure via a Bronsted acid-promoted "hydration" and a
      DMSO-based oxidation sequence has been achieved in high yields. The scope and
      limitations of the reaction have also been investigated.

PMID- 16409005
TI  - Reaction of an Aza[60]fullerene radical with diphenylmethanes and fluorenes: a
      mechanistic approach.
AB  - [reaction: see text] The mechanism of the reaction of azafullerene radical
      C(59)N(*) with diphenylmethane and 9-methyl-9H-fluorene has been investigated.
      The primary and secondary kinetic isotope effects provide strong evidence for a
      stepwise mechanism in which the hydrogen-atom abstraction is the rate-determining
      step.

PMID- 16409006
TI  - Asymmetric synthesis of functionalized diarylmethanols catalyzed by a new gamma
      amino thiol.
AB  - [reaction: see text] A mild asymmetric arylation of aromatic aldehydes catalyzed
      by gamma-amino thiol 5 gave the corresponding diarylmethanols with 95 to >99.5%
      ee.

PMID- 16409007
TI  - An efficient synthesis of the natural tetrahydrofuran pachastrissamine starting
      from D-ribo-phytosphingosine.
AB  - [reaction: see text] The natural product pachastrissamine, an
      anhydrophytosphingosine derivative isolated from various sponges and endowed with
      cytotoxic activity against several human carcinoma cell lines, was synthesized in
      three steps and with 72% overall yield from d-ribo-phytosphingosine.

PMID- 16409009
TI  - Pentiptycene chemistry: new pentiptycene building blocks derived from
      pentiptycene quinones.
AB  - [reaction: see text] An efficient synthesis of new middle-ring disubstituted
      pentiptycenes from pentiptycene quinone is reported. One of the substituents is a
      bromo, iodo, amino, nitro, cyano, or formyl group and the other is a hydroxy or
      alkoxy group. These disubstituted pentiptycenes are potential building blocks for
      constructing novel pentiptycene-incorporated systems.

PMID- 16409008
TI  - Highly diastereoselective catalytic Meerwein-Ponndorf-Verley reductions.
AB  - [reaction: see text] Very practical synthesis of ephedrine analogues in high
      yields and enantiopurity was realized by a highly diastereoselective Meerwein
      Ponndorf-Verley (MPV) reduction of protected alpha-amino aromatic ketones using
      catalytic aluminum isopropoxide. The high anti selectivity resulted from the
      chelation of the nitrogen anion to the aluminum. In contrast, high syn
      selectivity was obtained with alpha-alkoxy ketones and other compounds via Felkin
      Ahn control.

PMID- 16409010
TI  - 9-(4-Bromophenyl)-9-fluorenyl as a safety-catch nitrogen protecting group.
AB  - [reaction: see text] The 9-(4-bromophenyl)-9-fluorenyl (BrPhF) group has been
      developed as a novel safety-catch amine protection. This relatively acid-stable
      protecting group can be successfully activated by palladium-catalyzed cross
      coupling reaction of the aryl bromide with morpholine and then cleaved
      effectively under mild conditions using dichloroacetic acid and triethylsilane.
      Complementary conditions are reported for selective removal of the BrPhF group in
      the presence of tert-butyl esters and carbamates as well as deprotection of tert
      butyl esters and carbamates in the presence of BrPhF amines.

PMID- 16409012
TI  - Managing asthma in expectant mothers.
AB  - Pregnancy does not appear to have a consistent effect on the frequency or
      severity of asthma. The most common cause of worsening asthma in pregnancy is
      likely to be noncompliance with medication. Emphasizing to the patient in advance
      that fetal well-being is dependent on maternal well-being may help prevent
      this.In general, well controlled asthma is not associated with a higher risk of
      adverse pregnancy outcomes. Essential to successful asthma management is patient
      education that helps to ensure effective medication use, avoidance of triggers,
      and prompt treatment. This education should include measurement of peak
      expiratory flow rate and a written asthma action plan. Most of the medications
      that are used to control asthma in the general population can be safely used in
      pregnant women. Inhaled beta-adrenoceptor agonists (beta-agonists), cromolyn
      sodium (sodium cromoglycate), and inhaled and systemic corticosteroids all appear
      to be very well tolerated by the fetus. Budesonide and beclomethasone should be
      considered as the preferred inhaled corticosteroids for the treatment of asthma
      in pregnancy. Use of the leukotriene receptor antagonists zafirlukast and
      montelukast in pregnancy is probably safe but should be limited to special
      circumstances, where they are viewed essential for asthma control. Zileuton
      should not be used in pregnancy.Acute asthma exacerbations in pregnant women
      should be treated in a similar manner to that in non-pregnant patients. Maternal
      blood glucose levels should be monitored periodically in pregnant women receiving
      systemic corticosteroids because of the deleterious effects of hyperglycemia upon
      embryos and fetuses. During pregnancy, maternal arterial oxygen saturations
      should be kept above 95% if possible for fetal well-being. Ambulatory oxygenation
      should be checked prior to discharge to ensure that women do not desaturate with
      their daily activities.Acute exacerbations of asthma during labor and delivery
      are rare. Dinoprost, ergometrine, and other ergot derivatives can cause severe
      bronchospasm, especially when used in combination with general anesthesia, and
      should be avoided in asthmatic patients. Pregnant women who have been treated
      with corticosteroids in the past year may require stress-dose corticosteroids
      during labor and delivery. Most asthma medications, including oral prednisone,
      are considered compatible with breast-feeding.

PMID- 16409013
TI  - Nosocomial pneumonia : rationalizing the approach to empirical therapy.
AB  - Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable
      morbidity and mortality. It is the second most common nosocomial infection and
      the leading cause of death from hospital-acquired infections. In 1996 the
      American Thoracic Society (ATS) published guidelines for empirical therapy of
      HAP. This review focuses on the literature that has appeared since the ATS
      statement. Early diagnosis of HAP and its etiology is crucial in guiding
      empirical therapy. Since 1996, it has become clear that differentiating mere
      colonization from etiologic pathogens infecting the lower respiratory tract is
      best achieved by employing bronchoalveolar lavage (BAL) or protected specimen
      brush (PSB) in combination with quantitative culture and detection of
      intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB
      in combination with quantitative culture provide a good alternative in patients
      suspected of ventilator-associated pneumonia. Since culture results take 2-3
      days, initial therapy of HAP is by definition empirical. Epidemiologic studies
      have identified the most frequently involved pathogens: Enterobacteriaceae,
      Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus ('core
      pathogens'). Empirical therapy covering only the 'core pathogens' will suffice in
      patients without risk factors for resistant microorganisms. Studies that have
      appeared since the ATS statement issued in 1996, demonstrate several new risk
      factors for HAP with multiresistant pathogens. In patients with risk factors,
      empirical therapy should consist of antibacterials with a broader spectrum. The
      most important risk factors for resistant microorganisms are late onset of HAP
      (>/=5 days after admission), recent use of antibacterial therapy, and mechanical
      ventilation. Multiresistant bacteria of specific interest are methicillin
      resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus
      baumannii, Stenotrophomonas maltophilia and extended-spectrum beta-lactamase
      (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific
      susceptibility pattern, demanding appropriate antibacterial treatment. To further
      improve outcomes, specific therapeutic options for multiresistant pathogens and
      pharmacological factors are discussed. Antibacterials developed since 1996 or
      antibacterials with renewed interest (linezolid, quinupristin/dalfopristin,
      teicoplanin, meropenem, new fluoroquinolones, and fourth-generation
      cephalosporins) are discussed in the light of developing resistance.Since the ATS
      statement, many reports have shown increasing incidences of resistant
      microorganisms. Therefore, one of the most important conclusions from this review
      is that empirical therapy for HAP should not be based on general guidelines
      alone, but that local epidemiology should be taken into account and used in the
      formulation of local guidelines.

PMID- 16409014
TI  - New strategies for the treatment of pulmonary hypertension in sickle cell disease
      : the rationale for arginine therapy.
AB  - Nitric oxide (NO) is inactivated in sickle cell disease (SCD), while
      bioavailability of arginine, the substrate for NO synthesis, is diminished.
      Impaired NO bioavailability represents the central feature of endothelial
      dysfunction, and is a key factor in the pathophysiology of SCD. Inactivation of
      NO correlates with the hemolytic rate and is associated with erythrocyte release
      of cell-free hemoglobin and arginase during hemolysis. Accelerated consumption of
      NO is enhanced further by the inflammatory environment of oxidative stress that
      exists in SCD. Based upon its critical role in mediating vasodilation and cell
      growth, decreased NO bioavailability has also been implicated in the pathogenesis
      of pulmonary arterial hypertension (PHT). Secondary PHT is a common life
      threatening complication of SCD that also occurs in most hereditary and chronic
      hemolytic disorders. Aberrant arginine metabolism contributes to endothelial
      dysfunction and PHT in SCD, and is strongly associated with prospective patient
      mortality. The central mechanism responsible for this metabolic disorder is
      enhanced arginine turnover, occurring secondary to enhanced plasma arginase
      activity. This is consistent with a growing appreciation of the role of excessive
      arginase activity in human diseases, including asthma and PHT.
      Decompartmentalization of hemoglobin into plasma consumes endothelial NO and thus
      drives a metabolic requirement for arginine, whose bioavailability is further
      limited by arginase activity. New treatments aimed at maximizing both arginine
      and NO bioavailability through arginase inhibition, suppression of hemolytic
      rate, or oral arginine supplementation may represent novel therapeutic
      strategies.

PMID- 16409015
TI  - Antioxidant strategies in respiratory medicine.
AB  - Pulmonary oxidant stress plays an important pathogenetic role in disease
      conditions including acute lung injury/adult respiratory distress syndrome
      (ALI/ARDS), hyperoxia, ischemia-reperfusion, sepsis, radiation injury, lung
      transplantation, COPD, and inflammation. Reactive oxygen species (ROS), released
      from activated macrophages and leukocytes or formed in the pulmonary epithelial
      and endothelial cells, damage the lungs and initiate cascades of pro-inflammatory
      reactions propagating pulmonary and systemic stress. Diverse molecules including
      small organic compounds (e.g. gluthatione, tocopherol (vitamin E), flavonoids)
      serve as natural antioxidants that reduce oxidized cellular components, decompose
      ROS and detoxify toxic oxidation products. Antioxidant enzymes can either
      facilitate these antioxidant reactions (e.g. peroxidases using glutathione as a
      reducing agent) or directly decompose ROS (e.g. superoxide dismutases [SOD] and
      catalase). Many antioxidant agents are being tested for treatment of pulmonary
      oxidant stress. The administration of small antioxidants via the oral,
      intratracheal and vascular routes for the treatment of short- and long-term
      oxidant stress showed rather modest protective effects in animal and human
      studies. Intratracheal and intravascular administration of antioxidant enzymes
      are being currently tested for the treatment of acute oxidant stress. For
      example, intratracheal administration of recombinant human SOD is protective in
      premature infants exposed to hyperoxia. However, animal and human studies show
      that more effective delivery of drugs to cells experiencing oxidant stress is
      needed to improve protection. Diverse delivery systems for antioxidants including
      liposomes, chemical modifications (e.g. attachment of masking pegylated [PEG]
      groups) and coupling to affinity carriers (e.g. antibodies against cellular
      adhesion molecules) are being employed and currently tested, mostly in animal
      and, to a limited extent, in humans, for the treatment of oxidant stress. Further
      studies are needed, however, in order to develop and establish effective
      applications of pulmonary antioxidant interventions useful in clinical practice.
      Although beyond the scope of this review, antioxidant gene therapies may
      eventually provide a strategy for the management of subacute and chronic
      pulmonary oxidant stress.

PMID- 16409016
TI  - A full dimensional time-dependent wave packet study for the H4 four-center,
      collision induced dissociation, and single exchange reactions: reaction
      probabilities for J=0.
AB  - A time-dependent initial state selected wave packet method has been developed to
      study the H2(v(1)=10-11,j1=0)+H2'(v2=0,j2=0)-->HH'+HH' four-center (4C) reaction,
      and two other competing reactions: the H2+H2'-->H+H+H2' collision induced
      dissociation (CID) and the H2+H2'-->H+HH'+H' single exchange (SE) reaction, in
      full six dimensions. Initial state-specific total reaction probabilities for
      these three competing reactions are presented for total angular momentum J=0 and
      the effects of reagent vibration on reactions are examined. It is found that (a)
      the CID process is the dominant process over the whole energy range considered in
      this study, but the 4C and SE processes also have non-negligible probabilities;
      (b) the SE process has a lower threshold energy than the 4C process, but the SE
      probability increases slower than the 4C probability as collision energy
      increases; (c) the vibrational excitation of H2(v1) is much more efficient than
      translational motion for promoting these processes, in particular to the CID
      process.

PMID- 16409017
TI  - State-resolved reactive scattering by slice imaging: a new view of the Cl+C2H6
      reaction.
AB  - We present state-resolved crossed beam scattering results for the reaction
      Cl+C2H6-->HCl+C2H5, obtained using direct current slice imaging. The HCl
      (v=0,J=2) image, recorded at a collision energy of 6.7+/-0.6 kcalmol, shows
      strongly coupled angular and translational energy distributions revealing
      features of the reaction not seen in previous studies. The overall distribution
      is mainly forward scattered with respect to the Cl beam, with a translational
      energy distribution peaking near the collision energy. However, there is a
      substantial backscattered contribution that is very different. It shows a sharp
      peak at 8.0 kcalmol, but extends to much lower energy, implying substantial
      internal excitation in the ethyl radical coproduct. These results provide new
      insight into the reaction, and they are considered in terms of alternative models
      of the dynamics. This work represents the first genuine crossed-beam study in
      which a product other than the methyl radical was detected with quantum state
      specificity, showing the promise of the approach generally for high resolution
      state-resolved reactive scattering.

PMID- 16409018
TI  - Additions to the class of symmetric-antisymmetric multiwavelets: derivation and
      use as quantum basis functions.
AB  - Multiwavelet bases have been shown recently to apply to a variety of quantum
      problems. There are, however, only a few multiwavelet families that have been
      defined to date. Chui-Lian-type symmetric and antisymmetric multiwavelets are
      derived here that equal and exceed the polynomial interpolating power of
      previously available examples. Adaptations to domain edges are made with a view
      to use in curvilinear coordinate molecular calculations. The new highest-order
      multiwavelet family is shown to provide uniformly better performance for (i)
      basis representation of terms such as 1r(2) in near approach to the singularity
      at r=0 and (ii) eigenvalue calculation of a bending Hamiltonian taken from a
      curvilinear model of the ground-state vibrations of nitrosyl chloride.

PMID- 16409019
TI  - Coupled-perturbed density-matrix functional theory equations. Application to
      static polarizabilities.
AB  - Starting from the variational equations for the natural occupation numbers and
      the recently proposed eigenequations for the natural spin-orbitals, we derive
      coupled-perturbed density-matrix equations that furnish a linear response of the
      one-electron reduced density matrix to a static perturbation when the total
      energy is a functional of the one-electron reduced density matrix. Cases when
      some occupation numbers achieve exactly 0 or 1 or when the total number of the
      particles in a system is not preserved are taken into consideration. The scheme
      is applied to computing static polarizabilities from two simple density-matrix
      functionals. The behavior of the functionals is erratic and they provide only
      little or no improvement over the coupled-perturbed Hartree-Fock results.

PMID- 16409020
TI  - The boundary fluctuation theory of transport coefficients in the linear-response
      limit.
AB  - In this paper we present, for the first time, a linear-response theory of
      transport coefficients-shear viscosity and thermal conductivity-involving
      thermal, as opposed to mechanical, fields. The theory involves the explicit
      treatment of the boundaries and the constraints that are applied to them.
      Expressions for the shear viscosity and thermal conductivity are obtained in
      terms of the fluctuations at the boundaries of the variable conjugate to that
      which is constrained. We explain how the choice of ensemble, as defined by the
      boundary constraints, determines the form in which the transport coefficients are
      evaluated.

PMID- 16409022
TI  - On the emergence of molecular structure from atomic shape in the 1/r2 harmonium
      model.
AB  - The formal similarity of the three-body Hamiltonians for helium and the hydrogen
      molecule ion is used to demonstrate the unfolding of a rotating dumbbell-like
      proton distribution from a (1s)2-type electron distribution by smooth variation
      of the particles' masses in the 1/r2 harmonium model. The 1/r2 harmonium is an
      exactly solvable modification of the harmonium model (also known as Hooke's law
      atom) where the attraction between different particles is harmonic and the
      repulsion between the two equal particles is given by a 1/r2 potential. The
      dumbbell-like molecular structure appears as an expression of increasing spatial
      correlation due to increasing mass. It gradually appears in the one-density
      distribution of the two equal particles if their mass exceeds a critical value
      depending on the mass of the third particle. For large mass of the equal
      particles, their one-density distribution approaches an asymptotic form derived
      from the Born-Oppenheimer treatment of H2+ in the 1/r2 harmonium model. Below the
      critical value, the one density is a spherical, Gaussian-type atomic density
      distribution with a maximum at the center of mass. The topological transition at
      the critical value separates molecular structure and atomic shape as two
      qualitatively different manifestations of spatial structure.

PMID- 16409021
TI  - Exchange-hole dipole moment and the dispersion interaction: high-order dispersion
      coefficients.
AB  - In recent publications [A. D. Becke and E. R. Johnson, J. Chem. Phys. 122, 154104
      (2005); E. R. Johnson and A. D. Becke 123, 024101 (2005)] we have demonstrated
      that the position-dependent dipole moment of the exchange hole can be used to
      generate dispersion interactions between closed-shell systems. Remarkably
      accurate C6 coefficients and intermolecular potential-energy surfaces can be
      obtained from Hartree-Fock occupied orbitals and polarizability data alone. In
      the present work, our model is extended to predict C8 and C10 coefficients as
      well. These higher-order coefficients are obtained as easily as C6 and with
      comparable accuracy.

PMID- 16409023
TI  - Analytical calculations of molecular integrals for multielectron R-matrix
      methods.
AB  - Closed-form analytical expressions for one- and two-electron integrals between
      Cartesian Gaussians over a finite spherical region of space are developed for use
      in ab initio molecular scattering calculations. In contrast with some previous
      approaches, the necessary integrals are formulated solely in terms of finite
      summations involving standard functions. The molecular integrals evaluated over
      the finite region of space are computed by subtracting the contributions outside
      the region from the integrals over all space. The latter integrals can be
      efficiently and accurately obtained from existing bound-state algorithms. Our
      approach incorporates molecular scattering calculations into current quantum
      chemistry programs and facilitates the unification of bound- and continuum-state
      calculations for both diatomic and polyatomic molecules. Multidimensional Monte
      Carlo numerical integrations validate the high accuracy of our closed form
      results for the two-electron integrals.

PMID- 16409024
TI  - Scalable implementation of analytic gradients for second-order Z-averaged
      perturbation theory using the distributed data interface.
AB  - The analytic gradient expression for second-order Z-averaged perturbation theory
      is revised and its parallel implementation is described in detail. The
      distributed data interface is used to access molecular-orbital integral arrays
      stored in distributed memory. The algorithm is designed to maximize the use of
      local data and reduce communication costs. The iterative solution and the
      preconditioner used to induce the convergence of the coupled-perturbed Hartree
      Fock equations are presented. Several illustrative timing examples are discussed.

PMID- 16409025
TI  - On the relation between quantum lifetimes and classical stability for the systems
      with a saddle-type potential.
AB  - Relations between quantum-mechanical and classical properties of open systems
      with a saddle-type potential, for which at a given energy only one unstable
      periodic orbit exists, are studied. By considering the convergence of the
      Gutzwiller trace formula [J. Math. Phys. 12, 343 (1971)] it is confirmed that
      both for homogeneous and inhomogeneous potentials the poles of the formula are
      located below the real energy axis, i.e., these kind of potentials do not support
      bound states, in general. Within the harmonic approximation the widths of
      resonant (transition) states are proportional to the values of Lyapunov exponent
      of the single periodic orbit calculated at the energies which are equal to the
      resonance positions. The accuracy of the semiclassical relation is discussed and
      demonstrated for several examples.

PMID- 16409026
TI  - Irreducible correlation functions of the S matrix in the coordinate
      representation: application in calculating Lorentzian half-widths and shifts.
AB  - By introducing the coordinate representation, the derivation of the perturbation
      expansion of the Liouville S matrix is formulated in terms of classically behaved
      autocorrelation functions. Because these functions are characterized by a pair of
      irreducible tensors, their number is limited to a few. They represent how the
      overlaps of the potential components change with a time displacement, and under
      normal conditions, their magnitudes decrease by several orders of magnitude when
      the displacement reaches several picoseconds. The correlation functions contain
      all dynamical information of the collision processes necessary in calculating
      half-widths and shifts and can be easily derived with high accuracy. Their well
      behaved profiles, especially the rapid decrease of the magnitude, enables one to
      transform easily the dynamical information contained in them from the time domain
      to the frequency domain. More specifically, because these correlation functions
      are well time limited, their continuous Fourier transforms should be band
      limited. Then, the latter can be accurately replaced by discrete Fourier
      transforms and calculated with a standard fast Fourier transform method. Besides,
      one can easily calculate their Cauchy principal integrations and derive all
      functions necessary in calculating half-widths and shifts. A great advantage
      resulting from introducing the coordinate representation and choosing the
      correlation functions as the starting point is that one is able to calculate the
      half-widths and shifts with high accuracy, no matter how complicated the
      potential models are and no matter what kind of trajectories are chosen. In any
      case, the convergence of the calculated results is always guaranteed. As a
      result, with this new method, one can remove some uncertainties incorporated in
      the current width and shift studies. As a test, we present calculated Raman Q
      linewidths for the N2-N2 pair based on several trajectories, including the more
      accurate "exact" ones. Finally, by using this new method as a benchmark, we have
      carried out convergence checks for calculated values based on usual methods and
      have found that some results in the literature are not converged.

PMID- 16409027
TI  - Finite basis representations with nondirect product basis functions having
      structure similar to that of spherical harmonics.
AB  - The currently most efficient finite basis representation (FBR) method [Corey et
      al., in Numerical Grid Methods and Their Applications to Schrodinger Equation,
      NATO ASI Series C, edited by C. Cerjan (Kluwer Academic, New York, 1993), Vol.
      412, p. 1; Bramley et al., J. Chem. Phys. 100, 6175 (1994)] designed specifically
      to deal with nondirect product bases of structures phi(n) (l)(s)f(l)(u), chi(m)
      (l)(t)phi(n) (l)(s)f(l)(u), etc., employs very special l-independent grids and
      results in a symmetric FBR. While highly efficient, this method is not general
      enough. For instance, it cannot deal with nondirect product bases of the above
      structure efficiently if the functions phi(n) (l)(s) [and/or chi(m) (l)(t)] are
      discrete variable representation (DVR) functions of the infinite type. The
      optimal-generalized FBR(DVR) method [V. Szalay, J. Chem. Phys. 105, 6940 (1996)]
      is designed to deal with general, i.e., direct and/or nondirect product, bases
      and grids. This robust method, however, is too general, and its direct
      application can result in inefficient computer codes [Czako et al., J. Chem.
      Phys. 122, 024101 (2005)]. It is shown here how the optimal-generalized FBR
      method can be simplified in the case of nondirect product bases of structures
      phi(n) (l)(s)f(l)(u), chi(m) (l)(t)phi(n) (l)(s)f(l)(u), etc. As a result the
      commonly used symmetric FBR is recovered and simplified nonsymmetric FBRs
      utilizing very special l-dependent grids are obtained. The nonsymmetric FBRs are
      more general than the symmetric FBR in that they can be employed efficiently even
      when the functions phi(n) (l)(s) [and/or chi(m) (l)(t)] are DVR functions of the
      infinite type. Arithmetic operation counts and a simple numerical example
      presented show unambiguously that setting up the Hamiltonian matrix requires
      significantly less computer time when using one of the proposed nonsymmetric FBRs
      than that in the symmetric FBR. Therefore, application of this nonsymmetric FBR
      is more efficient than that of the symmetric FBR when one wants to diagonalize
      the Hamiltonian matrix either by a direct or via a basis-set contraction method.
      Enormous decrease of computer time can be achieved, with respect to a direct
      application of the optimal-generalized FBR, by employing one of the simplified
      nonsymmetric FBRs as is demonstrated in noniterative calculations of the low
      lying vibrational energy levels of the H3+ molecular ion. The arithmetic
      operation counts of the Hamiltonian matrix vector products and the properties of
      a recently developed diagonalization method [Andreozzi et al., J. Phys. A Math.
      Gen. 35, L61 (2002)] suggest that the nonsymmetric FBR applied along with this
      particular diagonalization method is suitable to large scale iterative
      calculations. Whether or not the nonsymmetric FBR is competitive with the
      symmetric FBR in large-scale iterative calculations still has to be investigated
      numerically.

PMID- 16409028
TI  - Quantum control of molecular vibrational and rotational excitations in a
      homonuclear diatomic molecule: a full three-dimensional treatment with
      polarization forces.
AB  - The optimal control of the vibrational excitation of the hydrogen molecule
      [Balint-Kurti et al., J. Chem. Phys. 122, 084110 (2005)] utilizing polarization
      forces is extended to three dimensions. The polarizability of the molecule, to
      first and higher orders, is accounted for using explicit ab initio calculations
      of the molecular electronic energy in the presence of an electric field. Optimal
      control theory is then used to design infrared laser pulses that selectively
      excite the molecule to preselected vibrational-rotational states. The amplitude
      of the electric field of the optimized pulses is restricted so that there is no
      significant ionization during the process, and a new frequency sifting method is
      used to simplify the frequency spectrum of the pulse. The frequency spectra of
      the optimized laser pulses for processes involving rotational excitation are more
      complex than those relating to processes involving only vibrational excitation.

PMID- 16409029
TI  - A fragment molecular-orbital-multicomponent molecular-orbital method for
      analyzing HD isotope effects in large molecules.
AB  - We have developed a fragment molecular orbital (FMO)-multi-component MO (MC_MO)
      method to analyze isotope effect due to differences between the quantum effects
      of protons and deuterons for large molecules such as proteins and DNA. The FMO
      MC_MO method enables the determination of both the electronic and the protonic
      (deuteronic) wave functions simultaneously, and can directly express isotope
      effects, including coupling effects between nuclei and electrons. In our
      calculations of two polyglycines, which serve as prototypes for biological
      molecules, by this method, we clearly observed the geometrical relaxation induced
      by the HD isotope effect in the intramolecular hydrogen bonding portions of the
      molecules. The HD isotope effect on the interfragment interaction energy,
      including that of the hydrogen bonding parts, was also demonstrated: the hydrogen
      bond was weakened by replacement of hydrogen with deuterium. We also developed
      electrostatic potential approximations for use in the FMO-MC_MO calculations, and
      the accuracy of the energy differences induced by the isotope effect was
      independent of the approximation level of the FMO-MC_MO. Our results confirmed
      that the FMO-MC_MO method is a powerful tool for the detailed analysis of changes
      in hydrogen bonding and interaction energies induced by the HD isotope effect for
      large biological molecules.

PMID- 16409030
TI  - Microwave and ab initio studies of the Xe-CH4 van der Waals complex.
AB  - An ab initio potential-energy surface of the Xe-CH4 van der Waals complex was
      constructed at the coupled cluster level of theory with single, double, and
      perturbatively included triple excitations. The recently developed small-core
      pseudopotential and augmented correlation-consistent polarized valence quadruple
      zeta basis set was used for the xenon atom and Dunning's augmented correlation
      consistent polarized valence triple-zeta basis set for the other atoms. The basis
      sets were supplemented with bond functions. Dipole moments were also calculated
      at various configurations. Rotational spectra of the Xe-CH4 van der Waals complex
      were recorded using a pulsed-nozzle Fourier transform microwave spectrometer. The
      isotopomers studied include those of CH4,13CH4,CD4,CH3D, and CHD3 with the five
      most abundant Xe isotopes. Transitions within three internal rotor states,
      namely, the j=0,K=0; j=1,K=0; and j=2,K=1 states, were observed and assigned.
      Nuclear quadrupole hyperfine structures due to the presence of 131Xe(I=3/2) were
      detected and analyzed. It was found that the j=1,K=0 state is perturbed by a
      Coriolis interaction with a nearby j=1,K=1 state. For isotopomers containing CH3D
      and CHD3, the j=2 states are no longer metastable and could not be observed. The
      spectroscopic results were used to derive structural and dynamical information of
      the Xe-CH4 complex.

PMID- 16409032
TI  - Correlated product distributions from ketene dissociation measured by dc sliced
      ion imaging.
AB  - Speed distributions of spectroscopically selected CO photoproducts of 308 nm
      ketene photodissociation have been measured by dc sliced ion imaging. Structured
      speed distributions are observed that match the clumps and gaps in the singlet
      CH2 rotational density of states. The effects of finite time gates in sliced ion
      imaging are important for the accurate treatment of quasicontinuous velocity
      distributions extending into the thickly sliced and fully projected regime, and
      an inversion algorithm has been implemented for the special case of isotropic
      fragmentation. With accurate velocity calibration and careful treatment of the
      velocity resolution, the new method allows us to characterize the coincident
      rotational state distribution of CH2 states as a smoothly varying deviation from
      an unbiased phase space theory (PST) limit, similar to a linear-surprisal
      analysis. High-energy rotational states of CH2 are underrepresented compared to
      PST in coincidence with all detected CO rotational states. There is no evidence
      for suppression of the fastest channels, as had been reported in two previous
      studies of this system by other techniques. The relative contributions of ground
      and first vibrationally excited singlet CH2 states in coincidence with selected
      rotational states of CO (upsilon=0) are well resolved and in remarkably good
      agreement with PST, despite large deviations from the PST rotational
      distributions in the CH2 fragments. At 308 nm, the singlet CH2 (upsilon2=0) and
      (upsilon2=1) channels are 2350 and 1000 cm(-1) above their respective thresholds.
      The observed vibrational branching is consistent with saturation at increasing
      energies of the energy-dependent suppression of rates with respect to the PST
      limit, attributed to a tightening variational transition state.

PMID- 16409033
TI  - First-principles calculation of geometry and anharmonic vibrational spectra of
      thioformamide and thioformamide-d2.
AB  - The equilibrium geometry of thioformamide HCSNH2 has been determined at the MP2
      and CCSD(T) electron correlation levels under C(s) symmetry constraints using
      triple-zeta basis sets up to cc-pVTZ. All optimized planar structures are true
      minima on the potential-energy surface and are characterized by the C-N bond
      length within 1.353-1.343 A, C-S distances of 1.656-1.628 A, and NCS angle
      between 125.7 degrees and 125.9 degrees . The wave number of the NH2 out-of-plane
      wagging mode computed in the harmonic approximation shows stronger dependence on
      the basis set rather than the electron correlation level and varies from 85.9 cm(
      1) at CCSD(T)cc-pVDZ level to 335 cm(-1) at MP2/aug-cc-pVTZ level. Anharmonic
      vibrational spectra of HCSNH2 and HCSND2 have been determined directly from the
      potential-energy surfaces computed at MP2 level in triple-zeta valence
      (TZV)(2df,2p) and TZV+(2df,2p) basis sets using vibrational self-consistent-field
      (VSCF) and correlation-corrected VSCF (CC-VSCF) methods. CC-VSCF wave numbers of
      fundamental, first overtone, and most intense combination transitions are
      reported for thioformamide and those of fundamentals for thioformamide-d2. The
      NH2 wagging (nu12) mode is strongly anharmonic and its fundamentals have been
      computed at 406.9 cm(-1) [TZV(2df,2p)] and 399.5 cm(-1) [TZV+(2df,2p)], which is
      remarkably close to the experimental energy of 393 cm(-1). Anharmonically
      computed fundamentals of this mode in thioformamide-d2, 299.7 cm(-1)
      [TZV(2df,2p)] and 299.6 cm(-1) [TZV+(2df,2p)], are only approximately 7 cm(-1)
      higher than the transition energy (293 cm(-1)) observed in the gas phase spectrum
      of HCSND2. The first overtone of the NH2 wagging mode of thioformamide (nu12
      (02)) has been calculated by CC-VSCF procedure at 830.8 cm(-1) [TZV(2df,2p)] and
      880.0 cm(-1) [TZV+(2df,2p)], which implies "negative" (nu12 (02)>2*nu12 (01))
      anharmonicity of this mode.

PMID- 16409031
TI  - On the effect of a radiation field in modifying the intermolecular interaction
      between two chiral molecules.
AB  - The change in the mutual energy of interaction between a pair of chiral molecules
      coupled via the exchange of a single virtual photon and in the presence of an
      electromagnetic field is calculated using nonrelativistic quantum
      electrodynamics. The particular viewpoint adopted is one that has an intuitive
      physical appeal and resembles a classical treatment. It involves the coupling of
      electric and magnetic dipole moments induced at each center by the incident
      radiation field to the resonant dipole-dipole interaction tensor. The energy
      shift is evaluated for fixed as well as random orientations of the molecular pair
      with respect to the direction of propagation of the field. A complete
      polarization analysis is carried out for the former situation by examining the
      effect of incident radiation that is linearly or circularly polarized and
      traveling in a direction that is parallel or perpendicular to the intermolecular
      distance vector. After tumble averaging, all polarization dependence of the
      energy shift vanishes. In both cases the interaction energy is directly
      proportional to the irradiance of the applied field, and is discriminatory,
      changing sign when one optically active species is replaced by its enantiomer.
      The asymptotic behavior of the energy shift at the limits of large and small
      separations is also studied.

PMID- 16409034
TI  - Beyond the resonant dipole interaction model: resolution of a discrepancy between
      experimental and calculated structures of the carbon dioxide cyclic planar
      trimer.
AB  - A dimer and two trimers of carbon dioxide are known experimentally and have also
      been studied computationally. Whereas the calculated and experimental structures
      are in excellent agreement for the dimer and in fair agreement for the nonplanar
      trimer of C2 symmetry, the cyclic planar trimer shows a significant discrepancy
      in the angle beta which measures the deviation from D(3h) symmetry. All
      calculations yield for this angle values around 40 degrees in contrast to the
      experimental angle of (33.8+/-0.5) degrees . The latter was obtained from the
      experimental shift of the asymmetric vibrational stretch line of the trimer
      relative to the monomer using the resonant dipole-dipole interaction model. This
      model corresponds to the leading term in the molecular transition multipole
      expansion (TMPE) of the electrostatic coupling contribution to vibrational
      shifts. In this paper we go beyond the resonant dipole-dipole interaction model
      and include higher-order moments. To this end we use the first-order perturbation
      approach in combination with the (CO2)2 ab initio symmetry-adapted perturbation
      theory (SAPT)-s potential to calculate the vibrational shifts and scale the CO2
      SAPT-s point charges to reproduce the experimental transition dipole moment of
      the gas-phase CO2 asymmetric stretch. The transition dipole-dipole term in the
      TMPE of the electrostatic coupling plays a predominant role in the vibrational
      shifts of the CO2 dimer and nonplanar trimer, however, to explain the vibrational
      shifts of the cyclic planar trimer the inclusion of the higher-order
      vibrationally induced moments is needed. As the angle beta in this trimer
      approaches the value of 40 degrees the dipole-dipole term in the electrostatic
      coupling disappears and the sum of the higher-order terms becomes important for
      the correct description of the vibrational shifts. Hence applying the resonant
      dipole-dipole interaction model to the experimentally observed vibrational shift
      for the cyclic planar trimer gives the wrong angle beta for this trimer. The
      higher-order terms in the TMPE of the electrostatic coupling which are not
      negligible for the vibrational shifts of the cyclic planar trimer include
      vibrationally induced dipole-octupole and quadrupole-quadrupole interactions.

PMID- 16409035
TI  - Pulse shaping effect on two-photon excitation efficiency of alpha-perylene
      crystals and perylene in chloroform solution.
AB  - We demonstrated that the two-photon excitation efficiency of perylene in
      chloroform solution as well as that of crystalline perylene was dramatically
      increased by optimizing the shape of intense femtosecond laser pulses of a
      regenerative amplifier output. The efficiency was three times higher than for an
      unshaped single femtosecond pulse with the pulse width of shorter than 50 fs. The
      pulse shape optimized for the solution sample was a pulse train with a repetition
      frequency of about 340 cm(-1), and the pulse shape optimized for crystalline
      perylene was very similar. These results supported our previous findings on alpha
      perylene crystals using weak femtosecond pulses from a mode-locked laser
      oscillator [T. Okada et al. J. Chem. Phys. 121, 6385 (2004)]. Furthermore, it was
      confirmed that the shaped pulse optimized for the liquid sample could also
      increase the two-photon excitation efficiency of alpha-perylene crystals and vice
      versa. We concluded that the mechanism for the increase in excitation efficiency
      of perylene in chloroform was almost the same as that for alpha-perylene crystal,
      and that the efficiency increased mainly through intramolecular dynamical
      processes. Processes involving intermolecular interactions and/or energy states
      delocalized over the crystal cannot play the major role.

PMID- 16409036
TI  - High-pressure Brillouin scattering of amorphous BeH2.
AB  - High-pressure micro-Brillouin scattering is employed to investigate the pressure
      dependence of the sound velocity, refractive index, equation of state, and
      mechanical properties of amorphous BeH2. The refractive index n has been
      determined by using two scattering geometries (70 degrees and 180 degrees). The
      equation of state is deduced from the pressure dependences of the sound velocity.
      The bulk modulus is 14.2 (+/-3.0) GPa and its pressure derivative is 5.3 (+/
      0.5). The polarizability is calculated from the refractive index and the density
      of the material. It increases with pressure while Poisson's ratio decreases with
      pressure.

PMID- 16409038
TI  - Temperature-induced structural changes in glassy, supercooled, and molten silica
      from 77 to 2150 K.
AB  - In situ polarized and depolarized Raman spectra of glassy, supercooled, and
      molten SiO2 have been measured over the broad temperature range 77-2150 K in an
      effort to examine possible structural changes caused by temperature variation. A
      new experimental setup using a CO2 laser for heating the sample has been designed
      allowing measurement with controllable blackbody radiation background at
      temperatures up to 2200 K. Careful and systematic relative intensity measurements
      and the use of the isotropic and anisotropic Raman representation of the spectra
      revealed hidden bands in the bending mode region and resolved bands in the
      stretching region of the spectra. Overall the spectra behavior shows similarities
      with the spectra of the recently studied tetrahedral glasses/melts of ZnCl2 and
      ZnBr2. Increasing temperature causes subtle changes of the relative intensities
      within the silicon-oxygen stretching region at approximately 750-850 cm(-1) and
      gives rise to a new band at approximately 930 cm(-1). The spectral behavior is
      interpreted to indicate that the "SiO42" tetrahedra are bound to each other to
      form the network by apex-bridging and partly by edge-bridging oxygens. The
      network structure of the glass/melt is formed by mixing a variety of tetrahedra
      participating in "open" (cristobalitelike), "cluster" (supertetrahedra), and
      "chain" edge-bridged substructures bound to each other by bridging oxygens. A
      weak in intensity but strongly polarized composite band is resolved at
      approximately 1400 cm(-1) and is assigned to Si[Double Bond]O terminal bond
      frequency. Temperature rise increases the concentration of the terminal bonds by
      breaking up the network. These structural changes are reminiscent of the
      polyamorphic transformations occurring in silica as has recently been predicted
      by computer simulations. At low frequencies the Raman spectra reveal the presence
      of the Boson peak at approximately 60 cm(-1) which is well resolved even above
      melting temperature up to 2150 K.

PMID- 16409037
TI  - Light-scattering study of vibrational relaxation in liquid xylenes.
AB  - Brillouin spectra obtained in dynamic light-scattering experiments are reported
      for the three isomeric xylenes (ortho-, meta-, and paradimethylbenzenes) between
      288 and 363 K. Limiting sound velocities and relaxation times, as obtained from
      the polarized spectra using the theory developed by Mountain [J. Res. Natl. Bur.
      Stand. 70A, 207 (1966)], reveal the existence of a relaxation process. Our
      results suggest that the relaxation process in liquid xylenes has a purely
      vibrational nature. Vibrational-translational energy exchanges in xylenes are
      analyzed in terms of available molecular models and compared to those previously
      obtained for toluene and benzene. The results presented here confirm the
      important role played by the molecular geometry in the vibrational relaxation
      process, as the relative arrangement of the methyl groups has significant effect
      in determining the relaxing vibrational modes.

PMID- 16409039
TI  - Drift of spiral waves controlled by a polarized electric field.
AB  - The drift behavior of spiral waves under the influence of a polarized electric
      field is investigated in the light that both the polarized electric field and the
      spiral waves possess rotation symmetry. Numerical simulations of a reaction
      diffusion model show that the drift velocity of the spiral tip can be controlled
      by changing the polarization mode of the polarized electric field and some
      interesting drift phenomena are observed. When the electric field is circularly
      polarized and its rotation follows that of the spiral, the drift speed of the
      spiral tip reaches its maximal value. On the contrary, opposite rotation between
      the spiral and electric field locks the drift of the spiral tip. Analytical
      results based on the weak deformation approximation are consistent with the
      numerical results. We hope that our theoretical results will be observed in
      experiments, such as the Belousov-Zhabotinsky reaction.

PMID- 16409040
TI  - Evaluation of surface tension and Tolman length as a function of droplet radius
      from experimental nucleation rate and supersaturation ratio: metal vapor
      homogeneous nucleation.
AB  - Zinc and silver vapor homogeneous nucleations are studied experimentally at the
      temperature from 600 to 725 and 870 K, respectively, in a laminar flow diffusion
      chamber with Ar as a carrier gas at atmospheric pressure. The size, shape, and
      concentration of aerosol particles outcoming the diffusion chamber are analyzed
      by a transmission electron microscope and an automatic diffusion battery. The
      wall deposit is studied by a scanning electron microscope (SEM). Using SEM data
      the nucleation rate for both Zn and Ag is estimated as 10(10) cm(-3) s(-1). The
      dependence of critical supersaturation on temperature for Zn and Ag measured in
      this paper as well as Li, Na, Cs, Ag, Mg, and Hg measured elsewhere is analyzed.
      To this aim the classical nucleation theory is extended by the dependence of
      surface tension on the nucleus radius. The preexponent in the formula for the
      vapor nucleation rate is derived using the formula for the work of formation of
      noncritical embryo [obtained by Nishioka and Kusaka [J. Chem. Phys. 96, 5370
      (1992)] and later by Debenedetti and Reiss [J. Chem. Phys. 108, 5498 (1998)]] and
      Reiss replacement factor. Using this preexponent and the Gibbs formula for the
      work of formation of critical nucleus the dependence of surface tension on the
      radius R(S) of the surface of tension is evaluated from the nucleation data for
      above-mentioned metals. For the alkali metals and Ag the surface tension was
      determined to be a strong function of R(S). For the bivalent metals (Zn, Hg, and
      Mg) the surface tension was independent of radius in the experimental range. A
      new formula for the Tolman length delta as a function of surface tension and
      radius R(S) is derived by integration of Gibbs-Tolman-Koenig equation assuming
      that delta is a monotonic function of radius. The formula derived is more correct
      than the Tolman formula and convenient for the elaboration of experimental data.
      Using this formula the values of delta are determined as a function of R(S) from
      the experimental nucleation data. It is determined that all the metals considered
      are characterized by strong dependence of delta on radius; for the bivalent
      metals delta changes sign.

PMID- 16409041
TI  - Diffusivity, excess entropy, and the potential-energy landscape of monatomic
      liquids.
AB  - The connection between thermodynamic, transport, and potential-energy landscape
      features is studied for liquids with Lennard-Jones-type pair interactions using
      both microcanonical molecular-dynamics and isothermal-isobaric ensemble Monte
      Carlo simulations. Instantaneous normal-mode and saddle-point analyses of two
      variants of the monatomic Lennard-Jones liquid have been performed. The
      diffusivity is shown to depend linearly on several key properties of
      instantaneous and saddle configurations-the energy, the fraction of negative
      curvature directions, and the mean, maximum, and minimum eigenvalues of the
      Hessian. Since the Dzugutov scaling relationship also holds for such systems
      [Nature (London) 381, 137 (1996)], the exponential of the excess entropy, within
      the two-particle approximation, displays the same linear dependence on energy
      landscape properties as the diffusivity.

PMID- 16409042
TI  - Electron spin relaxation of N@C60 in CS2 in CS2.
AB  - We examine the temperature dependence of the electron spin relaxation times of
      the molecules N@C60 and N@C70 (which comprise atomic nitrogen trapped within a
      carbon cage) in liquid CS2 solution. The results are inconsistent with the
      fluctuating zero-field splitting (ZFS) mechanism, which is commonly invoked to
      explain electron spin relaxation for S> or =1 spins in liquid solution, and is
      the mechanism postulated in the literature for these systems. Instead, we find an
      Arrhenius temperature dependence for N@C60 , indicating the spin relaxation is
      driven primarily by an Orbach process. For the asymmetric N@C70 molecule, which
      has a permanent ZFS, we resolve an additional relaxation mechanism caused by the
      rapid reorientation of its ZFS. We also report the longest coherence time (T2)
      ever observed for a molecular electron spin, being 0.25 ms at 170 K.

PMID- 16409043
TI  - Nonlinear fingering dynamics of reaction-diffusion acidity fronts: self-similar
      scaling and influence of differential diffusion.
AB  - Nonlinear interactions between chemical reactions and buoyancy-driven Rayleigh
      Taylor instability of reaction-diffusion acidity fronts of the chlorite
      tetrathionate (CT) reaction are studied theoretically in a vertical Hele-Shaw
      cell or a porous medium. To do so, we perform a numerical integration of a two
      variable reaction-diffusion model of the CT system coupled through an advection
      term to Darcy's law ruling the evolution of the velocity field of the fluid. The
      fingering dynamics of these chemical fronts is characterized by the appearance of
      several fingers at onset. These fingers then undergo coarsening and eventually
      merge to form one single symmetric finger. We study this asymptotic dynamics as a
      function of the three dimensionless parameters of the problem, i.e., the
      Damkohler number Da, the diffusivity ratio delta of the two chemical species, and
      the Rayleigh number Ra constructed here on the basis of the width L(y) of the
      system. For moderate values of Ra, the asymptotic single finger is shown to have
      self-similar scaling properties while above a given value of Ra, which depends on
      the other values of the parameters, tip splitting comes into play. Increasing the
      difference of diffusivities of the two chemical species (i.e., increasing delta)
      leads to more efficient coarsening and smaller asymptotic fingers. Experimental
      procedures to verify our predictions are proposed.

PMID- 16409044
TI  - Enhanced translational diffusion of rubrene in sucrose benzoate.
AB  - The translational diffusion of rubrene in the fragile molecular glass former,
      sucrose benzoate (SB) (fragility index m approximately 94), has been studied from
      T(g)+6 K to T(g)+71 K(T(g)=337 K) by using the technique of holographic
      fluorescence recovery after photobleaching. In the temperature range of the
      measurements, the translational relaxation functions were observed to decay
      exponentially, indicating that Fick's law of diffusion governs the translational
      motion of rubrene in sucrose benzoate. The value of the translational diffusion
      coefficient D(T) obtained from the 1e time of the translational relaxation
      function varied from 5.3 x 10(-15) cm2 s(-1) at 343 K to 5.0x10(-9) cm2 s(-1) at
      408 K. The temperature dependence of D(T) for diffusion of rubrene in SB is
      compared with that of the viscosity and the dielectric relaxation time tau(D) of
      SB. The temperature dependence of D(T) is weaker than that of Teta for T<1.2T(g)
      but tracks the reciprocal of the dielectric relaxation time 1tau(D) for
      1.05T(g)<T<1.21T(g). The translational diffusion coefficient at T(g) is enhanced
      by a factor of approximately 2.5x10(2) over the value predicted by the Stokes
      Einstein equation. The decoupling of probe diffusion from the viscosity is
      characterized by a scaling law, D(T) approximately eta(-xi), with xi=0.729.

PMID- 16409045
TI  - Electronic structures of size-selected single-layered platinum clusters on
      silicon(111)-7x7 surface at a single cluster level by tunneling spectroscopy.
AB  - Tunneling spectra of size-selected single-layered platinum clusters (size range
      of 5-40) deposited on a silicon(111)-7x7 surface were measured individually at a
      temperature of 77 K by means of a scanning tunneling microscope (STM), and the
      local electronic densities of states of individual clusters were derived from
      their tunneling spectra measured by placing an STM tip on the clusters. In a bias
      voltage (V(s)) range from -3 to 3 V, each tunneling spectrum exhibits several
      peaks assignable to electronic states associated with 5d states of a constituent
      platinum atom and an energy gap of 0.1-0.6 eV in the vicinity of V(s)=0. Even
      when platinum cluster ions having the same size were deposited on the
      silicon(111)-7x7 surface, the tunneling spectra and the energy gaps of the
      deposited clusters are not all the same but can be classified in shape into
      several different groups; this finding is consistent with the observation of the
      geometrical structures of platinum clusters on the silicon(111)-7x7 surface. The
      mean energy gap of approximately 0.4 eV drops to approximately 0.25 eV at the
      size of 20 and then decreases gradually as the size increases, consistent with
      our previous finding that the cluster diameter remains unchanged, but the number
      density of Pt atoms increases below the size of 20 while the diameter increases,
      but the density does not change above it. It is concluded that the mean energy
      gap tends to decrease gradually with the mean cluster diameter. The dependence of
      the mean energy gap on the mean Pt-Pt distance shows that the mean energy gap
      decreases sharply when the mean Pt-Pt distance exceeds that of a platinum metal
      (0.28 nm).

PMID- 16409046
TI  - Thermal relaxation mechanism and role of chemical functionalization in fullerene
      solutions.
AB  - Using molecular-dynamics simulations we investigate thermal relaxation of C60 and
      C84 molecules suspended in octane liquid. Pristine fullerenes exhibit relatively
      slow relaxation due to weak thermal coupling with the liquid. A comparison of the
      interfacial transport characteristics obtained from relaxation simulations with
      those obtained from equilibrium simulations and fluctuation-dissipation theorem
      analysis demonstrates that the relaxation process involves two main steps: (i)
      energy flow from high- to low-frequency modes within the fullerene, and (ii)
      energy flow from low-frequency fullerene modes to the liquid. Functionalization
      of fullerenes with alkene chains leads to significant reduction of the thermal
      relaxation time. The relaxation time of functionalized fullerenes becomes
      independent from the functionalizing chain length beyond approximately 10 carbon
      segments; this can be understood in terms of thermal conductivity along the chain
      and heat transfer between the chain and the solvent.

PMID- 16409047
TI  - Evidence of a two-stage thermal denaturation process in lysozyme: a Raman
      scattering and differential scanning calorimetry investigation.
AB  - Raman spectroscopy (in the low-frequency range and the amide I band region) and
      modulated differential scanning calorimetry investigations have been used to
      analyze temperature-induced structural changes in lysozyme dissolved in 1H2O and
      2H2O in the thermal denaturation process. Low-frequency Raman data reveal a
      change in tertiary structure without concomitant unfolding of the secondary
      structure. Calorimetric data show that this structural change is responsible for
      the configurational entropy change associated with the strong-to-fragile liquid
      transition and correspond to about 1/3 of the native-denaturated transition
      enthalpy. This is the first stage of the thermal denaturation which is a
      precursor of the secondary structure change and is determined to be strongly
      dependent on the stability of the hydrogen-bond network in water. Low-frequency
      Raman spectroscopy provides information on the flexibility of the tertiary
      structure (in the native state and the transient folding state) in relation to
      the fragility of the mixture. The unfolding of the secondary structure appears as
      a consequence of the change in the tertiary structure and independent of the
      solvent. Protein conformational stability is directly dependent on the stability
      of the native tertiary structure. The structural transformation of tertiary
      structure can be detected through the enhanced 1H/2H exchange inhibited in native
      proteins. Taking into account similar features reported in the literature
      observed for different proteins it can be considered that the two-stage
      transformation observed in lysozyme dissolved in water is a general mechanism for
      the thermal denaturation of proteins.

PMID- 16409048
TI  - Molecular-dynamics simulations of binary structure II hydrogen and
      tetrahydrofurane clathrates.
AB  - The binary structure II hydrogen and tetrahydrofurane (THF) clathrates are
      studied with molecular-dynamics simulations. Simulations are done at pressures of
      120 and 1.013 bars for temperatures ranging from 100 to 273 K. For the small
      cages of the structure II unit cell, H2 guest molecule occupancies of 0, 16
      (single occupancy), and 32 (double occupancy) are considered. THF occupancies of
      0-8 in the large cages are studied. For cases in which THF does not occupy all
      large cages in a unit cell, the remaining large cages can be occupied with sets
      of four H2 guest molecules. The unit-cell volumes and configurational energies
      are compared in the different occupancy cases. Increasing the small cage
      occupancy leads to an increase in the unit-cell volume and thermal-expansion
      coefficient. Among simulations with the same small cage occupancy, those with the
      large cages containing 4H2 guests have the largest volumes. The THF guest
      molecules have a stabilizing effect on the clathrate and the configurational
      energy of the unit cell decreases linearly as the THF content increases. For
      binary THF + H2 clathrates, the substitution of the THF molecules in the large
      cages with sets of 4H2 molecules increases the configurational energy. For the
      binary clathrates, various combinations of THF and H2 occupancies have similar
      configurational energies.

PMID- 16409049
TI  - Behavior of rodlike polyelectrolytes near an oppositely charged surface.
AB  - The behavior of highly charged short rodlike polyelectrolytes near oppositely
      charged planar surfaces is investigated by means of Monte Carlo simulations. A
      detailed microstructural study, including monomer and fluid charge distributions
      and chain orientation, is provided. The influence of chain length, substrate's
      surface-charge density, and image forces is considered. Due to the lower chain
      entropy (compared to flexible chains), our simulation data show that rodlike
      polyelectrolytes can, in general, better adsorb than flexible ones do.
      Nonetheless, at low substrate-dielectric constant, it is found that repulsive
      image forces tend to significantly reduce this discrepancy.

PMID- 16409050
TI  - K and mixed K+O adlayers on Rh(110).
AB  - The evolution of the structure of the adlayers and the substrate during
      adsorption of K and coadsorption of K and O on Rh(110) is studied by scanning
      tunneling microscopy and low-energy electron diffraction. The K adsorption at
      temperature above 450 K leads to consecutive (1x4), (1x3), and (1x2) missing-row
      reconstructions for coverage up to 0.12 ML, which revert back to (1x3) and (1x4)
      with increasing coverage up to 0.21 ML. The coadsorption of different oxygen
      amount at T>450 K and eventually following reduction-reoxidation cycles led to a
      wealth of coadsorbate structures, all involving substrate missing-row-type
      reconstructions, some including segmentation of Rh rows along the [110]
      direction. The presence of K stabilizes the (1x2) missing-row reconstruction,
      which facilitates the formation of a great variety of very open (10x2)-type
      reconstructions at high oxygen coverage, not observed in the single adsorbate
      systems.

PMID- 16409051
TI  - Periodical forcing for the control of chaos in a chemical reaction.
AB  - Control of the chaotic behavior of a chemical system can be achieved perturbing
      periodically some control parameters of the system. This procedure based on
      external forcing, which is based on the phenomenon of resonance, can change a
      chaotic behavior into a periodical one by means of the application of a
      sinusoidal perturbation. In this paper, the influence of a periodical modulation
      added to the parameter controlling the oxygen adsorption rate in a cellular
      automaton (CA) model studying CO oxidation is analyzed. This CA model considers
      the oxidation reaction of CO on a catalytic surface, taking into account the
      catalyst temperature variation in order to analyze the reaction time oscillatory
      behavior. Simulations of the CA model exhibit chaotic and quasiperiodical
      behaviors, and it can be shown that the periodical forcing strategy can suppress
      the chaotic dynamics by means of the stabilization of periodical solutions.

PMID- 16409052
TI  - Molecular-dynamics simulation of a ceramide bilayer.
AB  - Ceramide is the simplest lipid in the biologically important class of
      glycosphingolipids. Ceramide is an important signaling molecule and a major
      component of the strateum corneum layer in the skin. In order to begin to
      understand the biophysical properties of ceramide, we have carried out a
      molecular-dynamics simulation of a hydrated 16:0 ceramide lipid bilayer at 368 K
      (5 degrees above the main phase transition). In this paper we describe the
      simulation and present the resulting properties of the bilayer. We compare the
      properties of the simulated ceramide bilayer to an earlier simulation of 18:0
      sphingomyelin, and we discuss the results as they relate to experimental data for
      ceramide and other sphingolipids. The most significant differences arise at the
      lipid/water interface, where the lack of a large ceramide polar group leads to a
      different electron density and a different electrostatic potential but,
      surprisingly, not a different overall "dipole potential," when ceramide is
      compared to sphingomyelin.

PMID- 16409053
TI  - Calculation of the surface tension of oxygen using molecular-dynamics
      simulations.
AB  - The surface tension of oxygen at the liquid-vapor interface is calculated for the
      temperature range of 60-90 K using molecular-dynamics simulations and is shown to
      be within 1.0% error of experimental values for most of the temperatures studied.
      The potential used here is the same as in our previous study on liquid oxygen
      alone [S. D. Bembenek and B. M. Rice, J. Chem. Phys. 113, 2354 (2000)] and was
      optimized with an innovative statistical-mechanical method. The potential does
      not use a long-range cutoff nor a tail correction, which are usually considered
      necessary to obtain accurate values for the surface tension. We reason that the
      accuracy in surface tension is directly related to our parametrization method for
      the potential.

PMID- 16409054
TI  - A comparative study of the polyaniline thin films produced by the cluster beam
      deposition and laser ablation methods.
AB  - Polyaniline (PANI) thin films have been prepared by applying the novel neutral
      and ionized cluster beam deposition (NCBD and ICBD) methods and the pulsed laser
      deposition (PLD) technique to the PANI samples of half-oxidized emeraldine base
      (EB-PANI) and protoemeraldine base forms in a high-vacuum condition.
      Characterization of the oxidation states and structural changes of pristine and
      doped thin films has been performed by Fourier transform infrared spectroscopy,
      ultraviolet-visible spectroscopy, and x-ray photoelectron spectroscopy.
      Spectroscopic measurements demonstrate that the dominant structure of NCBD and
      ICBD thin films corresponds to the reduced leucoemeraldine base state, whereas
      the chemical composition of PLD thin films depends critically on the laser
      fluence and the molecular weight of PANI target. The congruent deposition is only
      obtained for the PLD films deposited by the laser-induced decomposition of the
      low-molecular-weight targets in the low to intermediate fluence regime (below 100
      mJ/cm2 with a pulse duration of 7 ns). The surface morphology examined by atomic
      force microscopy measurements shows that the cluster and laser beams are
      effective in producing smooth, uniform polymeric thin films. After I2 and HCl
      doping, the electrical conductivities of the NCBD, ICBD, and particularly PLD
      thin films are increased significantly. The higher conductivity of PLD films is
      ascribed to higher amounts of quinoid di-imine doping sites in the EB-PANI state,
      and the overall structure-conductivity characteristics are consistent with the
      spectroscopic observations.

PMID- 16409055
TI  - Energetics of formation of TiGa3As4 and TiGa3P4 intermediate band materials.
AB  - Using density functional theory quantum methods, total energy values and
      vibrational properties have been computed, and thermodynamic properties
      evaluated, for Ti-substituted GaAs and GaP, proposed as candidates for
      intermediate band photovoltaic cells. The calculations predict that the formation
      of these materials from the binary compounds implies an increase in total energy
      (that is ascribed largely to the change in coordination undergone by Ti, from six
      fold to four-fold), and thus phase separation rather than mixed compound
      formation would be favored. However, the mentioned increase is not larger (for
      the arsenide case it is actually smaller) than that predicted for Mn-substituted
      GaAs, a material which has been experimentally made, and therefore the obtention
      of these Ti-substituted materials is expected to be feasible as well. Vibrational
      and disorder entropy contributions to the formation free energy of the ternary
      compounds have been also computed; they compensate partially for the total energy
      increase, and indicate that the thermodynamic feasibility of the materials
      synthesis improves for low Ti concentrations and high temperature conditions.

PMID- 16409057
TI  - Transport in polymer-gel composites: response to a bulk concentration gradient.
AB  - This paper examines the response of electrolyte-saturated polymer gels, embedded
      with charged spherical inclusions, to a weak gradient of electrolyte
      concentration. An electrokinetic model was presented in an earlier publication,
      and the response of homogeneous composites to a weak electric field was
      calculated. In this work, the influence of the inclusions on bulk ion fluxes and
      the strength of an electric field (or membrane diffusion potential) induced by
      the bulk electrolyte concentration gradient are computed. Effective ion diffusion
      coefficients are significantly altered by the inclusions, so-depending on the
      inclusion surface charge or zeta potential-asymmetric electrolytes can behave as
      symmetrical electrolytes and vice versa. The theory also quantifies the strength
      of flow driven by concentration-gradient-induced perturbations to the equilibrium
      diffuse double layers. Similarly to diffusiophoresis, the flow may be either up
      or down the applied concentration gradient.

PMID- 16409056
TI  - Ultrafast heterogeneous electron transfer reactions: comparative theoretical
      studies on time- and frequency-domain data.
AB  - Recent theoretical studies on linear absorption spectra of dye-semiconductor
      systems [perylene attached to nanostructured TiO2, L. Wang et al., J. Phys. Chem.
      B 109, 9589 (2005)] are extended here in different respects. Since the systems
      show ultrafast photoinduced heterogeneous electron transfer the time-dependent
      formulation used to compute the absorbance is also applied to calculate the
      temporal evolution of the sub-100 fs charge injection dynamics after a 10 fs
      laser-pulse excitation. These studies complement our recent absorption spectra
      fit for two perylene bridge-anchor group TiO2 systems. Moreover, the time
      dependent formulation of the absorbance is confronted with a frequency-domain
      description. The latter underlines the central importance of the self-energy
      caused by the coupling of the dye levels to the semiconductor band continuum. The
      used model is further applied to study the effect of different parameters such as
      (1) the dependence on the reorganization energies of the involved intramolecular
      transitions, (2) the effect of changing the transfer integral which couples the
      excited dye state with the band continuum, and (3) the effect of the concrete
      form of the semiconductor band density of states. Emphasis is also put on the
      case where the charge injection level of the dye is near or somewhat below the
      band edge. This nicely demonstrates the change from a structureless absorption to
      a well-resolved vibrational progression including characteristic shifts of the
      absorption lines which are a direct measure for the dye-semiconductor coupling.

PMID- 16409058
TI  - A mode coupling theory description of the short- and long-time dynamics of
      nematogens in the isotropic phase.
AB  - Optical heterodyne-detected optical Kerr effect (OHD-OKE) experimental data are
      pre-sented on nematogens 4-(trans-4-n-octylcyclohexyl)isothiocyanatobenzene (8
      CHBT), and 4-(4-pentyl-cyclohexyl)-benzonitrile (5-PCH) in the isotropic phase.
      The 8-CHBT and 5-PCH data and previously published data on 4-pentyl-4
      biphenylcarbonitrile (5-CB) are analyzed using a modification of a schematic mode
      coupling theory (MCT) that has been successful in describing the dynamics of
      supercooled liquids. At long time, the OHD-OKE data (orientational relaxation)
      are well described with the standard Landau-de Gennes (LdG) theory. The data
      decay as a single exponential. The decay time diverges as the isotropic to
      nematic phase transition is approached from above. Previously there has been no
      theory that can describe the complex dynamics that occur at times short compared
      to the LdG exponential decay. Earlier, it has been noted that the short-time
      nematogen dynamics, which consist of several power laws, have a functional form
      identical to that observed for the short time behavior of the orientational
      relaxation of supercooled liquids. The temperature-dependent orientational
      dynamics of supercooled liquids have recently been successfully described using a
      schematic mode coupling theory. The schematic MCT theory that fits the
      supercooled liquid data does not reproduce the nematogen data within experimental
      error. The similarities of the nematogen data to the supercooled liquid data are
      the motivation for applying a modification of the successful MCT theory to
      nematogen dynamics in the isotropic phase. The results presented below show that
      the new schematic MCT theory does an excellent job of reproducing the nematogen
      isotropic phase OHD-OKE data on all time scales and at all temperatures.

PMID- 16409059
TI  - The dependence of nanostructures on the molecule rigidity of A2(B4)2-type
      miktoarm block copolymer.
AB  - Using the dissipative particle dynamics simulation technique, we have studied the
      influence of the molecule rigidity on the nanostructures of the A2(B4)2-type
      miktoarm block copolymers. A typical spherical micellar ordered structure is
      obtained for a coil-coil miktoarm block copolymer in melt. By introducing a bond
      angle potential in our model to enhance the molecule rigidity systematically, we
      find, respectively, a hexagonal cylindrical structure and a parallel ellipsoid in
      lamellae structure which is discovered for the first time.

PMID- 16409060
TI  - Characterization of tunneling systems in molecular versus polymer glasses by high
      pressure photon echo spectroscopy.
AB  - Intrinsic differences between tunneling two-level systems (TLSs) in molecular
      versus polymeric glasses are revealed by studying the effect of compression on
      TLS dynamics. Photon echo studies under variable low-temperature (1.1-2.3 K) and
      high-pressure (0-30 kbar) conditions have been performed to contrast the effect
      of compression on molecular [2-methyl-tetrahydrofuran (2MTHF)] versus polymer
      [Polymethylmethacrylate (PMMA)] glasses. The pressure-induced reduction in the
      magnitude of the optical dephasing rate of rhodamine 640 in a molecular glass
      (2MTHF) is found to be comparable to the volume decrease of the glass (e.g.,
      approximately 20% at 30 kbar), indicating that TLSs in 2MTHF are associated with
      void space or low-density regions of the glass. In contrast, the relative
      pressure insensitivity observed for organic polymer glasses (PMMA) supports the
      idea that these TLSs are associated with side chain defects. The power-law
      exponent for the temperature-dependent dephasing in 2MTHF also decreased
      significantly at high pressure, suggesting a change in the form of the TLS
      density of states upon compression of the molecular glass.

PMID- 16409061
TI  - A self-consistent density-functional approach to the structure of nonuniform
      binary hard-core Yukawa mixtures.

PMID- 16409062
TI  - Solubility of simple, nonpolar compounds in TIP4P-Ew.

PMID- 16409064
TI  - Targeted DNA transfection into the mouse central nervous system using laser
      induced stress waves.
AB  - We investigated the feasibility of gene transfer into the mouse central nervous
      system (CNS) by applying nanosecond pulsed laser-induced stress waves (LISWs).
      Intraventricular or hippocampal injection of a reporter gene [enhanced green
      fluorescent protein (EGFP)] followed by application of LISWs showed this method
      to be efficient in the CNS of newborn and adult mice. Cells expressing EGFP
      reside at least 3.5 mm from the surface of the tissue, while no apparent damage
      was detected. Additionally, expression of EGFP was limited to the area that was
      exposed to LISWs. Using this method, the formulation of plasmid DNA by cationic
      transfer reagent polyethylenimine proved to be effective for improving transfer
      efficiency into the CNS.

PMID- 16409065
TI  - Complex degree of mutual polarization of biological tissue coherent images for
      the diagnostics of their physiological state.
AB  - This is the first attempt devoted to the 1st-4th order statistic analysis of the
      complex degree of mutual polarization of biological tissues coherent images. The
      ensemble of diagnostic criteria (skewness and kurtosis of two-dimensional
      distributions of complex degree of mutual polarization) of pathological changes
      of muscular and connective (skin derma) tissues is defined.

PMID- 16409066
TI  - Erythrocyte structure and dynamics quantified by Hilbert phase microscopy.
AB  - We present a new quantitative method for investigating red blood cell morphology
      and dynamics. The instrument integrates quantitative phase microscopy with an
      inverted microscope, which makes it particularly suitable for the noninvasive
      assessment of live erythrocytes. In particular, we demonstrate the ability of
      this approach to quantify noninvasively cell volume and dynamic morphology. The
      subnanometer path-length sensitivity at the millisecond time scales is
      exemplified by measuring the hemoglobin flow out of the cell during hemolysis.

PMID- 16409067
TI  - Effect of errors in baseline optical properties on accuracy of transabdominal
      near-infrared spectroscopy in fetal sheep brain during hypoxic stress.
AB  - A continuous-wave (cw) near-infrared spectroscopy (NIRS) instrument has been
      developed to noninvasively quantify fetal cerebral blood oxygen saturation
      (StO2). A linear Green's function formulism was used to analytically solve the
      photon diffusion equation and extract the time-varying fetal tissue oxy- and
      deoxy-hemoglobin concentrations from the NIR measurements. Here we explored the
      accuracy with which this instrument can be expected to perform over a range of
      fetal hypoxic states. We investigated the dependence of this accuracy on the
      accuracy of the reference optical properties chosen based on the literature. The
      fetal oxygenation of a pregnant ewe model was altered via maternal aortic
      occlusion. The NIR cw instrument was placed on the maternal abdomen directly
      above the fetal head, continuously acquiring diffuse optical measurements. Blood
      was sampled periodically from the fetus to obtain fetal arterial saturation
      (SaO2) measurements from blood gas analysis. The NIR StO2 values were compared
      with the fetal SaO2 measurements. Variations in the NIR results due to
      uncertainty in the reference optical properties were relatively small within the
      fetal SaO2 range of 30 to 80%. Under hypoxic conditions, however, the variability
      of the NIR StO2 calculations with changes in the assumed reference properties
      became more significant.

PMID- 16409068
TI  - Polarized laser Doppler perfusion imaging--reduction of movement-induced
      artifacts.
AB  - Laser Doppler perfusion imaging (LDPI) enables superficial tissue perfusion
      assessment, but is sensitive to tissue motion not related to blood cells. The aim
      was to investigate if a polarization technique could reduce movement-induced
      artifacts. A linearly polarized laser and a cross-polarized filter, placed in
      front of the detectors, were used to block specular reflection. Measurements were
      performed with, and without, the polarization filter, at a single site during
      horizontal and vertical movement of skin tissue (index finger, twelve subjects, n
      = 112) and of a flow model (n = 432), with varying surface structures.
      Measurements were repeated during different flow conditions and at increased skin
      specular reflection. Statistical analysis was performed using ANOVA models. The
      perfusion signal was lower (p < 0.001, skin and p < 0.05, flow model) using the
      polarization filter, due to movement artifact reduction. No significant influence
      from surface structure was found when using the polarization filter. Movement
      artifacts were lower (p < 0.05) in the vertical movement direction, however,
      depending on flow conditions for skin measurements. Increased skin specular
      reflection gave rise to large movement artifacts without the polarization filter.
      In conclusion, the polarized LDPI technique reduces movement artifacts and is
      particularly appropriate when assessing, e.g., ulcers and burns, where specular
      reflection is high.

PMID- 16409069
TI  - Application of infrared light for in vivo neural stimulation.
AB  - A novel method for damage-free, artifact-free stimulation of neural tissue using
      pulsed, low-energy infrared laser light is presented. Optical stimulation elicits
      compound nerve and muscle potentials similar to responses obtained with
      conventional electrical neural stimulation in a rat sciatic nerve model.
      Stimulation and damage thresholds were determined as a function of wavelength
      using a tunable free electron laser source (lambda = 2 to 10 microm) and a solid
      state holmium:YAG laser (lambda = 2.12 microm). Threshold radiant exposure
      required for stimulation varies with wavelength from 0.312 Jcm2 (lambda = 3
      microm) to 1.22 Jcm2 (lambda = 2.1 microm). Histological analysis indicates no
      discernable thermal damage with suprathreshold stimulation. The largest
      damage/stimulation threshold ratios (>6) were at wavelengths corresponding to
      valleys in the IR spectrum of soft tissue absorption (4 and 2.1 microm).
      Furthermore, optical stimulation can be used to generate a spatially selective
      response in small fascicles of the sciatic nerve that has significant advantages
      (e.g., noncontact, spatial resolution, lack of stimulation artifact) over
      conventional electrical methods in diagnostic and therapeutic procedures in
      neuroscience, neurology, and neurosurgery.

PMID- 16409070
TI  - Heterodyne swept-source optical coherence tomography for complete complex
      conjugate ambiguity removal.
AB  - Fourier domain (FD) techniques have increasingly gained attention in optical
      coherence tomography (OCT). This is primarily due to their demonstrated
      sensitivity of two to three orders of magnitude over conventional time-domain
      techniques. FDOCT images are subject to two primary sources of artifacts. First,
      a complex conjugate ambiguity arises because the Fourier transform of the real
      valued spectral interferometric signal is Hermitian symmetric. This ambiguity
      leads to artifactual superposition of reflectors at positive and negative
      pathlength differences between the sample and reference reflectors. Second,
      noninterferometric and sample autocorrelation terms appear at dc, obscuring
      reflectors at zero pathlength difference. We show that heterodyne detection in
      swept-source OCT (SSOCT) enables the resolution of complex conjugate ambiguity
      and the removal of noninterferometric and autocorrelation artifacts. We also show
      that complex conjugate ambiguity resolution via frequency shifting circumvents
      fall-off induced by finite source linewidth in SSOCT when samples are shifted to
      large pathlength differences. We describe an efficient heterodyne SSOCT design
      that enables compensation of power losses from frequency-shifting elements. Last,
      we demonstrate this technique, coupled with wavenumber triggering and electronic
      demodulation, for in vivo imaging of the human anterior eye segment.

PMID- 16409071
TI  - Application of luminescent Eu:Gd2O3 nanoparticles to the visualization of protein
      micropatterns.
AB  - Nanoparticle phosphors made of lanthanide oxides are a promising new class of
      tags in biochemistry because of their large Stokes shift, sharp emission spectra,
      long luminescence lifetime, and good photostability. We demonstrate the
      application of these nanoparticles to the visualization of protein micropatterns.
      Luminescent europium-doped gadolinium oxide (Eu:Gd2O3) nanoparticles are
      synthesized by spray pyrolysis. The size distribution is from 5 to 200 nm. The
      particles are characterized by means of laser-induced fluorescent spectroscopy
      and transmission electron microscopy (TEM). The main emission peak is at 612 nm.
      The nanoparticles are coated with avidin through physical adsorption.
      biotinylated bovine serum albumin (BSA-b) is patterned on a silicon wafer using a
      microcontact printing technique. The wafer is then incubated in a solution of
      avidin-coated nanoparticles. Fluorescent microscopic images reveal that the
      nanoparticles are organized onto designated area, as defined by the microcontact
      printing process. The luminescent nanoparticles do not suffer photobleaching
      during the observation, which demonstrates their suitability as luminescent
      labels for fluorescence microscopy studies. More detailed studies are preformed
      using atomic-force microscopy (AFM) at a single nanoparticle level. The specific
      and the nonspecific binding densities of the particles are qualitatively
      evaluated.

PMID- 16409072
TI  - Planar fluorescence imaging using normalized data.
AB  - Fluorescence imaging of tissues has gained significant attention in recent years
      due to the emergence of appropriate reporter technologies that enable noninvasive
      sensing of molecular function in vivo. Two major approaches have been used so far
      for fluorescence molecular imaging, i.e., epi-illumination (reflectance) imaging
      and fluorescence molecular tomography. Transillumination is an alternative
      approach that has been employed for imaging tissues in the past and could be
      similarly beneficial for fluorescence molecular imaging. We investigate data
      normalization schemes in reflectance and transillumination mode and
      experimentally demonstrate that normalized transillumination offers significant
      advantages over planar reflectance imaging and over nonnormalized methods. Our
      observations, based on phantoms and on postmortem and in vivo mouse measurements
      display image quality improvement, superior depth sensitivity, and improved
      imaging accuracy over the nonnormalized methods examined. Normalized planar
      imaging retains implementation simplicity and could be used to improve on
      standard fluorescence reflectance imaging and as a simplified alternative to the
      more integrated and accurate tomographic methods.

PMID- 16409073
TI  - Extraction of depth-dependent signals from time-resolved reflectance in layered
      turbid media.
AB  - We try a new approach with near-IR time-resolved spectroscopy, to separate
      optical signals originated in the upper layer from those in the lower layer and
      to selectively determine the absorption coefficient (mu(a)) of each layer in a
      two-layered turbid medium. The difference curve in the temporal profiles of light
      attenuation between a target and a reference medium is divided into segments
      along the time axis, and a slope of each segment is calculated to determine the
      depth-dependent mu(a). The depth-dependent mu(a) values are estimated under
      various conditions in which mu(a) and the reduced scattering coefficient (mu(s)')
      of each layer are changed with a Monte Carlo simulation and in phantom
      experiments. Temporal variation of them represents the difference in mu(a)
      between two layers when mu(s)' of a reference is the same as that of the upper
      layer of the target. The discrepancies between calculated mu(a) and the real
      mu(a) depend on the ratio of the real mu(a) of the upper layer to that of the
      lower layer, and our approach enables us to estimate the ratio of mu(a) between
      the two layers. These results suggest the potential that mu(a) of the lower layer
      can be determined by our procedure.

PMID- 16409074
TI  - Spectrally resolved neurophotonics: a case report of hemodynamics and vascular
      components in the mammalian brain.
AB  - We developed a spectral technique that is independent of the light transport
      modality (diffusive or nondiffusive) to separate optical changes in scattering
      and absorption in the cat's brain due to the hemodynamic signal following visual
      stimulation. We observe changes in oxyhemoglobin and deoxyhemoglobin
      concentration signals during visual stimulation reminiscent of the functional
      magnetic resonance imaging (fMRI) blood oxygenation level dependence (BOLD)
      effect. Repeated measurements at different locations show that the observed
      changes are local rather than global. We also determine that there is an apparent
      large decrease in the water concentration and scattering coefficient during
      stimulation. We model the apparent change in water concentration on the
      separation of the optical signal from two tissue compartments. One opaque
      compartment is featureless (black), due to relatively large blood vessels. The
      other compartment is the rest of the tissue. When blood flow increases due to
      stimulation, the opaque compartment increases in volume, resulting in an overall
      decrease of tissue transmission. This increase in baseline absorption changes the
      apparent relative proportion of all tissue components. However, due to
      physiological effects, the deoxyhemoglobin is exchanged with oxyhemoglobin
      resulting in an overall increase in the oxyhemoglobin signal, which is the only
      component that shows an apparent increase during stimulation.

PMID- 16409076
TI  - Measurement of burn depths in rats using multiwavelength photoacoustic depth
      profiling.
AB  - We perform measurement of photoacoustic (PA) signals for burned skin in rats in
      the spectral range of 500 to 650 nm. The wavelength dependence of PA signal
      amplitude shows characteristics similar to those of the absorption spectrum of
      hemoglobin, suggesting that the PA signal originates from blood in the uninjured
      skin tissue under the injured tissue layer. High-contrast signals are obtained in
      the spectral range of 532 to 580 nm. At 550 nm, a PA detector is scanned on the
      wounds and PA tomograms are obtained. The tomograms clearly show the zones of
      stasis, demonstrating that a 2-D PA measurement is useful for burn depth
      assessment.

PMID- 16409075
TI  - Transcranial measurement of diffuse light reflectance from cold-injured brains in
      rats.
AB  - Diagnosis of brain edema is important to manage severe head injuries and
      diseases, but there is no method of noninvasive bedside monitoring of brain
      edema. We speculate that brain edema changes the optical properties of brain
      tissue. To verify this speculation, we perform transcranial measurement of
      diffuse light reflectance from cold-injured brains in rats. To induce edema, a
      liquid nitrogen-cooled copper probe of 3 mm diameter was applied to the right
      parietal bone for 60 s under anesthesia. The rat skull was irradiated with 633-nm
      HeNe laser light and 532-nm Nd:YVO4 laser light, which were used to investigate
      changes in light scattering and blood flow, respectively. Reflectance intensity
      was measured as functions of time and position on the skull. We found that
      reflectance intensities were significantly decreased around the cold injury at
      both 633 and 532 nm, while reflectance was increased in the cold injury at 532
      nm, indicating that cerebral blood volume was decreased in the cold injury. Under
      the condition of decreased cerebral blood volume, the decrease in reflectance
      intensity around the injury suggests that the scattering coefficient of brain
      tissue was reduced due to edema formation in this area.

PMID- 16409077
TI  - Elevation of plasma membrane permeability by laser irradiation of selectively
      bound nanoparticles.
AB  - Irradiation of nanoabsorbers with pico- and nanosecond laser pulses could result
      in thermal effects with a spatial confinement of less than 50 nm. Therefore
      absorbing nanoparticles could be used to create controlled cellular effects. We
      describe a combination of laser irradiation with nanoparticles, which changes the
      plasma membrane permeability. We demonstrate that the system enables molecules to
      penetrate impermeable cell membranes. Laser light at 532 nm is used to irradiate
      conjugates of colloidal gold, which are delivered by antibodies to the plasma
      membrane of the Hodgkin's disease cell line L428 and/or the human large-cell
      anaplastic lymphoma cell line Karpas 299. After irradiation, membrane
      permeability is evaluated by fluorescence microscopy and flow cytometry using
      propidium iodide (PI) and fluorescein isothiocyanate (FITC) dextran. The fraction
      of transiently permeabilized and then resealed cells is affected by the laser
      parameter, the gold concentration, and the membrane protein of the different cell
      lines to which the nanoparticles are bound. Furthermore, a dependence on particle
      size is found for these interactions in the different cell lines. The results
      suggest that after optimization, this method could be used for gene transfection
      and gene therapy.

PMID- 16409078
TI  - Surface stress on the erythrocyte under laser irradiation with finite-difference
      time-domain calculation.
AB  - The surface stress on the real shape (biconcave disklike) of an erythrocyte under
      laser irradiation is theoretically studied according to the finite-difference
      time-domain (FDTD) method. The distribution of the surface stresses depends on
      the orientation of erythrocytes in the laser beam. Typically when the erythrocyte
      was irradiated from the side direction (the laser beam was perpendicular to the
      normal of the erythrocyte plane), the surface stresses were so asymmetrical and
      nonuniform that the magnitude of the surface stress on the back surface was three
      times higher than that on the front surface, and the highest-to-lowest ratio of
      the stress reached 16 times. For comparison, the surface stress was also
      calculated according to the ray optics (RO) method. The tendency of the stress
      distribution from the RO calculation was roughly similar to that of the FDTD
      method. However the RO calculation produced some unphysical results, such as the
      infinite stress on some surface region and the zero stress on the most parts of
      the erythrocyte surface, which is due to the neglecting of light diffraction. The
      results obtained from the FDTD calculation are believed quantitatively reliable,
      because the FDTD method automatically takes into account of the diffraction and
      interference effects of the light wave. Thus, the FDTD method is more suitable
      than the RO method for the stress study of erythrocytes.

PMID- 16409079
TI  - Selective targeting of the retinal pigment epithelium using an acousto-optic
      laser scanner.
AB  - Selective targeting of the retinal pigment epithelium (RPE) is a new strategy for
      treating certain retinal disorders while preserving adjacent photoreceptors. The
      treatment currently relies on a complex laser system to produce the required
      microsecond pulse structure. In our new approach, we scan the focus of a
      continuous-wave (cw) laser beam with acousto-optic deflectors to produce
      microsecond-long exposures at each RPE cell. Experiments were performed in vitro
      with a bench-top scanner on samples of young bovine RPE and in vivo on Dutch
      belted rabbits with a slit-lamp adapted scanner. Effective dose 50% (ED50) for
      RPE damage was determined in vitro by fluorescence cell viability assay and in
      vivo by fluorescein angiography. Damage to individual RPE cells was achieved with
      laser power on the order of 100 mW. Using separated scan lines, we demonstrate
      selectivity in the form of alternating lines of dead and surviving cells that
      resemble the scan pattern. Selectivity is also shown by the absence of retinal
      thermal coagulation in vivo. Selective RPE damage is feasible by rapidly scanning
      a cw laser beam. The scanning device is an attractive alternative to conventional
      laser coagulation and pulsed laser targeting of the RPE.

PMID- 16409080
TI  - Loss of image quality in photobleaching during microscopic imaging of fluorescent
      probes bound to chromatin.
AB  - Prolonged excitation of fluorescent probes leads eventually to loss of their
      capacity to emit light. A decrease in the number of detected photons reduces
      subsequently the resolving power of a fluorescence microscope. Adverse effects of
      fluorescence intensity loss on the quality of microscopic images of biological
      specimens have been recognized, but not determined quantitatively. We propose
      three human-independent methods of quality determination. These techniques
      require no reference images and are based on calculation of the actual resolution
      distance, information entropy, and signal-to-noise ratio (SNR). We apply the
      three measures to study the effect of photobleaching in cell nuclei stained with
      propidium iodide (PI) and chromomycin A3 (CA3) and imaged with fluorescence
      confocal microscopy. We conclude that the relative loss of image quality is
      smaller than the corresponding decrease in fluorescence intensity. Furthermore,
      the extent of quality loss is related to the optical properties of the imaging
      system and the noise characteristics of the detector. We discuss the importance
      of these findings for optimal registration and compression of biological images.

PMID- 16409081
TI  - Measuring microlymphatic flow using fast video microscopy.
AB  - Despite advances in the measurement of lymphatic function, little is known about
      the actual velocities of flow in microlymphatic ( approximately 100 mum diam)
      vessels. In this work, video microscopy and particle tracking methods are adapted
      and integrated with an ultra-high-speed imaging camera to obtain measurements of
      lymph velocities throughout the entire lymphatic contraction cycle in the
      ratmesentery, something that previous systems were incapable of measuring. To
      determine the system's accuracy, calibration experiments are conducted across the
      hypothesized physiologically significant range of velocities for microlymphatic
      flow (up to 15 mmsec). The system shows high accuracy, less than 2% error, when
      comparing actual with measured velocities. Microspheres flowing through 140-mum
      diam tubing are imaged to demonstrate the system's ability to determine flow
      rates in these small vessels by measuring particle velocities. To demonstrate
      biological applicability, mesenteric microlymphatics in loops of the small
      intestine of three male Sprague-Dawley rats are exteriorized and imaged with the
      high-speed system at a rate of 500 framessec for several contraction sequences.
      Lymph velocity fluctuates cyclically with the vessel wall contractions, ranging
      from -1 to 7 mmsec. These rates are higher than would be possible with standard
      video microscopy (3.75 mmsec maximum).

PMID- 16409082
TI  - Noninvasive measurement of cell volume changes by negative staining.
AB  - To maintain the intracellular concentration of ions and small molecules on
      osmotic challenges, nature has developed highly sophisticated transport systems
      for regulating water and ion content. An ideal measurement technique for volume
      changes of cells during osmotic challenges has to fulfil two requirements: it has
      to be osmotically inert, and it should allow online monitoring of cell volume
      changes. Here, a simple fluorescence microscopy-based approach is presented.
      Using fluorescein as a negative stain, it is possible to monitor cell volume
      changes without affecting the functionality of cell membranes and cell
      osmolarity. Measurement of Madine-Darby canine kidney (MDCK) cells after hypo-
      and hyperosmotic challenges reveals the main advantages of this approach: besides
      providing precise and reproducible quantitative data on reversible cell volume
      changes, the viability of the cells can be assessed directly by the appearance of
      stain in the cytoplasm. This becomes evident especially after hypo-osmotic
      challenge of glutaraldehyde-treated cells, which become leaky after fixation,
      followed by a massive volume change. This new approach represents a very
      sensitive measurement technique for cell volume changes resulting from water or
      ion flux, and thus seems to be an ideal tool for studying cell volume regulatory
      processes.

PMID- 16409083
TI  - Finite element analysis applied to cornea reshaping.
AB  - A 2-D finite element model of the cornea is developed to simulate corneal
      reshaping and the resulting deformation induced by refractive surgery. In the
      numerical simulations, linear and nonlinear elastic models are applied when
      stiffness inhomogeneities varying with depth are considered. Multiple simulations
      are created that employ different geometric configurations for the removal of the
      corneal tissue. Side-by-side comparisons of the different constitutive laws are
      also performed. To facilitate the comparison, the material property constants are
      identified from the same experimental data, which are obtained from mechanical
      tests on corneal strips and membrane inflation experiments. We then validate the
      resulting models by comparing computed refractive power changes with clinical
      results. Tissue deformations created by simulated corneal tissue removal using
      finite elements are consistent with clinically observed postsurgical results. The
      model developed provides a much more predictable refractive outcome when the
      stiffness inhomogeneities of the cornea and nonlinearities of the deformations
      are included in the simulations. Finite element analysis is a useful tool for
      modeling surgical effects on the cornea and developing a better understanding of
      the biomechanics of the cornea. The creation of patient-specific simulations
      would allow surgical outcomes to be predicted based on individualized finite
      element models.

PMID- 16409084
TI  - Determination of the complex refractive index of highly concentrated hemoglobin
      solutions using transmittance and reflectance measurements.
AB  - The complex refractive index of highly concentrated hemoglobin solutions as they
      appear in red blood cells are determined in the wavelength range of 250 to 1100
      nm using transmittance and Fresnel reflectance measurements. The determined real
      parts of the refractive indices are on average 0.02 units higher than the values
      found in the literature. The wavelength dependence of the measured data in the UV
      region differs from the calculated data using the Kramers-Kronig relation.

PMID- 16409085
TI  - Toward the discrimination of early melanoma from common and dysplastic nevus
      using fiber optic diffuse reflectance spectroscopy.
AB  - We describe a study of the discrimination of early melanoma from common and
      dysplastic nevus using fiber optic diffuse reflectance spectroscopy. Diffuse
      reflectance spectra in the wavelength range 550 to 1000 nm are obtained using 400
      microm core multimode fibers arranged in a six-illumination-around-one-collection
      geometry with a single fiber-fiber spacing of 470 microm. Spectra are collected
      at specific locations on 120 pigmented lesions selected by clinicians as possible
      melanoma, including 64 histopathologically diagnosed as melanoma. These locations
      are carried through to the histopathological diagnosis, permitting a spatially
      localized comparison with the corresponding spectrum. The variations in spectra
      between groups of lesions with different diagnoses are examined and reduced to
      features suitable for discriminant analysis. A classifier distinguishing between
      benign and malignant lesions performs with sensitivity/specificity of between
      6469% and 7278%. Classifiers between pairs of the group common nevus, dysplastic
      nevus, in situ melanoma, and invasive melanoma show better or similar performance
      than the benign/malignant classifier, and analysis provides evidence that
      different spectral features are needed for each pair of groups. This indicates
      that multiple discriminant systems are likely to be required to distinguish
      between melanoma and similar lesions.

PMID- 16409086
TI  - Simulating the response of terahertz radiation to basal cell carcinoma using ex
      vivo spectroscopy measurements.
AB  - Studies of basal cell carcinoma using terahertz pulsed imaging have revealed a
      significant difference between regions of tumor and healthy tissue. These
      differences are manifested in the reflected pulse due to what is thought to be
      changes in refractive index and absorption. We present measurements of the
      refractive index and absorption coefficient of excised normal tissue and basal
      cell carcinoma using terahertz (THz) transmission spectroscopy. We extract Debye
      parameters from these data and enter them into a finite difference time domain
      simulation to predict the shape of the waveforms reflected off the normal tissue
      and basal cell carcinoma and compare them with published in vivo data. Simulating
      the interaction of terahertz radiation with normal and cancerous tissue is a key
      step toward understanding the origin of contrast in terahertz images of skin
      cancer.

PMID- 16409087
TI  - Optoacoustic real-time dosimetry for selective retina treatment.
AB  - The selective retina treatment (SRT) targets retinal diseases associated with
      disorders in the retinal pigment epithelium (RPE). Due to the ophthalmoscopic
      invisibility of the laser-induced RPE effects, we investigate a noninvasive
      optoacoustic real-time dosimetry system. In vitro porcine RPE is irradiated with
      a Nd:YLF laser (527 nm, 1.7-micros pulse duration, 5 to 40 microJ, 30 pulses, 100
      Hz repetition rate). Generated acoustic transients are measured with a
      piezoelectric transducer. During 27 patient treatments, the acoustic transients
      are measured with a transducer embedded in an ophthalmic contact lens. After
      treatment, RPE damage is visualized by fluorescein angiographic leakage. Below
      the RPE damage threshold, the optoacoustic transients show no pulse-to-pulse
      fluctuations within a laser pulse train. Above threshold, fluctuations of the
      individual transients among each other are observed. If optoacoustic pulse-to
      pulse fluctuations are present, RPE leakage is observed in fluorescein
      angiography. In 96% of the irradiated areas, RPE leakage correlated with the
      optoacoustic defined threshold value. A noninvasive optoacoustic real-time
      dosimetry for SRT is developed and proved in vitro and during patient treatment.
      It detects the ophthalmoscopically invisible laser-induced damage of RPE cells
      and overcomes practical limitations of SRT for use in private practice.

PMID- 16409088
TI  - Atomic force-multi-optical imaging integrated microscope for monitoring molecular
      dynamics in live cells.
AB  - A novel hybrid imaging system is constructed integrating atomic force microscopy
      (AFM) with a combination of optical imaging techniques that offer high spatial
      resolution. The main application of this instrument (the NanoFluor microscope) is
      the study of mechanotransduction with an emphasis on extracellular matrix
      integrin-cytoskeletal interactions and their role in the cellular responses to
      changes in external chemical and mechanical factors. The AFM allows the
      quantitative assessment of cytoskeletal changes, binding probability, adhesion
      forces, and micromechanical properties of the cells, while the optical imaging
      applications allow thin sectioning of the cell body at the coverslip-cell
      interface, permitting the study of focal adhesions using total internal
      reflection fluorescence (TIRF) and internal reflection microscopy (IRM). Combined
      AFM-optical imaging experiments show that mechanical stimulation at the apical
      surface of cells induces a force-generating cytoskeletal response, resulting in
      focal contact reorganization on the basal surface that can be monitored in real
      time. The NanoFluor system is also equipped with a novel mechanically aligned
      dual camera acquisition system for synthesized Forster resonance energy transfer
      (FRET). The integrated NanoFluor microscope system is described, including its
      characteristics, applications, and limitations.

PMID- 16409090
TI  - Polarization-correlation mapping of biological tissue coherent images.
AB  - We investigate the statistical polarization parameters of biological tissue
      histological section images with different morphological structure. First we
      outline the results of polarization coordinate mapping and analysis of the
      statistics of the first to fourth orders of biological tissue image polarization
      azimuth and ellipticities. Second, we study the statistics of the first to fourth
      orders of coordinate distributions of the complex degree of mutual polarization
      (CDMP) of biological tissue images. Finally, we consider the diagnostic
      possibilities of investigating 2-D distributions of CDMP of images that
      correspond to physiologically normal and degeneratively and/or dystrophycally
      changed biological tissues that are being analyzed.

PMID- 16409089
TI  - Novel algorithm of processing optical coherence tomography images for
      differentiation of biological tissue pathologies.
AB  - A numerical algorithm based on a small-angle approximation of the radiative
      transfer equation (RTE) is developed to reconstruct scattering characteristics of
      biological tissues from optical coherence tomography (OCT) images. According to
      the algorithm, biological tissue is considered to be a layered random medium with
      a set of scattering parameters in each layer: total scattering coefficient,
      variance of a small-angle scattering phase function, and probability of
      backscattering, which fully describe the OCT signal behavior versus probing
      depth. The reconstruction of the scattering parameters is performed by their
      variation to fit the experimental OCT signal by the theoretical one using a time
      saving genetic algorithm. The proposed reconstruction procedure is tested on
      model media with known scattering parameters. The possibility to estimate
      scattering parameters from OCT images is studied for various regimes of OCT
      signal decay. The developed algorithm is applied to reconstruct optical
      characteristics of epithelium and stroma for normal cervical tissue and its
      pathologies, and the potential to distinguish between the types of pathological
      changes in epithelial tissue by its OCT images is demonstrated.

PMID- 16409092
TI  - Evaluation of enamel dental restoration interface by optical coherence
      tomography.
AB  - Evaluation of molar dental restorations on enamel is performed using optical
      coherence tomography (OCT) with 10 microm resolution. Images of approximately 50
      microm failure gaps in the restorations are demonstrated and the OCT images are
      compared with x-ray and optical microscopy pictures. The results demonstrate the
      potential of the technique for clinical evaluation of dental restorations.

PMID- 16409091
TI  - Diagnosis of meningioma by time-resolved fluorescence spectroscopy.
AB  - We investigate the use of time-resolved laser-induced fluorescence spectroscopy
      (TR-LIFS) as an adjunctive tool for the intraoperative rapid evaluation of tumor
      specimens and delineation of tumor from surrounding normal tissue. Tissue
      autofluorescence is induced with a pulsed nitrogen laser (337 nm, 1.2 ns) and the
      intensity decay profiles are recorded in the 370 to 500 nm spectral range with a
      fast digitizer (0.2 ns resolution). Experiments are conducted on excised
      specimens (meningioma, dura mater, cerebral cortex) from 26 patients (97 sites).
      Spectral intensities and time-dependent parameters derived from the time-resolved
      spectra of each site are used for tissue characterization. A linear discriminant
      analysis algorithm is used for tissue classification. Our results reveal that
      meningioma is characterized by unique fluorescence characteristics that enable
      discrimination of tumor from normal tissue with high sensitivity (>89%) and
      specificity (100%). The accuracy of classification is found to increase (92.8%
      cases in the training set and 91.8% in the cross-validated set correctly
      classified) when parameters from both the spectral and the time domain are used
      for discrimination. Our findings establish the feasibility of using TR-LIFS as a
      tool for the identification of meningiomas and enables further development of
      real-time diagnostic tools for analyzing surgical tissue specimens of meningioma
      or other brain tumors.

PMID- 16409093
TI  - Resonance Raman detection of carotenoid antioxidants in living human tissue.
AB  - Increasing evidence points to the beneficial effects of carotenoid antioxidants
      in the human body. Several studies, for example, support the protective role of
      lutein and zeaxanthin in the prevention of age-related eye diseases. If present
      in high concentrations in the macular region of the retina, lutein and zeaxanthin
      provide pigmentation in this most light sensitive retinal spot, and as a result
      of light filtering and/or antioxidant action, delay the onset of macular
      degeneration with increasing age. Other carotenoids, such as lycopene and beta
      carotene, play an important role as well in the protection of skin from UV and
      short-wavelength visible radiation. Lutein and lycopene may also have protective
      function for cardiovascular health, and lycopene may play a role in the
      prevention of prostate cancer. Motivated by the growing importance of carotenoids
      in health and disease, and recognizing the lack of any accepted noninvasive
      technology for the detection of carotenoids in living human tissue, we explore
      resonance Raman spectroscopy as a novel approach for noninvasive, laser optical
      carotenoid detection. We review the main results achieved recently with the Raman
      detection approach. Initially we applied the method to the detection of macular
      carotenoid pigments, and more recently to the detection of carotenoids in human
      skin and mucosal tissues. Using skin carotenoid Raman instruments, we measure the
      carotenoid response from the stratum corneum layer of the palm of the hand for a
      population of 1375 subjects and develop a portable skin Raman scanner for field
      studies. These experiments reveal that carotenoids are a good indicator of
      antioxidant status. They show that people with high oxidative stress, like
      smokers, and subjects with high sunlight exposure, in general, have reduced skin
      carotenoid levels, independent of their dietary carotenoid consumption. We find
      the Raman technique to be precise, specific, sensitive, and well suitable for
      clinical as well as field studies. The noninvasive laser technique may become a
      useful method for the correlation between tissue carotenoid levels and risk for
      malignancies or other degenerative diseases associated with oxidative stress.

PMID- 16409095
TI  - Correlation between clinical scoring of allergic patch test reactions and optical
      coherence tomography.
AB  - Noninvasive imaging techniques might be of particular diagnostic value for
      studying and monitoring cutaneous inflammatory conditions such as contact
      dermatitis. We evaluate acute allergic contact dermatitis (AACD) by means of
      optical coherence tomography (OCT) and correlate the clinical grading of patch
      test reactions with the findings obtained from OCT. Twenty positive patch test
      reactions (+, n = 6; ++, n = 7; +++, n = 7) are investigated using a conventional
      OCT scanner. In comparison to the control sites, OCT of AACD showed pronounced
      skin folds, thickened and/or disrupted entrance signals, and a significant
      increase in epidermal thickness. Moreover, clearly demarcated signal-free
      cavities within the epidermis and considerable reduction of dermal reflectivity
      are demonstrated by OCT. Notably, the latter findings strongly correlate with the
      clinical patch test grading. OCT may be a useful tool for visualization of
      micromorphological features of AACD. However, before OCT can be employed as an
      objective parameter in grading severity of patch test reactions, larger studies
      are required that correlate clinical patch test readings and OCT findings with
      histopathology.

PMID- 16409094
TI  - Biophysical effects of pulsed lasers in the retina and other tissues containing
      strongly absorbing particles: shockwave and explosive bubble generation.
AB  - Damage by pulsed lasers to the retina or other tissues containing strongly
      absorbing particles may occur through biophysical mechanisms other than simple
      heating. Shockwaves and bubbles have been observed experimentally, and depending
      on pulse duration, may be the cause of retinal damage at threshold fluence
      levels. We perform detailed calculations on the shockwave and bubble generation
      expected from pulsed lasers. For a variety of different laser pulse durations and
      fluences, we tabulate the expected strength of the shockwave and size of the
      bubble that will be generated. We also explain how these results will change for
      absorbing particles with different physical properties such as absorption
      coefficient, bulk modulus, or thermal expansion coefficient. This enables the
      assessment of biological danger, and possible medical benefits, for lasers of a
      wide range of pulse durations and energies, incident on tissues with absorbing
      particles with a variety of thermomechanical characteristics.

PMID- 16409096
TI  - Nanoscale internally referenced oxygen sensors produced from self-assembled
      nanofilms on fluorescent nanoparticles.
AB  - A novel sensor fabrication concept using indicators trapped in nanoengineered
      ultrathin films deposited on fluorescent nanoparticles is demonstrated for oxygen
      sensing. The nanoscale systems are based on the quenching of tris(4,7-diphenyl
      1,10-phenanthroline)ruthenium(II) immobilized within polyelectrolyte multilayers
      deposited on the surface of nanoparticle templates. The ionically bound nanofilms
      create a porous scaffold into which controlled precipitation of the chromophore
      is achieved using a combination of electrostatic attraction and dye insolubility
      in water. The fluorescent nanoparticles act as physical scaffolds and also
      provide a complementary spectral signature for use as an internal intensity
      reference. Oxygen sensors created on 100-nm yellow-green fluorescent particles
      exhibit a linear Stern-Volmer behavior with a quenching constant of 1.06 mM and
      sensitivity of 60%, which demonstrates that the dye is still partially accessible
      to oxygen following immobilization. To demonstrate the feasibility of
      intracellular metabolic monitoring with such nanoprobes, the oxygen sensors were
      chemically delivered into human dermal fibroblasts with no apparent loss in cell
      viability. The results prove that the approach to sensor production is facile and
      leads to sensitive systems that can be further optimized for improved response,
      and these findings support the further development of similar self-referenced
      probes toward quantitative intracellular analysis.

PMID- 16409097
TI  - Reevaluation of near-infrared light propagation in the adult human head:
      implications for functional near-infrared spectroscopy.
AB  - Using both experimental and theoretical methods, we examine the contribution of
      different parts of the head to near-IR (NIR) signal. Time-resolved spectroscopy
      is employed to measure the mean optical path length (PL), and the absorption
      (mu(a)) and reduced scattering (mu(s)') coefficients in multiple positions of the
      human head. Monte Carlo simulations are performed on four-layered head models
      based on an individual magnetic resonance imaging (MRI) scan to determine mu(a)
      and mu(s)' in each layer of the head by solving inverse problems, and to estimate
      the partial path length in the brain (p-PL) and the spatial sensitivity to
      regions in the brain at the source-detector separation of 30 mm. The PL is
      closely related to the thickness of the scalp, but not to that of other layers of
      the head. The p-PL is negatively related to the PL and its contribution ratio to
      the PL is 5 to 22% when the differential path length factor is 6. Most of the
      signal attributed to the brain comes from the upper 1 to 2 mm of the cortical
      surface. These results indicate that the NIR signal is very sensitive to
      hemodynamic changes associated with functional brain activation in the case that
      changes in the extracerebral tissue are ignorable.

PMID- 16409098
TI  - Effect of tissue preservation on imaging using ultrahigh resolution optical
      coherence tomography.
AB  - Ultrahigh resolution optical coherence tomography (OCT) is an emerging imaging
      modality that enables noninvasive imaging of tissue with 1- to 3-microm
      resolutions. Initial OCT studies have typically been performed using harvested
      tissue specimens (ex vivo). No reports have investigated postexcision tissue
      degradation on OCT image quality. We investigate the effects of formalin fixation
      and commonly used cell culture media on tissue optical scattering characteristics
      in OCT images at different times postexcision compared to in vivo conditions. OCT
      imaging at 800-nm wavelength with 1.5-mum axial resolution is used to image the
      hamster cheek pouch in vivo, followed by excision and imaging during preservation
      in phosphate-buffered saline (PBS), Dulbecco's Modified Eagle's Media (DMEM), and
      10% neutral-buffered formalin. Imaging is performed in vivo and at sequential
      time points postexcision from 15 min to 10 to 18 h. Formalin fixation results in
      increases in scattering intensity from the muscle layers, as well as shrinkage of
      the epithelium, muscle, and connective tissue of approximately 50%. PBS
      preservation shows loss of optical contrast within two hours, occurring
      predominantly in deep muscle and connective tissue. DMEM maintains tissue
      structure and optical scattering characteristics close to in vivo conditions up
      to 4 to 6 h after excision and best preserved tissue optical properties when
      compared to in vivo imaging.

PMID- 16409099
TI  - Optical coherence tomography speckle reduction by a partially spatially coherent
      source.
AB  - Speckle in optical coherence tomography (OCT) images originates in the high
      spatial coherence of incident light that enables interference of light
      backscattered from spatially heterogenous tissue specimens. We report results of
      a numerical simulation and an experiment to test speckle reduction using a
      partially spatially coherent source. A Gaussian-Schell model for a partially
      spatially coherent source is used in the OCT simulation. For the experiment, such
      a source was generated by a spatially coherent boardband light source and a
      multimode fiber. The advantage of using a multimode fiber in combination with a
      broadband source is the large number of photons per coherence volume. To
      illustrate speckle reduction with a partially spatially coherent source, we
      record low-coherence interferograms of a scattering surface using single-mode and
      multimode source fibers. Interferograms recorded using a single-mode source fiber
      are indicative of those observed using conventional OCT. Speckle in OCT images
      recorded using a multimode source fiber is substantially reduced.

PMID- 16409100
TI  - Optically tunable nanoparticle contrast agents for early cancer detection: model
      based analysis of gold nanoshells.
AB  - Many optical diagnostic approaches rely on changes in scattering and absorption
      properties to generate optical contrast between normal and diseased tissue.
      Recently, there has been increasing interest in using exogenous agents to enhance
      this intrinsic contrast with particular emphasis on the development for targeting
      specific molecular features of disease. Gold nanoshells are a class of core-shell
      nanoparticles with an extremely tunable peak optical resonance ranging from the
      near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a
      wide variety of core and shell sizes can easily be fabricated to scatter and/or
      absorb light with optical cross sections often several times larger than the
      geometric cross section. Using gold nanoshells of different size and optical
      parameters, we employ Monte Carlo models to predict the effect of varying
      concentrations of nanoshells on tissue reflectance. The models demonstrate the
      importance of absorption from the nanoshells on remitted signals even when the
      optical extinction is dominated by scattering. Furthermore, because of the strong
      optical response of nanoshells, a considerable change in reflectance is observed
      with only a very small concentration of nanoshells. Characterizing the optical
      behavior of gold nanoshells in tissue will aid in developing nanoshells as
      contrast agents for optical diagnostics.

PMID- 16409101
TI  - Tissue phantom for optical diagnostics based on a suspension of microspheres with
      a fractal size distribution.
AB  - We demonstrate experimentally the possibility of reproducing the phase function,
      absorption, and scattering coefficients of a real biological tissue (adult brain
      white matter and liver) using a suspension of polystyrene microspheres with a
      fractal size distribution. The design of a light scattering goniometer with a
      cylindrical cell in air is discussed, and phase function measurements using the
      device are described. The scattering coefficient is measured using transmission
      spectrophotometry and the absorption and reduced scattering coefficients are
      measured using a time-resolved method. A good match between real tissue and
      phantom parameters is demonstrated.

PMID- 16409102
TI  - Effect of size of TiO2 nanoparticles embedded into stratum corneum on ultraviolet
      A and ultraviolet-B sun-blocking properties of the skin.
AB  - Recently there has been a strong demand to protect human skin against negative
      effects of the UV solar light. This problem is interesting due to the increased
      frequency of human diseases caused by such radiation. We aim to evaluate how the
      optical properties of the horny layer of skin can be effectively changed by
      imbedding TiO2 fine particles to achieve the maximal attenuation of the UV solar
      radiation. In-depth distribution of TiO2 particles embedded into the skin by
      multiple administration of sunscreens is determined experimentally using the tape
      stripping technique. A computer code implementing the Monte Carlo method is
      developed to simulate photon migration within the 20-microm-thick horny layer
      filled with nanosized TiO2 spheres, 25 to 200 nm in diameter. Dependencies of the
      UV radiation of two wavelengths (310 and 400 nm) absorbed by and totally
      reflected from, as well as transmitted through the horny layer on the size of
      TiO2 particles are obtained and analyzed. The most attenuating particles are
      found to be 62 and 122 nm in diameter for 310- and 400-nm light, respectively.
      The former could be suggested as the main fraction to be used in sunscreens to
      prevent erythema.

PMID- 16409103
TI  - Fast three-dimensional laser scanning scheme using acousto-optic deflectors.
AB  - A scheme for fast 3-D laser scanning using acousto-optic deflectors is proposed
      and demonstrated. By employing counterpropagating acoustic waves that are both
      chirped and offset in their frequencies, we show that it is possible to
      simultaneously scan both axially and laterally with frame rates on the order of
      tens of kilohertz. This scheme was specifically designed for application with
      multiphoton imaging, particularly of neurons, where it will enable the concurrent
      monitoring of physiological signals at multiple locations within a microscopic 3
      D volume (350 x 350 x 200 microm). When used for this purpose, we demonstrate how
      this scheme would also inherently compensate for spatial dispersion when
      ultrafast laser pulses are used in acousto-optic multiphoton microscopy.

PMID- 16409104
TI  - Measurements and quality assessments of near-infrared plasma glucose spectra in
      the combination band region using a scanning filter spectrometer.
AB  - Near-infrared measurements of glucose in human plasma are performed using a
      custom, rapid, high-throughput filter-based spectrometer covering a spectral
      range between 2080 and 2315 nm. Quality of the measured glucose signals is
      quantified through the use of two figures of merit: selectivity and limit of
      detection. Selectivity measures the uniqueness of the glucose spectrum from among
      the interfering spectra. Limit of detection measures the smallest glucose
      concentration change detectable. The proposed system, which includes the
      spectroscopic hardware and a spectral preprocessing algorithm, is shown to
      produce a selectivity value of 0.57, with zero being nonselective and one being
      fully selective, and a limit of detection value of 2.2 mM. Prediction of an
      independent dataset is also performed using net analyte signal-based and partial
      least-squares multivariate calibration techniques, which produce standard error
      of prediction values of 1.14 and 1.45 mM, respectively.

PMID- 16409108
TI  - Differences in management of older women influence breast cancer survival:
      results from a population-based database in Sweden.
AB  - BACKGROUND: Several reports have shown that less aggressive patterns of
      diagnostic activity and care are provided to elderly breast carcinoma patients.
      We sought to investigate whether differences in the management of older women
      with breast cancer are associated with survival. METHODS AND FINDINGS: In an
      observational study using a population-based clinical breast cancer register of
      one health-care region in Sweden, we identified 9,059 women aged 50-84 y
      diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative
      survival ratio was estimated for patients classified by age group, diagnostic
      activity, tumor characteristics, and treatment. The 5-y relative survival for
      breast cancer patients was lower (up to 13%) in women 70-84 y of age compared to
      women aged 50-69 y, and the difference was most pronounced in stage IIB-III and
      in the unstaged. Significant differences in disease management were found, as
      older women had larger tumors, had fewer nodes examined, and did not receive
      treatment by radiotherapy or by chemotherapy as often as the younger women.
      Adjustment for diagnostic activity, tumor characteristics, and treatment
      diminished the relative excess mortality in stages III and in the unstaged,
      whereas the excess mortality was only marginally affected in stage IIB.
      CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later
      diagnosis in older women are associated with poorer survival. The large
      differences in treatment of older women are difficult to explain by co-morbidity
      alone.

PMID- 16409109
TI  - Ergovaline movement across Caco-2 cells.
AB  - Ergovaline's role in the direct causation of fescue toxicosis first requires
      establishment of its dietary absorption. Therefore, ergovaline movement across
      human intestinal cells was assessed using Caco-2 cells derived from human colon
      carcinoma. A pre-equilibrated mixture of ergovaline/ergovalinine (60:40 ratio of
      isomers) was added to the apical compartment, and isomer movements were assessed
      by high-performance liquid chromatography (HPLC) of extracted media (initial pre
      isomerized ergovaline concentrations of 6 and 22 microM, two doses). Mathematical
      models for ergot alkaloid movement were developed. Rates of movement were not
      different for the isomers. In the absence of cells, basal accumulation of isomers
      was essentially linear for 3 h regardless of loading concentration, after which
      basal accumulation of ergovaline/ergovalinine plateaued. Rates of
      ergovaline/ergovalinine movement in the presence of cells slowed to about 25% the
      rate of movement in the absence of cells (22 microM, kt = 0.0133 no cells, 0.0036
      with cells, P < 0.05). Mass transfer rate was 7.5 ng x cm(-2) x min(-1) and was
      similar to that reported for ergovaline using a parabiotic chamber with sheep
      omasum. After 6 h in the presence of cells, approximately 25 and 40% of the total
      ergovaline/ergovalinine administered had accumulated in the basal compartment for
      6.6 and 22 microM treatments, respectively. Ergovaline and its naturally
      occurring isomer, ergovalinine, readily crossed intestinal cells intact and at
      similar rates. Either isomer, or a combination of both, could be involved in the
      pathogenesis of fescue toxicosis at sites distal to the intestine.

PMID- 16409110
TI  - Influence of serum on adult and fetal dermal fibroblast migration, adhesion, and
      collagen expression.
AB  - The wound healing response to injury can be affected by many factors such as cell
      migration and extracellular matrix elaboration. The objective of this study was
      to examine the serum- and age-dependent effects on cell migration, adhesion, and
      collagen expression by skin fibroblasts. Dermal fibroblasts were isolated and
      plated with and without serum for up to 7 d. Cell migration was determined by
      quantitative image analysis, adhesion was quantified using a centrifugation
      assay, and collagen expression was assessed by PCR and immunohistochemical
      staining. Both adult and fetal fibroblasts migrated significantly faster in serum
      containing medium compared to serum-free medium. There was no significant
      difference in migration between the two cell types in either serum-containing or
      serum-free medium. There was no significant difference in adhesion in the
      presence of serum, although there was a greater fraction of adherent fetal skin
      fibroblasts than adult fibroblasts in serum-free medium. Moreover, the adherent
      fraction of fetal fibroblasts in serum-free medium was not significantly
      different from that in serum-containing medium, suggesting that fetal skin
      fibroblasts possess serum-independent adhesion properties. Collagen mRNA
      expression was significantly up-regulated in serum-free compared to serum
      containing medium for both cell types. With respect to collagen
      immunohistochemistry, both dermal fibroblast populations exhibited greater type I
      collagen compared to type III collagen staining. Quantitative assessment of
      collagen staining indicated significantly enhanced type I collagen secretion in
      the presence of serum by fetal skin fibroblasts. These findings suggest that
      intrinsic cellular characteristics may govern the observed differences in adult
      and fetal wound healing.

PMID- 16409111
TI  - Viability of glycerol-preserved and cryopreserved anuran skin.
AB  - Anurans are important animal models for studying the effects of anthropogenic
      chemical contamination of the environment. Two-compartment Teflon flow-through
      diffusion cells can be used to study percutaneous absorption of xenobiotics
      across harvested skin. However, such an approach currently necessitates that skin
      be harvested just before experimentation, a requirement that calls for the
      continuous growth and housing of living animals. The ability to preserve and
      store skin would allow more efficient use of animals and more flexibility in
      experimental design. To this end, we examined the viability of harvested anuran
      skin stored under various protocols consistent with current practices of
      mammalian skin preservation. Skin from the American bullfrog maintained 80-85%
      viability after 28 d, whereas viability of skin from the marine toad was only
      maintained for 7-10 d.

PMID- 16409112
TI  - Effect of overexpression of estrogen receptors in osteoblasts.
AB  - Our study focused on investigating the mechanism of action of estrogen in
      regulating p53 levels within osteoblasts. In the studies reported here, we
      attempted to understand the role of estrogen receptors, ER-alpha and ER-beta, in
      the regulation of p53 and osteoblast differentiation. We stably expressed ER
      alpha and ER-beta in ROS 17/2.8 cells and isolated several single cell clones.
      These clones were initially characterized for expression of the exogenous
      receptors, and representative clones from each type were chosen for further
      analyses. Cell proliferation, alkaline phosphatase activity, and the viability of
      these clones in culture were tested. The cells expressing exogenous ER-alpha
      exhibited more differentiated characteristics than cells expressing ER-beta.
      Morphologically, ER-beta-overexpressing cells were more rounded than the ER-alpha
      overexpressing cells, which were more elongated and fibroblastic in appearance.
      The ER-beta-expressing cells had a higher survival and growth rate when compared
      with ER-alpha cells. The ER-alpha clones were not as viable as ER-beta clones,
      and some of the ER-alpha cell lines showed signs of senescence, with an increase
      in senescence-associated (SA) galactosidase activity. The basal levels of p53
      functional activity were higher in cells expressing ER-alpha as was protein
      expression of the p53-regulated gene p21. The significance of these receptors to
      osteoblast differentiation and p53 regulation is discussed.

PMID- 16409113
TI  - Pronuclear synchronization and nuclear morphology of mature and in vitro matured
      oocytes in the rat: an ultrastructural study.
AB  - The objective of this study was to evaluate synchronous and asynchronous
      pronucleus (PN) formation and the related patterns of juxtapositional nucleolus
      (n) formation in immature (prophase I [PI] and metaphase I [MI]) and mature
      (metaphase II [MII]) oocytes after fertilization, both ultrastructurally and at
      the level of light microscope. A single dose of 15 IU gonadotrophin was injected
      subcutaneously to twenty four 26-wk-old, female Wistar rats to induce ovulation.
      Human chorionic gonadotrophin (4 IU) was administered 40 h later, and after 4-6 h
      the ovaries were dissected, and the oocytes were aspirated. A total of 214 rat
      oocytes were classified according to a maturation index as follows: group I, 80
      PI oocytes; group II, 50 MI oocytes; and group III, 84 MII oocytes. Immature
      oocytes were in vitro matured for 18-36 h. Spermatozoa were acquired by
      microepididymal sperm aspiration and processed using swim-up technique.
      Intracytoplasmic sperm injection was performed on mature oocytes after 2 h of
      incubation and on in vitro matured (IVM) oocytes 4 h after maturation. Pronuclear
      synchronization [both pronucleases (PNs) centrally located, equal sized, with
      equal numbers and sizes of juxtapositional nucleoli (Nn)] was observed in
      fertilized oocytes. Asynchronous PN formation (diversity between male and female
      PNs, related to dimensions, localization, and the number of Nn) in groups I, II,
      and III was found in 75, 86, and 47% of preembryos, respectively. There was a
      significant difference of synchronous pronuclear formation between mature and IVM
      oocytes (P < 0.05). In IVM oocytes, asynchronous PN formation is high, and
      juxtapositional pronucleolar patterns are observed to be low by transmission
      electron microscope (TEM).

PMID- 16409114
TI  - Multicolor karyotype analyses of mouse embryonic stem cells.
AB  - The manipulation of embryonic stem (ES) cells to introduce directional genetic
      changes into the genome of mice has become an important tool in biomedical
      research. Monitoring of cell morphology before and after DNA manipulation and
      special culture conditions are a prerequisite to preserve the pluripotent
      properties of ES cells and thus their ability to generate chimera and effective
      germline transmission (GLT). It has been reported that prolonged cell culturing
      may affect the diploid chromosomal composition of cells and therefore the
      percentage of chimerism and GLT. Herein, we report multicolor-fluorescence in
      situ hybridization (M-FISH) analysis of four different ES cell lines/clones.
      Although the morphology of all four ES cell lines/clones appeared normal and all
      four expressed the early markers Oct-3/4 and Nanog, two cell lines presented
      consistent numerical and structural chromosome aberrations. We demonstrate that M
      FISH is a sensitive and accurate method for a comprehensive karyotype analysis of
      ES cells and may minimize time, costs, and disappointments due to inadequate ES
      cell sources.

PMID- 16409116
TI  - Properties of a unique mutant of Helicoverpa armigera single-nucleocapsid
      nucleopolyhedrovirus that exhibits a partial many polyhedra and few polyhedra
      phenotype on extended serial passaging in suspension cell cultures.
AB  - Serial passaging of wild-type Helicoverpa armigera single-nucleocapsid
      nucleopolyhedrovirus (HaSNPV) in H. zea (Hz-AM1) insect cell cultures results in
      rapid selection for the few polyhedra (FP) phenotype. A unique HaSNPV mutant
      (ppC19) was isolated through plaque purification that exhibited a partial many
      polyhedra (MP) and FP phenotype. On serial passaging in suspension cell cultures,
      ppC19 produced fivefold more polyhedra than a typical FP mutant (FP8AS) but
      threefold less polyhedra than the wild-type virus. Most importantly, the
      polyhedra of ppC19 exhibited MP-like virion occlusion. Furthermore, ppC19
      produced the same amount of budded virus (BV) as the FP mutant, which was
      fivefold higher than that of the wild-type virus. This selective advantage was
      likely to explain its relative stability in polyhedra production for six passages
      when compared with the wild-type virus. However, subsequent passaging of ppC19
      resulted in a steep decline in both BV and polyhedra yields, which was also
      experienced by FP8AS and the wild-type virus at high passage numbers. Genomic
      deoxyribonucleic acid profiling of the latter suggested that defective
      interfering particles (DIPs) were implicated in this phenomenon and represented
      another undesirable mutation during serial passaging of HaSNPV. Hence, a strategy
      to isolate HaSNPV clones that exhibited MP-like polyhedra production but FP-like
      BV production, coupled with low multiplicities of infection during scale-up to
      avoid accumulation of DIPs, could prove commercially invaluable.

PMID- 16409115
TI  - Effect of exogenous wild-type p53 on melanoma cell death pathways induced by
      irradiation at different linear energy transfer.
AB  - We investigated the effect of exogenous wild-type p53 on the radiation-induced
      cells apoptosis and necrosis at different levels of linear energy transfer (LET)
      to evaluate its mechanisms. The human melanoma cell line A375, which bears wild
      type p53 gene status, was used, as well as the transfectant A375 cells (A375/p53)
      with adenoviral vector containing the wild-type p53 gene. We exposed these cells
      to X-rays and to accelerated carbon-ion (C-) beams. Cellular sensitivities were
      determined by using clonogenic assay. Apoptotic and necrotic cell deaths were
      determined morphologically by dual staining (acridine orange and ethidium
      bromide) using fluorescence microscopy. We discovered that (1) there was no
      significant difference in survival fraction between A375 cells and A375/p53 cells
      irradiated by C-beams with greater than 32 KeV/microm LET, (2) although apoptosis
      in the two kinds of cells increased in an LET-dependent manner, exogenous wild
      type P53 induced cell apoptosis efficiently in A375/p53 relative to A375 cells
      with X-rays or high-LET irradiation, and (3) by high-LET irradiation, the number
      of necrosis in A375 cells increased significantly (P < 0.05) in comparison with
      A375/p53 cells. These results indicate that in high-LET irradiation apoptosis
      induction is p53 dependent partly and exogenous wild-type P53 plays an important
      role in modulating cell death type, although there was no significant difference
      in cellular radiosensitivities. Our observation in the study offers the potential
      application of high-LET radiation combined with p53 in the management of human
      patients with melanoma.

PMID- 16409117
TI  - AcMNPV in permissive, semipermissive, and nonpermissive cell lines from
      Arthropoda.
AB  - Insect cell lines from Arthropoda represented by Lepidoptera, Coleoptera,
      Diptera, and Homoptera were evaluated for their ability to support replication of
      AcMNPV. In addition, some of the cell lines that were refractive to AcMNPV were
      tested with AcMNPV hsp70 Red, a recombinant carrying the red fluorescent protein
      (RFP) gene, for their ability to express this protein after inoculation. Of the
      10 lepidopteran cell lines tested, only three cell lines from Helicoverpa zea
      (BCIRL-HZ-AM1), Lymantria dispar (IPLB-LD 65), and Cydia pomonella (CP-169)
      failed to support detectable viral replication as measured by tissue culture
      infectious dose 50 (TCID50) assay. Heliothis virescens (BCIRL-HV-AM1) produced
      the highest viral titer of 2.3 +/- 0.1 x 10(7) TCID50/ml followed by Heliothis
      subflexa (BCIRL-HS-AM1) at 4.7 +/- 0.1 x 10(6) TCID50/ml and Spodoptera
      frugiperda (IPLB-SF21) at 4.1 +/- 0.1 x 10(6) TCID50/ml. None of the coleopteran,
      dipteran, or homopteran cell lines supported AcMNPV replication. However, when
      studies were performed using AcMNPV hsp70 Red, the dipteran cell lines Aedes
      aegypti (ATC-10) and Drosophila melanogaster (line 2), both expressed the RFP as
      well as the refractive lepidopteran cell lines from H. zea and L. dispar. No RFP
      expression was observed in any of the coleopteran or homopteran cell lines. Cell
      lines refractive to AcMNPV did not appear to be adversely affected by the virus,
      as judged by their ability to multiply, nor was there any indication of induced
      apoptosis, as assessed by deoxyribonucleic acid fragmentation profiles or cell
      blebbing, or both.

PMID- 16409118
TI  - Effects of hepatocyte growth factor and platelet-derived growth factor on the
      repair of meniscal defects in vitro.
AB  - Injuries to the avascular region of the meniscus occur frequently and may be
      difficult to repair. This study was designed to determine whether growth factors
      could diffuse from a collagen sponge or a collagen gel into meniscal tissue and
      stimulate healing of defects using an in vitro model. The diffusion of platelet
      derived growth factor (PDGF) from the collagen carriers into the medium was rapid
      with approximately 50% being released from the collagen sponge within the first
      hour. After 5 d of incubation, 8% of the PDGF was present in the meniscus, 11% in
      the collagen sponge, and 62% had been released into the medium. Similar results
      were obtained when a collagen gel was used as a carrier. Histological evaluation
      of the meniscal explants after 2 wk in culture revealed extensive proteoglycan
      staining in the areas surrounding defects treated with either hepatocyte growth
      factor (HGF) or PDGF compared with controls without growth factor. The HGF-PDGF
      treatment resulted in alignment and migration of meniscal cells toward the
      defect, which was not observed in untreated controls. At 3-7 d, increased number
      of cells were observed in defects treated with collagen gels (but not the sponge)
      with PDGF-HGF. At 4 wk, combined HGF-PDGF treatment resulted in the formation of
      tissue with birefringence by polarized microscopy, suggestive of organized
      collagen. The data suggest that use of specific PDGF-HGF may enhance the repair
      of meniscal injuries.

PMID- 16409120
TI  - Lentivirus-mediated gene transfer to the central nervous system: therapeutic and
      research applications.
AB  - The management of disorders of the nervous system remains a medical challenge.
      The key goals are to understand disease mechanisms, to validate therapeutic
      targets, and to develop new therapeutic strategies. Viral vector-mediated gene
      transfer can meet these goals and vectors based on lentiviruses have particularly
      useful features. Lentiviral vectors can deliver 8 kb of sequence, they mediate
      gene transfer into any neuronal cell type, expression and therapy are sustained,
      and normal cellular functions in vitro and in vivo are not compromised. After
      delivery into the nervous system they induce no significant immune responses,
      there are no unwanted side effects of the vectors per se to date, and
      manufacturing and safety testing for clinical applications are well advanced.
      There are now numerous examples of effective long-term treatment of animal models
      of neurological disorders, such as Parkinson's disease, Alzheimer's disease,
      Huntington's disease, motor neuron diseases, lysosomal storage diseases, and
      spinal injury, using a range of therapeutic genes expressed in lentiviral
      vectors. Significant issues remain in some areas of neural gene therapy including
      defining the optimum therapeutic gene(s), increasing the specificity of delivery,
      regulating expression of potentially toxic genes, and designing clinically
      relevant strategies. We discuss the applications of lentiviral vectors in therapy
      and research and highlight the essential features that will ensure their
      translation to the clinic in the near future.

PMID- 16409121
TI  - Adeno-associated virus types 5 and 6 use distinct receptors for cell entry.
AB  - The transduction efficiency of adeno-associated virus (AAV) vectors in various
      somatic tissues is determined primarily by the viral capsid proteins. In contrast
      to vectors made with AAV type 2 capsids, those having type 5 or 6 capsids show
      high transduction rates in airway epithelial cells, in a range that should be
      sufficient for treating lung disease. Here we have compared the properties of
      vectors made with AAV5 or AAV6 capsid proteins to determine whether their
      receptor usage is similar, and found several differences between the viruses.
      First, an AAV6 vector did not hemagglutinate red blood cells, whereas an AAV5
      vector did, and this property was sialic acid dependent. Second, AAV5 vector
      transduction required sialic acid in all cells tested, whereas AAV6 vector
      transduction was sialic acid dependent or independent, depending on the target
      cells tested. Third, levels of an AAV6 vector that interfered with entry of
      another AAV6 vector only poorly inhibited AAV5 vector transduction and vice
      versa. These results indicate that AAV5 and AAV6 vectors use distinct cellular
      receptors for cell entry. Although both AAV5 and AAV6 vectors exhibited high
      transduction rates in well-differentiated human airway epithelial cultures, they
      exhibited distinct cell-type transduction profiles in mouse lung that may reflect
      differences in receptor usage.

PMID- 16409122
TI  - Treatment of schwannomas with an oncolytic recombinant herpes simplex virus in
      murine models of neurofibromatosis type 2.
AB  - Gene therapy for schwannomas was evaluated in two mouse models of
      neurofibromatosis type 2 (NF2): (1) a transgenic model in which mice express a
      dominant mutant form of merlin and spontaneously develop schwannomas, and (2) a
      xenograft model in which human schwannoma tissue is implanted subcutaneously into
      immune- compromised mice. In both models, schwannoma volumes were monitored by
      magnetic resonance imaging (MRI) and showed strong gadolinium enhancement typical
      of these tumors in humans. Both types of tumor were positive for the Schwann cell
      marker S100, and highly infectable with herpes simplex virus (HSV) vectors.
      Schwannomas were injected with an oncolytic HSV-1 recombinant virus vector,
      G47Delta, which has deletions in genes for ribonucleotide reductase (ICP6),
      gamma34.5, and ICP47. In the NF2 transgenic model, schwannomas were reduced by
      more than half their original size by 10 days after infection. In the case of
      subcutaneous schwannoma xenografts, reduction in size after infection occurred
      more slowly, with a mean reduction of onethird by 42 days after treatment.
      Schwannomas injected with control vehicles continued to grow slowly over time in
      both schwannoma models. These studies demonstrate the ability of an oncolytic
      recombinant HSV vector to reduce the volume of schwannoma tumors in NF2 tumor
      models in mice and extend the possible therapeutic applications of oncolytic
      vectors for benign tumors to reduce mass while minimizing nerve damage.

PMID- 16409123
TI  - Intravenous and isolated limb perfusion delivery of wild type and a tumor
      selective replicating mutant vaccinia virus in nonhuman primates.
AB  - In this study we examine the safety, feasibility, and biodistribution of a tumor
      selective mutant vaccinia (vvDD) and wild-type WR (vF13) vaccinia after delivery
      via intradermal or intravenous infection or isolated limb perfusion (ILP) in
      rhesus macaques. By intradermal inoculation, 10(6) PFU of vvDD caused a minimal
      skin reaction whereas vF13 caused marked erythema and necrosis with a peak
      indurated area of 108 cm2. By intravenous delivery, vvDD caused no clinical
      symptoms of viremia and no viral recovery from tissues, serum, saliva, urine, or
      feces. In contrast, vF13 caused symptoms of lethargy, anorexia, fever, and signs
      of viremia. Delivery of vF13 via ILP resulted in numerous cutaneous pox lesions
      localized solely to the perfused limb with high viral recovery in the perfused
      skin and muscle. ILP with vvDD resulted in no visible pox lesions and no clinical
      signs or symptoms of viremia. No long-term toxicity was identified after ILP with
      10(9) PFU of vvDD, and no virus was recovered from any tissue, serum, saliva,
      urine, or fecal sample. These results suggest that vvDD appears to be safe in
      primates, and thus vvDD should be further investigated for clinical trial in
      human cancer patients.

PMID- 16409124
TI  - Efficient AAV1-AAV2 hybrid vector for gene therapy of hemophilia.
AB  - Adeno-associated virus (AAV) serotype 1 (AAV1) has been shown to be more
      effective than the well-studied AAV serotype 2 (AAV2) in muscle gene transfer.
      Replacement of amino acids 350 to 430 of AAV2 VP1 with the corresponding amino
      acids from VP1 of AAV1 resulted in a hybrid vector, termed AAV-221-IV, which
      behaved similarly to AAV1 in vitro and in vivo in muscle. Intramuscular injection
      of 1x10(11) vector particles per mouse of hybrid vector carrying a human FIX
      transgene in CD4 knockout mice resulted in an average level of human FIX in the
      plasma of 450 ng/ml, 4- to 10-fold higher than in mice injected with an AAV2
      vector carrying the same transgene, and 80% of the transgene levels in animals
      treated with the same dose of AAV1. DNA analysis of injected muscle showed a 10
      fold higher copy number after gene delivery by the hybrid vector compared with
      AAV2. A comparison of total DNA versus DNA from intact virus particles suggests a
      higher stability of hybrid virus particles. These results suggest that changes in
      the AAV capsid have an effect on virus-cell receptor interaction, and also
      influence trafficking and processing of the virus particle in the cell. This
      "hybrid vector" retains the heparin-binding sites of AAV2 and, therefore, can be
      purified by passage through a heparin-Sepharose column with the same efficiency
      as AAV2. When tested in vivo, either in CD4 knockout mice or in a hemophilic
      mouse model, the heparin-purified hybrid vector showed >10-fold higher activity
      than similarly purified AAV2. This demonstrates the utility of this hybrid vector
      in the performance of large-scale heparin column purification to generate a
      vector with a high expression profile for muscle-directed gene delivery.
      Initiation of clinical studies with this hybrid vector may be facilitated because
      it differs from AAV2 by only nine amino acids.

PMID- 16409125
TI  - Novel three-pronged strategy to enhance cancer cell killing in glioblastoma cell
      lines: histone deacetylase inhibitor, chemotherapy, and oncolytic adenovirus
      dl520.
AB  - Resistance to radiation and chemotherapy remains an obstacle to the treatment of
      brain tumors. We have demonstrated that the replication-deficient adenovirus
      d1520, which lacks the E1A 13S protein, replicates efficiently and exhibits
      oncolytic potential in multidrug-resistant cells with nuclear localization of the
      human transcription factor YB-1. However, besides others, key factors regarding
      oncolytic virotherapy are limited tumor transduction rate and low replication
      efficiency. The objective of this study was to determine whether the
      chemotherapeutic agent irinotecan, by enhancing nuclear localization of YB-1, and
      the histone deacetylase inhibitor trichostatin A, by upregulating coxsackievirus
      adenovirus receptor (CAR) expression, could augment replication of and cell lysis
      by adenovirus dl520 in glioblastomas in vitro. We found that trichostatin A
      upregulated CAR expression and that irinotecan caused increased nuclear
      localization of YB-1 in both glioblastoma cell lines. Irinotecan alone, and
      trichostatin A alone, enhanced replication of and cell lysis by dl520.
      Importantly, when combining both agents, the replication efficiency (maximum, 27
      fold) and induction of cytopathic effect (maximum, 3.8-fold) of dl520 were
      further augmented significantly. These results support the hypothesis that the
      enhanced oncolytic effect of dl520, after incubation with chemotherapeutic
      agents, is mediated by an increased accumulation of YB-1 in the nucleus (due to
      irinotecan) and by upregulation of CAR (due to trichostatin A). Thus, therapy
      combining virotherapy, chemotherapy, and histone deacetylase inhibitor treatment
      is a novel approach to enhance the oncolytic efficacy of dl520.

PMID- 16409126
TI  - Systemic correction of a fatty acid oxidation defect by intramuscular injection
      of a recombinant adeno-associated virus vector.
AB  - Mitochondrial beta-oxidation of fatty acids is required to meet physiologic
      energy requirements during illness and periods of fasting or physiologic stress,
      and is most active in liver and striated muscle. Acyl-CoA dehydrogenases of
      varying chain-length specificities represent the first step in the mitochondria
      for each round of beta-oxidation, each of which removes two-carbon units as
      acetyl-CoA for entry into the tricarboxylic acid cycle. We have used recombinant
      adeno-associated virus (rAAV) vectors expressing short-chain acyl-CoA
      dehydrogenase (SCAD) to correct the accumulation of fatty acyl-CoA intermediates
      in deficient cell lines. The rAAV-SCAD vector was then packaged into either rAAV
      serotype 1 or 2 capsids and injected intramuscularly into SCAD-deficient mice. A
      systemic effect was observed as judged by restoration of circulating butyryl-
      carnitine levels to normal. Total lipid content at the injection site was also
      decreased as demonstrated by noninvasive magnetic resonance spectroscopy (MRS).
      SCAD enzyme activity in the injected muscle was found at necropsy to be above the
      normal control mouse level. This study is the first to demonstrate the systemic
      correction of a fatty acid oxidation disorder with rAAV and the utility of MRS as
      a noninvasive method to monitor SCAD correction after in vivo gene therapy.

PMID- 16409127
TI  - DNA and adenoviral vectors encoding carcinoembryonic antigen fused to
      immunoenhancing sequences augment antigen-specific immune response and confer
      tumor protection.
AB  - A panel of vectors was constructed to encode carcinoembryonic antigen (CEA) fused
      at its C-terminal end to various polypeptides, so as to compare their
      immunogenicity by plasmid DNA immunization and adenovirus injection in wild-type
      and CEA transgenic (CEA.tg) mice. Fusions between CEA and the minimized domain of
      tetanus toxin fragment C (CEA-DOM) or the Fc portion of IgG1 (CEA-FcIgG) were
      identified as highly immunogenic and elicited significant CEA-specific antibody
      and CD8+ T cell responses. CEA.tg mice were protected from tumor growth on
      challenge with MC38-CEA tumor cells only when immunized with repeated injections
      of plasmid pV1J/CEA-DOM followed by Ad/CEA-DOM. Depletion of T-regulatory cells
      resulted in an increased immune response and antitumor effect with DNA plus
      adenovirus immunization. In addition, this protective effect was abrogated if the
      NK, CD4+, or CD8+ cell population from immunized mice was depleted before tumor
      challenge. Passive transfer studies demonstrated that CD4+ and CD8+ T cells and
      antibodies contributed to the antitumor effect, thus suggesting that a genetic
      vaccine based on the use of plasmid DNA and adenoviral vectors encoding CEA fused
      to immunoenhancing sequences augments CEA-specific immune responses and
      effectively protects from tumor development.

PMID- 16409128
TI  - Cloning of replication-incompetent herpes simplex viruses as bacterial artificial
      chromosomes to facilitate development of vectors for gene delivery into
      differentiated neurons.
AB  - We have previously described the adaptation of a tetracycline-regulated system of
      gene expression for herpes simplex virus (HSV) vectors and demonstrated that such
      a system was capable of inducible foreign gene expression in irreversibly
      differentiated neurons. These studies suggested that such gene delivery vectors
      would be especially useful for studying the neuron in vitro. Here, we describe
      the cloning of a replication-incompetent HSV vector as a bacterial artificial
      chromosome (BAC) to facilitate vector construction. Using prokaryotic genetic
      techniques for allele replacement, we demonstrate the ease of manipulation of the
      BAC-containing vector, including the construction of vector mutations for which
      there is no simple phenotypic selection. Such constructions include the insertion
      of a tetracycline-regulated gene cassette into the UL41 gene for regulated gene
      expression and the mutation of the UL48 gene to reduce vector toxicity. In
      addition, HSV vectors cloned as BACs can be sequentially modified to make
      multiple changes to the vector platform. Finally, using the BAC system, we
      constructed an HSV vector that expressed an inducible human superoxide dismutase
      1 (SOD1) gene for delivery into differentiated human NT-neurons (cells of the
      human embryonal carcinoma cell line NT2, which differentiate irreversibly into
      postmitotic neuron-like cells after treatment with retinoic acid). The results
      indicated that there is appreciable expression of SOD1 from this HSV vector in
      the presence of doxycycline and that vector-expressed SOD1 interacts with
      endogenous SOD1. Thus, the BAC system provides a practicable platform for
      construction and manipulation of HSV vectors that are suitable for gene delivery
      into postmitotic neurons in vitro.

PMID- 16409129
TI  - Suppression of the malignant phenotype in pancreatic cancer by overexpression of
      phospholipid hydroperoxide glutathione peroxidase.
AB  - Phospholipid glutathione peroxidase (PhGPx) reduces lipid hydroperoxides
      generated in biomembranes and also uses a wide range of reducing cofactors in
      addition to glutathione. PhGPx is synthesized as a mitochondrial PhGPx form (L
      form) and as a nonmitochondrial PhGPx form (S-form). Our aims were to determine
      whether overexpression of PhGPx altered pancreatic tumor cell behavior.
      Pancreatic cancer cell lines were found by Western blotting to have diminished
      levels of PhGPx-immunoreactive protein compared with normal human pancreas. To
      normalize the levels of this protein, PhGPx was overexpressed in MIA PaCa-2 and
      AsPC-1 human pancreatic cancer cells by infection with an adenovirus-PhGPx L-form
      construct (AdPhGPx- L-form) (0-200 MOI) or with an adenovirus-PhGPx S-form
      construct (AdPhGPx-S-form) (0-200 MOI), and cell growth, plating efficiency, and
      growth in soft agar were determined. Pancreatic cancer cells were also injected
      subcutaneously into nude mice and tumor volume was calculated. Single direct
      injections of the adenoviral- PhGPx constructs were made into preestablished
      tumors. In vitro, AdPhGPx-S-form demonstrated 80% tumor growth inhibition,
      whereas AdPhGPx-L-form demonstrated 95% tumor growth inhibition. Ad- PhGPx-L-form
      or AdPhGPx-S-form also decreased plating efficiency and growth in soft agar.
      AdPhGPx-Lform decreased in vivo tumor growth to a greater extent than did AdPhGPx
      S-form. Because of the growthinhibitory effects of PhGPx, lipid hydroperoxides
      may play an important role in the growth of pancreatic cancer.

PMID- 16409130
TI  - Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery.
AB  - The potential of short interfering RNA (siRNA) to be developed for therapeutic
      use against cancer depends on the availability of an efficient tumor-specific
      delivery vehicle. We have previously shown that a nanoscale nonviral liposome
      based complex that includes an anti-transferrin receptor single-chain antibody
      fragment as the targeting moiety can, when systemically administered,
      specifically and efficiently target primary and metastatic tumors and deliver
      molecules useful in gene medicine, including plasmid DNA and antisense
      oligonucleotides. Here we explore the ability of this complex to deliver a
      fluorescein-labeled siRNA to tumor cells in vivo and examine the intracellular
      localization in vitro by confocal microscopy. We show that the immunoliposome-
      siRNA complex maintains its nanoscale size and, using three separate tumor
      models, can efficiently and specifically deliver siRNA to both primary and
      metastatic disease after systemic delivery, thus increasing the possibility for
      translating the potent effects of siRNA observed in vitro into clinically useful
      therapeutics.

PMID- 16409131
TI  - Bioluminescence imaging of systemic tumor targeting using a prostate-specific
      lentiviral vector.
AB  - Developments in vector design using tissue-specific and tumor-specific promoters
      have led to significant improvements in tumor-targeting strategies. These
      developments combined with the ability to monitor gene expression by molecular
      imaging have facilitated the detection and prolonged monitoring of disease
      progression in small-animal models. Bioluminescence imaging offers a convenient
      and sensitive platform for monitoring gene expression patterns in preclinical
      models of gene therapy. Targeting a specific subset of cells/tissues via systemic
      delivery of vectors would be highly beneficial in gene therapy protocols. Using a
      two-step transcriptional amplification (TSTA)-based lentiviral vector (LV-TSTA),
      we demonstrate specific targeting of prostate tumors in vivo after systemic
      administration of lentivirus. Four days after intravenous administration of LV
      TSTA into adult severe combined immunodeficient (SCID) mice (n=5) carrying
      subcutaneous prostate tumors, we found significant levels of transduction at the
      tumor site when compared with other organs (p<0.05). Gene expression was
      sustained in the tumor for up to 3 weeks (7.3x10(4)+/-2x10(4) photons/
      sec/cm2/steradian (p/sec/cm2/sr) on day 4 and 7.0x10(4)+/-4x10(4) p/sec/cm2/sr on
      day 21). Low levels of transduction were also observed in the spleen and liver
      (5.0x10(2)+/-1.7x10(2) p/sec/cm2/sr). The results from this study support the use
      of TSTA-based lentiviral vectors for prostate tumor targeting after systemic
      delivery. Noninvasive imaging using such vectors should be useful for monitoring
      long-term gene expression in gene therapy applications.

PMID- 16409133
TI  - Angiogenesis.
AB  - Angiogenesis inhibitors for the treatment of cancer have now been approved by the
      Food and Drug Administration in the United States, and in 28 other countries
      including China. Clinical application of this new class of drugs is informed by
      certain principles from angiogenesis research. Oncogenic mutations initiate
      tumorigenesis, but angiogenesis is necessary for expansion of tumor mass. Two
      angiogenesis inhibitors have been developed that have a broad spectrum of
      anticancer activity, yet virtually no side effects. Endogenous angiogenesis
      inhibitors act as tumor suppressor proteins. The angiogenic response in vivo is
      based on the genetic background of the host. Several types of angiogenesis
      inhibitors reveal a biphasic, U-shaped curve of efficacy. "Antiangiogenic
      chemotherapy" is a novel approach to the treatment of drug resistance.

PMID- 16409134
TI  - Advances in radiation oncology.
AB  - Advances in radiation oncology have been made on three major fronts: biology,
      physics, and clinical application. Our biological understanding of how radiation
      kills cells and how malignant cells avoid damage has identified new targets for
      therapeutic manipulation. Research in physics has yielded sophisticated methods
      to direct the deposition of radiation energy in ways that enhance target coverage
      while minimizing dose to normal structures as much as possible. Intensity
      modulated radiation therapy (IMRT) and image-guided radiation therapy represent
      new paradigms in treatment planning and dose delivery. Clinical management of the
      cancer patient is multidisciplinary. Increasingly, combinations of radiation and
      chemotherapy, with or without surgery, are enhancing cure rates, often with
      preservation of organ function. Taken together, these advances have increased the
      effectiveness of radiation therapy and promise better treatment results in the
      future.

PMID- 16409135
TI  - Bortezomib: proteasome inhibition as an effective anticancer therapy.
AB  - VELCADER (bortezomib, Millennium Pharmaceuticals, Inc., Cambridge, MA, and
      Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ) is
      a first-in-class proteasome inhibitor developed specifically for use as an
      antineoplastic agent. Inhibition of the proteasome results in disruption of
      homeostatic mechanisms within the cell that can lead to cell death. Bortezomib's
      first indication, for the treatment of relapsed myeloma in patients who have
      received at least two prior treatments and progressed on their previous
      treatment, was based in part on the magnitude of activity demonstrated in phase
      II trials. Bortezomib is currently indicated for patients who have received at
      least one prior therapy in the United States and European Union, although
      patients in the European Union must have already undergone bone marrow
      transplantation or be unsuitable for the procedure. A phase III trial
      demonstrated the superiority of bortezomib over high-dose dexamethasone in
      response rate, time to progression, and survival in patients with myeloma who had
      relapsed after 1-3 prior therapies. Clinical development is ongoing to
      investigate its activity as monotherapy and in combination regimens for the
      treatment of non-Hodgkin's lymphoma, solid tumors, and earlier presentations of
      myeloma.

PMID- 16409136
TI  - Chemoprevention of prostate cancer.
AB  - Prostate cancer is an attractive target for chemoprevention because of its
      ubiquity, treatment-related morbidity, long latency between premalignant lesions
      and clinically evident cancer, and defined molecular pathogenesis. The Prostate
      Cancer Prevention Trial has provided the first firm evidence that this cancer can
      be prevented by a relatively nontoxic oral agent. Additional agents, many of
      which are antioxidants with antiandrogenic effects, are being tested (or soon
      will be) in large clinical trials. The current body of evidence is insufficient
      to make a routine recommendation of any dietary or nutritional supplement for the
      prevention of prostate cancer.

PMID- 16409137
TI  - Effective cancer therapy through immunomodulation.
AB  - MAbs directed toward tumor cells, tumor neovasculature, and host negative
      immunoregulatory elements (checkpoints) have emerged as useful immunotherapeutic
      agents against cancer. However, effective active modulation of the immune
      response with anticancer vaccines will require identifying appropriate tumor
      rejection antigens; optimizing the interactions of peptides, antigen-presenting
      cells, and T cells; and blockading negative immunological checkpoints that impede
      an effective immune response. Checkpoints being targeted include CTLA-4 and PD1
      that are negative signaling receptors expressed on activated T cells, CD4+CD25+
      Foxp3-expressing Tregs (suppressor T cells), IL-2-mediated activation-induced
      cell death (AICD), and the cytokine TGFbeta.

PMID- 16409138
TI  - Molecular approaches in pediatric oncology.
AB  - The use of molecular approaches has become part of the standard of care in the
      management of pediatric cancer patients. Molecular approaches are now included in
      the initial diagnosis, definition of prognostically distinct patient subgroups,
      selection of patients for specific therapies, prediction of risk for toxicities
      to therapy, and monitoring of patients receiving both conventional and novel
      targeted therapies. This clinical application of molecular medicine has been
      based on a growing molecular understanding of cancer biology. Studies of
      pediatric cancers have contributed to this understanding in many ways. We present
      a model for understanding cancer biology, using specific examples taken from
      pediatric oncology, and then discuss the application of molecular techniques to
      the clinical management of pediatric cancer patients.

PMID- 16409139
TI  - Molecular imaging in the development of cancer therapeutics.
AB  - Researchers have made great progress in defining genetic and molecular
      alterations that contribute to cancer. New therapeutic targets have been
      identified and targeted therapeutic agents have been developed, but our ability
      to evaluate potential drugs has not kept pace. Molecular imaging technologies
      that monitor biological processes and/or measure levels of targeted
      macromolecules can contribute significantly to preclinical and clinical drug
      evaluation. This article describes the drug discovery process, economic problems
      facing drug discovery and development, and successes and failures in this realm.
      We briefly describe the available molecular imaging tools, with emphasis on
      positron emission tomography. We discuss biological processes that are altered in
      tumors and can be measured by molecular imaging; examples include gene
      expression, signal transduction, tumor cell metabolism, proliferation, apoptosis,
      hypoxia, and angiogenesis. We conclude with a proposal to integrate molecular
      imaging into the drug development process.

PMID- 16409140
TI  - Pharmacogenomics and individualized drug therapy.
AB  - Pharmacogenetics deals with inherited differences in the response to drugs. The
      best-recognized examples are genetic polymorphisms of drug-metabolizing enzymes,
      which affect about 30% of all drugs. Loss of function of thiopurine S
      methyltransferase (TPMT) results in severe and life-threatening hematopoietic
      toxicity if patients receive standard doses of mercaptopurine and azathioprine.
      Gene duplication of cytochrome P4502D6 (CYP2D6), which metabolizes many
      antidepressants, has been identified as a mechanism of poor response in the
      treatment of depression. There is also a growing list of genetic polymorphisms in
      drug targets that have been shown to influence drug response. A major limitation
      that has heretofore moderated the use of pharmacogenetic testing in the clinical
      setting is the lack of prospective clinical trials demonstrating that such
      testing can improve the benefit/risk ratio of drug therapy.

PMID- 16409141
TI  - Avian flu to human influenza.
AB  - Influenza A viral infection causes substantial annual morbidity and mortality
      worldwide, particularly for infants, the elderly, and the immunocompromised. The
      virus mainly replicates in the respiratory tract and is spread by respiratory
      secretions. A growing concern is the recent identification of H5N1 strains of
      avian influenza A in Asia that were previously thought to infect only wild birds
      and poultry, but have now infected humans, cats, pigs, and other mammals, often
      with fatal results, in an ongoing outbreak. A human pandemic with H5N1 virus
      could potentially be catastrophic because most human populations have negligible
      antibody-mediated immunity to the H5 surface protein and this viral subtype is
      highly virulent. Whether an H5N1 influenza pandemic will occur is likely to hinge
      on whether the viral strains involved in the current outbreak acquire additional
      mutations that facilitate efficient human-to-human transfer of infection.
      Although there is no historical precedent for an H5N1 avian strain causing
      widespread human-to-human transmission, some type of influenza A pandemic is very
      likely in the near future. The possibility of an H5N1 influenza pandemic has
      highlighted the many current limitations of treatment with antiviral agents and
      of vaccine production and immunogenicity. Future vaccine strategies that may
      include more robust induction of T-cell responses, such as cytotoxic T
      lymphocytes, may provide better protection than is offered by current vaccines,
      which rely solely or mainly on antibody neutralization of infection.

PMID- 16409142
TI  - Emerging therapeutics for chronic hepatitis B.
AB  - Hepatitis B is a global health problem. Patients with chronic hepatitis B (CHB)
      carry a significant risk to eventually develop cirrhotic liver disease. Recent
      therapeutic advances against CHB offer excellent potential for long-term
      suppression of hepatitis B virus (HBV) replication during antiviral therapy, and
      occasionally a durable remission off medication. Selection of appropriate
      patients for antiviral therapy depends on identification of HBV replication and
      an elevated alanine aminotransferase level or histologic liver injury. Pegylated
      interferon alpha offers potent immunomodulatory and antiviral activity with the
      potential for durability, but also with adverse effects and significant cost. The
      nucleoside or nucleotide analogs, lamivudine, adefovir, and entecavir, suppress
      HBV replication and are extremely well-tolerated, but long-term or even lifelong
      therapy is required. Most experience has been gained with lamivudine, but viral
      resistance occurs frequently. Newer analogs appear to be relatively free of this
      problem. Approaches using a combination of agents have promise, but have yet to
      be proven superior to individual drugs alone.

PMID- 16409143
TI  - The rotavirus vaccine saga.
AB  - Rotavirus is the single most common cause of acute, dehydrating gastroenteritis
      worldwide. This is a highly contagious and highly democratic disease. The attack
      rate in infants and young children is similar regardless of sanitation,
      socioeconomics or geography. Rotavirus vaccine development began in the early
      1980s using a "Jennerian" approach based on rotaviruses that normally infect
      animals. Although these vaccines were found to be generally safe, protection from
      disease was inconsistent. The second generation of vaccines was based on the same
      animal viruses configured to carry the relevant coat proteins of human
      rotaviruses. An attenuated human rotavirus vaccine has also been developed. After
      close to 20 years of laboratory and clinical studies, safe and effective
      rotavirus vaccines are approaching regulatory approval.

PMID- 16409144
TI  - West Nile virus: epidemiology and clinical features of an emerging epidemic in
      the United States.
AB  - West Nile virus (WNV) was first detected in North America in 1999 during an
      outbreak of encephalitis in New York City. Since then the virus has spread across
      North America and into Canada, Latin America, and the Caribbean. The largest
      epidemics of neuroinvasive WNV disease ever reported occurred in the United
      States in 2002 and 2003. This paper reviews new information on the epidemiology
      and clinical aspects of WNV disease derived from greatly expanded surveillance
      and research on WNV during the past six years.

PMID- 16409145
TI  - Prostatitis/chronic pelvic pain syndrome.
AB  - We review the diagnosis, categorization, and treatment of prostatitis/chronic
      pelvic pain syndrome based on the National Institutes of Health (NIH)
      classification. Prostatitis is an extremely common syndrome that afflicts 2%-10%
      of men. Formerly a purely clinical diagnosis, prostatitis is now classified
      within a complex series of syndromes (NIH category I-IV prostatitis) that vary
      widely in clinical presentation and response to treatment. Acute bacterial
      prostatitis (category I) and chronic bacterial prostatitis (category II) are
      characterized by uropathogenic infections of the prostate gland that respond well
      to antimicrobial treatment. In contrast, chronic prostatitis/chronic pelvic pain
      syndrome (category III), which accounts for 90%-95% of prostatitis cases, is of
      unknown etiology and is marked by a mixture of pain, urinary, and ejaculatory
      symptoms with no uniformly effective therapy. Asymptomatic inflammatory
      prostatitis (category IV) is an incidental finding of unknown clinical
      significance. This review describes the current status of prostatitis syndromes
      and explores the future prospects of new diagnostic tools and therapies.

PMID- 16409146
TI  - Celiac disease.
AB  - Celiac disease is an autoimmune disease that occurs in genetically predisposed
      individuals as the result of an immune response to gluten. This immune response
      occurs in both the lamina propria and the epithelium of the small intestine.
      There is a close link to HLA DQ2 and DQ8, although these HLA genes account for
      only 40% of the genetic influence. Environmental factors, such as the amount and
      timing of gluten administration in infancy, as well as breastfeeding, influence
      the disease. Serologic screening studies that use sensitive and specific antibody
      tests have revealed the disease to be common, occurring in approximately 1% of
      the population. Clinical presentations are diverse and atypical; the majority of
      patients lack diarrhea. Therapy is a gluten-free diet that requires avoidance of
      wheat, rye, and barley, although there is potential for other therapies based on
      our understanding of the pathophysiology of the disease.

PMID- 16409147
TI  - Amyloidosis.
AB  - Amyloidosis is a clinical disorder caused by extracellular deposition of
      insoluble abnormal fibrils, derived from aggregation of misfolded, normally
      soluble, protein. About 23 different unrelated proteins are known to form amyloid
      fibrils in vivo, which share a pathognomonic structure although they are
      associated with clinically distinct conditions. Systemic amyloidosis, with
      amyloid deposits in the viscera, blood vessel walls, and connective tissue, is
      usually fatal and is the cause of about one per thousand deaths in developed
      countries. This rarity and the variable involvement of different organs and
      tissues are often responsible for missed or delayed diagnosis, and amyloidosis
      remains a considerable clinical challenge. However, recent elucidation of
      important aspects of pathogenesis, as well as developments in diagnosis,
      monitoring, and treatment, have greatly improved outcomes, especially when
      patients are managed in specialist centers.

PMID- 16409148
TI  - Surgical treatment of morbid obesity.
AB  - Obesity is a major epidemic in developed countries. It induces or exacerbates
      hypertension, diabetes mellitus, obstructive sleep apnea, dyslipidemia, and many
      other disease processes, which cumulatively contribute to premature mortality on
      a scale rivaling that of smoking. At present, bariatric surgery is the only
      therapeutic modality that can produce sustained weight loss and halt or resolve
      comorbidities. This success results from the ability to perform the operation
      reliably, usually laparoscopically, with low mortality. The most commonly
      performed operation is Roux-en-Y gastric bypass. Other bypasses discussed in this
      review include biliopancreatic diversion with and without duodenal switch. Purely
      restrictive operations, especially adjustable gastric banding, have a lower risk
      but are somewhat less effective. We focus on the more controversial aspects of
      commonly accepted operations, including patient selection, the spectrum and
      frequency of complications, and the long-term outcome.

PMID- 16409149
TI  - Therapeutic approaches to preserve islet mass in type 2 diabetes.
AB  - Type 2 diabetes is characterized by hyperglycemia resulting from insulin
      resistance in the setting of inadequate beta-cell compensation. Currently
      available therapeutic agents lower blood glucose through multiple mechanisms but
      do not directly reverse the decline in beta-cell mass. Glucagon-like peptide-1
      (GLP-1) receptor agonists, exemplified by Exenatide (exendin-4), not only acutely
      lower blood glucose but also engage signaling pathways in the islet beta-cell
      that lead to stimulation of beta-cell replication and inhibition of beta-cell
      apoptosis. Similarly, glucose-dependent insulinotropic polypeptide (GIP) receptor
      activation stimulates insulin secretion, enhances beta-cell proliferation, and
      reduces apoptosis. Moreover, potentiation of the endogenous postprandial levels
      of GLP-1 and GIP via inhibition of dipeptidyl peptidase-IV (DPP-IV) also expands
      beta-cell mass via related mechanisms. The thiazolidinediones (TZDs) enhance
      insulin sensitivity, reduce blood glucose levels, and also preserve beta-cell
      mass, although it remains unclear whether TZDs affect beta-cell mass via direct
      mechanisms. Complementary approaches to regeneration of beta-cell mass involve
      combinations of factors, exemplified by epidermal growth factor and gastrin,
      which promote islet neogenesis and ameliorate diabetes in rodent studies.
      Considerable preclinical data support the concept that one or more of these
      therapeutic approaches, alone or in combination, may potentially reverse the
      decline in beta-cell mass that is characteristic of the natural history of type 2
      diabetes.

PMID- 16409150
TI  - Enzyme replacement for lysosomal diseases.
AB  - Following the demonstration of the nature of the enzymatic defects in the
      sphingolipid storage disorders in the mid-1960s, consideration was directed to
      the development of therapy for patients with these conditions. High on the list
      of possibilities was enzyme supplementation or replacement. Many years of arduous
      investigation and the development of novel protein targeting strategies were
      required to bring this concept to fruition. Enzyme replacement therapy (ERT) was
      eventually shown to be extraordinarily effective for patients with Gaucher
      disease, the most prevalent metabolic storage disorder of humans. Demonstration
      of the benefit of ERT in this disorder led to the extension of this approach to
      the treatment of other lysosomal storage disorders. This review presents the
      current status and anticipated developments in this field.

PMID- 16409151
TI  - Genetic basis of lipodystrophies and management of metabolic complications.
AB  - Selective loss of body fat is the hallmark of patients with lipodystrophies.
      Among genetic lipodystrophies, fat loss is observed either from birth, as in
      congenital generalized lipodystrophy, or later in life, as in familial partial
      lipodystrophy. The extent of fat loss also varies among subtypes of
      lipodystrophies. Patients develop hyperinsulinemia, acanthosis nigricans,
      hypertriglyceridemia, diabetes mellitus, and hepatic steatosis. Defects in
      several genes, such as those encoding an enzyme (AGPAT2), a nuclear receptor
      (PPARgamma), a nuclear lamina protein (LMNA) and its processing endoprotease
      (ZMPSTE24), a kinase (AKT2), and a protein of unknown function (BSCL2), have been
      found in patients with genetic lipodystrophies. Additional loci remain to be
      discovered. We discuss features of autosomal recessive and dominant types of
      lipodystrophies and therapeutic interventions available for these patients.

PMID- 16409152
TI  - Nuclear receptors in lipid metabolism: targeting the heart of dyslipidemia.
AB  - Dyslipidemia is the sine qua non of atherosclerosis, but it is also strongly
      associated with the metabolic syndrome, obesity, diabetes, and fatty liver
      disease. The molecular basis for future therapies requires understanding the
      pivotal role of nuclear hormone receptors in lipid and inflammatory homeostasis.
      This review summarizes evidence that the liver X receptor (LXR) and peroxisome
      proliferator-activated receptor (PPAR) are key transcriptional regulators in
      lipid metabolism. Additionally, their effects on glucose homeostasis and
      inflammation make LXR and PPAR signaling networks attractive molecular targets
      for managing lipid-related diseases.

PMID- 16409154
TI  - Therapeutic use of calcimimetics.
AB  - It has long been recognized that the secretion of PTH by chief cells in the
      parathyroid gland is regulated by extracellular ionized calcium. The molecular
      mechanism by which extracellular Ca2+ performs this feat was deduced by the
      cloning of the extracellular calcium-sensing receptor (CaSR) in 1993 in the
      laboratories of Brown and Hebert. The CaSR is a G protein-coupled cell surface
      receptor that belongs to family 3 of the GPCR superfamily. The CaSR senses the
      extracellular ionic activity of the divalent minerals Ca2+ and Mg2+ and
      translates this information, via a complex array of cellular signaling pathways,
      to modify cell and tissue function. Genetic studies have demonstrated that the
      activity of this receptor determines the steady-state plasma calcium
      concentration in humans by regulating key elements in the calcium homeostatic
      system. CaSR agonists (calcimimetics) and antagonists (calcilytics) have been
      identified and have provided both current and potential therapies for a variety
      of disorders. Calcimimetics can effectively reduce PTH secretion in all forms of
      hyperparathyroidism. They are likely to become a major therapy for secondary
      hyperparathyroidism associated with renal failure and for treatment of certain
      patients with primary hyperparathyroidism. On the therapeutic horizon are
      calcilytics that can transiently increase PTH and may prove useful in the
      treatment of osteoporosis.

PMID- 16409153
TI  - Hemochromatosis: genetics and pathophysiology.
AB  - A number of genetic disorders can result in the accumulation of excess iron in
      the body. These causes of hereditary hemochromatosis include defects in genes
      encoding HFE, transferrin receptor 2, ferroportin, hepcidin, and hemojuvelin.
      Hepcidin, with its cognate receptor, ferroportin, has emerged as a central
      regulator of iron homeostasis; all of the known causes of hemochromatosis appear
      to prevent this system from functioning normally. The most common form of primary
      hemochromatosis is that caused by C282Y mutation of the HFE gene. This mutation
      is most prevalent among Northern Europeans. Although the frequency of the
      homozygous genotype is approximately 5 per 1000, the disease itself is quite rare
      because the clinical penetrance of the genotype is very low.

PMID- 16409155
TI  - Toward a unified theory of renal progression.
AB  - Various disciplines within nephrology investigate the mechanisms by which kidneys
      fail. Progress in the areas of glomerular hemodynamics, proteinuria, tubular
      biology, interstitial nephritis, fibroblast formation, and fibrosis have added
      kernels of information that together support a unified theory of renal
      progression. Prevention of progression to end-stage disease has largely focused
      on control of systemic and glomerular hypertension. Current success in delaying a
      decline in glomerular filtration rate underlines the promise of a more
      comprehensive approach. New knowledge about the cell biology of progression also
      suggests that other adjunctive therapies may be possible. We describe the
      progress and highlight those spheres where new-targeted interventions may arise.

PMID- 16409156
TI  - Cd4+Cd25+ regulatory T cells and their therapeutic potential.
AB  - The human immune system mounts specific responses to a vast array of antigens.
      Although this is clearly beneficial in fighting off harmful infections and
      cancerous cells, the system must be carefully controlled to ensure that normal
      self-antigens are not targeted. A recently characterized subset of T cells,
      identified by their cell surface expression of CD4 and CD25, is critical in
      regulating the function of other immune cells and preventing potentially harmful
      autoimmune responses. This article reviews what is currently known about these so
      called regulatory T cells and discusses the therapeutic potential of these cells
      to modulate human immune-based diseases.

PMID- 16409157
TI  - Umbilical cord blood transplantation and banking.
AB  - Umbilical cord blood transplantation (UCBT) is an expanding practice for both
      pediatric and adult patients. Rapid availability, low risk of infectious disease
      transmission, lower risk of graft-versus-host disease, and lack of risk for the
      donor makes UCB an attractive alternative source of hematopoietic stem cells for
      transplantation. We review the state of the art of pediatric and adult UCBT and
      important aspects of UCB banking. Current strategies to improve clinical results
      and expand access to UCBT to a larger number of adult patients are discussed. New
      approaches to enhance hematopoietic recovery by the use of accessory cells or
      direct intra-bone marrow injection are also reviewed.

PMID- 16409159
TI  - Use of stents to treat extracranial cerebrovascular disease.
AB  - Stent-assisted carotid angioplasty (CAS) is increasingly utilized for
      hemodynamically significant stenoses of the extracranial carotid artery. Carotid
      endarterectomy (CEA) is still considered the gold standard in the management of
      symptomatic hemodynamically significant carotid stenoses. However, endovascular
      device technology is rapidly evolving and the recent introduction of embolic
      filtration devices (EFD) proved to reduce periprocedural stroke rates in CAS
      considerably. Several randomized multicenter trials are currently recruiting
      patients to compare CAS with EFD to carotid endarterectomy in different cohorts,
      such as patients at high surgical risk for CEA and those with asymptomatic
      stenosis. The review presents current developments in CAS.

PMID- 16409160
TI  - New directions in cardiac transplantation.
AB  - More than three decades of clinical experience in cardiac transplantation
      resulted in the spread of the procedure worldwide with a wealth of knowledge and
      advancements. Developments included liberalization of recipient and donor
      selection criteria, improved surgical techniques, novel immunosuppressive drugs
      and protocols, new rejection surveillance techniques, and better understanding of
      the pathophysiology of cardiac allograft vasculopathy to direct interventions for
      prevention and treatment.

PMID- 16409158
TI  - Current concepts in thrombotic thrombocytopenic purpura.
AB  - Recent advances have demonstrated that thrombotic thrombocytopenic purpura (TTP),
      characterized by widespread thrombosis in the arterioles and capillaries, is
      caused by deficiency of a circulating zinc metalloprotease, ADAMTS13. Two types
      of TTP are recognized: autoimmune TTP, caused by inhibitory antibodies of
      ADAMTS13, and hereditary TTP, caused by genetic mutations of ADAMTS13. This
      article reviews the characteristics and function of ADAMTS13, the mechanism by
      which ADAMTS13 deficiency may lead to thrombosis, and the causes of ADAMTS13
      deficiency. It also discusses how the new knowledge may improve the diagnosis and
      treatment of this previously mysterious disorder.

PMID- 16409161
TI  - Exercise-induced ventricular arrhythmias in patients with no structural cardiac
      disease.
AB  - We review the clinical and genetic disorders associated with exercise-induced
      ventricular arrhythmias in patients with normal hearts. Foremost are those with
      catecholaminergic polymorphic ventricular tachycardia due to abnormalities in
      either the ryanodine receptor 2 genes (RyR2) or the calsequestrin genes (CASQ).
      These patients manifest ventricular premature beats and polymorphic ventricular
      tachycardia in response to exercise or on exposure to catecholamines. A great
      deal of basic information has been accumulated suggesting that these arrhythmias
      are caused by abnormalities in Ca2+ metabolism. The ensuing cytosolic Ca2+
      overload results in delayed after-depolarizations and extrasystolic Ca2+ waves,
      leading to polymorphic ventricular tachycardia. Most of these patients will
      respond to beta-blocker therapy but a significant minority (30%) will require a
      defibrillator. Advances in genetic testing allow better understanding of this
      syndrome.

PMID- 16409162
TI  - Cardiotoxicity induced by chemotherapy and antibody therapy.
AB  - Modern cancer therapy employs a combination of chemotherapy, antibody-based
      therapy, radiotherapy, and surgery to prolong life and provide cure. However,
      many of the chemotherapy agents and antibodies, either singly or in combination,
      can affect the cardiovascular system. Common cardiovascular manifestations of
      these therapies include heart failure, ischemia, hypotension, hypertension,
      edema, QT prolongation, bradyarrhythmia, and thromboembolism. The patient's age,
      underlying cardiovascular status, and genetic background, as well as the route of
      drug administration and dosage, can all contribute to the development of
      cardiotoxicity. Strategies to monitor for and to manage these effects are
      discussed in this review.

PMID- 16409163
TI  - "Sundowning" and other temporally associated agitation states in dementia
      patients.
AB  - The behavioral and neuropsychiatric symptoms of dementia and Alzheimer's disease
      have become an increasingly important focus of clinical research. These symptoms
      also pose a tremendous challenge to families and caregivers. The late
      afternoon/evening exacerbation of behavioral symptoms in dementia has been
      recognized by clinicians for >60 years. Researchers have utilized a variety of
      increasingly sophisticated tools to examine the circadian, hormonal,
      physiological, and epidemiological correlations with sundowning behavior.
      Although treatment remains largely empirical, an improved understanding of the
      complex relationships that drive sundowning behavior should lead to more
      effective therapies in the future.

PMID- 16409164
TI  - Current pharmacotherapy for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects
      approximately 4.5 million people in the United States. The mainstays of current
      pharmacotherapy for AD are compounds aimed at increasing the levels of
      acetylcholine in the brain, thereby facilitating cholinergic neurotransmission
      through inhibition of the cholinesterases. These drugs, known as
      acetylcholinesterase inhibitors (AChEIs), were first approved by the U.S. Food
      and Drug Administration (FDA) in 1995 based on clinical trials showing modest
      symptomatic benefit on cognitive, behavioral, and global measures. In 2004 the
      FDA approved memantine, an NMDA antagonist, for treating dementia symptoms in
      moderate to severe AD cases. In clinical practice, memantine may be co
      administered with an AChEI, although neither drug individually or in combination
      affects the underlying pathophysiology of dementia. Dementia in AD results from
      progressive synaptic loss and neuronal death. As knowledge of the mechanisms
      responsible for neurodegeneration in AD increases, it is anticipated that
      neuroprotective drugs to slow or prevent neuronal dysfunction and death will be
      developed to complement current symptomatic treatments.

PMID- 16409165
TI  - New treatments for neuropathic pain.
AB  - Existing treatments for neuropathic pain deliver inadequate pain relief,
      unacceptable side effects, or both. The unmet medical need for more effective
      treatment is driving a large volume of research to discover new drugs. Most
      existing treatments are drugs introduced to treat other pain conditions or other
      medical conditions, such as antidepressants and anticonvulsants, which were found
      empirically to be effective for neuropathic pain. Only recently have drug
      discovery efforts have become mechanistically driven, addressing targets
      identified by a molecular neurobiological approach to the pathophysiology of
      neuropathic states.

PMID- 16409166
TI  - Plant, synthetic, and endogenous cannabinoids in medicine.
AB  - Although used for more than 4000 years for recreational and medicinal purposes,
      Cannabis and its best-known pharmacologically active constituents, the
      cannabinoids, became a protagonist in medical research only recently. This
      revival of interest is explained by the finding in the 1990s of the mechanism of
      action of the main psychotropic cannabinoid, Delta9-tetrahydrocannabinol (THC),
      which acts through specific membrane receptors, the cannabinoid receptors. The
      molecular characterization of these receptors allowed the development of
      synthetic molecules with cannabinoid and noncannabinoid structure and with higher
      selectivity, metabolic stability, and efficacy than THC, as well as the
      development of antagonists that have already found pharmaceutical application.
      The finding of endogenous agonists at these receptors, the endocannabinoids,
      opened new therapeutic possibilities through the modulation of the activity of
      cannabinoid receptors by targeting the biochemical mechanisms controlling
      endocannabinoid tissue levels.

PMID- 16409167
TI  - The Health Insurance Portability and Accountability Act of 1996 (HIPAA) privacy
      rule: implications for clinical research.
AB  - In the short time since it became effective for health care organizations, a
      privacy regulation issued under the Health Insurance Portability and
      Accountability Act of 1996 (HIPAA) has had a significant adverse impact on the
      conduct of clinical research in the United States, without a substantial
      corresponding increase in privacy protection for research participants. Some of
      the problems associated with HIPAA have been resolved through revisions since the
      regulation's initial promulgation in December 2000, and other problems can be
      addressed by better educating health care providers and researchers about its
      requirements and available alternatives for compliance; however, considerable
      structural challenges remain. These constitute substantial barriers to research
      and resulting medical advances. Additional revisions to HIPAA based on the
      principles and trade-offs reflected in the Common Rule-which responsibly balances
      an individual's interest in privacy protection with the public interest in
      gaining knowledge through biomedical research-can go a long way to remedying
      remaining flaws in the system.

PMID- 16409168
TI  - Continuous hybridoma bioreactor: sensitivity analysis and optimal control.
AB  - Animal cell culture has already established itself as a mature technology able to
      make a wide range of valuable products, the actual focus being to find the
      competitive bioreactor design and operating conditions for increasing production.
      A complex analysis, implying sensitivity calculus and optimal control
      computation, is done for a system composed of a continuous perfectly mixed
      bioreactor, with cell recirculation, a cell separator, a mixer and a purge. The
      bioreactor's sensitivity to the control parameters is measured by a new concept,
      entropic density, developed from the notion of Shannon entropy. An optimization
      procedure based on a genetic-algorithms approach is applied for the computation
      of the inlet flow profile in time, which guarantees optimum monoclonal-antibody
      production. Our studies, including the present one, proved that the best approach
      to obtain high production is to use a hybrid operating sequence: fed-batch mode
      followed by the continuous mode.

PMID- 16409169
TI  - Canadian multi-institutional survey of immune tolerance therapy (ITT) --
      experience with the use of recombinant factor VIII for ITT.
AB  - Immune tolerance therapy (ITT) is currently the most effective approach to
      eradicate inhibitors in patients with haemophilia A. Limited evidence suggests
      that the use of plasma-derived factor VIII (pdFVIII) for ITT may be associated
      with a greater success rate than recombinant factor VIII (rFVIII). Analysis of
      ITT cases in Canada offered the opportunity to examine the success rate of using
      rFVIII for ITT, as rFVIII has been used almost exclusively for Canadian
      haemophilia A patients since 1994. The results of 32 patients from five
      haemophilia treatment centres were collated. Three patients continue on ITT. Of
      the 29 patients who completed ITT, 25 (86.2%) used rFVIII exclusively, and four
      used pdFVIII exclusively or pdFVIII followed by rFVIII. The initial FVIII dosing
      frequency was once per day in 72.4% of patients at an average dose of 98 U kg(-1)
      (range 50-200). Eight patients (25%) received one or more adjuvant therapies. The
      median duration of ITT was 1.1 years (mean 1.5 years, range 9 days to 6 years).
      The overall success rate of the 29 patients who completed ITT was 79.3% (23/29),
      which is comparable with the results of immune tolerance registries. Our results
      suggest that the success rate of ITT using rFVIII is not inferior to the results
      with pdFVIII.

PMID- 16409170
TI  - Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience.
AB  - When a high titre inhibitor develops in a patient with haemophilia, attempts are
      made to eradicate it through immune tolerance induction therapy (ITI) involving
      the frequent and regular administration of factor, usually for months to years.
      ITI is successful in only two thirds of patients prompting investigators to
      explore alternate regimens to use in haemophiliacs failing conventional ITI.
      Rituximab is an anti-CD20 monoclonal antibody, which has shown promise in the
      treatment of B-cell-mediated disorders. We developed a protocol for the use of
      rituximab in haemophilia A (HA) patients failing conventional ITI or in those
      haemophiliacs where the likelihood of success of conventional ITI is poor.
      Patients receive 375 mg m(-2) of intravenous rituximab weekly for 4 weeks
      followed by monthly (up to 5 months) until inhibitor disappearance and
      establishment of normal FVIII pharmacokinetics (recovery and half-life). Patients
      are concurrently placed on recombinant FVIII (100 U kg(-1) day(-1)). We have
      placed five haemophiliacs (four children with severe HA, and one adult with mild
      HA) on this protocol. In three patients (two with severe HA and one with mild HA)
      inhibitors disappeared although in neither severe haemophiliac did FVIII
      pharmacokinetics completely normalize. The fourth patient had a significant drop
      in inhibitor titres although not a complete disappearance of the inhibitor. All
      four of these patients ceased bleeding following rituximab. The fifth patient had
      no response to rituximab. This non-responding patient was not placed on
      concurrent FVIII. Our five cases suggest that rituximab may hold promise in the
      eradication of inhibitors. Prospective randomized studies are required to
      determine the value of this agent in inhibitor management.

PMID- 16409171
TI  - Congenital factor VII deficiency: therapy with recombinant activated factor VII -
      a critical appraisal.
AB  - Congenital factor VII (FVII) deficiency is a rare bleeding disorder with high
      phenotypic variability, and optimal management has yet to be determined.
      Treatment has traditionally involved FVII replacement therapy using fresh frozen
      plasma, prothrombin complex concentrates or plasma-derived FVII concentrates.
      Recombinant activated FVII (rFVIIa, NovoSeven(R)), the first recombinant
      treatment option, has recently been approved in the European Union for use in
      congenital FVII deficiency, but has been available on an emergency and
      compassionate use basis since 1988. In FVII deficiency, rFVIIa serves as
      substitution therapy as it provides the physiological ligand (FVIIa) for tissue
      factor, its receptor exposed at the site of vascular injury. This paper provides
      an overview of published and unpublished experience with rFVIIa in patients with
      congenital FVII deficiency from the NovoSeven compassionate and emergency use
      programmes (1988-99) and of independent reports in the literature. Recombinant
      FVIIa has been reported to provide effective haemostasis in patients of all ages
      and in a range of bleeding situations, including acute central nervous
      system/life-threatening bleeding episodes (15 episodes in 12 patients), non-life
      threatening bleeding episodes (>32 episodes in 17 patients), surgery (>40
      interventions in 25 patients) and childbirth (three women). Preliminary reports
      suggest that it may also be effective prophylactically. The risk of thrombosis in
      FVII-deficient patients treated with rFVIIa is unknown, as is the occurrence of
      inhibiting antibodies. A postlicensure pharmacovigilance registry (Seven
      Treatment Evaluation Registry) has been set up to continue to monitor the
      efficacy and safety (including alloantibody development) of rFVIIa in patients
      with FVII deficiency.

PMID- 16409172
TI  - Long-term evaluation of radioisotope synovectomy with Yttrium 90 for chronic
      synovitis in Turkish haemophiliacs: Izmir experience.
AB  - Since 2001 we have performed 105 radioisotope synovectomy (RS) in 65 children and
      young adults, age ranging from 3 to 25 years with a average of 15 years in Ege
      University Hospital, Izmir, Turkey. One fourth of cases were below 10 years of
      age. All patients had severe haemophilia A and B. Ten patients (17 joints) had
      high responder inhibitor. We prefer to use Yttrium 90 for all joints (5 mCi for
      knees; 2 mCi for others). The knees were injected in 56 cases, elbows in 24
      cases, ankles in 23 cases and shoulders in two cases. Steroid injections were not
      preferred as the principle drug of choice. Mean follow-up period after procedure
      was 2 years (range: 6 months to 3.5 years). All inhibitor patients had
      satisfactory results. The best results were obtained in elbows than knees and
      ankles. Excellent rates (no bleeding) were observed in grade-II synovitis 84% for
      knees, 93% for elbows and 50% for ankles. Because of the excellent and good
      response (bleeding reduction to 75%), rates were 100% for knees and elbows and
      92% for ankles. In six cases, repeated injections were given at 6-month interval
      and all of them had good results. The grading of synovitis seems to be an
      important parameter than the age of the patient. Even in patients below 10 years
      of age, outcomes are not satisfactory in all joints with grade-III vs. grade-II
      synovitis (12% vs. 73%). No serious complications were observed during and after
      procedure except two cases. A mild and transient inflammatory reaction was
      observed in the ankle. There was a minimal radioisotope leakage to superficial
      skin in the elbow. RS seems to be a safe and effective treatment for chronic
      synovitis causing recurrent joint bleedings.

PMID- 16409173
TI  - Measuring patients' perceptions on their functional abilities: validation of the
      Haemophilia Activities List.
AB  - Recently, the Haemophilia Activities List (HAL), a haemophilia-specific self
      assessment questionnaire to assess a patient's self-perceived functional ability,
      was introduced and a limited pilot study warranted its further development. The
      present study finalizes the HAL and assesses the convergent and construct
      validity, as well as the internal consistency of its definitive version. Three
      questionnaires (HAL, Dutch-Arthritis Impact Measurement Scales 2 and the Impact
      on Participation and Autonomy questionnaire) were completed by 127 patients with
      severe haemophilia (<1% clotting activity), as well as four performance tests
      (button test, 50 metre walking test, timed-up-and-go test and figure-8 walking
      test). After removal of 15 non-informative items from the provisional HAL, three
      components within the questionnaire were identified (upper extremity activities,
      basic lower extremity activities and complex lower extremity activities). The
      internal consistency of these components was high (Cronbach's alpha = 0.93-0.95),
      as was internal consistency for the seven domains of the HAL (alpha = 0.61-0.96).
      The convergent validity of the HAL when compared to the other two questionnaires
      was good (r = 0.47-0.84). The construct validity of the HAL when compared to the
      four performance tests was generally lower (r = 0.23-0.77). The final version of
      the HAL has good internal consistency and convergent validity and gives the
      clinician insight into a patient's self-perceived ability to perform activities
      of daily life. It is likely that self-assessment instruments (questionnaires) and
      performance tests consider different concepts of functional health status and it
      is therefore recommended that both types are included when clinicians assess a
      patient's functional abilities.

PMID- 16409174
TI  - Compliance with treatment and understanding of own disease in patients with
      severe and moderate haemophilia.
AB  - It is well known that teenagers with chronic diseases have problems complying
      with their treatment. The aim of this study was to evaluate the patient's
      knowledge of haemophilia and his compliance to prophylactic treatment, and the
      age at which the patient took over the responsibility for his disease and to
      create educational material for teenagers and adolescents. This was a prospective
      multicentre study performed in Hemophilia Treatment Centres in Scandinavia. A
      total of 108 of 134 patients, between 13 and 25 years completed the
      questionnaire, a response rate of 80%. Eighty-three patients had a severe form of
      haemophilia, 24 patients in moderate form and one patient did not know the
      severity of his disease. Seventy-eight patients were on prophylactic treatment.
      The median age for starting prophylactic treatment was 3.0 years and the median
      age for the patient performing venepuncture was 11.6 years. Sixty-seven of 78
      patients knew that the best time to give prophylactic treatment was in the
      morning. Even though the patients were on prophylactic treatment, 47 of 78
      patients took additional treatment before sports activities. At a mean age of
      14.1 years the patient himself had the responsibility for his disease and
      treatment. In the cohort of 108 patients, 73 were aware of their haemophilia
      heredity. This study shows a rather high degree of knowledge of haemophilia and
      compliance with treatment among the patients but it is of great importance for
      the nurse to continuously improve the patient's compliance and keep him aware of
      the benefit of regular treatment for his future well being.

PMID- 16409175
TI  - Haemophilia in Poland.
AB  - The primary aim of this study was to analyse the data on 2269 haemophilic
      patients in the Polish National Register of Inherited Bleeding Disorders -- 1953
      haemophilia A patients and 316 haemophilia B patients. Haemophilia A occurred in
      1512 families, haemophilia B in 240 families. In the majority of haemophilia A
      and B cases severe haemophilia prevailed (59.7% and 56.6% respectively). In about
      50% of haemophilic patients, no family history of bleeding diathesis was
      reported. For haemophilia A patients the mean age was 30.9 years and for
      haemophilia B patients, 29.2 years. Prevalence of haemophilia in Poland is
      approximately 1:12 300 inhabitants (1:5600 males). The second aim was to describe
      the orthopaedic status of severe haemophilia patients and to relate this status
      to the type of replacement therapy they received prior to the study. Ninety-two
      severe haemophilia patients (median age 26.0 years) were enrolled in the study.
      Right and left knee, elbow and ankle joints were evaluated clinically using the
      Gilbert scale. X-ray examinations were evaluated according to the Pettersson
      scale. Knee joints proved to be most affected. Eighty-four patients (91.3%)
      reported pain. Only one scored 0 on the Gilbert scale, another on the Pettersson
      scale. Thirty-seven per cent of patients used orthopaedic equipment, either
      occasionally or constantly. Twenty-five per cent had a history of orthopaedic
      surgery. Thirty-eight per cent were unemployed with some form of social
      subvention. On-demand treatment was applied. None of the patients received
      primary prophylaxis. The mean consumption of clotting factor concentrates was 68
      054 IU per patient during the 12 months prior to the current study. These results
      indicate that in Poland all severe haemophilia patients above 20 years are
      affected by haemophilic arthropathy.

PMID- 16409176
TI  - Needles and needleless devices for infusion of anti-haemophilic factor
      concentrate: impact on protein structure and function.
AB  - A poor response to the infusion of anti-haemophilic factor (AHF) concentrates
      used to control acute bleeding or prevent haemorrhage during surgery may have
      many causes, including the lack of functional activity of the infused protein
      concentrate. It is generally recommended to follow the manufacturers'
      instructions when administering the factor intravenously. For convenience,
      infusion sets with 23 gauge butterfly needles are packaged with the major brands
      of AHF concentrate. In hospitals, blunt connectors for i.v. infusion are becoming
      more prevalent to reduce the risk of needle stick injuries to both patients and
      hospital staff. The integrity of AHF infused using such devices has not been
      examined. We examined the possibility that passage of complex proteins such as
      AHF through such devices may result in alteration of the protein, rendering it
      inactive. The results presented here suggest that this is not the case; neither
      the structure nor the function of AHF protein products was adversely affected by
      the use of the needleless transfer device (NTD) or the needle types and sizes
      commonly used in clinical practice. Samples of factor VIII and factor IX AHF
      concentrate were passed through the B-D Blunt Plastic Cannula or 23, 27 and 30
      gauge needles. No significant changes in electrophoretic mobility or coagulation
      activity were detected. Samples generally showed slightly increased coagulation
      activity when compared with the control in which the sample was passed directly
      out of the syringe with no device attached. These data indicate that the NTD and
      various needle gauges are acceptable for the infusion of AHF concentrate in a
      clinical setting. Furthermore, the use of small gauge needles has advantages that
      may improve adherence to rigorous factor replacement programmes.

PMID- 16409177
TI  - A rapid multifluorescent polymerase chain reaction for genetic counselling in
      Chinese haemophilia A families.
AB  - Linkage analysis is a widely used strategy for genetic counselling in haemophilia
      A (HA) families. We attempted to develop more informative markers closely linked
      to factor VIII (FVIII) gene and establish a rapid multifluorescent polymerase
      chain reaction (PCR) method with these markers. Five extragenic (DXS15, DXS9901,
      G6PD, DXS1073 and DXS1108) and one intragenic (F8Civs13) markers were examined in
      118 healthy individuals and 12 HA families which had been diagnosed before. Five
      extragenic markers were within an interval of about 1.5 Mb to FVIII gene and
      located on each side of the gene. The expected heterozygote rate (HR) of DXS15,
      DXS9901, G6PD, DXS1073, DXS1108 and F8Civs13 were 74.97%, 79.77%, 56.06%, 59.92%,
      39.97% and 47.61%, while the observed HR were 88.24%, 82.35%, 21.57%, 62.75%,
      35.29% and 52.94%. When six polymorphic markers were combined together, all the
      studied females were informative in at least one of these markers and 29.41% of
      them were detected informative in three markers with the highest frequency. The
      diagnostic rates of DXS15, DXS9901, G6PD, DXS1073, DXS1108 and F8Civs13 in 12
      haemophilia families were 75.00%, 91.67%, 41.67%, 75.00%, 33.33% and 66.67%
      respectively. All the genetic diagnosis was consistent with the result we
      analysed before and no recombination was observed. Family 1 was given as an
      example in this study and was found to be informative in three polymorphic
      markers DXS15, DXS9901 and DXS1073. The patient's sister was detected the same
      allele as the proband, but her male fetus did not inherit the affected allele
      from her, which was consistent with the result of sequencing. It was demonstrated
      that the multifluorescent PCR method established in this study was convenient and
      efficient and can be applied to carrier detection and prenatal diagnosis in HA
      families.

PMID- 16409178
TI  - Hepatitis C at the israeli national hemophilia center.
AB  - Haemophilia patients who received non-virucidally treated large pool clotting
      factors before 1987 have a high rate of chronic hepatitis C viral infection
      (HCV). Some patients are coinfected with HIV. Haemophilia patients and other
      coagulation disorders were treated at one centre since the beginning of the 1970,
      and the Israeli National Hemophilia Center (INHC) was officially founded in 1987.
      To characterize patients with HCV as well as patients with HCV/HIV coinfection at
      the INHC. Patients with haemophilia and other coagulation disorders positive for
      HCV antibodies were evaluated between 2001 and 2004. Demographic data, type and
      severity of coagulation disorder, frequency of coagulation factor usage and
      treatment with concentrated clotting factors prior to 1987 were recorded. Liver
      enzymes, viral load, genotype and data supporting advanced liver disease were
      evaluated. About 179 of 239 haemophilia patients (75%) tested positive for anti
      HCV antibodies. Our cohort consisted of 165 patients in whom clinical,
      biochemical and virological data were available. About 117 patients had active
      HCV infection with HCV-RNA-positive, and 27 were HCV/HIV coinfected. Twenty-one
      patients (13%) persistently tested HCV-RNA-negative, hence were considered to
      clear their HCV infection. There was no former USSR immigrants among HCV/HIV
      coinfected compared with HCV-infected or HCV-RNA-negative groups (0 vs. 30% and
      38%, respectively; P < 0.001). HCV-RNA-negative patients used concentrated
      coagulation factor less frequently than HCV or HCV/HIV-infected patients (48% vs.
      73%; P = 0.023, and 48% vs. 74%; P = 0.043, respectively). The use of
      concentrated clotting factors before 1987 was significantly more frequent in
      HCV/HIV than in either HCV-infected or HCV-RNA-negative patients (96% vs. 49% and
      48%, respectively; P < 0.001). Compared with HCV/HIV subjects, patients with HCV
      monoinfection were characterized by a higher proportion of infection with
      genotype 1 (80% vs. 61%; P = 0.027). The rate of persistently normal liver
      enzymes in these patients was higher (24% vs. 7%; P = 0.05) than in the HCV/HIV
      coinfected patients. Advanced liver disease was significantly more common in
      patients with HCV/HIV-coinfection than in HCV-monoinfected patients (11% vs. 3%;
      P = 0.045). The majority of haemophilia patients are infected with HCV. Viral
      clearance occurred in a minority of these patients. HCV monoinfected and HCV/HIV
      coinfected differ clinically and prognostically.

PMID- 16409180
TI  - Considerations in the evaluation of haemophilia patients for short-term
      prophylactic therapy: a paediatric and adult case study.
AB  - The long-term prophylactic administration of clotting factor concentrate in
      patients with haemophilia reduces bleeding events, slows joint deterioration, and
      improves quality of life. Prophylaxis can also be effective when used short-term
      to prevent or reduce bleeding associated with trauma, surgery, and athletic
      activities. While clinical trials are needed to establish the optimal length of
      prophylaxis following injury, several weeks and possibly months of treatment may
      be needed. Discontinuing therapy prematurely can result in rebleeding in the
      injured area.

PMID- 16409179
TI  - Practice patterns in haemophilia A therapy -- global progress towards optimal
      care.
AB  - This paper reports the findings of a global survey of practice patterns for the
      management of patients with haemophilia A. A total of 147 haemophilia treatment
      centres worldwide responded to the questionnaire, supplying data for 16 115
      patients with haemophilia A. From these responses, 38% (range: 25-48%) of
      patients were under 18 years old. Almost half (47%) of patients were reported to
      have mild or moderate haemophilia A, 48% had severe haemophilia A (no inhibitor)
      and 5% were inhibitor patients. Less than half of patients with severe
      haemophilia A received prophylactic therapy (37%, excluding inhibitor patients)
      and 54% received on-demand treatment; the remaining 9% were inhibitor patients.
      Primary prophylaxis rates for severe haemophilia ranged from 73% in Sweden to 17%
      in the USA. Most respondents (80%) ranked infrequent bleeds as one of the top
      five reasons for not administering prophylactic treatment, followed by venous
      access (60%) and cost (45%). Of patients with severe haemophilia (non-inhibitor),
      32% on primary prophylaxis and 27% on secondary prophylaxis had indwelling
      catheters. Risk of infection and the patient's inability to maintain the line
      were the key concerns cited by nurses relating to venous access. The mean ratio
      of nurses to patients with haemophilia A was 1:69 and nurses felt that they were
      either fully (26%) or mostly (45%) autonomous in assessment and treatment
      decisions. Results from this current survey suggest that worldwide research
      should be continued so as to improve outcomes through the identification of
      optimal treatment protocols for the management of haemophilia A.

PMID- 16409181
TI  - Deep vein thrombosis in a patient with severe haemophilia A.
AB  - A 25-year-old male with severe haemophilia A developed deep vein thrombosis of
      the left upper limb. Venography showed thrombosis of the basilic vein. There was
      no underlying prothrombotic condition. He was successfully treated with low
      molecular weight heparin.

PMID- 16409182
TI  - Long-term prophylaxis with intermediate-purity factor VIII concentrate (Haemate
      P) in a patient with type 3 von Willebrand disease and recurrent gastrointestinal
      bleeding.
AB  - Prophylaxis with von Willebrand factor (VWF)-containing concentrates is
      considered to be a potential approach for patients with von Willebrand disease
      (VWD) and severe bleeding tendency. We report the case of a 57-year-old man with
      type 3 VWD and a history of recurrent melaena. Bleeding frequency and severity
      had progressively increased and the patient showed chronic anaemia and persistent
      haemoglobin in the stools. Endoscopic examinations revealed multiple vascular
      mucosal abnormalities (MVA) of the stomach and large bowel. Photocoagulation of
      some actively bleeding lesions and octreotide did not significantly affect his
      clinical conditions: six red cell transfusions and >400 000 IU of intermediate
      purity factor VIII (FVIII) concentrate (Haemate P) on-demand were needed during
      2002. Prophylaxis with Haemate P 40 IU kg(-1) (102 IU kg(-1) VWF:RCo) thrice
      weekly was associated with improvement of his mean haemoglobin levels, cessation
      of clear-cut melaena and red cell transfusions and reduction of total Haemate P
      requirements (-20% over 2003-04). Prophylaxis with Haemate P is still ongoing
      without any adverse event over a 30-month period. Clinical course and
      pharmacokinetic evaluations led to administer Haemate P each 72-96 h. Possible
      vascular complications were excluded by a careful clinical follow up, as the
      patient suffered from arterial hypertension and diabetes mellitus; thrombophilic
      abnormalities were previously excluded and no signs of abnormal coagulation
      activation or FVIII:C levels >150% were detected thereafter. Long-term
      prophylaxis with Haemate P has been shown to be safe, effective (also in terms of
      quality of life) and cost saving in this patient with severe gastrointestinal
      bleeding due to MVA and VWD.

PMID- 16409184
TI  - Successful induction of immune tolerance by continuous infusion of recombinant
      factor VIII in a haemophilia A patient with high-inhibitor titres.
AB  - The successful and persistent abolition of the inhibitor is of significant
      clinical benefit, as it allows for the restoration of the usual treatment with
      clotting factor concentrate. We describe a successful induction of immune
      tolerance by continuous infusion of recombinant factor VIII (rFVIII) in a 5-year
      old boy with severe haemophilia A and high-responding inhibitor. He had
      previously been subjected to immune tolerance induction (ITI) with rFVIII at 100
      units (U) kg(-1) three times weekly. One year after the beginning of therapy
      tolerance was not achieved and a high titer of inhibitor was detected (15
      Bethesda Units). The patient had a sudden onset of severe neck pain. The
      diagnosis of spinal epidural haematoma was revealed by magnetic resonance
      imaging, and emergency laminectomy with evacuation of the haematoma was required.
      The patient received sequential therapy for surgery first as bolus rFVIII
      injection of 500 U kg(-1) in order to overwhelm the inhibitor and then as
      continuous infusion at 6 to 12 U kg(-1) hour(-1) to avoid bleeding episodes in
      the postoperative period. After the 3 weeks of continuous infusion, the inhibitor
      became undetectable. Thereafter, prophylactic treatment with rFVIII was started
      three times weekly, and the inhibitor has remained undetectable for 6 months.
      The, present case suggests that continuous infusion of rFVIII may be an effective
      therapy to induce immune tolerance.

PMID- 16409183
TI  - Rituximab in the treatment of high responding inhibitors in severe haemophilia A.
AB  - The development of antibodies to factor VIII (FVIII) in severely affected
      haemophilia A patients is a serious complication associated with increased
      morbidity and mortality. Bypassing agents are used to treat acute bleeding
      episodes; however, elimination of the inhibitors can only be achieved with immune
      tolerance therapy (ITT) in 60-80% of cases. High responding (HR) inhibitors are
      more likely to respond to ITT if the titre is decreased to <5 BU over time or in
      selected cases after the administration of immunosuppressive drugs,
      plasmapheresis or immunoabsorption, techniques difficult to apply in children.
      Anti-CD20 (rituximab), a monoclonal antibody, was given as an alternative
      treatment in two haemophilic children with HR inhibitors and impaired quality of
      life, due to recurrent haemarthrosis. Rituximab was given at the dose of 375 mg
      m(-2), once weekly for four consecutive weeks. Both patients showed a partial
      response to rituximab reducing the inhibitor titre to <5 BU, thus facilitating
      ITT initiation; however, only the older patient eradicated the inhibitor within
      21 days after application of ITT. The second patient, despite depletion of B
      cells, did not respond to ITT. No long-term side effects have been observed in
      both patients for a follow-up period of 20 and 18 months respectively. In
      conclusion, rituximab appears to be an alternative effective therapy to rapidly
      reduce or eliminate the inhibitor in selected cases of severely affected
      haemophiliacs before further proceeding to ITT. However, the dose and appropriate
      schedule, as well as long-term side effects need further investigation.

PMID- 16409185
TI  - Anasarca improved by extracorporeal ultrafiltration through an internal shunt in
      a case of severe haemophilia B with inhibitor and steroid-resistant nephrotic
      syndrome.
AB  - A patient suffering from severe haemophilia B with factor IX inhibitor developed
      steroid-resistant nephrotic syndrome. As a result of switching to activated anti
      inhibitor coagulant complex (activated prothrombin complex concentrate) agent,
      FEIBA, bleeding was controlled and internal shunt placement was successful,
      leading to control of bleeding during extracorporeal ultrafiltration (ECU)
      therapy. We report this case where regular ECU therapy became possible and as a
      result anasarca was controlled.

PMID- 16409186
TI  - Inhibitor challenges in the paediatric setting.

PMID- 16409187
TI  - Cost minimization model for treatment of minor bleeding episodes in inhibitor
      patients -- methodological issues.

PMID- 16409188
TI  - Higher recovery of factor VIII (FVIII) with intermediate FVIII/von Willebrand
      factor concentrate than with recombinant FVIII in a haemophilia A patient with an
      inhibitor.

PMID- 16409189
TI  - Allergen-specific sublingual immunotherapy: less mystic, more scientific.

PMID- 16409190
TI  - Immune mechanisms of allergen-specific sublingual immunotherapy.
AB  - Sublingual immunotherapy has been shown in some clinical studies to modulate
      allergen-specific antibody responses [with a decrease in the immunoglobulin
      E/immunoglobulin G4 (IgE/IgG4) ratio] and to reduce the recruitment and
      activation of proinflammatory cells in target mucosa. Whereas a central paradigm
      for successful immunotherapy has been to reorient the pattern of allergen
      specific T-cell responses in atopic patients from a T helper (Th)2 to Th1
      profile, there is currently a growing interest in eliciting regulatory T cells,
      capable of downregulating both Th1 and Th2 responses through the production of
      interleukin (IL)-10 and/or transforming growth factor (TGF)-beta. We discuss
      herein immune mechanisms involved during allergen-specific sublingual
      immunotherapy (SLIT), in comparison with subcutaneous immunotherapy. During SLIT,
      the allergen is captured within the oral mucosa by Langerhans-like dendritic
      cells expressing high-affinity IgE receptors, producing IL-10 and TGF-beta, and
      upregulating indoleamine dioxygenase (IDO), suggesting that such cells are prone
      to induce tolerance. The oral mucosa contains limited number of proinflammatory
      cells, such as mast cells, thereby explaining the well-established safety profile
      of SLIT. In this context, second-generation vaccines based on recombinant
      allergens in a native conformation formulated with adjuvants are designed to
      target Langerhans-like cells in the sublingual mucosa, with the aim to induce
      allergen-specific regulatory T cells. Importantly, such recombinant vaccines
      should facilitate the identification of biological markers of SLIT efficacy in
      humans.

PMID- 16409191
TI  - Comparative analysis of nasal and oral mucosa dendritic cells.
AB  - BACKGROUND: Mucosal dendritic cells (DC) play a crucial role in tolerance
      induction as seen in mucosal immunotherapy of atopic diseases. Nevertheless
      little is known about the phenotypical differences of oral and nasal mucosal DC
      (nmDC). Recently, we could show that oral mucosal myeloid CD1a(+) DC (omDC)
      differ from their skin counterparts especially by the expression of high affinity
      receptor for immunoglobulin E (IgE; FcepsilonRI). However, expression pattern of
      FcepsilonRI and phenotypical characteristics of CD1a(+) nmDC have not been
      elucidated in detailed yet. METHODS: We performed detailed phenotypical
      comparison of nmDC and omDC of atopic and nonatopic individuals. RESULTS: As
      reported for omDC, FcepsilonRI on nmDC of atopic donors was elevated and mostly
      occupied by IgE while FcepsilonRI was present only in low amounts on nmDC of
      nonatopic donors. Nevertheless, the highest FcepsilonRI expression has been
      observed on omDC. Furthermore, significant amounts of costimulatory molecules
      CD40, CD80 and CD86 could be detected on nmDC that expressed more CD80 compared
      with omDC. Moreover, nmDC displayed less major histocompatability complex (MHC)
      class I and II molecules than omDC. In addition, nmDC expressed more C-type
      lectins CD205, CD206 as well as myeloid marker CD11b while omDC displayed
      increased expression of CD207 and lipopolysaccharide (LPS) receptor CD14.
      CONCLUSION: Together these data imply that nmDC phenotypical differ from omDC
      which might result in diverse functional properties and might be of relevance for
      selecting routes for immunotherapy of atopic diseases. Moreover these data
      provide a basis for further studies investigating immunological mechanisms
      underlying mucosal immunotherapy.

PMID- 16409192
TI  - The role of Foxp3+ T cells in long-term efficacy of prophylactic and therapeutic
      mucosal tolerance induction in mice.
AB  - BACKGROUND: Mucosal tolerance induction is suggested as treatment strategy for
      allergic diseases. Using a murine model of birch pollen (BP) allergy we
      investigated the long-term efficacy and the underlying mechanisms of mucosal
      tolerance induction with two structurally different molecules in a prophylactic
      and in a therapeutic set-up. METHODS: The three-dimensional major BP allergen Bet
      v 1 or a nonconformational hypoallergenic fragment thereof was intranasally
      applied before (prophylaxis) or after sensitization (therapy). RESULTS: In the
      prophylactic application both the Bet v 1 allergen and the fragment prevented
      allergic sensitization, and this effect lasted for 1 year. In the therapeutic
      approach established allergic immune responses were also suppressed after
      treatment with either of the molecules. However, a long-lasting curative effect
      (6 months) was only achieved with the Bet v 1 allergen but not with the Bet v 1
      fragment. Real-time reverse transcriptase polymerase chain reaction (RT-PCR)
      analysis of splenocytes revealed that tolerance induction with the Bet v 1
      allergen was associated with enhanced expression of transforming growth factor
      (TGF)-beta, interleukin (IL)-10, and Foxp3 mRNA in CD4+ T cells, whereas
      treatment with the fragment led to the induction of either Foxp3 (prophylaxis) or
      IL-10 (therapy) alone. CONCLUSION: From these data we concluded (i) that the
      mechanisms underlying peripheral tolerance are linked to the conformation of the
      antigen, (ii) that mucosal tolerance is mediated by separate regulatory cell
      subsets, and (iii) that the long-term efficacy of immunosuppression is associated
      with the presence of Foxp3+ T cells.

PMID- 16409193
TI  - Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Sublingual treatment of grass pollen induced rhinoconjunctivitis
      might provide easier access to specific immunotherapy (SIT) and minimize the risk
      of serious adverse events (AEs) compared to subcutaneous SIT. AIM OF THE STUDY:
      To identify a safe dose range for once-daily administration of a grass allergen
      tablet in participants with grass pollen induced seasonal rhinoconjunctivitis.
      METHODS: A randomized, double blind, placebo-controlled Phase I trial was
      conducted outside the grass pollen season. Seven dosage groups [25,000, 75,000,
      150,000, 300,000, 500,000, 750,000, or 1,000,000 standardized quality tablet (SQ
      T)], consisting of 12 participants randomized either to active treatment or
      placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at
      intervals of approximately 1 week to allow for intermittent safety reviews.
      RESULTS: The grass allergen tablet did not cause any serious, systemic or
      significant (leading to withdrawal) AEs. The overall incidence of AEs was 74%
      (1,013 events); all of mild or moderate intensity and most considered treatment
      related. The most frequently reported treatment-related AEs, including irritation
      of the throat, and itching sensations in the mouth and ears, increased with dose.
      These were primarily mild in intensity, started shortly after medication intake
      and lasted for minutes to a few hours maximum. Objective oral findings were also
      dose-dependent. No clinically significant observations were found in safety
      laboratory, vital signs and 12-lead ECG. CONCLUSIONS: A sublingual grass allergen
      tablet in doses up to 1,000,000 SQ-T daily caused no serious or systemic AEs
      displaying a safety profile that allows further investigation as once-daily self
      medication.

PMID- 16409194
TI  - Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics
      with rhinoconjunctivitis.
AB  - BACKGROUND: The best way to prevent allergy symptoms is to treat the allergic
      condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T
      (Grazax, Phleum pratense, ALK-Abello) is safe and efficacious in
      rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma,
      we aimed to confirm safety and efficacy in grass allergic subjects with asthma
      and rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled,
      multicentre trial was performed 10-14 weeks prior to and during the grass pollen
      season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets
      or placebo. The primary end points were average asthma medication and symptom
      scores during the grass pollen season, and secondary variables were average
      rhinoconjunctivitis symptom and medication scores during the grass pollen season.
      Additionally, number of well days was defined post hoc. RESULTS: Differences in
      asthma medication and symptom scores between the treatment groups were
      negligible. The mean difference in asthma medication score was below 0.1 and 0.3
      for asthma symptom score [a single inhalation of salbutamol (200 microg) was
      scored 2]. No serious adverse events were reported. A reduction in
      rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036)
      reduction in medication score was found in the grass pollen season for subjects
      treated with the grass allergen tablet compared with placebo. Well days increased
      by 54% (P = 0.002). CONCLUSIONS: Self-administration of the grass allergen tablet
      was safe. The treatment did not impair asthma control and confirmed considerable
      symptom prevention and reduced medication use. It addresses the allergic
      condition and represents a baseline treatment for grass pollen allergy.

PMID- 16409195
TI  - A double-blind, placebo-controlled study of house dust mite immunotherapy in
      Chinese asthmatic patients.
AB  - BACKGROUND: The purpose of this study was to determine if house dust mite
      immunotherapy with Alutard SQ is effective in improving symptom control and
      reducing rescue medication use in Chinese patients with mild to moderate allergic
      asthma. METHODS: This is a double-blind, placebo-controlled study involving 132
      asthmatic subjects aged 6-45 years recruited from three different regions of
      Mainland China. Subjects were given a 52-week course of immunotherapy with
      Dermatophagoides pteronyssinus extract (Alutard Der p, ALK-Abello, Horsholm,
      Denmark) or placebo while their dose of inhaled corticosteroids (ICS) was
      maintained. RESULTS: 129 subjects (64 in active group) completed the study. The
      symptom scores began to diverge at week 29 with the immunotherapy group showing a
      significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a
      significant decline in symptom (P = 0.002) and medication (P = 0.007) scores
      during the second half of the treatment period. Both groups showed significant
      improvement in peak flow rate and bronchial hyperresponsiveness. Serum eosinophil
      cationic protein (ECP) also decreased in both groups of subjects, but peripheral
      blood eosinophil count remained unchanged. Skin test response decreased in
      actively treated subjects only, but Der p-specific immunoglobulin E (IgE)
      remained unchanged. Immunotherapy resulted in a significantly greater improvement
      in self-evaluation scores (P < 0.01). CONCLUSIONS: One year treatment with
      Alutard SQ house dust mite immunotherapy significantly reduced symptoms and
      medication use in asthmatic subjects. This was associated with a greater
      subjective improvement in asthma control.

PMID- 16409196
TI  - Twelve-year follow-up after discontinuation of preseasonal grass pollen
      immunotherapy in childhood.
AB  - BACKGROUND: In a previous controlled study, we demonstrated that preseasonal
      grass pollen immunotherapy for 3 years was effective in children. Moreover, a
      significant clinical benefit could still be observed 6 years after
      discontinuation of specific immunotherapy (SIT). In the current study, we
      examined the same group of patients again to investigate whether there is a
      prolonged benefit 12 years after SIT is stopped. METHODS: Twenty-two patients
      with previous SIT (from 1989 through 1991) or standardized seasonal
      pharmacotherapy only were prospectively followed during the grass pollen season
      of 2003. Primary end points were symptom score, medication use, and combined
      symptom and medication score. In addition, skin prick test reactivity,
      development of new sensitizations, and prevalence of seasonal asthma were
      evaluated. RESULTS: Total hay fever symptom score (P < 0.03), use of medication
      (P < 0.05), and combined symptom and medication score (P < 0.03) remained lower
      in patients with previous SIT when compared with the control group. Decreased
      immediate skin response to grass pollen returned 12 years after cessation of SIT.
      The percentage of new sensitization, however, continued to be significantly
      smaller in patients with previous SIT (58%) compared with the controls (100%, P <
      0.05). There was a tendency for lower prevalence of seasonal asthma in the post
      SIT group (P = 0.08). CONCLUSION: This prospective controlled prolonged follow-up
      study demonstrates the ongoing clinical benefit 12 years after discontinuation of
      SIT. Furthermore, the reduction in onset of new sensitization, which was found 6
      years after discontinuation of SIT, is sustained 6 years later.

PMID- 16409197
TI  - Usefulness of specific immunotherapy in patients with atopic dermatitis and
      allergic sensitization to house dust mites: a multi-centre, randomized, dose
      response study.
AB  - BACKGROUND: The effect of specific immunotherapy (SIT) on eczema in atopic
      dermatitis is not known. Therefore, a multi-centre, randomized dose-response
      trial, double-blind with respect to the efficacy of a biologically standardized
      depot house dust mite preparation was performed. METHODS: Eighty-nine adults with
      a chronic course of atopic dermatitis, SCORAD >or=40 and allergic sensitization
      to house dust mites [CAP-FEIA >or=3] were included, of whom 51 completed the
      study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides
      pteronyssinus/D. farinae) applying maintenance doses of 20, 2,000 and 20,000 SQ-U
      in weekly intervals for 1 year. The main outcome measures addressed the change of
      the SCORAD as average of the values after 9 and 12 months of SIT in comparison
      with the value at baseline. RESULTS: The SCORAD declined in the three dose groups
      in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was
      significantly lower in the two high-dose groups (2,000, 20,000 SQ-U) compared
      with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The
      use of topical corticosteroids was significantly reduced with higher doses (P =
      0.0007, Mantel-Haenszel chi-square test). CONCLUSIONS: Allergen-SIT for 1 year
      with a house dust mite preparation is able to improve the eczema in patients with
      atopic dermatitis who are sensitized to house dust mite allergens and reduces the
      need for topical corticosteroids. SIT may be valuable in the treatment of this
      chronic skin disease.

PMID- 16409198
TI  - IgE reactivity to latex allergens among sensitized healthcare workers before and
      after immunotherapy with latex.
AB  - BACKGROUND: New IgE sensitizations to proteins in allergen extracts have been
      shown to occur during allergen-specific immunotherapy (IT). METHODS: Twenty-four
      healthcare workers (HCWs) -- patients included in a latex IT study -- were
      analysed, 16 in active treatment and eight in placebo. Sera were obtained at
      baseline and after 6 months of IT and analysed with immunoblotting and CAP System
      with eight single recombinant latex allergens (rHev b 1, 3, 5, 6.01, 8, 9, 10,
      11, and a mix of rHev b1, 5, 6.01 and 8). RESULTS: After IT with latex, three
      patients in the active treatment group had new IgE sensitizations, one to Hev b
      5, one to Hev b 11 and another to Hev b 6.01. No other significant variation in
      mean of specific IgE to latex or recombinant allergens were observed in patients
      who received placebo or active treatment. A significant (P = 0.012) negative
      correlation (-0.72) was observed between maximal tolerated dose and specific IgE
      to Hev b 6.01 at baseline. After IT, immunoblot analysis demonstrated a
      significant increase in IgE binding in a band of approximately 22 kDa (P = 0.032)
      that may correspond to Hev b 6.01. New or more intense bands appeared in seven
      patients of the active group, while in three subjects a reduction was observed.
      CONCLUSIONS: Hev b 6.01 seems to be the most relevant latex allergen in HCWs. New
      or more intense IgE binding to latex allergenic components occurs during latex
      immunotherapy. However, the levels of specific IgE against these new components
      are low and do not seem to have clinical relevance.

PMID- 16409199
TI  - Haemodialysis-associated anaphylactic and anaphylactoid reactions.
AB  - Anaphylactic and anaphylactoid reactions related to haemodialysis have been
      increasingly described for almost 3 decades. The majority of these cases used to
      occur with ethylene oxide sterilized, and complement-activating cellulose
      membranes. However, a considerable number of publications have focused on
      polyacrylonitrile AN69 high flux membranes, angiotensin converting enzyme
      inhibitors and iron as other important causes of potentially severe haemodialysis
      related anaphylactoid reactions. Clinical manifestations vary considerably and
      generally do not allow differentiation between IgE-mediated anaphylaxis and
      anaphylactoid reactions (e.g. from nonspecific mediator release). Successful
      management of these patients requires multidisciplinary approach and involves
      prompt recognition and treatment by the attending physician, and identification
      of the offending agent(s) with subsequent avoidance of the incriminated
      compound(s). This review focuses on some major causes of anaphylactoid and
      anaphylactic reactions during haemodialysis. Special consideration is given to
      the therapeutic and diagnostic approach.

PMID- 16409200
TI  - European birth cohort studies on asthma and atopic diseases: I. Comparison of
      study designs -- a GALEN initiative.
AB  - BACKGROUND: The reasons for the rise in asthma and allergies remain unclear. To
      identify risk or protective factors, it is essential to carry out longitudinal
      epidemiological studies, preferably birth cohort studies. In Europe, several
      birth cohort studies on asthma and atopic diseases have been initiated over the
      last two decades. AIM: One of the work packages within the Global Allergy and
      Asthma European Network (GA(2)LEN) project was designed to identify and compare
      European birth cohorts on asthma and atopic diseases. The present review (part I)
      describes their objectives, study settings, recruitment process and follow-up
      rates. A subsequent review (part II) will compare outcome and exposure
      parameters. METHODS: For each birth cohort, we collected detailed information
      regarding recruitment process, study setting, baseline data (pregnancy, birth,
      parents/siblings) as well as follow-up rates, outcome and exposure parameters at
      each time point. RESULTS: We identified and assessed 18 European birth cohorts on
      asthma, allergic rhinitis and eczema. Six of these studies also focused on food
      allergies. The birth cohorts were mostly initiated in the 1990s with
      predominantly urban/metropolitan settings. Many studies were able to maintain
      high follow-up rates, even after five or more years. CONCLUSIONS: Due to the
      unique cooperation within the GA(2)LEN project a common database was established
      containing study characteristics of European birth cohorts on asthma and atopic
      diseases. This can be used as a basis for evaluating the possibility to pool data
      and perform meta-analyses, as well as to recommend criteria for conducting future
      birth cohorts.

PMID- 16409201
TI  - Risk factors for asthma in young adults: a co-twin control study.
AB  - BACKGROUND: The liability to asthma is influenced both by genetic and
      environmental factors. The objective of this study was to identify risk factors
      for asthma in young adult twin pairs during an 8-year period. METHODS: From the
      birth cohorts 1953-1982 of the Danish Twin Registry, 6,090 twin pairs who were
      initially unaffected with respect to asthma at a nationwide questionnaire-based
      study in 1994 participated in a similar follow-up study in 2002. Subjects were
      regarded incident asthma cases when responding affirmatively to the question 'Do
      you have, or have you ever had asthma'? in 2002. Pairs in which only one twin
      developed asthma -- discordant pairs -- were identified and conditional logistic
      regression was applied to detect effects of risk factors. RESULTS: A total of 126
      monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In
      MZ twins hay fever (OR = 3.16, 95% CI: 1.29-7.73, P = 0.007) and exercise (OR for
      inactivity = 0.35, 95% CI: 0.13-0.91, P = 0.023) were significantly associated
      with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44-4.13, P =
      0.001), eczema (OR = 1.96, 95% CI: 1.02-3.78, P = 0.040), female sex (OR between
      males and females = 0.54, 95% CI: 0.36-0.80, P = 0.002), and increasing levels of
      body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02-1.20, P = 0.009) were
      significant predictors of asthma. CONCLUSIONS: Hay fever, eczema, female sex,
      exercise and increasing levels of BMI were risk factors for asthma in young
      adults. The different risk profile observed in MZ twins compared with DZ twins
      may reflect an underlying genetic vulnerability shared between those risk factors
      and asthma.

PMID- 16409203
TI  - Association between interleukin-1 receptor antagonist gene and asthma-related
      traits in a German adult population.
AB  - BACKGROUND: A recent study in German and Italian families associated variants in
      the interleukin-1 receptor antagonist (IL1RA) gene with asthma. The aim of the
      present study was to further investigate the role of single nucleotide
      polymorphisms (SNPs) in the IL1RA gene in the development of atopy and lifelong
      asthma in a population-based study. METHODS: DNA samples from the German centres
      of the European Community Respiratory Health Survey were analysed for genetic
      variants in the IL1RA gene and the development of asthma, atopy and bronchial
      hyperreactivity. RESULTS: Carriers of the rare G allele of SNP rs447713 had a
      significantly increased risk of developing asthma (P = 0.0013) and allergic
      sensitization (P = 0.0119). Carriers of the rare C allele of SNP rs3087271 had an
      increased risk of asthma (P = 0.0227) and high immunoglobulin E (IgE) levels (P =
      0.0232). A haplotype built from eight SNPs in the IL1RA gene (A-C-A-G-A-C-G-A)
      was associated with a higher prevalence of asthma (P = 0.007) and high total IgE
      (P = 0.02). Bronchial hyperreactivity was positively associated with the
      haplotype A-C-G-G-A-C-G-C (P = 0.02) and negatively with the A-C-G-G-A-C-T-C (P =
      0.03). CONCLUSION: A previously described association between IL1RA and asthma in
      families could be reproduced in a population-based sample. The genetic variants
      of IL1RA gene do not to seem to affect asthma alone, but to act as modulators of
      asthma-related traits as well, where different haplotypes drive the development
      of different phenotypes.

PMID- 16409202
TI  - The -675 4G/5G plasminogen activator inhibitor-1 promoter polymorphism in house
      dust mite-sensitive allergic asthma patients.
AB  - BACKGROUND: Plasminogen activator inhibitor (PAI)-1 plays an important role in
      inflammation and tissue remodeling. Recently, the -675 4G/5G PAI-1 polymorphism
      has been linked with asthma. OBJECTIVE: This study was undertaken to evaluate
      associations of the -675 4G/5G PAI-1 polymorphism with functional and immunologic
      parameters of newly diagnosed house dust mite-sensitive allergic asthmatics (HDM
      AAs). METHODS: This study was performed in 127 HDM-AAs, who responded with at
      least 20% fall of forced expiratory volume during the first second (FEV(1)) to a
      bronchial challenge with Dermatophagoides pteronyssinus allergen and during the
      follow up observation fulfilled GINA criteria for mild-moderate asthma. About 89
      healthy control nonatopic subjects (HCs) were used as controls. RESULTS: The
      frequency of 4G allele was greater in HDM-AAs (0.69; 95% CI: 0.62-0.76) than in
      HCs (0.55; 95% CI: 0.48-0.62; P = 0.0034). The PAI-1 polymorphism was associated
      with an increased risk of HDM-AA; adjusted for sex and age odds ratio was 2.62;
      (95% CI: 1.16-5.92) for 4G/5G genotype and 3.48 (95% CI: 1.54-7.89) for 4G/4G
      genotype compared with 5G/5G genotype. Total serum immunoglobulin E (tsIgE) level
      in 4G/4G homozygotes (557 +/- 343 kU/l) was significantly greater than in 5G/5G
      homozygotes (241 +/- 288 kU/l; P < 0.001). Both nonspecific and allergen-specific
      bronchial reactivities were greater in 4G/4G homozygotes than in 5G/5G
      homozygotes. 4G/4G genotype was associated with significantly higher morning
      plasma PAI-1 concentration in HDM-AAs and HCs. Morning plasma PAI-1 concentration
      correlated significantly with log(PC20) (r = -0.39; P = 0.0001) and with
      log(tsIgE) (r = 0.247; P = 0.0117). CONCLUSION: These results support the
      hypothesis linking the 4G/4G PAI-1 genotype with an increased risk of allergic
      asthma, bronchial hyperreactivity, and increased tsIgE levels.

PMID- 16409204
TI  - Variance components analyses of multiple asthma traits in a large sample of
      Australian families ascertained through a twin proband.
AB  - BACKGROUND: Intermediate phenotypes are often measured as a proxy for asthma. It
      is largely unclear to what extent the same set of environmental or genetic
      factors regulate these traits. OBJECTIVE: Estimate the environmental and genetic
      correlations between self-reported and clinical asthma traits. METHODS: A total
      of 3,073 subjects from 802 families were ascertained through a twin proband.
      Traits measured included self-reported asthma, airway histamine responsiveness
      (AHR), skin prick response to common allergens including house dust mite
      (Dermatophagoides pteronyssinus [D. pter]), baseline lung function, total serum
      immunoglobulin E (IgE) and eosinophilia. Bivariate and multivariate analyses of
      eight traits were performed with adjustment for ascertainment and significant
      covariates. RESULTS: Overall 2,716 participants completed an asthma questionnaire
      and 2,087 were clinically tested, including 1,289 self-reported asthmatics (92%
      previously diagnosed by a doctor). Asthma, AHR, markers of allergic sensitization
      and eosinophilia had significant environmental correlations with each other
      (range: 0.23-0.89). Baseline forced expiratory volume in 1 s (FEV(1)) showed low
      environmental correlations with most traits. Fewer genetic correlations were
      significantly different from zero. Phenotypes with greatest genetic similarity
      were asthma and atopy (0.46), IgE and eosinophilia (0.44), AHR and D. pter (0.43)
      and AHR and airway obstruction (-0.43). Traits with greatest genetic
      dissimilarity were FEV(1) and atopy (0.05), airway obstruction and IgE (0.07) and
      FEV(1) and D. pter (0.11). CONCLUSION: These results suggest that the same set of
      environmental factors regulates the variation of many asthma traits. In addition,
      although most traits are regulated to great extent by specific genetic factors,
      there is still some degree of genetic overlap that could be exploited by
      multivariate linkage approaches.

PMID- 16409205
TI  - The effect of beta2-adrenoceptor haplotypes on bronchial hyper-responsiveness in
      patients with asthma.
AB  - BACKGROUND: The beta2-adrenoceptor exhibits genetic polymorphism which may be
      clinically relevant in terms of treatment response or bronchial hyper
      responsiveness (BHR). The combined effect of these genotypes, or the haplotype,
      has not been fully characterized in terms of BHR. METHODS: We performed a
      retrospective analysis of the effects of haplotypes of amino acid substitution at
      position 16 (Gly/Arg) and position 27 (Gln/Glu) on spirometry and BHR to
      methacholine and adenosine monophosphate (AMP) in 594 asthmatic patients.
      RESULTS: There was a significant (P < 0.05) overall effect for forced expiratory
      volume (FEV(1)) but not after correction for steroid dose and atopic status.
      There were no significant differences for BHR to methacholine or AMP between the
      different haplotypes and no difference between the numbers of patients with or
      without clinically relevant BHR. Methacholine PD20 geometric mean-fold difference
      was 1.63 (95% CI: 0.95-2.80) between Arg-Arg/Gln-Gln and Gly-Gly/Gln-Gln and 1.26
      (95% CI: 0.75-2.11) between Gly-Gly/Gln-Gln and Gly-Gly/Glu-Glu. CONCLUSIONS: The
      degree of BHR to indirect and direct stimuli does not differ between beta2
      adrenoceptor haplotypes, and haplotypes cannot be used to predict BHR in patients
      presenting with asthma. Although beta2-adrenoceptor haplotypes do not predict BHR
      they may be important in predicting response to bronchodilator therapy.

PMID- 16409206
TI  - Normal C1 inhibitor mRNA expression level in type I hereditary angioedema
      patients: newly found C1 inhibitor gene mutations.
AB  - BACKGROUND: C1 esterase inhibitor (C1INH) plays a key role in the classical
      pathway of the complement cascade. Mutations in this gene cause a decreased level
      of antigenic (type I hereditary angioedema, HAE) or functional (type II HAE)
      C1INH. OBJECTIVE: To find novel mutations in C1INH and evaluate the expression of
      C1INH gene in HAE patients. METHODS: Direct sequencing mutation analysis was
      performed for genomic DNA from three unrelated families (14 HAE patients and 18
      family members). Genomic DNA from one family was also analyzed for larger genomic
      rearrangements, using Southern blotting analysis. We used real-time quantitative
      polymerase chain reaction (PCR) to evaluate C1INH mRNA expression level. RESULTS:
      Four mutations in exons (2,311 T-->C, 14,034 G-->A, 16,830 G-->A, and 16,979
      16,980 G insertion) and four in introns (738 G-->A, 8,531 A-->G, 14,254 A-->G,
      and 14,337-14,378 TT deletion) were found. Interestingly, all of the nine
      patients in one family share the same mutation of Gly345Arg (14,034 G-->A) in the
      seventh exon. In another family, a single base mutation near the splice site
      (14,254 A-->G) was found in all of the three patients. In the last family,
      although a significant mutation was not found by direct sequencing, patients
      showed an abnormal 16 kb fragment in addition to the normal allele (21 kb Bcl I
      fragment). The C1INH mRNA expression of HAE patients in two families was not
      significantly different compared with that of normal controls. CONCLUSION: The
      two novel exonal mutations (G-->A and A-->G) and one large gene deletion were
      associated with the clinical phenotypes of HAE. Considering the normal C1INH mRNA
      levels but below normal protein levels in two families, their phenotypes would be
      associated with the post-translational defect.

PMID- 16409207
TI  - Polymorphisms of the GSTM1 and GSTT1 genes in patients with allergic diseases in
      the Czech population.
AB  - BACKGROUND: Allergic diseases belong to the most common chronic disorders
      affecting mankind and their prevalence in population is increasing. Several
      studies have indicated that oxidative stress impairs pulmonary function and makes
      existing asthma worse. Members of the glutathione-S-transferase (GST) superfamily
      of genes are important in protection of cells from reactive oxygen species. AIMS
      OF THE STUDY: Relationships among allergic diseases including asthma and
      variations in the GST mu (GSTM1) and GST theta (GSTT1) genes were investigated in
      1,006 Caucasian subjects. METHODS: The multiplex polymerase chain reaction
      protocol was used for simultaneous amplification of both genes for molecular
      analysis. Genotype frequencies among patients and controls were assessed and the
      associations of the genotypes with intermediary phenotypes of allergy were
      statistically determined. RESULTS: The frequencies of GST null genotypes did not
      differ significantly between patients with allergic diseases (or asthma alone)
      and healthy controls. However, when compared with patients homozygous or
      heterozygous for GSTM1 functional allele, asthmatics carrying both GSTM1 null
      alleles displayed significantly worse lung function, assessed by forced
      expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) ratio (Tiffenau
      index), (P < 0.01). CONCLUSIONS: Genetic polymorphisms of the GSTM1 and GSTT1
      genes, both individually and in combination, were not associated with the
      development of allergic diseases including asthma in the Czech population, the
      GSTM1 gene variability, however, may influence lung functions in our asthmatics.

PMID- 16409208
TI  - Insect sting anoxic encephalopathy after stopping venom immunotherapy.

PMID- 16409209
TI  - Ranitidine-induced anaphylaxis: detection of serum specific IgE antibody.

PMID- 16409210
TI  - Urticaria-angioedema reaction caused by propafenone.

PMID- 16409211
TI  - Is ethanol-induced bronchospasm an inflammation-driven event?

PMID- 16409213
TI  - Sexual health inquiry and support is a primary care priority.
AB  - The World Health Organization defines sexual health as "a state of physical,
      emotional, mental and sexual well-being related to sexuality." This broad
      definition goes beyond simply inquiring about sexual dysfunction and ideally fits
      the model of patient-centered primary care. As we observe that sexual health and
      physical health are often closely related, discussions about sexual activity can
      be very revealing. Sexual intimacy appears positively related to loving
      relationship satisfaction and stability. Sexual problems have a clear negative
      impact on both the quality of life and emotional state regardless of age.
      Learning about specific sexual dysfunctions among men can reveal a variety of as
      yet-undiagnosed comorbid pathologic conditions such as: (i) depression and other
      emotional illnesses; (ii) psychosocial stress; (iii) actual cardiovascular
      disease as well as related risk factors such as hypertension, diabetes, and/or
      hyperlipidemia; (iv) hyperprolactinemia; and (v) low serum testosterone. Specific
      sexual dysfunctions among women can reveal pathologic conditions such as: (i)
      depression and other adverse imitational and psychosocial conditions; (ii) low
      serum estrogen or testosterone; and/or (iii) vaginal or pelvic disorders. A
      discussion about sexual health can be accomplished efficiently in a primary care
      office with the inquiring clinician having the option to deal with any sexual
      problems and dysfunctions directly, or to refer the patient to an appropriate
      specialized care source.

PMID- 16409214
TI  - Ocular safety in patients using sildenafil citrate therapy for erectile
      dysfunction.
AB  - Sildenafil citrate improves erectile function in men with erectile dysfunction
      (ED) by selectively inhibiting cyclic guanosine monophosphate (cGMP)-specific
      phosphodiesterase type 5 (PDE5), which is present in all vascular tissue.
      Sildenafil also has a weaker inhibitory action on PDE6, located in the rod and
      cone photoreceptors. Modest, transient visual symptoms, typically blue tinge to
      vision, increased brightness of lights, and blurry vision, have been reported
      with sildenafil use and occur more frequently at higher doses. Visual function
      studies in healthy subjects and in patients with eye disease suggest that
      sildenafil does not affect visual acuity, visual fields, and contrast
      sensitivity. Transient, mild impairment of color discrimination can occur around
      the time of peak plasma levels. Spontaneous postmarketing reports of visual
      adverse events, including nonarteritic anterior ischemic optic neuropathy
      (NAION), have been reported during the 7 years that sildenafil has been
      prescribed to more than 27 million men worldwide. However, because men with ED
      frequently have vascular risk factors that may also put them at increased risk
      for NAION, a causal relationship is difficult to establish. No consistent pattern
      has emerged to suggest any long-term effect of sildenafil on the retina or other
      structures of the eye or on the ocular circulation.

PMID- 16409216
TI  - Sexual communication skills in residency training: the Robert Wood Johnson model.
AB  - Few medical schools or residency programs offer adequate training in sexual
      medicine. Using the experience gained in our long-standing program in human
      sexuality for medical students, we have pilot tested a half-day intensive
      workshop curriculum for residents that focuses on sexual communication skills and
      management of sexual problems. Unlike our medical school program, this residency
      course was offered on an elective, one-day basis. The current report describes
      the successful implementation of our pilot program with 46 medical residents from
      subspecialty and primary care residency programs. Before the workshop, 22 (48%)
      residents indicated that they were uncomfortable with open discussion of sexual
      issues and would not feel comfortable in addressing the topic with their
      patients. A number of factors were identified as barriers to communication,
      including lack of time, inadequate training, and personal discomfort. After the
      workshop, the participants rated themselves as more comfortable with the topic
      and as more likely to address sexual issues with their patients. The participants
      evaluated the workshop positively overall and responded well to the interactive
      format and audience-response components. Most of the participants showed interest
      and willingness to participate in further training in sexual medicine skills. Our
      program offers a model for training of residents in communication skills and
      management of sexual problems. The difficulties in implementation and overcoming
      institutional barriers to curriculum reform are addressed.

PMID- 16409215
TI  - The second Princeton consensus on sexual dysfunction and cardiac risk: new
      guidelines for sexual medicine.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent disorder associated
      with a significant burden of illness. The prevalence and incidence of ED are
      strongly age-related, affecting more than half of men >60 years. The first
      Princeton Consensus Conference (Princeton I) in 1999 developed guidelines for
      safe management of cardiac patients regarding sexual activity and the treatment
      of ED. AIM: The second conference (Princeton II) was convened to update the
      recommendations based on the expanding knowledge base and new treatments
      available. This article reviews and expands on the Princeton II guidelines to
      address sexual dysfunction and cardiac risk. METHODS: A consensus panel of
      experts reviewed recent multinational studies in safety and drug interaction data
      for three phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil,
      vardenafil), with emphasis on the safety of these agents in men with ED and
      concomitant cardiovascular disease. RESULTS: Erectile dysfunction is an early
      symptom or harbinger of cardiovascular disease, due to the common risk factors
      and pathophysiology mediated through endothelial dysfunction. Major comorbidities
      include diabetes, hypertension, hyperlipidemia and heart disease. Any
      asymptomatic man who presents with ED that does not have an obvious cause (e.g.,
      trauma) should be screened for vascular disease and have blood glucose, lipids,
      and blood pressure measurements. Ideally, all patients at risk but asymptomatic
      for coronary disease should undergo an elective exercise electrocardiogram to
      facilitate risk stratification. Lifestyle intervention in ED, specifically weight
      loss and increased physical activity, particularly in patients with ED and
      concomitant cardiovascular disease, is literature-supported. CONCLUSIONS: The
      recognition of ED as a warning sign of silent vascular disease has led to the
      concept that a man with ED and no cardiac symptoms is a cardiac (or vascular)
      patient until proven otherwise. Men with ED and other cardiovascular risk factors
      (e.g., obesity, sedentary lifestyle) should be counseled in lifestyle
      modification.

PMID- 16409217
TI  - Educating physicians to treat erectile dysfunction patients: development and
      evaluation of a course on communication and management strategies.
AB  - PURPOSE: To describe the development and assess the outcome of a workshop on
      erectile dysfunction (ED) management based on participating physicians
      evaluations. METHOD: The study involved physicians who attended a workshop
      offered throughout the country, during a 3-year period. The workshop included
      tutorials, video-based dramatizations, and role-play sessions. A pilot study
      investigated the workshop's impact on physicians' attitudes toward patient
      centeredness and sexual behavior issues; Patient-Practitioner Orientation Scale
      (PPOS) and Cross Cultural Attitude Scale (CCAS) were administered before and
      after the course. New knowledge acquisition, quality of presentation, and
      workshop's usefulness in their clinical practice were the dimensions used for
      workshop's evaluation. Analysis used quantitative and qualitative methods.
      RESULTS: A total of 194 questionnaires were administered during the pilot study
      and the response rate was 53.6%. A shift in attitudes toward patient-centeredness
      and less judgmental attitude toward patients' sexual attitudes were revealed
      (total PPOS score and Sharing subscale: P < 0.05, CCAS: P < 0.001). Six hundred
      physicians were asked to evaluate the workshops and the response rate was 62.3%.
      The tutorial session for "medical treatment of ED" (P < 0.001) and the role-play
      on sexual history taking (P < 0.05) received higher evaluation scores.
      Qualitative analysis showed that the most frequently reported category referred
      to the appropriateness of role-play as a teaching and awareness-raising technique
      (31.25%); a need for changes in clinical practice and communication patterns was
      identified by 20% of the participants who stressed the necessity for
      multidisciplinary approach, as well as the adoption of a nonjudgmental attitude
      toward patients. CONCLUSION: Training courses on ED management, using a
      combination of tutorial and interactive sessions, constitute an effective way of
      providing knowledge, enhancing physicians' communication skills with ED patients,
      and influencing attitudes toward patient-centeredness in sexual issues. Such
      results strongly support the establishment of sexual medicine courses at
      continuing medical education curricula.

PMID- 16409218
TI  - On orgasm, sexual techniques, and erotic perceptions in 18- to 74-year-old
      Swedish women.
AB  - OBJECTIVES: To explore, in an age perspective, women's lifetime sexual techniques
      and the extent to which they had led to orgasm. To relate these techniques and
      current erotic perceptions to orgasmic function in women sexually active during
      the last 12 months and to describe the relative impact of orgasmic
      function/dysfunction on their sexual well-being. METHODS: A nationally
      representative sample of 18- to 74-year-old women (N = 1,335) participated.
      Nearly all were heterosexual. Current orgasmic capacity was broadly and
      subjectively classified into: no, mild, or manifest dysfunction. Sexual
      techniques and erotic perceptions were recorded together with level of sexual
      satisfaction. RESULTS: Generational differences characterized age at first orgasm
      and intercourse, types and width of sexual repertoire, and also current erotic
      perceptions, while orgasmic dysfunction and distress caused by it were less age
      dependent. Likely protectors of good orgasmic function, mainly against manifest
      dysfunction, were: a relatively early age at first orgasm, a relatively greater
      repertoire of techniques used--in particular having been caressed manually or
      orally by partner(s), achievement of orgasm by penile intravaginal movements,
      attaching importance to sexuality and being relatively easily sexually aroused.
      In turn, among other aspects of female sexual function women who did not have
      orgasmic dysfunction or distress were particularly likely to be satisfied with
      their sexual life. CONCLUSION: Besides providing data on matters frequently said
      to be sensitive this investigation shows that women's generation and with it
      several long-ranging aspects of women's sexual history and their feelings of
      being sexual are important indicators of their orgasmic and thereby their overall
      sexual well-being. When (in clinical practice) establishing treatment strategy
      for women with orgasmic dysfunction due respect should be given to these factors.

PMID- 16409220
TI  - Functional sequelae of cavernous nerve injury in the rat: is there model
      dependency.
AB  - INTRODUCTION: The rat model of cavernous nerve (CN) injury has been developed in
      an effort to define the functional and structural consequences of neural trauma
      in the corpus cavernosum. However, there is no universally accepted method of
      inducing nerve injury in this model, with neurotomy and crush models being used
      currently. To address this issue, we induced CN injury using various techniques
      in an effort to compare the hemodynamic sequelae of these injuries. METHODS:
      Twenty-five adult male Sprague-Dawley rats were divided into five groups: (1)
      control: laparotomy only; (2) exposure: laparotomy and exposure of cavernous
      nerves bilaterally without nerve manipulation; (3) neurotomy; bilateral
      neurotomy; (4) bulldog crush: bilateral nerve crush with bulldog vascular clamp;
      and (5) hemostat nerve crush: bilateral nerve crush with a hemostat. Ten days
      later, a second operation was performed during which systemic mean arterial
      pressure (MAP) and intracavernosal pressure (ICP) were measured in response to CN
      stimulation proximal to the site of injury. Hemodynamic endpoints assessed
      included ICP/MAP ratio, rate of tumescence, and rate of detumescence. RESULTS:
      The ICP/MAP ratio (mean +/- 95% confidence interval) in the control group was 70
      +/- 4%. ICP/MAP ratios were significantly reduced in all CN injury groups
      compared with control group: exposure: 41 +/- 10% (P < 0.001); neurotomy: 35 +/-
      15% (P < 0.001); bulldog crush: 39 +/- 13% (P < 0.001); hemostat crush: 31 +/- 9%
      (P < 0.0001). No significant difference existed in ICP/MAP ratios between the
      injury groups. Of note, the exposure group also demonstrated significant
      functional alterations. The rates of tumescence and detumescence were
      significantly reduced in all groups compared with the control group. CONCLUSION:
      No significant difference in the magnitude and consistency of hemodynamic
      alterations has been demonstrated in all CN injury models assessed in this study.

PMID- 16409219
TI  - Polymorphism of endothelial nitric oxide synthase gene in patients with erectile
      dysfunction.
AB  - INTRODUCTION: Endothelial-derived nitric oxide (NO), which is produced by
      endothelial nitric oxide synthase (eNOS) in response to increased blood flow,
      maintains the tumescence phase of erection. The eNOS gene is located on the
      seventh somatic chromosome and the polymorphism of this gene has been reported to
      cause changes in the structure of enzyme system, resulting in disturbance of its
      activity. AIM: The aim of this prospective study is to evaluate the relationship
      between polymorphism of eNOS gene and erectile dysfunction (ED). METHODS: Thirty
      patients with ED (mean age: 58.7 +/- 9.97, range: 39-74 years) and 25 voluntary
      controls (mean age: 56.44 +/- 7.58, range: 47-72 years) were enrolled to the
      study. Patients with ED were evaluated with International Index of Erectile
      Function (IIEF) questionnaire, routine blood tests for systemic vascular risk
      factors, and color Doppler ultrasonography while potency of the control group
      were only assessed with IIEF questionnaire. The presence of polymorphism of eNOS
      gene was determined in both groups by polymerase chain reaction in the fourth
      intron of the seventh somatic chromosome that encodes eNOS gene. RESULTS: The
      incidences of diabetes mellitus and coronary artery disease were statistically
      higher in the ED group (P = 0.023 and 0.029, respectively) while mean IIEF score
      was significantly lower (P = 0.001). Evaluation with color Doppler
      ultrasonography revealed penile arterial insufficiency in six cases, cavernosal
      insufficiency in 19 cases, and mixed vascular insufficiency in five cases. The
      distributions of three eNOS genotypes (eNOS4b/b, eNOS4a/b, and eNOS4a/a) among ED
      patients and controls were similar (P > 0.05). However, eNOS4a/b genotype was
      statistically higher in diabetics (P = 0.042). Also, 80% of the patients with
      severe ED and 54.5% of the diabetic patients with ED had eNOS4a/b genotype.
      CONCLUSION: In our study, no correlation was detected between the polymorphism of
      eNOS gene and ED. However, 80% of the patients with severe ED and 54.5% of the
      diabetic patients with ED had eNOS4a/b genotype. Based on our data, it seems that
      diabetic patients with ED tend to have more eNOS4a/b genotype.

PMID- 16409221
TI  - Phosphodiesterase type 5 is not upregulated by tadalafil in cultures of human
      penile cells.
AB  - OBJECTIVE: Tadalafil, a long-acting phosphodiesterase type 5 (PDE5) inhibitor,
      improves the erectile response by inhibiting cyclic guanosine monophosphate
      (cGMP) breakdown. Sustained higher levels of cGMP may hypothetically upregulate
      PDE5 expression and/or activity and lead to tachyphylaxis. We have investigated
      whether PDE5 upregulation occurs in vitro in cultures of human penile cells
      subjected to long-term incubation with increasing concentrations of tadalafil in
      the presence of a nitric oxide (NO) donor. METHODS: Human corpora cavernosa
      smooth muscle cells (CSMC) and tunica albuginea fibroblasts (TAF) primary
      cultures were characterized by immunocytochemistry and Western blot, and
      incubated with graded concentrations of tadalafil for 14 days, adding S-nitroso-N
      acetyl penicillamine (SNAP) as an NO donor for the last 24 hours or at time zero,
      and cGMP levels were measured. Incubations were repeated for 7, 10, and 14 days,
      in the presence of SNAP, and PDE5 was estimated by Western blot, and at 14 days,
      by immunocytochemistry combined with quantitative image analysis, and by real
      time reverse transcriptase polymerase chain reaction (RT-PCR). Constructs of the
      human PDE5A promoter expressing luciferase were cloned and transfected into CSMC,
      and promoter activation by 8-deoxybromo-cGMP (8-Br-cGMP) was measured by
      luminometry. RESULTS: Incubations of CSMC with SNAP and tadalafil up to 14 days
      did not upregulate PDE5 mRNA or protein levels. With TAF, PDE5 protein was also
      not upregulated despite a slight increase in mRNA levels. PDE5 enzyme activity
      was unaffected by tadalafil in either CSMC or TAF. No upregulation of the PDE5
      promoter was observed with up to 2 mM 8-Br-cGMP. CONCLUSIONS: Long-term
      incubation of human penile cells with tadalafil at concentrations above the in
      vitro IC50, and around the in vivo Cmax utilized in the clinical setting, did not
      upregulate PDE5A expression nor decrease cGMP levels. These data suggest that
      PDE5 upregulation is unlikely to occur in vivo on long-term tadalafil treatment.

PMID- 16409222
TI  - A new evaluation concept and its measurement: "male sexual anticipating
      cognitions".
AB  - CONTEXT: The development of sex-active drugs justifies the use of scales for
      evaluating changes induced by such forms of therapy. Among the tools available
      for evaluating erectile dysfunction (ED), the International Index of Erectile
      Function is the most widely used. Analysis of the scientific literature shows
      that these instruments remain primarily focused on functional aspects of ED. The
      vulnerability factors involved in ED are mainly based upon organic
      characteristics, e.g., age, cardiovascular diseases, or diabetes, but the
      psychological factors involved in the occurrence and maintenance of ED are less
      studied. OBJECTIVE: This conclusion led us to develop a French self-administered
      instrument, based on patients' subjective sexual experiences, to evaluate "male
      sexual anticipating cognitions," using Apter's reversal theory as a framework.
      DESIGN, SETTING, AND PATIENTS: We present here the first stages of the
      development of this new instrument. We carried out semistructured, one-to-one
      interviews with patients with psychogenic ED and patients with mixed ED. Eighteen
      one-to-one interviews were held in several urologic/andrologic and psychiatric
      sexologist services. Interviews were continued until the required information was
      obtained. Analyses of the content were performed to generate items for the new
      instrument. RESULTS: Dimensions isolated were those of (a) sexual beliefs; (b)
      metamotivational modes; and (c) dysfunctional coping. Pools of items are
      currently being analyzed by 108 experts (psychologists, sexologists,
      andrologists, urologists) to determine if additional items are required. The
      acceptability and the comprehensiveness of this preliminary questionnaire will be
      tested by 320 patients in a multicentric study, to produce a shorter
      questionnaire featuring the most relevant items. Once validated, this
      multidimensional instrument could be used to assess treatment efficacy of the
      mixed and psychogenic components of ED.

PMID- 16409223
TI  - Impact of oral contraceptives on sex hormone-binding globulin and androgen
      levels: a retrospective study in women with sexual dysfunction.
AB  - INTRODUCTION: Oral contraceptives (OCs) have been the preferred method of birth
      control because of their high rate of effectiveness. OC use, however, has been
      associated with women's sexual health complaints and androgen insufficiency. OC
      use is associated with a decrease of androgen ovarian synthesis and an increase
      in the production of sex hormone-binding globulin (SHBG). There have been limited
      studies assessing SHBG values after discontinuation of OC use. AIM: To
      retrospectively investigate SHBG levels before and after discontinuation of OC
      use. MAIN OUTCOME MEASURE: Sex hormone-binding globulin values were compared at
      baseline, while on the OC, and well beyond the 7-day half-life of SHBG at 49-120
      (mean 80) days and >120 (mean 196) days after discontinuation of OCs. METHODS: A
      total of 124 premenopausal women with sexual health complaints for >6 months met
      inclusion/exclusion criteria. Three groups of women were defined: (i) "Continued
      Users" (N = 62; mean age 32 years) had been on OCs for >6 months and continued
      taking them; (ii) "Discontinued-Users" (N = 39; mean age 33 years) had been on
      OCs for >6 months and discontinued them; and (iii) "Never-Users" (N = 23; mean
      age 36 years) had never taken OCs. RESULTS: Sex hormone-binding globulin values
      in the "Continued-Users" were four times higher than those in the "Never-User"
      group (mean 157 +/- 13 nmol/L vs. 41 +/- 4 nmol/L; P < 0.0001). Despite a
      decrease in SHBG values after discontinuation of OC use, SHBG levels in
      "Discontinued-Users" remained elevated in comparison with "Never-Users" (N = 26;
      P < 0.0001 for >120 days). CONCLUSION: In women with sexual dysfunction, SHBG
      changes in "Discontinued-Users" did not decrease to values consistent with "Never
      Users." Long-term sexual, metabolic, and mental health consequences might result
      as a consequence of chronic SHBG elevation. Does prolonged exposure to the
      synthetic estrogens of OCs induce gene imprinting and increased gene expression
      of SHBG in the liver in some women? Prospective research is needed.

PMID- 16409224
TI  - Dyspareunia and urinary sensory symptoms in India: population-based study.
AB  - INTRODUCTION: Population level estimates of sexual dysfunction in less developed
      settings where sexuality is not openly discussed or is culturally constrained are
      lacking. AIM: To determine the prevalence of dyspareunia and identify associated
      symptoms and sociocultural factors. METHODS: Data from a population-based
      national level family health sample survey conducted in Indian states from 1998
      to 1999 which collected sexual and reproductive health information from 84,644
      currently married women. The main outcome measure was dyspareunia. RESULTS: The
      overall prevalence of dyspareunia was 12.6%, with a higher prevalence in the
      central region, among newly married and younger women, among Muslims, rural
      residents, and among nonusers or traditional contraceptive method users.
      Dyspareunia was significantly more common among respondents who had urinary
      sensory symptoms when compared with their counterparts (adjusted odds ratio:
      6.57, 95% confidence interval: 6.28, 6.87). CONCLUSION: Dyspareunia prevalence
      and the associated symptoms reported in this analysis could be underestimates
      because of possible underreporting. There is a substantial hidden burden of
      sexual health problems especially affecting younger women.

PMID- 16409225
TI  - Sexual behaviors and mental perception, satisfaction and expectations of sex life
      in men and women in France.
AB  - AIM: To analyze behaviors, mental perception, satisfaction, and expectations
      relating to sexuality in France. METHODS: A total of 1,002 subjects (483 men and
      519 women) aged 35 years and over in a representative sample of the French
      population were surveyed by phone using a dedicated questionnaire in November
      2003. MAIN OUTCOME MEASURES: Sexual behaviors and mental perception, satisfaction
      and expectations concerning sexual life. RESULTS: Of the population, 80.2%
      reported having a sexual partner. The mean number of times subjects had sex per
      week was 1.8 (2.0 in men, 1.6 in women). The decision preceded the act by a few
      seconds or minutes in 82.7% of subjects. Thinking about sex was "frequent" in
      47.1% of subjects, especially for men (60.8%). Regardless of gender, sexuality
      was more synonymous with pleasure (44.0%) and love (42.1%) than with procreation,
      children, or motherhood (7.8%). During sexual intercourse, simultaneous orgasms
      and feelings of closeness were important for the majority of subjects, 35.8%
      (41.6% of men) and 22.8%, respectively; foreplay, enjoyment, and vaginal
      penetration were the most important accomplishments for 13.1%. Regardless of
      gender, 83.0% of subjects expressed relative or full satisfaction with their sex
      life. However, only 38.7% of subjects (31.6% of men and 45.2% of women) did not
      wish to change anything, while 17.2% would like to have more time for it. Of the
      subjects, 63.0% reported a decrease in sexual desire during periods of work
      related stress, especially in women (72.3%). The main sexual complaints reported
      by men were diminution of sexual desire (24.9%), early ejaculation (23.7%), and
      erectile problems (14.4%). In women, they were diminution of sexual desire
      (45.7%), orgasm disorders (15.5%), and dyspareunia (15.5%). CONCLUSIONS: This
      survey showed that the attitude of subjects, especially men, toward sexuality is
      changing through years and highlighted the extent of sexual problems in the
      general population.

PMID- 16409226
TI  - Five years after the launch of Viagra in Korea: changes in perceptions of
      erectile dysfunction treatment by physicians, patients, and the patients'
      spouses.
AB  - INTRODUCTION: When Viagra was first launched in Korea in 1999, there were high
      expectations for its efficacy, and strong concerns regarding its safety and
      potential for misuse. PURPOSE: To research changes in perceptions of erectile
      dysfunction (ED) treatment 5 years after Viagra was launched. MATERIALS AND
      METHODS: Participants in the study were drawn from six provinces in Korea. They
      were 120 physicians, 80 patients with ED who had been treated with Viagra, and 40
      women who knew that their husbands were being treated with Viagra. The study was
      conducted using a random face-to-face interview and a questionnaire. RESULTS:
      Most physicians responded that since the launch of Viagra, discussions on the
      topic of sex are more acceptable (92%), and the number of patients seeking
      medical treatment for ED has increased (92%). They now have a better
      understanding of ED (98%). They are more confident of treatment (96%), more
      interested in identifying ED patients (72%), and more comfortable at initiating
      discussions on ED with patients (80%). Prior to the launch of Viagra, 65% of
      internal medicine/family medicine doctors did not prescribe any special treatment
      for ED. However, after Viagra became available, 92% of these doctors prescribed
      oral medication for ED, thus confirming their position as primary physicians for
      ED treatment. One of the most distinct changes in perceptions related to Viagra
      is the higher level of confidence shown by physicians, patients, and patients'
      spouses in the safety of the drug. CONCLUSION: Five years after the launch of
      Viagra, the social environment has changed, making discussions of sex more
      acceptable. A larger number of patients now seek medical treatment for ED, and
      there is an increased acknowledgment for ED treatment by physicians, patients,
      and patients' spouses. Moreover, these parties are now more confident about the
      safety of Viagra.

PMID- 16409227
TI  - Peak systolic velocities may be falsely low in young patients with erectile
      dysfunction.
AB  - INTRODUCTION: Introduction of duplex ultrasonography with color flow Doppler
      analysis after intracavernous injection of vasoactive drugs has been reported to
      be a minimally invasive and accurate method, and considered the gold-standard
      technique for evaluating penile hemodynamics. However, several studies have
      demonstrated that in some cases Color Doppler Ultrasound (CDU) testing may result
      in wrong diagnosis because of anxiety and increased sympathetic stimulation. AIM:
      This study was carried out to evaluate the impact of age on the decision to
      repeat CDU in patients with initial low peak systolic velocities (PSVs). METHODS:
      This is a prospective study involving 71 patients with erectile dysfunction (ED)
      who presented to the Department of Andrology, Sexology and Sexually Transmitted
      Diseases at Cairo University between December 2000 and April 2002. An
      intracavernous pharmacotest and CDU with prostaglandin E1, papaverine, and
      phentolamine was performed. All patients in the study had poor response to
      intracavernous pharmacotesting and achieved a low PSV (<30 cm/second) during the
      initial CDU examination. The CDU was repeated 2 weeks later. The 71 patients were
      grouped into four according to age: group A (20-29 years old) consisted of 11
      patients, group B (30-39 years old) consisted of 19 patients, group C (40-49
      years old) consisted of 20 patients, and group D (50-59 years old) consisted of
      21 patients. RESULTS: The group A patients experienced a statistically
      significant increase (P < 0.05) in their PSV measurements, which reached normal
      values in the second CDU. None of the patients of groups B, C, or D experienced
      any statistically significant change (P > 0.05) in their PSV measurements in the
      second CDU, which remained below normal values. Also, there was a statistically
      significant difference between the PSV measurements of group A and the other
      three groups. CONCLUSIONS: Low PSV measurements in young men (less than 30 years
      old) with ED should be interpreted with caution. The effect of sympathetic
      overtone because of the environment in the office and anxiety related to penile
      injection, together with any underlying psychological disturbance, should be
      taken into consideration during the evaluation of the results of the CDU.
      Repetition of the CDU is recommended before considering any additional invasive
      diagnostic or therapeutic modalities.

PMID- 16409228
TI  - Lower urinary tract symptoms in patients with erectile dysfunction: analysis of
      risk factors.
AB  - INTRODUCTION: The association between erectile dysfunction (ED) and lower urinary
      tract symptoms (LUTS) is unclear. Conventionally, little attention has been given
      to the association between ED and LUTS. AIM: To evaluate ED risk factors in
      patients with LUTS. METHODS: A total of 476 male patients with ED were enrolled
      in this study. They were interviewed for ED by using the International Index of
      Erectile Function. All patients were screened for socio-demographic data and risk
      factors for ED that included age, smoking, diabetes, hypertension, ischemic heart
      disease (IHD), dyslipidemia, and psychological disorders. All patients were also
      screened for LUTS by using the International Prostate Symptoms Score. Patients
      underwent routine laboratory investigation in addition to testosterone and
      prolactin assessment. RESULTS: Mean age +/- SD were 55.1 +/- 8.7 years and 40.4
      +/- 11.2 years for patients with and without LUTS, respectively. Of the patients,
      27.6% had mild, 30% had moderate, and 42.4% had severe ED. Seventy-seven percent
      of the patients had LUTS; of those, 22.8% had mild, 42% had moderate, and 35.2%
      had severe grades. Significant associations between LUTS and both the longer
      duration and the increased severity of ED were detected. There were also
      significant associations between LUTS and the following ED risk factors: age,
      obesity, diabetes, hypertension, and IHD. Presence of at least one risk factor
      was significantly associated with LUTS in patients with ED. CONCLUSIONS: ED risk
      factors are very prevalent among patients with LUTS. The current study supports
      previous studies suggesting that LUTS were significantly associated with ED.
      Furthermore, a significant association between the increased severity of LUTS and
      the increased severity of ED was confirmed.

PMID- 16409229
TI  - Chronic prostatitis in premature ejaculation: a cohort study in 153 men.
AB  - INTRODUCTION: Premature ejaculation is a common male sexual dysfunction,
      affecting 30-40% of sexually active men in an age-dependent manner. Chronic
      prostatitis has been suggested as an important organic cause of premature
      ejaculation. AIM: The aim of this study was to confirm previous data reported on
      the incidence of chronic prostatitis in a large cohort of patients with primary
      and secondary premature ejaculation. METHODS: A total of 153 consecutive
      heterosexual men aged 29-51 years with premature ejaculation and another 100 male
      healthy subjects were included in this study. Sequential microbiologic specimens
      were obtained according to the standardized Meares and Stamey protocol.
      Nonbacterial prostatitis was defined by the evidence of prostatic inflammation
      but negative cultures of urine and prostatic fluids in men with various
      genitourinary symptoms. RESULTS: There was no significant difference between
      patients and control subjects regarding age, education, or intercourse frequency.
      Prostatic inflammation was found in 64% and chronic bacterial prostatitis in 52%
      of the patients with premature ejaculation, respectively, showing statistical
      significance compared with control subjects (P < 0.05). CONCLUSIONS: Results in
      our study showed a high prevalence of chronic prostatitis in patients with
      premature ejaculation. Examination of the prostate, physically and
      microbiologically, should be considered during assessment of patients with
      premature ejaculation.

PMID- 16409230
TI  - Minimizing the losses in penile lengthening: "V-Y half-skin half-fat advancement
      flap" and "T-closure" combined with severing the suspensory ligament.
AB  - INTRODUCTION: The technique most commonly used for penile lengthening is the
      release of the suspensory ligament in combination with an inverted V-Y skin
      plasty. This technique has drawbacks such as the possibility of reattachment of
      the penis to the pubis, a hump that forms at the base of the penis, in addition
      to alteration in the angle of erection. AIM: In this work, we describe a new
      technique that overrides these drawbacks and minimize the loss of gained length.
      METHODS: The suspensory ligament was released through a penopubic incision. The
      caudal flap of the resected ligaments was reflected caudally and sutured to the
      Buck's fascia. The V flap was incised. The caudal half of the V was deskinned,
      leaving a cranial skin-covered V flap, and a caudal, rectangular fat flap. The
      fat flap was pulled into the gap between the base of the penis and the pubis and
      secured in position by suturing its deep surface and lower edge to the pubis.
      This maneuver filled up the gap. The V incision was closed as a Y. The penopubic
      incision was closed as a T shape, to avoid pulling the penis back at skin
      closure. A stay suture stretched from the glans to the thigh, maintaining the
      penis in the stretched position. A urinary catheter was inserted. RESULTS: Six
      months after surgery, there was no loss in the length gained. The angle of
      erection (as reported by the patient) was similar to that prior to the procedure.
      The skin incisions left no hump and a faint scar that was not troublesome to the
      patient. CONCLUSION: "V-Y half-skin half-fat advancement flap" and "T-closure"
      may improve the results of suspensory ligament release for penile lengthening.
      The reported techniques minimize the losses compromising length gain, whether in
      surgery or following it.

PMID- 16409231
TI  - Satyriasis: the antiquity term for vulvodynia?
AB  - From ancient times, through the Middle Ages, and well into the 19th century,
      physicians concentrated on catastrophic medical conditions and illnesses rather
      than on quality of life issues. Wars, plagues, and pestilence left little time,
      energy, or concern for "discomfort" problems. Therefore, it is not surprising
      that women's conditions that caused distressing symptoms but fell short of major
      morbidity and mortality were not given a prominent position in medicine until
      relatively recently. This is especially the case with vulvodynia, a condition
      that has been reported to affect approximately 15% (and in some studies up to
      27%) of the female population at some point in their lives. Despite its high
      prevalence, this condition was not discussed or reported in traditional medical
      textbooks until the end of the 1800s. Now, we propose another viewpoint on when
      the first description of vulvodynia appeared; that is, that vulvodynia was
      described as far back as the 1st century CE. From our review of the ancient
      medical literature, we believe that the condition described by Soranus as
      "satyriasis in females" was actually vulvodynia.

PMID- 16409232
TI  - Penile girth augmentation using flaps "Shaeer's augmentation phalloplasty": a
      case report.
AB  - INTRODUCTION: Current girth augmentation techniques rely either on
      liposuction/injection or on the use of dermal fat grafts. These procedures have
      serious disadvantages, including regression in gained size, deformities,
      irregular contour, and asymmetry. Ideally, the augmentation technique should
      ensure durability and symmetry. This case report describes the first application
      of a flap (superficial circumflex iliac artery island flap) in penile girth
      augmentation. MATERIALS AND METHODS: The superficial circumflex iliac vessels
      were identified and the groin flap was elevated from lateral to medial, rotated
      toward the penis, and tunneled into a penopubic incision. It was wrapped around
      the penis short of the corpus spongiosum and insinuated under the glans. RESULTS:
      Six months after surgery, the patient had an erect girth of 19.5 cm and a flaccid
      girth of 16.5 cm, compared with 11 cm and 7 cm, respectively, before surgery,
      thus maintaining the intraoperative girth gain. The outer surface felt smooth
      with no lobulation. The size of the glans was proportionate to the shaft's girth.
      CONCLUSION: This case report shows that the application of flaps in penile girth
      augmentation may provide a reliable alternative to the currently applied
      techniques. Glans flaring promotes the aesthetic results and is applicable with
      other techniques of penile girth augmentation.

PMID- 16409233
TI  - Paraffinoma and ulcer of the external genitalia after self-injection of vaseline.
AB  - We present a 42-year-old circumcised man with a 10-cm firm, irregular penile mass
      associated with multiple penile ulcers, voiding difficulty, and erectile
      dysfunction. He reluctantly admitted that 8 months previously, he had multiple
      mineral-oil (vaseline) self-injections to the penis, for penile enlargement
      purposes. Histopathological examination revealed the condition was consistent
      with mineral-oil granuloma (paraffinoma). The patient did not accept surgical
      intervention; therefore, we performed local therapy (intralesional triamcinolone)
      and hot-water baths. Paraffinoma results from mineral-oil injections. Such
      injections are rare; however, they are still being performed in some countries in
      Eastern Europe and the Far East such as Korea. Increased physician and public
      awareness are needed for prevention and treatment of complications of this
      physically and psychologically debilitating and destructive problem.

PMID- 16409235
TI  - Crural perforation during penile prosthetic surgery.

PMID- 16409234
TI  - Case report: Avoidance of palpable corporal fibrosis due to priapism with
      upregulators of nitric oxide.
AB  - INTRODUCTION: Recent evidence suggests that blocking inducible nitric oxide (NO)
      synthase in the penis may exacerbate fibrotic processes and that application of
      medications known to increase NO in tissues may prevent fibrosis. AIM: To report
      the use of an antifibrotic regimen consisting of medications known to upregulate
      NO production in two patients with refractory priapism. METHODS: Two patients
      presented with priapism of greater than 48-hour duration. After corporal
      aspiration/irrigation and shunting procedures failed, both were prescribed a
      daily antifibrotic regimen comprising the phosphodiesterase inhibitors
      pentoxifylline and sildenafil, and the NO precursor, L-arginine. RESULTS: At 1
      year, both patients were found to have supple corpora without evidence of
      corporal fibrosis. CONCLUSIONS: An antifibrotic regimen consisting of
      upregulators of NO production may ameliorate the corporal fibrosis associated
      with recalcitrant priapism.

PMID- 16409236
TI  - Combination pharmacotherapy in the management of patients with hard-to-treat
      erectile dysfunction.

PMID- 16409238
TI  - Constant rate infusion for topical ocular delivery in horses: a pilot study.
AB  - OBJECTIVE: To assess the efficacy and kinetics of a continuous infusion modality
      for topical ophthalmic drug delivery via subpalpebral lavage in horses. ANIMALS
      STUDIED: Five ophthalmically normal horses PROCEDURES: A constant-rate continuous
      delivery pump was used to apply 0.01% fluorescein solution to the eyes of five
      ophthalmically normal horses via subpalpebral lavage. Fluorescein was applied at
      a rate of 0.14 mL/h for 72 h. Tear samples were collected from the ventral
      conjunctival fornix at regular intervals via capillary tube and tear fluorescein
      concentrations were determined via spectral assay. Laboratory studies to evaluate
      the procedures used in the study also were performed. RESULTS: Overall mean tear
      film fluorescein concentration was approximately 20% of the applied concentration
      of fluorescein. However, tear film fluorescein concentrations varied considerably
      between horses and over time. Dilution varied from 0.62% to 60% of the applied
      concentration. Air pockets sporadically appeared in subpalpebral lavage tubing
      lines, resulting in discontinuous topical application of fluorescein.
      CONCLUSIONS: Constant-rate delivery of ophthalmic medications using a continuous
      infusion pump may provide a valuable method of topical drug delivery if tear film
      dilution of drugs is taken into account.

PMID- 16409240
TI  - Comparison of the rebound tonometer (ICare) to the applanation tonometer (Tonopen
      XL) in normotensive dogs.
AB  - OBJECTIVE: To compare intraocular pressure (IOP) measurements obtained by
      recently introduced rebound tonometer (ICare) and the well-known applanation
      tonometer Tonopen XL in normal canine eyes. METHODS: In a prospective,
      randomized, single-center study, IOP measurements by ICare and Tonopen XL
      tonometers were compared in 160 nonpathologic canine eyes (80 dogs). Complete
      slit-lamp biomicroscopy and indirect ophthalmoscopy were performed on each dog.
      Rebound tonometry was performed first and immediately after topical anesthetic
      drops were instilled in both eyes. One minute after the application of the
      topical anesthetic, applanation tonometry was performed in both eyes. The
      intraocular pressures obtained by use of both techniques were compared by
      statistical analysis. RESULTS: The mean IOP readings were 9.158 mmHg (SD 3.471
      mmHg) for the ICare tonometer (x) and 11.053 mmHg (SD 3.451 mmHg) for the Tonopen
      XL readings (y). The mean difference in intraocular pressures (-1.905 mmHg) was
      within clinically acceptable limits. The correlation coefficient (r2) of the
      relationship within both tonometers was r2=0.7477. The corresponding linear
      regression between the tonometers readings was y=0.6662x+4.942. CONCLUSIONS:
      Intraocular pressures obtained with the ICare rebound tonometer were concordant
      with the IOP readings obtained by applanation Tonopen XL, but ICare values were
      significantly (P<0.0001) lower. Rebound tonometry could be an appropriate
      tonometry method for routine clinical use after its calibration for canine eyes.

PMID- 16409239
TI  - Comparative fluorescein angiography of the normal sheep and goat ocular fundi.
AB  - Fluorescein angiography without sedative or anesthetic agents was evaluated in 20
      normal goats and 20 normal sheep. All of the angiographic phases were observed
      using 20 mg/kg fluorescein IV in both species. Fundus fluorescein angiography
      results revealed wide stars of Winslow in the tapetal fundus, central or marginal
      flow during the first part of the arterial phase, delayed filling of the focal
      areas in the choroid near the optic disc that often coincided with others in the
      disc, and lack of evidence of the 'striate area' in the tapetal fundi. In goats,
      the angiographic times were 6.54+/-1.25 s for the arterial phase (TA), 7.80+/
      1.37 s for the arterio-venous phase (TAV), and 14.13+/-2.01 s for the venous
      phase (TV). I1: 1.30+/-0.30 s (time elapsing between TA and TAV), and I2: 6.20+/
      1.60 s (time elapsing between TAV and TV). In sheep, times were 9.54+/-2.18 s TA,
      11.73+/-2.10 s TAV, and 20.86+/-2.74 s TV. I1: 2.04+/-0.75 s and I2: 8.98+/-2.47
      s, respectively. Due to the large size of the fundic vessels in sheep and goats,
      fluorescein angiography of the retinal vasculature can facilitate the study of
      the different vascular diseases in these species.

PMID- 16409241
TI  - Effect of lacrimal punctal occlusion on tear production and tear fluorescein
      dilution in normal dogs.
AB  - OBJECTIVE: To evaluate effects of lacrimal punctal plugs positioned in either the
      upper, lower, or combination of upper and lower lacrimal canaliculi on plug
      retention and tolerance; tear production, as measured by the Schirmer tear test;
      and the dilution of fluorescein within the tear film in normal dogs. MATERIAL AND
      METHODS: Lacrimal punctal plugs were positioned in the lower, upper, or
      combination of lower and upper plugs in six laboratory-quality Beagles under
      topical anesthesia. Retention of plugs was evaluated daily from 8 to 23 days by
      visual inspection and slit-lamp biomicroscopy. Schirmer tear tests (STT 1 without
      topical anesthesia) were performed at 48-h intervals. Dilution of fluorescein was
      determined at 5- and 45-min post-fluorescein instillations once weekly. RESULTS:
      Lacrimal punctal plugs of 0.4 and 0.6 mm in diameter were retained for 14 (lower
      plugs: 100%) and 23 days (75%), and for the upper plugs at 8 days less often
      (75%), and were infrequently locally nonirritating. Combination of lower and
      upper plugs seemed to adversely affect retention of either plug. When loss of the
      plugs occurred, a next larger size plug was necessary suggesting some stretching
      of the lacrimal canaliculi occurred. Pre- and postplug placement STT results
      indicated no change with lower and combination lacrimal punctal plugs, but
      decreased levels following upper lacrimal punctal plugs. Tear fluorescein levels
      at 5 and 45 min in control eye (no punctum plugs) were 3.39% and 0.14%,
      respectively. With lower, upper, and the combination of lower and upper lacrimal
      puncta plugs, tear fluorescein levels at 45 min were higher than the controls
      (lower: 0.76%; upper: 0.45%, and combination 0.56%). CONCLUSION: Lacrimal punctal
      silicone plugs are retained for 8-23 days in the lower, upper, and combined lower
      and upper canaliculi at high rates. Effects on STT levels appear limited.
      Fluorescein within the tear film persists longer with all different positioned
      lacrimal punctum plugs than in the control eyes.

PMID- 16409242
TI  - Suspected ivermectin toxicosis in a miniature mule foal causing blindness.
AB  - A 9-week-old miniature mule foal presented to the Veterinary Medical Teaching
      Hospital for acute blindness, ataxia, and depression following an overdose of an
      over-the-counter ivermectin-based de-worming medication. Ophthalmic examination
      and electrodiagnostic evaluation eliminated outer retinal abnormalities as the
      primary cause of the bilateral blindness, implicating instead a central
      neurologic effect of the drug. With symptomatic and supportive care, the foal
      recovered fully and regained its vision.

PMID- 16409243
TI  - Effects of medetomidine and medetomidine-butorphanol combination on Schirmer tear
      test 1 readings in dogs.
AB  - Medetomidine is a commonly used sedative in veterinary medicine whether
      administered alone or in combination with an opioid such as butorphanol. There
      are no previous studies that look at the effects of this drug on sequential
      Schirmer tear test (STT) 1 readings in dogs, including effects on tear production
      after reversal of the drug. The present study looked at two groups of 10 dogs
      each that were sedated with intravenous medetomidine or a combination of
      medetomidine and butorphanol. All dogs had tear readings taken presedation, 15
      min postsedation, and 15 min after reversal of medetomidine with atipamezole.
      Results revealed that intravenous sedation with medetomidine and medetomidine
      butorphanol in dogs with no history of ophthalmic disease and presedation STT 1
      readings above 15 mm/min, causes a significant decrease in tear production that
      is measurable at 15 min postsedation. Readings returned to near presedation
      values within 15 min postreversal in most cases. It is therefore recommended that
      all eyes be treated with a tear substitute from the time the sedative is given
      until at least 15 min after reversal.

PMID- 16409244
TI  - Ocular effects of topical 0.03% bimatoprost solution in normotensive feline eyes.
AB  - OBJECTIVE: The current study was undertaken to evaluate the effects of topically
      applied bimatoprost, an ocular hypotensive lipid, on intraocular pressure (IOP)
      and pupil size (PS) in healthy cats. ANIMAL STUDIED: Nine European Shorthair cats
      free from clinically relevant ocular abnormalities were used in the study.
      PROCEDURES: Pretreatment baseline measurements of IOP and PS were obtained
      bilaterally at 8 am, 2 pm, and 8 pm for five consecutive days (days 1 to 5). Then
      the cats received one drop twice daily (10 am and 6 pm) of bimatoprost ophthalmic
      solution 0.03% (Lumigantrade mark, Allergan Inc., Irvine, CA USA), in one
      randomly selected eye and one drop of artificial tears in the fellow eye (control
      eye) for 5 days (days 6 to 10). Values for IOP and PS were obtained under the
      same conditions as in the pretreatment phase. The potential for ocular irritation
      following bimatoprost application was also evaluated. RESULTS: During the
      pretreatment period, the mean IOP and mean PS were not significantly different
      between the eyes subsequently treated with bimatoprost and those subsequently
      determined as controls. During the treatment period, the mean IOP in bimatoprost
      treated eyes was not significantly lower than in control eyes (14.2+/-2.3 vs.
      14.5+/-2.8 mmHg). Mean IOP in control eyes was not significantly changed at any
      time during the study period. A marked reduction of PS was seen in all
      bimatoprost-treated eyes, but no other clinically relevant side effects were
      observed. CONCLUSION: Twice daily topical applications of bimatoprost produced
      miosis but had no significant effect on IOP in healthy cats.

PMID- 16409245
TI  - Idiopathic sclerosing orbital pseudotumor in seven cats.
AB  - OBJECTIVE: To review the clinical presentation and histopathologic findings on a
      series of cats with orbital fibrotic disease and compare the data to that of
      humans with sclerosing orbital pseudotumor. ANIMALS: A retrospective study was
      undertaken, which identified tissue samples from seven cats between 1997 and 2002
      with a history of orbital mass effect and pathology characterized by fibrous
      tissue proliferation. PROCEDURE: Information was obtained from medical records
      for affected cats, including age, sex, clinical signs, management, and outcome,
      with histopathology re-examined. RESULTS: Six of seven cats presented with
      unilateral orbital involvement that progressed to bilateral orbital disease
      despite treatment. Onset was insidious, evolving over weeks to months and was
      associated with fixation of orbital structures. Owners of six of the cats opted
      for euthanasia because of disease progression and pain. Histopathology of
      affected orbital tissue included extensive fibrosis with encapsulation of normal
      tissues without characteristics of neoplasia. CONCLUSIONS: Clinical findings and
      histopathology of globes and orbital tissues in cats bore many similarities to
      idiopathic sclerosing orbital pseudotumor in humans. In cats, the prognosis for
      the globe appears to be poor but an elucidation of the pathogenesis and earlier
      diagnosis coupled with more aggressive treatment modalities as indicated in
      humans may be beneficial.

PMID- 16409246
TI  - Effect of age, gender, weight, and time of day on tear production in normal dogs.
AB  - OBJECTIVE: To investigate the effects of age, weight, gender, and of time of day
      on tear production in normal dogs. ANIMALS: studied One hundred
      ophthalmoscopically and systemically unremarkable dogs. PROCEDURE: Schirmer tear
      tests (STT) were performed every 2 h during the day on one randomly chosen eye of
      each of 100 dogs. RESULTS: There was a statistically significant effect of time
      of day and age on the STT measurement. The mean STT decreased by 0.4 mm for every
      1 year that age increased (P=0.007). Mean STT values taken at 10:00 am were 0.7
      mm lower than values taken at 4:00 pm (P=0.04). CONCLUSIONS: Tear production
      decreases with age in the normal dog. In this population of dogs the largest
      difference was between the 10:00 am and the 4:00 pm STT measurements, but this
      still only amounted to 0.7 mm. This value is unlikely to be of clinical
      significance in the diagnosis of keratoconjunctivitis sicca (KCS).

PMID- 16409247
TI  - Encephalitozoon hellem infection as the cause of a unilateral chronic
      keratoconjunctivitis in an umbrella cockatoo (Cacatua alba).
AB  - An umbrella cockatoo (Cacatua alba) was presented with a keratoconjunctivitis of
      9 months' duration that was refractory to antibacterial and antifungal
      treatments. Microsporidian-type spores were observed in calcofluor M2R-stained
      cytological preparations of debrided corneal epithelium. Hematoxylin and eosin
      stained sections of a conjunctival biopsy also showed a small number of
      intracellular parasites. Microsporidial DNA was detected by polymerase chain
      reaction in DNA extracted from the remaining biopsy material. Sequence analysis
      of the small subunit ribosomal RNA gene identified the microsporidium as
      Encephalitozoon hellem. The cockatoo was treated with oral albendazole for 3
      months with resolution of the signs, and then again for 4 months when the signs
      returned. Since then, the bird has remained healthy for 2 years. This is the
      second report of a microsporidial keratoconjunctivitis in a bird, and the first
      report of an E. hellem infection in a cockatoo. Ophthalmologists should consider
      E. hellem as a possible cause of a keratoconjunctivitis in parrots that is
      refractory to treatment with traditional antimicrobials.

PMID- 16409248
TI  - Surgical management of a malacic corneal ulcer in a greater one-horned Asian
      rhinoceros (Rhinoceros unicornis) using a free island tarsoconjunctival graft.
AB  - A greater one-horned Asian rhinoceros (Rhinoceros unicornis) presented for
      presumed ocular trauma to the left eye, with secondary bacterial infection,
      resulting in severe and progressive corneal ulceration. Following a poor response
      to medical therapy, the animal was anesthetized for further examination, and a
      bulbar conjunctival pedicle graft performed. This graft failed by 48-h
      postsurgery as a result of self-trauma. The animal was re-anesthetized, and a
      free island tarsoconjunctival graft performed. This second procedure was
      successful, resulting in globe preservation, cosmesis, and functional vision in
      the affected eye.

PMID- 16409249
TI  - Influence of proinflammatory cytokines on Actinobacillus actinomycetemcomitans
      specific IgG responses.
AB  - OBJECTIVE: High levels of serum anti-Actinobacillus actinomycetemcomitans
      immunoglobulin G (IgG) correlate with reduced extent and severity of periodontal
      disease and the present study was undertaken to begin testing the hypothesis that
      proinflammatory cytokines are important in the induction of optimal anti-A.
      actinomycetemcomitans IgG responses. BACKGROUND: Studies with pokeweed mitogen
      indicate that interleukin-1alpha (IL-1alpha) and IL-1beta are necessary for
      optimal IgG1 and IgG2 production and that prostaglandin E(2) (PGE(2)) and
      interferon-gamma (IFN-gamma) selectively promote IgG2, which is a major component
      of the anti-A. actinomycetemcomitans response in vivo. The pokeweed mitogen
      results suggest that these proinflammatory cytokines would also be necessary for
      optimal production of IgG specific for A. actinomycetemcomitans. METHODS:
      Peripheral blood mononuclear cells from A. actinomycetemcomitans-seropositive
      subjects with localized aggressive periodontitis were stimulated with A.
      actinomycetemcomitans in immune complexes capable of binding follicular dendritic
      cells that participate in the induction of recall responses in vivo. Cultures
      were manipulated with anti-IL-1alpha, anti-IL-1beta, anti-IFN-gamma, anti-IL-12,
      anti-CD21, indomethacin, and PGE(2). Actinobacillus actinomycetemcomitans
      specific IgG production was monitored by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Addition of follicular dendritic cells to peripheral blood
      mononuclear cells cultures resulted in follicular dendritic cell-lymphocyte
      clusters and increased anti-A. actinomycetemcomitans IgG responses (3-40-fold
      increases) compared with controls lacking follicular dendritic cells. Anti-IL
      1alpha, anti-IL-1beta, anti-IFN-gamma, anti-IL-12, anti-CD21 and indomethacin
      suppressed anti-A. actinomycetemcomitans IgG production by half or more. PGE(2)
      restored IgG responses suppressed by indomethacin. CONCLUSIONS: The cytokines IL
      1alpha, IL-1beta, IFN-gamma, IL-12, and PGE(2) were all necessary for optimal
      production of human anti-A. actinomycetemcomitans and the need for
      proinflammatory cytokines including the T helper 1 (Th1) cytokines is consistent
      with a response with a significant IgG2 component.

PMID- 16409250
TI  - Porphyromonas gingivalis heat shock protein vaccine reduces the alveolar bone
      loss induced by multiple periodontopathogenic bacteria.
AB  - OBJECTIVES: Heat shock protein (HSP) can be utilized as a vaccine to cross
      protect against multiple pathogenic species. The present study was performed to
      evaluate Porphyromonas gingivalis heat shock protein 60 (HSP60) as a vaccine
      candidate to inhibit multiple bacteria-induced alveolar bone loss. MATERIAL AND
      METHODS: Recombinant P. gingivalis HSP60 was produced and purified from P.
      gingivalis GroEL gene. Rats were immunized with P. gingivalis HSP60, and
      experimental alveolar bone loss was induced by infection with multiple
      periodontopathogenic bacteria. RESULTS: There was a very strong inverse
      relationship between postimmune anti-P. gingivalis HSP immunoglobulin G (IgG)
      levels and the amount of alveolar bone loss induced by either P. gingivalis or
      multiple bacterial infection (p=0.007). Polymerase chain reaction data indicated
      that the vaccine successfully eradicated the multiple pathogenic species.
      CONCLUSIONS: We concluded that P. gingivalis HSP60 could potentially be developed
      as a vaccine to inhibit periodontal disease induced by multiple pathogenic
      bacteria.

PMID- 16409251
TI  - Differential localization of laminin gamma and integrin beta in primary cultures
      of the rat gingival epithelium.
AB  - OBJECTIVES: The aim of this study was to investigate the differential
      immunolocalization of laminin gamma(2) and integrin beta(4) in primary cultures
      of the rat gingival epithelium. METHODS: The gingival epithelium was obtained
      from Sprague-Dawley rats and was cultured in serum-free keratinocyte growth
      medium (DK-SFM). Western blotting analysis, immunofluorescence, confocal laser
      scanning microscopy (CLSM), and immuno-gold labeling for laminin gamma(2) and
      integrin beta(4) were employed. CLSM images for laminin and integrin were
      analyzed in horizontal (x-y axis) and in vertical (x-z axis) sections. RESULTS:
      Both laminin gamma(2) and integrin beta(4) were detected by Western blot analysis
      in the gingival epithelium. Immunolocalization of laminin gamma(2) was distinct
      in the cytoplasm to form one or two irregular rings in gingival epithelial cells.
      By contrast, integrin beta(4) was localized diffusely in the cytoplasm. F-actin
      (indicating actin filaments) was clearly discernible at the periphery of the
      cytoplasm to form a cellular fringe. In x-z axis images obtained by CLSM, laminin
      gamma(2) was recognized as large foci in the most inner portion just above the
      basal plasma membrane. Integrin beta(4) existed in the area where F-actin was
      labeled surrounding the membrane. Immuno-electron microscopy showed that 10nm
      colloidal gold particles indicating laminin gamma(2) were mainly localized at the
      extracellular portion and in the peripheral cytoplasm, whereas integrin beta(4)
      was distributed in the cytoplasm close to the basal plasma membrane but not in
      extracellular regions. CONCLUSIONS: In primary cultures of the rat gingival
      epithelium, both laminin gamma(2) and integrin beta(4) may be produced by the
      epithelium, and irregular rings of laminin gamma(2) are formed in areas where
      gingival cells adhere to the extracellular matrix.

PMID- 16409253
TI  - Capsaicin-induced local elevations in collagenase-2 (matrix metalloproteinase-8)
      levels in human gingival crevice fluid.
AB  - BACKGROUND AND OBJECTIVES: Application of capsaicin on alveolar mucosa provokes
      pain and neurogenic vasodilatation in the adjacent gingiva. Pain-associated
      inflammatory reactions may initiate expression of several pro-inflammatory
      mediators. Collagenase-2 (matrix metalloproteinase-8: MMP-8) is the major
      destructive protease, especially in the periodontitis-affected gingival crevice
      fluid (GCF). With this background, we wished to study whether capsaicin
      stimulation of alveolar mucosa can induce changes in the GCF MMP-8 levels.
      MATERIAL AND METHODS: For 10 generally and periodontally healthy human
      volunteers, capsaicin (3%)-moistened filter paper was applied unilaterally to the
      buccal alveolar mucosa on the anterior maxilla. GCF samples were collected from
      the tooth at the stimulation site and from several other incisors in the upper
      jaw. MMP-8 levels and molecular forms in GCF samples were determined by
      immunofluorometric assay (IFMA) and western immunoblotting, respectively.
      RESULTS: Capsaicin stimulation of the alveolar mucosa induced significant local
      elevations in levels and activation of MMP-8 in GCF of the adjacent teeth.
      Western immunoblot revealed that both neutrophil- and mesenchymal-type MMP-8
      isoforms were elevated and activated, together with 110 kDa high-molecular size
      MMP-8 species. This capsaicin-evoked MMP-8 elevation lasted several minutes after
      stimulation. During the experiments, no marked changes occurred in MMP-8 levels
      in the GCF of distantly located teeth. CONCLUSIONS: These results suggest that
      capsaicin-evoked neurogenic gingival inflammation can trigger the expression and
      activation of MMP-8 in GCF of the adjacent teeth.

PMID- 16409252
TI  - Neonatal dexamethasone and chronic tianeptine treatment inhibit ligature-induced
      periodontitis in adult rats.
AB  - OBJECTIVE: The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis
      has been found to play a significant role for susceptibility and resistance to
      periodontal disease. In the present study we have investigated the effects of two
      different treatment strategies, which have been found to down-regulate the HPA
      axis, on ligature-induced periodontitis. METHODS: In experiment 1, newborn rats
      were treated with the synthetic glucocorticoid hormone dexamethasone-21
      phosphate, which permanently down-regulates HPA axis responsiveness. In
      experiment 2, adult rats were treated with the novel antidepressant drug
      tianeptine, which opposes the action of stress. Periodontitis was inflicted upon
      all rats. Just before decapitation the animals received gram-negative bacterial
      lipopolysaccharide (LPS) to induce a robust immune and HPA axis response.
      RESULTS: Compared to the saline-treated control rats, dexamethasone-treated rats
      had significantly less periodontal bone loss (p < 0.01), reduced expression of
      glucocorticoid receptors in the hippocampus (p < 0.001), lower corticosterone
      (p=0.01) and higher plasma levels of the cytokine tumor necrosis factor (TNF)
      alpha (p < 0.05) after LPS challenge. Also the tianeptine-treated rats showed
      significantly reduced periodontal bone loss (p=0.01), enhanced plasma levels of
      TNF-alpha (p < 0.05), and transforming growth factor-1beta (p < 0.01), whereas no
      significant difference was found in corticosterone levels. CONCLUSION: An
      individual's responsiveness to danger signals, whether they are of immunological,
      chemical, or psychological origin, may be an important factor for explaining
      variability in susceptibility to periodontal disease. The results may provide new
      insight into the mechanisms of periodontal disease development, and open new
      vistas for disease prevention.

PMID- 16409254
TI  - Porphyromonas gingivalis-related cardiac cell apoptosis was majorly co-activated
      by p38 and extracellular signal-regulated kinase pathways.
AB  - BACKGROUND AND OBJECTIVE: Little is known about the pathogenesis of apoptosis
      caused in cardiac tissues by periodontitis pathogens. The purpose of this study
      was to determine the related effect of periodontal pathogen Porphyromonas
      gingivalis on cardiac cell apoptosis. METHODS: DNA fragmentation, nuclear
      condensation and activated apoptotic caspases were measured by agarose gel
      electrophoresis, nuclear DAPI (4',6-diamidine-2-phenylindole dihydrochloride)
      stain and western blotting analysis following the surrounding medium of P.
      gingivalis and/or pre-administration of SB203580 (p38 inhibitor), U0126 [mitogen
      activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2
      (ERK1/2) inhibitor], LY294002 [phosphoinositide 3-kinase (PI3K) inhibitor],
      cyclosporine A (CsA: calcineurin inhibitor), and Sp600125 [c-Jun N-terminal
      kinase (JNK) inhibitor] in cultured cardiac H9c2 cells. RESULTS: The surrounding
      medium of periodontal pathogen P. gingivalis increased DNA fragmentation, nuclear
      condensation and the activated apoptotic caspase-3, -8, and -9 proteins in H9c2
      cells. DNA fragmentation and nuclear condensation of H9c2 cells treated with P.
      gingivalis medium were completely blocked by SB203580 plus U0126 and were
      decreased after pre-administration of SB203580 only, U0126 only, LY294002, CsA,
      but were increased by Sp600125. CONCLUSION: Our findings suggest that the
      development of cardiac cell apoptosis can be directly induced by P. gingivalis
      medium. Porphyromonas gingivalis-related H9c2 cell apoptosis was mainly co
      activated by p38 and ERK pathways and may be involved in death receptor-dependent
      (caspase 8) and mitochondria (caspase 9)-dependent apoptotic pathways.
      Porphyromonas gingivalis-related cardiac cell apoptosis was also partially
      mediated by PI3K or calcineurin signaling pathways, whereas the JNK pathway might
      play a protective role in P. gingivalis-related cardiac cell apoptosis.

PMID- 16409255
TI  - Porphyromonas gingivalis affects host collagen degradation by affecting
      expression, activation, and inhibition of matrix metalloproteinases.
AB  - OBJECTIVE: Studies have shown that Porphyromonas gingivalis and host matrix
      metalloproteinases (MMPs) play important roles in the tissue destruction
      associated with periodontal disease. It is still unclear which MMPs or their
      inhibitors are regulated by P. gingivalis at the transcriptional and/or at the
      protein levels. Therefore, this study was conducted to determine what effects P.
      gingivalis supernatant has on the collagen degrading ability of human gingival
      fibroblasts (HGFs) and how it regulates the activation, mRNA expression, and
      inhibition of MMPs. METHODS: Culture supernatant from P. gingivalis ATCC 33277
      was added to HGFs cultured in six-well plates coated with Type I collagen. At
      certain time intervals, the cell conditioned media was collected for zymography
      and/or western blot analyses to determine the MMP and tissue inhibitor of MMPs
      (TIMP) protein levels. The cells were then removed and the collagen cleavage
      visualized by Coomassie blue staining. The mRNA expression of multiple MMPs and
      TIMPs by the treated and untreated HGFs was determined by reverse transcription
      polymerase chain reaction. RESULTS: The collagen in the six-well plates was
      degraded more rapidly by the HGFs treated with 10% v/v P. gingivalis supernatant.
      More active MMP-1, MMP-2, MMP-3, and MMP-14 were detected in the conditioned
      media from the HGFs treated with the P. gingivalis supernatant. TIMP-1, but not
      TIMP-2, was decreased in the presence of the P. gingivalis supernatant. MMP-1
      mRNA expression by the treated HGFs increased more than two-fold over the
      untreated HGFs. MMP-3 mRNA was unchanged, MMP-2 mRNA had a slight increase, MMP
      14 mRNA decreased, and MMP-15 increased. MMP-12 mRNA was induced in the P.
      gingivalis treated HGFs. TIMP-1 and TIMP-2 mRNA had a slight increase with P.
      gingivalis treatment. CONCLUSION: Porphyromonas gingivalis increased the collagen
      degrading ability of HGFs, in part, by increasing MMP activation and by lowering
      the TIMP-1 protein level, as well as by affecting the mRNA expression of multiple
      MMPs and TIMPs.

PMID- 16409256
TI  - A digital SLR or intra-oral camera: preference for acquisition within an image
      analysis system for measurement of disclosed dental plaque area within clinical
      trials.
AB  - OBJECTIVES: The aim of this investigation was to compare the accuracy and
      reproducibility of images acquired from two types of camera (digital SLR camera,
      Kodak DCS410, KJP, UK and an intra-oral camera, Schick Technologies, UK) for
      application within an imaging system used for the quantification of disclosed
      dental plaque. METHODS: Subjects refrained from brushing their teeth for 24 h.
      Their teeth were then disclosed with Erythrosin FDC Red 3 and duplicate sets of
      images were obtained by each examiner of the upper central and lateral incisors.
      Images were then saved and measured for dental plaque area. These data were used
      to calculate reliability. RESULTS: No statistically significant bias in the
      measurements of plaque area was found. The reliability results showed the method
      was reliable. However, the image analysis system incorporating the 35 mm SRL
      camera was more reliable for both operators, as demonstrated by their intra
      operator results. This was also collaborated by the inter-operator results.
      CONCLUSION: In this investigation the digital SLR camera combined with the image
      analysis system and frame permitted greater reliability of dental plaque surface
      area measurements than the digital intra-oral camera. This conclusion was derived
      both from the reliability data and from the perceived ease of use and flexibility
      of both camera types. When combined with the use of the custom-made frame, the
      images using the digital SLR camera were highly reproducible, confirming the
      systems application within clinical trials.

PMID- 16409257
TI  - Maturation-state dependent response of human periodontal ligament cells to an
      intermittent parathyroid hormone exposure in vitro.
AB  - BACKGROUND AND OBJECTIVES: Parathyroid hormone (parathyroid hormone) has been
      shown to be capable of exerting anabolic effects on bone when administered
      intermittently. We hypothesized that parathyroid hormone will modulate the
      response of periodontal ligament cells in terms of anabolic effects with respect
      to proliferation, differentiation and the production of key regulatory factors of
      bone remodeling such as osteoprotegerin and receptor activator of nuclear factor
      kappaB ligand (RANKL) in a maturation-state dependent manner. METHODS:
      Periodontal ligament cells were cultured from human bicuspids obtained from six
      patients. Following characterization, confluent and preconfluent periodontal
      ligament cells were challenged with parathyroid hormone (1-34) for 0, 1, 3, 6 or
      24 h within three incubation cycles of 48 h each. At harvest, the cell number,
      alkaline phosphatase specific activity and osteocalcin, osteoprotegerin and RANKL
      production were determined by means of semiquantitative polymerase chain reaction
      (PCR) and immunoassays. Dermal fibroblasts and MG63 osteoblast-like cells served
      as a reference. RESULTS: Intermittent parathyroid hormone treatment of confluent
      periodontal ligament cells caused a significant increase in proliferation (+32%
      maximum) whereas alkaline phosphatase activity, osteocalcin and osteoprotegerin
      decreased at the transcriptional and translational level (-59.7% maximum). In
      preconfluent periodontal ligament cells, parathyroid hormone induced a decrease
      in proliferation (-66.3% maximum) but an increase in differentiation and
      osteoprotegerin production (+49.2% maximum). RANKL was hardly detectable and
      unaffected by parathyroid hormone treatment. Similar results were obtained in
      MG63 cells, whereas parathyroid hormone stimulation did not alter any of the
      parameters examined in dermal fibroblasts. CONCLUSION: These results indicate
      that human periodontal ligament cells respond to an intermittent parathyroid
      hormone exposure with changes in proliferation, differentiation and
      osteoprotegerin production in a maturation-state dependent manner and therefore
      might be regulatorily involved in periodontal regeneration.

PMID- 16409259
TI  - Ivermectin: pharmacology and application in dermatology.
AB  - Ivermectin is a synthetic derivative of the antiparasitic class of compounds
      known as avermectins. It is a macrolide endectocide with activity against both
      endoparasites with cutaneous tropism (Strongyloides stercoralis, Ancylostoma
      braziliense, Cochliomyia hominivorax, Dermatobia hominis, Filaria bancrofti,
      Wucheria malayi, Onchocerca volvulus, Loa-loa) and ectoparasites such as
      Sarcoptes scabies, Pediculus humanus, Demodex folliculorum, and Cheyletiella sp.
      Ivermectin is of great interest in the treatment of patients with different forms
      of scabies, head lice, demodecidosis, cutaneous larva migrans, cutaneous larva
      currens, myiasis, and filariasis.

PMID- 16409258
TI  - Increased infiltration of CD1d and natural killer T cells in periodontal disease
      tissues.
AB  - BACKGROUND: Natural killer T (NKT) cells are a unique T lymphocyte subset that
      has been implicated in the regulation of immune responses associated with a broad
      range of diseases including autoimmunity, infectious diseases, and cancer. In
      contrast to conventional T cells, NKT cells are reactive to major
      histocompatibility complex (MHC) class I-like molecule CD1d. Considering the
      periodontitis having both aspects of infection and autoimmunity in nature, CD1d
      and reactive NKT cells are of particular importance. OBJECTIVE: The aim of the
      present study was to examine whether the expression of CD1 isoforms and
      Valpha24(+) invariant NKT cells is associated with different disease entities,
      namely gingivitis and periodontitis. MATERIAL AND METHODS: Immunohistochemical
      analysis was performed on cryostat sections of gingival tissues from 19 patients
      with periodontitis and eight patients with gingivitis using antibodies to CD1a,
      b, c, d, Valpha24(+) invariant NKT cells, CD83, CD3 and CD19. RESULTS: Although
      all four subsets of CD1 molecules were expressed in periodontal lesions, CD1d was
      most abundant. CD1d expression was more frequent in periodontitis than gingivitis
      and increased together with increase of invariant NKT cell infiltration. Double
      immunohistochemical staining showed co-expression of CD1d and CD19 on identical
      cells and proximate infiltration of CD1d(+) and invariant NKT cells. CONCLUSION:
      These findings suggest that CD1d-expressing B cells could activate NKT cells by
      CD1d-restricted manner and this NKT cell activation may play roles in
      pathogenesis of periodontal diseases.

PMID- 16409260
TI  - A sociodemographic, clinical study of patients with venous ulcer.
AB  - BACKGROUND: Venous ulcer is the most serious consequence of chronic venous
      insufficiency and is responsible for almost 70% of chronic leg ulcers. The main
      purpose of this research was to describe social, demographic and clinical
      characteristics of patients with venous ulcers and to identify some professional
      repercussions of this pathology. SUBJECTS AND METHODS: We evaluated patients with
      a clinical picture compatible with venous ulcer. The sociodemographic
      characteristics of the patients, and the clinical characteristics and
      professional repercussions of the pathology were studied. We used the ankle
      brachial index to identify associated arterial disease. The body mass index (BMI)
      was used for the classification of the nutritional condition of the patients.
      RESULTS: A total of 120 patients were included in the study (90 females and 30
      males; 80.8% White; 44.2% > 60 years old). Ninety-one per cent of the patients
      had been in education for less than 4 years, and 89.7% were on the poverty line.
      Thirty-five per cent were retired, 2.5% were receiving government help due to
      disease and 4.2% were unemployed. About 16% of patients were out of work due to
      the disease, and 49.2% presented some degree of disability in terms of work
      tasks. The ulcer area was less than 30 cm(2) in 69.1% of patients. The first
      ulcer episode occurred in 13.4 years on average, and 64.2% of patients had
      recurrent episodes. Females presented on average 5.65 pregnancies, and 75.4% of
      patients were overweight. CONCLUSION: Venous ulcer occurred mainly in the low
      income population, who presented with little formal education. Generally, the
      ulcers were present for a long time and were recurrent, with repercussions for
      the capabilities of patients to work.

PMID- 16409261
TI  - Lack of correlation between Helicobacter pylori infection and autologous serum
      skin test in chronic idiopathic urticaria.
AB  - BACKGROUND: There are controversial reports about the direct role of
      Helicobacterpylori infection in chronic idiopathic urticaria. The indirect role
      of H. pylori infection in the induction of pathogenetic antibodies is not fully
      elucidated either. This study aims to reveal the association of H. pylori
      infection with autologous serum skin test positivity in chronic idiopathic
      urticaria (CIU) patients. METHODS: A total of 47 patients (35 women, 12 men, age
      range 17-65 years) diagnosed as CIU were included in the study. Autologous serum
      skin test was performed on all patients. The patients were examined with a
      commercially available ELISA test for H. pylori-specific antibodies. Gastroscopy
      with mucosal biopsy and rapid urease tests were proposed to verify the presence
      of H. pylori infection. RESULTS: Helicobacter pylori infection was detected in 33
      of the 47 patients (70%). No significant relation was found between the
      autologous serum skin test positivity and the serological and histopathological
      presence of H. pylori infection. CONCLUSION: The results of our study suggest
      that chronic H. pylori infection does not appear to have a role in the induction
      of autoantibodies in CIU.

PMID- 16409262
TI  - Anaphylactic reaction to apple, banana and lychee: what is common between
      botanically disparate plant families?
AB  - We present the case of a 33-year-old nonatopic woman with multiple episodes of
      anaphylaxis after ingestion of different fruits. The fruits implicated were
      apple, banana and lychee: all of which belong to different and botanically
      disparate plant families. The reaction to apple and banana was confirmed by prick
      testing. There was no history of allergy to other agents that are known to have
      cross reactions with fruits, viz. latex or pollen. As such patients often do not
      present to dermatologists, we wish to highlight the rare but potentially fatal
      clinical entity of type I allergy to fruits without concomitant allergy to other
      common airborne/contact allergens. We also discuss the possible explanation of
      type I reaction to apparently unrelated fruits and the allergens involved in such
      reactions.

PMID- 16409263
TI  - Profile of acne patients in the Philippines requiring a second course of oral
      isotretinoin.
AB  - BACKGROUND: Oral isotretinoin (OI) is currently the gold standard in the
      treatment of moderately severe to severe acne vulgaris. Approximately 50-85% of
      patients achieve permanent cure with one course based on 1.0-2.0 mg/kg/body
      weight. It has been shown that a dosage of less than 1 mg/kg/body weight
      predisposed to noncure and required a second course for a permanent cure.
      OBJECTIVE: Purpose of this study was to describe the profile of acne patients in
      the Philippines requiring a second course of OI. METHODS: Charts of acne vulgaris
      patients given OI in a private dermatology clinic (SSJ) over a period of 10 years
      were reviewed and analyzed. All patients were given a total dose of 1 mg/kg/body
      weight (cumulative total dose of 120 mg/kg/body weight). RESULT: Of 240 patients
      taking OI included in the study, 193 completed the entire course. One hundred and
      43 (59.6%) were cured after one course and required no further therapy (control
      group: CG), 42 (17.5%) experienced relapse and were treated with topical therapy,
      and eight (3.3%) relapsed and required oral antibiotic plus topical therapy. Only
      47 patients (19.6%) required a second course of OI therapy (study group: SG).
      There was no difference between the two groups in age, sex, severity, and
      location of lesions. Two factors were found to be of statistically significant
      difference: Total dose actually taken with 103.5 mg/kg/body weight for the SG vs.
      118.55 mg/kg/body weight for the CG. Median duration of treatment was 6.7 months
      for the SG vs. 7.41 months for the CG, respectively. CONCLUSION: The profile of
      acne patients in the Philippines requiring a second course of OI is seen in those
      taking a mean cumulative dose (actual total dose) less than 120 mg/kg/body
      weight, with a mean actual duration of 6.7 months.

PMID- 16409264
TI  - Prevalence and risk factors for tinea pedis in Israeli soldiers.
AB  - BACKGROUND: Tinea pedis is a common infection in soldiers. However, prevalence
      and risk factors for tinea pedis in soldiers were investigated in only a few
      studies. OBJECTIVES: To investigate the prevalence and risk factors for tinea
      pedis in Israeli soldiers. METHODS: A cross-sectional study including interviews,
      clinical skin examination and mycological tests was performed in Israeli
      soldiers. The presence of tinea pedis was assessed using the Athlete's Foot
      Severity Index (AFSI), a scoring system that was developed in order to evaluate
      the presence and severity of tinea pedis. In soldiers with clinical evidence of
      tinea pedis (AFSI > 1), scrapings were taken for direct microscopic examination
      (20% KOH preparation) and fungal culture. Statistical analyses were performed
      using chi-square or Fisher's exact test for dichotomous variables (as needed), or
      t-tests for continuous variables. Logistic regression was used for multivariate
      analyses of dichotomous variables. RESULTS: Two hundred and twenty-three soldiers
      were included in the study: 205 men (91.9%) and 18 women (8.1%). Mean age was
      19.6 years (SD 1.0 year). Clinical point prevalence was 60.1%. Mycological point
      prevalence was 27.3%. Further analyses were performed using the clinical point
      prevalence. Univariate analyses demonstrated that the prevalence of tinea pedis
      varied with the setting of military training (basic training: 70.3%, advanced
      infantry training: 81.5%, armor commander training: 56.4% and armor officer
      training: 34.8%) and was associated with male gender, frequency of sock changes
      and the length of military service. A multivariate analysis demonstrated that
      tinea pedis was associated with the setting of the military training (OR 1.6, 95%
      CI 1.2-2.1) and male gender (OR 4.3, 95% CI 1.4-13.8); however, there was no
      association with hygiene measures (e.g. frequency of changing socks or sleeping
      with socks) or the length of military service. CONCLUSION: Tinea pedis is highly
      prevalent in Israeli soldiers. Association of tinea pedis with the setting of
      military training suggests that contagious spread may be an important risk
      factor. We suggest that environmental interventions should be planned to in order
      to decrease the morbidity of tinea pedis among soldiers.

PMID- 16409265
TI  - Direct triggers for ulceration in patients with venous insufficiency.
AB  - BACKGROUND: More than 80% of leg ulcers are caused by venous insufficiency. The
      actual causes of venous ulcers, beyond the presence of venous insufficiency, are
      rarely referred to in the literature. This study evaluates the direct triggers
      for ulceration in patients with venous insufficiency. METHODS: Sixty-four
      patients with 110 chronic venous ulcers, treated in the Chronic Wounds Clinic of
      Soroka University Medical Center from 1999 through 2002, were included in the
      study. In each patient, the actual trigger of ulceration was determined by
      history taking and reviewing of the medical chart. RESULTS: The actual triggers
      of ulceration, based on data for 64 patients with an overall total of 110 ulcers,
      were identified as follows: cellulitis (or erysipelas), 17 ulcers (15.4% of 110
      ulcers); penetrating injury, 13 ulcers (11.8%); contact dermatitis, 12 ulcers
      (10.9%); rapidly aggravating leg edema, 12 ulcers (10.9%); burn wound, seven
      ulcers (6.3%); dry skin with subsequent scratching, six ulcers (5.4%); blunt
      trauma, five ulcers (4.5%); deliberately self-inflicted trauma, five ulcers
      (4.5%); insect bite, two ulcers (1.8%); bleeding from a supeficial varicose vein,
      two ulcers (1.8%). In 29 ulcers (26.3%) no specific trigger was identified.
      CONCLUSIONS: The development of a cutaneous ulcer is not necessarily
      "spontaneous" and should not be attributed solely to the presence of venous
      insufficiency. In many cases, it is possible to identify a specific trigger that
      causes the ulceration. Clinical implementation of the above findings in routine
      examination and treatment of patients with venous insufficiency may prevent the
      development of venous ulcers.

PMID- 16409266
TI  - Familial gigantic melanocytosis.
AB  - BACKGROUND: Familial gigantic melanocytosis (FGM) is a rare disorder first
      described in 1984 and termed "familial melanopathy with gigantic melanocytes".
      The cause of the disorder is still unknown. Melanocytes in both hyper- and
      hypopigmented skin seem to be unable to deliver melanin to the surrounding
      keratinocytes. OBJECTIVE: In this study, we report four new cases of FGM.
      Electron microscopic examination was performed in a trial to shed more light on
      the underlying defect in this disorder. PATIENTS AND METHODS: Patients were
      examined clinically and biopsies were taken from both hyperpigmented and
      hypopigmented areas, and divided into two parts; one part was processed for
      routine microscopic examination with hematoxylin and eosin and Masson Fontana
      stains. The other portion of the biopsy was fixed in glutraldhyde 3% and
      processed for electron microscopic (EM) examination. RESULTS: By light
      microscopy, the patients' skin showed areas of hyperpigmented basal cells
      alternating with poorly pigmented areas. Hair follicles in the scalp biopsies
      showed the same pathology. By EM, pigmented areas showed gigantic melanocytes and
      heavily pigmented keratinocytes. Nonpigmented areas showed poorly pigmented
      keratinocytes and fewer, but also gigantic melanocytes. CONCLUSIONS: The raindrop
      like hypopigmentation in this disorder can be explained by a failure of
      melanocytes to deliver melanin to their surrounding keratinocytes. The cause of
      the presence of heavily pigmented keratinocytes in the hyperpigmented zones could
      not be determined. There is a strong possibility of a more widespread abnormality
      affecting not just the melanocytes.

PMID- 16409267
TI  - Effect of ethnicity on the risk of developing nonmelanoma skin cancer following
      long-term PUVA therapy.
AB  - BACKGROUND: Research demonstrating an increased incidence of skin cancer with
      psoralen plus ultraviolet A (PUVA) therapy has reflected the Caucasian
      experience. Our objective was to review the literature on skin cancer risk
      associated with long-term PUVA therapy in non-Caucasians. METHODS: Our analysis
      included 4,294 long-term PUVA patients in Japan, Korea, Thailand, Egypt, and
      Tunisia with a follow-up period of at least 5 years. RESULTS: The relative risk
      of PUVA patients developing nonmelanoma skin cancer relative to general
      dermatology outpatients was 0.86 [CI 0.36-1.35]. CONCLUSIONS: There does not
      appear to be an increased risk of nonmelanoma skin cancer with long-term PUVA
      therapy in Asian and Arabian-African populations. Therefore, in phototherapy risk
      assessment, it is important to consider the patient's skin phototype and the
      potential protection that more pigmented skin may confer.

PMID- 16409268
TI  - Association of HLA-DQA1 and DQB1 genes with vitiligo in Chinese Hans.
AB  - BACKGROUND: Vitiligo is an acquired depigmentary disorder of the skin and hair
      which results from selective destruction of melanocytes. Serological typing and
      genotyping of human leukocyte antigen (HLA) have shown discrepancies in HLA
      associations with vitiligo in different ethnic populations. METHODS: Polymerase
      chain reaction sequence-specific primer (PCR-SSP) method was used to analyze the
      distribution of HLA-DQA(1) and -DQB(1) alleles among 187 patients with vitiligo
      and 273 healthy controls through Epi Info version 6 package (Centers for Disease
      Control and Prevention, Atlanta, GA, USA). RESULTS: The frequencies of HLA
      DQA1*0302 (OR = 1.98, P(c) < 0.01), -DQB1*0303 (OR = 3.14, P(c) < 0.001), and 
      DQB1*0503 (OR = 3.36, P(c) < 0.05) alleles were significantly increased in
      patients with vitiligo compared with controls, and HLA-DQA(1)*0501 (OR = 0.40,
      P(c) < 0.01) allele frequency was highly decreased. HLA-DQA1*0302 (OR = 5.19,
      P(c) < 0.001), -DQA1*0601 (OR = 2.95, P(c) < 0.05), -DQB1*0303 (OR = 4.50, P(c) <
      0.001), and -DQB1*0503 (OR = 6.69, P(c) < 0.001) alleles were positively
      associated, whereas HLA-DQA1*0501 (OR = 0.05, P(c) < 0.001) allele was negatively
      associated with childhood vitiligo patients, and HLA-DQB1*0303 (OR = 2.76, P(c) <
      0.001) allele was positively associated with adult vitiligo patients compared
      with controls. The frequency of HLA-DQB1*0303 (OR = 3.72, P(c) < 0.001) allele
      was significantly increased in localized vitiligo patients vs. controls, whereas
      HLA-DQA1*0302 (OR = 2.47, P(c) < 0.01), -DQB1*0303 (OR = 2.67, P(c) < 0.01), and 
      DQB1*0503 (OR = 4.46, P(c) < 0.01) allele frequencies were significantly
      increased and -DQA1*0501 (OR = 0.27, P(c) < 0.01) allele frequency was highly
      decreased in generalized vitiligo patients. CONCLUSIONS: HLA-DQA1*0302, 
      DQA1*0601, -DQB1*0303, and -DQB1*0503 alleles could be susceptible alleles of
      vitiligo, while HLA-DQA1*0501 allele could be a protective allele in Chinese
      Hans. There may be different genetic backgrounds between vitiligo patients of
      childhood and adult, localized and generalized.

PMID- 16409269
TI  - Zosteriform metastatic transitional cell carcinoma.

PMID- 16409270
TI  - Angiokeratoma circumscriptum: a case report and review of the literature.

PMID- 16409271
TI  - Epithelioid leiomyosarcoma: case report and review of the literature.

PMID- 16409272
TI  - Giant annular dermatomyofibroma.

PMID- 16409273
TI  - Scrotal hair in identical twin infants.

PMID- 16409274
TI  - Tufted angioma.

PMID- 16409275
TI  - Disseminated cytomegalovirus infection involving the skin in a patient with
      chronic renal insufficiency.

PMID- 16409276
TI  - Acute febrile neutrophilic dermatosis (Sweet's syndrome) with erythema nodosum
      and anterior scleritis. A case report.

PMID- 16409277
TI  - Secondary extension of Hodgkin's disease to the skin with positive staining for
      EBV-encoded latent membrane protein.

PMID- 16409278
TI  - Pemphigoid gestationis post partum after changing husband.

PMID- 16409279
TI  - Kimura's disease in a Caucasian male treated with cyclosporine.

PMID- 16409280
TI  - Probable Werner's syndrome.

PMID- 16409281
TI  - Disposable skin hook.

PMID- 16409282
TI  - Comparing the efficiency of topical paromomycin with intralesional meglumine
      antimoniate for cutaneous leishmaniasis.

PMID- 16409283
TI  - Infant alopecia universalis: role of topical PUVA (psoralen ultraviolet A)
      radiation.

PMID- 16409284
TI  - Bullous tungiasis.

PMID- 16409285
TI  - Nicolau syndrome caused by piroxicam.

PMID- 16409286
TI  - Peculiar pigmentation: a study of 100 cases.

PMID- 16409288
TI  - Bilateral chylothorax in paediatric acute lymphoblastic leukaemia.

PMID- 16409289
TI  - Florid bone marrow haematogones in a child following treatment for acute
      lymphoblastic leukaemia.

PMID- 16409290
TI  - Location, movement and survival: the role of chemokines in haematopoiesis and
      malignancy.
AB  - Chemokines are a family of over 40 small (8 kDa) related proteins with the
      function of moving cells along a chemotactic gradient, either to organise cells
      within an organ or to facilitate the movement of leucocytes around the body.
      Mouse models have implicated the importance of the chemokine CXCL12 in
      haematopoiesis and this has lead to the use of the inhibitor AMD3100 for
      autologous transplantation. This review will briefly discuss the biology of
      chemokines and their role in haematopoiesis and haematological malignancy
      together with the possible benefits and hazards of therapeutic modification of
      the chemokine system.

PMID- 16409291
TI  - Thomas Addis of Edinburgh (1881-1949) and the coagulation cascade: 'for the
      greatest benefit done to practical medicine'.
AB  - Thomas Addis came of evangelical Scots stock; he was brought up to care for
      others less fortunate than himself, to know what he believed in and to defend it
      vigorously. Trained at the turn of the 19th and 20th centuries in a Scotland
      still recovering from wars and ecclesiastical schisms, yet producing record
      numbers of missionaries and many social improvements, he was a brilliant
      haematologist and innovative researcher. Moving to Stanford his career continued
      to blossom as a nephrologist whilst his concern for the less fortunate found
      expression in his espousal of communist principles. Only in his later years was
      he finally honoured for his many contributions to medicine, science and social
      issues.

PMID- 16409292
TI  - Guidelines on oral anticoagulation (warfarin): third edition--2005 update.

PMID- 16409293
TI  - Multilineage involvement of the fusion gene in patients with FIP1L1/PDGFRA
      positive hypereosinophilic syndrome.
AB  - Myeloproliferative hypereosinophilic syndrome (MHES) is a disorder characterised
      by male predominance, marked eosinophilia, splenomegaly, tissue fibrosis,
      elevated serum tryptase and the presence of the FIP1L1/PDGFRA fusion gene in
      peripheral blood mononuclear cells. The characteristic hypercellular bone marrow
      with dysplastic eosinophils and spindle-shaped mast cells suggest that multiple
      lineages may be involved in the clonal process. To determine which haematopoietic
      lineages are involved in MHES, we purified cells of specific lineages from
      patients with MHES and used nested reverse transcription polymerase chain
      reaction (RT-PCR), quantitative RT-PCR and fluorescence in situ hybridisation to
      analyse the purified cell populations for the presence of the fusion gene. The
      fusion gene was detected in eosinophils, neutrophils, mast cells, T cells, B
      cells and monocytes. These results suggest that the mutation arises in a
      pluripotential haematopoietic progenitor cell capable of giving rise to multiple
      lineages. The basis for the preferential expansion of eosinophils and mast cells
      remains unclear.

PMID- 16409294
TI  - Transactivation of CCL20 gene by Epstein-Barr virus latent membrane protein 1.
AB  - CCL20 is expected to play a crucial role in the initiation of immune responses
      and tumour growth. However, expression of CCL20 in Epstein-Barr virus (EBV)
      associated diseases has not been studied. We examined the contribution of EBV
      infection and EBV-encoded latent membrane protein (LMP)-1 to CCL20 expression.
      EBV infection and LMP-1 induced CCL20 mRNA expression in the EBV-negative Burkitt
      lymphoma (BL) cell lines and the embryonic kidney cell line. Histone deacetylase
      inhibitor-stimulated endogenous LMP-1 also induced CCL20 expression in an EBV
      positive BL cell line. Analysis of the CCL20 promoter showed that it was
      activated by LMP-1 C-terminal activation region (CTAR)-1 and CTAR-2. Co
      expression of IkappaB alpha, IkappaB beta, IkappaB kinase (IKK)alpha, IKKbeta,
      IKKgamma, nuclear factor (NF)-kappaB-inducing kinase and tumour necrosis factor
      receptor-associated factor 2 dominant-negative constructs with LMP-1 inhibited
      the activation of the CCL20 promoter by LMP-1, suggesting that LMP-1 induces
      CCL20 via NF-kappaB signalling. The requirement for the NF-kappaB-binding site in
      the CCL20 promoter in LMP-1 responsiveness was established. Our results indicate
      that activation of the NF-kappaB pathway by LMP-1 is required for the activation
      of CCL20 expression.

PMID- 16409295
TI  - Genomic and expression profiling identifies the B-cell associated tyrosine kinase
      Syk as a possible therapeutic target in mantle cell lymphoma.
AB  - Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By
      using a combination of genomic and expression profiling (Affymetrix GeneChip
      Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes
      relevant to MCL pathogenesis and that could represent new therapeutic targets.
      Recurrent genomic deletions and gains were detected. Genes were identified as
      overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including
      the cancer genes BCL2 and MYC. Among the transcripts with high correlation
      between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell
      receptor signalling. SYK was amplified at DNA level, as validated by fluorescence
      in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein
      levels in the JeKo-1 cell line. Low-level amplification, with protein
      overexpression of Syk was demonstrated by FISH in a small subset of clinical
      samples. After treatment with low doses of the Syk inhibitor piceatannol, cell
      proliferation arrest and apoptosis were induced in the cell line overexpressing
      Syk, while cells expressing low levels of Syk were much less sensitive. A
      combination of genomic and expression profiling suggested Syk inhibition as a new
      therapeutic strategy to be explored in lymphomas.

PMID- 16409297
TI  - The presence of IFNG 3/3 genotype in the recipient associates with increased risk
      for Epstein-Barr virus reactivation after allogeneic haematopoietic stem cell
      transplantation.
AB  - Recent studies have shown that interferon-gamma gene (IFNG) polymorphism
      constitutes a risk factor for acute and chronic graft-versus-host disease (GvHD)
      after allogeneic haematopoietic stem cell transplantation (HSCT). Patients with
      IFNG 3/3 have been found to be more prone to GvHD. This rather puzzling result,
      as 3/3 genotype is associated with a decreased IFN-gamma production, was
      investigated in the present study in the context of Epstein-Barr virus (EBV)
      reactivation. Microsatellite polymorphism (CA)n within the first intron of IFNG
      gene was assessed in 83 HSCT recipients and related to EBV load. Quantification
      of EBV copies was performed by a real-time polymerase chain reaction in
      peripheral blood cells taken from the patients 2-3 months after HSCT. It was
      found, that patients having IFNG 3/3 genotype presented with a high number of EBV
      copies (over 10/10(5) blood cells) when compared with the recipients with other
      IFNG genotypes (10/14 vs. 17/69, P < 0.001). This association was independent of
      recipient's age, underlying disease, conditioning regimen, type of donor, source
      of stem cells or pretransplant donor and recipient EBV serological status. Thus
      IFNG 3/3 genotype, known to be associated with a decreased IFN-gamma production,
      appeared as a factor significantly contributing to the risk of EBV reactivation
      after allogeneic HSCT.

PMID- 16409296
TI  - Direct targeting of genetically modified tumour cells to Fc gammaRI triggers
      potent tumour cytotoxicity.
AB  - Expression of the type I receptor for Fc domain of immunoglobulin (Ig)G (Fc
      gammaRI or CD64) is restricted to myeloid effector cells, such as monocytes,
      macrophages and a subset of dendritic cells. Previous work has indicated a role
      for Fc gammaRI in antibody-dependent phagocytosis and lysis of tumour cells. We
      hypothesised that tagging of tumour cells with an anti-Fc gammaRI single chain Fv
      (sFv) may facilitate targeting to this receptor on effector cells, thereby
      initiating tumour cytotoxicity. A vector encoding the sFv for an Fc gammaRI
      specific antibody (H22), linked to the transmembrane domain of platelet-derived
      growth factor was constructed. Transfected tumour cells expressed high surface
      levels of functional H22-sFv, which greatly enhanced susceptibility for
      phagocytosis and lysis by monocytes and macrophages. The expression of H22-sFv
      evoked the ability of tumour cells to directly activate monocytes, as evidenced
      by phosphorylation of mitogen-activated protein kinase and secretion of the
      inflammatory cytokines interleukin (IL)-1beta, tumour necrosis factor-alpha and
      IL-6. Moreover, growth of tumour cells in mice expressing H22-sFv was profoundly
      delayed (or absent) in transgenic mice expressing human Fc gammaRI. These results
      demonstrated that tumour cells can be readily modified to activate cell effector
      mechanisms, a strategy that may be useful for in vivo targeting in patients.

PMID- 16409298
TI  - Tissue factor pathway inhibitor anticoagulant activity: risk for venous
      thrombosis and effect of hormonal state.
AB  - Full-length tissue factor pathway inhibitor (TFPI) is assumed to be biologically
      more important than truncated TFPI because of its stronger anticoagulant effect
      in the diluted prothrombin time (dPT) assay. We have developed a dPT-based assay
      for TFPI anticoagulant activity. Here, we report the effect of hormonal state on
      TFPI anticoagulant activity and whether TFPI anticoagulant activity assesses the
      risk for deep-vein thrombosis (DVT) better than conventional TFPI assays. We
      undertook a case-control study of 474 patients with DVT and 474 controls and
      compared the odds ratio (OR) for DVT for those with low TFPI anticoagulant
      activity with the ORs obtained for TFPI free and total antigen, and TFPI
      chromogenic substrate activity. Hormonal state affected clot time in dPT, but
      this effect was ameliorated by anti-TFPI antibodies. Low TFPI anticoagulant
      activity gave an OR of 1.5 (0.97-2.1) for DVT, similar to the ORs obtained with
      conventional TFPI assays, ranging from 1.2 to 1.4. Individuals low in both the
      activity assays obtained an OR of 5.9 (1.7-20). We concluded that the effect of
      hormonal state on dPT was mediated through TFPI, and a dPT-based assay of TFPI
      anticoagulant activity did not assess the risk for DVT better than conventional
      TFPI assays.

PMID- 16409300
TI  - Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: effects of
      catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de
      novo protein synthesis.
AB  - The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of
      transformed or proliferating cells. However, little is known regarding its
      ability to induce apoptosis in terminally differentiated cells, such as
      neutrophils. Because neutropenia has been reported in some cancer patients after
      AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue
      that has never been investigated. Herein, we found that AT-induced neutrophil
      apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil
      superoxide production and did not induce mitochondrial generation of reactive
      oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic
      granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox)
      mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2,
      reversed AT-induced apoptosis and degradation of the cytoskeletal proteins
      gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein
      synthesis, which was reversed by catalase. Cycloheximide partially reversed AT
      induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase
      dependent mechanism and via de novo protein synthesis. H2O2 is of major
      importance in AT-induced neutrophil apoptosis but its production does not
      originate from nicotinamide adenine dinucleotide phosphate dehydrogenase
      activation and mitochondria. Cytoskeletal structures other than microtubules can
      now be considered as novel targets of AT.

PMID- 16409299
TI  - Bacitracin reveals a role for multiple thiol isomerases in platelet function.
AB  - The platelet-specific integrin alphaIIb beta3 has endogenous thiol isomerase
      activity associated with the CXXC motifs within the beta subunit. Using a highly
      purified form of bacitracin, a thiol isomerase inhibitor, we now provide further
      evidence of the functional significance of this enzymatic activity in integrin
      activation. In addition, we demonstrate a role for multiple thiol isomerases in
      platelet function. This bacitracin prevented platelet aggregation to thrombin and
      collagen, and directly inhibited alphaIIb beta3 activation, as detected by PAC-1
      binding. In parallel, bacitracin inhibited the endogenous thiol isomerase
      activity of purified alphaIIb beta3 with a 50% inhibitory concentration of 15.5
      micromol/l. In order to determine whether the effects of bacitracin are solely
      mediated by inhibition of integrin enzymatic activity, we examined integrin
      independent indices of platelet activation. We found bacitracin inhibited both
      platelet secretion (CD62P and CD63) and thromboxane (TxA2) production, with
      complete inhibition at different concentrations. Thus, we demonstrated a role for
      multiple thiol isomerases in platelet function. Taken together, these studies
      support a role for the endogenous integrin thiol isomerase activity in activation
      of alphaIIb beta3 and highlight the novel regulation of platelet function by
      other, as yet undefined thiol isomerases.

PMID- 16409301
TI  - P210 Bcr-abl tyrosine kinase interaction with histone deacetylase 1 modifies
      histone H4 acetylation and chromatin structure of chronic myeloid leukaemia
      haematopoietic progenitors.
AB  - The BCR-ABL fusion gene, originating from the balanced (9;22) translocation, is
      the molecular hallmark and the causative event of chronic myeloid leukaemia
      (CML). The interactions of its p210 protein constitutively activated and
      improperly confined to the cytoplasm with multiple regulatory signals of cell
      cycle progression, apoptosis and self-renewal, induce the illegitimate
      enlargement of clonal haematopoiesis and genetic instability that drives its
      progression towards the fully transformed phenotype of blast crisis. However, its
      effects on the basic transcription machinery and chromatin remodelling are
      unknown. Our study underscored histone H4 hyperacetylation associated with p210
      tyrosine kinase in vitro and in vivo and its role in BCR-ABL transcription.
      Histone H4 hyperacetylation proceeds, at least partly, from the 'loss of
      function' of histone deacetylase 1 protein, a critical component of Rb-mediated
      transcriptional repression, in consequence of its cytoplasmatic
      compartmentalisation.

PMID- 16409302
TI  - Impaired interaction of alpha-haemoglobin-stabilising protein with alpha-globin
      termination mutant in a yeast two-hybrid system.
AB  - Alpha-thalassaemia caused by alpha-globin gene termination codon mutations
      (alphaT-globin) has been explained by their inherent mRNA instability and by
      oxidative damage arising from the presence of membrane-bound alphaT-globin
      chains. To better understand the latter phenomenon, a yeast two-hybrid system was
      used to assay the interaction between alphaT-globin and its molecular chaperone,
      alpha-haemoglobin-stabilising protein (AHSP) and impaired binding of alphaT
      globin with AHSP compared with alpha(wild-type)-globin was observed.

PMID- 16409304
TI  - Atypical presentation of acute promyelocytic leukaemia.

PMID- 16409303
TI  - HLA-DRB1 polymorphism is associated with Kell immunisation.
AB  - K immunisation is observed in some polytransfused patients and pregnant women but
      does not occur in all cases of K incompatibility. This study analysed the role of
      genetic background in this selective response to K antigen by investigating HLA
      DRB1 alleles associated with K immunisation in a southern European population.
      HLA-DRB1 genotyping was performed by polymerase chain reaction sequence-specific
      oligonucleotide/sequence-specific primer procedures in 54 K immunised patients
      and 200 healthy controls. The frequency of HLA-DRB1*11 was significantly higher
      in K immunised patients than healthy controls: 31 of 54 (57%) vs. 56 of 200 (28%)
      (P(c) < 0.001). In the remaining K immunised HLA-DRB1*11-negative patients, the
      frequency of HLA-DRB1*13 was increased: 14 of 23 (61%) vs. 49 of 144 in healthy
      controls (34%) (P < 0.02). The combined frequency of the two HLA-DRB1 alleles
      (HLA-DRB1*11 and HLA-DRB1*13) was 83% in K immunised patients when compared with
      52% in healthy controls (P(c) < 0.001). K and k differ by a single amino acid
      T193 (M). The DRB1*11 and DRB1*13 alleles share a HLA-DRB1 gene sequence
      containing S in position 13, D in 70 and A in 74, and coding for the P4 pocket
      within the HLA-DR binding groove. This feature of the HLA-DRB1 gene could be
      involved in the K peptide presentation through a polymorphism ligand specific for
      the T193 (M) of K. In conclusion, this study demonstrated a high frequency of HLA
      DRB1*11 or HLA-DRB1*13 alleles in K immunised patients, which could be due to
      specific K peptide presentation by HLA-DR molecules.

PMID- 16409306
TI  - Chronic obstructive pulmonary disease outcomes: can we now compare apples with
      apples?

PMID- 16409307
TI  - Lung transplantation for chronic obstructive pulmonary disease at St Vincent's
      Hospital.
AB  - BACKGROUND: Lung transplantation (LTx) offers selected patients with end-stage
      chronic obstructive pulmonary disease (COPD) an improved quality of life and
      possibly enhanced survival. AIM: To determine local outcomes of LTx for COPD we
      analysed 173 consecutive heart-LTx (n = 8), single LTx (SLTx; n = 99) and
      bilateral LTx (BLTx; n = 66) carried out at a single institution during 1989-2003
      for smoking-related emphysema (E) (n = 112) and emphysema related to alpha-1
      antitrypsin deficiency (AATD) (n = 61). METHODS: There were 98 men and 75 women
      with a mean age of 50 +/- 6 years (standard deviation) (range 32-63 years).
      Median waiting time was 113 days (interquartile range (IQR) 50-230 days), and
      median inpatient stay was 13 days (IQR 9-21 days). RESULTS: Perioperative
      survival (30 days) was 95% with deaths from sepsis (n = 5), cerebrovascular
      accident (n = 3) and multiorgan failure (n = 1). Mean follow-up period was 1693
      +/- 1302 days (2-4,805 days). The 1-, 5- and 10-year survivals (%) were similar
      for patients with E and AATD (P = 0.480 log rank) at 86 +/- 5, 57 +/- 7 and 31 +/
      11, respectively, but 1- and 5-year survivals for E were higher after BLTx than
      after SLTx (97 +/- 2 and 81 +/- 8 vs 85 +/- 4 and 47 +/- 6) (P = 0.015).
      Pretransplant body mass index, forced expiratory volume in 1 second, forced vital
      capacity, PaCO(2), PaO(2), six-minute walk distance, home oxygen use, age, sex,
      cytomegalovirus donor-recipient mismatch, cardiopulmonary bypass use, year of
      transplant and ischaemic time did not influence survival after LTx. Increasing
      donor age was a survival risk factor for patients with E but not for those with
      AATD (hazard ratio 1.043; 95%confidence interval 1.014-1.025). CONCLUSION:
      Survival after LTx for COPD is similar to survival for other forms of solid organ
      transplantation, in part reflecting risk factor management.

PMID- 16409308
TI  - Using a clinical pathway and education to reduce inappropriate prescribing of
      enoxaparin in patients with acute coronary syndromes: a controlled study.
AB  - AIMS: To evaluate efficacy of a pathway-based quality improvement intervention on
      appropriate prescribing of the low molecular weight heparin, enoxaparin, in
      patients with varying risk categories of acute coronary syndrome (ACS). METHODS:
      Rates of enoxaparin use retrospectively evaluated before and after pathway
      implementation at an intervention hospital were compared to concurrent control
      patients at a control hospital; both were community hospitals in south-east
      Queensland. The study population was a group of randomly selected patients (n =
      439) admitted to study hospitals with a discharge diagnosis of chest pain,
      angina, or myocardial infarction, and stratified into high, intermediate, low
      risk ACS or non-cardiac chest pain: 146 intervention patients (September-November
      2003), 147 historical controls (August-December 2001) at the intervention
      hospital; 146 concurrent controls (September-November 2003) at the control
      hospital. Interventions were active implementation of a user-modified clinical
      pathway coupled with an iterative education programme to medical staff versus
      passive distribution of a similar pathway without user modification or targeted
      education. Outcome measures were rates of appropriate enoxaparin use in high-risk
      ACS patients and rates of inappropriate use in intermediate and low-risk
      patients. RESULTS: Appropriate use of enoxaparin in high-risk ACS patients was
      above 90% in all patient groups. Inappropriate use of enoxaparin was
      significantly reduced as a result of pathway use in intermediate risk (9%
      intervention patients vs 75% historical controls vs 45% concurrent controls) and
      low-risk patients (9% vs 62% vs 41%; P < 0.001 for all comparisons). Pathway use
      was associated with a 3.5-fold (95% CI: 1.3-9.1; P = 0.012) increase in
      appropriate use of enoxaparin across all patient groups. CONCLUSION: Active
      implementation of an acute chest pain pathway combined with continuous education
      reduced inappropriate use of enoxaparin in patients presenting with intermediate
      or low-risk ACS.

PMID- 16409309
TI  - Access to tumour necrosis factor inhibitors for rheumatoid arthritis treatment
      under the Australian Pharmaceutical Benefits Scheme: are we on target?
AB  - BACKGROUND: Access to tumour necrosis factor inhibitors (TNFI) for the treatment
      of rheumatoid arthritis under the Australian Pharmaceutical Benefits Scheme (PBS)
      is governed by a set of arrangements, operational from August 2003. Patients must
      meet strict criteria for both starting and continuing TNFI. Examination of
      utilization data is important for assessing the broader implications of
      arrangements for access to expensive pharmaceuticals under schemes such as the
      PBS. AIM: To examine the uptake of TNFI over the first year of subsidized
      availability of etanercept under the PBS, and to compare these data to the
      predicted utilization and expenditure. METHODS: Collection and analysis of
      prescription and expenditure data for the three listed TNFI: etanercept,
      infliximab and adalimumab processed under the PBS for the period August 2003 to
      July 2004. RESULTS: A total of 8,053 prescriptions for TNFI was reimbursed at a
      total cost of 15.2 m Australian dollars. The total PBS expenditure on etanercept
      was just over 14 m Australian dollars, 14% of the predicted annual expenditure.
      The relative per capita uptake of etanercept was highest in the Australian
      Capital Territory and lowest in the Northern Territory. More than 50% of
      prescriptions for etanercept were for concessional patients (7.3 m Australian
      dollars). CONCLUSION: Prescription rates and expenditure on etanercept were
      substantially below those forecast over the first year. There are opportunities
      to adjust the PBS restrictions for subsidized access to TNFI to benefit more
      patients.

PMID- 16409310
TI  - Epidemiology of the functional gastrointestinal disorders diagnosed according to
      Rome II criteria: an Australian population-based study.
AB  - BACKGROUND: Population-based studies of the prevalence of all functional
      gastrointestinal disorders (FGID) using the Rome II criteria are lacking. It is
      also not certain whether subjects who meet the Rome II criteria for an FGID are
      different in terms of demographic and psychological characteristics from those
      subjects meeting exclusively the more restrictive Rome I criteria. AIM: To
      determine whether using the more restrictive Rome I criteria would result in a
      more biologically determined group of FGID than when the Rome II is applied.
      METHODS: Subjects included individuals aged 18 years and older (n = 1,225) from
      the Penrith population who were initially surveyed with the Penrith District
      Health Survey in 1997. Subjects were sent a self-report questionnaire that
      contained items on gastrointestinal symptoms applying the Rome II criteria.
      Subjects were also assessed on psychological and personality factors and on
      physical and mental functioning. RESULTS: A total of 36.1% (n = 275) of
      respondents was diagnosed with an FGID according to Rome II criteria. The five
      most prevalent FGID were functional heartburn (10.4%), irritable bowel syndrome
      (8.9%), functional incontinence (7.6%), proctalgia fugax (6.5%) and functional
      chest pain (5.1%). Subjects meeting Rome II only criteria for FGID scored
      significantly higher on measures of psychological caseness and emotionality than
      Rome I only subjects, and these were independently associated with meeting Rome I
      only versus Rome II only criteria for FGID. CONCLUSION: The Rome II criteria FGID
      are common and do not appear to identify a vastly different group of FGID
      sufferers compared with the earlier Rome I criteria.

PMID- 16409311
TI  - Providing guidelines and education is not enough: an audit of gentamicin use at
      The Royal Melbourne Hospital.
AB  - BACKGROUND: Aminoglycoside antibiotics are commonly prescribed for the treatment
      of Gram-negative infections. Appropriate dosing and therapeutic monitoring of
      aminoglycosides are important because these agents have a narrow therapeutic
      index. AIM: To audit gentamicin use at our hospital, focusing on selection of the
      initial dose and therapeutic monitoring practices, and to compare the results
      against recommendations in the existing hospital aminoglycoside guidelines, which
      had recently been promoted to doctors. METHODS: This audit included all
      inpatients receiving gentamicin at The Royal Melbourne Hospital from 1 February
      to 12 March 2004. The principal researcher checked the drug charts of all
      inpatients to identify those receiving gentamicin and collected data from the
      medical records and the pathology database. Doses were considered 'concordant' if
      the dose given was within the recommended dosing range +/-20 mg. RESULTS: A total
      of 132 courses of gentamicin was included in the study. Gentamicin was prescribed
      for prophylaxis in 31.1% of courses. Thirty-six per cent of patients prescribed
      gentamicin were more than 65 years of age. Eighty-two per cent of the gentamicin
      used therapeutically was given as a single daily dose. Sixty-six per cent of
      gentamicin initial dosing was not in accordance with existing hospital
      guidelines. Seventy-seven per cent of gentamicin courses requiring therapeutic
      drug monitoring received such monitoring; however, in only 8.8% of these was the
      monitoring conducted according to guidelines. CONCLUSION: Aminoglycoside
      prescribing practices at our hospital are suboptimal, despite ready access to
      prescribing guidelines. Provision of a guideline and education sessions with
      doctors do not necessarily lead to widespread adoption of recommended practices.
      We suggest that changes to hospital systems related to prescribing and monitoring
      of aminoglycosides are required.

PMID- 16409313
TI  - Bioethics in ethically pluralist societies.

PMID- 16409312
TI  - Non-invasive multislice computed tomography coronary angiography for imaging
      coronary arteries, stents and bypass grafts.
AB  - Abstract Multislice computed tomography (MSCT) is evolving rapidly and available
      data suggest that MSCT coronary angiography may be a reliable and accurate non
      invasive imaging modality of coronary arteries. Current generations of MSCT
      scanners have high sensitivity and specificity for diagnosing native coronary
      artery disease and coronary bypass graft occlusion. The performance of MSCT in
      the evaluation of stent patency is still being assessed. In comparison with
      conventional selective coronary angiography (SCA), MSCT is non-invasive, cheaper
      and it has the advantages of imaging plaque compositions as well as assessment of
      luminal patency. Nevertheless, the role of MSCT in the management of coronary
      artery disease is yet to be fully defined.

PMID- 16409314
TI  - Health-care problems of Turner syndrome in the adult woman: a cross sectional
      study of a Victorian cohort and a case for transition.
AB  - The aim of this study was to assess current care and to survey comorbidity in a
      cohort of 39 adult women with Turner syndrome in Victoria. Patients with Turner
      syndrome (TS) drift away from medical care as they achieve adulthood, despite the
      need for regular surveillance and management of associated conditions, which
      would reduce morbidity and prevent complications. Clinical assessment was
      undertaken for 39 women with TS, mean age 30.1 (+/-11.7) years and information
      was gathered through personal communication regarding past growth hormone use,
      oestrogen treatment, hearing loss and health problems. Twenty-four (63.2%) had
      regular follow-up, but only 17 (43.6%) had adequate recommended surveillance for
      comorbidities. Forty-three percent had two or more cardiovascular risk factors.
      Thirty-four (87.2%) were identified with one or more associated disorders.
      Uterine size was of normal adult dimensions in patients who had received
      oestrogen before age of 15 years. Adult care for adults with TS is suboptimal and
      assessment of comorbidities remains sporadic. Adequate transition guidelines and
      patient education are needed for long-term management of women with TS, to impact
      on quality of life and longevity.

PMID- 16409315
TI  - High-rate pulmonary involvement in autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) has extrapancreatic complications such as Sjogren's
      syndrome, retroperitoneal fibrosis and sclerosing cholangitis. We studied 30
      patients with AIP. Of these, we identified pulmonary involvement in four patients
      during follow up. Among them, two patients had respiratory failure. They showed
      good response to steroid therapy, but a higher dose of prednisolone was necessary
      to maintain remission than that required in biliary involvement. Elevation of
      immunoglobulin G(4) and Krebs von den Lungen-6 levels were characteristic of
      pulmonary involvement. They may be useful for early detection of pulmonary
      complication.

PMID- 16409316
TI  - Medical image: reversible posterior leucoencephalopathy syndrome.

PMID- 16409317
TI  - Rapid preparation of patients with Graves' hyperthyroidism for urgent
      thyroidectomy.

PMID- 16409318
TI  - Medications and green urine.

PMID- 16409319
TI  - Physicians and the pharmaceutical industry.

PMID- 16409322
TI  - The effect of mineral trioxide aggregate on the apexification and periapical
      healing of teeth with incomplete root formation.
AB  - AIM: To evaluate the influence of mineral trioxide aggregate (MTA) on
      apexification and periapical healing of teeth in dogs with incomplete root
      formation and previously contaminated canals and to verify the necessity of
      employing calcium hydroxide paste before using MTA. METHODOLOGY: Twenty premolars
      from two 6-month old dogs were used. After access to the root canals and complete
      removal of the pulp, the canal systems remained exposed to the oral environment
      for 2 weeks. Canal preparation was then carried out using Hedstrom files, under
      irrigation with 1% sodium hypochlorite, 1 mm short of the radiographic apex.
      After drying, the canals of two premolars in each dog were left empty (control
      group). The other eight teeth in each animal were divided into two experimental
      groups. The apical thirds of the canals of group 1 were filled with MTA. In the
      teeth of group 2, the canals were dressed with a calcium hydroxide-propylene
      glycol paste. After 1 week, the paste was removed and the apical third was filled
      with MTA. All teeth were restored with reinforced zinc oxide cement (IRM) and
      amalgam. The animals were killed 5 months later, and blocks of the teeth and
      surrounding tissues were submitted to histological processing. The sections were
      studied to evaluate seven parameters: formation of an apical calcified tissue
      barrier, level of barrier formation, inflammatory reaction, bone and root
      resorption, MTA extrusion, and microorganisms. Results of experimental groups
      were analysed by Wilcoxon's nonparametric tests and by the test of proportions.
      The critical value of statistical significance was 5%. RESULTS: Significant
      differences (P < 0.05) were found in relation to the position of barrier
      formation and MTA extrusion. The barrier was formed in the interior of the canal
      in 69.2% of roots from MTA group only. In group 2, it was formed beyond the
      limits of the canal walls in 75% of the roots. MTA extrusion occurred mainly in
      roots from group 2. There was similarity between the groups for the other
      parameters. CONCLUSIONS: Mineral trioxide aggregate used after root canal
      preparation favoured the occurrence of the apexification and periapical healing.
      The initial use of calcium hydroxide paste was not necessary for apexification to
      occur, and has shown to be strongly related to the extrusion of MTA and formation
      of barriers beyond the limits of the root canal walls.

PMID- 16409323
TI  - Efficacy of various concentrations of NaOCl and instrumentation techniques in
      reducing Enterococcus faecalis within root canals and dentinal tubules.
AB  - AIM: To evaluate the efficacy of 0.5%, 2.5% and 5.25% sodium hypochlorite (NaOCl)
      as intracanal irrigants associated with hand and rotary instrumentation
      techniques against Enterococcus faecalis within root canals and dentinal tubules.
      METHODOLOGY: A total of 180 extracted human premolar teeth were infected for 21
      days with E. faecalis. The specimens were divided into 12 groups, as follows:
      group 1: 5.25% NaOCl + Hybrid technique (Valdrighi et al. 1998); group 2: 5.25%
      NaOCl + nickel-titanium (NiTi) rotary technique 4 mm shorter than the apex (by
      FOP-UNICAMP); group 3: 5, 25% NaOCl + NiTi rotary technique (Hero 642); group 4:
      2.5% NaOCl +Hybrid technique; group 5: 2.5% NaOCl + NiTi rotary technique 4 mm
      shorter than the apex; group 6: 2.5% NaOCl + NiTi rotary technique (Hero 642);
      group 7: 0.5% NaOCl + Hybrid technique; group 8: 0.5% NaOCl + NiTi rotary
      technique 4 mm shorter than the apex; group 9: 0.5% NaOCl + NiTi rotary technique
      (Hero 642); group 10: sterile saline solution + Hybrid technique; group 11:
      sterile saline solution + NiTi rotary technique 4 mm shorter than the apex; group
      12: sterile saline solution + NiTi rotary technique (Hero 642). Canals were
      sampled before and after preparation. After serial dilution, samples were plated
      onto brain heart infusion (BHI) agar, and the colony forming units (CFU) that
      were grown were counted. The teeth were sectioned into three thirds and dentine
      chips were removed from the canals with conical burs. The samples obtained with
      each bur were immediately collected into test tubes containing BHI broth, and
      were incubated at 37 degrees C and plated onto BHI agar. The CFU were counted and
      analysed. RESULTS: At all depths and thirds of the root canals and for all
      techniques used, 5.25% NaOCl was shown to be the most effective irrigant solution
      tested when dentinal tubules were analysed, followed by 2.5% NaOCl. No
      differences among concentrations in cleaning the canals were found. CONCLUSIONS:
      Especially at higher concentrations, NaOCl, was able to disinfect the dentinal
      tubules, independent of the canal preparation technique used.

PMID- 16409324
TI  - Tubular sclerosis rather than the smear layer impedes dye penetration into the
      dentine of endodontically instrumented root canals.
AB  - AIM: To evaluate the effect of different root canal irrigating regimes on dentine
      penetration of Patent Blue dye. METHODOLOGY: Eighty extracted single-rooted human
      mandibular premolar teeth with narrow root canals were prepared using ProFile
      instruments. After each instrument, canals were irrigated with 1% sodium
      hypochlorite. Subsequently, teeth were randomly assigned to receive a 10 mL rinse
      of aqueous 17% (w/v) ethylenediaminetetraacetic acid or tap water for 2 or 10
      min, followed by a final rinse with a 2% Patent Blue dye solution for 2 or 10 min
      (eight groups, n = 10 teeth per group). Teeth were then horizontally sectioned 3,
      6 and 9 mm from the apex. Sections were digitally photographed and dye
      penetration was calculated as percentage of total dentine area using NIH Image J.
      Values were compared using one-way anova and Bonferroni correction with the alpha
      type error set at <0.05. Representative tooth sections from all groups were
      further analysed using scanning electron microscopy. RESULTS: No significant
      impact of irrigating protocols on dye penetration was found. Dye penetration was
      significantly (P < 0.001) greater in the coronal than middle, and in middle than
      in apical root thirds. When observed microscopically, irrigant penetration was
      independent of the presence of a smear layer, but was rather a function of
      tubular sclerosis. CONCLUSIONS: Tubular sclerosis, a physiological phenomenon
      that starts in the third decade of life in the apical root region and advances
      coronally with age, was the main factor influencing penetrability of root
      dentine.

PMID- 16409325
TI  - Ex vivo biocompatibility tests of regular and white forms of mineral trioxide
      aggregate.
AB  - AIM: To examine the genotoxicity and cytotoxicity of regular and white mineral
      trioxide aggregate (MTA) ex vivo by the single-cell gel (comet) assay and trypan
      blue exclusion test, respectively. METHODOLOGY: Aliquots of 1 x 10(4) Chinese
      hamster ovary cells were incubated at 37 degrees C for 3 h with grey and white
      forms of MTA at final concentrations ranging from 1 to 1,000 microg mL(-1). The
      negative control group was treated with vehicle control phosphate buffer solution
      for 3 h at 37 degrees C and the positive control group was treated with methyl
      metasulfonate (at 1 microg mL(-1)) for 1 h at 37 degrees C. After incubation, the
      cells were centrifuged at 180 g for 5 min and washed twice with fresh medium and
      resuspended with fresh medium. Each individual treatment was repeated three times
      consecutively to ensure reproducibility. Parameters from single-cell gel (comet)
      and cytotoxicity assays were assessed by the Kruskal-Wallis nonparametric test.
      RESULTS: Neither compounds produced genotoxic effects with respect to the single
      cell gel (comet) assay in all concentrations evaluated. In the same way, the dose
      response relationships of all compounds tested at concentrations ranging from 1
      to 1,000 microg mL(-1) on cell viability assessed by the trypan blue assay
      displayed no statistically significant differences (P > 0.05) for either
      endodontic material. CONCLUSIONS: Regular (grey) and white MTA are not genotoxins
      and do not induce cellular death.

PMID- 16409326
TI  - The adhesion between fibre posts and composite resin cores: the evaluation of
      microtensile bond strength following various surface chemical treatments to
      posts.
AB  - AIM: To evaluate the influence of various surface treatments to fibre posts on
      the microtensile bond strength with different composite resins. METHODOLOGY: A
      total of 110 fibre posts were randomly divided into five groups, according to the
      surface pre-treatment performed. Group 1: immersion in 24% H(2)O(2) for 10 min
      and silanization for 60 s; group 2: immersion in 10% H(2)O(2) for 20 min and
      silanization for 60 s; group 3: immersion in 4% hydrofluoric acid gel for 60 s
      and silanization for 60 s; group 4: silanization of the post surface for 60 s and
      application of the bonding agent G-Bond; group 5: silanization of the post
      surface for 60 s (control group). After treatment, two posts were randomly
      selected from each group to evaluate the morphological aspect of the post surface
      with scanning electron microscopy. The remaining posts in each group were divided
      into five subgroups of five posts each, which differed in the type of composite
      resin used for the core build-up. Post-core strength were calculated and the
      differences among experimental groups were analysed with two-way anova and the
      Tukey test (alpha = 0.05). RESULTS: The post-core strengths achieved in groups 1
      and 2 were significantly higher (P < 0.05), than those of groups 3, 4 and 5. The
      post-core strength in the control group was significantly lower (P < 0.05) than
      all other groups. CONCLUSIONS: Hydrogen peroxide and hydrofluoric acid both
      modified the surface morphology of fibre posts and with silane, significantly
      enhanced the interfacial strength between them and core materials.

PMID- 16409328
TI  - Ex vivo study of the efficacy of H-files and rotary Ni-Ti instruments to remove
      gutta-percha and four types of sealer.
AB  - AIM: To compare the efficacy of ProFile rotary Nickel-Titanium (Ni-Ti)
      instruments and Hedstroem-files (H-files) combined with Gates-Glidden (GG) drills
      during removal of gutta-percha root fillings used in combination with one of the
      four representative sealers. METHODOLOGY: Forty-eight single-rooted human teeth,
      with fully formed apices and straight root canals were used. The root canals were
      accessed and instrumented using a stepback technique with H-files. They were
      randomly assigned to four groups and subsequently filled with a combination of
      lateral and vertical condensation of gutta-percha and one of the following
      sealers: Roth 811, AH26, Endion and Roekoseal. The root fillings were removed 1
      year later, using either H-files in combination with GG drills or the ProFile Ni
      Ti system. Teeth were then grooved longitudinally and split. The amount of gutta
      percha and sealer remaining on the root canal walls was traced and scored
      visually with the aid of a stereomicroscope. The scores were analysed and
      statistically compared with the Kruskal-Wallis test between the ProFile and H
      file groups, as well as among the four sealer subgroups. Two samples from each
      group were studied under the scanning electron microscope to enhance inspection
      of canal walls and remaining material. RESULTS: Sealer remnants were observed
      with both techniques mainly in the middle and apical third of the root canal. The
      ProFile system and the H-files were associated with similar amounts of remaining
      filling material (P > 0.05). In the cervical third of the root canal all sealer
      remnants were removed with both techniques. In the middle and apical third AH26
      was associated with a statistically significant greater quantity of remnants on
      the root canal walls with both removal techniques (P < 0.05). Endion, Roth 811
      and Roekoseal were associated with approximately the same amount of filling
      material in the middle third of the root canal (P > 0.05), whereas in the apical
      third Endion was associated with significantly more remnants of filling material
      than the other two sealers with either ProFile or H-files (P < 0.05).
      CONCLUSIONS: None of the methods used for the removal of root fillings was
      totally effective, especially in the apical third of the root canal.

PMID- 16409327
TI  - Cytotoxicity of materials used in perforation repair tested using the V79
      fibroblast cell line and the granulocyte-macrophage progenitor cells.
AB  - AIM: To compare the cytotoxicity of materials used to repair perforations using
      permanent V79 fibroblasts and murine granulocyte-macrophage progenitor cells (CFU
      GM). METHODOLOGY: Set specimens from amalgam, glass-ionomer, SuperEBA, N-Rickert,
      MTA and gutta-percha were eluted with culture medium for 72 h and their
      cytotoxicities were assessed by incubating the extracts with V79 and bone marrow
      derived progenitors for 24 h and 7 days, respectively. Cytotoxicity on V79 cells
      was judged using the total nucleic acid content (NAC), neutral red uptake (NRU)
      and reduction of the tetrazolium salt (MTT). The number of bone marrow CFU-GM
      colonies determined in clonal cultures stimulated with recombinant murine
      granulocyte-macrophage colony-stimulating factor was used to assess cytotoxicity
      to progenitor cells. Statistical analyses were conducted using the one-way
      analysis of variance and Tukey's test where appropriate. RESULTS: All materials
      were cytotoxic in both cell systems; however, CFU-GM was more sensitive to the
      extracts than V79 cells. A similar rank order of toxicity was observed in V79
      cells using the NAC and the MTT assays: glass-ionomer > N-Rickert congruent with
      SuperEBA > gutta-percha > amalgam congruent with MTA (P < 0.05). In contrast, the
      NRU test exhibited a lower sensitivity to MTA, gutta-percha and amalgam extracts.
      In the clonal culture assay, the toxicity was less pronounced in the presence of
      gutta-percha, SuperEBA and MTA. Similar cellular responses were found by placing
      the set specimens directly in the clonal culture dishes. CONCLUSIONS: The
      sensitivity of toxicity depended on the choice of the endpoint and the cell
      culture system. Nevertheless, MTA was ranked as the least cytotoxic cement in
      both cell systems.

PMID- 16409329
TI  - Removal efficacy of various calcium hydroxide/chlorhexidine medicaments from the
      root canal.
AB  - AIM: To compare the efficiency of removing calcium hydroxide
      [Ca(OH)(2)]/chlorhexidine (CHX) (gel), Ca(OH)(2)/CHX (solution) and
      Ca(OH)(2)/saline pastes with the use of instrumentation and irrigation with
      sodium hypochlorite and ethylene diamine tetraacetic acid (EDTA) solutions.
      Moreover the role of the patency file in the cleanliness of the apical third of
      the root canal was evaluated. METHODOLOGY: Sixty-four human single-rooted teeth
      with straight canals were used. Root canal preparation was performed with a
      stepback technique using Hedstrom (H) files. Teeth were randomly assigned to
      three groups and subsequently filled with one of the pastes: Ca(OH)(2)/CHX (gel),
      Ca(OH)(2)/CHX (solution) and Ca(OH)(2)/saline paste. The medicaments were removed
      10 days later using instrumentation and irrigation with 1% sodium hypochlorite
      and 17% EDTA, with or without obtaining patency of the apical foramen with a size
      10 H-file. The crowns were removed at the cemento-enamel junction and the roots
      were grooved longitudinally and split into halves. Images of all halves were
      acquired with the use of a flatbed scanner. A scoring system of 1 to 4 was used
      to assess the amount of residue on the cervical, middle and apical third of the
      canal. Data were subjected to statistical analysis using Kruskal-Wallis and Mann
      Whitney tests, with Bonferroni correction, at 95% confidence level (P < 0.05).
      RESULTS: Remnants of medicament were found in all experimental teeth regardless
      of the experimental material used and the use of the patency file. When examining
      the root canal as a whole, Ca(OH)(2)/CHX (gel) paste was associated with
      significantly larger amount of residue, whereas the Ca(OH)(2)/CHX (solution)
      paste was associated with less amount (P < 0.05) than the other two medicaments
      with or without the use of a patency file. CONCLUSIONS: None of the techniques
      used in this study removed the inter-appointment root canal medicaments
      effectively; the use of the patency file facilitated removal of more of the
      medicament in the apical third of those straight canals.

PMID- 16409330
TI  - Incidence and antimicrobial susceptibility of Porphyromonas gingivalis isolated
      from mixed endodontic infections.
AB  - AIM: To investigate the prevalence of Porphyromonas gingivalis in root canals of
      infected teeth with periapical abscesses and to investigate the antimicrobial
      susceptibility of this species to some frequently prescribed antibiotics.
      METHODOLOGY: Samples were obtained from 70 root canals of abscessed teeth.
      Microbial sampling, isolation and bacterial identification were accomplished
      using appropriate culture methods for anaerobic species. The antimicrobial
      susceptibility of the 20 strains of P. gingivalis isolated was determined by
      using the E-test. The antimicrobial agents tested were amoxicillin, amoxicillin +
      clavulanate, azythromycin, benzylpenicillin, cephaclor, clindamycin,
      erythromycin, metronidazole and tetracycline. RESULTS: A total of 352 individual
      strains, belonging to 69 different species, were isolated. Eighty three percent
      of the strains were strict anaerobes and 47.5% of the isolated bacteria were Gram
      negative. Porphyromonas gingivalis was found in 20 root canals and was most
      frequently found in symptomatic cases. Statistically, the presence of P.
      gingivalis was related to purulent exudates and pain on palpation (both P <
      0.05). All P. gingivalis strains were sensitive to amoxicillin, amoxicillin +
      clavulanate, cephaclor, clindamycin, benzylpenicyllin, metronidazole and
      tetracycline. The lowest range of minimum inhibitory concentration (MIC) (0.026
      0.125 microg mL(-1)) was observed against amoxicillin + clavulanate and
      clindamycin. The lowest MIC 90 was observed against clindamycin (0.064 microg mL(
      1)). One strain was resistant to erythromycin and eight strains were resistant to
      azythromycin. CONCLUSION: Porphyromonas gingivalis pathogen is isolated with
      frequency from root canals of infected teeth with periapical abscesses.
      Amoxicillin, as well as amoxicillin-clavulanic acid and benzylpenicillin were
      effective against P. gingivalis.

PMID- 16409331
TI  - A comparative study of root canal preparation with NiTi-TEE and K3 rotary Ni-Ti
      instruments.
AB  - AIM: To evaluate and compare several parameters of curved root canal preparation
      using two different Ni-Ti systems: NiTi-TEE (Sjoding Sendoline, Kista, Sweden)
      and K3 (Sybron Endo, Orange County, CA, USA). METHODOLOGY: Fifty extracted
      mandibular molars with mesial root canal curvatures ranging from 20 to 40 degrees
      were divided into two groups. In one group, 50 root canals were instrumented
      using NiTi-TEE files to an apical size 30; 0.04 taper (the largest available size
      at the time of this study). In the other group, 50 root canals were prepared with
      K3 instruments to an apical size 45; 02 taper. Both systems were used in a
      crowndown manner, with copious NaOCl (3%) irrigation and a chelating agent
      (Calcinase Slide, lege artis, Dettenhausen, Germany), employing torque-controlled
      motors. For assessment of shaping ability, pre- and postinstrumentation
      radiographs and cross-sectional photographs of canals were taken and changes in
      canal curvature and root canal diameter documented. Cleaning ability was
      evaluated by investigating specimens of the apical, medial and coronal third of
      the root canal wall under a scanning electron microscope using 5-score indices
      for debris and smear layer. Procedural errors (instrument separations,
      perforations, apical blockages, loss of working length) and working time were
      recorded. Nonparametric anova was used to compare straightening of canal
      curvatures, canal cross-sections and canal wall cleanliness (P < 0.05), whereas
      working time was analysed using the parametric anova (P < 0.05). RESULTS: Both Ni
      Ti systems maintained curvature well: the mean degree of straightening was 0.2
      degrees for NiTi-TEE and 0.4 degrees for K3 with no statistical significance
      between the groups. Post-instrumentation cross-sections of the root canals
      revealed an acceptable contour (round or oval) in 50.6% of cases for the NiTi-TEE
      group and in 65.3% of cases for the K3 group. The difference was not significant.
      The SEM investigation of canal walls showed equally good debris removal for both
      systems: NiTi-TEE prepared canal walls in 74.7% of cases with scores I and II; K3
      achieved these scores in 78.7% of cases. For smear layer, NiTi-TEE and K3 only
      received good scores (I and II) in 38.7% and 40% of canal wall specimens,
      respectively. For both parameters, no significant differences were found between
      groups. File fractures did not occur, but loss of working length was observed in
      one case following the preparation with NiTi-TEE and in three cases during K3
      instrumentation. Mean working time was significantly shorter for NiTi-TEE (170 s)
      than for K3 (208 s). CONCLUSIONS: Both systems maintained original canal
      curvature well and were safe to use. Whilst debridement of canals was considered
      satisfactory, both systems failed to remove smear layer sufficiently.

PMID- 16409332
TI  - Cemental tear: a case report.
AB  - AIM: To report a case of a cemental tear. SUMMARY: A case is reported of a
      patient with a history of trauma, root canal treatment and retreatment procedures
      to eliminate recurring sinus tracts. An exploratory surgery, extraction, and
      biopsy resulted in a diagnosis of cemental tear. KEY LEARNING POINTS: * The
      detachment of a fragment of cementum is described as a cemental tear. * Cemental
      tears have been reported in the periodontal literature associated with localized,
      rapid periodontal breakdown. Common causative factors are aging and traumatic
      occlusion but the exact aetiology is unknown. * Trauma may be considered as a
      potential aetiologic factor for cemental tears in addition to occlusal traumatism
      and aging.

PMID- 16409333
TI  - Preventing excessive pre-operative fasting: national guideline or local protocol?

PMID- 16409334
TI  - The pharmacoeconomics of peri-operative beta-blocker therapy.
AB  - It is widely recommended that beta-blockade be used peri-operatively as it may
      reduce the incidence of postoperative cardiovascular complications including
      death. However, there are few data concerning the cost-effectiveness of such
      strategies. We have analysed the pharmacoeconomics of acute beta-blockade using
      data from eight prospective peri-operative studies in which patients underwent
      elective non-cardiac surgery, and in which the incidence of adverse side-effects
      of treatment, as well as clinical outcomes, have been reported. The costs of
      treatment were based on the NHS reference costs for 2004. From these data, the
      number-needed-to-treat (NNT) to prevent a major cardiovascular complication
      (including cardiovascular death) in high-risk patients was 18.5. This is
      comparable to the NNT for peri-operative statin therapy. The incremental cost of
      peri-operative beta-blockade (costs of drug acquisition and of treating
      associated adverse drug events) was 67.80 pounds sterling per patient. This
      results in a total cost of 1254.30 pounds sterling per peri-operative
      cardiovascular complication prevented. However, there is evidence that in
      patients at lower cardiovascular risk, beta-blockers may be potentially harmful,
      since their adverse effects (hypotension, bradycardia) may outweigh their
      potential cardioprotective effects.

PMID- 16409335
TI  - Radiation exposure of trainee anaesthetists.
AB  - This prospective study was conducted to determine the level of radiation exposure
      of trainee anaesthetists working in urology, orthopaedics and radiology
      environments. Anaesthetists wore lithium fluoride thermoluminescent dosimeter
      (TLD) badges over a 6-month period. The position of badges was standardised at
      the collar site (TLD1) and at waist level (TLD2). Area specific dosimeters were
      used and exchanged between anaesthetists. Of a total of 723 procedures,
      anaesthetists were exposed to radiation in 33% of procedures in orthopaedics, 30%
      in urology and 39% in radiology. The mean (SD) exposure time to radiation per
      case was significantly greater in orthopaedics than in urology (9.2 (4) min vs.
      4.2 (2) min). The radiation exposure per case was highest in radiology (19.2 (22)
      min). The net combined exposure over a 6-month period was 0.2177 mSv in urology,
      0.4265 mSv in orthopaedics and 3.8457 mSv in radiology. The combined exposure was
      less than the 20 mSv recommended as the maximum exposure per year. Our data does
      not support the need for routine dosimetric monitoring of anaesthetists working
      in the above settings.

PMID- 16409336
TI  - Anchoring of the internal jugular vein with a pilot needle to facilitate its
      puncture with a wide bore needle: a randomised, prospective, clinical study.
AB  - In this prospective, randomised study, consented adult patients of both genders
      were divided into two groups. In group 1 (n = 79) patients, during internal
      jugular vein cannulation, the pilot needle was removed before the wide bore
      needle (18G) puncture. In group 2 (n = 78) patients, the internal jugular vein
      was anchored by leaving the pilot needle in place during wide bore needle
      puncture. In demographically similar groups, the first attempt success rate
      improved from 64% in group 1 to 81% in group 2 (p < 0.05). Internal jugular vein
      puncture was more frequently detected at the entry of the needle with anchoring
      (group 2: 78%) than without (group 1: 53%); p < 0.05. Ultrasonography of a
      further 30 internal jugular vein punctures in each group demonstrated that the
      anchoring manoeuvre (group 2b) significantly (p < 0.05) prevented an indenting
      effect of the puncture needle, with a higher vertical to horizontal diameter
      ratio of the internal jugular vein when there was anchoring (0.97; SD 0.004) than
      without pilot needle anchoring (0.65; SD 0.008). In conclusion, when using
      surface landmarks, anchoring of the internal jugular vein with the pilot needle
      facilitated its puncture.

PMID- 16409337
TI  - Comparison of tolerance of facemask vs. mouthpiece for non-invasive ventilation.
AB  - This prospective, single centre, randomised, cross-over study compares patient
      tolerance of the facemask and mouthpiece for delivery of non-invasive ventilation
      in an intensive care unit. Twenty-seven patients with acute respiratory failure
      were scheduled for two 45-min sessions of non-invasive ventilation with facemask
      and mouthpiece. The order of the sessions was chosen at random. Nurses and
      patients assessed the tolerance of both techniques using a visual analogue scale.
      The time spent by nurses and the changes in respiratory parameters were recorded.
      The facemask was better tolerated than the mouthpiece; all the cases of non
      invasive ventilation withdrawal (n = 5) occurred with mouthpieces (p = 0.026).
      Less nursing time was required using the facemask for the 22 patients who
      underwent both procedures (p = 0.01). However, the difference in tolerance scores
      was not significant. Non-invasive ventilation with both facemask and mouthpiece
      improved the P(a)o(2)/F(i)o(2) ratio, increased the pH and decreased the
      P(a)co(2). Only non-invasive ventilation with the facemask lowered the
      respiratory rate. The facemask appears to be a better initial choice for non
      invasive ventilation when compared to mouthpiece, but both can be effective.

PMID- 16409338
TI  - Effect of an anaesthesia department led critical care outreach and acute pain
      service on postoperative serious adverse events.
AB  - We examined whether a combined critical care outreach and acute pain service
      comprising both medical and nursing staff from the Department of Anaesthesia
      would decrease the incidence of postoperative serious adverse events in a
      hospital with an established Medical Emergency Team. We called this combined
      service IMPACT: Inpatient Management of acute Pain and Advice on Clinical
      Treatment. We conducted a prospective, before-and-after trial with a baseline
      phase (319 patients) of standard acute pain management followed by the IMPACT
      phase (271 patients), during which the IMPACT team systematically reviewed high
      risk postoperative patients for the first three days after their return to the
      general wards. The incidence of serious adverse events decreased from 23 events
      per 100 patients to 16 events per 100 patients. The 30-day mortality decreased
      from 9% to 3%, p = 0.004. An acute pain service providing critical care outreach
      may improve postoperative outcome but the workload is considerable.

PMID- 16409339
TI  - A randomised double-blind controlled study evaluating the hypothermic effect of
      150 microg morphine during spinal anaesthesia for Caesarean section.
AB  - We studied the hypothermic effect of adding 150 microg morphine during spinal
      anaesthesia in 60 parturients scheduled for elective caesarean section. All the
      parturients received intrathecal injection of a solution containing 150 mug
      morphine or normal saline in addition to 10-12 mg hyperbaric bupivacaine 0.5%. In
      both groups, a significant decrease in body temperature was noted. There was no
      difference in the area under the curve for temperature against time for the two
      groups; however, the maximum decrease in temperature from baseline was
      significantly larger after morphine than after saline injection (mean (SD) 1.11
      (0.61) degrees C vs 0.76 (0.39) degrees C, respectively; p = 0.01) and the time
      to nadir temperature was significantly longer (59.5 (17.6) min vs 50.4 (15.9)
      min, respectively; p = 0.047). The lowest temperature observed in the morphine
      group was 34.3 degrees C. We conclude that intrathecal injection of 150 microg
      morphine intensified the intra-operative hypothermic effect of bupivacaine spinal
      anaesthesia for caesarean section.

PMID- 16409340
TI  - Awake insertion of the laryngeal mask airway using topical lidocaine and
      intravenous remifentanil.
AB  - We assessed the use of intravenous remifentanil for the insertion of the
      laryngeal mask airway in 10 healthy awake volunteers, a technique primarily
      developed to facilitate functional magnetic resonance imaging studies of
      anaesthesia. Each volunteer received 200 microg glycopyrronium intravenously.
      Topical airway anaesthesia was effected by 4 ml nebulised lidocaine 4%, followed
      by 12 sprays of lidocaine 10%. Remifentanil was subsequently infused to achieve
      an initial target effect-site concentration of 2 ng.ml(-1); increments of 1
      ng.ml(-1) were allowed with the maximum effect-site concentration limited to 6
      ng.ml(-1). Insertion of the laryngeal mask airway was successful on the first
      attempt in all cases. The median (IQR [range]) target effect-site remifentanil
      concentration at insertion was 2.5 (2-3 [2-4]) ng.ml(-1). All volunteers were co
      operative during the procedure and only one reported discomfort. Sore throat was
      a complication in all volunteers. We conclude that the technique allows
      successful insertion of the laryngeal mask airway in healthy awake volunteers
      under conditions that were safe and reproducible.

PMID- 16409341
TI  - Obesity and obstetric anaesthesia.
AB  - The prevalence of obesity continues to increase despite preventive strategies.
      Obese parturients are at increased risk of having either concurrent medical
      problems or superimposed antenatal diseases such as pre-eclampsia and gestational
      diabetes. Moreover, they have a tendency to labour abnormally contributing to
      increased instrumental delivery and Caesarean section. Obesity is a risk factor
      for anaesthesia related maternal mortality. Morbidly obese women must be
      considered as high-risk and deserve an anaesthetic consultation during their
      antenatal care. The significant difficulty in administering epidural analgesia
      should not preclude their use in labour. A more liberalised use of regional
      techniques may be a means to further reduce anaesthesia-related maternal
      mortality in the obese population. The mother's life should not be jeopardised to
      save a compromised fetus. Prophylactic placement of an epidural catheter when not
      contraindicated in labouring morbidly obese women would potentially decrease
      anaesthetic and perinatal complications associated with attempts at emergency
      provision of regional or general anaesthesia. Early mobilisation, aggressive
      chest physiotherapy and adequate pain control are essential components of
      effective postoperative care.

PMID- 16409342
TI  - Life-threatening pulmonary hypertension and right ventricular failure
      complicating calcium and phosphate replacement in the intensive care unit.
AB  - A 43-year-old man developed septic shock and acute lung injury after surgery to
      drain an ischiorectal abscess. In the intensive care unit he initially improved
      but developed severe hypoxaemia, right ventricular failure and pulmonary
      hypertension 90 min after receiving intravenous calcium gluconate and potassium
      phosphate, best explained by the formation of a calcium-phosphate precipitant
      that resulted in aggregate anaphylaxis. His rapid deterioration and lack of
      response to conventional therapies necessitated support with extracorporeal
      membrane oxygenation that was life saving. This adverse event has altered local
      practice regarding calcium and phosphate replacement and has implications for all
      intensive care units.

PMID- 16409343
TI  - Multiple cardiac arrests following an overdose of caffeine complicated by
      penetrating trauma.
AB  - A 28-year-old man was admitted following a massive caffeine overdose and a self
      inflicted gunshot wound in an apparent suicide attempt. Although initially stable
      on admission, he subsequently suffered multiple cardiac arrests and generalised
      seizures within 23 h of admission; over the next 48 h, he developed
      rhabdomyolysis. The importance of early management in caffeine overdose is
      highlighted.

PMID- 16409344
TI  - Botulism in a pregnant intravenous drug abuser.
AB  - A case of botulism is reported in a heroin-abusing parturient who initially
      presented with lethargy and slurred speech. The diagnostic difficulty,
      complications, intensive care and anaesthetic management of this case are
      discussed, with particular reference to the pregnancy and the effects of both
      botulism and its empirical treatment on the fetus. A short review is provided of
      a condition that has seen a marked increase in its incidence since 2000.

PMID- 16409345
TI  - Levosimendan: a promising treatment for myocardial stunning?
AB  - We report a case of a 55-year-old male undergoing major orofacial cancer surgery.
      A stent to the left anterior descending artery had been implanted for ischaemic
      heart disease 3 years previously. Twenty-four hours after uneventful anaesthesia
      and surgery, the patient developed myocardial infarction and cardiogenic shock.
      Immediate percutaneous transluminal coronary angioplasty, intra aortic balloon
      counterpulsation, and catecholamine therapy failed to stabilise haemodynamics. In
      light of successful reperfusion therapy and an only moderate elevation of
      troponin I, myocardial stunning rather than myonecrosis was considered to be the
      major contributor to life-threatening left ventricular failure. Therefore, the
      calcium-sensitising drug levosimendan, which exerts positive inotropic activity
      without increasing myocardial oxygen demand, was administered as a rescue
      medication. Within 24 h, levosimendan resulted in decreased filling pressures,
      reduced left ventricular end-diastolic volume, and augmented systemic pressures.
      Seven days following surgery, the patient was discharged from the intensive care
      unit in good clinical condition.

PMID- 16409346
TI  - Reducing the risk of prion transmission in anaesthesia.

PMID- 16409347
TI  - Overdose of propofol in a child.

PMID- 16409348
TI  - Cardiovascular changes after induction of anaesthesia.

PMID- 16409349
TI  - First presentation of myasthenia gravis.

PMID- 16409350
TI  - Use of carbon dioxide extubation.

PMID- 16409351
TI  - The CobraPLA.

PMID- 16409352
TI  - Another problem with adhesive drapes.

PMID- 16409353
TI  - Anaesthesia for endobronchial brachytherapy.

PMID- 16409354
TI  - The management of accidental dural puncture.

PMID- 16409355
TI  - Trainees' experiences of difficult and failed intubation in obstetrics.

PMID- 16409356
TI  - Repeated nerve blocks with clonidine, fentanyl and bupivacaine for trigeminal
      neuralgia.

PMID- 16409357
TI  - Aortic dissection after forceful coughing.

PMID- 16409359
TI  - Loose adhesive in anaesthetic circuit.

PMID- 16409358
TI  - Autotriggering of pressure support ventilation during general anaesthesia.

PMID- 16409360
TI  - More problems with Luer lock connections.

PMID- 16409361
TI  - More on epidural wings.

PMID- 16409362
TI  - Assistance with axillary blocks.

PMID- 16409364
TI  - A response to 'Tramadol and severe serotonin syndrome'.

PMID- 16409365
TI  - A response to 'Airway management before, during and after extubation: a survey of
      practice in the United Kingdom and Ireland'.

PMID- 16409366
TI  - A response to 'Living with the European Clinical Trials Directive: one year on'.

PMID- 16409367
TI  - In response to 'Another use for ultrasound in the ICU'.

PMID- 16409376
TI  - Homology of echinoderm radial nerve cords and the chordate neural tube???

PMID- 16409378
TI  - Evolutionary and functional analysis of the tailless enhancer in Musca domestica
      and Drosophila melanogaster.
AB  - To further understand the evolutionary dynamics of the regulatory interactions
      underlying development, we expand on our previous analysis of hunchback and
      compare the structure and function of the tailless enhancer between Musca
      domestica and Drosophila melanogaster. Our analysis shows that although the
      expression patterns and functional protein domains of tll are conserved between
      Musca and Drosophila, the enhancer sequences are unalignable. Upon closer
      investigation, we find that these highly diverged enhancer sequences encode the
      same regulatory information necessary for Bicoid, Dorsal, and the terminal system
      to drive tll expression. The binding sites for these transcription factors differ
      in the sequence, number, spacing, and position between the Drosophila and Musca
      tll enhancers, and we were unable to establish homology between binding sites
      from each species. This implies that the Musca and Drosophila Bcd-binding sites
      have evolved de novo in the 100 million years since these species diverged.
      However, in transgenic Drosophila embryos the Musca tll enhancer is able to drive
      the same expression pattern as endogenous Drosophila tll. Therefore, during the
      rapid evolution of enhancer sequences individual binding sites are continually
      lost and gained, but the transcriptional output is maintained by compensatory
      mutations in cis and in trans.

PMID- 16409379
TI  - Conservation of retinal circadian rhythms during cavefish eye degeneration.
AB  - Regressive evolution of morphological features is a common evolutionary event.
      However, the relationship between structural degeneration and loss of
      physiological function is often unclear because the ancestral and derived states
      of a character are usually not available for comparison. Here, we report studies
      on retinomotor rhythms during development of the blind cavefish Astyanax
      mexicanus, a single teleost species consisting of a sighted surface-dwelling form
      (surface fish) and several blind cave-dwelling (cavefish) forms. The eyed and
      blind forms of Astyanax diverged from a common sighted ancestor within the past
      million years. Despite the absence of functional eyes in cavefish adults, optic
      primordia are formed in embryos, but then gradually arrest in development,
      degenerate, and sink into the orbits. Although a layered retina is formed in
      cavefish embryos, it is deficient in photoreceptor cells, and in some cases the
      retinal pigment epithelium has lost its pigmentation. We show that the capacity
      to exhibit light-entrained retinomotor rhythms has been conserved in the
      degenerating embryonic eyes of two different Astyanax cavefish populations. The
      results indicate that loss of circadian retinal function does not precede and is
      therefore not required for eye degeneration in the blind cavefish.

PMID- 16409380
TI  - Functional constraint underlies 60 million year stasis of Dipteran testis
      specific beta-tubulin.
AB  - How do proteins evolve while maintaining their function? Previous studies find a
      highly stringent structure/function relationship between the Drosophila
      melanogaster testis-specific tubulin beta2 and the spermtail axoneme, such that
      small changes in the beta2 protein render it unable to generate a motile axoneme.
      This raises the question, how does beta2 evolve while maintaining its function?
      To address this question we cloned full- and partial-length beta2 sequences from
      17 species of Drosophila and Hirtodrosophila flies spanning 60 Myr of evolution.
      Not a single amino acid difference is coded among them-beta2 maintains its
      function by not evolving. We also performed gene genealogical analyses to
      determine ortholog/paralog relationships among insect tubulins. We find that the
      Lepidopteran and Dipteran testis-specific beta-tubulins are likely orthologs, and
      surprisingly, despite functioning in the same structure, the Lepidopteran
      orthologs are evolving rapidly. We argue that differences in tubulin isoform use
      in the testes cause the Dipteran axoneme to be less evolvable than the
      Lepidopteran axoneme, which has facilitated the evolution of a unique amino acid
      synergism in Drosophila and Hirtodrosophilabeta2 that is resistant to change,
      contributing to its evolutionary stasis.

PMID- 16409381
TI  - Conservation and divergence in the AGAMOUS subfamily of MADS-box genes: evidence
      of independent sub- and neofunctionalization events.
AB  - The MADS-box gene AGAMOUS (AG) plays a key role in determining floral meristem
      and organ identities. We identified three AG homologs, EScaAG1, EScaAG2, and
      EScaAGL11 from the basal eudicot Eschscholzia californica (California poppy).
      Phylogenetic analyses indicate that EScaAG1 and EScaAG2 are recent paralogs
      within the AG clade, independent of the duplication in ancestral core eudicots
      that gave rise to the euAG and PLENA (PLE) orthologs. EScaAGL11 is basal to core
      eudicot AGL11 orthologs in a clade representing an older duplication event after
      the divergence of the angiosperm and gymnosperm lineages. Detailed in situ
      hybridization experiments show that expression of EScaAG1 and EScaAG2 is similar
      to AG; however, both genes appear to be expressed earlier in floral development
      than described in the core eudicots. A thorough examination of available
      expression and functional data in a phylogenetic context for members of the AG
      and AGL11 clades reveals that gene expression has been quite variable throughout
      the evolutionary history of the AG subfamily and that ovule-specific expression
      might have evolved more than twice. Although sub- and neofunctionalization are
      inferred to have occurred following gene duplication, functional divergence among
      orthologs is evident, as is convergence, among paralogs sampled from different
      species. We propose that retention of multiple AG homologs in several paralogous
      lineages can be explained by the conservation of ancestral protein activity
      combined with evolutionarily labile regulation of expression in the AG and AGL11
      clades such that the collective functions of the AG subfamily in stamen and
      carpel development are maintained following gene duplication.

PMID- 16409382
TI  - Developmental regulation of skull morphology II: ontogenetic dynamics of
      covariance.
AB  - Canalization may play a critical role in molding patterns of integration when
      variability is regulated by the balance between processes that generate and
      remove variation. Under these conditions, the interaction among those processes
      may produce a dynamic structure of integration even when the level of variability
      is constant. To determine whether the constancy of variance in skull shape
      throughout most of postnatal growth results from a balance between processes
      generating and removing variation, we compare covariance structures from age to
      age in two rodent species, cotton rats (Sigmodon fulviventer) and house mice (Mus
      musculus domesticus). We assess the overall similarity of covariance matrices by
      the matrix correlation, and compare the structures of covariance matrices using
      common subspace analysis, a method related to common principal components (PCs)
      analysis but suited to cases in which variation is so nearly spherical that PCs
      are ambiguous. We find significant differences from age to age in covariance
      structure and the more effectively canalized ones tend to be least stable in
      covariance structure. We find no evidence that canalization gradually and
      preferentially removes deviations arising early in development as we might expect
      if canalization results from compensatory differential growth. Our results
      suggest that (co)variation patterns are continually restructured by processes
      that equilibrate variance, and thus that canalization plays a critical role in
      molding patterns of integration.

PMID- 16409383
TI  - The brachymorph mouse and the developmental-genetic basis for canalization and
      morphological integration.
AB  - Although it is well known that many mutations influence phenotypic variability as
      well as the mean, the underlying mechanisms for variability effects are very
      poorly understood. The brachymorph (bm) phenotype results from an autosomal
      recessive mutation in the phosphoadenosine-phosphosulfate synthetase 2 gene
      (Papps2). A major cranial manifestation is a dramatic reduction in the growth of
      the chondrocranium which results from undersulfation of glycosaminoglycans (GAGs)
      in the cartilage matrix. We found that this reduction in the growth of the
      chondrocranium is associated with an altered pattern of craniofacial shape
      variation, a significant increase in phenotypic variance and a dramatic increase
      in morphological integration for craniofacial shape. Both effects are largest in
      the basicranium. The altered variation pattern indicates that the mutation
      produces developmental influences on shape that are not present in the wildtype.
      As the mutation dramatically reduces sulfation of GAGs, we infer that this
      influence is variation among individuals in the degree of sulfation, or variable
      expressivity of the mutation. This variation may be because of genetic variation
      at other loci that influence sulfation, environmental effects, or intrinsic
      effects. We infer that chondrocranial development exhibits greater sensitivity to
      variation in the sulfation of chondroitin sulfate when the degree of sulfation is
      low. At normal levels, sulfation probably contributes minimally to phenotypic
      variation. This case illustrates canalization in a particular developmental
      genetic context.

PMID- 16409384
TI  - Developmental origin of shark electrosensory organs.
AB  - Vertebrates have evolved electrosensory receptors that detect electrical stimuli
      on the surface of the skin and transmit them somatotopically to the brain. In
      chondrichthyans, the electrosensory system is composed of a cephalic network of
      ampullary organs, known as the ampullae of Lorenzini, that can detect extremely
      weak electric fields during hunting and navigation. Each ampullary organ consists
      of a gel-filled epidermal pit containing sensory hair cells, and synaptic
      connections with primary afferent neurons at the base of the pit that facilitate
      detection of voltage gradients over large regions of the body. The developmental
      origin of electroreceptors and the mechanisms that determine their spatial
      arrangement in the vertebrate head are not well understood. We have analyzed
      electroreceptor development in the lesser spotted catshark (Scyliorhinus
      canicula) and show that Sox8 and HNK1, two markers of the neural crest lineage,
      selectively mark sensory cells in ampullary organs. This represents the first
      evidence that the neural crest gives rise to electrosensory cells. We also show
      that pathfinding by cephalic mechanosensory and electrosensory axons follows the
      expression pattern of EphA4, a well-known guidance cue for axons and neural crest
      cells in osteichthyans. Expression of EphrinB2, which encodes a ligand for EphA4,
      marks the positions at which ampullary placodes are initiated in the epidermis,
      and EphA4 is expressed in surrounding mesenchyme. These results suggest that Eph
      Ephrin signaling may establish an early molecular map for neural crest migration,
      axon guidance and placodal morphogenesis during development of the shark
      electrosensory system.

PMID- 16409385
TI  - Pleiotropic mutation, modularity and evolvability.
AB  - The relationship between pleiotropy and the rate of evolution of a phenotypic
      character (evolvability) in a population is explored using computer simulations.
      I present results that suggest the rate of evolution of a phenotypic character
      may not decline when that character is pleiotropically associated to an
      increasing number of other characters, provided that the characters are under
      pure directional selection such that they are far from their optima relative to
      the average magnitude of a mutation. These conditions may be relevant during
      adaptive radiations. Adding pleiotropic associations to a set of characters in
      which one is under directional selection and the other is under stabilizing
      selection increases the rate of adaptation of the character under directional
      selection provided that the new characters that come to be pleiotropically
      associated are under directional selection. Thus, increasing the number of
      pleiotropic associations under these conditions increases the rate of adaptation
      of a character.

PMID- 16409386
TI  - Modularity and sense organs in the blind cavefish, Astyanax mexicanus.
AB  - Mexican tetra (Astyanax mexicanus) exist as two morphs: a sighted (surface) form
      and a blind (cavefish) form. In the cavefish, some modules are lost, such as the
      eye and pigment modules, whereas others are expanded, such as the taste bud and
      cranial neuromast modules. We suggest that modularity can be viewed as being
      nested in a manner similar to Bauplane so that modules express unique sets of
      genes, cells, and processes. In terms of evolution, we conclude that natural
      selection can act on any of these hierarchical levels within modules or on all
      the sensory modules as a whole. We discuss interactions within and between
      modules with reference to the blind cavefish from both genetic and developmental
      perspectives. The cavefish represents an illuminating example of module
      interaction, uncoupling of modules, and module expansion.

PMID- 16409390
TI  - Artificial organs begins 30th year of publication.

PMID- 16409391
TI  - Thirty years ago for artificial organs.

PMID- 16409387
TI  - Generality of vertebrate developmental patterns: evidence for a dermomyotome in
      fish.
AB  - The somitic compartment that gives rise to trunk muscle and dermis in amniotes is
      an epithelial sheet on the external surface of the somite, and is known as the
      dermomyotome. However, despite its central role in the development of the trunk
      and limbs, the evolutionary history of the dermomyotome and its role in
      nonamniotes is poorly understood. We have tested whether a tissue with the
      morphological and molecular characteristics of a dermomyotome exists in
      nonamniotes. We show that representatives of the agnathans and of all major
      clades of gnathostomes each have a layer of cells on the surface of the somite,
      external to the embryonic myotome. These external cells do not show any signs of
      terminal myogenic or dermogenic differentiation. Moreover, in the embryos of bony
      fishes as diverse as sturgeons (Chondrostei) and zebrafish (Teleostei) this layer
      of cells expresses the pax3 and pax7 genes that mark myogenic precursors. Some of
      the pax7-expressing cells also express the differentiation-promoting myogenic
      regulatory factor Myogenin and appear to enter into the myotome. We therefore
      suggest that the dermomyotome is an ancient and conserved structure that evolved
      prior to the last common ancestor of all vertebrates. The identification of a
      dermomyotome in fish makes it possible to apply the powerful cellular and genetic
      approaches available in zebrafish to the understanding of this key developmental
      structure.

PMID- 16409392
TI  - Uniformity of the fluid flow velocities within hollow fiber membranes of blood
      oxygenation devices.
AB  - A finite volume-based computational model was developed to investigate the
      uniformity of the fluid flow across the hollow fiber membranes in blood
      oxygenation devices. A two-dimensional annular cross section of a blood
      oxygenation device including about 3,300 hollow fiber membranes was used in the
      computation model. The equations governing the steady incompressible laminar flow
      in the blood oxygenation device were solved numerically and the results were
      compared with those obtained from the equivalent porous medium approximation. For
      the porous medium approximation, the Ergun equation was used for evaluating the
      permeability. The simulation results showed that the fluid molecules spend about
      six times longer in the fiber bundle region than that in its equivalent porous
      medium approximation model. The computational model also provides a more detailed
      fluid flow pattern in the membrane compartment of the blood oxygenator.

PMID- 16409393
TI  - Estimation of mechanical heart valve cavitation in an electro-hydraulic total
      artificial heart.
AB  - The purpose of this study was to establish a method for estimating mechanical in
      vitro heart valve cavitation in an electro-hydraulic total artificial heart
      (EHTAH). The variations in the left driving pressure (LDP) slope of the EHTAH
      were used as an index of the cavitation intensity. The LDP slope was controlled
      by changing the stroke volume of the EHTAH. The stroke volume was changed from
      full-filling and full-eject to partial-filling and partial-eject conditions. A 25
      mm Medtronic Hall valve was installed in the mitral position of the EHTAH.
      Cavitation bubbles were concentrated on the valve stop; the major cause of these
      cavitation bubbles was determined to be squeeze flow. The valve-closing velocity
      was found to be proportional to increases in the LDP slope and the stroke volume
      of the left blood pump. The cavitation intensity and the cavitation event rate
      increased with increases in the stroke volume of the EHTAH. A consistent
      correlation was observed between the valve-closing velocity and the cavitation
      intensity. The LDP slope of the EHTAH may play an important role in estimating
      the mechanical heart valve cavitation intensity.

PMID- 16409394
TI  - Out-of-center extracorporeal membrane oxygenation for adult cardiogenic shock
      patients.
AB  - Patients with cardiogenic shock refractory to conventional management require
      advanced mechanical circulatory support such as extracorporeal membrane
      oxygenation (ECMO). In hospitals lacking ECMO facilities, interhospital
      transportation is necessary for further patient management. Thirty-one adult
      cardiac patients, who were transported to our hospital by our ECMO transport team
      between January 1998 and July 2004, were enrolled in this study. The median
      transportation distance was 200 km (range: 3-300 km). During transportation, the
      ECMO circuit per se and the patients did not have complications. Of the 31
      patients, 20 (64.2%) were weaned off ECMO or bridged to ventricular assist
      devices and 10 patients (32.1%) survived to discharge. Delayed transfer (>2 days)
      and high organ dysfunction score were associated with poor outcomes. The survival
      rate was similar to that of our in-hospital group (survival rate: 32.8%, n = 64).
      In conclusion, adult cardiogenic shock patients requiring interhospital ECMO
      transport had a reasonable chance of survival.

PMID- 16409395
TI  - Is skeletal muscle ventricle chronic stability dependent on wall stress? Design
      implications.
AB  - Chronic skeletal muscle ventricle (SMV) stability is essential for clinical
      implementation. SMVs in animal models have chronically expanded or collapsed when
      exposed to physiologic pressures. SMV wall stress is a more appropriate indicator
      than pressure or geometry to compare SMVs between studies. SMV wall tensions
      during conditioning were determined for SMVs that collapsed, expanded, or were
      isovolumetric in a previous study. Wall stresses in SMVs that expanded (2.76 +/-
      0.803 N/cm(2)) were significantly greater than isovolumetric SMVs (0.89 +/-
      0.450) and SMVs that collapsed (0.88 +/- 0.451). These data support the existence
      of minimum and maximum wall stresses for SMV volume stability and provide empiric
      estimates for SMV design. Scaling SMV designs from animal models with smaller
      volumes and similar pressures may result in greater wall stresses in clinical
      designs. Therefore, the use of volume limiting implants or an isovolumetric
      conditioning phase to increase the wall stress expansion threshold may be
      required.

PMID- 16409396
TI  - Poly (epsilon-caprolactone) grafted with nano-structured chitosan enhances growth
      of human dermal fibroblasts.
AB  - Polyester films are modified with their bioactivity for tissue engineering by
      grafting a nano-structured bioactive material, nano-structured chitosan (nano
      CS), on a model polymer, poly (epsilon-caprolactone) (PCL). The nano-CS was
      duplicated using a solvent-etched PCL mold and then grafted onto PCL using a
      selected solvent. The structure of the nano-CS/PCL surface was characterized
      using an atomic force microscope to observe the topography and determine the
      roughness. The centerline average roughness, Ra, of the surface of the nano
      CS/PCL film is 106.0+/-4.0 nm whereas that of the surface of the CS-grafted PCL
      film (CS/PCL) is 3.6+/-0.4 nm. The latter is therefore very smooth. CS is known
      to swell following hydration, so the Ra values were determined again after
      immersion for 12 h in phosphate buffered saline. Although the centerline average
      roughness of the nano-CS/PCL was lower, it still markedly exceeded that of the
      CS/PCL film. Cells grown on nano-CS/PCL, CS/PCL, nano-structured PCL (nano-PCL),
      and PCL films were observed by fluorescent staining and analyzed by MTT (3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) viability assay following
      3 and 7 days of culture, to evaluate the effects of the design on the growth of
      fibroblasts. The viability assay of the cells reveals that the growth rate of
      cells on both CS/PCL and nano-CS/PCL films significantly exceeds (P<0.001) those
      of PCL and nano-PCL films on both cultural days. Additionally, the growth rate
      and proliferation of fibroblasts on nano-CS/PCL films significantly exceed
      (P<0.001) those on CS/PCL films after both periods of culturing, suggesting that
      the bioactive surface following a nano-structured treatment promotes the growth
      rate of cells. However, nano-PCL films do not have the same effects as nano
      CS/PCL films do. In conclusion, a novel biomaterial, nano-CS/PCL, is developed by
      grafting a nano-structured bioactive surface, CS, onto the PCL surface to promote
      the the growth rate of fibroblasts. This work elucidates a new concept for
      designing films or scaffolds for tissue engineering-the grafting of nano
      structured bioactive biomaterials to the films or scaffolds to promote the growth
      of cells.

PMID- 16409397
TI  - Evaluation of biodegradable polyesters modified by type II collagen and Arg-Gly
      Asp as tissue engineering scaffolding materials for cartilage regeneration.
AB  - Synthetic biodegradable polyesters poly(L-lactide) (PLLA) and poly(D,L-lactide
      coglycolide) (PLGA) (50:50) modified by porcine type II collagen and an Arg-Gly
      Asp (RGD)-containing protein were evaluated as scaffolds for cartilage
      regeneration in this study. Cytocompatibility of the polymer films was tested
      using immortalized chondrocytes. Neocartilage formation in vitro on cell-seeded
      scaffolds was further examined using primary porcine chondrocytes. The
      inflammatory response of the scaffolds was evaluated subcutaneously in rats. A
      pilot animal study was conducted, in which rabbit allogeneic chondrocyte-seeded
      scaffolds were implanted to repair the defected rabbit knee cartilage. The
      results demonstrated that PLGA as well as its blends with PLLA had better cell
      growth than pure PLLA, and that type II collagen enhanced, but RGD inhibited cell
      proliferation. Scaffolds made of blended PLLA/PLGA had larger dynamic compressive
      modulus compared to scaffolds made of PLLA or PLGA single polymer. Chondrocyte
      seeded scaffolds modified by type II collagen without RGD had the greater number
      of cells as well as higher glycosaminoglycan (GAG) and collagen contents compared
      to scaffolds without type II collagen modification or scaffolds further modified
      with RDG. Type II collagen modification prevented infiltration by host tissue and
      capsule formation. Unmodified PLLA and PLLA/PLGA constructs demonstrated
      persisting inflammatory response after 6 months, while all type II collagen
      modified PLLA/PLGA constructs showed complete repair and no inflammation. Partial
      or full repair was observed after 2 months of postimplantation in type II
      collagen-modified PLLA/PLGA constructs, with equal cellularity and 75-80% matrix
      contents of a normal rabbit articular cartilage. It was concluded that PLLA/PLGA
      blended scaffolds modified by type II collagen were a potential tissue
      engineering scaffold for cartilage regeneration.

PMID- 16409398
TI  - Improvement of metabolic and cardiorespiratory responses through treadmill gait
      training with neuromuscular electrical stimulation in quadriplegic subjects.
AB  - This work assessed the influence of treadmill gait training with neuromuscular
      electrical stimulation (NMES) on the metabolic and cardiorespiratory responses in
      quadriplegic subjects. The gait group (GG) (n=11) performed 6 months of treadmill
      training with 30-50% body weight support and with the help of physiotherapists,
      twice a week, allotting 20 min for each session. The control group (CG) (n=10),
      during the 6 months of training, did not perform any activity using NMES,
      performing instead conventional physiotherapy. Metabolic and cardiorespiratory
      responses (O(2) uptake [VO(2)], CO(2) production [VCO(2)], pulmonary ventilation
      (V(E)), heart rate [HR], and blood pressure [BP]) were measured on inclusion and
      after 6 months. For the GG, differences were found in all parameters after
      training (P<0.05), except for HR and diastolic BP. During gait, VO(2) (L/min)
      increased by 36%, VCO(2) (L/min) increased by 42.97%, V(E) (L/min) increased by
      30.48%, and systolic BP (mm Hg) increased by 4.8%. For the CG, only VO(2) and
      VCO(2) (L/min) significantly increased at rest (30.82 and 16.39%, respectively)
      and during knee-extension exercise (26.29 and 17.37%, respectively). Treadmill
      gait with NMES was, therefore, more efficient toward increasing the aerobic
      capacity due to yielding higher metabolic and cardiovascular stresses.

PMID- 16409399
TI  - Continuous venovenous renal replacement therapy with a pulsatile tubular blood
      pump: analysis of efficacy parameters.
AB  - A three-valve pulsatile tubular pump was used in 10 pigs weighing 9.9+/-0.3 kg,
      connected to a neonatal hemofiltration (HF) circuit to analyze the parameters to
      determine the ultrafiltration effectiveness for venovenous continuous renal
      replacement therapy. Forty 30-min periods were studied to analyze the influence
      of the catheter diameter, purification technique (HF or hemodiafiltration), pump
      pulsation frequency, percentage time in diastole, percentage time in diastole in
      which the post pump valve was closed, and percentage time in systole in which the
      post filter valve was closed, on ultrafiltrate volume and blood flow through the
      filter. A higher ultrafiltrate flow was achieved with a frequency of 60 bpm than
      with 30 bpm, a diastolic time of 65% of the total cycle versus 50%, and a blood
      flow of greater than 20 mL/min versus less than 20 mL/min. The ultrafiltrate flow
      increases in relation to the blood flow, the frequency of the pump, and the
      diastolic time.

PMID- 16409400
TI  - The pivot wash in two impeller modes for the Baylor/Miwatec centrifugal blood
      pump.
AB  - A centrifugal blood pump with a double pivot impeller and an eccentric inlet port
      is being developed as an implantable artificial heart by the Baylor College of
      Medicine and Miwatec Co. Ltd. Flow visualization measurements were conducted to
      compare the flow around the pivot for two impeller operational modes: the top and
      the bottom contact modes. In the top contact mode, one-way flow in the pivot gap
      due to the eccentric vortex was observed, and sufficient wall shear rate to
      prevent thrombus formation was attained around the bottom pivot for over 1,400
      rpm. Computational fluid dynamic analyses confirmed that the causes of the
      eccentric vortex were the inlet eccentricity and the pressure imbalance in the
      volute.

PMID- 16409401
TI  - The possibility of a veno-arterial bypass system using the Abiomed BVS 5000.
AB  - Effect of Abiomed BVS 5000 (Cardiovascular Inc., Danvers, MA, U.S.A) has been
      reported for mechanical assist circulation in cardiogenic shock. However, this
      pump is generally used as a ventricular assist device, not as a device for veno
      arterial bypass. Therefore, we evaluated its effectiveness through an experiment.
      The left anterior descending branch of pigs' heart was ligated to prepare a model
      of acute myocardial infarction, and after the onset of cardiogenic shock,
      circulation was initially supported for 30 min using the BVS 5000, followed by
      support for another 30 min using a Gyro pump (Gyro, Kyocera, Inc., Kyoto, Japan).
      Subsequently, circulation was additionally supported for 30 min using both a Gyro
      and an intra-aortic balloon pump (IABP) (Tokai Medical Inc., Aichi, Japan) (Gyro
      + IABP). Circulation was supported in each group at 30-min intervals in the
      reversed order of assisted circulation. Although the mean aortic pressure, pump
      flow, and total flow were not significantly different among the three setups, the
      pulse pressure was 48.2 +/- 3.3, 12.2 +/- 2.2, and 29.9 +/- 3.8 mm Hg in Abiomed,
      Gyro, and Gyro + IABP, respectively. Although neither coronary arterial nor
      myocardial blood flow showed significant differences among the three setups, the
      renal arterial blood flow was significantly larger in BVS 5000 compared to the
      other two setups. In this study, we selected an alpha-cube (Platium Cube NCVC
      6000, Edwards Research Medical Inc., Salt Lake City, UT, U.S.A.), which is
      considered as an oxygenator that produces minimum pressure loss. Therefore, the
      pulsatile flow we obtained with the Abiomed was maintained even after we started
      using the oxygenator. The pulsatile flow had positive effects on renal
      circulation and peripheral circulation.

PMID- 16409403
TI  - Comparison of the role of the subcutaneous tissues in cutaneous wound healing in
      the dog and cat.
AB  - OBJECTIVE: To describe and compare the contribution of the subcutaneous tissues
      to 1st and 2nd intention cutaneous wound healing in the dog and cat. STUDY
      DESIGN: Experimental study. ANIMALS: Domestic shorthaired cats (n=6) and 6 beagle
      dogs. METHODS: Paired wounds were created on either side of the dorsal midline;
      the subcutaneous tissue was removed on 1 side and left intact on the other.
      Square, open wounds of the dorsal aspect of the thorax were observed for 21 days
      to monitor granulation tissue formation, wound contraction, epithelialization,
      and total healing (contraction+epithelialization). Breaking strength of sutured
      linear wounds was measured 7 days after wounding. Laser-Doppler perfusion imaging
      (LDPI) was used to measure cutaneous perfusion. RESULTS: First intention healing:
      subcutaneous tissue removal had no consistent effect on sutured wound strength at
      7 days in dogs or cats. Second intention healing: removal of subcutaneous tissue
      reduced wound perfusion, granulation, contraction, epithelialization, and total
      healing. Granulation tissue formation and wound contraction were delayed to a
      significantly greater degree in cats than in dogs (P<.05). Two dogs (33%) had
      minor wound infections. CONCLUSIONS: The subcutaneous tissues make an important
      contribution to 2nd intention cutaneous healing. Dog and cat wounds had delayed
      2nd intention healing when subcutaneous tissues were removed; wounds in dogs, but
      not cats, had largely recovered from this delay by 21 days. CLINICAL RELEVANCE:
      Extensive debridement of subcutaneous tissue may delay wound healing particularly
      in feline patients. A higher risk for wound infections may accompany extensive
      removal of subcutaneous tissues in dogs.

PMID- 16409404
TI  - Biomechanical Analysis of Unilateral External Skeletal Fixators Combined with IM
      Pin and Without IM-Pin Using Finite-Element Method.
AB  - OBJECTIVES: To determine if a unilateral external skeletal fixator (ESF) with a
      carbon fiber connecting rod (IMEX SK) without an intramedullary (IM)-pin is
      mechanically comparable with a unilateral ESF with a stainless-steel connecting
      rod (IMEX KE) with an IM-pin. STUDY DESIGN: Finite-element method (FEM)-computer
      simulation. METHODS: FEM models were validated by comparison against data from
      mechanical testing. Three-dimensional FEM models of a femur with a mid-diaphyseal
      fracture with a 20 mm gap were developed with 4 unilateral external skeletal
      fixator devices (6-pin KE, 6-pin KE IM-pin, 6-pin SK, and 6-pin SK IM-pin). A 300
      N load was applied to the femur at the proximal end in a direction of theta = 10
      degrees distally and phi = 10 degrees laterally cranially. Relative displacements
      in x-, y- and z-directions at the gap were obtained and the overall stiffness was
      calculated as 300 N/total displacement. Load transfer at the pin-bone interface
      (PBI) was assessed by determining the von Mises stress maxima at the PBI-related
      nodes. RESULTS: The 6-pin SK had superior mechanical performance compared with
      the 6-pin KE by exhibiting smaller displacements in all directions and higher
      stiffness. Compared with the 6-pin KE IM-pin, the 6-pin SK (without IM-pin) was
      superior in craniocaudal and lateromedial displacements, but inferior in axial
      displacements, overall stiffness and von Mises stress maxima. The 6-pin SK IM-pin
      was superior to the 6-pin KE IM-pin based on smaller displacements and higher
      stiffness. CONCLUSIONS: Although the SK device had superior mechanical
      performance compared with a KE device in a unilateral configuration, the addition
      of an IM-pin continues to be a powerful method of enhancing mechanical
      performance of either IMEX SK or IMEX KE unilateral constructs in clinical cases.
      CLINICAL RELEVANCE: Based on the results of this FEM study we recommend the use
      of the "tied-in" IM-pin with the ESF clinically when striving for high rigidity.
      In less challenging situations, a unilateral SK ESF without IM-pin might provide
      sufficient rigidity for a successful fracture repair.

PMID- 16409405
TI  - Computed tomographic evaluation of canine radioulnar incongruence in vivo.
AB  - OBJECTIVE: To compare radioulnar incongruence (RUI) of normal canine elbows and
      elbows with arthroscopically confirmed medial compartment disease in vivo using
      systematic computed tomography (CT) measurements. STUDY DESIGN: Prospective
      comparison of RUI measurements in normal and dysplastic canine elbows. SAMPLE
      POPULATION: Right elbows of 25 medium-large breed, adult dogs with medial
      compartment disease and 9 medium-large breed, adult dogs with no elbow disease.
      METHODS: Transverse CT images of proximal radioulnar articulation were
      reformatted to dorsal and sagittal planes. RUI in 3 locations of the forelimb's
      medial coronoid was measured. Arthroscopy confirmed diagnosis of medial
      compartment disease in the diseased group. RUI measurements of the diseased and
      normal elbows were compared. RESULTS: Cumulative statistical analysis of RUI in
      all planes revealed no significant difference between the normal and abnormal
      elbows (P = .61). The abnormal elbows had negative mean RUI at the mid (P = .56)
      and cranial (P = .24) coronoid regions that were not significantly different from
      normal elbows and mean positive RUI at the base coronoid that was significantly
      greater than in normal elbows (P = .00082). CONCLUSION: Canine elbows with
      established medial compartment disease do not have significant RUI at the medial
      coronoid region at the time of diagnosis when compared with normal elbows.
      CLINICAL RELEVANCE: If RUI is a significant factor in the pathophysiology of
      medial compartment elbow disease in the dog, it does not appear to be present at
      the time of diagnosis of disease. Ulnar or radial osteotomies do not appear to be
      indicated for restoration of normal radioulnar articular surface alignment.

PMID- 16409406
TI  - Synovial cysts associated with cauda equina syndrome in two dogs.
AB  - OBJECTIVE: To report synovial cysts associated with cauda equina syndrome in 2
      dogs. STUDY DESIGN: Clinical cases. ANIMALS: Two German Shepherd dogs. METHODS:
      After magnetic resonance imaging detection, cysts were surgically removed via
      dorsal laminectomy. RESULTS: Six and 8 months after surgery, both dogs were free
      of clinical signs and no pain was elicited on lumbosacral joint manipulation.
      CONCLUSION: Although described in dogs, cysts at the lumbosacral joint might
      cause compression of the cauda equina nerve roots. Radical excision of the cyst
      capsule can result in resolution of clinical signs. CLINICAL RELEVANCE: Synovial
      cysts should be considered in the differential diagnosis of dogs with cauda
      equina compression syndrome when lumbosacral degenerative joint disease is
      present.

PMID- 16409408
TI  - Buried tension sutures: force-tension comparisons of pulley, double butterfly,
      mattress, and simple interrupted suture patterns.
AB  - OBJECTIVES: To compare suture patterns (simple interrupted, modified pulley,
      horizontal mattress, double butterfly) by use of a novel in vitro model that
      quantifies force required for closure against tension. STUDY DESIGN: In vitro
      study. SAMPLE POPULATION: Suture constructs. METHODS: An in vitro suturing frame
      was constructed with extension springs to provide a standard resistance against
      movement of 2 panels of loops toward each other. Four different suture patterns
      were applied to the frame in randomized trials. The frame was affixed to a
      tensiometer that measured the force required for each suture pattern to close a
      fixed distance (3.81 cm) at a constant rate (5.08 cm/min) against the tension
      (0.6 kg/cm) of the extension springs. The closure distance and tension were
      selected subjectively to mimic tension encountered clinically during wound
      reconstruction oncologic surgical procedures. RESULTS: The modified pulley suture
      required the least force to close, followed by the double butterfly, simple
      interrupted, and horizontal mattress patterns. CONCLUSIONS: The modified pulley
      suture and double butterfly suture patterns require less force to close a given
      distance under tension than either simple interrupted or horizontal mattress
      suture patterns. CLINICAL RELEVANCE: Application of tension relieving suture
      techniques for fascia, subcutaneous, and buried-knot subdermal suturing should be
      considered to facilitate direct closure of wounds under tension. Modified pulley
      and double butterfly suture patterns offer some mechanical advantage by requiring
      less force to achieve closure compared with other suture patterns that might be
      used in reconstructive surgery.

PMID- 16409407
TI  - The effects of epidural deracoxib on the ground reaction forces in an acute
      stifle synovitis model.
AB  - OBJECTIVE: To evaluate the efficacy of epidurally administered deracoxib to
      mediate the signs of a sodium urate crystal-induced stifle synovitis in dogs, and
      to compare the efficacy of epidural versus subcutaneously administered deracoxib.
      STUDY DESIGN: Experimental, randomized, blinded, placebo-controlled modified
      cross-over design. ANIMALS: Random source, adult, mixed breed dogs (n = 24; 14
      males, 10 females). METHODS: Sodium urate crystals were used to create a stifle
      synovitis model to evaluate the efficacy of deracoxib. Dogs were divided into 4
      groups: 3 mg/kg epidural deracoxib, 1.5 mg/kg epidural deracoxib, 3 mg/kg
      subcutaneous deracoxib, and a placebo (vehicle for deracoxib). Force plate and
      subjective evaluations were made at time 0, 2, 4, 8, 12, and 24 hours post
      treatment. Repeated measures ANOVA with Bonferroni-corrected post hoc comparisons
      was used to determine significant treatment effects. RESULTS: Peak vertical force
      (PVF) and vertical impulse (VI) were both significantly higher in deracoxib
      treated dogs compared with placebo. For 3 mg/kg epidural and subcutaneous
      deracoxib, PVF and VI were significantly greater than for 1.5 mg/kg epidural
      deracoxib. Overall pain score for all deracoxib-treated dogs was significantly
      lower than for placebo dogs. CONCLUSIONS: Epidural administration of deracoxib is
      effective at providing analgesia in an acute joint pain model; however, it does
      not appear to be more effective than systemic administration. CLINICAL RELEVANCE:
      Injectable deracoxib is effective in providing analgesia in acute inflammatory
      conditions of synovial joints.

PMID- 16409409
TI  - In vitro comparison of two techniques for suture prosthesis placement in the
      muscular process of the equine arytenoid cartilage.
AB  - OBJECTIVE: To compare in vitro the load necessary for a partial and complete
      rupture of the muscular process arytenoid cartilage when a suture prosthesis is
      positioned by a bone trocar versus a trocar point needle and to compare failure
      mode. STUDY DESIGN: Experimental using cadaver specimens. SAMPLE POPULATION:
      Larynges from 18 Thoroughbred race horses, aged 2-20 years. METHODS: Arytenoid
      cartilages were separated randomly into 2 groups: group 1-suture prosthesis
      inserted directly through the muscular process using a curved trocar point needle
      and group 2-suture passed through a hole predrilled with a 3 mm bone trocar.
      Distracting force (constant rate, 1 mm/s) was applied to the suture until failure
      of the muscular process. Partial failure load, maximum load at complete failure,
      and force-time curve were recorded. Each arytenoid cartilage was examined,
      radiographed, and classified as having a linear or curved failure plane. RESULTS:
      No significant differences in mechanical test variables were detected. Failure
      mode followed the fissures occurring at the beginning of failure and then
      followed the tension axis. Significantly more linear failures occurred in group 2
      (trocar) and more curved failures occurred in group 1 (needle). CONCLUSION: Use
      of a bone trocar for tunneling through the muscular process may reduce fissure
      formation. CLINICAL RELEVANCE: Use of bone trocar to create a hole in the
      muscular process of the arytenoid cartilage for suture passage in laryngoplasty
      may reduce fissure formation and decrease the risk of cartilage failure from
      suture pullout.

PMID- 16409410
TI  - A mechanical study of ligature security of commercially available pre-tied
      ligatures versus hand tied ligatures for use in equine laparoscopy.
AB  - OBJECTIVE: To determine a hand-tied ligature knot configuration, suture size, and
      suture type that would be an acceptable substitute to commercially available
      ligature knots for use in equine laparoscopic surgery. STUDY DESIGN: Three-factor
      ANOVA with the fixed effects being suture type, suture size, and knot type. The
      dependent variable was ligature security (load to failure). METHODS: Commercially
      available Endoloop and 4 hand-tied slipknot ligatures were compared with a 4
      layer square knot. The hand tied ligature knots tested were the 4S modified
      Roeder knot, the Brooks knot, the modified Roeder knot, and the Weston knot. Two
      suture sizes (0, 2) of each of 2 suture types (polydioxanone, polyglactin 910)
      were tested with each hand tied knot. Two types (polydioxanone, polyglactin 910)
      of size 0 Endoloop were tested. Twenty repetitions of each knot suture type were
      tested for force to yield on a materials testing machine. Statistical analysis
      consisted of a 3-way ANOVA with individual comparisons made using the Bonferroni
      method. Significance was P< or = .05. RESULTS: Only the 4S modified Roeder knot
      in 2 polydioxanone (103 N) was comparable with the breaking strength of the
      square knots (157 N). All other knot suture combinations tested were
      significantly weaker than the square knot (range, 2-18 N). CONCLUSION: For equine
      laparoscopy, a 2 polydioxanone 4S modified Roeder knot would be an acceptable
      alternative to the commercially available Endoloop. CLINICAL RELEVANCE:
      Laparoscopic slip knots are commonly used in equine laparoscopic surgery. Various
      knot configuration and suture size and type combinations will affect the security
      of the slip knot.

PMID- 16409411
TI  - Intravenous continuous infusion of lidocaine for treatment of equine ileus.
AB  - OBJECTIVE: To determine if intravenous lidocaine is useful and safe as a
      treatment for equine ileus. STUDY DESIGN: Prospective double-blinded placebo
      controlled trial. STUDY POPULATION: Horses (n = 32) with a diagnosis of
      postoperative ileus (POI) or enteritis and that had refluxed >20 L or had been
      refluxing for >24 hours. METHODS: Refluxing horses were administered lidocaine
      (1.3 mg/kg intravenously [IV] as a bolus followed by a 0.05 mg/kg/min infusion)
      or saline (0.9% NaCl) solution placebo for 24 hours. Variables evaluated included
      volume and duration of reflux, time to 1st fecal passage, signs of pain,
      analgesic use, heart rate and arrhythmias, respiratory rate, temperature, days of
      hospitalization, outcome (survival to discharge), and complications. RESULTS: Of
      the lidocaine-treated horses, 65% (11/17) stopped refluxing within 30 hours
      (mean+/-SD, 15.2+/-2.4 hours) whereas 27% (4/15) of the saline-treated horses
      stopped within 30 hours. Fecal passage was significantly correlated with response
      to treatment; horses that responded to lidocaine passed feces within 16 hours of
      starting the infusion. Compared with placebo treatment, lidocaine treatment
      resulted in shorter hospitalization time for survivors, equivalent survival to
      discharge, no clinically significant changes in physical or laboratory variables,
      and no difference in the rate of incisional infections, jugular thrombosis,
      laminitis, or diarrhea. Muscle fasciculations occurred in 3 lidocaine-treated
      horses (18%). CONCLUSION: IV lidocaine significantly improved the clinical course
      in refluxing horses with minimal side effects. CLINICAL RELEVANCE: At the
      infusion rate studied, IV lidocaine is safe and should be considered for the
      treatment of equine ileus.

PMID- 16409412
TI  - Principles of uniapical and biapical radial deformity correction using dome
      osteotomies and the center of rotation of angulation methodology in dogs.
AB  - OBJECTIVE: To describe the normal anatomic axis of the canine radius in 2 planes
      (frontal, sagittal), and report the use and efficacy of dome osteotomies for
      acute correction of canine antebrachial deformities. STUDY DESIGN: Retrospective
      study. SAMPLE POPULATION: Normal antebrachii (n = 20) radiographs were used as a
      reference, and 7 dogs with 9 radial angular limb deformities that were corrected
      by use of dome osteotomies. METHODS: Orthogonal radiographs of 20 normal
      antebrachii were used to determine normal ranges of frontal (FPA) and sagittal
      plane anatomic axes (SPA). Pre and postoperative radiographs of 7 dogs (9 radii)
      that had surgical correction of radial angular limb deformities by dome
      osteotomies were reviewed. Success at deformity correction into established
      normal ranges and to the normal contralateral side, if present, was determined.
      RESULTS: Normal ranges were FPA, 0-8 degrees and SPA, 8-35 degrees . There were 4
      biapical and 5 uniapical deformities. FPA and SPA were corrected into normal
      range in 66% and 78% of affected limbs, respectively; however, only 44% of radii
      were corrected into normal ranges in both planes. CONCLUSIONS: Ranges for normal
      canine radial axes can be used as goals for angular limb correction when there is
      bilateral angular deformity. The dome osteotomy technique is advantageous in
      certain conditions for biplanar deformity correction. CLINICAL RELEVANCE: Dome
      osteotomies can be used to correct radial deformities in the frontal and sagittal
      planes, with certain advantages, but are heavily reliant on appropriate
      preoperative planning.

PMID- 16409413
TI  - Vertical patellar position in large-breed dogs with clinically normal stifles and
      large-breed dogs with medial patellar luxation.
AB  - OBJECTIVE: To further define vertical patellar position, as measured by the ratio
      of patellar ligament length to patellar length (L:P), in large-breed dogs with
      clinically normal stifles and compare that to the L:P of large-breed dogs with
      medial patellar luxation (MPL). STUDY DESIGN: Retrospective study. SAMPLE
      POPULATION: Large-breed dogs (n = 50) with clinically normal stifle joints and 30
      large-breed dogs with MPL. METHODS: Large-breed dogs with clinically normal
      stifle joints or MPL were identified and divided into groups (NORM and MPL,
      respectively). L:P values were determined for each dog by 4 observers from single
      lateral stifle radiographs. L:P was compared between NORM and MPL groups and 95%
      confidence intervals (CIs) were calculated. RESULTS: All 4 observers found a
      significantly higher L:P (more proximally positioned patella) for the MPL group
      compared with the NORM group. Overall mean (+/-SEM) L:P were: NORM, 1.71+/-0.020
      and MPL, 1.87+/-0.025. The 95% CI was determined to be 1.45-1.97 for the NORM
      group and 1.57-2.17 for the MPL group. CONCLUSIONS: Large-breed dogs with MPL had
      a significantly more proximal vertical patellar position compared with large
      breed dogs with clinically normal stifles. Large-breed dogs with L:P values >1.97
      are considered to have patella alta. CLINICAL RELEVANCE: Proximal displacement of
      the patella within the femoral trochlear groove may play a role in MPL in large
      breed dogs.

PMID- 16409414
TI  - Accidental entrapment of an endo-bronchial blocker tip by a surgical stapler
      during selective ventilation for lung lobectomy in a dog.
AB  - OBJECTIVE: To describe the use of an endobronchial blocker (EBB) and to perform
      selective ventilation during pulmonary lobe resection via thoracotomy in a dog
      and report its accidental stapling in the resection site. STUDY DESIGN: Clinical
      case report. ANIMAL: One female dog with a suspected abscess or neoplasia of the
      right caudal pulmonary lobe. METHODS: One-lung ventilation was performed using a
      wire-guided EBB to seal the contaminated parenchyma and facilitate surgical
      access. The affected lung parenchyma was resected and the resection site was
      closed with staples. RESULTS: Lobar resection was performed successfully, but the
      loop of the EBB guide wire was inadvertently entrapped in the staple line of the
      lobectomy. Staples were removed to release the wire loop, and the resulting air
      leak caused loss of ventilation control until the parenchyma was re-sealed.
      CONCLUSIONS: We recommend removing the wire guide associate with the EBB after
      successful lung separation to avoid accidents that could have life-threatening
      consequences if not recognized. CLINICAL RELEVANCE: One-lung ventilation is
      useful to isolate healthy parenchyma from diseased parenchyma during lobectomy.
      Anesthesiologists and surgeons need to be aware of the potential complications
      associated with use of EBB.

PMID- 16409415
TI  - Evaluation of hemorrhage, sample size, and collateral damage for five hepatic
      biopsy methods in dogs.
AB  - OBJECTIVES: To compare the volume of hemorrhage, number of lobules, and portal
      triads available for histologic evaluation, and resultant collateral damage
      between 5 hepatic biopsy methods: biopsy punch, biopsy needle, ligature method,
      laparoscopic biopsy forceps, and ultrasonically activated scalpel (UAS). STUDY
      DESIGN: Experimental, repeated measures, block. ANIMALS: Twelve adult dogs.
      METHODS: Biopsies were obtained from the periphery and center of the left lateral
      liver lobe of each dog using each of 5 biopsy techniques. Hemorrhage was
      quantified and compared between methods and sites. Biopsy samples were evaluated
      histologically to characterize collateral damage and determine the number of
      lobules and portal triads sampled. RESULTS: Regardless of technique, liver biopsy
      resulted in minimal hemorrhage (<2 mL). For peripheral biopsies, UAS was
      comparable with the ligature method, but caused significantly less hemorrhage
      than all other methods, whereas for central biopsies, UAS caused significantly
      less hemorrhage than other methods. Except for the laparoscopic biopsy forceps,
      UAS caused significantly more collateral damage than other methods. UAS and
      ligature biopsy methods yielded specimens that had more portal triads per sample
      than other methods. Eight of 48 biopsy needle samples were inadequate for
      histologic evaluation, whereas other methods yielded adequate specimens.
      CONCLUSIONS: All biopsy methods produced minimal hemorrhage and except for needle
      biopsy yielded adequate tissue samples for histologic evaluation. CLINICAL
      RELEVANCE: Use of UAS is a reliable, safe alternative technique for liver biopsy
      and can be used laparoscopically to obtain large tissue samples.

PMID- 16409416
TI  - Use of scintigraphy for diagnosis of equine paranasal sinus disorders.
AB  - OBJECTIVES: To describe and analyze subjective and objective scintigraphic
      findings in horses with paranasal sinus disorders. ANIMALS: Horses with suspected
      disorders of the paranasal sinuses or cheek teeth (n = 48) and control horses (n
      = 30). METHODS: 99Technetium-methylenediphosphate (99Tc-MDP; 7500 MBq) was
      administered for scintigraphic examination of the skull. Abnormal patterns of
      increased radionuclide uptake (IRU) were identified and subjectively described.
      Scintigrams and radiographs were blindly assessed by 2 clinicians and the
      accuracy of the imaging modalities was compared. Objective analysis was performed
      by comparing regions of interest (ROI) drawn over areas of abnormal IRU to the
      equivalent area on the unaffected side using the Mann-Whitney test. An ROI ratio
      (affected:non-affected sides) was also calculated for each lesion. RESULTS:
      Twenty-eight horses were diagnosed with primary (15) or secondary (13) sinusitis.
      Nine primary sinusitis cases had focal area(s) of moderate or marked IRU in
      addition to a more diffuse uptake in the affected sinus(es). kappa was marginally
      higher for scintigraphic assessment of paranasal sinus disorders than for
      radiographic assessment. There were significant differences in mean counts/pixel
      in ROI drawn on the affected side compared with the non-affected side. There was
      considerable overlap between the magnitudes of ROI ratios found with many
      different disorders. CONCLUSIONS: Scintigraphy can be useful for differentiation
      of sinusitis of dental origin from other causes of sinusitis. Quantitative
      analysis of scintigrams is not reliable for identification of particular
      disorders. CLINICAL RELEVANCE: Focal areas of moderate or marked IRU may be
      observed with primary sinusitis. Careful 3-dimensional localization of the
      lesion, along with consideration of other clinical and diagnostic findings should
      be performed to prevent false-positive diagnoses of periapical infection in such
      instances.

PMID- 16409417
TI  - Beta-blockers for uncomplicated hypertension -- mugged by armchair scientists?

PMID- 16409418
TI  - 'Class effect' amongst cardiac drugs: term of convenience or pharmacological
      reality?

PMID- 16409419
TI  - Breast cancer surgery: not for the occasional operator.

PMID- 16409420
TI  - The current status of robotic and laparoscopic pyeloplasty.

PMID- 16409421
TI  - Role of robotics in the management of secondary ureteropelvic junction
      obstruction.
AB  - Patients with recurrent ureteropelvic junction obstruction (UPJO) present a
      treatment dilemma to urologists. Second-line therapies have previously been shown
      to fail at a higher rate than the initial therapeutic procedure. We report our
      experience with robotic-assisted, dismembered pyeloplasty in patients with
      secondary UPJO. Since November 2002, 44 robotic-assisted laparoscopic
      pyeloplasties (RALPs) have been performed at our institution. Of these, seven
      patients had undergone previous definitive treatment for UPJO. Anderson-Hynes
      dismembered pyeloplasty was the preferred reconstructive technique in all
      patients. The patients were divided into two groups: primary pyeloplasty patients
      (group 1) and secondary pyeloplasty patients (group 2). Variables examined
      include operative time, estimated blood loss (EBL), length of hospital stay (LOS)
      and success rates. All operations were completed laparoscopically, and there were
      no conversions to open surgery in either group. Mean operative time was 60 min
      longer in the secondary pyeloplasty group compared with primary cases, but the
      EBL, LOS and success rates were similar. A patent UPJ was confirmed in both
      groups by renal scan and/or excretory urography (intravenous pyelogram)
      examinations. RALP is a viable option in select patients with recurrent UPJO
      after previous endoscopic or open surgical repair. As expected, operative times
      were longer in these patients due to a more challenging dissection (p < 0.05).
      However, the magnification afforded by the robot allows for a precise dissection,
      and subsequently, there was no significant increase in blood loss, hospital stay
      or perioperative morbidity in our series (p > 0.05).

PMID- 16409422
TI  - Robotic assisted retroperitoneoscopic nephroureterectomy -- first experience and
      the hybrid port technique.
AB  - Robot-assisted renal surgery is usually performed transperitoneally due to more
      available space for excursion of the robotic arms. To our knowledge, we report
      the first experience with robotic retroperitoneoscopic nephroureterectomy using
      the Da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) and a
      hybrid port technique. Robotic retroperitoneal nephroureterectomy was performed
      on two male patients. One 37-year-old patient had a painful non-functioning
      hydronephrotic left kidney and megaureter; the other aged 76 had a muscle
      invasive lower left ureteric tumour. Both the procedures were successfully
      completed with the robot without conversion. Mean operative time was 182.5 min
      and estimated blood loss 75 ml. Histological examination confirmed the
      preoperative diagnoses; margins were clear in the patient with tumour.
      Postoperative recovery was uneventful. We report the technical feasibility of
      robotic retroperitoneoscopic nephroureterectomy. However, as with all new
      technology, the benefits need to be further evaluated and proven before this
      technique can be widely accepted.

PMID- 16409423
TI  - Long-term management of patients with symptoms of gastro-oesophageal reflux
      disease -- a Norwegian randomised prospective study comparing the effects of
      esomeprazole and ranitidine treatment strategies on health-related quality of
      life in a general practitioners setting.
AB  - This article reports quality of life (QoL) aspects of a study that investigated
      the efficacy of three treatment regimens in gastro-oesophageal reflux disease
      patients. Following a 4-week symptom-control phase (esomeprazole 40 mg once
      daily), patients were randomised to 6 months' esomeprazole 20 mg once daily
      continuously (n = 658), on-demand (n = 634) or ranitidine 150 mg twice daily
      continuously (n = 610). Esomeprazole 40 mg once daily improved QoL during the
      symptom-control phase. At 6 months, both esomeprazole regimens were more
      effective than ranitidine in all dimensions of the Quality of Life in Reflux and
      Dyspepsia questionnaire (p < 0.0001). Esomeprazole continuous and on-demand led
      to a significant improvement in symptoms (Overall Treatment Evaluation
      questionnaire) compared with ranitidine (continuous: 80.2%, on-demand: 77.8%, vs.
      ranitidine 47.0%; p < 0.001). Esomeprazole once daily continuously maintained QoL
      better than esomeprazole on-demand and was associated with greater patient
      satisfaction. In conclusion, esomeprazole 20 mg once daily continuously and on
      demand were more effective than ranitidine continuously for maintaining QoL.

PMID- 16409424
TI  - The effect of thyroxine-suppressive therapy in patients with solitary non-toxic
      thyroid nodules -- a randomised, double-blind, placebo-controlled study.
AB  - The efficacy of thyroxine (T(4)) for solitary non-toxic thyroid nodule remains
      uncertain. In this study, 60 patients with solitary non-toxic thyroid nodule were
      divided randomly into two groups. Group I (n = 30) received thyroxine 100
      microg/day for 6 months and group II (n = 30) received placebo. The volume of the
      thyroid nodules in 11 patients decreased more than 50% after thyroxine therapy
      (36.7%, responders). In these 11 patients, the mean serum thyroglobulin level
      decreased significantly (340 +/- 115 to 162 +/- 86 microg/l, p < 0.01). Compared
      with the non-responders (n = 19, 63.3%), the serum thyroglobulin level before
      treatment was significantly higher (340 +/- 115 vs. 220 +/- 102 microg/l, p <
      0.05). Thyroxine-suppressive therapy is proved as a useful tool in reducing
      nodule size in some patients with solitary thyroid nodules. The patients with a
      higher serum thyroglobulin level generally respond better to thyroxine
      suppressive therapy.

PMID- 16409425
TI  - Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy
      in patients with transitional cell carcinoma (AUO Trial AB 20/99).
AB  - The objectives are to evaluate and compare the response and toxicity of a 3
      weekly and a 2-weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second
      line treatment in patients with transitional cell carcinoma (TCC). Between June
      2000 and July 2001, 30 patients with progressive disease (PD) during first-line
      chemotherapy (n = 11) or relapse after adjuvant cisplatin-based chemotherapy of a
      metastatic or locally advanced TCC (n = 18) have been randomised to receive
      either six cycles (schedule A) of 3-weekly Gem (1000 mg/qm, days 1 and 8) and Pac
      (175 mg/qm, day 1) or 2-weekly treatment until disease progression (schedule B)
      with Gem (1250 mg/qm, day 1) and Pac (120 mg/qm, day 2). Restaging was performed
      after every 6 weeks by clinical imaging. Of 30 patients, one patient in schedule
      A and two patients in schedule B were not evaluable for response due to serious
      adverse events (SAEs) during the first cycle. The overall objective response (OR)
      was 44% (12 of 27) with eight complete remissions (CRs) and four partial
      remissions. Median time to progression (TTP) was 11 (3-41) months in schedule A
      and 6 (1-15+) months in schedule B. Median survival was 13 (5-46) months in
      schedule A and 9 (0-16) months in schedule B. Schedule A showed a significantly
      higher rate of CRs (7 vs. 1, p < 0.05). With a median number of six (1-6) cycles
      (A) and nine (1-23) cycles (B), TTP and survival were not significantly
      different. In schedule B, one patient had WHO grade IV anaemia and leucopenia.
      WHO grade III toxicities were seen in schedule A/B as follows: anaemia 3 (23%)/2
      (16%) patients, leucopenia 5 (38%)/2 (16%), thrombocytopenia 0/2 (16%) and
      alopecia 10 (76%)/4 (32%). The combination of Gem and Pac is an effective second
      line regimen in patients with mainly poor prognosis due to PD after cisplatin
      based chemotherapy. Except for three SAEs (uncertainly therapy related), both
      regimens were tolerated well. The 3-weekly schedule with a nonsplit Pac dose
      showed a significantly higher complete response rate in our small study
      population and, thus, might be superior to the 2-weekly schedule.

PMID- 16409426
TI  - Association between unplanned readmission rate and volume of breast cancer
      operation cases.
AB  - This study was conducted to investigate the relationship between unplanned
      readmission and breast cancer operation cases, with the assumption that the rate
      of unplanned readmission within 30 days of surgery was solely due to postsurgical
      complications. We divided hospitals into three categories based on breast cancer
      operation cases: low-volume hospitals (< or =50 annual procedures), medium-volume
      hospitals (51-99 annual procedures) and high-volume hospitals (> or =100 annual
      procedures). The medical records of 1351 subjects in 24 hospitals were
      investigated. We found unplanned readmission rates were significantly higher in
      hospitals with a lower surgical volume. From these three groups, a sample
      consisting of 1351 patients was created and 17 unplanned readmission cases (1.2%)
      were reported. Of these 17 cases, 12 (70.59%) cases were from low-volume
      hospitals. The present results indicate that unplanned readmission within 30 days
      following discharge is an important adverse outcome in breast cancer surgery.

PMID- 16409427
TI  - Antithrombotic therapy for congestive heart failure.
AB  - Patients with congestive heart failure (CHF) are at increased risk of
      thromboembolic events. However, there is much debate and uncertainty over the use
      of antithrombotic therapy in these patients. The evidence for oral
      anticoagulation is limited, although large randomised trial data are forthcoming.
      Aspirin may be detrimental for heart failure due to a possible interaction with
      angiotensin-converting enzyme inhibitors, leading to increased hospitalisations
      from decompensated heart failure. The objective of this review article is to
      summarise the available evidence regarding the risk of stroke and thromboembolic
      events in CHF patients, as well as the effectiveness and risks of antithrombotic
      therapy in these patients.

PMID- 16409428
TI  - Diabetes mellitus and stroke.
AB  - The aim of this article was to describe (i) the epidemiology and outcomes of
      stroke relating to diabetes; (ii) the pathophysiology of diabetes as a risk
      factor for stroke; (iii) the management of acute stroke in patients with
      diabetes; (iv) the evidence of primary and secondary prevention of stroke in
      patients with diabetes; and (v) the risk of new-onset diabetes using older
      antihypertensive agents. The combination of diabetes and stroke disease is a
      major cause of morbidity and mortality worldwide. Evidence from large clinical
      trials performed in patients with diabetes supports the need for aggressive and
      early intervention to target patients' cardiovascular (CV) risks in order to
      prevent the onset, recurrence and progression of acute stroke. Identification of
      at-risk patients with diabetes and metabolic syndrome has also allowed the
      delivery of early and effective intervention to reduce stroke risks, while active
      treatment during the acute phase of stroke will reduce long-term neurological and
      functional deficits. While the ongoing debate on the risk benefits of different
      antihypertensive, lipid-lowering and antiplatelet agents should not detract
      clinicians from pursuing aggressive CV risk reduction, the application of
      evidence-based medicine specifically in patients with diabetes will facilitate
      the use of appropriate agents to improve clinical outcomes. The overall
      management of patients with diabetes and acute stroke or at risk of secondary
      stroke should also include multifactorial intervention that not only targets
      patient's CV risk but also includes behavioural, lifestyle and, where
      appropriate, surgical intervention.

PMID- 16409429
TI  - A symptom-based approach to making a positive diagnosis of irritable bowel
      syndrome with constipation.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder.
      Characterised by abdominal pain or discomfort, bloating and altered bowel habit,
      IBS is a chronic recurring condition, typically affecting up to 15% of the
      Western population, IBS can be subclassified into IBS with constipation (IBS-C),
      IBS with diarrhoea (IBS-D), or IBS with alternating constipation or diarrhoea
      symptoms (IBS-A). Conventional clinical diagnosis focuses on excluding all
      potential organic causes of patient symptoms. However, a positive diagnosis of
      IBS may be established using published criteria such as the Manning and/or Rome
      criteria. While these methods are useful to identify patients with IBS who are
      suitable for enrollment into clinical trials, the criteria are relatively complex
      and not readily applicable to general practice. In this review we present an
      'identify, eliminate, probe' algorithm that may be appropriate to establish a
      positive diagnosis of patients with IBS-C, as symptoms characteristic of patients
      in this IBS subgroup are least likely to be confused with symptoms reflecting
      serious organic disease.

PMID- 16409430
TI  - A review on the treatment of acne vulgaris.
AB  - The following article reviews treatment for acne vulgaris. Selection of therapy
      should be based on clinical appearance taking into account lesion type and
      severity, as well as identification of acne scarring and the psychosocial
      disability caused by the disease.

PMID- 16409431
TI  - Scipione Riva-Rocci and the men behind the mercury sphygmomanometer.
AB  - The history of the blood pressure (BP) concept and measurements is described.
      Many scientists were involved. Among them, major triumphs were achieved by
      William Harvey during the early 1600s who announced that there is a finite amount
      of blood that circulated the body in one direction only. In the mid-1700s,
      Reverend Stephen Hales reported the first invasive measurement in horses and
      smaller animals. Poiseuille introduced in the early 1800s the mercury
      hydrodynometer and the mmHg units. Karl von-Vierordt described in 1855 that with
      enough pressure, the arterial pulse could be obliterated. He also created the
      sphygmograph, a pulse recorder usable for routine non-invasive monitoring on
      humans. In 1881, von Basch created the sphygmomanometer and the first non
      invasive BP measurements. However, in 1896, Scipione Riva-Rocci developed further
      the mercury sphygmomanometer, almost as we know it today. The sphygmomanometer
      could only be used to determine the systolic BP. Observing the pulse
      disappearance via palpitation would only allow the measuring physician to observe
      the point when the artery was fully constricted. Nikolai Korotkoff was the first
      to observe the sounds made by the constriction of the artery in 1905.

PMID- 16409432
TI  - Thyroid cancer review 3: management of medullary and undifferentiated thyroid
      cancer.
AB  - This is the last of the three review articles dealing with thyroid cancer. Over
      90% of thyroid cancer is of the differentiated type associated with a very good
      10-year disease-free survival rate. In contrast, the rare forms of thyroid cancer
      which comprise medullary thyroid cancer arising from parafollicluar C cells,
      Hurthle cell carcinoma, anaplastic carcinoma, thyroid lymphoma and squamous cell
      carcinoma are typically associated with a poorer survival rate. Management is
      based upon small retrospective cohort studies.

PMID- 16409433
TI  - Methylprednisolone aceponate in eczema and other inflammatory skin disorders -- a
      clinical update.
AB  - Methylprednisolone aceponate (MPA) has been shown to provide rapid, reliable and
      highly effective treatment of eczematous disorders, with an efficacy comparable
      to that of most reference topical corticosteroids. It also has excellent local
      and systemic tolerability. MPA is effective in the treatment of facial and scalp
      eczema and sunburn and has shown promising results in the treatment of psoriasis.
      Its rapid efficacy and lack of undesirable local and/or systemic side effects
      make MPA particularly suitable for use in children and infants. The wide range of
      formulations (0.1%) of MPA, including cream, ointment, fatty ointment, milk and
      solution, enable treatment to be tailored to the individual patient. In addition,
      MPA has the advantage of once-daily application compared with twice-daily
      treatment for other topical corticosteroids, thereby improving patient safety and
      promoting patient compliance but without compromising efficacy.

PMID- 16409434
TI  - Steroid-responsive subacute polymyositis in an adult following respiratory
      syncytial virus infection.
AB  - The role of viral infections in the aetiopathogenesis of polymyositis remains
      speculative. We report a case of profound subacute polymyositis with incipient
      ventilatory failure following serologically confirmed infection by respiratory
      syncytial virus (RSV), with a dramatic and sustained response to pulse
      corticosteroid therapy. We suggest a possible autoimmune mechanism to account for
      this sequence of events.

PMID- 16409435
TI  - Two generations with familial thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare multi-system disease
      characterised by the pentad of microangiopathic haemolytic anaemia,
      thrombocytopenia, renal dysfunction, fever and neurologic changes. A hereditary
      form of recurrent familial TTP has been described, which usually presents in
      adolescence or early adulthood and can lead to recurrent or chronic relapsing
      TTP. Genetic analyses of patients with familial TTP have linked the disease to
      chromosome 9q34, and an increased incidence is seen in people with HLA-B40 group
      antigens. We describe here an 11-year-old Egyptian girl with no significant past
      medical history who presented with new onset of bruising, petechial rash, fatigue
      and fevers and was diagnosed with familial TTP. Further testing revealed that
      both the patient and her father had the HLA-B40 group antigen and also had ADAMTS
      13 von Willebrand factor-cleaving protease deficiency as well as factor-H
      deficiency.

PMID- 16409437
TI  - Solitary actinomycotic abscesses of liver: report of two cases.
AB  - Hepatic actinomycotic abscesses are rare and secondary to other intra-abdominal
      infections. History of intra-abdominal surgery is a principal contributing factor
      for the abscess formation. Patients with hepatic actinomycotic abscess may suffer
      from fever, malaise, abdominal pain and bodyweight loss. The clinical progress of
      actinomycotic abscess is more indolent than the usual course of other pyogenic
      abscess. It is sometimes diagnosed as malignancy. This report consists of two
      cases of hepatic actinomycotic abscess mimicking tumours. Laboratory data
      revealed elevated alkaline phosphatase and leucocytosis. The abdominal computed
      tomography scan showed multiloculated lesions with peripheral contrast
      enhancement appearance. Diagnosis confirmation was based on the typical
      histologic feature of sulfur granules with inflammatory process by echo-guided
      fine needle biopsy or surgical specimen. These two cases were resolved with
      extended courses of intravenous and oral penicillin treatment.

PMID- 16409436
TI  - Spontaneous rupture of non-parasitic hepatic cyst.
AB  - Intrahepatic cysts are generally classified as congenital, traumatic, infectious
      or neoplastic. Non-parasitic hepatic cysts (NPHCs) include simple cysts and adult
      polycystic liver disease in which the liver is diffusely occupied by cysts. NPHCs
      usually reach a large size before causing symptoms, unless a complication such as
      rupture, bleeding, infection, obstructive jaundice or neoplastic transformation
      occurs. We report the case of a 67-year-old man with spontaneous rupture of
      simple liver cyst. The clinical pictures and the unusual ultrasound features of
      this rare condition are discussed.

PMID- 16409438
TI  - Familial hyperzincaemia: a rare entity.

PMID- 16409439
TI  - Rivastigmine monotherapy and combination therapy with memantine in patients with
      moderately severe Alzheimer's disease who failed to benefit from previous
      cholinesterase inhibitor treatment.
AB  - We investigated the efficacy and safety of rivastigmine alone and combined with
      memantine in Alzheimer's disease patients previously failing on donepezil or
      galantamine. This was a prospective, open-label, multicentre study. After
      stopping donepezil or galantamine, patients received rivastigmine 3-12 mg/day for
      16 weeks. Non-responders to rivastigmine monotherapy at week 16 received
      memantine 5-20 mg/day plus rivastigmine for 12 weeks. The primary efficacy
      parameter was response (Mini-Mental State Examination equal or better than at
      week 16) to dual therapy at week 28. Secondary criteria were changes on cognitive
      and behavioural scales. Two hundred and two patients were included. Ninety-three
      (46.3%) patients responded to rivastigmine monotherapy. Of 86 patients receiving
      additional memantine for another 12 weeks, 67 (77.9%) responded. Combination
      therapy caused no apparent safety concerns. When patients fail on donepezil or
      galantamine, switching to rivastigmine may improve cognition and behaviour.
      Should they continue to deteriorate, the addition of memantine may be beneficial.

PMID- 16409440
TI  - Efficacy, tolerability and safety of darifenacin, an M(3) selective receptor
      antagonist: an investigation of warning time in patients with OAB.
AB  - This double-blind, randomised placebo-controlled, multicentre study evaluated the
      efficacy, tolerability and safety of 12 weeks' treatment with controlled release
      darifenacin 15 mg once daily (qd), in 445 patients with overactive bladder (OAB).
      The primary endpoint was warning time (time from first sensation of urgency to
      voiding), and secondary endpoints included urge incontinence episodes and volume
      voided. Darifenacin treatment resulted in numerical increases in warning time,
      but these were not significant compared with placebo -- highlighting difficulties
      in assessing this parameter. Significant improvements were seen with darifenacin
      vs. placebo in urge incontinence episodes/week, volume voided and quality of life
      (QoL). Darifenacin was associated with increases in urgency-free time (UFT; time
      between any void to the next urgency event) vs. placebo. Treatment was well
      tolerated; the most commonly reported adverse events were the typical
      antimuscarinic effects of dry mouth and constipation, both infrequently leading
      to discontinuation. This study demonstrated the difficulty in measuring warning
      time, due in part to its subjective nature; the authors believe further
      investigation is warranted to allow urgency to be better defined. Further
      investigation of UFT is required to determine its role in evaluating urgency. The
      study confirmed that darifenacin 15 mg qd is an effective and well-tolerated
      treatment for OAB, which improves QoL.

PMID- 16409442
TI  - Is antithrombotic prophylaxis required in cancer patients with central venous
      catheters? Yes for special patient groups.

PMID- 16409443
TI  - Is antithrombotic prophylaxis required in cancer patients with central venous
      catheters? No.

PMID- 16409444
TI  - Is antithrombotic prophylaxis required in cancer patients with central venous
      catheters? Still an open question.

PMID- 16409445
TI  - Inherited defects of coagulation factor V: the hemorrhagic side.
AB  - Coagulation factor V (FV) is the protein cofactor required in vivo for the rapid
      generation of thrombin catalyzed by the prothrombinase complex. It also
      represents a central regulator in the early phases of blood clot formation, as it
      contributes to the anticoagulant pathway by participating in the downregulation
      of factor VIII activity. Conversion of precursor FV to either a procoagulant or
      anticoagulant cofactor depends on the local concentration of procoagulant and
      anticoagulant enzymes, so that FV may be regarded as a daring tight-rope walker
      gently balancing opposite forces. Given this dual role, genetic defects in the FV
      gene may result in opposite phenotypes (hemorrhagic or thrombotic). Besides a
      concise description on the structural, procoagulant and anticoagulant properties
      of FV, this review will focus on bleeding disorders associated with altered
      levels of this molecule. Particular attention will be paid to the mutational
      spectrum of type I FV deficiency, which is characterized by a remarkable genetic
      heterogeneity and by an uneven distribution of mutations throughout the FV gene.

PMID- 16409446
TI  - The importance of measuring anticardiolipin antibodies.

PMID- 16409447
TI  - A prospective study of anticardiolipin antibodies as a risk factor for venous
      thrombosis in a general population (the HUNT study).
AB  - We prospectively examined whether there is an association between elevated
      anticardiolipin antibody levels and the risk for a future first venous thrombosis
      (VT) in a general population. We studied this in a large population-based nested
      case-cohort study of 508 VT cases and 1464 matched control subjects from a cohort
      of 66,140 participants in the Health Study of Nord-Trondelag in Norway. Venous
      thrombosis was validated using standardized criteria for venous thrombosis and
      pulmonary embolism. Prethrombotic serum anticardiolipin antibodies were measured
      by an enzyme-linked immunoassay. There was no association between elevated
      anticardiolipin antibody levels and subsequent venous thrombosis, overall or
      after stratification by sex, different age groups or idiopathic vs. secondary
      thrombosis. The overall odds ratio was 1.11 (95% CI: 0.71-1.74) for greater than
      vs. less than the 95th percentile of anticardiolipin antibody levels. In
      conclusion, in this general population sample elevated anticardiolipin antibody
      levels was not a risk factor for subsequent venous thrombosis.

PMID- 16409448
TI  - Plasma D-dimer assays in the diagnosis of venous thromboembolism in cancer
      patients.

PMID- 16409449
TI  - Combined use of clinical pretest probability and D-dimer test in cancer patients
      with clinically suspected deep venous thrombosis.
AB  - BACKGROUND: The value of the D-dimer (DD) test in combination with the clinical
      pretest probability (PTP) has not been evaluated in cancer patients with
      suspected deep vein thrombosis (DVT), whereas this group of patients usually
      accounts for 10-25% of clinically suspected DVT. METHODS: A cohort of 2066
      consecutive patients with clinically suspected DVT was investigated. Patients
      were judged to be positive or negative for DVT according to the outcomes of
      serial compression ultrasound and a 3-month follow-up period with imaging test
      verification of the symptomatic cases. Diagnostic accuracy indices of the DD test
      according to the PTP score were assessed in patients with and without cancer.
      RESULTS: Of the cohort, 244 (11%) were known to have cancer at presentation. A
      venous thromboembolic event was diagnosed in 41% of the patients with cancer and
      in 22% of the patients without malignancy. Among the cancer patients, 17% were
      considered to have a low PTP, 35% a moderate and 41% a high PTP. The negative
      predictive value (NPV) of the DD test was 100% (95% CI, 85-100) and 97% (95% CI,
      88-99) among cancer patients with low PTP or low-moderate PTP. In the absence of
      malignancy, the corresponding NPV were 98% and 97%, respectively. The specificity
      of the DD test progressively decreased moving from the low to the higher PTP.
      CONCLUSIONS: In cancer patients with clinically suspected DVT, a negative DD
      might be useful in excluding the diagnosis within the low or low-moderate PTP
      groups. More studies are warranted to confirm these findings.

PMID- 16409450
TI  - Adding the vessel wall to Virchow's triad.

PMID- 16409451
TI  - Thrombin generation in vascular tissue.
AB  - BACKGROUND: Classically, it is thought that the vast majority of thrombin is
      generated on the surface of platelets, however, thrombotic events occur in
      patients despite treatment with potent antiplatelet agents. METHODS AND RESULTS:
      In freshly harvested left internal mammary artery (IMA) sections, addition of
      CaCl2 and platelet-poor plasma (PPP) were sufficient to stimulate a profound
      burst of thrombin and this effect was inhibited by antitissue factor antibodies.
      Ultracentrifugation of PPP to remove platelet microparticles had no effect on
      thrombin generation. Both the extrinsic and factor VIII-dependent pathways were
      necessary for IMA-supported thrombin generation as PPP derived from individuals
      deficient in factors V, VII, VIII or X did not support thrombin production. Small
      amounts of thrombin were generated utilizing factor IX (FIX)-deficient plasma,
      however, thrombin was not generated by aorta from FIX-deficient mice when FIX
      deficient plasma was used. The addition of non-lipidated tissue factor (0.6 pM)
      and CaCl2 to actively proliferating cultured human aortic smooth muscle cells
      (SMC) resulted in a pronounced burst of thrombin generation occurring between 3
      and 15 min after treatment. In the absence of tissue factor, thrombin was
      generated but at a slower rate and with a peak value 26% of that observed in the
      presence of tissue factor. CONCLUSION: Significant thrombin generation can occur
      on vascular tissue in the absence of platelets or platelet microparticles and on
      the surface of non-apoptotic SMC.

PMID- 16409452
TI  - Hormone replacement therapy and risk of venous thromboembolism--still unresolved
      questions.

PMID- 16409453
TI  - New epidemiological risk factors for venous thromboembolism (VTE) after
      menopause.

PMID- 16409454
TI  - Indicators of lifetime endogenous estrogen exposure and risk of venous
      thromboembolism.
AB  - BACKGROUND: Lifetime estrogen exposure has been related to breast cancer risk,
      osteoporosis, and cardiovascular disease but data on venous thromboembolism (VTE)
      risk are limited. METHODS: Data from a hospital-based case-control study among
      608 postmenopausal women (191 with a first episode of idiopathic VTE and 417 age
      matched controls) were used to determine whether estrogen exposure, as assessed
      by age at menopause [classified as early (< or = 45 years), normal (46-54 years)
      and late menopause (> or = 55 years)] and parity, was associated with the risk of
      VTE. RESULTS: After adjustment for potential confounding variables, the risk of
      VTE was increased with each year's delay in the menopause [odds ratio (OR) =
      1.06, 95% confidence interval (CI) = 1.02-1.10, P < 0.0075]. When compared with
      women with normal menopause used as a reference, the adjusted OR for VTE was 0.59
      (95% CI = 0.36-0.97) and 2.53 (95% CI = 1.28-4.99) for women with early menopause
      and late menopause, respectively (P = 0.001). Adjusted OR for VTE was also higher
      for women with more than two children when compared with those with less than or
      equal to two children (1.56, 95% CI = 1.03-2.34, P = 0.03). The lowest risk of
      VTE was observed in women with early menopause and lower parity (adjusted OR =
      0.60, 95% CI = 0.30-1.24), the highest risk was among women with late menopause
      who have had more than two children (adjusted OR = 3.41, 95% CI = 1.46-9.25).
      CONCLUSION: These results show that the longer exposure to endogenous estrogen is
      associated with an increased VTE risk.

PMID- 16409455
TI  - Treatment with combined oral contraceptives induces a rise in serum C-reactive
      protein in the absence of a general inflammatory response.
AB  - BACKGROUND: The role of inflammation in the pathogenesis of cardiovascular
      disease is well established. C-reactive protein (CRP) is the strongest
      independent predictor of myocardial infarction and stroke in women. Recent
      studies have indicated that CRP levels are raised during use of combined oral
      contraceptives (COCs). OBJECTIVES: The aim of the study was to investigate the
      effect of COCs on serum CRP levels and to indicate the underlying mechanisms of
      an expected increase. METHOD: In a prospective randomized cross over-study 35
      women used two different preparations of COC, one second and one third
      generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6),
      tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin
      and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor
      binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two
      treatments. E-selectin, von Willebrand factor and factor VIII concentrations in
      plasma were also measured. RESULTS: A rise in serum CRP was observed during both
      treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg
      L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The
      serum levels of SAA increased slightly during treatment with the third generation
      COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered
      IGF-I and raised IGFBP-1 and IGFBP-3 concentrations. CONCLUSION: The raised serum
      CRP concentration during treatment with COCs appears to be related to a direct
      effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated
      inflammation, endothelial activation or induction of insulin resistance.

PMID- 16409456
TI  - Fixed dosage of low-molecular-weight heparins causes large individual variation
      in coagulability, only partly correlated to body weight.
AB  - BACKGROUND: Low-molecular-weight heparins (LMWHs) are routinely given without the
      control of their effect on coagulation. The endogenous thrombin potential (ETP)
      is a sensitive detector of the heparin effect. QUESTION: What is the
      interindividual variation in TG after a fixed dose of LMWH in normal volunteers,
      is it explained by variation in weight? METHODS: Subcutaneous (s.c.) injection,
      in 12 healthy volunteers, of 9000 aXa-units of unfractionated heparin (UFH) and
      of three heparins with narrow MW distribution around 10.5, 6.0 and 4.5 kD.
      Measurement of anti-thrombin (aIIa) and antifactor Xa (aXa)-activities and ETP at
      11 time points over 24 h. RESULTS: The coefficient of variation (CV) of the AUCs
      of aXa- and aIIa-activities is 50% for UFH and 22-37% for LMWHs. Because of the
      hyperbolic form of the dose-response curve, the CV of the inhibition of the ETP
      is lower: 32% for UFH and 13-21% for the LMWHs. Fixed dosage of LMWH caused under
      dosage in 10-13% of the samples and over-dosage in 5-11%. High or low response is
      an individual property independent of the type of heparin injected and only
      partially explained by variation in body weight. CONCLUSION: Optimized individual
      dosage of LMWH is possible through recognition of high and low responders, which
      requires one measurement of the heparin concentration or, preferably, the heparin
      effect on the ETP, 2-5 h after a first injection.

PMID- 16409457
TI  - Treatment effects of high-dose antithrombin without concomitant heparin in
      patients with severe sepsis with or without disseminated intravascular
      coagulation.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious
      complication of sepsis that is associated with a high mortality. OBJECTIVES:
      Using the adapted International Society on Thrombosis and Haemostasis (ISTH)
      diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high
      dose antithrombin (AT) in patients with severe sepsis with or without DIC.
      PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis
      (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not
      receive concomitant heparin and had sufficient data for DIC determination.
      RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo
      treated patients was associated with an excess risk of mortality (28-day
      mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an
      absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02)
      whereas in patients without DIC no effect on 28-day mortality was seen (0.1%
      reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients
      with and without DIC were higher compared with placebo (major bleeding rates:
      7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without
      DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic
      patients with DIC may result in a significant mortality reduction. The adapted
      ISTH DIC score may identify patients with severe sepsis who potentially benefit
      from high-dose AT treatment.

PMID- 16409458
TI  - C-reactive protein contributes to the hypercoagulable state in coronary artery
      disease.
AB  - OBJECTIVES: Elevated plasma C-reactive protein (CRP) levels predict coronary
      events, but it is unclear whether CRP plays a role in thrombosis associated with
      these events. We investigated tissue factor (TF) induction by CRP on peripheral
      blood mononuclear cells (PBMC) from patients with coronary disease. PATIENTS AND
      METHODS: PBMC from 35 patients with stable angina (SA) in study 1, 10 male
      patients with SA, 10 with unstable angina (UA) and 10 matched controls in study
      2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in
      study 3 were stimulated with CRP, interferon-gamma (IFN) or lipopolysaccharide
      (LPS), or their combination. PBMC from additional normal donors were also
      stimulated with CRP in adherent and non-adherent conditions, and TF activity,
      antigen and mRNA expression detected. RESULTS: CRP (5-25 microg mL(-1)) dose
      dependently induced more TF on PBMC from SA patients than 42 contemporary
      controls (P = 0.001, study 1). Compared with controls, patients with SA or UA had
      higher basal, and much higher CRP- or CRP/LPS-induced monocyte TF activity
      although serum CRP levels were similar (study 2). IFN induced monocyte TF
      activity in patients with angina, but not in controls. Basal or CRP-induced TF
      levels did not differ between controls and ID, even though ID patients had much
      higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated
      with serum CRP levels in controls (P = 0.005) and ID (P = 0.007) in study 3, but
      not in patients with angina (P =0.84) in study 2. CRP induced more TF activity,
      protein and mRNA under adherent than non-adherent conditions implying that it may
      mainly target macrophages in lymphocyte-rich lesions. CONCLUSIONS: Our results
      indicate that monocytes from patients with angina are preactivated and express TF
      but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further
      increase TF levels that may contribute to the hypercoagulable state in coronary
      disease.

PMID- 16409459
TI  - Soluble intracellular adhesion molecule-1 is associated with cardiovascular
      disease risk and mortality in older adults.
AB  - BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte
      endothelial attachment, a process crucial to atherosclerosis. Circulating soluble
      ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD)
      progression. OBJECTIVES: We examined the association of sICAM-1 with measures of
      subclinical CVD and risk of incident CVD events and death in older men and women
      (age > or = 65 years) from the Cardiovascular Health Study. METHODS: Selected
      participants were free of clinical CVD at baseline. Non-exclusive incident case
      groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327),
      and death (n = 842; CVD death = 310). A total 643 subjects were free of events
      during follow-up. RESULTS: sICAM-1 was positively associated with C-reactive
      protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these
      older men and women. In Cox regression models adjusted for age, gender, and race,
      increasing levels of sICAM-1 were associated with increased risk of all cause
      mortality in men and women. Hazard ratios (95% confidence intervals) for a one
      standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men
      and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD
      death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no
      associations of sICAM-1 with non-fatal CVD events. CONCLUSIONS: While sICAM-1 was
      associated with death in older men and women, there was a more marked association
      between sICAM-1 and CVD death in women.

PMID- 16409460
TI  - Co-localization of von Willebrand factor with platelet thrombi, tissue factor and
      platelets with fibrin, and consistent presence of inflammatory cells in coronary
      thrombi obtained by an aspiration device from patients with acute myocardial
      infarction.
AB  - BACKGROUND: Detailed histochemical analysis of coronary thrombi obtained freshly
      from acute phase of myocardial infarction patients may provide information
      necessary to understand the mechanism of coronary occlusive thrombus formation.
      METHODS AND RESULTS: Coronary thrombi causing myocardial infarction were obtained
      from 10 consecutive patients of myocardial infarction in the acute phase, using a
      newly developed aspiration catheter. All the fixed specimens of coronary thrombi,
      by hematoxylin and eosin staining, were found to contain three major
      constituents, namely, platelets, densely packed fibrin and inflammatory cells,
      including polymorphonuclear and mononuclear cells, although their distribution in
      each specimen is totally heterogeneous. Immunohistochemical staining revealed the
      prominent presence of von Willebrand factor (VWF) at the sites of platelet
      accumulation, presence of tissue factor and platelets at the sites of deposition
      of fibrin fibrils. It also revealed the presence of CD16-, CD45- and CD34
      positive cells, yet the functional roles of these cells have still to be
      elucidated. There are weak positive correlation between the number of
      inflammatory cells involved in the unit area of coronary thrombi specimen and the
      time of collection of the specimens after the onset of chest pain. CONCLUSIONS:
      In spite of various limitations, our results contain information suggesting the
      possible role of VWF in platelet-thrombus formation, possible important role
      played by tissue factor and activated platelets in the formation of fibrin
      fibrils, and the positive relationship between inflammatory cells migration and
      the formation of occlusive thrombi in human coronary arteries.

PMID- 16409461
TI  - Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous
      thromboembolism after total hip replacement.
AB  - BACKGROUND: Joint replacement surgery is an appropriate model for dose-ranging
      studies investigating new anticoagulants. OBJECTIVES: To assess the efficacy and
      safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative
      to enoxaparin in patients undergoing elective total hip replacement. METHODS: In
      this double-blind, double-dummy, dose-ranging study, patients were randomized to
      oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery,
      or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery.
      Treatment was continued until mandatory bilateral venography was performed 5-9
      days after surgery. RESULTS: Of 706 patients treated, 548 were eligible for the
      primary efficacy analysis. The primary efficacy endpoint was the incidence of any
      deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality;
      rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg
      b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy
      analysis did not demonstrate any significant trend in dose-response relationship
      for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding;
      there was a significant increase in the frequency of events with increasing doses
      of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY
      59-7939 doses and enoxaparin. CONCLUSIONS: When efficacy and safety were
      considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg
      b.i.d., compared favorably with enoxaparin for the prevention of venous
      thromboembolism in patients undergoing elective total hip replacement.

PMID- 16409462
TI  - A rapid enzyme-linked assay for ADAMTS-13.
AB  - BACKGROUND: A deficiency in the plasma metalloprotease ADAMTS-13 is associated
      with deposition of microvascular thrombi that cause thrombotic thrombocytopenic
      purpura. Current assays for ADAMTS-13 are technically complex and time-consuming.
      The objective of this study is to devise a rapid and sensitive assay for ADAMTS
      13 activity in plasma and verify the site of cleavage. METHOD: A new enzyme
      linked substrate, which contains a core ADAMTS-13-specific peptide conjugated to
      horseradish peroxidase (HRP) at the N-terminus, and labeled with biotin at the C
      terminus, was constructed. After cleavage of this substrate by plasma ADAMTS-13
      and removal of uncleaved substrate by adsorption with streptavidin-agarose,
      ADAMTS-13 activity was quantitated by determining the unadsorbed HRP activity
      remaining in solution. Levels of inhibitory antibodies in test plasma were also
      determined by measuring the residual ADAMTS-13 activity after varying amounts of
      test plasma were incubated with a known amount of ADAMTS-13. RESULTS: Plasma
      ADAMTS-13 activity was readily determined in approximately 60 min (coefficient of
      variation 5.8%) using 1 microL of test plasma. Amino acid sequencing of the
      cleavage product confirmed that cleavage occurred at the Tyr1605-Met1606 bond in
      the substrate. ADAMTS-13 activities in the plasma of five TTP patients were below
      2%. Inhibitory antibody titers in these samples varied from undetectable to 81 BU
      mL(-1). CONCLUSION: The HRP-linked substrate provides a rapid, sensitive, and
      reproducible way of determining the levels of ADAMTS-13 activity and inhibitory
      antibodies in plasma.

PMID- 16409463
TI  - An association of candidate gene haplotypes and bleeding severity in von
      Willebrand disease type 2A, 2B, and 2M pedigrees.
AB  - We analyzed the association of bleeding severity with candidate gene haplotypes
      within pedigrees of 11 index cases of von Willebrand disease (VWD) type 2 (two
      type 2A, three type 2B and six type 2M), using the QTL Association model (MENDEL
      5.5). In addition to the 11 index cases, these pedigrees included 47 affected and
      49 unaffected relatives, as defined by VWF mutations and/or phenotype. A bleeding
      severity score was derived from a detailed history and adjusted for age. Donors
      were genotyped using a primer extension method, and eight candidate genes were
      selected for analysis. VWF antigen (or ristocetin cofactor activity) levels had
      the strongest influence on bleeding severity score. After Bonferroni correction
      for multiple testing, only ITGA2 promoter haplotype -52T was associated with an
      increased bleeding severity score (P < 0.01). This association remained
      statistically significant when the three type 2B pedigrees were excluded (P =
      0.012) or when gender-specific bleeding categories were excluded (P < 0.01). The
      major haplotypes of seven other candidate genes, GP1BA, ITGA2B, ITGB3, GP6, VWF,
      FGB, and IL6, were not associated with bleeding severity. These results establish
      that genetic differences in the expression of the integrin subunit alpha2 can
      influence the bleeding phenotype of VWD type 2 and complement our previous
      findings in VWD type 1. Genetically controlled attenuation of platelet collagen
      receptor expression can influence risk for morbidity in clinical settings where
      hemostasis is compromised.

PMID- 16409464
TI  - Mutations C1157F and C1234W of von Willebrand factor cause intracellular
      retention with defective multimerization and secretion.
AB  - The D3 domain of von Willebrand factor (VWF) is involved in the multimerization
      process of the protein through the formation of disulfide bridges. We identified
      heterozygous substitutions, C1157F and C1234W, in the VWF D3 domain in two
      unrelated families with unclassified and type 2A von Willebrand disease,
      respectively. VWF was characterized by a low plasmatic level, an abnormal binding
      to platelet GPIb and a high capacity of secretion from endothelial cells
      following DDAVP infusion. Using site-directed mutagenesis and expression in
      mammalian cells, we have investigated the impact of these mutations upon the
      multimerization, secretion and storage of VWF. Using COS-7 cells both mutated
      recombinant VWF (rVWF) displayed only lower molecular weight multimers. Pulse
      chase analysis and endoglycosidase H digestion experiments showed the
      intracellular retention of mutated rVWF in pre-Golgi compartments. Study of
      hybrid rVWF obtained with a constant amount of wild-type (WT) DNA and increasing
      proportions of mutated plasmids established that both substitutions reduced the
      release of WT VWF in a dose-dependent manner and failed to form high molecular
      weight multimers. Using transfected AtT-20 stable cell lines, we observed similar
      granular storage of the two mutants and WT rVWF. Our data suggest that cysteines
      1157 and 1234 play a crucial role in the early step of the folding of the
      molecule required for a normal transport pathway, maturation and constitutive
      secretion. In contrast, their substitution does not prevent the storage and
      inducible secretion of VWF.

PMID- 16409466
TI  - The cleaved and latent forms of antithrombin are normal constituents of blood
      plasma: a quantitative method to measure cleaved antithrombin.
AB  - Antithrombin (AT), a member of the serine protease inhibitor family, is the key
      regulator of thrombin activity in vivo. Thrombin inhibition is accomplished by
      the formation of covalent thrombin-AT (TAT) complex. The rate of inhibition is
      accelerated by heparin, which also leads to the formation of a substantial amount
      of cleaved AT. We produced a murine monoclonal antibody (mAb) (M9) that is
      specific for the two forms of AT, in which the reactive center loop is inserted
      into beta-sheet A, i.e. cleaved and latent AT. The antibody has no measurable
      affinity for native AT. Using M9 as a catcher antibody in conjunction with a mAb
      (M27) that does not bind latent AT, we developed a sandwich assay that measures
      cleaved AT without interference from latent and native AT. The concentration in
      healthy subjects was determined to be 1.3 mg L(-1) (range: 1.0-1.9), which was
      about 100-fold lower than the plasma concentration of native AT and 1000-fold
      higher than the concentration of the TAT complex. The cleaved AT concentration is
      higher than what would be expected from the rate of formation of cleaved AT in
      vitro in conjunction with TAT complex formation in the presence of heparin. The
      concentration of cleaved AT did not correlate with the TAT concentration in
      plasma from patients with venous thrombosis.

PMID- 16409465
TI  - Identification and characterization of murine alternatively spliced tissue
      factor.
AB  - Tissue factor (TF) is a transmembrane glycoprotein that initiates coagulation and
      plays a critical role in regulating hemostasis and thrombosis. We have recently
      reported a naturally occurring, soluble form of human tissue factor (asTF)
      generated by alternative splicing. This splice variant has a novel C-terminus
      with no homology to that of the full-length TF (flTF), lacks a transmembrane
      domain, and is active in the presence of phospholipids. Mouse models offer unique
      opportunities to examine the relative importance of flTF and asTF in mediating
      thrombosis, the response to arterial injury, and ischemic damage. To that end, we
      have identified and characterized murine asTF (masTF). Like the human splice
      variant, masTF lacks a transmembrane domain and has a unique C-terminus. We have
      generated antibodies specific to masTF and murine flTF (mflTF) to examine the
      expression of both forms of TF. masTF antigen is widely and abundantly expressed,
      with a pattern similar to that of mflTF, in adult tissues, in experimentally
      induced thrombi, and during development. These studies demonstrate that masTF
      contributes to the pool of total TF and may thus play an important role in
      mediating TF-dependent processes.

PMID- 16409467
TI  - Fatal thrombosis of antithrombin-deficient mice is rescued differently in the
      heart and liver by intercrossing with low tissue factor mice.
AB  - BACKGROUND: We previously reported that the targeted disruption of murine
      antithrombin (AT) gene resulted in embryonic lethality before 16.5 gestational
      days (gd) because of severe cardiac and hepatic thrombosis. OBJECTIVE AND
      METHODS: To investigate the influences of lowered tissue factor (TF) activity
      upon hypercoagulation of AT-/- embryos, we crossed AT+/- with low TF (mTF-/-
      hTF+) mice to yield homozygous AT-deficient mice with the extremely low TF
      activity, that is expressed from the inserted human TF mini gene. RESULTS: AT-/-
      embryos either with 50% TF (AT-/- mTF+/- hTF+) or with low (approximately 1% TF,
      AT-/- mTF-/- hTF+) were not born, although the survival was prolonged until 18.5
      gd. In both genotypes, histological examination showed disseminated thrombosis in
      hepatic sinusoidal space or in the portal veins, suggesting that the
      thrombogenesis caused loss of hepatic blood flow. As in original AT-/-, AT-/-
      mTF+/- hTF+ showed subcutaneous (s.c.) bleeding and also suffered from the
      myocardial degeneration apparently because of coronary thrombus formation.
      However, AT-/- mTF-/- hTF+ had no skin hemorrhage and the thrombosis and
      degeneration were completely abolished in the heart. Myocardium of adult low TF
      mice had exhibited fibrosis secondary to hemorrhage; however, it was
      significantly decreased in low TF mice with AT+/-. CONCLUSIONS: Our current model
      suggests that, in the heart, TF plays an important role in the thrombogenesis and
      it counterbalances AT-dependent anticoagulation. AT may be a potent anticoagulant
      during mice development and the activation and subsequent regulation of TF
      procoagulant activity take place differently between the liver and the heart.
      These differences appear to point to local regulatory mechanisms in murine
      hemostasis.

PMID- 16409468
TI  - Molecular bases of type II protein S deficiency: the I203-D204 deletion in the
      EGF4 domain alters GLA domain function.
AB  - OBJECTIVE: To characterize the first type II protein S (PS) deficiency affecting
      the epidermal growth factor (EGF)4 domain, a calcium-binding module with a poorly
      defined functional role. PATIENTS: The proband suffered from recurrent deep vein
      thrombosis and showed reduced PS anticoagulant activity (31%), and total, free PS
      antigen and C4bBP levels in the normal range. RESULTS: Reverse transcription
      polymerase chain reaction analysis showed the presence of the IVSg-2A/T splicing
      mutation that, by activating a cryptic splice site, causes the deletion of codons
      Ile203 and Asp204. Free PS, immunopurified from proband's plasma, showed an
      altered electrophoretic pattern in native condition or in the presence of Ca2+.
      The recombinant PS (rPS) mutant showed reduced anticoagulant (<10%) and activated
      protein C-independent activities (24-38%) when compared with wild-type rPS
      (rPSwt). Binding of the rPS variant to phospholipid vesicles (Kd 235.7 +/- 30.8
      nM, rPSwt; Kd 15.2 +/- 0.9 nM) as well as to Ca2+-dependent conformation-specific
      monoclonal antibodies for GLA domain was significantly reduced. CONCLUSIONS:
      These data aid in the characterization of the functional role of the EGF4 domain
      in the anticoagulant activities of PS and in defining the thrombophilic nature of
      type II PS deficiency.

PMID- 16409469
TI  - Prerequisites for recombinant factor VIIa-induced thrombin generation in plasmas
      deficient in factors VIII, IX or XI.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa) used for the treatment of hemophilia
      A or B patients with an inhibitor is hemostatically effective because it induces
      thrombin generation (TG), despite grossly impaired FVIII- and FIX-dependent
      amplification of FX activation. Tissue factor (TF) and or activated platelets
      were shown to be essential for the rFVIIa activity. OBJECTIVE: To evaluate the
      relative effects of TF and phospholipids on rFVIIa-induced TG in FVIII-, FIX- and
      FXI-deficient plasmas. METHODS: Phospholipids had an independent effect that was
      augmented by TF. The contribution of blood-borne TF in FVIII-, FIX- and FXI
      deficient plasma to rFVIIa-induced TG was demonstrated by removing microparticles
      and use of anti-TF antibodies. RESULTS: At increasing concentrations of rFVIIa,
      the dependence of rFVIIa-induced TG on TF declined, but the presence of
      phospholipids was essential. rFVIIa was also shown to activate purified FIX and
      FX in the presence of phospholipids and absence of TF. rFVIIa-induced TG was
      dramatically augmented in FVIII- or FIX-deficient plasma in which the level of
      FVIII or FIX was increased to 1 or 2 U dL(-1). CONCLUSIONS: The data indicate
      that rFVIIa-induced TG is affected by TF, phospholipids, rFVIIa concentration,
      and the presence of FVIII and FIX.

PMID- 16409470
TI  - Evaluation of low PAI-1 activity as a risk factor for hemorrhagic diathesis.
AB  - BACKGROUND: Prospective studies of the epidemiology and clinical significance of
      low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking.
      OBJECTIVE: To evaluate the prevalence of low PAI-1 activity in patients with a
      bleeding tendency in comparison with a normal population. METHODS: In 586
      consecutive patients, referred because of bleeding symptoms, we added analyses of
      PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA-PAI-1)
      to the routine investigation, consisting of platelet count, bleeding time,
      prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII,
      von Willebrand factor activity, and antigen. Controls were 100 blood donors and
      100 age- and sex-matched healthy individuals. The latter were also evaluated
      regarding the previous bleeding episodes. The bleeding history was classified as
      clinically significant or not, and the criteria were fulfilled in 75% of the
      patients and 18% of the healthy controls. RESULTS: The routine laboratory
      investigation of the patients was negative in 57%. Low PAI-1 activity, defined as
      <1.0 U mL(-1), was found in 23% of the patients and in 13% and 10% of the blood
      donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11-3.77
      and 2.75; 1.39-5.42, respectively). The difference remained statistically
      significant after the adjustment for body mass index, use of estrogens, sex and
      age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22-8.56, P =
      0.019). The distribution of the 4G/5G genotypes in the patients was not different
      from that of two control populations. No specific symptom predicted for low PAI
      1, which did not aggravate the clinical picture in association with the other
      hemostatic defects. Low tPA-PAI-1 was not associated with the increased bleeding
      tendency. CONCLUSION: Low PAI-1 activity is common in patients with a bleeding
      diathesis, but it is a risk factor of minor clinical importance and not
      associated with specific bleeding manifestations.

PMID- 16409471
TI  - Activation of p38 MAPKinase/cPLA2 pathway in homocysteine-treated platelets.
AB  - Hyperhomocysteinemia is considered a risk factor in arterial and venous
      thrombosis. The mechanism by which homocysteine (HCy) supports atherothrombosis
      is still unknown and may be multifactorial. Earlier in vitro studies demonstrated
      that HCy induced arachidonic acid release and increased thromboxane B2 (TXB2)
      formation. In this work, we found that HCy stimulated the rapid and sustained
      phosphorylation of platelet p38 mitogen-activated protein kinase (p38 MAPK). The
      effect was time- and dose-dependent. The HCy effect on p38 MAPK phosphorylation
      was prevented by N-acetyl-L-cysteine and iloprost and was partially inhibited by
      nordihydroguaiaretic acid. Moreover, the incubation of platelets with HCy led to
      the phosphorylation of cytosolic phospholipase A2 (cPLA2). In addition HCy
      promoted cPLA2 activation, assessed as arachidonic acid release. The cPLA2
      phosphorylation and activation were both impaired by the inhibition of p38 MAPK
      through SB203580. This effect was not complete, reaching at the most the 50% of
      the total. In FURA 2-loaded platelets, HCy induced a dose-dependent intracellular
      calcium rise suggesting that the calcium elevation promoted by HCy could
      participate in the cPLA2 activation, leading to arachidonic acid release and TXB2
      formation. In conclusion, our data provide insight into the mechanisms of
      platelet activation induced by HCy, suggesting that the p38 MAPK/cPLA2 pathway
      could play a relevant role in platelet hyperactivity described in
      hyperhomocysteinemia.

PMID- 16409472
TI  - Synthesis of GPIb beta with novel transmembrane and cytoplasmic sequences in a
      Bernard-Soulier patient resulting in GPIb-defective signaling in CHO cells.
AB  - The molecular defect of a new Bernard-Soulier patient, originating from Morocco
      and presenting thrombocytopenia with large platelets and an absence of ristocetin
      induced platelet agglutination, has been identified and reproduced in transfected
      heterologous cells. Gene sequencing revealed insertion of a guanine in the domain
      coding for the transmembrane region of the glycoprotein (GP) Ib beta subunit.
      This mutation causes a translational frame shift, which creates putative novel
      transmembrane and cytoplasmic 37 and 125 amino acids domains, respectively. A 34
      kDa immunoreactive GPIb beta band, instead of the normal 26 kDa subunit, was
      detected by Western blotting in lysates from the patient's platelets and from
      transfected cells and in immunoprecipitates of metabolically labeled cells. The
      abnormal subunit did not associate with GPIb alpha and was mainly intracellular,
      although a significant fraction could reach the cell surface. Cells expressing
      the mutant GPIb-IX complex adhered to a von Willebrand factor matrix but were
      unable to change shape, unlike cells expressing the wild-type receptor. These
      results strongly suggest a novel role of the GPIb beta subunit and its
      transmembrane-intracellular region in GPIb-VWF-dependent signaling, in addition
      to a role in correct assembly and cell surface targeting of the GPIb-V-IX
      complex.

PMID- 16409474
TI  - CHO cells expressing the high affinity alpha(IIb)beta3 T562N integrin demonstrate
      enhanced adhesion under shear.
AB  - BACKGROUND: Alpha(IIb)beta3-mediated platelet adhesive interactions in the
      vasculature, which are dependent on the functional state of this receptor, may be
      sensitive to shear forces. OBJECTIVES: To evaluate the influence of the
      alpha(IIb)beta3 affinity state on cell attachment under flow, we compared Chinese
      hamster ovary cells expressing the low affinity alpha(IIb)beta3 wild-type (wt)
      receptor to those expressing the high affinity alpha(IIb)beta3 T562N receptor.
      MATERIALS AND METHODS: We designed a real-time videomicroscopy adhesion assay for
      von Willebrand factor (VWF) or fibrinogen under flow conditions. RESULTS: At 50
      s(-1), alpha(IIb)beta3 T562N supported higher cell adhesion to fibrinogen (63.3
      +/- 2.9 cells/field) than alpha(IIb)beta3 wt (38.7 +/- 2.4 cells/field, P <
      0.0001). At 100 s(-1), alpha(IIb)beta3 T562N mediated cell adhesion (40.5 +/- 3.8
      cells/field), while alpha(IIb)beta3 wt did not (5.3 +/- 1.4 cells/field, P <
      0.001), allowing to discriminate the efficiency of each receptor. Similar
      findings were observed for adhesion to VWF. Complete inhibition of cell adhesion
      to fibrinogen was achieved with 800 microM fibrinogen gamma-chain dodecapeptide
      [HHLGGAKQAGDV (H12)], while Arg-Gly-Asp-Ser (RGDS) peptide (10-1000 microM)
      induced a dose-dependent cell detachment. These results suggest that the H12
      motif allows initial attachment, in contrast to the RGDS site, which strengthens
      the stability of adhesion. Interestingly, compared with wt, a 10-fold lower
      concentration of RGDS was required to reach a similar reduction of cell adhesion
      mediated by alpha(IIb)beta3 T562N. CONCLUSIONS: Our data show that
      alpha(IIb)beta3 activation is associated with a stabilization of integrin binding
      to fibrinogen or VWF under shear.

PMID- 16409473
TI  - The Ser219-->Gly dimorphism of the endothelial protein C receptor contributes to
      the higher soluble protein levels observed in individuals with the A3 haplotype.
AB  - The endothelial cell protein C receptor (EPCR) plays an important role in
      regulating blood coagulation and in activated protein C-mediated anti
      inflammatory and antiapoptotic processes. Recent studies reported that there are
      polymorphisms in the human EPCR gene. One of the polymorphisms (haplotype A3)
      results in substitution of the Ser at residue 219 with Gly in the transmembrane
      domain. This haplotype is associated with increased plasma levels of soluble EPCR
      and is a candidate risk factor for thrombosis. We established stable cell lines
      expressing either the EPCR A1 (Ser at residue 219) or A3 (Gly at residue 219)
      haplotype. Both constitutive and PMA-stimulated shedding are five- to sevenfold
      higher in the A3 cell line than the A1 cell line. We also isolated human
      umbilical vein endothelial cells (HUVEC) from A1/A1 or A1/A3 origins. PMA
      stimulated shedding is fourfold higher in HUVEC derived from A1/A3 origin than
      from A1/A1 origin. After PMA treatment, the rate of human protein C activation
      decreased 36% in HUVEC derived from A1/A3 origin, while it only decreased 18% in
      HUVEC derived from A1/A1 origin. These results indicate that the A3 haplotype
      does promote cellular shedding in either 293 or endothelial cells and therefore
      is likely directly contributory to the higher soluble EPCR levels seen in
      patients carrying this haplotype.

PMID- 16409476
TI  - Discovery of thrombin activatable fibrinolysis inhibitor (TAFI).

PMID- 16409481
TI  - The regulation of endothelial VWF secretion by nitric oxide: is it physiological?

PMID- 16409475
TI  - Inhibition of 5-hydroxytryptamine receptor prevents occlusive thrombus formation
      on neointima of the rabbit femoral artery.
AB  - BACKGROUND: Thrombus propagation on disrupted plaque is a major cause of acute
      coronary events and serious complication after coronary intervention. 5
      Hydroxytryptamine (5-HT) is a potent vasoactive and platelet-aggregating
      substance that is predominantly mediated by 5-HT2A receptor. However, the roles
      of 5-HT2A receptor in occlusive thrombus formation on disrupted plaque remain
      obscure. OBJECTIVE: We investigated the role of 5-HT2A receptor in thrombus
      formation using a rabbit model of repeated balloon-injury. METHODS: Three weeks
      after a first balloon-injury of the femoral arteries, luminal diameter,
      neointimal growth, and vasoconstriction by 5-HT in vitro were examined. Thrombus
      propagation and the role of 5-HT2A receptor after a second balloon-injury were
      evaluated using sarpogrelate, a selective 5-HT2A receptor antagonist. RESULTS:
      Three weeks after the first balloon-injury, luminal stenosis was evident in the
      femoral arteries, where the neointima expressed tissue factor and 5-HT2A
      receptor. The hypercontractile response of the stenotic arteries to 5-HT was
      significantly reduced by sarpogrelate. Balloon-injury of the neointima with
      substantially reduced blood flow promoted the formation of occlusive thrombus
      that was immunoreactive against glycoprotein IIb-IIIa, 5-HT2A receptor and
      fibrin. Intravenous injection of sarpogrelate significantly inhibited ex vivo
      platelet aggregation induced by adenosine 5'-diphosphate, thrombin and collagen
      alone as well as with 5-HT, and significantly prevented occlusive thrombus
      formation in vivo. CONCLUSIONS: The 5-HT2A receptor appears to play a crucial
      role in occlusive thrombus formation in diseased arteries via platelet
      aggregation and vasoconstriction. Inhibition of 5-HT2A receptor might help reduce
      the onset of acute coronary events and of acute coronary occlusion after the
      intervention.

PMID- 16409482
TI  - The reactivity of paired plasma and serum samples are comparable in the
      anticardiolipin and anti-beta2-glycoprotein-1 ELISAs.

PMID- 16409483
TI  - A novel compound heterozygous mutation in the F13A gene causing hereditary factor
      XIII deficiency in a Chinese family.

PMID- 16409484
TI  - Prophylaxis of venous thromboembolism in general and gynecologic day surgery in
      The Netherlands.

PMID- 16409485
TI  - Resistance to annexin A5 binding and anticoagulant activity in plasmas from
      patients with the antiphospholipid syndrome but not with syphilis.

PMID- 16409486
TI  - Protein S binding to phospholipids: evaluation of eight variants of recombinant
      human protein S from the PROSIT study.

PMID- 16409487
TI  - Fatty acid ethyl ester, a non-oxidative ethanol metabolite, reverses the
      inhibitory effect of ibuprofen on platelet aggregation.

PMID- 16409488
TI  - Deficiency of thrombospondin-1 in mice does not affect adipose tissue
      development.

PMID- 16409489
TI  - Accuracy and safety of pretest probability assessment of deep vein thrombosis by
      physicians in training using the explicit Wells clinical model.

PMID- 16409490
TI  - No significant improvement in diagnostic specificity of an anti-PF4/polyanion
      immunoassay with use of high heparin confirmatory procedure.

PMID- 16409491
TI  - More on: Pathogenic antibodies to coagulation factors. Part II: Fibrinogen,
      prothrombin, thrombin, factor V, factor XI, factor XII, factor XIII, protein C
      and von Willebrand factor.

PMID- 16409492
TI  - More on: Discovery of alpha2-plasmin inhibitor and its congenital deficiency.

PMID- 16409493
TI  - More on: The role of thrombin in gliomas.

PMID- 16409495
TI  - More on: Platelet count and the use of recombinant factor VIIa for the treatment
      of bleeding complications after hematopoietic stem cell transplantation.

PMID- 16409496
TI  - Superficial thrombophlebitis of the legs: still a lot to learn. A rebuttal.

PMID- 16409498
TI  - Further evidence that fibrillar collagen is unable to promote platelet shape
      change and aggregation in the absence of secondary agonists. A rebuttal.

PMID- 16409501
TI  - Re: Motivational interviewing as a strategy to increase families' adherence to
      treatment regimens.

PMID- 16409503
TI  - Untangling the health disparities of teen pregnancy.
AB  - PURPOSE: The purpose of this secondary analysis is to determine whether a
      developmental maturity model differentially predicts pregnancy for African
      American, Puerto Rican, and Mexican inner-city teens. DESIGN AND METHODS: This is
      a secondary analysis of data from a case control study that tested a model of
      developmental maturity and teen pregnancy with 183 pregnant and never-pregnant
      pairs of inner-city teens matched on age, ethnicity, and freshman cohort.
      RESULTS: The models differentially predict pregnancy for the separate ethnic
      groups, with sexual behaviors being the most important factors regardless of
      ethnicity. PRACTICE IMPLICATIONS: The health disparities of teen pregnancies may
      not decrease unless patterns of dating/sexual behaviors are reversed.

PMID- 16409502
TI  - Moving beyond the trickle-down approach: addressing the unique disparate health
      experiences of adolescents of color.
AB  - PURPOSE: Health disparities in adults have received significant attention and
      research, yet the healthcare experiences of adolescents of color have been
      ignored. The purpose of this paper is to identify the shortcomings of our state
      of knowledge regarding adolescent health disparities and argue for the use of an
      inter-sectional, contextually embedded understanding of healthcare experiences.
      CONCLUSIONS: To understand health disparities, deficit-based models should be
      replaced with the framework proposed in this paper. PRACTICE IMPLICATIONS: Using
      the proposed model in practice will aid in identifying and preventing the health
      disparities experienced by adolescents of color.

PMID- 16409504
TI  - Being healthy: voices of adolescent women who are parenting.
AB  - PURPOSE: The purpose of this ethnography was to explore how adolescent women who
      are parenting describe what "being healthy" means to them and how they define
      their health needs. METHODS: In addition to traditional ethnographic methods of
      interviewing and participant observation, photovoice was utilized. RESULTS:
      Women's definitions of "being healthy" were grouped into three categories: (1)
      "taking care of my body," (2) "not being stressed out," and (3) "having what you
      need." PRACTICE IMPLICATIONS: The findings of this research study suggest that
      healthcare professionals should consider adolescent mothers knowledgeable actors
      of their own lives and move beyond current strategies to concentrate on issues,
      such as socioeconomic contexts, that hinder the health and nutrition of these
      young women.

PMID- 16409505
TI  - Parent-child communication processes: preventing children's health-risk behavior.
AB  - PURPOSE: Review individual, family, and environmental factors that predict health
      risk behavior among children and to propose parent-child communication processes
      as a mechanism to mediate them. CONCLUSIONS: Improving parent-child communication
      processes may: reduce individual risk factors, such as poor academic achievement
      or self-esteem; modify parenting practices such as providing regulation and
      structure and acting as models of health behavior; and facilitate discussion
      about factors that lead to involvement in health-risk behaviors. PRACTICE
      IMPLICATIONS: Assessment strategies to identify youth at risk for health-risk
      behavior are recommended and community-based strategies to improve communication
      among parents and children need development.

PMID- 16409506
TI  - Ask the expert. Sexual health education disparities in Asian American
      adolescents.

PMID- 16409507
TI  - Collaborative practice. Undertreatment of pain and fears of addiction in
      pediatric chronic pain patients: how do we stop the problem?

PMID- 16409508
TI  - Scientific inquiry. (Re)Examining health disparities: critical social theory in
      pediatric nursing.

PMID- 16409509
TI  - Family-centered care. Decreasing health disparities.

PMID- 16409510
TI  - Chewing-side determination of three food textures.
AB  - Food texture affects chewing movement but it is not known if it also affects the
      chewing-side pattern. This study determined the chewing sides of three test foods
      with different textures during habitual chewing. Twenty healthy dental students
      (aged 20-24 years) chewed pieces of pork jerky, fresh asparagus and almonds on
      two separate sessions (1 week apart). In each session, each subject chewed 30
      food specimens, 10 of the same food type, until swallowing while a video camera
      recorded the displacement of the chin with respect to the other two reference
      points vertically marked along the facial midline. A slow-speed video playback
      was used to identify the chewing side of each cycle. The chewing-side pattern
      (right preference, left preference, no preference) in each individual was
      determined statistically. The results showed that overall, 11 subjects did not
      have any side preference whereas six and three subjects preferred to chew on
      right or left sides respectively. The chewing-side pattern remained unchanged
      between three food types in about half of the subjects. When the same food was
      compared between 2 days, the chewing-side pattern of almonds was shown to be most
      reproducible (18 subjects). Unidentified cycles with little or no lateral
      displacement, labelled as bilateral, were observed more frequently near the end
      of the chewing sequence with more occurrences in almonds and jerky than asparagus
      (P < 0.01). It was suggested that chewing-side preference is not a fixed
      characteristic. Food texture seemed to influence the side preference and also the
      occurrence of bilateral cycles.

PMID- 16409511
TI  - Effect of palate covering on bolus-propulsion time and its contributory factors.
AB  - The aim of this study was first to investigate whether the covering of the
      palatal mucosa with a denture base affects or not the bolus-propulsion time, and
      second if there was such an effect then investigate the possible contributory
      factors which have influence on the propulsion time. The propulsion time was
      measured in 21 young normal edentulous subjects under five different conditions:
      a complete palatal covering, non-covered palate, anterior palatal covering,
      posterior palatal covering and surface anaesthetized palate. As possible
      contributory factors palatal morphometric parameters, as well as tongue pressure
      were also measured. The data were analysed on the following way: changes when the
      palate was complete covered and non-covered, effects of sensation reduction after
      topic anaesthesia, effects of differences in the covering site, effects of
      palatal morphometric parameters and effects of tongue pressure. Ten subjects
      exhibited significant differences in the propulsion time when comparing the data
      between the complete palatal covering and the non-covered palate condition
      (change group). Eleven subjects did not show changes (unchanged group). Effects
      in the propulsion time were also recognized with posterior palatal covering
      palate and superficially anaesthetized palate. With regard to the tongue
      pressure, significant differences during swallowing were observed. These results
      indicated that the bolus propulsion time into the oropharynx was affected by the
      palatal covering in some subjects. Moreover, the sensation in the posterior
      region of the hard palate, as well as the tongue pressure were also factors which
      affected the propulsion time during swallowing.

PMID- 16409512
TI  - Epidemiological evaluation of the multifactorial aetiology of abfractions.
AB  - The purpose of this study was to determine risk indicators for the aetiology of
      abfractions (cervical wedge-shaped defects) on teeth using dental and medical
      variables obtained in a population-based sample of the cross-sectional
      epidemiological 'Study of Health in Pomerania' (SHIP). Medical history, dental,
      and sociodemographic parameters of 2707 representatively selected subjects 20-59
      years of age with more than four natural teeth were checked for associations with
      the occurrence of abfractions using a two-level logistic regression model on a
      tooth and a subject level. The estimated prevalence of developing abfractions
      generally increased with age. The following independent variables were associated
      with the occurrence of abfractions: buccal recession of the gingiva, odds ratio
      (OR) = 6.7; occlusal wear facets of scores 1, 2 and 3, OR = 1.5, 1.9, 1.9; tilted
      teeth, OR = 1.4; inlays, OR = 1.6; toothbrushing behaviour, OR = 1.9 to 2.0 (two
      and three times a day versus once a day). First premolars had the highest
      estimated risk for developing abfractions, followed by the second premolars.
      Maxillary and mandibular teeth behaved similarly in terms of abfractions, with
      the exception of mandibular canines, which had a much lower estimated risk of
      incurring abfractions than did maxillary canines. The results of this analysis
      indicated that abfractions are associated with occlusal factors, like occlusal
      wear, inlay restorations, altered tooth position and tooth brushing behaviour.
      This study delivers further evidence for a multifactorial aetiology of
      abfractions.

PMID- 16409513
TI  - Hardness of enamel exposed to Coca-Cola and artificial saliva.
AB  - The purpose of this study was to determine the rate of change in indentation
      hardness of enamel in permanent teeth exposed to Coca-Cola. In a further
      experiment, the ability of a commercially available artificial saliva to
      remineralize enamel treated with Coca-Cola was tested. Ten enamel specimens were
      randomly chosen to be treated with Coca-Cola (experimental groups) and seven with
      water (control group). The fluids were applied for 1, 2, 3 h and overnight (15
      h), washed off with a few drops of water and the moist enamel indentation
      hardness tested after each interval. With Coca-Cola treatment, the mean enamel
      hardness was 92.6% (s.d. = 7.9) of the original baseline hardness after 1 h,
      93.25% (s.d. = 10.15) after 2 h, 85.7% (s.d. = 12.03) after 3 h and 80.3% after
      15 h. The mean indentation hardness of control specimens treated with water was
      108.7% (s.d. = 16.09) of the original hardness after 1 h, 99.09% (s.d. = 18.98)
      after 2 h, 98.97% (s.d. =11.24) after 3 h and 98.42% (s.d. = 22.78) after 15 h.
      In a separate experiment, the hardness of 9 enamel specimens was tested, as
      previously described, before and after treatment with Coca-Cola overnight and
      again after application of artificial saliva for 3 min. Coca-Cola reduced the
      mean indentation hardness of enamel in the teeth, but the hardness was partially
      restored with artificial saliva (Salivart) and increased by 18% from the
      demineralized enamel hardness.

PMID- 16409514
TI  - Shade selection performed by novice dental professionals and colorimeter.
AB  - The objective of this study was to test inter-observer variability in shade
      selection for porcelain restorations, using three different shade guides: Vita
      Lumin Vacuum, Vita 3D-Master and Procera. Nineteen young dental professionals
      acted as observers. The results were also compared with those of a digital
      colorimeter (Shade Eye Ex; Shofu, Japan). Regarding repeatability, no significant
      differences were found between the three shade guides, although repeatability was
      relatively low (33-43%). Agreement with the colorimetric results was also low (8
      34%). In conclusion, shade selection shows moderate to great inter-observer
      variation. In teaching and standardizing the shade selection procedure, a digital
      colorimeter may be a useful educational tool.

PMID- 16409515
TI  - Association of candidal activity with denture use and salivary flow in symptom
      free adults over 60 years.
AB  - The purpose of this study was to examine the amount of palatal mucosa Candida
      species associated with denture use and stimulated salivary flow in symptom-free
      adults over 60 years. The subjects were 351 (189 men and 162 women) independently
      living elderly people with a mean age of 66.7 +/- 4.3 (SD) years. Candidal
      activity of palatal mucosa was evaluated by the pH change in the medium that was
      associated with the acid production of the yeast. Subjects whose stimulated
      salivary flow rate was less than 0.5 ml/min were placed in the hyposalivation
      group. A multiple logistic regression analysis was used to determine if an
      independent variable was statistically significant after controlling for other
      variables. Candidal activity of the palatal mucosa was significantly associated
      with the dental status of the maxillae (Kruskal-Wallis test, P < 0.001), but was
      not significantly associated with age or drug intake. In maxillary denture
      wearers, Candidal activity of palatal mucosa had a significantly positive
      correlation with candidal activity of tissue fitting surfaces of maxillary
      dentures (r = 0.806, P < 0.001). A multiple logistic regression analysis showed
      that high candidal activity of the palate was significantly associated with being
      male and wearing maxillary removable dentures. Stimulated salivary flow rate was
      likely to be negatively related to high candidal activity (P = 0.07). This study
      suggests that the activity of Candida species in the oral cavity is associated
      with the wearing of removable dentures and stimulated salivary flow, independent
      of age or gender even in the relatively healthy elderly.

PMID- 16409516
TI  - The vibratory characteristics of obturators with different bulb height and form
      designs.
AB  - The aim of the present study was to investigate whether the vibratory
      characteristics of obturator prostheses are affected by bulb design, i.e.: the
      hollow or buccal flange type, and different lateral and medial bulb heights.
      Buccal flange and hollow bulb obturator prostheses were fabricated with two
      different lateral bulb wall heights and two different medial bulb wall heights.
      Ultimately, eight obturator prostheses were prepared for evaluation of their
      vibratory characteristics. The frequency-response functions were recorded on an
      FFT analyzer to identify their vibratory characteristics. A transient response
      simulation was carried out in which an impact was applied to the non-defect side.
      The decay rate, damping time and maximum amplitude of the retainers were
      statistically analysed by anova with Scheffe's test (P < 0.05). The decay rate of
      every buccal flange type was higher and damping time was shorter than those of
      every hollow type, except between a pair with low lateral and low medial bulb
      walls. The maximum amplitude values of four obturators with low medial bulb walls
      were significantly lower than those of four obturators with high medial walls.
      The buccal flange obturator prosthesis with high lateral and low medial walls
      showed the maximum decay rate and the minimum amplitude of the retainers on
      molars. Vibration analysis suggests that a buccal flange obturator prosthesis
      with high lateral and low medial walls is preferable.

PMID- 16409517
TI  - A new approach to define defect extensions of endodontically treated teeth: inter
      and intra-examiner reliability.
AB  - For endodontically treated teeth, there are no standardized measures available to
      define the extent of loss in tooth substance prior to final restoration. In this
      study, defect size was classified and the applicability of the classification was
      tested related to the inter- and intra-examiner reliability. For classification,
      three parameters were investigated: (i) remaining tooth substance in the vertical
      dimension (level A-D, aspect I), (ii) remaining tooth substance as regarded
      horizontally (mm; bucco-lingual and mesio-distal, aspect II), and (iii) size of
      the orifice (mm; aspect III). Four non-calibrated or (pre-trained) examiners were
      asked to gauge and classify 20 casts of clinically broken down teeth. The
      measurements were repeated twice every alternative week giving three separate
      readings. Inter-examiner reliability was determined at weeks 1, 3 and 5. The
      intra-examiner reliability was compared between readings 1 and 2, 1 and 3, and 2
      and 3. As statistical tests, intra-class correlation (ICC) and Cohen's kappa
      (weighted) were used at a significance level of P < 0.05. Inter- and intra
      examiner reliability for ordinal data (aspect I) revealed, with one exception,
      'moderate' to 'very good' evaluations. Inter- and intra-examiner reliability
      (ICC) of metric data of aspect II and III was primarily 'excellent'. It may be
      concluded that the newly developed classification could be applied as an
      appropriate and reproducible method to define defect extension in endodontically
      treated teeth.

PMID- 16409518
TI  - Measurement of clinical wear of two packable composites after 6 months in
      service.
AB  - Original large-particle composites exhibited poor wear characteristics. With the
      packable composites, there has been a reintroduction of large particles. The
      clinical wear characteristics of such packable composites are relatively unknown.
      The purpose of this study was to compare wear between two types of packable
      composites: Alert (Jeneric Pentron) and Surefil (Dentsply Caulk). Each material
      was compared with and without a surface sealant. Fifty-two subjects were
      included. Subjects had to have two to four eligible teeth, be 21 years of age, in
      good health and in need of moderate to large class 2 restorations on molars,
      and/or a two-surface class 1 on molars. Wear was assessed, using the Moffa
      Lugassy (ML) scale, by evaluating stone models made from polyvinyl siloxane (PVS)
      impressions taken at baseline and 6 months. Rating was done by four calibrated
      examiners using a forced consensus model. The use of a surface sealant with Alert
      significantly reduced the median wear rate at 6 months compared with that of the
      SureFil restorations.

PMID- 16409519
TI  - Effects of the Nd:YAG laser, air-abrasion, and acid-etchant on filling materials.
AB  - The purpose of this study was to determine any inadvertent effects of the
      neodymium: yttrium-aluminium-garnet (Nd:YAG) laser, air-abrasion, and ortho
      phosphoric acid on some conventionally used dental filling materials [amalgam,
      composite resin, compomer, glass-ionomer cement (GIC), and ceromer], when they
      were used for purposes of margin etching and assessed according to standard
      enamel etching parameters using a total of five fillings. The surfaces of the
      filling materials were polished. One sample from each material group was exposed
      to laser (at 0.75 J, 15 pps) and air abrasion (with Al-oxide powder, 60 psi) for
      2 s and to the 37% ortho-phosphoric acid for 60 s. The exposed materials were
      examined under Scanning Electron Microscopy (SEM). After laser treatment most
      specimens showed recrystallized areas, the GIC surface being the most affected.
      There were some pores and cavities on the amalgam surface following laser
      treatment. The abraded surfaces showed mechanical abrasions. The acid etchant
      showed the least effect. During the application of laser or air-abrasion, the
      adjacent tooth or filling surface must be protected or the dentist must be
      careful.

PMID- 16409520
TI  - Yield strength of zirconia and glass fibre-reinforced posts.
AB  - The aim of this in vitro study was to evaluate the yield strengths of glass fibre
      reinforced composite (FRC) posts and zirconia dioxide ceramic (ZDC) posts.
      Tapered glass FRC posts (DentinPost) and ZDC posts (Cerapost) of three sizes in
      diameter (ISO 50, 90, 110) were used for bending tests. Conventional
      prefabricated titanium posts of the same sizes served as control groups. The 0.2%
      yield strengths (R(0.2)) were tested on a universal testing machine. As zirconia
      posts fractured before they were yielded 0.2%, the fracture strength instead of
      the yield strength was recorded for these posts. One-way and two-way anova and
      Bonferroni-Dunn's multiple comparison tests were performed for the statistical
      analysis. The mean 0.2% yield strengths of the posts were 27 +/- 1 N for glass
      fibre-reinforced posts and 58 +/- 4 N for zirconia posts of ISO 50 (control
      group: 54 +/- 3 N). For ISO 90 yield strengths of 52 +/- 4 N for glass fibre
      reinforced posts, 117 +/- 20 N for zirconia posts and 117 +/- 11 N for the
      control group were obtained. For ISO 110 mean yield strengths amounted to 73 +/-
      5 N for glass fibre-reinforced posts, 166 +/- 23 N for zirconia posts and 141 +/-
      12 N for the control group. Significantly higher yield strength was recorded for
      the zirconia and the titanium posts compared with the glass fibre-reinforced
      posts for the tested ISO sizes.

PMID- 16409521
TI  - In vitro differences of stress concentrations for internal and external hex
      implant-abutment connections: a short communication.
AB  - The aim of this study was to clarify the difference in the stress distribution
      patterns between implants with external-hex or internal-hex connection systems
      using in vitro models. Three 13 mm fixtures with external-hex and internal-hex
      connections were installed into an acrylic bone analogue. One piece abutments of
      7 mm height was connected. Strain gauges were attached to the abutment surface,
      and the cervical and fixture tip areas of the bone analogue surface. Vertical and
      horizontal load applied was 30 N. Data were normalized for each model by
      obtaining values relative to the sum of the three values. Almost the same force
      distribution pattern was found under vertical load in both systems. Fixtures with
      external-hex showed an increase in strain at the cervical area under horizontal
      load, while in internal-hex fixtures the strain was at the fixture tip area.
      Within limitations of our model study, it was suggested that fixtures with
      internal-hex showed widely spread force distribution down to the fixture tip
      compared with external hex ones.

PMID- 16409522
TI  - Historical aspects of inhalation anesthesia in children: ether and chloroform.

PMID- 16409524
TI  - Performance of a novel pressure release valve for cuff pressure control in
      pediatric tracheal tubes.
AB  - BACKGROUND: Acute and chronic hyperinflation of tracheal tube cuffs represents a
      persistent risk factor for airway damage in children when cuffed tracheal tubes
      are used. In order to overcome this particular risk, a cuff pressure (CP) pop-off
      valve has been designed to avoid CP exceeding 20 cmH(2)O. METHODS: The
      performance of the novel pop-off valve has been evaluated in an in vitro set-up
      during slow and rapid air insufflation by a syringe or a CP manometer or
      inadvertent compression of the cuff pilot balloon while measuring cuff and
      tracheal wall pressure (WP) in ID 3.0 mm cuffed tracheal tubes. Steady-state
      performance was evaluated during nitrous oxide exposure of tracheal tube cuffs
      (ID 3.0 mm). RESULTS: The novel CP pop-off valve avoided cuff hyperinflation
      during rapid air volume changes and showed reliable performance during steady
      state nitrous oxide exposure to the tube cuff. CONCLUSIONS: These preliminary
      results show that the CP pop-off valve limits the effect of rapid, potentially
      dangerous manual cuff inflation maneuvers and reliably prevents CP exceeding the
      predetermined level of 20 cmH(2)O when exposed to nitrous oxide.

PMID- 16409523
TI  - Parents' willingness to pay for diminishing children's pain during blood
      sampling.
AB  - BACKGROUND: Blood sampling is a frequent medical procedure, very often considered
      as a stressful experience by children. Local anesthetics have been developed, but
      are expensive and not reimbursed by insurance companies in our country. We wanted
      to assess parents' willingness to pay (WTP) for this kind of drug. PATIENTS AND
      METHODS: Over 6 months, all parents of children presenting for general (GV) or
      specialized visit (SV) with blood sampling. WTP was assessed through three
      scenarios [avoiding blood sampling (ABS), using the drug on prescription (PD), or
      over the counter (OTC)], with a payment card system randomized to ascending or
      descending order of prices (AO or DO). RESULTS: Fifty-six responses were
      collected (34 GV, 22 SV, 27 AO and 29 DO), response rate 40%. Response
      distribution was wide, with median WTP of 40 for ABS, 25 for PD, 10 for OTC,
      which is close to the drug's real price. Responses were similar for GV and SV.
      Median WTP amounted to 0.71, 0.67, 0.20% of respondents' monthly income for the
      three scenarios, respectively, with a maximum at 10%. CONCLUSIONS: Assessing
      parents' WTP in an outpatient setting is difficult, with wide result
      distribution, but median WTP is close to the real drug price. This finding could
      be used to promote insurance coverage for this drug.

PMID- 16409525
TI  - Cuff filling volumes and pressures in pediatric laryngeal mask airways.
AB  - BACKGROUND: Hyperinflation of LMA cuffs carries the risk of airway morbidity by
      exerting pressure on laryngeal and pharyngeal structures. Cuff hyperinflation in
      LMAs can result from nitrous oxide diffusion into the LMA cuff and from
      deliberate manual cuff inflation. METHODS: In an in vitro set up, maximum
      recommended cuff filling volumes for size 1, 1.5, 2, 2.5, 3 disposable LMAs from
      different manufacturers [SoftSeal LMA (Portex); Unique LMA (Intavent); Marshall
      LAD, LaryngoSeal (Tyco)] and reusable Classic and ProSeal LMAs (Intavent) were
      inflated into completely emptied LMA-cuffs and into LMA-cuffs at resting volume.
      Cuff pressures were measured using a cuff manometer. Experiments were performed
      eight times using two exemplars of each brand/size. RESULTS: Maximum recommended
      cuff filling volumes for pediatric LMAs resulted in hyperinflation (cuff pressure
      >60 cmH(2)O) in almost all LMAs, starting with emptied cuff. Starting from
      resting cuff volume, the maximum recommended inflation volume resulted in cuff
      pressures of >120 cmH(2)O in all LMAs and sizes except in the ProSeal size 3 (101
      +/- 1 cmH(2)O). CONCLUSIONS: Since the volume of air which is effectively
      required depends on several factors and varies between patients, the cuffs should
      be inflated only with the minimum volume of air required to form an effective
      seal with the respiratory and gastrointestinal tracts and the cuff pressure
      should be controlled.

PMID- 16409526
TI  - Perioperative care of the child with arthrogryposis.
AB  - BACKGROUND: Arthrogryposis multiplex congenita (AMC) is a congenital symptom
      complex characterized by multiple joint contractures. AMC results from fetal
      akinesia due to extrinsic factors (oligohydramnios) or primary neurogenic or
      myopathic conditions of the fetus. METHODS: We retrospectively reviewed our
      perioperative experience in 12 patients with AMC. RESULTS: Intraoperative issues
      noted in our patients included difficulties with peripheral IV placement (n = 3),
      difficult tracheal intubation (n = 4), and intraoperative hyperthermia (n = 4).
      Difficulties with peripheral IV placement were more common in younger patients
      (2.3 +/- 0.6 vs 9.2 +/- 3.5 years). Although easy bag-valve-mask ventilation was
      present in all 12 patients, difficulty with tracheal intubation was noted in four
      patients. In these four patients, the airway was secured using an LMA (n = 3) or
      a facemask (n = 1). The patients in whom difficulties with tracheal intubation
      were encountered were older than patients in whom no difficulties were noted
      (11.0 +/- 2.9 vs 5.8 +/- 3.9 years). Four patients developed intraoperative
      temperatures > or =37 degrees C; however, there was no evidence of hypercarbia or
      tachycardia suggestive of malignant hyperthermia. Postoperative issues included
      stridor (n = 2) and postoperative atelectasis (n = 3). CONCLUSIONS: The
      perioperative care of patients with AMC should consider not only the physical
      manifestations of the disease process, but also the implications of the
      underlying neuromuscular disease. The most common perioperative issues included
      difficulties with airway management, problematic intravenous access, and
      intraoperative hyperthermia.

PMID- 16409527
TI  - Leigh syndrome: anesthetic management in complicated endoscopic procedures.
AB  - BACKGROUND: Leigh's syndrome, a disorder of infancy and childhood, is
      characterized by gray matter degeneration and focal brainstem necrosis. It
      presents with special clinical features such as developmental delay, nervous
      system dysfunction, respiratory abnormalities, and hypertrophic cardiomyopathy
      that can be a real challenge to the anesthesiologist. Anesthesia or sedation has
      rarely been reported in patients with Leigh disease. We report our experience in
      sedating five children with Leigh syndrome in seven procedures undertaken in the
      endoscopy suite (outside the operating room). METHODS: Five children with Leigh
      disease, three girls and two boys, have been referred to us for percutaneous
      endoscopic gastrostomy (PEG) insertion and or replacement (a total of seven
      procedures). The average age was 2.6 years with a range of 4 months to 6 years.
      Informed consent was obtained from the patient's parents or guardian. An
      anesthesia machine, scavenging system, O(2) source and routine monitoring were
      available. Sedation was accomplished with propofol intravenous (i.v.) (0.5-1 mg x
      kg(-1)) maintained with a propofol infusion (50-100 microg x kg(-1) x min(-1)).
      The spontaneously breathing patients received oxygen through an oxygen facemask
      during the procedure and afterwards recovery was managed in the gastroenterology
      unit. RESULTS: All the children underwent the procedure without complications.
      One patient developed transient desaturation (SpO(2) 80%) for a few seconds. Body
      temperature, heart rate, arterial blood pressure, O(2) saturation and endtidal
      CO(2) were stable during the endoscopies. No special post-procedure management
      was required; the patients woke up at the end of the endoscopy and were able to
      drink and eat as usual. CONCLUSIONS: This rare mitochondrial disease presents
      unique management problems to the anesthesiologist when using general anesthesia.
      Our patients were managed appropriately before endoscopy and underwent the
      procedure under deep sedation. No complications occurred. We concluded that deep
      sedation in the endoscopy suite was safe in this small series of patients with
      this rare disease.

PMID- 16409528
TI  - Spinal anesthesia in children with isobaric local anesthetics: report on 307
      patients under 13 years of age.
AB  - BACKGROUND: Spinal anesthesia in expert hands is an excellent method for children
      for appropriate surgery. The aim of this study was to evaluate the effects of
      spinal anesthesia with isobaric solutions in 307 consecutive cases from May 2001
      to August 2002. METHODS: In this prospective study, 307 patients from 0 to 12
      years of age were scheduled for spinal anesthesia with enantiomeric mixture of
      bupivacaine (S75 : 25R) 0.5% or racemic bupivacaine 0.5% or lidocaine 2% without
      glucose, for surgery compatible with the technique. The following were assessed:
      latency of analgesia, motor block, maximum length and duration of sensory
      blockade, cardiovascular changes, incidence of headache or transient neurological
      symptoms and cost. RESULTS: The onset of sensory block occurred at 2.36 +/- 0.95
      min. Duration of surgery was 1.29 +/- 0.83 h and the duration of stay in the
      postanesthesia care unit was 39.72 +/- 26.84 min. The highest level of analgesia
      ranged from T(9) to T(4) (mean T(6)). Onset of motor block was <2 min in all
      children and each had a modified Bromage score of 3 at the beginning of the
      surgery. At the end of the surgery 9% had score 3, 16%, score 2, 46%, score 1 and
      29%, zero. Seventy five percent of all patients recovered from motor block 1 or
      zero at the end of the surgery. Patients older than 1 year were able to walk in
      3.79 +/- 0.73 h. There was no case of oxygen desaturation. Hypotension and
      bradycardia occurred in one patient. Spinal anesthesia failed in five patients.
      Three children developed postdural puncture headache (PDPH), the youngest aged 2
      years. PDPH in all three was mild or moderate. Transient radicular symptoms were
      not observed. The final cost of the spinal anesthesia was R dollars 49.00
      compared with a mean cost of general anesthesia of R dollars 105.00. CONCLUSIONS:
      Spinal anesthesia continues to gain acceptance as an alternative to general
      anesthesia in children. There has also been an increased use of spinal anesthesia
      for other surgical procedures including lower extremity orthopedic procedures as
      well as specific surgery procedures above the umbilicus and in patients past the
      neonatal period. Spinal anesthesia in children is a special method suitable for
      use only by anesthesiologists, expert in administering spinal anesthesia for
      adults. It was 54% less than the cost of general anesthesia.

PMID- 16409529
TI  - A prospective randomized blinded study of the effect of intravenous fluid therapy
      on postoperative nausea and vomiting in children undergoing strabismus surgery.
AB  - BACKGROUND: Nausea and vomiting is a common postoperative complication that often
      necessitates the use of antiemetic agents. METHODS: In a prospective, randomized,
      double blind trial, the effect of perioperative fluid administration on
      postoperative adverse outcomes following anesthesia was studied. One hundred
      children undergoing strabismus repair were randomly assigned to receive 10 ml x
      kg(-1) x h(-1) (control group) or 30 ml x kg(-1) x h(-1) (superhydration group)
      of lactated Ringer's solution during the operation. During the first 24 h
      postoperatively, nausea and vomiting, thirst, pain, and fever were evaluated.
      RESULTS: Groups were similar with respect to demographic data, surgical
      procedures and baseline hemodynamic variables. In the first 24 h postoperatively,
      nausea and vomiting occurred in 27 patients (54%) of the control group and 11
      (22%) of patients in the superhydration group (P = 0.001). Comparison of the
      superhydration group with the control group also showed a statistically
      significant benefit of superhydration on postoperative thirst (P = 0.0002) and
      fever (P = 0.02). The differences in nausea and vomiting, thirst, and fever
      remained significant after adjustment for age, gender, weight, and duration of
      surgery. There was no significant difference between the two groups in
      postoperative pain. CONCLUSIONS: Intravenous superhydration administration is an
      inexpensive and safe therapy for reducing postoperative nausea and vomiting and
      discomfort.

PMID- 16409530
TI  - Tramadol for pain relief in children undergoing herniotomy: a comparison with
      ilioinguinal and iliohypogastric blocks.
AB  - BACKGROUND: Prevention of postoperative pain in children is one of the most
      important objectives of the anesthesiologist. Preoperative ilioinguinal and
      iliohypogastric nerve blocks have been widely used to provide analgesia in
      children undergoing herniorrhaphy. Tramadol is an analgesic with micro-opioid and
      nonopioid activity. In this study we compared the usage of intravenous tramadol
      with ilioinguinal and iliohypogastric nerve blocks for control of post
      herniorrhaphy pain in children aged 2-7 years. METHODS: Sixty patients were
      randomly allocated to two groups of thirty. One group received tramadol 1.5
      mg.kg(-1) i.v. before induction of general anesthesia and the other had an
      ilioinguinal and iliohypogastric nerve block with 0.5% bupivacaine (0.25 ml.kg(
      1)) before skin incision. We assessed pain using the Children's Hospital of
      Eastern Ontario Pain Scale and the Categorical Pain Scale. RESULTS: At 1, 4 and
      24 h after surgery the two groups had identical pain scores. At 2 and 3 h after
      surgery the tramadol group experienced significantly less pain (P < 0.05). The
      rescue drug for residual pain, was used equally in the two groups. None of the 60
      patients had respiratory depression but the tramadol group patients were found to
      have more episodes of nausea and vomiting (P < 0.05). CONCLUSIONS: We concluded
      that tramadol can have at least the same analgesic effect as that of ilioinguinal
      and iliohypogastric nerve blocks for post-herniorrhaphy pain in children, with
      even a superior effect at the time of maximal analgesia. We also highlight the
      troublesome side-effect of nausea and vomiting which brings into question the
      benefits of using this opioid that seems to lack respiratory depression.

PMID- 16409531
TI  - Atropine-induced lens extrusion in an open eye surgery.
AB  - A 2-month-old male baby undergoing penetrating keratoplasty (PKP) under general
      anesthesia developed bradycardia and a decrease in heart rate to 53 b x min(-1)
      when stay sutures were taken through the superior and inferior recti. A bolus of
      0.1 mg intravenous atropine resulted in tachycardia of up to 180-220 b x min(-1),
      which persisted for 35 min. After corneal trephination was performed the eyeball
      seemed to pulsate with the heartbeat. Spontaneous extrusion of the lens and
      vitreous occurred, which necessitated a lensectomy and vitrectomy in addition to
      PKP. The role of atropine in corneal transplant surgery is discussed here.

PMID- 16409532
TI  - Torsade de pointes during sevoflurane anesthesia in a child with congenital long
      QT syndrome.
AB  - We present a case of congenital long QT syndrome which developed torsade de
      pointes during sevoflurane anesthesia for implantation of an internal
      cardioverter-defibrillator. The diagnosis, implications and treatment are
      discussed.

PMID- 16409533
TI  - Anesthetic implications of Jacobsen syndrome.
AB  - Jacobsen syndrome (JS), also known as 11q-syndrome, is a congenital disorder
      associated with a deletion of the long arm of chromosome 11. Patients with JS
      characteristically exhibit multiple dysmorphic features, developmental delay,
      cardiac anomalies, and platelet abnormalities. Anesthetic issues related to the
      care of patients with JS concern airway management secondary to short neck,
      abnormal mouth shape and micrognathia/retrognathia, a high incidence of cardiac
      anomalies, and platelet dysfunction. Importantly, platelet abnormalities affect
      95% of reported JS patients and involve platelet number, size and function. Two
      children with JS who required open heart surgery are presented and anesthetic
      management issues discussed. These patients represent the first reports regarding
      the perioperative issues in caring for patients with JS.

PMID- 16409534
TI  - Anesthetic management of pial synangiosis and intracranial hemorrhage with a
      Fontan circulation.
AB  - We report the case of a 11-year-old girl with Moyamoya syndrome, who had
      undergone staged-repair of tricuspid atresia to a Fontan circulation, scheduled
      to undergo bilateral pial synangiosis. Surgery for the first hemisphere was
      complicated by intracranial hemorrhage requiring an emergency craniotomy. The
      case highlights the importance of understanding Fontan physiology and its
      interrelationship with the cerebral circulation in the setting of cerebrovascular
      insufficiency and raised intracranial pressure.

PMID- 16409535
TI  - Successful anesthetic management of a child with an extensive facial hemangioma
      and high output cardiac failure for placement of a central venous catheter.
AB  - A two-and-a-half-year-old female with an extensive facial and lingual hemangioma,
      associated high output cardiac failure, and a history of difficult intubation
      presented for central venous catheter (CVC) placement for vincristine
      chemotherapy. Anesthetic management of this complex case is presented and the
      complicating medical conditions are discussed.

PMID- 16409536
TI  - Anesthesia management in a young child with aromatic l-amino acid decarboxylase
      deficiency.
AB  - Aromatic l-amino acid decarboxylase (AADC) deficiency is characterized by an
      almost complete absence of sympathetic autoregulation, because of very low levels
      of circulating catecholamines. Here, we report the successful management of four
      consecutive anesthesia procedures in a young child presenting with AADC
      deficiency. Our experience suggests that, with appropriate anticipation of the
      potential autonomic disturbances, anesthesia, at least for minor surgical and
      diagnostic procedures, can be conducted safely in patients with AADC deficiency.

PMID- 16409537
TI  - Near-death experience in a boy undergoing uneventful elective surgery under
      general anesthesia.
AB  - Near-death experience (NDE) is a complex subjective experience, which may include
      affective elements such as a sense of peacefulness, paranormal components such as
      a sensation of floating out of the body, and a perception of being in a dark
      tunnel and seeing a brilliant light. It is usually reported to occur in
      association with a wide range of life-threatening situations, as for instance,
      cardiopulmonary resuscitation. We report on an episode of NDE that occurred in a
      12-year-old boy who underwent a general anesthesia for an elective uncomplicated
      surgery. To our knowledge, this is the first case of NDE in a child that has been
      reported in this context.

PMID- 16409538
TI  - Fatal marrow emboli in a pediatric patient having posterior spinal
      instrumentation for scoliosis repair.
AB  - This report describes the intraoperative course of a pediatric patient with
      neuromuscular scoliosis who died of massive fat and marrow emboli during
      posterior instrumentation for scoliosis surgery. In addition, the report
      describes the incidence and consequences of embolic events during spine surgery
      as well as the most common clinical sequelae. This patient's unique presentation
      is highlighted.

PMID- 16409539
TI  - Trial registration, the International Committee of Medical Journal Editors
      statement and pediatric journals.

PMID- 16409540
TI  - Right lung atelectasis during general anesthesia with laryngeal mask airway.

PMID- 16409541
TI  - Anesthesia in a child with pyruvate dehydrogenase deficiency.

PMID- 16409542
TI  - Anesthesia in an infant with uncorrected tetralogy of Fallot for transanal pull
      through for Hirschsprung's disease.

PMID- 16409543
TI  - Two hands, three sites: show me the vocal cords.

PMID- 16409544
TI  - VPCs during pediatric noncardiac surgery leading to the diagnosis of a coronary
      artery fistula.

PMID- 16409547
TI  - Report on the 4th Scientific Meeting of the Asian Society of Paediatric
      Anaesthesiologists, September 24-25 2005, in Singapore.

PMID- 16409545
TI  - Caudal catheters and ultrasound.

PMID- 16409548
TI  - Apical vulnerability to dendritic retraction in prefrontal neurones of ageing
      SAMP10 mouse: a model of cerebral degeneration.
AB  - The SAMP10 mouse is a model of accelerated ageing in which senescence is
      characterized by age-related atrophy of the cerebral cortex and limbic
      structures, poor learning and memory task performance with depressive behaviour
      and cholinergic and dopaminergic alterations. Here we studied age-related changes
      in the dendritic arbors and spine density of pyramidal cells in the medial
      prefrontal cortex of SAMP10 mice using a quantitative Golgi method. Dendrites of
      prefrontal neurones gradually retracted with ageing towards the soma with the
      relative preservation of overall complexity. Apical dendrites were much more
      severely affected than basal dendrites. The combined length of the apical
      dendrites and spine density were decreased by 45% and 55%, respectively, in mice
      at 12 months, compared with mice at 3 months of age. Immunohistochemical and
      immunoblot analyses indicated that expression of microtubule-associated protein
      (MAP) 2, a marker of dendrites, decreased in an age-related manner not only in
      the anterior cortex but also in the posterior cortex and olfactory structures in
      SAMP10 mice. Decreased expression of MAP2 mRNA caused the decrease in MAP2
      protein expression. These results suggest that retraction of apical, but not of
      basal dendrites, with a loss of spines in prefrontal neurones, appears to be
      responsible for poor learning and memory performance in aged SAMP10 mice. It is
      also suggested that age-related dendritic retraction occurs in a wide area
      including the entire cerebral cortex and olfactory structures.

PMID- 16409549
TI  - PECAM-1 and gelatinase B coexist in vascular cuffs of multiple sclerosis lesions.
AB  - In multiple sclerosis (MS), the matrix metalloprotease (MMP) gelatinase B/MMP-9
      and platelet endothelial cell adhesion molecule (PECAM)-1 have both been
      implicated in trans-endothelial infiltration of leucocytes into the brain, but
      their functional connection has not yet been investigated. We investigated the
      expression of gelatinase B and PECAM-1 in post mortem brains of MS patients by
      immunohistochemistry. Because increased soluble PECAM-1 serum levels have been
      observed in MS patients, we also tested in vitro whether this could be due to
      cleavage of PECAM-1 by gelatinase B or matrilysin-1/MMP-7. Constitutive
      expression of PECAM-1 was found on brain endothelial cells, whilst in active MS
      lesions cell-bound PECAM-1 was highly up-regulated on foamy macrophages in
      perivascular infiltrates and co-localized with gelatinase B. However, human THP-1
      monocyte-bound or soluble recombinant PECAM-1 were both resistant to proteolytic
      cleavage by gelatinase B or matrilysin-1 in vitro, as demonstrated by Western
      blot analysis and flow cytometry. These results suggest that PECAM-1 and
      gelatinase B may complement each other during the transmigration of the blood
      brain barrier by mononuclear cells.

PMID- 16409550
TI  - Lrrk2 R1441 substitution and progressive supranuclear palsy.
AB  - Mutation of the LRRK2 gene has been associated with autosomal dominant
      parkinsonism. An R1441C pathogenic substitution was identified in Family D, a
      large Western Nebraskan kindred, with four members demonstrating pleomorphic
      pathology at autopsy. One member of this family displayed tau pathology
      suggestive of progressive supranuclear palsy (PSP). To evaluate the influence of
      mutation at the R1441 residue in this disorder we screened a series of 242
      pathologically confirmed PSP cases. No evidence was found for the presence of a
      mutation at this codon in our series. These data would suggest that this Lrrk2
      variant does not contribute in susceptibility to PSP.

PMID- 16409551
TI  - Delayed spinocerebellar ataxia in transgenic mice expressing mutant ubiquitin.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease
      resulting from loss of Purkinje neurones within the cerebellum. The ubiquitin
      proteasome pathway (UPP) has been implicated in SCA1 but the role of proteolysis
      in the disease is still poorly understood. To further investigate this issue in
      vivo, genetic crosses were performed between an established mouse model of SCA1
      and novel strains expressing elevated levels of wild type or mutant isoforms of
      ubiquitin. The K48R mutant isoform of ubiquitin (a dominant negative inhibitor of
      proteolysis) was found to significantly delay the deterioration of Purkinje
      neurones as evidenced by behavioural, morphological, and molecular indicators.
      This delay was accompanied by stabilization of p300/CBP, transcriptional
      mediators whose abundance and activity would otherwise decline in the course of
      the SCA1 disease, and persistence of protein kinase C gamma (PKCgamma), a protein
      involved in Purkinje cell dendritic development that is mutated in one form of
      spinocerebellar ataxia. Whereas the stabilization of p300/CBP was found to occur
      at the post-translational level the modulation of PKCgamma was at the level of
      transcription. These results are consistent with transcriptional dysregulation as
      a key mechanism in neurodegeneration through loss of p300/CBP. Further, the
      results suggest that the UPP is a potentially useful target for the development
      of novel therapies for the treatment of neurodegenerative disease.

PMID- 16409552
TI  - Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix
      metalloproteinase-9 in the rat model of traumatic brain injury.
AB  - The acute inflammatory response plays an important role in secondary brain damage
      after traumatic brain injury (TBI). Neutrophils provide the main source of matrix
      metalloproteinases (MMPs) which also play a deleterious role in TBI. Numerous
      preclinical studies have suggested that hyperbaric oxygen therapy (HBOT) may by
      beneficial in various noncerebral and cerebral inflammatory diseases. The goal of
      this study was to evaluate the effects of HBOT on inflammatory infiltration and
      the expression of MMPs in correlation with secondary cell death in the rat model
      of dynamic cortical deformation (DCD). Twenty animals underwent DCD with
      subsequent HBOT (2.8 ATA, two sessions of 45 min each); 10 animals: DCD and
      normobaric oxygenation (1 ATA), 10 animals: not treated after DCD. Cell death was
      evaluated by TUNEL. Neutrophils were revealed by myeloperoxidase staining.
      Immunohistochemical staining for MMP-2 and -9 and tissue inhibitors of MMP-1
      (TIMP-1) and -2 was also performed and the results were quantitatively evaluated
      by image analysis. In the animals treated by HBOT, a significant decrease in the
      number of TUNEL-positive cells and neutrophilic inflammatory infiltration was
      seen in comparison with nontreated animals and those treated by normobaric
      oxygen. The expression of MMP-9 was also significantly lower in the treated
      group. Staining for MMP-2 and TIMP-2 did not change significantly. Our results
      demonstrate that HBOT decreased the extent of secondary cell death and reactive
      neuroinflammation in the TBI model. The decline of MMP-9 expression after HBOT
      may also contribute to protection of brain tissue in the perilesional area.
      Further research should be centred on the evaluation of long-term functional and
      morphological results of HBOT.

PMID- 16409553
TI  - Vascular colocalization of P-glycoprotein, multidrug-resistance associated
      protein 1, breast cancer resistance protein and major vault protein in human
      epileptogenic pathologies.
AB  - Multidrug transporters, such as P-glycoprotein (P-gp), multidrug-resistance
      associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), are
      associated with multidrug resistance in cancers; other molecules, such as major
      vault protein (MVP), have a similar association with drug-resistant cancer. These
      proteins are postulated to generate drug resistance in epilepsy. They have been
      shown individually to be up-regulated in epileptogenic brain tissue. In any
      consideration of the function, inhibition or evasion of the activity of such
      proteins, the colocalization of such proteins needs to be understood. We
      systematically determined the presence of such colocalization, focusing on
      microvascular endothelium from epileptogenic human brain tissue. Double labelling
      immunofluorescence and confocal laser scanning microscopy were used to determine
      colocalization of P-gp, MRP1, BCRP and MVP in one case of hippocampal sclerosis
      and two cases of focal cortical dysplasia type IIb. Endothelial colocalization
      was examined with double labelling using antibodies to CD34 and Factor VIII. The
      presence of P-gp, BCRP and MVP in microvascular endothelium was confirmed. P-gp,
      BCRP and MVP colocalized in microvascular endothelium, though not all proteins
      appeared to be identically distributed within this tissue. MRP1 did not
      colocalize to endothelium. These findings were not unexpected but required formal
      confirmation. The demonstrated colocalization of P-gp, BCRP and MVP in
      microvascular endothelium in epileptogenic human brain tissue has important
      implications for functional experiments (including single knock-out mice
      studies), work with specific and broad-spectrum inhibitors of transport function,
      and any eventual trials of treatment of refractory epilepsy involving modulation
      of the function of these proteins.

PMID- 16409554
TI  - Lipocalin-type prostaglandin D synthase (beta-trace) is upregulated in the alphaB
      crystallin-positive oligodendrocytes and astrocytes in the chronic multiple
      sclerosis.
AB  - Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly synthesized in
      leptomeningeal cells and oligodendrocytes (OLs) in rodents and humans, is
      secreted into the human cerebrospinal fluid (CSF) as beta-trace. L-PGDS protects
      OLs and neurones against apoptosis in twitcher mice, a murine model of Krabbe's
      disease, and is the second only to a stress protein, alphaB-crystallin, as the
      most abundant gene product upregulated in the demyelinating focus of multiple
      sclerosis (MS). Here we report that although the CSF level of L-PGDS is not
      increased in MS patients, L-PGDS is increased in the white matter of MS patients,
      especially in the shadow plaque as compared with the normal white matter. L-PGDS
      immunoreactivity was intensely expressed in OLs within the shadow plaques and in
      hypertrophied astrocytes within the chronic plaques of MS patients. Both L-PGDS
      positive OLs and astrocytes expressed a stress protein, alphaB-crystallin. These
      results suggest that the upregulation of L-PGDS occurs in OLs and astrocytes as a
      stress reaction.

PMID- 16409555
TI  - Age-related changes in striatal nitric oxide synthase-immunoreactive
      interneurones in the dystonic dtsz mutant hamster.
AB  - The dt(sz) mutant hamster represents a model of paroxysmal dyskinesia in which
      dystonic episodes can be age-dependently induced by stress. GABAergic
      interneurones which co-express calcium binding proteins were found to be reduced
      in the striatum of the dt(sz) mutant. Other types of striatal interneurones have
      so far not been examined. In the present study, we therefore determined the
      density of nitric oxide synthase (NOS)-immunoreactive interneurones in the
      striatum of the dt(sz) mutant in comparison with nondystonic control hamsters. At
      the age of most marked expression of dystonia (30-40 days of life), the density
      of NOS-positive interneurones was decreased in the striatum of dt(sz) hamsters (
      21%) in comparison with age-matched nondystonic control hamsters. Spontaneous
      remission of dystonia (age >90 days) coincided with a normalization of the
      density of NOS-reactive interneurones within the whole striatum of dt(sz)
      hamsters, but there remained a reduced density in distinct subregions. Together
      with previous findings the present data indicate that the development of striatal
      interneurones is retarded in mutant hamsters. The age-related deficit of NOS
      reactive interneurones may at least in part contribute to an abnormal activity of
      striatal GABAergic projection neurones and thereby to the age-dependent dystonic
      syndrome in the dt(sz) mutant.

PMID- 16409556
TI  - Ubiquitin-positive inclusions and progression of pathology in frontotemporal
      dementia and motor neurone disease identifies a group with mainly early
      pathology.
AB  - Frontotemporal lobar degeneration (FTLD) with tau-negative, ubiquitin-positive
      inclusions has been a topic of major interest in recent years, with this group
      now accounting for the majority of tau-negative cases of frontotemporal
      degeneration. The severity of neurodegeneration in FTLD is dependent on the stage
      of disease and is substantial even in the earliest stages. Elucidating the
      pathogenesis of FTLD requires evaluation of changes during the earliest possible
      stage of disease. However, the long survival of most frontotemporal dementia
      cases means that cases with early neuropathology are not frequently encountered.
      Cases of FTLD with the shortest survival are those with coexisting motor neurone
      disease (FTLD + MND), making these the ideal group for studying early FTLD
      pathology. It is not clear, however, what the pathological contribution of MND is
      in these cases. This study evaluates the pathology of 20 cases of FTLD (11 with
      no clinical signs of MND and nine with FTLD + MND) as well as 10 cases of MND
      without dementia. Our findings indicate that the deposition of ubiquitin does not
      play a key role in the neurodegenerative process in FTLD, and that the severity
      of neurodegeneration in FTLD is similar in cases with and without clinical MND.

PMID- 16409557
TI  - SUMOylation substrates in neuronal intranuclear inclusion disease.
AB  - Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative
      disorder characterized pathologically by the presence of ubiquitinated
      intranuclear inclusions (NII) in neuronal cells. We demonstrate that NIIs in both
      sporadic and familial NIID contained the small ubiquitin modifier-1 (SUMO-1) and
      the SUMOylation substrates promyelocytic leukaemia protein (PML) and histone
      deacetylase 4 (HDAC4). Both PML and SUMO-1 are major components of nuclear bodies
      (NBs), suggesting that the NIIs in NIID, as well as the intranuclear inclusions
      in polyglutamine diseases, might derive from these intranuclear functional
      domains that serve as sites for ubiquitin-related protein degradation. HDAC4 was
      also a major component of the NIIs. HDACs are transcriptional corepressors that
      regulate histone remodelling, and NBs are thought to be sites at which the level
      of histone acetylation is controlled. The presence of PML, SUMO-1 and HDAC4 in
      NIIs suggests that transcriptional activity regulated by histone acetylation
      might contribute to the disease process in NIID. In addition, we showed that
      another SUMOylation substrate, RanGAP1 is associated with NIIs only in the
      familial NIID patient. This might be explained by different pathogenetic
      mechanisms underlying subcategories of NIID, which is very heterogeneous.

PMID- 16409558
TI  - Continuous glucose monitoring and closed-loop systems.
AB  - BACKGROUND: The last two decades have witnessed unprecedented technological
      progress in the development of continuous glucose sensors, resulting in the first
      generation of commercial glucose monitors. This has fuelled the development of
      prototypes of a closed-loop system based on the combination of a continuous
      monitor, a control algorithm, and an insulin pump. METHOD: A review of
      electromechanical closed-loop approaches is presented. This is followed by a
      review of existing prototypes and associated glucose sensors. A literature review
      was undertaken from 1960 to 2004. RESULTS: Two main approaches exist. The
      extracorporeal s.c.-s.c. approach employs subcutaneous glucose monitoring and
      subcutaneous insulin delivery. The implantable i.v.-i.p. approach adopts
      intravenous sampling and intraperitoneal insulin delivery. Feasibility of both
      solutions has been demonstrated in small-scale laboratory studies using either
      the classical proportional-integral-derivative controller or a model predictive
      controller. Performance in the home setting has yet to be demonstrated.
      CONCLUSIONS: The glucose monitor remains the main limiting factor in the
      development of a commercially viable closed-loop system, as presently available
      monitors fail to demonstrate satisfactory characteristics in terms of reliability
      and/or accuracy. Regulatory issues are the second limiting factor. Closed-loop
      systems are likely to be used first by health-care professionals in controlled
      environments such as intensive care units.

PMID- 16409559
TI  - Will ASCOT change the form of anti-hypertensive therapy?

PMID- 16409560
TI  - Short-term effects of severe dietary carbohydrate-restriction advice in Type 2
      diabetes--a randomized controlled trial.
AB  - OBJECTIVE: This study sought to examine the effects of a 3-month programme of
      dietary advice to restrict carbohydrate intake compared with reduced-portion, low
      fat advice in obese subjects with poorly controlled Type 2 diabetes. RESEARCH
      DESIGN AND METHODS: One hundred and two patients with Type 2 diabetes were
      recruited across three centres and randomly allocated to receive group education
      and individual dietary advice. Weight, glycaemic control, lipids and blood
      pressure were assessed at baseline and 3 months. Dietary quality was assessed at
      the end of study. RESULTS: Weight loss was greater in the low-carbohydrate (LC)
      group (-3.55 +/- 0.63, mean +/- sem) vs. -0.92 +/- 0.40 kg, P = 0.001) and
      cholesterol : high-density lipoprotein (HDL) ratio improved (-0.48 +/- 0.11 vs. 
      0.10 +/- 0.10, P = 0.01). However, relative saturated fat intake was greater
      (13.9 +/- 0.71 vs. 11.0 +/- 0.47% of dietary intake, P < 0.001), although
      absolute intakes were moderate. CONCLUSIONS: Carbohydrate restriction was an
      effective method of achieving short-term weight loss compared with standard
      advice, but this was at the expense of an increase in relative saturated fat
      intake.

PMID- 16409561
TI  - A predictive tool for the self-management of diabetes (Librae): evaluation using
      a continuous glucose monitoring system.
AB  - AIMS: Diabetes self-management involves a difficult balancing act between
      insulin, food and exercise. The challenge is to develop innovative, validated
      algorithms to aid patient decision-making and optimize glycaemic control.
      'Librae' is a computerized diabetes simulator in diary format, developed as an
      educational predictive tool for patients, reducing 'trial and error' by allowing
      patients to simulate and experiment with dietary or insulin adjustments on a
      'body double'. We have evaluated the predictive ability of Librae using
      continuous blood glucose monitoring (CGMS). METHODS: Patients with Type 1
      Diabetes attending the Paediatric Clinic were invited to use 'Librae' for 1 week
      and were then fitted with a CGMS for 72 h. The predictive ability of 'Librae' was
      compared with concurrent data obtained from the CGMS. RESULTS: Seven thousand
      nine hundred and sixty paired blood glucose values were obtained from the 11
      patients who completed the study. 'Librae' underestimated the measured CGMS
      values, the error having a positive mean of 0.35 mmol/l (95% confidence interval
      0.22-0.48 mmol/l). However, Librae tended to overestimate at low levels of blood
      glucose readings, and underestimate at high levels of blood glucose readings.
      CONCLUSION: The modelled values of 'Librae' correlated well with the CGMS data,
      but clinically unacceptable errors occurred at extremes of blood glucose levels.
      Concurrent CGMS recordings have provided a large data set to modify and improve
      the existing Librae model and patient feedback has led to improvements in its
      usability. Librae may provide a useful tool to improve diabetes self-management
      education and optimize glycaemic control.

PMID- 16409562
TI  - Attentional functioning is impaired during acute hypoglycaemia in people with
      Type 1 diabetes.
AB  - AIMS: To examine the effects of acute insulin-induced hypoglycaemia on different
      aspects of attention and on general non-verbal reasoning in people with Type 1
      diabetes. METHODS: A hyperinsulinaemic glucose clamp was used to maintain
      euglycaemia (4.5 mmol/l) or induce hypoglycaemia (2.6 mmol/l) on separate
      occasions in 16 adults with Type 1 diabetes each of whom were studied on two
      occasions in a counterbalanced order. During each study condition, the subjects
      completed parallel tests of cognitive function assessed by the Test of Everyday
      Attention and the Raven's Progressive Matrices. RESULTS: Hypoglycaemia caused a
      significant deterioration in tests sensitive to visual and auditory selective
      attention. During hypoglycaemia, attentional flexibility deteriorated and speed
      of information processing was delayed. Sustained attention and intelligence
      scores were preserved during hypoglycaemia. CONCLUSIONS: In people with Type 1
      diabetes, hypoglycaemia causes a significant deterioration in attentional
      abilities, while non-verbal reasoning is preserved. It is likely therefore that
      many complex cognitive tasks which involve attention will be impaired during
      moderate hypoglycaemia during everyday life.

PMID- 16409563
TI  - Hippocampal volume and cognitive performance in long-standing Type 1 diabetic
      patients without macrovascular complications.
AB  - AIMS: Hippocampal atrophy and memory deficits have been reported in Type 2
      diabetes. Whether similar alterations occur in Type 1 diabetes is currently
      unknown. METHODS: In a case-control design, 13 Type 1 diabetic patients with at
      least 10 years' duration of disease, but free from clinical signs of
      macrovascular disease, were compared with age- and gender-matched control
      subjects. Hippocampal volume and measures of global cerebral cerebrospinal fluid
      (CSF) were determined from magnetic resonance imaging (MRI) scans. Cognitive
      functions were assessed using four neuropsychological tests. Mood and depression
      were measured by questionnaires. RESULTS: Hippocampal volume and memory did not
      differ between Type 1 diabetic patients and control subjects. However, a
      significantly increased amount of cerebral CSF suggestive of mild cerebral
      atrophy was observed in the patients. In addition, deficits in psychomotor speed
      and selective attention were apparent. Eleven of 13 patients had retinopathy
      and/or nephropathy. Findings were unrelated to cerebrovascular disease, white
      matter disease or silent strokes. CONCLUSIONS: Results from our small study in
      Type 1 diabetic patients do not support findings from previous studies of Type 2
      diabetic patients demonstrating reductions in hippocampal volume and impaired
      memory. On the contrary, we observed evidence for mild cerebral atrophy and
      impaired psychomotor speed and selective attention. This is in line with some
      previous studies in Type 1 diabetes. If replicated in larger studies, our
      findings would support the idea that the effects on brain function and structure
      differ between Type 1 and Type 2 diabetes.

PMID- 16409564
TI  - Effect of a pocket-size tablet-dispensing device on glycaemic control in Type 2
      diabetic patients.
AB  - AIM: To evaluate whether a pocket-size tablet-dispensing device would improve
      adherence to therapy as judged by reduction of HbA(1c) levels in a large
      population of Type 2 diabetic patients. METHODS: The study design was
      prospective, randomized, open label with two parallel groups. Patients (2296)
      were recruited from general practitioners and internists and randomized to either
      receive a tablet dispenser (TD) or no intervention (control group, CO). Patients'
      characteristics and current oral therapy (including dosage) were recorded at
      baseline. HbA(1c) was compared between groups at baseline and after 6 months'
      intervention. RESULTS: Data were available in 2081 patients. Baseline
      characterisitcs, including age, body mass index (BMI), blood pressure and gender
      distribution were comparable between the two groups, as was HbA(1c)[7.9 (7.9
      8.0), TD vs. 8.0 (7.9-8.0)%, CO, means (95% CI)]. After 6 months, HbA(1c)
      improved in both groups, but improvement was significantly greater in TD than in
      controls [-0.74 (0.67-0.80) vs. -0.53 (0.47-0.59)%, P < 0.0001]. Possession of a
      dispenser remained an independent predictor of improved control in a multiple
      regression model. In the subgroup analysis, the effect was significantly more
      pronounced (i) in patients receiving more medications and (ii) more diabetes
      medications per day (iii) in younger patients. CONCLUSION: In this large study
      population in a 'realistic' setting, a simple tablet-dispensing device led to a
      significant and clinically relevant improvement in HbA(1c) levels. Because
      patients with a more complex therapy regimen benefited more, we suggest that TD
      might have improved adherence to therapy.

PMID- 16409565
TI  - Optimal timing of injection of once-daily insulin glargine in people with Type 1
      diabetes using insulin lispro at meal-times.
AB  - AIMS: To compare blood glucose control when insulin glargine is given at lunch
      time, dinner-time, and bed-time in people with Type 1 diabetes using insulin
      lispro at meal-times. METHODS: In this 16-week, three-way, cross-over study, 23
      people with Type 1 diabetes were randomized to insulin glargine injection at
      lunch-time (L) [mean 12.37 +/- 00.34 (+/- sd) h], dinner-time (D) (18.12 +/-
      00.40 h), or bed-time (B) (22.29 +/- 00.40 h), each plus meal-time insulin
      lispro. Each 4-week treatment period concluded with a 24-h inpatient metabolic
      profile. RESULTS: Insulin doses, HbA(1c), and fructosamine concentration did not
      differ between treatment periods. Pre-breakfast self-monitored blood glucose
      (SMBG) concentration was higher with injection of glargine at lunch-time than at
      other times [L: 9.2 +/- 0.3 (+/- se) vs. D: 8.2 +/- 0.3 or B: 8.0 +/- 0.3 mmol/l,
      P = 0.016], as probably was pre-lunch SMBG (L: 8.6 +/- 0.7 vs. D: 6.4 +/- 0.7 or
      B: 6.4 +/- 0.8 mmol/l, P = 0.051). Pre-dinner SMBG level was higher with dinner
      time glargine than other injection times (D: 9.4 +/- 0.9 vs. L: 4.9 +/- 0.9 or B:
      7.4 +/- 1.1 mmol/l, P = 0.007). For 22.00 to 02.00 h, mean inpatient plasma
      glucose concentration was higher with injection of glargine at bed-time than
      other times (B: 9.1 +/- 0.6 vs. L: 7.8 +/- 0.6 or D: 6.7 +/- 0.6 mmol/l, P =
      0.023). Plasma free insulin concentration was lower at the end of the afternoon
      with dinner-time glargine than other injection times (D: 11.5 +/- 1.4 vs. L: 20.2
      +/- 1.3 or B: 16.5 +/- 1.3 mU/l, P < 0.001). Frequency of hypoglycaemia was not
      different, but timing of hypoglycaemia differed between treatment periods.
      CONCLUSIONS: Blood glucose levels rise around the time of injection of insulin
      glargine whether given at lunch-time, dinner-time or bed-time. Bed-time injection
      leads to hyperglycaemia in the early part of the night which is improved by
      giving insulin glargine at lunch-time or dinner-time.

PMID- 16409566
TI  - Angiotensin II does not affect endothelial tone in Type 1 diabetes-results of a
      double-blind placebo controlled trial.
AB  - AIMS: Previously, we have demonstrated that patients with normoalbuminuric Type 1
      diabetes are characterized by impaired nitric oxide bioavailability compensated
      for by increased vasodilatory prostanoid-mediated vasodilation. Experimental
      evidence suggests vascular responses to endogenous angiotensin II involve the
      nitric oxide and prostaglandin pathways. We examined whether selective blockade
      of angiotensin II influences endothelial tone with particular reference to the
      nitric oxide/prostaglandin pathways in patients with Type 1 diabetes free from
      vascular complications. METHODS: At baseline, we studied changes in forearm blood
      flow in response to brachial arterial infusions of acetylcholine, l-NMMA, a
      combination of l-NMMA and the cyclo-oxygenase inhibitor indomethacin and
      nitroprusside in 30 patients with normoalbuminuric Type 1 diabetes [21 male, 9
      female; age 38.5 +/- 1.9 years (mean +/- sem)]. Patients were randomized to 2
      weeks' treatment with placebo or the selective angiotensin II receptor blocking
      agent irbesartan, 300 mg, prior to forearm vasoactive responses being re
      examined. RESULTS: The forearm responses to nitroprusside and acetylcholine were
      unchanged by both placebo (P = 0.23 and P = 0.36, respectively) and irbesartan (P
      = 0.41 and P = 0.36). Similarily, dose-response curves to acetylcholine in the
      presense of l-NMMA alone (P = 0.42) and a combination of l-NMMA and indomethacin
      (P = 0.44) were not altered by angiotensin II blockade. CONCLUSION: This study
      demonstrated that physiological blockade of endogenous angiotensin II in Type 1
      diabetes does not augment agonist-evoked vasodilation or the contribution of
      nitric oxides and prostanoids to endothelial tone.

PMID- 16409567
TI  - Reported symptoms and quality-of-life impacts in patients having laser treatment
      for sight-threatening diabetic retinopathy.
AB  - AIMS: To explore the patient experience of symptoms of eye disease related to
      diabetes and its treatment, including increase of symptoms over time and their
      relation to severity of the condition and the effect of multiple treatments and
      symptoms on quality of life. METHODS: A qualitative interview study was
      implemented at four eye clinics in the UK. This study design was intended to
      yield 240 interviews in patients having their first laser treatment or first
      follow-up and in multi-treatment patients with a clinically documented loss of
      visual function in at least one eye (VA </= 6/12). The intention was to have an
      approximately equal number of patients with proliferative diabetic retinopathy
      (PDR) or macular oedema (MO). RESULTS: A total of 227 interviews were completed
      (54% PDR and 46% MO). The most frequently reported symptom prior to initial
      treatment was blurred vision (55%). First-time-treatment patients reported fewer
      symptoms than the multi-treatment patients. After a pronounced reduction of
      quality-of-life impacts after the first laser treatment, results all demonstrate
      an increasing impact as patients move from first treatment to multiple
      treatments. The main responses regarding satisfaction with laser treatment were
      that, although patient expectations were basically met, the treatment had less of
      an impact than they hoped for, and they would have the treatment again if needed.
      CONCLUSIONS: The current study provides a qualitative exploration of visual
      symptoms, levels of self-reported visual impairment, and general description of
      the areas of impact or restriction that patients experienced due to their eye
      disease, both pre- and post-laser treatment.

PMID- 16409568
TI  - Islet autoimmunity and genetic mutations in Chinese subjects initially thought to
      have Type 1B diabetes.
AB  - AIMS: To explore the contribution of islet autoimmunity and genetic mutations in
      Chinese patients initially thought to have Type 1B diabetes. METHODS: A group of
      33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the
      absence of autoantibodies to glutamic acid decarboxylase (GAD), IA-2, insulin,
      thyroid globulin or thyroid peroxidase, or high-risk HLA-DQ haplotypes. The
      cohort was further characterized by measurement of autoantibodies to
      carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for
      genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes.
      Mutations of HNF-1alpha (MODY3) and neuroD1/beta2 (MODY6) genes were screened
      using the single-strand conformation polymorphism (SSCP) technique and
      sequencing. Mitochondrial DNA mutations were analysed with polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Within the
      cohort, we found one patient with a novel mutation, R321H (CGC-->CAC) in exon 5
      of the HNF-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA,
      five with Ala45Thr polymorphisms in the neuroD1/beta2 gene, and two patients with
      autoantibodies to SOX13. CONCLUSIONS: Some of the Chinese patients originally
      thought to have Type 1B diabetes do have other evidence of islet autoimmunity and
      genetic mutations involved in the underlying aetiology. This suggests that more
      rigorous screening for these conditions is needed before classifying subjects as
      having Type 1B diabetes.

PMID- 16409569
TI  - Common promoter polymorphism in monocyte differentiation antigen CD14 is
      associated with serum triglyceride levels and body mass index in non-diabetic
      individuals.
AB  - AIMS: Growing evidence supports the hypothesis that chronic low-grade
      inflammation related to innate immunity may play an important role in the
      pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation
      antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and
      augments monocyte/macrophage inflammatory responses. METHODS: We have sequenced
      the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5'
      flanking region. Two common loci (minor allele frequency > 0.05) were genotyped
      in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.
      RESULTS: Eight polymorphisms, including four non-synonymous forms, were
      identified in CD14. No polymorphisms were found in association with T2DM.
      However, one common promoter SNP (-260T>C) was significantly associated with both
      the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic
      control subjects. Individuals who carried the minor allele (C) had higher TG
      levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/-
      3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T
      genotypes. CONCLUSION: Our data suggest that lipid metabolism and obesity,
      important pathophysiological elements of T2DM and the metabolic syndrome, are
      regulated by complex mechanisms that include the CD14 gene polymorphism-mediated
      genetic propensity to non-specific inflammatory responses.

PMID- 16409570
TI  - Cross-sectional correlates of fasting hyperinsulinaemia in post-menopausal women
      of different ethnic origin.
AB  - AIMS: In a large ethnically diverse nationwide sample of post-menopausal women we
      explored the relationship between fasting insulin levels, ethnicity, and a wide
      range of anthropometric, socio-economic, and lifestyle factors. METHODS: Subjects
      were post-menopausal women aged 50-79 years without diagnosed diabetes mellitus
      comprising a subsample (n = 3500) of the Women's Health Initiative (WHI) Clinical
      Trial and Observational Study. In a cross-sectional survey at baseline, we
      analysed the association between ethnicity and fasting insulin using analysis of
      covariance procedures and identified independent correlates of hyperinsulinaemia,
      defined by the 75th percentile cut point for each ethnic group. RESULTS: Fasting
      insulin levels were higher among African-American and Hispanic women than among
      non-Hispanic White or Asian women. These differences persisted after adjustment
      for age, educational attainment, total and central body obesity, adult weight
      change, family history of diabetes, smoking status, alcohol consumption, use of
      menopausal hormone therapy and physical activity. Higher levels of body mass
      index, waist-hip ratio, adult weight gain, and lower levels of total and moderate
      or strenuous recreational activity were independent correlates of fasting
      hyperinsulinaemia. Habitual walking was also inversely associated with fasting
      insulin. CONCLUSIONS: In this cross-sectional analysis, fasting insulin levels
      were higher among African-American and Hispanic post-menopausal women as compared
      with non-Hispanic White and Asian women. In addition, obesity, adult weight gain,
      and low levels of moderate or strenuous physical activity were independently
      associated with hyperinsulinaemia.

PMID- 16409571
TI  - Insulin pump therapy in childhood diabetes-cost implications for Primary Care
      Trusts.
AB  - AIMS: Primary Care Trusts (PCTs) are now responsible for the planning and
      delivery of health-care services throughout England and Wales. As the 25 PCTs
      throughout Yorkshire are representative of the national distribution in terms of
      population structure and socio-economic status, we aimed to address the paucity
      of information describing the burden of childhood diabetes in primary care and to
      evaluate the cost implications of insulin pump therapy on individual PCTs.
      METHODS: We extracted information from a population-based register in Yorkshire,
      including 1952 patients diagnosed under the age of 15 years from 1990 to 2003.
      Each patient's postcode was linked to an individual PCT. Incidence rates (per 100
      000 patient years) were derived and assessed for evidence of heterogeneity across
      PCTs and within Strategic Health Authorities (SHAs). RESULTS: Incidence rates
      were lower in West Yorkshire (19.1, 95% CI 18.0-20.2) than North-east Yorkshire
      (20.3, 18.9-21.6), although this difference was not significant (P = 0.20). No
      significant evidence of heterogeneity in incidence rates was observed across PCTs
      (P = 0.46). Ninety per cent of all PCTs would expect four to seven newly
      diagnosed children per year, corresponding to a single general practitioner (GP)
      referring an individual for diagnosis once every 15 years on average. Assuming 1%
      of current patients under the age of 15 years with diabetes were to move onto
      insulin pump therapy, this would impose an additional cost of pound400-1300 per
      year for each PCT. The average cost was 15% lower for PCTs in West Yorkshire than
      North and East Yorkshire. CONCLUSIONS: The additional resources required to pay
      for insulin pump therapy for a small proportion of the diabetes population would
      be minimal given the potential benefits to these patients of improved control and
      anticipated reduction in long-term morbidity.

PMID- 16409572
TI  - On-line adaptive algorithm with glucose prediction capacity for subcutaneous
      closed loop control of glucose: evaluation under fasting conditions in patients
      with Type 1 diabetes.
AB  - AIMS: To evaluate an algorithm with glucose prediction capacity and continuous
      adaptation of patient parameters-a model predictive control (MPC) algorithm-to
      control blood glucose concentration during fasting conditions in patients with
      Type 1 diabetes. In the subcutaneous (sc) route within a closed loop system.
      METHODS: Paired experiments were performed in six patients. Over 8 h the MPC
      algorithm was used to control glucose with s.c. insulin administration and two
      different glucose monitoring protocols: first, the algorithm was provided with
      intravenous (i.v.) glucose values for insulin dosage calculation directly (i.v.
      s.c. route). Then, in the second experiment, i.v. glucose values were fed to the
      MPC with a delay of 30 min to simulate s.c. glucose measurements ('s.c.'-s.c.
      route). In both experiments plasma glucose, insulin dosage, and serum insulin
      levels were analysed. RESULTS: Glucose concentration was brought from hyper- to
      normoglycaemia and kept in the physiological range (6-7 mmol/l) with both routes
      in all subjects. Mean glucose concentration reached the threshold of 7 mmol/l
      approximately 2 (i.v.-s.c. route) and 3 ('s.c.'-s.c. route) hours after the start
      of glucose control with the MPC. During the last 2 h of automated glucose
      control, mean glucose concentration was 6.3 +/- 0.2 mmol/l and 6.6 +/- 0.3 mmol/l
      for i.v.-s.c. and 's.c.'-s.c. route, respectively. Glucose concentration, insulin
      doses, and serum insulin levels did not differ significantly between routes (P >
      0.05). CONCLUSIONS: The MPC algorithm is suitable for glucose control during
      fasting within an extracorporeal artificial beta-cell in the subcutaneous route
      Type 1 diabetic patients.

PMID- 16409573
TI  - A comparison of glycaemic and metabolic control over time among South Asian and
      European patients with Type 2 diabetes: results from follow-up in a routine
      diabetes clinic.
AB  - AIMS: Although South Asians have a higher prevalence of diabetes which develops
      at a younger age, data on change in metabolic parameters post-diagnosis are
      relatively sparse. We therefore wished to determine whether South Asians with
      diabetes had similar or greater year-on-year deterioration in metabolic
      parameters compared with Europeans. METHODS: We analysed longitudinal change in
      metabolic parameters [glycated haemoglobin (HbA(1c)), blood pressure, body mass
      index (BMI), lipids] among South Asian (n = 210) and European (n = 1557) patients
      consecutively attending the same diabetes clinic over a mean period of 5.3 years.
      RESULTS: South Asians were younger than Europeans at first recorded diagnosis of
      diabetes (mean age 45.9 vs. 57.3 years, P < 0.001) and had significantly lower (
      approximately 1.2 units) BMI and blood pressure. Mean HbA(1c) was not different
      across ethnic groups at first visit, but with time glycaemic control was worse in
      South Asians than Europeans, with average deterioration 1.31% (= 0.23%/year) in
      Asians vs. 0.82% (0.16%/year) in Europeans, P = 0.003. This ethnic difference in
      mean change in HbA(1c) persisted after adjustment for age, sex, baseline HbA(1c),
      and weight change in linear regression analysis (beta = 0.46, 95% CI 0.24-0.69, P
      < 0.001), and with additional adjustment for time to referral and duration of
      diabetes (P = 0.01). Moreover, South Asians had significantly smaller
      improvements in blood pressure (P < 0.001) and cholesterol (P = 0.044) over the
      follow-up period in keeping with fewer prescriptions of anti-hypertensive agents
      and lipid-lowering agents. CONCLUSIONS: These data suggest the need to be more
      aggressive in the management of diabetes and related risk factors in South
      Asians.

PMID- 16409574
TI  - Comparison of microbiological results of needle puncture vs. superficial swab in
      infected diabetic foot ulcer with osteomyelitis.
AB  - AIM: To study prospectively two methods for the bacteriological diagnosis of
      osteomyelitis related to diabetic foot ulcer: needle puncture performed across
      normal skin surrounding the foot ulcer and superficial swabbing of the ulcer.
      PATIENTS AND METHODS: Diabetic patients with a foot ulcer complicated by bone or
      joint infection, as detected by X-ray imaging, were included in the study. Ulcer
      swabbing and needle puncture were performed in each patient. To reach the tissue
      nearest the bone surface, needle puncture was guided by X-ray imaging and the
      drop of fluid obtained by aspiration was used for both aerobic and anaerobic
      bacterial culture. RESULTS: Twenty-one diabetic patients were included. The mean
      number of microorganisms isolated by needle puncture was significantly lower
      compared with that obtained by superficial swabbing: 1.09 vs. 2.04 (P < 0.02).
      Three bacterial species were isolated by needle puncture only in one patient
      while three or more bacterial isolates were obtained by superficial swabbing in
      six patients. No bacterial isolate was detected in five patients by needle
      puncture and in two patients by superficial swabbing. Staphylococcus aureus
      accounted for 70% of cases (seven patients) when a single bacterial species was
      obtained by needle puncture. After needle puncture, no wound complication or
      infection was observed. CONCLUSION: Culture of samples obtained by needle
      puncture revealed one or two bacterial isolates in two-thirds of diabetic
      patients with osteomyelitis following foot ulcer. Given the lack of
      complications, this invasive diagnostic technique should be considered for deep
      direct sampling in diabetic patients with osteomyelitis related to foot ulcer
      when surgical debridement is contraindicated or delayed.

PMID- 16409575
TI  - The impact of HIV/AIDS on Type 2 diabetes prevalence and diabetes healthcare
      needs in South Africa: projections for 2010.

PMID- 16409576
TI  - A case of insulin autoimmune syndrome with HLA DRB1*0404: impact on the
      hypothesis for the molecular pathogenesis involving DRB1 molecules.

PMID- 16409577
TI  - Liver failure in a patient receiving rosiglitazone therapy.

PMID- 16409580
TI  - Reduced mortality rate associated with annual mammograms after breast cancer
      therapy.
AB  - Guidelines have been developed for appropriate posttherapy surveillance for
      breast cancer recurrence. One purpose of posttherapy surveillance is to detect
      potentially curable local recurrences and new cancers in the opposite breast. The
      objective of this investigation was to assess the impact of annual mammography on
      all-cause mortality in breast cancer survivors. We conducted a case-control
      analysis nested in a cohort of 865 stage I or II breast cancer patients diagnosed
      from 1996 to 1999. The exposure variable was the number of mammograms received
      after completing primary therapy. Cases were decedents and we used risk-set
      sampling to match eight controls to each case on follow-up time. The mortality
      rate declined with an increasing number of mammograms (p for trend=0.007). The
      age- and therapy-adjusted odds ratio associating receipt of an additional
      mammogram, compared with receipt of no mammogram, equaled 0.77 (95% confidence
      interval [CI] 0.53-1.1). These results are consistent with a protective effect of
      regular surveillance mammography after completing therapy for early stage breast
      cancer.

PMID- 16409581
TI  - Disengagement and social support moderate distress among women with a family
      history of breast cancer.
AB  - Using a cross-sectional, exploratory design, this pilot study analyzed the
      relationships between familial history of breast cancer and psychological
      distress in order to evaluate who is more distressed and to assess the possible
      need for intervention. Coping style, social support, and family relations were
      investigated as potential moderators of these relationships. Participants were 45
      women with a familial history of breast cancer recruited from the Family Registry
      for Breast Cancer (FRBC) at the Northern California Cancer Center (NCCC).
      Contrary to previous reports of similar cohorts, the overall level of
      psychological distress in this cohort was comparable to normative samples. The
      number of relatives with breast cancer was related to distress as measured by the
      State-Trait Anxiety Inventory (STAI) scale, but there was no significant
      differentiation in distress associated with the number of first-degree as
      compared to second- and third-degree relatives with breast cancer. Having more
      relatives that had died from breast cancer was associated with greater distress
      on a number of measures. The number of first-degree relative deaths, including
      maternal death, was also associated with distress. Positive and network support,
      disengagement coping responses, and family cohesion were each significant
      moderators of the impact of family history on distress. This association between
      distress and disengagement is similar to that found in metastatic breast cancer
      patients themselves, and the findings suggest a subgroup that merits and might
      respond to more intensive intervention to provide support and facilitate
      emotional expression.

PMID- 16409582
TI  - Computer-aided detection in full-field digital mammography: detection in
      dependence of the BI-RADS categories.
AB  - The object of this study was to determine the performance of a computer-aided
      detection system in full-field digital mammography (Senographe 2000D, General
      Electric, Buc, France) in detecting carcinomas in breasts in dependence of the
      initial Breast Imaging Reporting and Data System (BI-RADS) categories. A total of
      226 mediolateral oblique (MLO) and 186 craniocaudal (CC) view mammograms of
      histologically proven cancers were retrospectively evaluated with a primary
      digital computer-aided detection system (Image Checker V2.3; R2 Technology, Los
      Altos, CA). According to BI-RADS of the American College of Radiology (ACR), the
      lesions were classified in MLO view as BI-RADS 1 in 2 cases, BI-RADS 2 in 11
      cases, BI-RADS 3 in 37 cases, BI-RADS 4 in 56 cases, and BI-RADS 5 in 120 cases,
      and in CC view as BI-RADS 1 in 2 cases, BI-RADS 2 in 8 cases, BI-RADS 3 in 26
      cases, BI-RADS 4 in 46 cases, and BI-RADS 5 in 104 cases. The computer-aided
      detection system shows markers also in mammograms classified as BI-RADS
      categories 1-3 by the radiologist. Furthermore, BI-RADS categories 4 and 5 in
      most cases demonstrate masses in mammography. With increasing BI-RADS category,
      the computer-aided detection system shows decreasing numbers of overlooked
      carcinomas. In MLO view, no markers were found in 100% (2/2), 81.8% (9/11), 59.5%
      (22/37), 46.4% (26/56), and 15% (18/120) for BI-RADS categories 1-5,
      respectively. False-positive markers, however, were seen in 0.5 per image
      (205/412). In conclusion, the high rate of false-positive markers shows that the
      specificity of the computer-aided detection system is limited and that
      improvements are necessary.

PMID- 16409583
TI  - Ductal carcinoma in situ: trends in geographic, temporal, and demographic
      patterns of care and survival.
AB  - While long-term prognosis is excellent, treatment of ductal carcinoma in situ
      (DCIS) remains controversial and inconsistent. The purpose of this study was to
      track geographic and temporal patterns of care for women diagnosed with DCIS, and
      analyze subsequent cancer-specific risk of mortality. Subjects for this study
      were 41,245 women diagnosed with primary DCIS in the National Surveillance,
      Epidemiology, and End Results (SEER) program from 1973 through 2000. Variables
      analyzed included patient age, year of diagnosis, SEER site of residence at the
      time of diagnosis, treatment (surgery, radiation), race, age, and hormone
      (estrogen and progesterone) receptor status. The percentage of women diagnosed
      with DCIS out of the total number of women diagnosed with breast cancer increased
      steadily between 1973 and 2000, with the largest increase occurring around 1985.
      Breast conserving surgery (BCS) utilization increased over time for each SEER
      site to the current proportions, ranging from 49.5% in Utah to 76.9% in
      Connecticut. Younger women were significantly more likely to receive mastectomy
      and had significantly lower risk of death. Women receiving BCS who also had
      radiation therapy (RT) had a significantly lower risk of death, although those
      receiving mastectomy had the lowest risk of death. Black women and Asian/Pacific
      island women were significantly more likely to receive BCS, although black women
      were less likely to receive follow-up RT and had a significantly increased risk
      of death. Racial and age differences in the treatment of DCIS resulted in
      significantly disparate rates of survival, which should be considered in public
      health programming. Mastectomy utilization resulted in improved survival,
      although additional studies may elucidate the interaction of treatment with
      patient age.

PMID- 16409584
TI  - Breast conservation surgery achieving>or=2 mm tumor-free margins results in
      decreased local-regional recurrence rates.
AB  - Whether cosmetically acceptable tumor-free (>/=2 mm) surgical margins reduce the
      local-regional recurrence risk for patients treated with fractionated radiation
      therapy, chemotherapy, and hormonal therapy is unknown. The benefit of a minimum
      cosmetically acceptable tumor-free margin remains speculative because no
      contemporary studies have investigated the extent of invasive disease
      infiltration within the breast beyond the primary tumor. To address these
      clinical issues, we conducted a retrospective study of 341 women diagnosed with
      stage I or II invasive breast cancer to determine the rate of local in-breast,
      elsewhere in-breast, and ipsilateral regional lymph node recurrences of breast
      cancer after conservation surgery achieving either tumor-free (>or=2 mm) or close
      (>0 mm to <2 mm) surgical margins followed by whole breast radiation therapy over
      a 6-year period from January 1996 to December 2002. Women may have received
      adjuvant chemotherapy or hormonal therapy as clinically indicated. After a median
      follow-up of 56 months from the completion of breast conservation surgery, 14 of
      the 341 women (4.1%) developed breast cancer recurrences. Crude ipsilateral
      recurrence rates were 1.8% (4 of 222) for tumor-free (>or=2 mm) versus 8.4% (10
      of 119) for close (>0 mm to <2 mm) surgical margins (p=0.007). The estimated 5
      year cumulative local recurrence rate was significantly less for women with tumor
      free margins (2.1%) as compared to close surgical margins (8.9%) (p=0.004).
      Multivariate analyses identified negative estrogen receptor expression (p=0.004),
      close surgical margins (p=0.012), and the presence of angiolymphatic invasion
      (p=0.040) as prognostic factors for local-regional recurrences. Microscopically
      the extent of invasive disease infiltration beyond the primary tumor was on
      average 1 mm, with all measured invasive disease less than 1 cm. Based on our
      findings, cosmetically acceptable tumor-free (>or=2 mm) surgical margins
      significantly reduce local in-breast and regional lymph node recurrences with
      fractionated radiation therapy, chemotherapy, and hormonal therapy.

PMID- 16409585
TI  - Ascertaining prognosis for breast cancer in node-negative patients with
      innovative survival analysis.
AB  - Clinical decisions to administer adjuvant systemic therapy to women with early
      breast cancer require knowledge about baseline prognosis, which is only
      assessable in the absence of such adjuvant treatment, which most patients
      currently do receive. The Cox model is the standard tool for assessing the effect
      of prognostic factors; however, there may be substantive differences in the
      estimated prognosis obtained by the Cox model rather than a log-normal model. For
      more than 50 years, clinical breast cancer data for cohorts of patients have
      supported the choice of a log-normal model. The prognostic impact of model type
      is examined here for a cohort of breast cancer patients, only 7% of whom received
      adjuvant systemic therapy. We quantitated prognosis utilizing Kaplan-Meier, Cox,
      and log-normal survival analyses for 415 consecutive T1-T3, M0, histologically
      node-negative patients who were operated on for primary breast cancer at Women's
      College Hospital between 1977 and 1986. Recurrence outside the breast for disease
      free interval (DFI) and breast cancer death for disease-specific survival (DSS)
      were the events of interest. The patient follow-up for these investigations was
      96% complete: a median 8 years for those surviving. Factors used in these
      investigations were age, weight, tumor size, histology, tumor grade, nuclear
      grade, lymphovascular invasion, estrogen receptor (ER), progesterone receptor
      (PR), combined ER/PR receptor, overexpression of neu oncoprotein, DNA ploidy, S
      phase, and adjuvant therapy. In our study we found evidence against the Cox
      assumption of proportional hazards, which is not an assumption for the log-normal
      approach. We identified patients with greater than 96% and others with less than
      40% DSS at 10 years. The difference in prognosis determined by using the Cox
      versus the log-normal model ranged for DFI from 1.2% to 8.1%, and for DSS from
      0.4% to 6.2%; interestingly, the difference was more substantial for patients
      with a high risk of recurrence or death from breast cancer. Estimated prognoses
      may differ substantially by survival analysis model type, by amounts that might
      affect patient management, and we think that the log-normal model has a major
      advantage over the Cox model for survival analysis.

PMID- 16409586
TI  - The relationship of radiation pneumonitis to treated lung volume in breast
      conservation therapy.
AB  - Breast conservation therapy has become a common modality for therapy of early
      stage breast cancer. Most studies of primary lung irradiation correlate the risk
      of pneumonitis with the volume of lung treated. It is proposed that the lung
      volume treated during tangential radiation of the intact breast may be calculated
      from a measurement of the central lung distance. Central lung distance is the
      distance from the chest wall to the edge of the field at the central axis. This
      study examines whether the incidence of radiation pneumonitis indeed correlates
      with the lung volume treated as calculated from a measurement of the central lung
      distance. From January 1, 1985, through December 31, 1998, 353 patients were
      treated with breast conservation therapy at the University of Louisville. The
      charts were reviewed for any evidence of clinically significant radiation
      pneumonitis. The treatment films were obtained and the central lung distance
      ascertained. Four cases of radiation pneumonitis were identified. Three of these
      occurred after tangential radiation and one occurred in a retreatment field after
      bone marrow transplant. The overall rate of radiation pneumonitis was 1.2%. A
      central lung distance of less than 3 cm was found in 78.3% of patients and 21.7%
      had a central lung distance of three or greater. There was no correlation between
      central lung distance and the risk of radiation pneumonitis. Breast conservation
      therapy is a well-tolerated modality for treatment of early stage breast cancer.
      The incidence of radiation pneumonitis is very low and is usually associated with
      other factors in addition to the tangential field lung volume.

PMID- 16409587
TI  - Does the method of biopsy affect the incidence of sentinel lymph node metastases?
AB  - More detailed examination of the sentinel lymph node (SLN) in breast cancer has
      raised concerns about the clinical significance of micrometastases, specifically
      isolated tumor cells detected only through immunohistochemical (IHC) staining. It
      has been suggested that these cells do not carry the same biologic implications
      as true metastatic foci and may represent artifact. A retrospective institutional
      review board-approved review was conducted on clinically node-negative breast
      cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003.
      Retrospective analysis of tumor characteristics and the method of the initial
      diagnostic biopsy were correlated with the presence and nature of metastatic
      disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E)
      positive. SLN positivity strongly correlated with tumor size (p<0.001) and tumor
      grade (p=0.025), but not with the method of biopsy (needle versus excisional
      biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC
      (n=381). Of the 291 H&E-negative patients, 26 had IHC-only detected
      micrometastases (9%). The likelihood of detecting IHC-only metastases did not
      correlate with tumor size or grade, but was significantly higher in patients
      undergoing excisional biopsy than core needle biopsy. While the method of biopsy
      has no demonstrable effect on the likelihood of finding metastases in the SLN by
      routine serial sectioning and H&E staining, it may significantly impact the
      likelihood of finding micrometastases by IHC. IHC should not be used routinely in
      the evaluation of the SLN and caution should be used when basing treatment
      decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC
      only detected micrometastases.

PMID- 16409588
TI  - Impact of race on breast cancer in lower socioeconomic status women.
AB  - Lower socioeconomic status and lack of access to care are often implicated as
      plausible causes for African American women to present with later stage breast
      cancer than Caucasian women. Our objective is to determine if racial differences
      are present in newly diagnosed breast cancer in women of equivalent socioeconomic
      status. A retrospective review of prospectively gathered data from women with
      newly diagnosed breast cancer was performed. All women presented to the indigent
      (uninsured and below the poverty line) breast clinic for evaluation and treatment
      of their breast pathology. Data pertaining to epidemiologic factors, diagnosis,
      pathology, and treatment were collected. The data were analyzed by chi-squared
      and tailed t-tests. Between March 2002 and May 2004, 52 women (African
      American=36, Caucasian=16) were diagnosed with breast cancer at our clinic. The
      median age for both groups at presentation was 56.6 years. The staging assessment
      based on the pathologic size of the tumor was also equivalent between African
      American and Caucasian women at 2.29 cm and 2.21 cm, respectively. Metastatic
      lymph node involvement occurred in 14 women (African American=7, Caucasian=7),
      with 19.4% African American and 43.8% Caucasian being node positive (p=0.068). In
      fact, there were no statistically significant differences between the races for
      menarche, menopause, body mass index (BMI), duration of symptoms before
      presentation, type of diagnostic biopsy or surgery chosen, histology, receptor
      status, utilization of chemotherapy and radiation, and length of follow-up. The
      only statistical differences found were in the age of the first live birth
      (African American=19, Caucasian=22; p=0.028), the use of ultrasound in initial
      evaluation of a breast mass (less use in African American; p=0.012), and
      utilization of sentinel lymph node biopsy (Caucasian=75%, African American=42%;
      p=0.026). Breast cancer in African American women traditionally presents at a
      more advanced stage and with poor prognostic features. However, when matched for
      lower socioeconomic status, racial disparities essentially disappear.

PMID- 16409589
TI  - Long-term clinical and radiologic results with autologous fat transplantation for
      breast augmentation: case reports and review of the literature.
AB  - Autologous fat transplantation was initially performed by plastic surgeons for
      improving facial and body contour depressions and scars. There has been long
      standing interest in breast augmentation for cosmetic purposes and for the
      filling of defects from partial breast resection for breast cancer. In the 1980s,
      autologous fat transplantation for breast augmentation and symmetry gained
      popularity. We present two cases of autologous fat transplantation into the
      breast parenchyma that demonstrate the long-term clinical and radiologic results
      of this approach and to illustrate the potential caveats regarding breast cancer
      diagnosis in these patients. We also review the existing literature on the
      subject as it relates to long-term effects and complications.

PMID- 16409590
TI  - Fibromatosis of the breast: case report and current concepts in the management of
      an uncommon lesion.
AB  - Fibromatosis is an uncommon breast lesion that can mimic breast carcinoma in its
      clinical presentation. We present a case in which excisional biopsy was necessary
      to establish a diagnosis of fibromatosis. Clinical, diagnostic imaging, and
      pathologic features are discussed. Magnetic resonance imaging (MRI) has emerged
      as a tool for further characterization of breast lesions and as a screening
      modality in high-risk patient populations. Ours marks the second case in which
      dynamic MRI has been correlated with histologically confirmed primary mammary
      fibromatosis. Unlike the previous report, MRI in this case mimics breast
      carcinoma in its morphologic and pharmacokinetic features of enhancement. Wide
      local excision with clear margins remains the treatment of choice. Current data
      on radiotherapy and pharmacologic therapy for mammary fibromatosis are reviewed.

PMID- 16409591
TI  - Necrotizing fasciitis in a postmastectomy wound.
AB  - Necrotizing fasciitis is a rare, life-threatening condition, characterized by
      progressive gangrene of the subcutaneous tissue with subsequent death of the
      overlying skin. It is associated with a high mortality rate. We describe a
      patient who developed this condition after elective mastectomy and survived.
      Necrotizing fasciitis is known to occur in any part of the body, including the
      breast, and also following any kind of surgery, however, to the best of our
      knowledge this condition has never been described after a mastectomy. The
      diagnosis and management algorithm of this condition is discussed.

PMID- 16409592
TI  - Orbital metastasis as the first presentation of nonpalpable invasive lobular
      carcinoma of the breast.

PMID- 16409594
TI  - Rapid growth of an exophytic angiosarcoma of the breast.

PMID- 16409595
TI  - Paget's disease of the breast.

PMID- 16409593
TI  - Unilateral axillary adenopathy caused by Kikuchi-Fujimoto disease.

PMID- 16409596
TI  - Giant hamartoma of the breast.

PMID- 16409597
TI  - Mammographic appearance of microcalcifications: can they change after neoadjuvant
      chemotherapy?

PMID- 16409598
TI  - Increasing use of mammography improves the outcome of breast cancer in Finland.

PMID- 16409599
TI  - Conservative treatment with nipple-areolar resection for subareolar breast
      cancer.

PMID- 16409600
TI  - Symptomatic breast clinic: an efficient resource.

PMID- 16409601
TI  - A simple and quick method to evaluate mastalgia.

PMID- 16409602
TI  - Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumors:
      analysis of surgical aspects based on histological types.
AB  - BACKGROUND: The aim of this study was to evaluate whether hormonal functions of
      the tumor influence the operative results of laparoscopic adrenalectomy, and to
      analyse the clinical outcomes in patients with various hormonally active adrenal
      tumors. METHODS: Clinical and pathological records of 68 patients were reviewed.
      The average age of patients was 40 years (range 20-75); 39 were women and 29 men.
      For the comparison, patients were divided into the non-functioning tumor group (n
      = 22) and the functioning tumor group (n = 46). RESULTS: All laparoscopic
      adrenalectomies were finished successfully, and no open surgery was necessary.
      The median operative time and blood loss in the two groups were similar; however,
      in subgroup analysis, operative time for pheochromocytoma was significantly
      longer than that for non-functioning tumor (P = 0.044). No difference was noted
      in intra- and postoperative data between the groups. Of the 22 patients with
      aldosteronoma, 18 (81.8%) became normotensive and no longer required
      postoperative blood pressure medications. Adrenalectomy led to an overall
      reduction in the median number of antihypertensive medications (P < 0.001). All
      patients with Cushing adenoma had resolution or improvement of the signs and
      symptoms during follow-up periods. There was no evidence of biochemical or
      clinical recurrence in any patient with pheochromocytoma. CONCLUSION: The results
      of this retrospective review document that laparoscopic adrenalectomy is a safe
      and effective treatment for functioning as well as non-functioning adrenal
      tumors, although endocrinologic features may play a significant role.

PMID- 16409603
TI  - Clinical outcomes of laparoscopic adrenalectomy according to tumor size.
AB  - OBJECTIVES: In order to evaluate the indication and usefulness of laparoscopic
      adrenalectomy, clinical outcomes of laparoscopic adrenalectomy for patients with
      adrenal tumors were examined. Whether tumor size affects surgical outcome was
      analysed, along with the long-term clinical outcome for these patients. PATIENTS
      AND METHODS: A total of 63 patients with adrenal tumor underwent laparoscopic
      adrenalectomy in our institute between 1999 and 2003. A laparoscopic
      transperitoneal approach was used in all cases. Underlying pathologies comprised
      Cushing syndrome (n = 12), pheochromocytoma (n = 13), primary aldosteronism (n =
      21), non-functioning adenoma (n = 12) and others (n = 5). RESULTS: No open
      conversion was performed. Mean operative duration was 239 min, and mean estimated
      blood loss was 134 mL. Tumor diameter was significantly smaller for primary
      aldosteronism than for Cushing syndrome, which in turn was significantly smaller
      than for adrenocorticotropic hormone-independent macronodular hyperplasia
      (AIMAH). No significant differences in surgical outcome and postoperative
      recovery were noted between large (>or=5 cm) and small (<5 cm) tumors. Long-term
      clinical outcome was better for patients with pheochromocytoma or primary
      aldosteronism than for patients with Cushing syndrome. CONCLUSIONS: Laparoscopic
      adrenalectomy for benign tumor offers excellent surgical outcomes and
      convalescence. This is true for both small and large tumors.

PMID- 16409604
TI  - Dismembered pyeloplasty in children: a review of 5 years single center
      experience.
AB  - AIM: Dismembered pyeloplasty is the treatment of choice for significant
      ureteropelvic junction obstruction in children. In the present study, we review
      our experience in 103 pediatric patients and present the clinical
      characteristics, the surgical treatment and its complications and the long term
      results. METHODS: We have reviewed the medical charts of 103 consecutive patients
      who underwent dismembered pyeloplasty in a 5-year period, from 1997 to 2002.
      Preoperative data, short- and long-term complications and outcome were recorded.
      Imaging studies included urinary tract sonography and dynamic renal scans, the
      results of which were compared pre- and postoperatively. RESULTS: Most of our
      patients were boys (81%), diagnosed prenatally (78%). We had no major
      complications and acceptable incidence of minor complications. Postoperative
      outcome was excellent, with decreased hydronephrosis (81%), improved renal
      drainage (87%) and preserved or improved renal function (89%). CONCLUSION:
      Dismembered pyeloplasty can be performed with a low incidence of minor
      complications, no major complications and excellent long-term outcome.

PMID- 16409605
TI  - Factors affecting health-related quality of life among patients with lower
      urinary tract symptoms.
AB  - BACKGROUND: This study aimed to evaluate the association of factors such as pain,
      lower urinary tract symptoms (LUTS), anxiety, depression and psychiatric
      morbidity on health-related quality of life (HRQoL) of patients with LUTS.
      METHODS: A total of 227 patients with LUTS were recruited into the study. The
      patients were assessed on pain, LUTS, anxiety, depression, psychiatric morbidity
      and health-related quality of life (HRQoL) using standardized questionnaires.
      RESULTS: The study showed that after adjustment, age, pain, anxiety, depression,
      psychiatric morbidity and LUTS contributed 31%, 13%, 45%, 16% and 48%
      respectively to the variability of the physical, mental, social, global and
      overall HRQoL. CONCLUSION: Age, pain, psychiatric morbidity, anxiety and
      depression are associated with HRQoL among patients with LUTS.

PMID- 16409606
TI  - Bulbocavernosus muscle flap in the repair of complicated vesicovaginal fistula.
AB  - AIM: To investigate the transposition of the bulbocavernosus muscle flap for
      repairing complicated vesicovaginal fistulas. METHODS: Vesicovaginal fistulas
      were repaired via combined abdominal and perineal approaches. Through an
      abdominal approach, the fistula and surrounding scar tissue were excised
      thoroughly. A perineal incision was made between the orifices of the urethra and
      the vagina, dissecting until the fistula. The vaginal defect was closed through
      either the abdominal or the perineal approach depending upon its position.
      Through the abdominal approach, the bladder defect was closed in two layers with
      the suture lines vertical to each other. The bulbocavernosus muscle was freed
      through an incision between the labium majus pudendi and the labium minus
      pudenda, without damaging the pudendal vascular supply. The bulbocavernosus
      muscle flap was tunneled beneath the labium minus pudendi, and was sutured in
      place on the bladder wall over the fistula repair site. RESULTS: Nine patients
      with complicated vesicovaginal fistulas were treated using this technique. After
      surgery, no symptoms of vagina leakage, urinary incontinence, or urethral
      stricture were reported by any of the patients, and they reported normal sexual
      function. CONCLUSIONS: Transposition of the bulbocavernosus muscle flap is an
      excellent technique with low morbidity and high success rate for repairing
      complicated vesicovaginal fistulas.

PMID- 16409607
TI  - Prognostic factors in Fournier gangrene.
AB  - AIMS: Fournier gangrene is a rapidly progressive necrotizing fasciitis involving
      the genitalia. It can be treated with antibiotics and immediate debridement along
      with treatment of the predisposing condition. We evaluated the prognostic
      factors, clinical characteristics and treatment of patients of the Fournier
      gangrene. METHODS: The subjects were 40 male patients diagnosed with Fournier
      gangrene who visited Wonkwang University Hospital, Iksan, Korea between January
      1991 and December 2000. Their medical records were reviewed with respect to
      demographics, medical history, symptoms and signs, physical examination,
      laboratory data, bacteriology, extent of disease, clinical course, and therapy.
      The extent of disease was quantified for each patient using a modification of the
      diagram used to assess the extent of burns. RESULTS: The average age was 55.3
      years (range 29.6-92.8). Of the 40 patients, 11 died (36%) and 29 survived (64%).
      Anorectal infections were the underlying local disease most commonly associated
      with high mortality (75%). Although the most common associated illness was
      diabetes, it was not related to the prognosis (death rate: 20.0%). In contrast,
      the death rate was highest in chronic renal failure, reaching 50%. The mortality
      rate increased with the duration of symptoms before hospitalization. Patients
      with <6% surface area involvement were more likely to survive. On admission,
      serum blood urea nitrogen (s-BUN) and serum creatinine were significantly higher
      in the patients who died. CONCLUSION: Survival is associated significantly with
      anorectal infection, chronic renal failure, the duration of symptoms before
      hospitalization, the extent of gangrene, and s-BUN and creatinine level on
      admission.

PMID- 16409608
TI  - Retrospective study of 101 cases with incidental prostate cancer stages T1a and
      T1b.
AB  - PURPOSE: The purpose of this retrospective study was to clarify the character of
      incidental prostate cancer, stages T1a and T1b. METHODS: We analysed 101 cases of
      incidental prostate cancer. Incidental prostate cancer was diagnosed on the basis
      of normal digital rectal examination findings, a serum prostate-specific antigen
      (PSA) level of less than 4.0 ng/mL, and no abnormal computed tomography or
      ultrasonography findings. All patients were treated at Gifu University Hospital
      or an affiliated hospital during the period January 1992 through December 2001.
      RESULTS: There were 64 stage T1a cancers and 37 stage T1b cancers. The mean age
      of patients was 71.3 years (range 51-87 years). The mean serum PSA level was 1.63
      ng/mL (range 0.2-4.0 ng/mL). Thirty-five stage T1a patients (56.5%) and thirty
      two stage T1b patients (86.5%) underwent some type of treatment. Total
      prostatectomy was performed in eight stage T1a cases and fifteen stage T1b cases.
      Pathological diagnoses were as follows: pTx (n = 1), pT0 (n = 5) and pT2 (n = 2)
      for stage T1a cancers, and pT0 (n = 6), pT2 (n = 8) and pT3 (n = 1) for stage T1b
      cancers. Only one stage T1b cancer recurred. CONCLUSION: The outcome of patients
      with incidental prostate cancer was satisfactory; disease recurred in only one
      case of stage T1b cancer and there were no cases of PSA failure, although the
      pathological diagnosis in nine of the fifteen stage T1b cases (60.0%) treated
      with total prostatectomy was pT2 or pT3. Careful monitoring was indicated for
      stage T1a cancer, and some treatment was necessary for stage T1b cancer.

PMID- 16409609
TI  - Usefulness of ultrasensitive prostate-specific antigen assay for early detection
      of biochemical failure after radical prostatectomy.
AB  - BACKGROUND: In order to assess whether the prostate-specific antigen (PSA) nadir
      obtained with an ultrasensitive PSA assay can be used as a prognostic indicator
      for patients undergoing radical prostatectomy, we investigated it
      retrospectively. METHODS: Between October 1997 and July 2003, 46 patients
      underwent radical prostatectomy for prostate cancer at our institution. None of
      them received preoperative treatment. Levels of PSA were measured with an
      ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical
      recurrence was defined as a PSA level of 0.2 ng/mL or higher. RESULTS: There was
      a significant difference in PSA nadir between the biochemical recurrence group
      and the no recurrence group (P < 0.001). The receiver operating characteristics
      (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL,
      demonstrating a significant difference in biochemical recurrence after radical
      prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical
      failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed
      biochemical failure. CONCLUSION: The PSA nadir level obtained using an
      ultrasensitive PSA assay is an excellent predictor of biochemical recurrence
      after radical prostatectomy. Early detection of recurrence offers the possibility
      of early salvage therapy.

PMID- 16409610
TI  - Thoracoscopic transdiaphragmatic adrenalectomy for isolated locally recurrent
      adrenal carcinoma.
AB  - A 58-year-old man who had undergone left adrenalectomy 2 years previously for
      adrenocortical carcinoma was diagnosed to have a left suprarenal solid mass.
      Thoracoscopic transdiaphragmatic excision of the tumor was conducted under the
      diagnosis of isolated local recurrence of adrenal carcinoma. There were no
      intraoperative or postoperative complications. The patient subsequently received
      three courses of adjuvant chemotherapy. There have been no signs of tumor
      recurrence during 3 years follow up after surgery. This approach provides a
      minimally invasive alternative to an open thoracoabdominal procedure after prior
      open surgery.

PMID- 16409611
TI  - Renal brucelloma: a rare infection of the kidney.
AB  - We report a case of renal abscess caused by brucellosis (renal brucelloma) which
      was treated by surgery. Renal parenchymal involvement of systemic brucellosis is
      a very rare condition and relapses after medical treatment, such as solid organ
      abscess including kidney, should be especially considered. In chronic cases,
      laboratory findings including polymerase chain-reaction examination is needed for
      definitive diagnosis.

PMID- 16409612
TI  - Malignant retroperitoneal tumor arising in a multicystic dysplastic kidney of a
      girl with Schinzel-Giedion syndrome.
AB  - We report the first case of malignant retroperitoneal tumor arising in a
      multicystic dysplastic kidney of an 8-year-old girl with Schinzel-Giedion
      syndrome. Although conservative treatment has been regarded as the standard
      management for asymptomatic multicystic dysplastic kidney, prophylactic surgical
      removal should be considered for selected children with potential risk of
      malignancy.

PMID- 16409613
TI  - Chronic expanding hematoma in the psoas muscle.
AB  - We report an unusual case of chronic expanding hematoma in the psoas muscle. A 53
      year-old man was admitted for evaluation of a mass shadow in the left lower lung
      field on chest X-rays. He had also been suffering from dull left back pain. A
      computed tomography scan showed a cystic lesion with a rim enhancement in the
      left retroperitoneal space. Mixed signal intensity in a mosaic pattern was seen
      on a T2-weighted magnetic resonance image. We could not rule out a suspicion of a
      neoplastic intratumoral hemorrhage. Due to increased pain and the definite
      diagnosis, surgery was performed. Histopathological examination confirmed the
      diagnosis of chronic expanding hematoma. The expansion process is thought to be
      due to the irritant effects of blood and its breakdown products, which cause
      repeated exudation and bleeding from capillaries in the granulation tissues.

PMID- 16409614
TI  - Ectopic prostatic tissue in the bladder.
AB  - Ectopic prostatic tissue in the bladder has rarely been reported and usually
      involves the midline in the form of vestigial remains of embryonic prostatic
      elements. To our knowledge there are only 32 reports on this lesion in the
      literature in English. Prostatic heterotopia may be endoscopically confused with
      malignancy in the urinary system. We report three cases of ectopic prostatic
      tissue at the retrotrigonal area and left ureteral orifice. The patients
      presented with gross or microscopic hematuria and all the lesions had a polypoid
      appearance. The histopathologic and immunohistochemical examination revealed the
      prostatic nature of the tissue. No recurrences were evidenced. The authors review
      the literature concerning this lesion which should be recognized by urologists
      and pathologists, who must be aware of its benign nature.

PMID- 16409615
TI  - Two cases of female acute urinary retention caused by an impacted pelvic mass.
AB  - We report two cases of acute urinary retention in women with an impacted pelvic
      mass. In both cases, all urinary symptoms resolved completely after the surgical
      removal of the mass.

PMID- 16409616
TI  - Rupture of the superficial dorsal vein of the penis.
AB  - Unusual causes of acute penis, such as the rupture of a superficial vein of the
      penis, can mimic fractured penis. The diagnosis in such cases is mostly after
      exploration. The author describes a case where a high index of clinical suspicion
      led to the diagnosis of the rupture of a superficial dorsal vein of the penis
      without exploration. The patient had a successful recovery with conservative
      management.

PMID- 16409617
TI  - High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral
      blood stem cell transplantation for male germ cell tumor. Preliminary report.
AB  - AIM: To evaluate the feasibility and usefulness of high dose chemotherapy
      including paclitaxel (T-ICE) combined with peripheral blood stem cell
      transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients
      with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy
      including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin,
      1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses
      of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker
      levels decreased to within the normal range by T-ICE. Two patients underwent
      resection of residual tumor. In one patient, viable cancer cells were detected in
      resected lymph node tissue and adjuvant chemotherapy was then performed. Although
      the follow-up period was short (7-15.5 months), four of the five patients (80%)
      showed no evidence of recurrent disease. No significant differences in side
      effects were noted between T-ICE and conventional high dose ICE, which was
      previously performed in 39 patients at the Division of Urology, Kobe University
      Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy,
      including T-ICE, combined with PBSCT showed an almost identical degree of side
      effects as seen in previous high dose chemotherapy without paclitaxel. Although
      80% of the patients showed no evidence of disease so far, the efficacy of T-ICE
      should be evaluated with more patients and longer follow up.

PMID- 16409618
TI  - Laparoscopic ureterolysis for idiopathic retroperitoneal fibrosis.
AB  - Three patients with idiopathic retroperitoneal fibrosis underwent laparoscopic
      ureterolysis. Two patients were bilateral cases which were performed successfully
      as a one stage procedure. Another patient, who was unsuccessfully treated, had a
      long ureteral stricture. Laparoscopic ureterolysis may be a useful alternative to
      open surgical management especially in bilateral cases, except for patients with
      a long ureteral stricture.

PMID- 16409619
TI  - Utility of extracorporeal traction with nylon thread for easier vesicourethral
      anastomosis in laparoscopic prostatectomy.
AB  - PURPOSE: Vesicourethral anastomosis in laparoscopic prostatectomy is a very
      difficult procedure. Our purpose in this study was to evaluate a new method using
      extracorporeal bladder neck traction with nylon thread for vesicourethral
      anastomosis during laparoscopic radical prostatectomy. MATERIALS AND METHODS: A
      total of 10 patients underwent laparoscopic radical prostatectomy by this
      technique, and we evaluated anastomosis time, operative time, and postoperative
      status of vesicourethral anastomosis. RESULTS: It was possible to shorten both
      anastomosis time and operative time by this procedure, and to obtain a hermetic
      anastomosis without higher risk of incontinence, stricture, or leakage.
      CONCLUSIONS: Extracorporeal bladder neck traction with nylon thread is a very
      useful procedure to carry out easier vesicourethral anastomosis, especially for a
      surgeon's initial experience in laparoscopic radical prostatectomy.

PMID- 16409620
TI  - Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle
      relaxation in allergic asthma.
AB  - BACKGROUND: Using guinea pig tracheal preparations, we have recently shown that
      endogenous arginase activity attenuates inhibitory nonadrenergic noncholinergic
      (iNANC) nerve-mediated airway smooth muscle relaxation by reducing nitric oxide
      (NO) production--due to competition with neuronal NO-synthase (nNOS) for the
      common substrate, L-arginine. Furthermore, in a guinea pig model of allergic
      asthma, airway arginase activity is markedly increased after the early asthmatic
      reaction (EAR), leading to deficiency of agonist-induced, epithelium-derived NO
      and subsequent airway hyperreactivity. In this study, we investigated whether
      increased arginase activity after the EAR affects iNANC nerve-derived NO
      production and airway smooth muscle relaxation. METHODS: Electrical field
      stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5-16 Hz)-induced relaxation was measured
      in tracheal open-ring preparations precontracted to 30% with histamine in the
      presence of 1 microM atropine and 3 microM indomethacin. The contribution of NO
      to EFS-induced relaxation was assessed by the nonselective NOS inhibitor Nomega
      nitro-L-arginine (L-NNA, 100 microM), while the involvement of arginase activity
      in the regulation of EFS-induced NO production and relaxation was investigated by
      the effect of the specific arginase inhibitor Nomega-hydroxy-nor-L-arginine (nor
      NOHA, 10 microM). Furthermore, the role of substrate availability to nNOS was
      measured in the presence of exogenous L-arginine (5.0 mM). RESULTS: At 6 h after
      ovalbumin-challenge (after the EAR), EFS-induced relaxation (ranging from 3.2 +/-
      1.1% at 0.5 Hz to 58.5 +/- 2.2% at 16 Hz) was significantly decreased compared to
      unchallenged controls (7.1 +/- 0.8% to 75.8 +/- 0.7%; P < 0.05 all). In contrast
      to unchallenged controls, the NOS inhibitor L-NNA did not affect EFS-induced
      relaxation after allergen challenge, indicating that NO deficiency underlies the
      impaired relaxation. Remarkably, the specific arginase inhibitor nor-NOHA
      normalized the impaired relaxation to unchallenged control (P < 0.05 all), which
      effect was inhibited by L-NNA (P < 0.01 all). Moreover, the effect of nor-NOHA
      was mimicked by exogenous L-arginine. CONCLUSION: The results clearly demonstrate
      that increased arginase activity after the allergen-induced EAR contributes to a
      deficiency of iNANC nerve-derived NO and decreased airway smooth muscle
      relaxation, presumably via increased substrate competition with nNOS.

PMID- 16409622
TI  - Time series analysis of age related cataract hospitalizations and
      phacoemulsification.
AB  - BACKGROUND: Cataract surgery remains a commonly performed elective surgical
      procedure in the aging and the elderly. The purpose of this study was to utilize
      time series methodology to determine the temporal and seasonal variations and the
      strength of the seasonality in age-related (senile) cataract hospitalizations and
      phacoemulsification surgeries. METHODS: A retrospective, cross-sectional time
      series analysis was used to assess the presence and strength of seasonal and
      temporal patterns of age-related cataract hospitalizations and
      phacoemulsification surgeries from April 1, 1991 to March 31, 2002. Hospital
      admission rates for senile cataract (n = 70,281) and phacoemulsification (n =
      556,431) were examined to determine monthly rates of hospitalization per 100,000
      population. Time series methodology was then applied to the monthly aggregates.
      RESULTS: During the study period, age-related cataract hospitalizations in
      Ontario have declined from approximately 40 per 100,000 to only one per 100,000.
      Meanwhile, the use of phacoemulsification procedures has risen dramatically. The
      study found evidence of biannual peaks in both procedures during the spring and
      autumn months, and summer and winter troughs. Statistical analysis revealed
      significant overall seasonal patterns for both age-related cataract
      hospitalizations and phacoemulsifications (p < 0.01). CONCLUSION: This study
      illustrates the decline in age-related cataract hospitalizations in Ontario
      resulting from the shift to outpatient phacoemulsification surgery, and
      demonstrates the presence of biannual peaks (a characteristic indicative of
      seasonality), in hospitalization and phacoemulsification during the spring and
      autumn throughout the study period.

PMID- 16409621
TI  - Analysis of the human cytomegalovirus genomic region from UL146 through UL147A
      reveals sequence hypervariability, genotypic stability, and overlapping
      transcripts.
AB  - BACKGROUND: Although the sequence of the human cytomegalovirus (HCMV) genome is
      generally conserved among unrelated clinical strains, some open reading frames
      (ORFs) are highly variable. UL146 and UL147, which encode CXC chemokine
      homologues are among these variable ORFs. RESULTS: The region of the HCMV genome
      from UL146 through UL147A was analyzed in clinical strains for sequence
      variability, genotypic stability, and transcriptional expression. The UL146
      sequences in clinical strains from two geographically distant sites were assigned
      to 12 sequence groups that differ by over 60% at the amino acid level. The same
      groups were generated by sequences from the UL146-UL147 intergenic region and the
      UL147 ORF. In contrast to the high level of sequence variability among unrelated
      clinical strains, the sequences of UL146 through UL147A from isolates of the same
      strain were highly stable after repeated passage both in vitro and in vivo.
      Riboprobes homologous to these ORFs detected multiple overlapping transcripts
      differing in temporal expression. UL146 sequences are present only on the largest
      transcript, which also contains all of the downstream ORFs including UL148 and
      UL132. The sizes and hybridization patterns of the transcripts are consistent
      with a common 3'-terminus downstream of the UL132 ORF. Early-late expression of
      the transcripts associated with UL146 and UL147 is compatible with the potential
      role of CXC chemokines in pathogenesis associated with viral replication.
      CONCLUSION: Clinical isolates from two different geographic sites cluster in the
      same groups based on the hypervariability of the UL146, UL147, or the intergenic
      sequences, which provides strong evidence for linkage and no evidence for
      interstrain recombination within this region. The sequence of individual strains
      was absolutely stable in vitro and in vivo, which indicates that sequence drift
      is not a mechanism for the observed sequence hypervariability. There is also no
      evidence of transcriptional splicing, although multiple overlapping transcripts
      extending into the adjacent UL148 and UL132 open reading frames were detected
      using gene-specific probes.

PMID- 16409623
TI  - Impact of vaccine economic programs on physician referral of children to public
      vaccine clinics: a pre-post comparison.
AB  - BACKGROUND: The Vaccines for Children (VFC) Program is a major vaccine
      entitlement program with limited long-term evaluation. The objectives of this
      study are to evaluate the effect of VFC on physician reported referral of
      children to public health clinics and on doses administered in the public sector.
      METHODS: Minnesota and Pennsylvania primary care physicians (n = 164), completed
      surveys before (e.g., 1993) and after (2003) VFC, rating their likelihood on a
      scale of 0 (very unlikely) to 10 (very likely) of referring a child to the health
      department for immunization. RESULTS: The percentage of respondents likely to
      refer was 60% for an uninsured child, 14% for a child with Medicaid, and 3% for a
      child with insurance that pays for immunization. Half (55%) of the physicians who
      did not participate in VFC were likely to refer a Medicaid-insured child, as
      compared with 6% of those who participated (P < 0.001). Physician likelihood to
      refer an uninsured child for vaccination, measured on a scale of 0 to 10 where 10
      is very likely, decreased by a mean difference of 1.9 (P < 0.001) from pre- to
      post-VFC. The likelihood to refer a Medicaid-insured child decreased by a mean of
      1.2 (P = 0.001). CONCLUSION: Reported out-referral to public clinics decreased
      over time. In light of increasing immunizations rates, this suggests that more
      vaccines were being administered in private provider offices.

PMID- 16409624
TI  - Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for
      distinguishing between endocervical and endometrial mucinous adenocarcinoma.
AB  - BACKGROUND: Distinguishing endocervical adenocarcinoma (ECA) from endometrial
      mucinous adenocarcinoma (EMMA) is clinically significant in view of the
      differences in their management and prognosis. In this study, we used a panel of
      tumor markers to determine their ability to distinguish between primary
      endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma.
      METHODS: Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16,
      estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed
      to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored
      based on the percentage of staining pattern, apical, apical and cytoplasmic
      (A/C), or negative. For p16, cases were scored based on the percentage of cells
      stained. For the rest of the antibodies, semiquantitative scoring system was
      carried out. RESULTS: For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C
      staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of
      MUC1 expression in the two groups of malignancy was statistically significant (p
      < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%)
      EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%)
      EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%)
      EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with
      median and range of 0 (0-6), and 1.5 (0-9) respectively. CONCLUSION: A panel of
      immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is
      recommended, when there is morphological and clinical doubt as to the primary
      site of endocervical or endometrial origin.

PMID- 16409625
TI  - The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of
      secondary bone tumors: an intravital microscopy study in mice.
AB  - BACKGROUND: The inhibition of angiogenesis is a promising strategy for the
      treatment of malignant primary and secondary tumors in addition to established
      therapies such as surgery, chemotherapy, and radiation. There is strong
      experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition
      is a potent mechanism to reduce angiogenesis. For bone metastases which occur in
      up to 85% of the most frequent malignant primary tumors, the effects of Cox-2
      inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the
      aim of this study was to investigate the effects of Celecoxib, a selective Cox-2
      inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors.
      METHODS: In 10 male severe combined immunodeficient (SCID) mice, pieces of A549
      lung carcinomas were implanted into a newly developed cranial window preparation
      where the calvaria serves as the site for orthotopic implantation of the tumors.
      From day 8 after tumor implantation, five animals (Celecoxib) were treated daily
      with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the
      equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and
      growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis
      was quantified using the TUNEL assay. RESULTS: Treatment with Celecoxib reduced
      both microvessel density and tumor growth. TUNEL reaction showed an increase in
      apoptotic cell death of tumor cells after treatment with Celecoxib as compared to
      Controls. CONCLUSION: Celecoxib is a potent inhibitor of tumor growth of
      secondary bone tumors in vivo which can be explained by its anti-angiogenic and
      pro-apoptotic effects. The results indicate that a combination of established
      therapy regimes with Cox-2 inhibition represents a possible application for the
      treatment of bone metastases.

PMID- 16409626
TI  - Motor neuronopathy with dropped hands and downbeat nystagmus: a distinctive
      disorder? A case report.
AB  - BACKGROUND: Eye movements are clinically normal in most patients with motor
      neuron disorders until late in the disease course. Rare patients are reported to
      show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus.
      We report clinical and oculomotor findings in three patients with motor
      neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar
      disease. CASE PRESENTATION: All patients had clinical and electrodiagnostic
      features of anterior horn cell disease. Involvement of finger and wrist extensors
      predominated, causing finger and wrist drop. Bulbar or respiratory dysfunction
      did not occur. All three had clinically evident downbeat nystagmus worse on
      lateral and downgaze, confirmed on eye movement recordings using the magnetic
      search coil technique in two patients. Additional oculomotor findings included
      alternating skew deviation and intermittent horizontal saccadic oscillations, in
      one patient each. One patient had mild cerebellar atrophy, while the other two
      had no cerebellar or brainstem abnormality on neuroimaging. The disorder is
      slowly progressive, with survival up to 30 years from the time of onset.
      CONCLUSION: The combination of motor neuronopathy, characterized by early and
      prominent wrist and finger extensor weakness, and downbeat nystagmus with or
      without other cerebellar eye movement abnormalities may represent a novel motor
      neuron syndrome.

PMID- 16409627
TI  - Scoliosis treatment using spinal manipulation and the Pettibon Weighting System:
      a summary of 3 atypical presentations.
AB  - BACKGROUND: Given the relative lack of treatment options for mild to moderate
      scoliosis, when the Cobb angle measurements fall below the 25-30 degrees range,
      conservative manual therapies for scoliosis treatment have been increasingly
      investigated in recent years. In this case series, we present 3 specific cases of
      scoliosis. CASE PRESENTATION: Patient presentation, examination, intervention and
      outcomes are detailed for each case. The types of scoliosis presented here are
      left thoracic, idiopathic scoliosis after Harrington rod instrumentation, and a
      left thoracic scoliosis secondary to Scheuermann's Kyphosis. Each case carries
      its own clinical significance, in relation to clinical presentation. The first
      patient presented for chiropractic treatment with a 35 degrees thoracic
      dextroscoliosis 18 years following Harrington Rod instrumentation and fusion. The
      second patient presented with a 22 degrees thoracic levoscoliosis and concomitant
      Scheuermann's Disease. Finally, the third case summarizes the treatment of a
      patient with a primary 37 degrees idiopathic thoracic levoscoliosis. Each patient
      was treated with a novel active rehabilitation program for varying lengths of
      time, including spinal manipulation and a patented external head and body
      weighting system. Following a course of treatment, consisting of clinic and home
      care treatments, post-treatment radiographs and examinations were conducted.
      Improvement in symptoms and daily function was obtained in all 3 cases.
      Concerning Cobb angle measurements, there was an apparent reduction in Cobb angle
      of 13 degrees , 8 degrees , and 16 degrees over a maximum of 12 weeks of
      treatment. CONCLUSION: Although mild to moderate reductions in Cobb angle
      measurements were achieved in these cases, these improvements may not be related
      to the symptomatic and functional improvements. The lack of a control also
      includes the possibility of a placebo effect. However, this study adds to the
      growing body of literature investigating methods by which mild to moderate cases
      of scoliosis can be treated conservatively. Further investigation is necessary to
      determine whether curve reduction and/or manipulation and/or placebo was
      responsible for the symptomatic and functional improvements noted in these cases.

PMID- 16409628
TI  - Automatic discovery of cross-family sequence features associated with protein
      function.
AB  - BACKGROUND: Methods for predicting protein function directly from amino acid
      sequences are useful tools in the study of uncharacterized protein families and
      in comparative genomics. Until now, this problem has been approached using
      machine learning techniques that attempt to predict membership, or otherwise, to
      predefined functional categories or subcellular locations. A potential drawback
      of this approach is that the human-designated functional classes may not
      accurately reflect the underlying biology, and consequently important sequence-to
      function relationships may be missed. RESULTS: We show that a self-supervised
      data mining approach is able to find relationships between sequence features and
      functional annotations. No preconceived ideas about functional categories are
      required, and the training data is simply a set of protein sequences and their
      UniProt/Swiss-Prot annotations. The main technical aspect of the approach is the
      co-evolution of amino acid-based regular expressions and keyword-based logical
      expressions with genetic programming. Our experiments on a strictly non-redundant
      set of eukaryotic proteins reveal that the strongest and most easily detected
      sequence-to-function relationships are concerned with targeting to various
      cellular compartments, which is an area already well studied both experimentally
      and computationally. Of more interest are a number of broad functional roles
      which can also be correlated with sequence features. These include inhibition,
      biosynthesis, transcription and defence against bacteria. Despite substantial
      overlaps between these functions and their corresponding cellular compartments,
      we find clear differences in the sequence motifs used to predict some of these
      functions. For example, the presence of polyglutamine repeats appears to be
      linked more strongly to the "transcription" function than to the general
      "nuclear" function/location. CONCLUSION: We have developed a novel and useful
      approach for knowledge discovery in annotated sequence data. The technique is
      able to identify functionally important sequence features and does not require
      expert knowledge. By viewing protein function from a sequence perspective, the
      approach is also suitable for discovering unexpected links between biological
      processes, such as the recently discovered role of ubiquitination in
      transcription.

PMID- 16409630
TI  - Enzymes: An integrated view of structure, dynamics and function.
AB  - Microbes utilize enzymes to perform a variety of functions. Enzymes are
      biocatalysts working as highly efficient machines at the molecular level. In the
      past, enzymes have been viewed as static entities and their function has been
      explained on the basis of direct structural interactions between the enzyme and
      the substrate. A variety of experimental and computational techniques, however,
      continue to reveal that proteins are dynamically active machines, with various
      parts exhibiting internal motions at a wide range of time-scales. Increasing
      evidence also indicates that these internal protein motions play a role in
      promoting protein function such as enzyme catalysis. Moreover, the
      thermodynamical fluctuations of the solvent, surrounding the protein, have an
      impact on internal protein motions and, therefore, on enzyme function. In this
      review, we describe recent biochemical and theoretical investigations of internal
      protein dynamics linked to enzyme catalysis. In the enzyme cyclophilin A,
      investigations have lead to the discovery of a network of protein vibrations
      promoting catalysis. Cyclophilin A catalyzes peptidyl-prolyl cis/trans
      isomerization in a variety of peptide and protein substrates. Recent studies of
      cyclophilin A are discussed in detail and other enzymes (dihydrofolate reductase
      and liver alcohol dehydrogenase) where similar discoveries have been reported are
      also briefly discussed. The detailed characterization of the discovered networks
      indicates that protein dynamics plays a role in rate-enhancement achieved by
      enzymes. An integrated view of enzyme structure, dynamics and function have wide
      implications in understanding allosteric and co-operative effects, as well as
      protein engineering of more efficient enzymes and novel drug design.

PMID- 16409629
TI  - Anti-viral RNA silencing: do we look like plants?
AB  - The anti-viral function of RNA silencing was first discovered in plants as a
      natural manifestation of the artificial 'co-suppression', which refers to the
      extinction of endogenous gene induced by homologous transgene. Because silencing
      components are conserved among most, if not all, eukaryotes, the question rapidly
      arose as to determine whether this process fulfils anti-viral functions in
      animals, such as insects and mammals. It appears that, whereas the anti-viral
      process seems to be similarly conserved from plants to insects, even in worms,
      RNA silencing does influence the replication of mammalian viruses but in a
      particular mode: micro(mi)RNAs, endogenous small RNAs naturally implicated in
      translational control, rather than virus-derived small interfering (si)RNAs like
      in other organisms, are involved. In fact, these recent studies even suggest that
      RNA silencing may be beneficial for viral replication. Accordingly, several large
      DNA mammalian viruses have been shown to encode their own miRNAs. Here, we
      summarize the seminal studies that have implicated RNA silencing in viral
      infection and compare the different eukaryotic responses.

PMID- 16409632
TI  - Development of a new bicistronic retroviral vector with strong IRES activity.
AB  - BACKGROUND: Internal Ribosome Entry Site (IRES)-based bicistronic vectors are
      important tools in today's cell biology. Among applications, the expression of
      two proteins under the control of a unique promoter permits the monitoring of
      expression of a protein whose biological function is being investigated through
      the observation of an easily detectable tracer, such as Green Fluorescent Protein
      (GFP). However, analysis of published results making use of bicistronic vectors
      indicates that the efficiency of the IRES-controlled expression can vary widely
      from one vector to another, despite their apparent identical IRES sequences. We
      investigated the molecular basis for these discrepancies. RESULTS: We observed up
      to a 10 fold difference in IRES-controlled expression from distinct bicistronic
      expression vectors harboring the same apparent IRES sequences. We show that the
      insertion of a HindIII site, in place of the initiating AUG codon of the wild
      type EMCV IRES, is responsible for the dramatic loss of expression from the
      second cistron, whereas expression from the first cistron remains unaffected.
      Thus, while the replacement of the authentic viral initiating AUG by a HindIII
      site results in the theoretical usage of the initiation codon of the HindIII
      subcloned cDNA, the subsequent drop of expression dramatically diminishes the
      interest of the bicistronic structure. Indeed, insertion of the HindIII site has
      such a negative effect on IRES function that detection of the IRES-controlled
      product can be difficult, and sometimes even below the levels of detection. It is
      striking to observe that this deleterious modification is widely found in
      available IRES-containing vectors, including commercial ones, despite early
      reports in the literature stating the importance of the integrity of the
      initiation codon for optimal IRES function. CONCLUSION: From these observations,
      we engineered a new vector family, pPRIG, which respects the EMCV IRES structure,
      and permits easy cloning, tagging, sequencing, and expression of any cDNA in the
      first cistron, while keeping a high level of expression from its IRES-dependent
      second cistron (here encoding eGFP).

PMID- 16409631
TI  - Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse
      transcription complexes determines their capacity to integrate into chromatin.
AB  - BACKGROUND: The early events of the HIV-1 life cycle include entry of the viral
      core into target cell, assembly of the reverse transcription complex (RTCs)
      performing reverse transcription, its transformation into integration-competent
      complexes called pre-integration complexes (PICs), trafficking of complexes into
      the nucleus, and finally integration of the viral DNA into chromatin. Molecular
      details and temporal organization of these processes remain among the least
      investigated and most controversial problems in the biology of HIV. RESULTS: To
      quantitatively evaluate maturation and nuclear translocation of the HIV-1 RTCs,
      nucleoprotein complexes isolated from the nucleus (nRTC) and cytoplasm (cRTC) of
      HeLa cells infected with MLV Env-pseudotyped HIV-1 were analyzed by real-time
      PCR. While most complexes completed reverse transcription in the cytoplasm, some
      got into the nucleus before completing DNA synthesis. The HIV-specific RNA
      complexes could get into the nucleus when reverse transcription was blocked by
      reverse transcriptase inhibitor, although nuclear import of RNA complexes was
      less efficient than of DNA-containing RTCs. Analysis of the RTC nuclear import in
      synchronized cells infected in the G2/M phase of the cell cycle showed enrichment
      in the nuclei of RTCs containing incomplete HIV-1 DNA compared to non
      synchronized cells, where RTCs with complete reverse transcripts prevailed.
      Immunoprecipitation assays identified viral proteins IN, Vpr, MA, and cellular
      Ini1 and PML associated with both cRTCs and nRTCs, whereas CA was detected only
      in cRTCs and RT was diminished in nRTCs. Cytoplasmic maturation of the complexes
      was associated with increased immunoreactivity with anti-Vpr and anti-IN
      antibodies, and decreased reactivity with antibodies to RT. Both cRTCs and nRTCs
      carried out endogenous reverse transcription reaction in vitro. In contrast to
      cRTCs, in vitro completion of reverse transcription in nRTCs did not increase
      their integration into chromatin. CONCLUSION: These results suggest that RTC
      maturation occurs predominantly in the cytoplasm. Immature RTCs containing RT and
      incomplete DNA can translocate into the nucleus during mitosis and complete
      reverse transcription, but are defective for integration.

PMID- 16409633
TI  - Prediction of depression in European general practice attendees: the PREDICT
      study.
AB  - BACKGROUND: Prevention of depression must address multiple risk factors.
      Estimating overall risk across a range of putative risk factors is fundamental to
      prevention of depression. However, we lack reliable and valid methods of risk
      estimation. This protocol paper introduces PREDICT, an international research
      study to address this risk estimation. METHODS/DESIGN: This is a prospective
      study in which consecutive general practice attendees in six European countries
      are recruited and followed up after six and 12 months. Prevalence of depression
      is assessed at baseline and each follow-up point. Consecutive attendees between
      April 2003 and September 2004 who were aged 18 to 75 were asked to take part. The
      possibility of a depressive episode was assessed using the Depression Section of
      the Composite International Diagnostic Interview. A selection of presumed risk
      factors was based on our previous work and a systematic review of the literature.
      It was necessary to evaluate the test-retest reliability of a number of risk
      factor questions that were developed specifically, or adapted, for the PREDICT
      study. In a separate reliability study conducted between January and November
      2003, consecutive general practice attendees in the six participating European
      countries completed the risk factor items on two occasions, two weeks apart. The
      overall response rate at entry to the study was 69%. We exceeded our expected
      recruitment rate, achieving a total of 10,048 people in all. Reliability
      coefficients were generally good to excellent. DISCUSSION: Response rate to
      follow-up in all countries was uniformly high, which suggests that prediction
      will be based on almost a full cohort. The results of our reliability analysis
      are encouraging and suggest that data collected during the course of PREDICT will
      have a satisfactory level of stability. The development of a multi-factor risk
      score for depression will lay the foundation for future research on risk
      reduction in primary care. Our data will also provide the necessary evidence base
      on which to develop and evaluate interventions to reduce the prevalence of
      depression.

PMID- 16409635
TI  - An approach for clustering gene expression data with error information.
AB  - BACKGROUND: Clustering of gene expression patterns is a well-studied technique
      for elucidating trends across large numbers of transcripts and for identifying
      likely co-regulated genes. Even the best clustering methods, however, are
      unlikely to provide meaningful results if too much of the data is unreliable.
      With the maturation of microarray technology, a wealth of research on statistical
      analysis of gene expression data has encouraged researchers to consider error and
      uncertainty in their microarray experiments, so that experiments are being
      performed increasingly with repeat spots per gene per chip and with repeat
      experiments. One of the challenges is to incorporate the measurement error
      information into downstream analyses of gene expression data, such as traditional
      clustering techniques. RESULTS: In this study, a clustering approach is presented
      which incorporates both gene expression values and error information about the
      expression measurements. Using repeat expression measurements, the error of each
      gene expression measurement in each experiment condition is estimated, and this
      measurement error information is incorporated directly into the clustering
      algorithm. The algorithm, CORE (Clustering Of Repeat Expression data), is
      presented and its performance is validated using statistical measures. By using
      error information about gene expression measurements, the clustering approach is
      less sensitive to noise in the underlying data and it is able to achieve more
      accurate clusterings. Results are described for both synthetic expression data as
      well as real gene expression data from Escherichia coli and Saccharomyces
      cerevisiae. CONCLUSION: The additional information provided by replicate gene
      expression measurements is a valuable asset in effective clustering. Gene
      expression profiles with high errors, as determined from repeat measurements, may
      be unreliable and may associate with different clusters, whereas gene expression
      profiles with low errors can be clustered with higher specificity. Results
      indicate that including error information from repeat gene expression
      measurements can lead to significant improvements in clustering accuracy.

PMID- 16409636
TI  - Quality research in healthcare: are researchers getting enough statistical
      support?
AB  - BACKGROUND: Reviews of peer-reviewed health studies have highlighted problems
      with their methodological quality. As published health studies form the basis of
      many clinical decisions including evaluation and provisions of health services,
      this has scientific and ethical implications. The lack of involvement of
      methodologists (defined as statisticians or quantitative epidemiologists) has
      been suggested as one key reason for this problem and this has been linked to the
      lack of access to methodologists. This issue was highlighted several years ago
      and it was suggested that more investments were needed from health care
      organisations and Universities to alleviate this problem. METHODS: To assess the
      current level of methodological support available for health researchers in
      England, we surveyed the 25 National Health Services Trusts in England, that are
      the major recipients of the Department of Health's research and development (R&D)
      support funding. RESULTS AND DISCUSSION: The survey shows that the earmarking of
      resources to provide appropriate methodological support to health researchers in
      these organisations is not widespread. Neither the level of R&D support funding
      received nor the volume of research undertaken by these organisations showed any
      association with the amount they spent in providing a central resource for
      methodological support for their researchers. CONCLUSION: The promotion and
      delivery of high quality health research requires that organisations hosting
      health research and their academic partners put in place funding and systems to
      provide appropriate methodological support to ensure valid research findings. If
      resources are limited, health researchers may have to rely on short courses
      and/or a limited number of advisory sessions which may not always produce
      satisfactory results.

PMID- 16409634
TI  - Humoral immune response to MUC5AC in patients with colorectal polyps and
      colorectal carcinoma.
AB  - BACKGROUND: MUC5AC is a secreted mucin aberrantly expressed by colorectal polyps
      and carcinoma. It has been hypothesized that aberrant expression of MUC5AC in
      colorectal carcinoma tissues increased the overall survival of patients with
      colorectal carcinoma. The present study investigates the incidence of naturally
      occurring MUC5AC antibodies in the sera of normal individuals, patients with
      colonic polyps and patients with advanced colorectal carcinoma. A second aim was
      to determine the relationship of MUC5AC antibody with the prognosis of colorectal
      carcinoma. METHODS: Free circulating MUC5AC antibodies were measured using an
      enzyme-linked immunosorbent assay with a synthetic peptide corresponding to an 8
      aa. segment of MUC5AC tandem repeat region. Immunohistochemical analysis was
      completed to demonstrate MUC5AC expression in the polyp specimens. RESULTS:
      MUC5AC antibodies were detected in 6 of 22 (27.3%) healthy subjects, 9 of 20
      (45%) polyp patients, 18 of 30 (60%) patients with colorectal cancer. The
      presence of circulating free MUC5AC antibody levels was significantly correlated
      with expression of MUC5AC in polyp sections. Serum MUC5AC antibody positivity was
      higher in patients with colon located tumors, advanced stage and poorly
      differentiated tumors were found negatively affecting patient survival in our
      study. MUC5AC antibody positivity was higher in patients with poor prognostic
      parameters. Disease free survival and overall survival were shorter in this group
      of patients. In the multivariate analysis MUC5AC antibody positivity didn't find
      an independent prognostic factor on prognosis. CONCLUSION: Decreased survival in
      colorectal carcinoma patients with MUC5AC antibody positivity may be due to a
      decrease in the MUC5AC expression in tumor tissues of surviving carcinoma
      patients.

PMID- 16409637
TI  - Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after
      peripheral nerve injury.
AB  - BACKGROUND: NF-kappaB binds to the kappaB motif to regulate transcription of
      genes involved in growth, immunity and inflammation, and plays a pivotal role in
      the production of pro-inflammatory cytokines after nerve injuries. The zinc
      finger protein ZAS3 also binds to the kappaB or similar motif. In addition to
      competition for common DNA sites, in vitro experiments have shown that ZAS3 can
      inhibit NF-kappaB via the association with TRAF2 to inhibit the nuclear
      translocation of NF-kappaB. However, the physiological significance of the ZAS3
      mediated inhibition of NF-kappaB has not been demonstrated. The purpose of this
      study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve
      ligation, a neuropathic pain model, to demonstrate a functional relationship
      between ZAS3 and NF-kappaB. RESULTS: Immunohistochemical experiments show that
      ZAS3 is expressed in specific regions of the central and peripheral nervous
      system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal
      formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions
      are also found in the cerebral cortex and in the grey matter of the spinal cord.
      In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons
      and astrocytes. Together with results of Western blot analyses, the data suggest
      that ZAS3 protein isoforms with differential cellular distribution are produced
      in a cell-specific manner. Further, neuropathic pain confirmed by persistent
      mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar
      spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3
      and an increase in the p65 subunit of NF-kappaB were observed in dorsal root
      ganglion ipsilateral to the ligation when compared to the contralateral side.
      CONCLUSION: ZAS3 is expressed in nervous tissues involved in cognitive function
      and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury
      may lead to activation of NF-kappaB, allowing Wallerian regeneration and
      induction of NF-kappaB-dependent gene expression, including pro-inflammatory
      cytokines. We propose that reciprocal changes in the expression of ZAS3 and NF
      kappaB might generate neuropathic pain after peripheral nerve injury.

PMID- 16409639
TI  - Bioinformatic analysis of an unusual gene-enzyme relationship in the arginine
      biosynthetic pathway among marine gamma proteobacteria: implications concerning
      the formation of N-acetylated intermediates in prokaryotes.
AB  - BACKGROUND: The N-acetylation of L-glutamate is regarded as a universal metabolic
      strategy to commit glutamate towards arginine biosynthesis. Until recently, this
      reaction was thought to be catalyzed by either of two enzymes: (i) the classical
      N-acetylglutamate synthase (NAGS, gene argA) first characterized in Escherichia
      coli and Pseudomonas aeruginosa several decades ago and also present in
      vertebrates, or (ii) the bifunctional version of ornithine acetyltransferase
      (OAT, gene argJ) present in Bacteria, Archaea and many Eukaryotes. This paper
      focuses on a new and surprising aspect of glutamate acetylation. We recently
      showed that in Moritella abyssi and M. profunda, two marine gamma proteobacteria,
      the gene for the last enzyme in arginine biosynthesis (argH) is fused to a short
      sequence that corresponds to the C-terminal, N-acetyltransferase-encoding domain
      of NAGS and is able to complement an argA mutant of E. coli. Very recently, other
      authors identified in Mycobacterium tuberculosis an independent gene
      corresponding to this short C-terminal domain and coding for a new type of NAGS.
      We have investigated the two prokaryotic Domains for patterns of gene-enzyme
      relationships in the first committed step of arginine biosynthesis. RESULTS: The
      argH-A fusion, designated argH(A), and discovered in Moritella was found to be
      present in (and confined to) marine gamma proteobacteria of the Alteromonas- and
      Vibrio-like group. Most of them have a classical NAGS with the exception of
      Idiomarina loihiensis and Pseudoalteromonas haloplanktis which nevertheless can
      grow in the absence of arginine and therefore appear to rely on the arg(A)
      sequence for arginine biosynthesis. Screening prokaryotic genomes for virtual
      argH-X 'fusions' where X stands for a homologue of arg(A), we retrieved a large
      number of Bacteria and several Archaea, all of them devoid of a classical NAGS.
      In the case of Thermus thermophilus and Deinococcus radiodurans, the arg(A)-like
      sequence clusters with argH in an operon-like fashion. In this group of
      sequences, we find the short novel NAGS of the type identified in M.
      tuberculosis. Among these organisms, at least Thermus, Mycobacterium and
      Streptomyces species appear to rely on this short NAGS version for arginine
      biosynthesis. CONCLUSION: The gene-enzyme relationship for the first committed
      step of arginine biosynthesis should now be considered in a new perspective. In
      addition to bifunctional OAT, nature appears to implement at least three
      alternatives for the acetylation of glutamate. It is possible to propose
      evolutionary relationships between them starting from the same ancestral N
      acetyltransferase domain. In M. tuberculosis and many other bacteria, this domain
      evolved as an independent enzyme, whereas it fused either with a carbamate kinase
      fold to give the classical NAGS (as in E. coli) or with argH as in marine gamma
      proteobacteria. Moreover, there is an urgent need to clarify the current
      nomenclature since the same gene name argA has been used to designate
      structurally different entities. Clarifying the confusion would help to prevent
      erroneous genomic annotation.

PMID- 16409640
TI  - Learning while evaluating: the use of an electronic evaluation portfolio in a
      geriatric medicine clerkship.
AB  - BACKGROUND: Electronic evaluation portfolios may play a role in learning and
      evaluation in clinical settings and may complement other traditional evaluation
      methods (bedside evaluations, written exams and tutor-led evaluations). METHODS:
      133 third-year medical students used the McGill Electronic Evaluation Portfolio
      (MEEP) during their one-month clerkship rotation in Geriatric Medicine between
      September 2002 and September 2003. Students were divided into two groups, one who
      received an introductory hands-on session about the electronic evaluation
      portfolio and one who did not. Students' marks in their portfolios were compared
      between both groups. Additionally, students self-evaluated their performance and
      received feedback using the electronic portfolio during their mandatory clerkship
      rotation. Students were surveyed immediately after the rotation and at the end of
      the clerkship year. Tutors' opinions about this method were surveyed once.
      Finally, the number of evaluations/month was quantified. In all surveys, Likert
      scales were used and were analyzed using Chi-square tests and t-tests to assess
      significant differences in the responses from surveyed subjects. RESULTS: The
      introductory session had a significant effect on students' portfolio marks as
      well as on their comfort using the system. Both tutors and students reported
      positive notions about the method. Remarkably, an average (+/- SD) of 520 (+/-
      70) evaluations/month was recorded with 30 (+/- 5) evaluations per student/month.
      CONCLUSION: The MEEP showed a significant and positive effect on both students'
      self-evaluations and tutors' evaluations involving an important amount of self
      reflection and feedback which may complement the more traditional evaluation
      methods.

PMID- 16409642
TI  - Refractile superficial retinal crystals and chronic retinal detachment: case
      report.
AB  - BACKGROUND: Few previous reports have described the presence of retinal
      refractile opacities at the macular area in patients presenting with longstanding
      peripheral retinal detachment. The exact nature of these opacities is unknown.
      CASE PRESENTATION: Two patients were referred with an abnormal appearance of
      refractile opacities in the macular area noted during routine examination. Both
      were found to have longstanding peripheral retinal detachments. Subretinal fluid
      analysis of one patient revealed the presence of multiple birefringent crystals.
      We hypothesise that these crystals are the origin of the refractile macular
      opacities noted. CONCLUSION: This report describes the rare presentation of
      asymptomatic peripheral retinal detachment by the detection of refractile macular
      opacities on routine examination. It highlights the importance of meticulous
      peripheral retinal examination in these cases. The article also describes the
      findings of the subretinal fluid analysis and discusses the possible hypothesis
      behind their appearance.

PMID- 16409641
TI  - Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting
      fiber volleys.
AB  - BACKGROUND: Anesthetic-induced CNS depression is thought to involve reduction of
      glutamate release from nerve terminals. Recent studies suggest that isoflurane
      reduces glutamate release by block of Na channels. To further investigate this
      question we examined the actions of isoflurane, TTX, extracellular Ca2+, CNQX and
      stimulus voltage (stim) on glutamate-mediated transmission at hippocampal
      excitatory synapses. EPSPs were recorded from CA1 neurons in rat hippocampal
      brain slices in response to Schaffer-collateral fiber stimulation. RESULTS:
      Isoflurane (350 microM; 1 MAC) reversibly depressed EPSP amplitudes by ~60% while
      facilitation increased approximately 20%. Consistent with previous studies, these
      results indicate a presynaptic site of action that involves reduced excitation
      release coupling. EPSPs were depressed to comparable levels by TTX (60 nM) or
      lowered stim, but facilitation was not changed, indicating a simple failure of
      axonal conduction. Similarly, partial antagonism of postsynaptic glutamate
      receptors with CNQX (10 microM) depressed EPSP amplitudes with no change in
      facilitation. However, EPSP depression by low external Ca2+ (0.8 mM) was
      accompanied by an increase in facilitation comparable to isoflurane. Isoflurane
      depression of EPSP amplitudes could also be partly reversed by high external Ca2+
      (4 mM) that also decreased facilitation. Isoflurane or low Ca2+ markedly reduced
      the slopes of fiber volley (FV)-EPSP input-output curves, consistent with little
      or no effect on FVs. By contrast, TTX didn't alter the FV-EPSP curve slope,
      indicating that EPSP depression resulted from FV depression. FVs were remarkably
      resistant to isoflurane. Somatic spike currents were unaffected by 350 microM (1
      MAC) isoflurane as well. The EC50 for isoflurane depression of FVs was
      approximately 2.8 mM (12 vol. %; 8 MAC). CONCLUSION: Isoflurane appears to
      depress CA1 synapses at presynaptic sites downstream from Na channels, as evident
      by the increased facilitation that accompanies EPSP depression. Fiber volleys did
      not exhibit depression by isoflurane, as has been reported for other brain
      regions.

PMID- 16409644
TI  - In silico discovery of human natural antisense transcripts.
AB  - BACKGROUND: Several high-throughput searches for potential natural antisense
      transcripts (NATs) have been performed recently, but most of the reports were
      focused on cis type. A thorough in silico analysis of human transcripts will help
      expand our knowledge of NATs. RESULTS: We have identified 568 NATs from human
      RefSeq RNA sequences. Among them, 403 NATs are reported for the first time, and
      at least 157 novel NATs are trans type. According to the pairing region of a
      sense and antisense RNA pair, hNATs are divided into 6 classes, of which about
      87% involve 5' or 3' UTR sequences, supporting the regulatory role of UTRs. Among
      a total of 535 NAT pairs related with splice variants, 77.4% (414/535) have their
      pairing regions affected or completely eliminated by alternative splicing,
      suggesting significant relationship of alternative splicing and antisense
      directed regulation. The extensive occurrence of splice variants in hNATs and
      other multiple pairing patterns results in a one-to-many relationship, allowing
      the formation of complex regulation networks. Based on microarray data from
      Stanford Microarray Database, two hNAT pairs were found to display significant
      inverse expression patterns before and after insulin injection. CONCLUSION: NATs
      might carry out more extensive and complex functions than previously thought.
      Combined with endogenous micro RNAs, hNATs could be regarded as a special group
      of transcripts contributing to the complex regulation networks.

PMID- 16409643
TI  - SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1
      LTR.
AB  - BACKGROUND: Tax is the oncoprotein of HTLV-1 which deregulates signal
      transduction pathways, transcription of genes and cell cycle regulation of host
      cells. Transacting function of Tax is mainly mediated by its protein-protein
      interactions with host cellular factors. As to Tax-mediated regulation of gene
      expression of HTLV-1 and cellular genes, Tax was shown to regulate histone
      acetylation through its physical interaction with histone acetylases and
      deacetylases. However, functional interaction of Tax with histone
      methyltransferases (HMTase) has not been studied. Here we examined the ability of
      Tax to interact with a histone methyltransferase SUV39H1 that methylates histone
      H3 lysine 9 (H3K9) and represses transcription of genes, and studied the
      functional effects of the interaction on HTLV-1 gene expression. RESULTS: Tax was
      shown to interact with SUV39H1 in vitro, and the interaction is largely dependent
      on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect
      the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing
      complex in the nuclei. In reporter gene assays, co-expression of SUV39H1
      represses Tax transactivation of HTLV-1 LTR promoter activity, which was
      dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1
      expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation
      (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but
      not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc
      plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1
      transformed and latently infected cell lines. CONCLUSION: Our study revealed for
      the first time the interaction between Tax and SUV39H1 and apparent tethering of
      SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of
      SUV39H1 to the LTR and induction of the repressive histone modification on the
      chromatin through H3 K9 methylation may be the basis for the dose-dependent
      repression of Tax transactivation of LTR by SUV39H1. Tax-induced SUV39H1
      expression, Tax-SUV39H1 interaction and tethering to the LTR may provide a
      support for an idea that the above sequence of events may form a negative
      feedback loop that self-limits HTLV-1 viral gene expression in infected cells.

PMID- 16409645
TI  - Vaccines for cervical cancer.
AB  - The review focuses on current and future prevention of invasive cervical cancer
      (ICC), the second most common cancer among women worldwide. Implementation of
      population-based cytological screening programmes, using the 'Pap' smear to
      detect pre-cancerous lesions in the cervix, has resulted in substantial declines
      in mortality and morbidity from ICC in North America and some European countries.
      However, cases of, and deaths from, ICC continue to occur. Primary prevention of
      infection with high-risk human papillomavirus (HPV) types, the central causal
      factor of ICC, could further reduce incidence of and mortality from ICC. This is
      particularly the case in developing countries, which bear 80% of the burden of
      ICC, and where effective Pap screening programmes are extremely difficult to
      implement. Very promising results from several trials of synthetic HPV type
      specific monovalent (HPV 16) and bivalent (HPV 16 and 18) vaccines have recently
      been published, showing high efficacy against type-specific persistent HPV
      infection and development of type-specific pre-cancerous lesions. Large-scale
      phase III trials of a number of such vaccine candidates are currently underway,
      and there is real hope that an effective vaccine capable of protecting against
      infection with HPV types 16 and 18 (which together account for approximately 70%
      of cervical cancer cases worldwide), and thereby of preventing development of a
      very significant proportion of cases of ICC, could be available within the next 2
      years.

PMID- 16409646
TI  - Can syndromic surveillance data detect local outbreaks of communicable disease? A
      model using a historical cryptosporidiosis outbreak.
AB  - A national UK surveillance system currently uses data from a health helpline (NHS
      Direct) in an attempt to provide early warning of a bio-terrorist attack, or an
      outbreak caused by a more common infection. To test this syndromic surveillance
      system we superimposed data from a historical outbreak of cryptosporidiosis onto
      a statistical model of NHS Direct call data. We modelled whether calls about
      diarrhoea (a proxy for cryptosporidiosis) exceeded a statistical threshold, thus
      alerting the surveillance team to the outbreak. On the date that the public
      health team were first notified of the outbreak our model predicted a 4% chance
      of detection when we assumed that one-twentieth of cryptosporidiosis cases
      telephoned the helpline. This rose to a 72% chance when we assumed nine-tenths of
      cases telephoned. The NHS Direct surveillance system is currently unlikely to
      detect an event similar to the cryptosporidiosis outbreak used here and may be
      most suited to detecting more widespread rises in syndromes in the community, as
      previously demonstrated. However, the expected rise in NHS Direct call rates,
      should improve early warning of outbreaks using call data.

PMID- 16409647
TI  - Contact rates and exposure to inter-species disease transmission in mountain
      ungulates.
AB  - The risk for a pathogen to cross the species barrier depends on the rate of
      efficient contacts between the species. However, contact rates between species
      have rarely been estimated from observations. Here we estimate contact rates and
      exposure of chamois Rupicapra rupicapra and Alpine ibex Capra ibex exposed to
      domestic pasteurellosis and brucellosis carried by sheep or cattle herds
      summering in mountain pastures. We use field observation data on animal positions
      treated in a geographic information system (GIS). Comparing 10 pastures, we show
      that the management of domestic herds influences the risk of inter-species
      transmission. Exposure to direct transmission of pasteurellosis is high when
      herds are not guarded nor enclosed, whereas exposure to indirect transmission of
      brucellosis is increased on epidemiological dangerous points such as salt
      deposits. Our preliminary results need further investigation, but they underline
      the importance of both herd management and pathogen transmission mode when the
      aim is to reduce the risk of contamination of wild populations by a pathogen
      associated with domestic pathogens.

PMID- 16409648
TI  - Investigating the potential spread of infectious diseases of sheep via
      agricultural shows in Great Britain.
AB  - The rate at which infectious diseases spread through farm animal populations
      depends both on individual disease characteristics and the opportunity for
      transmission via close contact. Data on the relationships affecting the contact
      structure of farm animal populations are, therefore, required to improve
      mathematical models for the spatial spread of farm animal diseases. This paper
      presents data on the contact network for agricultural shows in Great Britain,
      whereby a link between two shows occurs if they share common competitors in the
      sheep class. Using the network, the potential for disease spread through
      agricultural shows is investigated varying both the initial show infected and the
      infectious period of the disease. The analysis reveals a highly connected network
      such that diseases introduced early in the show season could present a risk to
      sheep at the majority of subsequent shows. This data emphasizes the importance of
      maintaining rigorous showground and farm-level bio-security.

PMID- 16409649
TI  - Hotspots: are some areas of sewer network prone to re-infestation by rats (
      Rattus norvegicus ) year after year?
AB  - The records of sewer baiting work for three London boroughs were examined to see
      whether there were locations that exhibited 'rat' (Rattus norvegicus) activity
      more often than would be expected by chance, a feature we dubbed 'hotspots'. More
      than 100000 baiting records were checked covering 15 years of the London Borough
      of Enfield (Enfield) and 5 years each of the London Borough of Barnet (Barnet),
      and the Royal Borough of Kensington and Chelsea (RBKC). The additional boroughs
      were included for comparison to see whether any effect observed was confined to
      Enfield or was a feature that could be found in both inner and outer city
      locations. Each borough was divided into kilometre squares corresponding with
      those found both on Ordnance Survey maps and also Thames Water Utilities Asset
      maps. The number of records per square were logged and then the number of
      positive records for all the manholes in that square on a year-on-year basis. We
      examined 350 km2 in Enfield, 377 km2 in Barnet and 66 km2 in RBKC. The data were
      subjected to a weighted analysis (i.e. allowing for the number of manholes per
      square and the varying total rat population from year to year). Some areas were
      shown to exhibit significantly higher amounts of activity than others suggesting
      that their distribution is not random and that there must be environmental and
      other factors, which make certain locations attractive to rats. Squares with very
      high activity, repeating year-on-year, 'hotspots', were found in all three
      boroughs, suggesting that the phenomena are widespread.

PMID- 16409650
TI  - Crohn's disease in people exposed to clinical cases of bovine paratuberculosis.
AB  - Mycobacterium avium subspecies paratuberculosis (Map), the cause of ruminant
      paratuberculosis, has been proposed as the causative agent of Crohn's disease.
      The objective of this study was to determine whether exposure to clinical cases
      of bovine paratuberculosis was a risk factor for Crohn's disease. A questionnaire
      was sent to dairy farmers living on premises where the occurrence or absence of
      clinical cases of bovine paratuberculosis had previously been determined. The
      prevalence of Crohn's disease was found to be similar to that reported in other
      studies in the United Kingdom and showed no association with bovine
      paratuberculosis. There was, however, a univariate association with geographical
      region. Ulcerative colitis showed univariate associations with age, frequency of
      contact with cattle and with smoking. The results do not support the hypothesis
      that Map plays a causative role in the aetiology of Crohn's disease.

PMID- 16409651
TI  - A high incidence of intussusception in Japan as studied in a sentinel hospital
      over a 25-year period (1978-2002).
AB  - The development of second-generation rotavirus vaccines requires knowledge of
      baseline incidence rates for intussusception in infants prior to vaccine
      introduction. To obtain such estimates we reviewed clinical records in a hospital
      that served as the major provider of paediatric beds in a local community in the
      northern part of Japan. During the 25-year period (1978-2002), there were 91
      hospitalizations due to radiologically confirmed intussusception in children <5
      years of age, of which 45% were <1 year of age. Assuming that all children with
      intussusception in the area had been admitted to this hospital, there were an
      average of 185 and 78 hospitalizations per 100000 person-years for children <1
      year old and 5 years old respectively. There was period-to-period variability
      with no long-term secular trend in the incidence of intussusception. The
      incidence rate in Japan was among the highest thus far reported, providing
      further evidence of geographic variability.

PMID- 16409653
TI  - Measles virus-specific antibody levels in Sudanese infants: a prospective study
      using filter-paper blood samples.
AB  - We conducted a prospective birth cohort study in rural Sudan to assess measles
      virus (MV)-specific antibody levels at different time points in infancy. Dried
      blood spots were collected on filter paper at birth (cord blood) and at ages 6,
      12 and 24 months (heel-prick). Maternally derived MV-specific antibody levels
      were high in cord blood samples, but at the age of 6 months had dropped below cut
      off values in half of the infants. By extrapolation it was concluded that the
      current Expanded Programme of Immunization (EPI) target age for measles
      vaccination of 9 months was an appropriate choice for this area. At the age of 24
      months acquired MV-specific antibodies were detected in 65-85% of the cohort,
      which corresponded well with the 79% of infants reported to be vaccinated by this
      age. This study demonstrates the usefulness of filter paper blood samples for
      seroepidemiological studies in developing countries.

PMID- 16409652
TI  - Repeated influenza vaccination of healthy children and adults: borrow now, pay
      later?
AB  - A growing number of publications are recommending annual influenza vaccination of
      healthy children and adults. However, the long-term consequences of repeated
      influenza vaccination are unknown. We used a simple model of recurrent influenza
      infection to assess the likely impact of various repeated influenza vaccination
      scenarios. The model was based on a Markovian framework and was fitted on annual
      incidence rates of influenza infection by age. We found that natural influenza
      infection reduced the risk of being re-infected by 15.4% (95% confidence interval
      7.1-23.0). Various scenarios of repeated influenza vaccination were then
      simulated and compared with a reference scenario where vaccination is given from
      age 65 years onwards. We show that repeated vaccination at a young age
      substantially increases the risk of influenza in older age, by a factor ranging
      between 1.2 (vaccination after 50 years) to 2.4 (vaccination from birth). These
      findings have important implications for influenza vaccination policies.

PMID- 16409654
TI  - Detection of hepatitis A virus from clotting factors implicated as a source of
      HAV infection among haemophilia patients in Korea.
AB  - To investigate the causal relationship of blood clotting factors and hepatitis A
      virus (HAV) infection in haemophilia patients during 1998-1999 in Korea, we
      performed a 1:3 matched case-control study and molecular detection of HAV from
      clotting factors and patients. The epidemiological investigation showed that one
      lot of clotting factor VIII was related epidemiologically to patients with
      hepatitis A with an odds ratio of 35.0, or 38.4 when adjusted for the interval
      between injections. We examined 17 sera collected from seven patients and 124
      lots of blood clotting factors (factor VIII and factor IV) by HAV reverse
      transcriptase-polymerase chain reaction (RT-PCR). HAV RNA was detected in five
      clotting factors and six sera. The HAV sequence of one of the factor VIII samples
      was identical to the sequences found in three patients' sera. Findings from the
      laboratory and epidemiological studies suggested that the clotting factor was
      causally related to HAV infection in three haemophilia patients.

PMID- 16409655
TI  - Seroprevalence of hepatitis E virus (HEV) antibody and the possible association
      with chronic liver disease: a case-control study in Albania.
AB  - A case-control study involving 109 in-patients with chronic liver disease and 190
      in-patients with no apparent liver disease was conducted to evaluate the
      seroprevalence of anti-HEV antibodies and the possible association with chronic
      liver disease. Among cases, the anti-HEV prevalence was 36.6% which increased
      significantly by age; among controls, the prevalence was 12.1% (P<0.05) and was
      similar among age groups <60 years. Among cases, aged >50 years (OR 4.0, 95% CI
      1.4-11) and the presence of end stage liver disease (ESLD) (OR 4.3, 95% CI 1.4
      12.8) were associated independently with anti-HEV positivity. The mean optical
      density, determined by anti-HEV immunoenzymatic test, was significantly higher
      among patients with ESLD, compared to the other patients. These results indicate
      that there is a high seroprevalence of anti-HEV in patients with chronic liver
      disease and a possible association between HEV infection and/or anti-HEV
      production and advanced stage chronic liver disease.

PMID- 16409657
TI  - Frequency of infectious gastrointestinal illness in Australia, 2002: regional,
      seasonal and demographic variation.
AB  - To estimate the frequency of infectious gastroenteritis across Australia, and to
      identify risk factors, we conducted a national telephone survey of 6087 randomly
      selected respondents in 2001-2002. The case definition was three or more loose
      stools and/or two or more vomits in a 24-hour period in the last 4 weeks, with
      adjustment to exclude non-infectious causes and symptoms secondary to a
      respiratory infection. Frequency data were weighted to the Australian population.
      Multivariate logistic regression was used to assess potential risk factors
      including season, region, demographic and socioeconomic status. Among contacted
      individuals, 67% responded. The case definition applied to 7% of respondents
      (450/6087) which extrapolates to 17.2 million (95% CI 14.5-19.9 million) cases of
      gastroenteritis in Australia in one year, or 0.92 (95% CI 0.77-1.06) cases/person
      per year. In the multivariate model, the odds of having gastroenteritis were
      increased in summer and in the warmest state, in young children, females, those
      with higher socioeconomic status and those without health insurance.

PMID- 16409656
TI  - Variations in case fatality and fatality risk factors of meningococcal disease in
      Western Norway, 1985-2002.
AB  - In a retrospective epidemiological study, 293 meningococcal disease patients
      hospitalized during 1985-2002, were examined for fatality and risk factors
      related to death. The overall case fatality rate (CFR) was 8.2%, but increased
      from 4% during 1985-1993 to 17% during 1994-2002. The latter 9-year period was
      characterized by more serogroup C infections and more patients with
      thrombocytopenia on admission to hospital. All patients categorized as meningitis
      on admission survived. Of the 24 patients who died, 21 had meningococcal skin
      rash on admission, 23 had an onset to admission time of < or =24 h, and 16 had
      severe septicaemia with hypotension and/or ecchymoses without meningitis on
      admission. By multivariate analyses, a short onset to admission time, >50
      petechiae, thrombocytopenia and severe septicaemia on admission were associated
      with fatality. More lives could be saved through earlier admission to hospital.
      This can be achieved through more information to the public about the early signs
      of meningococcal septicaemia, with the recommendation to look for skin rash in
      patients with acute fever during the first day and night.

PMID- 16409658
TI  - Temperature dependence of reported Campylobacter infection in England, 1989-1999.
AB  - Campylobacter is the most common bacterial cause of gastroenteritis in England
      and Wales, with 45000 cases reported annually. Campylobacter incidence is highly
      seasonal; the consistent peak in late spring suggests a role for meteorological
      factors in the epidemiology of this organism. We investigated the relationship
      between ambient temperature and Campylobacter enteritis using time-series
      analysis to study short-term associations between temperature and number of
      Campylobacter reports adjusted for longer-term trend and seasonal patterns. We
      found a linear relationship between mean weekly temperature and reported
      Campylobacter enteritis, with a 1 degrees C rise corresponding to a 5% increase
      in the number of reports up to a threshold of 14 degrees C. There was no
      relationship outside this temperature range. Our findings provide evidence that
      ambient temperature influences Campylobacter incidence, and suggest that its
      effect is likely to be indirect, acting through other intermediate pathways.

PMID- 16409659
TI  - Antimicrobial resistance in Campylobacter jejuni from humans and broilers in
      Norway.
AB  - In this study comprising isolates from 2001 to 2003, resistance was considerably
      more widespread among Campylobacter jejuni from humans infected abroad than
      infected within Norway. The discrepancy was particularly notable for
      fluoroquinolone resistance (67.4% vs. 6.5%). This is probably a reflection of a
      low resistance prevalence in Norwegian broiler isolates (1.2% fluoroquinolone
      resistant).

PMID- 16409660
TI  - Super-shedding cattle and the transmission dynamics of Escherichia coli O157.
AB  - The prevalence of Escherichia coli O157 displays striking variability across the
      Scottish cattle population. On 78% of farms, in a cross-sectional survey of 952,
      no shedding of E. coli O157 was detected, but on a small proportion,
      approximately 2%, very high prevalences of infection were found (with 90-100% of
      pats sampled being positive). We ask whether this variation arises from the
      inherent stochasticity in transmission dynamics or whether it is a signature of
      underlying heterogeneities in the cattle population. A novel approach is taken
      whereby the cross-sectional data are viewed as providing independent snapshots of
      a dynamic process. Using maximum-likelihood methods to fit time-dependent
      epidemiological models to the data we obtain estimates for the rates of
      immigration and transmission of E. coli O157 infection - parameters which have
      not been previously quantified in the literature. A comparison of alternative
      model fits reveals that the variation in the prevalence data is best explained
      when a proportion of the cattle are assumed to transmit infection at much higher
      levels than the rest - the so-called super-shedders. Analysis of a second
      dataset, comprising samples taken from 32 farms at monthly intervals over a
      period of 1 year, additionally yields an estimate for the rate of recovery from
      infection. The pattern of prevalence displayed in the second dataset also
      strongly supports the super-shedder hypothesis.

PMID- 16409661
TI  - Escherichia coli O157 outbreak associated with fresh unpasteurized goats' cheese.
AB  - A family cluster of three cases of Escherichia coli O157 infection was identified
      in France. Two cases developed haemolytic-uraemic syndrome. The source was fresh
      unpasteurized goats' cheese, produced by an independent producer. Three E. coli
      O157 strains, isolated from one HUS case and faeces of one cow and one goat, were
      indistinguishable by toxin type and PFGE pattern.

PMID- 16409662
TI  - An outbreak of Cryptosporidium hominis infection at an Illinois recreational
      waterpark.
AB  - Cryptosporidium has become increasingly recognized as a pathogen responsible for
      outbreaks of diarrhoeal illness in both immunocompetent and immunocompromised
      persons. In August 2001, an Illinois hospital reported a cryptosporidiosis
      cluster potentially linked to a local waterpark. There were 358 case-patients
      identified. We conducted community-based and waterpark-based case-control studies
      to examine potential sources of the outbreak. We collected stool specimens from
      ill persons and pool water samples for microscopy and molecular analysis.
      Laboratory-confirmed case-patients (n=77) were more likely to have attended the
      waterpark [odds ratio (OR) 16.0, 95% confidence interval (CI) 3.8-66.8], had pool
      water in the mouth (OR 6.0, 95% CI 1.3-26.8), and swallowed pool water (OR 4.5,
      95% CI 1.5-13.3) than age-matched controls. Cryptosporidium was found in stool
      specimens and pool water samples. The chlorine resistance of oocysts, frequent
      swimming exposures, high bather densities, heavy usage by diaper-aged children,
      and increased recognition and reporting of outbreaks are likely to have
      contributed to the increasing trend in number of swimming pool-associated
      outbreaks of cryptosporidiosis. Recommendations for disease prevention include
      alteration of pool design to separate toddler pool filtration systems from other
      pools. Implementation of education programmes could reduce the risk of faecal
      contamination and disease transmission.

PMID- 16409663
TI  - Comparing Shigella waterborne outbreaks in four different areas in Greece: common
      features and differences.
AB  - In Greece the public health surveillance for most infectious diseases, including
      shigellosis, is not well developed. However, four waterborne outbreaks of
      shigellosis have been recorded in Greece in the last three decades, in different
      areas of the country, under different environmental and socioeconomic conditions.
      This study presents the epidemiological characteristics of these four outbreaks
      in order to examine common points and differences and to investigate their
      possible association with environmental and socioeconomic conditions. All four
      outbreaks were caused by Shigella sonnei and related to drinking water. Epidemic
      curves, distribution of cases by age and gender, hospitalization rates,
      environmental conditions and laboratory results were compared. The outbreaks
      seemed to correspond to two different 'models' presenting two characteristic
      types of epidemic waves related to specific environmental conditions. The attack
      rates for the general population varied from about 9 to 13% and were similar for
      both sexes. Children were affected mostly. In these outbreaks there was a strong
      suspicion of contamination of the water distribution system from the sewage
      network, highlighting the importance of environmental health control measures.

PMID- 16409664
TI  - Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.
AB  - We evaluated the association between typhoid fever and Helicobacter pylori
      infection, as the latter microorganism may influence gastric acid secretion and
      consequently increase susceptibility to Salmonella typhi infection. Anti-H.
      pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were
      determined in the plasma of 87 blood culture-confirmed typhoid fever cases
      (collected after clinical recovery) and 232 random healthy controls without a
      history of typhoid fever, in the Jatinegara district, Jakarta. Patients with
      typhoid fever more often than controls were seropositive for H. pylori IgG (67%
      vs. 50%, P<0.008), when antibody titres were dichotomized around median titres
      observed in controls. H. pylori IgA seropositivity was not associated with
      typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e.
      gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid
      fever cases compared to controls (P=0.54 and P=0.27 respectively). In a
      multivariate analysis, typhoid fever was independently associated with young age
      (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence
      interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10
      3.40). Typhoid fever was independently associated with H. pylori IgG
      seropositivity, but not with elevated gastrin concentration. Therefore, the
      association suggests a common risk of environmental exposure to both bacteria,
      e.g. poor hygiene, rather than a causal relationship via reduced gastric acid
      production.

PMID- 16409665
TI  - Trends in antimicrobial resistance phenotypes in non-typhoid Salmonellae from
      human and poultry origins in France.
AB  - A total of 1873 strains from human origin and 4283 strains from non-human origin
      of Salmonella enterica serotypes Typhimurium, Enteritidis, Heidelberg, Hadar and
      Virchow, collected over three years 1993, 1997 and 2000, were examined in order
      to determine the rate of antimicrobial resistance to 12 antimicrobial drugs. The
      objective of the study was to describe and to compare the evolution of the main
      resistance types in human and non-human isolates, focusing on the poultry sector.
      The evolution and the rates of antimicrobial resistances for the five serotypes,
      with the exception of Virchow, were almost comparable in strains isolated from
      human and non-human sources over the period studied. The most striking result
      concerning single resistance was the spectacular increase of the resistance
      frequency to nalidixic acid for the strains belonging to serotypes Hadar and
      Virchow, especially in the poultry food sector (14% in 1993 vs. 72% in 2000 for
      Salmonella Virchow, 4% in 1993 vs. 70% in 2000 for Salmonella Hadar) and also in
      human isolates (24% in 1997 vs. 48% in 2000 for S. Virchow, 31% in 1997 vs. 78%
      in 2000 for S. Hadar). In addition to the classical resistance to ampicillin,
      streptomycin, sulphonamide, chloramphenicol and tetracycline (ASSuCT resistance
      type), which stabilized between 1997 and 2000, the emergence of a new resistance
      type was observed.

PMID- 16409666
TI  - Epidemiological characteristics of Salmonella Typhimurium isolated from animals
      and feed in Poland.
AB  - Fifty-seven Salmonella Typhimurium strains isolated from poultry, swine and
      animal feed in Poland during the years 1979-1998 and 2000-2002 were analysed with
      conventional and molecular techniques. Antimicrobial resistance as well as
      multiresistance was found, respectively, in 80.1% and 56.1% of the isolates and
      most frequently among isolates from 2000-2002. Of several phage types noted,
      DT104 was prevalent among poultry, swine and feed isolates. DT104, U302 and non
      typable strains had a multiple resistant profile (ACSSuT) due to the presence of
      class I integrons. Pulse-field gel electrophoresis of XbaI and BlnI digest showed
      high genomic similarity between the strains and confirmed clonal spread of S.
      Typhimurium infections. Plasmid profiling allowed further differentiation of the
      strains. We have, therefore, confirmed the appearance of S. Typhimurium DT104
      showing genome integrated integron-mediated antimicrobial resistance in Poland.
      These findings are significant for public and animal health risks and document
      the dissemination of DT104 epidemic strains into new geographical regions.

PMID- 16409667
TI  - Molecular epidemiology and diversity of Salmonella serovar Typhimurium in pigs
      using phenotypic and genotypic approaches.
AB  - For epidemiological investigations of the most common and non-host-adapted
      Salmonella serotypes, such as Typhimurium, highly discriminatory approaches are
      essential. In the present study, we evaluated three genotyping methods; amplified
      fragment length polymorphism (AFLP), pulsed-field gel electrophoresis (PFGE) and
      repetitive palindromic extragenic-PCR (Rep-PCR) using 40 isolates. AFLP showed
      the highest discriminatory index (0.939), resolution and throughput. To determine
      clonality of Salmonella Typhimurium isolates and epidemiological relatedness in
      different commercial pig production units, we employed AFLP in combination with
      antimicrobial resistance pattern and phage typing. Salmonella serovar Typhimurium
      isolates (n=196) obtained from a longitudinal study of 18 pig farms over a 3-year
      period were studied. Using this approach, 16 distinct clonal types were
      identified. We found two common multidrug- resistant patterns including
      AmCmStSuTe and AmKmStSuTe. Two commonly multidrug- resistant phage types that are
      of known public health importance, DT104 and DT193, were also common. AFLP
      differentiated distinct clones within DT104, a phage type previously reported to
      be clonal. Fourteen of the clonal types were unique to one of the two production
      systems, showing diversity between independent commercial pig production systems
      located in the same geographical area. Clonal types obtained from nursery farms
      and corresponding finishing units were, however, similar.

PMID- 16409669
TI  - The medial amygdala controls the coital access of female rats: a possible
      involvement of emotional responsiveness.
AB  - Partner preference and paced mating tests were accomplished in ovariectomized
      female rats following bilateral radiofrequency lesions in the medial amygdala.
      Open field behavior and passive avoidance learning were also examined to
      investigate the underlying behavioral mechanism. Partner preference was
      determined in a chamber located between castrated and sexually active males.
      Airborne olfactory cues were presented to the female through small holes on the
      partition. The lesion diminished preference for the odor of sexually active males
      over that of castrated males, even after injection with a high-dose of estrogen.
      On the other hand, in a paced mating test the lesioned females without estrogen
      treatment showed a significantly shorter latency for entering the male's
      compartment in a two-compartment apparatus, which allowed the females, but not
      the males, to cross the barrier through a narrow opening at the bottom. However,
      an administration of estrogen and progesterone reduced the effect. The lesion had
      no effect on emotionality or exploratory behavior in an open field test, but it
      impaired passive avoidance learning capability. We suggest that a male poses an
      inherent threat to a female. The seemingly incompatible results of partner
      preference and paced mating tests can be compromised if the male is inherently
      aversive to the female; this emotional response can be removed by the medial
      amygdala lesion.

PMID- 16409668
TI  - Experimental airborne transmission of Salmonella Agona and Salmonella Typhimurium
      in weaned pigs.
AB  - This study tested the hypothesis of airborne transmission of Salmonella Agona
      (Trial I) and Salmonella Typhimurium (Trial II) in weaned pigs. The trials were
      performed using stainless-steel/glass isolation cabinets connected by air ducts
      to permit an unidirectional airflow from cabinet 1 (two control pigs) to cabinet
      3 (two sentinel pigs), passing through cabinet 2 (two inoculated pigs). Air
      samples, pooled faecal samples from the floor and rectal swabs were collected
      daily and assessed by culture and PCR. A fumigation chamber and rubber gloves
      coupled to the cabinets allowed sampling without opening the system. Trials I and
      II lasted 15 and 19 days respectively. The recovery of S. Agona and S.
      Typhimurium and detection of seroconversion in sentinel pigs indicate that
      airborne Salmonella transmission in weaned pigs over short distances is possible.
      Further studies on the role of aerosols in the epidemiology of Salmonella in
      intensive pig production should be performed.

PMID- 16409670
TI  - Recommendations for the management of premature ejaculation: BASHH Special
      Interest Group for Sexual Dysfunction.
AB  - We present the British Association for Sexual Health and HIV (BASHH), Special
      Interest Group for Sexual Dysfunction updated recommendations for the management
      of premature ejaculation. The recommendations outline the physiology, prevalence,
      definitions, aetiological factors and patient assessment for this common sexual
      problem. Behavioural, local and systemic pharmacological treatments are discussed
      along with general recommendations and auditable outcomes.

PMID- 16409671
TI  - Recommendations for the management of retarded ejaculation: BASHH Special
      Interest Group for Sexual Dysfunction.
AB  - We present the British Association of Sexual Health and HIV (BASHH) special
      interest group in sexual dysfunction recommendations for the management of
      retarded ejaculation. The recommendations outline the physiology, prevalence,
      definitions, aetiological factors and patient assessment for this sexual problem.
      We suggest treatment strategies, recommendations for management and an auditable
      outcome.

PMID- 16409672
TI  - Recommendations for the management of vaginismus: BASHH Special Interest Group
      for Sexual Dysfunction.
AB  - We present the British Association for Sexual Health and HIV (BASHH) Special
      Interest Group for Sexual Dysfunction recommendations for the management of
      vaginismus. The recommendations outline the history, prevalence, aetiological
      factors, patient assessment and management for this sexual problem. Treatment
      strategies are discussed along with general recommendations and auditable
      outcomes.

PMID- 16409673
TI  - Multicentric Castleman's disease in HIV infection.
AB  - Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder.
      The precise incidence is unknown, although it is more common in HIV-positive than
      HIV-negative individuals. The pathological features of MCD strongly suggest a
      chronic antigen stimulation response, and human herpes virus 8 (HHV8) has been
      found to be universal in cases of HIV-related MCD. The presentation is non
      specific with a wide differential diagnosis, which often results in a significant
      delay in its diagnosis. Diagnosis is made on the clinical presentation of a
      lymphoproliferative disorder, with evidence of multisystem involvement with
      classical histopathology on lymph node biopsy. Although no standard of care has
      been established for its treatment, symptomatic recurrences are often treated
      with corticosteroids and chemotherapy. The contribution of highly active
      antiretroviral treatment to the treatment of MCD remains debated. Novel
      treatments targeted at HHV8 show promising results, although evidence is
      currently limited to case reports. Randomized control trials assessing whether
      'prophylactic' treatment with ganciclovir may prevent flares as currently used
      against cytomegalovirus disease in transplant patients are proposed. The
      prognosis of MCD in HIV-positive patients remains generally poor with a median
      survival of 48 months from diagnosis, and a 15-fold increased risk of non
      Hodgkin's lymphoma.

PMID- 16409675
TI  - Chaperoning in genitourinary medicine clinics.

PMID- 16409676
TI  - Emergence of quinolone-resistant Neisseria gonorrhoeae in Pakistan.
AB  - Quinolone-resistant Neisseria gonorrhoeae (QRNG) have not been reported from
      Pakistan to date. This is the first report of the presence of QRNG in Pakistan.
      The study was performed at a tertiary care hospital laboratory in Karachi,
      Pakistan. Antimicrobial susceptibility data on all N. gonorrhoeae isolated
      between 1992 and 2002 were retrieved and analysed. Minimum inhibitory
      concentrations (MICs) of QRNG isolated in year 2002 were performed, and clinical
      information was collected. QRNG was first noted in 1999 and its proportion
      increased to 42% in 2002. MICs of the 12 isolates tested in 2002 showed a high
      level of resistance to ofloxacin with MIC of more than 4 microg/mL. Clinical
      information from patients with QRNG showed treatment failure. Emergence of QRNG
      in developing countries is alarming as there is no proper surveillance of
      increase in resistance. We strongly urge the need of detection and documentation
      of the resistant gonococcal isolates, as in vitro resistance is associated with
      clinical failure.

PMID- 16409677
TI  - Genital infection in male partners of women with chlamydial infection.
AB  - The aim of the present study was to examine the prevalence of infection among
      male contacts of women with endocervical chlamydiae. The study population
      consisted of men who attended the Department of Genitourinary Medicine at
      Edinburgh Royal Infirmary as named contacts of women with endocervical
      chlamydiae. The diagnosis of Chlamydia trachomatis was based on a polymerase
      chain reaction. Of 632 male contacts of 404 infected women, 155 (24%) attended
      the clinic, and 147 had satisfactory tests for chlamydiae; 64 (44%) men had
      chlamydial infection. A greater proportion of symptomatic men (14/22) were
      infected compared with asymptomatic men (50/125) (P<0.02). Symptomatic men
      attended the department earlier (median 0.0 days) than asymptomatic male contacts
      (median 11 days) (P<0.05). A greater proportion of male contacts of women with
      one partner (105/254) attended the clinic than those of women with two or more
      partners (42/112). Better counselling policies for chlamydial infection are
      needed to ensure improved rate of diagnosis and treatment of male contacts.

PMID- 16409678
TI  - The crisis in sexual health and developing genitourinary medicine services:
      lessons from a primary care trust.
AB  - The House of Commons Health Select Committee recently described a national crisis
      in sexual health. Alarmed by dramatic increases in the rates of sexually
      transmitted infections (STIs) and appalled by over-stretched, under-resourced
      genitourinary (GU) medicine services, the committee has called for urgent action.
      The increasing rates of STIs locally, a significant cluster of syphilis cases,
      and an over-burdened GU medicine service prompted Walsall primary care trust to
      undertake an evaluation of local service provision. The results were used to
      inform the development of GU medicine services locally and Walsall's sexual
      health strategy. This paper reports the results of the evaluation and the
      implications for service development. The Walsall GU medicine service was
      evaluated using three approaches, based on standards for GU medicine service
      provision identified from the literature. Routine data were used to analyse
      trends in STIs and service activity, including access times. These data further
      informed the evaluation process. Local stakeholder views on GU medicine service
      provision were sought using semi-structured interviews. Most standards relating
      to the provision of core services, including those for the management of patients
      with HIV infection, were met. High levels of patient satisfaction were reported.
      However, under-staffing, inadequate clinic facilities, and limited joint working
      with other agencies were highlighted as key concerns. Tackling sexual health
      inequalities and improving the sexual health of the population requires
      investment in resources and manpower, improved partnership working, and
      configuring services around the needs of patients. In addition, and perhaps most
      importantly, it will require a shift in how both health professionals and the
      public perceive and utilize sexual health services.

PMID- 16409679
TI  - Virological, serological and epidemiological study of 255 consecutive cases of
      genital herpes in a sexually transmitted disease clinic of Paris (France): a
      prospective study.
AB  - Some studies (mostly retrospective) have pointed to an increasing frequency (up
      to 60%) of herpes simplex virus type 1 (HSV-1) in genital herpes (GH), but they
      were biased towards severe or atypical cases. We wished to evaluate the frequency
      of HSV-1 in patients attending our clinic for both first and recurrent episodes
      of GH. All patients (men and women) with genital lesions compatible with GH were
      included in a prospective study between May 1999 and April 2002. For all patients
      a standardized questionnaire, clinical examination, MRC5 culture (Dade Behring),
      polymerase chain reaction (PCR)-herpes consensus (Argene Biosoft) in case of
      negative culture and type-specific herpes serology HSV-1 and HSV-2 (Elisa
      Eurobio) were obtained. Predictive factors associated with HSV-1 and HSV-2 GH
      were studied by uni- and multivariable analyses. In all, 255 patients had a
      positive culture (n = 216) or PCR (n = 39). A total of 248 patients had typable
      herpes (148 men and 100 women). Median age was 33 (27-43); 20% had anal herpes;
      48% had clinically recurrent lesions; 21% were HIV +; 20% of men were homosexual;
      77% practised oral sex. In all, 36 were HSV-1 (14.5%): more in women, 25/100
      (25%), than in men, 11/148 (7.5%) (odds ratio [OR]: 4 [1.8-9.1], P = 0.008). HSV
      1 accounted for 23% of cases of first clinical episodes (women: 31.5%; men:
      14.7%) (P = 0.02) and 6% of clinically recurrent episodes (women: 15%; men: 1.2%)
      (OR: 3.8 [1.6-9.1], P = 0.0033). Serological study was done in 239: primary
      infection was disclosed in 33 (HSV-1: 61%), HSV-2 non-primary first episode in 22
      and recurrence in 184 (HSV-1: 8%). In all, 37% of recurrent episodes presented as
      a first clinical episode. HSV-1 was linked in men with homosexuality (P<0.01) and
      anilingus (P<0.01), in women with younger age (P<0.01), more sexual intercourses
      (P<0.0001) and more oral sex (P<0.001). Although HSV-1 is frequent in first
      clinical (23%) and primary (61%) episodes of GH, recurrent GH remains mostly due
      to HSV-2 (94%).

PMID- 16409680
TI  - HIV risk behaviour patterns, predictors, and sexually transmitted disease
      prevalence in the social networks of young men who have sex with men in St
      Petersburg, Russia.
AB  - HIV seroconversions and sexually transmitted diseases (STDs) are often clustered
      in social networks within community populations. The present study was carried
      out among men who have sex with men in Russia, where a major HIV epidemic is
      unfolding, and where social networks have played a historically important role.
      In all, 38 social networks were recruited into the study, and members of all
      networks (n = 187) completed risk behaviour assessments and were tested for STDs.
      About 17% of participants had STDs, and 10% of men had syphilis. Over 64% of men
      had recent unprotected anal intercourse (UAI), including 51% who did so with main
      partners, 30% who did so with casual partners, and 32% who had UAI with multiple
      male partners. The strongest predictor of all risk behaviour indicators and STDs
      was the social network, to which an individual belonged, supplemented by peer
      norm perceptions and intentions to practise safer sex. There was a high level of
      correspondence in behaviour between the social leader of a network and its other
      members. Social networks should be directly targeted in HIV prevention efforts.

PMID- 16409681
TI  - Decrease of human immunodeficiency virus prevalence in antenatal clinics in
      Abidjan, Cote d'Ivoire, 1995-2002.
AB  - Antenatal HIV seroprevalence surveys are important tools to understand the extent
      of the HIV epidemic in Africa. The main objective is to describe HIV prevalence
      trends from 1995-2002 in pregnant women consulting antenatal clinics in Abidjan,
      Cote d'Ivoire. We proposed HIV test to pregnant women consulting antenatal
      clinics in Abidjan from 1995-2002 in a programme of prevention of mother-to-child
      transmission of HIV. Yearly prevalence was estimated. Overall, 36,442 women were
      tested. Prevalence decreased from 14-15% in 1995-96 to 11% in 2002. The
      prevalence among 18-22-year-old women dropped from 15% in 1995 to 8% in 2002,
      while for older women it increased slightly, or remained stable from 1995-1999
      and decreased thereafter. HIV prevalence among women consulting antenatal clinics
      has been decreasing overall. This is the first such report among pregnant women
      in Abidjan, probably the result of different phenomena: ageing of the epidemic
      and behaviour changes (disease awareness and prevention campaigns).

PMID- 16409682
TI  - Serum creatine phosphokinase monitoring in patients infected with HIV.
AB  - Creatine phosphokinase (CPK) estimations are done routinely in some HIV clinics,
      irrespective of patient symptoms. We studied patients attending the
      Worcestershire HIV clinic between 1987 and 2001 to identify whether routine
      elevations in serum levels of CPK in patients with HIV were associated with
      clinical features of muscle disease (CFMD), and whether such elevations
      influenced patient management. There was no association between CFMD and a rise
      in CPK. Major rises of CPK >400 IU/L were significantly associated with CFMD. No
      individual had a persistent CPK rise >200 IU/L without CFMD. In the great
      majority of cases, there was no change in management consequent to enzyme rises.
      In patients with HIV infection and no CFMD, the chance of finding a major and
      persistent CPK rise is low. This study does not support the practice of routine
      monitoring of CPK in asymptomatic patients attending HIV clinics.

PMID- 16409683
TI  - Multicentric Castleman's disease in a patient with HIV.
AB  - Multicentric Castleman's disease (MCD) was originally described in non-HIV
      patients. It is a rare lymphoproliferative disorder, which is more commonly seen
      in HIV-positive patients and is associated with human herpes virus-8 (HHV-8). We
      describe a patient with advanced HIV who responded well to conventional highly
      active antiretroviral treatment. She was diagnosed with MCD soon after her
      diagnosis of HIV. She presented with multiple flares of her MCD. The case
      illustrates the difficulty of differentiating between episodes of septicaemia and
      a flare of MCD. The patient was treated with various chemotherapy regimens, which
      included several cycles of liposomal doxyrubicin and etoposide. There is
      currently no consensus on the treatment of MCD and various therapies are
      described in the literature, which include chemotherapy. Chemotherapy must be
      chosen with the immunosuppressive effects of the treatment being considered with
      caution. Both doxyrubicin and etoposide are well tolerated and successfully
      controlled the symptoms of MCD in our patient.

PMID- 16409684
TI  - Saxophone penis revisited.
AB  - Saxophone deformity of the penis is commonly secondary to diseases causing
      chronic lymphatic obstruction. Lymphogranuloma venereum (LGV) is an important
      cause for this deformity. A case of LGV in genito-anorectal syndrome with a
      saxophone penis is reported along with the contrast-enhanced computed tomography
      (CECT) findings of anorectal involvement, and a probable hypothesis for this
      typical appearance of the penis.

PMID- 16409685
TI  - Reactivation of latent hepatitis B virus infection with HIV-related
      immunosuppression.
AB  - The effect of HIV-related immunosuppression and antiretroviral therapy on the
      reactivation of latent hepatitis B virus (HBV) infection is unclear. We report
      four patients with advanced HIV-related immunosuppression and abnormal liver
      function tests who had evidence of HBV reactivation. Reclearance of hepatitis B
      occurred in two cases with HIV treatment regimens not containing lamivudine,
      suggesting that improved immune function may be responsible. In three cases, HBV
      reactivation was recognized during investigation for abnormal liver function
      initially attributed to drug toxicity. The possibility of HBV reactivation must
      be considered in the differential diagnosis of abnormal liver function in cases
      with advanced HIV.

PMID- 16409686
TI  - Penile Mondor's disease and inherited thrombophilia.

PMID- 16409687
TI  - Impact of modernizing medical careers on GU medicine.

PMID- 16409688
TI  - Introduction of a proforma in the management of under-age attendees at a
      genitourinary clinic.

PMID- 16409689
TI  - Kaposi's sarcoma-associated immune reconstitution following highly active
      antiretroviral treatment initiation.

PMID- 16409690
TI  - Professor Takahide Mori.

PMID- 16409691
TI  - Italian law on assisted conception: clinical and research implications.
AB  - The Italian law 40/2004 regulating the use of assisted conception will remain on
      the statutes after the failure of the referendum in June 2005. Italy is now one
      of the most restrictive countries in the world in the field of assisted
      conception. It is thought that the new regulations, which have already increased
      'reproductive tourism' in Italian subfertile couples, will also have clinical and
      research implications.

PMID- 16409693
TI  - Recombinant gonadotrophins in reproductive medicine: gold standard for ovarian
      stimulation therapy in the 21st century.
AB  - The clinical use of gonadotrophin preparations started in the 1960s when it was
      possible to extract human menopausal gonadotrophins from urine of post-menopausal
      women. Recombinant gonadotrophins became available in 1995. Whereas in other
      therapeutic areas the introduction of pure, recombinant preparations such as
      insulin and growth hormone has lead to rapid phasing out of biological extraction
      based therapies, this is different for gonadotrophins. It is difficult to
      understand why even today women are exposed to urinary products although the
      benefits of recombinant gonadotropohins in terms of safety are obvious.

PMID- 16409694
TI  - Recombinant follicle-stimulating hormone: gold standard or not?
AB  - Recombinant follicle stimulating hormone has been available now for almost 10
      years and many couples have benefited from its use. Its clinical efficacy, purity
      and safety profile have been extensively documented in numerous publications.
      Because of growing public concerns on the safety of gonadotrophins extracted from
      human urine, the future will lie in the recombinant technology, which will also
      enable the design of more convenient tailor-made gonadotrophins.

PMID- 16409695
TI  - Are recombinant gonadotrophins safer, purer and more effective than urinary
      gonadotrophins?
AB  - Recombinant gonadotrophins have been proposed as the gold standard for current
      infertility treatment. However, there is little difference between the various
      available urinary or recombinant gonadotrophins in terms of safety, purity or
      clinical efficacy. Resources committed to determining an advantage of one
      gonadotrophin preparation over another would be better spent on research for new
      treatments.

PMID- 16409696
TI  - Respective efficacy of gonadotrophins should be the heart of the debate.
AB  - Recombinant gonadotrophins offer future advances in reproductive medicine. It is
      questionable whether they produce more pregnancies than urinary gonadotrophins.
      No doubt future advances will permit this goal, but this has not yet been
      attained.

PMID- 16409697
TI  - Recombinant or urinary gonadotrophins - an Australian perspective.
AB  - The Australian experience of gonadotrophin stimulation is a useful example of
      steps that lead to a country deciding to use recombinant FSH solely.

PMID- 16409698
TI  - Recombinant gonadotrophins in reproductive medicine: a viewpoint from India.

PMID- 16409699
TI  - Cost restricts the value of recombinant FSH.

PMID- 16409700
TI  - The embryologist as counsellor during assisted reproduction procedures.
AB  - This study aimed to establish whether patients who receive support counselling by
      the embryologist as counsellor during assisted reproduction procedures would be
      better equipped with efficient coping mechanisms than patients who were not
      counselled. Sixty patients were randomly assigned to either the support
      counselling or the control groups. Questionnaires, measuring pre- and post
      treatment levels of anxiety, depression and ways of coping, were presented to
      both groups. The support counselling group received emotional support and
      counselling from the embryologist. The control group were treated routinely,
      received no counselling or emotional support and were asked to phone the
      gynaecologist daily concerning embryo development. Despite reliable internal
      consistency, the hypothesis was not accepted due to non-significant differences
      between the groups. However, t-tests indicated a changed pattern of behaviour
      within the support counselling group, who experienced a statistically significant
      (P < 0.017) reduction in anxiety levels after the counselling intervention, as
      well as increased use of problem-focused coping strategies, such as instrumental
      action, in dealing with the demands of the treatment programme.

PMID- 16409701
TI  - Ethical issues in paying for long-distance travel and accommodation expenses of
      oocyte donors.
AB  - In many countries where the sale and purchase of donor oocytes is banned, a legal
      loophole often exploited is the use of free air tickets and hotel stay to entice
      prospective oocyte donors, in lieu of monetary payment. Such a means of procuring
      much-needed donor oocytes is ethically unsound. There is a lack of transparency
      and the personal motivation of the oocyte donor may be clouded by the desire for
      a 'free' holiday. Moreover, such a system is open to abuse by medical
      professionals. Private fertility clinics may source for oocyte donors to attract
      patients. The oocyte donor is paid nothing (except free travel and hotel stay),
      while the medical professional makes a handsome profit from treating infertile
      patients, which is not equitable. Medical professionals can also easily make a
      profit by marking up the price of air tickets and hotel stay to the patient
      (oocyte recipient). This would be thoroughly unprofessional, since the money
      earned is not directly related to the medical skills and expertise of the
      fertility specialist. Hence, it is imperative that various regulatory authorities
      should critically re-examine the giving of free travel and accommodation to
      oocyte donors, instead of monetary compensation.

PMID- 16409703
TI  - FSH: what is the highest dose for ovarian stimulation that makes sense on an
      evidence-based level?
AB  - The widely applied practice of a gonadotrophin dose increase in case of low
      response is not on an evidence-based level and not efficacious. All known
      comparative studies failed to show a difference in favour of the high-dose group
      regarding their pregnancy rate per embryo transfer. However if more oocytes and
      more embryos are available for cryopreservation, the real benefit in terms of
      cumulative pregnancy outcome might be with the high-dose regimen. This
      publication will show - as a review of the literature - that the frequent
      clinical practice of increasing the FSH dose does not lead to a higher pregnancy
      rate, which is in line with recommendation for milder stimulation regimes in IVF.
      Thus, the collective evidence to date would suggest that 150 IU/day to 250 IU/day
      of FSH or human menopausal gonadotrophin (HMG) is an appropriate starting dose
      for most women undergoing ovarian hyperstimulation for IVF as part of a
      gonadotrophin-releasing hormone (GnRH) antagonist or a long GnRH agonist
      protocol.

PMID- 16409706
TI  - Impact of androgens on fertility - physiological, clinical and therapeutic
      aspects.
AB  - Ovarian androgen synthesis and regulation are essential to ensure adequate
      steroidogenesis and folliculogenesis. In primates, there is evidence for a direct
      impact on the number of small antral follicles and on the process of chronic
      anovulation. Therefore, serum androgen should be more carefully assessed in
      infertile women. Accurate measurements of serum androgen are required to better
      identify patients with androgen excess or deficiency. Medical or surgical
      interventions are able to decrease ovarian androgen excess and to reduce the risk
      of hyperstimulation. Conversely, androgen supplementation should be considered in
      women at risk of low ovarian response to gonadotrophins, related to androgen
      deficiency. This review supports a specific and broad role of androgen in
      reproductive physiology.

PMID- 16409704
TI  - Factors influencing response to ovarian stimulation.
AB  - Ovarian stimulation is an integral part of assisted reproduction treatments.
      Ovarian response to gonadotrophin treatment, besides other factors, determines
      the outcome of treatment, as the number and quality of oocytes retrieved are
      related to the chance of achieving a pregnancy. A number of factors have been
      identified that might predict ovarian response, such as age of the patient and
      antral follicle count. In addition, it has been shown that genetic factors such
      as the patient's FSH-receptor genotype also determine individual response to FSH
      treatment. Besides patient-related factors, the choice of drugs for ovarian
      stimulation plays a significant role. Until recently, biopotency of gonadotrophin
      preparations was tested by an in-vivo bioassay with an intrinsic variability up
      to 20%. Due to a superior manufacturing technique, follitropin alpha can now be
      filled by mass. This allows assessment of FSH with a precise SE-HPLC assay and
      variability of the FSH content between production lots has now been estimated at
      1.6%. Results of recent studies indicate that treatment with follitropin alpha
      filled by mass results in consistent ovarian response, fewer treatment days and
      fewer cancelled cycles. This is an important step towards further minimizing drug
      related variability of ovarian response to FSH treatment.

PMID- 16409707
TI  - Hyperprolactinaemia and the regular menstrual cycle in asymptomatic women: should
      it be treated during therapy for infertility?
AB  - It is known that hyperprolactinaemia can cause galactorrhoea and irregular cycles
      or even amenorrhoea. High serum prolactin (PRL) can disturb follicular maturation
      and corpus luteum function. Treatment of hyperprolactinaemia in patients with
      resulting bleeding anomalies is established, but the question is how to manage
      normal cyclic hyperprolactinaemic women? Studies have shown that in a subgroup of
      asymptomatic patients the serum contains mainly high molecular weight form (big
      big PRL), which has a low bioactivity, called macroprolactinaemia. It is evident
      that macroprolactin does not affect the control of pituitary PRL secretion via
      the short loop feedback mechanism or the secretion of gonadotrophins as does
      monomeric PRL. Identification of macroprolactinaemia is therefore clinically
      important to prevent unnecessary examinations and inappropriate treatment.
      Prolactinoma can be associated with macroprolactinaemia. Performance of pituitary
      imaging in asymptomatic patients with hyperprolactinaemia may therefore be
      justified, but further studies are needed to evaluate the relation of costs and
      benefit. An unsolved problem is the differentiation between inactive and PRL
      secreting tumours. Caution should be exercised concerning medical treatment in
      unstimulated patients and also in patients during ovarian stimulation alone or in
      combination with intrauterine insemination or in-vitro fertilization. The
      potential clinical significance of hyperprolactinaemia/macroprolactinaemia in
      asymptomatic women must be further evaluated.

PMID- 16409708
TI  - Pharmacogenetics in ovarian stimulation - current concepts and future options.
AB  - Tailoring ovarian stimulation to the individual patient can be challenging
      because the ovarian response varies substantially between patients.
      Pharmacogenetics has emerged as a new area of research to improve the balance
      between desired and undesired actions of drugs, based upon the genetic
      predisposition of the individual patient. Clinical studies have demonstrated that
      the p.N680S polymorphism of the FSH-receptor gene determines the ovarian response
      to FSH stimulation in patients undergoing IVF. In homozygous Ser(680)/Ser(680)
      type women, the FSH receptor appears to be more resistant to FSH action even in
      normal menstrual cycles. Therefore, genotyping of patients scheduled for ovarian
      stimulation could be an attractive tool to individualize FSH dosing according to
      genetic differences in ovarian sensitivity. More clinical studies are warranted
      to investigate the usefulness of genotyping for the p.N680S polymorphism as a
      routine diagnostic test before ovarian stimulation.

PMID- 16409710
TI  - Cryosystem assessment by glucose uptake of murine blastocysts.
AB  - Glucose uptake was used as a measure of metabolic activity and implantation
      potential to compare vitrification and slow freezing in a prospective randomized
      trial using murine blastocysts. Frozen 2-cell embryos (n = 132) thawed and
      cultured for 48 h to the blastocyst stage were randomly divided into four groups:
      (i) control - not refrozen; (ii) slow freezing using a programmed rate (PR);
      (iii) vitrification by super-cooled (VSC) liquid nitrogen; and (iv) vitrification
      in liquid nitrogen (VLN). Upon re-thawing, embryos were cultured individually for
      24 h to determine glucose uptake non-invasively. Morphological assessments
      included total cell counts and inner cell mass (ICM) detection following
      immunosurgery. Mean glucose uptake was lower for each treatment (PR and VSC, 4.3
      pmol/embryo per h; VLN, 4.9 pmol/embryo per h) versus controls (6.8 pmol/embryo
      per h). PR and VSC embryos had fewer cells (57.4 +/- 24.2 and 64.1 +/- 31.5)
      versus controls (85.7 +/- 26.2), and fewer embryos containing a detectable ICM
      (42.9 and 61.8%) compared with controls (88.2%). The only difference between
      control and VLN embryos was absolute glucose uptake, although in both treatments
      glucose uptake was increased from embryos with an ICM compared with those
      without. Glucose uptake appears to be a sensitive, non-invasive method to
      validate cryopreservation protocols.

PMID- 16409712
TI  - Comparison of open and closed methods for vitrification of human embryos and the
      elimination of potential contamination.
AB  - Survival and development of human embryos was compared following slow cooling
      versus vitrification involving more than 13,000 vitrified embryos. In addition,
      the efficacy of an open system, the Cryotop, and a closed vitrification system,
      the CryoTip(trade mark), were compared using human blastocysts. One hundred
      percent of vitrified human pronuclear stage embryos survived and 52% developed to
      blastocysts as compared with 89% survival and 41% blastocyst development after
      slow cooling. Similar survival rates were seen with vitrification of 4-cell
      embryos (98%) as compared with slow cooling (91%). Furthermore, 90% of vitrified
      blastocysts survived and resulted in a 53% pregnancy rate following transfer, as
      compared with 84% survival and 51% pregnancy rates following slow cooling. All
      corresponding values were significantly different. When the closed and open
      vitrification systems were compared, no difference was found with regard to
      supporting blastocyst survival (93 and 97% for CryoTip and Cryotop respectively),
      pregnancies (51 versus 59% respectively) and deliveries (48 versus 51%
      respectively). Vitrification is a simple, efficient and cost-effective way to
      improve cumulative pregnancy rates per cycle. The use of the closed CryoTip
      system eliminates the potential for embryo contamination during cryopreservation
      and storage without compromising survival and developmental rates in vitro and in
      vivo.

PMID- 16409713
TI  - Effects of peritoneal fluid on preimplantation mouse embryo development and
      apoptosis in vitro.
AB  - To evaluate the effect of peritoneal fluid (PF) on preimplantation mouse embryo
      development and apoptosis, PF was obtained from women presenting with (n = 7) and
      without endometriosis (n = 7). Mouse embryos were cultured to the blastocyst
      stage in human tubal fluid medium alone (control) or 10% PF. Embryo development
      was assessed and the total cell number per embryo was determined by Hoechst 33258
      staining. Allocation of inner cell mass and trophectoderm in blastocysts, and
      incidence of apoptosis were determined using confocal microscopy. The blastocyst
      development rate was significantly lower in the presence of 10% PF (P < 0.01).
      Total cell number and trophectoderm in blastocysts cultured in culture media
      alone was significantly higher than in the presence of PF (P = 0.034 and P = 0.01
      respectively). A higher incidence of apoptosis was seen in blastocysts cultured
      in culture media alone, compared with those cultured in the presence of PF (P =
      0.04). PF decreases the development of early mouse embryos to the blastocyst
      stage, as well as the incidence of apoptosis in the resulting mouse blastocysts.
      No difference was seen in the effect of PF from women with and without
      endometriosis on mouse embryo development and apoptosis.

PMID- 16409714
TI  - Successful pregnancy following transfer of embryos from oocytes with abnormal
      zona pellucida and cytoplasm morphology.
AB  - The failed or impaired fertilization in an IVF cycle may be a result of
      undetected abnormalities in sperm function, poor oocyte quality, or impaired
      spermatozoon-oocyte interaction. Whether oocyte dysmorphisms have an impact on
      intracytoplasmic sperm injection (ICSI) outcome, fertilization, and implantation
      is controversial. A 33-year-old nulligravida female with a 2-year history of
      primary infertility was referred to the Toronto Centre for Advanced Reproductive
      Technology for infertility management. The patient underwent several cycles of
      ovulation induction followed by timed intercourse or intrauterine insemination
      without a resulting pregnancy. Following the failed insemination cycles, she
      proceeded to IVF. Six morphologically abnormal oocytes (including three that were
      cucumber-shaped) were retrieved and all injected with a single spermatozoon. Four
      oocytes showed normal fertilization and developed to day-3 embryos with abnormal
      morphology and were transferred. Two weeks after the embryo transfer, the patient
      had a positive beta-human chorionic gonadotrophin (beta-HCG). The pregnancy was
      uneventful, and a healthy baby boy was delivered at 41 weeks of age by Caesarean
      section. Since fertilization, embryo development, and successful pregnancy was
      achieved in this case, it is recommend that oocytes with extreme morphological
      abnormalities should not be discarded as ICSI may overcome the barriers to
      fertilization and cleavage.

PMID- 16409715
TI  - IUI in male subfertility: are we able to select the proper patients?
AB  - There is at this time no indication as to which semen parameters from the
      fertility work-up discriminate between couples with male subfertility who will
      and will not benefit from intrauterine insemination (IUI). This study evaluated
      the predictive capacity of semen parameters (both pre- and post-wash) and
      antisperm antibodies (ASA) obtained during the fertility workup on IUI outcome in
      couples with male subfertility in a retrospective cohort study. It included 290
      couples, who underwent 722 IUI cycles. The overall ongoing pregnancy rate was 9%
      per cycle. Model I, with female age, duration of subfertility, secondary
      subfertility, the presence of anovulation, cervical hostility and cycle number
      had an area under the curve (AUC) of 0.59. Adding the presence of ASA to this
      model improved the AUC to 0.65 (model II). Further addition of the post-wash
      total motile count (TMC) to the model with ASA (model III) improved the AUC to
      0.67. Using the models to exclude couples from IUI due to low expected pregnancy
      rates would increase the pregnancy rate to 11% per cycle with model I, and to 14%
      per cycle for model II and for model III. In conclusion, in the selection of
      patients with male subfertility for IUI, the use of prediction models including
      ASA can increase the efficiency of IUI.

PMID- 16409716
TI  - Ten years of Swiss National IVF Register FIVNAT-CH. Are we making progress?
AB  - In 2001, analysis of Swiss data collected since 1993 included 1001 treatment
      cycles with IVF, 2217 treatment cycles with intracytoplasmic sperm injection and
      2160 treatment cycles with frozen-thawed embryos or zygotes. IVF cycle number has
      remained constant over the past 10 years, now representing only 18% of the total.
      ICSI treatment cycles have plateaued since 2001. Altogether, patients receive
      1.56 treatment cycles per year, nearly constant since 1995. Mean maternal age has
      increased from 33.9 to 35.7 years, while mean number of recovered oocytes has
      increased by 1.3. Considerable improvement was seen in clinical pregnancy rate
      after 'fresh' treatment cycles since 2000. Mean number of replaced embryos in
      'fresh' treatment cycles has fallen to below 2.5 since 1996, long before the
      legal imposition of the three-embryo transfer limit in 2001, and is still
      decreasing without affecting the consistent twin pregnancy rate of 19%. The
      frequency of ovarian hyperstimulation syndrome has increased three-fold. External
      audits have reduced the mean number of errors per data file by half, and
      increased the number of correct files by 20%. Data collected over this 10-year
      period show that despite the introduction of a restrictive law and increasing
      mean maternal age, the overall clinical pregnancy rate has continued to improve.

PMID- 16409717
TI  - Oxidative stress and its implications in female infertility - a clinician's
      perspective.
AB  - Reactive oxygen species (ROS) have a role in the modulation of gamete quality and
      gamete interaction. Generation of ROS is inherent in spermatozoa and
      contaminating leukocytes. ROS influence spermatozoa, oocytes, embryos and their
      environment. Oxidative stress (OS) mediates peroxidative damage to the sperm
      membrane and induces nuclear DNA damage. ROS can modulate the fertilizing
      capabilities of the spermatozoa. There is extensive literature on OS and its role
      in male infertility and sperm DNA damage and its effects on assisted reproductive
      techniques. Evidence is accumulating on the role of ROS in female reproduction.
      Many animal and human studies have elucidated a role for ROS in oocyte
      development, maturation, follicular atresia, corpus luteum function and
      luteolysis. OS-mediated precipitation of pathologies in the female reproductive
      tract is similar to those involved in male infertility. OS influences the oocyte
      and embryo quality and thus the fertilization rates. ROS appears to play a
      significant role in the modulation of gamete interaction and also for successful
      fertilization to take place. ROS in culture media may impact post-fertilization
      development, i.e. cleavage rate, blastocyst yield and quality (indicators of
      assisted reproduction outcomes). OS is reported to affect both natural and
      assisted fertility. Antioxidant strategies should be able to intercept both
      extracellular and intracellular ROS. This review discusses the sources of ROS in
      media used in IVF-embryo transfer and strategies to overcome OS in oocyte in
      vitro maturation, in-vitro culture and sperm preparation techniques.

PMID- 16409718
TI  - [The present status and outlook of interventional pulmonology in the diagnosis
      and treatment of pulmonary diseases in China].

PMID- 16409719
TI  - [A need to improve the diagnosis of hospital-acquired pneumonia and the rational
      use of antimicrobial agents].

PMID- 16409720
TI  - [Restenosis and its management after metallic stents implantation in benign
      tracheal and main bronchial stenosis].
AB  - OBJECTIVE: To observe the occurrence of restenosis after metallic stents
      implantation in benign tracheal and main bronchial stenosis, and to evaluate the
      therapeutic effects of balloon dilatation, cryotherapy and electrocautery.
      METHODS: Thirty patients with benign tracheal stenosis and 35 patients with main
      bronchial stenosis caused by tuberculosis were treated with metallic stents
      implantation and a follow-up was carried out to observe the occurrence of
      restenosis. Combined balloon dilatation, cryotherapy and electrocautery were used
      to manage the restenosis. The lumen of stenotic segment, dyspnea index and
      pulmonary function were measured before management and after the patient's
      condition became stable. RESULTS: Restenosis occurred in 6 of the 30 patients
      receiving tracheal stenting and in 8 of the 35 patients receiving bronchial
      stenting, the restenosis rates were 20% and 22.86%, respectively. In total, 30
      Chinese-made stents and 36 Ultraflex stents were implanted, and the restenosis
      rate was 20% and 22.2%, respectively (P > 0.05). The restenosis rate was 4/9 in
      the upper segmental tracheal stents, and was 9.09% in the middle-lower segmental
      stents (chi(2) = 5.114, P < 0.05, but chi(c)(2) = 3.100, P > 0.05). The
      restenosis rate was 16.67% in the fibrotic stage of endobronchial tuberculosis
      (EBTB), and was 60% in the inflammatory reaction stage of EBTB (chi(2) = 4.564, P
      < 0.05, but chi(c)(2) = 2.437, P > 0.05). The effective rate was 4/6 in the
      tracheal stenting restenosis patients, and was 2/4 and 2/2 in the upper and
      middle-lower segment groups, respectively. The effective rate was 7/8 in the
      bronchial stenting restenosis patients. After management, the lumen diameter of
      stenotic segment in the tracheal stenting restenosis patients increased from
      (3.33 +/- 1.63) mm to (9.33 +/- 3.98) mm (P < 0.02), the dyspnea index decreased
      from (3.67 +/- 0.52) to (1.50 +/- 1.64) (P < 0.02), the vital capacity (VC)
      increased from (1.39 +/- 0.17) L to (2.43 +/- 0.70) L (P < 0.01), the forced
      expiratory volume in one second (FEV(1)) increased from (1.02 +/- 0.15) L to
      (2.00 +/- 0.72) L (P < 0.02). After management, the lumen diameter of stenosis
      segment in the bronchial stenting restenosis patients increased from (3.00 +/-
      0.76) mm to (7.38 +/- 2.00) mm (P < 0.001), the dyspnea index decreased from
      (1.63 +/- 0.52) to (0.50 +/- 0.76) (P < 0.005), VC increased from (1.74 +/- 0.16)
      L to (2.74 +/- 0.41) L (P < 0.001), FEV(1) increased from (1.41 +/- 0.19) L to
      (2.36 +/- 0.37) L (P < 0.001). CONCLUSION: Restenosis occurred in some patients
      with benign tracheal and tuberculous bronchial stenosis after metallic stent
      implantation. The restenosis rate was higher in the upper tracheal stenosis than
      that in the middle-lower tracheal stenosis. Caution should be taken when metallic
      stents are placed in this part of the trachea. The restenosis rate was higher in
      the inflammatory reaction stage of EBTB than in the fibrotic stage. Effort should
      be made to avoid placing metallic stents at this stage of the disease. Balloon
      dilatation, cryotherapy and eletrocautery are effective methods in managing
      restenosis after stent implantation.

PMID- 16409722
TI  - [The clinical and pathological characteristics and prognosis of pseudomyxoma
      peritonei].
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics,
      treatment measures and prognosis of pseudomyxoma peritonei (PMP). METHODS: The
      clinical records and follow-up data of the patients with PMP were retrospectively
      analyzed. Survival analysis (Kaplan-Meier method and Cox regression) was used to
      investigate the prognosis. RESULTS: Thirty-three patients (twenty-two women,
      eleven men) have a median interval between onset and definite diagnosis of 12
      months with an average age of 50. The main clinical presentation includes
      bloating, abdominal mass and abdominal distention. A delay in diagnosis is common
      and many patients are labeled as other diseases (84.8%). Positive results were
      often found in the assistant examinations such as erythrocyte sedimentation rate,
      gastrointestinal tumor markers (carcinoembryonic antigen, carcinomatous antigen
      19-9 and so on), imaging (B ultrasound and computer tomography) and abdominal
      paracentesis which was usually unsuccessful. The most frequently practiced
      approach is debulking surgery with the main assistant means of chemotherapy which
      was lack of the uniform rationale. Benign type of pathological samples accounts
      for 66.7% of all, while mid-type 21.2% and malignant 12.1%. The general median
      survival time is 70 months with a follow-up rate of 79%. The pathological type
      and chemotherapy are main factors which influence the cumulative survival rate (P
      < 0.05). Up to the end of 2004, sixteen patients died of various complications,
      multiple organ failure and severe infection, while ten patients survival and
      seven patients lost. CONCLUSIONS: PMP is a rare condition of borderline
      malignancy with its unique clinical and pathological characteristics.
      Gastrointestinal tumor markers, imaging and abdominal paracentesis are very
      important to the diagnosis. The existing treatment measures need to be improved
      further. The pathological type and chemotherapy are main factors which influence
      the prognosis.

PMID- 16409721
TI  - [A study of pulmonary inflammatory reaction induced by N-protein of SARS-CoV in
      rat models and effects of glucocorticoids on it].
AB  - OBJECTIVE: To study the pulmonary inflammatory reaction induced by N-protein of
      SARS-CoV in rat models and the effects of glucocorticoids on the inflammatory
      reaction. METHODS: The pulmonary inflammatory reaction in rat models were induced
      by intratracheal instillation of N-protein of SARS-CoV with a dose of 0.2 mg/kg.
      The rats were randomly divided into four groups: normal saline control group (Nc
      group), N-protein group 1 (P1 group, 6 h), N-protein group 2 (P2 group, 24 h),
      and N-protein + dexamethasone group (P + D group, dexamethasone 10 mg/kg
      intraperitoneally). The blood samples, bronchial alveolar lavage fluid (BALF) and
      lung tissue were collected after challenge. The cytological and histopathologic
      changes of lung tissues were observed and the wet/dry ratios (W/D) of lung tissue
      were determined. The interleukin (IL)-6, IL-10 and transforming growth factor
      beta1 (TGF-beta1) of serum and BALF were measured by ELISA. RESULTS: (1) Compared
      with the percentage of peripheral blood lymphocytes in Nc group [(68.42 +/-
      13.07)%], that in P2 group [(50.50 +/- 14.36)%] was significantly decreased (P <
      0.05); compared with Nc group and P2 group, that in P + D group was furthermore
      significantly decreased (P < 0.01). Compared with the total WBC of peripheral
      blood in Nc group [(5.86 +/- 2.25) x 10(9)] and P2 group [(4.83 +/- 1.49) x
      10(9)], that in P + D group [(1.96 +/- 1.30) x 10(9)] was significantly decreased
      (P < 0.01). (2) Compared with the total WBC of BALF in Nc group [(95 +/- 29) x
      10(7)], that in P2 group [(160 +/- 60) x 10(7)] was significantly increased (P <
      0.05); but compared with P2 group, that in P + D group [(62 +/- 23) x 10(7)] was
      significantly decreased (P < 0.05). Analysis of BALF differential cell counts
      showed that the majority of cells were alveolar macrophages in all groups. (3)
      The W/D ratios of lung tissue in both P1 and P2 group [(5.18 +/- 0.29) and (5.19
      +/- 0.34), respectively] after N-protein challenge were significantly increased
      than that in Nc groups [(4.77 +/- 0.27), P < 0.05]; the W/D ratio in P + D group
      (4.70 +/- 0.18) was significantly decreased than that in P2 group (P < 0.01). (4)
      Compared with Nc group, the levels of IL-6, IL-10, TGF-beta1 in both serum and
      BALF of P1 group were significantly increased (P < 0.01), and the levels of these
      cytokines in P2 group were significantly higher than those in P1 group (P <
      0.01), but significantly lower in P + D group compared with P2 group (P < 0.01).
      CONCLUSIONS: The N-protein of SARS-CoV had pathogenicity and could induce obvious
      pulmonary inflammatory reaction and acute lung injury, which were related to the
      increase and imbalance of pro-inflammatory and anti-inflammatory cytokines.
      Glucocorticoids could effectively alleviate the pulmonary inflammatory reaction
      induced by N-protein of SARS-CoV.

PMID- 16409724
TI  - [A clinical analysis of 57 cases of abdominal tuberculosis].
AB  - OBJECTIVE: To explore the clinical characteristics and diagnosis methods of
      abdominal tuberculosis. METHODS: The clinical characteristics of abdominal
      tuberculosis in 57 cases proved by histopathology between 1958-2004 were
      retrospectively analyzed. RESULTS: There were 39 cases of tuberculosis of the
      liver, 5 cases of the spleen, 8 cases of the pancreas, 3 cases of the stomach, 1
      case involved both liver and spleen and 1 case involved both liver and stomach.
      Twenty-six patients were males and 31 female; with ages ranged from 17 to 68
      years (mean 40.7 years) and most cases (71.9%) having extra-abdominal
      tuberculosis. Fever (75.4%), fatigue, anorexia, night sweating, weight loss
      (82.5%) and hepatosplenomegaly (57.9%) were the major clinical manifestations.
      Elevated erythrocyte sedimentation rate (ESR) (59.6%) and abdominal mass (64.9%)
      were found in most of the patients. CONCLUSIONS: The diagnosis of abdominal
      tuberculosis should be considered in all patients with fever of unknown origin,
      especially in those associated with hepatosplenomegaly, increased ESR and
      abdominal mass. Aspiration biopsy and laparotomy can provide correct diagnosis.
      The disease can be effectively treated with surgical intervention and
      antituberculous chemotherapy.

PMID- 16409725
TI  - [The differential features of bone marrow morphology of several rare infectious
      disorders].
AB  - OBJECTIVE: To facilitate the diagnosis of histoplasmosis, kala-azar,
      penicilliosis marneffei, toxoplasmosis and cryptococcosis with the help of bone
      marrow morphology. METHOD: The clinical features and bone marrow cytomorphology
      in 7 cases of histoplasmosis, 1 case of kela-azar, 1 case of penicilliosis
      marneffei, 2 cases of toxoplasmosis and 3 cases of cryptococcosis were studied.
      RESULTS: In the bone marrow examination, the form of histoplasma capsule was
      ovoid with a colorless circle. The morphology of Leishmania donovani was similar
      to that of histoplasma capsule except that there were terkinetoplasts present in
      the former. Sausage form and central cross wall were signs of Penicillium
      marneffei. Toxoplasma gondii looked like a banana and cryptococcus neoformans was
      larger than the others and had a thick capsule. CONCLUSION: The examination of
      bone marrow is important to the diagnosis of these rare infectious diseases.

PMID- 16409727
TI  - [Expression and significance of brain-derived neurotrophic factors and receptors
      in multiple myeloma].
AB  - OBJECTIVE: To investigate the expression of brain-derived neurotrophic factor
      (BDNF) and its receptors in multiple myeloma (MM) cells and the biological
      effects of BDNF on MM cells. METHODS: Transcription and protein expression of
      BDNF and its receptors (TrkB and P75(NTR)) in human myeloma cell lines (HMCLs)
      was determined with RT-PCR and Western blotting. BDNF levels in culture
      supernatant was determined with enzyme-linked immunosorbent assay. The expression
      of BDNF and TrkB by myeloma cells was studied with immunohistochemistry in bone
      marrow biopsy samples from 15 patients with MM. The effect of BDNF on the in
      vitro proliferation of HMCLs (RPMI 8226, U266, KM3) was examined with 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The effect of
      BDNF on HMCLs migration was studied with modified Boyden chamber assay. RESULTS:
      BDNF was expressed and secreted by HMCLs in high concentrations up to 14.7
      microg/L. Furthermore, expression of its high affinity receptor TrkB was observed
      in HMCLs. BDNF expression by myeloma cells was demonstrated in 12 of the 15
      patients with MM (80%), TrkB expression was demonstrated in all the 15 patients
      (100%), whereas control bone marrow samples showed weaker expression of BDNF in 2
      of 9 (22.2%) and TrkB in 4 of 9 (44.4%). Functional studies demonstrated that
      BDNF has strong proliferative effects on HMCLs and proliferation of RPMI 8226 was
      enhanced by BDNF in a time- and dose-dependent manner. Moreover, BDNF has
      chemotactic properties on HMCLs. The maximal responses were seen at 50 microg/L
      for RPMI 8266 (P < 0.05) and 25 microg/L for KM3 cells (P < 0.01) as compared
      with nonstimulated controls. CONCLUSION: BDNF and its high affinity receptor TrkB
      are co-expressed by MM cells. BDNF appears to have a major contribution to the
      pathophysiology of MM leading to proliferation and migration of MM cells. These
      provide the framework for novel therapeutic strategies targeting BDNF/TrkB
      signaling in MM.

PMID- 16409728
TI  - [A study of antiendothelial cell antibodies in Behcet's disease].
AB  - OBJECTIVE: To investigate the clinical significant of antiendothelial cell
      antibodies (AECA) in Behcet's disease. METHODS: With human umbilical vein
      endothelial cell as substrate cell, sera from 59 Behcet's disease patients were
      detected for the presence of AECA by using fixed cell-ELISA. The associations of
      AECA to clinical disease activity were analyzed. In addition, Sera from other 70
      systemic vasculitis (including 28 Takayasu arteritis, 20 Wegener's
      granulomatosis, 8 polyarteritis nodosa, 9 microscopic polyangiitis, 5 Churg
      Strauss syndrome), 57 systemic lupus erythematosus (SLE), 25 rheumatoid arthritis
      and 85 healthy donors were screened for AECA. The associations of AECA to
      clinical disease activity were analyzed. RESULTS: The prevalence of AECA by human
      umbilical vein endothelial cell cell-ELISA was 47.5% in Behcet's disease.
      Compared with patients with rheumatoid arthritis (4.0%) and normal group (1.2%),
      AECA were more frequently found in patients with Behcet's disease, other systemic
      vasculitis (68.6%) and SLE (45.7%) (P < 0.01). The positive result on pathergy
      testing was more frequently found in AECA-positive patient with Behcet's disease
      (P < 0.05). After the treatment, patients with active disease entering remission
      showed a decrease in both AECA titers and the mean level of ESR (P < 0.05).
      CONCLUSIONS: AECA could be found more frequently in patients with Behcet's
      disease, associated closely with disease activity, which suggest that AECA may be
      used as an index in monitoring disease activity and effect of therapy in Behcet's
      disease. But AECA could also be found in other systemic vasculitis and SLE.

PMID- 16409729
TI  - [The relationship between the five beta-fibrinogen gene polymorphisms and
      cerebral infarction].
AB  - OBJECTIVE: To investigate the relationship among beta-fibrinogen (Fg)
      concentration, related gene polymorphisms (including -148C/T, -249C/T, -455G/A,
      448G/A, 1689T/G) and cerebral infarction. METHODS: Fg level and its five gene
      polymorphisms were analyzed with by polymerase chain reaction-restriction
      fragment length polymorphism in 132 patients with cerebral infarction, 79
      patients with other neurological diseases and 92 healthy elders. RESULTS: The
      plasma Fg level in cerebral infarction patients was significantly higher than
      that in the patients with other neurological diseases or healthy elders (P <
      0.05). In the three groups, the plasma Fg levels in individuals with T-148 and A
      455 alleles were higher than those in individuals without T-148 and A-455 alleles
      (P < 0.05). However, there were no statistically significant differences in the
      genotype and allele frequencies in the five mutation gene polymorphisms among the
      three groups (P > 0.05). CONCLUSIONS: Cerebral infarction is a multifactorial
      disease and an increased Fg level is a risk factor for cerebral infarction. T-148
      and A-455 allele can lead to elevated Fg concentration.

PMID- 16409730
TI  - [Citation analysis of published articles in the Chinese Journal of Internal
      Medicine in the period of 2000-2004].
AB  - OBJECTIVE: To identify and analyze the scientific level and quality of the
      articles published in Chinese Journal of Internal Medicine. METHOD: Using the
      database of the Chinese Medical Citation Index (CMCI), the numbers and
      distribution of the cited original articles in Chinese Journal of Internal
      Medicine from 2000 to 2004 were analyzed according to the method of citation
      analysis. RESULT: The percentage of cited papers in all the published articles
      was 47.10% during the period, the average times of citation of an original
      article by other researchers is 4.30 and the top cited frequency was 133. There
      were 250 articles being cited 5 or more (25.43% of the total papers), and the
      times of citation from them were 2834 (67.01% of the total). 983 cited articles
      were written by 845 authors from different countries. The author of the most
      frequently cited articles wrote 6 papers and the authors with one cited paper
      were 751 (88.88% of all the authors). The cited authors were from 31
      municipalities and provinces as well as from other countries. Beijing, Guangdong
      and Shanghai were in the front of the list of places with authors being
      frequently cited. Beijing was the top of the rank (44.74% of total authors).
      There were 266 institutes cited and the most frequently cited institute was
      Peking Union Medical College Hospital of Peking Union Medical College and Chinese
      Academy of Medical Sciences. There were 685 citing journals and the self-citing
      rate is 3.52%. CONCLUSIONS: The Chinese Journal of Internal Medicine has
      published high quality articles. As a core medical journal, it is the one of the
      most important information resources for the medical researchers.

PMID- 16409748
TI  - [Diagnosis of portal hypertension caused by splenic vein thrombosis].

PMID- 16409749
TI  - [Fetal growth and adult obesity].

PMID- 16409753
TI  - [Progresses and challenges in genetic studies of glaucoma].
AB  - Glaucoma is one of the leading causes of irreversible blindness. The genetic
      changes play an important role in the pathogenesis of glaucoma. Progress in human
      genome project (HGP) and the application of molecular genetics in the study of
      glaucoma has leaded to an important progress in the understanding of etiology of
      glaucoma. It is still difficult to predict the influence of these progresses on
      the early diagnosis, prevention and treatment of glaucoma. However, this may
      provide a series of problem that require exploration and shows the changing
      direction of glaucoma study in the future.

PMID- 16409754
TI  - [Primary angle closure - a new term in the definition of primary angle closure
      glaucoma?].
AB  - A new definition and classification system was proposed recently for primary
      angle closure glaucoma. This system emphasizes on the characteristic progressive
      end-organ damage - "glaucomatous optic neuropathy", and attempts to adopt a
      uniform definition of glaucoma, synonymous with primary open angle glaucoma. This
      approach represents a departure from convention, in which individuals with a
      narrow drainage angle combine with either raise intraocular pressure or
      peripheral anterior synechiae but without glaucomatous optic neuropathy, are said
      to have primary angle closure rather than primary angle closure glaucoma.
      Although the use of this definition has been adopted by the American Academy of
      Ophthalmology and Southeast Asia Glaucoma Interest Group, it is still debatable
      on whether this should be adopted in China. We attempt to describe the background
      of the development of this new classification scheme, discuss its advantages and
      challenges.

PMID- 16409755
TI  - [Statistical quality requires improvement in ophthalmic research].
AB  - The improper use of statistical analysis method and inadequate quality of
      experimental design are common in ophthalmic research. These problems originated
      from ignoring the importance of statistics or have a bias against the statistics
      by the researcher. Therefore, the misunderstanding of statistics must be cleared
      up, it is important for the researcher to familiar with statistical knowledge,
      instead of simply relying on the cooperation with statistics specialists.
      Researcher should devote much attention to the study of statistics and enhance
      the ability to apply it in practice. Statistics is not only one of the supports
      of evidence-based medicine, but it is also very important in keeping sustainable
      scientific development of science.

PMID- 16409756
TI  - [A preliminary study on gene mutation and its function in a large family (GZ.1
      pedigree) with open-angle glaucoma].
AB  - OBJECTIVE: To determine the causative mutation of myocilin gene and to
      investigate its pathogenic function in a large Chinese pedigree (GZ.1) with
      familial open-angle glaucoma. METHODS: Genome-wide scanning was performed and the
      Lod scores were calculated. Candidate gene was amplified and screened for
      mutations using direct sequencing. To elucidate its expression, distribution and
      cytotoxicity of mutant myocilin, human trabecular cells (HTM) cells were
      transfected with pcDNA-wild-type and mutant myocilin vectors using liposomes.
      RESULTS: Mutation analysis of the myocilin gene showed a C-to-T transition at the
      1, 109 th nucleotide in exon 3 resulting in a change of amino acid from proline
      to leucine (Pro370Leu). This mutation cosegregated with all affected individuals
      (16/16) and never presented in unaffected individuals (0/8). In transfected HTM
      cells, the mutant myocilin protein was not correctly processed in ER and
      accumulated as aggresome-like structures in the cytoplasma instead of being
      secreted. In addition, the expression of mutant protein also led to apoptosis of
      trabecular cells and the occurrence of. CONCLUSION: The mutation of Pro370Leu in
      myocilin gene could cause the accumulation of misfolding myocilin protein in HTM
      cells, which might lead to glaucoma in GZ.1 pedigree.

PMID- 16409760
TI  - [Clinical observation of needle revision and 5-fluorouracil subconjunctival
      injection on the dysfunctional filtering blebs].
AB  - OBJECTIVE: To investigate the efficacy of needle revision with 5-fluorouracil (5
      FU) on the dysfunctional filtration blebs after trabeculectomies and to assess
      the factors that may impact the success. METHODS: Fourty eyes of 34 patients
      underwent the needle revision of the malfunctional blebs with 5-FU at clinic
      visits in 2 - 8 weeks immediately after trabeculectomies and were followed up for
      12 weeks. RESULTS: After revision through needling procedures, the blebs were
      diffused and elevated in 26 eyes, thinned and multisystem in 9 eyes, thickened
      and focalized or invisible in profile in 5 eyes. Intraocular pressures (IOPs)
      were significantly (P < 0.01) lowered from (23.6 +/- 2.1) mm Hg (1 mm Hg = 0.133
      kPa) of pre-needling to (16.3 +/- 2.9) mm Hg of post-needling in 35 functional
      filtering blebs. The Kaplan-Meier survival curve for the 40 eyes showed a success
      rate of (87.51 +/- 5.23)% within the follow-up time. Logistic regression did not
      show significant difference in needle revision among the types of glaucoma, the
      history of intraocular surgery, and the ages of patients. However, poorer
      responses were observed following greater intervals of needling operation from
      previous trabeculectomy (P = 0.046). The time interval for the median efficacy
      level is 5.9 weeks. Subconjunctival hemorrhage occurred in 6 eyes during the
      needle revision, and no other post-needling complications were found during the
      follow-up time. CONCLUSIONS: The needle revision combined with 5-FU is an
      effective, safe, and simple method of improving early dysfunctional filtration
      blebs after trabeculectomies. The success rate of needle revision was about 50%
      at 6 weeks and the delay of needle revision may result in poor responses.

PMID- 16409758
TI  - [Preliminary study of inhibition of human Tenon's capsule fibroblasts in vitro by
      RNA interference targeting IKK-beta].
AB  - OBJECTIVE: To determine whether small interference RNA (siRNA) targeting the
      inhibitor of kappaB kinase-beta (IKK-beta) could be used to suppress the IKK-beta
      expression, and inhibit the proliferation of human Tenon's capsule fibroblasts in
      vitro. METHODS: IKK-beta specific siRNA designed from the human gene sequence was
      transfected into the cultured human Tenon's capsule fibroblasts, and a non
      targeted siRNA was transfected as a negative control. The mRNA of IKK-beta was
      assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the
      protein expression was determined by Western blotting. Cell viability of the
      cultured human Tenon's capsule fibroblasts with series of RNA interference at 5,
      10, 25, 50, 100, and 200 nmol/L was evaluated by MTT assay 48 hours after
      transfection. RESULTS: The expression of IKK-beta was significantly (P < 0.05)
      suppressed at both mRNA and protein levels after transfection. The proliferation
      of the cultured human Tenon's capsule fibroblasts was inhibited at all the
      transfected concentrations at different rates (10.72%, 23.35%, 30.84%, 51.25%,
      50.06% and 49.63% respectively). The highest level of inhibition was observed at
      50 nmol/L of siRNA concentration. CONCLUSIONS: IKK-beta specific siRNA is
      effective in suppressing the IKK-beta expression and inhibiting the proliferation
      of the cultured human Tenon's capsule fibroblasts. RNA interference may offer a
      new alternative to post-operational management of scar tissue formation.

PMID- 16409761
TI  - [The evaluation of visual quality in keratoconus eyes corrected by rigid gas
      permeable contact lens].
AB  - OBJECTIVE: To evaluate the visual quality in keratoconus eyes corrected by rigid
      gas-permeable contact lens (RGPCL) and spectacles. METHODS: Corrected visual
      acuity, corneal topography, wavefront aberration and contrast sensitivity were
      measured in 27 keratoconus patients (54 eyes) before and after the fitting of
      RGPCL. RESULTS: The inclusive keratoconus eyes were divided mild 30 eyes,
      moderate 13 eyes and sever 11 eyes. The average myopia and average astigmatism
      were (6.92 +/- 3.66) D and (5.75 +/- 1.85) D respectively. Uncorrected visual
      acuity (VA) in 96.3% keratoconus eyes was <or= 0.3. RGPCL corrected VA was
      increased significantly compared with spectacles corrected VA. The VA in 59.3% of
      eyes corrected by spectacles were >or= 0.6, while 100% by RGPCL. The VA in 20.4%
      of eyes corrected by spectacles were >or= 1.0, while 66.7% by RGPCL. Corneal
      topography study showed corneal toricity decreased to <or= 0.75 D in RGPVA group.
      Ocular surface was changed to spherical and regular shapes. Root-mean-square
      (RMS) of wavefront aberration decreased significantly from (3.63 +/- 2.08) microm
      (without RGPCL) to (1.39 +/- 0.82) microm (with RGPCL) (P < 0.01). RMS of Zernike
      function in each order was decreased as well, second order from (2.64 +/- 1.74)
      microm to (0.81 +/- 0.66) microm, total high order from (2.35 +/- 1.57) microm to
      (1.10 +/- 0.62) microm, third order from (1.78 +/- 1.28) microm to (0.68 +/-
      0.39) microm With RGPCL fitting, contrast sensitivity curve (light on and light
      off) were significantly higher than that with spectacles in whole range of
      frequency, especially in middle and high frequency. CONCLUSIONS: Corneal
      distortion induced high corneal irregular astigmatism is the most frequent cause
      of increase of aberration and reduced ocular optical quality in keratoconus.
      Proper RGPCL fitting provides an effective method in reshaping of ocular surface
      combined with tear film. RGPCL could reduce aberrations and corneal astigmatism,
      improve optical quality, and finally, increase visual acuity and contrast
      sensitivity.

PMID- 16409762
TI  - [The use of CAD/CAM techniques in the repair of complex orbital fractures and the
      reposition of enophthalmos].
AB  - OBJECTIVE: To reconstruct the three-dimensional (3 D) imaging and computer
      generated models of the complex orbital fractures, and to develop a Computer
      Aided Design/Computer-Aided Manufacture (CAD/CAM) system for orbital fracture
      repair. METHODS: We carried out study on 12 patients with orbital fractures from
      August 2003 to March 2004 in the Ninth People's Hospital. Before the orbital
      fracture repair, helical computer tomography scanning was applied to acquire the
      3 D imaging data of the patient's orbits. The 3 D imaging data were then
      transferred to a CAD/CAM interactive program for image processing, which then
      designed and produced a stereolithography model mathematically. Using the
      designed software, the repair of orbital fractures could be planned with the
      computer. At the same time, the orbital cubane was calculated. Then the operation
      was performed and the effect of the therapy was evaluated. RESULTS: Using the
      CAD/CAM system of orbital fracture repair, the 3 D image of the orbit could be
      reconstructed, and the orbital cubane could be calculated accurately. The
      preoperative surgical plan was put into reality. After the orbital fracture
      repair, all cases received excellent appearance and function. This system had
      proved to run smoothly and accurately, and could easily be controlled.
      CONCLUSIONS: The CAD/CAM system of the orbital fracture repair may be proved as
      one of the most useful clinical tools for orbital surgery.

PMID- 16409763
TI  - [Application of lacrimal plug for dry eye patients].
AB  - OBJECTIVE: To observe the availability and efficacy of Smart PLUG in lacrimal
      plug in the treatment of serious dry eye. METHODS: Lacrimal plug was applied in
      43 patients (72 eyes) in our clinic from July to October in 2004. Questionnaire
      was used in these patients before the surgery 3 days and repeated after surgery 1
      week and 3 months. Slit lamp microscope examination, fluorescent staining for
      tear break-up time (BUT), Schirmer test I (STI), impression cytology (IC) were
      carried out at the same time. RESULTS: Questionnaire indicated most patients
      complained about dry eye, foreinbody sensation, asthenopia and red eye. These
      symptoms were relieved obviously after the application of lacrimal plug. Compared
      with pre-operation, tear production was increased significantly on the surface of
      eyes and the defect of corneal epithelium was healed in 37 patients (62 eyes).
      Compared with pre-operation, BUT and STI were increased and elongated on these
      patients, IC suggests squamous metaplasia of epithelial layer of conjunctiva in
      these patients was improved. CONCLUSIONS: Symptoms of patients suffered from dry
      eye were relieved obviously by using Smart PLUG. Therefore lacrimal plug can be
      used for patients with serious dry eye by improving tear volume and tear film
      stability.

PMID- 16409764
TI  - [Optical penetrating keratoplasty in eyes with severe keratomycosis after
      therapeutic keratoplasty].
AB  - OBJECTIVE: To observe and evaluate secondary optical penetrating keratoplasty
      (PKP) in the eyes with severe keratomycosis after therapeutic keratoplasty using
      cryopreserved donor tissue. METHOD: There were 35 eyes in 35 cases for whom
      therapeutic PKP using cryopreserved donor tissue had been carried out to treat
      severe fungal keratitis. At least 6 months after the PKP, when the fungal
      infection had been eradicated and ocular inflammation had resolved, a secondary
      optical penetrating keratoplasty was further performed for visual rehabilitation.
      If the crystal lens was found to be opaque, it was also simultaneously removed
      through extracapsular cataract removal with an IOL implantation. Surgical or
      postoperative complications, visual outcome, graft rejection episode, and graft
      survival were analyzed. RESULTS: Among 35 eyes, 18 eyes received optical PKP
      only, and 17 received combined optical PKP with ECCE and IOL implantation. During
      the follow-up period of 6.8 - 36.8 (15.7 +/- 7.6) months after optical PKP, 3
      eyes experienced graft failure due to immunologic rejection and 32 retained clear
      grafts. Postoperative visual acuity was 0.4 or better in 24 eyes, and 0.1 or
      better in 32 eyes, and less than 0.1 in 3 eyes. CONCLUSIONS: Optical PKP
      performed in the eyes after therapeutic PKP due to severe fungal keratitis can
      recover satisfactory visual acuity, with low frequency of graft rejection, long
      term graft survival and few complications.

PMID- 16409765
TI  - [Multilayer amniotic membrane transplantation for treatment of necrotizing herpes
      simplex stromal keratitis].
AB  - OBJECTIVE: To evaluate the efficacy of multilayer amniotic membrane
      transplantation (AMT) combined with antivirus and corticosteroid drug to treat
      necrotizing herpes simplex stromal keratitis. METHODS: Thirteen patients (13
      eyes) of necrotizing stromal keratitis were referred to Shandong Eye Institute
      and Qingdao Eye Hospital between January 2003 and April 2004. The course of
      disease was 3 - 22 months (mean 15 months). Corneal inflammation persisted and
      corneal ulcer progressed despite topical and systemic antiviral treatment for
      over 1 weeks. Multilayer amniotic membrane transplantation was performed after
      excluding of bacterial and fungal infection by microbiologic studies including
      smears and cultures of necrotic corneal tissue and confocal microscope. Topical
      and systemic antiviral medications were given with adjuvant corticosteroid
      eyedrops postoperatively. We investigated the healing of corneal ulcer and
      improvement of stromal edema with slit lamp biomicroscope, the integrity of
      corneal defect with fluorescein staining, the migration of healthy corneal
      epithelial cells and transformation of amniotic membrane with confocal
      microscopy. All patients were followed up for 3 - 13 months (mean 10 months).
      RESULTS: Corneal ulcer healed within 1 - 3 weeks postoperatively with negative
      fluorescein staining. Corneal stromal edema faded away within 1 month.
      Superficial amniotic membrane patches dissolved or shed on postoperative day 7 -
      10, while the deeper grafts were adhered into the ulcer and fused with the
      surrounding fibroblasts. One of these grafts remained in situ more than 3 months.
      Confocal microscope examination indicated flat epithelial progenitor cells on the
      surface of residual amniotic membrane. Corneal transparence was achieved in 7
      eyes, macula in 4 eyes and leucoma in 2 eyes 3 months after the operation. No
      recurrence of necrotizing stromal keratitis was occurred in 13 patients during
      the follow-up period. CONCLUSION: Multilayer AMT combined with antivirus and
      corticosteroid treatment is an effective method to treat necrotizing herpes
      simplex stromal keratitis.

PMID- 16409767
TI  - [The ultrastructure changes of rabbit retina after periodical vacuum suction].
AB  - OBJECTIVE: To study the effects of periodical vacuum-suction of different
      pressures on the ultrastructure of rabbits' retina. METHODS: Rabbits involved in
      the present study were divided into a control group and four treatment groups,
      which were treated with vacuum-suction of different pressures through scleral
      suction ring. The suction pressure was increased at a rate of 100 mm Hg/3 sec (1
      mm Hg = 0.133 kPa) and reached (200 +/- 20) mm Hg (group I), (300 +/- 20) mm Hg
      (group II); (400 +/- 20) mm Hg (group III) and (500 +/- 20) mm Hg (group IV). The
      suction pressure was maintained for 5 seconds before released to zero. The
      corresponding intraocular pressure examined by Tonopen was 35 mm Hg, 45 mm Hg, 55
      mm Hg and 75 mm Hg in these 4 groups, respectively. This circle was repeated for
      10 times with 1 minute interval. The test was repeated every other day. The
      retina was examined by electron microscope after 2 weeks. RESULTS: There was no
      obvious difference in the retina ultrastructure between the control group and
      group I. The retina ultrastructure changed slightly in group II which showed more
      active metabolism. Some significant changes were found in group III and group IV
      with cell necrosis in group IV. CONCLUSION: Different elevations of intraocular
      pressure following periodical vacuum-suction have different effects on the retina
      of rabbit. Pressure less than 45 mm Hg has almost no effect, but some effects
      appear at 55 mm Hg pressure, and obviously damages are caused by 75 mm Hg
      pressure.

PMID- 16409766
TI  - [The role of specific ROCK inhibitor in the prevention of experimental PVR in
      rabbits].
AB  - OBJECTIVE: To determine the effect of Y27632, a specific inhibitor of p160 Rho
      associated coiled-coil forming protein kinase (ROCK), on experimental rabbit PVR.
      METHODS: Cultured rabbit retinal pigment epithelial cells were used in the
      experiments. The effects of Y27632 on RPE alpha-SMA (smooth muscle actin) stress
      fiber formation were studied by immuno-fluorescent staining. An in vitro type I
      collagen gel contraction assay and MTT assay were used to detect the effect of
      Y27632 on RPE cell contractile force and proliferation. Cultured 6 th passage
      rabbit RPE cells were injected intravitreally to induce the PVR model and then
      followed injection of 50 micromol/L of Y27632. The presence of tractional retinal
      detachment (TRD) was assessed to evaluate the effect of this agent in vivo.
      Electroretinography and histological studies were performed after intravitreal
      injection of Y27632 into untreated eyes to evaluate toxicity. RESULTS: The
      results showed that Y27632 disrupted SMA stress fiber formation in the cultured
      RPE cells and impaired contractile force generated by RPE cells (t = 16.212, P <
      0.01). Development of TRD was significantly reduced (P < 0.01) with 50 micromol/L
      of Y27632. No obvious histological or retinal functional damage was found in the
      Y27632-treated group. CONCLUSION: p160 ROCK specific inhibitor Y27632 decreased
      contractile force generated by RPE cells and attenuated PVR without significant
      side effect in rabbit. This reagent could be potential therapeutically method in
      the treatment of PVR.

PMID- 16409768
TI  - [Inhibition of rat corneal neovascularization by inhibitor of nuclear factor
      kappaB].
AB  - OBJECTIVE: To observe the effects and mechanism of pyrrolidine dithiocarbamate
      (PDTC) on inhibiting corneal neovascularization. METHODS: The corneal
      neovascularization was induced by alkali burn in 48 Sprague-Dawley rats. The rats
      were randomly divided into 4 groups, 12 rats in each group. The PDTC eye drops
      with different concentrations were applied four times daily during days 0 - 28 in
      each group: 0.5 mg/ml in group A, 1 mg/ml in group B, 2 mg/ml in group C and 0.9%
      sodium chloride in group D (control). The development of corneal
      neovascularization and corneal opacity were observed daily with slit lamp.
      Corneas were excised at day 4 and 28 (six eyes were selected randomly in each
      group per time) for histopathological examinations. The expression of nuclear
      factor-kappaB (NF-kappaB) in the cornea was examined by Western Blot. RESULTS:
      The corneal neovascularization area in groups B and C were significantly smaller
      than that in the control group (P < 0.01). The corneal opacification and
      inflammation level in groups B and C were also lower than that in the control
      group. No significant difference was found in corneal neovascularization areas
      and corneal opacification levels between group A and group D (P > 0.05). The
      activity of NF-kappaB in groups B and C was significantly lower than that of
      group D. No significant difference in NF-kappaB could be detected between group A
      and group D. CONCLUSION: Topical application of PDTC has significant effects on
      the inhibition of activation of NF-kappaB and cornea neovascularization.

PMID- 16409776
TI  - [Advances in uveitis study].
AB  - Uveitis is one of the important causes of blindness in the world. Uveitis has
      been generally defined as the inflammation occurring in the intraocular tissues.
      The causes and entities of uveitis have changed over time. The mechanism for the
      pathogenesis of uveitis has been extensively studied and great achievement has
      been obtained during recent years. Novel techniques for uveitis diagnosis and the
      application of immunoregulatory and biologic agents have improved the treatment
      for the uveitis patients.

PMID- 16409777
TI  - [The prevention, treatment and future study of asthma in China].

PMID- 16409781
TI  - [Effect of doxofylline on calcium-activated potassium channels in human
      peripheral blood eosinophils in asthma].
AB  - OBJECTIVE: To study the effects of doxofylline on calcium-activated potassium
      (K(Ca)) channels of human peripheral blood eosinophils in asthma. METHODS:
      Peripheral blood eosinophils from patients with asthma were isolated and divided
      equally into two groups, a control group and a doxofylline incubated group. The
      data were recorded using cell-attached configuration of patch-clamp technique and
      the kinetic changes of K(Ca) channels activated by 0.2 micromol/L platelet
      activating factor (PAF) were compared. RESULTS: As compared with the control
      group, the open probability of the K(Ca) channels decreased from 0.135 +/- 0.021
      to 0.044 +/- 0.018, the open time from (5.75 +/- 0.40) ms to (2.39 +/- 0.13) ms,
      while the close time increased from (2.17 +/- 0.50) ms to (23.73 +/- 2.50) ms in
      the doxofylline incubated group. The differences were significant between the two
      groups (all P < 0.05). CONCLUSION: Doxofylline could decrease the open
      probability of the channels as a result of both the shortening of open period and
      the prolongation of close time.

PMID- 16409782
TI  - [The relationship between leukemia inhibitory factor and neurokinin receptors in
      a rat model of asthma].
AB  - OBJECTIVE: To study the expression of leukemia inhibitory factor (LIF) and
      neurokinin receptors (NKR) in the lungs of asthmatic rats, and to evaluate the
      role of LIF in airway neurogenic inflammation. METHODS: Twenty-four Wistar rats
      were randomly divided into a control group (group A, n = 8), an asthma group
      (group B, n = 8) and a dexamethasone treated group (group C, n = 8). The rat
      asthmatic model was made by intraperitoneal injection and nebulized aspiration of
      ovalbumin (OVA) at the concentrations of 10% and 1% respectively. Expression
      levels of lung LIF, NK-1R and NK-2R were detected by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot two weeks after challenge,
      and the localization of NK-1R was determined by immunohistochemistry. RESULTS:
      After challenge, the expressions of lung LIF mRNA in group A, B and C were 0.240
      +/- 0.020, 0.510 +/- 0.130, 0.180 +/- 0.050, and protein levels were 23 110 +/- 8
      018, 40 832 +/- 12 964, 16 160 +/- 2 108 respectively. The expressions of lung NK
      1R mRNA in group A, B and C were 0.240 +/- 0.020, 1.040 +/- 0.480, 0.170 +/-
      0.040, and protein levels were 16 538 +/- 4 342, 32 292 +/- 4 564, 15 018 +/- 1
      488 respectively. The mRNA and protein levels of LIF and NK-1R in group B were
      significantly elevated as compared with group A and C (all P < 0.01). The
      expressions of lung NK-2R mRNA in group A, B and C were 0.240 +/- 0.040, 0.200 +/
      0.030 and 0.210 +/- 0.040, and no difference was found among three groups (all P
      > 0.05). In group B, there was a positive correlation between LIF and NK-1R at
      mRNA (r = 0.850, P < 0.01) and protein (r = 0.868, P < 0.01) levels respectively.
      NK-1R immunoreactivity was observed primarily in bronchial epithelial cells.
      CONCLUSION: LIF and NK-1R were excessively expressed and closely correlated in
      lungs of the rat asthmatic model, suggesting that LIF may be involved in
      modulating airway neurogenic inflammation.

PMID- 16409783
TI  - [Pulmonary vascular remodeling and protein kinase C-alpha expression in chronic
      smoke exposure and/or hypoxia rats].
AB  - OBJECTIVE: To investigate pulmonary vascular remodeling and protein kinase C
      alpha (PKC-alpha) expression in chronic smoke exposure and/or hypoxia rats.
      METHODS: Fifty-six male Wistar rats were randomly divided into seven groups:
      control group (C group), smoke exposure groups (S(4W), S(8W) group), hypoxia
      groups (H(4W), H(8W) group), smoke exposure plus hypoxia groups (SH(4W), SH(8W)
      group). Wistar rats were exposed to cigarette smoke and/or hypoxia air [O2 (10.0
      +/- 0.5)%] for 4 to 8 weeks. A method by right cardiac catheterization was used
      for measuring mean pulmonary artery pressure (mPAP). Right ventricle (RV), left
      ventricle (LV) plus interventricular septum (S) were split and weighed and right
      ventricular hypertrophy index (RVHI) was calculated. To evaluate vascular
      remodeling, alpha-smooth muscle actin (alpha-SM-actin) staining and count of the
      percentage of muscularized small pulmonary arteries which was determined by
      morphometric analysis of histological sections were used. Pulmonary artery smooth
      muscle cell (PASMC) apoptosis was detected by in situ end labeling technique
      (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) staining.
      Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence
      staining and Western blot analysis were used for the detection of PKC-alpha mRNA
      and protein expression in pulmonary arteries. RESULTS: mPAP in H(4W), H(8W),
      SH(4W), SH(8W) group [(31 +/- 7), (32 +/- 8), (32 +/- 9), (31 +/- 10) mm Hg, 1 mm
      Hg = 0.133 kPa] were higher than that in C group [(14 +/- 4) mm Hg, all P <
      0.01], but mPAP in S(4W) and S(8W) group [(15 +/- 5), (16 +/- 6) mm Hg] were not
      increased (all P > 0.05). In S(4W), S(8W), H(4W), H(8W), SH(4W) and SH(8W) group,
      RVHI (0.258 +/- 0.024, 0.394 +/- 0.021, 0.374 +/- 0.020, 0.414 +/- 0.019, 0.434
      +/- 0.023, 0.442 +/- 0.020, respectively), the percentage of muscularized
      arteries [(33.5 +/- 6.8)%, (41.1 +/- 9.8)%, (35.9 +/- 6.6)%, (46.0 +/- 6.3)%,
      (42.9 +/- 6.5)%, (50.2 +/- 9.9)%, respectively] and alpha-SM-actin expression (53
      +/- 15, 75 +/- 14, 56 +/- 11, 82 +/- 17, 83 +/- 17, 98 +/- 16, respectively) were
      increased significantly (all P < 0.01). PASMC apoptosis was increased and
      proliferation was markedly increased. Apoptotic indices (AI, 2.5 +/- 1.0, 3.8 +/-
      1.4, 2.3 +/- 1.1, 3.3 +/- 1.1, 3.5 +/- 1.4, 4.8 +/- 1.4, respectively) and
      proliferation indices (PI, 33.1 +/- 11.8, 43.8 +/- 11.0, 36.5 +/- 10.6, 46.3 +/-
      12.1, 45.3 +/- 12.4, 53.3 +/- 13.4, respectively) were higher than those in C
      group (all P < 0.01). The expressions of PKC-alpha mRNA and protein were higher
      than those of C group (all P < 0.01). The differences were more significant
      between SH(4W) and H(4W) group, SH(8W) and H(8W) group (all P < 0.01).
      CONCLUSIONS: It is suggested that smoke is synergistic with hypoxia in
      aggravating pulmonary vascular remodeling. The possible mechanism is through PKC
      signaling transduction pathway activation.

PMID- 16409784
TI  - [A prospective study of clinical characteristics of fever after flexible
      fiberoptic bronchoscopy].
AB  - OBJECTIVE: To assess the incidence and clinical characteristics of fever after
      fiberoptic bronchoscopy (FOB). METHODS: Between May 2004 and April 2005, the
      clinical characteristics of fever in immunocompetent and hospitalized patients
      undergoing FOB were prospectively studied. RESULTS: One hundred and seventy-two
      hospitalized patients underwent FOB in this period, and 37 cases (22%) developed
      fever following FOB; in 32 (19%) the fever subsided within 24 h with a mean fever
      onset time of (3.5 +/- 1.7) h and mean fever duration of (10.8 +/- 6.7) h. There
      were significant increases in total leukocyte and neutrophil counts in the
      peripheral blood at 6 h after FOB compared to levels prior to FOB (all P < 0.01),
      but the numbers of leukocytes and neutrophils in patients with fever were
      significantly higher than those in patients without fever (all P < 0.01).
      CONCLUSIONS: Fever after FOB occurs relatively frequently but transiently in
      immunocompetent adults. No special treatment is needed.

PMID- 16409785
TI  - [The prevalence of obstructive sleep apnea-hypopnea syndrome in adults aged over
      20 years in Changchun city].
AB  - OBJECTIVE: To investigate the prevalence of obstructive sleep apnea-hypopnea
      syndrome (OSAHS) in adults aged over 20 years in Changchun city, providing
      epidemiological data for treatment and prevention of the disease. METHODS: 3,960
      subjects were derived from a stratified cluster and random sampling of the
      population in two districts of Changchun city. They were asked to answer the
      questions from a questionnaire in their houses. According to the degree of
      snoring, 200 subjects with a snoring score >or= 2 degree were selected to undergo
      polysomnography for a whole night and the prevalence of the disease was
      estimated. RESULTS: A total of 3,648 (97.64%) validated questionnaires was
      collected. Of them 31.00% had a snoring score >or= 2 degree, the prevalence was
      higher in males (40.07%) than in females (21.76%). The prevalence of snoring was
      higher in drivers (42.47%) than in other occupations. The estimated prevalence of
      OSAHS defined by apnea-hypopnea index (AHI) >or= 5, Epworth sleepiness scale
      (ESS) >or= 9 and arterial oxygen saturation (SaO(2)) < 90% was 4.81%.
      CONCLUSIONS: The estimated prevalence of OSAHS in adults aged over 20 years in
      Changchun city was 4.81%. Doctors should pay more attention to the disease and
      the ordinary people should be informed of the health impact of snoring and OSAHS.

PMID- 16409786
TI  - [Gene transfection of Livin isoforms into A549 cell line and its effect on cell
      growth and sensitivity to chemotherapy and radiotherapy].
AB  - OBJECTIVE: To express Livin alpha & beta in A549 cells by using gene
      transfection, and to observe its effect on cell growth and cell sensitivity to
      chemotherapy drugs and radiation. METHODS: Eukaryotic expression vectors of Livin
      alpha & beta were transfected into A549 cells and cell clones with stable
      expression were obtained. Livin alpha & beta expression levels in the transfected
      A549 cells were assessed at mRNA level and protein level, respectively. Cell
      growth status was assessed by biological features. MTT was performed to test
      effects of Livin on sensitivity of the A549 cells to chemotherapy drugs and
      radiation, and cell cycle analysis was performed to evaluate cell apoptosis.
      RESULTS: After transfection, positive cells, especially A549 cells expressing
      Livin, showed an increase of about 20% in colony-forming ability, a shorter
      doubling time (P < 0.05) and lower sensitivity to chemotherapy drugs and
      radiation (P < 0.01). Only 0.2% of the cells committed apoptosis with 10 Gy
      radiation. CONCLUSION: Livin isoforms, especially Livin alpha, are implicated in
      genesis and development of lung cancer, thus may be an important mechanism for
      drug resistance of lung cancer cells.

PMID- 16409787
TI  - [Polymerase chain reaction-single strand conformation polymorphism analysis
      combined with nucleic acid hybridization to detect ofloxacin-resistant
      Mycobacterium tuberculosis mutation selected in vitro].
AB  - OBJECTIVE: To explore the feasibility of utilizing polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP) analysis combined with
      Southern blot to detect ofloxacin (OFLX)-resistant Mycobacterium tuberculosis,
      and figure out the boundary between the OFLX-susceptible and resistant
      Mycobacterium tuberculosis. METHODS: OFLX-resistant Mycobacterium tuberculosis
      bacilli were induced in vitro and their minimal inhibitory concentration (MIC)
      and the minimal bactericidal concentration (MBC) were determined. The 320 bp
      segments of gyrA gene were amplified by PCR and their polymorphism was tested by
      SSCP from H(37)Rv, H(37)Ra and those induced OFLX-resistant strains. To prove the
      repeatability of PCR-SSCP combined with Southern blot, 36 clinical isolated OFLX
      resistant strains were tested. RESULTS: All of the 85 OFLX-resistant mutations
      involved in this study were identified to have gyrA mutations. The results showed
      that there was an overlap if OFLX 10 microg/ml was used as a criteria for
      discriminating susceptible and resistant strains. Compared with the H(37)Ra, the
      similar single-stranded shift caused by the single-stranded conformation change
      was viewed in the 36 clinical isolated OFLX-resistant strains by PCR-SSCP
      combined with Southern hybridization. CONCLUSIONS: PCR-SSCP analysis combined
      with Southern blot can clearly distinguish OFLX-susceptible from OFLX-resistant
      strains. The results suggest that as a cut-off point between OFLX-susceptible and
      low-level OFLX-resistant to Mycobacterium tuberculosis, OFLX concentration of 10
      microg/ml is considered to be a better one.

PMID- 16409791
TI  - [The role of regulatory T lymphocytes in asthma].

PMID- 16409808
TI  - [Treatment choices of fresh fractures of femoral neck in the elderly].

PMID- 16409788
TI  - [Molecular cloning, expression, purification and properties of isocitrate lyase
      gene from Mycobacterium tuberculosis H37Rv].
AB  - OBJECTIVE: To obtain recombinant protein with enzymatic activities of isocitrate
      lyase (ICL). METHODS: The icl gene was amplified by polymerase chain reaction
      (PCR) from Mycobacterium tuberculosis H(37)Rv strain genomic DNA and cloned into
      pET28-a(+) vector. The recombinant protein was expressed in E.coli BL21 (DE3).
      Enzyme activity of the protein was assayed after purifying with Ni-NTA resin.
      RESULTS: The recombinant ICL was purified in a highly active state with a
      specific activity of about 7.657 x 10(2) micromol x mg(-1) x min(-1). The pH
      curve indicated that recombinant ICL activity was optimal at pH 7.4. The LC/MS
      spectrometry showed a 50 603.347 molecular mass of recombinant ICL. The CD
      spectrum showed that the percentages for alpha- helix, beta- sheet, beta- turn,
      and random coil were 43.8%, 31.9%, 3.4%, and 20.9%, respectively. CONCLUSIONS:
      The icl gene of Mycobacterium tuberculosis H(37)Rv was successfully cloned and
      expressed. The enzymatic properties demonstrated the purified recombinant protein
      had activities of ICL. This work can facilitate immunologic research and the
      discovery of novel antimicrobial agents against Mycobacterium tuberculosis.

PMID- 16409809
TI  - [Hip joint replacement--an effective treatment of fractures of femoral neck in
      the elderly].

PMID- 16409811
TI  - [Principle of the classification of fractures of femoral neck in the elderly].

PMID- 16409810
TI  - [Discussion of non-displaced fractures of the femoral neck in the elderly].

PMID- 16409813
TI  - [Strategy for treatment of peritrochanteric fractures in senile patients].
AB  - OBJECTIVE: To analyze the clinical manifestations, operative applications,
      complications and outcomes of peritrochanteric fracture of femur in patients 75
      years old and over. METHODS: The clinical data of 261 patients, aged 79.5 (75
      96), of peritrochanteric fracture (265 hips) were analyzed. RESULTS: The
      incidence of different accompanied medical diseases was 2.6/person on average.
      The internal fixation methods included DHS, DHS plus trochanteric steady plate or
      intramedullary interlocking nails, such as Gamma nail, PFN and reconstructive
      nails. The mean operation time was 73 minutes. 224 cases were followed-up over 6
      months after operation 81% of which got excellent or good results. The
      complications included acute heart failure, brain infarction, cerebral
      thrombosis, pulmonary embolism, deep venous thrombosis of lower extremities, lung
      infection, and stress ulceration, bed sore, and acute respiratory failure.
      Thirteen cases died of cardiopulmonary insufficiency, cardiac infarction, brain
      thrombosis, or pulmonary embolism. CONCLUSION: Complications are frequent in aged
      patients. Appropriate operative methods help reduce complications and mortality
      rates.

PMID- 16409814
TI  - [Related factor analysis of avascular necrosis of the femoral head after internal
      fixation with cannulated screws in femoral neck fractures].
AB  - OBJECTIVE: To observe the accident of avascular necrosis of the femoral head
      after internal fixation with cannulated screws in femoral neck fractures and
      analysis of the related factors. METHODS: 212 cases of femoral neck fracture
      treated with cannulated screws between Sep. 1989 and Dec. 1999 were reviewed
      retrospectively. The average age was 45.2 years old, ranging from 13 to 70 years.
      Among the fractures, 3 were Garden stage I, 32 were Garden stage II, 107 were
      Garden stage III, 53 were Garden stage IV, and 17 unclassified. Average duration
      of follow-up was 32.7 months, ranging from 12 to 101 months. RESULTS: Fracture
      healing occurred in 203 cases (95.8%). Avascular necrosis of the femoral head
      occurred in 70 cases (33.0%) and late collapse developed in 30 cases (14.3%). The
      rate of the avascular necrosis and late collapse of the femoral head according to
      the Garden stage was 0/0, Garden stage I; 6.3%/0, Garden stage II; 33.6%/15.9%,
      Garden stage III; 49.1%/20.8%, Garden stage IV. Avascular necroses of the femoral
      head were observed within 3 years in most cases (95.7%). Correlation analysis
      shows Garden stage of the fracture was the major factor contributed to the
      accident of avascular necrosis and late collapse of the femoral head. It also
      shows the low risk of avascular necrosis and late collapse of the femoral head
      was related to the patient's age over 60; time of surgery within 14 days and
      Garden's reduction index within 155-180 degrees on both AP and Lateral views.
      CONCLUSION: Garden stage of the fracture is the major factor contributed to the
      accident of avascular necrosis and late collapse of the femoral head, emergency
      operation and good reduction is beneficial to reduce the accident of avascular
      necrosis of femoral head.

PMID- 16409815
TI  - [Clinical research of hemiprosthesis arthroplasty for the treatment of unstable
      intertrochanteric fractures in elderly patients].
AB  - OBJECTIVE: To report the clinical results of hemiprosthesis for unstable
      intertrochanteric fractures in elderly patients. METHODS: 86 cases (male 35 and
      females 51) of unstable intertrochanteric fractures in elderly patients were
      treated with hemiprosthesis arthroplasty in our hospital. The average age was 87
      years old (range from 80 to 98 years old). According to the Evans classification
      of intertrochanteric fractures, there were 31 cases in type IIIA, 35 cases in
      IIIB and 20 cases in type IV. Most of the patients fell in the room and
      fractured, with concomitant diseases. After admitted to the hospital, the
      patients were consulted and treated for the concomitant diseases, and after the
      general conditions got stable and no absolute contraindications were found, the
      hemiprosthesis arthroplasty was performed. Almost all of the patients were
      operated on within 3 days with general anesthesia under the multi-function
      monitoring. The greater trochanter was reconstructed with figure of 8 wire
      fixation, the lesser trochanter with figure of 8 wire fixation, the lesser
      trochanter was fixed with circular wire around proximal femur. The defect within
      the femoral calcar was filled with bone cement and in a part of the patients, the
      intertrochanteric fracture was transformed into femoral neck fracture and the
      femoral calcar was fixed with femoral prosthesis stem. RESULTS: All operations
      were successful and the duration of the operation was 45 to 70 minutes with an
      average of 55 minutes. Blood was transfused in 73 patients during the operation
      between 400-800 ml with an average 450 ml. The patients got out of the bed within
      3 days in 33 cases, 4-7 days in 43 cases, more than 8 days in 8 cases, and 2
      patients couldn't get out of the bed. The period of hospitalization was between
      13 to 27 days with an average of 16.8 days. COMPLICATIONS: 2 patients got slight
      deep phlebitis, 5 patients showed psychological disorders, and disorders in
      bacterial spectrum appeared in 3 patients, and after appropriate treatments, the
      complications gradually recovered and had no effect on the function of the
      affected extremity. 2 cases died of multiple organ failure during the
      hospitalization. 59 patients were followed up for 6 to 48 months with an average
      16 months. The result was excellent in 17 cases who resumed their activities as
      before they got fractured, good in 35 cases who could walk with walking aid, fair
      in 5 cases who could walk with others help, and poor in 2 cases who could not
      walk. 1 patient died of other diseases 5 months after discharged. No dislocation,
      loosening or late infections occurred. 88.1% showed excellent or good result.
      CONCLUSION: It's an effective method to treat the unstable intertrochanteric
      fractures in elderly patients with hemiprosthesis arthroplasty. The result was
      satisfactory. It can decrease the complications, reduce the mortality, improve
      the patient's the living quality, and reduce the burden of the patient's family.

PMID- 16409816
TI  - [Outcome of hip fractures after traction treatment in elderly].
AB  - OBJECTIVE: To observe the outcome of hip fractures which accepted traction
      treatment instead of operation considering their general condition in elderly.
      METHODS: 102 cases of hip fractures accompanied by heart disease, hypertension,
      diabetes etc from Nov. 2000 to Jan. 2005 were accepted traction treatment. Among
      them, 37 cases are femoral neck and 65 cases are femoral intertrochanteric
      fractures. The average age was 75.8 years old, ranging from 48 to 98 years old.
      All cases were treated at home. RESULTS: one-year mortality was 8.8% (9/102).
      According to the incidence, the complications include bedsore (30/102, 29.4),
      pulmonary infection (6/102, 5.9%), DVT (2/102), PE (1/102), Urine infection
      (1/102). The rate of healing in femoral neck fractures was 51.7% (15/29); in
      intertrochanteric fractures was 97.6% (40/41). The decrease of Harris score
      between pre-injury and post-injury was 23.1 in femoral neck fractures and 15.6 in
      intertrochanteric fractures. CONCLUSION: For non-displacement and stable femoral
      neck fractures and some intertrochanteric fractures, good results could be
      obtained by traction treatment. Considering its low cost, traction treatment had
      its own indications.

PMID- 16409817
TI  - [Clinical features, hormonal profile, and metabolic abnormalities of obese women
      with obese polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate and analyze the clinical presentation, hormonal
      profile, and metabolic abnormalities of obese women with polycystic ovary
      syndrome (PCOS). METHODS: The data of the anthropometric measurements, clinical
      manifestations of hyperandrogenism, serum levels of luteinizing hormone (LH),
      follicle stimulating hormone (FSH), estradiol (E(2)), testosterone (T), prolactin
      (PRL), dehydro-epiandrosterone sulfate (DHEAS), sex-hormone-binding globulin
      (SGBG), and 17-oxyhydroprogesterone (17-OHP), fasting plasma glucose (FPG) and
      fasting insulin (FINS) detected after oral glucose tolerance test (OGTT), serum
      lipid levels, including total cholesterol (Chol), triglycerides (TG), high
      density lipoprotein (HDL), and low-density lipoprotein (LDL), homeostasis model
      assessment (HOMA) and area under curve (AUC) so as to assess the insulin
      resistance (IR), free androgen index (FAI) to estimate the extent of
      hyperandrogenism, HOMA IS and DeltaI(30)/DeltaG(30) used to assess the function
      of islet beta cells, were collected from 192 women with PCOS, aged 24 +/- 6, that
      were divided into 2 groups according to the body mass index (BMI): Group A (n =
      70) with the BMI > or = 25 kg.m(-2) and Group B (n = 122) with the BMI < 2 5
      kg.m(-2), and 65 age-matched bilateral tubal block factor infertile women served
      as controls that were divided into 2 groups as well: Group C (n = 25) with the
      BMI > or = 25 kg.m(-2); and Group D (n = 79) with the BMI < 25 kg.m(-2), and
      underwent a cross-sectional study. RESULTS: (1) Clinical phenotype: The presence
      of obesity was 36.46% (70/192) of which 80.00% (56/70) was central obesity. The
      incidence of acanthosis nigricans was 17.18% (33/192), 35.71% in Group A and
      6.56% in Group B. (P < 0.01). Groups A and C showed increased frequency of
      acanthosis nigricans compared with Group B. The value of FAI of Group A was 3.40
      +/- 1.84, significantly higher than those of Group B (1.75 +/- 1.20) and Group C
      (1.65 +/- 0.90), (both P < 0.01). The LH/FSH ratio of Group B was 2.41 +/- 1.13,
      significantly higher than those of Groups A, C, and D (all P < 0.01). (2)
      Hormonal profile: The IR rate was 43.23% in the 192 patients, 82.86% in Group A
      and 20.49% in Group B. The LH and LH/FSH ratio were significantly higher in Group
      B than in Groups A, C, and D (all P < 0.01); T level was higher in Groups A and B
      than in Group C and D (all P < 0.05). SHBG was lower in Group A (108.70 +/- 81.35
      nmol.L(-1)) and Group C (150.34 +/- 106.23 nmol.L(-1)) compared with Group B
      (192.49 +/- 98.30 nmol.L(-1)) and Group D (231.84 +/- 90.09 nmol.L(-1)) (P < 0.01
      and P < 0.05). FAI level was 3.40 +/- 1.84 in Group A, significantly higher than
      those of Groups B (1.75 +/- 1.20), C (1.65 +/- 0.90), and D (0.84 +/- 0.45) (all
      P < 0.01). The FINS, TG, and HOMA IR of Groups A and C were all significantly
      higher than those of Groups B and D (all P < 0.01). The OGTT GAUC was
      significantly higher than those of Groups B, C, and D (P = 0.006, 0.028, and
      0.031 respectively). (3) Metabolic profile: The prevalence of IR was 43.23%
      (83/192) with a higher prevalence rate in Group A (82.76%, 58/70) compared with
      Group B (20.49%, 25/122). The values of FINS, HOMA IR, GAUC, IAUC, and TG were
      all higher in Group A than in Group B (all P < 0.01). BMI and WHR were positively
      correlated with FAI and HOMA-IR (all P < 0.01), whereas negatively correlated
      with LH/FSH ratio (r = -0.345, -0.260, P < 0.01). There were no significant
      differences in HOMA-IS and DeltaI(30)/DeltaG(30) among these groups (all P >
      0.05). CONCLUSION: Obese PCOS women have more severe hyperandrogenism, IR and
      hyperinsulinism than normal-weight PCOS women, which may have some health
      implications later in life.

PMID- 16409819
TI  - [Relationship between MDR1 gene polymorphism and blood concentration of
      tacrolimus in renal transplant patients].
AB  - OBJECTIVE: To investigate the relationship between MDR1 exon 21 and exon 26
      polymorphism and whole blood concentration of tacrolimus (FK506) in renal
      transplant patients. METHODS: Blood samples were collected from 86 renal
      transplant patients who received FK506 peri-operationally. PCR-RELP was used to
      determine the MDR1 genotype. The patients were divided into 3 subgroups for every
      position: GG, GT, and TT in exon 21; and CC, CT, and TT in exon 26. Three, six,
      and twelve months after the transplantation ELISA was used to measure the whole
      blood concentration of FK506. The FK506 concentrations standardized by dosage and
      body weight (FK506 concentration per dose/kg) were compared among the 3 subgroups
      within the MDR1 exon 21 and exon 26 groups. RESULTS: Of the 86 patients 26
      (30.2%), 35 (40.7%), and 25 (29.1%) were carriers of GG, GT, and TT in exon 21,
      and 26 (30.2%), 35 (40.7%), and 23 (26.8%) were carriers of CC, CT, and TT in
      exon 26. MDR1 exon 26 C3435T was in significant linkage disequilibrium with MDR1
      exon 21 G2677T. Three, six, and twelve months after the transplantation a
      significant correlation between the whole blood FK506 concentration per dose/day
      and MDR1 exon 21 and exon 26 genotypes. For exon 21 there were significant
      differences among the 3 subgroups (all P < 0.01). The ratio for the patients with
      GG was remarkably lower than that of those with GT and TT, and the ratio with GT
      was also lower than the patients with TT (P < 0.05). For exon 26, there was also
      a significant difference among the 3 subgroups (all P < 0.01). The ratio for the
      patients with CC was remarkably lower than those of the patients with CT and TT,
      and the ratio of CT was also lower than that of TT (P < 0.05). CONCLUSIONS: The
      MDR1 gene polymorphism is correlated with the whole blood concentration of FK506.
      To obtain the similar blood concentration of FK506, the patients with GG and CC
      should take the drug at a higher dose than those with Ct and TT.

PMID- 16409818
TI  - [Prevalence of antiepithelial cell antibody in systemic vasculitis and
      identification of the target antigen thereof].
AB  - OBJECTIVE: To investigate the prevalence of antiepithelial cell antibody (AECA)
      in systemic vasculitis (SV) and the target antigen thereof. METHOD: Sera of 113
      patients with SV of different kinds, 46 patients with Behcet's disease, 23
      patients with Takayasu arteritis, 19 patients with Wegener's granulomatosis, 8
      patients with polyarteritis nodosa, 7 patients with microscopic polyangiitis, and
      10 patients with Churg-Strauss syndrome were collected to detect the protein
      expression of AECA by Western blotting, with the protein of the endothelial cells
      of the line EA. hy926 line as substrate. Two-dimensional electrophoresis combined
      with immunoblotting, liquid chromatography-electrospray ionization mass
      spectrography was used to detect the target antigens related to vasculitis. Sera
      of 57 patients with systemic lupus erythematosus (SLE), 25 patients with
      rheumatoid arthritis (RA), and 20 healthy persons were collected as controls.
      RESULTS: The AECA-positive rate of the SV patients was 69.0%, not significantly
      different from that of the SLE patients (66.7%), but significantly higher than
      those of the RA patients (6.7%, P < 0.01) and healthy persons (0, P < 0.01). The
      AECA from the SV patients reacted with the endothelial cell (EC) antigens with
      the molecular size of 26 to 125 kDa, and the AECA from the SLE patients reacted
      with the EC antigens with the molecular size of 15 to 97 kDa. The EC antigens
      with the molecular size of 47 kDa was commonly found in the sera of the AECA
      positive SV patients and SLE patients, however, was not found in the RA, and
      polymyositis-dermatomyositis patients. The EC protein reacted by 47 kDa protein
      was identified by proteomic techniques as alpha-enolase. CONCLUSION: A group of
      heterogeneous antibodies, AECA can be found frequently in patients with SV and
      SLA. AECA reacts against a common EC antigen, alpha-enolase.

PMID- 16409820
TI  - [Diazoxide preconditioning combined with subsequent hypothermia alleviates anoxia
      re-oxygenation injury: experiment with rat hippocampal neurons].
AB  - OBJECTIVE: To observe the alleviative effects of preconditioning with diazoxide
      (DZ), a mitochondrial ATP-sensitive potassium channel opener, combined with
      subsequent hypothermia on anoxia-re-oxygenation injury. METHODS: Hippocampal
      neurons of new-born SD rat were cultured. DZ of the concentration of 250
      micromol/L was added into the culture fluid. The group of preconditioned cultured
      neurons were re-divided into 4 subgroups to be treated by hypothermia of
      different levels: 37 degrees C, 34 degrees C, 30 degrees C, and 22 degrees C, and
      then were derived of oxygen for 4 hours. The group of neurons without addition of
      DZ was re-divided into 4 subgroup too to be exposed to different temperatures and
      then underwent anoxia-re-oxygenation as described above. Thus the experiment was
      performed on 8 subgroups in total. Twenty-four hours after re-oxygenation the
      neurons were stained with dimethyl sulfoxide and their levels of absorptivity
      were measured so as to calculate the survival rate. Modified thiobarbital method
      was used to detect the concentration of malondialdehyde (MDA) in the culture
      fluid. Fluorescence probe Fluo-3-AM was added to detect the Ca(2+) concentration
      in the neurons. RESULTS: The survival rates of the DZ-preconditioned neurons of
      the 22 degrees C, 30 degrees C, and 34 degrees C subgroups were (94 +/- 8)%, (73
      +/- 9)%, (67 +/- 8)% respectively, all significantly higher than that of the 37
      degrees C subgroup (57 +/- 6%, all P < 0.01), with significant differences
      between the 22 degrees C subgroup and the 30 degrees C and 34 degrees C subgroups
      (both P < 0.01). The survival rates of the non-DZ-preconditioned neurons of the
      22 degrees C, 30 degrees C, and 34 degrees C subgroups were 66 +/- 10%, 52 +/-
      910%, 48 +/- 9% respectively, all significantly higher than that of the 37
      degrees C subgroup (41% +/- 7%, all P < 0.01), with significant differences
      between the 22 degrees C subgroup and the 30 degrees C and 34 degrees C subgroups
      (both P < 0.01). The survival rates at different temperatures in the DZ
      preconditioned group were all significantly higher than those in the
      corresponding non-preconditioned subgroups (all P < 0.01). The MDA concentration
      in the culture fluid of the 22 degrees C subgroup was significantly lower than
      those of the 30 degrees C, 34 degrees C, and 37 degrees C subgroups in both the
      DZ-preconditioned and non-preconditioned groups (all P < 0.01). The MDA
      concentrations of the preconditioned subgroups at different temperatures were all
      significantly lower than those of the corresponding non-preconditioned subgroups
      (all P < 0.01). The fluorescent value of the intracellular Ca(2+) of the 22
      degrees C subgroup was significantly lower than those of the 30 degrees C, 34
      degrees C, and 37 degrees C subgroups in both the DZ-preconditioned and non
      preconditioned groups (all P < 0.01). The fluorescent value of the intracellular
      Ca(2+) of the preconditioned subgroups at different temperatures were all
      significantly lower than those of the corresponding non-preconditioned subgroups
      (all P < 0.01). CONCLUSION: Hypothermia alleviates the anoxia-re-oxygenation
      injury: DZ preconditioning enhances the neuroprotection by hypothermia.

PMID- 16409821
TI  - [Clinical feature of hippocampal lesion: report of 21 cases].
AB  - OBJECTIVE: To explore the clinical features of hippocampal lesions. METHODS: the
      clinical data of 21 patients with hippocampal lesions, 15 males and 6 females,
      aged 19 (8-42), with a duration of mesial temporal lobe epilepsy (MTLE),
      underwent resection of the anterior temporal lobe, amygdaloid nucleus, and
      hippocampus. The resected hippocampal tissues were examined pathologically.
      Before the operation 24-hour EEG and MRI scan were performed. The patients were
      followed up for 1-2 years. RESULTS: The clinical manifestations included complex
      partial seizure (11 cases), absence seizure (5 cases), tonic-clonic seizure (4
      cases), and simple partial seizure (1 case). EEG showed spike waves in 18
      patients. MRI scan showed full hippocampus and long T2 signal in 10 cases,
      enlarged temporal horn, hyperintense signal in T2, and decreased volume of
      hippocampus in 8 cases, long T1 and T2 signals and obvious space-occupying lesion
      in hippocampus in one case, and normal images in 2 cases. Pathological
      examination revealed sclerosis of hippocampus in 11 cases, astrocytoma in 6
      cases, paraganglioma in 1 case, embryonic tumor of neuroepithelial tissue in 1
      case, atypical hyperplasia in 1 case, and radiation necrosis in 1 case. Sixteen
      of the eighteen followed-up patients remained seizure-free. Statistical analysis
      demonstrated significant difference in MRI between hippocampal tumor and
      hippocampal sclerosis. CONCLUSION: MTLE patients with T2 signal and hippocampus
      larger than that of the contralateral side should be considered as with
      hippocampal tumor and as indication of operation.

PMID- 16409822
TI  - [Cigarette smoking coacervate up-regulates the expression of gamma
      glutamylcysteine synthetase in alveolar epithelial cells mediated by activator
      protein-1].
AB  - OBJECTIVE: To investigate the effects of cigarette smoking coacervate (CSC) on
      the expression and activation of gamma-glutamylcysteine synthetase (GCS), a rate
      limitating enzyme in the synthesis of glutathione (reduced form). METHODS: Rat
      alveolar epithelial cells of the line CCL149 were cultured and exposed to CSC of
      the concentrations of 10, 1, and 0.1 microg/ml for 1, 4, 8, 12, 24, and 48 hours
      respectively. RT-PCR was used to detect the mRNA expression of gamma-GCS, and
      Western blotting was used to detect the protein expression of gamma-GCS. CCL149
      cells were transfected with pGL3/gamma-GCS or blank pGL3 plasmid. The luciferase
      activity was examined Gel retardation assay was used to detect the binding level
      of activator protein (AP)-1 with the region of the GCLC promoter in CCL-149 cell.
      RESULTS: The gamma-GCS mRNA expression levels of the CCL149 cells exposed to CSC
      > 1 microg/ml for 12, 24, and 48 hours were significantly higher than that of the
      control group (all P < 0.05). The gamma-GCS protein expression levels of the
      CCL149 cells exposed to CSC > 1 microg/ml for 12, 24, and 48 hours were
      significantly higher than that of the control group (all P < 0.05). The gamma-GCS
      protein activity of the CCL149 cells treated with CSC of the concentrations of 10
      microg/ml and 1 microg/ml decreased 1, 4, and 8 hours after and then increased in
      comparison with the control group (all P < 0.05). The gamma-GCS protein activity
      levels of the CCL149 cells treated with CSC of the concentration of 0.1 microg/ml
      for less than 48 hours was not significantly different from those of the control
      group (all P > 0.05), and the gamma-GCS protein activity level of the CCL149
      cells treated with CSC of the concentration of 0.1 microg/ml for 48 hours was
      significantly higher than that of the control group (P < 0.05). The activity of
      the luciferase with the plasmids containing 5-flanking regulatory region of rat
      GCLC gene and the activity of gamma-GCS in the CCL149 cells significantly
      increased after stimulation of CSC for 12, 24 and 48 hours (all P < 0.05). The
      binding levels of AP-1 with the region of the GCLC promoter in the CCL149 cells
      treated with CSC for 12, 24, and 48 hours were significantly increased.
      CONCLUSION: CSC up-regulates the expression of gamma-GCS by activation of the
      redox-sensitive transcription factor AP-1.

PMID- 16409833
TI  - [The prostate specific antigen: what can we learn from the American experience?].

PMID- 16409835
TI  - [T cell repertoires correlate with pathogenesis of chronic idiopathic
      thrombocytopenic purpura].
AB  - OBJECTIVE: To determine the T lymphocytic clones that correlate with the
      pathogenesis of idiopathic thrombocytopenic purpura (ITP) by investigating
      complementarity determining region (CDR3) repertoires of T cell receptors (TCRs)
      beta chain variable region (BV). METHODS: Twenty-five patients with idiopathic
      thrombocytopenic purpura (including 15 patients with acute ITP and 10 patients
      with chronic ITP), twenty normal peoples and 20 normal umbilical cord blood
      samples were enrolled. Reverse transcription-polymerase chain reaction (RT-PCR)
      was used to amplify 24 subfamily genes of the TCR (BV from the peripheral blood
      lymphocytes (PBLs) of the ITP patients and normal controls, the implications
      underwent electrophoresis on denatured polyacrylamide sequencing gel,
      establishing a map of TCR BV CDR3 gene expressing repertoire. The bands that
      widened or disappeared of the TCR BV gene repertoire on the electrophoresis gel
      were used to analyze the variety of T cell clones in the cases of ITP. Comparing
      the sequences of TCR BV CDR3 gene repertoire in normal and abnormal T cell clones
      made it possible to understand the relationship between TCR BV gene and ITP.
      RESULTS: (1) In aITP, TCR BV CDR3 size distribution was similar to that of the
      normal controls and oligoclonality could be observed in 15 cases with an average
      value of 2.7 +/- 0.9 per person. Abnormal TCR BV CDR3 size distribution in aITP
      had little difference compared with that in the healthy controls (P = 0.179).
      There was no common expanded T cell clones in aITP, while abnormal TCR BV CDR3
      distribution could be observed significantly different between the cITP patients
      and healthy controls (P < 0.05), with oligoclonality at an average value of 7 +/-
      3 per person in 10 cases. Common clonal T cell expansions could be observed in
      BV8, BV13.1, BV14 and BV17 subfamilies. In 10 cITP patients, sequence could be
      read from 18 out of 20 dense and strong T cell clone bands on the map of TCR BV
      CDR3, which suggested that a dominant monoclonal T cell expanded in cITP. (2)
      Different patients shared a common or similar CDR3 encoded by the TCR BV gene of
      the expanded T cell clones. The same CDR3 was found in 2/4 expanded BV 17 T cell
      clones, with only 2 amino acids different in framework four (FR4). Two T cell
      clones had almost the same sequence of CDR3 of BV17 except for only four basepair
      differences in their full sequences. The full TCRBV gene sequences remained the
      same in 2 T cell clones for TCRBV8 and in other 2 T cell clones for TCRBV13.1 in
      cITP group. It showed that an expanded T cell clones with common function existed
      and could recognize common antigen in the body of patients with cITP. In
      analyzing the common motif in CDR3 of different cITP, three common motifs were
      found: GANVLTFGAG, E/DTQYFGPG and N (K) EQFFGPG, which were separately used in
      different TCRBVCDR3 of 18 expanded T cell clones. Among these motifs, TCRBV17 of
      3 T cell clones had common GANVLTFGAG; TCRBV of 4 T cell clones had common N (K)
      EQFFGPG; and TCRBV of 7 T cell clones had common E/DTQYFGPG. CONCLUSION: aITP has
      no significant T cell clones expanded, while cITP usually demonstrates some
      expanded abnormal oligoclones which may correlate with the pathogenesis of cITP.
      cITP patients share 3 common motifs for TCRBV CDR3, which is possibly related to
      recolonization of the similar autoantigens.

PMID- 16409836
TI  - [Clinical features and outcomes of hyperthyroidism patients positive in
      propylthiouracil-induced antineutrophil cytoplasmic antibody].
AB  - OBJECTIVE: To analyze the clinical features and outcomes of hyperthyroidism
      patients positive in propylthiouracil (PTU)-induced antineutrophil cytoplasmic
      antibody (ANCA). METHODS: The clinical data, including the clinical
      manifestations, treatment, and outcomes of 45 PTU-induced ANCA positive patients
      with hyperthyroidism were prospectively studied. RESULTS: Seventeen of the 45
      patients had clinically evident vasculitis and 28 of the 45 patients were not
      complicated by vasculitis. In the vasculitis group, 13 patients (76.5%) had renal
      involvement manifested by hematuria, proteinuria, and renal insufficiency. 7 of
      them (41.2%) had lung involvement and 6 of them had hemoptysis. Perinuclear ANCA
      (p-ANCA) was detected in all 17 patients and 16 of them (94.1%) were anti
      myeloperoxidase antibodies (MPO-ANCA) positive. PTU was discontinued in all 17
      patients and the treatment was switched over to methimazole (MMI) in 6 patients.
      Four patients with severe organ involvement received prednisone and
      immunosuppressant for 6 to 12 months. No relapse or death occurred during the
      follow-up period (8 to 60 months with a median of 30 months). All the 17 patients
      achieved clinical remission except for two that developed end stage renal disease
      due to late diagnosis. 27 of the 28 patients without vasculitis (96.4%) were p
      ANCA positive and 14 of them (50.0%) were MPO-ANCA positive. PTU treatment was
      discontinued in 24 patients and switched over to MMI treatment in 15 patients,
      and 4 patients continued to take low dose PTU. No vasculitis manifestation
      occurred during the follow-up period (3 to 36 months with a median of 20 months).
      However, the ANCA titer declined slowly in most patients in both groups.
      CONCLUSION: PTU treatment should be discontinued without delay in the PTU-induced
      ANCA positive patients with hyperthyroidism. Treatment can be switched over to
      MMI when necessary. Patients with severe organ involvement should receive
      prednisone and immunosuppressant. No vasculitis relapse is found during the
      follow-up after withdrawal of PTU. However, ANCA may keep positive for a long
      time.

PMID- 16409837
TI  - [Expression of placental growth factor and pigment epithelium-derived factor in
      non-small cell lung cancer and the prognostic significance thereof].
AB  - OBJECTIVE: To study the expression of placental growth factor (PlGF) and pigment
      epithelium-derived factor (PEDF) in non-small cell lung cancer, explore the
      possible role of these factors in the process of neovascular forming, and
      understand the predict function of these factors to verdict non-small cell lung
      cancer patients' prognosis. METHODS: Immunohistochemistry was used to detect the
      expression of PlGF and PEDF in 81 surgical specimens of non-small cell lung
      cancer from patients. CD31 immunohistochemical staining was used to measure the
      microvessel density (MVD) so as to investigate the microvessel forming status.
      The association of these two factors with MVD and their predictive function for
      the prognosis of non-small cell lung cancer were analyzed. RESULTS: The positive
      rates of PlGF and PEDF in the non-small cell lung cancer specimens were 43.2%
      (35/81) and 53.1% (43/81) respectively. There was a positive relationship between
      PlGF positive expression and MVD, and a negative relationship between PEDF
      positive expression and MVD. Furthermore, there was a negative correlation
      between PlGF and PEDF expression. PlGF was an independent prognostic factor in
      both univariate and multivariate analysis. CONCLUSION: PlGF and PEDF are
      expressed in non-small cell lung cancer. They are antagonistic to each other in
      the process of neovessels forming. PlGF plays a more important role in the
      progression of non-small cell lung cancer and prediction of its prognosis
      compared with PEDF.

PMID- 16409838
TI  - [Inducing hepatocellular carcinoma-specific cytotoxic T lymphocyte response using
      formed by fusion of FastDCs and allogeneic human hepatocellular carcinoma cells].
AB  - OBJECTIVE: To fuse human hepatocellular carcinoma (HCC) cells with mature
      monocyte-derived dendritic cells (FastDC) and to observe in vitro the function of
      the fused cells in stimulating autologous T cells proliferation and inducing HCC
      specific cytotoxic T lymphocyte (CTL) response. METHODS: CD14(+) cells were
      isolated and purified from the peripheral blood of a healthy HLA-A2 blood donor
      and cultured in fresh dendritic cell complete medium for 24 h, then
      proinflammatory mediators were supplemented for another 24 h, thus generating
      mature dendritic cell (FastDCs). The FastDCs were fused with human HCC cells of
      the line HCCLM3 to generate novel dendritoma. T cells were isolated from selected
      CD14(-) cells and then divided into 4 groups to be stimulated with dendritoma
      cells, DCs, HCCLM3 cells, and mixed DCs-HCCLM3 cells respectively for 96 hours.
      18 hours before the end of cultivation (3)H-TdR was added into the culture fluid.
      Scintillation counter was used to measure the cpm values. CD8(+)T cells were
      isolated from CD14(-) cells, and added with different stimulating cells radiated
      by (60)Co and IL-2, IL-6, and IL-7. The values of IFN-gamma in the supernatants
      of the culture fluid of CD8(+)T cells with dendritoma cells, DCs, HCCLM3 cells,
      and mixed DCs-HCCLM3 cells was measured. HCCLM3, K562, HLE, self monocytes
      labeled with Na(2)(51)CrO(4) were added with effector cells, gamma-scintillation
      counter was used to measure the cpm value so as to calculate the killing ability
      of CTL. RESULTS: The CTLs activated by dendritoma cells specifically killed the
      HCCLM3 cells in the context of MHC class I and acted less vigorously against the
      control target cells. The CTLs activated by dendritoma cells were stronger in
      killing HCCLM3 cells than DCs, HCCLM3 cells, and mixed DCs-HCCLM3 cells (all P <
      0.05). The killing activity was decreased on the HCCLM3 cells incubated with anti
      HLA-ABC antibody. Three, five, and seven days after co-cultivation the value of
      IFN-gamma in the supernatants of the culture fluid of CD8(+)T cells with fused
      cells, DCs, HCCLM3 cells, and mixed DCs-HCCLM3 cells increased gradually,
      especially in the supernatants of the culture fluid of CD8(+)T cells with
      dendritoma cells (400 pg/ml +/- 60 pg/ml 3 days after, 1030 pg/ml +/- 160 pg/ml 5
      days after, and 1260 pg/L +/- 180 pg/L 7 days after). CONCLUSION: The novel
      dendritomas formed with HCCLM3 cells and mature FastDCs from healthy human
      peripheral blood CD14(+) monocytes are potent stimulators for CD8(+)T cells in
      inducing HCCLM3 cell-specific lysis. With shorter time required for in vitro DC
      development, the rapid method of generation of dendritoma is more economic and
      may represent a new strategy for immunotherapy of hepatocellular carcinoma.

PMID- 16409839
TI  - [Influence of platelet activating factor and its antagonist on portal
      hypertension associated with liver cirrhosis: an experiment with rats].
AB  - OBJECTIVE: To investigate the influence of platelet activating factor (PAF) and
      its antagonist BN52021 on portal hypertension associated with liver cirrhosis.
      METHODS: Ten SD rats were injected intraperitoneally with carbon tetrachloride to
      establish a liver cirrhosis model and 10 rats were injected with olive oil as
      controls. The concentrations of PAF in the blood and liver was examined by rapid
      (3)H-PAF scintillation proximity assay and the hepatic PAF binding capacity was
      examined by receptor saturation binding technique. The pressure of portal vein
      and pressure of femoral artery were measured by intubation method. BN52021 was
      infused into the portal vein to observe its influence on the blood pressure.
      RESULTS: The hepatic PAF levels of the cirrhotic rats was 4.0 ng/g +/- 0.4 ng/g,
      significantly higher than that of the control rats (2.7 ng/g +/- 0.5 ng/g, P <
      0.01). The hepatic efflux PAF level of the cirrhotic rats was 6.3 ng/g +/- 0.6
      ng/g, significantly higher than that of the control rats (3.4 ng/g +/- 0.6 ng/g,
      P < 0.01). The hepatic output PAF levels of the cirrhotic rats was 1.0 ng/g +/-
      0.6 ng/g, significantly lower than that of the control rats (0.3 ng/g +/- 0.5
      ng/g, P < 0.01). The maximum PAF binding capacity of the cirrhotic rats was 2.8
      +/- 0.21 fmol/microg protein, significantly higher than that of the control rats
      (0.9 +/- 0.06 fmol/microg protein, P < 0.01). However, the receptor affinity was
      not significantly different between these 2 groups. The portal pressure of the
      cirrhotic rats was 12.2 mm Hg +/- 0.7 mm Hg, significantly higher than that of
      the control rats (5.3 mm Hg +/- 0.6 mm Hg, P < 0.01). The femoral arterial
      pressure of the cirrhotic rats was 82 mm Hg +/- 10 mm Hg, significantly lower
      than that of the control rats (114 mm Hg +/- 9 mm Hg, P < 0.01). Infusion of PAF
      via the portal vein increased the portal pressure from 12.1 mm Hg +/- 0.6 mm Hg
      with an increase of 32% (P < 0.01) in the cirrhotic rats, and from 7.7 mm Hg +/-
      0.8 mm Hg with an increase of 23%. The PAF response of the cirrhotic rats was 4.1
      mm Hg +/- 1.0 mm Hg (227%), significantly higher than that of the control rats
      (1.8 mm Hg +/- 0.3 mm Hg, P < 0.01). The femoral artery pressure decreased from
      82 mm Hg +/- 10 mm Hg to 48 mm Hg +/- 4 mm Hg (P < 0.01) in the cirrhotic rats,
      and from 114 mm Hg +/- 9 mm Hg to 52 mm Hg +/- 4 mm Hg (P < 0.01). After portal
      infusion of BN52021 the portal pressure decreased from 14.6 mm Hg +/- 1.6 mm Hg
      to 12.3 mm Hg +/- 0.8 mm Hg (P < 0.05) with a decrease of 16%, however, did not
      significantly influenced the femoral arterial pressure in the cirrhotic rats, and
      did not significantly influenced the portal pressure and femoral arterial
      pressure in the control rats. CONCLUSION: The increased hepatic PAF synthesis in
      cirrhotic is the major source of elevated circulating PAF It upregulates the
      hepatic hemodynamics that contributes to portal hypertension. The increased
      portal pressure by endogenous PAF can be decreased to a certain extent by BN52021
      which may be used in treatment of portal hypertension.

PMID- 16409841
TI  - [Granulocyte colony-stimulating factor-mobilized autologous bone marrow stem
      cells promote the liver regeneration of partial liver transplant: an experiment
      with rats].
AB  - OBJECTIVE: To investigate the effects of granulocyte colony-stimulating factor (G
      CSF)-mobilized autologous bone marrow stem cells on the liver regeneration of
      partial liver transplant. METHODS: A 50% partial liver transplantation model as
      established by transplanting parts of the liver of female rats to the male rats
      with the equal weights that had had parts of their livers resected. Then the
      transplanted male rats were randomly divided into 3 equal groups: G-CSF + PLTx
      group that was injected hypodermically with recombinant human G-CSF (rhG-CSF)
      daily for 5 days and then underwent liver resection and 50% partial liver
      transplantation (PLTx); PLTx + G-CSF group that underwent PLTx and 3 hours after
      the transplantation received injection of rhG-CSF daily for 5 days, and PLTx
      control group that underwent PLTx and 3 hours later received injection of normal
      saline daily for 5 days. One, 3, 5, 7, and 14 days after the PLTx blood samples
      and livers were collected from 6 rats from each group, and one hour before the
      liver was taken bromodeoxyuridine (BrdU) was injected intraperitoneally to be
      integrated into the synthesis of DNA in the liver cells. Immunohistochemistry was
      used to detect the CD34 and BrdU-positive cells. In situ hybridization was used
      to detect the sry (sex-determining region) gene so as to determine the origin of
      the proliferating cells in the transplanted liver. RESULTS: The 14-day survival
      rate of the G-CSF + PLTx group was 90%, significantly higher than those of the G
      CSF + PLTx (60%) and PLTx group (50%) (both P < 0.05) with a significant
      difference between the latter 2 groups too (P < 0.05). The mitosis index of liver
      cells 3 days after the transplantation of the PLTx + G-CSF group was 30% +/- 5%,
      significantly higher than those of the G-CSF + PLTx group (24% +/- 7%) and PLTx
      group (24% +/- 6%) (both P < 0.05) without a significant difference between the
      latter 2 groups. The rate of BrdU-positive cells of the PLTx + G-CSF group was
      42% +/- 6%, significantly higher than those of the G-CSF + PLTx group (38% +/-
      4%) and PLTx group (34% +/- 8%) (both P < 0.05). The transplantation the mitosis
      index and rate of BrdU-positive cells decreased since the 7th days after
      transplantation in all 3 groups, however, with the same relationship among them.
      The numbers of CD34(+) cell around the portal area of the 2 G-CSF groups
      increased since the 3rd day after transplantation in comparison with the PLTx
      group, was the highest on the 3rd day for the G-CSF + PLTx group, and continued
      to increase in the PLTx + G-CSF group. Since the 3rd day after transplantation,
      sry-positive cells were seen in the hepatic sinusoid and portal area in the 2 G
      CSF groups, and were rarely seen in the PLTx group. CONCLUSION: G-CSF treatment
      after 50% PLTx significantly promotes liver regeneration and ameliorates the
      liver damage, thus raising the survival rate.

PMID- 16409842
TI  - [Effects of immunotherapy with anti-L3T4 monoclonal antibody on autoimmune
      cardiomyopathy: experiment with mice].
AB  - OBJECTIVE: To evaluate the effects of immunotherapy with anti-L3T4 monoclonal
      antibody (McAb) on autoimmune cardiomyopathy. METHODS: 24 male Balb/c mice were
      immunized with mitochondria ADP/ATP carrier peptides so as to establish a model
      of autoimmune cardiomyopathy, and then randomly divided into 4 equal groups:
      cardiomyopathy control group, early-treated group injected with anti-L3T4 McAb on
      the day before immunization, the very day of immunization, and 1 day after the
      immunization, mid-term-treated group, administrated with anti-L3T4 McAb on the
      89th, 90th and 91st days after immunization, and sham-immunization control group,
      injected with solution without anti-L3T4 McAb. Six months after blood samples
      were collected. The serum antibodies against ADP/ATP carrier were examined with
      ELISA, and the expression of IFN-gamma and IL-4, T cell cytokines, in T cells
      were detected by 3-color flow cytometry. The myocardium underwent pathological
      examination by using light and electron microscopes. The bulk percentages of
      cardiac collagen fiber were calculated with computer. RESULTS: Antibodies against
      ADP/ATP carrier were negative in the early-treated group and the sham
      immunization control group and positive in the mid-term-treated and
      cardiomyopathy groups with a transient decline in the mid-term-treated group. By
      the end of 6 month, there were no cardiac morphological and histopathological
      changes like those in dilated cardiomyopathy (DCM) in the early-treated group and
      sham-immunization group, while they were found in the mid-term-treated and
      cardiomyopathy groups with severer myocardial impairments in the cardiomyopathy
      group. The percentage of IFN-gamma/IL-4 of the early-treated group was 6.56% +/-
      0.21%/2.54% +/- 0.20%, not significantly different from that of the control group
      (5.87% +/- 0.19%/2.16% +/- 0.10%), however, the values of these 2 groups were
      significantly higher than those of the mid-term-treated group (8.91% +/-
      0.33%/5.15% +/- 0.13%, both P < 0.01) and the cardiomyopathy group (7.85% +/-
      1.42%/9.45% +/- 1.70%, both P < 0.01). CONCLUSION: Anti-L3T4 McAb administration
      is effective on protection from autoimmune cardiomyopathy induced by mitochondria
      ADP/ATP carrier peptides, especially being used at the initial phase of this
      disease.

PMID- 16409843
TI  - [Mechanism of cardioprotection against ischemia/reperfusion injury by valsartan:
      an experiment with isolated rat hearts].
AB  - OBJECTIVE: To investigate the mechanism of protection of reperfused ischemic
      heart by valsartan. METHODS: The hearts of 40 SD rats were isolated, linked to
      Langendorff perfusion apparatus, and randomly divided into 5 equal groups:
      control group, to be perfused with modified Kreb-Henseleit (K-H) buffer for 110
      minutes; ischemia/reperfusion (I/R) group, to be perfused with K-H buffer for 20
      min, exposed to ischemia for 30 min, and then reperfused with K-H buffer for 60
      min; HOE140 group, to be perfused with K-H buffer with HOE140, a bradykinin
      beta(2) receptor antagonist for 20 min, exposed to ischemia for 30 min, and then
      reperfused with K-H buffer with HOE140for 60 min; valsartan group, perfused with
      K-H buffer with valsartan for 20 min, exposed to ischemia for 30 min, and then
      reperfused with K-H buffer with valsartan for 60 min; and valsartan + HOE140
      group, perfused with K-H buffer with valsartan + HOE140 for 20 min, exposed to
      ischemia for 30 min, and then reperfused with K-H buffer with valsartan + HOE140
      for 60 min. The left ventricular systolic pressure (LVSP) and maximal uprising
      velocity of left ventricular pressure (+dp/dt(max)) were measured 20 minutes
      after the stabilization of perfusion, and 20, 40, and 60 minutes after
      reperfusion. After the stop of reperfusion Evans blue was infused via the aorta
      and the no-flow area was measured. The MB isoenzyme of creatine kinase (CK-MB) in
      the effluent liquid from the heart was measured 20 minutes after the
      stabilization of perfusion, and 1, 30, and 60 minutes after reperfusion. RESULTS:
      The LVSP and +dp/dt(max) of the control group were significantly higher than the
      other 4 groups (all P < 0.01). The LVSP and +dp/dt(max) of the valsartan group
      were significantly higher than those of the I/R group (both P < 0.01). The LVSP
      and +dp/dtmax of the valsartan + HOE140 group were significantly lower than those
      of the valsartan group (P < 0.01 and P < 0.05). The no-flow area of the HOE140
      group was not significantly different from that of the I/R group (P > 0.05). The
      no-flow area of the valsartan group was significantly smaller than that of the
      I/R group, almost half of that of the latter (P < 0.01). The CK-MB levels after
      I/R at different time points were all significantly higher than that of the
      control group (all P < 0.01). The CK-MB levels of the HOE140 group were not
      significantly different from those of the I/R group (all P > 0.05). The CK-MB
      levels at different time-pints of the valsartan group were all significantly
      lower than those of the I/R group (all P < 0.01). The CK-MB levels at different
      time-pints of reperfusion of the valsartan + HOE140 group were all significantly
      higher than those of the valsartan group (all P < 0.05). Linear correlation
      analysis showed that the CK-MB level 60 minutes after reperfusion was positively
      correlated with the no-flow area with a correlation coefficient of 0.85 (P <
      0.01). CONCLUSION: Valsartan protects the heart from I/R injury partially by
      increasing the level of bradykinin. Bradykinin beta(2) receptor antagonist blunts
      the cardioprotective effect of valsartan.

PMID- 16409844
TI  - [Difference and significance of peripheral blood T-lymphocyte subsets in patients
      with chronic hepatitis B and asymptomatic HBV carriers].
AB  - OBJECTIVE: To investigate the difference of peripheral blood T-lymphocyte subsets
      in patients with chronic hepatitis B and asymptomatic HBV carriers, and to
      analyze the relationship between the pathogenesis of hepatitis B and the hosts'
      cellular immunity. METHODS: Flow cytometry was used to detect the peripheral
      blood T-lymphocyte subsets in 29 patients of chronic hepatitis B, 25 asymptomatic
      HBV carriers and 35 healthy blood donors. RESULTS: Compared with normal controls,
      the numbers of leucocytes, lymphocytes, T-lymphocytes, CD4+ T cells, CD8+ T
      cells, CD4+CD28+ T cells and CD8+CD28+ T cells decreased in both the patients
      with chronic hepatitis B and asymptomatic HBV carriers, the number of NK cells of
      the patients with chronic hepatitis B decreased as well. Compared with normal
      controls and asymptomatic HBV carriers, the proportions of CD8+CD38+ T cells and
      CD4+CD45RA-memory T cells markedly increased and the proportion and number of
      CD4+CD45RA+62L+ T cells decreased in patients with chronic hepatitis B.
      CONCLUSION: There is an imbalance in peripheral blood T-lymphocyte subsets and
      turbulence in cellular immunity in the patients with chronic hepatitis B and
      asymptomatic HBV carriers, which may be associated with HBV persistent infection.

PMID- 16409845
TI  - [Immediate breast reconstruction with DIEP flap following modified radical
      mastectomy].
AB  - OBJECTIVE: To review the experience in immediate breast reconstruction with DIEP
      flap following modified radical mastectomy. METHODS: From 2003 to 2005, eight
      patients with breast cancer have undergone modified radical mastectomy and
      immediate breast reconstruction with deep inferior epigastric perforator flap.
      Six patients had stage I disease and 2 patients had stage II disease. RESULTS:
      The flaps in all the cases survived. Two occurred minor complications. A small
      part of venous congestion occurred in one flap. One patient had hematoma under
      the flap. Follow up more than 6 months, no evidence of recurrence and metastasis
      occurs. Postoperative abdominal wall examination didn't reveal and hernia and
      bulging. Patient satisfaction with the reconstructed breast was rated high. The
      reconstructed breast achieved good results in shape, colour and symmetry.
      CONCLUSION: The procedure introduced is an ideal method for breast reconstruction
      after modified radical mastectomy.

PMID- 16409846
TI  - [Effect of surgical treatment of tricuspid regurgitation late after valve
      replacement of left heart].
AB  - OBJECTIVE: To investigate the appropriate methodology and outcome of surgical
      treatment of tricuspid regurgitation late after valve replacement of left heart.
      METHODS: Eighteen patients with tricuspid insufficiency, with the diagnosis
      conformed by echocardiogram and in New York Heart Association (NYHA) class III to
      IV, were treated surgically 3 to 14 years after left heart valve replacement,
      including 13 mitral valve replacements and 5 double valve replacements, from
      January 1995 to May 2004. DeVega was used in 5 patients. The ages at the time of
      tricuspid surgery ranged from 35 to 65 years (median 50 years). The patients were
      followed up for 36.7 months (12-114 months). RESULTS: There was no death from
      hemorrhage because of re-open. Tricuspid repair was performed in 8 patients,
      tricuspid replacement was done in 10 patients, 5 bioprostheses and 5 mechanical
      valves were implanted. The hospital mortality was 16.7%. Among the survivors, the
      three-year survival rate was 78.8%. Twelve patients showed improvement of
      symptoms, while there was no improvement in 3 patients who needed medical
      therapy. CONCLUSION: The pathophysiology of tricuspid regurgitation is associated
      with delayed left heart operation, implement of tricuspid repair in the first
      operation or progressive right ventricular failure. The surgical intervention
      should be earlier before the onset of severe right ventricular failure Tricuspid
      valve repair is the procedure of choice, while tricuspid valve replacement is
      also acceptable.

PMID- 16409856
TI  - [To carry forward the spirit of science criticism in medical research].

PMID- 16409848
TI  - [Therapeutic efficacy of bipolar plasmakinetic technique compared with
      transurethral resection on benign prostate hyperplasia].
AB  - OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with
      the bipolar plasmakinetic technique (PKRP) compared with the transurethral
      resection (TURP) in the treatment of benign prostate hyperplasia (BPH). METHOD:
      Four hundred BPH patients with matched lesions were divided into 2 groups: 200
      patients, aged 74.1 (58-91), underwent transurethral prostatectomy with PKRP, and
      200 patients, aged 73.8 (56-90), underwent TURP. RESULT: In the PKRP group the
      average IPSS decreased from 27.1 +/- 4.5 preoperatively to 11.3 +/- 3.4
      postoperatively 6 months after (P < 0.01), the. average maximum flow-rate Q (max)
      increased from 6.1 +/- 2.4 ml/s preoperatively to 18.6 +/- 3.5 ml/s
      postoperatively (P < 0.01), and the average residual urine (RU) reduced from
      102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P <
      0.01). However in the TURP group the average IPSS decreased from 26.9 +/- 4.2
      preoperatively to 10.8 +/- 3.6 6 months after the operation (P < 0.01), the Q
      (max) increased from 5.7 +/- 2.4 ml/s preoperatively to 19.1 +/- 3.7 ml/s
      postoperatively (P < 0.01), and the average RU decreased from 102.3 +/- 43.3 ml
      preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). There were no
      significant differences in these parameters between these 2 groups (all P >
      0.05). The average catheter retention time was 31.5 h in the PKRP, significantly
      shorter than that in the TURP group (61.5 hours, P < 0.01). The incidence rate of
      post-operational asynodia in the PKRP group was 14.3%, not significantly
      different from that in the TURP group (15.2%, P > 0.05). During the operation no
      hemorrhage or transurethral resection syndrome (TURS) occurred in the PKRP group,
      however, there were 5 cases of TURS and 18 cases of blood transfusion in the TURP
      group. CONCLUSION: PKRP has the same therapeutic efficacy as TURP on BPH.
      Moreover, it was more cheaper and with lower complication than TURP.

PMID- 16409857
TI  - [High risk factors of upper gastrointestinal bleeding after neurosurgical
      procedures].
AB  - OBJECTIVE: To analyze high risk factors of postoperative upper gastrointestinal
      (GI) bleeding after neurosurgery so as to give guidance for prevention of GI
      bleeding. METHODS: A questionnaire was developed to investigate the medical
      records of 1500 patients who were hospitalized and underwent neurosurgical
      operations in 1997. Logistic regression analysis was made. RESULTS: 1430 valid
      questionnaires were obtained. Postoperative upper GI bleeding occurred in 75
      patients (5.24%). The incidence of upper GI bleeding were 6.64% (54/813) in the
      male patients and 3.40% (21/617) in the female persons (P = 0.007); 9.88%
      (41/415) in those aged > 50 and 3.35% in those aged < or = 50 (P = 0.001).
      Glasgow Coma Score less than 10 pre- and post-operation, the incidence of upper
      GI bleeding was more than 17.5% (14/80, pre-operation GCS 7-10) and 20.9% (14/67,
      pre-operation GCS 3-6), and 20.25% (16/79, first day of post-operation GCS 7-10)
      and 23.75% (19/80, first day of post-operation GCS 3-6). The incidence of upper
      GI bleeding of the patients with intracerebral hematoma, intraventricular
      hemorrhage, subdural hematoma, and extradural hematoma were 15.7%, 10.0%, 6.00%,
      and 2.94% respectively (P = 0.02). The incidence of upper GI bleeding of the
      patients with tumors of fourth ventricle of cerebrum, brainstem, cerebral
      hemisphere, and sellar hypothalamus were 15.79% (3/19), 7.89%, 5.71%, and 3.74%
      respectively. In the emergent cases, the incidence of upper GI bleeding was
      higher in those with hypertension. The incidence of upper GI bleeding was 5.46%
      in the patients undergoing adrenocortical hormone treatment, significantly higher
      than that in those who did not receive such treatment (2.13%). CONCLUSION:
      Patients who are at high risk of developing postoperative upper GI bleeding
      including that: age greater than 50 years; male; Glasgow Coma Score less than 10
      pre and post operation; The lesion was located in brain stem and forth ventricle;
      Hypertensive cerebral hemorrhage; Intracerebral and intraventricular hemorrhagic
      brain trauma; Postoperative pneumonia, brain edema, encephalic high pressure,
      pyogenic infection of the central nervous system and other postoperative
      complications. The mortality of patients with postoperative upper GI bleeding was
      evidently higher than that of the patients without postoperative upper GI
      bleeding.

PMID- 16409858
TI  - [Pleuropulmonary manifestations of systemic lupus erythematosus].
AB  - OBJECTIVE: To analyze the incidence, clinical features, and prognosis of
      pleuropulmonary involvement in patients with systemic lupus erythematosus (SLE).
      METHODS: The medical records of 320 SLE inpatients hospitalized in Peking Union
      Medical College Hospital 2004, 50 males and 270 females, aged 33 +/- 14 (8-75),
      were retrospectively analyzed. RESULTS: Pleuropulmonary involvement occurred in
      142 cases with an incidence rate of 44.4%. The incidence of pleural involvement
      was 25% (80/320) and the incidence of pulmonary parenchyma involvement was 33.8%
      (108/320). The mortality rate of the SLE patients with thoracic involvement was
      7.0%, significantly higher than that of the SLE patients without thoracic
      involvement (1.0%, P = 0.006). The incidence of acute lupus pneumonitis (ALP) was
      1.3% and the survival rate of ALP was 100%. The clinical manifestations of ALP
      included hypoxemia, dyspnea, fever, and cough and chest radiograph
      characteristically showed unilateral or bilateral patchy acinar infiltrates
      predominantly in the lower lung zone. The incidence of diffuse alveolar
      hemorrhage (DAH) was 1.9% with a mortality rate of 66.7%. The clinical
      manifestations of DAH included hemoptysis, hypoxemia, cough, anemia and bloody
      bronchoalveolar lavage and the chest radiographic findings included new acinar
      infiltrates that were typically diffuse and bilateral and might be patchy. The
      other common pleuropulmonary complications of SLE included pleural disease (25%),
      chronic interstitial pneumonitis (6.9%), pulmonary hypertension (15.3%),
      pulmonary embolism (1.9%), and pulmonary infection (19.1%). CONCLUSION: SLE may
      affect all components of the respiratory system. Thoracic involvement is an
      adverse prognostic sign. Life-threatening pulmonary involvement is not uncommon.
      The clinicoradiographic features of the SLE-associated pulmonary syndromes
      overlap. Aggressive diagnostic evaluations such as blood culture, sputum culture,
      fibreoptic bronchoscopy, and lung biopsy are very important.

PMID- 16409859
TI  - [Microsatellite polymorphism of (tttta) n in the promoter of CYP11a gene in
      Chinese women with polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the distribution of (tttta) n microsatellite
      polymorphism in the promoter of CYP11a gene in Chinese women with polycystic
      ovary syndrome (PCOS) and the relationship between such polymorphism and PCOS.
      METHODS: Peripheral blood samples were obtained from 201 women with PCOS, aged 26
      +/- 4, and 147 women without PCOS, aged 29 +/- 5. Radioimmunoassay was used to
      examine the levels of testosterone, follicle-stimulating hormone, luteinizing
      hormone, progesterone, estradiol, and prolactin. Locus-specific prime PCR was
      used to detect the frequencies of the CYP11a alleles. Body mass index (BMI) was
      calculated. RESULTS: The average BMI of the women with PCOS was 22 kg/m(2) +/- 4
      kg/m(2), and that of the non-PCOS women was 22 kg/m(2) +/- 6 kg/m(2). The six
      repeat allele variant genotypic distribution of CYP11a was statistically
      different between the women with PCOS and those without PCOS [Fisher's exact test
      (2-tail), P = 0.031]. The frequency of 6//6 genotype in the PCOS patients was
      57.7% (116/201), significantly higher than that of the non-PCOS women [44.9%
      (66/147), chi(2) = 5.588, P = 0.018]. The BMI of the PCOS patients with 4//4
      genotype was 19.4 kg/m(2) +/- 1.7 kg/m(2), statistically lower than those of the
      PCOS patients with 4//6, 6//6, and 6//8 genotypes (23.6 kg/m(2) +/- 3.3 kg/m(2),
      22.5 kg/m(2) +/- 3.8 kg/m(2), 22.2 kg/m(2) +/- 4.2 kg/m(2) respectively, P =
      0.0037, 0.0027, and 0.059 respectively). The PCOS patients with the allele
      (tttta) 6 had markedly higher BMI (22.7 kg/m(2) +/- 3.7 kg/m(2)) than those
      without the allele (tttta) 6 (19.4 kg/m(2) +/- 1.7 kg/m(2), P = 0.0075). No
      differences were observed in the serum levels of reproductive hormones among the
      individuals with different genotypic features in the PCOS patients. CONCLUSION:
      The six-repeat allele is the most common fragment of (tttta) n microsatellite
      polymorphism in Chinese Han woman. The 6//6 genotype is significantly more
      frequent and is associated with greater BMI in the women with PCOS. The six
      repeat allele variant may play a certain role in the pathogenesis of PCOS.

PMID- 16409860
TI  - [Effects of lidocaine on brain damage induced by transient global cerebral
      ischemia in mice of different apolipoprotein E genotypes].
AB  - OBJECTIVE: To evaluate the effects of lidocaine on changes of neuropathological
      outcome as well as the learning and memory abilities induced by transient global
      cerebral ischemia in mice of different apolipoprotein E genotypes. METHODS:
      Transient global ischemia was induced by bilateral common carotid arteries
      occlusion (BCCAO) for a period of 17 minutes. Healthy male C57BL/6J wild-type
      mice (C57 mice) and apolipoprotein E knockout mice (apoE mice) were randomly
      divided into six groups: C57 control group (n = 15, undergoing sham operation,
      neither BCCAO was performed nor pharmacologic intervention was given), C57
      ischemia group (n = 21, BCCAO for 17 minutes was performed and normal saline was
      given intraperitoneally), C57 lidocaine group (n = 22, BCCAO for 17 minutes was
      performed and lidocaine was given intraperitoneally), apoE control group (n = 15,
      undergoing the same procedure as that of the C57 control group), apoE ischemia
      group (n = 19, undergoing the same procedure as that of the C57 ischemia group),
      apoE lidocaine group (n = 16, undergoing the same procedure as that of the C57
      lidocaine group). The mice were allowed to recover for 7 days. Twenty-eight mice
      were randomly selected from these 6 groups for neuropathological studies on the 7
      th postoperative day. The percentage of ischemic neurons in the CA1 region of
      hippocampus was calculated. Morris water maze tasks were performed for the rest
      mice from the 8 th postoperative day. Mice were tested four times daily for 5
      consecutive days. The latency period was recorded and the percentage of effective
      search strategies were calculated. RESULTS: (1) The percentage of ischemic
      neurons in the CA1 region of hippocampus was 0.3% +/- 0.1% in the C57 control
      group, 19.3% +/- 4.5% in the C57 ischemia group, 36.9% +/- 2.5% in the C57
      lidocaine group, 0.6% +/- 0.3% in the apoE control group, 65.5% +/- 2.2% in the
      apoE ischemia group, and 39.4% +/- 6.5% in the apoE lidocaine group,
      significantly higher in the ischemia and lidocaine groups than in the
      corresponding control groups (all P < 0.01), significantly higher in the C57
      lidocaine and apoE ischemia groups than in the C57 ischemia group (both P <
      0.01), however, significantly lower in the apoE lidocaine group than in the apoE
      ischemia group (both P < 0.01). (2) The latency period decreased significantly
      along with the test days in all groups except in the apoE ischemia group (P <
      0.05 or 0.01), significantly longer in the ischemia and lidocaine groups than in
      the corresponding control groups (P < 0.05 or 0.01), significantly longer in the
      C57 lidocaine group than in the C57 ischemia group on the 3 rd day of test [73.1
      (22.1-120.1) s vs. 40.2 (28.4-91.1) s], and in the apoE ischemia group than in
      the C57 ischemia group on the 3 rd and 4 th days of test [88.2 (41.0-120.1) s vs.
      40.2 (28.4-91.1) s, and 78.2 (32.9-120.1) s vs. 46.3 (11.6-81.9) s] (P < 0.05 or
      0.01), and, however, significantly shorter in the apoE lidocaine group than in
      the C57 lidocaine group on the 3rd day of test [39.0 (15.5-103.5) s vs. 73.1
      (22.1-120.1) s], and in the apoE lidocaine group than in the apoE ischemia group
      from the 3 rd to the 5 th days of test [39.0 (15.5-103.5) s vs. 88.2 (41.0-120.1)
      s, 24.9 (11.8-68.0) s vs. 78.2 (32.9-120.1) s, and 29.1 (6.6-57.2) s vs. 66.3
      (14.2-97.0) s respectively] (P < 0.05 or 0.01). (3) The percentage of effective
      search strategy increased significantly along with the test day in all groups
      except in the C57 lidocaine and apoE ischemia groups (P < 0.05 or 0.01),
      significantly lower in the ischemia and lidocaine groups than in the
      corresponding control groups (P < 0.05 or 0.01), significantly lower in the C57
      lidocaine group than in the C57 ischemia group on the 4 th and 5 th days of test
      [25 (0-50)% vs. 50 (25-75)% and 37.5 (0-75)% vs. 50 (50-100)%], and in the apoE
      ischemia group than in the C57 ischemia group from the 3 rd to the 5th days of
      test [25 (0-25)% vs. 50 (25-75)%, 25 (0-25)% vs. 50 (25-75)%, and 25 (0-50)% vs.
      50 (50-100)% respectively] (P < 0.05 or 0.01), and, however, significantly higher
      in the apoE lidocaine group than in the C57 lidocaine group [50 (0-75)% vs. 25 (0
      50)% and 50 (25-100)% vs. 37.5 (0-75)%], and in the apoE lidocaine group than in
      apoE ischemia group [50 (0-75)% vs. 25 (0-25)% and 50 (25-100)% vs. 25 (0-50)%]
      on the 4 th and 5 th days of test (all P < 0.05). CONCLUSION: Transient global
      cerebral ischemia causes significant brain damage, which is more severe in the
      apoE mice than in the C57 mice. Lidocaine significantly worsens the ischemic
      brain damage in the C57 mice, and, however, significantly alleviates the ischemic
      cerebral result in the apoE mice.

PMID- 16409862
TI  - [Protective effects of bicyclol on alcohol-induced liver damage in mice].
AB  - OBJECTIVE: To study the protective effect of bicyclol on alcohol-induced liver
      injury in mice. METHODS: Sixty male mice were randomly divided into 6 groups. Ten
      mice were fed with Lieber-Decarli liquid diet without alcohol and used as normal
      controls. Fifty mice were fed with Lieber-Decarli liquid diet containing 5%
      alcohol for four weeks so as to establish a model of alcohol-induced liver
      damage. Ten mice fed with Lieber-Decarli liquid diet containing 5% alcohol for
      four weeks were used as model group. Bicyclol in a dose of either 200 or 300 .kg(
      1).d(-1) was given orally simultaneously with alcohol intake as prevention groups
      (10 mice in each group), and bicyclol in a dose of either 200 or 300 .kg(-1).d(
      1) was given orally 2 weeks after the beginning of alcohol intake as treatment
      groups (10 mice in each group). Twenty-four hours after the last dose of bicyclol
      the mice were decapitated and then their blood samples and livers were taken. The
      serum alanine aminotransferase (ALT), cholesterol (CHOL), and high-density
      lipoprotein/low-density lipoprotein (HDL/LDL), and liver triglyceride (TG), N
      nitrosodimethylamine demethylase (NDMA-DM), glutathione (GSH), glutathione S
      transferase (GST), glutathione reductase (GR), and aldehyde dehydrogenase (ALDH)
      were determined by biochemical assays. The extent of liver damage was evaluated
      by histological examination. RESULTS: Four weeks after alcohol intake the serum
      ALT and TG were 1.9 and 2.7 times those of the normal control group. The levels
      of liver TG of the bicyclol 200 kg(-1).d(-1) and 300 kg(-1).d(-1) treatment
      groups were significantly lower than that of the model group by 28% and 32%
      respectively (both P < 0.05). The levels of liver TG of the bicyclol 200 kg(
      1).d(-1) and 300 kg(-1).d(-1) prevention groups were significantly lower than
      that of the model group by 32%, and 47% respectively (both P < 0.01).
      Pathological changes including steatosis and hepatocyte ballooning degeneration
      were found in the livers of the model group. The levels of liver GSH, GST, and GR
      in the model group decreased by 37%, 22%, and 19% in comparison with the normal
      control group. The levels of liver GSH and GST of the bicyclol prevention groups
      were normal, and the liver GR level was 1.2 times that of the normal control
      group. The liver NDMA-DM activity of the model group was 1.9 times that of the
      normal control group and was normal in the bicyclol prevention and treatment
      groups. The liver cytoplasmic ALDH level was 30% lower in the model group than in
      the normal control group (P < 0.05), and was 2.9 times in the bicyclol groups (P
      < 0.01). The serum cholesterol levels of the bicyclol groups were all
      significantly lower than that of the model group (all P < 0.01). The serum levels
      of HDL of the bicyclol prevention groups and treatment were all significantly
      lower than that in the model group (P < 0.01 or P < 0.05). CONCLUSION: Bicyclol
      protects mice against alcohol-induced hepatotoxicity by reduction of hepatic
      steatosis and cellular damage, acceleration of alcohol and aldehyde elimination
      and anti-peroxidation.

PMID- 16409863
TI  - [Expression of early growth response gene-1 and its correlative genes in
      autogenous vein graft and significance thereof: an experiment with rats].
AB  - OBJECTIVE: To investigate the expression of early growth response gene-1 (Egr-1)
      and its correlative genes: platelet-derived growth factor-B (PDGF-B) gene and
      transforming growth factor-beta(1) (TGF-beta(1)) gene, in autogenous vein graft
      and the relationship of the expression of these genes to intimal hyperplasia
      (IH). METHODS: A segment of the right common jugular vein was transplanted to the
      infra-renal abdominal aorta of the same individual so as to establish an
      autogenous vein graft model in 90 Wistar rats. Vein samples were harvested 1, 2,
      6, and 24 hours, 3 and 7 days, and 2, 4, and 6 weeks after the operation to
      undergo histological examination. In situ hybridization and RT-OCR were performed
      to examine the mRNA expression of Egr-1, PDGF-B, and TGF-beta(1). Western
      blotting and immunohistochemistry were used to detect the protein expression of
      Egr-1, PDGF-B, and TGF-beta(1). The contralateral common jugular vein was used as
      control. RESULTS: Histological examination showed a great amount of vascular
      smooth muscle cells (VSMCs) in the tunica intima and tunica media of the vein
      graft since the 7 th day after the transplantation. mRNA expression of Egr-1,
      PDGF-B, and TGF-beta(1) was not found in the normal veins. The expression of Egr
      1 mRNA in the vein graft showed a biphasic manner: increased remarkably 1 h after
      the transplantation, decreased during the period 6 h approximately 3 d after, re
      increased 7 d after, and peaked 4 weeks after. The mRNA expression of PDGF-B
      appeared 6 h after, and peaked 2 weeks after, and began to decrease since the 4
      th week. The mRNA expression of TGF-beta(1) increased 6 h after, peaked 7d after,
      and began to decrease 2 weeks after. The protein expression of Egr-1 appeared 2 h
      after, and peaked 4 weeks after; the protein expression of PDGF-B appeared 6 h
      after and peaked 4 weeks after; and the protein expression of TGF-beta(1).
      Appeared 24 h after and peaked 2 weeks after. Immunohistochemistry showed that
      Egr-1 protein expression was mainly in the VSMCs and monocytes/macrophages in the
      tunica media in the early stage after transplantation, and peaked 4 weeks later
      with a positive cell rate of 40% +/- 9%; in the early stage after transplantation
      PDGF-B protein expression was mainly in the VSMCs in the tunica media, and peaked
      4 weeks after with a positive cell rate of 45% +/- 4%; the TGF-beta(1) protein
      expression peaked 2 weeks after with a positive cell rate of 41% +/- 7%; and 4
      weeks after transplantation the protein expressions of Egr-1, PDGF-B, and TGF
      beta(1) were all mainly in the VSMCs in the newly-grown tunica intima.
      CONCLUSION: The IH of vein graft is affinitive with the expression of Egr-1, PDGF
      B, and TGF-beta(1). The activation and expression of Egr-1, PDGF-B, and TGF
      beta(1) depend on Egr-1 and may contribute to the high expression of Egr1 via a
      feedback mechanism.

PMID- 16409864
TI  - [Study of the role of insulin and insulin receptor in allergic airway
      inflammation of rats].
AB  - OBJECTIVE: To reveal the possible mechanism underlying the inverse relationship
      between IDDM and asthma and the role of insulin and insulin receptor in allergic
      airway inflammation. METHODS: Diabetes mellitus was induced in rats by
      intraperitoneal injection of streptozotocin. Rats were sensitized by subcutaneous
      injection of ovalbumin (OVA) and challenged with an aerosolized solution of 1%
      OVA for 20 min 14 days after sensitization to provoke allergic airway
      inflammation. Sixty-four male Sprague-Dawley rats were divided into 8 groups:
      group A (asthma), group D (diabetes), group I (insulin treated), group AD (asthma
      + diabetes), group AI (asthma + insulin treated), group DI (diabetes + insulin
      treated), group ADI (asthma + diabetes + insulin treated), and group C (control).
      Blood glucose measurements, total and differential leukocyte counts and serum
      insulin measurements were carried out. Bronchoalveolar lavage (BAL) were
      performed, total and differential cell counts were determined. Hematoxylin-eosin
      stained paraffin section of lung tissue was examined to observe the histological
      changes. Immunohistochemistry method was used to describe the distribution of
      insulin receptor, and the expression of insulin receptor mRNA were measured by RT
      PCR. RESULTS: All groups of diabetes had higher blood glucose levels than non
      diabetes groups. After antigen challenge, the rats of group A, AI, ADI exhibited
      airway inflammation characterized by significantly elevated eosinophils and
      neutrophils, group AD only exhibited mild airway inflammation. The serum insulin
      levels were higher in groups ADI, AI and A (27 mIU/L +/- 8 mIU/L, 83 mIU/L +/- 12
      mIU/L, 71 mIU/L +/- 12 mIU/L respectively) compared with their respective control
      group (group DI, I, C, 15 mIU/L +/- 4 mIU/L, 64 mIU/L +/- 9 mIU/L; 49 mIU/L +/-
      14 mIU/L respectively). Immunohistochemistry staining for insulin receptor
      revealed a diffused distribution pattern of the receptor in the lung tissue.
      Positive cells infiltrating in the alveolar spaces, submucosa of bronchus, blood
      vessels, and bronchial mucosa were increased significantly in groups A, AI and
      ADI. In groups with induced diabetes the expression of insulin receptor mRNA was
      elevated compared with that in the non-diabetes groups (0.2588 +/- 0.0809 vs
      0.0896 +/- 0.0308, P = 0.00). CONCLUSION: Administration of low dose insulin
      aggravated airway inflammation to antigen provocation in rats. Insulin secretion
      is increased in the presence of inflammation. In the lung of antigen-challenged
      rats, insulin receptors on the surface of the infiltrating inflammatory cells and
      bronchial secretory cells are increased.

PMID- 16409865
TI  - [Gene expression profiles and proteomics analysis of the cell transfected with
      the mutant type of COOH-terminal deleted of hepatitis B virus X].
AB  - OBJECTIVE: To investigate the mechanism of the different biological impacts of
      HBx3'-40, an engineered deletion mutant lacking the last 40 C-terminal amino
      acids. METHOD: Human hepatocellular cells of the line Huh7 were transfected with
      HBx3'-40 or wtHBx (wild type HBx) constructs. An oligo cDNA microarray containing
      21074 human genes and Ests was utilized to examine the different gene expression
      between HBx3'-40 and paired control wtHBx cells. A series of methods, including
      immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis (2
      DE), silver staining, and PDQuest 2-D analysis software were used to analyze the
      differential protein-spots between HBx3'-40 and wtHBx cells. Selected
      differential protein-spots were identified with peptide mass fingerprinting based
      on matrix-assisted laser desorption/ionization time-of-fight mass spectrometry
      (MALDI-TOF-MS) and database searching. RESULTS: 165 (0.82%) candidate genes
      showing aberrant expression under HBx3'-40 induction were identified, of which
      144 were up-regulated while 21 were down-regulated. Compared with wtHBx group,
      there were 135 +/- 13 differently protein spots in HBx3'-40 group by 2-DE. Of
      them, 7 significantly different protein spots were identified using mass
      spectrometry and computer matching with protein database. Most of the differently
      expressed genes and proteins were involved in transcription, oncogenes and tumor
      suppressor genes or protein, cell adhesion, signal transduction pathways,
      metabolisms, etc. CONCLUSION: The mutant HBx affects cell genes and proteins
      involved in various processes, especially in regulation of liver metabolism.

PMID- 16409866
TI  - [Regulation of differentiation and proliferation of epiphysis stem cells by
      Notch1 signaling system].
AB  - OBJECTIVE: To investigate the regulation of differentiation and proliferation of
      epiphysis stem cells by Notch1 signaling system. METHODS: Costocostal cartilage
      was taken from a SD rat. Epiphysis stem cells were isolated and cultured.
      Recombinant human nuclear factor-kappaB (rhNF-kappaB), an activator of the Notch
      signaling system, and gamma-secretase inhibitor (MW167), an inhibitor of the
      Notch signaling system, were added into the culture medium respectively. The
      cells cultured in the medium added with phosphate-buffered saline were used as
      control group. Then the cultured cells were collected. The expression of the
      homologous Notch receptors and homologous Notch ligands was detected by RT-PCR.
      Immunohistochemistry was used to detect the levels of collagen II, collagen X,
      and proliferating cell nuclear antigen (PCNA). MTT method was used to calculate
      the growth curve. The cell phase was examined by flow cytometry. The level of
      alkaline phosphatase (AP) was measured. Western blotting was used to detect the
      protein expression of collagen II, collagen X, and stathmin, a signaling protein
      of proliferation. RESULTS: Only 2 the expression of the receptor Notch1 and the
      ligand Jagged1 was found. The expression of PCNA was stronger in the rhNF-kappaB
      group than in the other 2 groups. rhNF-kappaB remarkably promoted the expression
      of collagen II and inhibited the expression of collagen X and MW167 remarkably
      promoted the expression of collagen X and did not remarkably influence the
      expression of collagen II. MTT method showed that rhNF-kappaB significantly
      promote the proliferation of the cells (P = 0.027), and MW167 did not
      significantly promote the cell proliferation (P > 0.05). The percentage of cells
      at S phase of the rhNF-kappaB group was 26.54%, significantly higher than those
      of the MW167 group and control group (8.22% and 6.15%). AP was significantly
      expressed in the MW167 group, and less expressed in the other groups. Western
      blotting showed a significantly increased expression of collagen X protein and
      decreased expression of collagen II protein and stathmin. CONCLUSION: When the
      Notch signaling system is activated the epiphysis stem cells proliferate, and
      when the Notch signaling system is suppressed the epiphysis stem cells
      differentiate.

PMID- 16409867
TI  - [Adenovirus-mediated CTLA4Ig and OX40Ig gene transfer induces long-term survival
      of cardiac allografts in rats].
AB  - OBJECTIVE: To investigate the potential role of CTLA4Ig gene and OX40Ig protein
      in inducing transplantation tolerance and the mechanisms thereof. METHODS: Thirty
      Lewis rats underwent transplantation of the hearts of DA rats and then randomly
      divided into five equal groups: control group, blank virus AdEGFP treated group
      (adenovirus containing EGFP at the dose of 1-5 x 10(9) pfu/ml was infused via
      portal vein immediately after the operation), AdCTLA4Ig treated group, AdOX40Ig
      treated group, and AdCTLA4Ig-IRES-OX40Ig treated group. The cardiac allograft
      survival was monitored by daily palpation. The total cessation of beating was
      defined as rejection and was confirmed by histology. Peripheral venous blood
      samples were collected 0, 3, 7, 10, 14, 21 and 28 days after the administration
      of adenovirus. ELISA was used to detect the expression of CTLA4Ig and OX40Ig.
      Twenty days after the heart transplantation single splenocyte suspension was
      prepared from surviving Lewis rats to be used as responder. The spleens of the
      normal donor-DA rats and the third strain DA rats to prepare single cell
      suspension of the same density to perform mixed lymphocyte reaction (MLR). Then
      recombinant IL-2 was added into the mixed MLR system to observe t?if the MLR
      could be reversed. Twenty days after the heart transplantation the splenocytes of
      the tolerating Lewis rats were injected into the lingual vein of the normal Lewis
      rats to observe the delayed type hypersensitivity (DTH) of the transferred Lewis
      rat to normal rat splenocytes. RT-PCR was used to detect the mRNA expression of
      IL-2, interferon-gamma, IL-4, and IL-10. RESULTS: The survival time of the
      AdCTLA4Ig-IRES-OX40Ig treated group was 151.5 d +/- 42.6 d, significantly longer
      than those of the AdOX40Ig treated group (60.2 d +/- 11.4 d (P = 0.003),
      AdCTLA4Ig (43.2 d +/- 11.1 d, P = 0.0026), control group (5.7 d +/- 0.5 d, P =
      0.000 43), and AdEGFP treated group (5.2 d +/- 0.4 d, P = 0.000 43). CTLA4Ig
      and/or OX40Ig proteins were expressed at a high level in the adenoviral treated
      rats. Compared with the control group the splenocytes of the AdCTLA4Ig-IRES
      OX40Ig, AdCTLA4Ig, and AdOX40Ig treated groups displayed donor-specific
      hyporesponsiveness (P = 0.0016, 0.0026 and 0.001), which could be partly reversed
      by the addition of exogenous IL-2. Moreover, the hyporesponsiveness could be
      transferred to the same strain rats through adoptive transfer. In comparison with
      the normal controls, the expression of Th1 type cytokines, such as IL-2 and IFN
      gamma, was significantly decreased in the tolerating rats and significantly
      increased in the rats with rejection; however the expression of the Th2 type
      cytokines, such as IL03 and IL-10, was significantly increased in the tolerating
      rats and significantly decreased in the rats with rejection, showing a deviation
      of Th1/Th2 type cytokines. CONCLUSION: AdCTLA4Ig-IRES-OX40Ig-mediated genes
      transfer renders prolonged expression of CTLA4Ig and OX40Ig in Lewis recipient
      rats, leading to a long-term survival of cardiac allografts. The induced
      tolerance is donor-specific, and the mechanisms may be associated with T cell
      anergy, deviation of Th1/Th2, and the regulatory T cells.

PMID- 16409880
TI  - FOOD: a multicentre randomised trial evaluating feeding policies in patients
      admitted to hospital with a recent stroke.
AB  - OBJECTIVES: To determine whether routine oral nutritional supplementation of a
      normal hospital diet improves outcome after stroke (Trial 1); whether early tube
      feeding improves the outcomes of dysphagic stroke patients (Trial 2); and if tube
      feeding via a percutaneous endoscopic gastrostomy (PEG) results in better
      outcomes than that via a nasogastric tube (NG) (Trial 3). DESIGN: The Feed Or
      Ordinary Diet (FOOD) trial was a family of three pragmatic, randomised controlled
      trials (RCTs). They shared facilities for randomisation, data collection, follow
      up and coordination. Patients could be co-enrolled in more than one of these
      trials. SETTING: Patients were enrolled in 131 hospitals in 18 countries.
      PARTICIPANTS: A total of 5033 patients who had been admitted to hospital with a
      recent stroke were enrolled in the trials between November 1996 and July 2003.
      INTERVENTIONS: In Trial 1, patients who could swallow within the first 30 days of
      admission were allocated to normal hospital diet versus normal hospital diet plus
      oral nutritional supplements (equivalent to 360 ml of 1.5 kcal/ml, 20 g of
      protein per day) until hospital discharge. In Trial 2, dysphagic patients
      enrolled within 7 days of admission were allocated to early enteral tube feeding
      versus avoid any enteral tube feeding for at least 1 week. In Trial 3, dysphagic
      patients were allocated within 30 days of admission to receive enteral tube
      feeding via PEG versus NG. MAIN OUTCOME MEASURES: Survival and the modified
      Rankin scale (MRS), a measure of functional outcome (grade 0 indicating no
      symptoms and grade 5 indicating severe disability, requiring help day and night).
      The primary outcomes were measured 6 months after enrollment, blind to treatment
      allocation, by the patient or their proxy completing a postal or telephone
      questionnaire. RESULTS: In Trial 1, 4023 patients were enrolled by 125 hospitals
      in 15 countries. Only 314 (7.8%) patients were judged undernourished at baseline.
      Vital status and MRS at the end of the trial were known for 4012 (99.7%) and 4004
      (99.5%), respectively. Of the 2007 allocated normal hospital diet, 253 (12.6%)
      died, 918 (45.7%) were alive with poor outcome (MRS 3-5) and 823 (41.1%) had a
      good outcome (MRS 0-2). Of the 2016 allocated oral supplements, 241 (12.0%) died,
      953 (47.3%) were alive with poor outcome and 813 (40.4%) had a good outcome. The
      supplemented diet was associated with an absolute reduction in risk of death of
      0.7% (95% CI -1.4 to 2.7; p = 0.5) and a 0.7% (95% CI -2.3 to 3.8, p = 0.6)
      increased risk of death or poor outcome. In Trial 2, a total of 859 patients were
      enrolled by 83 hospitals in 15 countries. MRS at the end of the trial was known
      for 858 (99.9%). At follow-up, of 429 allocated early tube feeding, 182 (42.4%)
      died, 157 (36.6%) were alive with poor outcome (MRS 4-5) and 90 (21.0%) had a
      good outcome (MRS 0-3). Of 430 allocated avoid tube feeding 207 (48.1%) died, 137
      (31.9%) were alive with poor outcome and 85 (19.8%) had a good outcome. Early
      tube feeding was associated with an absolute reduction in risk of death of 5.8%
      (95% CI -0.8 to 12.5; p = 0.09) and a reduction in death or poor outcome of 1.2%
      (95% CI -4.2 to 6.6; p = 0.7). In Trial 3, 321 patients were enrolled by 47
      hospitals in 11 countries. Of 162 allocated PEG, 79 (48.8%) died, 65 (40.1%) were
      alive with poor outcome and 18 (11.1%) had good outcome. Of 159 allocated NG, 76
      (47.8%) died, 53 (33.3%) were alive with poor outcome and 30 (18.9%) had good
      outcome. PEG was associated with an increase in absolute risk of death of 1.0%
      (95% CI -10.0 to 11.9; p = 0.9) and an increased risk of death or poor outcome of
      7.8% (95% CI 0.0 to 15.5; p = 0.05). CONCLUSIONS: The results of Trial 1 would be
      compatible with oral supplementation being associated with a 1-2% absolute
      benefit or harm, but do not support routine supplementation of hospital diet for
      unselected stroke patients who are predominantly well nourished on admission. In
      Trial 2, the data suggest that a policy of early tube feeding may substantially
      reduce the risk of dying after stroke and it is very unlikely that the
      alternative policy of avoiding early tube feeding would significantly improve
      survival. Improved survival may be at the expense of increasing the proportion
      surviving with poor outcome. These data might usefully inform the difficult
      discussions about whether or not to feed a patient with a severe stroke. In Trial
      3, the data suggest that in the first 2-3 weeks after acute stroke, better
      functional outcomes result from feeding via NG tube than PEG tube, although there
      was no major difference in survival. These data do not support a policy of early
      initiation of PEG feeding in dysphagic stroke patients. Future research might be
      focused on making NG tube feeding safer and more effective, also studies need to
      confirm the increased risk of gastrointestinal haemorrhage associated with tube
      feeding and, if confirmed, establish whether any interventions might reduce this
      risk. Future work might also aim to establish why worse functional outcomes
      occurred in PEG-fed patients because patients with prolonged dysphagia or
      intolerance of an NG tube are inevitably fed via a PEG tube.

PMID- 16409879
TI  - The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and
      memantine for Alzheimer's disease.
AB  - OBJECTIVES: To provide an update review of the best quality evidence for the
      clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and
      galantamine for mild to moderately severe Alzheimer's disease (AD) and of
      memantine for moderately severe to severe AD. DATA SOURCES: Electronic databases,
      experts in the field and manufacturer submissions to the National Institute for
      Health and Clinical Excellence (NICE). REVIEW METHODS: A systematic review of the
      literature and an economic evaluation were undertaken. The quality of included
      randomised controlled trials (RCTs) was assessed using criteria developed by the
      NHS Centre for Reviews and Dissemination. An outline assessment of economic
      evaluations was undertaken using a standard checklist. The clinical and cost
      effectiveness data were synthesised through a narrative review with full
      tabulation of the results of included studies. Where appropriate, meta-analysis
      of data was undertaken. RESULTS: For mild to moderately severe AD, the results of
      the study suggested that all three treatments were beneficial when assessed using
      cognitive outcome measures. Global outcome measures were positive for donepezil
      and rivastigmine, but mixed for galantamine. Results for measures of function
      were mixed for donepezil and rivastigmine, but positive for galantamine.
      Behaviour and mood measures were mixed for donepezil and galantamine, but showed
      no benefit for rivastigmine. For memantine, two published RCTs were included; in
      one of these trials the participants were already being treated with donepezil.
      The results suggest that memantine is beneficial when assessed using functional
      and global measurements. The effect of memantine on cognitive and behaviour and
      mood outcomes is, however, less clear. Literature on the cost-effectiveness of
      donepezil, rivastigmine and galantamine was dominated by industry-sponsored
      studies, and studies varied in methods and results. Of the three UK studies, two
      report donepezil as not cost-effective, whereas a third study reports an
      additional cost (1996 pounds sterling) of between 1200 pounds sterling and 7000
      pounds sterling per year in a non-severe AD health state (concerns over these
      estimates are raised, suggesting that they may underestimate the true cost
      effectiveness of donepezil). Cost-effectiveness analysis undertaken in this
      review suggests that donepezil treatment has a cost per quality-adjusted life
      year (QALY) in excess of 80,000 pounds sterling, with donepezil treatment
      reducing the mean time spent in full-time care (delays progression of AD) by 1.42
      1.59 months (over a 5-year period). From four published cost-effectiveness
      studies, two UK studies report additional costs associated with rivastigmine
      treatment. Cost-effectiveness analysis undertaken in the current review suggests
      that rivastigmine treatment has a cost per QALY in excess of 57,000 pounds
      sterling, with rivastigmine treatment reducing the mean time spent in full-time
      care (delays progression) by 1.43-1.63 months (over a 5-year period). From five
      published cost-effectiveness studies, one UK study reports a cost per QALY of
      8693 pounds sterling for 16-mg galantamine treatment and 10,051 pounds sterling
      for 24-mg galantamine treatment (concerns raised suggest that this may
      underestimate the true cost-effectiveness of galantamine). Cost-effectiveness
      analysis undertaken in the present review suggests that galantamine treatment has
      a cost per QALY in excess of 68,000 pounds sterling, with galantamine reducing
      the time spent in full-time care (delays progression) by 1.42-1.73 months (over a
      5-year period). From two published cost-effectiveness studies, one reports
      analysis for the UK, finding that memantine treatment results in cost savings and
      benefits in terms of delaying disease progression (concerns raised suggest that
      this may underestimate the true cost-effectiveness of memantine). In the current
      review, the cost-effectiveness of memantine has not been modelled separately, but
      where alternative parameter inputs on the cost structure and utility values have
      been used in a reanalysis using the industry model, the cost-effectiveness is
      reported at between 37,000 pounds sterling and 52,000 pounds sterling per QALY,
      with this alternative analysis still based on what is regarded as an optimistic
      or favourable effectiveness profile for memantine. CONCLUSIONS: Although results
      from the clinical effectiveness review suggest that these treatments may be
      beneficial, a number of issues need to be considered when assessing the results
      of the present review, such as the characteristics of the participants included
      in the individual trials, the outcome measures used, the length of study
      duration, the effects of attrition and the relationship between statistical
      significance and clinical significance. Many included trials were sponsored by
      industry. For donepezil, rivastigmine and galantamine, the cost savings
      associated with reducing the mean time spent in full-time care do not offset the
      cost of treatment sufficiently to bring estimated cost-effectiveness to levels
      generally considered acceptable by NHS policy makers. It is difficult to draw
      conclusions on the cost-effectiveness of memantine; it is suggested that further
      amendments to the potentially optimistic industry model (measure of effect) would
      offer higher cost per QALY estimates. Future research should include: information
      on the quality of the outcome measures used; development of quality of life
      instruments for patients and carers; studies assessing the effects of these
      interventions of durations longer than 12 months; comparisons of benefits between
      interventions; and research on the prediction of disease progression.

PMID- 16409881
TI  - The clinical effectiveness and cost-effectiveness of computed tomography
      screening for lung cancer: systematic reviews.
AB  - OBJECTIVES: The aim of this review is to examine the clinical and cost
      effectiveness of screening for lung cancer using computed tomography (CT) to
      assist policy making and to clarify research needs. DATA SOURCES: Electronic
      databases and Internet resources. REVIEW METHODS: A systematic review was
      undertaken and selected studies were assessed using the checklists and methods
      described in NHS Centre for Reviews and Dissemination (CRD) Report 4. Separate
      narrative summaries were performed for clinical effectiveness and cost
      effectiveness. Cost-effectiveness analysis resulting in a cost per quality
      adjusted life-year was not feasible, therefore the main elements of such an
      appraisal were summarised and the key issues relating to the existing evidence
      base were discussed. RESULTS: Twelve studies of CT screening for lung cancer were
      identified, including two randomised controlled trials (RCTs) and ten studies of
      screening without comparator groups. The quality of reporting of these studies
      was variable, but the overall quality was adequate. The two RCTs were of short
      duration (1 year) and therefore there was currently no evidence that screening
      improves survival or reduces mortality. The proportion of people with abnormal CT
      findings varied widely between studies (5-51%). The prevalence of lung cancer
      detected was between 0.4% and 3.2% (number need to screen to detect one lung
      cancer = 31-249). Incidence rates of lung cancer were lower (0.1-1% per year).
      Detection of stage I and resectable tumours was high, 100% in some studies.
      Adverse events, as a result of investigation or surgery, or the screening process
      per se were poorly reported. Incidental findings of other abnormalities requiring
      medical follow-up were reported to be as high as 49%. Six full economic
      evaluations of population CT screening programmes for lung cancer were included
      in the review. The magnitude of cost-effectiveness ratios reported varied widely.
      None was set in the UK and generalisation was complicated by wide variation in
      the data used in different countries and a paucity of UK data for comparison. All
      six made the fundamental assumption that screening with CT for lung cancer
      reduced mortality. At the current time, there is no evidence to support that
      assumption. In the absence of evidence of health gains from screening for lung
      cancer, in terms of either quantity or quality of life, and faced with a range of
      uncertainties, from the frequency of abnormal screening findings within a
      population to the natural history of screening detected lung cancers, it is not
      feasible at the current time to develop accurately and meaningfully an economic
      argument for CT screening for lung cancer in the UK. For subgroups, in particular
      certain occupational groups, there is evidence of increased risk of lung cancer,
      but the role of screening has not been demonstrated by the current studies.
      CONCLUSIONS: The accepted National Screening Committee criteria are not currently
      met, with no RCTs, no evidence to support clinical effectiveness and no evidence
      of cost-effectiveness. RCTs are needed to examine the effect of CT screening on
      mortality, either with whole-population screening or for particular subgroups; to
      determine the rate of positive screening and detected lung cancers. Research is
      also needed to understand better the natural history and epidemiology of
      screening-detected lung cancers, particularly small, well-differentiated
      adenocarcinomas; as well as the impacts on quality of life. Increased collection
      is needed of UK health service data regarding resource use and safety data for
      lung cancer management and services. Research is also needed into the feasibility
      and logistics of tracing people who have in the past worked in industry where
      there was exposure to lung carcinogens.

PMID- 16409885
TI  - Is the crisis in clinical research being effectively addressed?

PMID- 16409886
TI  - Outcomes of National Institutes of Health peer review of clinical grant
      applications.
AB  - PURPOSE: We previously reported that National Institutes of Health (NIH) peer
      review outcomes in 2002 were slightly but significantly less favorable for grant
      applications for clinical research than for laboratory research. The present
      analysis was undertaken to determine if factors related to the review process
      might contribute to this difference. METHODS: The impact of each of the following
      factors on median priority scores and funding rates for clinical and nonclinical
      R01 grant applications was evaluated: (1) the percentage of clinical applications
      assigned for review to a study section, (2) the requested direct costs, and (3)
      the clinical research experience of the reviewers. RESULTS: Confirming our
      previous observation, in both 1994 and 2004, median priority scores and funding
      rates for R01 applications were less favorable for clinical research. In 1994,
      clinical applications did not fare as well in study sections reviewing relatively
      low percentages of clinical applications. This was not the case in 2004. Although
      requested direct costs were greater for clinical than for nonclinical R01
      applications, median priority scores within each category were actually more
      favorable for applications requesting greater funding. Assignment of priority
      scores was not different for reviewers with or without experience conducting
      clinical research. CONCLUSION: These data do not support the hypothesis that the
      less favorable review outcomes for clinical applications are related to these
      review factors. We suggest that peer review outcomes for clinical research will
      benefit from the recent refinement of NIH review criteria, emphasizing the unique
      contributions of clinical investigation, and from increased training
      opportunities for clinical investigators.

PMID- 16409889
TI  - Current science of regenerative medicine with stem cells.
AB  - Regenerative medicine with stem cells holds great hope for the treatment of
      degenerative disease. The medical potential of embryonic stem cells remains
      relatively untapped at this point, and significant scientific hurdles remain to
      be overcome before these cells might be considered safe and effective for uses in
      patients. Meanwhile, adult stem cells have begun to show significant capabilities
      of their own in repair of damaged tissues, in both animal models and early
      patient trials.

PMID- 16409887
TI  - Insulin therapy, glycemic control, and cardiovascular risk factors in young Latin
      Americans with type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes has been linked to an increased risk of
      cardiovascular (CV) disease, but this risk has not been well documented in young
      patients, especially of Latin American descent. Also, the potential CV benefits
      of insulin therapy have not been evaluated in young patients with type 2
      diabetes. The objectives of this study were to determine any gender-related
      difference in the presence of CV risk factors in young Latin Americans with
      poorly controlled type 2 diabetes and the effect of intensive insulin therapy on
      these CV risk factors. METHODS AND RESULTS: Fifty-seven Latin American patients
      with type 2 diabetes between the ages 18 and 45 years were evaluated at baseline.
      All women were premenopausal and had regular menstrual periods. The mean body
      mass index (BMI) was > 30 kg/m2 in both genders. Percent body fat, percent
      hemoglobin A1c, and lipoprotein profiles were similar between genders. Highly
      sensitive C-reactive protein (CRP) levels were elevated and similar between
      genders (p = .4). Leukocyte adhesion molecules (intercellular adhesion molecule
      1, vascular adhesion molecule 1, E-selectin) and monocyte chemoattractant protein
      1 were elevated, whereas adiponectin levels were below normal in both gender
      groups. Urinary albumin excretion was similar between genders and did not show
      any relationship with any of the variables. In women, there was a direct
      relationship between waist circumference and high-sensitivity CRP levels (rho =
      .53, p = .01). No other significant relationships were observed. Eighteen Latin
      American patients with type 2 diabetes completed up to 104 weeks of post
      intervention with insulin monotherapy. In these patients, glycemic, lipoprotein,
      and anthropometric measurements were obtained every 12 weeks. Highly sensitive
      CRP, leukocyte adhesion molecules, and urinary albumin excretion, among other
      tests, were obtained every 52 weeks. At 52 and 104 weeks, body weight, BMI, waist
      circumference, and percent body fat increased in a parallel and significant
      manner. Despite a significant decrease in percent hemoglobin A1c (22.2%; p = <
      .0001), lipid and lipoprotein profiles, highly sensitive CRP, leukocyte adhesion
      molecules, and other nontraditional CV risk factors did not change significantly.
      CONCLUSIONS: In young, obese, Latino type 2 diabetic patients, improvement in
      glycemic control with insulin monotherapy was not associated with a parallel
      improvement in markers of vascular inflammation. Premenopausal Latino women with
      uncontrolled type 2 diabetes have CV risks comparable to Latino diabetic men of
      the same age. Obesity and underlying insulin resistance may counteract the
      potential CV benefits associated with insulin therapy in lean diabetic patients.
      Weight loss could be a potential therapeutic modality to improve CV risk in
      Latino type 2 diabetic patients, especially women.

PMID- 16409890
TI  - Research ethics, science policy, and four contexts for the stem cell debate.
AB  - There are plainly conscientious differences of opinion among scientists,
      politicians, and the public in respect of both the ethics of embryonic stem cell
      research and the more general question of the role of public policy in setting
      parameters for what is legal and what is funded in the biosciences. Although
      professional discussion of embryonic stem cell research is not hampered by the
      often misleading oversimplifications of the press, it remains true that the wide
      range of ethical options is rarely explored. These varied positions arise from a
      series of at least six logically distinct policy options, which we may summarize
      in these terms: (a) All use of human embryos for research is wrong. (b) Excess in
      vitro embryos may be used, but others should not be created for the purpose. (c)
      In vitro embryos, but not clonal embryos, may be created with the intent of using
      them for research. (d) Clonal embryos, but not in vitro embryos, may be created
      with the intent of using them for research. (e) Only certain excess embryos
      destroyed before a certain date should be used. (f) Only certain excess embryos
      created before a certain date should be used. Moreover, in any policy permitting
      research use of the embryo, two further sets of issues are raised. First is the
      question of consent. Second is the question of time limits. As advancements in
      biotechnology shape the possibilities of the twenty-first century and hold out
      both promise and threat to the human future, it is crucial that we develop a
      national and global conversation that both encourages science and its potential
      and takes wider social responsibility for the purposes for which science is
      engaged.

PMID- 16409897
TI  - The effect of clinical UVA/B exposures on urinary urocanic acid isomer levels in
      individuals with caucasian type (II/III) skin types.
AB  - Terrestrial ultraviolet radiation (UVR) exposure, consisting of ultraviolet A
      (320-40 nm) and B (290-320 nm), results in the photoisomerizion of epidermal
      trans-urocanic acid (trans-UCA) to cis-urocanic acid (cis-UCA), a potential
      suppressor of local and systemic immune responses. This study examines urinary
      UCA isomers as biomarkers of UVA/B exposure. It presents results measuring both
      cis- and trans-UCA in human urine samples collected from a group of study
      subjects (skin types II/III) that underwent controlled UVA/B exposures similar to
      those administered in commercial suntanning parlors. The UCA isomers were
      purified from urine using C18 solid-phase extraction columns followed by high
      performance liquid chromatography (HPLC) with UV absorbance (268 nm) detection.
      The UCA biomarker was expressed as the ratio of cis-UCA to trans-UCA (UCA ratio),
      or as cis-UCA concentration corrected for urine volume using creatinine (cis-UCA
      Cr). The UCA ratio increased over baseline in the urine of individuals exposed to
      UVA/B. A single exposure to approximately 70 percent minimal erythema dose (MED)
      of UVR (95 % UVA/5 % UVB to approximately 90 % of skin area) produced a 4.75-fold
      increase in the UCA ratio (p< 0.001) relative to baseline. Repeated daily UV
      exposures of similar doses produced a minimal increase in UCA ratio above that of
      the single UV exposure. These findings indicate that UCA cis-trans ratio holds
      promise as a biomarker for recent solar UV exposure.

PMID- 16409898
TI  - Androgenetic alopecia and coronary artery disease in women.
AB  - The meaningful association of androgenetic alopecia (AGA) and coronary artery
      disease (CAD) in men has been documented, but few studies, if any, have focused
      on this association in women. This study was carried out on 106 women under the
      age 55, who completed angiography procedures for diagnosis of coronary artery
      disease. The aim of study was to assess the relationship between androgenetic
      alopecia and coronary heart disease in women. The clinical and paraclinical
      information was obtained by personal interview, physical examination, and review
      of patients' files. Androgenetic alopecia in the patients was assessed blindly by
      a dermatologist, using Ludwig's baldness grading system (I to III). According to
      the angiographic studies, 51 cases had CAD and 55 subjects did not. On the other
      hand, 21 patients had female AGA (Grade I, 15; Grade II, 3; Grade III, 3 cases).
      The correlation of AGA and CAD, AGA and previous history of myocardial
      infarction, and graying of hair and CAD were statistically significant (p <
      0.05), after adjustment of data for differences in age. These data support the
      hypothesis that female AGA, like male pattern baldness, is associated with CAD in
      women under the age 55.

PMID- 16409899
TI  - Colchicine and benzathine penicillin in the treatment of Behcet disease: a case
      comparative study.
AB  - Behcet disease is a chronic relapsing disease characterized by multiple signs and
      symptoms such as recurrent orogenital ulceration, eye involvement, skin
      manifestations, and other systemic involvement. Multiple therapeutic modalities
      have been used to treat Behcet disease. These agents act through different
      mechanisms and are associated with a variety of side effects. We performed a case
      comparative study to evaluate efficacy of combined colchicine and benzathine
      penicillin in the treatment and prophylaxis of Behcet disease. Sixty-six patients
      who fulfilled the international study group criteria for diagnosis of Behcet
      disease were included. The patients were divided into three groups: group 1 (20
      patients) received 1.2 Mu benzathine penicillin injection monthly; group 2 (21
      patients) received two tablets of colchicine daily (each tablet contained 0.5
      mg); and group 3 (25 patients) received both 1.2 Mu benzathine penicillin
      injection monthly and two tablets of colchicine daily. Each patient was followed
      up monthly for 5 months, 4 months on treatment and 1 additional month followup.
      The clinical manifestation index (CMI), the numerical sum of the clinical
      features, was calculated for each patient initially and then monthly. Pathergy
      test was performed for each patient monthly. The CMI was reduced by colchicine
      and benzathine penicillin treatment, and the reduction was highly significant.
      The reduction in the CMI remains satisfactory and good for 1 month after stopping
      the treatment. When each colchicine and benzathine Penicillin are used alone the
      index is also reduced significantly, but this reduction is much less than when
      both drugs are used together and there is also rapid and earlier relapse. Based
      on our findings, the combination of colchicine and benzathine penicillin appears
      to be of greater efficacy in the treatment of Behcet disease than the use of
      either drug alone.

PMID- 16409900
TI  - Cyclophosphamide pulses with oral prednisolone in the treatment of pemphigus: a
      pilot study.
AB  - An open labeled clinical trial aimed at assessing the efficacy and safety of
      pulse intravenous cyclophosphamide with daily oral prednisolone in the treatment
      of pemphigus was carried out. Twenty-six patients (12 men, 14 women; mean age,
      48.4 years), comprising 25 cases with pemphigus vulgaris and 1 with pemphigus
      vegetans (< 10% body surface area involvement) who did not achieve adequate
      control on corticosteroids with or without other adjuvants were included. After
      baseline evaluation, monthly intravenous boluses of cyclophosphamide (15 mg/kg)
      along with daily oral prednisolone (starting dose 1 mg/kg/day, tapered according
      to clinical response) were administered. Patients were assessed monthly for
      clinical activity and side-effects. All patients experienced significant clinical
      improvement within 1 month of starting treatment. Healing of skin and mucosal
      lesions occurred respectively at mean durations of 2.1 and 3.6 months. Three
      weeks to 8 months later, 9 patients had recurrences of activity on
      tapering/withdrawal of prednisolone, mainly in the oral mucosa. Side effects of
      treatment included amenorrhea (3 patients), microscopic hematuria (3) which
      cleared with co-administration of mesna, vomiting (1), weight gain (10),
      gastritis (1), and cataract (2). It is concluded that treatment with monthly
      intravenous cyclophosphamide boluses along with daily oral prednisolone clears
      lesions of pemphigus with < 10 percent body surface involvement, and this may be
      an alternative regimen for pemphigus. Monitoring for adverse effects is
      essential.

PMID- 16409901
TI  - Topical calcipotriol therapy in nail psoriasis: a study of 24 cases.
AB  - There are few reports regarding the treatment of nail psoriasis with topical
      calcipotriol. We undertook a case series study to evaluate the efficacy and
      safety of calcipotriol ointment (50 microg/g) in the treatment of nail psoriasis
      in 24 patients. This study involved 19 women and 5 men with nail psoriasis
      referred to Dermatology clinics of Razi hospital. The duration of trial was from
      October 2002 to September 2004. Informed consent was obtained from all patients
      before entering into the study. The patients applied calcipotriol ointment to the
      affected nails twice daily without occlusion for 3 months. Patients were seen by
      two academic dermatologists initially, after 2 weeks, and then at monthly
      intervals. The efficacy and safety were clinically assessed and any side effect
      was recorded. Patients who showed 50 percent or greater reduction in the baseline
      subungual thickness in at least one nail were considered to be responders and
      were offered continuation of therapy for an additional 2 months. After
      discontinuation of therapy, followup visits were performed at 1 and 2 months.
      After 3 months of therapy, fourteen patients showed significant clinical
      improvement, two of them were completely free from nail lesions after 5 months.
      Calcipotriol was particularly effective in subungual hyperkeratosis, onycholysis,
      and discoloration. In four patients fingertip tenderness and in one case the pain
      of involved distal phalanx were significantly reduced. No clinical response was
      observed in four patients. Only two cases showed adverse reactions. Topical
      Calcipotriol is an effective treatment for nail psoriasis and can be considered
      to be a safe topical treatment in chronic cases; its high tolerability allows
      prolonged usage without severe side effects.

PMID- 16409903
TI  - A review of the effect of occlusive dressings on lamellar bodies in the stratum
      corneum and relevance to transdermal absorption.
AB  - Transdermal drug delivery is becoming a widely used tool in the pharmaceutical
      industry. Many factors can influence the transdermal flux of medication from a
      transdermal drug delivery system. The recently described skin physiology of
      lamellar bodies and skin responses to occlusive dressings provide new insights
      into transdermal drug delivery. This paper reviews the literature on occlusive
      dressings and lamellar bodies as it relates to transdermal drug delivery. An
      understanding of the physiology of lamellar bodies is important to understand and
      improve transdermal drug delivery.

PMID- 16409902
TI  - Efficacy of treatments for mycosis fungoides and Sezary syndrome: nationwide
      survey responses.
AB  - BACKGROUND: Numerous treatments have been used to treat the mycosis fungoides
      (MF) and Sezary syndrome (SS) variants of cutaneous T-cell lymphoma (CTCL). The
      relative efficacy of different treatments is largely unknown. OBJECTIVE: To
      determine the frequency of therapies ranked most effective and least effective
      for treatment of MF and SS in a sampling of dermatologists in the United States.
      METHODS: Fellow members in the American Academy of Dermatology in the United
      States between the ages of 35 and 65 years were surveyed regarding demographic
      variables and treatment efficacy for patch/plaque MF (stages Ia-Ib CTCL), tumor
      stage MF (stage IIb), and erythrodermic MF/SS (stage III). RESULTS: Based on
      1,399 responses, PUVA was preferred for the management of patch/plaque MF. Total
      skin electron beam (TSEB) therapy was preferred for tumor stage MF. Photopheresis
      (extracorporeal photochemotherapy) was preferred for erythrodermic MF/SS,
      followed closely by TSEB. Especially for tumor stage and erythrodermic MF/SS,
      physicians without a clear preference comprised the largest group. No significant
      variation depending on practice type, degree of practitioner experience, or
      geographic location was identified. CONCLUSION: PUVA was the preferred treatment
      for Stage Ia and Ib MF. The predominance of surveys with indeterminate responses
      suggests limited experience and in the treatment of CTCL, especially in advanced
      stages.

PMID- 16409904
TI  - Infections in the elderly.
AB  - As people age they experience more illness and this applies in particular to skin
      infections. Pathogenic states that provide the milieu for infection are more
      common in the elderly. Infections that occur more common in the elderly include
      Gram-positive bacterial infections of the skin, intertriginous infections, herpes
      zoster/shingles and onychomycosis. These will be reviewed in the article. Newer
      treatments such as valacyclovir, famcyclovir, terbinafine and linezolid exist to
      treat these infections. Recognizing the varying presentations enhances the health
      and treatment of disease of elderly patients.

PMID- 16409905
TI  - Stabilize the joint associated with myxoid cyst prior to surgical procedure.

PMID- 16409906
TI  - Versatile sterile field for nail surgery using a sterile glove.
AB  - Nail surgery is frequently done by dermatologists. Post-operative complications
      of nail surgery include infection, bleeding, pain, pyogenic granuloma, and nail
      dystrophy. Infectious complications after nail surgery can be prevented with
      proper aseptic techniques. Standard fenestrated surgical drapes used for a
      sterile field during nail surgery are cumbersome and difficult to keep in place
      during surgery. We present a versatile sterile field for nail surgery using a
      sterile glove that will facilitate nail surgery and concomitantly decrease the
      risk of infection.

PMID- 16409907
TI  - Successful use of infliximab following a failed course of etanercept in a
      pediatric patient.

PMID- 16409908
TI  - Erysipelas after breast cancer treatment (26 cases).
AB  - Erysipelas is a bacterial hypodermal cellulitis usually associated with
      Streptococcal infection. Erysipelas of the upper limbs in women treated for
      breast cancer is relatively rare. We undertook a 10-year retrospective study
      identifying 26 cases of erysipelas of the upper limb following treatment for
      breast cancer; we describe the clinical, therapeutic, and evolutionary aspects.
      The age of our patients ranged from 37 to 80 years with a mean age of 53. All
      patients had a breast surgery and lymphadenectomy. Fifteen patients had
      chemotherapy and 23 had radiotherapy. The erysipelas appeared with an average of
      5.23 years after cancer treatment (3 months to 15 years) and was recurrent in
      nine cases. Lymphedema occurred in eighteen patients. The first signs were fever
      and shivering in 25 patients. The clinical aspect was an inflammatory plaque. The
      physical findings of erysipelas included a raised edge (6 cases), blisters (1
      case), purpura (1 case), and cellulitis (1 case). The portal of entry was not
      found in eleven patients. The upper limb was affected in all cases. Involvement
      of the axillary folds or the chest was observed in eight cases. Treatment with
      penicillin was undertaken for all patients; the length of treatment varied from
      11 to 26 days. Lympadenectomy and radiotherapy in breast cancer may lead to
      lymphedema, which can be evident or sometimes discrete. Those patients who
      developed erysipelas in our series usually fared well with treatment, but many
      had recurrences attributed to persistent lymphedema. It was also of note that for
      many patients in this series, the portal of entry was not identified.

PMID- 16409909
TI  - Inflammatory vitiligo with raised borders and psoriasiform histopathology.

PMID- 16409910
TI  - Tuberculous gluteal abscess coexisting with scrofuloderma and tubercular
      lymphadenitis.
AB  - A 23-year-old man presented with diffuse swelling of the left buttock with
      overlying skin lesions associated with seropurulent discharge. There was no past
      history of tuberculosis. Routine investigations were normal and smears of the
      discharge for bacteria, fungi, and AFB were negative. However, culture of skin
      biopsy showed Mycobacterium tuberculosis. Skin and lymph node biopsy showed
      granulomatous inflammation suggestive of tuberculosis. Administration of
      antitubucular therapy led to complete resolution of the lesions within 12 months.

PMID- 16409911
TI  - Congenital erythropoietic porphyria in two siblings.
AB  - Congenital erythropoietic porphyria is a very rare autosomal recessive disease,
      with mutation in the gene that codifies uroporphyrinogen-III synthetase, leading
      to porphyrin accumulation in many tissues, with marked skin photosensitivity. Two
      male siblings, aged 43 and 29, are described. The oldest shows severe
      sclerodermiform mutilation and the youngest exhibits initial involvement with
      hypertrichosis. Laboratory investigation shows polycythemia, increased urine
      uroporphyrins and coproporphyrins and increased erythrocyte porphyrins.

PMID- 16409912
TI  - Merkel cell tumor and chronic lymphocytic leukemia--coincidence or a possible
      association?

PMID- 16409913
TI  - Hereditary papulotranslucent acrokeratoderma: a case report and literature
      review.
AB  - Hereditary papulotranslucent acrokeratoderma is a rare autosomal-dominant
      syndrome of the hands and feet characterized by persistent, asymptomatic,
      yellowish to white papules and plaques associated with fine-textured scalp hair
      and an atopic diathesis. Histopathologically, focal hyperkeratosis,
      hypergranulosis, and acanthosis of the epidermis are seen. We present a case of
      hereditary papulotranslucent acrokeratoderma in a young adult woman. The
      literature of this unusual condition is reviewed, and its relationship to
      acquired papulotranslucent acrokeratoderma is discussed.

PMID- 16409914
TI  - Actinomycosis: a rare soft tissue infection.
AB  - Actinomycosis is a chronic and suppurative infection caused by an endogenous Gram
      positive bacterium. The usual sites of infection are the head and neck, thorax,
      and abdomen. Primary cutaneous actinomycosis is very rare and usually associated
      with external trauma and local ischemia. We report on the case of a primary
      cutaneous actinomycosis of the thigh in a 34-year-old man. The patient was
      treated successfully with surgical resection and combined antibiotic therapy, and
      eventually cutaneous reconstructive surgical procedure.

PMID- 16409915
TI  - Cutaneous small-vessel vasculitis with unexpected circulating and in situ bound
      pemphigus autoantibodies.
AB  - Pemphigus or pemphigus-related autoantibodies have been found in sera of patients
      with diverse diseases, such as toxic epidermal necrolysis, thermal burns, and
      penicillin reactions. Here we report a patient with a typical cutaneous
      necrotizing vasculitis in whom immunofluorescence studies revealed the presence
      of circulating and tissue-bound pemphigus autoantibodies.

PMID- 16409916
TI  - Cytological diagnosis of subcutaneous fat necrosis of newborn: a case report.
AB  - Cytological findings of subcutaneous fat necrosis of the newborn, a rare and
      transient disorder of neonates, is described in a 20-day-old male baby, who
      presented with a 2-week history of firm, erythematous nodules and plaques on the
      back and upper arms.

PMID- 16409917
TI  - Sustained effects of low dose infliximab in combination with methotrexate in the
      management of chronic recalcitrant psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease whose pathogenesis is modulated
      by numerous genetic and immunologic factors. During the last decade, our
      understanding of the pathophysiology of psoriasis has significantly improved, and
      the disease is now accepted as a T-cell mediated process. This concept has
      dramatically altered the approach to the treatment of psoriasis. Tumor necrosis
      factor-alpha (TNF-alpha) is one of the key chemokines in the pathophysiology of
      psoriasis and its expression is notably increased in psoriatic plaques.
      Infliximab is a chimeric anti-TNF-alpha monoclonal antibody that binds to both
      transmembrane and soluble TNF-alpha with high affinity, specificity, and avidity.
      Presented here is a severe recalcitrant case of psoriasis with sustained benefit
      from low-dose infliximab in combination with methotrexate.

PMID- 16409918
TI  - Genital primary herpetic infection in an infant: clinical features, diagnosis and
      management.
AB  - Genital herpes is a rare disease in infants and is mainly associated with herpes
      simplex virus (HSV) type 1. Asymptomatic carriers are frequently implicated as
      transmitters of the disease. Clinical manifestations are the main criteria for
      diagnosis, However, type-specific serologies and PCR are the most sensitive
      techniques for detecting HSV. Genital herpes is treated with local or systemic
      antiviral therapy depending on the severity of the infection. Reducing
      transmission relies on counseling patients. The disease prognosis is correlated
      with the underlying immunological status. We report a case of genital primary
      herpetic infection in an infant.

PMID- 16409919
TI  - Alopecia areata in Darier disease and clinical findings in five affected family
      members.
AB  - A 32-year-old man known to have keratosis follicularis presented with a new
      problem of alopecia areata involving his scalp. His Darier disease had been
      present for 24 years and was manifested by pruritic eruptions that were more
      severe in the summer months. Other family members, including his father, brother,
      and two sisters suffered from similar skin manifestations.

PMID- 16409920
TI  - Cellulitis-like fixed drug eruption attributed to paracetamol (acetaminophen).
AB  - Paracetamol (acetaminophen) is a widely used analgesic-antipyretic with
      consistent safety profile and very low incidence of side effects. We report a
      case of biopsy-confirmed fixed drug eruption associated with paracetamol and
      presenting like cellulitis.

PMID- 16409921
TI  - Non-pigmented fixed drug eruption induced by eprazinone hydrochloride.
AB  - A 68-year-old woman developed an upper respiratory tract infection in November
      2002 and was treated with eprazinone hydrochloride, serrapeptase, carbocysteine
      and clarithromycin. Three days after the start of treatment, the patient noted
      erythema on her axilla, buttock and inguinal regions. The erythema subsided in 7
      days although slight pigmentation remained. However, 7 days later the
      pigmentation completely disappeared. Oral eprazinone hydrochloride was given as a
      challenge, and 1 day later the erythema re-appeared in the same areas as on
      initial presentation (axilla, buttock, and inguinal regions). A fixed erythema
      without lasting pigmentation is attributed to eprazinone hydrochloride.
      Therefore, the patient was diagnosed as having a nonpigmented fixed drug eruption
      associated with eprazinone hydrochloride.

PMID- 16409922
TI  - Dermatomal vesicular eruption in an asymptomatic infant.
AB  - We present a case of infantile herpes zoster without clinical evidence of
      varicella infection in the mother or apparent exposure in the child; our
      patient's diagnosis was confirmed by serology and by Tzanck smear. We briefly
      review the etiopathogenesis factors of this condition. We emphasize the benign
      course and spontaneous uneventful resolution.

PMID- 16409923
TI  - Histiocytoses.
AB  - Histiocytoses are a heterogeneous group of disorders that are not clearly
      understood. The unifying aspect of the entire spectrum lies in the accumulation
      of histiocytes in various tissues. Two cases are being presented for their rarity
      and the importance of histological features and marker studies in the diagnosis
      is emphasized.

PMID- 16409924
TI  - Aplasia cutis congenita: a case report.
AB  - Aplasia cutis congenita is a rare anomaly presenting with absence of skin. The
      most common site is the scalp. No definite etiology is available. Heredity is
      proposed with not much evidence. We present an instance with ACC occurring in
      both mother and son, suggesting a hereditary etiology.

PMID- 16409925
TI  - Old World eyelid cutaneous leishmaniasis: a case report.
AB  - Leishmania is a protozoa that may infect the skin, mucous, and viscera. The
      geographical distribution of cutaneous leishmaniasis (CL) is mainly determined by
      the sandfly vectors. The Old World type is mainly attributed to Leishmania major
      and Leishmania tropica, and in South of Europe only to Leishmania infantum. A 63
      year-old woman, who noted a pimple on the external third of the left upper eyelid
      6 months before. The lesion was nodular, well-defined and measured 1.1 cm in
      diameter and in height, simulating a basal cell carcinoma. It was surgically
      excised. CL diagnosis was made upon the histologic examination, which showed
      histiocytes with intracellular leishmania organisms. At 2 years followup, no
      evidence exists of cutaneous, mucous, or visceral involvement. Apart from
      carcinomas, nodular lesions with central ulceration are rare on the eyelid. A
      single cutaneous lesion of leishmania (oriental sore) has to be considered in the
      differential diagnosis, along with malignant eyelid neoplasms.

PMID- 16409927
TI  - Febrile ulceronecrotic Mucha-Habermann disease: a case report and a review of the
      literature.
AB  - We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a
      27-year-old woman. After 20 days of a mild eruption, extensive polymorphous,
      papular and ulcerohemorrhagic skin lesions gradually developed, associated with
      intermittent high temperature, and constitutional symptoms. The initial treatment
      with acyclovir was not successful, the skin lesions still progressed distally and
      individual lesions evolved from necrotic papules and bullae to erosions and
      ulcers. Skin biopsies showed the typical histopathological changes of PLEVA. The
      patient was treated with systemic prednisolone but dosage was limited in order to
      avoid sepsis. Despite corticosteroid therapy and supportive therapy, the
      fulminating course led to death. Including this present case, only 31 cases of
      FUMHD have been reported in English literature. Our case is the second report
      from Turkey.

PMID- 16409926
TI  - Repigmentation in vitiligo universalis: role of melanocyte density, disease
      duration, and melanocytic reservoir.
AB  - Recent reports suggest that vitiligo lesions are not totally devoid of
      melanocytes. We report an interesting observation made in the vitiliginous skin
      of an Indian patient being treated for pemphigus vulgaris with dexamethasone
      cyclophosphamide pulse therapy. Our observations indicate that melanocytes are
      never completely absent in the depigmented epidermis and that these melanocytes
      can recover their functionality in vivo and in vitro under an appropriate
      stimulus.

PMID- 16409928
TI  - [Thoracic interscapular resection for basal cell carcinoma: report of a case].

PMID- 16409929
TI  - Segmental neurofibromatosis of face.
AB  - A 38-year-old man presented with asymptomatic skin lesions over the left side of
      the face of 5-years duration. He had multiple discrete soft-to-firm papules and
      nodules on the left side of the face along the distribution of the mandibular
      division of the trigeminal nerve. Histopathology examination of one of the
      nodules (face) showed a non-encapsulated tumor of the dermis with normal
      overlying epidermis. The tumor consisted of loosely spaced spindle cells and wavy
      collagenous strands in a clear matrix. These features were consistent with our
      clinical diagnosis of segmental neurofibromatosis. This case is reported for its
      rarity and typical manifestations.

PMID- 16409930
TI  - Eruptive syringomas.
AB  - Eruptive syringoma is a rare clinical presentation of a benign tumor of the
      eccrine ducts. It consists in successive crops of small skin-colored papules on
      the anterior body surfaces. It generally occurs in the peri-pubertal period.
      Treatment of this benign condition is cosmetic only. A case of a 19-year-old
      female with a 5-year history of eruptive syringoma is presented.

PMID- 16409931
TI  - Brain abscesses with pemphigus vulgaris: a rare association.
AB  - Pemphigus is a rare group of skin disorders characterized by blistering because
      of loosening of desmosomal links between epidermal cells attributed to
      immunological attack. Pemphigus vulgaris is characterized by the presence of the
      split within the epidermis just above the basal layers (suprabasal). Central
      nervous system complications of the disorder have scantily been described in the
      English literature. We report what we believe to be the first case of cerebral
      abscesses in a 38-year-old male associated with pemphigus vulgaris and
      immunosuppressive therapy.

PMID- 16409932
TI  - Ichthyosis follicularis with congenital atrichia, nail dystrophy and palmoplantar
      keratoderma. Variant of IFAP syndrome or a new entity?
AB  - A 23-year-old man was seen for dry, rough skin and alopecia present since birth.
      There was no history of impaired sweating, photophobia, or lacrimation.
      Examination revealed generalized cutaneous thorn-like projections with
      nonscarring alopecia, twenty-nail dystrophy, and palmoplantar keratoderma.

PMID- 16409933
TI  - Median raphe cyst of the penis.
AB  - Cysts of the median raphe are uncommon. We describe a 43-year-old man with an
      asymptomatic nodule on the glans penis. Excision of the lesion was performed
      followed by histological and immunohistochemical studies. Histopathological
      examination revealed a solitary unilocular cystic cavity in the corium, lined by
      a pseudostratified columnar epithelium, among which mucinous cells where
      identified. Hints of decapitation secretion occurred at the apex of the luminal
      layer. An immunohistochemical study using a standard avidin-biotin peroxidase
      method disclosed CK7 and CK13 reactivity in the columnar cells. Epithelial
      membrane antigen (EMA) and carcinoembryonic (CEA) antigen immunoreactivity
      occurred at the apical border of the luminal cells. No staining was obtained with
      anti-CK20, human milk fat globulin 1 (HMFG1) and anti- S100 protein. The study
      supports its histogenetic relationship with the urothelium.

PMID- 16409934
TI  - Discoid lupus erythematosus in an infant.
AB  - Discoid lupus erythematosus (DLE) is rare in childhood. We report the case of a
      15-month-old female infant who presented with erythematous telangectatic lesions
      and photosensitivity involving the sun-exposed areas. Histological examination
      confirmed the diagnosis of DLE. Direct immunofluorescence (DIF) on lesional skin
      showed granular IgM deposits along basement membrane zone. Laboratory tests were
      normal. External photo-protection and topical corticosteroids lead to complete
      healing. Summer recurrences that responded to topical corticosteroids were noted
      but there was no progression to systemic lupus erythematosus. Several authors
      note the absence of female predominance in children with DLE; prevalence of
      photosensitivity is controversial. Histological confirmation of DLE is easy and
      important for diagnosis. DIF is not specific but can be helpful in establishing
      the diagnosis of DLE. Laboratory tests rarely show low titers of antinuclear
      antibodies. Treatment is based on sun avoidance and photoprotection. Topical
      corticosteroids are indicated for active lesions. For resistant cases
      antimalarials are the treatment of choice. Progression to SLE is probably more
      frequent in children than in adults.

PMID- 16409935
TI  - Penetration enhancers improve therapeutic effectiveness of topical
      immunomodulators.

PMID- 16409936
TI  - Reports of immunologic reactions to imiquimod: an assessment of actinic keratoses
      and treatment concerns in this era of litigation lotto.

PMID- 16409937
TI  - Pseudovitiligo in Systemic Sclerosis.
AB  - Progressive Systemic Sclerosis is a chronic connective tissue disease
      characterized by sclerosis of skin with involvement of the internal organs. The
      cause of PSS is unknown but autoimmune mechanisms and primary damage to blood
      vessels have been proposed to explain its pathogenesis. We report a case of PSS
      with widespread depigmentation resembling vitiligo.

PMID- 16409938
TI  - Topiramate and scars.
AB  - Topiramate may be a safe and effective treatment for scars. Shapira et al.
      reported an open label study on ten adult subjects with discolored or raised
      scars at least 2 years old who were given topiramate in an oral dosage of 15 mg
      per day for 1 month. The dosage was then increased to 30 mg per day if there was
      minimal or no improvement. Based on that study, BDC Research Centre treated 91
      patients with various scarring conditions including post acne, varicella,
      dermatitis scars, melasma, hypertrophic scars, and keloids. Excellent to good
      results were observed in post-acne and post-varicella scars.

PMID- 16409939
TI  - Systemic Lupus Erythematosus (SLE) presenting with peripheral neuropathy: a rare
      occurrence.

PMID- 16409940
TI  - Relationship between ABO blood groups and skin cancers.
AB  - Studies of associations between various cancers and the ABO blood groups have
      shown elevated relative risks for some categories of disease. To date, no report
      has evaluated the relationship between the ABO blood groups and the skin cancers.
      To investigate this association, we conducted a retrospective study of
      premalignant and malignant tumors diagnosed in Turkey. All tumors were
      histologically confirmed. Blood information was obtained for 98 individuals with
      premalignant and malignant skin tumors, and the distribution of ABO and Rh blood
      type for cases was compared with that of 419 healthy blood donors from the same
      geographic area. Although patients with blood group A were higher, group 0 lower
      than in controls, the differences were not significant. The distribution of Rh
      factor, blood group B and AB among cases and controls also did not differ
      significantly. We found a significant relationship between age and skin cancer
      (p=0.0001). Old patients had 1.238 times higher risk for skin cancer. Further
      studies in larger series on blood group antigens are needed to elucidate the
      relationship between these antigens and skin cancer.

PMID- 16409941
TI  - Urticaria and large cell undifferentiated carcinoma of lung.
AB  - The association of urticaria with internal cancer is known mostly with
      lymphoreticular system malignancies. Rarely, it occurs with cancer of lung,
      mostly with adenocarcinoma or small cell carcinoma. We report a unique occurrence
      of urticaria on a patient who suffered from large cell undifferentiated carcinoma
      of lung. Only the treatment for malignancy relieved the patient from his long
      standing cutaneous manifestation.

PMID- 16409942
TI  - Oral lesions of syphilis: an isolated, rare manifestation.

PMID- 16409943
TI  - [Predictive value of chest pain score for the diagnosis of acute coronary
      syndromes].
AB  - BACKGROUND AND OBJECTIVE: We analyzed the diagnostic utility of a chest pain
      score in patients evaluated for chest pain of possible coronary origin. PATIENTS
      AND METHOD: We studied 1,068 consecutive patients coming to the emergency room
      with acute chest pain of possible coronary origin without ST-segment elevation,
      using a chest pain unit protocol. Chest pain was quantified by validated score (0
      20 points). The diagnostic value of the chest pain score was analyzed for the
      diagnosis of acute myocardial infarction (AMI), unstable angina (UA) and acute
      coronary syndrome (ACS; AMI or UA). RESULTS: The diagnosis of ACS was established
      in 651 patients (61%), AMI in 439 (41%) and UA in 212 (20%). In the multivariate
      analysis a chest pain score > or = 10 was an independent predictor of ACS (odds
      ratio [OR] = 2.9; 95% confidence interval [CI] 2.1-4; p = 0.0001), along with an
      age older than 70 years (OR = 2.6; 95% CI,1.8-3.7; p = 0.0001), male gender (OR =
      2; 95% CI, 1.4-2.8; p = 0.0001); insulin-dependent diabetes (OR = 2.3; 95% CI,
      1.2-4.6; p = 0.016); previous myocardial infarction (OR = 1.6; 95% CI, 1.1-2.4; p
      = 0.022), ST depression (OR = 9.3; 95% CI, 5.2-16.7; p = 0.0001) and T wave
      inversion (OR = 2.5; 95% CI, 1.4-4.3; p = 0.0001). The chest pain score was
      associated with the diagnosis of both AMI (OR = 1.4; 95% CI, 1.1-1.9; p < 0.02)
      and UA (OR = 2.8; 95% CI, 1.8-4.2; p < 0.0001). CONCLUSIONS: The chest pain score
      allows independent information for the early diagnosis of patients coming to the
      emergency department with acute chest pain of possible coronary origin.

PMID- 16409944
TI  - [Population-based incidence of lymphoid neoplasms by histological subtypes in
      Girona (Spain), 1994-2001].
AB  - BACKGROUND AND OBJECTIVE: We aimed to assess the distribution of the lymphoid
      neoplasms and their histological subtypes in accordance with the World Health
      Organization (WHO) classification by calculating their incidences rates in our
      area. PATIENTS AND METHOD: From January 1994 to December 2001, 1,288 patients
      diagnosed with lymphoid neoplasms were recruited in the population-based Cancer
      Registry of Girona. Former pathological and hematological diagnoses were reviewed
      and some were prospectively reclassified following the latest WHO classification.
      RESULTS: Following criteria established by WHO classification the distribution of
      lymphoid neoplasms was as follows: 77.3% B-cell neoplasm, 5.9% T-cell neoplasm,
      8.7% Hodgkin lymphoma and 8,2% was unclassifiable. From 1994 TO 2001 the lymphoid
      neoplasm crude incidence rates was 35.8 per 100,000 men-year, while it was 25.7
      new cases per 100,000 women-year. In children (< 15 years old), precursor B
      lymphoblastic lymphoma/leukemia (65%) and Hodgkin lymphoma (20%) were the most
      frequent lymphoid neoplasm, whereas myeloma (17.8%), diffuse large B-cell
      lymphoma (13.5%) showed the highest incidence rate in adults. CONCLUSIONS: A
      higher incidence rate of lymphoid neoplasms was found in men in our area compared
      with other geographical areas in Spain, which could suggested a faster
      approximation to the pattern observed in industrialized societies. The cause of
      this geographical distribution is unknown.

PMID- 16409945
TI  - [Estimation of the excess of lung cancer mortality risk associated to
      environmental tobacco smoke exposure of hospitality workers].
AB  - BACKGROUND AND OBJECTIVE: To estimate the excess lung cancer mortality risk
      associated with environmental tobacco (ETS) smoke exposure among hospitality
      workers. The estimation was done using objective measures in several hospitality
      settings in Barcelona. METHOD: Vapour phase nicotine was measured in several
      hospitality settings. These measurements were used to estimate the excess lung
      cancer mortality risk associated with ETS exposure for a 40 year working life,
      using the formula developed by Repace and Lowrey. RESULTS: Excess lung cancer
      mortality risk associated with ETS exposure was higher than 145 deaths per
      100,000 workers in all places studied, except for cafeterias in hospitals, where
      excess lung cancer mortality risk was 22 per 100,000. In discoteques, for
      comparison, excess lung cancer mortality risk is 1,733 deaths per 100,000
      workers. CONCLUSION: Hospitality workers are exposed to ETS levels related to a
      very high excess lung cancer mortality risk. These data confirm that ETS control
      measures are needed to protect hospital workers.

PMID- 16409946
TI  - [Chest pain: a diagnostic and prognostic challenge].

PMID- 16409947
TI  - [Environmental tobacco smoke in the workplace].

PMID- 16409948
TI  - [Obesity and bariatric surgery: from last resort to first election therapy].

PMID- 16409949
TI  - [Travel advice for special travellers].
AB  - The increase in the hope and quality of life, along with the greater rapidity and
      comfort of the different means of transport have made possible that travellers
      with chronic diseases, pregnant and kids makes tourist trips to tropical or
      subtropical zones. On the other hand the increase of the international
      cooperation has caused the appearance of long stay travellers who live in
      conditions such as the local population. These travellers have special
      characteristics due to their physical training conditions, chronic treatments, or
      the way of life during the travel that them makes more susceptible to suffer
      problems of health during the travel. For this reason the usual recommendations
      for travellers are insufficient in these groups and is necessary to make an
      individualized travel advice that considers these factors. This revision shows
      the most important warnings that must be made in these groups of special
      travellers.

PMID- 16409951
TI  - [Influenza outbreaks in highly-vaccinated older institutionalised people in the
      2004-2005 season].

PMID- 16409950
TI  - [Medium-long term treatment with infliximab and methotrexate in posterior and/or
      chronic uveitis refractory to conventional treatment].

PMID- 16409952
TI  - [Epistaxis and nifedipine].

PMID- 16409953
TI  - [Managing the patient with multimorbidity in a hospital at home unit].

PMID- 16409954
TI  - [Patients with multimorbidity in a Internal Medicine Department].

PMID- 16409955
TI  - [Public reporting of advances in medicine: a shared responsibility].

PMID- 16409957
TI  - [Orthostatic hypotension in the 2005 Spanish guidelines on arterial hypertension:
      a proposal standardization of the method of diagnosis].

PMID- 16409958
TI  - [Methodological quality assessment of clinical trials in traditional Chinese
      medicine: the principles of evidence-based medicine].
AB  - The quality of clinical trials in traditional Chinese medicine (TCM) was analyzed
      with respect to their methodology and outcome assessment according to the
      concepts of evidence-based medicine (EBM). It was suggested that the essential
      methodological principles of EBM should be applied in clinical trials of TCM,
      including randomization, control and blindness. The sample size estimation,
      optimal parameter selection for outcome assessment, compliance and intention-to
      treat analysis are all important aspects of randomized controlled trials. To
      bring the benefits of EBM into clinical trials will improve the quality of
      research in TCM and also promote international co-operation and communications.
      It is necessary to establish an assessment system of clinical outcome for TCM on
      the basis of EBM in order to evaluate the efficacy and safety of TCM objectively
      and scientifically.

PMID- 16409959
TI  - [Potential effects of the methods for warming yang and nourishing yin on long
      term prognosis of chronic heart failure].
AB  - Warming yang, which is one of the treatment principles of traditional Chinese
      Medicine, is very important in treating chronic heart failure, especially late
      stage heart failure. It has been proved in many experiments and clinical trials
      that warming yang can improve the hemodynamic parameters. The treatment strategy
      for heart failure has changed from short-term correction of hemodynamic
      parameters to long-term rehabilitation approaches. We discussed the possible
      negative-effects of warming yang on neuroendocrine responses and myocardial
      remodeling. The potential beneficial effects of treatment for nourishing yin or
      nourishing yin combined with warming yang on heart failure were also explored.

PMID- 16409960
TI  - [Relationship between female ages and the theory of five tones correlated with
      five zang viscera in Huangdi Neijing].
AB  - OBJECTIVE: To find out some evidence that may indicate the theory of voice pitch
      of the five tones being correlated with the five zang viscera in Huangdi Neijing,
      which was lost 2 000 years. METHODS: Eight-four healthy females were divided into
      younger group (<34 years old) and older group (> or =34 years old) according to
      their ages. The pronunciations of these females were examined by sono-frequency
      analysis facility. RESULTS: The frequency of Jiao tone was much higher than those
      of the other tones in both groups (P<0.01) and the frequency of Jiao tone
      increased as aging. The frequency of Zhi tone in the younger group was higher
      than that in the older group (P<0.05). CONCLUSION: The results of higher
      frequency of Jiao tone in females is in accordance with the theory put forward by
      Ye Gui (a famous doctor in Qing Dynasty of China) that the liver is the
      congenital base of female life. In traditional Chinese medicine, Jiao tone is
      correlated with the liver, and Zhi tone is correlated with the heart. The high
      frequency of Zhi tone in younger females implies that regulating the Small
      Intestine Meridian of Hand-Taiyang and Heart Meridian of Hand-Shaoyin may be
      beneficial to the health maintenance of younger female.

PMID- 16409961
TI  - [Comparative study on normal tongue manifestation in patients with primary liver
      cancer and healthy adults].
AB  - OBJECTIVE: To find out some microscopically visible morphological differences in
      normal tongue manifestation between patients with primary liver cancer and
      healthy adults, and provide some beneficial evidences for microcosmic syndrome
      differentiation of tongue inspection. METHODS: Microcirculations of the tongue
      tip, which represented the macroscopical normal tongue manifestation, were
      observed under an optical microscope in patients with primary liver cancer and
      healthy adults. Exfoliated cells from tongue coating were examined by hematoxylin
      eosin staining. RESULTS: The proportion of normal tongue manifestation was larger
      in healthy adults (38.89%) than that in patients with primary liver cancer
      (2.32%). The total score of microcirculation of tongue tip and the maturation
      index of exfoliated cells from tongue coating were both higher in patients with
      primary liver cancer than those in healthy adults with normal tongue
      manifestation (P<0.01, P<0.05). CONCLUSION: Normal tongue manifestation, which is
      macroscopically visible, can be observed in both patients with primary liver
      cancer and healthy adults, but there exists obvious difference in microcosmic
      view.

PMID- 16409962
TI  - [Clinical study on severe acute pancreatitis complicated by hepatic
      insufficiency].
AB  - OBJECTIVE: To investigate the pathogenic factors of severe acute pancreatitis
      (SAP) complicated by hepatic insufficiency, the prognosis and the effective
      preventive and therapeutic interventions. METHODS: One hundred and fifty-two
      patients with SAP (from January 2003 to June 2004) were divided into 2 groups,
      SAP with hepatic insufficiency group and SAP without hepatic insufficiency group.
      The related factors such as causes of disease, serum biochemical criteria,
      complications, mortality and course of disease were observed. RESULTS: The
      concentrations of serum amylase, creatinine and lactate dehydrogenase were all
      much higher in the SAP with hepatic insufficiency group than those in the SAP
      without hepatic insufficiency group (P<0.05). The incidences of complications
      such as acute renal failure, heart failure, gastrointestinal hemorrhage and
      infection were also higher in the SAP with hepatic insufficiency group than those
      in the SAP without hepatic insufficiency group (P<0.05). There was no significant
      difference in mortality between these two groups, but the course of disease in
      SAP with hepatic insufficiency group was longer than that in the other group
      (P<0.05). CONCLUSION: The causes of SAP complicated by hepatic insufficiency are
      related to the imbalance of internal environment and the characteristics of the
      liver function. To control the biliary tract diseases, intervene with traditional
      Chinese medicine, recover the intestinal function in time, reduce the damage of
      pancreatic enzyme, maintain the stability of internal environment and avoid using
      drugs that can induce liver injury are all important aspects of reducing the
      incidence of hepatic insufficiency.

PMID- 16409963
TI  - [Evaluation on methodological problems in reports concerning quantitative
      analysis of syndrome differentiation of diabetes mellitus].
AB  - OBJECTIVE: To evaluate the quality of reports published in recent 10 years in
      China about quantitative analysis of syndrome differentiation for diabetes
      mellitus (DM) in order to explore the methodological problems in these reports
      and find possible solutions. METHODS: The main medical literature databases in
      China were searched. Thirty-one articles were included and evaluated by the
      principles of clinical epidemiology. RESULTS: There were many mistakes and
      deficiencies in these articles, such as clinical trial designs, diagnosis
      criteria for DM, standards of syndrome differentiation of DM, case inclusive and
      exclusive criteria, sample size and estimation, data comparability and
      statistical methods. CONCLUSION: It is necessary and important to improve the
      quality of reports concerning quantitative analysis of syndrome differentiation
      of DM in light of the principles of clinical epidemiology.

PMID- 16409964
TI  - [Efficacy of modified acupotome combined with blocking therapy in patients with
      carpal tunnel syndrome].
AB  - OBJECTIVE: To observe the efficacy of modified acupotome combined with blocking
      therapy in patients with carpal tunnel syndrome (CTS). METHODS: Fifty-five
      patients with CTS were divided into three groups, which were modified acupotome
      group including 26 CTS patients with 28 lesions treated by modified acupotome
      combined with blocking therapy, traditional acupotome group including 14 CTS
      patients with 16 lesions treated by traditional acupotome combined with blocking
      therapy, and blocking therapy group including 15 CTS patients with 15 lesions
      only treated by local blocking. The treatment outcome and one-year recurrence
      rate were observed. RESULTS: The response rate and one-year recurrence rate after
      operation in the modified acupotome group were 85.7% (24/28) and 20.8% (5/24)
      respectively, which had no significant differences as compared with 81.3% (13/16)
      and 38.5% (5/13) in the traditional acupotome group. The response rate and one
      year recurrence rate after operation in the above two groups were both improved
      significantly as compared with those in the blocking therapy group which were
      46.7% (7/15) and 85.7% (6/7) respectively. There were no acupotome-related
      adverse effects and injuries observed in the modified acupotome group.
      CONCLUSION: The modified acupotome is a considerable treatment method for CTS
      with respect to its simple manipulation and high effectiveness.

PMID- 16409965
TI  - [Effects of recipe for invigorating kidney on expression of estrogen receptors in
      ovariectomized rats].
AB  - OBJECTIVE: To observe the effects of recipe for invigorating kidney on expression
      of estrogen receptors in ovariectomized rats. METHODS: The rats, which were given
      high-cholesterol diet after ovariectomy, were chosen as experimental subjects.
      After fed kidney-invigorating recipe for 16 weeks, the rats were killed and the
      levels of serum lipid and estradiol of these rats were examined. The expressions
      of estrogen receptor alpha and beta mRNAs in aorta, pituitary gland and
      hypothalamus, and the affinity of estrogen receptor-ligand were also detected.
      RESULTS: The kidney-invigorating recipe could increase the expression levels of
      estrogen receptor alpha and beta mRNAs in different parts such as aorta,
      pituitary gland and hypothalamus, and enhance the affinity of estrogen receptor
      ligands. CONCLUSION: The recipe for invigorating kidney may meliorate
      atherosclerosis in ovariectomized rats by regulating the estrogen receptors.

PMID- 16409966
TI  - [Effects of active components extracted from Qixue Bingzhi Recipe on
      proliferation of vascular smooth muscle cells and expressions of platelet-derived
      growth factor and its receptor genes].
AB  - OBJECTIVE: To observe the effects of paeoniflorin and total flavones extracted
      from Qixue Bingzhi Recipe on proliferation of vascular smooth muscle cells
      (VSMCs) cultured in endothelial cell conditioned medium (EC-CM) induced by
      oxidized low-density lipoprotein (ox-LDL) and the expressions of platelet-derived
      growth factor and its receptor genes. METHODS: The VSMCs were cultured in normal
      culture medium, EC-CM, simvastatin-medicated EC-CM, paeoniflorin and total
      flavones (low, medium and high dose) -medicated EC-CM respectively. The growth
      activity of VSMCs was assessed by thiazolyl blue tetrazolium bromide (MTT) assay.
      The expressions of platelet-derived growth factor (PDGF)-BB and platelet-derived
      growth factor receptor-alpha (PDGFR-alpha) mRNAs were detected by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: The growth activity of
      VSMCs cultured in the EC-CM induced by ox-LDL was significantly higher than that
      in the normal culture medium (P<0.01), and the expressions of PDGF-BB and PDGFR
      alpha mRNAs were obviously increased as compared with those in the normal culture
      medium. The growth activity of VSMCs cultured in each paeoniflorin and total
      flavones-medicated EC-CM was significantly lower than that in the EC-CM (P<0.01),
      and the expressions of PDGF-BB and PDGFR-alpha mRNAs were obviously decreased as
      compared with those in the EC-CM. CONCLUSION: The paeoniflorin and total flavones
      extracted from Qixue Bingzhi Recipe may be beneficial to the prevention and
      treatment of arteriosclerosis, and this efficacy may be correlated with down
      regulating the expressions of PDGF-BB and PDGFR-alpha mRNAs which are related to
      the proliferation of VSMCs cultured in EC-CM induced by ox-LDL.

PMID- 16409967
TI  - [Effects of tetramethylpyrazine on fibrosis of atrial tissue and atrial
      fibrillation in a canine model of congestive heart failure induced by ventricular
      tachypacing].
AB  - OBJECTIVE: To explore the effects of tetramethylpyrazine (TMP) on fibrosis of
      atrial tissue and atrial fibrillation in a canine model of congestive heart
      failure (CHF) induced by ventricular tachypacing. METHODS: Twenty-one healthy
      mongrel dogs were randomly divided into three groups, which were normal control
      group, untreated group and TMP-treated group. Atrial fibrillation (AF) was
      induced by burst of atrial pacing, after the canine model of CHF was established.
      The atrial tissues were sampled and stained with Mallory's trichromic stains,
      then the fibrosis in the atrial tissues was analyzed. The left ventricular
      ejection fraction (LVEF) was evaluated by echocardiography. The levels of
      angiotensin II (AngII), aldosterone (ALD), amino-terminal peptide of type III
      procollagen (PIIINP)ilaminin (LN) and hyaluronic acid (HA) in peripheral blood
      were examined by radioimmunoassay. RESULTS: The LVEF was significantly decreased
      in the untreated group as compared with that in the normal control group
      (P<0.01), while the frequencies of AF and sustaining AF were significantly
      increased and the AF duration was obviously prolonged in the untreated group as
      compared with those in the normal control group (P<0.01). The fibrosis degree in
      the left or right atrial tissue in the untreated group was more serious than that
      in the normal control group (P<0.01). The AF duration was positively correlated
      with the fibrosis degree in the left atrial tissue (r=0.84, P=0.018). The levels
      of AngII, ALD, PIIINP and HA in peripheral blood were significantly higher in the
      untreated group than those in the normal control group (P<0.05 or P<0.01). The
      level of AngII was positively correlated with the level of ALD in peripheral
      blood (r=0.759, P=0.048). The LVEF and the frequency of sustaining AF were both
      significantly improved in the TMP-treated group as compared with those in the
      untreated group (P<0.05). The fibrosis in the left or right atrial tissue in the
      untreated group was more serious than that in the untreated group (P<0.01). The
      levels of AngII and PIIINP in peripheral blood were also markedly higher in the
      TMP-treated group than those in the untreated group (P=0.05, P=0.01). CONCLUSION:
      Tetramethylpyrazine has the effect of reducing the fibrosis degree of atrial
      tissue in dogs with CHF, and this efficacy may be related to the mechanism of
      decreasing the frequency of AF and shortening the AF duration.

PMID- 16409968
TI  - [Signal transduction mechanism of curcumin in inhibiting the proliferation of
      bovine lens epithelial cell induced by recombinant human epidermal growth
      factor].
AB  - OBJECTIVE: To investigate the signal transduction mechanism of curcumin in
      inhibiting the proliferation of bovine lens epithelial cell (LEC) induced by
      recombinant human epidermal growth factor (rhEGF). METHODS: There were three
      groups in this experiment, which were normal control group, untreated group and
      curcumin-treated group. Proliferation of LEC was induced by rhEGF (50 microg/L).
      The concentration of intracellular Ca(2+) ([Ca(2+)](i)) in LEC was measured with
      Fura-2/AM by spectrofluorimetry. The contents of intracellular cAMP and cGMP were
      assayed by radioimmunoassay. RESULTS: The [Ca(2+)]i in LEC was obviously
      increased in the untrated group as compared with that in the normal control group
      (P<0.01), and the [Ca(2+)](i) in LEC in the curcumin-treated group was highest
      among three groups (P<0.01). The content of intracellular cAMP in LEC was
      decreased while the content of intracellular cGMP was obviously increased in the
      untreated group as compared with those in the normal control group (P<0.01). The
      content of intracellular cAMP in LEC was higher in the curcumin-treated group
      than that in the untreated group, while the content of intracellular cGMP was
      lower than that in the untreated group (P<0.01). CONCLUSION: The
      antiproliferation effects of curcumin on LEC may relate to the regulations of
      multiple processes of signal transduction.

PMID- 16409969
TI  - [Effects of Tangshenling Mixture and benazepril on rats with diabetic nephropathy
      and its mechanism].
AB  - OBJECTIVE: To investigate the effects of Tangshenling Mixture (TSLM) and
      benazepril on rats with diabetic nephropathy (DN) and its mechanism. METHODS:
      Diabetic nephropathy was induced in rats by intraperitoneal injection of
      streptozotocin. Fifty-eight rats with DN were randomly divided into four groups:
      untreated group, TSLM-treated group, TSLM plus benazepril-treated group and
      benazepril-treated group. Another seven normal rats were included in normal
      control group. Then, rats in each group were accordingly given normal saline,
      TSLM, TSLM plus benazepril and benazepril orally for six weeks respectively.
      Blood and urine biochemical indexes, plasma atrial natriuretic factor (ANF),
      pathomorphology of renal tissue, transforming growth factor beta1 (TGF-beta1) and
      glucose transporter 1 (GLUT1) mRNAs in renal tissue were observed. RESULTS: Both
      TSLM and benazepril could decrease urinary albumin excretion rates, creatinine
      clearance and ratio of kidney weight to body weight of the rats with DN as well
      as reduce the pathological damages of the renal tissues. TSLM could reduce the
      level of plasma ANF and the expression of GLUT1 mRNA, but had no significant
      effect on the expression of TGF-beta1 mRNA. Benazepril could reduce the
      expression of TGF-beta1 mRNA, but had no significant effect on plasma ANF and the
      expression of GLUT1 mRNA. CONCLUSION: TSLM can reduce the pathological damages of
      renal tissues in rats with early-stage DN, and its mechanism may relate to
      decreasing the level of plasma ANF and the expression of GLUT1 mRNA which is
      different from that of benazepril. It seems that TSLM has synergetic effect with
      benazepril.

PMID- 16409970
TI  - [Effects of Naohuandan Recipe on learning and memory abilities of SAM-P/8 mice
      and its role in anti-oxidation and anti-apoptosis].
AB  - OBJECTIVE: To investigate the effects of Naohuandan Recipe on learning and memory
      abilities of SAM-P/8 mice and its role in anti-oxidation and anti-apoptosis.
      METHODS: Forty SAM-P/8 mice were randomly divided into four groups, which were
      untreated (normal saline-treated) group, Yinkeluo Tablets (extracts of gingko
      leaf)-treated group, low-dose Naohuandan Recipe-treated group and high-dose
      Naohuandan Recipe-treated group. Mice in these groups were given corresponding
      drugs orally for 105 days. Then the performances of learning and memory of mice
      were tested by a step-down passive avoidance task and a Y-maze test. The serum
      levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione
      peroxidase (GSH-Px) were detected. The expression level of bcl-xl mRNA in
      cerebral cortex and hippocampus of mice was detected by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: The performances of learning and
      memory in the Yinkeluo Tablets-treated group, low- and high-dose Naohuandan
      Recipe-treated groups were significantly improved as compared with those in the
      untreated group (P<0.05 or P<0.01), and such performance was the best in the high
      dose Naohuandan Recipe-treated group among these four groups (P<0.01). The serum
      levels of SOD and GSH-Px and the expression of bcl-xl mRNA in cerebral cortex and
      hippocampus of mice in the Yinkeluo Tablets-treated group, low- and high-dose
      Naohuandan Recipe-treated groups were also significantly higher than those in the
      untreated group (P<0.05 or P<0.01), while the serum level of MDA in the untreated
      group was higher than that in the other three groups (P<0.01). CONCLUSION:
      Naohuandan Recipe can improve learning and memory abilities of SAM-P/8 mice, and
      this effect may be related to its anti-oxidation efficacy and enhancement of
      expression level of bcl-xl mRNA.

PMID- 16409971
TI  - [Arnebia root oil promotes wound healing and expression of basic fibroblast
      growth factor on the wound surface in rabbits].
AB  - OBJECTIVE: To observe the promoting effect of arnebia root oils on expression of
      basic fibroblast growth factor (bFGF) in skin wound of rabbits and the
      histomorphological changes in the wound surface, and to discuss its mechanism.
      METHODS: Bilateral round skin wounds were made on the back of 15 rabbits. The
      three wounds on one side of the back of each rabbit were treated with arnebia
      root oils, while the three wounds on the other side were treated with vaseline in
      order to promote the wound healing. The histomorphology and ultrastructure under
      electron microscopy of the wounds, and the rate of wound healing were examined at
      different time. Western blotting assay was used to detect the expression of bFGF
      in the wound surface. RESULTS: The healing rate of the arnebia root oils-treated
      wounds was evidently higher than that of the vaseline-treated wounds (P<0.05).
      The quantities of fibroblast, collagen and capillary in the arnebia root oils
      treated wounds were much more than those in the vaseline-treated wounds, and the
      expression of endogenous bFGF in the arnebia root oils-treated wounds was
      enhanced obviously as compared with that in the vaseline-treated wounds in
      different period of wound healing. There existed a parallel correlation between
      the expression level of bFGF and the rate of wound healing. CONCLUSION: The
      promoting effect of arnebia root oils on wound healing may be related to
      increasing the expression level of basic fibroblast growth factor in the skin
      wound.

PMID- 16409972
TI  - [Inhibiting effects of recipe for dispersing stagnated liver qi to promote bile
      flow on cholesterol gallstone formation in guinea pigs].
AB  - OBJECTIVE: To explore the mechanism of the inhibiting effects of recipe for
      dispersing stagnated liver qi to promote bile flow (Danshijing Tablets) on
      cholesterol gallstone formation and provide experimental evidence for its
      clinical application. METHODS: Eighty guinea pigs were randomly divided into 4
      groups, which were normal control group, untreated group, ursodeoxycholic acid
      (UDCA)-treated group and Danshijing Tablets-treated group. The gallstones in
      guinea pigs were induced by high-cholesterol diet. UDCA and Danshijing Tablets
      were given orally to guinea pigs in the corresponding group respectively for
      seven weeks. Then the physical signs of the guinea pigs, the rates of gallstone
      formation and the histomorphological changes of the gallbladder were examined.
      RESULTS: The behavior of guinea pigs in the Danshijing Tablets-treated group was
      obviously improved and the rate of gallstone formation was significantly
      decreased as compared with those in both untreated and UDCA-treated groups
      (P<0.05). The inflammation reaction of mucous membrane in gallbladder was
      evidently reduced in the Danshijing Tablets-treated group and its morphological
      appearance turned to be approximately normal. CONCLUSION: Recipe for dispersing
      stagnated liver qi to promote bile flow may decrease gallstone formation. Its
      mechanism may be related to reducing pathologic changes in gallbladder tissues,
      which will reduce the damages of cholesterol to the smooth muscle in gallbladder
      and enhance the contractility of gallbladder.

PMID- 16409973
TI  - [Effects of herb therapy for benefiting qi and removing blood stasis on
      ultrastructure of vascular endothelial cells and vascular smooth muscle cells of
      uterine endometrium in rabbits with copper intrauterine device].
AB  - OBJECTIVE: To observe the effects of herb therapy for benefiting qi and removing
      blood stasis on ultrastructure of vascular endothelial cells (VECs) and vascular
      smooth muscle cells (VSMCs) of uterine endometrium in rabbits with copper
      intrauterine device. METHODS: Fifty-six rabbits were randomly divided into seven
      groups, which were normal control group, sham-operation group, untreated group,
      indomethacin-treated group and low-, medium- and high-dose Gonghuan Zhixueling
      Recipe (GHZXLR)-treated groups. The rabbits in the last five groups were operated
      with copper IUD insertion and then orally given distilled water, indomethacin and
      low-, medium- and high-dose GHZXLR respectively for at least one week. Rabbits in
      the normal control group and sham-operation group were given distilled water
      orally. The ultrastructure of VECs and VSMCs of uterine endometrium in rabbits
      was observed by transmission electron microscopy. RESULTS: The morphological
      changes of VSMCs revealed intracellular edema, organelle disintegration and
      decrease of organelle amount, or cell atrophy and vacuolar degeneration of
      mitochondria in the untreated group, and the amount of collagen fibers also
      increased outside the VSMCs. Local interstitial edema in subendothelial substance
      and vacuolar degeneration of mitochondria in VECs were both observed. The
      ultrastructural damages to the mitochondria, Golgi bodies and myofilament of VECs
      and VSMCs and the intercellular substance in GHZXLR-treated groups were slighter
      than those in the untreated group, while these damages had no significant
      differences as compared with those in the indomethacin-treated group. CONCLUSION:
      The Chinese herb therapy for benefiting qi for removing blood stasis has the
      protective effect on VECs of uterine endometrium in the rabbits with copper
      intrauterine device. It appears to be a good treatment for menorrhagia induced by
      copper IUD insertion.

PMID- 16409974
TI  - [High-throughput screening assay for groups of effective components extracted
      from Xiaoxuming Recipe].
AB  - OBJECTIVE: To present a new approach for the research of effective components
      extracted from compounds of traditional Chinese medicine and their action
      mechanisms by high-throughput screening assay. METHODS: We observed the anti
      oxidation activities of 240 sequential components (L1-L120 and A1-A120) extracted
      from Xiaoxuming Recipe, the effects of these components on SH-SY5Y cells with
      H(2)O(2)-induced and L-glutamic acid-induced damages and the levels of resting
      calcium ion in neurocytes of rats. RESULTS: Some components (L1-L40, A100-A120)
      extracted from Xiaoxuming Recipe had the corresponding effects listed above. The
      combination of these components was regarded as the groups of effective
      components of Xiaoxuming Recipe in treating sequelae resulting from brain
      ischemia. CONCLUSION: Xiaoxuming Recipe has protective effect on brain-ischemia
      induced damages through the actions of multiple components with multiple targets.

PMID- 16409975
TI  - [Percutaneous absorption of aconitine and mesaconitine in extracts of Radix
      Aconitum kusnezoffii].
AB  - OBJECTIVE: This study was conducted to evaluate the percutaneous absorption of
      aconitine and mesaconitine in extracts of Radix Aconitum kusnezoffii. METHODS:
      The extracts of Radix Aconitum kusnezoffii were collected by using Franz
      diffusion cells after permeation through the skin of rats. Then rate constants of
      skin permeation of aconitine and mesaconitine were determined by high-performance
      liquid chromatography (HPLC). RESULTS: Under the condition that the
      concentrations of azone and propylene glycol were both 4%, the cumulative doses
      of skin permeation (Q) of mesaconitine and aconitine in the extracts of Radix
      Aconitum kusnezoffii (600 mg/ml) for 24 hours were 165.819 and 487.747
      microg/cm(2) respectively, and their rate constants of skin permeation were
      18.391 and 78.805 microg.cm(-2).h(-1) respectively. CONCLUSION: The aconitine and
      mesaconitine in the extracts of Radix Aconitum kusnezoffii can penetrate well
      through the skin of rats. Propylene glycol and azone can promote this penetration
      effects. The formula of skin permeation of mesaconitine and aconitine is in
      accordance with Higuchi equation and there is a linear relationship between Q and
      t(1/2).

PMID- 16409976
TI  - [Effects of electroacupuncture treatment on nitrergic neurotransmitter in bladder
      neck and detrusor of rats with unstable bladder].
AB  - OBJECTIVE: To observe the effects of electroacupuncture treatment on nitrergic
      neurotransmitter in bladder neck and detrusor of rats with unstable bladder.
      METHODS: Rat models of unstable bladder were established by operation to induce
      urethral obstruction. Electroacupuncture treatment was given by acupuncturing
      Huiyang and Zhonglushu points for a week. Then the neuronal nitric oxide synthase
      (nNOS)-, endothelial nitric oxide synthase (eNOS)- and inducible nitric oxide
      synthase (iNOS)-positive cells in bladder neck and detrusor of the rats were
      observed. RESULTS: The nitrergic neurotransmitter in bladder neck and detrusor
      were obviously decreased in rats with unstable bladder. The electroacupuncture
      treatment could significantly increase the contains of NOS in bladder tissue.
      CONCLUSION: To promote the synthesis and secretion of nitrergic neurotransmitter
      in bladder tissue may be one of the mechanisms of acupuncture in adjusting
      bladder function.

PMID- 16409977
TI  - [Effects of manipulation on head repositioning skill in patients with cervical
      vertigo].

PMID- 16409978
TI  - [Effects of Matrine Injection on T-lymphocyte subsets of patients with malignant
      tumor after gamma knife radiosurgery].

PMID- 16409979
TI  - [Clinical observation of puerarin in treating patients with vertebral artery
      insufficiency due to cervical spondylosis: a report of 123 cases].

PMID- 16409980
TI  - [Treatment of severe scapulohumeral periarthritis with combined use of
      suprascapular nerve blockade and manipulation therapy: a report of 49 cases].

PMID- 16409982
TI  - [Analysis of characteristics of acupuncture-moxibustion treatment for limb tremor
      in ancient China].

PMID- 16409981
TI  - [Clinical study on treatment of malignant neoplasms with Shenqi Fuzheng Injection
      and chemotherapy].

PMID- 16409983
TI  - [Experience in clinical practice of doctrines in Huangdi Neijing: Part 2].

PMID- 16409984
TI  - [Application of primary culture technique to traditional Chinese medicine
      research].

PMID- 16409985
TI  - [Hypoxia-inducible factor-1 and its correlation with removing blood stasis for
      promoting tissue regeneration of traditional Chinese principle of treatment].

PMID- 16409986
TI  - [Progress in research on antitumor activity of saikosaponin and its mechanism].

PMID- 16409987
TI  - [On methodology in English translation of traditional Chinese medicine].

PMID- 16409988
TI  - [Definition criteria for subject of English translation of traditional Chinese
      medicine].

PMID- 16409989
TI  - [Pondering the problems and development of English translation for traditional
      Chinese medicine].

PMID- 16409990
TI  - Expression Analysis Systematic Explorer (EASE) analysis reveals differential gene
      expression in permanent and transient focal stroke rat models.
AB  - To gain greater insight on the molecular mechanisms that underlie ischemic
      stroke, we compared gene expression profiles in transient (tMCAO) and permanent
      middle cerebral artery occlusion (pMCAO) stroke models using Expression Analysis
      Systematic Explorer (EASE) pathway analysis software. Many transcripts were
      induced in both stroke models, including genes associated with transcriptional
      pathways, cell death, stress responses and metabolism. However, EASE analysis of
      the regulated genes indicated molecular functions and biological processes unique
      to each model. Pathways associated with tMCAO included inflammation, apoptosis
      and cell cycle, while pMCAO was associated with the induction of genes encoding
      neurotransmitter receptors, ion channels, growth factors and signaling molecules.
      An intriguing finding was the involvement of tyrosine kinases and phosphatases
      following pMCAO. These results provide evidence that neuronal death following
      tMCAO and pMCAO involves distinct mechanisms. These findings may give new insight
      to the molecular mechanisms involved in stroke and may lead to novel
      neuroprotective strategies.

PMID- 16409991
TI  - Through the central V2, not V1 receptors influencing the endogenous opiate
      peptide system, arginine vasopressin, not oxytocin in the hypothalamic
      paraventricular nucleus involves in the antinociception in the rat.
AB  - Our previous study has proven that hypothalamic paraventricular nucleus (PVN)
      played a role in the antinociception. The central bioactive substances involving
      in the PVN regulating antinociception were investigated in the rat. The results
      showed that electrical stimulation of the PVN increased the pain threshold, and L
      glutamate sodium injection into the PVN elevated the pain threshold, but the PVN
      cauterization decreased the pain threshold; pain stimulation raised the arginine
      vasopressin (AVP), not oxytocin (OXT), leucine-enkephalin (L-Ek), beta-endorphin
      (beta-Ep) and DynorphinA1-13 (DynA1-13) concentrations in the PVN tissue using
      micropunch method, heightened AVP, L-Ek, beta-Ep and DynA1-13, not OXT
      concentrations in the PVN perfuse liquid, and reduced the number of AVP-, not
      OXT, L-Ek, beta-Ep and DynA1-13-immunoreactive neurons in the PVN especially in
      the posterior magnocellular part of the PVN using immunocytochemistry. There was
      a negative relationship between the PVN AVP concentration and the pain threshold;
      pain stimulation enhanced the AVP, not OXT mRNA expression in the PVN using in
      situ hybridization and RT-PCR; intraventricular injection of anti-AVP serum
      completely reversed L-glutamate sodium injection into the PVN-induced
      antinociception, and administration of naloxone - the opiate peptide antagonist,
      partly blocked this L-glutamate sodium effect, but anti-OXT serum pretreatment
      did not influence this L-glutamate sodium effect; L-glutamate sodium injection
      into the PVN-induced analgesia was inhibited by V2 receptor antagonist -
      d(CH2)5[D-Ile2, Ile4, Ala-NH2(9)]AVP, not V1 receptor antagonist -
      d(CH2)5Tyr(Me)AVP. The data suggested that the PVN was limited to the central
      AVP, not OXT, which was through V2, not V1 receptors influencing the endogenous
      opiate peptide system, to regulate antinociception.

PMID- 16409992
TI  - ERP correlates of retrieval orientation: direct versus indirect memory tasks.
AB  - The neural correlates of the processes involved in cueing memory retrieval were
      investigated using ERPs to unstudied (new) items in a yes/no recognition test
      (direct memory task) and a semantic judgement task (indirect memory task).
      Subjects encoded either pictures or auditory words and were tested on visual
      words. We replicated previous findings that ERPs to correct rejections of new
      items in a yes/no recognition test differ according to the study material, with
      ERPs to words encoded as pictures being more negative (relative to a average
      mastoid reference) than words encoded auditorily [Hornberger, M., Morcom, A.M.,
      et al., 2004. Neural correlates of retrieval orientation: effects of study-test
      similarity. J. Cogn. Neurosci. 16 (7), 1196-1210]. This difference was sustained
      from approximately 450-1,200 ms. An effect of study material on the ERP to new
      items was found in the indirect memory task but was both earlier onsetting and
      shorter lived, ca. 250-600 ms. These findings add weight to the concept of
      'retrieval orientation' [Rugg, M.D., Wilding, E.L., 2000. Retrieval processing
      and episodic memory. Trends Cogn. Sci. 4 (3) 108-115] - differential processing
      of retrieval cues according to the form of the sought-for information - by
      showing that a putative ERP correlate of retrieval orientation is restricted to
      direct memory tasks.

PMID- 16409993
TI  - De novo and salvage pathways of DNA synthesis in primary cultured neurall stem
      cells.
AB  - We studied the de novo and salvage pathways of DNA synthesis in sphere-forming
      neural stem cells obtained from mouse embryos by a neurosphere method. The former
      pathway needs folic acid (FA) for nucleotide biosynthesis, while the latter
      requires deoxyribonucleosides (dNS). We examined the proliferative activity of
      sphere-forming cells in E14.5 embryos by counting the number of spheres formed in
      media that lacked FA and/or dNS. Proliferation failure and apoptosis occurred in
      a deficient medium lacking of both FA and dNS. Spheres formed in the deficient
      medium supplemented with dNS, without FA, did not produce neuron, but rather only
      seem to generate astrocytes and oligodendrocytes when plated under
      differentiation condition in culture. On the other hand, a subpopulation of
      cultured cells formed spheres in the deficient medium supplemented with FA alone
      in an appropriate concentration, and did possess the self-renewing and
      multipotential characteristics of neural stem cells. Spheres formed in the media
      containing low dose Azathioprine and methotrexate, inhibitors of de novo DNA
      synthesis, were selectively prevented from producing neurons even in the presence
      of FA. These results suggested that activating de novo DNA synthesis was needed
      for neural stem cells to proliferate with multipotentiality.

PMID- 16409994
TI  - Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in
      rat striatum.
AB  - The present study investigated the role of lysosomal enzymes in excitotoxic
      neuronal damage induced by excessive stimulation of non-NMDA glutamate receptors
      with kainic acid (KA). Internucleosomal DNA fragmentation was induced after
      intrastriatal administration of KA 1.25-5.0 nmol to rats. Increased expression of
      cathepsin B (P < 0.01, n = 6) but not cathepsin L in KA-injected striatum was
      observed 12 to 24 h after intrastriatal infusion of KA (2.5 nmol). Treatment with
      intrastriatal infusion of the cathepsin B inhibitor Z-FA-FMK (5-10 microg) 10 min
      prior to or 3 h after KA injection robustly attenuated KA-induced (2.5 nmol) DNA
      fragmentation. Z-FA-FMK (10 microg) also significantly reduced the size of
      striatal lesions induced by KA (P < 0.01, n = 6). These results suggest that
      lysosomal enzyme cathepsin B plays an important role in excitotoxic neuronal
      injury.

PMID- 16409995
TI  - Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or
      tolerance: evidence for multiple diverse hyperalgesic systems.
AB  - Hyperalgesia following chronic morphine treatment is thought to be a response to
      opioid receptor activation and analgesia and contribute to the development of
      analgesic tolerance. Here, the relationship between these variables was studied
      in mice tested for nociceptive sensitivity on the tail-withdrawal test during
      chronic infusion of various morphine doses. Hyperalgesic onset was preceded by
      dose-dependent analgesia except for the lowest morphine dose, which caused
      hyperalgesia 6 h after the start of infusion. Morphine ED50 values obtained at
      various infusion intervals demonstrated both analgesic tolerance in the absence
      of hyperalgesia and hyperalgesia in the absence of tolerance. Continuous opioid
      receptor antagonism using naltrexone pellets abolished analgesia during
      continuous morphine administration, transiently potentiated hyperalgesia, and
      revealed differences in hyperalgesic onset between morphine infusion doses. Acute
      injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801
      attenuated hyperalgesia in naltrexone-treated mice, demonstrating a role for this
      receptor in morphine hyperalgesia unrelated to its effects upon morphine
      analgesia. In mice where hyperalgesia subsided after continuous infusion of the
      highest morphine dose (i.e., hyperalgesic adaptation), hyperalgesia was restored
      after infusing the lower but not higher morphine dose. In addition, acute
      injection of morphine-3beta-glucoronide (M3G) caused hyperalgesia that was cross
      adaptive with the lower morphine dose only. The data demonstrate that morphine
      hyperalgesia is independent of prior or concurrent opioid receptor activity or
      analgesia and is unrelated to analgesic tolerance. Furthermore, the lack of
      hyperalgesic cross-adaptation between high and low morphine doses, and their
      differential cross-adaptation with M3G hyperalgesia, also suggests distinct
      morphine dose-dependent hyperalgesic systems.

PMID- 16409996
TI  - Efficacy of systemic administration of SDF-1 in a model of vascular
      insufficiency: support for an endothelium-dependent mechanism.
AB  - OBJECTIVE: Studies have reported that administration of stromal cell-derived
      factor-1 (SDF-1), the ligand for the G-protein coupled receptor CXCR4, increased
      collateral blood flow in a mouse model of vascular insufficiency via recruitment
      of endothelial precursor cells (EPC). The present study investigated the
      contribution of mature endothelial cells in the actions of SDF-1. METHODS: The
      regulation of SDF-1 and CXCR4 was examined in the rat cornea cauterization (CC)
      and aortic ring (AR) model. The functional significance of the SDF-1/CXCR4
      pathway was explored in cultured endothelial cells, the AR model, and on
      collateral blood flow in a rat model of vascular insufficiency. RESULTS: In the
      present study, the CXCR4 transcript was dramatically upregulated in the rat CC
      and AR explants, systems containing and lacking bone marrow-derived EPCs,
      respectively. Addition of AMD3100, a selective CXCR4 antagonist, had no effect on
      vessel growth in the AR alone, but completely inhibited SDF-1 mediated increases
      in vascular sprouting. In cultured endothelial cells, SDF-1 alone or in
      combination with vascular endothelial growth factor (VEGF) significantly enhanced
      cell survival and migration. Finally, systemic administration of SDF-1 in a rat
      model of arterial insufficiency enhanced collateral blood flow above vehicle
      control and equal to that of VEGF after 2 weeks of treatment. CONCLUSION: These
      studies support activation of the SDF-1/CXCR4 axis as a means to promote blood
      vessel growth and enhance collateral blood flow, at least in part, via direct
      effects on vascular endothelial cells.

PMID- 16409997
TI  - Fibulin-2 is present in murine vascular lesions and is important for smooth
      muscle cell migration.
AB  - OBJECTIVE: The vascular extracellular matrix (ECM) can affect smooth muscle cell
      (SMC) adhesion, migration and proliferation-events that are important during the
      atherosclerotic process. Fibulin-2 is a member of the ECM protein family of
      fibulins and has been found to cross-link versican/hyaluronan complexes, an ECM
      network that has been suggested to be important during tissue repair. In this
      study we have analysed the presence of fibulin-2 in two different models of
      murine vascular lesions. We have also examined how the fibulin-2/versican network
      influences SMC migration. METHODS: Presence of fibulin-2 was analysed by
      immunohistochemistry in atherosclerotic aortas and in mechanically injured
      carotid arteries from mice. Fibulin-2 protein levels were also studied by Western
      blotting during rat aortic SMC phenotypic modulation in vitro. The importance of
      a fibulin-2/versican interaction for SMC migration was studied in the presence of
      two inhibiting peptides (FN III 3-5 and aggrecan C-type lectin-like domain).
      RESULTS: Fibulin-2 is expressed in SMC rich regions of atherosclerotic lesions
      where it colocalises with versican and hyaluronan. It is also present in injury
      induced vascular lesions and is upregulated during SMC phenotypic modulation in
      cell culture. Moreover, treatments with peptides that block the interaction
      between versican and fibulin-2 inhibit SMC migration in vitro. CONCLUSIONS:
      Fibulin-2 can be produced by SMC as a response to injury and may participate in
      the ECM organisation that regulates SMC migration during vessel wall repair.

PMID- 16409998
TI  - Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced
      expressions.
AB  - Ocular angiogenesis may lead to visual impairment and even irreversible blindness
      in people of all ages worldwide. Choroidal neovascularization (CNV), a major
      clinical complication of ocular angiogenesis, is an important cause of vision
      loss that affects a large number of people. Physiological angiogenesis is tightly
      controlled by a balance in the expression of angiogenic and anti-angiogenic
      factors. While the underlying mechanism of CNV is complex, it is attributed to an
      upset in this balance. The vascular endothelial growth factor (VEGF) is essential
      in the development of CNV as one of the most potent angiogenic stimulators and
      vascular permeability factors. Pigment epithelium derived factor (PEDF) is a
      strong inhibitor of angiogenesis with high neuroprotective effects. VEGF and PEDF
      both possess multiple biological activities and functions that affect a large
      variety of tissue cells of the eye and other organs. Inappropriate expression
      levels are associated with many diseases involving neovascularization. This paper
      describes the unbalanced expressions of VEGF and PEDF as a cause of CNV. Based on
      the respective angiogenic and anti-angiogenic properties of VEGF and PEDF,
      experimental models have been devised to genetically reduce VEGF or enhance PEDF
      to achieve therapeutic effects. Gene therapy for CNV is promising and is under
      intensive research.

PMID- 16409999
TI  - Cocaine-induced increases in medial prefrontal cortical GABA transmission
      involves glutamatergic receptors.
AB  - A recent study showed that cocaine-induced sensitization is associated with an
      increase in GABA (gamma-aminobutyric acid) transmission in the medial prefrontal
      cortex. Since previous studies have demonstrated that sensitization is associated
      with enhanced medial prefrontal cortex glutamatergic transmission, the present
      study examined the role of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptors in cocaine-induced
      increases in medial prefrontal cortex GABA levels. Male Sprague-Dawley rats
      received four daily injections of saline (1 ml/kg, i.p.) or cocaine (15 mg/kg).
      One day later, animals were infused with NMDA or AMPA/KA antagonists 3-[(R)-2
      carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and 6,7-dinitroquinoxaline
      2,3-dione (DNQX), respectively, into medial prefrontal cortex via microdialysis
      probe for 60 min before receiving systemic challenge injections of saline or
      cocaine. Cocaine-sensitized animals showed an increase in extracellular medial
      prefrontal cortex GABA levels that was blocked by prior medial prefrontal cortex
      infusion of DNQX, but not CPP. These data indicate that enhanced medial
      prefrontal cortex GABA transmission seen in cocaine-sensitized animals involves
      glutamatergic stimulation of AMPA receptors.

PMID- 16410000
TI  - Angiotensin II-induced vasodilatation in cerebral arteries is mediated by
      endothelium-derived hyperpolarising factor.
AB  - The angiotensin II-induced vasodilatation was evaluated in rat middle cerebral
      artery, especially regarding endothelium-derived hyperpolarising factor (EDHF),
      by use of a pressurised arteriograph. The angiotensin II dilatation was partly
      antagonised by inhibitors of nitric oxide synthase and cyclo-oxygenase. The
      remaining dilatation was inhibited by the potassium channel blockers,
      charybdotoxin and apamin, providing direct evidence that angiotensin II induces
      EDHF-mediated dilatation in cerebral arteries. The angiotensin II dilatation was
      blocked by the angiotensin AT1 and AT2 receptor blockers candesartan and PD
      123319. Both angiotensin AT1 and AT2 receptors were detected on the endothelium
      by immunohistochemistry.

PMID- 16410002
TI  - Different mechanisms may generate sustained hypertonic and rhythmic bursting
      muscle activity in idiopathic dystonia.
AB  - Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi)
      is emerging as the favored intervention for patients with medically intractable
      dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In
      eight patients with primary dystonia who were treated with bilateral chronic
      pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity
      of the most affected muscles with the local field potentials (LFPs) recorded from
      the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary
      movements, rhythmic EMG bursts in the contralateral muscles were coherent with
      the oscillations in the pallidal LFPs at the burst frequency. In contrast, no
      significant coherence was seen between EMG and LFPs either for the sustained
      activity separated out from the compound EMGs in those 5 cases, or in the EMGs in
      3 other cases without mobile involuntary movements and rhythmic EMG bursts. In
      comparison with the resting condition, in both active and passive movements,
      significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The
      finding of significant coherence between GPi oscillations and rhythmic EMG bursts
      but not sustained tonic EMG activity suggests that the synchronized pallidal
      activity may be directly related to the rhythmic involuntary movements. In
      contrast, the sustained hypertonic muscle activity may be represented by less
      synchronized activity in the pallidum. Thus, the pallidum may play different
      roles in generating different components of the dystonic symptom complex.

PMID- 16410001
TI  - Coxsackievirus and adenovirus receptor (CAR) is expressed in male germ cells and
      forms a complex with the differentiation factor JAM-C in mouse testis.
AB  - The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein
      important for viral binding to target cells. Using RT-PCR, Western analysis, GST
      pull-down assay and indirect immunofluorescence, it was shown that CAR is
      expressed in male germ cells from mice, rats, and humans. CAR was detected in
      round spermatids in the testis as well as in purified, mature spermatozoa. The
      two membrane-bound isoforms of CAR occupied different subcellular sites in the
      acrosomal region of the spermatozoa. CAR was exposed on the surface of acrosome
      reacted, but not acrosome-intact cells. Two CAR-binding proteins belonging to the
      ligand-of-numb protein-X (LNX) family also occupied distinct regions in
      spermatozoa. Finally, co-immunoprecipitation experiments demonstrated an
      interaction between CAR and JAM-C, a protein required for spermatid
      differentiation. Together, these findings imply a function for CAR in male
      fertility. The results also suggest that CAR in spermatozoa is inaccessible to
      adenovirus-based gene therapy vectors, and that the risk of germ line infection
      therefore is low.

PMID- 16410003
TI  - Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances
      muscle function in Mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease due to
      a mutation in the dystrophin gene and the consequential protein deficiency in
      muscle. How the lack of the sarcolemmal protein dystrophin gives rise to the
      final disease status is still not clear. Several evidences suggest a role of
      nuclear factor kappa-B (NF-kappaB), a pleiotropic transcription factor, in muscle
      degeneration and regeneration in DMD patients and mdx mice. We investigated the
      effects of NF-kappaB blocking by pyrrolidine dithiocarbamate (PDTC), a well-known
      NF-kappaB inhibitor, on dystrophic process in mdx mice. Five-week-old mdx and
      wild-type mice received three times a week for 5 weeks either PDTC (50 mg/kg) or
      its vehicle. PDTC treatment: (i) increased forelimb strength (+20%; P < 0.05) and
      strength normalized to weight (+24%; P < 0.05) and a decreased fatigue percentage
      (-61%; P < 0.05) in mdx mice, (ii) blunted the augmented NF-kappaB nuclear
      binding activity and the enhanced TNF-alpha expression in dystrophic muscles (P <
      0.01), (iii) at a quantitative morphological evaluation of extensor digitorum
      longus (EDL) and biceps muscles, increased area with normal fibers (P < 0.05, in
      EDL), reduced muscle necrosis (P < 0.05 in biceps; P < 0.01 in EDL), and enhanced
      muscle regeneration (P < 0.01, in biceps). Our data support the hypothesis that
      NF-kappaB contributes to the perpetuation of the dystrophic damage and show that
      its blockade produces beneficial effects on functional, biochemical, and
      morphological parameters in mdx mice. Most importantly, these new findings may
      have clinical implications for the pharmacological treatment of patients with
      DMD.

PMID- 16410004
TI  - Oligodendrocyte progenitor cell (OPC) transplantation is unlikely to offer a
      means of preventing X-irradiation induced damage in the CNS.
AB  - Oligodendrocyte lineage cells [oligodendrocytes and their parent cells, the
      oligodendrocyte progenitor cells (OPCs)] are depleted by X-irradiation and
      progenitor cell transplantation has been proposed as a therapeutic strategy to
      counteract radiation induced myelopathy. Previous studies have demonstrated that
      oligodendrocyte progenitor cell (OPC) depletion is a prerequisite for
      establishing transplanted OPCs in normal tissue. One can therefore predict that
      the extent and timing of OPC depletion and regeneration following X-irradiation
      will be crucial factors in determining the feasibility of this therapeutic
      approach. To address this issue, we have examined the time course of OPC
      depletion and regeneration following a range of X-irradiation doses (5 to 40 Gy),
      and its relationship to establishing transplanted OPCs in X-irradiated tissue.
      Doses above 10 Gy resulted in rapid death of OPCs. With doses up to 20 Gy,
      surviving X-irradiated OPCs were capable of robust regeneration, restoring normal
      densities within 6 weeks. Transplanted OPCs could only be established in tissue
      that had been exposed to > or =20 Gy. Since 20 Gy is close to the ED50 for
      radiation necrosis, our findings demonstrate the limitation of OPC replacement
      strategies.

PMID- 16410005
TI  - Angiostrongylus cantonensis: efficacy of albendazole-dexamethasone co-therapy
      against infection-induced plasminogen activators and eosinophilic meningitis.
AB  - Angiostrongyliasis is one of the common causes leading to eosinophilic
      meningitis. Tissue-type plasminogen activator (tPA) and urokinase-type
      plasminogen activator (uPA) may play a role in the pathogenesis. Administration
      of steroid drugs has been reported to possibly relieve the symptoms of
      eosinophilic meningitis. This study evaluates the curative effects of albendazole
      dexamethasone co-therapy on eosinophilic meningitis in BALB/c mice. Assay
      indicators for the therapeutic effect include worm recovery, histopathological
      score of meningitis, tPA, uPA, total protein, and leukocyte counts. The results
      show that the albendazole-dexamethasone co-therapy significantly decreased
      (P<0.05) these factors after treatment on day 5 post-inoculation (PI), in
      contrast to treatment on 15 PI. Thus, the timing of medication is important and
      is closely related to the anthelmintic efficacy of a drug. At the same dosage and
      days post-infection, the earlier administration shows better results. This study
      showed that albendazole-dexamethasone co-therapy is an effective approach for the
      treatment of parasitic meningitis.

PMID- 16410006
TI  - Phylogenetic analysis of the glucose-6-phosphate isomerase gene in Trypanosoma
      cruzi.
AB  - Trypanosoma cruzi, the agent of Chagas disease, has a basically clonal population
      structure with rare hybridization events. The species is subdivided into six
      "Discrete Typing Units" called DTUs I, IIa-e, distributed into two major
      phylogenetic lineages, T. cruzi I and II (TC I and II). The glucose-6-phosphate
      isomerase (Gpi) is a specific isoenzymic locus that presents homozygous profiles
      for DTUs I, IIa-c, and typical heterozygous patterns, for DTUs IId and IIe. The
      gene was sequenced in 12 T. cruzi stocks and in three stocks pertaining to
      related species. The phylogenetic relationships observed confirm that the DTUs I,
      IIa-c do constitute monophyletic groups. Nevertheless, the phylogenetic hierarchy
      of the DTUs is not clearly resolved with the GPI gene. The hybrid status of DTUs
      IId and IIe was clearly supported. Sequence analysis revealed that the allele 4
      present in both DTUs IIa and IIc, previously considered as unique, displayed in
      fact two distinct sequences, specific for each DTU. The level of recombination
      between alleles has been investigated.

PMID- 16410007
TI  - The corticotropin-releasing factor system as a mediator of the appetite
      suppressing effects of stress in fish.
AB  - A characteristic feature of the behavioural response to intensely acute or
      chronic stressors is a reduction in appetite. In fish, as in other vertebrates,
      the corticotropin-releasing factor (CRF) system plays a key role in coordinating
      the neuroendocrine, autonomic, and behavioural responses to stress. The following
      review documents the evidence implicating the CRF system as a mediator of the
      appetite-suppressing effects of stress in fish. Central injections of CRF or the
      related peptide, urotensin I (UI), or pharmacological treatments or stressors
      that result in an increase in forebrain CRF and UI gene expression, can elicit
      dose-dependent reductions in food intake that are at least partially reversed by
      pre-treatment with a CRF receptor antagonist. In addition, the appetite
      suppressing effects of various environmental, pathological, physical, and social
      stressors are associated with elevated levels of forebrain CRF and UI gene
      expression and with an activation of the hypothalamic-pituitary-interrenal (HPI)
      stress axis. In contrast, although stressors can also be associated with an
      increase in caudal neurosecretory system CRF and UI gene expression and an
      endocrine role for CRF-related peptides has been suggested, the physiological
      effects of peripheral CRF-related peptides on the gastrointestinal system and in
      the regulation of appetite have not been investigated. Overall, while CRF and UI
      appear to participate in the stress-induced changes in feeding behaviour in fish,
      the role of other know components of the CRF system is not known. Moreover, the
      extent to which the anorexigenic effects of CRF-related peptides are mediated
      through the hypothalamic feeding center, the HPI axis and cortisol, or via
      actions on descending autonomic pathways remains to be investigated.

PMID- 16410008
TI  - Detection of three single nucleotide polymorphisms in the gene encoding mannose
      binding lectin in a single pyrosequencing reaction.
AB  - Mannose-binding lectin (MBL) is a key molecule of innate immunity. Binding of MBL
      to carbohydrates present on pathogens activates the lectin pathway of complement
      activation, resulting into opsonization and anti-microbial protection. Three
      frequently occurring single nucleotide polymorphisms (SNPs) are described in the
      coding region of the MBL2 gene that are associated with abnormal polymerization
      of the MBL molecule, decreased serum concentrations of high molecular weight MBL,
      and strongly impaired function. Clinical studies have shown that these MBL SNPs
      are associated with increased susceptibility to infections, especially in immune
      compromised persons, as well as with accelerated progression of chronic diseases.
      The present study describes a novel method to detect the three major MBL SNPs by
      pyrosequencing. The close proximity of these SNPs allows their detection in one
      single pyrosequencing reaction, resulting in clearly distinguishable patterns for
      each allele combination described until now. This method can be used for the easy
      and reliable detection of MBL SNPs to identify the basis of functional MBL
      deficiency in clinical diagnostics and research.

PMID- 16410009
TI  - Comparison study of streptavidin-coated microtitration plates.
AB  - Streptavidin (SAv)-coated 96-well microtitration plates from commercial suppliers
      (six plates) and our laboratory (two plates) were tested with respect to their
      binding capacity for small and large molecules, leaching, well-to-well variation
      and immunoassay performance. The binding capacities for europium-labelled biotin
      (Eu-biotin) varied from 4.4 to above 150 pmol/well depending on the plate, and
      for biotinylated monoclonal antibody from 1.2 to 6.4 pmol/well (190-1030 ng).
      Incubation for 1 h in regular immunoassay buffer resulted in leaching of 0.6-76
      ng of SAv from unwashed wells and 0.5-60 ng from pre-washed wells. The desorbed
      quantity represented up to 3.4% of the maximal Eu-biotin binding capacity.
      Coating-related variation of 96 wells (CV% values) ranged from 1.2% to 8.0% when
      tested with respect to maximum binding capacity. Immunofluorometric assay for TSH
      as well as enzyme immunoassays for CA125 and PSA revealed immunoassay-related
      performance of the plates, regarding signal levels, variation and non-specific
      binding characteristics. Non-specific binding and variation tended to increase in
      the highest capacity plates, whereas some low capacity plates fulfilled the assay
      requirements optimally. Good performance with respect to capacity, coating
      homogeneity or leaching was not by definition reflected in the performance of two
      site heterogeneous immunoassays.

PMID- 16410010
TI  - Effect of fungal infection on the reproductive potential of aphids and their
      progeny.
AB  - The effect of infection by Pandora neoaphidis and Beauveria bassiana on the
      reproductive potential of the pea aphid, Acyrthosiphon pisum, and their progeny
      was assessed. Infection by either P. neoaphidis or B. bassiana reduced the number
      of nymphs produced within 24 h of inoculation and over the entire infection
      period compared to uninfected aphids. However, infection by either P. neoaphidis
      or B. bassiana for 24 or 72 h did not alter the intrinsic rate of increase of the
      host aphid's progeny. Therefore, fungal infection appears to have no indirect
      effects on the fitness of the host's progeny.

PMID- 16410011
TI  - Nosema chrysorrhoeae n. sp. (Microsporidia), isolated from browntail moth
      (Euproctis chrysorrhoea L.) (Lepidoptera, Lymantriidae) in Bulgaria:
      characterization and phylogenetic relationships.
AB  - A new microsporidian parasite Nosema chrysorrhoeae n. sp., isolated in Bulgaria
      from the browntail moth (Euproctis chrysorrhoea L.), is described. Its life cycle
      includes two sequential developmental cycles that are similar to the general
      developmental cycles of the Nosema-like microsporidia and are indistinguishable
      from those of two Nosema spp. from Lymantria dispar. The primary cycle takes
      place in the midgut tissues and produces binucleate primary spores. The secondary
      developmental cycle takes place exclusively in the silk glands and produces
      binucleate environmental spores. N. chrysorrhoeae is specific to the browntail
      moth. Phylogenetic analysis based on the ssu rRNA gene sequence places N.
      chrysorrhoeae in the Nosema/Vairimorpha clade, with the microsporidia from
      lymantriid and hymenopteran hosts. Partial sequences of the lsu rRNA gene and ITS
      of related species Nosema kovacevici (Purrini K., Weiser J., 1975. Naturliche
      Feinde des Goldafters, Euproctis chrysorrhoea L., im Gebiet von Kosovo, FSR
      Jugoslawien. Anzeiger fuer Schadlingskunde, Pflanzen-Umweltschutz, 48, 11-12),
      Nosema serbica Weiser, 1963 and Nosema sp. from Lymantria monacha was obtained
      and compared with N. chrysorrhoeae. The molecular data indicate the necessity of
      future taxonomic reevaluation of the genera Nosema and Vairimorpha.

PMID- 16410012
TI  - Effects of solubilization on the structure and function of the sensory rhodopsin
      II/transducer complex.
AB  - Lipid-protein interactions are known to play a crucial role in structure and
      physiological activity of integral membrane proteins. However, current technology
      for membrane protein purification necessitates extraction from the membrane into
      detergent micelles. Also, due to experimental protocols, most of the data
      available for membrane proteins is obtained using detergent-solubilized samples.
      Stable solubilization of membrane proteins is therefore an important issue in
      biotechnology as well as in biochemistry and structural biology. An understanding
      of solubilization effects on structural and functional properties of specific
      proteins is of utmost relevance for the evaluation and interpretation of
      experimental results. In this study, a comparison of structural and kinetic data
      obtained for the archaebacterial photoreceptor/transducer complex from
      Natronomonas pharaonis (NpSRII/NpHtrII) in detergent-solubilized and lipid
      reconstituted states is presented. Laser flash photolysis, fluorescence
      spectroscopy, and electron paramagnetic resonance spectroscopy data reveal
      considerable influence of solubilization on the photocycle kinetics of the
      receptor protein and on the structure of the transducer protein. Especially the
      protein-membrane proximal region and the protein-protein interfacial domains are
      sensitive towards non-native conditions. These data demonstrate that relevance of
      biochemical and structural information obtained from solubilized membrane
      proteins or membrane protein complexes has to be evaluated carefully.

PMID- 16410013
TI  - Structural basis for the requirement of two phosphotyrosine residues in signaling
      mediated by Syk tyrosine kinase.
AB  - The protein-tyrosine kinase Syk couples immune recognition receptors to multiple
      signal transduction pathways, including the mobilization of calcium and the
      activation of NFAT. The ability of Syk to regulate signaling is influenced by its
      phosphorylation on tyrosine residues within the linker B region. The
      phosphorylation of both Y342 and Y346 is necessary for optimal signaling from the
      B cell receptor for antigen. The SH2 domains of multiple signaling proteins share
      the ability to bind this doubly phosphorylated site. The NMR structure of the C
      terminal SH2 domain of PLCgamma (PLCC) bound to a doubly phosphorylated Syk
      peptide reveals a novel mode of phosphotyrosine recognition. PLCC undergoes
      extensive conformational changes upon binding to form a second phosphotyrosine
      binding pocket in which pY346 is largely desolvated and stabilized through
      electrostatic interactions. The formation of the second binding pocket is
      distinct from other modes of phosphotyrosine recognition in SH2-protein
      association. The dependence of signaling on simultaneous phosphorylation of these
      two tyrosine residues offers a new mechanism to fine-tune the cellular response
      to external stimulation.

PMID- 16410014
TI  - RNA structure and RNA-protein interactions in purified yeast U6 snRNPs.
AB  - The U6 small nuclear RNA (snRNA) undergoes major conformational changes during
      the assembly of the spliceosome and catalysis of splicing. It associates with the
      specific protein Prp24p, and a set of seven LSm2p-8p proteins, to form the U6
      small nuclear ribonucleoprotein (snRNP). These proteins have been proposed to act
      as RNA chaperones that stimulate pairing of U6 with U4 snRNA to form the
      intermolecular stem I and stem II of the U4/U6 duplex, whose formation is
      essential for spliceosomal function. However, the mechanism whereby Prp24p and
      the LSm complex facilitate U4/U6 base-pairing, as well as the exact binding
      site(s) of Prp24p in the native U6 snRNP, are not well understood. Here, we have
      investigated the secondary structure of the U6 snRNA in purified U6 snRNPs and
      compared it with its naked form. Using RNA structure-probing techniques, we
      demonstrate that within the U6 snRNP a large internal region of the U6 snRNA is
      unpaired and protected from chemical modification by bound Prp24p. Several of
      these U6 nucleotides are available for base-pairing interaction, as only their
      sugar backbone is contacted by Prp24p. Thus, Prp24p can present them to the U4
      snRNA and facilitate formation of U4/U6 stem I. We show that the 3' stem-loop is
      not bound strongly by U6 proteins in native particles. However, when compared to
      the 3' stem-loop in the naked U6 snRNA, it has a more open conformation, which
      would facilitate formation of stem II with the U4 snRNA. Our data suggest that
      the combined association of Prp24p and the LSm complex confers upon U6
      nucleotides a conformation favourable for U4/U6 base-pairing. Interestingly, we
      find that the open structure of the yeast U6 snRNA in native snRNPs can also be
      adopted by human U6 and U6atac snRNAs.

PMID- 16410015
TI  - Inhibition of protein tyrosine phosphatase activity mediates epidermal growth
      factor receptor signaling in human airway epithelial cells exposed to Zn2+.
AB  - Epidemiological studies have implicated zinc (Zn2+) in the toxicity of ambient
      particulate matter (PM) inhalation. We previously showed that exposure to metal
      laden PM inhibits protein tyrosine phosphatase (PTP) activity in human primary
      bronchial epithelial cells (HAEC) and leads to Src-dependent activation of EGFR
      signaling in B82 and A431 cells. In order to elucidate the mechanism of Zn2+
      induced EGFR activation in HAEC, we treated HAEC with 500 microM ZnSO4 for 5-20
      min and measured the state of activation of EGFR, c-Src and PTPs. Western blots
      revealed that exposure to Zn2+ results in increased phosphorylation at both trans
      and autophosphorylation sites in the EGFR. Zn2+-mediated EGFR phosphorylation
      did not require ligand binding and was ablated by the EGFR kinase inhibitor
      PD153035, but not by the Src kinase inhibitor PP2. Src activity was inhibited by
      Zn2+ treatment of HAEC, consistent with Src-independent EGFR transactivation in
      HAEC exposed to Zn2+. The rate of exogenous EGFR dephosphorylation in lysates of
      HAEC exposed to Zn2+ or V4+ was significantly diminished. Moreover, exposure of
      HAEC to Zn2+ also resulted in a significant impairment of dephosphorylation of
      endogenous EGFR. These data show that Zn2+-induced activation of EGFR in HAEC
      involves a loss of PTP activities whose function is to dephosphorylate EGFR in
      opposition to baseline EGFR kinase activity. These findings also suggest that
      there are marked cell-type-specific differences in the mechanism of EGFR
      activation induced by Zn2+ exposure.

PMID- 16410016
TI  - Characterization of the lytic-lysogenic switch of the lactococcal bacteriophage
      Tuc2009.
AB  - Tuc2009 is a temperate bacteriophage of Lactococcus lactis subsp. cremoris UC509
      which encodes a CI- and Cro-type lysogenic-lytic switch region. A helix-swap of
      the alpha3 helices of the closely related CI-type proteins from the lactococcal
      phages r1t and Tuc2009 revealed the crucial elements involved in DNA recognition
      while also pointing to conserved functional properties of phage CI proteins
      infecting different hosts. CI-type proteins have been shown to bind to specific
      sequences located in the intergenic switch region, but to date, no detailed
      binding studies have been performed on lactococcal Cro analogues. Experiments
      shown here demonstrate alternative binding sites for these two proteins of
      Tuc2009. CI2009 binds to three inverted repeats, two within the intergenic region
      and one within the cro2009 gene. This DNA-binding pattern appears to be conserved
      among repressors of lactococcal and streptococcal phages. The Cro2009 protein
      appears to bind to three direct repeats within the intergenic region causing
      distortion of the bound DNA.

PMID- 16410017
TI  - The perceived transmittance of inhomogeneous surfaces and media.
AB  - A series of experiments was performed to determine how the visual system computes
      the transmittance of inhomogeneous surfaces and media. Previous work (Anderson,
      B. L. (1999) Stereoscopic surface perception. Neuron, 26, 919-928; Anderson, B.
      L. (2003) The role of occlusion in the perception of depth, lightness, and
      opacity. Psychological Review, 110, 762-784) has suggested that the visual system
      employs a transmittance anchoring principle in determining when transparency is
      perceived. This principle states that the visual system interprets the highest
      contrast region along contours and surfaces as a region in plain view and uses
      this anchor as a reference point for transparency computations. In particular,
      recent work has shown that the transmittance of homogeneous transparent surfaces
      is well described by a ratio of contrasts model (Singh, M., & Anderson, B. L.
      (2002). Toward a perceptual theory of transparency. Psychological Review, 109,
      492-519). In this model, the transmittance of a transparent surface is determined
      by the contrast of a transparent image region normalized by the contrast of the
      region in plain view. Here, a series of experiments is reported that assesses
      this model for inhomogeneous transparent surfaces that vary in both space and
      time. The results of these experiments reveal that transmittance anchoring has
      both a spatial and temporal component, and that the perceived transmittance of
      transparent surfaces is well described by a ratio of perceived contrasts model.

PMID- 16410018
TI  - Influence of a municipal solid waste incinerator on ambient air and soil PCDD/Fs
      levels.
AB  - To examine the influence of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans (PCDD/Fs) emissions from a municipal solid waste incinerator (MSWI)
      on the environment, we measured the levels of PCDD/Fs in ambient air and soil
      samples collected near a MSWI in Bucheon, Korea. The PCDD/Fs concentrations in
      the ambient air samples ranged from 0.22 to 1.16 pg I-TEQm(-3) (13.39-75.16 pg m(
      3)), with an average of 0.66 pg I-TEQ m(-3) (35.62 pg m(-3)). The soil samples
      contained between 1.25 and 74.98 pg I-TEQ g(-1) (38.15-3,303.33 pg g(-1)), with
      an average of 19.06 pg I-TEQ g(-1) (1,077.11 pg g(-1)). These levels were higher
      than those previously reported by other investigators in a number of surveys. The
      furan homologues predominated in the air samples and some soil samples, and the
      soil PCDD/Fs levels decreased with increasing distance from the MSWI. Comparison
      of the homologue patterns and a multivariate statistical analysis showed that
      PCDD/Fs emission from the MSWI directly affected the pattern of PCDD/Fs in air,
      while the PCDD/Fs patterns in soil differed according to the location relative to
      the MSWI, roads, and construction sites. These results collectively indicate that
      the MSWI was the major PCDD/Fs emission source in this area, but that
      unidentified combustion sources and vehicles might influence the environment to
      some extent.

PMID- 16410019
TI  - Factors that influence methylmercury flux rates from wetland sediments.
AB  - Sediments are thought to be an important source of methylmercury (MeHg) to the
      water column of wetlands. We measured sediment MeHg pore water concentrations as
      a function of depth in four wetlands to determine the concentration gradient and
      used it determine sediment-water flux of MeHg. Fluxes of MeHg ranged from -1.60
      to 10.02 ng m(-2) day(-1) and were shown to be a function of 1) redox conditions
      at the sediment-water interface, 2) oxygen gradient above the sediment surface,
      3) water temperature, and 4) pore water and water column-dissolved sulphide. MeHg
      water column concentration in each of the four wetlands was positively correlated
      with MeHg concentrations present in surface sediment and pore water, and with the
      calculated sediment-water MeHg flux rate. In addition to MeHg, ethylmercury
      (EtHg) was detected in the sediment in all four wetlands, but not in the pore
      water or the water column. EtHg levels in sediment exceeded MeHg concentrations
      in two of the wetlands. This demonstrates that Hg ethylation is a significant
      part of the Hg cycle in some aquatic environments.

PMID- 16410020
TI  - Arterial antithrombotic effects of aspirin, heparin, enoxaparin and clopidogrel
      alone, or in combination, in the rat.
AB  - INTRODUCTION: Many antithrombotic drugs may have a deleterious effect on normal
      haemostasis leading to bleeding complications. The aim of this study was to
      determine if sub-therapeutic (low) doses of antithrombotic agents, when
      administered in combination, have enhanced efficacy without augmentation of
      bleeding time. MATERIALS AND METHODS: The antithrombotic effects of i.v. aspirin
      (4-30 mg/kg), heparin (100-500 U/kg), enoxaparin (4-30 mg/kg) and clopidogrel (10
      20 mg/kg) were studied in a rat Folts-like preparation of carotid arterial
      thrombosis. The frequency of cyclic flow reductions (CFRs; indicating occlusive
      thrombus formation) and bleeding time were measured. Drug doses that were singly
      ineffective at preventing occlusive thrombus formation were tested in the
      following combinations: aspirin (10 mg/kg) with heparin (250 U/kg); aspirin (4
      mg/kg) with enoxaparin (4 mg/kg); and aspirin (10 mg/kg) with clopidogrel (10
      mg/kg). RESULTS: Control period (pretreatment) CFRs were not significantly
      different between groups; average 7.0+/-0.3 CFRs/30 min (n=64). Tail bleeding
      time before drug(s) was 3.1+/-0.1 min (n=86). When administered alone, aspirin (4
      30 mg/kg), heparin (250 U/kg) or enoxaparin (4 mg/kg) had no effect on CFRs or
      bleeding time. Heparin (500 U/kg), enoxaparin (10 and 30 mg/kg) and clopidogrel
      (20 mg/kg) significantly decreased CFRs. Single administration of heparin (500
      U/kg) or enoxaparin (30 mg/kg) increased bleeding time by 4- or 11-fold. When co
      administered, aspirin 10 mg/kg and heparin 250 U/kg decreased CFRs, but also
      increased bleeding time by 11-fold. However, combination of aspirin and
      enoxaparin (4 mg/kg each), or aspirin and clopidogrel (10 mg/kg each), decreased
      CFRs with no effect on bleeding. CONCLUSIONS: In a preparation of arterial
      thrombosis in the rat, combinations of sub-efficacious (low) doses of aspirin
      with enoxaparin or clopidogrel inhibited thrombus formation without augmenting
      bleeding time. However, low-dose aspirin combined with heparin, whilst inhibiting
      thrombus formation, exacerbated bleeding time. If these findings translate into
      the clinic, the use of effective low-dose combinations may have therapeutic
      advantages.

PMID- 16410021
TI  - Epidemiological study on passive smoking among Japanese infants and smoking
      behavior of their respective parents: a nationwide cross-sectional survey.
AB  - BACKGROUND: Passive smoking is a well-known health hazard for infants. This study
      was conducted to: (1) estimate the prevalence of passive smoking among Japanese
      infants and (2) clarify the prevalence of indoor smoking and associating factors
      among parents having infants. METHODS: Subjects were all 53,575 infants born
      throughout Japan on January 10-17, 2001 or July 10-17, 2001. When the infants
      reached 6 months of age, the questionnaires were mailed to the homes. Family
      members answered questions that included information about the current smoking
      behavior of the parents. RESULTS: A total of 44,562 questionnaires (83.2%) were
      analyzed. The prevalence of smoking among the mothers and the fathers were 17.1%
      and 63.5%. The percentages of mothers and fathers who smoked indoors were 12.1%
      and 36.2%. The percentage of households where mothers and/or fathers smoked
      indoors was 37.5%. Multivariate logistic analysis indicated that young age,
      having a spouse who was a smoker, infants having many siblings, the mother not
      breast-feeding, and lower annual incomes had significantly higher odds ratios for
      both the mother's and the father's indoor smoking. CONCLUSIONS: Passive smoking
      is common among Japanese infants. To protect Japanese infants from passive
      smoking, further public health measures must be taken.

PMID- 16410022
TI  - Heparin incorporating liposomes as a delivery system of heparin from PET-covered
      metallic stents: effect on haemocompatibility.
AB  - We investigate the possibility of coating polymer-covered stents with heparin
      encapsulating liposomes for improving their haemocompatibility. Thin-film
      hydration (for multilamellar vesicles, MLV), and the dehydration-rehydration
      vesicle (DRV) methods are used for preparation of low-molecular weight heparin
      (LMWH)-encapsulating liposomes with varying lipid compositions. Liposomes are
      characterized for LMWH encapsulation and retention. For measurement of LMWH, a
      chromogenic technique is adjusted. For evaluation of heparin release from
      vesicles in platelet poor plasma (PPP) coagulation time is measured in presence
      of liposomal samples. Results reveal that LMWH encapsulation in liposomes is
      higher in DRV, however compositions with high encapsulation are leaky during
      buffer incubation. Most liposomes release LMWH slowly during plasma incubation
      (retention after 24 h ranges between 74% and 95%). Concerning the
      haemocompatibility of polyethylene terephthlate-covered stents after coating with
      LMWH-encapsulating liposomes, there is a marked increase (higher for DRV-coated
      stents compared to MLV) in plasma recalcification time compared to the control
      (plain blood) and reference (non-coated stent), which increases with blood
      material contact time. This is probably due to LMWH release, demonstrating that
      encapsulated LMWH retains its biological functionality. Interestingly, the DRV
      coated stents retained a high plasma recalcification time and a large number of
      liposomes on the stents (as proven by SEM studies) even after extensive washing
      (high shear conditions), proving that this method may be functional under high
      flow applying in vivo conditions.

PMID- 16410023
TI  - Zinc and copper: pharmacological probes and endogenous modulators of neuronal
      excitability.
AB  - As well as being key structural components of many proteins, increasing evidence
      suggests that zinc and copper ions function as signaling molecules in the nervous
      system and are released from the synaptic terminals of certain neurons. In this
      review, we consider the actions of these two ions on proteins that regulate
      neuronal excitability. In addition to the established actions of zinc, and to a
      lesser degree copper, on excitatory and inhibitory ligand-gated ion channels, we
      show that both ions have a number of actions on selected members of the voltage
      gated-like ion channel superfamily. For example, zinc is a much more effective
      blocker of one subtype of tetrodotoxin (TTX)-insensitive sodium (Na+) channel
      (NaV1.5) than other Na+ channels, whereas a certain T-type calcium (Ca2+) channel
      subunit (CaV3.2) is particularly sensitive to zinc. For potassium (K+) channels,
      zinc can have profound effects on the gating of certain KV channels whereas zinc
      and copper have distinct actions on closely related members of the 2 pore domain
      potassium channel (K2P) channel family. In addition to direct actions on these
      proteins, zinc is able to permeate a number of membrane proteins such as (S)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate
      receptors, Ca2+ channels and some transient receptor potential (trp) channels.
      There are a number of important physiological and pathophysiological consequences
      of these many actions of zinc and copper on membrane proteins, in terms of
      regulation of neuronal excitability and neurotoxicity. Furthermore, the
      concentration of free zinc and copper either in the synaptic cleft or neuronal
      cytoplasm may contribute to the etiology of certain disease states such as
      Alzheimer's disease (AD) and epilepsy.

PMID- 16410024
TI  - Lipid metabolism in cognitive decline and dementia.
AB  - This review will focus on the current knowledge on circulating serum and plasma
      risk factors of cognitive decline of degenerative (Alzheimer's disease, AD) or
      vascular origin (vascular dementia, VaD) linked to cholesterol homeostasis and
      lipoprotein disturbances, i.e. total cholesterol (TC), 24S-hydroxy-cholesterol,
      lipoprotein(a) (Lp(a)), or apolipoprotein E (APOE). These measures linked to
      lipoprotein metabolism appear to be altered in AD, VaD, or predementia syndrome
      relative to controls, but with contrasting results. At present, several studies
      have demonstrated the dependence of APOE serum levels upon the APOE genotype,
      nonetheless serum APOE levels seems not to be a credible risk factor or a
      biochemical marker for AD instead of APOE genotyping. In fact, there was no
      consistent association of serum or plasma apoE protein levels with the disease
      when controlled for APOE genotype. In addition, there are some evidence that
      higher Lp(a) levels could be linked with AD, although there are studies
      suggesting an increased presence of low molecular weight apo(a) in AD, VaD, and
      frontotemporal dementia, that are associated with elevated Lp(a) levels. In fact,
      the apo(a) gene is highly polymorphic in length due to variation in the numbers
      of a sequence encoding the apo(a) kringle 4 domain, and plasma levels of Lp(a)
      are inversely correlated with apo(a) size. Furthermore, although serum/plasma
      levels of TC and 24S-hydroxycholesterol are not credible diagnostic markers for
      AD and cognitive decline, the current evidence suggests that they may be
      modifiable risk/protective factors. The prevailing wisdom is that high TC is a
      risk factor for dementia. However, the relationship between TC and dementia may
      vary considerably depending on when cholesterol is measured over the life course
      or, alternatively, in relation to the underlying course of the disease. Several
      observational studies have suggested that statins, which are effective in
      lowering cholesterol, may reduce the risk of dementia, but the results of these
      reports are inconclusive. Thus, more studies with long-term follow-up and serial
      assessments of TC are needed to further clarify the causal relationship between
      cholesterol and dementia.

PMID- 16410025
TI  - Cytokine profiles in bipolar affective disorder: focus on acutely ill patients.
AB  - BACKGROUND: The role of the immune system in mood disorders is predominately
      supported by studies in unipolar major depression. However activation of the
      immune system has also been demonstrated in bipolar mania. Our study examines pro
      inflammatory and anti-inflammatory cytokines in both phases of bipolar affective
      disorder (BPAD). METHODS: Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha
      and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in
      patients with BPAD who were depressed, or manic and in healthy controls. RESULTS:
      Bipolar depression had significantly higher production of the pro-inflammatory
      cytokines, IL-8 (p < 0.001) and TNF-alpha (p < 0.05) compared to healthy
      subjects. The manic group also had increased production of IL-8 (p < 0.05) and
      TNF-alpha (p < 0.001) as compared to healthy subjects. Anti-inflammatory cytokine
      levels did not differ across the 3 groups. LIMITATIONS: A small sample size was
      studied. All patients remained on medication for this study. CONCLUSIONS: BPAD is
      associated with increased production of pro-inflammatory cytokines both in the
      manic and in the depressed phase as compared to healthy subjects. This is the
      first study, which examined both mania and bipolar depression.

PMID- 16410026
TI  - Late mitral annuloplasty failure: the loss of the ring.
AB  - An 81-year-old man complained with increasing dyspnoea and asthenia few months
      after a successful double mitral and tricuspid valvuloplasty intervention. The
      echocardiogram revealed a partial detachment of the mitral annuloplasty ring due
      to dehiscence determining a severe regurgitation. Curiously, at Color-Doppler
      analysis of mitral inflow, the prolapse of the detached ring produced a
      fascinating circular line inside the regurgitation signal, mimicking the shape of
      a gemstone ring. We described a case of a relatively uncommon cause of late
      mitral valvuloplasty failure characterized by a really unusual echocardiographic
      finding.

PMID- 16410027
TI  - Invasion assay of Listeria monocytogenes using Vero and Caco-2 cells.
AB  - The invasion ability of Listeria monocytogenes into cultured cells has been used
      to evaluate its pathogenicity. In this study, invasive ability was investigated
      using Vero and Caco-2 cell lines. The form of invasion showed no morphological
      differences between both cell lines inoculated with L. monocytogenes L89-H2 or
      L96-23C1 strains when double fluorescence stained with rhodamine and FITC or with
      Giemsa staining. Recovery count and recovery rate of L. monocytogenes from Vero
      cells was related to the number of inoculated bacteria (2 x 10(5) to 2 x
      10(7)/ml) in a bell-shape pattern, though the relationship was unclear in Caco-2
      cells. Recovery rate of L. monocytogenes was higher in Vero cells than Caco-2
      cells at a multiplicity of infection (MOI) 10, though the rates in both cells
      showed different stable stages over a considerably wide range of MOI. The
      recovery rate of all five L. monocytogenes strains from listeriosis patients was
      15% at MOI 10 from infected Vero cells, while meat-derived strains showed
      variable rates regardless of the serovar. These results suggest that the Vero
      cell line is suitable for an invasion assay and that a recovery rate of 15% may
      be the critical limit for the expression of pathogenicity in the host.

PMID- 16410028
TI  - Antimicrobial resistance among Campylobacter jejuni isolated from raw poultry
      meat at retail level in Denmark.
AB  - Campylobacter jejuni isolated from raw poultry meat collected at retail shops in
      Denmark in the period 1996-2003 were tested for susceptibility to seven
      antimicrobial agents. The food samples consisted of raw chicken meat and other
      raw poultry meat of domestic or imported origin. The highest levels of resistance
      among C. jejuni were observed for tetracycline, nalidixic acid and ciprofloxacin,
      whereas macrolide resistance was rarely detected. C. jejuni originating from
      other poultry meat (mainly duck and turkey meat) exhibited the highest
      occurrences of antimicrobial resistance monitored; approximately one third of the
      isolates were tetracycline resistant (N=100). Among chicken meat isolates, the
      occurrence of tetracycline resistance was significantly higher (P<0.005) in C.
      jejuni isolated from imported chicken meat (N=88) than in C. jejuni from Danish
      chicken meat (N=367). The same tendency was observed for chloramphenicol,
      nalidixic acid and ciprofloxacin (P<0.05). The trends in resistance in the period
      1996-2003 among C. jejuni isolates from chicken meat indicate a decrease in the
      occurrence of resistance towards fluoroquinolones. This may be due to reduced
      application of fluoroquinolones for food animals. Monitoring of the occurrence of
      antimicrobial resistance in C. jejuni isolated from raw uncooked poultry has been
      performed on a yearly basis since 1996, thus providing useful insight into
      consumer exposure to antimicrobial-resistant C. jejuni.

PMID- 16410029
TI  - Effect of particle size reduction on dissolution and oral absorption of a poorly
      water-soluble drug, cilostazol, in beagle dogs.
AB  - The purpose of the present study was to investigate the effects of particle size
      on the dissolution and oral absorption of cilostazol. Three types of suspensions
      having different particle size distributions were prepared of the hammer-milled,
      the jet-milled cilostazol crystals and the NanoCrystal spray-dried powder of
      cilostazol. In vitro dissolution rate of cilostazol was significantly increased
      by reducing the particle size. The dissolution curves of the cilostazol
      suspensions were in good agreement with the simulation based on the Noyes-Whitney
      equation. The bioavailability of cilostazol after oral administration to dogs was
      increased with reducing the particle size. While positive food effect on the
      absorption was observed for the suspensions made of the hammer-milled and the jet
      milled crystals, no significant food effect was found for the suspension made of
      the NanoCrystal cilostazol spray-dried powder. These results could be
      qualitatively predicted from the in vitro dissolution data using the bio-relevant
      media, FaSSIF and FeSSIF. In conclusion, the NanoCrystal technology is found to
      be efficient to improve the oral bioavailability of cilostazol and to avoid the
      food effect on the absorption.

PMID- 16410030
TI  - Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical efflux
      transporters in Caco-2 cell monolayers.
AB  - D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS 1000) is a widely
      used form of vitamin E. TPGS 1000 is comprised of a hydrophilic polar (water
      soluble) head and a lipophilic (water-insoluble) alkyl tail. TPGS 1000 has been
      used as a solubilizer, an emulsifier and as a vehicle for lipid-based drug
      delivery formulations. Most recently, TPGS 1000 has been recognized as an
      effective oral absorption enhancer. An enhancing effect is consistent with a
      surfactant-induced inhibition of P-glycoprotein (P-gp), and perhaps other drug
      transporter proteins; however, the exact inhibition mechanism(s) remain unclear.
      Therefore, in an attempt to generate additional knowledge, we have synthesized
      and tested various TPGS analogs containing different PEG chain length (TPGS
      200/238/400/600/1000/2000/3400/3500/4000/6000). These results demonstrate a
      relationship between TPGS PEG chain length and influence on rhodamine 123 (RHO)
      transport in Caco-2 monolayers, a relationship which may be illustrated using a
      Weibull distribution.

PMID- 16410031
TI  - Novel oral formulation safely improving intestinal absorption of poorly
      absorbable drugs: utilization of polyamines and bile acids.
AB  - In order to develop a novel oral formulation that can safely improve the
      intestinal absorption of poorly absorbable drugs, polyamines such as spermine
      (SPM) and spermidine (SPD) was examined as an absorption enhancing adjuvant in
      rats. The absorption of rebamipide, classified into BCS Class IV, from colon was
      significantly improved by SPM or SPD, and the enhancing ability of SPM was larger
      than that of SPD. As a possible mixing and/or interaction of polyamines with bile
      acids were expected, the combinatorial use of sodium taurocholate (STC) with
      polyamines was also examined. The absorption of rebamipide was drastically
      improved by the combinatorial use of SPM or SPD with STC. As STC itself did not
      enhance the absorption of rebamipide so much, it was considered that polyamines
      and STC had a synergistic enhancing effect. In-vivo oral absorption study was
      also performed to investigate the effectiveness and safety of polyamines and
      their combinatorial use with STC in rats. Although the enhancing effect slightly
      attenuated comparing with the in-situ loop study, the absorption of rebamipide
      was significantly improved and the combinatorial use of 10 mM SPM with 25 mM STC
      showed the largest enhancing effect. Histopathological studies clearly showed
      that any significant change in stomach and duodenum was not caused by SPM (10
      mM), SPD (10 mM) or their combinatorial use with STC (25 mM) at 1.5 or 8.0 h
      after oral administration. Taken all together, polyamines, especially SPM, and
      its combinatorial use with STC could improve the absorption of poorly absorbable
      drugs without any significant changes in gastrointestinal tract after oral
      administration in rats.

PMID- 16410032
TI  - Sugar malabsorption in functional abdominal bloating: a pilot study on the long
      term effect of dietary treatment.
AB  - BACKGROUND: Functional abdominal bloating is a functional bowel disorder
      dominated by a feeling of abdominal fullness without sufficient criteria for
      another functional gastrointestinal disorder. Gas-related complaints (i.e.,
      passage of flatus), which are present in a subgroup of these patients, might be
      associated with carbohydrate malabsorption. AIM: To evaluate the presence of
      lactose and/or fructose plus sorbitol malabsorption, and the long-term efficacy
      of malabsorbed sugar-free diets, in patients with Rome II criteria of functional
      abdominal bloating and gas-related symptoms. METHODS: Thirty-six consecutive
      patients (age, 51+/-3.1 years; sex, 12 M, 24 W) with Rome II criteria of
      functional abdominal bloating and gas-related symptoms were included in a pilot
      study. In all cases, the presence of malabsorption of both lactose (20 g) and
      fructose plus sorbitol (20+3.5 g) was assessed by means of hydrogen breath test.
      Patients with sugar malabsorption were put on a malabsorbed sugar-free diet.
      Follow-up visits were scheduled at both 1 and 12 months after starting the diet.
      Global rating scales of change as compared to the beginning of the study were
      used to assess symptom changes. RESULTS: Twenty-six of 36 patients (72.2%)
      presented sugar malabsorption (six lactose, 12 fructose plus sorbitol, and eight
      both). Seventeen of the 26 (65%) patients with malabsorption had symptoms of
      sugar intolerance during the 3-h breath testing period. All 26 were put on
      malabsorbed sugar-free diets. Eighty-one per cent of patients referred clinical
      improvement at 1-month visit, which was maintained at 12 months in 67% of them
      (complete improvement in 50% and partial improvement in 16.7%). CONCLUSIONS:
      Sugar malabsorption and intolerance seem to be frequent in patients with
      functional abdominal bloating and gas-related complaints. A malabsorbed sugar
      free diet might be a long-term effective therapy in a high percentage of
      patients. Further controlled clinical trials are warranted.

PMID- 16410033
TI  - Sitting on a chair or an exercise ball: various perspectives to guide decision
      making.
AB  - BACKGROUND: Prolonged sitting is recognized as a risk factor for the reporting of
      low back troubles. Despite the use of exercise balls in replacement of the office
      chair, little quantitative evidence exists to support this practice and hence
      motivated this research. Given the potential for several biological effects and
      mechanisms this study was approached with several layers of instrumentation to
      quantify differences in muscle activation, spine posture, spine compression and
      stability while sitting on an exercise ball versus a stable seat surface. Also,
      differences in the pressure distribution at the seat-user interface were
      quantified for the different seat surfaces to provide an objective perspective on
      the mechanism influencing perceived comfort levels. METHODS: Eight male subjects
      volunteered to sit for 30 min on an exercise ball and on a wooden stool. Muscle
      activity and spine position were used to model spine load and stability. An
      additional seven sat on an exercise ball and chair to examine pressure
      distribution over the contact area. FINDINGS: There was no difference in muscle
      activation profiles of each of the 14 muscles between sitting on the stool and
      ball. Calculated stability and compression values showed sitting on the ball made
      no difference in mean response values. The contact area of the seat-user
      interface was greatest on the exercise ball. INTERPRETATION: The results of this
      study suggest that prolonged sitting on a dynamic, unstable seat surface does not
      significantly affect the magnitudes of muscle activation, spine posture, spine
      loads or overall spine stability. Sitting on a ball appears to spread out the
      contact area possibly resulting in uncomfortable soft tissue compression perhaps
      explaining the reported discomfort.

PMID- 16410034
TI  - Current controversies in follicular lymphoma.
AB  - Follicular lymphoma (FL) is characterized by its responsiveness to initial
      therapy, a pattern of repeated relapses, and a tendency for histologic
      progression to a process resembling diffuse, large B-cell lymphoma. Treatment
      decisions are complicated by the many effective options now available including
      combinations of conventional chemotherapy and monoclonal antibody,
      radioimmunotherapy, new targeted agents, and autologous and allogeneic stem cell
      transplantation. For selected patients, "watch and wait" or involved field
      irradiation may still be the most appropriate strategy. When therapy is required,
      a combination of rituximab and conventional chemotherapy results in improved
      outcomes compared to chemotherapy alone. Radioimmunotherapy alone or in
      combination with chemotherapy is an attractive strategy for patients with
      relapsed disease and may prove to be appropriate first line therapy. The role of
      stem cell transplant in FL requires further investigation. Novel agents with
      varied mechanisms of action continue to be developed. Enrollment of patients into
      clinical trials designed to address the many unanswered questions in FL is
      essential to improving clinical outcomes.

PMID- 16410035
TI  - Brain blood flow changes measured by positron emission tomography during an
      auditory cognitive task in healthy volunteers and in schizophrenic patients.
AB  - OBJECTIVE: Cognitive deficit is an essential feature of schizophrenia. One of the
      generally used simple cognitive tasks to characterize specific cognitive
      dysfunctions is the auditory "oddball" paradigm. During this task, two different
      tones are presented with different repetition frequencies and the subject is
      asked to pay attention and to respond to the less frequent tone. The aim of the
      present study was to apply positron emission tomography (PET) to measure the
      regional brain blood flow changes induced by an auditory oddball task in healthy
      volunteers and in stable schizophrenic patients in order to detect activation
      differences between the two groups. METHOD: Eight healthy volunteers and 11
      schizophrenic patients were studied. The subjects carried out a specific auditory
      oddball task, while cerebral activation measured via the regional distribution of
      [15O]-butanol activity changes in the PET camera was recorded. RESULTS AND
      DISCUSSION: Task-related activation differed significantly across the patients
      and controls. The healthy volunteers displayed significant activation in the
      anterior cingulate area (Brodman Area - BA32), while in the schizophrenic
      patients the area was wider, including the mediofrontal regions (BA32 and BA10).
      The distance between the locations of maximal activation of the two populations
      were 33 mm and the cluster size was about twice as large in the patient group.
      CONCLUSIONS: The present results demonstrate that the perfusion changes induced
      in the schizophrenic patients by this cognitive task extends over a larger part
      of the mediofrontal cortex than in the healthy volunteers. The different pattern
      of activation observed during the auditory oddball task in the schizophrenic
      patients suggests that a larger cortical area - and consequently a larger variety
      of neuronal networks--is involved in the cognitive processes in these patients.
      The dispersion of stimulus processing during a cognitive task requiring sustained
      attention and stimulus discrimination may play an important role in the
      pathomechanism of the disorder.

PMID- 16410036
TI  - Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3:
      teratogenicity and reproductive toxicity studies in rats.
AB  - Green tea and its principal active ingredient, epigallocatechin gallate (EGCG),
      have been demonstrated to have anticancer properties through interactions with
      multiple biochemical processes. Since these processes are often crucial in normal
      fetal development it is important to evaluate the potential effects of EGCG on
      the fetus. EGCG preparations of >91% purity were administered to pregnant rats
      during organogenesis and development in order to define the safety of Teavigo, a
      high-concentration EGCG extract produced by the same novel method. In an initial
      preliminary study using subcutaneous and gavage routes, there was no evidence of
      any direct embryo-fetal toxicity, although some maternal toxicity was seen. In
      the main teratogenicity study, feeding pregnant rats diets supplemented at 1400,
      4200 or 14,000 ppm during organogenesis was non-toxic to dams or fetuses. A two
      generation study in rats fed 1200, 3600 or 12,000 ppm EGCG preparation showed no
      adverse effects on reproduction or fertility. The highest dose reduced the growth
      rate of offspring, and there was a slight increase in pup loss. A growth effect
      among pups was also seen at 3600 ppm, but in the second generation only. The
      lowest dose was considered the overall no-observed adverse effect level (NOAEL).
      As dams consumed twice the amount of feed during the crucial lactation period,
      the NOAEL was equivalent to 200 mg/kg/day EGCG preparation.

PMID- 16410037
TI  - Immunomodulation and antitumor activity of kappa-carrageenan oligosaccharides.
AB  - The modulation of carrageenan oligosaccharides from Kappaphycus striatum on the
      immune system in S180-bearing mice was investigated. The mice inoculated with
      S180 cell suspension were treated p.o. with carrageenan oligosaccharides (50, 100
      and 200 microg/g) for 14 days. The effects of carrageenan oligosaccharides on
      transplantable tumors and macrophage phagocytosis, quantitative hemolysis of
      sheep red blood cells (QHS), lymphocyte proliferation, the activity of natural
      killer cells (NK), production of interleukin-2 (IL-2) and tumor necrosis factor
      alpha (TNF-alpha) were studied. Carrageenan oligosaccharides could significantly
      inhibit the growth of transplantable sarcoma S180 and increase macrophage
      phagocytosis, the form of antibody secreted by spleen cells, spleen lymphocyte
      proliferation, NK cells activity, serumal IL-2 and TNF-alpha level in S180
      bearing mice. Considering all these results, it is suggested that carrageenan
      oligosaccharides exert their antitumor effect by promoting the immune system.

PMID- 16410039
TI  - Extracellular trehalose utilization by Saccharomyces cerevisiae.
AB  - Two haploid strains of Saccharomyces cerevisiae viz. MATalpha and MATa were grown
      in glucose and trehalose medium and growth patterns were compared. Both strains
      show similar growth, except for an extended lag phase in trehalose grown cells.
      In both trehalose grown strains increase in activities of both extracellular
      trehalase activities and simultaneous decrease in extracellular trehalose level
      was seen. This coincided with a sharp increase in extracellular glucose level and
      beginning of log phase of growth. Alcohol production was also observed. Secreted
      trehalase activity was detected, in addition to periplasmic activity. It appeared
      that extracellular trehalose was hydrolyzed into glucose by extracellular
      trehalase activity. This glucose was utilized by the cells for growth. The
      alcohol formation was due to the fermentation of glucose. Addition of
      extracellular trehalase caused reduction in the lag phase when grown in trehalose
      medium, supporting our hypothesis of extracellular utilization of trehalose.

PMID- 16410038
TI  - Reversal of drug resistance in P-glycoprotein-expressing T-cell acute
      lymphoblastic CEM leukemia cells by copper N-(2-hydroxy acetophenone) glycinate
      and oxalyl bis (N-phenyl) hydroxamic acid.
AB  - Multiple drug resistance (MDR) represents a major obstacle to successful
      application of chemotherapy and a basic problem in cancer biology. MDR occurs at
      the cellular level and is multi-factorial in nature. The multidrug resistance
      gene, MDR1, and its gene product P-glycoprotein (P-gp) are now well known as an
      important determinant of MDR. Much effort has been devoted to develop P-gp
      inhibitors to modulate resistance. However, most of these resistance-modifying
      agents (RMA) are too toxic at the required doses. Therefore, the development of
      novel RMAs to overcome MDR represents a major challenge to modern cancer
      chemotherapy. In the present investigation, we describe the effect of oxalyl bis
      (N-phenyl) hydroxamic acid (OBPHA) and copper N-(2-hydroxy acetophenone)
      glycinate (CuNG) on multidrug-resistant P-gp-expressing CEM/ADR5000 T-cell acute
      lymphoblastic leukemia cells. CuNG, a known depleting agent for glutathione (GSH)
      and inhibitor of glutathione S-transferase (GST) and multidrug resistance-related
      protein 1 (MRP1), also inhibited P-gp-mediated doxorubicin accumulation and
      retention. The resistance-modifying effects of OBPHA were stronger than that of
      CuNG. Both novel RMAs overcame drug resistance more efficiently than verapamil, a
      well-known P-gp inhibitor. OBPHA and CuNG exposure resulted in an increased
      doxorubicin accumulation after 1-3h incubation by down-regulation of P-gp
      expression after 24h incubation. This is a clue that different mechanisms may
      contribute to modulation of P-gp-mediated drug resistance by these compounds.

PMID- 16410040
TI  - Calcium transport and signaling in the mammary gland: targets for breast cancer.
AB  - The mammary gland is subjected to extensive calcium loads during lactation to
      support the requirements of milk calcium enrichment. Despite the indispensable
      nature of calcium homeostasis and signaling in regulating numerous biological
      functions, the mechanisms by which systemic calcium is transported into milk by
      the mammary gland are far from completely understood. Furthermore, the
      implications of calcium signaling in terms of regulating proliferation,
      differentiation and apoptosis in the breast are currently uncertain. Deregulation
      of calcium homeostasis and signaling is associated with mammary gland
      pathophysiology and as such, calcium transporters, channels and binding proteins
      represent potential drug targets for the treatment of breast cancer.

PMID- 16410041
TI  - The malaria parasite Plasmodium falciparum histones: organization, expression,
      and acetylation.
AB  - Histones are the building units of nucleosomes and play essential roles in DNA
      replication, repair and transcription. A comprehensive analysis of histone genes
      revealed that the Plasmodium falciparum genome encodes a canonical form of each
      core histone and four histone variants H2A.Z, H3.3, centromere-specific H3
      (CenH3), and H2Bv. Mass spectrometry confirmed the synthesis of all histones
      except CenH3. Real-time reverse transcriptase-polymerase chain reaction and
      immunoblotting detected a dramatic increase in core histone gene expression
      during the late trophozoite stages, consistent with their role in replication
      related nucleosome assembly. In contrast, the expression of variant histones
      decreased in mid- or late trophozoite stages. The N-terminal tails of histones
      participate in transcription regulation through covalent modifications,
      especially at the lysine residues. In accordance, mass spectrometry analysis
      revealed acetylation of lysines and methylation of lysines and arginines in the N
      termini of H3, H3.3, and H4. Moreover, we identified a new pattern of lysine
      modifications of the H2A.Z variant. Using a panel of acetylation-specific
      antibodies, we found that K5, K8, and K12 of H4 were abundantly acetylated at a
      relatively steady level throughout the erythrocytic cycle. In comparison, the H3
      K9 acetylation increased in late trophozoite and schizont stages, while H4-K16
      acetylation peaked in mid-trophozoite stage. We have also shown that despite the
      sequence divergence in the PfH3 N-terminus from their mammalian homologues, the
      recombinant PfH3 was still efficiently acetylated by both recombinant and native
      PfGCN5 at K9 and K14. This study suggests that histone replacement and the
      dynamic histone modifications play important roles in regulating gene expression
      during erythrocytic development of the malaria parasite.

PMID- 16410042
TI  - 'Facilitated tucking by parents' in pain management of preterm infants-a
      randomized crossover trial.
AB  - BACKGROUND: There is a need for a safe and effective non-pharmacological pain
      management method for preterm infants. The parents could be given an active role
      in the pain management which may help the parents to cope with the stress related
      to painful situations of the infant. AIMS: To examine the effectiveness of a
      method called 'facilitated tucking by parents' (a parent holds the infant in a
      flexed position) in pain management during endotracheal/pharyngeal suctioning of
      preterm infants. In addition, the parental perception of the method was studied.
      STUDY DESIGN: A randomized crossover trial. SUBJECTS: Twenty preterm infants with
      one of their parents participated in the study. Infants' gestational age ranged
      from 24 to 33 (median 28) weeks and postnatal age from 6 to 37 days (median 15
      days). OUTCOME MEASURES: The primary outcome was the Neonatal Infant Pain Scale
      (NIPS) score. Heart rate and oxygen saturation were recorded. Parents completed a
      questionnaire about their perception of the procedure. RESULTS: The highest NIPS
      score was median 3 (range from 2 to 6) using 'facilitated tucking by parents' and
      median 5 (range from 2 to 7) without tucking during suctioning (p < 0.001). The
      infants calmed down more quickly after 'facilitated tucking by parents' (5 s vs.
      17 s, p = 0.024). Nineteen out of twenty parents preferred facilitated tucking
      during suctioning compared to control care. CONCLUSIONS: Facilitated tucking by
      parents is an effective and safe pain management method during suctioning of
      preterm infants. This study shows that parents can be given an active role in the
      pain care of their preterm infants.

PMID- 16410043
TI  - Tepidimonas thermarum sp. nov., a new slightly thermophilic betaproteobacterium
      isolated from the Elisenquelle in Aachen and emended description of the genus
      Tepidimonas.
AB  - Several non-pigmented bacterial isolates, with an optimum growth temperature of
      about 50-55 degrees C, were recovered from the Elisenquelle at Aachen, Germany.
      Phylogenetic analysis of the 16S rRNA gene sequence of strains AA-1(T) and AA-2
      indicated that these organisms represent a new species of the genus Tepidimonas.
      The major fatty acids of strains AA-1(T) and AA-2 are 16:0 and 16:1 omega7c.
      Ubiquinone 8 is the major respiratory quinone, the major polar lipids are
      phosphotidylethanolamine and phosphotidylglycerol. The new isolates are aerobic;
      thiosulfate is oxidized to sulfate in the presence of a metabolizable carbon
      source. The organism assimilated organic acids and amino acids, but did not
      assimilate carbohydrates or polyols. On the basis of the phylogenetic analyses,
      physiological and biochemical characteristics, we propose that strains AA-1(T)
      (=LMG 23094(T); =CIP 108777(T)) and AA-2 (=LMG 23095; =CIP 108778) represents a
      new species for which we recommend the name Tepidimonas thermarum.

PMID- 16410044
TI  - Isolation and identification of Gluconacetobacter azotocaptans from corn
      rhizosphere.
AB  - Six acetic acid producing, diazotrophic bacteria were isolated from soil adhering
      to corn roots. These isolates were shown to be Gluconacetobacter azotocaptans and
      they shared some features with G. johannae and G. diazotrophicus but differed on
      the basis of colony morphology on different media, use of carbon sources and use
      of l-amino acids as a nitrogen source. The species identity was confirmed using
      16S rDNA sequence analysis, PCR amplification of 16S rRNA gene with species
      specific primers and amplified rDNA restriction analysis. This is the first
      report of the presence of this bacteria on corn plants. Scope of the paper: This
      is the first report of the occurrence and association of Gluconacetobacter
      azotocaptans with corn.

PMID- 16410045
TI  - A new type of anti-ganglioside antibodies present in neurological patients.
AB  - High titers of anti-GA1 antibodies have been associated with neurological
      syndromes. In most cases, these antibodies cross-react with the structurally
      related glycolipids GM1 and GD1b, although specific anti-GA1 antibodies have also
      been reported. The role of specific anti-GA1 antibodies is uncertain since the
      presence of GA1 in the human nervous system has not been clarified. A rabbit was
      immunized with GD1a and its sera were screened for antibody reactivity by
      standard immunoassay methods (HPTLC-immunostaining and ELISA). Anti-GD1a
      antibodies were not detected but, unexpectedly, anti-GA1 IgG-antibodies were
      found. Antibody binding to GA1 was inhibited by soluble GA1 but also by GD1a.
      These results indicate that the rabbit produced antibodies that recognize
      epitopes present on the glycolipids, that are absent or not exposed on solid
      phase adsorbed GD1a. We investigated the presence of these unusual anti
      ganglioside antibodies in normal and neurological patient sera. Approximately,
      10% of normal human sera contained low titer of specific anti-GA1 IgG-antibodies
      but none of them recognized soluble GD1a. High titers of IgG-antibodies reacting
      only with GA1 were detected in 12 patient sera out of 325 analyzed. Of these, 6
      sera showed binding that was inhibited by soluble GD1a and four of them also by
      GM1. This new type of anti-ganglioside antibodies should be considered important
      elements for understanding of the pathogenesis of these diseases as well as their
      diagnosis.

PMID- 16410046
TI  - Ensemble of single quadrupolar nuclei in rotating solids: sidebands in NMR
      spectrum.
AB  - A novel way is proposed to describe the evolution of nuclear magnetic
      polarization and the induced NMR spectrum. In this method, the effect of a high
      intensity external static magnetic field and the effects of proper Hamiltonian
      left over interaction components, which commute with the first, are taken into
      account simultaneously and equivalently. The method suits any concrete NMR
      problem. This brings forth the really existing details in the registered spectra,
      evoked by Hamiltonian secular terms, which may be otherwise smoothed due to
      approximate treatment of the effects of the secular terms. Complete analytical
      expressions are obtained describing the NMR spectra including the rotational
      sideband sets of single quadrupolar nuclei in rotating solids.

PMID- 16410047
TI  - Primary open-angle glaucoma patients have reduced levels of blood docosahexaenoic
      and eicosapentaenoic acids.
AB  - The aetiology of primary open-angle glaucoma (POAG), which is the commonest cause
      of non-remediable blindness and visual impairment, is not well understood.
      Nevertheless, increased intraocular pressure, and vascular factors such as ocular
      blood flow deficits are thought to be risk factors. There is evidence of
      decreased optic nerve blood velocity and increased red blood cell aggregability
      in POAG. These factors are influenced by fatty acids. We have investigated if
      glaucoma patients have abnormal blood fatty acid composition. Patients with POAG
      (n=10) and their healthy siblings (n=8) were enrolled. Compared with their
      healthy siblings, the glaucoma patients had reduced eicosapentaenoic (EPA,
      P<0.01), and docosahexaenoic (DHA, P<0.05) fatty acids and total omega3 long
      chain polyunsaturated fatty acids (LCPUFA) (P<0.05) in red cell choline
      phosphoglycerides (CPG); decreased EPA (P<0.05) in ethanolamine phosphoglycerides
      (EPG); lower EPA (P<0.05) and total omega3 LCPUFA (P<0.05) in serine
      phosphoglycerides (SPG). Similarly, they had reduced EPA, DHA and total omega3
      LCPUFA in plasma CPG (P<0.005) and triglycerides (P<0.05). These findings may be
      significant, since EPA and DHA could modulate impaired systemic microcirculation
      and ocular blood flow and optic neuropathy, which are the main physiological
      changes associated with glaucoma.

PMID- 16410048
TI  - Plant sterols combined with exercise for the treatment of hypercholesterolemia:
      overview of independent and synergistic mechanisms of action.
AB  - At present, dyslipidemia is most commonly treated with lipid-altering
      pharmacological therapies. However, safety concerns regarding the use of these
      agents have prompted the need for safe and efficacious nonpharmacological lipid
      altering interventions. One such natural therapy is the combination of plant
      sterols and endurance training. This combination lifestyle intervention has been
      shown to decrease total cholesterol, low-density lipoprotein (LDL) cholesterol
      and triglyceride concentrations while increasing high-density lipoprotein (HDL)
      cholesterol concentrations. However, the mechanisms that underlie these positive
      lipid alterations have yet to be clarified. Thus, the purpose of this review is
      to evaluate individual effects of plant sterols and exercise training on lipid
      levels while attempting to elucidate the possible independent and synergistic
      mechanisms of action responsible for these modulations. Results reveal that plant
      sterols decrease both total and LDL cholesterol levels by reducing exogenous
      cholesterol absorption by way of cholesterol displacement in the intestinal
      lumen. Additionally, the intestinal membrane transport proteins, ABCG5, ABCG8, as
      well as NPC1L1, have also been implicated in plant sterol-mediated cholesterol
      lowering. Conversely, exercise decreases triglyceride levels by reducing hepatic
      very low-density lipoprotein secretion and increasing skeletal lipoprotein lipase
      activity. In addition, endurance training was shown to increase HDL cholesterol
      levels by way of HDL subfraction alterations, in conjunction with changing
      reverse cholesterol transport enzyme activities. Moreover, plant sterols and
      exercise may work synergistically to alter lipid levels by modulating lipoprotein
      transport, composition, release and metabolism. In sum, the present review lends
      further insight as to the metabolic benefits of adopting a healthy lifestyle,
      including plant sterols and endurance training, in the treatment of dyslipidemia.

PMID- 16410049
TI  - Childhood leukaemias and CNS tumours: correlation of international incidence
      rates.
AB  - Childhood leukaemia has a potential infectious aetiology whilst infections may
      also be linked to paediatric central nervous system (CNS) tumours. Using data
      from 29 countries we investigated the correlation between international incidence
      rates of childhood leukaemia and CNS tumours, focusing on acute lymphoblastic
      leukaemia (ALL), astrocytoma and ependymoma-subtypes that are hypothesised to
      have an infectious aetiology. Relationships between incidence rates and national
      demographic factors were also examined using Pearson's correlation coefficient to
      quantify associations. Comparing two diagnostic categories of leukaemia with four
      groups of CNS tumours, a highly significant positive correlation was found
      between ALL and astrocytoma (r = 0.57, P = 0.002). Higher rates of ALL and CNS
      tumours were associated with increased affluence, with the strongest correlation
      for Gross Domestic Product per capita and CNS tumours (r = 0.70, P < 0.001).
      National incidence rates of childhood ALL and astrocytomas were highly correlated
      and this may reflect a common environmental cause whose origin may be infectious
      in nature. International incidence of ALL and CNS tumours were also correlated
      with economic related factors. Variation in levels of ascertainment may partially
      explain this, although childhood environmental exposures related to infections
      will also be affected by levels of affluence.

PMID- 16410050
TI  - Extraction and characterisation of gelatine from Atlantic salmon (Salmo salar)
      skin.
AB  - Gelatine was extracted from Atlantic salmon and Atlantic cod skin by the acid
      extraction process. After filtration and ion exchange treatment the extracts were
      colourless and free from fishy odour. In three separate experiments the average
      yields of gelatine from salmon and cod skins were 39.7% (+/-2.2%) and 44.8% (+/
      0.2%) respectively, on a dry matter basis. Gelatine from salmon contained
      slightly more hydroxyproline and proline (16.6%) than cod gelatine (15.4%),
      whereas the content of serine was lower (4.6% versus 6.3%). Salmon gelatine
      expressed slightly higher gelling temperature (12 degrees C) than cod gelatine
      (10 degrees C), and higher initial gel strength. During storage at 10 degrees C,
      gel strengths were increased and more so with gels made from cod than from salmon
      gelatine. Hence, gels made from cod and salmon gelatines extracted at 56 degrees
      C achieved the same gel strength (195g) after 7days of storage. Gelatines
      extracted at a higher temperature (65 degrees C) gave lower gel strengths.

PMID- 16410051
TI  - The H2 MAPT haplotype is associated with familial frontotemporal dementia.
AB  - There is now considerable evidence that the gene encoding for tau protein (MAPT)
      is implicated in frontotemporal dementia (FTD). The role of MAPT haplotypes in
      neurodegenerative diseases has been suggested, but their contribution in familial
      dementia has not been extensively investigated. Here, we investigated (1) the
      association between the MAPT haplotypes and sporadic (sFTD) or familial FTD
      (FFTD) (controls n = 99, sFTD n = 53, FFTD n = 50), (2) the interactive effect
      between MAPT haplotypes and APOE gene. We found an overrepresentation of H2
      haplotype (OR = 1.83, P = 0.029) and of H2H2 genotype in FFTD patients (OR =
      6.09, P = 0.007). This association was even stronger in APOE e4 negatives FFTD
      (H2: OR = 2.9, P = 0.001; H2H2: OR = 12.67, P = 0.001). Our results support idea
      that the MAPT H2 haplotype is a risk factor for FFTD. This locus could contain
      this or other inheritable genetic determinants contributing to increase risk of
      developing dementia.

PMID- 16410052
TI  - Generality and specificity in cognitive aging: a volumetric brain analysis.
AB  - OBJECTIVE: To investigate whether, in old age, brain volume differences are
      associated with age-related change in general mental ability and/or specific
      cognitive abilities. METHODS: The authors investigate the association between
      brain volumes and current cognitive function in a well-characterized sample of
      healthy old people (aged 79-80) whose intelligence was recorded at age 11. This
      allowed estimation of intellectual change over the life span. RESULTS: After
      accounting for childhood intelligence, associations were found between specific
      cognitive measures and brain volumes. An association was also found between
      volumes and the general intelligence factor g. After removing the influence of g
      from each of the specific cognitive measures, no remaining significant
      associations were found between brain volumes and the specific part of each test.
      CONCLUSIONS: Generalized cognitive aging is associated with brain volume
      differences, but there is no evidence in this sample that specific components of
      cognitive aging are associated with differences in brain volume.

PMID- 16410053
TI  - In hepatocytes the regulation of NOS-2 activity at physiological L-arginine
      levels suggests a close link to the urea cycle.
AB  - High-output synthesis of nitric oxide (NO) by the inducible isoform of NO
      synthases (NOS-2) plays an important role in hepatic pathophysiological processes
      and may contribute to both organ protection and organ destruction during
      inflammatory reactions. As they compete for the same substrate, L-arginine, an
      interdependence of NOS-2 and arginase-1 has been repeatedly observed in cells
      where arginase-1 is cytokine-inducible. However, in hepatocytes, arginases are
      constitutively expressed and thus, their impact on hepatic NOS-2-derived NO
      synthesis as well as the influence of L-arginine influx via cationic amino acid
      transporters during inflammatory reactions are still under debate. Freshly
      isolated rat hepatocytes were cultured for 24h in the presence of various L
      arginine concentrations with or without cytokine addition and nitrite and urea
      accumulation in culture supernatants was measured. We find that both, cytokine
      induced NOS-2 and arginase activities strongly depend on extracellular L-arginine
      concentrations. When we competed for L-arginine influx via the cationic amino
      acid transporters by addition of L-lysine, we find a 60-70% inhibition of
      arginase activity without significant loss of NOS-2 activity. Addition of L
      valine, as an arginase inhibitor, leads to a 25% increase in NO formation and an
      80-90% decrease in arginase activity. Interestingly, product inhibition of
      arginase and competitive inhibition of CATs through the addition of L-ornithine
      leads to a highly significant increase in hepatocytic NOS-2 activity with a
      concomitant and complete abolishment of its dependence on extracellular L
      arginine concentrations. In conclusion, hepatocytic NOS-2 activity shows a
      surprising pattern of dependence on exogenous L-arginine concentrations.
      Inhibition and competition experiments suggest a relatively tight link of NOS-2
      and urea cycle activities. These data stress the hypothesis of a metabolon-like
      organization of the urea cycle together with NOS-2 in hepatocytes as excess L
      ornithine will be metabolized to l-arginine and thereby increases NO production.

PMID- 16410054
TI  - Mutation and biochemical analysis of patients belonging to the cblB
      complementation class of vitamin B12-dependent methylmalonic aciduria.
AB  - Methylmalonic aciduria, cblB type (OMIM 251110) is an inborn error of vitamin
      B(12) metabolism that occurs due to mutations in the MMAB gene. MMAB encodes the
      enzyme ATP:cobalamin adenosyltransferase, which catalyzes the synthesis of the
      coenzyme adenosylcobalamin required for the activity of the mitochondrial enzyme
      methylmalonyl CoA mutase (MCM). MCM catalyzes the isomerization of methylmalonyl
      CoA to succinyl CoA. Deficient MCM activity results in methylmalonic aciduria and
      a susceptibility to life-threatening acidotic crises. The MMAB gene was sequenced
      from genomic DNA from a panel of 35 cblB patients, including five patients
      previously investigated. Nineteen MMAB mutations were identified, including 13
      previously unknown mutations. These included 11 missense mutations, two
      duplications, one deletion, four splice-site mutations, and one nonsense
      mutation. None of these mutations was identified in 100 control alleles. Most of
      the missense mutations (9/11) were clustered in exon 7; many of these affected
      amino acid residues that are part of the probable active site of the enzyme. One
      previously described mutation, c.556C >T (p.R186W), was particularly common,
      accounting for 33% of pathogenic alleles. It was seen almost exclusively in
      patients of European background and was typically associated with presentation in
      the first year of life.

PMID- 16410055
TI  - Temporal variation of airborne fungi concentrations and related factors in subway
      stations in Seoul, Korea.
AB  - This study was performed to assess the levels of fungi concentration in subway
      stations in Seoul, Korea, and to investigate factors contributing to these
      concentrations. Ninety air samples were collected hourly over the course of a day
      from five different subway stations. In addition, five settled dust samples and
      12 stagnant water samples were collected to investigate these as potential
      sources of fungi contamination. The number of passengers and frequency of passing
      trains were also determined during the sampling periods, as they were considered
      potential factors influencing the airborne fungi concentrations at a given time
      during the day. The airborne fungi concentrations, as a function of time, were
      log-normally distributed. The airborne fungi concentrations measured during the
      morning and evening commute hours (during which the number of passengers and
      frequency of passing trains was highest) were significantly higher than those
      measured during non-commute hours. High concentrations of fungi were found in the
      settled dust samples, suggesting that the settled dust may have been the main
      source of airborne fungi concentration. The air movement generated mainly by
      passengers and additionally by trains might have played a role in suspending the
      fungi from the settled dust. It was also found that stagnant water might be a
      potential source of airborne fungi.

PMID- 16410056
TI  - Support versus corroboration.
AB  - Numerous metrics have been developed that attempt to assess the reliability of
      phylogenetic trees. Several of these commonly used measures of tree and tree
      branch support are described and discussed in the context of their relationship
      to Popperian corroboration. Claims that measures of support indicate the accuracy
      of phylogenetic trees or provide information for tree choice are rebutted.
      Measures of support are viewed as being of heuristic value within a given
      phylogenetic framework for describing the precision of the data based on
      perturbations to the data. However, no direct link is observed between the
      calculation of measures of support and corroboration. Direct measures of support,
      but not re-sampling or randomization methods, may play a more specific role in
      phylogenetic inference by providing the tools to search for falsifiers that could
      be the subject of future rounds of hypothesis testing.

PMID- 16410057
TI  - Swelling and vacuolisation of mitochondria in transgenic SOD1-ALS mice: a
      consequence of supranormal SOD1 expression?

PMID- 16410058
TI  - High pressure-induced changes in bovine milk proteins: a review.
AB  - High pressure (HP)-induced changes in the proteins of bovine milk have become an
      area of considerable research interest in recent years; as a result, there is now
      a detailed understanding of the effects of HP on casein micelles and whey
      proteins. HP treatment at pressures >400 or >100 MPa denatures the two most
      abundant whey proteins, alpha-lactalbumin (alpha-la) and beta-lactoglobulin (beta
      lg), respectively. The majority of denatured beta-lg in HP-treated milk
      associates with the casein micelles, although some denatured beta-lg remains in
      the serum phase or is attached to the milk fat globule membrane; HP-denatured
      alpha-la is also associated with the milk fat globules. Casein micelles are
      disrupted on treatment at pressures >200 MPa; the rate and extent of micellar
      disruption increases with pressure and is probably due to the increased
      solubility of calcium phosphate with increasing pressure. On prolonged treatment
      at 250-300 MPa, reassociation of micellar fragments occurs through hydrophobic
      bonding; this process does not occur at a pressure >300 MPa, leading to
      considerably smaller micelles in such milk. As a result of HP-induced changes,
      the size, number, hydration, composition and light-scattering properties of
      casein micelles in HP-treated milk differ considerably from those in untreated
      milk.

PMID- 16410059
TI  - Dens evaginatus: literature review, pathophysiology, and comprehensive treatment
      regimen.
AB  - Dens evaginatus (DE) is an uncommon dental anomaly, having been well documented
      since 1925. It occurs primarily in people of Asian descent and is exhibited by
      protrusion of a tubercle from occlusal surfaces of posterior teeth, and lingual
      surfaces of anterior teeth. Tubercles have an enamel layer covering a dentin core
      containing a thin extension of pulp. These cusp-like protrusions are susceptible
      to pulp exposure from wear or fracture because of malocclusion, leading to pulpal
      complications soon after eruption. Endodontic intervention of permanent teeth
      with immature roots is unpredic for inflamed pulps, and leaves a tooth with
      compromised root structure when treating necrotic pulps. Efforts to ensure root
      maturity have involved preventive or prophylactic treatment with varying degrees
      of pulp invasiveness. Treatment options have changed as technology and materials
      have improved. The goal is to review the literature and pathophysiology regarding
      DE, and present a new comprehensive treatment regimen, including a truly
      prophylactic approach without pulpal invasiveness. A case study of a mestizo with
      DE is documented. Treatment of four affected mandibular premolars exhibiting
      three distinct diagnostic categories will illustrate various aspects of the
      treatment protocol presented, and tooth morphology of the anomaly is shown to aid
      clinical recognition.

PMID- 16410060
TI  - Anatomical study of C-shaped canals in mandibular second molars by analysis of
      computed tomography.
AB  - The aim of this study was to investigate the prevalence and configuration of the
      C-shaped canal using serial axial computed tomography images of the mandibular
      second molars that had not been restored severely or treated endodontically, and
      to compare the thickness of the remaining tooth structure from the center of the
      canal to the outer surface of the deepest groove area in C-shaped mandibular
      second molar to that of "danger zone of perforation" in normal mandibular second
      molar. This distance was measured at the cervical, middle, and apical third level
      each. From 220 teeth, C-shaped canals were found in 98 teeth (44.5%). Almost all
      the grooves were directed lingual (99%). The continuous C-shaped canal was the
      most frequently found (49%) and the separated canal was the least (17.4%). The
      thinnest remaining tooth structure in the groove area of the C-shaped mandibular
      second molar was not different from that of the danger zone of normal mandibular
      second molar at the three levels (p > 0.05).

PMID- 16410061
TI  - Incidence of instrument separation using LightSpeed rotary instruments.
AB  - The use of nickel-titanium rotary instrument systems has gained popularity over
      the past 10 years. One of these instrument systems is the LightSpeed (LightSpeed
      Technology, Inc, San Antonio, TX). One drawback for all nickel-titanium rotary
      instruments is the incidence of instrument separation. The purpose of this study
      was to evaluate the incidence of nonretrievable instrument separation using the
      LightSpeed system in a clinical setting. A total of 3543 canals were treated over
      a 24 month period and during that time, 46 LightSpeed instruments were separated
      and found to be nonretrievable, resulting in a separation rate of 1.30%. This
      rate was lower than previous reported studies.

PMID- 16410062
TI  - Identification of cultivable microorganisms from root canals with apical
      periodontitis following two-visit endodontic treatment with antibiotics/steroid
      or calcium hydroxide dressings.
AB  - The study was aimed at comparing the efficacy of disinfection of root canals with
      periapical radiolucencies when treated with either antibiotics/steroid
      medicaments (Ledermix or Septomixine) or a calcium hydroxide paste (Calasept).
      Microbiological samples were taken before and after two-visit endodontic
      treatment from 88 canals with apical periodontitis. All of the canals but one (87
      of 88) had cultivable growth before treatment. After dressing with Ledermix,
      Septomixine, or Calasept, the percentages of canals remained with positive growth
      were 48% (13 of 27), 31% (8 of 26), and 31% (11 of 35), respectively. The chi(2)
      tests showed there were no significant differences in the number of canals with
      positive growth or mean colony forming units counts after instrumentation,
      irrigation and dressing. In the Ledermix group, 38 strains of bacteria were
      recovered. The Septomixine group had 25 strains, and the Calasept group had 25
      strains. Gram-positive facultative anaerobic cocci (including staphylococci and
      streptococci) were more prevalent than the Gram-negative obligate anaerobic rods
      after treatment in all three groups. Similarities in the reduced number of canals
      with residual growth, and the prevalence of Gram-positive facultative anaerobic
      cocci suggest that the use of different inter-appointment dressings produced
      similar microbiological outcomes. However, factors other than the antimicrobial
      effectiveness of intracanal medicaments may also be responsible for the results
      observed.

PMID- 16410063
TI  - Role of IL-2 and helper T-lymphocytes in limiting periapical pathosis.
AB  - The purpose of this study was to examine the role of IL-2 and helper T
      lymphocytes in the development of periradicular lesions in rats. In control
      animals, periradicular lesions developed within 28 days following pulpal
      infection. Immunologically, some anti IL-2 and anti CD4-reactive helper T
      lymphocytes infiltrated the periapical tissue at 14 days, and their numbers
      increased at 28 days. In experimental animals, tacrolimus (FK506) was injected
      every day to inhibit the IL-2 production by helper T-cells. Histologically, the
      pulpal necrosis and periradicular inflammation in tacrolimus-treated rats were
      more severe than those in the control rats. Furthermore, the areas of pulpal
      necrosis and periradicular lesion in the immunosuppressed rat were significantly
      greater than those in the normal ones. The numbers of IL-2- and CD4-positive
      cells in the lesion of the experimental rats were statistically lower than those
      of the control ones. These results show that the decrease in IL-2 might have
      promoted the development of periradicular lesions.

PMID- 16410064
TI  - Examination of the signal transduction pathways leading to upregulation of tissue
      type plasminogen activator by interleukin-1alpha in human pulp cells.
AB  - Tissue type plasminigen activator (t-PA) is one of the important proteolysis
      factors in the pathogenesis of pulpal inflammation. However, the mechanisms and
      signal transduction pathways involved in the production of t-PA in human pulp
      cells are not fully understood. The purpose of this study was to investigate the
      t-PA activity in human pulp cells stimulated with various pharmacological agents.
      IL-1alpha was used to evaluate t-PA activity in human pulp cells using casein
      zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search
      possible signal transduction pathways, p38 inhibitor SB203580, MEK inhibitor
      U0126, and phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002 were added to
      test how they modulated the t-PA activity. The main casein secreted by human pulp
      cells migrated at 70 kDa and represented t-PA. Secretion of t-PA was found to be
      stimulated with IL-1alpha during 2 day cultured period (p < 0.05). From the
      results of casein zymography and ELISA, SB203580, U0126, and LY294002
      significantly reduced the IL-1alpha-stimulated t-PA production, respectively (p <
      0.05). Our findings demonstrated that IL-1alpha enhance t-PA production in human
      pulp cells, and the signal transduction pathways p38, MEK, and PI3K are involved
      in the inhibition of t-PA. SB203580, U0126, and LY294002 suppress t-PA activity
      and may also have important implication for pharmacological intervention.

PMID- 16410065
TI  - Histological study of periradicular tissue responses to uninfected and infected
      devitalized pulps in dogs.
AB  - Uninfected necrotic tissue, such as that which follows a myocardial or cerebral
      infarct, is capable of inducing an inflammatory reaction. Eventually, the infarct
      is organized by granulation tissue. Why then, does uninfected devitalized pulp
      tissue, such as in traumatized teeth, not cause periradicular inflammation and
      does not become organized by granulation tissue? Four beagle dogs were used in
      this experiment. A total of 48 teeth, which included 24 maxillary and 24
      mandibular incisors, were aseptically devitalized, leaving residual pulp tissues
      in the root canals, and equally divided into two groups. Group A (24 uninfected):
      A sterile cotton pellet was placed deep into the canal orifice before the pulp
      chamber and access opening were closed with a layer of zinc-oxide eugenol cement
      followed by glass ionomer cement. Group B (24 infected): The teeth were left open
      to the oral cavity for 7 days and then closed with a cotton pellet and zinc-oxide
      eugenol and glass ionomer cement. The animals were sacrificed one year after the
      experiment and prepared for histological examination of periradicular tissue
      responses to uninfected and infected devitalized pulp tissues. The results
      indicate that uninfected devitalized pulp tissues did not continuously release
      inflammatory mediators and cause persistent periradicular inflammation over a
      period of one year. However, infected devitalized pulp tissues induced various
      degrees of periradicular inflammation. Only the apical few millimeters of
      uninfected devitalized pulp tissue in the root canals were organized by
      granulation tissue from vital periodontal ligament tissue.

PMID- 16410066
TI  - Effects of proinflammatory cytokines on the expression of mineralization markers
      and heme oxygenase-1 in human pulp cells.
AB  - The roles of IL-1alpha and TNF-alpha in early pulp inflammation were investigated
      by determining the alkaline phosphatase (ALP) activity, the osteonectin (ON),
      osteocalcin (OC), bone sialoprotein (BSP), and heme oxygenase-1 (HO-1) expression
      using an immunoblot method. Primary cultured dental pulp cells were treated with
      IL-1alpha, TNF-alpha, or both for 3, 7, and 14 days. The pulp cells treated with
      IL-1alpha for 3 days showed elevated ALP activity and increased ON, OC, and HO-1
      expression, whereas TNF-alpha treatment did not increase the ALP activity and no
      BSP was expressed until day 14. The pulp cells treated with both IL-1alpha and
      TNF-alpha for 3 days showed increased HO-1 expression compared with that of the
      control. These data suggest that IL-1alpha and TNF-alpha produced in the early
      inflammatory reaction have different functions in human pulp cells. IL-1alpha
      induces ALP, ON, and OC in tooth mineralization and it may play a role in the
      cytoprotection of pulp cells via HO-1 expression, while long-term treatment of
      TNF-alpha may inhibit the tooth mineralization.

PMID- 16410067
TI  - A simple etching technique for improving the retention of fiber posts to resin
      composites.
AB  - Coupling of fiber posts to composites is hampered by absence of chemical union
      between epoxy resins and methacrylate-based resins. This study examined a
      clinically feasible protocol for creating micromechanical retention on the
      surface of fiber posts, using hydrogen peroxide etching to remove the surface
      layer of epoxy resin. This was followed by silanization of the exposed quartz
      fibers to enhance their chemical bonding to composites. Etching with 24% H2O2 for
      10 min or 10% H2O2 for 20 min produced a 50 microm thick surface zone that is
      depleted of epoxy resin, leaving intact, undamaged quartz fibers for
      silanization. Low viscosity flowable composites were employed to infiltrate this
      zone, to simulate the creation of hybrid layers in acid-etched dentin by dentin
      adhesives. Interfacial strengths were enhanced with the adjunctive use of H2O2
      etching and silanization, and were probably dependent on the ability of the
      flowable composites to completely infiltrate this interdiffusion zone.

PMID- 16410068
TI  - A comparison of three methods for preparing centered platforms around separated
      instruments in curved canals.
AB  - This study compared three methods for creating the most centered staging platform
      (SP) around separated instruments (SI) in curved canals. Green .04 ProFiles,
      notched at D(3), were separated in the apical third of 42 mesiobuccal canals of
      maxillary and mandibular molars. Teeth were divided into three groups. SPs were
      prepared in group 1 with Gates Gliddens (GG) to a size #3; group 2 with
      LightSpeed to a size 90; and group 3 with incrementally cut rotary .06 ProFiles
      to size 82. Pre- and postoperative digital radiographs were imported into AutoCAD
      to measure the deviation of SP from the head of the separated instrument.
      Pearson's correlation showed a positive relationship between deviation of the SP
      and the distance of the SI from the elbow of the canal. ANOVA showed that
      LightSpeed instruments were significantly more effective in preparing a centered
      staging platform around separated instruments in curved canals when compared to
      GG drills and ProFiles (p < 0.05).

PMID- 16410069
TI  - Spreader penetration during lateral compaction of resilon and gutta-percha.
AB  - Resilon, a thermoplastic, polyester polymer-based filling material, is a new
      material used for sealing root canals after chemomechanical preparation. The
      purpose of this in vitro study was to compare nickel-titanium (NiTi) spreader
      penetration in root canals having a .04 taper preparation using .02 and .04
      tapered master gutta-percha cones and .02 and .04 tapered master Resilon cones.
      Twenty canals, from extracted human teeth, were cleaned and shaped to a
      standardized 40/.04 size. Master cones of .02 or .04 tapered gutta-percha and .02
      or .04 tapered Resilon were placed in each canal. A fine-fine NiTi spreader was
      then placed next to the master cone with a 1.5-kg force. The penetration depth
      was measured, subtracted from working length, and recorded. A significant
      difference in penetration depth (p < 0.01) was found for both taper of the cone
      and material used. The depth of spreader penetration from greatest to least was
      .02 tapered Resilon, .02 tapered gutta-percha, .04 tapered Resilon, and .04
      tapered gutta-percha.

PMID- 16410070
TI  - Cyclic fatigue of three types of rotary nickel-titanium files in a dynamic model.
AB  - The cyclic fatigue resistance of three types of nickel-titanium rotary files was
      compared in a model using reciprocating axial movement. The influence of file
      size and taper was also investigated and fracture patterns were examined under
      SEM. The 10 experimental groups consisted of ProFiles, K3s, and RaCe files, size
      25 in .04 and .06 tapers, as well as ProFiles and K3s, size 40 in .04 and .06
      tapers. Each file was rotated freely at 300 rpm inside a stainless steel tube
      with a 60 degree and 5 mm radius of curvature. A continuous 3 mm oscillating
      axial motion was applied at 1 cycle per second by attaching an electric dental
      handpiece to the most inferior load cell of an Instron machine using a custom
      made jig. The number of rotations to failure was determined and analyzed using
      analysis of variance and Tukey's post hoc tests. Overall, K3 25/.04 files were
      significantly more resistant to cyclic fatigue compared to any other group in
      this study. In the 25/.04 category, K3s were significantly more resistant to
      failure than ProFiles and RaCe files. Also in the same category, ProFiles
      significantly outlasted RaCe files. In the 25/.06 group, K3s and ProFiles were
      significantly more resistant to failure than RaCe files, but K3s were not
      significantly different than ProFiles. In the 40/.04 and 40/.06 groups, K3s were
      significantly more resistant to cyclic fatigue than ProFiles. SEM observations
      demonstrated mostly a ductile mode of fracture. The results suggest that
      different cross-sectional designs, diameters, and tapers all contribute to a
      nickel-titanium instrument's vulnerability to cyclic failure.

PMID- 16410072
TI  - Comparison of defects in ProFile and ProTaper systems after clinical use.
AB  - The purpose of this study was to compare the incidence and mode of instrument
      separation of the two nickel-titanium (NiTi) rotary systems that were used
      according to a predefined schedule of clinical use by the same group of
      operators. A total of 166 ProFile and 325 ProTaper instruments, discarded from
      this endodontic clinic over 17 months, was analyzed. The incidences of instrument
      separation were 7% for ProFile and 14% for ProTaper (p < 0.05). The proportion of
      unwinding defects was 5% in ProFile and 0.3% in ProTaper instruments (p < 0.01).
      Flexural fatigue was implicated in the majority of separations in both groups.
      The results of this study indicated that while ProTaper was more likely to
      separate without warning, ProFile tended to exhibit unwinding of flutes more
      frequently.

PMID- 16410071
TI  - The effects of sodium hypochlorite (5.25%), Chlorhexidine (2%), and Glyde File
      Prep on the bond strength of MTA-dentin.
AB  - The purpose of this study was to evaluate the effects of sodium hypochlorite
      (5.25%), chlorhexidine (2%), and Glyde File Prep on the bond strengths of MTA
      dentin in vitro. Standardized dentin disks were prepared and the central hole in
      each disk was filled with mineral trioxide aggregate (MTA). The specimens were
      randomly divided into four groups to be immersed in saline, 5.25% NaOCl, 2%
      chlorhexidine, and Glyde File Prep for 2 hours. The bond strengths of MTA-dentin
      were measured with a material testing system (MTS) and the fractured surfaces on
      the root walls were observed by scanning electron microscopy. Compared with the
      control group, the bond strengths were significantly lower in Glyde File Prep
      group (p < 0.05) and there was no significant difference in the chlorhexidine
      group or in the NaOCl group (p > 0.05). This study suggested that Glyde File Prep
      could negatively affect the bond strengths of MTA-dentin.

PMID- 16410073
TI  - The quantitative evaluation of apical sealing of four endodontic sealers.
AB  - The aim of this in vitro study was to evaluate the apical seal obtained with four
      root canal sealers: Rocanal 2, Sealapex, AH Plus, and RC Sealer. Forty root
      canals were prepared using the step-back technique. The specimens were divided
      into four groups of 10 samples and obturated by laterally condensed gutta-percha
      with one of the tested sealers. The computerized fluid filtration method was used
      for evaluation of apical sealing properties. The quantitative apical leakage of
      each specimen was measured after 7, 14, and 21 days. Statistical analysis
      indicated that the apical leakage of all sealers used in this study decreased
      gradually from 7 days to 21 days (p < 0.05). Sealapex showed better apical
      sealing than the other sealers at 7, 14, and 21 days (p < 0.05). RC Sealer, AH
      Plus, and Rocanal 2 showed similar apical leakage values at every period (p >
      0.05).

PMID- 16410074
TI  - Internal resorption treated with mineral trioxide aggregate in a primary molar
      tooth: 18-month follow-up.
AB  - Mineral trioxide aggregate (MTA) repair of a mandibular second-primary molar
      tooth with an inflammatory resorptive defect in the coronal third of the root
      canal is reported in this case. After the root canals were obturated with zinc
      oxide eugenol sealer, MTA was applied to the resorption cavity. The coronal
      cavity was then restored with a stainless steel crown. At an 18-month follow-up,
      the tooth was asymptomatic clinically and radiographically. According to this
      result, it can be concluded that MTA may be a suitable material for use in the
      treatment of internal resorption in the coronal third of the root canal in
      primary teeth.

PMID- 16410075
TI  - p63 protein is essential for the embryonic development of vibrissae and teeth.
AB  - Development of skin appendages strongly depends on epithelial-mesenchymal
      interactions. One of the genes involved in this process is p63, a member of the
      p53 family of transcription factors, essential for ectodermal development, as
      elucidated by the phenotype of p63 knock-out mice. Surprisingly, no information
      on p63 expression in tooth and hair is yet available. Here, we show p63
      expression during teeth and vibrissae morphogenesis in mouse embryos and we also
      show a correlation with the expression patterns of the epithelial marker keratin
      5 and the proliferation marker Ki67. Our results show that p63 colocalizes with
      both K5 and Ki67 in the epithelium of developing vibrissae, while in teeth p63 is
      expressed, together with K5, in the undifferentiated ectoderm (enamel organ), and
      in ameloblasts, a subpopulation of differentiated ectodermal cells. Moreover, p63
      expression in tooth seems not to be fully colocalized with nuclear Ki67
      expression.

PMID- 16410077
TI  - Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis.
AB  - Rab GTPases are regulators of membrane trafficking that cycle between active (GTP
      bound) and inactive (GDP-bound) states. In this study, we report the
      identification of a new human Rab5 guanine nucleotide exchange factor (GEF),
      which we have named RAP6 (Rab5-activating protein 6). RAP6 contains a Rab5 GEF
      and a Ras GAP domain. We show that the Vps9 domain is sufficient for the
      interaction of RAP6 with GDP-bound Rab5 and that RAP6 stimulates Rab5 guanine
      nucleotide exchange. We also find that the Ras GAP domain of RAP6 shows GAP
      activity for Ras. Immunofluorescence experiments reveal that RAP6 is associated
      with plasma membrane and small intracellular vesicles that also contain Rab5.
      Additionally, the overexpression of RAP6 affects both fluid phase and receptor
      mediated endocytosis. This study is the first to show that RAP6 is a novel
      regulator of endocytosis that exhibits GEF activity specific for Rab5 and GAP
      activity specific for Ras.

PMID- 16410076
TI  - All-trans retinoic acid inhibited chondrogenesis of mouse embryonic palate
      mesenchymal cells by down-regulation of TGF-beta/Smad signaling.
AB  - Chondrogenesis is a critical step in palatogenesis. All-trans retinoic acid
      (atRA), a vitamin A derivative, is a known teratogenic effector of cleft palate.
      Here, we evaluated the effects of atRA on the osteo-/chondrogenic differentiation
      of mouse embryonic palate mesenchymal (MEPM) cells. MEPM cells, in a high-density
      micromass environment, undergo active chondrogenesis in a manner analogous to
      that of limb-derived mesenchymal cells, and served as a valid model system to
      investigate the mechanisms regulating chondrogenesis during palatogenesis. atRA
      treated MEPM micromass expressed relatively higher levels of osteoblastic gene
      markers (alkaline phosphatase and collagen type I) and lower levels of
      chondrocytic gene markers (collagen type II and aggrecan). As transforming growth
      factor-beta3 (TGF-beta3) is an essential growth factor for chondrogenesis of
      embryonic mesenchymal cells both in in vivo and in vitro conditions, we thereby
      explored the effects of atRA on TGF-beta3 signaling pathway. atRA led to an
      increase in mRNA expression of TGF-beta3 and an instantaneous decrease in TGF
      beta type II receptor (TbetaRII) as determined by real-time RT-PCR. Further study
      showed that atRA inhibited phosphorylation of Smad2 and Smad3 and increased Smad7
      expression. Activation of the Smad pathways by transfection with Smad7deltaC
      mutant or constitutively active TbetaRII retroviral vector abolished atRA-induced
      inhibition of chondrogenesis as indicated by Alcian blue staining, indicating
      that Smad signaling is essential for this response. Taken together, these data
      for the first time demonstrated a role for RA-induced hypochondrogenesis through
      regulation of the TGF-beta3 pathway and suggested a role for TbetaRII /Smad in
      retinoid-induced cleft palate.

PMID- 16410078
TI  - Vascular endothelial growth factor signalling in endothelial cell survival: a
      role for NFkappaB.
AB  - Angiogenesis is the development of blood capillaries from pre-existing vessels.
      Vascular endothelial growth factor (VEGF) is a key regulator of vessel growth and
      regression, and acts as an endothelial survival factor by protecting endothelial
      cells from apoptosis. Many genes involved in cell proliferation and apoptosis are
      regulated by the nuclear factor kappa B (NFkappaB) transcription factor family.
      This study aimed to address the hypothesis that VEGF-mediated survival effects on
      endothelium involve NFkappaB. Using an NFkappaB-luciferase reporter adenovirus,
      we observed activation of NFkappaB following VEGF treatment of human umbilical
      vein endothelial cells. This was confirmed using electrophoretic mobility shift
      assay and found to involve nuclear translocation of NFkappaB sub-unit p65.
      However, NFkappaB activation occurred without degradation of inhibitory IkappaB
      proteins (IkappaBalpha, IkappaBbeta, and IkappaBepsilon). Instead, tyrosine
      phosphorylation of IkappaBalpha was observed following VEGF treatment, suggesting
      NFkappaB activation was mediated by degradation-independent dissociation of
      IkappaBalpha from NFkappaB. Adenovirus-mediated over-expression of either native
      IkappaBalpha, or of IkappaBalpha in which tyrosine residue 42 was mutated to
      phenylalanine, inhibited induction of NFkappaB-dependent luciferase activity in
      response to VEGF. Furthermore, VEGF-induced upregulation of mRNA for the anti
      apoptotic protein Bcl-2 and cell survival following serum withdrawal was reduced
      following IkappaBalpha over-expression. This study highlights that different
      molecular mechanisms of NFkappaB activation may be involved downstream of stimuli
      which activate the endothelial lining of blood vessels.

PMID- 16410079
TI  - Emergency thoracotomy in thoracic trauma-a review.
AB  - Thoracic trauma is one of the leading causes of death in all age groups and
      accounts for 25-50% of all traumatic injuries. While the majority of patients
      with thoracic trauma can be managed conservatively, a small but significant
      number requires emergency thoracotomy as part of their initial resuscitation. The
      procedure has been advocated for evacuation of pericardial tamponade, direct
      control of intrathoracic haemorrhage, control of massive air-embolism, open
      cardiac massage and cross-clamping of the descending aorta. Emergency thoracotomy
      can be defined as thoracotomy "occurring either immediately at the site of
      injury, or in the emergency department or operating room as an integral part of
      the initial resuscitation process". Following emergency thoracotomy, the overall
      survival rates for penetrating thoracic trauma are around 9-12% but have been
      reported to be as high as 38%. The survival rate for blunt trauma is
      approximately 1-2%. The decision to perform emergency thoracotomy involves
      careful evaluation of the scientific, ethical, social and economic issues. This
      article aims to provide a review of the current literature and to outline the
      pathophysiological features, technical manoeuvres and selective indications for
      emergency thoracotomy as a component of the initial resuscitation of trauma
      victims with thoracic injury.

PMID- 16410081
TI  - Bilateral adrenal neuroblastoma and nephroblastoma occurring synchronously in a
      child with Fanconi's anemia and VACTERL syndrome.
AB  - Fanconi's anemia (FA) is an autosomal recessive inherited syndrome with a
      predisposition to malignancy. The association between FA and solid pediatric
      tumors is extremely rare. The authors report a rare case of VACTERL syndrome
      associated with FA and multiple solid pediatric tumors occurring in a very young
      girl. This child had numerous congenital anomalies (horseshoe kidney, cerebella
      hypoplasia, microcephaly, sacral agenesis) and esophageal atresia, which was
      repaired in neonatal period. Such association led quickly to the diagnosis of FA.
      At age of 11 months, she developed simultaneously a renal tumor in a horseshoe
      kidney and bilateral adrenal tumors. The left adrenal mass was removed, and
      partial nephrectomy was performed. Histological analysis concluded to adrenal
      neuroblastoma and nephroblastoma. We also evaluated the c-kit expression in these
      tumors to propose a therapeutic alternative to chemotherapy by oral agent STI-571
      (Gleevec; Novartis, East Hanover, NJ). Strong cytoplasmic immunostaining of c-kit
      was found in both tumors. Unfortunately, she quickly developed a posterior
      cerebellar fossa tumor and died 1 month later. This clinical situation is very
      rare but suggests that young patients with FA and solid pediatric tumors may
      belong to a particular subgroup of FA. Further studies are necessary to test if
      STI-571 treatment could be efficient in such patients with pediatric tumors.

PMID- 16410080
TI  - Fibrobronchoscopic treatment of foreign body aspiration in children: an
      experience of 5 years in Hangzhou City, China.
AB  - OBJECTIVE: The aims of the study were to evaluate duration of symptoms, clinical
      manifestation, radiological findings, fibrobronchoscopic findings, and the
      complications of airway foreign body (FB). METHODS: A retrospective review of 304
      children who had airway FB removed via fibrobronchoscopy from January 1997 to
      June 2003 was conducted in the Children's Hospital of Zhejiang University School
      of Medicine, China. Two hundred eight boys and 96 girls were included. Their ages
      ranged from 2 months to 11 years, and the median was 18 months. RESULTS: Three
      patients died; 81.24% of the patients had a history of FB aspiration, and the
      most frequent clinical manifestation was paroxysmal coughing (89.25%). Positive
      radiological findings were found in 90.13% of patients, and the most common type
      of FB was peanut (35.53%). Serious complication of lung was found in 65 patients,
      and the associated factors were age, sex, and times of fibrobronchoscopy and
      location of FB in the right or left lung. CONCLUSIONS: FB aspiration remains a
      major cause of morbidity and mortality in childhood. Education aimed at
      increasing diagnostic acumen of the physicians and heightening of public
      awareness are the most important steps needed to reduce the morbidity and
      mortality.

PMID- 16410082
TI  - An 11-year-old male patient demonstrating cholangiocarcinoma associated with
      congenital biliary dilatation.
AB  - We herein report an 11-year-old male patient demonstrating advanced
      cholangiocarcinoma associated with congenital biliary dilatation (CBD). This
      Japanese boy presented with abdominal pain lasting a few days, and a diagnosis of
      type IV-A CBD was made based on the findings of imaging studies using
      ultrasonography, computed tomography, and magnetic resonance imaging. These
      studies also revealed a wide flat lesion associated with a few small round masses
      in the dilated choledochus. Intraoperative cholangiography revealed the presence
      of pancreaticobiliary maljunction of CP type. Malignant cells were found in
      biopsy specimens from both the flat and polypoid lesions. Because the distal
      stump of choledochus at anomalous confluent to the pancreatic duct also showed
      malignant cells, a pyloric preserved pancreaticoduodenectomy with lymph node
      dissection was thus performed. Lymph node metastasis was found in one of the
      mesenteric lymph nodes, and vascular invasion was also found in the main tumor
      lesions of the dilated bile duct. The postoperative course was uneventful, and
      the patient has been followed with chemotherapy as an outpatient without any
      evidence of recurrence. To our knowledge, this report is the youngest case of
      cholangiocarcinoma associated with CBD.

PMID- 16410083
TI  - Extensive cervical-mediastinal cystic lymphatic malformation treated with
      sclerotherapy in a child with Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay syndrome is a rare congenital disorder characterized by
      combined vascular malformations, varicosities, and limb enlargement. A child case
      of Klippel-Trenaunay syndrome with a large cervicomediastinal cystic lymphatic
      malformation and a vascular mass on the chest wall has been presented to
      demonstrate combined use of conservative and surgical approaches in this
      syndrome. Cystic lymphatic malformation was treated by sclerotherapies including
      ultrasound-guided transthoracic bleomycin injection into mediastinal cyst, which
      was tried for the first time in the literature, and vascular chest wall tumor
      necessitated surgical excision.

PMID- 16410084
TI  - Total laparoscopic left lateral sectionectomy performed in a child with benign
      liver mass.
AB  - Despite the increasing number of recent reports on laparoscopic liver resection
      in adults, there are only rare reports on such a procedure being performed in
      children. The authors report here on a total laparoscopic left lateral
      sectionectomy that was performed in a 5-year-old girl who had a cystic tumor of
      the liver. The operative time was 150 minutes, the estimated blood loss was about
      100 mL, and no intraoperative transfusion was required. The patient was
      discharged on postoperative day 11 without any significant complications. The
      postoperative pathology of the specimen confirmed it to be a mesenchymal
      hamartoma of the liver with a disease-free resection margin. This case
      demonstrates that laparoscopic liver resection can be a safe and feasible
      operative procedure for the pediatric patient with liver disease.

PMID- 16410085
TI  - Kasabach-Merritt syndrome: dangers of interferon and successful treatment with
      pentoxifylline.
AB  - A girl aged 3 months presented with thrombocytopenia and bruising around a large
      vascular malformation of her posterior abdominal wall. Treatment was started with
      corticosteroids and platelet replacement, but with no improvement and a platelet
      count persistently less than 10 x 10(9)/L over 3 weeks, alpha-interferon was
      added. There was an immediate increase in bruising, a fall in platelet count, and
      an increase in platelet transfusion requirement until interferon was discontinued
      11 days later. After a further week, the platelet count returned to the levels
      before interferon, but the patient did not develop any further symptoms. The
      platelet count remained low with no clinical change until pentoxifylline was
      started at the age of 15 months. The platelet count rose to 117 x 10(9)/L within
      4 days and remained more than 100 x 10(9)/L thereafter. The patient is now 7
      years old and has had no recurrence since stopping the pentoxifylline at the age
      of 5 years. Although thrombocytopenia is a recognized side effect of interferon
      therapy, this very dangerous complication has not been previously reported using
      interferon for the Kasabach-Merritt syndrome.

PMID- 16410086
TI  - Nodular periorchitis masquerading as a malignant parafunicular tumor in an
      adolescent.
AB  - We report on a case of nodular periorchitis, an uncommon perifunicular mass in a
      13-year-old adolescent accompanied by contralateral hydrocele. Nodular
      periorchitis is a rare, fibroproliferative, benign mesenchymal neoplasm of the
      paratesticular tissues of the scrotum with a low risk for recurrence. Testis
      preserving surgery is the treatment of choice.

PMID- 16410087
TI  - Diaphragmatic lipoma in a 4-year-old girl: a case report.
AB  - A lipoma of the diaphragm is extremely rare. Although most congenital
      diaphragmatic lipomas are encountered in middle or old age because of their
      typical asymptomatic nature, none have been reported in patients younger than 14
      years. We report the case of a large diaphragmatic lipoma in a 4-year-old
      patient.

PMID- 16410088
TI  - Retroperitoneal hemangioma of infancy.
AB  - A premature infant presented with an incidental finding of a mass in the
      retroperitoneum adjacent to the adrenal gland seen on a renal ultrasound study. A
      clinical diagnosis of neuroblastoma was made based on imaging and laboratory
      studies; however, upon resection, histological examination revealed a cellular
      capillary hemangioma of infancy. Hemangioma should be considered in the
      differential diagnosis of asymptomatic retroperitoneal mass lesions in infants.

PMID- 16410089
TI  - Lumbosacral parasitic rachipagus twin.
AB  - A rare case of a newborn girl presenting with a mass representing an aborted
      parasitic twin attached to the back in the midline over the lumbosacral region
      (parasitic rachipagus) is reported. Rudimentary digits were attached to the mass,
      and in one area, the overlying skin resembled scrotal skin. A depression
      resembling an anal dimple was also present on the surface of the mass.
      Investigations showed a well-developed long bone and other small bones within the
      parasite, and sacral spina bifida in the autosite. Successful surgical excision
      of the parasitic mass was performed. A review of the literature pertaining to
      parasitic rachipagus twinning is presented.

PMID- 16410090
TI  - Malignant vascular tumors of liver in neonates.
AB  - Malignant vascular tumors of the liver are rare in children, especially in
      neonates. We report two cases. One was initially diagnosed as infantile
      hemangioendothelioma. Rapid growth and appearance of pulmonary metastasis while
      on aggressive medical treatment suggested malignant transformation. The other
      neonate presented with intractable ascites and liver biopsy showed histological
      features of angiosarcoma. Ascites has rarely been reported as a presenting
      feature of angiosarcoma in literature. Both patients died. To date, surgery,
      chemotherapy, and radiotherapy have not improved the outcome of malignant
      vascular tumors of liver.

PMID- 16410091
TI  - Management of splenic abscess in children by percutaneous drainage.
AB  - BACKGROUND/PURPOSE: Isolated splenic abscesses are rare in pediatric patients.
      The recommended treatment in the literature has been in favor of splenectomy,
      although conservative treatment with splenic preservation is being increasingly
      reported. We report successful management of 4 pediatric patients with splenic
      abscess by needle aspirations and antibiotics. MATERIALS AND METHODS: Four
      children (aged 7-11 years; male-female, 3:1) were admitted in our institution
      with history of high-grade fever with chills, anorexia, left hypochondrial pain,
      and splenomegaly. One child was a known case of thalassemia, and one had a
      history of typhoid fever. The others did not have any predisposing condition.
      Ultrasonography (USG) and computed tomographic scan of the abdomen showed a
      solitary abscess in the spleen in 2 patients and multiple abscesses in the other
      2. Ultrasonography-guided needle aspiration in 3 cases revealed purulent fluid,
      which, on culture, grew Escherichia coli in 1 case, Salmonella paratyphi A in 1
      case, but sterile in 1 case. Blood culture was sterile in all the cases, but
      Widal's test was positive in 2 patients. Treatment protocol included USG-guided
      needle aspiration of pus along with intravenous ceftriaxone, metronidazole, and
      amikacin for 3 to 12 weeks. RESULTS: All 4 patients showed a good response to
      conservative treatment. Serial USG showed gradual resolution of abscess, and none
      was subjected to splenectomy. CONCLUSION: Isolated splenic abscess in children
      can be successfully treated with needle aspirations and intravenous antibiotics,
      thereby avoiding splenectomy.

PMID- 16410092
TI  - Laparoscopic repair of neonatal gastric perforation.
AB  - BACKGROUND: Gastric perforation is a rare, life-threatening condition in
      neonates. To avoid deterioration, prompt surgical treatment is mandatory.
      PATIENTS: We report on 2 neonates (1 and 8 days old) with feeding tube associated
      gastric perforation managed laparoscopically by single layer suture repair. Both
      children suffered from severe peritonitis. Operative time was 60 minutes in both
      cases. Oral feeding was started on postoperative day 3 and 7, respectively. No
      complications regarding the gastric perforation were encountered on follow-up (11
      and 8 months, respectively) in both cases. CONCLUSIONS: We recommend laparoscopic
      suture repair as a safe and feasible method for surgical treatment of gastric
      perforation in neonates. These appear to be the first reported cases using this
      procedure for treatment of neonatal gastric perforation.

PMID- 16410093
TI  - Giant T-shaped duplication of the transverse colon. A case report.
AB  - A case of long diverticular colonic duplication producing acute abdominal pain in
      a 6-year-old girl is presented. Physical examination showed no signs of acute
      abdomen at the initial presentation. After a pain-free interval, there was a
      sudden onset of severe abdominal pain and a large tumor in the lower abdomen was
      observed. A plain x-ray showed an enormously dilated colonic pouch filled with
      gas. Excision of the T-shaped duplication and small part of the transverse colon
      was successful. Because of extensive fibrotic changes in the colon near the
      opening of duplication, a resection margin of at least 2 cm is recommended.

PMID- 16410094
TI  - Pediatric cystadenoma of the mesocolon.

PMID- 16410095
TI  - Endobronchial migration of prosthetic patch after congenital diaphragmatic hernia
      repair.
AB  - Surgical repair of congenital diaphragmatic hernia (CDH) can be performed by
      means of either direct suturing of the diaphragm or positioning of a prosthetic
      patch. However, half of all prosthetic patches show evidence of reherniation. We
      describe the case of an 8-year-old girl who presented with prosthesis dislocation
      and fistulization in the right lower bronchus as a complication of a CDH repair
      that she underwent when she was 1 year old. Abdominal ultrasound and magnetic
      resonance imaging suggested a hernia relapse, whereas chest computed tomographic
      scan failed to identify the diaphragmatic defect. Only fibrobronchoscopy allowed
      fistulization of the prosthesis into the bronchi to be correctly diagnosed.

PMID- 16410096
TI  - A new case of male Y-type urethral duplication and review of literature.
AB  - Urethral duplication is a rare congenital anomaly, affecting mainly boys.
      Generally, the duplication develops on the sagittal plane; the accessory urethra
      may run dorsally or ventrally to the orthotopic one. The embryology of this
      pathology is still controversial. In the English medical literature,
      approximately 175 cases have been reported. We report here a new case of urethral
      duplication type II A2 "Y" in a 14-year-old boy and review the current literature
      of this rare entity.

PMID- 16410097
TI  - Penile torsion repair by suturing tunica albuginea to the pubic periosteum.
AB  - PURPOSE: The aim of the study was to evaluate the effectiveness of a new
      technique to repair penile torsion in children. METHODS: Eighteen boys with
      penile torsion were evaluated in our department from 1989 to 2003. Eleven had
      associated hypospadias, 4 had chordee without hypospadias, and 3 had torsion
      only. The direction of rotation was counterclockwise in 16 cases and clockwise in
      2 cases. Torsion was repaired in 6 patients by degloving the penis and
      reattaching the dartos and the skin (comparative group). In 11 patients (1 with
      prior repair), the torsion was corrected by suturing the lateral edge of the
      corpus cavernosum to the pubic periosteum (study group). Two patients were not
      treated. RESULT: Follow-up ranges from 6 months to 7 years. All of the 11 cases
      in the study group had satisfactory correction of the penile torsion. All of the
      urethroplasties for hypospadias were successful. In the comparative group, none
      of 6 patients had satisfactory correction of the rotation. CONCLUSION: The
      technique of degloving the penis and reattaching the skin cannot reliably correct
      penile torsion in our experience. Lateral suturing of tunica albuginea to the
      pubic periosteum to repair penile torsion appears to be a better technique.

PMID- 16410100
TI  - "The ultimate commencement".

PMID- 16410101
TI  - Is continuation of life support always the best option for neonates with
      congenital anatomical anomalies?

PMID- 16410102
TI  - Birth weight and McGoon Index predict mortality in newborn infants with
      congenital diaphragmatic hernia.
AB  - BACKGROUND: Despite improvements in clinical management, mortality of congenital
      diaphragmatic hernia (CDH) remains high. Early prediction of mortality risk helps
      in comparing strategies and/or performances of different centers. Birth weight
      (BW), Apgar Score at 5 minutes, and modified McGoon Index (MGI) calculated by the
      ratio between the diameters of pulmonary arteries and the descending aorta have
      been used to determine mortality of CDH. AIM: The purpose of this study is to
      evaluate the relationship between early detectable variables and survival in
      newborns with CDH intubated at birth, managed with "gentle" ventilation and
      delayed surgery. METHODS: All medical records of patients affected by high-risk
      CDH and treated with a standardized protocol at Bambino Gesu Children's Hospital,
      Rome, Italy, between January 2002 and September 2004 were reviewed. Prenatal
      diagnosis, gestational age, BW, sex, side of hernia, and MGI were recorded on
      admission. The relationship with mortality of each variable was evaluated by
      univariate analysis. Subsequently, a predictive model of mortality was developed
      using a logistic regression: the explanatory variables, BW, and MGI were
      dichotomized in high (HBW and HMGI) and low (LBW and LMGI) according to the best
      cutoff found with receiver-operating characteristic curves. RESULTS: Thirty-four
      newborns with CDH, treated with a standardized protocol, were studied. The main
      characteristics of the 34 patients were BW, 2886 g (1500-3620 g); gestational
      age, 37.7 weeks (32-42 weeks); male/female, 22/12; right/left, 8/26; prenatal
      diagnosis, 29; MGI, 1.31 (0.9-1.85). Only BW and MGI were significantly (P < .05)
      associated with mortality at the univariate analysis. The best cutoff values were
      2755 g for BW (sensitivity, 70%; specificity, 74%) and 1.25 for MGI (sensitivity,
      73%; specificity, 78%). Using these limits, BW and MGI resulted independently
      associated with mortality in the multivariate analysis. Using the 4 possible
      combinations, the LBW associated with the LMGI presented the highest prediction
      of mortality (80%). CONCLUSIONS: Birth weight and MGI, variously combined, were
      predictive of mortality. Because they are not influenced by subsequent modalities
      of care, they can be considered as valid early severity scores in CDH and used
      for comparing strategies and/or performances of different centers.

PMID- 16410103
TI  - Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore
      Tex.
AB  - PURPOSE: The sequelae of congenital diaphragmatic hernia (CDH) continue well
      beyond the perinatal period. Up to 50% of these patients have subsequent
      recurrent herniation or small bowel obstruction (SBO). A recent trend has been
      toward the use of bioactive prosthetic materials. We reviewed different patch
      closure techniques used for CDH repair at our institution and their association
      with these sequelae. METHODS: A retrospective review was performed of 152 records
      for patients with CDH. Newborns that underwent patch repair for CDH and survived
      for at least 30 days were included in the analysis. Primary outcomes evaluated
      were recurrent herniation and SBO. Two types of prostheses were examined, Gore
      Tex, an artificial material, and Surgisis, a bioactive material. RESULTS: Twelve
      (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen
      (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two
      additional patients in each group presented with SBO. No significant difference
      in recurrent herniation rates was observed (P > .5). The time to recurrence was
      similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis,
      76% Gore-Tex) occurring in the first year. CONCLUSION: The rates of recurrent
      herniation and SBO after neonatal prosthetic patch repair of CDH were similar
      regardless of the prosthetic material used (Surgisis or Gore-Tex).

PMID- 16410105
TI  - Nonoperative management of pectus carinatum.
AB  - BACKGROUND: Although surgery has been the mainstay of treatment of
      chondrogladiolar pectus carinatum (PC), several authors have advocated the
      benefits of nonoperative approaches to induce chest wall remodeling. Based on our
      initial success with compression bracing, we have integrated this modality into
      our treatment algorithm. METHOD: We reviewed the charts of all patients treated
      for PC at our pediatric hospital between 1997 and 2004. Patients were managed
      with observation, operative repair, and orthotic bracing that provides continuous
      anteroposterior sternal compression. The brace was worn for 14 to 16 hours per
      day until linear growth was complete or for a minimum of 2 years. RESULTS: One
      hundred patients were diagnosed with PC. Fifty-seven patients had no treatment
      and were monitored. Twenty-nine patients were fitted with a brace. Of these 29
      patients, 3 were noncompliant, resulting in a compliance rate of 90%. Of the
      remaining brace patients, all have had positive outcomes with no observed
      complications. Seventeen patients underwent surgical repair. Their outcomes were
      also positive with no major complications. CONCLUSION: Our findings clearly
      demonstrate that compression bracing is a safe and effective treatment for
      children with chondrogladiolar PC. We currently offer this approach as a first
      line treatment, reserving surgery for patients who are noncompliant and those who
      fail the nonoperative modality.

PMID- 16410104
TI  - Diaphragmatic repair through fetal tissue engineering: a comparison between
      mesenchymal amniocyte- and myoblast-based constructs.
AB  - PURPOSE: We have previously shown that fetal tissue engineering is a preferred
      alternative to diaphragmatic repair in a large animal model. This study was aimed
      at comparing diaphragmatic constructs seeded with mesenchymal amniocytes and
      fetal myoblasts in this model. METHODS: Neonatal lambs (n = 14) underwent repair
      of an experimental diaphragmatic defect with identical scaffolds, either seeded
      with labeled autologous cells (mesenchymal amniocytes in group 1 and fetal
      myoblasts in group 2) or as an acellular graft (group 3). At 1 to 12 months
      postoperatively, implants were harvested for multiple analyses. RESULTS: Repair
      failure (reherniation or eventration) was significantly higher in group 3 than in
      groups 1 and 2, with no difference between groups 1 and 2. Seeded fetal myoblasts
      quickly lost their myogenic phenotype in vivo. All grafts contained cells with a
      fibroblastic-myofibroblastic profile. Elastin concentrations and both modular and
      ultimate tensile strengths were significantly higher in group 1 than in groups 2
      and 3. There were no differences in glycosaminoglycans and type I collagen levels
      among the groups. CONCLUSIONS: Diaphragmatic repair with a mesenchymal amniocyte
      based engineered tendon leads to improved structural outcomes when compared with
      equivalent fetal myoblast-based and acellular grafts. The amniotic fluid is a
      preferred cell source for tissue-engineered diaphragmatic reconstruction.

PMID- 16410106
TI  - Use of a biodegradable patch for reconstruction of large thoracic cage defects in
      growing children.
AB  - BACKGROUND/PURPOSE: At our institution, procedures were developed to enlarge and
      stabilize the thoracic cavity of children born with severe-enough abnormalities
      of the thoracic cage as to result in lack of normal lung growth and function. In
      addition to the device known as the vertical expandable prosthetic titanium rib
      (VEPTR), some type of patch material was needed to cover large congenital defects
      of the chest cage owing to rib absence or to cover defects created because of the
      expansion process. Initially, synthetic material, polytetrafluorethylene (Gore
      Tex, WL Gore and Associates, Flagstaff, Ariz) was used, but this proved itself to
      be restrictive over time and required removal. Thus, a nonsynthetic biodegradable
      patch material was adopted for coverage of the defects (Surgisis, Cook,
      Bloomington, Ind). METHODS: From October 2001 through October 2004, 26 growing
      children undergoing thoracic cage reconstruction received the biodegradable
      extracellular matrix patch derived from porcine SIS (Cook). A patch was deemed
      necessary if any one of the following conditions was obtained: (a) herniation of
      the lung was likely; (b) chest wall musculature was significantly diminished; (c)
      injury to the lung was likely at reoperation; (d) the defect was greater than 2 x
      2 cm. RESULTS: During the follow-up period, 41 months thus far, each of the 26
      children has undergone routine, scheduled expansions or change-out procedures
      every 6 months. The SIS has not required removal for any reason and has not
      restricted growth of the thoracic cage. CONCLUSIONS: Compared with synthetic soft
      tissue patch material, the nonsynthetic, biodegradable soft tissue patch (SIS)
      has proven to be a superior alternative, thus far, to others for use in our
      population of patients for reconstruction of the thoracic cage in the growing
      child.

PMID- 16410107
TI  - Long-term follow-up after thymectomy for myasthenia gravis: thoracoscopic vs
      open.
AB  - PURPOSE: The aim of this study was to determine if patients are in remission or
      weaning off medication after thymectomy for myasthenia gravis (MG) and to examine
      the thoracoscopic versus open approaches. METHODS: A retrospective review of all
      patients who underwent thymectomy for MG at a tertiary referral center between
      1992 and 2004 (N = 14). Six patients (42.9%) underwent thoracoscopic resection.
      Eight patients underwent open resection; 5 (35.7%) had median sternotomy and 3
      (21.4%) by transcervical approaches. Follow-up was obtained in 12 (85.7%) of 14
      patients by both chart review and telephone. The mean follow-up was 43.0 months
      (range, 4-111 months). Statistical significance was determined by Student's t
      test or Fisher's Exact Test. RESULTS: The thoracoscopic group had a mean
      operating time of 138.8 minutes compared with 139.8 minutes in the open group (P
      = .9). The thoracoscopic group had a mean estimated blood loss of 7.5 mL compared
      with 52.5 mL in the open group (P = .02). The mean length of stay for the
      thoracoscopic group was 1.5 days (range, 1-2 days) and was 10.6 days (range, 3-41
      days) in the open group (P = .13). Three (60%) of 5 patients were entirely off
      medication in the thoracoscopic group at the time of follow-up compared with 3
      (50%) of 6 patients in the open group (P = 1.0). In the thoracoscopic group, 5
      (83.3%) of 6 were in class 1 to 3 of the DeFilippi classification (complete
      remission or improved with decreased medication requirements). One patient had no
      change in symptoms (class 4). In the open group, 5 (83.3%) of 6 were classified
      as DeFilippi 1 to 3 at the time of follow-up, and one patient had worsening
      symptoms (class 5). CONCLUSIONS: Both thoracoscopic and open approaches to
      thymectomy in patients with MG are effective, with more than 80% of patients in
      both groups in remission or with improvement at the time of follow-up. The
      thoracoscopic group has the added benefits of decreased estimated blood loss,
      decreased length of hospital stay, and improved cosmesis. We advocate the
      thoracoscopic approach for thymectomy in the treatment of juvenile MG.

PMID- 16410108
TI  - Esophageal strictures in children with recessive dystrophic epidermolysis
      bullosa: an 11-year experience with fluoroscopically guided balloon dilatation.
AB  - BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited
      blistering skin disorder that is associated with significant esophageal
      strictures, resulting in dysphagia and nutritional failure. Although
      endoscopically guided balloon dilatation is a widely used treatment, the use of
      an endoscope carries the risk of oropharyngeal trauma. To minimize this risk, we
      have eliminated its use. METHOD: We reviewed the charts of all RDEB patients who
      underwent balloon dilatation for esophageal strictures between August 1993 and
      March 2005. Balloon dilatation procedures were performed under anesthesia and
      with fluoroscopic control. RESULTS: We performed 92 dilatations on 25 RDEB
      patients. Most patients reported immediate relief of symptoms, rapid recovery,
      and resumption of adequate food intake within 1 day. The mean interval between
      dilatations was 1 year. Six patients (24%) have required only 1 dilatation, and 1
      of these 6 has had a dilatation-free interval of 25 months. One patient with a
      history of multiple dilatations has remained dilatation-free for 5 years. No
      procedure-related complications have occurred. CONCLUSIONS: Fluoroscopically
      guided balloon dilatation is a gentle, safe, effective, and repeatable technique
      that should be considered as a first line of treatment.

PMID- 16410109
TI  - Bronchial atresia: the hidden pathology within a spectrum of prenatally diagnosed
      lung masses.
AB  - PURPOSE: This study was aimed at determining whether different congenital lung
      masses represent diverse manifestations of a single developmental abnormality
      associated with fetal airway obstruction. METHODS: We conducted a 3-year
      retrospective review of patients who underwent surgical resection of a prenatally
      diagnosed lung mass. Prenatal imaging was used to define mass position and its
      effect on adjacent organs. Lung specimens were examined through careful full
      specimen microdissections, as well as by plain and contrast roentgenograms.
      RESULTS: Twenty-five patients underwent lung resection during this study period.
      Based on the final pathology reports, 56% were congenital cystic adenomatoid
      malformations, 12% were congenital lobar emphysemas, 8% were bronchopulmonary
      sequestrations, and 24% had features of both cystic adenomatoid malformation and
      bronchopulmonary sequestrations. No bronchogenic cysts were present in this
      series. Overall, bronchial atresia was identified in 77% of the examined
      specimens (n = 22) and was associated with all types of lung malformations.
      CONCLUSIONS: Bronchial atresia is a common, unrecognized component of prenatally
      diagnosed congenital cystic adenomatoid malformations, bronchopulmonary
      sequestrations, congenital lobar emphysemas, and lesions of mixed pathology. Most
      congenital lung masses may be part of a spectrum of anomalies linked to
      obstruction of the developing fetal airway as an underlying component in their
      pathogenesis.

PMID- 16410110
TI  - Prenatal presentation and outcome of children with pleuropulmonary blastoma.
AB  - BACKGROUND/PURPOSE: Pleuropulmonary blastoma (PPB) is a rare primary neoplasm of
      pleuropulmonary mesenchyme. Fewer than 170 children have been reported, and few
      single institutions have reported more than several cases. Treatment for this
      condition is primarily surgical resection; however, increasing experience
      suggests that adjuvant chemotherapy may decrease recurrence and improve outcome.
      METHODS: We reviewed the charts of all children with PPB treated at our
      institution since 1960. We reviewed the prenatal features, clinical presentation,
      operation, pathological findings, adjuvant treatment, and outcome. RESULTS: Ten
      children (6 boys and 4 girls) were treated for PPB at a mean age of 3.2 +/- 4.3
      years. In 2, a cystic lung mass was diagnosed prenatally, and in 8, a cystic or
      solid and cystic lung mass was diagnosed postnatally (right lung, 3; left lung,
      4; and bilateral, 3). In no patient was PPB considered preoperatively. Surgical
      resection was performed at 1 day to 11 years (median, 23 months) of age. Seven
      children had complete resection; 1 had microscopic residual disease, and 2 had
      gross residual disease. Pathology showed type I PPB in 7, type II in 1, and type
      III in 2. Five patients received adjuvant chemotherapy with vincristine,
      actinomycin, and cyclophosphamide-based regimens. At follow-up (mean, 7.7 +/-
      11.5 years; range, 1-456 months), children with type I PPB have no evidence of
      disease (n = 6) or are lost to follow-up (n = 1), whereas all those with type
      II/III PPB have died of the disease. CONCLUSIONS: PPB must be included in the
      differential diagnosis of a fetus, neonate, or child with a cystic lung mass.
      This finding supports early resection of these lesions rather than observation or
      treatment with nonoperative strategies.

PMID- 16410111
TI  - Diagnostic and therapeutic laparoscopy in pediatric abdominal trauma.
AB  - PURPOSE: The purpose of this study is to assess the role of emergent laparoscopy
      as a diagnostic and potentially therapeutic modality in pediatric trauma. We
      hypothesize that diagnostic laparoscopy provides important information for the
      treatment of children with abdominal trauma and is accompanied by improved
      diagnostic accuracy, reduction of nontherapeutic laparotomy rates, and a
      reduction of morbidity. METHODS: A 5-year (January 2000-December 2004)
      retrospective review of a pediatric level I trauma center database was performed
      after institutional review board approval was obtained, and information regarding
      patients who had operations for abdominal trauma was abstracted. Demographic
      variables, mechanism of injury, operative interventions, and patient outcomes
      were examined. Statistical analysis was performed using descriptive statistics
      and Student's t test (P < .05). RESULTS: There were 7127 trauma admissions, of
      which 113 had abdominal explorations for blunt (88%) and penetrating (12%)
      trauma. Thirty-two (28%) patients had laparoscopy performed. Laparotomy was
      avoided in 56% of these patients. Laparoscopic therapeutic interventions were
      performed in 6 (19%) patients. Laparoscopy assisted in the diagnosis and
      subsequent conventional repair of perforated viscera in 10, diaphragmatic rupture
      in 3, and distal pancreatic injury in 1. Patients who had a laparoscopic
      procedure of any kind were less severely injured leading to significantly lower
      number of intensive care unit (0.6 +/- 1.6, P = .0004) and hospital days (7.4 +/-
      5.6, P = .002) than patients who had a laparotomy (3.7 +/- 7.1 and 12.5 +/-
      11.4). No injuries were missed, or technical complications occurred, as a result
      of laparoscopic explorations. There were 6 deaths in the laparotomy group. No
      patients who underwent laparoscopy died. CONCLUSION: Laparoscopy in pediatric
      trauma is a safe method for the evaluation and treatment of selective blunt and
      penetrating abdominal injuries in hemodynamically stable patients. Laparoscopy
      serves as a diagnostic tool in abdominal trauma, which reduces the morbidity of a
      negative laparotomy.

PMID- 16410112
TI  - Isolated computed tomography diagnosis of pulmonary contusion does not correlate
      with increased morbidity.
AB  - BACKGROUND: Increased utilization of computed tomography (CT) has led to a rise
      in the diagnosis of pulmonary contusion. Its clinical significance, in the
      absence of findings on chest radiograph (CXR), has not been defined. This study
      examines the clinical course of patients with CT-only diagnosis of pulmonary
      contusion and compares it with that of patients with CXR-proven pulmonary
      contusion. METHODS: The trauma database identified all children undergoing chest
      CT for blunt thoracic trauma during a 3-year period. Records were reviewed for
      age, mechanism of injury, Injury Severity Score (ISS), length of hospital stay
      (LOS), need for intensive care unit admission, and need for endotracheal
      intubation. A pediatric radiologist reviewed all films in a blinded fashion.
      Statistical analysis was performed using analysis of variance and Fisher's Exact
      test for 2 x 3 tables. RESULTS: Eighty-two patients were identified. There were
      no CXR-positive, CT-negative cases. A CT diagnosis of pulmonary contusion was
      made in 46 patients. Of these, 31 had a contusion on CXR as well (CXR+ group) and
      15 had a normal CXR (CT+ only group). Mean ISS score did not differ significantly
      between the two groups (27 +/- 12.3 and 22 +/- 10.3, respectively). Thirty-six
      patients had a normal CT (control). Mean LOS was significantly longer in the CXR+
      group (13 +/- 12.0 days) than in the CT+ only and control groups (5 +/- 3.6 and 9
      +/- 9.5 days, respectively; P < .01). The percentages of children requiring
      intensive care unit admission and intubation were also significantly higher in
      the CXR+ group. CONCLUSION: The finding of pulmonary contusion by CT alone does
      not increase patient morbidity and appears to be of limited clinical
      significance.

PMID- 16410113
TI  - Decompressive craniectomy in pediatric patients with traumatic brain injury with
      intractable elevated intracranial pressure.
AB  - BACKGROUND: Care of pediatric traumatic brain injury (TBI) has placed emphasis on
      maximizing cerebral perfusion to prevent ischemia and reperfusion injury. A
      subset of patients with TBI will continue to have refractory intracranial
      pressure (ICP) elevation despite aggressive therapy including ventriculostomy,
      pentobarbital coma, hypertonic saline, and diuretics. Decompressive craniectomy
      (DC) is a controversial treatment of severe TBI. It is our hypothesis that DC can
      enhance survival and minimize secondary brain injury in this patient subset.
      METHODS: Patients younger than 20 years treated at a level I regional trauma
      center between November 2001 and November 2004, who met inclusion criteria for
      the Brain Trauma Foundation TBI-trac clinical database were included. All
      patients with a mechanism of injury consistent with TBI and Glasgow Coma Scale
      score of less than 9 for at least 6 hours after resuscitation and who did not die
      in the emergency department are entered into a clinical database. Patients who
      arrived at the study hospital more than 24 hours after injury are excluded.
      RESULTS: There were 30 patients with TBI identified. The mean Glasgow Coma Scale
      score at presentation was 8 with a range of 3 to 13. Six patients underwent DC
      for intractable elevated ICP. Of 6 patient's postoperative ICP, 5 were less than
      20 mm Hg. One patient required a return to the operating room where further
      debridement of brain was performed. All patients who received a DC survived and
      were discharged to a TBI rehabilitation facility. CONCLUSION: Although this is a
      small sample, DC should be considered in patients with TBI with refractory
      elevated ICP. Long-term follow-up of this patient population should consist of
      neuropsychiatric evaluation in conjunction with measurement of social function.

PMID- 16410114
TI  - The impact of obesity on severely injured children and adolescents.
AB  - PURPOSE/BACKGROUND: In conjunction with the obesity epidemic in adults, we are
      starting to see an increase of obesity in children and adolescents. Obesity has
      been identified as risk factor for poor outcomes in adult trauma patients, but
      has not been investigated adequately in younger patients. The purpose of this
      study was to investigate the impact of obesity on the outcomes of a severely
      injured population of children and adolescents. METHODS: Retrospective review of
      traumatized children (age 6-12) and adolescents (age 13-19) admitted to the
      intensive care unit (ICU) at an urban, level I trauma center from 1998 to 2003.
      The trauma registry and ICU database were used for data acquisition. Height and
      weight were recorded for each patient upon admission to the ICU and used to
      calculate body mass index (BMI). Patients were categorized as either lean (BMI
      <95th percentile for age) or obese (BMI > or =95th percentile for age). The two
      groups were compared regarding admission demographics, vital signs, mechanism of
      injury, patterns of injury, Injury Severity Score, and operations required.
      Outcomes evaluated were need for and length of mechanical ventilation,
      complications, length of hospital and ICU stay, and mortality. RESULTS: There
      were 316 pediatric and adolescent trauma patients (262 [83%] lean, mean BMI = 23
      kg/m2 and 54 [17%] obese, mean BMI = 33 kg/m2) admitted to the ICU. The lean and
      obese groups were similar regarding age, sex, mechanism of injury, admission
      vitals, injury severity, and operations required. Injury patterns were similar,
      except obese patients had less severe head injuries. Although there was no
      difference in mortality among obese (15%) and non-obese (9%) patients (P = .39),
      obese children did have more complications (41% vs 22%, P = .04). In addition,
      obese patients required longer ICU stays (8 +/- 9 vs 6 +/- 6 days, P = .05) after
      severe trauma. CONCLUSIONS: Despite similar admission characteristics and less
      severe head injuries, obese children and adolescents have more complications and
      require longer ICU stays than their lean counterparts.

PMID- 16410115
TI  - Outcomes and delivery of care in pediatric injury.
AB  - PURPOSE: To design effective pediatric trauma care delivery systems, it is
      important to correlate site of care with corresponding outcomes. Using a
      multistate administrative database, we describe recent patient allocation and
      outcomes in pediatric injury. METHODS: The 2000 Kids' Inpatient Database,
      containing 2,516,833 inpatient discharge records from 27 states, was filtered by
      E-code to yield pediatric injury cases. Injury Severity Scores (ISSs) were
      derived for each discharge using ICDMAP-90 (Tri-Analytics, Inc, Forest Hill, MD).
      After weighting to estimate national trends, cases were grouped by age (0-10, >10
      20 years), ISS (< or =15, >15), and National Association of Children's Hospitals
      and Related Institutions-designated site of care. Measured outcomes included
      mortality, length of stay, and total charges. Analysis was completed using
      Student's t test and chi2. RESULTS: Among 79,673 injury cases, mean age was 12.2
      +/- 6.2 years and ISS was 7.4 +/- 7.6. Eighty-nine percent of injured children
      received care outside of children's hospitals. In the subgroup of patients aged 0
      to 10 years with ISS of greater than 15, the mean ISS for adult hospitals and
      children's hospitals was not significantly different (18.9 +/- 9.1 vs. 19.4 +/-
      9.3, P = .08). However, in-hospital mortality, length of stay, and charges were
      all significantly higher in adult hospitals (P < .0001). CONCLUSIONS: Younger and
      more seriously injured children have improved outcomes in children's hospitals.
      Appropriate triage may improve outcomes in pediatric trauma.

PMID- 16410116
TI  - Effect of corticosteroid therapy on outcomes in biliary atresia after Kasai
      portoenterostomy.
AB  - PURPOSE: This study tests the hypothesis that steroid administration improves the
      outcome of biliary atresia (BA) by evaluating the efficacy of postoperative
      steroid use on surgical outcomes in infants with BA. METHODS: Steroid use and
      outcomes in patients with BA were retrospectively analyzed at a tertiary
      pediatric hospital. Institutional review board approval was obtained. RESULTS:
      Kasai portoenterostomy (PE) was performed in 43 patients with BA treated from
      1992 to 2004 (16 boys and 27 girls). Twenty-one PE patients received steroids and
      22 did not. Portoenterostomy was successful in 24 patients (55.8%) with
      consistent serum bilirubin less than 2 mg/dL. Sixteen (66%) received
      postoperative steroids. A normal postoperative bilirubin was achieved at 6 months
      in 16 (76%) of 21 patients with steroids compared with 8 (37%) of 22 in untreated
      controls (Fisher's Exact test, P = .01). Of the 43 patients, 19 (44%) required
      liver transplantation, including 7 (37%) of 19 with steroids vs 12 (63%) of 19
      without (P = .2). Twenty-eight infants developed cholangitis (fever with and
      without changes in hepatic function): 25 after PE and 3 after transplant. Of the
      25, 12 (48%) received steroids. Seven died (16%) (range, 7 months to 4 years): 2
      while awaiting transplantation (received steroids) and 5 after transplantation (1
      received steroids and 4 were untreated). Survival was 86% (18/21) in patients
      with steroids and 82% (18/22) in those without. Transplant survival (74%) was
      comparable to previously reported historical controls (82%). CONCLUSIONS: The
      Kasai PE continues to be the procedure of choice in infants with BA younger than
      3 months. A significantly improved clearance of postoperative jaundice and lower
      serum bilirubin levels were observed in patients receiving steroids. However,
      steroids had no effect on the incidence of cholangitis, need for liver
      transplantation, and overall survival. A prospective study with standardized dose
      and length of steroid administration and longer period of follow-up is necessary
      to more accurately assess the effectiveness of steroids after PE.

PMID- 16410117
TI  - Relief of intractable pruritus in Alagille syndrome by partial external biliary
      diversion.
AB  - BACKGROUND: Patients with Alagille syndrome (AGS) may develop pruritus, skin
      hypertrophy, and xanthomas because of chronic cholestasis and
      hypercholesterolemia. Partial external biliary diversion (PEBD) has been used
      successfully to treat chronic cholestasis in patients with progressive familial
      intrahepatic cholestasis (PFIC) and is a potentially useful treatment for
      patients with severe and intractable pruritus because of AGS. METHODS: Four
      children with chronic cholestasis and intractable pruritus were treated with
      PEBD, 1 by surgical cholecystostomy and 3 by cholecystojejunostomy. RESULTS:
      Three patients had a known diagnosis of AGS. The fourth was an 11-month-old
      infant boy with PFIC. The first patient, a 15-month-old boy with AGS, underwent
      surgical cholecystostomy, which has required frequent tube changes to maintain
      patency. Three patients underwent PEBD using a segment of jejunum as a conduit
      between the gallbladder and the skin, where bile is collected in a standard
      ostomy appliance. Mean follow-up is 15.5 months (range, 9-26 months). All
      patients experienced rapid and enduring relief of pruritus. Two adolescents with
      AGS had significant improvement of the hypertrophic skin of their hands. There
      was one significant complication: the infant with PFIC required reoperation for
      bleeding from the jejunal anastomosis 1 week after PEBD; he has subsequently done
      well. One adolescent girl with AGS initially had difficulty with her ostomy
      because of poor site placement and partial retraction, but nevertheless has
      managed quite well. The patient treated by cholecystostomy has had excellent
      relief of his pruritus and is being considered for conversion to
      cholecystojejunostomy. CONCLUSIONS: Chronic cholestasis caused by AGS can cause
      debilitating symptoms that are resistant to medical therapy. Partial external
      biliary diversion is a safe and technically straightforward operation that may be
      effective for the relief of intractable pruritus and other symptoms in patients
      with AGS.

PMID- 16410118
TI  - Effectiveness of Rex shunt in the treatment of portal hypertension.
AB  - BACKGROUND: Children with portal venous thrombosis often have severe symptoms
      secondary to portal hypertension including recurrent upper gastrointestinal (UGI)
      bleeds and hypersplenism. We report results of the use of the mesenterico-left
      portal bypass (Rex shunt) in 5 consecutive patients. METHODS: A retrospective
      chart review of all patients with portal venous thrombosis who underwent Rex
      shunt procedure was performed. Children were evaluated preoperatively with
      magnetic resonance angiogram, Doppler ultrasound, and mesenteric angiogram.
      Postoperative ultrasounds were performed in follow-up. RESULTS: All patients had
      evidence of portal hypertension and hypersplenism. The average age of the
      patients was 13.2 +/- 4.9 (7-19) years. The patient had an average of 2.6 +/- 1.7
      UGI bleeds requiring banding and 3.4 +/- 4.2 U of blood transfused before
      undergoing the shunt. The mean operative time was 383 +/- 46 minutes, and length
      of stay was 10.4 +/- 7.1 days. In follow-up of 18.8 +/- 5.2 months (11-24
      months), all but 1 patient had a patent shunt. One narrowed shunt was
      successfully dilated by percutaneous angioplasty. Thrombocytopenia improved
      significantly in patients with functioning shunts but did not correlate with a
      significant decrease in splenic size. CONCLUSIONS: The Rex shunt reestablishes
      normal hepatopedal portal flow, and in patients with functioning shunts, no
      recurrent UGI bleeds or transfusions were required or evidence of encephalopathy
      were noted.

PMID- 16410119
TI  - The Bianchi procedure: a 20-year single institution experience.
AB  - BACKGROUND/PURPOSE: The emergence of improved outcomes for small bowel (SB)
      transplantation has raised questions regarding the utility of autologous
      intestinal lengthening for patients with short bowel syndrome (SBS). Chronic
      immunosuppression, multiple hospitalizations, and posttransplant
      lymphoproliferative disease are significant adverse factors. The purpose of this
      study is to evaluate the 20-year single institution experience with the Bianchi
      procedure and analyze its role in the management of pediatric SBS. METHODS:
      Medical records for 19 consecutive patients who underwent the Bianchi procedure
      from 1984 to 2004 were reviewed. Patients were categorized into 3 groups: less
      than 5 years, 5 to 9.9 years, and 10 years or more after surgery. Various outcome
      variables were evaluated. Data are presented in tabular format as the number of
      patients (%) or average (range). RESULTS: Nineteen patients were included in the
      study. Of 16 patients weaned from total parenteral nutrition (TPN), 7 (44%)
      responded to Bianchi procedure alone and 9 patients (56%) required SB transplant
      at an average of 4.09 years (range, 0.7-13.64 years) post-Bianchi. Four patients
      (21%) died, 1 received SB transplant and died of unrelated causes, and 3 were
      still on TPN and had not received SB transplantation. CONCLUSION: The Bianchi
      procedure facilitated weaning from TPN and eliminated the need for supplemental
      nutrition in select patients. Although the role of surgery is primarily
      adjunctive in the treatment of SBS, it offers therapeutic benefit in decreasing
      parenteral nutrition requirements and promoting intestinal adaptation. In
      particular, the Bianchi procedure has significant potential to improve the
      prognosis of pediatric patients with SBS.

PMID- 16410120
TI  - Laparoscopic Nissen fundoplication without division of short gastric vessels in
      children.
AB  - PURPOSE: It has been suggested that routine division of short gastric vessels
      (SGVs) results in a more "floppy" Nissen fundoplication leading to improved
      outcomes, that is, less dysphagia and lower incidences of recurrent
      gastroesophageal reflux disease (GERD). The aim of this retrospective study was
      to assess whether laparoscopic Nissen fundoplication without division of SGVs
      (Rossetti modification) (laparoscopic Nissen-Rossetti fundoplication [LNRF]) is
      associated with acceptable clinical outcome in children. METHOD: The charts of
      368 children who underwent LNRF between January 1996 and September 2004 by 1
      primary surgeon were retrospectively reviewed. Children were divided into 2
      groups: LNRF + gastrostomy (A) and LNRF alone (B). Mean follow-up period of all
      groups was 4.2 years. RESULTS: Laparoscopic Nissen-Rossetti fundoplication was
      completed in 99% (365/368). Mean operating time for group A was 74 minutes and 61
      minutes for group B. None in group A required postoperative esophageal
      dilatation, and 9 in group B (22.5%) required 12 dilatations; 3.6% developed
      recurrent GERD, 3.7% in group A and 2.5% in group B. CONCLUSION: Laparoscopic
      Nissen-Rossetti fundoplication can be performed with acceptable long-term outcome
      in children, especially in the majority also requiring chronic gastrostomy
      access. Short-term, reversible dysphagia may be seen in a small percentage of
      children having fundoplication alone.

PMID- 16410121
TI  - New clinical and therapeutic perspectives in Currarino syndrome (study of 29
      cases).
AB  - PURPOSE: The aim of the study was to clearly define the anomalies that compose
      the Currarino syndrome (CS). We highlight the frequency of associated
      malformations of the spinal cord and the possibility of a communication between
      the presacral tumor and the spinal canal, leading to neurological complications.
      METHODS: We studied 29 patients with CS, including 12 familial cases;
      histological examination of the presacral tumor was performed, and cytogenetic
      and molecular biology studies of the HLXB9 locus were carried out. RESULTS: All
      except 2 patients had a sacral malformation; 23 had an anorectal anomaly and 8
      had isolated chronic intestinal pseudo-obstruction. There were 20 presacral
      tumors, one of which was malignant. There was a communication between the
      presacral tumor and the spinal canal in 12 cases, and tethering of the spinal
      cord in 17 cases. Twenty-five patients underwent surgery with a single-stage
      operation for 7, on both the intestinal and the presacral malformations, and,
      when required, the spinal cord anomalies. Twelve patients harbored a heterozygous
      point mutation of the coding sequence of HLXB9 gene. CONCLUSION: By accurate
      evaluation of the 4 main features in the CS, the correct surgical management,
      including neurosurgery, can be performed in a 1-stage approach.

PMID- 16410122
TI  - The fibroblast growth factor pathway serves a regulatory role in proliferation
      and apoptosis in the pathogenesis of intestinal atresia.
AB  - BACKGROUND/PURPOSE: Intestinal atresia occurs in 1:5000 live births and is a
      neonatal challenge. Fibroblast growth factor receptor 2b (Fgfr2b) is a critical
      developmental regulator of proliferation and apoptosis in multiple organ systems
      including the gastrointestinal tract (GIT). Fgfr2b invalidation results in an
      autosomal recessive intestinal atresia phenotype. This study evaluates the role
      of Fgfr2b signaling in regulating proliferation and apoptosis in the pathogenesis
      of intestinal atresia. METHODS: Wild-type and Fgfr2b-/- embryos were harvested
      from timed pregnant mice. The GIT was harvested using standard techniques.
      Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) was used to
      evaluate apoptosis and bromodeoxyuridine to assess proliferation by standard
      protocols. Photomicrographs were compared (Institutional Animal Care and Use
      Committee-approved protocol 32-02). RESULTS: Wild-type and mutant GIT demonstrate
      that deletion of the Fgfr2b gene results in inhibition of epithelial
      proliferation and increased apoptosis. Inhibited proliferation and increased
      apoptosis are specific to those tissues of normal Fgfr2b expression,
      corresponding to the site of intestinal atresia. CONCLUSIONS: The absence of
      embryonic GIT Fgfr2b expression results in decreased proliferation and increased
      apoptosis resulting in GIT atresia. The regulation of proliferation and apoptosis
      in intestinal cells as a genetically based cause of intestinal atresia represents
      a novel consideration in the pathogenesis of intestinal atresia.

PMID- 16410123
TI  - One-year outcomes of Roux-en-Y gastric bypass for morbidly obese adolescents: a
      multicenter study from the Pediatric Bariatric Study Group.
AB  - BACKGROUND/PURPOSE: Little is known about the metabolic outcomes of adolescent
      bariatric surgery. We report changes in weight, metabolic profile, and types of
      complications seen in a multicenter cohort. METHODS: One-year outcomes were
      included. For weight loss comparisons, a nonsurgical cohort (n = 12) was used.
      The primary outcome was weight change (n = 30) and secondary outcomes were
      metabolic variables (n = 24) and complications (n = 36). Data were analyzed using
      signed rank or paired t tests. RESULTS: Mean body mass index fell 37% (from 56.5
      preoperatively to 35.8 kg/m2; P < .001) in surgical patients and 3% (from 47.2 to
      46 kg/m2; P = NS) in nonsurgical patients. Surgical patients showed significant
      improvements in triglycerides (-65 mg/dL), total cholesterol (-28 mg/dL), fasting
      blood glucose (-12 mg/dL), and fasting insulin (-21 microM/mL]). Improvement in
      high-density lipoprotein cholesterol (-3.9 mg/dL) and low-density lipoprotein
      cholesterol (-8.8 mg/dL) was not statistically significant. Sixty-one percent of
      surgical patients had no complications. Of 15 patients with complications, 9 had
      minor complications with no long-term sequelae, 4 had at least 1 moderate
      complication with sequelae for at least 1 month and 2 had at least 1 severe
      medical complication with long-term consequences (including beriberi and death).
      There were no perioperative deaths or other severe surgical complications in this
      series. CONCLUSIONS: Postoperatively, adolescents lose significant weight and
      realize major metabolic improvements. The complication profile compares favorably
      to severely obese (body mass index >40 kg/m2) adults; however, small sample size
      precludes calculation of complication rates. Although there are considerable
      risks of bariatric surgery, early experience suggests that risks are offset by
      health benefits.

PMID- 16410124
TI  - Heparin-binding epidermal growth factor-like growth factor decreases the
      incidence of necrotizing enterocolitis in neonatal rats.
AB  - PURPOSE: We have previously demonstrated that heparin-binding epidermal growth
      factor-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent.
      The aim of this study was to determine the effect of enterally administered HB
      EGF on the incidence of necrotizing enterocolitis (NEC) in neonatal rats.
      METHODS: Necrotizing enterocolitis was induced in neonatal rats delivered by C
      section on day 21 of gestation by exposure to repeated cycles of hypoxia and
      hypothermia plus administration of hypertonic formula feeding (HHHTF) plus
      enteral administration of lipopolysaccharide (LPS) (2 mg/kg). Neonatal rats were
      randomly assigned to breast-feeding, hypertonic formula feeding, HHHTF + LPS, and
      HHHTF + LPS with HB-EGF (600 mug/kg) supplementation in the formula. Animals were
      monitored until 96 hours of life and assessed for death, histological NEC, and
      intestinal mucosal permeability. RESULTS: The incidence of NEC in the HHHTF group
      was higher than that in the breast-feeding or hypertonic formula feeding groups.
      With administration of HB-EGF, the incidence and severity of NEC were
      significantly decreased. Administration of HB-EGF also increased rat pup survival
      rate and extended survival time. In addition, treatment with HB-EGF significantly
      decreased intestinal permeability to fluorescein isothiocyanate-dextran.
      CONCLUSIONS: We conclude that HB-EGF reduces the incidence and severity of NEC in
      a neonatal rat model, with simultaneous preservation of gut barrier integrity.
      These results support our contention that HB-EGF administration may represent a
      useful therapeutic and prophylactic therapy for the treatment of NEC.

PMID- 16410125
TI  - Hepatocyte growth factor increases glucagon immunoreactivity in jejunal cells
      during intestinal adaptation.
AB  - BACKGROUND: The administration of hepatocyte growth factor (HGF) during
      intestinal adaptation is known to enhance intestinal adaptation. Glucagon has
      also been implicated as a potential mediator of intestinal adaptation. Previous
      studies have shown that HGF and glucagon synergistically increase the
      proliferation of hepatocytes. HGF has also been shown to be preferentially
      expressed within the glucagon-positive cells of the pancreas, possibly indicating
      a paracrine or endocrine effect of HGF on glucagon. This study was designed to
      determine if HGF stimulation in the small intestine during intestinal adaptation
      influenced mucosal glucagon expression. METHODS: Adult male Sprague-Dawley rats
      were randomized to either a 70% massive small bowel resection group (MSBR) or an
      HGF-treated MSBR group (MSBR-HGF). Seven days after surgery, HGF was administered
      intravenously at 150 mug/kg per day for 14 days. At day 21, the ileal and jejunal
      mucosa was harvested. The RAE 230A GeneChip (Affymetrix, Santa Clara, Calif) and
      MAS5 software were used to determine alterations in gene expression in the small
      intestine mucosa. Immunofluorescent staining of the ileal and jejunal mucosa
      using an antiglucagon antibody was performed and evaluated qualitatively.
      RESULTS: The MSBR-HGF group had significantly greater protein and DNA content (P
      < .05) than the MSBR group. Glucagon gene expression in the MSBR-HGF group was
      decreased compared with the MSBR group, and immunohistostaining for glucagon in
      the ileum revealed no difference in intensity between the 2 groups. However, the
      jejunal MSBR-HGF group demonstrated significantly greater glucagon
      immunoreactivity than the jejunal MSBR group. CONCLUSION: Our data suggest that
      the HGF-induced increase in glucagon availability is disassociated from glucagon
      gene up-regulation. Thus, HGF may not only enhance intestinal adaptation
      directly, but also indirectly by increasing the "local" availability of other
      growth factors in the absence of their gene up-regulation.

PMID- 16410126
TI  - Evaluation of a Bayesian decision network for diagnosing pyloric stenosis.
AB  - PURPOSE: Most infants undergoing an ultrasound to rule out pyloric stenosis will
      have a negative study, suggesting the low accuracy of clinical assessment. The
      purpose of this study was to evaluate the feasibility of using a Bayesian network
      to improve the accuracy of diagnosing pyloric stenosis. METHODS: Records of 118
      infants undergoing an ultrasound to rule out pyloric stenosis were reviewed. Data
      from 88 (75%) infants were used to train a Bayesian decision network that
      predicted the probability of pyloric stenosis using risk factors, signs, and
      symptoms of the disease. The emergency department records of the remaining 28
      (25%) infants were used to test the network. Two groups of pediatric surgeons and
      pediatric emergency medicine physicians were asked to predict the probability of
      pyloric stenosis in the testing set: (1) physicians using the network and (2)
      physicians using only emergency department records. Accuracy was evaluated using
      area under the ROC curve (discrimination) and Hosmer-Lemeshow (H-L) c-statistic
      (calibration). RESULTS: Physicians using the Bayesian decision network better
      predicted the probability of pyloric stenosis among infants in the testing set
      than those not using the network (ROC 0.973 vs 0.882; H-L c-statistic 3.9 [P >
      .05] vs 24.3 [P < .05]). Physicians using the network would have ordered 22%
      fewer ultrasounds and missed no cases of pyloric stenosis. CONCLUSIONS: The use
      of a Bayesian decision network may improve the accuracy of physicians diagnosing
      infants with possible pyloric stenosis. Use of this decision tool may safely
      reduce the need for imaging among infants with suspected pyloric stenosis.

PMID- 16410127
TI  - The value of surgery in directing therapy for patients with Wilms' tumor with
      pulmonary disease. A report from the National Wilms' Tumor Study Group (National
      Wilms' Tumor Study 5).
AB  - BACKGROUND/PURPOSE: Computed tomography (CT) of the chest with its increased
      sensitivity frequently identifies lesions not visible on chest radiograph.
      Treatment of such lesions is controversial. A recent review suggests that
      patients with Wilms' tumor with pulmonary lesions detected only by CT, who were
      treated with dactinomycin and vincristine, have an inferior outcome compared with
      those who also received pulmonary radiation therapy (RT) and doxorubicin. It is
      important to determine if these small lesions seen only on CT represent
      metastatic disease and whether patients with these lesions require RT and/or
      doxorubicin for optimal outcome. METHODS: Patients with Wilms' tumor with lung
      metastasis, registered on National Wilms' Tumor Study 5, were reviewed, and those
      with CT-only lesions who had a radiology and surgical checklist submitted were
      identified. The treatment regimens of these patients and the histological
      findings of the pulmonary lesions are presented. We analyzed the pathological
      findings by whether the patients had single or multiple lesions. RESULTS: Of 2498
      patients registered on National Wilms' Tumor Study 5, 252 had pulmonary
      metastases. Of these patients, 129 (5.2%) had CT-only lesions (<1 cm). Forty-two
      of these patients (20 boys and 22 girls) underwent lung biopsy at the discretion
      of the attending physicians. The local tumor stages in these patients were stage
      I (7%), II (34%), and III (59%). The treatment stages in these patients were
      stage I (n = 3, 2 drugs), II (n = 3, 2 drugs), III (n = 12, 3 drugs); and IV (n =
      24, 3 drugs + RT). There were 16 patients with isolated lung lesions and 26 with
      multiple lesions, average size 5.8 +/- 0.5 mm. Of 16 isolated lesions, 13
      patients (82%) and 69% (18/26) with multiple lesions had tumor on biopsy. Of the
      24 who received RT, 8 had a negative biopsy and, thus, may not have needed the
      RT. Five of 6 treated with just 2 drugs may have been undertreated. Nine of 12
      treated with 3 drugs had tumor on biopsy. CONCLUSIONS: Computed tomography-only
      pulmonary lesions are not invariably tumor, demonstrating the need for
      histopathological confirmation. Biopsy remains critical until radiographic
      techniques allow differentiation between benign and malignant lesions to
      optimally direct therapy.

PMID- 16410128
TI  - Primary hepatic metastases in nephroblastoma--a report of the SIOP/GPOH Study.
AB  - PURPOSE: Remarkable progress could be achieved in the treatment of nephroblastoma
      within the last decades. In all children with Wilms' tumor, 5-year overall
      survival rate reaches more than 90% in the SIOP/GPOH Study Group. Despite this
      fact, there is a small group of patients who have tumor lesions in the liver
      primarily representing a challenge in treatment. Data of this group are analyzed.
      METHODS: To define survival and success of treatment in this group of patients,
      we reviewed the records of 29 of 1365 patients enrolled in the SIOP 93-01/GPOH
      Study and the SIOP 2001/GPOH Study between April 1, 1994, and September 30, 2004.
      RESULTS: Median age at diagnosis was 10.61 years (range, 0.19-34.16 years). All
      patients but two underwent nephrectomy. Liver metastases were operated in 11
      children at time of nephrectomy, in 4 patients secondarily, whereas in 11
      patients, liver lesions were treated alone with chemotherapy and radiotherapy,
      respectively. In 3 children, no treatment could be initiated. Sixteen patients
      received radiotherapy additionally. Median follow-up was 64 months (range, 3-157
      months). Eleven patients died in the course at a median of 13.07 months (range,
      0.25-42 months) after initial diagnosis. These included 7 patients who never had
      surgery for their liver lesions and 4 patients who had incomplete and/or atypical
      resections of their metastatic liver lesions. All patients who underwent complete
      resection of hepatic metastases (n = 9) survived. Eight children survived with a
      nonsurgical treatment. Overall survival was below 60% in the whole group up to
      now. CONCLUSIONS: Liver metastases are much less frequent than metastases to
      other sites. Our report suggests that Wilms' tumor complicated by metastases of
      the liver primarily has a less favorable outcome. Chemotherapy and radiotherapy
      play an important role in treatment. Radical surgery for nephrectomy as well as
      surgery of liver lesions cannot be overemphasized to prevent local and distant
      recurrence.

PMID- 16410129
TI  - Study of the factors associated with recurrence in children with sacrococcygeal
      teratoma.
AB  - PURPOSE: The aim of this study was to explore effects of (1) histological
      involvement of resection margins with microscopic residue, (2) incomplete removal
      of coccyx, and (3) tumor spillage on recurrence and on survival in children
      operated upon for sacrococcygeal teratoma (SCT). METHODS: Retrospective review of
      70 patients treated between 1960 and 2003. RESULTS: Fifty-four girls and 16 boys
      presented with SCT diagnosed prenatally (12), at birth (37), or later (21).
      Thirty-six percent of tumors were Altman type I, 27% type II, 18% type III, and
      18% type IV. Histologically, mature teratoma was observed in 48 patients,
      immature teratoma in 11, yolk sac tumor (YST) in 9, embryonal carcinoma in one,
      and mixed tumor in one. Eighty-four percent of patients solely underwent surgical
      extirpation. Six (8.5%) patients died. However, mortality for the group of 42
      patients treated during the past 15 years was as low as 2.5%. Tumor recurrence
      was observed in 5 patients, 2 of whom died. Of 3 patients with initially mature
      teratoma, 1 showed local immature recurrence and 2 malignant recurrences. One of
      the latter died. Of 2 patients with initially immature teratoma grade I, one
      relapsed with a benign lesion and one with YST leading to death. Possible
      eliciting factors had been demonstrated in 3 patients. Histological analysis of
      resection margins showed tumoral involvement in 11 patients (and also in one
      patient after resection of a recurrent tumor). Only one of those with YST focus
      in the resection margin showed recurrence. Intraoperative tumor spillage
      presented in 2 patients, who both died of metastatic disease. Spillage of tumoral
      cyst fluid occurred in 6, none developed recurrence. One of 5 patients whose
      coccyx had not been removed died of metastatic disease. One with immature
      teratoma developed a benign recurrent tumor. The other 3 showed no recurrence.
      CONCLUSIONS: Microscopic involvement of the resection margins of mature or
      immature SCT is rarely associated with recurrence, provided there are no YST foci
      in the resection margins. A conservative attitude then appears to be justified.
      Spillage of cyst fluid was never associated with recurrence, unlike spillage of
      tumor and absence of removal of coccyx.

PMID- 16410130
TI  - Liver transplantation for childhood hepatic malignancy: a review of the United
      Network for Organ Sharing (UNOS) database.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is the only treatment option
      for unresectable hepatoblastoma (HB) and hepatocellular carcinoma (HCC) in
      children. Aggregated outcomes of OLT for these hepatic malignancies have not been
      evaluated in the United Network for Organ Sharing national database. PURPOSE: The
      purpose of this study was to evaluate graft and patient survival in pediatric OLT
      recipients with HB and HCC. METHODS: Data from the United Network for Organ
      Sharing Standard Transplant and Research Files were analyzed and included
      pediatric (<18 years) OLT recipients with HB or HCC from 1987 to 2004. The
      effects of diagnosis on pretransplant variables were evaluated using analysis of
      variance methods or chi2 tests, as appropriate. Actuarial survival and effect of
      diagnosis on survival were determined using Kaplan-Meier methods and log-rank
      tests. RESULTS: Since 1987, 152 OLTs have been performed in 135 pediatric
      patients for HB and 43 OLTs in 41 pediatric patients for HCC. Respective 1-, 5-,
      and 10-year patient survival after OLT was 79%, 69%, and 66% for HB and 86%, 63%,
      and 58% for HCC (P = .73). The primary cause of death for both groups was
      metastatic or recurrent disease, accounting for 54% of deaths in the HB group and
      86% in the HCC group (P = .338). Patients with hepatoblastoma were younger (mean
      age, 2.9 +/- 2.5 vs 10.4 +/- 4.8 years for the HCC group; P < .001) and more
      likely to receive a living donor organ (16% vs 4%, P = .03). A greater proportion
      of the patients with HB had previous abdominal surgery than patients with HCC
      (63% HB vs 37% HCC, P = .04). Pretransplant medical condition and transplant era
      were associated with graft and patient survival on univariate and multivariate
      analysis (all P < .05). CONCLUSIONS: Orthotopic liver transplantation remains a
      viable option for pediatric patients with unresectable primary hepatic
      malignancies and results in good long-term survival. Pretransplant medical
      condition is an important predictor of outcome. Thus, in conjunction with better
      chemotherapy regimens, earlier evaluation for OLT in patients with unresectable
      HB and HCC may result in yet further improved long-term survival.

PMID- 16410131
TI  - Clinical presentation, treatment, and outcome of alveolar soft part sarcoma in
      children, adolescents, and young adults.
AB  - PURPOSE: Alveolar soft part sarcoma is a rare soft tissue neoplasm that can
      affect children and adolescents. There are few reported series of these patients
      in the literature. To define the clinical presentation, treatment, and outcome of
      young people with this rare sarcoma, we reviewed our clinical experience.
      METHODS: After institutional review board approval, we examined the records of
      all patients younger than 25 years old who received treatment at our institution
      for alveolar soft part sarcoma in the past 30 years. Demographics, tumor sizes,
      sites and extent of disease, treatments used, progression-free survival, and
      overall follow-up were evaluated. RESULTS: Each of the 20 patients presented with
      a mass. Primary disease sites were thigh (n = 8), trunk (n = 6), retroperitoneum
      (n = 2), and scalp, neck, forearm, and calf (n = 1 each). Metastatic sites
      included lymph nodes, lung, and brain. Four patients presented to us with
      incomplete excision of the primary, and 1 had undergone embolization of what was
      thought to be a vascular malformation. Although wide local excision provided the
      best chance for a patient to remain free of disease, 14 (70%) of 20 patients
      exhibited metastases either at presentation or later. Thirty-one metastasectomies
      were performed. Chemotherapy was used in 11 patients; radiation was used in 8.
      Median overall follow-up was 36 months; median progression-free follow-up was
      12.5 months. Younger patients tended to have Intergroup Rhabdomyosarcoma Study
      group I disease. Tumors smaller than 5 cm were associated with longer progression
      free survival. CONCLUSIONS: Achievement of complete microscopic resection is
      critical in localized alveolar soft part sarcoma, but incomplete excision and
      misdiagnosis are often encountered. Despite the occurrence of metastases in 70%
      of patients, 5-year overall survival was 83%. We found an association between
      smaller tumor size and longer time to progression. We were not able to
      demonstrate any benefit from chemotherapy or radiation. Metastasectomies have
      been performed in multiple long-term survivors.

PMID- 16410132
TI  - Long-term survival after aggressive resection of pulmonary metastases among
      children and adolescents with osteosarcoma.
AB  - PURPOSE: Although survival without resection of pulmonary metastases from
      osteosarcoma is unlikely, not all surgeons agree on an aggressive surgical
      approach. We have taken an approach to attempt surgical resection if at all
      feasible regardless of number of metastases and disease-free interval (DFI). This
      study presents information on long-term follow-up after this aggressive approach
      to resection. METHODS: A single-institution retrospective cohort study of
      osteosarcoma patients younger than 21 years with pulmonary metastases, limited to
      the contemporary chemotherapeutic period (1980-2000), was conducted. RESULTS: In
      137 patients, synchronous (23.4%) or metachronous (76.6%) pulmonary nodules were
      identified. The median follow-up was 2.0 years (5 days to 20.1 years) for all
      patients. Overall survival among patients who had pulmonary nodules was 40.2% and
      22.6% at 3 and 5 years, respectively. Ninety-nine patients underwent attempted
      pulmonary metastasectomy (mean survival, 33.6 months; 95% confidence interval,
      25.1-42.1) and 38 patients did not (mean survival, 10.1 months; 95% confidence
      interval, 6.5-13.6; P < .001, t test). Characteristics that were associated with
      an increased likelihood of 5-year overall survival after pulmonary resection were
      primary tumor necrosis greater than 98% after neoadjuvant chemotherapy (P < .05)
      and DFI before developing lung metastases more than 1 year (P < .001). No
      statistically significant difference in overall survival or disease-free survival
      was found based on the number of pulmonary metastases resected. Characteristics
      including primary tumor size, site, or extension; chemotherapy; early vs late
      metastases; unilateral vs bilateral metastases; and resection margins did not
      significantly affect survival. CONCLUSIONS: Most patient and tumor
      characteristics commonly used by surgeons to determine utility of resection of
      pulmonary metastases among patients with osteosarcoma are not associated with
      outcome. Biology of the particular tumor (response to preoperative chemotherapy,
      measured by tumor necrosis percentage, and DFI), as opposed to tumor burden,
      appears to influence survival more significantly. We would advocate considering
      repeat pulmonary resection for patients with recurrent metastases from
      osteosarcoma.

PMID- 16410133
TI  - Computed tomographic scan of the chest underestimates the number of metastatic
      lesions in osteosarcoma.
AB  - PURPOSE: Survival in osteosarcoma correlates with complete resection of primary
      and metastatic disease. The feasibility of complete pulmonary metastasectomy
      using thoracoscopy has been raised. Because palpation is not possible, minimally
      invasive techniques require preoperative radiological enumeration and
      localization of metastases not presenting at the lung surface. We hypothesized
      that computed tomographic (CT) scanning underestimated the number of pulmonary
      metastases in these patients. METHODS: Institutional review board approval was
      obtained. We determined the association between the number of lesions identified
      by CT scanning and the number of metastases found at thoracotomies for metastatic
      osteosarcoma from May 1996 to October 2004. Correlations between CT findings and
      pathology results were computed using the Kendall tau-b correlation coefficient.
      Depth, in millimeters, from the pleural surface was measured for those lesions
      seen on CT scan. RESULTS: We analyzed 54 consecutive thoracotomies performed in
      28 patients for whom complete imaging was available. Computed tomographic
      scanning was performed a median of 20 days before thoracotomy (range, 1-85 days).
      Correlation between the number of lesions identified by CT and the number of
      metastases resected at surgery was poor, with a Kendall tau-b correlation
      coefficient of 0.45 (P < .001). In 19 (35%) of 54 thoracotomies, CT scanning
      underestimated the number of pathologically proven, viable and nonviable
      metastases found by the surgeon. Accounting for viable metastases only,
      correlation between the number of lesions identified by CT and the number of
      metastases resected at surgery was 0.50 (P < .001), and CT scanning
      underestimated the number of viable metastases present in 14 (26%) of 54
      thoracotomies. Many lesions (32%) were pleural-based, but nearly half (47%) were
      5 mm or deeper from the pleural surface of the lung. CONCLUSIONS: Even in the era
      of modern CT scanning, only a very rough correlation exists between CT findings
      and the number of lesions identified at thoracotomy. In more than one third of
      thoracotomies in our series, metastases would have been missed by any tactic
      besides manual palpation of the lung during open thoracotomy. Minimal access
      procedures should not be the approach of choice if the goal is resection of all
      pulmonary metastases in osteosarcoma.

PMID- 16410134
TI  - c-Myc inhibition negatively impacts lymphoma growth.
AB  - BACKGROUND: Proto-oncogene c-Myc dysregulation is commonly found in aggressive
      tumors. Dysregulation is central to lymphomagenesis in Burkitt lymphoma and other
      non-Hodgkin's lymphomas. This suggests targeting c-Myc as a treatment for myc
      associated malignancies. METHODS: Microarrays showed c-Myc dysregulation in a B
      lymphoblastoid line, TIB-215. This was confirmed by real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR) and extended to 3 additional
      Burkitt lymphoma lines. Growth effects of a c-Myc inhibitor, compound 10058-F4,
      were determined in these 4 lines using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide analyses and direct cell counts. Drug effects on c
      Myc gene expression levels were measured using minor groove binding-TaqMan real
      time reverse transcriptase-polymerase chain reaction. Drug specificity was
      analyzed in rat c-Myc knockout (-/-) and Myc-transfected cells. RESULTS: c-Myc
      dysregulation was shown to be cell-cycle independent without rapid decay of c-Myc
      mRNA levels in all 4 lines. Using a c-Myc inhibitor, we found that growth
      inhibition was time- and dose-dependent. This inhibition caused unexpected
      downregulation (> or =65%) of c-Myc mRNAs. CONCLUSIONS: The inhibition of c-Myc
      decreased growth in aggressive lymphoma cells. This mechanism included c-Myc mRNA
      downregulation and dissociation of c-Myc/Max protein heterodimer. These results
      support targeting c-Myc in tumors with high morbidity and mortality.

PMID- 16410135
TI  - Vacuum-assisted closure: a new method for treating patients with giant
      omphalocele.
AB  - INTRODUCTION: Closure of giant omphalocele can present a surgical challenge.
      Neither silo, skin flap, nor primary closure has been successful in treating all
      patients. We present a novel application of the vacuum-assisted closure (VAC)
      device, which allows for improved results in these difficult cases. METHODS: The
      VAC device (KCI, San Antonio, Tex) consisted of a sponge applied directly to the
      bowel and liver, covered with impermeable transparent dressing, and attached to a
      low negative pressure system. The sponge was changed every 3 to 5 days under
      local sedation. PATIENTS: All 3 patients had giant omphaloceles. The first
      infant, a 34 week gestational age (WGA) male, was initially treated with silo
      reduction, which disrupted after 21 days. The large mass of bowel and liver made
      primary closure impossible. The VAC was applied for 45 days. The viscera was
      easily reduced and subsequently covered with acellular dermal matrix (AlloDerm).
      The VAC was reapplied, and the small remaining defect was skin-grafted. The
      second male infant was a 34 WGA male infant who became septic after failure of
      prosthetic mesh closure. The VAC was applied for 22 days after removal of the
      mesh. The infection resolved, and the defect size was reduced, allowing for skin
      flap closure. Mesh infection and development of an enterocutaneous fistula in the
      last patient, a 37 WGA female child, were treated by mesh removal and application
      of the VAC for 36 days. The VAC allowed for control of the fistula output and
      development of a healthy granulation bed. RESULTS: Vacuum-assisted closure was
      associated with (1) rapid shrinkage and reduction of the viscera (22-45 days);
      (2) cleansing of the wound; (3) excellent granulation; (4) maintenance of a
      sterile environment; and (5) ease of use, with changes possible at the bedside.
      CONCLUSION: The VAC device should be considered a safe and effective alternative
      in treating complicated cases of giant omphalocele until a more definitive
      closure method can be used.

PMID- 16410136
TI  - The use of human acellular dermis in the operative management of giant
      omphalocele.
AB  - PURPOSE: The management of giant omphalocele presents a major challenge to
      pediatric surgeons. Current treatment modalities often result in wound infection,
      fascial separation, and abdominal domain loss. Human acellular dermis (AlloDerm),
      as a primary abdominal fascial substitute, may prevent these complications. We
      present our experience with its application in neonates with giant omphalocele.
      METHODS: Charts of patients with giant omphalocele from January 2003 to September
      2004 were reviewed and data collected regarding wound healing, rate of infection,
      ventilatory support, and outcome. RESULTS: Three neonates underwent abdominal
      wall closure with AlloDerm (gestational ages: 38, 37, and 28 weeks; birthweights
      2880, 2640, and 1160 g, respectively). All had cardiac anomalies; 1 required
      cardiac surgery and 1 was ventilator-dependent, secondary to pulmonary
      hypoplasia. Omphalocele repair was performed on day-of-life 9, 2, and 87. No
      fascial dehiscence or infection was encountered. Neovascularization was noted by
      day 7. Two died of cardiopulmonary disease (6 months and 1 year). The third
      exhibited normal growth and development without complication. CONCLUSIONS:
      AlloDerm provides visceral coverage without compromising cardiopulmonary
      function, diminishing abdominal domain, or requiring multiple operations,
      allowing prompt treatment of associated anomalies. AlloDerm represents an
      exciting alternative in the treatment of giant omphalocele. Further study is
      required to determine long-term benefits.

PMID- 16410137
TI  - Prognostic factors in the surgical treatment of congenital tracheal stenosis: a
      multicenter analysis of the literature.
AB  - BACKGROUND: Congenital tracheal stenosis (CTS) often requires urgent surgical
      intervention. We evaluated prognostic factors to determine the risks of surgical
      interventions by conducting a retrospective review of recent case series.
      METHODS: Cases of CTS between 2002 and 2004 from our institution and recently
      published series that provided primary data on the demographics, complications,
      and outcomes of patients with CTS were analyzed. Univariate, model fit, and
      multivariate logistic regression analyses were performed using the SAS
      Statistical Program. RESULTS: There were 68 patients who were treated (cartilage
      patch tracheoplasty, n = 31; slide tracheoplasty, n = 37), with 19 deaths
      (overall mortality = 28%). A total of 10 patients who underwent cartilage patch
      tracheoplasty died (32% mortality), whereas only 9 patients died following slide
      tracheoplasty (24% mortality). A total of 8 of 11 patients who were repaired at
      the age of 1 month or younger died (73% mortality), whereas only 11 of 57
      patients who were repaired at an age older than 1 month died (19% mortality) (P =
      .04). A total of 10 of 19 patients with CTS who had comorbid intracardiac
      anomalies died following CTS repair (53% mortality), whereas only 9 of 49
      patients with CTS who did not have intracardiac anomalies died (18% mortality) (P
      = .02). CONCLUSIONS: This is the first report on the prognostic factors
      determining surgical outcomes for CTS. The highest mortality rate was observed in
      CTS patients younger than 1 month and in those with intracardiac anomalies.
      Congenital tracheal stenosis repairs in these patient subgroups should be
      considered with caution.

PMID- 16410138
TI  - Aortoiliac reconstruction in infants and toddlers: replacement with
      decellularized branched pulmonary artery allograft.
AB  - BACKGROUND: Aortic reconstruction in infants and small children has been reported
      with Dacron or polytef prosthetic material, hypogastric artery autograft, and
      saphenous vein autograft. In children, synthetic grafts are limited by a concern
      for late infection and a lack of potential growth. Available autogenous vessels
      have a limited length and diameter. Conventional allografts have not been
      durable. When the entire infrarenal aorta and aortoiliac bifurcation must be
      replaced, none of the historic options are optimal. METHODS: We report 2 cases of
      infrarenal aorta and aortoiliac bifurcation reconstruction using a new generation
      of cryopreserved allograft now decellularized for decreased immunogenicity. The
      branched pulmonary artery allograft is particularly attractive for reconstruction
      of the aortic bifurcation. RESULTS: The postoperative course in both cases was
      uncomplicated. Follow-up with serial abdominal duplex ultrasound has shown no
      evidence of graft stenosis or calcification at 29 and 32 months, respectively.
      CONCLUSIONS: The use of commercially available, decellularized, and antigen
      reduced allograft offers a nonsynthetic option for replacement of the pediatric
      abdominal aorta. We chose this novel approach in hopes of reducing the lifetime
      risk for graft infection and maintaining the potential for graft ingrowth by the
      child.

PMID- 16410139
TI  - Severe pulmonary hypoplasia associated with giant cervical teratomas.
AB  - BACKGROUND: The use of the ex utero intrapartum treatment (EXIT) procedure has
      salvaged many fetuses with giant neck masses. Despite an adequate airway, a
      subset of these patients die from an inability to achieve adequate gas exchange.
      METHODS: We reviewed our experience with the EXIT procedure from 1996 to 2004.
      The EXIT was used to deliver 23 fetuses with giant neck masses. RESULTS: Three
      fetuses with giant cervical teratomas died of severe pulmonary hypoplasia. On
      postmortem, these patients had severe airway distortion by the mass. The carina
      was retracted superiorly to the first or second rib resulting in compression of
      the lungs in the apices of the chest and pulmonary hypoplasia. Hypoplasia was
      reflected in the lung weights of 24 vs 38 g and 17 vs 34 g for age-matched normal
      lung. CONCLUSIONS: Unsuspected obstructive fetal neck masses can be fatal because
      of an inability to secure an airway. Prenatal ultrasonography can identify
      fetuses at risk, allowing the fetus to be salvaged using the EXIT procedure.
      Despite obtaining airway control, a subset of these patients will die because of
      pulmonary hypoplasia. When counseling patients with large cervical masses it is
      important to discuss potential pulmonary hypoplasia in these patients.

PMID- 16410140
TI  - Relative value units correlate with pediatric surgeons' operating time: when
      perceived myth becomes reality.
AB  - PURPOSE: In 1992, the Congress implemented a Medicare payment system based on
      relative value units (RVUs). Today, RVUs are increasingly used to determine
      surgeon reimbursement from Medicare, Medicaid, and private third-party payers. We
      questioned whether current RVU assignments accurately reflect the quantity of
      time that surgeons spend operating. METHODS: Over a 12-month period, 59 common
      pediatric operations were identified and classified as general surgery (n = 34),
      urology (n = 13), or minimally invasive (n = 10). Only operations performed as an
      outpatient or requiring less than one inpatient day of direct surgeon involvement
      were included. By regression analysis, correlation coefficients were generated
      comparing average operating time per procedure to the corresponding RVU
      generated. RESULTS: Of 59 specific operations, a total of 744 general surgery
      cases, 1155 urological cases, and 370 minimally invasive cases were performed.
      RVU efficiency was greatest in general surgery (1 RVU = 5.18 operating minutes),
      followed by minimally invasive operations (1 RVU = 6.80 minutes) and urological
      operations (1 RVU = 8.59 minutes). Regression analysis proved minimally invasive
      operations to correlate best with RVUs with R2 = 0.8376, followed by urology at
      R2 = 0.6753, and then general surgery at R2 = 0.649. CONCLUSIONS: The RVU has
      emerged as the most dominant factor influencing reimbursement of practicing
      pediatric surgeons. Despite common surgeon bias, RVUs do correlate with current
      operating times. These data prove important as surgeons analyze cost, negotiate
      contracts, and strategically plan for fiscal success.

PMID- 16410142
TI  - Novel peptides secreted from human neuroblastoma: useful clinical tools?
AB  - BACKGROUND: Differentially expressed neuroblastoma (NB) proteins are vital for
      the development of new diagnostics and therapeutics. For example, secretory NB
      peptides (neuron-specific enolase and chromogranins) are clinically useful. We
      investigated polypeptide secretion by employing proteomic technologies to analyze
      proteins released from cultured NB cells. METHODS: Neuroblastoma cell lines (SK-N
      AS, SK-N-DZ, and SK-N-FI) were grown in serum-free media. Conditioned media from
      each cell line was analyzed for secreted proteins by 2-dimensional polyacrylamide
      gel electrophoresis. Selected polypeptides were identified by liquid
      chromatography-linked tandem mass spectrometry. RESULTS: We identified 5
      polypeptides that were secreted or shed by NB. Ubiquitin, beta2-microglobulin,
      insulin-like growth factor binding protein-2, superoxide dismutase (copper and
      zinc), and heat shock cognate 70-kd proteins were secreted from NB cells, as
      compared with control media. Elevated levels of these proteins have been
      described in serum/tissues under intracellular stress and malignancies, including
      NB. CONCLUSION: These novel secretory polypeptides may contribute to NB growth.
      The proteins may reveal additional tumor markers and permit putative use in the
      diagnosis and treatment of NB. Detection of these proteins in serum of children
      with NB vs controls (using 2-dimensional polyacrylamide gel electrophoresis and
      mass spectrometry techniques) is currently in progress.

PMID- 16410141
TI  - Total parenteral nutrition-associated hyperglycemia correlates with prolonged
      mechanical ventilation and hospital stay in septic infants.
AB  - PURPOSE: We studied the effects of total parenteral nutrition (TPN)-associated
      hyperglycemia on the clinical outcome in premature septic infants in the neonatal
      intensive care unit. METHODS: The charts of all premature infants weighing less
      than 1500 g upon admission to the neonatal intensive care unit between January 1,
      2002, and December 31, 2002, with sepsis, ventilator dependence, and feeding
      intolerance were studied. Maximum serum glucose concentrations were compared with
      duration of TPN, mechanical ventilation, hospital length of stay, and survival
      using Pearson regression analysis and Student's t test. RESULTS: Thirty-seven
      patients met the search criteria. The average caloric intake for all infants at
      the time of blood culture-proven sepsis was 83 +/- 19 kcal/kg per day. The
      maximum serum glucose concentration (milligrams per deciliter) after having
      positive blood cultures (sepsis) was positively correlated with the duration of
      TPN (r = 0.45, P = .005), length of dependence on mechanical ventilation (r =
      0.45, P = .006), and hospital length of stay (r = 0.36, P = .03). The average
      maximum serum glucose level was significantly higher in the nonsurviving infants
      (241 +/- 46 vs 141 +/- 48, P < .0001). CONCLUSION: Hyperglycemia correlated with
      prolonged ventilator dependency and increased hospital length of stay in
      premature septic infants. Avoidance of excessive nutrient delivery and tight
      glycemic control during periods of acute metabolic stress may improve outcome in
      this patient population.

PMID- 16410143
TI  - Differential sensitivity of chemoresistant neuroblastoma subtypes to MAPK
      targeted treatment correlates with ERK, p53 expression, and signaling response to
      U0126.
AB  - PURPOSE: Neuroblastoma tumors are comprised of neuroblastic (N), substrate
      adherent (S), and intermediate (I) cells. Because cell growth and differentiation
      often involve p44/p42 mitogen-activated protein kinase (MAPK) pathway signaling,
      we explored MAPK signaling and growth response in three NB cell types after MAPK
      kinase (MEK) inhibition to evaluate the feasibility of MAPK-targeted treatment
      strategies. METHODS: Three human NB cell cultures, SH-SY5Y (N-type), BE(2)-C (I
      type), and SK-N-AS (S-type), were treated in monolayer cultures with increasing
      concentrations of the MEK inhibitor U0126. MAPK pathway intermediates MEK and
      ERK, their activated (phosphorylated) forms p-MEK and p-ERK, and p53 expression
      were assessed by Western blot at 1 and 24 hours. At 72 hours, cell counts
      determined growth inhibition and DNA fragmentation ELISA assessed apoptosis.
      RESULTS: Among all three lines, total ERK and MEK expression were unaffected by
      U0126. However, constitutive total ERK and p53 expression were significantly
      greater in BE(2)-C (I-type) cells than in SH-SY5Y (N-type) and SK-N-AS (S-type).
      Active ERK (p-ERK) levels decreased in dose response to U0126 at 1 and 24 hours
      in all lines. Conversely, p-MEK levels increased with increasing U0126
      concentrations at 1 hour in SH-SY5Y (N-type) and at 24 hours in all lines. BE(2)
      C (I-type) cell counts decreased in concentration-dependent fashion with U0126,
      whereas SH-SY5Y (N-type) and SK-N-AS (S-type) showed a biphasic response with
      increased cell counts at 1 micromol/L U0126 and slightly decreased cell counts at
      10 mumol/L U0126. CONCLUSION: This study demonstrates that BE(2)-C (I-type) cells
      exhibit greater constitutive total ERK and p53 expression than SH-SY5Y (N-type)
      and SK-N-AS (S-type). Although all three lines exhibit p-ERK decreases with MEK
      inhibition, only BE(2)-C (I-type) cells significantly decrease their
      proliferation with U0126 treatment. Although MEK inhibition holds promise in
      targeting I-type NB cells, successfully treating this heterogeneous tumor may
      require combining agents against N- and S-type cells.

PMID- 16410144
TI  - Neuroblastoma impairs chemokine-mediated dendritic cell migration in vitro.
AB  - BACKGROUND/PURPOSE: Chemokine receptor (CCR7 [cysteine chemokine receptor 7]) and
      ligand (CCL19) interactions trigger dendritic cell (DC) recruitment from sites of
      antigen uptake to secondary lymphoid organs for T-cell priming and tumor lysis.
      Inhibition of this interaction may allow some aggressive tumors to evade immune
      detection. Although we have shown dysfunctional DC migration in murine
      neuroblastoma (NB) in vivo, the molecular mechanisms of impairment are unknown.
      We hypothesize that NB-induced aberrant CCR7-CCL19 signaling impairs DC
      migration. METHODS: Bone marrow-derived DCs were isolated from A/J mice (n = 24),
      matured, and cocultured with murine NB (TBJ) or media (control) for 7 days. CCR7
      and CCL19 protein and RNA expressions by control and NB-exposed DC were measured
      by flow cytometry, Western blot analysis, and polymerase chain reaction.
      Migration assays using Transwell plates (Corning Incorporated, Corning, NY, via
      Fisher Scientific, Pittsburgh, Pa) were performed with matured DC and CCL19.
      Furthermore, to determine if these changes in DC migration could be overcome,
      superphysiological concentrations of CCL19 (100 ng/mL) were used. Results are
      reported as the average percentage +/- SD. RESULTS: No significant differences in
      CCR7 or CCL19 protein expression between tumor and control were seen at 7 days.
      However, NB significantly decreased CCL19-induced migration by more than 50%:
      control (26.48% +/- 1.52%) vs DC cocultured with TBJ (12.7% +/- 0.3%) (P < .05).
      Superphysiological doses up to 100 ng/mL CCL19 showed no significant upregulation
      in migration in DC cocultured with tumor cells. CONCLUSIONS: Although in vitro
      coculture with NB does not induce significant changes in either CCR7 or CCL19
      expression, profound functional impairments in CCR7/CCL19-mediated migration
      occurs. These findings suggest that intracellular signal transduction pathways
      for these chemokines may be impaired by tumor. Targeting this chemokine-receptor
      pathway may provide a novel therapeutic strategy.

PMID- 16410145
TI  - Structural analysis of the human neuroblastoma DNA replication complex: insights
      into faulty proliferation.
AB  - BACKGROUND: Whether faulty DNA synthesis contributes to neuroblastoma (NB)
      pathogenesis has received little attention. We have shown that NB DNA replication
      is orchestrated by a multiprotein DNA replication complex (DNA synthesome) which
      mediates error-prone DNA synthesis. We sought to define proteomic alterations of
      the NB DNA synthesome, which lead to lowered replication fidelity. METHODS: DNA
      synthesomes from NB and neural stem (NS) cell culture were purified. Proteomic
      differences of the DNA synthesome between NB and NS cells were determined using 2
      dimensional polyacrylamide gel electrophoresis and immunodetection. RESULTS: DNA
      synthesome proteins from NB and NS cells were compared. Only replication protein
      A (RPA) showed distinct changes. RPA from NS cells resolved as a single spot
      (isoelectric point [pI] 5.75), whereas RPA in NB showed a main spot (pI 5.75)
      along with 3 additional isoforms. RPA binds to single-stranded DNA and
      participates in protein-protein interactions. CONCLUSIONS: NB DNA synthesome
      showed 3 distinct isoforms of RPA when compared with NS cells. These findings are
      significant in that it is possible to link changes in the fidelity of DNA
      replication with a specific protein alteration of the NB DNA synthetic apparatus.
      The novel RPA forms may be a new signature of NB malignancy.

PMID- 16410146
TI  - Excellent local tumor control regardless of extent of surgical resection after
      treatment on the Chicago Pilot II protocol for neuroblastoma.
AB  - BACKGROUND: Our aim was to investigate the impact of the extent of surgical
      resection on local recurrence and survival in high-risk patients treated with the
      Chicago Pilot II protocol. METHODS: Retrospective chart review was performed on
      30 patients enrolled in the Chicago Pilot II protocol between 1995 and 2003.
      Variables studied were location of tumor, extent of resection, timing and
      location of recurrence, MYCN amplification, surgical complications, event-free
      survival, and overall survival (OS). Operative reports and postoperative meta
      iodobenzylguanidine scans were used to assess extent of resection. Complete
      resection (CR) was defined as no gross residual tumor including primary and nodal
      disease. RESULTS: Three-year event-free survival and OS of this cohort of 30
      patients was 58% and 82%, respectively. Only 1 patient developed a local
      recurrence, whereas metastatic recurrent disease was observed in 13 (43%) of the
      30; and this subset had a significantly worse OS (23% vs 94%, P = .001). The most
      common relapse location was in bone. Patients with incomplete resection (IR)
      (11/30) and CR (19/30) had recurrence rates of 64% (7/11) and 32% (6/19, P =
      .12), respectively. Event-free survival was significantly better for patients
      with CR (68%) vs IR (27%; P = .05; odds ratio, 2.9). Overall survival rates for
      patients with CR vs IR were 68% vs 55%, respectively (P = .25). CONCLUSIONS:
      Recurrence rate was the significant determinant of survival. Patients with CR had
      lower recurrence rates; however, they did not have improved local control. Final
      outcome of patients with unfavorable neuroblastoma will be determined by
      metastatic recurrence, not by extent of resection.

PMID- 16410147
TI  - Pediatric trauma nurse practitioners provide excellent care with superior patient
      satisfaction for injured children.
AB  - PURPOSE: Work hour restrictions for house staff have forced a reevaluation of the
      traditional roles of all health care providers. In 2001, our level I pediatric
      trauma center augmented the role of our trauma pediatric nurse practitioners
      (PNPs) to include in-patient management. We hypothesized that a PNP can provide
      injured children a level of care commensurate with a resident (RES). METHODS: All
      children between 2 months and 17 years old admitted to the Trauma Service were
      considered for the study. Patients were randomized to PNP or RES care groups.
      Types of injuries, injury severity score, missed injuries, readmissions, hospital
      length of stay (LOS), and cost were recorded. Satisfaction surveys were
      administered to all families. RESULTS: A total of 76 children were enrolled.
      During the study period, there were no missed injuries or readmissions. The PNP
      group had a significantly shorter LOS and received significantly higher
      satisfaction survey scores with regard to information on injuries, tests and
      treatment, and frequency of visits provided to the patient/family. CONCLUSIONS:
      PNPs provide equivalent care for injured children with significantly shorter LOS
      and higher patient satisfaction than RESs. In-patient trauma nurse practitioners
      provide added value to the care of the injured child in the era of reduced RES
      work hours.

PMID- 16410149
TI  - RE: "Thoracoscopic repair of H-type tracheoesophageal fistula in the newborn: a
      technical case report" in the Journal of Pediatric Surgery [October
      2004;39(10):1568-70].

PMID- 16410150
TI  - Instability of calcium channel antagonists during sample preparation for LC-MS-MS
      analysis of serum samples.
AB  - 1,4-Dihydropyridines calcium channel antagonists (1,4-DHP CCAs) are photolabile
      and the products of their photodecomposition have no pharmaceutical activity. In
      our previous work we have presented a screening procedure for eleven 1,4-DHPs in
      plasma by LC-MS-MS using multiple reaction motoring. The laboratory process
      includes preparation and storage of stock solutions, plasma storage, solid-phase
      extraction, reconstitution of extracts and storage time in an autosampler for LC
      MS-MS analysis. Prior to validation of the analytical procedure, we have tested
      the stability of these compounds by exposure to light. Methanolic solutions have
      been exposed to laboratory and UV light and the stability of the compounds in
      plasma was tested by exposure of spiked plasma samples to laboratory light at
      room temperature. Stability during freeze-thaw cycles and stability during 2
      month storage at -20 degrees C have been tested as well. Products of
      photodecomposition have been identified after forced degradation and the degree
      of degradation has been quantified using LC-UV-DAD and LC-MS-MS, respectively. A
      96% degradation after only 2h has been observed when solutions of nifedipine or
      nisoldipine were exposed to laboratory light in clear glass vials. In plasma
      samples degradation was 25% in only 2h for both compounds. The main degradation
      product was produced by oxidation of the dihydropyridinic ring resulting in the
      pyridine analogue that has been described as the first metabolite in the
      metabolic pathway. Only minor degradation was found for the other tested
      compounds after 2h light exposure in methanolic solutions. Furthermore,
      lercanidipine and nicardipine were also degradated by esterhydrolysis. Several
      additional minor degradation products were found for the other tested 1,4-DHPs,
      however, some of them could not be identified. Preconditions for storage and
      handling of plasma samples prior to and during analysis for 1,4-DHP CCAs are
      suggested in order to avoid photodecomposition of the analytes.

PMID- 16410151
TI  - Comparison of ethanol concentrations in right cardiac blood, left cardiac blood
      and peripheral blood in a series of 30 cases.
AB  - The aim of this study was to compare ethanol concentrations in right cardiac
      blood, left cardiac blood and peripheral blood. Samples were taken from a series
      of 30 medicolegal autopsies. Ethanol was measured by headspace GC-FID. In each
      case, the degree of putrefaction, chest or abdominal injury, and/or regurgitation
      of gastric contents into the airways were noted. Our results show that there
      exists in certain cases a marked increase in ethanol concentration in left
      cardiac blood compared with right cardiac blood and peripheral blood. In these
      cases, we observed (i) a high concentration of ethanol in the gastric contents
      and (ii) regurgitation of gastric contents into the airways. The authors discuss
      the post-mortem redistribution mechanisms which could explain these results and
      stress the value of sampling right cardiac blood at autopsy.

PMID- 16410152
TI  - Automated comparison of firearm bullets.
AB  - Fired bullets bear striation marks that can be thought of as a "fingerprint" left
      by the firearm. This new comparison approach is based on an automated extraction
      of a "signature" encompassing the relevant marks from an image. To this end,
      multiple pictures of the bullet are recorded first by using different
      illumination patterns, and a high quality image is generated by means of fusion
      techniques. After a preprocessing, the image intensities are filtered along the
      striations direction, yielding a compact representation of the marks. A non
      linear filter selects the striae of interest. The actual comparison takes place
      by cross-correlating the signatures obtained this way. Finally, an assessment
      strategy is proposed to objectively evaluate the performance of the system. As
      demonstrated with an image database of real bullets, the proposed approach
      outperforms a state-of-the-art commercial system.

PMID- 16410154
TI  - Nuclear forensic investigations: two case studies.
AB  - This paper describes the methodology and analytical methods used in nuclear
      forensic investigations. Two case studies are taken as examples to illustrate
      this. These examples represent typical cases that have been analysed at the
      Institute for Transuranium Elements (ITU) since last 10 years, i.e. the beginning
      of the illicit trafficking of nuclear materials. Results of the various
      analytical techniques are shown, which, together with other type of information,
      reveal the origin of the material.

PMID- 16410153
TI  - Lethal enterovirus-induced myocarditis and pancreatitis in a 4-month-old boy.
AB  - After inconspicuous pregnancy and birth, a 16-year-old mother presented her male
      baby 5 days later with severe diarrhoea and vomiting. During the following weeks,
      the child temporarily showed hypotension, hypothermia and increased body
      temperature, bradyarrythmia with apnoea, continuing diarrhoea, sometimes vomiting
      and developed signs of pancreatic insufficiency. Due to increasing loss of weight
      and obviously severe dystrophia, parenteral nutrition had to be initiated. All
      clinical investigations revealed no underlying disease. Numerous biopsies, mainly
      from the gastrointestinal tract were taken, but no relevant pathological findings
      were disclosed. The baby was found lifeless by his mother, 4 months after birth.
      According to the death certificate, the physicians regarded the lethal outcome as
      a case of sudden infant death syndrome (SIDS). Histological and
      immunohistochemical investigations of organ samples revealed signs of
      myocarditis, pancreatitis and focal pneumonia. Molecularpathological techniques
      were used to detect enterovirus RNA from tissue samples from the myocardium,
      liver and pancreas. Enteroviral myocarditis with concomitant pancreatitis was
      determined as cause of death.

PMID- 16410155
TI  - Allele frequencies for 15 short tandem repeat loci in a representative sample of
      Bosnians and Herzegovinians.
AB  - Allele frequencies for the 15 STR loci (D3S1358, TH01, D21S11, D18S51, Penta E,
      D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX, FGA)
      included in the PowerPlex 16 kit were obtained from a multiethnic sample of 100
      unrelated individuals born in Bosnia and Herzegovina.

PMID- 16410156
TI  - Y chromosomal STR haplotypes in the northeastern China Han population.
AB  - Haplotype frequencies of 20 Y chromosome STR loci, DYS19, DYS385 (a/b), DYS389
      (I, II), DYS390, DYS391, DYS393, DYS434, DYS435, DYS437, DYS438, DYS439, DYS441,
      DYS442, DYS444, DYS445, DYS446, DYS452 and DYS456 were determined from a sample
      of 122 unrelated males in the northeastern China Han populations.

PMID- 16410158
TI  - Alcohol metabolism of local Chinese in Hong Kong: a statistical determination on
      the effects of various physiological factors.
AB  - A study was designed to examine the elimination rate of alcohol from the body of
      the local Chinese after consumption of different types of alcoholic drinks. The
      breath alcohol of 184 healthy volunteers was determined and converted into blood
      alcohol levels after they finished drinking. Information on the type and volume
      of alcoholic drinks consumed, age group, sex, drinking habit, and drinking on
      empty stomach or with/after meal was recorded for each participant. The results
      show that the elimination rate of an individual can be explained in terms of
      physiological variables including sex and drinking habit. The determined
      elimination rates allow forensic toxicologists to back calculate the blood
      alcohol concentration (BAC) of the drivers at the time of accident in drunk
      driving cases. The elimination rates of blood alcohol at 95% prediction intervals
      for male and female are in the range of 9.5-23.8 mg/100 ml/h and 11.1-37.1 mg/100
      ml/h, respectively.

PMID- 16410157
TI  - Determination of morphine in postmortem rabbit bone marrow and comparison with
      blood morphine concentrations.
AB  - The aim of this study is to predict how long after time of death a buried body
      could be analyzed for opiates in soft tissues and to show the accessibility and
      suitability of bone marrow as a useful toxicological specimen from buried bodies.
      Morphine solutions were injected in nine albino rabbits. Doses ranged from 0.3 to
      1.1 mg/kg with 0.1 mg/kg increments. One hour after the injections, the rabbits
      were sacrificed. Blood, urine and bone marrow samples were collected for
      analysis. After the whole bodies were buried, femur bone marrow specimens were
      collected on the seventh and fourteenth days. CEDIA was used to monitor morphine
      contents of the collected samples. All experimental cases showed that the
      increase in the given morphine doses correlated with the increase in blood and
      bone marrow morphine concentrations. High morphine concentrations were detected
      in urine samples, but there was no correlation between the urine and blood or
      urine and bone marrow morphine concentrations. Statistically meaningful increases
      in bone marrow morphine concentrations were found parallel to increase of blood
      morphine concentrations. Seventh and fourteenth day postmortem morphine
      concentrations also followed this correlation. Morphine concentrations in bone
      marrow at 7 and 14 day postmortem decreased consistently when compared with bone
      marrow morphine concentrations collected immediately after death. We conclude
      that in sudden death when other specimens are unavailable due to degradation,
      bone marrow can be a most useful specimen. Further experimental research in this
      area is required to validate bone marrow as an alternative tissue.

PMID- 16410159
TI  - An evaluation of the Cozart RapiScan system as an on-site screening tool for
      drugs of abuse in a non-conventional biological matrix: vitreous humor.
AB  - The aim of this project was to evaluate the Cozart RapiScan Oral fluid Drug
      Testing System as an on-site screening tool for vitreous humor samples collected
      during post-mortem examinations. Vitreous humor is easy to collect and as it is
      contained within the eye it is almost completely unaffected by post-mortem
      redistribution. The ability to carry out an initial drug screen on vitreous humor
      at the earliest stage of the death investigation process could contribute
      significantly to the assessment of the role drugs may have played prior to
      confirmation with toxicological analyses at the laboratory. Vitreous humor (n =
      146) was collected from autopsy examinations (111 males and 35 females) with a
      specific focus on cases where death occurred following a road traffic accident or
      where an overdose was suspected. All samples were screened using the five-panel
      methadone Cozart RapiScan Cartridge with an overall positive rate of 29%. Of the
      positive results, 43% screened positive for benzodiazepines, 17% for cocaine, 7%
      for methadone and 33% for opiates. Positive samples, with the exception of
      benzodiazepines, and 20% of negative samples were analysed by GC/MS. This is the
      first reported use of this system as an on-site forensic tool in death
      investigation and for screening for drugs of abuse in vitreous humor. The
      conclusions from this study show that the Cozart RapiScan System could play an
      important role in obtaining information on the toxicological state of the person
      at the time of death.

PMID- 16410160
TI  - Quantitation of atenolol, metoprolol, and propranolol in postmortem human fluid
      and tissue specimens via LC/APCI-MS.
AB  - Hypertension is a growing medical concern in the United States. With the number
      of Americans suffering from hypertension increasing, the use of antihypertensives
      such as beta-blockers is increasing as well. In fact, three beta-blockers -
      atenolol, metoprolol and propranolol - were among the 200 most prescribed
      medications in the United States in 2003. Pilots that successfully manage their
      hypertension can remain certified to fly. The Federal Aviation Administration
      currently designates approximately 8% of active pilots as "hypertensive with
      medication". The Civil Aerospace Medical Institute (CAMI) performs toxicological
      evaluation on victims of fatal aviation accidents. At CAMI beta-blockers are
      analyzed using gas chromatography with mass spectrometric detection. We have,
      however, recently developed a liquid chromatography with mass spectrometric
      detection (LC/MS) method for the simultaneous quantitation of three commonly
      prescribed beta-blockers, atenolol, metoprolol and propranolol. One advantage of
      our LC/MS method is the specificity provided by an ion trap MS. Utilizing an ion
      trap MS, we were able to conduct MS/MS and MS/MS/MS on each analyte. This method
      also eliminates the time-consuming and costly derivitization step necessary
      during GC/MS analysis. Additionally, by utilizing this novel method, any concerns
      about beta-blocker metabolite and/or sample matrix interference are eliminated.
      The limits of detection for this method ranged from 0.39 to 0.78 ng/mL and the
      linear dynamic range was generally 1.6-3200 ng/mL. The extraction efficiencies
      for each analyte ranged from 58% to 82%. This method was successfully applied to
      postmortem fluid and tissue specimens obtained from victims of three separate
      aviation accidents.

PMID- 16410161
TI  - Results of hair analyses for drugs of abuse and comparison with self-reports and
      urine tests.
AB  - Urine as well as head and pubic hair samples from drug abusers were analysed for
      opiates, cocaine and its metabolites, amphetamines, methadone and cannabinoids.
      Urine immunoassay results and the results of hair tests by means of gas
      chromatography-mass spectrometry were compared to the self-reported data of the
      patients in an interview protocol. With regard to the study group, opiate abuse
      was claimed from the majority in self-reports (89%), followed by cannabinoids
      (55%), cocaine (38%), and methadone (32%). Except for opiates the comparison
      between self-reported drug use and urinalysis at admission showed a low
      correlation. In contrast to urinalysis, hair tests revealed consumption in more
      cases. There was also a good agreement between self-reports of patients taking
      part in an official methadone maintenance program and urine test results
      concerning methadone. However, hair test results demonstrated that methadone
      abuse in general was under-reported by people who did not participate in a
      substitution program. Comparing self-reports and the results of hair analyses
      drug use was dramatically under-reported, especially cocaine. Cocaine hair tests
      appeared to be highly sensitive and specific in identifying past cocaine use even
      in settings of negative urine tests. In contrast to cocaine, hair lacks
      sensitivity as a detection agent for cannabinoids and a proof of cannabis use by
      means of hair analysis should include the sensitive detection of the metabolite
      THC carboxylic acid in the lower picogram range.

PMID- 16410162
TI  - Mitochondrial DNA sequence alterations observed between blood and buccal cells
      within the same individuals having betel quid (BQ)-chewing habit.
AB  - There are hundreds of millions of betel quid (BQ) lovers widely spreading around
      the world. Compositions in BQ may generate reactive oxygen species, which would
      induce DNA damage. However, oral epithelial cells as well as blood have often
      been used as reference samples in comparison with the mitochondrial DNA (mtDNA)
      sequence of hairs. The main purpose of this study was to investigate the extent
      of mtDNA sequence variation in regular BQ-chewers' oral epithelial cells, and
      thus to evaluate the forensic availability of the buccal cells from BQ-chewers
      using the mtDNA markers. The hypervariable segments I and II in the D-loop
      control region of mtDNA between paired samples of blood and buccal scrape cells
      from 75 non-BQ-chewers (to be a control group), 60 BQ-chewers, and 67 oral
      cancerous patients were DNA sequenced and compared. Among the three groups, the
      alteration rates of 1.3% (1 out of 75), 10% (6 out of 60), and 61% (41 out of 67)
      were identified from the control, BQ-chewers, and the cancerous group,
      respectively. In the cancerous group, as expected, high rate of DNA alteration
      between blood and buccal samples was found. In the BQ-chewers, one and five
      individuals had the length and point alterations, respectively. Interestingly,
      most of point alteration sites, e.g., mtDNA positions 153, 16189, 16093
      identified from BQ-chewers, were also observed in previous literatures. As for
      the control subjects, one case with point alteration, and none with length
      alteration, was identified. For all the three groups, not only the oral cells but
      also the normal blood samples exhibited high frequency (>55%) of length
      heteroplasmy at poly-(C)n track. Statistical analyses revealed that significance
      was observed between the severity of mtDNA alteration in BQ-chewers' oral
      epithelial cells and the history of BQ-chewing (p = 0.02), with a tendency of
      positive association. Based on the guidelines by Carracedo et al., we suggest
      that the interpretation of mtDNA variations between criminal evidences and the
      oral epithelial cells (as a reference or known sample) from BQ-chewers should be
      performed with particular caution using the PCR-based mtDNA sequencing. Our
      findings would be valuable in mtDNA analysis of hair evidence, especially for
      those countries where the habit of BQ-chewing is popular.

PMID- 16410163
TI  - Spectrophotometric and tristimulus analysis of the colors of subcutaneous
      bleeding in living persons.
AB  - The colorimetric patterns of color changes of skin bruises were examined in adult
      male Japanese volunteers wounded by a sharp pinch on the inside of the upper arm
      and forearm. In most cases the non-traumatic area near the bruise could be used
      for the control skin. By using a colorimeter, tristimulus and spectrophotometric
      methods were available to objectively analyze the skin discoloration. On the
      L*a*b* color space analysis, Deltab*, the difference between the lesion and
      control area, was useful to judge whether a bruise was recent or older. When it
      showed a minus value, the bruise was diagnosed as recent within 2 days. The
      temporal course of Deltab* changes may be a good indication of the time of
      bruising as measured in days, however, in actual forensic analysis situations, it
      is difficult to measure changes in the skin area on a living person over several
      days. It was hard to perform further age analyses on older bruises especially
      where only one or two measurements had been taken. On spectrophotometric
      analysis, clear differences of spectral reflectance curves in some wavelength
      regions were observed in recent, older and nearly healed lesions as compared with
      controls. The characteristics of new bruises had a peak point around 500-520 nm
      of the green area and absorbed light remarkably in the green, yellow and orange
      wavelength regions (approximately 520-640 nm). On older lesions, reflectance in
      the blue and one portion of the green wavelength region (440-520 nm) remained
      unchanged or further reduced before approximately ending similarly to the control
      curve. Nearly healed injuries showed slight reductions of reflectance over wide
      wavelength regions, but the curves were close to that of control skin. These
      reflectance graph patterns could cope with the temporal sequence of color changes
      of a bruise. As individual reflectance graph patterns depended on particular
      factors, such as the degree of bruising, it was difficult to correspond the
      patterns of all bruises to the date of bruising. However, if two measurements
      were taken at 1 or 2 days, their validity for classifying into recent, older and
      nearly healed bruises, might be shown by comparing patterns of both curves
      patterns including the control area. Some indices using reflectance values on
      certain wavelengths were not very useful to pinpoint the time of bruising. On
      spectrophotometric analysis, the evaluation of the age of a bruise needs to be
      done by a comparison of reflectance graph patterns in wide wavelengths in visible
      light regions.

PMID- 16410164
TI  - Is there progress in the autopsy diagnosis of sudden unexpected death in adults?
AB  - Sudden death is now currently described as natural unexpected death occurring
      within 1h of new symptoms. Most studies on the subject focused on cardiac causes
      of death because most of the cases are related to cardiovascular disease,
      especially coronary artery disease. The incidence of sudden death varies largely
      as a function of coronary heart disease prevalence and is underestimated.
      Although cardiac causes are the leading cause of sudden death, the exact
      incidence of the other causes is not well established because in some countries,
      many sudden deaths are not autopsied. Many risk factors of sudden cardiac death
      are identified: age, gender, heredity factors such as malignant mutations, left
      ventricular hypertrophy and left ventricle function impairment. The role of the
      police surgeon in the investigation of sudden death is very important. This
      investigation requires the interrogation of witnesses and of the family members
      of the deceased. The interrogation of physicians of the rescue team who attempted
      resuscitation is also useful. Recent symptoms before death and past medical
      history must be searched. Other sudden deaths in the family must be noted. The
      distinction between sudden death at rest and during effort is very important
      because some lethal arrhythmia are triggered by catecholamines during stressful
      activity. The type of drugs taken by the deceased may indicate a particular
      disease linked with sudden death. Sudden death in the young always requires
      systematic forensic autopsy performed by at least one forensic pathologist.
      According to recent autopsy studies, coronary artery disease is still the major
      cause of death in people aged more than 35 years. Cardiomyopathies are more
      frequently encountered in people aged less than 35 years. The most frequent
      cardiomyopathy revealed by sudden death is now arrhythmogenic right ventricular
      cardiomyopathy also known simply as right ventricular cardiomyopathy (RVC). The
      postmortem diagnosis of cardiomyopathies is very important because the family of
      the deceased will need counseling and the first-degree relatives may undergo a
      possible screening to prevent other sudden deaths. In each case of sudden death,
      one important duty of the forensic pathologist is to inform the family of all
      autopsy results within 1 month after the autopsy. Most of the recent progress in
      autopsy diagnosis of sudden unexpected death in the adults comes from molecular
      biology, especially in case of sudden death without significant morphological
      anomalies. Searching mutations linked with functional cardiac pathology such as
      long-QT syndrome, Brugada syndrome or idiopathic ventricular fibrillation is now
      the best way in order to explain such sudden death. Moreover, new syndromes have
      been described by cardiologists, such as short-QT syndrome and revealed in some
      cases by a sudden death. Molecular biology is now needed when limits of
      morphological diagnosis have been reached.

PMID- 16410165
TI  - Growth rates of the blowfly, Lucilia sericata, on different body tissues.
AB  - Estimates of post-mortem interval based on forensic analysis of the age of
      blowfly larvae on a corpse, are generated from standardised larval development
      curves. These are derived from studies of the growth of larvae reared, usually,
      on liver and at a range of temperatures. However, it is possible that the species
      or organ on which the larvae feed, might significantly alter the rate of growth.
      The present study therefore compared the development of the blowfly Lucilia
      sericata (Meigen) (Diptera: Calliphoridae) fed on lung, liver and heart, from
      both cows and pigs. Half of the tissue samples used were liquidised while half
      were not, to assess whether structural differences in the food source were
      important. Larvae grew significantly faster and gave rise to larger adults when
      reared on pig compared to cow tissue and when reared on lung and heart compared
      to liver. Larvae completed feeding and wandered from the food source 31h earlier
      and grew 2mm longer when reared on lung compared to liver. Tissue structure had
      no or little effect on development. For the forensic entomologist, these results
      highlight the importance of recording the position of larvae removed from a body
      and the care that should be used when extrapolating development rates from
      standard curves based on larvae fed on only a single medium, particularly where
      that is liver.

PMID- 16410166
TI  - Analysis of jumping/falling distance from a height.
AB  - The kinematic motion analysis of 50 jumps from a height of 5m demonstrated
      distinguishable maxima of jumping distances between passive and active jumps (1.0
      3.4 and 3.7-7.1 m, respectively). The variation of several parameters concerning
      the 'take-off' mechanism showed less influence regarding the jumping distances.
      The congruence of the trajectory of the 'free-flight' domains of the jumps and
      the simple model for the parabola of an inclined throw has been proven. Thus, a
      prediction of the distance range for heights up to 20 m was extrapolated.

PMID- 16410167
TI  - Sudden infant death: lingual thyroglossal duct cyst versus environmental factors.
AB  - An 8-month-old female baby was found collapsed in the prone position 30 min after
      being positioned under soft-bedding. She was taken to the emergency room with
      cardiopulmonary arrest. Her heartbeat was recovered after resuscitation and
      continued for 20 h under artificial respiration, at which point the child died.
      At autopsy, the child showed no significant pathological abnormalities apart from
      a thyroglossal duct cyst of 2.0 cm diameter, therefore, it seemed that the cyst,
      which was close to the epiglottis, had caused asphyxia through airways occlusion.
      However, the child had shown no respiratory problems before death, and the risk
      of airway occlusion as a result of lingual cysts is more likely in a supine
      rather than a prone position. A small amount of evidence suggested that the child
      died as a result of suffocation from being covered by soft-bedding, which could
      have caused fatal asphyxia; it is also possible that a hypoxic state induced by
      airway obstruction might have been enhanced by being covered with bedding. It
      seemed reasonable to assume that death was caused by a combination of the lingual
      thyroglossal duct cysts and asphyxia caused by being covered in bedding, though
      the main factor appeared to be the large cyst.

PMID- 16410168
TI  - Computer simulation of the accident with nine victims.
AB  - In the paper we wish to emphasise the significance of vehicle driving dynamics
      analysis in the collision phase and occupant load analysis by means of using a
      software environment. Thereby we also wish to present the results of the
      simulation of the course of a traffic accident with nine victims that arose from
      a collision between an Audi A6 passenger car and the VW Caravelle van. In
      treating the traffic accident the forensic expert was faced with the questions
      about what caused the injuries to the front passenger in the Audi A6 passenger
      car, about the way the two vehicles had collided, about their collision
      velocities, about the way the two vehicles were handled and about the causes that
      originated the traffic accident. The critical situation on the road was a
      consequence of the tiredness of the van driver, the inadequate use of the passive
      safety systems and overloading the van.

PMID- 16410169
TI  - Allele frequencies for 27 Y-STR loci with U.S. Caucasian, African American, and
      Hispanic samples.
AB  - A total of 263 U.S. Caucasians, 260 African Americans and 140 U.S. Hispanics or a
      subset of 31 Caucasians, 32 African Americans, and 32 Hispanics were typed for 27
      Y-chromosome short tandem repeat (Y-STR) markers: DYS444, DYS446, DYS449, DYS463,
      DYS485, DYS490, DYS495, DYS504, DYS505, DYS508, DYS520, DYS522, DYS525, DYS532,
      DYS533, DYS534, DYS540, DYS556, DYS557, DYS570, DYS575, DYS576, DYS594, DYS632,
      DYS635, DYS641, and DYS643. Allele frequencies for each locus are reported along
      with nomenclature based on sequence analysis.

PMID- 16410170
TI  - Y-chromosome STR haplotypes in East Timor: forensic evaluation and population
      data.

PMID- 16410171
TI  - Validation of a large Italian Database of 15 STR loci.
AB  - Results from a collaborative exercise with proficiency testing conducted by 20
      Italian laboratories on the 15 loci included in the Identifiler kit were analyzed
      by allele sharing methods and by standard population genetics tests. The
      validated database, including about 1500 subjects, was merged with that of a
      previous exercise conducted on nine loci, and the resulting allele frequencies,
      subdivided by Italian region, were published on-line.

PMID- 16410173
TI  - Multiple echo diffusion tensor acquisition technique.
AB  - The standard method of diffusion tensor imaging (DTI) involves one diffusion
      sensitizing gradient direction per acquired signal. This paper describes an
      alternative method in which the entire direction set required for calculating the
      diffusion tensor is captured in a few scans. In this method, a series of
      radiofrequency (RF) pulses are applied, resulting in a train of spin echoes. A
      pattern of applied magnetic field gradients between the RF pulses generates a
      different diffusion weighting in both magnitude and direction for each echo,
      resulting in a dataset sufficient to determine the tensor. This significantly
      reduces the time required for a full DTI scan and potentially allows a tradeoff
      of this time for image quality. In the present work, this method is demonstrated
      in an anisotropic diffusion phantom (asparagus).

PMID- 16410172
TI  - The cost of parallel imaging in functional MRI of the human brain.
AB  - While the advantages of parallel acquisition techniques for echo-planar imaging
      (EPI) are well documented for studies affected by magnetic field inhomogeneities,
      this work focuses on the costs in functional MRI of brain regions without
      artifacts due to susceptibility effects. For a visual stimulation paradigm and
      relative to conventional EPI (2.9 T; TR/TE=2000/36 ms), the use of parallel
      acquisition at a reduction factor of 2 decreased the mean number of activated
      voxels by 21% at 2 x 2 x 2-mm(3) resolution (n=6) and by 15% at 3 x 3 x 3-mm(3)
      resolution (n=6). The loss of sensitivity reflects both a decreased signal-to
      noise ratio of the native images due to a lower number of contributing gradient
      echoes and a decreased BOLD MRI sensitivity due to the coverage of a smaller
      range of TEs.

PMID- 16410174
TI  - Evaluation of diffusional anisotropy and microscopic structure in skeletal
      muscles using magnetic resonance.
AB  - The pulsed-gradient spin-echo (PGSE) nuclear magnetic resonance (NMR) method is
      used for detecting the diffusion of water molecules in biological tissues.
      Because tissues generally have diffusional anisotropy, their diffusion properties
      are denoted by a tensor. In this study, we evaluated the diffusional anisotropy
      and microscopic structure in atrophied skeletal muscles using the PGSE NMR
      method. The left sciatic nerve was severed in twelve 9-week-old rats. Neurotomy
      caused neurogenic muscular atrophy at the left gastrocnemius. At 2, 4 and 8 weeks
      after neurotomy, magnetic resonance signals were selectively acquired from a 2 x
      2 x 2 mm(3) voxel, which was located on the left gastrocnemius. The diffusion
      tensor, the mean diffusivity (MD) and the fractional anisotropy (FA) were
      calculated from the signals. A theoretical model of the diffusion in muscles was
      derived from Tanner's equation. The muscle fiber diameter was estimated by
      fitting the model to the measured signals. The measurements were also performed
      for normal rats as controls. No significant difference was found in the MD and
      the estimated intracellular diffusion coefficient between the control group and
      the denervated group. The denervated group had significantly higher FA compared
      with the control group (P<.05). The estimated muscle fiber diameter of the
      denervated group was significantly smaller than the estimated value of the
      control group (P<.05). These differences were found at 8 weeks after neurotomy.
      The proposed method is effective for evaluating changes in the microscopic
      structure of skeletal muscles.

PMID- 16410175
TI  - Compatibility of Gd-DTPA perfusion and histologic studies of the brain.
AB  - Histology, including immunohistochemistry, and magnetic resonance imaging
      microscopy (microMRI) are complementary techniques for the analysis of brain
      structure. Therefore, microMRI analysis, often of formalin-fixed tissue, precedes
      histologic evaluation of the same experimental animal in many studies. However,
      the application of gadopentetate dimeglumine (Gd-DTPA), while of value for MRI
      studies, has an unknown effect on subsequent histology. We demonstrate here that
      for the mouse brain, histology with Nissl staining and immunostaining for
      microtubule-associated protein 2, using standard techniques for tissue
      preparation, are unaffected by prior perfusion of the tissue with Gd-DTPA. This
      conclusion was based on qualitative morphologic comparisons of stained sections,
      as well as quantification of mean immunofluorescence pixel intensities from Gd
      treated (mean+/-S.D.=131.2+/-28.4; n=3) as compared to nontreated specimens
      (116.2+/-34.7; n=3, P=.7). Therefore, Gd-DTPA may be applied as a microMRI
      contrast agent in formalin-fixed brain tissue prior to histologic studies.

PMID- 16410176
TI  - Measurement of in vivo multi-component T2 relaxation times for brain tissue using
      multi-slice T2 prep at 1.5 and 3 T.
AB  - The objective of this study was to implement a clinically relevant multi-slice
      multi-echo imaging sequence in order to quantify multi-component T2 relaxation
      times for normal volunteers at both 1.5 and 3 T. Multi-echo data were fitted
      using a nonnegative least square algorithm. Twelve echo data with nonlinear echo
      sampling were acquired using a receive-only eight-channel phased array coil and
      volume head coil for phantoms and normal volunteers, and compared to 32-echo data
      with linear echo sampling. It was observed that the performance of the 180
      degrees refocusing trains was more spatially uniform for the receive-only eight
      channel phased array coil than for the head coil, particularly at 3 T. The
      phantom study showed that the estimated T2 relaxation times were accurate and
      reproducible for both single- and multi-slice acquisition from a commercial
      phantom with known T2 relaxation times. Short T2 components (T2 <50 ms) were
      mainly observed within the white matter for normal volunteers, and the fraction
      of short T2 water components (i.e., myelin water) was 7-12% of total water. It
      was observed that the calculated myelin water fraction map from the nonlinearly
      sampled 12-echo data was comparable with that from the linearly sampled 32-echo
      data. Quantification of T2 relaxation times from multi-slice images was
      accomplished with a clinically acceptable scan times (16 min) for normal
      volunteers by using a nonselective T2 prep imaging sequence. The use of the eight
      channel head coil involved more accurate quantification of T2 relaxation times
      particularly when the number of echoes was limited.

PMID- 16410177
TI  - The activation of the cortical hand area by toe tapping in two bilateral upper
      extremities amputees with extraordinary foot movement skill.
AB  - Functional reorganization of the human brain after an arm amputation has been
      documented in several investigations, but as far as we know, there has been no
      report on amputees with skilled foot movement ability. To further assess the
      power of functional reorganization of the brain after an amputation, we
      investigated two bilateral upper-extremities amputees who were professional
      sculptors and painters with their feet. Performance tests showed that they
      possessed high foot movement ability. Functional MRI data indicated that toe
      tapping of the amputees not only activated the classical foot primary motor
      cortex, but also activated the hand area. In the T1-weighted MRI, the central
      sulci of both amputees kept their characteristic shape. Our study suggests that
      there is a remarkable power of neural plasticity in the motor cortex, and the
      maturation of the cortex develops in response to daily practice. The possible
      mechanisms of the reorganization are tentatively discussed.

PMID- 16410178
TI  - Spin-lock MRI with amplitude- and phase-modulated adiabatic waveforms: an MR
      simulation study.
AB  - INTRODUCTION: Image contrast between tissue types can be generated based on their
      T1/T2 ratio using spin-lock MRI techniques. An interesting application of such a
      concept would be to generate contrast in tissue with tissue relaxation times
      modified using exogenous contrast agents. An amplitude-modulated adiabatic
      waveform has been shown in the past to perform spin-lock MRI. However,
      implementation of this waveform may not prove to be efficient and practical in
      research or a clinical setup due to high radiofrequency power deposition. Recent
      advancement in software and hardware MR technology allows implementation of
      amplitude- and phase-modulated adiabatic waveforms on MR systems. The aim of this
      work was to explore role of adiabatic waveforms in performing rho imaging and
      demonstrate that amplitude- and phase-modulated waveforms [e.g., hyperbolic
      secant, B1 independent rotation-4 (BIR-4) waveforms] can be used to distinguish
      materials that differ in T1/T2 ratio. METHODS AND RESULTS: MR simulation was
      performed using computer routines implemented in MATLAB environment (Mathworks,
      Natick, MA). Modified Bloch equations with trapezoidal, hyperbolic secant and BIR
      4 waveforms were used to perform MR simulation. Trapezoidal waveforms were only
      used for comparison to other waveforms. Gadolinium DTPA (Gad-DTPA) (T1/T2
      approximately 1) and manganese chloride (MnCl(2)) (T1/T2 approximately 10) were
      used as examples of contrast agents due to their routine use in clinical and
      research setups and more importantly because they provide good examples of
      materials differing in T1/T2 ratios. Results of spin locking using trapezoidal
      waveform agree very well with the previously published results, thereby
      validating the computer routines used in this MR simulation. Plots of M(rho)
      (magnetization vector in rho domain) vs. offset frequency show distinct curves
      for these materials differing in T1/T2 for the three waveforms. BIR-4 waveform
      demonstrated a 40% difference in M(rho) ( approximately 150 Hz) for the
      materials. Rate of spin lock with hyperbolic secant waveform was rapid compared
      to other waveforms. DISCUSSION: MR simulation using contrast agents Gad-DTPA and
      MnCl(2) provided a useful way to demonstrate that amplitude- and phase-modulated
      adiabatic waveforms can be used to perform spin-lock imaging. Future work
      involves implementation of these waveforms on MR scanners and performing in vivo
      imaging to generate tissue contrast based on relaxation times ratio.

PMID- 16410179
TI  - Analysis of the distribution of diffusion coefficients in cat brain at 9.4 T
      using the inverse Laplace transformation.
AB  - In this work, the usefulness of the inverse Laplace transformation (ILT) in the
      characterization of diffusion processes in the brain has been investigated. The
      method has been implemented on both phantom and in vivo cat brain data acquired
      at high resolution at 9.4 T. The results were compared with monoexponential and
      biexponential analyses of the same data. It is shown that in the case of
      diffusion restricted by white matter axonal tracts, the resulting diffusograms
      are in good agreement with the biexponential model. In gray matter, however, the
      non-monoexponential decay does not lead to a bimodal distribution in the ILT,
      even though the data can be fitted to a biexponential. This finding suggests the
      possibility of a distribution of diffusion coefficients rather than a discrete
      biexponential behavior. It is shown that this distribution is sensitive, for
      example, to experimental parameters such as the diffusion time. Thus, the ILT
      offers the possibility of implementing a unique tool for the analysis of
      heterogeneous diffusion, that is, the analysis of the diffusion coefficient
      distribution, which has the yet unexplored potential of being a valuable
      parameter in the characterization of tissue structure.

PMID- 16410180
TI  - Spectroscopic imaging of the brain with phased-array coils at 3.0 T.
AB  - The goal of this study was to develop and evaluate high-resolution magnetic
      resonance spectroscopic imaging (MRSI) utilizing the gains in signal-to-noise
      ratio (SNR) provided by combining higher magnetic field with high-sensitivity
      phased-array (PA) coils. We investigated the maximum improvement in spatial
      resolution as small as 0.09 cm(3) for brain MRSI while maintaining adequate SNR
      and acquisition time. The use of low peak power, dual-band spectral-spatial
      pulses was also investigated for application to 3 T MRSI of the brain using the
      body coil for radiofrequency excitation and PA coils for signal reception.

PMID- 16410181
TI  - N-Acetylaspartate concentrations in the thalami of neuropathic pain patients and
      healthy comparison subjects measured with (1)H-MRS.
AB  - We investigated the absolute concentration of N-acetylaspartate (NAA) in the
      thalami of neuropathic pain patients and healthy comparison subjects by single
      voxel proton magnetic resonance spectroscopy ((1)H-MRS). (1)H-MRS was performed
      with a 1.5-T MR system on a voxel in the thalamus bilaterally in 9 neuropathic
      pain patients and 14 healthy control subjects. We measured the absolute
      concentration of NAA using a linear combination model. The NAA concentration in
      the thalamus decreased significantly on the contralateral side in seven patients
      and on the ipsilateral side in two patients, as compared with the mean NAA
      concentration of the healthy control subjects. The NAA concentrations in two
      patients who did not respond to standard pain treatments were extremely
      decreased. Our results using (1)H-MRS suggest that neuropathic pain seems to be
      associated with an abnormal balance of the neural activity in the thalamus. The
      NAA concentration of the thalamus may be related to the efficacy of therapy. (1)H
      MRS may serve as a useful noninvasive tool for evaluating thalamic neural
      activity in neuropathic pain patients.

PMID- 16410182
TI  - Sensitivity enhancement and compensation of RF penetration artifact with planar
      actively detunable quadrature surface coil.
AB  - An actively detunable planar quadrature surface coil for human body imaging at 4
      T has been constructed and compared with a conventional linear surface coil. The
      coil could be used as a transmit/receive or a receive-only device in combination
      with a volume transmit coil. Transmission, reception profiles and the
      corresponding images acquired with each coil, as well as with both individual
      modes of the quadrature coil, are presented. Data collected using a tissue
      equivalent loaded phantom recorded with the linear surface coil demonstrated
      significant intensity distortions due to RF penetration artifact. The quadrature
      surface coil, on the other hand, provided compensation of the artifact,
      separately in its transmission and reception profiles as well as in the resultant
      images. Substantial sensitivity gain was also observed for the quadrature coil
      compared to the linear device. Significant advantages of using the quadrature
      surface coil over the linear device at 4 T have, therefore, been demonstrated.

PMID- 16410183
TI  - NMR relaxometry and imaging of water absorbed in biodegradable polymer scaffolds.
AB  - Porous substrates made of poly(3-hydroxybutyrate-3-hydroxyvalerate) (PHBHV) were
      prepared by a particulate leaching method. After removing the salt by extraction
      in water, proton nuclear magnetic resonance (NMR) relaxometry and imaging were
      performed on sets of PHBHV substrates immersed in phosphate-buffered solution
      during 3 months at different time points. Polarized optical microscopy studies
      were performed on thin sections, 25 and 5 mum, of the PHBHV samples. The results
      of NMR relaxometry showed two (1)H nuclei populations, well distinguishable on
      the free induction decay (FID), due to the different decay time constants, a
      factor of 10(2) apart. Thus, it was possible to separate the two populations,
      giving separate distributions of T(1) relaxation times. One population could be
      associated with water protons in the pores and the other to macromolecular
      protons. The distributions of T(1) and T(2) of the water proton shifted to lower
      values with increasing immersion time to a constant value after 30 days. The
      results obtained by NMR imaging showed an initial increase in the apparent
      porosity, reaching a plateau after 25 days of immersion. This increase is
      attributed mainly to the absorption of water in the microporosity as supported by
      the results of the relaxometry measurements and shown by scanning electron
      microscopy. The average porosity measured by NMR imaging at the plateau, 78+/-3%,
      is slightly higher than that determined by optical microscopy, 73+/-9%, which may
      be due to the fact that the latter method did not resolve the microporosity.
      Overall, the results suggest that at early stages after immersing the scaffolds
      in the aqueous medium, first 30 days approximately, NMR imaging could
      underestimate the porosity of the substrate.

PMID- 16410184
TI  - Optimizing T2-weighted magnetic resonance sequences for surface coil microimaging
      of the eye with regard to lid, eyeball and head moving artifacts.
AB  - PURPOSE: To acquire high-resolution magnetic resonance (MR) images, we developed
      a new blinking artifact reduced pulse (BARP) sequence with a surface coil
      specialized for microscopic imaging (47 mm in diameter). MATERIALS AND METHODS:
      To reduce eye movement, we ascertained that the subjects' eyes were kept open and
      fixated to the target in the 1.5-T MR gantry. To reduce motion artifacts from
      blinking, we inserted rest periods for blinking (1.5 s within every 5 s) during
      MR scanning (T2-weighted fast spin echo; repetition time, 5 s; echo time, 100 ms;
      echo train, 11; matrix, 256 x 128; field of view, 5 cm; 1-mm thickness x 30
      slices). Three scans (100 s x 3) were performed for each normal subject, and they
      were added together after automatic adjustment for location to reduce quality
      loss caused by head motion. RESULTS: T2-weighted MR images were acquired with a
      high resolution and a high signal-to-noise ratio. Motion artifacts were reduced
      with BARP, as compared with those with random blinking. Intraocular structures
      such as the iris and ciliary muscles were clearly visualized. Because the whole
      eye can be covered with a 1-mm thickness by this method, three-dimensional maps
      can easily be generated from the obtained images. CONCLUSION: The application of
      BARP with a surface coil of the human eye might become a useful and widely
      adopted procedure for MR microimaging.

PMID- 16410186
TI  - A pilot evaluation of the use of tissue microarrays for quantitation of target
      distribution in drug discovery pathology.
AB  - The use of tissue microarrays (TMAs) in the determination of novel target
      molecule distribution in organs is an expanding area of discovery pathology. This
      pilot study was carried out to assess the Chromavision automated cellular imaging
      system (ACIS) for quantitation of both mRNA and protein distribution in rat and
      dog TMAs. The targets chosen were a protein kinase, P-CIP2, for mRNA assessment
      and its downsteam target, peptidylglycine amidating monoxygenase (PAM), for
      immunohistochemistry (IHC). Oligonucleotide probes produced against P-CIP2,
      together with an antibody against PAM, were evaluated on rat and dog TMAs. A
      method for evaluation of target distribution using the ACIS was developed and
      involved a two-tier approach. Firstly, an initial scanning of the labelled slides
      identified which tissues expressed the target. Secondly, a more comprehensive
      analysis was made. This required operator interaction to select specific regions
      of interest within selected tissue cores and exclude any background labelling
      from the final assessment. This exacted the level of expression of P-CIP2 or PAM
      in different cellular populations in tissue cores. A comparative semi
      quantitative analysis of the same arrays was concomitantly made by the
      pathologist in order to assess the relative benefits of a potentially time
      consuming detailed morphological evaluation. This involved the histological
      identification by the pathologist of specific cell populations expressing P-CIP2
      or PAM. In this study, we demonstrate the power of an image analysing system to
      provide quantitative data on target distribution by in situ hybridisation and IHC
      on normal TMAs. This methodology, together with detailed histological analysis by
      a pathologist, forms a guideline for future target distribution evaluation within
      discovery pathology.

PMID- 16410187
TI  - Suitability of 5/6 nephrectomy (5/6NX) for the induction of interstitial renal
      fibrosis in rats--influence of sex, strain, and surgical procedure.
AB  - Chronic renal failure (CRF) is a serious clinical problem and currently there are
      no adequate therapeutic strategies for treatment. Many possible treatment
      strategies have been tested in rats with CRF induced by subtotal nephrectomy.
      However, reports in the literature concerning the consequences of this procedure
      on rat kidney function are contradictory. For instance, such an intervention in
      male Sprague-Dawley rats apparently initiates the development of interstitial
      renal fibrosis, while in our similar studies on female Wistar rats (HW) there was
      minimal renal fibrosis. Therefore, we carried out experiments in adult rats to
      investigate the long-term consequences of 5/6 nephrectomy (5/6NX) in relation to
      (1) sex, (2) strain, and (3) two methods of surgical ablation. Ten weeks after
      5/6NX, body weight gain, systolic blood pressure, creatinine clearance, and
      urinary protein were measured, along with renal hydroxyproline concentration
      determinations to assess the deposition of extracellular matrix. Also, light
      microscopic investigations were done to characterize renal damage. The functional
      parameters clearly indicated the development of CRF, while morphologic
      investigations showed only moderate fibrotic areas containing atrophic tubules
      and lymphocytic infiltrates. However, 45-60% of glomeruli were sclerotic. In
      summary, 5/6NX, using either method of partial nephrectomy, induces signs of
      moderate glomerulonephritis preferentially in female HW rats. Thus 5/6NX in
      female HW rats can be recommended as a suitable model in the induction of renal
      fibrosis.

PMID- 16410188
TI  - Cardiac lesions induced by neuroleptic drugs in the rabbit.
AB  - Sudden death seems to be more frequent following treatment with neuroleptic drugs
      in patients with pre-existing cardiac lesions, especially dilated and
      hypertrophic myocardiopathy. The present study was undertaken to confirm the
      hypothesis that myocardial lesions can be induced by neuroleptic drugs. Eight
      groups of 6 New-Zealand White rabbits were treated for 3 months: group I:
      controls (saline); group II: 15 mg/kg/day amisulpride; group III: 0.20 mg/kg/day
      haloperidol; group IV: 3 mg/kg/day levomepromazine; group V: 0.30 mg/kg/day
      olanzapine; group VI: 1.0 mg/kg risperidone, every 15 days; group VII:
      levomepromazine+haloperidol, same dose levels as single treatments; group VIII:
      levomepromazine+risperidone, same dose levels as single treatments. The hearts
      were immediately weighted and fixed, and paraffin sections were prepared and
      examined. Ventricular hypertrophy was observed following treatment with
      olanzapine and was still more marked with the combinations
      levomepromazine+haloperidol and levomepromazine+risperidone. Amisulpride and
      haloperidol induced necrotic lesions and levomepromazine, endocardial fibrosis.
      There was a lack of severe cardiac lesions following treatment with risperidone.
      The observed cardiac lesions can be compared to those seen in toxic myocarditis.
      These findings confirm the hypothesis that some neuroleptic drugs induce
      myocardial lesions. Further studies are warranted to demonstrate the effects of
      treatments of longer duration and the influence of pre-existing cardiac lesions.

PMID- 16410189
TI  - Hsp70 accumulation and ultrastructural features of lung and liver induced by
      ethanol treatment with and without L-carnitine protection in rats.
AB  - This study examined Hsp70 accumulation and the subcellular characteristics of
      liver and lung when exposed to ethanol (EtOH), with and without L-carnitine
      protection. Female Sprague-Dawley rats, 150-200 g body weight, were randomized
      into four groups: Control (CON), Alcohol (ALC), L-carnitine (CAR) and Alcohol-L
      carnitine (ALC-CAR). EtOH was administered per os at a dose of 4 g/kg body weight
      (1 ml) daily for 4 weeks. Before alcohol intake, an oral dose of 500 mg/kg body
      weight of L-carnitine was also administered to the ALC-CAR group. The liver and
      lung samples were subjected to Hsp70 Western blot and ultrastructural analysis.
      The Hsp70 accumulation was higher in the liver than in the lung samples. Hepatic
      Hsp70 accumulation was similar for all groups in contrast to lung, where the
      Hsp70 accumulation depends on the group studied. The ultrastructural results
      showed lung but not liver alterations, evidencing a stressful condition and
      subsequent cellular injury for lung tissue but not for liver. The ALC-CAR group
      showed less lung damage than the non-protected group and resembles the general
      appearance of the CON and CAR groups. EtOH intoxication induced differential
      cellular response in liver and lung in a dose and tissue dependent manner. L
      carnitine seems to reduce lung EtOH-induced subcellular damage. The promotion of
      heat shock or stress proteins might represent one of the mechanisms involved that
      need to be further investigated.

PMID- 16410190
TI  - Paralyzing and myotoxic effects of a recombinant bothropstoxin-I (BthTX-I) on
      mouse neuromuscular preparations.
AB  - As a first step to investigate the structure-function relationship of
      bothropstoxin-I (BthTX-I), a myotoxin from Bothrops jararacussu snake venom, our
      group previously cloned a recombinant toxin (rBthTX-I) in Escherichia coli. The
      aim of this work was to characterize the biological activities of this rBthTX-I
      (1.0 microM) in both phrenic-diaphragm and extensor digitorum longus preparations
      in vitro, by means of myographic and morphologic techniques. Native BthTX-I (1.0
      microM) was used as a standard. The influence of heparin (27.5 microg/ml) upon
      the biological activities of both toxins was also investigated. rBthTX-I had
      similar effects to the native toxin inducing blockage of both directly and
      indirectly evoked contractions in phrenic-diaphragm preparations, and muscle
      damage characterized by edema, round fibers, and cell areas devoid of myofibrils.
      Interestingly the paralyzing activity of rBthTX-I was slightly more potent than
      the native toxin. Heparin prevented paralyzing and myotoxic effects of both the
      native and recombinant toxins. This work shows that rBthTX-I was expressed in a
      fully active form, and presents a biological profile similar to the native toxin.

PMID- 16410191
TI  - Erythropoietic dynamic equilibrium in rats maintained after microwave
      irradiation.
AB  - The aim of study was to define influence of radiofrequency microwave (RF/MW)
      radiation on erythropoiesis in rats. The kinetics of polychromatic erythrocytes
      (PCEs) and micronucleated (MN) PCEs in the bone marrow (BM) and peripheral blood
      (PB) of rats during the intermittent subchronic experiment was followed. Rats
      were exposed 2h/day, 7 days/week to RF/MW of 2.45 GHz and whole-body specific
      absorption rate (SAR) of 1.25+/-0.36 W/kg. Control animals were included in the
      study. Each exposed and control group was killed on the final day of irradiation.
      Acridine-orange stained BM and blood smears were examined by fluorescence
      microscope. PCEs were obtained by inspection of 2000 BM and 1000 PB
      erythrocytes/slides. BMMNs and PBMNs frequency was obtained by observation of
      1000 PCEs/slides. BMPCEs were increased on day 8 and 15, and PBPCEs were elevated
      on days 2 and 8 (p<0.05). The BMMN frequency was increased on experimental day
      15, and MNPCEs in the PB was increased on day 8 (p<0.05). Findings of BM and
      PBPCEs or MNPCEs declined nearly to the control values until the end of the
      experiment. Such findings are considered to be indicators of radiation effects on
      BM erythropoiesis consequently reflected in the PB. Rehabilitated dynamic
      haemopoietc equilibrium in rats by the end of experiment indicates possibility of
      activation adaptation process in rats to the selected experimental conditions of
      subchronic RF/MW exposure.

PMID- 16410192
TI  - Inflammation following stroke.
AB  - Stroke is one of the leading causes of mortality and morbidity. The stroke
      process triggers an inflammatory reaction that may last up to several months.
      Suppression of inflammation using a variety of drugs reduces infarct volume and
      improves clinical outcomes in animal models of stroke. This benefit occurs even
      with the initiation of therapy after 3 hours of onset of stroke, beyond the
      therapeutic window for thrombolysis with tPA. The use of neuroprotectants to
      suppress inflammation may widen the therapeutic time window for tPA while
      lessening its side-effects. Suppression of inflammation may also improve outcomes
      in animal models of haemorrhagic stroke. To date, clinical trials with anti
      inflammatory agents in acute ischaemic stroke have failed to improve clinical
      outcomes. However, because of the potential for broader applicability across all
      aspects of stroke, a better understanding of anti-inflammatory mechanisms is
      important.

PMID- 16410193
TI  - Reading a story.
AB  - Case delineation in clinical medicine is the technique of creating a narrative
      that allows the appropriate scientific knowledge to be brought to bear.
      Neurologists get to be good at this type of story reading and telling from
      dealing with clinical stories which are relatively long and complicated. These
      skills are evident whenever working neurologists gather to discuss case material,
      or when studying their written clinical communications. The purpose of the
      article is to analyze this aspect of everyday neurological practice by looking at
      some of the general principles of story telling and appreciation.

PMID- 16410194
TI  - Posterior cervical decompression and fusion for circumferential spondylotic
      cervical stenosis: review of 50 consecutive cases.
AB  - PURPOSE OF STUDY: This study presents a clinical and radiological evaluation of
      50 consecutive patients with symptomatic spondylotic cervical myelopathy and
      circumferential spinal cord compression who were managed with a single stage wide
      posterior laminectomy and lateral mass instrumented fusion. METHODS USED: 50
      consecutive patients (33 male, 17 female) over a 4 year period presenting with
      symptomatic cervical myelopathy due to circumferential cervical spondylotic
      spinal stenosis were evaluated and operated upon by a single surgeon and followed
      in a prospective fashion. All patients underwent pre- and postoperative clinical,
      radiological and MRI evaluation. SUMMARY OF FINDINGS: No deaths occurred and no
      instrumentation-related neural or vascular injuries were noted. No patient
      required reoperation for ventral compression and in all cases CSF was visible
      anterior to the cord on postoperative MRI scanning, with relief of the
      circumferential compression. Most patients improved by at least 1 Nurick grade.
      Three patients (6%) had single level screw pullouts which did not affect clinical
      outcome, and required no intervention. Slight worsening of kyphosis occurred in
      4% of cases but as group there was no measured difference in sagittal balance
      (P=0.10). Oswestry Neck Disability Scores improved from 25.7+/-3.6 to 16.6+/-7.1
      (P<0.05). One patient required a foraminotomy/posterior discectomy 12 months
      postoperatively at an adjacent level. CONCLUSIONS: This study demonstrates that
      multisegmental spondylotic circumferential cervical stenosis causing symptomatic
      myelopathy can be managed by single stage decompression and fusion via a
      posterior approach with very low morbidity and excellent clinical and
      radiological outcome. The incidence of adjacent segment disease is lower than for
      anterior interbody fusions with a 1%/year incidence at follow up to date.

PMID- 16410195
TI  - Classification of symptomatic osteoporotic compression fractures of the thoracic
      and lumbar spine.
AB  - The pathophysiology of osteoporotic compression fractures is different from those
      occurring secondary to traumatic spinal injury, and currently, there is no
      classification suitable for symptomatic osteoporotic compression fractures
      treated by percutaneous vertebroplasty. We propose a new classification based on
      the radiological appearance in the subacute or chronic stage of the clinical
      presentation of these fractures. They are classified by the authors based on
      observations and measurements from preoperative and postoperative dynamic lateral
      radiographs. Compression fractures are divided into two types. Type I is a
      compression fracture involving the anterior column only. Type II is a fracture
      involving both the anterior and middle column. Each type is divided into two
      groups: fractures with union and those with non-union. Type II compression
      fractures have a higher incidence of non-union than type I (p<0.05). In both type
      I and II non-union groups, fractures achieve greater increase in vertebral body
      height after vertebroplasty than both type I and type II union group fractures
      (p<0.05). In both non-union groups, fractures achieved a greater reduction of
      kyphotic angle post-vertebroplasty than type I and II union group fractures
      (p<0.05). Further clinical follow-up of these patients will confirm and extend
      this classification.

PMID- 16410196
TI  - Carotid atherosclerosis and arterial peripheral pulse wave velocity in cerebral
      thrombosis.
AB  - Stiffening and thickening of the arterial walls are two important components of
      atherosclerosis. A better understanding of the relationship between stiffening
      and thickening of the large arteries might lead to optimal strategies for the
      prevention of cerebrovascular disease. However, there have been few
      investigations of the correlation between carotid artery wall thickening and
      arterial stiffness. In this study, we investigated the relationship between
      arterial stiffness (assessed by the ankle-brachial pulse wave velocity) and
      carotid plaque (detected by high-resolution real-time B-mode ultrasonography) in
      patients with cerebral thrombosis. The subjects were 109 patients with cerebral
      thrombosis aged 40-80 years. Fifty-six subjects had carotid plaque (27 had low
      grade plaques (plaque score<7.0) and 29 had high-grade plaques (plaque score
      >or=7.0)) and 53 subjects did not have plaques. High pulse wave velocity was
      found to be significantly associated with existence of carotid plaque (p<0.001),
      but was not associated with the severity of the plaque (p=0.14) in multivariate
      logistic regression models. This study shows that the pulse wave velocity is
      associated with the existence of carotid atherosclerosis, but not with the
      severity of carotid atherosclerosis, in patients with cerebral thrombosis.

PMID- 16410197
TI  - Image-guided placement of ventricular shunt catheter.
AB  - The position of the ventricular shunt catheter is by far most important factor in
      the long-term patency of a cerebrospinal fluid shunt. However, standard
      technique, which relies on surface anatomic landmarks and the surgeon's sense of
      spatial orientation, is not consistently accurate in the positioning the
      ventricular shunt catheter. Image guidance provides not only a three-dimensional
      reconstruction of the ventricular system, but also a real-time virtual trajectory
      for the catheterization. The authors, using a neuronavigation system, describe
      the ideal trajectory and target for accurate placement of a ventricular shunt
      catheter. Seventeen consecutive trials of image-guided placement of the
      ventricular shunt catheter resulted in excellent positioning of the catheter,
      within the free cerebrospinal fluid space just anterior to the foramen of Monro.
      This positioning was accurate in each case, even if the ventricles were distorted
      or shifted.

PMID- 16410198
TI  - Pattern electroretinography and visual evoked potentials in optic nerve diseases.
AB  - BACKGROUND: To evaluate transient pattern electroretinography (PERG) and pattern
      visual evoked potential (VEP) for the diagnosis, differential diagnosis and
      follow-up of optic nerve diseases. METHODS: Twenty-nine consecutive patients (14
      female, 15 male) with the diagnosis of ischaemic optic neuropathy (n=14) and
      optic neuritis (n=15) were included in this study. Mean age of the patients with
      ischaemic optic neuropathy was 63.3+/-3.3 (60-78) years and the mean age of the
      patients with optic neuritis was 28.3+/-8.4 (19-43) years. In each patient
      ophthalmological examination and systemic evaluation were done and VEP and PERG
      were recorded. As a control group, VEP recordings of 35 healthy subjects were
      included. RESULTS: In the ischaemic optic neuropathy group (group 1), mean VEP
      amplitude (+/-SD) (1.96+/-0.95 microV) was found to be decreased significantly in
      the affected eyes in comparison to the control group and the unaffected eyes. The
      delay in latency (116.3+/-20.14 msec in the affected eyes compared with 101.31+/
      6.19 msec in unaffected eyes) was statistically significant when compared with
      the healthy subjects. In the optic neuritis group (group 2), VEP amplitude was
      decreased (4.13+/-4.04 microV vs 6.97+/-3.35 microV and 6.97+/-4.43 microV) and
      latency was increased (122.59+/-20.09 msec vs 101.31+/-6.19 msec and 108.76+/
      13.57 msec) in affected eyes significantly in comparison to the unaffected eyes
      and control group, respectively. Even though there were no significant
      differences for P50 latency and N95/P50 ratios between affected and unaffected
      eyes in both groups, N95 amplitude decreased significantly in the affected eyes
      of the ischaemic optic neuropathy patients and N95 latency was found to be
      decreased in optic neuritis patients. There was no correlation between VEP and
      PERG findings in both groups. CONCLUSION: VEP amplitude decreased significantly
      in ischaemic optic neuropathies while latency delay was more significant in
      patients with optic neuritis. PERG findings showed decreased N95 amplitude in
      ischemic optic neuropathy without associated latency changes.

PMID- 16410199
TI  - Cerebral cortex: an MRI-based study of volume and variance with age and sex.
AB  - The aim of the present study was to examine quantitative differences in lobar
      cerebral cortical volumes in a healthy adult population. Quantitative volumetric
      MRI of whole brain, cerebral and cerebellar volumes was performed in a cross
      sectional analysis of 97 normal volunteers, with segmented frontal, temporal,
      parietal and occipital cortical volumes measured in a subgroup of 60 subjects, 30
      male and 30 female, matched for age and sex. The right cerebral hemisphere was
      larger than the left across the study group with a small (<1%) but significant
      difference in symmetry (P<0.001). No difference was found between volumes of
      right and left cerebellar hemispheres. Rightward cerebral cortical asymmetry
      (right larger than left) was found to be significant across all lobes except
      parietal. Males had greater cerebral, cerebellar and cerebral cortical lobar
      volumes than females. Larger male cerebral cortical volumes were seen in all
      lobes except for left parietal. Females had greater left parietal to left
      cerebral hemisphere and smaller left temporal to left cerebral hemisphere ratios.
      There was a mild reduction in cerebral volumes with age, more marked in males.
      This study confirms and augments past work indicating underlying structural
      asymmetries in the human brain, and provides further evidence that brain
      structures in humans are differentially sensitive to the effects of both age and
      sex.

PMID- 16410200
TI  - Surgical management of cervical fractures in ankylosing spondylitis using a
      combined posterior-anterior approach.
AB  - The management of cervical fractures in ankylosing spondylitis patients is
      controversial. In the present article, a literature review is conducted, and the
      author's experience with four consecutive cases, operated on using a combined
      approach, is reported. One patient was operated on using the combined approach
      after developing progressive deformity in a halo fixator, one patient after early
      redislocation of an anterior monosegmental fixation, and two patients were
      operated on primarily using the combined approach. All four patients achieved
      good alignment and immediate stability and no dislocation or deformity was
      observed during the mean observation period of 11 months.

PMID- 16410201
TI  - Riluzole therapy for motor neurone disease: an early Australian experience (1996
      2002).
AB  - Riluzole is the only therapy proven in clinical trials to prolong survival in
      patients with motor neurone disease (MND). Prior to its listing by the Australian
      Pharmaceutical Benefits Advisory Scheme in June 2003, the aim of the present
      study was to provide Australian patients with MND early access to riluzole and to
      expand the safety profile data of this therapy. Patients with MND were referred
      to the programme by neurologists covering the Sydney metropolitan region. To be
      eligible to receive riluzole, patients had to be aged between 18 and 75 years and
      have probable or definite MND based on El Escorial criteria, with a disease
      duration of less than 5 years and a vital capacity greater than 60% before study
      entry. Patients were prescribed riluzole 50 mg twice daily. Safety data were
      collected through documentation of adverse events by clinical history in
      combination with regular laboratory screening. Full blood count, haematocrit,
      differential white cell counts and serum liver transaminase levels were obtained
      monthly for 3 months, and then at each 3-monthly visit for 1 year. In total, 25
      patients with MND (17 male, 8 female; age range 40-74 years; mean age 59 years)
      were commenced on riluzole. Of these, 28% had definite MND and the remaining 72%
      were diagnosed as probable MND, with the majority (84%) having limb-onset MND. At
      12 months, 68% of patients continued on riluzole, 16% had died from their disease
      and 16% ceased riluzole because of side-effects or other reasons, largely
      disenchantment owing to a perceived lack of efficacy. Haematological and
      biochemical assays showed no significant alteration during the initial 12-month
      period. Long-term survival data for patients in the present series suggest a
      greater benefit for patients who commenced riluzole early in the course of their
      illness. In conclusion, riluzole was generally tolerated well by Australian
      patients with MND. Of the few patients who experienced side-effects attributed to
      riluzole, all were reversible. Issues related to patient perceptions of efficacy
      highlight the need for patients and treating physicians to maintain realistic
      expectations of riluzole therapy.

PMID- 16410202
TI  - Risk factor management and depression post-stroke: the value of an integrated
      model of care.
AB  - BACKGROUND AND PURPOSE: Shared care initiatives, albeit commonly utilised in
      managing other chronic conditions have not been implemented in the area of stroke
      in Australia. The aims of this project were to adopt a shared care approach for
      stroke survivors comparing an experimental "shared-care" group with a "treatment
      as-usual" control group in reference to the normalization or reversal of vascular
      risk factors and the detection and management of post-stroke depression. METHODS:
      A randomised controlled experimental research design was implemented with
      participants randomized to an intervention or control group and followed over a
      12-month period. The treatment group consisted of a randomly selected group of
      patients, discharged from an acute stroke unit and transferred into the shared
      care model. Risk factors for stroke and depression were compared between the two
      groups. RESULTS: Of 97 patients originally included in the study, 17 dropped out.
      At 12 months, 80 patients remained for analysis (35 in the intervention group and
      45 in the control group). The findings demonstrated positive trends for patients
      within the intervention group that were not found within the control group. The
      percentage of intervention patients reaching target systolic blood pressure (sBP)
      of 140 mmHg after 12 months tended to be greater than in the control group
      (p=0.11, NS). In the intervention group, at 12 months, the total cholesterol
      greater than 5.18 mmol/L was 12.5% compared to 58.8% at discharge. In contrast
      this trend was not so distinct in the control group (57.7% to 42.9%). The
      percentage of patients reaching target (recommended) total cholesterol of 5.18
      mmol/L was significantly greater in the shared care patients intervention group
      relative to the control group (p=0.02). The average number of walks per week was
      also significantly greater in intervention group compared to the control group
      (p=0.048). Moreover, 45% of the control group screened as depressed compared with
      20% of the intervention group at 12 months (p=0.06). CONCLUSIONS: This study
      demonstrates that major risk factors for recurrent stroke and vascular disease in
      general are better managed with the shared care model than with usual post
      discharge care. The significantly reduced depression as found on the screening
      PHQ9 at 12 months indicated that the intervention was beneficial not only in the
      detection of depression but also treatment.

PMID- 16410203
TI  - Differential activation of frontal lobe areas by lexical and semantic language
      tasks: a functional magnetic resonance imaging study.
AB  - To determine whether frontal lobe regions, including Broca's area, dorsolateral
      prefrontal cortex (DLPFC) and supplementary motor area (SMA), are differentially
      activated during lexical and semantic language tasks, we used functional magnetic
      resonance imaging in eight healthy right-handed subjects silently performing two
      semantic tasks (adjective and verb generation) and a lexical retrieval task (noun
      recall). Activation was observed in Broca's area, DLPFC and SMA for all tasks.
      Broca's area activation was approximately doubled during the semantic tasks
      compared with the lexical task (verbs vs nouns: 19.1+/-4.5 vs 8.9+/-1.6 voxels,
      p=0.02; adjectives vs nouns 24.4+/-7.5 vs 10.1+/-2.8 voxels, p=0.04); however,
      there were no significant differences in the DLFPC or SMA across tasks. We
      conclude that Broca's area is more active during tasks that have a semantic
      content, whereas areas involved in preparatory processing (SMA) and memory
      retrieval (DLPFC) are engaged equally during both types of task.

PMID- 16410204
TI  - Quantitation of chromosome 1p and 19q deletions in glial tumours by interphase
      FISH on formalin-fixed paraffin-embedded tissue.
AB  - Deletions on chromosomes 1p and 19q identify oligodendroglial tumours that are
      likely to have a complete response to some chemotherapy regimens and are
      associated with prolonged patient survival. Detection of these chromosomal
      alterations is becoming increasingly important in the evaluation of glial
      tumours. Interphase fluorescence in situ hybridisation (FISH) is one of a number
      of techniques for detecting deletions, and is an efficient method for screening
      large numbers of tumours. We used FISH to detect 1p and 19q deletions in formalin
      fixed paraffin sections of 11 oligodendrogliomas, 11 oligoastrocytomas, two
      astrocytomas and four glioblastomas multiforme. 1p and 19q deletion and non
      deletion ratios were tabulated in 200 nuclei in each tumour. We found
      considerable variation between tumours in the fraction of cells with deletions.
      This variation has not been reported previously and its clinical significance
      will be clarified with patient follow-up. There was little variation between
      regions within the same tumour.

PMID- 16410205
TI  - The case for lamotrigine monitoring in pregnancy.

PMID- 16410206
TI  - Indirect revascularisation for paediatric moyamoya disease: the EDAMS technique.
AB  - Moyamoya disease can have devastating effects on paediatric patients as a result
      of cerebral ischaemia. Several direct and indirect surgical methods have been
      devised in order to facilitate revascularisation. Debate has long ensued about
      which methods are most efficacious and yet safe. The authors describe their
      experience with a straightforward method for performing the EDAMS (encephalo-duro
      arterio-myo-synangiosis) technique.

PMID- 16410207
TI  - Stroke associated with pseudoephedrine in a child with rhabdomyosarcoma.
AB  - Pseudoephedrine is a nasal vasoconstrictor and is contained in many cough and
      cold medications. It is generally harmless when used in recommended doses.
      Hypertensive crisis, psychosis, hemorrhagic stroke, and intracranial hemorrhage
      have been reported as severe complications. We report a 4-year-old girl with
      nasopharyngeal rhabdomyosarcoma who developed stroke while on pseudoephedrine
      therapy for 3 days and had no hematological abnormalities.

PMID- 16410208
TI  - Avascular necroses inducing limb-girdle syndrome.
AB  - Disuse myopathy can be caused by many disorders. However, disuse myopathy with
      symmetrical weakness of the proximal muscles in the four limbs is rare. Here we
      report a 45-year-old man who presented with the appearance of myopathy similar to
      the clinical picture of limb-girdle syndrome with symmetrical weakness of
      proximal muscles in four limbs. A battery of intensive investigations confirmed
      that the patient had symmetric disuse myopathy induced by multiple avascular
      necroses of hip and shoulder joints. After the patient had received bilateral
      total hip replacement operations he had remarkable improvement in his muscle
      power in both lower limbs. This report highlights that some myopathies can be
      reversed if their underlying causes are correctable.

PMID- 16410209
TI  - Rotational vertigo caused by cerebral lesions: vertigo and areas 3av, 2v, and 7.
AB  - We describe two patients complaining of vertigo associated with a small supra
      tentorial convexity meningioma. Symptoms disappeared after tumor removal,
      providing evidence for an association between the vertigo and the cerebral
      cortical lesions. Tumors were located in the central and parietal areas,
      respectively, which are probably analogous to the vestibular cortex in the areas
      designated 3av, 2v, and 7 in animal studies.

PMID- 16410210
TI  - Leptomeningeal carcinomatosis: an unusual cause of sudden onset bilateral
      sensorineural hearing loss.
AB  - We report a 66-year-old woman who developed sudden-onset bilateral sensorineural
      deafness due to leptomeningeal carcinomatosis involving the vestibulocochlear
      nerves. The clinical and diagnostic features of leptomeningeal carcinomatosis are
      discussed.

PMID- 16410211
TI  - Spontaneous cerebrospinal fluid rhinorrhea following excision of a massive
      torcular meningioma.
AB  - A massive supratentorial torcular meningioma was completely resected in a 50-year
      old woman. On the tenth postoperative day she presented with spontaneous
      cerebrospinal fluid (CSF) rhinorrhea. The site of the CSF leak was through the
      region of the cribriform plate, remote from the site of surgery. The possible
      cause of the leak and the relationship with the massive meningioma are analyzed.

PMID- 16410212
TI  - Intracranial multiple myeloma involving the dura.
AB  - Meningeal involvement in multiple myeloma is rare. We report a case in which a
      patient with a history of multiple myeloma presented with neurological deficit
      due to meningeal involvement.

PMID- 16410213
TI  - Traumatic internal carotid artery dissection.
AB  - Traumatic internal carotid artery dissection is a serious condition that may
      cause ischemic stroke in young patients. It has been under-diagnosed in the past.
      We present three cases of traumatic internal carotid artery dissection. The
      clinical manifestations include hemicrania, hemiparesis, partial Horner's
      syndrome and cranial nerve palsy. Diagnosis is with carotid color Doppler
      ultrasound, CT angiography of the neck and conventional angiography. The outcome
      may be poor with hemiparesis, persistent vegetative state and death. We review
      the literature and discuss the clinical presentation, diagnosis, grading and
      treatment choices for traumatic internal carotid artery dissection and stroke.

PMID- 16410214
TI  - Unilateral traumatic posterior fossa subdural effusion in an infant.
AB  - Supratentorial subdural effusion is common after infection and trauma, but rarely
      occurs in the posterior fossa, and is even less commonly unilateral. The authors
      report a rare case of unilateral traumatic posterior fossa subdural effusion with
      secondary hydrocephalus. A 6-month-old female infant presented with lethargy,
      poor appetite, and persistent vomiting after head trauma 2 weeks previously. A
      non-enhanced brain CT scan revealed a right posterior fossa subdural fluid
      collection that displaced the fourth ventricle and brainstem and dilated lateral
      ventricles. While monitoring the intracranial pressure, the baby was treated with
      temporary external subdural drainage, followed by a permanent subdural peritoneal
      shunt. The treatment and likely physiopathology of this unique case are
      discussed.

PMID- 16410215
TI  - Primary lumbar epidermoid tumor mimicking schwannoma.
AB  - A case of a primary lumbar epidermoid tumor is described. Intraspinal epidermoid
      tumors are rare. The differential diagnosis on this case was a nerve sheath
      tumor, such as aschwannoma, as the tumor entered the dural sac and caused dural
      ectasia. The diagnostic pitfalls of this feature of the tumor are discussed.

PMID- 16410217
TI  - Enhancing gliotic cyst wall with microvascular proliferation adjacent to a
      meningioma.
AB  - Cystic meningiomas are uncommon. Contrast enhancement of the cyst wall of
      peritumoral cysts on radiological imaging is generally thought to indicate that
      the wall contains tumor cells. The authors present a patient with a peritumoral
      cyst that enhanced despite the absence of tumor cells. Histological analysis
      demonstrated a gliotic cyst wall with numerous microvascular proliferations
      (MVPs) adjacent to a mixed transitional and angiomatous/microcystic meningioma.
      Immunoreactivity for vascular endothelial growth factor (VEGF) and its receptor,
      flt-1, was observed in the endothelial cells of both intratumoral vessels and
      cyst wall MVPs. Immunoreactivity for tenascin-C was strongly observed within and
      around the vascular wall of MVPs and in gliotic tissue adjacent to the
      meningioma. These changes are unusual in the peritumoral brain parenchyma of a
      slow-growing convexity meningioma and the MVPs may account for the atypical
      contrast enhancement of the cyst wall despite the absence of tumor cells.

PMID- 16410216
TI  - Testosterone improves motor function in Parkinson's disease.
AB  - In Parkinson's disease (PD) there is increasing evidence that sex steroids such
      as estradiol and testosterone modulate, either as a positive or negative effect,
      the clinical expression of a variety of movement disorders involving the
      nigrostriatum. Testosterone deficiency is common in the older male population and
      has an increased prevalence in parkinsonian patients. Testosterone therapy has
      been shown to improve the non-motor symptoms of PD but evidence for a direct
      effect of testosterone on motor symptoms is lacking. This case report
      demonstrates a significant improvement in the resting tremor and fine motor
      control after testosterone administration in a parkinsonian patient with
      testosterone deficiency (1 nmol/L). Motor symptom change was shown by serial
      assessment of the patient's handwriting, self-reporting using the Unified
      Parkinson's Disease Rating Scale and measurement of resting tremor amplitude by
      an accelerometer. The improvement in motor symptoms correlated with serum
      testosterone levels. The use of testosterone replacement in those men with
      decreased levels may improve the motor symptoms as well as increase general
      wellbeing.

PMID- 16410218
TI  - Spinal chondromyxoid fibroma of C2.
AB  - Chondromyxoid fibroma of bone (CMF) is a rare benign primary bone neoplasm
      accounting for less than 0.5% of all primary bone neoplasms. The spine is an
      uncommon site for this tumour, with forty-two cases reported in the modern
      English literature. They have clinical features similar to CMF arising at other
      sites. Local recurrence is well documented. We report an incidentally discovered
      lytic lesion of the C2 vertebra. The patient underwent stereotactic CT guided
      trans-oral curettage of the lesion with iliac bone graft and anterior fusion of
      C2 and C3. Microscopic examination of the surgical specimen demonstrated CMF.
      This is the second reported case of this rare tumour in this location. We review
      the literature and the unique radiological and pathological features and
      management of spinal CMF. Local recurrence of spinal CMF and its management is
      also discussed in light of the five previously reported cases of local spinal
      recurrence.

PMID- 16410219
TI  - Subarachnoid hemorrhage not due to ruptured aneurysm in moyamoya disease.
AB  - A patient with moyamoya disease presenting with subarachnoid hemorrhage (SAH) is
      reported. A 38-year-old Japanese woman developed a sudden onset headache and
      nausea during hospitalization for a cerebral infarct in the right frontal lobe.
      CT scan showed SAH in the left frontal sulci. Cerebral angiogram showed stenosis
      of the distal bilateral internal carotid arteries with moyamoya vessels, and
      significant transdural anastamoses from the left external carotid artery to
      cortical arteries on the left frontal cortex. The patient was kept normotensive
      and underwent a right-sided surgical revascularization procedure, remaining well
      for three years. SAH not due to ruptured aneurysm in moyamoya disease is rare.
      The cause of the SAH was thought to be disruption of the transdural anastomotic
      vessels. Recognition of these fragile vessels in moyamoya disease is essential.

PMID- 16410220
TI  - Methodological studies of multiple reference genes as endogenous controls in
      vascular gene expression studies.
AB  - Detection and quantification of differentially expressed genes requires valid and
      reliable references to control for error variability introduced by preparatory
      procedures or efficiency of reverse transcription and polymerase chain reaction
      (PCR) amplification conditions. So-called housekeeping genes are frequently used
      as endogenous standards, based on the assumption that they are constitutively
      expressed and independent of experimental conditions. However, if the influence
      of experimental stimuli is to be analyzed, it cannot a priori be assumed that
      their expression is unaffected by stimulation. In the present study, the authors
      studied the expression of different housekeeping genes in the vascular
      endothelium of intact conduit vessels perfused in a unique biomechanical
      perfusion model. Ten control gene candidates were investigated by microarray
      expression analysis. Further, five of these genes were systematically analyzed by
      real-time reverse transcriptase (RT)-PCR gene quantification and their
      suitability as reference genes were evaluated. On the basis of these findings,
      the authors suggest criteria for evaluation of endogenous control genes in
      vascular perfusion studies.

PMID- 16410221
TI  - Effect of systemic insulin and angiotensin II receptor subtype-1 antagonist on
      endothelin-1 receptor subtype(s) regulation and binding in diabetic rat heart.
AB  - This study reports on the regulation and remodeling role of endothelin-1 (ET-1)
      and its receptor subtypes, ET(A)-Rs/ET(B)-Rs, at the coronary endothelium (CE)
      and cardiomyocyte (CM) sites. It is carried out in normal and normotensive rats
      with streptozotocin-induced diabetes mellitus receiving different treatment
      modalities. Normal rats were divided into two groups, namely a placebo (N) and a
      losartan-treated (NL), and diabetic rats into four groups receiving placebo (D),
      insulin-treated (DI), losartan-treated (DL), and insulin/losartan-treated (DIL)
      respectively. Binding kinetics of ET-1 to ET(A)-Rs/ET(B)-Rs on CE and CMs were
      assessed in the above groups to try to explain the effect of therapeutic doses of
      an angiotensin II receptor subtype-1 blocker on the dynamics of this ligand and
      its receptor in insulin supplemented diabetic animals. Each group was divided
      into two subgroups: CHAPS-untreated and CHAPS-treated rat hearts perfused with
      [125I]ET-1 to respectively estimate ET-1 binding affinity (tau = 1/k-n) to its
      receptor subtype(s) on CE and CMs using mathematical modeling describing a 1:1
      reversible binding stoichiometry. Heart perfusion results revealed that insulin
      treatment significantly decreased tau on CE but not on CMs in diabetic rats. In
      diabetics treated with losartan, an increase in tau value on CE but not on CMs
      was noted. Cotreatment of diabetic rats with insulin and losartan normalized tau
      on CE but decreased it on CMs. Western blot, using snap-frozen heart tissues,
      revealed increase in ET(A)-R density in all diabetic groups. However, significant
      decrease in ET(B)-R density was observed in all groups compared to the normal,
      and was reconfirmed by immunohistochemical analysis. In conclusion,
      coadministration of insulin and losartan in nonhypertensive animals suffering
      from diabetes type 1 may offer new cardiac protection benefits by improving
      coronary blood flow and cardiomyocyte contractility through modulating ET-1
      receptor subtypes density and affinity at CE and CM sites.

PMID- 16410223
TI  - Endothelial progenitor cells and their potential clinical applications in
      peripheral arterial disease.
AB  - Endothelial progenitor cells (EPCs) were originally thought to be present only
      during embryonic development. New evidence suggests that they can persist into
      adult life, circulate in the peripheral blood and may play an important part in
      endothelial repair and replacement of dysfunctional endothelium. They may also
      play a role in the formation of new blood vessels (angiogenesis, vasculogenesis,
      and arteriogenesis) in ischemic tissues. In addition, EPCs have the potential to
      endothelialize small-diameter prosthetic vascular bypass grafts and generate a
      nonthrombogenic surface, thereby increasing the patency rate of these grafts.
      EPCs may also be used in the clinical assessment of risk of vascular disease. In
      this review, the authors discuss the potential use of EPCs in the management of
      peripheral arterial disease (PAD).

PMID- 16410222
TI  - Atorvastatin affects several angiogenic mediators in human endothelial cells.
AB  - The pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase, have been recently extended to the modulation of
      angiogenesis. Here, to get more insight into the statins action, the authors have
      investigated the effect of atorvastatin on the expression of several angiogenic
      and inflammatory genes in human umbilical endothelial cells (HUVECs).
      Atorvastatin was proangiogenic at the dose of 10 nM, and antiangiogenic at the
      concentrations of 1 to 10 micro M. Moreover, these higher concentrations
      inhibited also the proliferation of HUVECs induced by vascular endothelial growth
      factor (VEGF). Lower doses of atorvastatin did not influence endothelial cell
      proliferation. Importantly, atorvastatin at the micromolar concentrations
      diminished the production of interleukin (IL)-8, a proinflammatory and
      proangiogenic chemokine, and inhibited the synthesis of urokinase plasminogen
      activator (uPA), a potent proinflammatory mediator. However, it decreased also
      the expression of plasminogen activator inhibitor-1 (PAI-1) and thrombospondin-1
      (TSP-1), the inhibitors of angiogenesis. Atorvastatin stimulated the expression
      of angiopoietin (Ang)-2 and moderately enhanced the expression of endothelial
      nitric oxide synthase (eNOS), whereas heme oxygenase-1 (HO-1) was not
      significantly affected. In conclusion, the present findings points to other
      angiogenesis-related effects of atorvastatin, which may be of relevance to the
      beneficial influence of statins in cardiovascular system.

PMID- 16410224
TI  - Endostatin down-regulates soluble guanylate cyclase (sGC) in endothelial cells in
      vivo: influence of endostatin on vascular endothelial growth factor (VEGF)
      signaling.
AB  - Endostatin was suggested to be an antiangiogenic agent with the potential for
      clinical use in cancer therapy. Unfortunately, up to now no antiangiogenic effect
      was seen in clinical trials using this substance. The lack of response might be
      caused by an incomplete understanding of endostatin signaling. Endostatin is
      known to influence the vascular endothelial growth factor (VEGF) signaling
      pathway. It has been reported to bind to the VEGF receptor KDR directly and to
      decrease the phosphorylation of endothelial nitric oxide synthase (eNOS) at
      Ser1177 via the protein phosphatase 2A (PP2A). But so far no details of
      endostatin signaling with regard to NO downstream effectors have been revealed.
      In the present work the authors demonstrate that endostatin down-regulates the
      protein level of soluble guanylate cyclase (sGC) in endothelial cells of newly
      formed blood vessels in 5 day-old wounds (control: 62.5 +/- 33 vessels/mm2,
      endostatin: 9.2 +/- 3.2 vessels/mm2). This was confirmed in experiments with
      endothelial tubes of embryoid bodies and endothelial cells derived from embryonic
      stem cells (eESCs; control: 126 +/- 20, endostatin: 58 +/- 10). The decrease of
      sGC protein levels in response to endostatin was abolished after preincubation
      with the PP2A inhibitor okadaic acid. No alterations of sGC mRNA levels could be
      found under endostatin treatment in eESC. The authors conclude that endostatin
      affects VEGF signaling in endothelial cells by a post-transcriptional PP2A
      dependent down-regulation of sGC protein levels.

PMID- 16410225
TI  - On the role of shear stress in cardiogenesis.
AB  - The relative contribution of physical and chemical factors in organogenesis in
      general and in cardiogenesis in particular is an old and still unsolved question
      in developmental biology (Chang 1932, Anatomical Record, 51, 253-265). A recent
      Nature paper (Hove et al. 2003, Nature, 421, 172-177) strongly suggests (but does
      not prove) the important role of blood flow and associated shear stress in
      cushion tissue morphogenesis. However, another elegantly designed study (Bartman
      et al. 2004, Public Library of Science-Biology, 2, E129) raises questions as to
      the validity of the shear stress hypothesis and the role of physical factors in
      cardiogenesis. Although these studies advance our understanding of cardiac
      development, other possible explanations for the role of blood flow in cardiac
      organogenesis remain to be addressed.

PMID- 16410226
TI  - Sphingosine-1-phosphate-induced intracellular Ca2+ mobilization in human
      endothelial cells.
AB  - The authors have studied the effect of sphingosine-1-phosphate (S1P) on Ca2+
      release from intracellular stores in cultured human umbilical vein endothelial
      cells (HUVECs). In the presence of extracellular Ca2+, S1P increased
      intracellular Ca2+ concentration ([Ca2+]i) and this increase was partially
      inhibited by La3+ (1 microM), indicating that S1P induces Ca2+ influx from
      extracellular pool and Ca2+ release from intracellular stores. S1P increased
      [Ca2+]i concentration dependently in Ca2+-free extracellular solution. The Hill
      coefficient (1.7) and EC50 (420 nM) was obtained from the concentration-response
      relationship. When caffeine depleted Ca2+ store in the presence of ryanodine, S1P
      did not induce intracellular Ca2+ release. Furthermore, the Ca2+-induced Ca2+
      release inhibitors ruthenium red or dantrolene completely inhibited S1P-induced
      intracellular Ca2+ release. S1P-induced intracellular Ca2+ release was inhibited
      by the phospholipase C (PLC) inhibitors neomycin and U73312, or the inositol
      1,4,5-triphosphate (IP3)-gated Ca2+ channel blocker aminoethoxybiphenyl borane (2
      APB). In contrast, S1P-induced intracellular Ca2+ release was not inhibited by
      the mitochondrial Ca2+ uptake inhibitor CCCP or the mitochondrial Ca2+ release
      inhibitor cyclosporin A. These results show that S1P mobilizes Ca2+ from
      intracellular stores primarily via Ca2+-induced and IP3-induced Ca2+ release and
      this Ca2+ mobilization is independent of mitochondrial Ca2+ stores.

PMID- 16410227
TI  - A meta-analysis of the neuropsychological effects of adjuvant chemotherapy
      treatment in women treated for breast cancer.
AB  - Given the improvement in mortality rates associated with breast cancer, the
      importance of understanding the long-term neuropsychological consequences of
      chemotherapy is becoming increasingly vital. This study applies meta-analytic
      techniques to the scant literature on the relationship between contemporary
      adjuvant chemotherapy treatment for breast cancer and cognitive dysfunction as
      examined through neuropsychological indices. Seven studies (involving more than
      300 participants) were selected from over 200 potential articles, based on three
      inclusion criteria: presence of breast cancer, administration of chemotherapy
      treatment, and use of neuropsychological tests. From these, nine treatment
      control comparisons were used to generate 129 Hedge's d effect sizes across the
      cognitive domains of simple attention, working memory short- and long-term
      memory, speed of processing, language, spatial abilities, and motor function.
      Small to medium cumulative effect sizes, showing diminished cognitive function
      for chemotherapy treatment groups compared to control groups, were obtained for
      each of the eight cognitive domains. Overall, these results suggest that women
      who undergo adjuvant chemotherapy as treatment for breast cancer may experience
      subtle yet consequential cognitive decline.

PMID- 16410228
TI  - Apnea diving: long-term neurocognitive sequelae of repeated hypoxemia.
AB  - This article examines the neurocognitive sequelae of repeated exposure to
      hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the
      physiological and neurological adaptations involved in the "human diving reflex"
      is presented. The results from a neuropsychological investigation of N = 21 elite
      apnea divers are evaluated. Standard neuropsychological tests, with known
      sensitivity to mild brain insults, included speed of visuo-motor responding,
      speed of language comprehension, response inhibition, and visual and verbal
      attention and recall tasks. Results indicated that the breath-hold divers
      performed tasks within the average range compared to norms on all tests,
      suggesting that 1-20 years of repeated exposure to hypoxemia including multiple
      adverse neurological events did not impact on performance on standard
      neuropsychological tasks. The results are discussed in relation to implications
      for clinical conditions such as sleep apnea, respiratory disorders, altitude
      sickness, and recreational apnea activities.

PMID- 16410230
TI  - A system for ultrasound-guided computer-assisted orthopaedic surgery.
AB  - Current computer-assisted orthopedic surgery (CAOS) systems typically use
      preoperative computed tomography (CT) and intraoperative fluoroscopy as their
      imaging modalities. Because these imaging tools use X-rays, both patients and
      surgeons are exposed to ionizing radiation that may cause long-term health
      damage. To register the patient with the preoperative surgical plan, these
      techniques require tracking of the targeted anatomy by invasively mounting a
      tracking device on the patient, which results in extra pain and may prolong
      recovery time. The mounting procedure also leads to a major difficulty of using
      these approaches to track small bones or mobile fractures. Furthermore, it is
      practically impossible to mount a heavy tracking device on a small bone, which
      thus restricts the use of CAOS techniques. This article presents a novel CAOS
      method that employs 2D ultrasound (US) as the imaging modality. Medical US is non
      ionizing and real-time, and our proposed method does not require any invasive
      mounting procedures. Experiments have shown that the proposed registration
      technique has sub-millimetric accuracy in localizing the best match between the
      intraoperative and preoperative images, demonstrating great potential for
      orthopedic applications. This method has some significant advantages over
      previously reported US-guided CAOS techniques: it requires no segmentation and
      employs only a few US images to accurately and robustly localize the patient.
      Preliminary laboratory results on both a radius-bone phantom and human subjects
      are presented.

PMID- 16410231
TI  - A comparison study assessing the feasibility of ultrasound-initialized deformable
      bone models.
AB  - This article presents a feasibility and evaluation study for using 2D ultrasound
      in conjunction with our statistical deformable bone model within the scope of
      computer-assisted surgery. The final aim is to provide the surgeon with enhanced
      3D visualization for surgical navigation in orthopedic surgery without the need
      for preoperative CT or MRI scans. We unified our earlier work to combine several
      automatic methods for statistical bone shape prediction and ultrasound
      segmentation and calibration to provide the intended rapid and accurate
      visualization. We compared the use of a tracked digitizing pointer and ultrasound
      for acquiring landmarks and bone surface points for the estimation of two cast
      proximal femurs.

PMID- 16410232
TI  - BoneMorphing versus freehand localization of anatomical landmarks: consequences
      for the reproducibility of implant positioning in total knee arthroplasty.
AB  - OBJECTIVE: This study analyzed the influence of the acquisition method in image
      free computer-assisted total knee arthroplasty (CAS-TKA), and the reproducibility
      of implant planning using BoneMorphing, a 3D morphometric model obtained by a 3D
      to-3D elastic registration of statistical models to sparse point clouds acquired
      directly on the bone surface with a pointer. MATERIALS AND METHODS: Five surgeons
      (one expert, four trainees) each performed a CAS-TKA hybrid protocol based on
      morphometric models and landmarks on a cadaveric knee 10 times. In addition,
      several additional landmarks were digitized during each acquisition. The
      reproducibility of the implant positioning and sizing, as determined by an
      implant planning algorithm with morphometric models, was compared to direct
      digitization accuracy. RESULTS: Femoral and tibial implant positioning parameters
      with the hybrid protocol resulted in intra-surgeon standard deviations (SDs) of
      less than+/-1.4 degrees for rotation and 1.9 mm for translation for all surgeons
      in all directions except for tibial axial rotation (the only parameter determined
      by a digitized landmark and not recomputed in the 3D model). The variability in
      individual landmark digitization varied from 2 to 5 mm SD for certain landmarks,
      with ranges of 15-25 mm across all surgeons. The comparison study showed an
      improvement in femoral rotation reproducibility with the morphometric model when
      using the posterior condylar axis. Tibial implant reproducibility for each method
      was comparable, with the morphometric model giving better results in well
      digitized areas such as the tibial plateau. CONCLUSION: A CAS-TKA protocol based
      on a deformed statistical model offers reproducible implant positioning. Some
      landmarks, such as distal condyles, show sufficient reproducibility in the
      direction of interest, while others, such as the anterior tibial tubercle, can
      lead to hazardous implant positioning. This should be taken into consideration
      when designing a CAS-TKA system with bony landmarks. In areas where a sufficient
      number of points have been digitized with good coverage, such as on the distal
      and posterior femoral condyles or the tibial plateau areas, the information
      derived from the 3D model is more accurate and reproducible than that derived
      from digitization. Good training and a guiding user interface are essential to
      guarantee coverage quality.

PMID- 16410233
TI  - New orthopaedic implant management tool for computer-assisted planning,
      navigation, and simulation: from implant CAD files to a standardized XML-based
      implant database.
AB  - Computer-Assisted Orthopaedic Surgery (CAOS) has made much progress over the last
      10 years. Navigation systems have been recognized as important tools that help
      surgeons, and various such systems have been developed. A disadvantage of these
      systems is that they use non-standard formalisms and techniques. As a result,
      there are no standard concepts for implant and tool management or data formats to
      store information for use in 3D planning and navigation. We addressed these
      limitations and developed a practical and generic solution that offers benefits
      for surgeons, implant manufacturers, and CAS application developers. We developed
      a virtual implant database containing geometrical as well as calibration
      information for orthopedic implants and instruments, with a focus on trauma. This
      database has been successfully tested for various applications in the
      client/server mode. The implant information is not static, however, because
      manufacturers periodically revise their implants, resulting in the deletion of
      some implants and the introduction of new ones. Tracking these continuous changes
      and keeping CAS systems up to date is a tedious task if done manually. This leads
      to additional costs for system development, and some errors are inevitably
      generated due to the huge amount of information that has to be processed. To ease
      management with respect to implant life cycle, we developed a tool to assist end
      users (surgeons, hospitals, CAS system providers, and implant manufacturers) in
      managing their implants. Our system can be used for pre-operative planning and
      intra-operative navigation, and also for any surgical simulation involving
      orthopedic implants. Currently, this tool allows addition of new implants,
      modification of existing ones, deletion of obsolete implants, export of a given
      implant, and also creation of backups. Our implant management system has been
      successfully tested in the laboratory with very promising results. It makes it
      possible to fill the current gap that exists between the CAS system and implant
      manufacturers, hospitals, and surgeons.

PMID- 16410234
TI  - Accuracy of acetabular component positioning with a fluoroscopically referenced
      CAOS system.
AB  - OBJECTIVE: This study evaluated the accuracy, repeatability, and reproducibility
      of a fluoroscopic referenced system used for guiding acetabular component
      positioning. METHODS: Calibration of the Medtronic StealthStation Treon Plus
      system was performed using a Weber gage block to assess linearity. Metrologic
      validation of repeatability and reproducibility was done using a cadaveric pelvis
      with an uncemented cup placed in the target position of 45 degrees inclination
      and 17.5 degrees anteversion. A baseline assessment was done with a National
      Institute of Standards and Technology (NIST) traceable coordinate measuring
      machine (CMM). RESULTS: Weber gage block analysis revealed a mean bias of 0.69
      mm. For the cadaveric pelvis, the anterior pelvic plane was determined using the
      bilateral anterior superior iliac spines with the symphysis pubis as the inferior
      landmark. The mean CMM measurement was inclination of 46.023 degrees (SD=1.075;
      range: 43.318-46.844 degrees) and anteversion of 15.787 degrees (SD=0.411; range:
      15.068-16.384 degrees). One surgeon performed a repeatability assessment (n=8),
      finding mean inclination of 42.8 degrees (SD=1.5; range: 39.5-44.5 degrees) and
      anteversion of 17.5 degrees (SD=3.0; range: 14.5-22.5 degrees). Three surgeons
      performed a reproducibility assessment (n=24), finding mean overall inclination
      of 48.5 degrees (SD=0.9; range: 46-50 degrees) and anteversion of 17.8 degrees
      (SD=2.5; range: 13.5-23.5 degrees). All measurements were within a predefined
      acceptability range of+/-5 degrees. DISCUSSION: The accuracy and reproducibility
      of the fluoroscopic referencing method was found to be suitable for determination
      of cup position in the surgical setting. Anteversion measurements were more
      variable for the fluoroscopic method and this may be related to the difficulty
      for the surgeon in predictably picking the anatomical points from the
      fluoroscopic image.

PMID- 16410235
TI  - Accuracy and potential pitfalls of fluoroscopy-guided acetabular cup placement.
AB  - Using a total of 30 cadaveric hips, the accuracy of a fluoroscopy-based computer
      navigation system for cup placement in total hip arthroplasty (THA) was
      investigated and an error analysis was carried out. The accuracy of placing the
      acetabular component within a predefined safe zone using computer guidance was
      compared to the precision that could be achieved with a freehand approach.
      Accurate control measurements of the implanted cup were obtained using fiducial
      based matching to a pre-operative CT scan with respect to the anterior pelvic
      plane. A significantly higher number of cups were placed in the safe zone with
      the help of the navigation system. The variability of cup placement could be
      reduced for cup abduction but not substantially for cup version. An error
      analysis of inaccurate landmark reconstruction revealed that the registration of
      the mid-pubic point with fluoroscopy was a potential source of error. Keeping
      this pitfall in mind, fluoroscopy-based navigation in THA is a useful tool for
      registration of the pelvic coordinate system, particularly those points that
      cannot be reached by direct pointer digitization with the patient in the lateral
      decubitus position.

PMID- 16410236
TI  - Computer-assisted femoral head resurfacing.
AB  - Femoral head resurfacing is re-emerging as a surgical option for younger patients
      who are not yet candidates for total hip replacement. However, this procedure is
      more difficult than total hip replacement, and the mechanical jigs typically used
      to align the implant produce significant variability in implant placement and
      take a significant amount of time to position properly. We propose that a
      computer-assisted surgical (CAS) technique could reduce implant variability with
      little or no increase in operative time. We describe a new CAS technique for this
      procedure and demonstrate in a cadaver study of five paired femurs that the CAS
      technique in the hands of a novice surgeon markedly reduced the varus/valgus
      variability of the implant relative to the pre-operative plan (2 degrees standard
      deviation for CAS versus 5 degrees for a mechanical jig operated by an expert
      surgeon). We also show that the mechanical jig resulted in significantly
      retroverted implant placement. There was no significant difference in operative
      time between the two techniques.

PMID- 16410237
TI  - Computer-assisted optimization of correction osteotomies on lower extremities.
AB  - Automated methods are presented for the planning of correction osteotomies and
      osteosynthesis on lower extremities. Intraoperative calibrated X-ray images and
      kinematic measurements using optical tracking systems are the basis for the
      identification of the individual anatomy of the patient. The correction input of
      the surgeon, together with optimization algorithms, allows the calculation of the
      position and orientation of the osteotomies and the repositioning of the bone
      fragments. A navigation module supports the surgeon during the execution of
      osteotomies and repositioning, as well as osteosynthesis. So far, the approach
      has been evaluated in laboratory trials and ex vivo tests.

PMID- 16410238
TI  - Endoscope-based hybrid navigation system for minimally invasive ventral spine
      surgeries.
AB  - The availability of high-resolution, magnified, and relatively noise-free
      endoscopic images in a small workspace, 4-10 cm from the endoscope tip, opens up
      the possibility of using the endoscope as a tracking tool. We are developing a
      hybrid navigation system in which image-analysis-based 2D-3D tracking is combined
      with optoelectronic tracking (Optotrak) for computer-assisted navigation in
      laparoscopic ventral spine surgeries. Initial results are encouraging and confirm
      the ability of the endoscope to serve as a tracking tool in surgical navigation
      where sub-millimetric accuracy is mandatory.

PMID- 16410239
TI  - The effects of the phenylalanine 256 to valine mutation on the sensitivity of
      sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) Ca2+ pump isoforms 1, 2,
      and 3 to thapsigargin and other inhibitors.
AB  - Three isoforms of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA)
      are known to exist in mammalian cells. This study investigated the effects of
      thapsigargin and a variety of commonly used hydrophobic inhibitors on these SERCA
      isoforms (i.e. SERCA1b, SERCA2b, and SERCA3a), which were transiently expressed
      in COS-7 cells. In addition, the study assessed whether the introduction of the
      phenylalanine to valine mutation at position 256 (F256V), known to reduce the
      potency of thapsigargin inhibition in avian SERCA1, affects the other SERCA
      isoforms in a similar manner and whether this mutation also affects the
      inhibition by other inhibitors. This study has shown that the sensitivity to
      thapsigargin is different for the SERCA isoforms (apparent K(i) values being
      0.21, 1.3, and 12 nm for SERCA1b, SERCA2b, and SERCA3a, respectively). The
      reduction in thapsigargin sensitivity caused by the F256V mutation was also
      different for the three isoforms, with SERCA2b only being modestly affected by
      this mutation. Although some of the other inhibitors investigated (i.e.
      cyclopiazonic acid and curcumin) showed some differences in their sensitivity
      toward the SERCA isoforms, most were little affected by the F256V mutation,
      indicating that they inhibit the Ca(2+)-ATPase by binding to sites on SERCA
      distinct from that of thapsigargin.

PMID- 16410240
TI  - Medical faculty members at different professorial levels.

PMID- 16410241
TI  - Functions of the cytoplasmic tails of the human receptor activity-modifying
      protein components of calcitonin gene-related peptide and adrenomedullin
      receptors.
AB  - Receptor activity-modifying proteins (RAMPs) enable calcitonin receptor-like
      receptor (CRLR) to function as a calcitonin gene-related peptide receptor
      (CRLR/RAMP1) or an adrenomedullin (AM) receptor (CRLR/RAMP2 or -3). Here we
      investigated the functions of the cytoplasmic C-terminal tails (C-tails) of human
      RAMP1, -2, and -3 (hRAMP1, -2, and -3) by cotransfecting their C-terminal
      deletion or progressive truncation mutants into HEK-293 cells stably expressing
      hCRLR. Deletion of the C-tail from hRAMP1 had little effect on the surface
      expression, function, or intracellular trafficking of the mutant heterodimers. By
      contrast, deletion of the C-tail from hRAMP2 disrupted transport of hCRLR to the
      cell surface, resulting in significant reductions in (125)I-hAM binding and
      evoked cAMP accumulation. The transfection efficiency for the hRAMP2 mutant was
      comparable with that for wild-type hRAMP2; moreover, immunocytochemical analysis
      showed that the mutant hRAMP2 remained within the endoplasmic reticulum. FACS
      analysis revealed that deleting the C-tail from hRAMP3 markedly enhances AM
      evoked internalization of the mutant heterodimers, although there was no change
      in agonist affinity. Truncating the C-tails by removing the six C-terminal amino
      acids of hRAMP2 and -3 or exchanging their C-tails with one another had no effect
      on surface expression, agonist affinity, or internalization of hCRLR, which
      suggests that the highly conserved Ser-Lys sequence within hRAMP C-tails is
      involved in cellular trafficking of the two AM receptors. Notably, deleting the
      respective C-tails from hRAMPs had no effect on lysosomal sorting of hCRLR. Thus,
      the respective C-tails of hRAMP2 and -3 differentially affect hCRLR surface
      delivery and internalization.

PMID- 16410242
TI  - Rotenone-like action of the branched-chain phytanic acid induces oxidative stress
      in mitochondria.
AB  - Phytanic acid (Phyt) increase is associated with the hereditary neurodegenerative
      Refsum disease. To elucidate the still unclear toxicity of Phyt, mitochondria
      from brain and heart of adult rats were exposed to free Phyt. Phyt at low
      micromolar concentrations (maximally: 100 nmol/mg of protein) enhances superoxide
      (O(2)(.))(2) generation. Phyt induces O(2)(.) in state 3 (phosphorylating), as
      well as in state 4 (resting). Phyt stimulates O(2)(.) generation when the
      respiratory chain is fed with electrons derived from oxidation of
      glutamate/malate, pyruvate/malate, or succinate in the presence of rotenone. With
      succinate alone, Phyt suppresses O(2)(.) generation caused by reverse electron
      transport from succinate to complex I. The enhanced O(2)(.) generation by Phyt in
      state 4 is in contrast to the mild uncoupling concept. In this concept uncoupling
      by nonesterified fatty acids should abolish O(2)(.) generation. Stimulation of
      O(2)(.) generation by Phyt is paralleled by inhibition of the electron transport
      within the respiratory chain or electron leakage from the respiratory chain. The
      interference of Phyt with the electron transport was demonstrated by inhibition
      of state 3- and p-trifluoromethoxyphenylhydrazone (FCCP)-dependent respiration,
      inactivation of the NADH-ubiquinone oxidoreductase complex in permeabilized
      mitochondria, decrease in reduction of the synthetic electron acceptor 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide in state 4, and increase of
      the mitochondrial NAD(P)H level in FCCP-uncoupled mitochondria. Thus, we suggest
      that complex I is the main site of Phyt-stimulated O(2)(.) generation.
      Furthermore, inactivation of aconitase and oxidation of the mitochondrial
      glutathione pool show that enhanced O(2)(.) generation with chronic exposure to
      Phyt causes oxidative damage.

PMID- 16410243
TI  - Vangl1 protein acts as a downstream effector of intestinal trefoil factor
      (ITF)/TFF3 signaling and regulates wound healing of intestinal epithelium.
AB  - The intestinal trefoil factor (ITF/TFF3) protects intestinal epithelia from a
      range of insults and contributes to mucosal repair. However, the signaling events
      that mediate healing responses are only partially understood. To identify ITF
      signaling pathways, proteins that were Ser/Thr phosphorylated in response to ITF
      stimulation were immunoprecipitated from human colon carcinoma cell lines and
      identified by mass spectrometry. We demonstrated that Van Gogh-like protein 1
      (also designated Vang-like 1 or Vangl1), a protein with four transmembrane
      domains, was Ser/Thr phosphorylated in response to ITF stimulation. Vangl1 was
      present in normal human colon and all intestinal epithelial cell lines (IEC)
      tested. In transfected IEC, FLAG-Vangl1 was mostly present in the Nonidet P-40
      soluble fraction as detected by Western blotting, corresponding to the
      localization of endogenous protein in cytoplasmic vesicular structures by
      confocal microscopy with rabbit polyclonal anti-human Vangl1 antibody (alpha
      Vangl1). Vangl1 cell membrane association increased with differentiation, as
      demonstrated by co-localization with E-cadherin in differentiated IEC. Increased
      Vangl1 phosphorylation after stimulation with ITF corresponded to decreased cell
      membrane association with E-cadherin. Functionally, Vangl1 overexpression
      enhanced ITF unstimulated and stimulated wound closure of IEC, whereas siRNA
      directed against Vangl1 inhibited the migratory response to ITF. Vangl1 protein
      may serve as an effector mediating the ITF healing response of the intestinal
      mucosa.

PMID- 16410244
TI  - Hyposecretion, not hyperabsorption, is the basic defect of cystic fibrosis airway
      glands.
AB  - Human airways and glands express the anion channel cystic fibrosis transmembrane
      conductance regulator, CFTR, and the epithelial Na(+) channel, ENaC. Cystic
      fibrosis (CF) airway glands fail to secrete mucus in response to vasoactive
      intestinal peptide or forskolin; the failure was attributed to loss of CFTR
      mediated anion and fluid secretion. Alternatively, CF glands might secrete acinar
      fluid via CFTR-independent pathways, but the exit of mucus from the glands could
      be blocked by hyperabsorption of fluid in the gland ducts. This could occur
      because CFTR loss can disinhibit ENaC, and ENaC activity can drive absorption. To
      test these two hypotheses, we measured single gland mucus secretion optically and
      applied ENaC inhibitors to determine whether they augmented secretion. Human CF
      glands were pretreated with benzamil and then stimulated with forskolin in the
      continued presence of benzamil. Benzamil did not rescue the lack of secretion to
      forskolin (50 glands, 6 CF subjects) nor did it increase the rate of
      cholinergically mediated mucus secretion from CF glands. Finally, neither
      benzamil nor amiloride increased forskolin-stimulated mucus secretion from
      porcine submucosal glands (75 glands, 7 pigs). One possible explanation for these
      results is that ENaC within the gland ducts was not active in our experiments.
      Consistent with that possibility, we discovered that human airway glands express
      Kunitz-type and non-Kunitz serine protease inhibitors, which might prevent
      proteolytic activation of ENaC. Our results suggest that CF glands do not display
      excessive, ENaC-mediated fluid absorption, leaving defective, anion-mediated
      fluid secretion as the most likely mechanism for defective mucus secretion from
      CF glands.

PMID- 16410246
TI  - The molecular mechanism of peptide-mediated erythromycin resistance.
AB  - The macrolide antibiotic erythromycin binds at the entrance of the nascent
      peptide exit tunnel of the large ribosomal subunit and blocks synthesis of
      peptides longer than between six and eight amino acids. Expression of a short
      open reading frame in 23 S rRNA encoding five amino acids confers resistance to
      erythromycin by a mechanism that depends strongly on both the sequence and the
      length of the peptide. In this work we have used a cell-free system for protein
      synthesis with components of high purity to clarify the molecular basis of the
      mechanism. We have found that the nascent resistance peptide interacts with
      erythromycin and destabilizes its interaction with 23 S rRNA. It is, however, in
      the termination step when the pentapeptide is removed from the peptidyl-tRNA by a
      class 1 release factor that erythromycin is ejected from the ribosome with high
      probability. Synthesis of a hexa- or heptapeptide with the same five N-terminal
      amino acids neither leads to ejection of erythromycin nor to drug resistance. We
      propose a structural model for the resistance mechanism, which is supported by
      docking studies. The rate constants obtained from our biochemical experiments are
      also used to predict the degree of erythromycin resistance conferred by varying
      levels of resistance peptide expression in living Escherichia coli cells
      subjected to varying concentrations of erythromycin. These model predictions are
      compared with experimental observations from growing bacterial cultures, and
      excellent agreement is found between theoretical prediction and experimental
      observation.

PMID- 16410245
TI  - Activation of Bak and Bax through c-abl-protein kinase Cdelta-p38 MAPK signaling
      in response to ionizing radiation in human non-small cell lung cancer cells.
AB  - Intracellular signaling molecules and apoptotic factors seem to play an important
      role in determining the radiation response of tumor cells. However, the basis for
      the link between signaling pathway and apoptotic cell death machinery after
      ionizing irradiation remains still largely unclear. In this study, we showed that
      c-Abl-PKCdelta-Rac1-p38 MAPK signaling is required for the conformational changes
      of Bak and Bax during ionizing radiation-induced apoptotic cell death in human
      non-small cell lung cancer cells. Ionizing radiation induced conformational
      changes and subsequent oligomerizations of Bak and Bax, dissipation of
      mitochondrial membrane potential, and cytochrome c release from mitochondria.
      Small interference (siRNA) targeting of Bak and Bax effectively protected cells
      from radiation-induced mitochondrial membrane potential loss and apoptotic cell
      death. p38 MAPK was found to be selectively activated in response to radiation
      treatment. Inhibition of p38 MAPK completely suppressed radiation-induced Bak and
      Bax activations, dissipation of mitochondrial membrane potential, and cell death.
      Moreover, expression of a dominant negative form of protein kinase Cdelta
      (PKCdelta) or siRNA targeting of PKCdelta attenuated p38 MAPK activation and
      conformational changes of Bak and Bax. In addition, ectopic expression of RacN17,
      a dominant negative form of Rac1, markedly inhibited p38 MAPK activation but did
      not affect PKCdelta activation. Upon stimulation of cells with radiation,
      PKCdelta was phosphorylated dramatically on tyrosine. c-Abl-PKCdelta complex
      formation was also increased in response to radiation. Moreover, siRNA targeting
      of c-Abl attenuated radiation-induced PKCdelta and p38 MAPK activations, and Bak
      and Bax modulations. These data support a notion that activation of the c-Abl
      PKCdelta-Rac1-p38 MAPK pathway in response to ionizing radiation signals
      conformational changes of Bak and Bax, resulting in mitochondrial activation
      mediated apoptotic cell death in human non-small cell lung cancer cells.

PMID- 16410247
TI  - Role of the carbohydrate binding site of the Streptococcus pneumoniae capsular
      polysaccharide type 3 synthase in the transition from oligosaccharide to
      polysaccharide synthesis.
AB  - The type 3 synthase catalyzes the formation of the Streptococcus pneumoniae type
      3 capsular polysaccharide [-3)-beta-D-GlcUA-(1, 4)-beta-D-Glc-(1-]n. Synthesis is
      comprised of two distinct catalytic phases separated by a transition step whereby
      an oligosaccharylphosphatidylglycerol primer becomes tightly bound to the
      carbohydrate acceptor recognition site of the synthase. Using the recombinant
      synthase in Escherichia coli membranes, we determined that a critical
      oligosaccharide length of approximately 8 monosaccharides was required for
      recognition of the growing chain by the synthase. Upon binding of the
      oligosaccharide-lipid to the carbohydrate recognition site, the polymerization
      reaction entered a highly processive phase to produce polymer of high molecular
      weight. The initial oligosaccharide-synthetic phase also appeared to be
      processive, the duration of which was enhanced by the concentration of UDP-GlcUA
      and diminished by an increase in temperature. The overall reaction approached a
      steady state equilibrium between the polymer- and oligosaccharide-forming phases
      that was shifted toward the former by higher UDP-GlcUA levels or lower
      temperatures and toward the latter by lower concentrations of UDP-GlcUA or higher
      temperatures. The transition step between the two enzymatic phases demonstrated
      cooperative kinetics, which is predicted to reflect a possible reorientation of
      the oligosaccharide-lipid in conjunction with the formation of a tight binding
      complex.

PMID- 16410249
TI  - Endogenously bound calmodulin is essential for the function of the inositol 1,4,5
      trisphosphate receptor.
AB  - Calmodulin (CaM) is a ubiquitous Ca2+ sensor protein that plays an important role
      in regulating a large number of Ca2+ channels, including the inositol 1,4,5
      trisphosphate receptor (IP3R). Despite many efforts, the exact mechanism by which
      CaM regulates the IP3R still remains elusive. Here we show, using unidirectional
      45Ca2+ flux experiments on permeabilized L15 fibroblasts and COS-1 cells, that
      endogenously bound CaM is essential for the proper activation of the IP3R.
      Removing endogenously bound CaM by titration with a high affinity (pM) CaM
      binding peptide derived from smooth muscle myosin light-chain kinase (MLCK
      peptide) strongly inhibited IP3-induced Ca2+ release. This inhibition was
      concentration- and time-dependent. Removing endogenously bound CaM affected the
      maximum release capacity but not its sensitivity to IP3. A mutant peptide with a
      strongly reduced affinity for CaM did not affect inhibited IP3-induced Ca2+
      release. Furthermore, the inhibition by the MLCK peptide was fully reversible. Re
      adding exogenous CaM, but not CaM1234, reactivated the IP3R. These data suggest
      that, by using a specific CaM-binding peptide, we removed endogenously bound CaM
      from a high affinity CaM-binding site on the IP3R, and this resulted in a
      complete loss of the IP3R activity. Our data support a new model whereby CaM is
      constitutively associated with the IP3R and functions as an essential subunit for
      proper functioning of the IP3R.

PMID- 16410248
TI  - Selective inhibition of fibroblast activation protein protease based on dipeptide
      substrate specificity.
AB  - Fibroblast activation protein (FAP) is a transmembrane serine peptidase that
      belongs to the prolyl peptidase family. FAP has been implicated in cancer;
      however, its specific role remains elusive because inhibitors that distinguish
      FAP from other prolyl peptidases like dipeptidyl peptidase-4 (DPP-4) have not
      been developed. To identify peptide motifs for FAP-selective inhibitor design, we
      used P(2)-Pro(1) and acetyl (Ac)-P(2)-Pro(1) dipeptide substrate libraries, where
      P(2) was varied and substrate hydrolysis occurs between Pro(1) and a fluorescent
      leaving group. With the P(2)-Pro(1) library, FAP preferred Ile, Pro, or Arg at
      the P(2) residue; however, DPP-4 showed broad reactivity against this library,
      precluding selectivity. By contrast, with the Ac-P(2)-Pro(1) library, FAP cleaved
      only Ac-Gly-Pro, whereas DPP-4 showed little reactivity with all substrates. FAP
      also cleaved formyl-, benzyloxycarbonyl-, biotinyl-, and peptidyl-Gly-Pro
      substrates, which DPP-4 cleaved poorly, suggesting an N-acyl-Gly-Pro motif for
      inhibitor design. Therefore, we synthesized and tested the compound Ac-Gly
      prolineboronic acid, which inhibited FAP with a K(i) of 23 +/- 3 nm. This was
      approximately 9- to approximately 5400-fold lower than the K(i) values for other
      prolyl peptidases, including DPP-4, DPP-7, DPP-8, DPP-9, prolyl oligopeptidase,
      and acylpeptide hydrolase. These results identify Ac-Gly-BoroPro as a FAP
      selective inhibitor and suggest that N-acyl-Gly-Pro-based inhibitors will allow
      testing of FAP as a therapeutic target.

PMID- 16410251
TI  - Opposite transcriptional regulation in skeletal muscle of AMP-activated protein
      kinase gamma3 R225Q transgenic versus knock-out mice.
AB  - AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer
      important for metabolic sensing in all eukaryotes. The muscle-specific isoform of
      the regulatory gamma-subunit of the kinase, AMPK gamma3, has an important role in
      glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle,
      as previously demonstrated by physiological characterization of AMPK gamma3
      mutant (R225Q) transgenic (TgPrkag3(225Q)) and gamma3 knock-out (Prkag3(-/-))
      mice. We determined AMPK gamma3-dependent regulation of gene expression by
      analyzing global transcription profiles in glycolytic skeletal muscle from gamma3
      mutant transgenic and knock-out mice using oligonucleotide microarray technology.
      Evidence is provided for coordinated and reciprocal regulation of multiple key
      components in glucose and fat metabolism, as well as skeletal muscle ergogenics
      in TgPrkag3(225Q) and Prkag3(-/-) mice. The differential gene expression profile
      was consistent with the physiological differences between the models, providing a
      molecular mechanism for the observed phenotype. The striking pattern of opposing
      transcriptional changes between TgPrkag3(225Q) and Prkag3(-/-) mice identifies
      differentially expressed targets being truly regulated by AMPK and is consistent
      with the view that R225Q is an activating mutation, in terms of its downstream
      effects. Additionally, we identified a wide array of novel targets and regulatory
      pathways for AMPK in skeletal muscle.

PMID- 16410250
TI  - Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, is
      involved in PAR-2-induced activation of activator protein-1.
AB  - Protease-activated receptor-2 (PAR-2), a G protein-coupled receptor for trypsin
      and tryptase, exerts important physiological and pathological functions in
      multiple systems. However, unlike PAR-1, the PAR-2-mediated intracellular signal
      transductions are hardly known. Here, using yeast two-hybrid screening with a
      human brain cDNA library, we identified an interacting partner of human PAR-2,
      the Jun activation domain-binding protein 1 (Jab1). The interaction was confirmed
      by glutathione S-transferase pull-down assays in vitro, and by co
      immunoprecipitation assays in vivo. Jab1 was also shown to be colocalized with
      PAR-2 in both transfected HEK293 cells and in normal primary human astrocytes by
      double immunofluorescence staining. Further experiments demonstrated that
      multiple intracellular domains of PAR-2 are required for the interaction with
      Jab1. We then showed that agonist stimulation of PAR-2 disrupted the interaction,
      which could be prevented by the inhibitor of receptor endocytosis phenylarsine
      oxide, but not by the lysosomal protease inhibitor ZPAD. Importantly, we found
      that activation of PAR-2 induced the redistribution of Jab1 from the plasma
      membrane to the cytosol, but did not influence expression of Jab1. Furthermore,
      Jab1 mediated PAR-2-induced c-Jun activation, which was followed by increased
      activation of activator protein-1. Loss-of-function studies, using Jab1 small
      interfering RNA, demonstrated that Jab1 knockdown blocked PAR-2-induced activator
      protein-1 activation. Taken together, our data demonstrate that Jab1 is an
      important effector that mediates a novel signal transduction pathway for PAR-2
      dependent gene expression.

PMID- 16410252
TI  - Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I
      leading to mitochondrial failure.
AB  - This study evaluated the action of tamoxifen and estradiol on the function of
      isolated liver mitochondria. We observed that although tamoxifen and estradiol
      per se did not affect mitochondrial complexes II, III, or IV, complex I is
      affected, this effect being more drastic (except for state 4 of respiration) when
      mitochondria were coincubated with both drugs. Furthermore, using two respiratory
      chain inhibitors, rotenone and diphenyliodonium chloride, we identified the
      flavin mononucleotide site of complex I as the target of tamoxifen and/or
      estradiol action(s). Tamoxifen (25 microm) per se induced a significant increase
      in hydrogen peroxide production and state 4 of respiration. Additionally, a
      significant decrease in respiratory control ratio, transmembrane, and
      depolarization potentials were observed. Estradiol per se decreased carbonyl
      cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated respiration, state 3
      of respiration, and respiratory control ratio and increased lag phase of
      repolarization. With the exception of state 4 of respiration whose increase
      induced by tamoxifen was reversed by the presence of estradiol, the effects of
      tamoxifen were highly exacerbated when estradiol was present. We observed that 10
      microm tamoxifen in the presence of estradiol affected mitochondria significantly
      by decreasing FCCP-stimulated respiration, state 3 of respiration, respiratory
      control ratio, and ADP depolarization and increasing the lag phase of
      repolarization. All of the deleterious effects induced by 25 microm tamoxifen
      were highly exacerbated in the presence of estradiol. Furthermore, we observed
      that the effects of both compounds were independent of estrogen receptors because
      the pure estrogen antagonist ICI 182,780 did not interfere with tamoxifen and/or
      estradiol detrimental effects. Altogether, our data provide a mechanistic
      explanation for the multiple cytotoxic effects of tamoxifen including its
      capacity to destroy tamoxifen-resistant breast cancer cells in the presence of
      estradiol. This new piece of information provides a basis for the development of
      new and promising anticancer therapeutic strategies.

PMID- 16410253
TI  - Loss of lipoprotein lipase-derived fatty acids leads to increased cardiac glucose
      metabolism and heart dysfunction.
AB  - Long-chain fatty acids (FAs) are the predominant energy substrate utilized by the
      adult heart. The heart can utilize unesterified FA bound to albumin or FA
      obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart
      specific lipoprotein lipase knock-out mice (hLpL0) to test whether these two
      sources of FA are interchangeable and necessary for optimal heart function.
      Hearts unable to obtain FA from lipoprotein TG were able to compensate by
      increasing glucose uptake, glycolysis, and glucose oxidation. HLpL0 hearts had
      decreased expression of pyruvate dehydrogenase kinase 4 and increased
      cardiomyocyte expression of glucose transporter 4. Conversely, FA oxidation rates
      were reduced in isolated perfused hLpL0 hearts. Following abdominal aortic
      constriction expression levels of genes regulating FA and glucose metabolism were
      acutely up-regulated in control and hLpL0 mice, yet all hLpL0 mice died within 48
      h of abdominal aortic constriction. Older hLpL0 mice developed cardiac
      dysfunction characterized by decreased fractional shortening and interstitial and
      perivascular fibrosis. HLpL0 hearts had increased expression of several genes
      associated with transforming growth factor-beta signaling. Thus, long term
      reduction of lipoprotein FA uptake is associated with impaired cardiac function
      despite a compensatory increase in glucose utilization.

PMID- 16410254
TI  - Transcriptional regulation of the osterix (Osx, Sp7) promoter by tumor necrosis
      factor identifies disparate effects of mitogen-activated protein kinase and NF
      kappa B pathways.
AB  - Osteoblast (OB) differentiation is suppressed by tumor necrosis factor-alpha (TNF
      alpha), an inflammatory stimulus that is elevated in arthritis and menopause.
      Because OB differentiation requires the expression of the transcription factor
      osterix (Osx), we investigated TNF effects on Osx. TNF inhibited Osx mRNA in pre
      osteoblastic cells without affecting Osx mRNA half-life. Inhibition was
      independent of new protein synthesis. Analysis of the Osx promoter revealed two
      transcription start sites that direct the expression of an abundant mRNA (Osx1)
      and an alternatively spliced mRNA (Osx2). Promoter fragments driving the
      expression of luciferase were constructed to identify TNF regulatory sequences.
      Two independent promoters were identified upstream of each transcription start
      site. TNF potently inhibited transcription of both promoters. Deletion and
      mutational analysis identified a TNF-responsive region proximal to the Osx2 start
      site that retained responsiveness when inserted upstream of a heterologous
      promoter. The TNF response region was a major binding site for nuclear proteins,
      although TNF did not change binding at the site. The roles of MAPK and NFkappaB
      were investigated as signal mediators of TNF. Inhibitors of MEK1 and ERK1, but
      not of JNK or p38 kinase, abrogated TNF inhibition of Osx mRNA and promoter
      activity. TNF action was not prevented by blockade of NFkappaB nuclear entry. The
      forced expression of high levels of NFkappaB uncovered a proximal promoter
      enhancer; however, this site was not activated by TNF. The inhibitory effect of
      TNF on Osx expression may decrease OB differentiation in arthritis and
      osteoporosis.

PMID- 16410255
TI  - Predicting successful extubation of very low birthweight infants.
AB  - OBJECTIVE: To determine the accuracy of three tests used to predict successful
      extubation of preterm infants. STUDY DESIGN: Mechanically ventilated infants with
      birth weight <1250 g and considered ready for extubation were changed to
      endotracheal continuous positive airway pressure (ET CPAP) for three minutes.
      Tidal volumes, minute ventilation (V e), heart rate, and oxygen saturation were
      recorded before and during ET CPAP. Three tests of extubation success were
      evaluated: (a) expired V e during ET CPAP; (b) ratio of V e during ET CPAP to V e
      during mechanical ventilation (V e ratio); (c) the spontaneous breathing test
      (SBT)-the infant passed this test if there was no hypoxia or bradycardia during
      ET CPAP. The clinical team were blinded to the results, and all infants were
      extubated. Extubation failure was defined as reintubation within 72 hours of
      extubation. RESULTS: Fifty infants were studied and extubated. Eleven (22%) were
      reintubated. The SBT was the most accurate of the three tests, with a sensitivity
      of 97% and specificity of 73% and a positive and negative predictive value for
      extubation success of 93% and 89% respectively. CONCLUSION: The SBT used just
      before extubation of infants <1250 g may reduce the number of extubation
      failures. Further studies are required to establish whether the SBT can be used
      as the primary determinant of an infant's readiness for extubation.

PMID- 16410256
TI  - Accelerated postnatal head growth follows preterm birth.
AB  - BACKGROUND: Poor growth after preterm birth, particularly poor head growth, is
      associated with impaired neurodevelopmental outcome. OBJECTIVE: To evaluate
      weight gain and head growth between birth and term in a contemporary cohort of
      preterm infants, taking into account breast milk intake and illness severity.
      METHODS: Subjects were inborn infants <or=32 weeks gestation who remained in the
      neonatal unit up to >or=37 weeks postmenstrual age. Weight and head circumference
      (HC) were expressed as standard deviation score (SDS), growth between birth and
      discharge as SDS gain (SDSG), and illness severity and breast milk exposure as
      the number of days of level 1 (full) intensive care (%L1IC) and the number of
      days on which breast milk was received (%BM) as a percentage of days from birth
      to discharge. RESULTS: Infants showed poor postnatal weight gain but accelerated
      head growth. There was a highly significant fall in mean (SD) weight SDS between
      birth and discharge (-0.31 (0.96) and -1.32 (1.02) respectively, p<0.001) and a
      highly significant increase in HC SDS (-0.52 (0.95) and -0.03 (1.25)
      respectively, p = 0.003). %L1IC had a highly significant negative impact on
      weight SDSG (p = 0.006), and %BM had a significant positive impact on HC SDSG (p
      = 0.043). CONCLUSIONS: Accelerated postnatal head growth suggests catch up after
      antenatal restraint. This raises the possibility that poor neurocognitive
      outcomes after extremely preterm birth may in part be consequent on poor
      intrauterine brain growth. As postnatal head growth may be facilitated by breast
      milk, there is an urgent need to evaluate the optimal use of breast milk in
      preterm neonates. Illness severity is a significant determinant of poor postnatal
      weight gain.

PMID- 16410257
TI  - Nitric oxide modulates the expression of cell cycle regulatory genes during
      lateral root formation in tomato.
AB  - Nitric oxide (NO) is a bioactive molecule involved in diverse physiological
      functions in plants. It has previously been reported that the NO donor sodium
      nitroprusside (SNP) applied to germinated tomato seeds was able to induce lateral
      root (LR) formation in the same way that auxin treatment does. In this paper, it
      is shown that NO modulates the expression of cell cycle regulatory genes in
      tomato pericycle cells and leads, in turn, to induced LR formation. The addition
      of the NO scavenger CPTIO at different time points during auxin-mediated LR
      development indicates that NO is required for LR primordia formation and not for
      LR emergence. The SNP-mediated LR promotion could be prevented by the cell cycle
      inhibitor olomoucine, suggesting that NO is involved in cell cycle regulation. A
      system was developed in which the formation of LRs was synchronized. It was based
      on the control of NO availability in roots by treatment with the NO scavenger
      CPTIO. The expression of the cell cycle regulatory genes encoding CYCA2;1,
      CYCA3;1, CYCD3;1, CDKA1, and the Kip-Related Protein KRP2 was studied using RT
      PCR analysis in roots with synchronized and non-synchronized LR formation. NO
      mediates the induction of the CYCD3;1 gene and the repression of the CDK
      inhibitor KRP2 gene at the beginning of LR primordia formation. In addition,
      auxin-dependent cell cycle gene regulation was dependent on NO.

PMID- 16410258
TI  - Water uptake by roots of Hordeum marinum: formation of a barrier to radial O2
      loss does not affect root hydraulic conductivity.
AB  - The adventitious roots of Hordeum marinum grown in stagnant deoxygenated solution
      contain a barrier to radial O2 loss (ROL) in basal zones, whereas roots of plants
      grown in aerated solution do not. The present experiments assessed whether
      induction of the barrier to ROL influences root hydraulic conductivity (Lpr).
      Wheat (Triticum aestivum) was also studied since, like H. marinum, this species
      forms aerenchyma in stagnant conditions, but does not form a barrier to ROL.
      Plants were grown in either aerated or stagnant, deoxygenated nutrient solution
      for 21-28 d. Root-sleeving O2 electrodes were used to assess patterns of ROL
      along adventitious roots, and a root-pressure probe and a pressure chamber to
      measure Lpr for individual adventitious roots and whole root systems,
      respectively. Lpr, measured under a hydrostatic pressure gradient, was 1.8-fold
      higher for individual roots, and 5.6-fold higher for whole roots systems, in T.
      aestivum than H. marinum. However, there was no difference in Lpr between the two
      species when measured under an osmotic driving force, when water moved from cell
      to cell rather than apoplastically. Root-zone O2 treatments during growth had no
      effect on Lpr for either species (measured in aerobic solution). It is concluded
      that induction of the barrier to ROL in H. marinum did not significantly affect
      the hydraulic conductivity of either individual adventitious roots or of the
      whole root system.

PMID- 16410259
TI  - Affinity-tags are removed from Cladosporium fulvum effector proteins expressed in
      the tomato leaf apoplast.
AB  - Cladosporium fulvum (syn. Passalora fulva) is a biotrophic fungal pathogen that
      causes leaf mould on tomato (Solanum esculentum). The fungus grows exclusively in
      the tomato leaf apoplast where it secretes several small (<15 kDa) cysteine-rich
      proteins that are thought to play a role in disease establishment. To investigate
      the role of these proteins, and to identify their in planta targets, a targeted
      proteomics approach was undertaken. C. fulvum proteins were expressed as
      recombinant fusion proteins carrying various affinity-tags at either their C- or
      N-terminus. Although these fusion proteins were correctly expressed and secreted
      into the leaf apoplast, detection of affinity-tagged C. fulvum proteins failed,
      and affinity purification did not result in the recovery of these proteins.
      However, when using C. fulvum effector protein-specific antibodies, specific
      signals were obtained for the different proteins. It is concluded that the
      stability of the in planta expressed recombinant fusion proteins is insufficient,
      which results in removal of the affinity-tag from the fusion proteins,
      irrespective of the C- or N-terminal fusion or the nature of the affinity-tag.
      Similar phenomena were observed when the fusion proteins were expressed in other
      Solanaceous species, but not when expressed in Arabidopsis thaliana.

PMID- 16410260
TI  - PpEG4 is a peach endo-beta-1,4-glucanase gene whose expression in climacteric
      peaches does not follow a climacteric pattern.
AB  - In peach (Prunus persica L. Batsch.) the degradation of the pectic compounds of
      the cell wall is considered to be the principal component responsible for fruit
      softening. Many genes encoding enzymes acting on the different polymers of the
      pectic matrix have been shown to be highly expressed during the late phases of
      softening, with polygalacturonase being the most important. Nevertheless, it is
      known that softening starts well before the ethylene climacteric rise which
      occurs concomitant with the maximal expression of the pectolytic enzymes. The
      cloning and characterization of PpEG4, an endo-beta-1,4-glucanase (EGase) gene
      preferentially expressed in preclimacteric fruits, are presented here. PpEG4
      belongs to the group of EGases containing, at their carboxy-terminus, a peptide
      similar to the cellulose binding domain of microbial origin. This EGase is also
      expressed during abscission of both leaves and fruits. The effect of exogenous
      ethylene treatments on PpEG4 transcription is null in young fruits and negative
      in preclimacteric ones, while it is positive in abscission zones. Thus, the
      expression of PpEG4 seems to be more dependent on the type of separation process
      rather than being influenced by a direct hormone action. The ability of the PpEG4
      regulatory sequences to drive transcription in cells undergoing separation events
      is also maintained in tomato, where about 3 kb of the gene promoter could drive
      the expression of gusA in preclimacteric fruits and in the fruit abscission
      zones.

PMID- 16410261
TI  - Analysis of epidemiological cohort data on smoking effects and lung cancer with a
      multi-stage cancer model.
AB  - A stochastic two-stage cancer model is used to analyse the relation between lung
      cancer and cigarette smoking. The model contains the main rate-limiting stages of
      carcinogenesis, which include initiation, promotion (clonal expansion of
      initiated cells), malignant transformation and a lag time for tumour formation.
      Various data sets were used to test the model. These include the data of a large
      prospective collaborative project carried out in 10 different European countries,
      the European Prospective Investigation into Cancer and Nutrition (EPIC). This new
      data set has not been modelled before. The model is also tested on other
      published data from CPS-II (Cancer Prevention Study II) of the American Cancer
      Society and the British doctors' study. The analyses indicate that the EPIC data
      are best described with smoking dependence on the rates of malignant
      transformation and clonal expansion. With increasing smoking rates, saturation
      effects in the two exposure rate-dependent model parameters were observed. The
      results find confirmation in the biological literature, where both mutational
      effects and promotional effects of cigarette smoke are documented.

PMID- 16410262
TI  - The dioxin receptor is silenced by promoter hypermethylation in human acute
      lymphoblastic leukemia through inhibition of Sp1 binding.
AB  - The transcription factor aryl hydrocarbon receptor (AhR) has relevant functions
      in cell proliferation. Interestingly, the AhR can either promote or inhibit
      proliferation depending on the cell phenotype. Although recent data reveal
      potential pathways for AhR signaling in cell proliferation, the mechanisms that
      regulate its activity in tumor cells remain unknown. Here, we have analyzed
      promoter hypermethylation as a potential mechanism controlling AhR expression in
      human tumor cells. AhR promoter CpG methylation was sporadic in a panel of 19
      tumor cell lines except for the chronic myeloid leukemia (CML) K562 and the acute
      lymphoblastic leukemia (ALL) REH. When compared with normal lymphocytes, REH had
      very low constitutive AhR expression that could be attributed to promoter
      hypermethylation since treatment with the DNA demethylating agent 5-aza-2'
      deoxycitidine (AZA) significantly increased AhR mRNA and protein. These results
      in leukemia-derived cell lines were further confirmed in primary ALL, where 33%
      of the patients (7/21) had AhR promoter hypermethylation. Chromatin
      immunoprecipitation (ChIP) showed that methylation impaired binding of the
      transcription factor Sp1 to the AhR promoter, thus providing a mechanism for AhR
      downregulation in REH cells. Therefore, promoter hypermethylation represents a
      novel epigenetic mechanism downregulating AhR activity in hematological
      malignancies such as ALL.

PMID- 16410263
TI  - A V141L polymorphism of the human LRMP gene is associated with survival of lung
      cancer patients.
AB  - Mouse Lrmp and Casc1 genes are candidates for the pulmonary adenoma
      susceptibility 1 (Pas1) locus, the major determinant of strain variation in lung
      tumor susceptibility. These genes contain coding and non-coding single nucleotide
      polymorphisms (SNPs) strongly associated with lung tumor risk in mice. Analysis
      of LRMP and CASC1 gene SNPs in 361 lung adenocarcinoma (ADCA) patients and 327
      healthy controls revealed common SNPs in LRMP (V141L and S197C) and CASC1 (R33S
      and three intronic variations), and none showed a significant association with
      lung ADCA risk. However, in the time-dependent Cox regression model, after
      adjustment for age, gender, smoking history and clinical stage, the carrier
      status of the Leu variation (V141L) of the LRMP gene was associated with higher
      mortality in patients with age at tumor onset < or = 65 years [hazard ratio (HR)
      2.3; 95% CI 1.4-3.7; P = 0.001]. These findings suggest that the LRMP V141L
      polymorphism can predict survival in lung ADCA and that the role of LRMP and
      CASC1 in human lung cancer risk may differ from that in mice.

PMID- 16410264
TI  - Epidemiological MIC cut-off values for tigecycline calculated from Etest MIC
      values using normalized resistance interpretation.
AB  - OBJECTIVES: To apply the normalized resistance interpretation (NRI) method to
      Etest MIC results which have higher precision than conventional log2 dilution MIC
      tests due to the inclusion of intermediate values. If successful, NRI might
      provide an objective tool for the definition of epidemiological MIC cut-off
      values. METHODS: MICs of tigecycline and other antimicrobial agents were
      determined for 4771 clinical isolates comprising five Gram-positive and 13 Gram
      negative species or species groups using the Etest. Histograms of MIC values were
      constructed for each species and NRI calculations were applied to them. An upper
      MIC limit of 2.5 SD above the theoretical mean of the normalized distribution was
      used for setting the epidemiological cut-off values. RESULTS: Calculated cut-off
      values for wild-type strains were between 0.11 and 0.96 mg/L for Gram-positive
      species, and between 0.44 and 8.3 mg/L for Gram-negative species, except for
      Pseudomonas aeruginosa, which had a cut-off value of 450 mg/L, consistent with
      earlier reports on the lack of activity of tigecycline against this species.
      CONCLUSIONS: NRI offers an objective method for the analysis of MICs produced
      using Etests and the determination of epidemiological MIC cut-off values.

PMID- 16410265
TI  - Decreased susceptibility to glycopeptides in methicillin-resistant Staphylococcus
      aureus: a 20 year study in a large French teaching hospital, 1983-2002.
AB  - OBJECTIVES: To assess the evolution of glycopeptide susceptibility in methicillin
      resistant Staphylococcus aureus (MRSA) strains isolated in a large French
      teaching hospital from 1983 to 2002. METHODS: Determination of glycopeptide MICs
      by using the Etest method in Mueller-Hinton agar on a sample of randomly selected
      MRSA strains. RESULTS: A total of 1445 MRSA strains were tested, and one
      vancomycin-intermediate MRSA (VISA) and 31 teicoplanin-intermediate MRSA (TISA)
      strains were detected. The first strains were detected in 1985, and all strains
      were gentamicin resistant (GR). None of the gentamicin-susceptible strains had a
      glycopeptide MIC > 3 mg/L. In addition, there was a significant increase in
      glycopeptide MIC geometric means over the years, and this increase was higher for
      teicoplanin than for vancomycin. CONCLUSIONS: The higher increase in teicoplanin
      MICs, and the good correlation between vancomycin and teicoplanin MICs, suggests
      systematic determination of teicoplanin MIC to screen for abnormal glycopeptide
      susceptibility among GR-MRSA.

PMID- 16410267
TI  - Rhabdomyolysis and acute renal failure in a patient treated with daptomycin.

PMID- 16410266
TI  - Evaluation of the efficacy of albendazole sulphoxide and praziquantel in
      combination on Taenia crassiceps cysts: in vitro studies.
AB  - OBJECTIVES: Praziquantel and albendazole are currently used for chemotherapeutic
      treatment of neurocysticercosis. Albendazole has been found to be more effective
      than praziquantel; however, it is well known that not all patients will show a
      complete resolution of cysts. Searching for more effective treatments, this study
      was designed to evaluate the effect of the combination of praziquantel and
      albendazole sulphoxide in a Taenia crassiceps in vitro model as well as the kind
      of interaction between both drugs. METHODS: In order to determine the
      concentration that produced 50% effect (EC50), T. crassiceps cysts were incubated
      in culture medium containing praziquantel (0.005-0.04 microg/mL), albendazole
      sulphoxide (0.021-0.16 microg/mL) or the combination of praziquantel and
      albendazole sulphoxide in a fixed-dose ratio (1:1). The experimental
      concentration (EC50Exp) of the combination was determined from the concentration
      response curve constructed from the combined drug treatment. Isobolographic
      analyses were used to define the nature of the interaction between praziquantel
      and albendazole sulphoxide. Morphological and ultrastuctural alterations after
      different treatments over the parasite tissue were observed by light and
      transmission electron microscopy. RESULTS: The changes in ultrastructure were
      more marked with the praziquantel and albendazole sulphoxide combination. Also
      the cysticidal effect of the combination was observed earlier than that of each
      drug alone. When isobolographic analysis was employed, we found that the
      experimental EC50 value (0.042 microg/mL) was not significantly different from
      the theoretical EC50 value (0.035 microg/mL), which indicates an additive
      interaction between praziquantel and albendazole sulphoxide. CONCLUSIONS: Our
      study suggests that the combination of praziquantel and albendazole sulphoxide
      could potentially improve the current neurocysticercosis treatment.

PMID- 16410268
TI  - Beneficial effects of orosomucoid on the glomerular barrier in puromycin
      aminonucleoside-induced nephrosis.
AB  - BACKGROUND: In a hitherto unconfirmed report, orosomucoid was reported to
      ameliorate the nephrotic syndrome induced by puromycin aminonucleoside (PAN) in
      rats. METHODS: We wanted to test this hypothesis and extend the analysis of the
      effects on the glomerular barrier. Glomerular filtration rate (GFR), and
      fractional clearance for albumin (theta(albumin)) and for neutral Ficolls were
      estimated in cooled isolated perfused kidneys. Modern transport equations were
      used to estimate glomerular size selectivity and charge selectivity. Also,
      podocyte morphology was studied. Four groups of rats (4 x n = 8) were
      administered PAN intraperitoneally and treated daily for 5 days with orosomucoid
      in two different doses (groups A and B), albumin (group C) or saline (group D).
      Two additional groups of rats (2 x n = 8) were used as controls and these rats
      received either saline (group E) or orosomucoid (group F) but no PAN. RESULTS:
      Treatment with orosomucoid restored podocyte morphology and renal function from
      the damaging effects of PAN in a dose-dependent manner. GFR was significantly
      reduced by PAN (groups C and D) when compared with controls (groups E and F).
      This effect was partly (group A) or completely (group B) reversed by orosomucoid.
      The theta(albumin) was 0.002+/-0.001 (mean+/-SEM) in controls (group E) and was
      unaffected by orosomucoid per se (group F). PAN increased theta(albumin) to
      0.020+/-0.001 in group C and to 0.021+/-0.001 in group D, while it was
      significantly less in group A, 0.014+/-0.001, P<0.05. The heterogeneous charged
      fibre model analysis revealed that PAN reduced the relative volume of negatively
      charged fibres, phi, from 7.1+/-0.08% (group E) to 48% of this value in groups C
      and D (P<0.001); phi was 4.5+/-0.04% in group A, 5.3+/-0.44% in group B, and
      6.1+/-0.11% in group F. CONCLUSION: High doses of orosomucoid completely
      normalized the glomerular barrier in six out of eight animals with puromycin
      induced nephrotic syndrome. Thus, orosomucoid has a promising therapeutic
      potential for certain kidney disorders.

PMID- 16410269
TI  - Macrophages contribute to the initiation of ischaemic acute renal failure in
      rats.
AB  - BACKGROUND: Although neutrophils and T cells are important in mediating renal
      injury following ischaemia/reperfusion, the role of macrophages is still unknown.
      Using liposomal clodronate (LC), we investigated the effect of systemic monocyte
      macrophage depletion on renal damage in ischaemic acute renal failure in rats.
      METHODS: Male Sprague-Dawley rats were injected by LC or liposomal vehicle and
      underwent bilateral renal pedicle clamping (40 min) or sham ischaemia.
      Biochemical and histological renal damage was assessed and gene expression
      kinetics of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL
      1beta), IL-6 and monocyte chemoattractant protein-1 (MCP-1) using quantitative
      real-time reverse transcription-polymerase chain reaction were conducted at 4, 24
      and 72 h after reperfusion. RESULTS: The percentage of peripheral blood monocytes
      and ectodysplasin-1-positive cells in liver decreased significantly in LC-treated
      animals at 24 h. Systemic monocyte-macrophage depletion resulted in (a) less
      severe tubular necrosis, (b) reduced inflammation and (c) reduced apoptosis of
      renal tubular epithelial cells. Gene expression kinetics showed that IL-6 gene
      expression peaked early at 4 h after reperfusion, followed by TNF-alpha, IL-1beta
      and MCP-1 expressions, which peaked at 24 h. Systemic monocyte-macrophage
      depletion significantly reduced these cytokine and chemokine gene expressions.
      CONCLUSIONS: These results suggest that macrophages are an important mediator in
      the initiation period of ischaemia/reperfusion injury and strategies that limit
      initial macrophage infiltration or activation can be useful in the treatment of
      acute renal failure.

PMID- 16410270
TI  - Sudden onset of adult respiratory distress syndrome (ARDS) in a long standing
      chronic haemodialysis patient with lung calcification.

PMID- 16410271
TI  - Clamping of the dialysate outlet line in the Genius dialysis system does not
      alter dialysate flow or clearances.
AB  - BACKGROUND: The Genius dialysis system is advocated as a tool to perform slow
      extended daily dialysis (SLEDD) in patients with acute renal failure at the
      intensive care unit. At low blood flows however, it is sometimes problematic to
      maintain sufficient systemic pressure in the dialysate circuit, a problem that
      can be overcome by clamping the dialysate outflow line. This intervention can
      however decrease the flow in the dialysate circuit, and can thus potentially
      decrease the clearance. This article analyses the impact of this intervention on
      the blood and dialysate flows and on the removal of retention products. METHODS:
      The study was done in 20 stable chronic dialysis patients to avoid additional
      bias caused by changing comorbidities in ICU patients. Patients were treated by
      Genius, once with clamping and once without clamping, cross-over in a randomized
      fashion, and with 1 week interval. Flows in the dialysate and blood circuit were
      measured with a transsonic flow probe. Urea, creatinine, Beta 2 microglobulin and
      phosphate were measured in the dialysate, and in the serum before and after
      dialysis. RESULTS: There was no clinically significant difference in blood or
      dialysate flows, nor in clearance or removal of retention products during the
      sessions with or without clamping. CONCLUSIONS: The technique of using clamping
      of the dialysate outflow line in the Genius system to increase systemic pressure,
      when the system is used in SLEDD, is a safe technique which does not alter the
      clearances.

PMID- 16410272
TI  - Nutritional status partly explains the overestimation of GFR by the Cockcroft and
      Gault formula in diabetic subjects with severe chronic renal failure.

PMID- 16410273
TI  - Association of interferon-gamma +874A polymorphism with reduced long-term
      inflammatory response in haemodialysis patients.
AB  - BACKGROUND: We have studied the effects of interferon (IFN)-gamma allelic
      variations on expression levels of pro- and anti-inflammatory cytokines and on
      long-term inflammatory status in haemodialysis patients. METHODS: Genotyping was
      performed in 123 patients for single nucleotide polymorphisms in the first intron
      of the IFN-gamma gene (+874 T/A). They were prospectively followed for 2 years.
      Cytokine mRNA levels in whole blood cells (detected by real time (RT)-PCR
      technique) and serum C-reactive protein (CRP) concentrations were compared in
      patient groups with different IFN-gamma genotypes. Serum CRP was evaluated every
      month and inflammatory state was defined as percent of abnormal values (above 5
      mg/l) over total determinations. Of the total, 102 patients survived and
      completed 24+/-1 monthly CRP determinations. The IFN-gamma +/-874 A/A, 'low
      producer' genotype was associated with decreased (P<0.05) mRNA levels of IFN
      gamma and of interleukin-6 and with a lower (P<0.05) frequency of CRP elevation
      (37+/-6%) than the +/-874 A/T and T/T, 'intermediate and high-producer' genotypes
      (59+/-6%, and 60+/-5%, respectively). The mRNA levels of tumor necrosis factor
      alpha, IL-10 and of transforming growth factor-beta1 were not different in the
      three groups of patients. Pooled analysis in deceased (10+/-3 monthly CRP
      determinations) and survived patients confirmed the results obtained in the
      patients who completed the follow-up period. CONCLUSIONS: The 'low-producer' IFN
      gamma +874 A/A genotype was associated with a preventive effect on long-term CRP
      elevation in haemodialysis patients possibly mediated by decreased gene
      expression of IFN-gamma and IL-6.

PMID- 16410274
TI  - A hypothesis linking sodium and lithium reabsorption in the distal nephron.
AB  - BACKGROUND: A hypothesis is proposed linking Na(+) and Li(+) reabsorption in the
      distal nephron. The handling of these two ions in the distal nephron is related
      because they share the same apical membrane entry mechanism: the amiloride
      sensitive Na(+) channel (ENaC). However, the two ions exit the cell through
      different transport mechanisms: Na(+) via the Na(+)-K(+)-ATPase and Li(+) via the
      Na(+)/H(+) exchanger. Studies in rats have shown that under normal circumstances
      hardly any Li(+) is reabsorbed in the distal nephron, so that the urinary
      excretion of Li(+), expressed as a fraction of the delivery to the early distal
      tubule (FE(Li dist)), amounts to approximately 0.97. In contrast, during severe
      dietary Na(+) restriction, FE(Li dist) decreases to 0.50-0.60. Our hypothesis is
      that the absence of distal Li(+) reabsorption during intake of a normal diet can
      be explained by a negative driving force for Li(+) entrance across the apical
      membrane in those segments in which ENaC is active. METHOD: We propose a model
      that incorporates this concept. RESULTS: The model indicates that the lowering of
      FE(Li dist) during dietary Na(+) restriction can be explained by activation of
      apical ENaC in extra sub-segments further downstream. In these extra sub-segments
      the driving force for Li(+) reabsorption is positive, leading to significant
      Li(+) reabsorption. During dietary K(+) restriction, FE(Li dist) is reduced to
      0.35-0.55. The model shows that this reduction in FE(Li dist) can be explained by
      hyperpolarization of the apical membrane in ENaC-containing sub-segments, which
      is known to occur in this condition. CONCLUSION: We conclude that the model may
      improve current understanding of both Na(+) and Li(+) handling in the distal
      nephron.

PMID- 16410275
TI  - Pulmonary cavernae in Wegener's granulomatosis.

PMID- 16410276
TI  - Glycaemic control with modified intensive insulin injections (MII) using insulin
      pens and premixed insulin in children with type-1 diabetes: a randomized
      controlled trial.
AB  - The objective of this study was to compare glycemic control and insulin dosage in
      children with type 1 diabetes treated by a modified intensified insulin therapy
      MII using insulin pens (and premixed and regular insulin) with those on
      conventional insulin therapy. This was a longitudinal, randomized controlled
      trial for 6 months or more. From a cohort of 125 children with previously
      diagnosed type-1 diabetes (more than a year after diagnosis) two groups were
      randomly selected Group AI (n=20) and Group B (n=20). Group AI children and 10
      children with recently diagnosed type 1 diabetes (Group AII) were allocated to
      MII using regular insulin and premixed insulin (30/70 and 40/60 and 50/50). Group
      B patients continued their conventional insulin therapy for the whole period of
      the trial. The main outcome measures were glycemic control measured by mean blood
      glucose concentration and percentage of glycated haemoglobin and total daily
      insulin dose. Mean blood glucose concentrations before the three main meals, and
      at midnight, (148, 147, 179 and 127 mg/dl, respectively) were lower in children
      receiving intensified MII compared with those receiving conventional insulin
      therapy (192, 174, 194 and 179 mg/dl, respectively) (standardized mean difference
      34+/-15 mg/dl), equivalent to a difference of 1.9+/-0.8 mmol/l. This improved
      control during MII was achieved with no change in the average daily insulin dose
      in group-AI. In group-AII insulin dose decreased significantly during their first
      6 moths of treatment (honeymooning). Glycemic control is better during MII using
      insulin pens and premixed and regular insulin compared with conventional insulin
      therapy, without any significant change in insulin dose needed to achieve this
      level of control. The difference in glycemic control between the two methods is
      significant and could reduce the risk of micro-vascular complications.

PMID- 16410277
TI  - All together now: from pacemakers to gastric peristalsis.

PMID- 16410278
TI  - Cardiovascular consequences of life-long exposure to dietary isoflavones in the
      rat.
AB  - Dietary soy intake in man is proposed to provide cardiovascular protection, but
      it is not established whether this property is attributable to the soy protein
      per se or to associated dietary isoflavones. This investigation aimed to
      establish whether the dietary isoflavones in soy protein affect cardiovascular
      function. Ten days prior to mating, male and female Wistar rats were habituated
      to either a soy based isoflavone rich diet (plasma concentration 1.87 micromol l(
      1) isoflavones) or the same diet after isoflavone elution (plasma isoflavone not
      detectable). Offspring were weaned onto and maintained on the same diet as their
      dam and sire for 6 months. Blood pressure, and constrictor and dilator responses
      in the aorta and mesenteric resistance arteries were assessed at 3 and 6 months
      of age. There was no effect of isoflavone removal from the diet on blood
      pressure, heart rate, aortic function or mesenteric artery contractile function,
      at either 3 or 6 months of age. Resistance mesenteric arteries from 6-month-old
      female rats fed the isoflavone rich diet demonstrated a modest increase in
      arterial distensibility compared with those fed the depleted diet, and mesenteric
      arteries from male and female rats fed the isoflavone rich diet showed increased
      sensitivity to acetylcholine. In summary, the isoflavone content of soy protein
      has no influence on blood pressure in healthy rats fed a diet based on soy
      protein, but influences small artery function.

PMID- 16410280
TI  - Classification of longissimus lumborum muscle spindle afferents in the
      anaesthetized cat.
AB  - Recordings have been made from 127 single muscle spindle afferents from the
      longissimus lumborum muscles of anaesthetized cats. They have been characterized
      by their responses to passive muscle stretch and the effects of succinylcholine
      (SCh) and by their sensitivity to vibration. The use of SCh permitted the
      assessment for each afferent of the influence of bag1 (b1) and bag2 (b2)
      intrafusal muscle fibres. From this, on the assumption that all afferents were
      affected by chain (c) fibres, they were classified in four groups: b1b2c (41.9%),
      b2c (51.4%), b1c (1.3%) and c (5.4%). All the afferents with b1 influence were
      able to respond one to one to vibration at frequencies above 100 Hz and were
      considered to belong to primary endings. On the basis of the vibration test, 64%
      of the b2c type afferents appeared to be primaries and 36% secondaries. Of the
      units classified as primaries, 41% were designated as b2c and would not therefore
      be able to respond to dynamic fusimotor activity. The significance of this
      relatively high proportion of b2c-type spindle primary afferents is discussed in
      relation to the specialized postural function of the back muscles.

PMID- 16410279
TI  - Dynamic regulation of glycinergic input to spinal dorsal horn neurones by
      muscarinic receptor subtypes in rats.
AB  - Activation of spinal muscarinic acetylcholine receptors (mAChRs) inhibits
      nociception. However, the cellular mechanisms of this action are not fully known.
      In this study, we determined the role of mAChR subtypes in regulation of synaptic
      glycine release in the spinal cord. Whole-cell voltage-clamp recordings were
      performed on lamina II neurones in the rat spinal cord slices. The mAChR agonist
      oxotremorine-M significantly increased the frequency of glycinergic sIPSCs but
      not mIPSCs. Surprisingly, the effect of oxotremorine-M on sIPSCs was largely
      attenuated at a higher concentration. On the other hand, 1-10 microm oxotremorine
      M dose-dependently increased the frequency of sIPSCs in rats pretreated with
      intrathecal pertussis toxin. Furthermore, oxotremorine-M also dose-dependently
      increased the frequency of sIPSCs in the presence of himbacine (an M2/M4 mAChR
      antagonist) or AF-DX116 (an M2 mAChR antagonist). The M3 mAChR antagonist 4-DAMP
      abolished the stimulatory effect of oxotremorine-M on sIPSCs. Interestingly, the
      GABA(B) receptor antagonist CGP55845 potentiated the stimulatory effect of
      oxotremorine-M on sIPSCs. In the presence of CGP55845, both himbacine and AF
      DX116 similarly reduced the potentiating effect of oxotremorine-M on sIPSCs.
      Collectively, these data suggest that the M3 subtype is present on the
      somatodendritic site of glycinergic neurones and is mainly responsible for
      muscarinic potentiation of glycinergic input to spinal dorsal horn neurones.
      Concurrent stimulation of mAChRs on adjacent GABAergic interneurones attenuates
      synaptic glycine release through presynaptic GABA(B) receptors on glycinergic
      interneurones. This study illustrates a complex dynamic interaction between
      GABAergic and glycinergic synapses in the spinal cord dorsal horn.

PMID- 16410281
TI  - Src family kinases play multiple roles in differentiation of trophoblasts from
      human term placenta.
AB  - Tyrosine phosphorylation plays a major role in controlling many biological
      processes in different cell types. Src family kinases (SFKs) are one of the most
      studied groups of tyrosine kinases and can mediate a variety of signalling
      pathways. However, little is known about the expression of SFKs in human term
      placenta and their implication in trophoblast differentiation. Therefore, we
      examined the expression profile of SFK members over time in culture and their
      implication in differentiation. In vitro, freshly isolated cytotrophoblast cells,
      cultured in 10% fetal bovine serum (FBS), spontaneously aggregate and fuse to
      form multinucleated cells that resemble phenotypically mature
      syncytiotrophoblasts, that concomitantly produce human chorionic gonadotropin
      (hCG) and human placental lactogen (hPL). In this study, we showed that
      trophoblasts expressed all SFK members and some of them are expressed as
      different splice variants. Moreover, using real-time PCR, this study showed two
      different expression profiles of SFKs in human trophoblasts during culture. In
      addition, the protein level and phosphorylation status of Src were evaluated
      using specific antibodies. Src was rapidly phosphorylated at Tyr-416 and
      dephosphorylated at Tyr-527 after FBS addition. Surprisingly, inhibition of SFKs
      by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2) or
      herbimycin A had different effects on trophoblast differentiation. While
      herbimycin A inhibited morphological and hormonal differentiation, PP2 stimulated
      hormonal differentiation and inhibited cell adhesion and spreading with no effect
      on cell fusion. In summary, this study showed that SFKs play different roles in
      trophoblast differentiation, probably depending on SFK members activated. Thus,
      this study increases our knowledge and understanding of pathology related to
      impaired trophoblast differentiation such as pre-eclampsia and trophoblast
      neoplasm.

PMID- 16410284
TI  - Intracellular activity of cortical and thalamic neurones during high-voltage
      rhythmic spike discharge in Long-Evans rats in vivo.
AB  - Spontaneous high-voltage rhythmic spike (HVRS) discharges at 6-12 Hz have been
      widely described in the electrocorticogram (EcoG) of Long-Evans rats. These ECoG
      oscillations have been proposed to reflect a state of attentive immobility
      allowing the optimization of sensory integration within the corticothalamic
      pathway. This hypothesis has been challenged by recent studies emphasizing
      similarities between HVRS discharges and spike-and-wave discharges (SWDs) in well
      established rat genetic models of absence epilepsy. Here, we made in vivo
      intracellular recordings to determine, for the first time, the cellular
      mechanisms responsible for the synchronized oscillations in the corticothalamic
      loop during HVRS discharges in the Long-Evans rats. We show that HVRS discharges
      are associated in corticothalamic neurones with rhythmic suprathreshold synaptic
      depolarizations superimposed on a tonic hyperpolarization, likely due to a
      process of synaptic disfacilitation. Simultaneously, thalamocortical neurones
      exhibit a large-amplitude 'croissant'-shaped membrane hyperpolarization with a
      voltage sensitivity suggesting a potassium-dependent mechanism. This thalamic
      hyperpolarizing envelope was associated with a membrane oscillation resulting
      from interactions between excitatory synaptic inputs, a chloride-dependent
      inhibitory conductance and voltage-gated intrinsic currents. These cortical and
      thalamic cellular mechanisms underlying HVRS activity in Long-Evans rats are
      remarkably similar to those previously described in the thalamocortical networks
      during SWDs. Thus, the present study provides an additional support to the
      hypothesis that HVRS activity in Long-Evans rats is an absence-like seizure
      activity.

PMID- 16410286
TI  - Risk stratification in acute coronary syndromes--does the TIMI risk score work in
      unselected cases?
AB  - BACKGROUND: Management of patients with an acute coronary syndrome (ACS) requires
      accurate risk stratification to guide appropriate therapy. AIM: To assess the
      utility of the TIMI risk score in stratifying patients with possible ACS in
      routine clinical practice. DESIGN: Prospective observational study. METHODS: We
      recruited 869 consecutive patients with a diagnosis of possible ACS attending the
      acute medical receiving unit of a district general hospital. The main outcome
      measures were recurrent myocardial infarction, urgent revascularization, and all
      cause mortality. TIMI risk score was calculated for each patient, and each was
      also assigned a risk group based on electrocardiogram (ECG) changes and troponin
      levels only. After follow-up, Cox univariate and multivariate regression was used
      to evaluate the influence of potential risk factors on duration of event-free
      survival, and likelihood ratio tests to assess the fit of the models. RESULTS:
      Increasing TIMI risk score was associated with increased risk of events
      (p<0.001), as was higher risk group from ECG plus troponin stratification
      (p<0.001). The likelihood ratio comparison favoured the TIMI risk score
      (difference 13.910, 5 degrees of freedom, p = 0.016). DISCUSSION: The TIMI risk
      score is a valid tool for risk stratification in unselected cases with possible
      acute coronary syndrome. It is superior to ECG changes and troponin alone,
      although this simpler method also achieves good risk stratification.

PMID- 16410283
TI  - Cardiac system bioenergetics: metabolic basis of the Frank-Starling law.
AB  - The fundamental principle of cardiac behaviour is described by the Frank-Starling
      law relating force of contraction during systole with end-diastolic volume. While
      both work and respiration rates increase linearly with imposed load, the basis of
      mechano-energetic coupling in heart muscle has remained a long-standing enigma.
      Here, we highlight advances made in understanding of complex cellular and
      molecular mechanisms that orchestrate coupling of mitochondrial oxidative
      phosphorylation with ATP utilization for muscle contraction. Cardiac system
      bioenergetics critically depends on an interrelated metabolic infrastructure
      regulating mitochondrial respiration and energy fluxes throughout cellular
      compartments. The data reviewed indicate the significance of two interrelated
      systems regulating mitochondrial respiration and energy fluxes in cells: (1) the
      creatine kinase, adenylate kinase and glycolytic pathways that communicate flux
      changes generated by cellular ATPases within structurally organized enzymatic
      modules and networks; and (2) a secondary system based on mitochondrial
      participation in cellular calcium cycle, which adjusts substrate oxidation and
      energy-transducing processes to meet increasing cellular energy demands. By
      conveying energetic signals to metabolic sensors, coupled phosphotransfer
      reactions provide a high-fidelity regulation of the excitation-contraction cycle.
      Such integration of energetics with calcium signalling systems provides the basis
      for 'metabolic pacing', synchronizing the cellular electrical and mechanical
      activities with energy supply processes.

PMID- 16410287
TI  - Fluroscopy in paediatric fractures--setting a local diagnostic reference level.
AB  - BACKGROUND: The ionizing radiations (Medical Exposure) Regulation 2000 has made
      it mandatory to establish diagnostic reference levels (DRLs) for all typical
      radiological examinations. OBJECTIVES: We attempt to provide dose data for some
      common fluoroscopic procedures used in orthopaedic trauma that may be used as the
      basis for setting DRLs for paediatric patients. MATERIALS AND METHODS: The dose
      area product (DAP) in 865 paediatric trauma examinations was analysed. Median DAP
      values and screening times for each procedure type along with quartile values for
      each range are presented. RESULTS: In the upper limb, elbow examinations had
      maximum exposure with a median DAP value of 1.21 cGy cm2. Median DAP values for
      forearm and wrist examinations were 0.708 and 0.538 cGy cm2, respectively. In
      lower limb, tibia and fibula examinations had a median DAP value of 3.23 cGy cm2
      followed by ankle examinations with a median DAP of 3.10 cGy cm2. The rounded
      third quartile DAP value for each distribution can be used as a provisional DRL
      for the specific procedure type.

PMID- 16410288
TI  - Estimation of photon dose generated by a short pulse high power laser.
AB  - The authors obtain a new equation to estimate the forward component of a photon
      dose generated through the interaction between a target and a short pulse high
      power laser. As the equation is quite simple, it is useful for calculating the
      photon dose. The equation shows that the photon dose is proportional to the
      electron temperature in the range>3 MeV and proportional to the square of the
      electron temperature in the range<3 MeV. The dose estimated with this method is
      roughly consistent with the result of Monte Carlo simulation. With some
      assumptions and corrections, it can reproduce experimental results obtained and
      the dose result calculated at other laboratories.

PMID- 16410285
TI  - Dopamine-dependent non-linear correlation between subthalamic rhythms in
      Parkinson's disease.
AB  - The basic information architecture in the basal ganglia circuit is under debate.
      Whereas anatomical studies quantify extensive convergence/divergence patterns in
      the circuit, suggesting an information sharing scheme, neurophysiological studies
      report an absence of linear correlation between single neurones in normal
      animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients
      single neurones become linearly correlated, thus leading to a loss of segregation
      between neurones. Here we propose a possible integrative solution to this debate,
      by extending the concept of functional segregation from the cellular level to the
      network level. To this end, we recorded local field potentials (LFPs) from
      electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus
      (STN) of parkinsonian patients. By applying bispectral analysis, we found that in
      the absence of dopamine stimulation STN LFP rhythms became non-linearly
      correlated, thus leading to a loss of segregation between rhythms. Non-linear
      correlation was particularly consistent between the low-beta rhythm (13-20 Hz)
      and the high-beta rhythm (20-35 Hz). Levodopa administration significantly
      decreased these non-linear correlations, therefore increasing segregation between
      rhythms. These results suggest that the extensive convergence/divergence in the
      basal ganglia circuit is physiologically necessary to sustain LFP rhythms
      distributed in large ensembles of neurones, but is not sufficient to induce
      correlated firing between neurone pairs. Conversely, loss of dopamine generates
      pathological linear correlation between neurone pairs, alters the patterns within
      LFP rhythms, and induces non-linear correlation between LFP rhythms operating at
      different frequencies. The pathophysiology of information processing in the human
      basal ganglia therefore involves not only activities of individual rhythms, but
      also interactions between rhythms.

PMID- 16410289
TI  - Quality assurance of environmental gamma radiation monitoring in Slovenia.
AB  - Environmental gamma radiation monitoring established in Slovenia consists of a
      network of multifunctional gamma monitors (MFMs) based on pairs of Geiger-Muller
      counters and a network of measuring sites with high-sensitive thermoluminiscence
      dosemeters. The measuring points are evenly spread across Slovenia, located at
      the meteorological stations and more densely on additional locations around the
      Krsko NPP. The MFM network has a 2-fold function with one sensor used for the
      purpose of early warning system in near surroundings of the NPP and the other,
      more sensitive, for natural radiation monitoring. The paper summarises activities
      to establish quality assurance of the environmental gamma radiation measurements
      in Slovenia, with a critical view of the results in comparison with the
      international standards and recommendations. While the results of linearity and
      energy dependence tests were satisfying, on-field intercomparison showed that the
      inherent signal of one of the monitors (MFM) has to be taken into account in the
      range of environmental background radiation.

PMID- 16410290
TI  - Simultaneous measurements of indoor radon, radon-thoron progeny and high
      resolution gamma spectrometry in Greek dwellings.
AB  - Simultaneous indoor radon, radon-thoron progeny and high-resolution in situ gamma
      spectrometry measurements, with portable high-purity Ge detector were performed
      in 26 dwellings of Thessaloniki, the second largest town of Greece, during March
      2003-January 2005. The radon gas was measured with an AlphaGUARD ionisation
      chamber (in each of the 26 dwellings) every 10 min, for a time period between 7
      and 10 d. Most of the values of radon gas concentration are between 20 and 30 Bq
      m(-3), with an arithmetic mean of 34 Bq m(-3). The maximum measured value of
      radon gas concentration is 516 Bq m(-3). The comparison between the radon gas
      measurements, performed with AlphaGUARD and short-term electret ionisation
      chamber, shows very good agreement, taking into account the relative short time
      period of the measurement and the relative low radon gas concentration. Radon and
      thoron progeny were measured with a SILENA (model 4s) instrument. From the radon
      and radon progeny measurements, the equilibrium factor F could be deduced. Most
      of the measurements of the equilibrium factor are within the range 0.4-0.5. The
      mean value of the equilibrium factor F is 0.49 +/- 0.10, i.e. close to the
      typical value of 0.4 adopted by UNSCEAR. The mean equilibrium equivalent thoron
      concentration measured in the 26 dwellings is EEC(thoron) = 1.38 +/- 0.79 Bq m(
      3). The mean equilibrium equivalent thoron to radon ratio concentration, measured
      in the 26 dwellings, is 0.1 +/- 0.06. The mean total absorbed dose rate in air,
      owing to gamma radiation, is 58 +/- 12 nGy h(-1). The contribution of the
      different radionuclides to the total indoor gamma dose rate in air is 38% due to
      40K, 36% due to thorium series and 26% due to uranium series. The annual
      effective dose, due to the different source terms (radon, thoron and external
      gamma radiation), is 1.05, 0.39 and 0.28 mSv, respectively.

PMID- 16410291
TI  - Uncertainty of the thyroid dose conversion factor for inhalation intakes of 131I
      and its parametric uncertainty.
AB  - Inhalation exposures of 131I may occur in the physical form of a gas as well as a
      particulate. The physical characteristics pertaining to these different types of
      releases influence the intake and subsequent dose to an exposed individual. The
      thyroid dose received is influenced by the route through which 131I enters the
      body and its subsequent clearance, absorption and movement throughout the body.
      The radioactive iodine taken up in the gas-exchange tissues is cleared to other
      tissues or absorbed into the bloodstream of the individual and transferred to
      other organs. Iodine in the circulatory system is then taken up by the thyroid
      gland with resulting dose to that tissue. The magnitude of and uncertainty in the
      thyroid dose is important to the assessment of individuals exposed to airborne
      releases of radioiodine. Age- and gender-specific modelling parameters have
      resulted in significant differences between gas uptake, particulate deposition
      and inhalation dose conversion factors for each age and gender group. Inhalation
      dose conversion factors and their inherent uncertainty are markedly affected by
      the type of iodine intake. These differences are expected due to the modelling of
      particulate deposition versus uptake of gas in the respiratory tract. Inhalation
      dose estimates via iodine gases are very similar and separate classifications may
      not be necessarily based on this assessment.

PMID- 16410292
TI  - ELF field in the proximity of complex power line configuration measurement
      procedures.
AB  - The issue of how to measure magnetic induction fields generated by various power
      line configurations, when there are several power lines that run across the same
      exposure area, has become a matter of interest and study within the Regional
      Environment Protection Agency of Friuli Venezia Giulia. In classifying the
      various power line typologies the definition of double circuit line was given: in
      this instance the magnetic field is determined by knowing the electrical and
      geometric parameters of the line. In the case of independent lines instead, the
      field is undetermined. It is therefore pointed out how, in the latter case,
      extracting previsional information from a set of measurements of the magnetic
      field alone is impossible. Making measurements throughout the territory of
      service has in several cases offered the opportunity to define standard
      operational procedures.

PMID- 16410293
TI  - Natural radionuclides in the rocks of the Valle del Cervo Pluton in Piedmont.
AB  - Monitoring of the gamma radiation in Valle del Cervo Pluton was performed by
      determining U and Th contents in the main rock types cropping out over the entire
      area and pertaining to the granitic complex, syenitic complex and monzonitic
      complex. In particular, syenitic rocks were largely used as building and
      ornamental materials (e.g. Sienite della Balma). All the samples are fresh and do
      not present joints or fractures filled with U minerals. In the crushed samples
      the activity of uranium varies from 346 to 764 Bq/kg. Concentration of thorium
      varies from 202 to 478 Bq/kg. For all the analysed rocks uranium activity is
      higher than thorium one. The lowest value of radioactive concentration is
      referred to rocks of the granitic complex. The most active rocks are syenites.
      The data confirm the high activities of Valle del Cervo rock types, strongly
      connected with high K content of the source magma (geochemical signature); on the
      contrary, the activity seems to be not related to the location of the samples.

PMID- 16410294
TI  - Obtaining an unbiased estimate of intake in routine monitoring when the time of
      intake is unknown.
AB  - A common problem in internal dosimetry occurs in routine monitoring, when it is
      required to estimate an intake from a measurement made at the end of a monitoring
      interval, and the time of intake is unknown. ICRP suggests that, in these cases,
      it should be assumed that the intake occurred in the middle of the monitoring
      period. However, it has been shown that this will, in the long term, lead to
      biased estimates of a worker's intake and dose. In order to overcome this
      biasing, the United States Department of Energy (USDOE) recommends a different
      method based on calculating the intakes for all possible intake-times in the
      interval, and then taking an arithmetic average. In this paper, it is shown that
      both the ICRP and USDOE methods are biased. An alternative method is suggested,
      which assumes a constant chronic intake throughout the monitoring interval. Monte
      Carlo simulations are used to estimate the magnitude of bias for two realistic
      monitoring programmes using all three methods. It is shown that the proposed
      method is unbiased and also yields estimates of intake that are generally closer
      to the actual intake, than the other two. The Monte Carlo conclusions are backed
      up by a theoretical analysis of bias. Finally, the source of bias in the
      apparently intuitive approach of the USDOE method is revealed by viewing the
      problem from a Bayesian perspective.

PMID- 16410295
TI  - Physical phantom of typical Korean male for radiation protection purpose.
AB  - Dose distribution within a human body can be measured using physical
      anthropomorphic phantoms. In an effort to establish reference Korean physical
      model, the first Korean physical phantom of average Korean adult male was
      constructed using computed tomography (CT) images of a healthy volunteer. The
      body dimension of the subject was close to that of average Korean male. The
      source images were obtained using fusion positron emission tomography machine at
      Radiation Health Research Institute in Korea, and ported into rapid prototyping
      process. The physical phantom was composed of three tissue-equivalent materials:
      epoxy resin, urethane foam and polyurethane representing bone, lungs and soft
      tissues, respectively. The densities of the tissue-equivalent materials were
      close to those recommended by the International Commission on Radiation Units and
      measurements. To facilitate dose mapping, the phantom was sliced into 2 cm
      sections. Hole grids for thermoluminescence (TL) dosemeter chips were drilled. To
      verify the appropriateness of the physical phantom, organ doses of selected
      organs were measured for reference photon beam, and compared with those computed
      by tomographic model constructed from the same CT images. Absorbed doses
      converted from TL relative response showed good agreement within 7% with those
      calculated.

PMID- 16410296
TI  - Stress history and pubertal development interact to shape hypothalamic-pituitary
      adrenal axis plasticity.
AB  - Both the magnitude and the duration of the hormonal stress response change
      dramatically during neonatal development and aging as well as with prior
      experience with a stressor. However, surprisingly little is known with regard to
      how pubertal maturation and experience with stress interact to affect
      hypothalamic-pituitary-adrenal axis responsiveness. Because adolescence is a
      period of neurodevelopmental vulnerabilities and opportunities that may be
      especially sensitive to stress, it is imperative to more fully understand these
      interactions. Thus, we examined hormonal and neural responses in prepubertal (28
      d of age) and adult (77 d of age) male rats after exposure to acute (30 min) or
      more chronic (30 min/d for 7 d) restraint stress. We report here that after acute
      stress, prepubertal males exhibited a significantly prolonged hormonal stress
      response (e.g. ACTH and total and free corticosterone) compared with adults. In
      contrast, after chronic stress, prepubertal males exhibited a higher response
      immediately after the stressor, but a faster return to baseline, compared with
      adults. Additionally, we demonstrate that this differential stress reactivity is
      associated with differential neuronal activation in the paraventricular nucleus
      of the hypothalamus, as measured by FOS immunohistochemistry. Using triple-label
      immunofluorescence histochemistry, we found that a larger proportion of CRH, but
      not arginine vasopressin, cells are activated in the arginine vasopressin in
      response to both acute and chronic stress in prepubertal animals compared with
      adults. These data indicate that experience-dependent plasticity of the
      hypothalamic-pituitary-adrenal neuroendocrine axis is significantly influenced by
      pubertal maturation.

PMID- 16410297
TI  - Melanocortin modulation of inflammatory cytokine and neuroendocrine responses to
      endotoxin in the monkey.
AB  - alpha-MSH has potent antiinflammatory properties, but little is known about the
      specific melanocortin receptors (MC-Rs) that mediate these effects or about the
      role of the melanocortin system in modulating cytokine responses to an
      inflammatory challenge in the primate in vivo. We, therefore, studied the effects
      of infusion of the alpha-MSH agonist, [Nle(4),d-Phe(7)]-alpha-MSH (NDP-MSH); the
      alpha-MSH antagonist, SHU9119; and the selective MC3-R agonist, D-Trp8-gamma-MSH,
      compared with saline, on proinflammatory cytokine (TNF-alpha, IL-1beta, and IL
      6), antiinflammatory cytokine [IL-10 and IL-1 receptor antagonist (IL-1ra)], and
      pituitary-adrenal responses to endotoxin in ovariectomized monkeys. In the first
      study NDP-MSH or SHU9119 was infused iv for 7 h starting at 0800 h, endotoxin was
      injected at 1000 h, and serial blood samples were collected (n = 6). NDP-MSH
      significantly attenuated proinflammatory cytokine responses to endotoxin. The
      area under the response curve (AUC) decreased by 61% for TNF-alpha (P = 0.02),
      47% for IL-1beta (P = 0.02), and 41% for IL-6 (P = 0.04); there was no effect on
      IL-1ra or IL-10. SHU9119 did not affect proinflammatory cytokine responses, but
      decreased the IL-10 response by 31% (P = 0.03). NDP-MSH also attenuated ACTH (P <
      0.001) and cortisol (P = 0.02) responses. In a second study, the effects of d
      Trp8-gamma-MSH were similarly examined in seven monkeys. The AUC for IL-6 was
      decreased by 37% (P = 0.04) by d-Trp8-gamma-MSH; the AUC for IL-10 was increased
      by 22%, but this was not significant. However, the ratio of IL-6 to IL-10 was
      significantly decreased by d-Trp8-gamma-MSH (P = 0.04), consistent with a
      relatively more antiinflammatory cytokine environment. These results indicate
      that NDP-MSH can attenuate proinflammatory cytokine responses in the primate,
      consistent with previous studies in the rodent, and provide new evidence for a
      role for MC3-R in this process. Moreover, they show for the first time that
      SHU9119, a mixed MC3/4-R antagonist, can decrease the IL-10 response,
      establishing a physiological role for endogenous MSH in modulating the release of
      an antiinflammatory cytokine.

PMID- 16410298
TI  - Hemodynamic, hormonal, and renal actions of adrenomedullin-2 in normal conscious
      sheep.
AB  - Although blood pressure and heart rate effects have been reported for
      adrenomedullin 2 (AM-2), a new member of the calcitonin gene-related peptide
      superfamily, little information is available regarding other biological actions
      of systemically administered AM-2. Accordingly, we report for the first time the
      integrated hemodynamic, hormonal, and renal actions of the AM-2 in normal
      conscious sheep. AM-2 induced significant reductions in mean arterial pressure (P
      < 0.001). This was associated with dose-dependent rises in heart rate (P < 0.001)
      and cardiac output (P < 0.001) and dose-dependent falls in calculated total
      peripheral resistance (P < 0.001). Right atrial pressure was increased post
      infusion (P = 0.026), whereas hematocrit fell post infusion (P = 0.001). AM-2
      also induced significant hormonal changes, particularly in the renin-angiotensin
      aldosterone system where plasma renin activity was significantly activated (P <
      0.001) associated with a dose-dependent rise in plasma aldosterone (P < 0.001).
      Plasma cAMP also rose in response to AM-2 (P < 0.001), as did circulating levels
      of the natriuretic peptides, particularly post infusion. In conclusion, iv
      infusions of AM-2 administered to normal conscious sheep induced significant
      hemodynamic actions including reduced mean arterial pressure and calculated total
      peripheral resistance and increased heart rate and cardiac output. Concurrently,
      AM-2 activated plasma cAMP, plasma renin activity, aldosterone, and the
      natriuretic peptides. With the exception of actions on aldosterone, these actions
      are similar to those previously reported for AM. Thus, AM-2 may be another
      important regulator of volume and pressure homeostasis and may play a role in the
      pathophysiology of heart disease.

PMID- 16410299
TI  - Dihydrotestosterone differentially modulates the mitogen-activated protein kinase
      and the phosphoinositide 3-kinase/Akt pathways through the nuclear and novel
      membrane androgen receptor in C6 cells.
AB  - Androgens such as dihydrotestosterone (DHT) are known to exert their effects
      through the activation of intracellular receptors that regulate the transcription
      of target genes. Alternatively, nongenomic mechanisms, including the activation
      of such signaling pathways as the MAPK pathways, have been described. It is
      unclear, however, whether this latter mechanism of action is mediated by the
      classical androgen receptor (AR) or some alternative mechanism. In this study,
      using a glial cell model (C6 cells) that we found to express the AR, we
      identified that DHT increased the phosphorylation of both ERK and Akt, key
      effectors of the neuroprotection-associated MAPK and phosphoinositide 3-kinase
      signaling pathways, respectively, and ERK phosphorylation was blocked by the AR
      antagonist, flutamide. In contrast, the membrane-impermeable, BSA-conjugated
      androgen (DHT-BSA) caused a dose-dependent suppression of ERK and Akt
      phosphorylation, suggesting the existence of a novel membrane-associated AR that
      mediates this opposite effect on neuroprotective signaling. This is also
      supported by the observation of DHT-displaceable binding sites on the cell
      surface of live C6 cells. Collectively, these data support the existence of a
      novel membrane-associated AR in glial cells and argue for the existence of two,
      potentially competing, pathways in a given cell or tissue. This mutual antagonism
      was supported by the ability of DHT-BSA to attenuate DHT-induced ERK
      phosphorylation. Thus, depending on the predominance of one receptor mechanism
      over another, the outcome of androgen treatment may be very different and, as
      such, could help explain existing discrepancies as to whether androgens are
      protective or damage inducing.

PMID- 16410300
TI  - Immunoglobulin G from patients with Graves' disease induces interleukin-16 and
      RANTES expression in cultured human thyrocytes: a putative mechanism for T-cell
      infiltration of the thyroid in autoimmune disease.
AB  - Mechanisms underlying lymphocyte infiltration of the thyroid gland and orbit in
      Graves' disease (GD) are poorly understood. The IGF-I receptor (IGF-IR) is a
      newly recognized self-antigen that, when activated in GD fibroblasts by IGF-I or
      GD-IgGs, provokes the expression of IL-16 and RANTES (regulated upon activation,
      normal T cell expressed and secreted)-dependent T lymphocyte chemoattraction and
      hyaluronan synthesis. IL-16 is a CD4(+)-specific ligand, and RANTES is a C-C
      chemokine. Here we report that IGF-I and GD-IgG could induce IL-16 and RANTES in
      cultured human thyrocytes in a time-dependent manner. Importantly, human TSH
      failed to induce either chemoattractant. This induction could be attenuated by
      dexamethasone. Rapamycin, a specific inhibitor of the FRAP/mammalian target of
      rapamycin/p70(s6k) pathway, prevented GD-IgG-provoked IL-16 synthesis. IH7, a
      monoclonal antibody directed at IGF-IR also blocked the induction of
      chemoattraction as well as RANTES mRNA synthesis. Our findings suggest that
      thyrocytes can be activated by GD-IgG and IGF-I to express powerful T-cell
      chemoattractants. These actions of GD-IgG appear to be mediated through pathways
      independent of the TSH receptor. Thus, in GD, thyrocytes may participate directly
      in lymphocyte recruitment through their expression of IL-16 and RANTES.

PMID- 16410301
TI  - Dynamic changes in mitogen-activated protein kinase (MAPK) activities in the
      corpus luteum of the bonnet monkey (Macaca radiata) during development, induced
      luteolysis, and simulated early pregnancy: a role for p38 MAPK in the regulation
      of luteal function.
AB  - Changes in MAPK activities were examined in the corpus luteum (CL) during
      luteolysis and pregnancy, employing GnRH antagonist (Cetrorelix)-induced
      luteolysis, stages of CL, and hCG treatment to mimic early pregnancy as model
      systems in the bonnet monkey. We hypothesized that MAPKs could serve to
      phosphorylate critical phosphoproteins to regulate luteal function. Analysis of
      several indices for structural (caspase-3 activity and DNA fragmentation) and
      functional (progesterone and steroidogenic acute regulatory protein expression)
      changes in the CL revealed that the decreased luteal function observed during
      Cetrorelix treatment and late luteal phase was associated with increased caspase
      3 activity and DNA fragmentation. As expected, human chorionic gonadotropin
      treatment dramatically increased luteal function, but the indices for structural
      changes were only partially attenuated. All three MAPKs appeared to be
      constitutively active in the mid-luteal-phase CL, and activities of ERK-1/2 and
      p38-MAPK (p38), but not Jun N-terminal kinase (JNK)-1/2, decreased significantly
      (P < 0.05) within 12-24 h after Cetrorelix treatment. During the late luteal
      phase, in contrast to decreased ERK-1/2 and p38 activities, JNK-1/2 activities
      increased significantly (P < 0.05). Although human chorionic gonadotropin
      treatment increased ERK-1/2 and p38 activities, it decreased JNK-1/2 activities.
      The activation status of p38 was correlated with the phosphorylation status of an
      upstream activator, MAPK kinase-3/6 and the expression of MAPK activated protein
      kinase-3, a downstream target. Intraluteal administration of p38 kinase inhibitor
      (SB203580), but not MAPK kinase-1/2 inhibitor (PD98059), decreased the luteal
      function. Together, these data suggest an important role for p38 in the
      regulation of CL function in primates.

PMID- 16410302
TI  - Effects of hepatic expression of the high-density lipoprotein receptor SR-BI on
      lipoprotein metabolism and female fertility.
AB  - The etiology of human female infertility is often uncertain. The sterility of
      high-density lipoprotein (HDL) receptor-negative (SR-BI(-/-)) female mice
      suggests a link between female infertility and abnormal lipoprotein metabolism.
      SR-BI(-/-) mice exhibit elevated plasma total cholesterol [with normal-sized and
      abnormally large HDL and high unesterified to total plasma cholesterol (UC:TC)
      ratio]. We explored the influence of hepatic SR-BI on female fertility by
      inducing hepatic SR-BI expression in SR-BI(-/-) animals by adenovirus
      transduction or stable transgenesis. For transgenes, we used both wild-type SR-BI
      and a double-point mutant, Q402R/Q418R (SR-BI-RR), which is unable to bind to and
      mediate lipid transfer from wild-type HDL normally, but retains virtually normal
      lipid transport activities with low-density lipoprotein. Essentially wild-type
      levels of hepatic SR-BI expression in SR-BI(-/-) mice restored to nearly normal
      the HDL size distribution and plasma UC:TC ratio, whereas approximately 7- to 40
      fold overexpression dramatically lowered plasma TC and increased biliary
      cholesterol secretion. In contrast, SR-BI-RR overexpression had little effect on
      SR-BI(+/+) mice, but in SR-BI(-/-) mice, it substantially reduced levels of
      abnormally large HDL and normalized the UC:TC ratio. In all cases, hepatic
      transgenic expression restored female fertility. Overexpression in SR-BI(-/-)
      mice of lecithin:cholesterol acyl transferase, which esterifies plasma HDL
      cholesterol, did not normalize the UC:TC ratio, probably because the abnormal HDL
      was a poor substrate, and did not restore fertility. Thus, hepatic SR-BI-mediated
      lipoprotein metabolism influences murine female fertility, raising the
      possibility that dyslipidemia might contribute to human female infertility and
      that targeting lipoprotein metabolism might complement current assisted
      reproductive technologies.

PMID- 16410303
TI  - Haplotype insufficiency for suppressor of cytokine signaling-2 enhances
      intestinal growth and promotes polyp formation in growth hormone-transgenic mice.
AB  - GH may improve intestinal growth or function in patients with short bowel
      syndrome. Excessive trophic effects of GH or IGF-I may contribute to neoplastic
      growth or increased colorectal cancer risk in acromegaly. Identification of
      mechanisms that limit the tumorigenic potential of GH and IGF-I is desirable.
      Suppressor of cytokine signaling-2 (SOCS2) limits GH action on body and organ
      growth, but its role in GH action on intestine is unknown. We tested the
      hypothesis that SOCS2 limits GH-induced intestinal growth or neoplasia in vivo.
      GH-transgenic (GH-TG) mice were crossed with SOCS2 null mice to generate wild
      type (WT) or transgenic (TG) mice with zero (HO-WT; HO-TG), one (HT-WT; HT-TG),
      or two (WT-WT; WT-TG) functional SOCS2 genes. No HO-TG mice were derived from
      crossbreeding. WT-WT, HT-WT, WT-TG, and HT-TG were compared. Body weight, small
      intestine and colon growth, and levels of jejunal IGF-I and sucrase-isomaltase
      mRNAs were assessed. Colon was analyzed for abnormal lesions. HT-WT did not
      differ from WT-WT. Compared with WT-TG, HT-TG had significantly increased body
      weight, small intestine growth, and local IGF-I expression and decreased sucrase
      isomaltase expression. HT-TG colon spontaneously developed multiple hyperplastic
      and lymphoid polyps. GH-induced activation of STAT5 DNA binding activity was
      enhanced in intestine of SOCS2 null mice compared with WT control. Haplotype
      insufficiency for SOCS2 promotes trophic actions of GH in small intestine and
      promotes preneoplastic growth in colon during excess GH. Small variations in
      SOCS2 expression levels may significantly influence the outcome of therapeutic GH
      or acromegaly in intestine.

PMID- 16410304
TI  - Endothelin-2 in ovarian follicle rupture.
AB  - The ovulatory process is activated by a surge of LH, a pituitary gonadotropin,
      which initiates a cohort of dramatic changes in biochemical, physical, and gene
      expression in the ovary, leading to follicle rupture and oocyte release. Here we
      report the identification of endothelin-2 (EDN2) as a last moment-trigger of
      follicle rupture. In the ovary, EDN2 is exclusively and transiently expressed in
      the granulosa cells immediately before ovulation. Administration of EDN2 to the
      ovarian tissue induced rapid contraction, whereas addition of tezosentan, an
      endothelin receptor antagonist, diminishes the EDN2 effect. In vivo, treatment of
      tezosentan before ovulation substantially decreases gonadotropin-induced
      superovulation. As a target tissue of EDN2 action, we identified a layer of
      smooth muscle cells in the follicular wall of each follicle. Taken together, our
      data indicate that EDN2 induces follicular rupture by constricting periovulatory
      follicles.

PMID- 16410305
TI  - Central effects of calcitonin receptor-stimulating peptide-1 on energy
      homeostasis in rats.
AB  - The CT-R [calcitonin (CT) receptor] is expressed in the central nervous system
      and is involved in the regulation of food intake, thermogenesis, and behaviors.
      CT-R-stimulating peptide-1 (CRSP-1), a potent ligand for the CT-R, was recently
      isolated from the porcine brain. In this study, we first confirmed that porcine
      CRSP-1 (pCRSP-1) enhanced the cAMP production in COS-7 cells expressing
      recombinant rat CT-R, and then we examined the central effects of pCRSP-1 on
      feeding and energy homeostasis in rats. Intracerebroventricular (icv)
      administration of pCRSP-1 to free-feeding rats suppressed food intake in a dose
      dependent manner. Chronic icv infusion of pCRSP-1 suppressed body weight gain
      over the infusion period. Furthermore, icv administration of pCRSP-1 increased
      body temperature and decreased locomotor activity. The central effects of pCRSP-1
      were more potent than those of porcine CT in rats. In contrast, ip administration
      of pCRSP-1 did not elicit any anorectic or catabolic effects. Administration icv
      of pCRSP-1 also induced mild dyskinesia of the lower extremities and decreased
      gastric acid output. Fos expression induced by icv administration of pCRSP-1 was
      detected in the neurons of the paraventricular nucleus, dorsomedial hypothalamic
      nucleus, arcuate nucleus, locus coeruleus, and nucleus of solitary tract, areas
      that are known to regulate feeding and energy homeostasis. Administration icv of
      pCRSP-1 increased plasma concentrations of ACTH and corticosterone, implying that
      the hypothalamic-pituitary-adrenocortical axis might be involved in catabolic
      effects of pCRSP-1. These results suggest that CRSP-1 can function as a ligand
      for the CT-R and may act as a catabolic signaling molecule in the central nervous
      system.

PMID- 16410307
TI  - An aromatic environment in the vicinity of serine 281 is a structural requirement
      for thyrotropin receptor function.
AB  - The majority of constitutively activating human TSH receptor (hTSHR) mutations
      are located in the transmembrane helices as well as in the extracellular (ECLs)
      and intracellular loops. S(281) is one of two positions in the ectodomain in
      which activating hTSHR mutations have been identified in vivo (S(281)T, I, and
      N). To investigate the functional properties of this key residue in more detail,
      S(281) was replaced by each of the other 19 amino acids. Many substitutions led
      to constitutive receptor activation, suggesting that S(281) plays a pivotal role
      in maintaining the receptor in its inactive state. Strikingly, all substitutions
      with aromatic residues (S(281)W, F, Y, and H) show expression similar to that of
      wild-type hTSHR and are tolerated at this position because they maintain basal
      activity or express only slight constitutive activity. Three-dimensional modeling
      of the hTSHR suggested that S(281) and surrounding residues are in close
      proximity to ECL1. To investigate the possible importance of an aromatic
      environment between the ectodomain in the vicinity of S(281) and ECL1, aromatic
      residues Y(279), Y(476), H(478), Y(481), Y(482), and H(484) were replaced by
      alanine. Functional characterization showed impaired cell surface expression and
      signaling for Y(279)A and Y(481)A, in contrast to the other alanine mutants.
      However, substitutions of Y(279) and Y(481) with other aromatic residues
      exhibited surface expression and signaling comparable to wild-type hTSHR. Our
      results suggest that Y(279) in the extracellular domain and probably Y(481) in
      the ECL1 also are involved in an aromatic environment around S(281) in the hTSHR,
      which is important for functional receptor conformation and intramolecular
      receptor signaling.

PMID- 16410306
TI  - Aryl hydrocarbon receptor activation impairs cortisol response to stress in
      rainbow trout by disrupting the rate-limiting steps in steroidogenesis.
AB  - Anthropogenic stressors activating aryl hydrocarbon (Ah) receptor signaling,
      including polychlorinated biphenyls, impair the adaptive corticosteroid response
      to stress, but the mechanisms involved are far from clear. Using Ah receptor
      agonist (beta-naphthoflavone; BNF) and antagonist (resveratrol; RVT), we tested
      the hypothesis that steroidogenic pathway is a target for endocrine disruption by
      xenobiotics activating Ah receptor signaling. Trout (Oncorhynchus mykiss) were
      fed BNF (10 mg/kg.d), RVT (20 mg/kg.d) or a combination of both for 5 d, and
      subjected to a handling disturbance. BNF induced cytochrome P4501A1 expression in
      the interrenal tissue and liver, whereas this response was abolished by RVT,
      confirming Ah receptor activation. In control fish, handling disturbance
      transiently elevated plasma cortisol and glucose levels and transcript levels of
      interrenal steroidogenic acute regulatory protein (StAR), cytochrome P450
      cholesterol side chain cleavage (P450scc) and 11beta-hydroxylase over a 24-h
      period. BNF treatment attenuated this stressor-induced plasma and interrenal
      responses; these BNF-mediated responses were reverted back to the control levels
      in the presence of RVT. We further examined whether these in vivo impacts of BNF
      on steroidogenesis can be mimicked in vitro using interrenal tissue preparations.
      BNF depressed ACTH-mediated cortisol production, and this decrease corresponded
      with lower StAR and P450scc, but not 11beta-hydroxylase mRNA abundance. RVT
      eliminated this BNF-mediated depression of interrenal corticosteroidogenesis in
      vitro. Altogether, xenobiotics activating Ah receptor signaling are steroidogenic
      disruptors, and the mode of action includes inhibition of StAR and P450scc, the
      rate-limiting steps in steroidogenesis.

PMID- 16410308
TI  - Luteinizing hormone receptors translocate to plasma membrane microdomains after
      binding of human chorionic gonadotropin.
AB  - Receptor-mediated signal transduction by G protein-coupled receptors can involve
      redistribution of plasma membrane receptors into membrane structures that are
      characterized by insolubility in Triton X-100 and low buoyant density in sucrose
      gradients. Here we describe the translocation of wild-type (wt) rat LH receptors
      (LHR-wt) from the bulk membrane into membrane microdomains (rafts) after the
      binding of human chorionic gonadotropin (hCG). In sucrose gradient
      ultracentrifugation of plasma membranes from cells stably expressing FLAG-tagged
      LHR-wt, receptors were located in high-density membrane fractions before binding
      of hormone and in low-density fractions after hCG treatment. Receptor
      translocation to low-density sucrose fractions did not occur when cells were
      pretreated with 1% methyl-beta-cyclodextrin, which reduces membrane cholesterol
      and disrupts rafts. Single-particle tracking of individual FLAG-LHR-wt receptors
      showed that hCG-treated receptors become confined in small compartments with a
      diameter of 86 +/- 36 nm, significantly smaller than 230 +/- 79 nm diameter
      regions accessed by the untreated receptor. Receptors were no longer confined in
      these small compartments after disruption of rafts by methyl-beta-cyclodextrin, a
      treatment that also decreased levels of cAMP in response to hCG. Finally,
      translocation of LHR into rafts required a functional hormone-receptor complex
      but did not occur after extensive receptor cross-linking that elevated cAMP
      levels. Thus, retention of LHR in rafts or small membrane compartments is a
      characteristic of functional, hormone-occupied LHR-wt. Although raft
      translocation was not essential for cAMP production, it may be necessary for
      optimizing hormone-mediated signaling.

PMID- 16410309
TI  - Hyperinsulinemia, but not other factors associated with insulin resistance,
      acutely enhances colorectal epithelial proliferation in vivo.
AB  - The similarity in risk factors for insulin resistance and colorectal cancer (CRC)
      led to the hypothesis that markers of insulin resistance, such as elevated
      circulating levels of insulin, glucose, fatty acids, and triglycerides, are
      energy sources and growth factors in the development of CRC. The objective was
      thus to examine the individual and combined effects of these circulating factors
      on colorectal epithelial proliferation in vivo. Rats were fasted overnight,
      randomized to six groups, infused iv with insulin, glucose, and/or Intralipid for
      10 h, and assessed for 5-bromo-2-deoxyuridine labeling of replicating DNA in
      colorectal epithelial cells. Intravenous infusion of insulin, during a 10-h
      euglycemic clamp, increased colorectal epithelial proliferation in a dose
      dependent manner. The addition of hyperglycemia to hyperinsulinemia did not
      further increase proliferation. Intralipid infusion alone did not affect
      proliferation; however, the combination of insulin, glucose, and Intralipid
      infusion resulted in greater hyperinsulinemia than the infusion of insulin alone
      and further increased proliferation. Insulin infusion during a 10-h euglycemic
      clamp decreased total IGF-I levels and did not affect insulin sensitivity. These
      results provide evidence for an acute role of insulin, at levels observed in
      insulin resistance, in the proliferation of colorectal epithelial cells in vivo.

PMID- 16410310
TI  - Galanin-like peptide stimulates food intake via activation of neuropeptide Y
      neurons in the hypothalamic dorsomedial nucleus of the rat.
AB  - Galanin-like peptide (GALP), a 29-amino-acid neuropeptide, is located in the
      hypothalamic arcuate nucleus (ARC), binds to galanin receptor subtype 2, and
      induces food intake upon intracerebroventricular (icv) injection in rats.
      However, neural mechanisms underlying its orexigenic action remain unclear. We
      aimed to identify the nuclei and neuron species that mediate the food intake in
      response to icv GALP injection. Intracerebroventricular injection of GALP, as
      powerfully as that of neuropeptide Y (NYP), increased food intake for the initial
      2 h. GALP injected focally into the dorsomedial nucleus (DMN), but not the ARC,
      lateral hypothalamus, or paraventricular nucleus (PVN), stimulated food intake
      for 2 h after injection. In contrast, galanin injected into the DMN had no
      effect. DMN-lesion rats that received icv GALP injection showed attenuated
      feeding compared with control rats. Intracerebroventricular GALP injection
      increased c-Fos expression in NPY-containing neurons in the DMN, but not the ARC.
      GALP increased the cytosolic calcium concentration ([Ca(2+)](i)) in NPY
      immunoreactive neurons isolated from the DMN, but not the ARC. Furthermore, both
      anti-NPY IgG and NPY antagonists, when preinjected, counteracted the feeding
      induced by GALP injection. These data show that icv GALP injection induces a
      potent short-term stimulation of food intake mainly via activation of NPY
      containing neurons in the DMN.

PMID- 16410311
TI  - Computer simulation of the role of SOCS family protein in helper T cell
      differentiation.
AB  - The Th1/Th2 balance determines the nature of an immune response, and particular
      cytokines, IL-4 and IL-12, determine the direction at the initial stage of
      activation through TCRs. To investigate how cytokine networks and related
      signaling pathways impact upon the Th1/Th2 balance, we have developed a computer
      model for the simulation of Th differentiation. The model includes the IL-4, IL
      12 and IFN-gamma signal transduction pathways, a positive and negative feedback
      mechanism for cytokine signaling and cytokine-induced negative regulators such as
      suppressors of cytokine signaling (SOCS)1, SOCS3 and SOCS5. In the present study,
      we propose a 'Th0 model', in which naive T cells differentiate neither into Th1
      nor into Th2 states in unskewed cytokine conditions. The model was found to be
      consistent with experimental results in BALB/c mice. The results of in silico
      analysis in the condition with SOCS- and signal transducer and activator of
      transcription (STAT) family-deficient and transgenic states were well fitted to
      ex vivo experimental results for Th1 and Th2 differentiation profiles in the
      deficient and transgenic mice. The Th0 model suggested the possibility that
      dominant Th1 differentiation in STAT4/STAT6 double-deficient mice may be due to a
      positive feedback effect of initial IFN-gamma production from T cells. The in
      silico assessment of beneficial effects of inhibitory drugs by simulation
      analysis with our Th0 model indicated that Janus kinase 3-specific inhibitors
      might be suitable candidates for the modification of Th2-dominant immune
      responses. Our results demonstrate that models for the simulation of signaling
      network, such as our Th0 model, are useful tools for the in silico evaluation of
      novel drug candidates.

PMID- 16410312
TI  - A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node
      fibroblastic reticular cells has the potential to regulate T cell migration and
      adhesion.
AB  - Stromal cells in lymphoid tissues provide microenvironmental fields required for
      the triggering of efficient immune responses. Fibroblastic reticular cells (FRCs)
      are one of the integral constituents of such stromal fields; they construct the
      reticular network and are considered to regulate immune cells' behavior. However,
      the factors that mediate the interaction between lymphocytes and FRCs are poorly
      understood. Here we show that a mouse lymph node (LN)-derived FRC cell line,
      BLS4, expresses a transmembrane chemokine, CXC chemokine ligand (CXCL) 16, in
      response to tumor necrosis factor alpha (TNFalpha) and IFNgamma. TNFalpha-induced
      expression of CXCL16 depends on NFkappaB, p38 MAPK and PKA. Matrix
      metalloproteinase activity is required for producing soluble CXCL16 in the
      culture supernatant, likely via shedding at the juxtamembrane region of the
      extracellular domain. IL-12 enhances the expression of CXCR6 in anti-CD3/CD28
      stimulated CD8+ T cells and their adhesion to the BLS4 cell surface in a TNFalpha
      dependent fashion. The adherence is significantly inhibited in the presence of
      both anti-CXCL16 and anti-vascular cell adhesion molecule 1 (VCAM-1) antibodies.
      CXCL16 expression is also detected in the FRCs in LN sections and in gp38+VCAM-1+
      FRCs isolated from LNs. Taken together, these findings suggest that CXCL16 is an
      important mediator of lymphocyte-stromal interaction within lymphoid tissues.

PMID- 16410313
TI  - 2B4 (CD244), NTB-A and CRACC (CS1) stimulate cytotoxicity but no proliferation in
      human NK cells.
AB  - The recently described family of SLAM-related receptors plays an important role
      in the modulation of lymphocyte activity. The members of this family expressed on
      human NK cells are 2B4 (CD244), NTB-A and CRACC (CS1). The ligands of these
      surface receptors are also present on all human NK cells, suggesting that 2B4,
      NTB-A and CRACC are engaged during the contact of neighboring NK cells. Here we
      investigate the functional consequence of this interaction. We show that blocking
      the engagement of 2B4, NTB-A and CRACC has no effect on the proliferation or the
      development of the cytotoxic potential of human NK cells. However, triggering of
      2B4, NTB-A or CRACC by their physiological ligands on MHC class I-negative target
      cells induces potent NK cell cytotoxicity. This suggests that the engagement of
      inhibitory receptors by MHC class I on neighboring NK cells blocks 2B4-, NTB-A-
      and CRACC-induced NK cell cytotoxicity, thereby ensuring that NK cells do not
      kill each other. In support of this, limiting inhibitory receptor engagement by
      antibodies leads to the autologous killing of NK cells in a 2B4-, NTB-A- and
      CRACC-dependent manner.

PMID- 16410314
TI  - Involvement of IL-32 in activation-induced cell death in T cells.
AB  - NK cell transcript 4 (NK4), now denoted as IL-32, was originally identified as a
      transcript whose expression was increased in activated NK cells. It has been very
      recently demonstrated that NK4 is secreted from several cells upon the
      stimulation of some inflammatory cytokines such as IL-18, IL-1beta, IFN-gamma and
      IL-12. Furthermore, NK4 induces production of tumor necrosis factor, macrophage
      inflammatory protein (MIP)-2 and IL-8 in monocytic cell lines, indicating that
      this factor would be involved in the inflammatory responses. Based on these
      findings, NK4 was renamed IL-32. However, the biological activities of IL-32 on
      other cell types remained undetermined. Furthermore, it was still argued whether
      IL-32 acts on cells from outside or inside the cells. In this article, we first
      report that expression of IL-32 was up-regulated in activated T cells and NK
      cells, and that IL-32beta was the predominantly expressed isoform in activated T
      cells. IL-32 was specifically expressed in T cells undergoing apoptosis and
      enforced expression of IL-32-induced apoptosis, whereas its down-regulation
      rescued the cells from apoptosis in HeLa cells. IL-32 existing in the supernatant
      would be derived from the cytoplasm of apoptotic cells. These results strongly
      indicated that IL-32 would be involved in activation-induced cell death in T
      cells, probably via its intracellular actions. Our present findings expand our
      understanding of the biological function of IL-32 and argue that IL-32 may act on
      cells, not only from the outside but also from the inside.

PMID- 16410315
TI  - Interference with 3',5'-cyclic adenosine monophosphate response element binding
      protein stimulates apoptosis through aberrant cell cycle progression and
      checkpoint activation.
AB  - We previously reported that protein kinase A activity is an important determinant
      of thyroid cell survival. Given the important role of cAMP response element
      binding protein (CREB) in mediating the transcriptional effects of protein kinase
      A, we explored whether interference with CREB family members impaired thyroid
      cell survival. Expression of A-CREB, a dominant-negative CREB mutant that
      inhibits CREB DNA binding activity, induced apoptosis in rat thyroid cells. A
      CREB inhibited CRE-regulated gene expression but failed to alter the expression
      of bcl-2 family members or of well-characterized inhibitors of apoptosis. To
      elucidate the mechanism through which impaired CREB function triggered apoptosis,
      its effects on cell proliferation were examined. Expression of A-CREB inhibited
      cell number increases, in part due to delayed cell cycle transit. Protracted S
      phase progression in A-CREB-expressing cells was sufficient to activate a
      checkpoint response characterized by Chk-1, histone H2A.X, and p53
      phosphorylation. To determine whether cell cycle progression was required for
      apoptosis, the effects of p27 overexpression were investigated. Overexpression of
      p27 prevented cell cycle progression, checkpoint activation, and apoptosis in A
      CREB-expressing cells. These data reveal a novel mechanism through which
      interference with CREB abrogates cell survival, through checkpoint activation
      secondary to cell cycle delay. This study may explain how interference with CREB
      induces apoptosis in cells where alterations in the expression of pro- and anti
      survival genes are not detected.

PMID- 16410316
TI  - p38 mitogen-activated protein kinase stimulates estrogen-mediated transcription
      and proliferation through the phosphorylation and potentiation of the p160
      coactivator glucocorticoid receptor-interacting protein 1.
AB  - Nuclear hormone receptors, such as the estrogen receptors (ERs), are regulated by
      specific kinase signaling pathways. Here, we demonstrate that the p38 MAPK
      stimulates both ERalpha- and ERbeta-mediated transcription in MCF-7 breast
      carcinoma, Ishikawa endometrial adenocarcinoma, and human embryonic kidney 293
      cells. Inhibition of this potentiation using the p38 inhibitor, RWJ67657, blocked
      estrogen-mediated transcription and proliferation. Activated ERs promote gene
      expression in part through the recruitment of the p160 class of coactivators.
      Because no direct p38 phosphorylation sites have been determined on either
      ERalpha or beta, we hypothesized that p38 could target the p160 class of
      coactivators. We show for the first time using pharmacological and molecular
      techniques that the p160 coactivator glucocorticoid receptor-interacting protein
      1 (GRIP1) is phosphorylated and potentiated by the p38 MAPK signaling cascade in
      vitro and in vivo. S736 was identified as a necessary site for p38 induction of
      GRIP1 transcriptional activation. The C terminus of GRIP1 was also demonstrated
      to contain a p38-responsive region. Taken together, these results indicate that
      p38 stimulates ER-mediated transcription by targeting the GRIP1 coactivator.

PMID- 16410317
TI  - LAMARC 2.0: maximum likelihood and Bayesian estimation of population parameters.
AB  - We present a Markov chain Monte Carlo coalescent genealogy sampler, LAMARC 2.0,
      which estimates population genetic parameters from genetic data. LAMARC can co
      estimate subpopulation Theta = 4N(e)mu, immigration rates, subpopulation
      exponential growth rates and overall recombination rate, or a user-specified
      subset of these parameters. It can perform either maximum-likelihood or Bayesian
      analysis, and accomodates nucleotide sequence, SNP, microsatellite or
      elecrophoretic data, with resolved or unresolved haplotypes. It is available as
      portable source code and executables for all three major platforms. AVAILABILITY:
      LAMARC 2.0 is freely available at http://evolution.gs.washington.edu/lamarc

PMID- 16410318
TI  - Maximum likelihood estimates of allele frequencies and error rates from samples
      of related individuals by gene counting.
AB  - SUMMARY: Graphical modeling is used to extend the gene counting method to compute
      maximum likelihood estimates of allele frequencies for samples of individuals
      related in extended pedigrees. Genotypes may be missing or partially observed,
      and error rates can be simultaneously estimated. AVAILABILITY: The Java classes
      and Javadocs pages for ?mathsf?hbox GeneCountAlleles can be obtained from
      bioinformatics.med.utah.edu/~alun, which also has more information on its use and
      file formats.

PMID- 16410319
TI  - Hierarchical multi-label prediction of gene function.
AB  - MOTIVATION: Assigning functions for unknown genes based on diverse large-scale
      data is a key task in functional genomics. Previous work on gene function
      prediction has addressed this problem using independent classifiers for each
      function. However, such an approach ignores the structure of functional class
      taxonomies, such as the Gene Ontology (GO). Over a hierarchy of functional
      classes, a group of independent classifiers where each one predicts gene
      membership to a particular class can produce a hierarchically inconsistent set of
      predictions, where for a given gene a specific class may be predicted positive
      while its inclusive parent class is predicted negative. Taking the hierarchical
      structure into account resolves such inconsistencies and provides an opportunity
      for leveraging all classifiers in the hierarchy to achieve higher specificity of
      predictions. RESULTS: We developed a Bayesian framework for combining multiple
      classifiers based on the functional taxonomy constraints. Using a hierarchy of
      support vector machine (SVM) classifiers trained on multiple data types, we
      combined predictions in our Bayesian framework to obtain the most probable
      consistent set of predictions. Experiments show that over a 105-node subhierarchy
      of the GO, our Bayesian framework improves predictions for 93 nodes. As an
      additional benefit, our method also provides implicit calibration of SVM margin
      outputs to probabilities. Using this method, we make function predictions for
      multiple proteins, and experimentally confirm predictions for proteins involved
      in mitosis. SUPPLEMENTARY INFORMATION: Results for the 105 selected GO classes
      and predictions for 1059 unknown genes are available at:
      http://function.princeton.edu/genesite/ CONTACT: ogt@cs.princeton.edu.

PMID- 16410320
TI  - Comparison of Affymetrix GeneChip expression measures.
AB  - MOTIVATION: In the Affymetrix GeneChip system, preprocessing occurs before one
      obtains expression level measurements. Because the number of competing
      preprocessing methods was large and growing we developed a benchmark to help
      users identify the best method for their application. A webtool was made
      available for developers to benchmark their procedures. At the time of writing
      over 50 methods had been submitted. RESULTS: We benchmarked 31 probe set
      algorithms using a U95A dataset of spike in controls. Using this dataset, we
      found that background correction, one of the main steps in preprocessing, has the
      largest effect on performance. In particular, background correction appears to
      improve accuracy but, in general, worsen precision. The benchmark results put
      this balance in perspective. Furthermore, we have improved some of the original
      benchmark metrics to provide more detailed information regarding precision and
      accuracy. A handful of methods stand out as providing the best balance using
      spike-in data with the older U95A array, although different experiments on more
      current arrays may benchmark differently. AVAILABILITY: The affycomp package, now
      version 1.5.2, continues to be available as part of the Bioconductor project
      (http://www.bioconductor.org). The webtool continues to be available at
      http://affycomp.biostat.jhsph.edu CONTACT: rafa@jhu.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 16410321
TI  - Chemical effects in biological systems (CEBS) object model for toxicology data,
      SysTox-OM: design and application.
AB  - MOTIVATION: The CEBS data repository is being developed to promote a systems
      biology approach to understand the biological effects of environmental stressors.
      CEBS will house data from multiple gene expression platforms (transcriptomics),
      protein expression and protein-protein interaction (proteomics), and changes in
      low molecular weight metabolite levels (metabolomics) aligned by their detailed
      toxicological context. The system will accommodate extensive complex querying in
      a user-friendly manner. CEBS will store toxicological contexts including the
      study design details, treatment protocols, animal characteristics and
      conventional toxicological endpoints such as histopathology findings and clinical
      chemistry measures. All of these data types can be integrated in a seamless
      fashion to enable data query and analysis in a biologically meaningful manner.
      RESULTS: An object model, the SysBio-OM (Xirasagar et al., 2004) has been
      designed to facilitate the integration of microarray gene expression, proteomics
      and metabolomics data in the CEBS database system. We now report SysTox-OM as an
      open source systems toxicology model designed to integrate toxicological context
      into gene expression experiments. The SysTox-OM model is comprehensive and
      leverages other open source efforts, namely, the Standard for Exchange of
      Nonclinical Data (http://www.cdisc.org/models/send/v2/index.html) which is a data
      standard for capturing toxicological information for animal studies and Clinical
      Data Interchange Standards Consortium
      (http://www.cdisc.org/models/sdtm/index.html) that serves as a standard for the
      exchange of clinical data. Such standardization increases the accuracy of data
      mining, interpretation and exchange. The open source SysTox-OM model, which can
      be implemented on various software platforms, is presented here. AVAILABILITY: A
      universal modeling language (UML) depiction of the entire SysTox-OM is available
      at http://cebs.niehs.nih.gov and the Rational Rose object model package is
      distributed under an open source license that permits unrestricted academic and
      commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads.
      Currently, the public toxicological data in CEBS can be queried via a web
      application based on the SysTox-OM at http://cebs.niehs.nih.gov CONTACT:
      xirasagars@saic.com SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 16410322
TI  - LSAT: learning about alternative transcripts in MEDLINE.
AB  - MOTIVATION: Generation of alternative transcripts from the same gene is an
      important biological event due to their contribution in creating functional
      diversity in eukaryotes. In this work, we choose the task of extracting
      information around this complex topic using a two-step procedure involving
      machine learning and information extraction. RESULTS: In the first step, we
      trained a classifier that inductively learns to identify sentences about
      physiological transcript diversity from the MEDLINE abstracts. Using a large hand
      built corpus, we compared the sentence classification performance of various text
      categorization methods. Support vector machines (SVMs) followed by the maximum
      entropy classifier outperformed other methods for the sentence classification
      task. The SVM with the radial basis function kernel and optimized parameters
      achieved Fbeta-measure of 91% during the 4-fold cross validation and of 74% when
      applied to all sentences in more than 12 million abstracts of MEDLINE. In the
      second step, we identified eight frequently present semantic categories in the
      sentences and performed a limited amount of semantic role labeling. The role
      labeling step also achieved very high Fbeta-measure for all eight categories.
      AVAILABILITY: The results of our two-step procedure are summarized in the LSAT
      database of alternative transcripts. LSAT is available at
      http://www.bork.embl.de/LSAT CONTACT: shah@embl.de SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 16410323
TI  - Tools for the SBML Community.
AB  - MOTIVATION: SBML is quickly becoming the standard format to exchange biochemical
      models. The tools presented in this paper are loosely-coupled, and are intended
      to be incorporated into SBML aware applications. The rationale for this is to
      reduce the amount of repeated work carried out within the community and to create
      tools that offer a greater number of features to the end-user. AVAILABILITY: All
      tools described are available from http://www.basis.ncl.ac.uk/software and are
      licensed under GNU General Public License.

PMID- 16410324
TI  - OrthologID: automation of genome-scale ortholog identification within a parsimony
      framework.
AB  - MOTIVATION: The determination of gene orthology is a prerequisite for mining and
      utilizing the rapidly increasing amount of sequence data for genome-scale
      phylogenetics and comparative genomic studies. Until now, most researchers use
      pairwise distance comparisons algorithms, such as BLAST, COG, RBH, RSD and
      INPARANOID, to determine gene orthology. In contrast, orthology determination
      within a character-based phylogenetic framework has not been utilized on a
      genomic scale owing to the lack of efficiency and automation. RESULTS: We have
      developed OrthologID, a Web application that automates the labor-intensive
      procedures of gene orthology determination within a character-based phylogenetic
      framework, thus making character-based orthology determination on a genomic scale
      possible. In addition to generating gene family trees and determining orthologous
      gene sets for complete genomes, OrthologID can also identify diagnostic
      characters that define each orthologous gene set, as well as diagnostic
      characters that are responsible for classifying query sequences from other
      genomes into specific orthology groups. The OrthologID database currently
      includes several complete plant genomes, including Arabidopsis thaliana, Oryza
      sativa, Populus trichocarpa, as well as a unicellular outgroup, Chlamydomonas
      reinhardtii. To improve the general utility of OrthologID beyond plant species,
      we plan to expand our sequence database to include the fully sequenced genomes of
      prokaryotes and other non-plant eukaryotes. AVAILABILITY:
      http://nypg.bio.nyu.edu/orthologid/

PMID- 16410325
TI  - Automated discovery of 3D motifs for protein function annotation.
AB  - MOTIVATION: Function inference from structure is facilitated by the use of
      patterns of residues (3D motifs), normally identified by expert knowledge, that
      correlate with function. As an alternative to often limited expert knowledge, we
      use machine-learning techniques to identify patterns of 3-10 residues that
      maximize function prediction. This approach allows us to test the assumption that
      residues that provide function are the most informative for predicting function.
      RESULTS: We apply our method, GASPS, to the haloacid dehalogenase, enolase,
      amidohydrolase and crotonase superfamilies and to the serine proteases. The
      motifs found by GASPS are as good at function prediction as 3D motifs based on
      expert knowledge. The GASPS motifs with the greatest ability to predict protein
      function consist mainly of known functional residues. However, several residues
      with no known functional role are equally predictive. For four groups, we show
      that the predictive power of our 3D motifs is comparable with or better than
      approaches that use the entire fold (Combinatorial-Extension) or sequence
      profiles (PSI-BLAST). AVAILABILITY: Source code is freely available for academic
      use by contacting the authors. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 16410326
TI  - Towards defining parameters for a successful single embryo transfer in frozen
      cycles.
AB  - BACKGROUND: Twin pregnancies in IVF should be avoided by transferring embryos one
      at a time, even for frozen cycles. In this study, we investigated the effect of
      blastomere lysis and cleavage in singleton frozen embryo transfer (sFET) cycles.
      Outcomes were compared with the transfer of two embryos in frozen transfer cycles
      (dFET). METHODS: A retrospective analysis was performed on 891 FET cycles,
      involving 404 sFET and 487 dFET cycles. RESULTS: Overall, in sFET cycles, the
      pregnancy and implantation rates were 8.9 and 8.7%. When blastomere lysis was
      more than 25% but no greater than 50%, the pregnancy and implantation rates were
      3.2%. If blastomere lysis was greater than 50% there were no pregnancies. If
      blastomere lysis was less than 25%, but with no cleavage, the pregnancy and
      implantation rates were 4.1%. The results significantly improved (P = 0.007) in
      the group with less than 25% lysis, when cleavage occurred. The pregnancy and
      implantation rates for this group were 17.3 and 16.6%. This was not significantly
      different from unselected two embryo transfers (22 and 12.7%,P = 0.2 and 0.19,
      respectively). There were 21 twins with dFET (19.6% of pregnancies) and none in
      sFET. CONCLUSION: Both blastomere lysis and cleavage affect the outcome in sFET.
      To avoid the risk of twins, sFET should be considered when the embryo shows less
      than 25% blastomere lysis and at least one blastomere cleaves.

PMID- 16410327
TI  - Stellate transformation of invasive trophoblast: a distinct phenotype of
      trophoblast that is involved in decidual vascular remodelling and controlled
      invasion during pregnancy.
AB  - BACKGROUND: Successful implantation relies on the tightly regulated invasion of
      extravillous trophoblasts (EVTs). However, little is known about their phenotypic
      differentiation and relevant motile behaviour. Furthermore, the cell-cell
      interactions between EVTs and decidual arterioles during physiological
      transformation are also poorly understood. METHODS: A total of 128 decidual
      specimens from early and late gestations containing components of EVTs and spiral
      arterioles were investigated using immunohistochemistry and periodic acid-Schiff
      reaction. RESULTS: Unipolar, tadpole-like EVTs are observed throughout the
      interstitial area, with a tendency to decrease along the invasive pathway. The
      stellate differentiation of the EVTs is identified around and inside decidual
      arterioles or in the third-trimester myometrium. Furthermore, stellate
      transformation of EVTs precedes its interactions with the decidual arteriole.
      These specialized stellate trophoblasts invade and infiltrate the tunica media,
      accompanying lacuna formation inside the vessel wall and perturbation of actin
      fibre alignment of the tunica media. CONCLUSION: Stellate transformation of
      trophoblasts may explain controlled invasion of EVTs and probably plays a key
      role in initiating cell-cell interaction in decidual vascular remodelling.

PMID- 16410328
TI  - A randomized clinical trial of the effects of isosorbide mononitrate on bone
      formation and resorption in post-menopausal women: a pilot study.
AB  - BACKGROUND: Nitric oxide (NO) stimulates bone formation and inhibits bone
      resorption in vitro. NO donors (nitrates) are inexpensive and widely available,
      but their value for post-menopausal osteoporosis has never been evaluated in a
      randomized trial. The objective of this study was to compare the effects of 5 and
      20 mg of isosorbide mononitrate (ISMO) on markers of bone turnover in post
      menopausal women. METHODS: A prospective randomized trial was carried out in the
      Department of Obstetrics & Gynecology, Ain Shams University, Egypt. The study
      included 50 healthy post-menopausal women with a hip bone mineral density T score
      between 0 and -2.5. Participants were randomly assigned to 5 or 20 mg/day of ISMO
      for 12 weeks. Urine N-telopeptide (NTx), a marker of bone resorption, and serum
      bone-specific alkaline phosphatase (BSALP), a marker of bone formation, were
      measured. Markers were measured immediately before randomization and after 12
      weeks of treatment. The percent change in NTx and BSALP for each of the treatment
      groups (5 mg ISMO and 20 mg ISMO) was calculated. The main outcome measures were
      serum NTx and BSALP in the 5 and 20 mg ISMO groups after 12 weeks of treatment.
      RESULTS: Women adhering to 20 mg of ISMO had a 42.03% (95% confidence interval
      (CI), 20.1-73.7) reduction in NTx and a 29.05% (95% CI, 10.8-48.4) increase in
      BSALP, and women adhering to 5 mg of ISMO had a 31.12% (95% CI, 8.3-68.2)
      reduction in NTx and a 28.4% (95% CI, 4.6-52.1) increase in BSALP. CONCLUSION:
      ISMO, as a NO donor, may be useful for the prevention of post-menopausal
      osteoporosis.

PMID- 16410329
TI  - Evidence of a high proportion of premature unbalanced separation of sister
      chromatids in the first polar bodies of women of advanced age.
AB  - BACKGROUND: Maternal ageing is the only aetiological factor unequivocally linked
      to aneuploidy. Two mechanisms seem to explain these abnormalities in oocytes: non
      disjunction and premature unbalanced separation of sister chromatids (PSSC).
      Previous studies of unfertilized oocytes argue for a major role of PSSC in the
      aetiology of aneuploidy for women of advanced age, but in vitro ageing of the
      oocytes could influence the results. METHODS: Owing to the high prevalence of
      aneuploidy in women of advanced age, chromosomal screening of the first polar
      body just before ICSI was offered to women (from 38 years of age) included in an
      assisted reproduction programme. RESULTS: Among 141 oocytes from 29 women (mean
      age 40 years and 2 months), 43 (30.5%) were abnormal. Sixty-five abnormalities
      were found and PSSC was involved in 80% of cases. CONCLUSION: These results are
      in accordance with previous studies and confirm, in 'fresh' oocytes, the major
      role of PSSC in the aetiology of aneuploidy in women of advanced age.

PMID- 16410330
TI  - Assessment of the ovarian volume, number and volume of follicles and ovarian
      vascularity by three-dimensional ultrasonography and power Doppler angiography on
      the HCG day to predict the outcome in IVF/ICSI cycles.
AB  - OBJECTIVE: The aim of this prospective study was to investigate whether ovarian
      blood flow is related to embryological parameters and whether it could be a
      predictor of outcomes of IVF/ICSI. METHODS: Eighty infertile women underwent
      ovarian stimulation with gonadotrophins after a long protocol with GnRH agonists.
      The ovarian volume (OV), number of follicles (NF) and follicular volume (FV) of
      all follicles >10 mm and vascularization index (VI), flow index (FI) and
      vascularization-flow index (VFI) were obtained by three-dimensional (3D)
      ultrasonography and power Doppler angiography (PDA) on the day of HCG
      administration. These parameters were tested for their relation with IVF
      laboratory parameters. RESULTS: The OV, FV, VI, FI and VFI were significantly
      greater in the pregnant group. The NF and FV were the only independent predictors
      of the number of oocytes retrieved, mature and fertilized, and the number of
      embryos developed and their cumulative embryo score. Nevertheless, the number of
      grade 1 embryos depends on the NF and the VI. The ovarian FI and the number of
      transferred grade 1 embryos can predict gestation in 76% of IVF patients. A low
      FI and non-grade 1 embryo transferred are also associated with an increased
      pregnancy loss. CONCLUSION: 3D ultrasonography and PDA allow for an easier
      ovarian assessment in IVF cycles. The predictive value of IVF outcome suggests a
      high clinical usefulness of this new technique.

PMID- 16410331
TI  - Factors affecting time to pregnancy.
AB  - BACKGROUND: Both lifestyle factors and occupational and environmental factors
      have been suggested to affect the female reproductive system. In the present
      study, the separate and joint effects of several such factors are investigated.
      METHODS: Information on time to pregnancy (TTP) was available for 1578 women
      randomly selected from the general Swedish population. The information was
      collected retrospectively by using self-administered questionnaires. By means of
      logistic regression of survival data, fecundability odds ratios were determined
      for many factors. Multivariate models were used to determine which factors had
      the most impact on TTP. RESULTS: Several lifestyle factors were found to
      associate with TTP. However, only use of oral contraceptives prior to attempting
      to conceive, menstrual cycle length, age at conception and parity remained in the
      multivariate models. Together, these factors explained 14% of the variance in
      TTP. Excluding first and second month conceptions, only age at conception and
      menstrual cycle length remained in the multivariate models, together explaining
      only 8% of the variance in TTP. CONCLUSIONS: Although information on several
      factors was available, the multivariate model explained only a small fraction of
      the variation in the observed time to pregnancies. Furthermore, female biological
      factors seemed more important predictors of TTP than lifestyle factors.

PMID- 16410332
TI  - Comparative assessment of pre- and post-donation attitudes towards potential
      oocyte and embryo disposition and management among ovum donors in an oocyte
      donation programme.
AB  - BACKGROUND: In anonymous oocyte donation programmes, the disposition of retrieved
      oocytes and subsequent embryo management are at the discretion of the IVF
      programme and the oocyte recipients, as donors waive all rights following their
      donation. Nonetheless, donors are routinely made aware of ways in which oocytes
      and resulting embryos may be used and elect to proceed with the process even in
      the presence of reservations to some clinical scenarios before their donation.
      The aim of our study was to examine oocyte donors' attitudes to oocyte and embryo
      disposition and management and how initial reservations change over the course of
      the donation process. METHODS: Oocyte donors in a university-based IVF programme
      were asked about their willingness to donate in relation to various clinical
      scenarios during the initial screening interview and at the post-donation exit
      interview. Results were tabulated as 'yes' or 'no'. RESULTS: At the pre-donation
      interview, 72% of donor candidates expressed reservations to one or more clinical
      scenarios. More reservations were expressed at the post-donation interview
      compared with the pre-donation interview. The greatest reservations were donating
      to recipients >50 years of age (P < 0.05). Despite this, 97% of donors were
      willing to donate again. CONCLUSION: Oocyte donors' attitudes towards various
      clinical scenarios changed following their donation, reflecting overall greater
      reservations following the donation process. Although speculative, donors may be
      more willing to assert their opinions or donor attitudes become more restrictive.

PMID- 16410333
TI  - Prioritizing IVF patients according to the number of existing children--a
      proposed refinement to the current guideline.
AB  - The National Health Service is poised to offer at least one cycle of IVF
      treatment to couples free of charge in the UK, provided that certain clinical
      criteria are met. At a local level, therefore, funders are faced with the problem
      of prioritizing patients and establishing waiting lists. It is generally accepted
      that preference should be given to those with the 'greatest need', but it is
      uncertain what the criterion is for greatest need. We propose two recommendations
      as a modification to the current guideline that stresses the need to favour
      'couples who do not have any children living with them'. First, we suggest that
      parental responsibility rather than shared residence be used as a criterion for
      eligibility. Second, we present a need-based approach that can be used coherently
      to distribute publicly funded treatment. In an attempt to achieve a fair way of
      prioritizing patients, we make distinctions between different family
      arrangements, based on the number of existing children. Our approach treats like
      cases alike, and ranks different cases relative to each other in a manner that is
      equitable and charitable.

PMID- 16410334
TI  - Pregnancy and live birth after focused ultrasound surgery for symptomatic focal
      adenomyosis: a case report.
AB  - Adenomyosis is a benign disease whose symptoms mimic those of uterine leiomyoma.
      Hysterectomy is the treatment of choice; conservative surgery is difficult to
      perform and can damage the uterine structural integrity. We report the case of a
      36-year-old woman who had difficulty conceiving because of profuse
      menometrorrhagia. An 84 cm3 uterine tumour was diagnosed on ultrasonography as
      leiomyoma, and conservative myomectomy was planned. Magnetic resonance imaging
      (MRI) corrected the diagnosis to focal adenomyosis. Magnetic resonance-guided
      focused ultrasound surgery (MRgFUS) destroyed a significant part of the tumour.
      Following an uncomplicated MRgFUS treatment, a non-perfused volume of 33 cm3 was
      measured. At 6 weeks, the patient experienced a significant reduction in
      menometrorrhagia and a marked decrease in tumour size (about 50%). She conceived
      spontaneously and, after an uneventful pregnancy, gave birth at term to a healthy
      infant via normal vaginal delivery. No structural uterine abnormality was
      detected after her delivery. This report highlights the difficult diagnosis and
      new therapeutic considerations of adenomyosis. MRgFUS seems to have the potential
      to precisely and effectively treat focal adenomyosis without damage to
      surrounding healthy myometrium, allowing for normal reproduction. Further studies
      are needed to assess the overall safety and long-term effectiveness of MRgFUS for
      the non-invasive treatment of adenomyosis.

PMID- 16410335
TI  - Histological classification of chorionic villous vascularization in early
      pregnancy.
AB  - BACKGROUND: The objective of the study was to assess the reproducibility of a new
      classification for early pregnancy chorionic villous vascularization (Grade: I,
      normal; IIA, mild hypoplasia; IIB, severe hypoplasia and III, avascular) for
      routine microscopic examination in daily clinical practice. METHODS: In this
      observational study, four observers scored first trimester chorionic villous
      vascularization. Scoring was performed in microscopic slides of chorionic tissue
      obtained by D&C in 30 patients with early pregnancy loss due to empty sac (n =
      10), fetal death (n = 10) and termination of pregnancy (n = 10) using the new
      classification. Ultrasonographic measurement of trophoblastic thickness (TT) at
      the implantation site was available in all patients and in a reference group of
      100 ongoing singleton pregnancies. The vascularization score could therefore be
      related to the TT. RESULTS: The new classification resulted in a good-to
      excellent agreement in histological scoring (0.73-0.90) between investigators
      (kappa 0.64-0.86). TT was not related to either vascularization or pregnancy
      outcome and only partly to hydropic degeneration. CONCLUSION: The vascularization
      scoring system is a simple, valid and effective method for assessment of
      chorionic villous vascularization. It is helpful in understanding the underlying
      cause of pregnancy loss, as the classification can distinguish between normal and
      abnormal embryonic development. We did not find either a relation between TT and
      pregnancy outcome or between TT and vascularization.

PMID- 16410336
TI  - Follow-up study of two sisters with type A syndrome of severe insulin resistance
      gives a new insight into PCOS pathogenesis in relation to puberty and pregnancy
      outcome: a case report.
AB  - We report two sisters with profound insulin resistance associated with a novel
      heterozygous missense mutation in exon 19 (His1130Arg) of the insulin receptor
      gene. The eldest was seen after puberty at age 15 and she presented a severe form
      of polycystic ovary syndrome (PCOS) with biological hyperandrogenism (HA)
      mimicking a virilizing tumour. However, she has been able to ovulate under
      clomiphene citrate (CC) and to achieve two uneventful pregnancies. The patient
      had no glucose tolerance abnormality during pregnancies. The outcome of pregnancy
      was good except for a low birthweight. The youngest sister was seen earlier in
      life (at age 11) before puberty. First, she developed polycystic ovaries (PCO),
      seen under ultrasound scan, and later also developed full PCOS. This second
      finding gave us the opportunity to observe that PCO developed before and at the
      beginning of puberty despite low LH levels. We postulate that the development of
      PCO was the consequence of an LH-independent intra-ovarian HA likely induced by
      the severe hyperinsulinism in the context of genetic abnormalities.

PMID- 16410337
TI  - Removal of a residual portion of a uterine septum in women of advanced
      reproductive age: obstetric outcome.
AB  - BACKGROUND: To learn more about the obstetric outcome after initial septum
      resection and remnant septum (< or =1 cm) resection. METHODS: In 94 patients with
      septate uteri who underwent uterine septum resection, the reproductive efficiency
      was analysed in a prospective observational study. The reproductive outcome was
      analysed after initial resection and (if required) consecutive procedures.
      RESULTS: A total of 94 women were enrolled in the study; all had had two or more
      miscarriages. The septum was completely removed during the first hysteroscopy in
      58 (62%) cases. A residual septum was observed in 36 (38%) patients. Subsequent
      operative hysteroscopy was performed in the cases (29/36; 80.5%) involving
      repeated miscarriage and unsuccessful conception. The minimum observation time
      was 24 months. The difference in delivery rate after the first hysteroscopy
      between those with a normalized uterine cavity (26/58; 44.8%) and those with
      remnants (7/36; 19.4%) was statistically significant (P < 0.05). In fact,
      following the normalization of the uterine cavity, 62.1% (18/29) of the patients
      delivered, as compared with 19.4% of those (7/36) with a residue and Kaplan-Meyer
      curves revealed a statistically significant difference (P < 0.05). CONCLUSIONS:
      Women with a remnant uterine septum have an increased chance of successful
      pregnancy with an improved obstetric outcome after normalization of the uterine
      cavity.

PMID- 16410338
TI  - What about the remaining twins since single-embryo transfer? How far can (should)
      we go?
AB  - Single-embryo transfer (SET) and more specifically elective SET (eSET) have taken
      their place in good clinical IVF/ICSI practice. After the initial cautious search
      for the characteristics of the twin-prone patient and of the selection of the
      embryo with the highest implantation potential many centres have embarked on the
      (progressive) implementation of SET, either by conviction or forced by
      legislation or both. It was only because the ongoing pregnancy rates remained
      largely unaffected that SET was accepted. Generally speaking, it can be said that
      the twinning rate after IVF/ICSI has dropped by at least 50% simply by
      transferring only one good-quality embryo in the first and second fresh IVF/ICSI
      cycles in young women, without decrease in the overall pregnancy rate. Preventing
      'the second half' of IVF/ICSI twins constitutes another and probably tougher
      challenge because the target group is a heterogeneous mix consisting of patients
      in very different clinical situations. Can we expand our experience for further
      twin prevention to women of older age and to cycles of higher rank without a
      significant drop in pregnancy rates? Can we extend it to more cryopreservation
      cycles? To have an idea of future target groups for increased application of SET,
      we analysed the remaining twins after double-embryo transfer (DET), and from
      these data we suggest expanding the eSET policy to women <38 years of age until
      the third cycle and to cryopreservation cycles.

PMID- 16410339
TI  - Cardiac troponin T circulates in the free, intact form in patients with kidney
      failure.
AB  - BACKGROUND: The clinical significance of the increased concentrations of cardiac
      troponins observed in patients with end stage renal disease (ESRD) in the absence
      of an acute coronary syndrome (ACS) is controversial. One proposed explanation is
      that immunoreactive fragments of cardiac troponin T (cTnT) accumulate in ESRD. We
      used gel-filtration chromatography (GFC) to ascertain whether fragments of cTnT,
      which could cross-react in the commercial diagnostic immunoassay (Roche
      Diagnostics), were the cause of the increased cTnT in the serum of patients with
      ESRD. METHODS: We subjected sera from ESRD patients (n = 21) receiving dialysis
      and having increased cTnT concentrations to size-separation GFC. We detected cTnT
      in the chromatography fractions by use of the same antibodies used in the
      commercial assay for serum cTnT. RESULTS: In all patients, cTnT immunoreactivity
      eluted as a major, homogeneous peak in an identical position between the peaks of
      serum prolactin [relative molecular mass (Mr) 23,000] and albumin (Mr 67,000):
      the elution pattern of cTnT in samples obtained from ACS patients was identical
      to that of the ESRD patients. There was no evidence that low-molecular-mass (Mr <
      23,000) cTnT fragments were the cause of the increased cTnT in the patients
      studied. CONCLUSIONS: The form of cTnT observed in the serum of patients with
      kidney failure and immunoreactive in the diagnostic assay is predominantly the
      free intact form, as in patients with ACS. Our data are consistent with the view
      that circulating cTnT in renal failure reflects cardiac pathology.

PMID- 16410340
TI  - Minimal disease detection and confirmation in hematologic malignancies: combining
      cell sorting with clonality profiling.
AB  - BACKGROUND: In this study we demonstrate the technical application of flow
      cytometry and cell sorting combined with gene-rearrangement clonality profiling
      to detect and confirm minimal disease in 2 leukemia and 2 lymphoma cases.
      METHODS: Specimens with low percentages (0.05%-5%) of abnormal lymphoid
      populations were identified by flow cytometry. The abnormal lymphoid populations
      were sorted by flow cytometry, and the purified tumor populations along with
      unsorted fractions were subsequently analyzed for the presence of clonal gene
      rearrangements by PCR and fluorescence-based capillary electrophoresis fragment
      analysis. RESULTS: In 3 cases, distinct clonality profiles could be detected in
      the purified tumor cell fraction, and suspicious amplicons of identical sizes
      were detected among the polyclonal backgrounds in the unsorted specimens. For 1
      patient, a monoclonal signal was detected in the sorted tumor cell fraction but
      not in the unseparated bone marrow specimen containing 0.05% abnormal
      lymphoblasts. A subsequent bone marrow specimen containing 4.8% recurring
      leukemia cells tested positive with a clonality profile that matched the previous
      profile in the sorted cell population. CONCLUSIONS: The described method
      integrating 2 technologies allows genotypic confirmation of an aberrant
      population detected by immunophenotype to increase diagnostic certainty. This
      strategy provides a sensitive tool for disease monitoring without the need for
      patient-specific primer design and assay optimization required for quantitative
      PCR analysis.

PMID- 16410341
TI  - Serum tumor markers in breast cancer: are they of clinical value?
AB  - BACKGROUND: Although multiple serum-based tumor markers have been described for
      breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen
      (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2
      (the extracellular domain), the most widely used are CA 15-3 and CEA. METHODS:
      The literature relevant to serum tumor markers in breast cancer was reviewed.
      Particular attention was given to systematic reviews, prospective randomized
      trials, and guidelines issued by expert panels. RESULTS: Because of a lack of
      sensitivity for early disease and lack of specificity, none of the available
      markers is of value for the detection of early breast cancer. High preoperative
      concentrations of CA 15-3 are, however, associated with adverse patient outcome.
      Although serial determinations of tumor markers after primary treatment for
      breast cancer can preclinically detect recurrent/metastatic disease with lead
      times of approximately 2-9 months, the clinical value of this lead time remains
      to be determined. Serum markers, however, are the only validated approach for
      monitoring treatment in patients with advanced disease that cannot be evaluated
      by use of conventional criteria. CONCLUSIONS: CA 15-3 is one of the first
      circulating prognostic factors for breast cancer. Preoperative concentrations
      thus might be combined with existing prognostic factors for predicting outcome in
      patients with newly diagnosed breast cancer. At present, the most important
      clinical application of CA 15-3 is in monitoring therapy in patients with
      advanced breast cancer that is not assessable by existing clinical or radiologic
      procedures.

PMID- 16410342
TI  - Calculating uncertainty of measurement for serology assays by use of precision
      and bias.
AB  - BACKGROUND: In many countries, regulatory authorities that use International
      Organization for Standardization Standards to assess laboratory competence
      require an estimate of the uncertainty of measurement (MU) of assay test results.
      This estimate can be determined by identifying all sources of variation,
      calculating the extent of variation, and using established methods to combine the
      uncertainty. Alternatively, laboratory staff may use existing data generated from
      evaluations, proficiency testing, or external run controls to determine MU.
      METHODS: A quality-control (QC) sample with low reactivity was tested by
      laboratories participating in a national QC program. The results of testing the
      QC sample were entered into a shared database by use of an Internet-based
      program, EDCNet. Using a statistical approach that accounts for imprecision and
      bias of test results, we estimated the MU of the laboratories. RESULTS: A total
      of 2167 test results of a single QC sample reported by 18 laboratories were
      analyzed, and the MU of 1 laboratory was estimated by the statistical model
      described. CONCLUSION: Using peer-group run control data, MU of serologic testing
      can be estimated by taking into account both imprecision and bias.

PMID- 16410343
TI  - The aggregation of alpha-synuclein is stimulated by FK506 binding proteins as
      shown by fluorescence correlation spectroscopy.
AB  - Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's
      disease (PD). We have used fluorescence correlation spectroscopy (FCS) to study
      alpha-SYN aggregation in vitro and discovered that this process is clearly
      accelerated by addition of FK506 binding proteins (FKBPs). This effect was
      observed both with E. coli SlyD FKBP and with human FKBP12 and was counteracted
      by FK506, a specific inhibitor of FKBP. The alpha-SYN aggregates formed in the
      presence of FKBP12 showed fibrillar morphology. The rotamase activity of FKBP
      apparently accelerates the folding and subsequent aggregation of alpha-SYN. Since
      FK506 and other non-immunosuppressive FKBP inhibitors are known to display
      neuroregenerative and neuroprotective properties in disease models, the observed
      inhibition of rotamase activity and alpha-SYN aggregation, may explain their mode
      of action. Our results open perspectives for the treatment of PD with
      immunophilin ligands that inhibit a specific member of the FKBP family.

PMID- 16410344
TI  - Proteasome blockade exerts an antifibrotic activity by coordinately down
      regulating type I collagen and tissue inhibitor of metalloproteinase-1 and up
      regulating metalloproteinase-1 production in human dermal fibroblasts.
AB  - Tissue fibrosis results when dysregulation of extracellular matrix (ECM) turnover
      favors deposition of collagen and other ECM proteins over degradation. Fibrosis
      may then lead to organ dysfunction and pathology as observed in systemic
      sclerosis (SSc). In the present study, we investigated the antifibrotic
      properties of proteasome blockade. A dose- and time-dependent reduction in type-I
      collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) production was
      observed in normal fibroblasts exposed to proteasome inhibitors (PI). In the same
      culture conditions, metalloproteinase-1 (MMP-1) protein and the collagenolytic
      activity on type I collagen was increased. The steady-state mRNA levels of
      COL1A1, TIMP-1, and MMP-1 paralleled protein levels. These effects were dominant
      over the profibrotic properties of TGF-beta and were observed with fibroblasts
      generated from normal and SSc skin. PI decreased type I collagen mRNA levels with
      kinetics similar to those observed with DRB, a specific RNA polymerase II
      inhibitor, thus indicating transcriptional inhibition. Of interest, PI induced c
      Jun phosphorylation and c-Jun nuclear accumulation. The specific N-terminal Jun
      kinase inhibitor SP-600125 selectively abrogated c-Jun phosphorylation and, in a
      dose-dependent fashion, the up-regulated synthesis of MMP-1 induced by PI.
      Finally, PI did not affect fibroblast viability. Thus, the coordinated down
      regulation of collagen and TIMP-1 and up-regulation of MMP-1 renders proteasome
      blockade an attractive strategy for treating conditions as SSc, characterized by
      excessive fibrosis.

PMID- 16410345
TI  - Flagellin of Pseudomonas aeruginosa inhibits Na+ transport in airway epithelia.
AB  - Pseudomonas aeruginosa causes severe life-threatening airway infections that are
      a frequent cause for hospitalization of cystic fibrosis (CF) patients. These Gram
      negative pathogens possess flagella that contain the protein flagellin as a major
      structural component. Flagellin binds to the host cell glycolipid asialoGM1
      (ASGM1), which appears enriched in luminal membranes of respiratory epithelial
      cells. We demonstrate that in mouse airways, luminal exposure to flagellin leads
      to inhibition of Na+ absorption by the epithelial Na+ channel ENaC, but does not
      directly induce a secretory response. Inhibition of ENaC was observed in tracheas
      of wild-type mice and was attenuated in mice homozygous for the frequent cystic
      fibrosis conductance regulator (CFTR) mutation G551D. Similar to flagellin, anti
      ASGM1 antibody also inhibited ENaC. The inhibitory effects of flagellin on ENaC
      were attenuated by blockers of the purinergic signaling pathway, although an
      increase in the intracellular Ca2+ concentration by recombinant or purified
      flagellin or whole flagella was not observed. Because an inhibitor of the mitogen
      activated protein kinase (MAPK) pathway also attenuated the effects of flagellin
      on Na+ absorption, we conclude that flagellin exclusively inhibits ENaC, probably
      due to release of ATP and activation of purinergic receptors of the P2Y subtype.
      Stimulation of these receptors activates the MAPK pathway, thereby leading to
      inhibition of ENaC. Thus, P. aeruginosa reduces Na+ absorption, which could
      enhance local mucociliary clearance, a mechanism that seem to be attenuated in
      CF.

PMID- 16410346
TI  - The inconsistency of "optimal" cutpoints obtained using two criteria based on the
      receiver operating characteristic curve.
AB  - The use of biomarkers is of ever-increasing importance in clinical diagnosis of
      disease. In practice, a cutpoint is required for dichotomizing naturally
      continuous biomarker levels to distinguish persons at risk of disease from those
      who are not. Two methods commonly used for establishing the "optimal" cutpoint
      are the point on the receiver operating characteristic curve closest to (0,1) and
      the Youden index, J. Both have sound intuitive interpretations--the point closest
      to perfect differentiation and the point farthest from none, respectively--and
      are generalizable to weighted sensitivity and specificity. Under the same
      weighting of sensitivity and specificity, these two methods identify the same
      cutpoint as "optimal" in certain situations but different cutpoints in others. In
      this paper, the authors examine situations in which the two criteria agree or
      disagree and show that J is the only "optimal" cutpoint for given weighting with
      respect to overall misclassification rates. A data-driven example is used to
      clarify and demonstrate the magnitude of the differences. The authors also
      demonstrate a slight alteration in the (0,1) criterion that retains its intuitive
      meaning while resulting in consistent agreement with J. In conclusion, the
      authors urge that great care be taken when establishing a biomarker cutpoint for
      clinical use.

PMID- 16410347
TI  - Limits to causal inference based on Mendelian randomization: a comparison with
      randomized controlled trials.
AB  - "Mendelian randomization" refers to the random assortment of genes transferred
      from parent to offspring at the time of gamete formation. This process has been
      compared to a randomized controlled trial of genetic variants. This could greatly
      aid observational epidemiology by potentially allowing an unbiased estimate of
      the effects of gene products on disease outcomes. However, studies utilizing
      Mendelian randomization to estimate effects of gene products on outcomes should
      be interpreted with caution. In this paper, the authors discuss some of the
      challenges facing epidemiologists in the analysis and interpretation of Mendelian
      randomization studies, particularly those that become apparent when the analogy
      with randomized controlled trials is closely examined. The authors conclude that
      Mendelian randomization is a powerful addition to etiologic research tools.
      However, care must be taken, because drawing valid causal inferences from its
      application depends upon more extensive assumptions than are required in
      randomized controlled trials.

PMID- 16410348
TI  - The effect of social engagement on incident dementia: the Honolulu-Asia Aging
      Study.
AB  - The authors examined whether low levels of social engagement in midlife and late
      life were associated with the risk of incident dementia in 2,513 Japanese
      American men who have been followed since 1965 as part of the Honolulu Heart
      Program and the Honolulu-Asia Aging Study. In 1991, assessment of dementia began;
      incident dementia cases (n = 222) were diagnosed in 1994 and 1997. Social
      engagement was assessed in midlife (1968) and late life (1991). The relation
      between social engagement and dementia risk was examined using Cox proportional
      hazards models. No level of midlife social engagement was associated with the
      risk of dementia. In late life, compared with participants in the highest
      quartile of late-life social engagement, those in the lowest quartile had a
      significantly increased risk of dementia (hazard ratio = 2.34, 95% confidence
      interval: 1.18, 4.65). However, compared with those who were in the highest
      quartile of social engagement at both midlife and late life, only decreased
      social engagement from midlife to late life was associated with an increased risk
      of dementia (hazard ratio = 1.87, 95% confidence interval: 1.12, 3.13). Although
      low social engagement in late life is associated with risk of dementia, levels of
      late-life social engagement may already have been modified by the dementing
      process and may be associated with prodromal dementia.

PMID- 16410349
TI  - Agreement between responses to a standardized asthma questionnaire and a
      questionnaire following a demonstration of asthma symptoms in adults.
AB  - Asthma epidemiology relies heavily on standardized questionnaires, but little is
      known about the understanding of asthma symptoms among adults in the community.
      In 2004, the authors assessed the level of agreement between responses to a
      standardized questionnaire and responses to a questionnaire completed by
      participants after viewing a demonstration of asthma symptoms. The study involved
      601 young adults from Chile. The field-workers were trained to explain and
      demonstrate the asthma symptoms to the participants. The symptoms were wheeze,
      waking at night with breathlessness, breathlessness following exercise, and
      waking with cough. The kappa statistic did not exceed 0.4, and the recorded
      prevalence of asthma symptoms following the demonstration was 30-60% lower than
      that for the standardized questionnaire. Using bronchial responsiveness as the
      proxy gold standard, the positive likelihood ratios for wheeze and waking short
      of breath were higher following symptom demonstration. The low agreement between
      the standardized questionnaire and the postdemonstration questionnaire and the
      likelihood ratios' closeness to 1 for the standardized questionnaire decreases
      the authors' confidence in the appropriateness of this tool for estimating the
      prevalence of asthma in the community. For etiologic studies of asthma, it may
      contribute to the lack of consistency between different studies analyzing the
      same etiologic exposures.

PMID- 16410350
TI  - The relation between visceral fat measurement and torso level--is one level
      better than another? The Atherosclerosis Risk in Communities Study, 1990-1992.
AB  - Intraabdominal fat (IAF) area is often measured indirectly in epidemiologic
      studies. The authors recruited 147 participants from the second examination (1990
      1992) of the Atherosclerosis Risk in Communities Study to examine IAF area and
      determine whether there were differences in IAF area and distribution by
      location. Magnetic resonance imaging was used to image four 10-mm slices between
      the second and fourth lumbar vertebrae by an inverse recovery method, and IAF was
      calculated from each image. The authors constructed gender-specific mixed models
      with IAF area as the outcome and the location of imaging along the torso as the
      independent variable, using random intercepts to account for between-person
      variation in IAF area. The torso location of IAF measurement was a significant
      predictor of IAF area in both men (p = 0.02) and women (p < 0.0001) after
      adjustment for body mass index. A significant positive interaction between age
      and location was seen in men, with increasing IAF area moving down the torso with
      older ages. Using magnetic resonance imaging, location along the torso yields
      different IAF areas and distributions independently of body mass index in both
      genders, with measurement at the second lumbar vertebra (slightly above the
      umbilicus) capturing the largest amount of IAF. Studies that attempt to link IAF
      with cardiovascular disease risk factors should consider measurement location to
      accurately capture the association.

PMID- 16410351
TI  - Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated
      gene-disease associations.
AB  - The authors evaluated whether statistically significant violations of Hardy
      Weinberg equilibrium (HWE) or the magnitude of deviations from HWE may contribute
      to the problem of replicating postulated gene-disease associations across
      different studies. Forty-two gene-disease associations assessed in meta-analyses
      of 591 studies were examined. Studies with disease-free controls in which HWE was
      violated gave significantly different results from HWE-conforming studies in five
      instances. Exclusion of the former studies resulted in loss of statistical
      significance of the overall meta-analysis in three instances and more than a 10%
      change in the summary odds ratio in six. Exclusion of HWE-violating studies
      changed the formal significance of the estimated between-study heterogeneity in
      three instances. After adjustment for the magnitude of the deviation from HWE for
      the controls, formal significance was lost in another three instances. Studies
      adjusted for the magnitude of deviation from HWE tended to become more
      heterogeneous among themselves, and, for seven gene-disease associations, between
      study heterogeneity became significant, while it was not so in the unadjusted
      analyses. Gene-disease association studies and meta-analyses thereof should
      routinely scrutinize the potential impact of HWE violations as well as
      nonsignificant deviations from the exact frequencies expected under HWE.
      Postulated genetic associations with modest-sized odds ratios and borderline
      statistical significance may not be robust in such sensitivity analyses.

PMID- 16410352
TI  - Protection conferred by recombinant Yersinia pestis antigens produced by a rapid
      and highly scalable plant expression system.
AB  - Plague is still an endemic disease in different regions of the world. Increasing
      reports of incidence, the discovery of antibiotic resistance strains, and concern
      about a potential use of the causative bacteria Yersinia pestis as an agent of
      biological warfare have highlighted the need for a safe, efficacious, and rapidly
      producible vaccine. The use of F1 and V antigens and the derived protein fusion
      F1-V has shown great potential as a protective vaccine in animal studies. Plants
      have been extensively studied for the production of pharmaceutical proteins as an
      inexpensive and scalable alternative to common expression systems. In the current
      study the recombinant plague antigens F1, V, and fusion protein F1-V were
      produced by transient expression in Nicotiana benthamiana by using a
      deconstructed tobacco mosaic virus-based system that allowed very rapid and
      extremely high levels of expression. All of the plant-derived purified antigens,
      administered s.c. to guinea pigs, generated systemic immune responses and
      provided protection against an aerosol challenge of virulent Y. pestis.

PMID- 16410354
TI  - A gain-control theory of binocular combination.
AB  - In binocular combination, light images on the two retinas are combined to form a
      single "cyclopean" perceptual image, in contrast to binocular rivalry which
      occurs when the two eyes have incompatible ("rivalrous") inputs and only one
      eye;s stimulus is perceived. We propose a computational theory for binocular
      combination with two basic principles of interaction: in every spatial
      neighborhood, each eye (i) exerts gain control on the other eye's signal in
      proportion to the contrast energy of its own input and (ii) additionally exerts
      gain control on the other eye's gain control. For stimuli of ordinary contrast,
      when either eye is stimulated alone, the predicted cyclopean image is the same as
      when both eyes are stimulated equally, coinciding with an easily observed
      property of natural vision. The gain-control theory is contrast dependent: Very
      low-contrast stimuli to the left- and right-eye add linearly to form the
      predicted cyclopean image. The intrinsic nonlinearity manifests itself only as
      contrast increases. To test the theory more precisely, a horizontal sine wave
      grating of 0.68 cycles per degree is presented to each eye. The gratings differ
      in contrast and phase. The predicted (and perceived) cyclopean grating also is a
      sine wave; its apparent phase indicates the relative contribution of the two eyes
      to the cyclopean image. For 48 measured combinations of phase and contrast, the
      theory with only one estimated parameter accounts for 95% of the variance of the
      data. Therefore, a simple, robust, physiologically plausible gain-control theory
      accurately describes an early stage of binocular combination.

PMID- 16410353
TI  - Molecular basis for substrate recognition by MTMR2, a myotubularin family
      phosphoinositide phosphatase.
AB  - Myotubularins, a large family of catalytically active and inactive proteins,
      belong to a unique subgroup of protein tyrosine phosphatases that use inositol
      phospholipids, rather than phosphoproteins, as physiological substrates. Here, by
      integrating crystallographic and deuterium-exchange mass spectrometry studies of
      human myotubularin-related protein-2 (MTMR2) in complex with phosphoinositides,
      we define the molecular basis for this unique substrate specificity.
      Phosphoinositide substrates bind in a pocket located on a positively charged face
      of the protein, suggesting an electrostatic mechanism for membrane targeting. A
      flexible, hydrophobic helix makes extensive interactions with the diacylglycerol
      moieties of substrates, explaining the specificity for membrane-bound
      phosphoinositides. An extensive H-bonding network and charge-charge interactions
      within the active site pocket determine phosphoinositide headgroup specificity.
      The conservation of these specificity determinants within the active, but not the
      inactive, myotubularins provides insight into the functional differences between
      the active and inactive members.

PMID- 16410355
TI  - Two peptide sequences can function cooperatively to facilitate binding and
      unfolding by ClpA and degradation by ClpAP.
AB  - Clp/Hsp100 proteins comprise a large family of AAA(+) ATPases. Some Clp proteins
      function alone as molecular chaperones, whereas others act in conjunction with
      peptidases, forming ATP-dependent proteasome-like compartmentalized proteases.
      Protein degradation by Clp proteases is regulated primarily by substrate
      recognition by the Clp ATPase component. The ClpA and ClpX ATPases of Escherichia
      coli generally recognize short amino acid sequences that are located near the N
      or C terminus of a substrate. However, both ClpAP and ClpXP are able to degrade
      proteins in which the end containing the recognition signal is fused to GFP such
      that the signal is in the interior of the primary sequence of the substrate.
      Here, we tested whether the internal ClpA recognition signal was the sole element
      required for targeting the substrate to ClpA. The results show that, in the
      absence of a high-affinity peptide recognition signal at the terminus, two
      elements are important for recognition of GFP-RepA fusion proteins by ClpA. One
      element is the natural ClpA recognition signal located at the junction of GFP and
      RepA in the fusion protein. The second element is the C-terminal peptide of the
      fusion protein. Together, these two elements facilitate binding and unfolding by
      ClpA and degradation by ClpAP. The internal site appears to function similarly to
      Clp adaptor proteins but, in this case, is covalently attached to the polypeptide
      containing the terminal tag and both the "adaptor" and "substrate" modules are
      degraded.

PMID- 16410356
TI  - Direct neurophysiological evidence for spatial suppression surrounding the focus
      of attention in vision.
AB  - The spatial focus of attention has traditionally been envisioned as a simple
      spatial gradient of enhanced activity that falls off monotonically with
      increasing distance. Here, we show with high-density magnetoencephalographic
      recordings in human observers that the focus of attention is not a simple
      monotonic gradient but instead contains an excitatory peak surrounded by a narrow
      inhibitory region. To demonstrate this center-surround profile, we asked subjects
      to focus attention onto a color pop-out target and then presented probe stimuli
      at various distances from the target. We observed that the electromagnetic
      response to the probe was enhanced when the probe was presented at the location
      of the target, but the probe response was suppressed in a narrow zone surrounding
      the target and then recovered at more distant locations. Withdrawing attention
      from the pop-out target by engaging observers in a demanding foveal task
      eliminated this pattern, confirming a truly attention-driven effect. These
      results indicate that neural enhancement and suppression coexist in a spatially
      structured manner that is optimal to attenuate the most deleterious noise during
      visual object identification.

PMID- 16410357
TI  - Polyphosphate modulates blood coagulation and fibrinolysis.
AB  - Inorganic polyphosphate is an abundant component of acidocalcisomes of bacteria
      and unicellular eukaryotes. Human platelet dense granules strongly resemble
      acidocalcisomes, and we recently showed that they contain substantial amounts of
      polyphosphate, which is secreted upon platelet activation. We now report that
      polyphosphate is a potent hemostatic regulator, accelerating blood clotting by
      activating the contact pathway and promoting the activation of factor V, which in
      turn results in abrogation of the function of the natural anticoagulant protein,
      tissue factor pathway inhibitor. Polyphosphate was also found to delay clot lysis
      by enhancing a natural antifibrinolytic agent, thrombin-activatable fibrinolysis
      inhibitor. Polyphosphate is unstable in blood or plasma, owing to the presence of
      phosphatases. We propose that polyphosphate released from platelets or
      microorganisms initially promotes clot formation and stability; subsequent
      degradation of polyphosphate by blood phosphatases fosters inhibition of clotting
      and activation of fibrinolysis during wound healing.

PMID- 16410358
TI  - Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia
      in diabetic mice.
AB  - Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and
      cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose
      metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic
      overexpression of constitutively active FXR by adenovirus-mediated gene transfer
      significantly lowered blood glucose levels in both diabetic db/db and wild-type
      mice. Consistent with these data, FXR null mice exhibited glucose intolerance and
      insulin insensitivity. We further demonstrate that activation of FXR in db/db
      mice repressed hepatic gluconeogenic genes and increased hepatic glycogen
      synthesis and glycogen content by a mechanism that involves enhanced insulin
      sensitivity. In view of its central roles in coordinating regulation of both
      glucose and lipid metabolism, we propose that FXR agonists are promising
      therapeutic agents for treatment of diabetes mellitus.

PMID- 16410360
TI  - Unexpected NO-dependent DNA binding by the CooA homolog from Carboxydothermus
      hydrogenoformans.
AB  - CooA, the CO-sensing heme protein from Rhodospirillum rubrum, regulates the
      expression of genes that encode a CO-oxidation system, allowing R. rubrum to use
      CO as a sole energy source. To better understand the gas-sensing regulation
      mechanism used by R. rubrum CooA and its homologs in other organisms, we
      characterized spectroscopically and functionally the Fe(II), Fe(II)-NO, and
      Fe(II)-CO forms of CooA from Carboxydothermus hydrogenoformans. Surprisingly, and
      unlike R. rubrum CooA, C. hydrogenoformans CooA binds NO to form a six-coordinate
      Fe(II)-NO heme that is active for DNA binding in vitro and in vivo. In contrast,
      R. rubrum CooA, which is exquisitely specific for CO, forms a five-coordinate
      Fe(II)-NO adduct that is inactive for DNA binding. Based on analyses of protein
      variants and temperature studies, NO-dependent DNA binding by C. hydrogenoformans
      CooA is proposed to result from a greater apparent stability of the six
      coordinate Fe(II)-NO adduct at room temperature. Results from the present study
      strengthen the proposal that CO specificity in the CooA activation mechanism is
      based on the requirement for a small, neutral distal ligand, which in turn
      affects the relative positioning of the ligand-bound heme.

PMID- 16410359
TI  - Dual signaling is differentially activated by different active states of the
      metabotropic glutamate receptor 1alpha.
AB  - The metabotropic glutamate receptor 1alpha (mGluR1alpha) is crucial for some
      forms of synaptic plasticity, by inducing various cell responses via coupling to
      various types of G proteins. Upon glutamate binding, an active conformation,
      closed-open/active, of the extracellular domain is stabilized, which induces
      dimeric rearrangement in the intracellular domains, resulting in the initiation
      of downstream signals. We have confirmed that mGluR1alpha functionally interacts
      with both Gq and Gs pathways; a combination of fluorescent indicators showed that
      glutamate increased intracellular Ca(2+) and cAMP concentration ([Ca(2+)](i) and
      [cAMP](i)). By contrast, Gd(3+), a different type of ligand whose recognition
      site on mGluR1alpha is distinct from the glutamate site, increased only
      [Ca(2+)](i) and the concentration-activation curve was bell-shaped. FRET analysis
      revealed that a low concentration of Gd(3+) induced dimeric rearrangement of the
      intracellular domains of mGluR1alpha as does glutamate, whereas a high
      concentration of Gd(3+) reversed the FRET efficiency, which was consistent with a
      bell-shaped relationship between concentration and Gq activation. These results
      suggest that Gd(3+) induces an active and a sort of "inactivated" conformation in
      mGluR1alpha. The Gd(3+)-induced active state is considered to correspond to the
      closed-closed/active conformation, revealed by previous x-ray crystallographic
      studies. In conclusion, the glutamate-induced closed-open/active state coupled
      both to Gs and Gq proteins whereas the Gd(3+)-induced closed-closed/active
      conformation state preferred Gq to Gs, suggesting that mGluR1alpha serves not
      only as a simple on/off switch but also as a multiple signaling path regulator.

PMID- 16410361
TI  - Antiviral prophylaxis in patients with haematological malignancies and solid
      tumours: Guidelines of the Infectious Diseases Working Party (AGIHO) of the
      German Society for Hematology and Oncology (DGHO).
AB  - Morbidity and mortality in patients with malignancies are increased by viral
      infections. These mostly are reactivations of asymptomatic latent infections.
      They primarily concern clinical entities associated with the reactivation of
      herpes viruses, such as varicella zoster virus (VZV) and cytomegalovirus (CMV).
      Respiratory tract infections caused by influenza, parainfluenza or respiratory
      syncytial virus (RSV) are less common. Since reactivation of latent infections
      has major clinical impact, antiviral prophylaxis is an attractive approach for
      patients expecting immunosuppression. The main risk factor for clinically
      relevant reactivation is profound disruption of cellular immune response.
      Duration and severity of chemotherapy induced neutropenia are of lesser
      importance. The risk of viral complications rises significantly in the presence
      of sustained suppression of T-cell function, e.g. in recipients of allogeneic
      stem cell transplants or of alemtuzumab (Campath-1H) antibody therapy. The
      objective of this guideline is to review the basis of prophylactic strategies and
      to provide recommendations for clinicians treating patients with haematological
      malignancies and solid tumors.

PMID- 16410362
TI  - Life-threatening toxic epidermal necrolysis during voriconazole therapy for
      invasive aspergillosis after chemotherapy.

PMID- 16410363
TI  - A phase II study on metastatic breast cancer patients treated with weekly
      vinorelbine with or without trastuzumab according to HER2 expression: changing
      the natural history of HER2-positive disease.
AB  - PURPOSE: To observe whether in pretreated metastatic breast cancer patients with
      HER2-positive disease vinorelbine plus trastuzumab can produce different overall
      response rate (ORR), time to progression (TTP), and overall survival (OS) from
      women with HER2-negative tumors treated with vinorelbine alone. METHODS: Between
      June 2000 and January 2004, 68 consecutive women were enrolled: 33 patients
      received vinorelbine (V) alone, while 35 patients were given trastuzumab plus
      vinorelbine (T+V) according to HER2 expression determined by
      immunohistochemistry. In tumors scored +2, HER2 gene amplification was determined
      by fluorescence in situ hybridization. RESULTS: In patients treated with V (HER2
      negative tumors) the ORR was 27.3%, while in those given T+V (HER2 positive
      tumors) the ORR was 51.4%. The median duration of response was 8 months for women
      treated with V and 10 months for those who received T+V. Patients given T+V had a
      longer TTP (9 months) and OS (27 months) than those receiving V alone (6 months
      and 22 months respectively). Toxicity was mild in both groups. Concerning
      cardiotoxicity in T+V group, 7 patients (20%) had left ventricular systolic
      disfunction. CONCLUSION: Our data suggest that trastuzumab can change the natural
      history of HER2-positive metastatic breast cancer. In fact, when treated with
      trastuzumab, women with HER2-positive disease had better prognosis than patients
      with HER2-negative tumors. Conducting a formal phase III trial comparing
      vinorelbine alone vs vinorelbine plus trastuzumab in HER2-positive metastatic
      breast cancer women could be debatable.

PMID- 16410365
TI  - Quantifying esophageal peristalsis with high-resolution manometry: a study of 75
      asymptomatic volunteers.
AB  - The vastly enhanced spatial resolution of high-resolution manometry (HRM) makes
      it possible to simultaneous monitor contractile activity over the entire length
      of the esophagus. The aim of this investigation was to define the essential
      features of esophageal peristalsis in novel HRM paradigms and establish their
      normative values. Ten 5-ml water swallows were recorded in each of 75
      asymptomatic controls with a solid-state manometric assembly incorporating 36
      circumferential sensors spaced at 1-cm intervals positioned to record from the
      hypopharynx to the stomach. The data set was then subjected to intensive
      computational analysis to distill out the essential characteristics of normal
      peristalsis. Esophageal peristalsis was conceptualized in terms of a proximal
      contraction, a distal contraction, and a transition zone separating the two. Each
      contractile segment was quantified in length and then normalized among subjects
      to summarize focal fluctuation of contractile amplitude and propagation velocity.
      Furthermore, the temporal and spatial characteristics of the transition zone
      separating the proximal and distal contraction were quantified. For each
      paradigm, graphics were developed, establishing median values along with the 5th
      to 95th percentile range of observed variation. In addition, the synchronization
      between peristalsis and esophagogastric junction relaxation was analyzed using a
      novel concept of the outflow permissive pressure gradient. We performed a
      detailed analysis of esophageal peristalsis aimed at quantifying its essential
      features and, in so doing, devised new paradigms for the quantification of
      peristaltic function that will hopefully optimize the utility of HRM in clinical
      and investigative studies.

PMID- 16410364
TI  - Adiponectin normalizes LPS-stimulated TNF-alpha production by rat Kupffer cells
      after chronic ethanol feeding.
AB  - Chronic ethanol feeding sensitizes Kupffer cells to activation by
      lipopolysaccharide (LPS), leading to increased production of tumor necrosis
      factor-alpha (TNF-alpha). Adiponectin treatment protects mice from ethanol
      induced liver injury. Because adiponectin has anti-inflammatory effects on
      macrophages, we hypothesized that adiponectin would normalize chronic ethanol
      induced sensitization of Kupffer cells to LPS-mediated signals. Serum adiponectin
      concentrations were decreased by 45% in rats fed an ethanol-containing diet for 4
      wk compared with pair-fed rats. Adiponectin dose dependently inhibited LPS
      stimulated accumulation of TNF-alpha mRNA and peptide in Kupffer cells from both
      pair- and ethanol-fed rats. Kupffer cells from ethanol-fed rats were more
      sensitive to both globular (gAcrp) and full-length adiponectin (flAcrp) than
      Kupffer cells from pair-fed controls with suppression at 10 ng/ml adiponectin
      after chronic ethanol feeding. Kupffer cells expressed both adiponectin receptors
      1 and 2; chronic ethanol feeding did not change the expression of adiponectin
      receptor mRNA or protein. gAcrp suppressed LPS-stimulated ERK1/2 and p38
      phosphorylation as well as IkappaB degradation at 100-1,000 ng/ml in Kupffer
      cells from both pair- and ethanol-fed rats. However, only LPS-stimulated ERK1/2
      phosphorylation was sensitive to 10 ng/ml gAcrp. gAcrp also normalized LPS
      stimulated DNA binding activity of early growth response-1 with greater
      sensitivity in Kupffer cells from rats fed chronic ethanol. In conclusion, these
      results demonstrate that Kupffer cells from ethanol-fed rats are more sensitive
      to the anti-inflammatory effects of both gAcrp and flAcrp. Suppression of LPS
      stimulated ERK1/2 signaling by low concentrations of gAcrp was associated with
      normalization of TNF-alpha production by Kupffer cells after chronic ethanol
      exposure.

PMID- 16410366
TI  - Proteomic analysis of iron overload in human hepatoma cells.
AB  - Iron-mediated organ damage is common in patients with iron overload diseases,
      namely, hereditary hemochromatosis. Massive iron deposition in parenchymal
      organs, particularly in the liver, causes organ dysfunction, fibrosis, cirrhosis,
      and also hepatocellular carcinoma. To obtain deeper insight into the poorly
      understood and complex cellular response to iron overload and consequent
      oxidative stress, we studied iron overload in liver-derived HepG2 cells. Human
      hepatoma HepG2 cells were exposed to a high concentration of iron for 3 days, and
      protein expression changes initiated by the iron overload were studied by two
      dimensional electrophoresis and mass spectrometry. From a total of 1,060 spots
      observed, 21 spots were differentially expressed by iron overload. We identified
      19 of them; 11 identified proteins were upregulated, whereas 8 identified
      proteins showed a decline in response to iron overload. The differentially
      expressed proteins are involved in iron storage, stress response and protection
      against oxidative stress, protein folding, energy metabolism, gene expression,
      cell cycle regulation, and other processes. Many of these molecules have not been
      previously suggested to be involved in the response to iron overload and the
      consequent oxidative stress.

PMID- 16410367
TI  - The transcription factor interferon regulatory factor-1 mediates liver damage
      during ischemia-reperfusion injury.
AB  - Hepatic ischemia occurs in the settings of trauma, transplantation, and elective
      liver resections. The initiating events that account for local organ damage are
      only partially understood. Interferon (IFN) regulatory factor-1 (IRF-1) is a
      transcription factor that regulates the expression of a number of genes involved
      in both innate and acquired immunity; however, its function in liver injury is
      unknown. Therefore, the purpose of this study was to investigate the role of IRF
      1 in hepatic ischemia-reperfusion (I/R) injury. In C57BL/6 mice undergoing 60 min
      of hepatic ischemia, IRF-1 protein expression increased as early as 1 h after
      reperfusion. IRF-1 knockout mice were significantly protected from hepatic I/R
      induced damage compared with their wild-type controls. Hepatic I/R injury
      resulted in marked activation of the MAP kinase c-Jun NH(2)-terminal kinase (JNK)
      in wild-type mice but not IRF-1 knockout mice. IRF-1 knockout mice also exhibited
      significantly lower hepatic expression of TNF-alpha, IL-6, ICAM-1, and inducible
      nitric oxide synthase (iNOS) mRNA. Adenoviral delivery of IRF-1 into C57BL/6 mice
      resulted in increased liver damage even without an ischemic insult. This injury
      was associated with increased JNK activation and hepatic iNOS expression. Because
      IRF-1 contributed to liver injury, we also examined for inflammatory signals that
      regulated IRF-1 gene expression in cultured hepatocytes. Whereas IFN-gamma and
      IFN-beta were strong inducers of IRF-1 mRNA (>10-fold) in a time- and dose
      dependent manner, TNF-alpha and IL-1beta also induced IRF-1 mRNA to a lesser
      extent (2- to 3-fold). IL-6 and lipopolysaccharide had no effect on IRF-1
      expression. This study demonstrates that IRF-1 exerts a harmful role in hepatic
      I/R injury by modulating the expression of multiple inflammatory mediators. We
      further show that IRF-1-mediated injury involves the activation of JNK and that
      hepatocellular IRF-1 expression itself is regulated by specific cytokines.

PMID- 16410368
TI  - Intestinal function of gene-targeted mice lacking serum- and glucocorticoid
      inducible kinase 1.
AB  - In vitro experiments have revealed the ability of serum- and glucocorticoid
      inducible kinase 1 (SGK1) to stimulate intestinal Na(+)-coupled glucose
      cotransporter 1 (SGLT1) and intestinal Na(+)/H(+) exchanger 3 (NHE3). The present
      study explored the contribution of SGK1 to the regulation of intestinal transport
      in vivo. SGK1 transcript levels were determined by real-time PCR and glucose
      induced currents (I(g)) reflecting SGLT1 activity by Ussing chamber experiments.
      BCECF fluorescence was utilized for the determination of Na(+)-dependent pH
      recovery from an ammonium pulse (DeltapH(NHE)) reflecting NHE activity. As a
      result, intestinal SGK1 transcript levels were significantly enhanced by a 4-day
      treatment with 10 microg.mg body wt(-1).day(-1) dexamethasone (Dex). I(g) was,
      under control conditions, virtually identical in sgk1 knockout mice (sgk1(-/-))
      and their wild type littermates (sgk1(+/+)). A 4-day treatment with Dex, however,
      increased I(g) approximately threefold in sgk1(+/+) mice but not in sgk1(-/-)
      mice. DeltapH(NHE) was similar in sgk1(-/-) and sgk1(+/+) mice before treatment.
      Dex increased DeltapH(NHE) approximately threefold in sgk1(+/+) mice and
      approximately twofold in sgk1(-/-)mice, an effect significantly blunted in the
      presence of the specific NHE3 blocker S-3226 (10 microM). According to Western
      blot analysis, Dex significantly enhanced SGLT1 and NHE3 protein abundance in
      brush-border membranes of sgk1(+/+) mice but not of sgk1(-/-)mice. In conclusion,
      basic functions of SGLT1 and NHE3 in the intestine do not require stimulation by
      SGK1. However, the effects of glucocorticoids on SGLT1 are fully, and on NHE3
      partially, dependent on SGK1.

PMID- 16410369
TI  - Outcomes of patients in clinical trials with ST-segment elevation myocardial
      infarction among countries with different gross national incomes.
AB  - AIMS: To evaluate whether there is an association between 30-day mortality in
      patients with ST-segment elevation myocardial infarction (STEMI) included in
      clinical trials and country gross national income (GNI). METHODS AND RESULTS: A
      retrospective analysis of the databases of five randomized trials including 50
      310 patients with STEMI (COBALT 7169, GIK-2 2931, HERO-2 17,089, ASSENT-2 17,005,
      and ASSENT-3 6116 patients) from 53 countries was performed. Countries were
      divided into three groups according to their GNI based on the World Bank data:
      low (less than 2900 US dollars), medium (between 2900 US dollars and 9000 US
      dollars), and high GNI (more than 9000 US dollars per capita). Baseline
      characteristics, in-hospital management variables, and 30-day outcomes were
      evaluated. A previously defined logistic regression model was used to adjust for
      differences in baseline characteristics and to predict mortality. The observed
      mortality was higher than the predicted mortality in the low (12.1 vs. 11.8%) and
      in the medium income groups (9.4 vs. 7.9%), whereas it was lower in the high
      income group (4.9 vs. 5.6%). CONCLUSION: An inverse relationship between
      mortality and GNI was observed in STEMI clinical trials. Most of the variability
      in mortality can be explained by differences in baseline characteristics;
      however, after adjustment, lower income countries have higher mortality than the
      expected.

PMID- 16410370
TI  - Genetic alterations in cancer knowledge system: analysis of gene mutations in
      mouse and human liver and lung tumors.
AB  - Mutational incidence and spectra for genes examined in both human and mouse lung
      and liver tumors were analyzed using the National Institute of Environmental
      Health Sciences (NIEHS) Genetic Alterations in Cancer (GAC) knowledge system. GAC
      is a publicly available, web-based system for evaluating data obtained from peer
      reviewed studies of genetic changes in tumors associated with exposure to
      chemical, physical, or biological agents, as well as spontaneous tumors. In mice,
      mutations in Kras2 and Hras-1 were the most common events reported for lung and
      liver tumors, respectively, whether chemically induced or spontaneous. There was
      a significant difference in Kras2 mutation incidence for spontaneous versus
      induced mouse lung tumors and in Hras-1 mutation incidence and spectrum for
      spontaneous versus induced mouse liver tumors. The major gene changes reported
      for human lung and liver tumors were in KRAS2 (lung only) and TP53. The KRAS2
      mutation incidence was similar for spontaneous and asbestos-induced human lung
      tumors, while the TP53 mutation incidence differed significantly. Aflatoxin B1,
      hepatitis B virus, hepatitis C virus, and vinyl chloride all caused TP53
      mutations in human liver tumors, but the mutation spectrum for each agent
      differed. The incidence of KRAS2 mutations in human compared to mouse lung tumors
      differed significantly, as did the incidence of Hras and p53 gene mutations in
      human compared to mouse liver tumors. Differences observed in the mutation
      spectra for agent-induced compared to spontaneous tumors and similarities in
      spectra for structurally similar agents support the concept that mutation spectra
      can serve as a "fingerprint" of exposure based on chemical structure.

PMID- 16410371
TI  - Inhibition of hepatobiliary transport as a predictive method for clinical
      hepatotoxicity of nefazodone.
AB  - Treatment with the antidepressant nefazodone has been associated with clinical
      idiosyncratic hepatotoxicty. Using membranes expressing human bile salt export
      pump (BSEP), human sandwich hepatocytes, and intact rats, we compared nefazodone
      and its marketed analogs, buspirone and trazodone. We found that nefazodone
      caused a strong inhibition of BSEP (IC(50) = 9 microM), inhibition of
      taurocholate efflux in human hepatocytes (IC(50) = 14 microM), and a transient
      increase in rat serum bile acids 1 h after oral drug administration. Buspirone or
      trazodone had no effect on biliary transport system. Nefazodone produced time-
      and concentration-dependent toxicity in human hepatocytes with IC(50) = 18 microM
      and 30 microM measured by inhibition of protein synthesis after 6 h and 24 h
      incubation, respectively. Toxicity was correlated with the amount of
      unmetabolized nefazodone. Partial recovery in toxicity by 24 h has been
      associated with metabolism of nefazodone to sulfate and glucuronide conjugates.
      The saturation of nefazodone metabolism resulted in sustained decrease in protein
      synthesis and cell death at 50 microM. The toxicity was not observed with
      buspirone or trazodone. Addition of 1-aminobenzotriazole (ABT), an inhibitor of
      CYP450, resulted in enhancement of nefazodone toxicity at 10 microM and was
      associated with accumulation of unmetabolized nefazodone. In human liver
      microsomes, ABT also prevented metabolism of nefazodone and formation of
      glutathione conjugates. We suggest that inhibition of bile acid transport by
      nefazodone is an indicator of potential hepatotoxicity. Our findings are
      consistent with the clinical experience and suggest that described methodology
      can be applied in the selection of nonhepatotoxic drug candidates.

PMID- 16410372
TI  - Comparison of early and late responses to antigen of sensitized guinea pig
      parenchymal lung strips.
AB  - The peripheral lung parenchyma has been studied as a component of the asthmatic
      inflammatory response. During induced constriction, tissue resistance increases
      in different asthma models. Approximately 60% of the asthmatic patients show
      early and late responses. The late response is characterized by more severe
      airway obstruction. In the present study, we evaluated lung parenchymal strips
      mechanics in ovalbumin-sensitized guinea pigs, trying to reproduce both early and
      late inflammatory responses. Oscillatory mechanics of lung strips were performed
      in a control group (C), in an early response group (ER), and in two late response
      groups: 17 h (L1) and 72 h (L2) after the last ovalbumin challenge. Measurements
      of resistance and elastance were obtained before and after ovalbumin challenge in
      C and ER groups and before and after acetylcholine challenge in all groups. Using
      morphometry, we assessed the density of eosinophils and smooth muscle cells, as
      well as collagen and elastin content in lung strips. The baseline and postagonist
      values of resistance and elastance were increased in ER, L1, and L2 groups
      compared with C (P < or = 0.001). The morphometric analysis showed an increase in
      alveolar eosinophil density in ER and L2 groups compared with C (P < 0.05). There
      was a significant correlation between eosinophil density in parenchymal strips of
      C, L1, and L2 groups and values of resistance and elastance postacetylcholine (r
      = 0.71, P = 0.001 and r = 0.74, P < 0.001, respectively). The results show that
      the lung parenchyma is involved in the late response, and the constriction
      response in this phase is related to the eosinophilic inflammation.

PMID- 16410374
TI  - Reports of the length dependence of fatigue are greatly exaggerated.
AB  - Relative force depression associated with muscle fatigue is reported to be
      greater when assessed at short vs. long muscle lengths. This appears to be due to
      a rightward shift in the force-length relationship. This rightward shift may be
      caused by stretch of in-series structures, making sarcomere lengths shorter at
      any given muscle length. Submaximal force-length relationships (twitch, double
      pulse, 50 Hz) were evaluated before and after repetitive contractions (50 Hz, 300
      ms, 1/s) in an in situ preparation of the rat medial gastrocnemius muscle. In
      some experiments, fascicle lengths were measured with sonomicrometry. Before
      repetitive stimulation, fascicle lengths were 11.3 +/- 0.8, 12.8 +/- 0.9, and
      14.4 +/- 1.2 mm at lengths corresponding to -3.6, 0, and 3.6 mm where 0 is a
      reference length that corresponds with maximal active force for double-pulse
      stimulation. After repetitive stimulation, there was no change in fascicle
      lengths; these lengths were 11.4 +/- 0.8, 12.6 +/- 0.9, and 14.2 +/- 1.2 mm. The
      length dependence of fatigue was, therefore, not due to a stretch of in-series
      structures. Interestingly, the rightward shift that was evident when active force
      was calculated in the traditional way (subtraction of the passive force measured
      before contraction) was not seen when active force was calculated by subtracting
      the passive force that was associated with the fascicle length reached at the
      peak of the contraction. This calculation is based on the assumption that passive
      force decreases as the fascicles shorten during a fixed-end contraction. This
      alternative calculation revealed similar postfatigue absolute active force
      depression at all lengths. In relative terms, a length dependence of fatigue was
      still evident, but this was greatly diminished compared with that observed when
      active force was calculated with the traditional method.

PMID- 16410373
TI  - Differential effects of strength training leading to failure versus not to
      failure on hormonal responses, strength, and muscle power gains.
AB  - The purpose of this study was to examine the efficacy of 11 wk of resistance
      training to failure vs. nonfailure, followed by an identical 5-wk peaking period
      of maximal strength and power training for both groups as well as to examine the
      underlying physiological changes in basal circulating anabolic and catabolic
      hormones. Forty-two physically active men were matched and then randomly assigned
      to either a training to failure (RF; n = 14), nonfailure (NRF; n = 15), or
      control groups (C; n = 13). Muscular and power testing and blood draws to
      determine basal hormonal concentrations were conducted before the initiation of
      training (T0), after 6 wk of training (T1), after 11 wk of training (T2), and
      after 16 wk of training (T3). Both RF and NRF resulted in similar gains in 1
      repetition maximum bench press (23 and 23%) and parallel squat (22 and 23%),
      muscle power output of the arm (27 and 28%) and leg extensor muscles (26 and
      29%), and maximal number of repetitions performed during parallel squat (66 and
      69%). RF group experienced larger gains in the maximal number of repetitions
      performed during the bench press. The peaking phase (T2 to T3) after NRF resulted
      in larger gains in muscle power output of the lower extremities, whereas after RF
      it resulted in larger gains in the maximal number of repetitions performed during
      the bench press. Strength training leading to RF resulted in reductions in
      resting concentrations of IGF-1 and elevations in IGFBP-3, whereas NRF resulted
      in reduced resting cortisol concentrations and an elevation in resting serum
      total testosterone concentration. This investigation demonstrated a potential
      beneficial stimulus of NRF for improving strength and power, especially during
      the subsequent peaking training period, whereas performing sets to failure
      resulted in greater gains in local muscular endurance. Elevation in IGFBP-3 after
      resistance training may have been compensatory to accommodate the reduction in
      IGF-1 to preserve IGF availability.

PMID- 16410375
TI  - Denervation effects on myonuclear domain size of rat diaphragm fibers.
AB  - Denervation (DNV) of rat diaphragm muscle (DIAm) leads to selective atrophy of
      type IIx and IIb fibers, whereas the cross-sectional area of type I and IIa
      fibers remains unchanged or slightly hypertrophied. DIAm DNV also increases
      satellite cell mitotic activity and myonuclear apoptosis. Similar to other
      skeletal muscles, DIAm fibers are multinucleated, and each myonucleus regulates
      the gene products in a finite fiber volume, i.e., myonuclear domain (MND). MND
      size varies across DIAm fiber types in rank order, I < IIa < IIx < IIb [fiber
      type based on myosin heavy chain isoform expression]. We hypothesized that, after
      DNV, the total number of myonuclei per fiber does not change and, accordingly,
      that MND changes proportionately to the change in fiber size regardless of fiber
      type. Adult rats underwent unilateral (right side) DIAm DNV, and after 2 wk
      single fibers were dissected. Fiber cross-sectional area, myonuclear number, and
      MND were measured by confocal microscopy, and these values in DNV DIAm were
      compared with those obtained in controls. After DNV, type I fibers hypertrophied,
      type IIa fiber size was unchanged, and type IIx and IIb fibers atrophied compared
      with control. The total number of myonuclei per fiber was not affected by DNV.
      Accordingly, after DNV, type I fiber MND increased by 25%, whereas it decreased
      in type IIx and IIb fibers by 50 and 70%, respectively. These results suggest
      that MND is not maintained after DNV-induced DIAm fiber hypertrophy or atrophy.
      These results are interpreted with respect to consequent effects of DNV on
      myonuclear transcriptional activity and protein turnover.

PMID- 16410376
TI  - Sex difference in cardiomyocyte function in normal and metallothionein transgenic
      mice: the effect of diabetes mellitus.
AB  - Evidence suggests a sex difference in intrinsic physiological and diabetic
      myocardial contractile function related to antioxidant properties of female
      ovarian hormones. This study was designed to examine the effect of cardiac
      overexpression of antioxidant metallothionein on intrinsic and diabetic
      cardiomyocyte function. Weight-matched wild-type (FVB) and metallothionein
      transgenic mice of both sexes were made diabetic with streptozotocin (220 mg/kg).
      Contractile and intracellular Ca2+ properties were evaluated including peak
      shortening (PS), time to PS, time to 90% relengthening (TR90), maximal velocity
      of shortening or relengthening (+/- dL/dt), fura-2 fluorescence intensity change,
      and Ca2+ decay rate. Akt and transcription factor c-Jun levels were evaluated by
      Western blot. Myocytes from female FVB mice exhibited lower PS, +/- dL/dt, and
      fura-2 fluorescence intensity change, prolonged time to PS, TR90, and Ca2+ decay
      compared with male FVB mice. Interestingly, this sex difference was not present
      in metallothionein mice. Diabetes depressed PS, +/-dL/dt and caffeine-induced
      Ca2+ release, as well as prolonged TR90 and Ca2+ decay in male FVB mice, whereas
      it only reduced PS in female FVB mice. These diabetic dysfunctions were nullified
      by metallothionein in both sexes. Females displayed elevated Akt phosphorylation
      and reduced c-Jun phosphorylation. Diabetes dampened Akt phosphorylation in male
      FVB mice and enhanced c-Jun in both sexes. Diabetes-induced alterations in Akt
      phosphorylation and c-Jun were abolished by metallothionein. The sex difference
      in Akt phosphorylation but not c-Jun levels was reversed by metallothionein.
      These data indicate that antioxidant capacity plays an important role in sex
      differences in both intrinsic and diabetic cardiomyocyte contractile properties
      possibly related to phosphorylation of Akt and c-Jun.

PMID- 16410377
TI  - Frequency-dependent contractile response of isolated cardiac trabeculae under
      hypo-, normo-, and hyperthermic conditions.
AB  - The body is from time to time exposed to nonnormothermic conditions; both hypo-
      and hyperthermia can occur as a result of external (environment) or internal
      (pathogens, allergens) stressors. To preserve life under hypo- and hyperthermic
      conditions, adequate perfusion of vital organs is mandated. Although cardiac
      output regulation under hyperthermic conditions has been studied, the mechanical
      response of basic contractile function of the myocardium itself is incompletely
      understood. Accordingly, we set out to test mechanical output of isolated
      myocardium under hyperthermic conditions and to compare the results with the hypo
      and normothermic response in the same tissue. We observed that, in absence of a
      frequency change, developed force decreased markedly. At a physiological normal
      stimulation rate of 6 Hz, developed force decreases to 67.2 +/- 2.6% at 42
      degrees C compared with 37 degrees C. In addition, twitch timing characteristics
      also accelerate, allowing for a faster relaxation; time from peak tension to 50%
      relaxation is approximately 23% faster (from 31.4 +/- 2.6 to 24.4 +/- 1.7 ms).
      Although this faster relaxation in turn prevents a steep increase in diastolic
      tension at high frequencies, the very fast calcium kinetics now prevent a more
      complete activation of the myofilaments, resulting in a lower twitch-force
      maximum at hyperthermic conditions. Even at maximal beta-adrenergic stimulation,
      developed force is well below levels reached at physiological temperature.

PMID- 16410378
TI  - Human ventilatory responsiveness to hypoxia is unrelated to maximal aerobic
      capacity.
AB  - Ventilatory responsiveness to hypoxia (HVR) has been reported to be different
      between highly trained endurance athletes and healthy sedentary controls.
      However, a linkage between aerobic capacity and HVR has not been a universal
      finding. The purpose of this study was to examine the relationship between HVR
      and maximal oxygen consumption (VO2 max) in healthy men with a wide range of
      aerobic capacities. Subjects performed a HVR test followed by an incremental
      cycle test to exhaustion. Participants were classified according to their maximal
      aerobic capacity. Those with a VO2 max of >or=60 ml x kg(-1) x min(-1) were
      considered highly trained (n = 13); those with a VO2 max of 50-60 ml x kg(-1) x
      min(-1) were considered moderately-trained (n = 18); and those with a VO2 max of
      <50 ml x kg(-1) x min(-1) were considered untrained (n = 24). No statistical
      differences were detected between the three groups for HVR (P > 0.05), and the
      HVR values were variable within each group (range: untrained = 0.28-1.61,
      moderately trained = 0.23-2.39, and highly trained = 0.08-1.73 l x min.%arterial
      O2 saturation(-1)). The relationship between HVR and VO2 max was not
      statistically significant (r = -0.1723; P > 0.05). HVR was also unrelated to
      maximal minute ventilation and ventilatory equivalents for O2 and CO2. We found
      that a spectrum of hypoxic ventilatory control is present in well-trained
      endurance athletes and moderately and untrained men. We interpret these
      observations to mean that other factors are more important in determining hypoxic
      ventilatory control than physical conditioning per se.

PMID- 16410379
TI  - Sex-based effects on the distribution of NK cell subsets in response to exercise
      and carbohydrate intake in adolescents.
AB  - Carbohydrate (CHO) supplementation and female sex independently influence the
      natural killer (NK) cell response to acute exercise. Consequently, this study
      sought to elucidate sex-based differences in the distribution of NK cell subsets
      (i.e., CD56dim and CD56bright) in response to exercise and CHO intake. Twenty-two
      healthy 14-yr-old girls (n = 11) and boys (n = 11) cycled for 60 min at 70%
      maximal oxygen consumption while drinking 6% CHO (CT) or flavored water (WT).
      Blood was collected at rest, during exercise (30 and 60 min), and during recovery
      (30 and 60 min) to identify CD3- CD56dim and CD3- CD56bright NK cells. The
      activation marker CD69 was also determined on CD3- CD56+ cells. CD56dim
      responses, expressed as proportions or cell counts, were greater (P < or = 0.01)
      in girls by 67 and 105%, respectively. CD56bright cell counts (P = 0.006), but
      not CD56bright proportions (P = 0.89), were greater in girls by 82%. Both CD56dim
      and CD56bright subset responses, expressed as proportions or cell counts, were
      lower (P < or = 0.01) in CT vs. WT by 33-36%. The CD56bright-to-CD56dim ratio
      decreased at 30 min of exercise but increased during recovery (P < 0.001), with
      no effect of sex or CHO. Regardless of trial, CD3- CD56+ cells expressed
      approximately 18% higher levels of CD69 during recovery in girls but not boys (P
      = 0.03), despite similar proportions and counts of CD69+ cells. These results
      demonstrate sex-based differences in the distribution of NK cell subsets and
      activation status in response to exercise, but not CHO intake, and further
      support the need to control for sex in exercise immunology studies.

PMID- 16410380
TI  - Contribution of thermal and nonthermal factors to the regulation of body
      temperature in humans.
AB  - The set point has been used to define the regulated level of body temperature,
      suggesting that displacements of core temperature from the set point initiate
      heat production (HP) and heat loss (HL) responses. Human and animal experiments
      have demonstrated that the responses of sweating and shivering do not coincide at
      a set point but rather establish a thermoeffector threshold zone.
      Neurophysiological studies have demonstrated that the sensor-to-effector pathways
      for HP and HL overlap and, in fact, mutually inhibit each other. This reciprocal
      inhibition theory, presumably reflecting the manner in which thermal factors
      contribute to homeothermy in humans, does not incorporate the effect of
      nonthermal factors on temperature regulation. The present review examines the
      actions of these nonthermal factors within the context of neuronal models of
      temperature regulation, suggesting that examination of these factors may provide
      further insights into the nature of temperature regulation. It is concluded that,
      although there is no evidence to doubt the existence of the HP and HL pathways
      reciprocally inhibiting one another, it appears that such a mechanism is of
      little consequence when comparing the effects of nonthermal factors on the
      thermoregulatory system, since most of these factors seem to exert their
      influence in the region after the reciprocal cross-inhibition. At any given
      moment, both thermal and several nonthermal factors will be acting on the
      thermoregulatory system. It may, therefore, not be appropriate to dismiss the
      contribution of either when discussing the regulation of body temperature in
      humans.

PMID- 16410381
TI  - Alpha-adrenergic receptor-mediated restraint of skeletal muscle blood flow during
      prolonged exercise.
AB  - Sympathetic nervous system restraint of skeletal muscle blood flow during dynamic
      exercise has been well documented. However, whether sympathetic restraint of
      muscle blood flow persists and is constant throughout prolonged exercise has not
      been established. We hypothesized that both alpha1- and alpha2-adrenergic
      receptors would restrain skeletal muscle blood flow throughout prolonged constant
      load exercise and that the restraint would increase as a function of exercise
      duration. Mongrel dogs were instrumented chronically with transit-time flow
      probes on the external iliac arteries and an indwelling catheter in a branch of
      the femoral artery. Flow-adjusted doses of selective alpha1- (prazosin) and
      alpha2-adrenergic receptor (rauwolscine) antagonists were infused after 5, 30,
      and 50 min of treadmill exercise at 3 and 6 miles/h. During mild-intensity
      exercise (3 miles/h), prazosin infusion resulted in a greater (P < 0.05) increase
      in vascular conductance (VC) after 5 [42% (SD 6)], compared with 30 [28% (SD 6)]
      and 50 [28% (SD 8)] min of running. In contrast, prazosin resulted in a similar
      increase in VC after 5 [29% (SD 10)], 30 [24% (SD 9)], and 50 [22% (SD 9)] min of
      moderate-intensity (6 miles/h) exercise. Rauwolscine infusion resulted in a
      greater (P < 0.05) increase in VC after 5 [39% (SD 14)] compared with 30 [26% (SD
      9)] and 50 [22% (SD 4)] min of exercise at 3 miles/h. Rauwolscine infusion
      produced a similar increase in VC after 5 [19% (SD 3)], 30 [15% (SD 6)], and 50
      [16% (SD 2)] min of exercise at 6 miles/h. These results suggest that the ability
      of alpha1- and alpha2-adrenergic receptors to produce vasoconstriction and
      restrain blood flow to active muscles may be influenced by both the intensity and
      duration of exercise.

PMID- 16410382
TI  - Diaphyseal bone formation in murine tibiae in response to knee loading.
AB  - Mechanical stimulation is critical for bone architecture and bone mass. The aim
      of this study was to examine the effects of mechanical loads applied to the knee.
      The specific question was whether loads applied to the tibial epiphysis would
      enhance bone formation in the tibial diaphysis. In C57/BL/6 mice, loads of 0.5 N
      were applied for 3 min per day for 3 days at 5, 10, or 15 Hz. Bone samples were
      harvested 13 days after the last loading. The strains were measured 13 +/- 2
      microstrains at 5 Hz in the diaphysis. The histomorphometric data in the
      diaphysis clearly showed enhanced bone formation. First, compared with nonloaded
      control the cross-sectional cortical area was increased by 11% at 5 Hz and 8% at
      10 Hz (both P < 0.05). Second, the cortical thickness was elevated by 12% at 5 Hz
      (P < 0.01) and 8% at 10 Hz (P < 0.05). Third, mineralizing surface (MS/BS),
      mineral apposition rate (MAR), and bone formation rate (BFR/BS) were increased at
      5 Hz (P < 0.01 for MS/BS; P < 0.001 for MAR and BFR/BS) and at 10 Hz (P < 0.05
      for MS/BS; P < 0.01 for MAR and BFR/BS). Bone formation was enhanced more
      extensively in the medial side than the lateral or the posterior side. The
      results reveal that knee loading is an effective means to enhance bone formation
      in the tibial diaphysis in a loading-frequency dependent manner without inducing
      significant in situ strain at the site of bone formation.

PMID- 16410383
TI  - FMS-like tyrosine kinase 3 in normal hematopoiesis and acute myeloid leukemia.
AB  - Ligand-mediated activation of the FMS-like tyrosine kinase 3 (FLT3) receptor is
      important for normal proliferation of primitive hematopoietic cells. However,
      activating mutations in FLT3 induce ligand-independent downstream signaling that
      promotes oncogenesis through pathways involved in proliferation, differentiation,
      and survival. FLT3 mutations are identified as the most frequent genetic
      abnormality in acute myeloid leukemia and are also observed in other leukemias.
      Multiple small-molecule inhibitors are under development to target aberrant FLT3
      activity that confers a poor prognosis in patients.

PMID- 16410384
TI  - Ciliated cells differentiated from mouse embryonic stem cells.
AB  - In the present study, we demonstrated that the mouse embryonic stem cells were
      differentiated into ciliated epithelial cells, with characteristics of normal
      ciliated cells. These cells expressed ciliary marker proteins, such as beta
      tubulin IV and hepatocyte nuclear factor-3/forkhead homolog 4 (HFH-4), and
      processed microtubules were arranged in the 9 + 2 structure, which is the same
      specific alignment observed in normal ciliary microtubules. The cilia of these
      cells were beating at a frequency of 17-20 Hz. The differentiated embryoid bodies
      (EBs) containing these ciliated cells expressed respiratory marker genes such as
      thyroid transcription factor-1 and surfactant protein-C. For the induction of
      ciliated cells, culture of EBs in serum-free medium during the initial 2 days of
      the attachment was indispensable. When EBs were treated with bone morphogenetic
      proteins, the expression of HFH-4 was decreased, and the ciliated cells were
      scarcely differentiated. Previous methods for inducing ciliated cells in vitro
      from embryonic or adult tissues involved an air-liquid interface. The system used
      in this study more closely mimics the normal development of ciliated cells; thus,
      an added advantage of the system is as a tool for studying the differentiation
      mechanism of normal ciliated epithelial cells.

PMID- 16410385
TI  - Na+/H+ exchanger regulatory factor-1 is a hematopoietic ligand for a subset of
      the CD34 family of stem cell surface proteins.
AB  - CD34 and its relatives, podocalyxin and endoglycan, comprise a family of surface
      sialomucins expressed by hematopoietic stem/progenitor cells and vascular
      endothelia. Recent data suggest that they serve as either pro- or antiadhesion
      molecules depending on their cellular context and their post-translational
      modifications. In addition, their ability to function as blockers of adhesion may
      be further regulated by their subcellular localization in membrane microdomains
      via activation-dependent linkage with the actin cytoskeleton. To gain further
      insights into the function and regulation of CD34-type molecules, we sought to
      identify the intracellular ligands that govern their localization. Using both
      genetic and biochemical approaches, we have identified the Na(+)/H(+) exchanger
      regulatory factor-1 (NHERF-1) as a selective ligand for podocalyxin and
      endoglycan but not for the closely related CD34. Furthermore, we show that NHERF
      1 is expressed by all c-kit(+) /lineage marker(-)/Sca-1(+) cells, which are known
      to express podocalyxin and have long-term repopulating abilities. Finally, we
      show that these proteins relocalize and colocalize in response to cytokine
      signaling. The results suggest that this cytosolic adaptor protein may be
      important for mobilization of CD34-type proteins in the plasma membrane and may
      thereby regulate their ability to block or enhance hematopoietic cell adhesion.

PMID- 16410386
TI  - Serial transplantations in nonobese diabetic/severe combined immunodeficiency
      mice of transduced human CD34+ cord blood cells: efficient oncoretroviral gene
      transfer and ex vivo expansion under serum-free conditions.
AB  - Stable oncoretroviral gene transfer into hematopoietic stem cells (HSCs) provides
      permanent genetic disease correction. It is crucial to transplant enough
      transduced HSCs to compete with and replace the defective host hemopoiesis. To
      increase the number of transduced cells, the role of ex vivo expansion was
      investigated. For a possible clinical application, all experiments were carried
      out in serum-free media. A low-affinity nerve growth factor receptor (LNGFR)
      pseudotyped murine retroviral vector was used to transduce cord blood CD34(+)
      cells, which were then expanded ex vivo. These cells engrafted up to three
      generations of serially transplanted nonobese diabetic/severe combined
      immunodeficiency mice: 54.26% +/- 5.59%, 19.05% +/- 2.01%, and 6.15% +/- 5.16%
      CD45(+) cells from primary, secondary, and tertiary recipient bone marrow,
      respectively, were LNGFR(+). Repopulation in secondary and tertiary recipients
      indicates stability of transgene expression and long-term self-renewal potential
      of transduced HSCs, suggesting that retroviral gene transfer into HSCs, followed
      by ex vivo expansion, could facilitate long-term engraftment of genetically
      modified HSCs.

PMID- 16410387
TI  - Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord
      blood, or adipose tissue.
AB  - Mesenchymal stem cells (MSCs) represent a promising tool for new clinical
      concepts in supporting cellular therapy. Bone marrow (BM) was the first source
      reported to contain MSCs. However, for clinical use, BM may be detrimental due to
      the highly invasive donation procedure and the decline in MSC number and
      differentiation potential with increasing age. More recently, umbilical cord
      blood (UCB), attainable by a less invasive method, was introduced as an
      alternative source for MSCs. Another promising source is adipose tissue (AT). We
      compared MSCs derived from these sources regarding morphology, the success rate
      of isolating MSCs, colony frequency, expansion potential, multiple
      differentiation capacity, and immune phenotype. No significant differences
      concerning the morphology and immune phenotype of the MSCs derived from these
      sources were obvious. Differences could be observed concerning the success rate
      of isolating MSCs, which was 100% for BM and AT, but only 63% for UCB. The colony
      frequency was lowest in UCB, whereas it was highest in AT. However, UCB-MSCs
      could be cultured longest and showed the highest proliferation capacity, whereas
      BM-MSCs possessed the shortest culture period and the lowest proliferation
      capacity. Most strikingly, UCB-MSCs showed no adipogenic differentiation
      capacity, in contrast to BM- and AT-MSCs. Both UCB and AT are attractive
      alternatives to BM in isolating MSC: AT as it contains MSCs at the highest
      frequency and UCB as it seems to be expandable to higher numbers.

PMID- 16410389
TI  - Migration of bone marrow and cord blood mesenchymal stem cells in vitro is
      regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met
      axes and involves matrix metalloproteinases.
AB  - Human mesenchymal stem cells (MSCs) are increasingly being considered in cell
      based therapeutic strategies for regeneration of various organs/tissues. However,
      the signals required for their homing and recruitment to injured sites are not
      yet fully understood. Because stromal-derived factor (SDF)-1 and hepatocyte
      growth factor (HGF) become up-regulated during tissue/organ damage, in this study
      we examined whether these factors chemoattract ex vivo-expanded MSCs derived from
      bone marrow (BM) and umbilical cord blood (CB). Specifically, we investigated the
      expression by MSCs of CXCR4 and c-met, the cognate receptors of SDF-1 and HGF,
      and their functionality after early and late passages of MSCs. We also determined
      whether MSCs express matrix metalloproteinases (MMPs), including membrane type 1
      (MT1)-MMP, matrix-degrading enzymes that facilitate the trafficking of
      hematopoietic stem cells. We maintained expanded BM- or CB-derived MSCs for up to
      15-18 passages with monitoring of the expression of 1) various tissue markers
      (cardiac and skeletal muscle, neural, liver, and endothelial cells), 2)
      functional CXCR4 and c-met, and 3) MMPs. We found that for up to 15-18 passages,
      both BM- and CB-derived MSCs 1) express mRNA for cardiac, muscle, neural, and
      liver markers, as well as the vascular endothelial (VE) marker VE-cadherin; 2)
      express CXCR4 and c-met receptors and are strongly attracted by SDF-1 and HGF
      gradients; 3) express MMP-2 and MT1-MMP transcripts and proteins; and 4) are
      chemo-invasive across the reconstituted basement membrane Matrigel. These in
      vitro results suggest that the SDF-1-CXCR4 and HGF-c-met axes, along with MMPs,
      may be involved in recruitment of expanded MSCs to damaged tissues.

PMID- 16410388
TI  - Establishment and applications of epstein-barr virus-based episomal vectors in
      human embryonic stem cells.
AB  - Human embryonic stem (hES) cells are capable of unlimited cell proliferation yet
      maintain the potential to differentiate into many cell types. Here we reported an
      Epstein-Barr virus (EBV)-based vector system used to improve transfection
      efficiency in hES cells. Plasmids containing oriP, the latent replication origin
      of EBV, can be propagated stably as episomal DNA in human cells that express the
      EBV nuclear antigen 1 (EBNA1), which binds to oriP and functions as the trans
      acting replication initiator. It was reported that the EBV replicon could harbor
      a DNA fragment of up to 330 kilobase pairs. Plasmids containing an enhanced green
      fluorescent protein (EGFP)/puromycin resistance gene cassette along with or
      without oriP were used to transfect hES cells that stably express EBNA1. The
      presence of oriP moderately increased the transient transfection efficiency and
      more importantly it elevated the stable transfection efficiency by approximately
      1,000-fold as compared with oriP-minus plasmids. The oriP plasmid as episomal DNA
      and green fluorescent protein expression in hES cells was maintained for months
      in the presence of drug selection and gradually lost (2%-4% per cell doubling) in
      the absence of selection. The presence of EBNA1 did not interfere with the hES
      cell properties or differentiation we tested and could maintain stable EGFP
      expression during differentiation. In addition to transgene expression, the EBV
      vector system could effectively enhance the RNA interference efficiency in hES
      cells. Thus, the EBV vector system that allows a large DNA insert and sustained
      expression of transgene or small hairpin RNA will enhance basic and translational
      research using hES cells.

PMID- 16410390
TI  - Transplantation of human hematopoietic stem cells into ischemic and growing
      kidneys suggests a role in vasculogenesis but not tubulogenesis.
AB  - Transplantation of murine bone marrow-derived stem cells has been reported
      recently to promote regeneration of the injured kidney. We investigated the
      potential of human adult CD34(+) progenitor cells to undergo renal
      differentiation once xenotransplanted into ischemic and developing kidneys.
      Immunostaining with human-specific antibodies for tubular cells (broad-spectrum
      cytokeratin), endothelial cells (CD31, PECAM), stromal cells (vimentin), and
      hematopoietic cells (pan-leukocyte CD45) demonstrated that although kidney
      ischemia enhanced engraftment of human cells, they were mostly hematopoietic
      cells (CD45(+)) residing in the interstitial spaces. Few other engrafted cells
      demonstrated an endothelial phenotype (human CD31(+)in morphologically appearing
      peritubular capillaries), but no evidence of tubular or stromal cells of human
      origin was found. Upregulation of SDF1 and HIF1 transcript levels in the ischemic
      kidneys might explain the diffuse engraftment of CD45(+)cells following injury.
      Similarly, when embryonic kidneys rudiments were co-transplanted with human
      CD34(+)cells in mice, we found both human CD45(+)and CD31(+)cells in the
      periphery of the developing renal grafts, whereas parenchymal elements failed to
      stain. In addition, human CD34(+)cells had no effect on kidney growth and
      differentiation. This first demonstration of human CD34(+)stem cell
      transplantation into injured and developing kidneys indicates that these cells do
      not readily acquire a tubular phenotype and are restricted mainly to
      hematopoietic and, to a lesser extent, to endothelial lineages. Efforts should be
      made to identify additional stem cell sources applicable for kidney growth and
      regeneration.

PMID- 16410391
TI  - The immunogenicity of human adipose-derived cells: temporal changes in vitro.
AB  - Regenerative medical techniques will require an abundant source of human adult
      stem cells that can be readily available at the point of care. The ability to use
      unmatched allogeneic stem cells will help achieve this goal. Since adipose tissue
      represents an untapped reservoir of human cells, we have compared the immunogenic
      properties of freshly isolated, collagenase-digested human adipose tissue-derived
      stromal vascular fraction cells (SVFs) relative to passaged, plastic-adherent
      adipose-derived stem cells (ASCs). Parallel studies have shown that adherence to
      plastic and subsequent expansion of human adipose-derived cells selects for a
      relatively homogeneous cell population based on immunophenotype. Consistent with
      these findings, the presence of hematopoietic-associated markers (CD11a, CD14,
      CD45, CD86, and histocompatible locus antigen-DR [HLA-DR]) detected on the
      heterogeneous SVF cell population decreased upon subsequent passage of the ASCs.
      In mixed lymphocyte reactions (MLRs), SVFs, and early passage ASCs stimulated
      proliferation by allogeneic responder T cells. In contrast, the ASCs beyond
      passage P1 failed to elicit a response from T cells. Indeed, late passage ASCs
      actually suppressed the MLR response. Although these results support the
      feasibility of allogeneic human ASC transplantation, confirmatory in vivo animal
      studies will be required.

PMID- 16410392
TI  - HOXB4 overexpression promotes hematopoietic development by human embryonic stem
      cells.
AB  - Human embryonic stem cells (hESCs) are a potential source of hematopoietic cells
      for therapeutic transplantation and can provide a model for human hematopoiesis.
      Culture of hESCs on murine stromal layers or in stromal-free conditions as
      embryoid bodies results in low levels of hematopoietic cells. Here we demonstrate
      that overexpression of the transcription factor HOXB4 considerably augments
      hematopoietic development of hESCs. Stable HOXB4-expressing hESC clones were
      generated by lipofection and could be maintained in the undifferentiated state
      for prolonged passages. Moreover, differentiation of hESCs as embryoid bodies in
      serum-containing medium without the use of additional cytokines led to sequential
      expansion of first erythroid and then myeloid and monocytic progenitors from day
      10 of culture. These cells retained the capacity to develop into formed blood
      elements during in vitro culture. Consistent with the development of committed
      hematopoietic cells, we observed the expression of transcription factors known to
      be critical for hematopoietic development. We thus demonstrate successful use of
      enforced gene expression to promote the differentiation of hESCs into a
      terminally differentiated tissue, thereby revealing an important role for HOXB4
      in supporting their in vitro development along the hematopoietic pathway.

PMID- 16410393
TI  - Effects of Delta1 and Jagged1 on early human hematopoiesis: correlation with
      expression of notch signaling-related genes in CD34+ cells.
AB  - It has been shown that Notch signaling mediated by ligands of both Jagged and
      Delta families expands the hematopoietic stem cell compartment while blocking or
      delaying terminal myeloid differentiation. Here we show that Delta1- and Jagged1
      expressing stromal cells have distinct effects on the clonogenic and
      differentiation capacities of human CD34(+) CD38(+) cells. Jagged1 increases the
      number of bipotent colony-forming unit-granulocyte macrophage (CFU-GM) and
      unipotent progenitors (CFU-granulocytes and CFU-macrophages), without
      quantitatively affecting terminal cell differentiation, whereas Delta1 reduces
      the number of CFU-GM and differentiated monocytic cells. Expression analysis of
      genes coding for Notch receptors, Notch targets, and Notch signaling modulators
      in supernatant CD34(+) cells arising upon contact with Jagged1 and Delta1 shows
      dynamic and differential gene expression profiles over time. At early time
      points, modest upregulation of Notch1, Notch3, and Hes1 was observed in Jagged1
      CD34(+) cells, whereas those in contact with Delta1 strikingly upregulated Notch3
      and Hes1. Later, myeloid progenitors with strong clonogenic potential emerging
      upon contact with Jagged1 upregulated Notch1 and Deltex and downregulated Notch
      signaling modulators, whereas T/NK progenitors originated by Delta1 strikingly
      upregulated Notch3 and Deltex and, to a lesser extent, Hes1, Lunatic Fringe, and
      Numb. Together, the data unravel previously unrecognized expression patterns of
      Notch signaling-related genes in CD34(+) CD38(+) cells as they develop in Jagged1
      or Delta1-stromal cell environments, which appear to reflect sequential
      maturational stages of CD34(+) cells into distinct cell lineages.

PMID- 16410394
TI  - Identification and characterization of hemoangiogenic progenitors during
      cynomolgus monkey embryonic stem cell differentiation.
AB  - We identified intermediate-stage progenitor cells that have the potential to
      differentiate into hematopoietic and endothelial lineages from nonhuman primate
      embryonic stem (ES) cells. Sequential fluorescence-activated cell sorting and
      immunostaining analyses showed that when ES cells were cultured in an OP9
      coculture system, both lineages developed after the emergence of two
      hemoangiogenic progenitor-bearing cell fractions, namely, vascular endothelial
      growth factor receptor (VEGFR)-2(high) CD34(-) and VEGFR-2(high) CD34(+) cells.
      Exogenous vascular endothelial growth factor increased the proportion of VEGFR
      2(high) cells, particularly that of VEGFR-2(high) CD34(+) cells, in a dose
      dependent manner. Although either population of VEGFR-2(high) cells could
      differentiate into primitive and definitive hematopoietic cells (HCs), as well as
      endothelial cells (ECs), the VEGFR-2(high) CD34(+) cells had greater
      hemoangiogenic potential. Both lineages developed from VEGFR-2(high) CD34(-)or
      VEGFR-2(high) CD34(+) precursor at the single-cell level, which strongly supports
      the existence of hemangioblasts in these cell fractions. Thus, this culture
      system allows differentiation into the HC and EC lineages to be defined by
      surface markers. These observations should facilitate further studies both on
      early developmental processes and on regeneration therapies in human.

PMID- 16410395
TI  - Bone marrow cells transdifferentiate to cardiomyocytes when introduced into the
      embryonic heart.
AB  - Since rates of cardiomyocyte generation in the embryo are much higher than within
      the adult, we explored whether the embryonic heart would serve as useful
      experimental system for examining the myocardial potential of adult stem cells.
      Previously, we reported that the long-term culturing of adult mouse bone marrow
      produced a cell population that was both highly enriched for macrophages and
      cardiac competent. In this study, the myocardial potential of this cell
      population was analyzed in greater detail using the embryonic chick heart as
      recipient tissue. Experiments involving the co-incubation of labeled bone marrow
      cells with embryonic heart tissue showed that bone marrow (BM) cells incorporated
      into the myocardium and immunostained for myocyte proteins. Reverse transcription
      polymerase chain reaction analysis demonstrated that the heart tissue induced
      bone marrow cells to express the differentiated cardiomyocyte marker alpha
      cardiac myosin heavy chain. The cardiomyocyte conversion of the bone marrow cells
      was verified by harvesting donor cells from mice that were genetically labeled
      with a myocardial-specific beta-galactosidase reporter. Embryonic hearts exposed
      to the transgenic bone marrow in culture exhibited significant numbers of beta
      galactosidase-positive cells, indicating the presence of bone marrow-derived
      cells that had converted to a myocardial phenotype. Furthermore, when transgenic
      mouse BM cells were injected into living chick embryos, donor cells incorporated
      into the developing heart and exhibited a myocardial phenotype.
      Immunofluorescence analysis demonstrated that donor BM cells exhibiting myocyte
      markers contained only nuclei from mouse cells, indicating that differentiation
      and not cell fusion was the predominant mechanism for the acquisition of a
      myocyte phenotype. These data confirm that adult mouse bone marrow contain cells
      with the ability to form cardiomyocytes. In addition, the predominance of the
      macrophage phenotype within the donor bone marrow cell population suggests that
      transdifferentiation of immune response cells may play a role in cellular
      regeneration in the adult.

PMID- 16410396
TI  - Ventilatory response to hyperoxia in newborn mice heterozygous for the
      transcription factor Phox2b.
AB  - Heterozygous mutations of the transcription factor PHOX2B have been found in most
      patients with central congenital hypoventilation syndrome, a rare disease
      characterized by sleep-related hypoventilation and impaired chemosensitivity to
      sustained hypercapnia and sustained hypoxia. PHOX2B is a master regulator of
      autonomic reflex pathways, including peripheral chemosensitive pathways. In the
      present study, we used hyperoxic tests to assess the strength of the peripheral
      chemoreceptor tonic drive in Phox2b+/-newborn mice. We exposed 69 wild-type and
      67 mutant mice to two hyperoxic tests (12-min air followed by 3-min 100% O2) 2
      days after birth. Breathing variables were measured noninvasively using whole
      body flow plethysmography. The initial minute ventilation decrease was larger in
      mutant pups than in wild-type pups: -37% (SD 13) and -25% (SD 18), respectively,
      P<0.0001. Furthermore, minute ventilation remained depressed throughout O2
      exposure in mutants, possibly because of their previously reported impaired CO2
      chemosensitivity, whereas it returned rapidly to the normoxic level in wild-type
      pups. Hyperoxia considerably increased total apnea duration in mutant compared
      with wild-type pups (P=0.0001). A complementary experiment established that body
      temperature was not influenced by hyperoxia in either genotype group and,
      therefore, did not account for genotype-related differences in the hyperoxic
      ventilatory response. Thus partial loss of Phox2b function by heterozygosity did
      not diminish the tonic drive from peripheral chemoreceptors.

PMID- 16410397
TI  - Perinatal photoperiod organizes adult immune responses in Siberian hamsters
      (Phodopus sungorus).
AB  - Individuals of many nontropical rodent species display reproductive,
      immunological, and somatic responses to day length. In general, short day (SD)
      lengths inhibit reproduction and enhance immune function in the laboratory when
      all other conditions are held constant. Most studies to date have focused on
      seasonal variation in immune function in adulthood. However, perinatal
      photoperiods also communicate critical day length information and serve to
      establish a developmental trajectory appropriate for the time of year.
      Nontropical rodents born early in the breeding season undergo rapid reproductive
      development, presumably to promote mating success during their first reproductive
      season. Rodents born late in the breeding season suspend somatic growth and
      puberty until the following vernal breeding season. We tested the hypothesis that
      perinatal day lengths have similar enduring effects on the immune system of
      rodents. Siberian hamsters (Phodopus sungorus) were maintained prenatally and
      until weaning (21 days) in either SDs (8 h light:16 h dark) or long days (LD) (16
      h light:8 h dark), then they were weaned into either the opposite photoperiod or
      maintained in their natal photoperiod, forming four groups (LD-LD, LD-SD, SD-LD,
      and SD-SD). After 8-wk in these conditions, cell-mediated immune activity was
      compared among groups. SD-SD hamsters of both sexes enhanced immune function
      relative to all other groups. The reproductive effects of perinatal photoperiod
      were not evident by the end of the experiment; circulating testosterone and
      cortisol sampled at the end of the experiment reflected the postweaning, but not
      the perinatal photoperiod. This experiment demonstrates long-lasting
      organizational effects of perinatal photoperiod on the rodent immune system and
      indicates that photoperiod-induced changes in the immune system are dissociable
      from changes in the reproductive system.

PMID- 16410398
TI  - Green tea extract improves running endurance in mice by stimulating lipid
      utilization during exercise.
AB  - A series of polyphenols known as catechins are abundant in green tea, which is
      consumed mainly in Asian countries. The effects of catechin-rich green tea
      extract (GTE) on running endurance and energy metabolism during exercise in
      BALB/c mice were investigated. Mice were divided into four groups: nonexercise
      control, exercise control (Ex-cont), exercise+0.2% GTE, and exercise+0.5% GTE
      groups. Treadmill running time to exhaustion, plasma biochemical parameters,
      skeletal muscle glycogen content, beta-oxidation activity, and malonyl-CoA
      content immediately after exercise were measured at 8-10 wk after the initiation
      of the experiment. Oxygen consumption and respiratory exchange ratio were
      measured using indirect calorimetry. Running times to exhaustion in mice fed 0.5%
      GTE were 30% higher than in Ex-cont mice and were accompanied by a lower
      respiratory exchange ratio, higher muscle beta-oxidation activity, and lower
      malonyl-CoA content. In addition, muscle glycogen content was high in the GTE
      group compared with the Ex-cont group. Plasma lactate concentrations in mice fed
      GTE were significantly lower after exercise, concomitant with an increase in free
      fatty acid concentrations. Catechins, which are the main constituents of GTE, did
      not show significant effects on peroxisome proliferator-activated receptor-alpha
      or delta-dependent luciferase activities. These results suggest that the
      endurance-improving effects of GTE were mediated, at least partly, by increased
      metabolic capacity and utilization of fatty acid as a source of energy in
      skeletal muscle during exercise.

PMID- 16410399
TI  - Expression of the long form of the prolactin receptor in magnocellular oxytocin
      neurons is associated with specific prolactin regulation of oxytocin neurons.
AB  - Magnocellular neurons of the supraoptic (SON) and paraventricular nuclei (PVN)
      show considerable plasticity during pregnancy and lactation. Prolactin receptors
      (PRL-R) have been identified in both these nuclei. The aim of this study was to
      investigate the cell type(s) expressing mRNA for the long form of prolactin
      receptor (PRL-R(L)) and to determine whether patterns of expression change during
      pregnancy and lactation. In addition, we examined effects of prolactin on
      excitability of oxytocin and vasopressin neurons. Sections from brains of
      nonpregnant, pregnant, and lactating rats were hybridized with an 35S-labeled
      probe to label PRL-R(L) mRNA together with digoxigenin-labeled probes to detect
      either oxytocin or vasopressin mRNA. In the SON, PRL-R(L) mRNA was predominantly
      colocalized with oxytocin mRNA, with over 80% of oxytocin neurons positive for
      PRL-R(L) mRNA. Very few (<10%) vasopressin neurons expressed PRL-R(L) mRNA. In
      the PVN, PRL-R(L) mRNA was also predominantly found in oxytocin neurons, and the
      proportion of PRL-R(L)-positive oxytocin neurons increased significantly during
      pregnancy and lactation. As in the SON, relatively few vasopressin cells
      contained PRL-R(L) mRNA. For in vivo electrophysiology, nonpregnant rats were
      anesthetized, and then extracellular single neuron activity was recorded in
      identified oxytocin and vasopressin neurons. After a period of baseline
      recording, the effect of prolactin (1 microg i.c.v.) on firing rate was examined.
      Prolactin treatment of nonpregnant rats induced a significant decrease in firing
      rates of oxytocin neurons. There was no effect of prolactin on the activity of
      vasopressin neurons. Together, these data provide strong evidence that prolactin
      directly and specifically regulates activity of oxytocin neurons.

PMID- 16410400
TI  - Kupffer cell-generated PGE2 triggers the febrile response of guinea pigs to
      intravenously injected LPS.
AB  - Because the onset of fever induced by intravenously (i.v.) injected bacterial
      endotoxic lipopolysaccharides (LPS) precedes the appearance in the bloodstream of
      pyrogenic cytokines, the presumptive peripheral triggers of the febrile response,
      we have postulated previously that, in their stead, PGE2 could be the peripheral
      fever trigger because it appears in blood coincidentally with the initial body
      core temperature (Tc) rise. To test this hypothesis, we injected Salmonella
      enteritidis LPS (2 microg/kg body wt i.v.) into conscious guinea pigs and
      measured their plasma levels of LPS, PGE2, TNF-alpha, IL-1beta, and IL-6 before
      and 15, 30, 60, 90, and 120 min after LPS administration; Tc was monitored
      continuously. The animals were untreated or Kupffer cell (KC) depleted; the
      essential involvement of KCs in LPS fever was shown previously. LPS very promptly
      (<10 min) induced a rise of Tc that was temporally correlated with the elevation
      of plasma PGE2. KC depletion prevented the Tc and plasma PGE2 rises and slowed
      the clearance of LPS from the blood. TNF-alpha was not detectable in plasma until
      30 min and in IL-1beta and IL-6 until 60 min after LPS injection. KC depletion
      did not alter the times of appearance or magnitudes of rises of these cytokines,
      except TNF-alpha, the maximal level of which was increased approximately twofold
      in the KC-depleted animals. In a follow-up experiment, PGE2 antiserum
      administered i.v. 10 min before LPS significantly attenuated the febrile response
      to LPS. Together, these results support the view that, in guinea pigs, PGE2
      rather than pyrogenic cytokines is generated by KCs in immediate response to i.v.
      LPS and triggers the febrile response.

PMID- 16410401
TI  - Orexin neuron-mediated skeletal muscle vasodilation and shift of baroreflex
      during defense response in mice.
AB  - We have previously shown that some features of the defense response, such as
      increases in arterial blood pressure (AP), heart rate (HR), and ventilation were
      attenuated in prepro-orexin knockout (ORX-KO) mice. Here, we examined whether the
      same was true in orexin neuron-ablated [orexin/ataxin-3 transgenic mice (ORX/ATX
      Tg)] mice. In addition, we examined other features of the defense response:
      skeletal muscular vasodilation and shift of baroreceptor reflex. In both
      anesthetized and conscious conditions, basal AP in ORX/ATX-Tg mice was
      significantly lower by approximately 20 mmHg than in wild-type (WT) controls, as
      was the case in ORX-KO mice. The difference in AP disappeared after treatment
      with an alpha-blocker but not with a beta-blocker, indicating lower sympathetic
      vasoconstrictor outflow. Stimulation of the perifornical area (PFA) in urethane
      anesthetized ORX/ATX-Tg mice elicited smaller and shorter-lasting increases in
      AP, HR, and ventilation, and skeletal muscle vasodilation than in WT controls. In
      addition, air jet stress-induced elevations of AP and HR were attenuated in
      conscious ORX/ATX-Tg mice. After pretreatment with a beta-blocker, atenolol,
      stimulation of PFA suppressed phenylephrine (50 microg/kg iv)-induced bradycardia
      (DeltaHR=-360+/-29 beats/min without PFA stimulation vs. -166+/-26 during
      stimulation) in WT. This demonstrated the resetting of the baroreflex. In ORX/ATX
      Tg mice, however, no significant suppression was observed (-355+/-16 without
      stimulation vs. -300+/-30 during stimulation). The present study provided further
      support for our hypothesis that orexin-containing neurons in PFA play a role as a
      master switch to activate multiple efferent pathways of the defense response and
      also operate as a regulator of basal AP.

PMID- 16410402
TI  - Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated
      by losartan but not by amlodipine.
AB  - Mitochondrial dysfunction is associated with cardiovascular damage; however, data
      on a possible association with kidney damage are scarce. Here, we aimed at
      investigating whether 1) kidney impairment is related to mitochondrial
      dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can
      reverse potential mitochondrial changes in hypertension. Eight-week-old male
      spontaneously hypertensive rats (SHR) received water containing losartan (40
      mg.kg-1.day-1, SHR+Los), amlodipine (3 mg.kg-1.day-1, SHR+Amlo), or no additions
      (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular
      and tubulointerstitial damage, systolic blood pressure, and proteinuria were
      higher, and creatinine clearance was lower in SHR vs. SHR+Los and WKY. In
      SHR+Amlo, blood pressure was similar to WKY, kidney function was similar to SHR,
      and renal lesions were lower than in SHR, but higher than in SHR+Los. In kidney
      mitochondria from SHR and SHR+Amlo, membrane potential, nitric oxide synthase,
      manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling
      protein-2 content were lower than in SHR+Los and WKY. In SHR and SHR+Amlo,
      mitochondrial H2O2 production was higher than in SHR+Los and WKY. Renal
      glutathione content was lower in SHR+Amlo relative to SHR, SHR+Los, and WKY. In
      SHR and SHR+Amlo, glutathione was relatively more oxidized than in SHR+Los and
      WKY. Tubulointerstitial alpha-smooth muscle actin labeling was inversely related
      to manganese-superoxide dismutase activity and uncoupling protein-2 content.
      These findings suggest that oxidant stress is associated with renal mitochondrial
      dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an
      additional or alternative way to explain some of the beneficial effects of AT1
      receptor antagonists.

PMID- 16410403
TI  - Inverse regulation of preproendothelin-1 and endothelin-converting enzyme-1beta
      genes in cardiac cells by mechanical load.
AB  - Mechanical stretch and para- and/or autocrine factors, including endothelin-1,
      induce hypertrophy of cardiac myocytes and proliferation of fibroblasts. To
      investigate the effect of mechanical load on endothelin-1 production and
      endothelin system gene expression in neonatal rat ventricular myocytes and
      fibroblasts, we exposed cells to cyclic mechanical stretch in vitro (0.5 Hz, 10
      25% elongation, from 1 min to 24 h). Endothelin-1 peptide levels were measured
      from culture media of myocytes and fibroblasts and human umbilical vein
      endothelial cells (positive control) by specific radioimmunoassay.
      Preproendothelin-1 promoter activity was measured via transfection of reporter
      plasmids and mRNA levels with Northern blot analysis or quantitative RT-PCR.
      Activity of extracellular signal-regulated kinase was quantified with specific
      kinase assay. We found that stretching of myocytes activated preproendothelin-1
      gene expression, including promoter activation, transient mRNA level increases,
      and augmented endothelin-1 secretion. In contrast, preproendothelin-1 gene
      expression was inhibited in stretched fibroblasts. Endothelin-converting enzyme
      1beta mRNA levels elevated in stretched fibroblasts but decreased in stretched
      myocytes. Endothelin receptor type A mRNA levels declined in stretched myocytes,
      whereas levels were below detection in fibroblasts. Stretch activated
      extracellular signal-regulated kinase in myocytes, and when the kinase activity
      was pharmacologically inhibited, the preproendothelin-1 induction was suppressed.
      Transient overexpression of mitogen-activated ERK-activating kinase-1 induced
      preproendothelin-1 promoter in myocytes. In summary, mechanical stretch
      distinctly regulates endothelin system gene expression in cardiac myocytes and
      fibroblasts. The inhibition of the endothelin system may affect cardiac
      mechanotransduction and therefore provides an approach in treatment of load
      induced cardiac pathology.

PMID- 16410404
TI  - A novel partial agonist of the A(1)-adenosine receptor and evidence of receptor
      homogeneity in adipocytes.
AB  - This study characterizes the receptor binding and functional effects of CVT-3619
      [2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2
      fluorophenylthio)methyl]-oxolane-3,4-diol], a novel N(6)-5' -substituted
      adenosine analog and A(1) -adenosine receptor (A(1) AdoR) agonist, on rat
      epididymal and inguinal adipocytes and on the isolated heart and compares these
      effects with those caused by the full agonist N(6) -cyclopentyladenosine (CPA).
      In addition, the hypothesis that adipocyte A(1)AdoR are a heterogeneous
      population with regard to their affinities for ligands was tested. CVT-3619 was
      10-100-fold selective for A(1)AdoR versus other AdoR and bound to adipocyte
      membranes with high (K(H) = 14 nM) and low (K = 5.4 microM) affinities. CVT-3619
      reduced cyclic AMP content and release of nonesterified fatty acids from
      epididymal adipocytes with IC(50) values of 6 and 44 nM, respectively. CVT-3619
      was a partial agonist relative to CPA to reduce lipolysis in epididymal and
      inguinal adipocytes. CVT-3619 did not change atrial rate in rat heart and caused
      a small (6-ms) prolongation of the stimulus-to-His bundle interval without
      causing atrioventricular block in guinea pig heart (effects mediated by
      A(1)AdoR), whereas CPA caused atrioventricular block and near cessation of atrial
      electrical activity. CVT-3619 increased coronary conductance (effect mediated by
      A(2A)AdoR) only at concentrations > or =10 microM. Rat epididymal adipocyte
      A(1)AdoR had similar affinities for the antagonist 8-cyclopentyl-1,3
      dipropylxanthine in the presence of three dissimilar A AdoR agonists (2-chloro
      N(6) -cyclopentyladenosine, N(6) -sulfophenyladenosine, and N-5' 
      ethylcarboxamidoadenosine) as determined by Schild analysis. It was concluded
      that rat epididymal adipocyte A(1)AdoR are a homogeneous receptor population with
      regard to affinities for ligands and that CVT-3619 is a partial agonist with
      selectivity for A(1)AdoR and inhibition of lipolysis.

PMID- 16410405
TI  - Role of site-specific binding to plasma albumin in drug availability to brain.
AB  - Many studies have reported greater drug uptake into brain than that predicted
      based upon existing models using the free fraction (f(u)) of drug in arterial
      serum. To explain this difference, circulating plasma proteins have been
      suggested to interact with capillary membrane in vivo to produce a conformational
      change that favors net drug dissociation and elevation of f(u). Albumin, the
      principal binding protein in plasma, has two main drug binding sites, Sudlow I
      and II. We tested this hypothesis using drugs that bind selectively to either
      site I (warfarin) or site II (ibuprofen), as well as mixed ligands that have
      affinity for both sites (tolbutamide and valproate). Brain uptake was determined
      in the presence and absence of albumin using the in situ rat brain perfusion
      technique. Unidirectional brain uptake transfer constants (K(in)) were measured
      and compared with those predicted using the modified Kety-Crone-Renkin model:
      K(in) = F(1-e(-f(u) x PS(u)/F)), where F is perfusion flow and PS(u) is the
      permeability-surface area product to free drug of brain capillaries. The results
      demonstrated good agreement between measured and predicted K(in) over a 100-fold
      range in perfusion fluid albumin concentration using albumin from three different
      species (i.e., human, bovine, and rat), as well as whole-rat serum. K(in)
      decreased in the presence of albumin in direct proportion to perfusion fluid f(u)
      with constant PS(u). The results show that brain uptake of selected Sudlow site I
      and II ligands matches that predicted by the modified Kety-Crone-Renkin model
      with no evidence for enhanced dissociation.

PMID- 16410406
TI  - Theophylline improves early allograft function in rat kidney transplantation.
AB  - Several previous studies have demonstrated a beneficial effect of the adenosine
      receptor (AdoR) antagonist theophylline in different forms of acute renal failure
      in laboratory animals and in humans. Therefore, we wanted to test whether
      theophylline can also improve impaired allograft function following ischemia
      reperfusion injury in experimental kidney transplantation (KT). Orthotopic
      transplantation of the left kidney was performed from Fisher 344 into Lewis rats.
      All transplanted rats received daily cyclosporine (5 mg/kg). The effect of
      theophylline treatment (10 mg/kg) on graft function was compared with appropriate
      controls on day 5 after KT by assessment of glomerular filtration rate (GFR)
      (inulin clearance). On day 5, GFR of allografts in control rats was 0.23 +/- 0.05
      ml/min/g kidney weight (n = 10) compared with 0.50 +/- 0.09 ml/min/g in rats
      receiving theophylline (n = 9, p < 0.01), representing a 2-fold increase in GFR.
      Renal AdoR A(1) mRNA content was significantly increased in both KT groups
      compared with their respective control groups, whereas mRNA of AdoR A(2a), A(2b),
      and A(3) were found to be unchanged. Theophylline did not affect significantly
      interstitial infiltration of the graft by monocytes/macrophages and T-cells.
      Likewise, serum cytokines [interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor
      alpha] and erythropoietin plasma levels were not different among the allograft
      groups. The present study demonstrates that theophylline remarkably improved
      early renal allograft function in rats undergoing KT without influencing cytokine
      serum patterns or tissue inflammation. Since theophylline is a commonly used
      medication in humans, clinical studies in patients undergoing KT are warranted.

PMID- 16410407
TI  - Molecular determinants in the second intracellular loop of the 5
      hydroxytryptamine-1A receptor for G-protein coupling.
AB  - This study provides the first comprehensive evidence that the second
      intracellular loop C-terminal domain (Ci2) is critical for receptor-G protein
      coupling to multiple responses. Although Ci2 is weakly conserved, its role in 5
      hydroxytryptamine-1A (5-HT1A) receptor function was suggested by the selective
      loss of Gbetagamma-mediated signaling in the T149A-5-HT1A receptor mutant. More
      than 60 point mutant 5-HT1A receptors in the alpha-helical Ci2 sequence
      (143DYVNKRTPRR152) were generated. Most mutants retained agonist binding and were
      tested for Gbetagamma signaling to adenylyl cyclase II or phospholipase C and
      Galphai coupling to detect constitutive and agonist-induced Gi/Go coupling.
      Remarkably, most point mutations markedly attenuated 5-HT1A signaling, indicating
      that the entire Ci2 domain is critical for receptor G-protein coupling. Six
      signaling phenotypes were observed: wild-type-like, Galphai-coupled/weak
      Gbetagamma-coupled, Gbetagamma-uncoupled, Gbetagamma-selective coupled,
      uncoupled, and inverse coupling. Our data elucidate specific roles of Ci2
      residues consistent with predictions based on rhodopsin crystal structure. The
      absolute coupling requirement for lysine, arginine, and proline residues is
      consistent with a predicted amphipathic alpha-helical Ci2 domain that is kinked
      at Pro150. Polar residues (Thr149, Asn146) located in the externally oriented
      positively charged face were required for Gbetagamma but not Galphai coupling,
      suggesting a direct interface with Gbetagamma subunits. The hydrophobic face
      includes the critical Tyr144 that directs the specificity of coupling to both
      Gbetagamma and Galphai pathways. The key coupling residues Tyr144/Lys147 (Ci2)
      are predicted to orient internally, forming hydrogen and ionic bonds with
      Asp133/Arg134 (Ni2 DRY motif) and Glu340 (Ci3) to stabilize the Gprotein coupling
      domain. Thus, the 5-HT1A receptor Ci2 domain determines Gbetagamma specificity
      and stabilizes Galphai-mediated signaling.

PMID- 16410408
TI  - A novel mechanism of action of methyl-2-cyano-3,12 dioxoolean-1,9 diene-28-oate:
      direct permeabilization of the inner mitochondrial membrane to inhibit electron
      transport and induce apoptosis.
AB  - Methyl-2-cyano-3,12 dioxoolean-1,9 diene-28-oate (CDDO-Me) is a synthetic
      oleanolic acid derivative that displays antitumorigenic and anti-inflammatory
      activities, and we have previously reported that this agent potently activates
      the intrinsic apoptotic pathway in leukemia cells. In this study, we demonstrate
      that mitochondrial dysfunction induced by CDDO-Me is mediated by direct
      permeabilization of the inner mitochondrial membrane, which results in the rapid
      depletion of mitochondrial glutathione (GSXm), loss of cardiolipin, and
      inhibition of mitochondrial respiration. More importantly, we demonstrate that in
      addition to activating the intrinsic apoptotic pathway, the mitochondrial effects
      of CDDO-Me may mediate its anti-inflammatory activity by modulating the
      generation of superoxide anion (O2*). It is noteworthy that CDDO-Me did not
      increase the generation of O2* and pretreatment of leukemia cells with CDDO-Me
      prevented the increase of this reactive oxygen species elicited by inhibition of
      complex I or III in the absence of de novo protein synthesis. CDDO-Me, but not
      other inhibitors of respiration, induced a time- and dose-dependent, cyclosporin
      A-independent permeability transition (PT) of isolated mitochondria that was
      sensitive to sulfhydryl antioxidants but not to EDTA. PT induced by CDDO-Me and
      Ca2+ was accompanied by loss of GSXm, suggesting that the increased permeability
      of the inner mitochondrial membrane facilitates the loss of this antioxidant.
      Finally, transmission electron microscopy revealed that CDDO-Me rapidly induced
      caspase-independent mitochondrial swelling and loss of inner membrane structure
      before the release of cytochrome c. Taken together, our results indicate that
      CDDO-Me is a novel mitochondriotoxic agent that induces apoptosis and inhibits
      mitochondrial electron transport via perturbations in inner mitochondrial
      membrane integrity.

PMID- 16410409
TI  - The interpretation of morphogen gradients.
AB  - Morphogens act as graded positional cues that control cell fate specification in
      many developing tissues. This concept, in which a signalling gradient regulates
      differential gene expression in a concentration-dependent manner, provides a
      basis for understanding many patterning processes. It also raises several
      mechanistic issues, such as how responding cells perceive and interpret the
      concentration-dependent information provided by a morphogen to generate precise
      patterns of gene expression and cell differentiation in developing tissues. Here,
      we review recent work on the molecular features of morphogen signalling that
      facilitate the interpretation of graded signals and attempt to identify some
      emerging common principles.

PMID- 16410410
TI  - bZIP transcription factor interactions regulate DIF responses in Dictyostelium.
AB  - The signalling molecule DIF-1 is required for normal cell fate choice and
      patterning in Dictyostelium. To understand how these developmental processes are
      regulated will require knowledge of how cells receive and respond to the DIF-1
      signal. Previously, we have described a bZIP transcription factor, DimA, which is
      required for cells to respond to DIF-1. However, it was unknown whether DimA
      activity is required to activate the DIF response pathway in certain cells or is
      a component of the response pathway itself. In this study, we describe the
      identification of a DimA-related bZIP transcription factor, DimB. Rapid changes
      in the subcellular localisation of both DimA and DimB in response to DIF-1
      suggest that they are directly downstream of the DIF-1 signal. Genetic and
      biochemical interactions between DimA and DimB provides evidence that their
      ability to regulate diverse targets in response to DIF-1 is partly due to their
      ability to form homo- and heterodimeric complexes. DimA and DimB are therefore
      direct regulators of cellular responses to DIF-1.

PMID- 16410412
TI  - Neurogenin 2 is required for the development of ventral midbrain dopaminergic
      neurons.
AB  - Proneural genes are crucial regulators of neurogenesis and subtype specification
      in many areas of the nervous system; however, their function in dopaminergic
      neuron development is unknown. We report that proneural genes have an intricate
      pattern of expression in the ventricular zone of the ventral midbrain, where
      mesencephalic dopaminergic neurons are generated. Neurogenin 2 (Ngn2) and Mash1
      are expressed in the ventral midline, while Ngn1, Ngn2 and Mash1 are co-localized
      more laterally in the ventricular zone. Ngn2 is also expressed in an intermediate
      zone immediately adjacent to the ventricular zone at the ventral midline. To
      examine the function of these genes, we analyzed mutant mice in which one or two
      of these genes were deleted (Ngn1, Ngn2 and Mash1) or substituted (Mash1 in the
      Ngn2 locus). Our results demonstrate that Ngn2 is required for the
      differentiation of Sox2(+) ventricular zone progenitors into Nurr1(+) postmitotic
      dopaminergic neuron precursors in the intermediate zone, and that it is also
      likely to be required for their subsequent differentiation into tyrosine
      hydroxylase-positive dopaminergic neurons in the marginal zone. Although Mash1
      normally has no detectable function in dopaminergic neuron development, it could
      partially rescue the generation of dopaminergic neuron precursors in the absence
      of Ngn2. These results demonstrate that Ngn2 is uniquely required for the
      development of midbrain dopaminergic neurons.

PMID- 16410411
TI  - Ras-dva, a member of novel family of small GTPases, is required for the anterior
      ectoderm patterning in the Xenopus laevis embryo.
AB  - Ras-like small GTPases are involved in the regulation of many processes essential
      for the specification of the vertebrate body plan. Recently, we identified the
      gene of novel small GTPase Ras-dva, which is specifically expressed at the
      anterior margin of the neural plate of the Xenopus laevis embryo. Now, we
      demonstrate that Ras-dva and its homologs in other species constitute a novel
      protein family, distinct from the previously known families of small GTPases. We
      show that the expression of Ras-dva begins during gastrulation throughout the
      anterior ectoderm and is activated by the homeodomain transcription factor Otx2;
      however, later on, Ras-dva expression is inhibited in the anterior neural plate
      by another homeodomain factor Xanf1. Downregulation of Ras-dva functioning by the
      dominant-negative mutant or by the antisense morpholino oligonucleotides results
      in severe malformations of the forebrain and derivatives of the cranial placodes.
      Importantly, although the observed abnormalities can be rescued by co-injection
      of the Ras-dva mRNA, they cannot be rescued by the mRNA of the closest Ras-dva
      homolog from another family of small GTPases, Ras. This fact indicates functional
      specificity of the Ras-dva signaling pathway. At the molecular level,
      downregulation of Ras-dva inhibits the expression of several regulators of the
      anterior neural plate and folds patterning, such as Otx2, BF-1 (also known as
      Foxg1), Xag2, Pax6, Slug and Sox9, and interferes with FGF8 signaling within the
      anterior ectoderm. By contrast, expression of the epidermal regulator BMP4 and
      its target genes, Vent1, Vent2b and Msx1, is upregulated. Together, the data
      obtained indicate that Ras-dva is an essential component of the signaling network
      that patterns the early anterior neural plate and the adjacent ectoderm in the
      Xenopus laevis embryos.

PMID- 16410413
TI  - The Sonic hedgehog pathway independently controls the patterning, proliferation
      and survival of neuroepithelial cells by regulating Gli activity.
AB  - During CNS development, the proliferation of progenitors must be coordinated with
      the pattern of neuronal subtype generation. In the ventral neural tube, Sonic
      hedgehog acts as a long range morphogen to organise the pattern of cell
      differentiation by controlling the activity of Gli transcription factors. Here,
      we provide evidence that the same pathway also acts directly at long range to
      promote the proliferation and survival of progenitor cells. Blockade of Shh
      signaling or inhibition of Gli activity results in cell autonomous decreases in
      progenitor proliferation and survival. Conversely, positive Gli activity promotes
      proliferation and rescues the effects of inhibiting Shh signaling. Analysis of
      neural cells indicates that Shh/Gli signaling regulates the G1 phase of cell
      cycle and the expression of the anti-apoptotic factor Bcl2. Furthermore, Shh
      signaling independently regulates patterning, proliferation and survival of
      neural cells, thus Shh/Gli activity couples these separate cellular responses of
      progenitors to coordinate neural development.

PMID- 16410414
TI  - Massive loss of Cajal-Retzius cells does not disrupt neocortical layer order.
AB  - Cajal-Retzius (CR) cells, the predominant source of reelin in developing
      neocortex, are thought to be essential for the inside out formation of
      neocortical layers. Fate mapping revealed that a large population of neocortical
      CR cells arises from the cortical hem. To investigate the function of CR cells,
      we therefore genetically ablated the hem. Neocortical CR cells were distributed
      beneath the pial surface in control mice, but were virtually absent in hem
      ablated mice from embryonic day (E) 10.5 until birth. CR cells derived from other
      sources did not invade the neocortical primordium to compensate for hem loss. We
      predicted that neocortical layers would be inverted in hem-ablated animals, as in
      reeler mice, deficient in reelin signaling. Against expectation, layers showed
      the standard order. Low levels of reelin in the cortical primordium, or diffusion
      of reelin from other sites, may have allowed lamination to proceed. Our findings
      indicate, however, that the sheet of reelin-rich CR cells that covers the
      neocortical primordium is not required to direct layer order.

PMID- 16410416
TI  - Using the Internet to build community capacity for healthy public policy.
AB  - An interactive Web site and e-mail campaign became the primary focus of a
      coalition's community mobilization strategy to advocate for changes to the local
      smoking bylaw in a large Canadian urban center. This article presents the
      findings of an Internet survey of 2,200 Internet mailing list recipients in which
      26% (n=605) submitted responses. Findings from four focus groups of the survey
      respondents (n=28) are also reported. The survey found that a majority of the
      mailing list respondents (66.1%) contacted the city council during the campaign.
      Only 35.8% of respondents had contacted a city council member prior to this
      campaign. As a result of their participation in the Internet campaign, 50.6%
      stated that they were more likely to get involved in future civic issues. These
      findings were confirmed by focus groups that found increased capacity for
      political involvement on this issue as well as capacity for future social and
      political action.

PMID- 16410417
TI  - Improving our application of the health education code of ethics.
AB  - The Health Education Code of Ethics was designed to provide a framework of shared
      values within which health education might be practiced. However, an informal
      survey conducted on a limited sample in November 2004 indicated that ethics and
      how to apply the code are topics not readily taught formally within all health
      education programs. There is, however, an expressed interest among health
      educators in understanding the code and its application. Because of the immense
      import of ethics, affecting responsible professional conduct at all levels, this
      article is designed to introduce the topic to health education practitioners who
      have had little formal exposure to ethics curricula, as well as to faculty who
      would like to teach this subject. The authors specifically review several
      resources that might be especially helpful in fostering a better understanding of
      this essential but often underestimated aspect of health education practice and
      research, namely, its ethical application.

PMID- 16410418
TI  - Benefits of standardized diabetes and hypertension screening forms at community
      screening events.
AB  - The objectives of this project were to (a) assess hypertension and diabetes
      screening data collection practices and guidelines and (b) develop and test
      standardized screening forms for use at minority community- and faith-based
      screening events. Project Phase I involved resource assessment and the
      development of a set of screening forms and guidelines containing a core data set
      for both hypertension and diabetes. These were then tested during Phase II at
      predetermined community based screening events throughout the United States.
      Community- and faith-based health screening programs are important in reaching
      and informing individuals in selected communities about their health and health
      risks. This study demonstrated the development of a standard tool that was
      effective in conducting African American community-based screening programs for
      hypertension and diabetes by community-based organizations. These activities are
      effective to obtain standardized information on individuals within the
      communities served.

PMID- 16410419
TI  - Perceived versus actual risk for hypertension and diabetes in the African
      American community.
AB  - Hypertension and diabetes mellitus are leading health concerns in the United
      States. Despite a disproportionate burden of both conditions among African
      Americans, it is estimated that 44% of diabetes cases and one quarter of
      hypertension cases within this population are undiagnosed. Lack of awareness of
      the risk of these conditions may hinder preventive efforts and the adoption of
      positive lifestyle changes. Based on the findings from a pilot study to develop
      and standardize uniform screening forms for hypertension and diabetes, this
      article reports on the perceived risk versus actual risk of developing these
      conditions among primarily African American participants using a community-based
      screening tool. Each form assessed both perceived and actual risk of diabetes and
      hypertension, respectively. A total of 265 hypertension and 225 diabetes
      screening forms were randomly selected from eight sites across the country. The
      risk perception of the overall study sample was similar to its actual risk for
      developing either condition. However, a significant proportion of individuals who
      scored at high risk for diabetes or hypertension were unaware of their risk for
      these conditions. These results suggest the need for developing culturally
      relevant interventions, public health education, and policies that address the
      risk misperceptions among this group.

PMID- 16410420
TI  - Our lives were healthier before: focus groups with African American, American
      Indian, Hispanic/Latino, and Hmong people with diabetes.
AB  - Focus groups were conducted to explore health-related beliefs and experiences of
      African American, Hispanic/Latino, American Indian, and Hmong people with
      diabetes and engage community members in improving diabetes care and education
      for these populations. Eighty participants attended 12 focus groups, 3 per
      population. Major themes were loss of health attributed to modern American
      lifestyles, lack of confidence in the medical system, and the importance of
      spirituality. Participants recommended improvements in the areas of health care,
      diabetes education, social support, and community action. Their recommendations
      emphasize the importance of respectful, knowledgeable health care providers;
      culturally responsive diabetes education for people with diabetes and their
      families; and broad-based community action. These recommendations align with
      current public health priorities and medical knowledge. It is proposed that
      healthy traditions from diverse populations can be leveraged to improve the
      health of all people with diabetes.

PMID- 16410421
TI  - Cultural relevancy of a diabetes prevention nutrition program for African
      American women.
AB  - Diabetes among African American women is a pressing health concern, yet there are
      few evaluated culturally relevant prevention programs for this population. This
      article describes a case study of the Eat Well Live Well Nutrition Program, a
      community-based, culturally specific diabetes prevention nutrition program for
      African American women. The stages of change theory and principles from community
      organization guided the development of the program. Health education strategies,
      including participatory development and program delivery by peer educators, were
      applied to promote cultural relevance. Results indicated that overall
      participants (90%) believed the program to be culturally relevant and were very
      satisfied with the program (82%). Cultural relevancy was significantly associated
      with greater program satisfaction and changes in dietary patterns when
      controlling for the number of sessions attended. Conclusions suggest that
      participatory strategies can be effective in designing culturally specific
      prevention programs for African American women.

PMID- 16410422
TI  - Salud Para Su Corazon-NCLR: a comprehensive Promotora outreach program to promote
      heart-healthy behaviors among hispanics.
AB  - This article describes results of year-1 implementation of the Salud Para Su
      Corazon (Health For Your Heart)-National Council of la Raza (NCLR) promotora (lay
      health worker) program for promoting heart-healthy behaviors among Latinos.
      Findings of this community outreach initiative include data from promotora
      pledges and self-skill behaviors, cardiovascular disease risk factors of Latino
      families, family heart-health education delivery, and program costs associated
      with promotora time. Participation included 29 trained promotoras serving 188
      families from three NCLR affiliates in Escondido, California; Chicago, Illinois;
      and Ojo Caliente, New Mexico. Using several evaluation tools, the results showed
      that the promotora approach worked based on evidence obtained from the following
      indicators: changes in promotora's pre-post knowledge and performance skills,
      progress toward their pledge goals following training, recruiting and teaching
      families, providing follow-up, and organizing or participating in community
      events. Strengths and limitations of the promotora model approach are also
      discussed.

PMID- 16410423
TI  - Web-based technical assistance and training to promote community tobacco control
      policy change.
AB  - In 1998 the tobacco industry was released of claims that provided monetary relief
      for states. A significant expansion of tobacco control activity in many states
      created a need to develop local capacity. Technical assistance and training for
      new and experienced staff became a significant challenge for tobacco control
      leadership. In Colorado, this challenge was addressed in part through the
      development of a technical assistance and training Web site designed for local
      tobacco control staff and coalition members. Researchers, technical Web site
      development specialists, state health agency, and state tobacco control coalition
      staff collaborated to develop, promote, and test the efficacy of this Web site.
      The work group embodied a range of skills including tobacco control, Web site
      technical development, marketing, training, and project management. Persistent
      marketing, updating of Web site content, and institutionalizing it as a principal
      source of information and training were key to use by community coalition
      members.

PMID- 16410424
TI  - Developing a community health promotion agenda for a managed care organization.
AB  - Coordination and collaboration between organizations interested in promoting the
      health of the populations they serve can potentially help to ensure that key
      services are provided as well as augment the efforts beyond that which could be
      accomplished by each organization alone. Understanding the perspectives of each
      organization can facilitate development of health promotion initiatives that will
      be of mutual benefit. In Maryland, when a Medicaid managed care program was
      initiated, Memoranda of Understanding were signed between each managed care
      organization (MCO) and each of the 24 local health departments; many stipulated
      that the parties will coordinate on community health issues. This report
      describes a telephone survey of the health departments that was performed by one
      MCO to better understand the interests and expectations of the health departments
      and discusses a process for developing a community health promotion agenda for an
      MCO.

PMID- 16410426
TI  - The development and validation of a coding protocol to measure change in tobacco
      control newspaper coverage.
AB  - The national ASSIST newspaper coding protocol model was used as a template to
      adapt a system for measuring tobacco-related newspaper coverage in Colorado
      newspapers. Over a 3-month period, tobacco-related articles were clipped from 180
      daily and weekly newspapers. Variables coded included adaptations of the original
      ASSIST categories. During development and testing, additional variables were
      added to make the protocol more comprehensive and sensitive to tobacco policy
      media coverage. Inter-coder reliabilities were calculated for all non-static
      variables using Cohen's kappa. Disagreements were resolved through group
      discussions. Two rounds of testing achieved ratings above .70 for all variables.
      The protocol improves dramatically upon the ASSIST model by providing greater
      breadth and depth of analysis and more sensitivity to the nuances of newspaper
      coverage of tobacco-related issues. Given its simplicity, the protocol could also
      prove valuable for anti-tobacco advocacy groups who wish to track the changes in
      public and media opinions.

PMID- 16410425
TI  - Parental literacy and infant health: an evidence-based healthy start
      intervention.
AB  - Syracuse Healthy Start, a federally funded infant mortality prevention project in
      Onondaga County, New York, has undertaken a range of interventions to address
      parental low literacy as a risk factor for infant mortality. A growing number of
      studies advocate for health-related information that is easy to read, of a low
      literacy level, and culturally appropriate. Creation of an evidence-based public
      health intervention involves analyzing local data, reviewing published studies,
      assessing available materials, initiating programmatic interventions, and
      evaluating the outcomes. Preparing health educational materials that are clear,
      culturally sensitive, and at appropriate reading levels follows Paulo Freire's
      lead in empowering the disadvantaged to positively affect their health and the
      health of their infants toward the reduction of infant mortality.

PMID- 16410427
TI  - Developing effective written communication and advocacy skills in entry-level
      health educators through writing-intensive program planning methods courses.
AB  - Written communication is a requisite skill for practitioners in the field of
      health education. Advocacy skills are now considered to be both a professional
      competency and an ethical responsibility. Given that many advocacy strategies
      involve written communication, it makes sense that the skills of writing and
      advocacy be developed concomitantly and within a writing-intensive class. The
      purposes of this article are twofold: (a) to describe the role of writing
      intensive program planning methods courses in the development of written
      communication and advocacy skills in entry-level health educators and (b) to
      suggest strategies for planning, implementing, and assessing writing-intensive
      assignments and instructional activities designed to develop students' written
      communication and advocacy skills. Multiple examples of writing assignments are
      presented that can be used in helping students in developing their critical
      thinking, writing, and advocacy skills.

PMID- 16410428
TI  - Rethinking the bystander role in school violence prevention.
AB  - Public concerns about school shootings and safety draw attention to the role
      bystanders can play in preventing school violence. Although school violence
      prevention plans are often required, there is little guidance about whether these
      should address the roles of bystanders and what actions bystanders should take in
      different circumstances, from more common instances of bullying and fighting to
      rare, but potentially lethal, threats and use of weapons. Literature pertaining
      to bystanders is reviewed and applied to the school setting. The definition of
      bystander is expanded, including parents, teachers, and other school staff as
      well as youths and those who have information about potential violence as well as
      those who witness its occurrence. Barriers preventing bystanders from taking
      positive actions are discussed. The authors call on health promotion researchers
      and practitioners to work with school communities to identify norms, attitudes,
      and outcome expectancies that shape bystander behaviors to inform prevention
      efforts.

PMID- 16410429
TI  - Use of body-mind-spirit dimensions for the development of a wellness behavior and
      characteristic inventory for college students.
AB  - The purpose of this study was to use a body-mind-spirit model to measure wellness
      behaviors and characteristics and develop the Body-Mind-Spirit Wellness Behavior
      and Characteristic Inventory (BMS-WBCI) for college students. The first study of
      this two-part project included item generation and factor analysis using 1,000
      college students with average loadings of .64, .51, and .58 for the Spirit, Mind,
      and Body factors, respectively. Using a minimum 4.0 Eigenvalue criterion, the
      factors accounted for 30% of item variance. The second study phase included
      validity testing using TestWell (college version), a meal screener, and construct
      physical activity question with 141 students. The BMS-WBCI dimensions had high,
      positive correlations with all appropriate TestWell subscales. The Body dimension
      significantly correlated with the By-Meal Screener and physical activity
      question. Factor split-half reliabilities ranged from .73 to .84 and alpha
      coefficients ranged from .75 to .92. Implications and utilization of the BMSWBCI
      for college students are discussed.

PMID- 16410430
TI  - Prostate cancer screening decision making under controversy: implications for
      health promotion practice.
AB  - Prostate cancer is a major health problem for U.S. men and is characterized by
      paradoxes and controversies. Despite the wide availability of the prostate
      specific antigen (PSA) test, prostate cancer screening remains a controversial
      practice mainly because the direct impact of screening on mortality is not yet
      proven. As the relative value of screening, early detection, and treatment
      strategies continue to be debated, glaring racial-ethnic disparities persist with
      African American men experiencing excess morbidity and mortality and
      demonstrating the lowest screening rates among racial-ethnic groups. Given the
      prevailing controversy, uncertainty, and known disparities, how can health
      education messages be framed to assist men and their family members? This article
      highlights the ethnic disparities, paradoxes, and controversies of prostate
      cancer and identifies critical challenges and opportunities for health educators
      and clinical practitioners. Implications for health promotion communications and
      informed decision making in this era of uncertainty are discussed.

PMID- 16410431
TI  - Healing fractured families: parents' and elders' perspectives on the impact of
      colonization and youth suicide prevention in a pacific northwest American Indian
      tribe.
AB  - Suicide rates among American Indian youth in the United States are two to three
      times the national average. Risk factors for American Indian youth include
      depression, alcohol use, hopelessness and stress, and family conflict, abuse,
      poverty, and instability. In this descriptive study, the authors aimed to obtain
      parents' and elders' perspectives on community needs and to identify strengths on
      which the community might build to reduce youth suicide risk. Data were collected
      from focus groups with 40 American Indian parents and from individual interviews
      with 9 American Indian elders. The major task participants addressed was holding
      the family together and healing intergenerational pains. Topics parents discussed
      were holding onto cultural values, holding the family together, getting through
      school, and getting a job. These findings substantiate previous research and
      provide useful information for the design of culturally appropriate family or
      community-based interventions to prevent American Indian youth suicide.

PMID- 16410432
TI  - Aboriginal healing: regaining balance and culture.
AB  - This ethnographic study explored the question, How do urban-based First Nations
      peoples use healing traditions to address their health issues? The objectives
      were to examine how Aboriginal traditions addressed health issues and explore the
      link between such traditions and holism in nursing practice. Data collection
      consisted of individual interviews, participant observations, and field notes.
      Three major categories that emerged from the data analysis were: following a
      cultural path, gaining balance, and sharing in the circle of life. The global
      theme of healing holistically included following a cultural path by regaining
      culture through the use of healing traditions; gaining balance in the four realms
      of spiritual, emotional, mental, and physical health; and sharing in the circle
      of life by cultural interactions between Aboriginal peoples and non-Aboriginal
      health professionals. Implications for practice include incorporating the
      concepts of balance, holism, and cultural healing into the health care services
      for diverse Aboriginal peoples.

PMID- 16410433
TI  - Voluntary HIV counseling and testing: knowledge and practices in a rural South
      African village.
AB  - The purpose of the study was to identify themes related to voluntary counseling
      and testing services in a rural South African village. Qualitative research
      methods using grounded theory approach were used. Data were collected from 20
      informants. Participants demonstrated knowledge of the availability of voluntary
      HIV counseling and testing services in the area; however participants did not
      utilize the services unless they had signs and symptoms suggesting possible HIV
      infection. Health providers have a responsibility to ensure that individuals get
      tested before they are infected so as to educate them about ways to protect
      themselves against HIV infection.

PMID- 16410434
TI  - Beyond asylum: implications for nursing and health care delivery for Afghan
      refugees in Australia.
AB  - Descriptions of the refugee experience, together with an analysis of access, use,
      and appropriateness of mental and physical health services as perceived by
      members of the Afghan immigrant or refugee community living in New South Wales
      (NSW), Australia, are reported in this article. Using focus groups and
      semistructured interviews in a variety of settings, the study included 13 key
      informants and 25 general informants, together with health care agencies
      providing services to the Afghans and organizations providing resources. Analysis
      of interviews with Afghan people revealed a number of themes. These include
      emotional responses to trauma, migration, and resettlement experiences; culture
      specific health maintenance strategies; barriers impeding access to and
      appropriateness of Australian health care services; and informant-suggested
      strategies to enhance accessibility and the appropriateness of health care and
      community services. These findings are significant and have relevance for
      improving the quality of culture-specific health care for the Afghan community in
      NSW Australia.

PMID- 16410435
TI  - Psychological and mental illness among elder immigrants from the former Soviet
      Union.
AB  - The study examined the cultural context of psychological illness among elder
      immigrants from the former Soviet Union (FSU). Kleinman's (1980) explanatory
      model of illness and Leininger's theory of culture care (1997) provided the
      conceptual framework for the study. Participant Observations were conducted in an
      Adult Day Care Center and Senior Housing. Twenty-three key informants and 10
      general informants participated. The social and historical context of the FSU
      influenced the meaning, attitudes, expressions, and coping strategies toward
      psychological and mental illness. Cultural stigma influenced the attribution of
      cause, somatic expression of symptoms, and attitudes toward seeking professional
      help. Psychological illness was unrecognized, whereas mental illness was viewed
      as lack of dusha (inner strength and moral character). Group differences were
      evident with ethnicity as a significant influence in symptom recognition,
      expression, and attitude toward seeking professional help.

PMID- 16410436
TI  - Being different and vulnerable: experiences of immigrant African women who have
      been circumcised and sought maternity care in Sweden.
AB  - The purpose of the study was to explore the encounters with the health care
      system in Sweden of women from Somalia, Eritrea, and Sudan who have been
      genitally cut. A qualitative study was performed through interviews with 22 women
      originally from Somalia, Sudan, and Eritrea who were living in Sweden. The women
      experienced being different and vulnerable, suffering from being abandoned and
      mutilated, and they felt exposed in the encounter with the Swedish health care
      personnel and tried to adapt to a new cultural context. The results of this study
      indicate a need for more individualized, culturally adjusted care and support and
      a need for systematic education about female genital cutting for Swedish health
      care workers.

PMID- 16410437
TI  - Racial disparities in testicular cancer: impact on health promotion.
AB  - The present study sought to determine to what extent there was a difference in
      ethnicity between age and stage of testicular cancer. The sample, from National
      Cancer Institute data, included 7,777 men with testicular cancer. A one-way ANOVA
      was used for significant differences among racial groups in age and stage of
      tumor at diagnosis. The main research variables were race, age at diagnosis, and
      tumor stage. Hispanic males were found to be diagnosed at the significantly
      youngest age (29.8 years old) and White males at the oldest age (35.0). Even with
      the oldest age at diagnosis, White males were diagnosed at the significantly
      lowest tumor stage (M = 2.3), which was highest for Black males (2.5). Minority
      males are diagnosed at the earliest age, yet their tumor stage is significantly
      higher than that for White males. Therefore nurses need to screen all males
      regardless of ethnicity for testicular cancer.

PMID- 16410438
TI  - The meaning of family caregiving in Japan and the United States: a qualitative
      comparative study.
AB  - This study explores how cultural values affect the meaning and experiences of
      daughter (or daughter-in-law) caregivers of elderly persons with dementia by
      comparing caregivers in the United States and Japan. Nine American and seven
      Japanese caregivers were interviewed twice at 6-month intervals. Interviews were
      audiotaped and analyzed using constant-comparative techniques. Data suggest that
      moral obligation to care and intense loss are two universal themes of caregiving.
      However the experiences and perceptions of the role of caregivers from these two
      cultures differed in select ways that were captured within three categories:
      reasons for caregiving, caregiving as a career, and caregiving as a life phase or
      detour. Findings suggest that American caregivers may need greater anticipatory
      socialization regarding the caregiving role, whereas Japanese caregivers may
      benefit from assistance in accepting needed services.

PMID- 16410439
TI  - Thai school-age children's perception of fear.
AB  - Information about how Thai school-age children perceive fear is necessary for the
      development of culturally appropriate anxiety or fear measures. The purpose of
      this study was to describe Thai school-age children's perceptions of fear from
      their own perspective. Qualitative data from 13 Thai students in Grades 3 to 6 in
      three schools in Bangkok were obtained by semistructured, formal interviews,
      combined with drawings. The data were analyzed using content analysis within the
      frame of category development in the grounded theory method. Several culturally
      specific aspects of fear were revealed. This information is useful for health
      care providers caring for Thai children. The results of this study also
      illustrate the importance of carefully assessing children from culturally diverse
      backgrounds related to manifestations of anxiety or fear.

PMID- 16410440
TI  - Cultural competence in nursing: new meanings.
AB  - Shortages of nurses challenge the provision of health care in developed countries
      including those in the European Union (EU), but there has been no upward trend in
      recruitment of nurses from EU countries with a surplus. A remedy is to facilitate
      migration of nurses around Europe. However, the importance of the concept of
      cultural competence has been overlooked within EU health care systems. Migrant
      nurses from EU countries employed in the United Kingdom indicate that they have
      experienced problems arising from a variety of issues related to cultural
      diversity. Countries such as the United Kingdom could benefit from introducing
      enculturation courses for migrant nurses.

PMID- 16410441
TI  - Community home-based care in a rural village: challenges and strategies.
AB  - In Botswana, there has been an increase in community home-based care (CHBC)
      following a shift from hospital care to CHBC because of the HIV/AIDS epidemic.
      Yet the health care system has limited resources. To fulfill one of the terms of
      reference of the World Health Organization Collaboration Centre at the Department
      of Nursing, University of Botswana, an outreach program was developed in
      collaboration with 18 lay volunteers in a nearby village, Mmopane. This article
      discusses the process of establishing the CHBC committee and the challenges faced
      by faculty, students, and lay caregivers in working with a diverse CHBC group to
      render culturally sensitive care. Strategies for dealing with these challenges
      are discussed.

PMID- 16410442
TI  - Severe pulmonary complications in Japanese patients after bortezomib treatment
      for refractory multiple myeloma.
AB  - Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity.
      Its frequent adverse effects are manageable, including gastrointestinal symptoms,
      peripheral neuropathy, and thrombocytopenia. Severe lung toxicity has not
      previously been reported. Between June 2004 and September 2005, 13 Japanese
      patients with multiple myeloma were treated with bortezomib in Toranomon
      Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four
      of them developed severe pulmonary complications, and 2 died of respiratory
      failure without progression of underlying disease. To our knowledge, this is the
      first report on life-threatening pulmonary adverse effects after bortezomib
      therapy. Previous clinical studies on bortezomib, mostly in the United States and
      Europe, have shown low incidences of pulmonary adverse effects. Our study
      suggests that bortezomib can cause serious lung injury, and that its incidence
      might vary among different ethnicities. Clinicians need to be alert to the
      possibility.

PMID- 16410443
TI  - Reconstitution of a functional human immune system in immunodeficient mice
      through combined human fetal thymus/liver and CD34+ cell transplantation.
AB  - Studies of the human immune system have been limited by the lack of an
      appropriate in vivo model. For this reason, efforts have been made to develop
      murine models with a functional human immune system. We report here that
      cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic
      stem/progenitor cells led to the development of sustained human hematopoiesis and
      a functional human immune system in immunodeficient NOD/SCID mice. The humanized
      mice showed systemic repopulation with a comprehensive array of human
      lymphohematopoietic cells, including T cells, B cells, and dendritic cells, and
      the formation of secondary lymphoid organs. Furthermore, these mice produce high
      levels of human IgM and IgG antibodies and mediate strong immune responses in
      vivo as demonstrated by skin xenograft rejection. Thus, the humanized NOD/SCID
      mice described in this paper provide a powerful model system to study human
      immune function.

PMID- 16410444
TI  - Regulatory dendritic cells act as regulators of acute lethal systemic
      inflammatory response.
AB  - Bacterial infection triggers host inflammation through the activation of immune
      cells, leading to the elimination of bacteria. However, the regulatory mechanisms
      of the host inflammatory response remain unknown. Here we report that a subset of
      potent tolerogenic dendritic cells (DCs), regulatory DCs (DC(regs)), control the
      systemic inflammatory response. Unlike normal DCs, which produced proinflammatory
      cytokines in response to bacterial lipopolysaccharide (LPS), DC(regs) produced
      fewer proinflammatory cytokines and instead preferentially produced interleukin
      10 (IL-10), and these events involved the expression of IkappaBNS and Bcl-3 as
      well as cyclic AMP (cAMP)-mediated activation of protein kinase A (PKA). In
      addition, DC(regs) not only suppressed LPS-induced production of proinflammatory
      cytokines in macrophages, but also reduced their serum levels in mice.
      Furthermore, DC(regs) protected mice against the lethality induced by
      experimental endotoxemia and bacterial peritonitis. The inhibitory effect of
      DC(regs) against inflammatory responses involved the production of IL-10. On the
      other hand, naturally existing tolerogenic DC subsets producing IL-10,
      CD11c(low)CD45RB(high) DCs, also suppressed LPS-induced host inflammatory
      responses. Thus, a subset of tolerogenic DCs act as potential regulators of the
      host inflammatory response, and they might have preventive and therapeutic
      potential for the treatment of systemic as well as local inflammatory diseases.

PMID- 16410445
TI  - In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in
      patients with multiple myeloma.
AB  - In solid tumors, leukemias, and lymphomas, increased frequencies of functional
      CD4+CD25(high) regulatory T cells (T(reg) cells) have been previously
      demonstrated. In healthy individuals, T(reg) cells consist not only of memory but
      also of naive T cells, which can undergo peripheral expansion and are
      characterized by a relative enrichment for autoreactive T-cell receptors. Here,
      we demonstrate in patients with premalignant monoclonal gammopathy of
      undetermined significance and patients with multiple myeloma that functional
      FoxP3(+) T(reg) cells of naive, central, and effector memory phenotype as
      determined by CCR7 and CD45RA expression are significantly expanded. Low
      frequencies of T-cell receptor excision circles in naive T(reg) cells in both
      healthy controls and multiple myeloma patients point to peripheral expansion as
      the prominent mechanism of increased frequencies of naive T(reg) cells in these
      cancer patients. These findings strongly suggest that the increase of functional
      T(reg) cells in cancer patients is a response to the process of malignant
      transformation.

PMID- 16410446
TI  - AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with
      risk-adapted intensive chemotherapy.
AB  - We aimed to compare AIDS risk-adapted intensive chemotherapy in AIDS-related
      lymphoma (ARL) patients before and after the advent of highly active
      antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years
      were randomly assigned to chemotherapy after stratification according to an HIV
      score based on performance status, prior AIDS, and CD4(+) cell counts below 0.10
      x 10(9)/L (100/mm(3)). A total of 218 good-risk patients (HIV score 0) received
      ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or
      CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177
      intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90
      poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The
      5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47%
      for CHOP (P = .85); in the intermediate-risk group, 28% for CHOP versus 24% for
      Ld-CHOP (P = .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS
      (P = .14). The time-dependent Cox model demonstrated that the only significant
      factors for OS were HAART (relative risk [RR] 1.6, P < .001), HIV score (RR 1.7,
      P < .001), and the International Prognostic Index (IPI) score (RR 1.5, P < .001)
      but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV
      score, IPI score, and HAART affect survival but not the intensity of the CHOP
      based chemotherapy.

PMID- 16410447
TI  - Photochemically treated fresh frozen plasma for transfusion of patients with
      acquired coagulopathy of liver disease.
AB  - An ex vivo photochemical treatment (PCT) process was developed to inactivate
      pathogens in fresh frozen plasma (PCT-FFP). A prospective, controlled, double
      blinded, randomized study was conducted to evaluate the efficacy and safety of
      PCT-FFP compared with conventional FFP (C-FFP). Patients (n = 121) with acquired
      coagulopathy, largely due to liver disease, including hepatic transplantation,
      were transfused with either PCT-FFP or C-FFP for up to 7 days. Primary end points
      were changes in the prothrombin time (PT) and the partial thromboplastin time
      (PTT) in response to the first FFP transfusion. Secondary analyses compared
      changes in the PT and the PTT, factor VII levels, clinical hemostasis, blood
      component usage, and safety following FFP transfusions for up to 7 days.
      Following the first transfusion, correction in the PT and PTT adjusted for FFP
      dose and patient weight was not different. Changes in the PT were equivalent
      between treatment groups (P = .002 by noninferiority). Equivalence was not
      demonstrated for changes in the PTT. Following multiple transfusions, correction
      of the PT and the PTT was similar between groups. No differences were observed in
      use of blood components, clinical hemostasis, or safety. These results suggest
      PCT-FFP supported hemostasis in the treatment of acquired coagulopathy similarly
      to conventional FFP.

PMID- 16410449
TI  - Point mutations in the juxtamembrane domain of FLT3 define a new class of
      activating mutations in AML.
AB  - In acute myeloid leukemia (AML), two clusters of activating mutations are known
      in the FMS-like tyrosine kinase-3 (FLT3) gene: FLT3-internal tandem duplications
      (FLT3-ITDs) in the juxtamembrane (JM) domain in 20% to 25% of patients, and FLT3
      point mutations in the tyrosine-kinase domain (FLT3-TKD) in 7% to 10% of
      patients, respectively. Here, we have characterized a new class of activating
      point mutations (PMs) that cluster in a 16-amino acid stretch of the
      juxtamembrane domain of FLT3 (FLT3-JM-PMs). Expression of 4 FLT3-JM-PMs in
      interleukin-3 (IL-3)-dependent Ba/F3 cells led to factor-independent growth,
      hyperresponsiveness to FLT3 ligand, and resistance to apoptotic cell death. FLT3
      JM-PM receptors were autophosphorylated and showed a higher constitutive
      dimerization rate compared with the FLT3-wild-type (WT) receptor. As a molecular
      mechanism, we could show activation of STAT5 and up-regulation of Bcl-x(L) by all
      FLT3-JM-PMs. The FLT3 inhibitor PKC412 abrogated the factor-independent growth of
      FLT3-JM-PM-expressing cells. Compared with FLT3-ITD and FLT3-TKD mutants, the
      FLT3-JM-PMs showed a weaker transforming potential related to lower
      autophosphorylation of the receptor and its downstream target STAT5. Mapping of
      the FLT3-JM-PMs on the crystal structure of FLT3 showed that these mutations
      reduce the stability of the autoinhibitory JM domain, and provides a structural
      basis for the transforming capacity of this new class of gain-of-function
      mutations of FLT3.

PMID- 16410448
TI  - Host factors that impact the biodistribution and persistence of multipotent adult
      progenitor cells.
AB  - Multipotent adult progenitor cells (MAPCs) are marrow-derived pluripotent stem
      cells with a broad differentiation potential. We sought to identify factors that
      affect adoptively transferred MAPCs. In vitro, MAPCs expressed low levels of
      major histocompatibility complex (MHC) antigens, failed to stimulate CD4(+) and
      CD8(+) T-cell alloresponses, and were targets of NK cytolysis. To study in vivo
      biodistribution, we labeled MAPCs with luciferase for sequential quantification
      of bioluminescence and DsRed2 for immunohistochemical analysis. C57BL /6 MAPCs
      were infused intravenously into C57BL /6, Rag-2(-/-) (T- and B-cell-deficient),
      and Rag-2(-/-)/IL-2Rgamma(c)(-/-) (T-, B-, and NK-cell-deficient) mice. In C57BL
      /6 mice, MAPCs were transiently detected only in the chest compared with long
      term persistence in T- and B-cell-deficient mice. NK depletion reduced MAPC
      elimination. Because the lungs were the major uptake site after intravenous
      injection, intra-arterial injections were tested and found to result in more
      widespread biodistribution. Widespread MAPC biodistribution and long-term
      persistence were seen in irradiated recipients given allogeneic marrow and MAPCs;
      such MAPCs expressed MHC class I antigens in tissues. Our data indicate that the
      biodistribution and persistence of reporter gene-labeled MAPCs are maximized
      after intra-arterial delivery or host irradiation and that T cells, B cells, and
      NK cells contribute to in vivo MAPC rejection.

PMID- 16410450
TI  - Implication of the folate-methionine metabolism pathways in susceptibility to
      follicular lymphomas.
AB  - The incidence of follicular lymphoma (FL) in industrialized countries has been
      increasing since the 1950s. Polymorphisms in genes encoding key enzymes
      controlling folate-methionine metabolism, including methylenetetrahydrofolate
      reductase (MTHFR), methionine synthase (MS or MTR), serine
      hydroxymethyltransferase (SHMT), and thymidylate synthase (TS or TYMS), modify
      the risk of various cancers and possibly FL. This study specifically looks for an
      association between MTHFR, MTR, TYMS, and SHMT polymorphisms and the risk of FL.
      We carried out a case-control study with 172 patients diagnosed with FL and 206
      control subjects. We report that the risk of FL was doubled by the association of
      one mutant allele at both MTHFR polymorphisms. Individuals with MTR 2756AA had 2
      fold higher risk of FL, and subjects not having at least one TYMS 2R allele
      showed a 2-fold higher risk of FL. The MTR 2756AA genotype conferred a greater
      multivariate-adjusted relative risk of FL, and the risk was multiplied by almost
      5 in the TYMS2R(-)/MTR 2756AA combination. In conclusion, common polymorphisms in
      key enzymes of the folate-methionine metabolism pathway result in an increased
      risk of FL and suggest that inadequate intake of dietary folate and other methyl
      donor nutrients may contribute to the development of this malignancy.

PMID- 16410451
TI  - Induction of the plasminogen activator inhibitor-2 in cells expressing the
      ZNF198/FGFR1 fusion kinase that is involved in atypical myeloproliferative
      disease.
AB  - The ZNF198/FGFR1 fusion kinase associated with an atypical myeloproliferative
      disease is constitutively activated and regulates several STAT transcription
      factors. We used oligonucleotide microarrays to compare the gene-expression
      profiles between HEK-293 cells that stably express either the ZNF198/FGFR1
      chimeric protein or the wild-type ZNF198 gene. Expression of the plasminogen
      activator inhibitor-2 (PAI-2/SERPINB2) was highly increased in cells expressing
      the fusion gene. Western blot analysis demonstrated that HEK-293 cells do not
      express PAI-2 endogenously, but in ZNF198/FGFR1-expressing cells 2 molecular
      forms of PAI-2, which were 47 kDa and 32 kDa, were expressed intracellularly, and
      a 60-kDa form was secreted. Similarly, expression of ZNF198/FGFR1 in BaF/3 mouse
      hematopoietic cells also induced the expression of the PAI-2 protein.
      Immunoprecipitation analysis revealed that both intracellular forms of PAI-2 bind
      to the ZNF198/FGFR1 kinase. Treatment of HEK-293 and BaF/3 cells with TNF-alpha
      in the presence of cycloheximide, induced apoptosis in both cases. In contrast,
      HEK-293 and BaF/3 cells expressing ZNF198/FGFR1 were resistant to TNF-alpha
      induced apoptosis. These observations suggest that expression of the ZNF198/FGFR1
      fusion gene is associated with specific PAI-2-mediated resistance to apoptosis
      which may contribute to the highly malignant nature of leukemic cells carrying
      this fusion kinase gene.

PMID- 16410452
TI  - A family with Papillon-Lefevre syndrome reveals a requirement for cathepsin C in
      granzyme B activation and NK cell cytolytic activity.
AB  - Activation of granzyme B, a key cytolytic effector molecule of natural killer
      (NK) cells, requires removal of an N-terminal pro-domain. In mice, cathepsin C is
      required for granzyme processing and normal NK cell cytolytic function, whereas
      in patients with Papillon-Lefevre syndrome (PLS), loss-of-function mutations in
      cathepsin C do not affect lymphokine activated killer (LAK) cell function. Here
      we demonstrate that resting PLS NK cells do have a cytolytic defect and fail to
      induce the caspase cascade in target cells. NK cells from these patients contain
      inactive granzyme B, indicating that cathepsin C is required for granzyme B
      activation in unstimulated human NK cells. However, in vitro activation of PLS NK
      cells with interleukin-2 restores cytolytic function and granzyme B activity by a
      cathepsin C-independent mechanism. This is the first documented example of a
      human mutation affecting granzyme B activity and highlights the importance of
      cathepsin C in human NK cell function.

PMID- 16410453
TI  - Update on treatment recommendations from the Third International Workshop on
      Waldenstrom's macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is a B-cell disorder characterized by the
      infiltration of lymphoplasmacytic cells into bone marrow and the presence of an
      IgM monoclonal gammopathy. As part of the Third International Workshop on WM,
      held October 7 to 10, 2004 in Paris, France, a consensus panel charged with
      providing treatment recommendations for WM updated its recommendations on both
      frontline and salvage therapies. The panel considered encouraging results from
      recent studies that addressed the use of extended-dose rituximab as well as other
      treatment options: therapy with either nucleoside analogs and alkylator agents,
      rituximab in combination with nucleoside analogs, nucleoside analogs plus
      alkylator agents, or combination chemotherapies, such as CHOP (cyclophosphamide,
      doxorubicin, vincristine, prednisone) or cyclophosphamide and dexamethasone. The
      panel determined that these were reasonable treatment options for WM patients and
      such therapeutic approaches were likely to yield results that are at least as
      good as if not better than the currently recommended use of single-agent
      alkylator, nucleoside analog, or standard-dose rituximab therapy. Such approaches
      were deemed to be reasonable treatment for WM patients in both the upfront and
      salvage settings, though randomized studies addressing the efficacy and toxicity
      of such novel approaches over previously established standard of care options are
      needed.

PMID- 16410454
TI  - Destabilizing role of cathepsin S in murine atherosclerotic plaques.
AB  - OBJECTIVE: Lysosomal proteinases have been implicated in a number of pathologies
      associated with extracellular matrix breakdown. Therefore, we investigated the
      possibility that the lysosomal proteinase cathepsin S may be involved in
      atherosclerotic plaque destabilization. METHODS AND RESULTS: Atherosclerotic
      plaques in the brachiocephalic arteries of fat-fed apolipoprotein E/cathepsin S
      double knockout mice had 73% fewer acute plaque ruptures (P=0.026) and were 46%
      smaller (P=0.025) than those in age-, strain-, and sex-matched apolipoprotein E
      single knockout controls. When the incidence of acute plaque rupture was
      normalized for plaque size, the reduction in the double knockouts was 72%
      (P=0.039). The number of buried fibrous layers, indicative of an unstable plaque
      phenotype, was reduced by 67% in the double knockouts (P=0.008). The cysteine
      proteinase inhibitor, egg white cystatin, was biotinylated and used as an active
      site-directed probe for cathepsins. Biotinylated cystatin selectively detected
      cathepsin S in extracts of human carotid atherosclerotic plaque. Active cathepsin
      S was detectable in extracts of human atherosclerotic plaque but not in
      nondiseased carotid arteries. Active cathepsins were especially prominent in
      macrophages in the shoulder regions of plaques, areas considered to be vulnerable
      to rupture. Cathepsin S protein colocalized with regions of elastin degradation
      in human coronary plaques. CONCLUSIONS: These data provide direct evidence that
      an endogenous proteinase, cathepsin S, plays an important role in atherosclerotic
      plaque destabilization and rupture.

PMID- 16410455
TI  - Oxidative stress and vascular disease: 2005 Duff lecture.
AB  - There is compelling evidence that oxidative stress plays a key role in the
      pathophysiology of several major cardiovascular diseases. In atherosclerosis,
      hypertension, stroke, diabetes, and heart failure, expression of superoxide is
      increased in blood vessels, and endothelial vasomotor function is impaired,
      presumably caused in large part by inactivation of nitric oxide by superoxide.
      Endothelial dysfunction is predictive of cardiovascular risk, and probably plays
      a key role in the pathophysiology of atherosclerosis and its complications. In
      preliminary studies in hypercholesterolemic mice and in older humans, we have
      found high levels of superoxide in the aortic valve, as well as aorta. We
      speculate that superoxide, in addition to playing a key role in atherogenesis,
      may play a key role in signaling that leads to calcific aortic valvular stenosis.
      Antioxidant enzymes, especially the three isoforms of superoxide dismutase (SOD),
      modulate basal levels of superoxide and protect against vasomotor dysfunction. A
      common gene variant of extracellular SOD (ecSOD) is associated with increased
      risk of ischemic heart disease. We have made recombinant adenoviruses to examine
      cardiovascular effects of ecSOD and its heparin-binding domain. This approach
      might be used to study the almost 500 other proteins with a heparin-binding
      domain. Finally, several key unanswered questions in relation to oxidative stress
      and atherosclerosis are raised, and proposed as fruitful areas of research.

PMID- 16410456
TI  - Apolipoproteins C-III and A-V as predictors of very-low-density lipoprotein
      triglyceride and apolipoprotein B-100 kinetics.
AB  - OBJECTIVE: We investigated the associations between plasma very-low-density
      lipoprotein (VLDL)-apolipoprotein (apo)C-III and apoA-V concentrations and the
      kinetics of VLDL-apoB-100 and VLDL triglycerides in 15 men. We also explored the
      relationship between these parameters of VLDL metabolism and VLDL-apoC-III
      kinetics. METHODS AND RESULTS: ApoC-III, apoB, and triglyceride kinetics in VLDL
      were determined using stable isotopes and multicompartmental modeling to estimate
      production rate (PR) and fractional catabolic rate (FCR). Plasma VLDL-apoC-III
      concentration was significantly and inversely associated with the FCRs of VLDL
      triglycerides (r=-0.610) and VLDL-apoB (r=-0.791), and positively correlated with
      the PR of VLDL-apoC-III (r=0.842). However, apoA-V concentration was not
      significantly associated with any of the kinetic variables. There was a
      significant association (P<0.01) between the PRs of VLDL triglycerides and VLDL
      apoB (r=0.641), and between the FCRs of VLDL triglycerides and VLDL-apoB
      (r=0.737). In multiple regression analysis, plasma VLDL-apoC-III concentration
      was a significant predictor of VLDL triglyceride FCR (beta-coefficient=-0.575)
      and VLDL-apoB FCR (beta-coefficient=-0.839). CONCLUSIONS: Our findings suggest
      that increased VLDL-apoC-III concentrations resulting from an overproduction of
      VLDL-apoC-III are strongly associated with the delayed catabolism of
      triglycerides and apoB in VLDL. We also demonstrated that the kinetics of VLDL
      triglycerides and apoB are closely coupled. Our data do not support a role for
      plasma apoA-V in regulating VLDL kinetics.

PMID- 16410457
TI  - Relative contributions of ABCA1 and SR-BI to cholesterol efflux to serum from
      fibroblasts and macrophages.
AB  - OBJECTIVE: Cholesterol efflux is achieved by several mechanisms. This study
      examines contributions of these pathways to efflux to human serum. METHODS AND
      RESULTS: Human fibroblasts were stably transfected with SR-BI while ABCA1 was
      upregulated. Quantitation of cholesterol efflux to human serum demonstrated that
      there was efflux from cells without either protein. Expression of ABCA1 produced
      a small increase in efflux, whereas SR-BI expression had a dramatic impact. To
      quantitate ABCA1 and SR-BI contribution, fibroblasts were pretreated with
      Probucol and BLT-1 to, respectively, inhibit these efflux proteins. Exposing SR
      BI-expressing fibroblasts to BLT-1 inhibited efflux by 67%. Probucol pretreatment
      of ABCA1-expressing fibroblasts reduced efflux to serum by 26%. A large fraction
      of total efflux was uninhibited. For both J774 and mouse peritoneal macrophages,
      contributions of either ABCA1 or SR-BI to efflux to serum were low, with
      background/uninhibited efflux contributing from 70% to 90% of total efflux.
      CONCLUSIONS: We have shown that ABCA1-mediated efflux to serum responds to the
      pool of lipid-free/poor apolipoproteins, whereas phospholipid-containing
      particles mediate SR-BI efflux. Although SR-BI and ABCA1 contribute to efflux
      from fibroblasts and cholesterol-enriched macrophages, a large proportion of the
      total efflux to human serum is mediated by a mechanism that is neither SR-BI nor
      ABCA1.

PMID- 16410458
TI  - Differential healing activities of CD34+ and CD14+ endothelial cell progenitors.
AB  - OBJECTIVE: Peripheral blood contains primitive (stem cell-like) and monocytic
      like endothelial cell progenitors. Diabetes apparently converts these primitive
      progenitors, from a pro-angiogenic to anti-angiogenic phenotype. Monocytic
      progenitors seem to be less affected by diabetes, but potential pro-angiogenic
      activities of freshly isolated monocytic progenitors remain unexplored. We
      compared the ability of primitive and monocytic endothelial cell progenitors to
      stimulate vascular growth and healing in diabetes and investigated potential
      molecular mechanisms through which the cells mediate their in vivo effects.
      METHODS AND RESULTS: Human CD34+ primitive progenitors and CD14+ monocytic
      progenitors were injected locally into the ischemic limbs of diabetic mice. CD14+
      cell therapy improved healing and vessel growth, although not as rapidly or
      effectively as CD34+ cell treatment. Western blot analysis revealed that cell
      therapy modulated expression of molecules in the VEGF, MCP-1, and angiopoietin
      pathways. CONCLUSIONS: Injection of freshly isolated circulating CD14+ cells
      improves healing and vascular growth indicating their potential for use in acute
      clinical settings. Importantly, CD14+ cells could provide a therapeutic option
      for people with diabetes, the function of whose CD34+ cells may be compromised.
      At least some progenitor-induced healing probably is mediated through increased
      sensitivity to VEGF and increases in MCP-1, and possibly modulation of
      angiopoietins.

PMID- 16410459
TI  - Lipoprotein lipase bound to apolipoprotein B lipoproteins accelerates clearance
      of postprandial lipoproteins in humans.
AB  - OBJECTIVE: Experiments in cells and animal models show that lipoprotein lipase
      (LpL) bound to apolipoprotein (apo)B lipoproteins enhances their uptake by
      receptor mediated pathways. It is unknown whether this pathway is important in
      humans. METHODS AND RESULTS: ApoB lipoproteins with LpL were isolated from normal
      subjects after oral fat loading by immunoaffinity chromatography and were further
      separated into apoB100 and apoB48 lipoproteins. Postprandially, apoB lipoproteins
      with LpL had significantly greater increases (4- to 10-fold) and faster rates of
      clearance (5- to 8-fold) percentage-wise than those without LpL. apoB
      lipoproteins with LpL had enhanced clearance regardless of whether they also
      contained apoE. LpL was particularly important for the clearance of apoB48
      lipoproteins, of which 25% (range, 11% to 31%) could be removed from circulation
      together with LpL during the postprandial state. apoB lipoproteins with LpL were
      larger in size and were enriched in triglyceride, cholesterol, and apoE compared
      with those without LpL. However, neither size nor apoE content explained the
      faster clearance rates of LpL-containing lipoproteins. CONCLUSIONS: Plasma LpL
      may act like an apolipoprotein to enhance the clearance of apoB lipoproteins in
      humans, a mechanism particularly important for intestinal lipoproteins in the
      postprandial state.

PMID- 16410460
TI  - Effect of rosiglitazone treatment on plaque inflammation and collagen content in
      nondiabetic patients: data from a randomized placebo-controlled trial.
AB  - BACKGROUND: Therapeutic strategies to stabilize advanced arteriosclerotic lesions
      may prevent plaque rupture and reduce the incidence of acute coronary syndromes.
      Thiazolidinediones (TZDs), like rosiglitazone, are oral antidiabetic drugs with
      additional antiinflammatory and potential antiatherogenic properties. In a
      randomized, placebo-controlled, single-blind trial, we examined the effect of 4
      weeks of rosiglitazone therapy on histomorphological characteristics of plaque
      stability in artery specimen of nondiabetic patients scheduled for elective
      carotid endarterectomy. METHODS AND RESULTS: A total of 24 nondiabetic patients
      with symptomatic carotid artery stenosis were randomly assigned to rosiglitazone
      (4 mg BID) or placebo in addition to standard therapy. In this population of
      nondiabetic patients, rosiglitazone treatment did not significantly change
      fasting blood glucose, fasting insulin, or lipid parameters. In contrast,
      rosiglitazone significantly reduced CD4-lymphocyte content as well as macrophage
      HLA-DR expression in the shoulder region, reflecting less inflammatory activation
      of these cells by lymphocyte interferon-gamma. Moreover, rosiglitazone
      significantly increased plaque collagen content (7.7+/-1.6% versus 3.7+/-0.7% of
      plaque area; P=0.036) compared with placebo, suggesting that TZD treatment may
      stabilize arteriosclerotic lesions. In addition, rosiglitazone reduced serum
      levels of 2 inflammatory arteriosclerosis markers: C-reactive protein and serum
      amyloid A. CONCLUSIONS: Four weeks of treatment with rosiglitazone significantly
      reduces vascular inflammation in nondiabetic patients, leading to a more stable
      type of arteriosclerotic lesion.

PMID- 16410461
TI  - Tetrapeptide AcSDKP induces postischemic neovascularization through monocyte
      chemoattractant protein-1 signaling.
AB  - BACKGROUND: We investigated the putative proangiogenic activity and molecular
      pathway(s) of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in a model of
      surgically induced hindlimb ischemia. METHODS AND RESULTS: Hindlimb ischemia was
      induced by femoral artery ligature and an osmotic minipump was implanted
      subcutaneously to deliver low (0.12 mg/kg per day) or high (1.2 mg/kg per day)
      doses of AcSDKP, for 7 or 21 days. Angiography scores, arteriole density,
      capillary number, and foot perfusion were increased at day 21 in the high-dose
      AcSDKP-treated mice (by 1.9-, 1.8-, 1.3-, and 1.6-fold, respectively) compared
      with control animals (P<0.05, P<0.01, P<0.01, respectively). AcSDKP treatment for
      24 hours upregulated the monocyte chemoattractant protein-1 (MCP-1) mRNA and
      protein levels by 1.5-fold in cultured endothelial cells (P<0.01). In the
      ischemic hindlimb model, administration of AcSDKP also enhanced MCP-1 mRNA levels
      by 90-fold in ischemic leg (P<0.001) and MCP-1 plasma levels by 3-fold (P<0.001
      versus untreated ischemic control mice). MCP-1 levels upregulation were
      associated with a 2.3-fold increase in the number of Mac3-positive cells in
      ischemic area of AcSDKP-treated mice (P<0.001 versus untreated animals).
      Interestingly, AcSDKP-induced monocyte/macrophage infiltration and postischemic
      neovascularization was fully blunted in MCP-1-deficient animals. CONCLUSIONS:
      AcSDKP stimulates postischemic neovascularization through activation of a
      proinflammatory MCP-1-related pathway.

PMID- 16410462
TI  - Leukocyte transglutaminase 2 expression limits atherosclerotic lesion size.
AB  - OBJECTIVE: Transglutaminase 2 (TG2), a broadly expressed regulator of protein
      cross-linking, wound healing, and tissue fibrosis, mediates apoptotic cell
      ingestion and transforming growth factor-beta release by macrophages and thereby
      can limit leukocyte-mediated inflammation. In atherosclerosis, oxidative stress
      and accumulation of unesterified cholesterol stimulate atherosclerotic lesion
      cell apoptosis. Cell death in advanced atherosclerotic lesions promotes lesion
      expansion and vulnerable plaques prone to rupture. Hence, we tested the
      hypothesis that leukocyte TG2 expression limits atherosclerosis. METHODS AND
      RESULTS: We transplanted TG2-/- or TG2+/+ bone marrow into lethally irradiated
      low-density lipoprotein receptor (LDLR)-/- mice and evaluated diet-induced
      atherosclerosis after 16 weeks. We subsequently studied cultured TG2-/- and
      congenic TG2+/+ mouse macrophages for selected atherogenesis regulatory
      functions. Atherosclerotic aortic valve lesions in LDLR-/- recipients of TG2-/-
      bone marrow were larger and more subintimal lesional macrophage penetration than
      in TG2+/+ marrow recipients. Lesion intimal TG2 expression appeared robust in
      TG2+/+ but not TG2-/- marrow recipients. Cultured TG2-/- macrophages demonstrated
      diminished phagocytosis of apoptotic leukocytes, unaltered endocytosis, and
      degradation of oxidized LDL but decreased retinoic acid induction of the reverse
      cholesterol transport and apoptotic cell uptake mediator ABCA1. CONCLUSIONS: We
      conclude that macrophage TG2 expression promotes both apoptotic cell clearance
      and ABCA1 expression in vitro and limits atherosclerotic lesion size in vivo.

PMID- 16410464
TI  - Advances in neurosonology 2005.

PMID- 16410463
TI  - Direct interaction of the cell division cycle 37 homolog inhibits endothelial
      nitric oxide synthase activity.
AB  - Endothelial NO synthase (eNOS) via the production of NO in the endothelium plays
      a key role in cardiovascular biology and is tightly regulated by co- and
      posttranslational mechanisms, phosphorylation, and protein-protein interactions.
      The cell division cycle 37 homolog (Cdc37) is a key heat shock protein 90 (Hsp90)
      cochaperone for protein kinase clients, and Akt/Hsp90 interaction is dependent on
      Cdc37. Because both Hsp90 and Akt are key eNOS regulatory proteins, we
      hypothesized that Cdc37 interacts with eNOS as part of the regulatory complex. In
      the present study, we demonstrate by coimmunoprecipitation and affinity
      purification in bovine aortic endothelial cells (BAECs) that Cdc37 is complexed
      with eNOS, Hsp90, and Akt. In addition, cell fractionation data indicate that
      Cdc37 is found in caveolae with eNOS. Further analysis by in vitro binding assays
      reveals a direct interaction between purified Cdc37 and eNOS. Incubation of
      purified Cdc37 with purified wild-type eNOS decreases eNOS activity in vitro.
      Overexpression of wild-type Cdc37 in BAECs inhibits eNOS activity and NO release,
      whereas overexpression of S13A-Cdc37 mutant in BAECs increases eNOS activity and
      NO release. Taken together, these data suggest that Cdc37 has a direct regulatory
      interaction with eNOS and may play an important role in mediating the eNOS
      protein complex formation as well as subsequent eNOS phosphorylation and
      activation.

PMID- 16410465
TI  - The dynamics of statins: from event prevention to neuroprotection.

PMID- 16410466
TI  - Advances in interventional neuroradiology 2005.

PMID- 16410467
TI  - Advances in imaging 2005.

PMID- 16410468
TI  - The harms and benefits of inflammatory and immune responses in vascular disease.

PMID- 16410469
TI  - Thrombolytics, anticoagulants, and antiplatelet agents.

PMID- 16410471
TI  - Advances in subarachnoid hemorrhage.

PMID- 16410472
TI  - Advances in vascular cognitive impairment 2005.

PMID- 16410473
TI  - Transient ischemic attacks: stratifying risk.

PMID- 16410474
TI  - Organized stroke care.

PMID- 16410475
TI  - Advances in primary stroke prevention.

PMID- 16410476
TI  - Brain recovery and rehabilitation.

PMID- 16410477
TI  - Update on genetics of stroke and cerebrovascular disease 2005.

PMID- 16410478
TI  - Advances in intracerebral hemorrhage management.

PMID- 16410479
TI  - Deliberate distal displacement of a middle cerebral artery embolus as an
      alternative method to treat a thrombolytic-resistant clot.

PMID- 16410481
TI  - Relationship between cerebral circulatory reserve and oxygen extraction fraction
      in patients with major cerebral artery occlusive disease: a positron emission
      tomography study.
AB  - BACKGROUND AND PURPOSE: The present study examined the relationship between
      circulatory and metabolic reserve in patients with hemodynamic impairment.
      METHODS: Positron emission tomography was used to investigate 40 patients with
      major cerebral artery occlusive disease. The ratio of cerebral blood volume to
      cerebral blood flow (CBV/CBF) and vasoreactivity in response to hypercapnia
      (%CBF(hypercapnia)) and acetazolamide (ACZ) stress (%CBF(ACZ)) were measured to
      evaluate circulatory reserve. Oxygen extraction fraction (OEF) was measured to
      evaluate metabolic reserve. To detect relationships between circulation reserve
      and OEF, cerebral hemispheres were grouped into 5 or 6 stepwise groups based on
      reduction of circulation reserve. RESULTS: OEF was significantly elevated in
      hemispheres with CBV/CBF > or =0.11 minutes and in hemispheres with
      %CBF(hypercapnia) <0%. OEF was significantly increased according to %CBF(ACZ) in
      hemispheres with %CBF(ACZ) <15% and plateaued at levels below -15%. CONCLUSIONS:
      Metabolic reserve consumption began at CBV/CBF > or =0.11 minutes,
      CBF(hypercapnia) <0%, and CBF(ACZ) <15%.

PMID- 16410482
TI  - A randomized controlled trial of supervised versus unsupervised exercise programs
      for ambulatory stroke survivors.
AB  - BACKGROUND AND PURPOSE: Little is known about the relative efficacy of supervised
      versus unsupervised community exercise programs for stroke survivors. This study
      compared the effectiveness of a 10-week supervised strengthening and conditioning
      program (supervised) with a 1-week supervised instruction program followed by a 9
      week unsupervised home program (unsupervised) and evaluated retention of changes
      at 6 months and 1 year after program completion. METHODS: Seventy-two subjects
      retained at baseline (27 women, 45 men; mean+/-SD age, 64.6+/-11.8 years) were
      randomly allocated to receive the supervised or unsupervised program. The primary
      outcome was walking speed over 6 minutes, and secondary outcome measures were
      Human Activity Profile, Medical Outcome Study 36-Item Short-Form survey (SF-36),
      Physiological Cost Index, and lower extremity muscle strength. RESULTS: The 6
      minute walking speed increased significantly in both groups and remained
      significantly improved by 1 year. The Human Activity Profile demonstrated an
      increasing trend only in the supervised group that was significant by 1 year. The
      SF-36 Physical Component summary score increased significantly in the supervised
      group and remained improved by 1 year; the unsupervised group showed significant
      improvement at 1 year. Women made greater gains in supervised programs, but men
      made greater gains in unsupervised programs. CONCLUSIONS: Supervised exercise
      programs and unsupervised programs after initial supervised instruction were both
      associated with physical benefits that were retained for 1 year, although
      supervised programs showed trends to greater improvements in self-reported gains.
      Gender differences require further research.

PMID- 16410483
TI  - Are there patients with acute ischemic stroke and atrial fibrillation that
      benefit from low molecular weight heparin?
AB  - BACKGROUND AND PURPOSE: Treatment doses of heparins are not recommended for acute
      ischemic stroke. Despite this, their use in this setting is widespread. We
      investigated whether subgroups of patients with acute ischemic stroke and atrial
      fibrillation, identified by clinical, hemostatic (d-dimer, prothombin
      fragments(1+2) [F(1+2)], soluble fibrin monomer), or inflammatory (C-reactive
      protein [CRP]) variables might have a differential response to low molecular
      weight heparin (LMWH) over aspirin. In addition, we sought to identify factors
      associated with a poor clinical outcome at 3 months. METHODS: We conducted a post
      hoc subgroup analysis of a randomized, placebo-controlled, double-blind trial
      (Heparin in Acute Embolic Stroke Trial) designed to test the hypothesis that
      treatment doses of LMWH (dalteparin; 100 IU/kg BID) would be superior to aspirin
      (160 mg per day) in patients with acute ischemic stroke and atrial fibrillation.
      For the current analysis, 431 participants were included. The primary outcome
      measure was a poor outcome at 3 months, defined as death or dependency in
      activities of daily living. Using regression analysis, we determined whether any
      of the chosen variables were associated with a differential response to
      dalteparin (treatment interaction) or with poor outcome. RESULTS: In the
      multivariable logistic regression model, none of the clinical, hemostatic, or
      inflammatory variables were associated with a significant treatment interaction.
      Stroke severity (odds ratio [OR], 1.09 [95% CI, 1.07 to 1.12]), increasing age
      (OR, 1.09 [CI, 1.05 to 1.14]), CRP level (OR, 1.32 [CI, 1.04 to 1.66]), and
      F(1+2) level (OR, 1.77 [CI, 1.07 to 2.91]) were independently associated with a
      poor outcome at 3 months. CONCLUSIONS: Our study does not support the use of
      treatment doses of LMWH in any of the studied subgroups of patients with acute
      ischemic stroke and atrial fibrillation. Age, stroke severity, CRP, and F(1+2)
      were predictive of poor outcome at 3 months.

PMID- 16410485
TI  - Editorial retraction.

PMID- 16410484
TI  - Compartment volume influences microtubule dynamic instability: a model study.
AB  - Microtubules (MTs) are cytoskeletal polymers that exhibit dynamic instability,
      the random alternation between growth and shrinkage. MT dynamic instability plays
      an essential role in cell development, division, and motility. To investigate
      dynamic instability, simulation models have been widely used. However, conditions
      under which the concentration of free tubulin fluctuates as a result of growing
      or shrinking MTs have not been studied before. Such conditions can arise, for
      example, in small compartments, such as neuronal growth cones. Here we
      investigate by means of computational modeling how concentration fluctuations
      caused by growing and shrinking MTs affect dynamic instability. We show that
      these fluctuations shorten MT growth and shrinkage times and change their
      distributions from exponential to non-exponential, gamma-like. Gamma-like
      distributions of MT growth and shrinkage times, which allow optimal stochastic
      searching by MTs, have been observed in various cell types and are believed to
      require structural changes in the MT during growth or shrinkage. Our results,
      however, show that these distributions can already arise as a result of
      fluctuations in the concentration of free tubulin due to growing and shrinking
      MTs. Such fluctuations are possible not only in small compartments but also when
      tubulin diffusion is slow or when many MTs (de)polymerize synchronously. Volume
      and all other factors that influence these fluctuations can affect MT dynamic
      instability and, consequently, the processes that depend on it, such as neuronal
      growth cone behavior and cell motility in general.

PMID- 16410486
TI  - A radio pulsar spinning at 716 Hz.
AB  - We have discovered a 716-hertz eclipsing binary radio pulsar in the globular
      cluster Terzan 5 using the Green Bank Telescope. It is the fastest spinning
      neutron star found to date, breaking the 24-year record held by the 642-hertz
      pulsar B1937+21. The difficulty in detecting this pulsar, because of its very low
      flux density and high eclipse fraction (approximately 40% of the orbit), suggests
      that even faster spinning neutron stars exist. If the pulsar has a mass less than
      twice the mass of the Sun, then its radius must be constrained by the spin rate
      to be <16 kilometers. The short period of this pulsar also constrains models that
      suggest that gravitational radiation, through an r-mode (Rossby wave)
      instability, limits the maximum spin frequency of neutron stars.

PMID- 16410487
TI  - Optical signatures of coupled quantum dots.
AB  - An asymmetric pair of coupled InAs quantum dots is tuned into resonance by
      applying an electric field so that a single hole forms a coherent molecular wave
      function. The optical spectrum shows a rich pattern of level anticrossings and
      crossings that can be understood as a superposition of charge and spin
      configurations of the two dots. Coulomb interactions shift the molecular
      resonance of the optically excited state (charged exciton) with respect to the
      ground state (single charge), enabling light-induced coupling of the quantum
      dots. This result demonstrates the possibility of optically coupling quantum dots
      for application in quantum information processing.

PMID- 16410489
TI  - Good news--and bad.

PMID- 16410488
TI  - New neurons follow the flow of cerebrospinal fluid in the adult brain.
AB  - In the adult brain, neuroblasts born in the subventricular zone migrate from the
      walls of the lateral ventricles to the olfactory bulb. How do these cells orient
      over such a long distance and through complex territories? Here we show that
      neuroblast migration parallels cerebrospinal fluid (CSF) flow. Beating of
      ependymal cilia is required for normal CSF flow, concentration gradient formation
      of CSF guidance molecules, and directional migration of neuroblasts. Results
      suggest that polarized epithelial cells contribute important vectorial
      information for guidance of young, migrating neurons.

PMID- 16410491
TI  - Nuclear weapons. Iran's trouble with molybdenum may give diplomacy a second
      chance.

PMID- 16410490
TI  - Cloning. South Korean team's remaining human stem cell claim demolished.

PMID- 16410493
TI  - Research facilities. Scripps's offshoot stalled in south Florida.

PMID- 16410492
TI  - Botany. Plants may be hidden methane source.

PMID- 16410494
TI  - Regulatory science. More details sought in assessing health risks.

PMID- 16410495
TI  - Avian influenza. More cases in Turkey, but no mutations found.

PMID- 16410496
TI  - Global health. The new world of global health.

PMID- 16410497
TI  - Global health. Public-private partnerships proliferate.

PMID- 16410498
TI  - Research management. U.S. rules on accounting for grants amount to more than a
      hill of beans.

PMID- 16410499
TI  - Nuclear proliferation. A career change possible for North Korea's nuclear
      scientists?

PMID- 16410500
TI  - Planetary science. Long trek to solar system's last frontier begins.

PMID- 16410505
TI  - HIV research and access to treatment.

PMID- 16410506
TI  - Continuing progress in neuroinformatics.

PMID- 16410507
TI  - Loss of grants hurts the vulnerable.

PMID- 16410508
TI  - Comment on "Iron isotope constraints on the Archean and Paleoproterozoic ocean
      redox state".
AB  - Rouxel et al. (Reports, 18 February 2005, p. 1088) argued that changes in the
      iron isotopic composition of sedimentary sulfides reflect changes in the
      oxidation state of the atmosphere-ocean system between 2.3 and 1.8 million years
      ago. We show that misinterpretations of the origins of these minerals undermine
      their conclusions.

PMID- 16410509
TI  - Public health. Clinical trials results databases: unanswered questions.

PMID- 16410510
TI  - Structural biology. Two geometric solutions to a transporting problem.

PMID- 16410511
TI  - Applied physics. Where have all the transistors gone?

PMID- 16410513
TI  - Planetary science. Titan's zoo of clouds.

PMID- 16410512
TI  - Physiology. Running a clock requires quality time together.

PMID- 16410514
TI  - Systems biology. When proteomes collide.

PMID- 16410515
TI  - Plasmonics: merging photonics and electronics at nanoscale dimensions.
AB  - Electronic circuits provide us with the ability to control the transport and
      storage of electrons. However, the performance of electronic circuits is now
      becoming rather limited when digital information needs to be sent from one point
      to another. Photonics offers an effective solution to this problem by
      implementing optical communication systems based on optical fibers and photonic
      circuits. Unfortunately, the micrometer-scale bulky components of photonics have
      limited the integration of these components into electronic chips, which are now
      measured in nanometers. Surface plasmon-based circuits, which merge electronics
      and photonics at the nanoscale, may offer a solution to this size-compatibility
      problem. Here we review the current status and future prospects of plasmonics in
      various applications including plasmonic chips, light generation, and
      nanolithography.

PMID- 16410516
TI  - Interferometric coupling of the Keck telescopes with single-mode fibers.
AB  - Here we report successful interferometric coupling of two large telescopes with
      single-mode fibers. Interference fringes were obtained in the 2- to 2.3
      micrometer wavelength range on the star 107 Herculis by using the two Keck 10
      meter telescopes, each feeding their common interferometric focus with 300 meters
      of single-mode fibers. This experiment demonstrates the potential of fibers for
      future kilometric arrays of telescopes and is the first step toward the 'OHANA
      (Optical Hawaiian Array for Nanoradian Astronomy) interferometer at the Mauna Kea
      observatory in Hawaii. It opens the way to sensitive optical imagers with
      resolutions below 1 milli-arc second. Our experimental setup can be directly
      extended to large telescopes separated by many hundreds of meters.

PMID- 16410517
TI  - Structural basis for double-stranded RNA processing by Dicer.
AB  - The specialized ribonuclease Dicer initiates RNA interference by cleaving double
      stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides in
      length. In the crystal structure of an intact Dicer enzyme, the PAZ domain, a
      module that binds the end of dsRNA, is separated from the two catalytic
      ribonuclease III (RNase III) domains by a flat, positively charged surface. The
      65 angstrom distance between the PAZ and RNase III domains matches the length
      spanned by 25 base pairs of RNA. Thus, Dicer itself is a molecular ruler that
      recognizes dsRNA and cleaves a specified distance from the helical end.

PMID- 16410518
TI  - The nature of the 660-kilometer discontinuity in Earth's mantle from global
      seismic observations of PP precursors.
AB  - The 660-kilometer discontinuity, which separates Earth's upper and lower mantle,
      has been detected routinely on a global scale in underside reflections of
      precursors to SS shear waves. Here, we report observations of this discontinuity
      in many different regions, using precursors to compressional PP waves. The
      apparent absence of such precursors in previous studies had posed major problems
      for models of mantle composition. We find a complicated structure, showing single
      and double reflections ranging in depth from 640 to 720 kilometers, that requires
      the existence of multiple phase transitions at the base of the transition zone.
      The results are consistent with a pyrolite mantle composition.

PMID- 16410519
TI  - The latitudinal distribution of clouds on Titan.
AB  - Clouds have been observed recently on Titan, through the thick haze, using near
      infrared spectroscopy and images near the south pole and in temperate regions
      near 40 degrees S. Recent telescope and Cassini orbiter observations are now
      providing an insight into cloud climatology. To study clouds, we have developed a
      general circulation model of Titan that includes cloud microphysics. We identify
      and explain the formation of several types of ethane and methane clouds,
      including south polar clouds and sporadic clouds in temperate regions and
      especially at 40 degrees in the summer hemisphere. The locations, frequencies,
      and composition of these cloud types are essentially explained by the large-scale
      circulation.

PMID- 16410520
TI  - Majority logic gate for magnetic quantum-dot cellular automata.
AB  - We describe the operation of, and demonstrate logic functionality in, networks of
      physically coupled, nanometer-scale magnets designed for digital computation in
      magnetic quantum-dot cellular automata (MQCA) systems. MQCA offer low power
      dissipation and high integration density of functional elements and operate at
      room temperature. The basic MQCA logic gate, that is, the three-input majority
      logic gate, is demonstrated.

PMID- 16410521
TI  - Grain boundary strengthening in alumina by rare earth impurities.
AB  - Impurity doping often alters or improves the properties of materials. In alumina,
      grain boundaries play a key role in deformation mechanisms, particularly in the
      phenomenon of grain boundary sliding during creep at high temperatures. We
      elucidated the atomic-scale structure in alumina grain boundaries and its
      relationship to the suppression of creep upon doping with yttrium by using atomic
      resolution microscopy and high-precision calculations. We find that the yttrium
      segregates to very localized regions along the grain boundary and alters the
      local bonding environment, thereby strengthening the boundary against mechanical
      creep.

PMID- 16410522
TI  - Ion distributions near a liquid-liquid interface.
AB  - Mean field theories of ion distributions, such as the Gouy-Chapman theory that
      describes the distribution near a charged planar surface, ignore the molecular
      scale structure in the liquid solution. The predictions of the Gouy-Chapman
      theory vary substantially from our x-ray reflectivity measurements of the
      interface between two electrolyte solutions. Molecular dynamics simulations,
      which include the liquid structure, were used to calculate the potential of mean
      force on a single ion. We used this potential of mean force in a generalized
      Poisson-Boltzmann equation to predict the full ion distributions. These
      distributions agree with our measurements without any adjustable parameters.

PMID- 16410523
TI  - PER-TIM interactions in living Drosophila cells: an interval timer for the
      circadian clock.
AB  - In contrast to current models, fluorescence resonance energy transfer
      measurements using a single-cell imaging assay with fluorescent forms of PER and
      TIM showed that these proteins bind rapidly and persist in the cytoplasm while
      gradually accumulating in discrete foci. After approximately 6 hours, complexes
      abruptly dissociated, as PER and TIM independently moved to the nucleus in a
      narrow time frame. The per(L) mutation delayed nuclear accumulation in vivo and
      in our cultured cell system, but without affecting rates of PER/TIM assembly or
      dissociation. This finding points to a previously unrecognized form of temporal
      regulation that underlies the periodicity of the circadian clock.

PMID- 16410524
TI  - Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits.
AB  - Axons in the cerebral cortex receive synaptic input at the axon initial segment
      almost exclusively from gamma-aminobutyric acid-releasing (GABAergic) axo-axonic
      cells (AACs). The axon has the lowest threshold for action potential generation
      in neurons; thus, AACs are considered to be strategically placed inhibitory
      neurons controlling neuronal output. However, we found that AACs can depolarize
      pyramidal cells and can initiate stereotyped series of synaptic events in rat and
      human cortical networks because of a depolarized reversal potential for axonal
      relative to perisomatic GABAergic inputs. Excitation and signal propagation
      initiated by AACs is supported by the absence of the potassium chloride
      cotransporter 2 in the axon.

PMID- 16410525
TI  - Long-term transmission of defective RNA viruses in humans and Aedes mosquitoes.
AB  - In 2001, dengue virus type 1 (DENV-1) populations in humans and mosquitoes from
      Myanmar acquired a stop-codon mutation in the surface envelope (E) protein gene.
      Within a year, this stop-codon strain had spread to all individuals sampled. The
      presence of truncated E protein species within individual viral populations,
      along with a general relaxation in selective constraint, indicated that the stop
      codon strain represents a defective lineage of DENV-1. We propose that such long
      term transmission of defective RNA viruses in nature was achieved through
      complementation by coinfection of host cells with functional viruses.

PMID- 16410526
TI  - Radiculopathy associated with disc herniation.

PMID- 16410527
TI  - Responsiveness of the shoulder function assessment scale in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To investigate the responsiveness of the Shoulder Function Assessment
      scale (SFA) in patients with rheumatoid arthritis (RA). METHODS: In 35 patients
      with RA receiving a (peri-)articular injection because of local shoulder
      complaints the SFA, impact of shoulder function on activities of daily living,
      active shoulder range of motion (ROM), the 28 joint count Disease Activity Score
      (DAS28), and the Health Assessment Questionnaire (HAQ) were measured before and 4
      6 weeks after treatment. Responsiveness was determined using the standardised
      response mean (SRM), effect size (ES), and responsiveness ratio (RR). RESULTS:
      Overall, significant improvement was seen according to the SFA (mean change 10.9
      (95% confidence interval 6.5 to 15.3)), active shoulder ROM (except external
      rotation), and the impact of shoulder function on daily activities. In addition,
      the DAS28 and HAQ scores improved significantly. The responsiveness of the SFA
      was excellent, with the SRM, ES, and RR being -0.86, -1.16, and 1.28,
      respectively. CONCLUSIONS: In addition to its good validity and reliability, the
      SFA proved to have a high sensitivity to clinical changes in patients with RA who
      received local treatment for shoulder complaints.

PMID- 16410528
TI  - Clinical characteristics of patients with myositis and autoantibodies to
      different fragments of the Mi-2 beta antigen.
AB  - OBJECTIVES: To assess the clinical implications of autoantibodies directed
      against different parts of the Mi-2 beta autoantigen in patients with myositis.
      METHODS: A systematic assessment of the clinical, laboratory, and histological
      characteristics of 48 anti-Mi-2 positive patients from six European centres was
      made. Anti-Mi-2 autoantibodies were determined with an ELISA using four
      overlapping fragments spanning the entire amino acid sequence of the autoantigen.
      Data were compared with results for a large group of anti-Mi-2 negative patients
      with myositis published previously. RESULTS: Anti-Mi-2 autoantibodies were found
      in dermatomyositis, polymyositis, and inclusion body myositis. In general,
      myositis with anti-Mi-2 autoantibodies was characterised by relatively mild
      disease, sometimes accompanied by extra-muscular symptoms, including arthralgia,
      arthritis, Raynaud's phenomenon, and interstitial lung disease. Cardiac disease
      was not seen, and treatment response was fair. No differences were found between
      patients with autoantibodies to different fragments of the Mi-2 beta antigen,
      except for a potentially increased risk of cancer in patients with antibodies
      directed to the N-terminal fragment of the autoantigen. CONCLUSIONS: Anti-Mi-2
      autoantibodies are not a marker of a specific subtype of myositis. No significant
      differences between patients with autoantibodies to different fragments of the Mi
      2 beta autoantigen are found, with the possible exception of an increased risk of
      cancer in patients with antibodies to the N-terminal fragment.

PMID- 16410530
TI  - Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of
      patients with neuropsychiatric lupus.
AB  - BACKGROUND: An imbalance in cytokine homoeostasis is thought to have a key role
      in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and
      recently, a role for chemokines has been noted. OBJECTIVE: To compare
      concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal
      fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms.
      METHODS: CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89
      patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP
      1/CCL2 concentrations were measured with an ELISA. RESULTS: The average
      concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non
      NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly
      higher in the NPSLE group than in the non-NPSLE group (p<0.001). In one
      representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in
      parallel with a decline in neuropsychiatric symptoms. CONCLUSIONS: CSF MCP-1/CCL2
      levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2
      may have an important role in the expression of NPSLE. These results indicate
      that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting
      that it might be used as a diagnostic tool and a monitor for therapeutic
      responses in patients with NPSLE.

PMID- 16410529
TI  - Effects of corticosteroids and immunosuppressors on idiopathic inflammatory
      myopathy related myocarditis evaluated by magnetic resonance imaging.
AB  - BACKGROUND: Cardiac involvement in idiopathic inflammatory myopathy has been
      recognised as an important prognostic factor, but treatment remains empirical.
      OBJECTIVE: To investigate the effects of corticosteroids and immunosuppressors on
      myocarditis in patients with inflammatory myopathies. METHODS: Patients with
      inflammatory myositis of recent onset who had not received treatment were
      evaluated for associated myocarditis by magnetic resonance imaging (MRI) and
      reinvestigated after treatment with high dose corticosteroids and
      immunosuppressors. RESULTS: Four patients with histologically proven myositis
      were included. Two patients with polymyositis had cardiac clinical symptoms. Two
      other patients with dermatomyositis and diffuse cutaneous systemic sclerosis
      polymyositis overlap syndrome were asymptomatic. In three cases the usual
      conventional screening tests were normal. For all patients an area of contrast
      enhancement and hypokinesia detected by cardiac MRI was markedly reduced after
      treatment with corticosteroids and immunosuppressors for 6 months. CONCLUSION:
      Treatment with intravenous methylprednisolone followed by prednisone and
      immunosuppressive therapy seems to be effective for treating myocardial
      involvement in patients with idiopathic inflammatory myopathies, either alone or
      presenting as overlap syndromes. Cardiovascular MRI is a non-invasive technique
      that may be a powerful tool for diagnosis and monitoring of myocardial
      inflammation in this setting.

PMID- 16410532
TI  - Colour duplex sonography of finger arteries in vasculitis and in systemic
      sclerosis.
AB  - CASE REPORTS: Three patients-two with Wegener's granulomatosis and one with an
      overlap syndrome of rheumatoid vasculitis, systemic lupus erythematosus, and
      antiphospholipid syndrome-are described. All patients experienced a sudden onset
      of Raynaud's phenomenon or acrocyanosis when they had a flare of their disease.
      DISCUSSION: Ultrasonography (US) showed dark (hypoechoic) arteries without colour
      signals, resembling the US pattern of embolism. In contrast, US in patients with
      systemic sclerosis is entirely different, delineating a smaller artery lumen,
      reduced pulsation, and thickened, slightly hyperechoic artery walls.

PMID- 16410533
TI  - Multiple haematological malignancies in a patient with rheumatoid arthritis
      without exposure to disease modifying therapy.

PMID- 16410531
TI  - Differential regulation of the bone morphogenic protein antagonist chordin in
      human normal and osteoarthritic chondrocytes.
AB  - OBJECTIVE: To investigate the distribution of the bone morphogenic protein (BMP)
      antagonist chordin in normal and osteoarthritic cartilage and synovial membranes,
      and its regulation in chondrocytes and synovial fibroblasts by inflammatory and
      growth factors. METHODS: Localisation of chordin in tissues was undertaken by
      immunohistochemistry and gene regulation was determined by real time polymerase
      chain reaction. RESULTS: In normal cartilage, chordin was found at low levels
      (mean (SD), 7.6 (1.3)%), mainly in the very superficial layers. In
      osteoarthritis, chordin was also found in the superficial layers (8.9 (1.1)%),
      though at a significantly higher level (24.7 (1.5)%) in the last two thirds of
      the cartilage. In contrast to normal cells, chordin mRNA and protein levels were
      significantly downregulated (p<0.01) in osteoarthritic chondrocytes by all the
      growth factors tested. Interferon gamma stimulated chordin expression in normal
      but not in osteoarthritic chondrocytes (p<0.0002), while interleukin 1 beta and
      tumour necrosis factor alpha did not affect the expression level. However, no
      difference was found in either the distribution or regulation of chordin in
      normal and osteoarthritic synovial membranes or synovial fibroblasts.
      CONCLUSIONS: The differential distribution and regulation of chordin in normal
      and osteoarthritic cartilage and chondrocytes suggests an involvement of this
      antagonist in the osteoarthritic process.

PMID- 16410534
TI  - Altered peptide ligands regulate muscarinic acetylcholine receptor reactive T
      cells of patients with Sjogren's syndrome.

PMID- 16410535
TI  - IL1RN genotype as a risk factor for joint pain in hereditary haemochromatosis?

PMID- 16410536
TI  - Human parvovirus B19 viraemia is associated with neither IgM positivity nor
      anaemia in patients with rheumatic diseases.

PMID- 16410537
TI  - Absence of epicardial coronary stenosis in patients with systemic sclerosis with
      severe impairment of coronary flow reserve.

PMID- 16410538
TI  - Safety and patient satisfaction of infliximab administration in an extramural
      setting supervised by a rheumatology specialist nurse.

PMID- 16410539
TI  - Collapsing glomerulopathy in systemic autoimmune disorders: a case occurring in
      the course of full blown systemic lupus erythematosus.

PMID- 16410540
TI  - Lack of association of mannose binding lectin variant alleles with systemic lupus
      erythematosus.

PMID- 16410541
TI  - Decreased levels of serum soluble HLA class I antigens in HLA-B27 positive
      spondyloarthropathies.

PMID- 16410542
TI  - Identification of transcriptional targets during pancreatic growth after partial
      pancreatectomy and exendin-4 treatment.
AB  - After partial pancreatectomy (Ppx), substantial regeneration of the endocrine and
      exocrine pancreatic compartments has been shown in adult rodents. Exendin-4 (Ex
      4) is a glucagon-like peptide-1 receptor agonist that augments endocrine beta
      cell mass by stimulating neogenesis, proliferation, and cell survival. After Ppx,
      treatment with Ex-4 ameliorates hyperglycemia by stimulating beta-cell mass
      recovery. We utilized a cDNA microarray approach to identify genes differentially
      regulated during pancreatic regeneration after Ppx and/or Ex-4 administration.
      The pancreatic remnant after Ppx showed a large number of differentially
      regulated genes. In contrast, Ex-4 treatment resulted in a smaller number of
      differentially regulated genes. Of note, a common subset of genes regulated by Ex
      4 and after Ppx was identified, including three members of the mitogenic Reg gene
      family, Reg2, -3gamma, and -3beta, as well as fragilis, a gene that maintains
      pluripotency during germ cell specification, and Serpin b1a, a member of an
      intracellular protease inhibitor family involved in cell survival. These
      observations were confirmed by real-time PCR. We determined that Reg3beta protein
      is also induced in the acinar pancreas after Ppx, suggesting a novel role for
      this factor in pancreatic growth or response to injury. Finally, comparison of
      transcription factor-binding sites present in the proximal promoters of these
      genes identified potential common transcription factors that may regulate these
      genes. Chromatin immunoprecipitation analyses confirmed Reg3gamma as a novel
      transcriptional target of Foxa2 (HNF3beta). Our data suggest molecular pathways
      that may regulate pancreatic growth and offer a unique set of candidate genes to
      target in the development of therapies aimed at improving pancreatic growth and
      function.

PMID- 16410543
TI  - Anatomical phenotyping in the brain and skull of a mutant mouse by magnetic
      resonance imaging and computed tomography.
AB  - Since genetically modified mice have become more common in biomedical research as
      models of human disease, a need has also grown for efficient and quantitative
      methods to assess mouse phenotype. One powerful means of phenotyping is
      characterization of anatomy in mutant vs. normal populations. Anatomical
      phenotyping requires visualization of structures in situ, quantification of
      complex shape differences between mouse populations, and detection of subtle or
      diffuse abnormalities during high-throughput survey work. These aims can be
      achieved with imaging techniques adapted from clinical radiology, such as
      magnetic resonance imaging and computed tomography. These imaging technologies
      provide an excellent nondestructive method for visualization of anatomy in live
      individuals or specimens. The computer-based analysis of these images then allows
      thorough anatomical characterizations. We present an automated method for
      analyzing multiple-image data sets. This method uses image registration to
      identify corresponding anatomy between control and mutant groups. Within- and
      between-group shape differences are used to map regions of significantly
      differing anatomy. These regions are highlighted and represented quantitatively
      by displacements and volume changes. This methodology is demonstrated for a
      partially characterized mouse mutation generated by N-ethyl-N-nitrosourea
      mutagenesis that is a putative model of the human syndrome oculodentodigital
      dysplasia, caused by point mutations in the gene encoding connexin 43.

PMID- 16410544
TI  - Noninvasive indirect imaging of vascular endothelial growth factor gene
      expression using bioluminescence imaging in living transgenic mice.
AB  - Vascular endothelial growth factor (VEGF) plays a critical role in the early
      activation of stromal tissues during wound healing and tumor growth. We report
      the use of a two-step transcriptional amplification (TSTA) approach to augment
      the transcriptional activity of the relatively weak VEGF promoter (pVEGF) using
      firefly luciferase (fl) reporter gene and bioluminescence imaging (BLI). In cell
      culture, we demonstrate that TSTA-based fl gene expression can be significantly
      enhanced over the direct one-step system. Using a transgenic mouse model (pVEGF
      TSTA-fl), we demonstrate the induction of VEGF gene expression using a wound
      healing model and a subcutaneous mammary tumor model. In skin-wounding
      experiments, pVEGF-induced fl expression in the wound lesion is detected on days
      4 and 5 and peaks on days 15-22. Furthermore, the bioluminescence signal shows
      good correlation with the endogenous VEGF protein levels in the wound tissue (r2
      = 0.70). In the mammary tumor model, fl expression is detected on day 3, peaks at
      day 17, and declines thereafter. These results support the use of noninvasive BLI
      for the longitudinal monitoring of VEGF induction during wound healing and tumor
      progression, and this mouse model should find use in various applications in
      which it is important to noninvasively study VEGF gene expression.

PMID- 16410545
TI  - Dystroglycan: from biosynthesis to pathogenesis of human disease.
AB  - Alpha- and beta-dystroglycan constitute a membrane-spanning complex that connects
      the extracellular matrix to the cytoskeleton. Although a structural role for
      dystroglycan had been identified, biochemical and genetic discoveries have
      recently highlighted the significance of posttranslational processing for
      dystroglycan function. Glycosylation is the crucial modification that modulates
      the function of dystroglycan as a receptor for extracellular binding partners. It
      has become clear that perturbation of dystroglycan glycosylation is the central
      event in the pathogenesis of several complex disorders, and recent advances
      suggest that glycosylation could be modulated to ameliorate the pathological
      features. Our increased understanding of the mechanisms of interaction of
      dystroglycan with its ligands has become an essential tool in deciphering the
      biological processes related to the human diseases in which the proteins are
      implicated.

PMID- 16410546
TI  - Of Myc and Mnt.
AB  - Deregulation of Myc expression is a common feature in cancer and leads to tumor
      formation in experimental model systems. There are several potential barriers
      that Myc must overcome in order to promote tumorigenesis, including its
      propensity to sensitize many cell types to apoptotic cell death. Myc activities
      appear also to be constrained and fine-tuned by a set of proteins that include
      the Mxd (formerly named Mad) family and the related protein Mnt. Like Myc-family
      proteins, Mxd and Mnt proteins use Max as a cofactor for DNA binding. But Mnt-Max
      and Mxd-Max complexes are transcriptional repressors and can antagonize the
      transcriptional activation function of Myc-Max. Studies examining the
      relationship between Myc, Mxd and Mnt proteins suggest that whereas Mnt plays a
      general role as a Myc antagonist, Mxd proteins have more specialized roles as Myc
      antagonist that is probably related to their more restricted expression patterns.
      The interplay between these proteins is postulated to fine-tune Myc activity for
      cell-cycle entry and exit, proliferation rate and apoptosis.

PMID- 16410547
TI  - PAIR2 is essential for homologous chromosome synapsis in rice meiosis I.
AB  - The PAIR2 gene is required for homologous chromosome synapsis at meiosis I in
      rice (Oryza sativa L.) and encodes a HORMA-domain protein that is homologous to
      Saccharomyces cerevisiae HOP1 and Arabidopsis ASY1. Immunocytological and
      electron microscopic analyses indicate that PAIR2 proteins associate with axial
      elements (AEs) at leptotene and zygotene, and is removed from the AEs of arm
      regions when homologous chromosomes have been synapsed. Immunocytology against a
      centromeric histone H3 variant revealed that PAIR2 remains at centromeres until
      diakinesis, by which time the homologous centromeres had already been synapsed.
      However, neither precocious segregation of sister chromatids nor kinetochore
      dysfunction is observed, and AEs are normally assembled in the mutant. In the
      pair2-null mutant, homologous chromosome synapsis is completely eliminated. This
      study provides the first description of AE-associated protein in monocot plants
      and indicates that PAIR2 plays an essential role in promoting homologous
      chromosome synapsis. However, PAIR2 does not play a role in AE formation, sister
      chromatid cohesion at centromeres or kinetochore assembly in meiosis I of rice.

PMID- 16410548
TI  - NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an
      acidic store in the secretory granule area.
AB  - Inositol trisphosphate and cyclic ADP-ribose release Ca2+ from the endoplasmic
      reticulum via inositol trisphosphate and ryanodine receptors, respectively. By
      contrast, nicotinic acid adenine dinucleotide phosphate may activate a novel Ca2+
      channel in an acid compartment. We show, in two-photon permeabilized pancreatic
      acinar cells, that the three messengers tested could each release Ca2+ from the
      endoplasmic reticulum and also from an acid store in the granular region. The
      nicotinic acid adenine dinucleotide phosphate action on both types of store, like
      that of cyclic ADP-ribose but unlike inositol trisphosphate, depended on
      operational ryanodine receptors, since it was blocked by ryanodine or ruthenium
      red. The acid Ca2+ store in the granular region did not have Golgi or lysosomal
      characteristics and might therefore be associated with the secretory granules.
      The endoplasmic reticulum is predominantly basal, but thin extensions penetrate
      into the granular area and cytosolic Ca2+ signals probably initiate at sites
      where endoplasmic reticulum elements and granules come close together.

PMID- 16410549
TI  - Nuclear titin interacts with A- and B-type lamins in vitro and in vivo.
AB  - Lamins form structural filaments in the nucleus. Mutations in A-type lamins cause
      muscular dystrophy, cardiomyopathy and other diseases, including progeroid
      syndromes. To identify new binding partners for lamin A, we carried out a two
      hybrid screen with a human skeletal-muscle cDNA library, using the Ig-fold domain
      of lamin A as bait. The C-terminal region of titin was recovered twice. Previous
      investigators showed that nuclear isoforms of titin are essential for chromosome
      condensation during mitosis. Our titin fragment, which includes two regions
      unique to titin (M-is6 and M-is7), bound directly to both A- and B-type lamins in
      vitro. Titin binding to disease-causing lamin A mutants R527P and R482Q was
      reduced 50%. Studies in living cells suggested lamin-titin interactions were
      physiologically relevant. In Caenorhabditis elegans embryos, two independent C.
      elegans (Ce)-titin antibodies colocalized with Ce-lamin at the nuclear envelope.
      In lamin-downregulated [lmn-1(RNAi)] embryos, Ce-titin was undetectable at the
      nuclear envelope suggesting its localization or stability requires Ce-lamin. In
      human cells (HeLa), antibodies against the titin-specific domain M-is6 gave both
      diffuse and punctate intranuclear staining by indirect immunofluorescence, and
      recognized at least three bands larger than 1 MDa in immunoblots of isolated HeLa
      nuclei. In HeLa cells that transiently overexpressed a lamin-binding fragment of
      titin, nuclei became grossly misshapen and herniated at sites lacking lamin B. We
      conclude that the C-terminus of nuclear titin binds lamins in vivo and might
      contribute to nuclear organization during interphase.

PMID- 16410550
TI  - A molecular link A molecular link between Hairless and Pros26.4, a member of the
      AAA-ATPase subunits of the proteasome 19S regulatory particle in Drosophila.
AB  - The proteasome is the major degradation machinery of the cell that regulates
      multiple cellular processes as diverse as cell cycle, signal transduction and
      gene expression. Recognition and unfolding of target proteins involves the
      regulatory cap whose base contains six AAA-ATPases that display reverse chaperone
      activity. One of them, Rpt2 (also known as S4), has an essential role in gating
      the degradative central core. We have isolated the orthologous gene Pros26.4 from
      Drosophila melanogaster as a molecular interaction partner of Hairless. Hairless
      plays a major role as antagonist of Notch signalling in Drosophila, prompting our
      interest in the Hairless-Pros26.4 interaction. We find that Pros26.4 negatively
      regulates Hairless at the genetic and molecular level. Depletion of Pros26.4 by
      using tissue-specific RNA interference (RNAi) resulted in a specific
      stabilization of the Hairless protein, but not in stabilization of the
      intracellular domain of Notch or the effector protein Suppressor of Hairless.
      Thus, the Hairless-Pros26.4 interaction provides a novel mechanism of positive
      regulation of Notch signalling.

PMID- 16410551
TI  - Nitric oxide mediates neurodegeneration and breakdown of the blood-brain barrier
      in tPA-dependent excitotoxic injury in mice.
AB  - Stroke and many neurodegenerative diseases culminate in neuronal death through a
      mechanism known as excitotoxicity. Excitotoxicity proceeds through a complex
      signaling pathway that includes the participation of the serine protease tissue
      plasminogen activator (tPA). tPA mediates neurotoxic effects on resident central
      nervous system cells as well alters blood-brain barrier (BBB) permeability, which
      further promotes neurodegeneration. Another signaling molecule that promotes
      neurodegeneration and BBB dysfunction is nitric oxide (NO), although its precise
      role in pathological progression remains unclear. We examine here the potentially
      interrelated roles of tPA, NO and peroxynitrite (ONOO-), which is the toxic
      metabolite of NO, in BBB breakdown and neurodegeneration following
      intrahippocampal injection of the glutamate analog kainite (KA). We find that NO
      and ONOO- production are linked to tPA-mediated excitotoxic injury, and
      demonstrate that NO provision suffices to restore the toxic effects of KA in tPA
      deficient mice that are normally resistant to excitotoxicity. NO also promotes
      BBB breakdown and excitotoxicity. Interestingly, BBB breakdown in itself does not
      suffice to elicit neurodegeneration; a subsequent ONOO(-)-mediated event is
      required. In conclusion, NO and ONOO- function as downstream effectors of tPA
      mediated excitotoxicity.

PMID- 16410553
TI  - Quality control of a mutant plasma membrane ATPase: ubiquitylation prevents cell
      surface stability.
AB  - The plasma membrane ATPase, Pma1, has remarkable longevity at the cell surface.
      In contrast to the wild-type protein, the temperature-sensitive mutant Pma1-10 is
      misfolded and undergoes rapid removal from the cell surface for vacuolar
      degradation. At the restrictive temperature, Pma1-10 becomes ubiquitylated before
      or upon arrival at the plasma membrane. Internalization from the plasma membrane
      and vacuolar degradation of Pma1-10 is dependent on the ubiquitin-interacting
      motif (UIM) of the epsin Ent1, suggesting recognition of ubiquitylated substrate
      by the endocytic machinery. Surprisingly, ubiquitylation of Pma1-10 is reversed
      when its internalization is blocked in an end3 mutant. Under these conditions,
      Pma1-10 acquires association with detergent-insoluble, glycolipid-enriched
      complexes (DIGs) which has been suggested to promote stability of wild-type Pma1.
      Ubiquitylation does not cause DIG exclusion because a Pma1-Ub fusion protein is
      not significantly excluded from DIGs. We suggest that ubiquitylation of Pma1-10
      represents a component of a quality control mechanism that targets the misfolded
      protein for removal from the plasma membrane. Rapid internalization of Pma1-10
      caused by its ubiquitylation may preempt establishment of stabilizing
      interactions.

PMID- 16410552
TI  - Trafficking from CD63-positive late endocytic multivesicular bodies is essential
      for intracellular development of Chlamydia trachomatis.
AB  - Chlamydiae are obligate intracellular bacterial pathogens that replicate solely
      within the confines of a membrane-bound vacuole termed an inclusion. Within this
      protected organelle, chlamydiae acquire host-cell-derived biosynthetic precursors
      necessary for intracellular subsistence, yet the mechanisms and pathways
      responsible for this acquisition remain elusive. The present study identifies an
      interaction between the chlamydial inclusion and multivesicular bodies, complex
      organelles pivotal in protein and lipid transport that are positioned along the
      endosome-lysosome pathway, and intersect the exocytic pathway in various cell
      types. Resident protein and lipid constituents of multivesicular bodies
      colocalized with intracellular chlamydiae, with direct delivery of the resident
      protein CD63 to the chlamydial inclusion. Interruption of trafficking from
      multivesicular bodies by pharmacological inhibitors and exogenous antibodies
      subsequently disrupted sphingolipid delivery to the maturing chlamydial inclusion
      and intracellular bacterial growth. This study identifies a trafficking pathway
      from CD63-positive multivesicular bodies to the bacterial inclusion, a novel
      interaction that provides essential lipids necessary for maintenance of a
      productive intracellular infection.

PMID- 16410554
TI  - The Shwachman-Bodian-Diamond syndrome gene encodes an RNA-binding protein that
      localizes to the pseudopod of Dictyostelium amoebae during chemotaxis.
AB  - The Shwachman-Bodian-Diamond syndrome (SBDS) is an autosomal disorder with
      multisystem defects. The Shwachman-Bodian-Diamond syndrome gene (SBDS), which
      contains mutations in a majority of SBDS patients, encodes a protein of unknown
      function, although it has been strongly implicated in RNA metabolism. There is
      also some evidence that it interacts with molecules that regulate cytoskeletal
      organization. Recently, it has been demonstrated by computer-assisted methods
      that the single behavioral defect of polymorphonuclear leukocytes (PMNs) of SBDS
      patients is the incapacity to orient correctly in a spatial gradient of
      chemoattractant. We considered using the social amoeba Dictyostelium discoideum,
      a model for PMN chemotaxis, an excellent system for elucidating the function of
      the SBDS protein. We first identified the homolog of SBDS in D. discoideum and
      found that the amino acids that are altered in human disease were conserved.
      Given that several proteins involved in chemotactic orientation localize to the
      pseudopods of cells undergoing chemotaxis, we tested whether the SBDS gene
      product did the same. We produced an SBDS-GFP chimeric in-frame fusion gene, and
      generated transformants either with multiple ectopic insertions of the fusion
      gene or multiple copies of a non-integrated plasmid carrying the fusion gene. In
      both cases, the SBDS-GFP protein was dispersed equally through the cytoplasm and
      pseudopods of cells migrating in buffer. However, we observed differential
      enrichment of SBDS in the pseudopods of cells treated with the chemoattractant
      cAMP, suggesting that the SBDS protein may play a role in chemotaxis. In light of
      these results, we discuss how SBDS might function during chemotaxis.

PMID- 16410555
TI  - Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate
      fibroblast growth factor receptor signaling.
AB  - Fibroblast growth factor receptor (FGFR) signaling is transduced by the mitogen
      activated protein kinase (MAPK) cascade and the signal transducers and activators
      of transcription (STATs). Suppressors of cytokine signaling (SOCS) proteins are
      expressed in response to cytokine-inducible stimulation of STAT phosphorylation,
      acting in a negative-feedback mechanism to hinder the activities of these
      receptors. However, there are no data concerning the role of SOCS proteins in the
      regulation of fibroblast growth factor receptor (FGFR) signaling. In the present
      study, we show that activation of FGFR in chondrocytes induces the expression of
      SOCS1 and SOCS3 mRNA, and that these proteins are constitutively associated with
      FGFR3, as demonstrated by co-immunoprecipitation studies. Transfection of cells
      with FGFR3-GFP and SOCS1-CFP revealed their colocalization, clustered prominently
      in the perinuclear cytosolic part of the cell. The effect of the interaction
      between FGFR3 and SOCS1 on receptor activity was investigated in a chondrocytic
      cell line overexpressing SOCS1. In these cells, STAT1 phosphorylation is
      repressed, MAPK phosphorylation is elevated and prolonged, and FGFR3
      downregulation is attenuated. Expression of osteopontin (OPN), which is directly
      upregulated by FGF in chondrocytes, was stimulated by lower levels of FGF in
      cells expressing SOCS1 compared with parental cells. Blocking of MAPK
      phosphorylation by PD98059 decreased OPN expression in both cell types, but this
      decrease was more marked in cells expressing SOCS1. The presented results suggest
      a novel interaction between the SOCS1 and SOCS3 proteins and the FGFR3 signaling
      pathway.

PMID- 16410556
TI  - When to test women for human papillomavirus.

PMID- 16410557
TI  - Primary care for refugees and asylum seekers.

PMID- 16410558
TI  - Cerebral palsy and perinatal exposure to neurotropic viruses.

PMID- 16410559
TI  - Introducing new health interventions.

PMID- 16410562
TI  - Children in Turkey die after contracting avian flu.

PMID- 16410560
TI  - Lymphogranuloma venereum.

PMID- 16410564
TI  - UK drug companies must disclose funding of patients' groups.

PMID- 16410565
TI  - Doctors outraged at Patriot Act's potential to seize medical records.

PMID- 16410580
TI  - Rains fail to bring relief in Zimbabwe.

PMID- 16410581
TI  - Report on E coli outbreak recommends review of guidance.

PMID- 16410582
TI  - Gastro-oesophageal reflux disease.

PMID- 16410583
TI  - Urinary tract infections in women: diagnosis and management in primary care.

PMID- 16410585
TI  - Ulcerative proctitis in men who have sex with men: an emerging outbreak.

PMID- 16410586
TI  - Medical treatment of early breast cancer. II: endocrine therapy.

PMID- 16410589
TI  - Waiting for radiotherapy.

PMID- 16410590
TI  - Evaluating and implementing new services.

PMID- 16410591
TI  - Adoption of new surgical technology.

PMID- 16410592
TI  - Project: London--supporting vulnerable populations.

PMID- 16410593
TI  - Mental health legislation and decision making capacity: autonomy in Alzheimer's
      disease is ignored and neglected.

PMID- 16410594
TI  - Deficiencies in rehabilitation after traumatic brain injury.

PMID- 16410595
TI  - Good quality monitoring is crucial for informed choice.

PMID- 16410596
TI  - HIV/AIDS is still a double sentence in prisons.

PMID- 16410597
TI  - Mental health legislation and decision making capacity: capacity is of more than
      practical benefit.

PMID- 16410598
TI  - Mental health legislation and decision making capacity: capacity is more complex
      than it looks.

PMID- 16410599
TI  - How Islam changed medicine: Al-Nafis, Servetus, and Colombo.

PMID- 16410600
TI  - How Islam changed medicine: Ibn Sina (Avicenna) saw medicine and surgery as one.

PMID- 16410601
TI  - How Islam changed medicine: Ibn al-Haytham and optics.

PMID- 16410602
TI  - UK experience of smoke-free young offenders institute.

PMID- 16410603
TI  - Disappearing teaspoons: spoon solutions.

PMID- 16410604
TI  - Disappearing teaspoons: teaspoons may reappear.

PMID- 16410605
TI  - Disappearing teaspoons: method of spoon surveillance was not adequate.

PMID- 16410607
TI  - Disappearing teaspoons: French data indicate global phenomenon.

PMID- 16410606
TI  - Disappearing teaspoons: teabags and forks are confounding factors.

PMID- 16410608
TI  - Career barriers perceived by hard-of-hearing adolescents: implications for
      practice from a mixed-methods study.
AB  - This study incorporated both quantitative and qualitative methods to examine the
      perception of career barriers by hard-of-hearing high school students being
      educated in regular classes with itinerant teacher support. Sixty-five students
      in Years 10, 11, and 12 completed a questionnaire about potential general and
      hearing-related barriers, and 12 of these respondents were subsequently
      interviewed. Findings indicated that other people's lack of understanding of
      their hearing loss constituted the greatest potential barrier to adolescents'
      educational and career goals. Students anticipated several other barriers in the
      form of functional hearing-related difficulties. Most students showed little
      awareness of helpful strategies or job accommodations and some had prematurely
      foreclosed on career choices. Implications for practice are outlined, and
      recommendations for teachers and career counselors are made.

PMID- 16410609
TI  - Joint attention strategies used by a preschool educator who is deaf.
AB  - This exploratory study examined the attention-gaining and attention-regaining
      strategies used by a preschool educator who is Deaf during child-directed play.
      Four children (2 with typical hearing and 2 with severe-to-profound hearing loss)
      were videotaped interacting with the educator in two different play contexts. The
      educator used four different strategies to gain and to regain the children's
      attention: visual, visual using an American Sign Language (ASL) sign,
      tactile/vibratory, and observing/waiting. Overall, tactile and visual strategies
      were used with the same frequency and occurred more often than either waiting or
      using an ASL sign to establish joint attention. With the exception of waiting,
      all strategies were equally successful at gaining or regaining the children's
      attention. The knowledge and experience of educators with hearing loss
      potentially provide important insights into enhancing the effectiveness of the
      communicative environment for preschool children with hearing loss. The
      implications of this line of inquiry include training for educators on the
      effective use of strategies to establish joint attention with preschool children
      with hearing loss.

PMID- 16410610
TI  - Speech reading and learning to read: a comparison of 8-year-old profoundly deaf
      children with good and poor reading ability.
AB  - Nine children with severe-profound prelingual hearing loss and single-word
      reading scores not more than 10 months behind chronological age (Good Readers)
      were matched with 9 children whose reading lag was at least 15 months (Poor
      Readers). Good Readers had significantly higher spelling and reading
      comprehension scores. They produced significantly more phonetic errors
      (indicating the use of phonological coding) and more often correctly represented
      the number of syllables in spelling than Poor Readers. They also scored more
      highly on orthographic awareness and were better at speech reading. Speech
      intelligibility was the same in the two groups. Cluster analysis revealed that
      only three Good Readers showed strong evidence of phonetic coding in spelling
      although seven had good representation of syllables; only four had high
      orthographic awareness scores. However, all 9 children were good speech readers,
      suggesting that a phonological code derived through speech reading may underpin
      reading success for deaf children.

PMID- 16410611
TI  - Cockayne syndrome group B protein has novel strand annealing and exchange
      activities.
AB  - Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized
      by UV sensitivity, severe neurological abnormalities and prageroid symptoms. The
      CS complementation group B (CSB) protein is involved in UV-induced transcription
      coupled repair (TCR), base excision repair and general transcription. CSB also
      has a DNA-dependent ATPase activity that may play a role in remodeling chromatin
      in vivo. This study reports the novel finding that CSB catalyzes the annealing of
      complementary single-stranded DNA (ssDNA) molecules with high efficiency, and has
      strand exchange activity. The rate of CSB-catalyzed annealing of complementary
      ssDNA is 25-fold faster than the rate of spontaneous ssDNA annealing under
      identical in vitro conditions and the reaction occurs with a high specificity in
      the presence of excess non-homologous ssDNA. The specificity and intrinsic nature
      of the reaction is also confirmed by the observation that it is stimulated by
      dephosphorylation of CSB, which occurs after UV-induced DNA damage, and is
      inhibited in the presence of ATPgammaS. Potential roles of CSB in cooperation
      with strand annealing and exchange activities for TCR and homologous
      recombination are discussed.

PMID- 16410612
TI  - Insights into the kinetics of siRNA-mediated gene silencing from live-cell and
      live-animal bioluminescent imaging.
AB  - Small interfering RNA (siRNA) molecules are potent effectors of post
      transcriptional gene silencing. Using noninvasive bioluminescent imaging and a
      mathematical model of siRNA delivery and function, the effects of target-specific
      and treatment-specific parameters on siRNA-mediated gene silencing are monitored
      in cells stably expressing the firefly luciferase protein. In vitro, luciferase
      protein levels recover to pre-treatment values within <1 week in rapidly dividing
      cell lines, but take longer than 3 weeks to return to steady-state levels in
      nondividing fibroblasts. Similar results are observed in vivo, with knockdown
      lasting approximately 10 days in subcutaneous tumors in A/J mice and 3-4 weeks in
      the nondividing hepatocytes of BALB/c mice. These data indicate that dilution due
      to cell division, and not intracellular siRNA half-life, governs the duration of
      gene silencing under these conditions. To demonstrate the practical use of the
      model in treatment design, model calculations are used to predict the dosing
      schedule required to maintain persistent silencing of target proteins with
      different half-lives in rapidly dividing or nondividing cells. The approach of
      bioluminescent imaging combined with mathematical modeling provides useful
      insights into siRNA function and may help expedite the translation of siRNA into
      clinically relevant therapeutics for disease treatment and management.

PMID- 16410613
TI  - Stabilities of HIV-1 DIS type RNA loop-loop interactions in vitro and in vivo.
AB  - RNA loop-loop interactions are a prevalent motif in the formation of tertiary
      structure and are well suited to trigger molecular recognition between RNA
      molecules. We determined the stabilities of several loop-loop interactions with a
      constant 6 bp core sequence and varying unpaired flanking nucleotides and found
      that the flanking bases have a strong influence on the stability and ion
      dependence of the kissing complex. In general, the stabilities determined in 1 M
      Na+ are equivalent to those in the presence of near physiological Mg2+
      concentrations. Therefore we further tested whether the stabilities determined in
      vitro and within yeast cells correlate, using a recently developed yeast RNA
      hybrid system. For the majority of the loop types analyzed here, the melting
      temperatures determined in vitro are in good agreement with the relative beta
      galactosidase activity in yeast cells, showing that data derived from in vitro
      measurements reflect in vivo properties. The most stable interactions are the
      naturally occurring HIV-1 DIS MAL and LAI derived loops with the motif (5'
      A(A)/(G)N6A 3'), emphasizing the crucial role of stable kissing complexes in HIV
      genome dimerization.

PMID- 16410614
TI  - A new NMR solution structure of the SL1 HIV-1Lai loop-loop dimer.
AB  - Dimerization of genomic RNA is directly related with the event of encapsidation
      and maturation of the virion. The initiating sequence of the dimerization is a
      short autocomplementary region in the hairpin loop SL1. We describe here a new
      solution structure of the RNA dimerization initiation site (DIS) of HIV-1(Lai).
      NMR pulsed field-gradient spin-echo techniques and multidimensional heteronuclear
      NMR spectroscopy indicate that this structure is formed by two hairpins linked by
      six Watson-Crick GC base pairs. Hinges between the stems and the loops are
      stabilized by intra and intermolecular interactions involving the A8, A9 and A16
      adenines. The coaxial alignment of the three A-type helices present in the
      structure is supported by previous crystallography analysis but the A8 and A9
      adenines are found in a bulged in position. These data suggest the existence of
      an equilibrium between bulged in and bulged out conformations in solution.

PMID- 16410615
TI  - The hepatitis B virus PRE contains a splicing regulatory element.
AB  - The posttranscriptional regulatory element (PRE) is considered to enhance
      hepatitis B virus (HBV) gene expression by facilitating the nuclear export of
      intronless viral subgenomic RNAs. Its role in the RNA metabolism of the viral
      pregenomic RNA (pgRNA) is currently unknown. We identified a positively cis
      acting splicing regulatory element (SRE-1) and present two lines of evidence for
      its functionality. Firstly, in a heterologous context SRE-1 functionally
      substitutes for a retroviral bidirectional exonic splicing enhancer (ESE). As
      expected, SRE-1 is a splicing enhancer also in its natural viral sequence
      context, since deletion of SRE-1 reduces splicing of pgRNA in cell culture
      experiments. Secondly, we show that stimulation of HBV RNA splicing by the
      splicing factor PSF was repressed by the PRE. Analysis of a variety of PSF
      mutants indicated that RNA-binding and protein-protein interaction were required
      to enhance splicing. In addition, we show that the PRE contributed to pgRNA
      stability, but has little influence on its nuclear export. Herein, we report for
      the first time that the PRE harbors splicing stimulating and inhibiting
      regulatory elements controlling processing of the viral pregenome. We discuss a
      model in which the regulation of pgRNA splicing depends on cellular factors
      interacting with the PRE.

PMID- 16410616
TI  - TACC3 mediates the association of MBD2 with histone acetyltransferases and
      relieves transcriptional repression of methylated promoters.
AB  - We have recently reported that a novel MBD2 interactor (MBDin) has the capacity
      to reactivate transcription from MBD2-repressed methylated promoters even in the
      absence of demethylation events. Here we show that another unrelated protein,
      TACC3, displays a similar activity on methylated genes. In addition the data
      reported here provide possible molecular mechanisms for the observed phenomenon.
      Immunoprecipitation experiments showed that MBD2/TACC3 form a complex in vivo
      with the histone acetyltransferase pCAF. MBD2 could also associate with HDAC2, a
      component of MeCP1 repression complex. However, we found that the complexes
      formed by MBD2 with TACC3/pCAF and with HDAC2 were mutually exclusive. Moreover,
      HAT enzymatic assays demonstrated that HAT activity associates with MBD2 in vivo
      and that such association significantly increased when TACC3 was over-expressed.
      Overall our findings suggest that TACC3 can be recruited by MBD2 on methylated
      promoters and is able to reactivate transcription possibly by favoring the
      formation of an HAT-containing MBD2 complex and, thus, switching the repression
      potential of MBD2 in activation even prior to eventual demethylation.

PMID- 16410619
TI  - Using clinical research.

PMID- 16410617
TI  - Characterization of sequences and mechanisms through which ISE/ISS-3 regulates
      FGFR2 splicing.
AB  - Alternative splicing of fibroblast growth factor receptor-2 (FGFR2) mutually
      exclusive exons IIIb and IIIc results in highly cell-type-specific expression of
      functionally distinct receptors, FGFR2-IIIb and FGFR2-IIIc. We previously
      identified an RNA cis-element, ISE/ISS-3, that enhanced exon IIIb splicing and
      silenced exon IIIc splicing. Here, we have performed comprehensive mutational
      analysis to define critical sequence motifs within this element that
      independently either enhance splicing of upstream exons or repress splicing of
      downstream exons. Such analysis included use of a novel fluorescence-based
      splicing reporter assay that allowed quantitative determination of relative
      functional activity of ISE/ISS-3 mutants using flow cytometric analysis of live
      cells. We determined that specific sequences within this element that mediate
      splicing enhancement also mediate splicing repression, depending on their
      position relative to a regulated exon. Thus, factors that bind the element are
      likely to be coordinately involved in mediating both aspects of splicing
      regulation. Exon IIIc silencing is dependent upon a suboptimal branchpoint
      sequence containing a guanine branchpoint nucleotide. Previous studies of exon
      IIIc splicing in HeLa nuclear extracts demonstrated that this guanine branchsite
      primarily impaired the second step of splicing suggesting that ISE/ISS-3 may
      block exon IIIc inclusion at this step. However, results presented here that
      include use of newly developed in vitro splicing assays of FGFR2 using extracts
      from a cell line expressing FGFR2-IIIb strongly suggest that cell-type-specific
      silencing of exon IIIc occurs at or prior to the first step of splicing.

PMID- 16410618
TI  - Translation of chloroplast psbD mRNA in Chlamydomonas is controlled by a
      secondary RNA structure blocking the AUG start codon.
AB  - Translation initiation represents a key step during regulation of gene expression
      in chloroplasts. Here, we report on the identification and characterization of
      three suppressor point mutations which overcome a translational defect caused by
      the deletion of a U-rich element in the 5'-untranslated region (5'-UTR) of the
      psbD mRNA in the green alga Chlamydomonas reinhardtii. All three suppressors
      affect a secondary RNA structure encompassing the psbD AUG initiation codon
      within a double-stranded region as judged by the analysis of site-directed
      chloroplast mutants as well as in vitro RNA mapping experiments using RNase H. In
      conclusion, the data suggest that these new element serves as a negative
      regulator which mediates a rapid shut-down of D2 synthesis.

PMID- 16410620
TI  - Health care workers' hand decontamination practices: an Irish study.
AB  - The primary purpose of this quasi-experimental research is to observe health care
      workers' compliance with hand-hygiene guidelines during patient care in an
      intensive care unit in Ireland before (pretest) and after (posttest)
      implementation of a multifaceted hand-hygiene program. Health care workers'
      attitudes, beliefs, and knowledge in relation to compliance with handwashing
      guidelines were also investigated. A convenience sample of nurses, doctors,
      physiotherapists, and care assistants (n = 73 observational participants, n = 62
      questionnaire respondents) was used. Data (N = 314 observations, 62
      questionnaires) were analyzed descriptively and cross-tabulated using chi-square
      (Pearson's) and Mann-Whitney statistical tests. Results revealed that a
      significant shift (32%) occurred in health care workers' compliance with
      handwashing guidelines (pretest 51%, posttest 83%, p < .001) following the
      interventional hand-hygiene program. Significant changes were also found in
      relation to health care workers' attitudes, beliefs, and knowledge (p < .05).

PMID- 16410622
TI  - Prevalence and symptoms of delirium superimposed on dementia.
AB  - Delirium is a frequent syndrome among patients who are elderly. People who are
      older with cognitive impairment who are institutionalized are at increased risk
      of developing delirium when hospitalized. In addition, their prior cognitive
      impairment makes detecting their delirium a challenge. This study goal was to
      describe the effect of severity of prior cognitive impairment on delirium
      prevalence and symptom presentation among patients who were older and were newly
      admitted to an acute care hospital. A total of 104 were included in this
      descriptive study and screened for delirium. The results showed that the
      prevalence of delirium increased according to the severity of the patients' prior
      cognitive impairment. Except for disorganized thinking, all symptoms of delirium
      were similar among patients with mild, moderate, and severe prior cognitive
      impairment. The study concluded that training nurses to recognize subtle changes
      in mental status among those patients who were older with prior cognitive
      impairment may prevent the underdetection of delirium.

PMID- 16410621
TI  - Family caregivers and transition to long-term care.
AB  - This study's purpose was to explore family caregivers' experiences while they
      waited placement of family members with dementia in long-term care and how they
      coped during this period of waiting and transition. In this exploratory
      descriptive qualitative study, interviews were conducted with 29 caregivers at
      entry to the placement wait-list and at 3 to 4-month intervals thereafter. Final
      interviews, with 15 caregivers, were conducted shortly after admission to long
      term care. When "the waiting begins," the themes of crisis as initiator,
      synchronicity, control, and reciprocity emerged. "After placement" included the
      themes of deeply bonded relationships, attempting continuity, and sorting out the
      change. The findings provide new insight into family caregiver experiences during
      and after placement of a family member with dementia in long-term care.
      Clinicians must recognize that wherever services are provided, at home before
      placement or in institutions after placement, family caregivers must be
      incorporated as full partners in care.

PMID- 16410623
TI  - Pilot using World Wide Web to prevent diabetes in adolescents.
AB  - This pilot study tested the effects of an interactive nutrition education Web
      site on fruit, vegetable, and fat consumption in minority adolescents genetically
      at risk for Type 2 diabetes. A one-group nonexperimental pretest, posttest focus
      group design was used. Twenty-one sixth-grade to eighth-grade junior high
      adolescents who were minorities volunteered to participate. Participants received
      5 hours of Web-based nutrition education over 3 weeks. A significant difference
      in fat consumption was supported from the computerized dietary assessment. No
      difference was found in fruit or vegetable consumption. Comparative data
      indicated a rise in body mass index (BMI) percentile from 88.03 (1999) to 88.40
      (2002; boys) and 88.25 (1999) to 91.2 (2002; girls). Focus group responses
      supported the satisfaction of adolescents in the study with the use of the Web
      based intervention for nutrition education. Healthy eating interventions using
      Web-based nutrition education should be further investigated with adolescents.

PMID- 16410624
TI  - Acquired disorders of reading and writing: cross-script comparisons.

PMID- 16410625
TI  - Deep dysgraphia in Turkish.
AB  - Deep dysgraphic patients make semantic errors when writing to dictation and they
      cannot write nonwords. Extant reports of deep dysgraphia come from languages with
      relatively opaque orthographies. Turkish is a transparent orthography because the
      bidirectional mappings between phonology and orthography are completely
      predictable. We report BRB, a biscriptal Turkish-English speaker who has acquired
      dysgraphia characterised by semantic errors as well as effects of grammatical
      class and imageability on writing in Turkish. Nonword spelling is abolished. A
      similar pattern of errors is observed in English. BRB is the first report of
      acquired dysgraphia in a truly transparent writing system. We argue that deep
      dysgraphia results from damage to the mappings that are common to both languages
      between word meanings and orthographic representations.

PMID- 16410626
TI  - Acquired surface alexia in Spanish: a case report.
AB  - This paper reports a case study of acquired surface alexia in Spanish and
      discusses the most suitable tests to detect this syndrome in a writing system
      that is very regular for reading at the segmental and supra-segmental levels.
      Patient MM has surface alexia characterized by quantitatively good performance in
      reading words and pseudowords; accurate but slow and syllabic reading of words,
      nonwords and sentences; good performance in lexical decision tasks including
      words and nonwords; errors in lexical decision with pseudohomophones; and
      homophone confusions. This pattern of reading can be interpreted as a disorder in
      the lexical reading route and overdependence on the non-lexical route. We discuss
      nonlexical impairments and the interpretation of alexia and suggest tasks to
      identify surface alexia in a shallow orthography.

PMID- 16410627
TI  - Acquired dyslexia in Spanish: a review and some observations on a new case of
      deep dyslexia.
AB  - Readers and writers of Spanish use an orthography that is highly transparent. It
      has been proposed that readers of Spanish can rely on grapheme-phoneme
      correspondences, alone, to access meaning or phonology from print. In recent
      years, a number of case studies have yielded evidence inconsistent with this
      idea. We review these studies with particular focus on those that report evidence
      for reading based on direct lexical mappings between print, orthographic
      representations, and meaning or phonology. We report a new case of acquired
      literacy impairment in Spanish, MJ, who presents a pattern of preserved abilities
      and deficits symptomatic of deep dyslexia. The patient is unable to read
      nonwords, but can read a substantial number of words. Her reading is
      characterized by the production of semantic, visual, and derivational errors. We
      argue that MJ has a deficit in her lexical selection ability, common to both her
      reading and her naming problems. We propose that MJ, and the other cases we
      review, demonstrate that lexical reading is adopted by skilled readers even in a
      transparent language.

PMID- 16410628
TI  - Frequency effects with visual words and syllables in a dyslexic reader.
AB  - The present study investigated the nature of the inhibitory syllable frequency
      effect, recently reported for normal readers, in a German-speaking dyslexic
      patient. The reading impairment was characterized as a severe deficit in naming
      single letters or words in the presence of spared lexical processing of visual
      word forms. Three visual lexical decision experiments were conducted with the
      dyslexic patient, an unimpaired control person matched to the patient and a
      control group: Experiment 1 manipulated the frequency of words and word-initial
      syllables and demonstrated systematic effects of both factors in normal readers
      and in the dyslexic patient. The syllable frequency effect was replicated in a
      second experiment with a more strictly controlled stimulus set. Experiment 3
      confirmed the patient's deficit in activating phonological forms from written
      words by demonstrating that a pseudohomophone effect as observed in the
      unimpaired control participants was absent in the dyslexic patient.

PMID- 16410629
TI  - Multiple levels of letter representation in written spelling: evidence from a
      single case of dysgraphia with multiple deficits.
AB  - In this paper, we report a detailed analysis of the impaired performance of a
      dysgraphic individual, AD, who produced similar rates of letter-level errors in
      written spelling, oral spelling, and typing. We found that the distribution of
      various letter error types displayed a distinct pattern in written spelling on
      the one hand and in oral spelling and typing on the other. In particular,
      noncontextual letter substitution errors (i.e., errors in which the erroneous
      letter that replaces the target letter does not occur elsewhere within the word)
      were virtually absent in oral spelling and typing and mainly found in written
      spelling. In contrast, letter deletion errors and multiple-letter errors were
      typically found in oral spelling and very exceptional in written spelling. Only
      contextual letter substitution errors (i.e., errors in which the erroneous letter
      that replaces the target letter is identical to a letter occurring earlier or
      later in the word) were found in similar proportions in the three tasks. We argue
      that these contrasting patterns of letter error distribution result from damage
      to two distinct levels of letter representation and processing within the
      spelling system, namely, the amodal graphemic representation held in the
      graphemic buffer and the letter form representation computed by subsequent
      writing-specific processes. Then, we examined the relationship between error and
      target in the letter substitution errors produced in written and oral spelling
      and found evidence that distinct types of letter representation are processed at
      each of the hypothetized levels of damage: symbolic letter representation at the
      graphemic level and representation of the component graphic strokes at the letter
      form processing level.

PMID- 16410630
TI  - Letter form as a constraint for errors in neglect dyslexia and letter position
      dyslexia.
AB  - Does letter-form constrain errors in peripheral dyslexia? In Hebrew, 5 of the 22
      letters have two different letter forms, one is used only when the letter occurs
      in word-final position, the other form is used in initial and middle positions.
      Is the information on final-forms encoded in the letter identity information and
      used for word identification, or is it discarded? The current research explored
      this question through the effect of final vs. non final letter form on the error
      pattern in neglect dyslexia (neglexia) and letter position dyslexia (LPD). Left
      word-based neglexia results in errors of omission, substitution and addition of
      letters in the left side of words, which in Hebrew is the end of the word. We
      examined whether final letter form blocks the addition of letters to the end of
      the word and whether omissions of letters after letters in non-final form are
      avoided. The predominant error type in LPD is migration of letters within words.
      We tested whether migrations also occur when they cause form change of either
      final-form letters that move to middle position or middle-form letters that move
      to final position. These questions were assessed in both acquired and
      developmental neglexia and LPD. The results indicated a strong effect of final
      letter-form on acquired neglexia and on acquired and developmental LPD, which
      almost completely prevented form-changing errors. This effect was not found in
      developmental neglexia, where words that end in final-form letters were actually
      more impaired than other words, probably because final-form letters appear only
      on the neglected side of the word for Hebrew-reading children with left
      developmental neglexia. These data show that early visuo-orthographic analysis is
      sensitive to final letter form and that final letter form constrains errors in
      peripheral dyslexia.

PMID- 16410631
TI  - Acquired dyslexia and dysgraphia in Chinese.
AB  - Understanding how the mappings between orthography and phonology in alphabetic
      languages are learned, represented and processed has been enhanced by the
      cognitive neuropsychological investigation of patients with acquired reading and
      writing disorders. During the past decade, this methodology has been extended to
      understanding reading and writing in Chinese leading to new insights about
      language processing, dyslexia and dysgraphia. The aim of this paper is to review
      reports of patients who have acquired dyslexia and acquired dysgraphia in Chinese
      and describe the functional architecture of the reading and writing system. Our
      conclusion is that the unique features of Chinese script will determine the
      symptoms of acquired dyslexia and dysgraphia in Chinese.

PMID- 16410632
TI  - Whole-word phonological representations of disyllabic words in the Chinese
      lexicon: data from acquired dyslexia.
AB  - This study addresses the issue of the existence of whole-word phonological
      representations of disyllabic and multisyllabic words in the Chinese mental
      lexicon. A Cantonese brain-injured dyslexic individual with semantic deficits,
      YKM, was assessed on his abilities to read aloud and to comprehend disyllabic
      words containing homographic heterophonous characters, the pronunciation of which
      can only be disambiguated in word context. Superior performance on reading to
      comprehension was found. YKM could produce the target phonological forms without
      understanding the words. The dissociation is taken as evidence for whole-word
      representations for these words at the phonological level. The claim is
      consistent with previous account for discrepancy of the frequencies of tonal
      errors between reading aloud and object naming in Cantonese reported of another
      case study of similar deficits. Theoretical arguments for whole-word form
      representations for all multisyllabic Chinese words are also discussed.

PMID- 16410633
TI  - The selective impairment of the phonological output buffer: evidence from a
      Chinese patient.
AB  - We present a Chinese-speaking patient, SJ, who makes phonological errors across
      all tasks involving oral production. Detailed analyses of the errors across
      different tasks reveal that the patterns are very similar for reading, oral
      picture naming, and repetition tasks, which are also comparable to the error
      patterns of the phonological buffer deficit cases reported in the literature. The
      nature of the errors invites us to conclude that the patient's phonological
      output buffer is selectively impaired. Different from previously reported cases,
      SJ's deficits in oral production tasks are not accompanied by a similar
      impairment of writing performance. We argue that this dissociation is evidence
      that the phonological output buffer is not involved in writing Chinese words.
      Furthermore, the majority of SJ's errors occur at the onset of a syllable,
      indicating that the buffer has a structure that makes the onset more prone to
      impairment.

PMID- 16410634
TI  - Phosphorylation of peptides derived from isolated soybean protein: effects on
      calcium binding, solubility and influx into Caco-2 cells.
AB  - Calcium homeostasis in the human body is maintained primarily via the absorption
      of calcium through the intestine. In order to maintain an efficient absorption of
      calcium with minimal calcium loss due to the formation of calcium phosphate
      precipitates in the small intestinal lumen, we developed a calcium-binding
      mediator using peptides derived from isolated soybean protein (ISP). ISP was
      modified via tryptic digestion and chemical phosphorylation using sodium
      trimetaphosphate, thereby generating soybean phosphopeptides (SPP), and this was
      followed by conducting a binding reaction with calcium chloride. We have
      established an optimized procedure and reaction conditions for maximal
      phosphorylation and calcium binding. Consequently, the phosphorylation of soybean
      peptides resulted in considerable improvement in their calcium binding
      activities. Next, we demonstrated that SPP was able to render calcium ions
      resistant to precipitate formation with inorganic phosphates, which suggested the
      enhancement of calcium bioavailability. Finally, we noted that the addition of
      calcium-bound SPP induced an increase in cytosolic calcium concentration in the
      intestinal Caco-2 cells, due to an influx of calcium. These findings provide a
      new basis by which we may assess the possibility that SPP, as a potent calcium
      carrier, can be utilized in the prevention of poor absorption of dietary calcium
      in animals.

PMID- 16410635
TI  - The effect of lycopene on cell growth and oxidative DNA damage of Hep3B human
      hepatoma cells.
AB  - Lycopene, the predominant carotenoid in tomatoes and tomato-based foods, is
      reported to protect against various cancers, especially prostate cancer. We
      investigated the effect of lycopene on DNA damage and cell growth inhibition in
      the Hep3B human hepatoma cell line. Lycopene was analyzed by HPLC, and cell
      proliferation was determined by 3-(4,5-dimethylthiazolyl-2)-2,5
      diphenyltetrazolium bromide (MTT) assay. A final lycopene concentration of 0.1-50
      microM was added to cells plated in 96-well plates. After a 24-hr incubation,
      cell viability was measured as absorbance at 570 nm after the MTT assay. The
      effects of lycopene on cell cycle progression were investigated with flow
      cytometry. Lycopene induced G0/G1 arrest and S phase block. Oxidative DNA damage
      was determined by the Comet (single-cell gel electrophoresis) assay. Lycopene
      inhibited cell growth in a dose-dependent manner. Cell growth was inhibited 20%
      at 0.2 microM lycopene and 40% at 50 microM lycopene after a 24-hr incubation. In
      the Comet assay, lycopene-treated cells showed less DNA damage than did placebo
      treated cells. The inhibition of Hep3B cell growth in this study demonstrates the
      antitumor properties of lycopene.

PMID- 16410636
TI  - Extraction and chromatographic separation of anticarcinogenic fractions from
      cacao bean husk.
AB  - The utilization of cacao bean husk (CBH), a by-product of chocolate manufacture,
      would be both environmentally and economically beneficial. For this purpose, a
      process for effectively separating and fractionating CBH fractions having cancer
      preventive potential was developed in this study. For screening the fractions
      with potent cancer preventive activity, we examined the effect of extracts and
      fractions of CBH on the inhibition of gap-junction intercellular communication
      (GJIC) and the DNA synthesis of cancer cells, both of which are characteristics
      of the promotion and progression stages in carcinogenesis. The extracts of CBH
      (especially, the 60% ethanol fraction after extraction with 50% acetone)
      containing 43 wt.% polyphenol exerted an excellent protective effect on H2O2
      induced inhibition of GJIC in WB-F344 rat liver epithelial cells as determined by
      the scrape-loading/dye transfer assay. The enhancement of GJIC by the extracts of
      CBH was approximately 10-fold higher than that of a well-known dietary
      chemopreventive component, vitamin C. The extracts of CBH (especially, the 60%
      ethanol fraction) also suppressed DNA synthesis in all liver, stomach, and colon
      cancer cells as demonstrated by the ;3H-thymidine incorporation assay, by
      approximately four-fold higher than that of vitamin C. These results imply that
      the polyphenol extracts and fractions of CBH are effective functional materials
      to be used in either preventing or inhibiting cancer.

PMID- 16410637
TI  - Role of selenium in regulation of spermatogenesis: involvement of activator
      protein 1.
AB  - Selenium (Se) is involved in the process of male reproduction. Several studies
      have been carried out to find the mechanism of Se action through identified
      selenoproteins. Especially selenoenzyme phospholipid glutathione peroxidase
      (PHGPx, GPx-4) plays a pivotal role in regulating spermatogenesis. However, the
      action of selenium is best known as an antioxidant which acts through various
      selenoproteins viz. glutathione peroxidase, thioredoxin reductase and
      selenoprotein P. Oxidative stress is currently being considered a leading cause
      of male infertility. Presently, the involvement of redox active transcription
      factor, AP1 (Activator protein1) in testicular function was studied. AP1 is redox
      sensitive and also controls cell proliferation. The effects of Se might be
      mediated through it. Different Se status - deficient, adequate and excess Se -
      were generated in male Balb/c mice by feeding yeast based selenium deficient diet
      and deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se),
      respectively, for a period of 4 and 8 weeks. Se status was checked by measuring
      the Se levels and glutathione peroxidase (GSH-Px) activity in testis and liver.
      The reproductive potential of mice was affected at these changed Se levels.
      Changes in the activity of superoxide dismutase (SOD), levels of reduced
      glutathione (GSH) and oxidized glutathione (GSSG) were observed indicating
      increased oxidative stress at both the levels. Further, changes in the mRNA
      expression of GSH-Px, gamma-glutamylcysteine synthetase gammaGCS) and Mn
      superoxide dismutase (MnSOD) were observed. Decrease in cjun and cfos mRNA levels
      were observed at both the Se status (deficient and excess) which might be
      responsible for decreased germ cell number, differentiation and reduced fertility
      observed at the altered Se levels.

PMID- 16410638
TI  - Traditional Chinese Medicine improves dysfunction of peroxisome proliferator
      activated receptor alpha and microsomal triglyceride transfer protein on
      abnormalities in lipid metabolism in ethanol-fed rats.
AB  - We report the effects of Traditional Chinese Medicine (TCM) on alcohol-induced
      fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba,
      Crataegus pinnatifida, Alisma oriental, Salvia miltiorrhiza and Pueraria lobata.
      The rats were separated randomly into five groups; the CD group (n=10), which was
      fed a control diet for 10 weeks, the ED group (n=10), which was fed an isocaloric
      liquid diet containing ethanol for 10 weeks and given daily oral doses of TCM
      (0.222 g/kg/day; TCM222, 0.667 g/kg/day; TCM667, and 2.000 g/kg/day; TCM2000,
      n=10, respectively) over the last four weeks of the study. The ED group developed
      fatty livers, as determined by their lipid profiles and liver histological
      findings. Compared with the control group, liver/body weight, plasma triglyceride
      (TG) and total cholesterol (TC), liver TG and TC, plasma alanine aminotransferase
      (ALT) and aspartic aminotransferase (AST) significantly increased in the ED
      group. Also, free fatty acids (FFA) levels increased in both plasma and liver
      during the administration of ethanol. On the other hand, when rats were
      administrated with TCM, their liver/body weight, plasma TG, TC and FFA, liver TG,
      TC and FFA, plasma ALT and AST decreased significantly and the degree of hepatic
      lipid droplets was markedly improved compared with those in the ED group. Proper
      function of the peroxisome proliferator-activated receptor alpha (PPARalpha) is
      essential for the regulation of hepatic fatty acid metabolism. Microsomal
      triglyceride transfer protein (MTP) is essential for the secretion of
      triglycerides from the liver. mRNAs for PPARalpha and MTP were reduced in the
      livers of ethanol-fed rats. TCM restored the mRNA levels of PPARalpha and MTP,
      and prevented development of fatty livers in ethanol-fed rats. Impairment of
      PPARalpha and MTP function during ethanol consumption contributes to the
      development of alcohol-induced fatty liver, which can be overcome by TCM.

PMID- 16410639
TI  - Comparative in vitro wear testing of PEEK and UHMWPE capped metacarpophalangeal
      prostheses.
AB  - Six metacarpophalangeal prostheses were each wear tested to five million cycles.
      Each prosthesis consisted of a metacarpal component with an approximately
      hemispherical shell on a titanium body, articulating against a titanium
      phalangeal component. Four prostheses had a shell made from ultra-high molecular
      weight polyethylene (UHMWPE) and two had a shell made from polyether ether ketone
      (PEEK). The tests were undertaken using a finger wear simulator. Despite pre
      soaking and the use of control components, lubricant uptake by the metacarpal
      components was significant. Gravimetrically, the UHMWPE test components showed a
      greater weight gain than the UHMWPE control components. Therefore there was no
      apparent wear of any of the UHMWPE test metacarpal components. The original
      concentric machining marks of the UHMWPE components could still be seen after
      five million cycles of testing. For the metacarpal components with PEEK shells,
      gravimetric wear could be measured. Gravimetrically, all of the titanium
      phalangeal components showed little or no wear. Light scratches in the direction
      of sliding appeared on the articulating faces of all metacarpal and phalangeal
      test components, indicating slight abrasive wear.

PMID- 16410640
TI  - Residual stress in bone structure and tissue of rabbit's tibiofibula.
AB  - This paper presents an X-ray diffraction method of measuring the residual
      stress/strain in bone tissue of rabbit's tibia. To derive the residual stress,
      bone powder of the diameter less than 40 micrometers was used as a control
      specimen at non-stressed state. From the X-ray measurements, it was clear that
      the distribution of residual stress existed in the bone tissue. The tensile
      residual stress at bone axial direction occurred in the proximal-medial region of
      rabbit's tibia. The compressive stress occurred in the other regions. In
      addition, the mechanism to generate the residual stress was investigated by
      sequential cutting of the tibiofibula system from bone structure scale to bone
      tissue scale. The remodeling is a phenomenon that the bone structure adapts
      functionally to mechanical environment. The residual stress will become a
      mechanical trigger to induce the remodeling.

PMID- 16410641
TI  - Bone formation-promoting effect of genistein on marrow mesenchymal cell culture.
AB  - The effect of genistein, a soybean isoflavone, on new bone formation by bone
      marrow cells from mature rats and humans was examined. Bone marrow cells were
      collected from the femoral diaphysis of 7-week-old Fisher rats, cultured in MEM
      containing fetal calf serum and then cultured with or without the addition of
      dexamethasone to the bone-forming medium. Genistein was added at concentrations
      of 10(-5),10(-6),10(-7) or 10(-8) M. Bone formation was examined 2 weeks after
      culture. After informed consent was obtained from a 55-year-old woman with lumbar
      spondylosis deformans, bone marrow cells were collected from her ilium for
      culture by the same process, and bone formation investigated. In both rats and
      humans, when dexamethasone was added to the bone-forming medium, genistein (10(
      7) M and 10(-8) M) caused a significant increase in the levels of calcium,
      alkaline phosphatase, and DNA compared with cells not cultured in genistein. In
      conclusion, genistein was found to promote bone formation at lower concentrations
      across species, and thus may be useful as a bone formation-promoting factor.

PMID- 16410642
TI  - Preparation of germanium apatite and its cytotoxicity.
AB  - Germanium apatite was synthesized via the solid-state reaction between GeO(2) and
      (NH(4))(3)PO(4). The synthesized materials were characterized using XRD, and
      thermal analysis was carried out using TG-DTA. Ge(2)P(2)O(7) was preferentially
      produced at temperatures between 300-900 degrees C, and at temperatures above
      1000 degrees C, germanium apatite (Ge(5)O(PO(4))(6), GeAp) was synthesized. In
      solubility tests, 0.36% and 0.65% of Ge ions were liberated from GeAp powder in
      distilled water at 37 and 80 degrees C after four weeks, respectively. A GeAp
      aqueous solution maintained at 37 degrees C was strongly acidic with a pH=1.67
      after four weeks. The growth rate of human adult gingival fibroblast cells in a
      medium that included GeAp, HA, and GeO(2) was investigated. The growth rate of
      the cells in a 0.1 mg/ml GeAp medium was almost the same as that in the control.
      The cell growth was restricted in a 1.0 mg/ml GeAp medium, whereas the cell
      growth in a pH-adjusted 1.0 mg/ml GeAp medium at pH=7.60 was higher than that in
      non-adjusted medium at pH = 7.06.

PMID- 16410643
TI  - Habituation to treadmill walking.
AB  - The use of a treadmill to evaluate gait patterns makes it possible to analyze
      many gait cycles and stride to stride variations. The objective of this study was
      to assess the time required for a subject to habituate to walking on a treadmill.
      The evolution of knee kinematics and spatio-temporal parameters were analyzed to
      measure habituation to walking on the treadmill. To obtain this information, data
      were recorded on 10 healthy subjects for about 45 minutes as they walked on a
      treadmill. A steady state was attained for knee kinematics and most spatio
      temporal parameters at the time the treadmill had attained its maximal speed
      (approximately 30 seconds). However, 10 minutes were necessary for stride length
      to become reproducible. Time for habituation to walking on a treadmill must be
      considered when kinematics are evaluated during gait of healthy and disabled
      subjects. We have shown that, at least for young, healthy individuals who are non
      naive to walking on a treadmill, a 10-minute warm-up is enough before three
      dimensional knee kinematics and spatio-temporal data can be recorded.

PMID- 16410644
TI  - Estimation of the viscous properties of skin and subcutaneous tissue in uniaxial
      stress relaxation tests.
AB  - Knowledge of viscoelastic properties of soft tissues is essential for the finite
      element modelling of the stress/strain distributions in finger-pad during
      vibratory loading, which is important in exploring the mechanism of hand-arm
      vibration syndrome. In conventional procedures, skin and subcutaneous tissue have
      to be separated for testing the viscoelastic properties. In this study, a novel
      method has been proposed to simultaneously determine the viscoelastic properties
      of skin and subcutaneous tissue in uniaxial stress relaxation tests. A
      mathematical approach has been derived to obtain the creep and relaxation
      characteristics of skin and subcutaneous tissue using uniaxial stress relaxation
      data of skin/subcutaneous composite specimens. The micro-structures of collagen
      fiber networks in the soft tissue, which underline the tissue mechanical
      characteristics, will be intact in the proposed method. Therefore, the
      viscoelastic properties of soft tissues obtained using the proposed method would
      be more physiologically relevant than those obtained using the conventional
      method. The proposed approach has been utilized to measure the viscoelastic
      properties of soft tissues of pig. The relaxation curves of pig skin and
      subcutaneous tissue obtained in the current study agree well with those in
      literature. Using the proposed approach, reliable material properties of soft
      tissues can be obtained in a cost- and time-efficient manner, which
      simultaneously improves the physiological relevance.

PMID- 16410645
TI  - Three-dimensional reconstruction and quantitative analysis of the brain stem
      nuclei based on fast centroid auto-registration.
AB  - This paper introduces a three-dimensional (3D) reconstruction algorithm of the
      brain stem nuclei based on fast centroid auto-registration. The research is based
      on methods and theories of computer stereo vision, and by image information
      processing three-point pattern local search, registration and auto-tracing for
      the centroids of the brain stem nuclei were accomplished. We adopt two-peak
      threshold, edge detection and grayscale image enhancement to extract contours of
      the nuclei's structures. The experimental results obtain the spatial structure
      information and 3D image of the brain stem nuclei, show spatial relationship
      between 14 pairs of nuclei, and quantitate morphological parameters of each type
      of nuclei's 3D structure. This work is significant to neuroanatomy research and
      clinic applications. Furthermore, a software system named BRAIN.HUK is
      established.

PMID- 16410646
TI  - A study of maternal hemodynamic change during healthy pregnancy and women with
      gestation hypertension.
AB  - OBJECTIVE: To investigate the maternal hemodynamic changes that occurs during
      pregnancy. To find out the difference that lie in healthy pregnancy and women
      with gestational hypertension. To introduce a method that is applied to shift
      high-risk women of gestational hypertension in pregnancy women. METHOD: Serial
      hemodynamic investigations (total 8 times) were performed throughout pregnancy
      period by radioulnar pulse wave electrical monitoring in 182 women (130 with
      healthy pregnancies, 52 with gestational hypertension). Analysis of variance with
      repeated measurements was used to evaluate the course of a number of hemodynamic
      indices. To identify the correlation between these changes and gestational
      hypertension by using above method. RESULTS: A significant difference in mean
      arterial pressure (MAP), cardiac output (CO), cardiac index (CI), total
      Peripheral Resistance (TPR) and heart rat (HR) was observed different between
      normal pregnancy and women with gestational hypertension. The changes of
      parameters in normal woman and gestational hypertension were recorded and the
      mechanism of gestational hypertension was heterogenous. CONCLUSION: These results
      provide sensitive parameters for use in early risk assessment and as a guide to
      preventive intervention during pregnancy.

PMID- 16410648
TI  - Altered glutathione redox state in schizophrenia.
AB  - Altered antioxidant status has been reported in schizophrenia. The glutathione
      (GSH) redox system is important for reducing oxidative stress. GSH, a radical
      scavenger, is converted to oxidized glutathione (GSSG) through glutathione
      peroxidase (GPx), and converted back to GSH by glutathione reductase (GR).
      Measurements of GSH, GSSG and its related enzymatic reactions are thus important
      for evaluating the redox and antioxidant status. In the present study, levels of
      GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains
      from schizophrenic patients and control subjects (with and without other
      psychiatric disorders). Significantly lower levels of GSH, GPx, and GR were found
      in schizophrenic group than in control groups without any psychiatric disorders.
      Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group.
      Moreover, both GSSG and GR levels were significantly and inversely correlated to
      age of schizophrenic patients, but not control subjects. No significant
      differences were found in any GSH redox measures between control subjects and
      individuals with other types of psychiatric disorders. There were, however,
      positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR
      levels in control subjects without psychiatric disorders. These positive
      correlations suggest a dynamic state is kept in check during the redox coupling
      under normal conditions. By contrast, lack of such correlations in schizophrenia
      point to a disturbance of redox coupling mechanisms in the antioxidant defense
      system, possibly resulting from a decreased level of GSH as well as age-related
      decreases of GSSG and GR activities.

PMID- 16410649
TI  - Protein analysis in human cerebrospinal fluid: Physiological aspects, current
      progress and future challenges.
AB  - The introduction of lumbar puncture into clinical medicine over 100 years ago
      marks the beginning of the study of central nervous system diseases using the
      human cerebrospinal fluid (CSF). Ever since, CSF has been analyzed extensively to
      elucidate the physiological and biochemical bases of neurological disease. The
      proximity of CSF to the brain makes it a good target for studying the
      pathophysiology of brain functions, but the barrier function of the CSF also
      impedes its diagnostic value. Today, measurements to determine alterations in the
      composition of CSF are central in the differential diagnosis of specific diseases
      of the central nervous system (CNS). In particular, the analysis of the CSF
      protein composition provides crucial information in the diagnosis of CNS
      diseases. This enables the assessment of the physiology of the blood-CSF barrier
      and of the immunology of intrathecial responses. Besides those routine
      measurements, protein compositional studies of CSF have been extended recently to
      many other proteins in the expectation that comprehensive analysis of lower
      abundance CSF proteins will lead to the discovery of new disease markers. Disease
      marker discovery by molecular profiling of the CSF tissue has the enormous
      potential of providing many new disease relevant molecules. New developments in
      protein profiling techniques hold promise for the discovery and validation of
      relevant disease markers. In this review, we summarize the current efforts and
      progress in CSF protein profiling measurements using conventional and current
      protein analysis tools. We also discuss necessary development in methodology in
      order to have the highest impact on the study of the molecular composition of CSF
      proteins.

PMID- 16410650
TI  - The process chain for peptidomic biomarker discovery.
AB  - Over the last few years the interest in diagnostic markers for specific diseases
      has increased continuously. It is expected that they not only improve a patient's
      medical treatment but also contribute to accelerating the process of drug
      development. This demand for new biomarkers is caused by a lack of specific and
      sensitive diagnosis in many diseases. Moreover, diseases usually occur in
      different types or stages which may need different diagnostic and therapeutic
      measures. Their differentiation has to be considered in clinical studies as well.
      Therefore, it is important to translate a macroscopic pathological or
      physiological finding into a microscopic view of molecular processes and vice
      versa, though it is a difficult and tedious task. Peptides play a central role in
      many physiological processes and are of importance in several areas of drug
      research. Exploration of endogenous peptides in biologically relevant sources may
      directly lead to new drug substances, serve as key information on a new target
      and can as well result in relevant biomarker candidates. A comprehensive analysis
      of peptides and small proteins of a biological system corresponding to the
      respective genomic information (peptidomics(R)methods) was a missing link in
      proteomics. A new peptidomic technology platform addressing peptides was recently
      presented, developed by adaptation of the striving proteomic technologies. Here,
      concepts of using peptidomics technologies for biomarker discovery are presented
      and illustrated with examples. It is discussed how the biological hypothesis and
      sample quality determine the result of the study. A detailed study design,
      appropriate choice and application of technology as well as thorough data
      interpretation can lead to significant results which have to be interpreted in
      the context of the underlying disease. The identified biomarker candidates will
      be characterised in validation studies before use. This approach for discovery of
      peptide biomarkes has potential for improving clinical studies.

PMID- 16410651
TI  - Identification of disease markers in human cerebrospinal fluid using lipidomic
      and proteomic methods.
AB  - Lipids comprise the bulk of the dry mass of the brain. In addition to providing
      structural integrity to membranes, insulation to cells and acting as a source of
      energy, lipids can be rapidly converted to mediators of inflammation or to
      signaling molecules that control molecular and cellular events in the brain. The
      advent of soft ionization procedures such as electrospray ionization (ESI) and
      atmospheric pressure chemical ionization (APCI) have made it possible for
      compositional studies of the diverse lipid structures that are present in brain.
      These include phospholipids, ceramides, sphingomyelin, cerebrosides, cholesterol
      and their oxidized derivatives. Lipid analyses have delineated metabolic defects
      in disease conditions including mental retardation, Parkinson's Disease (PD),
      schizophrenia, Alzheimer's Disease (AD), depression, brain development, and
      ischemic stroke. In this review, we examine the structure of the major lipid
      classes in the brain, describe methods used for their characterization, and
      evaluate their role in neurological diseases. The potential utility of
      characterizing lipid markers in the brain, with specific emphasis on disease
      mechanisms, will be discussed. Additionally, we describe several proteomic
      strategies for characterizing lipid-metabolizing proteins in human cerebrospinal
      fluid (CSF). These proteins may be potential therapeutic targets since they
      transport lipids required for neuronal growth or convert lipids into molecules
      that control brain physiology. Combining lipidomics and proteomics will enhance
      existing knowledge of disease pathology and increase the likelihood of
      discovering specific markers and biochemical mechanisms of brain diseases.

PMID- 16410652
TI  - Central neurochemical ultradian variability in depression.
AB  - Depression is characterized by blunted behavior and neuroendocrine function that
      generally improve with antidepressant treatment. This study examined intrinsic
      variability in brain neurotransmitter function, since it may be a source of
      blunted behavior and neuroendocrine function in depression and a marker for the
      illness, and has not previously been analyzed using wavelet decomposition. To
      measure variability in monoamine metabolites, lumbar cerebrospinal fluid (CSF)
      was collected in serial samples in depressed patients before and after treatment.
      We hypothesized that changes in variability would be observed after treatment.
      Mechanisms that control such variability may be critical to the pathophysiology
      of depression. METHOD: Time series data was obtained from serial ten-min sampling
      over a 24-hr period (N=144) from thirteen depressed patients, with a repeat
      collection after 5 weeks of antidepressant (sertraline or bupropion) treatment.
      Concentrations of tryptophan (TRP), the monoamine metabolites 5-HIAA (metabolite
      of serotonin) and HVA (metabolite of dopamine), and the HVA:5HIAA ratio were
      transformed to examine power in slowly (160 min/cycle) to rapidly (20 min/cycle)
      occurring events. Power, the sum of the squares of the coefficients in each d
      (detail) wavelet, reflects variability within a limited frequency bandwidth for
      that wavelet. Pre-treatment to post-treatment comparisons were conducted with
      repeated measures ANOVA. RESULTS: Antidepressant treatment was associated with
      increased power in the d2 wavelet from the HVA (p=0.03) and the HVA:5-HIAA ratio
      (p=0.03) series. The d1 and d3 wavelets showed increased power following
      antidepressant treatment for the ratio series (d1, p=0.01; d3, p=0.05).
      Significant changes in power were not observed for the 5-HIAA data series. Power
      differences among analytes suggest that the findings are specific to each system.
      CONCLUSION: The wavelet transform analysis shows changes in neurochemical signal
      variability following antidepressant treatment. Patterns or degrees of
      variability may be as important as, or possibly more important than, the mean
      levels of monoamine transmitters. Studies of variability observed in healthy
      individuals and a larger depressed sample will be needed to verify a relationship
      with mood and treatment response. Neurochemical measures of time-variability may
      be a pivotal marker in depression.

PMID- 16410654
TI  - Microglia activation in the brain as inflammatory biomarker of Alzheimer's
      disease neuropathology and clinical dementia.
AB  - The role of microglia-mediated inflammation in the progression of Alzheimer's
      disease (AD) neuropathology remains unclear. In this study, postmortem brain
      sections from AD and control cases were subjected to Human Leukocyte Antigen
      (HLA)-DR immunohistochemistry to examine microglia activation in the progression
      of AD assessed by pre-mortem clinical dementia rating (CDR) and postmortem
      pathological manifestations of neuritic plaque (NP) and neurofibrillary tangle
      (NT) according to the Consortium to Establish a Registry for Alzheimer's Disease
      (CERAD). In both gray and white matter of the entorhinal cortex (EC) and HLA-DR
      immunostaining increased with the progression of CDR or CERAD NP, and to a lesser
      degree with CERAD NT. Between CDR stages HLA-DR significance was found in
      moderate (CDR 2) to severe dementia (CDR 5) where as between CERAD NP stages
      staining increased significantly from NP 0 (no plaque) to NP 1 (sparse plaques),
      suggesting increased microglia activation begins with amyloid NP deposition. In
      the hippocampus, a significant increase in microglia immunostaining was found in
      the pyramidal cell layer of CA1 as early as CDR 1, and in the upper molecular
      layer of the dentate gyrus in CDR 0.5. This increase continues with the
      progression of CDR and reaches maximum in CDR 5. When assessed by CERAD NP stages
      however, a significant increase in microglia immunostaining was found only in mid
      to-late stages (NP 3) and reduced staining was seen in NP 5. These results
      suggest that microglia activation increases with the progression of AD, with the
      increase varying depending on the involved brain region.

PMID- 16410653
TI  - Prostaglandin D synthase isoforms from cerebrospinal fluid vary with brain
      pathology.
AB  - Glutathione independent prostaglandin D synthase (Swissprot P41222, PTGDS) has
      been identified in human cerebrospinal fluid and some changes in PTGDS in
      relation to disease have been reported. However, little is known of the extent
      that PTGDS isoforms fluctuate across a large range of congenital and acquired
      diseases. The purpose of this study was to examine changes in PTGDS isoforms in
      such a population. Spinal fluid from 22 healthy study participants (normal
      controls) with no classifiable neurological or psychiatric diagnosis was obtained
      and PTGDS isoforms were identified by specific immunostaining and mass
      spectrometry after denaturing 2D gel electrophoresis. The PTGDS isoforms in
      controls consisted of five charge isoforms that were always present and a small
      number of occasional, low abundance isoforms. A qualitative survey of 98
      different people with a wide range of congenital and acquired diseases revealed
      striking changes. Loss of the control isoforms occurred in congenital
      malformations of the nervous system. Gain of additional isoforms occurred in some
      degenerative, most demyelinating and vasculitic diseases, as well as in
      Creutzfeldt-Jakob disease. A retrospective analysis of published data that
      quantified relative amounts of PTGDS in multiple sclerosis, schizophrenia and
      Parkinson's disease compared to controls revealed significant dysregulation. It
      is concluded that qualitative and quantitative fluctuations of cerebrospinal
      fluid PTGDS isoforms reflect both major and subtle brain pathophysiology.

PMID- 16410655
TI  - Cerebellar metastasis as first metastasis from papillary thyroid carcinoma.
AB  - Brain metastasis is an uncommon complication of differentiated thyroid carcinoma.
      Even more, cerebellar metastases from papillary thyroid carcinoma (PTC) are
      exceptional. We report a 69-year-old male patient with infiltrative PTC who
      developed high levels of thyroglobulin (Tg) and deteriorated neurological
      symptoms four years after the initial diagnosis. Computerized tomography (CT) of
      the brain demonstrated a cerebellar mass and the patient underwent surgery.
      Pathology revealed metastasis from PTC. Immunochemistry was positive for Tg. The
      patient had no other sites of distant metastases. Although PTC has generally a
      good prognosis, metastases to the cerebellum can occur, even as the first
      metastatic site, despite the fact that appropriate therapy (surgery, radioactive
      iodine therapy, TSH suppression therapy, chemotherapy and external radiotherapy)
      had been given for the primary tumour.

PMID- 16410656
TI  - Effects of age, grip strength and smoking on forearm volumetric bone mineral
      density and bone geometry by peripheral quantitative computed tomography:
      comparisons between female and male.
AB  - Peripheral quantitative computed tomography (pQCT) is useful to measure
      volumetric bone mineral density (vBMD) distinguishing trabecular from cortical
      bones as well as quantity of bone geometry. In the present study, we examined the
      effects of age, grip strength and smoking on vBMD, bone geometry and bone
      strength index (polar strength strain index (SSIp)), and then compared with the
      differences between female and male by employing pQCT in Japanese 252 female and
      230 male subjects. Age was negatively correlated with vBMD, cortical area (Ct.Ar)
      and cortical thickness (Ct.Th) as well as SSIp in both sexes, and the correlation
      coefficients were higher in female, compared with those in male. Although age was
      correlated with endocortical circumferences (En.Le) in both sexes, periosteal
      circumferences (Ex.Le) were correlated with age only in male. Volumetric BMD,
      Ct.Ar, Ct.Th and SSIp were significantly lower in the group with vertebral
      fractures, although En.Le and Ex.Le were similar between subjects with and
      without vertebral fractures. Grip strength was positively correlated with vBMD,
      Ct.Ar, Ct.Th as well as SSIp. The extent of correlation was much higher in
      female, compared with that in male. Ct.vBMD, Ct.Ar, Ct.Th and SSIp, but not
      trabecular vBMD, were significantly lower in the group with high Brinkman index
      (number of cigarettes smoked per day) x (duration of smoking (years)) in female.
      These parameters were not significantly different between groups with high and
      low Brinkman index in male. In conclusion, the present study demonstrated that
      age, grip strength and smoking affected forearm vBMD, bone geometry and bone
      strength index by pQCT. These effects were greater in female, compared with those
      in male.

PMID- 16410657
TI  - Early changes in biochemical markers of bone turnover predict bone mineral
      density response to antiresorptive therapy in Korean postmenopausal women with
      osteoporosis.
AB  - Biochemical markers of bone turnover have been suggested to be useful in
      monitoring the efficacy of antiresorptive therapy. In this study, we investigated
      the predictive value of bone turnover markers to determine short-term response in
      bone mineral density (BMD) and to identify nonresponders in 138 postmenopausal
      women (mean age 58 years) with osteoporosis given with either hormone thearpy
      (HT) or alendronate. Urinary type I collagen N-telopeptide (NTx) and serum
      osteocalcin (OC) at baseline, 3, and 6 months after treatment as well as spine
      and femoral neck BMD at baseline and 12 months were measured. Significant
      decreases in both NTx and OC were evident in women on treatment with
      antiresorptive agents as early as 3 months (p<0.01). Percent change of NTx at 3
      months correlated with the percent change of spinal BMD at 12 months of
      treatment. When bone turnover markers were stratified by tertiles, the average
      rate of lumbar spine BMD gain increased significantly with increasing tertiles of
      baseline value (p<0.05) and percent change (p<0.05) of urinary NTx at 3 month of
      treatment. In terms of BMD response, urinary NTx at 3 months decreased
      significantly more in BMD responders group than in nonresponders group. Logistic
      regression analysis demonstrated that percent change of NTx at 3 months is an
      independent predictor to identify BMD nonresponders, defined as those whose BMD
      gain remained within the precision error range of dual energy X-ray
      absorptiometer (DXA). We conclude that biochemical markers of bone turnover,
      especially percent change in urinary NTx levels, can be used to determine BMD
      response to antiresorptive therapy in Korean postmenopausal women with
      osteoporosis.

PMID- 16410658
TI  - Olfactory neuroblastoma causing ectopic ACTH syndrome.
AB  - A 39-year-old woman who presented with typical Cushingoid appearance (moon
      facies, central obesity, purpura) was admitted to our hospital because of
      pulmonary infection. She was found to have hypertension, severe hypokalemia, and
      metabolic alkalosis. Endocrine data revealed elevated plasma levels of ACTH and
      cortisol with lack of circadian rhythm, non-suppressibility to high-dose
      dexamethasone, and hyperresponsiveness to CRH stimulation. Although no pituitary
      mass was detected by MRI of the brain, inferior petrosal sinus sampling showed a
      step-up of central to peripheral ACTH levels; these data are consistent with the
      diagnosis of Cushing's disease. She was successfully treated with metyrapone to
      control hypercortisolemia. Ten months later, a mass was detected in the ethmoid
      sinus, which was surgically removed. After resection of the ethmoid sinus tumor,
      her Cushingoid features and hypercortisolemia disappeared, but recurred after
      enlargement of a second mass in the maxillary sinus. After resection of the
      maxillary sinus tumor, her hypercortisolemia subsided. Histologically, the tumor
      tissues from both the ethmoid and maxillary sinus were identical and consistent
      with the diagnosis of olfactory neuroblastoma. Immunohistochemically, the
      immunoreactivities of ACTH and POMC were positive in the cytoplasm of tumor
      cells, and immunoreactive ACTH was demonstrated in both tumor tissues. Thus, this
      is the second rare case with ectopic ACTH syndrome caused by olfactory
      neuroblastoma thus far reported.

PMID- 16410659
TI  - Characteristics of Japanese subjects who progress from normal to impaired glucose
      tolerance. Longitudinal study excluding changes in body weight.
AB  - In this retrospective longitudinal study, we focused on the clinical
      characteristics of Japanese individuals with recent onset impaired glucose
      tolerance (IGT) who have been followed up for insulin secretory function and 75
      gram oral glucose tolerance test (OGTT) for more than 3 years annually before
      they progressed from normal glucose tolerance (NGT) to IGT. Subjects whose body
      weight did not show significant change for the period were selected and labeled
      as either NGT (no change in OGTT over 3 years) or IGT (progressors from NGT to
      IGT) groups (n = 24, each). We compared the basal biochemical data and response
      of plasma glucose and serum insulin after OGTT of the two groups. In the IGT
      progressors, significant increase of plasma glucose at 30 to 120 minutes during
      OGTT and significant decrease of HDL-cholesterol were observed since 3 years
      before onset of IGT. In addition to increase of serum glucose and decrease of HDL
      cholesterol, serum insulin at 120 minutes during OGTT were significantly and
      remarkably high at onset and 3 years before onset of IGT. Plasma glucose at 30
      120 minutes and serum insulin level at 120 minutes after glucose load are
      potentially significant predictors of progression from NGT to IGT even in
      subjects who do not show increase of body weight.

PMID- 16410660
TI  - Association of antipituitary antibody and type 2 iodothyronine deiodinase
      antibody in patients with autoimmune thyroid disease.
AB  - Antipituitary antibody (APA) has been reported to be detected in patients with
      autoimmune thyroid disease. Type 2 iodothyronine deiodinase (D2) is expressed in
      both pituitary gland and thyroid gland. We studied the association of APA and D2
      peptide antibody in patients with autoimmune thyroid disease. Rat pituitary gland
      homogenate and D2 peptide were used as antigens in the present study. APA and D2
      peptide antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in
      sera obtained from 42 patients with Hashimoto's disease, 26 patients with Graves'
      disease and 70 healthy control subjects. Moreover, D2 activity precipitation
      assay was performed in some patients with Hashimoto's disease. APA and D2 peptide
      antibody were elevated in patients with Hashimoto's disease and patients with
      Graves' disease, compared with control subjects. APA was positive in 32.4%
      (22/68), D2 peptide antibody was positive in 26.5% (18/68) of patients with
      autoimmune thyroid disease. APA was positive in 31.0% (13/42) of patients with
      Hashimoto's disease and 34.6% (9/26) of patients with Graves' disease. D2 peptide
      antibody was positive in 26.2% (11/42) of patients with Hashimoto's disease and
      26.9% (7/26) of patients with Graves' disease. D2 peptide antibody was correlated
      with APA in patients with autoimmune thyroid disease. Moreover, precipitation of
      D2 activity was increased in some patients with Hashimoto's disease including a
      patient who also had idiopathic diabetes insipidus, and was correlated with D2
      peptide antibody. These results suggest that D2 antibody may be associated with
      APA in patients with autoimmune thyroid disease.

PMID- 16410661
TI  - Clinical features of bone metastases resulting from thyroid cancer: a review of
      28 patients over a 20-year period.
AB  - Bone is the second most frequent site of metastasis resulting from thyroid
      cancer. Many studies have investigated clinical features and prognostic factors
      of distant metastases stemming from thyroid cancer in Western countries. The
      purpose of this study was to review clinical characteristics of Korean patients
      with bone metastasis originating from thyroid cancer. Between January 1985 and
      August 2004, 28 patients with thyroid cancer were diagnosed with bone metastases
      at the Yonsei Severance Hospital in Seoul, Korea. Their clinical characteristics
      were analyzed retrospectively. Incidence of bone metastasis from follicular
      thyroid cancer was 6.8% (9 of 132 patients), and 0.4% (13 of 3,154 patients) from
      papillary thyroid cancer, with an odds ratio of 17.67 (95% confidence interval;
      7.41-42). Twelve patients had no symptoms of bone metastasis. Overall mean number
      of metastasis sites was 2.6 +/- 1.9, and 12 patients had a solitary bone
      metastasis. Survival rates between the synchronous and metachronous metastasis
      groups were not significantly different, and the number of metastasis sites did
      not affect survival. However, the survival of patients that underwent curative
      treatment was longer than those with palliation (P = 0.0317). In Korea, the
      overall incidence of bone metastasis resulting from thyroid cancer was less than
      our expectation. Many patients were asymptomatic, and had a tendency of
      undergoing less aggressive or palliative treatment, even though the long-term
      survival of distant metastasis resulting from thyroid cancer with active
      treatment is relatively good. Further studies of the prognostic factors and
      effectiveness of various treatments of these patients are needed to enhance
      survival.

PMID- 16410662
TI  - Massive cardiac thrombosis in a patient with Sheehan's syndrome.
AB  - Growth hormone deficiency (GHD) is a risk factor for increased cardiovascular
      disease, and it has been recently demonstrated that abnormalities in coagulation
      system might contribute to the increased cardiovascular morbidity and mortality.
      However, there is not enough data related to the major thrombotic events in GH
      deficient patients. We describe the case of a 62-year-old woman with Sheehan's
      syndrome who developed massive cardiac thrombosis. She was hospitalized with
      acute pulmonary edema. ECG revealed high ventricular responsive atrial
      fibrillation (AF) and T-wave inversion on precordial leads. The ejection fraction
      of left ventricle (LVEF) was measured as 60% by transthoracic echocardiography
      (TTE) and there was 2nd degree mitral regurgitation with concentric hypertrophic
      LV walls. Transesophagial echocardiography (TEE) established thrombi both at
      right atrium and left atrial appendix. Before anticoagulant therapy several
      hemostatic and fibrinolytic markers were measured. Except increased D-dimer
      concentration (763.14 mug/L (0-325)) we did not observe any pathological finding
      in these parameters. After 14 days of discharge, the patient was admitted to the
      intensive care unit with upper gastrointestinal bleeding. The warfarin and
      salicylate were stopped for two months. At the end of two months, the patient was
      again hospitalized with congestive heart failure and there was a high ventricular
      responsive AF on ECG. TEE was performed and three thrombi were demonstrated at
      right atrium (RA), left atrium (LA) and left ventricle (LV). There was no active
      bleeding on upper GIS endoscopy and anticoagulant therapy was restarted. In this
      particular case massive cardiac thrombi involving three chambers (LA, RA, LV)
      were more extensive than expected in AF. Moreover, there was a 2nd degree mitral
      regurgitation in the patient, and based on previous studies mitral regurgitation
      has been associated with less prevalent LA spontaneous echo contrast and fewer
      thromboembolic events. Therefore we hypothesized that severe GHD in the present
      case might be the major contributing factor in massive cardiac thrombosis. In
      summary, based on previous data there is increased risk of thromboembolic events
      in GHD although the mechanism is unclear yet. Our case is the first case showing
      massive cardiac thrombosis in a severe GH-deficient patient with Sheehan's
      syndrome. Therefore, patients with GHD should be screened carefully for thrombus
      in clinical practice, and further studies need to be done to understand the
      relation between GHD and coagulation system.

PMID- 16410663
TI  - Parathyroid hormone response to tracheal intubation in hyperparathyroid patients
      and normal subjects.
AB  - The stress of direct laryngoscopy and passing an endotracheal tube through the
      vocal cords elicits haemodynamic, metabolic and hormonal changes such as raising
      blood catecholamine levels. Catecholamines are known stimulants of PTH secretion.
      The effect of tracheal intubation on plasma parathyroid hormone levels has not
      yet been investigated. We monitored changes in plasma parathyroid hormone levels
      before and after tracheal intubation in 72 hyperparathyroid patients undergoing
      elective parathyroidectomy for primary and secondary hyperparathyroidism. These
      findings were compared to data collected from 20 subjects who underwent elective
      surgery (thyroidectomy or laparoscopic cholecystectomy) under general anesthesia.
      In the control group, tracheal intubation significantly increased plasma
      parathyroid hormone levels from 59 +/- 31 pg/ml to 91 +/- 40 pg/ml (mean +/- SD)
      (p<0.0003). In primary hyperparathyroid patients, the identical procedure
      increased plasma parathyroid hormone levels from 206 +/- 104 pg/ml to 217 +/- 113
      pg/ml (p = 0.12) and from 898 +/- 495 pg/ml to 1162 +/- 613 pg/ml (p = 0.07) in
      secondary hyperparathyroidism patients. We concluded that tracheal intubation
      raises plasma parathyroid hormone levels. The mechanism underlying this response
      requires further investigation.

PMID- 16410664
TI  - Role of adrenalectomy in ectopic ACTH syndrome.
AB  - Evaluation of adrenalectomy in patients diagnosed with ectopic ACTH syndrome was
      studied. Twenty-three clinical cases diagnosed with ectopic ACTH syndrome were
      analyzed at Chinese Academy of Medical Sciences and Peking Union Medical College
      Hospital (PUMCH). Cases consisted of 14 males and 9 females, with mean age of 38
      years. All 23 cases had positive clinical, biochemical and radiology evidence for
      diagnosis of Cushing's syndrome. Sixteen of the 23 cases were treated with total
      adrenalectomy and the remaining 7 were treated without surgical intervention.
      Sixteen cases, having no identifiable source of ectopic hormone production,
      experienced resolution of presenting signs and symptoms after undergoing
      bilateral or unilateral total adrenalectomy; 1-year survival was 67%, 2-year
      survival 41% and 5-year survival 15%. In patients treated conservatively without
      surgical intervention, 1-year survival was 0%. In patients with no identifiable
      source of ectopic hormone production, bilateral adrenalectomy followed by hormone
      replacement treatment is effective.

PMID- 16410665
TI  - Effects of dehydroepiandrosterone on gluconeogenic enzymes and glucose uptake in
      human hepatoma cell line, HepG2.
AB  - Dehydroepiandrosterone (DHEA), the most abundant human adrenal steroid, improves
      insulin sensitivity and obesity in human and model animals. In a previous study,
      we reported that orally administered DHEA suppresses the elevated activities of
      hepatic gluconeogenic enzymes like glucose-6-phosphatase (G6Pase) in C57BL/KsJ
      db/db mice. However, the molecular mechanisms by which DHEA ameliorates insulin
      resistance are not clearly understood. In the present study, we cultured the
      human hepatoma cell line HepG2 with DHEA and measured the enzyme activity and
      protein expression of G6Pase to investigate the direct effect of DHEA on glucose
      metabolism in hepatocytes. DHEA significantly suppressed both the activity and
      protein expression of G6Pase. Moreover, DHEA decreased the gene expression of
      G6Pase and phosphoenolpyruvate carboxykinase, both of which were maximal at 1
      microM DHEA, whereas the mRNA level of glucose-6-phosphate translocase was
      unchanged. Furthermore, DHEA enhanced 2-deoxyglucose uptake, although its effect
      was much smaller than that of insulin. These results suggest that DHEA may act at
      multiple steps in the regulation of glucose metabolism in the liver.

PMID- 16410666
TI  - Effect of high dose methylprednisolone pulse therapy followed by oral
      prednisolone administration on the production of anti-TSH receptor antibodies and
      clinical outcome in Graves' disease.
AB  - Little is known about the immunosuppressive effect of glucocorticoids on TSH
      receptor antibodies. We observed the long-term prognosis and serum TSH binding
      inhibitor immunoglobulin (TBII) levels in patients with Graves' ophthalmopathy
      who had received intravenous methylprednisolone pulse therapy (pulse therapy)
      followed by oral prednisolone administration in order to ascertain how long the
      immunosuppressive effect of glucocorticoids continued. This is the first report
      on the effect of pulse therapy on Graves' disease outcome. We observed 67
      patients who were treated by antithyroid drugs (ATD) alone for 2 years after
      pulse therapy. TBII was evaluated before and 3, 6, 12, 18, and 24 months after
      pulse therapy. The mean TBII decreased significantly 3 months after pulse therapy
      (p<0.001), and was maintained until 24 months. There were 24 patients whose TBII
      was positive (>15%) at 24 months, in whom the mean TBII decreased significantly 3
      to 6 months after pulse therapy (p<0.001), but increased again at 12 to 24 months
      (p<0.05). Thus, the immunosuppressive effect of glucocorticoids may be lost at 12
      months after pulse therapy in these patients. The remission rate in the pulse
      therapy group was 40.98%, and that of the control patient group was 48.57%. There
      was no significant difference between the two. These results suggest that the
      immunosuppressive effect of pulse therapy was temporary, and that pulse therapy
      did not increase remission rate of Graves' disease.

PMID- 16410667
TI  - Malignant gastric carcinoid causing ectopic ACTH syndrome: discrepancy of plasma
      ACTH levels measured by different immunoradiometric assays.
AB  - Discrepancy of plasma ACTH levels measured by different immunoradiometric assays
      (IRMA) in a case with malignant gastric carcinoid causing ectopic ACTH syndrome
      was examined by gel chromatography and immunohistochemical analysis. A 49-year
      old male was found to have a large gastric tumor, with muscle wasting,
      hypertension, diabetes and hypokalemia caused by hypercortisolemia. His plasma
      ACTH levels, although initially elevated, were found to be almost in normal
      ranges. The discrepancy of plasma ACTH levels was proven to be due to different
      IRMA kits used; the initial assay was performed by a kit that could recognize
      high-molecular weight (HMW) form as well as ACTH(1-39), but the later assay by
      another kit that could recognize only ACTH(1-39). Pathological examination of the
      gastric tumor was consistent with the diagnosis of malignant carcinoid.
      Immunohistochemical study revealed that immunoreactivity of proopiomelanocortin
      (POMC) was positive within the tumor cells, whereas those of ACTH and prohormone
      convertase 1/3 were negative. Molecular sieving analysis of patient's plasma by
      gel chromatography coupled with ACTH radioimmunoassay which could recognize HMW
      form and ACTH(1-39) and two different IRMAs revealed that the predominant form of
      ACTH was HMW form with a minor peak of ACTH(1-39). This is a rare case of ectopic
      ACTH syndrome caused by malignant gastric carcinoid with preferential production
      of HMW form of ACTH, possibly due to unprocessed POMC.

PMID- 16410668
TI  - High risk of osteopenia and bone derangement in postsurgical patients with
      craniopharyngiomas, pituitary adenomas and other parasellar lesions.
AB  - Hypopituitarism is a well-known cause of secondary osteoporosis. However,
      patients receiving surgery for pituitary tumors or parasellar lesions have not
      been well studied for their bone sequel in Japan. We measured bone mineral
      density (BMD) and urinary type I collagen N-telopeptide (uNTX) in 35
      postoperative patients including 25 with pituitary tumor (PT), 6 with
      craniopharyngioma (CP), and 4 others who had not been on sex hormone replacement,
      raloxifene, or bisphosphonate therapy. Compared with patients with PT, patients
      with CP had lower BMD and higher uNTX. Five out of 6 patients with CP had BMD
      lower than 80% of young adult mean (YAM), whereas 11 out of 22 patients with PT
      had BMD less than 80% of YAM. Patients with CP had significantly lower serum
      levels of gonadotropins, and they also tended to have lower serum levels of sex
      steroids, although statistically not significantly. Two postoperative patients
      with CP on sex steroid replacement, who were not included in the current
      analysis, had normal BMD. Of all the subjects, the prominent difference between
      patients with normal BMD and normal value of uNTX and patients with low BMD and
      elevated uNTX value was that the latter received higher dose of hydrocortisone
      replacement. The present study confirms postsurgical patients with pituitary or
      parasellar lesions, especially those with CP, are at high risk for osteopenia. In
      designing replacement therapy for those patients, it is important to consider
      bone by minimizing the dose of glucocorticoid, including sex steroids, and using
      other drugs that protect bone.

PMID- 16410669
TI  - Current status of clinical care for familial endocrine tumor syndromes in Japan.
AB  - We performed nationwide questionnaire-based surveys to characterize the current
      status of medical services for endocrine tumor syndromes, such as multiple
      endocrine neoplasia (MEN) and von Hippel-Lindau disease (VHL), in Japan. About
      30% of the respondents had seen patients with either MEN or VHL, but the number
      of patients most of respondents had encountered was 5 or fewer. On the other
      hand, a large number of patients had been seen in a few hospitals, which seemed
      to be the result of the availability of specialists, rather than of geographic
      location. Although nearly 90% of hospitals had performed genetic tests, less than
      half of the hospitals had a clinical genetics division that provided genetic
      counseling to patients and/or family members. Not all of the respondents were
      thoroughly familiar with the "Guidelines for genetic testing" proposed by the
      consortium of Japanese genetic-medicine-related societies in 2003. Only 27.8% of
      respondents have read the guidelines and understood their concepts.

PMID- 16410670
TI  - Mechanisms of TRH-induced GH release (paradoxical response) in human somatotroph
      adenoma cells.
AB  - The mechanisms of paradoxical TRH response in human somatotroph adenoma cells
      were investigated using intracellular calcium measurement and static incubation
      assay. Intracellular calcium measurement revealed that TRH induces a biphasic
      response: a transient increase followed by a sustained plateau. The transient
      phase was due to the calcium release from IP(3)-regulated intracellular calcium
      store and the subsequent sustained phase was due to the calcium influx through
      the voltage-gated calcium channels. The signal transduction mechanism of the
      calcium plateau involved protein kinase C. These calcium responses, especially
      the second phase, was responsible for the TRH-induced GH release.

PMID- 16410671
TI  - Mechanism of adrenomedullin-induced prolactin release from human prolactin
      releasing adenoma cells.
AB  - The mechanism of adrenomedullin-induced prolactin release was investigated in
      prolactin-secreting human pituitary adenoma cells by intracellular calcium
      measurement and static incubation study. Adrenomedullin stimulated prolactin
      release in a concentration-dependent manner. The stimulation was dependent on
      extracellular sodium and voltage-gated calcium channels. PKA inhibitor attenuated
      adrenomedullin-induced prolactin release. The mechanism of adrenomedullin action
      was studied by fura 2-based intracellular calcium measurement. Adrenomedullin
      increased intracellular calcium concentration in these cells. The increase was
      dependent on extracellular sodium and voltage-gated calcium channels. PKA
      inhibitor attenuated the calcium response. These data indicate that
      adrenomedullin stimulates prolactin release by modulating calcium influx through
      voltage-gated calcium channels dependently on extracellular sodium. Mechanisms
      involving sodium-influx mediated depolarization may play a role in the
      stimulatory action.

PMID- 16410672
TI  - Mechanism of D(2) agonist-induced inhibition of GH secretion from human GH
      secreting adenoma cells.
AB  - The mechanism of dopamine D(2) agonist-induced inhibition of GH secretion from GH
      secreting adenoma cells was investigated by measurement of intracellular calcium
      concentration ([Ca(2+)] (i)) and static incubation experiment. Bromocriptine
      decreased [Ca(2+)](i) in a concentration-dependent manner through D(2) receptor.
      The inhibition was abolished by pertussis toxin pretreatment. Bromocriptine did
      not decrease [Ca (2+)](i) after nitrendipine had decreased it. 8Br-cAMP increased
      [Ca(2+)](i) but application of bromocriptine decreased it, suggesting that
      bromocriptine-induced inhibition of [Ca(2+)](i) is not dependent on bromocriptine
      induced inhibition of adenylyl cyclase. Static incubation experiment revealed
      that bromocriptine inhibited GH secretion in a concentration-dependent manner.
      The inhibition was through D(2) receptor and was abolished by pertussis toxin
      pretreatment. 8Br-cAMP increased GH secretion. Bromocriptine decreased GH
      secretion even after 8Br-cAMP pretreatment. However, the GH release from cells
      incubated with bromocriptine alone was significantly less than that from cells
      incubated with bromocriptine after 8Br-cAMP pretreatment, suggesting a modulatory
      action of cAMP system in bromocriptine response.

PMID- 16410673
TI  - Association of common LH variant with hyperfunctional promoter in a Japanese
      infertile woman.
AB  - A common LH variant (V-LH) with Trp8Arg and Ile15Thr is often associated with
      ovarian dysfunction primarily in the Japanese population, and the LHB gene
      encoding V-LH is linked with a hyperfunctional promoter that could partly
      compensate for the somewhat weak biological effect of the V-LH in the Finnish and
      other several populations. We analyzed the promoter region in a Japanese
      infertile woman homozygous for the V-LH, to examine whether the hyperfunctional
      promoter is present or absent in the Japanese V-LH carriers with ovarian
      dysfunction. Direct sequencing was performed for a 661 bp promoter region from -8
      to -668 bp of LHB, revealing homozygosity for eight nucleotide substitutions (
      238A>G, -276G>A, -489C>A, -490T>A, -504T>A, -506T>C, -525T>G, and -552C>T) that
      are identical to those found in the hyperfunctional promoter. The results suggest
      that ovarian dysfunction frequently observed in the Japanese V-LH carriers would
      be due to some population-specific genetic and/or environmental factor(s) rather
      than to the lack of the hyperfunctional promoter and the resultant low biological
      effect of the V-LH. In addition, the tight linkage between the two missense
      substitutions in the coding region and the eight nucleotide substitutions in the
      promoter region of LHB appears to be common to various ethnic groups.

PMID- 16410674
TI  - Abrupt enlargement of adrenal incidentaloma: a case of isolated adrenal
      metastasis.
AB  - A 56-year-old Japanese man was referred for examination of right adrenal tumor (3
      cm). He had no apparent preexisting cancer by radiological workup and
      accordingly, the patient was considered as a nonfunctioning adrenocortical
      adenoma and scheduled for periodic CT scans every 6 months. However, five months
      after the initial diagnosis the patient complained of severe right back pain with
      remarkable enlargement of both adrenals (~20-fold volume). Although the origin of
      adrenal tumor was uncertain by pathological workup, positron emission tomography
      (PET) scan with (18)F-2-fluoro-D-deoxyglucose (FDG) eventually revealed a hot
      spot on left upper lung, which was consistent with a lesion of thickened bulla
      wall observed by chest CT. The present case is a very rare example of abrupt
      enlargement of bilateral adrenals due to clinically isolated adrenal metastasis,
      suggesting the requirement of frequent observation with greatest care regarding
      morphologic changes of adrenal incidentalomas.

PMID- 16410675
TI  - Effect of cyclosporin a on immediate early gene in rat global ischemia and its
      neuroprotection.
AB  - The expressions of the immediate early genes, c-fos and c-jun, and their product
      proteins C-FOS, C-JUN, and P-JUN were examined in the hippocampal CA1 subfield
      after global ischemia and reperfusion in rats treated with cyclosporin A. More
      than 90% neuronal cell death was seen in hippocampal CA1 7 days after global
      ischemia in control animals, but only 5% cell death after ischemia was seen in
      the CsA-treated animals. The expressions of c-fos and c-jun mRNA in the control
      animals were detected with an increase from 1 to 48 h after ischemia. On the
      other hand, they showed significant suppression in the CsA-treated animals.
      Increased expressions of C-FOS were found 1, 24, and 48 h after reperfusion in
      the control animals. In the CsA-treated animals C-FOS expression was found to
      increase, but the expression level reduced to a statistically insignificant level
      within 48 h after the ischemia. C-JUN and P-JUN expressions increased in control
      animals, but were almost completely suppressed in the CsA-treated animals. The
      present study demonstrated that the suppressant effects of CsA on IEGs and their
      products might have causal relationship to the dramatic protecting effect of the
      drug against delayed neuronal cell death.

PMID- 16410676
TI  - Relationship of intracellular calcium and oxygen radicals to Cisplatin-related
      renal cell injury.
AB  - We investigated the involvement of reactive oxygen species (ROS) and
      intracellular calcium in nephrotoxicity related to an antitumor agent, cisplatin.
      In this study, we employed cultured renal epithelial cells (LLC-PK1). Cisplatin
      at 500 microM significantly increased the production of ROS 5 h and caused cell
      injury. This agent significantly increased the intracellular calcium level
      ([Ca2+]i) in a dose-dependent manner 1 h or more after exposure. DPPD (N,N'
      diphenyl-p-phenylenediamine), an antioxidant, inhibited a cisplatin-related
      increase in active oxygen production and cell injury but did not inhibit an early
      increase in the [Ca2+]i level. An intracellular calcium-chelating compound BAPTA
      AM (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)
      ester) inhibited an increase in ROS production and cell injury induced by
      cisplatin. Furthermore, BAPTA-AM suppressed the rise of [Ca2+]i level in 1 h
      after exposure; however, an extracellular calcium chelator EGTA and a calcium
      antagonist nicardipine did not inhibit the rise in [Ca2+]i level in the early
      phase. An NADPH oxidase inhibitor inhibited a cisplatin-related increase in ROS
      production and cell disorder. These results suggest that cisplatin-related
      calcium release from the site of intracellular calcium storage in the early phase
      causes oxidative stress in renal tubular epithelial cells. Cisplatin may increase
      the intracellular production of ROS via NADPH oxidase.

PMID- 16410677
TI  - Effect of clarithromycin on the pharmacokinetics of cabergoline in healthy
      controls and in patients with Parkinson's disease.
AB  - Cabergoline is used in the treatment of Parkinson's disease (PD). Clarithromycin
      is a potent inhibitor of CYP3A4 and P-glycoprotein and is often co-administered
      with cabergoline in usual clinical practice. We studied the effect of
      clarithromycin co-administration on the blood concentration of cabergoline in
      healthy male volunteers and in PD patients. Study 1: Ten healthy male volunteers
      were enrolled and were randomized to take a single oral dose of cabergoline (1
      mg/day) for 6 days or a single oral dose of cabergoline plus clarithromycin (400
      mg/day) for 6 days. Study 2: Seven PD patients receiving stable cabergoline doses
      were enrolled. They were evaluated for the plasma cabergoline concentration
      before and after the addition of clarithromycin 400 mg/day for 6 days, and again
      1 month after discontinuation of clarithromycin. The dose and duration of
      clarithromycin were decided according to usual clinical practice. In healthy male
      volunteers, mean Cmax and AUC(0-10 h) of cabergoline increased to a similar
      degree during co-administration of clarithromycin. Mean plasma cabergoline
      concentration over 10 h post-dosing increased 2.6-fold with clarithromycin co
      administration. In PD patients, plasma cabergoline concentration increased 1.7
      fold during clarithromycin co-administration. Co-administration with
      clarithromycin may increase the blood concentration of cabergoline in healthy
      volunteers and in PD patients.

PMID- 16410678
TI  - Galanin fiber hypertrophy within the cholinergic nucleus basalis during the
      progression of Alzheimer's disease.
AB  - Galanin (GAL)-containing fibers enlarge and hyperinnervate remaining cholinergic
      basal forebrain (CBF) neurons within the anterior nucleus basalis (NB) in late
      stage Alzheimer's disease (AD). Whether GAL hypertrophy occurs in the CBF in the
      prodromal or early stages of AD remains unknown. The present study used GAL
      immunohistochemistry and an unbiased semiquantitative scoring method to evaluate
      GAL innervation in the anterior NB of subjects clinically diagnosed as having no
      cognitive impairment, mild cognitive impairment or early-stage (mild/moderate)
      AD. There was no difference in GAL fiber staining within the anterior NB across
      the three clinical groups examined. Furthermore, GAL fiber innervation was not
      correlated with the number of NB neurons expressing the nerve growth factor
      receptors p75(NTR) or TrkA or with cortical choline acetyltransferase activity in
      the same cases. Single-cell gene expression analysis demonstrated that
      cholinergic NB neurons express mRNA for the GAL receptors GALR1, GALR2 and GALR3,
      yet the levels of these mRNAs were unchanged across the three diagnostic groups.
      These observations indicate that GAL hypertrophy within the anterior NB subfield
      is a late-stage AD response, which may play a role in regulating the cholinergic
      tone of remaining basocortical projection neurons.

PMID- 16410679
TI  - Ribavirin levels and haemoglobin decline in early virological responders and non
      responders to hepatitis C virus combination therapy.
AB  - Therapeutic drug monitoring of ribavirin has been claimed to predict virological
      response and/or haematological side effects in patients with chronic hepatitis C
      undergoing peginterferon/ribavirin combination treatment. In the present study,
      steady-state ribavirin levels were retrospectively analyzed in serum samples from
      patients at week 12 of combination therapy with peginterferon alpha-2a or alpha
      2b and ribavirin. Patients were classified as early virological responders on the
      basis of undetectable HCV-RNA or HCV-RNA drop >or=2 log from baseline at week 12.
      The mean ribavirin level was not different between early virological responders
      (2.3 +/- 0.1 microg/ml, n = 45) and early virological non-responders (2.0 +/- 0.2
      microg/ml, n = 10). There was no correlation between ribavirin levels at week 12
      and early virological response. In patients with early virological response,
      haemoglobin (Hb) levels were found to be decreased by 18% on average from the
      basal values; however, in only 2 patients Hb levels declined below 100 g/l. There
      was a moderate negative correlation between ribavirin levels and Hb levels at
      week 12 (R = -0.50, p < 0.001); however, ribavirin levels did not correlate with
      relative or absolute decline in Hb as compared to basal levels or with ribavirin
      dose per kilogram body weight. In addition, a significant negative correlation
      between ribavirin levels and glomerular filtration rate was found (R = -0.31, p <
      0.05). Based on our results, monitoring of ribavirin serum levels at week 12 of
      HCV combination therapy does not appear to predict early virological response or
      reductions in Hb levels. Further research is needed to assess their diagnostic
      value at other time points of peginterferon/ribavirin combination treatment
      and/or in patients with renal insufficiency.

PMID- 16410680
TI  - Homocysteine-induced endothelin-1 release is dependent on hyperglycaemia and
      reactive oxygen species production in bovine aortic endothelial cells.
AB  - BACKGROUND: Elevated plasma homocysteine (Hcy) is a risk factor for coronary
      disease. The objective of this study was to investigate whether Hcy either alone
      or in high glucose conditions induces endothelin-1 (ET-1) synthesis via the
      production of reactive oxygen species (ROS). METHODS: Bovine aortic endothelial
      cells were grown in high (25 mmol/l) and low (5 mmol/l) glucose medium. RESULTS:
      In high glucose, Hcy caused a time-dependent increase in ET-1 release, which was
      greatest with 50 micromol/l Hcy at 24 h (p < 0.01). This effect was not seen in
      low glucose conditions. In high glucose and 50 micromol/l Hcy, ET-1 mRNA levels
      were maximal after 1 h (p < 0.05). Tissue factor mRNA levels were raised at 4 h
      (p < 0.05) and functional activity was raised at 6 h (p < 0.01). Intracellular
      ROS production was increased by 50 micromol/l Hcy after 24 h (p < 0.05) but only
      in high glucose. To investigate the role of mitochondrial metabolism in ROS
      production, cells were incubated with thenoyltrifluoroacetone (inhibitor of
      complex II) or carbonyl cyanide m-chlorophenylhydrazone (uncoupler of oxidative
      phosphorylation). Both compounds abolished the Hcy-induced increase in ROS
      production and ET-1 release. There was an alteration in intracellular glutathione
      (GSH) levels with Hcy treatment with more oxidised GSH present. CONCLUSION: The
      combined metabolic burden of Hcy and high glucose stimulates ET-1 synthesis in
      bovine aortic endothelial cells via a mechanism dependent on the production of
      mitochondrial ROS, but may not be generalisable to all types of endothelial
      cells.

PMID- 16410681
TI  - Synergistic suppression of rat neointimal hyperplasia by rapamycin and imatinib
      mesylate: implications for the prevention of accelerated arteriosclerosis.
AB  - BACKGROUND: Accelerated arteriosclerosis remains a major limitation to
      therapeutic interventions such as angioplasty, stent deployment, and solid organ
      transplantation. Rapamycin, a powerful new immunosuppressant set to replace
      calcineurin inhibitors in the transplant setting, and imatinib mesylate, a
      receptor tyrosine kinase inhibitor, are both angioprotective. Here, we explored
      the pharmacological and therapeutic interactions of these two agents in a rat
      model of neointimal hyperplasia. METHODS: Wistar rats, subjected to balloon
      catheter-induced aortic injury, received daily drug treatment until postoperative
      day 14 and were subsequently sacrificed or followed up to day 40 without further
      treatment. Development of neointimal lesions was assessed histologically and
      immunohistochemically. Steady-state rapamycin levels in whole blood were
      determined by HPLC-UV. RESULTS: Rapamycin and imatinib, administered individually
      or in combination, produced no signs of overt toxicity. Continuous postoperative
      therapy with either rapamycin (0.5-1.5 mg/kg/day) or imatinib (2- 50 mg/kg/day)
      dose-dependently suppressed neointimal hyperplasia on day 14. Combined treatment
      (0.5 or 1 + 10 mg/kg/day, respectively) showed a trend towards synergistic action
      on day 14. Withdrawal of medication on day 14 nullified the early therapeutic
      effect of either agent by day 40. In contrast, early combination therapy (1 + 10
      mg/kg/day) achieved long-term suppression of neointimal hyperplasia by
      approximately 81%. Notably, coadministration of imatinib appeared to reduce
      exposure to rapamycin, although this finding did not reach statistical
      significance. CONCLUSIONS: Short-term combination therapy with rapamycin and
      imatinib is well tolerated and produces synergistic, sustained suppression of
      neointimal hyperplasia in rats. Subject to clinical evaluation, this new drug
      regimen may afford definitive prophylaxis against accelerated arteriosclerosis.

PMID- 16410682
TI  - Continuous endothelial cell activation increases angiogenesis: evidence for the
      direct role of endothelium linking angiogenesis and inflammation.
AB  - There is increasing evidence that chronic inflammation is tightly linked to
      diseases associated with endothelial dysfunction, including the induction of
      aberrant angiogenesis. While leukocytes have been described as mediators of
      inflammation-associated angiogenesis, the effects of direct chronic endothelial
      activation have not been addressed in this context. Using an uncleavable mutant
      of the transmembrane form of tumor necrosis factor-alpha (TNF-alpha), we have
      established models of stable TNF-alpha expression in endothelial cells in vitro
      and in transgenic mice in vivo. In the in vitro model, continuous endothelial
      activation leads to increased leukocyte cellular adhesion molecule expression and
      intracellular reactive oxygen species, hallmarks of a proinflammatory and
      dysfunctional endothelium. In addition, stable expression of TNF-alpha in
      endothelial cells increased angiogenic sprout formation in the presence but also
      in the absence of angiogenic growth factors. The partial neutralization of this
      effect by TNF-alpha antibodies and the inability of conditioned media from stable
      TNF-alpha-expressing endothelial cells to induce angiogenic activities in control
      endothelial cells suggest that this effect does not require expression of
      additional autocrine factors, but is an autonomous effect of the transmembrane
      TNF on the endothelial cells. Furthermore, using the Matrigel plug assay in vivo,
      increased angiogenesis was observed in endothelial TNF-alpha-expressing
      transgenic versus control mice. In conclusion, chronic inflammatory changes
      mediated by TNF-alpha can induce angiogenesis in vitro and in vivo, suggesting
      endothelial cell activation as a direct link between inflammation and
      angiogenesis.

PMID- 16410683
TI  - Human placental lactogen decreases regional blood flow in anesthetized pigs.
AB  - In 22 pigs anesthetized with sodium pentobarbitone, changes in blood flow caused
      by infusion of human placental lactogen into the left renal, external iliac, and
      anterior descending coronary arteries were assessed using electromagnetic
      flowmeters. In 17 pigs, infusion of human placental lactogen whilst keeping the
      heart rate and arterial pressure constant decreased coronary, renal and iliac
      flow. In 5 additional pigs, increasing the dose of human placental lactogen
      produced a dose-related decrease in regional blood flow. The mechanisms of the
      above response were studied in 15 of the 17 pigs by repeating the experiment of
      infusion. The human placental lactogen-induced decrease in regional blood flow
      was not affected by blockade of cholinergic receptors (5 pigs) or of alpha
      adrenergic receptors (5 pigs), but it was abolished by blockade of beta2
      adrenergic receptors (5 pigs). The present study showed that intra-arterial
      infusion of human placental lactogen primarily decreased coronary, renal and
      iliac blood flow. The mechanism of this response was shown to be due to the
      inhibition of a vasodilatory beta2-adrenergic receptor-mediated effect.

PMID- 16410684
TI  - The transcripts of SFRP1,CEP63 and EIF4G2 genes are frequently downregulated in
      transitional cell carcinomas of the bladder.
AB  - OBJECTIVE: The aim of the present study was to identify differentially expressed
      genes that might be associated with the phenotype of superficial and invasive
      bladder cancer. METHODS: Differential display reverse transcriptase PCR (DDRT
      PCR) was used to compare the expression pattern between normal bladder tissue and
      4 groups of transitional cell carcinomas of the bladder regarding clinical stage
      and grade. RESULTS: We were able to identify 72 different transcripts, of which
      57 (79%) showed homology to known genes, 12 (17%) to hypothetical proteins and 3
      (4%) to human expressed sequence tags. Among the differentially expressed genes,
      SFRP1,CEP63 and EIF4G2 were further validated by quantitative RT-PCR in a series
      of 50 transitional cell carcinomas. Overall, the transcripts of these three genes
      were shown to be downregulated in the bladder tumors analyzed. In accordance with
      the DDRT-PCR results, the SFRP1 transcripts were shown to be downregulated in 90%
      (45/50) of the bladder tumors as compared with the normal bladder tissue.
      Although EIF4G2 and CEP63 transcripts exhibited three different expression
      patterns, downregulation was found in about 50% of the cases analyzed. In
      addition, downregulation of both CEP63 and EIF4G2 gene transcription was
      associated with invasive tumors. CONCLUSION: The use of DDRT-PCR analysis to
      compare expression patterns among different subgroups of bladder tumors allowed
      us to identify a significant number of genes implicated in different cellular
      pathways that, when up- or downregulated, might play a role in the tumorigenic
      process of the bladder.

PMID- 16410685
TI  - Sequential treatment with exemestane and non-steroidal aromatase inhibitors in
      advanced breast cancer.
AB  - BACKGROUND: The steroidal aromatase inactivator exemestane has demonstrated
      activity after prior failure of non-steroidal aromatase inhibitors (including
      third-generation inhibitors letrozole and anastrozole) in postmenopausal women
      with advanced breast cancer. If exemestane is used as first anti-aromatase agent,
      however, it is unclear whether patients can still benefit from letrozole or
      anastrozole after progression. PATIENTS AND METHODS: Postmenopausal patients with
      advanced, hormone receptor-positive or -unknown breast cancer were eligible for
      this study. Patients with no prior exposure to anti-aromatase drugs received
      exemestane, 25 mg daily, as first anti-aromatase agent. At the time of
      progression, patients were crossed-over to anastrozole or letrozole if further
      endocrine therapy was considered appropriate. Patients with prior exposure to
      anti-aromatase agents were also included in the study, and were given anastrozole
      or letrozole if they had previously received exemestane, or exemestane if they
      had previously received anastrozole or letrozole. The primary endpoint of the
      study was the clinical benefit rate (complete response + partial response +
      stabilization of disease for >or=24 weeks). RESULTS: Forty patients received
      exemestane 25 mg daily as first anti-aromatase agent, with a CB rate of 67.5%
      (95% CI 52.9-82.0%) and a median time to progression (TTP) of 9.6 months. In 18
      patients, letrozole (n = 17) or anastrozole (n = 1) were used after failure of
      exemestane: the CB rate was 55.6% (95% CI 32.6-78.5%) with a median TTP of 9.3
      months. In 23 patients, exemestane was used after failure of letrozole or
      anastrozole: the CB rate was 43.5% (95% CI 23.2-63.7%) with a median TTP of 5.1
      months. CONCLUSIONS: Our study confirms that exemestane is active after prior
      failure of letrozole or anastrozole. We have also shown that patients can receive
      exemestane as their first anti-aromatase agent and still benefit from letrozole
      or anastrozole after progression. This suggests that the partial non-cross
      resistance between steroidal and non-steroidal anti-aromatase agents is
      independent of the sequence employed.

PMID- 16410686
TI  - Prognostic relevance of basal cytokeratin expression in operable breast cancer.
AB  - OBJECTIVE: We investigated whether basal cytokeratin (CK5/6 or CK17) expression
      had an impact on survival in patients with operable breast cancer. METHODS:
      Expression of CK5/6 or CK17 was analyzed by immunohistochemistry in 195 women
      with breast cancer. RESULTS: In total, 72 (37%) tumor samples were regarded as
      being positive for CK5/6 or CK17. The basal-like phenotype as defined by basal
      cytokeratin expression, lack of estrogen receptor (ER) and absence of HER2
      overexpression was found in 48 (25%) cases. Positive staining for CK5/6 or CK17
      was associated with worse prognosis when compared with patients negative for
      basal cytokeratins in all cases (5-year cancer-specific survival rate 59.4 vs.
      77.5%, p = 0.0273) and in the node-negative group (70.5 vs. 90.8%, p = 0.0208)
      but not in the node-positive group (43.9 vs. 65.4%, p = 0.1182). To determine the
      real prognostic value of basal cytokeratins, survival in a group of ER-negative
      patients was analyzed depending on CK5/6 or CK 17 expression. No influence on
      survival was observed. The outcome of patients whose cancers were positive for
      cyclin E regardless of ER status was not changed by CK5/6 or CK17 expression. In
      multivariate analysis, independent prognostic factors affecting survival in the
      whole group included: nodal involvement, HER2 status and cyclin E expression.
      Neither ER status nor basal cytokeratin expression retained statistical
      significance. CONCLUSION: We demonstrated that the poor prognosis associated with
      the basal-like phenotype of breast cancer was determined by ER absence and cyclin
      E expression and not by CK5/6 or CK17 expression.

PMID- 16410687
TI  - Dysplasia and cancer in ulcerative colitis: too many questions, too few answers.

PMID- 16410688
TI  - Prevention of colorectal cancer in inflammatory bowel disease: value of screening
      and 5-aminosalicylates.
AB  - Colorectal cancer is a serious complication of inflammatory bowel disease. Given
      this fact, it is necessary to examine the opportunities for current and future
      approaches to colorectal cancer prevention. The value of surveillance colonoscopy
      and chemoprevention of colorectal cancer with 5'-aminosalicylic acid has been
      evaluated in the recent literature. The current state of knowledge in the
      epidemiology of and new approaches to the prevention of cancer and dysplasia in
      inflammatory bowel disease were reviewed. It is concluded that there is
      significant preclinical and clinical evidence to suggest that 5-aminosalicylate
      drugs reduce the risk of colorectal neoplasia. However, the minimal dosage to
      achieve this chemopreventive effect remains unclear. There is also indirect
      evidence to suggest that surveillance colonoscopy is beneficial for patients with
      inflammatory bowel disease, particularly in those with long-standing pancolitis
      or primary sclerosing cholangitis-associated inflammatory bowel disease. However,
      definitive proof from prospective clinical trials is not available.

PMID- 16410689
TI  - [Gene expression profiling for prediction of response to chemotherapy].
AB  - Numerous genes whose expression is controlled by complex regulatory networks are
      involved in the development and progression of each cancer,and those genes will
      be the key factors for determining each characteristic of the tumor. The recent
      development of DNA microarray and related technologies provides an opportunity to
      perform more detailed characterization( profiling) of individual tumor cells.
      Indeed, the gene expression profile of a tumor provides a unique molecular
      portrait or signature that can be correlated with clinical behavior and drug
      responsiveness. The development of personalized( or customized) medicine and
      molecularly targeted drugs is enthusiastically awaited based on the results of
      research examining genomic diversity such as SNPs( single nucleotide
      polymorphisms), gene expression profiling with DNA microarrays, and analysis of
      protein expression and interactions.

PMID- 16410690
TI  - [Approaches to anemia, thrombocytopenia, and DIC in cancer patients].
AB  - Patients with cancer-related anemia have an inadequate Epo response that is
      further impaired by cancer treatments such as chemotherapy. Significant number of
      studies have demonstrated that treatment of anemia in cancer patients using
      recombinant human EPO(rHuEPO, epoetin alfa) significantly increases
      hemoglobin(Hb) levels,reduces transfusion requirements,and improves quality of
      life,particularly by relieving fatigue. However,the findings of several studies
      have raised the possibility of an adverse effect of thromboembolism. The American
      Society of Clinical Oncology and the American Society of Hematology developed an
      evidence-based clinical practice guideline for the use of epoetin in patients
      with cancer. In cancer patients, the risk of bleeding depends not only on the
      platelet count, but also on the underlying disease, in accordance with
      coagulation defects. The cause of thrombocytopenia must be established prior to
      platelet transfusion since platelet transfusions may be relatively
      contraindicated in certain conditions e. g., heparin-induced
      thrombocytopenia(HIT), and thrombotic thrombocytopenic purpura/hemolytic uremic
      syndrome(TTP/HUS).

PMID- 16410692
TI  - [Principles of managing chemotherapy-induced nausea and vomiting].
AB  - Chemotherapy-induced nausea and vomiting (emesis) can significantly affect a
      patient's quality of life, leading to poor compliance with further chemotherapy
      treatment. For patients treated with emetogenic chemotherapy, it is very
      important to prevent nausea and vomiting completely. The incidence and severity
      of nausea and/or vomiting in patients receiving chemotherapy are affected by
      numerous factors, including: 1) the specific chemotherapeutic agents used; 2)
      their dosage; 3) the schedule and route of administration; and 4) individual
      patient variability. Approximately 70 to 80% of all cancer patients receiving
      chemotherapy experience emesis, whereas 10% to 44% experience anticipatory
      emesis. The following general principles are recommended. 1) A 5-HT3 receptor
      antagonist should be administered prior to each day's 1st dose of moderately or
      highly emetogenic chemotherapy. 2) Dexamethasone should be administered once
      daily either orally or intravenously for every day of moderately or highly
      emetogenic chemotherapy and for 2-3 days after chemotherapy for regimens that are
      likely to cause significant delayed-emesis. 3) The most effective way to treat
      anticipatory nausea and/or vomiting is to prevent it by using optimal antiemetic
      therapy during every cycle of treatment.

PMID- 16410691
TI  - [Management of febrile neutropenic patients].
AB  - Infection is the most common complication of febrile neutropenia. Bacterial
      infections predominate during the early stages of a neutropenic episode,whereas
      invasive fungal infections tend to occur later. Prompt initiation of
      antimicrobial agents remains the gold standard. The recent cumulative data
      indicate a low-risk group that is unlikely to progress to a grave clinical
      condition. In the Japanese guideline updated in 2003, the patients at low risk of
      complications are determined initially, and the patients at low risk can receive
      oral fluoroquinolones with or without amoxicillin/clavulanate. A high-risk group,
      however,must be given vigorous parenteral treatment with 4 th-generation
      cephalosporins or carbapenems with or without an aminoglycoside. Initial
      empirical therapy should be based on local epidemiology and drug-susceptibility
      patterns. Antimicrobial coverage against Pseudomonas species is necessary. If
      defervescence occurs in 3-5 days or fever persists with a stable condition, the
      same agents could be continued. If fever persists with no improvement in
      conditions, an aminoglycoside is added to patients on monotherapy as an initial
      therapy. Changing the Beta-lactams is considered for patients on combination
      therapy with Beta-lactams plus an aminoglycoside. Fungal cultures and serological
      test are performed. After 48 hours of observation on the treatment, antifungals
      are then started depending on the results of culture and serological tests.
      Chemoprophylaxis should be considered for patients at high risk.

PMID- 16410693
TI  - [Management of chemotherapy-induced mucositis and diarrhea].
AB  - Mucositis is a common complication of cytoreductive cancer chemotherapy.
      Stomatitis is associated with a higher risk of bacterial infection and treatment
      related death. Basic oral care is recommended to reduce the incidence and
      severity of stomatitis. Recently, new effective prophylaxis against stomatitis
      has been developed such as human keratinocyte growth factor and AES-14. Gastritis
      can sometimes cause severe bleeding,and it may be life-threatening. It has been
      shown that prophylactic H2 blockers or proton pump inhibitors can reduce the
      incidence and severity of gastric mucosal injury. The risk for chemotherapy
      induced diarrhea is significantly greater for chemotherapeutic regimens that
      contain irinotecan. Intestinal alkalization and Hangeshasin-to a Chinese herbal
      product are applied in clinical practice in Japan to prevent or reduce irinotecan
      induced diarrhea,but careful monitoring,early detection and rapid cure are most
      important to prevent treatment-related death.

PMID- 16410694
TI  - [Neurotoxicity and dermatologic toxicity of cancer chemotherapy].
AB  - Neurological dysfunction is a common adverse effect of many chemotherapeutic
      agents. Any part of the peripheral or central nervous system can be affected.
      Various clinical syndromes including encephalopathy, cerebellar syndrome, cranial
      neuropathy, seizure,myelopathy, and peripheral neuropathy commonly occur. In
      several drugs, neurotoxicity is a dose-limiting toxicity. Multiple factors such
      as cumulative dose, route of administration, drug metabolism and synergistic
      effects of other drugs or radiotherapy impact the incidence and severity of
      neurotoxicity. Much of the research in chemotherapy-induced neuropathies has been
      focused on the goal of ameliorating or preventing the neurotoxicity without
      altering the effectiveness of the medication. Various dermatologic complications
      of cancer chemotherapy such as extravasation, hyperpigmentation, nail change,
      radiation recall reaction and hypersensitivity reaction can occur. In
      extravasation, many cytotoxic agents are irritants or non-vesicants, however,a
      significant number of commonly used drugs are classified as vesicants, including
      the vinca alkaloids anthracyclines and taxanes. Extravasation of vesicant drugs
      into the subcutaneous tissue results in severe local pain and ulceration with
      progressive tissue destruction. Strategies to reduce the incidence of
      extravasation and minimize its associated morbidity are crucial to quality of
      life for cancer patients. The more common clinical features of chemotherapy
      induced neurologic and dermatologic toxicities are discussed below.

PMID- 16410695
TI  - [Fatigue, anxiety and depression and their management].
AB  - Sickness behaviors such as fatigue, anxiety and depression play an important role
      in the body's defense mechanism. However, once these symptoms become chronic,
      they are harmful to patients with cancer by decreasing the immune reaction or
      exacerbating pain and other symptoms. It should be recalled that both medical and
      surgical interventions profoundly influence fatigue, anxiety and depression of
      cancer patients. Since latent fatigue, anxiety and depression may be overlooked
      behind somatic symptoms, communication skills are necessary to understand the
      suffering of patients. Routine assessment of these symptoms are essential for
      early intervention in the care of cancer patients. Communication skills such as
      careful listening and counselling are also useful methods in caring for patients
      with these symptoms. Although non-medical intervention is usually effective for
      these symptoms of fatigue, anxiety and depression, approximately 10 to 15% of
      patients require specific treatment by a psychiatrist. Above all, fatigue,
      anxiety and depression should be treated as part of the total pain experienced by
      cancer patients.

PMID- 16410696
TI  - [Pilot study of primary systemic chemotherapy with docetaxel (DOC), epirubicin
      (EPI) and capecitabine (Xeloda) in patients with advanced breast cancer].
AB  - We evaluated the safety and efficacy of primary systemic chemotherapy (PSC) with
      docetaxel (DOC), epirubicin (EPI) and capecitabine (Xeloda:XLD) in 10 patients
      with advanced breast cancer. Their mean age was 54.7 years,and preoperative
      stages were IIB, seven cases; IIIA, two; and IV, one,respectively. The regimen
      consisted of XLD (2,400 or 3,000 mg/day) orally for 14 consecutive days, and DOC
      (60 or 70 mg/m2) and EPI (50 or 60 mg/m2) intravenously on day 8. This was
      repeated 4 times every 3 weeks. One patient discontinued this regimen after one
      course at her own request. Although the results revealed leucopenia and
      neutropenia of more than grade 3 in 8 and 10 patients,they could be treated on an
      outpatient basis with the use of G-CSF to maintain this regimen. Alopecia of
      grade 2 was found in all patients,neutropenic fever of more than 38.5 degrees C
      in 5,and hand-foot syndrome in 3. Downstaging after PSC was demonstrated in 7
      cases (Stage IIB to I, three cases; IIB to IIA, three; and III A to I, one), with
      a response rate of 77.8%. Breast conserving therapy was performed in 8/10
      patients. Pathological findings on cytological degeneration showed grade 0, one;
      grade 1a,seven; grade 2, one; and grade 3, one, respectively. Axillary lymph node
      metastasis was revealed in 7 cases. This regimen would be an alternative to PSC
      on an outpatient basis while taking great care of myelosuppression and hand-foot
      syndrome.

PMID- 16410697
TI  - [A phase I study of combination chemotherapy using TS-1 and weekly paclitaxel for
      advanced gastric cancer].
AB  - The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment
      of unresectable and recurrent gastric cancer was evaluated in this study.
      Paclitaxel was administered by intravenous drip infusion at a starting dose
      (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a
      dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A
      total of 9 patients were enrolled in this study. Two out of 6 patients treated
      with level 1 suffered from leukocytopenia and neutropenia, which were determined
      as dose-limiting toxicity (DLT). Three patients were treated with level 2, in
      which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients
      suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia,
      eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According
      to these results,level 1 of this regimen was recommended as a safe treatment for
      gastric cancer patients. A phase II study will be performed to evaluate the
      efficacy of the combination chemotherapy.

PMID- 16410698
TI  - [Clinical administration of oxaliplatin for patients previously treated for
      refractory advanced or recurrent colorectal cancer].
AB  - Oxaliplatin (L-OHP) was administered to 10 patients previously treated for
      refractory advanced or recurrent colorectal cancer. The number of times each had
      received previous chemotherapy treatment ranged from 1 to 5 (median 3) for
      durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet
      approved for sale in Japan, and could only be imported from overseas for personal
      use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body.
      Combinations with 5-FU were administered differently from previous regimens;
      these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was
      administered from 1 to 14 times (median 4.5), and the response to treatment was
      PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there
      was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had
      to be suspended because of their financial situations. Overall survival from
      commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and
      after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events
      included bone marrow suppression in three patients, 3 cases of leukocytopenia
      (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one
      patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two
      patients. All reactions were able to be controlled except for one patient with
      Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy
      can possibly contribute to prolongation of survival time in cases of refractory
      advanced colorectal cancer. It is useful to combine L-OHP with high-dose
      continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most
      useful of the FOLFOX regimens because it is simple and can be administered on an
      outpatient basis.

PMID- 16410699
TI  - [Example of safety measures for antineoplastic agents immediately after market
      launch--a case of TS-1 capsule all example use result investigation that executes
      safety monitoring--].
AB  - As a measure to ensure safe use of TS-1 during the early marketing period, a drug
      use investigation was conducted on an all-case basis. Extra safety
      monitoring,rarely included in the use investigation,was also planned for patients
      who began therapy with this agent. Of the 4,177 subjects registered during the
      year beginning in March 1999, 3,882 started TS-1 therapy. Aside from 74 dropouts,
      3,808 cases were evaluable for safety. The overall incidence of adverse
      reactions, with high frequencies of myelosuppression and gastrointestinal
      disorders, was 74.3%: a result similar to an incidence of 77.5% (100/129) found
      in the early phase II trial with gastric cancer patients. Safety monitoring made
      it possible to check if a given patients was eligible for proper use before
      treatment is begun. During TS-1 administration,collaboration was formed between
      physicians and medical representatives to ensure regular laboratory testing and
      to check the test findings. Measures were considered necessary to secure the safe
      use of drugs with manifest risk of serious adverse reactions, such as
      antineoplastic agents, during the initial period of market introduction. Our
      present approach proved effective as one of such measures.

PMID- 16410700
TI  - [A 65-year-old man with liver metastases after lung cancer resection that
      responded to concomitant use of gemcitabine and carboplatin].
AB  - A 65-year-old male with liver metastases after lung cancer resection was treated
      with five courses of chemotherapy consisting of gemcitabine (GEM) 1,000 mg/m2
      (day 1, 8, every 4 weeks) plus carboplatin (CBDCA) AUC 6 (day 1, every 4 weeks).
      A partial response (PR) was achieved, his symptoms abated and his quality of
      life(QOL) improved. Although bone marrow suppression was observed as a side
      effect, it was within the tolerable range and did not interfere with therapy.
      This approach may be worth considering as a first-line anti-cancer chemotherapy
      for recurrence lung cancer.

PMID- 16410701
TI  - [Two cases of malignant lymphoma with high fever and C-reactive protein (CRP)
      elevation after treatment with granulocyte colony-stimulating factor (G-CSF)].
AB  - We present two cases of malignant lymphoma that developed a high fever that
      eventually reached an extremely high 38.9 degrees C. The C-reactive protein( CRP)
      elevation also climbed to a very high 12.2 mg/dl after treatment with granulocyte
      colony-stimulating factor (G-CSF). In the one case, after stem cells were
      mobilized with CHASER therapy (cyclophosphamide, cytarabine, etoposide,
      dexamethasone and rituximab) followed by G-CSF (filgrastim 600 microg/day)
      subcutaneous daily, the serum CRP level rose to a maximum of 5.6 mg/dl, with a
      maximum fever elevation of 38.9 degrees C. In the other case, after the subject
      was given CHASE therapy followed by subcutaneous treatment with G-CSF (filgrastim
      75 microg/day) daily, the maximum serum CRP level was 12.2 mg/dl along with a
      maximum fever of 38.9 degrees C. Although no infection was found in either case,
      multiple antibacterial agents were ineffective;after discontinuation of G-CSF,
      fever dissipated and the serum CRP level became negative. G-CSF induces the
      proliferation and differentiation of neutrophils and also causes the mobilization
      of mature neutrophils from hematopoietic tissues. With the increasing propensity
      to G-CSF, we must keep in mind the possibility of such adverse reactions so as to
      serve the overall best interests of the patient.

PMID- 16410702
TI  - [A case of thymic cancer with pericardial tamponade as initial manifestation].
AB  - We report a case of thymic cancer with pericardial tamponade in a 70-year-old
      woman. The patient complained of chest pain and was carried to our hospital. CT
      scan showed a mediastinal mass and massive pericardial effusion. The effusion was
      serous fluid, not bloody, and no malignant cells were found. The patient
      underwent a tumor resection, and the final pathological diagnosis was squamous
      cell carcinoma of the thymus. In a review of 14 cases of thymic tumor with
      pericardial tamponade as initial manifestations in the Japanese literature,there
      were only three cases of thymic cancer. The prognosis was reported to be
      extremely poor.Some reports showed the effectiveness of chemotherapy and
      irradiation therapy. We should keep looking for the best treatment for this
      disease.

PMID- 16410703
TI  - [A case of successful treatment by low-dose 5-fluorouracil and cisplatin for
      liver metastases of esophageal adenosquamous carcinoma].
AB  - Adenosquamous carcinoma of the esophagus is an uncommon type of esophageal tumor.
      In the present case, a 54-year-old man without symptoms was diagnosed with
      esophageal squamous cell carcinoma, based on endoscopic examination of a biopsy
      specimen. Endoscopy and barium roentgenography revealed a superficial plateau
      type lesion, 2 cm in length, in the lower esophagus. Esophagectomy with
      lymphadenectomy was performed via a right thoraco-abdominal approach. The
      histological diagnosis was adenosquamous carcinoma with no lymph node metastasis.
      Three years after the surgery, multiple liver metastases were detected by
      computed tomography. The patient was treated with a combination of low-dose 5
      fluorouracil(350 mg/body/day) and low-dose cisplatin (7 mg/body/day). Because the
      first course of chemotherapy was very effective and the number of liver
      metastases was reduced,a further 6 courses were administered. After 6 courses of
      chemotherapy, no liver metastases were detected. Based on the present findings,
      we recommend low-dose 5-fluorouracil/cisplatin therapy for liver metastasis from
      esophageal adenosquamous carcinoma.

PMID- 16410704
TI  - [Two cases of advanced gastric cancer with peritoneal dissemination acquired long
      term response three years or more by postoperative treatment with oral anticancer
      drug TS-1].
AB  - The first patient is a 60-year-old man who underwent total gastrectomy and
      splenectomy for type-3 gastric cancer after neoadjuvant chemotherapy. The second
      patient is a 69-year-old woman who underwent distal gastrectomy for type-2
      gastric cancer and pyloric stenosis after neoadjuvant chemotherapy. Some
      peritoneal dissemination was observed in these two cases. No re-growth of
      peritoneal dissemination was seen for three years or more from treatment with the
      oral anticancer drug TS-1. Treatment on an outpatient basis, therefore, greatly
      contributed to their quality of life. We consider TS-1 as a first-line anti
      cancer drug for advanced gastric cancer.

PMID- 16410705
TI  - [Stenting and radiotherapy for malignant tracheal stenosis due to mediastinal
      lymph node recurrence from gastric cancer--a case report].
AB  - The case is a 74-year-old woman,who underwent curative resection six years
      earlier for stomach cancer in the cardia extending to the esophagus (Stage IIIA).
      She noticed hoarseness and cough in September 2004, and CT revealed lymph node
      metastasis of the cancer in the upper mediastinum. The tumor pressured the SVC,
      the esophagus,and especially the trachea that narrowed up to a diameter of 5 mm.
      To secure the air way, first, a self-expandable metallic stent was placed in the
      narrowed trachea under general anesthesia. Irradiation to the upper mediastinal
      tumor was further applied for a total of 46 Gy from October to November, 2004.
      Symptom relief was obtained over the course by a marked reduction in the size of
      the metastatic tumor, and the disease remained stable for 5 months. In general,a
      stomach cancer that is mostly adenocarcinoma has been recognized to have low
      receptivity for radiotherapy. Nevertheless,this case suggests that radiotherapy
      can play an important role in local control and symptom relief for symptomatic
      stomach cancer patients.

PMID- 16410706
TI  - [Three advanced gastric cancer cases with liver metastases successfully treated
      by TS-1/CDDP combination therapy].
AB  - Three cases with unresectable advanced gastric cancer with liver metastases were
      successfully treated by the combination therapy of TS-1 and cisplatin( CDDP). TS
      1 (1.25 m2>: 80 mg/day, 1.25 m2-1.50 m2: 100 mg/day, > or =1.50 m2: 120 mg/day)
      was administered orally for 14 consecutive days followed by 14 days rest,and a 24
      h infusion of CDDP (70 mg/m2) was administered on day 8 of each course. Treatment
      was repeated every 4 weeks unless disease progression was observed. Partial
      response was obtained in all of the following three advanced gastric cancer cases
      with liver metastases. Case 1: 67-year-old male with Borrmann type I gastric
      cancer with multiple liver metastases. Case 2: 55-year-old female with multiple
      liver and lymph node metastases whose primary gastric lesion was surgically
      resected. Case 3: 53-year-old-male with Borrmann type III gastric cancer with
      liver and lymph node metastases. TS-1/CDDP therapy can be highly recommended for
      the treatment of advanced gastric cancer with liver metastases.

PMID- 16410707
TI  - [A case of gastric adenosquamous carcinoma with abdominal paraaortic lymph node
      metastases successfully treated by TS-1 plus CDDP neoadjuvant chemotherapy].
AB  - A 62-year-old woman was admitted for anemia. An endoscopic examination revealed
      type 2 cancer from the upper body of the stomach to the antrum, and abdominal CT
      scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative
      diagnosis was cStage IV gastric cancer (cT 3, cN 3, cH 0, cP 0, cM 0). Since a
      curative operation was deemed impossible, we conducted neoadjuvant chemotherapy
      using TS-1 plus cisplatin (CDDP) for downstaging. TS-1( 100 mg/day) was orally
      administered for 3 weeks,and CDDP (60 mg/m2) was given intravenously on day 8.
      Appetite loss of grade 3 and erythropenia of grade 1 were observed. After two
      courses of chemotherapy the primary lesion and the paraaortic lymph nodes were
      significantly reduced in size. She was judged as clinical PR, followed by distal
      gastrectomy and lymph node dissection, resulting in curability A.
      Histopathologically, the tumor was diagnosed as adenosquamous carcinoma of the
      stomach with lymph node metastasis at only No.3. This case suggests that
      neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric
      adenosquamous carcinoma with massive lymph node metastases.

PMID- 16410708
TI  - [Low-dose weekly paclitaxel therapy proved useful for a case of recurrent gastric
      cancer with clinically latent hepatic cirrhosis].
AB  - The patient was a 68-year-old-man who suffered from recurrent peritoneal gastric
      cancer. He was initially treated with TS-1 as an outpatient. However, his serum
      CEA level elevated in March 2004, and he complained of epigastric pain in June. A
      chest and abdominal CT revealed lung and local recurrence. He began weekly
      paclitaxel as second-line chemotherapy in September. Paclitaxel was infused once
      a week for two weeks as one cycle, at a dose of 60 mg because of the clinically
      latent hepatic cirrhosis. One month after the first infusion therapy, epigastric
      pain was greatly reduced. A CT scan showed the lung metastasis had disappeared
      and the size of the tumor around the anastomosis was reduced to 50% after 2
      months. The toxic events were appetite loss (grade 2) and alopecia (grade 2).

PMID- 16410709
TI  - [A case report of poorly-differentiated adenocarcinoma in sigmoid colon cancer
      with liver and pulmonary metastasis responding to TS-1 and CPT-11].
AB  - A 66-year-old woman (156 cm, 58 kg) underwent sigmoid colectomy for cancer. She
      was found to have simultaneous liver and peritoneal metastases at operation,
      which had not been detected with CT examination before operation. After
      operation, CT showed multiple liver metastasis and a high level of CEA and CA19-9
      . Pathological findings were type 3, 30 x 20 mm, poorly-differentiated
      adenocarcinoma, se, ly 2, v 2, n 2 (+), ow (-), aw(-), H 3, P 0 (stage IV).
      Treatment of the patient consisted of daily oral administration of 80 mg TS-1 for
      21 days and 60 mg CPT-11 on 1 day and 15 day as one course. After 2 courses,
      tumor sizes of liver metastases and the level of tumor markers became reduced.
      The current case suggested that the administration of TS-1 and CPT-11 may have a
      potent therapeutic efficacy in advanced colorectal cancer.

PMID- 16410710
TI  - [Liver metastasis from sigmoid colon cancer with peritoneal dissemination showed
      a complete response to TS-1].
AB  - A 64-year-old man with unresectable sigmoid adenocarcinoma due to peritoneal
      dissemination (P3) and liver metastasis (H2) treated with TS-1, showed a complete
      response. TS-1 is an oral anticancer drug that produces biochemical modulation.
      It is composed of tegafur, gimestat and ostat potassium in a molar ratio of
      1:0.4:1 to increase the effect of 5-FU and to decrease toxicity in the digestive
      canal. Treatment with TS-1 requires no hospitalization and can enhance the
      quality of life of the patient. TS-1 is expected to be an effective agent for the
      treatment of colon cancer with liver metastasis and peritoneal dissemination.

PMID- 16410711
TI  - [A case of advanced rectal cancer responding to l-Leucovorin (LV)/5-fluorouracil(
      5-FU) therapy as neoadjuvant chemotherapy].
AB  - We report a case in which l-Leucovorin/5-fluorouracil (l-LV/5-FU) therapy was
      remarkably effective for advanced rectal cancer as neoadjuvant chemotherapy
      (NAC). A 54-year-old man complained of bloody stool and constipation,and was
      diagnosed as having stage IIIB advanced rectal cancer with N2 lymphnode
      metastases on July 31, 2003. Two cycles of NAC by l-LV/5-FU therapy were
      performed. On abdominal computed tomography (micro CT), the primary lesion in the
      rectum decreased 82% and the metastatic lymphnodes had disappeared. As we
      established a diagnosis of the downstaging for stage II, a lower anterior
      resection with D3 lymphnode dissection was performed on December 5, 2003. The
      pathological examination demonstrated II, mod, 1.8 x 2.2 cm, a1, ly1,v0, ow(-),
      aw(-), n0, stage II. We could allow curability-A resection. The pathological
      effect of chemotherapy was grade 2 in which cancer cells became necrotic,
      suggesting apoptosis. The postoperative course was good. Postoperatively, 3
      cycles of l-LV/5-FU therapy were performed. Although the patient had to be
      followed with internal use of 5-FU 200 mg/day as an outpatient from June 2, 2004,
      to date, there has been no sign of recurrence during the 12-month follow-up after
      the operation. Moreover, no adverse by chemotherapy was seen during the
      treatment. Thus, NAC by this therapy may be useful for patients with advanced
      rectal cancer.

PMID- 16410712
TI  - [A case of drug-induced interstitial pneumonitis after gemcitabine treatment for
      advanced pancreatic cancer].
AB  - A 54-year-old woman with advanced pancreatic cancer with peritoneal dissemination
      was given gemcitabine on days 1,8 and 15, and this was repeated on day 29 at a
      dose of 1,000-1, 150 mg/m2. After 5 courses,the total infusion was 20,900 mg.
      Thirteen days after the last infusion, she suffered from sudden dyspnea, and soon
      went into respiratory failure of WHO grade 4 with severe hypoxemia. Chest
      radiograph and CT showed interstitial infiltrates of bilateral lower lung. She
      was diagnosed with drug-induced interstitial pneumonitis due to gemcitabine.
      Corticosteroid therapy consisting of methylprednisolone (1 g/day) for three days
      followed by prednisolone(50 mg/day) was significantly effective in treatment of
      respiratory failure. Her symptoms were improved clinically within one week after
      the onset,and the interstitial shadows in the lungs had almost disappeared
      radiographically within three weeks after the onset. Respiratory symptoms did not
      appear again,but the patient died of progression of peritoneal dissemination of
      pancreatic cancer 73 days after the onset of the interstitial pneumonitis.
      Gemcitabine- induced interstitial pneumonitis is very rare, but could become a
      serious complication in long-term gemcitabine treatment.

PMID- 16410713
TI  - [A case of liver metastasis successfully treated with S-1 monotherapy in the
      patient with recurrent breast cancer].
AB  - We experienced a case of recurrent breast cancer resistant to prior medications,
      which was treated with oral S-1, a fluoropyrimidine-class anticancer drug, and
      exhibited the marked shrinkage of liver metastasis. The prior treatments
      including anthracycline and taxane were judged not effective because of the
      progressive disease. Then the oral treatment with S-1 was started at 120 mg/day
      bid. targeting metastatic lesions of the liver. At the end of the second cycle,a
      significant improvement was noted with a decrease rate of 82.5%. The S-1
      monotherapy was thus considered to be an effective treatment for advanced or
      recurrent breast cancer resistant to anthracyclines and taxanes.

PMID- 16410714
TI  - [Two patients effectively treated with S-1 therapy for liver metastasis of breast
      cancer resistant to other anticancer drugs].
AB  - We had 2 patients with marked shrinkage of liver metastasis by administration of
      the oral fluorinated pyrimidine anticancer drug S-1 for advanced/recurrent breast
      cancer that was resistant to taxane and another antitumor drugs. Both patients
      almost completed the full dose through the whole course of treatment,and the drug
      showed good tolerability. S-1 was considered to possess beneficial antitumor
      efficacy and tolerability and to be promising as home chemotherapy for
      advanced/recurrent breast cancer.

PMID- 16410715
TI  - [Successful monotherapy with S-1 in three cases of recurrent/advanced breast
      cancer non-responsive to anthracycline and taxane anticancer drugs].
AB  - We had 3 patients with recurrent/advanced breast cancer in whom a notable
      reduction in the size of the targeted tumors was seen following administration of
      S-1 (TS-1), a new oral pyrimidine fluoride anticancer drug. All of the patients
      had received taxane and/or anthracycline anticancer drugs as prior therapy;
      however, they were judged to be non-responsive to the drugs. The size of the
      targeted tumor decreased to 55.7% after 3 courses of the therapy in Patient 1.
      The tumor disappeared at completion of the third course in Patient 2, although
      the therapy was temporarily suspended during the second course due to adverse
      drug reactions, and the therapy was then resumed after 2-week drug withdrawal.
      Patient 3 was able to undergo long-term therapy, consisting of 8 courses for 11
      months, and the size of the tumor reduced to 58.1%. No serious adverse drug
      reactions to S-1 occurred in our 3 patients. It is thought that less toxicity
      enabled Patient 3 to undergo long-term therapy. We consider S-1 to be a useful
      anticancer drug for treatment of taxane and/or anthracycline resistant recurrent
      breast cancer.

PMID- 16410716
TI  - Capitalizing on AKT signaling to inhibit hepatocellular carcinoma cell
      proliferation.

PMID- 16410717
TI  - Detection of BRAF gene mutation in primary choroidal melanoma tissue.
AB  - Numerous BRAF mutations have been detected in melanoma biopsy specimens and cell
      lines. In contrast, several studies report lack of BRAF mutations in uveal
      melanoma including primary and metastatic choroidal and ciliary body melanomas.
      To our knowledge, for the first time, here we report a case of choroidal melanoma
      harboring the BRAF mutation (V600E). The activation of RAF/MEK/ERK pathway,
      although independent of BRAF mutation, was reported in uveal melanoma. The
      presence of V600E mutation indicates that the RAF/MEK/ERK pathway, in addition to
      cutaneous melanoma progression, may play a role in the choroidal melanoma
      development.

PMID- 16410718
TI  - Cancer-selective therapy of the future: apoptin and its mechanism of action.
AB  - Classical chemotherapy, that specifically targets rapidly proliferating cells,
      has been in existence for over eighty years and has proven to be fully successful
      in only a limited number of cancers. Thus, this review focuses on a novel,
      emerging approach for cancer therapy that uses alternative, and more unique
      features of cancer cells. This new approach facilitates the selective targeting
      of cancer, while sparing normal, non-transformed cells. Examples of molecules
      that kill cancer cells selectively are: apoptin, E4orf4, viral protein R (VpR),
      and Brevinin-2R. Below we focus on apoptin, a product of the third open reading
      frame (VP3) of the chicken anemia virus. Besides discussing apoptin's mechanism
      of action, we also provide concise insight into the biology of a chicken anemia
      virus infection. Since apoptin's cancer-selective toxicity depends on its nuclear
      localization, we broadly discuss mechanism(s) involved in its nuclear retention
      (both nuclear import and export). We also discuss recent findings on apoptin's
      molecular mechanism of action, with a focus on the role of Nur77 in apoptin's
      nucleo-cytoplasmic signaling. Finally, we compare the current findings on apoptin
      to the mechanism of cancer selective toxicity of E4orf4. In the 'summary' 
      section, besides highlighting important issues related to cancer-selective
      therapy, we also discuss concurrent approaches towards therapy personalization,
      particularly those related to the in vivo-, and real time cancer-therapy efficacy
      monitoring, using "lab-on-the-chip" and other emerging technologies.

PMID- 16410719
TI  - p14ARF directly interacts with Myc through the Myc BoxII domain.
AB  - Myc is a well known proto-oncogene encoding for a transcription factor whose
      activity is tightly regulated in the cellular context. Myc was the first oncogene
      recognized to activate the ARF tumor suppressor gene which suppresses cell
      proliferation partly through stabilization of the p53 tumor suppressor protein
      but which also has p53-independent growth-suppressive functions. Recent studies
      have indicated that mouse p19ARF negatively regulates Myc's transcriptional
      activity. We here show that the human p14ARF directly associates with Myc and
      relocates Myc from the nucleoplasm to the nucleolus. We found that p14ARF
      interacts with the Myc-Max complex and the binding of p14ARF does not interfere
      with Myc-Max interaction in vitro. Protein interaction assays define the Myc
      BoxII as a critical domain required for interaction with p14ARF. Moreover, we
      identify 30 amino acids encompassing Myc BoxII domain required for p14ARF
      interaction and colocalization in vivo. Finally, we show that p14ARF down
      regulates Myc activated transcription and that this activity cannot be addressed
      to an intrinsic p14ARF repressor domain.

PMID- 16410720
TI  - Klotho, the long sought-after elixir and a novel tumor suppressor?

PMID- 16410721
TI  - CIAPIN1 confers multidrug resistance by upregulating the expression of MDR-1 and
      MRP-1 in gastric cancer cells.
AB  - In a previous study, we observed that cytokine-induced apoptosis inhibitor 1
      (CIAPIN1), a newly identified apoptosis inhibitor, was upregulated at the mRNA
      level in a multidrug-resistant gastric cancer cell line SGC7901/VCR. The aim of
      this study was to explore the role of CIAPIN1 in the development of multidrug
      resistance (MDR) in gastric cancer cells. Upregulation of CIAPIN1 in MDR gastric
      cancer cells was confirmed by semiquantitative RT-PCR and Western blotting. Using
      cDNA transfection and RNA interference, we successfully established stable
      transfectants with upregulation (i.e., SGC7901-pCIAPIN1) or downregulation (i.e.,
      SGC7901-pSiCIAPIN1 and SGC7901/ADR-pSiCIAPIN1) of CIAPIN1 expression,
      respectively. In vitro drug sensitivity assay demonstrated that overexpression of
      CIAPIN1 conferred MDR in SGC7901 cells whereas downregulation of CIAPIN1
      sensitized SGC7901 and SGC7901/ADR cells to anticancer drugs. CIAPIN1 protected
      both SGC7901 and SGC7901/ADR cells from ADR-induced apoptosis and reduced
      intracellular accumulation and retention of adriamycin. Moreover, expression of P
      glycoprotein (P-gp or MDR-1, a product of MDR-1 gene) and MDR-related protein-1
      (MRP-1) was upregulated by CIAPIN1. In addition, Western blotting revealed that
      CIAPIN1 decreased the expression of Bcl-2, Bax and p53. Therefore, it is
      concluded that CIAPIN1 confers MDR in gastric cancer cells, likely by
      upregulating MDR-1 and MRP-1.

PMID- 16410723
TI  - Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression
      in human breast cancer.
AB  - Expression of Secreted frizzled related protein 1 (SFRP1), a recently identified
      tumor suppressor gene encoding a WNT signaling antagonist, has been found to be
      frequently down-regulated in breast cancer and is associated with disease
      progression and poor prognosis. Here, we investigated the role of epigenetic
      silencing of SFRP1 in breast cancer cell lines and primary breast tumors. Through
      analyses by methylation-specific PCR and bisulfite sequencing, promoter
      methylation of SFRP1 was detected in 88% (7/8) of breast cancer cell lines, 17%
      (1/6) of grade 1 of ductal carcinoma in situ (DCIS), 69% (9/13) of grade 2 and 3
      of DCIS, 68% (19/28) of invasive ductal carcinomas (IDC) and 33% (6/18) of
      lobular carcinomas but not in any (0/14) of normal mammoplasty specimens and
      mammary epithelial organoids examined. Real-time RT-PCR studies indicated that
      loss or downregulation of SFRP1 expression in tumors is frequently associated
      with promoter hypermethylation. In addition, breast cancer cell lines with SFRP1
      promoter hypermethylation reexpressed SFRP1 mRNA after treatment with 5-azaC,
      implying that DNA methylation is the predominant epigenetic mechanism for SFRP1
      gene silencing. These findings suggest that frequent downregulation of SFRP1
      expression in breast cancer can be attributed, in large part, to aberrant
      promoter hypermethylation in conjunction with or without histone deacetylation.
      Based on the frequency of tumor-specific hypermethylation in this gene, SFRP1
      could provide a valuable marker for breast cancer.

PMID- 16410722
TI  - Connecting p63 to cellular proliferation: the example of the adenosine deaminase
      target gene.
AB  - An unresolved issue regards the role of p73 and p63, the two homologs of the p53
      oncosuppressor gene, in normal cells and in tumor development. Specific target
      genes for each protein need to be identified and characterized in order to
      understand the specific role of each protein in tumor initiation and progression
      as well as in oncosuppression and development. We tested whether p63 is
      implicated in transcriptional events related to sustaining cell proliferation by
      transactivation of antiapoptotic and cell survival target genes such as Adenosine
      Deaminase (ADA), an important gene involved in cell proliferation. We demonstrate
      that ADA is a direct target gene of p63 isoforms. In human keratinocytes, the
      rate of proliferation and the high level of ADA transcript diminished upon
      elimination of p63 by small interfering RNA. Reporter assays and chromatin
      immunoprecipitation experiments indicate a physical interaction of p63 with the
      two putative p53 binding sites we identified in the ADA gene. Moreover, in
      response to p53 stabilization and DeltaNp63 downregulation in normal
      keratinocytes after U.V. treatment, we found a change in the transcriptional
      pattern of the p53 family target genes, consistent with the different roles
      played by p53 and p63 in tumor suppression and cellular proliferation. In fact
      p53 upregulation determined an increase in p21, which in turn mediated the cell
      cycle arrest, while the downregulation of DeltaNp63 determined a marked decrease
      in ADA transcript. The experiments reported here support the hypothesis that
      TAp63 and DeltaNp63 might contribute to tumor genesis not exclusively by
      antagonizing p53, but by conferring a proliferative potential on cancer cells
      through the transactivation of target genes indispensable for cell division, such
      as the Adenosine Deaminase gene.

PMID- 16410724
TI  - The SHREW1 gene, frequently deleted in oligodendrogliomas, functions to inhibit
      cell adhesion and migration.
AB  - Allelic loss of the short arm of chromosome 1 has been observed frequently in
      oligodendroglioma (60-80%). We evaluated 177 oligodendroglial tumor samples and
      defined a consensus region of deletion of approximately 630 kb. This region
      contains a single gene, SHREW1, which encodes a novel transmembrane protein in
      adherens junctions. Whereas a mutation was not detected in the coding region of
      the SHREW1 gene in oligodendrogliomas, restoration of SHREW1 expression resulted
      in suppression of cell adhesion and migration. Thus, SHREW1 inactivation may play
      a role in the development of oligodendroglial tumors.

PMID- 16410725
TI  - Redox control of manumycin A-induced apoptosis in anaplastic thyroid cancer
      cells: involvement of the xenobiotic apoptotic pathway.
AB  - Our previous studies demonstrated that manumycin A, a farnesyltransferase
      inhibitor, induced apoptosis of anaplastic thyroid cancer cells via the intrinsic
      apoptosis pathway and induced reactive oxygen species (ROS), which mediated DNA
      damage. In this study, we investigated the hypothesis that the mechanism of
      apoptosis induced by manumycin in anaplastic thyroid cancer cells fits the
      general pattern of the "xenobiotic apoptosis pathway," the hallmarks of which are
      induction of oxidative stress, mitogen-activated protein kinase (MAPK) signaling,
      and cytochrome c release, which activates the intrinsic apoptosis pathway. We
      found that manumycin reduced intracellular glutathione and generated ROS: nitric
      oxide and superoxide anions. Manumycin-induced apoptosis correlated with increase
      in ROS. Quenching of ROS with N-acetyl-L-cysteine prevented cytochrome c release
      by manumycin. Manumycin induced phosphorylation of p38 MAPK, which was blocked by
      N-acetyl-L-cysteine. p38 MAPK may be an important signaling mediator in the
      activation of the intrinsic apoptotic pathway by manumycin because the p38 MAPK
      inhibitor SB203580 inhibited cytochrome c release and activation of caspase-3 by
      manumycin. In conclusion, manumycin activated the intrinsic apoptosis pathway via
      activation of p38 MAPK by oxidative stress. The mechanism of apoptosis induced by
      manumycin fits the emerging general pattern for apoptosis induced by xenobiotics.

PMID- 16410726
TI  - Resistant starch prevents colonic DNA damage induced by high dietary cooked red
      meat or casein in rats.
AB  - In a previous study we have shown that high levels of dietary protein (as casein)
      result in increased levels of colonic DNA damage, measured by the comet assay,
      and thinning of the colonic mucus layer in rats when dietary resistant starch
      (RS) is negligible. Feeding RS abolishes these effects. This study aimed to
      establish whether a diet high in protein as cooked red meat would have similar
      effects and whether RS was protective. Rats were fed a diet containing 15% or 25%
      casein or 25% cooked lean red beef, each with or without the addition of 48% high
      amylose maize starch (a rich source of RS) for four weeks. As expected, high
      dietary casein caused a 2-fold increase in colonic DNA damage compared with a low
      casein diet and reduced the thickness of the colonic mucus layer by 41%. High
      levels of cooked meat caused 26% greater DNA damage than the high casein diet but
      reduced mucus thickness to a similar degree to casein. Addition of RS to the diet
      abolished the increase in DNA damage and the loss of colonic mucus thickness
      induced by either high protein diet. Cecal and fecal short chain fatty acid pools
      were also increased by inclusion of RS in the diet. Because DNA damage is an
      early step in the initiation of cancer, these findings suggest that increased DNA
      damage due to high dietary protein as cooked red meat or casein could increase
      colorectal cancer risk but inclusion of resistant starch in the diet could
      significantly reduce that risk.

PMID- 16410727
TI  - From cell cycle to differentiation: an expanding role for cdk6.
AB  - Over ten years ago, cdk6 was identified as a new member in a family of vertebrate
      cdc-2 related kinases. This novel kinase was found to partner with the D-type
      cyclins and to possess pRb kinase activity in vitro. Recently, several
      independent studies in multiple cell types have indicated a novel role for cdk6
      in differentiation. Since exit from the cell cycle is a necessary step in the
      process of differentiation, it may not seem surprising that downregulation of a
      mitogenic factor may be required for this process. It is, however, surprising
      that this association has not been previously uncovered and that it is apparently
      not shared with cdk4, long understood to be a functional homolog of cdk6. As this
      story unfolds it will be important to discover if the role of cdk6 in
      differentiation is pRb-dependent or pRb-independent, since pRb has long been
      established as a key factor in initiating and maintaining cell cycle exit during
      differentiation.

PMID- 16410728
TI  - The pluripotency of hair follicle stem cells.
AB  - The hair follicle bulge area is an abundant, easily accessible source of actively
      growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem
      cells, is also expressed in follicle stem cells as well as their immediate
      differentiated progeny. The nestin-expressing hair follicle stem cells
      differentiated into neurons, glial cells, keratinocytes and smooth muscle cells
      in vitro. Hair-follicle stem cells were implanted into the gap region of a
      severed sciatic nerve. The hair follicle stem cells greatly enhanced the rate of
      nerve regeneration and the restoration of nerve function. The follicle stem cells
      transdifferentiated largely into Schwann cells which are known to support neuron
      regrowth. Function of the rejoined sciatic nerve was measured by contraction of
      the gastrocnemius muscle upon electrical stimulation. After severing the tibial
      nerve and subsequent transplantation of hair-follicle stem cells, the
      transplanted mice recovered the ability to walk normally. These results suggest
      that hair-follicle stem cells provide an important accessible, autologous source
      of adult stem cells for regenerative medicine.

PMID- 16410729
TI  - Beta-cell growth: an unusual paradigm of organogenesis that is cyclin D2/Cdk4
      dependent.
AB  - Improved understanding of the signals that regulate growth and maintenance of
      adult beta-cells remains one of the main challenges in diabetes research.
      However, new advances in identifying the specific components involved in G1 cell
      cycle progression of beta-cells suggest that the molecular determinants of this
      pathway could ultimately be revealed. We find that cyclin D2, and to a minor
      degree cyclin D1, are required for adult beta-cell growth. Our observations
      complement previous data regarding cdk4, and suggest that mitogenic signals could
      act via this pathway to influence acquisition of adult beta-cell mass. Although
      cyclin D2/cdk4 activity is critically important for beta-cell growth, it was
      unclear how much ongoing replication is required to maintain beta-cell mass. Our
      recent long-term beta-cell labeling studies reveal that adult beta-cells could
      conceivably live for the life of the organism. This new paradigm of long-lived
      beta-cells challenges previous notions of rapid turnover of adult beta-cell mass.
      Thus, much remains to be learned in order to expand adult beta-cell mass in
      diabetes patients.

PMID- 16410730
TI  - Fbxo7 gets proactive with cyclin D/cdk6.
AB  - Although all three D cyclins bind and activate cdks 2, 4 and 6, Fbxo7 has been
      characterised as a selective enhancer of cdk6 activity. It increases activation
      by directly facilitating cdk6 interaction with viral and cellular D cyclins.
      Fbxo7 overexpression has transforming activity in murine fibroblasts, and it is
      also highly expressed in human cancers, suggesting it is a potential oncogene.
      Fbxo7 has the ability to activate cell cycle regulators, and is part of an E3
      ubiquitin ligase. We postulate Fbxo7 coordinates the ubiquitination of its
      substrates with cell cycle entry. It may therefore represent a means to integrate
      cell signals and control disparate biological processes during the early part of
      the cell cycle.

PMID- 16410732
TI  - Evolutionary origins of Notch signaling in early development.
AB  - Notch signaling is known to play key roles in early embryonic development and in
      the specification or patterning of germ layers in several lower organisms. Thus
      it is surprising that the removal of maternal and zygotic protein O
      fucosyltransferase 1 (Pofut1), an essential component of the canonical Notch
      signaling pathway, does not affect early embryogenesis in the mouse. Mouse
      embryos lacking Pofut1 develop normally through blastogenesis to E8.0 when all
      three germ layers have formed. Here we summarize roles for Notch signaling in
      early embryonic development of several species, and discuss the potential
      evolutionary origins of these roles. We propose that Notch signaling might have
      first been used in the common ancestor of the metazoa for certain advanced
      developmental processes such as segmentation, and only later in evolution been
      coopted for use at early stages of embryogenesis in some organisms.

PMID- 16410731
TI  - Ubiquitination of cyclin-dependent kinase inhibitor, Xic1, is mediated by the
      Xenopus F-box protein xSkp2.
AB  - In the frog, Xenopus laevis, the Cip/Kip-type cyclin-dependent kinase (CDK)
      inhibitor, Xic1, inhibits DNA replication in interphase egg extracts through the
      binding of CDK2-cyclins and Proliferating Cell Nuclear Antigen (PCNA). During DNA
      polymerase switching in the replicating Xenopus egg extract, Xic1 is targeted for
      ubiquitination and degradation when localized to chromatin through its binding to
      PCNA. To date, the machinery responsible for Xic1 ubiquitination is unknown and
      although it is predicted that the E3 called SCF may mediate Xic1 ubiquitination,
      characterization of the SCF in Xenopus is lacking. In this study, we describe the
      identification and characterization of Xenopus Skp2 (xSkp2) and the role of xSkp2
      in the ubiquitination of Xic1. Our results indicate that the expression of xSkp2
      appears to be developmentally regulated with low protein levels found in the egg
      and increased levels found in the developing embryo. We also demonstrate that
      when ectopically expressed, a xSkp2 F-box deletion mutant inhibits the initiation
      of DNA replication suggesting a role for the SCF in the onset of S phase in
      Xenopus egg extracts. We further show that xSkp2 binds to C-terminal residues of
      Xic1 and when coexpressed with Skp1, promotes the proteolysis of Xic1 in the egg
      extract. Moreover, the xSkp2 F-box deletion mutant inhibits the DNA-dependent
      ubiquitination and proteolysis of Xic1 when added to the interphase egg extract.
      Importantly, our studies demonstrate that SCF(xSkp2) supports the ubiquitination
      of Xic1 in a reconstituted in vitro ubiquitination assay and that this Xic1
      ubiquitination does not require either CDK2-cyclins or Cks1. These studies
      provide the first characterization of the SCF in Xenopus and its role in the
      ubiquitination of CDK inhibitor, Xic1, during DNA replication initiation.

PMID- 16410734
TI  - Rationale and methodology of monitoring ambulatory blood pressure and arterial
      compliance in the Hypertension in the Very Elderly Trial.
AB  - OBJECTIVE: This article describes the rationale and methodology for the
      monitoring of ambulatory blood pressure and arterial compliance in hypertensive
      patients aged 80 years and above. This is a side project of the Hypertension in
      the Very Elderly Trial. METHODS: The hypertension in the Very Elderly Trial is a
      multicentre, double-blind, randomized, placebo-controlled trial aiming to
      investigate the effect of active treatment on cardiovascular and other outcomes
      in hypertensive patients aged 80 years or more. Patients are randomized to
      placebo or active treatment starting with the diuretic indapamide and adding the
      angiotensin-converting enzyme inhibitor perindopril if required. This study has
      completed a pilot trial and the main trial is now underway. Six hundred patients
      will have two ABPM recordings, the first at baseline and the second a year after
      randomization. Arterial compliance is measured using the Q wave
      (electrocardiogram) to Korotkoff diastole sound interval. RESULTS: Baseline
      characteristics for the first 50 patients recruited are presented. CONCLUSION:
      This side project will allow the investigation of 24-h ambulatory measures of
      blood pressure and arterial compliance as predictors of cerebrovascular and
      cardiovascular events in the very elderly. The project will also allow the
      investigation of the blood pressure and vascular compliance profiles in the very
      elderly and their changes with posture. The association between these
      measurements and mortality and morbidity in this age group will be addressed.

PMID- 16410735
TI  - Ambulatory blood pressure monitoring and target organ damage: effects of age and
      sex.
AB  - OBJECTIVE: The objective of the present study was to investigate the effect of
      age and sex in the ambulatory blood pressure measurements, and target organ
      damage. METHODS: A total of 1596 patients (50.6% male and 49.4% female), aged 10
      87 years, referred to our Hypertension Center for borderline hypertension,
      underwent 24-h ambulatory blood pressure monitoring, left ventricular
      echocardiography and measurement of intima-media thickness of carotid arteries.
      RESULTS: Adolescent girls had higher mean 24-h and clinic systolic and diastolic
      blood pressure values than adolescent boys. Men aged 20-60 years had higher mean
      24-h and clinic systolic and diastolic blood pressure values than women of the
      same age. Men older than 60 years had higher mean 24-h systolic and diastolic
      blood pressure values than women of the same age, but women older than 60 years
      had higher clinic systolic and diastolic blood pressure values. White-coat effect
      increased with age in both sexes, but the magnitude of the white-coat effect was
      higher in women than in men at older ages. Men had higher left ventricular mass
      corrected for body surface area or height than women in all ages and
      significantly higher differences in ages between 30 and 80 years. In addition,
      men had greater carotid intima-media thickness than women in all ages and
      significantly higher differences in ages between 30 and 80 years. CONCLUSIONS:
      Men have greater ambulatory blood pressure values and target organ damage than
      women of the same age.

PMID- 16410737
TI  - Evaluation of cuff-wrapping methods for the determination of ankle blood
      pressure.
AB  - OBJECTIVE: The ankle-brachial index, which is calculated by dividing ankle
      systolic blood pressure by brachial systolic blood pressure, is useful in
      diagnosing peripheral arterial disease. Consensus has not been reached, however,
      on a standard method for measuring ankle systolic blood pressure. This study
      evaluated two cuff-wrapping methods for measuring ankle systolic blood pressure,
      compared with intra-arterial pressure as a gold standard. METHODS: Study
      participants were 24 consecutive adult patients who underwent surgery under
      general anesthesia at Kyoto Prefectural University Hospital in Japan between
      January and March 2002. Indirect ankle systolic blood pressure was measured in
      the posterior tibial artery using a Doppler device and two cuff-wrapping methods:
      spiral, and straight. Direct ankle systolic blood pressure was measured in the
      dorsalis pedis artery. RESULTS: Mean difference in ankle systolic blood pressure
      between indirect and direct measurements (indirect minus direct) was 1.4 mmHg
      [standard deviation of the difference (SDd), 17.6 mmHg] with the straight method
      and -1.4 mmHg (SDd, 22.2 mmHg) with the spiral method. The limit of agreements
      (mean difference +/-2 SDd) and intraclass correlation coefficient between two
      observers were -17.6 to 20.1 mmHg and 0.94, respectively, for the straight method
      and -39.4 to 40.0 mmHg and 0.78, respectively, for the spiral method.
      CONCLUSIONS: The straight method, the same cuff-wrapping method used for
      measuring brachial blood pressure, appears to represent a more suitable wrapping
      method because of better interobserver reproducibility. Accuracy and
      reproducibility of indirect ankle systolic blood pressure measurement, however,
      were not adequately improved by either of the wrapping methods.

PMID- 16410736
TI  - Reproducibility of postural changes of blood pressure in hypertensive elderly
      patients in primary care.
AB  - OBJECTIVE: To determine the reproducibility of postural changes of blood pressure
      among hypertensive elderly patients in a primary care setting. METHODS:
      Measurements of blood pressure were carried out in 60 community-dwelling
      hypertensive patients aged 65 years or more, in a sitting position and after 1
      min and 3-min standing, and were repeated not more than 10 days later. RESULTS: A
      significant (P<0.05) fall in systolic and diastolic sitting blood pressure was
      observed between the first visit (151.1+/-20.8/79.7+/-10.1 mmHg) and the second
      visit (143.5+/-20.6/76.8+/-10.9 mmHg). The intraclass correlation coefficients of
      the repeated measurements were 0.46 (CI: 0.23-0.65) and 0.42 (CI: 0.17-0.61) for
      the changes in systolic blood pressure after 1- and 3-min standing, and 0.55 (CI:
      0.34-0.71) and 0.40 (CI: 0.16-0.60) for diastolic blood pressure after 1- and 3
      min standing, respectively. The repeatability coefficients were greater for the
      orthostatic changes of blood pressure (54-65%), which indicates lower
      reproducibility, than for the blood pressure levels on both visits (31-44%).
      CONCLUSIONS: The reproducibility of the postural changes of blood pressure found
      in hypertensive elderly patients in primary care is poor. This should be taken
      into account when making diagnoses of orthostatic hypotension in this type of
      patient.

PMID- 16410738
TI  - Validation of the Omron 705IT (HEM-759-E) oscillometric blood pressure monitoring
      device according to the British Hypertension Society protocol.
AB  - BACKGROUND: The Omron 705IT (HEM-759-E, Omron Corporation, Kyoto, Japan) is an
      automated oscillometric upper arm blood pressure monitor for the professional and
      home use markets. The aim of this study was to validate the accuracy of this
      device according to the British Hypertension Society and the Association for the
      Advancement of Medical Instrumentation SP10 validation criteria. METHODS: Study
      participants were recruited until a total of 85 were obtained that filled the
      blood pressure categories specified by the British Hypertension Society protocol.
      Recruitment to the study was from the general medical and specialist clinics and
      from the staff at Guy's & St Thomas' Hospital in London, UK. Nine sequential same
      arm blood pressure readings were taken from each participant by two trained
      observers, alternating between mercury reference sphygmomanometers and the Omron
      705IT (HEM-759-E). The differences between the reference and test device
      readings, for both systolic and diastolic pressures, were compared with British
      Hypertension Society and Association for the Advancement of Medical
      Instrumentation criteria to determine the outcome of the study. RESULTS: The
      Omron 705IT (HEM-759-E) is graded 'A' for systolic and 'A' for diastolic blood
      pressures according to the British Hypertension Society criteria. The mean
      (standard deviation) of the difference between the observer and the device
      measurements was 0.60 (6.0) mmHg for systolic and -3.15 (6.6) mmHg for diastolic
      pressures, respectively. The device, therefore, also satisfies the Association
      for the Advancement of Medical Instrumentation SP10 standard, that requires
      differences of less than +/-5 (8) mmHg. CONCLUSIONS: The Omron 705IT (HEM-759-E)
      achieved an 'A/A' performance classification under the British Hypertension
      Society criteria and passes the Association for the Advancement of Medical
      Instrumentation requirements for the study population. It can be recommended for
      professional and home-use in an adult population.

PMID- 16410739
TI  - Reliability of a noninvasive device to measure systemic hemodynamics in
      hemodialysis patients.
AB  - OBJECTIVE: To evaluate the reliability of a noninvasive hemodynamic monitor in
      hemodialysis patients. METHODS: We enrolled 15 male patients (mean age 63+/-12
      years) on stable chronic hemodialysis. Blood pressure and hemodynamic readings
      were obtained with the Dynapulse 500 Guardian device (Pulsemetric Inc., San
      Diego, California, USA), which measures systemic hemodynamics on the basis of
      oscillometric waveforms obtained through a cuff placed over the brachial artery.
      Measurements were taken sequentially, in duplicate, before, during and after
      hemodialysis, in the supine, seated and standing positions on four separate
      midweek dialysis sessions over a 2-week period. RESULTS: The repeatability of the
      method was tested using 200 pairs of valid measurements. The average values (+/
      SD) were 137+/-22 mmHg for systolic blood pressure, 80+/-13 mmHg for diastolic
      blood pressure, 76+/-15 bpm for heart rate, 1320+/-268 mmHg/s for dP/dtmax, 2.8+/
      0.5 l/min/m for cardiac index, and 1455+/-359 dyn/s/cm for systemic vascular
      resistance. The mean differences (+/-SD of the difference) between readings were
      0.1+/-10.4 mmHg for systolic blood pressure, 0.3+/-6.0 mmHg for diastolic blood
      pressure, -0.2+/-8.0 bpm for heart rate, 0.2+/-234 mmHg/s for dP/dtmax, 0.03+/
      0.26 l/min/m for cardiac index and -10+/-177 for systemic vascular resistance,
      yielding limits of agreement (95%) of -20 to 20 mmHg for systolic blood pressure,
      -11 to 12 mmHg for diastolic blood pressure, -16 to 17 bpm for heart rate, -458
      to 458 mmHg/s for dP/dtmax, -0.5 to 0.5 l/min/m for cardiac index and -338 to 357
      dyn/s/cm for systemic vascular resistance. Other hemodynamic parameters fared
      similarly, and coefficients of variation were all between 7 and 18%. CONCLUSION:
      We conclude that the Dynapulse 500 Guardian has adequate reliability indices in
      hemodialysis patients.

PMID- 16410740
TI  - Performance of the automated BpTRU measurement device in the assessment of white
      coat hypertension and white-coat effect.
AB  - OBJECTIVES: BpTRU (VSM MedTech Ltd, Vancouver, Canada) is an automated
      oscillometric device that provides serial blood pressure measurements in an
      office setting in the absence of a healthcare professional. We sought to
      determine whether the white-coat effect is reduced by a blood pressure
      measurement protocol using BpTRU compared with casual office measurements.
      Secondarily, we also sought to determine whether a blood pressure measurement
      protocol using BpTRU reduced white-coat hypertension compared with the casual
      office measurements, and reduced white-coat effect and white-coat hypertension
      compared with blood pressure obtained by a research nurse. METHODS: Blood
      pressure was measured in 107 adult hypertensive patients referred for ambulatory
      blood pressure monitoring using an ambulatory blood pressure monitor, a
      standardized protocol by a trained research nurse, and a protocol using BpTRU
      (five readings over 25 min, using the 5-min blood pressure measurement interval
      setting). Casual office blood pressure was also recorded in the family
      physicians' offices. Using the mean daytime ambulatory blood pressure as the
      reference standard, the proportion of patients with white-coat effect and white
      coat hypertension were determined for measurements obtained by BpTRU, the
      research nurse, and the family physicians' offices. RESULTS: Casual office blood
      pressure measurements demonstrated a white-coat effect in 39 (36.4%) patients;
      seven (6.5%) patients demonstrated a white-coat effect using BpTRU (P<0.0001).
      White-coat hypertension was also less common using BpTRU than with the casual
      office readings (13 vs. 1 patient, P<0.0001). White-coat effect was also reduced
      with BpTRU compared with the research nurse measurements. Unfortunately,
      percentage agreement for the diagnosis of hypertension between the protocol using
      BpTRU and the reference standard was only 48%. This resulted in substantial
      misclassification of hypertension by the BpTRU measurement protocol. CONCLUSIONS:
      Although BpTRU reduces white-coat effect and white-coat hypertension, blood
      pressure is underestimated by the device, leading to misclassification of
      hypertension. BpTRU, when set at 5-min blood pressure measurement intervals,
      should not be used in clinical practice.

PMID- 16410741
TI  - The comparison of noninvasive hemodynamic monitoring with impedance cardiography
      and measurements using semicontinuous thermodilution via a pulmonary artery
      catheter in 11 patients in a study of a vasodilator drug.

PMID- 16410743
TI  - Central and extrapontine myelinolysis: then...and now.
AB  - In this review, we emphasize neuropathologic and neurobehavioral aspects of
      central pontine and extrapontine myelinolysis (CPM/EPM), also known as the
      osmotic demyelination syndrome. The literature is reviewed from the time of the
      initial report in 1959 and from key developments that have occurred more
      recently. Particular consideration is given to pathogenic mechanisms as revealed
      by recent animal studies. The role of white matter pathology in neurobehavioral
      dysfunction is also considered. The "then" and "now" of CPM and EPM tell 2
      different stories. Yet, in many respects, this expansion of information over the
      past nearly 50 years simply represents a continuum, as well as recognition, of
      the vast gaps that still persist in our understanding of this disorder.

PMID- 16410744
TI  - Genetic alterations in primary glioblastomas in Japan.
AB  - Current knowledge of genetic alterations in glioblastomas is based largely on
      genetic analyses of tumors from mainly caucasian patients in the United States
      and Europe. In the present study, screening for several key genetic alterations
      was performed on 77 primary (de novo) glioblastomas in Japanese patients. SSCP
      followed by DNA sequencing revealed TP53 mutations in 16 of 73 (22%)
      glioblastomas and PTEN mutations in 13 of 63 (21%) cases analyzed. Polymerase
      chain reaction (PCR) showed EGFR amplification in 25 of 77 (32%) cases and p16
      homozygous deletion in 32 of 77 (42%) cases. Quantitative microsatellite analysis
      revealed LOH 10q in 41 of 59 (69%) glioblastomas. The frequencies of these
      genetic alterations were similar to those reported for primary glioblastomas at
      the population level in Switzerland. As previously observed for glioblastomas in
      Europe, there was a positive association between EGFR amplification and p16
      deletion (p=0.009), whereas there was an inverse association between TP53
      mutations and p16 deletion (p=0.049) in glioblastomas in Japan. Multivariate
      analyses showed that radiotherapy was significantly predictive for longer
      survival of glioblastoma patients (p=0.002). SSCP followed by DNA sequencing of
      the kinase domain (exons 18-21) of the EGFR gene revealed mutations in 2 ou of 69
      (3%) glioblastomas in Japan and in 4 of 81 (5%) glioblastomas in Switzerland. The
      allele frequencies of polymorphisms at codon 787 CAG/CAA (Gln/Gln) in
      glioblastomas in Japan were G/G (82.4%), G/A (10.8%), A/A (6.8%), corresponding
      to G 0.878 versus A 0.122, significantly different from those in glioblastomas in
      Switzerland: G/G (27.2%), G/A (28.4%), A/A (44.4%), corresponding to G 0.414
      versus A 0.586 (p < 0.0001). These results suggest that primary glioblastomas in
      Japan show genetic alterations similar to those in Switzerland, suggesting a
      similar molecular basis in caucasians and Asians, despite different genetic
      backgrounds, including different status of a polymorphism in the EGFR gene.

PMID- 16410745
TI  - Thrombin and prothrombin are expressed by neurons and glial cells and accumulate
      in neurofibrillary tangles in Alzheimer disease brain.
AB  - Thrombin is a serine protease that is generated by proteolytic cleavage of its
      precursor, prothrombin. We previously showed that thrombin proteolyses the
      microtubule-associated protein tau and that phosphorylation of tau inhibits this
      process. To characterize further the role of thrombin in the brain, we
      investigated prothrombin and thrombin expression in cultured brain cells and in
      brains of control, Alzheimer disease (AD) and parkinsonism-dementia complex of
      Guam (PDCG). We show by reverse transcriptase-polymerase chain reaction that
      prothrombin mRNA is expressed in brain tissues, neuroblastoma cells, and cultured
      human astrocytes, oligodendrocytes, and microglial cells. We also show by
      immunohistochemistry that the proteins prothrombin and thrombin are present in
      brain using specific monoclonal and polyclonal antibodies for both proteins. All
      antibodies stained residual serum in blood vessels, as well as normal pyramidal
      neurons and their processes, and some astrocytes. Additionally, in AD and PDCG
      cases, all antibodies stained extra- and intracellular neurofibrillary tangles
      (NFTs), senile plaques, and reactive microglial cells. The ubiquitous expression
      of prothrombin and thrombin in brain cells suggests that thrombin plays an
      important physiological role in normal brain. The accumulation of thrombin and
      prothrombin in NFTs supports the hypothesis that thrombin may be involved in tau
      proteolysis and that failure to metabolize tau may lead to its aggregation in
      neurodegenerative diseases.

PMID- 16410746
TI  - Expression of vascular endothelial growth factor and its receptors in the central
      nervous system in amyotrophic lateral sclerosis.
AB  - Vascular endothelial growth factor (VEGF) prolongs survival in the mutant SOD1
      transgenic mouse model of amyotrophic lateral sclerosis (ALS), whereas
      dysregulation of VEGF through deletion of its hypoxia-regulatory element causes
      motor neuron degeneration in mice. We investigated the expression of VEGF and its
      major agonist receptors in the normal central nervous system and in patients with
      ALS. Immunohistochemistry demonstrated similar expression patterns of VEGF and
      VEGF receptor 2 (VEGFR2) in the spinal cord with finely punctate staining of the
      neuropil and strong expression in anterior horn cells (AHCs). Granular staining
      on the surface of some AHCs, similar to that seen with synaptic markers,
      suggested synaptic labeling. VEGFR2 staining was reduced in the neuropil of ALS
      cases (p=0.018) associated with a reduction of synaptophysin but not SNAP25
      expression. A greater proportion of AHCs in ALS cases showed low expression of
      VEGF (p=0.006) and VEGFR2 (p=0.009) compared with controls. Expression of VEGF
      and VEGFR2 was confirmed by Western blotting and quantitative reverse
      transcriptase-polymerase chain reaction (QPCR). The similar expression patterns
      of VEGF and VEGFR2 suggests autocrine/paracrine effects on spinal motor neurons,
      and the reduction in their expression seen in ALS cases would support the
      hypothesis that, as in mouse models of the disease, reduced VEGF signaling may
      play a role in the pathogenesis of ALS.

PMID- 16410747
TI  - Myoinositol administration improves survival and reduces myelinolysis after rapid
      correction of chronic hyponatremia in rats.
AB  - When chronic hyponatremia is rapidly corrected, reaccumulation of brain organic
      osmolytes is delayed and brain cell shrinkage occurs, leading to the osmotic
      demyelination syndrome (ODS). We hypothesized that treatment with myoinositol, a
      major organic osmolyte, could prevent ODS. Severe hyponatremia was induced in
      adult male rats by administration of arginine vasopressin and intravenous
      infusion of dextrose and water. Sixty-four hours after induction of hyponatremia,
      all animals underwent rapid correction of hyponatremia with infusion of
      hypertonic saline over 4 hours, increasing the serum sodium from 105 to 135 mM;
      half of the animals were also given myoinositol intravenously beginning 20
      minutes before correction and continuing for 28 hours. Serum sodium
      concentrations were equivalent in both groups at all time points. At 7 days, 7 of
      8 animals that received myoinositol survived compared with one of the 9 control
      animals (p < 0.01). In a second study, sodium was reduced to 106 mM over 64 hours
      in 24 animals and then corrected by 20 mM over 4 hours with concomitant loading
      and infusion of either mannitol (control) or myoinositol. Animals were killed 96
      hours after correction of hyponatremia was begun. Myoinositol-treated animals had
      significantly fewer demyelinating lesions than mannitol (2.25 +/- 1.1 versus 6.42
      +/- 1.4 lesions/brain, p < 0.03). We conclude that myoinositol administration
      improves survival and reduces myelinolysis after rapid correction of chronic
      hyponatremia in rats.

PMID- 16410748
TI  - Nuclear pore complex proteins in Alzheimer disease.
AB  - Ultrastructural studies of neurofibrillary tangles in Alzheimer disease (AD) have
      demonstrated a close relationship between nuclear pores and the cytoplasmic
      paired helical filaments comprising the tangles, as well as nuclear irregularity
      in many tangle-bearing neurons; nuclear pore aggregation has been observed in
      nearby neurons. These observations prompted examination of the nuclear pore
      complex (NPC) and proteins critical to nucleocytoplasmic transport in neurons
      with and without tangles in AD and control cases. Light microscopic study of
      hippocampus and neocortex in AD and controls revealed that all nuclei were
      labeled by antibodies to NPC proteins, including the central transporter
      nucleoporin Nup62. Nucleoporin and tau label revealed significantly more nuclear
      irregularity in AD, often associated with neurofibrillary tangles. Double label
      of Nup62 with apoptotic markers (TUNEL and active caspase-3) and a cell-cycle
      protein (cyclin B1) revealed no clear relationship of nuclear irregularity to
      apoptosis or cell-cycle protein expression. However, cytoplasmic accumulation of
      nuclear transport factor 2 (NTF2), a protein that transports cargo from the
      cytoplasm into the nucleus, was observed in a subset of hippocampal neurons with
      and without tangles in AD but not control cases. Further investigation of the NPC
      and nucleocytoplasmic transport in AD is warranted.

PMID- 16410749
TI  - Deregulation of cdk5 in Hippocampal sclerosis.
AB  - Hippocampal sclerosis (HS) is the most common cause of chronic medically
      refractory epilepsy in adults. Histologically, HS is characterized by segmental
      neuronal loss and gliosis. Although neuronal loss is important to the
      pathophysiology of HS, the molecular mechanisms underlying the neuronal loss
      remain uncertain. Recently, it has been appreciated that proteins important in
      neurodevelopment may also have a role in neurodegeneration. Cyclin-dependent
      kinase 5 (cdk5), known to be crucial in development of the normal cerebral
      cortex, has now been shown as pivotal in several cell death paradigms, including
      apoptosis and necrosis. Deregulation of cdk5 by p25 causes hyperphosphorylation
      of tau and may contribute to pathology in several neurodegenerative conditions.
      Furthermore, it has been shown that after transient forebrain ischemia, cdk5
      causes specific death of CA1 neurons in the rat hippocampus by direct
      phosphorylation of the NR2A subunit of the NMDA receptor and subsequent
      excitotoxicity. Because apoptosis, necrosis, and excitotoxicity are all thought
      to contribute to neuronal loss in HS, we hypothesized that abnormalities of the
      cdk5 pathway would accompany this disorder. Surgically resected cases of HS with
      adjacent histologically normal lateral temporal cortex were examined for cdk5 and
      its activator p35/p25. We consistently found increased immunoreactivity for
      p35/p25 in surviving neurons within areas of neuronal loss compared with areas
      where neurons were preserved. Western blots showed the ratio of p25 to p35 to be
      greater in diseased hippocampi than in the adjacent histologically normal
      temporal lobe. Histone-based kinase assays demonstrated increased activity of the
      p25-cdk5 complex in HS compared with the temporal lobe despite neuronal loss in
      the hippocampal samples. Our results suggest that p25 is pathologically increased
      in HS and that deregulation of cdk5 by p25 might contribute to neuronal death in
      this condition.

PMID- 16410750
TI  - Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease:
      astrocyte-mediated neuroprotection through increased levels of glutathione
      peroxidase.
AB  - In the present study, we investigated the expression of protease-activated
      receptors (PARs), receptors for thrombin, in substantia nigra pars compacta
      (SNpc) of Parkinson disease (PD) brains and cultures of human neurons,
      astrocytes, oligodendrocytes, and microglia as determined by immunocytochemistry
      and reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of PAR-1
      was demonstrated only in glial fibrillary acidic protein-positive astrocytes in
      SNpc, and the number of astrocytes expressing PAR-1 increased in SNpc of PD as
      compared with nonneurologic control brain. Immunoreactivity for thrombin and
      prothrombin was stronger in astrocytes and the vessel walls in SNpc of PD brains.
      PAR-1 was expressed in human astrocytes and neurons, but not in oligodendrocytes
      or microglia as determined by RT-PCR. We investigated thrombin-mediated
      activation of human astrocytes. Thrombin treatment activates human astrocytes and
      induces morphologic change and a marked increase in proliferation of astrocytes.
      Increased expression of glial cell line-derived growth factor and glutathione
      peroxidase (GPx) but no change in the expression of nerve growth factor and
      inflammatory cytokines/chemokine (IL-1beta, IL-6, IL-8, MCP-1) was found in
      thrombin/PAR-activated astrocytes. Next, we studied the neuroprotective effect
      exerted by thrombin-activated astrocytes in human cerebral neuron x human
      neuroblastoma hybrid neurons. Although thrombin showed neurotoxicity against
      human hybrid neurons in a dose-dependent manner, the conditioned media derived
      from thrombin-pretreated astrocyte cultures promoted the survival of human hybrid
      neurons. The protective effect was completely inhibited with a GPx inhibitor,
      mercaptosuccinic acid, indicating that GPx released from thrombin/PAR-activated
      astrocytes is responsible for neuroprotection of hybrid neurons against thrombin
      cytotoxicity. The present study suggests that the increased expression of PAR-1
      in astrocytes in SNpc of PD brain is the restorative move taken by the brain to
      provide neuroprotection against neuronal degeneration and cell death of
      dopaminergic neurons caused by noxious insults during the progression of PD
      pathology.

PMID- 16410751
TI  - Exogenous tissue plasminogen activator enhances peripheral nerve regeneration and
      functional recovery after injury in mice.
AB  - Tissue plasminogen activator (tPA) is an essential component of the proteolytic
      cascade that lyses blood clots. Various studies also suggest that tPA plays
      important roles in the nervous system. We show that exogenous tPA or
      tPA/plasminogen (plg) promotes axonal regeneration, remyelination, and functional
      recovery after sciatic nerve injury in the mouse. Local application of tPA or
      tPA/plg 7 days after sciatic nerve crush significantly increased the total number
      of axons and myelinated axons, which is accompanied by enhanced expression of
      neurofilament. Treatment with tPA or tPA/plg reduced the deposition of
      fibrin(ogen) after nerve injury. Moreover, tPA or tPA/plg increased the number of
      macrophages and induced MMP-9 expression at the injury site, coincident with
      reduced collagen scar formation and accelerated clearance of myelin and lipid
      debris after treatment. Consequently, tPA or tPA/plg treatment protected muscles
      from atrophy after nerve injury, indicating better functional recovery. These
      results suggest that administration of exogenous tPA or tPA/plg promotes axonal
      regeneration and remyelination through removal of fibrin deposition and
      activation of MMP-9-positive macrophages, which may be responsible for myelin
      debris clearance and preventing collagen scar formation. Therefore, tPA may be
      useful for treatment of peripheral nerve injury.

PMID- 16410752
TI  - Ezrin immunoreactivity reveals specific astrocyte activation in cerebral HIV.
AB  - The actin-binding protein ezrin is associated with cellular shape changes,
      motility, tumor invasion, and lymphocyte activation. We have earlier shown that
      ezrin immunoreactivity (IR) is faintly present in normal astrocytes but increased
      in malignant human astrogliomas. We studied the role of ezrin in astrocyte
      activation, applying immunostaining on serial paraffin sections from human
      autopsied brain tissues (51 cases). Cerebral HIV infection was chosen as a model
      displaying consistent exemplary astrocyte activation. Semiquantitative ezrin-IR
      was compared with the common glial markers GFAP, ferritin, and HLA-DR in relation
      to clinical and morphologic criteria of HIV encephalopathy. In all cases with HIV
      infection, GFAP-, HLA-DR-, and ferritin-IR were elevated in comparison to normal
      brain tissues. In contrast, high ezrin-IR in HIV infection strictly correlated
      with additional HIV encephalopathy. HIV encephalopathy with particularly high
      ezrin-IR was correlated with neuronal apoptosis (TUNEL). Combined ezrin-IR and
      GFAP-IR thus reveals 2 distinct states of astrocytic activation. Normal ezrin-IR,
      when paralleled by upregulated GFAP, reflects astroglial activation not
      associated with neuronal apoptosis. High ezrin-IR indicates specific astrocyte
      stressors related to cellular damage within the central nervous system. Ezrin-IR
      might also provide a diagnostic tool for the classification of HIV
      encephalopathy.

PMID- 16410754
TI  - Letter to the editor.

PMID- 16410755
TI  - General rules for clinical and pathological recording of breast cancer 2005.

PMID- 16410756
TI  - Adacel and Boostrix: Tdap vaccines for adolescents and adults.

PMID- 16410757
TI  - Drugs in the elderly.

PMID- 16410758
TI  - Chromium supplementation.

PMID- 16410759
TI  - Nonfatal, unintentional medication exposures among young children--United States,
      2001-2003.
AB  - Young children are vulnerable to inadvertent exposure to prescription and over
      the-counter (OTC) medications, especially when these items are not stored
      securely. In 2002, according to death certificate data, 35 children aged < or =4
      years died from unintentional medication poisonings in the United States (CDC,
      unpublished data, 2005). In 2003, according to reports to U.S. poison control
      centers, pharmaceuticals accounted for 1,336,209 (55.8%) of unintentional
      chemical or substance exposures. Of those pharmaceutical exposures, 568,939
      (42.6%) involved children aged <6 years. For this report, CDC analyzed 2001-2003
      data from hospital emergency department (ED) visits reported by the National
      Electronic Injury Surveillance System--All Injury Program (NEISS-AIP). The
      results of this analysis indicated that, during 2001-2003, an estimated 53,517
      children aged < or =4 years were treated annually in U.S. EDs for unintentional
      medication exposures. An estimated 72% of these exposures were in children aged 1
      2 years. Children aged < or =4 years can reach items on a table, in a purse, or
      in a drawer, where medications are often stored; young children also tend to put
      objects they find in their mouths. Parents and others responsible for supervising
      children should store medications securely at all times, keep them out of the
      reach of children, and be vigilant in preventing access by children to daily-use
      containers such as pill boxes.

PMID- 16410760
TI  - Overweight among students in grades K-12--Arkansas, 2003-04 and 2004-05 school
      years.
AB  - Prevalence of overweight among children nearly doubled from 1976-1980 to 1999
      2002 in the United States. During 1999-2002, approximately 65% of adults aged >
      or =20 years were overweight or obese, according to the National Health and
      Nutrition Examination Survey (NHANES). Among persons aged 6-19 years during the
      same period, 31% were overweight or at risk for overweight. In 2003, the Youth
      Risk Behavior Surveillance (YRBS) survey indicated that 27% of high school
      students were overweight or at risk for overweight. Among adolescents with a body
      mass index (BMI) at or above the 95th percentile, approximately 50% will become
      obese adults, and 70% will become obese or overweight adults. Although NHANES and
      YRBS provide population-based, cross-sectional state and national samples, no
      studies reflect a national or statewide longitudinal cohort assessment of
      childhood and adolescent obesity. The American Academy of Pediatrics (AAP) and
      the Institute of Medicine recommend annual assessments of BMI as a strategy for
      preventing and combating childhood obesity. In 2003, Arkansas implemented a
      multifaceted statewide initiative to reduce and prevent overweight among
      children. A key aspect of this initiative (Act 1220) is the mandated annual
      statewide BMI assessments of all Arkansas public school students with
      confidential reporting of results to parents. This report describes the results
      of this large-scale population screening, which indicated that, during the 2003-
      04 and 2004--05 school years, 38% of Arkansas students were overweight or at risk
      for overweight. This finding suggests a more severe problem than that reported
      for other states. Because rates of childhood and adolescent obesity in certain
      areas might be higher than anticipated, health policy decisions that address
      health outcomes and cost of care should be based on state-specific, population
      based data.

PMID- 16410761
TI  - Multiple outbreaks of gastrointestinal illness among school children associated
      with consumption of flour tortillas--Massachusetts, 2003-2004.
AB  - Ten outbreaks of gastrointestinal illness among school children at nine different
      schools were reported during February 2003-May 2004 to the Massachusetts
      Department of Public Health (MDPH). These outbreaks occurred among children who
      ate lunch provided by the schools and were characterized by short incubation
      periods and short durations of illness. The clinical and epidemiologic
      characteristics of the outbreaks were similar to those of previously reported
      outbreaks of vomiting associated with burritos served at multiple schools in the
      United States in 1997-1998. Epidemiologic investigation of the 1997-1998
      outbreaks implicated burritos made with flour tortillas as the suspect vehicle;
      no etiologic agent was identified, but symptoms suggested either a biotoxin or
      chemical agent. This report describes epidemiologic and laboratory findings from
      three of the 10 outbreaks in Massachusetts. Consumption of flour tortillas from a
      single manufacturer was significantly associated with illness. Preliminary
      results indicated elevated levels, relative to common industry practices, of
      potassium bromate and calcium propionate in the implicated tortillas. School
      officials should be aware of the need for rapid action during outbreaks with
      short incubation periods and short durations and should notify local and state
      health officials immediately to ensure rapid response and collection of
      epidemiologic information, clinical specimens, and food samples.

PMID- 16410762
TI  - Genomics reveals traces of fungal phenylpropanoid-flavonoid metabolic pathway in
      the f ilamentous fungus Aspergillus oryzae.
AB  - Fungal secondary metabolites constitute a wide variety of compounds which either
      play a vital role in agricultural, pharmaceutical and industrial contexts, or
      have devastating effects on agriculture, animal and human affairs by virtue of
      their toxigenicity. Owing to their beneficial and deleterious characteristics,
      these complex compounds and the genes responsible for their synthesis have been
      the subjects of extensive investigation by microbiologists and pharmacologists. A
      majority of the fungal secondary metabolic genes are classified as type I
      polyketide synthases (PKS) which are often clustered with other secondary
      metabolism related genes. In this review we discuss on the significance of our
      recent discovery of chalcone synthase (CHS) genes belonging to the type III PKS
      superfamily in an industrially important fungus, Aspergillus oryzae. CHS genes
      are known to play a vital role in the biosynthesis of flavonoids in plants. A
      comparative genome analyses revealed the unique character of A. oryzae with four
      CHS-like genes (csyA, csyB, csyC and csyD) amongst other Aspergilli (Aspergillus
      nidulans and Aspergillus fumigatus) which contained none of the CHS-like genes.
      Some other fungi such as Neurospora crassa, Fusarium graminearum, Magnaporthe
      grisea, Podospora anserina and Phanerochaete chrysosporium also contained
      putative type III PKSs, with a phylogenic distinction from bacteria and plants.
      The enzymatically active nature of these newly discovered homologues is expected
      owing to the conservation in the catalytic residues across the different species
      of plants and fungi, and also by the fact that a majority of these genes (csyA,
      csyB and csyD) were expressed in A. oryzae. While this finding brings filamentous
      fungi closer to plants and bacteria which until recently were the only ones
      considered to possess the type III PKSs, the presence of putative genes encoding
      other principal enzymes involved in the phenylpropanoid and flavonoid
      biosynthesis (viz., phenylalanine ammonia-lyase, cinnamic acid hydroxylase and p
      coumarate CoA ligase) in the A. oryzae genome undoubtedly prove the extent of its
      metabolic diversity. Since many of these genes have not been identified earlier,
      knowledge on their corresponding products or activities remain undeciphered. In
      future, it is anticipated that these enzymes may be reasonable targets for
      metabolic engineering in fungi to produce agriculturally and nutritionally
      important metabolites.

PMID- 16410763
TI  - Degradation of crystalline cellulose by the brown-rot basidiomycete Fomitopsis
      palustris.
AB  - This study demonstrated that the brown rot basidiomycete Fomitopsis palustris was
      able to degrade crystalline cellulose (Avicel). This fungus could also produce
      the three major cellulases (exoglucanases, endoglucanases, and beta-glucosidase)
      when the cells were grown on 2.0% Avicel. Avicel degraded by F. palustris showed
      a decrease in relative crystallinity from 83% to 78.5% after 14 days of
      incubation. The characterization study indicated that optimum pH was 4.5 and
      optimum temperature was 70 degrees C for exoglucanase (cellobiohydrolase)
      activity. Hydrolysis of Avicel by the crude enzyme from F. palustris yielded 1.6
      mg/ml of glucose after 43 h, which corresponded to a cellulose conversion degree
      of 3.2%. Therefore, this study revealed for the first time that the brown rot
      basidiomycete F. palustris produces cellulases capable of yielding soluble sugars
      from crystalline cellulose.

PMID- 16410764
TI  - Safety assessment of potential lactic acid bacteria Bifidobacterium longum
      SPM1205 isolated from healthy Koreans.
AB  - The safety assessment of Bifidobacterium longum SPM1205 isolated from healthy
      Koreans and this strain's inhibitory effects on fecal harmful enzymes of
      intestinal microflora were investigated. The overall safety of this strain was
      investigated during a feeding trial. Groups of SD rats were orally administered a
      test strain or commercial reference strain B. longum 1 x 10(9) CFU/kg body
      weight/day for four weeks. Throughout this time, their feed intake, water intake
      and live body weight were monitored. Fecal samples were periodically collected to
      test harmful enzyme activities of intestinal microflora. At the end of the four
      week observation period, samples of blood, liver, spleen, kidney, and gut tissues
      were collected to determine for hematological parameters and histological
      differences. The results obtained in this experiment demonstrated that four weeks
      of consumption of this Bifidobacterium strain had no adverse effects on rat's
      general health status, blood biochemical parameters or histology. Therefore, it
      is likely to be safe for human use. Fecal harmful enzymes such as beta
      glucosidase, beta-glucuronidase, tryptophanase and urease, were effectively
      inhibited during the administration of the B. longum SPM1205. These results
      suggested that this B. longum SPM 1205 could be used for humans as a probiotic
      strain.

PMID- 16410765
TI  - Characterization of Methylophaga sp. strain SK1 cytochrome cL expressed in
      Escherichia coli.
AB  - Methylophaga sp. strain SK1 is a new restricted facultative methanol-oxidizing
      bacterium that was isolated from seawater. The aim of this study was to
      characterize the electron carriers involved in the methanol oxidation process in
      Methylophaga sp. strain SK1. The gene encoding cytochrome c(L) (mxaG) was cloned
      and the recombinant gene was expressed in Escherichia coli DH5 under strict
      anaerobic conditions. The recombinant cytochrome c(L) had the same molecular
      weight and absorption spectra as the wild-type cytochrome c(L) both in the
      reduced and oxidized forms. The electron flow rate from methanol dehydrogenase
      (MDH) to the recombinant cytochrome c(L) was similar to that from MDH to the wild
      type cytochrome c(L). These results suggest that recombinant cytochrome c(L) acts
      as a physiological primary electron acceptor for MDH.

PMID- 16410766
TI  - Purification and characterization of manganese peroxidase of the white-rot fungus
      Irpex lacteus.
AB  - The production of manganese peroxidase (MnP) by Irpex lacteus, purified to
      electrophoretic homogeneity by acetone precipitation, HiPrep Q and HiPrep
      Sephacryl S-200 chromatography, was shown to correlate with the decolorization of
      textile industry wastewater. The MnP was purified 11.0-fold, with an overall
      yield of 24.3%. The molecular mass of the native enzyme, as determined by gel
      filtration chromatography, was about 53 kDa. The enzyme was shown to have a
      molecular mass of 53.2 and 38.3 kDa on SDS-PAGE and MALDI-TOF mass spectrometry,
      respectively, and an isoelectric point of about 3.7. The enzyme was optimally
      active at pH 6.0 and between 30 and 40 degrees C. The enzyme efficiently
      catalyzed the decolorization of various artificial dyes and oxidized Mn (II) to
      Mn (III) in the presence of H(2)O(2). The absorption spectrum of the enzyme
      exhibited maxima at 407, 500, and 640 nm. The amino acid sequence of the three
      tryptic peptides was analyzed by ESI Q-TOF MS/MS spectrometry, and showed low
      similarity to those of the extracellular peroxidases of other white-rot
      basidiomycetes.

PMID- 16410767
TI  - Gibberellins-producing rhizobacteria increase endogenous gibberellins content and
      promote growth of red peppers.
AB  - The growth of red pepper plants was enhanced by treatment with the
      rhizobacterium, Bacillus cereus MJ-1. Red pepper shoots showed a 1.38-fold
      increase in fresh weight (fw) and roots showed a 1.28-fold fw gain. This plant
      growth-promoting rhizobacterium (PGPR) has been reported to produce gibberellins
      (GAs). Other GAs-producing rhizobacteria, Bacillus macroides CJ-29 and Bacillus
      pumilus CJ-69, also enhanced the fw of the plants. They were less effective than
      B. cereus MJ-1, though. The endogenous GAs content of pepper shoots inoculated
      with MJ-1 was also higher than in shoots inoculated with CJ-29 or CJ-69. When
      inoculated with MJ-1, bacterial colonization rate of the roots was higher than
      that of roots inoculated with CJ-29 or CJ-69. These results support the idea that
      the plant growth-promoting effect of the bacteria also positively related with
      the efficiency of root colonization by the bacteria. In addition, we identified
      the major endogenous GAs of the red pepper as originating from both the early C
      13 hydroxylation and the early non C-13 hydroxylation pathways, with the latter
      being the predominant pathway of GA biosynthesis in red pepper shoots.

PMID- 16410768
TI  - Role of RNA polymerase II carboxy terminal domain phosphorylation in DNA damage
      response.
AB  - The phosphorylation of C-terminal domain (CTD) of Rpb1p, the largest subunit of
      RNA polymerase II plays an important role in transcription and the coupling of
      various cellular events to transcription. In this study, its role in DNA damage
      response is closely examined in Saccharomyces cerevisiae, focusing specifically
      on several transcription factors that mediate or respond to the phosphorylation
      of the CTD. CTDK-1, the pol II CTD kinase, FCP1, the CTD phosphatase, ESS1, the
      CTD phosphorylation dependent cis-trans isomerase, and RSP5, the phosphorylation
      dependent pol II ubiquitinating enzyme, were chosen for the study. We determined
      that the CTD phosphorylation of CTD, which occurred predominantly at serine 2
      within a heptapeptide repeat, was enhanced in response to a variety of sources of
      DNA damage. This modification was shown to be mediated by CTDK-1. Although
      mutations in ESS1 or FCP1 caused cells to become quite sensitive to DNA damage,
      the characteristic pattern of CTD phosphorylation remained unaltered, thereby
      implying that ESS1 and FCP1 play roles downstream of CTD phosphorylation in
      response to DNA damage. Our data suggest that the location or extent of CTD
      phosphorylation might be altered in response to DNA damage, and that the modified
      CTD, ESS1, and FCP1 all contribute to cellular survival in such conditions.

PMID- 16410769
TI  - Screening of growth- or development-related genes by using genomic library with
      inducible promoter in Aspergillus nidulans.
AB  - Using the genomic library constructed at the downstream of the niiA promoter,
      which induces the over-expression of an inserted DNA fragment, we have attempted
      to screen the genes affecting growth or development by over-expression. The wild
      type strain was transformed using the AMA-niiA(p) library and cultured on 1.2 M
      sorbitol media, in which asexual sporulation is induced, but sexual development
      is repressed. Over 100,000 strains transformed to pyrG(+) were analyzed with
      regard to any changes in phenotype. Consequently, seven strains were isolated for
      further analyses. These strains were designated NOT [niiA(p) over-expression
      transformants] stains. Four of the strains were of the inducible type, and the
      remaining strains were of the multi-copy suppression type. Two of the inducible
      type strains, NOT1 and NOT40, harbored genes which had been inserted in reverse
      direction, suggesting that the mutant phenotypes had been derived from an excess
      amount of anti-sense mRNA. Domain analyses of the deduced polypeptides from the
      DNA fragments rescued from the transformants revealed that NOT1, NOT40 and NOT6
      harbored a LisH motif, a forkhead domain, and a Zn(II)(2)Cys(6) binuclear zinc
      cluster, respectively.

PMID- 16410770
TI  - Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein
      response.
AB  - Viral infection causes stress to the endoplasmic reticulum (ER). The response to
      endoplasmic reticulum stress, known as the unfolded protein response (UPR), is
      designed to eliminate misfolded proteins and allow the cell to recover. The role
      of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV
      replicons that induce UPR, is incompletely understood. We demonstrate that HCV
      NS4B could induce activating transcription factor (ATF6) and inositol-requiring
      enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B
      activated the IRE1 pathway, as indicated by splicing of X box-binding protein
      (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM
      (ER degradation-enhancing alpha-mannosidase-like protein, a protein degradation
      factor), was inhibited. These results imply that NS4B might induce UPR through
      ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or
      HCV subreplicon replication.

PMID- 16410771
TI  - Analysis of immune responses against nucleocapsid protein of the Hantaan virus
      elicited by virus infection or DNA vaccination.
AB  - Even though neutralizing antibodies against the Hantaan virus (HTNV) has been
      proven to be critical against viral infections, the cellular immune responses to
      HTNV are also assumed to be important for viral clearance. In this report, we
      have examined the cellular and humoral immune responses against the HTNV
      nucleocapsid protein (NP) elicited by virus infection or DNA vaccination. To
      examine the cellular immune response against HTNV NP, we used H-2K(b) restricted
      T-cell epitopes of NP. The NP-specific CD8(+) T cell response was analyzed using
      a (51)Cr-release assay, intracellular cytokine staining assay, enzyme-linked
      immunospot assay and tetramer binding assay in C57BL/6 mice infected with HTNV.
      Using these methods, we found that HTNV infection elicited a strong NP-specific
      CD8(+) T cell response at eight days after infection. We also found that several
      different methods to check the NP-specific CD8(+) T cell response showed a very
      high correlation among analysis. In the case of DNA vaccination by plasmid
      encoding nucleocapsid gene, the NP-specific antibody response was elicited 2
      approximately 4 weeks after immunization and maximized at 6 approximately 8
      weeks. NP-specific CD8(+) T cell response reached its peak 3 weeks after
      immunization. In a challenge test with the recombinant vaccinia virus expressing
      NP (rVV-HTNV-N), the rVV-HTNV-N titers in DNA vaccinated mice were decreased
      about 100-fold compared to the negative control mice.

PMID- 16410772
TI  - Molecular epidemiological analysis of bloodstream isolates of Candida albicans
      from a university hospital over a five-year period.
AB  - We assessed the genetic relations and epidemiological links among bloodstream
      isolates of Candida albicans, which were obtained from a university hospital over
      a period of five years. The 54 bloodstream isolates from the 38 patients yielded
      14 different karyotypes, 29 different patterns after digestion with SfiI (REAG
      S), and 31 different patterns after digestion with BssHII (REAG-B) when analyzed
      using three different pulsed-field gel electrophoresis (PFGE) typing methods. In
      11 patients with serial bloodstream isolates, all strains from each patient had
      the same PFGE pattern. The dendrograms for all of the strains revealed that the
      distribution of similarity values ranged from 0.70 to 1.0 in the REAG-S patterns,
      and from 0.35 to 1.0 in the REAG-B patterns. Overall, the combination of the
      three different PFGE methods identified 31 distinct types, reflecting the results
      obtained using the REAG-B alone different. different Five PFGE types were shared
      among 22 isolates from 12 patients. These types of strains were more frequently
      associated with central venous catheter-related fungemia than the other 26 type
      strains (92% versus 31%; P < 0.005). Of five PFGE types, four isolates were
      determined to be epidemiologically related: each of these types was primarily
      from two or three patients who had been hospitalized concurrently within the same
      intensive care unit. Our results suggest that the REAG-B constitutes perhaps the
      most useful PFGE method for investigating C. albicans candidemia and also shows
      that a relatively high proportion of C. albicans candidemia may be associated
      with exogenous acquisition of clonal strains.

PMID- 16410773
TI  - Purification and characterization of laccase from the white rot fungus Trametes
      versicolor.
AB  - Laccase is one of the ligninolytic enzymes of white rot fungus Trametes
      versicolor 951022, a strain first isolated in Korea. This laccase was purified
      209-fold from culture fluid with a yield of 6.2% using ethanol precipitation,
      DEAE-Sepharose, Phenyl-Sepharose, and Sephadex G-100 chromatography. T.
      versicolor 951022 excretes a single monomeric laccase showing a high specific
      activity of 91,443 U/mg for 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic
      acid) (ABTS) as a substrate. The enzyme has a molecular mass of approximately 97
      kDa as determined by SDS-PAGE, which is larger than those of other laccases
      reported. It exhibits high enzyme activity over broad pH and temperature ranges
      with optimum activity at pH 3.0 and a temperature of 50 degrees C. The Km value
      of the enzyme for substrate ABTS is 12.8 micrometer and its corresponding Vmax
      value is 8125.4 U/mg. The specific activity and substrate affinity of this
      laccase are higher than those of other white rot fungi, therefore, it may be
      potentially useful for industrial purposes.

PMID- 16410774
TI  - Production of saccharogenic and dextrinogenic amylases by Rhizomucor pusillus A
      13.36.
AB  - A newly-isolated thermophilic strain of the zygomycete fungus Rhizomucor pusillus
      13.36 produced highly active dextrinogenic and saccharogenic enzymes. Cassava
      pulp was a good alternative substrate for amylase production. Dextrinogenic and
      saccharogenic amylases exhibited optimum activities at a pH of 4.0-4.5 and 5.0
      respectively and at a temperature of 75 degrees C. The enzymes were highly
      thermostable, with no detectable loss of saccharogenic or dextrinogenic activity
      after 1 h and 6 h at 60 degrees C, respectively. The saccharogenic activity was
      inhibited by Ca(2+) while the dextrinogenic was indifferent to this ion. Both
      activities were inhibited by Fe(2+) and Cu(2+) Hydrolysis of soluble starch by
      the crude enzyme yielded 66% glucose, 19.5% maltose, 7.7% maltotriose and 6.6%
      oligosaccharides.

PMID- 16410775
TI  - Cloning of a manganese peroxidase cDNA gene repressed by manganese in Trametes
      versicolor.
AB  - White-rot fungi have the following enzyme systems for lignin degradation:
      laccase, lignin peroxidase and manganese peroxidase. There are other types of
      peroxidases related to lignin degradation, one of which we have cloned a cDNA
      gene of manganese-repressed peroxidase (MrP) in Trametes versicolor isolated in
      South Korea. The mrp transcript level has been decreased by 1 micrometer of
      Mn(2+).

PMID- 16410778
TI  - Cigarette smoking, metabolic gene polymorphism, and psoriasis.

PMID- 16410776
TI  - Molecular detection of catabolic genes for polycyclic aromatic hydrocarbons in
      the reed rhizosphere of Sunchon Bay.
AB  - This study focused on detecting catabolic genes for polycyclic aromatic
      hydrocarbons (PAHs) distributed in the reed rhizosphere of Sunchon Bay, Korea.
      These marsh and mud environments were severely affected by human activities,
      including agriculture and fisheries. Our previous study on microbial roles in
      natural decontamination displayed the possibility that PAH-degrading bacteria,
      such as Achromobacter sp., Alcaligenes sp., Burkholderia sp. and Pseudomonas sp.
      play an important decontamination role in a reed rhizosphere. In order to gain
      further fundamental knowledge on the natural decontamination process, catabolic
      genes for PAH metabolism were investigated through PCR amplification of
      dioxygenase genes using soil genomic DNA and sequencing. Comparative analysis of
      predicted amino acid sequences from 50 randomly selected dioxygenase clones
      capable of hydroxylating inactivated aromatic nuclei indicated that these were
      divided into three groups, two of which might be originated from PAH-degrading
      bacteria. Amino acid sequences of each dioxygenase clone were a part of the genes
      encoding enzymes for initial catabolism of naphthalene, phenanthrene, or pyrene
      that might be originated from bacteria in the reed rhizosphere of Sunchon Bay.

PMID- 16410779
TI  - Epidemiology of tick bites and borreliosis in children attending kindergarten or
      so-called "forest kindergarten" in southwest Germany.
AB  - The so-called "forest kindergartens" have been increasingly popular in Germany
      since the beginning of the 1990s. These are nurseries located in forested areas
      where children spend all-season full-time outdoors. Fifty-three kindergartens in
      the state of Baden-Wurttemberg, Germany participated in this study. In a
      prospective clinical cohort study, the child's personal data, history, protective
      parental habits concerning tick bites, number of tick bites, and cases of
      borreliosis were recorded monthly (March-October 2004) using a questionnaire.
      Altogether, 1,707 children of 25 "forest kindergartens" (506 children) and 28
      conventional kindergartens (1,201 children) were included. The response rate was
      75% in "forest kindergartens" and 65% in conventional kindergartens. In the
      "forest kindergartens", 1,503 tick bites especially on the trunk and on the head
      were found, whereas 502 tick bites were registered in conventional kindergartens.
      Sixteen cases of borreliosis were diagnosed (10 in "forest kindergartens", six in
      conventional kindergarten), most frequently manifesting as erythema migrans.
      Children attending a "forest kindergarten" have a 2.8 times increased risk of
      experiencing tick bites and a 4.6 times increased risk of suffering from
      borreliosis compared to conventional kindergarten in Germany, although protective
      parental behavior in "forest kindergarten" children was significantly better than
      that in conventional kindergarten.

PMID- 16410781
TI  - Wound healing is defective in mice lacking tetraspanin CD151.
AB  - The tetraspanin CD151 forms complexes in epithelial cell membranes with laminin
      binding integrins alpha6beta4, alpha3beta1, and alpha6beta1, and modifies
      integrin-mediated cell migration in vitro. We demonstrate in this study that
      CD151 expression is upregulated in a distinct temporal and spatial pattern during
      wound healing, particularly in the migrating epidermal tongue at the wound edge,
      suggesting a role for CD151 in keratinocyte migration. We show that healing is
      significantly impaired in CD151-null mice, with wounds gaping wider at 7 days
      post-injury. The rate of re-epithelialization of the CD151-null wounds is
      adversely affected, with significantly less wound area being covered by migrating
      epidermal cells. Our studies reveal that although laminin levels are similar in
      wild-type and CD151-null wounds, the organization of the laminin in the basement
      membrane is impaired. Furthermore, upregulation of alpha6 and beta4 integrin
      expression is adversely affected in CD151-null mice wounds. In contrast, we find
      no significant effect of CD151 gene knockout on alpha3 and beta1 integrin
      expression in wound repair. We suggest that mice lacking the CD151 gene are
      defective in wound healing, primarily owing to impairment of the re
      epithelialization process. This may be due to defective basement membrane
      formation and epithelial cell adhesion and migration.

PMID- 16410782
TI  - Circulating tyrosinase and MART-1 mRNA does not independently predict relapse or
      survival in patients with AJCC stage I-II melanoma.
AB  - The detection of melanoma cells in peripheral blood has been proposed to select
      patients with a high risk of relapse. In this study, tyrosinase and melanoma
      antigen recognized by T cells 1 (MART-1) mRNA expression was evaluated in serial
      samples obtained before definitive surgery and during follow-up in patients with
      American Joint Committee on Cancer stage I-II melanoma. Serial samples (n=2,262)
      were collected from 236 patients from 1997 to 2002. Analyses of the RNA samples
      were performed with a calibrated reverse transcriptase-PCR assay. Gender, age,
      primary tumor site, ulceration, thickness, Clark level, and histological subtype
      were analyzed together with tyrosinase and MART-1 mRNA treated as updated
      covariates in a Cox proportional-hazard model. After a median follow-up time of
      66 months, 42 out of 236 patients (18%) had relapsed. The following variables
      were significantly associated with relapse-free survival in the univariate
      analyses: tyrosinase, MART-1, gender, ulceration, thickness, Clark level, and
      histological subtype. Entering these covariates into a multivariate Cox analysis
      resulted in thickness as the single independent prognostic factor (P<0.0001),
      whereas MART-1 (P=0.07) approached significance at the 5% significance level. The
      serial measurements of tyrosinase and MART-1 mRNA in peripheral blood of stage I
      II melanoma patients cannot be demonstrated to have independent prognostic impact
      on relapse-free survival.

PMID- 16410783
TI  - Oncostatin M expression is functionally connected to neutrophils in the early
      inflammatory phase of skin repair: implications for normal and diabetes-impaired
      wounds.
AB  - In this study, we investigated the role of the cytokine oncostatin M (OSM) for
      wound biology. OSM and its specific OSM receptor subunit beta (OSMRbeta) were
      induced upon injury. OSM induction paralleled the early influx of
      polymorphonuclear neutrophils (PMN) into the wound. OSM protein was localized in
      PMN in very early wounds, whereas OSMRbeta could be detected on macrophages,
      keratinocytes, and fibroblasts later in repair. To establish a functional
      connection between PMN and OSM expression in wounds, we depleted mice from
      circulating PMN by injecting an anti-PMN monoclonal antibody (Ly-6G). PMN
      depleted wounds were characterized by a nearly complete loss of OSM but not
      OSMRbeta mRNA and protein expression within the initial 16-24 hours after injury.
      PMN-rich chronic wounds from diabetic ob/ob mice were characterized by a strongly
      elevated OSM mRNA and protein expression as compared to healthy animals.
      Moreover, a leptin-mediated improvement of chronic wounds in ob/ob mice was
      paralleled by a complete inhibition of PMN influx associated again with a
      dramatic loss of OSM expression at the wound site. These data constitute strong
      evidence that OSM expression during wound inflammation is functionally connected
      to PMN infiltration.

PMID- 16410784
TI  - ATPgammaS enhances the production of inflammatory mediators by a human dermal
      endothelial cell line via purinergic receptor signaling.
AB  - Adenosine 5'-triphosphate (ATP) affects multiple intra- and extracellular
      processes, including vascular tone and immune responses. Microvascular
      endothelial cells (EC) play a central role in inflammation by recruitment of
      inflammatory cells from blood to tissues. We hypothesized that ATP (secreted by
      neurons and/or released after perturbation of cutaneous cells) may influence
      secretion of inflammatory messengers by dermal microvascular EC through actions
      on purinergic P2 receptors. Addition of the hydrolysis-resistant ATP analogue,
      adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), to subconfluent cultures of the
      human microvascular endothelial cell-1 (HMEC-1) cell line led to a dose- and time
      dependent increase in release of IL-6, IL-8, monocyte chemoattractant protein-1,
      and growth-regulated oncogene alpha. Both ATPgammaS-induced release and basal
      production of these proteins were significantly inhibited by the purinergic
      antagonists pyridoxal-5'-phosphate-6-azophenyl-2',5'-disulfonic acid (PPADS),
      pyridoxal-5'-phosphate-6(2'-naphthylazo-6-nitro-4',8'-disulfonate), and suramin.
      ATPgammaS increased expression of intercellular adhesion molecule-1 (ICAM-1),
      whereas suramin and PPADS decreased both ATPgammaS-induced and basal ICAM-1
      expression. Using PCR, we found that HMEC-1 strongly express mRNA for the P2X(4),
      P2X(5), P2X(7), P2Y(2), and P2Y(11) receptors and weakly express mRNA for P2X(1)
      and P2X(3) receptors. Purinergic nucleotides may mediate acute inflammation in
      the skin and thus contribute to physiological and pathophysiological
      inflammation. For example, ATP may contribute to both the vasodilation and the
      inflammation associated with rosacea.

PMID- 16410785
TI  - Monoclonal origin of anatomically distinct basal cell carcinomas.
AB  - Basal cell carcinoma (BCC) is the most common skin tumor in Caucasians. Loss of
      heterozygosity (LOH) of chromosome 9 (9q22.3) is common in BCCs, and indirectly
      implies their monoclonal origin. Although BCCs are considered monoclonal tumors,
      the clonal origin of anatomically distinct tumors in the same patient was rarely
      investigated. Forty-one anatomically distinct BCCs from 15 female patients were
      genotyped for LOH at chromosome 9q22.3, and the inactivation pattern of X
      chromosome using the androgen receptor polymorphic site. Overall, 11 women with
      30 tumors were heterozygous (informative) with either one of the two 9q markers
      or the androgen receptor polymorphism. LOH of 9q was detected in 20 tumors from
      seven patients, and in all tumors derived from the same patient, the same allele
      was lost. An identical X-chromosome inactivation pattern was noted in all four
      tumors taken from one patient, and in another informative patient, one tumor
      demonstrated LOH and the other retained it. In five tumors from two patients,
      there was no evidence of monoclonality using either technique. We conclude that
      the majority of anatomically distinct BCCs are monoclonal neoplasms and may
      represent expansion of the same clone.

PMID- 16410786
TI  - Distinctive role of the cKit receptor tyrosine kinase signaling in mammalian
      melanocytes.
AB  - The cKit receptor plays a critical role in melanocyte physiology, influencing
      melanogenesis, proliferation, migration, and survival of the pigment-producing
      cells. However, pathways of cKit-mediated intracellular signaling and molecular
      mechanisms, which regulate specific cellular responses to the activation of the
      receptor in melanocytes, remain incompletely understood. Here, by using the
      genetically altered mouse melanocytes expressing an endogenous, constitutively
      active mutant (D814Y) cKit receptor, we investigated physiological cellular
      responses to the ligand-independent activation of the receptor tyrosine kinase.
      It was anticipated that such activation would either trigger uncontrolled
      proliferation of the melanocytes or stimulate melanin biosynthesis. In contrast
      to the expectation, we found that constitutive signaling from the cKit receptor
      did not stimulate melanogenesis and proliferation, but significantly promoted
      migration of the melanocytes both in vitro and in vivo. We also showed that such
      signaling is not associated with tumorigenic transformation of the pigment
      producing cells. Taken together, our observations suggest that, in mammalian
      melanocytes, activation of the cKit receptor tyrosine kinase is primarily
      responsible for transmission of pro-migration signals, which may antagonize
      proliferation and melanogenesis. Our data also provide an additional explanation
      as to why malignant melanocytes lose cKit expression during melanoma progression.

PMID- 16410787
TI  - CD25 expression is correlated with histological grade and response to denileukin
      diftitox in cutaneous T-cell lymphoma.
AB  - Denileukin diftitox (Ontak), a recombinant fusion protein of diphtheria toxin and
      ligand, IL-2, binds to the IL-2 receptor, is internalized, and causes cell death.
      Denileukin diftitox was approved for the treatment of cutaneous T-cell lymphomas
      (CTCLs) with CD25+ expression. We prospectively stained lesional skin biopsy
      specimens from 113 mycosis fungoides and Sezary Syndrome patients for activation
      markers CD25 and CD30 to correlate expression with clinical tumor-node metastasis
      (TNM) stage, histologic grade, and response to denileukin diftitox. High
      expression was defined as positivity of > or =20% of lesional T-cells using
      immunohistochemistry (IHC). CD25 and CD30 expression was more common in lesions
      from advanced patients (P = 0.04 and 0.002, respectively). Advanced TNM (T3 or
      T4) was significantly associated with intermediate-grade (P = 0.002) and large
      cell transformation histology (P = 0.04). Of interest, clinical responses were
      observed in 78.5% of patients with high CD25 expression versus 20% with low to
      undetectable CD25 expression (P = 0.01) among 24 patients receiving standard 5
      day infusions of denileukin diftitox at 18 microg/kg/day. These data suggest that
      high CD25 expression by IHC is associated with advanced CTCL and with clinical
      response to denileukin diftitox therapy.

PMID- 16410788
TI  - A role for regulatory T cells in cutaneous T-Cell lymphoma; induction of a CD4 +
      CD25 + Foxp3+ T-cell phenotype associated with HTLV-1 infection.

PMID- 16410789
TI  - Pseudoxanthoma elasticum is a recessive disease characterized by compound
      heterozygosity.
AB  - Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene.
      Historically, PXE has been suggested to be inherited either in an autosomal
      dominant or autosomal recessive manner. To determine the exact mode of
      inheritance of PXE and to address the question of phenotypic expression in
      mutation carriers, we identified seven pedigrees with affected individuals in two
      different generations and sequenced the entire coding region of ABCC6 in affected
      individuals, presumed carriers with a limited phenotype and unaffected family
      members. Two allelic mutations were identified in each individual with
      unambiguous diagnosis of PXE, as well as in those with only minimal clinical
      signs suggestive of PXE but with positive skin biopsy. Missense mutations were
      frequently detected in the latter cases. In conclusion, PXE is inherited in an
      autosomal recessive manner and presence of disease in two generations is due to
      pseudodominance.

PMID- 16410790
TI  - DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and
      maturation defects in the epidermis.
AB  - Desmosterolosis is an autosomal recessive disorder due to mutations in the 3beta
      hydroxysterol-Delta24 reductase (DHCR24) gene that encodes an enzyme catalyzing
      the conversion of desmosterol to cholesterol. To date, only two patients have
      been reported with severe developmental defects including craniofacial
      abnormalities and limb malformations. We employed mice with targeted disruption
      of DHCR24 to understand the pathophysiology of desmosterolosis. All DHCR24-/-
      mice died within a few hours after birth. Their skin was wrinkleless and less
      pliant, leading to restricted movement and inability to suck (empty stomach).
      DHCR24 gene was expressed abundantly in the epidermis of control but not of
      DHCR24-/- mice. Accordingly, cholesterol was not detected whereas desmosterol was
      abundant in the epidermis of DHCR24-/- mice. Skin histology revealed thickened
      epidermis with few and smaller keratohyaline granules. Aberrant expression of
      keratins such as keratins 6 and 14 suggested hyperproliferative hyperkeratosis
      with undifferentiated keratinocytes throughout the epidermis. Altered expression
      of filaggrin, loricrin, and involcrin were also observed in the epidermis of
      DHCR24-/-. These findings suggested impaired skin barrier function. Indeed,
      increased trans-epidermal water loss and permeability of Lucifer yellow were
      observed in DHCR24-/- mice. DHCR24 thus plays crucial role for skin development
      and its proper function.

PMID- 16410792
TI  - Mitochondrial dynamics in cell life and death.

PMID- 16410791
TI  - Kaposi's sarcoma-associated herpesvirus viremia is associated with the
      progression of classic and endemic Kaposi's sarcoma.
AB  - In order to gain further insight on the role of Kaposi's sarcoma-associated
      herpesvirus (KSHV) in classic and endemic Kaposi's sarcoma (KS) pathogenesis, we
      aimed to determine (i) whether KSHV is detectable in peripheral blood mononuclear
      cells (PBMCs), (ii) which PBMCs subpopulation harbor the virus, (iii) which
      clinical, histologic, and immunologic parameters are associated with KSHV viremia
      in a population of classic and endemic KS. KSHV viremia and various immunologic
      parameters were screened on 81 patients. KSHV viremia was positive in 58% of the
      patients. KSHV was detected in B cells, T cells, and monocytes. CD34+ cells
      depleted in circulating endothelial cells (CECs) were never infected and 50% of
      the patients tested had CECs infected by KSHV. We observed a significant increase
      of IL-2 and IFN-gamma production by CD4 T cells and an increase of IFN-gamma
      production by CD8 T cells compared to control patients. KS progression (P =
      0.001) and KS staging (P = 0.03) were significantly and independently associated
      with positive KSHV viremia. Our results show that there is no specific
      immunosuppression in classic or endemic KS. We showed that KSHV can be detected
      within CECs and that KSHV viremia could be an indicator of circulating mature or
      precursor spindle cells.

PMID- 16410793
TI  - Homotypic FADD interactions through a conserved RXDLL motif are required for
      death receptor-induced apoptosis.
AB  - Death receptors in the TNF receptor superfamily signal for apoptosis via the
      ordered recruitment of FADD and caspase-8 to a death-inducing signaling complex
      (DISC). However, the nature of the protein-protein interactions in the signaling
      complex is not well defined. Here we show that FADD self-associates through a
      conserved RXDLL motif in the death effector domain (DED). Despite exhibiting
      similar binding to both Fas and caspase-8 and preserved overall secondary
      structure, FADD RDXLL motif mutants cannot reconstitute FasL- or TRAIL-induced
      apoptosis and fail to recruit caspase-8 into the DISC of reconstituted FADD
      deficient cells. Abolishing self-association can transform FADD into a dominant
      negative mutant that interferes with Fas-induced apoptosis and formation of
      microscopically visible receptor oligomers. These findings suggest that lateral
      interactions among adapter molecules are required for death receptor apoptosis
      signaling and implicate self-association into oligomeric assemblies as a key
      function of death receptor adapter proteins in initiating apoptosis.

PMID- 16410794
TI  - ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of
      necrotic Ca2+ overload.
AB  - We set out to identify molecular mechanisms underlying the onset of necrotic
      Ca(2+) overload, triggered in two epithelial cell lines by oxidative stress or
      metabolic depletion. As reported earlier, the overload was inhibited by
      extracellular Ca(2+) chelation and the cation channel blocker gadolinium.
      However, the surface permeability to Ca(2+) was reduced by 60%, thus discarding a
      role for Ca(2+) channel/carrier activation. Instead, we registered a collapse of
      the plasma membrane Ca(2+) ATPase (PMCA). Remarkably, inhibition of the
      Na(+)/K(+) ATPase rescued the PMCA and reverted the Ca(2+) rise. Thermodynamic
      considerations suggest that the Ca(2+) overload develops when the Na(+)/K(+)
      ATPase, by virtue of the Na(+) overload, clamps the ATP phosphorylation potential
      below the minimum required by the PMCA. In addition to providing the mechanism
      for the onset of Ca(2+) overload, the crosstalk between cation pumps offers a
      novel explanation for the role of Na(+) in cell death.

PMID- 16410795
TI  - Bioenergetic analysis of cerebellar granule neurons undergoing apoptosis by
      potassium/serum deprivation.
AB  - Apoptosis induced by K+/serum deprivation (low K+) in cerebellar granule neurons
      has been extensively investigated. The mitochondria play a key role in apoptosis
      by releasing proapoptotic factors into the cytoplasm, and mitochondrial
      dysfunction has been proposed as an early or initiating event in this model. To
      directly test this hypothesis, cellular and mitochondrial bioenergetics were
      quantified by determining the respiratory parameters of coverslip-attached
      neurons. While oxidative phosphorylation rate decreased 39-49% in low K+, this
      was due to decreased cellular ATP demand rather than impaired ATP/ADP exchange or
      respiratory chain inhibition. From 3 to 5 h in low K+, apoptosis progressed from
      13 to 40% despite no appreciable change in respiratory parameters. Changes in
      steady-state O2-, assessed with dihydroethidium, were seen in granule but not
      hippocampal neurons. The O2- change correlated with changes in [Ca2+]c, but not
      mitochondrial respiration. Thus, early mitochondrial dysfunction can be excluded
      in this common model of neuronal apoptosis.

PMID- 16410796
TI  - TLR signaling.
AB  - The Toll-like receptor (TLR) family plays an instructive role in innate immune
      responses against microbial pathogens, as well as the subsequent induction of
      adaptive immune responses. TLRs recognize specific molecular patterns found in a
      broad range of microbial pathogens such as bacteria and viruses, triggering
      inflammatory and antiviral responses and dendritic cell maturation, which result
      in the eradication of invading pathogens. Individual TLRs interact with different
      combinations of adapter proteins and activate various transcription factors such
      as nuclear factor (NF)-kappaB, activating protein-1 and interferon regulatory
      factors, driving a specific immune response. This review outlines the recent
      advances in our understanding of TLR-signaling pathways and their roles in immune
      responses. Further, we also discuss a new concept of TLR-independent mechanisms
      for recognition of microbial pathogens.

PMID- 16410797
TI  - ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell
      lung cancer cells through beta1 integrin-dependent activation of PI3-kinase.
AB  - The emergence of resistance to chemotherapy remains a principle problem in the
      treatment of small-cell lung cancer (SCLC). We demonstrate that extracellular
      matrix (ECM) activates phosphatidyl inositol 3-kinase (PI3-kinase) signaling in
      SCLC cells and prevents etoposide-induced caspase-3 activation and subsequent
      apoptosis in a beta1 integrin/PI3-kinase-dependent manner. Crucially we show that
      etoposide and radiation induce G2/M cell cycle arrest in SCLC cells prior to
      apoptosis and that ECM prevents this by overriding the upregulation of
      p21(Cip1/WAF1) and p27(Kip1) and the downregulation of cyclins E, A and B. These
      effects are abrogated by pharmacological and genetic inhibition of PI3-kinase
      signaling. Importantly we show that chemoprotection is not mediated by altered
      SCLC cell proliferation or DNA repair. Thus, ECM via beta1 integrin-mediated PI3
      kinase activation overrides treatment-induced cell cycle arrest and apoptosis,
      allowing SCLC cells to survive with persistent DNA damage, providing a model to
      account for the emergence of acquired drug resistance.

PMID- 16410798
TI  - The crucial role of neuronal plasticity in pain and cell death.

PMID- 16410799
TI  - The TRAF3-binding site of human molluscipox virus FLIP molecule MC159 is critical
      for its capacity to inhibit Fas-induced apoptosis.
AB  - Members of the viral Flice/caspase-8 inhibitory protein (v-FLIP) family prevent
      induction of apoptosis by death receptors through inhibition of the processing
      and activation of procaspase-8 and -10 at the level of the receptor-associated
      death-inducing signaling complex (DISC). Here, we have addressed the molecular
      function of the v-FLIP member MC159 of the human molluscum contagiosum virus.
      MC159 FLIP powerfully inhibited both caspase-dependent and caspase-independent
      cell death induced by Fas. The C-terminal region of MC159 bound TNF receptor
      associated factor (TRAF)3, was necessary for optimal TRAF2 binding, and mediated
      the recruitment of both TRAFs into the Fas DISC. TRAF-binding-deficient mutants
      of MC159 showed impaired inhibition of FasL-induced caspase-8 processing and Fas
      internalization, and had reduced antiapoptotic activity. Our findings provide
      evidence that a MC159/TRAF2/TRAF3 complex regulates a new aspect of Fas
      signaling, and identify MC159 FLIP as a molecule that targets multiple features
      of Fas-induced cell death.

PMID- 16410800
TI  - Differential susceptibility to TRAIL of normal versus malignant human urothelial
      cells.
AB  - Comparing normal human urothelial (NHU) cells to a panel of six representative
      urothelial cell carcinoma (UCC)-derived cell lines, we showed that while TRAIL
      receptor expression patterns were similar, susceptibility to soluble recombinant
      crosslinked TRAIL fell into three categories. 4/6 carcinoma lines were sensitive,
      undergoing rapid and extensive death; NHU and 253J cells were partially resistant
      and HT1376 cells, like normal fibroblasts, were refractory. Both normal and
      malignant urothelial cells underwent apoptosis via the same caspase-8/9-mediated
      mechanism. Rapid receptor downregulation was a mechanism for evasion by some UCC
      cells. TRAIL resistance in malignant urothelial cells was partially dependent on
      FLIP(L) and was differentially mediated by p38(MAPK), whereas in normal cells,
      resistance was mediated by NF-kappaB. Importantly, extensive killing of UCC cells
      could be induced using noncrosslinked TRAIL after prolonged exposure, with no
      damage to their homologous, normal urothelial cell counterparts.

PMID- 16410801
TI  - Controlling NF-kappaB activation in T cells by costimulatory receptors.
AB  - Full and productive activation of T lymphocytes relies on the simultaneous
      delivery of T cell receptor (TCR)- and coreceptor-derived signals. In naive T
      cells engagement of the TCR alone causes anergy, while TCR triggering of
      preactivated T cells results in activation-induced cell death. Costimulatory
      signals are prominently mirrored by the activation of NF-kappaB, which needs
      input from the TCR as well as from coreceptors in order to be fully activated and
      to fulfil its crucial function in the immune response. Coreceptor-generated
      signals tightly control the duration and amplitude of the NF-kappaB response. The
      activation of IkappaB kinase (IKK) complex at the contact zone between a T cell
      and an antigen-presenting cell offers the unique opportunity to study the spatial
      organization of IKK activation. Recent studies indicate that coreceptor pathways
      influence the threshold activities of many signalling mediators and thus act on
      multiple layers of the NF-kappaB pathway.

PMID- 16410802
TI  - Signals from within: the DNA-damage-induced NF-kappaB response.
AB  - An appropriate response to genotoxic stress is essential for maintenance of
      genome stability and avoiding the passage to neoplasia. Nuclear factor kappaB (NF
      kappaB) is activated as part of the DNA damage response and is thought to
      orchestrate a cell survival pathway, which, together with the activation of cell
      cycle checkpoints and DNA repair, allows the cell in cases of limited damage to
      restore a normal life cycle, unharmed. In this respect, NF-kappaB is one of the
      main factors accounting for chemotherapy resistance and as such impedes effective
      cancer treatment, representing an important drug target. Despite this high
      clinical relevance, signalling cascades leading to DNA damage-induced NF-kappaB
      activation are poorly understood and the use of highly divergent experimental set
      ups in the past led to many controversies in the field. Therefore, in this
      review, we will try to summarize the current knowledge of distinct DNA damage
      induced NF-kappaB signalling pathways.

PMID- 16410803
TI  - Good cop, bad cop: the different faces of NF-kappaB.
AB  - Complexes formed from the nuclear factor kappaB (NF-kappaB) family of
      transcription factors are ubiquitously expressed and are induced by a diverse
      array of stimuli. This results in their becoming activated in a wide variety of
      different settings. While the functions of NF-kappaB in many of these contexts
      have been the subject of intense research and are now well established, it is
      also clear that there is great diversity in the effects and consequences of NF
      kappaB activation. NF-kappaB subunits do not necessarily regulate the same genes,
      in an identical manner, in all of the different circumstances in which they are
      induced. This review will discuss the different functions of NF-kappaB, the
      pathways that modulate NF-kappaB subunit activity and, in contrast to its more
      commonly thought of role as a promoter of cancer cell growth and survival, the
      ability of NF-kappaB, under some circumstances, to behave as a tumor suppressor.

PMID- 16410804
TI  - Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12
      cells.
AB  - The mechanisms of peroxynitrite-induced apoptosis are not fully understood. We
      report here that peroxynitrite-induced apoptosis of PC12 cells requires the
      simultaneous activation of p38 and JNK MAP kinase, which in turn activates the
      intrinsic apoptotic pathway, as evidenced by Bax translocation to the
      mitochondria, cytochrome c release to the cytoplasm and activation of caspases,
      leading to cell death. Peroxynitrite induces inactivation of the Akt pathway.
      Furthermore, overexpression of constitutively active Akt inhibits both
      peroxynitrite-induced Bax translocation and cell death. Peroxynitrite-induced
      death was prevented by overexpression of Bcl-2 and by cyclosporin A, implicating
      the involvement of the intrinsic apoptotic pathway. Selective inhibition of mixed
      lineage kinase (MLK), p38 or JNK does not attenuate the decrease in Akt
      phosphorylation showing that inactivation of the Akt pathway occurs independently
      of the MLK/MAPK pathway. Together, these results reveal that peroxynitrite
      induced activation of the intrinsic apoptotic pathway involves interactions with
      the MLK/MAPK and Akt signaling pathways.

PMID- 16410805
TI  - Defining the mechanism by which IFN-beta dowregulates c-myc expression in human
      melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold
      35).
AB  - Type I interferons (IFN-alpha/-beta) are capable of suppressing c-myc mRNA
      expression by modulating post-transcriptional processing. However, the molecular
      mechanism of this phenomenon is poorly understood. We previously established that
      human polynucleotide phosphorylase (hPNPase(old-35)), a type I IFN-inducible
      3',5' exoribonuclease involved in mRNA degradation, induces G1 cell cycle arrest
      and eventually apoptosis by specifically degrading c-myc mRNA. We now demonstrate
      a close association between IFN-beta-induced hPNPase(old-35) upregulation and c
      myc downregulation in human melanoma cells. Employing stable melanoma cell clones
      expressing hPNPase(old-35) small inhibitory RNA, we demonstrate that hPNPase(old
      35) is a key molecule coupled with IFN-beta-mediated downregulation of c-myc
      mRNA. Inhibition of hPNPase(old-35) or overexpression of c-myc protects melanoma
      cells from IFN-beta-mediated growth inhibition, emphasizing the importance of
      hPNPase(old-35) upregulation and consequent c-myc downregulation in IFN-beta
      induced growth inhibition and apoptosis induction. In these contexts, targeted
      overexpression of hPNPase(old-35) might be a novel therapeutic strategy for c-myc
      overexpressing and IFN-resistant tumors, such as melanomas.

PMID- 16410807
TI  - Closure of macular hole following vitrectomy for diabetic tractional macular
      detachment.

PMID- 16410806
TI  - FGF-2 overexpression opposes the beta amyloid toxic injuries to the vascular
      endothelium.
AB  - Recent evidences suggest that Abeta peptides modulate endothelial cell (EC)
      functions. At low concentrations, Abeta1-40 enhances the pro-angiogenic activity
      of FGF-2, whereas deposition of excess Abeta causes EC dysfunction and cerebral
      amyloid angiopathy (CAA). We investigated whether FGF-2 attenuates EC dysfunction
      caused by pathological Abeta levels. We studied Abeta1-40 on EC survival, as well
      as on signals responsible of their angiogenic phenotype. At 5-50 microM Abeta1-40
      reduced EC population, caused apoptosis, downregulated FGF-2 production,
      inhibited FGF-2 binding to heparin, and FGFR1 phosphorylation. Toxic effects were
      owing to lack of FGF-2 stimulation, as EC overexpressing FGF-2 displayed
      extraordinary resistance to Abeta1-40 injuries. The FGF-2 mechanism responsible
      for reversing damages, involves the downstream enhancement of Akt, a pathway
      independent of eNOS activation. In conclusion, we demonstrate that FGF-2 protects
      EC from the effects of excess Abeta1-40, suggesting that it may attenuate the
      consequences of Abeta deposition in pathologies as CAA.

PMID- 16410808
TI  - Viscogonioplasty: an effective procedure for lowering intraocular pressure in
      primary angle closure glaucoma.
AB  - PURPOSE: To evaluate the safety and intraocular pressure (IOP) lowering effect of
      combined phacoemulsification and viscogonioplasty (Phaco-VGP) in managing primary
      acute closed-angle glaucoma (ACAG) unresponsive to conventional therapy (patent
      PI). PATIENT AND METHODS: In all, 15 consecutive eyes of patients with refractory
      ACAG and greater than 270 degrees peripheral anterior synechiae (PAS) underwent
      VGP. The technique of VGP involved routine phacoemulsification with intraocular
      lens implantation (Phaco/IOL) under topical anaesthetic. Following IOL
      implantation a heavy viscoelastic was used to deepen the anterior chamber and
      then injected near the angle for 360 degrees (without touching the trabecular
      meshwork) to break the PAS. No surgical instrument was used to physically break
      the PAS. Upon completion of VGP, automated irrigation with balanced salt solution
      to remove the viscoelastic was performed. RESULTS: Mean IOP reduced from 52.1 to
      14.1 mmHg by Phaco-VGP at 6-months review. 14/15 patients were free of glaucoma
      medications at 6-month review. All angles showed exposure of the trabecular
      meshwork over 360 degrees postoperatively without evidence of residual synechiae.
      No untoward complications were observed in any patient. CONCLUSION: VGP may have
      a role in controlling IOP effectively and safely in patients with refractory
      ACAG. It produces a large drop in the IOP and opening of the angle. It is a
      relatively simple technique to learn and we would recommend its use in the eyes
      of all patients who have had ACAG and are undergoing cataract extraction.

PMID- 16410809
TI  - Follow-up after intravitreal triamcinolone acetonide for exudative age-related
      macular degeneration.
AB  - PURPOSE: To report on the follow-up of patients who received an intravitreal
      triamcinolone acetonide injection (IVTA) as treatment of exudative age-related
      macular degeneration. METHODS: The clinical interventional case-series study
      included 205 patients (222 eyes) with progressive exudative age-related macular
      degeneration with subfoveal neovascularization who consecutively received an IVTA
      of about 20 mg as only therapeutic procedure and for whom follow-up was at least
      3 months. Mean follow-up was 10.4+/-7.1 months (range, 3-35.7 months). RESULTS:
      Visual acuity improved significantly (P<0.001) from baseline (0.90+/-0.45
      logarithm of the minimum angle of resolution (LogMar)) to a mean minimum of
      0.79+/-0.42 LogMar during follow-up. In 86 (38.7%) eyes and in 55 (24.8%) eyes,
      best visual acuity increased by at least two and three Snellen lines,
      respectively. Comparing the measurements at specific postinjection examination
      dates showed that visual acuity measurements taken at 1, 2, and 3 months after
      injection were not significantly different from the baseline value. Measurements
      taken at 6, 9, and 12 months after the injection were significantly (P<0.001)
      lower than the measurements at baseline. Mean loss at 6 months was 1.4+/-3.8
      Snellen lines, at 9 months, 2.5+/-4.6 lines, and at 12 months after the
      injection, 2.6+/-4.0 lines. Intraocular pressure increased significantly
      (P<0.001) during the first 6 months, and returned to baseline at 9 months after
      injection. CONCLUSIONS: Single injection high-dosage IVTA did not show an
      apparent benefit at 12 months after injection in patients with neovascular age
      related macular degeneration.

PMID- 16410810
TI  - Bilateral stellar neuroretinitis in a patient with dengue fever.

PMID- 16410811
TI  - Assisted conception and retinopathy of prematurity: 8-year follow-up study.
AB  - AIMS: To assess the effect of assisted conception (AC) on retinopathy of
      prematurity (ROP) and ROP screening. Follow-up to the study by McKibbin et al.
      METHODS: Retrospective study utilising computerised databases of ROP screening,
      live births, AC and multiple births between 1st April 2000 and 31st August 2003
      at St James's Hospital (SJUH) Leeds. chi(2) tests of significance were used.
      RESULTS: ROP screening was undertaken in 11/265 (4.2%) of AC births versus 1.6%
      of all SJUH births. This is significantly less than the 20.3% of AC babies
      screened in McKibbin et al study (P=<0.01). There was no ROP detected in the 11
      AC babies. Of all AC births, 36.9% were one of twins and 1.5% from triplet births
      compared to 46.0% one of twins and 18.6% one of triplets in McKibbin's study.
      CONCLUSIONS: The percentage of AC babies requiring ROP screening has fallen since
      McKibbin et al study which was performed between August 1991 and December 1994.
      This appears to be at least partially due to the reduced multiple birth rates.
      This reduction in the multiple birth rates follows evidence that reducing the
      number of embryos transferred does not reduce the number of couples taking home a
      baby and Human Fertility and Embryology Association guidelines recommending 'no
      more than two embryos should be transferred in an IVF cycle'. Changes in clinical
      practice at SJUH have significantly reduced the likelihood of AC babies requiring
      ROP screening and developing ROP.

PMID- 16410812
TI  - Risk evaluation of outcome of vitreous surgery based on vitreous levels of
      cytokines.
AB  - AIM: To ascertain whether vitreous and plasma levels of vascular endothelial
      growth factor (VEGF), interleukin-6 (IL-6) and fundus findings could predict the
      outcome of vitreous surgery in patients with proliferative diabetic retinopathy
      (PDR). METHODS: Vitreous fluid samples were obtained during vitreoretinal surgery
      from 73 consecutive eyes with PDR. The levels of VEGF and IL-6 in vitreous fluid
      and plasma were determined by enzyme-linked immunosorbent assay. Patients were
      prospectively followed for 6 months and the postoperative outcome was analysed by
      logistic regression analysis. RESULTS: No improvement and/or progression of PDR
      occurred in 23 (32%) of the 73 eyes (progression group). The vitreous levels of
      VEGF and IL-6 were significantly higher in eyes from the progression group than
      in eyes with regression of PDR (regression group) (P=0.0032 and 0.0088,
      respectively). Multivariate logistic regression analysis showed that higher
      vitreous levels of VEGF were associated with the progression of PDR after
      vitreous surgery (odds ratio 2.72, P=0.0003). CONCLUSIONS: High vitreous levels
      of VEGF identified as a significant risk factor for the outcome of vitreous
      surgery in patients with PDR. A model was developed to predict the probability of
      PDR progression and measurement of the vitreous level of VEGF may be useful for
      predicting the outcome of surgery.

PMID- 16410813
TI  - Masked orbital abscess in Wegener's granulomatosis.
AB  - Two patients with chronic Wegener's granulomatosis presented with worsening
      proptosis and visual acuity. Both patients had been maintained on long-term
      corticosteroids, which led to masking of the signs of orbital sepsis with
      potentially life-threatening implications.

PMID- 16410814
TI  - Bilateral acute retinal necrosis syndrome following herpes simplex type 1
      encephalitis.

PMID- 16410815
TI  - Effect of highly active antiretroviral therapy (HAART) on the natural history of
      ocular manifestations in HIV-infected children.
AB  - PURPOSE: To determine the effect of highly active antiretroviral therapy (HAART)
      on the natural history of ocular manifestations in HIV-infected children.
      METHODS: All of the HIV-infected children attending the Institute of Pediatrics,
      University of Milan, Milan, Italy, between 1982 and 2004 were studied. Every 3
      months, they were physically examined and underwent indirect fundoscopy conducted
      by an experienced ophthalmologist; if diagnosed as having eye disease, they were
      evaluated by the ophthalmologist every week while on specific therapy and monthly
      thereafter. The clinical and laboratory findings before and after the
      introduction of HAART were compared. RESULTS: The cohort consisted of 117 HIV
      infected children (61 males), with a follow-up ranging from 0.09 to 22.31 years
      (median, 16.33 years). A total of nine cases of ocular involvement (7.7%) were
      diagnosed between 1983 and 1994, before the introduction of HAART. All nine
      children died 4-24 months (median, 15 months) after the diagnosis of ophthalmic
      disease. No case of ocular involvement was observed after the introduction of
      HAART (P=0.011 vs. before HAART). CONCLUSION: The introduction of HAART has had a
      significant impact on the natural history of ocular manifestations in HIV
      infected children, thus suggesting that a reduction in the frequency of
      ophthalmologic follow-up should be considered for HAART-treated HIV-infected
      children with immune reconstitution and no visual symptom.

PMID- 16410816
TI  - The complement system and age-related macular degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness
      in the developed world. There are increasing evidences to suggest the complement
      system may play a significant role on the pathogenesis of AMD. In this review, we
      summarise the current research in this area. METHODS: Review of literature.
      RESULTS: The complement system is a complex system with several activation
      pathways. Complement factor H (CFH) polymorphisms has been associated with
      increase risk of AMD. CFH is an inhibitor protein; the polymorphisms might cause
      uncontrolled activation by initiation events. CONCLUSION: Further studies on the
      molecular basis of the complement-mediated pathogenesis of AMD may offer novel
      therapy to AMD.

PMID- 16410817
TI  - The subluxated lens: a patient's perspective.

PMID- 16410818
TI  - Proton beam therapy for iris melanoma: a review of 15 cases.
AB  - AIM: To report results of proton beam therapy for iris melanoma. METHODS: A
      retrospective case series of 15 patients with nonresectable iris melanomas
      treated with proton beam therapy between August 1998 and August 2004. The main
      outcome measures were (1) local tumour control, (2) complications, and (3) eye
      retention. RESULTS: Of the 15 cases, 11 patients showed documented growth
      (including two cases of local recurrence following iridocyclectomy) while a
      further three cases were biopsy-proven melanoma. One patient presented with a
      newly acquired vascular nodule of the iris associated with angle seeding and
      glaucoma. Tumour control at mean follow-up of 34 months was 93% (14 of 15 eyes).
      Common complications included glaucoma in 53% (five patients had glaucoma prior
      to irradiation), dry eye (27%) and cataract in three patients (20%). Eye
      retention was possible in 80% (12 cases). CONCLUSION: Proton beam therapy is an
      effective treatment for cases of nonresectable iris melanoma. The major
      complications are cataract and glaucoma.

PMID- 16410819
TI  - Employment of liver tissue slice analysis to assay hepatotoxicity linked to
      replicative and nonreplicative adenoviral agents.
AB  - Whereas virotherapy has emerged as a novel and promising approach for neoplastic
      diseases, appropriate model systems have hampered preclinical evaluation of
      candidate conditionally replicative adenovirus agents (CRAds) with respect to
      liver toxicity. This is due to the inability of human viral agents to cross
      species. We have recently shown the human liver tissue slice model to be a facile
      means to validate adenoviral replication. On this basis, we sought to determine
      whether our ex vivo liver tissue slice model could be used to assess CRAd
      mediated liver toxicity. We analyzed and compared the toxicity of a conditionally
      replicative adenovirus (AdDelta24) to that of a replication incompetent
      adenovirus (Adnull [E1-]) in mouse and human liver tissue slices. To accomplish
      this, we examined the hepatic apoptosis expression profile by DNA microarray
      analyses, and compared these results to extracellular release of aminotransferase
      enzymes, along with direct evidence of apoptosis by caspase-3 immunhistochemical
      staining and TUNEL assays. Human and mouse liver tissue slices demonstrated a
      marked increase in extracellular release of aminotransferase enzymes on infection
      with AdDelta24 compared to Adnull. AdDelta24-mediated liver toxicity was further
      demonstrated by apoptosis induction, as detected by caspase-3 immunohistochemical
      staining, TUNEL assay and microarray analysis. In conclusion, concordance of CRAd
      mediated apoptosis in both the human and the mouse liver tissue slice models was
      demonstrated, despite the limited replication ability of CRAds in mouse liver
      slices. The results of this study, defining the CRAd-mediated apoptosis gene
      expression profiles in human and mouse liver, may lay a foundation for
      preclinical liver toxicity analysis of CRAd agents.

PMID- 16410821
TI  - Suppression of EGFR expression by antisense or small interference RNA inhibits
      U251 glioma cell growth in vitro and in vivo.
AB  - Epidermal growth factor receptor (EGFR) had been reported as one of the major
      responsible genes for malignant progression and phenotype reversion of gliomas,
      and has been used as one of the most important therapeutic targets. In the
      present study, small interference RNA (siRNA) and antisense EGFR expression
      constructs, which target sequences of human EGFR catalytic domain (2400-2420) and
      the 3'-coding region, respectively, were used to examine the growth inhibition
      effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M
      arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix
      demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected
      U251 cells, indicating poor cell growth activities. In addition, the tumor
      volumes in U251 subcutaneous mice model treated with antisense and siRNA were
      significantly smaller than those treated with control siRNA and phosphate
      buffered saline. Also, glial fibrillary acidic protein expression was upregulated
      in antisense- and siRNA-treated groups than the control groups. Our results
      demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can
      inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in
      vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy
      would be a new strategy in treatment of gliomas.

PMID- 16410820
TI  - Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1
      and AQ4N.
AB  - Drug metabolizing transgene products, which activate bioreductive cytotoxins, can
      be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is
      bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4.
      Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6
      transgenes with AQ4N and radiation inhibits tumor growth. Here we examine the
      ability of other CYPs, in particular CYP1A1, to metabolize AQ4N, and to enhance
      radiosensitization. Metabolism of AQ4N was assessed using microsomes prepared
      from baculovirus-infected cells transfected with various CYP isoforms. AQ4N
      metabolism was most efficient with CYP1A1 (66.7 nmol/min/pmol) and 2B6 (34.4
      nmol/min/pmol). Transient transfection of human CYP1A1+/-CYP reductase (CYPRED)
      was investigated in hypoxic RIF-1 mouse cells in vitro using the alkaline comet
      assay. There was a significant increase in DNA damage following transient
      transfection of CYP1A1 compared to non-transfected cells; inclusion of CYPRED
      provided no additional effect. In vivo, a single intra-tumoral injection of a
      CYP1A1 construct in combination with AQ4N (100 mg/kg i.p.) and 20 Gy X-rays
      caused a 16-day delay in tumor regrowth compared to tumors receiving AQ4N plus
      radiation and empty vector (P=0.0344). The results show the efficacy of a CYP1A1
      mediated GDEPT strategy for bioreduction of AQ4N.

PMID- 16410822
TI  - Clinical trials of gene therapy, virotherapy, and immunotherapy for malignant
      gliomas.
AB  - Despite advances in surgical and adjuvant therapy, the prognosis for malignant
      gliomas remains dismal. This gloomy scenario has been recently brightened by the
      increasing understanding of the genetic and biological mechanisms at the basis of
      brain tumor development. These findings are being translated into innovative
      therapeutic approaches, including gene therapy, virotherapy, and vaccination,
      some of which have already been experimented in clinical trials. The advantages
      and disadvantages of all these different therapeutic modalities for malignant
      gliomas will be critically discussed, providing perspective for future
      investigations.

PMID- 16410824
TI  - An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular
      carcinoma and colon cancer that express alpha-fetoprotein.
AB  - Antitumor vaccination therapies using attenuated Salmonella typhimurium carrying
      plasmid DNA encoding tumor-associated antigens are currently under preclinical
      development. In the present study, we first established a useful method to
      facilitate in vivo monitoring of attenuated S. typhimurium uptake using a
      bioluminescent lux gene operon plasmid. Following transformation with the lux
      gene operon construct, mice were fed with various amounts of attenuated S.
      typhimurium-lux to monitor in vivo clearance over a period of 24 h. We found that
      the ingested attenuated S. typhimurium-lux cells were almost cleared out 9 h
      postfeeding, as judged by a significant decrease in bioluminescence. We further
      examined the therapeutic efficacy of vaccination using attenuated S. typhimurium
      carrying the mouse alpha-fetoprotein (AFP) gene against a cancer line CT26-murine
      alpha-feto protein (mAFP) that stably expresses AFP and mouse hepatocellular
      carcinoma (HCC) Hepa1-6. Attenuated S. typhimurium oral DNA vaccine was found to
      promote protective immunity against both CT26-mAFP and Hepa1-6 tumor cells
      growth. The oral DNA vaccine significantly increased the life span of tumor
      challenged mice in both tumor models. Together, these results suggest that
      vaccination with the attenuated S. typhimurium oral DNA vaccine that carries the
      AFP gene could be a promising strategy to prevent HCC development.

PMID- 16410825
TI  - Inhibition of angiogenesis and tumor progression by hydrodynamic cotransfection
      of angiostatin K1-3, endostatin, and saxatilin genes.
AB  - In vivo expression of angiostatin and endostatin, two different types of
      endothelial cell growth inhibitor, have been reported to inhibit vascularization
      in tumor tissues, resulting in tumor growth inhibition. Recently, in vivo
      expression of saxatilin, a novel disintegrin purified from snake (Gloydius
      saxatilis) venom, was able to strongly inhibit endothelial cell proliferation and
      smooth muscle cell migration, resulting in tumor growth inhibition. However, the
      antitumor efficacy of the individual antiangiogenic molecules expressed in vivo
      was not sufficiently potent to induce tumor regression in animal models.
      Therefore, in this study, we have systemically examined how combinational
      transfer of angiostatin, endostatin, and saxatilin genes affects
      neovascularization in tumor tissues and tumor progression in a mouse model. In
      Matrigel-implanted mice, cotransfection with plasmids encoding angiostatin K1-3
      (pFLAG-Angio K1/3), endostatin (pFLAG-Endo), and saxatilin (pFLAG-Sax) resulted
      in the most effective inhibition of angiogenesis. In addition, hydrodynamic
      cotransfection of the three genes induced more inhibition of B16BL6 melanoma
      growth and pulmonary metastasis than other combinations of transfected genes.
      Compared with the empty vector-treated control group, cotreatment with the three
      plasmids reduced B16BL6 tumor growth by 89% and pulmonary metastasis by 90%.
      These results provide additional evidence supporting the combined systemic
      expression of antiangiogenic factors, such as angiostatin K1-3, endostatin, and
      saxatilin, as an alternative procedure for antiangiogenic cancer therapy.

PMID- 16410823
TI  - Gene therapy for carcinoma of the breast.
AB  - In view of the limited success of available treatment modalities for breast
      cancer, alternative and complementary strategies need to be developed. The
      delineation of the molecular basis of breast cancer provides the possibility of
      specific intervention by gene therapy through the introduction of genetic
      material for therapeutic purposes. In this regard, several gene therapy
      approaches for carcinoma of the breast have been developed. These approaches can
      be divided into six broad categories: (1) mutation compensation, (2) molecular
      chemotherapy, (3) proapoptotic gene therapy, (4) antiangiogenic gene therapy, (5)
      genetic immunopotentiation, and (6) genetic modulation of resistance/sensitivity.
      Clinical trials for breast cancer have been initiated to evaluate safety,
      toxicity, and efficacy. Combined modality therapy with gene therapy and
      chemotherapy or radiation therapy has shown promising results. It is expected
      that as new therapeutic targets and approaches are identified and advances in
      vector design are realized, gene therapy will play an increasing role in clinical
      breast cancer treatment.

PMID- 16410826
TI  - Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in
      advanced-stage non-small-cell lung cancer.
AB  - Tumor vaccines composed of autologous tumor cells genetically modified to secrete
      granulocyte-macrophage colony-stimulating factor (GM-CSF) (GVAX) have
      demonstrated clinical activity in advanced-stage non-small-cell lung cancer
      (NSCLC). In an effort to remove the requirement for genetic transduction of
      individual tumors, we developed a 'bystander' GVAX platform composed of
      autologous tumor cells mixed with an allogeneic GM-CSF-secreting cell line. We
      conducted a phase I/II trial of this vaccine (3-12 biweekly vaccinations) in
      advanced-stage NSCLC. Tumors were harvested from 86 patients, tumor cell
      processing was successful in 76, and 49 proceeded to vaccination. The most common
      toxicity was local vaccine injection site reactions. Serum GM-CSF
      pharmacokinetics were consistent with secretion of GM-CSF from vaccine cells for
      up to 4 days with associated transient leukocytosis confirming the bioactivity of
      vaccine-secreted GM-CSF. Evidence of vaccine-induced immune activation was
      demonstrated; however, objective tumor responses were not seen. Compared with
      autologous GVAX vaccines prepared by transduction of individual tumors with an
      adenoviral GM-CSF vector, vaccine GM-CSF secretion was approximately 25-fold
      higher with the bystander GVAX vaccine used in this trial. However, the frequency
      of vaccine site reactions, tumor response, time to disease progression, and
      survival were all less favorable in the current study.

PMID- 16410827
TI  - The Notch ligand JAG1 is required for sensory progenitor development in the
      mammalian inner ear.
AB  - In mammals, six separate sensory regions in the inner ear are essential for
      hearing and balance function. Each sensory region is made up of hair cells, which
      are the sensory cells, and their associated supporting cells, both arising from a
      common progenitor. Little is known about the molecular mechanisms that govern the
      development of these sensory organs. Notch signaling plays a pivotal role in the
      differentiation of hair cells and supporting cells by mediating lateral
      inhibition via the ligands Delta-like 1 and Jagged (JAG) 2. However, another
      Notch ligand, JAG1, is expressed early in the sensory patches prior to cell
      differentiation, indicating that there may be an earlier role for Notch signaling
      in sensory development in the ear. Here, using conditional gene targeting, we
      show that the Jag1 gene is required for the normal development of all six sensory
      organs within the inner ear. Cristae are completely lacking in Jag1-conditional
      knockout (cko) mutant inner ears, whereas the cochlea and utricle show partial
      sensory development. The saccular macula is present but malformed. Using SOX2 and
      p27kip1 as molecular markers of the prosensory domain, we show that JAG1 is
      initially expressed in all the prosensory regions of the ear, but becomes down
      regulated in the nascent organ of Corti by embryonic day 14.5, when the cells
      exit the cell cycle and differentiate. We also show that both SOX2 and p27kip1
      are down-regulated in Jag1-cko inner ears. Taken together, these data demonstrate
      that JAG1 is expressed early in the prosensory domains of both the cochlear and
      vestibular regions, and is required to maintain the normal expression levels of
      both SOX2 and p27kip1. These data demonstrate that JAG1-mediated Notch signaling
      is essential during early development for establishing the prosensory regions of
      the inner ear.

PMID- 16410828
TI  - Genome-wide identification of human functional DNA using a neutral indel model.
AB  - It has become clear that a large proportion of functional DNA in the human genome
      does not code for protein. Identification of this non-coding functional sequence
      using comparative approaches is proving difficult and has previously been thought
      to require deep sequencing of multiple vertebrates. Here we introduce a new model
      and comparative method that, instead of nucleotide substitutions, uses the
      evolutionary imprint of insertions and deletions (indels) to infer the past
      consequences of selection. The model predicts the distribution of indels under
      neutrality, and shows an excellent fit to human-mouse ancestral repeat data.
      Across the genome, many unusually long ungapped regions are detected that are
      unaccounted for by the neutral model, and which we predict to be highly enriched
      in functional DNA that has been subject to purifying selection with respect to
      indels. We use the model to determine the proportion under indel-purifying
      selection to be between 2.56% and 3.25% of human euchromatin. Since annotated
      protein-coding genes comprise only 1.2% of euchromatin, these results lend
      further weight to the proposition that more than half the functional complement
      of the human genome is non-protein-coding. The method is surprisingly powerful at
      identifying selected sequence using only two or three mammalian genomes. Applying
      the method to the human, mouse, and dog genomes, we identify 90 Mb of human
      sequence under indel-purifying selection, at a predicted 10% false-discovery rate
      and 75% sensitivity. As expected, most of the identified sequence represents
      unannotated material, while the recovered proportions of known protein-coding and
      microRNA genes closely match the predicted sensitivity of the method. The
      method's high sensitivity to functional sequence such as microRNAs suggest that
      as yet unannotated microRNA genes are enriched among the sequences identified.
      Furthermore, its independence of substitutions allowed us to identify sequence
      that has been subject to heterogeneous selection, that is, sequence subject to
      both positive selection with respect to substitutions and purifying selection
      with respect to indels. The ability to identify elements under heterogeneous
      selection enables, for the first time, the genome-wide investigation of positive
      selection on functional elements other than protein-coding genes.

PMID- 16410829
TI  - Long-range periodic patterns in microbial genomes indicate significant multi
      scale chromosomal organization.
AB  - Genome organization can be studied through analysis of chromosome position
      dependent patterns in sequence-derived parameters. A comprehensive analysis of
      such patterns in prokaryotic sequences and genome-scale functional data has yet
      to be performed. We detected spatial patterns in sequence-derived parameters for
      163 chromosomes occurring in 135 bacterial and 16 archaeal organisms using
      wavelet analysis. Pattern strength was found to correlate with organism-specific
      features such as genome size, overall GC content, and the occurrence of known
      motility and chromosomal binding proteins. Given additional functional data for
      Escherichia coli, we found significant correlations among chromosome position
      dependent patterns in numerous properties, some of which are consistent with
      previously experimentally identified chromosome macrodomains. These results
      demonstrate that the large-scale organization of most sequenced genomes is
      significantly nonrandom, and, moreover, that this organization is likely linked
      to genome size, nucleotide composition, and information transfer processes.
      Constraints on genome evolution and design are thus not solely dependent upon
      information content, but also upon an intricate multi-parameter, multi-length
      scale organization of the chromosome.

PMID- 16410830
TI  - A review of knee dislocations.
AB  - OBJECTIVE: To inform health care professionals about the various mechanisms of
      this little-known injury, as well as its potentially limb-threatening
      complications. In addition, keys to immediate recognition and the importance of a
      thorough rehabilitation program are stressed. DATA SOURCES: I searched MEDLINE
      (1966-2000) using the key words knee dislocation, knee injury, and tibiofemoral
      dislocation. DATA SYNTHESIS: Knee dislocations are uncommon but very serious
      injuries. Because the joint may spontaneously reduce before the examiner reaches
      the patient, the examiner must be aware of the potential complications and rule
      out any neurovascular damage immediately. CONCLUSIONS/RECOMMENDATIONS: Prompt
      recognition of this injury and proper care combined with an extensive
      rehabilitation program can greatly improve the prognosis for the patient.
      Neurovascular integrity should be assessed routinely for several days after the
      injury to ensure that complications do not develop.

PMID- 16410831
TI  - Independent degeneration of photoreceptors and retinal pigment epithelium in
      conditional knockout mouse models of choroideremia.
AB  - Choroideremia (CHM) is an X-linked degeneration of the retinal pigment epithelium
      (RPE), photoreceptors, and choroid, caused by loss of function of the CHM/REP1
      gene. REP1 is involved in lipid modification (prenylation) of Rab GTPases, key
      regulators of intracellular vesicular transport and organelle dynamics. To study
      the pathogenesis of CHM and to develop a model for assessing gene therapy, we
      have created a conditional mouse knockout of the Chm gene. Heterozygous-null
      females exhibit characteristic hallmarks of CHM: progressive degeneration of the
      photoreceptors, patchy depigmentation of the RPE, and Rab prenylation defects.
      Using tamoxifen-inducible and tissue-specific Cre expression in combination with
      floxed Chm alleles, we show that CHM pathogenesis involves independently
      triggered degeneration of photoreceptors and the RPE, associated with different
      subsets of defective Rabs.

PMID- 16410832
TI  - Leptin neutralization interferes with pathogenic T cell autoreactivity in
      autoimmune encephalomyelitis.
AB  - Recent evidence has indicated that leptin, an adipocyte-secreted hormone
      belonging to the helical cytokine family, significantly influences immune and
      autoimmune responses. We investigate here the mechanisms by which in vivo
      abrogation of leptin effects protects SJL/J mice from proteolipid protein peptide
      PLP(139-151)-induced EAE, an animal model of MS. Blockade of leptin with anti
      leptin Abs or with a soluble mouse leptin receptor chimera (ObR:Fc), either
      before or after onset of EAE, improved clinical score, slowed disease
      progression, reduced disease relapses, inhibited PLP(139-151)-specific T cell
      proliferation, and switched cytokine secretion toward a Th2/regulatory profile.
      This was also confirmed by induction of forkhead box p3 (Foxp3) expression in CD4
      T cells in leptin-neutralized mice. Importantly, anti-leptin treatment induced a
      failure to downmodulate the cyclin-dependent kinase inhibitor p27 (p27) in
      autoreactive CD4 T cells. These effects were associated with increased tyrosine
      phosphorylation of both ERK1/2 and STAT6. Taken together, our data provide what
      we believe is a new molecular basis for leptin antagonism in EAE and envision
      novel strategies of leptin-based molecular targeting in the disease.

PMID- 16410833
TI  - Type 3 deiodinase is critical for the maturation and function of the thyroid
      axis.
AB  - Developmental exposure to appropriate levels of thyroid hormones (THs) in a
      timely manner is critical to normal development in vertebrates. Among the factors
      potentially affecting perinatal exposure of tissues to THs is type 3 deiodinase
      (D3). This enzyme degrades THs and is highly expressed in the pregnant uterus,
      placenta, and fetal and neonatal tissues. To determine the physiological role of
      D3, we have generated a mouse D3 knockout model (D3KO) by a targeted inactivating
      mutation of the Dio3 gene in mouse ES cells. Early in life, D3KO mice exhibit
      delayed 3,5,3'-triiodothyronine (T3) clearance, a markedly elevated serum T3
      level, and overexpression of T3-inducible genes in the brain. From postnatal day
      15 to adulthood, D3KO mice demonstrate central hypothyroidism, with low serum
      levels of 3,5,3',5'-tetraiodothyronine (T4) and T3, and modest or no increase in
      thyroid-stimulating hormone (TSH) concentration. Peripheral tissues are also
      hypothyroid. Hypothalamic T3 content is decreased while thyrotropin-releasing
      hormone (TRH) expression is elevated. Our results demonstrate that the lack of D3
      function results in neonatal thyrotoxicosis followed later by central
      hypothyroidism that persists throughout life. These mice provide a new model of
      central hypothyroidism and reveal a critical role for D3 in the maturation and
      function of the thyroid axis.

PMID- 16410835
TI  - Metabolic enzymes that bind RNA: yet another level of cellular regulatory
      network?
AB  - Several enzymes that were originally characterized to have one defined function
      in intermediatory metabolism are now shown to participate in a number of other
      cellular processes. Multifunctional proteins may be crucial for building of the
      highly complex networks that maintain the function and structure in the
      eukaryotic cell possessing a relatively low number of protein-encoding genes. One
      facet of this phenomenon, on which I will focus in this review, is the
      interaction of metabolic enzymes with RNA. The list of such enzymes known to be
      associated with RNA is constantly expanding, but the most intriguing question
      remains unanswered: are the metabolic enzyme-RNA interactions relevant in the
      regulation of cell metabolism? It has been proposed that metabolic RNA-binding
      enzymes participate in general regulatory circuits linking a metabolic function
      to a regulatory mechanism, similar to the situation of the metabolic enzyme
      aconitase, which also functions as iron-responsive RNA-binding regulatory
      element. However, some authors have cautioned that some of such enzymes may
      merely represent "molecular fossils" of the transition from an RNA to a protein
      world and that the RNA-binding properties may not have a functional significance.
      Here I will describe enzymes that have been shown to interact with RNA (in
      several cases a newly discovered RNA-binding protein has been identified as a
      well-known metabolic enzyme) and particularly point out those whose ability to
      interact with RNA seems to have a proven physiological significance. I will also
      try to depict the molecular switch between an enzyme's metabolic and regulatory
      functions in cases where such a mechanism has been elucidated. For most of these
      enzymes relations between their enzymatic functions and RNA metabolism are
      unclear or seem not to exist. All these enzymes are ancient, as judged by their
      wide distribution, and participate in fundamental biochemical pathways.

PMID- 16410836
TI  - Molecules released by helminth parasites involved in host colonization.
AB  - Parasites are designed by evolution to invade the host and survive in its
      organism until they are ready to reproduce. Parasites release a variety of
      molecules that help them to penetrate the defensive barriers and avoid the immune
      attack of the host. In this respect, particularly interesting are enzymes and
      their inhibitors secreted by the parasites. Serine-, aspartic-, cysteine-, and
      metalloproteinases are involved in tissue invasion and extracellular protein
      digestion. Helminths secrete inhibitors of these enzymes (serpins, aspins, and
      cystatins) to inhibit proteinases, both of the host and their own. Proteinases
      and their inhibitors, as well as helminth homologues of cytokines and molecules
      containing phosphorylcholine, influence the immune response of the host biasing
      it towards the anti-inflammatory Th2 type. Nucleotide-metabolizing enzymes and
      cholinesterase are secreted by worms to reduce inflammation and expel the
      parasites from the gastrointestinal tract. An intracellular metazoan parasite,
      Trichinella spiralis, secretes, among others, protein kinases and phosphatases,
      endonucleases, and DNA-binding proteins, which are all thought to interfere with
      the host cellular signals for muscle cell differentiation. Secretion of
      antioxidant enzymes is believed to protect the parasite from reactive oxygen
      species which arise from the infection-stimulated host phagocytes. Aside from
      superoxide dismutase, catalase (rarely found in helminths), and glutathione
      peroxidase (selenium-independent, thus having a poor activity with H(2)O(2)),
      peroxiredoxins are probably the major H(2)O(2)-detoxifying enzymes in helminths.
      Secretion of antioxidant enzymes is stage-specific and there are examples of
      regulation of their expression by the concentration of reactive oxygen species
      surrounding the parasite. The majority of parasite-secreted molecules are
      commonly found in free-living organisms, thus parasites have only adapted them to
      use in their way of life.

PMID- 16410837
TI  - Dynamic force measurements of avidin-biotin and streptavdin-biotin interactions
      using AFM.
AB  - Using atomic force microscopy (AFM) we performed dynamic force measurements of
      the adhesive forces in two model systems: avidin-biotin and streptavidin-biotin.
      In our experiments we used glutaraldehyde for immobilization of (strept)avidin on
      the tip and biotin on the sample surface. Such interface layers are more rigid
      than those usually reported in the literature for AFM studies, when
      (strept)avidin is coupled with biotinylated bovine albumin and biotin with
      agarose polymers. We determined the dependence of the rupture forces of avidin
      biotin and streptavidin-biotin bonds in the range 300-9600 pN/s. The slope of a
      semilogarithmic plot of this relation changes at about 1700 pN/s. The existence
      of two different regimes indicates the presence of two activation barriers of
      these complexes during the dissociation process. The dissociation rates and
      activation energy barriers, calculated from the Bell model, for the avidin-biotin
      and streptavidin-biotin interactions are similar to each other for loading rates
      > 1700 pN/s but they are different from each other for loading rates < 1700 pN/s.
      In the latter case, the dissociation rates show a higher stability of the avidin
      biotin complex than the streptavidin-biotin complex due to a larger outer
      activation barrier of 0.8 k(B)T. The bond-rupture force is about 20 pN higher for
      the avidin-biotin pair than for the streptavidin-biotin pair for loading rates <
      1700 pN/s. These two experimental observations are in agreement with the known
      structural differences between the biotin binding pocket of avidin and of
      streptavidin.

PMID- 16410834
TI  - Transcription factor T-bet regulates inflammatory arthritis through its function
      in dendritic cells.
AB  - The transcription factor T-bet (Tbx21) plays a major role in adaptive immunity
      and is required for optimal IFN-gamma production by DCs. Here we demonstrate an
      essential function for T-bet in DCs in controlling inflammatory arthritis. We
      show that collagen antibody-induced arthritis (CAIA), a model of human RA, is a
      bipartite disease characterized by an early innate immune system component intact
      in RAG2 mice and a later adaptive immune system phase. Mice lacking T-bet had
      markedly reduced joint inflammation at both early and late time points and RAG2T
      bet double-deficient mice were essentially resistant to disease. Remarkably,
      adoptive transfer of T-bet-expressing DCs reconstituted inflammation in a T-bet
      deficient and T-bet/RAG2-deficient milieu. T-bet regulates the production of
      proinflammatory cytokine IL-1alpha and chemokines macrophage inflammatory protein
      1alpha (MIP-1alpha) and thymus- and activation-related chemokine (TARC) by DCs.
      Further, T-bet expression in DCs is required for T helper cell activation. We
      conclude that T-bet plays a vital function in DCs that links innate and adaptive
      immunity to regulate inflammatory responses. T-bet provides an attractive new
      target for the development of novel therapeutics for inflammatory arthritis.

PMID- 16410838
TI  - Indigenous peoples in the Brazilian national census.

PMID- 16410850
TI  - [Oral health of Brazilian elderly: a systematic review of epidemiologic status
      and dental care access].
AB  - Population aging and declining birth rate have significantly altered the
      Brazilian age structure pyramid. In parallel with demographic transition,
      epidemiological transition is altering morbidity-mortality profiles, without
      adequate health support for the elderly population group. By searching databases,
      the objective of this study was a systemic literature review from 1986 to 2004
      concerning the most prevalent oral problems experienced by elderly Brazilians,
      aimed at revealing the main obstacles for accessing health services. Mean DMFT
      index values in this study ranged from 25 to 31. Most articles reported a high
      percentage of edentulism. The main barriers for access to dental services were
      poor education, low income, and scarcity of public oral health services.
      Brazilian elderly oral health is thus precarious, with high edentulism rates,
      periodontal problems, decayed teeth, and great need for prostheses, reflecting
      the historical inefficacy of public dental services, limited to serial
      extractions and emergency services, based on the curative model.

PMID- 16410839
TI  - Urban violence and public health in Latin America: a sociological explanatory
      framework.
AB  - Interpersonal violence has become one of the main public health issues in Latin
      American cities. This article presents a framework for sociological
      interpretation that operates on three levels, expressed in the factors that
      originate, foment, or facilitate violence. Macro-social factors include: social
      inequality due to the increase in wealth versus poverty; the paradox of more
      schooling with fewer employment opportunities; increasing expectations and the
      impossibility of meeting them; changes in family structure; and loss of
      importance of religion in daily life. At the meso-social level the analysis
      highlights: increased density in poor areas and urban segregation; masculinity
      cult; and changes in the local drug market. The micro-social level includes: an
      increase in the number of firearms; alcohol consumption; and difficulties in
      verbal expression of feelings. The article concludes with an analysis of how
      violence is leading to the breakdown not only of urban life but also of
      citizenship as a whole in Latin America.

PMID- 16410851
TI  - Does caffeine consumption during pregnancy increase the risk of fetal mortality?
      A literature review.
AB  - The aim of this study was to evaluate the available epidemiological evidence of
      the effect of caffeine consumption during pregnancy on fetal mortality. A
      systematic qualitative review of observational studies that referred to any
      source of exposure to caffeine from food in pregnancy and to fetal mortality as
      the outcome was conducted in the databases MEDLINE and LILACS. Studies published
      between January 1966 and September 2004 were searched. The following descriptors
      were used: "caffeine", "coffee", "tea", "cola", and "cacao" to define the
      exposure and "fetal death", "stillbirth", "fetal demise", and "fetal loss" to
      define the outcome. The search strategy retrieved 32 publications, but only six
      met the inclusion criteria and three were included. One more article was found
      using "see related articles" feature in PubMed. A total of four publications were
      included in the review. The small number of publications addressing this subject,
      methodological limitations, inaccurate exposure assessment in all the studies,
      overall risks only marginally significant in most cases, and the possibility of
      publication bias preclude stating with certainty that caffeine consumption is
      actually associated with fetal death.

PMID- 16410852
TI  - [Prevalence of physical inactivity in adult women in Sao Leopoldo, Rio Grande do
      Sul, Brazil].
AB  - The aim of this study was to evaluate the prevalence of physical inactivity and
      associated factors in adult women (20-60 years) in Sao Leopoldo, Rio Grande do
      Sul, Brazil. A cross-sectional population-based study was carried out in 40
      census tracts of the city. Physical inactivity was defined as no leisure-time
      physical activity or light-intensity activities no more than once a week. Of the
      1,026 women interviewed, 380 (37.0%; 95%CI: 34.0-40.0) were classified as
      inactive. Another 609 (59.3%) reported moderate or vigorous activities less than
      three times a week. In the crude analysis, physical inactivity was higher among
      non-white women, those with higher parity, with less schooling, low income, and
      obese. After adjustment, only the effect of body mass index remained
      statistically significant. Local and national policies for counseling and
      environmental improvements are necessary to reverse the high prevalence of
      physical inactivity observed in the community.

PMID- 16410853
TI  - [Early childhood caries: prevalence and risk factors in 4-year-old preschoolers
      in Joao Pessoa, Paraiba, Brasil].
AB  - The purpose of the present study was to evaluate the prevalence of early
      childhood caries (ECC), in a cohort of children of low socioeconomic status at 48
      months of age in Joao Pessoa, Paraiba, Brazil, in relation to feeding practices,
      oral health behaviors, fluoride exposure, and enamel defects. 224 children were
      clinically examined in the Knee-Knee position at the children's home under
      natural light. Teeth were dried and cleaned with gauze, and caries (WHO index)
      and defect (DDE Index) were determined. Questionnaires on children's oral hygiene
      and dietary history were completed by parents or guardians. The SAS statistical
      program was used with the Mantel-Haenszel tests. The results showed a prevalence
      of 10.7% and 33.0% for ECC and SECC, respectively. Of all the children examined,
      79.9% had at least one tooth with enamel defects, which was the only
      statistically significant factor (p < 0.001) for ECC. The association between
      enamel defects and ECC indicates that alterations in the enamel surface may cause
      progression of dental caries.

PMID- 16410854
TI  - [Factors associated with trachoma in a low-endemic area in southeast Brazil].
AB  - A case-control study matched by age and school (n=121 pairs) was carried out
      among pre-elementary and elementary students from low-income families living in
      Greater Metropolitan Sao Paulo, Brazil, with the objective of investigating
      factors associated with trachoma in a low prevalence area. The case definition
      for trachoma was that proposed by the World Health Organization. The dependent
      variable was trachoma and the independent variables were social stratum, housing
      of migrants from endemic areas, facial hygiene habits, head of family's
      schooling, access to potable water, contact with another case in the family, and
      slum residence. Unadjusted and adjusted odds ratios (OR), with their respective
      95% confidence intervals (95%CI), were estimated by conditional logistic
      regression. In the multivariate analysis, belonging to the poorest social stratum
      (OR = 8.21; 95%CI: 1.50-44.81), housing people from endemic areas (OR = 2.44;
      95%CI: 1.10-5.46), contact with another case in the family (OR = 2.52; 95%CI:
      0.98-6.48), and facial hygiene habits (OR = 0.50; 95%CI: 0.26-0.98) were
      independently associated with trachoma.

PMID- 16410855
TI  - [Oral health of institutionalized elderly in the eastern zone of Sao Paulo,
      Brazil, 1999].
AB  - The objective was to verify oral health conditions in institutionalized elderly
      people in the city of Sao Paulo, Brazil, through epidemiological analysis. The
      sample consisted of 293 subjects and was stratified according to age (65-74 years
      and over 75) and gender. Epidemiological analysis was conducted according to WHO
      criteria to determine prevalence of oral disease. Chi-square and Mann-Whitney
      tests were used to check differences between strata. Of the subjects evaluated,
      64.8% were women and 65.2% were over 75 years old. DMFT was 30.8 with tooth loss
      of 96.3%, and this percentage was statistically greater for women (97.0%); 94.7%
      showed calculus as a major degree of periodontal condition, and only 1.8%
      presented healthy periodontal conditions and 33.3% presented loss of attachment
      ranging from 6 to 8 mm. Some 48.1% used total upper and 22.5% total lower
      prostheses. Edentulism was 68.3%. The data indicate unsatisfactory clinical
      conditions, as shown by the high CPO-D index and high percentage of edentulism.

PMID- 16410856
TI  - [Ethical conflicts in health care for adolescents].
AB  - The goal of this research was to identify ethically conflicting situations
      experienced by health professionals during health appointments with adolescents
      in order to create a protocol for action to help professionals make decisions and
      to protect the clients. The study used an observational cross-sectional method
      through interviews with health professionals at the Center for Studies on
      Adolescent Health, Rio de Janeiro State University, to obtain data from cases
      involving bioethical, ethical, and legal conflicts. Seventy-four professionals
      reported 149 cases, in which there were 250 conflicts identified through
      posterior qualitative analysis. The conflicts were interconnected, but for
      didactic reasons they were mentioned here separately. They included: secrecy and
      confidentiality, illicit activities, violence, contraception in girls less than
      15 years of age, negligence, autonomy, and recording of confidential information
      on patient medical records. We conclude that there are constant ethical conflicts
      during health appointments with adolescents, and that bioethics is a useful
      instrument for solving them. It is also essential to be familiar with the
      prevailing legislation, to consult pertinent organizations, and to evaluate
      situations individually.

PMID- 16410857
TI  - [Mental health and normality: popular conceptions in a northern coastal area of
      Bahia, Brazil].
AB  - This study focuses on signs, meanings, and practices related to mental normality
      and health in a northern coastal area of Bahia, Brazil. It discusses local
      conceptions about the non-existence or exclusive existence of mental normality,
      as well as points of view concerning total mental normality. It identifies the
      prototypes of normality, like "normal", "almost normal", and "false normal", as
      signs for distinguishing mentally normal persons. The article discusses the
      underlying values and concepts in local personal classification of mental
      normality and proposes a structural health device consisting of moral,
      scientific, religious, environmental, and social elements. It analyzes local
      normalization and mental health promotion actions and the local system of signs,
      meanings, and practices of normality. Finally, the article analyzes the primary,
      secondary, and tertiary levels of health. All these goals are met by comparing
      local conceptions with the scientific literature on medical epistemology,
      psychoanalysis, sociological labeling theory, and medical anthropology.

PMID- 16410858
TI  - [Prevalence and determinants of medicines consumption in Fortaleza, Ceara,
      Brazil].
AB  - The objective of this work was to investigate the prevalence and determinants of
      medicines consumption in Fortaleza, Ceara, Brazil. A population-based cross
      sectional study was carried out in a representative sample of 331 households. A
      total of 1,370 persons living in Fortaleza were interviewed from October 2002 to
      January 2003, and 1,366 were selected for this study. Consumers were defined as
      all persons having used one or more drugs during the preceding 15 days. The
      prevalence of medicine consumption was 49.7%. The following were the predictive
      factors for medicines consumption according to the multivariate logistic
      regression analysis: family income > 3 minimum wages, older age ( > or = 50),
      female gender, > or = 3 persons living in household, chronic disease, having a
      health insurance plan, and one or more visits to the doctor in the last three
      months. Prevalence of medication use was high in Fortaleza but was similar to
      that found elsewhere in Brazil and in other countries. Inequality in the access
      of medications was identified.

PMID- 16410859
TI  - [Knowledge about contraceptives in a population 15 years or older in a southern
      Brazilian city].
AB  - In Brazil, prevalence of contraceptive use is high, but incorrect and
      inappropriate use is frequent, suggesting limited knowledge about methods. This
      study thus evaluated the knowledge about the most widely used contraceptive
      methods, measured through a score (0-10) and related factors. A population-based
      cross-sectional study was performed, with 3,542 subjects ages 15 or older,
      residing in the urban area of Pelotas, Rio Grande do Sul State. The mean overall
      knowledge score was 4.65 (sd = 2.07): 5.02 (sd = 2.10) for women and 4.18 (sd =
      1.92) for men. Lower age, higher schooling, a report of unwanted pregnancy, and
      any lifetime use of contraceptive methods (exclusive or combined) were associated
      with higher knowledge scores among men, while for women, the determinants of
      higher knowledge were higher age, living with a partner, higher schooling, higher
      socioeconomic status, not reporting a religion, and any lifetime use of
      contraceptive methods (exclusive or combined). Despite high prevalence of any
      lifetime contraceptive use (75.3%), knowledge is still limited about the most
      widely used methods, as well as about the menstrual cycle and fertile period.

PMID- 16410860
TI  - Sandfly fauna in a military training area endemic for American tegumentary
      leishmaniasis in the Atlantic Rain Forest region of Pernambuco, Brazil.
AB  - The aim of this study was to characterize the sandfly fauna in a military
      training area situated in the "Zona da Mata" region of Pernambuco State, Brazil,
      where human cases of American tegumentary leishmaniasis (ATL) had been observed,
      caused by Leishmania (Viannia) braziliensis. The occurrence of 16 sandfly species
      in the Marshall Newton Cavalcanti Military Training Camp (CIMNC) indicates an
      important diversity of sandfly species in this study area. Lutzomyia complexa was
      the most common species (51.36%) followed by L. choti (43.54%). All the captures
      were made in areas where training activities were conducted and where clinical
      cases had been detected in individuals performing training, following this
      period. The data relating the sandfly behavior to previous data in the same area
      provides strong evidence for the occurrence of an enzootic cycle of the parasite,
      and outbreaks followed the period of training activities in the remaining
      Atlantic Rain Forest and secondary forest areas.

PMID- 16410861
TI  - Changes in family structure and regret following tubal sterilization.
AB  - Tubal sterilization is one of the contraceptive methods whose use has increased
      the most in Brazil, but a growing number of women have expressed regret after the
      procedure. A case-control study was conducted at the Centro Integrado de Saude
      Amaury de Medeiros (CISAM), Recife, Pernambuco, Brazil, in 1997 to investigate
      the association between changes in family structure and request for or submittal
      to surgical reversal of tubal sterilization, comparing 304 sterilized women who
      had requested or submitted to reversal of tubal sterilization and 304 women who
      were also sterilized but had not requested, had not submitted to, and who did not
      wish to submit to reversal. The simple and adjusted odds ratios were estimated
      using logistic regression. The results of the current study showed that death of
      children, partners without children prior to the current union, and partner
      change after tubal sterilization were associated with the request for or
      submittal to reversal of tubal sterilization. More strict criteria are suggested
      in the indication of tubal sterilization, including an in-depth profile of the
      woman requesting tubal sterilization and identification of risk factors for
      future regret.

PMID- 16410862
TI  - [High prevalence of Cyclospora cayetanensis among indigenous people in Bolivar
      State, Venezuela].
AB  - The intestinal coccidioses caused by Cryptosporidium parvum, Isospora belli, and
      Cyclospora cayetanensis are parasitoses of major medical importance, but many
      epidemiological aspects of these infections are still unknown in Bolivar State,
      Venezuela. To determine the prevalence of intestinal parasites and especially of
      intestinal coccidiosis, an indigenous population in San Antonio de Morichal was
      evaluated from July 2003 to April 2004. Stool samples obtained by spontaneous
      evacuation were preserved in potassium dichromate 2.5% and examined by the
      formalin-ether concentration method and Kinyoun staining. Of the 160 indigenous
      people examined, 92.5% (148 cases) were infected. Entamoeba coli (58.8%), Ascaris
      lumbricoides (38.8%), and Giardia lamblia (18.8%) were the most prevalent
      intestinal parasites. Coccidiosis prevalence was 13.1%, and cyclosporiasis was
      the most prevalent with 11.9% (19 cases). One subject with C. parvum oocysts and
      another with I. belli oocysts were diagnosed. There was no difference according
      to sex (p > 0.05) and age (chi2 = 5.6; f.g. = 6) among individuals infected with
      C. cayetanensis. Of these, two cases had only diarrhea. In conclusion, a high
      prevalence of intestinal coccidiosis infection was found among indigenous people
      from this community, with C. cayetanensis as the most prevalent infection.

PMID- 16410863
TI  - [Characteristics of candidates for surgical sterilization and factors associated
      with type of procedure].
AB  - In 1999 the Municipal Health Department in Ribeirao Preto, Sao Paulo, Brazil,
      implemented the provision of surgical contraceptive methods according to
      prevailing legal requirements. This study aimed to characterize the candidates
      for surgical sterilization and study the variables associated with the type of
      procedure. A total of 95 candidate patient records were studied, and statistical
      logistic regression analysis and Fisher's exact test were performed considering a
      significance level of ? = 0.05. Most candidates had stable partners, low
      schooling, and low income, were satisfied with their number of children, and had
      already tried to limit the number of children using reversible contraceptives.
      Mean age was 34.2 years, 45.3% underwent female sterilization, 35.8% underwent
      vasectomy, and 18.9% did not submit to any procedure. The odds of a man older
      than 35 having a vasectomy were 6.1 times that of a younger man (OR = 6.1; 95%CI:
      2.4-16.4). More married men submitted to vasectomy than men who cohabited (OR =
      4.0; 95%CI: 1.5-12.4). Women with four or more children were more likely to
      undergo sterilization than those with fewer children (OR = 3.1; 95%CI: 1.1-8.5).

PMID- 16410864
TI  - [Obesity and poverty: the apparent paradox. A study among women from the Rocinha
      slum, Rio de Janeiro, Brazil].
AB  - In recent decades the Brazilian population has undergone intense changes in its
      nutritional conditions, especially with an increase in obesity. According to the
      National Survey on Health and Nutrition in 1989, 32.0% of adults were overweight.
      However, distribution of the problem is not homogeneous. The highest prevalence
      occurs among poor women in the Southeast. Understanding this apparent paradox
      requires the search for approaches capable of overcoming simplistic
      interpretations about eating practices. Thus, the objective of this study was to
      understand obesity combined with poverty, focusing beyond economic determinants
      on constraints of a cultural and symbolic nature. From this perspective, the
      study analyzed the daily lives of poor women who used a Municipal Health Center
      and resided in the Rocinha slum in Rio de Janeiro. The results showed the
      complexity of the relationship between obesity and poverty. Cultural and material
      life aspects as well as different concepts of eating and the body proved to be
      fundamental elements for the analysis of the multiple facets of obesity in
      Brazil.

PMID- 16410865
TI  - [Prevalence of infection by Leishmania chagasi using ELISA (rK39 and CRUDE) and
      the Montenegro skin test in an endemic leishmaniasis area of Maranhao, Brazil].
AB  - A prospective study was undertaken in 1,520 children less than 15 years of age in
      Sao Jose de Ribamar, Maranhao, Brazil, from June 1994 to January 1995, to
      evaluate the prevalence and characteristics (socioeconomic, environmental, and
      behavioral) associated with infection by Leishmania chagasi. Montenegro skin test
      (MST) and enzyme-linked immunosorbent assay (ELISA-rK39 and CRUDE) test were used
      to detect infection. The statistical analysis used the chi2 test with Yates
      correction and a p value less than 0.05 was considered statistically significant.
      Prevalence of infection was 61.7% as measured by MST, 19.4% according to ELISA
      (rK39), and 19.7% by ELISA (CRUDE). Association was detected between
      leishmaniasis in the family, water supply, application of insecticide, and
      infection by L. chagasi using MST. No association with infection by L. chagasi
      was detected using ELISA rK39 or CRUDE. More effective control measures are
      needed to reduce prevalence and to detect asymptomatic cases in this high
      percentage of infected children.

PMID- 16410866
TI  - Generic drugs in Brazil: known by many, used by few.
AB  - This study evaluated knowledge and use of generic drugs in a population-based
      sample of adults from a southern Brazilian city. The outcomes were: the
      proportion of generics in total medicines used; theoretical and practical
      knowledge about generics; and strategies used to buy medicines on medical
      prescriptions. The recall period for drug utilization was 15 days. The proportion
      of generics in total medicines was 3.9%. While 86.0% knew that generics cost less
      and 70.0% that the quality is similar to brand name medicines, only 57.0% knew
      any packaging characteristics that distinguish generics from other medicines. The
      highest proportion of generic drug utilization was in the antimicrobial
      pharmacological group. A brand name medicine (with a brand similar to the generic
      name) was mistakenly classified as a generic through photos by 48.0% of the
      interviewees. Among subjects who bought medicines in the 15-day period, 18.9%
      reported buying a generic, but this result should be interpreted with caution,
      because the population frequently fails to differentiate between generics and
      other medicines.

PMID- 16410867
TI  - Studies on the feeding habits of Lutzomyia (N.) intermedia (Diptera,
      Psychodidae), vector of cutaneous leishmaniasis in Brazil.
AB  - The precipitin test was applied to identify the blood meal sources of Lutzomyia
      intermedia, collected in two distinct habitats: inside houses and in the
      peridomicile, in Mesquita, Rio de Janeiro State, Brazil, a transmission area of
      Leishmania (V.) braziliensis. The following antisera were tested: human, avian,
      equine, rodent, and opossum. From a total of 370 females analyzed, 128 specimens
      from the domicile and 59 from the peridomicile reacted with specific antisera.
      The anthropophily of L. intermedia was confirmed in both habitats; likewise, the
      feeding of this sand fly species on domestic animals, observed in previous
      entomological surveys, was confirmed by the strong reactivity with avian, canine,
      and equine antisera. However, feeding on rodents, mammals frequently found inside
      and around houses, represents further evidence related to the vector competence
      of L. intermedia, since synanthropic and sylvatic rodents have been considered a
      putative reservoir of L. (V.) braziliensis.

PMID- 16410869
TI  - [Clinical and demographic data concordance comparing authorizations for high
      complexity oncological procedures and patient records of women treated under the
      Unified National Health System in Rio de Janeiro, Brazil].
AB  - This study investigates the concordance of clinical and demographic data under
      the Unified National Health System (SUS) in Brazil, comparing authorizations for
      high-complexity oncological procedures in breast cancer with a random sample of
      310 corresponding medical records in Rio de Janeiro State, Brazil. Concordance
      was verified using kappa (K), prevalence-adjusted bias-adjusted kappa (PABAK),
      weighted-kappa (KW), intra-class correlation (ICC), and relative frequency
      statistics. 95% confidence intervals were estimated, and Landis and Koch criteria
      were applied for concordance interpretation. Assuming PABAK as the most
      appropriate statistic for the variables analyzed, we observed a moderate
      concordance for cancer staging, PABAK = 0.63 (95%CI: 0.56-0.70), and for
      morphological diagnosis, PABAK = 0.84 (95%CI: 0.72-0.96). For date of birth and
      date of diagnosis, ICCs were 0.96 (95%CI: 0.95-0.96) and 0.92 (95%CI: 0.90-0.94),
      respectively. Concordance regarding municipality of residence was 52.9%. The
      study indicates that, except for municipality of residence, the data concordance
      comparing authorizations for procedures and patient medical records in Rio de
      Janeiro allows its application to epidemiological and health services research,
      as well as for health planning purposes.

PMID- 16410868
TI  - [Critical evaluation of the Primary Care Information System (SIAB) and its
      implementation in Ribeirao Preto, Sao Paulo, Brazil].
AB  - As the health information system used by the Family Health Program teams, the
      Primary Care Information System (SIAB) is a potential tool for follow-up of
      registered families and local planning, thus motivating the present study. Semi
      structured interviews were held with key individuals in this health information
      system chain, among Family Health Teams in the municipality of Ribeirao Preto and
      surrounding region, Sao Paulo State, Brazil, with the objective of analyzing
      certain characteristics in the system, including: knowledge and having received
      training to handle it and utilization for local planning and social control. The
      study concluded that the SIAB is an easy system to handle, but that it presents
      some limitations already found in other health information systems, such as:
      difficulty in identifying individuals in the program, limited number of diseases
      reported, and limited utilization to back planning and decision-making at the
      local level. Therefore, the analysis of the SIAB was highly important for
      improving this health information system and can contribute to future
      improvements and adaptations in the program.

PMID- 16410870
TI  - [Risk perception related to work in a rural community of Rio de Janeiro State,
      Brazil: pesticides, health, and environment].
AB  - The present study applies the risk perception analytical methodology based on
      rapid surveys. It took place in the micro-basin of the Sao Lourenco Creek in Nova
      Friburgo, Rio de Janeiro State, Brazil. The methodological approach was based on
      participatory observation, semi-structured interviews with 24 key informants
      selected among local farmers (N = 120), and evaluation of local work processes.
      Field data analysis revealed some issues related to the risk perception profile
      in the study population, including the development of defensive strategies to
      deal with work hazards, the importance of communication in developing workers'
      risk perceptions, the subjective responses to potentially hazardous situations,
      and the role of individual risk perception as a determinant of human exposure to
      pesticides. The results evoked the importance of systematically incorporating
      risk perception analyses into intervention strategies, especially in educational
      risk communication campaigns.

PMID- 16410871
TI  - [Child health in poor areas of North and Northeast Brazil: a comparison of areas
      covered by the Children's Mission and control areas].
AB  - Community surveys are essential to estimate health indicators, evaluate health
      programs, and define health interventions. In 2002, a cross-sectional survey of
      children under five was conducted in 18 areas of the poorest counties in North
      and Northeast Brazil. Nine areas were visited by volunteer community health
      workers (CHW) under the Children's Mission, and the others were not visited.
      Using a standard questionnaire, trained interviewers collected information at the
      household level for 1,528 children, 782 of whom were visited monthly by CHWs and
      772 were not. All the children and their families were living below the poverty
      line; 40.0% of the parents were illiterate, per capita daily income was about
      US$0.30, and household conditions were substandard. However, most were living
      less than 1km from a public health service and almost all children who were
      referred to these services received medical care. Prenatal care was also poor in
      terms of number of medical visits and laboratory tests. Children visited by CHWs
      from the Children's Mission received better care in terms of growth monitoring,
      number of medical check-ups, and prenatal iron supplementation.

PMID- 16410872
TI  - Paracoccidioidomycosis mortality in the State of Parana, Brazil, 1980/1998.
AB  - The paracoccidioidomycosis mortality rate in the State of Parana, Brazil
      (1980/1998) was analyzed using the death registry data from the Brazilian
      Mortality Information System and the estimated population from the Brazilian
      Institute of Geography and Statistics. To qualify the deaths, we deployed ICD-9
      for 1980/1995 and ICD-10 for the more recent years. During this period there were
      551 deaths from paracoccidioidomycosis in the State of Parana. Most of the deaths
      were in male in the 30-59-year age group. The average annual mortality rate was
      3.48 per million inhabitants, showing a tendency to stabilize during the study
      period. Paracoccidioidomycosis was the fifth cause of mortality among the
      predominantly chronic infectious diseases and had the highest mortality rate
      among the systemic mycoses. Paracoccidioidomycosis was observed in 184 counties
      in the State of Parana. Most deaths were recorded in the North-Central meso
      region, and the highest mortality rate occurred in the West meso-region.

PMID- 16410873
TI  - [Paternal involvement in the care of small children: an ethnographic study of low
      income families].
AB  - The present study focused on father's involvement in the health care of small
      children (under six years) in low-income families. An ethnographic study was
      performed with interviews and participatory observation. We visited families in
      an outlying low-income urban neighborhood in Northeast Brazil, for nine months.
      Children appeared as a fundamental dimension in the lives of men and women,
      constituting a common reason for forming a family nucleus. The paternal role
      involved three key dimensions: education, in which the father was essential; body
      care, usually considered a female attribution; and preservation of integrity,
      considered an obligation for all family members. Despite the fact that
      traditional identification of gender roles still persists, based on contrasting
      discourses and practices, in all families (and especially in nuclear ones) there
      were dimensions in which men participated actively, demonstrating physical and
      emotional proximity with their children.

PMID- 16410874
TI  - [Phenomenology of viscerality: the impact of medical imaging technologies on
      corporeality].
AB  - This article deals with the phenomenological dimension of the inner body in light
      of the success of new medical imaging technologies outside the biomedical field
      itself. The new technologies contribute not only to the disembodiment of
      subjectivity, but also to the virtualization and objectification of corporeality.
      They neglect the constitutive subjective dimension of the living body. The
      article investigates this fundamental dimension of corporeality, ungraspable
      through medical imaging.

PMID- 16410875
TI  - Caffeine as an environmental indicator for assessing urban aquatic ecosystems.
AB  - This study aimed to evaluate the co-occurrence of caffeine and the extent of its
      influence as compared to other traditional water quality parameters
      (microbiological and physico-chemical) in order to characterize it as an
      efficient indicator of anthropic pollution of urban aquatic environments.
      Caffeine is an ingredient in a variety of beverages (coffee, tea, and caffeinated
      soft drinks) and numerous food products (chocolate, pastries, and dairy
      desserts). Although the human body metabolizes this stimulant efficiently,
      between 0.5 and 10.0% is excreted, mostly in the urine. Analysis of water samples
      from the Leopoldina Basin and Guanabara Bay revealed a significant difference
      between areas not commonly affected by nutrient enrichment or sewage inputs and
      areas chronically influenced by sewage discharges and elevated eutrophication.
      Monitoring caffeine will be fundamental in stressed urban aquatic environments
      where frequent accidental ruptures of sewer lines and discharges of untreated
      effluents impede effective water quality evaluation with traditional indicators.

PMID- 16410876
TI  - [Ecoefficiency: a tool to reduce solid waste production and waste of materials in
      health care units].
AB  - The main goal of health care units is patient care. During this process, water,
      energy, and different materials are used, generating liquid effluents and solid
      waste that require adequate treatment. Although medical waste management demands
      increasing attention by health care units, reduction in the generation of medical
      solid waste has still not been set as a priority. Using ecoefficiency techniques,
      it is possible to demonstrate whether a company is meeting it standards for
      quality, procedures, environmental control, and economic efficiency. Therefore,
      ecoefficient companies realize both economic and environmental benefits through
      progressive reduction in solid waste, liquid effluents, and air emissions. This
      new concept requires further dissemination among health care units, since many
      are making efforts to improve quality of services, but still overlook the issue
      of waste and generate an increasing amount of solid waste. This leads not only to
      waste of raw materials but also additional costs for proper waste management.

PMID- 16410877
TI  - [Breastfeeding promotion, protection, and support in primary health care in the
      State of Rio de Janeiro, Brazil: a case of evidence-based public health policy].
AB  - This article evaluates a policy for breastfeeding promotion, protection, and
      support in primary health care units in Rio de Janeiro State, Brazil, analyzing
      the assumptions, interventions, and results based on a log-frame model. A
      systematic review sought to identify effective procedures and strategies for
      extending breastfeeding duration, constituting the basis for creating "Ten Steps"
      in the "Breastfeeding-Friendly Primary Care Initiative" launched in Rio de
      Janeiro State in 1999. A corresponding evaluation method was developed and
      applied to verify the performance of 24 primary health care units from different
      parts of the State. A direct association was found between the practical
      implementation of these steps and prevalence of exclusive breastfeeding, as well
      as with mothers' satisfaction. An analysis of meanings ascribed by pregnant women
      and mothers to the support provided for breastfeeding identified five categories:
      "no support", "doubtful support", "encouragement", "guidance", and "partnership".
      The evaluation model allowed staff at the health care units to recognize
      opportunities for improving the program, in order to reverse the current low
      prevalence of exclusive breastfeeding.

PMID- 16410878
TI  - [Prevalence and factors associated with iron deficiency in infants treated at a
      primary care center in Belem, Para, Brazil].
AB  - The objective was to verify the occurrence of iron deficiency and associated
      factors in infants. This cross-sectional study included 365 infants (defined here
      as 6-24 months of age) treated at a primary care center in Belem, Para, Brazil.
      Iron-deficiency anemia (hemoglobin < 11 g/dl and ferritin < 12 microg/l) was
      diagnosed in 55.1% of the sample, depletion of body iron reserves (hemoglobin <
      11 g/dl and ferritin < 12 microg/l) in 15.3%, and iron sufficiency (hemoglobin <
      11 g/dl and ferritin < 12 microg/l) in 18.1%. The results of the logistic
      regression model showed associations between iron deficiency (ferritin < 12
      microg/l) and: 6-12 month age group, OR (odds ratio) = 3.67 and 95% CI: 1.93
      7.04; non-utilization of iron-fortified formula as the first milk used after
      interrupting breastfeeding, OR = 1.93 and 95%CI: 1.04-3.60; and per capita income
      < or = 1 minimum wage, OR = 2.69 and 95%CI: 1.30-5.59. The occurrence of iron
      deficiency was high, showing the need to adopt effective measures to prevent this
      important public health problem.

PMID- 16410880
TI  - Anthropometry of elderly residents in the city of Sao Paulo, Brazil.
AB  - The article presents gender and age-specific selected anthropometric data for a
      representative sample of elderly Brazilians in the city of Sao Paulo. This was a
      cross-sectional, population-based household survey. A total of 1,894 older adults
      (men and women, > 60 years) were examined from January to March 2001. Data were
      presented as means and percentiles for body mass (BM); height or stature (ST);
      body mass index (BMI); waist (WC), hip (HC), arm (AC), and calf (CC)
      circumferences; triceps skinfold thickness (TST); and arm muscle circumference
      (AMC), and differences were described according to age (all variables) and gender
      (BMI). Except for HC (men), all anthropometric variables were lower in the oldest
      than in the youngest individuals (p < 0.01) in both genders. BMI was
      significantly higher (p < 0.01) in women than men (all age groups). The
      observations suggest that there is loss of muscle mass and redistribution and
      reduction of fat mass with age (both genders). The data can be used in clinical
      practice and epidemiological studies based on interpretation of anthropometric
      measurements in the elderly in Sao Paulo.

PMID- 16410879
TI  - [Caffeine intake and food sources of caffeine and prematurity: a case-control
      study].
AB  - Caffeine (1,3,7-trimethylxanthine) is an alkali that easily crosses the placental
      barrier and can interfere in the growth and development of fetal cells and
      compromise fetal oxygenation. Considering the widespread consumption of foods
      containing caffeine in Brazil, the aim of this study was to evaluate the
      association between total caffeine consumption (including its food sources) and
      prematurity. A case-control study of 140 cases (newborns with gestational age
      less than 37 weeks) and 162 controls (newborns with 37 weeks gestational age or
      greater) evaluated caffeine consumption during pregnancy. Intake measurement used
      a semi-quantitative food frequency questionnaire based on the following foods:
      coffee, tea, and powdered chocolate. Total caffeine consumption (including food
      sources) during pregnancy was not associated with prematurity, and most intakes
      were less than 300 mg/ day. Caffeine consumption in the present study does not
      support guidelines against caffeine consumption by Brazilian pregnant women.

PMID- 16410881
TI  - [Human rabies prophylaxis in Campo Grande, Mato Grosso do Sul State, Brazil,
      2002].
AB  - Timely application of adequate treatment, speedy and thorough observation of
      animals, and streamlined information transfer provide quality rabies
      epidemiological surveillance in cases of attacks by animals. This study aims to
      evaluate rabies surveillance and the use of a computerized system in the
      surveillance process. A total of 4,168 attacks by animals were analyzed. The
      injuries were considered severe in 65.9% of cases. Dogs accounted for 87.6% of
      the severe cases, cats 10.5%, and bats 0.6%. Two treatment recording sites were
      analyzed. According to the rabies treatment record sheet, 41.9% of the treatments
      were adequate; in cases with negative observation, 7.4% showed adequate
      treatment. According to the vaccination program, 42.2% of the prescribed
      treatments were correct; in cases with negative observation, 3.2% received
      adequate treatment. The study concluded that there should be improved prescribing
      and recording of treatment, as well as a search for missing cases, in order to
      improve the quality of the services and avoid more severe outcomes from animal
      attacks.

PMID- 16410882
TI  - Human T-cell lymphotropic virus type II in Guarani Indians, Southern Brazil.
AB  - Human T-cell lymphotropic virus type II (HTLV-II) is found in many New World
      Indian groups on the American continent. In Brazil, HTLV-II has been found among
      urban residents and Indians in the Amazon region, in the North. Guarani Indians
      in the South of Brazil were studied for HTLV-I/II infection. Among 52
      individuals, three (5.76%) showed positive anti-HTLV-II antibodies (enzyme-linked
      immunosorbent assay and Western blot). This preliminary report is the first
      seroepidemiological study showing HTLV-II infection among Indians in the South of
      Brazil.

PMID- 16410883
TI  - [Occurrence of Leptospira spp. soropositive stray dogs in Itapema, Santa
      Catarina, Brazil].
AB  - This study aimed to verify Leptospira spp. serovar infections in stray dogs in
      Itapema, Santa Catarina, Brazil. Serum samples were collected from 590 stray dogs
      and tested against 25 Leptospira spp. serovars using the microscopic
      agglutination test. Prevalence of anti-leptospiral antibodies against one or more
      serovars was 10.5%. The most frequent serovar was pyrogenes, positive in 26
      (18.0%) samples, followed by canicola with 20 (13.8%) and icterohaemorragiae and
      copenhageni with 18 (12.5%, with antibody titers from 1:100 to 1:3,200).
      Significant prevalence (10.4 to 11.1%) was also detected against serovars
      castellonis, butembo, and grippothyphosa.

PMID- 16410884
TI  - [Canine American cutaneous leishmaniasis in municipalities of northern Parana
      State, Brazil].
AB  - American cutaneous leishmaniasis (ACL) is an endemic disease in northern Parana
      State, where it affects humans and dogs. This study aimed to verify the
      occurrence of the canine disease in ACL endemic areas. From September 1999 to
      July 2002, dogs were investigated in 7 rural areas of 5 municipalities where
      autochthonous human cases of ACL had been reported. Parasitological and
      serological methods were used. Fourteen of 67 dogs studied (20.9%) had lesions
      suggestive of ACL, of which 3 (21.4%) were infected with Leishmania sp. Indirect
      immunofluorescence for Leishmania (Viannia) braziliensis was positive in 37
      (55.2%) of 67 dogs. The results showed that human and canine ACL occur
      simultaneously and indicate the need for additional studies to elucidate the role
      of dogs in the ACL transmission cycle in the area studied.

PMID- 16410885
TI  - In vitro activity of tigecycline, a new glycylcycline, tested against 1,326
      clinical bacterial strains isolated from Latin America.
AB  - The in vitro activity of tigecycline (former GAR-936), a new semisynthetic
      tetracycline, was evaluated in comparison with tetracycline and other
      antimicrobial agents. MATERIAL AND METHODS: A total of 1,326 contemporary
      clinical isolates collected from the Latin American region were collected in 2000
      2002 period and tested with microdilution broth according to the CLSI guidelines.
      The bacterial pathogens evaluated included Staphylococcus aureus (505),
      Streptococcus pneumoniae (269), coagulase-negative staphylococci (CoNS; 227),
      Haemophilus influenzae (129), Enterococcus spp. (80), Moraxella catarrhalis (54),
      beta-haemolytic streptococci (28), viridans group streptococci (26), and
      Neisseria meningitidis (8) RESULTS: Tigecycline demonstrated excellent activity
      against all Gram-positive cocci, with 90% of penicillin-resistant S. pneumoniae
      strains being inhibited at 0.12 microg/mL, while the same isolates had an MIC90
      of > 16 microg/mL for tetracycline. All Enterococcus spp. were inhibited at 0.25
      microg/mL of tigecycline. Tigecycline (MIC50, 0.25 microg/mL) was eight-fold more
      potent than minocycline (MIC50, 2 microg/mL) against oxacillin-resistant S.
      aureus (ORSA); all ORSA were inhibited at < 2 microg/mL of tigecycline.
      Tigecycline demonstrated excellent activity (MIC50, 0.5 microg/mL) against CoNS
      with reduced susceptibility to teicoplanin (MIC, 16 microg/mL). Tigecycline also
      showed high potency against respiratory pathogens such as M. catarrhalis (MIC50,
      0.12 microg/mL) and H. influenzae (MIC50, 0.5 microg/mL). No tigecycline
      resistant isolates were detected when the proposed susceptible breakpoints (< 4
      microg/mL) was applied. CONCLUSIONS: This results indicate that tigecycline has
      potent in vitro activity against clinically important pathogenic bacteria,
      including Gram-positive isolates resistant to both tetracycline and minocycline.

PMID- 16410886
TI  - Evaluation of the secretory immunoglobulin A levels in the colostrum and milk of
      mothers of term and pre-term newborns.
AB  - OBJECTIVE: To determine and to compare the levels of secretory immunoglobulin A
      in samples of colostrum and milk of mothers of term and preterm neonates.
      MATERIAL AND METHODS: The levels of secretory immunoglobulin A of 10 mothers of
      term neonates and 10 mothers of preterm neonates were determined from 5 mL of
      colostrum or milk collected on the 1st, 4th, 10th and 15th days of the puerperal
      period, using the radial immunodiffusion technique. We employed anamnesis, as
      well as physical and gynecological exams in women in the puerperal period. All
      the patients were attended at the Januario Cicco Maternity College. RESULTS: The
      secretory immunoglobulin A levels were significantly higher in the colostrum and
      milk of mothers of preterm neonates when compared with the levels found in
      colostrum and milk of mothers of term neonates (Mann-Whitney test, p<0.0001).
      There was a significant decline in the secretory immunoglobulin A levels of the
      colostrum and milk of the mothers of term and preterm neonates during the four
      periods (Kruskal-Wallis test, p<00001). CONCLUSIONS: The secretory immunoglobulin
      A levels in colostrum and milk of mothers of preterm neonates were significantly
      higher than in the mothers of term neonates, demonstrating immunological
      adaptation in preterm neonate breast-feeding.

PMID- 16410887
TI  - Immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus
      influenzae type B conjugate vaccine (PRP-T) for primary and booster vaccinations.
AB  - OBJECTIVE: To evaluate the immunogenicity of a combined DTPa-HB vaccine co
      administered with Haemophilus influenzae type b conjugate vaccine (PRP-T) in
      Brazilian infants. MATERIAL AND METHODS: A prospective and open clinical study,
      in which 110 infants were immunized with a three-dose primary vaccination regime
      at two, four and six months of age and with a single booster vaccination. Blood
      samples were drawn immediately before the first dose, one month after the third
      dose, at the time of the booster dose and one month after the booster to assess
      seropositivity and antibody geometric mean titers (GMTs) of antibodies for
      diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and for the three
      pertussis antigens: Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and
      Pertactin (PRN). RESULTS: Among the original 110 infants, 93 completed the study.
      Seropositivity was 100% for all seven involved antibodies, after the primary
      vaccination course. At the time of the booster dose, all antibodies (except
      diphtheria 33.7% and anti-PT 59%) were seropositive for more than 94% of
      subjects. After the booster, seropositivity increased to 100% for all antibodies.
      The GMT of these antibodies followed a similar pattern, with a strong increase
      after the primary course, followed by a second increase after the booster dose.
      At this time, GMT was 2- to 7-fold higher than after the primary course, for all
      vaccine components. CONCLUSIONS: Concomitant administration of DTPa-HB and Hib
      vaccines elicited strong seroprotection for all the antigenic components. No
      interference with antibody response was evident. The vaccines provided high
      immunogenicity, following both the primary vaccinations and the booster dose.

PMID- 16410888
TI  - Seroprevalence of hepatitis B and C in Brazilian army conscripts in 2002: a cross
      sectional study.
AB  - Hepatitis B and C constitute important public health problems worldwide. In
      Brazil, studies on prevalence of viral hepatitis have local and regional
      characteristics; consequently it is difficult to define the national
      epidemiological situation. Our objective was to evaluate the seroprevalence of
      hepatitis B and C in conscripts of the Brazilian Army. A transversal study among
      males aged 17 to 22 years was conducted nationwide. After informed consent, each
      volunteer filled in a social-behavioral questionnaire and had blood drawn to test
      for HBsAg and anti-HCV. A total of 7,372 volunteers were evaluated in the second
      half of 2002. The prevalence of HBsAg was 2.6% (95% confidence interval: 2.2,
      3.0) and that of anti-HCV was 1.5% (95% confidence interval: 1.2, 1.8). A wide
      variation among macro regions and states in the same region was observed for both
      markers. In conclusion, although this population theoretically had a low risk for
      HBV and HCV infection, these results are higher than expected for this age range.
      These findings may indicate a change in the pattern of HBV and HCV transmission
      in Brazil. Due to the different dynamics of these epidemics, further studies are
      warranted to confirm these apparent trends.

PMID- 16410889
TI  - Hepatitis B in healthcare workers: prevalence, vaccination and relation to
      occupational factors.
AB  - The prevalence of hepatitis B virus (HBV) in healthcare workers (HCW) in
      Brazilian university hospitals is high. However, vaccination of these workers and
      relations with occupational factors are not well documented. A prospective study
      was made of 1,433 HCW and 872 administrative employees of the Hospital de Base
      (HB), Sao Jose do Rio Preto, SP, Brazil, and 2,583 blood donor candidates from
      the Hospital Blood Bank. HCW were observed from January 1994 to December 1999.
      Data were obtained from exams made when a worker entered hospital service,
      periodically and after work-related injuries. Serological reactions were analyzed
      in HCW who received HBV vaccine. Occupational and non-occupational information
      was obtained through a questionnaire. The prevalence of HBV among HCW (0.8%) was
      significantly higher than in blood-donor candidates (0.2%). Among the HCW who
      were vaccinated, 86.4% were immunized. Multivariate analysis revealed that
      increased age reduced the chance of immunization. Among the occupational factors,
      time in service contributed to a 14% increase in the chances of having positive
      serology, and work-related injuries increased the risk of HBV infection 4.29
      times. The maximum risk sector presented a larger number of HCW with positive
      anti-HBc serology. There was a higher seroconversion in HCW who received the full
      set of HBV vaccines. In HCW with positive serology, the factors that presented
      greatest risks were time in service, work-related injuries and maximum risk
      sector.

PMID- 16410890
TI  - Susceptibility of Streptococcus pneumoniae to penicillin in the state of Minas
      Gerais, Brazil from 1997-2004.
AB  - We monitored the susceptibility to penicillin of invasive strains of
      Streptococcus pneumoniae in two reference laboratories; 502 positive cultures
      from patients with an active invasive infectious process were analyzed.
      Streptococcus pneumoniae was identified through conventional procedures, and the
      oxacillin disc diffusion method was used to check for penicillin susceptibility.
      Statistical analysis included calculations of the frequency distribution, with
      95% confidence intervals (CI), as well as chi-square tests and chi-square for
      linear trend for temporal analysis of susceptibility. The bacterium was isolated
      from patients less than a year old (40.7% of the isolates), from infants (55.9%),
      and from individuals less than 15 years old (64.4%). The majority (88.2%, 95% CI
      = 85.5%-91.1%) of the 502 isolates were susceptible to penicillin. There was no
      significant temporal trend of elevation of resistance rate during the study
      period (p=0.56). We conclude that resistance of S. pneumoniae to penicillin is
      not yet an important clinical-epidemiological concern in the State of Minas
      Gerais. To provide necessary support for the adoption of therapeutic and
      prophylactic measures, epidemiological surveillance should be implemented at a
      national level to monitor the profile of susceptibility/resistance of S.
      pneumoniae to penicillin and other antimicrobials.

PMID- 16410891
TI  - Human papillomavirus infection in Rio de Janeiro, Brazil: a retrospective study.
AB  - There is considerable data to support a central role for human papillomavirus
      (HPV) in the etiology of cervical cancer. More than a 100 HPV types have been
      described, and 40 have been isolated from benign and malignant genital lesions.
      Consequently, there is strong motivation to evaluate HPV testing for cervical
      cancer screening. Few studies concerning the natural history of HPV infection
      have been conducted in the state of Rio de Janeiro. We determined the prevalence
      of HPV types in female genital lesions by using Hybrid Capture Assay (HCA) and we
      retrospectively analyzed the course of HPV infection. Our sample included 788
      women attended at Laboratorios Sergio Franco. The average age of the participants
      was 29.6 years. HPV prevalence and cytological diagnosis were determined. The
      overall prevalence of HPV DNA in the study group was 50.1% (395/788), ranging
      from 25% (NORMAL) to 100% in high-grade intraepithelial lesions (HSIL). High risk
      HPV was found in 12% inflammatory, 58.3% HPV, 63.2% LSIL and 100% HSIL. A
      retrospective analysis of 78 patients showed that 22 presented persistent
      lesions, 2 had progressive lesions, 4 had regressive lesions, 13 showed latent
      infections, 18 were transiently infected and 19 were submitted to curative
      treatment. No cases of cancer were registered in this population, which can
      afford private medical care and regular follow-up exams. We suggest that HCA be
      used in specific cases involving persistent and recurrent lesions.

PMID- 16410892
TI  - Helicobacter pylori infection in adults from a poor urban community in
      northeastern Brazil: demographic, lifestyle and environmental factors.
AB  - We investigated the prevalence and the risk factors for infection with
      Helicobacter pylori in a randomly-selected population of adults from a low-income
      community in Northeastern Brazil. Helicobacter pylori infection was determined by
      ELISA. Risk factors were assessed using a structured interview. Two hundred and
      four individuals were included in the study, including 49 males and 155 females,
      ranging from 18 to 80 years old. Overall, 165 of 204 participants (80%) were H.
      pylori positive, without significant gender differences (p= 0.49). The infection
      rate was of 84.7% in subjects 18 to 30 years of age, increasing to 92% in
      subjects 46-60 years old. Above 60 years old, the prevalence decreased slightly.
      As a whole, the prevalence of infection did not increase significantly (p=0.147)
      with age. There were no significant differences in the prevalence of H. pylori
      infection, when patients were classified by age, smoking habit, educational
      level, alcohol consumption, the number of persons per room, the number of
      children per household, the number of adults per household, cup-sharing,
      household pets, toilet location, number of persons per bed and medical history of
      antibiotic and raw vegetable ingestion. In conclusion, no risk factors associated
      with infection was found in these adults, suggesting that the infection, even in
      a poor population, may be acquired predominantly during childhood; the relatively
      high prevalence that we observed may be more due to a cohort effect than to
      acquisition of infection during adulthood.

PMID- 16410893
TI  - Prevalence, susceptibility profile for fluconazole and risk factors for
      candidemia in a tertiary care hospital in southern Brazil.
AB  - Bloodstream infections caused by yeast, Candida spp, are quite important
      clinically and epidemiologically due to a high mortality rate and an increasing
      number of non-albicans species with a more resistant (differentiated
      susceptibility) profile. We examined species prevalence and susceptibility
      profile for fluconazole and the risk for nosocomial infections by Candida spp at
      the Hospital de Clinicas de Porto Alegre, a general tertiary care hospital in
      southern Brazilian, through a retrospective study, beginning with positive
      cultures of hospitalized patients. The distribution by species in 131 documented
      episodes was as follows: Candida albicans (45%), C. parapsilosis (24.4%), C.
      tropicalis (15.3%), C. glabrata (6.9%), C. krusei (4.6%) and 3.8% other species
      (C. pelicullosa, C. guilliermondii, C. lusitaniae and C. kefyr). The vast
      majority of samples (121- 92.4%) were susceptible to fluconazole; the resistant
      or dose-dependent sensitive samples included only C. krusei and C. glabrata.
      Blood diseases (leukemia, lymphoma), or neoplasias (solid tumors), were found in
      35.0% of the candidemia episodes. We noted the previous use of antibiotics in 128
      (97.7%) patients, with 79.7% using three or more antibiotics before the
      candidemia episode. Other risk factors included a central venous catheter in 94
      (71.8%) and abdominal surgery in 32 (24.4%) patients. The overall mortality rate
      was 51.9%, which varied according to the underlying disease. We found that C.
      albicans was the most prevalent species, although the non-albicans species
      predominated. However, in vitro resistance to fluconazole was detected only among
      the species (C. glabrata and C. krusei) that tend to be resistant to the azolic
      compounds. Previous use of antibiotic and the use of a central venous catheter
      were the main risk factors among patients with candidemia.

PMID- 16410894
TI  - Cutaneous periumbilical purpura in disseminated strongyloidiasis in cancer
      patients: a pathognomonic feature of potentially lethal disease?
AB  - Cutaneous manifestations in disseminated strongyloidiasis are infrequent but
      should raise the suspicion for its diagnosis. We retrospectively evaluated the
      charts of six patients with cancer and a proven diagnosis of disseminated
      strongyloidiasis. All patients had received prophylaxis with albendazole before
      starting antineoplastic therapy, which included high-dose steroids. They
      presented with septic shock, acute respiratory failure and characteristic
      purpuric periumbilical skin lesions. Strongyloides larvae were identified in
      tracheal aspirates (n=5), gastric aspirates (n=4), lung (n=2) and skin biopsies
      (n=2). All patients died despite antihelminthic therapy and intensive care
      support.

PMID- 16410895
TI  - Acute respiratory distress syndrome due to vivax malaria: case report and
      literature review.
AB  - Severe pulmonary involvement in malaria has been frequently reported in cases of
      Plasmodium falciparum infection, but rarely in vivax malaria. Among the 11
      previous cases of vivax-related severe respiratory involvement described in the
      literature, all except one developed it after the beginning of anti-malarial
      treatment; these appear to correspond to an exacerbation of the inflammatory
      response. We report the case of a 43-year-old Brazilian woman living in a malaria
      endemic area, who presented acute respiratory distress syndrome (ARDS) caused by
      P. vivax before starting anti-malarial treatment. The diagnosis was made based on
      microscopic methods. A negative rapid immunochromatographic assay, based on the
      detection of Histidine Rich Protein-2 (HRP-2) of P. falciparum, indicated that
      falciparum malaria was unlikely. After specific anti-plasmodial therapy and
      intensive supportive care, the patient was discharged from the hospital. We
      conclude that vivax malaria-associated ARDS can develop before anti-malarial
      therapy.

PMID- 16410896
TI  - Proceedings of the II International Symposium on Oncovirology (November 18-20,
      2004) at Sol Victoria Marina Hotel, Salvador, Bahia, Brazil. Implementation of a
      Training Program on Oncovirology in Bahia.

PMID- 16410917
TI  - Nitric oxide levels are not changed in saliva of patients infected with hepatitis
      C virus.
AB  - The aim of this investigation was to determine nitric oxide metabolite levels in
      saliva samples from hepatitis C virus-positive patients in an attempt to test the
      hypothesis if increased levels of nitric oxide metabolites correlates with the
      presence of HCV-RNA in saliva. Saliva of 39 HCV-positive patients and 13 HCV
      negative patients, without clinical or laboratorial evidence of liver disease
      were tested for nitric oxide metabolites. HCV-RNA was detected in serum and
      saliva by a RT-PCR method and nitric oxide level was determined by evaluation of
      its stable degradation products, nitrate and nitrite. No differences were found
      between the concentration of nitrite in saliva from HCV patients and controls, in
      despite of the presence or not of HCV RNA in saliva. Patients with HCV and
      cirrhosis had higher concentrations of nitrite but not significantly different
      from the control group or the groups of anti-HCV patients without cirrhosis.
      Increased levels of nitrite were not detected in anti-HCV positive patients, an
      indirect indication that chronic sialoadenitis are infrequent in these patients
      or occurs with low intensity not sufficient to increase nitric oxide metabolite
      levels in saliva.

PMID- 16410918
TI  - Risk factors for Leishmania chagasi infection in an urban area of Minas Gerais
      State.
AB  - In order to understand the determinants of human infection by Leishmania chagasi
      in an urban area, a cross-sectional population based study was conducted using
      molecular and serologic methods to identify infection. Participants were
      interviewed using a pre-coded questionnaire. Two criteria were tested to identify
      risk factors: Model 1--including all participants positive in hybridization by
      Leishmania donovani complex probe; Model 2--including all participants positive
      for hybridization and at least one serologic test. In Model 1, the variables
      associated with infection were: ownership of birds, time spent outside house
      between 6:00-10:00 PM and garbage not collected. In Model 2, the variables
      associated with infection were: family with knowledge of the vector, garbage not
      collected, garbage not removed or buried, ownership of birds and eroded areas in
      the neighborhood. The risk factors identified were associated with household
      conditions, presence of animals and the likelihood of contact with phlebotomine
      sandflies.

PMID- 16410919
TI  - Significance of bile-duct changes in schistosomiasis.
AB  - Lesions involving the intra-hepatic biliary ducts in schistosomiasis have been
      reported in the literature, both in mice and man, but there are no data
      concerning their quantitative, evolutionary or post curative chemotherapeutic
      aspects on record. In order to obtain such data an investigation on this subject
      was attempted. Mice infected with 50 Schistosoma mansoni cercariae were submitted
      to a liver biopsy at the 9th week post-infection, and treated with 400 mg/bw
      praziquantel immediately afterwards. Infected and non-infected controls were
      submitted to the same procedures. By 19 weeks from cercarial exposure all
      surviving animals were sacrificed. The biliary ducts were counted on histological
      sections and the results were expressed as biliary ducts/portal spaces. This
      quantitative evaluation was compared with that from normal controls and revealed
      hyperplasia as the main biliary duct change (p<0.007) in schistosomiasis.
      Hyperplastic changes underwent only mild partial and not statistically
      significant regression after specific chemotherapy (p>0.05). Infected and
      untreated animals presented ductal changes that did not differ from those of the
      treated group. Measurements of serum bilirubin (total and direct), and gamma
      glutamyl-transpeptidase (gamma-GT) did not reveal significant differences when
      animals from the several groups were compared. Thus, bile ducts exhibit a
      proliferative response in relation to neighboring S. mansoni injury to portal
      areas, but although these lesions are histopathologically impressive, they lack a
      functional or prognostic significance.

PMID- 16410920
TI  - Prevalence and incidence of Mycobacterium tuberculosis infection in nursing
      students in Vitoria, Espirito Santo.
AB  - This prospective study evaluated the incidence of Mycobacterium tuberculosis
      infection among nursing students at the Federal University of Espirito Santo,
      using the purified protein derivative test. In parallel, we evaluated whether
      knowledge on tuberculosis transmission mechanisms had any impact on nursing
      students' attitudes in relation to the risk of tuberculosis infection. The
      incidence of tuberculin conversion was 10.5% per year (p=0.035, 95% CI = 3.63
      17.43), whereas the expected conversion rate in the overall population in Brazil
      is 0.5% per year. These results indicate nursing students as a group at risk for
      TB infection. Among the risk factors studied only the use of NIOSH95 masks was
      associated with protection against infection (RR=0.2). Furthermore there was no
      statistical difference among students that PPD converted and those who remained
      negative regarding disease knowledge and the existence of adequate facilities for
      patient hospitalization. Our data reinforces the need for implementing special
      biosafety programs targeting this professional group.

PMID- 16410921
TI  - [Epidemiological, clinical and parasitological aspects of Chagas' disease in Mato
      Grosso do Sul State].
AB  - With the objective of evaluating epidemiologic, clinical and parasitologic
      aspects of chronic Chagas' disease in patients from the University Hospital of
      the Federal University of Mato Grosso do Sul, a cross-sectional study was
      performed with groups of 120 chagasic and non-chagasic patients aged from 16 to
      82 years. Epidemiologic aspects were evaluated by means of a questionnaire,
      cardiopathy by clinical examination, conventional electrocardiogram, radiology
      and Doppler echocardiograms (only in chagasic patients) and the presence of
      Trypanosoma cruzi in the blood stream by way of xenodiagnosis and polymerase
      chain reaction test. The results obtained indicated that the chagasic patients
      are predominantly alloctones with low-grade schooling, and were exposed to
      triatomines. The frequency of spontaneous abortion was higher in chagasic women.
      Chronic chagasic cardiopathy, estimated to occur in 20.2% of the patients, showed
      7.5% cardiomegaly, 6.2% aneurysm of the left ventricle, and with a predominance
      of dyspnea, palpitations and arterial hypertension. Xenodiagnosis was positive
      for 26.1% of the chagasics and the PCR was positive for 53.7%, and was
      significantly higher in males and alloctones. An analysis of the results shows
      that Chagas' disease, in the group studied, presented clinical and parasitologic
      characteristics demonstrating significant regional differences.

PMID- 16410922
TI  - [Epidemiology of the injuries caused by Thalassophryne nattereri (niquim) in
      Ceara State (1992-2002)].
AB  - In Ceara State (1992 to 2002) 16 cases of envenomation by Thalassophryne
      nattereri occurred in the seaside of Ceara, 87.5% of cases in the region of
      Fortaleza and 12.5% in the interior of Ceara State. Ninety four percent were men
      and 6% women. Age range: 75% between 21 and 40 years and 19% between 41 and 60
      years old. The time between medical assistance and the accident varied from 1 to
      5 hours (4 cases), 6 to 12 hours (3 cases), over 12 hours in 4 cases and 5
      patients did not know. Clinical manifestations observed were pain, local edema,
      transitory ischemia, paresthesia, ecchymosis and burned skin sensation. Anti
      inflammatory and analgesic drugs were used. In some cases, anesthetic, hot water,
      surgical peeling and anti-histaminic drugs were used. In 75% of cases cure was
      confirmed and in 12% cure was not confirmed. The number of accidents is probably
      higher than was found due to subnotification.

PMID- 16410923
TI  - Cytokine serum levels in patients infected by human immunodeficiency virus with
      and without Trypanosoma cruzi coinfection.
AB  - This study assessed the number of CD4 T lymphocytes, the parasitemia and serum
      levels of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha),
      interleukin-1 (IL-1), IL-4 and IL-10 of patients infected by human
      immunodeficiency virus (HIV) and human immunodeficiency virus/Chagas' disease
      coinfection. CD4 T lymphocytes were low in the two groups of patients, although
      significantly lower in patients without Chagas' disease. Serum levels of IFN
      gamma, IL-4 and TNF-alpha were significantly higher in patients with HIV/Chagas'
      disease. IL-4/IFN-gamma ratios were higher in patients with HIV/Chagas' disease,
      which showed a clear balance in favor of Th2-like cytokines in this group of
      patients. This Th2 balance was higher in patients with detectable parasitemia. We
      conclude that, although immunosuppression was observed, with CD4 T lymphocytes
      below 200/microm3, these patients did not display reactivation of T. cruzi
      infection and that a balance favorable to Th2 was associated with the presence of
      parasitemia.

PMID- 16410924
TI  - [Hepatitis B and C serologic markers in blood donors of the Ribeirao Preto Blood
      Center].
AB  - The investigation involved 25,891 blood donors who attended for the first time
      the Blood Center of Ribeirao Preto, Brazil, between Jun 23, 1996 and Jun 22,
      2001. The objective was to study the proportion of positive serological markers
      for hepatitis B and C at the initial screening tests and to estimate the
      prevalence of such infections through the analysis of confirmatory tests, carried
      out at the University Hospital as a part of the patients evaluation. Data from
      the donors and laboratory results were obtained from the records of both the
      Blood Bank and the Hospital. The population of donors was mainly composed by
      males (83.6%) and by individuals between 26 and 45 (64%) years of age. The
      proportions of positive results in screening tests were 0.6% (CI95%: 0.54-0.72)
      for HBsAg and 1.2% (CI95%: 1.02-1.28) for anti-HCV. Confirmatory testes showed
      values of prevalence of 0.2% (CI95%: 0.16-0.28) for hepatitis B and 0.3% (IC95%:
      0.24-0.38) for hepatitis C.

PMID- 16410925
TI  - [Laboratory diagnosis of rabies in the west region of Sao Paulo State].
AB  - The Polo da Alta Sorocabana laboratory, Presidente Prudente, SP, Brazil, and the
      Biological Institute in Sao Paulo State, performed an evaluation of rabies
      diagnosis from 1996 to 2003 in the west region of Sao Paulo State. For the tests,
      the laboratories used direct immunofluorescence and mice inoculation in 4,950
      samples, that were sent for analysis involving dogs, cats, cattle, chiroptera
      (bats) and other animals. According to the results, the laboratories found 74
      positive samples; of which 58 (78.4%) were non-hematophagous bats and 16 (21.6%)
      related to cattle. The present epidemiological study verified that in spite of
      the high positive index in chiroptera compared to the other species, there was
      not an outbreak of rabies in the species in the region of Presidente Prudente,
      from 1996 to 2003 but a rise in the positive index due to a marked increase in
      the number of chiroptera samples sent to the laboratories for virus rabies
      research.

PMID- 16410926
TI  - Prevalence of hepatitis C virus infection and HCV genotypes among hemophiliacs in
      the State of Bahia, Northeastern Brazil: analysis of serological and virological
      parameters.
AB  - The objective of the present study was to analyze HCV serological and virological
      parameters from hemophiliacs in the State of Bahia. Anti-HCV was investigated by
      ELISA in a cohort of 268 hemophiliacs A/B who were followed-up in a reference
      unit for hemotherapy in the State of Bahia. HCV viremia and genotypes were also
      determined from a subset of 66 anti-HCV seropositive hemophiliacs. Seroprevalence
      among hemophiliacs was 42.2% (95% CI 36.5-48.1) and was significantly higher
      (p<0.05) according to age > or =10 years, presence of factor VIII/IX inhibitory
      antibodies and other infection markers. None of the hemophiliacs less than 5
      years of age were anti-HCV seropositive. Viremia was detectable in 77.3% (51/66).
      HCV genotype 1 (74%) was the most prevalent followed by genotype 3 (22%) and
      genotype 2 (4%). Our results indicate that HCV prevalence is still high among
      hemophiliacs, although HCV transmission was not observed in young hemophiliacs.

PMID- 16410927
TI  - [Chromobacteriosis in Ilheus, Bahia: epidemiologic, clinical and laboratorial
      investigation].
AB  - In April/2004, a group of people traveled to a farm in a town in the south of
      Bahia and afterwards, three teenagers from the same family developed symptoms of
      severe septicemia and two died. The Health Department carried out an
      epidemiologic, clinical, laboratory and environmental investigation that resulted
      in the identification of Chromobacterium violaceum, in biological material from
      one of them, water and soil. This is the first report of the disease in Bahia
      State.

PMID- 16410928
TI  - [Fever of unknown origin in adults].
AB  - Fever of unknown origin has been defined as axillary temperature higher than 37.8
      degrees C on several occasions, persisting without diagnosis for at least 3 weeks
      in spite of at least 1 week's investigation in hospital. Lately, the definition
      has been modified and extended to reflect evolutionary changes in clinical
      practice. In response to this new evolving environment, cases of fever of unknown
      origin are currently classified as: classic, nosocomial, in neutropenia, and
      human immunodeficiency virus-related. The objective of our review was to try and
      define and to update the information on the subject.

PMID- 16410929
TI  - [Regression of hepatic fibrosis].
AB  - Extensive and persistent hepatic fibrosis has for a long time been considered
      irreversible. However, recent studies on the behavior of hepatic fibrosis,
      especially those related to evolution and involution of advanced schistosomiasis
      in man, have challenged this concept, and nowadays it is becoming clear that any
      type of fibrosis is reversible, including that associated with hepatic cirrhosis.
      The problem consists in identifying and eliminating its cause. Although fibrosis
      in the liver has little functional significance by itself, its severity derives
      from associated vascular changes. However, new data on fibrosis regression
      indicate that disappearance of fibrosis is usually accompanied by remodeling of
      vascular changes. But, there are peculiarities related to the anatomic type of
      fibrosis and to its functional significance, which suggest that sometimes
      fibrosis may indeed be irreversible. These aspects, some of which in need of
      further studies, are presented and discussed herein.

PMID- 16410930
TI  - [Cholelithiasis associated with the use of ceftriaxone].
AB  - A seven-year-old boy treated with ceftriaxone for meningitis who presented a
      right upper quadrant abdominal pain associated with cholelithiasis. After three
      months he was symptom-free and abdominal ultrasonography was normal. Awareness of
      this phenomenon is highly important and can save many unnecessary
      cholecystectomies.

PMID- 16410931
TI  - [Enteroparasitosis prevalence in food handlers, Florianopolis, SC].
AB  - We analyzed 238 feces samples in two populations of individuals in the city of
      Florianopolis, Santa Catarina State, Brazil: we selected workers in a fast food
      company and workers in street markets and vegetable and fruit markets. The
      intestinal parasites were high in these food handlers.

PMID- 16410932
TI  - [Evaluation of the ocular globe compression sign in infectious meningeal
      syndromes].
AB  - Infectious meningeal syndromes represent a serious medical emergency whose
      clinical-epidemiologic diagnosis must be immediately established for early
      initiation of appropriate treatment. However, in many cases data from the
      clinical exam are insufficient to confirm or rule out the diagnosis. Therefore,
      the aim of this work was to assess the value of the ocular globe compression sign
      in 57 patients with suspicion of infectious meningeal syndrome, both male and
      female and aged four years or older. The sensitivity (34.5%), specificity (78.6%)
      and positive (62.5%) and negative (53.7%) predictive values of ocular globe
      compression sign were similar to nuchal rigidity, and the agreement between two
      independent observers was fair (Kappa=0.65). Ocular globe compression sign in
      conjunction with other findings of the clinical examination could be of great
      value in the diagnostic process of patients with infectious meningeal syndromes.

PMID- 16410933
TI  - [Epidemiologic survey of teniasis in Health and Family Program in Uberaba, MG].
AB  - An epidemiologic survey was carried out on 110,144 people from the Health Family
      Program to evaluate some Epidemiologic aspects of teniasis. Previous history of
      passing proglottides was registered in 185 (0.2%) of them, and 112 (60.5%)
      received praziquantel. After this 97 (86.6%) passed proglottides characterized as
      Taenia Saginata and Taenia Solium in 36 (37.1%) and 4 (4.1%) respectively.

PMID- 16410934
TI  - [Monitoring of pregnant women with toxoplasmosis in Public Health Services].
AB  - The monitoring of 290 pregnant women with suspicion of acute toxoplasmosis
      attended by Public Health Services is discussed. In 69% a single test (Elisa-IgM)
      led to the treatment. Of 112 treated, the system did not offer any drug to 24%.
      In 12.1% there was a progressive increase of IgM and IgG. In 48.2% the treatment
      was begun thirty days after the laboratorial diagnosis.

PMID- 16410935
TI  - [Observations on the use of TESA blot for the serological diagnosis of Chagas'
      disease].
AB  - TESA blot was compared with indirect hemagglutination, indirect
      immunofluorescence and ELISA tests. In sera from 30 participants infected with
      Trypanosoma cruzi, and in 30 non infected the four techniques produced entirely
      equivalent results, all positive and all negative, respectively. In cases
      admitted to be inconclusive or in visceral leishmaniasis, frequent false
      positives were detected. However, TESA blot contributed with the least proportion
      of them.

PMID- 16410936
TI  - Solitary pulmonary nodule caused by Schistosoma mansoni in a patient with
      medullary thyroid carcinoma.

PMID- 16410937
TI  - [OPS/MSF Regional Consultation Technique on Organization and Structure of the
      Medical Attention of patient with Chagas disease].

PMID- 16410938
TI  - Should tenofovir ever be used in association with didanosine?

PMID- 16410939
TI  - Adherence to an occupational blood borne pathogens exposure management program
      among healthcare workers and other groups at risk in Argentina.
AB  - We conducted a retrospective review of 130 occupational blood borne pathogens
      exposure (BBP-OE) records at Centro de Estudios Medicos e Investigaciones
      Clinicas, a university hospital with an ongoing educational program and a
      postexposure management program for healthcare workers (HCWs) since 1995, in
      order to evaluate adherence to a hospital BBP-OE management program. We compared
      HCWs from our institution (Group 1) and HCWs from independent institutions that
      contract our postexposure management program (Group 2). Compliance with standard
      precautions in Group 1 was inadequate in 77%, 23%, and 16% of nurses, physicians,
      and others, respectively. A greater proportion of HCWs in Group 1 (74% vs. 40%)
      reported occupational accidents within two hours after exposure (p = 0.0001). No
      difference was observed regarding compliance with adherence to schedule, partial
      adherence, and loss at follow-up (14%, 33%, and 53%; p > 0.05). Adherence to the
      standard of care for BBP-OE, including postexposure prophylaxis, was low (HIV:
      53% and HBV: 63%). Knowledge of the seropositive status of the source patient did
      not improve adherence. We conclude that postexposure programs do not guarantee
      appropriate behavior by HCWs. General interventions and ongoing personnel
      education to modify individual attitudes are needed, as are continued efforts to
      assess HCWs' experiences with these programs, as well as the identification of
      strategies to improve adherence.

PMID- 16410940
TI  - Prevalence of Mycobacterium avium and Mycobacterium tuberculosis in blood
      cultures of Brazilian AIDS patients after introduction of highly active
      retroviral therapy.
AB  - The use of highly active antiretroviral therapy (HAART) for the treatment of HIV
      infection has been associated with a marked reduction in the incidence of most
      opportunistic infections. From April 2001 to February 2002, 80 blood samples from
      patients who were suspected to have disseminated mycobacterial infection,
      presenting fever and (preferably) a CD4 T cell count < 100.0 cell/mL were
      investigated. Twelve (15%) of the 80 blood cultures were positive for
      mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and
      M. tuberculosis in 5 (6.2%). The TCD4+ count at the time of M. avium bacteremia
      ranged from 7 cells/microL (average of 48.5 cell/microL), while in M.
      tuberculosis bacteremia it ranged from 50.0 cells/microL (average of 80.0
      cell/microL). The prevalence of M. avium bacteremia in our study follows the
      expected decline in opportunistic infections observed after the introduction of
      HAART; however, mycobacteremia by M. tuberculosis still indicates a high
      prevalence of tuberculosis infection in AIDS patients.

PMID- 16410941
TI  - Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary
      hospital in Sao Paulo - Brazil.
AB  - Tuberculosis (TB)/HIV co-infection significantly changes the natural history of
      both diseases. Proper comprehension and clinical management of co-infected TB/HIV
      patients is still a challenge, particularly in places like Brazil, where both
      types of infection are prevalent. OBJECTIVES: Evaluate the frequency of the
      clinical forms of TB in HIV-infected patients; correlate the clinical forms of TB
      with the level of immunodeficiency; evaluate the response to therapy with
      different regimens for the treatment of TB; identify potential prognostic factors
      in TB/HIV patients. MATERIAL AND METHODS: The following data were collected at
      the beginning of the study: medical history, epidemiological background, physical
      examination, and laboratory evaluation (complete blood cell count, T lymphocyte
      subsets, viral load and tuberculin test). Monthly clinical follow-up was
      performed, with attention to adverse reactions to tuberculostatic drugs.
      TCD4+/CD8+ lymphocyte counts and quantification of the viral load were performed
      after 2, 4, 6, 10 and 15 months of follow-up. RESULTS: The study population
      consisted of 78 patients (45 males and 33 females) and their mean age was 36.4 +/
      7.9 years The mean TCD4+ count values were higher in patients with the cavitary
      pulmonary form and lower in patients with disseminated forms. There were no
      significant differences in the mean TCD8+ cells counts . in the different
      clinical forms of TB. However, the mean laboratory values for hemoglobin,
      hematocrit and leucocytes at study entry did differ significantly among the
      various clinical forms of TB. At the end of the trial, the Tb recovery rate was
      of 78%, with four cases (5%) of treatment failure, eight (11%) treatment
      discontinuations and five deaths (6.4%). The highest rate of treatment failure
      (75%) was observed among patients with the disseminated form. Lower TCD4+ mean
      values were observed in cases of treatment failure and death. There was a
      correlation between the TCD4+ cell values and the TB outcome at the six time
      points. TCD8+ (cells/mm(3)) mean values assessed at the six time points in
      relation to the TB outcome indicated (non-significantly) lower values in patients
      who progressed to treatment failure. Considering the different TB outcomes, there
      was a significant correlation between TCD8+ values at the first and third
      assessments. Lower mean values of hemoglobin, hematocrit, platelet and leukocytes
      were observed among the cases of treatment failure than in patients who
      recovered. The variables hemoglobin, hematocrit, leukocytes and platelets were
      significantly different among the groups. CONCLUSIONS: The pulmonary forms of TB
      were most frequent in HIV infected patients; the extrapulmonary, associated and
      disseminated forms were predominantly seen in patients with a more severe level
      of immunosuppression. The TB recovery rate in HIV infected patients was similar
      to the expected rate in non-infected individuals. The best results were obtained
      when regimens containing rifampicin were used. Pancytopenia and low levels of
      TCD4+ and TCD8+ lymphocytes at the initial time point of the study were
      correlated with an unfavorable outcome of TB, and therefore they can be
      considered potential prognostic factors. However, the of TCD8+ lymphocyte values
      were the most important variable assessed.

PMID- 16410942
TI  - Evaluation of AIDS-related disability in a general hospital in southern, Brazil.
AB  - The increase in survival rates of patients affected by AIDS is associated with
      physical disabilities that can compromise their functional independence. We
      examined the degree and types of disabilities in hospitalized AIDS patients , as
      well the clinical and immunological parameters associated with disability. The
      lowered functional status was associated with increased time since AIDS had been
      diagnosed, with complaints of weakness, and with the involvement of more than one
      set of systems in the definition of AIDS. The inability to perform daily living
      activities was associated with higher viral loads (log) c/mL, lower CD4+/mL and
      CD4+/CD8+ ratios, and with involvement of the central nervous system, in the
      cause of hospitalization. Both the inability to perform daily living activities
      and low functional status were associated with muscle strength alteration and
      with being unemployed.

PMID- 16410943
TI  - Estimation of the residual risk for the transmission of HIV in blood donors from
      the mountain region of Santa Catarina.
AB  - The HIV, in hemotheraphy, may be transmitted by erythrocyte, platelets,
      crioprecipitated, frozen fresh plasma and possibly, by other blood components.
      Appropriate legislations for this new reality were elaborated normatizing the
      hemotheraphy practices in Brazil, creating a set of procedures and actions aiming
      at guaranteeing the quality of the blood, during the whole process. However, the
      residual risk remains, and it can be calculated as a product of the incidence and
      period of the immunological window. The objective [corrected] of the present
      study was to determine the rate of residual risk of the HIV blood transmission,
      in the blood donors from the Mountain Region of Santa Catarina. In order to
      calculate the residual risk of the HIV markers, 4,857 donors of repetition from
      the 24,969 individuals who donated blood from 2000 to 2003 were evaluated, and
      the results showed a serumconversion, in one case. The method used to calculate
      the residual risk followed the model of the immunological incidence window used
      by Schreiber (1996), in the USA. A estimate risk of 1:50,000 was verified. The
      case was considered as confirmed when one of the HIV, in the Hemocenter, is
      considered one of the HIV markers, in 1:50.000, which confirms the hypothesis
      that the new legislation related to the Blood National Politics, with the
      introduction of more sensible tests is decreasing the immunological window,
      diminishing the residual and, consequently, intensifying the transfusion
      security.

PMID- 16410945
TI  - HIV frequency among female sex workers in Imbituba, Santa Catarina, Brazil.
AB  - We examined HIV frequency and probable risk factors among female sex workers in
      the port city of Imbituba, Southern Brazil. From December 2003 through February
      2004, 90 female sex workers were interviewed in order to investigate demographic,
      socioeconomic and behavioral variables related to HIV infection. A blood sample
      of each woman was also collected to test for HIV antibodies. Six (6.7%) of the
      sex workers were HIV-positive; the significantly-correlated risk factors were the
      daily number of clients (p = 0.008), the use of inhaled illicit drugs by the sex
      workers (P = 0.053) and by their clients (p = 0.005), and the lack of condom use
      in sexual relations (p = 0.015). The HIV infection rate in these sex workers was
      higher than that in the general population and similar to that found in other
      studies made with Brazilian populations presenting the same characteristics. This
      highlights the need for preventative measures, especially in this port area, in
      order to reduce transmission and to deter the introduction and dissemination of
      HIV.

PMID- 16410944
TI  - Lack of effect of motivation on the adherence of HIV-positive/AIDS patients to
      antiretroviral treatment.
AB  - As a result of the potent drug combinations of reverse transcriptase inhibitors
      and protease inhibitors currently available, it is now possible to achieve
      extreme reductions in the numbers of viral particles in the peripheral blood of
      HIV-positive patients undergoing treatment, to the point that they are
      undetectable. Moreover, the immunological recovery resulting from continued and
      prolonged use of these drugs significantly reduces both mortality and the
      incidence of opportunistic infections. However, the strict therapeutic regimens
      required, the number of pills, adverse events and the stigma of a disease that
      requires the patient to introduce pill-taking into his/her lifestyle brings into
      question one aspect of mental health, which is motivation to do that which is
      being proposed. We investigated the influence of each of the components of the
      adherence trilogy: information, motivation and behavioral abilities, as risk
      factors in a population of HIV-positive/AIDS patients undergoing antiretroviral
      treatment in the city of Salvador, Bahia, Brazil. MATERIAL AND METHODS: An
      intervention study was carried out by introducing motivational assistance into
      the routine recommendations for the treatment of patients who were initiating
      antiretroviral (ARV) therapy. Seventy-six treatment-naive patients, who had been
      selected to initiate ARV therapy, were included. These patients were divided into
      two groups. Group A, in which the regular routine of the institution was
      followed, received information on the disease and its treatment;patients in group
      B had the same routine, but they were also followed-up fortnightly and given
      motivational intervention. Evaluations of viral load and CD4 count before and
      following treatment were used to measure adherence. RESULTS: There was no
      significant difference between the two groups. CONCLUSIONS: As the rates of non
      adhesion were at the lower limits of the ranges reported in the literature, it
      would appear that providing motivation and information can be of help to the
      patient.

PMID- 16410946
TI  - Prevalence of indeterminate human immunodeficiency virus western blot results in
      pregnant women attended at a public hospital in Presidente Prudente, Brazil.
AB  - The AIDS epidemic is spreading rapidly among women worldwide, offering increasing
      opportunities for vertical transmission of HIV. In Brazil, the prevalence of HIV
      infection among pregnant women is less than 1%. Therefore, the positive
      predictive value of an HIV EIA test tends to be lower than the more frequent
      indeterminate Western blot result. Pregnant women receiving antenatal care, from
      2000 to 2004, at a public secondary hospital in the city of Presidente Prudente,
      Sao Paulo, Brazil, were systematically screened for HIV by means of two distinct
      EIA tests, in order to determine the prevalence of indeterminate Western blot
      results among pregnant women showing discordance in both HIV EIA tests and
      indirect immunofluorescence assay. Confirmatory indirect immunofluorescence was
      performed on material for all women with positive results in both EIA tests.
      Whenever there were positive results in EIA and IIA, the applicant was retested
      by the initial screening assay. Only those not showing concordance in results in
      EIA and IAA had a Western blot performed. The viral load was measured in pregnant
      women with positive or indeterminate Western blot results. Out of 9,786 sera, 105
      (1.0%) were positive in the two HIV EIA screening tests, confirmed by indirect
      immunofluorescence. Among these women, Western blot was interpreted as
      indeterminate in 11 (0.1%) cases and their viral load was <50 copies/mL. We found
      a prevalence of 0.1% HIV indeterminate Western blots in pregnant women from
      Presidente Prudente and the surrounding region; none of these pregnant women had
      positive HIV viral loads.

PMID- 16410947
TI  - Spontaneous neutrophil activation in HTLV-1 infected patients.
AB  - Human T cell lymphotropic Virus type-1 (HTLV-1) induces lymphocyte activation and
      proliferation, but little is known about the innate immune response due to HTLV-1
      infection. We evaluated the percentage of neutrophils that metabolize Nitroblue
      tetrazolium (NBT) to formazan in HTLV-1 infected subjects and the association
      between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was
      collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1-
      associated myelopathy); 22 healthy individuals were evaluated for spontaneous and
      lipopolysaccharide (LPS)-stimulated neutrophil activity (reduction of NBT to
      formazan). The production of IFN-gamma and TNF-alpha by unstimulated mononuclear
      cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN
      gamma and TNF-alpha production, were significantly higher (p<0.001) in HTLV-1
      infected subjects than in healthy individuals. A trend towards a positive
      correlation was noted, with increasing percentage of NBT positive neutrophils and
      levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had
      significantly greater NBT than healthy controls, 43+/-24% and 17+/-4.8%
      respectively (p< 0.001), while no significant difference was observed between
      healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30+/-20%).
      Spontaneous neutrophil activation is another marker of immune perturbation
      resulting from HTLV-1 infection. In vivo activation of neutrophils observed in
      HTLV-1 infected subjects is likely to be the same process that causes spontaneous
      IFN-gamma production, or it may partially result from direct IFN-gamma
      stimulation.

PMID- 16410948
TI  - Record linkage and capture-recapture estimates for underreporting of human
      leptospirosis in a Brazilian health district.
AB  - Record linkage and capture-recapture models were used to estimate the number of
      cases of human leptospirosis in the health district of Santa Maria, RS in
      southern Brazil. Twelve months of laboratory, hospital and epidemiological
      surveillance data were matched by name, age, residence and the month of
      diagnosis. Only laboratory-confirmed cases were considered. The record linkage
      revealed more than 20 times more cases than the official estimate for the health
      district, indicating a leptospirosis epidemic, with an annual incidence of more
      than 3 per 1,000 inhabitants and a case fatality of 0.37%. Severe cases were
      predominantly found through hospital records, overlapping to some extent with the
      epidemiological surveillance data, whereas less severe cases were found almost
      exclusively through laboratory logs. Different combinations of data sources
      influenced the detection rate for low versus high severity cases. Based on log
      linear capture-recapture models, stratified by case severity and taking into
      account possible dependencies between the data sources, an insignificant number
      of cases were missed by all sources.

PMID- 16410949
TI  - Double-stranded RNA viral infection in Cuban Trichomonas vaginalis isolates.
AB  - Trichomonas vaginalis can be infected with double-stranded RNA (dsRNA) viruses
      designated T. vaginalis virus (TVV), which may have important implications for
      trichomonal virulence and disease pathogenesis. We tested for TVV in 40 fresh T.
      vaginalis isolates from Cuban patients by total extraction of nucleic acids (DNA
      and RNA). TVV was detected in 22 (55%) of the 40 T. vaginalis isolates. This
      gives an estimate of the infection rate of Cuban T. vaginalis isolates by the
      dsRNA virus. Future research should focus on the association between
      trichomonosis symptoms and the presence of TVV.

PMID- 16410950
TI  - Clinical and epidemiological aspects of children hospitalized with severe
      rotavirus-associated gastroenteritis in Salvador, BA, Brazil.
AB  - Little is known about the epidemiology of severe rotavirus-associated
      gastroenteritis in Brazil. Given the morbidity associated with this condition and
      the importance of having detailed knowledge about the impact of rotavirus
      infection on the epidemiology of acute diarrhea in children, especially those
      with the most severe diarrheal conditions, we retrospectively reviewed the
      medical records of all pediatric patients admitted to a tertiary hospital in
      Salvador, Brazil, due to rotavirus-associated gastroenteritis during one year. It
      was observed that rotavirus was responsible for 15.6% of the hospitalizations
      caused by diarrhea and/or vomiting during the period of the study and that 87 of
      218 (39.1%) patients seen at the emergency room with rotavirus-associated
      gastroenteritis needed to be hospitalized, comprising the population of our
      study. Most patients presented signs of dehydration, and 41% of them had
      metabolic acidosis. Most patients (79%) were between six months and four years of
      age and 72% of the cases occurred in June and July. Gastrointestinal symptoms
      were rarely present at the beginning of the clinical presentation, and they
      normally did not last for more than one week.

PMID- 16410951
TI  - Acremonium kiliense infection in a child with chronic granulomatous disease.
AB  - Infection by unusual microorganisms can be one of the clinical manifestations of
      primary immunodeficiency (PID). We report on a four-month-old child with
      pneumonia caused by the fungus Acremonium kiliense as the first clinical
      manifestation of chronic granulomatous disease. We emphasize the importance of an
      active search for unusual organisms in immunodeficient patients, and a precise
      diagnosis and early institution of specific treatment against such microorganisms
      for the reduction of the morbidity and mortality of these patients.

PMID- 16410952
TI  - Application of molecular techniques in the study of Staphylococcus aureus clonal
      evolution--a review.
AB  - Staphylococcus aureus is an important agent of healthcare-associated and
      community-acquired infections. A major characteristic of this microorganism is
      the ability to develop resistance to antimicrobial agents. Several molecular
      techniques have been applied for the characterization of S. aureus in
      epidemiological studies. In the present review, we discuss the application of
      molecular techniques for typing S. aureus strains and describe the nomenclature
      and evolution of epidemic clones of this important pathogen.

PMID- 16410953
TI  - Patterns of antennal sensilla of Panstrongylus megistus from three Brazilian
      states.
AB  - The objective of the present study was to analyze and describe the phenotype of
      the antennal sensilla of Panstrongylus megistus, one of the epidemiologically
      most important species of triatomines in Brazil. Specimens from the Brazilian
      states of Goias (GO), Minas Gerais (MG), and Rio Grande do Sul (RS) were
      compared, based on studies of four types of sensilla on three antennal segments:
      thick-walled trichoid (TK), thin-walled trichoid (TH), bristles (BR), and
      basiconica (BA). Discriminant analysis allowed the separation of the RS specimens
      from those of GO and MG. Multivariate discriminant analysis demonstrated that the
      sensilla of males differed from those of females, the variables with greatest
      weight being the BA of all three segments and the TK of flagellum 1. The
      basiconica sensilla were significantly more abundant in females, on all three
      segments. Antennal sensilla patterns also demonstrated significant differences
      among P. megistus specimens.

PMID- 16410954
TI  - Infection by Mycobacterium leprae of household contacts of lepromatous leprosy
      patients from a post-elimination leprosy region of Colombia.
AB  - The Leprosy Control Program of Antioquia, (post-elimination leprosy state of
      Colombia), had registered by 1999, 56 lepromatous leprosy patients and their
      household contacts (HHC). Our interest was to detect Mycobacterium leprae
      infection in these HHC. Clinical examination, acid-fast bacillary staining (AFB)
      in nasal secretions, and slit skin samples, IgM anti-PGL-I in serum and Lepromine
      A (Mitsuda) reactivity were tested. Two hundred forty eight HHC were studied, 49%
      were male. After clinical examination, two HHC were diagnosed as multi bacillary
      patients; 13% showed positive IgM anti-PGL-I titers; Mitsuda reaction (> or = 4
      mm) was positive in 59%; AFB was negative in all samples, except in the two new
      patients. HHC were classified according to test results. Group 1: two new multi
      bacillary patients. Group 2: 15 HHC seropositive, Mitsuda-negative. Group 3: 13
      HHC seropositive, Mitsuda-positive. Group 4: 130 HHC seronegative, Mitsuda
      positive. Group 5: 88 HHC seronegative, Mitsuda-negative. These results are an
      indication that the transmission of the infection is still happening in a region
      considered in the post elimination phase. The two new patients represent an
      infection source for others contacts, and groups 2 and 3 are infected HHC that
      could develop the disease in future. Follow up of high risk population is
      necessary to achieve real elimination of leprosy.

PMID- 16410956
TI  - Serologic evidence of human metapneumovirus circulation in Uruguay.
AB  - First identified in 2001, the human metapneumovirus (hMPV), is a respiratory
      tract pathogen that affects young children, elderly, and immunocompromised
      patients. The present work represents the first serologic study carried out in
      Uruguay. It was performed with the purpose of obtaining serological evidence of
      hMPV circulation in Uruguay and to contribute to the few serologic reports
      described until now. Sixty nine serum samples collected between 1998 and 2001 by
      vein puncture from patients without respiratory symptoms or underlying pathology
      aged 6 days to 60 years were examined using an indirect immunofluorescence assay
      (IFA). The global seropositivity rate of the samples was 80% (55/69). Rates of
      60% (15/25) and 91% (40/44) were observed for the pediatric and adult cohorts,
      respectively. Results obtained from a longitudinal analysis of 6 children aged 6
      days to 18 months are discussed. These results are a clear evidence of hMPV
      circulation in Uruguay, at least since 1998, and reinforce the previous data on
      worldwide circulation of this virus.

PMID- 16410955
TI  - Prevalence and genetic diversity of astroviruses in children with and without
      diarrhea in Sao Luis, Maranhao, Brazil.
AB  - Human astroviruses (HAstV) have been increasingly identified as important
      etiological agents of acute gastroenteritis in children up to five years old. The
      aim of this study was to determine the prevalence and genotype diversity of HAstV
      in children with symptomatic and asymptomatic infections in Sao Luis, Maranhao,
      Brazil. From June 1997 to July 1999 a total of 183 fecal samples 84 from
      symptomatic and 99 from asymptomatic children were tested by enzyme immunoassay
      for HAstV. Prevalence rates were found to be 11 and 3% for symptomatic and
      asymptomatic children, respectively. Reverse transcription-polymerase chain
      reaction (RT-PCR) was carried out in 46 specimens (26 symptomatic and 20
      asymptomatic) including the 12 samples that were positive by enzyme immunoassay
      (EIA). The overall positivity yielded by both methods was 8% (15/184); of these,
      11% (9/84) for symptomatic and 5% (5/99) for those without symptoms or signs.
      Sequence analysis of amplicons revealed that HAstV-1 genotype was the most
      prevalent, accounting for 60% of isolates. Genotypes 2, 3, 4, and 5 were also
      detected, as one single isolate (10%) for each type. Variations in the sequences
      were observed when Brazilian isolates were compared to prototype strains
      identified in the United Kingdom. No seasonal pattern of occurrence was observed
      during these two years of study, and peak detection rate was observed in children
      aged between 3 and 6 months in the symptomatic group, and between 18 and 24
      months in the controls.

PMID- 16410957
TI  - Dispersal pattern of the sand fly Lutzomyia neivai (Diptera: Psychodidae) in a
      cutaneous leishmaniasis endemic rural area in Southeastern Brazil.
AB  - The dispersal pattern of the sand fly Lutzomyia neivai was studied through mark
      release-recapture experiments in an American cutaneous leishmaniasis endemic
      rural area in Southeastern Brazil. Over 6500 specimens were marked with
      fluorescent powder and released in forest edge and peridomicile habitats from
      August to November 1999, February and April 2000. Recapture attempts were made
      using Shannon and CDC traps up to eight successive nights after releases. A total
      of 493 (7.58%) specimens were recaptured. The number of recaptured males and
      females of L. neivai in CDC traps was not affected by the distance between the
      trap and the release points. Approximately 90% of males and females recaptured in
      CDC traps were caught up to 70 m from the release points. The maximum female
      flight range recorded was 128 m. The average flight range per day was less than
      60 m for males and females. Of the flies released in forest edge, approximately
      16% of the recaptured females were caught in Shannon traps in the peridomicile
      habitat. The results indicate that the movements of L. neivai are spatially focal
      and the possibility of dispersion from forest to peridomicile habitat may be an
      important way of contracting leishmaniasis in dwellings.

PMID- 16410958
TI  - Variation of snail's abundance in two water bodies harboring strains of
      Pseudosuccinea columella resistant and susceptible to Fasciola hepatica
      miracidial infection, in Pinar del Rio Province, Cuba.
AB  - The abundance of freshwater snails in two rural sites of Pinar del Rio, Cuba,
      which harbor Pseudosuccinea columella susceptible and resistant to miracidia of
      Fasciola hepatica was followed for one year. Susceptible snails were found in the
      most anthropic site (IPA) whereas the resistant population inhabited the most
      preserved one (El Azufre). Only two snail species coexisted with P. columella at
      IPA site (Physa cubensis and Tarebia granifera) while five species were found at
      El Azufre, including an endemic from that province (Hemisinus cubanianus).
      Populations of both resistant and susceptible snails showed stable densities
      throughout the year, although the susceptible strain attained higher abundance.
      The highest densities were observed in April-May 2004 for the susceptible
      population whereas the resistant strain attained its highest abundance in January
      2004. No record of Fossaria cubensis was made and the thiarid T. granifera
      occurred only at low densities. One of the sampled sites (IPA) meets all the
      conditions for the first report of P. columella naturally infected with larvae of
      F. hepatica.

PMID- 16410959
TI  - Predominance of Trypanosoma rangeli infection in children from a Chagas disease
      endemic area in the west-shore of the Panama canal.
AB  - A total of 206 serum samples from children (3-14 years old) living in the Amador
      County (La Chorrera District, Province of Panama) were screened by indirect
      immunofluorescence antibody test (IFAT) for the presence of antibodies against
      Trypanosoma cruzi. Positive sera were confirmed by recombinant enzyme-linked
      immunosorbent assay (ELISA) and Western blot analysis. The presence of blood
      trypanosomes was investigated by hemoculture and subsequently identify by a
      duplex polymerase chain reaction (PCR) followed by dot blot hybridization. The
      results indicated a prevalence of 9.7% for trypanosome infections, a
      seroprevalence of 2.9% against T. cruzi and a predominance of T. rangeli
      infection (6.8%). The immunological and clinical implications of these findings
      are discussed.

PMID- 16410960
TI  - Isolation and isoenzyme characterization of Leishmania (Viannia) braziliensis
      from a case of human cutaneous leishmaniasis in northeast centre of the state of
      Sao Paulo.
AB  - The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made
      without the species identification of the Leishmania, even in areas without
      previous epidemiological surveys. Here we report the isolation of a Leishmania
      strain from a patient of Rincao, state of Sao Paulo, that was identified by
      isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections
      were made in the area where the patient live in order to investigate the likely
      vector species.

PMID- 16410961
TI  - First report of Lymnaea cousini Jousseaume, 1887 naturally infected with Fasciola
      hepatica (Linnaeus, 1758) (Trematoda: Digenea) in Machachi, Ecuador.
AB  - We report the first finding of Lymnaea cousini naturally infected with Fasciola
      hepatica in Ecuador. A sample of 70 snails was collected in April 2005 from a
      wetland located in a valley at approximately 3000 m a.s.l., near the locality of
      Machachi, Pichincha Province. The prevalence of natural infection in L. cousini
      was 31.43%, which is the highest value ever recorded for naturally infected
      lymnaeid species.

PMID- 16410962
TI  - Occurrence of co-infection by Leishmania (Leishmania) chagasi and Trypanosoma
      (Trypanozoon) evansi in a dog in the state of Mato Grosso do Sul, Brazil.
AB  - A natural case of co-infection by Leishmania and Trypanosoma is reported in a dog
      (Canis familiaris) in south- western state of Mato Grosso do Sul, Brazil. Both
      amastigote and trypomastigote forms were observed after Giemsa staining of
      cytological preparations of the dog's bone marrow aspirate. No parasite was
      detected using medium culture inoculation of the sample. DNA obtained from the
      bone marrow aspirate sample and from the blood buffy coat was submitted to
      polymerase chain reaction (PCR) with a set of rDNA-based primers S4/S12. The
      nucleotide sequence of the PCR product was identical to that of Trypanosoma
      (Trypanozoon) evansi. The S4/S12 PCR was then used as template in a nested-PCR
      using a specific Leishmania set S17/S18 as primers, to explain the amastigote
      forms. The nucleotide sequence of the new PCR product was identical to that of
      Leishmania (Leishmania) chagasi. This case, as far as we know, is the first
      report of a dog co-infected with these parasites, suggesting that besides L. (L.)
      chagasi, the natural transmission of T. (T.) evansi occurs in the area under
      study.

PMID- 16410963
TI  - Mycobacterium avium restriction fragment length polymorphism-IS IS1245 and the
      simple double repetitive element polymerase chain reaction typing method to
      screen genetic diversity in Brazilian strains.
AB  - Simple double repetitive element polymerase chain reaction (MaDRE-PCR) and Pvu II
      IS1245 restriction fragment length polymorphism (RFLP) typing methods were used
      to type 41 Mycobacterium avium isolates obtained from 14 AIDS inpatients and 10
      environment and animals specimens identified among 53 mycobacteria isolated from
      237 food, chicken, and pig. All environmental and animals strains showed orphan
      patterns by both methods. By MaDRE-PCR four patients, with multiple isolates,
      showed different patterns, suggesting polyclonal infection that was confirmed by
      RFLP in two of them. This first evaluation of MaDRE-PCR on Brazilian M. avium
      strains demonstrated that the method seems to be useful as simple and less
      expensive typing method for screening genetic diversity in M. avium strains on
      selected epidemiological studies, although with limitation on analysis identical
      patterns except for one band.

PMID- 16410964
TI  - Mycobacterium bovis identification by a molecular method from post-mortem
      inspected cattle obtained in abattoirs of Mato Grosso do Sul, Brazil.
AB  - The presence of Mycobacterium bovis in bovine carcasses with lesions suggestive
      of tuberculosis was evaluated. Seventy-two carcass samples were selected during
      slaughter inspection procedures in abattoirs in the state of Mato Grosso do Sul,
      Brazil. Seventeen (23.6%) of samples showed colonies suggestive of mycobacteria
      that were confirmed to be acid-fast bacilli by Ziehl-Neelsen staining. Polymerase
      chain reaction (PCR) using primers specific for M. bovis identified M. bovis in
      13 (76.5%) isolates. The PCR-restriction enzyme pattern analysis using gene
      encoding for the 65-kDa protein and two restriction enzymes identified the
      remaining four isolates that were represented by two M. tuberculosis complex and
      two nontuberculous mycobacteria. The results are indicative of infection of
      slaughter cattle by M. bovis and other mycobacteria in the state of Mato Grosso
      do Sul.

PMID- 16410965
TI  - Genetic diversity of Triatoma infestans (Hemiptera: Reduviidae) in Chuquisaca,
      Bolivia based on the mitochondrial cytochrome b gene.
AB  - Partial cytochrome b DNA sequences for 62 Triatoma infestans were analyzed to
      determine the degree of genetic variation present in populations of this insect
      in the northwest region of Chuquisaca, Bolivia. A total of seven haplotypes were
      detected in the localities sampled. The phylogenetic relationship and population
      genetic structure of the haplotypes found in this region, indicate that there is
      greater variation in this relatively small region of Bolivia than what has been
      previously reported by studies using the same gene fragment, for more distant
      geographic areas of this country. In addition, a comparison of rural and peri
      urban localities, indicate that there is no difference in the genetic variation
      of T. infestans between these two environments.

PMID- 16410966
TI  - A method for testing the host specificity of ectoparasites: give them the
      opportunity to choose.
AB  - Host-choice experiments were carried out with rodent and bat ectoparasites on
      Ilha Grande, state of Rio de Janeiro, Brazil. We constructed experimental
      chambers that enclosed three different rodent or bat host species, and then
      introduced a selected set of ectoparasitic arthropods. When given the opportunity
      to choose among host species, the ectoparasites showed a strong tendency to
      select their primary hosts, and reject novel host species. These kinds of simple
      experiments can be valuable tools for assessing the ability of ectoparasites to
      locate and discern differences between host species, and make choices about which
      hosts to infest, and which hosts to avoid.

PMID- 16410967
TI  - Development of enzyme-linked immunosorbent assays based on recombinant MSP1a and
      MSP2 of Anaplasma marginale.
AB  - Indirect enzyme-linked immunosorbent assays (ELISAs) based on recombinant MSP1a
      and MSP2 from a Brazilian isolate of Anaplasma marginale were developed to detect
      antibodies against this rickettsia in cattle. The high sensitivities (99% for
      both tests) and specificities (100% for both tests) were confirmed with sera from
      cattle positive or negative for A. marginale antibodies, respectively, by
      immunofluorescent antibody test. By the analysis of 583 sera from cattle of three
      regions of the state of Pernambuco, Brazil, the agreement between both tests was
      high, with a kappa index of 0.89. The similar performances of the ELISAs suggest
      that both tests can be used in epidemiological surveys for detection of
      antibodies to A. marginale in cattle.

PMID- 16410968
TI  - Efficacy of Citrus reticulata and Mirazid in treatment of Schistosoma mansoni.
AB  - This work has been carried out to investigate the effect of Schistosoma mansoni
      infection on mice livers after treatment with the ethanolic extract of Citrus
      reticulata root or the oleo-resin extract from Myrrh of Commiphora molmol tree
      (Mirazid), as a new antishistosomal drug. Marker enzymes for different cell
      organelles were measured; succinate dehydrogenase (SDH); lactate dehydrogenase
      (LDH) and its isoenzymes; glucose-6-phosphatase (G-6-Pase); acid phosphatase (AP)
      and 5'- nucleotidase. Liver function enzymes; aspartate aminotransferase (AST);
      alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were also
      estimated. Parasitological studies through ova count and worm burden will also be
      taken into consideration. The results showed a marked reduction in SDH, LDH, AST,
      and ALT enzyme activities and a significant increase in G-6-Pase, AP, 5'-
      nucleotidase, and ALP after S. mansoni infection. A noticeable alteration in LDH
      subunits were also noticed. Treatment with C. reticulata or Mirazid improved all
      the previous enzyme activities with a noticeable reduction in ova count and worm
      burden.

PMID- 16410969
TI  - Studies on antimicrobial activity, in vitro, of Physalis angulata L. (Solanaceae)
      fraction and physalin B bringing out the importance of assay determination.
AB  - Complex physalin metabolites present in the capsules of the fruit of Physalis
      angulata L. have been isolated and submitted to a series of assays of
      antimicrobial activity against Pseudomonas aeruginosa ATCC 27853, Staphylococcus
      aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538P, Neisseria
      gonorrhoeae ATCC 49226, Escherichia coli ATCC 8739; E. coli ATCC 25922, Candida
      albicans ATCC 10231 applying different methodologies such as: bioautography,
      dilution broth, dilution agar, and agar diffusion techniques. A mixture of
      physalins (pool) containing physalins B, D, F, G inhibit S. aureus ATCC 29213, S.
      aureus ATCC 25923, S. aureus ATCC 6538P, and N. gonorrhoeae ATCC 49226 at a
      concentration of 200 mg/microl, using agar dilution assays. The mixture was
      inactive against P. aeruginosa ATCC27853, E. coli ATCC 8739; E. coli ATCC 25922,
      C. albicans ATCC 10231 when applying bioautography assays. Physalin B (200
      microg/ml) by the agar diffusion assay inhibited S. aureus ATCC 6538P by +/- 85%;
      and may be considered responsible for the antimicrobial activity.

PMID- 16410970
TI  - Intracellular polyamine pools, oligopeptide-binding protein A expression, and
      resistance to aminoglycosides in Escherichia coli.
AB  - The role of intracellular free polyamine (putrescine and spermidine) pools in
      multiple resistance to aminoglycoside antibiotics was investigated among in vitro
      selected kanamycin-resistant Escherichia coli J53 mutants expressing diminished
      oligopeptide-binding protein (OppA) levels and/or defective ornithine
      decarboxylase (ODC) activity. The results suggest that diminished OppA content,
      but not defective ODC activity expression, increased the relative concentration
      of free spermidine as compared to the wild type strain. Moreover, by adding
      exogenous polyamines or polyamine synthesis inhibitors to cultures with different
      mutant strains, a direct relationship between the intracellular OppA levels and
      resistance to kanamycin was revealed. Collectively these results further suggest
      a complex relation among OppA expression, aminoglycoside resistance and polyamine
      metabolism.

PMID- 16410971
TI  - A new black fly isolate of Bacillus thuringiensis autoagglutinating strain highly
      toxic to Simulium pertinax (Kollar) (Diptera, Simuliidae) larvae.
AB  - Formulations containing the entomopathogenic Bacillus thuringiensis serovar
      israelensis strain IPS-82 has been widely applied for mosquito control around the
      world. Strain IPS-82 is highly active against Aedes aegypti but less active
      against other well-known vectors such as Culex quinquefasciatus and Simulium spp.
      larvae. Eighteen strains of B. thuringiensis were isolated from Simulium pertinax
      larvae naturally occurring in rivers of Southeast Brazil with one demonstrating
      special toxic effects. Simulated field tests against S. pertinax larvae showed
      that the native Brazilian autoagglutinating B. thuringiensis (LFB-FIOCRUZ 1035)
      has an LC50 at least 25 times lower than the standard IPS-82 strain. The same
      bacterial preparation was also tested against Ae. aegypti larvae in laboratory
      trials and the LC50 values obtained with LFB-FIOCRUZ 1035 were at least three
      times lower than the one for the IPS 82 strain. The results indicate that this
      strain is more toxic than the standard B. thuringiensis serovar israelensis (H14)
      in the two Dipteran species tested. It is noteworthy that differences between
      LC50 values were more pronounced in S. pertinax larvae, the source of the
      original isolation.

PMID- 16410972
TI  - Heme and innate immunity: new insights for an old molecule.
AB  - Hemolytic episodes such as sickle cell disease, malaria and ischemia-reperfusion
      occurrence are often associated to the statement of an inflammatory response
      which may develop or not to a chronic inflammatory status. Although these
      pathological states are triggered by distinct etiological agents, all of them are
      associated to high levels of free heme in circulation. In this review, we aim to
      focus the very recent achievements that have led to the statement of free heme as
      a proinflammatory molecule, which may play a central role during the onset and/or
      persistence of inflammation during these pathologies.

PMID- 16410973
TI  - The feature of papers and citation analysis of eleven journals in tropical
      medicine indexed by Science Citation Index Expanded.
AB  - To determine the features of papers, authors, and citation of eleven journals in
      tropical medicine indexed by Science Citation Index Expanded, the database of the
      Institute for Scientific Information, we analyzed original articles, editorials,
      reviews, corrections, letters, biographies, and news published in these journals.
      The results show that these journals covered 107 countries or regions on six
      continents. The average number of reference was 23.05, with 87.89% of the
      references from periodicals. The Price Index was 31.43% and the self-citing rate
      was 7.02%. The references in the first 20 journals ranked by the amount of
      citation accounted for 36.71% of the total citations. Brazil, United States,
      India, and England are more advanced in tropical medicine research. The
      conclusion is that these journals covered most research done in these countries
      or regions. Most researches were done by cooperation of the researchers, but many
      of the publications used outdated articles and should include newer information.

PMID- 16410975
TI  - [History of public health in the S. Paulo State, Brazil. 1973].

PMID- 16410976
TI  - [Public health in Sao Paulo: history and characters].

PMID- 16410977
TI  - [Rodolfo Mascarenhas and public health history in Sao Paulo].

PMID- 16410978
TI  - [Situation of the Public Health medical care at the "Great Sao Paulo"
      Metropolitan Area, Brazil. 1971].

PMID- 16410979
TI  - [Health reform in Sao Paulo during the 70's and the Unified Health System (SUS)].

PMID- 16410980
TI  - [Reform on medical care assistance in Great Sao Paulo in the 70's].

PMID- 16410981
TI  - Methodological aspects of the 1993 Pelotas (Brazil) Birth Cohort Study.
AB  - This paper describes the main methodological aspects of a cohort study, with
      emphasis on its recent phases, which may be relevant to investigators planning to
      carry out similar studies. In 1993, a population based study was launched in
      Pelotas, Southern Brazil. All 5,249 newborns delivered in the city's hospitals
      were enrolled, and sub-samples were visited at the ages of one, three and six
      months and of one and four years. In 2004-5 it was possible to trace 87.5% of the
      cohort at the age of 10-12 years. Sub-studies are addressing issues related to
      oral health, psychological development and mental health, body composition, and
      ethnography. Birth cohort studies are essential for investigating the early
      determinants of adult disease and nutritional status, yet few such studies are
      available from low and middle-income countries where these determinants may
      differ from those documented in more developed settings.

PMID- 16410982
TI  - [Population study of premenstrual syndrome].
AB  - OBJECTIVE: To study the prevalence of premenstrual syndrome and the factors
      associated with this, by comparing the obtained frequency with the self-reported
      frequency. METHODS: This was a cross-sectional population-based study, involving
      1,395 women aged 15 to 49 years old in a medium-sized municipality in Southern
      Brazil, carried out in 2003. Questionnaires were applied to measure the
      prevalence of premenstrual syndrome by means of a score based on five
      premenstrual symptoms that interfered with family life or led to absence from
      work or school. Associations with socioeconomic, demographic and behavioral
      variables were investigated. Self-reported syndrome was investigated with regard
      to its sensitivity and specificity, taking the score as the gold standard. The
      statistical analyses performed were Pearson chi2, Mantel-Haenszel and Poisson
      regression, with Kappa coefficients to verify the concordance of the responses.
      RESULTS: The obtained prevalence was 25.2% (95% CI: 22.5-27.9) and the self
      reported prevalence was 60.3% (95% CI: 57.4-63.3). The principal premenstrual
      symptoms found were: irritability, abdominal discomfort, nervousness, headache,
      fatigue and breast pain; all of these showed prevalence of over 50%. Higher risk
      was presented by women of higher socioeconomic level, better schooling level,
      aged under 30 years and with white skin color. Psychotropic drug users and women
      who were not using any hormonal contraceptive presented higher prevalence of the
      syndrome. The sensitivity of the test was 94%, specificity 51% and accuracy 62%.
      CONCLUSIONS: A high prevalence of premenstrual syndrome was found. Even though
      the women's perception of the syndrome was higher than the result measured by the
      symptom score, one quarter of the women presented this health problem.

PMID- 16410983
TI  - [Knowledge of contraceptive methods among adolescent students].
AB  - OBJECTIVE: To compare the knowledge of contraceptive methods as well as to
      identify factors associated with adequate knowledge among public and private
      school adolescents. METHODS: A cross-sectional study comprising 1,594 adolescents
      aged between 12 and 19 years old from 13 public and five private schools in the
      city of Sao Paulo city, Brazil, was carried out from June to December 2003.
      Schools were randomly selected and students filled out a questionnaire about
      sociodemographic, reproductive and contraceptive methods. The prevalence ratios
      were estimated with a 95% confidence interval for each question on their
      knowledge of contraceptive methods and by school group. Each question correctly
      answered received a half score, and the cut-off value was 50% of correct answers.
      Statistical tests utilized were Chi-square and Wilcoxon-Gehan tests and Poisson
      multiple regression model. RESULTS: Of all respondents, 61% were of females in
      both school groups. Most students had low socioeconomic condition in public
      schools while they had mostly high socioeconomic condition in private schools
      (p<0.001). Nearly 18.6% private and 28.6% public school students were sexually
      active (p<0.002). In regard to their knowledge, 25.7% of public and 40.8% of
      private school students had a score equal to or above five. Factors associated
      with higher knowledge were: being female, at high school of a private school,
      having high socioeconomic condition, having had sexual intercourse and being
      older. CONCLUSIONS: Knowledge of contraceptive methods was low in both public and
      private school students. The study results show that both underprivileged as well
      as high socioeconomic adolescents need to have adequate information about family
      planning to improve their knowledge and change their behavior.

PMID- 16410984
TI  - [Prevalence of postpartum depression and associated factors].
AB  - OBJECTIVE: To assess the prevalence of postpartum depression and associated
      factors. METHODS: The study was carried out in Pelotas, a city in the Southern
      region of Brazil, between October and November 2000. Mothers (n=410) were
      interviewed in the hospital using two questionnaires on obstetric and
      psychosocial data. Later, these mothers were visited at home, within 30 to 45
      days after delivery. Occurrence of postpartum depressive symptoms was assessed by
      the Hamilton Scale for Depression. Chi-square test was used for comparison
      between proportions and non conditional logistic regression was utilized in the
      multivariate analysis. Data analysis was conducted hierarchically: economic
      variables in the first level, sociodemographic in the second level, the
      obstetrics variables in the third level and, in the fourth level, the
      psychosocial variables. RESULTS: The prevalence of postpartum depression observed
      in this sample was 19.1%. Family income (OR=5.24; CI 95%: 2.00-13.69), preference
      as to the child's gender (boys: OR=3.49; CI 95%: 1.76-6.93) and thinking about
      interrupting the pregnancy (OR=2.52; CI 95%: 1.33-4.76), were variables
      associated with postpartum depression. CONCLUSIONS: These results indicate that
      low economic status of the puerperal woman and nonacceptance of pregnancy are key
      elements in the development of postpartum depression.

PMID- 16410985
TI  - Lead, hemoglobin, zinc protoporphyrin and ferritin concentrations in children.
AB  - OBJECTIVE: To assess the relationship of blood lead and hemoglobin, zinc
      protoporphyrin, and ferritin concentrations in children. METHODS: A cross
      sectional study was carried out in 136 anemic and non-anemic children from two
      rural villages near a lead smelter in Adrianopolis, Southern Brazil, from July to
      September 2001. Hemoglobin electrophoresis was performed to exclude children with
      hemoglobin variants and thalassemia syndromes associated with anemia. Lead was
      determined by atomic absorption spectrophotometry; hemoglobin by automated cell
      counting; zinc protoporphyrin by hematofluorometry; ferritin by
      chemiluminescence. Student's t-test, Mann-Whitney test, and the c(2) test were
      used to assess the significance of the differences between the variables
      investigated in anemic and non-anemic children. Stepwise multivariate linear
      regression analysis was performed using two models for anemic and non-anemic
      children respectively. RESULTS: Lead was negatively associated to hemoglobin
      (p<0.017) in the first model, and in the second model lead was positively
      associated to zinc protoporphyrin (p<0.004) after controlling for ferritin, age,
      sex, and per capita income. There was an inverse association between hemoglobin
      and blood lead in anemic children. It was not possible to confirm if anemic
      children had iron deficiency anemia or subclinical infection, considering that
      the majority (90.4%) had normal ferritin. CONCLUSIONS: The study detected a
      relationship between anemia and elevated blood lead concentrations. Further
      epidemiological studies are necessary to investigate the impact of iron
      nutritional interventions as an attempt to decrease blood lead in children.

PMID- 16410986
TI  - [Effects of air pollution on children's health in a city in Southeastern Brazil].
AB  - OBJECTIVE: Of the effects of air pollution on children's health, increased
      pneumonia admission rate is one of the most important. The study aimed at
      estimating the association between pneumonia admissions and increased air
      pollutants. METHODS: An ecological time-series study was carried out in the
      municipality of Sao Jose dos Campos, Southeastern Brazil, in the years 2000 and
      2001. Daily records of pneumonia admissions, air pollutants (SO2, O3, and PM10)
      and weather conditions (temperature and humidity) were analyzed. The correlations
      between the study variables were estimated using Pearson's correlation. The
      associations between pneumonia and air pollutants were estimated using
      generalized additive Poisson regression models. The percentage increase (and
      their respective 95% CI) in pneumonia admission rate was estimated for the
      interquartile range of each air pollutant studied. RESULTS: The three pollutants
      analyzed presented lagged effects on pneumonia admission rate, beginning at lag 3
      or 4 and lasting for no more than two days. The 8-day cumulative effect estimate
      showed that an increase of 24.7 mg/m3 in PM10 concentration increased pneumonia
      admission rate in 9.8%. CONCLUSIONS: The study corroborates that adverse health
      effects of air pollutants can be observed even in medium-sized cities. The
      magnitude of the effect was similar to that found in the city of Sao Paulo.
      Moreover, children are highly susceptible to air pollution exposure.

PMID- 16410987
TI  - [Silica exposure index in gold mining].
AB  - OBJECTIVE: To develop a cumulative silica exposure index, including time period,
      duration and intensity of exposure, and to test this index as for occurrence and
      severity of silicosis. METHODS: A cross-sectional study was carried out
      comprising 140 former gold miners from two localities in Southeastern Brazil
      between November 1997 and December 1999. Complete data on occupational and
      medical histories, chest x-rays and spirometry were analyzed. Borderline cases on
      the x-rays were also submitted to high-resolution chest computed tomography. The
      exposure index was the sum of scores obtained by logarithmic transformation of
      respirable silica concentration related to job tasks, mines and work time.
      Parametric tests were used for comparing averages between the groups of interest.
      RESULTS: The silica exposure index was able to discriminate the main outcome
      (silicosis) as well as other outcomes (tuberculosis and lung emphysema) in the
      whole group at p-values of 0.008, 0.016 and <0.001 respectively. In regard to the
      four main categories of silicosis, the Tukey test showed differences in the
      averages of the exposure index in the categories 0 and 3 and 1 and 3. However, in
      the borderline cases subgroup, the exposure index was not satisfactory for cases
      submitted to x-rays and tomography and it could not differentiate other outcomes.
      CONCLUSIONS: The silica exposure index represents an advance in exposure
      evaluation of former miners. However, other information, such as clinical and
      lung functional data are needed for better understanding disease progress in
      silica exposed cases, especially among borderline cases.

PMID- 16410988
TI  - [Liver enzyme abnormalities among oil refinery workers].
AB  - OBJECTIVE: Occupational exposure typical of an oil refinery may alter liver
      function among the workers. Thus, the objective of the study was to identify risk
      factors for liver enzyme abnormalities among oil refinery workers. METHODS: The
      workers at an oil refinery in Northeastern Brazil underwent routine annual
      medical examination from 1982 to 1998. This case-control study investigated all
      the 150 cases of individuals with simultaneous gamma-glutamyltransferase and
      alanine aminotransferase abnormalities of at least 10% above reference levels. As
      controls, 150 workers without any liver enzyme or bilirubin abnormalities since
      starting to work there were selected. Odds ratios and the respective 95%
      confidence intervals were calculated from logistic regression models. RESULTS: In
      all the production sectors, the risk of liver enzyme abnormalities was
      significantly higher than in the administrative sector (OR=5.7; 95% CI: 1.7
      18.4), even when the effects of alcohol, obesity and medical history of hepatitis
      were controlled for. During the period from 1992 to 1994, 88 out of the 89 cases
      occurred among workers from the various production sectors. CONCLUSIONS:
      Occupational exposure plays an important role in causing liver enzyme
      abnormalities among oil refinery workers. This is in addition to the specifically
      biological and/or behavioral risk factors such as obesity and alcohol
      consumption.

PMID- 16410989
TI  - [The individual's status in the labor market and health inequity in Brazil].
AB  - OBJECTIVE: To investigate inequalities in personal health conditions and in the
      utilization of healthcare services according in relation to the individual's
      status in the labor market. METHODS: This study was based on 39,925 males aged 15
      to 64 years living in 10 Brazilian metropolitan regions, who took part in the
      1998 National Household Survey. They were classified as formal labor, informal
      labor, unemployed or outside of the labor market. Each category was compared with
      formal labor regarding sociodemographic characteristics, health status indicators
      and healthcare utilization. This analysis was by means of Pearson's Chi-square
      test. Multinomial logistic regression was used to investigate independent
      associations between labor market status, health status indicators and healthcare
      utilization. RESULTS: The classification of the participants' status was that
      52.2% were formal labor, 27.7% informal labor, 10% unemployed and 10.2% were
      outside of the labor market. There were significant differences between these
      categories with respect to age, schooling, household income, household status and
      region of residence. Independent of the sociodemographic characteristics,
      unemployment, informal labor status and, especially, exclusion from the labor
      market remained associated with poor health status. CONCLUSIONS: The individual's
      status in the labor market is expressed through a gradient of inequality in
      health conditions. These findings reinforce the need to also consider the
      individual's status in the labor market in studies on healthcare inequalities.

PMID- 16410990
TI  - [Modifications in psychotropic drug use patterns in a Southern Brazilian city].
AB  - OBJECTIVE: To assess the prevalence and patterns of psychotropic use by
      population and to compare the results with a study carried out in 1994. METHODS:
      This is a population-based cross-sectional study carried out in 2003 with 3,542
      participants aged 15 or older who lived in an urban area in Southern Brazil. Two
      week recall data were collected in household interviews through the same
      questionnaire used in the 1994 study. The variables studied were age, gender,
      race, education, family income, marital status, smoking, medical diagnosis of
      hypertension, and physician visit at last three months. Pearson's Chi-square and
      linear tendency were used in the bivariate analysis. Four levels of multivariate
      analysis was performed. RESULTS: The overall prevalence of psychotropic use was
      9.9% (CI 95%: 8.9-10.9). There was no significant difference among standardized
      age groups when compared to the prevalence rates observed in 1994. Higher
      psychotropic use was associated with being female, older age, medical diagnosis
      of hypertension, and health service utilization. Of those interviewed, 74% of
      those drug users were using psychotropic drugs for over three months.
      CONCLUSIONS: A decade later, prevalence remained high, yet psychotropic drug use
      did not increase. The association between health service utilization and
      consumption shows the importance of the appropriate prescription of psychotropic
      drugs and regular follow-up of those prescribed them by physicians.

PMID- 16410991
TI  - [Factors associated with influenza vaccination among elderly persons in
      Southeastern Brazil].
AB  - OBJECTIVE: Even though influenza vaccination is free and widely available in
      Brazil since 1999, coverage is still inadequate in several of the country's
      municipalities. The aim of the present study was to estimate vaccine coverage and
      to identify factors related to vaccination against influenza in the elderly
      population. METHODS: A household survey was carried out using a systematic random
      sample (N=365) of the urban population older than 60 years from the city of
      Botucatu, Southeastern Brazil. A logistic regression model using vaccination in
      2002 as the dependent variable was used. The following covariables were tested:
      sex, age, socioeconomic variables (per capita income, number of persons per
      dormitory, schooling, marital status, occupation, time living in the city),
      history of morbidity and hospital admission, smoking, respiratory symptoms in
      last 15 days, and community activities (voluntary work, neighborhood and church
      activities). RESULTS: Vaccine coverage was 63.2% (95% CI: 58.3-68.2). We found a
      lower proportion of vaccination among the 60-64 years age group. Variables
      associated with vaccination in the final model were age (OR=1.09 per year; 95%
      CI: 1.06-1.13); arterial hypertension (OR=1.92; 95% CI: 1.18-3.13); and
      participation in community activities (OR=1.63; 95% CI: 1.01-2.65). With the
      exception of hypertension, vaccination among subjects with chronic diseases did
      not reach adequate levels, as expected for this high-risk group. Participation in
      social and community activities was associated with vaccination status.
      CONCLUSIONS: Socioeconomic conditions, habits, and age did not restrict access to
      vaccination campaigns. On the other hand, specific campaigns aimed at the 60-64
      years age group may increase vaccination coverage.

PMID- 16410992
TI  - [Prevalence of Cryptosporidium sp. in institutionalized dogs in the city of Sao
      Paulo, Brazil].
AB  - OBJECTIVE: Dogs play an important role as infection source of human
      cryptosporidiosis. The objective of the study was to determine the prevalence of
      Cryptosporidium sp. in dogs as well as to compare two techniques of fecal
      analysis. METHODS: Four-hundred and fifty canine fecal samples from the city of
      Sao Paulo were analyzed between 2003 and 2004. Fecal samples were randomly
      selected from dogs housed in a university veterinary hospital (group 1, n=200)
      and private kennels (group 2, n=250). The detection of Cryptosporidium was
      performed using modified Ziehl-Neelsen staining and Polymerase Chain Reaction
      (PCR) technique. Statistical analysis was performed using the two-tailed test of
      significance at 5% confidence interval (z critical=+/-1.645). RESULTS: Only
      Cryptosporidium parvum oocysts were found. The prevalences found by light
      microscopy examination and PCR techniques were 8.8% and 9.5%, respectively. Young
      animals showed a lower frequency (5.5%) compared to adults (10.1%). There was no
      statistically significant difference in Cryptosporidium prevalence between males
      and females. CONCLUSIONS: The prevalence of C. parvum in the canine population
      studied was similar to that one found in the literature and affects equally males
      and females. The use of PCR allowed the detection of more positive cases than
      light microscopy.

PMID- 16410993
TI  - [Cultural conceptions on dengue in urban contexts in Mexico].
AB  - OBJECTIVE: To explore the conceptual dimensions of dengue in the urban context,
      aiming at creating hypotheses about community attitudes toward prevention
      campaigns. METHODS: An exploratory cross-sectional study was carried out between
      March and April 2003 comprising 130 people selected by proposition sampling in
      three municipalities with different dengue prevalences in Mexico. Semi-structured
      interviews were applied using free lists, pile sorts and triads. Dengue-related
      terms and groups of conceptual dimensions were investigated. A consensual
      analysis was performed by factorizing the major components as well as a
      dimensional analysis with hierarchical clustering and multidimensional scales.
      RESULTS: The consensual model showed high homogeneity in dengue conceptions
      (values of 14.5 and 13.5 in the most prevalent contexts, and 5.4 in the least
      prevalent one). The common dimensions of conceptions were: preventive measures,
      symptoms, causes and reservoirs of Aedes aegypti (goodness of fit test values:
      <0.28). In the three contexts studied, a conception of basic prevention based on
      public actions by health officials predominated while individual and community
      actions were almost never mentioned. A moral dimension also appeared in the
      conception based on a notion of hygiene as a differentiating mechanism between
      the nearby community (clean) and outside people and communities (dirty and sick).
      CONCLUSIONS: The cultural conceptions of dengue do not favor self-managed
      community involvement in vertical prevention campaigns, and create obstacles to
      modifying community and individual prevention and control practices.

PMID- 16410994
TI  - [Data quality of dengue epidemiological surveillance in Belo Horizonte,
      Southeastern Brazil].
AB  - OBJECTIVE: To evaluate the quality of data from the Brazilian information system
      for mandatory reporting diseases, for the detection of cases notified as
      suspected dengue fever and hospitalized in the public and private hospitals
      associated to the Public Health System. METHODS: The study was carried out in
      Belo Horizonte, Southeastern Brazil, during the years of 1996 to June 2002. The
      criterion of evaluation used were those recommended by the Guidelines for
      Evaluating Public Health Surveillance Systems. As a reference standard, medical
      charts recorded in the Unified System hospitalized discharge database system were
      revised and validated. A total of 266 (90%) of 294 medical charts were selected;
      230 (86.5%) filled the suspect dengue fever criterion. To verify possible
      association between underreporting and selected variables, was used the odds
      ratio, with 95% of confidence interval in a logistic regression model. The
      sensitivity was defined as the proportion of hospitalized dengue cases registered
      in both systems. Predictive value positive was calculated as the proportion of
      confirmed cases and those recorded in the reporting system. RESULTS:
      Underreporting of suspected dengue fever was of 37% cases during 1997 to 2002, it
      was five times higher during the first three years (OR=5.93; 95% CI: 2.50-14.04)
      and eight times higher for patients hospitalized in private hospitals than in the
      public ones (OR=8.42; 95% CI: 2.26-31.27). Underreport was also associated to
      cases with no haemorrhagic episodes (OR=2.81; 95% CI: 1.28-6.15) and without
      dengue-specific laboratory exams in medical charts (OR=4.07; 95% CI:1.00-16.52).
      Sensitivity was 63% and predictive value positive was 43%. CONCLUSIONS: Cases
      recorded in the reporting system were those more severe and did not represent the
      total of cases hospitalized in Unified Health System, thus the case fatality rate
      may be overestimated. The results indicate the necessity of changes in the
      evaluated surveillance model and in the implementation of the qualification of
      the health professionals, mainly those working in the private hospitals
      associated to Unified Health System.

PMID- 16410996
TI  - Effects of health decentralization, financing and governance in Mexico.
AB  - OBJECTIVE: To identify the effects of decentralization on health financing and
      governance policies in Mexico from the perspective of users and providers.
      METHODS: A cross-sectional study was carried out in four states that were
      selected according to geopolitical and administrative criteria. Four indicators
      were assessed: changes and effects on governance, financing sources and funds,
      the final destination of resources, and fund allocation mechanisms. Data
      collection was performed using in-depth interviews with health system key
      personnel and community leaders, consensus techniques and document analyses. The
      interviews were transcribed and analyzed by thematic segmentation. RESULTS: The
      results show different effectiveness levels for the four states regarding changes
      in financing policies and community participation. Effects on health financing
      after decentralization were identified in each state, including: greater
      participation of municipal and state governments in health expenditure, increased
      financial participation of households, greater community participation in low
      income states, duality and confusion in the new mechanisms for coordination among
      the three government levels, absence of an accountability system, lack of human
      resources and technical skills to implement, monitor and evaluate changes in
      financing. CONCLUSIONS: In general, positive and negative effects of
      decentralization on health financing and governance were identified. The effects
      mentioned by health service providers and users were related to a diversification
      of financing sources, a greater margin for decisions around the use and final
      destination of financial resources and normative development for the use of
      resources. At the community level, direct financial contributions were mentioned,
      as well as in-kind contributions, particularly in the form of community work.

PMID- 16410995
TI  - [Evaluation of the organizational structure of HIV/AIDS outpatient care in
      Brazil].
AB  - OBJECTIVE: In the context of universal access to antiretroviral treatment, the
      results of the Brazilian AIDS Program will depend on the quality of the care
      provided. The aim of the present study was to evaluate the healthcare provided by
      outpatient services for the treatment of AIDS patients. METHODS: The present
      study was carried out in seven Brazilian States between 2001 and 2002. We
      evaluated the quality of the care provided to AIDS patients from the standpoint
      of resource availability and care process organization. A questionnaire
      comprising 112 structured questions addressing these aspects was sent to 336
      services. RESULTS: Response rate was 95.8% (322). Greater adequacy is seen for
      indicators of resource availability than for those of work organization. The
      supply of antiretroviral medication is sufficient in 95.5% of services. CD4 and
      viral load tests are available at adequate amounts in 59 and 41% of services,
      respectively. In 90.4% of services there is at least one non-medical professional
      (psychologist, nurse, or social worker). As to work organization, 80% scheduled
      the date but not the time of medical appointments; 40.4% scheduled more than 10
      appointments per period; 17% did not have exclusive managers; and 68.6% did not
      hold systematic staff meetings. CONCLUSIONS: The results indicate that, in
      addition to ensuring the more homogeneous distribution of resources, the program
      must invest in the training and dissemination of care management skills, as
      confirmed by the results of care process organization.

PMID- 16410997
TI  - Mental health research in Brazil: policies, infrastructure, financing and human
      resources.
AB  - The objective of this descriptive study was to map mental health research in
      Brazil, providing an overview of infrastructure, financing and policies mental
      health research. As part of the Atlas-Research Project, a WHO initiative to map
      mental health research in selected low and middle-income countries, this study
      was carried out between 1998 and 2002. Data collection strategies included
      evaluation of governmental documents and sites and questionnaires sent to key
      professionals for providing information about the Brazilian mental health
      research infrastructure. In the year 2002, the total budget for Health Research
      was USD 101 million, of which USD 3.4 million (3.4) was available for Mental
      Health Research. The main funding sources for mental health research were found
      to be the Sao Paulo State Funding Agency (FAPESP, 53.2%) and the Ministry of
      Education (CAPES, 30.2%). The rate of doctors is 1.7 per 1,000 inhabitants, and
      the rate of psychiatrists is 2.7 per 100,000 inhabitants estimated 2000 census.
      In 2002, there were 53 postgraduate courses directed to mental health training in
      Brazil (43 in psychology, six in psychiatry, three in psychobiology and one in
      psychiatric nursing), with 1,775 students being trained in Brazil and 67
      overseas. There were nine programs including psychiatry, neuropsychiatry,
      psychobiology and mental health, seven of them implemented in Southern states.
      During the five-year period, 186 students got a doctoral degree (37 per year) and
      637 articles were published in Institute for Scientific Information (ISI)-indexed
      journals. The investment channeled towards postgraduate and human resource
      education programs, by means of grants and other forms of research support, has
      secured the country a modest but continuous insertion in the international
      knowledge production in the mental health area.

PMID- 16410998
TI  - [Environmental surveillance in health in Brazil's Unified Health System].
AB  - The incorporation of environmental surveillance in the field of public health
      policies is a relatively recent demand in Brazil. One of the major challenges in
      environmental health surveillance is defining its object and the specificity of
      its practice. The expanded concept of exposure, treated as a set of complex
      relations between a society and the environment, and not as a personal attribute,
      is central to the definition of indicators and should guide the practice of
      environmental surveillance in the health sector. Among the difficulties
      encountered in applying this concept within the Brazilian Health System, is the
      need to restructure health surveillance activities and to form multidisciplinary
      teams capable of dialoguing with other sectors. Furthermore, information systems
      capable of aiding in health situation analysis and decision making must be
      constructed. Taking this into consideration, a review of the object and concepts
      of environmental health surveillance was undertaken and the challenges with
      respect to its implementation in the Brazilian Health System were identified.

PMID- 16410999
TI  - [Notion of meaning in health qualitative research: the Anthropology
      contribution].

PMID- 16411000
TI  - Low birth weight and periodontal diseases association.

PMID- 16411001
TI  - [Avian influenza and human cases].

PMID- 16411002
TI  - [Partnerships to reduce drug misuse].

PMID- 16411003
TI  - [Piracy: what you pay is what you get].

PMID- 16411005
TI  - The importance of empirical research in bioethics: the case of human embryo stem
      cell research.

PMID- 16411006
TI  - Maternity care by family physicians: characteristics of successful and
      sustainable models.

PMID- 16411007
TI  - Letter from Australia.

PMID- 16411008
TI  - Pregnancy outcomes of First Nations women in relation to pregravid weight and
      pregnancy weight gain.
AB  - OBJECTIVE: To determine the effect of pregravid weight and pregnancy weight gain
      on pregnancy outcomes in Cree women. METHODS: We reviewed maternal and infant
      outcomes of the first pregnancy in Cree women living in James Bay, Quebec, from
      1994 to 2000. We examined data from women who had a full-term singleton birth and
      a maternal pregravid body mass index (BMI) > or = 18.5 kg/m2 and whose weight had
      been recorded in the first trimester and within one month prior to delivery.
      Weight in the first trimester was used to estimate pregravid BMI. RESULTS: Data
      were available for 603 women. At the beginning of pregnancy, 23.1% of the women
      had normal weight (BMI 18.5-24.9 kg/m2), 27.9% were overweight (BMI 25-29.9
      kg/m2), and 49.1% were obese (BMI > or = 30 kg/m2). Nearly one-half of the women
      gained excessive weight in pregnancy. Adverse outcomes were less common in women
      with a normal pregravid BMI than in women with a pregravid BMI in the overweight
      or obese range. Obese women with excessive weight gain had a higher prevalence of
      preeclampsia (14.9%) than obese women with low (3.7%) or acceptable (6.3%) weight
      gain; however, obese women with excessive weight gain had a lower prevalence of
      gestational diabetes mellitus. CONCLUSION: Interventions must be developed to
      prevent pregravid obesity and excessive weight gain in pregnancy in Cree women to
      improve maternal and fetal outcomes.

PMID- 16411009
TI  - The use of an ultrasound bladder scanning device in women undergoing
      urogynaecologic surgery.
AB  - OBJECTIVE: To compare the accuracy of using a bladder scanner to measure post
      voiding residual urine volume with measurement by intermittent catheterization in
      a postoperative urogynaecology population. METHODS: Prior to implementation of
      the study, nurses were trained in the use of a bladder ultrasound scanner. Post
      void residual urine volume in postoperative patients was assessed by a nurse with
      the scanner; a second nurse, blinded to the scanner result, then catheterized the
      patient's bladder. Each patient rated the pain experienced with bladder scanning
      and with catheterization. A prospective comparison of the volumes assessed by
      ultrasound and measured by catheterization used 127 pairs of data; each woman
      served as her own control. The correlation of urine volumes was determined, and
      the difference in pain score was calculated using the Student t test. RESULTS:
      The mean age of patients was 56.5 years (range 40-79). All four bladder quadrants
      were visualized in 34.4% of scans. The correlation coefficient for volumes
      measured by scanning and catheterization was 0.70 (P < 0.001; range -349 mL to
      +692 mL). Consistently, using the scanner resulted in underestimation of the
      urine volume. The sensitivity of the bladder scanner (0.58 for residual volumes >
      200 mL) therefore makes it a poor tool for assessing postoperative urinary
      retention in women undergoing urogynaecologic surgery. Pain scores recorded with
      catheterization (2.9/10) were significantly less than those recorded with bladder
      scanning (4.2/10) (P < 0.001). CONCLUSIONS: Bladder scanning by staff nurses had
      limited value in assessing postoperative residual urine volumes. The accuracy of
      assessment might increase with greater experience with the procedure. The greater
      discomfort reported by patients with use of the scanner supports continued use of
      catheterization to assess residual urine volume.

PMID- 16411010
TI  - Eligibility of cryopreserved human embryos for stem cell research in Canada.
AB  - OBJECTIVE: To determine whether cryopreserved embryos in Canadian in vitro
      fertilization (IVF) clinics available (in theory) for research use are actually
      eligible (in practice) for stem cell research in accordance with the Assisted
      Human Reproduction Act, the Canadian Institutes of Health Research's Human
      Pluripotent Stem Cell Research: Guidelines for CIHR-Funded Research, and the Tri
      Council Policy Statement: Ethical Conduct for Research Involving Humans. METHODS:
      Copies of current and past patient information sheets and consent forms for
      embryo cryopreservation, the future disposition of cryopreserved embryos, and the
      donation of cryopreserved embryos for research were requested from Canadian IVF
      clinics. Fourteen of 24 clinics (response rate 58%) provided one or more of the
      requested documents. RESULTS: A review of the documents currently in use showed
      that, as of May 2005, all 14 responding clinics require an advance directive for
      the eventual disposition of cryopreserved embryos. Ten of these 14 clinics allow
      the donation of cryopreserved embryos for research. Only three of these 10
      clinics, however, satisfy in writing the disclosure requirements for embryo
      research at the time of initial consent for the cryopreservation and future
      disposition of embryos. Only one clinic specifically identifies the option of
      embryonic stem cell research. CONCLUSION: Only three of the responding Canadian
      IVF clinics provide written details about future donation of cryopreserved
      embryos for research use and about the need for re-contact in accordance with
      relevant legislation and guidelines. Two of these three clinics, however, include
      disposition options that may not be legally available. In the event of death or
      loss of contact, it will not be possible to get project-specific research consent
      from the legitimate embryo providers as required by law. These same two clinics
      also fail to mention embryonic stem cell research as one of the research
      categories. It follows that we have identified only one Canadian IVF clinic with
      cryopreserved embryos unequivocally eligible for stem cell research, provided the
      forms we reviewed were used to obtain consent for the cryopreservation of those
      embryos.

PMID- 16411011
TI  - Maternal transport policy.

PMID- 16411012
TI  - Choice of surgery for stress incontinence.
AB  - OBJECTIVE: To outline the evidence for the efficacy of surgical procedures used
      for the primary treatment of urinary incontinence. OPTIONS: The range of surgical
      options available for the primary treatment of urinary incontinence in women.
      OUTCOMES: The best possible outcomes for women undergoing primary surgery for
      urinary incontinence. To provide a current understanding of the evidence
      available as the basis of an informed discussion of the anticipated outcome of
      surgery. EVIDENCE: A systematic review of clinical trials of the outcomes of
      primary surgical treatment of urinary incontinence. VALUES: The quality of the
      evidence is rated using the criteria described by the Canadian Task Force on
      periodic health examination (Table). BENEFITS, HARMS, AND COSTS: Careful
      consideration of the surgical options available will result in informed choice,
      which is essential to the process of determining the most appropriate surgery for
      a woman. Use of a range of surgeries that have the highest proven efficacy is
      most likely to result in long-term patient satisfaction.

PMID- 16411013
TI  - Prognostic significance of extrathyroid extension of papillary thyroid carcinoma:
      massive but not minimal extension affects the relapse-free survival.
AB  - OBJECTIVES: Extrathyroid extension has been recognized as a prognostic factor in
      papillary thyroid carcinoma. In the most recent version of the UICC TNM
      classification system, extrathyroid extension has been classified into two
      grades, minimal extension (extension to sternothyroid muscle or perithyroid soft
      tissues) and massive extension (extension to subcutaneous soft tissue, larynx,
      trachea, esophagus, or recurrent laryngeal nerve). In this study, we investigated
      the prognostic significance of each of the two types of extension. PATIENTS AND
      METHODS: One thousand and sixty-seven patients with papillary thyroid carcinoma
      without distant metastasis at surgery, who underwent surgical treatment in Kuma
      hospital between 1990 and 1995 and had been followed postoperatively for 60
      months or more, were enrolled in this study. The grading of extrathyroid
      extension was based on both pathological findings and intraoperative surgical
      findings. RESULTS: In univariate analysis, although patients with massive
      extension showed a significantly worse relapse-free survival (RFS) rate than
      those with no or minimal extension (P < 0.0001), there was no difference in the
      RFS rate between patients with no extension and those with minimal extension.
      Among patients with massive extension, the RFS rate tended to be worse in those
      with posterior extension than in those with anterior extension (P = 0.0562).
      Furthermore, the RFS rate of patients with massive posterior extension only to
      the recurrent nerve demonstrated a better RFS rate than those with extension to
      other posterior organs (P = 0.0052). Multivariate analysis demonstrated that
      massive extrathyroid extension is recognized as an independent prognostic factor
      for RFS (P = 0.0003). CONCLUSIONS: These findings suggest that (1) upgrading of T
      category for tumors with massive extension is appropriate, whereas that for
      tumors with only minimal extension is not, and (2) careful surgical treatment and
      postoperative follow-up are required for tumors with massive extension to
      posterior organs other than the recurrent laryngeal nerve.

PMID- 16411014
TI  - Usefulness of multidetector computed tomography for the initial assessment of
      blunt abdominal trauma patients.
AB  - BACKGROUND: The prompt detection and accurate localization of abdominal injuries
      are difficult. Some diagnostic modalities, including laboratory tests,
      ultrasound, and diagnostic peritoneal lavage (DPL) were used to evaluate patients
      with blunt abdominal trauma, with various advantages and pitfalls. We aimed to
      evaluate the risk and benefit of using multidetector computed tomography (MDCT)
      as an initial assessment tool for proper diagnosis and treatment planning of
      patients with blunt abdominal trauma. METHODS: Two hundred fifty-two patients
      with blunt abdominal trauma were prospectively enrolled. Multidetector computed
      tomography was performed during resuscitation. The risk and benefit of using MDCT
      in the diagnosis and planning of treatment were analyzed. RESULTS: The time
      required for a MDCT examination averaged 10.2 minutes. Of the studies done, 224
      revealed abdominal injuries. Of those, 34 were performed in patients with
      unstable hemodynamic status without adverse effect. Prompt diagnosis and proper
      treatment were given according to the MDCT findings. A total of 43 (17.1%) MDCTs
      showed contrast extravasation. Active bleeding was confirmed in all and treated
      with transarterial embolization (30) or surgery (13). Another 58 patients
      sustained bowel, mesenteric, or pancreatic injuries (BMPI) necessitating
      laparotomy. The sensitivity, specificity, and accuracy of MDCT in identifying
      patients with active bleeding or BMPI were all 100%. CONCLUSIONS: Multidetector
      computed tomography was useful as a second line initial assessment tool to
      identify injuries and determine treatment planning in blunt abdominal trauma
      patients. No increased risk was found if the facility is readily available, the
      protocol is well designed, and the patient is well prepared.

PMID- 16411015
TI  - Intracerebral microdialysis in neurosurgical intensive care patients utilising
      catheters with different molecular cut-off (20 and 100 kD).
AB  - OBJECTIVE: To compare the properties of a new intracerebral micro-dialysis
      catheter with a high cut-off membrane (molecular cut-off 100 kDalton) with a
      standard catheter (CMA70, molecular cut-off 20 kDalton). METHODS: Paired
      intracerebral microdialysis catheters were inserted in fifteen comatose patients
      treated in a neurosurgical intensive care unit following subarachnoid haemorrhage
      or traumatic brain injury. The high-cut-off catheter (D(100)) differed from the
      CMA 70 catheter by the length (20 mm) and cut-off properties of the catheter
      membranes (100 kDalton) and the perfusion fluids used (Ringer-Dextran 60).
      Samples were collected every 4-6 hours, analyzed bedside (for glucose, glutamate,
      glycerol, lactate, pyruvate and urea) and later in the laboratory (for total
      protein). RESULTS: Fluid recovery was similar for the two types of catheters, but
      significantly more protein was recovered by the D(100) catheter. The recovery of
      glycerol and pyruvate did not differ, while minor differences in recovery of
      glutamate and glucose were observed. The recovery of lactate was considerably
      lower in the D(100) catheter (p < 0.01), influencing the lactate/pyruvate-ratio.
      The patterns of concentration changes over time were consistent for all
      metabolites, and independent of type of catheter. CONCLUSION: Microdialysis
      catheters with high cut-off membranes can be used in routine clinical practice in
      the NSICU, adding the possibility of macro-molecule sampling from the
      extracellular space during monitoring.

PMID- 16411016
TI  - Genome histories clarify evolution of the expansin superfamily: new insights from
      the poplar genome and pine ESTs.
AB  - Expansins comprise a superfamily of plant cell wall-loosening proteins that has
      been divided into four distinct families, EXPA, EXPB, EXLA and EXLB. In a recent
      analysis of Arabidopsis thaliana and Oryza sativa expansins, we proposed a
      further subdivision of the families into 17 clades, representing independent
      lineages in the last common ancestor of monocots and eudicots. This division was
      based on both traditional sequence-based phylogenetic trees and on position-based
      trees, in which genomic locations and dated segmental duplications were used to
      reconstruct gene phylogeny. In this article we review recent work concerning the
      patterns of expansin evolution in angiosperms and include additional insights
      gained from the genome of a second eudicot species, Populus trichocarpa, which
      includes at least 36 expansin genes. All of the previously proposed monocot
      eudicot orthologous groups, but no additional ones, are represented in this
      species. The results also confirm that all of these clades are truly independent
      lineages. Furthermore, we have used position-based phylogeny to clarify the
      history of clades EXPA-II and EXPA-IV. Most of the growth of the expansin
      superfamily in the poplar lineage is likely due to a recent polyploidy event.
      Finally, some monocot-eudicot clades are shown to have diverged before the
      separation of the angiosperm and gymnosperm lineages.

PMID- 16411017
TI  - Female pelvic floor dysfunction in the Middle East: a tale of three factors-
      culture, religion and socialization of health role stereotypes.

PMID- 16411018
TI  - Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty
      acid binding protein gene.
AB  - Fatty acids are shown to be important in various skin functions. Fatty acid
      binding protein (FABP) is postulated to serve as a lipid shuttle, solubilizing
      hydrophobic fatty acids and delivering them to the appropriate metabolic system.
      Among the FABP family proteins, epidermal-type FABP (E-FABP) is solely expressed
      in keratinocyte but its specific role in skin is not yet fully established. We
      found an elevated expression of E-FABP in regenerative keratinocytes of healing
      wounds. However, E-FABP null mice showed no marked differences compared to wild
      type mice in the process of wound closure, in vivo. On the other hand, in
      keratinocyte culture, E-FABP gene disruption decreased the cell motility, but did
      not affect the cell proliferation. E-FABP deletion may be compensated for in vivo
      by the microenvironment comprised of various cells such as fibroblasts and
      endothelial cells around the wound. Our analyses suggest that the E-FABP
      elevation may be necessary for the activation of cell motility within
      regenerative epidermis during wound healing.

PMID- 16411019
TI  - ACBP--a PPAR and SREBP modulated housekeeping gene.
AB  - The acyl-CoA binding protein (ACBP) is a 10 kD intracellular lipid binding
      protein that binds and transports acyl-CoA esters. The protein is expressed in
      most cell types at low levels; however, expression differs markedly between
      different cell types with expression being particularly high in e.g. cells with a
      high turnover of fatty acids. We show here that the relatively high basal
      promoter activity of the rat ACBP gene in fibroblasts and hepatoma cells relies
      on sequences between -331 to -182 and on the Sp1 and NF-Y sites at -172 and -143,
      respectively. The basal transcription is modulated by members of the PPAR and
      SREBP families. In adipocytes, PPARgamma is in part responsible for the induction
      during adipocyte differentiation, but other transcription factors appear to play
      a role as well. In hepatocytes, SREBP-1c is the main regulator of ACBP in
      response to changes in insulin levels during fasting/refeeding. PPARalpha
      counteracts this effect by stimulating ACBP expression during fasting. In
      addition, PPARalpha mediates the induction of ACBP expression in response to
      peroxisome proliferators. PPARalpha and PPARgamma do not require sequences
      upstream of -182 for transactivation; however, SREBP-1c requires the synergistic
      action of sequences in intron 1 for transactivation of the ACBP promoter.

PMID- 16411020
TI  - Dissociation and unfolding of inducible nitric oxide synthase oxygenase domain
      identifies structural role of tetrahydrobiopterin in modulating the heme
      environment.
AB  - The oxygenase domain of the inducible nitric oxide synthase, Delta65 iNOSox is a
      dimer that binds heme, L-Arginine (L-Arg), and tetrahydrobiopterin (H(4)B) and is
      the site for NO synthesis. The role of H(4)B in iNOS structure-function is
      complex and its exact structural role is presently unknown. The present paper
      provides a simple mechanistic account of interaction of the cofactor
      tetrahydrobiopterin (H(4)B) with the bacterially expressed Delta65 iNOSox
      protein. Transverse urea gradient gel electrophoresis studies indicated the
      presence of different conformers in the cofactor-incubated and cofactor-free
      Delta65 iNOSox protein. Dynamic Light Scattering (DLS) studies of cofactor
      incubated and cofactor-free Delta65 iNOSox protein also showed two distinct
      populations of two different diameter ranges. Cofactor tetrahydrobiopterin
      (H(4)B) shifted one population, with higher diameter, to the lower diameter
      ranges indicating conformational changes. The additional role played by the
      cofactor is to elevate the heme retaining capacity even in presence of denaturing
      stress. Together, these findings confirm that the H(4)B is essential in
      modulating the iNOS heme environment and the protein environment in the dimeric
      iNOS oxygenase domain.

PMID- 16411021
TI  - Down regulation of N-acetylglucosaminyltransferase V facilitates all
      transretinoic acid to induce apoptosis of human hepatocarcinoma cells.
AB  - After N-acetylglucosaminyltransferase V (GnT-V) activity was down-regulated by
      the transfection of its antisense cDNA(GnTV-AS), apoptosis of H7721 cells was
      appeared and the apoptosis induced by 80 microM all-transretinoic acid (ATRA) was
      facilitated, while ATRA itself could not induce apparent apoptosis in mock cells
      transfected with the vector. In the study of the molecular mechanism of this
      phenomenon, it was found that GnTV-AS reduced the expressions of anti-apoptotic
      proteins, such as phosphorylated protein kinase B and phosphorylated Bad as well
      as Bcl-2 and Bcl-X (L), and elevated those of pro-apoptotic proteins, including
      Bax, full length caspase-3 and its activated fragments as well as anti
      oncoprotein p53. In the contrast, ATRA up regulated the expressions of Bax and
      activated caspase-3 fragments only. After the GnTV-AS transfected cells were
      treated with ATRA, phosphorylated PKB and Bad were further decreased, while Bax
      and activated caspase-3 fragment were further increased, leading to the enhanced
      apoptosis in flow-cytometry analysis when compared with GnTV-AS cells not treated
      with ATRA. It was speculated that the decreased phospho-Bad resulted from the
      reduced phospho-PKB and the up regulation of p53 caused the elevated activity of
      Bax. The increased active caspase-3 was the consequence of the elevated Bax/ Bcl
      2(Bcl-X(L)) activity ratio in the cells.

PMID- 16411022
TI  - Antimicrobial actions of human and macaque sperm associated antigen (SPAG) 11
      isoforms: influence of the N-terminal peptide.
AB  - In addition to their role in sperm maturation, recent evidence has indicated that
      epididymal proteins have a role in male reproductive tract innate immunity.
      Herein we demonstrate that human and macaque epididymal protein isoforms in the
      SPAG (sperm associated antigen) 11 family, full length SPAG11C, K and L exhibit
      potent antibacterial activity against E. coli. Analysis of activities of the N-
      and C-terminal domains revealed that the human N-terminal peptide is
      bactericidal, while the C-terminal domains that contain the defensin-like 6
      cysteine array in SPAG11C and partial arrays in SPAG11K and SPAG11L, lack
      antibacterial activity. The N-terminal peptide does not appear to contain all the
      determinants of activity since full-length human SPAG11C is more active than the
      isolated N-terminal peptide and since sulfhydryl reduction and alkylation, which
      would affect primarily the C-terminal peptides, completely abolished activities
      of the whole proteins. These results suggest that the structure conferred by the
      disulfide bonds in human SPAG11C contributes to the antibacterial activity of the
      whole molecule. The activities of the N-terminal peptide and of full length human
      SPAG11C were somewhat reduced in increasing NaCl concentrations. In contrast, the
      antibacterial activities of full length macaque SPAG11C, K and L were unaffected
      by the presence of NaCl suggesting a mechanism in the macaque that is less
      dependent upon electrostatic interactions. SPAG11C, K and L disrupted E. coli
      membranes but had no effect on erythrocyte membranes. Inhibition of E. coli RNA,
      DNA and protein synthesis by nonlethal concentrations of SPAG11 isoforms
      indicated an additional mechanism of bacterial killing.

PMID- 16411024
TI  - Atypical teratoid/rhabdoid tumor of the spinal canal.

PMID- 16411023
TI  - Protection against myocardial ischaemia/reperfusion injury by PPAR-alpha
      activation is related to production of nitric oxide and endothelin-1.
AB  - BACKGROUND: Ligands of peroxisome proliferator-activated receptor alpha (PPAR
      alpha) have been shown to reduce ischaemia/reperfusion injury. The mechanisms
      behind this effect are not well known. We hypothesized that activation of PPAR
      alpha exerts cardioprotection via a mechanism related to nitric oxide (NO) and
      endothelin-1 (ET-1). METHODS: Five groups of anaesthetized open-chest Sprague
      Dawley rats were given the PPAR-alpha agonist WY 14643 1 mg/kg (WY; n = 7),
      dimethyl sulfoxide (DMSO, vehicle for WY; n = 6), the combination of WY and the
      NO synthase inhibitor N-nitro-L-arginine (L-NNA, 2 mg/kg) (n = 7), L-NNA only (n
      = 8) or 0.9% sodium chloride (NaCl, vehicle for DMSO and L-NNA; n = 8) i.v.
      before a 30 min period of coronary artery occlusion followed by 2 h of
      reperfusion. Infarct size (IS), eNOS and iNOS protein and ET-1 mRNA expression
      were determined. RESULTS: There were no haemodynamic differences between the
      groups during the experiment. The IS was 78 +/- 3% of the area at risk in the
      DMSO group and 77 +/- 2% in the NaCl group (P = NS). WY reduced IS to 56 +/- 3%
      (P < 0.001 vs. DMSO group). When WY was administered in combination with L-NNA
      the cardioprotective effect was abolished (IS 73 +/- 3%, P < 0.01 vs. WY 14643).
      L-NNA did not affect IS per se (78 +/- 2%, P = NS). The expression of eNOS but
      not iNOS protein in ischaemic myocardium from rats was increased in the group
      given WY (P < 0.05). ET-1 mRNA levels were lower in the ischaemic myocardium
      following WY administration. CONCLUSION: The results suggest that the PPAR-alpha
      activation protects the rat myocardium against ischaemia/ reperfusion injury via
      a mechanism related to production of NO, and possibly ET-1.

PMID- 16411025
TI  - Diffusion-weighted MRI correlates of subacute methotrexate-related neurotoxicity.
AB  - OBJECTIVES: A delayed stroke-like leukoencephalopathy has been observed in
      patients receiving methotrexate (MTX) for childhood leukemia. Diffusion-weighted
      MRI (DWI) may help to distinguish between ischemic stroke and chemotherapy
      related leukoencephalopathy. Although conventional MRI correlates have been
      described for this stroke-like syndrome, DWI data are largely unavailable. Our
      objective is to present a retrospective analysis of the DWI findings in four
      patients who suffered subacute neurotoxicity after intrathecal MTX. DESIGN: We
      reviewed the medical records of four patients, who were seen by us between July
      2000 and February 2004 for sudden onset of a central neurological syndrome within
      days of intrathecal MTX. Patients underwent standardized MRI within 48 h of
      symptom onset; MRI included DWI and apparent diffusion coefficient (ADC) maps.
      RESULTS: DWI of all patients revealed well-demarcated hyperintense lesions within
      the subcortical white matter corresponding to areas of restricted proton
      diffusion on ADC maps. Lesions exceeded the confines of adjacent vascular
      territories. Complete resolution of symptoms within 1-4 days was accompanied by
      normalization of ADC abnormalities. CONCLUSIONS: DWI findings in this cohort seem
      to reflect cytotoxic edema within cerebral white matter suggesting a reversible
      metabolic derangement, rather than ischemia, as the basis for this syndrome.

PMID- 16411026
TI  - Do clinical marker states improve responsiveness and construct validity of the
      standard gamble and feeling thermometer: a randomized multi-center trial in
      patients with chronic respiratory disease.
AB  - BACKGROUND: Optimizing the validity and responsiveness of utility measures will
      enhance their usefulness in randomized trials. We evaluated the impact of
      clinical marker state (CMS) rating prior to patients' rating their own health on
      two utility instruments (feeling thermometer (FT) and standard gamble (SG)) in
      patients with chronic respiratory disease (CRD). METHODS: We randomized 182
      patients with CRD to complete the FT (self-administered) and SG with CMS
      (FT+/SG+, n=91) or without marker states (FT-/SG-, n=91) before and after
      undergoing respiratory rehabilitation in a multi-center trial. RESULTS: Use of
      CMS did not influence baseline utility scores. Improvement after therapy on the
      scale from 0 (dead) to 1.0 (full health) was 0.04 both in FT+ (p=0.03) and FT-
      (p=0.02; the difference between FT+ and FT- was 0.00, p=0.83). Improvement on the
      SG was 0.05 in both SG+ (p=0.08) and SG- (p=0.04; difference between SG+ and SG-
      0.00, p=0.95). Correlations with other health related quality of life scores were
      highest for FT+. CONCLUSION: Administration of CMS did not improve responsiveness
      of the FT but may have improved construct validity. The SG showed limited
      construct validity and responsiveness that was not influenced by CMS use.

PMID- 16411028
TI  - Bipolar disorder and quality of life: a patient-centered perspective.
AB  - OBJECTIVES: Several quantitative studies have now examined the relationship
      between quality of life (QoL) and bipolar disorder (BD) and have generally
      indicated that QoL is markedly impaired in patients with BD. However, little
      qualitative research has been conducted to better describe patients' own
      experiences of how BD impacts upon life quality. We report here on a series of in
      depth qualitative interviews we conducted as part of the item generation phase
      for a disease-specific scale to assess QoL in BD. METHODS: We conducted 52
      interviews with people with BD (n=35), their caregivers (n=5) and health care
      professionals (n=12) identified by both convenience and purposive sampling.
      Clinical characteristics of the affected sample ranged widely between individuals
      who had been clinically stable for several years through to inpatients who were
      recovering from a severe episode of depression or mania. Interviews were tape
      recorded, transcribed verbatim and analyzed thematically. RESULTS: Although
      several interwoven themes emerged from the data, we chose to focus on 6 for the
      purposes of this paper: routine, independence, stigma and disclosure, identity,
      social support and spirituality. When asked to prioritize the areas they thought
      were most important in determining QoL, the majority of participants ranked
      social support as most important, followed by mental health. CONCLUSIONS:
      Findings indicate that there is a complex, multifaceted relationship between BD
      and QoL. Most of the affected individuals we interviewed reported that BD had a
      profoundly negative effect upon their life quality, particularly in the areas of
      education, vocation, financial functioning, and social and intimate
      relationships. However, some people also reported that having BD opened up new
      doors of opportunity.

PMID- 16411027
TI  - Do the SF-36 and WHOQOL-BREF measure the same constructs? Evidence from the
      Taiwan population*.
AB  - BACKGROUND: The SF-36 and WHOQOL-BREF are available for international use, but it
      is not clear if they measure the same constructs. We compared the psychometric
      properties and factor structures of these two instruments. METHODS: Data were
      collected from a national representative sample (n=11,440) in the 2001 Taiwan
      National Health Interview Survey, which included Taiwan versions of the SF-36 and
      WHOQOL-BREF. We used Cronbach's alpha coefficient to estimate scale reliability.
      We conducted exploratory factor analysis to determine factor structure of the
      scales, and applied multi trait analysis to evaluate convergent and discriminant
      validity. We used standardized effect size to compare known-groups validity for
      health-related variables (including chronic conditions and health care
      utilization) and self-reported overall quality of life. Structural equation
      modeling was used to analyze relationships among the two SF-36 component scales
      (PCS and MCS) and the four WHOQOL subscales (physical, psychological, social
      relations, and environmental). RESULTS: Cronbach's alpha coefficients were
      acceptable ([Symbol: see text]0.7) for all subscales of both instruments. The
      factor analysis yielded two unique factors: one for the 8 SF-36 subscales and a
      second for the 4 WHOQOL subscales. Pearson correlations were weak (<0.3) among
      subscales of both instruments. Correlations for subscales hypothesized to measure
      similar constructs differed little from those measuring heterogeneous subscales.
      Effect sizes suggested greater discrimination by the SF-36 for health status and
      services utilization known groups, but greater discrimination by the WHOQOL for
      QOL-defined groups. Structural equation modeling suggested that the SF-36 PCS and
      MCS were weakly associated with WHOQOL. CONCLUSIONS: In this Taiwan population
      sample, the SF-36 and WHOQOL-BREF appear to measure different constructs: the SF
      36 measures health-related QOL, while the WHOQOL-BREF measures global QOL.
      Clinicians and researchers should carefully define their research questions
      related to patient-reported outcomes before selecting which instrument to use.

PMID- 16411029
TI  - Quality of life in depression: predictive models.
AB  - The purpose of this study was to examine the predictive factors of quality of
      life for inpatients with depressive disorders. Eighty-three patients (mean age
      44; 73% female) with depressive disorders were recruited from the psychosomatic
      ward of a medical center in the northern part of Taiwan. The predictive models of
      this study were established by encompassing three constructs: clinical variables,
      demographics, and perceived competence. The outcome variables of this study
      included an overall quality of life score and four domains' scores of the World
      Health Organization Quality of Life-brief version (WHOQOL-BREF). Stepwise
      regression analysis was used to identify significant factors related to the
      outcome variables. The results showed that there were five distinct models for
      the various domains of the quality of life. The predictive variables of the final
      model for overall quality of life included: the Beck Anxiety Inventory, the
      Canadian Occupational Performance Measure-satisfaction, and the Occupational Self
      Assessment-self. For the physical domain of the quality of life model, the
      adjusted Beck Depression Inventory-II, the Beck Anxiety Inventory, and the
      Activity of Daily Living Inventory were the significant predictors. In the
      psychological domain, the adjusted Beck Depression Inventory-II and age were the
      predictive factors. The adjusted Beck Depression Inventory-II, the Beck Anxiety
      Inventory and the Occupational Self Assessment-environment were the predictors
      for the social domain of quality of life. Finally, the adjusted Beck Depression
      Inventory-II, age, and the Occupational Self Assessment-environment were the
      predictors for the environmental domain of quality of life. The significance of
      the perceived competence variables in the quality of life of patients with
      depression indicates that occupational therapy intervention is warranted.

PMID- 16411030
TI  - Negative mood and quality of life in patients with asthma.
AB  - The aim of this study was to evaluate the effect of negative mood states at the
      moment of questionnaire, and other patient and disease characteristics on quality
      of life (QoL) in patients with asthma. The study groups were composed of 116
      stable adult asthmatic patients and 116 age and sex matched healthy subjects. We
      used Short-Form Health Survey-36 (SF-36) for the assessment of general QoL in all
      participants, and the Asthma Quality of Life Questionnaire (AQLQ) for the
      assessment of disease specific QoL in patients with asthma. We evaluated negative
      mood in all subjects with a questionnaire including six mood subscales in three
      categories (nervous-anxious, hostile-angry and fearful-panicky). Negative mood
      scores were not different between asthmatic and comparison groups (p=0.4), but
      both SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
      scores were significantly lower in asthmatic group (p=0.003 and p=0.001,
      respectively). Multiple linear regression analysis in all study population
      indicated that both reduced PCS and MCS scores of SF-36 were associated with
      negative mood score (beta=-0.28, p<0.001 and beta=-0.37, p<0.001, respectively)
      and with FEV(1)% (beta=0.19, p=0.001 and beta=0.25, p<0.001, respectively) after
      adjusting for age, female sex, and the presence of asthma. On the other hand,
      multiple linear regression analysis in patients with asthma revealed that
      negative mood score and disease severity score were significant predictors for
      overall score of AQLQ after adjusting for other patient and disease
      characteristics (beta=-0.17, p=0.008 and beta=-0.64, p<0.001, respectively). The
      level of negative mood and disease severity in asthmatics significantly impair
      QoL. Thus, considering that one of the main objectives of health care should be
      preserving a satisfactory QoL in asthmatics, the presence and seriousness of
      negative mood and their effects on QoL should be taken into account as part of
      the clinical evaluation in asthmatics.

PMID- 16411031
TI  - The relationship between patient knowledge of hemoglobin levels and health
      related quality of life.
AB  - BACKGROUND: An anti-anemia drug may improve self-reported quality of life (QOL)
      partly because patients know their hemoglobin level is rising. In the absence of
      any published studies on this topic, the authors investigated the association
      between knowledge of hemoglobin levels and self-reported QOL. METHODS: The study
      analyzed health-related QOL (HRQOL) data from five randomized clinical trials of
      erythropoietic therapy in patients with cancer-related anemia. Patients were
      asked whether they knew their hemoglobin level and, if so, to report its value.
      Patients (n=1007) were grouped into three categories depending on the extent and
      accuracy of hemoglobin level knowledge. HRQOL scale scores were compared between
      categories. RESULTS: Only 23.2% of patients reported knowing their hemoglobin
      level at the end of the study; however, the value was accurate (within 1 g/dl) in
      88.0% of these patients. On five of the 11 HRQOL scales studied, there was a
      significant association between knowledge of hemoglobin level and HRQOL score.
      However, the magnitude of the mean difference between those who knew vs. those
      who did not know their hemoglobin was generally below scale thresholds for
      minimally important differences. CONCLUSIONS: Patient knowledge of hemoglobin
      level has a modest association with some aspects of self-reported HRQOL. The
      magnitude of this association, where it exists, would be unlikely to explain
      large group differences in HRQOL reports over time, even for patients who know
      their hemoglobin level.

PMID- 16411033
TI  - Relationship between multimorbidity and health-related quality of life of
      patients in primary care.
AB  - Previous studies about the association of multimorbidity and the health-related
      quality of life (HRQOL) in primary-care patients are limited because of their
      reliance on simple counts of diseases from a limited list of diseases and their
      failure to assess the severity of disease. We evaluated the association while
      taking into account the severity of the medical conditions based on the
      Cumulative Illness Rating Scale (CIRS) score, and controlling for potential
      confounders (age, sex, household income, education, self-perception of economic
      status, number of people living in the same dwelling, and perceived social
      support). We randomly selected 238 patients to construct quintiles of increasing
      multimorbidity (CIRS). Patients completed the 36-item Medical Outcomes study
      questionnaire (SF-36) to evaluate their HRQOL. Applying bivariate and
      multivariate linear regression analyses, we used the CIRS as either a continuous
      or a categorical (quintiles) variable. Use of the CIRS revealed a stronger
      association of HRQOL with multimorbidity than using a simple count of chronic
      conditions. Physical more than mental health deteriorated with increasing
      multimorbidity. Perceived social support and self-perception of economic status
      were significantly related to all scales of the SF-36 (p < 0.05). Increased
      multimorbidity adversely affected HRQOL in primary-care adult patients, even when
      confounding variables were controlled for.

PMID- 16411032
TI  - The effect of diagnosis with HIV infection on health-related quality of Life.
AB  - We sought to understand how diagnosis with HIV affects health-related quality of
      life. We assessed health-related quality of life using utility-based measures in
      a Department of Veterans Affairs (VA) clinic and a University-based clinic.
      Respondents assessed health-related quality of life regarding their current
      health, and retrospectively assessed their health 1 month prior to and 2 months
      after diagnosis with HIV infection. Sixty-six patients completed the study. The
      overall mean utilities for health 1 month before and 2 months after diagnosis
      were 0.87 (standard error 0.037), and 0.80 (0.043) (p<0.005 by rank sign test),
      but the effect of diagnosis differed between the two clinics, with a substantial
      decrease in the university clinic and a small non-significant decrease in the VA
      clinic. The overall mean utility for current health was 0.85 (0.034), assessed on
      average 7.5 years after diagnosis. When asked directly whether diagnosis of HIV
      decreased health-related quality of life, 47% agreed, but 35% stated that HIV
      diagnosis positively affected health-related quality of life. Diagnosis with HIV
      decreased health-related quality of life at 2 months on average, but this effect
      diminished over time, and differed among patient populations. Years after
      diagnosis, although half of the patients believed that diagnosis reduced health
      related quality of life, one-third reported improved health-related quality of
      life.

PMID- 16411034
TI  - Patients' perceptions of health related quality of life in rheumatoid arthritis
      and chronic low back pain.
AB  - OBJECTIVES: To determine how health related quality of life (HRQL) is perceived
      by patients with rheumatoid arthritis (RA) and chronic low back pain (CLBP) using
      a textual analysis approach. PATIENTS: Two-hundred and forty-eight outpatients
      (85% female), mean age 58+/-13 years (40% RA and 60% CLBP). METHODS:
      Observational descriptive study. Sociodemographic and clinical variables were
      determined. A questionnaire was designed which included an open question "What
      does health related quality of life mean to you." which patients answered in
      writing. Textual data analysis was performed using a previous described method
      based on multivariate descriptive statistical methods. RESULTS: The two groups
      were homogenous with respect to gender, educational level, disease duration,
      comorbid conditions and global functional status. Patients with RA and CLBP used
      clearly differentiated terms to describe HRQL (RA: to be able (capable), house;
      CLBP: life, health, quality). RA patients were specific and primarily concerned
      with functional status and CLBP patients with health and life. The most
      characteristic phrase used by RA patients was: "to be able to do housework" and
      for CLBP: "health is the most important thing for quality of life." In the
      factorial representation, the two pathologies were markedly separated.
      CONCLUSIONS: A series of characteristic answers on HRQL may be identified in
      patients with RA and CLBP, showing that they have different perceptions about
      what HRQL is according to their pathology. The use of open questions in a group
      of homogenous patients with specific pathologies could result in more disease
      specific responses. Textual statistical analysis of open questions may provide
      more information than standard methods, and may be considered as valid for the
      analysis of subjective issues such as quality of life.

PMID- 16411035
TI  - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of
      health-related quality of life and quality of life for patients with pulmonary
      hypertension.
AB  - OBJECTIVE: No outcome measures specific to pulmonary hypertension (PH) currently
      exist. The aim of the study was to develop health-related quality of life
      (symptoms and functioning) scales and a quality of life scale that would allow
      comprehensive, accurate and valid patient-reported outcome assessment in clinical
      studies. METHODS: The content of the Cambridge Pulmonary Hypertension Outcome
      Review (CAMPHOR) was derived from qualitative interviews conducted with 35
      patients. Item reduction was based on the analysis of responses to a postal
      survey (n=75) and patient interviews (n=15) designed to determine face and
      content validity. A final postal validation study (n=91) was performed to
      determine reproducibility and construct validity. RESULTS: The questionnaire was
      well received by participants who found it to be relevant, comprehensible and
      quick and easy to complete. Rasch and factor analyses were conducted to ensure
      unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of
      Energy, Breathlessness and Mood subscales), Functioning and Quality of life. The
      CAMPHOR scales had good internal consistency (alpha=0.90-0.92) and
      reproducibility (test-retest correlations=0.86-0.92). They also exhibited
      convergent, divergent and known groups validity. CONCLUSIONS: The CAMPHOR is a
      valuable new instrument for assessing patient-reported outcome in PH clinical
      trials and routine practice.

PMID- 16411036
TI  - Validation of the adult attention-deficit/hyperactivity disorder quality-of-life
      Scale (AAQoL): a disease-specific quality-of-life measure.
AB  - INTRODUCTION: A growing body of evidence suggests that symptoms of attention
      deficit/hyperactivity disorder (ADHD) persist into adulthood and are associated
      with ongoing impairment and co-morbidity. The absence of a conceptually sound and
      well-validated ADHD-specific quality-of-life measure has been an obstacle to
      understanding this impact. To address this gap, the Adult ADHD Quality-of-Life
      Scale (AAQoL) was developed based on well accepted methods for designing patient
      reported outcomes. The purpose of this study was to validate the AAQoL. METHODS:
      Nine Hundred and Eighty Nine adults in a retrospective cohort study were
      administered the AAQoL and psychometric validation was conducted according to an
      a priori statistical analysis plan. RESULTS: A 29-item AAQoL was found to have
      robust scale structure with four domains: Life Productivity, Psychological
      Health, Relationships and Life outlook. Internal consistency was adequate (0.93
      for overall, 0.75-0.93 for subscales), and construct and known-groups validity
      were supported. conclusion: The AAQoL appears to be a valid measure of quality of
      life for adults with ADHD and can be considered for incorporation into future
      studies. The ability to quantify the quality-of-life consequences of adult ADHD
      should facilitate future research, assist clinicians in identifying appropriate
      treatment targets and contribute to the ultimate goal of improving the well-being
      and functioning of adults with ADHD.

PMID- 16411037
TI  - Two kinds of items in quality of life instruments: 'indicator and causal
      variables' in the EORTC qlq-c30.
AB  - Two kinds of variables may be differentiated within instruments measuring health
      related quality of life (HRQOL). Physical symptoms may be called causal variables
      because their occurrence can cause a change in HRQOL, but poor HRQOL need not
      necessarily imply that a patient suffers from these symptoms. Other items can be
      regarded as indicator variables. They reflect the level of HRQOL and a patient
      with a poor HRQOL is likely to have low scores on all indicator variables. The
      aim of this study was to test the relationship of the latent HRQOL construct to
      items and domains on the EORTC QLQ-C30. Confirmatory factor analysis was
      performed on EORTC QLQ-C30 data from 205 gastrointestinal cancer patients
      assessed one month after surgery. Functioning scales were established as
      variables indicating the level of HRQOL whereas all other subscales and items
      were established as variables causing a change in HRQOL. The model-data fit was
      satisfactory. Results support the hypothesis that two kinds of variables may be
      differentiated within HRQOL instruments. Further research should investigate
      whether both kinds of variables could be combined into a higher order, aggregate
      score for HRQOL.

PMID- 16411039
TI  - Health status measures in young people's cancer trials; a time to move health
      Related quality of life up to primary outcome measures.

PMID- 16411038
TI  - Health status in survivors of cancer in childhood and adolescence.
AB  - BACKGROUND: Assessing health status in survivors of childhood cancer is
      increasingly important due to improved survival rates. However, there are limited
      estimates available for this population based on large samples and compared to
      population controls. METHODS: In a retrospective cohort study, 2,152 long-term
      survivors and 2,432 controls, aged 5-37, who had survived cancer during childhood
      or adolescence were compared on the Health Utilities Index Mark III (HUI3).
      Descriptive and logistic regression analyses were used to assess the effect of
      age at diagnosis, type of cancer and therapy received on HUI3 domains. MAJOR
      FINDINGS: More survivors than controls showed deficits in dexterity, ambulation,
      hearing, speech and cognition but not in vision, emotion or pain. The largest
      numbers of survivors reporting excess impairment was found in the cognition
      attribute. Survivors of central nervous system tumors were most likely to show
      impairments across multiple domains. Lastly, impairments in cognition were found
      most commonly in survivors exposed to cranio-spinal radiation at young ages.
      CONCLUSIONS: Seventy-five percent of childhood cancer survivors and 80% of
      controls were found to have two or fewer impaired attributes. Those reporting
      impairments that were most likely to be of clinical relevance were among
      survivors diagnosed with central nervous system and bone tumours, and those
      exposed to cranial radiation as young children. Tools assessing health status
      should be included in prospective trials to more clearly assess the contribution
      of therapy to reduced long-term health status.

PMID- 16411040
TI  - Korean translation and validation of the functional assessment of cancer therapy
      lung (FACT-L) version 4.
AB  - In this study, we have translated and cross-culturally adapted the Functional
      Assessment of Cancer Therapy-Lung (FACT-L) version 4 into Korean, and we have
      evaluated its reliability and validity. The FACT-L version 4 was translated into
      Korean following the standard Functional Assessment of Chronic Illness Therapy
      (FACIT) translation methodology. The psychometric properties of the FACT-L were
      evaluated in 122 lung cancer patients (mean age, 60.88 years). Pre-testing was
      performed in 22 patients, and these results indicated good content coverage and
      overall comprehensibility. In validating the FACT-L version 4, our results
      indicated high internal consistency of the FACT-L scales, with Cronbach's alpha
      coefficients ranging from 0.52 to 0.84. The FACT-L also demonstrated good
      convergent and divergent validity when correlated with the Functional Living
      Index-Cancer (FLIC) and the shortened forms of the Profile of Mood States (POMS).
      This reliable and valid instrument can now be used to properly evaluate the
      quality of life of Korean lung cancer patients.

PMID- 16411041
TI  - The European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire (EORTC QLQ-C30): validation study of the Thai version.
AB  - The objective of this study was to assess the psychometric properties of the Thai
      version of the European Organization for Research and Treatment of Cancer Quality
      of Life Questionnaire (EORTC QLQ-C30) version 3.0. The questionnaire was
      completed by 310 cancer patients during their follow-up at 2 teaching hospital
      oncology clinics. About 70% of participants had advanced stage of cancer and 72%
      had been receiving chemotherapy. Cronbach's alpha coefficients of the six scales
      were above 0.7, except for cognitive and social function scales. All test-retest
      reliability coefficients were high. Multi trait scaling analysis showed that all
      item-scale correlation coefficients met the standards of convergent and
      discriminant validity. Most scales and items could discriminate between subgroups
      of patients with different clinical status assessed with the Eastern Cooperative
      Oncology Group (ECOG) scale. The results suggested that the EORTC QLQ-C30 and the
      Functional Assessment of Cancer Therapy - General (FACT-G) measured different
      aspects of quality of life and should be independently used. Testing psychometric
      properties of the EORTC QLQ-C30 in heterogeneous diagnostic group yield similar
      results as found in homogeneous group. These results support that the EORTC QLQ
      C30 (version 3.0) has proven to be a reliable and valid measure of the quality of
      life in Thai patients with various types of cancer.

PMID- 16411042
TI  - Quality of life and body image in the assessment of psychological impact of
      lipodystrophy: validation of the Italian version of assessment of body change and
      distress questionnaire.
AB  - Lipodystrophy (LD) includes morphologic changes that are distressing to patients
      with HIV. We tested the validity of an Italian version of the Assessment of Body
      Change and Distress (ABCD) questionnaire and analysed its relationship to
      physical and mental aspects of Health-Related Quality of Life. Two hundred and
      fifty-two patients completed the questionnaires. Construct validity of the ABCD
      was tested against the MOS-HIV Health Survey, body mass-index (BMI) and CD4+ T
      lymphocyte counts. Cronbach's alpha for the ABCD total score was 0.94. The ABCD
      showed the hypothesized moderate correlations to MOS-HIV scales and clinical
      variables. Preliminary evidence supports the reliability and validity of the
      Italian version of the ABCD in people with HIV and LD. This questionnaire may be
      useful to identify people experiencing greater impact of LD, or to evaluate the
      impact of interventions to treat LD such as plastic surgery.

PMID- 16411043
TI  - Validation of the Dutch version of the CDC core healthy days measures in a
      community sample.
AB  - An important disadvantage of most indicators of health related quality of life
      used in public health surveillance is their length. In this study the authors
      investigated the reliability and validity of a short indicator of health related
      quality of life, the Dutch version of the four item 'CDC Core Healthy Days
      Measures' (CDC HRQOL-4). The reliability was evaluated by calculating Cronbach's
      alpha of the CDC HRQOL-4. The concurrent validity was tested by comparing the CDC
      HRQOL-4 with three other indicators of health related quality of life, the SF-36,
      the WHOQoL-BREF and the GHQ-12. The construct validity was evaluated by assessing
      the ability of the CDC HRQOL-4 to discriminate between respondents with and
      without a (non-mental) chronic condition, depression, a visit to the general
      practitioner and use of prescription drugs. Randomly sampled respondents from the
      city of Utrecht were asked to fill in a questionnaire. 659 respondents (response
      rate 45%) completed the questionnaire. Participants represented the adult, non
      institutionalised population of the city of Utrecht, the Netherlands: 58% women;
      mean age 41 years; 15% of non-Dutch origin. The reliability of the CDC HRQOL-4
      was good. Cronbach's alpha of three of the four CDC HRQOL-4-items was 0.77 which
      is good for internal consistent scales. The concurrent validity was good. The
      four items of the CDC HRQOL-4 showed higher correlations with their corresponding
      domains of the other instrument than the other domains. Comparison of respondents
      with or without a chronic condition, depression, visit to the GP and use of
      prescription drugs produced evidence for an excellent construct validity of the
      CDC HRQOL-4.

PMID- 16411046
TI  - A weight loss trial for breast cancer recurrence: pre-menopausal, post
      menopausal, both, or neither?

PMID- 16411047
TI  - Are findings from studies of obesity and prostate cancer really in conflict?
AB  - Recent studies on the association between obesity and prostate cancer appear to
      be in conflict. A recent prospective cohort study reported that the incidence of
      prostate cancer was lower among obese men under the age of 60 years and among
      those men with a family history of prostate cancer. Similarly, a case-control
      study found obesity was inversely associated with prostate cancer risk in men
      aged 40-64 years. However, several prospective cohort studies found that obese
      men are more likely to die from prostate cancer than non-obese men. Finally, two
      recent studies found that among men with prostate cancer, obese men were more
      likely to have a biochemical progression after surgery. We postulate that by
      closely examining the comparison groups used in these studies, these findings
      may, in fact, be in agreement. Specifically, this paradox within the literature
      may result from the possibility that obesity influences the development of
      aggressive (i.e., higher stage, higher grade, recurrence, death) and non
      aggressive disease differently. We suggest that obesity may reduce the risk of
      non-aggressive disease but simultaneously increase the risk of aggressive
      disease. Finally, additional methodological issues are discussed that
      investigators need to be aware of to be able to draw inferences across studies of
      obesity and prostate cancer outcomes.

PMID- 16411048
TI  - Pregnancy history and incidence of melanoma in women: a pooled analysis.
AB  - There is evidence that pregnancy history including age at first birth and parity
      may play a role in risk of cutaneous melanoma in women, although, epidemiological
      findings are inconsistent. We conducted a collaborative analysis of these factors
      using the original data from ten completed case-control studies (2391 cases and
      3199 controls), and assessed the potential confounding effects of socioeconomic,
      pigmentary, and sun exposure-related factors. We found no overall association
      with ever having a live birth (pooled odds ratio (pOR) 0.95, 95% confidence
      interval (CI) 0.67-1.35). However, we detected a reduced risk of melanoma among
      women with higher parity (> or = 5 versus no live births pOR 0.76, 95% CI 0.49
      1.18, each live birth pOR 0.95, 95% CI 0.91-0.99, p trend = 0.05). Women with
      both earlier age at first birth (e.g., <20 years) and higher parity (e.g., > or =
      5 live births) had a particularly lower risk than women with later age at first
      birth (e.g., > or = 25 years) and lower parity (e.g., <5 live births) (pOR 0.33,
      95% CI 0.14-0.75). The results are compatible with an effect of reproductive
      history-related factors on melanoma risk, but also could reflect differences in
      other factors, such as sun exposure history.

PMID- 16411049
TI  - Trends for in situ and invasive melanoma in Queensland, Australia, 1982-2002.
AB  - OBJECTIVES: Queensland, the north-eastern state of Australia, has the highest
      incidence of melanoma in the world. Control measures started earlier here than
      probably anywhere else in the world; early detection programmes started in the
      1960s and primary prevention in the 1980s. Data from the population-based
      Queensland Cancer Registry therefore provide an internationally unique data
      source with which to assess trends for in situ and invasive melanomas and to
      consider the implications for early detection and primary prevention. METHODS: We
      used Poisson regression to estimate the annual percentage change in rates across
      21 years of incidence data for in situ and invasive lesions, stratified by age
      and sex. Joinpoint analyses were used to assess whether there had been a
      statistically significant change in the trends. RESULTS: In situ melanomas
      increased by 10.4% (95% CI: 10.1%, 11.1%) per year among males and 8.4% (7.9%,
      8.9%) per year among females. The incidence of invasive lesions also increased,
      but not as quickly; males 2.6% (2.4%, 2.8%), females 1.2% (0.9%, 1.5%). Valid
      data on thickness was only available for 1991 to 2002 and for this period thin
      invasive lesions were increasing faster than thick-invasive lesions (for example,
      among males: thin 3.8%, thick 2.0%). We found some suggestive evidence of lower
      proportionate increase for the most recent years for both in-situ and invasive
      lesions, but this did not achieve statistical significance. Among people younger
      than 35 years, the incidence of invasive melanoma was stable and there was a
      suggestion of a birth cohort effect from about 1958. Mortality rates were stable
      across all ages, and there was a suggestion of decreasing rates among young
      women, although this did not achieve statistical significance. CONCLUSION: Age
      standardised incidence is continuing to increase and this, in combination with a
      shift to proportionately more in situ lesions, suggests that the stabilisation of
      mortality rates is due, in large part, to earlier detection. For primary
      prevention, after a substantial period of sustained effort in Queensland, there
      is some suggestive, but not definitive, evidence that progress is being made.
      Incidence rates are stabilising in those younger than 35 years and the
      proportionate increase for both in situ and invasive lesions appears to be lower
      for the most recent period compared with previous periods. However, even taking
      the most favourable view of these trends, primary prevention is unlikely to lead
      to decreases in the overall incidence rate of melanoma for at least another 20
      years. Consequently, the challenge for primary prevention programmes will be to
      maintain momentum over the long term. If this can be achieved, the eventual
      public-health benefits are likely to be substantial.

PMID- 16411050
TI  - Breast cancer screening among low-income or uninsured women: results from the
      National Breast and Cervical Cancer Early Detection Program, July 1995 to March
      2002 (United States).
AB  - OBJECTIVE: To describe the results of breast cancer screening among low-income
      and uninsured women in the only national organized screening program in the US,
      the National Breast and Cervical Cancer Early Detection Program (NBCCEDP).
      METHODS: We analyzed mammography and diagnostic follow-up data for 789,647 women
      who received their first mammogram in the NBCCEDP and 454,754 subsequent
      mammograms among these women. We calculated the rate of mammograms with abnormal
      findings, diagnostic follow-up, biopsy, and cancers detected per 1000 mammograms
      by age and racial or ethnic groups. Positive Predictive Values (PPVs) were
      estimated for abnormal mammograms and biopsy. RESULTS: Nearly 64% of the women
      screened in the program were from 50 to 64 years of age and about 46% were
      members of racial or ethnic minority groups. Women aged 40 to 49 years had the
      highest rates of abnormal mammograms and of diagnostic follow-up. However, cancer
      detection rates were highest in women aged 60 to 64 years. In addition, the PPVs
      for both abnormal mammograms and biopsy were highest in the oldest age group.
      CONCLUSIONS: Cancer detection rates and PPVs for both abnormal mammograms and
      biopsy were highest in women aged 50 years or more. These results support the
      programs focus on screening women aged 50 and older for breast cancer.

PMID- 16411051
TI  - Breast cancer and night work among Norwegian nurses.
AB  - OBJECTIVE: Previous studies have suggested an association between breast cancer
      and night work. We evaluated the relationship among Norwegian nurses. METHODS: A
      case-control study, nested within a cohort of 44,835 nurses educated between 1914
      and 1980 was performed, based on a registry of all Norwegian nurses. Four
      controls were individually matched by year of birth to each of 537 breast cancer
      cases that occurred during the period 1960-1982. The reconstruction of work
      history and number of years with night work for each nurse was based on
      information from the nurse registry, and data from three censuses. We used
      conditional logistic regression to calculate odds ratios (ORs) and 95% confidence
      intervals (CIs), adjusted for total duration of work as a nurse and parity. All
      statistical tests were two-sided. RESULTS: The adjusted OR of breast cancer among
      nurses who worked nights for 30 or more years was 2.21 (CI 1.10-4.45) compared
      with those who did not work nights after graduation from nursing school (p(trend)
      = 0.01). CONCLUSION: Our results are in accordance with previous studies that
      find an association between night work and breast cancer risk among women.

PMID- 16411052
TI  - The role of GPs in increasing compliance to colorectal cancer screening: a
      randomised controlled trial (Italy).
AB  - AIMS: To assess the effect of the provider (GPs versus hospital) on the
      compliance in returning the faecal occult blood test. To analyse the
      characteristics of the GP associated with high compliance among his
      beneficiaries. METHODS: A questionnaire about screening attitudes was mailed to
      the 1192 GPs working in 13 districts of the Lazio region. We asked the GPs to
      participate in a randomised trial, we sampled 130 GPs and about 1/10 of the GPs'
      50-75 year old beneficiaries (n = 3657) were invited to be screened at the GP
      office and 1/10 (3675) at the nearest gastroenterology centre. RESULTS: 58.5% of
      the GPs completed the questionnaire and 22.7% agreed to participate in the trial.
      The compliance in the GP arm was 50%, in the hospital arm 16% (RR 3.4; 95% CI:
      3.13-3.70). There was a high variability in the compliance obtained by the GPs.
      GPs with more than 25 patients visited/day and those incorrectly recommended
      screening of colorectal cancer obtained a lower compliance (OR 0.74, 95% CI: 0.57
      0.95 and OR 0.76, 95% CI: 0.59-0.97, respectively). CONCLUSIONS: The involvement
      of GPs in colorectal cancer screening can be very effective to enhance the
      compliance, but the effectiveness is dependent on their willingness to be
      involved.

PMID- 16411053
TI  - Results of a union-based smoking cessation intervention for apprentice iron
      workers (United States).
AB  - OBJECTIVE: Blue-collar workers are more likely to smoke, smoke more heavily, and
      have less success in quitting compared to white-collar workers, and this
      occupational gap is growing over time. Effective smoking cessation interventions
      among blue-collar workers are needed to address growing class-based disparities.
      METHODS: We used a pre-post study design to test feasibility and effect size of a
      smoking cessation trial in a union apprenticeship training program for iron
      workers (n = 337). The 4-month intervention drew upon a health promotion-health
      protection model for smoking cessation among blue-collar workers. We conducted
      pairwise analyses to assess pre-post intervention differences in 7-day point
      prevalence smoking abstinence measured 1 month after intervention was completed.
      Additional secondary outcomes, including smoking frequency, intensity, intention
      and self-efficacy to quit, were also assessed. RESULTS: Baseline smoking
      prevalence was 41%. We observed a 19.4% post-intervention quit rate among
      baseline smokers. There were statistically significant positive changes pre- and
      post-intervention in intention to quit smoking, self-efficacy to quit, and a
      reduction in the number of days smoked. Participation in pro-active intervention
      components was associated with a three-fold (OR = 3.0, 1.15, 7.83) increase in
      the likelihood of quitting. Overall, participation in intervention components was
      low. CONCLUSIONS: Labor union apprenticeship programs represent a promising venue
      for smoking cessation interventions, particularly those that draw upon a health
      promotion-health protection model.

PMID- 16411054
TI  - Body mass index and the risk of death following the diagnosis of colorectal
      cancer in postmenopausal women (United States).
AB  - OBJECTIVES: Although overweight body mass is an established risk factor for
      colorectal cancer incidence, few studies have examined the association between
      body mass index (BMI) and mortality after colorectal cancer diagnosis. We
      examined survival in a group of postmenopausal women according to BMI. METHODS:
      Using the Wisconsin Cancer Reporting System we identified and enrolled 633
      postmenopausal women aged 38-74 years who were diagnosed with colorectal cancer
      in 1988-1991. These women were interviewed by telephone; vital status was
      ascertained via Wisconsin death certificates. Cox proportional hazards regression
      was used to estimate multivariate risks of colorectal cancer-specific and all
      cause mortality. RESULTS: Both underweight (BMI <20.0 kg/m2) (Hazard Ratio (HR)
      2.3, 95% Confidence Interval (CI) 1.0-5.4) and obese (BMI > or = 30.0 kg/m2)
      women (HR 2.1, 95% CI 1.1-3.8) were at increased risk of colon cancer death, as
      compared to normal weight women (BMI 20.0-24.9 kg/m2). No association was
      observed for those with rectal cancer. Approximately 50% increases in all-cause
      mortality were observed among underweight and obese women with colorectal cancer.
      Postmenopausal hormone use did not appear to modify these associations.
      CONCLUSIONS: Underweight and obese postmenopausal women with colon cancer were at
      increased risk of death, though comorbidities may partially account for this
      risk.

PMID- 16411055
TI  - A pooled analysis of bladder cancer case-control studies evaluating smoking in
      men and women.
AB  - OBJECTIVE: A recent study suggested that risk of bladder cancer may be higher in
      women than in men who smoked comparable amounts of cigarettes. We pooled primary
      data from 14 case-control studies of bladder cancer from Europe and North America
      and evaluated differences in risk of smoking by gender. METHODS: The pooled
      analysis included 8316 cases (21% women) and 17,406 controls (28% women) aged 30
      79 years. Odds ratios (ORs) and 95% confidence intervals (95% CI) for smoking
      were adjusted for age and study. Exposure-response was evaluated in a stratified
      analysis by gender and by generalized additive models. RESULTS: The odds ratios
      for current smokers compared to nonsmokers were 3.9 (95% CI 3.5-4.3) for males
      and 3.6 (3.1-4.1) for females. In 11 out of 14 studies, ORs were slightly higher
      in men. ORs for current smoking were similar for men (OR = 3.4) and women (OR =
      3.7) in North America, while in Europe men (OR = 5.3) had higher ORs than women
      (OR = 3.9). ORs increased with duration and intensity in both genders and the
      exposure-response patterns were remarkably similar between genders. CONCLUSION:
      These results do not support the hypothesis that women have a higher relative
      risk of smoking-related bladder cancer than men.

PMID- 16411056
TI  - Polymorphisms of the AURKA (STK15/Aurora Kinase) Gene and Breast Cancer Risk
      (United States).
AB  - AURKA is an important protein in the regulation of G2 to M transition during
      mitosis. Due to this regulatory function, it has been hypothesized to be a
      potential cancer susceptibility gene. Two non-synonymous polymorphisms (F31I and
      V57I) have been associated with breast cancer risk in prior studies. We sought to
      confirm these findings in a large case control study nested within a prospective
      cohort, the Nurses' Health Study. Post-menopausal women who were homozygous for
      the 31I and 57V alleles had an increased risk of invasive breast cancer (OR 1.63,
      95% CI 1.08-2.45). We also performed a meta-analysis to summarize the findings of
      this and prior studies of association between the F31I polymorphism and breast
      cancer risk (Summary OR 1.29, 95% CI 1.08-1.53, p-heterogeneity = 0.29). These
      results confirm prior findings that AURKA represents a low penetrance breast
      cancer susceptibility gene.

PMID- 16411057
TI  - Reliability and validity of an assessment of usual phytoestrogen consumption
      (United States).
AB  - OBJECTIVE: To evaluate the reliability and validity of a food-frequency
      questionnaire (FFQ) and database designed to quantify phytoestrogen consumption.
      METHODS: This study included 195 members of the California Teachers Study (CTS)
      cohort who, over a 10-month period, completed four 24-h dietary recalls, a pre-
      and post-study FFQ, and provided two 24-h urine specimens. Participants (n = 106)
      in a parallel study (and 18 women who dropped out of the long-term study)
      completed a single recall and FFQ, and provided one 24-h urine specimen. Urinary
      phytoestrogens were determined using liquid chromatography-mass spectrometry.
      Reliability and validity were evaluated using Shrout-Fleiss intraclass
      correlations and energy-adjusted deattenuated Pearson correlations, respectively.
      RESULTS: Correlations reflecting the reproducibility of the FFQ phytoestrogen
      assessment ranged from 0.67 to 0.81. Validity correlations (FFQ compared to
      dietary recalls) ranged from 0.67 to 0.79 for the major phytoestrogenic compounds
      (i.e., daidzein, genistein, and secoisolariciresinol) and 0.43 to 0.54 for the
      less common compounds. Compared to urinary levels, validity correlations ranged
      from 0.41 to 0.55 for the isoflavones and 0.16 to 0.21 for total lignans.
      CONCLUSION: Our isoflavone assessment is reproducible, valid, and an excellent
      tool for evaluating the relationship with disease risk in non-Asian populations.
      Further research is needed before these tools can accurately be used to assess
      lignan consumption.

PMID- 16411058
TI  - Attitudes Regarding Overweight, Exercise, and Health among Blacks (United
      States).
AB  - OBJECTIVE: To investigate Blacks'views regarding the connections among
      overweight, exercise, and health. METHODS: A national randomized telephone survey
      of 986 US Blacks, conducted between 6 July 2004 and 15 July 2004. RESULTS: The
      majority (65%) of respondents reported their weight as average or underweight.
      Most participants also reported being regularly physically active in the last
      month (84.5%). The majority of participants reported believing that it is
      possible to be overweight and healthy. Most acknowledged the connection between
      exercise and health, and just over half of respondents identified the association
      between overweight and cancer risk. There was little sociodemographic variation
      in responses, although findings differed by self-reported overweight and physical
      activity. CONCLUSIONS: Some Blacks may underestimate the extent of their
      overweight, perhaps resulting from the high prevalence of the condition in the
      population. Gaps exist in Blacks' recognition of the connection between weight
      and health, although the importance of exercise for health promotion was widely
      acknowledged. These data may highlight an important target for intervention
      attention.

PMID- 16411059
TI  - Ultraviolet radiation at places of residence and the development of melanocytic
      nevi in children (Australia).
AB  - OBJECTIVE: To investigate the relationship between ambient ultraviolet radiation
      (UV) exposure and number of melanocytic nevi in children. METHODS: A longitudinal
      study of nevi was conducted in 1614 children in Perth, Australia. Children had
      nevi counted on the back, face and arms at ages 6, 10, and 12 years. Erythemally
      effective UV irradiance was used to estimate ambient exposure from their places
      of residence before entry to the study at age 6 years. Data on UV radiation were
      derived from satellite measurements of ozone and atmospheric reflectivity.
      RESULTS: At baseline, the response rate was 70%. At age 10, 90% of those
      recruited had nevus counts and at age 12, 69%. Children who had migrated to Perth
      from geographical locations with higher erythemal irradiance had, on average,
      1.34 (95% confidence interval, 1.16-1.54) times as many nevi on the back at age
      6, 1.29 (1.13-1.49) as many at age 10 and 1.10 (0.92-1.30) times as many at age
      12. No significant associations were seen for the face or arms. CONCLUSION:
      Ambient solar UV exposure in early childhood is positively associated with number
      of nevi and nevi develop soon after exposure to sunlight.

PMID- 16411060
TI  - Physical activity and risk of ovarian cancer: results from the Netherlands Cohort
      Study (The Netherlands).
AB  - OBJECTIVE: To investigate the association between nonoccupational physical
      activity and the risk of ovarian cancer among post-menopausal women. METHODS: The
      Netherlands Cohort Study on Diet and Cancer consists of 62,573 women aged 55-69
      years at baseline. Information regarding baseline nonoccupational physical
      activity and history of sports activity was collected with a self-administered
      questionnaire in 1986. After 11.3 years of follow-up, 252 cases of invasive
      epithelial ovarian cancer were available for case-cohort analysis. RESULTS: In
      multivariate analysis and compared to women who spent less than 30 min per day on
      physical activity, the rate ratios (RRs) of ovarian cancer for women who spent up
      to 60, 90 and >90 min per day were 0.78, 0.86 and 0.72, respectively (95%
      confidence interval (CI) for the top category, 0.48-1.06; p-trend, 0.15). Women
      who spent more than 2 h per week on recreational biking and walking had a reduced
      risk of ovarian cancer (RR = 0.65; 95% CI: 0.41-1.01) compared to women who never
      participated in recreational biking or walking. CONCLUSIONS: These data suggest a
      modest inverse association between moderate physical activity and ovarian cancer
      risk. Vigorous physical activity was not associated with ovarian cancer risk.

PMID- 16411061
TI  - Polymorphisms in inflammation-related genes and risk of gastric cancer (Finland).
AB  - Helicobacter pylori infection is an important risk factor for gastric cancer, but
      <3% of carriers of this organism will ever develop gastric cancer. Since
      inflammation plays a significant role in gastric carcinogenesis, it has been
      suggested that polymorphisms in genes involved in inflammatory response may
      partly explain why only a subgroup of patients infected with H. pylori develop
      gastric cancer. We compared relative frequencies of 17 single nucleotide
      polymorphisms (SNPs) in eight inflammation-related genes between 112 gastric
      cancer patients and 208 controls. Cases and controls were selected from a large
      cohort of Finnish male smokers who were recruited into the Alpha-Tocopherol, Beta
      Carotene Cancer Prevention (ATBC) Study. The studied SNPs were IL-1A (-889 C/T),
      IL-1B (-511 C/T and -31 T/C), IL-6 (-174 G/C and -597 G/A), IL-8 (-251 T/A, +396
      T/G and +781 C/T), IL-8RA (Ex2 +860 G/C), IL-8RB (Exon 3 +1235 T/C, Exon 3 +811
      C/T, and Exon 3 +1010 G/A), IL-10 (-819 C/T, -592 C/A, -1082 A/G), and TNF A (
      308 G/A, -238 G/A). We found no statistically significant association between any
      of these SNPs, or the number of pro-inflammatory polymorphisms, with risk of
      gastric cancer. Our results do not support the hypothesis that polymorphisms in
      genes involved in the inflammatory response confer differences in gastric cancer
      risk among different individuals.

PMID- 16411062
TI  - The epidemiology of prolactinomas.
AB  - Prolactin-secreting tumors (prolactinomas), the most frequently occurring
      pituitary tumor, have a frequency that varies with age and sex. They occur most
      frequently in females aged 20 to 50 years old, at which time the female-to-male
      ratio is approximately 10:1. In the pediatric-adolescent age group, prolactinomas
      have a prevalence of 100/million population, and account for less than 2% of all
      intracranial tumors. Prolactinomas occur in approximately 30% of patients with
      multiple endocrine neoplasia type 1 and in this setting, they may be more
      aggressive than their sporadic counterparts. Patients with Carney complex or
      McCune-Albright syndrome may exhibit hyperprolactinemia due to a pituitary tumor
      derived from somatomammotropic cells that secrete both growth hormone and
      prolactin. Few familial cases of prolactinoma unrelated to MEN-1 are reported in
      literature.

PMID- 16411063
TI  - Pathogenesis of prolactinomas.
AB  - In recent years the demonstration that human pituitary adenomas are monoclonal in
      origin provides further evidence that pituitary neoplasia arise from the
      replication of a single mutated cell in which growth advantage results from
      either activation of proto-oncogenes or inactivation of tumor suppressor genes.
      However, with the exception of one RAS mutation identified in a single unusually
      aggressive prolactinoma resistant to dopaminergic inhibition that resulted to be
      lethal, no mutational changes have been so far detected in prolactinomas. In the
      absence of genetic changes, modifications in the level of expression of oncogenes
      or tumor suppressor genes have been detected in these tumors, although it is
      unknown whether these changes have a causative role or are a secondary event.
      Indeed, our knowledge on the molecular events involved in lactotroph
      proliferation is even more limited in comparison to the other tumor types, since
      these tumors are very infrequently surgically removed and therefore available for
      molecular biology studies. In this respect, it is worth noting that the molecular
      and biological abnormalities so far described in prolactinomas mainly concern
      aggressive and atypical tumors and likely do not apply to the typical
      prolactinomas, that are characterized by good response to medical treatment and a
      very low growth rate.

PMID- 16411064
TI  - Angiogenesis in prolactinomas: regulation and relationship with tumour behaviour.
AB  - Tumours are dependent on angiogenesis for growth and inhibition of angiogenesis
      has become a target for antineoplastic therapy. In the pituitary, unlike other
      tissues, vascularization is lower in adenomas compared to the normal gland.
      Despite this finding, a relationship between increased vascularity and several
      aspects of prolactinoma behaviour such as size, invasiveness, surgical outcome
      and malignancy, has been demonstrated. The process of angiogenesis is the result
      of a balance of stimulating and inhibiting factors. It is likely that an
      interaction between gene expression (such as pituitary tumour transforming gene
      (PTTG) and a novel gene located within the Edpm5 quantitative trait locus),
      hormonal stimuli including oestrogens, dopamine, 16 kDa fragments of prolactin
      and proangiogenic and antiangiogenic growth factors (for example, vascular
      endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2), determine
      the final angiogenic phenotype of prolactinomas, and thus subsequent tumour
      behaviour. The elucidation of all the factors involved in the regulation of
      angiogenesis and their interactions might open new possibilities in the treatment
      of prolactinomas, especially in those cases with resistance or intolerance to
      dopamine agonists.

PMID- 16411065
TI  - Prolactin and autoimmunity.
AB  - The interrelationship between prolactin (PRL) and the immune system have been
      elucitaded in the last decade, opening new important horizons in the field of the
      immunoendocrinology. PRL is secreted not only by anterior pituitary gland but
      also by many extrapituitary sites including the immune cells. The
      endocrine/paracrine PRL has been shown to stimulate the immune cells by binding
      to PRL receptors. Increased PRL levels, frequently described in autoimmune
      diseases, could depend on the enhancement of coordinated bi-directional
      communications between PRL and the immune system observed in these diseases.
      Hyperprolactinemia has been described in the active phase of some non organ
      specific autoimmune diseases, as systemic lupus erythematosus (SLE) and
      rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac
      disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid
      diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by
      Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody
      production. Of particular interest is the association between hyperprolactinemia
      and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin
      antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies
      (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus,
      in Hashimoto's thyroiditis, in Addison's disease and in celiac disease,
      respectively. High levels of PRL have been also frequently detected in patients
      with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to
      explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the
      inflammatory process of the pituitary gland but, on the other hand, this increase
      could have a role in enhancing the activity of the immune process in LYH.
      Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells
      in some patients with idiopathic hyperprolactinemia suggests the occurrence of a
      possible silent LYH in these patients. Finally, the role of anti-prolactinemic
      drugs to inactivate the immune process in LYH is still discussed.

PMID- 16411066
TI  - Prolactinomas and pregnancy.
AB  - Prolactinomas are the most frequent pituitary tumors. Treatment of infertility in
      such tumors usually is very successful. On the other hand, reports of pituitary
      tumor growth during pregnancy have been described since bromocriptine started to
      be used. Since then, dopamine agonists (DA) have been increasingly used as the
      first-choice treatment of prolactinomas, with surgery being reserved for
      resistance or persistent intolerance to DA or for special situations. More
      recently other DA, such as quinagolide and cabergoline have shown better
      tolerance than bromocriptine with similar or greater efficacy. Cabergoline is now
      the first choice drug but its use in pregnancy is still under evaluation. We
      followed 71 term pregnancies in women bearing microprolactinomas. Of the 22
      patients with previous surgery, none presented symptoms of tumor growth. Of the
      41 pregnant patients treated with bromocriptine alone, only one (2.4%) presented
      with headaches, which regressed with drug reintroduction. Fifty one term
      pregnancies in patients with macroprolactinomas were followed by us. Of those, 21
      were in patients with previous surgery and none of them presented clinical
      evidence of tumor growth. On the other hand, of the 30 patients treated only with
      pre-gestational bromocriptine, 11 (37%) manifested complaints related to tumor
      growth. A non-hormonal contraceptive should be the use along with a DA drug until
      tumor shrinkage within sellar boundaries has been evidenced. After pregnancy has
      been confirmed, the DA can be withdrawn and the patient must be closely followed.
      If tumor expansion is suspected, confirmation can be made through MRI and by
      visual field testing. Reintroduction of bromocriptine in such cases can lead to
      tumor reduction and clinical improvement. Surgery can also be employed as
      treatment for symptomatic tumor growth in pregnancy.

PMID- 16411067
TI  - PRL secreting adenomas in male patients.
AB  - Prolactinomas are the most frequent pituitary tumors and their frequency varies
      with age and sex, occurring most frequently in females between 20-50 yr-old. In
      men, hyperprolactinaemia is often present for many years without symptoms, as
      generally the most important symptoms are the decrease in libido and/or sexual
      potency both underestimated by the majority of the patients. Prolactin (PRL)
      plays a role in the process of spermatogenesis, and normal serum PRL levels are
      required for normal testicular function. On the other hand, hyperprolactinaemia
      has multiple negative effects on the gonadal axis. As a consequences
      hyperprolactinemic males show alteration of sexual potency and seminal fluid
      quality. Cabergoline treatments is able to induce normalization of PRL levels and
      a reduction of tumor mass in the majority of patients and consequently restoring
      the normal semen quality and ameliorating the quality of life of men with
      pituitary PRL-secreting adenoma.

PMID- 16411069
TI  - Surgical outcomes in hyporesponsive prolactinomas: analysis of patients with
      resistance or intolerance to dopamine agonists.
AB  - Surgery for prolactinoma patients is usually reserved for those who are
      intolerant of or have an inadequate response to medication. We report the results
      of surgical treatment in these patients. METHODS: We retrospectively analyzed a
      consecutive series of patients with histopathologically confirmed prolactinomas;
      two patients treated with craniotomy and 77 patients with prolactinomas treated
      by transsphenoidal surgery between 1993 and 2003. We evaluated symptomatic
      patients who did not tolerate or did not respond to dopamine agonist therapy
      (persistent hyperprolactinemia and/or no shrinkage of tumor mass). We report
      remission rates, prolactin levels, and medications either not tolerated or
      ineffective. RESULTS: Eighteen patients were intolerant of medical therapy (nine
      with macroadenomas and nine with microadenomas). Postoperatively, 12 patients
      (67%) achieved normalization of prolactin and relief of symptoms from surgery
      alone. Sixty-one patients were resistant to dopamine agonist therapy (45 with
      macroadenomas and 16 with microadenomas). Forty-six patients had both elevated
      prolactin levels and no shrinkage. 22 patients (36%) achieved normal
      postoperative prolactin levels. Ten of the remaining 39 patients required
      adjunctive medical therapy to maintain normal prolactin levels and relief of
      symptoms. CONCLUSIONS: Remission through surgery was achieved in 67% (12 of 18
      patients, 4 macroadenomas and 8 microadenomas) of prolactinoma patients who fail
      medical therapy with dopamine agonists because of intolerance to medication.
      Remission was also achieved in 36% (22 of 61 patients, 12 macroadenomas and 10
      microadenomas) of patients who demonstrated resistance to dopamine agonist
      medication.

PMID- 16411070
TI  - Combined treatment of invasive giant prolactinomas.
AB  - The management of invasive giant prolactinomas (IGP) has been an area of some
      controversy. The relative roles of transsphenoidal surgery, craniotomy, radiation
      therapy and dopamine agonist based medical therapy are gradually becoming
      clarified. We report the results of management of 30 patients with IGP. Surgery
      was the initial therapy in 18 patients and was nearly always followed by
      adjunctive treatment with radiotherapy and/or bromocriptine. A second group of 12
      patients had initial therapy with bromocriptine; 6 had subsequent radiotherapy
      and only 1 had transsphenoidal surgery. Outcomes with regard to relief of mass
      effect, visual improvement, pituitary function and complications of therapy were
      superior in the bromocriptine treated patients.

PMID- 16411068
TI  - Pharmacologic resistance in prolactinoma patients.
AB  - Pharmacologic resistance to dopamine agonists is defined here as failure to
      normalize PRL levels and failure to decrease macroprolactinoma size by >or=50%.
      Failure to normalize PRL levels is found in about one-quarter of patients treated
      with bromocriptine and 10-15% of those treated with pergolide or cabergoline.
      Failure to achieve at least a 50% reduction in tumor size occurs in about one
      third of those treated with bromocriptine and 10-15% of those treated with
      pergolide or cabergoline. The cause of dopamine resistance is primarily a
      decrease in D(2) receptors but the receptors have normal affinity for dopamine.
      Treatment approaches for patients resistant to dopamine agonists include changing
      to another dopamine agonist and increasing the dose of the drug as long as there
      is continued response to the dose increases and no adverse effects with higher
      doses. Transsphenoidal surgery is also an option. Clomiphene, gonadotropins, and
      GnRH can be used if fertility is desired. For those not desiring fertility,
      estrogen replacement may be used unless there is a macroadenoma, in which case
      control of tumor growth is also an issue and dopamine agonists are generally
      necessary. In many patients modest or even no reduction in tumor size may be
      acceptable as long as there is not tumor growth. Hormone replacement (estrogen or
      testosterone) may cause a decrease in efficacy of the dopamine agonist so that it
      must be carried out cautiously. Reduction of endogenous estrogen, use of
      selective estrogen receptor modulators, and aromatase inhibitors are potential
      experimental approaches.

PMID- 16411071
TI  - Modeling and observer design for recombinant Escherichia coli strain.
AB  - A mathematical model for recombinant bacteria which includes foreign protein
      production is developed. The experimental system consists of an Escherichia Coli
      strain and plasmid pIT34 containing genes for bioluminescence and production of a
      protein, beta-galactosidase. This recombinant strain is constructed to facilitate
      on-line estimation and control in a complex bioprocess. Several batch experiments
      are designed and performed to validate the developed model. The design of a model
      structure, the identification of the model parameters and the estimation problem
      are three parts of a joint design problem. A nonlinear observer is designed and
      an experimental evaluation is performed on a batch fermentation process to
      estimate the substrate consumption.

PMID- 16411072
TI  - Virtual parameter-estimation experiments in Bioprocess-Engineering education.
AB  - Cell growth kinetics and reactor concepts constitute essential knowledge for
      Bioprocess-Engineering students. Traditional learning of these concepts is
      supported by lectures, tutorials, and practicals: ICT offers opportunities for
      improvement. A virtual-experiment environment was developed that supports both
      model-related and experimenting-related learning objectives. Students have to
      design experiments to estimate model parameters: they choose initial conditions
      and 'measure' output variables. The results contain experimental error, which is
      an important constraint for experimental design. Students learn from these
      results and use the new knowledge to re-design their experiment. Within a couple
      of hours, students design and run many experiments that would take weeks in
      reality. Usage was evaluated in two courses with questionnaires and in the final
      exam. The faculties involved in the two courses are convinced that the experiment
      environment supports essential learning objectives well.

PMID- 16411073
TI  - Study of the experimental conditions for the lipase production by a newly
      isolated strain of Pseudomonas aeruginosa for the enantioselective hydrolysis of
      (+/-)-methyl trans-3(4-methoxyphenyl) glycidate.
AB  - A lipase producing bacterium has been isolated from the soil to
      enantiospecifically hydrolyze the (+/-)-methyl trans-3(4-methoxyphenyl) glycidate
      (MPGM), an intermediate in the synthesis of cardiovascular drug, diltiazem. This
      hydrolysis provided the desired (-)-MPGM in 44% yield with 99% enantiomeric
      excess. The organism was identified and confirmed as Pseudomonas aeruginosa by
      16S rRNA sequencing. The various physiochemical parameters have been optimized
      for the maximum production of lipase in shake flask. Beef extract was found to be
      the best nitrogen source for lipase production. The optimized cultivation
      conditions were 30 degrees C with an initial medium pH 8 in shake flask. Both
      inoculum age and inoculum concentration have positive effect on the lipase
      production and (+/-)-MPGM (3 mM) was found to be the optimal inducer.

PMID- 16411074
TI  - [New epidemiology of acute gastrointestinal hemorrhage].
AB  - Due to progress in general medicine and especially in gastroenterology, the
      incidence of acute gastrointestinal hemorrhage could be expected to have
      decreased during the last 25 years. However, published epidemiological data
      cannot, in general, fulfill this hope. The interpretation of potential trends is,
      however, often limited by low study quality. For example, questionable bleeding
      sources such as erosions in the upper gastrointestinal tract or colon diverticula
      are often rather uncritically named the definitive causes of bleeding. However,
      there is clear evidence of changes in grouping of patients. After the almost
      complete disappearance of Helicobacter pylori in younger indigenous populations
      of most industrialized countries, it is mostly elderly comorbid people with
      additional risk factors (NSAID use, low-dose aspirin, anticoagulation) who are
      affected. Not unexpectedly, this group has generally experienced no change in
      incidence and in fact shows a deterioration of prognosis in case of acute
      bleeding.

PMID- 16411076
TI  - [Gastrointestinal bleeding. Diagnostics and therapy by interventional radiology].
AB  - Modern imaging modalities such as (multislice) helical CT allow new diagnostic
      strategies for gastrointestinal hemorrhage. Today, interventional radiology with
      superselective transcatheter embolization or TIPS procedures allow minimally
      invasive therapeutic management which can support or replace surgery. This review
      is a synopsis of the possibilities and relative merits of diagnostic and
      therapeutic radiological procedures for gastrointestinal bleeding. Which of them
      to use should be decided collaboratively by gastroenterologist, surgeon, and
      radiologist depending on local availability, personal experience, and individual
      patient factors.

PMID- 16411075
TI  - [Gastrointestinal bleeding--concepts of surgical therapy in the upper
      gastrointestinal tract].
AB  - Bleeding of the upper gastrointestinal tract is the main symptom of a variety of
      possible conditions and still results in considerable mortality. Endoscopy is the
      first diagnostic modality, enabling rapid therapeutic intervention. In case of
      intractable or relapsing bleeding, surgery is often inevitable. However,
      emergency operations result in significantly higher mortality rates. Therefore
      the option of early elective surgical intervention should be considered for
      patients at increased risk of relapsing bleeding. If bleeding is symptomatic due
      to a complex underlying condition such as hemosuccus pancreaticus or hemobilia,
      angiography is now recognized as the definitive investigation. Angiographic
      hemostasis can be achieved in most cases. Due to the underlying condition,
      surgical management still remains the mainstay in treating these patients. This
      paper reviews surgical strategy in handling upper gastrointestinal bleeding.

PMID- 16411077
TI  - Novel distance-based atom-type topological indices DAI for QSPR/QSAR studies of
      alcohols.
AB  - In this work, we propose a distance-based atom-type topological index (DAI) for
      quantitative structure-property/activity relationship (QSPR/QSAR) studies. The
      newly constructed index, which codes the structural environment of each atom type
      in a molecule, can be calculated simply. These atom-type topological indices,
      along with our recently proposed Lu index, were used to construct QSPR/QSAR
      models for several representative physical properties and biological activities
      of several data sets of alcohols with a range of non-hydrogen atoms by using
      multiple linear regression (MLR) analysis. The efficiency of these indices is
      verified by high quality QSPR models. The results indicate that the combined use
      of Lu and DAI indices promises to be a useful method for QSPR/QSAR analysis of
      complex compounds.

PMID- 16411079
TI  - Structure and bonding of methyl alkali metal molecules.
AB  - We have carried out a theoretical investigation of the methyl alkali metals CH3 M
      with M=Li, Na, K and Rb using density functional theory (DFT) at the BP86/TZ2P
      level. Our purpose is to determine how the structure and thermochemistry (e.g., C
      M bond lengths and strengths) of these organoalkali metal compounds depend on the
      metal atom, and to understand the emerging trends in terms of quantitative Kohn
      Sham molecular orbital (KS-MO) theory. The C-M bond becomes longer and weaker if
      one goes from Li to the more electropositive Rb. Also, the polarity of the C-M
      bond increases along this series but it preserves a strong intrinsic preference
      to homolytic over ionic dissociation in the gas phase. We show that a description
      of the bonding mechanism in terms of a polar C-M electron-pair bond between the
      methyl radical and alkali metal atom is just as natural as an ionic description
      (i.e., in terms of CH3-+M+) and that it provides a straightforward way of
      understanding all observed trends.

PMID- 16411078
TI  - A theoretical model of Aquifex pyrophilus flagellin: implications for its
      thermostability.
AB  - Aquifex pyrophilus is a flagellated hyperthermophilic eubacterial species that
      grows optimally at 85 degrees C. The thermostable A. pyrophilus flagellar
      filament is primarily composed of a single protein called flagellin (FlaA). The N
      and C-terminal sequence regions of FlaA are important for self-assembly and
      share high sequence similarity with mesophilic bacterial flagellins. We have
      developed a predictive 3D-structure of FlaA, using the published structure of
      mesophilic Salmonella typhimurium flagellin (FliC) as a template and analyzed it
      with respect to possible determinants of thermostability. A sequence comparison
      of FlaA and FliC revealed a +7.0% increase in FlaA hydrophobic residues, a +0.6%
      increase in charged residues and a corresponding decrease of -6.0% in polar
      residues. The FlaA N- and C-termini also have higher proportions of hydrophobic
      and charged residues at the expense of polar residues and higher non-polar
      surface areas. Thus, a predominant stabilizing factor in FlaA appears to be
      increased hydrophobicity, which often confers greater rigidity to proteins. Fewer
      intramolecular ion pairs were observed in FlaA than FliC, although an increase in
      the positive charge potential of the FlaA D0 and D1 domains was also observed;
      increased intermolecular salt bridges may also contribute to the thermal
      stability of the oligomeric flagellar fiber. [Figure: see text].

PMID- 16411080
TI  - Chemical carcinogens in non-enzymatic cytosine deamination: 3
      isocyanatoacrylonitrile.
AB  - Uracil has long been known as the main product of nitrosative cytosine
      deamination in aqueous solution. Recent mechanistic studies of cytosinediazonium
      ion suggest that the cation formed by its dediazoniation can ring-open to N
      protonated (Z,s-cis)-3-isocyanatoacrylonitrile 7. Stereochemical preferences are
      discussed of the 3-isocyanatoacrylonitriles (Z,s-cis)-10, (E,s-cis)-11, (Z,s
      trans)-12, and (E,s-trans)-13. The electronic structures of 7 and 10-13 have been
      analyzed and a rationale is provided for the thermodynamic preference for (Z,s
      cis)-10. It is shown that s-cis/s-trans-interconversion occurs via C-N rotation
      inversion paths with barriers below 3 kcal mol(-1). The proton affinities of 3
      isocyanatoacrylonitrile 10 and water are nearly identical and, thus, 3
      isocyanatoacrylonitriles can and should be formed in aqueous media from 7 along
      with 3-aminoacrylonitriles 9. The results highlight the relevance of the
      chemistry of 3-isocyanatoacrylonitriles for the understanding of the chemical
      toxicology of nitrosation of the nucleobase cytosine.

PMID- 16411081
TI  - Does the donor-acceptor concept work for designing synthetic metals? III.
      Theoretical investigation of copolymers between quinoid acceptors and aromatic
      donors.
AB  - Homopolymers of quinoxaline (QX), benzothiadiazole (BT), benzobisthiadiazole
      (BBT), thienopyrazine (TP), thienothiadiazole (TT), and thienopyrazinothiadiazole
      (TTP) and copolymers of these acceptors with thiophene (TH) and pyrrole (PY) were
      investigated with density functional theory. Theoretical band-gap predictions
      reproduce experimental data well. For all but six copolymers, band-gap reductions
      with respect to either homopolymer are obtained. Four of the acceptors, BBT, TP,
      TT, and TTP, give rise to copolymers with band gaps that are smaller than that of
      polyacetylene. BBT and TTP copolymers with PY in 1:2 stoichiometry are predicted
      to be synthetic metals. Band-gap reductions result from upshifts of HOMO energies
      and much smaller upshifts of LUMO values. The smallest band gaps are predicted
      with TTP, since changes in LUMO energies upon copolymerization are particularly
      small. The consequence of the small interactions between LUMO levels of donor and
      acceptor are vanishingly small conduction bandwidths.

PMID- 16411082
TI  - Gene expression of vascular endothelial growth factor-A in the pituitary during
      formation of the vascular system in the hypothalamic-pituitary axis of the rat.
AB  - Techniques involving fluorescein-5-isothiocyanate-conjugated gelatin injection,
      immunohistochemistry, and in situ reverse transcription/polymerase chain reaction
      (RT-PCR) revealed a close relationship between vascular endothelial growth factor
      (VEGF)-A-expressing cells and microvessels in the hypothalamic-pituitary axis of
      the rat. In situ RT-PCR clearly indicated the presence of VEGF-A mRNA-expressing
      cells in the pars tuberalis and in the pars distalis both at embryonic day 15.5
      (E15.5) and in later developmental stages. The primary capillaries extended along
      the developing pars tuberalis, whereas the portal vessels penetrated into the
      pars distalis at E15.5 and subsequently expanded into the lobe to connect with
      the secondary capillary plexus, emerging in the pars distalis. At the same time,
      several VEGF-A-positive cells appeared in the pars distalis. These VEGF-A
      positive cells were found to correspond to a portion of adrenocorticotropin
      (ACTH) cells by dual-staining for in situ RT-PCR and immunohistochemistry,
      suggesting that some ACTH cells have the potential to produce VEGF-A. Thus, the
      present study suggests that VEGF-A is involved in the development of the primary
      capillaries and in the vascularization of the pars distalis, but not in the
      portal vessels since the formation of portal vessels begins at E13.5, before the
      appearance of VEGF-A in the rostral region of the pars distalis.

PMID- 16411085
TI  - Analysis of genetic diversity in Ganoderma population with a novel molecular
      marker SRAP.
AB  - Genetic marker technology designed to detect naturally occurring polymorphisms at
      the DNA level had become an invaluable and revolutionizing tool for both applied
      and basic studies of fungi. To eliminate the confusion on the taxonomy of
      Ganoderma strains, in this study, a collection of 31 accessions representative of
      morphotypes and some unclassified types was used for analyzing molecular
      diversity using a novel molecular marker sequence-related amplified polymorphism
      (SRAP). This collection included commercial cultivars and wild varieties that
      represented the great diversification of types from different countries and
      regions. The experimental results showed that 50 out of 95 combinations of
      primers turned out to be polymorphic, and 85 polymorphism bands were obtained
      using six combinations. Based on the appearances of markers, the genetic
      similarity coefficients were calculated, and genetic variations were observed (0
      approximately 1) among the 31 different Ganoderma strains. The group of Ganoderma
      lucidum showed significant differences from the group of Ganoderma sinense.
      Moreover, G. lucidum in China was also different from G. lucidum in Yugoslavia.
      At the same time, cluster analysis successfully categorized these 31 Ganoderma
      strains into five groups. These results revealed the genetic diversity of
      Ganoderma strains and their correlation with geographic environments. It also
      suggested SRAP marker could be used in the taxonomic analysis of fungi. To our
      knowledge, this is the first application of SRAP marker on the systematics of
      Ganoderma strains within basidiomycetes.

PMID- 16411084
TI  - MR-based coronary artery blood velocity measurements in patients without coronary
      artery disease.
AB  - To evaluate the feasibility of MR-based coronary blood velocity measurements
      (MRvenc) in patients without coronary artery disease (CAD). Eighty-three patients
      with angiographically excluded CAD received MRvenc of the proximal segments of
      both coronary arteries (CAs). Using a retrospectively ECG-gated breath-hold phase
      contrast FLASH sequence with high temporal resolution, flow data were technically
      acquirable in 137/166 (83%) CAs. Quantification and analysis of blood velocities
      in systole and diastole of both CAs were performed. Biphasic velocity profiles
      were found in 83/100 CAs. Median systolic and diastolic velocities differed
      significantly in LCA (19 cm/s, 24 cm/s; P<0.0001) and RCAs (14 cm/s, 16 cm/s;
      P<0.01). The diastolic/systolic velocity ratio was calculated in LCAs and RCAs
      with a median of 1.3 and 1.1, respectively. The velocity profiles of the
      remaining CAs were monophasic (17 CAs) or revealed severe alterations of the
      physiologic velocity profile with reduced flow undulations and steady velocities
      (37 CAs). Optimized clinical MRvenc is feasible to quantify blood velocities in
      the CAs. Potential indications are (1) non-invasive monitoring of patients after
      aortic valve reconstruction as well as (2) detection of asymptomatic CAD
      patients.

PMID- 16411083
TI  - Imaging and diagnostic strategy of soft tissue tumors in children.
AB  - The diagnosis of a soft tissue mass in children is a common clinical situation.
      Most of the lesions are benign and can be treated conservatively or by non
      mutilating surgery. Nevertheless, the possibility of a malignant soft tissue
      tumor must be systematically considered. The most frequent benign soft tissue
      lesions in children are vascular lesions, fibrous and fibrohistiocytic tumors and
      pseudotumors, whereas rhabdomyosarcomas account for 50% of all soft tissue
      sarcomas. A child presenting an atypical soft tissue mass should be managed by a
      multidisciplinary centre, and primary resection must be proscribed until a
      definite diagnosis has been established. The role of imaging is essential either
      to confirm the benign nature of the mass or to give arguments to perform a
      diagnostic biopsy. Clinical examination, conventional radiography and ultrasound
      with Doppler represent the first-line examinations and are sometimes sufficient
      to assess a diagnosis. In all other situations, MRI is mandatory to establish the
      probable nature of the lesion and to assess local extension.

PMID- 16411086
TI  - Characterization of the T7 promoter system for expressing penicillin acylase in
      Escherichia coli.
AB  - The pac gene encoding penicillin acylase (PAC) was overexpressed under the
      regulation of the T7 promoter in Escherichia coli. PAC, with its complex
      formation mechanism, serves as a unique target protein for demonstration of
      several key strategies for enhancing recombinant protein production. The current
      T7 system for pac overexpression was fraught with various technical hurdles. Upon
      the induction with a conventional inducer of isopropyl-beta-D
      thiogalactopyranoside (IPTG), the production of PAC was limited by the
      accumulation of PAC precursors (proPAC) as inclusion bodies and various negative
      cellular responses such as growth inhibition and cell lysis. The expression
      performance could be improved by the coexpression of degP encoding a periplasmic
      protein with protease and chaperone activities. In addition to IPTG, arabinose
      was shown to be another effective inducer. Interestingly, arabinose not only
      induced the current T7 promoter system for pac expression but also facilitated
      the posttranslational processing of proPAC for maturation, resulting in
      significant enhancement for the production of PAC. Glycerol appeared to have an
      effect similar to, but not as significant as, arabinose for enhancing the
      production of PAC. The study highlights the importance of developing suitable
      genetically engineered strains with culture conditions for enhancing recombinant
      protein production in E. coli.

PMID- 16411087
TI  - Fatal varicella infection in a girl with systemic lupus erythematosus after oral
      acyclovir prophylaxis.

PMID- 16411088
TI  - Coumarin embryopathy in an extremely low birth weight infant associated with
      neonatal hepatitis and ocular malformations.
AB  - Coumarin embryopathy (CE) is a well-documented sequelae of prenatal exposure to
      vitamin K antagonists. We report on a female premature infant (25 weeks'
      gestation) born to a mother who had received phenprocoumon during pregnancy
      following mechanical heart valve replacement. The infant presented with impaired
      coagulation, intraventricular and minor parenchymal cerebral haemorrhages and
      midface hypoplasia typical of CE. In addition, there was hepatopathy with
      conjugated hyperbilirubinemia, elevated liver enzymes and repeated episodes of
      hypoglycemia upon attempts to discontinue glucose supplementation, all lasting
      for 4 months. There was corneal opacity with anterior segment dygenesis in the
      left eye, and persistent pupillary membrane, cataract and persistent hyperplastic
      primary vitreous in the right eye. While liver disease is an uncommon but serious
      side effect of vitamin K antagonists, this is the first report describing
      neonatal hepatopathy as part of CE. In anticoagulation of pregnant women with
      mechanical heart valves, vitamin K antagonists should be used with utmost
      restraint.

PMID- 16411089
TI  - An unexpected finding in a child with rectal blood loss using video capsule
      endoscopy.

PMID- 16411090
TI  - Syphilis returns to the suburbs.
AB  - Congenital syphilis is now rare in Australia, particularly in suburban areas. The
      disease is both preventable and treatable, however, missed or late diagnosis can
      lead to catastrophic effects. We report an infant who developed congenital
      syphilis after multiple opportunities for preventing this condition were missed.

PMID- 16411091
TI  - Two cases of hyponatremic-hypertensive syndrome in childhood with renovascular
      hypertension.
AB  - We report two children with renovascular hypertension and fibromuscular
      dysplasia. They initially presented with severe hyponatremia, hypokalemia,
      polyuria, and transient proteinuria. This combination of symptoms is known to
      occur in patients with renovascular and malignant hypertension, and is known as
      hyponatremic-hypertensive syndrome (HHS), although it is considered rare in
      children. Since in both of our patients, the renal arterial stenosis was very
      severely or almost totally occlusive, we could not perform percutaneous
      transluminal renal artery angioplasty, and therefore nephrectomy was the only
      option. A histological study showed partial or complete occlusion with intimal
      hyperplasia and medial fibroplasia of intrarenal arteries such as the
      interlobular arteries. CONCLUSION: Both patients showed rapidly progressive
      renovascular hypertension and loss of function of the affected kidney. In order
      to preserve renal function in such cases, early invasive intervention appears to
      be necessary.

PMID- 16411092
TI  - Calpain-3 mutations in Turkey.
AB  - Autosomal recessive limb-girdle muscular dystrophies (LGMD2s) are a clinically
      and genetically heterogeneous group of disorders, characterized by progressive
      involvement of the proximal limb girdle muscles; the group includes at least 10
      different genetic entities. The calpainopathies (LGMD2A), a subgroup of LGMD2s,
      are estimated to be the most common forms of LGMD2 in all populations so far
      investigated. LGMD2A is usually characterized by symmetrical and selective
      atrophy of pelvic, scapular and trunk muscles and a moderate to gross elevation
      of serum CK. However, the course is highly variable. It is caused by mutations in
      the CAPN3 gene, which encodes for the calpain-3 protein. Until now, 161
      pathogenic mutations have been found in the CAPN3 gene. In the present study,
      through screening of 93 unrelated LGMD2 families, we identified 29 families with
      LGMD2A, 21 (22.6%) of which were identified as having CAPN3 gene mutations. We
      detected six novel (p.K211N, p.D230G, p.Y322H, p.R698S, p.Q738X, c.2257delGinsAA)
      and nine previously reported mutations (c.550delA, c.19_23del, c.1746-20C>G,
      p.R49H, p.R490Q, p.Y336N, p.A702V, p.Y537X, p.R541Q) in the CAPN3 gene. There may
      be a wide variety of mutations, but clustering of specific mutations (c.550delA:
      40%, p.R490Q: 10%) could be used in the diagnostic scheme in Turkey.

PMID- 16411093
TI  - Exclusion/confirmation of ataxia-telangiectasia via cell-cycle testing.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder with
      increased radiosensitivity and cancer susceptibility. The responsible gene (ATM)
      consists of 66 exons and a coding region of 9171 bp which precludes direct
      sequencing as a screening assay for confirmation or exclusion of the clinical
      suspicion of AT. Peripheral blood mononuclear cells of 330 patients referred for
      the exclusion of AT were exposed to ionizing radiation (IR) and incubated for 72
      h in the presence of phytohemagglutinin. Using bivariate BrdU-Hoechst/ethidium
      bromide flowcytometry, the following cell cycle parameters were ascertained: (1)
      proportion of non-proliferating (G0,G1) cells as a measure of mitogen response,
      (2) proportion of first-cycle G2-phase cells relative to the growth fraction
      (G2/GF) as a measure of radiosensitivity. Of the cases tested, 94.2% could be
      unequivocally assigned either to the AT-negative or the AT-positive group of
      patients. Of the AT-positive cases, 11 were confirmed by ATM mutation analysis.
      Nineteen cases presented with non-conclusive results, mostly due to poor mitogen
      response; however, a combination of cell-cycle data with serum AFP concentrations
      led to the exclusion of AT in all but two of the uncertain cases. Substitution of
      ionizing radiation by the radiomimetic bleomycin was additionally tested in a
      small series of patients. We conclude that cell-cycle testing complemented by
      serum AFP measurements fulfills the criteria as a rapid and economical screening
      procedure for the differential diagnosis of juvenile ataxias.

PMID- 16411095
TI  - Lichen striatus: clinical and epidemiological review of 23 cases.

PMID- 16411094
TI  - Time trends and prognostic factors for survival from childhood cancer: a report
      from the Childhood Cancer Registry of Piedmont (Italy).
AB  - Survival after childhood cancer has been improving since the late 1970s in most
      developed countries. The Childhood Cancer Registry of Piedmont has been recording
      malignant tumors in children (0-14 years) throughout Piedmont since 1967. The
      present paper is based on the records of the 2,970 children diagnosed during the
      period 1970-2001; survival rates are estimated up to June 30, 2004. Based on
      records from the Registrar Offices of the relevant towns of residence, 1,698
      children were reported to be alive, 1,252 deceased, and 20 were of unknown vital
      status. Over the period 1970-2001, 5-year survival rates for all tumor types
      combined showed a statistically significant increasing trend (p<0.0001). For
      acute lymphocytic leukemia, the survival rate increased steadily from 24.7% (95%
      CI 15.0-34.3) in 1970-1974 to 87.8% (82.1-93.6) in 1995-1999. Five-year survival
      rates for central nervous system tumors increased from 32.8% (21.0-44.6) in 1970
      1974 to 80.3% (72.6-88.0) in 1990-1994 and decreased thereafter. Age of less than
      1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma
      and ganglioneuroblastoma. The extent of disease at diagnosis was related to
      prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid
      tumors. A white blood cell count greater than 50,000 x 10(6) cells/l was
      associated with decreased survival in children with acute lymphocytic leukemia
      and acute non-lymphocytic leukemia. We have found positive trends in survival for
      all tumor types in Piedmont, similar to those reported by other population-based
      cancer registries. Age, extent of disease, and white blood cell count at
      diagnosis are prognostic factors for selected cancer sites.

PMID- 16411096
TI  - Choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To evaluate quantitative choroidal dye filling velocity in patients with
      Vogt-Koyanagi-Harada disease (VKH) before and after corticosteroid treatment
      using indocyanine green (ICG) angiography. METHODS: ICG angiography was performed
      in seven VKH patients before and after systemic corticosteroid treatment.
      Choroidal dye curves were obtained by image analysis software and analyzed using
      an exponential model. The model's time constant (tau) was used to evaluate
      choroidal dye filling velocity. RESULTS: Compared with controls, acute phase
      choroidal tau values in VKH patients were significantly longer, suggesting
      choroidal circulation disturbance. During the recovery phase, choroidal tau
      values were significantly shortened, suggesting choroidal circulatory disturbance
      improvement. CONCLUSION: Choroidal dye filling velocity may be useful for VKH
      diagnosis and verification of corticosteroid treatment effectiveness.

PMID- 16411097
TI  - Detecting vitreomacular adhesions in eyes with asteroid hyalosis with
      triamcinolone acetonide.
AB  - BACKGROUND: To report the incidence of posterior vitreous detachments (PVDs) and
      the surgical results of vitrectomy with intravitreal triamcinolone acetonide (TA)
      to detect vitreomacular adhesions in eyes with asteroid hyalosis (AH). METHODS:
      Ten eyes of nine patients with AH underwent vitrectomy, six eyes with TA and four
      without TA. The presence of a PVD was determined preoperatively by ultrasound
      echography (USE) and intraoperatively by microscopic observations. The
      postoperative best-corrected visual acuities (BCVA) were evaluated. RESULTS: The
      BCVA was improved by >2 Snellen lines in nine eyes and maintained at 20/20 with
      symptomatic improvements in the other eye. A vitreomacular adhesion was clearly
      seen during TA-assisted vitrectomy, and none was seen when TA was not used, even
      though preoperative USE showed an incomplete PVD in all eyes. The BCVA was not
      significantly better in eyes with TA-assisted vitrectomy than without TA-assisted
      vitrectomy. In one eye with vitrectomy without TA, a second surgery was required
      for a persistent cystoid macular edema and an epiretinal membrane. The BCVA and
      the edema in this eye improved after removing the epiretinal membrane.
      CONCLUSIONS: All (ten) of the eyes with AH were found to have a vitreomacular
      adhesion by preoperative USE and intraoperative microscopic observations. The
      residual vitreous over the macula is more easily detected and removed after
      intravitreally injected TA, but the visual acuities were not significantly
      different from eyes without TA.

PMID- 16411098
TI  - Acute retinal necrosis diagnosed in a child with chronic panuveitis.
AB  - BACKGROUND: To report the case of an immunocompetent child with herpes simplex
      virus-2 (HSV-2) acute retinal necrosis (ARN) syndrome, who was considered to have
      an idiopathic unilateral panuveitis sensitive to steroid treatment. METHODS:
      Polymerase chain reaction for detection of viral DNA was applied to ocular fluids
      and in situ hybridization was performed on a retinal sample. HSV serology was
      performed using the ELISA and Western blot techniques, and an in-house indirect
      immunofluorescence technique. RESULTS: In addition to the atypical clinical
      presentation, the serological assays for HSV were negative using ELISA at the
      time of diagnosis of ARN and 1 year after. HSV2 infection was confirmed by using
      polymerase chain reaction of aqueous humor specimen and in situ hybridization of
      a retinal biopsy. Retrospective analysis with the Western blot technique detected
      low titers of anti-HSV antibodies, when the sera were concentrated 5-fold.
      CONCLUSION: Herpes virus infections must be investigated in children with
      posterior or panuveitis. PCR analysis is a reliable technique for diagnosis. This
      case emphasizes that clinical presentation can be atypical and that a negative
      viral serology does not exclude an acute or a past herpetic infection.

PMID- 16411099
TI  - Bilateral nanophthalmos and pigmentary retinal dystrophy--an unusual syndrome.
AB  - BACKGROUND: To report the clinical picture of the rare association of
      nanophthalmos and pigmentary retinal dystrophy and its cataract surgery outcome.
      METHODS: We report a case of a 60-year-old female who presented with bilateral
      slowly progressive visual loss. RESULTS: The patient presented with bilateral
      light perception visual acuity, exotropia, brunescent cataract hindering fundus
      examination and hypodontia. Ultrasonography revealed bilateral nanophthalmos. A
      visual-evoked potential was also performed preoperatively. Cataract surgery with
      +40D IOL implantation was uneventful. Postoperative fundus examination revealed
      pigmentary retinal dystrophy, confirmed by electrophysiologic tests.
      Glycosaminoglycan urinary excretion was normal. CONCLUSIONS: Congenital bilateral
      nanophthalmos may rarely be associated with pigmentary retinal dystrophy. We
      suggest thorough preoperative evaluation in nanophthalmic eyes for the exclusion
      of significant features concerning visual prognosis.

PMID- 16411100
TI  - Asymmetric visual field loss and retrobulbar haemodynamics in primary open-angle
      glaucoma.
AB  - PURPOSE: To investigate interocular differences in retrobulbar flow velocities in
      patients with asymmetric glaucomatous visual field loss. METHODS: Twenty-five
      patients with primary open-angle glaucoma (POAG) and asymmetric visual field loss
      were included in this study. Asymmetric visual field loss was defined as a
      difference of the global index mean deviation (MD) >6 dB between the two eyes.
      Flow velocities (peak systolic velocity PSV and end-diastolic velocity EDV) and
      resistive indices (RI) of the ophthalmic artery (OA), central retinal artery
      (CRA), and nasal and temporal posterior ciliary arteries were measured by means
      of colour Doppler imaging. RESULTS: MD of eyes with more severe glaucomatous
      visual field loss was -18.3+/-7.8 dB vs -6.8+/-5.5 dB (p<0.0001) in the less
      affected eyes. The PSV and the EDV of the CRA and the PSV of the OA were
      significantly decreased in eyes with more severe glaucomatous visual field loss
      (CRA PSV: 7.6+/-2.0 cm/s vs 8.3+/-1.7 cm/s, p=0.04; CRA EDV: 2.24+/-0.5 cm/s vs
      2.55+/-0.6 cm/s, p<0.007; OA PSV: 29.7+/-9.9 cm/s vs 32.7+/-11.5 cm/s, p<0.02).
      None of the other differences in velocity or resistive index were significant.
      CONCLUSIONS: Patients with asymmetric glaucomatous visual field loss exhibit
      asymmetric flow velocities of the CRA and OA. Patients with more severe damage
      display reduced flow velocities in retrobulbar vessels in POAG.

PMID- 16411101
TI  - Three-month change in cerebral glucose metabolism in patients with nonarteritic
      ischemic optic neuropathy.
AB  - BACKGROUND: No specific therapy is available for non-arteritic ischemic optic
      neuropathy (NAION), a blinding disease, which is related to microvascular
      insufficiency of the optic disc and white matter lesions in brain MRI
      representing ischemia. We hypothesize that pentoxifylline, traditionally used for
      treatment of peripheral vascular disease due to its ability to decrease viscosity
      and increase erythrocyte flexibility, may be useful to improve blood flow in
      patients with NAION. Positron emission tomography (PET) to determine the change
      in glucose metabolic rate in the visual cortex of patients with NAION versus age
      matched controls was performed after 3 months' administration of pentoxifylline.
      METHODS: Eight patients clinically diagnosed with NAION underwent clinical and
      laboratory evaluation, brain MRI and PET with fluoride-18 fluorodeoxyglucose
      (FDG). All patients were treated with oral pentoxifylline 400 mg three times a
      day for a period of at least 3 months. Three patients were included in the final
      PET data analysis. RESULTS: At baseline, PET revealed bilateral metabolic
      decreases especially in the ventral visual stream in all patients compared with
      56 age- and gender-normalized controls. Metabolic changes were seen in the dorsal
      stream areas 17, 18, and 19, cerebellar region, dorsolateral prefrontal cortex,
      medial temporal lobe, and frontal eye fields 8 and 6. At 3 months following
      pentoxifylline, all three patients included in the final PET data analysis showed
      partial normalization from the baseline metabolism. CONCLUSIONS: Metabolic
      imaging with FDG-PET in NAION provides functional information not attainable with
      conventional brain MRI. The exact relevance of these results, and the role of
      pentoxifylline in these metabolic changes, should be determined by means of a
      larger randomized and controlled trial.

PMID- 16411102
TI  - Topical diclofenac for the treatment of eyeache in Miller-Fisher syndrome.

PMID- 16411103
TI  - Influence of photodynamic therapy for age related macular degeneration upon
      subjective vision related quality of life.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been used in the treatment of
      choroidal neovascularisation secondary to age-related macular degeneration (AMD).
      This study prospectively investigated patients' subjective change in visual
      function following PDT as treatment for AMD. METHODS: Eighty-two consecutive
      patients receiving PDT in Tasmania, Australia, between May and November 2003 were
      recruited. In conjunction with a comprehensive clinical examination, the Visual
      Function-14 (VF-14) questionnaire was administered. Final follow-up occurred
      between February and March 2005. The VF-14 was scored by traditional summary
      scoring and by Rasch analysis. RESULTS: Five of the 82 (6.1%) subjects recruited
      were excluded from analysis. PDT was performed on average 5.7+/-2.6 times per
      patient. Raw VF-14 scores tended towards being significantly lower at follow-up
      than at baseline (67.6+/-27.2 against 64.5+/-27.7; P=0.052), and did
      significantly deteriorate using a collapsed Rasch analysis (P=0.0102). Following
      treatment, 38 (47.5%) eyes had lost three or more Snellen lines of best-corrected
      visual acuity. CONCLUSION: Patients undergoing PDT typically report reasonable
      visual function. In parallel with visual acuity, self-reported visual function
      may deteriorate slightly after PDT for AMD, but not as much as reported in
      untreated AMD.

PMID- 16411104
TI  - Neuroprotective effect of latanoprost on rat retinal ganglion cells.
AB  - BACKGROUND: To investigate the neuroprotective effect of intravitreal
      administration of latanoprost on retinal ganglion cell (RGC) damage induced by N
      methyl-D-aspartic acid (NMDA) or optic nerve axotomy. METHODS: Using Sprague
      Dawley rats, retinal ganglion cell damage was induced by either intravitreal
      administration of NMDA or optic nerve axotomy. Latanoprost at doses of 0.03, 0.3,
      3, 30 and 300 pmol was administered intravitreally before NMDA injection or optic
      nerve axotomy. Retinal damage was evaluated by counting the number of surviving
      RGCs retrogradely labeled with fluorogold under the microscope. RESULTS: Seven
      days after the NMDA injury, the number of surviving RGCs was significantly
      increased at doses of more than 30 pmol atanoprost (846+/-178 cells/mm(2 )
      P=0.0166) compared with vehicle control (556+/-122 cells/mm(2)). Ten days after
      the optic nerve axotomy, the number of surviving RGC was significantly increased
      even at a dose of 0.3 pmol (815+/-239 cells/mm(2), P=0.0359) compared with
      control (462+/-75 cells/mm(2)). CONCLUSIONS: Intravitreal administration of
      latanoprost has a neuroprotective effect on rat RGC damage induced by either NMDA
      or optic nerve axotomy, while its pharmacological features are different.

PMID- 16411105
TI  - Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of
      oral doxycycline.
AB  - BACKGROUND: Ocular rosacea (OcR) is a chronic inflammatory disease especially
      affecting lid margins. Previous studies have shown that it is accompanied by
      increased levels and activation of tear fluid gelatinases. Matrix
      metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly
      elevated in many inflammatory conditions. Therefore we studied here whether MMP-8
      concentration and activation in tear fluid are increased also in OcR, and if an
      oral doxycycline regimen could rectify the situation. METHODS: Tear fluid samples
      were collected from 22 OcR patients and 22 healthy controls. The OcR patients
      were then treated with an oral doxycycline regimen for 8 weeks and tear fluid
      samples collected again after 4 and 8 weeks. Conjunctival brush cytology and
      patients' subjective symptoms were scored. MMP-8 concentrations in the tear fluid
      were assessed by immunofluorometric assay and the molecular forms and isoenzyme
      expression of MMP-8 were studied by Western immunoblotting. RESULTS: The mean MMP
      8 concentration was statistically significantly higher in OcR (156.8+/-207.4
      mug/ml) than in the normal subjects (53.5+/-66.7 mug/ml) (P=0.036), but decreased
      to 79.2+/-141.6 mug/l and 53.6+/-75.2 mug/l after 4 and 8 weeks doxycycline
      treatment, respectively. There was a statistically significant difference between
      the untreated OcR and the MMP-8 results after 4 or 8 weeks of oral doxycycline
      (P=0.041 and 0.069, respectively) and the OcR patients experienced statistically
      significant relief of their subjective symptoms (P=0.0001) after the doxycycline
      regimen. Both the normal and OcR tear fluid contained the larger, 60-80 kDa
      highly- glycosylated polymorphonuclear leukocyte-type MMP-8 isoform in Western
      immunoblotting, but not the 45-55 kDa less glycosylated mesenchymal-type isoform.
      MMP-8 activation was in practice present only in the OcR samples, and was
      inhibited by oral doxycycline. CONCLUSIONS: MMP-8 concentration and activation
      degree in tear fluid are increased in OcR, probably reflecting increased
      inflammatory activity. Doxycycline effectively reduces these pathologically
      excessive levels and activation of MMP-8, and relieves patients' subjective
      symptoms.

PMID- 16411106
TI  - Association between systemic arterial stiffness and age-related macular
      degeneration.
AB  - BACKGROUND: A number of epidemiological studies suggest that age-related macular
      degeneration (AMD) and cardiovascular disease share the same risk factors.
      Systemic arterial stiffness is a clear indicator of cardiovascular disease. We
      investigated whether there is an association between directly measured systemic
      arterial stiffness and the presence of AMD. METHODS: We used a SphygmoCor 2000
      system to noninvasively measure two indicators of the systemic arterial
      stiffness, the arterial pulse wave velocity (PWV) and the central aortic blood
      pressure waveform, from which the augmentation pressure is determined. We studied
      50 patients with AMD (12 men, 38 women, aged 60 to 91 years, mean 77 years) and
      11 age-matched control subjects (3 men, 8 women, aged 66 to 92 years, mean 75
      years). All study subjects received a complete ophthalmic examination including
      digital fundus photography. All of the patients with AMD were classified as stage
      3 or worse in at least one eye according to the AREDS system. RESULTS: Pulse wave
      velocity was significantly higher in the patients with AMD (8.2+/-1.1 m/s, mean
      +/- SD) compared with controls (7.1+/-0.8 m/s, p=0.0025), indicating increased
      arterial stiffness. There was no significant difference in PWV in AMD patients
      with and without choroidal neovascularization. There was no association between
      PWV and the presence of hypertension in either the patients or the controls. The
      central aortic augmentation pressure was significantly higher in the AMD patients
      than in the controls (p=0.040), also indicating increased arterial stiffness.
      CONCLUSIONS: Patients with AMD have increased systemic arterial stiffness
      compared with age-matched controls. Treatments aimed at preventing or reversing
      systemic arterial stiffness may also be effective in preventing the onset or
      slowing the progression of AMD.

PMID- 16411108
TI  - The effects of interocular differences in retinal illuminance on vision and
      binocularity.
AB  - BACKGROUND: It is known that binocular function is affected by interocular
      differences in retinal image size, shape, clarity, and illumination. The present
      study was performed to systematically examine the effects of interocular
      differences in retinal illuminance on monocular visual acuity, fusion, and
      stereopsis. METHODS: Fifty adults with normal binocularity and a best-corrected
      visual acuity of 20/20 or better were enrolled. We examined best-corrected visual
      acuity, fusion, and stereoacuity as monocular retinal illuminance was gradually
      reduced by increasing neutral density filters from 0.2 neutral density (ND; 63%
      transmission) to 3.0 ND (0.1% transmission) in increments of 0.2 ND. We measured
      the smallest size of fusion slide by major amblyoscope, and evaluated
      stereoacuity with the Titmus test and the Lang test. RESULTS: The best-corrected
      visual acuity began to decrease significantly when the value of the neutral
      density filter reached 2.0 ND (1% transmission; p<0.01). The level of fusion
      decreased significantly when monocular retinal illuminance was reduced to 2.0 ND
      (p<0.01). Stereoacuity began to decline significantly when the value of the
      neutral density filter was 1.4 ND (4% transmission) with the Titmus test and 1.6
      ND (2.5% transmission) with the Lang test. CONCLUSIONS: A binocularly conducted
      Titmus test was the most sensitive to the presence of monocularly induced retinal
      illuminance deterioration.

PMID- 16411107
TI  - Paraoxonase 1 gene polymorphisms influence clinical features of open-angle
      glaucoma.
AB  - BACKGROUND: The purpose of this study was to determine whether genetic
      polymorphisms affecting high-density lipoprotein (HDL)-associated antioxidant
      enzymes were associated with open-angle glaucoma (OAG). The rationale for this
      study was that the modification of low-density lipoprotein (LDL) by HDL prevents
      oxidative modification which can then cause dysfunction of endothelial cells.
      METHODS: We studied 284 normal Japanese controls and 555 Japanese patients with
      OAG, including primary open-angle glaucoma (POAG) and normal-tension glaucoma
      (NTG). The possible associations of polymorphisms of PON1/L55M, PON1/Q192R,
      PON2/S311C, and PAF-AH/V279F with OAG were investigated. We compared the genotype
      distributions and allele frequency in controls and patient groups. The age at
      diagnosis, intraocular pressure (IOP) at diagnosis, and visual field score at
      diagnosis were examined for association with polymorphisms. RESULTS: The
      distributions of genotypes and allele frequency for the four polymorphisms were
      not significantly different between any patient group and controls. In NTG
      patients, 55M carriers of the PON1 gene were significantly older at diagnosis
      than 55M non-carriers (P=0.001). The IOP at diagnosis was significantly higher in
      glaucoma patients carrying 192R in the PON1 gene than in patients not carrying
      192R (P=0.006). No significant differences were seen in clinical characteristics
      of OAG patients in relation to other polymorphisms. CONCLUSION: PON1 gene
      polymorphisms may influence the features of Japanese patients with OAG.

PMID- 16411110
TI  - Ocular infection secondary to gemella.
AB  - PURPOSE: To report four cases of ocular infection caused by Gemella species.
      METHODS: Microbial identification was carried out using the MicroScan Walkaway
      system (Dade Behring) and/or Vitek-2 (bioMerieux) and susceptibility testing with
      either Kirby-Bauer disc diffusion and/or Vitek-2. The paper is presented as an
      interventional case report. RESULTS: Four patients developed infection due to
      Gemella species. All responded to vancomycin or fortified aminoglycosides and
      broad-spectrum antibiotics. CONCLUSION: Gemella spp. can cause opportunistic
      infections in the eye.

PMID- 16411109
TI  - Transpupillary thermotherapy for chronic central serous chorioretinopathy.
AB  - PURPOSE: To determine whether transpupillary thermotherapy (TTT) causes
      resolution of neurosensory detachment associated with chronic central serous
      chorioretinopathy (CSCR). METHODS: The study was a prospective interventional
      pilot study. All patients underwent Snellen visual acuity measurement (converted
      to LogMAR for analysis), slitlamp biomicroscopy, fundus examination, colour
      fundus photography, fluorescein and indocyanine green (ICG) angiography and
      optical coherence tomography (OCT). Follow-up was scheduled at 1, 2 and 3 months.
      Success was defined as resolution of neurosensory detachment on OCT at 3 months,
      and failure as persistence of the same. The primary outcome measure was
      resolution of OCT-measured neurosensory detachment and secondary outcome measure
      was change in visual acuity at the end of 3 months. RESULTS: Fourteen eyes of 13
      patients were included in the study. Twelve patients were male. The left eye was
      affected in seven of 14 eyes. The patients' mean age was 42.7+/-4.5 years (range
      38-54 years). TTT parameters were as follows: power 156+/-47.8 mW; spot size
      2.2+/-1.1 mm; duration 39.6+/-7.5 s. Following treatment, complete resolution of
      neurosensory detachment on OCT was seen in nine eyes (64.3%) at month 1 (P=0.004)
      and 11 eyes (78.6%) at months 2 and 3 (P=0.001). Three eyes (21.4%) had
      persistent subretinal fluid at month 3. Eight eyes (52.7%) had >or=3 lines of
      improvement (two eyes: five lines and six eyes three lines) at the final visit.
      CONCLUSION: Transpupillary thermotherapy could be a therapeutic option in
      patients with chronic CSCR.

PMID- 16411111
TI  - Urinary retention during sacral nerve stimulation for faecal incontinence: report
      of a case.
AB  - Sacral nerve stimulation (SNS) was proposed for the treatment of patients with
      urologic symptoms in 1967 but was not used until 1981. SNS has also proven to be
      a promising treatment in idiopathic faecal incontinence when conventional
      treatments have failed. The modality has been used for faecal incontinence since
      the mid-1990s. Eighty percent of the patients who were selected for percutaneous
      nerve evaluation (PNE) because of faecal incontinence report an improvement in
      the symptoms and qualify for a permanent implantation. Accordingly, SNS is now
      used for faecal incontinence and urologic symptoms. Reflex interactions between
      the bladder and the distal gastrointestinal tract are well known. The present
      case shows that SNS for faecal incontinence may significantly influence bladder
      function.

PMID- 16411112
TI  - Ileus secondary to wireless capsule enteroscopy.
AB  - Wireless capsule enteroscopy, being a novel, painless investigative technique, is
      reported to be significantly superior to push enteroscopy in its ability to find
      bleeding abnormalities in the small intestine. Here we report a case of acute
      jejunal obstruction following wireless capsule endoscopy. The patient had a 1
      month history of gastrointestinal bleeding of unknown source. Further evaluation
      including gastroscopy and colonoscopy, angiography and computed tomography (angio
      CT), and radio-labeled erythrocytes scan failed to reveal a source of bleeding.
      Therefore, wireless capsule enteroscopy was performed. Before capsule endoscopy,
      there was no clinical or imaging evidence of strictures or stenosis. At
      readmission it could be shown that there were two inflamed strictures of the
      small intestine. The capsule was detected at a stricture of the small intestine
      detected by abdominal ultrasonography and conventional computed tomography. The
      patient underwent a medical treatment with steroidal and other anti-inflammatory
      drugs for a total of 23 days and was discharged without complaints. Acute
      laparotomy after readmission with jejunal ileus proofed the capsule occluding two
      highly inflamed jejunal stenosis caused by Crohn disease. The present case
      demonstrates the potential for complications when wireless capsule enteroscopy is
      performed in the presence of intestinal strictures. Any history of inflammatory
      bowel disease, abdominal irradiation, cancer, obstruction, and abdominal surgery
      must be elicited in detail and may exclude the use of wireless capsule
      enteroscopy.

PMID- 16411113
TI  - What is the impact of resistance to activated protein C (Leiden mutation to
      factor V) in inflammatory bowel disease?
AB  - BACKGROUND AND AIMS: Resistance to activated protein C (APCR) caused by the
      Leiden mutation to factor V is the most common cause of inherited thrombosis.
      Patients with inflammatory bowel disease (IBD) are considered to have an
      increased risk of thromboembolic complications, and the role of APCR as a cause
      has previously been investigated. In this study, we investigated if APCR was
      associated with non-thrombotic morbidities in IBD. PATIENTS/METHODS: Of 951
      patients asked to participate, 389 agreed by returning a signed informed consent
      and filled questionnaire and took the blood test for APCR. Self-reported IBD
      related surgery was used as a rough indicator for increased morbidity. RESULTS:
      APCR was present in 6.6% of patients with Crohn's disease (CD; 10/152) and in
      12.7% of ulcerative colitis (UC) patients (30/237). The difference of 6.1% is
      significant (p=0.039). Among patients with CD and APCR, 9 out of 10 had had
      surgery, significantly more than among those without APCR (81/142). In patients
      with UC and APCR, 10 out of 30 had had surgery, still significantly more than in
      those without APCR (36/207). For the whole group of IBD patients, APCR is
      associated with a significantly increased risk for thrombosis (p=0.0018), and for
      the UC group (8/28) p=0.0029, but not for the CD patients alone (2/9), p=0.2323.
      No other significant differences could be shown for parameters normally related
      to increased morbidity. CONCLUSIONS: APCR in IBD was associated with an increased
      frequency of IBD-related surgery, which may warrant screening for APCR in therapy
      resistant IBD. In patients with APCR, it may be more difficult and/or important
      to control inflammation.

PMID- 16411114
TI  - Stapled transanal rectal resection to treat obstructed defecation caused by
      rectal intussusception and rectocele.

PMID- 16411115
TI  - Study of the role of the transverse perineal muscles during rectal filling.
AB  - BACKGROUND: The function of perineal muscles at defecation is poorly addressed in
      the literature. We investigated the hypothesis that rectal distension effects
      reflex contraction of four perineal muscles. PATIENT/METHODS: After rectal
      balloon distension with carbon dioxide in increments of 20 ml, the responses of
      electromyographic (EMG) activity of superficial (STPM) and deep (DTPM) transverse
      perineal muscles as well as the rectal pressure were recorded in 22 healthy
      volunteers (14 men, age 37.2+/-6.3 years). Responses were registered again after
      individual anesthetization of rectum and transverse perineal muscles. Tests were
      repeated using saline instead of lidocaine. RESULTS/FINDINGS: Rectal balloon
      distension in big volumes effected increase of the transverse perineal muscles'
      EMG activity and rectal pressure. The more the rectum was distended, the more the
      rectal pressure and EMG activity of the transverse perineal muscles were
      increased. The latency showed a gradual decrease upon incremental rectal
      distension increase. Transverse perineal muscles did not respond to rectal
      distension after the rectum and perineal muscles had been individually
      anesthetized, but it responded to saline administration. Response of the muscles
      was similar in both sides. INTERPRETATION/CONCLUSION: Increase of rectal pressure
      increases EMG activity of transverse perineal muscles. This action seems mediated
      through a reflex which we call 'recto-perineal reflex'. Contraction of transverse
      perineal muscles at defecation presumably supports the perineal floor. It also
      protects transverse perineal muscles against straining-produced high pressure
      that is transmitted through the recto-vaginal/-vesical cul de sac to the perineum
      which may sag down and share in genesis of perineocele, enterocele, or
      sigmoidocele.

PMID- 16411116
TI  - Perceptual centering effects in body orientation.
AB  - This study mathematically characterizes the results of DiZio and Lackner (Percept
      Psychphys 39(1): 39-46) on the perception of self-orientation during circular
      vection induced by an optokinetic stimulus. Using the hypothesis of perceptual
      centering, it is shown that five basic centering transformations can logically
      account for the full range of illusions reported by the subjects. All five of
      these transformations center the perceived orientations of body components, the
      rotating disk, and gravity : two align the perceived visual and inertial rotation
      axes, one centers the perceived axis of visual rotation in front of the head, and
      two straighten the perceived neck angle. These transformations generate a
      mathematical semigroup. Application of the semigroup to an actual stimulus
      condition generates an orbit of predicted illusions. The semigroup analysis of
      perceptual centering predicts all of the illusions observed in the experiments of
      DiZio and Lackner (Percept Psychphys 39(1): 39-46). Moreover, the structure of
      perceptual centering (1) provides a logical explanation for the occurrence of
      those misperceptions; and (2) predicts the complete set of perceptions that are
      expected to occur in a larger sample. In addition, our analysis predicts
      illusions in experimental conditions not yet investigated.

PMID- 16411117
TI  - Mannose 6-phosphate receptors in an ancient vertebrate, zebrafish.
AB  - The endosome/lysosome system plays key roles in embryonic development, but
      difficulties posed by inaccessible mammalian embryos have hampered detailed
      studies. The accessible, transparent embryos of Danio rerio, together with the
      genetic and experimental approaches possible with this organism, provide many
      advantages over rodents. In mammals, mannose 6-phosphate receptors (MPRs) target
      acid hydrolases to endosomes and lysosomes, but nothing is known of acid
      hydrolase targeting in zebrafish. Here, we describe the sequence of the zebrafish
      cation-dependent MPR (CD-MPR) and cation-independent MPR (CI-MPR), and compare
      them with their mammalian orthologs. We show that all residues critical for
      mannose 6-phosphate (M6P) recognition are present in the extracellular domains of
      the zebrafish receptors, and that trafficking signals in the cytoplasmic tails
      are also conserved. This suggests that the teleost receptors possess M6P binding
      sites with properties similar to those of mammalian MPRs, and that targeting of
      lysosomal enzymes by MPRs represents an ancient pathway in vertebrate cell
      biology. We also determined the expression patterns of the CD-MPR and CI-MPR
      during embryonic development in zebrafish. Both genes are expressed from the one
      cell stage through to the hatching period. In early embryos, expression is
      ubiquitous, but in later stages, expression of both receptors is restricted to
      the anterior region of the embryo, covering the forebrain, midbrain and
      hindbrain. The expression patterns suggest time- and tissue-specific functions
      for the receptors, with particular evidence for roles in neural development. Our
      study establishes zebrafish as a novel, genetically tractable model for in vivo
      studies of MPR function and lysosome biogenesis.

PMID- 16411120
TI  - Impregnation of cancellous bone to treat infected nonunions: promising technique
      with insufficient data.

PMID- 16411118
TI  - Cloning of matrix Gla protein in a marine cartilaginous fish, Prionace glauca:
      preferential protein accumulation in skeletal and vascular systems.
AB  - Matrix Gla protein (MGP) belongs to the family of vitamin K dependent, Gla
      containing proteins and, in mammals, birds and Xenopus, its mRNA has been
      previously detected in bone, cartilage and soft tissue extracts, while the
      accumulation of the protein was found mainly in calcified tissues. More recently,
      the MGP gene expression was also studied in marine teleost fish where it was
      found to be associated with chondrocytes, smooth muscle and endothelial cells. To
      date no information is available on the sites of MGP expression or accumulation
      in cartilaginous fishes that diverged from osteichthyans, a group that includes
      mammals, over 400 million years ago. The main objectives of this work were to
      study the sites of MGP gene expression and protein accumulation by means of in
      situ hybridization and immunohistochemistry. MGP mRNA and protein were localized
      as expected not only in cartilage from branchial arches and vertebra but also in
      the endothelia of the vascular system as well as in the tubular renal
      endothelium. The accumulation of MGP in non mineralized soft tissues was
      unexpected and suggests differences in localization or regulation of this protein
      in shark soft tissues compared to tetrapods and teleosts. Our results also
      corroborate the hypothesis that in Prionace glauca, as previously shown in
      mammals, the MGP protein probably also acts as a calcification inhibitor,
      protecting soft tissues from abnormal and ectopic calcification.

PMID- 16411122
TI  - Treatment of distal radius fractures: the title or the conclusion?

PMID- 16411123
TI  - Healing potential of transplanted allogeneic chondrocytes of three different
      sources in lesions of the avascular zone of the meniscus: a pilot study.
AB  - Successful treatment of tears to the avascular region of the meniscus remains a
      challenge. Current repair techniques, such as sutures and anchors, are effective
      in stabilizing the peripheral, vascularized regions of the meniscus, but are not
      adequate for promoting healing in the avascular region. The purpose of this study
      was to demonstrate the healing ability of a tissue-engineered repair technique
      using allogenic chondrocytes from three different sources for the avascular zone
      of the meniscus. MATERIAL AND METHODS: Articular, auricular, and costal
      chondrocytes were harvested from 3-month-old Yorkshire swine. A 1-cm bucket
      handle lesion was created in the avascular zone of each three swine. A cell
      scaffold construct, composed of a single chondrocyte cell type and Vicryl mesh,
      was implanted into the lesion and secured with two vertical mattress sutures.
      Controls consisted of each three sutured unseeded mesh implants, suture only, and
      untreated lesions. The swine were allowed immediate post-operative full weight
      bearing. Menisci and controls were harvested after 12 weeks. RESULTS: In all
      experimental samples, lesion closure was observed. Gross mechanical testing with
      two Adson forceps demonstrated bonding of the lesion. Histological analysis
      showed formation of new tissue in all three experimental samples. None of the
      control samples demonstrated closure and formation of new matrix. CONCLUSION: We
      present preliminary data that demonstrates the potential of a tissue-engineered,
      allogenic cellular repair to provide successful healing of lesions in the
      avascular zone in a large animal model.

PMID- 16411124
TI  - Bacteremic pneumococcal pneumonia associated with macrolide failure.
AB  - Despite rising rates of macrolide resistance to Streptococcus pneumoniae, the
      current guidelines for outpatient treatment of community-acquired pneumonia
      include a macrolide as initial empiric therapy. There have only been a few
      previously documented cases of macrolide treatment failure in community-acquired
      pneumonia and there is controversy as to whether macrolide resistance in S.
      pneumoniae is clinically important. Reported here are two cases of community
      acquired pneumonia caused by S. pneumoniae, one of which was fatal, that failed
      to respond to clarithromycin.

PMID- 16411126
TI  - Clusterin induces differentiation of pancreatic duct cells into insulin-secreting
      cells.
AB  - AIMS/HYPOTHESIS: We recently reported that expression of the gene encoding
      clusterin (Clu) is upregulated in the regenerating pancreas, particularly in
      tissues undergoing differentiation. This led us to propose that clusterin
      participates in the cytodifferentiation of pancreatic tissue, particularly the
      endocrine islet cells. The aim of this study was to investigate whether clusterin
      induces the differentiation of duct-lining cells into insulin-secreting cells.
      METHODS: We isolated ductal tissue from rat pancreas and cultured it to develop
      epithelial cell explants for transfection of the Clu cDNA as well as for
      treatment of clusterin protein. RESULTS: The number of newly differentiated
      insulin cells increased 6.9-fold upon Clu overexpression compared with controls.
      Ins1 mRNA and peptide levels were also increased. Furthermore, glucose-stimulated
      insulin secretion was observed in the differentiated insulin cells. These cells
      were immunoreactive for insulin and C-peptide, but negative for other islet
      hormones and for cytokeratin-20, which indicates a fully differentiated state.
      Insulin cell differentiation was also increased in a dose-dependent manner by
      treating duct cells in culture with clusterin, indicating a growth-factor-like
      action of clusterin in insulin cell differentiation. CONCLUSIONS/INTERPRETATION:
      These results suggest that clusterin can be considered as a potential morphogenic
      factor that promotes differentiation of pancreatic beta cells.

PMID- 16411125
TI  - [Functional disorders and functional diseases in the region of the upper cervical
      spine particularly regarding the cervical joints. Current status and clinical
      relevance].
AB  - Functional disorders of the upper cervical spine may be responsible for or the
      primary cause of persistent complaints following an injury or illness. Functional
      disorders involving the cervical joints, especially C0/C1 and C1/2 but also the
      C2/3 junction are of particular clinical relevance. Range of motion assessment is
      extremely important for the diagnosis of joint disorders. Hypomobility or
      "blockade" can be diagnosed using special examination techniques that, in many
      cases, can be extended for direct manual therapy. Periarticular structures
      involved in these dysfunctional processes, especially muscles and fasciae, must
      also be examined and treated. Clinical manifestations may include locally
      restricted muscle extensibility (e.g., trigger points, tension or muscle
      shortening) with zones of radiating pain as well as referred problems distal to
      the primary lesion. Functional disorders in the region of the upper cervical
      spine may be accompanied by various types of reflexive compensatory problems.
      Although they must be diagnosed separately, these disorders frequently respond to
      the manual therapy techniques used to treat the underlying functional problem.
      Even if the exact correlations to functional medicine cannot be scientifically
      demonstrated in every case, functional assessment and treatment techniques are,
      in our view, a useful addition to the armamentarium for orthopedic diagnosis and
      treatment.

PMID- 16411127
TI  - Acid-base metabolism: implications for kidney stones formation.
AB  - The physiology and pathophysiology of renal H+ ion excretion and urinary buffer
      systems are reviewed. The main focus is on the two major conditions related to
      acid-base metabolism that cause kidney stone formation, i.e., distal renal
      tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid
      stone formation. Both the entities can be seen on the background of disturbances
      of the major urinary buffer system, NH3+ <--> NH4+. On the one hand, reduced
      distal tubular secretion of H+ ions results in an abnormally high urinary pH and
      either incomplete or complete dRTA. On the other hand, reduced
      production/availability of NH4+ is the cause of an abnormally low urinary pH,
      which predisposes to uric acid stone formation. Most recent research indicates
      that the latter abnormality may be a renal manifestation of the increasingly
      prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH
      values, both the dRTA and uric acid stone formation due to low urinary pH require
      the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the
      body's buffer capacity, whereas the goal of alkali treatment in uric acid stone
      formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid
      crystallization.

PMID- 16411129
TI  - The Michel Benoist and Robert Mulholland yearly European Spine Journal review: a
      survey of the "surgical and research" articles in the European Spine Journal,
      2005.

PMID- 16411131
TI  - Direct comparison between genomic constitution and flavonoid contents in Allium
      multiple alien addition lines reveals chromosomal locations of genes related to
      biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of
      shallot (Allium cepa L.).
AB  - The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important
      role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot
      monosomic addition lines (FF+nA). This study deals with the production and
      biochemical characterisation of A. fistulosum-shallot multiple alien addition
      lines carrying at least 5A to determine the chromosomal locations of genes for
      quercetin formation. The multiple alien additions were selected from the crossing
      between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113
      plants obtained from this cross were analysed by a chromosome 5A-specific PGI
      isozyme marker of shallot. Thirty plants were preliminarily selected for an alien
      addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to
      23. The other extrachromosomes in 19 plants were completely identified by using
      seven other chromosome markers of shallot. High-performance liquid chromatography
      analyses of the 19 multiple additions were conducted to identify the flavonoid
      compounds produced in the scaly leaves. Direct comparisons between the
      chromosomal constitution and the flavonoid contents of the multiple alien
      additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis
      of quercetin from kaempferol was located on 7A and that an anonymous gene
      involved in the glucosidation of quercetin was on 3A or 4A. As a result of
      supplemental SCAR analyses by using genomic DNAs from two complete sets of A.
      fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol
      synthase to 4A.

PMID- 16411130
TI  - The Michel Benoist and Robert Mulholland yearly European Spine Journal Review: a
      survey of the "medical" articles in the European Spine Journal, 2005.

PMID- 16411132
TI  - CD56 expression aids in the differential diagnosis of cholangiocarcinomas and
      benign cholangiocellular lesions.
AB  - CD56 (neuronal cell adhesion molecule, N-CAM) has been reported in neuroendocrine
      tumours and as a marker of reactive biliary epithelial cells. However, up to
      date, it is not used to distinguish malignant from non-malignant biliary lesions.
      In this study, we systematically examined CD56 expression on 98 tumours arising
      from the biliary tree as well as intrahepatic conditions with reactive
      neoductules. When neuroendocrine carcinomas are excluded, only 4 of 32 (12.5%)
      cholangiocarcinomas expressed CD56, 2 of which showed clear cell morphology.
      Reactive bile ductules adjacent to cirrhotic nodules as well as in focal nodular
      hyperplasia were CD56 positive. Twelve of 17 (70.5%) bile duct adenomas were CD56
      positive, whereas von Meyenburg complexes expressed CD56 only very focally in
      less than 5% of lesional cells. Bile duct cysts were negative for CD56 with the
      exception of focally interspersed neuroendocrine cells, similar to that seen in
      segmental bile ducts. Thus, if van Meyenburg complexes are excluded, CD56 can be
      used to differentiate intrahepatic non-neoplastic from neoplastic proliferations,
      which is a helpful diagnostic tool in small liver biopsies.

PMID- 16411133
TI  - Salivary hybrid tumour: adenoid cystic carcinoma and basal cell adenocarcinoma.

PMID- 16411134
TI  - Podoplanin is expressed in subsets of tumors of the central nervous system.
AB  - Immunohistochemical analyses with the monoclonal antibody D2-40 were performed to
      ascertain the expression of podoplanin (a.k.a. T1-alpha, gp36, or aggrus) in
      tumors of the central nervous system (CNS) and to determine the diagnostic
      utility of the antibody. The analyses were performed on 325 tumors of various
      histologic types. The chief finding was almost constant immunoreactivity in
      ependymal tumors (37/40, 92.5%), choroid plexus papillomas (8/8, 100%), and
      meningiomas (100/100, 100%). The reactivity was considered "tissue-specific," as
      the corresponding normal tissue of each tumor was also found to express
      podoplanin. In addition, expression, not committed to the lineages, was found in
      many other tumor types, including astrocytic tumors, medulloblastomas, and
      hemangioblastomas, with variable frequency and intensity. The way of expression
      was not fully understood, but the expression in astrocytic tumors seemed to be
      associated with pronounced fibrous properties or malignant phenotype, as was
      shown by high-frequent expression in pilocytic astrocytomas (12/12, 100%) and
      glioblastomas (29/35, 82.9%). The present study has shown that podoplanin is
      expressed in several types of CNS tumors with variable frequency and intensity.
      Given the widespread expression of podoplanin, the antibody D2-40 is of little
      use in diagnostic practice for CNS tumors.

PMID- 16411135
TI  - Will the next human influenza pandemic be caused by the virus of the avian flu
      A/H5N1? Arguments pro and counter.
AB  - In 1997, the avian influenza A subtype H5N1 that caused big outbreaks of fowl
      pest in mass poultry farming had emerged in Hong Kong. Its spread throughout
      Eurasia had given rise to concerns in terms of the possible imminence of the next
      human influenza pandemic. In this article, epidemiological and virological
      arguments supporting or declining this fear are outlined and discussed with
      regard to viral infectivity and pathogenicity.

PMID- 16411136
TI  - Toxicological comments to the discussion about REACH.
AB  - It is the ultimate goal of the intended REACH process (Registration, Evaluation
      and Authorization of Chemicals) of the European Union to identify substances of
      hazardous properties and to evaluate the risks of human and environmental
      exposure. During the last few months there has been a controversial discussion as
      to what extent in vitro studies and consideration of structure activity
      relationship provide sufficient information to waive repeated exposure studies.
      Industry as well as certain regulatory agencies or NGOs support this approach and
      propose that repeated dose studies may only be required beyond 100 t/a. From a
      toxicological point of view it has to be stressed that this discussion primarily
      considers the cost reduction and protection of animals, whereas protection of
      human health and the environment are secondary. In vitro studies only allow
      identification of specific hazardous properties which can be detected by the
      specific test system. Moreover, appropriate information on the dose response of
      adverse effects, identification of thresholds and NOELs that are essential for
      risk characterization cannot be obtained from these studies. Consequently,
      identification of all relevant hazardous properties and endpoints of adverse
      effects can only be determined in the intact animal by repeated dose studies such
      as 28-day or 90-day studies. In the absence of such information the hazard
      identification is incomplete and there is no basis for appropriate risk
      assessment of human exposure. Thus, any waiving of repeated dose studies in
      animals bears the probability of unforeseen effects in case of acute or
      continuous human exposure. From this the undersigning European Toxicologists
      conclude: 1. The intention of REACH is to identify hazardous properties in order
      that a reliable risk assessment can be made and measures taken to deal with
      chemicals posing a significant risk. 2. The recent debate has centered on ways in
      which the well established in vivo methods for risk assessment can be bypassed.
      3. The evidence that the available alternatives would support such replacement is
      weak. Progress to improve their value for risk assessment purposes is bound to be
      slow because the issues are very complex. As a group of European Toxicologists we
      strongly support the need for more research support in these areas, but we
      believe that over claims for progress is damaging their development. 4. Under the
      circumstances only two options are available: to reduce very substantially the
      estimation of hazard and risk with inevitable adverse consequences for human
      health and environmental protection, or to continue the existing methods until
      properly validated new methods are available.

PMID- 16411138
TI  - Reconstruction of the anterior cruciate ligament using bone-patellar tendon-bone
      graft with double biodegradable femoral pin fixation.
AB  - The purpose of this study was to evaluate the early clinical outcomes of the bone
      patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction using
      biodegradable cross pin fixation. The nature of this study is a prospective
      nonrandomized clinical outcome study. Thirty-five patients who underwent BPTB ACL
      reconstruction with a minimum of 2 years follow-up evaluation were included in
      the study. Thirty BPTB autografts and five BPTB allografts were fixed with two
      biodegradable 2.7 mm cross pins (Rigid Fix) on the femoral side. Clinical
      evaluation included International Knee Documentation Committee (IKDC), Lysholm
      and Tegner activity score, and Telos stress device measurements. The average
      Lysholm knee score was 94.7 (of 100). Twenty-four patients reported an excellent
      result. The other eight patients were in a good group. According to the IKDC
      scores, 23 (66%) patients reported normal function, 12 (34%) patients reported
      nearly normal function, and no (0%) patient reported abnormal or severely
      abnormal function. Telos stress device values were less than 3 mm of sagittal
      displacement in 28 patients and 5 mm in 7 patients. No patients complained that
      their knees gave way fully, even with moderate or strenuous activities. All of
      the patients have returned to their preinjury level of activity and athletic
      participation. Clinical results support this technique as a reliable alternative
      for patellar tendon fixation in ACL reconstruction.

PMID- 16411137
TI  - Electrophysiological characterization of three non-synonymous single nucleotide
      polymorphisms (R87Q, A251T, and P307S) found in hKv1.5.
AB  - Non-synonymous single nucleotide polymorphisms (SNPs) in the KCNA5/hKv1.5 gene,
      which encodes for a voltage-gated K+ channel responsible for the I (Kur) current
      in the human atria, have been recently reported. To gain further knowledge on
      potential influence of hKv1.5 SNPs, we searched for their presence in a specific
      population of 96 French-Canadians and characterized electrophysiological
      properties of the variants in two cell lines. The presumed promoter (-83 bp) and
      coding regions were sequenced. We found three heterozygous SNPs: R87Q, A251T, and
      P307S. Functional analysis of SNPs transfected in Chinese hamster ovary (CHO)
      cells showed that both R87Q and P307S diminished the inactivation amplitude
      (e.g., at +60 mV, amplitudes were 89+/-26, 23+/-4, and 22+/-7 pA/pF for the wild
      type, R87Q and P307S, respectively; n=8, 6, and 8, respectively). Inactivation
      was slowed with these variants (e.g., tau (fast) at +50 mV were 270+/-48, 490+/
      66, and 340+/-45 ms for the wild type, R87Q, and P307S, respectively) while R87Q
      additionally accelerated the rate of hKv1.5 channel opening. A dominant-negative
      effect was observed for R87Q but not for P307S. SNPs properties were not
      reproduced when expressed in the HEK293 cell line, suggesting that the regulatory
      beta-subunit present in CHO cells (and the human heart) is essential for the SNPs
      effects that we have observed.

PMID- 16411140
TI  - Colonic interposition and supercharge for esophageal reconstruction.
AB  - AIMS: We evaluated the techniques of colonic interposition and supercharge for
      esophageal reconstruction and discussed the main considerations related to these
      procedures. PATIENTS AND METHODS: In this study, we performed 51 esophageal
      reconstructions using colonic interposition. Twenty-eight of the 51 patients had
      synchronous or allochronic gastric malignancy. We selected colonic interposition
      for high anastomosis in 11 patients and also for esophageal bypass in 3 patients.
      This procedure was also selected to preserve gastric function in 5 patients. We
      recently performed the supercharge technique for colonic interposition in 41
      patients. RESULTS: Despite the long duration and multistep nature of the
      operation procedure, no perioperative complications were noted. The patients
      returned to a good quality of life. The incidence of postoperative weight loss
      did not differ significantly between the colonic reconstruction group and the
      gastric reconstruction group. In terms of heartburn and dumping syndrome, the
      outcome was markedly better in the colonic reconstruction group (no cases of
      heartburn or dumping syndrome) than that in the gastric reconstruction group.
      CONCLUSION: For reconstruction of the esophagus, the colonic interposition and
      supercharge technique is advantageous and contributes to the patient's quality of
      life.

PMID- 16411141
TI  - Hepatoma-derived growth factor is a novel prognostic factor for hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatoma-derived growth factor (HDGF) is involved in
      hepatocarcinogenesis, as well as in liver development and regeneration. This
      study investigated the correlation of HDGF expression with differentiation and
      prognosis of hepatocellular carcinoma (HCC). METHODS: HDGF expression in 100
      patients with HCC (81 men and 19 women) with ages ranging from 34 to 81 years
      (median, 61 years) receiving surgical treatment was analyzed by
      immunohistochemistry. HDGF messenger RNA expression was evaluated in 10 cases by
      reverse transcription-polymerase chain reaction. The immunostaining pattern in
      HCCs was categorized as a positive HDGF index (showing positive staining in >90%
      of tumor cells in both nucleus and cytoplasm) or a negative HDGF index (all
      others). RESULTS: Twenty-seven cases (27%) showed a positive and 73 (73%) showed
      a negative HDGF index. HDGF messenger RNA expression was significantly higher in
      four cases with a positive HDGF index than in six with a negative index. Cases
      with well-differentiated histological characteristics showed a higher rate of
      positive HDGF index than those with a poorly differentiated subtype. Univariate
      and multivariate analysis revealed significantly poorer disease-free and overall
      survivals in patients with a positive HDGF index compared with patients with a
      negative index. CONCLUSIONS: These findings suggest the potential utility of HDGF
      immunohistochemistry in determining the prognosis of HCC.

PMID- 16411142
TI  - Putting the chemo in chemoradiation for pancreatic cancer.

PMID- 16411144
TI  - Surgery combined with intraoperative brachytherapy in the treatment of
      retroperitoneal sarcomas.
AB  - BACKGROUND: The purpose of this study was to analyze the results of treatment of
      retroperitoneal soft tissue sarcomas (RSTS) by surgery combined with
      intraoperative brachytherapy (IOBRT). METHODS: Seventy adult patients with RSTS
      were considered for combined treatment (surgery plus IOBRT) between June 1998 and
      February 2004. There were 64 (91%) recurrent tumors, and 93% of tumors exceeded 5
      cm. IOBRT was performed with high-dose-rate Gammamed 12 with iridium 192 (IOBRT
      time range, 20-87 minutes; median, 56 minutes). RESULTS: After intraoperative re
      evaluation, 24 patients (34%) were found to be ineligible for IOBRT because of
      multiple intraperitoneal recurrences, macroscopically nonradical resection, poor
      general condition, and technical aspects. Thirty-seven patients underwent IOBRT
      immediately after surgery during the same general anesthesia procedure. Nine
      patients underwent delayed IOBRT within 1 to 3 days after the primary operation.
      Ten (21.5%) of 46 patients underwent reoperation because of surgical
      complications. One patient died in the postoperative period. After IOBRT, 24
      patients (52%) underwent adjuvant external beam radiotherapy (EBRT) to a total
      dose of 50 Gy. Over a median follow-up time of 20 months, the estimated 5-year
      overall survival and local recurrence-free survival rates in IOBRT patients were
      55% and 51%, respectively. Application of adjuvant EBRT showed a favorable local
      control rate. CONCLUSIONS: The scheduled combined treatment (surgery plus IOBRT)
      was possible to perform in 66% of RSTS cases that received surgical treatment.
      The complication rate was high, but we consider it acceptable because of the
      necessity for extensive aggressive surgical treatment in regionally advanced
      RSTS. EBRT seems to be an indispensable part of treatment that provides better
      local control.

PMID- 16411143
TI  - Outcomes of mass screening for gastric carcinoma.
AB  - BACKGROUND: Therapeutic results of gastric cancer have been improved by early
      detection of gastric cancer with the mass screening system in Japan. The
      objective of our study was to assess the efficacy of mass screening for gastric
      cancer by using a barium meal. METHODS: A series of 1050 patients (364 in the
      screened group and 686 in the nonscreened group) were included in this study from
      April 1992 to March 2000. Patient characteristics, therapeutic results, and
      prognostic factors were compared in the two groups. RESULTS: The screened
      patients tended to be younger and male, with tumors in the middle third of the
      stomach that were of a macroscopically superficial type, with a smaller diameter,
      and at an earlier stage. They had fewer metastatic lymph nodes and underwent more
      frequent curative resection. Among the screened patients with curatively resected
      disease, tumors tended to be of a smaller diameter, and there were fewer
      metastatic lymph nodes in both early and advanced cases. Disease-specific
      survival was significantly better in the screened cases among all registered and
      curatively resected patients. Mass screening achieved significantly better
      surgical results in early or advanced gastric cancer patients who received
      curative resection. Multivariate analysis revealed that mass screening was an
      independent prognostic factor (hazard ratio, .3949; P < .0001), together with
      depth of invasion, lymph node metastasis, age, and tumor diameter. CONCLUSIONS:
      Mass screening by using barium meal examination for gastric cancer detects cancer
      at an early stage and produces good therapeutic results.

PMID- 16411145
TI  - Minimally invasive video-assisted thyroidectomy for follicular neoplasm: is there
      an advantage over conventional thyroidectomy?
AB  - BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) is safe and
      effective for selected patients, but its advantages are not clearly defined.
      Results of MIVAT for follicular neoplasms at a single institution were
      retrospectively evaluated to define its advantages or disadvantages. METHODS:
      Between October 2002 and May 2004, 22 patients underwent MIVAT. Twenty-six
      patients who underwent conventional thyroidectomy during the same time period
      served as matched controls. Operative times, pathologic findings, complications,
      analgesic requirements, and incision lengths were retrospectively evaluated.
      RESULTS: Four MIVAT and three conventional surgery patients underwent total
      thyroidectomy. Eighteen MIVAT and 23 conventional patients underwent
      hemithyroidectomy. The operative time (mean +/- SEM) for hemithyroidectomy was
      102 +/- 4 minutes for MIVAT and 86 +/- 3 minutes for conventional surgery (P <
      .05). In subgroup analysis that excluded patients with thyroiditis, operative
      times were not significantly different: MIVAT, 99 +/- 4 minutes; conventional, 88
      +/- 4 minutes. The mean incision length was 2.3 +/- .5 cm in the MIVAT group.
      Conventional thyroidectomy was performed through a 4- to 5-cm incision. The
      average amount of narcotic used was not significantly different (intravenous, 9.9
      +/- 3.1 mg [MIVAT] vs. 12.4 +/- 3.8 mg; oral, 10.3 +/- 4.2 mg [MIVAT] vs. 3.5 +/-
      2.0 mg). The conventional group received more cyclooxygenase 2 inhibitor (527 +/-
      9 mg vs. 187 +/- 84 mg; P < .05). One patient in each group experienced transient
      hoarseness. There were no cases of permanent hypoparathyroidism or recurrent
      laryngeal nerve injury in either group. CONCLUSIONS: MIVAT is as safe and
      effective as conventional thyroidectomy and is associated with similar narcotic
      analgesic requirements, but it can be performed through smaller incisions.
      Operative times were significantly longer for MIVAT, but when patients with
      thyroiditis were excluded, operative times were not significantly different.

PMID- 16411146
TI  - Diffuse sclerosing variant of papillary carcinoma of the thyroid: a 35-year
      comparative study at a single institution.
AB  - BACKGROUND: Diffuse sclerosing variant (DSV) is a rare variant of papillary
      thyroid carcinoma (PTC), and the features of this carcinoma have not been fully
      characterized. The aim of this study was to analyze the clinicopathologic
      features of a large cohort of patients with this disease. METHODS: We
      reclassified primary thyroid carcinomas treated in a 35-year study period and
      studied the clinicopathologic features and outcomes of DSV of PTC in comparison
      with classic PTC. RESULTS: Fifteen patients (2 men and 13 women) with DSV of PTC
      were identified who had surgical resection of the thyroid. Fine-needle aspiration
      biopsy diagnosed 83% (10 of 12) of the tumors. Compared with classic PTC,
      patients with DSV presented at a younger age (mean age, 29 vs. 46 years; P =
      .0001), had larger tumors (mean diameter, 3.6 vs. 2.2 cm; P = .002), and had a
      higher incidence of cervical nodal metastases (80% vs. 43%; P = .006). Ten
      patients had received postoperative iodine 131 ablation, and four had also
      received external-beam irradiation. Distant metastases were detected in two
      patients (one in lung and one in brain). One third (5 of 15) of the patients
      developed disease recurrence. Lymph node recurrence was detected in one patient
      12 years after the initial operation. Over a median follow-up period of 10.7
      years, one patient with an initial incomplete excision died of the carcinoma. The
      overall disease-specific survival rate was 93%. CONCLUSIONS: DSV of PTC had
      distinctive clinicopathologic features and a high incidence of recurrence after
      operation but had a prognosis similar to that of classic PTC.

PMID- 16411147
TI  - Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal
      peptide drug delivery system.
AB  - PURPOSE: Intravenous application of pituitary adenylate cyclase-activating
      polypeptide (PACAP) has been identified as a promising strategy for the treatment
      of type 2 diabetes. To generate a more applicable formulation, it was the aim of
      this study to develop a sustained buccal delivery system for this promising
      therapeutic peptide. METHODS: 2-Iminothiolane was covalently bound to chitosan to
      improve the mucoadhesive and permeation-enhancing properties of chitosan used as
      drug carrier matrix. The resulting chitosan-4-thiobutylamidine conjugate was
      homogenized with the enzyme inhibitor and permeation mediator glutathione (gamma
      Glu-Cys-Gly), Brij 35, and PACAP (formulation A). The mixture was lyophilized and
      compressed into flat-faced discs (18 mm in diameter). One formulation was
      additionally coated on one side with palm wax (formulation B). Tablets consisting
      of unmodified chitosan and PACAP (formulation C) or of unmodified chitosan, Brij
      35, and PACAP (formulation D) served as controls. Bioavailability studies were
      performed in pigs by buccal administration of these test formulations. Blood
      samples were analyzed via an ELISA method. RESULTS: Formulations A and B led to
      an absolute bioavailability of 1%, whereas PACAP did not reach the systemic
      circulation when administered via formulations C and D. Moreover, in the case of
      formulations A and B, a continuously raised plasma level of the peptide drug
      being in the therapeutic range could be maintained over the whole period of
      application (6 h). Formulations A and B were removed by moderate force from the
      buccal mucosa after 6 h, whereas formulations C and D detached from the mucosa 4
      h after application. CONCLUSION: The study reveals this novel mucoadhesive
      delivery system to be a promising approach for buccal delivery of PACAP.

PMID- 16411148
TI  - Pharmacologic and pharmacokinetic assessment of anti-TGFbeta2 aptamers in rabbit
      plasma and aqueous humor.
AB  - PURPOSE: The aim of the study is to determine the bioactivity and effects of
      PEGylation on the pharmacokinetics in rabbit aqueous humor and plasma of an
      aptamer directed against TGFbeta2. METHODS: Pharmacological activity of anti
      TGFbeta2 aptamer in rabbit ocular fluid was demonstrated using a mink lung
      epithelial cell proliferation assay. For pharmacokinetic analyses, concentrations
      of aptamers in plasma and aqueous humor were determined over time following
      bilateral subconjunctival administration to Dutch-belted rabbits using a
      hybridization-based pseudo-enzyme-linked immunosorbent assay (ELISA) assay.
      RESULTS: Anti-TGFbeta2 aptamer (ARC81) binds to human TGFbeta2 with a K(D) of
      approximately 5 nM and inhibits the activity of human TGFbeta2 in vitro in a cell
      based assay with an IC(50) of approximately 100 nM. ARC81 blocks endogenously
      derived TGFbeta2 in rabbit aqueous humor in vitro with an IC(50) of approximately
      200 nM and an IC(90) of approximately 1 microM. In vivo in rabbit, ARC81 [no
      polyethylene glycol (PEG)] entered systemic circulation rapidly (t(max) = 1 h in
      plasma) relative to aptamer conjugates ARC117 (20 kDa PEG) and ARC119 (40 kDa
      PEG), which showed prolonged residence in the subconjunctival space and aqueous
      compartment (t(max) = 6 and 12 h, respectively, in plasma). Both 20- and 40-kDa
      aptamer conjugates reached maximal concentrations (C(max)) in aqueous humor of 23
      30 nM and remained at or above 1 nM for as long as 12 h. CONCLUSIONS:
      Pharmacologically active levels of anti-TGFbeta2 aptamers can be sustained in the
      ocular fluid and local tissue environment over a 12-h period after single
      administration. Daily subconjunctival administration of PEGylated anti-TGFbeta2
      aptamers should allow further pharmacological evaluation of these agents in a
      rabbit conjunctival scarring model. Perioperative administration, via
      subconjunctival injection, may prove to be an effective means to deliver
      therapeutic quantities of TGFbeta2 aptamer conjugates in trabeculectomy
      procedures.

PMID- 16411150
TI  - Giant atria in children with endomyocardial fibrosis.

PMID- 16411149
TI  - Specific delivery of corroles to cells via noncovalent conjugates with viral
      proteins.
AB  - PURPOSE: Corroles are amphiphilic macrocycles that can bind and transport metal
      ions, and thus may be toxic to cells. We predicted that anionic corroles would
      poorly enter cells due to the negatively charged cell membrane, but could be
      ideal tumor-targeted drugs if appropriate carriers enabled delivery into tumor
      cells. In this work, we test the hypothesis that recombinant cell penetrating
      proteins of the adenovirus (Ad) capsid form noncovalent conjugates with corroles
      to facilitate target-specific delivery and cell death. METHODS: Corroles mixed
      with recombinant proteins were tested for conjugate assembly, cell penetration,
      stability, targeted binding, and cell killing in vitro. RESULTS: Sulfonated
      corroles entered cells only with carrier proteins, and formed stable complexes
      with recombinant Ad capsid proteins. ErbB receptor-targeted conjugates were
      cytotoxic to ErbB2-positive but not ErbB2-negative breast cancer cells, whereas
      molar equivalents of free corrole had no effect on these cells. CONCLUSIONS:
      Sulfonated corroles are cytotoxic to ErbB2-positive breast cancer cells when
      delivered by a targeted cell penetrating protein. The relatively low dose
      required to accomplish this compared to untargeted compounds suggests that
      corroles may lend themselves to targeted therapy. Importantly, the amphiphilicity
      of corroles enables a unique approach to bioconjugate formation whereby the
      carrier and drug form a stable complex by noncovalent assembly.

PMID- 16411152
TI  - Absent left superior vena cava with persistent right superior vena cava in
      visceroatrial situs inversus.
AB  - We report an unusual anomaly of the upper body venous drainage in a patient with
      visceroatrial situs inversus. The patient had a persistent right superior vena
      cava draining into the left-sided right atrium by way of the coronary sinus, with
      the absence of the left superior vena cava associated with atrioventricular
      discordant levocardia, pulmonary atresia, and ventricular septal defect.

PMID- 16411151
TI  - Management strategy for very mild aortic valve stenosis.
AB  - It is unclear how often patients with very mild aortic stenosis (gradients < 25
      mmHg) need interval follow-up. The purpose of this study was to define the
      determinants of disease severity progression and to propose appropriate
      management strategies. It is known that congenital aortic stenosis is a
      progressive disease that requires long-term follow-up at consistent intervals. We
      studied 89 patients with very mild aortic stenosis. Cox proportional hazard
      modeling was performed to ascertain predictors of morbidity and mortality. Events
      were defined as valve surgery or death. Of the original 89 patients, 7 died (92%
      survival); one death was sudden and unexplained and six were noncardiac. Eighteen
      individuals were lost to follow-up (10 not located and 8 refused participation).
      Twelve (17%) had valve surgery. The minimum time interval between initial
      diagnosis of very mild aortic stenosis and surgery was 4.6 years (mean, 14.0).
      Age at diagnosis, gender, initial gradient, initial gradient/age, and aortic
      regurgitation were found not to be predictive of outcome. However, the slope of
      the transaortic gradient [change of gradient/time (years)] was predictive of
      outcome (hazard ratio of 1.69; confidence interval, 1.4-2.2). At least 17% of
      these patients progress to require operation. For patients with a gradient slope
      < 1.1, evaluation every 4 or 5 years is recommended. For patients with a gradient
      slope > 1.2, evaluation every 1 or 2 years seems prudent.

PMID- 16411153
TI  - Compensatory hypertrophy of calf muscles after selective neurectomy.
AB  - BACKGROUND: Unexpected contour changes frequently occurred after surgical
      contouring of the calves by selective neurectomy of the nerve to the medial
      gastrocnemius muscle. We recently experienced a rather unusual case, in which the
      nerve to the medial gastrocnemius muscle was selectively transected on one side,
      whereas on the other side, the nerve to the soleus was transected by mistake.
      METHODS: To investigate the reason for the contour change, the authors compared
      the muscle volume ratio of the posterior compartment of eight normal calves of
      eight normal volunteers with two calves in the reported case by using MRIs.
      RESULTS: The volume ration of normal control calves was 0.22:0.12:0.66,
      respectively, for the medial and lateral gastrocnemius muscles and the soleus
      muscle. In the case of the calf with atrophy of the medial gastrocnemius muscle,
      the volume ratio was 0.13:0.20:0.67, respectively. In the case of the calf with
      atrophy of the soleus muscle, the volume ratio was 0.27:0.14:0.59, respectively.
      CONCLUSIONS: Physician and the patient should keep in mind before the operation
      that even though one muscle in the calf is selectively atrophied after the
      selective neurectomy, the other muscles can hypertrophy for compensation, thus
      causing possible distortion of aesthetic result.

PMID- 16411154
TI  - Psychosocial aspects of botox in aesthetic surgery.
AB  - BACKGROUND: The human preoccupation of experimenting with potentially toxic
      substances at sublethal doses to enhance beauty spans the ages. The Botox
      injection is the fastest growing cosmetic procedure, and its physiologic safety
      profile is considered to be excellent. The psychosocial consequences of Botox
      have been largely ignored in the literature. METHODS: This cross-sectional study
      investigated the psychosocial issues that can arise as either an antecedent to
      the treatment or a consequence of it. RESULTS: Significant differences between
      clients and control subjects were observed in the four major areas of
      psychosocial functioning implicated in this study: (a) distress arising from the
      procedure (anxiety/phobia), (b) worry about the facial changes after the
      procedure, (c) expectations, involving the discrepancy between expected and
      actual outcomes of treatment; and (d) dependence, involving the desire for
      repetitive administration. CONCLUSIONS: The impact of Botox on the psychosocial
      functioning of individuals was investigated in this study from a psychosocial and
      clinical perspective in an effort to pave the way for the formulation of national
      standardized guidelines for the use of Botox. This study empowers the clinician
      to understand the basis for the relative contraindications of Botox, which are
      largely psychological in nature, and thus to ensure its administration in a safe
      and responsible manner.

PMID- 16411155
TI  - Guidelines for pubic hair restoration.
AB  - BACKGROUND: Although the loss of pubic hair is a relatively frequent condition,
      there have been few reports about pubic hair restoration. This report aims to
      describe the demarcation and technical guidelines for pubic hair restoration
      using follicular micrografts. METHODS: Demarcation is described and based on
      anatomic parameters such as the level of the greater trochanters and the labium
      majus. The angle of micrograft insertion and direction also are described.
      RESULTS: The use of micrografts for pubic hair restoration is a procedure that
      promotes very natural results. CONCLUSIONS: The described parameters of
      demarcation and technical details are important issues that should be considered
      to obtain a natural result in pubic hair restoration.

PMID- 16411156
TI  - The use of high-density porous polyethylene as a custom-made nasal spreader
      graft.
AB  - The concept and technique of using high-density porous polyethylene (HDPP), a
      nonresorbable synthetic material, for nasal spreader grafts, are presented. This
      material is thought to be particularly useful in revision (secondary or tertiary)
      rhinoplasty, in which internal valve collapse frequently is confronted and septal
      cartilage often is unavailable because it has been harvested for spreader or
      other grafts. Sold as a thin plain sheet (0.85 x 38 x 50 mm) that can be cut to
      an appropriate size for spreader grafts, HDPP is a ready-to-use material
      commercially available on the market. Because HDPP permits ingrowths of fibrous
      tissue inside and around, it is a nonabsorbable material that stabilizes the
      upper lateral cartilages in their new position and maintains the appropriate
      internal valve angle. The authors used this material for 15 patients undergoing
      secondary (n = 12) and tertiary (n = 3) rhinoplasty because of valvular collapse.
      During the mean follow-up period of 16 months (range, 8-30 months), neither
      complication nor recurrence of airway obstruction occurred.

PMID- 16411157
TI  - Contour restoration of the upper limb using solid silicone implants.
AB  - Augmentation of the upper limb, except for the pectoralis major using pectoral
      implants, has been somewhat taboo for plastic surgeons. Deformities of the upper
      limb and muscular deficiencies, however, are aesthetically unattractive or result
      in unacceptable asymmetries. The following implants have been used for
      reconstruction of the upper limb after trauma: deltoid, triceps, and biceps.
      Following the dictum that the implant needs to be placed beneath the muscle
      (i.e., on the humerus for the deltoid and the triceps, and underneath the
      brachialis for the biceps muscles), these implants are deep and act as spacers
      affording the establishment of more volume and symmetry. Access incisions make
      use of incisions previously placed for the repair of previous trauma, fractures
      of the upper limb, or the repair of muscle. Most aesthetic surgeons are not
      familiar with this anatomy, and revision for the morbid anatomy of the upper limb
      is important. Familiarity with the major nerves of the upper limb is paramount,
      particularly familiarity with the radial, ulnar, median, and circumflex humeral
      nerves.

PMID- 16411158
TI  - "Thread seal tape" (polytetrafluoroethylene) implanted in the subcutaneous tissue
      of rats.
AB  - "Thread seal tape" (Polytetrafluoroethylene [PTFE]) was placed in the dorsum of
      20 rats for evaluation of the inflammatory reaction to it. The rats were killed
      7, 14, 28, and 60 days after the surgical intervention, and the implant samples,
      together with adjacent tissues, were removed for histologic analysis. At clinical
      examination, the dorsum of the rat's skin presented no local inflammatory
      reaction. The histologic analysis showed decreasing inflammatory reaction with
      time that was almost absent 60 days after surgery. The authors concluded that the
      "thread seal tape" (PTFE) did not cause an inflammatory reaction when implanted
      in the subcutaneous tissue of rats.

PMID- 16411159
TI  - The cost effectiveness of three different measures of breast volume.
AB  - BACKGROUND: Several methods including water displacement, casting, the Grossman
      Roudner measuring device, photographs, mammograms, ultrasound, and magnetic
      resonance imaging (MRI) have been proposed for the measurement of breast volume.
      The most cost-effective method has not been determined. METHODS: This study
      compared breast volume measurements using the Grossman-Roudner measuring device
      (a piece of circular plastic with a cut along a radius line), plaster casting,
      and MRI. The Grossman-Roudner measuring device was formed into a cone around the
      breast, and the volume was read from a graduated scale on the overlapping edges.
      The volume of the cast was measured using a butter-sand mixture and water
      displacement. The volume from the MRI slices was calculated using the ANALYZE
      bioimaging software. For five women with breast sizes AA, A, B, C, and D, the
      three volume measures were repeated three times. For a single volume measurement,
      the cost of the time and materials was 1 US dollar for the Grossman-Roudner cone,
      20 US dollars for the cast, and 1,400 US dollars for the MRI. Using the mean and
      standard deviations of the measurements, a power analysis determined the number
      of subjects needed to detect a 5% change in volume. The number of subjects was
      multiplied by the price per test to determine relative cost. RESULTS: As compared
      with the cost for the Grossman-Roudner cone method, the cost for the volume
      measurements was 64 to 189 times more using the cast and 373 to 33,500 more using
      MRI. CONCLUSIONS: The Grossman-Roudner cone was clearly the most cost-effective
      method for determining breast volume changes in studies testing topical therapies
      to alter breast size.

PMID- 16411161
TI  - Regulation of two distinct alcohol oxidase promoters in the methylotrophic yeast
      Pichia methanolica.
AB  - In this study, two Pichia methanolica alcohol oxidase (AOD) promoters, P(MOD1)
      and P(MOD2), were evaluated in a promoter assay system utilizing the acid
      phosphatase (AP) gene from Saccharomyces cerevisiae (ScPHO5) as a reporter.
      Heterologous gene expression driven by the P(MOD1) and P(MOD2) promoters was
      found to be strong and tightly regulated by carbon source at the transcriptional
      level. P(MOD1) was induced not only by methanol but also by glycerol. P(MOD2) was
      induced only by methanol, although it was not repressed on the addition of
      glycerol to a methanol medium, suggesting that P(MOD2) is regulated in a manner
      distinct from that of other AOD-gene promoters. On the other hand, methanol and
      oxygen level-influenced gene expression mediated by P(MOD1) and P(MOD2). P(MOD1)
      expression was optimal at low methanol concentrations, whereas P(MOD2) was
      predominantly expressed at high methanol and high oxygen concentrations. Based on
      these results, both P(MOD2) and P(MOD1) should be useful tools for controlling
      heterologous gene expression in P. methanolica. In particular, it should be
      possible to differentially control the production phases of two heterologous
      proteins, using P(MOD1) and P(MOD2) in the same host cell and in the same flask.

PMID- 16411160
TI  - Discrimination of direction in fast frequency-modulated tones by rats.
AB  - Fast frequency modulations (FM) are an essential part of species-specific
      auditory signals in animals as well as in human speech. Major parameters
      characterizing non-periodic frequency modulations are the direction of frequency
      change in the FM sweep (upward/downward) and the sweep speed, i.e., the speed of
      frequency change. While it is well established that both parameters are
      represented in the mammalian central auditory pathway, their importance at the
      perceptual level in animals is unclear. We determined the ability of rats to
      discriminate between upward and downward modulated FM-tones as a function of
      sweep speed in a two-alternative-forced-choice-paradigm. Directional
      discrimination in logarithmic FM-sweeps was reduced with increasing sweep speed
      between 20 and 1,000 octaves/s following a psychometric function. Average
      threshold sweep speed for FM directional discrimination was 96 octaves/s. This
      upper limit of perceptual FM discrimination fits well the upper limit of
      preferred sweep speeds in auditory neurons and the upper limit of neuronal
      direction selectivity in the rat auditory cortex and midbrain, as it is found in
      the literature. Influences of additional stimulus parameters on FM discrimination
      were determined using an adaptive testing-procedure for efficient threshold
      estimation based on a maximum likelihood approach. Directional discrimination
      improved with extended FM sweep range between two and five octaves.
      Discrimination performance declined with increasing lower frequency boundary of
      FM sweeps, showing an especially strong deterioration when the boundary was
      raised from 2 to 4 kHz. This deterioration corresponds to a frequency-dependent
      decline in direction selectivity of FM-encoding neurons in the rat auditory
      cortex, as described in the literature. Taken together, by investigating
      directional discrimination of FM sweeps in the rat we found characteristics at
      the perceptual level that can be related to several aspects of FM encoding in the
      central auditory pathway.

PMID- 16411163
TI  - Non-invasive monitoring of renal oxygenation using BOLD-MRI: a reproducibility
      study.
AB  - Blood oxygenation level-dependent (BOLD) MRI was shown to allow non-invasive
      observation of renal oxygenation in humans. However, clinical applications of
      this type of functional MRI of the kidney are still limited, most likely because
      of difficulties in obtaining reproducible and reliable information. The aim of
      this study was to evaluate the reproducibility and robustness of a BOLD method
      applied to the kidneys and to identify systematic physiological changes
      potentially influencing the renal oxygenation of healthy volunteers. To measure
      the BOLD effect, a modified multi-echo data image combination (MEDIC) sequence
      was used to acquire 12 T2*-weighted images within a single breath-hold. Three
      identical measurements were performed on three axial and three coronal slices of
      right and left kidneys in 18 volunteers. The mean R2* (1/T2*) values determined
      in medulla and cortex showed no significant differences over three repetitions
      and low intra-subject coefficients of variation (CV) (3 and 4% in medulla and
      cortex, respectively). The average R2* values were higher in the medulla (16.15
      +/- 0.11) than in the cortex (11.69 +/- 0.18) (P < 0.001). Only a minor influence
      of slice orientation was observed. Mean R2* values were slightly higher (3%) in
      the left than in the right kidney (P < 0.001). Differences between volunteers
      were identified (P < 0.001). Part of these differences was attributable to age
      dependent R2* values, since these values increased with age when medulla (P <
      0.001, r = 0.67) or cortex (P < 0.020, r = 0.42) were considered. Thus, BOLD
      measurements in the kidney are highly reproducible and robust. The results allow
      one to identify the known cortico-medullary gradient of oxygenation evidenced by
      the gradient of R2* values and suggest that medulla is more hypoxic in older than
      younger individuals. BOLD-MRI is therefore a useful tool to study sequentially
      and non-invasively regional oxygenation of human kidneys.

PMID- 16411162
TI  - Isolation and characterization of promoters suitable for a multidrug-resistant
      marker CuYAP1 in the yeast Candida utilis.
AB  - The overexpression of CuYAP1 by the CuGAP1 promoter (Pgap) was recently shown to
      function as a drug-resistant selection marker for the industrially important
      yeast Candida utilis. In order to increase the efficiency of selection, we
      screened for promoters better than Pgap to express CuYAP1. Two restriction
      fragments, P2-1-2 (0.5 kbp) and P2-33-2 (1.4 kbp), gave higher cycloheximide
      resistance, and five- to 10-fold of the transformants were selectable by using
      these fragments. These promoters were found to be at the 5' of the ribosomal
      protein genes, RPL31 and RPL29, respectively. Interestingly, their transcription
      activity was less than one-tenth that of Pgap in the absence of cycloheximide.
      The transcription also increased by the addition of blasticidin S or hygromycin B
      and heat shock. These novel characteristics will be suitable for an economical
      marker of the recombinant cell. The DDBJ/EMBL/GenBank Accession Nos. for P2-1, P2
      33-2, RPL31 and RPL29 are AB206952, AB206953, AB208646 and AB208647,
      respectively.

PMID- 16411165
TI  - Effect of dose rate and mixtures of fungicides on selection for QoI resistance in
      populations of Plasmopara viticola.
AB  - Resistance to QoI fungicides (strobilurins, famoxadone and fenamidone) in
      populations of Plasmopara viticola (Berk & Curt) Berlese & de Toni developed soon
      after their introduction in France and Italy. Current resistance management
      strategies include limitation of the number of applications, use of mixtures and
      alternation of fungicides with different modes of action. The selection pressure
      resulting from QoI fungicides applied alone or in mixtures with non-QoI
      fungicides was investigated in whole plant experiments under controlled
      conditions. QoI-resistant populations of P. viticola gradually reverted to full
      sensitivity following consecutive transfers to untreated plants, suggesting that
      resistant phenotypes were less competitive than sensitive ones. When cycled on
      QoI-treated plants, reduction in sensitivity was greater for the QoI fungicide
      which had greater intrinsic activity on P. viticola. Sensitivity decreased at
      each subsequent cycle, resulting in almost full resistance after four
      generations. Mixture experiments indicated that selection pressure was affected
      most by the dose of the QoI fungicide and the nature of the partner fungicide.
      Folpet delayed selection pressure most effectively when it was associated with
      famoxadone or azoxystrobin. Mancozeb was least effective at reducing the rate of
      selection compared with the QoI alone, and fosetyl-aluminium was intermediate.
      Higher rates of selection were recorded when the dose of the QoI fungicide, solo
      or in a mixture, was increased from 1 to 4 microg ml(-1). Increasing the dose of
      the non-QoI partner fungicide in the mixture from 10 to 30 microg ml(-1) resulted
      in reduced selection pressure. These results suggest that the choice of the
      fungicide partner and its dosage in the mixture can significantly affect the
      success of QoI resistance management strategies under practical conditions.

PMID- 16411167
TI  - IR-SE and IR-MEMRI allow in vivo visualization of oscine neuroarchitecture
      including the main forebrain regions of the song control system.
AB  - Songbirds share with humans the capacity to produce learned vocalizations (song).
      Recently, two major regions within the songbird's neural substrate for song
      learning and production; nucleus robustus arcopallii (RA) and area X (X) are
      visualized in vivo using Manganese Enhanced MRI (MEMRI). The aim of this study is
      to extend this to all main interconnected forebrain Song Control Nuclei. The
      ipsilateral feedback circuits allow Mn2+ to reach all main Song Control Nuclei
      after stereotaxic injection of very small doses of MnCl2 (10 nl of 10 mM) into
      HVC of one and MAN (nucleus magnocellularis nidopallii anterioris) of the other
      hemisphere. Application of a high resolution (80 micron) Spin Echo Inversion
      Recovery sequence instead of conventional T1-weighted Spin Echo images improves
      the image contrast dramatically such that some Song Control Nuclei, ventricles,
      several laminae, fibre tracts and other specific brain regions can be discerned.
      The combination of this contrast-rich IR-SE sequence with the transsynaptic
      transport property of Manganese (Inversion Recovery based MEMRI (IR-MEMRI))
      enables the visualization of all main interconnected components of the Song
      Control System in telencephalon and thalamus.

PMID- 16411166
TI  - Analysis of lesion development during acute inflammation and remission in a rat
      model of experimental autoimmune encephalomyelitis by visualization of macrophage
      infiltration, demyelination and blood-brain barrier damage.
AB  - In vivo tracking of macrophage migration is feasible by labeling cells with ultra
      small particles of iron oxide (USPIO). It is demonstrated that it is possible to
      monitor distinct patterns of macrophage migration during the early states of
      inflammation in a rodent model of chronic relapsing experimental autoimmune
      encephalomyelitis (EAE). As previous MRI studies showed that EAE inflammation
      processes are clearly linked to macrophage infiltration in the brain, a
      longitudinal protocol for macrophage visualization was designed, where USPIOs
      were injected repeatedly during the acute phase of the disease, the remitting
      phase and the first relapse. In addition to USPIO-enhanced MRI, blood-brain
      barrier (BBB) damage, magnetization transfer ratios (MTRs) and neurological
      impairment were assessed as classical markers for central nervous system (CNS)
      inflammation and tissue damage. During the acute phase, animals showed severe
      paralysis of the hind paws, intense accumulation of macrophages in brain tissue
      and some diffuse patterns of BBB disruption. While USPIO-accumulation completely
      disappeared after the acute phase, residual damage of the BBB remained detectable
      in some lesions during the remitting phase. During the first relapse, the
      accumulation of USPIO-loaded cells was less pronounced but still detectable. The
      time course of MTR, which is used as a marker for myelin loss, was linked to the
      infiltration of macrophages during the acute phase.

PMID- 16411168
TI  - Interleaved snapshot echo planar imaging of mouse brain at 7.0 T.
AB  - Single-shot echo planar imaging (EPI) of a mouse brain at high field is very
      challenging. Large susceptibility-induced gradients affect much of the brain
      volume, causing severe image deformations and signal loss. Segmented EPI and
      other conventional multi-shot approaches alleviate these problems but suffer from
      lower temporal resolution and motion artifacts. We demonstrate that interleaved
      snapshot EPI represents a simple and robust alternative approach and one that is
      particularly suitable for high-field T2*-weighted functional imaging of a mouse
      brain. Similarly to segmented multi-shot techniques, it significantly reduces the
      susceptibility-related artifacts. At the same time, it preserves the high
      temporal resolution and the snapshot capability of a conventional EPI by
      acquiring entire image within a single TR period. We discuss implementation
      details of the interleaved snapshot EPI sequence and the trade-offs involved
      between the imaging efficiency, the number of interleaved excitation-acquisition
      blocks and the artifact reduction. To document the sequence utility, murine brain
      in vivo imaging with the interleaved snapshot EPI method was compared with a
      conventional EPI. We found that at least five interleaved blocks were necessary
      to restore the signal in most cortical areas. We also show that a standard global
      shimming procedure provides sufficient homogeneity for multi-slice interleaved
      snapshot EPI acquisition. In contrast, the conventional EPI of comparable image
      quality would be limited to a single slice with highly optimized local shim.
      Finally, an in vitro comparison with turbo FLASH acquisition shows the
      interleaved snapshot EPI to have superior time resolution and signal-to-noise
      ratio.

PMID- 16411169
TI  - Metabolite identification in human liver needle biopsies by high-resolution magic
      angle spinning 1H NMR spectroscopy.
AB  - High-resolution magic angle spinning (HR-MAS) 1H NMR spectroscopy of intact human
      liver needle biopsies has not been previously reported. HR-MAS NMR spectra
      collected on 17 specimens with tissue amounts between approximately 0.5 and 12 mg
      showed very good spectral resolution and signal-to-noise ratios. One-dimensional
      1H spectra revealed many intense signals corresponding to cellular metabolites.
      In addition, some high molecular weight metabolites, such as glycogen and mobile
      fatty acids, could be observed in some spectra. Resonance assignments for 22
      metabolites were obtained by combining the analysis of three different types of
      1D 1H spectral editing, such as T2 filtering or the nuclear Overhauser effect and
      2D TOCSY and 13C-HSQC spectra. Biochemical stability of the liver tissue during
      up to 16 h of magic angle spinning at 277 K was studied. Biochemical trends
      corresponding to the different pathologies were observed, involving free
      fragments of lipids among other metabolites. NMR signal intensity ratios can be
      useful for discrimination among non-pathological, hepatitis C affected and
      cirrhotic liver tissues. Overall, this work demonstrates the applicability of HR
      MAS NMR spectroscopy to the biochemical characterization of needle biopsies of
      the human liver.

PMID- 16411170
TI  - The role of vessel maturation and vessel functionality in spontaneous
      fluctuations of T2*-weighted GRE signal within tumors.
AB  - Acute hypoxia (transient cycles of hypoxia-reoxygenation) is known to occur in
      solid tumors and is generally believed to be caused by tumor blood flow
      instabilities. It was recently demonstrated that T2*-weighted (T2*w) gradient
      echo (GRE) MRI is a powerful non-invasive method for investigating periodic
      changes in tumor pO2 and blood flow associated with acute hypoxia. Here, the
      possible correlation between tumor vessel immaturity, vessel functionality and
      T2*w GRE signal fluctuations was investigated. Intramuscularly implanted FSa II
      fibrosarcoma-bearing mice were imaged at 4.7 T. Maps of spontaneous fluctuations
      of MR signal intensity in tumor tissue during air breathing were obtained using a
      T2*w GRE sequence. This same sequence was also employed during air-5% CO2
      breathing (hypercapnia) and carbogen breathing (hypercapnic hyperoxia) to obtain
      parametric maps representing vessel maturation and vessel function, respectively.
      Vascular density, vessel maturation and vessel perfusion were also assessed
      histologically by using CD31 labeling, alpha-smooth muscle actin immunoreactivity
      and Hoechst 33242 labeling, respectively. About 50% of the tumor fluctuations
      occurred in functional tumor regions (responsive to carbogen) and 80% occurred in
      tumor regions with immature vessels (lack of response to hypercapnia). The
      proportion of hypercapnia-responsive voxels were found to be twice as great in
      fluctuating than in non-fluctuating tumor areas (P: 0.22 vs 0.13). Similarly, the
      proportion of functional voxels was somewhat greater in fluctuating tumor areas
      (P: 0.54 vs 0.43). The mean values of MR signal changes during hypercapnia (VD)
      and during carbogen breathing (VF) (significant voxels only) were also larger in
      fluctuating than in non-fluctuating tumor areas (P < 0.05). This study
      demonstrated that adequate vessel functionality and advanced vessel maturation
      could explain at least in part the occurrence of spontaneous T2*w GRE signal
      fluctuations. Functionality and maturation are not required for signal
      fluctuations, however, because a large fraction of fluctuations could still occur
      in non-perfused and/or immature vessels.

PMID- 16411171
TI  - Enhanced funding of pharmacoepidemiology through patenting the disclosure of
      adverse event information.
AB  - PURPOSE: Known drug adverse events have been estimated to be between the 4th and
      6th leading cause of death in the US (1). There are currently insufficient funds
      to perform the quantity and quality of studies necessary to ensure all drug
      adverse events are discovered in a timely fashion. METHODS/RESULTS: One approach
      to attract capital for pharmacoepidemiology studies is to patent the discoveries
      from the studies. Potential investors, whether executives of branded
      pharmaceutical companies or not, will consider funding pharmacoepidemiology
      studies if they can expect to receive competitive returns on their investments.
      Pharmacoepidemiolists who desire to patent their discoveries should seek novel
      drug-drug and drug-food interactions or negative interactions between drugs and
      certain phenotypes, genotypes or preexisting comorbidities. CONCLUSION: These
      discoveries can lead to safer, and patentable, use of the drug by avoiding these
      interactions.

PMID- 16411172
TI  - Cyanoacetic acid hydrazones of 3-(and 4-)acetylpyridine and some derived ring
      systems as potential antitumor and anti-HCV agents.
AB  - Two new acetylpyridinehydrazones derived from cyanoacetic acid hydrazide have
      been synthesized namely: cyanoacetic acid (1-pyridin-3 or 4-yl-ethylidene)
      hydrazides (1a,b). and some derived ring systems: 2-imino or 2-oxo-2H-chromenes
      (2a,b and 3a,b), substituted 2-thioxo-2,3-dihydrothiazoles (4a-d), substituted 2
      thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (5a-d), substituted
      dihydrothiazoles (7a,b), and substituted 2-oxo-1,2-dihydropyridines (8a-d and
      9a,b). Fifteen compounds were evaluated for their anticancer activity using the
      USA-NCI in-vitro screening program. Among the tested compounds, 8d exhibited a
      high value of percent tumor growth inhibition at concentrations of 10(-5) to 10(
      7) M in all cancer cell lines, while 8b exhibited a significant value of percent
      tumor growth inhibition at concentration <10(-8 )M against non-small cells lung
      HOP-92. In addition, nine compounds were investigated for their in-vitro effect
      on the replication of hepatitis-C virus (HCV) in HepG2 hepatocellular carcinoma
      cell line infected with the virus using the reverse transcription polymerase
      chain reaction technique. Six compounds were capable of inhibiting the
      replication of both the HCV RNA (+)- and (-)-strands at 5-100 microg/mL
      concentration range. The activity order was 7b > 1b = 3a > 4c > 7a > 5c.

PMID- 16411173
TI  - Synthesis and biological evaluation of some pyrazolinylpyridines and
      pyrazolylpyridines.
AB  - Various new 2-(1'-acetyl-5'-substituted-aryl-2'-pyrazolin-3'-yl)aminopyridines
      (3a-3e) and 2-(1'-phenyl 5'-substituted aryl-2'-pyrazol-3'-yl)aminopyridines (4a
      4e) have been derived from 2-(substituted benzylidenylacetyl)aminopyridines (2a
      2e). The structure of these compounds have been elucidated by elemental and
      spectral (IR, 1H-NMR, mass) analysis. Furthermore, above said compounds were
      evaluated for their insecticidal, antifungal, and antibacterial activities.
      Compound 4b 2-[1'-phenyl-5'-(o-chlorophenyl)-2'-pyrazol-3'-yl]aminopyridine, when
      compared for insecticidal and antifungal activities with parathion and
      fluconazole, respectively, was found to be the most potent one in this series. It
      also possessed remarkable antibacterial properties.

PMID- 16411174
TI  - Synthesis of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid
      derivatives of potential anti-inflammatory activity.
AB  - A series of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid
      derivatives 4-10 were synthesized by rearrangement of 4-(3-pyridyl)-hydrazono-2
      phenyl-2-oxazolin-5-one 3 in the presence of different nucleophiles to afford
      derivatives 4, 7, and 8, while hydroxamic acid derivative 6 was prepared from
      reaction of methyl ester 4 with hydroxylamine hydrochloride. Semicarbazide 9 and
      thiosemicarbazide 10, derivatives of the 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole
      3-carboxylic acid, were synthesized via hydrazide 8 with potassium cyanate and
      appropriate isothiocyanate, respectively. The structures of the synthesized
      compounds were confirmed by elemental analyses, IR, (1)H-NMR, and mass spectra.
      The results of the anti-inflammatory activity of the synthesized derivatives
      showed that most of the tested compounds 4-10 showed significant inhibition
      against carrageenan-induced rat paw edema in albino rats. Derivatives 4 and 8
      showed promising results and were found to be equipotent or more potent than
      Indomethacin and Celecoxib as reference drugs at two dose levels, 5 and 10 mg/kg,
      and they have no ulcerogenic activity.

PMID- 16411175
TI  - 4-Chloro-2,2-disubstituted chromen-3-carboxaldehyde: synthesis of some fused
      polycyclic heterocycles as anti-inflammatory, analgesic, anticonvulsant, and
      antiparkinsonian agents.
AB  - Some new aldazino 4, pyrazolo 5, thieno 8, and thiooxopyrimidino chromenes 10
      were prepared via reaction of the corresponding beta-chlorocarboxaldehyde 3 with
      hydrazine hydrate, mercaptoacetic acid, and thiourea, respectively. Wherever, 4
      chlorochromene derivatives 2 along with 4-chlorochromen-3-carboxaldehyde
      derivatives 3 were prepared from the corresponding ketone 1 with Vilsmeier-Haack
      reagent. Some of the new products showed good anti-inflammatory, analgesic,
      anticonvulsant, and antiparkinsonian activities comparable to indomethacin,
      diclofenace, carbamazepine, and benztropine.

PMID- 16411176
TI  - Amidrazones as precursors of biologically active compounds--synthesis of
      diaminopyrazoles for evaluation of anticancer activity.
AB  - The regioselectivity of coupling phenyl isocyanate to 3-(2-acylhydrazino)-3
      aminopropenenitriles and ethyl 3-(2-acylhydrazino)-3-aminopropenoates as simple
      access to aminopyrazole derivatives, endowed with potential antitumoral activity,
      is reported. 3-(2-Acylhydrazino)-3-aminopropenenitriles react with phenyl
      isocyanate to afford 3-amino-3-(2-acylhydrazino)-2-phenylaminocarbonyl-2
      propenenitriles. These key intermediates were cyclized into 3,5-diaminopyrazole-4
      carboxamide derivatives. Preliminary results of poor antiproliferative activities
      of these compounds are also reported.

PMID- 16411177
TI  - Masking selected sequence variation by incorporating mismatches into melting
      analysis probes.
AB  - Hybridization probe melting analysis can be complicated by the presence of
      sequence variation (benign polymorphisms or other mutations) near the targeted
      mutation. We investigated the use of "masking" probes to differentiate alleles
      with similar probe melting temperatures. Selected sequence variation was masked
      by incorporating mismatches (deletion, unmatched nucleotide, or universal base)
      into hybridization probes at the polymorphic location. Such masking probes create
      a probe/target mismatch with all possible alleles at the selected polymorphic
      location. Any allele with additional variation at another site is identified by a
      lower probe melting temperature than alleles that vary only at the masked
      position. This "masking technique" was applied to RET protooncogene and HPA6
      mutation detection using unlabeled hybridization probes, a saturating dsDNA dye,
      and high-resolution melting analysis. Masking probes clearly distinguished all
      targeted mutations from polymorphisms when at least 1 base pair (bp) separated
      the mutation from the masked variation. We were able to mask polymorphisms
      immediately adjacent to mutations, except in certain cases, such as those
      involving single-base deletion probes when both adjacent positions had the same
      polymorphic nucleotides. The masking probes can also localize mutations to
      specific codons or nucleotide positions. Masking probes can simplify melting
      analysis of complex regions and eliminate the need for sequencing.

PMID- 16411178
TI  - Is selective mutism associated with deficits in memory span and visual memory?:
      An exploratory case-control study.
AB  - Our main aim in this study was to explore the association between selective
      mutism (SM) and aspects of nonverbal cognition such as visual memory span and
      visual memory. Auditory-verbal memory span was also examined. The etiology of SM
      is unclear, and it probably represents a heterogeneous condition. SM is
      associated with language impairment, but nonspecific neurodevelopmental factors,
      including motor problems, are also reported in SM without language impairment.
      Furthermore, SM is described in Asperger's syndrome. Studies on nonverbal
      cognition in SM thus merit further investigation. Neuropsychological tests were
      administered to a clinical sample of 32 children and adolescents with SM (ages 6
      17 years, 14 boys and 18 girls) and 62 nonreferred controls matched for age,
      gender, and socioeconomic status. We used independent t-tests to compare groups
      with regard to auditory-verbal memory span, visual memory span, and visual memory
      (Benton Visual Retention Test), and employed linear regression analysis to study
      the impact of SM on visual memory, controlling for IQ and measures of language
      and motor function. The SM group differed from controls on auditory-verbal memory
      span but not on visual memory span. Controlled for IQ, language, and motor
      function, the SM group did not differ from controls on visual memory. Motor
      function was the strongest predictor of visual memory performance. SM does not
      appear to be associated with deficits in visual memory span or visual memory. The
      reduced auditory-verbal memory span supports the association between SM and
      language impairment. More comprehensive neuropsychological studies are needed.

PMID- 16411179
TI  - Impact of voice on emotional judgment of faces: an event-related fMRI study.
AB  - Emotional information can be conveyed by various means of communication, such as
      propositional content, speech intonation, facial expression, and gestures. Prior
      studies have demonstrated that inputs from one modality can alter perception in
      another modality. To evaluate the impact of emotional intonation on ratings of
      emotional faces, a behavioral study first was carried out. Second, functional
      magnetic resonance (fMRI) was used to identify brain regions that mediate
      crossmodal effects of emotional prosody on judgments of facial expressions. In
      the behavioral study, subjects rated fearful and neutral facial expressions as
      being more fearful when accompanied by a fearful voice as compared to the same
      facial expressions without concomitant auditory stimulus, whereas no such
      influence on rating of faces was found for happy voices. In the fMRI experiment,
      this shift in rating of facial expressions in presence of a fearfully spoken
      sentence was correlated with the hemodynamic response in the left amygdala
      extending into the periamygdaloid cortex, which suggests that crossmodal effects
      on cognitive judgments of emotional information are mediated via these neuronal
      structures. Furthermore, significantly stronger activations were found in the mid
      portion of the right fusiform gyrus during judgment of facial expressions in
      presence of fearful as compared to happy intonations, indicating that enhanced
      processing of faces within this region can be induced by the presence of threat
      related information perceived via the auditory modality. Presumably, these
      increased extrastriate activations correspond to enhanced alertness, whereas
      responses within the left amygdala modulate cognitive evaluation of emotional
      facial expressions.

PMID- 16411180
TI  - Role of P16(INK4a) expression in identifying CIN2 or more severe lesions among
      HPV-positive patients referred for colposcopy after abnormal cytology.
AB  - BACKGROUND: p16 is strongly overexpressed in dysplastic cervical cells because of
      the transforming activity of the E7 oncogene of all high-risk human
      papillomavirus (HR-HPV) types and may be easily revealed by immunochemistry: p16
      may, therefore, be considered a surrogate marker for the activated oncogene
      expression of HR-HPV in dysplastic cervical cells. METHODS: HPV and p16(INK4a)
      testing were performed in a consecutive series of 283 patients with abnormal
      cytology referred to colposcopy assessment or follow-up. Triage of patients to
      colposcopy by HPV or HPV and p16 testing was simulated, and the relative
      sensitivity, specificity, and positive predictive value (PPV) of HPV and p16
      testing for > CIN2 lesions was determined as well as the cost balance of the two
      triage types. RESULTS: Compared to current protocol, triage by HPV testing
      reduced the number of colposcopies by 44.2%, but also reduced the > CIN2
      detection rate by 10.7%, and was associated with a cost of euro 54.16 per
      assessed woman and of euro 613.20 per > CIN2 detected. Compared with current
      protocol, triage by HPV and p16 testing combined reduced the number of
      colposcopies by 73.1%, but reduced > CIN2 detection rate by 21.5%, and was
      associated with a cost of euro 54.73 per woman assessed and of euro 704.09 per >
      CIN2 detected. CONCLUSIONS: Triage by HPV and p16 improves considerably the PPV
      of diagnostic assessment, but decreases > CIN2 detection rate, and is associated
      with substantially higher costs. Further decrease of molecular immunochemistry
      testing due to technological progress may allow HPV and p16 testing to become a
      cost effective procedure in the future.

PMID- 16411181
TI  - Editorial.

PMID- 16411182
TI  - Gonadal hormone modulation of hippocampal neurogenesis in the adult.
AB  - Gonadal hormones modulate neurogenesis in the dentate gyrus (DG) of adult rodents
      in complex ways. Estradiol, the most potent estrogen, initially enhances and
      subsequently suppresses cell proliferation in the dentate gryus of adult female
      rodents. Much less is known about how estradiol modulates neurogenesis in the
      adult male rodent; however, recent evidence suggests that estradiol may have a
      moderate effect on cell proliferation but enhances cell survival in the DG of
      newly synthesized cells but only when estradiol is administered during a specific
      stage in the cell maturation cycle in the adult male rodent. Testosterone likely
      plays a role in adult neurogenesis, although there have been no direct studies to
      address this. However, pilot studies from our laboratory suggest that
      testosterone up-regulates cell survival but not cell proliferation in the DG of
      adult male rats. Progesterone appears to attenuate the estradiol-induced
      enhancement of cell proliferation. Neurosteroids such as allopregnalone decrease
      neurogenesis in adult rodents, while pregnancy and motherhood differentially
      regulate adult neurogenesis in the adult female rodent. Very few studies have
      investigated the effects of gonadal hormones on male rodents; however, studies
      have indicated that there is a gender difference in the response to hormone
      regulated hippocampal neurogenesis in the adult. Clearly, more work needs to be
      done to elucidate the effects of gonadal hormones on neurogenesis in the DG of
      both male and female rodents.

PMID- 16411183
TI  - uCyt+/ImmunoCyt in the detection of recurrent urothelial carcinoma: an update on
      1991 analyses.
AB  - BACKGROUND: The authors provide an update on the clinical value and role of the
      uCyt+/ImmunoCyt test as a noninvasive tool for the detection of recurrent
      urothelial carcinoma. METHODS: Between January 2002 and October 2004, 942
      patients (mean age, 72.6 yrs; range, 32-87 yrs) were enrolled in this prospective
      study. These patients mostly had been followed for superficial urothelial
      carcinoma (UC) confined to the mucosa and lamina propria (pathologic tumor [pT]
      classification pTa, pT1, and pTis [carcinoma in situ]) for a mean of 15.62 months
      (range, 4-28 mos). Voided urinary cytology and the uCyt+/ImmunoCyt test for all
      patients were performed on liquid-based cytology slides. Patients underwent
      subsequent cystoscopy when cytology or uCyt+/ImmunoCyt results were positive and
      when they underwent biopsy evaluation of any suspicious lesion. Altogether, 1991
      uCyt+/ImmunoCyt analyses were performed. RESULTS: Two hundred ninety-eight
      patients who had adequate samples available were diagnosed with histologically
      proven UC. The sensitivity of cytology increased from 8.3% for Grade 1 tumors to
      75.3% for Grade 3 tumors; whereas, with the uCyt+/ImmunoCyt, the sensitivity was
      79.3% for Grade 1 tumors, 84.1% for Grade 2 tumors, and 92.1% for Grade 3 tumors.
      For cytology and uCyt+/ImmunoCyt combined, the sensitivity was 79.3% for Grade 1
      tumors, 90.9% for Grade 2 tumors, and 98.9% for Grade 3 tumors. CONCLUSIONS: The
      current data confirmed the clinical usefulness of the uCyt+/ImmunoCyt test in the
      follow-up of patients with recurrent UC. Used as a noninvasive tool, cytology
      escorted by uCyt+/ImmunoCyt may reduce the morbidity and cost of follow-up for
      patients who have a low risk of recurrence while avoiding superfluous cystoscopic
      examinations. However, additional studies will be necessary to establish and
      compare the morbidity and cost of each method.

PMID- 16411184
TI  - Retrograde amnesia following hippocampal lesions in the shock-probe conditioning
      test.
AB  - The present experiment examined the role of the hippocampal formation (HPC) in
      long-term memory of an association between an object and a fear-eliciting event.
      Rats either received sham or neurotoxic lesions of the HPC 1 or 14 days after
      learning that contacting a wire-wrapped probe (i.e., object) elicits a shock.
      After recovery from the surgery, rats were re-exposed to the wire-wrapped probe
      and burying and avoidance of the probe were assessed and used as memory and fear
      indices. Regardless of the learning-to-surgery interval, the rats with
      hippocampal lesions buried and avoided the probe significantly less than sham
      rats and no more than rats that never experienced shock from the probe. These
      findings suggest that the lesions caused severe retrograde amnesia and that the
      HPC has a long-lasting role in memory of a discrete stimulus associated with a
      fear-eliciting event.

PMID- 16411185
TI  - Generalized anxiety disorder severity scale (GADSS): a preliminary validation
      study.
AB  - To assist researchers and clinicians in primary care with assessment and
      treatment of generalized anxiety disorder (GAD), we developed a simple
      standardized instrument, similar to the Panic Disorder Severity Scale.
      Independent evaluators used the six-item Generalized Anxiety Disorder Severity
      Scale (GADSS) to conduct telephone assessments of 330 patients from four primary
      care facilities with DSM-IV diagnoses of GAD and/or panic disorder who were
      participating in a study of the effectiveness of collaborative care treatment.
      Participants were also evaluated at a 12-month follow-up. Internal consistency,
      convergent and discriminant validity, and sensitivity to change were determined.
      The GADSS had high internal consistency, and showed good validity and sensitivity
      to change. Change in GADSS scores discriminated between two different treatment
      strategies. GADSS is a simple, efficient way to rate severity over the telephone
      in patients with established diagnoses of GAD.

PMID- 16411186
TI  - Stabilization of unusual structures in peptides using alpha,beta
      dehydrophenylalanine: crystal and solution structures of Boc-Pro-DeltaPhe-Val
      DeltaPhe-Ala-OMe and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe.
AB  - The structures of two dehydropentapeptides, Boc-Pro-DeltaPhe-Val-DeltaPhe-Ala-OMe
      (I) and Boc-Pro-DeltaPhe-Gly-DeltaPhe-Ala-OMe (II) (Boc: t-butoxycarbonyl), have
      been determined by nuclear magnetic resonance (NMR), circular dichroism (CD), and
      X-ray crystallographic studies. The peptide I assumes a S-shaped flat beta-bend
      structure, characterized by two partially overlapping type II beta-bends and
      absence of a second 1 <-- 4 (N4--H . . . O1') intramolecular hydrogen bond. This
      is in contrast to the generally observed 3(10)-helical conformation in peptides
      with DeltaPhe at alternate positions. This report describes the novel
      conformation assumed by peptide I and compares it with that of the conserved tip
      of the V3 loop of the HIV-1 envelope glycoprotein gp120 (sequence, G:P319 to
      F:P324, PDB code 1ACY). The tip of the V3 loop also assumes a S-shaped
      conformation with Arg:P322, making an intramolecular side-chain-backbone
      interaction with the carbonyl oxygen of Gly:P319. Interestingly, in peptide I,
      C(gamma)HVal(3) makes a similar side-chain-backbone C--H . . . O hydrogen bond
      with the carbonyl oxygen of the Boc group. The observed overall similarity
      indicates the possible use of the peptide as a viral antagonist or synthetic
      antigen. Peptide II adopts a unique turn followed by a 3(10)-helix. Both peptides
      I and II are classical examples of stabilization of unusual structures in
      oligopeptides.

PMID- 16411187
TI  - The 11-mer repeats of human alpha-synuclein in vesicle interactions and lipid
      composition discrimination: a cooperative role.
AB  - alpha-Synuclein is a protein abundant in presynaptic terminals in the brain. The
      N-terminal region of the sequence contains an imperfect 11-residue periodicity
      also found in A-class apolipoproteins and able to fold into an amphipathic helix.
      Here, the ability of three fragments of the protein, which include one, two, and
      all repeats, respectively, to bind to vesicles of different phospholipid
      composition is described. The results suggest a cooperative action of the repeats
      in selecting target membranes for interaction based on their lipid composition.
      This deduction is possibly related to the physiological role of the protein,
      which is still poorly understood.

PMID- 16411188
TI  - Characterization of beta-turn and Asx-turns mimicry in a model peptide:
      stabilization via C--H . . . O interaction.
AB  - The chemical synthesis and single-crystal X-ray diffraction analysis of a model
      peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an
      amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the
      analysis of its molecular structure revealed the existence of a distinct
      conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr
      residues occupy the left- and right-corner positions. The main-chain torsion
      angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees
      , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees
      conformations, respectively, in conjunction with a gauche- disposition of the
      obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the
      newly described beta-turn- and Asx-turns-like topology. The preferred molecular
      structure is suggested to be stabilized by an effective nonconventional main
      chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond.
      Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded
      ring is essentially similar to the one perceived for a classical beta-turn and
      the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering
      the signs as well as magnitudes of the backbone torsion angles and the
      orientation of the central peptide bond, the overall mimicked topology resembles
      the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in
      high-resolution X-ray elucidated protein structures revealed the novel topology
      prevalence in functional proteins (unpublished). In view of indubitable
      structural as well as functional importance of nonconventional interactions in
      bioorganic and biomacromolecules, we intend to highlight the participation of Thr
      CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in
      peptides and proteins.

PMID- 16411189
TI  - Finlay-Marks (SEN) syndrome: a sporadic case and the delineation of the syndrome.

PMID- 16411190
TI  - A family with features overlapping Okihiro syndrome, hemifacial microsomia and
      isolated Duane anomaly caused by a novel SALL4 mutation.
AB  - The SALL4 gene encodes a putative zinc finger transcription factor and is located
      on chromosome 20q13.13-13.2. Mutations in SALL4 have been identified in patients
      with Okihiro syndrome, which is characterized by radial ray anomalies associated
      with a Duane anomaly. Here, we report an unusual family in which affected persons
      show an extremely variable phenotype consistent with either Okihiro syndrome,
      hemifacial microsomia, or isolated Duane anomaly. A novel nonsense mutation in
      the SALL4 gene was detected in all affected family members and obligate carriers.
      This mutation is located in exon 3, only 29 bp 5' of the most 3' intron, and
      would therefore be expected to escape the nonsense mediated mRNA decay pathway,
      which might explain the phenotypic variability and mild degree of limb
      involvement.

PMID- 16411192
TI  - Karyotype-phenotype analysis and molecular delineation of a 3p26 deletion/8q24.3
      duplication case with a virtually normal phenotype and mild cognitive deficit.

PMID- 16411191
TI  - Shprintzen-Goldberg omphalocele syndrome: a new patient with an expanded
      phenotype.
AB  - Shprintzen and Goldberg [1979] described a new autosomal dominant syndrome
      characterized by omphalocele, scoliosis, pharyngeal and laryngeal hypoplasia,
      mild dysmorphic face, and learning disabilities. This condition was described in
      a father and three daughters, one of whom died in infancy, probably of airway
      narrowing. Here, we report on a second observation of this syndrome in a 6-year
      old patient. In our case, omphalocele, imperforate anus, and feeding impairment
      were the main clinical problems in the neonatal period. Scoliosis appeared during
      the fourth year of age. The facial appearance is similar to the original patients
      and additional clinical findings are described which expand the phenotypic
      spectrum.

PMID- 16411193
TI  - Novel clinical features in a child with partial deletion of chromosome 11
      [del(11)(q24.2)]: further evidence for phenotypic heterogeneity.

PMID- 16411194
TI  - Complementary and alternative medicine in pediatric oncology: availability and
      institutional policies in Canada--a report from the Children's Oncology Group.
AB  - Complementary and alternative medicine (CAM) is used frequently by pediatric
      oncology patients. A survey exploring the institutional practices and policies
      surrounding CAM use in pediatric oncology patients was completed by 17 pediatric
      hematology/oncology centers in Canada. We found that CAM was offered in only 18%
      of the institutions, but 94% of the communities. Only 6% of oncology divisions
      made direct referrals to community CAM providers, and only 20% of the centers had
      policies regarding use of CAM therapies for their patients. Despite published
      widespread use of CAM therapies, our study demonstrates that institutional CAM
      resources and policies on CAM are present in much lower proportions.

PMID- 16411195
TI  - Hybrid chemotherapy in two children with acute leukemia of ambiguous lineage.

PMID- 16411196
TI  - Differential impairment of the sudomotor and nociceptor axon-reflex in diabetic
      peripheral neuropathy.
AB  - It is not known whether C-fiber functional subclasses are differentially affected
      by diabetes mellitus or whether the patterns of C-fiber dysfunction are different
      between type 1 and type 2 diabetes. We therefore examined efferent sympathetic
      sudomotor and primary afferent nociceptor C-fiber function in diabetic patients.
      Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses.
      The nociceptor (flare) response was measured using a laser Doppler device. The
      sudomotor response was quantified with silastic imprints. The nociceptor C-fiber
      mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but
      was similar to controls in type 1 diabetic patients. The sympathetic C-fiber
      mediated responses, including sweat volume (P < 0.05) and the number of activated
      sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There
      also was a trend toward a larger axon-reflex sweat area in patients with type 1
      diabetes (P = 0.09). No differences in these sweat responses were found in
      patients with type 2 diabetes compared to controls. These findings suggest that
      the functional abnormalities in diabetic peripheral neuropathy are not
      homogeneous and that C-fiber subclasses are differentially affected in type 1 and
      2 diabetes mellitus.

PMID- 16411197
TI  - Temporary diabetes mellitus secondary to a primary pancreatic Burkitt lymphoma.
AB  - Primary pancreatic lymphoma (PPL) is a rare form of extranodal lymphoma. So far,
      only in adults has a coincidence with diabetes mellitus (DM) been described. We
      report a nearly 9-year-old German boy presenting with a Burkitt lymphoma
      associated with a temporary insulin-dependent DM and exocrine insufficiency of
      the pancreas. After the patient went into remission, a spontaneous recovery of
      the endocrine pancreatic function was observed. On immunophenotyping, the
      lymphoma cells revealed expression of FasL suggesting a potentially apoptotic
      effect on pancreatic tissue. Beta cell impairment may have been caused by FasL
      resembling autoimmune diabetes.

PMID- 16411198
TI  - Effective treatment of kaposiform hemangioendotheliomas associated with Kasabach
      Merritt phenomenon using four-drug regimen.
AB  - We report a case of a 6-month-old girl suffering from a kaposiform
      hemangioendothelioma of the chest wall, associated with Kasabach-Merritt
      phenomenon. Despite rapid intervention with cortisone and interferon alpha the
      tumor led to a life-threatening clinical condition with progressive growth and
      consumption coagulopathy under therapy. Because therapy for kaposiform
      hemangioendotheliomas with a single anti-angiogenic or anti-proliferative agent
      has not been reported to be very successful, we administered vincristine,
      combined with cyclophosphamide, actinomycin D, and methotrexate in a critically
      ill patient. After six cycles of the applied four-drug regiment, the infant was
      in remission, which has been maintained for 5 months since stopping therapy.

PMID- 16411199
TI  - Langerhans cell histiocytosis infiltration into pancreas and kidney.
AB  - An 18-month-old male presented with a swelling of the neck for 2 months. A
      presumptive diagnosis of Langerhans cell histiocytosis (LCH) was made on fine
      needle aspiration cytology from the lymph node. The child received chemotherapy.
      He remained well for around 10 months, when he represented with loose stools,
      cough, and respiratory distress. His condition deteriorated over a few hours
      culminating in death. A partial autopsy revealed LCH infiltration in liver,
      pancreas, and kidneys along with bronchopneumonia. The pancreatic and renal
      infiltration by LCH is extremely rare.

PMID- 16411200
TI  - Characterization of mosaic supernumerary ring chromosomes by array-CGH: segmental
      aneusomy for proximal 4q in a child with tall stature and obesity.
AB  - We report on a 6-year-old girl with developmental delay, tall stature, and
      obesity. G-banded chromosome analysis revealed mosaicism for one to three small
      de novo rings in 82% of peripheral lymphocytes. Fluorescence in situ
      hybridization (FISH) studies and metaphase comparative genomic hybridization
      (CGH) demonstrated that the rings were derived from 4q10-4q13. A higher
      resolution investigation was initiated using array-CGH analysis and revealed a
      gain of 11 adjacent clones spanning a 16 Mb region at 4q11-q13.2 and including
      the insulin-like growth factor binding protein 7 (IGFBP7) gene. This finding
      suggests that postnatal overgrowth observed in our patient might be related to a
      dosage effect of the IGFBP7 gene.

PMID- 16411201
TI  - Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven
      families with premature chromatid separation (PCS) syndrome.
AB  - Cancer-prone syndrome of premature chromatid separation (PCS syndrome) with
      mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder
      characterized by growth retardation, microcephaly, childhood cancer, premature
      chromatid separation of all chromosomes, and mosaicism for various trisomies and
      monosomies. Biallelic BUB1B mutations were recently reported in five of eight
      families with MVA syndrome (probably identical to the PCS syndrome). We here
      describe molecular analysis of BUB1B (encoding BubR1) in seven Japanese families
      with the PCS syndrome. Monoallelic BUB1B mutations were found in all seven
      families studied: a single-base deletion (1833delT) in four families; and a
      splice site mutation, a nonsense mutation, and a missense mutation in one family
      each. Transcripts derived from the patients with the 1833delT mutation and the
      splice site mutation were significantly reduced, probably due to nonsense
      mediated mRNA decay. No mutation was found in the second alleles in the seven
      families studied, but RT-PCR of BUB1B and Western blot analysis of BubR1
      indicated a modest decrease of their transcripts. BubR1 in the cells from two
      patients showed both reduced protein expression and diminished kinetochore
      localization. Their expression level of p55cdc, a specific activator of anaphase
      promoting complex, was normal but its kinetochore association was abolished.
      Microcell-mediated transfer of chromosome 15 (containing BUB1B) into the cells
      restored normal BubR1 levels, kinetochore localization of p55cdc, and the normal
      responses to colcemid treatment. These findings indicate the involvement of BubR1
      in p55cdc-mediated mitotic checkpoint signaling, and suggest that >50% decrease
      in expression (or activity) of BubR1 is involved in the PCS syndrome.

PMID- 16411202
TI  - Yellow teeth, seizures, and mental retardation: a less severe case of
      Kohlschutter-Tonz syndrome.
AB  - We describe an 11-year-old boy with hypoplastic amelogenesis imperfecta, yellow
      teeth, seizures, and developmental delay, which are the hallmarks of Kohlschutter
      Tonz syndrome. Compared to other reported cases of the syndrome, our patient had
      less severe developmental delay. Also, spasticity and loss of mental capacity
      should not be considered obligatory manifestations of the syndrome because they
      are not present in half of reported patients, as well as in our family. Origin of
      the parents of our patient from neighboring villages supports autosomal recessive
      inheritance of Kohlschutter-Tonz syndrome.

PMID- 16411203
TI  - Two cases of partial trisomy 21 (pter-q22.1) without the major features of Down
      syndrome.
AB  - We report two cases of partial trisomy 21 with clinical features distinct from
      Down syndrome (DS). These patients presented with moderate mental retardation and
      short stature, but the typical facial appearance of DS was not observed. Each
      patient had a similarly sized extra chromosome 21. We performed FISH analysis to
      examine whether deletions of reported approximately 5 Mb DS critical region
      (DSCR) might be associated with unusual clinical features in these cases. The
      results showed that each of their extra chromosomes 21 contained a distal part of
      chromosome 3p or 14q at the telomeric region of chromosome 21q. The translocation
      breakpoint of 21q for each patient was located on the centromeric side of DSCR
      (DSCR was deleted) and the sizes of partial trisomy 21 in respective patients are
      approximately 34.5 (21pter-q22.12) and approximately 33.0 Mb (21pter-q22.11). In
      one patient, the additional region of the short arm of chromosome 3 was 3pter
      p26.1 from maternal origin, measuring approximately 9 Mb in size. The second
      patient had an extra 14q32.1-qter of maternal origin, measuring approximately 14
      Mb in size. These are one of the shortest partial distal trisomy among reported
      cases. Taken together, two patients with partial trisomy 21 lack all of DSCR on
      21q22, and their distinct clinical features are likely caused by the genes
      located at 21pter-q22.1 and the distal part of chromosome 3p or 14q.

PMID- 16411204
TI  - Human and pig SRY 5' flanking sequences can direct reporter transgene expression
      to the genital ridge and to migrating neural crest cells.
AB  - Mechanisms for sex determination vary greatly between animal groups, and include
      chromosome dosage and haploid-diploid mechanisms as seen in insects, temperature
      and environmental cues as seen in fish and reptiles, and gene-based mechanisms as
      seen in birds and mammals. In eutherian mammals, sex determination is genetic,
      and SRY is the Y chromosome located gene representing the dominant testes
      determining factor. How SRY took over this function from ancestral mechanisms is
      not known, nor is it known what those ancestral mechanisms were. What is known is
      that SRY is haploid and thus poorly protected from mutations, and consequently is
      poorly conserved between mammalian species. To functionally compare SRY promoter
      sequences, we have generated transgenic mice with fluorescent reporter genes
      under the control of various lengths of human and pig SRY 5' flanking sequences.
      Human SRY 5' flanking sequences (5 Kb) supported reporter transgene expression
      within the genital ridge of male embryos at the time of sex determination and
      also supported expression within migrating truncal neural crest cells of both
      male and female embryos. The 4.6 Kb of pig SRY 5' flanking sequences supported
      reporter transgene expression within the male genital ridge but not within the
      neural crest; however, 2.6 Kb and 1.6 Kb of pig SRY 5' flanking sequences
      retained male genital ridge expression and now supported extensive expression
      within cells of the neural crest in embryos of both sexes. When 2 Kb of mouse SRY
      5' flanking sequences (-3 to -1 Kb) were placed in front of the 1.6 Kb of pig SRY
      5' flanking sequences and this transgene was introduced into mice, reporter
      transgene expression within the male genital ridge was retained but neural crest
      expression was lost. These observations suggest that SRY 5' flanking sequences
      from at least two mammalian species contain elements that can support transgene
      expression within cells of the migrating neural crest and that additional SRY 5'
      flanking sequences can extinguish this expression.

PMID- 16411205
TI  - Dose-dependent separation of the hypertrophic and myotoxic effects of the beta(2)
      adrenergic receptor agonist clenbuterol in rat striated muscles.
AB  - Muscle growth in response to large doses (milligrams per kilogram) of beta(2)
      adrenergic receptor agonists has been reported consistently. However, such doses
      may also induce myocyte death in the heart and skeletal muscles and hence may not
      be safe doses for humans. We report the hypertrophic and myotoxic effects of
      different doses of clenbuterol. Rats were infused with clenbuterol (range, 1
      microg to 1 mg.kg(-1)) for 14 days. Muscle protein content, myofiber cross
      sectional area, and myocyte death were then investigated. Infusions of >or=10
      microg.kg(-1).d(-1) of clenbuterol significantly (P<0.05) increased the protein
      content of the heart (12%-15%), soleus (12%), plantaris (18%-29%), and tibialis
      anterior (11%-22%) muscles, with concomitant myofiber hypertrophy. Larger doses
      (100 microg or 1 mg) induced significant (P<0.05) myocyte death in the soleus
      (peak 0.2+/-0.1% apoptosis), diaphragm (peak 0.15+/-0.1% apoptosis), and
      plantaris (peak 0.3+/-0.05% necrosis), and significantly increased the area
      fraction of collagen in the myocardium. These data show that the low dose of 10
      microg.kg(-1).d(-1) can be used in rats to investigate the anabolic effects of
      clenbuterol in the absence of myocyte death.

PMID- 16411206
TI  - Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing
      tumors.
AB  - BACKGROUND: The prognosis of Ewing tumor (ET) patients has significantly improved
      to cure rates approximating 70%. The prognosis in relapse, however, is poor.
      Promising response rates have recently been reported for the combination of
      topotecan (TOPO) and cyclophosphamide (CYC) encouraging wider application of this
      combination in patients with relapsed ETs. This report summarizes the experience
      of patients treated with TOPO/CYC for recurrent or refractory disease within the
      German ET trials. PROCEDURE: Fifty-four patients aged 3.2-49.5 (median: 17.4)
      years received TOPO (0.75 mg/m2/day, days 1-5) and CYC (250 mg/m2/day, days 1-5)
      following first (40) or second (6) relapse or progression under first-line
      therapy (8). RESULTS: A median of 3 (range: 1-11) TOPO/CYC courses were given.
      Sixteen patients (32.6%) showed partial response (PR), 13/49 (26.5%) had stable
      disease (SD), 14/49 (28.6%) progressed, 2/49 (4.1%) showed a mixed response (MR).
      In 4 patients response was not documented, 5/54 patients with complete initial
      resection at the diagnosis of relapse were excluded from the response analysis.
      At completion of relapse therapy, 24/54 patients had entered complete (19) or
      partial (5) remission, 2 had SD, 26 showed progression, information was
      unavailable in 2 patients. Of the 19 relapse patients achieving complete response
      (CR), 10 maintained remission (52.6%). At the time of evaluation, after a median
      follow-up for survivors of 23.1 (range: 7.8-59.8) months from the event prompting
      TOPO/CYC treatment, 14/54 patients (25.9%) were in continuous complete (13) or
      partial (1) remission. Overall survival (OAS) after 1 year was 0.61 (95%-CI 0.47
      0.74). CONCLUSION: TOPO/CYC is active in relapsed ETs and warrants further
      evaluation.

PMID- 16411207
TI  - Weighing the risks of G-CSF administration, leukopheresis, and standard marrow
      harvest: ethical and safety considerations for normal pediatric hematopoietic
      cell donors.
AB  - BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is used for collection
      of hematopoietic cells in most adult and a smaller but significant percentage of
      pediatric normal donor harvests. Short and long-term risks of G-CSF
      administration and leukopheresis are not well understood in the pediatric
      population. PROCEDURE: Literature review including observations from the IBMTR,
      NMDP, EBMT, German Donor Registry, and the authors' work. RESULTS: G-CSF causes
      temporary discomfort in a minority of younger donors. Rare serious side effects
      of G-CSF have yet to be reported in children. To date, an increase in
      hematological malignancies after short-term G-CSF use has not been detected in
      adult donors and no cases have been reported in children. Reported complications
      of leukopheresis in children are rare and minor, but donors <20 kg may be exposed
      to allogeneic blood products. Pediatric aged donors vary widely in their ability
      to assent or consent to the risks of a donation procedure. There are key
      regulations and ethical imperitives, which must be addressed in deciding which
      donation procedures are appropriate for minors. CONCLUSIONS: While short term
      administration of G-CSF and leukopheresis appear to be safe and effective
      procedures when used to assist in collection of a hematopoietic cell graft from a
      normal pediatric donor, institutions adding or substituting one or both of these
      procedures for standard marrow donation must decide whether the donor should be
      considered a research subject, and if so, whether the new procedures are a minor
      increase over minimal risk. Because these procedures are being performed on and
      off study at many pediatric centers, a comprehensive study addressing donor
      safety could help clarify risks of rare adverse events.

PMID- 16411208
TI  - Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer
      patients.
AB  - BACKGROUND: The hormone ghrelin and the adipocytokines leptin and adiponectin
      participate in body weight regulation. In response to weight loss, ghrelin and
      adiponectin levels increase and leptin decreases. Cancer cachexia is a complex
      metabolic state, characterized by loss of muscle mass and adipose tissue together
      with anorexia. The authors hypothesized that responses of these hormones may be
      attenuated in cancer cachexia. METHODS: Fasting plasma ghrelin, adiponectin, and
      leptin levels, as well as weight loss, were determined in 40 cancer patients: 18
      of them suffered from cancer-induced cachexia, and 22 served as a comparison
      group. Hormone levels were measured before administration of cancer therapy.
      RESULTS: A similar distribution of age, gender, and diagnosis was observed in
      both study groups, but the cachectic patients had higher rates of metastatic
      disease and lower albumin levels. No significant correlation was observed between
      plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher
      among cachectic compared with noncachectic patients. Notably, the association
      between ghrelin levels and weight loss was only modest, and in a third of the
      cachectic patients, ghrelin levels were equal to or lower than those in the
      noncachectic group. Plasma leptin levels showed gender-dependent associations,
      and significantly lower levels were found among cachectic women but not among
      cachectic men. CONCLUSIONS: Results suggested a gender-dependent attenuation of
      expected physiologic responses to weight loss among cancer cachexia patients.
      Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in
      the pathogenesis of cancer cachexia syndrome.

PMID- 16411209
TI  - Pediatric primary leptomeningeal lymphoma treated without cranial radiotherapy.
AB  - We report a case of primary leptomenigeal lymphoma (PLML) in an 11-year-old boy
      presenting with headache, vomiting, and diplopia. The patient was treated on an
      advanced non-Hodgkin lymphoma protocol with systemic/intrathecal chemotherapy
      without cranial radiotherapy. He remains in complete remission 33 months after
      treatment.

PMID- 16411210
TI  - Optic pathway gliomas.
AB  - Optic pathway gliomas represent approximately 5% of all pediatric intracranial
      tumors. While these tumors are most frequently low grade astrocytomas, they
      follow a highly variable clinical course, and accordingly, there is much debate
      regarding their optimal management. Their propensity to occur in very young
      children and infants further complicates selection of therapy. Historically,
      surgery and radiotherapy have played a primary role in management, however, in
      the last 15 years, chemotherapy has evolved into the first-line treatment of
      choice. Nonetheless, chemotherapy frequently fails, but serves to delay
      implementation of radiotherapy or surgery until the child has progressed
      neuropsychologically. An overall favorable prognosis for this tumor emphasizes
      the need for careful selection of therapy. Herein, we review the major features
      of optic pathway glioma, including epidemiology, pathology, therapeutic
      interventions, outcome, and treatment sequelae.

PMID- 16411211
TI  - Langerhans cell histiocytosis: too many cytokines, not enough gene regulation?

PMID- 16411212
TI  - Evaluation of persistent pulmonary infiltrates in pediatric oncology patients.
AB  - PURPOSE: To evaluate the role of bronchoalveolar lavage (BAL), computed
      tomography-guided biopsy (CTB), and open lung biopsy (OLB) in the management of
      persistent pulmonary infiltrates in pediatric oncology patients. METHODS:
      Retrospective review of clinical records of pediatric oncology patients who
      underwent BAL, CTB, and OLB over a 7-year period. Data was compared across the
      three procedures using chi-square analysis. Logistic regression was used to
      adjust potential confounding variables for diagnostic yield. RESULTS: There were
      113 consecutive patients who underwent 140 separate procedures during their
      hospitalization. Thirty (26%) patients had a previous BMT. BALs were more likely
      to occur as the first line of investigation (98% vs. 47%, 45%; P < 0.01) and in
      patients with diffuse infiltrates (64% vs. 6%, 26%; P < 0.01) when compared to
      CTB and OLB, respectively. OLBs were performed less frequently in neutropenic
      patients (26% vs. 53%, 54%; P < 0.05), more often led to change in management
      directly because of procedure (61% vs. 12%, 33%; P < 0.01), and had higher
      diagnostic yield (61% vs. 24%, 36%; P < 0.01) when compared to CTB and BAL,
      respectively. Diagnostic yield of OLB was significantly higher regardless of
      diffuse or focal nature of infiltrate. Major adverse events after a procedure
      were not significantly different across the three procedures. Logistic regression
      demonstrated that having an OLB was independently associated with identifying the
      cause of pulmonary infiltrate. CONCLUSION: OLB appears to be safe, has the best
      diagnostic yield, and leads to change in management more often than CTB or BAL in
      pediatric oncology patients with persistent pulmonary infiltrates.

PMID- 16411213
TI  - A father and son with mental retardation, a characteristic face, inv(12), and
      insertion trisomy 12p12.3-p11.2.
AB  - A male patient with mental retardation (MR) and mild facial features was shown by
      high-resolution G-banding to have pericentric inversion of chromosome 12 with an
      unknown segment inserted into the long arm of the inverted chromosome
      [46,XY,inv(12)(pter-->p11.2::q14.1-->p11.2::?::q14.1-->qter)]. Both the inverted
      chromosome 12 and clinical manifestations were transmitted to his son. Karyotypes
      of the propositus' parents were normal. Studies with fluorescence in situ
      hybridization (FISH) in both the propositus and his son revealed that the extra
      segment was derived from 12p. Further FISH mapping and the genome-wide copy
      number detection by GeneChip Mapping 100K Array showed that an 11-Mb segment of
      12p between two BAC clones, RP11-22H10 and RP11-977P2, was inserted at one of the
      reunion points in the long arm of the inv(12) chromosome. Analysis of parent
      child transmissions of duplicated alleles using microsatellite markers defined
      the maternal origin of the chromosomal anomaly in the propositus and suggested a
      mechanism of its formation through a sister-chromatid rearrangement (SCR), that
      is, mismatched pairing and unequal crossover between sister chromatids as well as
      three break rearrangements including a U type rearrangement. Karyotypes of the
      propositus and his son were thus inv(12)(pter-->p11.22::q14.1-->p12.3::q14.1-
      >qter). This is the first report of "pure" proximal 12p-trisomy including p12.3
      p11.22 region.

PMID- 16411214
TI  - Pathologic findings from the Breast Cancer Surveillance Consortium: population
      based outcomes in women undergoing biopsy after screening mammography.
AB  - BACKGROUND: To the authors' knowledge, a comprehensive analysis of pathology
      outcomes after screening mammography, as it is practiced clinically in the U.S.
      general population, has not been performed. METHODS: Breast Cancer Surveillance
      Consortium data from 1996-2001 were used to identify pathology specimens that
      were obtained within 1 year of screening mammograms performed on 786,846 women
      ages 40-89 years. The pathology results were classified as invasive carcinoma,
      ductal carcinoma in situ (DCIS), or benign. The associations between overall
      pathology outcomes and invasive tumor size and lymph node status were analyzed by
      age and mammography assessment category. RESULTS: The rates of both recommending
      and performing a biopsy varied little with age. The 1,664,032 screening
      mammograms were followed by 26,748 known biopsies (1.6%) and 8815 diagnoses of
      breast carcinoma (0.53%). Overall, 81% of carcinomas were invasive, and 78% of
      those were pathologically lymph node-negative tumors, in contrast to the 66%
      prevalence observed in the Surveillance, Epidemiology, and End Results (SEER)
      data during the same period. Most invasive tumors measured between 0 mm and 10 mm
      (35%) or between 11 mm and 20 mm (36%) in greatest dimension, and 92% and 78%
      were lymph node-negative tumors, respectively: Biopsy results that were
      classified as malignant increased with age (P < 0.0001) and were most likely to
      follow Breast Imaging, Reporting, and Diagnosis System Category 5 and 4
      assessments, respectively. Ductal hyperplasia (19.6%), fibroadenoma (18.5%), and
      other benign findings (56.1%) were the most common benign diagnoses. CONCLUSIONS:
      Pathologically negative lymph nodes were more prevalent in this mammographically
      screened population than in the overall SEER population. The prevalence of
      invasive carcinoma, DCIS, and benign findings presented herein establish a range
      of expected biopsy outcomes for women after screening mammography in the general
      U.S. population.

PMID- 16411215
TI  - A novel mutation in the gene encoding TIMM8a, a component of the mitochondrial
      protein translocase complexes, in a Spanish familial case of deafness-dystonia
      (Mohr-Tranebjaerg) syndrome.

PMID- 16411216
TI  - Twenty-five years of follow-up in patients with operable breast carcinoma:
      correlation between clinicopathologic factors and the risk of death in each 5
      year period.
AB  - BACKGROUND: Some investigators have suggested a decreased prognostic value for
      conventional prognostic factors over time in patients with breast carcinoma. The
      objective of this study was to assess the effect of prognostic factors on the
      risk of death in patients with breast carcinoma over a long follow-up. METHODS:
      The authors assessed clinicopathologic prognostic factors in patients with early
      stage breast carcinoma over a follow-up > 25 years and analyzed the variation of
      their effect on death in consecutive 5-year follow-up intervals. The study
      included 2410 women who primarily underwent complete surgical resection. Time
      dependent variables were analyzed by using different multivariate models.
      RESULTS: Four factors were related strongly to the risk of death in the first 5
      years: tumor size, histologic grade, the number of involved axillary lymph nodes,
      and age at diagnosis. After 10-15 years of follow-up, only age at diagnosis was
      related to the risk of death. The effect of powerful prognostic factors, except
      age at diagnosis, on the risk of death was time limited, and no effects or very
      small effects were detectable after 10 years of follow-up. CONCLUSIONS:
      Conventional and widely accepted prognostic factors may explain a significant
      portion of early deaths among patients with early-stage breast carcinoma, but
      they were of limited value to explain late mortality, that also may be influenced
      by late events, such as new primary malignancies and treatment complications.
      Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16411218
TI  - Pure direct duplication (12)(q24.1-->q24.2) in a child with Marcus Gunn
      phenomenon and multiple congenital anomalies.
AB  - Partial trisomy of the region 12q24.1-->q24.2 is rare and usually associated with
      other rearrangements. We report on the clinical and cytogenetic findings in a
      girl with a pure de novo direct duplication dup(12)(q24.1-->q24.2). She had
      developmental and growth retardation, facial dysmorphism with upslanting
      palpebral fissures, wide downturned mouth, short neck, and Marcus Gunn
      phenomenon. She also had single transverse creases, hypoplasia of the corpus
      callosum, and cardiac malformations consisting of a bicuspid aortic valve,
      multiple ventricular septal defects, and kinking of the aorta. The size of the
      duplication was characterized by molecular cytogenetics and comparative genomic
      hybridization (CGH) to be 11.5 Mb in size and extended from the BAC probe RP11
      256L11 loci (108.2 Mb) +/- 1 Mb to the BAC probe RP11-665J20 loci (119.7 Mb) +/-
      1 Mb. No such pure 12q24 duplication was detected out of the 23 patients reported
      in the literature with duplications in 12q region. Comparison with these reported
      12q trisomies suggests the duplication dup(12)(q24.1-->q24.2) is associated with
      a recognizable phenotype consisting of characteristic facial dysmorphism, growth
      retardation, and cardiac malformation.

PMID- 16411217
TI  - Risk evaluation of carriers with chromosome reciprocal translocation
      t(7;13)(q34;q13) and concomitant meiotic segregation analyzed by FISH on
      ejaculated spermatozoa.
AB  - We performed the segregation analysis of a relatively large pedigree of
      t(7;13)(q34;q13) carriers together with the sperm karyotype analysis of the one
      carrier using a tri-color fluorescence in situ hybridization (FISH) method. The
      risk assessments for unfavorable pregnancy outcomes in a series of 36 pregnancies
      in eight reciprocal chromosome translocation (RCT) couples of carriers were
      estimated directly from a pedigree after ascertainment correction. The individual
      probability rate for unbalanced child was predicted according to Stengel
      Rutkowski and co-workers. The unbalanced karyotypes in the form of monosomy 7q34-
      >qter and trisomy 13q13-->qter were detected among stillborn/early death newborns
      with holoprosencephaly (HPE), cyclopia and other malformations. Based on clinical
      description of unkaryotyped stillbirth progeny, it can be assumed that the
      phenotype distinctions were connected with the unbalanced karyotype from 2:2
      segregation (monosomy 7q with trisomy 13q) and 3:1 segregation as interchange
      trisomy 13 (Patau syndrome). Probability rates for miscarriages, stillbirth/early
      death were 12.9 +/- 6% (4/31) and 29 +/- 8.2% (9/31), respectively. The results
      of the meiotic segregation pattern indicated the rate of unbalanced spermatozoa
      for about 60%, with the unusual high rate (29.4%) of 3:1 segregant (i.e., 13.4%
      of the tertiary segregation and 16% of the interchange segregation). Adjacent-1
      segregation followed with 23.5% and adjacent-2 followed with 7.2% of analyzed
      spermatozoa. The high rate of unbalanced gametes in comparison to the number of
      stillborn/early death and miscarriages detected in pedigree suggests a strong
      selection against unbalanced chromosomal constitutions during fetal development.
      It corresponds to a very small probability rate (about 0.3%) of viable unbalanced
      progeny from 3:1 meiotic segregation predicted for maternal carriers. This
      knowledge can be used in genetic counseling of families with similar RCT
      ascertained in a different way.

PMID- 16411220
TI  - High heritability of fingertip arch patterns in twin-pairs.
AB  - The presence of an arch pattern on at least one fingertip has previously been
      suggested as an autosomal dominant trait with reduced penetrance, although the
      examination of pedigrees with this trait segregating is also consistent with
      major gene or multifactorial inheritance. We utilized fingerprints in 2,484 twin
      pairs to estimate heritability for the presence of at least one fingertip arch
      pattern. The frequency of arches in the entire sample was 4.3% (2,175/50,850),
      5.5% in females and 3.2% in males. There were 267 twin-pairs concordant for the
      presence of an arch on any finger. Structural equation modeling was performed to
      contingency table data for five groups (MZ male, MZ female, DZ male, DZ female,
      and unlike-sexed DZ). The best fitting model, which allowed for the prevalence of
      arches to differ between males and females, had a heritability of 91%. There was
      some evidence for small dominant genetic effects in females and shared
      environmental effects in males, although both were not significant. With such
      high heritability, the search for specific genes influencing the occurrence of
      fingertip arch patterns is justified.

PMID- 16411219
TI  - Severe complications in a child with achondroplasia and two FGFR3 mutations on
      the same allele.
AB  - We describe a unique case of achondroplasia with associated complications,
      including severe respiratory problems. Molecular analysis of the fibroblast
      growth factor receptor type 3 (FGFR3) gene in this patient showed the common
      p.G380R mutation and a second novel p.L377R mutation. An allele-specific PCR
      demonstrated that these mutations were on the same allele (cis). Both mutations
      were not present in the parents and appear to have occurred de novo. To our
      knowledge, this is the first report in the literature on an achondroplasia
      patient with two FGFR3 mutations on the same allele.

PMID- 16411221
TI  - Second and third malignant solid tumor in a girl with ovarian Sertoli-Leydig
      tumor.
AB  - We report a Sertoli-Leydig cell (SLC) tumor of the right ovary in a 10-year-old
      girl, which was dealt with surgical removal. Three months after resection, she
      presented with a new episode of acute abdomen because of an abdominal mass, which
      histologically was compatible with an undifferentiated embryonal
      rhabdomyosarcoma. Chemotherapy, according to SIOP-??? 89 protocol, was
      administered additionally to radiotherapy (3,960 cGy). Three years after
      completing treatment, the patient developed a painful swelling at her left upper
      arm. The diagnosis was Ewing sarcoma of the humerus, which was confirmed by
      identification of the typical 11; 22 translocation on cytogenetic and molecular
      analysis of the tumor tissue. The patient died 14 months from Ewing diagnosis due
      to progressive disease.

PMID- 16411222
TI  - Prostate cancer screening in high-risk men: African American Hereditary Prostate
      Cancer Study Network.
AB  - BACKGROUND: There are scant data available on prostate cancer screening among
      high-risk African American men with positive family histories. It is important to
      determine whether or not their screening rates differ from those in the general
      population. METHODS: This study computed rates of previous digital rectal
      examination (DRE) and prostate-specific antigen (PSA) screening for prostate
      cancer in cancer-free (unaffected) relatives age 40-69 years from African
      American families that had four or more men with prostate cancer. The rates for
      these 134 high-risk African American men from the African American Hereditary
      Prostate Cancer Study (AAHPC) were compared with nationwide estimates obtained
      from participants in the 1998 and 2000 National Health Interview Survey (NHIS),
      for which the numbers of demographically comparable subjects were 5583 (4900
      Caucasians, plus 683 African Americans) and 3359 (2948 Caucasians, 411 African
      Americans), respectively. RESULTS: Men in the AAHPC cohort (with a strong
      positive family history) had significantly less screening than both African
      Americans and Caucasians in the NHIS cohorts. Only about one-third (35%) of the
      men in the AAHPC unaffected cohort had ever had a DRE, and only about 45% of them
      had ever received a PSA test. These rates were much lower than those obtained for
      African American men in the NHIS: 45% for DRE and 65% for PSA. These
      discrepancies increased with age. CONCLUSIONS: Older African American men with
      positive family histories report surprisingly low rates of DRE and PSA screening
      compared with their counterparts in the NHIS surveys. At-risk men need to be
      informed of the benefits and limitations of prostate cancer screening and
      actively involved in decision-making for or against prostate cancer screening.

PMID- 16411223
TI  - Randomized Phase II study of two opposite administration sequences of irinotecan
      and cisplatin in patients with advanced nonsmall cell lung carcinoma.
AB  - BACKGROUND: Combined chemotherapy with irinotecan and cisplatin (IP) is active in
      patients with nonsmall cell lung carcinoma (NSCLC). However, the optimal
      administration schedule needs to be defined to maximize its synergic effect. The
      authors evaluated the efficacy, toxicity, and pharmacokinetics (PK) of IP
      chemotherapy given on two administration sequences in chemotherapy-naive patients
      with NSCLC. METHODS: Eighty eligible patients were assigned randomly to receive 1
      of 2 irinotecan and cisplatin administration sequences on Day 1: irinotecan
      followed by cisplatin (I-P) (n = 39 patients) or cisplatin followed by irinotecan
      (P-I) (n = 41 patients). Treatment was comprised of irinotecan at a dose of 80
      mg/m(2) intravenously on Days 1 and 8 and cisplatin at a dose of 60 mg/m(2)
      intravenously on Day 1 of a 21-day cycle for a maximum of 6 cycles. For PK
      analysis, serial plasma samples were obtained on Day 1 of the first cycle.
      RESULTS: In total, 77 patients were assessable for efficacy. The overall response
      rate was 47%, and there was a trend in favor of P-I (54%) compared with I-P
      (39%). In multivariate logistic regression analysis, the P-I sequence and female
      gender were found to be significant predictors of a better response (P = 0.047
      and P = 0.011, respectively). Overall toxicity profiles and PK parameters were
      similar in both arms. CONCLUSIONS: IP chemotherapy showed promising activity with
      a favorable 1-year survival rate. For future clinical use, the authors recommend
      administering cisplatin first and then irinotecan, because that sequence was
      associated with a higher response rate.

PMID- 16411225
TI  - Assessment of the role of sentinel lymph node biopsy for primary cutaneous
      desmoplastic melanoma.
AB  - BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in the treatment of
      desmoplastic melanoma (DM) remains undefined. The purpose of this study was to
      evaluate the use of SLNB for DM. METHODS: In all, 1850 patients with cutaneous
      melanoma underwent wide local excision and SLNB. Patients with DM were identified
      and stratified as 'pure' DM or 'mixed' DM (i.e., DM associated with at least one
      other common histologic subtype). RESULTS: Of the 1850 patients, 65 (3.5%) had
      DM. Of these, 46 (70.8%) had pure DM and 19 (29.2%) had mixed DM. Patients with
      pure DM had a median tumor thickness of 3.5 mm and 6.5% were ulcerated. Compared
      with patients with pure DM, patients with either mixed DM or non-DM (n = 1785)
      had thinner primary tumors (median, 1.7 mm and 1.5 mm, respectively, each P <
      0.001 vs. pure DM) that were more likely to be ulcerated (27.7% and 21.3%,
      respectively, each P < 0.05 vs. pure DM). Although the incidence of a positive
      SLN was similar in patients with mixed DM (15.8%) and non-DM (17.5%), patients
      with pure DM were less likely to have a positive SLN (2.2%) (each P < 0.01 vs.
      non-DM and mixed DM). At a median follow-up of 2.9 years, no patient with pure DM
      had recurred. CONCLUSIONS: Despite having thicker primary tumors, patients with
      pure DM have a lower incidence of positive SLNs compared with patients with non
      DM. Whereas the treatment approach for patients with mixed DM should be similar
      to that of other melanoma patients, patients with pure DM are unlikely to have
      metastatic disease in regional lymph nodes and SLNB may not be warranted.

PMID- 16411224
TI  - Role of exposure to radon and silicosis on the cell type of lung carcinoma in
      German uranium miners.
AB  - BACKGROUND: In East Germany, uranium mining was undertaken on a large scale from
      1946 to 1990. Poor working conditions led to a high level of exposure to ionizing
      radiation and quartz dust. This analysis evaluates the histopathology of lung
      carcinoma in uranium miners in relation to radon exposure and silicosis. METHODS:
      A database developed for autopsy cases ascertained in a pathological tissue
      repository of German uranium miners was used to estimate odds ratios for
      developing lung carcinoma by major cell type with regard to radon exposure and
      silicosis. Silicosis information was extracted from autopsy protocols. Working
      level months (WLM) were calculated with a job-exposure matrix to assess lifetime
      radon exposure. Risk estimates were based on 3414 male miners who died from small
      cell lung carcinoma (SCLC, n = 1446), squamous cell carcinoma (SqCC, n = 1006),
      or adenocarcinoma (AC, n = 962) between 1957 and 1990. RESULTS: SCLC and SqCC
      seem more likely to be associated with high radon exposure than AC. Mean
      cumulative radon exposure was 868 (SD 631) WLM in SCLC, 871 (SD 652) WLM in SqCC,
      and 743 (SD 598) WLM in AC. Silicosis prevalence was 26% in SCLC, 38% in SqCC,
      and 30% in AC. In silicotics, AC and SqCC had a relatively higher frequency at
      the expense of SCLC. SCLC occurred earlier than AC and SqCC. CONCLUSION: High
      radon exposure was associated with a higher relative frequency of SCLC and SqCC
      than AC. Silicosis tended to increase the appearance of SqCC and AC.

PMID- 16411226
TI  - Comparison of the accuracy of magnetic resonance imaging and positron emission
      tomography/computed tomography in the presurgical detection of lymph node
      metastases in patients with uterine cervical carcinoma: a prospective study.
AB  - BACKGROUND: The objective of the current study was to determine the accuracy of
      magnetic resonance imaging (MRI) and positron emission tomography/computed
      tomography (PET/CT) for detecting lymph node metastases in patients with uterine
      cervical carcinoma compared with thin-section histopathologic results from
      systemic lymphadenectomy. METHODS: Twenty-two patients with International
      Federation of Obstetrics and Gynecology (FIGO) Stage IB-IVA cervical carcinoma
      who underwent both MRI and PET/CT before lymphadenectomy were included in this
      study. Lymphadenectomy involved removing all visible lymph nodes in the surgical
      fields. To enable region-specific comparisons, paraaortic and pelvic lymph nodes
      were divided into seven regions: the paraaortic area, both common iliac areas,
      both external iliac areas, and both internal iliac/obturator areas.
      Histopathologic evaluation of lymph nodes was the diagnostic standard. Chi-square
      analysis was used to compare the accuracy of MRI and PET/CT for the detection of
      metastatic lymph nodes. A P value < or = 0.05 was considered statistically
      significant. RESULTS: With MRI, the sensitivity, specificity, and accuracy rates
      for detecting metastatic lymph nodes in each lymph node group were 30.3% (10 of
      33 lymph node groups), 92.6% (112 of 121 lymph node groups), and 72.7% (122 of
      154 lymph node groups), respectively; with PET/CT, those rates were 57.6% (19 of
      33 lymph node groups), 92.6% (112 of 121 lymph node groups), and 85.1% (131 of
      154 lymph node groups), respectively. Statistical analysis showed that PET/CT was
      more sensitive than MRI (P = 0.026) but that there were no statistical
      differences noted with regard to specificity (P = 1.000) or accuracy (P = 0.180).
      Power analysis demonstrated that a sample size of 685 lymph node groups (98
      patients) would be necessary to demonstrate that PET/CT was more accurate than
      MRI (alpha = 0.05; beta = 0.80). CONCLUSIONS: PET/CT was more sensitive than MRI
      for detecting lymph node metastases in patients with uterine cervical carcinoma.

PMID- 16411227
TI  - Are venous thromboembolic events associated with subsequent breast and colorectal
      carcinoma diagnoses in the elderly? A case-control study of Medicare
      beneficiaries.
AB  - BACKGROUND: Multiple epidemiologic studies have reported associations between
      venous thromboembolic events and subsequent cancer diagnoses, but the published
      results have not suggested clear cancer screening approaches. METHODS: Using data
      from the National Cancer Institute's Surveillance, Epidemiology, and End Results
      Medicare Program, the authors identified patients who were diagnosed with breast
      and colorectal carcinoma (n = 7166 patients) and compared them with a noncancer
      control group (n = 126,668 patients) according to their history of
      hospitalization for deep vein thrombosis (DVT) or pulmonary embolism (PE) in
      Medicare claims files over the previous 24 months. Using logistic regression
      analysis, the authors calculated the odds of receiving a diagnosis of breast
      carcinoma or colorectal carcinoma in the 24 months after admission for DVT or PE.
      RESULTS: Patients who were hospitalized for DVT or PE had nearly 3.0 times the
      odds of being diagnosed with colorectal carcinoma (odds ratio [OR], 2.83; 95%
      confidence interval [95% CI], 1.92-4.17) and > 1.5 times the odds of being
      diagnosed with breast carcinoma (OR, 1.78; 95% CI, 1.05-3.02) in the subsequent
      24 months. CONCLUSIONS: Because hospitalization for DVT or PE is associated with
      an increased risk of a breast or colorectal carcinoma diagnosis in the subsequent
      2 years, physicians should be vigilant in assessing the cancer screening status
      of patients with new DVT and/or PE to be certain that they are up to date with
      recommended breast and colorectal screening guidelines.

PMID- 16411228
TI  - Smaller white-matter volumes are associated with larger deficits in attention and
      learning among long-term survivors of acute lymphoblastic leukemia.
AB  - BACKGROUND: The primary objective of this study was to test the hypothesis that
      survivors of childhood acute lymphoblastic leukemia (ALL) have deficits in
      neurocognitive performance, and smaller white-matter volumes are associated with
      these deficits. METHODS: The patients studied included 112 ALL survivors (84
      patients who had received chemotherapy only, 28 patients who had received
      chemotherapy and irradiation; 63 males, 49 females; mean age +/- standard
      deviation, 4.1 yrs +/- 2.6 yrs at diagnosis; mean +/- standard deviation yrs
      since diagnosis, 6.0 +/- 3.5 yrs), and 33 healthy siblings who participated as a
      control group. Neurocognitive tests of attention, intelligence, and academic
      achievement were performed; and magnetic resonance images were obtained and
      subsequently were segmented to yield tissue volume measurements. Comparisons of
      neurocognitive measures and tissue volumes between groups were performed, and the
      correlations between volumes and neurocognitive performance measures were
      assessed. RESULTS: Most performance measures demonstrated statistically
      significant differences from the normative test scores, but only attention
      measures exceeded 1.0 standard deviation from normal. Patients who had received
      chemotherapy alone had significantly larger volumes of white matter than patients
      who had received treatment that also included cranial irradiation, but their
      volumes remained significantly smaller than the volumes in the control group.
      Smaller white-matter volumes were associated significantly with larger deficits
      in attention, intelligence, and academic achievement. CONCLUSIONS: Survivors of
      childhood ALL had significant deficits in attention and smaller white-matter
      volumes that were associated directly with impaired neurocognitive performance.
      Cranial irradiation exacerbated these deficits.

PMID- 16411229
TI  - GABA(B) receptors inhibit backpropagating dendritic spikes in hippocampal CA1
      pyramidal cells in vivo.
AB  - Spike backpropagation has been proposed to enhance dendritic depolarization and
      synaptic plasticity. However, relatively little is known about the inhibitory
      control of spike backpropagation in vivo. In this study, the backpropagation of
      the antidromic spike into the dendrites of CA1 pyramidal cells was studied by
      extracellular recording in urethane-anesthetized rats. The population antidromic
      spike (pAS) in CA1 following stimulation of the alveus was recorded
      simultaneously with a 16-channel silicon probe and analyzed as current source
      density (CSD). The pAS current sink was shown to sequentially invade the soma and
      then the apical and basal dendrites. When the pAS was preceded <400 ms by a
      conditioning orthodromic CA3 stimulus, the apical and basal dendritic spike sinks
      were reduced and delayed. Dendritic spike suppression was large after a high
      intensity CA3 conditioning stimulus that evoked a population spike, small after a
      low-intensity CA3 conditioning stimulus, and weak after conditioning by another
      pAS. The late (150-400 ms latency) inhibition of the backpropagating pAS at the
      apical and basal dendrites was partially relieved by a GABA(B) receptor
      antagonist, CGP35348 or CGP56999A, given intracerebroventricularly (icv).
      CGP35348 icv also decreased the latency of the antidromic spike sinks at all
      depths. A compartment cable model of a CA1 pyramidal cell with excitable
      dendrites, combined with a model of extracellular potential generation, confirms
      that GABA(B) receptor activation delays a backpropagating spike and blocks distal
      dendritic spikes. GABA(B) receptor-mediated conductance increase and
      hyperpolarization, amplified by removing dendritic I(A) inactivation, contribute
      to conditioned dendritic spike suppression. In addition, the model shows that
      slow Na(+) channel inactivation also participates in conditioned spike
      suppression, which may partly explain the small dendritic spike suppression after
      conditioning with a weak orthodromic stimulus or another antidromic spike. Thus,
      both theory and experiment confirm an important role of the GABA(B) receptors in
      controlling dendritic spike backpropagation.

PMID- 16411230
TI  - Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for
      addiction and stem cell biology.
AB  - Once thought to produce global, nonspecific brain injury, drugs of abuse are now
      known to produce selective neuro-adaptations in particular brain regions. These
      neuro-adaptations are being closely examined for clues to the development,
      maintenance, and treatment of addiction. The hippocampus is an area of particular
      interest, as it is central to many aspects of the addictive process, including
      relapse to drug taking. A recently appreciated hippocampal neuro-adaptation
      produced by drugs as diverse as opiates and psychostimulants is decreased
      neurogenesis in the sub-granular zone (SGZ). While the role of adult-generated
      neurons is not clear, their functional integration into hippocampal circuitry
      raises the possibility that decreased adult SGZ neurogenesis may alter
      hippocampal function in such a way as to maintain addictive behavior or
      contribute to relapse. Here, we review the impact of opiates and psychostimulants
      on the different stages of cell development in the adult brain, as well as the
      different stages of the addictive process. We discuss how examination of drug
      induced alterations of adult neurogenesis advances our understanding of the
      complex mechanisms by which opiates and psychostimulants affect brain function
      while also opening avenues for novel ways of assessing the functional role of
      adult-generated neurons. In addition, we highlight key discrepancies in the field
      and underscore the necessity to move "beyond BrdU"--beyond merely counting new
      hippocampal cells labeled with the S phase marker bromodeoxyuridine--so as to
      probe mechanistic questions about how drug-induced alterations in adult
      hippocampal neurogenesis occur and what the functional ramifications of
      alterations in neurogenesis are for addiction.

PMID- 16411231
TI  - Neurogenesis in the adult hippocampus.
AB  - The dentate gyrus (DG) contains one of the few neuronal populations in the
      mammalian brain that are generated throughout life. Research into the regulation
      and function of adult neurogenesis continues its rapid growth in popularity. With
      the researcher new to the field in mind, we review the processes that together
      constitute adult neurogenesis and some of the methods most commonly used for
      studying these processes. (c) 2006 Wiley-Liss, Inc.

PMID- 16411232
TI  - Functional maturation of adult-generated granule cells.
AB  - The excitability and connectivity of adult-generated granule cells dictate to
      what extent newborn neurons participate in the hippocampal network. These
      functional parameters evolve as newborn cells mature and interact with the
      existing circuit. The progression of granule cell maturation during neonatal
      development appears to be reiterated in the adult, but with some caveats. New
      approaches to identify and track newborn neurons are revealing the timing of this
      process, as well as its sensitivity to activity-dependent regulation.

PMID- 16411233
TI  - Restrictive dermatopathy: a lethal congenital dermatosis and review of
      literature.

PMID- 16411234
TI  - Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with
      osteomas and sebaceous cysts.
AB  - Gardner syndrome is characterized by the triad of colorectal adenomas, soft and
      hard tissue tumors. This disorder was regarded as a separate disease until the
      identification of the APC gene when it was recognized that mutations in the APC
      gene were the underlying cause of both Gardner syndrome and familial adenomatous
      polyposis (FAP). The present study aimed at examining whether a particular APC
      genotype could be delineated in FAP patients with benign extracolonic
      manifestations: sebaceous cysts and/or osteomas. A questionnaire was sent to all
      Danish FAP patients (N = 234) asking for occurrence of sebaceous cysts and
      palpable osteomas. Medical records later verified positive findings, when
      possible. The results for each patient were correlated to the position of his or
      her mutation in the APC gene. Positive participation compliance was 77% (N =
      180), and in 105 of these patients the pathogenic APC mutation was known.
      Palpable osteomas were reported in 17 of the patients in whom a pathogenic
      mutation had been identified. Osteomas were only identified in patients with
      mutations between codon 767 and 1513, a gene area also associated with congenital
      hypertrophy of the retinal-pigmented epithelium (CHRPE) and hepatoblastoma.
      Sebaceous cysts were reported in 51% of the patients, and their APC mutations
      were evenly distributed in the gene with no particular hotspot. Osteomas appeared
      most frequently in patients with sebaceous cysts, odds ratio 6.6, P < 0.001. The
      study provides molecular evidence that Gardner syndrome is a variant of FAP and
      essentially obsolete in clinical practice.

PMID- 16411235
TI  - Diagnosis and management of heterokaryotypic monochorionic twins.
AB  - The diagnosis, management, and outcome of six consecutive heterokaryotypic
      monochorionic twins were evaluated. All suspected cases, based on discordant
      ultrasound findings, underwent amniocentesis of both sacs. Two cases also had
      chorionic villous sampling (CVS). Dual amniocentesis was superior to CVS in
      diagnosing heterokaryotypic monochorionic twins. In four cases, the X-chromosome
      was involved and autosomal aneuploidy was noted in the others. In five cases, the
      anomalous twin was selectively reduced by cord coagulation. All pregnancies ended
      with a phenotypically normal liveborn and all children are developing normally at
      1-7 years of age.

PMID- 16411236
TI  - Effect of ethanol on folding of hen egg-white lysozyme under acidic condition.
AB  - The equilibrium and kinetics of folding of hen egg-white lysozyme were studied by
      means of CD spectroscopy in the presence of varying concentrations of ethanol
      under acidic condition. The equilibrium transition curves of guanidine
      hydrochloride-induced unfolding in 13 and 26% (v/v) ethanol have shown that the
      unfolding significantly deviates from a two-state mechanism. The kinetics of
      denaturant-induced refolding and unfolding of hen egg-white lysozyme were
      investigated by stopped-flow CD at three ethanol concentrations: 0, 13, and 26%
      (v/v). Immediately after dilution of the denaturant, the refolding curves showed
      a biphasic time course in the far-UV region, with a burst phase with a
      significant secondary structure and a slower observable phase. However, when
      monitored by the near-UV CD, the burst phase was not observed and all refolding
      kinetics were monophasic. To clarify the effect of nonnative secondary structure
      induced by the addition of ethanol on the folding/unfolding kinetics, the kinetic
      m values were estimated from the chevron plots obtained for the three ethanol
      concentrations. The data indicated that the folding/unfolding kinetics of hen
      lysozyme in the presence of varying concentrations of ethanol under acidic
      condition is explained by a model with both on-pathway and off-pathway
      intermediates of protein folding.

PMID- 16411238
TI  - De novo pericentric inversion of chromosome 5 in a girl with mental retardation
      and unilateral ear malformation.

PMID- 16411237
TI  - Behavioral management of a long-term survivor with tetrasomy 18p.
AB  - We report on a 41-year-old male with dysmorphic features, marked obesity,
      profound mental retardation, and aggressive behavior who was recently diagnosed
      with tetrasomy of the short arm of chromosome 18, [47, XY, i(18)(p10)]. His
      initial diagnosis, based upon chromosomal analysis at 6 years of age in 1969, was
      "trisomy F syndrome." Approximately 60 cases of tetrasomy 18p are reported in the
      literature, with little information regarding their long-term behavioral profiles
      or outcomes from therapy. We describe the behavioral management as well as the
      medical and genetic evaluation for this older patient with tetrasomy. With
      improved preventive care and intervention, patients with rare chromosomal
      abnormalities are living longer and, therefore, provide insight into the natural
      history of their disorders. Efforts need to be directed toward behavior
      management, social skills training, and augmentation of communication if the
      quality of life of these individuals is to continue to improve.

PMID- 16411239
TI  - X-ray structure of a domain-swapped dimer of Ser46-phosphorylated Crh from
      Bacillus subtilis.

PMID- 16411240
TI  - The 1.6-A resolution crystal structure of NovW: a 4-keto-6-deoxy sugar epimerase
      from the novobiocin biosynthetic gene cluster of Streptomyces spheroides.

PMID- 16411241
TI  - Inhibition of neurogenesis interferes with hippocampus-dependent memory function.
AB  - Rats treated with low dose irradiation, to inhibit adult hippocampal
      neurogenesis, and control rats were administered a non-matching-to-sample (NMTS)
      task, which measured conditional rule learning and memory for specific events,
      and a test of fear conditioning in which a discrete CS was paired with an
      aversive US in a complex environment. Irradiated rats were impaired on the NMTS
      task when the intervals between sample and test trials were relatively long, and
      in associating the shock-induced fear with contextual cues in the fear
      conditioning task. Irradiated rats were not impaired in learning the basic NMTS
      rule or in performing that task when the intervals between the sample and test
      trials were short. Nor were there group differences in conditioning the fear
      response to the CS in the fear conditioning task. The results, which extend the
      range of hippocampus-dependent tasks that can be said to be vulnerable to the
      effects of neurogenesis suppression, support the hypothesis that new hippocampal
      cells generated in adulthood participate in a broad range of hippocampal
      functions.

PMID- 16411242
TI  - Environmental enrichment and voluntary exercise massively increase neurogenesis
      in the adult hippocampus via dissociable pathways.
AB  - Environmental enrichment (EE) and voluntary exercise (VEx) have consistently been
      shown to increase adult hippocampal neurogenesis and improve spatial learning
      ability. Although it appears that these two manipulations are equivalent in this
      regard, evidence exists that EE and VEx affect different phases of the neurogenic
      process in distinct ways. We review the data suggesting that EE increases the
      likelihood of survival of new cells, whereas VEx increases the level of
      proliferation of progenitor cells. We then outline the factors that may mediate
      these relationships. Finally, we provide a model showing that VEx leads to the
      convergence of key somatic and cerebral factors in the dentate gyrus (DG) to
      induce cell proliferation. Although insufficient evidence exists to provide a
      similar model for EE, we suggest that EE-induced cell survival in the DG involves
      cortical restructuring as a means of promoting survival. We conclude that EE and
      VEx lead to an increase in overall hippocampal neurogenesis via dissociable
      pathways, and should therefore, be considered distinct interventions with regard
      to hippocampal plasticity and associated behaviors.

PMID- 16411244
TI  - Stress and adult neurogenesis.
AB  - Stress hormones have potent growth-inhibiting effects on a variety of peripheral
      tissues. Consistent with this general function, stress has been shown to inhibit
      cell proliferation and, ultimately, neurogenesis in the hippocampus. This effect
      appears to be common across mammalian species, life stages, and most types of
      stressors. Although some evidence points to a role for glucocorticoids in
      mediating this effect, contradictory data exist. This review considers the
      growing literature on this subject with specific emphasis on paradoxical findings
      and the role of glucocorticoids in modulating adult neurogenesis.

PMID- 16411243
TI  - Input source and strength influences overall firing phase of model hippocampal
      CA1 pyramidal cells during theta: relevance to REM sleep reactivation and memory
      consolidation.
AB  - In simulation studies using a realistic model CA1 pyramidal cell, we accounted
      for the shift in mean firing phase from theta cycle peaks to theta cycle troughs
      during rapid-eye movement (REM) sleep reactivation of hippocampal CA1 place cells
      over several days of growing familiarization with an environment (Brain Res
      855:176-180). Changes in the theta drive phase and amplitude between proximal and
      distal dendritic regions of the cell modulated the theta phase of firing when
      stimuli were presented at proximal and distal dendritic locations. Stimuli at
      proximal dendritic sites (proximal to 100 microm from the soma) invoked firing
      with a significant phase preference at the depolarizing theta peaks, while distal
      stimuli (>290 microm from the soma) invoked firing at hyperpolarizing theta
      troughs. The input location-related phase preference depended on active dendritic
      conductances, a sufficient electrotonic separation between input sites and theta
      induced subthreshold membrane potential oscillations in the cell. The simulation
      results predict that the shift in mean theta phase during REM sleep cellular
      reactivation could occur through potentiation of distal dendritic (temporo
      ammonic) synapses and depotentiation of proximal dendritic (Schaffer collateral)
      synapses over the course of familiarization.

PMID- 16411245
TI  - Aerobic decolorization and detoxification of a disperse dye in textile effluent
      by a new isolate of Bacillus sp.
AB  - A number of aerobic species capable of decolorizing some of the dyes in a textile
      mill effluent were isolated. One of the isolates was able to decolorize Terasil
      black dye under aerobic conditions in the presence of an exogenous carbon source
      after 5 days. Glucose or starch (%1 ea) are essential for decolorization but the
      process proceeds faster in the presence of 0.5% yeast extract. Results of the
      BOD(5) show that the untreated effluent samples have a low BOD value, whereas
      treated samples show an initial increase in BOD up to 15 days followed by a
      decrease after 20 days. FT-IR and GC-MS data also reveal that the initial
      components in the untreated effluent disappear after 20 days of treatment,
      confirming biodegradation of the dye. Phytotoxicity tests on the untreated
      effluent samples using the seeds of Lens orientalis, Triticum aestivum, and
      Triticum boeoticum indicate that the first one is the most sensitive while the
      last one is the most resistant. On the other hand the treated effluent allows 90%
      germination in Triticum boeoticum seeds and 100% germination in the other two.

PMID- 16411246
TI  - Cortical network for representing the teeth and tongue in primates.
AB  - Sensory information from the tongue and teeth is used to evaluate and distinguish
      food and nonfood items in the mouth, reject some and masticate and swallow
      others. While it is known that primates have a complex array of 10 or more
      somatosensory areas that contribute to the analysis of sensory information from
      the hand, less is known about what cortical areas are involved in processing
      information from receptors of the tongue and teeth. The tongue contains taste
      receptors, as well as mechanoreceptors. Afferents from taste receptors and
      mechanoreceptors of the tongue access different ascending systems in the
      brainstem. However, it is uncertain how these two sources of information are
      processed in cortex. Here the parts of somatosensory areas 3b, 3a, and
      presumptive 1 that represent the mechanoreceptors of the teeth and tongue are
      identified, and evidence is presented that the representations of the tongue also
      get information from the taste nucleus of the thalamus, VPMpc. As areas 3b, 3a,
      and 1 project to other areas of somatosensory cortex, and those areas to
      additional areas, some or all of the currently defined somatosensory areas of
      cortex may be involved in processing gustatory, as well as tactile, information
      from the tongue and thus have a role in the biologically important function of
      evaluating food in the mouth.

PMID- 16411247
TI  - Imaging, anatomical, and molecular analysis of callosal formation in the
      developing human fetal brain.
AB  - A complex set of axonal guidance mechanisms are utilized by axons to locate and
      innervate their targets. In the developing mouse forebrain, we previously
      described several midline glial populations as well as various guidance molecules
      that regulate the formation of the corpus callosum. Since agenesis of the corpus
      callosum is associated with over 50 different human congenital syndromes, we
      wanted to investigate whether these same mechanisms also operate during human
      callosal development. Here we analyze midline glial and commissural development
      in human fetal brains ranging from 13 to 20 weeks of gestation using both
      diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our
      combined radiological and histological studies, we demonstrate the morphological
      development of multiple forebrain commissures/decussations, including the corpus
      callosum, anterior commissure, hippocampal commissure, and the optic chiasm.
      Histological analyses demonstrated that all the midline glial populations
      previously described in mouse, as well as structures analogous to the subcallosal
      sling and cingulate pioneering axons, that mediate callosal axon guidance in
      mouse, are also present during human brain development. Finally, by Northern blot
      analysis, we have identified that molecules involved in mouse callosal
      development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1, and GAP-43, are all
      expressed in human fetal brain. These data suggest that similar mechanisms and
      molecules required for midline commissure formation operate during both mouse and
      human brain development. Thus, the mouse is an excellent model system for
      studying normal and pathological commissural formation in human brain
      development.

PMID- 16411248
TI  - Whisker maps in marsupials: nerve lesions and critical periods.
AB  - In the wallaby, whisker-related patterns develop over a protracted period of
      postnatal maturation in the pouch. Afferents arrive simultaneously in the
      thalamus and cortex from postnatal day (P) 15. Whisker-related patterns are first
      seen in the thalamus at P50 and are well formed by P73, before cortical patterns
      first appear (P75) or are well developed (P85). This study used the slow
      developmental sequence and accessibility of the pouch young to investigate the
      effect of nerve lesions before afferent arrival, or at times when thalamic
      patterns are obvious but cortical patterns not yet formed. The left infraorbital
      nerve supplying the whiskers was cut at P0-93 and animals were perfused at P112
      123. Sections through the thalamus (horizontal plane) and cortex (tangential)
      were reacted for cytochrome oxidase to visualize whisker-related patterns.
      Lesions of the nerve at P2-5, before innervation of the thalamus or cortex,
      resulted in an absence of patterns at both levels. Lesions from P66-77 also
      disrupted thalamic and cortical patterns, despite the fact that thalamic patterns
      are normally well established by P73. Lesions from P82-93 resulted in normal
      thalamic and cortical patterns. Thus, despite the wallaby having clearly
      separated times for the development of patterns at different levels of the
      pathway, these results suggest a single critical period for the thalamus and
      cortex, coincident with the maturation of the cortical pattern. Possible
      mechanisms underpinning this critical period could include dependence of the
      thalamic pattern on corticothalamic activity or peripheral signals to allow
      consolidation of thalamic barreloids.

PMID- 16411249
TI  - Connecting thalamus and cortex: the role of ephrins.
AB  - The complex task of wiring up the brain during embryonic development is achieved
      by a multitude of guidance signals acting in complex combinations to drive
      growing axons to their proper targets. The somatosensory system provides an
      extensively studied model system featuring many universal mechanisms of neural
      development. In rodents, it constitutes an important model to study how precise
      topographic connections are achieved. Recent evidence suggests that the
      Eph/ephrin family of guidance molecules is of pivotal importance for the
      development of the somatosensory system. Members of Eph/ephrin family are thought
      to be involved in the global presorting of thalamic axons projecting to the
      cortex, in labeling specific cortical areas for innervation, in providing
      topographic cues within the target area, and in distinguishing cortical layers
      for intracortical wiring. The Eph/ephrin system also seems to contribute to the
      formation of specific corticothalamic feedback projections. So far, the functions
      of only a few members of the Eph/ephrin family have been examined, but expression
      analysis indicates complex combinatorial effects of these signaling molecules.
      Understanding the Eph/ephrin wiring code is expected to yield new insights into
      the development and plasticity of brain circuits involved in higher functions.

PMID- 16411250
TI  - Determining molecular structures and conformations directly from electron
      diffraction using a genetic algorithm.
AB  - A global optimization strategy, based upon application of a genetic algorithm
      (GA), is demonstrated as an approach for determining the structures of molecules
      possessing significant conformational flexibility directly from gas-phase
      electron diffraction data. In contrast to the common approach to molecular
      structure determination, based on trial-and-error assessment of structures
      available from quantum chemical calculations, the GA approach described here does
      not require expensive quantum mechanical calculations or manual searching of the
      potential energy surface of the sample molecule, relying instead upon simple
      comparison between the experimental and calculated diffraction pattern derived
      from a proposed trial molecular structure. Structures as complex as all-trans
      retinal and p-coumaric acid, both important chromophores in photosensing
      processes, may be determined by this approach. In the examples presented here, we
      find that the GA approach can determine the correct conformation of a flexible
      molecule described by 11 independent torsion angles. We also demonstrate
      applications to samples comprising a mixture of two distinct molecular
      conformations. With these results we conclude that applications of this approach
      are very promising in elucidating the structures of large molecules directly from
      electron diffraction data.

PMID- 16411251
TI  - Magnetic resonance angiography of collateral vessel growth in a rabbit femoral
      artery ligation model.
AB  - Collateral vessel growth was visualized in a rabbit femoral artery ligation model
      by serial contrast-enhanced magnetic resonance angiography (MRA) at 1.5 T in
      comparison with X-ray angiography (XRA). XRA and MRA were performed directly
      after femoral artery ligation (day 0+) and after 7 and 21 days. XRA (in-plane
      resolution, 0.3x0.3 mm) was performed with arterial catheterization for fast
      injection of iodinated contrast agent just proximal to the aortic bifurcation.
      MRA (in-plane, 0.6x0.6 mm) was performed at 1.5 T with a five-element phased
      array coil and slow injection of gadolinium-based MR contrast agent into an ear
      vein. Collateral vessel scores on two-dimensional XRA projections and on three
      dimensional digitally subtracted rotational MRA maximum intensity projections
      were obtained by two observers and compared. Collateral vessel counts and minimal
      detectable vessel diameters for MRA and XRA were combined in a computational flow
      model to interpret differences in spatial detection limits between imaging
      modalities in terms of flow. Collateral vessel scores were significantly higher
      in the ligated limb at day 7 (P < 0.05) and more so at day 21 (P < 0.001), in
      comparison with day 0+ or in the non-ligated control limb on both XRA and MRA.
      Significantly more (smaller) vessels were visualized with XRA than with MRA,
      particularly on day 21 (P < 0.05). Inter-observer agreement was high for both XRA
      (kappa = 0.82) and MRA (kappa = 0.78). The flow model showed that collateral
      vessels with diameters > 0.3 mm scored by XRA as well as MRA represent nearly
      100% of the total blood flow, whereas smaller (0.1-0.3 mm diameter) vessels that
      can only be detected with XRA contribute little to the blood flow. Serial
      contrast-enhanced MRA can non-invasively visualize sub-millimeter collateral
      vessels that represent nearly 100% of the restored blood flow, in a femoral
      artery ligation model.

PMID- 16411252
TI  - Assessment of anti-metastatic drug efficacy via localization and quantification
      of ex vivo murine bone tumor load using high-throughput MRI T1 parametric
      analysis.
AB  - MRI methods show great utility for assessing the growth of tumors metastasized to
      bone in clinical studies. However, preclinical MRI methods in rodents do not
      translate well to high-throughput studies of bone tumors, especially for early
      stage tumors typically examined in pharmaceutical discovery efforts. To overcome
      these limitations, an ex vivo MR T1 parametric mapping method has been developed
      to measure metastasized bone tumor load in murine long bones. This method has
      been used to assess the therapeutic efficacy of SU11248, a multi-targeted
      inhibitor with demonstrated anti-tumor activity and reduction of bone loss, in a
      murine model of metastasized breast tumor cells. The results show precise
      localizations of relative tumor loads within the bones and reveal significant
      differences between SU11248-treated and untreated animal groups. The procedures
      were optimized for simultaneous, high-throughput parallel image acquisition of
      MRI data for 30 samples and included an automated segmentation method for image
      processing. The merits of this T1 parametric mapping method are compared with
      clinical T1-weighted MRI methods, histopathology and bioluminescence imaging of
      the same murine bone tumor model.

PMID- 16411253
TI  - Cell labeling for magnetic resonance imaging with the T1 agent manganese
      chloride.
AB  - There is growing interest in using MRI to track cellular migration. To date, most
      work in this area has been performed using ultra-small particles of iron oxide.
      Immune cells are difficult to label with iron oxide particles. The ability of
      adoptively infused tumor specific T cells and N cells to traffic to the tumor
      microenvironment may be a critical determinant of their therapeutic efficacy. We
      tested the hypothesis that lymphocytes and B cells would label with MnCl2 to a
      level that would allow their detection by T1-weighted MRI. Significant signal
      enhancement was observed in human lymphocytes after a 1 h incubation with 0.05
      1.0 mM MnCl2. A flow cytometry-based evaluation using propidium iodide and
      Annexin V staining showed that lymphocytes did not undergo apoptosis or necrosis
      immediately after and 24 h following a 1 h incubation with up to 1.0 mM MnCl2.
      Importantly, NK cells and cytotoxic T cells maintained their in vitro killing
      capacity after being incubated with up to 0.5 mM MnCl2. This is the first report
      to describe the use of MnCl2 to label lymphocytes. Our data suggests MnCl2 might
      be an alternative to iron oxide cell labeling for MRI-based cell migration
      studies.

PMID- 16411254
TI  - Directed evolution of enantioselective enzymes: iterative cycles of CASTing for
      probing protein-sequence space.

PMID- 16411255
TI  - Mechanism of nitrate reduction by Desulfovibrio desulfuricans nitrate reductase-
      a theoretical investigation.
AB  - The oxidative half-reaction of oxygen atom transfer from nitrate to an Mo(IV)
      complex has been investigated at various levels of theory. Two models have been
      used to simulate the enzyme active site. In the second, more advanced model,
      additional amino acid residues capable of significantly affecting the catalytic
      efficiency of the enzyme were included. B3LYP/6-31+G*, ONIOM, and orbital-free
      embedding approaches have been used to construct the potential energy profile and
      to qualitatively compare the results of a QM/MM study with those obtained by a
      full quantum mechanical strategy. The study has confirmed the utility of the
      orbital-free embedding method in the description of enzymatic processes.

PMID- 16411256
TI  - Complex wurtzite ZnSe microspheres with high hierarchy and their optical
      properties.
AB  - Complex wurtzite ZnSe microspheres with hierarchical fractal structure and
      showing strong quantum-size effects can be prepared easily by a mild solvothermal
      reaction in a diethylenetriamine (DETA)-deionized water (DIW) binary solution.
      The ZnSe microspheres are made up of nanosheets, each formed by the face-to-face
      pairing of two individual nanosheets. In addition, high-order, flowerlike
      hierarchical structures are formed by the attachment of flexible, uniform
      nanofibers to the exposed faces of each nanosheet pair. The surface morphology of
      the nanosheets changed as reaction time increased and the detailed phase
      transformation and shape-evolution processes were studied. This approach could
      provide an effective strategy for tuning the electronic and optical properties of
      semiconductors, with special advantages over the traditional high-temperature
      approach, and could be extended to access other semiconductor materials with
      unusual morphologies and structures.

PMID- 16411257
TI  - Spatial extent of the singlet and triplet excitons in luminescent angular-shaped
      transition-metal diynes and polyynes comprising non-pi-conjugated group 16 main
      group elements.
AB  - A novel approach based on conjugation interruption has been developed and is
      presented for a series of luminescent and thermally stable chalcogen-bridged
      platinum(II) polyyne polymers trans-[{-Pt(PBu3)2C[triple
      bond]C(C6H4)E(C6H4)C[triple bond]C-}n] (E = O, S, SO, SO2). Particular attention
      was focused on the photophysical properties of these Group 10 polymetallaynes and
      comparison was made to their binuclear model complexes trans
      [Pt(Ph)(PEt3)2C[triple bond]C(C6H4)E(C6H4)C[triple bond]CPt(Ph)(PEt3)2] and their
      closest Group 11 gold(I) and Group 12 mercury(II) neighbours, [MC[triple
      bond]C(C6H4)E(C6H4)C[triple bond]CM] (M = Au(PPh3), HgMe; E = O, S, SO, SO2). The
      regiochemical structures of these angular-shaped molecules were studied by NMR
      spectroscopy and single-crystal X-ray structural analyses. Upon photoexcitation,
      each one has an intense purple-blue fluorescence emission near 400 nm in dilute
      fluid solutions at room temperature. Harvesting of the organic triplet emissions
      harnessed through the strong heavy-atom effects of Group 10-12 transition metals
      was studied in detail. These metal-containing aryleneethynylenes spaced by
      chalcogen units were found to have large optical gaps and high-energy triplet
      states. The influence of metal- and chalcogen-based conjugation interrupters on
      the intersystem crossing rate and on the spatial extent of the lowest singlet and
      triplet excitons was fully elucidated. We discuss and compare the phosphorescence
      spectra of these transition-metal diynes and polyynes in terms of the nature of
      the metal centre, conjugated chain length and Group 16 spacer unit. Our work here
      indicates that high-energy triplet states in these materials intrinsically give
      rise to very efficient phosphorescence with fast radiative decays and one could
      readily observe room-temperature phosphorescence for the platinum polyynes.

PMID- 16411258
TI  - A stacking interaction between a bridging hydrogen atom and aromatic pi density
      in the n-B18H22-benzene system.
AB  - The structures of n-B18H22 and of n-B18H22 x C6H6 were determined by single
      crystal X-ray analysis at -60 degrees C. The geometry of the boron cluster itself
      does not seem to be appreciably affected by solvation. There does, however,
      appear to be an unusual interaction of a polyborane bridging hydrogen atom with
      the benzene pi system, giving rise to an extended stacked structure. The 1H{11B}
      spectrum of n-B18H22 in [D6]benzene differs from that in [D12]cyclohexane most
      noticeably in the bridging proton region. Upon moving from the aliphatic to the
      aromatic solvent, the greatest increase in shielding was for the signal
      corresponding to the bridge hydrogen atom that interacts with the pi system of
      benzene; the signal was shifted upfield by 0.49 ppm. Density functional theory
      calculations were performed on 1:1 and 2:1 complexes of the n-B18H22 unit with
      benzene.

PMID- 16411259
TI  - Kinetic energy release of C70(+) and its endohedral cation N@C70(+): activation
      energy for N extrusion.
AB  - Unimolecular decomposition of C70(+) and its endohedral cation N@C70(+) were
      studied by high-resolution mass-analyzed ion kinetic energy (MIKE) spectrometry.
      Information on the energetics and dynamics of these reactions was extracted.
      C70(+) dissociates unimolecularly by loss of a C2 unit, whereas N@C70(+) expels
      the endohedral N atom. Kinetic energy release distributions (KERDs) in these
      reactions were measured. By use of finite heat bath theory (FHBT), the binding
      energy for C2 emission from C70(+) and the activation energy for N elimination
      from N@C70(+) were deduced from KERDs in the light of a recent finding that
      fragmentation of fullerene cations proceeds via a very loose transition state.
      The activation energy measured for N extrusion from N@C70(+) was found to be
      lower than that for C2 evaporation, higher than the value from its neutral
      molecule N@C70 obtained on the basis of thermal stability measurements, and
      coincident with the theoretical value. The results provide confirmation that the
      proposed extrusion mechanism in which the N atom escapes from the cage via
      formation of an aza-bridged intermediate is correct.

PMID- 16411260
TI  - Effective controlled release of captopril by silylation of mesoporous MCM-41.
AB  - The release of the water-soluble drug Captopril is controlled by tailoring the
      surface properties of mesoporous silica via stepwise silylation. The degree of
      silylation is manipulated by adjusting the initial concentration of silylanizing
      reagent (trimethylchlorosilane, TMCS). The silylanized and drug-loaded samples
      are characterized by powder X-ray diffraction, Fourier transform IR spectroscopy,
      N2 adsorption and desorption, 29Si cross-polarization magic angle spinning NMR
      spectroscopy, and transmission electron microscopy. The drug-loading amount is
      correlated to the Brunauer-Emmett-Teller surface area and surface
      hydrophilicity/hydrophobicity of the mesoporous silica material, while drug
      release profiles can be controlled by tailoring the surface properties and pore
      size.

PMID- 16411261
TI  - Probing the acidity of p-substituted phenols in the excited state: electronic
      spectroscopy of the p-cyanophenol-water cluster.
AB  - The hydrogen bond structure of the p-cyanophenol-water cluster has been
      determined in the ground and first excited electronic state by rotationally
      resolved UV spectroscopy. The water molecule is trans-linearly bound to the
      hydroxy group of the p-cyanophenol moiety, with hydrogen bond distances
      considerably shorter in both electronic states than in the similar phenol-water
      cluster. The structure of the cluster has been elucidated by ab initio
      calculations at various levels of theory and compared to the experimental
      findings. The barriers to internal rotation of the water moiety were determined
      experimentally to be 275 and 183 cm(-1) for the ground and excited state,
      respectively. Hydrogen bond distances and the energy barrier to water torsion
      correlate with the pK(a) values of different substituted phenols for both
      electronic states.

PMID- 16411262
TI  - Chair, boat and twist conformation of dodecamethylcyclohexasilane and
      undecamethylcyclohexasilane: a combined DFT and Raman spectroscopic study.
AB  - The conformations of dodecamethylcyclohexasilane Si6Me12 and
      undecamethylcyclohexasilane Si6Me11H have been investigated by ab initio
      calculations employing the B3LYP density functional with a 6-31+G(d) basis set.
      Local minima as well as transition structures were calculated with imposed
      symmetry constraints. For Si6Me12, three unique minima, which correspond to the
      chair, twist and boat conformations were located with relative zero-point
      vibration-corrected energies of 0.0, 7.8 and 11.4 kJ mol(-1). A half-chair
      conformation with four coplanar silicon atoms connects the chair and twisted
      minima via an energy barrier of 16.0 and 8.2 kJ mol(-1), respectively. A second
      transition structure with a barrier of 3.9/0.3 kJ mol(-1) connects the twist with
      the boat structure. Solution Raman spectra of Si6(CH3)12 and Si6(CD3)12 fully
      corroborate these results. Below -40 degrees C, the symmetric SiSi ring breathing
      vibration is a single line, which develops a shoulder (originating from the twist
      conformer) at longer wavelengths whose intensity increases with increasing
      temperature. From a Van't Hoff plot, the chair/twist enthalpy difference is 6.6+/
      1.5 kJ mol(-1) for Si6(CH3)12 and 6.0+/-1.5 kJ mol(-1) for Si6(CD3)12, which is
      in reasonable agreement with the ab initio results. Due to the low barrier, the
      boat conformation cannot be observed, because either the lowest torsional
      vibration level lies above it or a rapid interconversion between the twist and
      boat conformations occurs, resulting in averaged Raman spectra. For Si6Me11H, six
      local minima were located. The chair with the hydrogen atom in the axial position
      (axial chair) is the global minimum, followed by the equatorial chair (+1.9 kJ
      mol(-1)) and the three twist conformers (+5.3, +8.0 and +8.1 kJ mol(-1)). The
      highest local minimum (+11.9 kJ mol(-1)) is a C(s) symmetric boat with the
      hydrogen atom in the equatorial position. Two possible pathways for the chair-to
      chair interconversion with barriers of 13.9 and 14.5 kJ mol(-1) have been
      investigated. The solution Raman spectra in the SiSi ring breathing region
      clearly show that below -50 degrees C only the axial and equatorial chairs are
      present, with an experimental deltaH-value of 0.46 kJ mol(-1). With increasing
      temperature a shoulder develops which is attributed to the combined twist
      conformers. The experimental deltaH-value is 6.9 kJ mol(-1), in good agreement
      with the ab initio results. Due to the low interconversion barriers, the various
      twist conformers cannot be detected separately.

PMID- 16411263
TI  - Controlling wettability and photochromism in a dual-responsive tungsten oxide
      film.

PMID- 16411264
TI  - Two-dimensional hierarchical self-assembly of one-handed helical polymers on
      graphite.

PMID- 16411265
TI  - The local structure of ionic liquids: cation-cation NOE interactions and
      internuclear distances in neat [BMIM][BF4] and [BDMIM][BF4].

PMID- 16411266
TI  - Proteomic analysis of the effect of Antrodia camphorata extract on human lung
      cancer A549 cell.
AB  - Antrodia camphorata (niu-chang-chih) is a fungus native to Taiwan that is
      believed to be effective in preventing diseases. This study demonstrates that 0.2
      2% v/v ethanol extracts of A. camphorata cultivated by solid-state fermentation
      (SACE) can effectively impede the proliferation of human non-small cell lung
      carcinoma A549 cells but not primary human fetal lung fibroblast MRC-5. The
      results of apoptotic analyses implicate that SACE might trigger the apoptosis in
      the A549 cells by inducing endoplasmic reticulum stress. Two-dimensional gel maps
      of non-treated and treated A549 cells were compared using PDQUEST analytical
      software to discover five statistically significant twofold or above-twofold
      differentially-expressed protein spots. The five protein spots that were
      significantly de-regulated were chosen for subsequent identification by high
      performance liquid chromatography electro-spray tandem mass spectrometry. The
      five proteins were later identified as human galectin-1, human eukaryotic
      translation initiation factor 5A, human Rho GDP dissociation inhibitor alpha,
      human calcium-dependent protease small subunit and human annexin V. All five
      proteins were confirmed to be down-regulated by Western blotting. The analytical
      results of this study help to provide insight into the effect of SACE on the gene
      expression of the tumor cells.

PMID- 16411267
TI  - Autumn 2005 Workshop of the Human Proteome Organisation Proteomics Standards
      Initiative (HUPO-PSI) Geneva, September, 4-6, 2005.
AB  - The autumn workshop of the Proteomics Standards Initiative of the Human
      Proteomics Organisation met to further advance the development of the existing
      standards in the fields of molecular interactions and mass spectrometry. In
      addition, new areas were addressed, in particular developing standards for the
      description and exchange of data from gel electrophoresis experiments. The
      General Proteomics Standards group is now working closely with the FuGE
      (Functional Genomics Experiment) efforts to define a general standard in which to
      encode data that will enable a systems biology approach to data analysis. Common
      to all these efforts is the field of protein modifications, and work has been
      initiated to establish an ontology in this field that can be used by both workers
      in the field of proteomics and the wider scientific community.

PMID- 16411268
TI  - Peptidomics: bridging the gap between proteome and metabolome.
AB  - Studies of naturally occurring peptides and protein profiling by 'classical'
      proteomics are linked by common analytical objectives and methodologies. The
      first international workshop "Peptidomics: methods and applications" held on 6
      7th September 2005 at Royal Holloway University of London confirmed that the
      science of peptidomics is a rapidly developing activity of high interest to both
      academia and industry. This meeting featured talks by over 20 leading
      international scientists detailing methods and typical applications, including
      newly-developed capabilities for protein and peptide analyses. It provided a
      definition of the scope of the subject in terms of current and future
      technologies together with applications ranging from studies of defined
      biological extracts to complete ecosystems. The proceedings of this meeting,
      speakers' contact details and other relevant information can be accessed at:
      www.rhul.ac.uk/biosci/meetings.

PMID- 16411269
TI  - Screening of a supramolecular catalyst library in the search for selective
      catalysts for the asymmetric hydrogenation of a difficult enamide substrate.

PMID- 16411270
TI  - Study on separation of aristolochic acid I and II by micellar electrokinetic
      capillary chromatography and competition mechanism between SDS and beta
      cyclodextrin.
AB  - In this study, a rapid MEKC method using 40 mM sodium borate buffer containing 50
      mM SDS as surfactant was developed for the analysis of aristolochic acid (AA) in
      Aristolochia plants. Baseline separation of AA-I and AA-II was achieved within 3
      min with high separation efficiency, satisfactory sensitivity, repeatability, and
      recovery. Resolution between AA-I and AA-II is above 5 and great performance with
      higher than 200,000 theoretical plate numbers was obtained. The detection limits
      (based on 3 S/N) were both 1.0 microg/mL. Two kinds of AA in 35 herbal samples of
      Aristolochia plants were successfully determined. The competition mechanism
      between beta-CD and SDS was also investigated by changing the content ratio of
      beta-CD and SDS.

PMID- 16411271
TI  - Determination of biogenic amines in HeLa cell lysate by 6-oxy-(N-succinimidyl
      acetate)-9-(2'-methoxycarbonyl) fluorescein and micellar electrokinetic capillary
      chromatography with laser-induced fluorescence detection.
AB  - An MEKC-LIF method using 6-oxy-(N-succinimidyl acetate)-9-(2'-methoxy-carbonyl)
      fluorescein (SAMF) newly synthesized in our lab as a labeling reagent for the
      separation and determination of eight typical biogenic amines was proposed. After
      careful study of the derivatization condition such as pH value, reagent
      concentration, temperature, and reaction time, derivatization reaction was
      accomplished as quickly as 10 min with stable yield. Optimal separation of SAMF
      labeled amines was achieved with a running buffer (pH 9.3) containing 30 mM boric
      acid, 25 mM SDS, and 20% v/v ACN. The proposed method allowed biogenic amines to
      be determined with LODs as low as 0.25-2.5 nmol/L and RSD values from 0.4 to
      4.5%. The present method has been successfully used to monitor biogenic amines in
      HeLa cells and fish samples. This study exploits the potential of MEKC-LIF with
      SAMF labeling as a tool for monitoring biogenic amines involved in complex
      physiological and behavioral processes in various matrices.

PMID- 16411272
TI  - Separation and quantitation of the four stereoisomers of itraconazole in
      pharmaceutical formulations by electrokinetic chromatography.
AB  - The four stereoisomers of itraconazole were resolved for the first time by EKC
      using a CD as chiral selector. A study on the enantiomeric separation ability of
      different neutral CDs was carried out. Heptakis-2,3,6-tri-O-methyl-beta-CD was
      shown to provide the highest values for the enantiomeric resolution. The
      influence of some experimental conditions, such as pH, chiral selector
      concentration, and temperature, on the enantiomeric separation was also studied.
      The use of a 100 mM phosphate buffer (pH 2.5), 30 mM in heptakis-2,3,6-tri-O
      methyl-beta-CD together with an applied voltage of 30 kV and a temperature of 20
      degrees C enabled the separation of the enantiomers of itraconazole with high
      resolutions (Rs > 3.0). Finally, the method was validated and successfully
      applied to the quantitation of itraconazole in three pharmaceutical formulations.

PMID- 16411273
TI  - Capillary electrochromatography of biologically relevant flavonoids.
AB  - Flavonoids were separated utilizing CEC technique. Baseline separation of
      biologically relevant flavonoids was obtained using a 100 microm ID fused-silica
      capillary filled with 3 microm Silica-C18 material and an optimized mobile phase
      comprising of 20 mM Tris-HCl (pH 6.5), ACN and water at a ratio of 10/40/50
      v/v/v. Separations were carried out at 25 kV and a column temperature of 25
      degrees C. The influence of relevant parameters for the CEC separation, such as
      buffer concentration, pH, separation voltage, and ACN concentration, was
      investigated and optimized. Dependencies of the electroendoosmotic flow (EOF) on
      these parameters and effects on the resolution of the analytes were studied.
      During analyses the solvents used for dissolving the samples turned out to have
      significant effects on the separation of flavonoids. The optimized system was
      then successfully used for the separation of the flavonoids epicatechin,
      myricetin, quercetin, naringenin, and hesperetin. CEC turned out to be a useful
      complementary tool for the economic analysis of flavonoids in addition to common
      HPLC, muHPLC, and CE methodologies. This method can be used for real applications
      in phytomics.

PMID- 16411274
TI  - Rapid determination of acyclovir in plasma and cerebrospinal fluid by micellar
      electrokinetic chromatography with direct sample injection and its clinical
      application.
AB  - A simple MEKC with UV detection at 254 nm for analysis of acyclovir in plasma and
      in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment
      is described. The separation of acyclovir from biological matrix was performed at
      25 degrees C using a BGE consisting of Tris buffer with SDS as the electrolyte
      solution. Several parameters affecting the separation of the drug from biological
      matrix were studied, including the pH and concentrations of the Tris buffer and
      SDS. Using dyphylline as an internal standard, the linear ranges of the method
      for the determination of acyclovir in plasma and in CSF all exceeded the range of
      2-50 microg/mL; the detection limit of the drug in plasma and in CSF (S/N = 3;
      injection 3.45 kPa, 5 s) was 1.0 microg/mL. The applicability of the proposed
      method for determination of acyclovir in plasma and CSF collected at 8 h after
      intravenous administration of 500 mg acyclovir (Zovirax) in two patients with
      herpes simplex encephalitis was demonstrated.

PMID- 16411275
TI  - An on-column derivatization method for the determination of the enantiomeric
      excess of chiral primary amines via indirect enantioseparation by micellar
      electrokinetic chromatography.
AB  - A method used for determining the enantiomeric excess (ee) value of chiral amino
      compounds by MEKC is described. In this method, the plug-plug type
      electrophoretic medicated microanalysis technique was employed to convert the
      enantiomers of chiral amino compounds into their diastereomers through an on
      column derivatization with o-phthaldialdehyde and the chiral reagent N-acetyl-L
      cysteine. Afterwards, the resulting diastereomers were easily separated with a
      nonchiral MEKC approach. The on-column derivatization conditions and the
      separation conditions were optimized and the method was validated with five
      chiral amino compounds. The present method can be used for assaying the ee value
      of chiral amino compound with various structural features, especially for those
      that have no UV chromophore. Therefore, the method can be potentially used for
      screening or evaluation of the asymmetric catalysts developed by the
      combinatorial chemistry. In this case, the ee values of chiral products with
      various structures need to be measured; however, this is difficult for direct
      chiral separation approach due to the fact that the chiral selectivity is
      strongly dependent on the structure of the analytes. The method is simple,
      reliable, and automatic.

PMID- 16411276
TI  - Metallomesogenic stationary phase for open-tubular capillary
      electrochromatography.
AB  - A synthetic coppermesogenic polymer is prepared and then covalently bonded to the
      siloxane-based deactivated column as the stationary phases of open-tubular CEC
      with essentially high phase ratio. The EOF generated from the modified phase is
      surveyed through conventional aqueous buffers and hydroorganic mobile phases.
      Zeta potentials, which are computed from the EOF data and the ratio of dielectric
      constant to viscosity, are plotted as a function of pH, ionic molarity, and
      compositional range. These plots responsible for the electroosmotic
      characteristic of the bonded phases are found to be like those of bare fused
      silica or deactivated columns through decreasing or increasing the ACN content in
      the mobile phase, respectively. This two-phase characteristic is basically
      derived from the polymeric configuration with carboxylato ligands attached onto
      the polysiloxane backbone. Phthalates and amino acids are suitable probes to
      examine the two phenomena, more-polar and less-polar mediums, respectively, and
      to judge whether the chromatographic retention is the major source of separation
      mechanism. With the mixing modes of Lewis acid-base interaction, dispersive
      force, and shape discrimination, the chromatographic partition adequately
      accomplishes the uneasily resolved separations by only CZE mode, although the
      electrophoretic migration is truly somewhat involved.

PMID- 16411277
TI  - Investigation of vesicle electrokinetic chromatography as an in vitro assay for
      the estimation of intestinal permeability of pharmaceutical drug candidates.
AB  - As the pharmaceutical industry continues the daunting search for novel drug
      candidates, there remains a need for rapid screening methods not only for
      biological activity, but for physiochemical properties as well. It is invaluable
      that adequate model systems for absorption and/or bioavailability be developed
      early in the drug evaluation process to avoid the loss of promising compounds
      late in development. The focus of this paper is the use of vesicle EKC (VEKC) as
      a high-throughput, easy, cost-effective, and predictive model for the passive
      transcellular diffusion of drug candidates in the intestinal epithelium. Vesicles
      are large aggregates of molecules containing a spherical bilayer structure
      encapsulating an internal cavity of solvent. It is this bilayer structure that
      makes vesicles attractive as model membranes. In this study, vesicles were
      synthesized from both phospholipids and surfactant aggregates, and then employed
      as pseudostationary phases in EKC (VEKC). The interaction of drug molecules with
      vesicles in EKC was then used as the basis for an in vitro assay to evaluate
      passive diffusion. The VEKC technique showed a statistical correlation between
      the retention of drug candidates using surfactant and phospholipid vesicles and
      passive diffusion data (log Pow and colon adenocarcinoma). VEKC analysis offers
      high-throughput capabilities due to the short run times, low sample, and solvent
      volumes necessary, as well as instrument automation. However, due to the
      complexity of drug absorption in the intestine, difficulty arises when a single
      in vitro model is used to predict in vivo absorption characteristics. Therefore,
      the retention of drug candidates using VEKC in conjunction with other
      permeability prediction methods can provide a primary screen for a large number
      of drug candidates early in the drug discovery process with minimal resources.

PMID- 16411278
TI  - Dynamic process of phospholipid-protein interaction studied by capillary
      isoelectric focusing with whole-column imaging detection.
AB  - Liposomes are vesicles formed by the aggregation of amphiphilic phospholipid
      molecules, which can mimic natural cell membranes. Interaction between liposome
      and protein is important for the structure and function of natural cell
      membranes. In this study, a CIEF method with whole-column imaging detection was
      developed for monitoring the dynamic process of phospholipid-protein
      interactions. The CIEF profiles at successive interaction times clearly displayed
      the formation of the different conjugates between phospholipid and protein at
      different stages. Due to the diversity of the chemical and physical properties of
      targeted proteins in this study (trypsin inhibitor, beta-lactoglobulin B,
      phosphorylase b, and trypsinogen), different dynamic processes of phospholipid
      protein interactions were exhibited. The type of phospholipids played an
      important role in the dynamic process of phospholipid-protein interaction, as
      noted by the use of zwitterionic phospholipid (phosphatidylcholine) and acidic
      phospholipid (phosphatidylserine). Mechanisms involved in these interactions were
      discussed by monitoring the dynamic processes in this study.

PMID- 16411279
TI  - Solving the clogging problem: precipitate-forming reactions in flow.

PMID- 16411281
TI  - Childhood trauma is taken to heart.

PMID- 16411280
TI  - Quantification of prostate MRSI data by model-based time domain fitting and
      frequency domain analysis.
AB  - This paper compares two spectral processing methods for obtaining quantitative
      measures from in vivo prostate spectra, evaluates their effectiveness, and
      discusses the necessary modifications for accurate results. A frequency domain
      analysis (FDA) method based on peak integration was compared with a time domain
      fitting (TDF) method, a model-based nonlinear least squares fitting algorithm.
      The accuracy of both methods at estimating the choline + creatine + polyamines to
      citrate ratio (CCP:C) was tested using Monte Carlo simulations, empirical phantom
      MRSI data and in vivo MRSI data. The paper discusses the different approaches
      employed to achieve the quantification of the overlapping choline, creatine and
      polyamine resonances. Monte Carlo simulations showed induced biases on the
      estimated CCP:C ratios. Both methods were successful in identifying tumor tissue,
      provided that the CCP:C ratio was greater than a given (normal) threshold. Both
      methods predicted the same voxel condition in 94% of the in vivo voxels (68 out
      of 72). Both TDF and FDA methods had the ability to identify malignant voxels in
      an artifact-free case study using the estimated CCP:C ratio. Comparing the ratios
      estimated by the TDF and the FDA, the methods predicted the same spectrum type in
      17 out of 18 voxels of the in vivo case study (94.4%).

PMID- 16411282
TI  - New injectable drug approved for type 2 diabetes.

PMID- 16411283
TI  - Beans. Make them diet regulars.

PMID- 16411284
TI  - My granddaughter has had several urinary tract infections in the past year and is
      being treated with antibiotics. I'm concerned that this could be a sign of a
      bigger problem. Should she be examined further?

PMID- 16411285
TI  - Clinical guidelines. Neurology experts rank treatments for essential tremor.

PMID- 16411286
TI  - By the way, doctor. Some brands of fresh chicken claim to be healthier because
      they're antibiotic-free.  Are the antibiotics in chicken unsafe to eat? What are
      they for?

PMID- 16411287
TI  - Chlorophyll a fluorescence induction kinetics in leaves predicted from a model
      describing each discrete step of excitation energy and electron transfer
      associated with Photosystem II.
AB  - Chlorophyll a fluorescence induction (FI) is widely used as a probe for studying
      photosynthesis. On illumination, fluorescence emission rises from an initial
      level O to a maximum P through transient steps, termed J and I. FI kinetics
      reflect the overall performance of photosystem II (PSII). Although FI kinetics
      are commonly and easily measured, there is a lack of consensus as to what
      controls the characteristic series of transients, partially because most of the
      current models of FI focus on subsets of reactions of PSII, but not the whole.
      Here we present a model of fluorescence induction, which includes all discrete
      energy and electron transfer steps in and around PSII, avoiding any assumptions
      about what is critical to obtaining O J I P kinetics. This model successfully
      simulates the observed kinetics of fluorescence induction including O J I P
      transients. The fluorescence emission in this model was calculated directly from
      the amount of excited singlet-state chlorophyll in the core and peripheral
      antennae of PSII. Electron and energy transfer were simulated by a series of
      linked differential equations. A variable step numerical integration procedure
      (ode15s) from MATLAB provided a computationally efficient method of solving these
      linked equations. This in silico representation of the complete molecular system
      provides an experimental workbench for testing hypotheses as to the underlying
      mechanism controlling the O J I P kinetics and fluorescence emission at these
      points. Simulations based on this model showed that J corresponds to the peak
      concentrations of Q(-)AQB (QA and QB are the first and second quinone electron
      acceptor of PSII respectively) and Q(-)AQ(-)B and I to the first shoulder in the
      increase in concentration of Q(-)AQ(2-)B. The P peak coincides with maximum
      concentrations of both Q(-)AQ(2-)B and PQH2. In addition, simulations using this
      model suggest that different ratios of the peripheral antenna and core antenna
      lead to differences in fluorescence emission at O without affecting fluorescence
      emission at J, I and P. An increase in the concentration of QB-nonreducing PSII
      centers leads to higher fluorescence emission at O and correspondingly decreases
      the variable to maximum fluorescence ratio (F v/F m).

PMID- 16411288
TI  - The change in length of the medial and lateral collateral ligaments during in
      vivo knee flexion.
AB  - The collateral ligaments of the knee are important in maintaining knee stability.
      However, little data has been reported on the in vivo function of the collateral
      ligaments. The objective of this study was to investigate the change in length of
      different fiber bundles of the medial collateral ligament (MCL), deep fibers of
      the MCL (DMCL) and the lateral collateral ligament (LCL) during in vivo knee
      flexion. The knees of five healthy subjects were scanned using magnetic resonance
      imaging. These images were used to create three-dimensional models of the tibia
      and femur, including the insertions of the collateral ligaments. The MCL, DMCL,
      and LCL were each divided into three equal portions: an anterior bundle, a middle
      bundle and a posterior bundle. Next, the subjects were imaged from two orthogonal
      directions using fluoroscopy while performing a quasi-static lunge for 0 degree
      to 90 degrees of flexion. The models and fluoroscopic images were then used to
      reproduce the in vivo motion of the knee. From these models, the length of each
      bundle of each ligament was measured as a function of flexion. The length of the
      anterior bundle of the MCL did not change significantly with flexion. The length
      of the posterior bundle of the MCL consistently decreased with flexion (p less
      than 0.05). The changes in deformation of the DMCL and LCL as a function of
      flexion were similar to each other. The length of the anterior bundles increased
      with flexion and the length of the posterior bundles decreased with flexion.
      These data indicate that the collateral ligaments do not elongate uniformly as
      the knee is flexed, with different bundles becoming taut and slack. These data
      may help to provide a better understanding of the in vivo function of the
      collateral ligaments and be used to improve surgical reconstruction of the
      collateral ligaments. Furthermore, the data suggest that the different roles of
      various portions of the collateral ligaments along the flexion path should be
      considered before releasing the collateral ligaments during knee arthroplasty.

PMID- 16411289
TI  - AIDS epidemic still not under control.

PMID- 16411290
TI  - HIV drug companies must meet needs of children.

PMID- 16411291
TI  - Global Fund suspends grants to Burma.

PMID- 16411292
TI  - Azithromycin versus penicillin for early syphilis.

PMID- 16411293
TI  - Azithromycin versus penicillin for early syphilis.

PMID- 16411294
TI  - Chest X-ray quiz. Lung atelectasis.

PMID- 16411295
TI  - Cost-effectiveness of ICDs.

PMID- 16411296
TI  - [Main results of the Central Research Institute for Stomatology (CRIS) activities
      for the recent 10 years and tasks of Federal State Institution "CRIS Roszdrava:
      in modern conditions].

PMID- 16411297
TI  - [A mineral component of dental enamel in persons with different resistance to
      caries].

PMID- 16411298
TI  - [Aesthetic tooth parameter definition].

PMID- 16411299
TI  - [Innovations on the chair of prosthetic stomatology of the Omsk State Medical
      Academy].

PMID- 16411300
TI  - [Principles, methods and medicines for chronic periodontitis treatment during
      comprehensive patient rehabilitation].

PMID- 16411301
TI  - [Founder of stomatology education and training in Kazan professor P.A. Glushkov
      (the 125th anniversary of birth)].

PMID- 16411302
TI  - Cost-effectiveness of ICDs.

PMID- 16411303
TI  - Medicare and cost-effectiveness analysis.

PMID- 16411304
TI  - Medicare and cost-effectiveness analysis.

PMID- 16411305
TI  - [Spondylitis and Streptococcus viridans endocarditis].

PMID- 16411306
TI  - [Patient with tuberous sclerosis and giant renal angiomyolipomas].

PMID- 16411307
TI  - [Spontaneous expectoration of a tumour fragment].

PMID- 16411308
TI  - [What happens when antiretroviral treatment is interrupted in clinical
      practice?].

PMID- 16411309
TI  - [Primary thyroid lymphoma and Hashimoto thyroiditis].

PMID- 16411310
TI  - [Pancreas divisum. An infrequent cause of acute pancreatitis].

PMID- 16411311
TI  - [Elevation of tumor marker CA-125 in pulmonary aspergilloma].

PMID- 16411312
TI  - [Subacute endocarditis due to Actinobacillus].

PMID- 16411313
TI  - [Acute meningitis caused by Streptococcus suis: review of a case in a
      splenectomized patient].

PMID- 16411314
TI  - Aristotle's elephant and the myth of Alexander's scientific patronage.

PMID- 16411315
TI  - The staunching of Odysseus' blood: the healing power of magic.

PMID- 16411316
TI  - A Galenic argument.

PMID- 16411317
TI  - Diagnosis as narrative in ancient literature.

PMID- 16411318
TI  - Aristotle and the elephant again.

PMID- 16411319
TI  - A Homeric metaphor cluster describing teeth, tongue, and words.

PMID- 16411320
TI  - A possible physiological basis for the term urinator, "diver".

PMID- 16411321
TI  - Paralysis and akrasia in Eth. Nic. 1102, b16ff.

PMID- 16411322
TI  - Deaths in the Pan-Hellenic games: Arrachion and Creugas.

PMID- 16411323
TI  - An Epicurean interpretation of dreams.

PMID- 16411324
TI  - Democritus and the origins of moral psychology.

PMID- 16411326
TI  - Navigating the Pacific for cancer.

PMID- 16411325
TI  - Deaths in the Pan-Hellenic Games II: all combative sports.

PMID- 16411327
TI  - The death of Empedocles.

PMID- 16411328
TI  - Deaths in the Pan-Hellenic Games: addenda and corrigenda.

PMID- 16411329
TI  - Marcus Agrippa's gout.

PMID- 16411330
TI  - Aeschylus's physiology of emotions.

PMID- 16411331
TI  - Latin nenia and the Armenian Galen Dictionary.

PMID- 16411332
TI  - Aristotle's criticism of soul-division.

PMID- 16411334
TI  - Current awareness in geriatric psychiatry.

PMID- 16411333
TI  - Pseudo-Ammonius and the soul/body problem in some Platonic texts of late
      antiquity.

PMID- 16411335
TI  - Post-partum depression.

PMID- 16411336
TI  - Metabolic syndrome and schizophrenia.

PMID- 16411337
TI  - Personality subtypes and cognitive impairment in anorexia nervosa.

PMID- 16411338
TI  - Psychedelics in psychiatry.

PMID- 16411339
TI  - Theophrastus, De Vertigine, Ch. 9, and Heraclitus Fr. 125.

PMID- 16411340
TI  - [Enhanced expression of EGFR, TGF-alpha, EGF in hyperplastic parathyroid glands
      in established stage of renal failure in rats].
AB  - It was reported that the parathyroid gland hyperplasia correlated with enhanced
      co-expression of TGF-alpha and its receptor EGFR at early stages of renal
      failure. This time, we investigated the time course for EGFR and its ligands, TGF
      alpha, and EFG expression, and the influence of high-phosphorus (P) diet to EGFR
      and EGF expression, and the effect of EGFR-tyrosine kinase inhibitor (Gefitinib,
      [IRESSA; AstraZeneca]; TKI) in rat PTGs with established stage of renal failure.
      The levels of EGFR, EGF, TGF-alpha mRNA in rat PTGs were increased for the time
      periods. The serum intact PTH levels, and EGFR, EGFmRNA in rat PTGs were
      suppressed in normal-P diet group. Nuclei positive cells for PCNA in TKI group
      were suppressed. The levels of p21mRNA were increased in TKI group. These results
      suggested that the enhanced expression of EGFR, TGF-alpha and EGF participate in
      the cell proliferation of hyperplastic PTGs in established stage of renal
      failure.

PMID- 16411341
TI  - A randomized control trial of an Ultra-Short zidovudine regimen in the prevention
      of perinatal HIV transmission in rural Zimbabwe.
AB  - OBJECTIVE: To assess the practicality and effectiveness of an Ultra-Short
      zidovudine regimen for prevention of perinatal HIV transmission in rural
      Zimbabwe. DESIGN: Double-blinded placebo-controlled randomized clinical trial.
      SETTING: The Salvation Army Howard Hospital, a district hospital in rural
      Zimbabwe. SUBJECTS: 222 HIV positive pregnant women presenting for antenatal care
      prior to 36 weeks were randomized. Twenty nine women were lost to follow up.
      INTERVENTION: In the Thai regimen, mothers received zidovudine (300 mg po bid)
      from 36 weeks gestation until labour, and zidovudine (300 mg po q3h) during
      labour, and the neonates received a placebo. In the Ultra-Short regimen, the
      mothers received a placebo from 36 weeks to labour, then zidovudine (300 mg po
      q3h) in labour. The neonates received zidovudine (2 mg/kg po qid) for the first
      three days of life. MAIN OUTCOME MEASURE: Infant HIV RNA status at six weeks of
      life. RESULTS: Results were available for 90 infants from the Thai group and 89
      infants from the Ultra-Short group. Infant HIV seroconversion rates at six weeks
      of life were 18.9% (95%CI 10.8 to 27.0) with the Thai regimen, and 15.7% [95%
      Confidence Interval (CI) 8.1 to 23.4] with the Ultra-Short regimen. The upper
      bound of seroconversion in the Ultra-Short group was lower than the 25%
      seroconversion boundary that was specified to show equivalence. CONCLUSIONS:
      Although the Ultra-Short regimen has equivalent efficacy to the Thai regimen, it
      also has many practical advantages. Ultra-Short is thus a preferable protocol.

PMID- 16411342
TI  - Test offering, not additional information, may increase HIV testing uptake in a
      knowledgeable population.
AB  - OBJECTIVES: To evaluate patient HIV knowledge and testing experience and assess
      the effect of an HIV informational handout on HIV testing propensity. DESIGN:
      Cross sectional, descriptive techniques were employed to assess demographics, HIV
      knowledge and HIV testing experience. A randomized controlled trial was performed
      to determine if an HIV/AIDS information sheet influenced testing propensity.
      SETTING: Blantyre Adventist Hospital Outpatient Clinic. SUBJECTS: Non-emergency
      patients over 18 years old attending during consulting hours. INTERVENTIONS: All
      subjects answered a questionnaire. For the randomized controlled trial component,
      half received an HIV information handout. MAIN OUTCOME MEASURES: Proportions were
      calculated to evaluate testing experience. Logistic regression was used to assess
      impact of written information and demographics on HIV testing propensity.
      RESULTS: 490 participants were recruited, of whom 57% had never been tested for
      HIV. Of the untested, 88% had never been offered an HIV test. Of those that had
      never been offered a test, 46% desired one. The sample was highly knowledgeable
      about HIV. Reading an information sheet had no impact on HIV knowledge (p=0.736
      to 0.788) or desire for testing (p=0.387). However, age (OR=0.97, 95%CI
      (0.95,0.99)) and gender (OR=1.85, 95%CI (1.06, 3.23)) significantly correlated
      with testing propensity. CONCLUSIONS: A large percentage of patients who have
      never been offered HIV testing desire testing. More frequent HIV test offering by
      clinicians could improve testing rates. Clinician education programmes should be
      developed to increase test offering. Furthermore, written health information in a
      setting of high HIV/AIDS knowledge may not change behaviour. Alternative methods
      should be employed to encourage HIV testing uptake.

PMID- 16411343
TI  - Echocardiographic profile of endomyocardial fibrosis in Tanzania, East Africa.
AB  - OBJECTIVES: To demonstrate and evaluate the usefulness of two dimensional and
      Doppler echocardiography in the diagnosis of endomyocardial fibrosis (EMF) in
      countries with poor resources. Also to evaluate the clinical assessment as a
      predictor of echocardiographically proven EMF. DESIGN: Descriptive hospital based
      study. SETTING: Muhimbili National Hospital, Dar es Salaam, Tanzania. SUBJECTS:
      39 patients (27 male and 12 female, mean age 13.5 years) attending our Cardiac
      Clinic were investigated to determine the extent to which specific features could
      be diagnosed by transthoracic echocardiography. MAIN OUTCOME MEASURES:
      Identifying and characterizing echocardiographic features specific for diagnosing
      EMF non-invasively. RESULTS: Only eight (21%) patients had a correct clinical
      diagnosis, leaving 79% of the patients at risk of being misdiagnosed and hence
      wrongly receiving expensive treatment. The majority of the patients (69.2%)
      presented with signs of elevated systemic venous pressure due to right
      ventricular EMF. CONCLUSION: We have demonstrated that echocardiography remains a
      fundamental investigation in the least developed countries in achieving the
      correct diagnosis.

PMID- 16411344
TI  - Implementation of the prevention of mother-to-child transmission of HIV programme
      in Zimbabwe: achievements and challenges.
AB  - Recent scientific developments have led to feasible and effective interventions
      to reduce the risk of mother to child transmission of HIV. Even in resource poor
      countries, PMTCT programmes are being articulated as a priority in the national
      strategic frameworks. Thus PMTCT programmes are moving from being pilot projects
      to national programmes comprehensively integrated into other reproductive health
      programmes or HIV and AIDS prevention, care and support programmes. In Zimbabwe
      the prevention of mother-to-child transmission (PMTCT) of HIV infection has
      become an important national task. The 2001 national survey of HIV prevalence
      among women attending antenatal care revealed that 29.5% of the women were HIV
      positive. While an effective PMTCT programme using nevirapine can reduce the rate
      of this transmission by 50%, the Zimbabwe PMTCT National Expansion Programme has
      had its share of achievements and challenges since its launch in 2002.

PMID- 16411345
TI  - On specialisation.

PMID- 16411346
TI  - Unlearning.

PMID- 16411347
TI  - Assisted dying: considerations in the continuing debate.

PMID- 16411348
TI  - Going smoke-free: the medical case for clean air in the home, at work and in
      public places.

PMID- 16411349
TI  - Basal cell carcinoma.

PMID- 16411350
TI  - Toxic epidermal necrolysis and Stevens-Johnson syndrome.

PMID- 16411351
TI  - Atopic eczema: a modern epidemic.

PMID- 16411352
TI  - Modern management of psoriasis.

PMID- 16411353
TI  - Acne: current treatment.

PMID- 16411354
TI  - Doctors and managers: building a new relationship.
AB  - There is a long history of problems in the relationship between doctors and
      managers. The reasons for this stem from the values of each group and the effect
      that these have on their views on a number of key aspects of healthcare and its
      delivery. Managers have been seen as the malign embodiment of changes in society
      and the instrument of the wishes of governments, which are often viewed with
      suspicion. High-quality healthcare is dependent on a productive partnership
      between doctors and managers and on doctors being prepared to take leadership
      roles. Both groups have skills and knowledge vital to the other, so each needs to
      recognise the strengths of the other and find ways to develop a productive
      partnership. Clinical work can be improved by the application of management
      techniques, and management would benefit from more clinical leadership.

PMID- 16411355
TI  - The assessment of mental capacity.
AB  - Mental capacity is required for an adult to make autonomous treatment choices.
      This review highlights recent legal and clinical developments in the field. The
      recent English Mental Capacity Act 2005 is described and compared with mental
      health legislation. Some of the difficulties of defining mental capacity are then
      outlined. Recent research regarding mental capacity in general hospital patients
      is summarised. Such research indicates firstly that capacity can reliably be
      assessed; secondly, that among general hospital inpatients, approximately one
      third may lack capacity; and thirdly, that mental incapacity in this setting is
      mainly driven by cognitive impairment caused by delirium or dementia. This is
      contrasted with psychiatric inpatients, where the problem is no more frequent,
      but mainly relates to psychotic illness. The article finishes with some general
      guidance as to how to assess mental capacity in the general hospital.

PMID- 16411356
TI  - The consultant contract: marriage or divorce?
AB  - At the birth of the new millennium Britain's Labour government published a 10
      year plan for modernising the National Health Service (NHS), placing great
      emphasis on new ways of working. As part of this process, and following extensive
      negotiation, general practitioners and hospital consultants were offered new
      contracts in 2003. This process highlighted the issues academic clinicians and
      managers face in dealing with the tensions inherent in delivering the tripartite
      mission of teaching, research and clinical service. Following a retrospective
      review of clinical academic appraisals, this paper considers new strategies for
      strengthening the relationship across the university and NHS interface and how
      this novel and strategic approach might be adopted in future health policy. These
      findings can be helpful for both UK colleagues and for a broader international
      audience by providing a pragmatic approach to increasing collaboration across the
      higher education and health service sectors.

PMID- 16411357
TI  - In celebration of cerebration.

PMID- 16411358
TI  - Digestive endoscopy in five decades.
AB  - The world of gastroenterology changed forever when flexible endoscopes became
      available in the 1960s. Diagnostic and therapeutic techniques proliferated and
      entered the mainstream of medicine, not without some controversy. Success
      resulted in a huge service demand, with the need to train more endoscopists and
      to organise large endoscopy units and teams of staff. The British health service
      struggled with insufficient numbers of consultants, other staff and resources,
      and British endoscopy fell behind that of most other developed countries. This
      situation is now being addressed aggressively, with many local and national
      initiatives aimed at improving access and choice, and at promoting and
      documenting quality. Many more consultants are needed and some should be relieved
      of their internal medicine commitment to focus on their specialist skills. New
      instruments and procedures are stretching the diagnostic boundaries and changing
      the interface with sister disciplines like radiology, surgery and pathology. The
      old distinctions, particularly between gastroenterology and surgery, are
      increasingly irrelevant and unhelpful. The future is bright for gastroenterology
      and for endoscopy, but unpredictable. In this fast-changing world it will be
      essential to remain flexible, with our goals firmly focused on the best interests
      of our patients.

PMID- 16411359
TI  - The impact of weekends on outcome for emergency patients.
AB  - Levels of staffing and access to diagnostics at weekends are recognised to be
      significantly lower than on weekdays. It is unclear if subsequent inpatient
      mortality and readmission rates for acute medical admissions are increased for
      weekend admissions compared to those on a weekday. A large Canadian study
      demonstrated increased weekend mortality but does the Edinburgh healthcare model
      support these findings? This study analysed all hospital admissions in 2001 to
      the Royal Infirmary of Edinburgh for six predetermined diagnoses (total 3,244):
      chronic obstructive pulmonary disease, cerebrovascular accidents, pulmonary
      embolism, pneumonia, collapse and upper gastrointestinal bleed. We compared
      hospital mortality rates, readmission rates and hospital length of stay for
      weekend admissions as compared to those on a weekday. Weekend admission was not
      associated with significantly higher in-hospital mortality, readmission rates or
      increased length of stay compared to the weekday equivalent for any of the six
      conditions. The implementation of an acute medical admissions unit in the Royal
      Infirmary of Edinburgh, with consistent staffing levels and 24-hour access to
      diagnostics for the early phase of critical illness, may have helped address the
      discrepancy in care suggested by previous studies.

PMID- 16411360
TI  - Palliative medicine for the cancer and non-cancer patient.

PMID- 16411361
TI  - Ventilatory failure on acute take.
AB  - The optimal management of acute ventilatory failure lies in a multidisciplinary
      approach focusing on doing simple things correctly, close liaison between
      healthcare professionals and adequate communication with patients and carers. The
      use of NIV support is increasing in a variety of conditions, both inside and
      outside the ICU.

PMID- 16411362
TI  - Identification, management and referral of adults with chronic kidney disease:
      concise guidelines.
AB  - Chronic kidney disease (CKD) is often thought to be a relatively rare condition
      requiring specialist care. However, early CKD is common and referral of all
      patients would completely overwhelm existing specialist services. The purpose of
      this concise guidance is to inform general physicians and general practitioners
      about the identification and management of CKD, and who to refer for specialist
      care.

PMID- 16411363
TI  - End-of-life issues in renal medicine.

PMID- 16411364
TI  - The Royal College of Physicians--ancient and modern.
AB  - The history of the College's first 430 years was covered in three volumes ending
      in 1947. It required an entire fourth volume to cover the next 36 years up to
      1984. During this time the almost incredible changes and advances in medicine
      were accompanied by a metamorphosis in the scale, scope, behaviour and attitude
      of a very traditional College--now housed in one of Denys Lasdun's finest modern
      buildings. Led by a series of remarkable presidents, the College has met its
      challenges with considerable panache. It strongly supported the National Health
      Service at its inception, published ground-breaking reports on smoking and other
      'lifestyle' threats to health, and made constant efforts to improve medical
      standards and defend academic medicine. Its story, as told by Asa Briggs, is
      enough to provide nostalgia for the elderly and much food for thought for the not
      so-old.

PMID- 16411365
TI  - The evolution of restricted hours of duty for resident medical officers in New
      Zealand: a personal view.
AB  - The New Zealand Health Service had to start adapting to significant restrictions
      in junior medical staff's hours of work in the mid-1980s. Some consequences of
      this presage those that will occur in the UK and Europe with the implementation
      of the European Working Time Directive (EWTD). These naturally include continuity
      of patient care, changing responsibility and hours of senior medical and
      administrative staff, some aspects of medical professionalism and training
      issues. Life does, however, go on.

PMID- 16411366
TI  - Mandrake (mandragora root).

PMID- 16411367
TI  - Advance decisions on resuscitation.

PMID- 16411368
TI  - Risk communication.

PMID- 16411369
TI  - Cardiac amyloidosis.

PMID- 16411370
TI  - Conundrum of BMI measurements.

PMID- 16411371
TI  - Prescribing patterns in acutely admitted medical patients: changes over 10 years.

PMID- 16411372
TI  - Everyone a patient? Beware the Commoveamus effect!

PMID- 16411373
TI  - Detection of Chlamydia pneumoniae in atherosclerotic tissue: a comparative study
      of PCR and immunocytochemistry.
AB  - The reported prevalence of Chlamydia pneumoniae in atherosclerotic tissue appears
      to depend on the detection system used. This introduces problems in determining
      the role of C. pneumoniae in atherosclerosis. This study analyses the sensitivity
      and performance of molecular diagnostic methods for the detection of C.
      pneumoniae and polymerase chain reaction (PCR) inhibitors in atheromatous tissue.
      Atherosclerotic tissue taken from 30 coronary endarterectomies, nine coronary
      arteries from explanted hearts, 16 carotid and two femoral endarterectomies are
      studied. Nested PCR (nPCR) assays targeting the PstI restriction fragment, the
      OmpA gene and the CRP operon of the chlamydial genome and immunocytochemistry
      (ICC) are used. Internal controls (IC) are constructed to co-amplify with the
      specific amplicons and identify the presence of inhibitor. The OmpA, PstI and CRP
      operon PCR assays had similar analytical sensitivities. However, the OmpA PCR was
      most affected by PCR inhibitors. Despite this, eight samples (14%) tested
      positive in the OmpA nPCR and no positives were found using the PstI or CRP
      operon nPCRs. Primary isolates of C. pneumoniae obtained from 12 patients with
      acute respiratory infection were positive in all three assays. Of the 48
      specimens available for ICC, 33 (69%) were positive for chlamydial antigens.
      These included samples found positive by PCR. Dilution of samples to eliminate
      PCR inhibitors may have contributed to the discordant ICC and PCR results. The
      OmpA PCR, when used with an IC to identify samples with PCR inhibitors, is a
      reliable tool. However, the sensitivity of the ICC methods justifies their
      continued use.

PMID- 16411374
TI  - Embryopathy in experimental diabetic gestation: assessment of PGE2 level, gene
      expression of cyclooxygenases and apoptosis.
AB  - The causes of, and predisposing conditions for, increased congenital anomalies in
      embryos of experimental diabetic gestation are not fully identified. In the
      present study, some possible factors involved in diabetes-induced embryopathy are
      explored. The concentration of PGE2, the gene expression of cyclooxygenases (COX
      1 and COX-2) and level of apoptosis (measured by caspase-3 activity) are assessed
      during organogenesis in the embryos of streptozotocin-induced diabetic rats. The
      concentrations of PGE2 in the embryos of diabetic rats were lower than controls,
      with the lowest values in malformed embryos and their associated membranes (yolk
      sacs). The pattern of change in PGE2 was similar in the embryos of the control
      and diabetic groups, which showed a steady decline between days 9 and 11 of
      gestation. These changes in PGE2 were accompanied by a small decrease in COX-1
      expression in all embryos and associated membranes during the same gestational
      period. Expression of COX-2, which was below normal in diabetic embryos,
      decreased between days 9 and 11 of gestation in all groups. In the membranes of
      non-malformed embryos, COX-2 expression peaked on day 10 of gestation. It was
      found that there was little or no detectable COX-2 expression in the membranes of
      malformed embryos on day 9 of gestation and although its expression was
      detectable on the following days it was much lower than in the other groups.
      Caspase-3 activity increased substantially between days 9 and 11 of gestation.
      Embryos from the experimentally diabetic group showed higher activity than did
      controls, with the largest increases in the malformed embryos. It would appear
      that COX-2 expression and PGE2 concentration (in both embryo and associated
      membranes) play a significant role in organ formation. The data presented here
      suggest that an unhealthy placenta may be instrumental in the development of
      malformed embryos.

PMID- 16411375
TI  - Antibiotic-associated diarrhoea: an overlooked aetiology?
AB  - Sixty-three faeces samples from hospital in-patients with probable antibiotic
      associated diarrhoea (AAD) are investigated. All samples are examined for routine
      bacterial enteric pathogens, pus cells, red blood cells and parasites. The
      samples are also screened for Clostridium difficile cytotoxin B (CDT), C.
      perfringens enterotoxin and Candida spp. (by microscopy and quantitative
      culture). Faecal samples from two control groups (healthy volunteers and
      community samples from GP patients) are also screened. A possible pathogen was
      found in 71% of AAD cases. Candida spp. overgrowth was the most common (44.4%),
      followed by CDT (34.9%) and Clostridium perfringens enterotoxin (9.5%). There was
      good agreement between the significant Gram films and quantitative Candida spp.
      culture (kappa=0.683). Clinical information revealed the majority of patients
      were on multiple antibiotic regimes, receiving 'high risk' antibiotics. Of
      community samples, 21% were positive for Clostridium perfringens enterotoxin,
      indicating that C. perfringens is a problem in the community, not necessarily
      associated with antibiotic use. The results suggest that quantitative Candida
      spp. culture should be performed on all specimens requesting AAD investigations.

PMID- 16411376
TI  - Characterisation of potentially probiotic vaginal lactobacilli isolated from
      Argentinean women.
AB  - This study aims to evaluate potentially beneficial properties of 20 strains of
      vaginal lactobacilli isolated from women in Tucuman, Argentina, by determining
      acid and hydrogen peroxide production and auto-aggregation ability. The
      microorganisms were characterised genetically by amplified ribosomal 16S-DNA
      restriction analysis (ARDRA). Lactobacillus gasseri and L. rhamnosus were the
      predominant species identified among the 20 vaginal lactobacilli strains. Most
      achieved low pH values after 12 h incubation at 37 degrees C and produced
      hydrogen peroxide in static culture. However, pH decrease and semi-quantitative
      hydrogen peroxide production of most homofermentative lactobacilli were
      significantly higher than those of heterofermentative lactobacilli. Of the 20
      strains studied, only three demonstrated remarkable auto-aggregation patterns.
      Four strains were selected for possible use in a probiotic product for vaginal
      application; however, further in vitro study of other potentially probiotic
      characteristics is required before attempting clinical trials.

PMID- 16411377
TI  - Microbial ecology of the cystic fibrosis lung: does microflora type influence
      microbial loading?
AB  - This study aims to examine the association between the numbers of culturable
      microbial species forming the microflora of the lung in patients with cystic
      fibrosis (CF) and microbial loading (i.e., type[s] versus numbers). Additionally,
      it examines qualitative combinations of the microflora present in a large adult
      CF centre (n=138) in order to ascertain ecological relationships between the taxa
      present. The culturable microflora of sputum from 34 adults patients with CF are
      enumerated using a spread plate technique on non-selective agar, and the
      microflora identified phenotypically employing the API 20NE scheme.
      Microbiological examination of the 34 adult patients demonstrated that their
      sputum contained between one and three taxa, with a mean cell density of 8.25 +/-
      0.85 log colony-forming units (cfu)/g sputum and a range of 5.91-9.74 log cfu/g
      sputum. Most colonising patterns demonstrated only Gram-negative infection
      (22/34), followed by a mixed Gram-positive/Gram-negative infection pattern
      (10/34). Only 2/34 patients had a single Gram-positive infection. Most patients
      (53%) were colonised by only one organism, with 38% of patients colonised by two
      organisms, and the remainder (4%) colonised with three organisms. There was no
      statistical difference (P>0.05) between microbial cell density and the number of
      taxa present (i.e., the greater number of taxa present in sputum did not produce
      a higher cell density). However, there was a significantly higher cell density
      (log 0.59 cfu/g sputum) noted for those patients who had only Gram-negative
      infection, compared to those who had a mixed Gram-negative/Gram-positive
      infection pattern (P=0.02). Relatively little is known about the ecological
      interactions that exist between the microflora in the CF lung. Further work is
      required to explore these interactions in order to aid understanding of the
      succession and dominance of Gram-negatives in chronic chest infections.
      Ultimately, a greater understanding of such interactions may allow the
      opportunity to manipulate the ecology of the lung to control otherwise
      problematic pathogens

PMID- 16411378
TI  - Evaluation of three commercial agar preparations for the presumptive
      identification of significant urinary isolates.
AB  - Three commercially available pre-poured chromogenic preparations--chromogenic
      urinary tract infection (UTI) medium (chromogenic UTI, Oxoid), CHROMagar
      Orientation (Becton Dickinson) and CPS ID2 (bioMerieux)--are evaluated in
      comparison to routine urine microbiology using cysteine lactose electrolyte
      deficient (CLED) medium and conventional methods of identification and
      susceptibility testing by Vitek 1 for the majority of isolates. Most isolates
      were Escherichia coli, and a chromogenic medium has been shown to be a reliable,
      rapid and more economic medium on which to presumptively identify these organisms
      due to the substrates the strain utilises in the plate and the chromogen
      subsequently produced. However, the opacity of chromogenic UTI made the medium
      difficult to inoculate and read, although the colours were clear and strong.
      Although there was no statistical difference between CHROMagar Orientation and
      CPS ID2, the colours observed on the former were stronger. This meant that colony
      counting was possible at significant concentrations of 10(4) and 10(5) colony
      forming units (cfu)/mL and it may be easier to detect mixtures that would
      indicate contamination. Chromogenic media are richer than CLED and a number of
      Lactobacillus spp. (normally regarded as normal flora) grew on this medium. These
      were not considered to be significant.

PMID- 16411379
TI  - What can cytologists learn from 25 years of investigations in visual search?
AB  - This review aims to provide an insight into the nature and mechanisms of the
      visual screening of cytological preparations and to discuss the implications for
      current practice. Visual perception in cytology is under-researched and deserves
      further investigation. Fundamental issues to be addressed include the mechanisms
      of visual scanning of cytological preparations and the factors affecting search
      performance. Answers to these questions will have wide reaching impact on issues
      such as liquid-based technology, automated screening, training, quality
      assurance, recruitment and selection of staff, and medico-legal problems.

PMID- 16411380
TI  - Trichomonas vaginalis: paradigm of a successful sexually transmitted organism.
AB  - Trichomonas vaginalis (TV) is one of the most successful protozoan pathogens and
      one of the most common sexually transmitted organism in females, yet it is also
      one of the most poorly investigated. By producing a wide array of glycosidases
      and cysteine proteinase enzymes, the organism can easily adapt to the
      environment, harvesting host proteins and DNA for metabolism. With the ability to
      cause lesions, vaginitis and acute inflammatory disease of the genital mucosa, TV
      acts as a potential catalyst in the acquisition of secondary infections including
      human immunodeficiency virus (HIV) and human papillomavirus (HPV), the organism
      responsible for the pathogenesis of cervical cancer. Treatment of TV infection is
      relatively easy and could dramatically reduce the transmission of HIV in areas
      where TV is endemic.

PMID- 16411381
TI  - Epithelium, heal thyself!

PMID- 16411382
TI  - Leukocyte-platelet aggregates: new particles reflecting and effecting
      cardiovascular disease.

PMID- 16411383
TI  - Structure, function and biology of tissue factor pathway inhibitor-2.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is a 32 kDa matrix-associated Kunitz
      type serine proteinase inhibitor consisting of a short amino-terminal
      region,three tandem Kunitz-type domains and a positively charged carboxy-terminal
      tail. Human TFPI-2, previously designated as placental protein 5, inhibits a
      broad spectrum of serine proteinases almost exclusively through its first Kunitz
      type domain, and is thought to play an important role in the regulation of
      extracellular matrix digestion and remodeling. In this context, reduced synthesis
      of TFPI-2 has been related to numerous pathophysiological processes such as
      inflammation, angiogenesis, atherosclerosis, retinal degeneration and tumor
      growth/metastasis. In this review, we document current information regarding the
      expression of TFPI-2 by various tissues, its inhibitory activity and proteinase
      specificity in-vitro, and discuss possible physiological roles for this inhibitor
      based on in-vivo studies.

PMID- 16411384
TI  - Molecular analysis of the heavy chain variable region genes of human hybridoma
      clones specific for coagulation factor VIII.
AB  - HemophiliaA is a X-linked hematologic disorder characterized by undetectable or
      low amounts of functional coagulation factor VIII (FVIII). Replacement therapy
      induces FVIII neutralizing antibody (Ab) (inhibitor) in a proportion of patients
      which makes further treatment of these patients ineffective and costly. To
      envisage mechanisms underlying inhibitor development, seven hybridoma clones
      specific for FVIII were generated from two hemophilia A patients with high titer
      of inhibitor. Specificity and isotype of the monoclonal antibodies (mAbs) were
      determined by ELISA. Immunoglobulin (Ig) variable region heavy (VH) chain gene
      family usage was identified by RT-PCR using VH1-6 specific primers. Nucleotide
      sequences of the VH gene of FVIII specific clones were determined and aligned to
      the most homologous germ line genes in the GenBank. Analysis of the expressed VH
      genes by RT-PCR revealed that the hybridomas utilized either the VH1 (71%) or the
      VH3 (29%) gene family. Three VH domains were encoded by V1-69 (DP-10),V1-2 (DP
      8), and V1-8 (DP-15) genes and two by V1-18 (DP-14) gene, all from the VH1 gene
      family. Of theVH3-gene family expressing clones, one belonged to V3-66 (DP-86)
      and the other one to V3-21 (DP-77) germline genes. The CDR3 length was found to
      be highly different amongst these clones ranging from 11 to 22 amino acid
      residues. These data suggest that FVIII-specific Abs preferentially use VH gene
      segments derived from VH1 gene family. Diversity of the expressed VH genes and
      their CDR3 length implies that different epitopes are recognized by these mAbs.

PMID- 16411385
TI  - An important role for the activation peptide domain in controlling factor IX
      levels in the blood of haemophilia B mice.
AB  - The factors responsible for the removal of injected factor IX (fIX) from the
      blood of individuals with haemophilia B are only partly understood, and may
      include binding to endothelial or subendothelial sites, passive extravasation
      related to size or charge, or interactions requiring fIX activation. To
      investigate these issues, we have produced and characterised recombinant fIX
      proteins with amino acid changes: delta155-177, an internal deletion which
      removes most of the activation peptide while retaining the activation cleavage
      sites; S365A, which inactivates the serine protease activity of fIXa; and K5A,
      previously shown to eliminate fIX binding of endothelial/subendothelial collagen
      IV. All proteins were expressed in stably transfected HEK 293 cells, purified by
      immunoaffinity chromatography, and compared to the wild type HEK 293-derived
      protein (fIX (WT)). Mutant fIX proteins K5A and delta155-177 exhibited 72 and
      202% of the specific activity of fIX (WT), respectively; S365A was without
      activity. Following intravenous injection in haemophilia B (fIX knockout) mice,
      recoveries did not differ for fIX (WT) and delta155-177, but were higher for K5A
      and S365A. The terminal catabolic half-life of delta155-177, alone among the
      mutants, was increased, by 45% versus fIX (WT). Nine hours post-injection, the
      observed areas under the clearance curve (AUCs) of delta155-177 and K5, but not
      S365A, were elevated 2-fold. delta155-177 was equally effective as fIX (WT) in
      reducing blood loss following tail vein transection in haemophilia B mice. Our
      results suggest that deletion of the multiple sites of fIX post-translational
      modification found within the activation peptide eliminated important fIX
      clearance motifs.

PMID- 16411386
TI  - The effects of supra-normal protein C levels on markers of coagulation,
      fibrinolysis and inflammation in a human model of endotoxemia.
AB  - The protein C pathway serves as a modulating system with both anti-inflammatory
      and anticoagulant properties and is intimately involved in the pathophysiology of
      inflammation and sepsis. Treatment with recombinant human activated protein C
      (rhAPC) can reduce the mortality of severe sepsis. We investigated whether an
      elevation of plasma protein C levels to supra-normal levels by infusion of a
      protein C zymogen concentrate has an effect on coagulation, protein C activation
      or inflammation in a human endotoxemia model. Eleven healthy male volunteers were
      enrolled in a double-blind, placebo-controlled two-way cross-over trial. Ten
      minutes after infusion of 2ng/kg endotoxin each volunteer received either placebo
      or a plasma-derived protein C zymogen concentrate (Ceprotin, Baxter) (150 U/kg as
      a slow bolus infusion followed by 30 U/kg/h continuous infusion until 4 hours
      after LPS-infusion). Protein C antigen and activity increased 4- to 5-fold after
      infusion of the concentrate. APC was generated during endotoxin-induced
      inflammation in the placebo (1.6 fold increase) and the protein C period (4.0
      fold increase). The increase of APC levels correlated with the TNF-alpha and IL-6
      release in both periods (r = 0.65-0.68; p < 0.05) and paralleled the protein C
      antigen and activity levels in the period with supranormal protein C levels.
      Supra normal protein C levels resulted in slightly, although non-significant,
      lower tissue factor mRNA expression and thrombin generation (TAT, F1+2). Systemic
      inflammation (TNF-alpha, IL-6) was not influenced by protein C zymogen
      concentrate administration. Infusion of protein C zymogen was safe and no adverse
      effects occurred. The increase of protein C levels several fold above the normal
      range resulted in a proportional increase of the APC levels, but had no major
      anticoagulant, anti-inflammatory or profibrinolytic effects. Low grade
      endotoxemia itself induces significant protein C activation, which correlates
      with the TNF release.

PMID- 16411387
TI  - Pharmacodynamic markers in the early clinical assessment of otamixaban, a direct
      factor Xa inhibitor.
AB  - This manuscript reports the assessment of pharmacodynamic (PD) markers of anti
      coagulation in the first-in-man study with the novel direct Factor Xa (FXa)
      inhibitor, otamixaban, with a brief description of safety and pharmacokinetic
      (PK) findings. The study comprised ten consecutive parallel groups of healthy
      male subjects (6 active, 2 placebo per group). Eight groups received escalating
      intravenous doses of otamixaban as 6-hour infusions (1.7 to 183 microg/kg/h) and
      two groups received a bolus dose (30 or 120 microg/kg) with a 6-hour infusion (60
      or 140 microg/ kg/h, respectively). PD markers included anti-FXa activity and
      clotting time measurements, i.e. activated Thromboplastin Time (aPTT),
      Prothrombin Time (PT), Heptest Clotting Time (HCT), and Russell's Viper Venom
      induced clotting Time (RVVT). In addition, Endogenous Thrombin Potential (ETP)
      was assessed in the bolus-plus-infusion dose groups. Otamixaban was well
      tolerated. Otamixaban plasma concentrations increased with escalating dose, were
      maximal at the end-of-infusion (C(eoi)), and decreased rapidly as the infusion
      was stopped. Anti-FXa activity coincided with otamixaban plasma concentrations
      and clotting time measurements followed the same pattern. Maximal changes from
      baseline at C(eoi) were 1.9 +/- 0.2 for aPTT, 2.0 +/- 0.2 for PT, 5.1 +/- 0.6 for
      HCT, and 4.5 +/- 1.2 for RVVT. Otamixaban inhibited thrombin generation (24%
      decrease in ETP) and a delay in thrombin generation was noticed in vitro at high
      concentrations.

PMID- 16411388
TI  - Dose-finding and pharmacokinetics of therapeutic doses of tinzaparin in pediatric
      patients with thromboembolic events.
AB  - In children, there is an increasing off-label use of low molecular weight heparin
      (LMWH). However, there is an absence of information on dosing and
      pharmacokinetics of LMWH over all age groups. The objectives of the current study
      were to determine i) the once daily dose required to achieve anti-Xa levels of
      0.5-1.0 IU/mL, ii) the pharmacokinetics and iii) preliminary safety data using
      tinzaparin. The study took the form of a single centre open-label Phase II study
      performed in 35 children requiring anticoagulation for treatment of
      thromboembolism. Age groups studied were: 0- < 2 months; 2 months- < 1 year; 1- <
      5 years; 5- < 10 years; 10-16 years. Both population pharmacokinetic analysis
      using nonlinear mixed-effect modeling techniques and model-independent
      pharmacokinetic methods were employed. Results showed a relationship of age and
      dose requirements, clearance, time to peak anti-Xa level and volume of
      distribution. Younger children required an increased dose, cleared tinzaparin
      more rapidly, had anti-Xa levels peak earlier and had an increased volume of
      distribution. Younger children were more likely to be below target range than
      older children,with up to 75% of children < 1 year being below the target anti-Xa
      level. Four recurrences and one major bleed occurred. In conclusion, there is an
      inverse relationship of age on dose requirements related to volume of
      distribution, clearance and time to peak anti-Xa. Children < 5 years likely
      require dose adjustment samples to be drawn 2-3 hours post injection. Infants
      require anti-Xa levels to be monitored at least twice monthly.

PMID- 16411389
TI  - Molecular mechanisms of antithrombin deficiency in two Chinese families. One
      novel and one recurrent point mutation in the antithrombin gene causing venous
      thrombosis.
AB  - We investigated the molecular mechanisms responsible for type I congenital
      antithrombin (AT) deficiency in two unrelated Chinese pedigrees manifesting
      multiple site venous thrombosis. Phenotype analysis showed both probands had
      almost 50% of normal AT levels. Direct sequencing of amplified DNA revealed 2757C
      > T in proband 1 and 13328G > A in proband 2, predicting a heterozygous Thr98Ile
      (T981) and Ala404Thr (A404T), respectively. No proband had 20210A allele or
      factor V Leiden mutation. Transient expression of complementary DNA coding for
      the mutations in COS-7 cells showed impaired secretion of the mutant molecules.
      Real-time quantitative PCR indicated that the mutant AT mRNA was transcribed at a
      similar or even higher level as that of wild-type (wt). Pulse-chase labeling
      studies suggested both AT variants did not accumulate, but degraded
      intracellularly. Immunohistochemical staining of the transfected cells revealed
      that CHO cells expressing the AT-198 mutant were stained diffusely without
      perinuclear enhancement and cells expressing AT-T404 mutant mainly in the whole
      cytoplasm with weaker perinuclear enhancement. We conclude that the impaired
      secretion of the mutant AT molecules, due to intracellular degradation, is the
      molecular pathogenesis of AT deficiency caused by T981 and A404T mutation for the
      two families, respectively.

PMID- 16411390
TI  - Continuous infusion of recombinant factor VIIa for surgery in patients with
      deficiency of factor VII.
AB  - The administration of recombinant activated factor VII (rFVIIa) by continuous
      infusion has provided a safe and convenient alternative to bolus injections in
      haemophiliacs with inhibitors, but it has only been reported in a single case
      with congenital factor VII (FVII) deficiency. The results of 12 consecutive
      surgical procedures in 7 patients with congenital FVII deficiency are reported
      here. rFVIIa was always given in continuous infusion,aiming at plasma FVII
      activity of 0.5 IU/mL. Treatment was given for 2 to 7 days with a mean total dose
      of 7.8 mg rFVIIa. Blood loss was as expected from the different types of
      procedures and the only thromboembolic complication was a superficial
      thrombophlebitis at the infusion site. This mode of substitution was therefore
      safe, effective and well tolerated.

PMID- 16411391
TI  - Intermittent pneumatic compression and deep vein thrombosis prevention. A meta
      analysis in postoperative patients.
AB  - Our objective was to overview the effectiveness of intermittent pneumatic
      compression (IPC) devices to prevent deep vein thrombosis (DVT) in postoperative
      patients, using meta-analysis methodology. We searched the Medline, metaRegister
      of Controlled Trials, and Cochrane database for studies published between 1970
      and October 2004. Our inclusion criteria were: 1) randomized controlled trial of
      IPC versus no prophylaxis, 2) at least 20 patients per group, 3) at least one
      diagnostic DVT imaging test in all patients, and 4) clinical follow-up for at
      least the duration of hospitalization. A total of 2,270 patients were included in
      15 eligible studies: 1,125 and 1,145 in the IPC and no prophylaxis group,
      respectively. The included studies formed a total of 16 treatment groups and were
      conducted in orthopedic (5), general surgical (4),oncologic (3), neurosurgical
      (3) and urologic (1) patient populations. In comparison to no prophylaxis, IPC
      devices reduced the risk of DVT by 60% (relative risk 0.40, 95% CI 0.29 - 0.56; p
      < 0.001). Contemporary randomized trials should be undertaken to test the utility
      of IPC in hospitalized medical patients as well as combined pharmacological plus
      IPC prophylaxis in both medical and surgical patients.

PMID- 16411392
TI  - Is factor V Leiden a risk factor for thrombotic microangiopathies without severe
      ADAMTS 13 deficiency?
AB  - About 60% of patients diagnosed with acute thrombotic thrombocytopenic purpura
      (TTP) display a severe ADAMTS13 deficiency. Recently, Raife et al. concluded from
      a small case series, that factor V Leiden (FVL) might constitute a risk factor
      for acute thrombotic microangiopathy (TMA) without severe ADAMTS13 deficiency.
      Therefore, we determined ADAMTS13 activity and FVL carrier-ship in 256
      consecutive patients presenting with various forms of acute TMA, including
      patients diagnosed with TTP or hemolytic-uremic syndrome (HUS). The overall
      prevalence of FVL was 8.2% (6.25% among patients diagnosed with TTP, and 9% among
      those with HUS) concordant with the FVL prevalence reported in Europe. FVL was
      present in 9.9% of patients with ADAMTS 13 activity < 10% and in 9.7% of those
      with normal ADAMTS13 activity (> 50%). We conclude that FVL is not more prevalent
      in TMA patients without as compared to those with severe ADAMTS13 deficiency. The
      prevalence of FVL carriers in certain HUS subgroups (HUS with ADAMTS 13 activity
      > 50%) reaching 12.3% suggests that a contributory role of FVL in the
      pathogenesis of defined forms of HUS needs further study.

PMID- 16411393
TI  - Inverse relationship between plasminogen activator inhibitor-I activity and
      adiponectin in overweight and obese women. Interrelationship with visceral
      adipose tissue, insulin resistance, HDL-chol and inflammation.
AB  - Adipose tissue is an active endocrine organ secreting different adipokines such
      as plasminogen activator inhibitor-1 (PAI-1) and adiponectin, among many others.
      In this study, we investigated the association between PAI-1 activity and serum
      adiponectin levels in a group of 444 overweight and obese women and assessed the
      interrelationship with visceral adipose tissue (VAT; CT-scan L4-L5), insulin
      resistance (HOMA-IR), HDL cholesterol (HDL-chol) and inflammation (hs-CRP). PAI-1
      was inversely related to adiponectin (r = -0.25, p < 0.001; adjusted for age and
      BMI). After adjustment for age, VAT, HOMA-IR and hs-CRP, the relationship
      remained significant (r = -0.15; p = 0.001), but disappeared after additional
      adjustment for HDL-chol (r = -0.09; p = 0.067). Subjects were divided in two
      groups according to the median levels of adiponectin or PAI-1 levels. PAI-1
      activity (19.1 +/- 11.4 vs. 15.8 +/- 8.6 AU/ml; p = 0.003) and adiponectin levels
      (9.8 +/- 4.6 vs. 8.4 +/- 4.0 microg/ml; p < 0.001) were significantly higher in
      the low adiponectin/PAI-1 groups. The difference in PAI-1 remained significant
      after adjustment for age and BMI (p = 0.001), became borderline significant after
      adjustment for age and VAT (p = 0.052), and disappeared after adjustment for age
      and HOMA-IR (p = 0.116) or age and HDL-chol (p = 0.443). The difference in
      adiponectin levels remained significant after adjustment for age, VAT, HOMA-IR
      and hs-CRP (p = 0.006), but disappeared after additional adjustment for HDL-chol
      (p = 0.089). Further analyses suggest a contribution of HOMA-IR and/or HDL-chol
      in the relationship between PAI-1 and adiponectin. HDL-chol was found to be the
      only factor independently determining both factors. In conclusion, in overweight
      and obese women, PAI-1 activity was inversely related to serum adiponectin,
      independent of visceral adipose tissue.

PMID- 16411394
TI  - Point-of-care testing of the international normalized ratio in patients with
      antiphospholipid antibodies.
AB  - Antiphospholipid antibodies can influence the results of clotting tests in a
      subset of patients, which can be a major obstacle in monitoring warfarin. The aim
      was to determine if point-of-care testing of the International Normalized Ratio
      (INR) is influenced by antiphospholipid antibodies. We compared 59 patients
      receiving warfarin for a diagnosis of antiphospholipid antibody syndrome (APS) to
      49 patients receiving warfarin for atrial fibrillation to evaluate the
      consistency between INR results obtained by different methods. INR results
      obtained by finger stick (capillary whole-blood) and venipuncture (non-citrated
      and citrated whole-blood) were compared with our laboratory plasma-based
      prothrombin time assay. Five patients (8%) with APS and both elevated anti
      beta2glycoprotein I levels and positive lupus anticoagulants had non-measurable
      ProTime INR results and generally higher Hemochron Signature INR results than the
      plasma-based method, but the corresponding chromogenic factor X results were not
      supratherapeutic. For the remaining patients, differences between the plasma
      based INR and the point-of-care INR results ranged from 0.2 +/- 0.2 to 0.4 +/-
      0.3. The differences were similar for patients with APS and atrial fibrillation
      for all INR comparisons with the exception of the plasma-based method compared
      with the ProTime, which showed a mean absolute difference of 0.4 +/- 0.3 for APS
      patients and of 0.2 +/- 0.2 for atrial fibrillation patients (p = 0.02). In a
      subset ofAPS patients, the ProTime system will not yield an INR result and the
      HEMochron Signature (citrate and non-citrate whole-blood) INR results will
      exhibit elevated INR results. For this subset of APS patients, we suggest using
      an alternative method to monitor warfarin.

PMID- 16411395
TI  - Platelet adhesion: structural and functional diversity of short dystrophin and
      utrophins in the formation of dystrophin-associated-protein complexes related to
      actin dynamics.
AB  - Platelets are dynamic cell fragments that modify their shape during activation.
      Utrophin and dystrophins are minor actin-binding proteins present in muscle and
      non-muscle cytoskeleton. In the present study, we characterised the pattern of
      Dp71 isoforms and utrophin gene products by immunoblot in human platelets. Two
      new dystrophin isoforms were found, Dp71f and Dp71 d, as well as the Up71 isoform
      and the dystrophin-associated proteins, alpha and beta -dystrobrevins.
      Distribution of Dp71d/Dp71delta110m, Up400/Up71 and dystrophin-associated
      proteins in relation to the actin cytoskeleton was evaluated by confocal
      microscopy in both resting and platelets adhered on glass. Formation of two
      dystrophin-associated protein complexes (Dp71d/Dp71delta110m approximately DAPC
      and Up400/Up71 approximately DAPC) was demonstrated by co-immunoprecipitation and
      their distribution in relation to the actin cytoskeleton was characterised during
      platelet adhesion. The Dp71d/Dp71delta100m approximately DAPC is maintained
      mainly at the granulomere and is associated with dynamic structures during
      activation by adhesion to thrombin-coated surfaces. Participation of both
      Dp71d/Dp71delta110m approximately DAPC and Up400/Up71 approximately DAPC in the
      biological roles of the platelets is discussed.

PMID- 16411396
TI  - The influence of the haematocrit on primary haemostasis in vitro.
AB  - Primary haemostasis consists of platelet adhesion to subendothelial collagen,
      their activation and aggregation and finally the formation of a platelet plug.
      Erythrocytes are involved in this process because they flow in the center of the
      vessel and push platelets towards the site of action on the vessel wall and
      enhance shear forces, which activate platelets. In the platelet function analyzer
      PFA-100 (Dade Behring, Dudingen, Switzerland), the in vivo situation is simulated
      in vitro with blood being aspirated at high shear rates (5000s(-1)) through a
      capillary into a membrane pore with a diameter of 150 microm coated with type I
      collagen and either epinephrine or adenosine diphosphate. Aggregating platelets
      plug the pore and stop the flow, which is measured as the closure time. We
      analysed the influence of erythrocytes on platelet function analyzer measurements
      by systematic variation of the haematocrit (20, 30, 40, and 50%) at constant
      platelet counts of 289 +/- 61 x 10(3)/microl plasma, or 152 +/- 30 x 10(3)/microl
      blood, 96 +/- 9 x 10(3)/microl blood and 54 +/- 5 x 10(3)/microl blood,
      respectively. An inverse correlation was found between haematocrit and closure
      time under all circumstances. A decrease of the platelet count by 50 x
      10(3)/microl could be compensated for by a 10% increase in haematocrit. The
      haematocrit must, therefore, be taken into consideration for the correct
      interpretation of PFA-100 measurements. Our data also provide a
      pathophysiological rationale to reduce the risk of bleeding in patients with
      thrombocytopenia and anaemia by normalizing the haematocrit with erythrocyte
      transfusions.

PMID- 16411397
TI  - Chorioamnionitis is associated with increased CD40L expression on cord blood
      platelets.
AB  - Chorioamnionitis (CA) is a severe infection responsible not only for premature
      birth but also for many severe neonatal diseases. The aim of the present study
      was to investigate the expression of CD40L and P-selectin on platelets and the
      plasma levels of their soluble forms in the umbilical cord blood in infants with
      documented chorioamnionitis. Umbilical cord blood samples were obtained from 10
      healthy term newborns, 10 non-infected preterm infants, 10 preterm infants with
      premature rupture of membranes and 9 preterm infants with clinical and
      histological CA. The expression of CD40L and P-selectin on platelets was analyzed
      by flow cytometry. Soluble P-selectin (sCD62P), soluble CD40L (sCD40L) and
      interleukine-6 (IL-6) were measured in plasma by ELISA assays. Neonates with CA
      had significantly higher percentages of platelets expressing CD40L in basal
      conditions (5.3 +/- 2.9% vs. 1.6 +/- 0.7% and in non-infected preterm infants p <
      0.05), while the percentages of P-selectin positive platelets were similar among
      all groups. In contrast, the level of sP-selectin was higher in infants with CA
      (222 +/- 128 ng/ml vs. 104 +/- 71 ng/ml in non-infected preterm infants, p <
      0.05) but no differences were found in the levels of sCD40L. As expected, the
      levels of IL-6, a pro-inflammatory cytokine were significantly higher in samples
      obtained from preterm neonates whose mothers had also elevated inflammatory
      parameters. Our observations suggest that platelets are involved in the complex
      inflammatory pathogenesis of CA. Neither P-selectin expression on cord blood
      platelets nor plasma sP-selectin or sCD40L were suitable platelet markers in CA,
      whereas CD40L was significantly elevated in histologically proven CA.

PMID- 16411398
TI  - Functional heterogeneity of alloantibodies against the human platelet antigen
      (HPA)-1a.
AB  - The integrin alphaIIbbeta is the major fibrinogen receptor on the platelet
      membrane and plays a crucial role for platelet aggregation. The beta3-subunit
      carries the human platelet alloantigen (HPA)-1a, which is the main target for
      alloantibodies (alloabs) responsible for foetal and neonatal alloimmune
      thrombocytopenia (FNAIT) and post-transfusion purpura (PTP). Whereas PTP is
      almost invariably associated with severe bleeding, the clinical presentation of
      FNAIT ranges from mild thrombocytopenia to severe haemorrhagic diathesis.
      However, this clinical heterogeneity is not fully understood as it is not
      explained solely by the variability of the platelet count. Here, we examined the
      ability of HPA-1a alloabs from mothers with FNAIT (n = 43) and PTP patients (n =
      8) to inhibit cell adhesion to fibrinogen and asked if this inhibition was
      correlated with the heterogeneity of the clinical picture. Stably transfected
      cells expressing HPA-1a (beta3-Leu33) and -1b (beta3-Pro33) isoforms were
      incubated with sera containing HPA-1a alloabs and were allowed to adhere to
      immobilised fibrinogen. The inhibitory activity was measured as percentage of
      cell adhesion in the presence of patient sera versus normal AB serum. Only two
      FNAIT sera specifically inhibited the adhesion of HPA-1a, but not HPA-1b cells.
      Two other FNAIT sera blocked the adhesion of HPA-1a as well as HPA-1b cells.
      Interestingly, all four neonates with inhibitory HPA-1a alloabs (9% of all sera)
      suffered severe bleeding. In comparison, the majority of PTP sera (75%) inhibited
      cell binding to fibrinogen, four PTP sera selectively inhibited the adhesion of
      HPA-1a cells whilst 2 sera impaired the binding of both allotypes. Our
      observations indicate that 1) HPA-1a alloabs are heterogeneous in their ability
      to interfere with fibrinogen binding, and 2) inhibition of the alphaIIbbeta3
      fibrinogen receptor by HPA-1a alloabs may contribute to pronounced bleeding in
      patients with alloimmune thrombocytopenia.

PMID- 16411399
TI  - Neutrophil P-selectin-glycoprotein-ligand-1 binding to platelet P-selectin
      enhances metalloproteinase 2 secretion and platelet-neutrophil aggregation.
AB  - Platelets and neutrophils constitute a high source of metalloproteinases (MMPs),
      and their interactions via P-selectin and P-selectin-glycoprotein-ligand-1 (PSGL
      1) are involved in thrombosis, vascular remodelling, and restenosis. We
      investigated the impact of these interactions on platelet MMP-2 secretion and
      function in platelet and neutrophil aggregation. The secretion of MMP-2 from
      human platelets was significantly increased three-fold after thrombin activation,
      and enhanced two-fold in the presence of neutrophils. Neutrophil supernatant had
      no effect on platelet MMP-2 secretion. While no MMP-2 was detected in the
      supernatant of neutrophils, a high amount of MMP-9 was released by neutrophils,
      and remained unchanged upon thrombin activation or in the presence of platelets.
      Platelet P-selectin, which increased significantly after activation, triggered
      platelet binding to neutrophils that was completely inhibited by P-selectin or
      PSGL-1 antagonists, and was reduced by 50% with a GPIIb/ IIIa antagonist. P
      selectin or PSGL-1 antagonism abolished the enhanced secretion of platelet MMP-2
      in the presence of neutrophils and reduced platelet-neutrophil aggregation.
      Platelet activation and binding to neutrophils enhance the secretion of platelet
      MMP-2 via an adhesive interaction between P-selectin and PSGL-1, which contribute
      to increase platelet-neutrophil aggregation.

PMID- 16411400
TI  - Discrepancy between tissue factor activity and tissue factor expression in
      endotoxin-induced monocytes is associated with apoptosis and necrosis.
AB  - Tissue factor (TF), the main initiator of blood coagulation, contributes to the
      manifestation of disseminated intravascular coagulation following septic shock in
      meningococcal infection. Since a direct relationship between disease severity and
      lipopolysaccharide (LPS) concentration in the circulation has been shown, we
      hypothesized that the procoagulant and cytotoxic effects of endotoxin also in
      vitro were related to its concentration. In vitro studies, however, have
      frequently used much higher LPS concentrations than those observed in clinical
      samples. Using elutriation-purified human monocytes, we observed that LPS up to
      1000 ng/ml exerted a concentration-dependent increase in TF activity (tenase
      activity, fibrin formation in plasma). Although there was a dose-dependent
      increase in TF activity, there was not a concomitant increase in TF expression at
      LPS concentrations above 1 ng/ml (flow cytometry, Western blotting, TF mRNA).
      Flow cytometry revealed that this discrepancy between TF activity and TF
      expression at endotoxin concentrations above 1 ng/ml, coincided with an LPS dose
      dependent increase in cell surface phosphatidylserine (PS), considered to promote
      coagulation. The increased PS expression was associated with an increased number
      of 7-AAD-positive cells indicating cell death. We conclude that enhancement of
      monocyte procoagulant activity in vitro by high concentrations of LPS may result
      from increased PS exposure due to apoptosis and necrosis. Therefore, the LPS
      concentrations used to examine monocyte procoagulant activity in vitro, should be
      carefully chosen.

PMID- 16411401
TI  - The effect of long-term, low-dose tranexamic acid treatment on platelet
      dysfunction and haemoglobin levels in haemodialysis patients.
AB  - Some previous studies suggest that activation of the fibrinolytic system may
      induce platelet dysfunction in haemodialysis patients. Accordingly, inhibition of
      fibrinolysis may improve platelet dysfunction, and speculatively increase
      haemoglobin levels. We tested this hypothesis. The study group comprised 22
      patients (14 male, 8 female, median age 62), who had been on maintenance
      haemodialysis for more than one year. Patients were treated for three months with
      low-dose tranexamic acid (TXA), a potent anti-fibrinolytic agent. The dosages of
      erythropoietin and the haemodialysis procedure were not changed significantly
      during the study. We primarily followed platelet function (by in vitro closure
      time test) and haemoglobin values. Patients were divided into those with
      substantially prolonged (N = 9) and those with slightly delayed or normal (N =
      13) in vitro closure time. Treatment with TXA resulted in a significant
      improvement of platelet function and increased levels of haemoglobin in the first
      group, and no changes in either platelet function or haemoglobin values in the
      second group. TXA in the dosage used was biologically active, since a significant
      decrease in plasminogen and D-dimer were found in both groups. No significant
      changes in other fibrinolytic parameters or von Willebrand factor were found. No
      complications in terms of arterial or venous thrombosis were observed. Our pilot
      study suggests that long-term, low-dose TXA treatment of haemodialysis patients
      with substantially prolonged in vitro closure time results in a significant
      improvement of platelet dysfunction and a significant increase in haemoglobin
      values. These new, promising results merit further investigation in larger
      studies.

PMID- 16411402
TI  - Fractalkine receptor polymorphisms V2491 and T280M as genetic risk factors for
      restenosis.
AB  - The chemokine fractalkine (FKN) recruits leukocytes into lesions of the arterial
      wall, which may lead to restenosis after stenting. FKN also regulates
      proliferation of smooth muscle cells, another mechanism pivotal to neointimal
      thickening. We assessed the hypothesis that functionally important polymorphisms
      of the FKN receptor CX3CR1 influence restenosis after coronary stenting. Three
      hundred and sixty-five patients undergoing coronary stenting were genotyped for
      the CX3CR1 polymorphisms V2491 and T280M. Restenosis occurred in 25% of patients,
      and recurrent (> 1) restenosis at the target lesion in 8%. The allele 1249 was
      associated with an increased risk of restenosis (adjusted odds ratio 2.4, 95%
      confidence interval: 1.3-4.2, P = 0.003) and recurrent restenosis (odds ratio
      2.7, 95% confidence interval: 1.3-5.9, P = 0.011). Particularly, patients with
      1249 lacking the allele M280 were at an elevated risk of restenosis (P = 0.006)
      and, accordingly, the haplotype containing 1249 but not M280 was more frequent in
      patients with restenosis (P = 0.001). In conclusion, the CX3CR1 1249 allele is
      associated with an increased risk of restenosis while the CX3CR1 M280 allele
      might counteract the harmful influence of 1249. These findings show the
      importance of the chemokine FKN and genetic variations of its receptor for
      restenosis after coronary stenting. Recognition of these inherited risk modifiers
      may help to individualize treatment of coronary stenosis.

PMID- 16411403
TI  - Urokinase plasminogen activator released by alveolar epithelial cells modulates
      alveolar epithelial repair in vitro.
AB  - Intra-alveolar fibrin is formed following lung injury and inflammation and may
      contribute to the development of pulmonary fibrosis. Fibrin turnover is altered
      in patients with pulmonary fibrosis, resulting in intra-alveolar fibrin
      accumulation, mainly due to decreased fibrinolysis. Alveolar type II epithelial
      cells (AEC) repair the injured alveolar epithelium by migrating over the
      provisional fibrin matrix. We hypothesized that repairing alveolar epithelial
      cells modulate the underlying fibrin matrix by release of fibrinolytic activity,
      and that the degree of fibrinolysis modulates alveolar epithelial repair on
      fibrin. To test this hypothesis we studied alveolar epithelial wound repair in
      vitro using a modified epithelial wound repair model with human A549 alveolar
      epithelial cells cultured on a fibrin matrix. In presence of the inflammatory
      cytokine interleukin-1beta, wounds increase by 800% in 24 hours mainly due to
      detachment of the cells, whereas in serum-free medium wound areas decreases by
      22.4 +/- 5.2% (p < 0.01). Increased levels of D-dimer, FDP and uPA in the cell
      supernatant of IL-1beta-stimulated A549 epithelial cells indicate activation of
      fibrinolysis by activation of the plasmin system. In presence of low
      concentrations of fibrinolysis inhibitors, including specific blocking anti-uPA
      antibodies, alveolar epithelial repair in vitro was improved, whereas in presence
      of high concentrations of fibrinolysis inhibitors, a decrease was observed mainly
      due to decreased spreading and migration of cells. These findings suggest the
      existence of a fibrinolytic optimum at which alveolar epithelial repair in vitro
      is most efficient. In conclusion, uPA released by AEC alters alveolar epithelial
      repair in vitro by modulating the underlying fibrin matrix.

PMID- 16411404
TI  - Molecular weight determines the frequency of delayed type hypersensitivity
      reactions to heparin and synthetic oligosaccharides.
AB  - Eczematous lesions, resulting from type IV sensitizations are well-known and
      relatively frequent cutaneous adverse effects of s.c. heparin therapy. If
      anticoagulation is further required intravenous heparin, heparinoids or lepirudin
      may be used as a substitute. However, these alternatives are not optimal in terms
      of practicability and/or safety-profiles. As molecular weight of different
      heparin preparations has repetitively been implied to determine the frequency of
      sensitization, we hypothesized, that due to its low molecular weight the
      pentasaccharide fondaparinux may provide a practicable and safe anticoagulant
      therapy in patients with delayed type hypersensitivity reactions (DTH) to heparin
      and other oligosaccharides. To test this concept, patients referred for diagnosis
      of cutaneous reactions after s.c. anticoagulant treatment underwent a series of
      in vivo skin allergy- and challenge-tests with unfractionated heparin, a series
      of low molecular weight heparins (nadroparin, dalteparin, tinzaparin, enoxaparin
      and certoparin), the heparinoid danaparoid and the synthetic pentasaccharide
      fondaparinux. In total, data from twelve patients was evaluated. In accordance
      with previously published data, we report a high crossreactivity among heparins
      and heparinoids. In contrast--and in support of our initial hypothesis-
      sensitization towards the synthetic pentasaccharide fondaparinux was rarely
      observed. Plotting the cumulative incidence against the determined molecular
      weight of the individual anticoagulant preparations, shows that molecular weight
      generally is a key determinant of sensitization towards heparins and other
      oligosaccharides (r2 = 0.842, p = 0.009). Hence, fondaparinux may be used as a
      therapeutic alternative in patients with cutaneous DTH relations towards heparin
      and other polysaccharides.

PMID- 16411405
TI  - Presence of endothelial progenitor cells, distinct from mature endothelial cells,
      within human CD146+ blood cells.
AB  - CD146 is an adhesion molecule present on endothelial cells throughout the
      vascular tree. CD146 is also expressed by circulating endothelial cells (CECs)
      widely considered to be mature endothelial cells detached from injured vessels.
      The discovery of circulating endothelial progenitor cells (EPCs) originating from
      bone marrow prompted us to investigate whether CD146 circulating cells could also
      contains EPCs. We tested this hypothesis using an approach combining elimination
      of CECs by an adhesion step, followed by immunomagnetic sorting of remaining
      CD146+ cells from the non adherent fraction of cord blood mononuclear cells. When
      cultured under endothelial-promoting conditions, these cells differentiated as
      late outgrowth endothelial colonies: they grew as a cobblestone monolayer, were
      uniformly positive for endothelial markers and did not express leukocyte
      antigens. They highly proliferated and were expanded in long-term culture without
      alterations of their phenotypic and functional properties (Dil-ac-LDL uptake,
      wound repair, capillary-like network formation, and TNFalpha response). Moreover,
      these cells colonized a Matrigel plug in immunodeficient mice (NOD/SCID).
      Finally, using 4-color flow cytometry analysis of purified CD34+ cells, we
      clearly discriminated, CD146+ EPCs (CD146+ CD34+ CD45+ CD133+ or CD117+), and
      CD146+ CECs (CD146+ CD34+, CD45- CD133- or CD117-), both in cord and adult
      peripheral blood.The relative proportions of the two CD146+ subsets varied in
      patients with myocardial infarction as compared to healthy subjects. Our study
      establishes that, beside CECs, CD146+ circulating cells contain a subpopulation
      of EPCs with potential use in proangiogenic therapy. In addition, the dual
      measurement of CD146+ CECs and CD146+ EPCs offers a promising tool for monitoring
      vascular injury/regeneration processes in clinical situations.

PMID- 16411406
TI  - The first assessment of soluble CD146 in women with unexplained pregnancy loss. A
      new insight?
AB  - The mechanisms responsible for pregnancy loss have not all been elucidated. CD146
      is a cell adhesion molecule involved in the control of both endothelium integrity
      and intermediate trophoblast invasiveness, two potential key features in the
      pathogenesis of pregnancy loss. As CD146 is detectable as a soluble form in the
      plasma (sCD146), we investigated sCD146 plasma levels in women with a history of
      pregnancy loss. We conducted a paired case-control study to compare sCD146 plasma
      levels in 100 women with unexplained pregnancy losses (2 or more consecutive
      losses at or before 21 weeks of gestation, or at least one later loss) and in 100
      age-matched control women (no pregnancy loss and at least one living child). The
      sCD146 concentrations were determined at least 2 months after the last
      obstetrical event. Patients and controls were comparable regarding thrombophilia.
      Among the patients, 83 women experienced early pregnancy losses (average of 3
      losses, mean gestation of 6.6 weeks) and 22 women suffered at least one late
      pregnancy loss. We found significantly higher sCD146 plasma levels in the 100
      patients compared to age matched control women (p < 0.001). The sCD146 plasma
      levels did not correlate with the number of pregnancy losses nor with the mean
      gestation time. Alterations in sCD 146 plasma levels could be related to
      endothelial dysfunction associated to defective endovascular trophoblast
      invasiveness. Additional studies should explore whether sCD146 assessment could
      provide diagnostic and prognostic information with a view to screening and thus
      managing women with unexplained pregnancy loss.

PMID- 16411407
TI  - Homocysteine rapidly increases matrix metalloproteinase-2 expression and activity
      in cultured human vascular smooth muscle cells. Role of phosphatidyl inositol 3
      kinase and mitogen activated protein kinase pathways.
AB  - In this study we aimed to test the hypothesis that in human vascular smooth
      muscle cells (VSMC) homocysteine influences synthesis and release of matrix
      metalloproteinase-2 (MMP-2), which is deeply involved in vascular remodeling and
      atherosclerotic plaque instabilization. Experiments were carried out in cultured
      human VSMC exposed to 50-500 micromol/l homocysteine after a 24-hour culture with
      MEM containing 0.1% BSA. Both in supernatants and cell lysates we evaluated MMP-2
      activity (gelatin zimography), MMP-2 andTIMP-2 protein synthesis (Western
      immunoblotting). Homocysteine effects were investigated also after cell exposure
      to i) specific MEK inhibitor PD98059 (30 micromol/l) to evaluate the involvement
      of Mitogen-Activated Protein Kinase (MAPK) and ii) specific phosphatidylinositol
      3-kinase (P13-K) inhibitor LY294002 (100 micromol/l) to evaluate the involvement
      of P13-K pathway. Gelatin zimography evidenced that MMP-2 activity is increased
      both in conditioned media and in cell lysates starting from 8-hour incubation
      with 100 micromol/l homocysteine. Western blot analysis evidenced increased MMP-2
      levels in both conditioned media and cell lysates. Cell exposure to PD98059 and
      LY294002 prevented homocysteine effects on MMP-2 synthesis. Homocysteine, at
      concentrations associated with increased risk of cardiovascular events, increases
      MMP-2 activity, synthesis and secretion in VSMC through a mechanism involving the
      activation of MAPK and P13-K pathways. These data suggest that homocysteine is
      directly involved in mechanisms leading to remodelling and instabilization of
      atherosclerotic plaques.

PMID- 16411408
TI  - Synergistic association between hypercholesterolemia and the C46T factor XII
      polymorphism for developing premature myocardial infarction.
AB  - Factor XII (FXII) plays a key role in both coagulation and fibrinolysis, thus its
      role in thrombotic processes is uncertain. Both genetic and environmental factors
      determine FXII plasma levels. A common C46T polymorphism in the Kozak region of
      F12 gene disturbs the translation of the protein leading to a significant
      reduction of FXII levels although its clinical significance is conflictive. We
      studied the F12 C46T polymorphism in 281 patients who had suffered from an acute
      myocardial infarction (MI) before 45-year-old and 550 control subjects from the
      same area. Serum levels of cholesterol, HDL, LDL, triglycerides and C reactive
      protein (CRP) were assayed in the MI group. The 46T allele slightly increased the
      risk to suffer from premature MI (OR: 1.64; 95% CI: 1.14-2.37; p = 0.008).
      Moreover, patients carrying the 46T allele showed increased levels of CRP (p =
      0.002). Interestingly, we found that the simultaneous presence of the 46T allele
      and hypercholesterolemia increases the risk to develop premature MI 2.26 times.
      The F12 C46T polymorphism, associated with a reduction of plasma FXII levels,
      seems to play a deleterious effect, predisposing the development of premature MI,
      especially in hypercholesterolemic patients. This effect could be associated with
      an increased pro-inflammatory state, as the 46T allele associates with high
      levels of CRP.

PMID- 16411409
TI  - Anti-thrombotic action of clopidogrel and P1(A1/A2) polymorphism of beta3
      integrin in patients with coronary artery disease not being treated with aspirin.
AB  - Individual variability in response to clopidogrel is known but its mechanism is
      poorly understood. We examined the relationship between glycoprotein IIIa
      polymorphism P1(A1/A2) and anti-thrombotic actions of clopidogrel. Clopidogrel
      (75 mg/d; 2 weeks) was administered to 48 normolipemic patients with coronary
      artery disease. Bleeding time, thrombin generation at the site of microvascular
      injury, platelet function under high shear, using PFA-100 with ADP cartridge, and
      platelet surface activation markers (P-selectin and fibrinogen binding sites on
      GPIIb/IIIa complex detected by PAC-1 antibody), were studied both before and
      after clopidogrel treatment. Both unstimulated and low-dose (0.02 microM and 1
      microM) in vitro ADP-stimulated platelets were examined. GP IIIa polymorphism was
      assessed by polymerase chain reaction and restriction fragment length
      polymorphism analysis. We identified 32 P1(A1/A1) homozygotes, 15 P1(A1/A2
      heterozygotes and one P1(A2/A2) homozygote. Clopidogrel significantly prolonged
      bleeding time in all subjects, but this effect was greater in P1(A2 carriers (p <
      0.01). Furthermore, clopidogrel only depressed thrombin generation at the site of
      microvascular injury (p < 0.01) in P1(A2) patients and prolonged closure time
      measured in vitro by PFA-100 (p < 0.05). At baseline spontaneous expression of
      PAC-1 and P-selectin was higher in P1(A2) subjects as compared to P1(A1)
      homozygotes (p < 0.05 for both antigens). Clopidogrel lowered the expression of
      both markers affecting more P1(A2) carriers, so that the difference in binding
      PAC-1 antibody between platelets from P1(A1) and P1(A2) carriers disappeared,
      while the difference in P-selectin expression slightly diminished. Anti
      thrombotic effects of clopidogrel are more pronounced in CAD patients carrying
      the P1(A2) allele than in P1(A1) homozygotes.

PMID- 16411410
TI  - Endurance training reduces circulating asymmetric dimethylarginine and
      myeloperoxidase levels in persons at risk of coronary events.
AB  - Asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and paraoxonase 1
      (PON1) are directly involved in the pathogenesis of atherosclerosis by modulation
      of oxidative stress and/or NO bioavailability. We aimed to assess whether
      endurance exercise which is known to be cardioprotective could beneficially
      affect these novel risk markers. Thirty-two subjects (31-68 yrs, 56% males) with
      elevated cardiovascular risk including ten patients with coronary artery disease
      volunteered for a supervised 12-week endurance training (196 +/- 15 min/week).
      Their fitness evaluated by 2 km test runs improved significantly after training
      (pre: 17.3 +/- 0.8 vs. post: 15.7 +/- 0.9 min, p < 0.001). ADMA (pre: 0.94 +/-
      0.03 vs. post: 0.75 +/- 0.04 micromol l(-1)) and MPO (pre: 296.8 +/- 22.2
      vs.post: 185.7 +/- 19.5 ng ml(-1)) serum levels decreased significantly by 17.6
      +/- 4.6% and 28.5 +/- 7.5%, respectively, after training (both p < 0.001). Their
      down-regulation was inversely correlated (ADMA: r = -0.609, p < 0.001, MPO: r = 
      0.437, p = 0.014) with the up-regulation of plasma cGMP levels (Cyclic-guanosine
      3',5'-monophosphate; pre: 1.6 +/- 0.12 vs. post: 2.21 +/- 0.2 micromol ml(-1), p
      = 0.001) reflecting NO production. PON1 activity towards phenylacetate was not
      significantly influenced by training (pre: 133 +/- 6 vs. post: 130 +/- 5 micromol
      ml(-1) min(-1), p = 0.375). In a matched inactive control group (n = 16) ADMA,
      MPO, cGMP levels and PON1 activity did not change over time. ADMA, MPO and cGMP
      changes were significantly different between participants and controls (all p <
      0.05). Regular endurance exercise was successful in reducing the circulating
      levels of two promising cardiovascular risk markers, ADMA and MPO, in persons
      prone to cardiac events. These changes may result in numerous antiatherosclerotic
      effects such as improvement of NO bioavailability, reduction of oxidative stress
      and lipid peroxidation.

PMID- 16411411
TI  - D-dimer, P-selectin, and microparticles: novel markers to predict deep venous
      thrombosis. A pilot study.
AB  - Current plasma markers for diagnosis of deep venous thrombosis (DVT) allow for
      exclusion of the diagnosis, but lack adequate specificity to establish the
      diagnosis. Thus, a prospective study was performed to determine the sensitivity
      and specificity of plasma assays for D-dimer, soluble P-selectin (P-selectin),
      and total microparticles in patients with documented DVT by duplex ultrasound.
      Three groups of individuals were examined: 30 normals; 22 positive for DVT on
      duplex ultrasound (Group 2); and 21 symptomatic, but negative on duplex
      ultrasound for DVT (Group 3). Group 1 individuals had D-dimer values of 1.53 +/-
      0.12 mg/l and P-selectin values of 0.34 +/- 0.05 ng/mg total protein. Group 2 vs.
      Group 3 individuals had D-dimer values of 7.57 +/- 2.03 vs. 3.19 +/- 0.79 mg/l, p
      = 0.02; P-selectin values of 0.98 +/- 0.11 vs. 0.55 +/- 0.08 ng/mg total protein,
      p < 0.01; and micro-particle values of 129 +/- 17% vs. 99 +/- 12% of control, p =
      ns. Using a logistic regression model with dichotomous variables, we determined a
      sensitivity of 73%, specificity of 81%, and accuracy of 77% when combining D
      dimer, soluble P-selectin, and total microparticles to differentiate Group 2 from
      Group 3 patients. Logistic regression using continuous variables yielded similar
      results (p = 0.05). This study demonstrates that plasma markers for DVT can be
      developed and achieve moderate sensitivity and specificity in diagnosing DVT.
      However for clinical applicability, the sensitivity/specificity will need to be
      improved. These studies also suggest the importance of soluble P-selectin in
      assessing DVT in humans.

PMID- 16411412
TI  - Platelet integrin alpha2 I-domain specific antibodies produced via domain
      specific DNA vaccination combined with variable gene phage display.
AB  - Antibodies are a powerful tool for structure/function studies of platelet
      proteins. However, classic immunisation frequently elicits antibody responses
      against domains of minor functional interest. Robust strategies to generate
      antibodies against defined domains would be of significant interest in post
      genome research. In this study, we report a new strategy using a combination of
      DNA vaccination and V gene phage display that allows the rapid generation of
      domain specific single-chain Fv antibodies (scFvs). This system was validated
      using the I-domain of alpha2 integrin as a model. The alpha2beta1 integrin, which
      is expressed on many cell types, is the dominant collagen attachment receptor on
      platelets, functioning in close interplay with the collagen signalling receptor
      glycoprotein VI. A novel set of I-domain specific antibodies was obtained by a
      DNA vaccination/V gene repertoire cloning approach. Mice were first immunised
      with a DNA vaccine in which the alpha2 I-domain is expressed as a fusion protein
      with fragment C of tetanus toxoid (FrC-TT). Then the heavy and kappa light chain
      variable gene repertoires were rescued from immune splenocytes using antibody
      phage display. A total of four alpha2 I-domain specific scFvs were isolated by
      selection on recombinant I-domain or native platelet alpha2beta1 integrin.
      Characterisation of the scFvs indicated that they recognised distinct epitopes
      that had profound differences in accessibility between native and recombinant I
      domain. Our data suggest DNA immunisation and phage display represent versatile
      alternatives to protein immunisation and hybridoma-fusion techniques for the
      isolation of recombinant antibody reagents. This approach will be particularly
      useful for the generation of domain or splice-variant specific antibodies that
      recognise native protein.

PMID- 16411413
TI  - Angiographic documentation of the efficacy of recombinant activated factor VII
      (NovoSeven) to control diffuse bleeding in major trauma.

PMID- 16411414
TI  - Pregnancy-associated deep vein thrombosis in a double homozygous carrier of
      factor V Leiden and prothrombin G20210A.

PMID- 16411415
TI  - Primary antiphospholipid syndrome and factor V Leiden mutation in a young patient
      with non-bacterial thrombotic endocarditis and transient ischemic stroke.

PMID- 16411416
TI  - Splenic thrombosis in three patients with moderate hyperhomocysteinemia, low
      folate and the C677T variant of the methylenetetrahydrofolate reductase (MTHFR)
      gene.

PMID- 16411417
TI  - Expression of bone-regulating factors osteoprotegerin (OPG) and receptor
      activator of NF-kappaB ligand (RANKL) in heterotopic vascular ossification.

PMID- 16411418
TI  - Prothrombin overload causes thromboembolic complications in prothrombin complex
      concentrates: in vitro and in vivo evidence.

PMID- 16411419
TI  - Protein S gene polymorphisms Pro626 and nt2698--no correlation to free protein S
      levels or protein S activities.

PMID- 16411420
TI  - Hypofibrinolysis during induction treatment of multiple myeloma may increase the
      risk of venous thrombosis.

PMID- 16411421
TI  - Ambulatory therapy of patients with free-floating proximal deep vein thrombosis
      is safe.

PMID- 16411423
TI  - Bone conduction hearing on the teeth of the lower jaw.
AB  - Bone conduction stimulation of the teeth of the lower jaw initiates auditory
      sensations. However the lower jaw is only loosely coupled to the skull by the
      temporo-mandibular joint. Therefore the 'classical' bone conduction pathway
      involving skull vibration transmission entirely along bone to the temporal
      petrous bone requires further consideration. Bone conduction hearing thresholds
      to stimulation at the forehead and at the teeth of the upper and lower jaw were
      determined in human subjects. Thresholds on the teeth were better than those on
      the forehead and there was no difference between the thresholds measured
      following stimulation of the upper and lower teeth. Experiments in guinea-pigs
      provided evidence that vibration of the teeth leads to transmission of the audio
      frequency vibrations by means of soft tissue, through skull foramina, into the
      skull cavity (brain and CSF) and from there by fluid channels directly into inner
      ear fluids, exciting the cochlea.

PMID- 16411422
TI  - Genetics of deafness: recent advances and clinical implications.
AB  - Genetic research into the causes of deafness has advanced considerably in the
      last years. Progress has been made in both discovering loci and cloning genes
      associated with syndromic and non-syndromic hearing loss. To date, close to 75
      loci have been identified and 29 genes have been cloned for non-syndromic
      deafness. The proteins these genes encode range from transcription factors to
      molecular motors to ion channels. We review the recent discoveries and discuss
      the impact of this research.

PMID- 16411425
TI  - Auditory backward masking in normal hearing children.
AB  - Backward masking (BM) is an auditory phenomenon in which the threshold of an
      auditory signal is elevated due to the presence of another signal (masker) that
      follows it. Models related to central auditory temporal processes, such as the
      'temporal window' model, have been suggested to explain this phenomenon. If this
      assumption is correct then BM thresholds are expected to improve as a function of
      age. Electrophysiological data suggest that the central auditory system undergoes
      maturation in the first two decades of life. Empirical data on the development of
      BM with age are limited. Therefore, the goals of the present study were to study
      the effect of age on the performance of backward masking in normal developing
      children and to determine the age at which children reach adult-like performance.
      Subjects were 30 normal developing children divided into three groups according
      to age: 7, 9 and 11 years old. Stimuli consisted of a 1000 Hz pure tone and a
      bandpass masker (600-1400 Hz). Three BM threshold estimates were obtained for
      each subject using a three-alternative forced-choice adaptive procedure. The data
      show a trend for improvement in backward-masking thresholds with increasing age.
      Specifically, 7 and 9 year-old children performed significantly poorer than those
      reported for adults, whereas 11 year-old children reached adult-like performance.
      These data contribute to the small body of literature on backward masking in
      normal developing children. They are in keeping with what is known regarding the
      age of physiological maturation of the auditory system and have important
      clinical implications in the assessment of children with suspected temporal
      processing deficits.

PMID- 16411424
TI  - A comparison between vocal reaction time and word recognition measures of
      children with APD and age-matched peers using auditory word discrimination test.
AB  - The purpose of this study was to investigate the possibility of improving speech
      recognition testing sensitivity in children with auditory processing disorders
      (APD) by incorporating response time measures. A group of children identified in
      a clinical setting as having APD was compared to an age-matched peer group using
      a vocal reaction time (VRT) format. The participants were between the ages of 5.5
      and 15 years. All children were presented spoken monosyllabic words of the
      clinical Hebrew speech discrimination test. Statistically significant differences
      were found, with means in the APD children reflecting slower performance than
      that of their peers. The two groups did not differ in their performance accuracy.
      These data show that combining response time measures with percent correct scores
      improved test sensitivity. Such an approach may hold promise for future clinical
      applications in the assessment of APD.

PMID- 16411426
TI  - Underlying mechanism for categorical perception: tone-onset time and voice-onset
      time evidence of Hebrew voicing.
AB  - The nature of the mechanism responsible for the categorical labeling of stimuli
      is not clear. One hypothesis suggests that categorization is limited by the
      'natural sensitivities' of the auditory system. The alternative hypothesis
      suggests that categorization is mediated by a special speech mode and is
      influenced by how speech is produced. The present study attempts to provide some
      insight into this dilemma by evaluating categorical perception (CP) in speech and
      non-speech stimuli and across languages. Specifically, the goals of the present
      study were (1) to compare phonetic boundaries of Hebrew voicing to categorical
      boundaries (CB) of a two-tone complex which varies in the relative timing of the
      two tones (TOT) [TOT stimuli are considered be the non-speech analog to voice
      onset time (VOT)], and (2) to re-establish the CB values of non-speech analog to
      voicing in American-English speakers using the same TOT continua as the Hebrew
      speakers and to compare them to CB of Hebrew-speaking subjects. Our assumption
      was that if CP is mediated by basic auditory sensitivity then we expect similar
      CB for speech and non-speech stimuli and no effect of language on CB. If,
      however, a special speech code determines CP, then phonetic boundaries are
      expected to be different from CB of non-speech stimuli and across languages. Of
      particular interest is the special case of Hebrew whose voice-voiceless
      distinction in production is very different from that in English. Twelve Hebrew
      speaking adults and 12 American-English speaking adults participated in this
      study. Stimuli consisted of (a) a two-tone complex continuum that varied in the
      relative onset time of the lower tone from a lead of -100 ms to a lag of +50 ms
      in 10 ms steps, and (b) a /ba-pa/ continuum which varied in VOT values similar to
      (a). Subjects identified TOT stimuli as belonging to one of three categories:
      leading, simultaneous, or lagging. VOT stimuli were labeled as /ba/ or /pa/.
      Results show (a) different phonetic boundary for Hebrew voicing compared to
      published data on English voicing, (b) different category boundaries for speech
      and non-speech stimuli in Hebrew, (c) a phonetic boundary for Hebrew voicing that
      does not align with the VOT values of production, and (d) very similar CB for TOT
      stimuli in Hebrew- and American-English-speaking subjects. The data support the
      influence of both general auditory abilities and unique speech processes on
      categorical perception of speech.

PMID- 16411427
TI  - Time course of auditory cortex activation during speech processing.
AB  - The purpose of the studies summarized in this report was to determine the time
      course of auditory cortex involvement in speech and language processing in the
      context of auditory object formation. Forty-one subjects took part in the three
      studies summarized in this report. In all three studies, subjects performed a
      choice-reaction task that required their pressing an appropriate button in
      response to auditory stimuli (speech/non-speech, good/worse fused phonemes,
      first/second language words) presented through earphones. Event-related
      potentials (ERPs) were recorded during performance of the task from 21 scalp
      electrodes, in addition to peri-ocular electrodes for monitoring eye movements.
      Current densities within the gray matter of the brain were estimated using the
      LORETA (low resolution electromagnetic tomography) method. In general, except for
      some periods, processing phonetic and linguistic information was associated with
      elevated activity in the left auditory cortex. Peaks in auditory cortex
      activation corresponded in time to scalp recorded peaks in the latencies of P1
      and up to as late as P3. The adjacent posterior temporal areas showed a similar
      temporal pattern of activation, but tended to be less lateralized to the left, or
      even biased toward right hemisphere predominance, depending on the stimulus,
      particularly in the later time frames. The results indicate that the auditory
      cortex is engaged in auditory processing from its early stages and as long as a
      few hundreds of msec, even after cessation of the stimulus, defining sounds as
      distinct auditory objects and differentiating speech from non-speech material,
      relying on acoustic cues. Hemispheric dominance fluctuates to include activity in
      the 'non-dominant' hemisphere depending on stimulus type and stage of processing.

PMID- 16411428
TI  - [Human Genome Project and its impact on biology and medicine].

PMID- 16411429
TI  - [Database annotating the human genome].

PMID- 16411430
TI  - [Human transcriptome].

PMID- 16411431
TI  - [Human proteome].

PMID- 16411432
TI  - [Comparative studies on human and chimpanzee genomes].

PMID- 16411433
TI  - [Human viewed from genome as a primate species].

PMID- 16411434
TI  - [Search for type 2 diabetes susceptibility genes].

PMID- 16411435
TI  - [Advanced genomic analyses for hypertension].

PMID- 16411436
TI  - [Genome analysis on autoimmune thyroid disease].

PMID- 16411437
TI  - [Genetic approach to identify susceptibility genes for allergic diseases].

PMID- 16411438
TI  - [Analyses of genetic factors in osteoporosis].

PMID- 16411439
TI  - [Application of DNA microarray-based high throughput gene analysis system for
      molecular diagnosis].

PMID- 16411440
TI  - [Molecular genetics of Alzheimer's disease].

PMID- 16411441
TI  - [Gene expression analysis of acute myeloid leukemia to understand leukemogenic
      pathways associated with differentiation inhibition].

PMID- 16411442
TI  - [Development and application of bacterial artificial chromosome (BAC)-based CGH
      array].

PMID- 16411443
TI  - [Genome-wide analyses of gene expression and function in C. elegans].

PMID- 16411444
TI  - [Comprehensive analysis of genome function in Drosophila].

PMID- 16411445
TI  - [Recent advances in developmental genomics of the ascidian Ciona intestinalis].

PMID- 16411446
TI  - [Medaka draft genome: toward an understanding of vertebrate development and
      evolution].

PMID- 16411447
TI  - [Complete rice genome sequence information: the key for elucidation of Rosetta
      stones of other cereal genome].

PMID- 16411448
TI  - [Looking for molecular basis of speciation in cichlids].

PMID- 16411449
TI  - [Exploration of constitution-related genes by mouse genome polymorphisms].

PMID- 16411450
TI  - [Systematic genome function analysis of model bacteria].

PMID- 16411451
TI  - [Metabolomics: system for genome interacting with environments through chemical
      substances].

PMID- 16411452
TI  - [Acquisition and evolution of virulence gene systems in pathogenic bacteria].

PMID- 16411453
TI  - [Mechanism of origin and evolution of eukaryote on basis of genome analysis of a
      red alga Cyanidioschyzon merolae].

PMID- 16411454
TI  - [Genetic network controlling cell differentiation in Dictyostelium].

PMID- 16411455
TI  - [Genomics of plant-microbe interactions].

PMID- 16411457
TI  - [Computational analyses of biomedical literature for understanding living
      organisms].

PMID- 16411456
TI  - [Recent progress and perspective of bacteria genome sequencing].

PMID- 16411458
TI  - [Why biology needs to study what biology knows?].

PMID- 16411461
TI  - [Dynamic pathway modeling language: CSML].

PMID- 16411460
TI  - [Trends in interactomics].

PMID- 16411459
TI  - [Introduction to genome assembler].

PMID- 16411462
TI  - [System understanding of ERK signal network: mechanisms for detecting temporal
      rate and final concentration of growth factors].

PMID- 16411463
TI  - [Prediction and analyses of functional RNAs].

PMID- 16411465
TI  - [Beware of scale-freeness].

PMID- 16411464
TI  - [Analysis of structures and dynamics of biological information networks].

PMID- 16411466
TI  - [Genome square: will direct conversations between scientists and the public
      become a new method for the communication of science in the society?].

PMID- 16411467
TI  - [Human genome research and bioethics].

PMID- 16411469
TI  - "Carrying ointments and even pills!" Medicines in the work of Henry Street
      Settlement visiting nurses, 1893-1944.

PMID- 16411470
TI  - Splendid scope for public service: leading the London County Council Nursing
      Service, 1929-1948.

PMID- 16411471
TI  - The Third Reich in the pages of the American Journal of Nursing, 1932-1950.

PMID- 16411472
TI  - Industry and autonomy in early occupational health nursing: the welfare officers
      of the Lancashire cotton mills in the mid-twentieth century.

PMID- 16411473
TI  - "Officer. Nurse. Woman." Army Nurse Corps recruitment for the Vietnam War.

PMID- 16411474
TI  - Upper social strata women in nursing in Turkey.

PMID- 16411476
TI  - Maria Stromberger: a nurse in the resistance in Auschwitz.

PMID- 16411475
TI  - Venny Snellman, Finnish nurses, and Rockefeller Foundation support, 1929-1956.

PMID- 16411477
TI  - Mildred Tuttle: private initiative and public response in nursing education after
      World War II.

PMID- 16411478
TI  - Frances U. Reiter and the Graduate School of Nursing at the New York Medical
      College, 1960-1973.

PMID- 16411479
TI  - Textual analysis as a method for historians of nursing.

PMID- 16411480
TI  - Attention-memory interactions in scene perception.
AB  - The perception of natural scenes relies on the integration of pre-existing
      knowledge with the immediate results of attentional processing, and what can be
      remembered from a scene depends in turn on how that scene is perceived and
      understood. However, there are conflicting results in the literature as to
      whether people are more likely to remember those objects that are consistent with
      the scene or those that are not. Moreover, whether any discrepancy between the
      likelihood of remembering schema-consistent or schema-inconsistent objects should
      be attributed to the schematic effects on attention or on memory remains unclear.
      To address this issue, the current study attempted to directly manipulate
      attention allocation by requiring participants to look at (i) schema-consistent
      objects, (ii) schema-inconsistent objects, or (iii) to share attention equally
      across both. Regardless of the differential allocation of attention or object
      fixation, schema-consistent objects were better recalled whereas recognition was
      independent of schema-consistency, but depended on task instruction. These
      results suggest that attention is important both for remembering low-level object
      properties, and information whose retrieval is not supported by the currently
      active schema. Specific knowledge of the scenes being viewed can result in the
      recall of non-fixated objects, but without such knowledge attention is required
      to encode sufficient detail for subsequent recognition. Our results demonstrate
      therefore that attention is not critical for the retrieval of objects that are
      consistent with a scene's schematic content.

PMID- 16411481
TI  - Stereoscopic acuity and observation distance.
AB  - The amount of depth perceived from a fixed pattern of horizontal disparities
      varies with viewing distance. We investigated whether thresholds for
      discriminating stereoscopic corrugations at a range of spatial frequencies were
      also affected by viewing distance or whether they were determined solely by the
      angular disparity in the stimulus prior to scaling. Although thresholds were
      found to be determined primarily by disparity over a broad range of viewing
      distances, they were on average a factor of two higher at the shortest viewing
      distance (28.5 cm) than at larger viewing distances (57 to 450 cm). We found the
      same pattern of results when subjects' accommodation was arranged to be the same
      at all viewing distances. The change in thresholds at close distances is in the
      direction expected if subjects' performance is limited by a minimum perceived
      depth.

PMID- 16411482
TI  - Effects of 'local' clutter on human target detection.
AB  - In theory, properties of clutter can be defined globally or locally. However, in
      the literature, the distinction between local and global clutter is arbitrary,
      where the standard approach of setting the local domain to twice the expected
      target size, in applying local clutter metrics, is adopted without any
      justification. This paper addresses this problem and considers the implications
      for the application of clutter metrics. It was found that the size of the local
      clutter region around a target has a strong effect on the probability of
      detection of that target and that this is affected by regions much larger than
      twice the target size. It was also discovered that this effect was much stronger
      for targets subtending less than 0.8 degrees of visual angle than for larger
      targets. In the case of the former, the fall-off in human visual performance with
      clutter region size was approximately quadratic, compared to a slight linear fall
      off for larger targets. A simple model is presented explaining these phenomena,
      indicating that the auto-covariance function characterising the clutter is the
      main determinant of the size of the region of local clutter.

PMID- 16411483
TI  - Saccadic target selection as a function of time.
AB  - Recent evidence indicates that stimulus-driven and goal-directed control of
      visual selection operate independently and in different time windows (van Zoest
      et al., 2004). The present study further investigates how eye movements are
      affected by stimulus-driven and goal-directed control. Observers were presented
      with search displays consisting of one target, multiple non-targets and one
      distractor element. The task of observers was to make a fast eye movement to a
      target immediately following the offset of a central fixation point, an event
      that either co-occurred with or soon followed the presentation of the search
      display. Distractor saliency and target-distractor similarity were independently
      manipulated. The results demonstrated that the effect of distractor saliency was
      transient and only present for the fastest eye movements, whereas the effect of
      target-distractor similarity was sustained and present in all but the fastest eye
      movements. The results support an independent timing account of visual selection.

PMID- 16411484
TI  - Synergy of features enables detection of texture defined figures.
AB  - Traditional theories of early visual processing suggest that elementary visual
      features are handled in parallel by independent neural pathways. We studied the
      interaction of orientation and spatial frequency in the discrimination of Gabor
      random fields. Target textures differed from reference textures either in mean
      feature value, showing an edge-like transition between both textures (edge
      defined), or in the degree of feature homogeneity with smooth transitions (region
      defined). Irrespective of the kind of texture definition, we found strong cue
      summation for targets defined by both cues simultaneously, provided two
      conditions were fulfilled. First, they were barely discriminable when defined by
      one cue alone. Second, the target elements formed a closed 2D surface. Only
      marginal cue summation was observed when target elements were heterogeneously
      distributed in a predefined area, lacking a clear 2D shape. Our findings indicate
      that feature synergy enables figure-ground segregation when the information from
      independent feature-specific pathways is insufficient for solving this task.

PMID- 16411485
TI  - Promoting best practice in the procurement of wound products.

PMID- 16411486
TI  - Understanding the principles of wound management.

PMID- 16411487
TI  - The role of the tissue viability clinical nurse specialist.

PMID- 16411488
TI  - Making cost effectiveness the basis of product selection.

PMID- 16411489
TI  - An insight into the role of the NHS procurement manager.

PMID- 16411490
TI  - Bulk purchasing can improve patient outcomes and save time and money.

PMID- 16411491
TI  - Establishing a formulary for interactive wound-care products.

PMID- 16411492
TI  - Fixational instability and natural image statistics: implications for early
      visual representations.
AB  - Under natural viewing conditions, small movements of the eye, head and body
      prevent the maintenance of a steady direction of gaze. It is known that stimuli
      tend to fade when they are stabilized on the retina for several seconds. However,
      it is unclear whether the physiological motion of the retinal image serves a
      visual purpose during the brief periods of natural visual fixation. This study
      examines the impact of fixational instability on the statistics of the visual
      input to the retina and on the structure of neural activity in the early visual
      system. We show that fixational instability introduces a component in the retinal
      input signals that, in the presence of natural images, lacks spatial
      correlations. This component strongly influences neural activity in a model of
      the LGN. It decorrelates cell responses even if the contrast sensitivity
      functions of simulated cells are not perfectly tuned to counter-balance the power
      law spectrum of natural images. A decorrelation of neural activity at the early
      stages of the visual system has been proposed to be beneficial for discarding
      statistical redundancies in the input signals. The results of this study suggest
      that fixational instability might contribute to the establishment of efficient
      representations of natural stimuli.

PMID- 16411493
TI  - Contextual modulation of orientation tuning contributes to efficient processing
      of natural stimuli.
AB  - It has been proposed that sensory neurons are adapted to the statistical
      structure of the natural environment in order to encode natural stimuli
      efficiently. While spatiotemporal correlations in luminance signals may be
      decorrelated by neurons in early visual processing stages, higher-order
      correlations, such as those in the orientation domain, are likely to persist in
      the input representation until the cortical level. In this study, we first
      examine orientation correlations in natural stimuli across brief time intervals
      and across nearby regions of space, and find strong correlations in both domains.
      We then examine contextual modulation of orientation tuning. We find that both
      temporal and spatial contexts exert a common influence on orientation tuning,
      shifting tuning away from the orientation of either the adapting (temporal) or
      surrounding (spatial) grating. Finally, we incorporate this context-mediated
      repulsive shift in orientation tuning into a model of cortical responses. We find
      that a direct result of the shift is a reduction of the redundancy in the
      population responses evoked by the orientation configurations that are most
      common in natural stimuli. Thus, cortical neurons may be adapted to the
      statistics of orientation in natural stimuli in order to increase the efficiency
      of natural stimulus representation.

PMID- 16411494
TI  - Contrast constancy in natural scenes in shadow or direct light: A proposed role
      for contrast-normalisation (non-specific suppression) in visual cortex.
AB  - The range of contrasts in natural scenes is generally thought to far exceed the
      limited dynamic ranges of individual contrast-encoding neurons in the primary
      visual cortex. The visual system may employ gain-control mechanisms (Ohzawa et
      al. 1985) to compensate for the mismatch between the range of natural contrast
      energies and the limited dynamic range of visual neurons; one proposed mechanism
      is contrast normalisation or non-specific suppression (Heeger 1992a). This paper
      aims to evaluate the role of contrast normalisation in human contrast perception,
      using a computer model of primary visual cortex. The model uses orthogonal pairs
      of Gabor patches to simulate simple-cell receptive-fields to calculate local,
      band-limited contrast in a series of 50 digitised photographs of natural scenes.
      The average range of contrast energies in each image was 2.29 log units, while
      the "lifetime range" each model simple cell would see across all images was 2.98
      log units. These ranges are greater than the dynamic range of real mammalian
      simple cells. Contrast normalisation (dividing contrast responses by the summed
      responses of all nearby neurons) reduces contrast ranges, perhaps sufficiently to
      match them to neurons' limited dynamic ranges. Comparison of images taken under
      diffuse and direct lighting conditions showed that contrast normalisation can
      sometimes match these conditions effectively. This may lead to perceptual
      contrast constancy in the face of spurious changes in contrast caused by natural
      environmental conditions.

PMID- 16411495
TI  - Is the early visual system optimised to be energy efficient?
AB  - This paper demonstrates that a representation which balances natural image
      encoding with metabolic energy efficiency shows many similarities to the neural
      organisation observed in the early visual system. A simple linear model was
      constructed that learned receptive fields by optimally balancing information
      coding with metabolic expense for an entire visual field in a 2-stage visual
      system. The input to the model consists of a space variant retinal array of
      photoreceptors. Natural images were then encoded through a bottleneck such as the
      retinal ganglion cells that form the optic nerve. The natural images represented
      by the activity of retinal ganglion cells were then encoded by many more
      'cortical' cells in a divergent representation. Qualitatively, the system learnt
      by optimising information coding and energy expenditure and matched (1) the
      centre surround organisation of retinal ganglion cells; (2) the Gabor-like
      organisation of cortical simple cells; (3) higher densities of receptive fields
      in the fovea decreasing in the periphery; (4) smaller receptive fields in the
      fovea increasing in size in the periphery; (5) spacing ratios of retinal cells;
      and (6) aspect ratios of cortical receptive fields. Quantitatively, however,
      there are small but significant discrepancies between density slopes which may be
      accounted for by taking optic blur and fixation induced image statistics into
      account. In addition, the model cortical receptive fields are more broadly tuned
      than biological cortical neurons; this may be accounted for by the computational
      limitation of modelling a relatively low number of neurons. This paper shows that
      retinal receptive field properties can be understood in terms of balancing coding
      with synaptic energy expenditure and cortical receptive fields with firing rate
      energy expenditure, and provides a sound biological explanation of why 'sparse'
      distributions are beneficial.

PMID- 16411496
TI  - Nonlinear and higher-order approaches to the encoding of natural scenes.
AB  - Linear operations can only partially exploit the statistical redundancies of
      natural scenes, and nonlinear operations are ubiquitous in visual cortex.
      However, neither the detailed function of the nonlinearities nor the higher-order
      image statistics are yet fully understood. We suggest that these complicated
      issues can not be tackled by one single approach, but require a range of methods,
      and the understanding of the crosslinks between the results. We consider three
      basic approaches: (i) State space descriptions can theoretically provide complete
      information about statistical properties and nonlinear operations, but their
      practical usage is confined to very low-dimensional settings. We discuss the use
      of representation-related state-space coordinates (multivariate wavelet
      statistics) and of basic nonlinear coordinate transformations of the state space
      (e.g., a polar transform). (ii) Indirect methods, like unsupervised learning in
      multi-layer networks, provide complete optimization results, but no direct
      information on the statistical properties, and no simple model structures. (iii)
      Approximation by lower-order terms of power-series expansions is a classical
      strategy that has not yet received broad attention. On the statistical side, this
      approximation amounts to cumulant functions and higher-order spectra
      (polyspectra), on the processing side to Volterra Wiener systems. In this context
      we suggest that an important concept for the understanding of natural scene
      statistics, of nonlinear neurons, and of biological pattern recognition can be
      found in AND-like combinations of frequency components. We investigate how the
      different approaches can be related to each other, how they can contribute to the
      understanding of cortical nonlinearities such as complex cells, cortical gain
      control, end-stopping and other extraclassical receptive field properties, and
      how we can obtain a nonlinear perspective on overcomplete representations and
      invariant coding in visual cortex.

PMID- 16411497
TI  - Learning of somatosensory representations for texture discrimination using a
      temporal coherence principle.
AB  - In order to perform appropriate actions, animals need to quickly and reliably
      classify their sensory input. How can representations suitable for classification
      be acquired from statistical properties of the animal's natural environment? Akin
      to behavioural studies in rats, we investigate this question using texture
      discrimination by the vibrissae system as a model. To account for the rat's
      active sensing behaviour, we record whisker movements in a hardware model. Based
      on these signals, we determine the response of primary neurons, modelled as
      spatio-temporal filters. Using their output, we train a second layer of neurons
      to optimise a temporal coherence objective function. The performance in
      classifying textures using a single cell strongly correlates with the cell's
      temporal coherence; hence output cells outperform primary cells. Using a simple,
      unsupervised classifier, the performance on the output cell population is same as
      if using a sophisticated supervised classifier on the primary cells. Our results
      demonstrate that the optimisation of temporal coherence yields a representation
      that facilitates subsequent classification by selectively conveying relevant
      information.

PMID- 16411498
TI  - Predicting neuronal responses during natural vision.
AB  - A model that fully describes the response properties of visual neurons must be
      able to predict their activity during natural vision. While many models have been
      proposed for the visual system, few have ever been tested against this criterion.
      To address this issue, we have developed a general framework for fitting and
      validating nonlinear models of visual neurons using natural visual stimuli. Our
      approach derives from linear spatiotemporal receptive field (STRF) analysis,
      which has frequently been used to study the visual system. However, prior to the
      linear filtering stage typical of STRFs, a linearizing transformation is applied
      to the stimulus to account for nonlinear response properties. We used this
      approach to compare two models for neurons in primary visual cortex: a nonlinear
      Fourier power model, which accounts for spatial phase invariant tuning, and a
      traditional linear model. We characterized prediction accuracy in terms of the
      total explainable variance, given intrinsic experimental noise. On average,
      Fourier power STRFs predicted 40% of explainable variance while linear STRFs were
      able to predict only 21% of explainable variance. The performance of the Fourier
      power model provides a benchmark for evaluating more sophisticated models in the
      future.

PMID- 16411499
TI  - Critical band masking in optic flow.
AB  - Visual processing has been widely investigated with narrow band stimuli at low
      contrasts. We used a masking paradigm to examine how visual sensitivity under
      these conditions compares with the perception of the direction of heading in real
      scenes (i.e., with dynamic natural images at high contrasts). We first confirmed
      and extended previous studies showing biases in the amplitude distribution for
      spatial frequency, temporal frequency, speed and direction in dynamic natural
      movies. We then measured contrast thresholds for identification of the direction
      of motion for an observer traveling at various speeds. In spite of differences in
      contrast sensitivity and large non-uniformities in the amplitude content of the
      stimuli, contrast thresholds were relatively invariant of spatial frequency and
      completely invariant of temporal frequency, speed and direction. Our results
      suggest that visual processing normalises responses to supra-threshold structure
      at different spatial and temporal frequencies within natural stimuli and so
      equates their effective visibility.

PMID- 16411500
TI  - Multiple views of the response of an ensemble of spectro-temporal features
      support concurrent classification of utterance, prosody, sex and speaker
      identity.
AB  - Models of auditory processing, particularly of speech, face many difficulties.
      These difficulties include variability among speakers, variability in speech rate
      and robustness to moderate distortions such as time compression. In contrast to
      the 'invariance of percept' (across different speakers, of different sexes, using
      different intonation, and so on) is the observation that we are sensitive to the
      identity, sex and intonation of the speaker. In previous work we have reported
      that a model based on ensembles of spectro-temporal feature detectors, derived
      from onset sensitive pre-processing of a limited class of stimuli, preserves
      significant information about the stimulus class. We have also shown that this is
      robust with respect to the exact choice of feature set, moderate time compression
      in the stimulus and speaker variation. Here we extend these results to show a)
      that by using a classifier based on a network of spiking neurons with spike
      driven plasticity, the output of the ensemble constitutes an effective rate
      coding representation of complex sounds; and b) that the same set of spectro
      temporal features concurrently preserve information about a range of
      qualitatively different classes into which the stimulus might fall. We show that
      it is possible for multiple views of the same pattern of responses to generate
      different percepts. This is consistent with suggestions that multiple parallel
      processes exist within the auditory 'what' pathway with attentional modulation
      enhancing the task-relevant classification type. We also show that the responses
      of the ensemble are sparse in the sense that a small number of features respond
      for each stimulus type. This has implications for the ensembles' ability to
      generalise, and to respond differentially to a wide variety of stimulus classes.

PMID- 16411501
TI  - Feature classes for 1D, 2nd order image structure arise from natural image
      maximum likelihood statistics.
AB  - Much is understood of how quantitative aspects of image structure are measured by
      VI simple cells, but less about how qualitative structure is determined from
      these measurements. We review Geometric Texton Theory (GTT) that aims to describe
      this step from quantitative to qualitative. GTT proposes that qualitative feature
      categories arise through consideration of the maximum likelihood (ML)
      explanations of image measurements. It posits that a pair of output vectors of an
      ensemble of co-localised neurons signal the same feature category if and only if
      the corresponding ML explanations are qualitatively similar. We present
      mathematical and empirical results relevant to GTT for the limited case of
      measurement by 1D filters of up to 2nd order. The mathematical results identify
      the simplest explanations for measurements by such filters, while the empirical
      results identify the ML. We find that the ML explanations are not the most simple
      under any of the definitions of simple that we examined. However, the ML
      explanations do have properties predicted by GTT. In particular they change
      rapidly and qualitatively for certain narrow regions of measurement space, while
      remaining qualitative stable between those transition regions. Three feature
      categories arise naturally from the data: light bars, dark bars and edges. The
      results are consistent with GTT.

PMID- 16411502
TI  - Life span effects of lexical factors on oral naming.
AB  - This study investigated how lexical access in naming tasks (picture naming,
      naming to open-ended sentences, and naming to category exemplars) might be
      influenced by different lexical factors during adolescence and adulthood.
      Participants included 1075 individuals, ranging in age from 12 to 83 years.
      Lexical factors examined included word frequency and familiarity, age of
      acquisition, neighborhood density, and phonotactic probability. As expected, each
      of these factors influenced lexical access, and there was a general trend towards
      less accurate naming with age. More interestingly, word frequency and
      neighborhood density both showed larger effects for adolescents than for adults,
      but then showed constant effects on lexical access throughout adulthood.
      Phonotactic probability showed constant effects across the lifespan. Effects of
      word familiarity and age of acquisition interacted with age in adulthood; lexical
      access of older adults was more greatly affected by a word's familiarity and age
      of acquisition than was the lexical access of younger adults. These lexical
      factors impact on adult naming so that words that were learned later in life and
      which are judged to be less familiar are more difficult to retrieve then their
      counterparts (words learned earlier and judged to be more familiar) as
      individuals age. This suggests that age of acquisition and familiarity may play a
      protective role in adult naming. In contrast, word frequency and form-based
      properties of words appear to have similar effects throughout adulthood.
      Implications of these findings for theories of aging and for models of lexical
      access are discussed.

PMID- 16411503
TI  - Alignment of "phrase accent" lows in dutch falling rising questions: theoretical
      and methodological implications.
AB  - In the first part of this study, we measured the alignment (relative to segmental
      landmarks) of the low F0 turning points between the accentual fall and the final
      boundary rise in short Dutch falling-rising questions of the form Do you live in
      [place name]? produced as read speech in a laboratory setting. We found that the
      alignment of these turning points is affected by the location of a postaccentual
      secondary stressed syllable if one is present. This is consistent with the
      findings and analyses of Grice, Ladd, & Arvaniti, 2000 (Phonology 17, 143-185),
      suggesting that the low turning points are the phonetic reflex of a "phrase
      accent." In the second part of this study, we measured the low turning points in
      falling-rising questions produced in a task-oriented dialog setting and found
      that their alignment is affected in the same way as in the read speech data. This
      suggests that read speech experiments are a valid means of investigating the
      phonetic details of intonation contours.

PMID- 16411504
TI  - Japanese listeners' perceptions of phonotactic violations.
AB  - The canonical form for Japanese words is (Consonant)Vowel(Consonant) Vowel-.
      However, a regular process of high vowel devoicing between voiceless consonants
      and word-finally after voiceless consonants results in consonant clusters and
      word-final consonants, apparent violations of that phonotactic pattern. We
      investigated Japanese adults' perceptions of these violations, asking them to
      rate both canonical and noncanonical nonsense forms on a scale of goodness.
      Results indicate that adults show evidence of being guided in making their
      judgments by an implicit understanding of both typical canonical forms and
      appropriate contexts for vowel devoicing.

PMID- 16411505
TI  - Sentential context and the interpretation of familiar open-compounds and novel
      modifier-noun phrases.
AB  - Two experiments investigated the influence of sentential context on the relative
      ease of deriving a particular meaning for novel and familiar compounds.
      Experiment 1 determined which of two possible meanings was preferred for a set of
      novel phrases. Experiment 2 used both novel (e.g., brain sponge) and familiar
      compounds (e.g., bug spray). The compounds appeared in a sentential context that
      supported either the dominant or subdominant meaning. Next, participants saw
      either the dominant or subdominant definition and indicated whether it was
      plausible. When the definition was consistent with the preceding sentence, the
      participants were more likely to consider the definition plausible regardless of
      whether the compound was novel or familiar, although this difference was more
      pronounced for novel phrases than for familiar phrases. In terms of response
      times, the effect of sentential context also depended on the degree of dominance.
      The data suggest that the interpretation of compounds is affected by at least two
      sources of information: sentential context and the relative dominance of the
      preferred meaning.

PMID- 16411506
TI  - How do syllables contribute to the perception of spoken English? insight from the
      migration paradigm.
AB  - The involvement of syllables in the perception of spoken English has
      traditionally been regarded as minimal because of ambiguous syllable boundaries
      and overriding rhythmic segmentation cues. The present experiments test the
      perceptual separability of syllables and vowels in spoken English using the
      migration paradigm. Experiments 1 and 2 show that syllables migrate considerably
      more than full and reduced vowels, and this effect is not influenced by the
      lexicality of the stimuli, their stress pattern, or the syllables' position
      relative to the edge of the stimuli. Experiment 3 confirms the predominance of
      syllable migration against a pseudosyllable baseline, and provides some evidence
      that syllable migration depends on whether syllable boundaries are clear or
      ambiguous. Consistent with this hypothesis, Experiment 4 demonstrates that CVC
      syllables migrate more in stimuli with a clear CVC-initial structure than in
      ambisyllabic stimuli. Together, the data suggest that syllables have a greater
      contribution to the perception of spoken English than previously assumed.

PMID- 16411507
TI  - Transformation of a leprosy hospital in Nepal into a rehabilitation centre: the
      Green Pastures Hospital experience.
AB  - Green Pastures Hospital for leprosy patients in Pokhara Nepal, was established in
      1957 by the International Nepal Fellowship (INF) in a decade which saw the
      establishment of many similar hospitals in other leprosy endemic countries. In
      recent years, mainly due to significant improvements in leprosy control services
      and the wide implementation of multiple drug therapy (MDT) for all patients, many
      of these specialist hospitals have encountered 1) a decline in prevalence rate,
      2) a large decline in the percentage of patients presenting with WHO grade 2
      disability, 3) a decline in the previous indications for hospital admission, e.g.
      immunologically mediated reactions, and 4) a need to develop financial
      independence making them less dependent on donor agencies. In addition, the
      decision to change from specialist to general services opened up the possibility
      of using facilities and expertise for the rehabilitation of non-leprosy affected
      persons, whilst also moving towards the reduction of stigma and prejudice against
      patients with leprosy. This paper describes the process of 'transformation' of an
      established and well known leprosy hospital in Western Nepal from 1997 onwards
      into a general rehabilitation hospital. Careful preparation, with full
      involvement of existing staff and co-operation with other agencies in the
      hospital catchment area were key factors in what has now become a successful
      venture. Surgical procedures and orthopaedic appliance services for non-leprosy
      affected persons have increased in recent years and the introduction of a
      dermatology service has resulted in out-patient attendance rising from about 1000
      in 1999 to 4500 in 2003. No evidence of reluctance to attend and use the
      facilities offered by this hospital because of stigma against leprosy has been
      encountered. Many of the changes described have been made in order to reduce
      financial dependence on donor sources of support, but the underlying reason for
      transformation is still based on the vision of the INF mission to work for and
      improve the condition of the marginalized in society.

PMID- 16411509
TI  - An analysis of the pattern of detection of leprosy patients by institutions in
      the general health services in Sri Lanka after the integration of leprosy
      services into general health services.
AB  - Integration of leprosy services into the General Health Services was initiated in
      2001 in Sri Lanka, and by the end of 2003 all services related to leprosy care
      were fully integrated. Against this background, routinely collected data
      available at the Anti-Leprosy Campaign for a 3-year period from 2000-2003 were
      analyzed to identify the pattern of the detection of cases by hierarchical
      institutions in the General Health Services. The analysis showed that more than
      75% of leprosy patients had been detected at base, general and teaching hospitals
      and this trend was increasing proportionally during the period of concern (P <
      0.001). Teaching hospitals had detected more than 50% of patients and this trend
      was also proportionally increasing. Nearly one-third of patients detected at
      teaching hospitals had been detected at the Central Leprosy Clinic (CLC) at the
      National Hospital. The trend for case detection at the CLC was decreasing
      proportionally and in absolute terms during the 3-year period after integration.
      More than 60% of leprosy patients had been detected at institutions where
      consultant dermatologists were available. The analysis concluded that centralized
      leprosy diagnostic and treatment services have been taken over by the
      institutions in the General Health Services but within districts these activities
      are predominantly concentrated on higher level institutions with consultant
      dermatological services. This suggests that similar to the existing general trend
      of by passing of lower level institutions by patients to seek treatment at higher
      level institutions, which are perceived to provide a service of better quality,
      leprosy patients too prefer to seek treatment at these institutions.

PMID- 16411508
TI  - The INFIR Cohort Study: assessment of sensory and motor neuropathy in leprosy at
      baseline.
AB  - AIM: To compare different method(s) to detect peripheral neuropathy in leprosy
      and to study the validity of the monofilament test (MF) and the voluntary muscle
      test (VMT) as standard tests of nerve function. DESIGN: A multi-centre cohort
      study of 303 multibacillary (MB) leprosy patients. METHODS: Newly registered MB
      patients requiring a full course of MDT were recruited in two leprosy outpatient
      clinics in North India. Controls were people without leprosy or neurological
      conditions, attending the dermatological outpatient departments of the same
      clinics. Nerve function was evaluated electrophysiologically using standard
      parameters for sensory and motor nerve conduction (NC) testing, warm and cold
      detection thresholds (W/CDT), vibration perception thresholds, dynamometry, MF
      and VMT. The latter two defined the outcomes of sensory and motor impairment.
      RESULTS: 115 patients had nerve damage or a reaction of recent onset at
      diagnosis. Sensory and motor amplitudes and WDTs were the most frequently
      abnormal. Among the nerves tested, the sural and posterior tibial were the most
      frequently impaired. In the ulnar nerve, sensory latencies were abnormal in 25%
      of subjects; amplitudes in 40%. Ulnar above-elbow motor conduction velocities
      were abnormal in 39% and amplitudes 32%. WDTs were much more frequently affected
      than CDTs in all nerves tested. The thresholds of all test parameters differed
      significantly between controls and patients, while only some differed between
      patients with and without reaction. Good concordance was observed between MF
      results and sensory latencies and velocities (direct concordance 80% for the
      ulnar). However, a proportion of nerves with abnormal MF results tested normal on
      one or more of the other tests or vice versa. Concordance between VMT and motor
      conduction velocities was good for the ulnar nerve, but for the median and
      peroneal nerves, the proportion impaired by VMT out of those with abnormal motor
      conduction was very low. CONCLUSIONS: Concordance between monofilaments and other
      sensory function test results was good, supporting the validity of the
      monofilaments as standard screening test of sensory function. Concordance between
      VMT results and motor nerve conduction was good for the ulnar nerve, but very few
      median and peroneal nerves with abnormal conduction had an abnormal VMT. A more
      sensitive manual motor test may be needed for these nerves. Of the nerve
      assessment tests conducted, NC amplitudes and warm sensation were the most
      frequently affected. Therefore, nerve conduction studies and WDT measurements
      appear to be most promising tests for early detection of leprous neuropathy. The
      pattern of concordance between tactile and thermal sensory impairment failed to
      support the hypothesis that small fibre neuropathy always precedes large fibre
      damage. Warm sensation was more frequently affected than cold sensation. This
      could indicate that unmyelinated C fibres are more frequently affected than small
      myelinated Asigma fibres.

PMID- 16411510
TI  - Risk factors for participation restriction in leprosy and development of a
      screening tool to identify individuals at risk.
AB  - The World Health Organisation International Classification of Functioning,
      Disability and Health defines participation as involvement in a life situation.
      Participation restrictions are problems experienced in any life situation, for
      example, in relationships or in employment. Our research explored risk factors
      for participation restrictions experienced by people affected by leprosy. Our
      objective was to develop a screening tool to identify individuals at risk. An
      initial round of qualitative fieldwork in eight centres in Nepal, India and
      Brazil identified 35 potential risk factors for participation restriction. These
      were then further assessed through quantitative fieldwork in six centres in India
      and Brazil. In all, 264 individuals receiving leprosy treatment or rehabilitation
      services made a retrospective assessment of their status at time of diagnosis.
      Their level of participation restriction was assessed using the Participation
      Scale. Regression analysis identified risk factors for participation restriction
      including fear of abandonment by family members (odds ratio 2.63, 95% CI 1.35
      5.13) and hospitalization at diagnosis (3.98, 1.0-7.32). We recommend four
      consolidated items as the basis for a simple screening tool to identify
      individuals at risk. These are the physical impact of leprosy, an emotional
      response to the diagnosis, female gender and having little or no education. Such
      a tool may form the basis for a screening and referral procedure to identify
      newly diagnosed individuals at risk of participation restrictions and in need of
      actions that may prevent such restrictions.

PMID- 16411511
TI  - STEP: an intervention to address the issue of stigma related to leprosy in
      Southern Nepal.
AB  - This paper focuses primarily on the extent to which a Stigma Elimination
      Programme (STEP) affected the social participation of people affected by leprosy
      in southern Nepal. The Participation Scale (popularly known as The P Scale) was
      applied to compare leprosy affected people who participated in STEP groups with a
      control group comprising leprosy affected people who lived in villages where STEP
      had not been implemented. It was found that STEP participants had significantly
      higher levels of participation compared with controls and that their levels of
      social participation were higher than would be expected even for the general
      population. It was also found that leprosy affected people without visible
      deformity or ulceration (whether in the STEP group or not) do not appear to
      suffer participation restriction in southern Nepal.

PMID- 16411512
TI  - Assessment of the quality of leprosy services from the clients' perspective in
      Thailand.
AB  - To assess the quality of the leprosy service in health facilities from the
      clients' perspective, qualitative data collection methods, i.e. semi-structured
      interviews, focus group discussions (FGDs) and priority cards, were conducted in
      six health facilities located in all regions of Thailand. A total of 29 patients
      were interviewed and three focus group discussions involving 20 patients were
      carried out. In addition, six health staff and six community members were
      interviewed. The results show that patients delayed months to years before they
      went to a public health facility. This is due to the poor knowledge about
      leprosy. Most of the interviewed patients tried to get rid of the skin symptoms
      at home, using topical medicated cream or herbs. Distance was not regarded as a
      problem, because most patients go to nearby district hospitals. In district
      hospitals misdiagnosis is still common. More than half of leprosy patients said
      they did not receive any information about leprosy before they were diagnosed.
      Travel costs seem to cause problems for a few poor and aged patients who needed
      someone to accompany them. Patients at district and provincial hospitals
      complained that the waiting times to consult staff were too long. In most health
      facilities, privacy during examinations was not adequate. Patients placed a
      priority on health staff being friendly and respectful to them. When patients
      were asked to list their priorities of the quality of services, they considered
      the attitude of health staff, low costs to go to the leprosy services, adequate
      attention to POD and adequate information to leprosy patients on their disease,
      as their top four items. Important recommendations resulting from the study were:
      (1) health education to the public has to be strengthened; (2) training of health
      staff to minimize doctors' delay; (3) good attitude of health staff towards
      leprosy patients should be sustained; and (4) leprosy services in district and
      provincial hospitals should be improved as a one-stop service for leprosy
      patients.

PMID- 16411513
TI  - Qualitative assessment of social, economic and medical needs for ex-leprosy
      patients living in leprosy villages in Shandong Province, The People's Republic
      of China.
AB  - After successful control of the endemic of leprosy in Shandong Province, China,
      how to deal with ex-leprosy patients living in the leprosy villages/leprosaria
      has become a hot topic among programme managers, medical staff and governmental
      officials at different levels. One of the possible solutions in dealing with the
      problem was proposed to combine small leprosy villages into a few larger, already
      existing, leprosaria/leprosy villages with better facilities, in order to provide
      better care for ex-leprosy patients and make better use of existing resources.
      With this assumption, social, economic and medical needs felt by ex-leprosy
      patients in three leprosy villages of Shandong province were assessed
      qualitatively, and the possibilities and obstacles regarding combination were
      explored. The results showed that the basic needs for living, such as food and
      clothes, were provided by state governments, although living standards remained
      at a low level. Medical care was not satisfactory, as many health problems
      related and unrelated to leprosy were increasing, and self-care needed to be
      addressed, as the dependents grew older and the disability status became worse.
      Although the majority of ex-leprosy patients, medical staff and government
      officials interviewed agreed with the idea of the adjustment of leprosy
      villages/leprosaria, some obstacles, including stigma, existed. Government
      commitment, ideally at top level, was needed in order to facilitate the process
      of combination.

PMID- 16411514
TI  - Availability of records and reports in health facilities under integrated leprosy
      services of India.

PMID- 16411515
TI  - Septicemia, access, cardiovascular disease, and death in dialysis patients.

PMID- 16411516
TI  - Laparoscopy for PD catheter placement: advantages and disadvantages versus
      peritoneoscopy.

PMID- 16411517
TI  - Safe, simple, effective PD catheters--now affordable and available.

PMID- 16411518
TI  - Simultaneous removal and reinsertion of peritoneal dialysis catheters: do we know
      why and when?

PMID- 16411519
TI  - Erythropoietic agents in peritoneal dialysis.

PMID- 16411520
TI  - Minilaparoscopic extraperitoneal tunneling with omentopexy: a new technique for
      CAPD catheter placement.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is an effective form
      of treatment for patients with end-stage renal disease. Open insertion of
      peritoneal dialysis (PD) catheters is the standard surgical technique, but it is
      associated with a relatively high incidence of catheter-related problems. To
      overcome these problems, different laparoscopic techniques have been presented,
      being preferable to the open and percutaneous methods. OBJECTIVE: To introduce
      and evaluate the efficiency of laparoscopic omental fixation and extraperitoneal
      placement of the cuff-coil part (the straight portion) of the catheter to prevent
      catheter tip migration, pericatheter leakage, severe abdominal pain, and the
      obstruction caused by omental wrapping. SETTING: The study was carried out in the
      General Surgery Department, Akdeniz University Medical School, in Turkey.
      PATIENTS AND METHODS: Between November 2001 and March 2005, the technique was
      applied in 44 consecutive patients (mean age 51.6 years, range 18 - 67 years)
      with end-stage renal disease. During this laparoscopic technique, the omentum was
      first fixed onto the parietal peritoneum, and then the catheter was introduced
      through the subumbilical trocar site into the posterior rectus compartment and
      advanced toward the symphysis pubis. The catheter was then inserted into the
      abdominal cavity, passing the peritoneal opening, which was prepared before
      catheter insertion. The straight portion of the catheter was located into the
      extraperitoneal area of the anterior abdominal wall. The curled end, which
      contains the side-holes of the catheter, was placed into the true pelvis.
      Catheter position and patency were verified under direct vision using a 2 mm
      telescope. RESULTS: All procedures were completed laparoscopically. Operating
      time ranged between 40 and 100 minutes (median 52 minutes). There was no
      intraoperative complication or surgical mortality. Peritoneal dialysis was
      initiated within 15 - 24 hours after catheter implantation. After a median follow
      up period of 17.4 months (range 1 - 38 months), early exit-site infection
      occurred in 1 of 44 patients. All catheters functioned well postoperatively.
      There was no pain during CAPD. CONCLUSION: This new laparoscopic technique using
      an extraperitoneal approach with omentopexy for PD catheter placement could prove
      extremely useful for preventing catheter malfunction caused by catheter tip
      migration, pericatheter leakage, omental wrapping, and periodic catheter movement
      that causes abdominal pain in CAPD.

PMID- 16411521
TI  - Early start of CAPD with the Seldinger technique.
AB  - The ideal method for inserting continuous ambulatory peritoneal dialysis (PD)
      catheters remains debatable. Minimally invasive techniques are becoming more
      popular. The routine recommendation for starting PD is 4 - 6 weeks after catheter
      insertion. We planned a prospective study to evaluate whether this waiting period
      is necessary. From January 2003 to July 2004, 42 double-cuff Tenckhoff CAPD
      catheters were inserted into 41 patients. Percutaneous technique was used and PD
      was started on the sixth day. Only 2 pericatheter leakages (4.8%) were detected.
      This procedure is comparatively safe, simple, and less costly than surgical and
      peritoneoscopic placement. The rate of early pericatheter leakage may be lowered
      with this technique and PD may be started earlier.

PMID- 16411522
TI  - Treatment of refractory pseudomonas aeruginosa exit-site infection by
      simultaneous removal and reinsertion of peritoneal dialysis catheter.
AB  - BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) with
      Pseudomonas aeruginosa exit-site infection (ESI) refractory to antibiotic
      treatment often require replacement of their peritoneal dialysis catheter (PDC).
      The optimal interval between removal and reinsertion of the PDC is not known.
      There are relatively few data on the feasibility of simultaneous removal and
      reinsertion of dialysis catheters for the treatment of P. aeruginosa ESI.
      METHODS: We retrospectively reviewed the short- and long-term outcomes of all
      CAPD patients who had undergone simultaneous removal and reinsertion of their PDC
      for the treatment of refractory P. aeruginosa ESI in our hospital between January
      1994 and December 2003. During the operation, the old catheter was removed first
      and a new catheter was inserted into the opposite side of the abdomen. All
      patients received 7 days of antibiotic therapy postoperatively. CAPD was resumed
      after 2 weeks of intermittent peritoneal dialysis. RESULTS: Over a 10-year
      period, 37 CAPD patients underwent the operation. Mean age of the patients was
      59.5 +/- 10.9 years. The interval between the diagnosis of ESI and the operation
      was 16.7 +/- 6.9 weeks. The patients received 7.6 +/- 2.5 weeks of antibiotic
      treatment before the procedure. Early postoperative complications were uncommon.
      None of the patients developed ESI within 4 weeks after the operation. At 1 year
      after the operation, 3 patients (8%) had developed recurrence of P. aeruginosa
      ESI 24 - 40 weeks postoperatively. Peritonitis due to P. aeruginosa was not
      observed. CONCLUSIONS: We conclude that simultaneous removal and reinsertion of
      the PDC is feasible in eradicating refractory ESI due to P. aeruginosa. This
      procedure alleviates the need for temporary hemodialysis and allows continuation
      of peritoneal dialysis.

PMID- 16411524
TI  - Pharmacokinetics of calcitriol and maxacalcitol administered into peritoneal
      dialysate bags in peritoneal dialysis patients.
AB  - OBJECTIVES: It is well known that injection of calcitriol (CT) or maxacalcitol
      (OCT) is very effective in hemodialysis patients with secondary
      hyperparathyroidism (2HPT). However, it is difficult to use these drugs with
      peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected
      two or three times per week. The objective of the present study was to evaluate
      the stability of physiological activities of CT and OCT in PD bags and to
      determine the CT or OCT dosage for intraperitoneal (IP) administration. MATERIALS
      AND METHODS: We added CT 1.5 microg or OCT 10 microg to Dianeal PD-2 (approximate
      pH = 5.0, calcium = 0.87 mmol/L; Baxter,Tokyo, Japan), Midpeliq 250 (approximate
      pH = 7.0, Ca = 1.0 mmol/L;Terumo Corporation, Tokyo, Japan), and Peritoliq 250
      (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were
      collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition
      of CT and OCT. The activities of CT and OCT in the dialysis effluent were
      measured by radioimmunoassay. The levels of serum and effluent OCT after a single
      IP administration of 10 microg OCT were examined in 4 PO patients with advanced
      2HPT. RESULTS: Although the levels of CT and OCT in PD bags made of polyvinyl
      resins decreased by 70% - 75% immediately after injection, levels in PD bags made
      of polypropylene resins decreased only slightly. The concentration of CT mixed
      into the acidic solution in glass containers was stable; the decreased
      concentration of CT in the PD solution might be due to adsorption onto polyvinyl
      resins. The maximum serum concentration after IP administration of 10 microg OCT
      was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These
      results show good peritoneal transport of OCT but not rapid disappearance, unlike
      intravenous administration. CONCLUSIONS: If peritoneal administration of vitamin
      D derivatives is contemplated, it is important to select the composition of PD
      bag resins, type of vitamin D analog, and time lag to use when deciding the
      dosage of injectable vitamin D preparations, such as OCT or CT, for IP
      administration to PD patients. It appears that IP administration in overnight
      dwells might be useful for PD patients as a complementary vitamin D preparation.

PMID- 16411523
TI  - Efficient monthly subcutaneous administration of darbepoetin in stable CAPD
      patients.
AB  - BACKGROUND: Although subcutaneous administration of recombinant human
      erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD)
      patients is a widely accepted recommendation, the lowest possible frequency of an
      efficient dosing regimen remains controversial. Darbepoetin alpha, a new
      erythropoiesis-stimulating protein with a threefold longer serum half-life
      compared with rHuEPO, has greater in vivo potency and can be administered less
      frequently to obtain the same biological response. This study assessed the
      efficacy of darbepoetin administered once monthly in the treatment of anemia in
      CAPD patients. PATIENTS AND METHODS: In this single-center, prospective cohort
      study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 +/- 14.1 years;
      mean duration on peritoneal dialysis 31.6 +/- 13 months) maintained average
      hemoglobin and hematocrit levels of 12.09 +/- 1.29 g/dL and 37.29% +/- 3.58%,
      respectively, while receiving a mean weekly maintenance dose of epoetin alfa of
      129 IU/kg. These same patients were assigned to receive the equivalent weekly
      darbepoetin dose once monthly for 24 consecutive weeks. Hematological response,
      iron status (transferrin saturation, serum ferritin levels), C-reactive protein
      (CRP), and the patients' biochemical profiles were evaluated monthly. RESULTS:
      During the monthly administration of darbepoetin, mean serum levels of Hb and Hct
      were 12.17 +/- 1.28 g/dL and 37.1% +/- 1.19% respectively. No statistically
      significant difference was apparent between the previous and monthly dosing
      values (12.09 +/- 1.29 vs 12.17 +/- 1.28 g/dL, p = 0.769, and 37.29% +/- 3.58% vs
      37.1% +/- 1.19%, p = 0.752). Transferrin saturation levels as well as serum
      ferritin levels also remained unchanged (30.4% +/- 8.6% vs 30.1% +/- 9.4%, NS,
      and 556 +/- 212 vs 621 +/- 234 ng/mL, respectively, NS). CONCLUSION: These
      results indicate that darbepoetin alfa can be effectively given subcutaneously at
      monthly intervals for the treatment of anemia in stable CAPD patients. However,
      more studies are needed to validate the long-term efficacy of this monthly
      subcutaneous administration.

PMID- 16411525
TI  - Effect of oral administration of losartan, prazosin, and verapamil on peritoneal
      solute transport in continuous ambulatory peritoneal dialysis patients.
AB  - BACKGROUND: Several intraperitoneally administered drugs have been shown to
      modify transport of peritoneal solute and fluid. Fewer studies, however, have
      evaluated the effect of orally administered drugs. The present study was
      performed to evaluate the effects of oral losartan, prazosin, and verapamil on
      peritoneal membrane transport during a peritoneal equilibration test (PET), as
      well as the effects on creatinine clearance (CrCl), Kt/V urea, 24-hour protein in
      drained dialysate, and drained volume. METHODS: This was an open, controlled,
      crossover clinical trial performed in 20 patients on continuous ambulatory
      peritoneal dialysis. All subjects used four 2-L 1.5% glucose dialysis exchanges
      per day. After a 7-day washout period (without antihypertensives), they had a
      baseline standard PET and dialysis adequacy assessment performed. Subsequently,
      they were randomly allocated to receive the first of three study drugs (losartan,
      prazosin, and verapamil), which were administered orally for a 7-day period.
      Immediately after each drug period, patients had a new 3-day washout and
      subsequently started the next drug, until they had received each of the three
      drugs. On the last day of administration of each drug, patients were subjected to
      a new PET and adequacy of dialysis evaluation. RESULTS: None of the studied drugs
      significantly modified the peritoneal transport of creatinine, glucose, urea,
      sodium, potassium, or total protein as evaluated by PET. Verapamil significantly
      increased peritoneal CrCl [51.3 (44.3 - 53.3) vs baseline 45.8 (41.4 - 50.5)
      L/week/ 1.73 m2, p < 0.05], weekly Kt/V urea [1.75 (1.60 - 1.78) vs baseline 1.59
      (1.54 - 1.73), p < 0.05], and drained dialysate volume [8.80 (8.30 - 8.96) vs
      baseline 8.44 (8.20 - 8.50) L/day, p < 0.05]. CONCLUSIONS: Oral administration of
      losartan, prazosin, and verapamil did not modify the peritoneal transport of
      solutes during a 4-hour PET. Oral verapamil significantly increased CrCl, Kt/V
      urea, and 24-hour drained dialysate volume. It is most likely that verapamil
      increases peritoneal (hydraulic) conductivity, and then net ultrafiltration
      volume and convective transport of urea, creatinine, and protein. Verapamil could
      be considered as an alternative in patients requiring increased dialysis dose
      and/or ultrafiltration.

PMID- 16411526
TI  - Take care in how you store your PD fluids: actual temperature determines the
      balance between reactive and non-reactive GDPs.
AB  - OBJECTIVE: During heat sterilization and during prolonged storage, glucose in
      peritoneal dialysis fluids (PDF) degrades to carbonyl compounds commonly known as
      glucose degradation products (GDPs). Of these, 3,4-dideoxyglucosone-3-ene (3,4
      DGE) is the most cytotoxic. It is an intermediate in degradation between 3
      deoxyglucosone (3-DG) and 5-hydroxymethyl-2-furaldehyde (5-HMF). We have earlier
      reported that there seems to be equilibrium between these GDPs in PDF. The aim of
      the present study was to investigate details of this equilibrium. METHODS:
      Aqueous solutions of pure 3-DG, 3,4-DGE, and 5-HMF were incubated at 40 degrees C
      for 40 days. Conventional and low-GDP fluids were incubated at various
      temperatures for up to 3 weeks. Formaldehyde, acetaldehyde, glyoxal,
      methylglyoxal, 3-DG, 3,4-DGE, and 5-HMF were analyzed using high performance
      liquid chromatography. RESULTS: Incubation of 100 micromol/L 3,4-DGE resulted in
      the production of 36 micromol/L 3-DG, 4 micromol/L 5-HMF, and 40 micromol/L
      unidentified substances. With the same incubation, 200 micromol/L 3-DG was
      converted to 9 micromol/L 3,4-DGE, 6 micromol/L 5-HMF, and 14 micromol/L
      unidentified substances. By contrast, 100 micromol/L 5-HMF was uninfLuenced
      byincubation. In a conventional PDF incubated at 60 degrees C for 1 day, the 3,4
      DGE concentration increased from 14 to a maximum of 49 micromol/L. When the
      fluids were returned to room temperature, the concentration decreased but did not
      reach original values until after 40 days. In a low GDP fluid, 3,4-DGE increased
      and decreased in the same manner as in the conventional fluid but reached a
      maximum of only 0.8 micromol/L. CONCLUSIONS: Considerable amounts of 3,4-DGE may
      be recruited by increases in temperature in conventional PDFs. Lowering the
      temperature will again reduce the concentration but much more time will be
      needed. Precursors for 3,4-DGE recruitment are most probably 3-DG and the enol 3
      deoxyaldose-2-ene, but not 5-HMF. Considering the ease at which 3,4-DGE is
      recruited from its pool of precursors and the difficulty of getting rid of it
      again, one should be extremely careful with the temperatures conventional PDFs
      are exposed to.

PMID- 16411527
TI  - Influence of icodextrin on plasma and dialysate levels of N(epsilon)
      (carboxymethyl)lysine and N(epsilon)-(carboxyethyl)lysine.
AB  - RATIONALE: Standard peritoneal glucose solutions may induce the formation of
      advanced glycation end products (AGEs). Preliminary data suggest that AGE
      formation may be less with the use of polyglucose solutions (icodextrin).
      Therefore, we investigated whether the use of icodextrin for the long dwell would
      result in a reduction in plasma and dialysate levels of the AGE products
      N(epsilon)-(carboxymethyl) lysine (CML) and N(epsilon)-(carboxyethyl) ysine
      (CEL). PATIENTS AND METHODS: 40 patients were randomized to treatment with
      standard glucose solutions (1.36%) and icodextrin for the long dwell during a 4
      month study period; 32 patients completed the study. CML was assessed by stable
      isotope dilution/tandem mass spectrometry. RESULTS: CML levels in plasma
      increased significantly in patients treated with icodextrin (0.146 +/- 0.056 at
      start vs 0.188 +/- 0.069 micromol/mmol Lys at the end of the study, p < 0.0001)
      but did not change in the control group (0.183 +/- 0.090 vs 0.188 +/- 0.085
      micromol/mmol Lys). The same held true for CML levels in dialysate (0.28 +/- 0.09
      at start vs 0.33 +/- 0.11 micromol/mmol Lys at the end of the study, p < 0.025).
      No change was observed in patients treated with the control solutions (0.31 +/-
      0.11 at start vs 0.31 +/- 0.07 micromol/mmol Lys). CONCLUSION: Contrary to the
      hypothesis, plasma and dialysate levels of CML increased in patients treated
      using icodextrin for the long dwell.

PMID- 16411528
TI  - Hepatic subcapsular steatosis as a complication associated with intraperitoneal
      insulin treatment in diabetic peritoneal dialysis patients.
AB  - OBJECTIVES: The aim of this study was to evaluate hepatic subcapsular steatosis
      (HSS) and its association with clinical parameters in nondiabetic continuous
      ambulatory peritoneal dialysis (CAPD) patients and in diabetic CAPD patients
      receiving intraperitoneal (IP) or subcutaneous (SC) insulin. DESIGN: Cross
      sectional study. SETTING: A tertiary-care university hospital. PATIENTS: 28 CAPD
      patients (17 males and 11 females; mean age 53.5 +/- 14 years; mean CAPD duration
      22.8 +/- 9 months) were included in the study. 14 patients had type II diabetes
      mellitus and 14 were nondiabetics. In the diabetic group, 8 patients were
      receiving IP insulin and 6 were receiving SC insulin. OUTCOME MEASURES: HSS was
      diagnosed on computed tomography without contrast administration. Other data
      collected were body mass index (BMI), weekly Kt/V, peritoneal equilibration test
      (PET) results, daily insulin dosage, duration of diabetes mellitus, duration of
      insulin treatment, dialysate glucose load, and serum findings for alanine
      aminotransferase, aspartate aminotransferase, albumin, and lipid profiles.
      RESULTS: HSS was detected in 5 of the 8 diabetics who were receiving IP insulin.
      None of the diabetics receiving SC insulin and none of the nondiabetic patients
      exhibited HSS. Daily insulin dosage [108 (95 - 108.5) vs 54 (36 - 72) U/day, p =
      0.02], BMI [31 (30.5 - 36) vs 26.6 (26 - 30) kg/m2, p = 0.02], serum triglyceride
      level [194 (184 - 505) vs 69 (61 - 82) mg/dL, p = 0.04], and PET creatinine
      levels [D/P2 creat: 0.67 (0.54 - 0.74) vs 0.50 (0.50 - 0.56), p = 0.05; D/P4
      creat: 0.75 (0.64 - 0.86) vs 0.60 (0.59 - 0.62), p = 0.02] were higher in
      diabetic patients receiving IP insulin who had HSS than in those who did not have
      HSS. PET glucose levels [D0/D2 glu: 0.40 (0.37 - 0.45) vs 0.50 (0.48 - 0.51), p =
      0.03; D0/D4 glu: 0.36 (0.26 - 0.38) vs 0.44 (0.38 - 0.48), p = 0.04] were lower
      in diabetic patients receiving IP insulin who had HSS than in those who did not
      have HSS. CONCLUSIONS: Our results suggest that IP insulin plays a more important
      role in the pathogenesis of HSS than glucose levels in diabetic CAPD patients.
      They also indicate that HSS is associated with higher daily insulin requirement,
      obesity, hypertriglyceridemia, and high peritoneal transport rate in diabetic
      CAPD patients receiving IP insulin.

PMID- 16411529
TI  - Efficacy of polyethylene glycol in constipated CAPD patients.

PMID- 16411531
TI  - Avoidance of hepatitis C transmission: a major advantage for PD in an Indian
      center.

PMID- 16411530
TI  - A higher magnesium dialysate concentration treats hypomagnesemia.

PMID- 16411532
TI  - Simultaneous reconstruction of groin hernia and placement of peritoneal dialysis
      catheter.

PMID- 16411534
TI  - Does sclerosing peritonitis induce MIA syndrome and generalized sclerosis?

PMID- 16411533
TI  - Successful treatment of severe Mycobacterium fortuitum exit-site infection with
      preservation of the Tenckhoff catheter.

PMID- 16411535
TI  - How slashing Medicaid hurts children--and children's hospitals.

PMID- 16411537
TI  - Ventriculoperitoneal shunt infections in patients with hydrocephalus.
AB  - Ventriculoperitoneal (VP) shunt infections can be detrimental to the pediatric
      patient with hydrocephalus and his or her family. Although there are many causes
      of hydrocephalus in the pediatric patient, the standard treatment of care is
      surgical placement of a VP shunt. Current treatment modalities when a
      ventriculoperitoneal shunt infection has occurred and the differences between the
      causes of late and early shunt infections are reviewed. Most importantly, the
      signs and symptoms that the families of the child undergoing a VP shunt must know
      during the postoperative period, and the tools they can use to help combat and
      prevent VP shunt infections are discussed.

PMID- 16411536
TI  - Outcomes in children experiencing neurologic insults as preterm neonates.
AB  - Germinal matrix-intraventricular hemorrhage, periventricular hemorrhagic
      infarction, and periventricular leukomalacia are common brain injuries in preterm
      infants that can have significant long-term influences on children's development,
      physical skills, and cognitive functioning. Characteristics of preterm infants,
      including immature cerebrovascular autoregulation, fragility of blood vessels,
      and the presence of the germinal matrix, increase their vulnerability to
      neurologic injury. Grades I-II germinal matrix-intraventricular hemorrhage tends
      to have little-to-moderate long-term impact on cognitive and neuromotor
      development after the neonatal period, while more severe hemorrhage is associated
      with less optimistic developmental prognoses. Periventricular leukomalacia and
      ventriculomegaly in the neonate are associated with severe cognitive disabilities
      as well as with cerebral palsy. Neurodevelopmental strategies emerging from both
      the neonatal developmental care and early intervention models may have a place in
      the post-acute care of newborns who experienced these insults. Vigilant
      developmental screening and early developmental intervention are essential
      components of the follow-up nursing care for children whose medical histories
      include neonatal brain injury.

PMID- 16411538
TI  - Pediatric spinal injuries.
AB  - Spinal injuries in children present unique challenges. The anatomy of the growing
      child affects injury patterns and subsequent care. There are many challenges for
      the child and family, but current research is providing hope for the future.

PMID- 16411539
TI  - Maternal stress and the white coat syndrome: a case study.
AB  - Coping with the birth of a preterm infant is a stressful event for mothers for
      many reasons, including parental role alterations, perception of the infant's
      illness severity, and uncertainty about the infant's prognosis. Stressors evoke
      many physiological responses. Fingertip temperature, an electrophysiologic
      indicator, is a good measure of stress. This case study describes the experience
      of one mother's negative response to a surgeon's visit to her baby's bedside.
      Researchers refer to the "white coat" syndrome, in which personnel can
      significantly affect autonomic function. Increasing our understanding of maternal
      stress could help ameliorate some of the deleterious effects persistently
      elevated levels of stress can produce. Further research might focus on the
      effects of communication with other familiar health care professionals, as well
      as the influence of Kangaroo Care (skin-to-skin, chest-to-chest contact between
      caregiver and infant) on maternal stress.

PMID- 16411540
TI  - The redefinition of failure to thrive from a case study perspective.
AB  - Explaining failure to thrive (FTT) in dichotomous terms--organic versus non
      organic --no longer applies in the context of modern pediatric nursing. FTT has
      turned out to be much more multifaceted. One infant's story illustrates the
      complexities and long-term ramifications of a pediatric feeding disorder and the
      challenges faced by health care professionals and families in their care. The
      story illustrates how physiologic, sensorimotor, and behavioral issues can all
      impact a child's inability to gain weight as expected. With greater
      understanding, pediatric nurses can appreciate their role as members of a
      multidisciplinary pediatric feeding disorder team.

PMID- 16411542
TI  - The diagnosis and management of cow milk protein intolerance in the primary care
      setting.
AB  - Cow milk protein intolerance (CMPI) affects 3% of infants under the age of 12
      months and is often misdiagnosed as GERD or colic, risking dangerous exposure to
      antigens. Most infants out grow CMPI by 12 months; however, those with IgE
      mediated reactions usually continue to be intolerant to cow's milk proteins and
      also develop other allergens including environmental allergens that cause
      asthmatic symptoms. Clinical manifestations of CMPI include diarrhea, bloody
      stools, vomiting, feeding refusal, eczema, atopic dermatitis, urticaria,
      angioedema, allergic rhinitis, coughing, wheezing, failure to thrive, and
      anaphylaxis. The research and literature showed that CMPI is easily missed in the
      primary care setting and needs to be considered as a cause of infant distress and
      clinical symptoms. This article focuses on correctly diagnosing CMPI and managing
      it in the primary care setting.

PMID- 16411541
TI  - Communicating via expressive arts: the natural medium of self-expression for
      hospitalized children.
AB  - The study was undertaken at a play therapy unit in a Swedish hospital. The
      purpose was directed toward investigating what takes place during play therapy
      when children were given the opportunity to use expressive arts such as clay,
      paint, and/or textile, and the meaning children input into their art objects. The
      study describes an approach to working with hospitalized children when they
      visited the play therapy unit. During a three-year period, hospitalized children
      (n=22) participated in the study. The assumption was that given the opportunity
      to express themselves freely by using a variety of expressive arts, children will
      tell what they express in their art works. It might mirror their thoughts and
      feelings of being hospitalized. The result of the qualitative analyzes generated
      the themes fear, longing, and powerlessness. The results also showed that
      expressive arts were a medium for communication. Expressive arts should be used
      as a tool to help the child express her/himself when being hospitalized.

PMID- 16411543
TI  - Four-year-old with cough and wheeze.

PMID- 16411544
TI  - Search Institute--the organization that helps communities help kids.

PMID- 16411545
TI  - Assessment of child abuse risk factors by advanced practice nurses.
AB  - PURPOSE: To investigate how frequently Advanced Practice Nurses (APN) assess and
      document risk factors for child abuse and neglect (CAN) during family assessments
      and what risk factors are documented. METHOD: APNs were surveyed to determine
      what risk factors are documented in their clinical practice. The survey
      questionnaire was adapted from the Parenting Profile Assessment (PPA) developed
      by Anderson (1987) and included 20 risk factors that are highly predictive of
      parental potential for abusive behavior. Descriptive statistics were used to
      analyze the data, and percentages and frequency distributions were calculated for
      each risk factor. FINDINGS: While 10 of the 20 risk factors were documented on
      over 50% of the time, eight risk factors were documented on less than 40% of
      family assessments. Of the 87 respondents, 63% stated that they have reported one
      or more incidences of suspected child abuse. CONCLUSIONS: These findings
      demonstrate a deficit of knowledge and comprehension of the significance of key
      risk factors for CAN.

PMID- 16411546
TI  - Dissecting an Internet hoax: water, food, plastics, and microwaves.

PMID- 16411547
TI  - HIV risk behaviors and testing rates in adolescent girls: evidence to guide
      clinical practice.

PMID- 16411548
TI  - Models of maternal-infant attachment: a role for nurses.
AB  - Two models of maternal-infant attachment, one related to full-term newborns
      (Goulet, Bell, St-Cyr Tribble, Paul, & Lang, 1998), and one including premature
      infants (Bialoskurski, Cox, & Hayes, 1999), are examined. The elements of both
      models are integrated into a more comprehensive model. Implicit organizational
      components are made explicit, and a discussion regarding the possibility of fit
      for the extremely low-birth-weight (ELBW) group is offered. This integrated model
      can serve as a basis for neonatal nurses to improve care for newly emerging
      families and especially those of the premature/low birth weight group.

PMID- 16411549
TI  - Do you believe a terminal patient should have the right to end his own life?

PMID- 16411552
TI  - Sickle cell crisis! Managing the pain.

PMID- 16411553
TI  - Smart i.v. pumps.

PMID- 16411554
TI  - RSV: protecting the littlest patients.

PMID- 16411555
TI  - Patient Information. What is respiratory syncytial virus (RSV)?

PMID- 16411556
TI  - My battle with a rare disorder.

PMID- 16411557
TI  - A nurse's guide to retirement planning.

PMID- 16411558
TI  - Beyond paternalism.

PMID- 16411559
TI  - Cancer risk assessment: present and future.
AB  - Risk assessment is a process based on available scientific information about
      properties of a given agent, and its effect on biological processes to evaluate
      potential adverse consequences of exposure to that particular agent. Occupational
      cancer risk assessment might be considered as a more specific application of the
      process aimed at finding out whether a particular workplace exposure would lead
      to cancer. In 1983, a comprehensive model or paradigm of risk assessment was
      developed by the US National Academy of Sciences (NAS). The overall risk
      assessment process comprises the following elements: (a) hazard identification,
      which involves the qualitative determination of whether a particular agent causes
      a particular adverse effect in humans; (b) dose-response assessment, which
      describes how such effects are related to the dose; (c) exposure assessment,
      which estimates the level of human exposure to the substance with and/or without
      regulatory controls; (d) risk characterization as summary judgments on the
      existence and magnitude of the public health problem. In this article the authors
      discuss all the elements of the risk assessment process and present current
      approaches to this problem as well as research needs in this area.

PMID- 16411560
TI  - Environmental exposure and birth outcomes.
AB  - The influence of environmental hazards on the health of children is one of the
      major current concerns in environmental health. Scientific investigations are now
      focusing on identifying and understanding the role of environmental hazards in
      the development of birth outcomes that result from in utero exposure to
      environmental contaminants. This paper reviews the published literature with
      provided evidence concerning the impact of environmental exposures to chemicals
      on the incidence of birth outcomes in the areas of environmental pollution
      originating from various sources. In spite of methodological limitations in a
      number of reviewed studies, the present body of knowledge calls for a
      precautionary approach and for preventive measures in order to reduce the risk of
      environmental exposures to chemicals with a recognized or suspected potential to
      cause birth outcomes.

PMID- 16411561
TI  - The role of personal and social resources in preventing adverse health outcomes
      in employees of uniformed professions.
AB  - OBJECTIVES: The purpose of the study was to investigate the impact of experienced
      job stress and personal and social resources (e.g., sense of coherence, self
      esteem, self-efficacy, dispositional optimism and social support) on health
      outcomes in employees of uniformed professions. MATERIALS AND METHODS: A sample
      of 330 men representing uniformed professions (70 policemen, 70 firefighters, 60
      prison officers, 70 security guards and 60 city guards) participated in the
      study. The mean age was 33.99 (SD = 6.44). The Perceived Job Stress
      Questionnaire, the Orientation to Life Questionnaire (SOC-29), Rosenberg's Self
      Esteem Scale, the Generalized Self-Efficacy Scale, the Life Orientation Test, the
      Social Support Scale, and the General Health Questionnaire (GHQ-28) were used in
      the study. RESULTS: The results of the study confirmed a significant role of
      personal and social resources and perceived social support in particular in
      reducing job stress and preventing negative health outcomes in the study group of
      workers of uniformed professions. CONCLUSION: Enhancing personal and social
      resources should be considered in preventive programs aimed at reducing stress in
      the workplace and protecting health of workers of uniformed professions.

PMID- 16411562
TI  - Opinions of Polish occupational medicine physicians on workplace health
      promotion.
AB  - OBJECTIVES: According to the current Polish legislation on occupational health
      services, occupational medicine physicians should perform workplace health
      promotion (WHP) activities as a part of their professional work. The concept of
      workplace health promotion or health promotion programs, however, has not been
      defined in this legislation in any way. Therefore, two essential questions arise.
      First, what is the physicians' attitude towards workplace health issues and
      second, what is actually carried out under the label of health promotion? The
      main objective of the research described in this paper was to answer these
      questions. MATERIALS AND METHODS: The survey was carried out by the National
      Center for Workplace Health Promotion in 2002. A questionnaire prepared by the
      Center for the purpose of this survey was sent to a random sample of occupational
      medicine physicians. RESULTS: The results of the survey showed that 53% of
      occupational medicine physicians consider WHP just as a new name for
      prophylactics. On the other hand almost all of the respondents (94%) agree that
      occupational medicine physicians should perform WHP activities and find them
      useful in improving patients' health (78%). The main obstacle for the development
      of this activity in the perception of physicians is the lack of interest in
      workplace health promotion among employers (86%). CONCLUSIONS: In the modern
      understanding of workplace health promotion concept this type of intervention
      includes not only safety measures and health education, but also a profound
      organizational change that allows employers, employees and social partners to
      improve wellbeing of people at work. Each of such projects should facilitate
      changes necessary to create a health promoting workplace. It also needs a skilled
      leader--well trained and aware of a multidisciplinary dimension of WHP
      interventions. Occupational medicine specialists should become natural partners
      of employers and employees. The majority of the occupational medicine physicians,
      however, are not sufficiently prepared to carry out workplace health promotion
      programs.

PMID- 16411563
TI  - Needlestick injuries in nurses--the Poznan study.
AB  - OBJECTIVES: Needlestick injuries in healthcare workers are common. They are one
      of the main ways of transmitting large numbers of pathogenic micro-organisms in
      healthcare institutions. The aim of this study was to estimate the incidence and
      circumstances of needlestick injuries in a selected population of nurses from the
      city of Poznan and the Wielkopolskie province. MATERIALS AND METHODS: A
      questionnaire was filled in by 232 active nurses with secondary education,
      studying externally at the Medical University in Poznan. The sample was
      representative of nursing specialisations and workplaces of nurses in Poznan and
      the Wielkopolskie province. It comprised of nurses aged 22-51 years (mean, 35
      years) and with work experience of 2-31 years (mean, 13 years). The workplaces of
      the study group were fairly diverse, but the great majority of nurses were
      employed in inpatient care, working in shifts (166 people). RESULTS: The
      probability of needlestick injuries per year equals 28.0%. Accidents of this kind
      were most common among nurses working in surgical wards, operating rooms,
      emergency medical care, GP surgeries and dialysis units. There were significant
      differences in the incidence of needlestick injuries between GP surgeries
      (statistically more common) on the one hand, and surgical wards, non-surgical
      wards and operating rooms on the other. Moreover, accidents in operating rooms
      and surgical wards were significantly more common compared to non-surgical wards.
      Instruments contaminated with infectious material accounted for 73.8% of the
      injuries in the study group of nurses. They were usually injection needles.
      Injuries from sterile needles, clean scalpels and contaminated scalpels were much
      less common. In the vast majority of cases, injuries were self-inflicted, and
      much less frequently caused by patients or colleagues. Most of these accidents
      happened during an attempt to remove a needle from a syringe, and much less while
      trying to place a used needle in a full medical waste container. In almost half
      of the cases (44.9%), the accidents occurred between the second and the fourth
      hour of the shift, which was probably due to a typically heavy workload during
      those hours, particularly on a morning shift. In the great majority of cases
      (84%), the nurses were wearing protective gloves at the time of accidents.
      CONCLUSIONS: The probability of a needlestick injury in the study group per year
      was 28.0%. Accidents of this kind were most common in nurses working in dialysis
      units, emergency medical care, GP surgeries, surgical wards, and operating rooms.
      Occupational sharps injuries were most often caused by a contaminated injection.
      The injuries were self-inflicted in the vast majority of cases. The most common
      cause of injuries from needles was an improper handling of syringes and needles
      after injections (removing a needle from a syringe or placing the needle in a
      full container for medical waste).

PMID- 16411564
TI  - Incidence of asthma in twelve thousand Finnish adults born in 1966.
AB  - OBJECTIVES: Asthma prevalence is increasing in many countries. Some recent
      articles, however, claim that this tendency is drawing to an end. Hence, the
      incidence of persistent asthma was drawn from a birth cohort study in Finland.
      MATERIALS AND METHODS: A cohort of 6107 men and 5839 women was followed from 1981
      to 2004. The participants were members of the Northern Finland Birth Cohort 1966
      Study (NFBC-66). The single-year birth cohort was followed from the age of 15 to
      38 years by means of a complete register held by the national Social Insurance
      Institute (SII) in Finland. Within the register data, an incident case of asthma
      was defined by the received right for reimbursement for asthma medication from
      the SII. RESULTS: Over a 23-year follow-up period, persistent asthma occurred in
      466 study participants of whom 54% were women. The incidence of persistent asthma
      increased from the rate of 10 cases per 10 000 person-years at the age of 15-20
      years to 21 cases per 10 000 person-years at the age of 36-38 years. In females,
      a peak of incidence rate was found between the age of 31 and 35 years, up to 27
      cases per 10 000 person-years. CONCLUSIONS: The follow-up of a population-based
      birth cohort among young working aged Finns shows the increasing incidence rate
      of persistent asthma. In recent years, however, a decline in new cases of asthma
      occurred in females aged between 36 and 38 years.

PMID- 16411565
TI  - Lung function among non-smoking wheat flour mill workers.
AB  - OBJECTIVES: Flour dust occurs across the range of food industries; its exposure
      may induce acute or chronic respiratory ailments. The objective of the study was
      to assess the effects of flour dust on the lung function. MATERIALS AND METHODS:
      The lung function was studied in forty-six male flour mill workers and a similar
      number of male control subjects; all participants were non-smokers with the age
      range from 18 to 65 years. The subjects were matched for age, height, weight and
      socioeconomic status. The pulmonary function test was performed by using an
      electronic spirometer (Compact Vitalograph, UK) and results were compared by a
      paired t-test. RESULTS: Significant reduction in the overall mean values of FVC,
      FEV1, PEF, and MW were observed in wheat flour mill workers relative to their
      matched controls. CONCLUSIONS: Based on the results of the present study, we
      conclude that the flour mill workers in Pakistan, like grain workers elsewhere,
      are at an increased risk of developing occupationally related pulmonary function
      impairments. The results suggest that there is an urgent need to improve dust
      control measures and the health status of flour mill workers.

PMID- 16411567
TI  - The effect of repeated administration of selected benzene bromoderivatives on the
      liver catalase activity in rats.
AB  - OBJECTIVES: Hexabromobenzene (HBB) is used as a flame retardant mainly added to
      plastics, timber and textiles. Tetrabromobenzene (TBB) is its metabolite. Both
      these compounds are present in the environment and in human and animal tissues.
      1,4-Dibromobenzene (1,4-dBB) has found application in agriculture, pharmaceutical
      and some other industries as well as in households. It can also occur in the form
      of an environmental product of HBB debromination. It is known from laboratory
      experiments that animals after repeated exposure to these compounds, show the
      increase in relative liver weight. These results enable us to presume that
      benzene bromoderivatives may prove to be potential peroxisome proliferators.
      MATERIALS AND METHODS: The investigated compounds were administrated
      intragastrically in three different doses for 1, 3, 7, 14, 21 and 28 days.
      Catalase was determined according to the method of Johansson and Borg with use of
      Purpald. RESULTS: Repeated administration of the aforesaid compounds decreased
      catalase activity in the rat liver. CONCLUSIONS: The decreased level of catalase
      may point to its possible inactivation by metabolites of HBB, TBB and 1,4-dBB.

PMID- 16411566
TI  - Neurological and respiratory symptoms in shipyard welders exposed to manganese.
AB  - OBJECTIVE: The nervous system is the major target of the toxic effect of
      manganese (Mn) and its compounds in welding fumes. In humans, inhalation is the
      most frequent route of Mn access, therefore, the respiratory tract and lungs are
      usually involved in the process of translocation of inhaled noxius agent by blood
      to the brain. This study was performed to assess whether it is possible to use
      neurophysiological tests for the detection of early effects of exposure to low Mn
      concentrations. It is also known that irritating welding fumes affect distal
      bronchioles of nonciliated, epithelial Clara cells, which secret anti
      inflammatory and immunossupresive Clara cell protein (CC16) into the respiratory
      tract. The examination of usefulness of CC16 as early pulmonary biomarker for
      neurophysiological abnormal results of welding fumes exposure was performed.
      MATERIALS AND METHODS: The study group comprised 59 welders employed at different
      workposts in a shipyard, matched for age and smoking habits with the control
      group composed of 23 mechanicians and electricians not exposed to welding fumes.
      Subjective neurological symptops (CNS), visual evoked potentials (VEP) and
      electroencephalography (EEG) were examined in welders and the relationships
      between Mn concentrations in the air, blood and urine as well as between
      cummulative exposure index (CEI) (Mn mg/m3 x years of exposure) were
      investigated. Effects of exposure were expressed in the form of biomarkers of the
      body burden, and CC16 as early pulmonary biomarker in welding exposure was
      examined by sensitive latex-immunoassay. RESULTS: Abnormal results of VEP and EEG
      and the lowest CC16 levels were found in the youngest welders exposed to welding
      fumes. Those changes were related to the highest Mn airborne levels (xg > 0.3
      mg/m3) and high blood Mn concentrations (approximately 14.0 microg/dL). The
      highest values of correlation coefficients were found only in welders
      characterized by abnormal neurophysiological results, VEP (r = 0.83) and VEP and
      VEP+EEG (r = 0.82). The multiple linear regression analysis from all analyzed
      subgroups, indicated that those with only abnormal neurophysiological tests, VEP
      and EEG, showed the highest values of partial correlation. It also revealed
      partial correlation cofficiants between Mn in the air, CEI (Mn mg/m3 x years) and
      CC16, Mn-B and Mn-U in VEP and VEP+EEG groups. It was found that the highest
      partial correlations were between the magnitude of exposure--Mn mg/m3, CEI and Mn
      B concentration (R2 = 0.72, R2 = 0.66) as well as between CC16 pulmonary
      biomarker effects and Mn-B concentration (R2 = 0.51). CONCLUSIONS: The
      subclinical effects revealed in neurological endpoints and abnormal results of
      neurophysiological tests, VEP and EEG, confirmed that those sensitive tests could
      be used for the detection of early effect of exposure to low manganese
      concentration. Inhibition of Clara cell protein secretion in younger welders not
      adapted to the Mn environment suppresses anti-inflammatory effect in the
      respiratory tract and probably enhances the absorption and thus the incidence of
      subclinical neurotoxic symptoms related to airborne Mn and Mn-B levels.

PMID- 16411568
TI  - Treatment for the older person. Minimum standards or minimal care.

PMID- 16411569
TI  - Retentive force of O-ring attachment to use Immediate Provisional Implant (IPI)
      retained overdenture.
AB  - This study evaluated the retentive force of the O-ring attachment to an Immediate
      Provisional Implant (IPI)-retained overdenture. Two sizes of O-rings (#1, #2)
      were placed on the IPI abutment head. As the controls, soft relining material,
      silicone lining material, and the PMMA resin were used to connect the IPI
      abutment head. The retentive forces (n=5, N) obtained at a crosshead speed of 40
      mm/min were analyzed by ANOVA/Tukey's HSD test (alpha=0.05). O-ring #1 showed the
      significantly greatest force among all materials tested (p0.05). Appropriate
      retention was obtained using the smaller O-ring#1 for the IPI-retained
      overdenture.

PMID- 16411570
TI  - Adverse reaction to prophylactic amoxicillin: a case report.
AB  - Antibiotic prophylaxis is required prior to invasive dental procedures for those
      patients at risk of bacterial endocarditis. The clinician should be aware of the
      possibility of allergic reaction to the antibiotics and be prepared for the
      medical management of the symptoms. This paper presents a case of an allergic
      reaction to prophylactic amoxicillin administered orally to a patient prior to
      dental treatment.

PMID- 16411571
TI  - Effect of screw hole filling on retention of implant crowns.
AB  - The screw access channels of 15 degrees angled Esthetic Abutments (Branemark
      System) were either (a) completely filled with a vinyl polysiloxane impression
      material (Memosil), (b) partially filled with Memosil or (c) had lower portion
      filled with Memosil and the remainder with composite resin. The force required to
      remove a temporarily cemented restoration was measured. The removal force was
      significantly reduced with the channel completely filled with Memosil compared to
      those partially filled with Memosil (p<0.01) or with composite resin placed over
      Memosil (p<0.01). The method selected to fill the screw access channel of an
      implant abutment can be a significant factor affecting retention of a cemented
      restoration.

PMID- 16411572
TI  - Dimensional change of heat-cured acrylic resin dentures with three different
      cooling regimes following a standard curing cycle.
AB  - The aim of the study was to compare dimensional changes in
      poly(methylmethacrylate) complete denture bases resulting from three different
      cooling regimens following a standard heating cycle. Changes in three separate
      dimensions were measured on ten dentures within each cooling regimen after
      curing, and before and after removing the denture from the cast using a computer
      imaging system. No consistent differences occurred as a result of removing the
      denture from the cast. The results indicated that there was greater change in
      dimension of dentures with the quenching cooling method than with either
      overnight cooling in the water bath or bench cooling. This was particularly
      evident after removal from the cast after curing (p<0.001). It is concluded that
      slow cooling results in less dimensional change.

PMID- 16411573
TI  - Effect of investment material and water immersion time on tooth movement in
      complete denture.
AB  - This study verified the effect of the association gypsum or silicone investment
      support materials and water immersion on the relative tooth movement in complete
      dentures. Wax record bases with teeth were assigned to 2 groups (n=10): 1--type
      III dental stone (control), and 2--condensation silicone. Linear distances (mm)
      between teeth were recorded after deflasking and after water storage for 1 week,
      1 month and 3 months. With the exception of the silicone for the pre-molar
      distance after water storage for 3 months, the association between the type of
      investment and period of water storage did not alter the distances between teeth.

PMID- 16411574
TI  - Mandibular displacement related to simulated loss of posterior occlusal support.
AB  - Mandibular displacement related to simulated loss of posterior occlusal support
      was investigated. Twenty-four volunteers with natural dentitions were selected.
      To change the posterior occlusal support, occlusal splints fitted to maxillary
      dental arches were cut in sequence from the most posterior to anterior. The more
      the absence of posterior occlusal support increased, the more both condylar
      displacements were increased (R: 0.97mm, L: 0.94mm). Moreover, subjects could be
      divided into two groups depending upon their condylar mobility following with
      reduced occlusal support. These results suggest that individual adaptability to
      the imbalanced occlusal condition should be always considered.

PMID- 16411575
TI  - Early surface microhardness of a resin composite exposed to a pulse-delayed
      curing exposure: a comparison of a tungsten halogen and a plasma arc lamp, in
      vitro.
AB  - Surface microhardness numbers of a commercial resin composite have been compared
      after exposure to a quartz tungsten halogen (QTH) and plasma arc (PAC) lamp
      respectively, using two exposure protocols. The effect of increased tip-to
      composite distance has also been compared. Exposure with the PAC lamp tested is
      more appropriate to the early finishing of composite restorations after placement
      and curing than with the QTH. However both lamps were capable of producing
      comparable surface hardness, with appropriate exposure protocols. The effect of
      increased tip-to-composite distance was generally not significant between the
      lamps for continuous exposure.

PMID- 16411576
TI  - The need for dental treatment in a group of patients undergoing treatment for
      malignancies other than of the head and neck.
AB  - This paper reports the findings of an audit carried out to estimate the dental
      needs of patients undergoing oncology therapy for malignant disease at various
      sites of the body. All of the subjects were in-patients on an oncology ward. Over
      fifty percent of the patients had dental, periodontal or mucosal disease. It was
      concluded that there is a need to increase the dental service provided to cancer
      patients to allow further co-ordination between medical, dental and nursing staff
      for the prevention, management and resolution of oral complications of cancer
      therapy.

PMID- 16411577
TI  - The acidic and erosive potential of five sports drinks.
AB  - Sports drinks are becoming increasingly popular as we are all being encouraged to
      adopt a healthier lifestyle with regular exercise. However, many of these
      products are based on acidic fruits and may contribute to erosion. The aim of
      this study was to screen a number of these products for their potential to cause
      enamel erosion in vitro. The erosive potential of a number of readily available
      sports drinks was assessed in the laboratory by measuring their pH, neutralisable
      acidity and their ability to erode enamel. These were compared to a positive
      control, orange juice and a negative control, water. The pH of the sports drinks
      ranged from 3.16-3.70 with their neutralisable acidity ranging from 9.74-13.44
      mls of 0.1M NaOH. The amount of enamel removed following 1-hour immersion in the
      sports drinks ranged from 1.18-5.36 microns. In comparison, the orange juice
      control had a pH of 3.68, a neutralisable acidity of 19.68 mls of 0.1 M NaOH and
      removed 3.24 microns of enamel. Many of the sports drinks tested were found to be
      erosive. This information will be of use to clinicians when counselling patients
      with tooth surface loss who use fruit based sports drinks regularly.

PMID- 16411578
TI  - The importance of assessing pain in horses and donkeys.

PMID- 16411579
TI  - A graphic framework for teaching critical appraisal of randomised controlled
      trials.
AB  - Students of evidence-based medicine often try unsuccessfully to commit to memory
      a particular critical appraisal framework (often lengthy), or they have to depend
      on pocket cards and are lost without them. We have described a pedagogic aid: a
      flow diagram of an RCT, which has been developed over years of teaching
      residents. This diagram focuses on the steps in an RCT, and by drawing arrows, it
      highlights the biases possible at each step. This diagram serves as a framework
      on which the list of critical appraisal questions can be hung and is easy to
      remember.

PMID- 16411580
TI  - Arthroscopic diagnosis and treatment of intra-articular insertional injuries of
      the suspensory ligament branches in 18 horses.
AB  - REASONS FOR PERFORMING STUDY: Clinical association between the branches of
      insertion of the suspensory ligament (SL) and metacarpophalangeal (MCP) and
      metatarsophalangeal (MTP) joints has been reported. However, there has been no
      assessment of the lengths of the SL branches which are subsynovial with respect
      to the joints or reports of involvement of the MCP/MTP joints in injuries of the
      SL branches. OBJECTIVES: To establish proportions of SL branches subsynovial with
      respect to the MCP/MTP joints and report clinical and arthroscopic findings in
      horses with desmitis of SL branches identified as having an articular component
      to the lesion. HYPOTHESIS: Arthroscopic surgery enables identification and
      potential treatment of intra-articular injuries of SL branches. METHODS: Twelve
      forelimbs and 13 hindlimbs were dissected and the total and subsynovial lengths
      of the SL branches recorded. Case records of horses with intra-articular injuries
      of the SL branches were reviewed and 18 animals identified. Diagnostic
      information and arthroscopic findings were recorded and results of treatment
      determined by telephone follow-up. RESULTS: Of SL branches, 28.45% in the
      forelimb and 29.56% in the hindlimb were subsynovial to the MCP and MTP joints.
      All animals with intra-articular lesions of the SL branch were lame and had
      distension of the affected MCP/MTP joint. In 16 horses (17/22 branches), there
      was palpable thickening of the affected SL branch. Disrupted infrastructure was
      evident ultrasonographically in 15/17 branches and involvement of the dorsal
      articular surface of the ligament was predicted in 12/17 branches. Following
      arthroscopic intervention, 13 horses returned to work at a level equal to or
      greater than that achieved prior to injury and 2 returned to work at a lower
      level. Three horses incurred separate injuries and were retired or subjected to
      euthanasia. CONCLUSIONS: Articular involvement should be considered in animals
      with injuries of an SL branch and concurrent distension of the MCP/MTP joint.
      Arthroscopy is necessary to identify such lesions confidently and to direct case
      management. POTENTIAL RELEVANCE: Arthroscopy of the MCP/MTP joints can make a
      positive contribution to the assessment and management of some SL branch
      injuries.

PMID- 16411581
TI  - Histopathology in horses with chronic palmar foot pain and age-matched controls.
      Part 1: Navicular bone and related structures.
AB  - REASONS FOR PERFORMING STUDY: Causes of palmar foot pain and the
      aetiopathogenesis of navicular disease remain poorly understood, despite the high
      incidence of foot-related lameness. HYPOTHESES: Abnormalities of the collateral
      sesamoidean ligaments (CSLs), distal sesamoidean impar ligament (DSIL), deep
      digital flexor tendon (DDFT), navicular bone, navicular bursa, distal
      interphalangeal (DIP) joint or collateral ligaments (CLs) of the DIP joint may
      contribute to palmar foot pain. METHODS: Feet were selected from horses with a
      history of unilateral or bilateral forelimb lameness of at least 2 months'
      duration that was improved by perineural analgesia of the palmar digital nerves,
      immediately proximal to the cartilages of the foot (Group 1, n = 32); or from age
      matched control horses (Group 2, n = 19) that were humanely destroyed for other
      reasons and had no history of forelimb foot pain. Eight units of tissue were
      collected for histology: the palmar half of the articular surface of the distal
      phalanx, including the insertions of the DDFT and DSIL; navicular bone and
      insertion of the CSLs; DDFT from the level of the proximal interphalangeal (PIP)
      joint to 5 mm proximal to its insertion; synovial membrane from the palmar pouch
      of the DIP joint and the navicular bursa; CLs of the DIP joint and DSIL. The
      severity of histological lesions for each site were graded. Results were compared
      between Groups 1 and 2. RESULTS: There was no relationship between age and grade
      of histological abnormality. There were significant histological differences
      between groups for lesions of the flexor aspect, proximal and distal borders, and
      medulla of the navicular bone; the DSIL and its insertion and the navicular
      bursa; but not for lesions of the CSLs, the dorsal aspect of the navicular bone,
      distal phalanx and articular cartilage, synovium or CLs of the DIP joint.
      CONCLUSIONS: Pathological abnormalities in lame horses often involved not only
      the navicular bone, but also the DSIL and navicular bursa. Abnormalities of the
      navicular bone medulla were generally only seen dorsal to lesions of the FFC.
      POTENTIAL RELEVANCE: Adaptive and reactive change may be occurring in the
      navicular apparatus in all horses to variable degrees and determination of the
      pathogenesis of lesions that lead to pain and biomechanical dysfunction should
      assist specific preventative or treatment protocols.

PMID- 16411582
TI  - Histopathology in horses with chronic palmar foot pain and age-matched controls.
      Part 2: The deep digital flexor tendon.
AB  - REASONS FOR PERFORMING STUDY: Causes of palmar foot pain and the
      aetiopathogenesis of navicular disease remain poorly understood, despite the high
      incidence of foot-related lameness. HYPOTHESES: Abnormalities of the deep digital
      flexor tendon (DDFT) may contribute to palmar foot pain; ageing degenerative
      changes may be seen in horses free from lameness; and horses with lameness are
      likely to have a greater severity of abnormalities than age-matched horses with
      no history of foot pain. METHODS: Feet were selected from horses with a history
      of uni- or bilateral forelimb lameness of at least 2 months' duration. Histology
      of the DDFT from the level of the proximal interphalangeal joint to its insertion
      were examined and the severity of lesions for each site graded. Associations
      between lesions of the navicular bone, collateral sesamoidean ligaments (CSL),
      distal sesamoidean impar ligament, navicular bursa, distal interphalangeal (DIP)
      joint synovium and collateral ligaments of the DIP joint and DDFT were assessed.
      RESULTS: There was no relationship between age and grade of histological
      abnormality of the DDFT. There were significant histological differences between
      groups for lesions of the dorsal layers of the DDFT, but not for lesions of the
      palmar aspect. There were significant associations between histological grades
      for the superficial dorsal layer of the DDFT and flexor aspect of the navicular
      bone; and between the deep dorsal layer of the DDFT and the proximal border and
      medulla of the navicular bone. The navicular bursa grade was correlated with
      grades for the superficial dorsal, deep dorsal and deep palmar layers of the
      DDFT. The histological grades for the CSL and the superficial dorsal layer of the
      DDFT were also associated. CONCLUSIONS: Pathological abnormalities in lame horses
      often involved the DDFT in addition to the navicular bone. Vascular and matrix
      changes may precede changes in the fibrocartilage of the navicular bone.
      POTENTIAL RELEVANCE: Identification of factors leading to vascular changes within
      the interstitium of the DDFT and changes in matrix composition, may help in
      future management of palmar foot pain.

PMID- 16411584
TI  - The complex blood supply to the equine testis as a cause of failure in
      laparoscopic castration.
AB  - REASONS FOR PERFORMING STUDY: Intra-abdominal ligation/ transection of the
      spermatic cord may result in necrosis of the testis; castration of abdominal
      cryptorchids via laparoscopy has therefore become common. Notwithstanding some
      adaptations of the technique, a small percentage of operations fail, prompting
      research into the anatomical background and clinical relevance of the procedure.
      HYPOTHESIS: That an alternate blood supply may prevent complete necrosis of the
      testis after spermatic cord transection. OBJECTIVE: To establish the prevalence
      of the problem in normal and cryptorchid stallions. METHODS: In a preliminary
      study, the spermatic cords of 8 normal stallions were ligated and transected at
      different sites and in various manners. Five weeks later the testes were removed
      and the vitality of both the testes and epididymes was evaluated. In a
      prospective clinical trial, intra-abdominal spermatic cord transection was
      performed in 241 cryptorchid and normal stallions. In cases of surgical failure,
      the testes were removed and histology performed. RESULTS: Examination of the
      specimen removed from the 8 animals of the preliminary study revealed that all
      epididymes were completely or largely spared. All except one testis were
      completely necrotic. In the patients that underwent surgery all abdominally
      retained testes (n = 123) were necrotic, while 5 out of 88 inguinally retained
      and 8 out of 236 normally descended testes had partially survived. The pattern of
      survival differed between inguinally retained and normally descended testes. The
      epididymes of these 13 horses were (largely) vital. The (partial) survival of the
      epididymes and inguinally retained testes was ascribed to an alternate blood
      supply via anastomosing vessels derived from the cremasteric artery. A tributary
      from the external pudendal artery was considered responsible for the partial
      survival of normally descended testes. CONCLUSIONS AND POTENTIAL RELEVANCE: After
      intra-abdominal transection of the entire spermatic cord, 5.6% of inguinally
      retained and 3.4% of normally descended testes failed to become completely
      necrotic, as a result of an alternate blood supply via the cremasteric and/or
      external pudendal artery. Therefore, laparoscopic castration without orchidectomy
      cannot be recommended as a trustworthy method for castration of inguinal
      cryptorchids and normal stallions.

PMID- 16411583
TI  - Results of plate fixation of type 5 olecranon fractures in 20 horses.
AB  - REASONS FOR PERFORMING STUDY: Previous olecranon fracture reports contain a small
      proportion of type 5 fractures, mostly treated with conservative therapy.
      OBJECTIVES: To evaluate the clinical details and outcome of type 5 olecranon
      fractures in a large group of horses treated by tension band plate fixation and
      to compare results with other treatment methods. METHODS: Medical records of 97
      cases, including 32 (33%) classified as type 5, were reviewed. Subject details,
      history, radiographic findings, treatment and follow-up results (2-146 months
      post operatively) were recorded. RESULTS: Treatment included open reduction and
      internal fixation using a narrow or broad dynamic compression plate (n = 20),
      conservative therapy (n = 7) and euthanasia (n = 5). Long-term follow-up was
      available in 15 cases treated surgically, of which 2 were sound and in training,
      11 sound and performing athletically and 2 unsound. Distal semilunar notch
      involvement, comminution or open status did not appear to affect prognosis.
      CONCLUSIONS: Internal plate fixation provides an excellent prognosis for an
      animal to be capable of athletic performance. POTENTIAL RELEVANCE: Describing
      tension band plate fixation and results offers a method of fracture repair that
      should improve treatment and prognosis for type 5 olecranon fractures.

PMID- 16411585
TI  - Evaluation of an in vitro sulphidoleukotriene release test for diagnosis of
      insect bite hypersensitivity in horses.
AB  - REASONS FOR PERFORMING STUDY: Insect bite hypersensitivity (IBH) is an IgE
      mediated allergic dermatitis caused by bites of Culicoides and Simulium species,
      and improved means of diagnosis are required. OBJECTIVES: The cellular antigen
      simulation test (CAST) with C. nubeculosus and S. vittatum extracts was assessed
      in a population of IBH-affected and healthy horses. Variations in test results
      over a one year period and possible cross-reactivity between different insect
      extracts was studied. METHODS: A total of 314 mature horses were studied using
      the CAST. Influence of severity of clinical signs, gender and age were evaluated,
      and 32 horses were tested repeatedly over one year. The kappa reliability test
      was used to assess agreement of the test results with different insect extracts.
      RESULTS: Horses with IBH had significantly higher sLT release than controls with
      C. nubeculosus and S. vittatum. The highest diagnostic sensitivity and
      specificity levels were attained when using adult C. nubeculosus extracts with
      the CAST (78% and 97%, respectively), suggesting that most horses with IBH are
      sensitised against Culicoides allergens. A proportion of IBH-affected horses was
      found to be sensitised to allergens of Simulium spp. in addition to those of C.
      nubeculosus. The CAST with C. nubeculosus had positive and negative predictive
      values > or = 80% for a true prevalence of IBH of 12-52%. In the follow-up study,
      the proportion of IBH-affected horses with a positive test result ranged from 90%
      in November to 68% in March. Severity of clinical signs or age did not influence
      test results significantly. However, IBH-affected males achieved significantly
      more positive test results than IBH-affected females. CONCLUSIONS: The CAST with
      adult C. nubeculosus has high specificity and good sensitivity for diagnosis of
      IBH. Horses with IBH are mainly sensitised to Culicoides allergens, and some
      horses are additionally also sensitised to allergens in Simulium spp. POTENTIAL
      RELEVANCE: The CAST is likely to be a useful test for diagnosis of IBH, even
      allowing the identification of IBH-affected but asymptomatic horses. This test
      may also help in further characterisation of allergens involved in this
      condition.

PMID- 16411586
TI  - Horses on pasture may be affected by equine motor neuron disease.
AB  - REASONS FOR PERFORMING STUDY: Equine motor neuron disease (EMND) was diagnosed in
      3 horses maintained on lush, grass-based pasture. This contrasted with North
      American studies which identified limited or no access to green herbage as an
      important risk factor for EMND. HYPOTHESIS: Grazing horses that have an
      apparently adequate intake of pasture herbage to meet normal equine vitamin E
      requirements can develop EMND. METHODS: Owners of 32 European horses diagnosed
      with EMND completed a questionnaire regarding intrinsic, managemental,
      nutritional and environmental factors that could potentially be risk factors for
      EMND, and also regarding clinical signs, treatments and case outcome.
      Plasma/serum vitamin E data for these horses were supplied by the veterinarians.
      No control population was studied. RESULTS: Thirteen of 32 horses (termed the
      'grazing' group) had part- or full-time access to grass-based pasture at the
      onset of EMND (median duration at pasture 12 h/day, range 3-24 h). Five of these
      horses were at pasture for at least 235 h/day at the onset of EMND, 2 of which
      were at pasture for at least 23.5 h/day throughout the year. Despite grazing, all
      these horses had a low vitamin E status. The remaining 19 horses resembled those
      cases reported from North America, in that they had no or limited access to
      pasture. CONCLUSIONS AND POTENTIAL RELEVANCE: A diagnosis of EMND should not be
      discounted on the basis that a horse has access, even full-time, to lush grass
      based pasture. Inadequate vitamin E intake was probably not the sole cause of
      either the EMND or the low vitamin E status in the grazing horses; the latter was
      probably the result of abnormal bioavailability or excessive utilisation of
      vitamin E.

PMID- 16411587
TI  - Qualitative and quantitative evaluation of equine respiratory mechanics by
      impulse oscillometry.
AB  - REASONS FOR PERFORMING STUDY: The long-established conventional reference
      technique (CRT) for measuring respiratory mechanics in horses lacks sensitivity
      and there is a need for further refinement in new technology, such as the impulse
      oscillometry system (IOS). OBJECTIVES: To evaluate the potential use of the IOS
      as a clinical respiratory function test and compare it to the current CRT in
      horses suffering from common upper and lower airway dysfunctions. METHODS: Six
      healthy horses were tested before and after induction of a unilateral nasal
      obstruction (UNO) or transient left laryngeal hemiplegia (LLH). Six heaves
      affected horses were tested in clinical remission and during a heaves crisis,
      before and after nebulisation of cumulative doses of a bronchodilator therapy
      (ipratropium bromide; IPB). RESULTS: As opposed to the CRT, the IOS was able to
      detect partial upper airway obstruction (UAO) caused by UNO or LLH in resting
      horses, without differentiating both conditions. Upper airway obstruction caused
      an upward shift of resistance (R(rs)) from 5 to 35 Hz without altering reactance
      (X(rs)). As for the CRT, IOS respiratory parameters measured in heaves-affected
      horses in crisis differed significantly from values measured during remission.
      The difference in frequency-dependent behaviour of R(rs) and X(rs) allowed
      discrimination between upper and lower airway obstructions. Bronchodilator
      treatment induced significant dose-dependent changes in X(rs) at 5 and 10 Hz,
      from the first dose. Total pulmonary resistance (RL) and R(rs) at 5 Hz were
      affected from the second dose and displayed similar sensitivity. Although post
      treatment RL values were comparable to remission, R(rs) and X(rs) remained
      significantly different, characterising persistent peripheral obstruction.
      CONCLUSIONS: The IOS was more sensitive than the CRT in detecting partial UAO in
      resting horses and persistent post treatment peripheral dysfunction in heaves
      affected horses. The IOS is a sensitive test that provides graded quantitative
      and qualitative information on disease-induced respiratory dysfunctions as well
      as on treatment efficiency in horses. POTENTIAL RELEVANCE: The IOS could
      represent a practical and sensitive alternative respiratory function test for
      routine clinical investigations of common airway obstructive diseases and therapy
      in horses.

PMID- 16411588
TI  - Evaluation of a nested PCR test and bacterial culture of swabs from the nasal
      passages and from abscesses in relation to diagnosis of Streptococcus equi
      infection (strangles).
AB  - REASONS FOR PERFORMING STUDY: Streptococcus equi is the cause of strangles in
      horses. To improve diagnostic sensitivity, development and evaluation of DNA
      based methods are necessary. OBJECTIVES: To evaluate diagnostic methods and
      observe the pattern of bacterial shedding during natural outbreaks. METHODS: Two
      herds with natural outbreaks of strangles were visited over a period of 15 weeks
      and 323 samples originating from 35 horses investigated. The diagnostic use of a
      nested PCR test was evaluated using a collection of 165 isolates of Lancefield
      group C streptococci (species specificity) and swabs from nasal passages or from
      abscesses from horses infected with S. equi (diagnostic sensitivity). RESULTS:
      All 45 S. equi isolates tested positive in the nested PCR, whereas no amplicon
      was formed when testing the other 120 Lancefield group C isolates. A total of 43
      samples were collected from 11 horses showing clinical signs of strangles during
      the study period. The diagnostic sensitivity for PCR test was 45% and 80% for
      samples from the nasal passages and abscesses, respectively; the corresponding
      diagnostic sensitivity for cultivation was 18% and 20%. The diagnostic
      sensitivity was significantly higher for PCR than for bacterial cultivation.
      Furthermore, the shedding of S. equi in 2 infected horse populations was
      evaluated. An intermittent shedding period of S. equi of up to 15 weeks was
      recorded in this part of the study. It was also shown that shedding of S. equi
      occurred both from horses with and without clinical signs. CONCLUSIONS AND
      POTENTIAL RELEVANCE: The nested PCR test represents a species-specific and 
      sensitive method for diagnosis of S. equi from clinical samples. It may, however,
      be desirable in future to develop detection methods with high diagnostic
      sensitivity and specificity without the potential problems inherent in nested
      PCR.

PMID- 16411589
TI  - Effect of local analgesia on movement of the equine back.
AB  - REASONS FOR PERFORMING STUDY: Diagnostic infiltration of local anaesthetic
      solution is commonly used in cases of equine back pain. Evaluation is subjective
      and it is not known how local analgesia of the back affects horses without
      clinical signs of back pain. OBJECTIVES: To evaluate the effect of infiltration
      of local anaesthetics on the movement of the back in horses without clinical
      signs of back pain, and to evaluate the usefulness of kinematic studies as an
      objective and quantitative tool in evaluating local analgesia in clinical
      practice. METHODS: The kinematics of the back in 10 clinically sound horses were
      measured on 2 occasions at walk and trot before and after injections with
      mepivacaine and sodium chloride around the interspinous spaces between T16 and
      L2. The kinematics were compared between the 2 occasions before injections and
      before and after each injection. RESULTS: The range of motion (ROM) for
      dorsoventral flexion-extension (FE) of the back was increased significantly in
      all measured segments other than T10 at walk, as was lateral bending (LB) at T10,
      L3 and L5 after injection of mepivacaine. For lateral excursion (LE), total
      movement increased at all measured segments. At trot the only affected segment
      was L3, where the injection with mepivacaine decreased the ROM for FE. After
      injection of sodium chloride the ROM for FE increased at T13 and T17 at walk.
      Lateral bending and LE were not affected at walk. At trot, LB increased at L3 and
      L5. CONCLUSIONS AND POTENTIAL RELEVANCE: Diagnostic infiltration of local
      anaesthetic solution affects the function of the back in clinically sound horses,
      which must be considered when interpreting the use of this clinical aid in
      assessing clinical cases of back dysfunction. Kinematics can qualitatively and
      quantitatively evaluate the effect of local analgesia of the back.

PMID- 16411590
TI  - Mechanical nociceptive thresholds in the axial skeleton of horses.
AB  - REASONS FOR PERFORMING STUDY: An objective measure of neck, back and croup pain
      is needed in horses with musculoskeletal injuries, vague upper limb lameness or
      poor performance. OBJECTIVES: To establish mechanical nociceptive thresholds
      (MNTs) within the axial skeleton and evaluate the effects of subject status and
      ridden exercise. METHODS: Thirty-six mature horses (10 nonridden; 26 actively
      ridden) were used to assess MNTs evoked by a pressure algometer (PA) with a 1 cm2
      rubber plunger tip at 62 midline and bilaterally symmetrical anatomical landmarks
      along the axial skeleton. Pressure was applied at a uniform rate of application
      until a local avoidance reaction was noted. The repeatability of 3 consecutive
      measurements was evaluated. Left-to-right comparisons and the effects of subject
      status and ridden exercise on MNTs were assessed. RESULTS: MNTs were repeatable
      and increased in a cranial-to-caudal gradient within the axial skeleton.
      Typically, there were no significant left-to-right differences. Within-horse
      variability was less than between-horse variability. Higher MNTs were measured in
      young, heavy, non-Thoroughbred, castrated males, and in horses that were ridden
      and actively exercised. CONCLUSIONS AND POTENTIAL RELEVANCE: PA provides an
      objective, noninvasive, and repeatable tool to measure mechanical nociception in
      horses. MNTs vary in horses with differing subject status and ridden exercise
      level.

PMID- 16411591
TI  - Pressure algometry for the detection of induced back pain in horses: a
      preliminary study.
AB  - REASONS FOR PERFORMING STUDY: Pressure algometry (PA) is a potential modality for
      objectively measuring mechanical nociceptive thresholds (MNTs) in horses. Its
      ability to differentiate musculoskeletal pain sites from nonpain sites is unknown
      and must be assessed prior to its clinical application. OBJECTIVES: To assess the
      ability of PA to detect induced musculoskeletal pain. METHODS: Twenty clinically
      normal mature horses (2 groups of 10 horses, over 2 years) were used to measure
      MNTs before and after implantation and removal of 2 fixation half-pins in the
      dorsal spinous processes of 2 adjacent vertebrae. To assess hyperalgesia, MNTs
      near the surgical sites were pooled and compared to surrounding landmarks. MNTs
      were also compared on 2 consecutive days immediately after surgical implantation.
      To assess longer-term adaptation or sensitisation, changes from the beginning to
      the end of the study were evaluated. RESULTS: The precise surgical sites could be
      recognised due to substantial and localised decreases in the MNTs compared with
      surrounding landmarks. At most sites distant to the surgical sites, the
      distribution of the median percentage change in MNTs was centred around 0
      (suggesting unbiased repeatability). MNTs compared from the beginning to the end
      of this study did not demonstrate obvious adaptation or sensitisation.
      CONCLUSIONS AND POTENTIAL RELEVANCE: PA provides a quantitative and repeatable
      method for assessing the presence of musculoskeletal pain. Further studies are
      needed to evaluate PA clinically for assessing musculoskeletal injuries and pain
      management strategies in horses.

PMID- 16411592
TI  - Navicular disease: a review of what's new.

PMID- 16411593
TI  - Tetracycline therapy of Lawsonia intracellularis enteropathy in foals.

PMID- 16411594
TI  - Evaluation of glucosamine levels in commercial equine oral supplements for
      joints.

PMID- 16411595
TI  - Dendrimers for pharmaceutical and biomedical applications.
AB  - Dendrimers are a unique class of synthetic macromolecules having a highly
      branched, three-dimensional, nanoscale architecture with very low polydispersity
      and high functionality. Structural advantages allow dendrimers to play an
      important role in the fields of nanotechnology, pharmaceutical and medicinal
      chemistry. This review discusses several aspects of dendrimers, including
      preparation, dendrimer-drug coupling chemistry, structural models of dendrimer
      based drug delivery systems, and physicochemical and toxicological properties.

PMID- 16411596
TI  - Nanotube-doped alginate gel as a novel carrier for BSA immobilization.
AB  - In this paper different dopants, including carbon nanotubes (CNTs), silica
      nanotubes (SiNTs), graphite and silica gel, were incorporated into alginate (ALG)
      gel to form nanotube/alginate or nanoparticle/alginate composites used for bovine
      serum albumin (BSA) immobilization carrier. During encapsulation, first BSA was
      adsorbed on the dopants, and then BSA and dopants were suspended in alginate
      solution, followed by being added dropwise into the CaCl2 solution to form the
      biocomposites. The BSA leakage decreased significantly in these biocomposites as
      the following order: BSA-ALG-SiNT > BSA-ALG-CNT > BSA-ALG-SiO2 > BSA-ALG
      graphite, which was mainly due to firstly the protein molecule adsorption on the
      dopants which could not be washed out easily and secondly, during the
      biocomposites formation, water loss in BSA-ALG-dopant biocomposites became less
      than that in BSA-ALG biocomposite. In addition, the mechanical properties of
      these biocomposites were remarkably reinforced in the same order as BSA leakage
      decrease.

PMID- 16411597
TI  - Endothelial cell function on 2D and 3D micro-fabricated polymer scaffolds:
      applications in cardiovascular tissue engineering.
AB  - Polymeric structures of a polylactide-polycaprolactone blend were micro
      fabricated using the Pressure Assisted Microsyringe (PAM) system. Human umbilical
      vein endothelial cells were cultured on the scaffolds, and apoptosis, cell
      adhesion, proliferation and metabolism were evaluated. In addition, more specific
      indicators of endothelial cell function, namely nitric oxide and endothelin
      production, were also assessed. Thin films of the blend, as well as gelatine
      coated glass slides (as controls) were used. The results show that as far as
      adhesion, apoptosis and metabolism are concerned, the scaffolds do not interfere
      with cell function compared with gelatin controls. However, the nitric
      oxide/endothelin ratio was higher than that observed on the gelatin films,
      suggesting that the scaffolds could be used for engineering small diameter blood
      vessels without risk of occlusion.

PMID- 16411598
TI  - A time-temperature rheological study of konjac glucomannan hydrocolloid.
AB  - Konjac glucomannan (KGM) is one of the most versatile soluble biomaterials having
      wide-ranging applications. The shear storage, G', and loss, G", moduli of this
      hydrocolloid were recorded as functions of angular frequency varying from 0.1 to
      100.0 rad/s and temperature from 5 to 50 degrees C. It was found that both G' and
      G" mainly increase with angular frequency in the range from 0.1 to 100 rad/s. As
      the temperature increases from 5 to 95 degrees C, the values of G' and G"
      decrease. A novel criterion for the thermorheologically simple material, and a
      procedure to calculate the shift factor from the angular frequency sweep and
      temperature ramp data were presented. By these methods, the KGM hydrocolloid is
      found to obey the TTS principle as log G" and log G' are less than 1.529 and
      1.436, respectively. The Williams-Landel-Ferry equation can describe the shift
      factor of the KGM hydrocolloid.

PMID- 16411599
TI  - The impact of vacuum freeze-drying on collagen sponges after gas plasma
      sterilization.
AB  - The sterilization of porous collagen sponges remains a challenging procedure.
      Gamma irradiation denatures collagen, resulting in dramatic changes to its
      structure. Ethylene oxide leaves toxic residues requiring weeks to evaporate.
      This study investigated the impact on cell behavior of gas plasma treatment when
      combined with vacuum freeze-drying. The goal of this procedure is to eliminate
      the molecules of hydrogen peroxide remaining after the sterilization process,
      together with their decomposition products, from the scaffolds. These molecules
      hinder the immediate use of the porous designs. Collagen and EDC/NHS-heparinized
      collagen scaffolds were sterilized with gas plasma. H2O2 released by the collagen
      specimens was measured by peroxidase test both immediately and also 1 week after
      the plasma treatment. Further measurements were done 24, 36, 48 and 72 h after
      vacuum freeze-drying. The activity of these scaffolds was further evaluated in
      relation to the proliferation, migration and differentiation of human umbilical
      vein endothelial cells (HUVECs). Both immediately after exposure to gas plasma
      and also 1 week later, the collagen designs contained significantly higher
      concentrations of H2O2 than scaffolds having also undergone vacuum freeze-drying.
      This procedure achieved faster decontamination of the remaining H2O2. Following
      vacuum freeze-drying, sponges already allowed HUVEC proliferation after 48 h, but
      in non-lyophilized specimens after gas plasma treatment alone, cell death
      occurred as early as only 1 week later. These data highlight the advantages of
      carrying out vacuum freeze-drying following gas plasma sterilization. The results
      show the substantial impact of sterilization of porous materials made for tissue
      engineering.

PMID- 16411600
TI  - Electrospinning versus knitting: two scaffolds for tissue engineering of the
      aortic valve.
AB  - Two types of scaffolds were developed for tissue engineering of the aortic valve;
      an electrospun valvular scaffold and a knitted valvular scaffold. These scaffolds
      were compared in a physiologic flow system and in a tissue-engineering process.
      In fibrin gel enclosed human myofibroblasts were seeded onto both types of
      scaffolds and cultured for 23 days under continuous medium perfusion. Tissue
      formation was evaluated by confocal laser scanning microscopy, histology and DNA
      quantification. Collagen formation was quantified by a hydroxyproline assay. When
      subjected to physiologic flow, the spun scaffold tore within 6 h, whereas the
      knitted scaffold remained intact. Cells proliferated well on both types of
      scaffolds, although the cellular penetration into the spun scaffold was poor.
      Collagen production, normalized to DNA content, was not significantly different
      for the two types of scaffolds, but seeding efficiency was higher for the spun
      scaffold, because it acted as a cell impermeable filter. The knitted tissue
      constructs showed complete cellular in-growth into the pores. An optimal scaffold
      seems to be a combination of the strength of the knitted structure and the cell
      filtering ability of the spun structure.

PMID- 16411601
TI  - Immobilization of aminoglycosidic aminocyclitols antibiotic onto soap-free
      poly(MMA-EA-AA) latex particles.
AB  - Monodispersed soap-free poly(MMA-EA-AA) latex particles with surface carboxyl
      groups were synthesized by emulsion polymerization of methyl methacrylate (MMA),
      ethyl acrylate (EA) and acrylic acid (AA) in aqueous medium, and streptomycin
      sulfate (SMS) was immobilized onto these particles using three different methods.
      A model experiment was designed to test the feasibility of the reaction between
      the carboxyl groups of polymer and the amino groups of the medicine. The covalent
      coupling between the latex particles and the medicine was confirmed by XPS.
      Results showed that the medicine molecules were located on the particle surface
      after immobilization, and the coupling efficiency of SMS in pre-adsorption method
      was higher than that in direct method. The highest coupling efficiency of this
      medicine was achieved using the spacer-arm method. It was demonstrated that the
      immobilized medicine had similar antimicrobial activity as the free form using
      Escherichia coli as an evaluating organism.

PMID- 16411602
TI  - Electrospun PLGA nanofiber scaffolds for articular cartilage reconstruction:
      mechanical stability, degradation and cellular responses under mechanical
      stimulation in vitro.
AB  - We investigated the potential of a nanofiber-based poly(DL-lactide-co-glycolide)
      (PLGA) scaffold to be used for cartilage reconstruction. The mechanical
      properties of the nanofiber scaffold, degradation of the scaffold and cellular
      responses to the scaffold under mechanical stimulation were studied. Three
      different types of scaffold (lactic acid/glycolic acid content ratio = 75 : 25,
      50 : 50, or a blend of 75 : 25 and 50 : 50) were tested. The tensile modulus,
      ultimate tensile stress and corresponding strain of the scaffolds were similar to
      those of skin and were slightly lower than those of human cartilage. This
      suggested that the nanofiber scaffold was sufficiently mechanically stable to
      withstand implantation and to support regenerated cartilage. The 50 : 50 PLGA
      scaffold was degraded faster than 75 : 25 PLGA, probably due to the higher
      hydrophilic glycolic acid content in the former. The nanofiber scaffold was
      degraded faster than a block-type scaffold that had a similar molecular weight.
      Therefore, degradation of the scaffold depended on the lactic acid/glycolic acid
      content ratio and might be controlled by mixing ratio of blend PLGA. Cellular
      responses were evaluated by examining toxicity, cell proliferation and
      extracellular matrix (ECM) formation using freshly isolated chondrocytes from
      porcine articular cartilage. The scaffolds were non-toxic, and cell proliferation
      and ECM formation in nanofiber scaffolds were superior to those in membrane-type
      scaffolds. Intermittent hydrostatic pressure applied to cell-seeded nanofiber
      scaffolds increased chondrocyte proliferation and ECM formation. In conclusion,
      our nanofiber-based PLGA scaffold has the potential to be used for cartilage
      reconstruction.

PMID- 16411603
TI  - Multiphase blends from poly(L-lactide) and poly(methyl mathacrylate).
AB  - Melt processing of poly(L-lactide) (PLLA) and poly(methyl methacrylate) (PMMA)
      was conducted over a targeted range of compositions with PLLAs of 118 and 316 kDa
      in molecular mass to identify morphologies and the phase relationships in these
      blends. These blends are of interest for use in biomaterials and the morphologies
      are critical for tissue-engineering studies where biodegradability, pore
      connectivity and surface texture control tissue viability and adhesion. Simple
      extrusion of the two polymers produced multiphase blends with an average domain
      size near 25 microm. Scanning electron microscopy and dynamic mechanical analysis
      demonstrated that these blends are immiscible, at least in a metastable sense,
      and regions of co-continuous structures were identified. Such co-continuous,
      which occurred generally in accordance with rheology prediction models, exhibit a
      fine interconnected structure that appears effective for fabricating certain
      biomaterials. A broad and unexpected transition appears in these blends, as
      measured by modulated differential scanning calorimetry between 70 and 100
      degrees C, which may be the glass transition temperature of an alloy phase. The
      magnitude of this transition is greatest in the fine-structured co-continuous
      composition region of blends, suggesting the presence of a complex or other
      derivative of the two primary phases.

PMID- 16411604
TI  - Affinity evaluation of gelatin for hepatocyte growth factor of different types to
      design the release carrier.
AB  - The objective of this study was to investigate the physicochemical interaction of
      hepatocyte growth factor (HGF) and its variant with 5 amino-acid residues deleted
      (dHGF) with an acidic gelatin for the design of factors release from the gelatin
      hydrogel. When the interaction of HGF or dHGF with gelatin-immobilized agarose
      beads was evaluated by Scatchard binding assay, the dissociation constant of dHGF
      was higher than that of HGF, although the two proteins had a similar binding
      ratio. dHGF was released more rapidly from the hydrogel of acidic gelatin than
      HGF. In vivo release study with 125I-labeled HGF or dHGF in mice subcutis showed
      that HGF was released from the gelatin hydrogel as a result of hydrogel
      degradation. In contrast, dHGF was rapidly released by a simple diffusion from
      the gelatin hydrogel. From electrophoresis experiments, mixing with the acidic
      gelatin enabled HGF to complex and suppressing the trypsin-digested molecular
      weight loss, in marked contrast to that of dHGF. In addition, the percentage of
      HGF recognized by the antibody was reduced by the gelatin complexation, but that
      of dHGF was not. We conclude that unlike dHGF, HGF has a strong affinity for the
      acidic gelatin, resulting in the controlled release of HGF accompanied with
      hydrogel degradation of the release carrier.

PMID- 16411605
TI  - Evaluation of functions and tissue compatibility of poly (D,L-lactic-co-glycolic
      acid) seeded with human dermal fibroblasts.
AB  - In tissue engineering and wound-healing applications, dermal substitutes are used
      to provide fibroblasts with the mechanical support for their growth and then to
      facilitate the skin formation. In this study, three-dimensional porous
      poly(lactic-co-glycolic acid) (PLGA) 65/35 scaffolds were prepared and then the
      composites of the scaffolds and human fetal dermal fibroblasts were fabricated as
      a tissue-engineered dermal substitute. The function and tissue compatibility of
      the artificial dermal substitute were evaluated at the levels of gene expression
      (by RT-PCR) and protein expression (total collagen quantities), as well as by
      histological and immunohistochemical analysis. The PCR products indicated that
      the mRNA of type-I collagen, mainly secreted by the fibroblasts onto the PLGA
      scaffolds, was clearly expressed after 4 weeks. The amount of total collagen
      synthesized from the cells was shown to increase gradually during the initial
      culture period and slightly decreased afterwards. After 8 weeks of culture, the
      fibroblasts were well attached and migrated entirely throughout the pores of the
      PLGA scaffold with normal function. Furthermore, the positively stained type-I
      collagen was intensively detected throughout the pores. These results suggest
      that the function and tissue compatibility may be important criteria in
      evaluating an artificial tissue-engineered skin.

PMID- 16411607
TI  - Subdermal implants of poly(L-lactic acid) with plasticizer: an ultrastructural
      study in rats.
AB  - Poly(L-lactic acid) (PLLA) membranes containing 7% triethylcitrate plasticizer
      were implanted in the subcutaneous tissue of rats, and the cellular reaction was
      evaluated over a period of 2-180 days. The samples were processed for
      conventional transmission electron microscopy. Polymorphonuclear-type cells and a
      fibrin network were seen within membrane pores 2 days after implantation. In
      subsequent samples, there was cellular infiltration, which consisted mainly of
      fibroblasts, macrophages and multinuclear giant cells embedded in an abundant
      extracellular matrix containing a network of collagen fibers and blood vessels.
      At 90 and 180 days after implantation, a high density of voluminous phagocytic
      cells with a large number of endocytic polymer fragments within their cytoplasm
      was seen. These results show that PLLA membranes can support connective tissue
      proliferation and remodeling, which are important properties for successful bio
      protheses.

PMID- 16411606
TI  - Interaction of hepatocyte growth factor with gelatin as the carrier material.
AB  - The objective of this study was to physicochemically investigate the interaction
      between hepatocyte growth factor (HGF) and acidic gelatin compared with that
      between HGF and basic gelatin or heparin. Gelatin- or heparin-immobilized agarose
      beads were prepared and HGF interaction with them was evaluated by Scatchard
      binding assay. The dissociation constant of HGF with the acidic gelatin was about
      2-3 orders of magnitude higher than that of heparin. The cell proliferation assay
      revealed that the proliferation promotion activity of HGF complexed with the
      acidic gelatin was detected, although it was lower than that of original HGF. The
      ability of HGF to enhance the cell proliferation was reduced by the trypsin
      treatment, although the extent of the reduction was significantly suppressed by
      HGF complexation with acidic gelatin. Electrophoresis experimentally confirmed
      enhanced resistance to the molecular mass loss of HGF by gelatin complexation.
      Moreover, the recognized level of an antibody to HGF was reduced by the
      complexation with the acidic gelatin, indicating that the acidic gelatin is
      present around HGF molecules. It is possible that the HGF molecule is covered
      with the acidic gelatin, resulting in protection from enzymatic digestion.

PMID- 16411608
TI  - PEG-cross-linked heparin is an affinity hydrogel for sustained release of
      vascular endothelial growth factor.
AB  - An affinity-based controlled release system for growth factors having heparin
      binding domains was prepared using a cross-linked heparin gel. The heparin gel
      was made by reacting hydrazide-functionalized heparin (Hep-ADH) with the N
      hydroxysuccinimidyl ester of poly(ethylene glycol)-bis-butanoic acid (SBA-PEG
      SBA). The degree of cross-linking could be controlled by defining the
      stoichiometry of hydrazide modification and the PEG cross-linker addition. The
      release of vascular endothelial growth factor (VEGF) was characterized as a
      heparin-binding growth factor. VEGF was directly injected into the heparin gel
      and the loaded VEGF displayed a slow, controlled release over 3 weeks with little
      initial burst phase. The biological activity of the released VEGF was measured
      with a proliferation assay utilizing human umbilical vein endothelial cells. The
      released VEGF maintained its biological activity at all time points investigated.
      The heparin gel with loaded VEGF was implanted sub-cutaneously in the dorsal
      region of mice. A significantly increased density of the endothelial cell marker
      platelet endothelial adhesion molecule (PECAM-1) was observed in histological
      specimens of the tissues surrounding the implanted gel.

PMID- 16411609
TI  - Polyaniline, an electroactive polymer, supports adhesion and proliferation of
      cardiac myoblasts.
AB  - Conductive polymers, such as polypyrrole, have recently been studied as potential
      surfaces/matrices for cell- and tissue-culture applications. We have investigated
      the adhesion and proliferation properties of H9c2 cardiac myoblasts on a
      conductive polyaniline substrate. Both the non-conductive emeraldine base (PANi)
      and its conductive salt (E-PANi) forms of polyaniline were found to be
      biocompatible, viz., allowing for cell attachment and proliferation and, in the
      case of E-PANi, maintaining electrical conductivity. By comparison to tissue
      culture-treated polystyrene (TCP), the initial adhesion of H9c2 cells to both
      PANi and E-PANi was slightly reduced by 7% (P < 0.05, n = 18). By contrast, the
      overall rate of cell proliferation on the conductive surfaces, although initially
      decreased, was similar to control TCP surfaces. After 6 days in culture on the
      different surfaces, the cells formed confluent monolayers which were
      morphologically indistinguishable. Furthermore, we observed that E-PANi, when
      maintained in an aqueous physiologic environment, retained a significant level of
      electrical conductivity for at least 100 h, even though this conductivity
      gradually decreased by about 3 orders of magnitude over time. These results
      demonstrate the potential for using polyaniline as an electroactive polymer in
      the culture of excitable cells and open the possibility of using this material as
      an electroactive scaffold for cardiac and/or neuronal tissue engineering
      applications that require biocompatibility of conductive polymers.

PMID- 16411610
TI  - Methacryloylamidoglutamic acid having porous magnetic beads as a stationary phase
      in metal chelate affinity chromatography.
AB  - We have prepared a novel magnetic metal-chelate adsorbent utilizing
      methacryloylamidoglutamic acid (MAGA) as a metal-chelating ligand. MAGA was
      synthesized by using methacryloyl chloride and L-glutamic acid dihydrochloride.
      Magnetic beads with an average diameter of 50-100 microm were produced by
      suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) and MAGA in the
      presence of Fe3O4 particles carried out in an aqueous dispersion medium. Magnetic
      beads were charged with the Cu2+ ions directly via MAGA for the adsorption of
      cytochrome c (cyt c) from aqueous solutions. The maximum cyt c adsorption
      capacity of the Cu2+-chelated beads (0.86 mmol/g Cu2+ loading) was found to be 37
      mg/g at pH 8.0 in phosphate buffer. Cyt c adsorption on the poly(HEMA-MAGA) beads
      was 15.4 mg/g. Cu2+ charging increased the cyt c adsorption significantly (37
      mg/g). Cyt c adsorption decreased with increasing temperature. Cyt c molecules
      could be adsorbed and desorbed five times with these adsorbents without
      noticeable loss in their cyt c adsorption capacity. The resulting magnetic
      chelator beads posses excellent long term storage stability.

PMID- 16411611
TI  - Atomic force microscopy visualization of poly(urethane urea) microphase
      rearrangements under aqueous environment.
AB  - Polyurethane biomaterials are a critically important class of polymers used in a
      variety of medical devices. It has been suggested that the good blood
      compatibility of polyurethanes arises from nanoscale chemical heterogeneities at
      the surface as a consequence of the microphase separated morphology. In this
      study, we used tapping mode atomic force microscopy with phase imaging under
      aqueous conditions to visualize the distribution of the surface microphases for a
      series of poly(urethane urea) block co-polymers with varying hard segment
      content. The surfaces were prehydrated for 24 h under a flow of 1 mM phosphate
      buffer. Topographic images showed the formation of nanometer-sized raised
      features on the surface, having lateral dimensions of 50-70 nm and heights of 10
      15 nm. Phase images, reflecting the local distribution of the mechanical
      properties under aqueous conditions, were quite different from those obtained in
      ambient conditions, consistent with water-induced structural reorientation.
      Images suggest that there is little soft phase material at the polymer surface in
      the presence of water, while images acquired after dehydration of the samples
      show that the surface layer remains rich in hard domains, indicating that the
      films do not return to their original states over the time period studied.

PMID- 16411612
TI  - Staphylococcus epidermidis adhesion on modified urea/urethane elastomers.
AB  - Block urea/urethane co-polymer films present elastomeric properties with the
      possible tuning of their surface properties within a wide range and are therefore
      considered relevant surfaces for possible medical applications. In particular,
      thin free standing films of urea/urethane elastomers with two soft segments,
      polypropylene oxide and more hydrophobic polybutadiene, develop multistable
      states with surface topography features with remarkable regularity. Moreover,
      complex surface structures may be obtained by UV radiation treatment followed by
      suitable mechanical action and also by extraction of the elastomer with a
      suitable solvent. In the present work, different modified elastomer samples were
      assayed for Staphylococcus epidermidis adhesion during 2 h and the extent of
      bacterial adhesion was evaluated by automatic cell enumeration. Bacterial
      adhesion assays demonstrate that the typical trend relating the increase in the
      number of adhered bacteria with the increase of the surface roughness does not
      hold for all materials. Results may be interpreted taking into account both the
      surface topography and the different types of micro-phase segregation of
      hydrophobic and hydrophilic parts of the elastomer.

PMID- 16411613
TI  - Which pulmonary volume should be used in physiotherapy to obtain higher maximal
      inspiratory pressure in COPD patients?
AB  - BACKGROUND AND PURPOSE: Patients with chronic obstructive pulmonary disease
      (COPD) present pulmonary hyperinflation as the main cause of mechanical
      disadvantages in respiratory muscles. Measurement of the force generated by those
      muscles is converted into pressure changes. The aim of the present study was to
      evaluate the maximal inspiratory pressure (MIP) from the residual volume (RV) and
      from the functional residual capacity (FRC), in patients with COPD, and to
      determine which pulmonary volume should be used in physiotherapy so as to obtain
      higher MIP results. METHOD: An investigation of 18 male patients with stable
      COPD. Patients were examined using a manual vacuometer to measure the MIP of 20
      daily manoeuvres. Ten measurements were taken from the RV and 10 from the FRC,
      taken alternately with an interval of 1 minute between each measurement, for five
      consecutive days. RESULTS: Increases in MIP were obtained from the RV
      measurements (mean +/- SE) from 59.7 (+/- 5.2) to 66.6 (+/- 5.3) cm H2O (F(4,64)
      = 3.34; p < 0.015) and from the FRC measurements, from 55.4 (+/- 4.9) to 64.4 (+/
      4,8) cm H2O (F(4,64) = 6.72; p < 0.001). Post hoc analysis showed an increase,
      over consecutive days, in both RV and FRC. For FRC, an increase was revealed on
      the second and third days, a fall was found on the fourth day and a new increase
      was found on the last day. MIP reached different levels, between RV and FRC, on
      the first (t = 2.888; p = 0.010) and fourth (t = 2.165; p = 0.045) days.
      CONCLUSION: In the present study, MIP reached higher levels at FRC during the
      five days of evaluation, and a learning effect occurred in the patients. Motor
      units from the respiratory muscles may have been recruited in order to perform
      the manoeuvres during the days of evaluation. The study suggests that there is
      good evidence for the use of the FRC as a parameter to find the major MIP value.

PMID- 16411614
TI  - Procedural considerations for photographic-based joint angle measurements.
AB  - BACKGROUND AND PURPOSE: Measuring static joint angles is important to clinicians
      involved in assessing, diagnosing and treating musculoskeletal disorders. New
      measurement techniques such as the Uillinn Method (UM) employ the relatively new
      technology of digital photography and software to form a virtual goniometer. It
      is of central importance that the errors associated such new measurement
      techniques are known. Precision in joint angle measurement is a challenge and
      errors can arise from three separate categories: equipment error, examiner error
      or biological error. The aim of the present study was to discover the amount of
      equipment error associated with the UM and to present guidelines for the optimal
      use of a photographic based measurement technique. METHOD: This was a non
      clinical agreement study design that attempted to describe the best possible
      agreement between a mathematical control dataset and the angles calculated from
      the virtual goniometer, which in this case was the UM. When this was established,
      the effect of rotation and placing the angle at the periphery of the camera's
      field of view were tested. RESULTS: The repeatability coefficient (RC) between
      the UM and the control data under optimal conditions was 0.81 degrees; the
      typical error (TE) was 0.29 degrees (n = 120). When the angle appeared at the
      edge of the photograph the RC increased to 2 degrees and the TE to 0.73 degrees
      (n = 48). When 5 degrees rotation was introduced between the camera and the angle
      no increase in error was detected. However, increasing amounts of rotation above
      5 degrees was proportional to increases in the RC (RC at 10 degrees = 2.3 degrees
      20 degrees = 3.86 degrees; 30 degrees = 14.8 degrees; 40 degrees = 27.27 degrees)
      and the TE (TE at 10 degrees = 0.83 degrees; 20 degrees = 2.7 degrees; 30 degrees
      = 5.3 degrees; 40 degrees = 9.8 degrees) scores. CONCLUSION: Photographic-based
      joint angle measurement techniques are subject to error if careful procedures are
      not observed. Best procedures include photography from a perpendicular viewpoint
      and centring the lens on the target angle.

PMID- 16411615
TI  - Physiotherapy management of low back pain in Thailand: a study of practice.
AB  - BACKGROUND AND PURPOSE: Low back pain (LBP) is one of the most common
      musculoskeletal disorders in both developed and developing countries. Whilst
      there have been a number of studies investigating the current physiotherapy
      management of LBP in the former, little is known about such management in
      developing countries. The objectives of the present study were to investigate the
      physiotherapy management of LBP in Thailand and to compare the results with those
      of developed countries where applicable. METHOD: A cross-sectional survey was
      undertaken to collect information on physiotherapists, LBP patients and treatment
      interventions used, using a Thai version of an available (English) questionnaire.
      Subsequent to a pilot study with 32 Thai therapists, minor revisions were made
      and the final questionnaires were mailed to all 776 physiotherapists currently
      working throughout Thailand. RESULTS: Responses were received from 559 therapists
      (a 77.2% response rate), and 502 of these were currently involved in LBP
      management. Results indicated that LBP patients made up, on average, 37.5% of
      their patient caseloads. Electrophysical modalities, especially hot packs (64%),
      ultrasound (61%) and mechanical traction (61%), were reported to be the most
      commonly used treatments, particularly by hospital-based therapists, whereas
      those working in university-based hospitals and private clinics were more likely
      to use manual therapy. CONCLUSIONS: This study provides descriptive data from the
      therapists' perspective about LBP management and shows that the treatments most
      commonly used are different from those treatments commonly used in developed
      countries. The potential reasons for this are explored in this paper and
      recommendations are made for further research.

PMID- 16411616
TI  - Effect of expiratory flow increase technique on pulmonary function of infants on
      mechanical ventilation.
AB  - BACKGROUND AND PURPOSE: Although chest physiotherapy techniques are commonly used
      in the treatment of respiratory diseases, there are, however, few studies in the
      literature on the effectiveness of these techniques in paediatric patients. The
      purpose of the present study was to evaluate the effect of the expiratory flow
      increase technique (EFIT) on the pulmonary function of infants on invasive
      mechanical pulmonary ventilation. METHOD: A prospective, non-randomized study
      design was used, with consecutive enrolment conducted in the paediatric intensive
      care unit (PICU) of a university hospital. All infants with acute obstructive
      respiratory failure who were on invasive mechanical pulmonary ventilation between
      April 2001 and April 2003 were included in this study. Respiratory rate, PaO2,
      PaCO2, SatO2, PaO2/FiO2, P(A-a)O2/PaO2, PaO2/PAO2, VD/VT, dynamic compliance,
      inspiratory and expiratory resistance values were compared before and after
      application of the EFIT. RESULTS: Blood gas and pulmonary function measurements
      were recorded before and after EFIT. Repeated-measures analysis of variance
      (ANOVA) was used. The results were considered statistically significant when p
      values were < 0.05. Twenty-two infants were enrolled. There was a significant
      increase in respiratory rate, SatO2 and PaO2/PAO2 and a significant decrease in
      P(A-a)O2/PaO2 after application of the EFIT. CONCLUSION: There was a short-term
      improvement in the oxygenation of infants who were submitted to the EFIT.
      Additional studies are necessary to establish the efficacy and effectiveness of
      this technique.

PMID- 16411617
TI  - Case report: inspiratory muscle training in chronic critically ill patients--a
      report of two cases.
AB  - BACKGROUND AND PURPOSE: Inspiratory muscle weakness and fatigue has been
      documented following prolonged mechanical ventilation despite successful weaning
      from mechanical ventilation. This report describes the application of inspiratory
      muscle training in two patients following successful discharge from an intensive
      care unit (ICU) after prolonged mechanical ventilation. METHODS: Both patients
      undertook inspiratory muscle training in conjunction with standard physiotherapy
      rehabilitation. RESULTS: Improvements in inspiratory muscle strength and
      endurance, exercise tolerance and functional performance following twice-daily
      inspiratory muscle training were recorded. In both cases, an improvement in
      maximal inspiratory pressure (MIP) and maximal tolerated inspiratory load
      (MIP(load)) was found following training. CONCLUSION: These positive results
      indicate further research is needed to investigate the effect of inspiratory
      muscle training on respiratory function, exercise tolerance and functional
      performance, for the possible inclusion of inspiratory muscle training into the
      physiotherapy management of patients following prolonged mechanical ventilation.

PMID- 16411618
TI  - Case report: community rehabilitation for a patient with incomplete spinal cord
      lesion.
AB  - This is a case report of Mr S, a 43-year-old man with a spinal cord lesion caused
      by tuberculosis resulting in incomplete paraplegia. He was discharged from
      hospital with significant residual disability. He received a major part of his
      rehabilitation in the community from an interdisciplinary neuro rehabilitation
      team with good results. Because Mr S was overweight, over 20 stones, the
      therapists had to use considerable creativity and imagination to facilitate his
      rehabilitation. Mr S's high level of motivation and courage was essential to the
      success achieved. The purpose of the case report is to demonstrate that a
      positive outcome can be achieved despite the many difficulties faced in the
      rehabilitation of an overweight patient with an incomplete spinal cord lesion in
      a community setting.

PMID- 16411619
TI  - A clinical dilemma: to treat or not to treat in the presence of a pulmonary
      foreign body?

PMID- 16411620
TI  - The UK population at the start of the 21st century.

PMID- 16411621
TI  - Population estimates; backseries methodology for 1992-2000.
AB  - In each decade, population estimates are rebased using data from the most recent
      census. However, this would lead to a step change in the population estimates
      series. To avoid this discontinuity the backseries for 1992 to 2000, was revised
      to bring it into line with the 2001 Census. This article discusses the
      methodology used to produce the final revised backseries for 1992 to 2000
      published by ONS in October 2004. The final estimates were produced after a long
      period of research into the best methodology to use. Traditionally, the
      backseries have been revised using an interim simple period method, followed by a
      final simple cohort method. The approach taken following the 2001 Census was much
      more comprehensive. This article outlines this approach, summarises the range of
      methods available and describes in detail the final method selected.

PMID- 16411622
TI  - Making an estimate of the number of people and households for Output Areas in the
      2001 Census.
AB  - This article describes an investigation into the best way to estimate robust
      totals for people and households at Output Area level. We show that computing the
      average of people and household counts across the set of tables in which the same
      count appears is a good strategy. When we compare the mean or median person and
      household counts with those produced by summing from the postcode directory, the
      two sets of numbers are usually very close. Using averages in this way for other
      population bases in the sets of tables is therefore recommended. This technique
      can also be applied to larger areas.

PMID- 16411623
TI  - Living arrangements in contemporary Britain: having a partner who usually lives
      elsewhere and living apart together (LAT).
AB  - This article explores the subject of 'living apart together' (LAT). LAT is a
      relationship in which the two partners regard themselves as a couple but they are
      not co-residentially cohabiting. The phenomenon of 'living apart together' is
      difficult to measure but has become increasingly recognised in international
      sociological and demographic literature. However, in Great Britain there has so
      far been little research of this subject and no attempt, until now, to estimate
      its extent.

PMID- 16411625
TI  - Evaluation of a fall detector based on accelerometers: a pilot study.
AB  - As falls and fall-related injuries remain a major challenge in the public health
      domain, reliable and immediate detection of falls is important so that adequate
      medical support can be delivered. Available home alarm systems are placed on the
      hip, but have several shortcomings. A fall detector based on accelerometers and
      placed at head level was developed, as well as an algorithm able to distinguish
      between activities of daily living and simulated falls. Accelerometers were
      integrated into a hearing-aid housing, which was fixed behind the ear. The
      sensitivity of the fall detection was assessed by investigation into the
      acceleration patterns of the head of a young volunteer during intentional falls.
      The specificity was assessed by investigation into activities of daily living of
      the same volunteer. In addition, a healthy elderly woman (83 years) wore the
      sensor during the day. Three trigger thresholds were identified so that a fall
      could be recognised: the sum-vector of acceleration in the xy-plane higher than 2
      g; the sum-vector of velocity of all spatial components right before the impact
      higher than 0.7 m s(-1); and the sum-vector of acceleration of all spatial
      components higher than 6 g. The algorithm was able to discriminate activities of
      daily living from intentional falls. Thus high sensitivity and specificity of the
      algorithm could be demonstrated that was better than in other fall detectors worn
      at the hip or wrist at the same stage of development.

PMID- 16411626
TI  - Instrumented staircase for kinetic analyses of upper- and lower-limb function
      during stair gait.
AB  - The paper describes the design, technical characteristics and first results of an
      adjustable staircase with commercial force plates embedded in the steps and
      custom force transducers as part of the handrail supports. For the railing
      assembly, the greatest errors (< 10% of maximum signal) and cross-talk range
      (0.58-6.74%) were in the medial-lateral direction and were corrected using a
      calibration matrix. Power spectral density analyses showed free vibration
      frequency responses for both the railing (15 Hz) and steps (38.6 Hz) that were
      relatively distinct from lower applied forces recorded during stair ascent. The
      creation of standardised filtering protocols was therefore possible to provide
      step reaction force signals identical to the literature and examples of upper
      limb reaction forces that have not been shown before. Such a staircase will allow
      a more complete study of full body contributions to stair walking across various
      subject populations.

PMID- 16411627
TI  - Estimation of atrial fibrillatory wave from single-lead atrial fibrillation
      electrocardiograms using principal component analysis concepts.
AB  - A new method for the assessment of the atrial fibrillatory wave (AFW) from the
      ECG is presented. This methodology is suitable for signals registered from Holter
      systems, where the reduced number of leads is insufficient to exploit the spatial
      information of the ECG. The temporal dependence of the bio-electrical activity
      were exploited using principal component analysis. The main features of
      ventricular and atrial activity were extracted, and several basis signals for
      each subspace were determined. Hence, the estimated (AFW) are reconstructed
      exclusively from the basis signals that formed the atrial subspace. Its main
      advantage with respect to adaptive template subtraction techniques was its
      robustness to variations in the QRST morphology, which thus minimised QRST
      residua. The proposed approach was first validated using a database of simulated
      recordings with known atrial activity content. The estimated AFW was compared
      with the original AFW, obtaining correlation indices of 0.774 +/- 0.106. The
      suitability of this methodology for real recordings was also proven, though its
      application to a set of paroxysmal AF ECGs. In all cases, it was possible to
      detect the main frequency peak, which was between 4.6 Hz and 6.9 Hz for the
      patients under study.

PMID- 16411624
TI  - Evaluation of antidecubitus mattresses.
AB  - Pressure sores are a current problem in hospitals and care of the elderly,
      leading to protracted hospital stays and a high care burden. The trauma for the
      patients is severe, and the cost of pressure sore prevention and treatment, is
      considerable. Antidecubitus mattresses are used for prevention and in treatment,
      but they also contribute to the cost of treating pressure sores. The problem
      highlighted in the review is that the mattresses' effectiveness in preventing and
      treating pressure sores has not been sufficiently evaluated. When antidecubitus
      mattresses are evaluated, it is often only with regard to aspects of the
      interface pressure and the mattresses' ability to redistribute the pressure. The
      review points out the important observation that, to be able to evaluate the
      efficacy of the antidecubitus mattress, the mattress's effect on tissue viability
      needs to be studied. The parameters that ought to be considered when evaluating a
      support surface are: interface pressure, pressure and blood flow distribution,
      temperature and humidity in the skin-support surface interface. The authors
      propose that the effect on tissue viability of external loading can be assessed
      by simultaneous measurement of the interface pressure and tissue perfusion.

PMID- 16411628
TI  - Atrial cell action potential parameter fitting using genetic algorithms.
AB  - Understanding of the considerable variation in action potential (AP) shape
      throughout the heart is necessary to explain normal and pathological cardiac
      function. Existing mathematical models reproduce typical APs, but not all
      measured APs, as fitting the sets of non-linear equations is a tedious process.
      The study describes the integration of a pre-existing mathematical model of an
      atrial cell AP with a genetic algorithm to provide an automated tool to generate
      APs for arbitrary cells by fitting ionic channel conductances. Using the Nygren
      model as the base, the technique was first verified by starting with random
      values and fitting the Nygren model to itself with an error of only 0.03%. The
      Courtemanche model, which has a different morphology from that of the Nygren
      model, was successfully fitted. The AP duration restitution curve generated by
      the fit matched that of the target model very well. Finally, experimentally
      recorded APs were reproduced. To match AP duration restitution behaviour
      properly, it was necessary simultaneously to fit over several stimulation
      frequencies. Also, fitting of the upstroke was better if the stimulating current
      pulse replicated that found in situ as opposed to a rectangular pulse. In
      conclusion, the modelled parameters were successfully able to reproduce any given
      atrial AP. This tool can be useful for determining parameters in new AP models,
      reproducing specific APs, as well as determining the locus of drug action by
      examining changes in conductance values.

PMID- 16411629
TI  - Suppression of the cardiac electric field artifact from the heart action evoked
      potential.
AB  - The study of heart action-related brain potentials is strongly disrupted by the
      presence of an inherent cardiac electric artifact. The hypothesis is presented
      that most of the electric current coupled to the cardiac field surrounds the
      skull and flows through the scalp tissue without crossing the cranial cavity.
      This pseudo two-dimensional conduction model contrasts with the volumetric
      conduction of the brain electrical activity, and this property is exploited to
      cancel the cardiac electric artifact. QRS loop vector-cardiographic projections
      on saggital planes were recorded in 11 healthy subjects in the head and neck
      areas. Comparative analysis of the projection eccentricities, estimated by the
      correlation coefficients of the paired data on each area, supported the
      hypothesis and allowed the handling of the cardiac electric field at the scalp as
      if enclosed in a two-dimensional wrapped space. This approach permitted the
      combination of different heart action-related brain potentials recorded at
      different electrode positions to cancel the cardiac electric artifact. The
      cancellation method, applied to the subjects' EEG data, yielded a slow cortical
      potential with a negligible cardiac electric residue and an amplitude of about
      1.5-2 microV, with a maximum around 150 ms and a minimum at 400 ms post-R wave.

PMID- 16411630
TI  - Myocardial perfusion monitoring during coronary artery bypass using an
      electrocardiogram-triggered laser Doppler technique.
AB  - Electrocardiogram (ECG)-triggered laser Doppler perfusion monitoring (LDPM) was
      used to assess myocardial perfusion, with minimum myocardial tissue motion
      influence, during coronary artery bypass grafting (CABG). Thirteen subjects were
      investigated at six phases: pre- and post-CABG; post aorta cross-clamping; pre
      and post left internal mammary artery (LIMA) graft declamping; and post aorta
      declamping. The perfusion signal was calculated in late systole and late
      diastole, with expected minimum tissue motion, and compared with arrested heart
      measurements. Patient conditions or artifacts caused by surgical activity made it
      impossible to perform and analyse data in all six phases for some patients. No
      significant (n = 5) difference between perfusion signals pre- and post-CABG was
      found. Diastolic perfusion signal levels were significantly (p < 0.02) lower
      compared with systolic levels. After aorta cross-clamping, the signal level was
      almost zero. A distinct perfusion signal increase after LIMA and aorta
      declamping, compared with pre-LIMA declamping, was found in ten cases out of 13.
      A significantly (p < 0.04) lower perfusion signal in the arrested heart compared
      with in the beating heart was registered. Influence from mechanical ventilation
      was observed in 14 measurements out of 17. In conclusion, ECG-triggered LDPM can
      be used to assess myocardial perfusion during CABG. Perfusion signals were lower
      in the arrested heart compared with in the beating heart and in late diastole
      compared with late systole. No significant difference between pre- and post-CABG
      was found.

PMID- 16411631
TI  - Robust and self-tuning blood flow control during extracorporeal circulation in
      the presence of system parameter uncertainties.
AB  - Three different discrete controllers were designed and tuned to be used in
      conjunction with a rotary blood pump during cardiopulmonary heart-lung support.
      The controllers were designed to operate in both steady and pulsatile modes. The
      system and methods were tested in a circulatory haemodynamic simulator. To
      guarantee stable control of the non-linear circulatory system in the presence of
      patient parameter uncertainties, a proportional plus integral (PI) and an H
      infinity controller were robustly tuned, using a non-linear time-varying model.
      (H infinity refers to the Hardy space, the set of bounded functions, analytic in
      the right half plane. The H infinity controller is the solution to the H infinity
      norm optimisation problem.) A self-tuning general predictive controller (GPC),
      together with an adaptive Kalman filter (KF) estimator, was compared with the two
      robustly tuned controllers. The closed-loop blood flow control circuit was set up
      in simulation routines first. The blood flow controllers were validated in a
      circulatory hydrodynamic simulator (MOCK) combined with a rotary blood pump.
      Parameters of the system simulator were changed continuously, and the controllers
      were tested over a wide range of different operating points. Disturbances in the
      form of discontinuous additive parameter uncertainties were applied. The closed
      loop systems remained robustly stable. The robustly tuned H infinity controller
      showed the best control performance, in contrast to the GPC controller, which was
      near instability in regions of strongly varying non-linear system gain. Compared
      with the H infinity controller, the PI controller showed slightly worse
      behaviour, but the closed-loop response was acceptable, even in regions of
      strongly varying non-linear system gain and during pulsatile perfusion. The
      rotary blood pump could provide stationary and pulsatile perfusion under control
      conditions. Controlled variables were hereby mean blood flow, pulsatility index
      and heart rate. All three controllers were developed for an arterial mean flow of
      0-6 l min(-1) and a heart rate of up to 70 beats per minute. Pulsatile closed
      loop perfusion could provide up to 30 mmHg pressure variation in the simulated
      ascending aorta at a mean flow of 3 l min(-1).

PMID- 16411632
TI  - Amplitude and phase relationship between alpha and beta oscillations in the human
      electroencephalogram.
AB  - The relationship between the electro-encephalographic (EEG) alpha and beta
      oscillations in the resting condition was investigated in the study. EEGs were
      recorded in 33 subjects, and alpha (7.5-12.5 Hz) and beta (15-25 Hz) oscillations
      were extracted with the use of a modified wavelet transform. Power, peak
      frequency and phase synchronisation were evaluated for both types of oscillation.
      The average beta-alpha peak frequency ratio was about 1.9-2.0 for all electrode
      derivations. The peak frequency of beta activity was within 70-90 % of the 95 %
      confidence interval of twice the alpha frequency. A significant (p < 0.05) linear
      regression was found between beta and alpha power in all derivations in 32
      subjects, with the slope of the regression line being approximately 0.3. There
      was no significant difference in the slope of the line in different electrode
      locations, although the power correlation was strongest in the occipital
      locations where alpha and beta oscillations had the largest power. A significant
      1:2 phase synchronisation was present between the alpha and beta oscillations,
      with a phase lag of about pi/2 in all electrode derivations. The strong frequency
      relationship between the resting beta and alpha oscillations suggests that they
      are generated by a common mechanism. Power and phase relationships were weaker,
      suggesting that these properties can be modulated by additional mechanisms as
      well as be influenced by noise. A careful distinction between alpha-dependent and
      alpha-independent beta activity should be considered when making statements about
      the possible significance of genuine beta activity in different
      neurophysiological mechanisms.

PMID- 16411633
TI  - Simulation of intra-orbital optic nerve electrical stimulation.
AB  - In blind subjects who still have functional retinal ganglion cells, electrical
      stimuli applied to the optic nerve can produce localised visual sensations. This
      has been demonstrated with an intracranially implanted self-sizing spiral cuff
      electrode, but, to avoid skull opening, intra-orbital cuff implantation is now
      considered. In its orbital segment, the optic nerve is surrounded by
      subarachnoidal cerebrospinal fluid (CSF) and dura mater. Dura mater is a tough
      fibrous tissue that can impede electrical stimulation. In the study, the issue of
      whether or not to remove the dura mater at the implantation site was addressed
      using simulation on numerical models. Several volume conductor models were built
      representing, respectively: the cuff implanted directly around the nerve; the
      cuff over the nerve after connective tissue encapsulated the implant; and the
      cuff electrode placed around the dura mater. Stimulation-induced electric
      potential fields were computed for these configurations using a full 3D finite
      elements software. Responses of fibres within the nerve were computed. A large
      range of dural conductivities and several CSF thicknesses were considered. In all
      simulated conditions, the presence of dura mater around a layer of CSF increased
      excitation thresholds. Selectivity performance also decreased, but was found to
      be independent of the CSF thickness. However, simulations showed that, if the
      diameter of the cuff electrode is adapted to the target nerve, the injected
      charge associated with activation is limited within a reasonable range.
      Electrical stimulation of the optic nerve with a cuff electrode implanted around
      the dura mater should therefore be feasible.

PMID- 16411634
TI  - Noise from implantable Cooper cable.
AB  - Cooper cable is made for implanted devices, usually for connection to stimulating
      electrodes. An experiment has been performed to see whether these cables would be
      satisfactory for recording electroneurogram (ENG) signals from cuffs. Four cables
      were subjected to continuous flexion at 2 Hz while submerged in saline. The
      cables were connected to a low-noise amplifier, and the noise was measured using
      a spectrum analyser. These cables had not fractured after 184 million flexions,
      and the noise in the neural band (500-5000 Hz) had not increased owing to age.
      Noise in the ENG band increased by less than 3 dB owing to the motion. A fifth,
      worn cable did fail during the experiment, the conductors becoming exposed to the
      saline, but this was only apparent by extra noise when the cable was in motion.
      After 184 million flexions, the four cables were given a more severe test:
      instead of being connected to the amplifier reference node, two of the four cores
      of each cable were connected to 18V batteries. Two of the cables were then
      noisier, but only when in motion, presumably because of leakage between cores.
      Cooper cables are excellent for transmitting neural signals alone; transmission
      in one cable of neural signals and power supplies should be avoided if possible.

PMID- 16411635
TI  - Lidocaine transport through living rat skin using alternating current.
AB  - The purpose of the study was to determine whether lidocaine could be transported
      through living rat skin using alternating current and to determine whether
      lidocaine transport depends on voltage. The drug delivery cell was originally
      constructed for the application of an electric field. Hairless rats were
      anaesthetised using sevoflurane, and a tracheotomy was performed. The drug
      delivery cell, with lidocaine solution in the donor cell, was placed on the
      abdominal skin. Samples were collected from the subcutaneous tissue using a
      microdialysis probe inserted into the abdominal subcutaneous tissue, and the
      lidocaine concentrations in the samples were determined using high-performance
      liquid chromatography. The lidocaine concentration in the rat skin increased in
      time, and voltage-dependency was approximately linear. The lidocaine
      concentration after the application of 20 V for 21 min was about ten-fold higher
      than that observed after 21 min of passive diffusion. Lidocaine was successfully
      transported through living rat skin in a voltage- and time-dependent manner. This
      drug delivery cell may contribute to local anaesthesia and pain management of
      human skin.

PMID- 16411636
TI  - Reduction of noise from magnetoencephalography data.
AB  - A noise reduction method for magnetoencephalography (MEG) data is proposed. The
      method is a combination of Kalman filtering and factor analysis. A state-space
      model for a Kalman filter was constructed using the forward problem in MEG
      measurement. Factor analysis provide estimations of noise covariances required by
      the Kalman filter to eliminate independent additive sensor noise. The proposed
      method supports independent component analysis (ICA), which is difficult to use
      in MEG analysis owing to the sensor noise. Numerical experiments were conducted
      to investigate the performance of the proposed method. In a single dipole case
      where the maximum signal-to-noise ratio (SNR) was -10 dB, approximately
      equivalent to raw MEG data, noise-free signals were successfully estimated from
      noisy data; a 0.02 s delay of the peak latency and 15-40% of attenuation of the
      peak amplitude were observed. Moreover, in a multiple dipole case, independent
      components preprocessed with the proposed method had high correlation, 0.88 at
      the lowest, with correlation of 0.69 and 0.52 for those preprocessed with
      conventional bandpass filters. The results show that the noise reduction method
      reduces sensor noise effectively. High SNR-independent components are obtained by
      the proposed method. Real MEG data analysis was also demonstrated. The proposed
      method extracted auditory evoked responses from unaveraged single-trial data.

PMID- 16411637
TI  - Adaptive filtering of evoked potentials using higher-order adaptive signal
      enhancer with genetic-type variable step-size prefilter.
AB  - An adaptive signal enhancer based on third-order statistics with a genetic-type,
      variable step-size prefilter is introduced to recover evoked potentials (EPs).
      EPs are usually embedded in the ongoing electroencephalogram with a very low
      signal-to-noise ratio (SNR). As a higher-order statistics technique has a natural
      tolerance to Gaussian noise, it is applicable for filtering EPs. An adaptive
      signal enhancer based on third-order statistics was used as the major filter in
      this study. However, the efficiency of the adaptive signal enhancer was reduced
      when the total power of uncorrelated noises was large. To improve the performance
      for EPs under poor SNR, a low-noise signal is required. Therefore a prefilter
      with a genetic-type, variable step-size algorithm was employed to enhance the SNR
      of the signal in this study. The fundamental idea of a genetic-type, variable
      step-size algorithm is that its step-sizes are regularly readjusted to optimum.
      Therefore this algorithm can be used as a prefilter with different noise levels.
      Experimental results showed that, for filtering EPs, the proposed scheme is
      superior to the adaptive signal enhancer with a normalised least mean square
      algorithm.

PMID- 16411638
TI  - Genetic algorithm for the efficient selection of disyllabic word lists used in
      Mandarin speech discrimination tests.
AB  - Speech audiometric tests have been widely used for advanced hearing diagnoses and
      in rehabilitation. However, there are no standardised speech tests for more than
      90% of the world's population, who do not speak English. A major problem in the
      design of a speech audiometric test is that the selection of test materials is
      subject to multiple criteria, and its complexity rises dramatically as the
      structure of test items changes from phonemic or monosyllabic forms to disyllabic
      or polysyllabic forms. A genetic algorithm is presented that can automatically
      select a set of disyllabic words from a large Mandarin corpus. The selection
      accords with the following principal criteria for the items constituting a speech
      discrimination test: similarity in structure, familiarity to the subjects, and a
      phonemically balanced composition. The performance of the genetic algorithm was
      evaluated by computation of the distance between a target vector, specifying the
      desired distribution of initial and final syllables and tone patterns for daily
      disyllabic word usage, and the vector derived by the search results of the
      algorithm. The use of the genetic algorithm was illustrated by its application to
      the selection of test lists from two Mandarin corpora. The results showed that,
      for a given corpus, at least 12 disyllabic word lists with a distance of less
      than 20 could be generated within 72 h. The genetic algorithm performed an
      efficient, robust and low-complexity search of the problem space and can be
      easily modified to adapt to the material selection of other languages.

PMID- 16411640
TI  - CT-3D rotational angiography automatic registration: a sensitivity analysis.
AB  - Preprocessing, binning and dataset subsampling are investigated with regard to
      simultaneous maximisation of the speed, accuracy and robustness of CT-3D
      rotational angiography (3DRA) registration. Clinical diagnosis and treatment can
      both take advantage of this integration, because 3DRA allows the shape of vessel
      structures to be evaluated three-dimensionally with respect to standard 2D
      projective angiography. The method for optimising preprocessing, binning and
      subsampling consisted of independent variation of the corresponding parameters to
      maximise robustness and speed while maintaining subvoxel accuracy; the latter was
      computed as the sum of the mean squared errors initially present in the
      registrations with the errors relative to both binning and subsampling. The
      results suggest the choice of 256 bins, steps between 14 mm (coarse optimisation)
      and 2.5 mm (fine optimisation) and bone segmentation by threshold, for binning,
      subsampling and preprocessing, respectively. The application of this parameter
      set-up to 50 CT-3DRA registrations resulted in a saving, on average, of 40% of
      the time with respect to the method previously used, while registration error was
      maintained within 2 mm (1.97 mm, 90% confidence interval) and robustness was
      increased, so that no manual initial realignment was needed in 48 registrations.
      Validation by the registration of images acquired for a head phantom showed
      subvoxel residual errors. In conclusion, the proposed procedure can be considered
      a satisfactory strategy to optimise CT-3DRA registration.

PMID- 16411639
TI  - In vitro measurements of optical properties of porcine brain using a novel
      compact device.
AB  - Knowledge of the optical properties of tissues can be applied in numerous medical
      and scientific fields, including cancer diagnostics and therapy. There are many
      different ways of determining the optical properties of turbid media. The paper
      describes measurements of the optical properties of porcine brain tissue using
      novel instrumentation for simultaneous absorption and scattering characterisation
      of small turbid samples. Integrating sphere measurements are widely used as a
      reference method for determination of the optical properties of relatively thin
      turbid samples. However, this technique is associated with bulky equipment,
      complicated measuring techniques, interference compensation techniques and
      inconvenient sample handling. It is believed that the sphere for some
      applications can be replaced by a new, compact device, called the combined
      angular and spatially resolved head sensor, to measure the optical properties of
      thin turbid samples. The results compare very well with data obtained with an
      integrating sphere for well-defined samples. The instrument was shown to be
      accurate to within 12% for microa and 1% for micro's in measurements of
      intralipid-ink samples. The corresponding variations of data were 17% and 2%,
      respectively. The reduced scattering coefficient for porcine white matter was
      measured to be 100 cm(-1) at 633 nm, and the value for coagulated brain tissue
      was 65 cm(-1). The corresponding absorption coefficients were 2 and 3 cm(-1),
      respectively.

PMID- 16411641
TI  - Automatic analysis of immunocytochemically stained tissue samples.
AB  - An automatic colour image segmentation and cell counting software system has been
      developed for immunocytochemical analysis of stained tissue samples. The system
      was designed to count the total number of positive and negative cells in tissue
      samples treated with cytokine DNA probes from pigs naturally parasitised with
      Taenia solium metacestodes, using in situ hybridisation. A reaction index was
      calculated as the ratio of the number of cells with a positive reaction to the
      total number of cells (positives plus negatives) for each of five different
      probes. The objectives of automatic counting were to improve the reproducibility
      of the analysis and reduce the processing time of large image batches. A fast KNN
      classifier was used for colour segmentation. Watershed segmentation combined with
      edge detection was used to isolate individual cells that were then automatically
      labelled, using the results of the corresponding colour segmented image.
      Validation was performed on 122 non-training digital images with a total of 1069
      positive cells and 1459 negative cells, with the following results: a mean true
      positive rate of 90.2% for positive cells and a mean true positive rate of 85.4%
      for negative cells. The corresponding mean false positive rates were 9.6% and
      6.6%. The mean reaction index error of the automatic analysis was 5.35%. The
      processing of each digital image took 10 s on a Pentium IV PC.

PMID- 16411642
TI  - Parametric image of myocardial blood flow generated from dynamic H2(15)O PET
      using factor analysis and cluster analysis.
AB  - Algorithm-based parametric imaging of myocardial blood flow (MBF), as measured by
      H2(15)O PET, has been the goal of many research efforts. A method for generating
      parametric images of regional MBF by factor and cluster analysis on H2(15)O
      dynamic myocardial PET was validated by its comparison with gold-standard MBF
      values determined invasively using radiolabelled microspheres. Right and left
      ventricular blood pool activities and their factor images were obtained by the
      application of factor analysis to dynamic frames. By subtraction of the factor
      images multiplied by their corresponding values on the factors from the original
      dynamic images for each frame, pure tissue dynamic images were obtained, from
      which arterial blood activities were excluded. Cluster analysis that averaged
      pixels having time-activity curves with the same shape was applied to pure tissue
      images to generate parametric MBF images. The usefulness of this method for
      quantifying regional MBF was evaluated using canine experiment data. H2(15)O PET
      scans and microsphere studies were performed on seven dogs at rest and after
      pharmacological stress. The image qualities and the contrast of parametric images
      obtained using the proposed method were significantly improved over either the
      tissue factor images or the parametric images obtained using a conventional
      method. Regional MBFs obtained using the proposed method correlated well with
      those obtained by the region of interest method (r = 0.94) and by the microsphere
      technique (r = 0.90). A non-invasive method is presented for generating
      parametric images of MBF from H2(15)O PET, using factor and cluster analysis.

PMID- 16411644
TI  - [Drug combinations and cardiovascular prevention].

PMID- 16411643
TI  - Design and validation of an analyser to measure sulphur hexafluoride gas during
      respiration.
AB  - The study presents the results of the development of an analyser to measure
      sulphur hexafluoride (SF6) gas in breathing circuits, for application is studies
      of lung function. The analyser consists of an in-line breathing circuit
      measurement transducer and a compact unit for signal treatment. The detector unit
      of the analyser consists of a near-infrared light source, a bandpass filter and a
      pyro-electrical detector. When incremental steps of SF6 gas between 0 and 2% were
      presented to the analyser, the maximum deviation from the theoretical calibration
      curve was calculated to be 0.01% SF6. The step response of the analyser (10-90%)
      was 250 ms. The sensitivity of the analyser to ambient temperature was 0.01% SF6
      degrees C(-1) in the range between 0 and 2% SF6. It is concluded that the
      analyser presented is accurate, and has a sufficient response speed to be used in
      clinical measurement settings. Furthermore, the analyser is resistant to changes
      in temperature, gas flow, orientation and movement, which are likely to occur in
      clinical measurement settings.

PMID- 16411645
TI  - [Prognosis at six months for primary care patients: prognostics factors
      analysis].
AB  - AIM OF THE SURVEY: The aim of the PREVENIR III study was to assess, in secondary
      prevention, the risk of subsequent coronary and cerebrovascular events at six
      months in a population of patients in private practice. METHODS: This was a
      prospective observational survey (6-month follow-up), including patients
      diagnosed with previous myocardial infarction, unstable angina or ischemic
      stroke, carried out by French general practitioners and cardiologists in private
      practice. RESULTS: 8288 patients were selected by 3746 physicians (2961 general
      practitioners and 785 cardiologists) representative of French metropolitan
      physicians in private practice. In this analysis the medical records of 6859
      coronary patients were analyzed. After a 6-month follow-up, 84 patients had been
      hospitalized for a subsequent coronary or cerebrovascular event (1.2%) i.e.
      cumulative incidence 3.1 event per 100 person-years (95% CI 2.4-3.8). In the
      coronary population 77.4% of the subsequent vascular events were coronary events
      and 22.6% were cerebrovascular events. The event rate of coronary events was 0.9%
      and the cumulative incidence 2.3 event per 100 person-years (95% CI 1.8-2.8), the
      risk of secondary ischemic stroke was 0.3% and the cumulative incidence 0.7 event
      per 100 person-years (95% CI 0.4-1.0), and the all-cause mortality rate was 1.0%
      and the cumulative incidence 2.5 event per 100 person-years (95% CI 1.9-3.1).
      61.0% of total death was cardiovascular deaths. Multivariate analysis showed that
      older age, recent index event, three vessel disease were more likely to undergo
      recurrent events. CONCLUSION: Our survey enabled a better understanding of the
      prognosis at six months for a large sample of coronary patients recruited in
      private practice medicine. For coronary patients treated in private practice the
      risk of subsequent events and total mortality is far from insignificant.

PMID- 16411646
TI  - [Prognosis at six months for coronary patients: impact of antiplatelet agents and
      statins].
AB  - PURPOSE: The aim of the PREVENIR III study was to assess, in secondary
      prevention, the risk after six months of subsequent coronary and cerebrovascular
      events. METHODS: A prospective observational survey, including patients diagnosed
      with previous myocardial infarction, unstable angina or ischemic stroke, was
      carried out by French general practitioners and cardiologists. RESULTS: 9556
      patients were selected by 3746 physicians representative of French physicians.
      The medical records of 6859 patients with previous unstable angina or myocardial
      infarction were analyzed. After a 6-month follow-up, 84 patients (1.2%) had been
      hospitalized for coronary or cerebrovascular event i.e. cumulative incidence 3.1
      per 100 person-years (95% CI 2.4-3.8) and 67 patients died (1.0%) i.e. 2.5 per
      100 person-years (95% CI 1.9-3.1). Patients treated with statins and antiplatelet
      agents were less likely to undergo subsequent vascular events (relative risk:
      0.35; 95% CI 0.20-0.61) than patients not receiving statins or antiplatelet
      agents. All-cause mortality rate decreased dramatically (relative risk: 0.32; 95%
      CI 0.16-0.65) in patients treated with a combination of statins and antiplatelet
      agents when compared to patients treated with neither statins nor antiplatelet
      agents. CONCLUSION: This work enabled a better understanding of the prognosis at
      six months in a large sample of coronary patients. We observed the beneficial
      impact of the combination of statins and antiplatelet agents in secondary
      prevention.

PMID- 16411647
TI  - [Reasons for the under-use of secondary prevention therapies in coronary patients
      over the age of 70 years].
AB  - INTRODUCTION: Although platelet antiaggregants, beta-blockers and statins have
      proved their efficacy as secondary prevention in all types of patients with
      arterial and thrombotic disease, these therapeutic categories remain under-used
      in the elderly. The reasons for this under-prescription are poorly understood.
      The aim of this study was to determine the reasons for not prescribing the
      principal secondary prevention therapies in elderly coronary patients. METHODS:
      Two transversal pharmaco-epidemiological surveys were carried out in a
      representative sample of French cardiologists. They included 1489 coronary
      patients aged 35 to 69 years and 1148 patients aged over 70 years, respectively.
      Risk factors, medical history, current treatments and reasons for non
      prescription of the principal therapies were collected. RESULTS: In subjects aged
      70 years or over, antiaggregants were not prescribed in 24% of patients, versus
      7.5% of younger patients. Statins were not prescribed in 37% of those over 70
      years, versus 14% of younger patients. Beta-blockers were not prescribed in 42%
      of elderly patients versus 23% of younger patients. ACE inhibitors were not
      prescribed in 57.6% of elderly subjects and 48.2% of younger subjects.
      Combinations of three or four secondary prevention treatments were half as
      frequently prescribed in patients over the age of 70. According to the
      physicians, the main reason for non-prescription in elderly patients was a lack
      of indication, which concerned 8% of the entire sample with respect to
      antiaggregants, 9% for beta-blockers and 14% for statins. These very high
      percentages were not found in younger subjects (1%, 3% and 2.5%, respectively).
      CONCLUSION: Our results confirm under-use of the principal secondary prevention
      therapies in elderly subjects, mainly because of a lack of indication, according
      to the physicians. In these patients, indications for secondary prevention appear
      to be tributary to numerous factors, such as age, the type of medical history,
      the availability of lipid parameters or compliance. In response to questions by
      practitioners, specific recommendations would be useful concerning secondary
      prevention in elderly coronary patients.

PMID- 16411648
TI  - [Combination therapy at hospital discharge in the USIC 2000 survey].
AB  - We tried to determine the prognostic impact of triple (antiplatelet agents,
      statins and beta-blockers) and quadruple (the same+ACE inhibitors) combination
      therapy at hospital discharge after acute myocardial infarction. The USIC 2000
      survey is nationwide registry of consecutive patients admitted to intensive care
      units for acute myocardial infarction in November 2000 in France. Of the 2119
      patients discharged alive, 1095 (52%) were prescribed a combination of
      antiplatelet agents, beta-blockers and statins (triple therapy), including 567
      (27%) with a similar combination plus ACE inhibitors (quadruple therapy). One
      year survival was 97% in patients receiving triple combination therapy versus 88%
      in those who received either no, one or two of these medications (p < 0.0001).
      After multivariate adjustment, the odds ratio for one-year mortality in patients
      with triple combination therapy was 0.49 (95% confidence interval: 0.32-0.75).
      Quadruple combination therapy had no additional predictive value in the entire
      population. In patients with ejection fraction < or = 35%, however, beta-blockers
      and ACE inhibitors were independent predictors of survival, and combination
      therapy had no additional prognostic value. CONCLUSIONS: compared with the
      prescription of any single class of secondary prevention medications, combination
      therapy offers additional protection in patients with acute myocardial
      infarction.

PMID- 16411649
TI  - [Changes in the prescription of cardiovascular prevention drugs in France between
      1995 and 2003: factors influencing the gap between evidence base medicine and
      clinical practice].
AB  - Dramatic progresses have occurred during the past 10 years in the field of
      cardiovascular secondary prevention. Many randomized trials have established the
      efficacy of statins, antiplatelet agents, beta-blockers and ACE inhibitors for
      reducing cardiovascular mortality, myocardial infarction and stroke in patients
      with coronary heart disease. Since 2002, American and European guidelines have
      emphasized the importance of optimal utilization of those four main therapeutic
      classes. Nevertheless, drugs prescription registries conducted in France since
      1995 revealed a persistent gap between evidence based medicine and clinical
      practice, only a minority of patient received an optimal treatment. Some factors
      associated with lower rate prescription have been identified: elderly patients,
      female gender, missing of LDL-cholesterol measurement, history of peripheral
      artery disease or stroke, and finally the difficulty of observance. At this time,
      optimization of management of these patients require a systematic measurement of
      LDL-cholestererol level for all patients with CAD, PAD or history of stroke, a
      larger prescription of statins in female patients and in elderly particularly for
      secondary prevention. Increasing observance which is the main challenge could
      involved the utilization of fixed drugs associations.

PMID- 16411650
TI  - Arsenic toxicology: five questions.

PMID- 16411652
TI  - Cytosolic and nuclear protein targets of thiol-reactive electrophiles.
AB  - Reactive electrophiles formed from toxic drugs and chemicals and by endogenous
      oxidative stress covalently modify proteins. Although protein covalent binding is
      thought to initiate a variety of adaptive and toxic responses, the identities of
      the protein targets are generally unknown, as are protein structural features
      that confer susceptibility to modification. We have analyzed the protein targets
      in nuclear and cytoplasmic proteomes from HEK293 cells treated in vitro with two
      biotin-tagged, thiol-reactive electrophiles, (+)-biotinyl-iodoacetamidyl-3, 6
      dioxaoctanediamine (PEO-IAB) and 1-biotinamido-4-(4'-[maleimidoethylcyclohexane]
      carboxamido)butane (BMCC). Biotinylated peptides were captured by affinity
      enrichment using neutravidin beads, and the adducted peptides were then analyzed
      by multidimensional liquid chromatography-tandem mass spectrometry. A total of
      897 adducts were mapped to different cysteine residues in 539 proteins. Adduction
      was selective and reproducible, and > 90% of all adducted proteins were modified
      at only one or two sites. A core group of 125 cysteines (14% of the total) was
      consistently modified by both electrophiles. Selective modification of several
      protein domain structures and motifs indicates that certain protein families are
      particularly susceptible to alkylation. This approach can be extended to studies
      of other protein-damaging oxidants and electrophiles and can provide new insights
      into targets and consequences of protein damage in toxicity and disease.

PMID- 16411651
TI  - The 5'-GNC site for DNA interstrand cross-linking is conserved for diepoxybutane
      stereoisomers.
AB  - The bifunctional alkylating agent 1,2,3,4-diepoxybutane forms interstrand DNA-DNA
      cross-links between the N7 positions of deoxyguanosine residues on opposite
      strands of the duplex. For racemic diepoxybutane, these cross-links predominate
      within 5'-GNC/3'CNG sequences, where N is any nucleotide. We used denaturing
      polyacrylamide gel electrophoresis (dPAGE) to examine the role of stereochemistry
      in the cross-linking reaction, subjecting a restriction fragment to cross-linking
      with S,S-DEB, R,R-DEB, or meso-DEB. DNA cross-links generated by each isomer were
      isolated by dPAGE, and the sites of cross-linking were identified by sequencing
      gel analysis of DNA fragments generated by hot piperidine cleavage. We found that
      the 5'-GNC consensus sequence of racemic DEB is conserved, but the efficiencies
      of cross-linking vary, with S,S- > R,R- > meso-DEB. These results help explain
      the observed differences between the biological activities of DEB stereoisomers.

PMID- 16411653
TI  - Molecular cloning and expression of a novel cytochrome p450 from turkey liver
      with aflatoxin b1 oxidizing activity.
AB  - Cytochromes P450 are members of a superfamily of oxidative hemoprotein enzymes
      that metabolize a variety of endogenous and exogenous compounds. Previous studies
      in our laboratory have shown that efficient P450-mediated activation underlies
      the extreme sensitivity of poultry, specifically turkeys, to the toxic effects of
      the mycotoxin aflatoxin B1 (AFB1). Using 3'- and 5'-rapid amplification of cDNA
      ends (RACE), we amplified from turkey liver RNA a full-length 1.73 kb cDNA
      predicted to be 528 amino acids with 94.7% sequence identity to a CYP1A5 from
      chicken liver. A truncated construct of the turkey CYP1A5 gene with 29 amino
      acids deleted from the hydrophobic NH2-terminal region was cloned and
      heterologously expressed in Escherichia coli. The expressed protein from E. coli
      membranes had a CO-binding spectrum typical of P450s, and it catalyzed the O
      dealkylation of the CYP1A prototype substrates ethoxyresorufin and
      methoxyresorufin. CYP1A5-mediated O-dealkylation of methoxyresorufin was
      completely inhibited by alpha-naphthoflavone, a specific CYP1A inhibitor.
      Inhibitors to other mammalian P450s (3A4, 2D, 2E, and 3A1) either slightly
      inhibited this activity or not at all. CYP1A5 oxidized AFB1 to form two
      metabolites: the reactive intermediate, AFB1 -8,9-epoxide (AFBO), and aflatoxin
      M1 (AFM1). Because of the importance of AFBO and AFM1 in the toxicity of AFB1, we
      conclude that this P450 probably plays some role in the well-known
      hypersensitivity of turkeys to AFB1. To our knowledge, this is the first P450
      cloned and sequenced from turkeys, the species in which the toxicity of AFB1 was
      first discovered.

PMID- 16411654
TI  - Substrate specificity of rabbit aldehyde oxidase for nitroguanidine and
      nitromethylene neonicotinoid insecticides.
AB  - The nitroguanidine or nitromethylene moiety of the newest major class of
      insecticides, the neonicotinoids, is important for potency at insect nicotinic
      receptors and selectivity relative to mammalian receptors. Aldehyde oxidase (AOX)
      was recently identified as the imidacloprid nitroreductase of mammalian liver,
      producing both nitrosoguanidine and aminoguanidine metabolites. The present study
      considers the ability of AOX, partially purified from rabbit liver, to reduce
      five commercial nitroguanidine (i.e., imidacloprid, thiamethoxam, clothianidin,
      and dinotefuran) and nitromethylene (i.e., nitenpyram) neonicotinoid insecticides
      and three derivatives thereof (i.e., the N-methyl and nitromethylene analogues of
      imidacloprid and desmethylthiamethoxam). LC/MS/MS was used to demonstrate that
      AOX reduces nitroguanidines to both nitroso- and aminoguanidines, while
      nitromethylenes are reduced only to the corresponding nitroso metabolites.
      Additionally, nitrosonitenpyram was found to spontaneously dehydrate to form a 2
      cyanoamidine metabolite, mimicking a predominant photoreaction. The substrate
      specificity of AOX was characterized as follows: Neonicotinoids with a tertiary
      nitrogen (N-methylimidacloprid and thiamethoxam) are poor substrates;
      nitroguanidines are metabolized faster than nitromethylenes; and clothianidin is
      the most rapidly reduced. Kinetic constants were measured for reduction of three
      nitroguanidines at two concentrations of AOX. At 2 mg protein/mL, only nitroso
      metabolites were detected, with Km values of 1.03, 2.99, and 2.41 mM and Vmax
      values of 5.13, 2.54, and 0.98 nmol/min/mg protein measured for clothianidin,
      imidacloprid, and dinotefuran, respectively. At 5 mg protein/mL, both amino and
      nitroso metabolites were detected. However, with each nitroguanidine, the
      formation of nitroso metabolites did not saturate at substrate levels up to 4 mM,
      whereas amino metabolite formation exhibited Km values of 0.052, 0.16, and 0.084
      mM with corresponding Vmax values of 0.80, 1.24, and 0.79 nmol/min/mg protein for
      clothianidin, imidacloprid, and dinotefuran, respectively. These in vitro
      observations show large structural differences in the rates of AOX-catalyzed
      reduction and help to interpret the extensive studies on in vivo metabolism of
      neonicotinoid insecticides.

PMID- 16411655
TI  - Quantitative analysis and chronic dosimetry of the aflatoxin B1 plasma albumin
      adduct Lys-AFB1 in rats by isotope dilution mass spectrometry.
AB  - Aflatoxin B1 (AFB1) is a major risk factor in the pathogenesis of liver cancer in
      Asia and sub-Saharan Africa. Biomarkers reflecting exposure will facilitate
      disease risk assessment and the efficacy of protective interventions in these
      populations. The Lys-AFB1 adduct in plasma albumin is a candidate biomarker for
      this role. Although aflatoxin albumin adducts are most frequently measured in
      epidemiological studies using an enzyme-linked immunosorbent assay, a more
      specific and 10-fold more sensitive isotopic dilution mass spectrometric assay
      for Lys-AFB1 has recently become available. Here, the dosimetry of chronically
      administered AFB1 at lower doses than have been previously studied was explored
      using this assay. AFB1 was administered to rats for nine consecutive days at
      eight dose levels ranging from 50 pg to 55 microg/kg body wt. Plasma samples were
      enzymatically digested and processed by solid phase extraction. Lys-AFB1 was
      isolated by HPLC and detected via selected reaction monitoring. The dose-response
      relationship was linear-quadratic exhibiting upward curvature at higher doses.
      The adduct yield [(pg Lys-AFB1/mg albumin)/(microg AFB1/kg body wt)] increased
      nonlinearly with the dose by 6-fold between the 0.05 and 55 microg AFB1/kg body
      wt groups and exhibited the onset of saturation in the highest dose group where
      the adduct yield was approximately 2%. Incomplete knowledge of the timing of
      exposure and the complexity of the underlying biology confound the precise
      determination of prior AFB1 exposures in humans; however, the dosimetry of AFB1
      observed in chronically dosed rats conceptually suggests that measurements in
      humans may underestimate exposure if a constant fraction of the AFB1 dose,
      approximately 2%, is assumed to be converted to Lys-AFB1 without regard to the
      dose.

PMID- 16411656
TI  - Relatively small increases in the steady-state levels of nucleobase deamination
      products in DNA from human TK6 cells exposed to toxic levels of nitric oxide.
AB  - Nitric oxide (NO) is a physiologically important molecule that has been
      implicated in the pathophysiology of diseases associated with chronic
      inflammation, such as cancer. While the complicated chemistry of NO-mediated
      genotoxicity has been extensively study in vitro, neither the spectrum of DNA
      lesions nor their consequences in vivo have been rigorously defined. We have
      approached this problem by exposing human TK6 lymphoblastoid cells to controlled
      steady-state concentrations of 1.75 or 0.65 microM NO along with 186 microM O2 in
      a recently developed reactor that avoids the anomalous gas-phase chemistry of NO
      and approximates the conditions at sites of inflammation in tissues. The
      resulting spectrum of nucleobase deamination products was defined using a
      recently developed liquid chromatography/mass spectrometry (LC/MS) method, and
      the results were correlated with cytotoxicity and apoptosis. A series of control
      experiments revealed the necessity of using dC and dA deaminase inhibitors to
      avoid adventitious formation of 2'-deoxyuridine (dU) and 2'-deoxyinosine (dI),
      respectively, during DNA isolation and processing. Exposure of TK6 cells to 1.75
      microM NO and 186 microM O2 for 12 h (1260 microM x min dose) resulted in 32%
      loss of cell viability measured immediately after exposure and 87% cytotoxicity
      after a 24 h recovery period. The same exposure resulted in 3.5-, 3.8-, and 4.1
      fold increases in dX, dI, and dU, respectively, to reach the following levels:
      dX, 7 (+/- 1) per 10(6) nt; dI, 25 (+/- 2.1) per 10(6) nt; and dU, 40 (+/- 3.8)
      per 10(6) nt. dO was not detected above the limit of detection of 6 lesions per
      10(7) nt in 50 microg of DNA. A 12 h exposure to 0.65 microM NO and 190 microM O2
      (468 microM x min dose) caused 1.7-, 1.8-, and 2.0-fold increases in dX, dI, and
      dU, respectively, accompanied by a approximately 15% (+/- 3.6) reduction in cell
      viability immediately after exposure. Again, dO was not detected. These results
      reveal modest increases in the steady-state levels of DNA deamination products in
      cells exposed to relatively cytotoxic levels of NO. This could result from
      limited nitrosative chemistry in nuclear DNA in cells exposed to NO or high
      levels of formation balanced by rapid repair of nucleobase deamination lesions in
      DNA.

PMID- 16411657
TI  - N-Nitroso products from the reaction of indoles with Angeli's salt.
AB  - While nitroxyl (HNO) has been shown to engage in oxidation and hydroxylation
      reactions, little is known about its nitrosating potential. We therefore sought
      to investigate the kinetics of formation and identity of the reaction products of
      the classical nitroxyl donor Angeli's salt (AS) with three representative
      tryptophan derivates (melatonin, indol-3-acetic acid, and N-acetyl-l-tryptophan)
      in vitro. In the presence of oxygen and at physiological pH, we find that the
      major products generated are the corresponding N-nitrosoindoles with negligible
      formation of oxidation and nitration products. A direct comparison of the effects
      of AS, nitrite, peroxynitrite, aqueous NO* solution, and the NO-donor DEA/NO
      toward melatonin revealed that nitrite does not participate in the reaction and
      that peroxynitrite is not an intermediate. Rather, N-nitrosoindole formation
      appears to proceed via a mechanism that involves electrophilic attack of HNO on
      the indole nitrogen, followed by a reaction of the intermediary hydroxylamine
      derivative with oxygen. Further in vivo experiments demonstrated that AS exhibits
      a unique nitrosation signature which differs from that of DEA/NO inasmuch as
      substantial amounts of a mercury-resistant nitroso species are generated in the
      heart, whereas S-nitrosothiols are the major reaction products in plasma. These
      data are consistent with the notion that the generation of nitroxyl in vivo gives
      rise to formation of nitrosative post-translational protein modifications in the
      form of either S- or N-nitroso products, depending on the redox environment. It
      is intriguing to speculate that the particular efficiency of nitroxyl to form N
      nitroso species in the heart may account for the positive inotropic effects
      observed with AS earlier.

PMID- 16411658
TI  - Competing roles of aldo-keto reductase 1A1 and cytochrome P4501B1 in
      benzo[a]pyrene-7,8-diol activation in human bronchoalveolar H358 cells: role of
      AKRs in P4501B1 induction.
AB  - Benzo[a]pyrene (BP) requires metabolic activation to electrophiles to exert its
      deleterious effects. We compared the respective roles of aldo-keto reductase 1A1
      (AKR1A1, aldehyde reductase) and P4501B1 in the formation of BP-7,8-dione and BP
      tetrols, respectively, in intact bronchoalveolar cells manipulated to express
      either enzyme. Metabolite formation was confirmed by HPLC/MS and quantitatively
      measured by HPLC/UV/beta-RAM. In TCDD-treated H358 cells (P4501B1 expression),
      the anti-BPDE hydrolysis product BP-tetrol-1 increased over 3-12 h to a constant
      level. In H358 AKR1A1 transfectants, formation of BP-7,8-dione was elevated for 3
      12 h but significantly decreased after 24 h. Interestingly, BP-tetrols were also
      detected in AKR1A1 transfectants even though they do not constitutively express
      P4501A1/P4501B1 enzymes. Northern and Western blotting confirmed the induction of
      P4501B1 by BP-7,8-dione in parental cells and the induction of P4501B1 by BP-7,8
      diol in AKR1A1-transfected cells. P4501B1 induction was blocked in AKR1A1
      transfectants by the AKR1A1 inhibitor (sulfonylnitromethane), the o-quinone
      scavenger (N-acetyl-l-cysteine), or the cytosolic AhR antagonist (diflubenzuron).
      Attenuation of P4501B1 induction in these cells was verified by measuring a
      decrease in BP-tetrol formation. Our studies show that the formation of BP-7,8
      dione by AKR1A1 in human bronchoalveolar cells leads to an induction of P4501B1
      and that a functional consequence of this induction is elevated anti-BPDE
      production as detected by increased BP-tetrol formation. Therefore, the role of
      AKR1A1 in the activation of BP-7,8-diol is bifunctional; that is, it directly
      activates BP-7,8-diol to the reactive and redox-active PAH o-quinone (BP-7,8
      dione) and it indirectly trans-activates the P4501B1 gene by generating the aryl
      hydrocarbon receptor (AhR) ligand BP-7,8-dione.

PMID- 16411659
TI  - The L-type calcium channel blockers, hantzsch 1,4-dihydropyridines, are not
      peroxyl radical-trapping, chain-breaking antioxidants.
AB  - The antioxidant properties of Hantzsch 1,4-dihydropyridine esters and two dibenzo
      1,4-dihydropyridines, 9,10-dihydroacridine (DHAC) and N-methyl-9,10
      dihydroacridine (N-Me-DHAC), have been explored by determining whether they
      retard the autoxidation of styrene or cumene at 30 degrees C. Despite a claim to
      the contrary [(2003) Chem. Res. Toxicol. 16, 208-215], the Hantsch esters were
      found to be virtually inactive as chain-breaking antioxidants (CBAs), their
      reactivity toward peroxyl radicals being some 5 orders of magnitude lower than
      that of the excellent CBA, 2,2,5,7,8-pentamethyl-6-hydroxy-chroman (PMHC). DHAC
      was found to be about a factor of 10 less reactive than PMHC. From kinetic
      measurements using DHAC, N-deuterio-DHAC, and N-Me-DHAC, it is concluded that it
      is the N--H hydrogen in DHAC that is abstracted by peroxyl radicals, despite the
      fact that in DHAC the calculated C-H bond dissociation enthalpy (BDE) is about 11
      kcal/mol lower than the N-H BDE. The rates of hydrogen atom abstraction by the
      2,2-diphenyl-1-picrylhydrazyl radical (dpph*) have also been determined for the
      same series of compounds. The trends in the peroxyl and dpph* rate constants are
      similar.

PMID- 16411660
TI  - Mode of action of poly(vinylpyridine-N-oxide) in preventing silicosis: effective
      scavenging of carbonate anion radical.
AB  - Small particles of crystalline silicon dioxide (crystallites) are exceptionally
      toxic. Inhalation of quartz crystallites causes silicosis, a devastating lung
      disease afflicting miners, particularly coal and stone workers.
      Poly(vinylpyridine-N-oxide)s (PVPNOs) have been applied in the prevention and
      treatment of silicosis, but their mode of action has been obscure. Recently, the
      sites of inducible *NO synthase activation and of nitrotyrosine formation were
      associated anatomically with the pathological quartz particle-caused lesions in
      the lungs. It has been suggested that the *NO formed combines rapidly with O2*-
      to yield ONOO-, a potential mediator of lung injury following silica exposure.
      Here, we show that PVPNOs do not react with peroxynitrite but scavenge
      exceptionally rapidly CO3*- radicals, which are produced in the decomposition of
      ONOO- in bicarbonate solutions. The rate constant for the reaction of CO3*- with
      PVPNO was found to be independent of the type and size of PVPNO, i.e., k = (1.9
      +/- 0.2) x 10(5) M(-1) s(-1) per monomer. In contrast, the rate constant for the
      reaction of CO3*- with the small molecule 4-methylpyridine N-oxide did not exceed
      1 x 10(4) M(-1) s(-1). The underlying reason for the difference is that, in the
      dissolved polymeric PVPNOs, the electrostatic repulsion between the N-oxide
      zwitterions destabilizes them, increasing dramatically their pKa. The protonated
      N-oxides at physiological pH have abstractable hydrogen atoms and are expected to
      react rapidly with CO3*-, just as cyclic hydroxylamines do. It is also shown that
      PVPNO inhibits tyrosine nitration by peroxynitrite at pH 7.6 in the presence of
      excess of CO2 in a concentration-dependent manner. Hence, binding of PVPNO to the
      quartz particles and eliminating CO3*- could prevent the killing of macrophages,
      the associated release of macrophage-recruiting cytokines, and the amplification
      of the local concentration of *NO by the recruited macrophages. The latter causes
      necrosis of the macrophage-infiltrated lung tissue and, upon repair of the
      necrotic lesion, results in the growth of the dysfunctional fibrotic tissue,
      which is the hallmark of silicosis.

PMID- 16411661
TI  - Structure-activity relationship for noncoplanar polychlorinated biphenyl
      congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1).
AB  - Ryanodine receptor isoforms are expressed in both excitable and nonexcitable
      tissues where they form microsomal Ca2+ release channels broadly involved in
      shaping cellular signaling. In this report, we provide a detailed structure
      activity relationship (SAR) for polychlorinated biphenyl (PCB) congeners and
      metabolites necessary for enhancing ryanodine receptor type 1 (RyR1) activity
      using [3H]ryanodine ([3H]Ry) binding analysis. The 2,3,6-Cl PCB configuration is
      most important for optimal recognition by the RyR1 complex and/or critical for
      sensitizing its activation. Para substitution(s) diminishes the activity with
      para-chloro having a higher potency than the corresponding para-hydroxy
      derivative. The addition of a more bulky para-methyl-sulfonyl group eliminates
      the activity toward RyR1, supporting the importance of the para positions in
      binding RyR1. The requirement for an intact major T cell immunophilin FKBP12-RyR1
      complex was observed with each of 12 active PCB congeners indicating a common
      mechanism requiring an immunophilin-regulated Ca2+ release channel. An excellent
      correlation between the relative potencies for doubling [3H]Ry binding and the
      corresponding initial rates of PCB-induced Ca2+ efflux indicates that [3H]Ry
      binding analysis provides a measure of dysregulation of microsomal Ca2+
      transport. The SAR for activating RyR1 is consistent with those previously
      reported in several in vivo and in vitro studies, suggesting that a common
      mechanism may contribute to the toxicity of noncoplanar PCBs. A practical
      application of the receptor-based screen developed here with RyR1 is that it
      provides a quantitative SAR that may be useful in predicting biological activity
      and risk of mixtures containing noncoplanar PCB congeners that have low or a lack
      of aryl hydrocarbon receptor activity.

PMID- 16411662
TI  - Inhibition of human mitochondrial aldehyde dehydrogenase by 4-hydroxynon-2-enal
      and 4-oxonon-2-enal.
AB  - Previous studies found the lipid peroxidation product 4-hydroxynon-2-enal (4HNE)
      to be both a substrate and an inhibitor of mitochondrial aldehyde dehydrogenase
      (ALDH2). Inhibition of the enzyme by 4HNE was demonstrated kinetically to be
      reversible at low micromolar aldehyde but may involve covalent modification at
      higher concentrations. Structurally analogous to 4HNE is the lipid peroxidation
      product 4-oxonon-2-enal (4ONE), which is more reactive than 4HNE toward protein
      nucleophiles. The goal of this work was to determine whether 4ONE is a substrate
      or inhibitor of human ALDH2 (hALDH2) and elucidate the mechanism of enzyme
      inhibition by 4HNE and 4ONE. Both 4ONE and its glutathione conjugate were found
      to be substrates for the enzyme in the presence of NAD. At low concentrations of
      4ONE (< or = 10 microM), hALDH2 catalyzed the oxidation of 4ONE to 4-oxonon-2
      enoic acid (4ONEA) with a maximal yield of 5.2 mol 4ONEA produced per mol of
      enzyme (monomer). However, subsequent analysis of hALDH2 activity toward
      propionaldehyde revealed that both 4ONE and the oxidation product, 4ONEA, were
      potent, irreversible inhibitors of the enzyme. In contrast, inhibition of hALDH2
      by a high concentration of 4HNE (i.e., 50 microM) was primarily reversible. The
      reactivity of 4ONEA toward glutathione was measured and found to be comparable to
      that of 4HNE, indicating that the 4ONE-oxidation product is a reactive
      electrophile. hALDH2/NAD was incubated with 4HNE, 4ONE, and 4ONEA, and mass
      spectral analysis of tryptic peptides revealed covalent modification of an hALDH2
      active site peptide by both 4ONE and 4ONEA. These data demonstrate that hALDH2
      catalyzes the oxidation of 4ONE to 4ONEA; however, the product 4ONEA is a
      reactive electrophile. Furthermore, both 4ONE and 4ONEA are potent, irreversible
      inhibitors of the enzyme.

PMID- 16411663
TI  - Human cytochrome p450 enzymes of importance for the bioactivation of
      methyleugenol to the proximate carcinogen 1'-hydroxymethyleugenol.
AB  - In vitro studies were performed to elucidate the human cytochrome P450 enzymes
      involved in the bioactivation of methyleugenol to its proximate carcinogen 1'
      hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450
      enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19, and 2D6 are
      intrinsically able to 1'-hydroxylate methyleugenol. An additional experiment with
      Gentest microsomes, expressing the same individual enzymes to roughly average
      liver levels, indicated that P450 1A2, 2C9, 2C19, and 2D6 contribute to
      methyleugenol 1'-hydroxylation in the human liver. A study, in which correlations
      between methyleugenol 1'-hydroxylation in human liver microsomes from 15
      individuals and the conversion of enzyme specific substrates by the same
      microsomes were investigated, showed that P450 1A2 and P450 2C9 are important
      enzymes in the bioactivation of methyleugenol. This was confirmed in an
      inhibition study in which pooled human liver microsomes were incubated with
      methyleugenol in the presence and absence of enzyme specific inhibitors. Kinetic
      studies revealed that at physiologically relevant concentrations of methyleugenol
      P450 1A2 is the most important enzyme for bioactivation of methyleugenol in the
      human liver showing an enzyme efficiency (kcat/Km) that is approximately 30, 50,
      and > 50 times higher than the enzyme efficiencies of, respectively, P450 2C9,
      2C19, and 2D6. Only when relatively higher methyleugenol concentrations are
      present P450 2C9 and P450 2C19 might contribute as well to the bioactivation of
      methyleugenol in the human liver. A 5-fold difference in activities was found
      between the 15 human liver microsomes of the correlation study (range, 0.89-4.30
      nmol min(-1) nmol P450(-1)). Therefore, interindividual differences might cause
      variation in sensitivity toward methyleugenol. Especially lifestyle factors such
      as smoking (induces P450 1A) and the use of barbiturates (induces P450 2C) can
      increase the susceptibility for adverse effects of methyleugenol.

PMID- 16411664
TI  - Noncovalent DNA binding and the mechanism of oxidative DNA damage by fecapentaene
      12.
AB  - The fecapentaenes are a group of mutagenic, polyunsaturated lipids that are
      produced endogenously in the human gastrointestinal tract. Previous studies show
      that the fecapentaenes cause oxidative DNA damage, but the chemical mechanisms by
      which this occurs remain unclear. The data presented here indicate that
      fecapentaene-12 causes direct oxidative DNA damage via production of the reactive
      oxygen species O2*-, H2O2, and HO*. In addition, evidence is presented indicating
      that fecapentaene-12 associates noncovalently with duplex DNA. Fecapentaene-12
      provides an interesting new example highlighting the potential for hydrophobic
      long chain hydrocarbons to associate noncovalently with duplex DNA.

PMID- 16411665
TI  - Mass spectroscopic characterization of protein modification by malondialdehyde.
AB  - Malondialdehyde (MDA), a naturally occurring dialdehyde produced in the membrane
      by lipid peroxidation, is a strong alkylating agent of primary amino groups. We
      recently raised a monoclonal antibody (mAb1F83) directed to the lipofuscin-like
      MDA--lysine adduct and demonstrated the presence of immunoreactivity to the
      antibody in the atherosclerotic lesions, in which intense positivity was
      associated primarily with macrophage-derived foam cells (Yamada et al., (2001) J.
      Lipid Res. 42, 1187-1196). To identify the structure of the epitope in the
      protein recognized by mAb1F83, in the present study, we exposed chain B from
      bovine insulin (insulin B chain) to MDA and characterized the MDA adducts by mass
      spectrometry. The MDA-modified insulin B chain was digested with V8 protease, and
      the resulting peptides were subjected to liquid chromatography--electrospray
      ionization--mass spectrometry (LC--ESI--MS/MS). The MS/MS analyses confirmed the
      formation of N-propenal- (+54 Da) and dihydropyridine-type (DHP, +134 Da) adducts
      in both Lys29 and the N-terminus of insulin B chain. The ELISA analysis of HPLC
      fractions of peptides, including the DHP adducts using mAb1F83, showed that the
      immunoreactivity of the DHP--lysine adduct was more significant than the DHP--N
      terminus adduct. The results of this study chemically characterized that the MDA
      adducts such as DHP-type adducts generated in the epsilon-amino group of lysine
      and N-terminal amino acid residues in the protein and the structure of the
      epitope recognized by mAb1F83 were DHP--lysine adducts in protein.

PMID- 16411666
TI  - Identification of 4-oxo-2-hexenal and other direct mutagens formed in model lipid
      peroxidation reactions as dGuo adducts.
AB  - We searched for mutagens that react with 2'-deoxyguanosine (dGuo) in model
      systems of lipid peroxidation. To autoxidation systems of methyl linoleate (model
      of omega-6 fat), methyl alpha-linolenate (MLN) (model of omega-3 fat), and
      commercial salad oil, dGuo was added. The reaction mixtures were analyzed by
      HPLC. Six adducts were detected, and their structures were determined by 1H and
      13C NMR, UV, and mass spectra and by comparison with synthetic authentic samples.
      The mutagens that reacted with dGuo to form these adducts were proposed as
      glyoxal, glyoxylic acid, ethylglyoxal, and 4-oxo-2-hexenal (4-OHE). The formation
      of 8-hydroxy-dGuo, an oxidized product of dGuo, was also detected in the model
      reaction mixtures. Among them, glyoxal and glyoxylic acid are known mutagens,
      while ethylglyoxal and 4-OHE, produced from MLN, have not been reported as
      mutagens thus far. We confirmed the mutagenic activity of 4-OHE with Salmonella
      strains, TA100 and TA104, without S9 mix. These compounds may be involved in
      lipid peroxide-related cancers.

PMID- 16411667
TI  - Activation of carboplatin by carbonate.
AB  - Carboplatin, [Pt(NH3)2(CBDCA-O,O')], 1, where CBDCA is cyclobutane-1,1
      dicarboxylate, is in wide clinical use for the treatment of ovarian, lung, and
      other types of cancer. Because carboplatin is relatively unreactive toward
      nucleophiles, an important question concerning the drug is the mechanism by which
      it is activated in vivo. Using [1H,15N] heteronuclear single quantum coherance
      spectroscopy (HSQC) NMR and 15N-labeled carboplatin, we show that carboplatin
      reacts with carbonate ion in carbonate buffer to produce ring-opened products,
      the nature of which depends on the pH of the medium. The assignment of HSQC NMR
      resonances was facilitated by studying the reaction of carboplatin in strong
      acid, which also produces a ring-opened product. The HSQC NMR spectra and UV
      visible difference spectra show that reaction of carboplatin with carbonate at pH
      > 8.6 produces mainly cis-[Pt(NH3)2(CO3(-2))(CBDCA-O)]-2, 5, which contains the
      mono-dentate CBDCA ligand and mono-dentate carbonate. At pH 6.7, the primary
      product is the corresponding bicarbonato complex, which may be in equilibrium
      with its decarboxylated hydroxo analogue. The UV-visible absorption data indicate
      that the pKb for the protonation of 5 is approximately 8.6. Thus, the reaction of
      carboplatin with carbonate produces a mixture of ring-opened species that are
      anions at physiological pH. HSQC NMR studies on 15N-labeled carboplatin in RPMI
      culture media containing 10% fetal bovine serum with and without added carbonate
      suggest that carbonate is the attacking nucleophile in culture media. However,
      because the rate of reaction of carbonate with carboplatin at physiological pH is
      small, NMR peaks for ring-opened carboplatin were not detected with HSQC NMR. The
      rate of disappearance of carboplatin in culture medium containing 9 x 10(8)
      Jurkat cells is essentially the same as that in carbonate buffer, indicating that
      the ring-opening reaction is not affected by the presence of cells. This work
      shows that carbonate at concentrations found in culture media, blood, and the
      cytosol readily displaces one arm of the CBDCA ligand of carboplatin to give a
      ring-opened product, which at physiological pH is a mixture of anions. These ring
      opened species may be important in the uptake, antitumor properties, and toxicity
      of carboplatin.

PMID- 16411668
TI  - Reaction of the tobacco alkaloid myosmine with hydrogen peroxide.
AB  - Myosmine is not only one of the minor tobacco alkaloids but is also present in
      various foods. Therefore, research on myosmine metabolism and activation has been
      intensified. 3-Pyridylacetic acid, 4-oxo-4-(3-pyridyl)butanoic acid (keto acid),
      3-pyridylmethanol, 3'-hydroxymyosmine, and 4-hydroxy-1-(3-pyridyl)-1-butanone
      (HPB) have been identified as urinary metabolites after oral administration to
      female Wistar rats. Although N-nitrosation of myosmine, yielding N'
      nitrosonornicotine (NNN) and HPB, was considered as a possible in vivo activation
      route, the formation pathways of most metabolites could not be explained until
      now. Therefore, under consideration of its high reactivity due to its imine
      structure, peroxidation of myosmine seemed to be a promising additional
      activation pathway. In vitro peroxidation using myosmine (8.9 micromol in 200
      microL methanol) with a mixture of hydrogen peroxide (57.6 micromol, 5 microL of
      a 35% solution) and acetic acid anhydride (106 micromol, 10 microL) already
      showed high yields of reaction products after 30 min ultrasonic treatment. The
      product pattern was analyzed by HPLC/UV and GC/MS. Besides unchanged myosmine, 3
      pyridylacetic acid, keto acid, 3-pyridylmethanol, HPB, and nornicotyrine have
      been identified as myosmine peroxidation products. Different product patterns
      were obtained after 24 h and 4 days due to a time-dependent degradation,
      formation, and conversion of the reaction products. Therefore, peroxidation
      reaction of myosmine might explain the in vivo formation of 3-pyridylacetic acid,
      keto acid, 3-pyridylmethanol, and HPB in rats. In addition, because of
      acetylating conditions using acetic acid anhydride, N-(4-oxo-4-pyridin-3-yl
      butyl)acetamide was rapidly formed during the first 30 min of the reaction.

PMID- 16411669
TI  - In vitro phototoxicity of phenothiazines: involvement of stable UVA photolysis
      products formed in aqueous medium.
AB  - This paper reports the results of an in vitro evaluation of the phototoxic
      potential of stable photoproducts formed by UVA photolysis of three
      phenothiazines, perphenazine, fluphenazine, and thioridazine, in a water
      environment. Perphenazine gave a single product due to dechlorination. From
      thioridazine, the two major products formed; the endocyclic sulfoxide and the
      endocyclic N-oxide in which the 2-SCH3 substituent was replaced by a hydroxy
      group were tested. From fluphenazine, two products have been examined as follows:
      an exocyclic N-piperazine oxide and a carboxylic acid arising from hydrolysis of
      the 2-CF3 group. The phototoxicity of the isolated photoproducts has been studied
      in order to determine their possible involvement in the photosensitizing effects
      exhibited by the parent drugs, using hemolysis and 3T3 fibroblasts viability as
      in vitro assays. As fluphenazine, perphenazine, and thioridazine did, some
      photoproducts proved phototoxic. In particular, the perphenazine dechlorinated
      photoproduct and the thioridazine N-oxide were found to exert phototoxic
      properties similar to the parent compounds. Therefore, our data suggest that some
      phenothiazine photoproducts may play a role in the mechanism of photosensitivity
      of these drugs. Because some of these photoproducts correspond to metabolic
      products of phenothiazines found in humans, it cannot be ruled out that
      metabolites of phenothiazines can be phototoxic in vivo.

PMID- 16411671
TI  - Improved synthetic route to n-B18H22.
AB  - Simple iodine oxidation of the B(9)H(12)(-) anion in toluene at room temperature
      reliably gives excellent yields ( approximately 80%) of n-B(18)H(22) (anti
      B(18)H(22)) and thus provides a convenient, large-scale, safe route to this
      important polyborane cluster.

PMID- 16411670
TI  - The greater reactivity of estradiol-3,4-quinone vs estradiol-2,3-quinone with DNA
      in the formation of depurinating adducts: implications for tumor-initiating
      activity.
AB  - Strong evidence supports the idea that specific metabolites of estrogens, mainly
      catechol estrogen-3,4-quinones, can react with DNA to become endogenous
      initiators of breast, prostate, and other human cancers. Oxidation of the
      catechol estrogen metabolites 4-hydroxyestradiol (4-OHE2) and 2-OHE2 leads to the
      quinones, estradiol-3,4-quinone (E2-3,4-Q) and estradiol-2,3-quinone (E2-2,3-Q),
      respectively. The reaction of E2-3,4-Q with DNA affords predominantly the
      depurinating adducts 4-OHE2-1-N3Ade and 4-OHE2-1-N7Gua, whereas the reaction of
      E2-2,3-Q with DNA yields the newly synthesized depurinating adduct 2-OHE2-6
      N3Ade. The N3Ade adducts are lost from DNA by rapid depurination, while the N7Gua
      adduct is lost from DNA with a half-life of approximately 3 h at 37 degrees C. To
      compare the relative reactivity of E2-3,4-Q and E2-2,3-Q, the compounds were
      reacted individually with DNA for 0.5-20 h at 37 degrees C, as well as in
      mixtures (3:1, 1:1, 1:3, and 5:95) for 10 h at 37 degrees C. Depurinating and
      stable adducts were analyzed. In similar experiments, the relative reactivity of
      4-OHE2 and 2-OHE2 with DNA was determined after activation by lactoperoxidase,
      tyrosinase, prostaglandin H synthase (PHS), or 3-methylcholanthrene-induced rat
      liver microsomes. Starting with the quinones, the levels of depurinating adducts
      formed from E2-3,4-Q were much higher than that of the depurinating adduct from
      E2-2,3-Q. Similar results were obtained with lactoperoxidase or tyrosinase
      catalyzed oxidation of 4-OHE2 and 2-OHE2, whereas with activation by PHS or
      microsomes, a relatively higher amount of the depurinating adduct from E2-2,3-Q
      was detected. These results demonstrate that the E2-3,4-Q is much more reactive
      with DNA than E2-2,3-Q. The relative reactivities of E2-3,4-Q and E2-2,3-Q to
      form depurinating adducts correlate with the carcinogenicity, mutagenicity, and
      cell-transforming activity of their precursors, the catechol estrogens 4-OHE2 and
      2-OHE2. This is essential information for understanding the cancer risk posed by
      oxidation of the two catechol estrogens.

PMID- 16411673
TI  - First structural determination of a trivalent californium compound with oxygen
      coordination.
AB  - Single crystals of Cf(IO(3))(3) (1) were synthesized by the hydrothermal reaction
      of CfCl(3) and H(5)IO(6), and the structure was determined with single-crystal X
      ray diffraction. This structural determination of 1 represents the first for a
      trivalent californium compound containing oxygen coordination. This compound has
      been further characterized with the use of Raman spectroscopy and emission
      spectroscopy. Crystallographic data: Cf(IO(3))(3), monoclinic, space group
      P2(1)/n, a = 8.7994(10) A, b = 5.9388(7) A, c = 15.157(2) A, beta = 96.833(2)
      degrees , V = 786.43(16) A(3), Z = 4 (T = 295 K).

PMID- 16411674
TI  - Phosphonium-borate zwitterions, anionic phosphines, and dianionic phosphonium
      dialkoxides via tetrahydrofuran ring-opening reactions.
AB  - Sterically demanding secondary phosphines and phosphides react with
      (THF)B(C(6)F(5))(3) (THF = tetrahydrofuran) to give the THF ring-opened compounds
      [R(2)PHC(4)H(8)OB(C(6)F(5))(3)] and [Mes(2)PC(4)H(8)OB(C(6)F(5))(3)Li(THF)(2)]
      (Mes = C(6)H(2)Me-2,4,6). These reactions also occur consecutively to give the
      double THF ring-opened compounds
      [Mes(2)P(C(4)H(8)OB(C(6)F(5))(3))(2)][Li(THF)(4)] and [t
      Bu(2)P(C(4)H(8)OB(C(6)F(5))(3))(2)Li].

PMID- 16411672
TI  - De novo design and spectroscopic characterization of a dinucleating copper
      binding pentadecapeptide.
AB  - A spectroscopic study of aqueous solutions of Ac-WGHGHGHGPGHGHGH-NH(2) (HGP)
      indicates that copper(II) binds to the peptide to form a 2:1 Cu(2+)/HGP complex
      with four nitrogen atoms in the copper coordination environment. Electron
      paramagnetic resonance (EPR) and UV-visible data suggest copper binding through
      the peptide backbone and imidazole nitrogen donors. Circular dichroism data show
      that HGP is unbound below pH 5.5 and is copper-saturated at pH 9 and above. The
      apo form of the peptide is unstructured in solution and is organized into a turn
      conformation in the presence of 2 mol equiv of Cu(2+) at basic pH. EPR
      measurements for 2:1 Cu(2+)/HGP solutions in the g = 2 region and within the pH
      range 7-11 exhibit axial spectra. A molecular-mechanics-minimized model of the
      Cu(2+)/HGP complex gave a Cu...Cu separation of 8 A.

PMID- 16411675
TI  - First 3D Pr(III)-Ni(II)-Na(I) polymer and a 3D Pr(III) open network based on
      pyridine-2,4,6-tricarboxylic acid.
AB  - The self-assembly of pyridine-2,4,6-tricarboxylic acid (H(3)ptc) with metal salts
      under hydrothermal conditions gave two novel coordination polymers, {[Pr(mu(5)
      ptc)(H(2)O)(2)].1.5H(2)O}(n)() (1) and {Na(2)NiPr(mu(4)-ClO(4))(mu(2)
      HOCH(2)CH(2)OH)(mu(4)-ptc)(2)(H(2)O)(8)}.4.5H(2)O}(n)() (2). 1 is a 3D open
      network with five ptc ligands coordinating with one metal center and carboxylate
      groups linking metal centers to form a (4,6) net. 2 is the first Pr/Ni/Na
      heterotrimetallic complex, a unique 3D framework containing four different
      bridged ligands in the system.

PMID- 16411676
TI  - Constitutional self-selection of [2 x 2] homonuclear grids from a dynamic mixture
      of copper(I) and silver(I) metal complexes.
AB  - This paper describes the controlled self-selection and quantitative parallel
      amplification of the homonuclear grid architectures derived from the same ligand
      1 of different conformational geometries and Cu+ and Ag+ metal ions of different
      coordination behavior and ionic size.

PMID- 16411677
TI  - Aryl isocyanate, carbodiimide, and isocyanide prepared from carbon dioxide. A
      metathetical group-transfer tale involving a titanium-imide zwitterion.
AB  - Carbon dioxide can be readily converted quantitatively and under mild conditions
      into the aryl isocyanate and symmetrical carbodiimide via a metathetical reaction
      involving a zwitterionic titanium imide (nacnac)Ti=NAr(CH(3)B(C(6)F(5))(3))
      (nacnac(-) = [ArNC((t)Bu)](2)CH, Ar = 2,6-(i)Pr(2)C(6)H(3)). The metathetical
      process to generate isocyanates allows also for facile formation of sterically
      demanding aryl isocyanide, by a deoxygenation route. Labeling studies using
      enriched (13)CO(2) are also described.

PMID- 16411678
TI  - Recognition of secondary structures in proteins by a diiron(III) complex via a
      hydrolytic pathway.
AB  - The diiron(III) complex Fe(2)(DTPB)(mu(2)-O)(mu(2)-OAc)Cl(BF(4))(2) [DTPB =
      1,1,4,7,7-pentakis(2'-benzimidazol-2-yl-methyl)triazaheptane, OAc = acetate]
      exhibits a similar affinity for proteins belonging to different structural
      patterns. However, this diiron complex is sensitive to secondary structures in a
      protein when it is used to promote the protein hydrolysis, indicating that some
      metal complexes, such as artificial proteolytic agents, could become a new
      hydrolytic probe of protein structures.

PMID- 16411679
TI  - High-resolution EXAFS of the active site of human sulfite oxidase: comparison
      with density functional theory and X-ray crystallographic results.
AB  - Much of our knowledge about molybdenum enzymes has originated from EXAFS
      spectroscopy. This technique provides excellent bond-length accuracy but has only
      limited bond-length resolution. We have used EXAFS spectroscopy with an extended
      data range in an attempt to improve bond-length resolution for the molybdenum
      enzyme sulfite oxidase. The Mo site of sulfite oxidase has two oxygen and three
      Mo-S ligands (two from cofactor dithiolene plus a cysteine). For the oxidized
      (Mo(VI)) enzyme, we find that the three Mo-S bond lengths are very similar
      (within 0.05 A) at 2.41 A, as are the Mo=O ligands at 1.72 A. Density functional
      theory shows that this is consistent with the proposed active-site structure. The
      reduced (Mo(IV)) enzyme shows two Mo-S bond lengths at 2.35 A and one at 2.41 A
      (assigned to cofactor dithiolene and cysteine, respectively, from DFT), together
      with one Mo=O at 1.72 A and one Mo-OH(2) at 2.30 A.

PMID- 16411680
TI  - Copper complexes of thiosemicarbazone-pyridylhydrazine (THYNIC) hybrid ligands: a
      new versatile potential bifunctional chelator for copper radiopharmaceuticals.
AB  - Two new thiosemicarbazone-pyridylhydrazine (THYNIC) hybrid ligands have been
      synthesized. Copper(II) and copper(I) complexes of the ligands have been prepared
      and characterized by X-ray crystallography. Cyclic voltammetry measurements show
      that the copper(II) complexes undergo quasi-reversible reductions at biologically
      accessible potentials. One of the ligands, bearing a pendant carboxylate arm, has
      been conjugated to N-alpha-(tert-butoxycarbonyl)-L-lysine.

PMID- 16411681
TI  - The central role of metal coordination in selenium antioxidant activity.
AB  - Oxidative DNA damage occurs in vivo by hydroxyl radical generated in metal
      mediated Fenton-type reactions. Cell death and mutation caused by this DNA damage
      are implicated in neurodegenerative and cardiovascular diseases, cancer, and
      aging. Treating these conditions with antioxidants, including highly potent
      selenium antioxidants, is of growing interest. Gel electrophoresis was used to
      directly quantify DNA damage inhibition by selenium compounds with copper and
      H(2)O(2). Selenocystine inhibited all DNA damage at low micromolar
      concentrations, whereas selenomethionine showed similar inhibition at 40 times
      these concentrations, and 2-aminophenyl diselenide showed no effect. DNA damage
      inhibition by these selenium compounds does not correspond to their glutathione
      peroxidase activities, and UV-vis and gel electrophoresis results indicate that
      selenium-copper coordination is essential for DNA damage inhibition.
      Understanding this novel metal-coordination mechanism for selenium antioxidant
      activity will aid in the design of more potent antioxidants to treat and prevent
      diseases caused by oxidative stress.

PMID- 16411682
TI  - Novel phosphoranido complex of rhodium(III) tetraphenylporphyrin. Synthesis and
      characterization.
AB  - A novel phosphoranido complex of rhodium(III) porphyrin was prepared by the
      reaction of a lithium phosphoranide, generated from a P-H phosphorane bearing two
      8-oxy-1-naphthyl groups, with (TPP)RhCl (TPP = dianion of 5,10,15,20
      tetraphenylporphyrin). The crystal structure of the complex was determined by X
      ray structural analysis.

PMID- 16411683
TI  - Unique asymmetric (CuII4) double-stranded helicate from a hexadentate piperazine
      based ligand: ligand conformation isomerism upon coordination.
AB  - In methanol, the reaction of Cu(ClO(4))(2).6H(2)O and a sterically constrained
      piperazine imine phenol ligand (H(2)L), in the presence of NEt(3), affords a
      novel tetranuclear copper(II) complex of formula [Cu(II)(4)(mu(3)-L)(2)(mu
      OH)(2)(H(2)O)(2)](ClO(4))(2).H(2)O (1). The X-ray structure of this complex shows
      an elongated Cu(4) quasi-tetrahedron coordinated to two hexadentate chair-(e,a)
      mu(3)-piperazine bridging ligands. Variable-temperature magnetic studies show an
      S(t) = 0 spin ground state resulting from antiferromagnetic interactions between
      Cu(II) ions within the complex.

PMID- 16411684
TI  - Facile light-triggered one-step synthesis of small and stable platinum
      nanoparticles in an aqueous medium from a beta-cyclodextrin host-guest inclusion
      complex.
AB  - It is shown, for the first time, that small (ca. 2 nm) and stable platinum
      nanoparticles can be easily obtained in one step through visible light
      irradiation of a host-guest inclusion complex between beta-cyclodextrin and
      platinum acetylacetonate in a water solution. The exclusive control of the
      reaction by an external trigger, the removal of the undesired reaction products
      without any manipulation of the sample, and the absence of ionic repulsions
      between the metal nanoparticles represent the main remarkable advantages offered
      by this synthetic methodology.

PMID- 16411685
TI  - Combining hard and soft donors in early-transition-metal olefin polymerization
      catalysts.
AB  - Bis(phosphanylphenoxide) complexes of the group 4 metals, upon activation by
      methylaluminoxane, are highly active for ethylene and propylene polymerization; a
      zirconium derivative possesses one of the highest propylene polymerization
      activities found to date for a nonmetallocene system.

PMID- 16411686
TI  - Structure of Mg2.56V1.12W0.88O8 and vibrational raman spectra of Mg2.5VWO8 and
      Mg2.5VMoO8.
AB  - Mg(2.56)V(1.12)W(0.88)O(8) crystals were grown from a MgO/V(2)O(5)/WO(3) melt. X
      ray single-crystal diffraction studies revealed that it is orthorhombic with
      space group Pnma, a = 5.0658(5) A, b = 10.333(1) A, c = 17.421(2) A, Z = 6, and
      is isostructural with Mg(2.5)VMoO(8). Raman spectra are reported, and the
      assignment of the Raman bands is made by comparing the metal-oxygen vibrations of
      VO(4)/WO(4) tetrahedra in Mg(2.5)VWO(8) with the metal-oxygen vibrations of
      VO(4)/MoO(4) tetrahedra in Mg(2.5)VMoO(8). The stretching vibrations appearing at
      1016 and 1035 cm(-)(1) are assigned to Mo=O and W=O double bonds, respectively,
      associated with the Mg(2+) cation vacancies.

PMID- 16411687
TI  - Probing the vanadyl and molybdenyl bonds in complex vanadomolybdate structures.
AB  - A solid solution was found to exist in the quaternary Li(2)O-MgO-V(2)O(5)-MoO(3)
      system between the two phases Mg(2.5)VMoO(8) and Li(2)Mg(2)(MoO(4))(3). Both
      Mg(2.5)VMoO(8) and Li(2)Mg(2)(MoO(4))(3) are isostructural with the mineral
      lyonsite, and substitution according to the formula square(1/4
      x/6)Li(4x/3)Mg(15/4-7x/6)V(3/2-x)Mo(3/2+x)O(12) (0 < or = x < or = 1.5, where
      square denotes a cation vacancy) demonstrates that a complete solid solution
      exits coupling the addition of molybdenum and lithium with the subtraction of
      cation vacancies, magnesium, and vanadium and vice versa. Vibrational Raman
      spectroscopy indicates that molybdenum-oxo double bonds preferentially associate
      with the cation vacancies.

PMID- 16411688
TI  - Fast magnetization tunneling in tetranickel(II) single-molecule magnets.
AB  - A series of Ni(4) cubane complexes with the composition [Ni(hmp)(ROH)Cl](4)
      complexes 1-4 where R= -CH(3) (complex 1), -CH(2)CH(3) (complex 2), 
      CH(2)CH(2)(C(4)H(9)) (complex 3), -CH(2)CH(2)CH(2)(C(6)H(11)) (complex 4), hmp(-)
      is the anion of 2-hydroxymethylpyridine, t-Buhmp(-) is the anion of 4-tert-butyl
      2-hydroxymethylpyridine, and dmb is 3,3-dimethyl-1-butanol] and
      [Ni(hmp)(dmb)Br](4) (complex 5) and [Ni(t-Buhmp)(dmb)Cl](4) (complex 6) were
      prepared. All six complexes were characterized by dc magnetic susceptibility data
      to be ferromagnetically coupled to give an S = 4 ground state with significant
      magnetoanisotropy (D approximately equal to -0.6 cm(-1)). Magnetization
      hysteresis measurements carried out on single crystals of complexes 1-6 establish
      the single-molecule magnet (SMM) behavior of these complexes. The exchange bias
      observed in the magnetization hysteresis loops of complexes 1 and 2 is
      dramatically decreased to zero in complex 3, where the bulky dmb ligand is
      employed. Fast tunneling of magnetization is observed for the high-symmetry (S(4)
      site symmetry) Ni(4) complexes in the crystal of complex 3, and the tunneling
      rate can even be enhanced by destroying the S(4) site symmetry, as is the case
      for complex 4, where there are two crystallographically different Ni(4)
      molecules, one with C(2) and the other with C(1) site symmetry. Magnetic ordering
      temperatures due to intermolecular dipolar and magnetic exchange interactions
      were determined by means of very low-temperature ac susceptibility measurements;
      complex 1 orders at 1100 mK, complex 3 at 290 mK, complex 4 at approximately 80
      mK, and complex 6 at <50 mK. This confirms that bulkier ligands correspond to
      more isolated molecules, and therefore, magnetic ordering occurs at lower
      temperatures for those complexes with the bulkiest ligands.

PMID- 16411689
TI  - Tuning the electronic communication and rates of intramolecular electron transfer
      of dimers of trinuclear ruthenium clusters: bridging and ancillary ligand
      effects.
AB  - Ten new bridged dimers of oxo-centered triruthenium clusters with CO and 4
      (dimethylamino)pyridine (dmap), pyridine (py), or 4-cyanopyridine (cpy) as
      terminal ligands and pyrazine-d(4) (d(4)-pz), 2,5-dimethylpyrazine (dmpz), 2
      methylpyrazine (mpz), and 2-chloropyrazine (clpz) as bridging ligands were
      prepared. The carbonyl stretching frequency, nu(CO), was used as a probe for
      infrared spectroelectrochemical measurements. In the neutral and doubly reduced
      states, a single band was observed for each of the dimers, with a shift in
      frequency due to the oxidation state of the triruthenium clusters. In the singly
      reduced state, a range of nu(CO) line shapes was observed, depending on the
      nature of the ligands, from two bands centered at the frequencies of the bands of
      the neutral and doubly reduced species to one broad band at the average of these
      two frequencies. By synthesizing new combinations of bridging and ancillary
      ligands, electronic communication between two bridged triruthenium clusters was
      effectively tuned, and electron-transfer rates were estimated by IR spectral line
      shape analysis. In dimers bridged by the asymmetric ligand mpz, it was possible
      through selective isotope labeling of one CO ligand to observe "mixed-valence
      isomers," the two alternate charge distributions of a mixed-valence complex.

PMID- 16411690
TI  - 6-methylpyridyl for pyridyl substitution tunes the properties of fluorescent zinc
      sensors of the Zinpyr family.
AB  - To prepare fluorescent zinc sensors with binding affinities lower than that of
      the parent 9-(o-carboxyphenyl)-2,7-dichloro-4,5-bis(bis(2
      pyridylmethyl)methylaminomethyl)-6-hydroxy-3-xanthenone (ZP1), dimethylated and
      tetramethylated derivatives were synthesized having either two or four of the
      pyridyl subunits methylated at the 6-position. Like the parent ZP1, both Me(2)ZP1
      and Me(4)ZP1 exhibit increased fluorescence in the presence of Zn(2+). The
      integrated emission of Me(2)ZP1 increases 4-fold in the presence of excess zinc,
      whereas Me(4)ZP1 displays 2.5-fold enhanced fluorescence for Zn(2+). Methylating
      the 6-positions of the pyridyl rings raises the dissociation constant of the
      sensors and lowers the pK(a) values associated with the tertiary amine ligands in
      a systematic manner. The properties of the dimethylated Me(2)ZP1 dye resemble
      those of ZP1, but the tetramethylated Me(4)ZP1 differs greatly from ZP1 in terms
      of its brightness, affinity toward Zn(2+), exchange kinetics, and metal
      sensitivity. Both Me(2)ZP1 and Me(4)ZP1 can enter HeLa cells and signal the
      presence of Zn(2+). Staining caused by both dyes is punctate, with localization
      patterns resembling that observed for ZP1.

PMID- 16411691
TI  - Mononuclear to polynuclear transition induced by ligand coordination: synthesis,
      X-ray structure, and properties of mono-, di-, and polynuclear copper(II)
      complexes of pyridyl-containing azo ligands.
AB  - Reactions of two hydrated cupric salts (CuCl(2).2H(2)O and Cu(ClO(4))(2).6H(2)O)
      with three azopyridyl ligands, viz. 2-[(arylamino)phenylazo]pyridine [aryl =
      phenyl (HL(1a)), p-tolyl (HL(1b)), and 2-thiomethyl phenyl (HL(1c))], 2-[2
      (pyridylamino)phenylazo]pyridine (HL(2)), and 2-[3
      (pyridylamino)phenylazo]pyridine (HL(3)), afford the mononuclear [CuClL(1)] (1),
      dinuclear [Cu(2)X(2)L(2)(2)](n)()(+) (X = Cl, H(2)O, ClO(4); n = 0, 1; 2, 3), and
      polynuclear [CuClL(3)](n)() (4) complexes, respectively, in high yields.
      Representative X-ray structures of these complexes 1-4 are reported. X-ray
      structure analysis of 4 reveals an infinite 1D zigzag chain that adopts a saw
      tooth-like structure. Variable-temperature cryomagnetic measurements (2-300 K) on
      the complexes 2-4 have revealed weak magnetic interactions between the copper
      centers with J values -1.04, 9.88, and -1.31 cm(-1), respectively. Positive ion
      ESI mass spectra of the soluble complexes 1-3 are studied which provide the
      evidence for the integrity of the complexes also in solution. Visible range
      spectra of the complexes 1-3 in solution consist of intense and broad transitions
      in the range 700-600 nm. The solid-state spectrum of the insoluble copper complex
      4, on the other hand, shows a structured band near 700 nm. The intensities of the
      transitions of the dinuclear complexes are much higher than those of the
      corresponding mononuclear copper complexes. Redox properties of the present
      copper complexes are reported. Notably, the dinuclear complex, 3, displays two
      successive redox processes: Cu(II)Cu(II) right harpoon over left harpoon
      Cu(II)Cu(I) right harpoon over left harpoon Cu(I)Cu(I). It catalyzes aerial
      oxidation of L-ascorbic acid. The catalytic cycle is most effective up to H(2)A/3
      (H(2)A = L-ascorbic acid) molar ratio of 20:1.

PMID- 16411692
TI  - Investigation of group 12 metal complexes with a tridentate SNS ligand by X-ray
      crystallography and 1H NMR spectroscopy.
AB  - Two series of zinc triad complexes containing the ligand 2,6
      bis(methylthiomethyl)pyridine (L1) were synthesized and characterized by X-ray
      crystallography and solution-state 1H NMR spectroscopy. The distorted meridional
      octahedral M(L1)2(ClO4)2 series includes the first structurally characterized
      Zn(II) and Cd(II) complexes with N2(SR2)4 coordination spheres. Coordination of
      HgCl2 and ZnCl2 with 1 equiv of ligand afforded mononuclear, five-coordinate
      species Hg(L1)Cl2 and Zn(L1)Cl2, respectively, with distorted square-pyramidal
      and trigonal-bipyramidal geometries. With CdCl2, the dimeric [Cd(L1)Cl(mu-Cl)]2
      complex was obtained. The distorted octahedral coordination geometry of each
      Cd(II) center in this complex is formed by one tridentate ligand, two bridging
      chloride ions, and one terminal chloride ion. NMR spectra indicate that the
      intermolecular ligand-exchange rate of [M(L1)2](2+) decreased in the order Cd(II)
      > Zn(II) > Hg(II). Slow intermolecular ligand-exchange conditions on the chemical
      shift time scale were found for 1:2 metal-to-ligand complexes of L(1) with Hg(II)
      and Zn(II) but not Cd(II). Slow intermolecular ligand-exchange conditions in
      acetonitrile-d(3) solutions permitting detection of (3-5)J(199Hg1H) were found
      for 1:1 and 1:2 Hg(ClO4)2/L1 complexes, but not for the related Cd(ClO4)2)
      complexes. The magnitudes of J(199Hg1H) for equivalent protons were smaller in
      [Hg(L1)2](2+) than in [Hg(L1)(NCCH3)x](2+). The relative intermolecular ligand
      exchange rates of the zinc triad complexes investigated here suggest that the
      toxicity of Hg(II) is accentuated by the relative difficulty of displacing it
      from the coordination sites encountered.

PMID- 16411693
TI  - Syntheses, structures, and magnetic properties of cyano-bridged heterobimetallic
      complexes based on [Fe(bpca)(CN)3]-.
AB  - Two new cyano-bridged one-dimensional heterobimetallic coordination polymers,
      [(bpca)(2)Fe(III)(2)(CN)(6)Cu(H(2)O)(2).1.5H(2)O](n)() (2) and
      [(bpca)Fe(III)(CN)(3)Cu(bpca)(H(2)O).H(2)O](n)() (3), and a trinuclear complex,
      [(bpca)(2)Fe(III)(2)(CN)(6)Mn(CH(3)OH)(2)(H(2)O)(2)].2H(2)O (4), have been
      synthesized using the tailored tricyanometalate precursor
      (Bu(4)N)[Fe(bpca)(CN)(3)].H(2)O (1) (Bu(4)N(+) = tetrabutylammonium cation; bpca
      = bis(2-pyridylcarbonyl)amidate anion) as a building block and structurally
      characterized. In complex 2, the Cu(II) ions are six-coordinated in an elongated
      distorted octahedral environment, and they are linked by distorted octahedrons of
      [Fe(bpca)(CN)(3)](-) to form 1D chain of squares. Complex 3 is an unexpected
      chiral heterobimetallic helical chain complex, in which the helical chain
      consists of the asymmetric unit of [(bpca)Fe(CN)(3)Cu(bpca)(H(2)O)]. In complex
      4, there are two independent trinuclear clusters in one asymmetric unit, and the
      coordination modes of the two methanol and two water molecules coordinating to
      the central Mn(II) ion are different (cis and trans). Complex 2 shows
      metamagnetic behavior with a Neel temperature of T(N) = 2.2 K and a critical
      field of 250 Oe at 1.8 K, where the cyanides mediate the intrachain ferromagnetic
      coupling between the Cu(II) and Fe(III) ions. Complex 3 shows ferromagnetic
      coupling between Cu(II) and Fe(III) ions, the best-fit for chi(M)T versus T using
      a 1D alternating chain model leads to the parameters J(1) = 7.9(3) cm(-)(1), J(2)
      = 1.03(2) cm(-)(1), and g = 2.196(3). Complex 4 exhibits ferrimagnetic behavior
      caused by the noncompensation of the local interacting spins (S(Mn) = 5/2 and
      S(Fe) = 1/2) which interact antiferromagnetically through bridging cyano groups.

PMID- 16411694
TI  - Supramolecular assembly of gold(I) complexes of diphosphines and N,N'-bis-4
      methylpyridyl oxalamide.
AB  - We report herein the supramolecular assembly and spectroscopic and luminescent
      properties of gold(I) complexes of diphosphines (dppm
      [bis(diphenylphosphino)methane], dppp [1,3-bis(diphenylphosphino)propane], and
      dpppn [1,5-bis(diphenylphosphino)pentane]) and N,N'-bis-4-methylpyridyl oxalamide
      (L). The dppm and dppp cases form the rectangular structures,
      [dppm(Au(2))L](2)(ClO(4))(4) and [dppp(Au(2))L](2)(ClO(4))(4), with four gold(I)
      ions at the corners, as well as two L and two dppm or dppp ligands as edges,
      featuring 38- and 42-membered rings for the former and the latter, respectively.
      Remarkably, the packing of the dppp complexes shows interesting one-dimensional
      rectangular channels in the solid state, most likely due to intermolecular
      pi...pi interactions. The dpppn complex has been structurally characterized as a
      one-dimensional coordination polymer, {[(dpppn)(3.5)(Au(7))L(3.5)](PF(6))(7)}.
      The absorptions and emissions of the compounds are in general due to intraligand
      transitions, but aurophilic or pi...pi interactions could also make partial
      contributions. The dipyridyl amide system with the amides incorporated into the
      bridging ligands as well as the one-dimensional rectangular channels in the solid
      state for the dppp-based rectangle make this a promising family of metal
      containing cyclic peptides in crystal engineering and molecular-recognition
      studies.

PMID- 16411695
TI  - Syntheses, structures, and magnetic properties of inorganic-organic hybrid
      cobalt(II) phosphites containing bifunctional ligands.
AB  - Seven new cobalt(II) phosphites, [Co(HPO(3))(C(14)H(14)N(4))(H(2)O)(2)].2H(2)O
      (1), [Co(HPO(3))(C(22)H(18)N(4))].H(2)O (2),
      [Co(2)(HPO(3))(2)(C(22)H(18)N(4))(2)H(2)O].H(2)O (3),
      [Co(2)(HPO(3))(2)(C(12)H(10)N(4))(1.5)H(2)O].1.5H(2)O (4),
      [Co(HPO(3))(C(14)H(14)N(4))(0.5)].H(2)O (5), [Co(HPO(3))(C(18)H(16)N(4))(0.5)]
      (6), and [Co(HPO(3))(C(18)H(16)N(4))(0.5)] (7) were synthesized in the presence
      of 1,2-bis(imidazol-1-ylmethyl)benzene (L1), 1,4-bis(benzimidazol-1
      ylmethyl)benzene (L2), 1,3-bis(benzimidazol-1-ylmethyl)benzene (L3), 1,4-bis(1
      imidazolyl)benzene (L4), 1,4-bis(imidazol-1-ylmethyl)benzene (L5), 1,4
      bis(imidazol-1-ylmethyl)naphthalene (L6), and 1,5-bis(imidazol-1
      ylmethyl)naphthalene (L7), respectively, and their structures were determined by
      X-ray crystallography. Compound 1 is a molecular compound in which two cobalt(II)
      ions are held together by double mu-O linkages. The inorganic framework of
      compounds 2 and 3 are composed of vertex-shared CoO(2)N(2)/CoO(3)N(2) and HPO(3)
      polyhedra that form four rings; these are further linked by an organic ligand to
      generate 2D sheets. Compounds 4 and 5 both have 1D inorganic structures, with the
      bifunctional ligands connected to each side of the ladder by coordination bonds
      to give 2D hybrid sheets. A 3D organically pillared hybrid framework is observed
      in 6 and 7. In 6, the stacking of the interlayer pillars gives rise to a small
      hydrophobic channel that extends through the entire structure parallel to the
      sheets. The temperature-dependent magnetic susceptibility measurements of these
      compounds show weak interactions between the metal centers, mediated through the
      mu-O and/or O-P-O linkages.

PMID- 16411696
TI  - Aggregation of [(tBu3SiS)MX]: structures of {[Br2Fe(mu
      SSitBu3)2)FeBr(THF)]Na(THF)4}infinity, cis-[(THF)FeI]2(mu-SSitBu3)2,
      [(tBu3SiS)Fe]2(mu-SSitBu3)2, and comparative structure and magnetism studies of
      [(tBu3SiS)MX]n (M = Fe, Co, X = Cl, n = 12; M = Fe, Ni, X = Br, n = 12; M = Fe, X
      = I, n = 14).
AB  - A convenient synthesis of (t)Bu(3)SiSH and (t)Bu(3)SiSNa(THF)(x)() led to the
      exploration of "(t)Bu(3)SiSMX" aggregation. The dimer, [((t)Bu(3)SiS)Fe](2)(mu
      SSi(t)Bu(3))(2) (1(2)), was formed from [{(Me(3)Si)(2)N}Fe](2)(mu
      N(SiMe(3))(2))(2) and the thiol, and its dissolution in THF generated
      ((t)Bu(3)SiS)(2)Fe(THF)(2) (1-(THF)(2)). Metathetical procedures with the
      thiolate yielded aggregate precursors [X(2)Fe](mu
      SSi(t)Bu(3))(2)[FeX(THF)]Na(THF)(4) (3-X, X = Cl, Br) and cis-[(THF)IFe](2)(mu
      SSi(t)Bu(3))(2) (4). Thermal desolvations of 3-Cl, 3-Br and 4 afforded molecular
      wheels [Fe(mu-X)(mu-SSi(t)Bu(3))](12)(C(6)H(6))(n) (5-FeX, X = Cl, Br) and the
      ellipse [Fe(mu-I)(mu-SSi(t)Bu(3))](14)(C(6)H(6))(n) (6-FeI). Related metathesis
      and desolvation sequences led to wheels [Co(mu-Cl)(mu
      SSi(t)Bu(3))](12)(C(6)H(6))(n) (5-CoCl) and [Ni(mu-Br)(mu
      SSi(t)Bu(3))](12)(C(6)H(6))(n) (5-NiBr). The nickel wheel disproportionated to
      give, in part, [((t)Bu(3)SiS)Ni](2)(mu-SSi(t)Bu(3))(2) (7), which was also
      synthesized via salt metathesis. X-ray structural studies of 1(2) revealed a
      roughly planar Fe(2)S(4) core, while 1-(THF)(2), 3-Br, and 4 possessed simple
      distorted tetrahedral and edge-shared tetrahedral structures. X-ray structural
      studies revealed 5-MX (MX = FeCl, FeBr, CoCl, NiBr) to be wheels based on edge
      shared tetrahedra, but while the pseudo-D(6)(d) wheels of 5-FeCl, 5-CoCl, and 5
      FeBr pack in a body-centered arrangement, those of pseudo-C(6)(v)() 5-NiBr
      exhibit hexagonal packing and two distinct trans-annular d(Br...Br). Variable
      temperature magnetic susceptibility measurements were conducted on 5-FeCl, 5
      CoCl, 5-FeBr, and 6-FeI, and the latter three are best construed as weakly
      antiferromagnetic, while 5-FeCl exhibited modest ferromagnetic coupling. Features
      suggesting molecular magnetism are most likely affiliated with phase changes at
      low temperatures.

PMID- 16411697
TI  - On the flexibility of the structural framework of cubic LAMOX compounds, in
      relationship with their anionic conduction properties.
AB  - A mathematical analysis of the cubic crystal structure of fast oxide-ion
      conductor beta-La(2)Mo(2)O(9) (and derived members of the LAMOX family) shows
      that its cationic sublattice can behave as a semirigid framework. Tilt/rotation
      of rigid [O1La(3)Mo] anti-tetrahedral units about their 3-fold axis can open up
      tunnels in the cationic framework, therefore favoring the mobility of O2 and O3
      oxide ions located in these tunnels, as confirmed by molecular dynamics
      simulations. Such a process is likely to assist the anionic transport and explain
      the postulated transition from Arrhenius-type to VTF (Vogel-Tamman-Fulcher)-type
      behavior propounded to account for the peculiar conductivity curvature observed
      at high temperature in all the cubic LAMOX compounds. It also clarifies the
      correlated extra cell volume expansion observed at the same temperature in all
      these materials.

PMID- 16411698
TI  - Syntheses and structures of dinuclear double-stranded helicates of divalent
      manganese, iron, cobalt, and zinc.
AB  - The syntheses and solid-state and solution structures of a series of unusually
      volatile, charge neutral, [4 + 4] double-stranded helical complexes of divalent
      manganese, iron, cobalt, and zinc are described. Deprotonation of the N4-donor
      iminopyrrole ligand H2L by KH cleanly generates the salt K2(THF)2L, which
      displays both sigma and pi interactions between K and iminopyrrolyl fragments in
      the X-ray crystal structure. Transamination, salt elimination, and protonolysis
      reactions were found to be versatile and, in general, high-yielding routes to the
      dinuclear double helicates [M2(L)2] (M = Mn, Fe, Co, and Zn). These compounds are
      isomorphous in the solid state by X-ray crystallography and adopt dinuclear cleft
      motifs as a result of pi stacking between opposing iminopyrrolyl fragments. This
      motif was also observed in the solution structures of [Fe2(L)2] and [Zn2(L)2]
      below 230 and 200 K, respectively (DeltaG++ = approximately 46 and 39.0 kJ mol(
      1), respectively).

PMID- 16411699
TI  - Novel example of a chain structure formed by 1,4-dioxane and cobalt(II) links.
      Chain [Co3(mu-OOCCF3)4(mu-H2O)2(OOCCF3)2(H2O)2(C4H8O2)].2C4H8O2.
AB  - The trimer [Co3(mu-OOCCF3)4(mu-H2O)2(OOCCF3)2(H2O)2(C4H8O2)].2C4H8O2. (1) is
      composed of three tetragonally distorted Co(II) centers bridged by four
      trifluoroacetates and two bridging water molecules. 1,4-Dioxane is coordinated at
      a distance of 2.120(3) A from the terminal cobalt Co2; the remaining oxygen of
      this 1,4-dioxane links the terminal cobalt to a neighbor trimer, forming a one
      dimensional chain. The crystal structure displays a network of hydrogen bonds
      between four noncoordinated 1,4-dioxane molecules and the coordinated terminal
      water molecules. The magnetic properties of 1 were analyzed with the use of the
      Hamiltonian including isotropic exchange interactions between real spins of a
      high-spin Co(II), spin-orbit coupling and a low-symmetry crystal field acting
      within the (4)T(1g) ground manifold of each cobalt ion. A weak antiferromagnetic
      exchange interaction between cobalt ions in 1 was found. The results of the
      magnetic model are in good agreement with the experimental observations.

PMID- 16411700
TI  - Homochiral and heterochiral coordination polymers and networks of silver(I).
AB  - The self-assembly of racemic and enantiopure binaphthylbis(amidopyridyl) ligands
      1,1'-C(20)H(12){NHC(O)-4-C(5)H(4)N}(2), 1, and 1,1'-C(20)H(12){NHC(O)-3
      C(5)H(4)N}(2), 2, with silver(I) salts (AgX; X = CF(3)CO(2), CF(3)SO(3), NO(3))
      to form extended metal-containing arrays is described. It is shown that the self
      assembly with racemic ligands can lead to homochiral or heterochiral polymers,
      through self-recognition or self-discrimination of the ligand units. The primary
      polymeric materials adopt helical conformations (secondary structure), and they
      undergo further self-assembly to form sheets or networks (tertiary structure).
      These secondary and tertiary structures are controlled through secondary bonding
      interactions between pairs of silver(I) centers, between silver cations and
      counteranions, or through hydrogen bonding involving amide NH groups. The self
      assembly of the enantiopure ligand R-1 with silver trifluoroacetate gave a
      remarkable three-dimensional chiral, knitted network composed of polymer chains
      in four different supramolecular isomeric forms.

PMID- 16411701
TI  - (Strept)avidin as host for biotinylated coordination complexes: stability, chiral
      discrimination, and cooperativity.
AB  - Incorporation of a biotinylated ruthenium tris(bipyridine) [Ru(bpy)(2)(Biot
      bpy)](2+) (1) in either avidin or streptavidin-(strept)avidin-can be conveniently
      followed by circular dichroism spectroscopy. To determine the stepwise
      association constants, cooperativity, and chiral discrimination properties,
      diastereopure (Lambda and Delta)-1 species were synthesized and incorporated in
      tetrameric (strept)avidin to afford (Delta-[Ru(bpy)(2)(Biot-bpy)](2+))(x)()
      subsetavidin, (Lambda-[Ru(bpy)(2)(Biot-bpy)](2+))(x)() subsetavidin, (Delta
      [Ru(bpy)(2)(Biot-bpy)](2+))(x)() subsetstreptavidin, and (Lambda-[Ru(bpy)(2)(Biot
      bpy)](2+))(x)() subsetstreptavidin (x = 1-4) For these four systems, the overall
      stability constants are log beta(4) = 28.6, 30.3, 36.2, and 36.4, respectively.
      Critical analysis of the CD titrations data suggests a strong cooperativity
      between the first and the second binding event (x = 1, 2) and a pronounced
      difference in affinity between avidin and streptavidin for the dicationic guest 1
      as well as modest enantiodiscrimination properties with avidin as host.

PMID- 16411702
TI  - Reactions of (CF3)3BCO with amines and phosphines.
AB  - Reactions of tris(trifluoromethyl)borane carbonyl, (CF(3))(3)BCO, with ammonia
      yielded either a mixture of [NH(4)][(CF(3))(3)BC(O)NH(2)],
      [NH(4)][(CF(3))(3)BCN], and [NH(4)](2)[{(CF(3))(3)BC(O)}(2)NH] or neat
      [NH(4)](2)[{(CF(3))(3)BC(O)}(2)NH] depending on the reaction conditions. The salt
      K[(CF(3))(3)BC(O)NH(2)] was obtained as the sole product from the reaction of
      NH(3) with K[(CF(3))(3)BC(O)F]. A simple synthesis for
      cyanotris(trifluoromethyl)borates, M[(CF(3))(3)BCN], was developed by dehydration
      of M[(CF(3))(3)BC(O)NH(2)] (M = [NH(4)], K) using phosgene. In addition,
      syntheses of the tris(trifluoromethyl)boron species [(CF(3))(3)BC(O)NH(n)()Pr](
      ), [(CF(3))(3)BC(O)NMe(2)](-), and (CF(3))(3)BC(O)NMe(3), as well as of
      (CF(3))(3)BC(O)PMe(3), were performed. All species were characterized by
      multinuclear NMR spectroscopy. As far as neat substances resulted, IR and Raman
      spectra were recorded and their thermal behaviors were studied by differential
      scanning calorimetry. The interpretation of reaction pathways, structures, and
      vibrational spectra are supported by DFT calculations. The solid-state structure
      of K(2)[{(CF(3))(3)BC(O)}(2)NH].2MeCN was determined by single-crystal X-ray
      diffraction.

PMID- 16411703
TI  - MS2(Me2PC2H4PMe2)2 (M = Mo, W): acid-base properties, proton transfer, and
      reversible protonolysis of sulfido ligands.
AB  - The acid-base reactivity of MS(2)(dmpe)(2), where M = Mo (1) and W (2) and dmpe =
      Me(2)PCH(2)CH(2)PMe(2), was examined. Compounds 1 and 2 arise via the one-pot
      reaction of (NH(4))(2)MS(4) and dmpe. Protonation of these species gives the
      stable salts [MS(SH)(dmpe)(2)]X. The pK(a)'s of the Mo and W compounds are
      estimated to be 16.5 and 15.5, respectively. Protonation causes the M=S distances
      to diverge from 2.24 A to 2.06 and 2.57 A, whereas the Mo-P distances do not
      change appreciably. (1)H and (31)P NMR studies for [1H]BAr(F)(4) reveal that the
      proton exchange is competitive with the NMR time scale; at low temperatures,
      individual signals for both the parent disulfide and its conjugate acid can be
      observed. Treatment of 1 with excess HOTf liberates H(2)S to afford
      [MoS(OTf)(dmpe)(2)]OTf, which forms an adduct with CD(3)CN and regenerates 1 upon
      treatment with SH(-)/Et(3)N solutions. Consistent with its ready protonation,
      complex 1 is methylated, and the use of excess MeOTf gives [MoS(OTf)(dmpe)(2)](+)
      and Me(2)S in a rare example of double alkylation at a sulfido ligand.

PMID- 16411704
TI  - Orbital angular momentum contribution to the magneto-optical behavior of a
      binuclear cobalt(II) complex.
AB  - We report magnetic and magnetic circular dichroism investigations of a binuclear
      Co(II) compound. The Hamiltonian of the system involves an isotropic exchange
      interaction dealing with the real spins of cobalt(II) ions, spin-orbit coupling,
      and a low-symmetry crystal field acting within the (4)T(1g) ground manifold of
      each cobalt ion. It is shown that spin-orbit coupling between this ground term
      and the low-lying excited ones can be taken into consideration as an effective g
      factor in the Zeeman part of the Hamiltonian. The value of this g factor is
      estimated for the averaged experimental values of Racah and cubic ligand field
      parameters for high-spin cobalt(II). The treatment of the Hamiltonian is
      performed with the use of a irreducible tensor operator technique. The results of
      the calculation are in good agreement with experimental observations. Both a
      large effective g factor for the ground state and a large temperature-independent
      part of the magnetic susceptibility arise because of a strong orbital
      contribution to the magnetic behavior of the Co(II) dimer.

PMID- 16411705
TI  - A new family of ruthenium(II) polypyridine complexes bearing 5-aryltetrazolate
      ligands as systems for electrochemiluminescent devices.
AB  - A new family of mono- and dinuclear ruthenium polypyridyl complexes containing 5
      aryltetrazolate ligands such as the deprotonated form of 4-(1H-tetrazol-5
      yl)benzonitrile (4-TBNH) and bis(1H-tetrazol-5-yl)benzene (BTBH(2)) have been
      synthesized and thoroughly characterized. The reactivity of the mononuclear
      species toward different electrophiles such as H(+) and CH(3)(+) has been
      investigated, and the effects of the resulting regioselective electrophilic
      attacks on the electronic and structural properties of the tetrazolate ligand
      have been studied by NMR ((1)H, (13)C) spectroscopy and X-ray crystal structures.
      Absorption and emission spectroscopy, together with an electrochemical and UV-vis
      NIR spectroelectrochemical investigation of the uncoordinated ligand and
      complexes, has been performed, highlighting a rather good luminescence efficiency
      and a poor bridge-mediated electronic communication between the metal centers of
      the dinuclear complexes. The electrogenerated chemiluminescence (ECL) of the
      dinuclear species has been explored, and for one of these, an exceptionally high
      ECL efficiency has been observed, comparable to that of [Ru(bpy)(3)](2+), which
      is considered a standard in ECL studies.

PMID- 16411707
TI  - [Cd2(Te6O13)][Cd2Cl6] and Cd7Cl8(Te7O17): novel tellurium(IV) oxide slabs and
      unusual cadmium chloride architectures.
AB  - Initial attempts to prepare new Ln-Cd-Te-O-Cl compounds led to the isolation of
      two novel cadmium tellurium(IV) oxychlorides with two different types of
      structures, namely, [Cd(2)(Te(6)O(13))][Cd(2)Cl(6)] and Cd(7)Cl(8)(Te(7)O(17)).
      Both compounds feature novel polymeric tellurium(IV) oxide anions and unusual
      cadmium chloride substructures. The structure of [Cd(2)(Te(6)O(13))][Cd(2)Cl(6)]
      is composed of 1D [Cd(2)Cl(6)](2)(-) double chains and (002)
      [Cd(2)(Te(6)O(13))](2+) layers. The 1D Te(6)O(13)(2)(-) slab of the
      [Cd(2)(Te(6)O(13))](2+) layer is formed by TeO(3), TeO(4), and TeO(5) groups via
      corner- and edge-sharing, and it contains six- and seven-membered tellurium(IV)
      polyhedral rings. The structure of Cd(7)Cl(8)(Te(7)O(17)) features a 3D network
      with long-narrow tunnels along the b axis. The two types of structural building
      blocks are 1D [Te(7)O(17)](6)(-) anions and unusual corrugated [Cd(7)Cl(8)](6+)
      layers based on "cyclohexane-like" Cd(3)Cl(3) rings.

PMID- 16411706
TI  - E2(CN)2 (E = S, Se) and related compounds.
AB  - A synthetic, spectroscopic, and theoretical study of Ex(CN)2 (E = S, Se; x = 1-3)
      is described. The X-ray structures of Se2(CN)2 and Se3(CN)2 have been determined.
      Se2(CN)2 crystallizes in a chiral space group with the CN groups approximately
      gauche.

PMID- 16411708
TI  - Large gas-solid structural differences in complexes of haloacetonitriles with
      boron trifluoride.
AB  - The structural properties of the singly halogenated derivatives of CH(3)CN-BF(3)
      (X-CH(2)CN-BF(3): X = F, Cl, Br, I) have been investigated via single-crystal X
      ray crystallography, solid-state infrared spectroscopy, and correlated electronic
      structure theory. Taken together, these data illustrate large differences between
      the gas-phase and solid-state structures of these systems. Calculated gas-phase
      structures (B3PW91/aug-cc-pVTZ) of FCH(2)CN-BF(3), ClCH(2)CN-BF(3), and BrCH(2)CN
      BF(3) indicate that the B-N dative bonds in these systems are quite weak, with
      distances of 2.422, 2.374, and 2.341 A, respectively. However, these distances,
      as well as other calculated structural parameters and normal-mode vibrational
      frequencies, indicate that the dative interactions do become slightly stronger in
      proceeding from F- to Br-CH(2)CN-BF(3). In contrast, solid-state structures for
      FCH(2)CN-BF(3), ClCH(2)CN-BF(3), and ICH(2)CN-BF(3) from X-ray crystallography
      all have B-N distances that are quite short, about 1.65 A. Thus, the B-N
      distances of the F- and Cl-containing derivatives contract by over 0.7 A upon
      crystallization. Large shifts in the vibrational modes involving motions of the
      BF(3) subunit parallel these structural changes. An X-ray crystal structure could
      not be determined for BrCH(2)CN-BF(3)(s), but the solid-state IR spectrum is
      consistent with those obtained previously for related complexes and suggests that
      the solid-state structure resembles those of the others, and in turn, implicates
      a large gas-solid structural difference for this species as well.

PMID- 16411709
TI  - Stable 8-hydroxyquinolinate-based podates as efficient sensitizers of lanthanide
      near-infrared luminescence.
AB  - New polydentate ligands (e.g., Tsox and TsoxMe) have been synthesized to take
      advantage of the chelating effect of bidentate 8-hydroxyquinolinate subunits
      connected to a N,N,N',N'-tetraaminopropyl-1,2-ethylenediamine framework and with
      the aim of sensitizing the NIR luminescence of Nd(III) and Yb(III) ions. Ten
      pK(a)'s have been determined and the interaction between the ligands and Ln(III)
      ions in dilute aqueous solution has been probed both by potentiometric and
      spectrophotometric titrations. These studies have been mostly performed with the
      Eu(III) ion, which is in the middle of the lanthanide series, and extended to
      other ions (La(III), Er(III), Lu(IIII)). Stable complexes with Ln(III) ions are
      formed (pLn in the range of 14-16), the four chromophoric units being coordinated
      to the metal center, exploiting the entropic effect generated by the anchor. The
      monometallic complexes [Ln(H(2)L)](3)(-) exist as the major species at
      physiological pH regardless of the lanthanide used. Lifetime determinations of
      the Nd((4)F(3/2)) and Yb((2)F(5/2)) excited levels in both H(2)O and D(2)O at
      buffered pH point to the absence of water molecules bound in the inner
      coordination sphere of the Ln(III). Photophysical properties of the free ligands
      and of their lanthanide complexes have been investigated in buffered aqueous
      solutions both at room temperature and 77 K. The low-energy triplet state makes
      energy transfers from the ligand to the metal ions possible; this leads to a
      sizable sensitization of the Nd(III)- or Yb(III)-centered luminescence ( = 0.02%
      and = 0.18%) for Tsox chelates. Methylation of the amide functions removes the
      quenching mechanism induced by the proximate N-H vibrations and increases both
      the lifetimes and quantum yields of the TsoxMe chelates ( = 0.04% and = 0.37%).
      In fact, TsoxMe yields one of the most luminescent Yb(III) compounds known in
      water, and this ligand appears to be suitable for the development of NIR probes
      for bioanalyses.

PMID- 16411710
TI  - Unligated diruthenium(II,II) tetra(trifluoroacetate): the first X-ray structural
      study, thermal compressibility, Lewis acidity, and magnetism.
AB  - The title compound, [Ru(2)(O(2)CCF(3))(4)] (1), has been obtained without any
      exogenous ligands and crystallized by deposition from the gas phase at 170
      degrees C. Its crystal structure has been determined for the first time to
      confirm an infinite chain motif built on axial Ru...O interactions of the
      diruthenium(II,II) units. The X-ray diffraction studies at variable temperatures
      showed no phase transitions in the range of 295-100 K but revealed a significant
      decrease in the volume per atom from 14.2 to 13.3 A(3). This noticeable thermal
      compressibility effect is discussed in connection with the solid-state packing of
      the [Ru(2)(O(2)CCF(3))(4)](infinity) chains. The highly electrophilic character
      of the diruthenium(II,II) units has been shown by the gas-phase deposition
      reaction of [Ru(2)(O(2)CCF(3))(4)] with an aromatic donor substrate, namely
      [2.2]paracyclophane (C(16)H(16)). As a result of the above reaction, a new arene
      adduct [Ru(2)(O(2)CCF(3))(4).C(16)H(16)] (2) has been isolated in crystalline
      form. It has an extended one-dimensional (1D) chain structure comprised of
      alternating building units and based on the rare bridging mode of
      [2.2]paracyclophane, [Ru(2)(O(2)CCF(3))(4).(mu(2)-eta(2):eta(2)
      C(16)H(16))](infinity). The magnetic susceptibility of 1 and 2 has been measured
      and compared in the range of 1.8-300 K. In addition, in the course of synthesis
      of 1 by the carboxylate exchange reactions, a new mixed-carboxylate
      diruthenium(II,II) core complex [Ru(2)(O(2)CCF(3))(3)(O(2)CC(2)H(5))] (3),
      bearing no exogenous ligands, has also been isolated and structurally
      characterized. It exhibits an interesting polymeric structure in which the
      ruthenium(II) centers selectively form axial interdimer contacts with the O-atoms
      of the propionate groups only.

PMID- 16411711
TI  - Complexes of cytotoxic chelators from the dipyridyl ketone isonicotinoyl
      hydrazone (HPKIH) analogues.
AB  - In an effort to better understand the antiproliferative effects of the tridentate
      hydrazone chelators di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and di-2
      pyridyl ketone benzoyl hydrazone (HPKBH), we report the coordination chemistry of
      these ligands with the divalent metal ions, Mn, Co, Ni, Cu, and Zn. These
      complexes are compared with their Fe(II) analogues which were reported
      previously. The crystal structures of Co(PKIH)(2), Ni(PKIH)(2), Cu(PKIH)(2),
      Mn(PKBH)(2), Ni(PKBH)(2), Cu(PKBH)(2), and Zn(PKBH)(2) are reported where similar
      bis-tridenate coordination modes of the ligands are defined. In pure DMF, all
      complexes except the Zn(II) compounds exhibit metal-centered M(III/II) (Mn, Fe,
      Co, Ni) or M(II/I) (Cu) redox processes. All complexes show ligand-centered
      reductions at low potential. Electrochemistry in a mixed water/DMF solvent only
      elicited metal-centered responses from the Co and Fe complexes. Remarkably, all
      complexes show antiproliferative activity against the SK-N-MC neuroepithelioma
      cell line similar to (HPKIH) or significantly greater than that of the (HPKBH)
      ligand which suggests a mechanism that does not only involve the redox activity
      of these complexes. In fact, we suggest that the complexes act as lipophilic
      transport shuttles that allow entrance to the cell and enable the delivery of
      both the ligand and metal which act in concert to inhibit proliferation.

PMID- 16411712
TI  - Tetrakis(dimethyltin)-containing tungstophosphate [{Sn(CH3)2}4(H2P4W24O92)2]28-:
      first evidence for a lacunary Preyssler ion.
AB  - We demonstrate for the first time that the superlacunary polyanion
      [H(2)P(4)W(24)O(94)](22)(-) reacts with electrophiles. One-pot reaction of this
      precursor polyanion with dimethyltin dichloride in aqueous acidic medium results
      in the hybrid organic-inorganic [{Sn(CH(3))(2)}(4)(H(2)P(4)W(24)O(92))(2)](28)(-)
      (1). Single-crystal X-ray analysis was carried out on
      K(17)Li(11)[{Sn(CH(3))(2)}(4)(H(2)P(4)W(24)O(92))(2)].51H(2)O (1a), which
      crystallizes in the tetragonal system, space group P4(2)/nmc, a = b = 21.5112(17)
      and c = 27.171(3) A, and Z = 2. Polyanion 1 is composed of two (P(4)W(24)O(92))
      fragments that are linked by four equivalent diorganotin groups. The
      unprecedented assembly 1 has D(2)(d)() symmetry and contains a hydrophobic pocket
      in the center of the molecule. The cyclic voltammetry pattern of 1 is constituted
      by a first broad, 16-electron reduction wave followed by a second large current
      intensity wave. No splitting of the first reduction wave could be obtained at
      moderate scan rate values, even though two well-separated oxidation processes are
      associated with it. The characteristics of the first wave are clearly different
      from those obtained for the polyanion precursor [H(2)P(4)W(24)O(94)](22)(-) and
      the related, wheel-shaped [H(7)P(8)W(48)O(184)](33)(-), which is due to the
      {Sn(CH(3))(2)} fragments in 1. However, no feature was observed in the
      voltammogram which could be associated with reduction of the Sn centers.

PMID- 16411713
TI  - Strong electronic interaction between two dimolybdenum units linked by a
      tetraazatetracene.
AB  - The large rigid dianion fluoflavinate, C(14)H(8)N(4)(2)(-), consisting of four
      fused and planar six-membered rings with four nitrogen donor atoms, has been used
      to link two metal-to-metal bonded and redox-active Mo(2)(n)()(+) units which are
      each locally bridged by three additional groups, collectively denoted [Mo(2)]. In
      1, the [Mo(2)] units are Mo(2)(DAniF)(3) (DAniF = N,N'-di-p-anisylformamidinate),
      and in 5, they are trans-Mo(2)(DAniF)(2)(O(2)CCH(3)) groups. These
      [Mo(2)](fluoflavinate)[Mo(2)] compounds show three reversible one-electron
      oxidation steps, one more than all other [Mo(2)](linker)[Mo(2)] species known to
      date. The first two redox processes are metal-based, and the third one has been
      assigned to a ligand oxidation by comparison to that of paddlewheel compound 4
      which contains only one dimolybdenum unit with a monoanionic fluoflavinate
      ligand. Chemical oxidations of 1 produce the singly- and doubly-oxidized species
      2 and 3, respectively. All compounds have been characterized by X-ray
      crystallography and, as appropriate, by various techniques such as NMR, EPR, near
      IR, and UV-vis. The fluoflavinate ligand strongly mediates electronic
      communication between the dimetal units, and the mixed valence species 2 can be
      described as electronically delocalized. Calculations at the DFT level using a
      variety of functionals support such an assignment and indicate that a strong
      transition in the NIR for the singly oxidized species can be assigned to the HOMO
      1 to SOMO transition.

PMID- 16411714
TI  - Luminescence detection of transition and heavy metals by inversion of excited
      states: synthesis, spectroscopy, and X-ray crystallography of Ca, Mn, Pb, and Zn
      complexes of 1,8-anthraquinone-18-crown-5.
AB  - A lumophore composed of anthraquinone attached to a macrocyclic polyether ring
      containing an intraannular carbonyl is capable of selectively detecting Pb(2+)()
      ion in solution using an alternative photophysical detection mechanism. Of the
      various methods available for detection of ions in solution, a mechanism
      involving inversion of excited states has not been previously employed for the
      detection of transition and heavy metals. In this mechanism, nonradiative n-pi
      transitions are replaced by radiative pi-pi transitions upon complexation by a
      suitable guest cation. Optimum fluorescence enhancement is achieved using cations
      of high charge, large cations that form long bonds within the host, and cations
      which do not coordinate solvent or the counteranion, all of which are necessary
      for inversion of excited states to occur. Photophysical properties and binding
      constants of this new class of luminescence sensors are provided, as well as the
      X-ray crystallographic results for Pb(2+), Mn(2+), and Zn(2+) complexes of 1,8
      oxybis(ethylene-oxyethyleneoxy)anthracene-9,10-dione (1), referred to as 1,8
      anthraquinone-18-crown-5. ([1.Pb](ClO(4))(2) (2) (monoclinic, P21/n, a =
      8.0303(6) A, b = 25.976(2) A, c = 12.1616(9) A, beta = 94.956(1) degrees , Z = 4,
      4980 reflections [I > or = 2sigma(I)], R1 = 0.0266, wR2, 0.0500, 173(2) K).
      [1.Mn(H(2)O)(NCCH(3))](ClO(4))(2) (5) (monoclinic, P21/c, a = 10.132(2) A, b =
      11.8030(4) A, c = 23.999(7) A, beta = 95.75(2) degrees , Z = 4, 3000 reflections
      [I > or = 2sigma(I)], R1 = 0.0488, wR2, 0.0938, 203(2) K).
      [1.Zn(H(2)O)(NCCH(3))](ClO(4))(2) (6) (monoclinic, P21/c, a = 10.177(10) A, b =
      11.977(6) A, c = 24.166(4) A, beta = 95.83(4) degrees , Z = 4, 3061 reflections
      [I > or = 2sigma(I)], R1 = 0.0673, wR2, 0.1729, 295(2) K).).

PMID- 16411716
TI  - Syntheses and structures of strontium, barium, and europium
      bis(diphosphanylamido) complexes.
AB  - Bis(diphosphanylamido) complexes of strontium and europium,
      [{(Ph(2)P)(2)N}(2)M(THF)(3)] (M = Sr (1), Eu (2)), have been prepared by reaction
      of [K(THF)(n)()][N(PPh(2))(2)] (n = 1.25, 1.5) and MI(2). The single-crystal X
      ray structures of compounds 1 and 2 always show a eta(2) coordination of the
      ligand via the nitrogen and one phosphorus atom. In solution, a dynamic behavior
      of the ligand is observed, which is caused by the rapid exchange of the two
      different phosphorus atoms. As a result of the radius of the larger ion,
      treatment of [K(THF)(n)()][N(PPh(2))(2)] with BaI(2) gives the coordination
      polymer [{(Ph(2)P)(2)N}(2)Ba(THF){(Ph(2)P)(2)N}K](n)() (3). Two of the three
      {(Ph(2)P)(2)N}(-) ligands of compound 3 bind to the metal in eta(2) (N, P) while
      the third shows a heteroallylic (P, P) coordination mode. In the solid state, the
      infinite chain is formally held together by pi coordination of the phenyl rings
      to the potassium atoms.

PMID- 16411715
TI  - DFT-INDO/S modeling of new high molar extinction coefficient charge-transfer
      sensitizers for solar cell applications.
AB  - A new ruthenium(II) complex, tetrabutylammonium [ruthenium (4-carboxylic acid-4'
      carboxylate-2,2'-bipyridine)(4,4'-di(2-(3,6-dimethoxyphenyl)ethenyl)-2,2'
      bipyridine)(NCS)(2)] (N945H), was synthesized and characterized by analytical,
      spectroscopic, and electrochemical techniques. The absorption spectrum of the
      N945H sensitizer is dominated by metal-to-ligand charge-transfer (MLCT)
      transitions in the visible region, with the lowest allowed MLCT bands appearing
      at 25 380 and 18 180 cm(-1). The molar extinction coefficients of these bands are
      34 500 and 18 900 M(-1) cm(-1), respectively, and are significantly higher when
      compared to than those of the standard sensitizer cis-dithiocyanatobis(4,4'
      dicarboxylic acid-2,2'-bipyridine)ruthenium(II). An INDO/S and density functional
      theory study of the electronic and optical properties of N945H and of N945
      adsorbed on TiO(2) was performed. The calculations point out that the top three
      frontier-filled orbitals have essentially ruthenium 4d (t(2g) in the octahedral
      group) character with sizable contribution coming from the NCS ligand orbitals.
      Most critically the calculations reveal that, in the TiO(2)-bound N945
      sensitizer, excitation directs charge into the carboxylbipyridine ligand bound to
      the TiO(2) surface. The photovoltaic data of the N945 sensitizer using an
      electrolyte containing 0.60 M butylmethylimidazolium iodide, 0.03 M I(2), 0.10 M
      guanidinium thiocyanate, and 0.50 M tert-butylpyridine in a mixture of
      acetonitrile and valeronitrile (volume ratio = 85:15) exhibited a short-circuit
      photocurrent density of 16.50 +/- 0.2 mA cm(-2), an open-circuit voltage of 790
      +/- 30 mV, and a fill factor of 0.72 +/- 0.03, corresponding to an overall
      conversion efficiency of 9.6% under standard AM (air mass) 1.5 sunlight, and
      demonstrated a stable performance under light and heat soaking at 80 degrees C.

PMID- 16411717
TI  - Quantum chemistry predicts multiply bonded diuranium compounds to be stable.
AB  - Results from quantum chemical calculations that predict the existence of a series
      of diuranium molecules are reported. Two diuranium chlorides, U(2)Cl(6) and
      U(2)Cl(8)(2)(-), and three different carboxylates, U(2)(OCHO)(4), U(2)(OCHO)(6),
      and U(2)(OCHO)(4)Cl(2) have been studied. All species have been found to be
      stable with a multiply bonded U(2) unit.

PMID- 16411718
TI  - Thermal aqueous solution approach for the synthesis of triangular and hexagonal
      gold nanoplates with three different size ranges.
AB  - The synthesis of gold nanoplates was carried out in an aqueous solution by
      thermal reduction of HAuCl(4) with trisodium citrate in the presence of
      cetyltrimethylammonium bromide (CTAB) surfactant in just 5-40 min. The sizes of
      the gold nanoplates can be varied from as small as tens of nanometers in width,
      to several hundreds of nanometers, and even a few microns in width by changing
      the reagent concentrations, solution temperature, and the reaction time. A
      [CTAB]/[HAuCl(4)] ratio of 6 in the reaction solution was found to be favorable
      for the formation of gold nanoplates. The nanoplates possess well-defined shapes
      with sharp edges. The small nanoplates exhibit mainly a triangular shape, while
      larger nanoplates show a mixture of triangular, hexagonal, truncated triangular,
      and other symmetrical structures. The nanoplates are composed of essentially
      (111) lattice planes, as revealed by both XRD and TEM results. Nanoplates with
      widths from several hundreds of nanometers to a few microns absorb light strongly
      in the near-infrared region. The growth mechanism of these nanoplates was
      investigated. The ability to synthesize gold nanoplates with these different size
      ranges in large scale in aqueous solution using simple CTAB capping surfactant
      should allow more diverse applications of gold nanoplates.

PMID- 16411719
TI  - Aqueous ferryl(IV) ion: kinetics of oxygen atom transfer to substrates and oxo
      exchange with solvent water.
AB  - The aqueous iron(IV) ion, Fe(IV)(aq)O(2+), generated from O(3) and Fe(aq)(2+),
      reacts rapidly with various oxygen atom acceptors (sulfoxides, a water-soluble
      triarylphosphine, and a thiolatocobalt complex). In each case, Fe(IV)(aq)O(2+) is
      reduced to Fe(aq)(2+), and the substrate is oxidized to a product expected for
      oxygen atom transfer. Competition methods were used to determine the kinetics of
      these reactions, some of which have rate constants in excess of 10(7) M(-1) s(
      1). Oxidation of dimethyl sulfoxide (DMSO) has k = 1.26 x 10(5) M(-1) s(-1) and
      shows no deuterium kinetic isotope effect, k(DMSO-d(6)) = 1.23 x 10(5) M(-1) s(
      1). The Fe(IV)(aq)O(2+)/sulfoxide reaction is the product-forming step in a very
      efficient Fe(aq)(2+)-catalyzed oxidation of sulfoxides by ozone. This catalytic
      cycle, combined with labeling experiments in H(2)(18)O, was used to determine the
      rate constant for the oxo-group exchange between Fe(IV)(aq)O(2+) and solvent
      water under acidic conditions, k(exch) = 1.4 x 10(3) s(-1).

PMID- 16411720
TI  - Structure and properties of Dinuclear [RuII([n]aneS4)] complexes of 3,6-Bis(2
      pyridyl)-1,2,4,5-tetrazine.
AB  - The synthesis of dinuclear [Ru(II)([n]aneS(4))] (where n = 12, 14) complexes of
      the bridging ligand 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine are reported. The X-ray
      structures of both of the new complexes are compared to a newly obtained
      structure for a dinuclear [Ru(II)([9]aneS(3))]-based analogue, whose synthesis
      has previously been reported. A comparison of the electrochemistry of the three
      complexes reveals that the first oxidation of the [Ru(II)([n]aneS(4))]-based
      systems is a ligand-based couple, indicating that the formation of the radical
      anion form of the bridging ligand is stabilized by metal center coordination.
      Spectroelectrochemistry studies on the mixed-valence form of the new complexes
      suggest that they are Robin and Day Class II systems. The electrochemical and
      electronic properties of these complexes is rationalized by a consideration of
      the pi-bonding properties of thiacrown ligands.

PMID- 16411721
TI  - Synthesis, characterization, and preliminary oxygenation studies of benzyl- and
      ethyl-substituted pyridine ligands of carboxylate-rich diiron(II) complexes.
AB  - In this study benzyl and ethyl groups were appended to pyridine and aniline
      ancillary ligands in diiron(II) complexes of the type [Fe(2)(mu
      O(2)CAr(R))(2)(O(2)CAr(R))(2)(L)(2)], where (-)O(2)CAr(R) is a sterically
      hindered terphenyl carboxylate, 2,6-di(p-tolyl)- or 2,6-di(p
      fluorophenyl)benzoate (R = Tol or 4-FPh, respectively). These
      crystallographically characterized compounds were prepared as analogues of the
      diiron(II) center in the hydroxylase component of soluble methane monooxygenase
      (MMOH). The use of 2-benzylpyridine (2-Bnpy) yielded doubly bridged [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(2-Bnpy)(2)] (1) and [Fe(2)(mu-O(2)CAr(4)(
      )(FPh))(2)(O(2)CAr(4)(-)(FPh))(2)(2-Bnpy)(2)] (4), whereas tetra-bridged
      [Fe(2)(mu-O(2)CAr(Tol))(4)(4-Bnpy)(2)] (3) resulted when 4-benzylpyridine (4
      Bnpy) was employed. Similarly, 2-(4-chlorobenzyl)pyridine (2-(4-ClBn)py) and 2
      benzylaniline (2-Bnan) were employed as N-donor ligands to prepare [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(2-(4-ClBn)py)(2)] (2) and [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(2-Bnan)(2)] (5). The placement of the
      substituent on the pyridine ring had no effect on the geometry of the diiron(II)
      compounds isolated when 2-, 3-, or 4-ethylpyridine (2-, 3-, or 4-Etpy) was
      introduced as the ancillary nitrogen ligand. The isolated [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(2-Etpy)] (6), [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(3-Etpy)] (7), [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(4-Etpy)] (8), and [Fe(2)(mu-O(2)CAr(4)(
      FPh))(2)(O(2)CAr(4)(-)(FPh))(2)(2-Etpy)(2)] (9) complexes all contain doubly
      bridged metal centers. The oxygenation of compounds 1-9 was studied by GC-MS and
      NMR analysis of the organic fragments following decomposition of the product
      complexes. Hydrocarbon fragment oxidation occurred for compounds in which the
      substrate moiety was in close proximity to the diiron center. The extent of
      oxidation depended upon the exact makeup of the ligand set.

PMID- 16411723
TI  - Metal-metal interactions in thallium(I)/platinum(II) compounds involving a
      chelating dicarbene and various auxiliary ligands.
AB  - Reaction of Tl(I)NO(3) and (C(4)H(10)N(4))Pt(II)(mnt) or
      (C(4)H(10)N(4))Pt(II)(dmg-H) [mnt = maleonitriledithiolate, dmg-H =
      dimethylglyoximate dianion] in dilute, aqueous KOH yielded adducts of Tl(I) and
      the conjugate bases of the platinum(II) compounds. The compound
      Tl(I)[(C(4)H(9)N(4))Pt(II)(dmg-H)].5H(2)O forms as dimers with close
      Tl(I)...Pt(II) separations of 3.0843(5) A, while Tl(I)[(C(4)H(9)N(4))Pt(II)(mnt)]
      has much longer Tl(I)...Pt(II) separations of 3.4400(2) A and forms loosely
      associated, helical coordination polymers. The new compounds are compared with
      the red and yellow polymorphs of Tl(I)[(C(4)H(9)N(4))Pt(II)(CN)(2)], and the
      influences of crystal packing forces, Coulombic interactions, and hydrogen
      bonding on supramolecular structures and Tl(I)...Pt(II) separations are
      discussed.

PMID- 16411722
TI  - Dioxygen-initiated oxidation of heteroatomic substrates incorporated into
      ancillary pyridine ligands of carboxylate-rich diiron(II) complexes.
AB  - Progress toward the development of functional models of the carboxylate-bridged
      diiron active site in soluble methane monooxygenase is described in which
      potential substrates are introduced as substituents on bound pyridine ligands.
      Pyridine ligands incorporating a thiol, sulfide, sulfoxide, or phosphine moiety
      were allowed to react with the preassembled diiron(II) complex [Fe(2)(mu
      O(2)CAr(R))(2)(O(2)CAr(R))(2)(THF)(2)], where (-)O(2)CAr(R) is a sterically
      hindered 2,6-di(p-tolyl)- or 2,6-di(p-fluorophenyl)benzoate (R = Tol or 4-FPh).
      The resulting diiron(II) complexes were characterized crystallographically.
      Triply and doubly bridged compounds [Fe(2)(mu-O(2)CAr(Tol))(3)(O(2)CAr(Tol))(2
      MeSpy)] (4) and [Fe(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(2-MeS(O)py)(2)] (5)
      resulted when 2-methylthiopyridine (2-MeSpy) and 2-pyridylmethylsulfoxide (2
      MeS(O)py), respectively, were employed. Another triply bridged diiron(II)
      complex, [Fe(2)(mu-O(2)CAr(4)(-)(FPh))(3)-(O(2)CAr(4)(-)(FPh))(2-Ph(2)Ppy)] (3),
      was obtained containing 2-diphenylphosphinopyridine (2-Ph(2)Ppy). The use of 2
      mercaptopyridine (2-HSpy) produced the mononuclear complex [Fe(O(2)CAr(Tol))(2)(2
      HSpy)(2)] (6a). Together with that of previously reported [Fe(2)(mu
      O(2)CAr(Tol))(3)(O(2)CAr(Tol))(2-PhSpy)] (2) and [Fe(2)(mu
      O(2)CAr(Tol))(3)(O(2)CAr(Tol))(2-Ph(2)Ppy)] (1), the dioxygen reactivity of these
      iron(II) complexes was investigated. A dioxygen-dependent intermediate (6b)
      formed upon exposure of 6a to O(2), the electronic structure of which was probed
      by various spectroscopic methods. Exposure of 4 and 5 to dioxygen revealed both
      sulfide and sulfoxide oxidation. Oxidation of 3 in CH(2)Cl(2) yields [Fe(2)(mu
      OH)(2)(mu-O(2)CAr(4)(-)(FPh))(O(2)CAr(4)(-FPh))(3)(OH(2))(2-Ph(2)P(O)py)] (8),
      which contains the biologically relevant {Fe(2)(mu-OH)(2)(mu-O(2)CR)}(3+) core.
      This reaction is sensitive to the choice of carboxylate ligands, however, since
      the p-tolyl analogue 1 yielded a hexanuclear species, 7, upon oxidation.

PMID- 16411724
TI  - The effect of the diphosphine basicity on the excited-state properties of trans
      (N2)2W(R2PCH2CH2PR2)2: identification of near-degenerate, luminescent 3MLCT and
      3LF terms.
AB  - Absorption spectra (77 and 298 K), luminescence spectra (5-80 K), and
      luminescence lifetimes (5-80 K) for the title complexes have been correlated to
      increasing diphosphine basicity (R = 4-CF(3)-Ph < 4-H-Ph < 4-CH(3)O-Ph < Et). As
      a consequence, spectral peaks have been assigned to (1,3)MLCT (B(1u), W -->
      phosphorus) and (1,3)LF (B(2g)) terms. As the ligand basicity increases, the
      (3)MLCT bands observed in absorption blue-shift nearly 8000 cm(-1) and the
      vibrationally structured (3)LF bands observed in emission red-shift approximately
      1300 cm(-1). (3)LF terms lie lowest in energy in the 4-H-Ph, 4-CH(3)O-Ph, and Et
      compounds, and temperature-dependent lifetime data suggest emission from each be
      assigned to the equilibrated, spin-orbit split levels of the (3)LF term. The
      (3)LF and (3)MLCT excited-state terms lie close in energy in the 4-CF(3)-Ph
      compound, resulting in an emission band shape that is temperature-dependent. At
      77 K, the emission band is broad and structureless and is assigned to arise
      primarily from the (3)MLCT term. As the temperature is lowered toward 5 K, the
      (3)MLCT emission diminishes in intensity accompanied by the development of a
      vibrational structure that is characteristic of emission from the (3)LF term.
      These excited-state terms satisfy the requirements (different orbital origins,
      near-degeneracy) for separation by a Franck-Condon energy barrier, resulting in
      simultaneous emission from both terms between 5 and 77 K.

PMID- 16411725
TI  - Five new manganese-mu-azido 2D compounds synthesized in aqueous hydrazoic acid
      from pyrazine derivatives.
AB  - The syntheses, structural characterization, and magnetic behavior of five new 2D
      manganese(II) complexes with empirical formulas [Mn(N(3))(2)(2,6
      DiMepyz)(H(2)O)](n)() (1), [Mn(N(3))(2)(Etpyz)(H(2)O)](n)() (2),
      [Mn(N(3))(2)(H(2)O)(2)](n)()(2,3-DiMepyz)(n)() (3), [Mn(N(3))(2)(Clpyz)(2)](n)()
      (4), and [Mn(N(3))(2)(Ipyz)(2)](n)() (5) (pyz = pyrazine (1,4-diazine)) are
      reported. 1 crystallizes in the monoclinic system, space group P2(1)/c, with unit
      cell parameters a = 7.513(4) A, b = 17.438(7) A, c = 8.404(4) A, beta = 94.53(4)
      degrees , and Z = 4. 2 crystallizes in the triclinic system, space group P, with
      unit cell parameters a = 7.386(2) A, b = 8.434(2) A, c = 9.442(3) A, alpha =
      71.82(2) degrees , beta = 72.08(2) degrees , gamma = 88.54(2) degrees , and Z =
      2. 3 crystallizes in the monoclinic system, space group C2/c, with unit cell
      parameters a = 20.438(7) A, b = 7.711(2) A, c = 7.457(2) A, beta = 93.76(3)
      degrees , and Z = 4. 4 crystallizes in the orthorhombic system, space group Pbca,
      with unit cell parameters a = 8.600(2) A, b = 13.440(4) A, c = 24.083(7) A, and Z
      = 8. 5 crystallizes in the orthorhombic system, space group Pbca, with unit cell
      parameters a = 8.521(2) A, b = 13.787(3) A, c = 26.237(5) A, and Z = 8. The
      compounds 1-5 have only azido bridging ligands. In 1-3 each manganese atom is
      linked to the four nearest neighbors by only end-to-end azido bridges, forming
      square layers. 4 and 5 show alternating end-to-end and end-on azido bridges
      between manganese atoms. The magnetic properties of 1-5 are reported. At high
      temperatures the plots of chi(M) or chi(M)T vs T for the 1-3 compounds can be
      fitted as homogeneous 2D systems with J = -4.9, -4.4, and -3.9 cm(-)(1) for 1-3,
      respectively. For 1, 3, and 5 magnetic ordering and spontaneous magnetizations is
      achieved below T(c) = 35, 29, and 22 K, respectively, whereas 2 and 4 do not show
      spontaneous magnetization up to 2 K.

PMID- 16411726
TI  - A windmill-shaped hexacopper(II) molecule built up by template core-controlled
      expansion of diaquatetrakis(mu2-adeninato-N3,N9)dicopper(II) with
      aqua(oxydiacetato)copper(II).
AB  - The windmill-shaped hexanuclear copper(II) cluster {(H(2)O)(2)Cu(2)(mu(3)
      (Ade)(4)[Cu(oda)(H(2)O)](4)}.6H(2)O (1-o) has been synthesized in aqueous medium
      by in situ core-controlled expansion of the neutral building block Cu(2)(mu(2)
      N3,N9-Ade)(4)(H(2)O)(2) (2) with Cu(oda)(H(2)O) (3-o) (Ade = adeninato(1-) and
      oda = oxydiacetato(2-) ligands). Crystal data for 2-b (2.5H(2)O): triclinic,
      space group P(-)1; a = 9.374(1), b = 9.440(1), c = 10.326(1) A; alpha = 78.72(1),
      beta = 76.77(1), gamma = 63.51(1) degrees ; final R(1) = 0.059; T = 100(2) K.
      Crystal data for 1-o: monoclinic, space group P2(1)/n; a = 15.203(2), b =
      10.245(1), c = 19.094(2) A; beta = 101.61(1) degrees ; final R(1) = 0.049; T =
      293(2) K. The X-shaped hexanuclear molecule consists of a central core (2) and
      four terminal arms (3-o) linked together by bridging mu(3)-N3,N7,N9-Ade ligands.
      There are three crystallographic independent metal atoms (two terminals, one
      central). All Cu(II) atoms exhibit a 4 + 1 coordination, of which one is an aqua
      apical ligand. The basal coordination sets complete the CuN(4) + O or CuO(3)N + O
      chromophores for the central or terminal metal atoms, respectively. Thermal
      stability and spectral and magnetic properties were also studied. Analogous
      compounds to 1-o with tridentate or tripodal tetradentate ligands L(2-), instead
      of oda, have also been synthesized.

PMID- 16411727
TI  - Synthesis and crystal and electronic structures of the Na2(Sc4Nb2)(Nb6O12)3
      octahedral niobium cluster oxide. Structural correlations between AnBM6L12(Z)
      series and Chevrel Phases.
AB  - We report here the synthesis and crystal and electronic structures of the
      Na(2)(Sc(4)Nb(2))(Nb(6)O(12))(3) niobium oxide whose structure is related to that
      of Ti(2)Nb(6)O(12). It constitutes a new member of the larger A(n)()BM(6)L(12)(Z)
      families (A = monovalent cation located in tetrahedral cavities of units, B =
      monovalent or trivalent cations located in octahedral cavities of units, M = rare
      earth, Zr, or Nb, Z = interstitial except for M = Nb). The structural
      relationships between the A(n)BM(6)L(12)(Z) series (M(6)L(i)(12)L(a)(6) unit
      based compounds with a M(6)L(i)(6)L(i-a)(6/2)L(a-i)(6/2) cluster framework) and
      Chevrel Phases (M(6)L(i)(8)L(a)(6) unit-based compounds with a M(6)L(i)(2)L(i
      a)(6/2)L(a-i)(6/2) cluster framework) are shown in terms of M(6)L(18) and
      M(6)L(14) unit packing. Despite a topology similar to that encountered in Chevrel
      Phases, intercalation properties are not expected in the Nb(6)O(i)(6)O(i
      a)(6/2)O(a-i)(6/2) cluster framework-based compounds. Finally, it is shown, from
      theoretical LMTO calculations, that a semiconducting behavior is expected for a
      maximum VEC of 14 in the Nb(6)O(i)(6)O(i-a)(6/2)O(a-i)(6/2) cluster framework.

PMID- 16411728
TI  - O-atom-transfer oxidation of [molybdenum(IV) oxo{3,6-(acylamino)2- 1,2
      benzenedithiolato}2]2- promoted by intramolecular NH...S hydrogen bonds.
AB  - Novel molybdenum dithiolene compounds having neighboring amide groups as models
      for molybdoenzymes, (NEt(4))(2)[Mo(IV)O{1,2-S(2)-3,6-(RCONH)(2)C(6)H(2)}(2)] (R =
      CH(3), CF(3), t-Bu, Ph(3)C), were designed and synthesized. The contributions of
      the NH...S hydrogen bond to the electrochemical properties of the metal ion and
      the reactivity of the O-atom-transfer reaction were investigated by a comparison
      with [Mo(IV)O(1,2-S(2)C(6)H(4))(2)](2)(-). The MoOS(4) core of [Mo(IV)O{1,2-S(2)
      3,6-(CH(3)CONH)(2)C(6)H(2)}(2)](2)(-) shows no significant geometrical difference
      from that of [Mo(IV)O(1,2-S(2)C(6)H(4))(2)](2)(-) in the crystal. The hydrogen
      bonds positively shifted the Mo(IV/V) redox potential and accelerated the
      reduction of Me(3)NO.

PMID- 16411730
TI  - Yttrium and lanthanide complexes having a chiral phosphanylamide in the
      coordination sphere.
AB  - The chiral phosphanylamides {N(R-CHMePh)(PPh(2))}(-) and {N(S-CHMePh)(PPh(2))}(-)
      were introduced into rare earth chemistry. Transmetalation of the enantiomeric
      pure lithium compounds Li{N(R-CHMePh)(PPh(2))} (1a) and Li{N(S-CHMePh)(PPh(2))}
      (1b) with lanthanide bis(phosphinimino)methanide dichloride
      [{CH(PPh(2)NSiMe(3))(2)}LnCl(2)](2) in a 2:1 molar ratio in THF afforded the
      enantiomeric pure complexes [{CH(PPh(2)NSiMe(3))(2)}Ln(Cl){eta(2)-N(R
      CHMePh)(PPh(2))}] (Ln = Er (2a), Yb (3a), Lu (4a)) and
      [{CH(PPh(2)NSiMe(3))(2)}Ln(Cl){eta(2)-N(S-CHMePh)(PPh(2))}] (Ln = Er (2b), Yb
      (3b), Lu (4b)). The solid-state structures of 2a and 3a,b were established by
      single-crystal X-ray diffraction. Attempts to synthesize compounds 3 in a one-pot
      reaction starting from K{CH(PPh(2)NSiMe(3))(2)}, YbCl(3), and 1 resulted in the
      lithium chloride incorporated complex [{(Me(3)SiNPPh(2))(2)CH}Yb(mu
      Cl)(2)LiCl(THF)(2)] (5). In an alternative approach to give chiral rare earth
      compounds in a one-pot reaction 1a or 1b was reacted with LnCl(3) and
      K(2)C(8)H(8) to give the enantiomeric pure cyclooctatetraene compounds [{eta(2)
      N(R-CHMePh)(PPh(2))}Ln(eta(8)-C(8)H(8))] (Ln = Y (6a), Er (7a), Yb (8)) and
      [{eta(2)-N(S-CHMePh)(PPh(2))}Ln(eta(8)-C(8)H(8))] (Ln = Y (6b), Er (7b)). The
      structures of 6a,b, 7a, and 8 were confirmed by single-crystal X-ray diffraction
      in the solid state.

PMID- 16411729
TI  - Oxorhenium(V) and oxotechnetium(V) [NN][S]3 complexes of 2-phenylbenzothiazole
      derivatives.
AB  - The reaction of 2-(2'-pyridyl)benzothiazole, [NN], with the ReO(V)(3+) and
      TcO(V)(3+) cores in the presence of thiophenols, [S] (RC(6)H(4)SH, R = H, 4
      CH(3), 4-OCH(3)), as coligands led to the isolation of hexacoordinated complexes
      of the MO[NN][S](3) type (M = Re, Tc). In all cases, two geometric mer isomers
      were formed, as evidenced by NMR spectroscopy and confirmed by X-ray
      crystallography. In both isomers, the coordination geometry about the metal ion
      is a distorted octahedral defined by the two nitrogen atoms of the bidentate
      ligand, the three sulfur atoms of the monodentate thiols, and the oxygen atom of
      the oxo group. The apical positions of the octahedron are occupied by the oxygen
      of the oxo group and, in one of the isomers, the nitrogen of the pyridyl moiety
      of 2-(2'-pyridyl)benzothiazole, while, in the second isomer, the imine nitrogen
      of 2-(2'-pyridyl)benzothiazole. The complexes are stable, neutral, and
      lipophilic. Complete (1)H and (13)C NMR assignments are reported for all
      complexes. The synthetic reaction was also successfully transferred at the
      technetium-99m tracer level by ligand exchange reaction using (99m)Tc
      glucoheptonate as precursor in the presence of 2-(2'-pyridyl)benzothiazole and 4
      CH(3)C(6)H(4)SH. The structure of the technetium-99m complex was established by
      high-performance liquid chromatographic comparison with the analogous
      oxotechnetium and oxorhenium complexes. The 2-(2'-pyridyl)benzothiazole ligand
      serves as a preliminary model for 2-(4-aminophenyl)benzothiazole, which possesses
      interesting properties for the development of technetium and rhenium
      radiopharmaceuticals for tumor imaging and/or radiotherapy as well as in vivo
      diagnosis of Alzheimer's disease.

PMID- 16411731
TI  - Design of a new family of inorganic compounds Ae2F2SnX3 (Ae = Sr, Ba; X = S, Se)
      using rock salt and fluorite 2D building blocks.
AB  - We could predict the structure of a new family of compounds Ae(2)F(2)SnX(3) (Ae =
      Sr, Ba; X = S, Se) from the stacking of known 2D building blocks of the rock salt
      and fluorite types. With a high-temperature ceramic method we have then succeeded
      to synthesize the four compounds Ba(2)F(2)SnS(3), Ba(2)F(2)SnSe(3),
      Sr(2)F(2)SnS(3), and Sr(2)F(2)SnSe(3). The structure refinements from X-ray
      powder diffraction patterns have confirmed the structure predictions and showed
      their good accuracy. The structure of the four compounds results from the
      alternated stacking of fluorite [Ae(2)F(2)] (Ae = Sr, Ba) and distorted rock salt
      [SnX(3)] (X = S, Se) 2D building blocks. As shown by band structure calculations,
      these blocks behave as a charge reservoir and a charge acceptor, respectively.
      Sr(2)F(2)SnS(3) and Ba(2)F(2)SnS(3) are transparent with optical gaps of 3.06 and
      3.21 eV, respectively. However, an attempt to obtain a transparent conductor by
      substituting Ba per La in Ba(2)F(2)SnS(3) was unsuccessful.

PMID- 16411732
TI  - Effect of constrained donor atom orientations on the stabilities, complexation
      kinetics, redox potentials, and structures of macrocyclic polythiaether
      Complexes. Copper(II) complexes with cyclopentanediyl derivatives of [14]aneS4 in
      80% methanol.
AB  - The two ethylene bridges in the macrocyclic tetrathiaether 1,4,8,11
      tetrathiacyclotetradecane ([14]aneS(4)) have been systematically replaced by cis-
      or trans-1,2-cyclopentane to generate a series of new ligands that exhibit
      differing preferences for the orientation of the sulfur donor atoms while
      maintaining constant inductive effects. The resulting five dicyclopentanediyl
      derivatives, along with two previously synthesized monocyclopentanediyl
      analogues, have been complexed with Cu(II), and their stability constants,
      formation and dissociation rate constants, and redox potentials have been
      determined in 80% methanol/20% water (by weight). The crystal structures of the
      Cu(II) complexes with the five dicyclopentanediyl-[14]aneS(4) diastereomers as
      well as the structures for a representative Cu(I) complex and one of the free
      ligands have also been determined. The properties of these complexes are compared
      to previous data obtained for the corresponding cyclohexanediyl derivatives in an
      attempt to shed additional light on the influence of sterically constraining
      substituents upon the properties of macrocyclic ligand complexes.

PMID- 16411733
TI  - Variability in the structures of [4-(aminomethyl)pyridine]silver(I) complexes
      through effects of ligand ratio, anion, hydrogen bonding, and pi-stacking.
AB  - The reaction of the asymmetric 4-(aminomethyl)pyridine (4-amp) ligand with
      silver(I) salts of trifluoromethanesulfonate (triflate, OTf(-)), trifluoroacetate
      (tfa(-)), or tetrafluoroborate (BF(4)(-)) have produced a variety of one- and two
      dimensional structural motifs depending upon the ratio in which the components
      are mixed. When the proportion of ligand to metal is 1:1, linear coordination
      polymers are formed with silver(I) OTf(-) (1) and tfa(-) (2). Altering the ratio
      to 2:1, a linear polymer of corner-shared boxes (3) is formed with tfa(-), a
      linear box-in-box "chain link" polymer (4) is formed with OTf(-), and a two
      dimensional sheet (5) is constructed with BF(4)(-). Addition of 5,5'-dimethyl
      2,2'-bipyridine to a solution of 4-ampAgBF(4) disrupts the polymerization of the
      previous structure and results in the construction of the infinite metal-metal
      bound strings of 6a regardless of ratio of amp to silver present. H-bonding, pi
      stacking, and closed-shell Ag-Ag interactions are all involved in the overall
      conformations of the final structures.

PMID- 16411735
TI  - The chain-length dependence test.
AB  - Trends obtained from systematic studies based on chain-length variation have
      provided valuable insight and understanding into the behavior of m-phenylene
      ethynylene foldamers. The generalization of this experimental approach, the chain
      length dependence test, is useful for studying solution conformation, packing in
      the solid state, specific intrachain interactions, and the contributions of end
      groups to a particular property.

PMID- 16411734
TI  - A novel approach to the efficient oxygenation of hydrocarbons under mild
      conditions. Superior oxo transfer selectivity using dioxiranes.
AB  - The design of efficient and general methods for the selective
      oxyfunctionalization of unactivated carbon-hydrogen bonds continues to represent
      a major challenge for the community of chemists, despite the fact that the
      oxidation of alkanes is a major feature of the chemical economy. A low level of
      selectivity is characteristic of large-scale oxidation of hydrocarbons performed
      under customary industrial oxidizing conditions (e.g., the catalytic air
      oxidation of cycloalkanes); in these processes, selectivity is difficult to
      control, because they are often impacted by the usual problems associated with
      free-radical chain reactions. Thus, in the last decades much work has been
      devoted to the search for general methods of selective oxidation that could be
      applied to a variety of satured hydrocarbons. In this context, just a few leading
      methods appear encouraging at the present time. This Account addresses a new
      approach developed in our laboratory, consisting in the application of isolated
      dioxiranes, a class of powerful yet selective oxidants. We contend that the
      method shows promise to contribute resolution of a well-recognized general
      problem in the existing chemistry of alkanes, that is, to achieve efficient
      oxyfunctionalizations with high selectivity for simple as well as structurally
      complex targets.

PMID- 16411736
TI  - Nonadiabatic dynamics of condensed phase rate processes.
AB  - The study of quantum rate processes occurring in condensed phase environments is
      difficult because of the large number of degrees of freedom involved. Since a
      full quantum mechanical treatment is not computationally feasible, one is
      motivated to use mixed quantum-classical dynamical methods. This type of dynamics
      is applicable when one can single out a few degrees of freedom to be quantum in
      nature while treating the remainder classically. We describe a method that is
      based on the quantum-classical Liouville equation, which clearly prescribes the
      details of the coupling between the quantum and classical degrees of freedom.
      With the aid of this machinery, we show how to compute rate constants of
      reactions involving quantum particles immersed in a classical bath. We illustrate
      the use of this method on a model for proton transfer in a molecular complex
      dissolved in a polar solvent.

PMID- 16411737
TI  - Molecular recognition imaging and force spectroscopy of single biomolecules.
AB  - In recent years, considerable attention has focused on biological applications of
      the atomic force microscope (AFM), in particular on high-resolution imaging of
      individual biological molecules and on the measurement of molecular forces under
      near-physiological conditions. The detection of intermolecular forces in the
      piconewton range has paved the way to investigate details on structural
      parameters of the binding pockets and the energy landscapes of many biomolecular
      interactions. The capability of AFM to resolve nanometer-sized details, together
      with its force detection sensitivity, led to the development of molecular
      recognition imaging. By a combination of topographical imaging with force
      measurements, receptor sites are localized with nanometer accuracy. Topography
      and recognition of target molecules are thereby simultaneously mapped. Thus the
      AFM can identify specific components in a complex biological sample and retain
      its high resolution in imaging.

PMID- 16411738
TI  - Structure-function relationships of EcDOS, a heme-regulated phosphodiesterase
      from Escherichia coli.
AB  - Recent studies have revealed a new class of heme enzymes, the heme-based sensors,
      which are able to turn on or off cellular signal transduction pathways in
      response to environmental changes. One of these enzymes is the heme-regulated
      phosphodiesterase from Escherichia coli (EcDOS). This protein is composed of an N
      terminal heme-containing PAS domain and a C-terminal functional domain. PAS is an
      acronym formed from the names of the Drosophila period clock protein (PER),
      vertebrate aryl hydrocarbon receptor nuclear translocator (ARNT), and Drosophila
      single-minded protein (SIM). The heme cofactor in its PAS domain can act as a
      sensor of the cellular redox state that regulates the adenosine 3',5'-cyclic
      monophosphate (cAMP) phosphodiesterase activity. The crystal structures of its
      heme-containing PAS domain have helped clarify how the heme redox-dependent
      structural changes initiate intramolecular signal transduction. Here, we review
      recent findings on the structure-function relationships of EcDOS.

PMID- 16411739
TI  - Designer zinc finger proteins: tools for creating artificial DNA-binding
      functional proteins.
AB  - The design of artificial functional DNA-binding proteins has long been a goal for
      several research laboratories. The zinc finger proteins, which typically contain
      many fingers linked in tandem fashion, are some of the most studied DNA-binding
      proteins. The zinc finger protein's tandem arrangement and its the ability to
      recognize a wide variety of DNA sequences make it an attractive framework to
      design novel DNA-binding peptides/proteins. Our laboratory has utilized several
      design strategies to create novel zinc finger peptides by re-engineering the
      C(2)H(2)-type zinc finger motif of transcription factor Sp1. Some of the
      engineered zinc fingers have shown nuclease and catalytic functional properties.
      Based on these results, we present the design strategies for the creation of
      novel zinc fingers.

PMID- 16411740
TI  - Benefiting from the unique properties of lanthanide ions.
AB  - The recent upsurge of interest in contrast agents for magnetic resonance imaging,
      of luminescent chemosensors for medical diagnostic, and lately, for optical
      imaging of cells has generated an impressive momentum for the coordination and
      supramolecular chemistry of trivalent lanthanide ions. We shortly review the
      synthetic methods allowing the introduction of these spherical ions with
      fascinating optical and magnetic properties into elaborate mono- and polymetallic
      edifices. We then illustrate these methods by selected examples describing the
      use of (i) a coronand to produce luminescent liquid crystals, (ii) derivatized
      calixarenes for 4f-5f element separation, (iii) podates for the production of
      nanoparticles with high relaxivity and for sensitizing the near-infrared (NIR)
      emission, and (iv) self-assembly processes for producing functional bimetallic
      edifices.

PMID- 16411741
TI  - Chaperone holdase activity of human papillomavirus E7 oncoprotein.
AB  - E7 oncoprotein is the major transforming activity in human papillomavirus and
      shares sequence and functional properties with adenovirus E1A and SV40 T-antigen,
      in particular by targeting the pRb tumor suppressor. HPV 16 E7 forms spherical
      oligomers that display chaperone activity in thermal denaturation and chemical
      refolding assays of two model polypeptide substrates, citrate synthase and
      luciferase, and it does so at substoichiometric concentrations. We show that the
      E7 chaperone can stably bind model polypeptides and hold them in a state with
      significant tertiary structure, but does not bind the fully native proteins. The
      E7 oligomers bind native in vitro translated pRb without the requirement of it
      being unfolded, since the N-terminal domain of E7 containing the LXCXE binding
      motif is exposed. The N-terminal domain of E7 can interfere with pRb binding but
      not with the chaperone activity, which requires the C-terminal domain, as in most
      reported E7 activities. The ability to bind up to approximately 72 molecules of
      pRb by the oligomeric E7 form could be important either for sequestering pRb from
      Rb-E2F complexes or for targeting it for proteasome degradation. Thus, both the
      dimeric and oligomeric chaperone forms of E7 can bind Rb and various potential
      targets. We do not know at present if the chaperone activity of E7 plays an
      essential role in the viral life cycle; however, a chaperone activity may explain
      the large number of cellular targets reported for this oncoprotein.

PMID- 16411742
TI  - The DNA-binding domain of the ultraspiracle drives deformation of the response
      element whereas the DNA-binding domain of the ecdysone receptor is responsible
      for a slight additional change of the preformed structure.
AB  - Ecdysteroids control molting and metamorphosis in insects via a heterodimeric
      complex of two nuclear receptors, the ecdysone receptor (EcR) and ultraspiracle
      protein (Usp). We used fluorescence resonance energy transfer (FRET) to study the
      topology of the natural pseudopalindromic element from the hsp27 gene (hsp27pal)
      in complex with the DNA-binding domains of Usp and EcR (UspDBD and EcRDBD,
      respectively). Steady-state data revealed shortening of the end-to-end distance
      of the hsp27pal-derived probe. For the 70.8 +/- 0.6 A distance obtained for the
      UspDBD-complexed DNA a bend of about 23.1 +/- 2.9 degrees was measured. Nearly
      the same value (23.0 +/- 3.4 degrees) was obtained for the DNA complexed with the
      UspDBD/EcRDBD heterodimer. The respective bend angles estimated using
      fluorescence decay measurements were 19.0 +/- 2.1 degrees and 20.9 +/- 3.6
      degrees . Thus, the FRET data suggest for the first time that the UspDBD defines
      the architecture of the UspDBD/EcRDBD heterocomplex due to the significant
      deformation of the hsp27pal. This suggestion has been further reinforced using
      gel retardation experiments, which, in conjunction with high-resolution DNase I
      footprinting, indicate that the main contribution to the observed bend is given
      by the UspDBD itself, while binding of the EcRDBD molecule brings on a slight
      additional change of the preformed structure.

PMID- 16411743
TI  - Use of an in situ disulfide cross-linking strategy to study the dynamic
      properties of the cytoplasmic end of transmembrane domain VI of the M3 muscarinic
      acetylcholine receptor.
AB  - The ligand-induced activation of G protein-coupled receptors (GPCRs) is predicted
      to involve pronounced conformational changes on the intracellular surface or the
      receptor proteins. A reorientation of the cytoplasmic end of transmembrane domain
      VI (TM VI) is thought to play a key role in GPCR activation and productive
      receptor/G protein coupling. Disulfide cross-linking studies with solubilized,
      Cys-substituted mutant versions of bovine rhodopsin and the M3 muscarinic
      acetylcholine receptor suggested that the cytoplasmic end of TM VI is
      conformationally highly flexible, even in the absence of activating ligands
      (Farrens, D. L., et al. (1996) Science 274, 768-770; Zeng, F. Y., et al. (1999)
      J. Biol. Chem. 274, 16629-16640). To test the hypothesis that the promiscuous
      disulfide cross-linking pattern observed in these studies was caused by the use
      of solubilized receptor proteins endowed with increased conformational
      flexibility, we employed a recently developed in situ disulfide cross-linking
      strategy that allows the detection of disulfide bonds in Cys-substituted mutant
      M3 muscarinic receptors present in their native membrane environment.
      Specifically, we used membranes prepared from transfected COS-7 cells to analyze
      a series of double Cys mutant M3 receptors containing one Cys residue within the
      sequence K484(6.29) to S493(6.38) at the cytoplasmic end of TM VI and a second
      Cys residue at the cytoplasmic end of TM III (I169C(3.54)). This analysis
      revealed a disulfide cross-linking pattern that was strikingly more restricted
      than that observed previously with solubilized receptor proteins, both in the
      absence and in the presence of the muscarinic agonist, carbachol. Carbachol
      stimulated the formation of disulfide bonds in only two of the 10 analyzed mutant
      muscarinic receptors, I169C(3.54)/K484C(6.29) and I169C(3.54)/A488C(6.33),
      consistent with an agonist-induced rotation of the cytoplasmic end of TM VI.
      These findings underline the usefulness of analyzing the structural and dynamic
      properties of GPCRs in their native lipid environment.

PMID- 16411745
TI  - Molecular mode of action of a covalently inhibiting peptidomimetic on the human
      calpain protease core.
AB  - Calpain is a nearly ubiquitous Ca2+-activated proteolytic enzyme whose precise
      physiological function is unknown. However, aberrant Ca2+ homeostasis in the
      course of cellular injuries and certain diseases of the CNS appears to activate
      calpain, in turn promoting the degradation of key cytoskeletal and membrane
      proteins. Hyperactive calpain has also been implicated in various aging phenomena
      and diseases of late life. Therefore, calpain is considered a potential
      therapeutic target in preventing degenerations of many kinds. Despite its
      potential medicinal importance, known structural information about mu-calpain is
      limited to that from the rat enzyme. We have determined the crystal structure of
      the human mu-calpain protease core (hmuI-II) containing a Gly213Ala mutation and
      covalently inactivated by a peptidomimetic (ZLLYCH2F) at 2.0 A resolution. The
      methylene carbon of the inhibitor is bound to Cys115. Additional hydrogen bonding
      and hydrophobic interactions between active site residues and the inhibitor,
      including an intermolecular antiparallel beta-sheet arrangement
      characteristically observed with members of the papain family of cysteine
      proteinases, help to stabilize the complex and orient the inhibitor. The terminal
      ZL portion of the inhibitor is solvent-exposed and highly flexible, and is thus
      not involved in specific binding interactions with the enzyme. Two large enzyme
      regions flanking the active site are highly flexible; they may be important in
      recognition of calpain's natural protein substrates and in positioning them for
      catalysis. The implications for drug design are discussed.

PMID- 16411746
TI  - Light-induced reduction of bovine adrenodoxin via the covalently bound
      ruthenium(II) bipyridyl complex: intramolecular electron transfer and crystal
      structure.
AB  - Bovine adrenodoxin (Adx) plays an important role in the electron-transfer process
      in the mitochondrial steroid hydroxylase system of the bovine adrenal cortex.
      Using electron paramagnetic resonance (EPR) spectroscopy, we showed that
      photoreduction of the [2Fe-2S] cluster of Adx via (4'-methyl-2,2'
      bipyridine)bis(2,2'-bipyridine)ruthenium(II) [Ru(bpy)2(mbpy)] covalently attached
      to the protein surface can be used as a new approach to probe the "shuttle"
      hypothesis for the electron transfer by Adx. The 1.5 A resolution crystal
      structure of a 1:1 Ru(bpy)2(mbpy)-Adx(1-108) complex reveals the site of
      modification, Cys95, and allows to predict the possible intramolecular electron
      transfer pathways within the complex. Photoreduction of uncoupled Adx, mutant
      Adx(1-108), and Ru(bpy)2(mbpy)-Adx(1-108) using safranin T as the mediating
      electron donor suggests that two electrons are transferred from the dye to Adx.
      The intramolecular photoreduction rate constant for the ruthenated Adx has been
      determined and is discussed according to the predicted pathways.

PMID- 16411744
TI  - Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base
      variants on the geometry of phosphoryl transfer.
AB  - The hairpin ribozyme requires functional group contributions from G8 to assist in
      phosphodiester bond cleavage. Previously, replacement of G8 by a series of
      nucleobase variants showed little effect on interdomain docking, but a 3-250-fold
      effect on catalysis. To identify G8 features that contribute to catalysis within
      the hairpin ribozyme active site, structures for five base variants were
      determined by X-ray crystallography in a resolution range between 2.3 and 2.7 A.
      For comparison, a native all-RNA "G8" hairpin ribozyme structure was refined to
      2.05 A resolution. The native structure revealed a scissile bond angle (tau) of
      158 degrees, which is close to the requisite 180 degrees "in-line" geometry.
      Mutations G8(inosine), G8(diaminopurine), G8(aminopurine), G8(adenosine), and
      G8(uridine) folded properly, but exhibited nonideal scissile bond geometries (tau
      ranging from 118 degrees to 93 degrees) that paralleled their diminished solution
      activities. A superposition ensemble of all structures, including a previously
      described hairpin ribozyme-vanadate complex, indicated the scissile bond can
      adopt a variety of conformations resulting from perturbation of the chemical
      environment and provided a rationale for how the exocyclic amine of nucleobase 8
      promotes productive, in-line geometry. Changes at position 8 also caused
      variations in the A-1 sugar pucker. In this regard, variants A8 and U8 appeared
      to represent nonproductive ground states in which their 2'-OH groups mimicked the
      pro-R, nonbridging oxygen of the vanadate transition-state complex. Finally, the
      results indicated that ordered water molecules bind near the 2'-hydroxyl of A-1,
      lending support to the hypothesis that solvent may play an important role in the
      reaction.

PMID- 16411747
TI  - Chemical denaturation of the elongation factor 1alpha isolated from the
      hyperthermophilic archaeon Sulfolobus solfataricus.
AB  - The stability against chemical denaturants of the elongation factor EF-1alpha
      (SsEF-1alpha), a protein isolated from the hyperthermophilic archaeon Sulfolobus
      solfataricus has been characterized in detail. Indeed, the atypical shape of the
      protein structure and the unusual living conditions of the host organism prompted
      us to analyze the effect of urea and guanidine hydrochloride (GuHCl) on the GDP
      complex of the enzyme (SsEF-1alpha x GDP) by fluorescence and circular dichroism.
      These studies were also extended to the nucleotide-free form of the protein
      (nfSsEF-1alpha). Interestingly, the experiments show that the denaturation curves
      of both SsEF-1alpha forms present a single inflection point, which is indicative
      of a cooperative unfolding process with no intermediate species. Moreover, the
      chemically induced unfolding process of both SsEF-1alpha x GDP and nfSsEF-1alpha
      is fully reversible. Both SsEF-1alpha forms exhibit remarkable stability against
      urea, but they do not display a strong resistance to the denaturing action of
      GuHCl. These findings suggest that electrostatic interactions significantly
      contribute to SsEF-1alpha stability.

PMID- 16411748
TI  - Determinants of cooperativity and site selectivity in human ileal bile acid
      binding protein.
AB  - Human ileal bile acid binding protein (I-BABP) is a member of the family of
      intracellular lipid-binding proteins and is thought to play a role in the
      enterohepatic circulation of bile salts. Our group has previously shown that
      human I-BABP binds two molecules of glycocholate (GCA) with low intrinsic
      affinity but an extraordinary high degree of positive cooperativity. Besides the
      strong positive cooperativity, human I-BABP exhibits a high degree of site
      selectivity in its interactions with GCA and glycochenodeoxycholate (GCDA), the
      two major bile salts in humans. In this study, on the basis of our first
      generation nuclear magnetic resonance (NMR) structure of the ternary complex of
      human I-BABP with GCA and GCDA, we introduced single-residue mutations at certain
      key positions in the binding pocket that might disrupt a hydrogen-bonding
      network, a likely way of energetic communication between the two sites.
      Macroscopic binding parameters were determined using isothermal titration
      calorimetry, and site selectivity was monitored by NMR spectroscopy of
      isotopically enriched bile salts. According to our results, cooperativity and
      site selectivity are not linked in human I-BABP. While cooperativity is governed
      by a subtle interplay of entropic and enthalpic contributions, site selectivity
      appears to be determined by more localized enthalpic effects. Possible
      communication pathways between the two binding sites are discussed.

PMID- 16411749
TI  - Structure of calmodulin bound to a calcineurin peptide: a new way of making an
      old binding mode.
AB  - Calcineurin is a calmodulin-binding protein in brain and the only
      serine/threonine protein phosphatase under the control of Ca2+/calmodulin (CaM),
      which plays a critical role in coupling Ca2+ signals to cellular responses. CaM
      up-regulates the phosphatase activity of calcineurin by binding to the CaM
      binding domain (CBD) of calcineurin subunit A. Here, we report crystal structural
      studies of CaM bound to a CBD peptide. The chimeric protein containing CaM and
      the CBD peptide forms an intimate homodimer, in which CaM displays a native-like
      extended conformation and the CBD peptide shows alpha-helical structure.
      Unexpectedly, the N-terminal lobe from one CaM and the C-terminal lobe from the
      second molecule form a combined binding site to trap the peptide. Thus, the dimer
      provides two binding sites, each of which is reminiscent of the fully collapsed
      conformation of CaM commonly observed in complex with, for example, the myosin
      light chain kinase (MLCK) peptide. The interaction between the peptide and CaM is
      highly specific and similar to MLCK.

PMID- 16411750
TI  - Photolabeling of cardiolipin binding subunits within bovine heart cytochrome c
      oxidase.
AB  - Subunits located near the cardiolipin binding sites of bovine heart cytochrome c
      oxidase (CcO) were identified by photolabeling with arylazido-cardiolipin
      analogues and detecting labeled subunits by reversed-phase HPLC and HPLC
      electrospray ionization mass spectrometry. Two arylazido-containing cardiolipin
      analogues were synthesized: (1) 2-SAND-gly-CL with a nitrophenylazido group
      attached to the polar headgroup of cardiolipin (CL) via a linker containing a
      cleavable disulfide; (2) 2',2''-bis-(AzC12)-CL with two of the four fatty acid
      tails of cardiolipin replaced by 12-(N-4-azido-2-nitrophenyl) aminododecanoic
      acid. Both arylazido-CL derivatives were used to map the cardiolipin binding
      sites within two types of detergent-solubilized CcO: (1) intact 13-subunit CL
      containing CcO (three to four molecules of endogenous CL remain bound per CcO
      monomer); (2) 11-subunit CL-free CcO (subunits VIa and VIb are missing because
      they dissociate during CL removal). Upon the basis of these photolabeling
      studies, we conclude that (1) subunits VIIa, VIIc, and possibly VIII are located
      near the two high-affinity cardiolipin binding sites, which are present in either
      form of CcO, and (2) subunit VIa is located adjacent to the lower affinity
      cardiolipin binding site, which is only present in the 13-subunit form of CcO.
      These data are consistent with the recent CcO crystal structure in which one
      cardiolipin is located near subunit VIIa and a second is located near subunit VIa
      (PDB ID code referenced in Tomitake, T. et al. (2003) Proc. Natl. Acad. Sci.
      U.S.A. 100, 15304-15309). However, we propose that a third cardiolipin is bound
      between subunits VIIa and VIIc near the entrance to the D-channel. Cardiolipin
      bound at this location could potentially function as a proton antenna to
      facilitate proton entry into the D-channel. If true, it would explain the CcO
      requirement of bound cardiolipin for full electron transport activity.

PMID- 16411752
TI  - Metal-binding affinity of the transmembrane site in ZntA: implications for metal
      selectivity.
AB  - ZntA, a P1B-type ATPase, confers resistance specifically to Pb2+, Zn2+, and Cd2
      in Escherichia coli. Inductively coupled plasma mass spectrometry measurements
      show that ZntA binds two metal ions with high affinity, one in the N-terminal
      domain and another in the transmembrane domain. Both sites can bind monovalent
      and divalent metal ions. Two proteins, deltaN-ZntA, in which the N-terminal
      domain is deleted, and C59A/C62A-ZntA, in which the N-terminal metal-binding site
      is disabled by site-specific mutagenesis, can only bind one metal ion. Because
      C59A/C62A-ZntA can bind a metal ion at the transmembrane site, the N-terminal
      domain does not block direct access of metal ions to it from the cytosol. A third
      mutant protein, C392A/C394A-ZntA, in which cysteines from the conserved CPC motif
      in transmembrane helix 6 are altered, binds metal ions only at the N-terminal
      site, indicating that both these cysteines form part of the transmembrane site.
      The metal affinity of the transmembrane site was determined in deltaN-ZntA and
      C59A/C62A-ZntA by competition titration using a metal ion indicator and by
      tryptophan fluorescence quenching. The binding affinity for the physiological
      substrates, Zn2+, Pb2+, and Cd2+, as well as for the extremely poor substrates,
      Cu2+, Ni2+, and Co2+, range from 10(6)-10(10) M(-1), and does not correlate with
      the metal selectivity shown by ZntA. Selectivity in ZntA possibly results from
      differences in metal-binding geometry that produce different structural
      responses. The affinity of the transmembrane site for metal ions is of similar
      magnitude to that of the N-terminal site [Liu J. et al. (2005) Biochemistry 44,
      5159-5167]; thus, metal transfer between them would be facile.

PMID- 16411751
TI  - Human cytochrome b5 requires residues E48 and E49 to stimulate the 17,20-lyase
      activity of cytochrome P450c17.
AB  - Cytochrome P450c17 (CYP17) catalyzes both the 17alpha-hydroxylase and 17,20-lyase
      reactions in human steroid biosynthesis. Cytochrome b5 (b5) stimulates the rate
      of the 17,20-lyase reaction 10-fold with little influence on 17alpha-hydroxylase
      activity. Studies with apo-b5 suggest that stimulation of 17,20-lyase activity
      results from an allosteric action on the hCYP17 x POR complex, rather than
      electron transfer by b5. We hypothesized that specific residues on b5 interact
      with the hCYP17 x POR complex and that targeted mutation of surface-exposed
      residues might identify b5 residues critical for stimulating 17,20-lyase
      activity. We constructed, expressed, and purified 14 single plus 3 double b5
      mutations and assayed their ability to stimulate 17,20-lyase activity. Most
      mutations did not alter the capacity of b5 to stimulate 17,20-lyase activity or
      appeared to modestly alter the affinity of b5 for the hCYP17 x POR complex. In
      contrast, mutation of E48, E49, or R52 reduced the maximal stimulation of 17,20
      lyase activity. In particular, b5 mutation E48G + E49G lost over 95% of the
      capacity to stimulate 17,20-lyase activity, yet this mutation retained normal
      electron transfer properties. In addition, mutation E48G + E49G did not impair
      stimulation of 17,20-lyase activity by wild-type b5, suggesting that the mutation
      binds poorly to the site of the hCYP17 x POR complex occupied by b5. These data
      suggest that a specific allosteric binding site on b5, which includes residues
      E48, E49, and possibly R52, mediates the stimulation of 17,20-lyase activity.

PMID- 16411753
TI  - New insights into the mechanism of nucleoside hydrolases from the crystal
      structure of the Escherichia coli YbeK protein bound to the reaction product.
AB  - Nucleoside hydrolases (NHs) are enzymes that catalyze the excision of the N
      glycosidic bond in nucleosides to allow recycling of the nitrogenous bases. The
      fine details of the catalytic mechanism and the structural features imposing the
      substrate specificity of the various members of the NH family are still debated.
      Here we present the functional characterization of the Escherichia coli YbeK
      (RihA) protein as a pyrimidine nucleoside-preferring NH and its first crystal
      structure to 1.8 A resolution. The enzyme active site is occupied by either the
      alpha or beta anomer of ribose and provides the first structural description of
      the binding of the NH reaction product. While the amino acid residues involved in
      ribosyl binding are strictly conserved in pyrimidine-specific NHs, the residues
      involved in specific interactions with the nitrogenous bases differ considerably.
      Further comparison of the active site architecture of YbeK with the related NHs
      establishes structural determinants involved in triggering the conformational
      transition between the open and closed structures and suggests a mechanism for
      product release.

PMID- 16411754
TI  - Crystal structure of penicillin binding protein 4 (dacB) from Escherichia coli,
      both in the native form and covalently linked to various antibiotics.
AB  - The crystal structure of penicillin binding protein 4 (PBP4) from Escherichia
      coli, which has both DD-endopeptidase and DD-carboxypeptidase activity, is
      presented. PBP4 is one of 12 penicillin binding proteins in E. coli involved in
      the synthesis and maintenance of the cell wall. The model contains a penicillin
      binding domain similar to known structures, but includes a large insertion which
      folds into domains with unique folds. The structures of the protein covalently
      attached to five different antibiotics presented here show the active site
      residues are unmoved compared to the apoprotein, but nearby surface loops and
      helices are displaced in some cases. The altered geometry of conserved active
      site residues compared with those of other PBPs suggests a possible cause for the
      slow deacylation rate of PBP4.

PMID- 16411755
TI  - Fluoride inhibition of enolase: crystal structure and thermodynamics.
AB  - Enolase is a dimeric metal-activated metalloenzyme which uses two magnesium ions
      per subunit: the strongly bound conformational ion and the catalytic ion that
      binds to the enzyme-substrate complex inducing catalysis. The crystal structure
      of the human neuronal enolase-Mg2F2P(i) complex (enolase fluoride/phosphate
      inhibitory complex, EFPIC) determined at 1.36 A resolution shows that the
      combination of anions effectively mimics an intermediate state in catalysis. The
      phosphate ion binds in the same site as the phosphate group of the
      substrate/product, 2-phospho-D-glycerate/phosphoenolpyruvate, and induces binding
      of the catalytic Mg2+ ion. One fluoride ion bridges the structural and catalytic
      magnesium ions while the other interacts with the structural magnesium ion and
      the ammonio groups of Lys 342 and Lys 393. These fluoride ion positions
      correspond closely to the positions of the oxygen atoms of the substrate's
      carboxylate moiety. To relate structural changes resulting from fluoride,
      phosphate, and magnesium ions binding to those that are induced by phosphate and
      magnesium ions alone, we also determined the structure of the human neuronal
      enolase-Mg2P(i) complex (enolase phosphate inhibitory complex, EPIC) at 1.92 A
      resolution. It shows the closed conformation in one subunit and a mixture of open
      and semiclosed conformations in the other. The EPFIC dimer is essentially
      symmetric while the EPIC dimer is asymmetric. Isothermal titration calorimetry
      data confirmed binding of four fluoride ions per dimer and yielded Kb values of
      7.5 x 10(5) +/- 1.3 x 10(5), 1.2 x 10(5) +/- 0.2 x 10(5), 8.6 x 10(4) +/- 1.6 x
      10(4), and 1.6 x 10(4) +/- 0.7 x 10(4) M(-1). The different binding constants
      indicate negative cooperativity between the subunits; the asymmetry of EPIC
      supports such an interpretation.

PMID- 16411756
TI  - Origin and consequences of steric strain in the rhodopsin binding pocket.
AB  - To study the origin and the effects of steric strain on the chromophore
      conformation in rhodopsin, we have performed quantum-mechanical calculations on
      the wild-type retinal chromophore and four retinal derivatives, 13-demethyl-, 10
      methyl-13-demethyl-, 10-methyl-, and 9-demethylretinal. For the dynamics of the
      whole protein, a combined quantum mechanics/molecular mechanics method
      (DFTB/CHARMM) was used and for the calculation of excited-state properties the
      nonempirical CASSCF/CASPT2 method. After relaxation inside the protein, all
      chromophores show significant nonplanar distortions from C10 to C13, most
      strongly for 10-methylretinal and least pronounced for 9-demethylretinal. In all
      five cases, the dihedral angle of the C10-C11=C12-C13 bond is negative which
      attests to the strong chiral discrimination exerted by the protein pocket. The
      calculations show that the nonplanar distortion of the chromophore, including the
      sense of rotation, is caused by a combination of two effects: the fitting of both
      ends to the protein matrix which imposes a distance constraint and the bonding
      arrangement at the Schiff base terminus. With both the counterion Glu113 and
      Lys296 displaced off the plane of the chromophore, their binding to N16 exerts a
      torque on the chromophore. As a result, the polyene chain, from N16 to C13, is
      twisted in a clockwise manner against the remaining part of the chromophore,
      leading to a C11=C12 bond with the observed negative dihedral angle. Shifts of
      the absorption maxima are reproduced correctly, in particular, the red shift of
      the 10-methyl and the strong blue shift of the 9-demethyl analogue relative to
      the wild type. Calculated positive rotatory strengths of the alpha-CD bands are
      in agreement with the calculated absolute conformation of the mutant
      chromophores.

PMID- 16411757
TI  - The productive conformation of prostaglandin G2 at the peroxidase site of
      prostaglandin endoperoxide H synthase: docking, molecular dynamics, and site
      directed mutagenesis studies.
AB  - We present a plausible productive conformation obtained by docking calculations
      for the binding of prostaglandin G2 (PGG2) to the peroxidase site of
      prostaglandin endoperoxide H synthase-1 (PGHS-1, COX-1). The enzyme-substrate
      complex stability was verified by molecular dynamics. Structural analysis reveals
      the requirements for enzyme-substrate recognition and binding: the PGG2 15
      hydroperoxide group is in the proximity of the heme iron and participates in a
      hydrogen bond network with the conserved His207 and Gln203 and a water molecule,
      whereas the carboxylate group forms salt bridges with the remote Lys215 and
      Lys222. Site-directed mutagenesis showed that a single mutation of Lys215 or
      Lys222 does not affect enzyme activity, whereas dual mutation of these residues,
      to either alanine or glutamate, significantly decreases turnover. This indicates
      that the conserved cationic pocket is involved in enzyme-substrate binding.

PMID- 16411758
TI  - Evidence for redox cooperativity between c-type hemes of MauG which is likely
      coupled to oxygen activation during tryptophan tryptophylquinone biosynthesis.
AB  - MauG is a novel 42 kDa diheme protein which is required for the biosynthesis of
      tryptophan tryptophylquinone, the prosthetic group of methylamine dehydrogenase.
      The visible absorption and resonance Raman spectroscopic properties of each of
      the two c-type hemes and the overall redox properties of MauG are described. The
      absorption maxima for the Soret peaks of the oxidized and reduced hemes are 403
      and 418 nm for the low-spin heme and 389 and 427 nm for the high-spin heme,
      respectively. The resonance Raman spectrum of oxidized MauG exhibits a set of
      marker bands at 1503 and 1588 cm(-1) which exhibit frequencies similar to those
      of the nu3 and nu2 bands of c-type heme proteins with bis-histidine coordination.
      Another set of marker bands at 1478 and 1570 cm(-1) is characteristic of a high
      spin heme. Two distinct oxidation-reduction midpoint potential (E(m)) values of 
      159 and -244 mV are obtained from spectrochemical titration of MauG. However, the
      two nu3 bands located at 1478 and 1503 cm(-1) shift together to 1467 and 1492 cm(
      1), respectively, upon reduction, as do the Soret peaks of the low- and high-spin
      hemes in the absorption spectrum. Thus, the two hemes with distinct spectral
      properties are reduced and oxidized to approximately the same extent during redox
      titrations. This indicates that the high- and low-spin hemes have similar
      intrinsic E(m) values but exhibit negative redox cooperativity. After the first
      one-electron reduction of MauG, the electron equilibrates between hemes. This
      makes the second one-electron reduction of MauG more difficult. Thus, the two
      E(m) values do not describe redox properties of distinct hemes, but the first and
      second one-electron reductions of a diheme system with two equivalent hemes. The
      structural and mechanistic implications of these findings are discussed.

PMID- 16411759
TI  - Cation-specific structural accommodation within a catalytic RNA.
AB  - Metal ions facilitate the folding of the hairpin ribozyme but do not participate
      directly in catalysis. The metal complex cobalt(III) hexaammine supports folding
      and activity of the ribozyme and also mediates specific internucleotide
      photocrosslinks, several of which retain catalytic ability. These crosslinks
      imply that the active core structure organized by [Co(NH3)6]3+ is different from
      that organized by Mg2+ and that revealed in the crystal structure [Rupert, P. B.,
      and Ferre-D'Amare, A. R. (2001) Nature 410, 780-786] (1). Residues U+2 and C+3 of
      the substrate, in particular, adopt different conformations in [Co(NH3)6]3+. U+2
      is bulged out of loop A and stacked on residue G36, whereas the nucleotide at
      position +3 is stacked on G8, a nucleobase crucial for catalysis. Cleavage
      kinetics performed with +2 variants and a C+3 U variant correlate with the
      crosslinking observations. Variants that decreased cleavage rates in magnesium up
      to 70-fold showed only subtle decreases or even increases in observed rates when
      assayed in [Co(NH3)6]3+. Here, we propose a model of the [Co(NH3)6]3+-mediated
      catalytic core generated by MC-SYM that is consistent with these data.

PMID- 16411760
TI  - Identification and characterization of O-acetylpeptidoglycan esterase: a novel
      enzyme discovered in Neisseria gonorrhoeae.
AB  - Modification of the bacterial cell wall heteropolymer peptidoglycan by addition
      of an acetyl group to the C-6 hydroxyl group of N-acetylmuramoyl residues is
      known to inhibit the activity of muramidases (lysozymes) of innate immune
      systems. The O-acetylation of peptidoglycan also precludes the action of
      intrinsic lytic transglycosylases, enzymes that require a free C-6 hydroxyl group
      to generate their 1,6-anhydromuropeptide products. This class of autolysins is
      ubiquitous in peptidoglycan-synthesizing bacteria as they are responsible for
      insertion of pores and flagella, spore formation, and the general metabolism of
      peptidoglycan. We recently discovered a cluster of genes in the Neisseria
      gonorrhoeae chromosome that are proposed to participate in peptidoglycan O
      acetylation (Weadge, J. T., Pfeffer, J. M., and Clarke, A. J. (2005) BMC Microb.
      5, 49). In the current study, we demonstrate that one of these genes, ape1
      functions as an O-acetylpeptidoglycan esterase. The ape1 gene was cloned and
      overexpressed in Escherichia coli as a fusion protein with a hexa-histidine tag.
      The expressed protein was purified to apparent homogeneity and assayed for
      activity as an esterase using three different assays involving high-performance
      liquid chromatography and chromogenic detection methods which measured the
      release of ester-linked acetate from a variety of polymer and soluble substrates.
      These assays demonstrated that Ape1 has a higher specific activity on O
      acetylated peptidoglycan compared to O-acetylated xylan. Consequently, Ape1
      represents the first enzyme characterized as an O-acetylpeptidoglycan esterase.
      The physicochemical and kinetic parameters of Ape1 were determined using soluble
      chromogenic substrates for convenience. Thus, its pH optima for stability and
      activity were observed to be 6.0 and 6.2, respectively, while its optimum
      temperature for activity was 55 degrees C. Two forms of truncated Ape1 are
      generated in E. coli, one lacked the complete predicted N-terminal signal
      sequence, while the second involved a proteolytic cleavage within this signal
      sequence. The smaller truncated form was localized predominantly to the
      periplasm, whereas the larger form was mainly associated with the outer membrane,
      and to a lesser extent, the cytoplasmic membrane, sites expected for the
      maintenance of peptidoglycan.

PMID- 16411761
TI  - Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin
      formation.
AB  - The accumulation of the lipofuscin fluorophores in retinal pigment epithelial
      (RPE) cells leads to the blinding degeneration characteristic of Stargardt
      disease and related forms of macular degeneration. RPE lipofuscin, including the
      fluorophore A2E, forms in large part as a byproduct of the visual cycle.
      Inhibiting visual cycle function with small molecules is required to prevent the
      formation of the retinotoxic lipofuscins. This in turn requires identification of
      rate-limiting steps in the operation of the visual cycle. Specific, non-retinoid
      isoprenoid compounds are described here, and shown through in both in vitro and
      in vivo experiments, to serve as antagonists of RPE65, a protein that is
      essential for the operation of the visual cycle. These RPE65 antagonists block
      regeneration of 11-cis-retinal, the chromophore of rhodopsin, thereby
      demonstrating that RPE65 is at least partly rate-limiting in the visual cycle.
      Furthermore, chronic treatment of a mouse model of Stargardt disease with the
      RPE65 antagonists abolishes the formation of A2E. Thus, RPE65 is also on the rate
      limiting pathway to A2E formation. These nontoxic isoprenoid RPE65 antagonists
      are candidates for the treatment of forms of macular degeneration wherein
      lipofuscin accumulation is an important risk factor. These antagonists will also
      be used to probe the molecular function of RPE65 in vision.

PMID- 16411762
TI  - GTP-induced conformational changes in translin: a comparison between human and
      Drosophila proteins.
AB  - Human translin is a conserved protein, unique in its ability to bind both RNA and
      DNA. Interestingly, GTP binding has been implicated as a regulator of RNA/DNA
      binding function of mouse translin (TB-RBP). We cloned and overexpressed the
      translin orthologue from Drosophila melanogaster and compared its DNA/RNA binding
      properties in relation to GTP effects with that of human protein. Human translin
      exhibits a stable octameric state and binds ssDNA/RNA/dsDNA targets, all of which
      get attenuated when GTP is added. Conversely, Drosophila translin exhibits a
      stable dimeric state that assembles into a suboctameric (tetramer/hexamer) form
      and fails to bind ssDNA and RNA targets. Interestingly enough, CD spectral
      analyses, partial protease digestion profile revealed GTP-specific conformational
      changes in human translin, whereas the same were largely missing in Drosophila
      protein. Isothermal calorimetry delineated specific heat changes associated with
      GTP binding in human translin, which invoked subunit "loosening" in its octamers;
      the same effect was absent in Drosophila protein. We propose that GTP acts as a
      specific molecular "switch" that modulates the nucleic acid binding function
      selectively in human translin, perhaps by affecting its octameric configuration.

PMID- 16411763
TI  - Identification of the determinants for the specific recognition of single-strand
      telomeric DNA by Cdc13.
AB  - The single-strand overhang present at telomeres plays a critical role in
      mediating both the capping and telomerase regulation functions of telomeres. The
      telomere end-binding proteins, Cdc13 in Saccharomyces cerevisiae, Pot1 in higher
      eukaryotes, and TEBP in the ciliated protozoan Oxytricha nova, exhibit sequence
      specific binding to their respective single-strand overhangs. S. cerevisiae
      telomeres are composed of a heterogeneous mixture of GT-rich telomeric sequence,
      unlike in higher eukaryotes which have a simple repeat that is maintained with
      high fidelity. In yeast, the telomeric overhang is recognized by the essential
      protein Cdc13, which coordinates end-capping and telomerase activities at the
      telomere. The Cdc13 DNA-binding domain (Cdc13-DBD) binds these telomere sequences
      with high affinity (3 pM) and sequence specificity. To better understand the
      basis for this remarkable recognition, we have investigated the binding of the
      Cdc13-DBD to a series of altered DNA substrates. Although an 11-mer of GT-rich
      sequence is required for full binding affinity, only three of these 11 bases are
      recognized with high specificity. This specificity differs from that observed in
      the other known telomere end-binding proteins, but is well suited to the specific
      role of Cdc13 at yeast telomeres. These studies expand our understanding of
      telomere recognition by the Cdc13-DBD and of the unique molecular recognition
      properties of ssDNA binding.

PMID- 16411764
TI  - The N-terminal domain of human centrin 2 has a closed structure, binds calcium
      with a very low affinity, and plays a role in the protein self-assembly.
AB  - Centrins are well-conserved calcium binding proteins from the EF-hand superfamily
      implicated in various cellular functions, such as centrosome duplication, DNA
      repair, and nuclear mRNA export. The intrinsic molecular flexibility and the self
      association tendency make difficult the structural characterization of the
      integral protein. In this paper we report the solution structure, the Ca2+
      binding properties, and the intermolecular interactions of the N-terminal domain
      of two human centrin isoforms, HsCen1 and HsCen2. In the absence of Ca2+, the N
      terminal construct of HsCen2 revealed a compact core conformation including four
      almost antiparallel alpha-helices and a short antiparallel beta-sheet, very
      similar to the apo state structure of other calcium regulatory EF-hand domains.
      The first 25 residues show a highly irregular and dynamic structure. The three
      dimensional model for the N-terminal domain of HsCen1, based on the high sequence
      conservation and NMR spectroscopic data, shows very close structural properties.
      Ca2+ titration of the apo-N-terminal domain of HsCen1 and HsCen2, monitored by
      NMR spectroscopy, revealed a very weak affinity (10(2)-10(3) M(-1)), suggesting
      that the cellular role of this domain is not calcium dependent. Isothermal
      calorimetric titrations showed that an 18-residue peptide, derived from the N
      terminal unstructured fragment, has a significant affinity (approximately 10(5)
      M(-1)) for the isolated C-terminal domain, suggesting an active role in the self
      assembly of centrin molecules.

PMID- 16411766
TI  - Understanding the mechanism of the antimitogenic activity of suramin.
AB  - Fibroblast growth factors (FGFs) play crucial roles in the regulation of key
      cellular processes such as angiogenesis, differentiation, and tumor growth.
      Suramin, a polysulfonated naphthylurea, is known to be a potent inhibitor of FGF
      induced angiogenesis. Using isothermal titration calorimetry, we demonstrate that
      human acidic fibroblast growth factor (hFGF-1) binds to suramin with high
      affinity in the nanomolar range. The suramin:hFGF-1 binding stoichiometry is
      estimated to be 2:1. Size-exclusion chromatography data reveal that suramin
      oligomerizes hFGF-1 to form a stable tetramer. Thermal unfolding experiments
      monitored by steady state fluorescence, and limited trypsin digestion analysis
      data suggest that suramin-induced oligomerization of hFGF-1 occurs in two steps.
      The first step involves the binding of suramin at specific sites on the protein.
      Two molecules of suramin appear to bind simultaneously to one molecule of hFGF-1.
      Binding of suramin possibly involves formation of solvent-exposed nonpolar
      surfaces in hFGF-1. In the second step, FGF appears to oligomerize through
      coalescence of the solvent-accessible nonpolar surfaces. Results of the NMR
      experiments reveal that suramin binds to residues in the heparin binding pocket
      as well as to residues involved in FGF receptor binding. On the basis of the
      results of this study, we propose a model to explain the molecular mechanism(s)
      underlying the antimitogenic activity of suramin. To our knowledge, this is the
      first study in which suramin interaction sites on FGF have been characterized.

PMID- 16411765
TI  - DNA polymerase catalysis in the absence of Watson-Crick hydrogen bonds: analysis
      by single-turnover kinetics.
AB  - We report the first pre-steady-state kinetic studies of DNA replication in the
      absence of hydrogen bonds. We have used nonpolar nucleotide analogues that mimic
      the shape of a Watson-Crick base pair to investigate the kinetic consequences of
      a lack of hydrogen bonds in the polymerase reaction catalyzed by the Klenow
      fragment of DNA polymerase I from Escherichia coli. With a thymine isostere
      lacking hydrogen-bonding ability in the nascent pair, the efficiency (k(pol)/Kd)
      of the polymerase reaction is decreased by 30-fold, affecting the ground state
      (Kd) and transition state (k(pol)) approximately equally. When both thymine and
      adenine analogues in the nascent pair lack hydrogen-bonding ability, the
      efficiency of the polymerase reaction is decreased by about 1000-fold, with most
      of the decrease attributable to the transition state. Reactions using nonpolar
      analogues at the primer-terminal base pair demonstrated the requirement for a
      hydrogen bond between the polymerase and the minor groove of the primer-terminal
      base. The R668A mutation of Klenow fragment abolished this requirement,
      identifying R668 as the probable hydrogen-bond donor. Detailed examination of the
      kinetic data suggested that Klenow fragment has an extremely low tolerance of
      even minor deviations of the analogue base pairs from ideal Watson-Crick
      geometry. Consistent with this idea, some analogue pairings were better tolerated
      by Klenow fragment mutants having more spacious active sites. In contrast, the Y
      family polymerase Dbh was much less sensitive to changes in base pair dimensions
      and more dependent upon hydrogen bonding between base-paired partners.

PMID- 16411767
TI  - pKa of the mRNA cap-specific 2'-O-methyltransferase catalytic lysine by HSQC NMR
      detection of a two-carbon probe.
AB  - We have characterized the side chain pKa for a single lysine analogue within a
      316-residue protein containing 21 lysines and 1678 carbon atoms at natural
      isotope abundance. To do this, the single reactive cysteine of a K175C mutant of
      VP39 (the mRNA cap-specific 2'-O-methyltransferase from vaccinia virus) was
      modified to S-(beta-aminoethyl)cysteine (gamma-thialysine) using freshly prepared
      (13C)aziridine at room temperature. Modification was accompanied by the rescue of
      catalytic function at high specific activity. After the fastidious removal of the
      noncovalently protein-bound aziridine self-polymer using a novel chelating
      dialysis procedure, signals were monitored by HSQC NMR. Appropriately pH-shifting
      HSQC NMR peaks were identified in the (13C)aziridine-modified enzyme,
      corresponding to detection of the two covalently attached (13C)thioethylamino
      atoms. The identification was strengthened by comparison with the positions and
      pH shifts of spectral peaks for tripeptide controls, a small molecule aziridine
      self-polymer mimetic, and a cysteine-minus control enzyme. pH titration of the
      modified protein indicated an apparent pKa of 8.5, consistent with a perturbed
      pKa for the catalytic lysine and a model in which the surrounding charged groups
      direct the lysine epsilon-amino pKa via both local electrostatic environment and
      orbital directionality.

PMID- 16411768
TI  - Structure and dynamics of the HIV-1 Vpu transmembrane domain revealed by solid
      state NMR with magic-angle spinning.
AB  - We report solid-state nuclear magnetic resonance (NMR) measurements on the
      peptide Vpu(1-40), comprising residues 1-40 of the 81-residue type 1 integral
      membrane protein Vpu encoded by the HIV-1 genome. On the basis of a combination
      of 13C and 15N NMR chemical shifts under magic-angle spinning (MAS), effects of
      local mobility on NMR signal intensities, site-specific MAS NMR line widths, and
      NMR-detected hydrogen-deuterium exchange, we develop a model for the structure
      and dynamics of the Vpu(1-40) monomer in phospholipid bilayer membranes. Our data
      are largely consistent with earlier structural studies of Vpu peptides by Opella
      and co-workers, in which solution NMR and solid-state NMR without MAS were used,
      but our data provide new information about local variations in the degree of
      mobility and structural order. In addition, our data indicate that the
      transmembrane alpha-helix of Vpu(1-40) extends beyond the hydrophobic core of the
      bilayer. We find no evidence for heterogeneity in the conformation and
      intermolecular contacts of the transmembrane alpha-helix, with the exception of
      two distinct chemical shifts observed for the C alpha and C beta atoms of A18
      that may reflect distinct modes of helix-helix interaction. These results have
      possible implications for the supramolecular structure of Vpu oligomers that form
      cation-selective ion channels.

PMID- 16411769
TI  - A novel calcium-independent peripheral membrane-bound form of annexin B12.
AB  - Annexins are soluble proteins that can interact with membranes in a Ca2+
      dependent manner. Recent studies have shown that they can also undergo Ca2+
      independent membrane interactions that are modulated by pH and phospholipid
      composition. Here, we investigated the structural changes that occurred during
      Ca2+-independent interaction of annexin B12 with phospholipid vesicles as a
      function of pH. Electron paramagnetic resonance analysis of a helical hairpin
      encompassing the D and E helices in the second repeat of the protein showed that
      this region refolded and formed a continuous amphipathic alpha helix following
      Ca2+-independent binding to membranes at mildly acidic pH. At pH 4.0, this helix
      assumed a transmembrane topography, but at pH approximately 5.0-5.5, it was
      peripheral and approximately parallel to the membrane. The peripheral form was
      reversibly converted into the transmembrane form by lowering the pH and vice
      versa. Furthermore, analysis of vesicles incubated with annexin B12 using freeze
      fracture electron microscopy methods showed classical intramembrane particles at
      pH 4.0 but none at pH 5.3. Together, these data raise the possibility that the
      peripheral-bound form of annexin B12 could act as a kinetic intermediate in the
      formation of the transmembrane form of the protein.

PMID- 16411770
TI  - Membrane topology of human ASBT (SLC10A2) determined by dual label epitope
      insertion scanning mutagenesis. New evidence for seven transmembrane domains.
AB  - The membrane topology of the human apical sodium-dependent bile acid transporter
      (hASBT) remains unresolved. Whereas N-glycosylation analysis favors a 7
      transmembrane (TM) model, membrane insertion scanning supports a 9TM topology. In
      order to resolve this controversy, we used dual label epitope insertion to
      systematically examine the topological framework of hASBT. Two distinct epitopes,
      hemagglutinin (HA) and FLAG, were individually inserted by inverted PCR
      mutagenesis at strategic positions along the hASBT sequence. Cell surface
      biotinylation and immunoblotting with epitope-specific and anti-hASBT antibodies
      confirmed expression and trafficking of the mutants to the plasma membrane.
      Confocal microscopy confirmed membrane localization of epitope-tagged hASBT in
      saponin-treated (permeabilized) and nonpermeabilized transfected COS-1 and MDCK
      cells. Tags at positions 116, 120, 186, 270, and 284 were accessible to the
      epitope antibodies in nonpermeabilized cells, indicative of the extracellular
      localization of loops 1 (99-130), 2 (180-191), and 3 (253-287). The corresponding
      positions in the 9TM model were predicted to be intracellular or membrane bound.
      Epitope mutants at residues 56, 92, 156, and 221 were only detected after
      treatment with saponin, indicating the intracellular localizations of loops 1 (50
      73), 2 (150-160), 3 (215-227) as predicted by a 7TM model. Our results also
      confirm the exofacial and cytosolic localization of N- and C-terminal tails,
      respectively. With the exception of constructs inserted at position 120, epitope
      mutants displayed active, sodium-dependent taurocholate uptake. Consequently, our
      study strongly supports a 7TM topology for hASBT and refutes the previously
      proposed 9TM model.

PMID- 16411771
TI  - Structural characterization of Na,K-ATPase from shark rectal glands by extensive
      trypsinization.
AB  - Extensive trypsinization of Na,K-ATPase from the salt gland of Squalus acanthias
      removes about half of the extramembranous protein mass of the alpha-subunit,
      while leaving the beta-subunit intact. Sequence analysis and epitope recognition
      of the remaining alpha-peptides show that transmembrane segments M1/M2 and M3/M4
      are present when trypsinization is performed in either NaCl or RbCl. The M5/M6
      segment and the intact 19-kDa peptide (M7-M10) are detected in Rb-trypsinized
      membranes but not in Na-trypsinized membranes. The L7/L8 loop is associated with
      Na-trypsinized membranes, indicating the presence of an M7/M8 or M8/M9 fragment.
      Freeze-fracture electron microscopy of both Rb- and Na-trypsinized membranes
      reveals intramembranous particles that indicate a retained cluster of peptides,
      even in the absence of an intact 19-kDa fragment. The rotational diffusion of
      covalently spin-labeled trypsinized complexes is studied in the presence of
      poly(ethylene glycol) or glycerol by using saturation transfer electron spin
      resonance. Rotational correlation times in aqueous poly(ethylene glycol) are
      longer than in glycerol solutions of the same viscosity and increase nonlinearly
      with the viscosity of the suspending medium, indicating that poly(ethylene
      glycol) induces aggregation of the tryptic peptides (and beta-subunit) within the
      membrane. The aggregates of enzyme trypsinized in the presence of NaCl are larger
      than those for enzyme trypsinized in RbCl, at both low and high aqueous
      viscosities. Similarities in mobility for native and Rb-trypsinized enzymes
      suggest either a change in average orientation of the spin-label upon
      trypsinization or that trypsinization leads to a reorganized protein structure
      that is more prone to aggregation.

PMID- 16411772
TI  - Kinetic and crystallographic analysis of mutant Escherichia coli aminopeptidase
      P: insights into substrate recognition and the mechanism of catalysis.
AB  - Aminopeptidase P (APPro) is a manganese-dependent enzyme that cleaves the N
      terminal amino acid from polypeptides where the second residue is proline. APPro
      shares a similar fold, substrate specificity, and catalytic mechanism with
      methionine aminopeptidase and prolidase. To investigate the roles of conserved
      residues at the active site, seven mutant forms of APPro were characterized
      kinetically and structurally. Mutation of individual metal ligands selectively
      abolished binding of either or both Mn(II) atoms at the active site, and none of
      these metal-ligand mutants had detectable catalytic activity. Mutation of the
      conserved active site residues His243 and His361 revealed that both are required
      for catalysis. We propose that His243 stabilizes substrate binding through an
      interaction with the carbonyl oxygen of the requisite proline residue of a
      substrate and that His361 stabilizes substrate binding and the gem-diol catalytic
      intermediate. Sequence, structural, and kinetic analyses reveal that His350,
      conserved in APPro and prolidase but not in methionine aminopeptidase, forms part
      of a hydrophobic binding pocket that gives APPro its proline specificity.
      Further, peptides in which the required proline residue is replaced by N
      methylalanine or alanine are cleaved by APPro, but they are extremely poor
      substrates due to a loss of interactions between the prolidyl ring of the
      substrate and the hydrophobic proline-binding pocket.

PMID- 16411773
TI  - Cholesterol interacts with transmembrane alpha-helices M1, M3, and M4 of the
      Torpedo nicotinic acetylcholine receptor: photolabeling studies using
      [3H]Azicholesterol.
AB  - The photoactivatable sterol probe [3alpha-(3)H]6-Azi-5alpha-cholestan-3beta-ol
      ([3H]Azicholesterol) was used to identify domains in the Torpedo californica
      nicotinic acetylcholine receptor (nAChR) that interact with cholesterol.
      [3H]Azicholesterol partitioned into nAChR-enriched membranes very efficiently
      (>98%), photoincorporated into nAChR subunits on an equal molar basis, and
      neither the pattern nor the extent of labeling was affected by the presence of
      the agonist carbamylcholine, consistent with photoincorporation at the nAChR
      lipid-protein interface. Sites of [3H]Azicholesterol incorporation in each nAChR
      subunit were initially mapped by Staphylococcus aureus V8 protease digestion to
      two relatively large homologous fragments that contain either the transmembrane
      segments M1-M2-M3 (e.g., alphaV8-20) or M4 (e.g., alphaV8-10). The distribution
      of [3H]Azicholesterol labeling between these two fragments (e.g., alphaV8-20,
      29%; alphaV8-10, 71%), suggests that the M4 segment has the greatest interaction
      with membrane cholesterol. Photolabeled amino acid residues in each M4 segment
      were identified by Edman degradation of isolated tryptic fragments and generally
      correspond to acidic residues located at either end of each transmembrane helix
      (e.g., alphaAsp-407). [3H]Azicholesterol labeling was also mapped to peptides
      that contain either the M3 or M1 segment of each nAChR subunit. These results
      establish that cholesterol likely interacts with the M4, M3, and M1 segments of
      each subunit, and therefore, the cholesterol binding domain fully overlaps the
      lipid-protein interface of the nAChR.

PMID- 16411775
TI  - How gastric lipase, an interfacial enzyme with a Ser-His-Asp catalytic triad,
      acts optimally at acidic pH.
AB  - Gastric lipase is active under acidic conditions and shows optimum activity on
      insoluble triglycerides at pH 4. The present results show that gastric lipase
      also acts in solution on vinyl butyrate, with an optimum activity above pH 7,
      which suggests that gastric lipase is able to hydrolyze ester bonds via the
      classical mechanism of serine hydrolases. These results support previous
      structural studies in which the catalytic triad of gastric lipase was reported to
      show no specific features. The optimum activity of gastric lipase shifted toward
      lower pH values, however, when the vinyl butyrate concentration was greater than
      the solubility limit. Experiments performed with long-chain triglycerides showed
      that gastric lipase binds optimally to the oil-water interface at low pH values.
      To study the effects of the pH on the adsorption step independently from
      substrate hydrolysis, gastric lipase adsorption on solid hydrophobic surfaces was
      monitored by total internal reflection fluorescence (TIRF), as well as using a
      quartz crystal microbalance. Both techniques showed a pH-dependent reversible
      gastric lipase adsorption process, which was optimum at pH 5 (Kd = 6.5 nM).
      Lipase adsorption and desorption constants (ka = 147,860 M(-1) s(-1) and kd = 139
      x 10(-4) s(-1) at pH 6) were estimated from TIRF experiments. These results
      indicate that the optimum activity of gastric lipase at acidic pH is only
      "apparent" and results from the fact that lipase adsorption at lipid-water
      interfaces is the pH-dependent limiting step in the overall process of insoluble
      substrate hydrolysis. This specific kinetic feature of interfacial enzymology
      should be taken into account when studying any soluble enzyme acting on an
      insoluble substrate.

PMID- 16411774
TI  - Stepwise deamidation of ribonuclease A at five sites determined by top down mass
      spectrometry.
AB  - Although deamidation at asparagine and glutamine has been found in numerous
      studies of a variety of proteins, in almost all cases the analytical methodology
      that was used could detect only a single site of deamidation. For the extensively
      studied case of reduced bovine ribonuclease A (13,689 Da), only Asn67 deamidation
      has been demonstrated previously, although one study found three monodeamidated
      fractions. Here top down tandem mass spectrometry shows that Asn67 deamidation is
      extensive before Asn71 and Asn94 react; these are more than half deamidated
      before Asn34 reacts, and its deamidation is extensive before that at Gln74 is
      initiated. Except for the initial Asn67 site, these large reactivity differences
      correlate poorly with neighboring amino acid identities and instead indicate
      residual conformational effects despite the strongly denaturing media that were
      used; deamidation at Asn67 could enhance that at Asn71, and these enhance that at
      Gln74. This success in the site-specific quantitation of deamidation in a 14 kDa
      protein mixture, despite the minimal 1 Da (-NH2 --> -OH) change in the molecular
      mass, is further evidence of the broad applicability of the top down MS/MS
      methodology for characterization of protein posttranslational modifications.

PMID- 16411776
TI  - Electron paramagnetic resonance studies of the iron-sulfur centers from complex I
      of Rhodothermus marinus.
AB  - Rhodothermus marinus, a thermohalophilic gram negative bacterium, contains a type
      I NADH/quinone oxidoreductase (complex I). Its purification was optimized,
      yielding large amounts of pure and active protein. Furthermore, the stoichiometry
      of NADH oxidation and quinone reduction was shown to be 1:1. The large amounts of
      protein enabled a thorough characterization by electron paramagnetic resonance
      (EPR) spectroscopy at different temperatures and microwave powers, using NADH,
      NADPH, and dithionite as reducing agents. A minimum of two [2Fe-2S](2+/1+) and
      four [4Fe-4S](2+/1+) centers were observed in the purified complex. Redox
      titrations monitored by EPR spectroscopy made possible the determination of the
      reduction potentials of the iron-sulfur centers; with the exception of one of the
      [4Fe-4S](2+/1+) centers, which has a lower reduction potential, all the other
      centers have reduction potentials of -240 +/- 20 mV, pH 7.5.

PMID- 16411777
TI  - Kinetic and spectroscopic studies on the quercetin 2,3-dioxygenase from Bacillus
      subtilis.
AB  - Quercetin 2,3-dioxygenase from Bacillus subtilis (QueD) converts the flavonol
      quercetin and molecular oxygen to 2-protocatechuoylphloroglucinolcarboxylic acid
      and carbon monoxide. QueD, the only known quercetin 2,3-dioxygenase from a
      prokaryotic organism, has been described as an Fe2+-dependent bicupin
      dioxygenase. Metal-substituted QueDs were generated by expressing the enzyme in
      Escherichia coli grown on minimal media in the presence of a number of divalent
      metals. The addition of Mn2+, Co2+, and Cu2+ generated active enzymes, but the
      addition of Zn2+, Fe2+, and Cd2+ did not increase quercetinase activity to any
      significant level over a control in which no divalent ions were added to the
      media. The Mn2+- and Co2+-containing QueDs were purified, characterized by metal
      analysis and EPR spectroscopy, and studied by steady-state kinetics. Mn2+ was
      found to be incorporated nearly stoichiometrically to the two cupin motifs. The
      hyperfine coupling constant of the g = 2 signal in the EPR spectra of the Mn2+
      containing enzyme showed that the two Mn2+ ions are ligated in an octahedral
      coordination. The turnover number of this enzyme was found to be in the order of
      25 s(-1), nearly 40-fold higher than that of the Fe2+-containing enzyme and
      similar in magnitude to that of the Cu2+-containing quercertin 2,3-dioxygenase
      from Aspergillus japonicus. In addition, kinetic and spectroscopic data suggest
      that the catalytic mechanism of QueD is different from that of the Aspergillus
      quercetinases but similar to that proposed for the extradiol catechol
      dioxygenases. This study provides evidence that Mn2+ might be the preferred
      cofactor for this enzyme and identifies QueD as a new member of the manganese
      dioxygenase family.

PMID- 16411778
TI  - Exchange of glutamine-217 to glutamate of Clostridium limosum exoenzyme C3 turns
      the asparagine-specific ADP-ribosyltransferase into an arginine-modifying enzyme.
AB  - C3-like ADP-ribosyltransferaseses are produced by Clostridium species, Bacillus
      cereus, and various Staphylococcus aureus strains. The exoenzymes modify the low
      molecular-mass GTPases RhoA, B, and C. In structural studies of C3-like
      exoenzymes, an ARTT-motif (ADP-ribosylating turn-turn motif) was identified that
      appears to be involved in substrate specificity and recognition (Han, S., Arvai,
      A. S., Clancy, S. B., Tainer, J. A. (2001) J. Mol. Biol. 305, 95-107). Exchange
      of Gln217, which is a key residue of the ARTT-motif, to Glu in C3 from
      Clostridium limosum results in inhibition of ADP-ribosyltransferase activity
      toward RhoA. The mutant protein is still capable of NAD-binding and possesses
      NAD+ glycohydrolase activity. Whereas recombinant wild-type C3 modifies Rho
      proteins specifically at an asparagine residue (Asn41), Gln217Glu-C3 is capable
      of ADP-ribosylation of poly-arginine but not poly-asparagine. Soybean trypsin
      inhibitor, a model substrate for many arginine-specific ADP-ribosyltransferases,
      is modified by the Gln217Glu-C3 transferase. Also in C3 ADP-ribosyltransferases
      from Clostridium botulinum and B. cereus, the exchange of the equivalent Gln
      residue to Glu blocked asparagine modification of RhoA but elicited arginine
      specific ADP-ribosylation. Moreover, the Gln217Glu-C3lim transferase was able to
      ADP-ribosylate recombinant wild-type C3lim at Arg86, resulting in decrease in ADP
      ribosyltransferase activity of the wild-type enzyme. The data indicate that the
      exchange of one amino acid residue in the ARTT-motif turns the asparagine
      modifying ADP-ribosyltransferases of the C3 family into arginine-ADP-ribosylating
      transferases.

PMID- 16411779
TI  - Structure and stability of hereditary spherocytosis mutants of the cytosolic
      domain of the erythrocyte anion exchanger 1 protein.
AB  - Anion exchanger 1 (AE1, Band 3) is the predominant membrane protein of
      erythrocytes. Its 52 kDa C-terminal domain functions as a chloride-bicarbonate
      exchanger, while its 43 kDa N-terminal cytosolic domain (cdb3) anchors the
      cytoskeleton to the membrane. Several proteins bind to cdb3, including protein
      4.2, a cytoskeletal protein. Three mutations in cdb3 are associated with
      hereditary spherocytosis (HS) and decreased levels of protein 4.2 in
      erythrocytes. In this study, these cdb3 mutants (E40K, G130R, and P327R) were
      expressed in and purified from Escherichia coli. Sedimentation experiments showed
      that the wild-type and mutant proteins are dimers. No difference in secondary
      structure between mutant and wild-type proteins was detected using circular
      dichroism (CD) analysis. The wild-type and mutant proteins underwent similar pH
      dependent conformational changes when monitored by intrinsic tryptophan
      fluorescence. Urea denaturation of proteins monitored by intrinsic fluorescence
      showed no significant differences in the sensitivity of the proteins to this
      chemical denaturant. Thermal denaturation monitored by CD and by calorimetry
      revealed that only the P327R mutant had a significantly lower midpoint of
      transition (approximately 5 degrees C) than the wild-type protein, suggesting a
      modest decrease in stability. The results show that the HS mutant cdb3 proteins
      do not differ to any great extent in structure from the wild-type protein,
      suggesting that the HS mutations may directly affect protein 4.2 binding.

PMID- 16411780
TI  - Sumoylation of the yeast Gcn5 protein.
AB  - Sumoylation, the process by which the ubiquitin-related SUMO protein is
      covalently attached to lysine side chains in other proteins, is involved in
      numerous processes in the eukaryotic cell, including transcriptional repression.
      In this study, we identify Gcn5, the histone-modifying subunit of the
      transcriptional regulatory complex SAGA, as a sumoylation substrate in yeast. In
      vitro, multiple sumoylation of recombinant Gcn5 alone or as a trimer with its
      interacting proteins Ada2 and Ada3 did not affect Gcn5's histone
      acetyltransferase (HAT) activity, suggesting that modification of Gcn5 with yeast
      SUMO (Smt3) may not directly regulate its HAT function. Through site-directed
      mutagenesis, the primary in vivo sumoylation site was identified as lysine-25,
      although an unsumoylatable K-to-R mutation of this residue led to no obvious in
      vivo effects. However, fusion of SUMO to the N-terminus of Gcn5 to mimic
      constitutive sumoylation resulted in defective growth on 3-aminotriazole media
      and reduced basal and activated transcription of the SAGA-dependent gene TRP3.
      Taken together with recent identification of multiple additional subunits of SAGA
      as sumoylated proteins in vivo, these data suggest that Gcn5 sumoylation may have
      an inhibitory role in transcriptional regulation.

PMID- 16411781
TI  - Relaxin-3: improved synthesis strategy and demonstration of its high-affinity
      interaction with the relaxin receptor LGR7 both in vitro and in vivo.
AB  - Relaxin-3 is a member of the human relaxin peptide family, the gene for which,
      RLN3, is predominantly expressed in the brain. Mapping studies in the rodent
      indicate a highly developed network of RLN3, RLN1, and relaxin receptor
      expressing cells in the brain, suggesting that relaxin peptides have important
      functional roles in the central nervous system. A regioselective disulfide-bond
      synthesis protocol was developed and used for the chemical synthesis of human
      (H3) relaxin-3. The selectively S-protected A and B chains were combined by
      stepwise formation of each of the three insulin-like disulfides via aeration,
      thioloysis, and iodolysis. Judicious positioning of the three sets of S
      protecting groups was crucial for acquisition of synthetic H3 relaxin in a good
      overall yield. The activity of the peptide was tested against relaxin family
      peptide receptors. Although the highest activity was demonstrated on the human
      relaxin-3 receptor (GPCR135), the peptide also showed high activity on relaxin
      receptors (LGR7) from various species and variable activity on the INSL3 receptor
      (LGR8). Recombinant mouse prorelaxin-3 demonstrated similar activity to H3
      relaxin, suggesting that the presence of the C peptide did not influence the
      conformation of the active site. H3 relaxin was also able to activate native LGR7
      receptors. It stimulated increased MMP-2 expression in LGR7-expressing rat
      ventricular fibroblasts in a dose-dependent manner and, following infusion into
      the lateral ventricle of the brain, stimulated water drinking in rats, activating
      LGR7 receptors located in the subfornical organ. Thus, H3 relaxin is able to
      interact with the relaxin receptor LGR7 both in vitro and in vivo.

PMID- 16411782
TI  - A laser flash-induced kinetic analysis of in vivo photosystem I reduction by site
      directed mutants of plastocyanin and cytochrome c6 in Synechocystis sp. PCC 6803.
AB  - In cyanobacteria, plastocyanin and cytochrome c6 are two soluble metalloproteins
      which can alternately serve as electron donors to photosystem I. From site
      directed mutagenesis studies in vitro, it is well-established that both
      hydrophobic and electrostatic forces are involved in the interaction between the
      donor proteins and photosystem I. Hence, two isofunctional areas, a hydrophobic
      one in the north and an acidic one in the east, have been described on the
      surface of both electron donors. In this work, we have tested the relevance of
      such kinds of interactions in the photosystem I reduction inside the cell.
      Several plastocyanin and cytochrome c6 site-directed mutant strains affecting
      both the acidic and hydrophobic regions of the two metalloproteins, which were
      previously characterized in vitro, have been constructed. The photosystem I
      reduction kinetics of the different mutants have been analyzed by laser flash
      absorption spectroscopy. Relevant differences have been found between the in
      vitro and in vivo results, mainly regarding the role played by the electrostatic
      interactions. Adding positive electrostatic charges to the acidic patch of
      plastocyanin and cytochrome c6 promotes an enhanced interaction with photosystem
      I in vitro but yields the opposite effect in vivo. These discrepancies are
      discussed in view of the different environmental conditions, in vitro and in
      vivo, for the reaction mechanism of photosystem I reduction, namely, differential
      interaction of the electron donors with the thylakoidal membrane and kinetics of
      donor exchange.

PMID- 16411785
TI  - A pilot study: the effects of music therapy interventions on middle school
      students' ESL skills.
AB  - The purpose of this study was to investigate the effects of music therapy
      techniques on the story retelling and speaking skills of English as a Second
      Language (ESL) middle school students. Thirty-four middle school students of
      Hispanic heritage, ages 10-12, in high and low-functioning groups participated in
      the study for 12 weeks. Pretest to posttest data yielded significant differences
      on the story retelling skills between the experimental and control groups. Chi
      Square comparisons on English speaking skills also yielded significant results
      over 3 months of music therapy intervention. A variety of music therapy
      techniques were used including music and movement, active music listening, group
      chanting and singing, musical games, rhythmic training, music and sign language,
      and lyric analysis and rewrite activities as supplemental activities to the ESL
      goals and objectives. Comparisons of individual subjects' scores indicated that
      all of the students in the experimental groups scored higher than the control
      groups on story retelling skills (with the exception of 1 pair of identical
      scores), regardless of high and low functioning placement. Monthly comparisons of
      the high and low functioning experimental groups indicated significant
      improvements in English speaking skills as well.

PMID- 16411786
TI  - A descriptive study of private practice in music therapy.
AB  - Of professional music therapists in the American Music Therapy Association, 9%
      report being self-employed or in private practice. The purpose of this paper was
      to provide initial data concerning music therapists who are in private practice.
      The researchers successfully sent out 353 surveys and 118 were completed and
      returned via electronic mail for a response rate of 33.4%. Although general,
      results indicate that music therapists in private practice are active within the
      profession, doing presentations and inservices, conducting research, supervising
      practica students and interns, and keeping current with forthcoming research.
      Data indicate that most music therapists chose private practice due to a more
      flexible schedule, increased salary, and the lack of previously established job
      opportunities. Additionally, 65.8% of respondents reported having a bachelor's
      degree in music therapy, 29.2% reported having a master's degree, and 5.1 %
      reported having a doctoral degree. Quantitative results, rationale, and
      suggestions are included in an attempt to assist music therapists who are
      interested in starting private practices.

PMID- 16411783
TI  - A bromoenol lactone suicide substrate inactivates group VIA phospholipase A2 by
      generating a diffusible bromomethyl keto acid that alkylates cysteine thiols.
AB  - Phospholipases A2 (PLA2) comprise a superfamily of enzymes that hydrolyze
      phospholipids to a free fatty acid, e.g., arachidonate, and a 2-lysophospholipid.
      Dissecting their individual functions has relied in large part on pharmacological
      inhibitors that discriminate among PLA2. Group VIA PLA2 (iPLA2beta) has a GTSTG
      serine lipase consensus sequence, and studies with a bromoenol lactone (BEL)
      suicide substrate inhibitor have been taken to suggest that iPLA2beta
      participates in a wide variety of biological processes. Such conclusions presume
      inhibitor specificity. Inhibition by BEL requires its hydrolysis by and results
      in uncharacterized covalent modification(s) of iPLA2beta. We performed mass
      spectrometric analyses of proteolytic digests of BEL-treated iPLA2beta to
      identify modifications associated with loss of activity. The GTSTG active site
      and large flanking regions of sequence are not modified by BEL treatment, but
      most iPLA2beta Cys residues are alkylated at various BEL concentrations to form a
      thioether linkage to a BEL keto acid hydrolysis product. Synthetic Cys-containing
      peptides are alkylated when incubated with iPLA2beta and BEL, which reflects
      iPLA2beta-catalyzed BEL hydrolysis to a diffusible bromomethyl keto acid product
      that reacts with distant thiols. The BEL concentration dependence of Cys651
      alkylation closely parallels that of loss of iPLA2beta activity. No amino acid
      residues other than Cys were found to be modified, suggesting that Cys alkylation
      is the covalent modification of iPLA2beta responsible for loss of activity, and
      the alkylating species appears to be a diffusible hydrolysis product of BEL
      rather than a tethered acyl-enzyme intermediate.

PMID- 16411787
TI  - Juliette Alvin: her legacy for music therapy in Japan.
AB  - This historical study explored the contributions of Juliette Alvin to the early
      development of Japanese music therapy. Alvin visited Japan twice, once in 1967
      and once in 1969. Despite the brevity of her stays, Alvin presented Japanese
      music therapy pioneers with a vivid picture of music therapy profession and
      clinical practice. Professional associations were launched, catalyzed by her
      visit. Alvin's clinical demonstrations inspired one of the music therapy pioneers
      to explore not only his own philosophy but a comprehensive view of the future
      direction of Japanese music therapy. A young musician, who worked as an assistant
      in Alvin's sessions, adopted her approach and became a leader in Japanese music
      therapy. Information about Alvin were obtained from letters, books, newspapers,
      journal articles, interviews with Japanese music therapy pioneers, and Alvin's
      own reports on her practice in Japan. Implications of Alvin's approach are also
      discussed for the role that music therapy today can play in addressing the needs
      of clients.

PMID- 16411788
TI  - Testing a model of domain learning in music therapy.
AB  - This study is a measure of the effectiveness of music therapy education by
      testing it against a proven educational model. It evaluates the role of
      knowledge, interest and learning strategies in the Model of Domain Learning
      (Alexander, 1997, 2003). Participants (n = 79) were presented with a video of
      music therapy and the effect of the independent variables (knowledge, interest,
      strategies) on recall at two points in time were examined. Music therapy students
      were compared with music students and other therapy students (art therapy, dance
      therapy, counseling therapy) in terms of their recall of the video. Music therapy
      students achieved the highest levels of knowledge and interests. No significant
      differences were found between the three groups on the strategy component of the
      model. Overall, results were consistent with the Model and with the view that
      specific learning occurs within identified domains of knowledge or expertise. The
      results therefore, indicate efficacy for the music therapy education investigated
      in this study.

PMID- 16411789
TI  - A comparison of phonological skills of boys with fragile X syndrome and Down
      syndrome.
AB  - In this study, the authors compared the phonological accuracy and patterns of
      sound change of boys with fragile X syndrome, boys with Down syndrome, and
      typically developing mental-age-matched boys. Participants were 50 boys with
      fragile X syndrome, ages 3 to 14 years; 32 boys with Down syndrome, ages 4 to 13
      years; and 33 typically developing boys, ages 2 to 6 years, who were matched for
      nonverbal mental age to both the boys with fragile X syndrome and the boys with
      Down syndrome. All participants were administered a standardized articulation
      test, and their sound accuracy, phonological process, and proportion of whole
      word proximity scores were analyzed. Although boys with fragile X syndrome were
      delayed in their speech development, they did not differ from the typically
      developing, mental-age-matched boys in the percentage of correct early-, middle-,
      and late-developing consonants; phonological processes; or whole-word proximity
      scores. Furthermore, boys with fragile X syndrome had fewer errors on early-,
      middle-, and late-developing consonants; fewer syllable structure processes; and
      higher whole-word proximity scores than did boys with Down syndrome. Boys with
      Down syndrome also were delayed in their speech development, yet their
      phonological inventories, occurrences of phonological processes, and proportion
      of whole-word proximity scores indicated greater delays in their phonological
      development than the younger, typically developing boys. These results suggest
      that males with fragile X syndrome display phonological characteristics in
      isolated words similar to younger, typically developing children, whereas males
      with Down syndrome show greater delays as well as some developmental differences
      compared with both the males with fragile X syndrome and typically developing
      males.

PMID- 16411790
TI  - Aided and unaided speech supplementation strategies: effect of alphabet cues and
      iconic hand gestures on dysarthric speech.
AB  - PURPOSE: This study compared the influence of speaker-implemented iconic hand
      gestures and alphabet cues on speech intelligibility scores and strategy
      helpfulness ratings for 3 adults with cerebral palsy and dysarthria who differed
      from one another in their overall motor abilities. METHOD: A total of 144
      listeners (48 per speaker) orthographically transcribed sentences spoken with
      alphabet cues (aided), iconic hand gestures (unaided), and a habitual speech
      control condition; scores were compared within audio-visual and audio-only
      listening formats. RESULTS: When listeners were presented with simultaneous audio
      and visual information, both alphabet cues and hand gestures resulted in higher
      intelligibility scores and higher helpfulness ratings than the no-cues control
      condition for each of the 3 speakers. When listeners were presented with only the
      audio signal, alphabet cues and gestures again resulted in higher intelligibility
      scores than no cues for 2 of the 3 speakers. Temporal acoustic analyses showed
      that alphabet cues had consistent effects on speech production, including reduced
      speech rate, reduced articulation rate, and increased frequency and duration of
      pauses. Findings for gestures were less consistent, with marked differences noted
      among speakers. CONCLUSIONS: Results illustrate that individual differences play
      an important role in the value of supplemental augmentative and alternative
      communication strategies and that aided and unaided strategies can have similar
      positive effects on the communication of speakers with global motor impairment.

PMID- 16411791
TI  - The effects of fundamental frequency level on voice onset time in normal adult
      male speakers.
AB  - The purpose of this study was to examine the effect of fundamental frequency
      (F(0)) on stop consonant voice onset time (VOT). VOT was measured from the
      recordings of 56 young men reading phrases containing all 6 English voiced and
      voiceless stops in word-initial position across high-, medium-, and low-F(0)
      levels. Separate analyses of variance for the voiced and voiceless stops revealed
      no significant main effect for F(0) for the voiced stops but a significant F(0)
      effect for the voiceless stops. Across the voiceless stops, productions at high
      F(0)s displayed significantly shorter VOTs than productions at low or mid F(0)s.
      The findings indicated that researchers must take into account the F(0) level at
      which voiceless stop VOT is measured.

PMID- 16411792
TI  - Reviewing the literature: comments on "The Camperdown Program: outcomes of a new
      prolonged-speech treatment model" (2003) for stuttering.

PMID- 16411794
TI  - The influence of vocabulary size, phonotactic probability, and wordlikeness on
      nonword repetitions of children with and without specific language impairment.
AB  - Research has shown that children repeat high-probability phoneme sequences more
      accurately than low-probability ones. This effect attenuates with age, and its
      decrease is predicted by developmental changes in the size of the lexicon (J.
      Edwards, M. E. Beckman, & B. Munson, 2004; B. Munson, 2001; B. Munson, J.
      Edwards, & M. Beckman, 2005). This study expands on these findings by examining
      relationships between vocabulary size and repetition accuracy of nonwords varying
      in phonotactic probability by 16 children with specific language impairment
      (SLI), 16 chronological-age-matched (CA) peers with typical speech and language
      development, and 16 younger children matched with the children with SLI on
      vocabulary size (VS). As in previous research, children with SLI repeated
      nonwords less accurately than did CA children. The children with SLI and the VS
      children showed similar levels of nonword repetition accuracy. Phonotactic
      probability affected repetition accuracy more for children with SLI and VS
      children than for CA children. Regression analyses showed that measures of
      vocabulary size were the best predictor of the difference in repetition accuracy
      between high- and low-probability sequences. Analyses by items showed that
      measures of phonotactic probability were stronger predictors of repetition
      accuracy than judgments of wordlikeness. Taken together, the results support
      research demonstrating that vocabulary size mediates the influence of phonotactic
      probability on nonword repetition, perhaps due to its influence on the ongoing
      refinement of phonological categories.

PMID- 16411795
TI  - Conversational versus expository discourse: a study of syntactic development in
      children, adolescents, and adults.
AB  - In this cross-sectional investigation, syntactic development was compared in
      conversational versus expository discourse in 120 typically developing children,
      adolescents, and adults, age 7 to 49 years. Each participant was asked to discuss
      common topics such as school, family, and friends to elicit conversational
      discourse and to explain the rules and strategies of a favorite game or sport to
      elicit expository discourse. The results showed greater syntactic complexity in
      expository discourse than in conversational for all age groups, supporting the
      view that complex thought is driving the development of complex language. For
      both genres, growth in syntax continued throughout childhood and adolescence and
      into early adulthood (age 20-29 years) and remained stable into middle age (age
      40-49 years). The 2 best indicators of growth were mean length of T-unit and
      relative clause production, both of which showed age-related increases into early
      adulthood. Another variable that was sensitive to growth was the total number of
      T-units produced, a measure of language output. In general, older speakers talked
      more than younger ones regardless of genre. Despite the statistically significant
      group effects, there were wide individual differences. For example, in the
      expository genre, some of the younger children used rather elaborate syntax
      whereas some of the older adults spoke quite simply. Thus, it appears that
      individual variability can exist at all points along the age continuum, despite
      the trend toward greater syntactic complexity as a function of increasing
      chronological age.

PMID- 16411796
TI  - Perception and production of lexical tones by 3-year-old, Mandarin-speaking
      children.
AB  - The present study investigated 3-year-old children's perception and production of
      Mandarin lexical tones in monosyllabic words. Thirteen 3-year-old, Mandarin
      speaking children participated in the study. Tone perception was examined by a
      picture-pointing task, and tone production was investigated by picture naming. To
      compare children's productions with the adult forms, 4 mothers of the children
      were asked to say the same set of words to their children in a picture-reading
      activity. The children's and mothers' productions were low-pass filtered at 500
      Hz and 400 Hz, respectively, to eliminate segmental information. Ten Mandarin
      speaking judges identified the productions of tones from the filtered speech.
      Adult productions were more accurately identified than productions of the
      children. The children perceived the level, rising, and falling tones with
      relatively high accuracy. The dipping tone posed the greatest difficulty for the
      children in both perception and production.

PMID- 16411797
TI  - Prelinguistic predictors of vocabulary in young children with autism spectrum
      disorders.
AB  - PURPOSE: The goal of the current study was to identify a predictive model of
      vocabulary comprehension and production in a group of young children with autism
      spectrum disorders. Four prelinguistic behaviors were selected for consideration
      as predictors based on theoretical and empirical support for the relationship of
      these behaviors to language development. METHOD: The study used a longitudinal
      correlational design. Participants were twenty-nine 2- and 3-year-olds diagnosed
      with autism spectrum disorders. The prelinguistic behaviors-attention-following,
      motor imitation, commenting, and requesting-were measured at the initial visit.
      Vocabulary comprehension and production were measured 6 months later. RESULTS:
      Commenting was the only unique predictor of comprehension after the degree of
      cognitive delay was controlled. Both commenting and motor imitation of actions
      without objects were unique predictors of production over and above the other
      skills and when the degree of cognitive delay was controlled. CONCLUSIONS: The
      finding that both commenting and motor imitation simultaneously accounted for
      unique variance in vocabulary production is new to the literature and requires
      replication. However, results suggest that increasing behaviors that allow
      children with autism to make their current focus of attention obvious to social
      partners may be an effective approach for supporting word learning in young
      children with autism.

PMID- 16411799
TI  - Re: Law, Garrett, and Nye (2004a). "The efficacy of treatment for children with
      developmental speech and language delay/disorder: a meta-analysis".

PMID- 16411798
TI  - Effects of prelinguistic communication levels on initiation and repair of
      communication in children with disabilities.
AB  - PURPOSE: This study examined the effects of expressive and receptive language
      levels on initiated and repaired communication acts by prelinguistic children
      with developmental disabilities. METHOD: In this descriptive study, participants
      were 45 children between the ages of 3 and 6 years who had severe delays in
      expressive communication. Some children communicated with 12 or fewer spoken
      words; others communicated exclusively with gestures and vocalizations.
      Participants also had delays in receptive language, and 41 of the 45 had below
      average IQ scores. The children participated in a scripted interaction with
      examiners that was designed to provide opportunities to initiate requests and
      comments, and to repair communication breakdowns. Videotapes of these
      interactions were later coded for analysis. RESULTS: Regression models indicated
      that differences in children's expressive communication levels and receptive
      language scores significantly predicted children's commenting communication acts
      during the scripted interaction, even after the authors accounted for child IQ.
      Expressive communication level was also a significant predictor of initiated
      requests when the authors controlled for IQ. Expressive communication level
      contributed to the variance in children's repairs following communication
      breakdowns; however, this contribution was not significant. CONCLUSION:
      Differences in levels of prelinguistic communication development predict
      commenting abilities in children with developmental disabilities but do not
      appear to predict likelihood to repair communication breakdowns.

PMID- 16411801
TI  - A psychophysical evaluation of spectral enhancement.
AB  - Listeners with sensorineural hearing loss have well-documented elevated hearing
      thresholds; reduced auditory dynamic ranges; and reduced spectral (or frequency)
      resolution that may reduce speech intelligibility, especially in the presence of
      competing sounds. Amplification and amplitude compression partially compensate
      for elevated thresholds and reduced dynamic ranges but do not remediate the loss
      in spectral resolution. Spectral-enhancement processing algorithms have been
      developed that putatively compensate for decreased spectral resolution by
      increasing the spectral contrast, or the peak-to-trough ratio, of the speech
      spectrum. Several implementations have been proposed, with mixed success. It is
      unclear whether the lack of strong success was due to specific implementation
      parameters or whether the concept of spectral enhancement is fundamentally
      flawed. The goal of this study was to resolve this ambiguity by testing the
      effects of spectral enhancement on detection and discrimination of simple, well
      defined signals. To that end, groups of normal-hearing (NH) and hearing-impaired
      (HI) participants listened in 2 psychophysical experiments, including detection
      and frequency discrimination of narrowband noise signals in the presence of
      broadband noise. The NH and HI listeners showed an improved ability to detect and
      discriminate narrowband increments when there were spectral decrements (notches)
      surrounding the narrowband signals. Spectral enhancements restored increment
      detection thresholds to within the normal range when both energy and spectral
      profile cues were available to listeners. When only spectral-profile cues were
      available for frequency discrimination tasks, performance improved for HI
      listeners, but not all HI listeners reached normal levels of discrimination.
      These results suggest that listeners are able to take advantage of the local
      improvement in signal-to-noise ratio provided by the spectral decrements.

PMID- 16411802
TI  - Auditory frequency discrimination in children with specific language impairment:
      a longitudinal study.
AB  - It has been proposed that specific language impairment (SLI) is caused by an
      impairment of auditory processing, but it is unclear whether this problem affects
      temporal processing, frequency discrimination (FD), or both. Furthermore, there
      are few longitudinal studies in this area, making it hard to establish whether
      any deficit represents a developmental lag or a more permanent deficit. To
      address these issues, the authors retested a group of 10 children with SLI and 12
      control children first tested 42 months previously. At Time 1, the children with
      SLI (between 9 and 12 years of age) had significantly elevated FD thresholds
      compared to the matched controls. At Time 2, the thresholds of both groups had
      improved, but the children with SLI still had poorer FD thresholds than those of
      the controls. To assess temporal resolution, auditory backward masking was
      measured and it was found that most of the children with SLI performed as well as
      the controls, but 2 children had exceptionally high thresholds. There was also
      greater variability among the children with SLI compared to that measured among
      the controls on the FD task. These studies indicate considerable heterogeneity in
      auditory function among children with SLI and suggest that, as with auditory
      temporal deficits, difficulties in FD discrimination are important in this
      population.

PMID- 16411803
TI  - Neurophysiological indices of speech and nonspeech stimulus processing.
AB  - Auditory event-related potentials (mismatch negativity and P300) and behavioral
      discrimination were measured to synthetically generated consonant-vowel (CV)
      speech and nonspeech contrasts in 10 young adults with normal auditory systems.
      Previous research has demonstrated that behavioral and P300 responses reflect a
      phonetic, categorical level of processing. The aims of the current investigation
      were (a) to examine whether the mismatch negativity (MMN) response is also
      influenced by the phonetic characteristics of a stimulus or if it reflects purely
      an acoustic level of processing and (b) to expand our understanding of the
      neurophysiology underlying categorical perception, a phenomenon crucial in the
      processing of speech. The CVs were 2 within-category stimuli and the nonspeech
      stimuli were 2 glides whose frequency ramps matched the formant transitions of
      the CV stimuli. Listeners exhibited better behavioral discrimination to the
      nonspeech versus speech stimuli in same/different and oddball behavioral
      paradigms. MMN responses were elicited by the nonspeech stimuli, but absent to CV
      speech stimuli. Larger amplitude and earlier P300s were elicited by the nonspeech
      stimuli, while smaller and longer latency P300s were elicited by the speech
      stimulus contrast. Results suggest that the 2 types of stimuli were processed
      differently when measured behaviorally, with MMN, or P300. The better
      discrimination and clearer neurophysiological representation of the frequency
      glide, nonspeech stimuli versus the CV speech stimuli of analogous acoustic
      content support (a) categorical perception representation at the level of the MMN
      generators and (b) parallel processing of acoustic (sensory) and phonetic
      (categorical) information at the level of the MMN generators.

PMID- 16411804
TI  - Detection of hearing loss using 2f2-f1 and 2f1-f2 distortion-product otoacoustic
      emissions.
AB  - Although many distortion-product otoacoustic emissions (DPOAEs) may be measured
      in the ear canal in response to 2 pure tone stimuli, the majority of clinical
      studies have focused exclusively on the DPOAE at the frequency 2f1-f2. This study
      investigated another DPOAE, 2f2-f1, in an attempt to determine the following: (a)
      the optimal stimulus parameters for its clinical measurement and (b) its utility
      in differentiating between normal-hearing and hearing-impaired ears at low-to-mid
      frequencies (<or=2,000 Hz) when measured either alone or in conjunction with the
      2f1-f2 DPOAE. Two experiments were conducted. In Experiment 1, the effects of
      primary level, level separation, and frequency separation (f2/f1) on 2f2-f1 DPOAE
      level were evaluated in normal-hearing ears for low-to-mid f2 frequencies (700
      2,000 Hz). Moderately high-level primaries (60-70 dB SPL) presented at equal
      levels or with f2 slightly higher than f1 produced the highest 2f2-f1 DPOAE
      levels. When the f2/f1 ratio that produced the highest 2f2-f1 DPOAE levels was
      examined across participants, the mean optimal f2/f1 ratio across f2 frequencies
      and primary level separations was 1.08. In Experiment 2, the accuracy with which
      DPOAE level or signal-to-noise ratio identified hearing status at the f2
      frequency as normal or impaired was evaluated using clinical decision analysis.
      The 2f2-f1 and 2f1-f2 DPOAEs were measured from both normal-hearing and hearing
      impaired ears using 2 sets of stimulus parameters: (a) the traditional parameters
      for measuring the 2f1-f2 DPOAE (f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL) and (b) the
      new parameters that were deemed optimal for the 2f2-f1 DPOAE in Experiment 1
      (f2/f1 = 1.073, L1 and L2 = 65 dB SPL). Identification of hearing status using
      2f2-f1 DPOAE level and signal-to-noise ratio was more accurate when the new
      stimulus parameters were used compared with the results achieved when the 2f2-f1
      DPOAE was recorded using the traditional parameters. However, identification of
      hearing status was less accurate for the 2f2-f1 DPOAE measured using the new
      parameters than for the 2f1-f2 DPOAE measured using the traditional parameters.
      No statistically significant improvements in test performance were achieved when
      the information from the 2 DPOAEs was combined, either by summing the DPOAE
      levels or by using logistic regression analysis.

PMID- 16411805
TI  - Frequency discrimination and literacy skills in children with mild to moderate
      sensorineural hearing loss.
AB  - It has been suggested that specific reading disability (SRD) may be attributable
      to an impaired ability to perceive spectral differences between sounds that leads
      to a deficit in frequency discrimination and subsequent problems with language
      and literacy. The objective of the present study was three-fold. We aimed to (a)
      determine whether children with mild to moderate sensorineural hearing loss were
      impaired in their ability to discriminate frequency, (b) assess the extent to
      which any such deficits may be due to an inability to use information derived
      from phase locking, and (c) examine whether frequency discrimination abilities
      were predictive of measures of word and nonword reading and nonword repetition.
      Difference limens for frequency (DLFs) were obtained for 22 children with mild to
      moderate hearing loss (SNH group) and 22 age-matched controls (CA group) at
      central frequencies of 1 kHz, where phase-locking information is available, and 6
      kHz, where it is not. A battery of standardized tests of language and literacy
      was also administered. The SNH group exhibited significantly elevated DLFs at
      both 1 and 6 kHz relative to controls, despite considerable variability of
      thresholds in both groups. Although no group differences were found for receptive
      and expressive vocabulary, receptive grammar, and nonword reading, the SNH group
      performed worse than controls on word reading and nonword repetition, even though
      word reading scores were age-appropriate. Frequency discrimination abilities were
      associated with reading and nonword repetition across groups, but these
      correlations largely disappeared when the two groups were analyzed separately.
      Together, these results provide evidence for a dissociation between impaired
      frequency discrimination and relatively "spared" language and literacy in
      children with mild to moderate sensorineural hearing loss. These results cast
      doubt on the assertion that a deficit in frequency discrimination necessarily
      leads to marked deficits in the development of language and literacy.

PMID- 16411806
TI  - General review of tinnitus: prevalence, mechanisms, effects, and management.
AB  - Tinnitus is an increasing health concern across all strata of the general
      population. Although an abundant amount of literature has addressed the many
      facets of tinnitus, wide-ranging differences in professional beliefs and
      attitudes persist concerning its clinical management. These differences are
      detrimental to tinnitus patients because the management they receive is based
      primarily on individual opinion (which can be biased) rather than on medical
      consensus. It is thus vitally important for the tinnitus professional community
      to work together to achieve consensus. To that end, this article provides a broad
      based review of what is presently known about tinnitus, including prevalence,
      associated factors, theories of pathophysiology, psychological effects, effects
      on disability and handicap, workers' compensation issues, clinical assessment,
      and various forms of treatment. This summary of fundamental information has
      relevance to both clinical and research arenas.

PMID- 16411807
TI  - An across-frequency processing deficit in listeners with hearing impairment is
      supported by acoustic correlation.
AB  - It has been recently suggested that listeners having a sensorineural hearing
      impairment (HI) may possess a deficit in their ability to integrate speech
      information across different frequencies. When presented with a task that
      required across-frequency integration of speech patterns, listeners with HI
      performed more poorly than their normal-hearing (NH) counterparts (E. W. Healy &
      S. P. Bacon, 2002; C. W. Turner, S.-L. Chi, & S. Flock, 1999). E. W. Healy and S.
      P. Bacon (2002) also showed that performance of the listeners with HI fell more
      steeply when increasing amounts of temporal asynchrony were introduced to the
      pair of widely separated patterns. In the current study, the correlations between
      the fluctuating envelopes of the acoustic stimuli were calculated, both when the
      patterns were aligned and at various between-band asynchronies. It was found that
      the rate at which acoustic correlation fell as a function of asynchrony closely
      matched the rate at which intelligibility fell for the NH listeners. However, the
      intelligibility scores produced by the listeners with HI fell more steeply than
      the acoustic analysis would suggest. Thus, these data provide additional support
      for the hypothesis that individuals having sensorineural HI may have a deficit in
      their ability to integrate speech information present at different frequencies.

PMID- 16411808
TI  - Analysis of the balance between proliferation and apoptosis of cultured vascular
      smooth muscle cells for tissue-engineering applications.
AB  - Tissue homeostasis, the balance between cell proliferation and apoptosis, is an
      important factor in tissue engineering. We describe a new method to analyze
      markers of both proliferation and apoptosis in a single assay to monitor growth
      behavior of cell cultures. Human vascular smooth muscle cells (VSMCs) were
      cultured either on gelatin-coated tissue culture polystyrene or in three
      dimensional porous scaffolds composed of insoluble collagen and elastin. mRNA
      concentrations of cyclin E, as a marker of proliferation, and of tissue
      transglutaminase (tTG) as a marker of apoptosis, quantified by a real-time
      reverse transcriptase-polymerase chain reaction (RT-PCR) and normalized to
      porphobilinogen deaminase mRNA concentrations, were analyzed. tTG mRNA expression
      levels were increased when apoptosis was induced by tumor necrosis factor-alpha
      in combination with cycloheximide or by culturing the cells in serum-free culture
      medium. Cyclin E mRNA expression levels were less altered in these cell cultures.
      Results were compared with several reference tests to measure apoptosis including
      DNA fragmentation, annexin V staining, and light microscopy. This RT-PCR method
      could be used to characterize cell growth behavior of VSMCs in vitro. In
      addition, it was shown that this test is suitable to measure the balance between
      proliferation and apoptosis of VSMCs present in tissue-engineered constructs.

PMID- 16411809
TI  - Biocompatibility of bioresorbable poly(L-lactic acid) composite scaffolds
      obtained by supercritical gas foaming with human fetal bone cells.
AB  - The aim of this investigation was to test the biocompatibility of three
      dimensional bioresorbable foams made of poly(L-lactic acid) (PLA), alone or
      filled with hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP), with
      human primary osteoblasts, using a direct contact method. Porous constructs were
      processed by supercritical gas foaming, after a melt-extrusion of ceramic/polymer
      mixture. Three neat polymer foams, with pore sizes of 170, 310, and 600 microm,
      and two composite foams, PLA/5 wt% HA and PLA/5 wt% beta-TCP, were examined over
      a 4-week culture period. The targeted application is the bone tissue-engineering
      field. For this purpose, human fetal and adult bone cells were chosen because of
      their highly osteogenic potential. The association of fetal bone cells and
      composite scaffold should lead to in vitro bone formation. The polymer and
      composite foams supported adhesion and intense proliferation of seeded cells, as
      revealed by scanning electron microscopy. Cell differentiation toward osteoblasts
      was demonstrated by alkaline phosphatase (ALP) enzymatic activity, gamma
      carboxylated Gla-osteocalcin production, and the onset of mineralization. The
      addition of HA or beta-TCP resulted in higher ALP enzymatic activity for fetal
      bone cells and a stronger production of Gla-osteocalcin for adult bone cells.

PMID- 16411810
TI  - Novel method to examine hepatocyte-specific gene expression in a functional
      coculture system.
AB  - To mimic native tissue function, coculture systems are an extremely useful model.
      In many cases, differentiated functions can be maintained only through the
      interactions of various cell types. Therefore, methods for examining the
      interactions between cocultured cells are necessary. The assessment of cell-to
      cell cross-talk at the level of gene expression is one such method to examine
      interactions between different cell types. However, it is generally difficult to
      determine the gene expression of specific cell types in coculture without first
      separating cell populations. To overcome these obstacles, we have established a
      novel method to determine gene expression levels of a targeted cell population in
      coculture, using species-specific primers. With this approach, we were able to
      determine hepatocyte-specific gene expression of Fao cells (a rat hepatocyte cell
      line) in culture with human umbilical vein endothelial cells (HUVECs). Expression
      of both albumin and apolipoprotein A-I (apoA-I) increased time dependently for 10
      days and maintained significantly higher expression in the coculture system as
      compared with isolated Fao cells. This indicates that hepatocyte function
      increased gradually in our coculture system and could be maintained long-term,
      suggesting that the construction of mature cell-to-cell communication between the
      two cell lines required a considerable amount of time. The expression of HNF-4
      and HNF-1alpha, which are liver-enriched transcription factors, did not differ
      between the monolayer and cocultured Fao cells, suggesting that expression of HNF
      4 and HNF-1alpha was not responsible for the increased expression albumin and
      apoA-I. Our findings suggest that this novel method for the detection of gene
      expression of targeted cell populations can be a useful tool in determining the
      molecular mechanisms that regulate communication between different cell types.

PMID- 16411811
TI  - Biocompatible inkjet printing technique for designed seeding of individual living
      cells.
AB  - Inkjet printers are capable of printing at high resolution by ejecting extremely
      small ink drops. Established printing technology will be able to seed living
      cells, at micrometer resolution, in arrangements similar to biological tissues.
      We describe the use of a biocompatible inkjet head and our investigation of the
      feasibility of microseeding with living cells. Living cells are easily damaged by
      heat; therefore, we used an electrostatically driven inkjet system that was able
      to eject ink without generating significant heat. Bovine vascular endothelial
      cells were prepared and suspended in culture medium, and the cell suspension was
      used as "ink" and ejected onto culture disks. Microscopic observation showed that
      the endothelial cells were situated in the ejected dots in the medium, and that
      the number of cells in each dot was dependent on the concentration of the cell
      suspension and ejection frequency chosen. After the ejected cells were incubated
      for a few hours, they adhered to the culture disks. Using our non-heat
      generating, electrostatically driven inkjet system, living cells were safely
      ejected onto culture disks. This microseeding technique with living cells has the
      potential to advance the field of tissue engineering.

PMID- 16411813
TI  - Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac
      function after acute infarct.
AB  - The current experiments used a scaffold-based, three-dimensional, human dermal
      fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and
      preserve left ventricular (LV) function of the infarcted LV in severe combined
      immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete
      angiogenic growth factors and has been previously shown to stimulate
      angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate
      a reduction in LV function of infarcted hearts. Five groups of mice were studied,
      including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6),
      infarcted SCID mice (n = 6), infarcted mice with nonviable 3DFC (n = 6), and
      infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left
      anterior descending (LAD) coronary artery was performed by thermal ligation, and
      3DFC was sized to the damaged area and implanted onto the epicardium at the site
      of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with
      the Millar conductance catheter system (CCS). The data demonstrated that 3DFC
      treated infarcted myocardium had significantly higher ejection fractions (EFs)
      compared with infarct-only mice (58.9 +/- 10.8 versus 31.0 +/- 5.8%,
      respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were
      significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6
      +/- 11.9 versus 36.8 +/- 6.4 mmHg, respectively; p < 0.05). These results show
      that the 3DFC as a cardiac patch functioned to attenuate further loss of LV
      function accompanying acute myocardial infarct and that this may be related in
      part to myocardial revascularization.

PMID- 16411812
TI  - Galactosylated poly(vinylidene difluoride) hollow fiber bioreactor for hepatocyte
      culture.
AB  - To overcome the limitations of long-term expression of highly differentiated
      hepatocyte functions, we have developed a novel bioreactor in which hepatocytes
      are seeded in a ligand-immobilized hollow fiber cartridge. Galactosylated
      Pluronic polymer is immobilized on poly(vinylidene difluoride) (PVDF) hollow
      fiber surface through an adsorption scheme yielding a substrate with hepatocyte
      specific ligand and a hydrophilic surface layer, which can resist nonspecific
      protein adsorption and facilitate cell binding to the galactose ligand.
      Interestingly, the galactosylated PVDF hollow fiber shows enhanced serum albumin
      diffusion across the membrane. Freshly isolated rat hepatocytes were seeded and
      cultured in the extralumenal space of the hollow fiber cartridge for 18 days in a
      continuously circulated system. Albumin secretion function of the seeded
      hepatocytes was monitored by analyzing circulating medium by enzyme-linked
      immunosorbent assay. Urea synthesis and P-450 function (7-ethoxycoumarin
      dealkylase activity) were measured periodically by doping the circulating medium
      with NH4Cl and 7-ethoxycoumarin, respectively. Hepatocytes cultured on
      galactosylated PVDF hollow fibers maintained better albumin secretion and P-450
      functions than on unmodified and serum-coated PVDF hollow fibers when cultured in
      serum-containing medium. Morphological examination by scanning electron
      microscopy showed that hepatocytes cultured on galactosylated PVDF hollow fibers
      developed significant aggregation, in contrast to those cultured on unmodified
      PVDF fibers or on serum-coated PVDF fibers. Transmission electron microscopy
      images revealed that tight junctions and canaliculus-like structures formed in
      these aggregates. These results suggest the potential application of this
      galactosylated PVDF hollow fiber cartridge for the design of a bioartificial
      liver assist device.

PMID- 16411814
TI  - Surface modification by complexes of vitronectin and growth factors for serum
      free culture of human osteoblasts.
AB  - Cell attachment, expansion, and migration in three-dimensional biomaterials are
      crucial steps for effective delivery of osteogenic cells into bone defects.
      Complexes composed of vitronectin (VN), insulin-like growth factors (IGFs), and
      insulin growth factor-binding proteins (IGFBPs) have been reported to enhance
      cell attachment, proliferation, and migration in a variety of cell lines in
      vitro. The aim of this study was to examine whether prebound complexes of VN and
      IGFs +/- IGFBPs could facilitate human osteoblast serum-free expansion in vitro
      and enhance cell attachment, proliferation, and migration in three-dimensional
      biomaterial constructs. Human osteoblasts derived from alveolar bone chips and
      the established human osteoblast cell line Saos-2 were used. These cells were
      seeded on tissue culture plates and porous scaffolds of type I collagen sponges
      and polyglycolic acid (PGA), which had been coated with VN +/- IGFBP-5 +/- IGF-I.
      Cell attachment, proliferation, and migration were evaluated by cell counting,
      confocal microscopy, and scanning electron microscopy. The number of attached
      human osteoblasts was significantly higher in VN-coated polystyrene culture
      dishes. Furthermore, significant increases in cell proliferation were observed
      when growth factors were bound to these surfaces in the presence of VN. In the
      two scaffold materials examined, greater cell attachment was found in type I
      collagen sponges compared with PGA scaffolds. However, coating the scaffolds with
      complexes composed of VN + IGF-I or VN + IGFBP-5 + IGF-I enhanced cell attachment
      on PGA. Moreover, the presence of VN + IGFBP-5 + IGF-I resulted in significantly
      greater osteoblast migration into deep pore areas as compared with untreated
      scaffolds or scaffolds treated with fetal calf serum. These results demonstrated
      that complexes of VN + IGFBP-5 + IGF-I can be used to expand osteoblasts in vitro
      under serum-free conditions and enhance the attachment and migration of human
      osteoblasts in three-dimensional culture. This in turn suggests a potential
      application in surface modification of biomaterials for tissue reconstruction.

PMID- 16411815
TI  - Wavy-walled bioreactor supports increased cell proliferation and matrix
      deposition in engineered cartilage constructs.
AB  - Hydrodynamic forces in bioreactors can decisively influence extracellular matrix
      deposition in engineered cartilage constructs. In the present study, the reduced
      fluid shear, high-axial mixing environment provided by a wavy-walled bioreactor
      was exploited in the cultivation of cartilage constructs using polyglycolic acid
      scaffolds seeded with bovine articular chondrocytes. Increased growth as defined
      by weight, cell proliferation and extracellular matrix deposition was observed in
      cartilage constructs from wavy-walled bioreactors in comparison with those from
      spinner flasks cultured under the same conditions. The wet weight composition of
      4-week constructs from the wavy-walled bioreactor was similar to that of spinner
      flask constructs, but the former were 60% heavier due to equally higher
      incorporation of extracellular matrix and 30% higher cell population. It is most
      likely that increased construct matrix incorporation was a result of increased
      mitotic activity of chondrocytes cultured in the environment of the wavy-walled
      bioreactor. A layer of elongated cells embedded in type I collagen formed at the
      periphery of wavy-walled bioreactor and spinner flask constructs, possibly as a
      response to local shear forces. On the basis of the robustness and
      reproducibility of the extracellular matrix composition of cartilage constructs,
      the wavy-walled bioreactor demonstrated promise as an experimental cartilage
      tissue-engineering vessel. Increased construct growth in the wavy-walled
      bioreactor may lead to enhanced mechanical properties and expedited in vitro
      cultivation.

PMID- 16411816
TI  - Tissue engineering of nearly transparent corneal stroma.
AB  - We determined whether a polyglycolic acid (PGA) scaffold bearing an adherent
      corneal stromal cell insert could be integrated into the ultrastructure of rabbit
      corneal stroma without compromising tissue transparency. Stromal cells were
      isolated from 10 newborn rabbits and expanded by tissue culture. After reaching
      confluence, the cells were harvested and mixed with nonwoven PGA fibers to form
      cell-scaffold constructs. After 1 week of culturing, they were implanted into the
      corneal stroma of female rabbit recipients. Green fluorescent protein (GFP)
      expression in transplanted corneal stromal cells was monitored at the protein
      level to determine cellular origin in the reconstructed stroma. Eight weeks after
      implantation, transmission electron microscopy and histological evaluation were
      performed on stromal tissue. Insertion of PGA scaffold alone served as a sham
      control. After stromal implantation, implants gradually became transparent over
      an 8-week period. During this time stromal histology was gradually restored, as
      collagen fibril organization approached that of their normal counterpart. GFP
      labeled corneal stromal cells were preponderant in the regions bearing inserted
      scaffolds, suggesting that they were derived from the implants rather than from
      neighboring corneal stromal cells. No reconstructed stroma developed in regions
      where naked PGA was implanted instead. We conclude that intrastromal implantation
      of PGA fiber scaffold implants bearing corneal stromal cells is a useful
      procedure for corneal stromal tissue reconstruction because, over an 8-week
      period, the implants become progressively more transparent. Marked losses of
      translucence during this period combined with restoration of ultrastructure
      indicate that the implants provide the functions needed for deturgescing
      initially swollen stroma.

PMID- 16411817
TI  - Injectable liver: a novel approach using fibrin gel as a matrix for culture and
      intrahepatic transplantation of hepatocytes.
AB  - Cell transplantation and tissue engineering with liver cells are currently under
      investigation as experimental therapies for certain liver diseases. In this study
      we evaluated a fibrin-based gel matrix as carrier for hepatocytes in culture.
      Furthermore, a novel technique for direct intrahepatic injection of fibrin gel
      immobilized hepatocytes was developed and evaluated in a rat model. Hepatocytes
      were harvested from rats. Fibrin matrix was generated with modified fibrin
      sealant. Cells, in medium containing epidermal growth factor and insulin, were
      seeded in a drop of fibrin matrix onto plastic culture dishes. Cell numbers were
      assessed by DNA content. Hepatocyte differentiation was evaluated by reverse
      transcription-polymerase chain reaction (RT-PCR) and immunohistology (IH) for
      cytokeratin (CK)-18 and albumin. PKH26-labeled fibrin gel-immobilized hepatocytes
      were transplanted into liver by direct injection underneath the capsule.
      Fluorescence microscopy of explanted liver was performed to identify PKH26+ donor
      cells. Neotissue was characterized by IH for the markers CK-18, ED1, and desmin.
      Culture in a fibrin matrix allowed stable cell numbers and three-dimensional
      neotissue formation. RT-PCR and IH showed preservation of liver-specific markers
      CK-18 and albumin in vitro. Transplanted cells were identified by fluorescence
      microscopy after 2 and 7 days. CK-18 and desmin staining showed integration of
      hepatocytes and hepatic stellate cells into the host liver. Fibrin matrix is an
      appropriate environment for hepatocytes in culture. Direct intrahepatic injection
      of fibrin gel-immobilized hepatocytes is technically feasible. We conclude that
      fibrin gel immobilization is an attractive tool for the development of tissue
      engineering-based liver support systems.

PMID- 16411818
TI  - Use of mesenchymal stem cells to facilitate bone regeneration in normal and
      chemotherapy-treated rats.
AB  - Reconstructing segmental bone defects after resection of malignant bone tumors is
      a long-standing clinical problem. Treatment of bone tumors such as osteosarcoma
      involves chemotherapy. These chemotherapeutic agents are potent inhibitors of
      cell division and these drugs may affect regeneration of bone from
      osteoprogenitor cells. It may be possible to reconstruct segmental bone defects
      by a tissue-engineering approach. The aim of this study was to investigate the
      use of mesenchymal stem cells (MSCs) in a fibrin glue carrier to enhance bone
      regeneration after chemotherapy. Bone marrow was harvested from young adult male
      rats of the Wistar strain; stem cells were isolated and expanded. Bone
      regeneration in normal and chemotherapy-treated rats was investigated in 1.5-mm
      rat femoral defects created by osteotomizing the femur and stabilizing the
      femoral fragments by external fixation. The osteotomy gap was left either
      unfilled, filled with fibrin glue alone, or filled with glue containing stem
      cells. Bone formation within the gap was determined by radiography, dual-energy X
      ray absorptiometry, and histology. It was shown that MSCs encapsulated within
      fibrin glue could remain viable for up to 96 h in tissue culture. Chemotherapy
      significantly reduced bone formation in unfilled defects and defects filled only
      with fibrin glue. When MSCs were used in conjunction with fibrin glue, even in
      non-chemotherapy-treated rats bone formation in the gap was significantly
      increased. Using stem cells, the effects of chemotherapy on bone formation could
      be alleviated by bone formation in the gap similar to that seen in non
      chemotherapy-treated animals with MSCs. These studies demonstrated that a tissue
      engineering approach in patients undergoing chemotherapy may be beneficial for
      treating segmental bone defects after tumor resection.

PMID- 16411819
TI  - Collagen-coupled poly(2-hydroxyethyl methacrylate)-Si(111) hybrid surfaces for
      cell immobilization.
AB  - To improve the biocompatibility of silicon-based implantable micro- and
      nanodevices, and to tailor silicon surfaces for controlled cell immobilization,
      well-defined functional polymer-Si(111) hybrids, consisting of nearly
      monodispersed poly(2-hydroxyethyl methacrylate [P(HEMA)] with covalently coupled
      collagen and tethered (Si-C bonded) on the silicon surfaces, were prepared. HEMA
      was graft polymerized on the hydrogen-terminated Si(111) surface (Si-H surface)
      via surface-initiated atom transfer radical polymerization (ATRP) to give rise to
      the Si-g-P(HEMA) hybrid. The active chloride end groups preserved throughout the
      ATRP process and the chloride groups converted from some (approximately 20%) of
      the OH groups of the P(HEMA) brushes were used as the leaving groups for
      nucleophilic reaction with the -NH2 groups of collagen to give rise to the Si-g
      P(HEMA)-collagen surface conjugates. These hybrid surfaces were evaluated by
      culturing 3T3 fibroblasts. The biocompatible Si-g-P(HEMA) hybrid surface resisted
      attachment and growth of this cell line. The Si-g-P(HEMA)-collagen hybrid
      surfaces, on the other hand, exhibited good cell adhesion and growth
      characteristics, and the extent of cell immobilization could be controlled by
      adjusting the amount of immobilized collagen. Thus, incorporating the collagen
      coupled P(HEMA) onto silicon surfaces via robust Si-C bonds may endow the silicon
      substrates with new and interesting properties for potential applications in
      silicon-based implantable devices, such as molecular sensors and biochips.

PMID- 16411820
TI  - Artificial design of three-dimensional retina-like tissue from dissociated cells
      of the mammalian retina by rotation-mediated cell aggregation.
AB  - The goal of this study was to establish a reliable three-dimensional culture
      system for the mammalian retina that allows the analysis of retinal function and
      dysfunction. To produce three-dimensional retinal tissues in vitro, dissociated
      retinal cells of neonatal rats were maintained in culture dishes on a self-made
      orbital shaker. On the basis of well-defined rotation conditions, dissociated
      free-floating cells reaggregate in the center of the culture dish to form a
      multicellular cluster. Subsequently, cells begin to proliferate, whereby they
      form spherelike retinal tissues that grow to a size of 180-210 microm.
      Immunohistochemical characterization of mature retinal spheres revealed the
      presence of ganglion cells, amacrine cells, Muller cells, and rod photoreceptors,
      which are arranged in different retina-like layers. Although a small number of
      cells undergo programmed cell death, retinal spheres remain viable for at least
      35 days in culture as revealed by fluorescein diacetate and TUNEL staining.
      Because most biological processes involved in tissue organization such as
      proliferation, differentiation, apoptosis, and survival are also observable in
      retinal spheres, the presented novel mammalian three-dimensional culture system
      is not only an outstanding model for basic research but may also be of great
      benefit for stem cell tissue engineering and the pharmaceutical industry.

PMID- 16411821
TI  - Connectivity patterns in neuronal networks of experimentally defined geometry.
AB  - Experimental control over the position and connectivity pattern of neurons on a
      surface is of central interest for applications in biotechnology, such as cell
      based biosensors and tissue engineering. By restricting neuronal networks to a
      simple grid pattern, a drastic reduction of network complexity can be achieved
      relative to networks on homogeneous substrates. Therefore, patterned neuronal
      networks are also a valuable tool in research on neuronal signal transduction.
      Microcontact printing has emerged as a simple and efficient method for surface
      patterning to direct cellular attachment. Although the formation of synaptic
      contacts in networks of rat cortical cells on such surfaces has been
      demonstrated, evidence of more complex circuits has been lacking. Triple patch
      clamp measurements were performed to analyze connectivity in neuronal networks
      complying with a grid-shaped micropattern. Cells adhered stringently to the
      pattern and interconnected to a range of different types of circuits: linear
      connections, feedback loops, as well as branching and converging pathways. We
      conclude that in spite of the severe geometric restrictions, a complex repertoire
      of different connectivity patterns can form along the provided pathways. At the
      same time, network complexity is kept low enough to allow the study of these
      patterns at the resolution of single cell-cell contacts.

PMID- 16411822
TI  - Synthesis and in vitro evaluation of enzymatically cross-linked elastin-like
      polypeptide gels for cartilaginous tissue repair.
AB  - Genetically engineered elastin-like polypeptide (ELP) hydrogels offer unique
      promise as scaffolds for cartilage tissue engineering because of the potential to
      promote chondrogenesis and to control mechanical properties. In this study, we
      designed and synthesized ELPs capable of undergoing enzyme-initiated gelation via
      tissue transglutaminase, with the ultimate goal of creating an injectable, in
      situ cross-linking scaffold to promote functional cartilage repair. Addition of
      the enzyme promoted ELP gel formation and chondrocyte encapsulation in a
      biocompatible process, which resulted in cartilage matrix synthesis in vitro and
      the potential to contribute to cartilage mechanical function in vivo. A
      significant increase in the accumulation of sulfated glycosaminoglycans was
      observed, and histological sections revealed the accumulation of a cartilaginous
      matrix rich in type II collagen and lacking in type I collagen, indicative of
      hyaline cartilage formation. These results provide evidence of chondrocytic
      phenotype maintenance for cells in the ELP hydrogels in vitro. In addition, the
      dynamic shear moduli of ELP hydrogels seeded with chondrocytes increased from
      0.28 to 1.7 kPa during a 4-week culture period. This increase in the mechanical
      integrity of cross-linked ELP hydrogels suggests restructuring of the ELP matrix
      by deposition of functional cartilage extracellular matrix components.

PMID- 16411823
TI  - Adipose tissue-derived mesenchymal stem cells acquire bone cell-like
      responsiveness to fluid shear stress on osteogenic stimulation.
AB  - To engineer bone tissue, mechanosensitive cells are needed that are able to
      perform bone cell-specific functions, such as (re)modeling of bone tissue. In
      vivo, local bone mass and architecture are affected by mechanical loading, which
      is thought to provoke a cellular response via loading-induced flow of
      interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal
      stem cells for bone tissue engineering, and is available in abundant amounts
      compared with bone marrow. We studied whether adipose tissue-derived mesenchymal
      stem cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow
      (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a bone cell
      like response to fluid shear stress as a result of PFF after the stimulation of
      osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric
      oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase
      1, gene expression in osteogenically stimulated AT-MSCs. These data suggest that
      AT-MSCs acquire bone cell-like responsiveness to pulsating fluid shear stress on
      1,25-dihydroxyvitamin D3-induced osteogenic differentiation. ATMSCs might be able
      to perform bone cell-specific functions during bone (re)modeling in vivo and,
      therefore, provide a promising new tool for bone tissue engineering.

PMID- 16411824
TI  - Repair of osteochondral defects in rabbits with ectopically produced cartilage.
AB  - Cartilage has poor regenerative capacity. Donor site morbidity and interference
      with joint homeostasis should be considered when applying the autologous
      chondrocyte transplantation technique. The use of ectopically produced cartilage,
      derived from periosteum, might be a novel method to heal cartilage defects.
      Ectopic cartilage was produced by dissecting a piece of periosteum from the tibia
      of rabbits. After 14 days the reactive tissue at the dissection site was
      harvested and a graft was cored out and press-fit implanted in an osteochondral
      defect in the medial condyle of the femur with or without addition of hyaluronan.
      After 3 weeks and 3 months the repair reaction was evaluated by histology.
      Thionine- and collagen type II-stained sections were evaluated for graft
      viability, ingrowth of the graft, and joint surface repair. Empty defects
      remained empty 3 weeks after implantation, ectopic cartilage filled the defect to
      the level of the surrounding cartilage. Histologically, the grafts were viable,
      consisting mainly of cartilage, and showed a variable pattern of ingrowth. Three
      months after implantation empty defects with or without hyaluronan were filled
      primarily with fibrocartilaginous tissue. Defects treated with ectopic cartilage
      contained mixtures of fibrocartilaginous and hyaline cartilage. Sometimes a
      tidemark was observed in the new articular cartilage and the orientation of the
      cells resembled that of healthy articular cartilage. Subchondral bone repair was
      excellent. The modified O'Driscoll scores for empty defects without and with
      hyaluronan were 12.7 +/- 6.4 and 15.3 +/- 3.2; for treated defects scores were
      better (15.4 +/- 3.9 and 18.2 +/- 2.9). In this conceptual study the use of
      ectopic cartilage derived from periosteum appears to be a promising novel method
      for joint surface repair in rabbits.

PMID- 16411825
TI  - Conformal coating of mammalian cells immobilized onto magnetically driven beads.
AB  - A novel cell bead system, comprising a magnetic core, a spherical annulus of
      agarose-immobilized cells, all conformally coated within a synthetic polymer, is
      proposed as a means of immunoisolating mammalian cells in a system that provides
      a balance between low total implant volume, retrievability, and diffusion
      limitations. A successful immunoisolation system could be used to transplant
      cells without eliciting an inappropriate host response. Chinese hamster ovary
      (CHO) cells were immobilized at the periphery of large (approximately 2 mm)
      agarose beads containing inert magnetic cores (< or = 1 mm) and coated in a
      hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) copolymer by interfacial
      precipitation. The beads were coated in liquid gradients containing polyethylene
      glycol 200 (PEG) or bromooctane. Although many cells were adversely affected by
      the coating process, the cells that did survive (30-50% of those loaded into the
      beads) remained viable for a period of at least 2 weeks. This viability was much
      higher than achieved previously because of a number of factors, such as the
      aqueous agarose, the hydrophobic bromooctane intermediate layer, and faster
      coating times that minimize the exposure of the cells to organic solvents. Also,
      a mathematical model was used to describe oxygen transport within the annular
      agarose beads. These results provide evidence that the proposed geometry and the
      fabrication approach may be useful for a variety of applications that involve
      cell encapsulation.

PMID- 16411826
TI  - Collagen/poloxamine hydrogels: cytocompatibility of embedded HepG2 cells and
      surface-attached endothelial cells.
AB  - The effects of cross-linked poloxamine hydrogels on the cellular function of
      embedded HepG2 cells and surface-attached endothelial cells were assessed. HepG2
      cells embedded within collagen/poloxamine-methacrylate gel survived photo-cross
      linking (MTT viability, 78%). There was a gradual increase in cell number during
      the first week. The cumulative secretion of alpha1-antitrypsin by HepG2 cells
      showed an almost linear profile. However, lower levels for the
      collagen/poloxamine-methacrylate matrix were observed when compared with
      collagen. Endothelial cells attached poorly to poloxamine gels without collagen
      (alamarBlue reduction ranged from 36 to 63%) and did not spread well. The
      addition of collagen led to spread cells and alamarBlue reduction levels of 75
      93% (24 h after seeding). On day 5, some detachment was noted through analysis of
      vascular endothelial cadherin staining. Finally, the collagen-containing matrix
      was used to prepare cylindrical modules containing HepG2 cells to show the
      utility of this material in modular tissue constructs. A fluorescent cytoplasmic
      tracer, Vybrant CFDA SE, showed that embedded cells remained viable for more than
      2 months, confirming the good cytocompatibility of collagen/poloxamine
      methacrylate in the form of modules. The suitability of these modules for
      preparing uniform, scaleable, and vascularized constructs remains to be
      demonstrated.

PMID- 16411827
TI  - Survival and proliferative ability of various living cell types after laser
      induced forward transfer.
AB  - The survival, proliferation, and differentiation of freshly isolated and cultured
      cells were studied after absorbing film-assisted laser-induced forward transfer.
      Rat Schwann and astroglial cells and pig lens epithelial cells were used for
      transfer and the cells were cultured for 2 weeks after laser-pulsed transfer. All
      three cell types survived, proliferated, and differentiated under cell culture
      conditions and regained their original phenotype a few days after cell transfer.
      Time resolution studies have shown that the time required to accelerate the jets
      and droplets containing the cells was less than 1 micros and that the estimated
      minimum average acceleration of those ejected cells that reached a constant
      velocity was approximately 10(7) x g. This suggests that the majority of studied
      cells tolerated the extremely high acceleration at the beginning of the ejection
      and the deceleration during impact on the acceptor plate without significant
      damage to the original phenotype. These results suggest that the absorbing film
      assisted laser-induced forward transfer technique appears to be suitable for
      several potential applications in tissue engineering and the biomedical tissue
      repair technologies.

PMID- 16411829
TI  - Mechanical stimulation of MC3T3 osteoblastic cells in a bone tissue-engineering
      bioreactor enhances prostaglandin E2 release.

PMID- 16411830
TI  - Adipose tissue engineering based on mesenchymal stem cells and basic fibroblast
      growth factor in vitro.
AB  - Despite the clinical need for reconstructive and plastic surgery, the supply of
      engineered adipose tissue equivalents still remains a challenge. As yet, only
      preadipocytes have been applied as a cell material for the in vitro tissue
      engineering of fat. Herein, we report the establishment of a three-dimensional (3
      D) long-term cell culture, using bone marrow-derived mesenchymal stem cells
      (MSCs) as an alternative cell source and custom-made poly(lactic-co-glycolic
      acid) (PLGA) scaffolds as a cell carrier. Cell-polymer constructs were cultivated
      for 4 weeks in both the absence and presence of basic fibroblast growth factor
      (bFGF), which was previously shown to strongly enhance the adipogenesis of MSCs
      in conventional 2-D short-term culture. A striking enhancement of the adipogenic
      differentiation of MSCs and tissue development caused by bFGF in the 3-D culture
      was observed by osmium tetroxide histology and scanning electron microscopy. At
      the molecular level, reflecting the increased accumulation of lipids, bFGF
      increased the enzymatic activity of glycerol-3-phosphate dehydrogenase, a late
      marker of adipogenesis, and the expression of adipocyte-specific genes peroxisome
      proliferator activated receptor-gamma2 (PPARgamma2) and glucose transporter-4
      (GLUT4), as assessed by reverse transcription-polymerase chain reaction. This
      study demonstrates that the use of bone marrow-derived MSCs, especially in
      combination with bFGF, may represent a promising approach to adipose tissue
      engineering.

PMID- 16411828
TI  - Development of a closed bioreactor system for culture of tissue-engineered skin
      at an air-liquid interface.
AB  - A bioreactor has been developed for the production of tissue-engineered skin at
      an air-liquid interface for clinical and experimental use. In this closed system,
      scaffold and bioreactor sterilization, cell seeding, and medium perfusion were
      all performed with a peristaltic pump. Natural and synthetic dermal substitutes
      were seeded directly with skin cells without opening the bioreactor and fed
      either by continuous medium perfusion or by batch-feed. The system was validated
      by monoculture of human dermal fibroblasts and keratinocytes and the coculture of
      both cell types in acellular human dermis, Azowipes, electrospun polystyrene, and
      an electrospun composite of polystyrene and poly-DL-lactide fibers. A comparison
      was made of culture at an air-liquid interface versus submerged culture and of
      medium change by continuous perfusion versus batch-feed. Fibroblast and
      endothelial cells showed greater viability under submerged rather than air-liquid
      conditions whereas keratinocytes favored culture at an air-liquid interface as
      did cocultured keratinocytes and fibroblasts. Total cellular viability for
      reconstructed skin with keratinocytes and fibroblasts was greatest with
      continuous perfusion rather than batch-feed and with electrospun scaffolds
      compared with acellular human dermis. The bioreactor could also be easily
      configured to give replicate small areas for experimental use or one continuous
      area of construct for clinical use.

PMID- 16411831
TI  - Effects of dynamic fluid pressure on chondrocytes cultured in biodegradable
      poly(glycolic acid) fibrous scaffolds.

PMID- 16411832
TI  - Injectable biopolymers enhance angiogenesis after myocardial infarction.
AB  - Novel strategies by which to repair ischemic myocardium after myocardial
      infarction include the use of three-dimensional polymer scaffolds. A comparative
      study was carried out to assess the therapeutic potential of fibrin, collagen I,
      and Matrigel as injectable biopolymers for repair after myocardial infarction.
      Using a rat model of left coronary artery occlusion followed by reperfusion,
      local injection of the biopolymers into the infarct zone yielded significantly
      higher levels of capillary formation, when compared with the saline control
      group, at 5 weeks posttreatment. However, the degree of angiogenesis was not
      significantly different among the biopolymers. In addition, the collagen
      biopolymer significantly enhanced infiltration of myofibroblasts into the infarct
      area when compared with the control group. The results of this study highlight
      the potential clinical benefit of these biopolymers as injectable scaffolds or
      cell delivery vehicles to the infarct zone after infarction.

PMID- 16411833
TI  - Influence of RGD-loaded titanium implants on bone formation in vivo.
AB  - Little is known about the ability of peptide-coated surfaces to influence cell
      responses in vivo. Many studies have demonstrated that peptide-modified surfaces
      influence cell responses in vitro. Integrins, which bind specifically short
      peptide sequences, are responsible for these cell responses. In this way,
      information can be transmitted to the nucleus through several cytoplasmic
      signaling pathways. The peptide sequence Arg-Gly-Asp (RGD peptide) plays an
      important role in osteoblast adhesion. The present study was designed to
      investigate new bone formation in a porous titanium (Ti) fiber mesh implant,
      which was coated with cyclic RGD peptide. The RGD-Ti implants were inserted into
      the cranium of a rabbit and were compared with porous titanium fiber mesh disks
      without RGD sequence (Ti) and with an open control defect. Histologic and
      histomorphometric examinations were performed 2, 4, and 8 weeks postoperatively.
      A significant increase in bone formation, or bone ingrowth, was seen in the RGD
      Ti group compared with the Ti group after 4 and 8 weeks. All control defects
      stayed open in all three periods. It was concluded that the use of cyclic RGD
      peptide in combination with titanium fiber mesh has a positive effect on bone
      formation in vivo in a rabbit animal model.

PMID- 16411834
TI  - Novel biphasic elastomeric scaffold for small-diameter blood vessel tissue
      engineering.
AB  - Compliance mismatch, thrombosis, and long culture times in vitro remain important
      challenges to the clinical implementation of a tissue-engineered small-diameter
      blood vessel (SDBV). To address these issues, we are developing an implantable
      elastomeric and biodegradable biphasic tubular scaffold. The scaffold design uses
      connected nonporous and porous phases as a basis to mimic, respectively, the
      intimal and medial layers of a blood vessel. Biphasic scaffolds were fabricated
      from poly(diol citrate), a novel class of biodegradable polyester elastomer.
      Scaffolds were characterized for tensile and compressive properties, burst
      pressure, compliance, foreign body reaction (via subcutaneous implantation in
      rats), and cell distribution and differentiation (via histology, scanning
      electron microscopy, and immunohistochemistry). Tensile tests, burst pressure,
      and compliance measurements confirm that the incorporation of a nonporous phase
      to create a "skin" connected to the porous phase of a scaffold can provide bulk
      mechanical properties that are similar to those of a native vessel. Compression
      tests confirm that the scaffolds are soft and recover from deformation.
      Subcutaneously implanted poly(diol citrate) porous scaffolds produce a thin
      fibrous capsule and allow for tissue ingrowth. In vitro culture of tubular
      biphasic scaffolds seeded with human aortic smooth muscle cells (HASMCs) and
      endothelial cells (HAECs) demonstrates the ability of this design to support cell
      compartmentalization, coculture, and cell differentiation. The newly formed HAEC
      monolayer stained positive for von Willebrand factor whereas collagen- and
      calponin-positive HASMCs were present in the porous phase.

PMID- 16411835
TI  - Sequential growth factor application in bone marrow stromal cell ligament
      engineering.
AB  - In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture
      medium supplementation, mimicking the biochemical environment in which cells
      optimally proliferate and differentiate. We hypothesize that the sequential
      administration of growth factors to first proliferate and then differentiate
      BMSCs cultured on silk fiber matrices will support the enhanced development of
      ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from
      purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded
      matrices were divided into three groups for 5 days of static culture, with medium
      supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth
      factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium
      supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C
      for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and
      ELISA for collagen type I of all sample groups were performed. Results indicated
      that BT supported the greatest cell ingrowth after 14 days of culture in addition
      to the greatest cumulative collagen type I expression measured by ELISA.
      Sequential growth factor application promoted significant increases in collagen
      type I transcript expression from day 5 of culture to day 14, for five of six
      groups tested. All T-supplemented samples surpassed their respective control
      samples in both cell ingrowth and collagen deposition. All samples supported
      spindle-shaped, fibroblast cell morphology, aligning with the direction of silk
      fibers. These findings indicate significant in vitro ligament development after
      only 14 days of culture when using a sequential growth factor approach.

PMID- 16411836
TI  - Effect of initial cell-seeding density on postoperative cell number and
      dispersion.

PMID- 16411837
TI  - Current issues in the regulation of human tissue-engineering products in the
      European Union.
AB  - Tissue engineering (TE) is an emerging technology that combines expertise in life
      sciences, clinical medicine, and engineering. Current challenges in TE include
      anticipating and streamlining appropriate regulation with product development.
      Consequently this study has focused on views of developers, companies, and
      regulators on biological risks of TE products, aspects of commercial
      applications, and patentability. Most concerns about TE products focus on risk of
      cancer formation, infection risk, and rejection risk. Thus, at the present time,
      product developers should follow guidelines for medicinal products, in order to
      address product safety at an adequate level. According to the data of the present
      study, cell and biomaterial products, manipulated cells, and scaffolds appear to
      be the primary interest for commercial product development. In contrast,
      producing services were not considered as interesting. Constraints are also
      imposed by patentability, which stipulates demands for technical performance and
      highlights ethical issues, which are difficult to address.

PMID- 16411865
TI  - Obesity and reproductive health.

PMID- 16411866
TI  - Are meal replacements an effective clinical tool for weight loss?
AB  - Clinical trials show partial meal replacement products to be safe, acceptable and
      effective when used as part of an overall low-energy diet.

PMID- 16411867
TI  - The silent infection: should we be testing for perinatal hepatitis C and, if so,
      how?
AB  - We recommend screening all infants whose mothers are HCV antibody-positive.

PMID- 16411868
TI  - The prevalence and impact of overweight and obesity in an Australian obstetric
      population.
AB  - OBJECTIVE: To assess the prevalence and impact of overweight and obesity in an
      Australian obstetric population. DESIGN, SETTING AND PARTICIPANTS: The Mater
      Mother's Hospital (MMH), South Brisbane, is an urban tertiary referral maternity
      hospital. We reviewed data for the 18 401 women who were booked for antenatal
      care at the MMH, delivered between January 1998 and December 2002, and had a
      singleton pregnancy. Of those women, 14 230 had an estimated pre-pregnancy body
      mass index (BMI) noted in their record; 2978 women with BMI < or = 20 kg/m2 were
      excluded from further study; the remaining 11 252 women were divided into four
      categories: "normal" (BMI 20.01-25 kg/m(2)), "overweight" (BMI 25.01-30 kg/m(2)),
      "obese" (BMI 30.01-40 kg/m(2)) and "morbidly obese" (BMI > 40 kg/m(2)). MAIN
      OUTCOME MEASURES: Prevalence of overweight and obesity in an obstetric
      population; maternal, peripartum and neonatal outcomes associated with raised
      BMI. RESULTS: Of the 14 230 women, 6443 (45%) were of normal weight, and 4809
      (34%) were overweight, obese or morbidly obese. Overweight, obese and morbidly
      obese women were at increased risk of adverse outcomes (figures represent
      adjusted odds ratio [AOR] [95% CI]): hypertensive disorders of pregnancy
      (overweight 1.74 [1.45-2.15], obese 3.00 [2.40-3.74], morbidly obese 4.87 [3.27
      7.24]); gestational diabetes (overweight 1.78 [1.25-2.52], obese 2.95 [2.05
      4.25], morbidly obese 7.44 [4.42-12.54]); hospital admission longer than 5 days
      (overweight 1.36 [1.13-1.63], obese 1.49 [1.21-1.86], morbidly obese 3.18 [2.19
      4.61]); and caesarean section (overweight 1.50 [1.36-1.66], obese 2.02 [1.79
      2.29], morbidly obese 2.54 [1.94-3.32]). Neonates born to obese and morbidly
      obese women had an increased risk of birth defects (obese 1.58 [1.02-2.46],
      morbidly obese 3.41 [1.67-6.94]); and hypoglycaemia (obese 2.57 [1.39-4.78],
      morbidly obese 7.14 [3.04-16.74]). Neonates born to morbidly obese women were at
      increased risk of admission to intensive care (2.77 [1.81-4.25]); premature
      delivery (< 34 weeks' gestation) (2.13 [1.13-4.01]); and jaundice (1.44 [1.09
      1.89]). CONCLUSIONS: Overweight and obesity are common in pregnant women.
      Increasing BMI is associated with maternal and neonatal outcomes that may
      increase the costs of obstetric care. To assist in planning health service
      delivery, we believe that BMI should be routinely recorded on perinatal data
      collection sheets.

PMID- 16411869
TI  - Effect of dog-walking on autonomic nervous activity in senior citizens.
AB  - OBJECTIVE: To compare changes in autonomic nervous activity in healthy senior
      individuals while walking with and without a dog, and during routine activities
      at home and periods of interacting with the dog at home. DESIGN: Controlled
      crossover study. PARTICIPANTS AND SETTING: 13 healthy volunteers (3 men, 10
      women; mean age, 67.5 years) who walked in a park adjacent to Gunma University,
      Japan, and 4 volunteers among these who underwent monitoring in their own homes.
      INTERVENTIONS: Heart rate variability was monitored continuously by means of a
      palm-sized electrocardiographic monitor (which facilitated spectral analysis of
      the RR interval) while participants walked for 30 minutes (first with, then
      without, the study dog, or vice versa); three participants underwent this
      intervention on 3 consecutive days. Four participants underwent continuous
      monitoring for 6 hours in their own homes, including two 30-minute periods of
      free interaction with the study dog. MAIN OUTCOME MEASURES: High frequency (HF)
      power values of heart rate variability, which is a measure of parasympathetic
      neural activity. RESULTS: During dog-walking, HF power increased significantly (P
      < 0.01); this increase was sustained throughout each dog walk, and was more
      pronounced during succeeding dog walks. At home, HF power was 1.87 times greater
      when the dog was present, and 1.57 times greater (P < 0.01) than in the walking
      experiment. CONCLUSIONS: Walking a dog has potentially greater health benefits as
      a buffer against stress in senior citizens than walking without a dog; and,
      independent of actually walking, merely patting and talking to a dog also raises
      parasympathetic neural activity. Power spectral analysis of heart rate
      variability shows promise as a non-invasive approach to quantifying
      clinicophysiological research on human health benefits possibly derived from
      interaction with companion animals.

PMID- 16411870
TI  - Television viewing habits associated with obesity risk factors: a survey of
      Melbourne schoolchildren.
AB  - OBJECTIVES: To examine whether children's television viewing may be a useful
      indicator of risk of obesity-promoting versus healthy eating behaviours, low
      level physical activity (PA) and overweight or obesity among children of primary
      school entry and exit ages. DESIGN: Cross-sectional study, stratified by area
      level socioeconomic status. PARTICIPANTS AND SETTING: 1560 children (613 aged 5-6
      years [50% boys], and 947 aged 10-12 years [46% boys]) from 24 primary schools in
      Melbourne, Australia, randomly selected proportionate to school size between 1
      November 2002 and 30 December 2003. MAIN OUTCOME MEASURES: Parents' reports of
      the time their child spends watching television, their participation in organised
      physical activities (PA), and their food intake; each child's measured height and
      weight and their PA levels as assessed by accelerometry for one week. RESULTS:
      After adjusting for the age and sex of child, the parents' level of education,
      clustering by school, and all other health behaviour variables, children who
      watched television for > 2 h/day were significantly more likely than children who
      watched television for < or = 2 h/day to: to have one or more serves/day of high
      energy drinks (adjusted odds ratio [AOR], 2.31; 95% CI, 1.61-3.32), and to have
      one or more serves/day of savoury snacks (AOR, 1.50; 95% CI, 1.04-2.17). They
      were also less likely to have two or more serves/day of fruit (AOR, 0.58; 95% CI,
      0.46-0.74), or to participate in any organised PA (AOR, 0.52; 95% CI, 0.34-0.80).
      CONCLUSIONS: Health practitioners in the primary care setting may find that
      asking whether a child watches television for more than 2 hours daily can be a
      useful indicator of a child's risk of poor diet and low physical activity level.

PMID- 16411871
TI  - Lifestyle factors and risk of dementia: Dubbo Study of the elderly.
AB  - OBJECTIVE: To identify risk factors for dementia in an elderly Australian cohort.
      DESIGN AND SETTING: A longitudinal cohort study conducted in Dubbo, NSW.
      PARTICIPANTS: 2805 men and women aged 60 years and older living in the community
      and initially free of cognitive impairment, first assessed in 1988 and followed
      for 16 years. MAIN OUTCOME MEASURE: Admission to hospital or nursing home with
      any kind of dementia. RESULTS: There were 115 cases of dementia in 1233 men
      (9.3/100) and 170 cases in 1572 women (10.8/100). In a proportional hazards model
      for dementia, any intake of alcohol predicted a 34% lower risk, and daily
      gardening a 36% lower risk. Daily walking predicted a 38% lower risk of dementia
      in men, but there was no significant prediction in women. The lowest tertile of
      peak expiratory flow predicted an 84% higher risk of dementia, the upper tertile
      of depression score predicted a 50% higher risk. CONCLUSION: While excess alcohol
      intake is to be avoided, it appears safe and reasonable to recommend the
      continuation of moderate alcohol intake in those already imbibing, as well as the
      maintenance of physical activity, especially daily gardening, in the hope of
      reducing the incidence of dementia in future years.

PMID- 16411872
TI  - Physical activity for people with cardiovascular disease: recommendations of the
      National Heart Foundation of Australia.
AB  - To provide physical activity recommendations for people with cardiovascular
      disease, an Expert Working Group of the National Heart Foundation of Australia in
      late 2004 reviewed the evidence since the US Surgeon General's Report: physical
      activity and health in 1996. The Expert Working Group recommends that: people
      with established clinically stable cardiovascular disease should aim, over time,
      to achieve 30 minutes or more of moderate intensity physical activity on most, if
      not all, days of the week; less intense and even shorter bouts of activity with
      more rest periods may suffice for those with advanced cardiovascular disease; and
      regular low-to-moderate level resistance activity, initially under the
      supervision of an exercise professional, is encouraged. Benefits from regular
      moderate physical activity for people with cardiovascular disease include
      augmented physiological functioning, lessening of cardiovascular symptoms,
      enhanced quality of life, improved coronary risk profile, superior muscle fitness
      and, for survivors of acute myocardial infarction, lower mortality. The greatest
      potential for benefit is in those people who were least active before beginning
      regular physical activity, and this benefit may be achieved even at relatively
      low levels of physical activity. Medical practitioners should routinely provide
      brief, appropriate advice on physical activity to people with well-compensated,
      clinically stable cardiovascular disease.

PMID- 16411873
TI  - Nutrition problems in an obesogenic environment.
AB  - Many claims about nutrition and weight loss stem from small, short-term studies,
      incorrect interpretations or distortions of evidence. Our knowledge of what
      people eat is poor; difficulties include accurate assessment of consumption, the
      complex composition of foods and individual variations in nutrient
      bioavailability. When advice appears to be ineffective, poor compliance is a
      likely explanation. There is no simple solution to obesity, and no fast way to
      create the energy deficit required for sustainable loss of fat - weight loss
      requires long-term commitment to permanently change eating and exercise habits.
      Valid advice is to reduce overall energy intake, include more vegetables, fruits
      and whole grain products and fewer foods high in saturated fat, sugar and salt.
      While mindful of the need to encourage individuals to make changes, the medical
      profession needs to lead the charge to advocate for changes to our obesogenic
      environment.

PMID- 16411874
TI  - What do we know about men's help-seeking and health service use?
AB  - Men seek help and use health services less frequently than women do. Men's help
      seeking practices and health service use are complex issues involving biological,
      psychological and sociological considerations. Most discussion on men's help
      seeking positions them as reluctant consumers or "behaving badly" with respect to
      their health. Few studies have explored whether health service providers are
      equipped to deal with men's health issues appropriately. The current health
      system appears not to be tailored to meet the health needs of men. Better
      collaboration is required across disciplines, to further investigate men's health
      using both qualitative and quantitative research methods.

PMID- 16411875
TI  - Succimer therapy for congenital lead poisoning from maternal petrol sniffing.
AB  - An infant, born at 35 weeks' gestation to a woman who sniffed petrol, had a cord
      blood lead level eight times the accepted limit. Treatment with oral
      dimercaptosuccinic acid promptly reduced his blood lead levels. To our knowledge,
      this is the first reported case of congenital lead poisoning secondary to
      maternal petrol sniffing. We suggest that at-risk pregnancies should be
      identified, cord blood lead levels tested, and chelation therapy and
      developmental follow-up offered to affected infants.

PMID- 16411876
TI  - Cryptococcal dementia in a patient with sarcoidosis.

PMID- 16411877
TI  - Willingness of general practitioners to participate in enhanced primary care
      discharge care planning.

PMID- 16411878
TI  - Probable transmission of meningococcal disease on a school bus.

PMID- 16411879
TI  - Action is required to reduce kava supply in Arnhem Land . . . again!

PMID- 16411880
TI  - Malignant ascites and bacterial peritonitis.

PMID- 16411881
TI  - Specialty training should not be exclusively hospital-based.

PMID- 16411882
TI  - Severe nocturnal bradycardia with daytime tachycardia in obstructive sleep
      apnoea.

PMID- 16411883
TI  - Problem-based learning: a dissemination success story?

PMID- 16411884
TI  - Intern choices for the first graduates of James Cook University.

PMID- 16411885
TI  - More students and less patients: the squeeze on medical teaching resources.

PMID- 16411886
TI  - Barriers to student access to patients in a group of teaching hospitals.

PMID- 16411887
TI  - Use of prescribed medications in a South Australian community sample.

PMID- 16411888
TI  - Characterization of Schistosoma mansoni Sds homologue, a leucine-rich repeat
      protein that interacts with protein phosphatase type 1 and interrupts a G2/M cell
      cycle checkpoint.
AB  - The suppressor of the dis2 mutant (sds22+) has been shown to be an essential
      regulator in cell division of fission and budding yeast where its deletion causes
      mitotic arrest. Its role seems to take place through the activation of PP1
      (protein phosphatase type 1) in Schizosaccharomyces pombe. In the trematode
      Schistosoma mansoni, we have identified the Sds22 homologue (SmSds), and the PP1
      (SmPP1). We showed by using a GST (glutathione S-transferase) pull-down assay
      that the SmSds gene product interacts with SmPP1 and that the SmSds-SmPP1 complex
      is present in parasite extracts. Furthermore, we observed that SmSds inhibited
      PP1 activity. Functional studies showed that the microinjection of SmSds into
      Xenopus oocytes interacted with the Xenopus PP1 and disrupted the G2/M cell-cycle
      checkpoint by promoting progression to GVBD (germinal vesicle breakdown). Similar
      results showing the appearance of GVBD were observed when oocytes were treated
      with anti-PP1 antibodies. Taken together, these observations suggest that SmSds
      can regulate the cell cycle by binding to PP1.

PMID- 16411889
TI  - Molecular cloning of disintegrins from Cerastes vipera and Macrovipera lebetina
      transmediterranea venom gland cDNA libraries: insight into the evolution of the
      snake venom integrin-inhibition system.
AB  - We report the cloning and sequence analysis of Cerastes vipera and Macrovipera
      lebetina transmediterranea cDNAs coding for short non-RGD (Arg-Gly-Asp)
      disintegrins and for dimeric disintegrin subunits. The mRNAs belong to the short
      coding class, suggesting that these disintegrin mRNAs may be more widely
      distributed than previously thought. Our data also argue for a common ancestry of
      the mRNAs of short disintegrins and those coding for precursors of dimeric
      disintegrin chains. The Macrovipera lebetina transmediterranea dimeric
      disintegrin reported to inhibit the laminin-binding integrins alpha3beta1,
      alpha6beta1 and alpha7beta1 was analysed using a proteomic approach and was shown
      to bear MLD (Met-Leu-Asp) and VGD (Val-Gly-Asp) motifs. The results highlight the
      fact that disintegrins have evolved a restricted panel of integrin-blocking
      sequences that segregate with defined branches of the phylogenetic tree of the
      integrin alpha-chains, providing novel insights into the evolutionary adaptation
      of the snake venom antagonists to the ligand-binding sites of their target
      integrin receptors.

PMID- 16411890
TI  - Crystal structure of inactivated Thermotoga maritima invertase in complex with
      the trisaccharide substrate raffinose.
AB  - Thermotoga maritima invertase (beta-fructosidase), a member of the glycoside
      hydrolase family GH-32, readily releases beta-D-fructose from sucrose, raffinose
      and fructan polymers such as inulin. These carbohydrates represent major carbon
      and energy sources for prokaryotes and eukaryotes. The invertase cleaves beta
      fructopyranosidic linkages by a double-displacement mechanism, which involves a
      nucleophilic aspartate and a catalytic glutamic acid acting as a general
      acid/base. The three-dimensional structure of invertase shows a bimodular enzyme
      with a five bladed beta-propeller catalytic domain linked to a beta-sandwich of
      unknown function. In the present study we report the crystal structure of the
      inactivated invertase in interaction with the natural substrate molecule alpha-D
      galactopyranosyl-(1,6)-alpha-D-glucopyranosyl-beta-D-fructofuranoside (raffinose)
      at 1.87 A (1 A=0.1 nm) resolution. The structural analysis of the complex reveals
      the presence of three binding-subsites, which explains why T. maritima invertase
      exhibits a higher affinity for raffinose than sucrose, but a lower catalytic
      efficiency with raffinose as substrate than with sucrose.

PMID- 16411891
TI  - Neuroendocrine and metabolic effects of adipocyte-derived hormones.
AB  - Obesity is characterized by an increase in adipose tissue mass. Contrary to the
      previous view of adipose tissue as simply an inert tissue devoted to energy
      storage, studies over the past decade have shown that adipose tissue is actively
      involved in regulating physiological processes and participates in disease.
      Adipose tissue secretes factors that exert local and systemic effects. Leptin,
      pro-inflammatory cytokines, resistin and proteins involved in haemodynamic
      regulation and coagulation are increased in obesity while adiponectin is reduced.
      The production of active corticosteroids is also increased in obesity. There is
      now growing evidence that adipocyte secretory factors regulate energy
      homoeostasis, as well as cardiovascular and immune systems. Some adipocyte
      hormones, most notably leptin, act in the brain to influence the neuroendocrine
      axis and energy balance, whereas adiponectin and resistin exert opposing effects
      on glucose and lipids. Understanding the actions of adipocyte hormones will
      provide novel insights into the pathophysiology and treatment of obesity.

PMID- 16411892
TI  - RhoA/Rho-kinase in erectile tissue: mechanisms of disease and therapeutic
      insights.
AB  - Penile erection is a complicated event involving the regulation of corpus
      cavernosal smooth muscle tone. Recently, the small monomeric G-protein RhoA and
      its downstream effector Rho-kinase have been proposed to be important players for
      mediating vasoconstriction in the penis. RhoA/Rho-kinase increases MLC (myosin
      light chain) phosphorylation through inhibition of MLCP (MLC phosphatase) thereby
      increasing Ca2+ sensitivity. This review will outline the RhoA/Rho-kinase
      signalling pathway, including the upstream regulators, guanine nucleotide
      exchange factors, GDP dissociation inhibitors and GTPase-activating proteins. We
      also summarize the current knowledge about the physiological roles of RhoA/Rho
      kinase in both male and female erectile tissues and its aberrations contributing
      to erectile dysfunction in several disease states. Understanding the RhoA/Rho
      kinase signalling pathway in the regulation of erection is important for the
      development of therapeutic interventions for erectile dysfunction.

PMID- 16411893
TI  - Neurotrophin signalling in health and disease.
AB  - Neurotrophins are a unique family of polypeptide growth factors that influence
      the proliferation, differentiation, survival and death of neuronal and non
      neuronal cells. They are essential for the health and well-being of the nervous
      system. NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor), NT-3
      (neurotrophin-3) and NT-4 (neurotrophin-4) also mediate additional higher-order
      activities, such as learning, memory and behaviour, in addition to their
      established functions for cell survival. The effects of neurotrophins depend upon
      their levels of availability, their affinity of binding to transmembrane
      receptors and the downstream signalling cascades that are stimulated after
      receptor activation. Alterations in neurotrophin levels have been implicated in
      neurodegenerative disorders, such as Alzheimer's disease and Huntington's
      disease, as well as psychiatric disorders, including depression and substance
      abuse. Difficulties in administering trophic factors have led to the
      consideration of using small molecules, such as GPCR (G-protein-coupled receptor)
      ligands, which can participate in transactivation events. In this review, we
      consider the signalling pathways activated by neurotrophins in both health and
      disease states.

PMID- 16411894
TI  - Clinical relevance of the neurotrophins and their receptors.
AB  - The neurotrophins are growth factors required by discrete neuronal cell types for
      survival and maintenance, with a broad range of activities in the central and
      peripheral nervous system in the developing and adult mammal. This review
      examines their role in diverse disease states, including Alzheimer's disease,
      depression, pain and asthma. In addition, the role of BDNF (brain-derived
      neurotrophic factor) in synaptic plasticity and memory formation is discussed.
      Unlike the other neurotrophins, BDNF is secreted in an activity-dependent manner
      that allows the highly controlled release required for synaptic regulation.
      Evidence is discussed which shows that sequestration of NGF (nerve growth factor)
      is able to reverse symptoms of inflammatory pain and asthma in animal models.
      Both pain and asthma show an underlying pathophysiology linked to increases in
      endogenous NGF and subsequent NGF-dependent increase in BDNF. Conversely, in
      Alzheimer's disease, there is a role for NGF in the treatment of the disease and
      a recent clinical trial has shown benefit from its exogenous application. In
      addition, reductions in BDNF, and changes in the processing and usage of NGF, are
      evident and it is possible that both NGF and BDNF play a part in the aetiology of
      the disease process. This highly selective choice of functions and disease states
      related to neurotrophin function, although in no way comprehensive, illustrates
      the importance of the neurotrophins in the brain, the peripheral nervous system
      and in non-neuronal tissues. Ways in which the neurotrophins, their receptors or
      agonists/antagonists may act therapeutically are discussed.

PMID- 16411895
TI  - SARS: clinical presentation, transmission, pathogenesis and treatment options.
AB  - SARS (severe acute respiratory syndrome) appeared as the first emerging
      infectious disease of this century. It is fortunate that the culprit virus can be
      grown without much difficulty from a commonly used cell line, allowing an
      unlimited supply of isolates for further molecular studies and leading to the
      development of sensitive diagnostic assays. How the virus has successfully jumped
      the species barrier is still a mystery. The superspreading events that occurred
      within hospital, hotel and high-density housing estate opens a new chapter in the
      mechanisms and routes of virus transmission. The old practice of quarantine
      proved to be still useful in controlling the global outbreak. Despite all the
      available sophisticated tests, alertness with early recognition by healthcare
      workers and prompt isolation of suspected cases is still the most important step
      for containing the spread of the infection. Although the rapidly evolving
      outbreak did not allow the conducting of systematic clinical trails to evaluate
      treatment options, the accumulated experience on managing SARS patients will
      improve the clinical outcome should SARS return. Although SARS led to more than
      700 deaths worldwide, the lessons learnt have prepared healthcare systems
      worldwide to face future emerging and re-emerging infections.

PMID- 16411896
TI  - MITF mediates cAMP-induced protein kinase C-beta expression in human melanocytes.
AB  - The cAMP-dependent pathway up-regulates MITF (microphthalmia-associated
      transcription factor), important for key melanogenic proteins such as tyrosinase,
      TRP-1 (tyrosinase-related protein 1) and TRP-2. We asked whether MITF is also a
      key transcription factor for PKC-beta (protein kinase C-beta), required to
      phosphorylate otherwise inactive tyrosinase. When paired cultures of human
      melanocytes were treated with isobutylmethylxanthine, known to increase
      intracellular cAMP, both protein and mRNA levels of PKC-beta were induced by 24
      h. To determine whether MITF modulates PKC-beta expression, paired cultures of
      human melanocytes were transfected with dn-MITF (dominant-negative MITF) or empty
      control vector. By immunoblotting, PKC-beta protein was reduced by 63+/-3.7%
      within 48 h. Co-transfection of an expression vector for MITF-M, the MITF isoform
      specific for pigment cells, or empty control vector with a full-length PKC-beta
      promoter-CAT (chloramphenicol acetyltransferase) reporter construct (PKC
      beta/CAT) into Cos-7 cells showed >60-fold increase in CAT activity. Melanocytes
      abundantly also expressed MITF-A, as well as the MITF-B and MITF-H isoforms.
      However, in contrast with MITF-M, MITF-A failed to transactivate co-expressed PKC
      beta/CAT or CAT constructs under the control of a full-length tyrosinase
      promoter. Together, these results demonstrate that MITF, specifically MITF-M, is
      a key transcription factor for PKC-beta, linking the PKC- and cAMP-dependent
      pathways in regulation of melanogenesis.

PMID- 16411898
TI  - Probing the importance of hydrogen bonds in the active site of the subtilisin
      nattokinase by site-directed mutagenesis and molecular dynamics simulation.
AB  - Hydrogen bonds occurring in the catalytic triad (Asp32, His64 and Ser221) and the
      oxyanion hole (Asn155) are very important to the catalysis of peptide bond
      hydrolysis by serine proteases. For the subtilisin NK (nattokinase), a bacterial
      serine protease, construction and analysis of a three-dimensional structural
      model suggested that several hydrogen bonds formed by four residues function to
      stabilize the transition state of the hydrolysis reaction. These four residues
      are Ser33, Asp60, Ser62 and Thr220. In order to remove the effect of these
      hydrogen bonds, four mutants (Ser33-->Ala33, Asp60-->Ala60, Ser62-->Ala62, and
      Thr220-->Ala220) were constructed by site-directed mutagenesis. The results of
      enzyme kinetics indicated that removal of these hydrogen bonds increases the free
      energy of the transition state (DeltaDeltaG(T)). We concluded that these hydrogen
      bonds are more important for catalysis than for binding the substrate, because
      removal of these bonds mainly affects the kcat but not the K(m) values. A
      substrate, SUB1 (succinyl-Ala-Ala-Pro-Phe-p-nitroanilide), was used during enzyme
      kinetics experiments. In the present study we have also shown the results of FEP
      (free-energy perturbation) calculations with regard to the binding and catalysis
      reactions for these mutant subtilisins. The calculated difference in FEP also
      suggested that these four residues are more important for catalysis than binding
      of the substrate, and the simulated values compared well with the experimental
      values from enzyme kinetics. The results of MD (molecular dynamics) simulations
      further demonstrated that removal of these hydrogen bonds partially releases
      Asp32, His64 and Asn155 so that the stability of the transition state decreases.
      Another substrate, SUB2 (H-D-Val-Leu-Lys-p-nitroanilide), was used for FEP
      calculations and MD simulations.

PMID- 16411897
TI  - The CD38-independent ADP-ribosyl cyclase from mouse brain synaptosomes: a
      comparative study of neonate and adult brain.
AB  - cADPR (cADP-ribose), a metabolite of NAD+, is known to modulate intracellular
      calcium levels and to be involved in calcium-dependent processes, including
      synaptic transmission, plasticity and neuronal excitability. However, the enzyme
      that is responsible for producing cADPR in the cytoplasm of neural cells, and
      particularly at the synaptic terminals of neurons, remains unknown. In the
      present study, we show that endogenous concentrations of cADPR are much higher in
      embryonic and neonate mouse brain compared with the adult tissue. We also
      demonstrate, by comparing wild-type and Cd38-/- tissues, that brain cADPR content
      is independent of the presence of CD38 (the best characterized mammalian ADP
      ribosyl cyclase) not only in adult but also in developing tissues. We show that
      Cd38-/- synaptosome preparations contain high ADP-ribosyl cyclase activities,
      which are more important in neonates than in adults, in line with the levels of
      endogenous cyclic nucleotide. By using an HPLC method and adapting the cycling
      assay developed initially to study endogenous cADPR, we accurately examined the
      properties of the synaptosomal ADP-ribosyl cyclase. This intracellular enzyme has
      an estimated K(m) for NAD+ of 21 microM, a broad optimal pH at 6.0-7.0, and the
      concentration of free calcium has no major effect on its cADPR production. It
      binds NGD+ (nicotinamide-guanine dinucleotide), which inhibits its NAD+
      metabolizing activities (K(i)=24 microM), despite its incapacity to cyclize this
      analogue. Interestingly, it is fully inhibited by low (micromolar) concentrations
      of zinc. We propose that this novel mammalian ADP-ribosyl cyclase regulates the
      production of cADPR and therefore calcium levels within brain synaptic terminals.
      In addition, this enzyme might be a potential target of neurotoxic Zn2+.

PMID- 16411899
TI  - The effect of body condition on ovarian activity of free ranging tropical jennies
      (Equus asinus).
AB  - Serial ultrasonography was performed on seven jennies to study the effect of
      seasonally fluctuating body condition on ovarian activity during the dry, short
      rainy and long rainy seasons. Kendall Tau correlations and differences of least
      square mean values were compared. A distinct seasonal pattern was observed both
      in body condition and ovarian activity. The mean (+/-SD) Body Condition Score
      (BCS) was lowest during the dry season 2.6 +/- 0.45 when compared with 3.5 +/-
      0.52 and 3.9 +/- 0.58 during the short and long rainy seasons, respectively. The
      mean (+/-SD) number of total follicles was also proportionally low 7.3 +/- 1.6
      during the dry season compared with 9.6 +/- 2.4 and 11.3 +/- 3.3 found during the
      short and the long rainy seasons, respectively. The BCS was positively correlated
      to the total number of follicles and the diameter of the largest follicle during
      all seasons. Periods of increasing BCS and transition between seasons with both
      increasing and decreasing body conditions were strongly correlated to the number
      and size of ovarian follicles. Seasonal fluctuation in the body condition was
      found to be the result of variation in feed resource and ovarian activity was
      also closely following this seasonal pattern. The improvement in body condition
      has generally, a positive impact on emergence of small growing follicles there by
      having influence on the total count of ovarian follicles.

PMID- 16411900
TI  - Fasting-induced changes in ovulation rate, plasma leptin, gonadotropins, GH, IGF
      I and insulin concentrations during oestrus in ewes.
AB  - The aim of this experiment was to study the changes in the hormonal status and
      ovulation rate (OR) evoked by starvation during the follicular phase of the
      oestrous cycle in ewes. To achieve this goal, 12 female crossbreed sheep were
      synchronized and then half of them were fasted from the 12th to the 16th day of
      the oestrous cycle. On the 16th day, analysis of hormones and insulin-like growth
      factor-I (IGF-I) were performed in 10-min intervals. Then, on the 6th day of the
      following oestrous cycle, the OR in all ewes was determined by laparoscopy.
      Fasting reduced significantly (P < 0.05) the OR in ewes (1.25 +/- 0.50) in
      comparison with control (1.75 +/- 0.50). The drop in the OR was coincident with a
      significant (P < 0.001) decrease in the plasma concentration and pulse amplitude
      of leptin (0.29 +/- 0.08 ng/ml versus control 0.53 +/- 0.14 ng/ml), the plasma
      level of luteinizing hormone (LH) (0.19 +/- 0.06 IU/l versus 0.25 +/- 0.09 IU/l
      in control; P < 0.05) and the mean frequency of LH pulses (2.0/h versus 2.5/h in
      control). Fasting resulted also in a significant (P < 0.05) decrease in the
      plasma concentration and pulse amplitude of follicle stimulating hormone (FSH) in
      comparison with the control. Simultaneously, a significant (P < 0.001) drop in
      the IGF-I concentration in the fasted ewes (4.78 +/- 0.91 ng/ml) was found in
      comparison with control (7.63 +/- 1.85 ng/ml). Also the level of insulin were
      significantly (P < 0.001) lower in the fasted (178.99 +/- 39.08 pM/l
      respectively) than in the control sheep (302.66 +/- 49.01 pM/l respectively).
      Meanwhile, a double increase in the growth hormone (GH) pulses frequency and an
      augmentation in its plasma concentrations as a result of starvation was found.
      The obtained results shows that the acute fasting exerts an inhibitory effect on
      the ovulation rate in ewes coincident with suppression in leptin, FSH and LH
      secretion and changes in signalization mediated by GH.

PMID- 16411901
TI  - The distribution of Salmonella serovars in chicken and humans in Lithuania.
AB  - We studied serovars of Salmonella strains isolated from chicken and humans in
      Lithuania over the period from 2000 to 2004. Salmonella strains were isolated and
      identified according to the techniques recommended by International Organisation
      for Standardization (Microbiology of Food and Animal Feeding Stuff--Horizontal
      Method for the Detection of Salmonella, 1998, ISO, Geneva). The per cent of
      infected flocks with Salmonella in separate years was between 1.01% and 3.2%
      during the period of investigation. The contamination rate of broiler legs and
      breasts was higher (2.36% and 4.25%) than that of wings (0.82%). Eighteen
      serovars of Salmonella were identified from the total 300 isolated samples. The
      most prevalent serovars in chicken were Salmonella Enteritidis, Salmonella
      Infantis and Salmonella Typhimurium. Other serovars such as Salmonella
      Montevideo, Salmonella Djugu, Salmonella Isangi, Salmonella Bovismorbificans,
      Salmonella Mbankada, Salmonella Hadar were detected only in one to two samples.
      In general, similar serovars of Salmonella were found in humans and chicken (S.
      Enteritidis and S. Typhimurium), although distinct serovars were found only in
      humans or only in chicken. Analysis of the distribution of Salmonella serovars in
      humans during the seasons of the year indicated that the highest incidence of
      Salmonella was in Summer and in the beginning of Autumn. Analysis of the
      distribution of serovars during the study period indicated that there is a shift
      over time in both humans and chicken.

PMID- 16411902
TI  - Lawsonia intracellularis proliferative enteropathy in a filly.
AB  - Proliferative enteropathy (PE) caused by the obligate intracellular bacterium
      Lawsonia intracellularis is a disease of high economic impact in swine worldwide.
      In most other species the disease occurs as a sporadic infection. This paper
      reports a PE caused by L. intracellularis in a 9-month-old Pura Raza Espanola
      filly with a history of profuse diarrhoea. Pathological lesions consisted of a
      severe proliferative enteritis associated with argyrophilic bacteria in the
      apical cytoplasm of proliferating crypt epithelium. Characteristic PCR products
      confirmed the presumptive diagnosis of L. intracellularis infection. To our
      knowledge this is the first report of PE in a horse in Europe caused by L.
      intracellularis.

PMID- 16411903
TI  - A seminoma in a monorchid guinea fowl (Numida meleagris).
AB  - A case of seminoma in a monorchid adult guinea fowl (Numida meleagris) is
      described. Grossly, a right enlarged testis, which was soft in consistency, and
      white to pale in colour with few spots of haemorrhages was observed.
      Histologically, the testicle revealed diffusely spread sheets of tumour cells.
      The cells were large pleomorphic with eccentrically placed hyperchromic nuclei.
      Mitotic figures were evident. A scanty fibrous stroma, containing lymphocytes and
      histiocytes, separating the groups of tumour cells, along with few areas of
      haemorrhages were observed. Occurrence of seminoma in guinea fowl is unusual and
      hence reported.

PMID- 16411904
TI  - Echium vulgare and Senecio vulgaris poisoning in fighting bulls.
AB  - An unusual case of poisoning by simultaneous ingestion of Echium vulgare L. and
      Senecio vulgaris L. in a herd of Spanish fighting bulls is described. Ten animals
      died from a herd of 700 in an area located in Sierra Norte, Seville (Constantina)
      in Spain. The interest of this case lies both in the breed affected (this is the
      first report on fighting bulls) and the lack of information about bovine
      poisoning by these plants in Spain. Animal samples were obtained from October to
      March. All the dead animals were 1 year old and had grazed at the farm. The
      diagnosis was made by determining the plant species and studying its distribution
      in the pastureland, and also by performing blood analysis of the sick animals in
      addition to an anatomopathological study of the carcasses. Tuberculosis,
      brucellosis, salmonellosis, IBR/BVD and also the presence of aflatoxins in the
      forage were all ruled out.

PMID- 16411905
TI  - Enzootic nasal adenocarcinoma of sheep in Slovenia.
AB  - SUMMARY Clinicopathological and electron microscopical findings of eight cases of
      enzootic nasal adenocarcinoma of sheep, diagnosed solely in one big flock in
      Slovenia between years 2001 and 2003 are described. All affected sheep were
      female, their mean age was 4.5 +/- 1.5 years and they either belonged to the
      Istrian pramenka breed (five sheep) or were crossbreeds (three sheep). Tumours
      that arose from the ethmoid area of the nasal cavity were unilateral in six cases
      (75%) and bilateral in two cases (25%). All tumours were classified as
      adenocarcinomas by histopathological examination and they displayed either a
      combination of tubular and papillary growth or less often solely tubular
      proliferation. No metastases were detected in regional lymph nodes, brain or
      other organs. Electron microscopical studies performed on the reprocessed
      paraffin-embedded tissues revealed the presence of the virus-like particles with
      an average diameter between 70 and 90 nm.

PMID- 16411906
TI  - Equine Culicoides hypersensitivity: evaluation of a skin test and of humoral
      response.
AB  - Intradermal tests were carried out on 18 horses with clinical signs of Culicoides
      hypersensitivity (CHS) and 23 horses without clinical signs of CHS, and sera from
      these horses were analysed by SDS-PAGE and Western blotting (W-B). Intradermal
      injections of 0.1 ml of 25 microg/microl sterile Culicoides extract, 0.1 ml of
      1:10,000 histamine (positive control) and 0.1 ml of physiological saline
      (negative control) were made in the dermis of the middle region of the neck.
      Analysis of reactions indicated that a 1 cm wheal and a skinfold thickness >10%
      at 24 h represented a valid cut-off between horses with and without CHS. In these
      conditions the test, even in winter when clinical signs were absent, had 100%
      sensitivity and specificity. The W-B was performed after running Culicoides
      extract on a 12% polyacrylamide gel. The test revealed the presence of several
      bands with molecular weight ranging from 6 to 200 kDa. In particular, a band of
      65 kDa was predominantly found in hypersensitive horses by using an anti-IgE
      antibody while in normal horses the same band was mainly detected by using an
      anti-IgG antibody. Our results demonstrated that the skin test is a valid
      diagnostic test, with high sensitivity and specificity and that the band of about
      65 kDa probably corresponds to the allergen involved in the pathogenesis of CHS.

PMID- 16411907
TI  - Pharmacokinetics of a lidocaine patch 5% in dogs.
AB  - Lidocaine is increasingly used in transdermal drug delivery systems for different
      pain conditions in human medicine whereby several pharmacokinetic studies have
      demonstrated minimal systemic absorption in men. In the present study, the
      pharmacokinetics of a lidocaine patch 5% was studied in six dogs. In the first
      experiment, one single lidocaine patch was applied for 12 h to the lateral side
      of the thorax after removing the hair either by clipping or by the application of
      a depilatory agent, according to a two-way crossover design. No potential adverse
      effects induced by the patches were observed in either group. In dogs with
      clipped hair, a mean peak plasma lidocaine concentration of 62.94 ng/ml was
      obtained after 10.67 h. In the depilatory group, a mean peak plasma concentration
      of 103.55 ng/ml was reached after 9.27 h. Significant differences in the AUC(0 -
      > infinity), C(max), k(a) and T(1/2a) were noticed between the two groups. No
      significant differences were found for the elimination parameters and for T(max).
      In the second experiment, the patches were applied for 60 h to the clipped skin
      in order to study the absorption kinetics after a prolonged application period.
      There, the mean peak lidocaine plasma concentration was 45.18 ng/ml achieved
      after 24 h and a final concentration of 29.37 ng/ml was obtained at 60 h. In
      conclusion, all dogs tolerated the transdermal lidocaine patch well. The results
      of this study suggest that there is an overall minimal absorption from the
      lidocaine patch. However, the application of a depilatory agent leads to a more
      rapid and increased absorption of lidocaine.

PMID- 16411908
TI  - Seroprevalence of Ornithobacterium rhinotracheale infection in broiler and
      broiler breeder chickens in West Azerbaijan Province, Iran.
AB  - Ornithobacterium rhinotracheale is a pleomorphic Gram-negative rod shaped
      bacterium of the rRNA superfamily V that is associated with respiratory disease
      in poultry. This study was conducted to determine the seroprevalence of O.
      rhinotracheale infection in broiler and broiler breeder chickens in West
      Azerbaijan (Urmia lake region) by using a commercial enzyme-linked immunosorbent
      assay. In this study, 463 serum samples were obtained from 50 broiler flocks and
      472 blood sera from 42 broiler breeder flocks. Results showed that 41 broiler
      flocks (82%) and 39 broiler breeder flocks (92.8%) were positive.
      Ornithobacterium rhinotracheale antibodies were detected in 205 (44.2%) of the
      463 broiler serum samples. Of the 472 blood sera examined from broiler breeder,
      340 (72%) were positive. The results of this study indicated that the prevalence
      of O. rhinotracheale antibodies is high in the broiler and broiler breeder flocks
      in West Azerbaijan.

PMID- 16411909
TI  - Effect of parasitism on the pharmacokinetic disposition of ivermectin in lambs.
AB  - The aim of this study was to investigate the effect of parasitism on plasma
      availability and pharmacokinetic behaviour of ivermectin (IVM) in lambs. Fourteen
      greyface Suffolk lambs (26.8 +/- 2.2 kg body weight) were selected for this
      study. Seven pairs of lambs were allocated into two groups in order to obtain an
      approximately even distribution. Group I (non-parasitized) was pre-treated by
      three repeated administrations of 5 mg/kg of fenbendazole (Panacur), in order to
      maintain a parasite-free condition. The lambs in group II (parasitized) did not
      receive any anthelmintic treatment and the natural infection was sustained by an
      oral inoculation of infective stages of nematode parasites. After the 85-day pre
      treatment period both groups of animals were treated with IVM (200 microg/kg,
      Ivomec) by subcutaneous injection in the shoulder area. Both groups of animals
      were maintained under similar conditions of feeding and management. Blood samples
      were collected by jugular puncture at different times between 0.5 h and 25 days
      post-treatment. After plasma extraction and derivatization, samples were analysed
      by high-performance liquid chromatography with fluorescence detection. A
      computerized kinetic analysis was performed and data were compared using the
      unpaired Student's t-test. The parent molecule was detected in plasma between 30
      min and either 12 (parasitized) or 20 (no parasitized) days post-IVM treatment.
      The area under the curve values of the parasitized group (75.2 +/- 15.5 ng x
      d/ml) were significantly lower that those observed in the parasite-free group
      (134.3 +/- 15.7 ng x d/ml). The mean residence time (MRT) of the parasitized
      group (2.93 +/- 0.16 days) was significantly lower than the MRT of healthy group
      (3.93 +/- 0.29 days). The results of this study have shown that a change in body
      condition followed by a parasitic infection is associated with significant
      changes in plasma disposition of IVM when it is administered subcutaneously to
      parasitized lambs. Therefore, variations in the condition induced by parasitism
      should be considered when these anthelmintics are used for treating parasitized
      animals.

PMID- 16411910
TI  - Effects of curcumin on tumour necrosis factor-alpha and interleukin-6 in the late
      phase of experimental acute pancreatitis.
AB  - Summary Inflammatory cytokines have been demonstrated to play an important role
      in the induction and severity of acute pancreatitis (AP) in the recent studies.
      The aim of this study was to investigate the effects of curcumin on inflammatory
      cytokines, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in
      the late phase of AP. The study was conducted on 40 male Wistar Albino rats. The
      animals were divided randomly into four equal groups. AP was induced by the
      infusion of 3% sodium taurocholate into the biliopancreatic duct (in groups I and
      II). Starting on day 20 prior to the induction of AP, rats in group I received
      daily dose of 100 mg/kg of curcumin, dissolved in 9% ethanol via an intragastric
      tube. The same procedure was repeated for 6 days following the onset of AP. Group
      III was infused only on saline solution. Group IV (curcumin control group)
      received 9% ethanol via an intragastric tube, during the experimental period
      (totally 26 days). All the animals were sacrificed on day 6 after the collection
      of blood samples and serum TNF-alpha and IL-6 levels were determined. Tissue
      samples were taken from pancreas, mesenteric lymph nodes, liver, lungs, spleen
      and the kidneys for histopathological evaluation. Serum TNF-alpha and IL-6 levels
      in the group, which received curcumin (group I), were determined to be
      significantly lower than those of the untreated group (group II) (P<0.05). No
      statistically significant difference was detected in terms of total
      histopathological scores in the treatment group versus untreated group. Curcumin
      has been shown to markedly reduce serum TNF-alpha and IL-6 levels in the late
      phase of AP, but failed in the prevention of tissue injury.

PMID- 16411912
TI  - Under the microscope: Arcobacter.
AB  - This review describes characteristics of the genus Arcobacter. Unlike its close
      phenotypically related neighbour Campylobacter, Arcobacter is not currently a
      major public health concern, but is considered as an emerging human pathogen, and
      is of significance towards animal health. This review focuses on the public
      health significance, culturing and typing, reservoirs, and antimicrobial studies
      of Arcobacter. Collectively, increasing knowledge in these areas will help to
      develop measures, which can be used to control this emerging pathogen.

PMID- 16411913
TI  - Detection and quantification of Listeria monocytogenes by 5'-nuclease polymerase
      chain reaction targeting the actA gene.
AB  - AIMS: The aim of this study was to develop a 5'-nuclease polymerase chain
      reaction (PCR) for the rapid detection and quantification of Listeria
      monocytogenes. METHODS AND RESULTS: Specific primers and a fluorogenic probe were
      designed, which target a specific sequence of the actA gene encoding for a
      protein involved in the actin filament assembly. The PCR system was highly
      sensitive and specific for L. monocytogenes (inclusivity, 100%; exclusivity,
      100%), which was determined using 46 L. monocytogenes and 28 non-L. monocytogenes
      strains. Detection limits of 10(4) cfu ml(-1) after 35 cycles and 10(2) cfu ml(
      1) after 45 cycles were achieved by PCR in both real-time and end-point
      fluorescence measurement modes. Linear calibration lines were obtained in the
      range from 10(2) to 10(9) cfu ml(-1) for three L. monocytogenes strains in real
      time PCR with 45 cycles. CONCLUSIONS: The developed 5'-nuclease PCR of the actA
      gene provides a new target for the rapid detection and quantification of L.
      monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: In conjunction with
      enrichment or with an appropriate quantitative sample preparation technique, the
      method is suitable for food safety applications.

PMID- 16411914
TI  - The probiotic bacterium Lactobacillus plantarum species 299 reduces intestinal
      permeability in experimental biliary obstruction.
AB  - AIMS: Extrahepatic biliary obstruction is associated with the failure of
      intestinal barrier function, allowing bacteria and other substances from the
      intestine to enter the circulation and initiate a systemic inflammatory response,
      causing impairment of organ function. Probiotic bacteria have been shown to have
      beneficial effects on intestinal barrier function in other conditions, but their
      effects have never been studied in biliary obstruction. METHODS AND RESULTS: This
      study examined the effects of enteral administration of Lactobacillus plantarum
      species 299 (LP299) in oatmeal fibre compared with sterile oatmeal fibre in water
      or water alone in an animal model of biliary obstruction. Administration of LP299
      was associated with reduced intestinal permeability compared with sterile oatmeal
      alone (0.262 +/- 0.105%vs 0.537 +/- 0.037%, P=0.019, percentage excretion of
      (14)Carbon), but there was no evidence of reduced endotoxin exposure or blunting
      of the systemic inflammatory response. Animals receiving sterile oatmeal fibre
      alone also failed to develop the hyperpermeability after biliary obstruction seen
      in animals receiving water only (0.512+/- 0.05%vs 0.788 +/- 0.18%), suggesting
      that oatmeal itself may have some beneficial effects on intestinal barrier
      function. CONCLUSION: Enteral administration of the probiotic bacterium LP299
      reduces intestinal hyperpermeability associated with experimental biliary
      obstruction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insight to
      direct further work into the modulation of intestinal barrier function by
      probiotic bacteria.

PMID- 16411915
TI  - Experimental use of a new surface acoustic wave sensor for the rapid
      identification of bacteria and yeasts.
AB  - AIMS: Use of an electronic nose (zNose(TM)) to discriminate between volatile
      organic molecules delivered during bacterial/fungal growth on agar and in broth
      media. METHODS AND RESULTS: Cultures of bacteria (Klebsiella pneumoniae,
      Pseudomonas aeruginosa, Escherichia coli) and yeasts (two Candida albicans
      strains) were grown on agar and in broth media and incubated for 24 h at 37
      degrees C. Headspace samples from microbial cultures were analysed by the
      zNose(TM), a fast gas chromatography-surface acoustic wave detector. Olfactory
      images of volatile production patterns were observed to be different for the
      various species tested after 24 h. Moreover, some strains (two K. pneumoniae, two
      C. albicans) did not show changes in volatile production patterns within our
      species. CONCLUSIONS: Our experiments demonstrate that the electronic nose system
      can recognize volatile production patterns of pathogens at species level.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Our results, although preliminary, promise
      exciting challenges for microbial diagnostics.

PMID- 16411916
TI  - Coagulase gene polymorphism of Staphylococcus aureus isolated from goat mastitis
      in Brazilian dairy herds.
AB  - AIMS: To investigate the coagulase gene polymorphism of Staphylococcus aureus
      isolated from mastitic goat's milk. METHODS AND RESULTS: A typing procedure based
      on coagulase gene polymorphism was used to discriminate S. aureus isolated from
      goat mastitis. Thirty-six strains collected from goats belonging to herds from
      northern Ceara State and Serrana region of Rio de Janeiro State were analysed.
      Based on restriction fragment length polymorphism of 3' end coagulase gene, the
      goat strains were grouped into 11 types. In northern Ceara herds, the predominant
      type was found in 60% of the strains, while in the Serrana region herds the two
      most common accounting for 62.5% of the strains. CONCLUSIONS: The analysis of the
      coa gene proved to be useful for typing S. aureus from goat mastitis. Although
      the results showed that goats from the studied regions were infected by S. aureus
      strains harbouring more than one coagulase genotype, only one or two types
      predominated. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of the
      prevalent strains within a herd or region is a necessity. The important virulence
      factors could be identified in such strains and this information can then be used
      as a specific base to develop S. aureus mastitis control measures.

PMID- 16411917
TI  - Biotransformation of p-coumaric acid by Paecilomyces variotii.
AB  - AIMS: To investigate the biotransformation of p-coumaric acid into p
      hydroxybenzoic acid (p-HBA) by Paecilomyces variotii Bainier MTCC 6581. METHODS
      AND RESULTS: As a result of p-coumaric acid degradation by P. variotii, three
      phenolic metabolites, p-hydroxybenzaldehyde (p-HBAld), p-HBA and protocatechuic
      acid were formed. These phenolics were detected using TLC and HPLC. The identity
      of p-HBA and p-HBAld was further confirmed by mass spectrometry. Various analyses
      showed that 10.0 mmol l(-1) concentration of p-coumaric acid produced a maximum
      amount of p-hydroxybenzoic acid, 200 mg l(-1), into the medium at 37 degrees C
      with high-density cultures. CONCLUSIONS: A catabolic pathway of p-coumaric acid
      by the fungus P. variotii is suggested for the first time. During the process of
      p-coumaric acid degradation, p-HBA accumulated in the medium as the major
      degradation product. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial degradation
      of cinnamic acid and hydroxycinnamic acid has continued to be the focus of
      intensive study. The main goal was to identify the microbial species capable of
      converting these substances into commercially value-added products such as
      benzoic acid derivatives or aromatic aldehydes.

PMID- 16411918
TI  - Fungi and ochratoxin A detected in healthy grapes for wine production.
AB  - AIMS: The mycoflora of healthy grapes (i.e. without visible symptoms of rot) for
      wine production in Portuguese wine-making regions was assessed and its potential
      for ochratoxin A (OTA) production evaluated. The OTA content of grapes was also
      determined. METHODS AND RESULTS: A total of 386 fungal strains were isolated by
      plating methods. The most frequent genera found in grapes were non-ochratoxigenic
      species: Cladosporium (28%), Penicillium (24%), Botrytis (13%) and Aspergillus
      (9%). Two OTA-producing strains were isolated, belonging to the species
      Aspergillus carbonarius and Aspergillus ochraceus. OTA was detected in three of
      four grape samples, up to 116 ng l(-1). CONCLUSIONS: OTA is being produced in
      healthy berries by Aspergillus species, namely A. carbonarius, at levels below
      the maximum recommended limit of 2,000 ng l(-1) in wine. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The OTA concentration detected in healthy Portuguese grapes does
      not represent a risk to wine regarding the legal limit established.

PMID- 16411919
TI  - Detection of phages carrying the Shiga toxin 1 and 2 genes in waste water and
      river water samples.
AB  - AIMS: To evaluate the occurrence and abundance of phages that carry the stx(1)
      and stx(2) gene in water samples of different quality. METHODS AND RESULTS:
      Phages growing on the Shiga toxin-negative Escherichia coli O157:H7 (ATCC 43,888)
      strain were enumerated by a plaque assay in concentrated raw and treated waste
      water samples and river water samples. Plaques were investigated for the presence
      of stx(1) and stx(2) genes by a multiplex/nested PCR procedure. An overall number
      of 805 plaques were tested for the presence of stx-carrying phages. Stx genes
      could be demonstrated in 2% (stx(1)) and 16% (stx(2)) of the plaques. Stx-phages
      were eliminated with approximately the same efficiency in comparison with somatic
      coliphages during the waste water treatment process. CONCLUSIONS: Due to the low
      numbers of phages carrying the stx genes 1 and 2 in treated waste water and river
      water, the dilution and inactivation of host bacteria and the unsuitable
      conditions for the transduction of host organisms in aquatic environments, it is
      difficult to derive from the data the direct evidence for a public health
      problem. SIGNIFICANCE AND IMPACT OF THE STUDY: The results show the quantitative
      occurrence of stx-carrying phages in waste and river water and confirm the
      frequent circulation of these viruses in the aquatic environment.

PMID- 16411920
TI  - Evidence for quorum sensing in Clostridium botulinum 56A.
AB  - AIMS: Experiments were designed to detect quorum-sensing signals produced by
      Clostridium botulinum. METHODS AND RESULTS: Clostridium botulinum 56A cell-free
      supernatants obtained at the end of lag phase, the mid-exponential phase and
      early stationary phase of growth were assayed for bioluminescence in the Vibrio
      harveyi quorum-sensing assay system. Twelve and 16-h culture supernatants induced
      bioluminescence in the auto-inducer 2 (AI-2) but not the auto-inducer 1 (AI-1)
      assay. Intra-species quorum sensing was also assayed as the ability of the
      supernatants to promote spore germination and outgrowth in a microtitre plate
      system. Spore populations exposed to C. botulinum supernatant from the end of lag
      phase became positive for growth sooner than controls. CONCLUSIONS: The influence
      of cell-free supernatant on ungerminated spores and detection of bioluminescence
      in the AI-2 assay are evidence for a signalling molecule(s) and provide a first
      step in characterizing C. botulinum quorum sensing. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study suggests that spores do not behave independently of each
      other and may explain the inocula size effects observed in challenge studies.
      Whether AI-2 production in C. botulinum serves as an inter-species signal or as a
      detoxification mechanism remains to be determined.

PMID- 16411921
TI  - An enzyme-linked immunosorbent assay for monitoring of Aspergillus ochraceus
      growth in coffee powder, chilli powder and poultry feed.
AB  - AIMS: The work was carried out to develop an immunoassay for estimation of
      Aspergillus ochraceus biomass on solid substrate. METHODS AND RESULTS: An
      indirect noncompetitive enzyme-linked immunosorbent assay (ELISA) was developed
      for determination of fungal biomass in food commodities using antibody raised
      against A. ochraceus mycelial antigen. The sensitivity of the assay was linear in
      the range of 10-160 microg fungal biomass per millilitre extract of coffee
      (R(2)=0.989), poultry feed (R(2)=0.987) and chilli (R(2)=0.989). The growth of A.
      ochraceus in the food commodities like chilli, coffee beans and poultry feed,
      under the influence of two levels of moisture (20% and 30%) were monitored by the
      ELISA. The maximum fungal colonization was observed in poultry feed (9.8 and 11.8
      mg g(-1)) followed by coffee beans (6.8 and 11.3 mg g(-1)) and chilli (5.1 and
      6.3 mg g(-1)) at 20% and 30% moisture after 20 days of incubation. Similarly the
      fungus produced maximum ochratoxin A in poultry feed (25 and 120 microg g(-1))
      followed by coffee beans (8 and 24 microg g(-1)) and chilli (0.2 and 0.45 microg
      g(-1)) at 20% and 30% moisture after 20 days of incubation. CONCLUSIONS: The
      method can be used for quantitative estimation of fungal biomass and comparison
      of fungal colonization in food substrates varying in composition. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The method can be adapted for studying the fungal
      colonization in different solid substrates under different culture condition. The
      method is sensitive to mould colonization of >or=0.02% (w/w) and can be used for
      early detection of specific fungal infestation in food commodities.

PMID- 16411922
TI  - Secretion of human epidermal growth factor by Corynebacterium glutamicum.
AB  - AIMS: To examine the secretion of human epidermal growth factor (hEGF) by
      Corynebacterium glutamicum. METHODS AND RESULTS: We recently showed that a novel
      protein-secretion system in C. glutamicum could produce Streptomyces mobaraensis
      transglutaminase. In the present study, the industrially important protein hEGF
      was secreted into the culture medium in a fully active form by C. glutamicum and
      accumulated at a rate of up to 156 mg l(-1) day(-1). CONCLUSIONS: These results
      demonstrated that the hEGF protein could be secreted in an active form by C.
      glutamicum. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data confirmed that the
      pharmaceutically important human protein hEGF could be efficiently secreted in an
      active form by the C. glutamicum protein-expression system. Moreover, we
      demonstrated that this bacterium has potential as a host for the industrial-scale
      production of human proteins.

PMID- 16411923
TI  - Differentiation of faecal Escherichia coli from humans and animals by multiple
      antibiotic resistance analysis.
AB  - AIMS: Multiple antibiotic resistance (MAR) was performed on 128 Escherichia coli
      isolates, recovered from faecal samples of humans and animals (cattle, goat,
      sheep) to determine and compare their antibiotic resistance patterns and to
      evaluate them statistically in order to specify the source of the faecal
      material. METHODS AND RESULTS: Disk diffusion method was applied with a selection
      of antibiotics. Statistical approach was performed with hierarchical cluster
      analysis (CA), discriminant analysis (DA) and principal component analysis.
      Comparing human and animal isolates there was significant difference in levels of
      resistance to all antibiotics tested (P<0.05) with 46 and 24 distinct resistance
      patterns for human and animal isolates respectively. CA and DA separated human
      and animal isolates with a high average rate of correct classification (99.2%),
      when all animal isolates were pooled together. CONCLUSIONS: MAR analysis compared
      with appropriate statistical evaluation may provide a useful tool for
      differentiating the human or animal origin of E. coli isolates derived from
      environmental samples. Subsequently, determination of the source of faecal
      pollution becomes possible. SIGNIFICANCE AND IMPACT OF THE STUDY: Determining the
      source of faecal pollution enables the prediction of possible risk for public
      health and the application of appropriate management plans for prevention of
      further contamination.

PMID- 16411924
TI  - Effect of osmotic stress on the derepression of invertase synthesis in
      nonconventional yeasts.
AB  - AIMS: The aim of this study was to analyse the effect of osmotic stress on the
      biosynthesis of invertase enzyme in nonconventional yeasts. METHODS AND RESULTS:
      Invertase activities of the nonconventional yeast species belonging to
      Kluyveromyces, Schwanniomyces and Pichia genus were measured either in the
      presence or in the absence of various amounts of NaCl. The effect of hyperosmotic
      stress on the glucose consumption of Saccharomyces cerevisiae and Pichia anomala
      were also compared. Like S. cerevisiae, derepression of invertase synthesis in
      Kluyveromyces lactis, Schwanniomyces occidentalis and Pichia jadinii is inhibited
      by hyperosmotic stress. However, derepression of invertase synthesis in P.
      anomala is not affected by hyperosmotic stress. In addition, low levels of
      osmotic stress activated invertase synthesis three- to fourfold in P. anomala and
      K. lactis. CONCLUSIONS: This study shows that low levels of osmotic stress
      induces the invertase synthesis at very high levels in P. anomala and K. lactis.
      Glucose consumption was not influenced at significant levels by the hyperosmotic
      stress in P. anomala. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the
      activation of invertase synthesis by low levels of osmotic stress in P. anomala
      and K. lactis.

PMID- 16411925
TI  - Scaling the paths of resistance.

PMID- 16411926
TI  - Grain filling of cereals under soil drying.
AB  - Monocarpic plants require the initiation of whole-plant senescence to remobilize
      and transfer assimilates pre-stored in vegetative tissues to grains. Delayed
      whole-plant senescence caused by either heavy use of nitrogen fertilizer or
      adoption of lodging-resistant cultivars/hybrids that remain green when the grains
      are due to ripen results in a low harvest index with much nonstructural
      carbohydrate (NSC) left in the straw. Usually, water stress during the grain
      filling period induces early senescence, reduces photosynthesis, and shortens the
      grain-filling period; however, it increases the remobilization of NSC from the
      vegetative tissues to the grain. If mild soil drying is properly controlled
      during the later grain-filling period in rice (Oryza sativa) and wheat (Triticum
      aestivum), it can enhance whole-plant senescence, lead to faster and better
      remobilization of carbon from vegetative tissues to grains, and accelerate the
      grain-filling rate. In cases where plant senescence is unfavorably delayed, such
      as by heavy use of nitrogen and the introduction of hybrids with strong
      heterosis, the gain from the enhanced remobilization and accelerated grain
      filling rate can outweigh the loss of reduced photosynthesis and the shortened
      grain-filling period, leading to an increased grain yield, better harvest index
      and higher water-use efficiency.

PMID- 16411927
TI  - Flexible stigma presentation assists context-dependent pollination in a wild
      columbine.
AB  - Stigma presentation has received much less attention than pollen presentation.
      Investigation of the various forms of stigma presentation may reveal previously
      undescribed reproductive mechanisms in plants. Here we investigated stigma
      presentation in the spring-flowering herb Aquilegia yabeana, whose linear stigma
      gradually develops over the lifetime of the flower. The degree of stigma
      development and recurvature are influenced by the timing of pollen deposition,
      apparently to favor cross-pollination. In this species, autogamous self
      pollination was found to occur in the middle of the receptive period of the
      stigma if prior cross-pollination did not occur. However, because later-arriving
      cross-pollen was deposited closer to the ovary, it reached the base of the style
      before self-pollen which had been deposited earlier. Flexible stigma presentation
      helps the flower to maximize pollen resources under unreliable pollination
      conditions, taking advantage of both selfing and outcrossing. This is the first
      description of stigma development regulated by pollen deposition in a wild plant.

PMID- 16411928
TI  - Cotyledon damage at the seedling stage affects growth and flowering potential in
      mature plants.
AB  - Seedling herbivory is an important selective filter influencing patterns of plant
      community composition. Nevertheless, while many of the mechanisms governing
      seedling selection by herbivores are well established, the effects of tissue loss
      at the seedling stage on subsequent plant development are poorly understood. Here
      we examined how the removal of 50 or approximately 100% of cotyledon area from 7
      d-old chalk grassland seedlings affected subsequent plant growth and flowering
      over a 100-d period. Cotyledon damage had a significant effect on growth during
      the establishment phase for six of the nine species. For two species, significant
      effects on plant growth were manifest in 100-d-old plants. Of the five species
      that flowered, three developed fewer inflorescences or flowered later as a
      consequence of cotyledon damage suffered as a seedling. Our results show that, in
      addition to the direct effect of herbivory on seedling mortality, more subtle
      sublethal effects may also influence plant establishment. Reduced growth as a
      result of cotyledon damage may have implications for plant competition during the
      establishment phase, and on subsequent reproductive success at maturity.

PMID- 16411929
TI  - A mutation in the herbicide target site acetohydroxyacid synthase produces
      morphological and structural alterations and reduces fitness in Amaranthus
      powellii.
AB  - We investigated the effect of a herbicide resistance-conferring mutation on
      fitness in Amaranthus powellii. Morphological and histological observations were
      made. Growth and leaf appearance were recorded for six resistant and six
      susceptible populations. The competitiveness of a susceptible population was
      compared with that of a resistant population using a replacement series
      experiment. Leaves of the resistant plants were distorted and much smaller than
      those of susceptible plants. Additionally, they exhibited an abnormal
      morphological and structural pattern consisting of a mosaic of heterogeneous
      areas in the same leaf blade. The roots and stems had similar structures in
      susceptible and resistant plants, but the former were up to four times more
      developed. The resistant plants were slower to develop and produced 67% less
      biomass and 58% lower leaf area than susceptible plants. Under competitive
      conditions, one susceptible population outperformed one resistant population by 7
      15 times. The Trp(574)Leu acetohydroxyacid synthase (AHAS) mutation appears to
      have considerable pleiotropic effects on the early growth and development of the
      plants which, in competitive conditions, greatly reduce fitness.

PMID- 16411930
TI  - Combined agronomic and physiological aspects of nitrogen management in wheat
      highlight a central role for glutamine synthetase.
AB  - In wheat the period of grain filling is characterized by a transition for all
      vegetative organs from sink to source status. To study this transition, the
      progression of physiological markers and enzyme activities representative of
      nitrogen metabolism was monitored from the vegetative stage to maturity in
      different leaf stages and stem sections of two wheat (Triticum aestivum)
      cultivars grown at high and low levels of N fertilization. In the two cultivars
      examined, we found a general decrease of the metabolic and enzyme markers
      occurred during leaf ageing, and that this decrease was enhanced when plants were
      N-limited. Both correlation studies and principal components analysis (PCA)
      showed that there was a strong relationship among total N, chlorophyll, soluble
      protein, ammonium, amino acids and glutamine synthetase (GS) activity. The use of
      a marker such as GS activity to predict the N status of wheat, as a function of
      both plant development and N availability, is discussed with the aim of selecting
      wheat genotypes with better N-use efficiency.

PMID- 16411932
TI  - The response of leaf morphology to irradiance depends on altitude of origin in
      Nothofagus cunninghamii.
AB  - Leaf morphology varies reliably with increasing altitude in many species, and
      this is generally considered to be related to temperature. Changes in irradiance
      with elevation may confound any relationships between a morphological character
      and altitude, particularly if altitude of origin affects the response to
      irradiance. Here we describe the interaction between irradiance and altitude of
      origin on leaf morphology of Southern beech, Nothofagus cunninghamii. Cuttings
      from each of four altitudes were grown in a glasshouse under full sunlight or 50%
      shade, and leaf morphology was related to irradiance, altitude of origin and
      accession. There was a significant interaction between irradiance and altitude of
      origin for leaf length, width, thickness, area, weight, specific leaf area and
      stomatal density. There was no effect of altitude on leaf length to width ratio
      or stomatal index, nor was there an interaction between irradiance and altitude
      of origin for these variables. These results show that the altitude of origin of
      a plant has an overriding impact on the leaf morphological response to
      irradiance. This must be considered in climatic reconstructions.

PMID- 16411931
TI  - Convergent tapering of xylem conduits in different woody species.
AB  - A recent theoretical model (the West, Brown and Enquist, WBE model) hypothesized
      that plants have evolved a network of xylem conduits with a tapered structure
      (narrower conduits distally) which should minimize the cost of water transport
      from roots to leaves. Specific measurements are required to test the model
      predictions. We sampled both angiosperms and gymnosperms (50 trees) growing in
      different environments with heights ranging from 0.5 to 44.4 m, measuring
      variations of the xylem-conduit diameter from tree top to stem base. In all trees
      measured, mean hydraulically weighted conduit diameters (Dh) at the tree top were
      narrower than those at the stem base. In actively growing trees, the longitudinal
      variation of Dh showed a degree of tapering in agreement with WBE predictions,
      while trees close to their maximum height showed slightly lower conduit tapering.
      Comparing different species, a very good correlation was observed between degree
      of xylem tapering and tree height (r2 = 0.88; P < 0.0001) independently of any
      other variable (age, site, altitude, etc.). As predicted by WBE, sampled trees
      seemed to converge towards similar xylem conduit tapering. However, trees
      approaching their maximum height had a nonoptimal tapering which appeared
      insufficient to compensate for the progressive increase in tree height.

PMID- 16411933
TI  - Radial growth of Pinus sylvestris growing on alluvial terraces is sensitive to
      water-level fluctuations.
AB  - Along the Alpine river Lech (Tyrol, Austria), poorly grown Scots pine (Pinus
      sylvestris) stands dominate on dry alluvial terraces, which are made up of coarse
      calcareous gravel. Here we evaluated the impact of environmental factors, such as
      precipitation, temperature and water table, on annual variability of radial
      growth. Tree-ring chronologies from six stands comprising different age classes
      were developed by extracting two core samples from more than 15 trees per plot.
      Pearson correlations were applied to determine the influence of environmental
      factors. Close inverse correlations (r2 > 0.35) between maximum water table
      during the growing period and annual increments of adult stands indicated that
      water surplus in the rooting zone was the primary growth-limiting factor. Drought
      stress reduced growth only in some extremely dry years. Results provide evidence
      that dominance of P. sylvestris on gravelly alluvial terraces is caused not only
      by tolerance of soil dryness and nutrient deficiency, as previously assumed, but
      also by a dynamic multilayered root system which allows adaptation to highly
      variable soil-moisture conditions.

PMID- 16411934
TI  - Irradiance, temperature and rainfall influence leaf dark respiration in woody
      plants: evidence from comparisons across 20 sites.
AB  - Leaf dark respiration (R) is one of the most fundamental physiological processes
      in plants and is a major component of terrestrial CO2 input to the atmosphere.
      Still, it is unclear how predictably species vary in R along broad climate
      gradients. Data for R and other key leaf traits were compiled for 208 woody
      species from 20 sites around the world. We quantified relationships between R and
      site climate, and climate-related variation in relationships between R and other
      leaf traits. Species at higher-irradiance sites had higher mean R at a given leaf
      N concentration, specific leaf area (SLA), photosynthetic capacity (Amass) or
      leaf lifespan than species at lower-irradiance sites. Species at lower-rainfall
      sites had higher mean R at a given SLA or Amass than species at higher-rainfall
      sites. On average, estimated field rates of R were higher at warmer sites, while
      no trend with site temperature was seen when R was adjusted to a standard
      measurement temperature. Our findings should prove useful for modelling plant
      nutrient and carbon budgets, and for modelling vegetation shifts with climate
      change.

PMID- 16411935
TI  - Effects of intraleaf variations in carbonic anhydrase activity and gas exchange
      on leaf C18OO isoflux in Zea mays.
AB  - Variation in the C18OO content of atmospheric CO2 (delta18Oa) can be used to
      distinguish photosynthesis from soil respiration, which is based on carbonic
      anhydrase (CA)-catalyzed 18O exchange between CO2 and 18O-enriched leaf water
      (delta18Ow). Here we tested the hypothesis that mean leaf delta18Ow and
      assimilation rates can be used to estimate whole-leaf C18OO flux (isoflux),
      ignoring intraleaf variations in CA activity and gas exchange parameters. We
      observed variations in CA activity along the leaf (> 30% decline from the leaf
      center toward the leaf ends), which were only partially correlated to those in
      delta18Ow (7 to 21 per thousand), delta18O and delta13C of leaf organic matter
      (25 to 30 per thousand and -12.8 to -13.2 per thousand, respectively), and
      substomatal CO2 concentrations (intercellular CO2 concentrations, c(i), at the
      leaf center were approximately 40% of those at the leaf tip). The combined effect
      of these variations produced a leaf-integrated isoflux that was different from
      that predicted based on bulk leaf values. However, because of canceling effects
      among the influencing parameters, isoflux overestimations were only approximately
      10%. Conversely, use of measured parameters from a leaf segment could produce
      large errors in predicting leaf-integrated C18OO fluxes.

PMID- 16411936
TI  - The lichen-forming ascomycete Evernia mesomorpha associates with multiple
      genotypes of Trebouxia jamesii.
AB  - The epiphyte Evernia mesomorpha forms a lichen association with green algae in
      the genus Trebouxia. Little is known about the population structure of E.
      mesomorpha. Here, population structure of the algal and fungal symbionts was
      examined for 290 lichen thalli on 29 jack pine (Pinus banksiana) trees in
      Manitoba. Through phylogenetic analysis of internal transcribed spacer (ITS)
      nuclear ribosomal DNA (rDNA) sequences, five algal genotypes were detected that
      were nested within T. jamesii. Two fungal genotypes were detected that formed a
      clade with two other Evernia species. The genus Evernia was paraphyletic with E.
      prunastri, sister to Parmelia saxatilis. Restriction fragment length polymorphism
      (RFLP) of ITS rDNA showed multiple algal genotypes in 45% of the 290 lichen
      thalli collected, whereas all thalli only contained one fungal genotype. Low
      population subdivision of algal and fungal genotypes among trees suggested that
      the algal symbiont was being dispersed in the lichen soredium. Low fungal
      specificity for multiple algal genotypes and a hypothesized algal switch may be
      important life history strategies for E. mesomorpha to adapt to changing
      environmental conditions.

PMID- 16411937
TI  - Ectomycorrhizal ecology under primary succession on coastal sand dunes:
      interactions involving Pinus contorta, suilloid fungi and deer.
AB  - Ectomycorrhizal fungi (EMF) are critical for pine establishment under primary
      succession. The species of EMF supporting primary successional pine seedlings on
      coastal sand dunes and mechanisms for their establishment were investigated.
      Fungi were identified from ectomycorrhizal roots using molecular techniques.
      Field seedlings were collected from forested and nonforested zones. Laboratory
      seedlings were grown in soils collected from the same zones, and in sterile soils
      inoculated with fresh and 1-yr-old dry deer fecal pellets. Suilloid fungi were
      frequently observed on all seedlings. A diverse group of fungi was available to
      seedlings in forested zones. A less diverse group of fungi was available to field
      seedlings in nonforested zones and all laboratory bioassay seedlings. Deer fecal
      inoculant yielded an average of two EMF per seedling. Both Suillus and Rhizopogon
      species dominated seedlings inoculated with fresh deer feces, but only Rhizopogon
      species dominated seedlings inoculated with 1-yr-old feces. Suilloid fungi are
      dispersed by deer, produce resistant spore banks and are the principle fungi
      supporting seedlings on the sand dunes.

PMID- 16411938
TI  - Sebacinales form ectendomycorrhizas with Cavendishia nobilis, a member of the
      Andean clade of Ericaceae, in the mountain rain forest of southern Ecuador.
AB  - Cavendishia nobilis var. capitata is an endemic member of the Ericaceae growing
      as a hemiepiphyte in the tropical mountain rain forest of southern Ecuador.
      Mycorrhizas were collected from 20 individuals along an altitudinal gradient
      between 1850 and 2300 m. Transmission electron microscopy was used to study the
      symbiotic association in detail, and phylogenetic analyses based on nuclear rDNA
      coding for the ribosomal large subunit (nucLSU) were carried out to identify the
      associated mycorrhizal fungi. Microscopic and ultrastructural investigations
      showed the formation of a hyphal sheath, intercellular penetration of fine hyphae
      and colonization of the cortical cells by swollen hyphae of the same fungus.
      These structures were formed by hymenomycetes and ascomycetes. Molecular
      phylogenetic analysis detected seven groups of mycorrhizal fungi belonging to the
      Sebacinales. This is the first study to obtain evidence of ectendomycorrhizas in
      the Vaccinioideae. The ascomycetous nucLSU sequences belonged to members of the
      Leotiomycetes. The ectendomycorrhiza of C. nobilis with Sebacinales is discussed
      as a specific, hitherto undescribed mycorrhizal subcategory of ectomycorrhizas.
      We propose the term 'cavendishioid mycorrhiza'. This subcategory is most likely
      specific for the Andean clade of Ericaceae.

PMID- 16411939
TI  - Oxalate and ferricrocin exudation by the extramatrical mycelium of an
      ectomycorrhizal fungus in symbiosis with Pinus sylvestris.
AB  - Accurate estimates of mycelial exudation in time and space are crucial for the
      assessment of ectomycorrhizal involvement in biogeochemical processes. Knowledge
      of exudation from mycelia of ectomycorrhizal fungi is still limited, especially
      for fungi in symbiosis with a host. Pinus sylvestris seedlings colonized by
      Hebeloma crustuliniforme were grown in aseptic multicompartment dishes. This
      novel system enabled identification of exudates originating only from
      extramatrical mycelium. At harvest, hyphal density and numbers were estimated
      using microscopic imaging. A fractal geometric approach was adopted for
      calculation of exudation rates. The main compounds identified were oxalate and
      ferricrocin. The exudation rate for oxalate was 19 +/- 3 fmol per hyphal tip h(
      1) (mean +/- standard error of the mean) or 488 +/- 95 fmol hyphal mm(-2) h(-1).
      Ferricrocin rates were approx. 10 000 times lower. The fractal dimension (D) of
      the mycelia was 1.4 +/- 0.1, suggesting an explorative growth. Potassium
      nutrition was a significant regulatory factor for ferricrocin but not oxalate.
      The results suggest that hyphal exudation may alter the chemical conditions of
      soil microsites and affect mineral dissolution. Calculations also indicated that
      oxalate exudation may be a significant carbon sink.

PMID- 16411940
TI  - Differential modulation of host plant delta13C and delta18O by native and
      nonnative arbuscular mycorrhizal fungi in a semiarid environment.
AB  - Native, drought-adapted arbuscular mycorrhizal fungi (AMF) often improve host
      plant performance to a greater extent than nonnative AMF in dry environments.
      However, little is known about the physiological basis for this differential
      plant response. Seedlings of Olea europaea and Rhamnus lycioides were inoculated
      with either a mixture of eight native Glomus species or with the nonnative Glomus
      claroideum before field transplanting in a semiarid area. Inoculation with native
      AMF produced the greatest improvement in nutrient and water status as well as in
      long-term growth for both Olea and Rhamnus. Foliar delta18O measurements
      indicated that native AMF enhanced stomatal conductance to a greater extent than
      nonnative AMF in Olea and Rhamnus.delta13C data showed that intrinsic water-use
      efficiency in Olea was differentially stimulated by native AMF compared with
      nonnative AMF. Our results suggest that modulation of leaf gas exchange by
      native, drought-adapted AMF is critical to the long-term performance of host
      plants in semiarid environments. delta18O can provide a time-integrated measure
      of the effect of mycorrhizal infection on host-plant water relations.

PMID- 16411941
TI  - Activities of chitinolytic enzymes during primary and secondary colonization of
      wood by basidiomycetous fungi.
AB  - The nitrogen (N) content of wood is usually suboptimal for fungal colonization.
      During decomposition of wood, an increasing fraction of the N becomes
      incorporated into fungal mycelium. Between 5 and 50% of the N in wood-degrading
      mycelium may be incorporated into chitin. Chitinolytic enzymes render this N
      available for re-utilization. Here, the activities of chitinolytic enzymes
      produced by wood-rotting fungi during degradation of spruce (Picea abies) wood
      were quantified in situ using fluorogenic 4-methylumbelliferyl substrates. A new
      method was developed that enables spatial quantification of enzyme activities on
      solid surfaces. All of the three tested fungi produced endochitinases,
      chitobiosidases and N-acetylhexosaminidases during colonization of wood. N
      acetylhexosaminidase activity, and in some cases also chitobiosidase and
      endochitinase activities, were higher during secondary overgrowth of another
      fungus than during primary colonization of noncolonized wood. The results suggest
      that wood-degrading fungi degrade their own cell walls as well as the hyphae of
      earlier colonizers. Recycling of cell wall material within single mycelia and
      between fungal individuals during succession may lead to retention of N within
      woody debris.

PMID- 16411942
TI  - Routes of pyruvate synthesis in phosphorus-deficient lupin roots and nodules.
AB  - Here, nodulated lupins (Lupinus angustifolius (cv Wonga)) were hydroponically
      grown at low phosphate (LP) or adequate phosphate (HP). Routes of pyruvate
      synthesis were assessed in phosphorus (P)-starved roots and nodules, because P
      starvation can enhance metabolism of phosphoenolpyruvate (PEP) via the
      nonadenylate-requiring PEP carboxylase (PEPc) route. Since nodules and roots may
      not experience the same degree of P stress, it was postulated that decreases in
      metabolic inorganic phosphorus (Pi) of either organ, should favour more pyruvate
      being synthesized from PEPc-derived malate. Compared with HP roots, the LP roots
      had a 50% decline in Pi concentrations and 55% higher ADP : ATP ratios. However,
      LP nodules maintained constant Pi levels and unchanged ADP : ATP ratios, relative
      to HP nodules. The LP roots had greater PEP metabolism via PEPc and synthesized
      more pyruvate from PEPc-derived malate. In nodules, P supply did not influence
      PEPc activities or levels of malate-derived pyruvate. These results indicate that
      nodules were more efficient than roots in maintaining optimal metabolic Pi and
      adenylate levels during LP supply. This caused an increase in PEPc-derived
      pyruvate synthesis in LP roots, but not in LP nodules.

PMID- 16411943
TI  - Adaptive evolution of reproductive and vegetative traits driven by breeding
      systems.
AB  - The evolution of inflorescence size, a key trait in reproductive success, was
      studied in the genus Acer under a perspective of adaptive evolution. Breeding
      systems, hypothesized to indicate different levels of mating competition, were
      considered as the selective scenarios defining different optima of inflorescence
      size. Larger inflorescences, which increase male fitness by generating larger
      floral displays, were hypothesized to be selected under scenarios with higher
      competition with unisexuals. An identical approach was used to test if the same
      selective regimes could be driving the evolution of leaf size, a vegetative trait
      that was found to be correlated with inflorescence size. A Brownian motion model
      of inflorescence/leaf-size evolution (which cannot distinguish between changes
      caused by pure drift processes and changes caused by natural selection in rapidly
      and randomly changing environments) was compared with several adaptive Ornstein
      Uhlenbeck (OU) models, which can quantify the effects of both stochasticity and
      natural selection. The best-fitting model for inflorescence/leaf-size evolution
      was an OU model with three optima that increased with the level of mating
      competition. Both traits evolved under the same selective regimes and in the same
      direction, confirming a pattern of correlated evolution. These results show that
      a selective regime hypothetically related to the evolution of a reproductive
      trait can also explain the evolution of a vegetative trait.

PMID- 16411944
TI  - Pollinator limitation and inbreeding depression in orchid species with and
      without nectar rewards.
AB  - Many orchids produce no nectar rewards. Foraging pollinators should visit more
      flowers per inflorescence in species with nectar, which could increase
      geitonogamous self-fertilization. If a history of selfing decreases genetic load,
      then nectar-producing orchids should harbour lower inbreeding depression than
      nectarless species. Here, I tested this hypothesis by quantifying inbreeding
      depression and pollinator limitation in populations of three closely related
      orchid species, one of which provides nectar. I also compared inbreeding
      depression for nectarless and nectar-producing species of orchids using published
      studies. All field populations expressed pollinator limitation, but the nectar
      providing species was intermediate to the two nectarless species. All populations
      expressed inbreeding depression, and levels increased in later life-history
      stages. There was no tendency for nectarless species to express higher inbreeding
      depression either in experiments or published studies. Nectarless orchids may not
      express higher levels of inbreeding depression because pollinators fail to visit
      more flowers in nectar-bearing species, because such visitations do not result in
      greater selfing, and/or because higher selfing may be ineffective in purging the
      mutations that cause load.

PMID- 16411945
TI  - Reciprocal hybridization at different times between Senecio flavus and Senecio
      glaucus gave rise to two polyploid species in north Africa and south-west Asia.
AB  - The analysis of hybrid plant taxa using molecular methods has considerably
      extended understanding of possible pathways of hybrid evolution. Here, we
      investigated the origin of the tetraploid Senecio mohavensis ssp. breviflorus and
      the hexaploid Senecio hoggariensis by sequencing of nuclear and chloroplast DNA,
      and by analysis of the distribution of taxon-specific amplified fragment length
      polymorphism (AFLP) fragments. Both taxa originated from hybridization between
      the diploid Senecio flavus and Senecio glaucus. Whereas S. glaucus was the female
      parent in the origin of S. mohavensis ssp. breviflorus, S. flavus was the female
      parent in the origin of S. hoggariensis. The distribution of AFLP fragments
      suggests that S. hoggariensis is an allohexaploid species with two diploid
      genomes of S. glaucus and one diploid genome of S. flavus. The high frequency of
      S. flavus-specific fragments in S. mohavensis ssp. breviflorus is explained
      either as the result of introgression between a primary hybrid and S. flavus or
      as the result of intergenomic recombination in a primary hybrid. These two
      alternative processes cannot easily be distinguished.

PMID- 16411946
TI  - Up against the wall: arabinogalactan-protein dynamics at cell surfaces.

PMID- 16411947
TI  - Rubisco synthesis, turnover and degradation: some new thoughts on an old problem.

PMID- 16411948
TI  - Chlorophyll fluorescence and ecophysiology: seeing red?

PMID- 16411949
TI  - Plant metabolomics: from holistic hope, to hype, to hot topic.
AB  - In a short time, plant metabolomics has gone from being just an ambitious concept
      to being a rapidly growing, valuable technology applied in the stride to gain a
      more global picture of the molecular organization of multicellular organisms. The
      combination of improved analytical capabilities with newly designed, dedicated
      statistical, bioinformatics and data mining strategies, is beginning to broaden
      the horizons of our understanding of how plants are organized and how metabolism
      is both controlled but highly flexible. Metabolomics is predicted to play a
      significant, if not indispensable role in bridging the phenotype-genotype gap and
      thus in assisting us in our desire for full genome sequence annotation as part of
      the quest to link gene to function. Plants are a fabulously rich source of
      diverse functional biochemicals and metabolomics is also already proving valuable
      in an applied context. By creating unique opportunities for us to interrogate
      plant systems and characterize their biochemical composition, metabolomics will
      greatly assist in identifying and defining much of the still unexploited
      biodiversity available today.

PMID- 16411950
TI  - Developmental and seasonal expression of PtaHB1, a Populus gene encoding a class
      III HD-Zip protein, is closely associated with secondary growth and inversely
      correlated with the level of microRNA (miR166).
AB  - In contrast to our knowledge of the shoot apical meristem, our understanding of
      cambium meristem differentiation and maintenance is limited. Class III
      homeodomain leucine-zipper (HD-Zip) proteins have been shown to play a regulatory
      role in vascular differentiation. The hybrid aspen (Populus tremulaxPopulus alba)
      class III HD-Zip transcription factor (PtaHB1) and microRNA 166 (Pta-miR166)
      family were cloned from hybrid aspen using a combination of in silico and
      polymerase chain reaction methods. Expression analyses of PtaHB1 and Pta-miR166
      were performed by Northern blot analysis. The expression of PtaHB1 was closely
      associated with wood formation and regulated both developmentally and seasonally,
      with the highest expression during the active growing season. Also, its
      expression was inversely correlated with the level of Pta-miR166. Pta-miR166
      directed cleavage of PtaHB1 in vivo was confirmed using modified 5'-rapid
      amplification of cDNA ends (RACE). The expression of Pta-miR166 was much higher
      in the winter than in the growing seasons, suggesting seasonal and developmental
      regulation of microRNA in this perennial plant species.

PMID- 16411951
TI  - Salt stress upregulates periplasmic arabinogalactan proteins: using salt stress
      to analyse AGP function.
AB  - Arabinogalactan proteins (AGPs) are implicated in cell expansion by unknown
      mechanisms, thus AGP content and cell-expansion rate might be correlated. We used
      Yariv reagent to quantify release rates and distribution of AGP at the cell
      surface of tobacco BY-2 cells: plasma membrane (M); soluble periplasmic AGPs
      released by cell rupture (S); cell wall (W); and growth medium (Gsink). In
      contrast to earlier reports, we observed massive upregulation of AGPs in salt
      stressed cells, and hence the absence of a simple, direct cause-and-effect
      relationship between growth rate and AGP release. There was a more subtle
      connection. A dynamic flux model, M-->S-->W-->Gsink, indicated that turnover was
      nondegradative, with little free diffusion of AGPs trapped in the pectic matrix
      of nonadapted cells where transmural migration of high molecular-weight AGPs
      occurred mainly by plug flow (apposition and extrusion). In contrast, however, an
      up to sixfold increased AGP release rate in the slower-growing salt-adapted cells
      indicated a greatly increased rate of AGP diffusion through a much more highly
      porous pectic network. We hypothesize that classical AGPs act as pectin
      plasticizers. This explains how beta-D-glycosyl Yariv reagents might inhibit
      expansion growth by crosslinking monomeric AGPs, and thus mimic an AGP loss-of
      function mutation.

PMID- 16411952
TI  - A dynamic model of Rubisco turnover in cereal leaves.
AB  - A simple, improved model of Rubisco synthesis and degradation in cereal leaves is
      developed using data obtained over the leaf lifespan to return maximum likelihood
      values for Rubisco proteolysis and biosynthesis. It assumes that the time course
      of leaf Rubisco content can be described using a log-normal curve, and
      degradation of the Rubisco pool occurs exponentially. Curve parameters give an
      insight into how Rubisco dynamics differ among treatments or genotypes; also,
      statistical analyses can be performed more easily, requiring fewer data and
      allowing more flexibility in sampling than previous studies. Predicted patterns
      of synthesis correlate well with independent rbc gene transcript data. Rubisco
      degradation is a first-order decay process, and biosynthesis correlates with leaf
      elongation rates. As Rubisco degradation takes place according to first-order
      kinetics, control of leaf Rubisco concentration must be exerted by adjustment of
      biosynthetic, rather than proteolytic, rates.

PMID- 16411953
TI  - Within and between population variation for zinc and nickel accumulation in two
      species of Thlaspi (Brassicaceae).
AB  - In this study, the differences in zinc (Zn) and nickel (Ni) hyperaccumulation
      were investigated between three populations of Thlaspi pindicum together with
      genetic variation within populations of T. pindicum and Thlaspi alpinum var.
      sylvium, both serpentine endemics. Three experiments were conducted under
      standard conditions in hydroponic assay. Each experiment contained three
      treatments of metal: 100 microm Zn, 100 microm Ni, and combined 100/100 microm
      Zn/Ni. Genetic variation within populations was determined using maternal
      families. No genetic variation within populations was found for either Zn or Ni
      hyperaccumulation for both T. pindicum and T. alpinum var. sylvium, but
      differences were observed for both Zn and Ni hyperaccumulation between
      populations of T. pindicum. In combined Zn/Ni treatments, Zn inhibited Ni
      translocation in both species, which is unexpected considering that these species
      are serpentine endemics and well known Ni hyperaccumulators. The lack of genetic
      variation for metal hyperaccumulation is possibly due to inbreeding. Since Zn
      hyperaccumulation is not manifested in the field, inadvertent uptake of Zn is a
      plausible hypothesis for its preferential uptake.

PMID- 16411954
TI  - Triticum aestivum shows a greater biomass response to a supply of aluminium
      phosphate than Lupinus albus, despite releasing fewer carboxylates into the
      rhizosphere.
AB  - The relationship between carboxylate release and the ability of plants to access
      phosphorus from AlPO4 and to detoxify aluminium was studied by comparing species
      with a low and high rate of carboxylate release, Triticum aestivum (wheat) and
      Lupinus albus (white lupin), respectively. Species were supplied with P at 10,
      20, 40 or 100 mg P kg-1 sand in the form of sparingly soluble AlPO4 or soluble
      KH2PO4; control plants did not receive any P. Triticum aestivum was significantly
      better than L. albus at accessing P from AlPO4, despite accumulating fewer
      carboxylates in its rhizosphere. Rhizosphere pH of L. albus did not vary with
      form or level of P supply, while the rhizosphere pH of T. aestivum increased with
      the level of P supplied. Based on the evidence in the present study, a model is
      proposed to explain the poor performance of L. albus, whereby the release of
      carboxylates and associated protons reduces the chelating ability of exuded
      carboxylates, thus reducing P acquisition and increasing Al toxicity.

PMID- 16411955
TI  - Chlorophyll content and fluorescence responses cannot be used to gauge reliably
      phytoplankton biomass, nutrient status or growth rate.
AB  - To consider the relationship between chlorophyll a (Chl a) content and
      phytoplankton growth and nutrient status, four phytoplankton species were grown
      in nitrogen (N)-limited [and, for one species, phosphorus (P)-limited] culture
      and measurements were made of CNP biomass, in vivo and in vitro Chl a content,
      the ratio of variable to maximum fluorescence (FV/FM) and the performance index
      for photosynthesis, PIABS (a derivative of the O-J-I-P analysis of photosystem II
      functionality). Interspecies differences plus the development of intraspecies
      differences during nutrient stress produced c. 10-fold variations in Chl : C.
      Estimates of C from in vivo Chl content were better than those from extracted Chl
      content, as the decline in Chl : C during nutrient stress was offset in part by
      increased Chl fluorescence. FV/FM was not a robust indicator of nutrient status
      or relative growth rate. Responses of FV/FM in cells re-fed the limiting nutrient
      showed no consistent pattern with which to gauge nutrient status. PIABS showed
      some promise as an indicator of nutrient status and relative growth rate. Chl a
      content and fluorescence parameters do not deserve the unquestioned status they
      usually enjoy as indicators of biomass and physiological status.

PMID- 16411956
TI  - Shoot life span in relation to successional status in deciduous broad-leaved tree
      species in a temperate forest.
AB  - In trees, leaf life span is closely related to successional status. Although
      leaves are attached to shoots, shoot life span has been insufficiently studied in
      the context of ecological systems. Interspecific variation in shoot survivorship
      was investigated over 27 months in 15 temperate hardwood tree species.
      Relationships between shoot architecture and shoot survival were also
      investigated. Shoot life span was shortest in early successional species, and
      longest in late successional species, in each of the families Betulaceae and
      Fagaceae. In Salicaceae, all of which were early successional species, shoot life
      span was longer in mountainous than in riparian species. Early successional or
      riparian species distributed longer shoots densely, even in proximal positions on
      mother shoots, resulting in mutual shading and consequent early and massive shoot
      shedding. By contrast, late successional or mountainous species concentrated
      shoots in distal positions, allowing shoots to receive equally favorable light,
      resulting in a longer life span. These results reveal close relationships between
      shoot life span and environmental resource availability or successional status
      and suggest a causal relationship between shoot shedding and shoot architecture.

PMID- 16411957
TI  - Baobab trees (Adansonia) in Madagascar use stored water to flush new leaves but
      not to support stomatal opening before the rainy season.
AB  - Baobab trees (Adansonia, Bombacaceae) are widely thought to store water in their
      stems for use when water availability is low. We tested this hypothesis by
      assessing the role of stored water during the dry season in three baobab species
      in Madagascar. In the dry season, leaves are present only during and after leaf
      flush. We quantified the relative contributions of stem and soil water during
      this period through measures of stem water content, sap flow and stomatal
      conductance. Rates of sap flow at the base of the trunk were near zero,
      indicating that leaf flushing was almost entirely dependent on stem water. Stem
      water content declined by up to 12% during this period, yet stomatal conductance
      and branch sap flow rates remained very low. Stem water reserves were used to
      support new leaf growth and cuticular transpiration, but not to support stomatal
      opening before the rainy season. Stomatal opening coincided with the onset of sap
      flow at the base of the trunk and occurred only after significant rainfall.

PMID- 16411958
TI  - Competition- and resource-mediated tradeoffs between growth and defensive
      chemistry in trembling aspen (Populus tremuloides).
AB  - Costs of defense are thought to maintain genetic variations in the expression of
      defense within plant populations. As with many plant species, aspen exhibits
      considerable variation in allocation to secondary metabolites. This study
      examined the independent and interactive effects of genotype, soil fertility and
      belowground competition on defensive chemistry and growth in trembling aspen
      (Populus tremuloides). Four aspen genotypes were grown with high and low soil
      fertility, and with and without root competition. Physiological, morphological
      and allocational determinants of growth were measured to identify growth-defense
      tradeoffs. Nutrient limitation and competition decreased growth, leaf mass ratio,
      leaf nitrogen concentration and photosynthesis, and increased root : shoot ratio
      and leaf condensed tannin concentrations. The competition treatment also resulted
      in increased leaf phenolic glycoside (PG) concentrations. Aspen growth was
      negatively correlated with PG concentrations under low fertility with
      competition. The relationship between growth and its major determinants was also
      negatively related to foliar condensed tannins expressed as a proportion of tree
      mass, indicating an additional indirect cost of allocation to secondary
      metabolites.

PMID- 16411959
TI  - Phytotoxicity dynamics of decaying plant materials.
AB  - Allelopathic effects of plant litter have been extensively studied, but less
      attention has been given to the dynamics of phytotoxicity during the
      decomposition processes. Decomposition experiments were carried out on above- and
      below-ground plant materials of 25 species of different functional groups
      (nitrogen fixer, forbs, woody and grasses-sedges) in aerobic and anaerobic
      conditions. The phytotoxicity of aqueous extracts of decomposing material was
      assessed by bioassay in 30 d of laboratory and 90 d of litterbag decomposition
      experiments. Phytotoxicity was widespread with c. 90% of the tested species
      showing significant phytotoxic releases. Phytotoxicity largely varied between
      different plant functional groups (nitrogen fixer>forbs=woody>>grasses-sedges)
      and was higher for leaf compared with root materials. In all species tested
      during decomposition, phytotoxicity rapidly decreased in aerobic conditions but
      sharply increased and became stable in anaerobic conditions. The results
      demonstrate an unexpectedly widespread occurrence of phytotoxicity with clear
      dynamic patterns during the decomposition processes of plant materials. The
      ecological consequences of this might have been underestimated.

PMID- 16411960
TI  - Do ectomycorrhizas alter leaf-litter decomposition in monodominant tropical
      forests of Guyana?
AB  - This work tested the hypothesis that ectomycorrhizas (EM) of Dicymbe corymbosa
      alter leaf-litter decomposition and residual litter quality in tropical forests
      of Guyana. Mass loss of leaf litter in litter bags was determined on three
      occasions, in two experiments, during a 12-month period. Paired root-exclusion
      plots were located randomly within a D. corymbosa forest. Both D. corymbosa and
      mixed-species leaf litters were reciprocally transplanted into their respective
      forest types. Elemental analysis was performed on the residual D. corymbosa leaf
      litter after 1 yr. Leaf litter mass loss in the D. corymbosa forest was not
      influenced by EM, despite high EM colonization. Elemental analysis of D.
      corymbosa leaf litter residues demonstrated reduced calcium levels in the
      presence of EM, which were negatively correlated with EM rootlet-colonizing mass.
      The lack of EM effect on the litter decomposition rate, coupled with high EM
      colonization, suggests an important but indirect role in mineral nutrient
      acquisition. Lowered Ca concentration in leaf litter exposed to EM may suggest a
      high Ca demand by the ectotroph system.

PMID- 16411961
TI  - Genetic variation of ecophysiological traits in two gynodioecious species of
      Schiedea (Caryophyllaceae).
AB  - Evolution of dimorphic breeding systems may involve changes in ecophysiological
      traits as well as floral morphology because of greater resource demands on
      females. Differences between related species suggest that ecophysiological traits
      should be heritable, and species with higher female frequencies should show
      greater sexual differentiation. We used modified partial diallel crossing designs
      to estimate narrow-sense heritabilities and genetic correlations of sex-specific
      ecophysiological and morphological traits in closely related gynodioecious
      Schiedea salicaria (13% females) and Schiedea adamantis (39% females). In S.
      salicaria, hermaphrodites and females differed in photosynthetic rate and
      specific leaf area (SLA). Narrow-sense heritabilities were significant for
      stomatal conductance, SLA and inflorescence number in hermaphrodites, and for SLA
      and inflorescence number in females. Schiedea adamantis had no sexual dimorphism
      in measured traits; stomatal conductance, stem number and inflorescence number
      were heritable in females, and stem number was heritable in hermaphrodites. In
      both species, significant genetic correlations of traits between sexes were rare,
      indicating that traits can evolve independently in response to sex-differential
      selection. Significant genetic correlations were detected between certain traits
      within sexes of both species. Low heritability of some ecophysiological traits
      may reflect low additive genetic variability or high phenotypic plasticity in
      these traits.

PMID- 16411962
TI  - Multiple intercontinental dispersals shaped the distribution area of Hordeum
      (Poaceae).
AB  - The grass genus Hordeum (Poaceae, Triticeae), comprising 31 species distributed
      in temperate and dry regions of the world, was analysed to determine the relative
      contributions of vicariance and long-distance dispersal to the extant
      distribution pattern of the genus. Sequences from three nuclear regions (DMC1, EF
      G and ITS) were combined and analysed phylogenetically for all diploid (20
      species) and two tetraploid Hordeum species and the outgroup Psathyrostachys.
      Ages of clades within Hordeum were estimated using a penalized likelihood
      analysis of sequence divergence. The sequence data resulted in an almost fully
      resolved phylogenetic tree that allowed the reconstruction of intrageneric
      migration routes. Hordeum evolved c. 12 million years ago in South-west Asia and
      spread into Europe and Central Asia. The colonization of the New World and South
      Africa involved at least six intercontinental exchanges during the last 4 million
      years (twice Eurasia-North America, North America-South America, twice South
      America-North America and Europe-South Africa). Repeated long-distance dispersal
      between the northern and southern hemisphere were important colonization
      mechanisms in Hordeum.

PMID- 16411963
TI  - Spatio-temporal variation in pollen limitation and reproductive success of two
      scape morphs in Primula farinosa.
AB  - In plant populations where reproductive output is limited by pollinator
      visitation, plants with attractive floral displays should have a selective
      advantage. We examined the effect of inflorescence height on pollination success
      in Primula farinosa, which is dimorphic for scape length. To test the hypothesis
      that fruit and seed initiation are more strongly pollen-limited in the short
      scaped than in the long-scaped morph, and that this difference is affected by
      spatio-temporal variation in pollen limitation, we conducted a hand-pollination
      experiment in four populations over 2 yr. Pollen limitation of fruit initiation
      varied among populations and years, and was stronger in the short-scaped than in
      the long-scaped morph. The results suggest that interactions with pollinators
      will need to be considered for a full understanding of the maintenance of this
      striking polymorphism. The study also shows that, although pollen limitation is
      likely to vary in space and time in many plant species, such variation is not
      necessarily associated with variation in selection on floral characters.

PMID- 16411964
TI  - PHENOPSIS, an automated platform for reproducible phenotyping of plant responses
      to soil water deficit in Arabidopsis thaliana permitted the identification of an
      accession with low sensitivity to soil water deficit.
AB  - The high-throughput phenotypic analysis of Arabidopsis thaliana collections
      requires methodological progress and automation. Methods to impose stable and
      reproducible soil water deficits are presented and were used to analyse plant
      responses to water stress. Several potential complications and methodological
      difficulties were identified, including the spatial and temporal variability of
      micrometeorological conditions within a growth chamber, the difference in soil
      water depletion rates between accessions and the differences in developmental
      stage of accessions the same time after sowing. Solutions were found. Nine
      accessions were grown in four experiments in a rigorously controlled growth
      chamber equipped with an automated system to control soil water content and take
      pictures of individual plants. One accession, An1, was unaffected by water
      deficit in terms of leaf number, leaf area, root growth and transpiration rate
      per unit leaf area. Methods developed here will help identify quantitative trait
      loci and genes involved in plant tolerance to water deficit.

PMID- 16411965
TI  - Surgical outcome and predictive factors in adult patients with intractable
      epilepsy and focal cortical dysplasia.
AB  - OBJECTIVES: To determine the surgical outcome and prognostic factors in adult
      patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS
      AND METHODS: We retrospectively studied the operative outcome in 21 consecutive
      adult patients with FCD who underwent surgical treatment for intractable partial
      epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years).
      The median post-operative follow-up was 2.5 years. The FCD was extratemporal in
      11 patients, involved the temporal lobe in 10 patients, and was multilobar in
      eight patients. Eleven patients (52%) were rendered seizure-free, four patients
      (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94%
      reduction in seizures. A seizure-free outcome was associated with shorter
      duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be
      candidates for surgical treatment of intractable partial epilepsy. Most
      individuals have neocortical, extrahippocampal seizures and approximately 50% of
      patients are rendered seizure-free.

PMID- 16411966
TI  - Focal cortical dysplasia: prevalence, clinical presentation and epilepsy in
      children and adults.
AB  - Focal cortical dysplasias (FCD) are defined as circumscribed malformations of
      cortical development. They result from an impairment of neuronal proliferation,
      migration and differentiation. In the diagnosis of focal epilepsy FCD prevalence
      ranges between 5% and 25%, depending on patient collective and imaging
      techniques. Several 'cryptogenic' epilepsies may be caused by FCD but have not
      been diagnosed because of the lack of high-quality magnetic resonance imaging
      assessment. Retrospective analysis of patients who have undergone epilepsy
      surgery can be biased because of the fact that they represent a mere subset of
      potential FCD diagnoses. Epilepsy typically manifests within the first years of
      life, but has been documented up to the age of 60 years. Cognitive impairment
      commonly accompanies early onset. Epilepsy is often refractory to antiepileptic
      drug (AED) treatment. Clinical observations and pathophysiological findings
      illustrate intrinsic epileptogenicity. Upregulation of drug transporter proteins
      has been found in FCD tissue. There is no specific drug treatment in FCD, as any
      AED used in focal epilepsy could prove effective. A sequential AED therapy should
      be designed individually and take side effects as well as developmental
      progresses into consideration. Fifty to sixty-five percent of FCD patients are
      rendered seizure-free after surgery. Presurgical evaluation should be initiated
      after two unsuccessful AED trials. Both risks and potential benefits regarding
      seizure control and developmental impairment need to be considered on an
      individual basis when deciding between surgical intervention and conservative
      treatment. Current knowledge on epilepsy course and psychomotor development in
      FCD is limited in the absence of qualified long-term studies combining imaging
      with cognitive evaluation.

PMID- 16411967
TI  - Use of levetiracetam in treating epilepsy associated with other medical
      conditions.
AB  - OBJECTIVE: This prospective, open-label study was conducted to evaluate the
      effectiveness, tolerability, and safety of levetiracetam in patients with
      epilepsy in whom unfavorable metabolism, complex drug interactions, or direct
      toxic effects of antiepileptic drugs (AEDs) had caused a worsening of comorbid
      conditions. METHODS: Study design included the introduction of levetiracetam,
      discontinuation of other AEDs, and a serial assessment comprising
      electroencephalograms and blood tests at baseline and 2, 6, and 12 months. Of 21
      patients, 16 had partial and five generalized epilepsy. Concomitant pathologies
      were gastroenterological (six), vascular (four), endocrinological (four), or
      complex conditions including hematological (four) or dermatological (three)
      disease. A change of regimen was necessitated by drug-drug interactions in four
      patients, direct real or potential toxic effects of previous AEDs in 13, and a
      combination of interactions/toxic effects in four. RESULTS: After 12 months, 12
      patients were seizure-free, nine had reductions in seizure frequency of 50-75%,
      and improvement in concomitant medical conditions was observed. No side effects
      were reported. CONCLUSION: Levetiracetam appears to be effective, well tolerated,
      and safe in patients with epilepsy and other medical conditions that are
      difficult to manage because of drug interactions or AED-related side effects.

PMID- 16411968
TI  - White matter hyperintensities and cortical acetylcholinesterase activity in
      parkinsonian dementia.
AB  - OBJECTIVE: To investigate the relationship between the severity of white matter
      hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in
      parkinsonian dementia (PDem). METHODS: PDem (n = 11) and control subjects (n =
      14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron
      emission tomography and magnetic resonance (MR) imaging. Presence of WMH on
      proton density and T2 MR images was scored using a modified version of the semi
      quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]. RESULTS:
      Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis
      rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem
      subjects had higher mean severity of WMH (+20.1%) when compared with control
      subjects (P < 0.05). When WMH severity was entered into the analysis of variance
      model, there was no significant co-variate effect on cortical AChE activity (F =
      0.24, ns). CONCLUSIONS: The concomitant presence of mild to moderate WMH in
      patients with PDem does not have a significant effect on cortical AChE activity.

PMID- 16411969
TI  - Effects of repetitive transcranial magnetic stimulation on voice and speech in
      Parkinson's disease.
AB  - OBJECTIVE: To investigate the effects of repetitive transcranial magnetic
      stimulation (rTMS) on vocal function in Parkinson's disease (PD). MATERIAL AND
      METHODS: Two different sets of rTMS parameters were investigated on 30 patients
      with PD: active or sham 15 Hz rTMS of the left dorsolateral prefrontal cortex
      (LDLPFC) (110% of motor threshold (MT), 3000 pulses per session) and active 5 Hz
      rTMS of the primary motor cortex (M1)-mouth area (90% MT, 2250 pulses per
      session). A blind rater evaluated speech characteristics (acoustic and perceptual
      analysis of voice) and voice-related quality of life (V-RQOL). RESULTS: rTMS of
      LDLPFC resulted in mood amelioration and subjective improvement of the V-RQOL
      only (71.9% improvement, P < 0.001), but not in objective measures such as
      fundamental frequency (P = 0.86) and voice intensity (P = 0.99). On the other
      hand, rTMS of M1-mouth induced a significant improvement of the fundamental
      frequency (12.9% for men and 7.6% for women, P < 0.0001) and voice intensity
      (20.6%, P < 0.0001). CONCLUSIONS: Our findings provide initial evidence that rTMS
      of the primary motor cortex might yield a beneficial effect on vocal function in
      PD.

PMID- 16411970
TI  - Assessing the outcome of stroke: a comparison between MRI and clinical stroke
      scales.
AB  - OBJECTIVES: To assess the correlation of diffusion-weighted (DWI) and perfusion
      weighted imaging (PWI) findings with the severity of acute neurologic deficit and
      their ability to predict short and long-term clinical outcomes of stroke. The
      ability of DWI and PWI to predict the outcome was compared with the ability of
      clinical stroke scales to predict the outcome. METHODS: Forty-eight patients with
      acute stroke underwent diffusion DWI and PWI on the first and eighth day after
      the ictus. Clinical and functional scales were carried out before each scan and 3
      months after the stroke. RESULTS: The volumes of both the DWI and the PWI lesions
      correlated well with the acute neurologic deficit and the final outcome. The
      first day PWI (r = 0.64) and the National Institutes of Health Stroke Scale
      (NIHSS) scores (r = 0.70) correlated well with the final outcome. However, in
      logistic regression analysis, only the NIHSS score at the acute stage was the
      only independent predictor of the long-term clinical outcome. CONCLUSION: While
      the PWI and DWI lesion volumes correlated well with the outcome of the stroke,
      the imaging measurements did not improve the prognostic power over plain clinical
      stroke scale scores.

PMID- 16411971
TI  - Impact of comorbidity on ischemic stroke outcome.
AB  - OBJECTIVE: To evaluate the impact of comorbidity on stroke outcome of patients
      admitted to a general ward (GW) and a stroke unit (SU). METHODS: Data of 266
      patients with acute ischemic stroke (GW: 103, SU: 163) were collected
      prospectively for 13 months. Clinical and radiological findings, and the Charlson
      Comorbidity Index (CCI) were recorded. Predictors of outcome 4 months after
      stroke were analyzed. Favorable outcome was defined as modified Rankin Scale
      (mRS) score of < or = 2, unfavorable as mRS >2. RESULTS: The mean age of the
      patients was 67.2 years (SD = 14.4), the mean CCI 1.2 (SD = 1.4). In univariate
      analysis, small artery disease predicted favorable outcome (P < 0.001) and age (P
      = 0.022), high National Institutes of Health Stroke Scale (NIHSS) score (P <
      0.001), high CCI (P < 0.001), treatment in a GW (P = 0.004), coronary artery
      disease (P = 0.02), dementia (P = 0.009), diabetes (P = 0.005) and atrial
      fibrillation (P < 0.001) unfavorable outcome after 4 months. In multivariate
      analysis, high NIHSS score (P < 0.001), atrial fibrillation (P = 0.004), coronary
      artery disease (P = 0.012) and diabetes (P = 0.031) were predictors of
      unfavorable outcome. CONCLUSIONS: Comorbidity has a significant impact on stroke
      outcome. In addition to stroke severity, atrial fibrillation, coronary artery
      disease and diabetes were predictors of outcome after stroke, but not the sum of
      the CCI.

PMID- 16411972
TI  - Identifying the determinants of 1-year post-stroke outcomes in elderly patients.
AB  - OBJECTIVES: To examine 12-month outcomes and develop predictive models for
      outcomes in elderly stroke patients. METHODS: Prospective study of 186
      consecutive acute stroke patients aged > or = 65 years admitted to a local
      hospital between March 2002 and March 2003. Outcome measurements included
      mortality, functional independence measure (FIM) score and nursing home
      placement. Two predictive models, using multiple logistic regression analysis,
      were developed to identify the factors associated with (i) mortality, and (ii)
      being alive and independent (defined as mean FIM score > or = 90) at 12 months.
      RESULTS: One hundred and seventy two (92%) patients were followed up at 12 months
      post-stroke. Mortality rate was 31%, and was significantly higher in nursing home
      vs non-nursing home origin patients (68% [15/22] vs 25% [38/150]). Nursing home
      placement for non-nursing home origin survivors was 28% (31/112). Age > or = 85
      years was associated with higher mortality (odds ratio = 5.3, 95% confidence
      interval = 1.8-15, P < 0.01) and lower FIM for patients living at home pre
      stroke. Predictive models showed that age, not living at home pre-stroke, pre
      stroke FIM < 108, inability to walk on admission, dysphasia, visual field loss
      and haemorrhagic stroke were associated with worse outcome. CONCLUSIONS:
      Predictive models--by developing new strategies to improve outcomes through
      identifying treatable predictive factors--may be clinically useful in elderly
      stroke patients.

PMID- 16411973
TI  - Incidence and etiology of ischemic stroke in Persian young adults.
AB  - BACKGROUND: Stroke in young adults causes morbidity in this socioeconomically
      active age group. The etiologic frequency of ischemic stroke in young adults
      differs around the world. METHODS: The study population consisted of 314,000
      'young adult' residents in Southern Khorasan province in Iran. All patients with
      stroke are routinely admitted to the Valie Asr tertiary care hospital. Data on
      patients demographics, clinical presentation and investigations of consecutive
      patients aged 15-45 years with ischemic stroke are registered in Southern
      Khorasan stroke data bank for the period March 2000 to March 2005. All patients
      underwent a standard battery of diagnostic investigations by a stroke
      neurologist. The etiologic classification of stroke in the patients was made
      based on the trial of ORG 10172 in acute stroke treatment (TOAST) criteria.
      RESULTS: One hundred and twenty-four patients (60 female, 64 male) were
      prospectively investigated during a 5-year period. The incidence of ischemic
      stroke in young adults was eight cases per 100,000 people per year. Cardioembolic
      mechanism comprised 54% of stroke etiology in young adults. Rheumatic valvular
      disease was present in 32% of the patients and caused 2.5 preventable stroke
      cases per 100,000 'young adults' per year. CONCLUSION: Rheumatic valvular disease
      is the most common cause and a preventable etiology of stroke in Persian young
      adults.

PMID- 16411974
TI  - Relevance of callosal and periventricular MRI lesions to oligoclonal bands in
      multiple sclerosis.
AB  - OBJECTIVES: To evaluate the association between callosal or periventricular
      lesions, and the presence of oligoclonal IgG bands (OB) or the IgG index in
      Japanese patients with multiple sclerosis (MS). MATERIALS AND METHODS: Brain
      magnetic resonance imaging (MRI) was studied in 34 Japanese clinically definite
      MS cases. Sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) imaging
      was added to the routine MRI studies. RESULTS: Among the 34 patients, 20 (59%)
      were OB positive. Among the 20 patients with OB-positive MS, 17 (85%) had
      callosal lesions, although only two (14%) of 14 OB-negative MS patients had
      callosal lesions. The periventricular lesion area was significantly larger in the
      OB-positive patients compared with the OB-negative patients. CONCLUSIONS: The
      present study clearly demonstrated a strong association between the
      periventricular lesions and OB in Japanese MS. Certain OB-related immune
      mechanisms may contribute to the development of callosal and periventricular
      lesions in MS. OB may be an important factor to understand the pathomechanisms of
      MS lesions.

PMID- 16411975
TI  - Respondent burden and patient-perceived validity of the PDQ-39.
AB  - OBJECTIVES: To evaluate the respondent burden and patient-perceived content
      validity of the Parkinson's disease (PD)-specific health status questionnaire PDQ
      39, and the linguistic validity of its revised Swedish version. MATERIALS AND
      METHODS: Eighteen PD patients completed the revised Swedish version of the PDQ
      39. Respondent burden was assessed by recording the time taken to complete the
      questionnaire. Content and linguistic validity was evaluated qualitatively.
      RESULTS: Patients with mild, moderate and advanced PD needed a mean time of 9.5,
      11.3 and 20.1 min, respectively, to complete the PDQ-39. One-third of the
      patients identified irrelevant items and 50% identified important health-related
      areas that were missing. Revisions had eliminated previous linguistic problems
      with the Swedish PDQ-39. CONCLUSIONS: Undue respondent burden challenged the
      appropriateness of the PDQ-39 among patients with more advanced disease. Overall
      content validity was acceptable but compromised by lack of important content
      areas. Observations supported the linguistic validity of the revised Swedish PDQ
      39.

PMID- 16411976
TI  - Affective instability as rapid cycling: theoretical and clinical implications for
      borderline personality and bipolar spectrum disorders.
AB  - OBJECTIVES: The Diagnostic and Statistical Manual of Mental Disorders guidelines
      provide only a partial solution to the nosology and treatment of bipolar disorder
      in that disorders with common symptoms and biological correlates may be
      categorized separately because of superficial differences related to behavior,
      life history, and temperament. The relationship is explored between extremely
      rapid switching forms of bipolar disorder, in which manic and depressive symptoms
      are either mixed or switch rapidly, and forms of borderline personality disorder
      in which affective lability is a prominent symptom. METHODS: A MedLine search was
      conducted of articles that focused on rapid cycling in bipolar disorder,
      emphasizing recent publications (2001-2004). RESULTS: Studies examined here
      suggest a number of points of phenomenological and biological overlap between the
      affective lability criterion of borderline personality disorder and the extremely
      rapid cycling bipolar disorders. We propose a model for the development of
      'borderline' behaviors on the basis of unstable mood states that sheds light on
      how the psychological and somatic interventions may be aimed at 'breaking the
      cycle' of borderline personality disorder development. A review of pharmacologic
      studies suggests that anticonvulsants may have similar stabilizing effects in
      both borderline personality disorder and rapid cycling bipolar disorder.
      CONCLUSIONS: The same mechanism may drive both the rapid mood switching in some
      forms of bipolar disorder and the affective instability of borderline personality
      disorder and may even be rooted in the same genetic etiology. While continued
      clinical investigation of the use of anticonvulsants in borderline personality
      disorder is needed, anticonvulsants may be useful in the treatment of this
      condition, combined with appropriate psychotherapy.

PMID- 16411977
TI  - Topiramate monotherapy in the management of acute mania: results of four double
      blind placebo-controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of topiramate monotherapy in
      adults with acute manic or mixed episodes of bipolar I disorder. METHODS: In four
      trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder,
      history of > or =1 previous manic or mixed episodes, and > or =20 Young Mania
      Rating Scale (YMRS) score were randomized to double-blind treatment with
      topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials
      included an active comparator (lithium, 1500 mg/day). The core study duration in
      all trials was 3 weeks; three trials also had 9-week double-blind extensions. The
      primary efficacy variable was mean change from baseline in YMRS in the core 3
      week study. RESULTS: Changes in YMRS score during 3 weeks were not significantly
      different for topiramate versus placebo (mean YMRS reductions, -5.1 to -8.4).
      Mean YMRS reductions in lithium-treated groups were significantly greater (p < or
      = 0.001 versus placebo and topiramate). A similar pattern was observed after 12
      weeks of double-blind treatment in studies with double-blind extensions.
      Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently
      associated with topiramate than with placebo. CONCLUSIONS: These studies do not
      support the efficacy of topiramate as monotherapy in acute mania or mixed
      episodes in adults with bipolar I disorder. Topiramate was not associated with
      mood destabilization measured as mania exacerbation or treatment-emergent
      depression. Lithium was confirmed as an effective therapy in this population.

PMID- 16411978
TI  - Stroop performance in bipolar disorder: further evidence for abnormalities in the
      ventral prefrontal cortex.
AB  - OBJECTIVES: Bipolar patients are impaired in Stroop task performance, a measure
      of selective attention. Structural and functional abnormalities in task
      associated regions, in particular the prefrontal cortex (PFC), have been reported
      in this population. We aimed to examine the relationship between functional
      abnormalities, impaired task performance and the severity of depressive symptoms
      in bipolar patients. METHODS: Remitted bipolar patients (n = 10; all medicated),
      either euthymic or with subsyndromal depression, and age-matched control subjects
      (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli,
      naming the colour of the ink. Neural response was measured using functional
      magnetic resonance imaging. We computed between-group differences in neural
      response and within-group correlations with mood and anxiety. RESULTS: There were
      no significant between-group differences in task performance. During the Stroop
      condition, controls demonstrated greater activation of visual and dorsolateral
      and ventrolateral prefrontal cortical areas; bipolar patients demonstrated
      relative deactivation within orbital and medial prefrontal cortices. Depression
      scores showed a trend towards a negative correlation with the magnitude of
      orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety
      correlated positively with activation of dorsolateral PFC and precuneus in
      controls. CONCLUSIONS: Our findings confirm previous reports of decreased ventral
      prefrontal activity during Stroop task performance in bipolar patients, and
      suggest a possible negative correlation between this and depression severity in
      bipolar patients. These findings further highlight the ventromedial PFC as a
      potential candidate for illness related dysfunction in bipolar disorder.

PMID- 16411979
TI  - Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder
      and recurrent major depressive disorder.
AB  - OBJECTIVE: Patients with remitted major depressive disorder (MDD) and bipolar
      disorder have persistent impairments in executive function and verbal memory that
      may represent endophenotypic abnormalities. In this study, we examine
      neurocognitive function in a sample of euthymic young adults with bipolar
      spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to
      well-matched samples of young adults with recurrent MDD and controls. METHOD:
      Twenty-one euthymic young adult patients with BSD were compared with 42 young
      adult patients with MDD and 33 controls on a neuropsychological battery assessing
      attention, executive function and verbal memory. RESULTS: Patients with BSD were
      significantly more impaired than MDD patients and controls on tests of executive
      function and verbal memory. MDD patients did not differ significantly from
      controls on verbal memory function but performed less well on a test of executive
      function. CONCLUSION: Euthymic young adults with BSD had greater impairment on
      neurocognitive measures associated with prefrontal and hippocampal function than
      MDD patients and controls. This is a reflection of a strong bipolar diathesis in
      the BSD group rather than being a consequence of a more severe unipolar illness.

PMID- 16411980
TI  - Fronto-temporal function may distinguish bipolar disorder from schizophrenia.
AB  - OBJECTIVES: There is evidence for differential neural alterations within the
      prefrontal cortex (PFC) in bipolar disorder I (BDI) and schizophrenia that may
      translate into different cognitive deficits. Our objective was to compare the
      cognitive profile of stable BDI and schizophrenic patients using
      neuropsychological tasks which utilize frontal systems but differ in terms of the
      exact neural circuits and cognitive processes involved. METHODS: We studied 43
      patients with BDI, 54 with schizophrenia and 46 matched healthy participants. All
      participants completed (i) the Wisconsin Card Sorting Test (WCST) which is known
      to recruit the dorsal and ventral PFC, (ii) the verbal fluency task (VFT), which
      engages frontal-temporal regions, and (iii) the Stroop Colour Word Test (SWCT)
      which depends on the integrity of the cingulo-frontal network. A series of
      multivariate analyses examined differences between the cognitive profiles of BD
      and schizophrenic patients relative to that of healthy participants controlling
      for general intellectual ability and gender. RESULTS: Bipolar disorder I patients
      showed minimal verbal fluency impairment while schizophrenic patients
      demonstrated marked deficits on this task relative to the control and BDI groups.
      The two patient groups had comparable performance on the WCST. In the SWCT,
      schizophrenic patients showed impairment in both congruent and incongruent
      conditions while BD patients had deficits only in the latter. CONCLUSIONS:
      Absence of significant verbal fluency abnormalities and by inference dysfunction
      in the associated fronto-temporal circuitry may distinguish BDI from
      schizophrenia. Both disorders may show impairment in tasks involving cingulo
      frontal networks with evidence of greater cingulate dysfunction in schizophrenia.

PMID- 16411981
TI  - Diagnostic subtypes of bipolar disorder in older versus younger adults.
AB  - OBJECTIVE: To investigate differences in diagnostic subtypes of bipolar disorder
      as according to ICD-10 between patients whose first contact with psychiatric
      health care occurs late in life (over 50 years of age) and patients who have
      first contact earlier in life (50 years of age or below). METHODS: From 1994 to
      2002 all patients who received a diagnosis of a manic episode or bipolar disorder
      at initial contact with the mental healthcare system, whether outpatient or
      inpatient, were identified in Denmark's nationwide register. RESULTS: A total of
      852 (49.6%) patients, who were over age 50, and 867 patients, who were 50 or
      below, received a diagnosis of a manic episode or bipolar disorder at the first
      contact ever. Older inpatients presented with psychotic symptoms (35.4%)
      significantly less than younger inpatients (42.6%) due specifically to a lower
      prevalence of manic episodes with psychotic symptoms. Conversely, older
      inpatients more often presented with severe depressive episodes with psychotic
      symptoms than younger inpatients (32.0% versus 17.0%). Among outpatients, no
      significant differences were found between patients older than 50 years and
      patients 50 years of age or younger. However, a bimodal distribution of age at
      first outpatient contact was found with an intermode of 65 years and outpatients
      older than 65 years more often presented with severe depressive episodes with
      psychosis. CONCLUSIONS: Bipolar patients who are older at first psychiatric
      hospitalization (>50 years) present less with psychotic manic episodes and more
      with severe depressive episodes with psychosis than younger patients. The
      distribution of age at first outpatient contact is bimodal with an intermode of
      65 years and outpatients older than 65 years more often present with severe
      depressive episodes with psychosis.

PMID- 16411982
TI  - Regional cerebral cortical thinning in bipolar disorder.
AB  - OBJECTIVE: This study was conducted to explore differences in cortical thickness
      between subjects with bipolar disorder and healthy comparison subjects using
      cortical surface-based analysis. METHODS: Brain magnetic resonance images were
      acquired from 25 subjects with bipolar disorder and 21 healthy comparison
      subjects. Cortical surface-based analysis was conducted using the Freesurfer
      application. Group differences in cortical thickness, defined by the distance
      from gray/white boundary to the pial surface, were assessed using statistical
      difference maps. RESULTS: Subjects with bipolar disorder exhibited significantly
      decreased cortical thickness in left cingulate cortex, left middle frontal
      cortex, left middle occipital cortex, right medial frontal cortex, right angular
      cortex, right fusiform cortex and bilateral postcentral cortices, relative to
      healthy comparison subjects (all p < 0.001). Duration of illness in bipolar
      subjects was inversely correlated with the cortical thickness of the left middle
      frontal cortex. CONCLUSIONS: Cortical thinning was present in multiple prefrontal
      cortices in bipolar disorder. There was also cortical thinning in sensory and
      sensory association cortices, which has not been reported in previous studies
      using region-of-interest or voxel-based morphometry methods. Cortical thinning
      observed in the current study may be related to impairment of emotional,
      cognitive, and sensory processing in bipolar disorder but longitudinal studies
      will be necessary to test this hypothesis.

PMID- 16411983
TI  - A double-blind, placebo-controlled trial of adjunctive donepezil in treatment
      resistant mania.
AB  - INTRODUCTION: Because there is a high rate of partial response to standard
      thymoleptic medication, novel augmentation strategies for treatment-resistant
      bipolar disorder are needed. In an open trial, donepezil augmentation was
      associated with improvement in manic symptoms in 9 of 11 subjects. METHOD: We
      conducted a 6-week, double-blind, placebo-controlled trial of donepezil for
      treatment-resistant bipolar mania. Eligible subjects had a Young Mania Rating
      Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic
      levels of lithium or valproate. Subjects who completed the trial were eligible
      for an 8-week open trial of donepezil. Subjects were started on donepezil 5
      mg/day and were eligible for dose increase to 10 mg/day after 4 weeks. RESULTS:
      Twelve subjects were enrolled. Eleven subjects received at least 1 week of study
      medication and were included in the analysis. No subjects in the donepezil group
      (0/6) and 60% (3/5) in the placebo group met response criteria of >30% reduction
      in YMRS score (Fisher's Exact p = 0.061). YMRS scores were higher at trial
      endpoint in the donepezil group 20.17 (3.66) compared with the placebo group
      [11.20 (4.60), Z = -2.476, p = 0.01]. There were no differences at trial endpoint
      in Hamilton Rating Scale for Depression (HAM-D) or Brief Psychiatric Rating Scale
      (BPRS) scores in either the intent-to-treat or the completer analyses.
      CONCLUSIONS: Donepezil does not appear to be an effective adjunctive treatment
      for refractory manic symptoms. The strength of the conclusion of this trial is
      limited by the possibility of a false-negative result due to the small sample.

PMID- 16411984
TI  - Stability of estimated IQ across mood state in patients with bipolar disorder.
AB  - OBJECTIVES: The goal of this study was to assess the impact of mania symptoms on
      the stability of the American version of the National Adult Reading Test (ANART),
      a measure that provides a putative estimate of premorbid intellectual
      functioning. METHODS: The ANART was administered to a sample of 10 inpatients
      with bipolar disorder who were experiencing an acute episode of mania. During a
      subsequent follow-up visit during which these individuals exhibited at most
      minimal mood symptoms, the ANART was re-administered. RESULTS: ANART estimated
      intelligence quotient (IQ) scores during mania and affective stability were
      assessed in the 10 patients using a paired sample t-test. Within-subject
      performance across the two mood states did not significantly differ [t(9) = 
      1.24, p = 0.25]. Additionally, the greatest individual difference across mood
      states was only 3.68 points, and the average estimated IQ difference across mood
      states was 1.66. CONCLUSIONS: While the results are preliminary and based on a
      small sample, the highly consistent scores achieved across mood states in this
      study suggest that the ANART is a reliable indicator of premorbid IQ.

PMID- 16411985
TI  - Neuropsychological impairment in bipolar disorder: the relationship with
      glucocorticoid receptor function.
AB  - OBJECTIVE: Basal levels of glucocorticoids, such as cortisol, are generally
      unaltered in bipolar disorder. However, neuroendocrine tests of glucocorticoid
      receptor (GR) function such as the dexamethasone suppression test (DST) are
      frequently abnormal. Neuropsychological impairment is well documented in healthy
      volunteers after administration of glucocorticoids and in patients with bipolar
      affective disorder. This suggests a potential link between neuropsychological and
      hypothalamic-pituitary-adrenal axis function. We examined the hypothesis that
      neuropsychological impairment in bipolar disorder is associated with abnormal GR
      function. METHODS: Seventeen euthymic bipolar patients and 16 controls completed
      tests of verbal declarative and working memory (WM) tests and the DST. The
      correlation between neuroendocrine and neuropsychological function was examined.
      RESULTS: Bipolar patients made significantly more errors of omission and
      commission on the WM paradigm and demonstrated impaired verbal recognition
      memory. Patients' post-dexamethasone cortisol correlated with WM commission
      errors (r(s) = 0.64, p = 0.0006). No such relationship was evident in controls.
      CONCLUSION: Deficits in declarative memory and WM are evident in patients with
      bipolar disorder. The deficit in retrieval accuracy from WM appears to be
      correlated with abnormal GR function.

PMID- 16411986
TI  - Phenomenology associated with age at onset in patients with bipolar disorder at
      their first psychiatric hospitalization.
AB  - OBJECTIVE: To compare the clinical presentation of patients with early-onset (age
      <18 years) and typical-onset (age 20-30 years) bipolar disorder at the time of
      first hospitalization. METHODS: Patients, aged 12-45 years at their first
      psychiatric hospitalization, with a DSM-IV diagnosis of bipolar disorder, manic
      or mixed, were evaluated on measures of manic, depressive, and positive psychotic
      symptoms. Differences in symptom profiles between early- and typical-onset groups
      were examined. RESULTS: One hundred three early-onset and 58 typical-onset
      patients were compared. Mixed episodes were more common in the early-onset group,
      while psychotic features and current substance use were more common in the
      typical-onset group. There was no significant difference in manic symptom
      severity ratings between early- and typical-onset groups (F = 1.8, df = 11, 144,
      p = 0.06). However, these groups differed in depressive (F = 4.2, df = 16, 139, p
      < 0.001) and positive psychotic (F = 2.8, df = 16, 139, p = 0.001) symptom
      profiles. Typical-onset bipolar patients reported more severe weight loss and
      formal thought disorder compared with early-onset patients. CONCLUSIONS:
      Depressive and positive psychotic symptoms may differ in association with age at
      onset among patients with bipolar disorder. Additional studies are necessary to
      determine whether homogeneous phenotypes of bipolar disorder can be delineated
      based upon age at onset.

PMID- 16411987
TI  - Ethnic differences in symptom presentation of youths with bipolar disorder.
AB  - OBJECTIVE: To compare symptom profiles of African-American and white adolescents
      with a diagnosis of bipolar disorder. METHOD: Adolescents, aged 12-18 years at
      their first psychiatric hospitalization, with a DSM-IV diagnosis of bipolar
      disorder, manic or mixed, were evaluated on measures of manic, depressive, and
      positive symptoms of psychosis. Ethnic differences in symptom profiles were
      examined using multivariate analysis of covariance, and specific symptoms
      contributing to the difference were analyzed. RESULTS: Ethnic differences existed
      in manic and positive symptom profiles, but not depressive symptoms. Compared
      with the white cohort, African-American youths were diagnosed more frequently as
      having psychotic features, and had higher ratings for auditory hallucinations.
      CONCLUSIONS: Similar to adults, symptom expression in adolescent bipolar disorder
      may differ between ethnic groups. Future studies are needed to replicate these
      findings and explore possible explanations.

PMID- 16411988
TI  - Conserving fertility in the management of gynaecological cancers.
AB  - The quality of cancer treatment is judged by both morbidity and mortality.
      Patients benefit if morbidity is reduced without compromising mortality. This
      applies particularly for women who develop gynaecological malignancy during their
      childbearing years where curative treatment also renders them infertile. This
      study reviews the increasing role of fertility-sparing surgery in such women. A
      literature search was undertaken using PubMed, entering the terms endometrial
      cancer, cervical cancer and ovarian cancer in conjunction with the terms
      fertility and fertility sparing. Each relevant identified paper was reviewed,
      references checked and results collated to provide an evidence-based summary of
      fertility-sparing treatments for gynaecological malignancy. Fertility-sparing
      surgery is appropriate in many circumstances, and all doctors who advise young
      women with gynaecological malignancy should be aware of these possibilities.
      However, data are relatively sparse in many situations, and careful counselling
      and balanced guidance are essential if patients are to understand the full
      implications of their choices.

PMID- 16411989
TI  - Periodontal disease and adverse pregnancy outcomes: a systematic review.
AB  - BACKGROUND: Recent studies suggest that periodontal disease, as a source of
      subclinical and persistent infection, may induce systemic inflammatory responses
      that increase the risk of adverse pregnancy outcomes. OBJECTIVES: To examine the
      existing evidence on the relationship between periodontal disease and adverse
      pregnancy outcomes. SEARCH STRATEGY: Published studies identified via searches of
      the MEDLINE, EMBASE, CINAHL, and Current Contents full-text databases. SELECTION
      CRITERIA: We identified and selected observational studies (i.e. case-control,
      cross-sectional, and cohort) and nonrandomised controlled studies or randomised
      controlled trials that examined periodontal disease as a risk factor for adverse
      pregnancy outcomes. DATA COLLECTION AND ANALYSIS: Odds ratios (OR) or risk ratios
      (RR) were extracted or calculated from the studies' data. We calculated pooled
      effect size for two clinical controlled trials but not for the observational
      studies due to the heterogeneity in definitions for periodontal disease and
      adverse pregnancy outcomes across studies. MAIN RESULTS: Twenty-five studies (13
      case-control, 9 cohort, and 3 controlled trials) were identified. The studies
      focused on preterm low birthweight, low birthweight, preterm birth, birthweight
      by gestational age, miscarriage or pregnancy loss, and pre-eclampsia. Of the
      chosen studies, 18 suggested an association between periodontal disease and
      increased risk of adverse pregnancy outcome (ORs ranging from 1.10 to 20.0) and 7
      found no evidence of an association (ORs ranging from 0.78 to 2.54). Three
      clinical trial studies suggest that oral prophylaxis and periodontal treatment
      can lead to a 57% reduction in preterm low birthweight (pooled RR 0.43; 95% CI
      0.24-0.78) and a 50% reduction in preterm births (RR 0.5; 95% CI 0.20-1.30).
      AUTHOR'S CONCLUSIONS: Periodontal disease may be associated with an increased
      risk of adverse pregnancy outcome. However, more methodologically rigorous
      studies are needed for confirmation.

PMID- 16411990
TI  - Cost-effectiveness of prophylactic magnesium sulphate for 9996 women with pre
      eclampsia from 33 countries: economic evaluation of the Magpie Trial.
AB  - OBJECTIVE: To assess the cost-effectiveness of using magnesium sulphate for pre
      eclampsia to prevent eclampsia. DESIGN: Multinational trial-based economic
      evaluation. SETTING: Thirty-three countries participating in the Magnesium
      Sulphate for Prevention of Eclampsia (Magpie) Trial. POPULATION: Women (9996)
      with pre-eclampsia from the Magpie Trial. METHODS: Outcome and hospital resource
      use data were available for the trial period from the Magpie Trial. Country
      specific unit costs (U.S. dollar, year 2001) were obtained subsequently from
      participating hospitals by questionnaire. Cost-effectiveness was estimated for
      three categories of countries grouped by gross national income (GNI) into high,
      middle and low GNI countries using a regression model. Uncertainty was explored
      in sensitivity analyses. MAIN OUTCOME MEASURES: Eclampsia, hospital care costs
      and the incremental cost per case of eclampsia prevented. RESULTS: The number of
      women with pre-eclampsia who needed to receive magnesium sulphate to prevent one
      case of eclampsia was 324 [95% confidence interval (CI) 122, infinity] in high,
      184 (95% CI 91, 6798) in middle and 43 (95% CI 30, 68) in low GNI countries. The
      additional hospital care cost per woman receiving magnesium sulphate was $65, $13
      and $11, respectively. The incremental cost of preventing one case of eclampsia
      was $21,202 in high, $2473 in middle and $456 in low GNI countries. Reserving
      treatment for severe pre-eclampsia would lower these estimates to $12,942, $1179
      and $263. CONCLUSIONS: Magnesium sulphate for pre-eclampsia costs less and
      prevents more eclampsia in low GNI than in high GNI countries. Cost-effectiveness
      substantially improves if it is used only for severe pre-eclampsia, or the
      purchase price is reduced in low GNI countries.

PMID- 16411991
TI  - Altered placental syncytin and its receptor ASCT2 expression in placental
      development and pre-eclampsia.
AB  - OBJECTIVE: To investigate the alterations of syncytin, a fusogenic membrane
      protein involved in syncytiotrophoblastic layer formation, and its receptor ASCT2
      expression in placental development and pre-eclampsia. DESIGN: Analyses of
      syncytin and ASCT2 expression in placentas from different stages of pregnancy and
      women with pre-eclampsia and in cytotrophoblasts cultured in normoxic and hypoxic
      conditions. SETTING: Placental samples were collected from a tertiary medical
      centre. POPULATION: Sixteen women with pre-eclampsia and 58 pregnant women
      presented as pregnancy (5-19 weeks of gestation) for elective termination,
      preterm birth, or normal term delivery. METHODS: The quantitative real-time
      polymerase chain reaction was used to study the syncytin and ASCT2 expression
      during placental development in 35 placentas from women without pre-eclampsia
      (ranged from 5 to 40 weeks of gestation) and the alterations of pre-eclamptic
      placentas (n=16) compared with gestational-age-matched controls (n=16). Western
      blot analysis was performed to study the protein level of syncytin in pre
      eclamptic placentas and gestational-age-matched controls. The hypoxic effect on
      trophoblastic syncytin and ASCT2 expression was further studied in
      cytotrophoblasts cultured in 2% oxygen (n= 7). MAIN OUTCOME MEASURES: Syncytin
      and ASCT2 messenger RNA (mRNA) in placental tissue and cytotrophoblasts. RESULTS:
      The level of syncytin mRNA expression increased significantly since the first
      trimester of pregnancy until 37 weeks of gestation, when the level of syncytin
      expression was reduced. The ASCT2 mRNA expression was decreased significantly
      since the second trimester and was relatively stable since then to 40 weeks of
      gestation. Furthermore, a significant reduction in syncytin mRNA expression was
      observed in pre-eclamptic placentas and cytotrophoblasts cultured in hypoxia, but
      not a reduction in ASCT2 mRNA expression. Correlatively, the protein level of
      syncytin was decreased in pre-eclamptic placentas. CONCLUSIONS: A reduced
      placental expression of syncytin but not ASCT2 may contribute to altered
      cytotrophoblastic cell fusion processes and disturbed placental function in pre
      eclampsia. Correspondingly, hypoxia decreases syncytin but not ASCT2 gene
      expression in cultured cytotrophoblasts.

PMID- 16411992
TI  - Decreased maternal lipolysis in intrauterine growth restriction in the third
      trimester.
AB  - OBJECTIVE: Intrauterine growth restriction (IUGR) is a common complication of
      pregnancy. There are many possible aetiologic factors of maternal, placental
      and/or fetal origin. Often there is no known explanation. The aim of this study
      was to investigate whether a reduction in maternal energy substrate production
      could be one of the factors involved in IUGR. DESIGN: Measurement of maternal
      energy substrate production and glucoregulatory hormones in women with growth
      restricted fetuses. SETTINGS: University Hospital, Uppsala, Sweden. POPULATION:
      Ten healthy pregnant women with IUGR were compared with eight recently reported
      healthy women with normal pregnancies. The women were studied at 35.4+/-1.6 weeks
      of gestation after an overnight fast. METHODS: Rates of glycerol and glucose
      production were analysed by gas chromatography/mass spectrometry following
      constant-rate infusion of [1,1,2,3,3-(2)H5]glycerol and [6,6-(2)H2]glucose. MAIN
      OUTCOME MEASURE: Third trimester glycerol and glucose production. RESULTS:
      Glycerol production, reflecting lipolysis, was lower in the women with IUGR than
      in those with normal pregnancies, 2.36+/-0.58 versus 3.06+/-0.66 micromol kg-1
      minute-1 (P=0.033), whereas there was no difference in rate of glucose production
      (glucose production rate [GPR]), 12.1+/-1.5 versus 13.2+/-1.5 micromol kg-1
      minute-1 (P=0.23). Plasma glycerol levels were increased in the women with IUGR
      (P=0.008). CONCLUSIONS: Lipolysis is lower in pregnancies complicated by IUGR as
      compared with normal pregnancies. Increased lipolysis during pregnancy provides
      substrate for maternal energy metabolism, which spares glucose for the fetus. A
      reduced maternal production of energy substrate could be one of several factors
      underlying IUGR. A lack of relationship between insulin levels and either
      lipolysis or GPR suggests defective regulation of energy substrate production in
      this group of pregnant women.

PMID- 16411993
TI  - Comparison of the maternal experience and duration of labour in two upright
      delivery positions--a randomised controlled trial.
AB  - OBJECTIVE: To compare two upright delivery positions at the second stage of
      labour in healthy primiparous women with regard to duration of the second stage
      of labour and maternal experience. DESIGN: A randomised controlled trial.
      SETTING: A county hospital delivery ward. SAMPLE: Primiparous subjects (n=271)
      were randomly allocated to a kneeling (n=138) or a sitting (n=133) position
      during the second stage of labour. A postpartum questionnaire was answered by
      264/271 women (97%) participating in the trial. METHODS: Primiparous subjects
      were randomised to a kneeling or sitting delivery position during second stage of
      labour. Analysis was performed on an intention-to-treat basis. MAIN OUTCOME
      MEASURE: Duration of the second stage of labour. RESULTS: A comparison of the
      duration of the second stage of labour (kneeling 48.5 minutes+/-27.6 SD, sitting
      41 minutes+/-23.4 SD) revealed no significant difference between the groups. A
      sitting position during the second stage of labour was associated with a higher
      level of delivery pain (P<0.01), a more frequent perception of the second stage
      as being long (P=0.002), less comfort for giving birth (P=0.03) and more frequent
      feelings of vulnerability (P=0.05) and exposure (P=0.02). There were no
      significant differences in the frequency of sphincter ruptures although a sitting
      position was associated with a higher degree of postpartum perineal pain
      (P<0.001) (Table 3). CONCLUSIONS: Kneeling and sitting upright during the second
      stage of labour do not significantly differ from one another in duration of the
      second stage of labour. In healthy primiparous women, a kneeling position was
      associated with a more favourable maternal experience and less pain compared with
      a sitting position.

PMID- 16411994
TI  - Does a first trimester dating scan using crown rump length measurement reduce the
      rate of induction of labour for prolonged pregnancy? An uncompleted randomised
      controlled trial of 463 women.
AB  - OBJECTIVE: To evaluate the effect of a first trimester ultrasound dating scan on
      the rate of induction of labour for prolonged pregnancy. DESIGN: Randomised
      controlled trial to include 400 women in each arm of the trial. SETTING:
      Participating general practices and a district general teaching hospital.
      POPULATION: Women attending their general practitioner in the first trimester to
      confirm pregnancy, in whom a first trimester ultrasound scan was not indicated.
      METHODS: Women randomised to the study group (scan group) underwent an ultrasound
      dating scan between 8 and 12 weeks, measuring crown-rump length. The estimated
      date of delivery (EDD) was changed if there was a discrepancy of more than 5 days
      from the gestation, calculated from the last menstrual period (LMP). For the
      remaining women (no-scan group), gestation was determined using the LMP. MAIN
      OUTCOME MEASURES: The rate of induction of labour for prolonged pregnancy.
      RESULTS: Due to circumstances beyond the researchers' control, recruitment was
      abandoned when 463 women had been enrolled. The EDD was adjusted in 13 (5.7%)
      women in the scan group and in 2 (0.9%) in the no-scan group. There was no
      difference in the rate of induction for prolonged pregnancy between the scan (19
      [8.2%]) and the no-scan (17 [7.4%]) groups (relative risk 1.10; 95% CI 0.59
      2.07). CONCLUSIONS: Acknowledging the reduced numbers recruited for study, it is
      concluded that there is no evidence that a first trimester ultrasound dating scan
      reduces the rate of induction of labour for prolonged pregnancy and may result in
      a more expensive healthcare strategy.

PMID- 16411995
TI  - Does training in obstetric emergencies improve neonatal outcome?
AB  - OBJECTIVES: To determine whether the introduction of Obstetrics Emergency
      Training in line with the recommendations of the Clinical Negligence Scheme for
      Trusts (CNST) was associated with a reduction in perinatal asphyxia and neonatal
      hypoxic-ischaemic encephalopathy (HIE). DESIGN: A retrospective cohort
      observational study. SETTING: A tertiary referral maternity unit in a teaching
      hospital. POPULATION: Term, cephalic presenting, singleton infants born at
      Southmead Hospital between 1998 and 2003 were identified; those born by elective
      Caesarean sections were excluded. METHOD: Five-minute Apgar scores were reviewed.
      Infants that developed HIE were prospectively identified throughout this period.
      The study compared the period 'pre-training' (1998-1999), with the period 'post
      training' (2001-2003). MAIN OUTCOME MEASURES: Five-minute Apgar scores and HIE.
      RESULTS: Infants (19,460) were included. Infants born with 5-minute Apgar scores
      of <or=6 decreased from 86.6 to 44.6 per 10,000 births (P<0.001) and those with
      HIE decreased from 27.3 to 13.6 per 10,000 births (P=0.032) following the
      introduction of the training courses in 2000. Antepartum and intrapartum
      stillbirth at term rates remained unchanged, at about 15 and 4 per 10,000 births,
      respectively. CONCLUSION: The introduction of obstetric emergencies training
      courses was associated with a significant reduction in low 5-minute Apgar scores
      and HIE. This improvement has been sustained as the training has continued. This
      is the first time an educational intervention has been shown to be associated
      with a clinically important, and sustained, improvement in perinatal outcome.

PMID- 16411996
TI  - A prospective randomised controlled trial of the Kiwi Omnicup versus conventional
      ventouse cups for vacuum-assisted vaginal delivery.
AB  - OBJECTIVE: To evaluate the performance and safety of the Kiwi Omnicup and compare
      it to conventional vacuum cups in routine clinical practice. DESIGN: A randomised
      controlled trial of the Kiwi Omnicup versus conventional vacuum cups. SETTING:
      Queen Charlotte's and Chelsea Hospital, a tertiary referral hospital in London
      from April 2001 to March 2004. POPULATION: Women requiring assisted vaginal
      delivery by ventouse. METHODS: Women were randomised to the Kiwi Omnicup (n=206)
      or conventional vacuum cups (n=198). Data regarding maternal demographics,
      labour, mode of delivery and maternal and neonatal outcome were collected. MAIN
      OUTCOME MEASURES: Failure of delivery with instrument of first choice. RESULTS:
      The Kiwi Omnicup was less successful at delivery with instrument of first choice
      than the conventional ventouse, failure rate 30.1 versus 19.2% (RR 1.58; 95% CI
      1.10-2.24). It was associated with a greater number of cup detachments (mean 0.68
      compared with 0.28, with 44% compared with 18% having at least one detachment
      [P<0.0001]). There was no difference in the incidence of severe maternal trauma,
      and there were no cases of serious neonatal injury. CONCLUSIONS: The Kiwi Omnicup
      is less successful than conventional ventouse in achieving vaginal delivery, but
      its safety profile is comparable.

PMID- 16411997
TI  - Does the angle of episiotomy affect the incidence of anal sphincter injury?
AB  - OBJECTIVE: Mediolateral episiotomy is associated with lower rates of significant
      perineal tears than midline episiotomy. However, the relationship between precise
      angle of episiotomy from the perineal midline and risk of third-degree tear has
      not been established. This study quantifies this relationship. DESIGN: Case
      control study. SETTING: National Maternity Hospital, Dublin, Ireland. SAMPLE: One
      hundred primiparous women who had undergone right mediolateral episiotomy 3
      months previously. METHODS: Two groups of primiparous women were compared. Cases
      had sustained clinically apparent anal sphincter injury during delivery, while
      controls had not. The angle of episiotomy measured from the midline was marked on
      a superimposed sheet of transparent plastic film and measured using a protractor.
      Data were analysed using Student's t test, chi-square test and logistic
      regression analysis. MAIN OUTCOME MEASURES: Angle of mediolateral episiotomy from
      the perineal midline. RESULTS: Fifty-four cases and 46 controls were assessed.
      Cases were more likely to have undergone assisted delivery and consequently to
      have been delivered by an obstetrician than by a midwife. The mean angle of
      episiotomy measured significantly smaller in cases (30 degrees, 95% CI 28-32
      degrees) than in controls (38 degrees, 95% CI 35-41 degrees; P<0.001). Analysis
      showed a 50% relative reduction in risk of sustaining third-degree tear for every
      6 degrees away from the perineal midline that an episiotomy was cut. CONCLUSIONS:
      These results show that a larger angle of episiotomy is associated with a lower
      risk of third-degree tear and mediolateral episiotomy incisions should be made at
      as large an angle as possible to minimise the risk of sphincter disruption.

PMID- 16411998
TI  - Occult anal sphincter injuries--myth or reality?
AB  - OBJECTIVES: To establish the true prevalence of clinically recognisable and
      occult obstetric anal sphincter injuries (OASIS). DESIGN: Prospective
      interventional study. SETTING: Busy district general hospital. SAMPLE: Two
      hundred and fifty-four women having their first vaginal delivery over a 12-month
      period were invited. Two hundred and forty-one (95%) participated and 208 (86%)
      attended follow up. METHODS: Women had a clinical examination at delivery by the
      accoucheur and repeated by an experienced research fellow immediately after
      delivery. All identified OASIS were verified and repaired by the duty specialist
      registrar or consultant. Endoanal ultrasound was performed immediately postpartum
      prior to suturing and repeated seven weeks later. MAIN OUTCOME MEASURES:
      Prevalence of recognised and occult anal sphincter injuries. RESULTS: Fifty-nine
      (24.5%) women sustained OASIS. The prevalence of OASIS increased significantly
      from 11% to 24.5% when women were re-examined. Of these, 30 occurred in
      deliveries by midwives who missed 26 (87%) and 29 following deliveries by doctors
      who missed 8 (28%) injuries. All clinically apparent OASIS were also identified
      on endoanal ultrasound. In addition, three (1.2%) women had an occult anal
      sphincter injury. Two of these occult sphincter injuries were isolated to the
      internal anal sphincter (IAS) and would not usually be clinically detectable.
      CONCLUSIONS: OASIS occur more frequently than previously reported. Many remain
      undiagnosed and are subsequently classified as occult when identified on anal
      endosonography. Genuine occult injuries are rare. Training in perineal anatomy
      and recognition of OASIS needs to be enhanced in order to increase detection of
      OASIS and minimise the risk of consequent anal incontinence.

PMID- 16411999
TI  - How to repair an anal sphincter injury after vaginal delivery: results of a
      randomised controlled trial.
AB  - OBJECTIVE: To compare two surgical techniques and two types of suture material
      for anal sphincter repair after childbirth-related injury. DESIGN: Factorial
      randomised controlled trial. SETTING: Tertiary referral maternity unit.
      POPULATION: Women with an anal sphincter injury sustained during childbirth.
      METHOD: Women were randomised into four groups: overlap repair with polyglactin
      (Vicryl); end-to-end repair with polyglactin (Vicryl); overlap repair with
      polydioxanone (PDS); and end-to-end repair with PDS. All repairs were completed
      as a primary procedure by staff trained in both methods. MAIN OUTCOME MEASURES:
      Suture-related morbidity at six weeks. Bowel symptoms at 3, 6 and 12 months.
      Anorectal physiology at three months. Quality of life scores at 3 and 12 months.
      RESULTS: One hundred and fifty women (1.5% of deliveries) were eligible and 112
      (75%) were randomised. One hundred and three (92%) attended follow up visit at 6
      weeks, 89 (80%) at 3 months, 79 (71%) at 6 months and 60 (54%) at 12 months. At
      six weeks, there was no difference in suture-related morbidity between groups
      (P=0.11) and 70% patients were completely asymptomatic. Incidence of bowel
      symptoms and quality of life disturbances were low, with no differences between
      the four groups. CONCLUSION: Obstetric anal sphincter repair carried out by
      appropriately trained staff is associated with low morbidity, irrespective of the
      suture material and repair method used.

PMID- 16412000
TI  - New postnatal urinary incontinence: obstetric and other risk factors in
      primiparae.
AB  - OBJECTIVE: To identify obstetric and other risk factors for urinary incontinence
      that occurs during pregnancy or after childbirth. DESIGN: Questionnaire survey of
      women. SETTING: Maternity units in Aberdeen (Scotland), Birmingham (England) and
      Dunedin (New Zealand). POPULATION: A total of 3405 primiparous women with
      singleton births delivered during 1 year. METHODS: Questionnaire responses and
      obstetric case note data were analysed using multivariate analysis to identify
      associations with urinary incontinence. MAIN OUTCOME MEASURES: Urinary
      incontinence at 3 months after delivery first starting in pregnancy or after
      birth. RESULTS: The prevalence of urinary incontinence was 29%. New incontinence
      first beginning after delivery was associated with older maternal age (oldest
      versus youngest group, OR 2.02, 95% CI 1.35-3.02) and method of delivery
      (caesarean section versus spontaneous vaginal delivery, OR 0.28, 95% CI 0.19
      0.41). There were no significant associations with forceps delivery (OR 1.18, 95%
      CI 0.92-1.51) or vacuum delivery (OR 1.16, 95% CI 0.83-1.63). Incontinence first
      occurring during pregnancy and still present at 3 months was associated with
      higher maternal body mass index (BMI>25, OR 1.68, 95% CI 1.16-2.43) and heavier
      babies (birthweight in top quartile, OR 1.56, 95% CI 1.12-2.19). In these women,
      caesarean section was associated with less incontinence (OR 0.39, 95% CI 0.27
      0.58) but incontinence was not associated with age. CONCLUSIONS: Women have less
      urinary incontinence after a first delivery by caesarean section whether or not
      that first starts during pregnancy. Older maternal age was associated with new
      postnatal incontinence, and higher BMI and heavier babies with incontinence first
      starting during pregnancy. The effect of further deliveries may modify these
      findings.

PMID- 16412001
TI  - Persistent urinary incontinence and delivery mode history: a six-year
      longitudinal study.
AB  - OBJECTIVE: To investigate the prevalence of persistent and long term postpartum
      urinary incontinence and associations with mode of first and subsequent delivery.
      DESIGN: Longitudinal study. SETTING: Maternity units in Aberdeen (Scotland),
      Birmingham (England) and Dunedin (New Zealand). POPULATION: Women (4214) who
      returned postal questionnaires three months and six years after the index birth.
      METHODS: Symptom data were obtained from both questionnaires and obstetric data
      from case-notes for the index birth and the second questionnaire for subsequent
      births. Logistic regression investigated the independent effects of mode of first
      delivery and delivery mode history. MAIN OUTCOME MEASURES: Urinary incontinence
      persistent (at three months and six years after index birth) and long term (at
      six years after index birth). RESULTS: The prevalence of persistent urinary
      incontinence was 24%. Delivering exclusively by caesarean section was associated
      with both less persistent (OR=0.46, 95% CI 0.32-0.68) and long term urinary
      incontinence (OR=0.50, 95% CI 0.40-0.63). Caesarean section birth in addition to
      vaginal delivery, however, was not associated with significantly less persistent
      incontinence (OR 0.93, 95% CI 0.67-1.29). There were no significant associations
      between persistent or long term urinary incontinence and forceps or vacuum
      extraction delivery. Other significantly associated factors were increasing
      number of births and older maternal age. CONCLUSIONS: The risk of persistent and
      long term urinary incontinence is significantly lower following caesarean section
      deliveries but not if there is another vaginal birth. Even when delivering
      exclusively by caesarean section, the prevalence of persistent symptoms (14%) is
      still high.

PMID- 16412002
TI  - The prevalence of major abnormalities of the levator ani in urogynaecological
      patients.
AB  - OBJECTIVES: While morphological abnormalities of the pubovisceral muscle have
      been described on magnetic resonance imaging (MRI), their relevance remains
      unclear. This study was designed to define prevalence and clinical significance
      of such abnormalities in urogynaecological patients. DESIGN: Prospective
      observational study. SETTING: Tertiary urogynaecological clinic. POPULATION:
      Three hundred and thirty-eight consecutive women referred for urodynamic
      assessment. METHODS: Participants underwent a clinical assessment, multichannel
      urodynamics and imaging with 3D translabial ultrasound. Blinded offline analysis
      was performed with the software 4D View (GE Kretztechnik, Zipf, Austria). MAIN
      OUTCOME MEASURES: Major morphological abnormalities of the pubovisceral muscle.
      RESULTS: Defects of the pubovisceral muscle were found in 15.4% of parous women.
      They were exclusively anteromedial (uni- or bilateral), only occurred among women
      who had delivered vaginally and were associated with anterior and central
      compartment prolapse (all P<0.001). There was no association with symptoms of
      bladder dysfunction or urodynamic findings. CONCLUSIONS: Major morphological
      abnormalities of the pubovisceral muscle are common in parous urogynaecological
      patients. They are associated with prolapse of the anterior and central
      compartment, but not with symptoms of bladder dysfunction or urodynamic findings.

PMID- 16412004
TI  - Non-invasive first trimester determination of fetal gender: a new approach for
      prenatal diagnosis of haemophilia.
AB  - Ten carriers of haemophilia referred for prenatal diagnosis were offered first
      trimester non-invasive fetal gender determination by ultrasound and analysis of
      free fetal DNA (ffDNA) in maternal plasma in an attempt to reduce the need for an
      invasive diagnostic procedure in female pregnancies. Although repeat testing was
      required in three cases, fetal gender was determined correctly in all cases (four
      females, six males) at a median gestation of 12(+3) (11(+2) to 14(+1)) using both
      methods. In all cases of a female fetus, the mothers opted not to have invasive
      testing. Both methods provide a reliable option of avoiding invasive testing in
      female pregnancies.

PMID- 16412003
TI  - Computer interviewing in urogynaecology: concept, development and psychometric
      testing of an electronic pelvic floor assessment questionnaire in primary and
      secondary care.
AB  - OBJECTIVE: To develop and evaluate a Web-based, electronic pelvic floor symptoms
      assessment questionnaire (e-PAQ)1 for women. DESIGN: A cross-sectional study in
      primary and secondary care. SETTING: Two general practices, two community health
      clinics and a secondary care urogynaecology clinic. SAMPLE: A total of 432 women
      (204 in primary care and 228 in secondary care) were recruited between June 2003
      and January 2004. METHODS: The e-PAQ was located on a workstation (computer,
      touchscreen and printer). Women completed the e-PAQ prior to their appointment.
      Untreated women in primary care were asked to return seven days later to complete
      the e-PAQ a second time (test-retest). MAIN OUTCOME MEASURES: Factor analysis,
      reliability, validity, patient satisfaction, completion times and system costs.
      RESULTS: In secondary care, factor analysis identified 14 domains within the four
      dimensions (urinary, bowel, vaginal and sexual symptoms) with internal
      consistency (Cronbach's alpha)>or=0.7 in 11 of these. In primary care, alpha
      values were all>or=0.7 and test-retest analysis found acceptable intraclass
      correlations of 0.50-0.95 (P<0.001) for all domains. A measure of face validity
      and utility was gained using a nine-item questionnaire, which yielded strongly
      positive patient views on relevance and acceptability. CONCLUSIONS: The e-PAQ
      offers a user-friendly clinical tool, which provides valid and reliable data. The
      system offers comprehensive symptoms and quality of life evaluation and may
      enhance the clinical episode as well as the quality of care for women with pelvic
      floor disorders.

PMID- 16412005
TI  - Successful pregnancy after an arterial switch procedure for complete
      transposition of the great arteries.

PMID- 16412006
TI  - Re: Are mediolateral episiotomies actually mediolateral?

PMID- 16412008
TI  - Re: Customised birthweight centiles predict SGA pregnancies with perinatal
      morbidity.

PMID- 16412009
TI  - Re: Malaria in pregnancy.

PMID- 16412011
TI  - Re: The use of levonorgestrel-releasing intrauterine system for the treatment of
      menorrhagia in women with inherited bleeding disorders.

PMID- 16412012
TI  - Subarachnoid haemorrhage: more than meets the eye.

PMID- 16412013
TI  - Acute lymphoblastic leukaemia presenting as vasculitis.

PMID- 16412014
TI  - Novel therapeutic strategies targeting growth factor signalling cascades in
      multiple myeloma.
AB  - Multiple myeloma (MM) remains largely incurable despite conventional and high
      dose therapies, and novel biologically based treatment approaches are urgently
      required. Recent studies demonstrate that various growth factors including
      interleukin (IL)-6, insulin-like growth factor (IGF)-1, vascular endothelial
      growth factor (VEGF), the tumour necrosis factor (TNF) family proteins, Wnt, and
      Notch family members play an important role in MM pathogenesis, and mediate
      tumour cell proliferation, drug resistance and migration in the bone marrow (BM)
      milieu. Targeting growth factors, therefore, represents a promising therapeutic
      strategy in MM. Novel agents inhibiting growth factor signalling cascades can
      target ligands, receptors, and/or downstream signalling cascade proteins in MM
      cells and the BM microenvironment. Combinations of these novel agents with
      conventional therapies may not only enhance cytotoxicity, but also avoid drug
      resistance and thereby improve patient outcome in MM.

PMID- 16412015
TI  - The role of gemtuzumab ozogamicin in acute leukaemia therapy.
AB  - Gemtuzumab ozogamicin (GO) is an immunoconjugate that binds to CD33 on the
      surface of acute myeloid leukaemia (AML) blasts and, after internalisation,
      releases a cytotoxic drug, calicheamicin. GO is approved by the US Food and Drug
      Administration for the treatment of CD33-positive AML at first relapse in
      patients 60 years and older who are not candidates for other cytotoxic therapy.
      GO as a single agent has low antileukaemic activity. When given to patients
      meeting the criteria noted above, it produces a complete response (CR) rate of
      only 12%, with another 12% achieving CR with inadequate platelet recovery (CRp).
      The median survival of patients treated with GO monotherapy is 11.2 months. GO
      therapy at 9 mg/m(2) is complicated with hepatic veno-occlusive disease in 5-10%
      of patients, particularly prior to or following stem cell transplantation. GO at
      lower doses combined with chemotherapy as induction or postremission therapy is
      promising, however, and phase III trials are ongoing. GO is probably most active
      in acute promyelocytic leukaemia (APL). It is used for induction regimens in high
      risk APL and for the elimination of minimal residual APL. Case reports suggest
      that GO also has activity in CD33-positive acute lymphoblastic leukaemia. In
      conclusion, single agent GO can induce responses in patients with CD33-positive
      AML in first recurrence. The future of GO is its use in combination with other
      cytotoxic agents. Ongoing clinical trials may better define the role of GO
      combinations, particularly in untreated AML.

PMID- 16412016
TI  - Guidelines on the diagnosis and management of multiple myeloma 2005.

PMID- 16412018
TI  - Analysis of the intraclonal diversity of HLA-A0201-restricted T lymphocyte
      epitopes in follicular lymphoma idiotype.
AB  - Lymphoma-derived immunoglobulin idiotype (Id) is a tumour-specific antigen used
      for antitumour vaccination in follicular lymphoma (FL). However, FL Ids are
      subject to hypermutation and subclones may escape antitumour cytotoxic T-cell
      response. To investigate the intraclonal epitope diversity, we sequenced the FL
      heavy chain gene (consensus Id gene) and subclones of 24 patients. The derived
      polypeptide sequences were analysed by bioinformatics for human leucocyte antigen
      (HLA)-A0201-restricted epitope prediction. Epitopes were classified according to
      BIMAS and SYFPEITHI scores. Surprisingly in these highly mutated polypeptides,
      the epitopes concentrated in short hotspots in the conserved framework regions
      (FRs), both in HLA-A0201(+) and HLA-A0201(-) patients. Similar hotspots have been
      observed by others in chronic lymphocytic leukaemia Ids which in contrast to FL
      have low mutation frequency. FR3 amino acids 78-88 displayed the best-score
      epitopes in Ids containing a VH3-family segment, the most represented in FL Ids.
      Such VH3-FR3(78-88) epitopes were previously demonstrated as immunogenic.
      Modifications of the epitope pattern in subclones of HLA-A0201(+) patients were
      generally absent from high-score peptides, including VH3-FR3(78-88) epitopes (83%
      unmodified). Therefore, no tendency for loss of HLA-A0201-restricted epitopes was
      evidenced and, given their limited intraclonal diversity, VH3-FR3(78-88) epitopes
      may provide a useful target for the induction of cytotoxic response in Id
      vaccinated FL patients.

PMID- 16412017
TI  - Differential immune effects mediated by Toll-like receptors stimulation in
      precursor B-cell acute lymphoblastic leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy and,
      although current therapy is widely effective, relapse remains a significant
      clinical problem for which new treatment strategies are required. The ligation of
      Toll-like receptors (TLR) on antigen-presenting cells stimulates the generation
      of strong T-cell helper type 1 (Th1) adaptive immune responses. Although TLR9
      ligation has been shown to enhance immunogenicity of a number of leukaemia cell
      types, there have been few reports of the effects mediated through other TLR. In
      this study we analysed both the expression of TLR by B-cell precursor ALL cell
      lines and the effects of individual TLR ligation on the ability of ALL cells to
      stimulate allogeneic T cells. While ligation of TLR2, TLR 7 and TLR9 led to
      detectable changes in ALL costimulatory molecule expression, only TLR2 and TLR9
      stimulation influenced T-cell responses. The TLR2 ligand Pam3CysSerLys4 provoked
      the most significant changes in T-cell response, dramatically augmenting
      interferon-gamma production. These results suggest that TLR ligands, in addition
      to TLR9 agonists, may provide a strategy to enhance the generation of anti-ALL
      immune activity by skewing responding T cells towards a Th1 response.

PMID- 16412019
TI  - The involvement of osteopontin and its receptors in multiple myeloma cell
      survival, migration and invasion in the murine 5T33MM model.
AB  - Multiple myeloma (MM) is a malignancy characterised by the accumulation of
      monoclonal plasma cells in the bone marrow. Different reports indicate the
      expression of CD44 variant isoforms (CD44v) by MM cells. Osteopontin (OPN), which
      is expressed by MM cells, is known to be a ligand for CD44v6. In this study, we
      investigated the role of OPN with emphasis on a functional correlation between
      OPN and CD44v in the 5T33MM model. Our group reported the expression of CD44v by
      5T33MM cells. Using this model, we have demonstrated the secretion of OPN by
      5T33MM cells. OPN affected 5T33MM cell survival by increasing proliferation and
      inhibiting apoptosis. OPN also stimulated 5T33MM cell migration, transendothelial
      migration and matrix metalloproteinase-9 activity. We confirmed the proliferative
      and migratory effects of OPN on human MM cells. By applying inhibiting anti
      CD44v6 antibodies, we found that OPN stimulated cell proliferation by engaging
      this isoform. Anti-CD44v antibodies and RGD peptides both inhibited cell
      migration, suggesting an involvement of both, CD44v isoforms and integrins. In
      conclusion, OPN may act as a mediator of MM cell survival by engaging CD44v. The
      protein is further involved in migration and invasion of MM cells through the
      activation of either alphavbeta3 integrin or CD44v isoforms.

PMID- 16412020
TI  - Role of prospective screening of blood for invasive aspergillosis by polymerase
      chain reaction in febrile neutropenic recipients of haematopoietic stem cell
      transplants and patients with acute leukaemia.
AB  - Guidelines for the use of polymerase chain reaction (PCR)-based assays to aid the
      diagnosis of invasive aspergillosis (IA) in high-risk haematology patients have
      not been formulated. We prospectively evaluated a nested PCR assay to detect
      Aspergillus in blood during 95 febrile neutropenic episodes, in patients with
      haematological malignancy and haematopoietic stem cell transplant (HSCT)
      recipients. PCR results were correlated with the diagnostic classification of the
      2002 European Organisation for Research and Treatment of Cancer/Mycosis Study
      Group. When two-positive results were used to define an episode as 'PCR
      positive', the sensitivity, specificity, positive-predictive value and negative
      predictive value for 'proven'/'probable' IA (n = 13) were 100%, 75.4%, 46.4% and
      100%, respectively. Consecutive positive results occurred in 61.5% of these 13
      episodes. Overall, PCR positivity preceded standard diagnosis by a mean of 14 d
      and the median time between positive results was shorter than that in other
      categories of IA. All 13 episodes occurred in the setting of allogeneic HSCT
      recipients and acute leukaemia. If 'eligibility' for antifungal therapy were
      based on two-positive-PCR tests, use of empiric treatment could have been reduced
      by up to 37%. The nested PCR assay is a practical screening test for excluding
      IA. Patients with consecutive positive results or intermittent-positive results
      (within 14 d) warrant immediate investigations for IA and the initiation of
      antifungal therapy.

PMID- 16412021
TI  - Autoantibodies to thrombin directed against both of its cryptic exosites.
AB  - Immunoglobulin G (IgG) anti-thrombin autoantibodies (ATA) were purified from the
      plasma of a patient referred for haematological investigation because of bleeding
      for 24 h following a dental extraction. The ATA did not inhibit the catalytic
      activity of thrombin against a chromogenic substrate, suggesting that they did
      not interact with the active site of thrombin. The ATA did, however, prolong the
      time required to generate thrombin in plasma, suggesting that they inhibited
      factor V and factor VIII activation. Surface plasmon resonance (SPR) was used to
      demonstrate that ATA bound to thrombin with high affinity. Competition of
      thrombin-ATA binding, using known thrombin exosite I and II ligands (hirudin,
      thrombomodulin and heparin), demonstrated that ATA bound to both thrombin
      exosites. Thrombin residues that are important for ATA binding were identified
      using a library of 53 recombinant thrombin variants encompassing alanine
      substitutions of 78 surface-exposed residues. They were H66, R68, R70 and Y71 in
      exosite I, and R89, R93, E94, R98, R245 and K248 in exosite II. ATA bound
      predominantly to exosite II. They did not bind to prothrombin, illustrating the
      cryptic nature of both exosites exposed and presented as potential antigens
      following prothrombin conversion to thrombin.

PMID- 16412022
TI  - The impact of genetic variation in the region of the GPIIIa gene, on Pl
      expression bias and GPIIb/IIIa receptor density in platelets.
AB  - Some studies have suggested that genetic variability in the glycoprotein (GP)
      IIIa gene modulates expression of platelet GPIIb/IIIa (alpha(2b)beta(3)). We
      sought to determine as to whether combinations of genetic variants within the
      GPIIIa gene (haplotypes) influenced the expression of GPIIIa RNA and protein
      levels in human platelets. Three promoter polymorphisms, Pl(A1/A2) genotype and
      platelet receptor densities were determined in 207 acute coronary syndrome (ACS)
      patients. Allele-specific quantitative reverse transcription-polymerase chain
      reaction of platelet RNA from Pl(A1/A2) heterozygotes identified a greater
      expression of Pl(A2) bearing transcripts among heterozygotes. Among the patients
      studied, the ratio of Pl(A1)/Pl(A2) RNA expression was significantly influenced
      by promoter haplotype (P < 0.01). However, this effect reflected carriership of
      rare not common haplotypes (P = 0.2). There was a threefold variation between
      subjects in the number of GPIIb/IIIa receptors expressed per platelet, although
      no association between receptor density and the Pl(A2) (P = 0.93) or promoter
      polymorphisms was demonstrated (-468A, P = 0.52; -425C, P = 0.59; -400A, P =
      0.52). Among common haplotypes, Pl(A1)/Pl(A2) RNA expression was negatively
      correlated with adjusted GPIIb/IIIa receptor density (P = 0.04). The overall
      trend towards higher expression of Pl(A2) bearing message in Pl(A1/A2)
      heterozygotes, and the existence of rare haplotypes with more pronounced changes
      indicate the existence of cis-acting genetic factors that remain to be
      identified.

PMID- 16412023
TI  - Inhibition of the phosphatidylinositol-3 kinase/Akt promotes G1 cell cycle arrest
      and apoptosis in Hodgkin lymphoma.
AB  - Activation of the phosphatidylinositol 3-kinase (PI(3)K) pathway has been linked
      with tumour cell growth, survival and resistance to therapy in several cancer
      types. The active, phosphorylated form of Akt (pAkt) was found to be aberrantly
      expressed in Hodgkin lymphoma (HL)-derived cell lines and in Hodgkin-Reed
      Sternberg (HRS) cells in 27 of 42 (64.3%) of primary lymph node sections of HL,
      indicative of PI(3)K activity. Akt phosphorylation was not associated with loss
      of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression,
      but with its phosphorylation in HL-cell lines, suggesting that its biological
      function is impaired. Akt phosphorylation was further induced by CD30 ligand
      (CD30L), CD40L and receptor activator of nuclear factor kappa B (RANK) ligand.
      The PI(3)K inhibitor LY294002 demonstrated antiproliferative effects in a dose-
      and time-dependent manner, which was associated with Akt dephosphorylation on
      Thr308 and Ser473 sites and dephosphorylation of the downstream ribosomal protein
      S6. LY209002 induced cell cycle arrest in the G0/G1 phase and apoptosis, which
      were associated with upregulation of MDM2, downregulation of cyclin D1,
      activation of caspase 9 and poly-ADP-ribose polymerase cleavage. The Akt
      inhibitor QLT394 also demonstrated antiproliferative effects in a dose- and time
      dependent manner, dephosphorylated ribosomal S6 and cleaved caspase 9.
      Collectively, these data suggest that the aberrant activation of the PI(3)K/Akt
      survival pathway in HRS cells is not because of loss of PTEN expression. Our data
      suggest that PTEN phosphorylation and activation of CD30, CD40 and RANK may play
      a role in activating Akt in HRS cells.

PMID- 16412024
TI  - Histamine increases sickle erythrocyte adherence to endothelium.
AB  - Complications of sickle cell anaemia include vascular occlusion triggered by the
      adherence of sickle erythrocytes to endothelium in the postcapillary venules.
      Adherence can be promoted by inflammatory mediators that induce endothelial cell
      adhesion molecule expression and arrest flowing erythrocytes. The present study
      characterised the effect of histamine stimulation on the kinetics of sickle cell
      adherence to large vessel and microvascular endothelium under physiological flow.
      Increased sickle cell adherence was observed within minutes of endothelial
      activation by histamine and reached a maximum value within 30 min. At steady
      state, sickle cell adherence to histamine-stimulated endothelium was 47 +/- 4
      adherent cells/mm(2), 2.6-fold higher than sickle cell adherence to unstimulated
      endothelial cells. Histamine-induced sickle cell adherence occurred rapidly and
      transiently. Studies using histamine receptor agonists and antagonists suggest
      that histamine-induced sickle cell adhesion depends on simultaneous stimulation
      of the H(2) and H(4) histamine receptors and endothelial P-selectin expression.
      These data show that histamine release may promote sickle cell adherence and vaso
      occlusion. In vivo histamine release should be studied to determine its role in
      sickle complications and whether blocking of specific histamine receptors may
      prevent clinical complications or adverse effects from histamine release
      stimulated by opiate analgesic treatment.

PMID- 16412025
TI  - Two new phosphoglycerate kinase mutations associated with chronic haemolytic
      anaemia and neurological dysfunction in two patients from Spain.
AB  - We report two previously undescribed mutations of the phosphoglycerate kinase
      gene (PGK1) leading to enzyme deficiency. In both cases, the patients were of
      Spanish origin and they exhibited a severe life-long chronic haemolytic anaemia
      associated with progressive neurological impairment. Sequence analysis of the
      first patient's entire PGK1 gene found a novel missense mutation (140T > A). This
      mutation caused an amino acid change of Ile to Asn at 46th position from the
      NH(2)-terminal serine residue (Ile46Asn), which has been called PGK-Barcelona
      based on the place of origin of the patient. In the second patient, a G to A
      transversion was discovered at nucleotide 958 (958G > A). This caused a Ser319Asn
      amino acid substitution. Since this mutation had not been previously described,
      the provisional name of PGK-Murcia was given to this deficient enzyme. The
      crystal structure of porcine PGK was used as a molecular model to investigate how
      these mutations may affect enzyme structure and function. In both cases, the
      mutations did not modify any of the PGK binding sites for ATP or 3PG, so their
      consequence is related to a loss of enzyme stability rather than a decrease of
      enzyme catalytic function.

PMID- 16412026
TI  - Vascular endothelial growth factor and platelets in primary (essential)
      thrombocythaemia.

PMID- 16412027
TI  - Preventing ABO incompatible blood transfusion.

PMID- 16412030
TI  - Chemoprevention of colorectal cancer with nonsteroidal anti-inflammatory drugs.
AB  - Colorectal carcinoma is one of the commonest solid organ tumors in the world and
      its prevalence appears to be increasing in Asia. Recently, there has been much
      interest in various chemotherapeutic agents for the management of this condition,
      in particular nonsteroidal anti-inflammatory drugs (NSAIDs). There is a large
      amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase
      (COX)-2 selective inhibitors such as rofecoxib and celecoxib, have a role in the
      setting of primary and secondary prevention, and adjuvant therapy of both
      sporadic colorectal carcinoma and familial adenomatous polyposis. This review
      examines some of this data, as well as the potential problems and limitations of
      using these agents, particularly in light of the recent withdrawal of rofecoxib.

PMID- 16412031
TI  - Pathogenesis of nonalcoholic steatohepatitis (NASH).
AB  - Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver diseases
      that range from hepatic steatosis at the most clinically benign end of the
      spectrum, through an intermediate lesion, nonalcoholic steatohepatitis (NASH), to
      cirrhosis at the opposite extreme. Epidemiology studies have estimated that about
      20-30% of adults in the United States and other Western countries have NAFLD, and
      of these about 10% (2-3% of adults) meet the diagnostic criteria of NASH. Studies
      of animals and humans with obesity-related fatty liver disease have revealed much
      about the mechanisms that mediate this common pathology. The pathogenesis of NASH
      is multifactorial and includes insulin resistance, excessive intracellular fatty
      acids, oxidant stress, mitochondrial dysfunction and the role of innate immunity.
      This review will briefly discuss the epidemiology of NAFLD and focus on current
      understanding of the pathogenesis of NASH.

PMID- 16412032
TI  - Combined histology and molecular biology for diagnosis of early stage gastric
      MALT lymphoma.
AB  - OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa
      associated lymphoid tissue (MALT) lymphoma and provide evidence for selected
      optimal cases to be treated in the early stage. METHODS: Thirty-one cases of
      gastric lymphoid hyperplasia (GLH) were selected and multiple investigations
      including histology, protein level, DNA and chromosome levels, combined with
      clinical follow-up were performed. Histological grade was according to Isaacson's
      criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (kappa), anti-lambda (lambda)
      and Ki-67 were used for immunohistochemical staining; semi-nested polymerase
      chain reaction (PCR) was used to detect IgH gene rearrangement and reverse
      transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome
      translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy
      for Helicobacter pylori. Changes in histological grade, endoscopic appearance,
      expression of Ki-67 and IgH gene rearrangement were compared after eradication
      treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and
      gastric ulcer most were histological grade 2 and 3. Only one case had lambda
      light chain restriction and 10 cases had monoclonal IgH gene rearrangement.
      Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly
      increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2
      MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course
      of treatment had to be given in 4 cases. All cases were followed up for 1.5-37
      months. Of the 27 successful eradication cases, 18 showed complete regression
      both histologically and endoscopically, 4 had partial regression and 7 were
      unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology,
      expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1
      fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the
      best treatment strategy.

PMID- 16412033
TI  - Gastric distention enhances FOS and calcitonin gene-related peptide expression in
      the spinal cord and brain of rats.
AB  - OBJECTIVE: The purpose of this study was to determine the pathway and mode of
      transmission of visceral stimuli by investigating the distribution of the FOS and
      calcitonin gene-related peptide (CGRP) proteins in the central nervous system.
      METHODS: Twenty-four Sprague-Dawley rats were divided into three groups: study
      group (n = 12), sham control group (n = 6), and normal control group (n = 6). A
      balloon was implanted into the stomach of the rats in the study and sham control
      groups. After 48 h, the rats in the study group had the stomach distended (80
      mmHg) for 2 h, after which they were killed and the antrum, thoracic spinal cord
      and brain were isolated or dissected. The expression of Fos and CGRP in these
      tissues was detected immunohistochemically. RESULTS: FOS expression in the dorsal
      horn of the spinal cord, dorsal nucleus of the vagal nerve, nucleus of the
      solitary tract in the study rats was significantly higher than in the sham and
      normal controls. However, no difference was found between the three groups in FOS
      expression in the myenteric plexus. Similarly, gastric distention enhanced CGRP
      expression significantly in the spinal cord and medulla oblongata and correlated
      closely with FOS expression in these two areas. CONCLUSIONS: Gastric distention
      can activate the limbic system, and CGRP plays an important role in the input of
      visceral stimuli.

PMID- 16412034
TI  - Appropriateness of colonoscopy using the ASGE guidelines: experience in a large
      Asian hospital.
AB  - BACKGROUND: The is currently a heavy burden on endoscopy services worldwide and
      although guidelines for the appropriate use of esophagogastroduodenoscopy (EGD)
      have been well studied, there are few such studies with respect to colonoscopy
      and none for the Asia-Pacific region. This study aimed, firstly, to determine the
      'appropriateness of colonoscopy' for procedures performed in the endoscopy unit
      of a large Asian hospital using the American Society of Gastrointestinal
      Endoscopy (ASGE) 2000 guidelines, and secondly, to determine predictive factors
      including 'appropriateness of colonoscopy' for positive findings and colorectal
      cancer (CRC). METHODS: A prospective cross-sectional study was carried out on
      consecutive colonoscopies performed in the University of Malaya Medical Center.
      The unit has an open-access endoscopy policy for doctors who work in the
      hospital. Referrals were from endoscopists (gastroenterologists and surgeon
      endoscopists), primary care physicians and other specialists. The indication of a
      procedure referral was recorded and judged 'appropriate' or 'inappropriate' using
      the ASGE criteria. The colonoscopic findings were recorded and classified as
      positive (endoscopies showing any pathology that had direct therapeutic or
      prognostic consequences) or negative findings (endoscopies showing no pathology
      or minor pathologies). Predictive factors for positive findings and CRC were
      determined using multivariate analysis. RESULTS: Of 380 patients referred for
      colonoscopy, 220 (57.9%) were classified as appropriate according to the ASGE
      guidelines, and 49 (12.9%) as inappropriate. The remaining 111 patients (29.2%)
      presented with complaints and conditions that could not be categorized. The rate
      of appropriate referral was similar for all three categories of physician
      (endoscopists: 59.8%, primary care physicians: 48.1%, others: 51.1%). When
      referrals by endoscopists were substratified according to gastroenterologists and
      surgeon-endoscopists, the rate of appropriate referral among gastroenterologists
      (78.4%) was significantly higher than that of surgeon-endoscopists (56.1%) (P =
      0.049), primary care physicians (P = 0.013) and 'others' (P = 0.009). The most
      common appropriate indications were unexplained Rectalbleeding (79 cases, 20.8%)
      followed by CRC surveillance (45 cases, 11.8%). The most common inappropriate
      indication was inappropriately timed colonic cancer surveillance (32 cases,
      8.4%). Chronic constipation in 36 cases (9.5%) was the most common 'unlisted'
      indication. A positive colonoscopic finding was detected in 131 (34.5%)
      examinations and CRC was found in 36 patients (9.5%). Appropriateness of
      indication was not a predictive factor for positive findings or CRC and there was
      no difference in the proportion of cases with positive findings or CRC in the
      three 'appropriateness categories'. Multivariate analysis revealed that only
      Rectalbleeding and smoking were significant independent positive predictive
      factors for positive findings and CRC. CONCLUSION: The appropriateness of
      colonoscopy was not high among the different sources of referrals except for the
      subgroup of 'gastroenterologist'. Furthermore, the rates of positive findings and
      CRC among the cases with appropriate, inappropriate and unlisted indications did
      not differ. The ASGE guidelines will need to be modified for Asia to be of
      practical use.

PMID- 16412035
TI  - Preventive strategy for Candida gut translocation during ischemia-reperfusion
      injury supervening on protein-calorie malnutrition.
AB  - OBJECTIVE: The aim of the present study was to test the hypothesis that protein
      calorie malnutrition aggravates the gut translocation of Candida albicans
      triggered by mesenteric ischemia-reperfusion (IR) injury in an experimental model
      while testing a natural product containing the antifungal anethole/polygodial
      mixture (Kolorex). METHODS: MFI strain white mice (n = 90) were randomly
      allocated to a 4-week dietary regimen: (1) standard pellet diet containing 25%
      casein; (2) low-protein (2.5%) casein diet; (3) as group 2 plus oral
      supplementation with 20 microL of a 5% solution of Kolorex during the last 4
      days. Twenty rats from each of these groups (termed 1a, 2a and 3a) were orally
      inoculated with Candida suspension 6 h prior to mesenteric IR injury. Animals of
      each group but without Candida inoculation (termed 1b, 2b and 3b) served as
      control. A colon permeability study was carried out as well. Rats were killed
      prior to the IR injury and 3 h afterwards. Control rats were killed at the same
      time. RESULTS: Over 60% of the mesenteric lymph nodes and 30% of kidney samples
      were positive for C. albicans in the low-protein-fed rats after IR injury.
      Kolorex significantly decreased that rate of positivity and also significantly
      reduced the concentration of C. albicans per gram of each positive tissue sample
      examined. Protein-calorie malnourished animals showed a statistically significant
      increase in colon permeability and this phenomenon further increased after IR
      injury. The groups of rats treated with Kolorex compound showed a partial,
      although significant, improvement of this parameter. CONCLUSIONS: These results
      suggest that Kolorex might exert a competitive effect against with C. albicans
      colonization. The present study represents the first experimental in vivo
      investigation of the anethole/polygodial-containing compound under the specific
      conditions of calorie-protein malnutrition and the results have potential
      clinical interest.

PMID- 16412036
TI  - Serous cystic neoplasms of the pancreas: a clinicopathologic and
      immunohistochemical analysis.
AB  - OBJECTIVE: To clarify whether the various subtypes of serous cystic neoplasms
      (SCNs) of the pancreas can be distinguished from each other by marker profiles.
      METHODS: The immunoprofiles of 13 SCNs were defined by using antibodies against
      cytoskeletal, neuroendocrine, hormone receptor, and mucin markers. In addition,
      we examined the expression of calrentinin and alpha-inhibin. RESULTS: SCN
      included 7 cases of serous microcystic adenomas (SMA), 3 cases of serous
      oligocystic ill-defined adenomas (SOIA), 1 case of solid serous adenoma (SSA), 1
      case of von Hippel-Lindau-associated cystic neoplasm (VHL-CN), and 1 case of
      serous cystadenocarcinoma (SCC). These neoplasms are histologically similar, but
      differ in their localization, gross appearance, gender distribution, and
      biological behavior. The various types of SCNs showed a very similar
      immunoprofile, characterized by positivity for cytokeratins (100%) and negativity
      for vimentin and synaptophysin. Other markers that were commonly expressed in the
      SCNs were alpha-inhibin (85%), MUC1 (69%) and MUC6 (77%). CONCLUSION: The results
      suggest that, despite their biologic differences, the various types of SCNs have
      the same (or a very similar) cell type and may therefore have a common direction
      of differentiation. A centroacinar origin is supported by the finding that a
      number of SCNs share MUC1 and MUC6 expression with pancreatic centroacinar cells.
      Alpha-inhibin, and MUC6 may be regarded as new markers for this type of
      pancreatic tumor.

PMID- 16412037
TI  - Prospective randomized clinical trial of two drug delivery pathway in the
      treatment of inoperable advanced pancreatic carcinoma.
AB  - OBJECTIVES: Evaluate the effect of an implanted percutaneous left subclavian
      artery port-catheter drug delivery system for regional chemotherapy of inoperable
      pancreatic carcinoma. METHODS: One hundred and forty patients with inoperable
      pancreatic carcinoma were enrolled and randomized into two groups to receive the
      FAM regimen on a 6-day cycle at 1-month intervals: 70 patients in the regional
      interventional chemotherapy group in which treatment was infused directly into
      the common hepatic artery, and 70 patients who received the same chemotherapy
      regimen via the peripheral vein. RESULT: In the interventional chemotherapy
      group, there were 5 cases of complete remission (CR) and 49 cases of partial
      remission (PR), giving a response rate (CR+PR) of 77.1%; pain control was
      effective in 95.7% cases; survival time was 3-34 months (median 13.5). There was
      no case of CR in the systemic chemotherapy group, and 25 cases of PR, giving a
      response rate of 35.7%; pain control was effective in 35.7%, and survival time
      was 1-13 months (median 6.2). The differences between the two groups in response
      rate and survival were statistically significant (P < 0.005). Nausea and vomiting
      occurred in 48.6% of the interventional chemotherapy group and 41.3% of the
      systemic chemotherapy group (NS). There were three cases of serious
      myelosuppression in the systemic chemotherapy group and one case died. There was
      a significant difference between the two groups in white blood cell count after
      the chemotherapy, indicating that the myelosuppressive effect was serious in the
      systemic chemotherapy group. CONCLUSION: Interventional arterial infusion
      chemotherapy could significantly improve quality of life and prolong the survival
      of patients with inoperable pancreatic carcinoma.

PMID- 16412038
TI  - Meta-analysis of inoperable pancreatic cancer: gemcitabine combined with
      cisplatin versus gemcitabine alone.
AB  - OBJECTIVES: To compare the therapeutic effects of gemcitabine (GEM) monotherapy
      with GEM-cisplatin (DDP) combination chemotherapy in patients with advanced stage
      pancreatic cancer (APCa) through meta-analysis. METHODS: MEDLINE and EMBASE
      searches were supplemented by information from trial registers of randomized
      controlled trials (RCTs) for GEM-DDP combination chemotherapy and GEM alone in
      APCa. A quantitative meta-analysis using updated information based on inclusion
      criteria from all available RCTs was carried out by two reviewers. The primary
      meta-analysis involved the overall survival (OS), objective remission rate (ORR)
      and toxicity. RESULTS: The meta-analysis included six RCTs. There was no
      significant advantage for the GEM-DDP combination group in 6-month survival rate
      (P = 0.24) or clinical benefit rate (P = 0.58). There was a marginal significant
      improvement for the GEM-DDP combination group in ORR (RD = 6%, P = 0.05; RD, risk
      difference = risk in the GEM-DDP combination group - risk in the GEM alone
      group). Moreover, there was a significant improvement for the combination group
      in 6-month TTP/TTF (RD = 9%, P = 0.02). WHO grade 3-4 toxicity was higher for the
      GEM-DDP combination group in terms of neutropenia (RD = 6%, P = 0.08),
      thrombocytopenia (RD = 8%, P = 0.17) and vomiting/nausea (RD = 11%, P = 0.07);
      none reached significant difference. CONCLUSION: GEM-DDP combination should not
      be recommended and GEM monotherapy remains the standard treatment for patients
      with APCa.

PMID- 16412039
TI  - Prevalence and risk factors of Helicobacter pylori infection in healthy
      schoolchildren.
AB  - OBJECTIVE: Data regarding the prevalence of Helicobacter pylori infection and its
      potential risk factors among schoolchildren from the Middle East is scarce.
      METHODS: An enzyme-linked immunosorbent assay was used to investigate H. pylori
      status in four groups of children: The first and second groups, 50 children each
      (25 boys, 25 girls) included children from high socioeconomic class (group 1 = 6
      years old; group 2 = 9 years old). The third and fourth groups were sex- and age
      matched, but from low socioeconomic class. To evaluate the association between
      the seroprevalence of H. pylori and selected risk factors, odds ratios (crude and
      adjusted) were calculated using multiple regression analysis. RESULTS: Overall
      seroprevalence rate was 55.5%. Seropositivity was 42%, 52%, 60%, and 68% for
      groups 1, 2, 3, and 4, respectively. Age and sex were not significantly
      associated with H. pylori seropositivity. In the final logistic regression model,
      which was adjusted for age and sex, the following risk factors were found to be
      significantly associated with seropositivity: living in rural areas (P = 0.015),
      poor sanitation (P < 0.001), overcrowding (P = 0.014), low maternal educational
      level (P = 0.010) and low socioeconomic status (P = 0.011). CONCLUSIONS: The
      prevalence of H. pylori infection in Jordanian schoolchildren is high, suggesting
      that most acquisition occurs before the age of 6 years. The seroprevalence for H.
      pylori increases with social deprivation.

PMID- 16412040
TI  - Association of peptic ulcer with increased expression of Lewis antigens, but not
      vacuolating cytotoxin activity or babA2 gene status, in Helicobacter pylori
      strains from China.
AB  - OBJECTIVE: Controversies exist regarding the virulence factors, such as vacA,
      babA2 and Lewis blood group antigens, of Western and Asian strains of
      Helicobacter pylori. The aim of the present study was to determine the
      significance of these potential virulence factors in the Chinese population.
      METHODS: Seventy-two strains of H. pylori isolated from patients in Zhengzhou,
      China, including 43 cases of peptic ulcer (PU) and 29 cases of chronic gastritis,
      were determined. Vacuolating cytotoxin assay was performed by HeLa cells. The
      expression of Le blood group antigens (Le(a), Le(b), Le(x) and Le(y)) was
      performed by enzyme-linked immunosorbent assay (ELISA). babA2 gene was identified
      by polymerase chain reaction. Frequencies were compared using two-tailed Fisher's
      exact test. Cytotoxin activities were compared using Spearman's rank correction
      test. RESULTS: Vacuolating cytotoxin activity was detected in 61 of the 72
      strains (84.7%), but there was no significant difference in vacuolating cytotoxin
      activity (83.7% vs 86.2%, P = 0.821) or titer (4.4 +/- 3.8 vs 4.2 +/- 4.1, P =
      0.876) between the PU and gastritis strains. Significantly more PU strains
      expressed two or more Lewis antigens (Le(x), Le(y), Le(a) or Le(b)) than strains
      from the chronic gastritis patients (90.7% vs 65.5%, P = 0.029). Of the 43
      strains from PU patients, 17 (39.5%) were positive for babA2, compared with 11
      (38.5%) of the 29 strains from gastritis patients (P = 0.924). There was no
      significant difference in the vacuolating cytotoxin activity or titer between
      strains expressing two or more Lewis antigens and less than two antigens (84.5%
      vs 85.7%, P = 1.000; 4.4 +/- 4.2 vs 4.3 +/- 3.2, P = 0.965). Of the 72 H. pylori
      strains, 28 were babA2 positive, of which 24 were cytotoxic, compared with 37 of
      44 babA2-negative strains (P = 1.000). CONCLUSION: The present study suggests
      that PU is associated with increased Lewis antigen expression, but not
      vacuolating cytotoxin production or the presence of babA2, in the H. pylori
      strains in the Chinese population.

PMID- 16412042
TI  - The natural killer T lymphocyte: a player in the complex regulation of autoimmune
      diabetes in non-obese diabetic mice.
AB  - Manipulation of the immune response to specifically prevent autoaggression
      requires an understanding of the complex interactions that occur during the
      pathogenesis of autoimmunity. Much attention has been paid to conventional T
      lymphocytes recognizing peptide antigens presented by classical major
      histocompatibility complex (MHC) class I and II molecules, as key players in the
      destructive autoreactive process. A pivotal role for different types of
      regulatory T lymphocytes in modulating the development of disease is also well
      established. Lately, CD1d-restricted natural killer T (NKT) lymphocytes have been
      the subject of intense investigation because of their ability to regulate a
      diversity of immune responses. The non-classical antigen presenting molecule CD1d
      presents lipids and glycolipids to this highly specialized subset of T
      lymphocytes found in both humans and mice. From experimental models of
      autoimmunity, evidence is accumulating that NKT cells can protect from disease.
      One of the best studied is the murine type 1 diabetes model, the non-obese
      diabetic (NOD) mouse. While the NKT cell population was first recognized to be
      deficient in NOD mice, augmenting NKT cell activity has been shown to suppress
      the development of autoimmune disease in this strain. The mechanism by which CD1d
      restricted T cells exert this function is still described incompletely, but
      investigations in NOD mice are starting to unravel specific effects of NKT cell
      regulation. This review focuses on the role of CD1d-restricted NKT cells in the
      control of autoimmune diabetes.

PMID- 16412043
TI  - The time course of biological and immunochemical allergy states induced by
      anisakis simplex larvae in rats.
AB  - Oral infection by Anisakis simplex third stage larvae (L3) frequently gives rise
      to an allergic response. To comprehend the allergic and immune responses induced
      by L3, we investigated the kinetics of specific antibody isotype expression and
      the time course of biological and immunochemical allergy states using sera
      prepared from rats orally infected with L3 twice, with an interval of 9 weeks
      between infections. Biological and immunochemical allergy states were analysed by
      RBL-2H3 exocytosis and by indirect ELISA for IgE, respectively. The peak IgM at
      reinfection (RI) was comparable or similar to that at primary infection (PI) both
      in levels analysed by indirect ELISA and in antigen recognition analysed by
      Western blot. IgG1 and IgG2a levels were higher and showed accelerated kinetics
      after RI vs. after PI. However, the level of IgG2b was substantially lower than
      that of IgG2a. Peak immunochemical and biological allergy states for RI were
      higher and were reached faster than those for PI. The peak biological allergy
      state was observed at 1 week postreinfection and this occurred sooner than that
      for the peak immunochemical allergy state found at 2 weeks postreinfection. Our
      analysis of the relationship between specific IgE avidity and biological allergy
      state did not show any meaningful correlation. These results suggest that the
      allergic response induced by L3 oral infection is predominantly caused by
      reinfection and that this is accompanied by an elevated IgM level, which further
      suggests that the biological allergy state might not be related to specific IgE
      avidity.

PMID- 16412044
TI  - Phenotype of early cardiomyopathic changes induced by active immunization of rats
      with a synthetic peptide corresponding to the second extracellular loop of the
      human beta-adrenergic receptor.
AB  - In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been
      suggested that the beta1-adrenergic receptor (beta1AR) is a potential pathogenic
      autoantigen. The aim of the present study was to investigate whether immunization
      of rats with a synthetic peptide corresponding to the second extracellular loop
      of the beta1AR (beta1AR EC(II)) was able to induce the early stage of
      cardiomyopathy and also to investigate immunological and receptor functional
      parameters at a transcriptional level to permit insights into the autoimmune
      mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a
      beta1AR EC(II) peptide (H26R) once a month during 12 months and seven control
      rats were injected with vehicle according to the same procedure used for the
      immunized group. Cardiac function, beta1AR autoantibodies and their functional
      effects on cardiomyocytes were analysed. beta1AR receptor signalling,
      immunological and cardiomyocyte stretch markers were determined on
      transcriptional level. In H26R immunized rats, beta1AR autoantibodies were shown
      to be present and functionally active, cardiac functions in terms of fractional
      shortening were decreased and beta1-adrenergic receptor kinase (GRK2) mRNA were
      increased compared with the control group. These data have shown that
      immunization of rats with a putative antigenic peptide was able to induce an
      early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up
      regulation of GRK2 as the first step in the desensitization process of the
      beta1AR, implying the pathological importance of the beta1AR autoantibody.

PMID- 16412045
TI  - Regulation of local and metastatic host-mediated anti-tumour mechanisms by L
      selectin and intercellular adhesion molecule-1.
AB  - Malignant melanoma is often accompanied by a host response of inflammatory cell
      infiltration that is highly regulated by multiple adhesion molecules. To assess
      the role of adhesion molecules, including L-selectin and intercellular adhesion
      molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis
      to the lung of B16 melanoma cells not expressing L-selectin, ICAM-1 or their
      ligands were examined in mice lacking L-selectin, ICAM-1 or both. Primary
      subcutaneous growth of B16 melanoma was augmented by loss of L-selectin, ICAM-1
      or both, while pulmonary metastasis was enhanced by the loss of L-selectin or
      combined loss of L-selectin and ICAM-1. In both situations, the combined loss of
      L-selectin and ICAM-1 exhibited the greatest effect. This enhancement was
      associated generally with a reduced accumulation of natural killer (NK) cells,
      CD4+ T cells and CD8+ T cells and also with a diminished release of interferon
      (IFN)-gamma and tumour necrosis factor (TNF)-alpha but not interleukin (IL)-6.
      Cytotoxicity against melanoma was not defective by the absence of ICAM-1, L
      selectin or both, suggesting that the enhancement of tumour growth and metastasis
      caused by the loss of adhesion molecules results from an impaired migration of
      effector cells into the tissue rather than from a suppression of the cytotoxic
      response. The results indicate that L-selectin and ICAM-1 contribute co
      operatively to the anti-tumour reaction by regulating lymphocyte infiltration to
      the tumour.

PMID- 16412047
TI  - Neo-epitopes are required for immunogenicity of the La/SS-B nuclear antigen in
      the context of late apoptotic cells.
AB  - Mechanisms responsible for the induction of anti-nuclear autoantibodies (ANA)
      following exposure of the immune system to an excess of apoptotic cells are
      incompletely understood. In this study, the immunogenicity of late apoptotic
      cells expressing heterologous or syngeneic forms of La/SS-B was investigated
      following subcutaneous administration to A/J mice, a non-autoimmune strain in
      which the La antigenic system is well understood. Immunization of A/J mice with
      late apoptotic thymocytes taken from mice transgenic (Tg) for the human La (hLa)
      nuclear antigen resulted in the production of IgG ANA specific for human and
      mouse forms of La in the absence of foreign adjuvants. Preparations of
      phenotypically healthy cells expressing heterologous hLa were also immunogenic.
      However, hLa Tg late apoptotic cells accelerated and enhanced the apparent
      heterologous healthy cell-induced anti-La humoral response, while non-Tg late
      apoptotic cells did not. Subcutaneous administration of late apoptotic cells was
      insufficient to break existing tolerance to the hLa antigen in hLa Tg mice or to
      the endogenous mouse La (mLa) antigen in A/J mice immunized with syngeneic
      thymocytes, indicating a requirement for the presence of heterologous epitopes
      for anti-La ANA production. Lymph node dendritic cells (DC) but not B cells
      isolated from non-Tg mice injected with hLa Tg late apoptotic cells presented
      immunodominant T helper cell epitopes of hLa. These studies support a model in
      which the generation of neo-T cell epitopes is required for loss of tolerance to
      nuclear proteins after exposure of the healthy immune system to an excess of
      cells in late stages of apoptosis.

PMID- 16412048
TI  - Oral administration of CpG-ODNs suppresses antigen-induced asthma in mice.
AB  - Oligodeoxynucleotides containing CpG motifs (CpG-ODNs) can protect against
      eosinophilic airway inflammation in asthma. Previously we have found that
      parenteral or mucosal administration of CpG-ODNs is effective in preventing (as
      well as reversing established) disease. In this study, we examined the effect of
      oral CpG-ODNs on the development of immune tolerance. Using an ovalbumin (OVA)
      induced murine model of asthma, we found that CpG-ODNs, administered orally
      around the time of sensitization, prevented eosinophilic airway inflammation in a
      dose-dependent manner. Although oral co-administration of CpG-ODNs with OVA
      (known to induce tolerance) did not significantly change the inhibition of OVA
      induced airway eosinophilia, it did modulate OVA-specific immunoglobulin
      responses: oral administration of OVA alone suppressed OVA-specific IgG1
      production, but only mice that received CpG-ODNs demonstrated enhanced levels of
      OVA-specific IgG2c. Finally, we examined whether oral administration of CpG-ODNs,
      alone or with OVA, could reverse established eosinophilic airway inflammation.
      Again, neither OVA nor CpG-ODNs alone modulated established eosinophilic airway
      inflammation, but a combination of the OVA and CpG-ODNs successfully desensitized
      the mice. This desensitization was associated with suppression of OVA-specific
      IgE and enhancement of OVA-specific IgG2c production. These findings provide the
      first indication that oral administration of CpG-ODNs is effective in preventing
      and reversing antigen-induced eosinophilic airway inflammation. CpG-ODNs may be
      useful as a component of oral immunotherapy to promote tolerance in established
      asthma.

PMID- 16412046
TI  - Involvement of 4-1BB (CD137)-4-1BBligand interaction in the modulation of CD4 T
      cell-mediated inflammatory colitis.
AB  - 4-1BB ligand (4-1BBL) expressed on antigen-presenting cells interacts with 4-1BB
      on activated T cells (especially CD8+ cells) and co-stimulates the latter to
      secrete cytokines and to proliferate. The role of 4-1BB-4-1BBL interaction was
      studied here in a model of colitis based on naive CD4+ T cell transfer to SCID
      mice, a disease model in which CD8 cells do not take part. We found that CD4+ T
      cells from 4-1BB-deficient mice, after transfer in SCID mice, proliferated more
      rapidly compared to wild-type CD4+ T cells. Mice reconstituted with naive CD4+ T
      cells from 4-1BB-deficient mice developed colitis, however, with a mixed Th1/Th2
      response, in contrast to the Th1-type response in mice reconstituted with wild
      type naive CD4+ T cells. Importantly, this altered cytokine response did not
      temper colitis severity. Although it has been reported previously that 4-1BB co
      stimulation may contribute to regulatory T cell functioning, we found that
      CD4+CD25+ regulatory T cells from 4-1BB-deficient mice were perfectly able to
      prevent naive CD4+ T cell-induced colitis. In conclusion, our data provide
      evidence that 4-1BB-4-1BBL interaction modulates the effector CD4+ T cell-driven
      immune response and cytokine production in experimental colitis without affecting
      regulatory T cell function.

PMID- 16412049
TI  - Novel roles of osteopontin and CXC chemokine ligand 7 in the defence against
      mycobacterial infection.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte
      derived macrophage (GM-Mphi) or macrophage CSF (M-CSF)-induced human monocyte
      derived Mphi (M-Mphi) are distinct in terms of the resistance to Mycobacterium
      tuberculosis. To elucidate the role of molecules involved in the functional
      differences between these Mphis, we investigated the gene expression profiles
      using microarray. After culture of CD14+ monocytes with CSFs, Mphis were cultured
      with or without bacillus Calmette-Guerin (BCG) (GM-Mphi-BCG and M-Mphi-BCG). The
      gene expression profiles from these cells were compared. Chemokines highly
      expressed in M-Mphis were selected and evaluated for anti-mycobacterial activity
      and superoxide production. FN1 and FCGR2B were the most up-regulated genes in GM
      Mphi and M-Mphi, respectively. After stimulation with BCG, three chemokine genes
      (Osteopontin (SPP1), CXC chemokine ligand 7 (CXCL7) and CC chemokine ligand 11
      (CCL11)) were highly expressed in M-Mphi-BCG when compared to those in GM-Mphi
      BCG. A significantly increased resistance to M. tuberculosis H37Ra was observed
      after the stimulation of GM-Mphi with SPP1 or CXCL7. Superoxide production levels
      of SPP1- or CXCL7-stimulated GM-Mphis were higher than those of GM-Mphis without
      stimulation. These results indicate that both SPP1 and CXCL7 might have a role in
      the resistance against mycobacteria, at least in part, through augmenting
      reactive oxygen intermediate production in Mphis.

PMID- 16412050
TI  - Increased expression of Toll like receptor 4 on peripheral-blood mononuclear
      cells in patients with coronary arteriosclerosis disease.
AB  - The family of Toll-like receptors (TLRs) initiates innate immune responses, and
      Toll-like receptor 4 (TLR4) was considered to be an important player in the
      initiation and progression of atherosclerotic disease. The aim of the study was
      to investigate the expression of TLR4 on peripheral-blood mononuclear cells
      (PBMCs) in patients with coronary arteriosclerosis disease (CAD). We have
      examined the expression of TLR4 protein and mRNA by flow cytometry (FCM) and real
      time quantitative reverse transcription polymerase chain reaction (RT-PCR). In
      addition, the levels of plasma lipids were determined by automatic biochemistry
      analyzer. The results showed that the positive rates and the mean mRNA copy
      number of TLR4 in CAD group were significantly higher than that in controls. But
      no significant difference was found in the positive rate and the mean mRNA copy
      number of TLR4 between CAD group with normal level of plasma lipids and the CAD
      group with abnormal level of plasma lipids. We suggest that expression level of
      TLR4 on peripheral-blood mononuclear cells is increased in atherosclerotic, but
      the differential expression of TLR4 has no correlation with the level of plasma
      lipids.

PMID- 16412051
TI  - Consumption of erythrocyte CR1 (CD35) is associated with protection against
      systemic lupus erythematosus renal flare.
AB  - Erythrocyte complement receptor type one (E-CR1) is thought to protect against
      immune complex (IC) disease through interactions that lead to E-CR1 consumption,
      and low E-CR1 levels are characteristic of systemic lupus erythematosus (SLE).
      The purpose of this study was to test the hypothesis that E-CR1 consumption can
      predict or mark SLE flare. Recurrently active SLE patients [n = 43; 28 with past
      or present major renal manifestations (SLER) and 15 without (SLENR)], were
      evaluated every 2 months by detailed protocol testing (mean follow-up 22 months),
      including direct measurements of E-CR1 levels using a radioimmunoassay. In all
      patients, detectable E-CR1 levels fluctuated widely through acute periods of
      consumption and regeneration, preventing the use of any single value as a
      baseline. However, when individual chronic baseline values were used, determined
      as the mean of all E-CR1 values 4 months or more from a flare, a clear trend was
      observed. In 16 of 16 instances of non-renal flare in SLER patients, E-CR1 levels
      decreased at flare (mean decrease 34%, P < 0.0001). In contrast, no consistent
      difference was observed for flare in SLENR patients or for renal flare in SLER
      patients. Changes in E-CR1 levels did not correlate with plasma CR1 levels. In
      conclusion, single occurrences of E-CR1 consumption did not generally predict or
      mark SLE flare. However, compared to the average E-CR1 levels measured during no
      flare intervals, E-CR1 consumption in SLER patients at flare was strongly
      associated with freedom from signs of renal involvement. We postulate that E-CR1
      consumption reflects E-CR1 function that includes protecting against SLE
      nephritis.

PMID- 16412052
TI  - Association of apoptosis-related microsatellite polymorphisms on chromosome 1q in
      Taiwanese systemic lupus erythematosus patients.
AB  - Apoptosis is important in the pathogenesis of systemic lupus erythematosus (SLE).
      Several genome-wide scan studies have suggested chromosome 1q as a genetic
      susceptibility locus for SLE. This study investigated the association of
      apoptosis-related genes on chromosome 1q, Fas ligand (FasL), interleukin (IL)-10
      and poly(ADP-ribose) polymerase (PARP), promoter microsatellite multi-allelic
      polymorphisms with SLE susceptibility and clinical characteristics in Taiwan.
      This study recruited 237 SLE patients and 304 healthy controls. FasL, IL-10 and
      PARP promoter microsatellite polymorphisms were genotyped employing gene scan. IL
      10, located on 1q31-32, emerged as a significant susceptibility gene locus in
      Taiwanese SLE (T4 statistic = 0.01). IL-10 CA21 allele was the most common allele
      of 15 identified in Taiwanese, displaying skewed distribution of susceptibility
      in Taiwanese SLE patients. Conversely, the IL-10 CA20 allele showed a protective
      effect of SLE susceptibility. Additionally, the IL-10 CA26 allele displayed a
      negative significant association with ascites and IL-10 CA25 allele increased the
      occurrence of the anti-cardiolipin IgM antibody. This study identified five
      alleles of FasL and nine alleles of PARP of microsatellite polymorphisms in
      Taiwanese patients. FasL and PARP alleles displayed no skewing distribution
      between Taiwanese SLE patients and controls. However, FasL GT15 and PARP CA17
      allele demonstrated a high discoid rash presentation (T4 statistic 0.01 and 0.03,
      respectively) and PARP CA12 allele displayed a significant association with anti
      cardiolipin IgM antibody production (T4 statistic 0.02). IL-10, FasL and PARP
      microsatellite polymorphisms exhibited significant associations with SLE
      susceptibility and/or clinical characteristics in Taiwanese patients. Thus, SLE
      is a complex and multiple genetics determined autoimmune disease. Chromosome 1q23
      42 is an important genetic locus for further SLE subphenotype susceptibility
      study.

PMID- 16412053
TI  - Virological analysis and phenotypic characterization of peripheral blood
      lymphocytes of hepatitis C virus-infected patients with and without mixed
      cryoglobulinaemia.
AB  - In clinical and pathological terms hepatitis C virus (HCV)-infected patients can
      be subdivided into two main groups with and without mixed cryoglobulinaemia (MC).
      Involvement of blood mononuclear cells by HCV has potentially important
      implications. To this end, HCV-RNA levels in peripheral blood lymphocytes (PBL)
      preparations of 20 chronically HCV-infected patients with MC were measured and
      compared with those found in a group of 20 patients without MC matched for age,
      serum HCV-RNA, infectious genotype, source and presumable duration of infection.
      Phenotypic abnormalities of PBL subsets in each group of patients were determined
      by cell surface marker expression and compared. Results showed a significant
      enrichment of HCV-RNA in PBL of MC patients compared with a non-MC group (P =
      0.01). Different distribution of HCV-RNA was accompanied by evidence of an
      increased frequency of circulating B cells. These data indicate that MC patients
      are characterized distinctly by a higher quota of cell-associated viral load.

PMID- 16412054
TI  - Recurrent infections in partial complement factor I deficiency: evaluation of
      three generations of a Brazilian family.
AB  - We report here on the evaluation of a factor I-deficient Brazilian family (three
      generations, 39 members) with strong consanguinity. The complete factor I
      deficient patients (n = 3) presented recurrent respiratory infections, skin
      infections and meningitis; one of them died after sepsis. They presented an
      impaired total haemolytic activity (CH50), low C3, low factor H and undetectable
      C3dg/C3d. Partial factor I deficiency was detected in 16 family members (normal
      low cut-off value was 25 microg/ml). Respiratory infections were the most common
      clinical occurrence among partial factor I-deficient relatives. Two of them were
      submitted to nephrectomy following recurrent urinary tract infections. An
      additional two heterozygous relatives presented with arthritis and rheumatic
      fever. Apparently, patients with partial factor I deficiency are also at higher
      risk for recurrent infections. Vaccination against capsulated bacteria and the
      eventual use of prophylactic antibiotics should be considered individually in
      this patient group.

PMID- 16412055
TI  - Altered naive CD4 and CD8 T cell homeostasis in patients with relapsing-remitting
      multiple sclerosis: thymic versus peripheral (non-thymic) mechanisms.
AB  - We have reported previously that naive T cells from relapsing-remitting multiple
      sclerosis (RRMS) patients have T cell receptor (TCR) repertoire shifts, but the
      basis of these TCR repertoire shifts was uncertain. Here, we questioned whether
      RRMS patients have altered naive CD4 and CD8 T cell homeostasis by studying
      homeostatic proliferation and thymic production in RRMS patients and healthy
      controls. We measured thymic production by quantifying signal joint T cell
      receptor excision circles (sjTRECs). Both naive T subsets from controls showed an
      age-associated decrease in sjTRECs, i.e. evidence of progressive thymic
      involution, but we detected no age-associated decrease in sjTRECs in RRMS
      patients. Instead, naive CD8 T cells from patients had lower sjTRECs (P = 0.012)
      and higher Ki-67 proliferation levels (P = 0.04) than controls. Naive CD4 T cell
      sjTRECs did not differ between patients and controls. However, in RRMS these
      sjTRECs correlated strongly with CD31, a marker expressed by newly generated CD4
      T cells but not by naive CD4 T cells that have undergone homeostatic
      proliferation. HLA-DR2 positivity correlated negatively with naive CD4 T cell
      CD31 expression in RRMS (P = 0.002). We conclude in RRMS that naive T subsets
      have homeostatic abnormalities due probably to peripheral (non-thymic)
      mechanisms. These abnormalities could have relevance for MS pathogenesis, as
      naive T cell changes may precede MS onset.

PMID- 16412056
TI  - Immunomodulation using the recombinant monoclonal human B7-DC cross-linking
      antibody rHIgM12.
AB  - A patient with Waldenstrom's macroglobulinaemia expresses a high titre IgM
      antibody in serum that binds both mouse and human dendritic cells (DC) in a B7-DC
      (PD-L2)-dependent manner. We have reported previously that purified antibody from
      patient serum activates immature and mature DC in vitro, enhancing the ability of
      these professional antigen-presenting cells to activate naive T cells, take up
      antigen, resist a cytokine-depleted environment and secrete immunomodulatory
      cytokines, such as interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha.
      Systemic treatment of experimental animals with this antibody induces potent anti
      melanoma immunity and modulates protectively the recall response against antigen
      challenge through the airway in an experimental model of inflammatory airway
      disease. Here we describe a monoclonal IgM antibody derived from this serum
      immunoglobulin that recapitulates each of these earlier observations, providing
      direct evidence that M protein from the Waldenstrom's patient mediates these
      potent immunomodulatory effects. Furthermore, cell lines expressing this
      recombinant form of the human antibody provide the basis for developing this
      reagent for clinical application.

PMID- 16412057
TI  - Reduced number of interleukin-12 secreting cells in patients with Lyme
      borreliosis previously exposed to Anaplasma phagocytophilum.
AB  - Lyme borreliosis and human granulocytic ehrlichiosis are tick-borne diseases
      caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively.
      Infection with A. phagocytophilum has been observed to induce immunosuppression
      and animal studies suggest that the bacteria might also have prolonged inhibitory
      effects on immune cells. The aim of this study was to investigate the cytokine
      secretion in patients exposed previously to A. phagocytophilum and currently
      infected with B. burgdorferi compared with patients infected with B. burgdorferi
      and seronegative for A. phagocytophilum. Eight patients with erythema migrans and
      antibodies against A. phagocytophilum, 15 patients with erythema migrans and
      negative A. phagocytophilum serology and 15 non-exposed healthy individuals were
      included in the study. Blood mononuclear cells were stimulated with Borrelia
      antigen and the number of cytokine [interleukin (IL)-4, IL-5, IL-12, IL-13 and
      interferon (IFN)-gamma]-secreting cells was detected by enzyme-linked immunospot
      (ELISPOT). This study shows that patients with a previous exposure to A.
      phagocytophilum and a current infection with B. burgdorferi have a lower number
      of Borrelia-specific cells secreting IL-12 compared to Ap seronegative patients
      infected with B. burgdorferi (P < 0.001), indicating impairment in the ability to
      mount strong Th1-responses. We suggest that this mirrors a reduced Th1 response
      caused by A. phagocytophilum which could influence the outcome of the Borrelia
      infection and, speculatively, may also have implications in other conditions.

PMID- 16412058
TI  - Circulating dendritic cells and interferon-alpha production in patients with
      tuberculosis: correlation with clinical outcome and treatment response.
AB  - Dendritic cells (DC) have been characterized recently as having an important role
      in the initiation and control of immunological response to Mycobacterium
      tuberculosis infection. Blood DC have been subdivided into myeloid (mDC) and
      plasmacytoid (pDC) subsets, on the basis of differences in phenotype markers and
      function. Little is known about the enumeration and functional evaluation of
      circulating DC in patients with tuberculosis and their correlation with clinical
      outcome during the course of anti-tuberculous treatment. We assessed circulating
      mDC and pDC counts measured by a newly developed single-platform flow cytometric
      assay based on TruCOUNT, as well as the production of interferon (IFN)-alpha
      after in vitro stimulation by herpes simplex virus (HSV-1) in 24 patients with
      active tuberculosis (TB) and 37 healthy donors. Absolute numbers of both DC
      subsets were decreased significantly in patients with active TB compared to
      controls. Similarly, the production of IFN-alpha was highly impaired. In 13
      patients these parameters were assessed longitudinally, before and after the
      specific anti-microbial treatment. Most interestingly, in all nine patients with
      successful anti-tuberculous therapy there was a significant and marked increase
      of pDC counts and IFN-alpha production. In contrast, no significant longitudinal
      variations in DC counts and IFN-alpha production were observed in four patients
      with lack of response to specific treatment. In conclusion, active TB is
      associated with a defect in blood DC numbers and IFN-alpha production that is
      restored after bacterial clearance and clinical improvement, as a result of
      effective anti-tuberculous treatment.

PMID- 16412059
TI  - In vitro responses of human peripheral blood mononuclear cells to whole-cell,
      particulate and soluble extracts of Leishmania promastigotes.
AB  - Whole-cell and soluble extracts of Leishmania promastigotes have both been used
      as skin test antigens and have also been tested as vaccine candidates. However,
      the differences in antigenicity between soluble and particulate Leishmania
      fractions are not known. We evaluated in vitro responses of PBMC from 30 American
      tegumentary leishmaniasis (ATL) patients and seven noninfected donors to
      different antigen preparations from Leishmania promastigotes, namely Leishmania
      amazonensis and L. braziliensis whole-cell extracts, as well as soluble and
      particulate fractions of L. amazonensis. All Leishmania antigen preparations
      stimulated significantly higher proliferation and interferon (IFN)-gamma
      production (but not interleukin (IL)-10 production) in PBMC from the
      leishmaniasis patients than in cells from the control subjects. The L.
      braziliensis whole-cell extract stimulated significantly higher cell
      proliferation and IFN-gamma production than the L. amazonensis whole-cell extract
      in the group of patients but not in the control group. This result can be
      explained by the fact that the patients were infected with L. braziliensis. Again
      in the group of patients, the PBMC proliferative responses as well as the levels
      of IFN-gamma and IL-10 stimulated by L. amazonensis whole-cell extract were
      significantly greater than those elicited by the L. amazonensis soluble fraction
      but were not significantly different from those elicited by the L. amazonensis
      particulate fraction. We found a higher antigenicity of the particulate fraction
      as compared to the soluble fraction, what suggests that the antigens present in
      the particulate fraction account for most of the antigenicity of whole-cell
      Leishmania promastigote antigen extracts.

PMID- 16412060
TI  - NK cells, displaying early activation, cytotoxicity and adhesion molecules, are
      associated with mild dengue disease.
AB  - During the innate immune response against infections, Natural Killer (NK) cells
      are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated
      after antigenic stimulation in the adaptative response. NK cells increase in
      numbers, after viral infection or vaccination. We investigated the NK cell and
      CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and
      CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The
      majority of NK cells from dengue patients display early markers for activation
      (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the
      acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up
      regulated early in NK cells. Most of these markers appear also on CD8+ T
      lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a
      significant number of patients during early acute infection and its values were
      statistically correlated with NK frequencies and cytotoxic markers on NKs. We
      have therefore shown that dengue virus infection is very likely stimulating a
      cytotoxic response that may be efficient in controlling the virus in synergism
      with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+,
      CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical
      manifestations and might indicate a good prognosis of the disease.

PMID- 16412061
TI  - Glatiramer acetate reduces lymphocyte proliferation and enhances IL-5 and IL-13
      production through modulation of monocyte-derived dendritic cells in multiple
      sclerosis.
AB  - Dendritic cells (DC), as the most effective antigen presenting cells, are
      protagonists of the complex immune network involved in multiple sclerosis (MS)
      lesion formation. Glatiramer acetate (GA), a synthetic random copolymer, is
      thought to exert its therapeutical effect in MS by favouring both Th2 cell
      development and IL-10 production from peripheral lymphocytes as well as by
      systemically affecting the antigen presenting cells. In the present study we
      further analysed the mechanisms of action of GA by using an autologous DC
      lymphocytes (Ly) coculture system from 11 MS patients and 12 matched healthy
      controls (HC). We found that, in MS patients, pretreatment with GA significantly
      decreases the in vitro proliferative effect of DC on lymphocytes as compared to
      HC and to unpulsed or myelin basic protein (MBP)-pulsed DC from MS patients (P <
      0.05). In addition, GA-treated DC from both MS patients and HC significantly
      increase the lymphocyte production of IL-5 and IL-13 as compared to MBP-treated
      DC (P < 0.05). In conclusion our in vitro study may provide new therapeutical
      mechanisms of GA on lymphocytes, antiproliferative and Th2-favouring effects,
      which are mediated by monocyte-derived DC.

PMID- 16412062
TI  - Alveolar macrophage function is altered in patients with lung cancer.
AB  - The alveolar macrophage (AM) is believed to be of central importance in the
      immune response against infection and tumour. We examined patients with lung
      cancer in order to evaluate the immuno-stimulatory potential of AM in lung
      cancer. Bronchoalveolar lavage fluid samples were obtained from patients with
      adenocarcinoma, squamous cell carcinoma, large cell undifferentiated lung
      carcinoma, small cell carcinoma and control subjects. AM were isolated and
      phagocytic function, flow cytometry and cytokine analysis were assessed. AM from
      patients with small and squamous cell carcinoma had impaired uptake in vitro of
      40 nm fluorescent polystyrene beads. AM from patients with small, squamous and
      large cell undifferentiated carcinoma showed impaired uptake of 1000 nm
      fluorescent polystyrene beads. Secreted levels of TNF-alpha and IL-1 from AM of
      patients with small, squamous, and large cell undifferentiated carcinoma were
      decreased compared to controls. Secreted AM IL-6 levels were decreased in small
      and large cell undifferentiated carcinoma. AM from adenocarcinoma patients showed
      similar levels of IL-10, IL-6, IL-1 and TNF-alpha compared to controls.
      Phenotypic analysis demonstrated that patients with small cell carcinoma were the
      only group that showed a decrease in MHC class II surface expression. Surface
      expression of ICAM-1 and CD83 was decreased on AM from patients with large,
      squamous and small cell carcinoma compared to controls but not adenocarcinoma.
      Mannose receptor levels were only decreased on AM from patients with squamous and
      small cell carcinoma but not adenocarcinoma and large cell undifferentiated
      carcinoma. We conclude that there are type-specific alterations in uptake
      ability, cytokine secretion and phenotype of AM from lung cancer patients, which
      may result in an inability to stimulate anti-tumour immunity. The observed
      differences between lung cancer subgroups may explain previously reported
      inconsistencies in descriptions of AM characteristics in lung cancer.

PMID- 16412063
TI  - Age dependency and mutual relations in T and B lymphocyte abnormalities in common
      variable immunodeficiency patients.
AB  - Common variable immunodeficiency (CVID) is primary hypogammaglobulinaemia with an
      unknown aetiopathogenesis. Although various abnormalities of T and B cells have
      been described, their pathogenetic roles are unclear. We determined T and B
      lymphocyte subsets known to be abnormal in CVID in order to disclose possible
      relations between numerical abnormalities in those cells. Markers associated with
      B cell development (CD21, CD27, IgM, IgD) were determined on B lymphocytes
      (CD19+); T lymphocyte development (CD45RA, CD45RO, CD62L) and activation markers
      (CD25, CD27, CD28, CD29, CD38, CD57, HLA-DR) were determined on CD4+ and CD8+ T
      lymphocytes in 42 CVID patients and in 33 healthy controls. Abnormalities in CD4+
      T lymphocyte activation markers (increase in CD29, HLA-DR, CD45RO, decrease in
      CD27, CD62L, CD45RA) were observed particularly in patients with a decreased
      number of memory (CD27+) and mature (CD21+) B cells (group Ia according to the
      Freiburg group's classification), while abnormalities observed in CD8+ cells
      (increase in CD27 and CD28 and decrease in HLA-DR, CD57 and CD38) did not depend
      upon grouping patients together according to B lymphocyte developmental
      subpopulations. We observed correlations between immature B cells (IgM+ CD21-)
      and expression of CD27, CD62L, CD45RA, CD45RO and HLA-DR on CD4+ T cells in CVID
      patients but not in the control group. The expression of CD27 and CD45RA on CD4+
      T lymphocytes, such as the percentage of IgD+ CD27- and IgD+ CD27+ cells in B
      lymphocytes, showed age dependency to be more significant than in the control
      group. Our study demonstrates that T and B lymphocyte abnormalities in CVID are
      partially related to each other. Some of those abnormalities are not definite,
      but may evolve with age of the patient.

PMID- 16412066
TI  - A comparison of segmental vs subtotal/total colectomy for colonic Crohn's
      disease: a meta-analysis.
AB  - OBJECTIVE: Using meta-analytical techniques the present study evaluated
      differences in short-term and long-term outcomes of adult patients with colonic
      Crohn's disease who underwent either colectomy with ileorectal anastomosis (IRA)
      or segmental colectomy (SC). METHODS: Comparative studies published between 1988
      and 2002, of subtotal/total colectomy and ileorectal anastomosis vs segmental
      colectomy, were used. The study end points included were surgical and overall
      recurrence, time to recurrence, postoperative morbidity and incidence of
      permanent stoma. Random and fixed-effect meta-analytical models were used to
      evaluate the study outcomes. Sensitivity analysis, funnel plot and meta
      regressive techniques were carried out to explain the heterogeneity and selection
      bias between the studies. RESULTS: Six studies, consisting of a total of 488
      patients (223 IRA and 265 SC) were included. Analysis of the data suggested that
      there was no significant difference between IRA and SC in recurrence of Crohn's
      disease. Time to recurrence was longer in the IRA group by 4.4 years (95% CI: 3.1
      5.8), P < 0.001. There was no difference between the incidence of postoperative
      complications (OR = 1.4., 95% CI 0.16-12.74) or the need for a permanent stoma
      between the two groups (OR = 2.75, 95% CI 0.78-9.71). Patients with two or more
      colonic segments involved were associated with lower re-operation rate in the IRA
      group, a difference which did not reach statistical significance (P = 0.177).
      CONCLUSIONS: Both procedures were equally effective as treatment options for
      colonic Crohn's disease however, patients in the SC group exhibited recurrence
      earlier than those in the IRA group. The choice of operation is dependent on the
      extent of colonic disease, with a trend towards better outcomes with IRA for two
      or more colonic segments involved. Since no prospective randomised study has been
      undertaken, a clear view about which approach is more suitable for localised
      colonic Crohn's disease cannot be obtained.

PMID- 16412064
TI  - Identification of Leishmania donovani antigens stimulating cellular immune
      responses in exposed immune individuals.
AB  - Human visceral leishmaniasis (VL), also known as kala azar (KA) in India, is a
      systemic progressive disease caused by Leishmania donovani. In VL, Th1 responses
      correlate with recovery from and resistance to disease and resolution of
      infection results in lifelong immunity against the disease. However, recent data
      suggest an important role for interleukin (IL)-10 in maintaining the resistant
      state. We evaluated whole cell extract (WE) and 11 antigenic fractions [F1-F11,
      molecular weight (MW) range of 139-24.2 kDa] from L. donovani (2001 strain, a
      fresh field isolate from Bihar), for their ability to induce in vitro T cell
      proliferation and production of interferon (IFN)-gamma, interleukin (IL)-12, IL
      10 and IL-4 by peripheral blood mononuclear cells (PBMCs) of exposed immune
      individuals (14 patients with history of VL, 10 household endemic contacts) and
      20 non-endemic healthy controls. Twenty-one of 24 exposed individuals and no
      healthy controls showed proliferative response to WE. Whole-extract activated IFN
      gamma, IL-12, IL-10 levels were higher in the exposed group than in controls; IL
      4 was not detectable in any of the samples. Among 21 responders to WE, frequent
      proliferative responses were seen to fractions F1-F4 (MW > 64.2 kDa) and none to
      fractions F5-F11; fractions F1-F11 stimulated comparable levels of IFN-gamma and
      IL-12 while IL-10 levels were higher in response to F5-F11 compared to F1-F4.
      These data demonstrate the presence of immunostimulatory antigens in the high MW
      fractions of whole L. donovani antigen. However, these fractions do not stimulate
      a Th1 response and produce variable amounts of IFN-gamma and the regulatory
      cytokine, IL-10. Hence, these high MW immunostimulatory fractions need to be
      evaluated in greater depth for their possible role as protective antigens.

PMID- 16412067
TI  - Outcome of elective primary surgery for diverticular disease of the sigmoid
      colon: a risk analysis based on the POSSUM scoring system.
AB  - BACKGROUND: The outcome of surgery for diverticular disease of the sigmoid colon
      remains largely unclear. A comparison of studies is hardly possible because risk
      factors for diverticular disease severity and patient-related risk factors are
      lacking. The purpose of this study was to define morbidity and mortality of
      primary surgery for nonacute complications of diverticular disease of the sigmoid
      colon and to identify the risk factors that predict a higher morbidity and
      mortality. METHODS: Patients who underwent elective surgery for complications of
      diverticular disease of the sigmoid colon (n = 149) were identified in a
      prospective computerized morbidity and mortality registration. In all patients,
      the Physiological and Operative Severity Score for the enUmeration of Mortality
      and morbidity (POSSUM) was calculated, as were the morbidity and mortality rates.
      Factors predicting postoperative morbidity and mortality were identified. To
      audit mortality figures, a POSSUM based scoring system is introduced. RESULTS:
      The mortality rate was 4.7% and morbidity rate was 53.7%. Significantly higher
      morbidity rates were correlated with a higher physiological POSSUM score (P =
      0.010). Non-survivors were older (P = 0.029) and also had a higher physiological
      POSSUM score (P < 0.001) and operation severity POSSUM score (P < 0.001).
      CONCLUSION: The morbidity and mortality rates of surgery for nonacute
      complications of diverticular disease of the sigmoid colon are considerable. To a
      large extent, mortality and morbidity are driven by patient- and disease-related
      factors, as expressed by elevated physiological severity and operative severity
      scores and failures of peri-operative management in most deceased patients.

PMID- 16412068
TI  - Consensus conference on the stapled transanal rectal resection (STARR) for
      disordered defaecation.
AB  - An international working party was convened in Rome, Italy on 16-17 June, 2005,
      with the purpose of developing a consensus on the application of the circular
      stapling instrument to the treatment of certain rectal conditions, the so-called
      Stapled Transanal Rectal Resection (STARR). Since the procedure has been
      submitted to only limited objective analysis it was felt prudent to hold a
      meeting of interested individuals for the purpose of evaluating the current
      status and to make conclusions and recommendations concerning the applicability
      of this new approach.

PMID- 16412069
TI  - Self-expanding metallic stents in the treatment of benign colorectal disease:
      indications and outcomes.
AB  - OBJECTIVE: The use of stents for benign colorectal obstruction is considered
      controversial because of a lack of data and perceived high failure and
      complication rates. The aim of this study was to evaluate the indications and
      outcomes following stent placement for benign colorectal disease in a UK district
      general hospital and to review the published literature. PATIENTS AND METHODS:
      Between 1997 and 2004, 11 of 90 attempted stent insertions were performed for
      benign colorectal disease (diverticular disease, 4; anastomotic strictures, 4;
      idiopathic rectal stricture, 1; rectal endometriosis, 1; caecal volvulus, 1).
      Complications and outcomes were analysed from a prospective database. RESULTS:
      Stent insertion was successful in nine patients. Early complications occurred in
      two patients (both with diverticular disease): one patient failed to decompress
      and needed a colostomy and laparotomy was performed in a second patient who
      developed peritonitis after five days although no stent perforation of the bowel
      was identified. Two patients were successfully decompressed and underwent
      subsequent elective surgery with full bowel preparation. Stent placement resulted
      in symptomatic improvement in three out of four patients with anastomotic
      strictures (allowing closure of defunctioning stomas) and in the one patient with
      an idiopathic rectal stricture. Stent migration occurred in two of these patients
      without recurrence of symptoms. Stent fracture occurred in one patient, who
      remained symptomatic. CONCLUSIONS: Self-expanding metallic stents are an
      effective treatment for benign colorectal obstructions, especially anastomotic
      strictures with long-term patency. Stents should be avoided in acute diverticular
      disease because of a higher incidence of complications.

PMID- 16412070
TI  - Mortality after acute surgery for complications of diverticular disease of the
      sigmoid colon is almost exclusively due to patient related factors.
AB  - OBJECTIVE: Auditing the outcome of surgery for complicated diverticulitis of the
      sigmoid colon is difficult. A comparison of studies is hardly possible because
      risk factors both in terms of the severity of diverticulitis and patient-related
      risk factors are neither well described nor standardized. The purpose of this
      study was to define morbidity and mortality of primary surgery for acute
      complications of diverticular disease of the sigmoid colon and to identify the
      relation between risk factors and morbidity and mortality. METHODS: In a
      prospective computerized morbidity and mortality registration from 1990 to 2002,
      114 patients, who underwent surgery on an acute or urgent base for acute
      complications of diverticular disease of the sigmoid colon, were identified. In
      all patients the POSSUM score was calculated. To audit mortality rates a POSSUM
      based scoring system was introduced. RESULTS: Mortality was 16.7%, and morbidity
      71.1%. Higher morbidity rates were significantly related to a higher POSSUM
      physiological score (P = 0.012) and to older age (P < 0.001). Higher mortality
      rates also were significantly related to a higher POSSUM physiological score (P <
      0.001) and older age (P = 0.003). Patients who died had significantly more sepsis
      (P < 0.001), multiple organ failure (P = 0.027), cardiac (P < 0.001) and
      pulmonary (P = 0.013) complications. Gender, operation indication and type of
      neither surgery nor surgeon had a significant relation with morbidity or
      mortality. CONCLUSION: Surgery for acute complications of diverticular disease of
      the sigmoid colon carries a high morbidity rate and a substantial mortality rate.
      The majority of deceased patients had severe comorbidity. Post-operative
      mortality and morbidity are to a large extent driven by patient related factors.
      Elevated physiological severity scores and a lack of peri-operative management
      failures express this in the majority of deceased patients.

PMID- 16412071
TI  - Total subcutaneous fistulectomy combined with Karydakis flap for sacrococcygeal
      pilonidal disease with secondary perianal opening.
AB  - OBJECTIVE: Flap techniques have been performed with success in the treatment of
      pilonidal disease. However, some complex cases such as perianal pilonidal disease
      need special attention. We describe a modification of a well-known flap technique
      for secondary perianal pilonidal disease and its early results. PATIENTS AND
      METHOD: Total subcutaneous fistulotomy combined with Karydakis flap was performed
      on 14 patients. An elliptical incision, described by Karydakis, was made while
      not including the perianal opening. Both sides of the elliptical incision were
      deepened down to the gluteal muscle and postsacral fascia. At the level of
      subcutaneous tissue, attention was directed to the secondary perianal opening. A
      fine probe was inserted through the perianal skin pit, and the connection site
      between the fistula and the cyst was observed. A small circular skin incision was
      made around the probe and the fistula tract was totally excised using
      electrocautery together with the main cyst. The flap was prepared as described by
      Karydakis. Before suturing the flap to the other side, perianal subcutaneous
      tissue was sutured with a fine absorbable material, then, the flap was sutured
      with 4/0 polypropylene. RESULTS: One patient developed seroma. Neither early
      failure in wound healing nor recurrence was observed at a mean of 16.2 months
      (range 4-36 months) follow-up. CONCLUSION: Total subcutaneous fistulectomy plus
      Karydakis flap as a single-stage procedure is an effective surgical modality for
      sacroccocygeal pilonidal disease with secondary perianal opening.

PMID- 16412072
TI  - Salvage abdominoperineal resection after failed Nigro protocol: modest success,
      major morbidity.
AB  - OBJECTIVE: Chemotherapy and radiation (C-XRT) is the first-line therapy for
      epidermoid carcinomas of the anal canal (ECAC). Treatment failure occurs in up to
      33% of patients. Salvage-abdominoperineal resection (APR) is the treatment of
      choice for locoregional failure but pre-operative radiation may increase wound
      complications. The purpose of this study was to evaluate patient survival and
      wound complications after salvage-APR for C-XRT failure. METHODS: We reviewed the
      clinical records of all patients who failed initial C-XRT for ECAC diagnosed
      between 1992 and 2002. We evaluated patient demographics, treatment, tumour
      characteristics, survival and postoperative complications. RESULTS: Nineteen
      patients were identified. The mean age at diagnosis was 55 years. Eight (42%)
      patients had persistent disease; 11 (58%) had tumour recurrence. APR was
      performed in 15 patients. Perineal wound complications occurred in 12 (80%)
      patients; half were major complications. Primary flap reconstruction at time of
      APR was performed in 5 (33%) patients; 2 experienced major wound complications.
      Overall-survival after salvage APR was 40% (6/15) and disease-free survival was
      47% (7/15) at a median follow-up of 14 months (range 2-95 months). Recurrence
      after salvage-APR occurred in 7 (47%) patients at a median follow-up of 5 months
      (range 3-19 months). Kaplan-Meier survival analysis showed an advantage for
      recurrent over persistent disease with 2-year and 5-year survival rates of 75%vs
      34% and 28%vs 0%, respectively. CONCLUSIONS: Failure of C-XRT for ECAC is
      associated with a poor prognosis. Although salvage APR may be curative in some
      patients, perineal wound complications are frequent and primary flap
      reconstruction is not reliable.

PMID- 16412073
TI  - Stapled haemorrhoidopexy in fourth degree haemorrhoidal prolapse: is it
      worthwhile?
AB  - INTRODUCTION: Ten years after the introduction of stapled haemorrhoidopexy few
      studies have stratified patients by degree of haemorrhoidal disease when
      analysing results. Objective The aim of this study was prospectively to evaluate
      116 patients who underwent stapled anopexy conducted by the same surgeon for III
      or IV degree haemorrhoidal prolapse. MATERIALS AND METHODS: One hundred and
      sixteen consecutive patients affected by symptomatic haemorrhoids of III or IV
      degree underwent stapled anopexy using the technique described by Longo in the
      period January 2001 to October 2003. Mean follow-up was 28.1 months. Fischer's
      exact test was used for statistical analysis. Results, in terms of morbidity and
      recurrence rates, were stratified according to degree of haemorrhoidal disease.
      RESULTS: There was no statistically significant difference between the results
      for third degree compared with fourth degree prolapse although there was a trend
      towards increased incidence of postoperative bleeding and recurrence. CONCLUSION:
      Third degree haemorrhoidal prolapse remains the best indication for stapled
      haemorrhoidopexy. This procedure may also be indicated in fourth degree
      haemorrhoidal prolapse. Patients with fourth degree haemorrhoids may be subjected
      to this procedure following adequate discussion of the outcome.

PMID- 16412074
TI  - Reducing surgical outpatient waiting is not the solution to meeting the 2005
      colorectal cancer target.
AB  - OBJECTIVES: The majority of colorectal cancers (CRC) are not diagnosed through
      the Rapid access route (RAR) and follow-ups (FU) may prolong outpatient-waiting
      time for new referrals. The aim of this study was to assess the relative
      contributions of an efficient colorectal clinic and a stringent colonoscopy
      booking system on the total journey time for CRC. PATIENTS AND METHODS: We
      reduced the number of follow-up appointments with the introduction of 'Paper
      clinics'. The composition of the new clinic was determined by the known cancer
      yield through RAR and non-RAR route. A prospective analysis of clinics and CRC
      journey times was undertaken from November 2003 for 13 months, with the new
      outpatient clinic template introduced in December 2003. This coincided with a
      stringent policy on referral pattern for colonoscopy. RESULTS: In our hospital,
      only 4% of RAR yield CRC. Seventy-five percent of our CRC are referred through
      the non-RAR route. Eighty-one percent of follow-ups in a 'paper clinic' were
      discharged. A flexible template for the outpatient clinics, introduced a
      corresponding reduction in follow-up and increased urgent and routine slots.
      There was a progressive drop in the follow-up to new ratio and the waiting times
      for routine and urgent category decreased from a median of 15.9 and 3.4 weeks to
      6.7 and 0.7 weeks, respectively (P < 0.001). Average waiting times for all
      categories fell from 13.35 weeks in November 2003 to 3.5 weeks in December 2004,
      while the number of patients waiting less than 4 weeks rose from 46% to 71%. This
      was associated with reduction in total journey times from 93 days to 62 days (P <
      0.05). DNA rates remained unaffected. CONCLUSION: Modifying outpatient clinic
      composition with 'paper clinics' reduces the waiting time for all referrals to a
      surgical clinic with a modest effect on CRC clinic waiting time. Reduction in the
      total waiting time to first treatment (for CRC) is due to reducing the demand on
      colonoscopy in favour of barium enema. Redirecting the flow of patients towards
      barium enema is perhaps one way of improving the existing CRC journey time to
      first treatment, within existing resources. Achieving the 62 day target for
      cancer journey time will be difficult unless traditional surgical clinic habits
      are challenged.

PMID- 16412075
TI  - Changing trends in the management of colorectal cancers and its impact on cancer
      waiting times.
AB  - OBJECTIVE: The aim of this study was to compare the differences in the
      presentation, management and waiting times for new colorectal cancer (CRC)
      patients over 5 years in a single metropolitan cancer centre. METHODS: A
      retrospective comparative study of new patients with CRC presenting in the years
      1998 and 2003. The groups were compared for referral type, Dukes' stage, site,
      cancer waiting times and primary treatment. RESULTS: There were 72 new patients
      in 1998 and 77 in 2003. In 1998 33% were seen urgently and 28% as emergencies
      whereas in 2003 55% of patients were seen as urgent or target wait patients and
      16% as emergencies. The 2-week target for urgent referrals was met in 50% of
      cases in 1998 and 90% in 2003. In 2003 a higher proportion of patients received
      adjuvant or neoadjuvant treatment. Stage at diagnosis was similar in both groups,
      except stage 'D' which was 21% in 1998 and only 12% in 2003. The 31-day Cancer
      Waiting Time (CWT) target from decision to treat to first treatment would have
      been met in 81% of cases in 1998 and 79% in 2003. The 62-day overall CWT target
      from referral to first treatment for urgent GP referrals would have been met in
      46% of cases in 1998 and 57% in 2003. CONCLUSION: More CRC patients were referred
      urgently in 2003. Most, but not all of these were referred as target waits. The
      time taken for the patient's journey did not improve between the two cohorts,
      possibly in part, because more complex treatments are now provided. Further work
      and perhaps new thinking are needed in order to achieve Cancer Waiting Time
      targets.

PMID- 16412076
TI  - A prospective study of outcome from rubber band ligation of piles.
AB  - OBJECTIVE: With the recent introduction of stapled anopexy it is timely to review
      the benefits of existing treatment options for piles. This study investigates the
      effectiveness and safety of rubber band ligation (RBL) of piles in the outpatient
      setting. PATIENTS AND METHODS: Two hundred and fifty-two consecutive patients
      referred with piles in an 18-month period were studied prospectively. In those
      patients deemed suitable for banding of piles, data were collected on symptoms,
      proctoscopic appearance and degree of piles. Short and long-term outcome data
      were recorded for success of treatment and complications. RESULTS: Of 203
      patients considered suitable and who attended for RBL, 176 kept their follow-up
      appointment. One hundred and forty-eight (84%) had been rendered symptom-free. A
      third of patients, however, had proctoscopic evidence of persistent piles, whilst
      in half of those patients with continuing symptoms the anal cushions appeared
      normal. Six (3%) patients had suffered a complication. Long-term follow-up by
      questionnaire found that 44% of respondents remained asymptomatic at a median of
      46 months from banding. Six (5%) of 117 responders to the questionnaire had,
      though previously normal, suffered a postbanding impairment of continence.
      CONCLUSION: Most patients with piles of any degree can be safely managed by
      rubber band ligation, but return of symptoms in the long term affects more than
      half of patients treated.

PMID- 16412077
TI  - The outcome of surgery in fulminant Clostridium difficile colitis.
AB  - BACKGROUND: The clinical presentation of Clostridium difficile infection ranges
      from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant
      colitis. Although not common, fulminant C. difficile colitis can result in bowel
      perforation and peritonitis with a high mortality rate. Colectomy is often
      indicated in these cases. METHODS: We retrospectively analysed the outcome of 14
      patients who underwent surgery for fulminant C. difficile colitis in the period
      1996-2003 in our Unit. RESULTS: The indications for surgery were systemic
      toxicity and peritonitis (n = 10), radiological and clinical evidence of
      progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation
      with bowel perforation (n = 1). C. difficile infection as the cause of colitis
      was diagnosed pre-operatively in seven (50%) patients, six of whom underwent a
      total colectomy and one a right hemicolectomy. Overall mortality in our series
      was 35.7%. Total colectomy was associated with a lower mortality rate of 11.1%
      (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0.01). One
      patient who underwent a right hemicolectomy (on the basis of deceptively normal
      external appearance of the rest of the colon intra-operatively) survived after a
      prolonged hospital stay. CONCLUSIONS: Early or pre-operative microbiological
      diagnosis of C. difficile infection can be difficult in patients with a fulminant
      presentation. Those patients with C. difficile colitis, who develop signs of
      toxicity, peritonitis or perforation, should undergo a total colectomy as the
      operation of choice.

PMID- 16412079
TI  - Functional analysis of Arabidopsis NCED6 and NCED9 genes indicates that ABA
      synthesized in the endosperm is involved in the induction of seed dormancy.
AB  - The cleavage of 9-cis-epoxycarotenoids to xanthoxin, catalyzed by 9-cis
      epoxycarotenoid dioxygenases, is considered to be the key regulatory step of
      abscisic acid (ABA) biosynthesis. In Arabidopsis, genes for these enzymes form a
      multigene family with nine members, only five of which are thought to be involved
      in ABA production. In contrast to the prominent function of AtNCED3 in stress
      responses, the physiological and developmental role of the other 9-cis
      epoxycarotenoid dioxygenases (NCEDs) remain unknown. Our functional and
      expression analyses have revealed that AtNCED6 and AtNCED9 are required for ABA
      biosynthesis during seed development. Reverse genetic analysis showed that ABA
      levels were reduced in Atnced6 and Atnced9 mutant seeds. In addition, transgenic
      plants overexpressing the AtNCED6 gene overproduced ABA. In accordance with
      mutant phenotypes, both AtNCED6 and AtNCED9 exhibited seed-specific expression.
      Detailed cytological studies were carried out, either by using transcriptional
      fusions of the promoter with GUS and GFP reporter genes, or by in situ
      hybridization. Expression of AtNCED6 was observed exclusively in the endosperm
      during seed development, that of AtNCED9 in both embryo and endosperm at mid
      development. In addition to reduced ABA levels, Atnced6 and Atnced9 mutant seeds
      were also resistant to paclobutrazol, a gibberellin biosynthesis inhibitor.
      Although seeds of single mutants were still dormant, reduced dormancy was
      observed in the Atnced6 Atnced9 double-mutant seeds. These demonstrate that ABA
      synthesized in both the endosperm and the embryo participates in the hormonal
      balance that controls seed dormancy and germination.

PMID- 16412080
TI  - Light-dependent hypersensitive response and resistance signaling against Turnip
      Crinkle Virus in Arabidopsis.
AB  - Resistance to Turnip Crinkle Virus (TCV) in Arabidopsis ecotype Dijon (Di)-17 is
      conferred by the resistance gene HRT and a recessive locus rrt. In Di-17, TCV
      elicits a hypersensitive response (HR), which is accompanied by increased
      expression of pathogenesis-related (PR) genes and high levels of salicylic acid
      (SA). We have previously shown that HRT-mediated resistance to TCV is dependent
      on SA-mediated signal transduction and that increased levels of SA confer
      enhanced resistance to TCV via upregulation of the HRT gene. Here we show that
      HRT-mediated HR and resistance are dependent on light. A dark treatment
      immediately following TCV inoculation suppressed HR, resistance and activation of
      the majority of the TCV-induced genes. However, the absence of light did not
      affect either TCV-induced elevated levels of free SA or the expression of HRT.
      Interestingly, in the dark, transgenic plants overexpressing HRT showed
      susceptibility, but overexpression of HRT coupled with high levels of endogenous
      SA resulted in pronounced resistance. Consistent with these results is the
      finding that exogenous application of SA prior to TCV inoculation partially
      overcame the requirement for light. Light was also required for N gene-mediated
      HR and resistance to Tobacco Mosaic Virus, suggesting that it is an important
      factor which may be generally required during defense signaling.

PMID- 16412081
TI  - Rice plants take up iron as an Fe3+-phytosiderophore and as Fe2+.
AB  - Only graminaceous monocots possess the Strategy II iron (Fe)-uptake system in
      which Fe is absorbed by roots as an Fe3+-phytosiderophore. In spite of being a
      Strategy II plant, however, rice (Oryza sativa) contains the previously
      identified Fe2+ transporter OsIRT1. In this study, we isolated the OsIRT2 gene
      from rice, which is highly homologous to OsIRT1. Real-time PCR analysis revealed
      that OsIRT1 and OsIRT2 are expressed predominantly in roots, and these
      transporters are induced by low-Fe conditions. When expressed in yeast
      (Saccharomyces cerevisiae) cells, OsIRT2 cDNA reversed the growth defects of a
      yeast Fe-uptake mutant. This was similar to the effect of OsIRT1 cDNA. OsIRT1-
      and OsIRT2-green fluorescent protein fusion proteins localized to the plasma
      membrane when transiently expressed in onion (Allium cepa L.) epidermal cells.
      OsIRT1 promoter-GUS analysis revealed that OsIRT1 is expressed in the epidermis
      and exodermis of the elongating zone and in the inner layer of the cortex of the
      mature zone of Fe-deficient roots. OsIRT1 expression was also detected in the
      ccompanion cells. Analysis using the positron-emitting tracer imaging system
      showed that rice plants are able to take up both an Fe3+-phytosiderophore and
      Fe2+. This result indicates that, in addition to absorbing an Fe3+
      phytosiderophore, rice possesses a novel Fe-uptake system that directly absorbs
      the Fe2+, a strategy that is advantageous for growth in submerged conditions.

PMID- 16412082
TI  - Islands of co-expressed neighbouring genes in Arabidopsis thaliana suggest higher
      order chromosome domains.
AB  - Biochemical and cytogenetic experiments have led to the hypothesis that
      eukaryotic chromatin is organized into a series of distinct domains that are
      functionally independent. Two expectations of this hypothesis are: (i) adjacent
      genes are more frequently co-expressed than is expected by chance; and (ii) co
      expressed neighbouring genes are often functionally related. Here we report that
      over 10% of Arabidopsis thaliana genes are within large, co-expressed chromosomal
      regions. Two per cent (497/22,520) of genes are highly co-expressed (r > 0.7),
      about five times the number expected by chance. These genes fall into 226 groups
      distributed across the genome, and each group typically contains two to three
      genes. Among the highly co-expressed groups, 40% (91/226) have genes with high
      amino acid sequence similarity. Nonetheless, duplicate genes alone do not explain
      the observed levels of co-expression. Co-expressed, non-homologous genes are
      transcribed in parallel, share functions, and lie close together more frequently
      than expected. Our results show that the A. thaliana genome contains domains of
      gene expression. Small domains have highly co-expressed genes that often share
      functional and sequence similarity and are probably co-regulated by nearby
      regulatory sequences. Genes within large, significantly correlated groups are
      typically co-regulated at a low level, suggesting the presence of large
      chromosomal domains.

PMID- 16412084
TI  - RABBIT EARS is a second-whorl repressor of AGAMOUS that maintains spatial
      boundaries in Arabidopsis flowers.
AB  - The RABBIT EARS (RBE) gene has been identified as a regulator of petal
      development in Arabidopsis thaliana. We find that second-whorl petals in rbe
      mutants can be replaced with staminoid organs, stamens or filaments and that some
      rbe flowers have increased numbers of sepals and exhibit fusion of sepals. We
      show that these rbe defects are due to AGAMOUS (AG) misexpression in the second
      whorl. Consistent with its role in maintaining the spatial boundary of AG
      expression, rbe enhanced the second-whorl defects present in ap2-1, lug-1 and clf
      2 mutants. In the development of second-whorl organs, RBE acts in the same
      pathway and downstream of UNUSUAL FLORAL ORGANS (UFO). Enhanced first-whorl organ
      fusion in ap2-2 rbe-3, ant-4 rbe-3 and cuc2-1 rbe-3 double mutants supports an
      additional role for RBE in organ separation. RBE thus acts to maintain two
      different types of spatial boundaries in young flowers: boundaries between organ
      primordia within a whorl and boundaries of homeotic gene expression between
      whorls.

PMID- 16412083
TI  - LePLDbeta1 activation and relocalization in suspension-cultured tomato cells
      treated with xylanase.
AB  - Phospholipase D (PLD) has been implicated in various cellular processes including
      membrane degradation, vesicular trafficking and signal transduction. Previously,
      we described a PLD gene family in tomato (Lycopersicon esculentum) and showed
      that expression of one of these genes, LePLDbeta1, was induced by treatment with
      the fungal elicitor xylanase. To further investigate the function of this PLD, a
      gene-specific RNAi construct was used to knock down levels of LePLDbeta1
      transcript in suspension-cultured tomato cells. Silenced cells exhibited a strong
      decrease in xylanase-induced PLD activity and responded to xylanase treatment
      with a disproportionate oxidative burst. Furthermore, LePLDbeta1-silenced cell
      suspension cultures were found to have increased polyphenol oxidase activity, to
      secrete less of the beta-d-xylosidase LeXYL2 and to secrete and express more of
      the xyloglucan-specific endoglucanase inhibitor protein XEGIP. Using an
      LePLDbeta1-green fluorescent protein (GFP) fusion protein for confocal laser
      scanning microscopy-mediated localization studies, untreated cells displayed a
      cytosolic localization, whereas treatment with xylanase induced relocalization to
      punctuate structures within the cytosol. Possible functions for PLDbeta in plant
      pathogen interactions are discussed.

PMID- 16412085
TI  - A universal algorithm for genome-wide in silicio identification of biologically
      significant gene promoter putative cis-regulatory-elements; identification of new
      elements for reactive oxygen species and sucrose signaling in Arabidopsis.
AB  - Short motifs of many cis-regulatory elements (CREs) can be found in the promoters
      of most Arabidopsis genes, and this raises the question of how their presence can
      confer specific regulation. We developed a universal algorithm to test the
      biological significance of CREs by first identifying every Arabidopsis gene with
      a CRE and then statistically correlating the presence or absence of the element
      with the gene expression profile on multiple DNA microarrays. This algorithm was
      successfully verified for previously characterized abscisic acid, ethylene,
      sucrose and drought responsive CREs in Arabidopsis, showing that the presence of
      these elements indeed correlates with treatment-specific gene induction. Later,
      we used standard motif sampling methods to identify 128 putative motifs induced
      by excess light, reactive oxygen species and sucrose. Our algorithm was able to
      filter 20 out of 128 novel CREs which significantly correlated with gene
      induction by either heat, reactive oxygen species and/or sucrose. The position,
      orientation and sequence specificity of CREs was tested in silicio by analyzing
      the expression of genes with naturally occurring sequence variations. In three
      novel CREs the forward orientation correlated with sucrose induction and the
      reverse orientation with sucrose suppression. The functionality of the predicted
      novel CREs was experimentally confirmed using Arabidopsis cell-suspension
      cultures transformed with short promoter fragments or artificial promoters fused
      with the GUS reporter gene. Our genome-wide analysis opens up new possibilities
      for in silicio verification of the biological significance of newly discovered
      CREs, and allows for subsequent selection of such CREs for experimental studies.

PMID- 16412086
TI  - Characterization of a novel putative zinc finger gene MIF1: involvement in
      multiple hormonal regulation of Arabidopsis development.
AB  - Phytohormones play crucial roles in regulating many aspects of plant development.
      Although much has been learned about the effects of individual hormones, cross
      talk between and integration of different hormonal signals are still not well
      understood. We present a study of MINI ZINC FINGER 1 (MIF1), a putative zinc
      finger protein from Arabidopsis, and suggest that it may be involved in
      integrating signals from multiple hormones. MIF1 homologs are highly conserved
      among seed plants, each characterized by a very short sequence containing a
      central putative zinc finger domain. Constitutive overexpression of MIF1 caused
      dramatic developmental defects, including dwarfism, reduced apical dominance,
      extreme longevity, dark-green leaves, altered flower morphology, poor fertility,
      reduced hypocotyl length, spoon-like cotyledons, reduced root growth, and ectopic
      root hairs on hypocotyls and cotyledons. In addition, 35S::MIF1 seedlings
      underwent constitutive photomorphogenesis in the dark, with root growth similar
      to that in the light. Furthermore, 35S::MIF1 seedlings were demonstrated to be
      non-responsive to gibberellin (GA) for cell elongation, hypersensitive to the GA
      synthesis inhibitor paclobutrazol (PAC) and abscisic acid (ABA), and
      hyposensitive to auxin, brassinosteroid and cytokinin, but normally responsive to
      ethylene. The de-etiolation defect could not be rescued by the hormones tested.
      Consistent with these observations, genome-scale expression profiling revealed
      that 35S::MIF1 seedlings exhibited decreased expression of genes involved in GA,
      auxin and brassinosteroid signaling as well as cell elongation/expansion, and
      increased expression of ABA-responsive genes. We propose that MIF1, or the
      protein(s) with which MIF1 interacts, is involved in mediating the control of
      plant development by multiple hormones.

PMID- 16412087
TI  - Functional analysis of EID1, an F-box protein involved in phytochrome A-dependent
      light signal transduction.
AB  - Empfindlicher im Dunkelroten Licht 1 (EID1) is an F-box protein that functions as
      a negative regulator in phytochrome A (phyA)-specific light signalling. F-box
      proteins are components of SCF ubiquitin ligase complexes that target proteins
      for degradation in the proteasome. Here we present further characterization of
      EID1 at the expression level, and show that it regulates photomorphogenesis in
      seedlings, rosette leaf development and flowering. Data on transcript expression
      patterns indicate that EID1 is expressed during all stages of Arabidopsis
      development and exhibits no light response. Microscope studies demonstrate that
      EID1 is localized to the nucleus, where it can form speckles under continuous far
      red light that resemble clastosomes. To characterize the composition and
      formation of SCF(EID1) complexes further, we used two-hybrid and bridge assays in
      yeast and in planta. EID1 interacts specifically with several Arabidopsis Skp1
      like (ASK) proteins and Cullin1 to form stable dimeric and trimeric complexes.
      Our results support a two-step association process in which the F-box protein
      binds first to the ASK adaptor, forming a unit which then associates with the
      catalytic core of the SCF complex. Finally, our data indicate that the EID1
      target interaction domain is composed of two independent modules.

PMID- 16412088
TI  - Genetic dissection of transcriptional regulation by cDNA-AFLP.
AB  - This study demonstrates that cDNA-AFLP is a powerful gel-based genome-scale
      transcript profiling technique to generate quantitative gene expression profiles
      for eQTL mapping. We used cDNA-AFLP to monitor the relative abundance of 912
      transcripts across 50 Arabidopsis thaliana recombinant inbred lines. Estimates
      for heritability of cDNA-AFLP intensity polymorphisms were high, with a median of
      0.30 and an interquartile range of 0.21-0.44. A total of 198 expression
      polymorphisms were significantly linked to specific chromosomal regions (P <
      0.05). Both cis- and trans-acting loci correlated with the variation in gene
      expression levels were found. Some of the trans-acting loci correlated to
      multiple expression polymorphisms, suggesting trans-acting alleles with
      widespread transcriptional effects. Here, we have illustrated that cDNA-AFLP
      constitutes a powerful transcript profiling method that can be utilized for
      'multifactorial genomics' analysis of any plant or animal species for which
      segregating populations and molecular marker maps are available.

PMID- 16412089
TI  - Plastid marker-gene excision by transiently expressed CRE recombinase.
AB  - We report plastid marker-gene excision with a transiently expressed CRE, site
      specific recombinase. This is a novel protocol that enables rapid removal of
      marker genes from the approximately 10,000 plastid genome copies without
      transformation of the plant nucleus. Plastid marker excision was tested in
      tobacco plants transformed with a prototype polycistronic plastid vector,
      pPRV110L, designed to express multiple genes organized in an operon. The pMHB10
      and pMHB11 constructs described here are dicistronic and encode genes for
      herbicide (bar) and spectinomycin (aadA) resistance. In vector pMHB11, expression
      of herbicide resistance is dependent on conversion of an ACG codon to an AUG
      translation initiation codon by mRNA editing, a safety feature that prevents
      translation of the mRNA in prokaryotes and in the plant nucleus. In the vectors,
      the marker gene (aadA) is flanked by 34-bp loxP sites for excision by CRE. Marker
      excision by a transiently expressed CRE involves introduction of CRE in
      transplastomic leaves by agro-infiltration, followed by plant regeneration. In
      tobacco transformed with vectors pMHB10 and pMHB11, Southern analysis and PCR
      identified approximately 10% of the regenerated plants as marker-free.

PMID- 16412090
TI  - Development of a methoxyfenozide-responsive gene switch for applications in
      plants.
AB  - The ecdysone receptor (EcR) has been used to develop gene switches for
      conditional regulation of transgene expression in plants and humans. All EcR
      based gene switches developed to date for use in plants are monopartate and
      require micromolar concentrations of ligand for activation of the transgene; this
      has limited the use of these gene switches. We have developed a Choristoneura
      fumiferana ecdysone receptor (CfEcR)-based two-hybrid gene switch that works
      through the formation of a functional heterodimer between EcR and the retinoid X
      receptor (RXR) upon application of the chemical ligand methoxyfenozide.
      Methoxyfenozide is already registered for field use with an excellent safety
      profile, and it has potential as a gene switch ligand for applications in the
      field. The receptor constructs were prepared by fusing DEF domains (hinge region
      plus ligand-binding domain) of CfEcR to the GAL4 DNA-binding domain and EF
      domains (ligand-binding domain) of ultraspiracle from Choristoneura fumiferana
      (CfUSP) or RXR from Locusta migratoria (LmRXR), Mus musculus (MmRXR) or Homo
      sapiens (HsRXR) to the VP16 activation domain. These receptor constructs were
      tested for their ability to induce expression of the luciferase gene placed under
      the control of 5x GAL4 response elements and -46 35S minimal promoter in tobacco,
      corn and soybean protoplasts and in transgenic Arabidopsis and tobacco plants. By
      adopting the two-hybrid format, the sensitivity of the CfEcR gene switch has been
      improved from micromolar to nanomolar concentrations of methoxyfenozide. The
      sensitivity of the CfEcR + LmRXR two-hybrid switch was 25 to 625 times greater
      than the monopartate gene switch, depending on the plant species tested.

PMID- 16412091
TI  - Increases in alpha4* but not alpha3*/alpha6* nicotinic receptor sites and
      function in the primate striatum following chronic oral nicotine treatment.
AB  - Knowledge of the effects of chronic nicotine is critical considering its
      widespread use in tobacco products and smoking cessation therapies. Although
      nicotine is well known to up-regulate alpha4* nAChR sites and function in the
      cortex, its actions in the striatum are uncertain because of the presence of
      multiple subtypes with potentially opposing effects. We therefore investigated
      the effect of long-term nicotine treatment on nAChR sites and function in the
      primate striatum, which offers the advantage of similar proportions of
      alpha3*/alpha6* and alpha4* nAChRs. Nicotine was given in drinking water, which
      resembles smoking in its intermittent but chronic delivery. Plasma nicotine and
      cotinine levels were similar to smokers. Chronic nicotine treatment (> 6 months)
      enhanced alpha4* nAChR-evoked [(3)H]dopamine release in striatal subregions, with
      an overall pattern of increase throughout the striatum when normalized to uptake.
      This increase correlated with elevated striatal alpha4* nAChRs. Under the same
      conditions, striatal alpha3*/alpha6* nAChR sites and function were decreased or
      unchanged. These divergent actions of chronic nicotine treatment on alpha4*
      versus alpha6* nAChRs, as well as effects on dopamine uptake, allow for a complex
      control of striatal activity to maintain dopaminergic function. Such knowledge is
      important for understanding nicotine dependence and the consequences of nicotine
      administration for the treatment of neurological disorders.

PMID- 16412092
TI  - Different apoptotic mechanisms are activated in male and female brains after
      neonatal hypoxia-ischaemia.
AB  - Sex-related brain injury was evaluated after unilateral hypoxia-ischaemia (HI) in
      C57/BL6 mice on postnatal day (P) 5, 9, 21 or 60, corresponding developmentally
      to premature, term, juvenile and adult human brains. There was no sex difference
      in brain injury when the insult was severe, as evaluated by pathological scoring
      or tissue loss, but when the insult was moderate, adult (P60) females displayed
      less injury. In the immature (P9) male brains, neurones displayed a more
      pronounced translocation of apoptosis-inducing factor (AIF) (loss of AIF from the
      mitochondrial fraction and increase in nuclear AIF) after HI, whereas the female
      brain neurones displayed a stronger activation of caspase 3 (more pronounced loss
      of pro-caspase 3, increase in cleaved caspase 3 and increase in caspase 3
      enzymatic activity). Two other mechanisms of injury, peroxynitrite-induced
      formation of nitrotyrosine and autophagy, were no different between males and
      females at P9. These data show that the CNS is more resistant to HI in adult
      females compared with males, whereas no sex differences were found in the extent
      of injury in neonatal mice. However, critical sex-dependent differences were
      demonstrated in vivo with regard to cellular, apoptosis-related mechanisms.

PMID- 16412093
TI  - Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat
      frontal cortex and hippocampus after damage to the insulin signalling pathway.
AB  - The insulin-resistant brain state is related to late-onset sporadic Alzheimer's
      disease, and alterations in the insulin receptor (IR) and its downstream
      phosphatidylinositol-3 kinase signalling pathway have been found in human brain.
      These findings have not been confirmed in an experimental model related to
      sporadic Alzheimer's disease, for example rats showing a neuronal IR deficit
      subsequent to intracerebroventricular (i.c.v.) treatment with streptozotocin
      (STZ). In this study, western blot analysis performed 1 month after i.c.v.
      injection of STZ showed an increase of 63% in the level of phosphorylated
      glycogen synthase kinase-3alpha/beta (pGSK-3alpha/beta) protein in the rat
      hippocampus, whereas the levels of the unphosphorylated form (GSK-3alpha/beta)
      and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ
      treatment, pGSK-3alpha/beta and Akt/PKB levels tended to decrease (by 8 and 9%
      respectively). The changes were region specific, as a different pattern was found
      in frontal cortex. Structural alterations were also found, characterized by beta
      amyloid peptide-like aggregates in brain capillaries of rats treated with STZ.
      Similar neurochemical changes and cognitive deficits were recorded in rats
      treated with i.c.v. 5-thio-d-glucose, a blocker of glucose transporter (GLUT)2, a
      transporter that is probably involved in brain glucose sensing. The IR signalling
      cascade alteration and its consequences in rats treated with STZ are similar to
      those found in humans with sporadic Alzheimer's disease, and our results suggest
      a role for GLUT2 in Alzheimer's pathophysiology.

PMID- 16412094
TI  - Dynamic regulation of fibroblast growth factor 2 (FGF-2) gene expression in the
      rat brain following single and repeated cocaine administration.
AB  - Administration of drugs of abuse can produce long-lasting effects on brain
      function, which involve modifications at neurotransmitter level as well as
      changes in proteins important for structural alterations of selected brain
      regions. The contribution of trophic factors in these events has so far been
      underestimated. Here, we demonstrate that a single cocaine injection selectively
      up-regulated fibroblast growth factor 2 (FGF-2) mRNA levels in the striatum and
      prefrontal cortex within 2 h, an effect that vanished by 24 h. However, prolonged
      exposure (5 or 14 days) to cocaine treatment produced an enduring elevation of
      FGF-2 mRNA levels that was evident 72 h after the last injection in the
      prefrontal cortex and could even persist for 14 days in the striatum, raising the
      possibility that cocaine treatment primes the brain, resulting in longer-lasting
      FGF-2 up-regulation in regions that are highly innervated by dopaminergic
      projections. The expression of FGF-2 was also significantly increased in the
      midbrain following acute or 5-day injection, suggesting that modulation of FGF-2
      biosynthesis in dopamine-producing cells occurs only during early stages of
      cocaine exposure. Our results point to important mechanistic conclusions as to
      how cocaine alters FGF-2 expression. Whereas cocaine-induced changes in FGF-2
      gene expression following a single injection could be ascribed to increased
      release of transmitters (mainly dopamine), enhanced FGF-2 gene expression
      following repeated administration identifies the trophic factor as part of the
      adaptive changes set in motion by cocaine.

PMID- 16412095
TI  - Identification of amino acid residues important for assembly of GABA receptor
      alpha1 and gamma2 subunits.
AB  - Comparative models of GABA(A) receptors composed of alpha1 beta3 gamma2 subunits
      were generated using the acetylcholine-binding protein (AChBP) as a template and
      were used for predicting putative engineered cross-link sites between the alpha1
      and the gamma2 subunit. The respective amino acid residues were substituted by
      cysteines and disulfide bond formation between subunits was investigated on co
      transfection into human embryonic kidney (HEK) cells. Although disulfide bond
      formation between subunits could not be observed, results indicated that
      mutations studied influenced assembly of GABA(A) receptors. Whereas residue
      alpha1A108 was important for the formation of assembly intermediates with beta3
      and gamma2 subunits consistent with its proposed location at the alpha1(+) side
      of GABA(A) receptors, residues gamma2T125 and gamma2P127 were important for
      assembly with beta3 subunits. Mutation of each of these residues also caused an
      impaired expression of receptors at the cell surface. In contrast, mutated
      residues alpha1F99C, alpha1S106C or gamma2T126C only impaired the formation of
      receptors at the cell surface when co-expressed with subunits in which their
      predicted interaction partner was also mutated. These data are consistent with
      the prediction that the mutated residue pairs are located close to each other.

PMID- 16412096
TI  - Increased levels of cyclins D1 and D3 after inhibition of gap junctional
      communication in astrocytes.
AB  - We showed previously that the inhibition of gap junctional communication in
      astrocytes increased bromodeoxyuridine (BrdU) incorporation and promoted changes
      in the metabolic phenotype destined to fulfil the requirements of cell
      proliferation. In the present study we investigated the changes in the cell cycle
      of astrocytes promoted by the inhibition of intercellular communication through
      gap junctions. Thus, the presence of endothelin-1 and carbenoxolone, two gap
      junction uncouplers, promoted an increase in the percentage of astrocytes found
      in the S, G2 and M phases of the cell cycle, with a concomitant decrease in G0
      and G1 phases. In addition, the levels of Ki-67, a protein present during all
      active phases of the cell cycle but absent from resting cells, increased after
      the inhibition of gap junctional communication. These effects were not observed
      when the inhibition of gap junctions was prevented with tolbutamide, indicating
      that the inhibition of gap junctional communication promotes the entry of
      astrocytes into the cell cycle. The passage of the cells from a quiescent state
      to the cell cycle is ultimately regulated by the degree of retinoblastoma
      phosphorylation. Inhibition of gap junctions increased the phosphorylation of
      retinoblastoma at Ser 780 but not at Ser 795 or Ser 807/811. In addition, the
      levels of cyclins D1 and D3 increased, whereas those of p21 and p27 were not
      significantly modified. Because D-type cyclins are key regulators of
      retinoblastoma protein phosphorylation, it is suggested that the phosphorylation
      of retinoblastoma protein at Ser 780, observed under our experimental conditions,
      is a consequence of the increase in the levels of cyclins D1 and D3. Our work
      provides evidence for the involvement of cyclins D1 and D3 as sensors of the
      inhibition of gap junctional communication in astrocytes.

PMID- 16412097
TI  - Compensation in pre-synaptic dopaminergic function following nigrostriatal damage
      in primates.
AB  - Clinical symptoms of Parkinson's disease only become evident after 70-80%
      reductions in striatal dopamine. To investigate the importance of pre-synaptic
      dopaminergic mechanisms in this compensation, we determined the effect of
      nigrostriatal damage on dopaminergic markers and function in primates. MPTP
      treatment resulted in a graded dopamine loss with moderate to severe declines in
      ventromedial striatum (approximately 60-95%) and the greatest reductions
      (approximately 95-99%) in dorsolateral striatum. A somewhat less severe pattern
      of loss was observed for striatal nicotinic receptor, tyrosine hydroxylase and
      vesicular monoamine transporter expression. Declines in striatal dopamine uptake
      and transporter sites were also less severe than the reduction in dopamine
      levels, with enhanced dopamine turnover in the dorsolateral striatum after
      lesioning. The greatest degree of adaptation occurred for nicotine-evoked
      [(3)H]dopamine release from striatal synaptosomes, which was relatively intact in
      ventromedial striatum after lesioning, despite > 50% declines in dopamine. This
      maintenance of evoked release was not due to compensatory alterations in
      nicotinic receptor characteristics. Rather, there appeared to be a generalized
      preservation of release processes in ventromedial striatum, with K(+)-evoked
      release also near control levels after lesioning. These combined compensatory
      mechanisms help explain the finding that Parkinson's disease symptomatology
      develops only with major losses of striatal dopamine.

PMID- 16412098
TI  - Substrate-mediated enhancement of phosphorylated tyrosine hydroxylase in
      nigrostriatal dopamine neurons: evidence for a role of alpha-synuclein.
AB  - Tyrosine hydroxylase (TH) protein, phosphorylated at serine-40, serine-31 and
      serine-19, and enzyme catalytic activity were compared under basal conditions and
      in activated nigrostriatal dopamine (NSDA) neurons of wild-type and homozygous
      alpha-synuclein knockout mice. Mice were injected with the D2 antagonist
      raclopride to stimulate NSDA neuronal activity in the presence or absence of
      supplemental l-tyrosine. There was no difference in phosphorylated TH levels or
      TH catalytic activity between wild-type and alpha-synuclein knockout mice under
      basal conditions or following raclopride-induced acceleration of NSDA activity.
      In wild-type animals, tyrosine administration potentiated the raclopride-induced
      increase in phosphorylated TH and enzyme activity. However, tyrosine
      administration did not enhance phosphorylated TH levels or enzyme catalytic
      activity in raclopride-stimulated NSDA neurons in alpha-synuclein knockout mice.
      These findings suggest that alpha-synuclein plays a role in the ability of
      tyrosine to either enhance TH phosphorylation or hinder TH inactivation during
      accelerated neuronal activity. The present study supports the hypothesis that
      alpha-synuclein functions as a molecular chaperone protein that regulates the
      phosphorylation state of TH in a substrate and activity-dependent manner.

PMID- 16412099
TI  - Differential regulation of corticotropin releasing factor 1alpha receptor
      endocytosis and trafficking by beta-arrestins and Rab GTPases.
AB  - The corticotropin releasing factor (CRF) type 1alpha receptor, a member of the G
      protein-coupled receptor (GPCR) subfamily B, is involved in the aetiology of
      anxiety and depressive disorders. In the present study, we examined the
      internalization and trafficking of the CRF1alpha receptor in both human embryonic
      kidney (HEK)293 cells and primary cortical neurons. We found that CRF1alpha
      receptor activation leads to the selective recruitment of beta-arrestin2 in both
      HEK293 cells and neurons. We observed distinct distribution patterns of CRF1alpha
      receptor and beta-arrestin2 in HEK293 cells and cortical neurons. In HEK293
      cells, beta-arrestin2-green fluorescent protein (GFP) co-localized with CRF1alpha
      receptor in vesicles at the plasma membrane but was dissociated from the receptor
      in endosomes. In contrast, in primary cortical neurons, beta-arrestin2 and
      CRF1alpha receptor were internalized in distinct endocytic vesicles. By
      bioluminescence resonance energy transfer, we demonstrated that beta-arrestin2
      association with CRF1alpha receptor was increased in cells transfected with G
      protein-coupled receptor kinase (GRK)3 and GRK6 and decreased in cells
      transfected with GRK2 and GRK5. In both HEK293 cells and cortical neurons,
      internalized CRF1alpha receptor transited from Rab5-positive early endosomes to
      Rab4-positive recycling endosomes and was not targeted to lysosomes. However,
      CRF1alpha receptor resensitization was blocked by the overexpression of wild
      type, but not dominant-negative, Rab5 and Rab4 GTPases. Taken together, our
      results suggest that beta-arrestin trafficking differs between HEK293 cells and
      neurons, and that CRF1alpha receptor resensitization is regulated in an atypical
      manner by Rab GTPases.

PMID- 16412100
TI  - Sialylation enhances the secretion of neurotoxic amyloid-beta peptides.
AB  - Alzheimer's disease (AD) is characterized by amyloid-beta peptide (Abeta)
      deposition in the brain. Abeta is produced by sequential cleavage of amyloid
      precursor protein (APP) by beta-secretase (BACE1: beta-site APP-cleaving enzyme
      1) and gamma-secretase. Previously, we demonstrated that BACE1 also cleaves beta
      galactoside alpha2,6-sialyltransferase (ST6Gal-I) and down-regulates its
      transferase activity. Here, we report that overexpression of ST6Gal-I in Neuro2a
      cells enhanced alpha2,6-sialylation of endogenous APP and increased the
      extracellular levels of its metabolites [Abeta by two-fold, soluble APPbeta
      (sAPPbeta) by three-fold and sAPPalpha by 2.5-fold). Sialylation-deficient mutant
      (Lec-2) cells secreted half as much Abeta as wild-type Chinese hamster ovary
      (CHO) cells. Furthermore, wild-type CHO cells showed enhanced secretion of the
      APP metabolites upon ST6Gal-I overexpression, whereas Lec-2 cells did not,
      indicating that the secretion enhancement requires sialylation of cellular
      protein(s). Secretion of metabolites from a mutant APP (APP-Asn467,496Ala) that
      lacked N-glycosylation sites was not enhanced upon ST6Gal-I overexpression,
      suggesting that the N-glycans on APP itself are required for the enhanced
      secretion. In the mouse brain, the amount of alpha2,6-sialylated APP appeared to
      be correlated with the sAPPbeta level. These results suggest that sialylation of
      APP promotes its metabolic turnover and could affect the pathology of AD.

PMID- 16412103
TI  - Patterns of imported malaria at the academic medical center, Amsterdam, the
      Netherlands.
AB  - BACKGROUND: In the Netherlands, cases of imported malaria peaked in the late
      1990s to around 500 (60% Plasmodium falciparum) annually. About 30% to 40% of all
      cases and 57% to 69% of the falciparum cases presented in the Academic Medical
      Center, Amsterdam. In 1991 to 1994, a shift in population groups to more semi
      immune patients, mostly settled immigrants visiting friends and relatives (VFRs),
      was noticed, when compared to 1979 to 1988. This study shows the ongoing trend in
      2000 to 2002. METHODS: All the patients diagnosed with malaria in the Academic
      Medical Center, Amsterdam, during 2000 to 2002 were analyzed. Nonimmune and semi
      immune patients were analyzed separately. RESULTS: A total of 302 patients were
      diagnosed with malaria: 207 (69%) were male; mean age was 34.0 years (range 1-74
      years). Of the 302 patients, 105 (35%) were nonimmune travelers and 197 (65%)
      were considered semi-immune. In 248 (82%) patients, P falciparum was found. In 28
      (9.3%), 15 (5.0%), and 6 (2.0%) cases, Plasmodium vivax, Plasmodium ovale, and
      Plasmodium malariae were diagnosed, respectively. Of the 248 falciparum cases,
      233 (94%) were infected in sub-Saharan Africa; 90% of them had a parasitemia and
      <2 and 4% had a parasitemia exceeding 5% (maximum 43.7%). The majority of the
      falciparum cases (96%) were diagnosed within 30 days after return. The number of
      nonimmune patients with falciparum malaria decreased sharply from 42 in 2000 to
      31 in 2001 to 13 in 2002, accounting for the decrease in all malaria cases, from
      118 in 2000 to 82 in 2002. Fifty-four percent of vivax infections were acquired
      in Southeast Asia and 46% in Latin America and sub-Saharan Africa; 71% of the
      patients presented after 30 days (delayed primary attacks). All the P ovale
      infections were acquired in sub-Saharan Africa (73% delayed primary attacks).
      CONCLUSIONS: During 2000 to 2002, the total number of patients with falciparum
      malaria was steadily decreasing due to a decrease in nonimmune patients. The
      number of semi-immune patients, mostly VFRs and visitors, remained stable. The
      increasing use of more convenient chemoprophylactic drugs, like
      atovaquone/proguanil, appears to improve compliance in those who can afford the
      drug.

PMID- 16412104
TI  - Do travelers really take their mefloquine malaria chemoprophylaxis? Estimation of
      adherence by an electronic pillbox.
AB  - BACKGROUND: Nonadherence to chemoprophylaxis could explain why some travelers get
      malaria. Adherence is notoriously difficult to assess, and most studies have been
      conducted using questionnaires. This study aims at assessing continuous adherence
      more accurately with the help of an electronic pillbox. METHODS: Adult travelers
      to sub-Saharan Africa had to fill a questionnaire on demographic and travel data,
      drug intake, and adverse events. They received oral and written information about
      malaria and mefloquine prophylaxis and a Medication Event Monitoring System
      (MEMS, Aardex, Zug, Switzerland), ie, a bottle closed with a cap containing a
      microprocessor recording date and time of all openings, filled with the exact
      number of mefloquine 250 mg tablets (Lariam, Roche Reinach, Switzerland). The
      MEMS) was returned with the questionnaire after completion of chemoprophylaxis.
      RESULTS: According to the MEMS, only 26 of 81 travelers (32.1%) took all the
      doses at the expected date, another 8 (9.9%) did so but starting late with the
      first dose, and 19 others (23.5%) took all the pills but with intervals of +/-1
      day from the right date. Another eight (9.9%) took all the pills but in a random
      way. The remaining 20 travelers (24.7%) missed some doses, mainly after return.
      Strict adherence as assessed by electronic monitoring was therefore lower than
      adherence measured by questionnaire (32.1% vs 48% in taking all the tablets on
      the right day). There was no difference between the two methods when a broader
      definition of adherence was applied [taking all the tablets on the right day (+/
      1 day); 53/81 (65.4%)], but the MEMS showed that some answers to the
      questionnaire were not reliable. CONCLUSION: The use of electronic pillboxes
      confirms the low adherence of travelers to mefloquine chemoprophylaxis in spite
      of extensive information about the disease and its prevention. Electronic
      assessment of pill taking, for the first time applied to malaria
      chemoprophylaxis, gives new insights into the real adherence of travelers.

PMID- 16412101
TI  - PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42.
AB  - The body of evidence indicating that oligomers of amyloid beta(1-42) (Abeta(1
      42)) produce toxicity to neurons, together with our demonstration that
      prostaglandin H(2) (PGH(2)) oligomerizes amyloid beta(1-42), led to the
      examination of the neurotoxicity of amyloid beta(1-42) treated with PGH(2). The
      neurotoxic effects of Abeta(1-42) incubated with PGH(2) was examined in primary
      cultures of cerebral neurons of mice, monitoring the reduction of 3-(4,5
      dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) as an indicator of
      cell toxicity. Whereas Abeta(1-42) itself, incubated for 24 h, has little or no
      effect on MTT reduction, Abeta(1-42) 24 h after exposure to PGH(2) produced a
      marked inhibition of MTT reduction, comparable with the inhibition resulting from
      Abeta(1-42) that has been oligomerized by incubation for 6 days. Similar results
      were obtained when Abeta(1-42) was incubated with levuglandin E(2) (LGE(2)), a
      reactive aldehyde formed by spontaneous rearrangement of PGH(2). The oligomers
      formed from reaction of Abeta(1-42) with LGE(2) exhibit immunochemical similarity
      with amyloid-derived diffusible ligands (ADDLs), as determined by analysis of the
      products of reaction of Abeta(1-42) with LGE(2) using western blotting with an
      antibody that is selective for ADDLs.

PMID- 16412105
TI  - Impact of imported malaria on the burden of disease in northeastern Venezuela.
AB  - BACKGROUND: Many countries throughout the world are reporting an increasing
      number of imported malaria cases. It is now well documented that population
      movements play an important role in the spread and introduction of malaria
      infection in nonendemic areas. METHODS: We evaluated the contribution of imported
      malaria to the overall malaria burden of disease in an already endemic malaria
      region in Venezuela, where malaria is exclusively caused by Plasmodium vivax. To
      estimate the magnitude of this contribution, we retrospectively analyzed cases of
      imported malaria in Sucre, Venezuela, during a 10-year period (1987-1998).
      RESULTS: During this period, 1,755 (3.8% of the total) cases of imported malaria
      were identified. Most of these cases were imported from the Meridian states into
      Sucre. In Latin America, a major factor in the reemergence and spread of malaria
      is human migration. Surveillance of imported cases of malaria in Venezuela would
      allow us to continue evaluating population migration dynamics and its
      epidemiologic impact on malaria transmission. CONCLUSION: Enhanced surveillance,
      such as the one shown in this study, would help the early identification of
      nonindigenous Plasmodium species and also of resistant Plasmodium strains with a
      potential to spread locally. Population mobility and imported malaria cases may
      add to the magnitude of malaria burden in some regions of Latin America.
      Furthermore, malaria treatment guidelines at local and national levels need to
      incorporate imported malaria cases in their treatment algorithms and into
      chemoprophylactic recommendations for travelers.

PMID- 16412106
TI  - Recommendations for water safety and drowning prevention for travelers.
AB  - Drowning is a serious worldwide, mostly preventable injury problem, particularly
      among international travelers. In 2000, approximately 449,000 people have drowned
      worldwide, and the exact number of travelers is not precisely known. Although
      comprehensive infectious disease information has been available to international
      travelers for many years, advice on injury risk and prevention, more specifically
      on drowning prevention, has received little attention. The goals of this review
      were to develop research-based drowning prevention and water-safety
      recommendations for travelers and to identify research needs for future
      recommendations. A group of injury-prevention and travel-medicine experts
      conducted several rounds of voting and ranking of the strength and evidence of
      drowning-prevention recommendations. Each of the thirty-two recommendations
      created have also been categorized using the Committee to Advise on Tropical
      Medicine and Travel scale and have been framed in the context of preevent, event,
      and postevent categories commonly used in injury-control theory and Haddon's
      Matrix. These recommendations were developed for use by travel-medicine
      professionals or others who prepare individuals for travel. Several of the
      identified interventions to prevent drownings lack conclusive scientific evidence
      of their effectiveness and warrant further studies to better understand their
      true effectiveness. Furthermore, funding for the studies of intervention
      effectiveness and the implications of these interventions for international
      travelers are essential, yet insufficient.

PMID- 16412107
TI  - Drugs and drug administration in extreme environments.
AB  - Emergency medicine must often cope with harsh climates far below freezing point
      or high temperatures, and sometimes, an alternative to the normal route of drug
      administration is necessary. Most of this information is not yet published.
      Therefore, we summarized the information about these topics for most drugs used
      in medical emergencies by combining literature research with extensive personal
      communications with the heads of the drug safety departments of the companies
      producing these drugs. Most drugs can be used after temperature stress of limited
      duration. Nevertheless, we recommend replacing them at least once per year or
      after extreme heat. Knowledge about drugs used in extreme environments will be of
      increasing importance for medical personnel because in an increasingly mobile
      society, more and more people, and especially elderly -often with individual
      medical risks-travel to extreme regions such as tropical or arctic regions or to
      high altitude, and some of them need medical care during these activities.
      Because of this increasing need to use drugs in harsh climates (tourism,
      expeditions, peace corps, military, etc) the actual International Congress of
      Harmonization recommendations should be added with stability tests at +50 degrees
      C, freezing and oscillating temperatures, and UV exposure to simulate the storage
      of the drugs at "outdoor conditions."

PMID- 16412108
TI  - The US-Certified Yellow Fever Vaccination Center Registry: a tool for travelers,
      state health departments, and vaccine providers.

PMID- 16412109
TI  - Onchocerciasis-associated limb swelling in a traveler returning from Cameroon.
AB  - Travelers to West Central Africa are at risk for infection with Onchocerca
      volvulus. We describe the case of an adventurous traveler who became infected
      with O volvulus after a 10-day stay in rural Cameroon. Two years after his
      return, he was diagnosed with a 3-month history of limb swelling with pruritus
      and fixed edema of the right arm. He was successfully treated by a single dose of
      ivermectin, with an additional treatment with doxycycline. The patient was
      followed-up during 1 year after therapy without relapse. Such travelers
      experiencing unusual dermatitis syndromes should prompt evaluation for
      onchocerciasis.

PMID- 16412110
TI  - Reiter's syndrome (reactive arthritis) and travelers' diarrhea.
AB  - Reiter's syndrome [also called reactive arthritis (ReA)] is the triad of
      arthritis, urethritis, and conjunctivitis. Two cases of Reiter's syndrome
      triggered by travelers' diarrhea are presented. Health care providers should
      suspect ReA in travelers with joint symptoms and antecedent diarrheal disease.

PMID- 16412111
TI  - Leprosy in a backpacker.

PMID- 16412115
TI  - A systematic review and meta-analysis of the efficacy and safety of cyclosporin
      for the treatment of atopic dermatitis in dogs.
AB  - The efficacy of cyclosporin A (CsA) for the treatment of canine atopic dermatitis
      was evaluated based on the systematic review of prospective clinical trials
      published between 2001 and 2005. Ten studies with adequate design characteristics
      were included. These studies enrolled 799 dogs, 672 (84%) treated with CsA, 160
      (20%) with placebo, 74 (9%) with oral glucocorticoids and 23 (3%) with
      antihistamines. Treatment duration varied from 2 weeks to 6 months. For safety
      analysis, data were available from 660 dogs. Lesion scores were improved from
      baseline in the range of 30-52%, 53-84% and 52-69% after 4, 6 and 16 weeks,
      respectively. The percentage of dogs with only mild pruritus rose from 0-13% at
      inclusion to 32-59% and 46-90% after 4 and 12 weeks, respectively. In most
      studies, the frequency of CsA administration could be reduced to every other day
      in 40% to 50% of patients after 4 weeks and to twice weekly in 20-26% of the dogs
      after 12-16 weeks. Meta-analysis confirmed highly significant effects of CsA
      compared to placebo, but none between oral CsA and glucocorticoids. The initial
      disease severity, age or body weight of subjects did not influence treatment
      success. Improvement by more than 50% over baseline of lesion scores was
      predictive of a better response during treatment maintenance. Vomiting and soft
      stools/diarrhoea were the most frequent adverse events seen at least once during
      the studies. These occurred in 25% and 15% of subjects, respectively. The
      frequency of each other type of adverse events was lower than 2.1%. In summary,
      the administration of CsA for the treatment of canine AD was found to be as
      effective as that of glucocorticoids, and adverse effects were minimal.

PMID- 16412116
TI  - Immunolocalization of aquaporin-5 expression in sweat gland cells from normal and
      anhidrotic horses.
AB  - Western blot analysis showed that sweat gland cells from freely sweating horses
      expressed the water channel aquaporin-5 (AQP-5). Immunohistochemistry revealed a
      strong AQP-5-like activity reaction at the apical membrane of the glandular
      secretory cells, which was absent from the surrounding myoepithelium and all
      other skin structures. In anhidrotic horses, AQP-5 was also found at the apical
      membrane of the luminal sweat gland cells, but the level of expression reduced
      with the length of time that the animal had displayed anhidrosis. The level of
      AQP-5 expression was substantially reduced in animals with long-term anhidrosis,
      hence implicating water channel impairment as a possible factor in the
      development of this disorder.

PMID- 16412117
TI  - Pilot investigation of a model for canine atopic dermatitis: environmental house
      dust mite challenge of high-IgE-producing beagles, mite hypersensitive dogs with
      atopic dermatitis and normal dogs.
AB  - Although canine atopic dermatitis (cAD) is common, few models are available. The
      aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to
      house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were
      environmentally challenged with HDM using various doses and protocols. Similar
      challenge protocols were used in positive and negative control dogs: three dogs
      with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and
      three normal dogs without history of skin disease and negative IDT to HDM. All
      high-IgE beagles and all atopic dogs developed severe cutaneous lesions and
      pruritus after challenge. Lesions were erythematous papules and macules in
      contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They
      were first visible after 6 h and increased in severity over time. No normal dog
      developed pruritus or lesions. Biopsies of representative lesions in the high-IgE
      beagles were taken for histopathology and immunohistochemistry. There was
      superficial perivascular dermatitis with mononuclear infiltrates and spongiosis.
      Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with
      hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that
      this colony of high-IgE beagles develops a dermatitis that clinically,
      histopathologically and immunologically resembles the naturally occurring canine
      disease. It is also concluded that this modality of challenge is not irritating
      to normal dogs but induces flare-ups in hypersensitive atopic dogs.

PMID- 16412118
TI  - Mouse epidermal development: effects of retinoic acid exposure in utero.
AB  - Epidermal morphogenesis was studied in vivo following prenatal exposure to
      retinoic acid (RA). In pregnant mice, a single oral dose of RA on day 11.5 of
      gestation failed to induce histological changes in fetal epidermal development
      except in epidermal thickness. Epidermal thickness increased from 16.5 days post
      coitum (dpc) onwards, and temporal and spatial epidermal modifications in
      keratins K5 and K14 related to proliferative activity of keratinocytes were
      observed. An RA effect on cell proliferation was supported by a statistically
      significant increase in the number of epidermal S-phase cells, containing BrdU
      incorporated DNA in RA-exposed mice compared with nonexposed animals. The
      prolonged in utero action of RA on epidermal proliferative activity in fetuses
      and newborns suggests a long-term RA effect that may play a role on the
      development and evolution of diseases in adult skin.

PMID- 16412119
TI  - The impact of body site, topical melatonin and brushing on hair regrowth after
      clipping normal Siberian Husky dogs.
AB  - The aims of this study were to determine the impact of body site, vigorous
      brushing and topical melatonin treatment on hair regrowth after clipping normal
      dogs. Siberian Husky dogs were randomly assigned to three groups of eight dogs
      each. All dogs had the lumbosacral region and both lateral thighs clipped. The
      left thigh and lumbosacral area received no treatment and were compared in all 24
      dogs. Eight dogs had the right thigh treated with 0.1% melatonin twice daily for
      2 months, and hair regrowth was compared with the left thigh. Eight dogs had the
      right thigh brushed twice daily for 2 months, and hair regrowth was compared with
      the left thigh. Eight dogs had neither thigh treated. Hairs were plucked before
      and 2 months postclipping, and the proportion of hair growth from the original
      length was calculated and compared as described above. Biopsy samples were
      collected before and after treatment to determine if brushing induced dermal
      inflammation and melatonin increased the proportion of anagen follicles.
      Proportionally, left thigh hairs were significantly longer compared to
      lumbosacral hairs 2 months postclipping. No significant differences in hair
      regrowth were noted between the nontreated thigh and the thigh treated with
      melatonin or brushed. No significant difference in dermal inflammation was noted
      before and after brushing. No significant differences were observed in the
      proportion of anagen follicles before and after topical melatonin treatment. Our
      results showed that the hairs in the lumbosacral region were proportionally
      shorter than lateral thigh hairs 2 months postclipping. Moreover, topical
      melatonin and brushing had no impact on hair regrowth after clipping normal dogs.

PMID- 16412120
TI  - A retrospective study of cutaneous equine sarcoidosis and its potential
      infectious aetiological agents.
AB  - Nine horses from ages 5 to 21 years were diagnosed with cutaneous equine
      sarcoidosis (ES) over an 18-year period. In addition to skin, the lungs were
      frequently involved, with other organ systems affected less commonly. A
      predisposition for thoroughbreds and geldings was noted. Cutaneous lesions and
      signs included crusts, scales, alopecia and pruritus. These were found at various
      sites, particularly the legs/thighs/elbows, thorax, neck, face and ventral
      abdomen. Three horses were euthanized shortly after hospitalization; others
      survived as long as 12 years. Histopathologic stains, immunohistochemistry and
      polymerase chain reaction assays on paraffin-embedded cutaneous specimens from
      eight horses for Mycobacterium spp., Coccidioides immitis, Cryptococcus
      neoformans, Corynebacterium pseudotuberculosis, and Borrelia burgdorferi were all
      negative. The aetiology of ES is unlikely microbial and continues to be a
      diagnosis of exclusion. ES, when limited to the skin, is associated with a good
      prognosis, with either partial or complete response to glucocorticoid therapy in
      all the surviving horses.

PMID- 16412121
TI  - Generalized alopecic and cystic dermatosis in a cat: a counterpart to the
      hairless mouse phenotype or a unique congenital dermatosis?
AB  - A 2-year-old, male neutered, domestic semi-long-haired cat was presented with a
      1.5-year history of progressive, initially nonpruritic alopecia and malodorous
      greasy exudate affecting the distal extremities, trunk and neck but sparing the
      head and tail. The extensive alopecia and 'seborrhoea' were associated with
      severe thickening of the skin and fold formation on the dorsal head and distal
      extremities as well as the lateral thorax and abdomen. The hair was easily
      epilated, numerous milia were seen on the ventral abdomen and the caudal and
      lateral thighs, and mild paronychia was present. Histopathological examination of
      skin biopsies revealed marked cystic dilation of hair follicles and sebaceous
      glands with follicular hypoplasia, infundibular hyperkeratosis and variable
      associated inflammation. Systemic glucocorticoid therapy in combination with
      topical washes with chlorhexidine and miconazole resulted in a marked improvement
      and some hair regrowth, but the cat was subsequently lost to follow-up. The
      dermatosis resembles a number of conditions in other species, but it is not clear
      whether it is a counterpart to the hairless mutant mouse or is a unique
      dermatosis.

PMID- 16412122
TI  - Immediate hypersensitivity to leaf extracts of Callisia fragrans (inch plant) in
      a dog.
AB  - Contact with members of the plant family Commelinaceae, which includes wandering
      jew (Commelina spp. formerly called Tradescantia spp.) and inch plant (Callisia
      fragrans), can cause cell-mediated contact dermatitis in dogs. However, reports
      of canine IgE-mediated hypersensitivity to these plants have not been published.
      The purpose of this study was to discover whether IgE antibodies specific for
      extractable components of C. fragrans could be identified in serum from a dog
      that had anaphylactic shock after exposure to the plant and after skin patch
      testing with the sap from a leaf of C. fragrans. Separate aqueous extracts of
      leaves and flowers of C. fragrans were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Serum from a
      dog with no history or symptoms of any allergies showed no specific IgE
      antibodies against the leaf extract. Serum from a dog with clinical symptoms of
      delayed, but not immediate hypersensitivity to leaf sap from C. fragrans, showed
      only minor IgE recognition of a single 65 k component in sap extracted from
      leaves harvested in summer but not in winter. However, IgE antibodies to a serum
      dilution of 1:200 specific for several components of the leaf extract were seen
      in serum from the dog that had anaphylactic shock after exposure to sap. The
      molecular weights of these molecules were in the range 51 k to 83 k. The bands on
      the immunoblots did not match with prominently stained protein bands in the gel,
      but instead identified molecules in a lightly stained area of the gel with
      diffuse bands. Testing for glycans indicated that the carbohydrate side chains of
      glycoproteins contributed significantly to the immunoreactivity of the putative
      allergens. All three dog sera failed to show any immunoreactivity against the
      extract from the flowers of C. fragrans.

PMID- 16412123
TI  - Dermatitis in a dog induced by Straelensia cynotis: a case report and review of
      the literature.
AB  - This case report describes a highly pruritic, papular and crusted dermatitis
      affecting the dorsum of a dog and microscopically diagnosed as dermatitis induced
      by Straelensia cynotis. Histologically, each papule was characterized by a
      dilated hair follicle with marked pseudoepitheliomatous hyperplasia,
      perifollicular mucinosis and an abundant mononuclear infiltration by plasma and
      mast cells. Each dilated follicle contained a larval mite. A therapy including
      systemic ivermectins and oral antibiotic therapy was initiated, but the clinical
      response was poor. To the best of the authors' knowledge, this is the first
      report of straelensiosis in Portugal, and the second in Europe.

PMID- 16412124
TI  - Three cases of immune-mediated adnexal skin disease treated with cyclosporin.
AB  - Cyclosporin is currently considered a new and interesting drug in veterinary
      dermatology for the treatment of immune-mediated skin diseases, and a safe and
      effective alternative to immunosuppressive therapy with glucocorticoids. The
      authors report a case of granulomatous folliculitis and furunculosis and of
      sebaceous adenitis in two cats and a case of alopecia areata in a dog,
      successfully controlled with cyclosporin.

PMID- 16412126
TI  - The effect of the duration of propofol administration on recovery from anesthesia
      in cats.
AB  - OBJECTIVE: To determine the effect of induction, a 30-minute, and a 150-minute
      infusion of propofol on the rate of recovery in cats. STUDY DESIGN: Randomized,
      cross-over, prospective experimental study. ANIMALS: Six healthy adult spayed
      female cats (mean 4.3, range 2-7 years old) weighing 3.9 +/- 0.5 kg. METHODS:
      Cats received each of three treatments: anesthetic induction with propofol (T1),
      induction followed by a 30-minute infusion (T30) and induction followed by a 150
      minute infusion (T150). Propofol infusions were increased or decreased to
      maintain a sluggish pedal withdrawal reflex. Animals were monitored throughout
      the anesthetic period and during the recovery. Venous blood samples were
      collected from a central venous catheter before anesthesia and at 30 minutes for
      the 30-minute infusion and at 30, 60, 90, 120 and 150 minutes for the 150-minute
      infusion. The ability of the cat to lift its head, crawl, stand and walk without
      ataxia was recorded at 5, 10, 20, 40, 60, 80, 120, 160, 180, 210 and 240 minutes
      after the completion of propofol administration. Data from physiological values
      were analyzed using either a Student's t-test (30-minute infusion) or an anova
      (150-minute infusion). A nonparametric Friedman test (and post-hoc Tukey's
      Studentized range test) was used to determine whether there were differences in
      the time taken to recover. Results were considered significant if p < 0.05.
      RESULTS: Time taken to walk without ataxia was significantly greater in T150 (148
      +/- 40 minutes) compared with T1 (80 +/- 15 minutes) and T30 (74 +/- 26 minutes).
      (No other recovery times were significantly different). Anesthesia with propofol
      was accompanied by a moderate but significant respiratory depression and a
      decrease in PCV and total protein. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged
      anesthesia with propofol in healthy cats may be associated with a delayed
      recovery.

PMID- 16412127
TI  - Comparison of two pre-anaesthetic medetomidine doses in isoflurane anaesthetized
      sheep.
AB  - OBJECTIVE: To compare the sedative, anaesthetic-sparing and arterial blood-gas
      effects of two medetomidine (MED) doses used as pre-anaesthetic medication in
      sheep undergoing experimental orthopaedic surgery. STUDY DESIGN: Randomized,
      prospective, controlled experimental trial. ANIMALS: Twenty-four adult, non
      pregnant, female sheep of various breeds, weighing 53.9 +/- 7.3 kg (mean +/- SD).
      METHODS: All animals underwent experimental tibial osteotomy. Group 0 (n = 8)
      received 0.9% NaCl, group L (low dose) (n = 8) received 5 microg kg(-1) MED and
      group H (high dose) (n = 8) received 10 microg kg(-1) MED by intramuscular (IM)
      injection 30 minutes before induction of anaesthesia with intravenous (IV)
      propofol 1% and maintenance with isoflurane delivered in oxygen. The propofol
      doses required for induction and endtidal isoflurane concentrations (F(E')ISO)
      required to maintain anaesthesia were recorded. Heart and respiratory rates and
      rectal temperature were determined before and 30 minutes after administration of
      the test substance. The degree of sedation before induction of anaesthesia was
      assessed using a numerical rating scale. Arterial blood pressure, heart rate,
      respiratory rate, FE'ISO, end-tidal CO2 (FE'CO2) and inspired O2 (FIO2)
      concentration were recorded every 10 minutes during anaesthesia. Arterial blood
      gas values were determined 10 minutes after induction of anaesthesia and every 30
      minutes thereafter. Changes over time and differences between groups were
      examined by analysis of variance (anova) for repeated measures followed by
      Bonferroni-adjusted t-tests for effects over time. RESULTS: Both MED doses
      produced mild sedation. The dose of propofol for induction of anaesthesia
      decreased in a dose-dependent manner: mean (+/-SE) values for group 0 were 4.7
      (+/-0.4) mg kg(-1), for group L, 3.2 (+/-0.4) mg kg(-1) and for group H, 2.3 (+/
      0.3) mg kg(-1)). The mean (+/-SE) FE'ISO required to maintain anaesthesia was 30%
      lower in both MED groups [group L: 0.96 (+/-0.07) %; group H: 1.06 (+/-0.09) %]
      compared with control group values [(1.54 +/- 0.17) %]. Heart rates were
      constantly higher in the control group with a tendency towards lower arterial
      blood pressures when compared with the MED groups. Respiratory rates and PaCO2
      were similar in all groups while PaO2 increased during anaesthesia with no
      significant difference between groups. In group H, one animal developed a
      transient hypoxaemia: PaO2 was 7.4 kPa (55.7 mmHg) 40 minutes after induction of
      anaesthesia. Arterial pH values and bicarbonate concentrations were higher in the
      MED groups at all time points. CONCLUSION AND CLINICAL RELEVANCE: Intramuscular
      MED doses of 5 and 10 microg kg(-1) reduced the propofol and isoflurane
      requirements for induction and maintenance of anaesthesia respectively.
      Cardiovascular variables and blood gas measurements remained stable over the
      course of anaesthesia but hypoxaemia developed in one of 16 sheep receiving MED.

PMID- 16412128
TI  - cis-Atracurium in dogs with and without porto-systemic shunts.
AB  - OBJECTIVE: To evaluate the non-depolarizing neuromuscular blocking drug cis
      atracurium in dogs with porto-systemic shunts, and to compare it in clinically
      normal animals. ANIMALS: Thirteen dogs of mixed breed and sex, aged between 3 and
      31 months old, weighing 2.2-25.5 kg, with ASA physical status II-IV, and
      undergoing surgical attenuation of porto-systemic shunt. A control group of 11
      bitches of mixed breed, between 8 and 60 months old, and weighing 4.5-41.0 kg,
      all ASA physical status I, undergoing routine ovarohysterectomy were also
      studied. MATERIALS AND METHODS: Pre-anaesthetic medication was an opioid
      analgesic, given either alone or in combination with acepromazine. Following
      induction of general anaesthesia with intravenous (IV) propofol and oro-tracheal
      intubation, anaesthesia was maintained using isoflurane in either oxygen or
      oxygen and nitrous oxide. Ventilation was controlled. The train of four (TOF)
      technique was used to monitor neuromuscular blockade. An initial dose of 0.1 mg
      kg(-1)cis-atracurium was given IV and additional doses of 0.03 mg kg(-1)cis
      atracurium were administered when at least one twitch of the TOF was present.
      RESULTS: Except for one dog that was killed during surgery because its anomaly
      was inoperable, all animals recovered satisfactorily from anaesthesia and
      surgery. In dogs with porto-systemic shunt, onset of neuromuscular blockade was
      3.1 +/- 1.1 minutes (mean +/- SD) and in control dogs was 3.4 +/- 0.7 minutes
      (not significantly different). Neuromuscular blockade lasted 34 +/- 13 minutes in
      dogs with porto-systemic shunt and 29 +/- 17 minutes in control dogs (not
      significantly different). CONCLUSIONS: The presence of porto-systemic shunt did
      not affect the rate of onset or duration of action of cis-atracurium. CLINICAL
      RELEVANCE: cis-Atracurium may have a use in veterinary anaesthesia for producing
      neuromuscular blockade in dogs with hepatic insufficiency, including those with
      porto-systemic shunt.

PMID- 16412129
TI  - Comparison of airway size with some phenotypic parameters in Dalmatian puppies: a
      practical method to estimate endotracheal tube size.
AB  - OBJECTIVE: To determine the relationship between 16 phenotypic parameters and the
      diameter of the tracheal lumen and endotracheal tube size (ETS) in Dalmatian
      puppies. STUDY DESIGN: A prospective nonblinded study. ANIMALS: Twenty-nine
      Dalmatian puppies, <5 months of age, referred to the Veterinary Faculty Clinics,
      Burdur, Turkey. MATERIALS AND METHODS: The diameter of the tracheal lumen was
      assessed using lateral cervical radiographs and the ETS was determined for each
      puppy. The relationships between ETS and body mass, age, dimensions of carpal and
      digital pads of the thoracic limb, length of the philtrum and the distance
      between the philtrum and lateral nasal edges were analysed statistically.
      RESULTS: The linear relationships between the ETS and the vertical length of the
      fourth digital pad (r2 = 0.915), and body mass (r2 = 0.908) were higher than with
      other parameters. Two predictive formulae for ETS derived from regression lines
      are: ETS +/- SE (0.20) = [body mass (kg) x 6/10]+2.5 and ETS +/- SE (0.19) =
      [vertical length of fourth digital pad (cm) x 6] - 2. CONCLUSIONS AND CLINICAL
      RELEVANCE: These formulae provide a practical guide to ETS selection in Dalmatian
      puppies.

PMID- 16412130
TI  - Evaluation of histamine release during constant rate infusion of morphine in
      dogs.
AB  - OBJECTIVE: To evaluate histamine release and selected physiologic variables
      during constant rate infusion (CRI) of morphine in dogs. ANIMALS: Five healthy,
      conscious, intact female dogs. MATERIAL AND METHODS: Using a Latin square,
      repeated-measures design, dogs were randomly assigned to three treatment groups
      to receive a 4-hour CRI of saline (SAL), or a loading dose of morphine at 0.3 mg
      kg(-1) (LM), or 0.6 mg kg(-1) (HM), followed by an infusion of 0.17 mg kg(-1)
      hour(-1) (LM) and 0.34 mg kg(-1) hour(-1) (HM) respectively. Dogs received each
      of the three treatments at intervals of at least 7 days. Plasma histamine
      concentration, skin flushing, edema and wheals, heart rate and rhythm and non
      invasive arterial blood pressure were measured before the loading dose and at 1,
      2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI, or at the time of
      occurrence. RESULTS: The loading dose induced the highest histamine release in
      the HM group being statistically higher than the SAL group. The histamine release
      obtained in the LM group after the loading dose did not differ from SAL. During
      the infusion, plasma histamine levels were numerically higher in the LM group.
      Besides one dog that developed hypotension for 2 minutes after the loading dose
      in the HM group and one dog that showed occasional ventricular premature
      contractions during both morphine infusions, cardiovascular variables were
      similar among the three treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE:
      Both doses of morphine induced variable histamine release with minimal adverse
      cardiovascular effects in these conscious, healthy dogs. The plasma histamine
      levels obtained may be associated with significant hemodynamic changes in
      patients with limited cardiovascular reserve and sympathetic nervous tone.

PMID- 16412131
TI  - Development and verification of saphenous, tibial and common peroneal nerve block
      techniques for analgesia below the thigh in the nonchondrodystrophoid dog.
AB  - OBJECTIVE: To document simple and reliable local, infiltrating nerve blocks for
      the saphenous, tibial and common peroneal nerves in the dog. STUDY DESIGN:
      Laboratory technique development; in vivo blind, controlled, prospective study.
      ANIMALS: Twenty canine cadavers and 18 clinically normal, client-owned dogs.
      METHODS: A peripheral nerve blockade technique of the tibial, common peroneal,
      and saphenous nerves was perfected through anatomic dissection. Injections were
      planned in the caudal thigh for the tibial and common peroneal nerves, and in the
      medial thigh for the saphenous nerve. Cadaver limbs were injected with methylene
      blue dye and subsequently dissected to confirm successful dye placement.
      Clinically normal dogs undergoing general anesthesia for unrelated, elective
      procedures were randomly assigned to treatment (bupivacaine; n = 8) or control
      (saline; n = 8) nerve blocks of the nerves under study. Upon recovery from
      general anesthesia, skin sensation in selected dermatomes was evaluated for 24
      hours. RESULTS: Cadaver tibial, common peroneal, and saphenous perineural
      infiltrations were successful in nonchondrodystrophoid dogs (100, 100, and 97%,
      respectively.) Intraneural injection was rare (1%; 1/105; tibial nerve) in
      cadaver dogs. In the treatment group of normal dogs, duration of loss of
      cutaneous sensation in some dermatomes (saphenous, superficial and deep peroneal
      nerve) was significantly different than control dogs; the range of
      desensitization occurred for 1-20 hours. No clinical morbidity was detected.
      CONCLUSIONS: This technique for local blockade of the tibial, common peroneal,
      and saphenous nerves just proximal to the stifle is easy to perform, requires
      minimal supplies and results in significant desensitization of the associated
      dermatomes in clinically normal, nonchondrodystrophoid dogs. CLINICAL RELEVANCE:
      This technique may be an effective tool for post-operative analgesia to the
      femoro-tibial joint and distal pelvic limb. Other applications, using sustained
      release drugs or methods, may include anesthesia/analgesia in high-risk patients
      or as a treatment for chronic pelvic limb pain or self-mutilation.

PMID- 16412132
TI  - Controlled, clinical trial assessing saphenous, tibial and common peroneal nerve
      blocks for the control of perioperative pain following femoro-tibial joint
      surgery in the nonchondrodystrophoid dog.
AB  - OBJECTIVE: To determine whether bupivacaine peripheral nerve block of the
      saphenous, tibial and common peroneal nerves proximal to the femoro-tibial joint
      reduces peri-operative pain following extracapsular surgical stabilization of
      cranial cruciate ligament rupture in the nonchondrodystrophoid dog. ANIMALS:
      Forty-one dogs with naturally acquired femoro-tibial joint instability. Study
      design Randomized, controlled, clinical trial. METHODS: Dogs diagnosed with
      suspected cranial cruciate ligament injury based on physical and radiographic
      evidence were randomly assigned to treatment (bupivacaine) or control (saline)
      nerve blocks before femoro-tibial joint surgery. Pain scores, skin sensation,
      pain threshold to incisional pressure, time to first systemic 'rescue' opioid
      analgesic and total analgesic dose were evaluated for 24 hours. p < 0.05 was
      considered significant. RESULTS: Treatment dogs had a significantly longer period
      of cutaneous desensitization than control dogs. There were no significant
      differences between treatment and control groups for pain score, pain threshold
      to incisional pressure, or time to first-rescue analgesic. The treatment group
      received significantly more supplemental analgesics than the control group.
      CONCLUSIONS: These peripheral nerve blocks were easy to perform and resulted in
      significant desensitization of the associated nerve autonomous zones, but did not
      improve post-operative analgesia. CLINICAL RELEVANCE: Clinical benefit was not
      detected when using this technique for peri-operative pain management following
      extracapsular cranial cruciate ligament surgical stabilization.

PMID- 16412133
TI  - Effects of meloxicam on renal function in dogs with hypotension during
      anaesthesia.
AB  - OBJECTIVE: To evaluate the effects of meloxicam on renal function in dogs
      anaesthetized and rendered hypotensive with acepromazine-thiopental-isoflurane.
      ANIMALS: Eight healthy beagles, four males and four females, 25.6 +/- 19.3 months
      old and weighing 12.8 +/- 2.0 kg. MATERIALS AND METHODS: Either meloxicam
      suspension at a dose of 0.133 mL kg(-1) (0.2 mg kg(-1)) or 0.133 mL kg(-1) saline
      solution (control), were given by mouth (PO) in a randomized, cross-over fashion.
      The treatment or control was given 3 hours before anaesthesia. Dogs were sedated
      with intramuscular acepromazine 0.1 mg kg(-1). Anaesthesia was induced with
      intravenous thiopental, followed by tracheal intubation and maintenance with
      isoflurane in oxygen and air, delivered using a semi-closed breathing system.
      Renal function was quantified using serum biochemistry, urinalysis and glomerular
      filtration rate measured by scintigraphy. Analysis of variance or Friedman anova
      were used for statistical analysis. RESULTS: Values (mean +/- SD) for mean
      arterial blood pressure did not differ significantly between treatments but was
      low (54 +/- 7 mmHg) during anaesthesia. Glomerular filtration rate did not differ
      significantly between treatments or over time, and results of urine and serum
      analysis were within reference ranges after meloxicam treatment. CONCLUSIONS AND
      CLINICAL RELEVANCE: Meloxicam caused no adverse effects on renal function when
      given to healthy dogs anaesthetized and rendered hypotensive with acepromazine,
      thiopental and isoflurane.

PMID- 16412134
TI  - Effects of oxymorphone and hydromorphone on the minimum alveolar concentration of
      isoflurane in dogs.
AB  - OBJECTIVES: To quantify the change in the minimum alveolar concentration (MAC) of
      isoflurane (ISO) associated with oxymorphone (OXY) or hydromorphone (HYDRO) in
      dogs. DESIGN: Randomized crossover study with at least 1 week between
      assessments. ANIMALS: Six young, healthy, mixed-breed dogs (1-3 years old),
      weighing 24.7 +/- 4.70 kg. METHODS: Following mask induction, anesthesia was
      maintained with ISO in 100% O(2) using mechanical ventilation. The dogs received
      0.05 mg kg(-1) OXY, 0.1 mg kg(-1) HYDRO, or 1 mL saline (control) IV. Following
      equilibration (15 minutes) at each percentage ISO tested, a supramaximal
      electrical stimulus was applied to the toe web and the response was assessed. Two
      separate MAC determinations were carried out during 4.5 hours of anesthesia, with
      completion of the evaluations at 1.5-2 and 4-4.5 hours after drug administration.
      A two-factor anova was used to determine whether there was a time or treatment
      effect on MAC and a Tukey test compared the drug effects at each time.
      Significance is reported at p < 0.05. RESULTS: The mean MAC values (+/-SD) were
      1.2 +/- 0.18 and 1.2 +/- 0.16% for control, 0.7 +/-0.15 and 1.0 +/- 0.15% for
      OXY, and 0.6 +/- 0.14 and 0.8 +/- 0.17% for HYDRO. The initial MAC with OXY and
      the MAC determined at both times with HYDRO were significantly different from the
      control MAC values. CONCLUSIONS: Both OXY and HYDRO significantly reduced the MAC
      of ISO in dogs at 2 hours. At approximately 4.5 hours, HYDRO had a significant
      MAC-sparing effect, whereas OXY did not. CLINICAL RELEVANCE: Although both OXY
      and HYDRO resulted in a significant reduction in the MAC of ISO at approximately
      2 hours, HYDRO may be preferred for procedures of long duration and rarely needs
      repeated dosing before 4.5 hours.

PMID- 16412135
TI  - Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy
      and postpartum: a longitudinal study comprising 404 Danish women.
AB  - OBJECTIVE: To assess folate and homocysteine status during normal pregnancy and
      postpartum in a longitudinal setting. METHODS: This study, performed in 1995
      1996, comprised 404 healthy pregnant Danish Caucasian women residential in
      Copenhagen County. Women taking folic acid tablets or vitamin B12 injections were
      not included. Dietary multivitamin supplements containing folic acid 100 microg
      or vitamin B12 1 microg, taken by 34%, were discontinued at inclusion.
      Participants had normal renal function. Folate status [erythrocyte (Ery-) folate,
      plasma (P-) folate, P-homocysteine] was measured at 18, 32 and 39 wk of gestation
      and 8 wk postpartum when the women were lactating. RESULTS: Through 18, 32 and 39
      wk of gestation and postpartum, P-folate demonstrated a significant fall: median
      values were 14.4, 10.2, 9.3 and 8.9 nmol/L, respectively (P < 0.0001). The
      prevalence of low P-folate <6 nmol/L increased during pregnancy from 0.7% to
      19.0% postpartum (P < 0.0001). Ery-folate displayed a similar, significant fall:
      median value was 0.84, 0.75, 0.65 and 0.55 micromol/L, respectively (P < 0.0001).
      The prevalence of low Ery-folate <0.40 micromol/L increased during pregnancy from
      0.5% to 17.2% postpartum (P < 0.0001). P-homocysteine demonstrated a significant
      increase: median value was 6.4, 7.0, 7.7 and 10.8 micromol/L, respectively (P <
      0.0001). The prevalence of P-homocysteine >13 micromol/L increased during
      pregnancy from 0.7% to 20.8% postpartum (P < 0.0001). The prevalence of low
      folate status (defined as P-folate <6 nmol/L and P-homocysteine >13 micromol/L)
      was 0%, 0%, 1.2%, and 8.4% at 18, 32 and 39 wk of gestation and 8 wk postpartum,
      respectively. CONCLUSION: Low folate status occurs among Danish pregnant women,
      especially in late pregnancy and postpartum during lactation. Despite new
      guidelines for folic acid supplement since 1997, only 13% of pregnant women
      followed the guidelines in 2003. The official recommendations for
      periconceptional folic acid supplement should be reconsidered and reinforced.

PMID- 16412136
TI  - Early treatment-related mortality in adult autologous stem cell transplant
      recipients: a nation-wide survey of 1482 transplanted patients.
AB  - OBJECTIVES: To evaluate early (<100 d) treatment-related mortality (TRM) in
      autologous stem cell transplant (ASCT) recipients. PATIENTS: Altogether 1482
      adult patients received ASCT in six Finnish centres 1990-2003. The most common
      diagnoses were non-Hodgkin's lymphoma (NHL) (n = 542), multiple myeloma (MM) (n =
      528), breast cancer (BC) (n = 132), Hodgkin's lymphoma (n = 86) and chronic
      lymphocytic leukaemia (CLL) (n = 63). RESULTS: Forty-two patients (2.8%) died
      from treatment-related reasons <100 d from ASCT. The median time to death was 38
      d from ASCT (0-99). The risk of TRM varied according to the diagnoses. The
      highest risk was observed in patients with AL amyloidosis (24%) followed by NHL
      (4.4%) and MM (1.9%). No early TRM was observed in patients transplanted for BC
      or CLL. Infections were the cause of death in 16 patients (fungal 7, bacterial 6,
      viral 3). Organ toxicity was responsible for early death in 26 patients (heart 9,
      lungs 7, other 10). CONCLUSIONS: This nation-wide survey indicated a low early
      TRM in ASCT recipients in general, but higher risks in patients with AL
      amyloidosis or NHL. In addition to patient selection, also optimization of
      transplant procedure may be needed in these patient groups to reduce early TRM.

PMID- 16412137
TI  - Mutational and methylation analysis of the cyclin-dependent kinase 4 inhibitor
      (p16INK4A) gene in chronic lymphocytic leukemia.
AB  - OBJECTIVES: Chronic lymphocytic leukemia (CLL) comprises a heterogeneous group of
      at least two types of disease entities characterized by distinctive clinical,
      immunophenotypical and genetic features. The molecular mechanisms underlying the
      pathogenesis and the histological transformation of CLL are not well known. The
      INK4A/p16, a cyclin dependent kinase inhibitor has been considered as a tumor
      suppressor gene. Inactivation of this gene by homozygous deletions, mutations and
      hypermethylation occurs in a variety of human neoplasms. The aim of the present
      study was to determine the frequency of p16 gene deletions and mutations as well
      as the methylation status of the same gene in CLL patients. METHODS: We examined
      34 samples from CLL patients by Southern Blotting, Single-Strand Conformation
      Polymorphism (SSCP), DNA sequencing and Methylation-Specific PCR. RESULTS:
      Southern Blot analysis revealed non-rearranged bands in 33/34 cases. Homozygous
      deletions were not observed in any case. In 1/34 case a rearranged band was
      detected with EcoRI enzyme. The PCR-SSCP analysis of exons 1 and 3 revealed
      normal pattern of migration in all cases examined. The analysis of exon 2
      revealed abnormal migration pattern in 2/34 cases (5.8%). Sequencing of these
      cases revealed the presence of the ALA148THR polymorphism. Methylation analysis
      of p16 gene promoter revealed hypermethylation of CpG islands in 6/34 cases
      (17.6%). CONCLUSION: These results indicate that genetic alterations of p16 gene
      are rare events in patients with CLL. The clarification of the role of p16 gene
      promoter methylation in the pathogenesis and evolution of CLL needs further
      investigation.

PMID- 16412138
TI  - Idiopathic thrombocytopenic purpura (ITP) in the elderly: clinical course in 178
      patients.
AB  - Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly (age
      >or=65 yr), where it generally presents as a chronic disease. The objective of
      the present study was to describe the natural history of ITP in the elderly and
      to evaluate the risk of bleeding and the possible occurrence of other
      pathologies. We retrospectively evaluated 178 ITP patients (82 men, 96 women;
      mean age: 72 yr) diagnosed between 1981 and 1998. Therapy was started at
      diagnosis or during follow-up, depending on the platelet count and/or bleeding
      events. Sixty-six out of one hundred and seventy-eight patients (37%) initiated
      therapy at diagnosis; whereas in 11 of the 112 untreated patients (9.8%) therapy
      was necessary during the follow-up. Low-dose of prednisone was the first-line
      treatment in all patients (mean daily dose of 0.43 mg/kg). Forty-nine (63.6%) of
      the seventy-seven treated patients showed a response, 14 of these (28.6%)
      suffered a relapse. Another pathology occurred in 19 of the 178 patients (10.7%).
      We conclude that low-dose prednisone is an appropriate initial treatment for
      elderly persons. We also stress that an adequate follow-up is advisable, given
      that isolated thrombocytopenia could in some cases be the first sign of another
      underlying pathology.

PMID- 16412143
TI  - Does the band cell survive the 21st century?
AB  - OBJECTIVES: The differentiation of white blood cells is a worldwide-accepted
      method to obtain medical information. The conventional microscopic differential,
      however, is a laborious and expensive test with a low statistical value.
      Especially for band cell identification there is a wide range of variance. In
      this report we describe the intervariability of band cell enumeration. METHODS:
      From a septic patient, an EDTA anti-coagulated blood sample was obtained and a
      smear was made and stained (May-Grunwald Giemsa). A PowerPoint presentation was
      made twice of 100 random cells and sent to 157 different hospital laboratories in
      the Netherlands for a leukocyte differential. In the first survey neutrophils
      were differentiated in segmented and band neutrophils whereas in the second
      survey no discrimination was made between segmented and band neutrophils.
      RESULTS: The first survey was responded by 68% of the laboratories (756
      individuals) and the second survey by 73% of the laboratories (637 individuals).
      The laboratory mean values of the segmented neutrophils were 42.9% (SD: 7.8,
      range 22-64%) and 69.9% (SD: 1.4, range 62-72%) for the first and second survey
      respectively. For the individual technicians the values of the segmented
      neutrophils were 43.9% (SD: 11.2, range 15-72%) and 70.0% (SD: 2.0, range 59-77%)
      for the first and second survey respectively. CONCLUSIONS: Because of the
      enormous variation of band cell counting we recommend to cease quantitative
      reporting of band cells, especially since the results only have a clinical
      relevance in a limited number of pathological circumstances.

PMID- 16412147
TI  - Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis
      -part I.
AB  - Ovarian hormones have a significant effect on the central nervous system of
      female migraineurs. Reproductive milestones such as menarche, pregnancy, and
      menopause are associated with changes in the clinical course of migraine
      headache. Migraine attacks are commonly triggered during declines in serum
      estrogen levels that occur before and during the time of menstruation. Therefore,
      substantial clinical evidence suggests that changes in ovarian hormones affect
      migraine headache. This represents the first of two manuscripts defining the role
      of ovarian hormones in the pathogenesis of migraine headache. The purpose of the
      first article will be to review the molecular and neurophysiologic effects of
      estrogen and progesterone on neurotransmitter systems and pain processing
      networks relevant to migraine headache. The second manuscript will focus on the
      clinical studies detailing the influence of estrogen and progesterone on migraine
      headache.

PMID- 16412148
TI  - Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients.
AB  - BACKGROUND: Secretion of calcitonin gene-related peptide (CGRP) from trigeminal
      nerves and vasoactive intestinal peptide (VIP) from parasympathetic nerves is
      involved in the pathophysiology of migraine and rhinosinusitis. Analysis of these
      neuropeptides in human saliva samples can be used as markers of trigeminal and
      parasympathetic nerve activity in patients between and during attacks as well as
      in response to specific treatments. OBJECTIVE: To compare the amount of
      trigeminal sensory and parasympathetic nerve activation by measuring CGRP and VIP
      levels in the saliva of subjects experiencing noninfectious allergic
      rhinosinusitis, migraine with sinus symptoms, and no symptoms. METHODS: Subjects
      were enrolled in three groups. Group A: subjects without a history of migraine,
      "sinus" headache, or allergic rhinosinusitis within the previous 6 months. Group
      B: subjects with chronic recurrent noninfectious rhinosinusitis and no history of
      migraine or "sinus" headache. Group C: subjects with self-described "sinus"
      headaches whose symptoms met International Headache Society diagnostic criteria
      (1.1 or 1.2) for migraine. The total amount of CGRP and VIP present in saliva
      collected under normal, pathological, and therapeutic conditions was determined
      by radioimmunoassay. Neuropeptide levels were normalized to total volume and
      amount of protein, and levels were correlated to onset and change in clinical
      symptoms. RESULTS: Total volume, total protein, and CGRP and VIP levels did not
      significantly change in saliva collected on consecutive days in the clinic and at
      the subject's home, respectively. No appreciable change in baseline salivary
      levels of CGRP and VIP was detected in control subjects. However, baseline
      salivary levels of CGRP and VIP were significantly elevated between attacks in
      allergic rhinosinusitis and migraine subjects compared to control values. For
      rhinosinusitis subjects, the amount of CGRP and VIP during attacks returned to
      baseline values following treatment with pseudoephedrine and relief of symptoms.
      Similarly, CGRP and VIP levels during a migraine headache were significantly
      reduced within 2 hours after sumatriptan treatment and reported symptom relief.
      CONCLUSION: Correlation of CGRP and VIP saliva levels observed in our study
      supports physiologically coordinated regulation of trigeminal and parasympathetic
      nerve activation in allergic rhinosinusitis and migraine patients between and
      during attacks as well as following treatment. Furthermore, our findings
      demonstrate that analysis of human saliva neuropeptides may provide a
      semiquantitative index of pathological and therapeutic states and, therefore,
      function as a clinical model for studying neuronal mechanisms involved in
      migraine and rhinosinusitis.

PMID- 16412149
TI  - Serotonin depletion, cortical spreading depression, and trigeminal nociception.
AB  - BACKGROUND: The attack of migraine has been observed to be associated with low
      level of serotonin (5-HT). Although the mechanism underlying this relationship is
      still unclear, change in cortical excitability or susceptibility of trigeminal
      system is a possible explanation. OBJECTIVES: The aim was to study the effect of
      5-HT depletion on the development of cortical spreading depression (CSD) and CSD
      evoked trigeminal nociception. METHODS: Wistar rats were separated into low 5-HT
      and control groups (eight rats each). 5-HT was depleted by administration of para
      chlorophenylalanine, a tryptophan hydroxylase inhibitor. CSD was induced by
      applying 3 mg of potassium chloride on parietal cortex. Cortical activity was
      monitored for 1 hour. Trigeminal nociception was determined using number of Fos
      immunoreactive (Fos-IR) neurons in trigeminal nucleus caudalis as the indicator.
      RESULTS: Application of KCl led to the development of series of depolarization
      shift characteristics for CSD. The development of these CSD waves was enhanced in
      low 5-HT state. The area under curve of each CSD wave and the number of CSD waves
      occurring within 1 hour were greater in low 5-HT group. No significant change in
      peak amplitude and duration of CSD wave was observed. The numbers of Fos-IR cells
      on ipsilateral and contralateral trigeminal nucleus caudalis were significantly
      greater in the low 5-HT group than those of the controls. CONCLUSION: Our
      findings indicate that 5-HT depletion enhances CSD-induced trigeminal nociception
      by increasing the cortical excitability and sensitivity of trigeminal nociceptive
      system. These findings may provide a better understanding regarding the
      relationship between low 5-HT and clinical headaches.

PMID- 16412150
TI  - Is low blood magnesium level associated with hemodialysis headache?
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence, demographic,
      clinical features, and possible risk factors for hemodialysis headache (HDH).
      BACKGROUND: HDH has been recognized for many years, but the pathophysiology of
      this condition is not known. High arterial blood pressure, decreased serum
      osmolality, sodium washout, and high blood urea nitrogen level are reported risk
      factors for HDH. Low serum magnesium (Mg) level is known to cause some types of
      headache, including migraine (menstrual migraine in particular), tension-type
      headaches, and cluster and posttraumatic headaches. Low Mg has also been reported
      in HDH patients. METHODS: A total of 250 hemodialysis (HD) patients were
      questioned about problems with headache. Of these, 75 were diagnosed with HDH
      according to the revised International Headache Society criteria for 2003. Eighty
      age- and sex-matched HD patients without HDH were selected as a control group.
      For each HDH and control subject, arterial diastolic and systolic blood pressure,
      body weight, and serum levels of sodium, blood urea nitrogen, creatinine, and Mg
      were measured before and after one HD session. Urea reduction rate and
      ultrafiltration were determined. Serum levels of phosphorus, calcium, albumin,
      and parathormone were measured only before the session. Findings in the HDH and
      control group were statistically compared. RESULTS: As noted, 75 (30%) of the
      total 250 HD patients surveyed were diagnosed with HDH. The mean headache
      duration in this group was 5.17 +/- 5 hours. Vertex location, bilateral headache,
      dull nature, and moderate severity were the most prevalent features of HDH. There
      were no statistically significant differences between the HDH and control groups
      with respect to causes of end-stage renal disease. There were no significant
      differences between the HDH and control groups with respect to predialysis values
      for blood urea nitrogen, body weight, and arterial blood pressure (P > .05), and
      the same was true for comparisons of the postdialysis values for these
      parameters. The mean predialysis sodium level in the HDH group was higher than in
      the control group (P= .003). Both the mean predialysis and mean postdialysis Mg
      levels in the HDH group were significantly lower than the corresponding levels in
      the control group (P= .05 and P= .02, respectively). CONCLUSIONS: The results
      suggest that low blood Mg level and high blood sodium level may be risk factors
      for HDH. Magnesium supplementation may help patients with HDH whose serum Mg
      levels are found to be low.

PMID- 16412151
TI  - Subclinical left ventricular dysfunction in migraine attacks.
AB  - OBJECTIVE: The aim of the present study was to evaluate cardiac performance of
      patients with migraine attacks during the overload produced by phenylephrine
      infusion. Background.-It is known that circulatory changes occur during migraine.
      However, the relationship between this finding and transient cardiac dysfunction
      is still unknown. METHODS: By means of two-dimensional direct M-mode
      echocardiography, we measured fractional shortening, ejection fraction, and mean
      velocity of circumferential fibers shortening in 18 patients with migraine and in
      10 normal subjects as a control group. These measures were performed in two
      different periods: during attack-free intervals and during attacks. Pain
      intensity of typical migraine attack was evaluated on a 0 to 10 scale. RESULTS:
      Cardiac size and function were normal at rest in both groups. However, during
      migraine attacks, phenylephrine infusion provoked significant decrease in
      fractional shortening, EF, and mean velocity of circumferential fibers
      shortening, followed by concomitant increase of headache severity. On the other
      hand, during the attack-free interval and in the control group phenylephrine
      infusion did not show significant changes in cardiac function parameters.
      CONCLUSIONS: Our data suggest that left ventricular dysfunction during the
      phenylephrine test could participate in the complex pathophysiological mechanism
      of migraine attacks.

PMID- 16412152
TI  - Gastric stasis in migraine: more than just a paroxysmal abnormality during a
      migraine attack.
AB  - OBJECTIVE: The aim of this article is to evaluate gastric motility and emptying
      in the ictal and interictal period in migraine. BACKGROUND: Nausea is a
      predominant symptom of migraine and the basis of it is thought to be gastric
      stasis. Objective methods to establish this are however lacking. We utilized
      gastric scintigraphy studies to determine gastric motility in the ictal and
      interictal period of migraine. METHODS: Ten migraine subjects were compared to
      equal number of age and sex matched controls. Gastric scintigraphy using a
      standard meal was performed in all control subjects once and in all 10 migraine
      subjects in the interictal period and nine studies were performed in the ictal
      period migraine. RESULTS: The time to half emptying was delayed in migraine
      ictally (78%) and interictal period (80%) using normative data at this
      institution. Gastric stasis was less pronounced ictally (149.9 minutes) compared
      to interictal period (188.8 minutes). There was a significant delay compared to
      nonmigrainous controls (migraine 188.8 minutes vs normal controls 111.8 minutes;
      P < .05). These data were replicated in percentage of radioactive material
      remaining in the stomach at 2 hours. CONCLUSIONS: Contrary to previous belief,
      this study has demonstrated that migraineurs suffer from gastric stasis both
      during and outside an acute migraine attack. This may suggest that migraineurs
      may have an abnormal autonomic function compared to nonmigrainous controls. The
      potential role of this in pathophysiology of migraine is discussed and avenues
      for further investigations are explored.

PMID- 16412153
TI  - Weather and emergency room visits for migraine headaches in Ottawa, Canada.
AB  - BACKGROUND: Self-reported surveys have indicated that weather can trigger
      migraine headaches. However, to date, we know of no previous study that has
      examined the relationship between weather and emergency room (ER) visits for this
      condition. OBJECTIVE: To examine associations between ER visits for migraines and
      selected meteorological conditions within the 24 hours preceding the visit.
      DESIGN AND METHODS: A case-crossover design was used to study 4039 visits for
      migraines (ICD-9: 346) that occurred at an Ottawa hospital between 1993 and 2000.
      Meteorological conditions were defined using hourly readings from a fixed-site
      monitoring station. Conditional logistic regression was used to compare the
      occurrence of meteorological conditions during the 24 hours leading up to the
      time of the visit to control periods occurring 1 week before and after. RESULTS:
      Precipitation-related weather events (fog, snow, rain, thunder) were not
      associated with migraine visits. Similarly, no associations were observed with
      changes in atmospheric pressure, wind speed, and relative humidity during the 24
      hours preceding presentation. No statistically significant differences in the
      frequency distribution of clusters defined by relative humidity, atmospheric
      pressure, and temperature were found between case and control intervals.
      Conversely, a mean wind speed in excess of 19 km per hour was associated with a
      reduction in ER visits 8 to 12 hours later. CONCLUSIONS: Our findings provide
      little support for the hypothesis that ER visits for migraines are related to
      weather conditions occurring within the 24 hours preceding presentation. These
      results should be interpreted cautiously as some comparisons are based on a small
      number of cases, and ER visits for migraine may represent a highly selective
      group of patients who suffer from this condition.

PMID- 16412154
TI  - Recurrent headache and migraine as a public health problem--a population-based
      study in Sweden.
AB  - OBJECTIVE: To study the prevalence of recurrent headache and/or self-considered
      migraine (RH/M) and its association with self-rated health, other symptoms, and
      use of health care and medication in the general population. METHODS: The study
      comprised a random population sample of 43,770 men and women aged 18 to 79 years
      covering an area of 58 municipalities in Sweden. The data were obtained using a
      postal survey questionnaire during March to May 2000. The overall response rate
      was 65%. RESULTS: The overall prevalence of self-reported RH/M was 10% among men
      and 23% among women. RH was more common (15%) than migraine (4%). The prevalence
      of RH was highest in the younger age groups (18 to 34 years) and decreased with
      increasing age. The prevalence of migraine was highest (6%) among 35 to 49 years
      old. Subjects with RH/M had poorer self-rated health compared to subjects with no
      reported headache independent of age. Poor self-rated health was most common
      among subjects with both RH and M. Musculoskeletal pain and psychosomatic
      symptoms were more common among those with RH/M. The association between RH/M and
      poor self-rated health was partly explained by these symptoms. Those with RH/M
      utilized more health care at all levels than those with no RH/M. In addition,
      subjects with RH/M reported two to three times more often that they had been in
      need of medical care but not sought it. About two-thirds of the subjects with
      RH/M had used analgesic during the last 2 weeks compared with less than one-third
      among subjects with no RH/M. CONCLUSION: RH/M constitutes a substantial public
      health problem that mainly affects young and middle aged adults. It is associated
      with poor self-rated health, musculoskeletal and psychosomatic symptoms,
      increased use of health care and medication as well as unmet needs of health
      care.

PMID- 16412155
TI  - Translating instruments for cross-cultural studies in headache research.
AB  - OBJECTIVE: To describe translation methods, to outline current recommendations
      for translation and to give an overview of translation procedures used in
      headache. BACKGROUND: In health-care research, particularly in the domain of
      health-related quality of life, an increasing number of questionnaires are
      translated for cross- cultural comparison. A number of headache-related
      questionnaires have also been translated. To ensure true cross-cultural
      comparison, it is important to use rigorous translation methods to ensure a high
      quality translated version of the instruments. METHODS: Literature relevant to
      cross-cultural translations was reviewed, as well as literature concerning
      translation of headache-related instruments. CONCLUSION: More information on the
      translation process for headache-related instruments is essential to carry out
      high quality cross-cultural research. Recommendation are given to encourage good
      translation practices.

PMID- 16412156
TI  - Effects of a Website designed to improve the management of migraines.
AB  - OBJECTIVE: The aim was to examine the effect of using a Web-based computer
      program that provides personalized feedback to migraine patients, on the
      interactions of patients and providers. Background.-Despite the widespread
      availability of evidence-based migraine treatment guidelines, patients often do
      not receive optimal treatment to reduce migraine pain and disability. METHODS: To
      address these quality gaps in migraine care, we developed a Web-based computer
      program, to be used by migraine patients before doctor visits. The feedback is
      designed to prompt patients to ask questions that lead to higher quality of care.
      This study was conducted to examine the effect of using the program on migraine
      specific doctor-patient communications. Patients were randomized to use the
      Website before (intervention) or after (control) a visit with their provider. The
      outcome measures were the migraine-specific topics discussed during the visit,
      measured by an exit survey after the visit. RESULTS: Fifty of 53 subjects
      randomized completed the postvisit measures (94%). Overall, the mean age was 42.0
      years, most patients were female (86.5%), all were white, and 58.5% saw a
      headache specialist during their visit. Most (75.0%) reported having headaches at
      least once per week and 48.1% rated their headaches as "severe." Intervention
      patients were significantly more likely to "discuss whether you had migraine
      headaches or some other type of headache?" (89.3% vs 54.5%; P < .01) and to
      "discuss whether or not there may be a more serious cause of your headaches?"
      (50.0% vs 13.6%; P < .01). Intervention patients were more likely to report
      discussing 8 of 12 migraine-related topics more frequently and a greater overall
      number of topics (5.5 vs 4.3) than control patients. This difference was not
      statistically significant. CONCLUSIONS: These results suggest that the Website
      may have a positive impact on migraine-specific doctor-patient communications. A
      larger study, including important quality of life and utilization outcomes, is
      warranted.

PMID- 16412157
TI  - Zolmitriptan oral tablet in migraine treatment: high placebo responses in
      adolescents.
AB  - OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled
      study was to evaluate the efficacy and tolerability of the zolmitriptan
      conventional tablet at three different doses for the treatment of a single
      migraine attack in adolescents. BACKGROUND: Preliminary data from an open-label
      study suggested that the zolmitriptan conventional tablet could be effective in
      the treatment of acute migraine in adolescent patients. METHODS: Migraine
      patients aged 12 to 17 years (n = 850) were randomized to receive zolmitriptan
      2.5, 5, or 10 mg, or placebo for treatment of a single migraine attack. Patients
      recorded migraine headache intensity before and after treatment using a 4-point
      scale. RESULTS: There was no statistically significant improvement between
      zolmitriptan 10 mg (2 x 5 mg tablet) and placebo for the primary efficacy
      variable, headache response at 2 hours, nor any of the secondary variables
      tested. Two-hour headache response rates were 54%, 53%, and 57% for zolmitriptan
      10, 5, and 2.5 mg, respectively, and 58% for placebo. Two-hour pain-free rates
      were 25%, 19%, and 23% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 20%
      for placebo. Zolmitriptan was well tolerated, with a tolerability profile similar
      to the pattern seen in adults. CONCLUSION: The similar efficacy between
      zolmitriptan and placebo appears to be the result of the high placebo response
      rate. This is a recognized issue in pediatric migraine studies and there is an
      ongoing debate on ways to address this problem. Since this study was initiated,
      there has been some debate on the appropriateness of the 2-hour endpoint for
      response rates in adolescent studies, given the shorter duration of headache pain
      in adolescents compared with adults. Furthermore, accurate information regarding
      the timeliness of treatment and reporting of headache-related information by
      adolescents is difficult.

PMID- 16412158
TI  - Cusums to measure chronic daily headache.
AB  - OBJECTIVE: To investigate whether cumulated summed differences (cusums) can be
      used as a method for detecting effective interventions in chronic daily headache
      (CDH). If so, then can such interventions be detected sooner than 28 days?
      BACKGROUND: CDH probably represents the greatest current challenge in the field
      of headache treatment. Clinical trial methodologies for its study are not
      standardized but usually use fixed 28-day observation periods. Similarly, 28-day
      observation periods are common review intervals for stepped-care patient
      management strategies. METHODS: A theoretical patient was modeled, with daily
      headache scores that had maximal variation for 28 consecutive daily measures. The
      cusums for this "norm" or control data set were plotted and correlated with time
      using a simple spreadsheet. Departure of a postintervention cusum from the 95%
      confidence interval of the control data set was chosen as an indicator of
      sensitivity to various model perturbations that had clinical correlates. RESULTS:
      When 1 to 17 randomly distributed headache-free days were used to perturb the 28
      day model, cusums consistently diverged from the norm. If at least 3 headache
      free days occurred, then the cusum detected the intervention in less than 28 days
      of observation. Reanalysis of a previously published study of magnesium oxide
      suggests that its negative conclusions should be reconsidered. CONCLUSION: Cusums
      can be useful tools for detecting change in CDH, whether at the level of the
      clinical trial or when managing patients using stepped-care treatment algorithms.

PMID- 16412159
TI  - Oral sumatriptan for the acute treatment of probable migraine: first randomized,
      controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in
      adults who meet International Headache Society (IHS) criteria for probable
      migraine but who do not meet IHS criteria for migraine with or without aura.
      BACKGROUND: Headaches with some but not all of the features of migraine meet
      criteria for probable migraine, a form of migraine recognized by the IHS.
      Probable migraine attacks are also prevalent and frequently underdiagnosed.
      METHODS: This was a randomized, multicenter, double-blind, placebo-controlled,
      parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches
      that met 2004 IHS criteria for probable migraine without aura (same operational
      definition as 1988 IHS migrainous disorder) were eligible for enrollment. All
      patients were triptan- and ergot-naive and had never been diagnosed with
      migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan
      25, 50, or 100 mg conventional tablets or matching placebo and were instructed to
      treat a single moderate or severe probable migraine attack. A post hoc analysis
      was conducted to evaluate the population of patients who achieved headache relief
      sustained throughout the immediate posttreatment period. Patients who reported
      relief within 2 hours and subsequently lost headache relief within 4 hours were
      considered nonresponders. RESULTS: At 2 hours, more patients treated with
      sumatriptan achieved headache relief, the primary efficacy measure, compared with
      placebo, but differences only approached statistical significance for 100 mg (P=
      .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was
      not significantly different than placebo. The time to use of rescue was
      significantly shorter in the placebo group compared with the sumatriptan 100 mg
      group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups
      was not significantly different than placebo. More patients treated with placebo
      (22%) lost headache relief within 4 hours compared with patients treated with
      sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis
      demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4
      hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25,
      50, and 100 mg, respectively, compared with 34% of patients treated with placebo
      (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan
      were well tolerated and no serious adverse events were reported. CONCLUSION:
      These results suggest that oral sumatriptan may be effective and is well
      tolerated for the acute treatment of probable migraine without aura, however, the
      difference between sumatriptan and placebo was not statistically significant for
      the a priori defined primary endpoint.

PMID- 16412160
TI  - Symptoms of premenstrual syndrome and their association with migraine headache.
AB  - OBJECTIVES: To determine the association between the severity of premenstrual
      (PMS) symptoms and headache outcome measures during natural menstrual cycles and
      after medical oophorectomy. BACKGROUND: Premenstrual syndrome may occur in 64% of
      those with pure menstrual migraine and 33% of those with menstrually related
      migraine. Few past studies have examined the relationship between the severity of
      PMS symptoms and migraine headache. METHODS: Data were obtained from a 6.5-month
      randomized-controlled trial examining the role of medical oophorectomy in the
      prevention of migraine headache and later divided into two data sets for analysis
      purposes. The menstrual cycle data set was composed of data from three natural
      menstrual cycles obtained from 21 participants during lead-in and placebo run-in
      phases. Each menstrual cycle was subdivided into seven 3-day intervals based on
      urine hormone metabolites. The medical oophorectomy data set included data from a
      2-month treatment period in which a medical oophorectomy was induced by
      gonadotropin-releasing hormone agonists (GnRHa) and participants were randomized
      to transdermal estradiol or a matching placebo (GnRHa/estradiol and GnRHa/placebo
      groups, respectively). All participants completed a daily diary recording the
      severity of PMS symptoms and headache outcome measures. The primary outcome
      measures were the PMS index (mean of the daily PMS severity scores) and the
      headache index (mean of the headache severity scores). Pearson correlation
      coefficients were used to assess the degree of association between the outcome
      measures. RESULTS: Menstrual Cycle Data Set.-The PMS index was significantly
      correlated with the headache index during native menstrual cycles (correlation
      coefficient of 0.47; P < .05) and during all seven intervals of the menstrual
      cycle (correlation coefficients of 0.39 to 0.65; all P values < .05). Medical
      Oophorectomy Data Set.-Correlation coefficients between the PMS and headache
      indices were 0.58 and 0.47 for the GnRHa/estradiol (n = 9) and GnRHa/placebo
      groups, respectively (P-values of <.05). CONCLUSIONS: Moderate correlations exist
      within female migraineurs between the severity of PMS symptoms and headache
      outcome measures throughout natural menstrual cycles as well as after medical
      oophorectomy. Our data would suggest that the presence and severity of headache
      might modulate PMS symptoms in female migraineurs.

PMID- 16412161
TI  - Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy.
AB  - Migraine is a common disabling neurological disorder, associated with headache,
      nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin
      5HT(1B/1D) receptor agonist with a long track record in clinical studies and in
      the treatment of acute migraine. A nasal formulation has been developed that has
      clear evidence for local absorption, resulting in plasma drug concentrations
      within 2 minutes of dosing, central nervous system penetration 3 minutes later,
      and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing.
      Intranasal zolmitriptan offers advantages to migraineurs, particularly those
      seeking a more rapid onset of effect without wishing to self-inject, or those
      with gastrointestinal upset. The comparison of pharmacokinetic and clinical data
      available from different formulations of zolmitriptan contributes both to the
      understanding of its mode of action and the characteristics required of an acute
      migraine treatment if it is to meet patient needs.

PMID- 16412162
TI  - Jugular compression and radionuclide cisternographic patterns in patients with
      chronic headache.
AB  - OBJECTIVE: We investigated the value of the jugular compression test (JCT) in
      screening patients with chronic headache attributable to persistent cerebrospinal
      fluid (CSF) leakage. METHODS: Clinical records of 35 consecutive patients who
      underwent both 111In-diethylenetriamine pentaacetic acid radioisotope (RI)
      cisternography and JCT were retrospectively analyzed. RESULTS: A strong
      correlation was seen between JCT and RI cisternographic findings. Most patients
      who reported a feeling of fullness in the ear, hearing loss or headache during
      JCT had positive findings on RI cisternograms indicative of CSF leakage. In
      contrast, no RI study abnormalities were seen in patients reporting no symptoms
      in JCT. CONCLUSIONS: Among patients complaining of refractory headache and other
      miscellaneous symptoms, JCT may represent a simple, economic, and reliable
      technique in the screening of candidates for RI cisternography to evaluate CSF
      leakage. A subgroup of patients with chronic headache may have persistent CSF
      leakage.

PMID- 16412163
TI  - Images from headache: the "dots and blots" conundrum.

PMID- 16412164
TI  - Target doses and titration schedules for migraine preventive medications.

PMID- 16412165
TI  - Exertional headache and coronary ischemia despite normal electrocardiographic
      stress testing.
AB  - Exertional headaches may under certain conditions reflect coronary ischemia. We
      report the case of a patient seen in a neurology referral practice whose
      exertional headaches, even in the face of two normal electrocardiographic stress
      tests and in the absence of underlying chest pain were the sole symptoms of
      coronary ischemia as detected by Tc-99m Sestamibi testing SPECT stress testing.
      Stent placement resulted in complete resolution of headaches. Exertional headache
      in the absence of chest pain may reflect underlying symptomatic coronary artery
      disease (CAD) even when conventional electrocardiographic stress testing does not
      indicate ischemia.

PMID- 16412166
TI  - Use of lamotrigine in glossopharyngeal neuralgia: a case report.
AB  - We describe a case of a patient with glossopharyngeal neuralgia (refractory to
      treatment with carbamazepine, amytriptyline, diazepam, and indomethacin) treated
      with lamotrigine as monotherapy, the first described, who responded completely to
      the therapy and did not complain of side effects. The complete analgesic effect
      was reached at the lamotrigine daily dose of 200 mg per day and was maintained at
      that dose for additional 6 months, with the blood concentration within the
      reference range.

PMID- 16412167
TI  - Solitary fourth ventricular neurocysticercosis presenting as status migrainosus.
AB  - Fourth ventricular cysts in patients with neurocysticercosis are generally
      solitary without accompanying parenchymal cysts and hence present with
      hydrocephalic symptoms at the time of implantation. We report a patient with
      status migrainosus-like presentation in whom the neurological examination was
      normal and the diagnosis was made by imaging (CT and MRI scan).

PMID- 16412168
TI  - Sildenafil can trigger cluster headaches.
AB  - Phosphodiesterase-5 inhibitors commonly trigger migraines but rarely trigger
      cluster headaches. Two cases of cluster headaches triggered by sildenafil are
      described.

PMID- 16412169
TI  - Fatal paranasal sinusitis presenting as trigeminal neuralgia.
AB  - Trigeminal neuralgia is rare in patients with paranasal sinusitis. The authors
      describe a case of paranasal sinusitis that appeared as an insidious onset of
      trigeminal neuralgia along the distribution of ophthalmic and maxillary branches,
      followed by rapid intracranial invasion with temporal meningoencephalitis and
      subdural empyema, and finally a fatal outcome.

PMID- 16412170
TI  - Cluster headache in a ninety-one-year-old woman.

PMID- 16412171
TI  - The risk of vasovagal syncope to family and friends observing a lumbar puncture.

PMID- 16412172
TI  - Amphetamine, migraine, and brain noradrenergic activation: contradictions in
      headache research.

PMID- 16412174
TI  - Can ketosis help migraine sufferers? A case report.

PMID- 16412176
TI  - The reliability of echocardiographic left ventricular wall motion index to
      identify high-risk patients for multicenter studies.
AB  - OBJECTIVE: To study whether the use of echocardiographic left ventricular (LV)
      wall motion index (WMI) is a dependable parameter for identifying patients with
      LV dysfunction to be enrolled in multicenter trials. METHODS: Videotaped
      echocardiographic examinations from 200 randomly selected patients that were
      screened for inclusion into the DIAMOND-CHF and DIAMOND-MI trials were
      reevaluated by an external expert echocardiographer. WMI was calculated using the
      16-segment LV model. RESULTS: The external echocardiographer systematically found
      lower values of WMI than the core laboratory. The average difference in WMI was
      0.18 (SD: 0.33) in the DIAMOND-CHF trial and 0.09 (SD: 0.33) in the DIAMOND-MI
      trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials.
      The cutoff value for inclusion into the DIAMOND trials was WMI < or = 1.2. There
      was an agreement on WMI dichotomized to below or above 1.2 in 82% of the patients
      in both trials (kappa coefficient 0.66 for the DIAMOND-CHF and 0.55 for the
      DIAMOND-MI). CONCLUSIONS: Despite substantial interlaboratory variation in WMI in
      individual patients and a systematic lower WMI score by the external
      echocardiographer there was an acceptable overall agreement for identifying
      patients with severe impairment of LV function. This not only underscores the
      value of LV-WMI as a useful tool for selecting high-risk patients to be included
      in multicenter studies but also serves to warn against the use of rigid cutoff
      values for WMI in the treatment of individual patients.

PMID- 16412177
TI  - An echocardiographic left ventricular wall area index for functional detection of
      myocardial injury in hemodynamically unloaded hearts.
AB  - Functional assessment of the left ventricle is affected by loading conditions.
      Detection of rejection-mediated myocardial injury in a heterotopic heart
      transplant model is a challenge for the echocardiographer because the heart is in
      an unloaded state. We examined the relationship of a novel left ventricular (LV)
      wall area index (LVWAI) and serum cardiac troponin T (cTnT) levels. The LVWAI,
      based on prior methods of determining LV mass, was defined as the difference
      between epicardial and endocardial areas divided by the epicardial area. The
      biphasic morphometric response of LVWAI reflected changes in the cTnT levels and
      allowed echocardiographic detection of myocardial injury in hemodynamically
      unloaded hearts.

PMID- 16412178
TI  - Myocardial systolic activation delay in patients with left bundle branch block
      and either normal or impaired left ventricular function.
AB  - AIM OF THE STUDY: to evaluate determinants of myocardial activation delay of both
      left (LV) and right (RV) ventricle in patients with left bundle branch block
      (LBBB) and either normal or impaired LV ejection fraction (EF). METHODS: From an
      initial cohort of patients with LBBB, 42 patients with dilated cardiomyopathy
      (group A) and 33 with normal global LV systolic function (group B), all
      comparable in age and sex, underwent standard Doppler echo, pulsed Doppler
      myocardial imaging (DMI), and coronary angiography. Using DMI, the following
      regional parameters were evaluated in five different basal myocardial segments
      (LV anterior, inferior, septal, lateral walls-RV lateral wall): systolic (Sm),
      early- and late-diastolic (Em and Am) peak velocities. As index of myocardial
      systolic activation was calculated: precontraction time (PCTm) (from the
      beginning of Q-wave of ECG to the onset of Sm). Intraventricular systolic
      dyssynchrony was analyzed by difference of PCTm in different LV myocardial
      segments. Interventricular activation delay was calculated by the difference of
      PCTm between the most delayed LV segment and RV lateral wall. RESULTS: Patients
      of group A showed increased heart rate (HR), QRS duration and LV end-diastolic
      diameter, and reduced LV EF. By DMI, patients of group A showed reduced
      myocardial peak velocities and a significant intraventricular delay in activation
      of LV lateral wall, with increased regional PCTm (P < 0.001). In addition,
      patients with dilated cardiomyopathy showed a more pronounced interventricular
      dyssynchrony, even after adjustment for HR and QRS duration. By receiver
      operating characteristic (ROC) curve analysis, a cut-off value of 55 msec of
      interventricular delay showed 86% sensitivity and 92% specificity in identifying
      patients with impaired EF. In the overall population, by use of stepwise forward
      multivariate linear regression analyses, LV end-diastolic diameter (beta
      coefficient = 0.52; P < 0.001) and LV EF (beta coefficient =-0.58; P < 0.0001)
      were the only independent determinants of interventricular activation delay.
      CONCLUSIONS: Pulsed DMI is an effective noninvasive technique for assessing the
      severity of regional delay in activation of LV walls in patients with LBBB. The
      impairment of interventricular systolic sychronicity is strongly related to LV
      dilatation and to the degree of global systolic dysfunction. Therefore, patients
      with dilated cardiomyopathy suitable for cardiac resynchronization therapy may be
      better selected.

PMID- 16412179
TI  - Left atrial size is a poor predictor of pathology in the older patient:
      preliminary observations.
AB  - OBJECTIVE: The goal of this study was to determine the relationship between left
      atrial (LA) size and pathology in humans. METHODS: We evaluated 14 patients (age
      60 +/- 14 years, range 25-77, 9 males) who had died at our hospital. Eight
      patients were in sinus rhythm, 3 had paroxysmal atrial fibrillation (PAF), and 3
      were in established atrial fibrillation (AF). LA size was calculated at
      transthoracic echocardiography (TTE) prior to death. At autopsy, histology of the
      dissected LA was examined at the appendage (APP), transverse sinus (TS), oblique
      sinus (OS), crux, and oval fossa. The severity of hypertrophy (HTY) and fibrosis
      (FIB) was determined by histochemistry. RESULTS: Mean LA weight was 37 +/- 11 g.
      One patient with PAF had amyloid. LA size by TTE was associated with LA weight (R
      = 0.6, P = 0.029). Increased age was associated with less severe APP FIB (P =
      0.04). Younger patients tended to have less severe APP HTY (P = 0.09), and TS FIB
      (P = 0.12). Severity of atrial HTY and FIB was similar in APP and TS (P = NS).
      There was no relationship between abnormal atrial histology with LA volume or
      cardiac rhythm. Five patients had LA dilatation (LA end systolic volume index >30
      ml/m(2)). Of those patients with normal LA size, 6 (75%) had APP FIB, 8 (100%)
      had APP HTY, 7 (88%) had TS FIB, 8 (100%) had TS HTY, and 7 (88%) had OS HTY.
      CONCLUSIONS: Abnormal LA histology is common in patients who have normal LA size
      by TTE. Microscopic atrial disease is associated with aging, and may represent a
      precursor state for LA dilatation or AF.

PMID- 16412180
TI  - Low-dose dobutamine stress echocardiography to predict reversibility of mitral
      regurgitation with CABG.
AB  - The optimal management of moderate (grade 2-3+) ischemic mitral regurgitation
      (MR) in patients undergoing coronary artery bypass grafting (CABG) remains
      controversial. While CABG alone can reverse regurgitation in some patients with
      moderate MR, adjunctive mitral repair may be necessary in others. We performed
      low-dose dobutamine stress echocardiography (DSE) in 60 patients with moderate MR
      who were about to undergo CABG. Group I, 25 patients who demonstrated reduction
      in MR during DSE, had CABG alone. Group II, 35 patients in whom MR was unchanged
      during DSE, had mitral valve repair as well as CABG. MR was reduced
      postoperatively in both groups (P < 0.0001). Postoperative ejection fraction in
      Group I (12.2%) improved more than that in Group II (9.3%) (P < 0.01). We
      conclude that CABG alone may be sufficient to correct moderate MR when MR is
      reduced during DSE.

PMID- 16412182
TI  - Early experience with real-time three-dimensional echocardiographic guidance of
      right ventricular biopsy in children.
AB  - BACKGROUND: Right ventricular endomyocardial biopsy is the gold standard for
      detecting active myocardial inflammation in cardiomyopathy as well as rejection
      after cardiac transplantation. This procedure has historically required the
      exclusive use of fluoroscopic guidance to guide catheter, sheath, and bioptome
      manipulation. The current study evaluates the feasibility and utility of real
      time transthoracic three-dimensional echocardiography (3DE) to guide right
      ventricular endomyocardial biopsies in children. METHODS: From July 2003 to April
      2004, we utilized real-time 3DE in 28 consecutive cardiac catheterizations in
      children aged 18 months to 16 years who were undergoing endomyocardial biopsy. A
      commercially available 3DE scanner (Philips Sonos 7500) equipped with a 2-4 MHz
      3D matrix array transthoracic probe was utilized in all cases. RESULTS: A total
      of 123 endomyocardial biopsy samples were obtained in nine patients (BSA 0.85
      m(2)+/- 0.33 m(2)). Of these 123 samples, 99 (80%) were obtained with the use of
      real-time transthoracic 3DE. There were no complications, including no new
      tricuspid valve leaflet flail or pericardial effusion. 3DE proved to be a
      reliable noninvasive modality to properly direct the bioptome to the desired site
      of biopsy within the right ventricle. As familiarity with this technique
      increased, the need for fluoroscopic guidance of bioptome manipulation in the
      right ventricle was minimized. CONCLUSIONS: The use of real-time transthoracic
      3DE in endomyocardial right ventricular biopsies in children is both feasible and
      safe. Further study to determine the impact of real-time 3DE guidance on
      fluoroscopy and case times for endomyocardial biopsies is warranted.

PMID- 16412181
TI  - Diastolic function in young patients with beta-thalassemia major: an
      echocardiographic study.
AB  - OBJECTIVE: We aimed to evaluate myocardial diastolic function in patients with
      beta-thalassemia major (beta-TM) using pulsed-tissue Doppler imaging (TDI) and
      flow propagation (VP), in relation to BNP levels. METHODS: We enrolled 192
      consecutive patients with beta-TM (88 men (25 +/- 6 years) and 104 women (26 +/-
      6 years), with normal left ventricular (LV) systolic function. By TDI, diastolic
      myocardial velocities were sampled at the lateral section of the mitral annulus
      (Smv, Emv, Amv). From the apical four-chamber view diastolic transmitral flow
      velocities, including measures of E- and A-waves were performed. The propagation
      velocity of early flow into the LV cavity was measured by color M-mode Doppler.
      Plasma BNP levels were measured in all patients. RESULTS: A nonlinear
      relationship was found between BNP levels and E/A ratio (beta coefficient for the
      second-order term = 1.4 +/- 0.4, P = 0.001). We also found a positive association
      of BNP levels with Amv (r = 0.28, P = 0.023), and a reverse with Smv (r =-0.59, P
      = 0.01) and Emv/Amv (r =-0.36, P = 0.019). Moreover, an inverse relationship was
      observed between BNP and Vp (r =-0.43, P = 0.012) levels. Finally, a strong
      positive linear relationship was found between E/Vp ratio and BNP levels (r =
      0.76, P < 0.001). CONCLUSION: A U-curved association of E/A ratio of transmitral
      Doppler velocity was revealed with BNP levels, while the tissue Doppler of the
      Emv/Amv of the mitral annulus movement showed a negative linear association with
      BNP levels.

PMID- 16412183
TI  - Idiopathic dilatation of right atrium with atrial standstill presenting as
      stroke.
AB  - A 48-year-old lady presenting with stroke was found to have idiopathic dilatation
      of right atrium with atrial standstill.

PMID- 16412184
TI  - Increased mitral regurgitation during the valsalva maneuver in a patient with
      pheochromocytoma, uncontrolled hypertension, cardiac hypertrophy, and dynamic
      outflow tract obstruction.
AB  - Dynamic left ventricular outflow tract obstruction is a common feature of
      hypertrophic cardiomyopathy, but it can also be demonstrated in other conditions
      that result in increased thickness of the left ventricular septal wall. Severe
      uncontrolled hypertension may lead to severe hypertrophy of the left ventricle
      and produce systolic anterior motion of the mitral valve and an outflow gradient.
      We report a case of pheochromocytoma with echocardiographic demonstration of
      markedly increased mitral regurgitation during the Valsalva maneuver in a patient
      with left ventricular hypertrophy and a dynamic outflow tract obstruction.

PMID- 16412185
TI  - Echocardiographic detection of intrapulmonary shunting in a patient with
      hepatopulmonary syndrome: case report and review of the literature.
AB  - Transthoracic echocardiography is a useful tool in the evaluation of patients
      with intrapulmonary and intracardiac shunts. We describe a case of a 49-year-old
      female with severe hypoxemia in the setting of aortic stenosis and cirrhosis of
      the liver. The use of agitated saline contrast during an echocardiography study
      helped to establish the diagnosis of intrapulmonary arteriovenous shunting
      consistent with the hepatopulmonary syndrome, thereby confirming the etiology of
      her symptoms and laboratory findings. This case report highlights the utility of
      echocardiography in diagnosing intrapulmonary shunts and assists in the
      understanding of the pathophysiology of hypoxemia in such patients.

PMID- 16412186
TI  - A continuous murmur.
AB  - A 61-year-old male with a history of a mechanical Bjork-Shiley aortic valve
      replacement in 1977 and repair of an ascending aortic root dissection in 1993,
      presented with a 2-week history of fatigue and exertional dyspnea.
      Echocardiography confirmed the presence of an aortic pseudoaneurysm with a
      fistulous connection between the aorta and right atrium, which subsequently
      underwent successful repair. Although there have been several cases describing
      the development of an aortic pseudoaneurysm after aortic dissection repair, our
      case is the first to describe an aorta-atrial fistula as a long-term complication
      of a previous aortic dissection repair.

PMID- 16412187
TI  - Coronary to pulmonary artery fistula--diagnosis by transesophageal
      echocardiography.
AB  - Coronary artery fistulas (CAFs) are rare coronary anomalies which generally
      require coronary angiography for definitive diagnosis. CAFs most commonly drain
      into the right atrium or right ventricle, but occasionally can drain into the
      pulmonary artery. We report the case of an asymptomatic coronary to pulmonary
      artery fistula, which could only be definitively diagnosed with transesophageal
      echocardiography.

PMID- 16412188
TI  - Echocardiographic diagnosis of obstructed supracardiac total anomalous pulmonary
      venous connection.
AB  - Obstruction in supracardiac total anomalous pulmonary venous connection (TAPVC)
      may be seen in 50% of cases. We describe here successful echocardiographic
      diagnosis of obstruction at an unusual and undescribed location in a supracardiac
      TAPVC. The patient was successfully managed by surgery.

PMID- 16412189
TI  - Incremental value of live/real time three-dimensional transthoracic
      echocardiography in the assessment of left ventricular thrombi.
AB  - This is a case series on three adult patients who contain left ventricular (LV)
      thrombus and the incremental benefits of live/real time three-dimensional
      transthoracic echocardiography (3DTTE) in comparison to two-dimensional
      transthoracic echocardiography (2DTTE) in evaluating LV thrombi. These cases
      illustrate that 3DTTE is of additional benefit by demonstrating the following:
      (1) cropping of a single 3DTTE apical dataset may be enough to provide
      comprehensive assessment of the LV in a timely manner even without breath holding
      in a not fully cooperative patient (2) it identifies the exact point of
      attachment of the thrombus to the left ventricular wall, (3) helps to delineate
      the absence or presence of focal echolucent areas within thrombi indicative of
      the presence and extent of clot lysis, which may have potential therapeutic and
      prognostic implications, and (4) provides more accurate assessment of thrombus
      mobility which has prognostic indications.

PMID- 16412190
TI  - Acquired isolated left pulmonary vein stenosis: a complication of bronchogenic
      cyst removal diagnosed by transesophageal echocardiography.

PMID- 16412191
TI  - Bioprosthetic valve thrombosis.

PMID- 16412192
TI  - Effect of left ventricular systolic pressure on myocardial strain demonstrated by
      transmural myocardial strain profile.

PMID- 16412193
TI  - Intracardiac fibroma in nevoid-basal cell carcinoma (gorlin) syndrome: tissue
      characterization by strain rate imaging.

PMID- 16412194
TI  - Three-dimensional transthoracic echocardiographic visualization of a voluminous
      left atrial thrombus.

PMID- 16412195
TI  - Routine screening for abdominal aortic aneurysm in the echocardiography
      laboratory using a "modified" abdominal aortic examination protocol.

PMID- 16412197
TI  - Closeness and distance in the nurse-patient relation. The relevance of Edith
      Stein's concept of empathy.
AB  - This paper emanates from the concept of empathy as understood by the German
      philosopher Edith Stein. It begins by highlighting different interpretations of
      empathy. According to the German philosopher Martin Buber, empathy cannot be
      achieved as an act of will. In contrast, the psychologist Carl Rogers believes
      that empathy is identical with dialogue and is the outcome of a cognitive act of
      active listening. The empathy concept of Edith Stein, philosopher and follower of
      Edmund Husserl's phenomenology, goes beyond these conflicting views and offers a
      more complex interpretation, with relevance for both healthcare and nursing
      education. When studying Stein's three-level model of empathy, a field of tension
      between perspectives of closeness and distance becomes apparent. The paper
      concludes by suggesting Stein's model of empathy as a strategy to overcome the
      tension and meet the demands of empathy.

PMID- 16412198
TI  - The aesthetic experience of nursing.
AB  - This article highlights the distinction between the 'art of nursing' and 'fine
      art'. While something in the nature of nursing can be described as 'the art of
      nursing', it is not to be misunderstood as 'fine art' or craft. Therefore, the
      term 'aesthetic' in relation to nursing should not be linked to the aesthetic of
      modern art, but instead to a broader and more general meaning of the word. The
      paper's main focus is the aesthetic experience, which is treated in a hermeneutic
      way and elucidated from classical sources and the philosophy of nursing and from
      Art. The paper argues that the pioneers used the term 'art of nursing' in a
      metaphorical way to say something more specific on the nature of nursing. The
      term illustrates the nurse's ability to practise at the highest possible level of
      excellence.

PMID- 16412199
TI  - Wittgenstein's language games as a theory of learning disabilities.
AB  - Sociological approaches to the understanding of learning disabilities are perhaps
      not as fully developed as they might be. Wittgenstein's notion of the language
      game is elucidated, and its relevance to the analysis of learning disabilities as
      a social phenomenon is explained. This gives some insight into an alternative
      conception of what learning disabilities might be, and why people who are
      classified as having learning disabilities continue, to some extent, to be
      excluded from full participation in society.

PMID- 16412200
TI  - Towards understanding the unpresentable in nursing: some nursing philosophical
      considerations.
AB  - While nursing practice embodies certain observable and sometimes habitual
      actions, much inheres in these actions that is not immediately discernible.
      Taking on Lyotard's exegesis of the unpresentable, I undertake an analysis of the
      unpresentable as it occurs in nursing practices. The unpresentable is a place of
      alterity often excluded from dominant discourses. Yet this very alterity is what
      practising nurses face day after day. Drawing from two nursing situations, one
      from a hermeneutic phenomenological study and the other from the literature, I
      elucidate the unpresentable from a nursing point of view. Evoking Lyotard as well
      as selected philosophers from the continental philosophical tradition, I also
      question whether nursing in its present discourse is capable of responding to the
      unpresentable in nursing situations. Through the philosophical stance of
      presentation and representation, I delineate the urgent need to bring the
      otherness of the unpresentable into our nursing discourse. Nurses in practice
      confront a wide array of human differences and diversities and come to the
      realization that no framework alone can ever really have primacy over the
      multiform presentations of human suffering that so strikingly evoke alterity.

PMID- 16412201
TI  - Art as measure: nursing as safeguarding.
AB  - In this paper I explore the possibilities of nursing as safeguarding through a
      phenomenological description of a small sculpture by the German artist Kathe
      Kollwitz. My discussion will be grounded in Heidegger's understanding of
      technicity as a pervasive systematizing and aggressive challenging-out. The
      method is grounded in Merleau-Ponty's and Heidegger's contention that strong
      artworks are truth-disclosing and show up our precognitive contact with the
      world. Bringing nursing concerns to an encounter with single strong artworks can
      help us cultivate a more receptive openness to our patients.

PMID- 16412202
TI  - Critical realism as emancipatory action: the case for realistic evaluation in
      practice development.
AB  - To provide rigour when preparing a research design, the researcher needs to
      carefully consider not only the methodology but also the philosophical intent of
      the study. This, however, is often absent from reported research and provides the
      reader with little evidence by which to judge the merits of the chosen
      methodology and its influence on the study. The purpose of this paper is to set
      out the case for critical realism as a framework to guide appropriate action in
      practice development and realistic evaluation for understanding the consequences
      of those actions. It is evident that critical realism and critical social science
      share common ground. Emancipatory practice development (ePD) is based on the
      philosophy of critical social science and therefore by virtue is linked to the
      tenets of critical realism. Until now, the evaluation of ePD programme has been
      well served by 4th-generation evaluation. However, this paper outlines the need
      for a different approach to evaluation, one that is based on critical realism,
      that is concerned with emancipation, and that can be used in the ever-changing
      environment of clinical practice. Realistic evaluation not only links strongly to
      ePD programmes, but also serves as the basis for effective research questions
      that will test the outcomes of the research and inform the transferability of ePD
      mechanisms into differing contexts.

PMID- 16412203
TI  - Nussbaum's 'Capabilites Approach'.

PMID- 16412206
TI  - Primary cutaneous B-cell lymphomas: then and now.
AB  - In the past, concepts of cutaneous lymphomas were based on careful clinical and
      classical histopathological descriptions. Most primary cutaneous B-cell lymphomas
      (pCBCL) were designated as lymphosarcoma, follicular lymphoma, histiocytic
      lymphoma, reticulum-cell sarcoma or skin reticuloses. Today, pCBCL are classified
      as a fully recognized and well-defined group of extranodal lymphomas according to
      the criteria of the World Health Organization-European Organization for Research
      and Treatment of Cancer classification. Better understanding of the mechanisms of
      the pathogenesis in pCBCL will hopefully stimulate investigative research and
      provide further improvement of diagnosis and treatment.

PMID- 16412207
TI  - New aspects in the biology of cutaneous B-cell lymphomas.
AB  - Immunologic and molecular genetic studies greatly contributed to a better
      understanding and interpretation of the distinct clinico-pathologic features of
      primary cutaneous B-cell lymphomas (CBCL), which are the basis for the consensus
      WHO-EORTC classification. There is increasingly accumulating evidence that these
      well defined clinico-pathologic entities of CBCL have specific immunologic and
      molecular features, which further support their nosologic categorization as well
      as either interesting similarities with other extranodal B-cell lymphomas or
      definite peculiarities as compared to nodal B-cell lymphomas of similar histotype
      (specifically, follicle center lymphoma and diffuse large B-cell lymphoma).

PMID- 16412208
TI  - Pathobiology of CD30+ cutaneous T-cell lymphomas.
AB  - CD30+ cutaneous lymphoproliferative disorders include lymphomatoid papulosis
      (LyP) and anaplastic large cell lymphoma (ALCL). LyP is associated with
      development of lymphoma in nearly 20% of patients. Herein is reviewed the clonal
      relationship of LyP to malignant lymphoma, the concept of a common stem cell for
      LyP and associated lymphomas, and the role of genetic instability in
      lymphomagenesis. The possible role of the CD30+ cell as a regulatory T-cell is
      introduced and a model for progression of LyP to ALCL is illustrated.

PMID- 16412209
TI  - Classification of cutaneous T-cell lymphoma: from Alibert to WHO-EORTC.
AB  - Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of neoplasms
      originating from skin-homing T cells that show considerable variation in clinical
      presentation, histological appearance, immuno- phenotype, and prognosis. This
      review provides a historic overview of the classification of CTCLs from the first
      description of a patient with mycosis fungoides in 1806 to the recently published
      WHO-EORTC classification. Practical guidelines for the usage of the WHO-EORTC
      classification and relevant features of new or newly defined entities such as
      subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma,
      nasal type, primary cutaneous aggressive CD8-positive cytotoxic T-cell lymphoma,
      and cutaneous gamma/delta T-cell lymphoma are presented. The aim of this review
      is to contribute to a better communication between dermatologist and pathologist
      and in this way to a better diagnosis and classification of CTCLs.

PMID- 16412210
TI  - On the diagnosis of erythrodermic cutaneous T-cell lymphoma.
AB  - Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is the cause of less than 5% of
      all cases of generalized erythroderma. A methodical evaluation of skin, blood,
      and lymph node samples using standard histology, immunohistochemistry (IHC), flow
      cytometry (FC), and molecular analysis for evidence of a dominant T-cell clone
      has been recommended in a recently published diagnostic algorithm. In this
      commentary, the author discusses available information regarding the role of
      these diagnostic methods for the diagnosis of E-CTCL with emphasis on personal
      observations regarding skin IHC and polymerase chain reaction (PCR)-based
      molecular studies as adjunct diagnostic studies on a series of 55 patients with
      erythrodermic mycosis fungoides and 50 patients with Sezary syndrome compared to
      50 patients with extensive benign inflammatory skin disease. The conclusions are
      (1) IHC of the skin does not reliably differentiate E-CTCL from benign simulants,
      (2) presence of phenotypically abnormal T cells in the blood or expanded subsets
      of CD4+CD7- or CD4+CD26- cells by FC is particularly helpful as a diagnostic
      study, (3) the presence of an identical T-cell clone in the skin and blood also
      is a specific diagnostic criterion for E-CTCL, but exceptions may occur, and (4)
      the PCRgamma-denaturing gradient gel electrophoresis technique appears to be more
      reliable than PCRgamma-single-stranded conformational polymorphism for diagnostic
      purposes.

PMID- 16412211
TI  - Irradiation therapy: from UV light to electron beam.
AB  - Irradiation therapy represents one of the mainstay treatment modalities in
      cutaneous T-cell lymphomas. For the patch and plaque stages UV therapy is mostly
      used. Among UV light treatment broadband UVB is less effective than narrow band
      UVB. If these modalities are not sufficient, then PUVA therapy is indicated and
      might be used in even more advanced stages, including the erythrodermic stage of
      the disease. For resistant cases and remaining tumors, conventional radiotherapy
      or electron beam therapy is the treatment of a choice. If the disease is
      widespread, total skin electron beam radiation gives excellent results. One
      should not forget the possibility of combining UV therapy with radiotherapy or
      electron beam radiation, or with chemo- and immunotherapy respectively.

PMID- 16412212
TI  - Standard and new treatments in cutaneous B-cell lymphomas.
AB  - BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCL) are cutaneous non-Hodgkin
      lymphomas and can be classified clinically and by prognosis. The aim of this
      paper is to perform a review of standard and new treatments. METHOD: This paper
      provides a literature review of the different treatments of PCBCL. RESULTS:
      Surgery and radiotherapy remain the standard therapies in isolated cutaneous
      lesions. Systemic or intralesional interferon (IFN)-alpha may be an alternative
      in PCBCL with diffuse cutaneous lesions. In aggressive forms with poor prognosis,
      polychemotherapy is the first line of treatment although rituximab and
      radioimmunotherapy are evolving therapeutic options. CONCLUSION: In the majority
      of cases, the treatment of CBCL is straightforward. In aggressive forms, new
      therapies and biologic therapies may be of real interest.

PMID- 16412213
TI  - Standard and experimental therapy in cutaneous T-cell lymphomas.
AB  - Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative
      disorders, characterized by the accumulation of clonal lymphocytes in the skin.
      Skin-directed therapies are the preferred first-line modalities. There are
      interesting new developments in topical therapy using retinoids and gene-therapy
      products such as adenovirus- interferon (IFN)-gamma. Systemic treatment uses
      biologicals such as fusion molecules, monoclonal antibodies and immune response
      modifiers (IFNs and retinoids), and well-tolerated antiproliferative drugs such
      as methotrexate. Evidence-based treatment recommendation exists but is hampered
      by the lack of large multicenter randomized trials.

PMID- 16412214
TI  - CD30+ lymphoproliferative disorders: histopathology, differential diagnosis, new
      variants, and simulators.
AB  - CD30+ lymphoproliferative disorders of the skin (CD30+ LPD) represent a well
      defined spectrum of primary cutaneous T-cell lymphomas which have been recognized
      as distinct entities in recent lymphoma classifications. Lymphomatoid papulosis
      and anaplastic large-cell lymphoma share the expression of CD30 antigen as a
      common phenotypic hallmark but differ in regard to their clinical and histologic
      features as well as their biologic behavior. This article summarizes the
      histologic features of CD30+ LPD and presents recently identified new
      clinicopathologic variants of CD30+ LPD. There is an increasing number of
      reactive inflammatory disorders and neoplastic diseases which are composed of or
      contain a significant number of CD30+ cells and mimic LyP or anaplastic large
      cell lymphoma clinically or histologically. Differential diagnostic
      considerations focus on other lymphoproliferative processes with CD30+ tumor
      cells as well as non-lymphoid neoplasms and inflammatory simulators. The term
      CD30+ pseudolymphoma is proposed to designate inflammatory processes with CD30+ T
      cells. The final diagnosis of CD30+ LPD is based on a synthesis of clinical,
      histologic, phenotypic, and molecular genetic findings.

PMID- 16412215
TI  - Modulation of 5' splice site selection using tailed oligonucleotides carrying
      splicing signals.
AB  - BACKGROUND: We previously described the use of tailed oligonucleotides as a means
      of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed
      oligonucleotides that were used interfere with splicing because they contain a
      portion complementary to sequences immediately upstream of the target 5' splice
      site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP
      A1/A2 proteins. In the present study, we have tested the inhibitory activity of
      RNA oligonucleotides carrying different tail structures. RESULTS: We show that an
      oligonucleotide with a 5' tail containing the human beta-globin branch site
      sequence inhibits the use of the 5' splice site of Bcl-xL, albeit less
      efficiently than a tail containing binding sites for the hnRNP A1/A2 proteins. A
      branch site-containing tail positioned at the 3' end of the oligonucleotide also
      elicited splicing inhibition but not as efficiently as a 5' tail. The interfering
      activity of a 3' tail was improved by adding a 5' splice site sequence next to
      the branch site sequence. A 3' tail carrying a Y-shaped branch structure promoted
      similar splicing interference. The inclusion of branch site or 5' splice site
      sequences in the Y-shaped 3' tail further improved splicing inhibition.
      CONCLUSION: Our in vitro results indicate that a variety of tail architectures
      can be used to elicit splicing interference at low nanomolar concentrations,
      thereby broadening the scope and the potential impact of this antisense
      technology.

PMID- 16412216
TI  - Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals.
AB  - BACKGROUND: Lifestyle is a well-established risk factor for colorectal cancer
      (CRC) and is also found to be associated with occurrence of adenomas. In the
      present study we evaluated risk factors for both low-risk adenomas and advanced
      neoplasia in asymptomatic individuals using a single-paged questionnaire. Aiming
      to see if the questionnaire was a useful tool in picking up high-risk
      individuals. METHODS: A cross-sectional study was carried out within a randomised
      controlled colorectal cancer screening trial (n = 6961). The population comprised
      men and women born between 1946 and 1950. Before screening in year 2001 they were
      asked to fill in a questionnaire about their present lifestyle. Cases were
      categorised according to the most severe findings at screening. Analyses were
      then conducted to find risk factors associated with the presence of either low
      risk adenomas or advanced neoplasia. RESULTS: The response rate among attendees
      was 97% (3998/4111). Among these, 3447 (86%) had no neoplasia, 443 (11%) had low
      risk adenomas, and 108 (3%) had advanced neoplasia. Low-risk adenomas were
      significantly associated with current smoking, and obesity. Participants with
      advanced neoplasia had a two-fold increased risk of not adhering to any of the
      selected lifestyle recommendations compared to controls. However, current smoking
      was the only variable that reached statistical significance in the multivariate
      analysis for these lesions. A dose-response relationship to the consumption of
      cigarettes per day was shown, where OR was 2.04 (CI 1.07-3.89) for the lowest
      consumption category. CONCLUSION: The present findings indicate that a short
      questionnaire may be adequate in picking up the most consistent associations
      between lifestyle risk factors and colorectal neoplasia. Smoking and BMI were
      found to be the most significant risk factors for neoplasia, but adhering to
      recommendations on diet, and physical activity seems also to be of importance.

PMID- 16412217
TI  - Impact of epsilon and theta subunits on pharmacological properties of alpha3beta1
      GABAA receptors expressed in Xenopus oocytes.
AB  - BACKGROUND: Gamma-aminobutyric acid type A (GABAA) receptors provide the main
      inhibitory control in the brain. Their heterogeneity may make it possible to
      precisely target drug effects to selected neuronal populations. In situ
      hybridization using rat brain sections has revealed a unique expression of GABAA
      receptor epsilon and theta subunit transcripts in the locus coeruleus, where they
      are accompanied at least by alpha3, alpha2, beta1 and beta3 subunits. Here, we
      studied the pharmacology of the human alpha3beta1, alpha3beta1epsilon,
      alpha3beta1theta and alpha3beta1epsilontheta receptor subtypes expressed in
      Xenopus oocytes and compared them with the gamma2 subunit-containing receptors.
      RESULTS: The GABA sensitivites and effects of several positive modulators of
      GABAA receptors were studied in the absence and the presence of EC25 GABA using
      the two-electrode voltage-clamp method. We found 100-fold differences in GABA
      sensitivity between the receptors, alpha3beta1epsilon subtype being the most
      sensitive and alpha3beta1gamma2 the least sensitive. Also gaboxadol dose-response
      curves followed the same sensitivity rank order, with EC50 values being 72 and
      411 microM for alpha3beta1epsilon and alpha3beta1gamma2 subtypes, respectively.
      In the presence of EC25 GABA, introduction of the epsilon subunit to the receptor
      complex resulted in diminished modulatory effects by etomidate, propofol,
      pregnanolone and flurazepam, but not by pentobarbital. Furthermore, the
      alpha3beta1epsilon subtype displayed picrotoxin-sensitive spontaneous activity.
      The theta subunit-containing receptors were efficiently potentiated by the
      anesthetic etomidate, suggesting that theta subunit could bring the properties of
      beta2 or beta3 subunits to the receptor complex. CONCLUSION: The epsilon and
      theta subunits bring additional features to alpha3beta1 GABAA receptors. These
      receptor subtypes may constitute as novel drug targets in selected brain regions,
      e.g., in the brainstem locus coeruleus nuclei.

PMID- 16412219
TI  - Proteomics of early zebrafish embryos.
AB  - BACKGROUND: Zebrafish (D. rerio) has become a powerful and widely used model
      system for the analysis of vertebrate embryogenesis and organ development. While
      genetic methods are readily available in zebrafish, protocols for two dimensional
      (2D) gel electrophoresis and proteomics have yet to be developed. RESULTS: As a
      prerequisite to carry out proteomic experiments with early zebrafish embryos, we
      developed a method to efficiently remove the yolk from large batches of embryos.
      This method enabled high resolution 2D gel electrophoresis and improved Western
      blotting considerably. Here, we provide detailed protocols for proteomics in
      zebrafish from sample preparation to mass spectrometry (MS), including a
      comparison of databases for MS identification of zebrafish proteins. CONCLUSION:
      The provided protocols for proteomic analysis of early embryos enable research to
      be taken in novel directions in embryogenesis.

PMID- 16412218
TI  - Multilocus analysis of SNP and metabolic data within a given pathway.
AB  - BACKGROUND: Complex traits, which are under the influence of multiple and
      possibly interacting genes, have become a subject of new statistical
      methodological research. One of the greatest challenges facing human geneticists
      is the identification and characterization of susceptibility genes for common
      multifactorial diseases and their association to different quantitative
      phenotypic traits. RESULTS: Two types of data from the same metabolic pathway
      were used in the analysis: categorical measurements of 18 SNPs; and quantitative
      measurements of plasma levels of several steroids and their precursors. Using the
      combinatorial partitioning method we tested various thresholds for each metabolic
      trait and each individual SNP locus. One SNP in CYP19, 3UTR, two SNPs in CYP1B1
      (R48G and A119S) and one in CYP1A1 (T461N) were significantly differently
      distributed between the high and low level metabolic groups. The leave one out
      cross validation method showed that 6 SNPs in concert make 65% correct prediction
      of phenotype. Further we used pattern recognition, computing the p-value by Monte
      Carlo simulation to identify sets of SNPs and physiological characteristics such
      as age and weight that contribute to a given metabolic level. Since the SNPs
      detected by both methods reside either in the same gene (CYP1B1) or in 3
      different genes in immediate vicinity on chromosome 15 (CYP19, CYP11 and CYP1A1)
      we investigated the possibility that they form intragenic and intergenic
      haplotypes, which may jointly account for a higher activity in the pathway. We
      identified such haplotypes associated with metabolic levels. CONCLUSION: The
      methods reported here may enable to study multiple low-penetrance genetic factors
      that together determine various quantitative phenotypic traits. Our preliminary
      data suggest that several genes coding for proteins involved in a common pathway,
      that happen to be located on common chromosomal areas and may form intragenic
      haplotypes, together account for a higher activity of the whole pathway.

PMID- 16412220
TI  - OpWise: operons aid the identification of differentially expressed genes in
      bacterial microarray experiments.
AB  - BACKGROUND: Differentially expressed genes are typically identified by analyzing
      the variation between replicate measurements. These procedures implicitly assume
      that there are no systematic errors in the data even though several sources of
      systematic error are known. RESULTS: OpWise estimates the amount of systematic
      error in bacterial microarray data by assuming that genes in the same operon have
      matching expression patterns. OpWise then performs a Bayesian analysis of a
      linear model to estimate significance. In simulations, OpWise corrects for
      systematic error and is robust to deviations from its assumptions. In several
      bacterial data sets, significant amounts of systematic error are present, and
      replicate-based approaches overstate the confidence of the changers dramatically,
      while OpWise does not. Finally, OpWise can identify additional changers by
      assigning genes higher confidence if they are consistent with other genes in the
      same operon. CONCLUSION: Although microarray data can contain large amounts of
      systematic error, operons provide an external standard and allow for reasonable
      estimates of significance. OpWise is available at
      http://microbesonline.org/OpWise.

PMID- 16412221
TI  - Competition between the DNA unwinding and strand pairing activities of the Werner
      and Bloom syndrome proteins.
AB  - BACKGROUND: The premature aging and cancer-prone Werner and Bloom syndromes are
      caused by defects in the RecQ helicase enzymes WRN and BLM, respectively.
      Recently, both WRN and BLM (as well as several other RecQ members) have been
      shown to possess a strand annealing activity in addition to the requisite DNA
      unwinding activity. Since an annealing function would appear to directly oppose
      the action of a helicase, we have examined in this study the dynamic equilibrium
      between unwinding and annealing mediated by either WRN or BLM. RESULTS: Our
      investigation into the competition between annealing and unwinding demonstrates
      that, under standard reaction conditions, WRN- or BLM-mediated annealing can
      partially or completely mask unwinding as measured in standard helicase assays.
      Several strategies were employed to suppress the annealing activity so that the
      actual strength of WRN- or BLM-dependent unwinding could be more accurately
      assessed. Interestingly, if a DNA oligomer complementary to one strand of the DNA
      substrate to be unwound is added during the helicase reaction, both WRN and BLM
      unwinding is enhanced, presumably by preventing protein-mediated re-annealing.
      This strategy allowed measurement of WRN-catalyzed unwinding of long (80 base
      pair) duplex regions and fully complementary, blunt-ended duplexes, both of which
      were otherwise quite refractory to the helicase activity of WRN. Similarly, the
      addition of trap strand stimulated the ability of BLM to unwind long and blunt
      ended duplexes. The stimulatory effect of the human replication protein A (hRPA,
      the eukaryotic single-stranded DNA binding protein) on both WRN- and BLM
      dependent unwinding was also re-examined in light of its possible role in
      preventing re-annealing. Our results show that hRPA influences the outcome of WRN
      and BLM helicase assays by both inhibiting re-annealing and directly promoting
      unwinding, with the larger contribution from the latter mechanism. CONCLUSION:
      These findings indicate that measurements of unwinding by WRN, BLM, and probably
      other RecQ helicases are complicated by their annealing properties. Thus, WRN-
      and BLM-dependent unwinding activities are significantly stronger than previously
      believed. Since this broadens the range of potential physiological substrates for
      WRN and BLM, our findings have relevance for understanding their functions in
      vitro and in vivo.

PMID- 16412222
TI  - A molecular epidemiological study of rabies epizootics in kudu (Tragelaphus
      strepsiceros) in Namibia.
AB  - BACKGROUND: A panel of 37 rabies virus isolates were collected and studied,
      originating mainly from the northern and central regions of Namibia, between 1980
      and 2003. RESULTS: These virus isolates demonstrated a high degree of genetic
      similarity with respect to a 400 bp region of the nucleoprotein gene, with the
      virus isolates originating from kudu antelope (n = 10) sharing 97.2-100%
      similarity with jackal isolates, and 97-100% similarity with those isolated from
      domestic dogs. Phylogenetic analysis suggested that these viruses were all of the
      canid rabies biotype of southern Africa. The viruses from kudu were closely
      associated with jackal isolates (n = 6), bat-eared fox isolates (n = 2) and
      domestic dog isolates (n = 2) at the genetic level and identical at the amino
      acid level, irrespective of the year of isolation. CONCLUSION: These data suggest
      that jackal and kudu may form part of the same epidemiological cycle of rabies in
      Namibian wildlife, and might demonstrate the close-relationship between rabies
      virus strains that circulate within Namibia and those that circulate between
      Namibia and its neighbouring countries such as Botswana and South Africa.

PMID- 16412223
TI  - Hemoptysis, a developing world perspective.
AB  - BACKGROUND: Hemoptysis is a significant clinical presentation in respiratory
      medicine. Often a life threatening emergency, it mandates prompt assessment and
      intervention. Various investigations and management protocols are proposed
      globally, to advocate a standardized approach towards patients presenting with
      hemoptysis. It is the etiology, however, that has been known to influence
      clinical outcome and prognosis. With marked contrast in geographical patterns of
      pulmonary pathologies, etiological agents for hemoptysis vary over the world.
      Studies in West, usually demonstrate neoplastic and non-granulomatous causes to
      be the leading agents for hemoptysis. The diagnostic accuracy of various
      investigations and efficacy of management alternatives has been established
      there. Developing nations differ in their burden of diseases of lung. Lack of
      health resources and initiative often prevent quality research in critical areas.
      DESIGN: This is a retrospective observational study with a cross-sectional design
      in which charts of all patients admitted with the presentation of haemoptysis in
      the past ten years will be reviewed, at Aga Khan University Hospital, Karachi,
      Pakistan. A series of variables, based on previous literature on haemoptysis
      related to the objectives of present study, will be determined in the study.
      Demographics, co-morbids and etiology will be determined. Findings of various
      investigation modalities and their accuracy in localizing the bleeding site will
      be determined. Efficacy of different management strategies will also be observed.
      Also observed will be any complications and follow-up. DISCUSSION: Pakistan is a
      third world nation of over 150 million, established as highly endemic for
      pulmonary tuberculosis. To date no study has been generated to look into
      hemoptysis patterns, in this nation. Lack of evidence based medicine poses a
      major hindrance towards confident decision-making in the approach towards a
      patient presenting with hemoptysis in this country. This study is devised to
      obtain the first insight in this direction, from this part of the world. The
      etiologies, accuracy of various investigations and efficacy of treatment options
      will be investigated. The results and conclusions will prove to be of value not
      just for health administrators in this country, but many other regions that share
      similarities in patterns of pulmonary pathologies.

PMID- 16412224
TI  - Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines
      in patients with cardiovascular disease.
AB  - INTRODUCTION: Inflammation contributes to cardiovascular disease and is
      exacerbated with increased adiposity, particularly omental adiposity; however,
      the role of epicardial fat is poorly understood. METHODS: For these studies the
      expression of inflammatory markers was assessed in epicardial fat biopsies from
      coronary artery bypass grafting (CABG) patients using quantitative RT-PCR.
      Further, the effects of chronic medications, including statins, as well as peri
      operative glucose, insulin and potassium infusion, on gene expression were also
      assessed. Circulating resistin, CRP, adiponectin and leptin levels were
      determined to assess inflammation. RESULTS: The expression of adiponectin,
      resistin and other adipocytokine mRNAs were comparable to that in omental fat.
      Epicardial CD45 expression was significantly higher than control depots (p <
      0.01) indicating significant infiltration of macrophages. Statin treated patients
      showed significantly lower epicardial expression of IL-6 mRNA, in comparison with
      the control abdominal depots (p < 0.001). The serum profile of CABG patients
      showed significantly higher levels of both CRP (control: 1.28 +/- 1.57 microg/mL
      vs CABG: 9.11 +/- 15.7 microg/mL; p < 0.001) and resistin (control: 10.53 +/-
      0.81 ng/mL vs CABG: 16.8 +/- 1.69 ng/mL; p < 0.01) and significantly lower levels
      of adiponectin (control: 29.1 +/- 14.8 microg/mL vs CABG: 11.9 +/- 6.0 microg/mL;
      p < 0.05) when compared to BMI matched controls. CONCLUSION: Epicardial and
      omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise
      in part from macrophage infiltration into the epicardial fat. This study
      highlights that chronic inflammation occurs locally as well as systemically
      potentially contributing further to the pathogenesis of coronary artery disease.

PMID- 16412226
TI  - Biochemical and morphological changes in endothelial cells in response to hypoxic
      interstitial edema.
AB  - BACKGROUND: A correlation between interstial pulmonary matrix disorganization and
      lung cellular response was recently documented in cardiogenic interstitial edema
      as changes in the signal-cellular transduction platforms (lipid microdomains:
      caveoale and lipid rafts). These findings led to hypothesize a specific "sensing"
      function by lung cells resulting from a perturbation in cell-matrix interaction.
      We reason that the cell-matrix interaction may differ between the cardiogenic and
      the hypoxic type of lung edema due to the observed difference in the sequential
      degradation of matrix proteoglycans (PGs) family. In cardiogenic edema a major
      fragmentation of high molecular weight PGs of the interfibrillar matrix was
      found, while in hypoxia the fragmentation process mostly involved the PGs of the
      basement membrane controlling microvascular permeability. Based on these
      considerations, we aim to describe potential differences in the lung cellular
      response to the two types of edema. METHODS: We analysed the composition of
      plasma membrane and of lipid microdomains in lung tissue samples from
      anesthetized rabbits exposed to mild hypoxia (12 % O2 for 3-5 h) causing
      interstitial lung edema. Lipid analysis was performed by chromatographic
      techniques, while protein analysis by electrophoresis and Western blotting. Lipid
      peroxidation was assessed on total plasma membranes by a colorimetric assay
      (Bioxytech LPO-586, OxisResearch). Plasma membrane fluidity was also assessed by
      fluorescence. Lipid microdomains were isolated by discontinuous sucrose gradient.
      We also performed a morphometric analysis on lung cell shape on TEM images from
      lung tissue specimen. RESULTS: After hypoxia, phospholipids content in plasma
      membranes remained unchanged while the cholesterol/phospholipids ratio increased
      significantly by about 9% causing a decrease in membrane fluidity. No significant
      increase in lipid peroxidation was detected. Analysis of lipid microdomains
      showed a decrease of caveolin-1 and AQP1 (markers of caveolae), and an increase
      in CD55 (marker of lipid rafts). Morphometry showed a significant decrease in
      endothelial cell volume, a marked increase in the cell surface/volume ratio and a
      decrease in caveolar density; epithelial cells did not show morphological
      changes. CONCLUSION: The biochemical, signaling and morphological changes
      observed in lung endothelial cell exposed to hypoxia are opposite to those
      previously described in cardiogenic edema, suggesting a differential cellular
      response to either type of edema.

PMID- 16412225
TI  - RTE and CTE mRNA export elements synergistically increase expression of unstable,
      Rev-dependent HIV and SIV mRNAs.
AB  - Studies of retroviral mRNA export identified two distinct RNA export elements
      utilizing conserved eukaryotic mRNA export mechanism(s), namely the Constitutive
      Transport Element (CTE) and the RNA Transport Element (RTE). Although RTE and CTE
      are potent in nucleocytoplasmic mRNA transport and expression, neither element is
      as powerful as the Rev-RRE posttranscriptional control. Here, we found that
      whereas CTE and the up-regulatory mutant RTEm26 alone increase expression from a
      subgenomic gag and env clones, the combination of these elements led to a several
      hundred-fold, synergistic increase. The use of the RTEm26-CTE combination is a
      simple way to increase expression of poorly expressed retroviral genes to levels
      otherwise only achieved via more cumbersome RNA optimization. The potent RTEm26
      CTE element could be useful in lentiviral gene therapy vectors, DNA-based vaccine
      vectors, and gene transfer studies of other poorly expressed genes.

PMID- 16412227
TI  - In vitro modulation of inflammatory cytokine and IgG levels by extracts of Perna
      canaliculus.
AB  - BACKGROUND: Inflammation is a predominant characteristic of autoimmune diseases
      which is characterized by the increased expression of pro-inflammatory cytokines.
      Soon to be published work from our laboratory has shown that ingestion of Perna
      canaliculus prevents the development of autoimmune diseases such as Systemic
      Lupus Erythematosus and rheumatoid arthritis in laboratory animals. The current
      paper attempts to illustrate how Perna can alleviate inflammation by modulating
      inflammatory cytokines, cyclooxygenase enzymes and Immunoglobulin-G (IgG) levels.
      METHODS: In the present study, hydrochloric acid [HCl] and Tween-20 were used to
      develop extracts of Perna. These extracts were assayed for protein content.
      Increasing concentrations of these extracts were then tested in cell culture for
      modulation of inflammatory cytokine, cyclooxygenase enzymes and IgG levels.
      Parallel tests were run using an available glycogen extract of Perna as a
      comparison to our in-house laboratory preparations. RESULTS: Tween-20 Perna
      extracts were found to be more stable and less toxic in cell culture than HCl
      digest of Perna. They also assayed higher in protein content that HCl extracts.
      Although both extracts inhibited IgG production in V2E9 hybridomas, Tween-20
      extracts were more consistent in IgG suppression than HCl extracts. Overall Tween
      20 extracts effectively decreased levels of TNF-alpha, IL-1, IL-2 and IL-6 as
      observed using cytokine bioassays. Twenty micrograms of Tween-20 Perna extracts
      induced such significant decreases in inflammatory cytokine production that when
      tested on sensitive cell lines, they very nearly abolished the decrease in
      viability induced by these cytokines. Tween-20 extracts effectively inhibited
      both COX-1 and COX-2 cyclooxygenase activity. As a comparison, the glycogen
      extract also demonstrated a similar though weaker effect on COX-1 and COX-2
      enzymes. The active components of both extracts (Tween-20 and glycogen) were
      observed to possess molecular weights above 100 kDa. Although the anti-cytokine
      activity of the Tween-20 extract was destroyed by Proteinase-K treatment, the
      anti-COX-1 and anti-COX-2 activity of both the extracts were not sensitive to
      protease treatment. CONCLUSION: We have successfully demonstrated modulation in
      the levels of inflammatory cytokines, cyclooxygenase enzymes and immunoglobulins
      by our in-house laboratory preparations of Perna canaliculus, whereby suggesting
      an immunomodulatory role of Perna canaliculus in regulating inflammation.

PMID- 16412228
TI  - An outbreak of post-acupuncture cutaneous infection due to Mycobacterium
      abscessus.
AB  - BACKGROUND: Despite the increasing popularity of acupuncture, the importance of
      infection control is not adequately emphasized in Oriental medicine. In December
      2001, an Oriental medical doctor in Seoul, South Korea, encountered several
      patients with persistent, culture-negative skin lesions on the trunk and
      extremities at the sites of prior acupuncture treatment. We identified and
      investigated an outbreak of Mycobacterium abscessus cutaneous infection among the
      patients who attended this Oriental medicine clinic. METHODS: Patients were
      defined as clinic patients with persistent cutaneous infections at the
      acupuncture sites. Medical records for the previous 7 months were reviewed.
      Clinical specimens were obtained from the patients and an environmental
      investigation was performed. M. abscessus isolates, cultured from patients, were
      compared by pulsed-field gel electrophoresis (PFGE). RESULTS: Forty patients who
      attended the Oriental medicine clinic and experienced persistent cutaneous wound
      infections were identified. Cultures from five of these patients proved positive,
      and all other diagnoses were based on clinical and histopathologic examinations.
      All environmental objects tested were negative for M. abscessus, however, most
      were contaminated by various nosocomial pathogens. Molecular analysis using PFGE
      found all wound isolates to be identical. CONCLUSION: We have identified a large
      outbreak of rapidly growing mycobacterial infection among patients who received
      acupuncture at a single Oriental medicine clinic. Physicians should suspect
      mycobacterial infections in patients with persistent cutaneous infections
      following acupuncture, and infection control education including hygienic
      practice, should be emphasized for Oriental medical doctors practicing
      acupuncture.

PMID- 16412229
TI  - How international is bioethics? A quantitative retrospective study.
AB  - BACKGROUND: Studying the contribution of individual countries to leading journals
      in a specific discipline can highlight which countries have the most impact on
      that discipline and whether a geographic bias exists. This article aims to
      examine the international distribution of publications in the field of bioethics.
      METHODS: Retrospective quantitative study of nine peer reviewed journals in the
      field of bioethics and medical ethics (Bioethics, Cambridge Quarterly of
      Healthcare Ethics, Hastings Center Report, Journal of Clinical Ethics, Journal of
      Medical Ethics, Kennedy Institute of Ethics Journal, Nursing Ethics, Christian
      Bioethics, and Theoretical Medicine and Bioethics). RESULTS: In total, 4,029
      articles published between 1990 and 2003 were retrieved from the nine bioethical
      journals under study. The United States (59.3%, n = 2390), the United Kingdom
      (13.5%, n = 544), Canada (4%, n = 160) and Australia (3.8%, n = 154) had the
      highest number of publications in terms of absolute number of publications. When
      normalized to population size, smaller affluent countries, such as New Zealand,
      Finland and Sweden were more productive than the United States. The number of
      studies originating from the USA was decreasing in the period between 1990 and
      2003. CONCLUSION: While a lot of peer reviewed journals in the field of bioethics
      profile themselves as international journals, they certainly do not live up to
      what one would expect from an "international" journal. The fact that English
      speaking countries, and to a larger extent American authors, dominate the
      international journals in the field of bioethics is a clear geographic bias
      towards the bioethical discussions that are going on in these journals.

PMID- 16412230
TI  - Factor VII deficiency and developmental abnormalities in a patient with partial
      monosomy of 13q and trisomy of 16p: case report and review of the literature.
AB  - BACKGROUND: Unbalanced chromosomal translocations may present with a variety of
      clinical and laboratory findings and provide insight into the functions of genes
      on the involved chromosomal segments. CASE PRESENTATION: A 9 year-old boy
      presented to our clinic with Factor VII deficiency, microcephaly, a seizure
      disorder, multiple midline abnormalities (agenesis of the corpus callosum,
      imperforate anus, bilateral optic nerve hypoplasia), developmental delay,
      hypopigmented macules, short 5th fingers, and sleep apnea due to enlarged
      tonsils. Cytogenetic and fluorescence in situ hybridization analyses revealed an
      unbalanced translocation involving the segment distal to 16p13 replacing the
      segment distal to 13q33 [46, XY, der(13)t(13;16)(q33;p13.3)]. Specific BAC-probes
      were used to confirm the extent of the 13q deletion. CONCLUSION: This unique
      unbalanced chromosomal translocation may provide insights into genes important in
      midline development and underscores the previously-reported phenotype of Factor
      VII deficiency in 13q deletions.

PMID- 16412231
TI  - Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell
      carcinomas of the oral cavity.
AB  - BACKGROUND: Intermediary filaments are involved in cell motility and cancer
      progression. In a variety of organs, the expression of distinct intermediary
      filaments are associated with patient prognosis. In this study, we seeked to
      define the prognostic potential of cytokeratin and vimentin expression patterns
      in squamous cell carcinomas (SCC's) of the oral cavity. METHODS: 308 patients
      with histologically proven and surgically treated squamous cell carcinomas of the
      oral cavity were investigated for the immunohistochemical expression of a variety
      of intermediary filaments including high- and low-molecular weight cytokeratins
      (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using
      the tissue microarray technique. Correlations between clinical features and the
      expression of Cytokeratins and vimentin were evaluated statistically by Kaplan
      Meier curves and multivariate Cox regression analysis. RESULTS: The expression of
      Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical
      prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be
      reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in
      multivariate-analysis. No significant correlation with patient prognosis could be
      found for the expression of the other cytokeratins and for vimentin. CONCLUSION:
      The expression of Ck 8/18 in SCC's of the oral cavity is an independent
      prognostic marker and indicates a decreased overall and progression free
      survival. These results provide an extended knowledge about the role of
      intermediary filament expression patterns in SCC's.

PMID- 16412232
TI  - Sequential boundaries approach in clinical trials with unequal allocation ratios.
AB  - BACKGROUND: In clinical trials, both unequal randomization design and sequential
      analyses have ethical and economic advantages. In the single-stage-design (SSD),
      however, if the sample size is not adjusted based on unequal randomization, the
      power of the trial will decrease, whereas with sequential analysis the power will
      always remain constant. Our aim was to compare sequential boundaries approach
      with the SSD when the allocation ratio (R) was not equal. METHODS: We evaluated
      the influence of R, the ratio of the patients in experimental group to the
      standard group, on the statistical properties of two-sided tests, including the
      two-sided single triangular test (TT), double triangular test (DTT) and SSD by
      multiple simulations. The average sample size numbers (ASNs) and power (1-beta)
      were evaluated for all tests. RESULTS: Our simulation study showed that choosing
      R = 2 instead of R = 1 increases the sample size of SSD by 12% and the ASN of the
      TT and DTT by the same proportion. Moreover, when R = 2, compared to the adjusted
      SSD, using the TT or DTT allows to retrieve the well known reductions of ASN
      observed when R = 1, compared to SSD. In addition, when R = 2, compared to SSD,
      using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1,
      but maintains the power of the test to its planned value. CONCLUSION: This study
      indicates that when the allocation ratio is not equal among the treatment groups,
      sequential analysis could indeed serve as a compromise between ethicists,
      economists and statisticians.

PMID- 16412233
TI  - Analysis of the interaction of extracellular matrix and phenotype of bladder
      cancer cells.
AB  - BACKGROUND: The extracellular matrix has a major effect upon the malignant
      properties of bladder cancer cells both in vitro in 3-dimensional culture and in
      vivo. Comparing gene expression of several bladder cancer cells lines grown under
      permissive and suppressive conditions in 3-dimensional growth on cancer-derived
      and normal-derived basement membrane gels respectively and on plastic in
      conventional tissue culture provides a model system for investigating the
      interaction of malignancy and extracellular matrix. Understanding how the
      extracellular matrix affects the phenotype of bladder cancer cells may provide
      important clues to identify new markers or targets for therapy. METHODS: Five
      bladder cancer cell lines and one immortalized, but non-tumorigenic, urothelial
      line were grown on Matrigel, a cancer-derived ECM, on SISgel, a normal-derived
      ECM, and on plastic, where the only ECM is derived from the cells themselves. The
      transcriptomes were analyzed on an array of 1186 well-annotated cancer derived
      cDNAs containing most of the major pathways for malignancy. Hypervariable genes
      expressing more variability across cell lines than a set expressing technical
      variability were analyzed further. Expression values were clustered, and to
      identify genes most likely to represent biological factors, statistically over
      represented ontologies and transcriptional regulatory elements were identified.
      RESULTS: Approximately 400 of the 1186 total genes were expressed 2 SD above
      background. Approximately 100 genes were hypervariable in cells grown on each
      ECM, but the pattern was different in each case. A core of 20 were identified as
      hypervariable under all 3 growth conditions, and 33 were hypervariable on both
      SISgel and Matrigel, but not on plastic. Clustering of the hypervariable genes
      showed very different patterns for the same 6 cell types on the different ECM.
      Even when loss of cell cycle regulation was identified, different genes were
      involved, depending on the ECM. Under the most permissive conditions of growth
      where the malignant phenotype was fully expressed, activation of AKT was noted.
      TGFbeta1 signaling played a major role in the response of bladder cancer cells to
      ECM. Identification of TREs on genes that clustered together suggested some
      clustering was driven by specific transcription factors. CONCLUSION: The
      extracellular matrix on which cancer cells are grown has a major effect on gene
      expression. A core of 20 malignancy-related genes were not affected by matrix,
      and 33 were differentially expressed on 3-dimensional culture as opposed to
      plastic. Other than these genes, the patterns of expression were very different
      in cells grown on SISgel than on Matrigel or even plastic, supporting the
      hypothesis that growth of bladder cancer cells on normal matrix suppresses some
      malignant functions. Unique underlying regulatory networks were driving gene
      expression and could be identified by the approach outlined here.

PMID- 16412234
TI  - Fanconi anemia manifesting as a squamous cell carcinoma of the hard palate: a
      case report.
AB  - Fanconi anemia is a rare autosomal recessive disorder characterized by various
      congenital malformations, progressive bone marrow failure at a very young age and
      of solid tumors development. The authors present a rare case of a squamous cell
      carcinoma of the hard palate in a Fanconi Anaemia patient. The atypical clinical
      manifestation rendered the diagnosis more difficult. This case, for age of
      appearance, sex and localization, is unique in international literature. We
      recommend a quarterly follow up of the oral-rhino-pharynx complex in FA patients
      and to consider as carcinomas, all oral lesions that last more than two weeks.

PMID- 16412235
TI  - Spontaneous regression of bone metastasis from renal cell carcinoma; a case
      report.
AB  - BACKGROUND: Spontaneous regression of metastatic renal cell carcinoma is rarely
      observed. CASE PRESENTATION: Metastatic renal cell carcinoma was identified in a
      70-year-old male using computed tomography-guided percutaneous needle biopsy. Two
      months after the diagnosis, a partial resection of the sternal bone was
      performed. Pathological examination revealed granulated tissue with bleeding and
      necrosis but no carcinogenic cells. CONCLUSION: We report a pathologically
      identified case in which a sternal bone metastasis that was noticed two years
      after radical nephrectomy regressed completely and spontaneously.

PMID- 16412236
TI  - Reduced hippocampal activation during episodic encoding in middle-aged
      individuals at genetic risk of Alzheimer's disease: a cross-sectional study.
AB  - BACKGROUND: The presence of the apolipoprotein E (APOE) epsilon4 allele is a
      major risk factor for the development of Alzheimer's disease (AD), and has been
      associated with metabolic brain changes several years before the onset of typical
      AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been
      used to demonstrate hippocampal activation during measurement of episodic
      encoding, but the effect of the epsilon4 allele on hippocampal activation has not
      been firmly established. METHODS: The present study examined the effects of APOE
      genotype on brain activation patterns in the medial temporal lobe (MTL) during an
      episodic encoding task using a well-characterized novel item versus familiar item
      contrast in cognitively normal, middle-aged (mean = 54 years) individuals who had
      at least one parent with AD. RESULTS: We found that epsilon3/4 heterozygotes
      displayed reduced activation in the hippocampus and MTL compared to epsilon3/3
      homozygotes. There were no significant differences between the groups in age,
      education or neuropsychological functioning, suggesting that the altered brain
      activation seen in epsilon3/4 heterozygotes was not associated with impaired
      cognitive function. We also found that participants' ability to encode
      information on a neuropsychological measure of learning was associated with
      greater activation in the anterior MTL in the epsilon3/3 homozygotes, but not in
      the epsilon3/4 heterozygotes. CONCLUSION: Together with previous studies
      reporting reduced glucose metabolism and AD-related neuropathology, this study
      provides convergent validity for the idea that the MTL exhibits functional
      decline associated with the APOE epsilon4 allele. Importantly, these changes were
      detected in the absence of meaningful neuropsychological differences between the
      groups. A focus of ongoing work in this laboratory is to determine if these
      findings are predictive of subsequent cognitive decline.

PMID- 16412237
TI  - High sensitivity assays for docetaxel and paclitaxel in plasma using solid-phase
      extraction and high-performance liquid chromatography with UV detection.
AB  - BACKGROUND: The taxanes paclitaxel and docetaxel have traditionally been used in
      high doses every third week in the treatment of cancer. Lately there has been a
      trend towards giving weekly low doses to improve the therapeutic index. This
      article describes the development of high performance liquid chromatographic
      (HPLC) methods suitable for monitoring taxane levels in patients, focusing on
      patients receiving low-dose therapy. METHODS: Paclitaxel and docetaxel were
      extracted from human plasma by solid phase extraction, and detected by absorbance
      at 227 nm after separation by reversed phase high performance liquid
      chromatography. The methods were validated and their performance were tested
      using samples from patients receiving paclitaxel or docetaxel. RESULTS: The
      limits of quantitation were 1 nM for docetaxel and 1.2 nM for paclitaxel. For
      both compounds linearity was confirmed from the limit of quantitation up to 1000
      nM in plasma. The recoveries ranged between 92% and 118% for docetaxel and
      between 76% and 104% for paclitaxel. Accuracy and precision were within
      international acceptance criteria, that is within +/- 15%, except at the limit of
      quantitation where values within +/- 20% are acceptable. Low-dose patients
      included in an on going clinical trial had a median docetaxel concentration of
      2.8 nM at 72 hours post infusion. Patients receiving 100 mg/m2 of paclitaxel had
      a mean paclitaxel concentration of 21 nM 48 hours after the end of infusion.
      CONCLUSION: We have developed an HPLC method using UV detection capable of
      quantifying 1 nM of docetaxel in plasma samples. The method should be useful for
      pharmacokinetic determinations at all relevant doses of docetaxel. Using a
      similar methodology paclitaxel can be quantified down to a concentration of 1.2
      nM in plasma with acceptable accuracy and precision. We further demonstrate that
      the previously reported negative influence of Cremophor EL on assay performance
      may be overcome by degradation of the detergent by incubation with lipase.

PMID- 16412238
TI  - Peroxisomal proliferator activated receptor-gamma deficiency in a Canadian
      kindred with familial partial lipodystrophy type 3 (FPLD3).
AB  - BACKGROUND: Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian
      Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG
      encoding peroxisomal proliferator-activated receptor-gamma. Both dominant
      negative and haploinsufficiency mechanisms have been suggested for this
      condition. METHODS: We present a Canadian FPLD3 kindred with an affected mother
      who had loss of fat on arms and legs, but no increase in facial, neck,
      suprascapular or abdominal fat. She had profound insulin resistance, diabetes,
      severe hypertriglyceridemia and relapsing pancreatitis, while her pre-pubescent
      daughter had normal fat distribution but elevated plasma triglycerides and C
      peptide and depressed high-density lipoprotein cholesterol. RESULTS: The mother
      and daughter were each heterozygous for PPARG nonsense mutation Y355X, whose
      protein product in vitro was transcriptionally inactive with no dominant-negative
      activity against the wild-type receptor. In addition the mutant protein appeared
      to be markedly unstable. CONCLUSION: Taken together with previous studies of
      human PPARG mutations, these findings suggest that PPAR-gamma deficiency due
      either to haploinsufficiency or to substantial activity loss due to dominant
      negative interference of the normal allele product's function can each contribute
      to the FPLD3 phenotype.

PMID- 16412239
TI  - Influence of advanced age of maternal grandmothers on Down syndrome.
AB  - BACKGROUND: Down syndrome (DS) is the most common chromosomal anomaly associated
      with mental retardation. This is due to the occurrence of free trisomy 21 (92
      95%), mosaic trisomy 21 (2-4%) and translocation (3-4%). Advanced maternal age is
      a well documented risk factor for maternal meiotic nondisjunction. In India three
      children with DS are born every hour and more DS children are given birth to by
      young age mothers than by advanced age mothers. Therefore, detailed analysis of
      the families with DS is needed to find out other possible causative factors for
      nondisjunction. METHODS: We investigated 69 families of cytogenetically confirmed
      DS children and constructed pedigrees of these families. We also studied 200
      randomly selected families belonging to different religions as controls.
      Statistical analysis was carried out using logistic regression. RESULTS: Out of
      the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy
      21 and there were none with translocation. The number of DS births was greater
      for the young age mothers compared with the advanced age mothers. It has also
      been recorded that young age mothers (18 to 29 years) born to their mothers at
      the age 30 years and above produced as high as 91.3% of children with DS. The
      logistic regression of case- control study of DS children revealed that the odds
      ratio of age of grandmother was significant when all the four variables were used
      once at a time. However, the effect of age of mother and father was smaller than
      the effect of age of maternal grandmother. Therefore, for every year of
      advancement of age of the maternal grandmother, the risk (odds) of birth of DS
      baby increases by 30%. CONCLUSION: Besides the known risk factors, mother's age,
      father's age, the age of the maternal grandmother at the time of birth of the
      mother is a risk factor for the occurrence of Down syndrome.

PMID- 16412240
TI  - Prediction of protein structural class with Rough Sets.
AB  - BACKGROUND: A new method for the prediction of protein structural classes is
      constructed based on Rough Sets algorithm, which is a rule-based data mining
      method. Amino acid compositions and 8 physicochemical properties data are used as
      conditional attributes for the construction of decision system. After reducing
      the decision system, decision rules are generated, which can be used to classify
      new objects. RESULTS: In this study, self-consistency and jackknife tests on the
      datasets constructed by G.P. Zhou (Journal of Protein Chemistry, 1998, 17: 729
      738) are used to verify the performance of this method, and are compared with
      some of prior works. The results showed that the rough sets approach is very
      promising and may play a complementary role to the existing powerful approaches,
      such as the component-coupled, neural network, SVM, and LogitBoost approaches.
      CONCLUSION: The results with high success rates indicate that the rough sets
      approach as proposed in this paper might hold a high potential to become a useful
      tool in bioinformatics.

PMID- 16412241
TI  - Knowledge loss of medical students on first year basic science courses at the
      University of Saskatchewan.
AB  - BACKGROUND: Many senior undergraduate students from the University of
      Saskatchewan indicated informally that they did not remember much from their
      first year courses and wondered why we were teaching content that did not seem
      relevant to later clinical work or studies. To determine the extent of the
      problem a course evaluation study that measured the knowledge loss of medical
      students on selected first year courses was conducted. This study replicates
      previous memory decrement studies with three first year medicine basic science
      courses, something that was not found in the literature. It was expected that
      some courses would show more and some courses would show less knowledge loss.
      METHODS: In the spring of 2004 over 20 students were recruited to retake
      questions from three first year courses: Immunology, physiology, and
      neuroanatomy. Student scores on the selected questions at the time of the final
      examination in May 2003 (the 'test') were compared with their scores on the
      questions 10 or 11 months later (the 're-test') using paired samples t -tests. A
      repeated-measures MANOVA was used to compare the test and re-test scores among
      the three courses. The re-test scores were matched with the overall student
      ratings of the courses and the student scores on the May 2003 examinations.
      RESULTS: A statistically significant main effect of knowledge loss (F = 297.385;
      p < .001) and an interaction effect by course (F = 46.081; p < .001) were found.
      The students' scores in the Immunology course dropped 13.1%, 46.5% in
      Neuroanatomy, and 16.1% in physiology. Bonferroni post hoc comparisons showed a
      significant difference between Neuroanatomy and Physiology (mean difference of
      10.7, p = .004). CONCLUSION: There was considerable knowledge loss among medical
      students in the three basic science courses tested and this loss was not uniform
      across courses. Knowledge loss does not seem to be related to the marks on the
      final examination or the assessment of course quality by the students.

PMID- 16412243
TI  - Developments in Australian general practice 2000-2002: what did these contribute
      to a well functioning and comprehensive Primary Health Care System?
AB  - BACKGROUND: In recent years, national and state/territory governments have
      undertaken an increasing number of initiatives to strengthen general practice and
      improve its links with the rest of the primary health care sector. This paper
      reviews how far these initiatives were contributing to a well functioning and
      comprehensive primary health care system during the period 2000-2002, using a
      normative model of primary health care and data from a descriptive study to
      evaluate progress. RESULTS: There was a significant number of programs, at both
      state/territory and national level. Most focused on individual care, particularly
      for chronic disease, rather than population health approaches. There was little
      evidence of integration across programs: each tended to be based in and focus on
      a single jurisdiction, and build capacity chiefly within the services funded
      through that jurisdiction. As a result, the overall effect was patchy, with
      similar difficulties being noted across all jurisdictions and little gain in
      overall system capacity for effective primary health care. CONCLUSION: Efforts to
      develop more effective primary health care need a more balanced approach to
      reform, with a better balance across the different elements of primary health
      care and greater integration across programs and jurisdictions. One way ahead is
      to form a single funding agency, as in the UK and New Zealand, and so remove the
      need to work across jurisdictions and manage their competing interests. A second,
      perhaps less politically challenging starting point, is to create an agreed
      framework for primary health care within which a collective vision for primary
      health care can be developed, based on population health needs, and the
      responsibilities of different sectors services can be negotiated. Either of these
      approaches would be assisted by a more systematic and comprehensive program of
      research and evaluation for primary health care.

PMID- 16412242
TI  - Overcoming inherent problems of preference-based techniques for measuring health
      benefits: an empirical study in the context of kidney transplantation.
AB  - BACKGROUND: Economic valuations of health care programs often require using
      patients as subjects, implying that research methodology should conform to the
      surrounding social, cultural and ethical context. The significance of patients'
      opinions in health care decisions has been well defined but in Greece, and
      perhaps elsewhere, clinicians remain skeptical. The purpose of this study was to
      investigate, for the first time in Greece, the feasibility of measuring
      preference-based health-state utilities and willingness to pay and to determine
      the context-based adaptations required to overcome inherent elicitation problems.
      METHODS: A survey including a time trade-off (TTO), a standard gamble (SG), and
      two willingness-to-pay (WTP) questions was self-administered to a homogenous
      group of 606 end stage renal disease patients in 24 dialysis facilities
      throughout Greece and the overall response rate was 78.5%. Typical elicitation
      methods were adapted to overcome methodological problems such as subjective life
      expectancy and question framing. Spearman's correlation coefficients were
      calculated between utilities and WTP and parametric tests (independent samples t
      test and ANOVA) examined score differences as a result of demographic and
      clinical factors. RESULTS: Mean health-state utilities were 72.56 (TTO) and 91.06
      (SG) and these were statistically significantly different (P < 0.0005).
      Significant correlations, in the expected directions, were observed between TTO -
      SG, TTO - WTP and SG - WTP (P < 0.01). High ceiling effects were observed in the
      TTO and SG methods indicating patients' adversity to risk and unwillingness to
      trade-off life years. Higher WTP was observed from younger patients (P < 0.0005),
      males (P < 0.05), higher education levels (P < 0.01), single (P < 0.0005) and
      employed (P < 0.005). CONCLUSION: This study demonstrated, to a fair extent, that
      adapting research methods to context-based particularities does not necessarily
      compromise results and should be considered in situations where standard methods
      cannot be applied. On the other hand, it is emphasized that the results from this
      study are preliminary and should be interpreted cautiously until further research
      demonstrates the practicality, reliability and validity of alternative
      measurement approaches.

PMID- 16412245
TI  - Topographic determinants of foot and mouth disease transmission in the UK 2001
      epidemic.
AB  - BACKGROUND: A key challenge for modelling infectious disease dynamics is to
      understand the spatial spread of infection in real landscapes. This ideally
      requires a parallel record of spatial epidemic spread and a detailed map of
      susceptible host density along with relevant transport links and geographical
      features. RESULTS: Here we analyse the most detailed such data to date arising
      from the UK 2001 foot and mouth epidemic. We show that Euclidean distance between
      infectious and susceptible premises is a better predictor of transmission risk
      than shortest and quickest routes via road, except where major geographical
      features intervene. CONCLUSION: Thus, a simple spatial transmission kernel based
      on Euclidean distance suffices in most regions, probably reflecting the
      multiplicity of transmission routes during the epidemic.

PMID- 16412244
TI  - Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron
      specific dominant negative mitogen activated protein kinase kinase (MEK).
AB  - BACKGROUND: Numerous studies have implicated spinal extracellular signal
      regulated kinases (ERKs) as mediators of nociceptive plasticity. These studies
      have utilized pharmacological inhibition of MEK to demonstrate a role for ERK
      signaling in pain, but this approach cannot distinguish between effects of ERK in
      neuronal and non-neuronal cells. The present studies were undertaken to test the
      specific role of neuronal ERK in formalin-induced inflammatory pain. Dominant
      negative MEK (DN MEK) mutant mice in which MEK function is suppressed exclusively
      in neurons were tested in the formalin model of inflammatory pain. RESULTS:
      Formalin-induced second phase spontaneous pain behaviors as well as thermal
      hyperalgesia measured 1 - 3 hours post-formalin were significantly reduced in the
      DN MEK mice when compared to their wild type littermate controls. In addition,
      spinal ERK phosphorylation following formalin injection was significantly reduced
      in the DN MEK mice. This was not due to a reduction of the number of unmyelinated
      fibers in the periphery, since these were almost double the number observed in
      wild type controls. Further examination of the effects of suppression of MEK
      function on a downstream target of ERK phosphorylation, the A-type potassium
      channel, showed that the ERK-dependent modulation of the A-type currents is
      significantly reduced in neurons from DN MEK mice compared to littermate wild
      type controls. CONCLUSION: Our results demonstrate that the neuronal MEK-ERK
      pathway is indeed an important intracellular cascade that is associated with
      formalin-induced inflammatory pain and thermal hyperalgesia.

PMID- 16412246
TI  - Spatial analysis of campylobacter infection in the Canadian province of Manitoba.
AB  - BACKGROUND: The study describes population level variations in campylobacter
      incidence within the Canadian province of Manitoba, and the relationship to
      sociodemographic and landscape related characteristics. Using data derived from
      the Manitoba Health Public Health Branch communicable disease surveillance
      database, the study applied a number of spatial and ecological techniques to
      visualize, explore and model campylobacter incidence for the years 1996 to 2004.
      Analytical techniques used in the study included spatial smoothing, the spatial
      scan statistic, the Gini coefficient, and Poisson regression analysis. RESULTS:
      The study demonstrated marked and statistically significant geographic
      variability in the rates of campylobacter incidence in Manitoba.. The incidence
      of campylobacter was observed to be significantly higher in populations living in
      rural and agricultural areas of the province, with the highest rates occurring in
      populations living in proximity to high densities of farm animals (cows, pigs,
      chickens). The study also observed that the age specific pattern of campylobacter
      incidence in rural Manitoba was very different than the urban pattern, with the
      incidence rate in the 0-4 year age group seven times higher in rural Manitoba
      than in the City of Winnipeg. CONCLUSION: The study demonstrates the value of a
      deploying a diverse set of spatial techniques to better understand the dynamics
      of an enteric disease such as campylobacter infection. The study concludes that
      there may be three distinct mechanisms for the transmission of campylobacter in
      Manitoba which are operating simultaneously. These include broad population
      exposure to a centralized food system endemically infected with the campylobacter
      organism, exposure to local level factors such as farm animals or contaminated
      water, and exposure to campylobacter infection through foreign travel.

PMID- 16412248
TI  - Pore forming polyalkylpyridinium salts from marine sponges versus synthetic
      lipofection systems: distinct tools for intracellular delivery of cDNA and siRNA.
AB  - BACKGROUND: Haplosclerid marine sponges produce pore forming polyalkylpyridinium
      salts (poly-APS), which can be used to deliver macromolecules into cells. The aim
      of this study was to investigate the delivery of DNA, siRNA and lucifer yellow
      into cells mediated by poly-APS and its potential mechanisms as compared with
      other lipofection systems (lipofectamine and N4,N9-dioleoylspermine (LipoGen)).
      DNA condensation was evaluated and HEK 293 and HtTA HeLa cells were used to
      investigate pore formation and intracellular delivery of cDNA, siRNA and lucifer
      yellow. RESULTS: Poly-APS and LipoGen were both found to be highly efficient DNA
      condensing agents. Fura-2 calcium imaging was used to measure calcium transients
      indicative of cell membrane pore forming activity. Calcium transients were evoked
      by poly-APS but not LipoGen and lipofectamine. The increases in intracellular
      calcium produced by poly-APS showed temperature sensitivity with greater
      responses being observed at 12 degrees C compared to 21 degrees C. Similarly,
      delivery of lucifer yellow into cells with poly-APS was enhanced at lower
      temperatures. Transfection with cDNA encoding for the expression enhanced green
      fluorescent protein was also evaluated at 12 degrees C with poly-APS,
      lipofectamine and LipoGen. Intracellular delivery of siRNA was achieved with
      knockdown in beta-actin expression when lipofectamine and LipoGen were used as
      transfection reagents. However, intracellular delivery of siRNA was not achieved
      with poly-APS. CONCLUSION: Poly-APS mediated pore formation is critical to its
      activity as a transfection reagent, but lipofection systems utilise distinct
      mechanisms to enable delivery of DNA and siRNA into cells.

PMID- 16412249
TI  - Case report of 5 siblings: malnutrition? Rickets? DiGeorge syndrome?
      Developmental delay?
AB  - BACKGROUND: Parents of six children are facing a trial on charges of aggravated
      manslaughter in the care a 5 1/2 month old infant who died suddenly and neglect
      of their four older children for causing them to be malnourished by feeding them
      all an exclusively raw foods vegan diet. Both parents declined plea bargains and
      plan to defend themselves in court. CASE PRESENTATION: The fifth child born to a
      married couple was breast-fed until 2 1/2 months. Subsequently, the parents fed
      the baby an exclusively raw foods diet prepared in a blender at home. The four
      older children, ages 18 months-6 1/2 years also ate an exclusively raw foods
      vegan diet. None of the four older children had significant previous injuries or
      serious illnesses. At autopsy, the infant weighed 3180 mg (6.99 pounds) and
      appeared emaciated. The thymus gland was absent and parathyroid glands were not
      located. The lungs were "congested." DiGeorge anomaly cannot be ruled out from
      these findings. Although, the coroner ruled that "malnutrition" was the sole
      cause of death, malnutrition, according to the World Health Organization
      definition, cannot be diagnosed in this infant. Compared with standard growth
      charts, the older children fell 2.1-4.1 standard deviations below the mean for
      North American children in height and weight. Labs were normal except for a low
      cholesterol level in all and a low prealbumin in one of three children tested.
      Therefore, malnutrition cannot be diagnosed in these children. The pediatrician
      diagnosed rickets in the four-year-old. However, chest x-rays were normal in all
      and long bone x-rays showed minimal changes in one child--no sign of rickets. The
      clinical diagnosis of rickets was not confirmed by the Center for Disease
      Control's criteria. A psychologist diagnosed the 18-month-old as developmentally
      delayed to the level of a 15-month-old, but this diagnosis is questionable.
      CONCLUSION: The raw foods vegan diet and possibly inherited small stature from
      the father's side account for their relatively low heights and weights. Catch-up
      growth will probably occur on the standard American diet but would have also been
      expected if they had remained on a vegan diet.

PMID- 16412247
TI  - Latency: the hidden HIV-1 challenge.
AB  - Eradication of HIV-1 from an infected individual cannot be achieved by current
      regimens. Viral reservoirs established early during the infection remain
      unaffected by anti-retroviral therapy for a long time and are able to replenish
      systemic infection upon interruption of the treatment. Therapeutic targeting of
      viral latency will require a better understanding of the basic mechanisms
      underlying the establishment and long-term maintenance of HIV-1 in resting memory
      CD4 T cells, the most prominent reservoir of transcriptionally silent provirus.
      Since the molecular mechanisms that permit long term transcriptional control of
      proviral gene expression in these cells are still obscure, this review aims at
      summarizing the various aspects of the problem that need to be considered. In
      particular, this review will focus the attention on the control of transcription
      imposed by chromatin through various epigenetic mechanisms. Exploring the
      molecular details of viral latency will provide new insights for eventual future
      therapeutics that aim at viral eradication.

PMID- 16412250
TI  - The Epc-N domain: a predicted protein-protein interaction domain found in select
      chromatin associated proteins.
AB  - BACKGROUND: An underlying tenet of the epigenetic code hypothesis is the
      existence of protein domains that can recognize various chromatin structures. To
      date, two major candidates have emerged: (i) the bromodomain, which can recognize
      certain acetylation marks and (ii) the chromodomain, which can recognize certain
      methylation marks. RESULTS: The Epc-N (Enhancer of Polycomb-N-terminus) domain is
      formally defined herein. This domain is conserved across eukaryotes and is
      predicted to form a right-handed orthogonal four-helix bundle with extended
      strands at both termini. The types of amino acid residues that define the Epc-N
      domain suggest a role in mediating protein-protein interactions, possibly
      specifically in the context of chromatin binding, and the types of proteins in
      which it is found (known components of histone acetyltransferase complexes)
      strongly suggest a role in epigenetic structure formation and/or recognition.
      There appear to be two major Epc-N protein families that can be divided into four
      unique protein subfamilies. Two of these subfamilies (I and II) may be related to
      one another in that subfamily I can be viewed as a plant-specific expansion of
      subfamily II. The other two subfamilies (III and IV) appear to be related to one
      another by duplication events in a primordial fungal-metazoan-mycetozoan
      ancestor. Subfamilies III and IV are further defined by the presence of an
      evolutionarily conserved five-center-zinc-binding motif in the loop connecting
      the second and third helices of the four-helix bundle. This motif appears to
      consist of a PHD followed by a mononuclear Zn knuckle, followed by a PHD-like
      derivative, and will thus be referred to as the PZPM. All non-Epc-N proteins
      studied thus far that contain the PZPM have been implicated in histone
      methylation and/or gene silencing. In addition, an unusual phyletic distribution
      of Epc-N-containing proteins is observed. CONCLUSION: The data suggest that the
      Epc-N domain is a protein-protein interaction module found in chromatin
      associated proteins. It is possible that the Epc-N domain serves as a direct link
      between histone acetylation and methylation statuses. The unusual phyletic
      distribution of Epc-N-containing proteins may provide a conduit for future
      insight into how different organisms form, perceive and respond to epigenetic
      information.

PMID- 16412251
TI  - A blended knowledge translation initiative to improve colorectal cancer staging
      [ISRCTN56824239].
AB  - BACKGROUND: A significant gap has been documented between best practice and the
      actual practice of surgery. Our group identified that colorectal cancer staging
      in Ontario was suboptimal and subsequently developed a knowledge translation
      strategy using the principles of social marketing and the influence of expert and
      local opinion leaders for colorectal cancer. METHODS/DESIGN: Opinion leaders were
      identified using the Hiss methodology. Hospitals in Ontario were cluster
      randomized to one of two intervention arms. Both groups were exposed to a formal
      continuing medical education session given by the expert opinion leader for
      colorectal cancer. In the treatment group the local Opinion Leader for colorectal
      cancer was detailed by the expert opinion leader for colorectal cancer and
      received a toolkit. Forty-two centres agreed to have the expert opinion leader
      for colorectal cancer come and give a formal continuing medical education session
      that lasted between 50 minutes and 4 hours. No centres refused the intervention.
      These sessions were generally well attended by most surgeons, pathologists and
      other health care professionals at each centre. In addition all but one of the
      local opinion leaders for colorectal cancer met with the expert opinion leader
      for colorectal cancer for the academic detailing session that lasted between 15
      and 30 minutes. DISCUSSION: We have enacted a unique study that has attempted to
      induce practice change among surgeons and pathologists using an adapted social
      marketing model that utilized the influence of both expert and local opinion
      leaders for colorectal cancer in a large geographic area with diverse practice
      settings.

PMID- 16412252
TI  - Hypoxia-inducible factor-1alpha polymorphisms and TSC1/2 mutations are
      complementary in head and neck cancers.
AB  - BACKGROUND: Polymorphisms or mutations in hypoxia inducible factor-1 alpha (HIF
      1alpha) that increases its activity and stability under normoxia have recently
      been identified. Likewise, disruption of the TSC1/TSC2 complex through loss of
      TSC1 or TSC2 has been shown to result in abnormal accumulation of HIF-1alpha.
      Here, we investigate the novel polymorphisms in exon 12, that approximate the
      oxygen-dependent degradation domain of HIF-1alpha in five cell lines and 28
      patients with oral squamous carcinomas. Moreover, we assess for the presence of
      polymorphisms and mutations in TSC1 and TSC2, to ascertain if dysregulation of
      such might complement HIF-1alpha expression. RESULTS: Denaturing high pressure
      liquid chromatography (DHPLC) analysis on PCR fragments in exon 12 of HIF-1alpha
      from 28 patients with OSCC revealed that 6 of 28 patients had mismatched
      heteroduplex patterns. Genomic DNA was extracted from peripheral blood leukocytes
      and direct sequencing showed that in 5 of the six cases these changes represented
      polymorphisms while, one case was a somatic mutation. Analyses of TSC1 and TSC2
      revealed heteroduplexes in exons: TSC1 exon 17; TSC2 exons 36, 40, and 41. The
      relative levels of HIF-1alpha were significantly greater for tumors possessing a
      HIF-1alpha polymorphism or mutation within exon 12, whereas tumors possessing a
      deletion or polymorphism in TSC1/TSC2 displayed a trend for higher levels of HIF
      1alpha. Western blot analyses for HIF-1alpha, TSC1 and TSC2 in five SCC cell
      lines revealed high levels of HIF-1alpha in SCC cells possessing TSC1 and/or TSC2
      mutations. Wild-type TSC2 cells targeted with siRNA to TSC2 exhibited increased
      levels of HIF-1alpha. Transfection of a HIF-1alpha mutant produced higher levels
      of HIF-1alpha in TSC1/TSC2 mutant cell lines than in wild type cells. TSC1/TSC2
      mutant cell lines administered Rapamycin blocked S6 phorphorylation and
      diminished the levels of HIF-1alpha to those observed in cell lines with wild
      type TSC1/TSC2. CONCLUSION: Dysregulation of the TSC1/TSC2 complex by mutation
      compliments HIF-1alpha polymorphisms in the expression of HIF-1alpha in SCC of
      the head and neck, and may provide biomarkers to predict responses to specific
      therapies and overall disease prognosis.

PMID- 16412253
TI  - Analysis of a marine phototrophic biofilm by confocal laser scanning microscopy
      using the new image quantification software PHLIP.
AB  - BACKGROUND: Confocal laser scanning microscopy (CLSM) is the method of choice to
      study interfacial biofilms and acquires time-resolved three-dimensional data of
      the biofilm structure. CLSM can be used in a multi-channel modus where the
      different channels map individual biofilm components. This communication presents
      a novel image quantification tool, PHLIP, for the quantitative analysis of large
      amounts of multichannel CLSM data in an automated way. PHLIP can be freely
      downloaded from http://phlip.sourceforge.net. RESULTS: PHLIP is an open source
      public license Matlab toolbox that includes functions for CLSM imaging data
      handling and ten image analysis operations describing various aspects of biofilm
      morphology. The use of PHLIP is here demonstrated by a study of the development
      of a natural marine phototrophic biofilm. It is shown how the examination of the
      individual biofilm components using the multi-channel capability of PHLIP allowed
      the description of the dynamic spatial and temporal separation of diatoms,
      bacteria and organic and inorganic matter during the shift from a bacteria
      dominated to a diatom-dominated phototrophic biofilm. Reflection images and
      weight measurements complementing the PHLIP analyses suggest that a large part of
      the biofilm mass consisted of inorganic mineral material. CONCLUSION: The
      presented case study reveals new insight into the temporal development of a
      phototrophic biofilm where multi-channel imaging allowed to parallel monitor the
      dynamics of the individual biofilm components over time. This application of
      PHLIP presents the power of biofilm image analysis by multi-channel CLSM software
      and demonstrates the importance of PHLIP for the scientific community as a
      flexible and extendable image analysis platform for automated image processing.

PMID- 16412254
TI  - Genomic analysis of a 1 Mb region near the telomere of Hessian fly chromosome X2
      and avirulence gene vH13.
AB  - BACKGROUND: To have an insight into the Mayetiola destructor (Hessian fly)
      genome, we performed an in silico comparative genomic analysis utilizing genetic
      mapping, genomic sequence and EST sequence data along with data available from
      public databases. RESULTS: Chromosome walking and FISH were utilized to identify
      a contig of 50 BAC clones near the telomere of the short arm of Hessian fly
      chromosome X2 and near the avirulence gene vH13. These clones enabled us to
      correlate physical and genetic distance in this region of the Hessian fly genome.
      Sequence data from these BAC ends encompassing a 760 kb region, and a fully
      sequenced and assembled 42.6 kb BAC clone, was utilized to perform a comparative
      genomic study. In silico gene prediction combined with BLAST analyses was used to
      determine putative orthology to the sequenced dipteran genomes of the fruit fly,
      Drosophila melanogaster, and the malaria mosquito, Anopheles gambiae, and to
      infer evolutionary relationships. CONCLUSION: This initial effort enables us to
      advance our understanding of the structure, composition and evolution of the
      genome of this important agricultural pest and is an invaluable tool for a whole
      genome sequencing effort.

PMID- 16412255
TI  - The association between diabetes related medical costs and glycemic control: a
      retrospective analysis.
AB  - BACKGROUND: The objective of this research is to quantify the association between
      direct medical costs attributable to type 2 diabetes and level of glycemic
      control. METHODS: A longitudinal analysis using a large health plan
      administrative database was performed. The index date was defined as the first
      date of diabetes diagnosis and individuals had to have at least two HbA1c values
      post index date in order to be included in the analyses. A total of 10,780
      individuals were included in the analyses. Individuals were stratified into
      groups of good (N = 6,069), fair (N = 3,586), and poor (N = 1,125) glycemic
      control based upon mean HbA1c values across the study period. Differences between
      HbA1c groups were analyzed using a generalized linear model (GLM), with
      differences between groups tested by utilizing z-statistics. The analyses allowed
      a wide range of factors to affect costs. RESULTS: 42.1% of those treated only
      with oral agents, 66.1% of those treated with oral agents and insulin, and 57.2%
      of those treated with insulin alone were found to have suboptimal control
      (defined as fair or poor) throughout the study period (average duration of follow
      up was 2.95 years). Results show that direct medical costs attributable to type 2
      diabetes were 16% lower for individuals with good glycemic control than for those
      with fair control ($1,505 vs. $1,801, p < 0.05), and 20% lower for those with
      good glycemic control than for those with poor control ($1,505 vs. $1,871, p <
      0.05). Prescription drug costs were also significantly lower for individuals with
      good glycemic control compared to those with fair ($377 vs. $465, p < 0.05) or
      poor control ($377 vs. $423, p < 0.05). CONCLUSION: Almost half (44%) of all
      patients diagnosed with type 2 diabetes are at sub-optimal glycemic control.
      Evidence from this analysis indicates that the direct medical costs of treating
      type 2 diabetes are significantly higher for individuals who have fair or poor
      glycemic control than for those who have good glycemic control. Patients under
      fair control account for a greater proportion of the cost burden associated with
      antidiabetic prescription drugs.

PMID- 16412256
TI  - Sex differences in the rate of fatigue development and recovery.
AB  - BACKGROUND: Many musculoskeletal injuries in the workplace have been attributed
      to the repetitive loading of muscle and soft tissues. It is not disputed that
      muscular fatigue is a risk factor for musculoskeletal injury, however the
      disparity between gender with respect to muscular fatigability and rate of
      recovery is not well understood. Current health and safety guidelines do not
      account for sex differences in fatiguability and may be predisposing one gender
      to greater risk. The purpose of this study was to quantify the sex differences in
      fatigue development and recovery rate of lower and upper body musculature after
      repeated bouts of sustained isometric contractions. METHODS: Twenty-seven healthy
      males (n = 12) and females (n = 15) underwent bilateral localized fatigue of
      either the knee extensors (male: n = 8; female: n = 8), elbow flexors (male: n =
      8; female: n = 10), or both muscle groups. The fatigue protocol consisted of ten
      30-second sub-maximal isometric contractions. The changes in maximum voluntary
      contraction (MVC), electrically evoked twitches, and motor unit activation (MUA)
      were assessed along with the ability to control the sustained contractions (SLP)
      during the fatigue protocol using a mixed four-factor repeated measures ANOVA
      (gender x side x muscle x time) design with significance set at p < 0.05.
      RESULTS: There was a significant loss of MVC, MUA, and evoked twitch amplitude
      from pre- to post-fatigue in both the arms and legs. Males had greater relative
      loss of isometric force, a higher rate of fatigue development, and were less
      capable of maintaining the fatiguing contractions in the legs when compared to
      the females. CONCLUSION: The nature of the induced fatigue was a combination of
      central and peripheral fatigue that did not fully recover over a 45-minute
      period. The results appear to reflect sex differences that are peripheral, and
      partially support the muscle mass hypothesis for explaining differences in
      muscular fatigue.

PMID- 16412258
TI  - Testing the niche apportionment hypothesis with parasite communities: is random
      assortment always the rule?
AB  - Niche apportionment models have only been applied once to parasite communities.
      Only the random assortment model (RA), which indicates that species abundances
      are independent from each other and that interspecific competition is
      unimportant, provided a good fit to 3 out of 6 parasite communities investigated.
      The generality of this result needs to be validated, however. In this study we
      apply 5 niche apportionment models to the parasite communities of 14 fish species
      from the Great Barrier Reef. We determined which model fitted the data when using
      either numerical abundance or biomass as an estimate of parasite abundance, and
      whether the fit of niche apportionment models depends on how the parasite
      community is defined (e.g. ecto, endoparasites or all parasites considered
      together). The RA model provided a good fit for the whole community of parasites
      in 7 fish species when using biovolume (as a surrogate of biomass) as a measure
      of species abundance. The RA model also fitted observed data when ecto- and
      endoparasites were considered separately, using abundance or biovolume, but less
      frequently. Variation in fish sizes among species was not associated with the
      probability of a model fitting the data. Total numerical abundance and biovolume
      of parasites were not related across host species, suggesting that they capture
      different aspects of abundance. Biovolume is not only a better measurement to use
      with niche-orientated models, it should also be the preferred descriptor to
      analyse parasite community structure in other contexts. Most of the biological
      assumptions behind the RA model, i.e. randomness in apportioning niche space,
      lack of interspecific competition, independence of abundance among different
      species, and species with variable niches in changeable environments, are in
      accordance with some previous findings on parasite communities. Thus, parasite
      communities may generally be unsaturated with species, with empty niches, and
      interspecific interactions may generally be unimportant in determining parasite
      community structure.

PMID- 16412257
TI  - Detection and identification of Lactobacillus delbrueckii subsp. lactis
      bacteriophages by PCR.
AB  - A sensitive PCR method amplifying an internal fragment of the major tail protein
      gene was developed to detect Lactobacillus delbrueckii subsp. lactis lytic
      bacteriophages in undefined, thermophilic whey starters used in Italy for
      production of Grana and Provolone cheeses. PCR was applied to several lytic Lb.
      delbrueckii subsp. lactis bacteriophages, which were highly diverse according to
      restriction analysis and phage host range. PCR detected the presence of phages in
      two out of 11 cultures, when applied to whey starters for Grana Padano cheese
      sampled from different cheese plants. The presence of actively growing phages in
      infected cultures was confirmed by traditional test. The PCR method proved to be
      useful to screen for the presence of Lb. delbrueckii subsp. lactis phages in
      thermophilic whey starters.

PMID- 16412259
TI  - Establishment of a mouse macula densa cell line with an nNOS promoter driving
      EGFP expression.
AB  - We describe a unique method for establishing a functionally intact macula densa
      cell line from immortalized renal cells in culture. The macula densa is involved
      in the tubuloglomerular feedback (TGF) system in the kidney and specifically
      expresses neuronal nitric oxide synthase (nNOS). A 347 bp portion of the nNOS
      promoter was used to drive the expression of enhanced green fluorescence protein
      (EGFP). An immortalized distal tubule (DT) cell line was derived from distal
      tubules microdissected from the kidneys of SV40 large T antigen transgenic mice.
      Immunofluorescence labeling using an antibody against nNOS revealed no specific
      EGFP expression in immunofluorescence-negative DT cells. The established cell
      line (NE-MD) showed a time-dependent increase in signals of the nNOS protein when
      they were incubated with 12 microM furosemide (an inhibitor of Na(+)-K(+)-2Cl(-)
      symporter) for 5 h. In conclusion, this newly developed macula densa cell line
      will be useful in studies of the TGF stem.

PMID- 16412260
TI  - Beneficial effects of melatonin in experimental models of Alzheimer disease.
AB  - Alzheimer's disease (AD), a progressive degenerative disorder, is characterized
      by the presence of amyloid deposits, neurofibrillary tangles and neuron loss.
      Emerging evidence indicates that antioxidants could be useful either for the
      prevention or treatment of AD. It has been shown that melatonin is a potent
      antioxidant and free radical scavenger. Additionally, melatonin stimulates
      several antioxidative enzymes and improves mitochondrial energy metabolism. These
      findings led us to study amyloid precursor protein transgenic mice,
      ovariectomized rats, and pheochromocytoma and astroglioma cell lines, to observe
      whether melatonin had any effect on Alzheimer's symptoms or pathological changes.
      We found that melatonin had many beneficial effects in experimental models of AD,
      including improvement of cognitive function, anti-oxidative injury, anti
      apoptosis, inhibition of beta-amyloid (Abeta) deposition and Abeta fiber
      formation. Several groups have shown that melatonin has an inhibitory effect on
      tau protein hyperphosphorylation. These actions may potentially slow down or stop
      the progression of dementia.

PMID- 16412261
TI  - Recent trends in drug abuse in China.
AB  - Drug abuse has spread quickly since reemerging as a national problem in China in
      the late 1980s. The number of registered drug abusers increased from 70,000 in
      1990 to more than one million by the end of 2004. In addition to opioids, abuse
      of 'new' types of drugs including 3,4-methylenedioxymethamphetamine (MDMA) and
      ketamine has spread since 1997. Illicit drug trafficking and production have
      swept most of southern China, and throughout the country drug abuse has caused
      many problems for both abusers and the community. One major drug-related problem
      is the spread of HIV, which has caused major social and economic damage in China.
      In response, the Chinese government has begun an anti-drug campaign, including
      legislative measures to control drug abuse. However, changing the public's
      attitudes toward drug abusers and breaking the link between drug use and HIV
      spread are equally important.

PMID- 16412262
TI  - Neuroprotective effects of stearic acid against toxicity of oxygen/glucose
      deprivation or glutamate on rat cortical or hippocampal slices.
AB  - AIM: To observe the effects of stearic acid, a long-chain saturated fatty acid
      consisting of 18 carbon atoms, on brain (cortical or hippocampal) slices insulted
      by oxygen-glucose deprivation (OGD), glutamate or sodium azide (NaN3) in vitro.
      METHODS: The activities of hippocampal slices were monitored by population spikes
      recorded in the CA1 region. In vitro injury models of brain slice were induced by
      10 min of OGD, 1 mmol/L glutamate or 10 mmol/L NaN3. After 30 min of pre
      incubation with stearic acid (3-30 micromol/L), brain slices (cortical or
      hippocampal) were subjected to OGD, glutamate or NaN3, and the tissue activities
      were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. MK886 [5
      mmol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR
      alpha)] or BADGE (bisphenol A diglycidyl ether; 100 micromol/L; an antagonist of
      PPAR-gamma) were tested for their effects on the neuroprotection afforded by
      stearic acid. RESULTS: Viability of brain slices was not changed significantly
      after direct incubation with stearic acid. OGD, glutamate and NaN3 injury
      significantly decreased the viability of brain slices. Stearic acid (3-30
      micromol/L) dose-dependently protected brain slices from OGD and glutamate injury
      but not from NaN3 injury, and its neuroprotective effect was completely abolished
      by BADGE. CONCLUSION: Stearic acid can protect brain slices (cortical or
      hippocampal) against injury induced by OGD or glutamate. Its neuroprotective
      effect may be mainly mediated by the activation of PPAR-gamma.

PMID- 16412263
TI  - High density lipoprotein 3 inhibits oxidized low density lipoprotein-induced
      apoptosis via promoting cholesterol efflux in RAW264.7 cells.
AB  - AIM: To investigate the protective effect of high density lipoprotein 3 (HDL3) on
      oxidized low density lipoprotein (ox-LDL)-induced apoptosis in RAW264.7 cells.
      METHODS: RAW264.7 cells were exposed to 50 mg/L ox-LDL for various durations up
      to 48 h, and apoptosis was detected using Hoechst 33258 staining and flow
      cytometric analysis. Total cholesterol levels were detected by high performance
      liquid chromatography, cholesterol efflux was determined by Tritium labeling, and
      the cellular lipid droplets were assayed by oil red O staining. RESULTS:
      Treatment with 50 mg/L ox-LDL for 12, 24, and 48 h increased the apoptotic rate
      of RAW264.7 cells in a time-dependent manner. The peak apoptotic rate (47.7%) was
      observed after 48 h incubation. HDL3 at various concentrations (50 mg/L, 100
      mg/L, and 200 mg/L) inhibited the ox-LDL (50 mg/L for 48 h)-mediated apoptosis
      that was accompanied by an increased rate of intracellular cholesterol efflux,
      and decreased total cholesterol levels in cells in a concentration-dependent
      manner. Blockage of cholesterol efflux by brefeldin decreased the protective
      effect of HDL3 on ox-LDL-induced apoptosis. Increase of the cholesterol efflux
      effected by another cholesterol acceptor,beta-cyclodextrin, led to a dramatic
      decrease in the apoptotic rate of cells. CONCLUSION: HDL3 antagonizes ox-LDL
      induced apoptosis in RAW264.7 cells, through reducing the accumulation of toxic
      cholesterol.

PMID- 16412264
TI  - Role of norepinephrine in development of short-term myocardial hibernation.
AB  - AIM: To investigate the role of norepinephrine in the development of short-term
      myocardial hibernation. METHODS: Hearts were removed from rats and set up as
      isometrically beating or short-term hibernation models. The hearts were perfused
      with modified Krebs-Henseleit buffer under a controlled perfusion pressure. The
      myocardial ultrastructure was examined, and the content of ATP, phosphocreatine,
      and glycogen in myocardium, the extent of myocyte apoptosis, and the amount of
      Bcl-2 and Bax products were determined after 120-min ischemia assessed by TUNEL
      and immunocytochemistry. RESULTS: There was no significant difference between the
      reserpinized hearts and the NS control group with respect to heart function,
      myocardial ultrastructure, ATP, phosphocreatine, or glycogen content, myocyte
      apoptosis, or amount of Bax or Bcl-2 products. However, relative to the normal
      saline group, in the norepinephrine-treated hearts, heart function, and
      myocardial ultrastructure deteriorated significantly, apoptosis and amount of Bax
      product increased significantly, and the ATP, phosphocreatine, and glycogen
      content decreased significantly, as did the amount of Bcl-2 product. CONCLUSION:
      Myocardial norepinephrine does not contribute to the development of short-term
      hibernation, but that exogenous NE can induce progressive decreases in coronary
      flow and cardiac performance, which might result from the increases in apoptosis
      and necrosis. Norepinephrine may be an important factor in the deterioration of
      myocardial structure and function during hibernation, and that anti-adrenergic
      treatment may be helpful for the development and sustainment of short-term
      myocardial hibernation.

PMID- 16412265
TI  - Ouabain at pathological concentrations might induce damage in human vascular
      endothelial cells.
AB  - AIM: To examine the time- and dose-dependent effects of ouabain on human
      umbilical vein endothelial cells (HUVEC) in vivo, and the changes in aortic
      endothelium and the different expression levels of Kv4.2 in vitro. METHODS: The
      proliferation of HUVEC and cell death were determined by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the incorporation of
      [3H]TdR, trypan blue staining, and lactate dehydrogenase (LDH) release. The
      response of endothelial cells to ouabain was explored with a complementary DNA
      microarray and a candidate gene was found. Ouabain-sensitive hypertensive rats
      were established by chronic administration of ouabain. Changes in the aortic
      endothelium were observed by electron microscopy, and the expression level of
      Kv4.2 in different animals was studied by using real-time quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Ouabain stimulated the
      proliferation of HUVEC at physiological concentrations (0.3-0.9 nmol/L). Ouabain
      at pathological concentrations (0.9-1.8 nmol/L) inhibited proliferation and
      induced cell death. mRNA profile analysis indicated that 340 genes were
      differentially expressed after ouabain treatment: 145 were upregulated, of which
      6 were upregulated significantly, including KCND2 (encoding the potassium voltage
      gated channel shal-related subfamily member 2). The upregulated genes were mainly
      related to cell metabolism and transcription. In ouabain-sensitive hypertensive
      rats, the aortic endothelium was damaged and Kv4.2 (coded by KCND2) was over
      expressed. CONCLUSION: The physiological role of ouabain in HUVEC might involve
      the control of growth and metabolism. Ouabain at pathological concentrations
      might affect the structure and function of the vascular endothelium by
      modification of expression of the KCND2 gene, and participate vascular remodeling
      in hypertension.

PMID- 16412266
TI  - Effects of neutral sulfate berberine on LPS-induced cardiomyocyte TNF-alpha
      secretion, abnormal calcium cycling, and cardiac dysfunction in rats.
AB  - AIM: To evaluate the effect of neutral sulfate berberine on cardiac function,
      tumor necrosis factor alpha (TNF-alpha) release, and intracellular calcium
      concentration ([Ca(2+)]i) in cardiomyocytes exposed to lipopolysaccharide (LPS).
      METHODS: Primary cultured rat cardiomyocytes were prepared from ventricles of 3-4
      day old Sprague-Dawley rats. TNF-alpha concentrations in cell-conditioned media
      were measured by using a Quantikine enzyme-linked immunosorbent assay kit, and
      cardiomyocyte [Ca(2+)]i was measured by using Fura-2/AM. The isolated rat hearts
      were perfused in the Langendorff mode. RESULTS: LPS at doses of 1, 5, 10, and 20
      microg/mL markedly stimulated TNF-alpha secretion from cardiomyocytes, and
      neutral sulfate berberine inhibited LPS-induced TNF-alpha production.
      Intracellular calcium concentration was significantly decreased after LPS
      stimulation for 1 h, and increased 2 h after LPS treatment. Pretreatment with
      neutral sulfate berberine reversed the LPS-induced [Ca(2+)]i alterations,
      although neutral sulfate berberine did not inhibit a rapid increase in
      cardiomyocyte [Ca(2+)]i induced by LPS. Perfusion of isolated hearts with LPS
      (100 microg/mL) for 20 min resulted in significantly impaired cardiac performance
      at 120 min after LPS challenge: the maximal rate of left ventricular pressure
      rise and fall (+/-dp/dt(max)) decreased compared with the control. In contrast,
      +/-dp/dt(max) at 120 min in hearts perfused with neutral sulfate berberine (1
      micromol/L) for 10 min followed by 20 min LPS (100 microg/mL) was greater than
      the corresponding value in the LPS group. CONCLUSION: Neutral sulfate berberine
      inhibits LPS-stimulated myocardial TNF-alpha production, impairs calcium cycling,
      and improves LPS-induced contractile dysfunction in intact heart.

PMID- 16412267
TI  - Effect of resveratrol on L-type calcium current in rat ventricular myocytes.
AB  - AIM: To study the effect of resveratrol on L-type calcium current (I(Ca-L)) in
      isolated rat ventricular myocytes and the mechanisms underlying these effects.
      METHODS: I(Ca-L) was examined in isolated single rat ventricular myocytes by
      using the whole cell patch-clamp recording technique. RESULTS: Resveratrol (10-40
      micromol/L) reduced the peak amplitude of I(Ca-L) and shifted the current-voltage
      (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40
      micromol/L) decreased the peak amplitude of I(Ca-L) from -14.2+/-1.5 pA/pF to 
      10.5+/-1.5 pA/pF (P<0.05), -7.5+/-2.4 pA/pF (P<0.01), and -5.2+/-1.2 pA/pF
      (P<0.01), respectively. Resveratrol (40 micromol/L) shifted the steady-state
      activation curve of I(Ca-L) to the right and changed the half-activation
      potential (V0.5) from -19.4+/-0.4 mV to -15.4+/-1.9 mV (P<0.05). Resveratrol at a
      concentration of 40 micromol/L did not affect the steady-state inactivation curve
      of I(Ca-L), but did markedly shift the time-dependent recovery curve of I(Ca-L)
      to the right, and slow down the recovery of I(Ca-L) from inactivation. Sodium
      orthovanadate (Na(3)VO(4); 1 mmol/L), a potent inhibitor of tyrosine phosphatase,
      significantly inhibited the effects of resveratrol (P<0.01). CONCLUSION:
      Resveratrol inhibited I(Ca-L) mainly by inhibiting the activation of L-type
      calcium channels and slowing down the recovery of L-type calcium channels from
      inactivation. This inhibitory effect of resveratrol was mediated by the
      inhibition of protein tyrosine kinase in rat ventricular myocytes.

PMID- 16412268
TI  - Thrombin-like enzymes from venom gland of Deinagkistrodon acutus: cDNA cloning,
      mechanism of diversity and phylogenetic tree construction.
AB  - AIM: To clone cDNAs of thrombin-like enzymes (TLEs) from venom gland of
      Deinagkistrodon acutus and analyze the mechanisms by which their structural
      diversity arose. METHODS: Reverse transcription-polymerase chain reaction and
      gene cloning techniques were used, and the cloned sequences were analyzed by
      using bioinformatics tools. RESULTS: Novel cDNAs of snake venom TLEs were cloned.
      The possibilities of post-transcriptional recombination and horizontal gene
      transfer are discussed. A phylogenetic tree was constructed. CONCLUSION: The
      cDNAs of snake venom TLEs exhibit great diversification. There are several types
      of structural variations. These variations may be attributable to certain
      mechanisms including recombination.

PMID- 16412269
TI  - MI-QSAR models for prediction of corneal permeability of organic compounds.
AB  - AIM: To derive a theoretical model for the prediction of corneal permeability of
      miscellaneous organic compounds in drug design. METHODS: A training set of 28
      structurally diverse compounds was used to build up the membrane-interaction
      quantitative structure-activity relationship (MI-QSAR) models. Intermolecular and
      intramolecular solute descriptors were computed using molecular mechanics,
      molecular dynamics simulations and quantum chemistry. The QSAR models were
      optimized using multidimensional linear regression fitting and a stepwise method.
      A test set of 8 compounds was evaluated using the models as part of a validation
      process. RESULTS: Significant MI-QSAR models (R=0.976, S=0.1301, F=70.957) of
      corneal permeability of organic compounds were constructed. Corneal permeability
      was found to depend upon the sum of net atomic charges of hydrogen atoms attached
      to the heteroatoms (N, O), the sum of the absolute values of the net atomic
      charges of oxygen and nitrogen atoms, the principal moment of inertia (X), the
      Connolly accessible area and the conformational flexibility of the solute
      membrane complex. CONCLUSION: The MI-QSAR models indicated that the corneal
      permeability of organic molecules was not only influenced by the organic solutes
      themselves, but also related to the properties of the solute-membrane complex,
      that is, the interactions of the molecule with the phospholipid-rich regions of
      cellular membranes.

PMID- 16412270
TI  - Relationship between atrial natriuretic peptide-immunoreactive cells and
      microvessels in rat gastric mucosa.
AB  - AIM: To investigate the ultrastructural localization of atrial natriuretic
      peptide (ANP)-synthesizing cells and the relationship between ANP-synthesizing
      cells and microvessels in rat gastric mucosa. METHODS: Immunohistochemistry
      techniques and postembedding immunoelectron microscopy techniques were used to
      validate the findings regarding the expression of ANP-synthesizing cells and the
      ultrastructural localization of ANP-synthesizing cells in the gastric mucosa.
      Histochemistry techniques and the tannic acid-ferric chloride method (TA-Fe
      staining method) were used to reveal microvessel density and the distribution of
      ANP-synthesizing cells in different regions of the stomach. RESULTS: Cells
      expressing ANP were localized and ANP-synthesizing cells were identified as
      enterochromaffin (EC) cells in the gastric mucosa. ANP-synthesizing cells existed
      in different regions of the stomach. The percentage ANP-synthesizing cells in the
      mucosa was greatest in the fundus (46.7%+/-5.3%), intermediate in the antrum
      (40.1%+/-4.5%), and least in the body (21.6%+/-3.6%). There was a positive
      relationship between the percentage of ANP-synthesizing cells and the density of
      microvessels in the antral mucosa, but not in the fundus or body mucosa.
      CONCLUSION: ANP is synthesized by EC cells in rat gastric mucosa, and ANP
      synthesizing cells are most dense in the gastric fundus. ANP may act not only as
      a regional autocrine and/or paracrine regulator, but also as an endocrine
      regulatory peptide in the gastrointestinal tract.

PMID- 16412271
TI  - Effects of orexins on myoelectric activity of sphincter of Oddi in fasted
      rabbits.
AB  - AIM: To investigate the effects of peripheral orexins on myoelectric activity of
      the sphincter of Oddi (SO) in fasted rabbits, and carry out a preliminary
      investigation into the mechanisms underlying these effects. METHODS: Myoelectric
      activity of SO in fasted rabbits was recorded before and after intravenous or
      local application of orexins. The effects of intravenous atropine on orexin
      increased myoelectric activity of SO were tested. RESULTS: Myoelectric activity
      of SO was activated by both intravenous and local injection of orexin-A or orexin
      B. Intravenous application of atropine completely inhibited the excitatory effect
      of orexins on SO. CONCLUSION: Peripheral application of orexins can increase
      myoelectric activity of SO in fasted rabbits, which is partially associated with
      the activation of the cholinergic pathway.

PMID- 16412272
TI  - Magnesium lithospermate B ameliorates renal cortical microperfusion in rats.
AB  - AIM: To investigate the effects of magnesium lithospermate B (MLB) isolated from
      Salviae miltiorrhizae on renal microcirculation, and renal and systemic
      hemodynamics in Sprague-Dawley rats. METHODS: MLB (10, 30, and 60 mg/kg) was
      injected intravenously and renal blood flow (RBF), renal cortical microperfusion
      (RCM), and systemic hemodynamic function parameters including heart rate (HR),
      mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left
      ventricular end-diastolic pressure (LVEDP), and maximal velocity of pressure
      increase (dp/dt(max)) were measured for 45 min after administration. RESULTS:
      Intravenous MLB at doses of 10, 30, and 60 mg/kg increased RCM significantly, but
      had no obvious effects on RBF or systemic hemodynamics. The effect of MLB on RCM
      reached its peak 15 min after injection and returned to baseline after 45 min. Up
      to 60 mg/kg MLB increased RCM by 62.4%+/-20.2% (changes from baseline, P<0.01),
      whereas RBF (3.7%+/-9.7% vs baseline) and renal vascular resistance (-1.4%+/-9.1%
      vs baseline) did not obviously change. CONCLUSION: These results indicate that
      MLB ameliorates renal microcirculation in a dose-dependent manner, which may be
      related to the renoprotective effects of MLB.

PMID- 16412273
TI  - C333H, a novel PPARalpha/gamma dual agonist, has beneficial effects on insulin
      resistance and lipid metabolism.
AB  - AIM: To examine the effects of novel peroxisome proliferator-activated receptor
      (PPAR) alpha/gamma dual agonist C333H on insulin resistance and lipid metabolism.
      METHODS: An established dual-luciferase reporter gene assay system was used in
      vitro to test the activity of C333H with respect to the transcription of human
      PPARalpha and PPARgamma. A preadipocyte differentiation assay and reverse
      transcription-polymerase chain reaction were used to detect the functional
      activities of C333H. In db/db mice, the effects of C333H were investigated with
      respect to lowering of blood glucose and lipid levels. RESULTS: C333H was
      determined to be a novel PPARalpha/gamma dual agonist because it strongly induced
      luciferase activity on human PPARalpha and PPARgamma, promoting the
      differentiation of preadipocytes to adipocytes, and functioning in upregulating
      the expression of some glucose and lipid metabolic target genes of the PPAR. In
      addition, C333H efficiently reduced blood lipid and glucose concentrations in
      db/db diabetic mice. CONCLUSION: C333H has dual action on both PPARalpha and
      PPARgamma, and might be of interest for the amelioration of lipid metabolic
      disorders and insulin resistance associated with type 2 diabetes.

PMID- 16412274
TI  - Effects of astragaloside IV on pathogenesis of metabolic syndrome in vitro.
AB  - AIM: To investigate the diverse pharmacological actions of astragaloside IV from
      the perspective of metabolic syndrome, and to investigate the effect of the drug
      on the pathogenesis of metabolic syndrome. METHODS: Adipogenesis was used as an
      indicator of the effect of astragaloside IV on preadipocyte differentiation, and
      was measured by using an oil red O assay. Glucose uptake was determined by
      measuring the transport of [2-(3)H]-deoxyglucose into the cells. The
      concentrations of peroxisome proliferator-activated receptor-gamma (PPARgamma)
      and aP2 mRNA were determined by using reverse transcription-polymerase chain
      reaction. Apoptosis and viability loss of endothelial cells were detected by
      using flow cytometry and the WST-1 assay, respectively. Intracellular free Ca2+
      was labeled with Fluo-3 AM and measured by using a laser scanning confocal
      microscope. RESULTS: Astragaloside IV can significantly potentiate insulin
      induced preadipocyte differentiation at concentrations of 3, 10, and 30
      microg/mL, improve high glucose-induced insulin resistance in adipocytes at a
      concentration of 30 microg/mL, and prevent tumor necrosis factor (TNF)-alpha
      induced apoptosis and viability loss at concentrations of 10 and 30 microg/mL,
      and 30 microg/mL, respectively, in endothelial cells. Furthermore, we found that
      these effects were partly due to the promotion of PPARgamma expression and to the
      inhibition of abnormal TNF-alpha-induced intracellular free Ca(2+) accumulation
      in endothelial cells. CONCLUSION: The diverse pharmacological actions of
      astragaloside IV can all be linked to metabolic syndrome pathogenesis. Our study
      provides a new insight into the mechanism by which astragaloside IV exerts its
      effect.

PMID- 16412275
TI  - Site-specific conjugation of bifunctional chelator BAT to mouse IgG1 Fab'
      fragment.
AB  - AIM: To perform a site-specific conjugation of Fab' fragments of a mouse
      monoclonal antibody(MoAb) B43(of IgG1 subtype) to a bifunctional chelator 6-[p
      (bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N',N' 'N' ' '
      tetraacetic acid (BAT) via the thiol groups in the hinge distal to the antigen
      binding site of the Fab'. METHODS: B43 was cleaved using a simple 2-step method.
      First, stable F(ab')(2) was produced by pepsin treatment. Fab' with free thiol in
      the hinge region was then obtained by cysteine reduction of F(ab')2. Second, a
      site-specific conjugation of Fab' to thiol-specific BAT was performed in a one
      step reaction. RESULTS: The Fab' fragment had approximately 1.8 free thiol groups
      per molecule after cysteine reduction. The conjugation efficiency and the
      chemical yield were approximately 1.28 moles chelator/Fab' and 74% of the initial
      concentration of Fab', respectively. The F(ab')2, Fab' and Fab'-BAT all
      maintained reasonable antigen-binding properties. (67)Cu labeling of the
      conjugate under standard conditions did not impair the immunoreactivity of Fab'
      BAT. CONCLUSION: This is a simple and efficient method for producing
      immunoreactive conjugates of Fab'-BAT, which can be used to make radiometal
      labeled conjugates for further diagnostic and therapeutic applications.

PMID- 16412276
TI  - Inhibition of Bcl-2 expression by a novel tumor-specific RNA interference system
      increases chemosensitivity to 5-fluorouracil in Hela cells.
AB  - AIM: RNA interference (RNAi) has been proposed as a potential treatment for
      cancer, but the lack of cellular targets limits its use in cancer gene therapy.
      No current technology has achieved direct tumor-specific gene silencing using
      RNAi. In the present study we attempt to develop a tumor-specific RNAi system
      using the human telomerase reverse transcriptase (hTERT) promoter; furthermore,
      we analyzed its inhibitive effect on Bcl-2 expression. METHODS: The vectors
      containing a small hairpin RNA (shRNA) to target exogenous reporters [firefly
      luciferase and enhanced green fluorescent protein (EGFP)] and endogenous gene
      (Bcl-2) were constructed. Luciferase expression was determined by dual luciferase
      assay. Reverse transcription-polymerase chain reaction (RT-PCR), fluorescence
      microscopy and fluorescence-activated cell sorting (FACS) were used to measure
      EGFP expression. Inhibition of Bcl-2 was evaluated by RT-PCR and Western
      blotting. Cell proliferation and viability were measured by using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. FACS was
      used to analyze the cell cycle distribution profile. RESULTS: We showed that with
      the hTERT promoter directly driving shRNA transcription, expression of the
      exogenous reporters (LUC and EGFP) in tumor cells, but not normal cells, was
      specifically inhibited in vitro. The hTERT promoter-driven shRNA also depressed
      the expression of Bcl-2. Inhibition of Bcl-2 did not affect cell proliferation,
      but increased the chemosensitivity of HeLa cells to 5-fluorouracil. CONCLUSION:
      The present study describes an efficient RNAi system for gene silencing that is
      specific to tumor cells using the hTERT promoter. Suppression of Bcl-2 by using
      this system sensitized HeLa cells to 5-fluorouracil. This system may be useful
      for RNAi therapy.

PMID- 16412277
TI  - Transport of carbamazepine and drug interactions at blood-brain barrier.
AB  - AIM: To investigate the characteristics of carbamazepine (CBZ) transport and drug
      interactions at the blood-brain barrier. METHODS: Cultured rat brain
      microvascular endothelial cells (rBMEC) were used as an in vitro model of the
      blood-brain barrier (BBB). When cells became confluent, CBZ uptake over time was
      recorded by incubation of the cells in a medium containing 10 mg/L CBZ at 37
      degree. The steady-state uptake of CBZ by rBMEC was tested for different CBZ
      concentrations at 37 degree. The effects of various agents on the steady-state
      uptake of CBZ and efflux of CBZ from rBMEC were also studied. RESULTS: The uptake
      of CBZ by rBMEC was time- and concentration-dependent. The steady-state uptake
      occurred at 30 min for incubation. The steady-state uptake was significantly
      increased (P<0.01) by treatment with dinitrophenol. The co-administration of
      cyclosporine A significantly increased the steady-state uptake of CBZ by the
      rBMEC, whereas co-administration of olanzapine significantly decreased the uptake
      in a concentration- and temperature-dependent manner. The efflux of CBZ from
      rBMEC was inhibited by CsA. CONCLUSION: The transport of CBZ at the BBB is
      mediated by many transporters. Some specific ABC (ATP-binding cassette, ABC)
      efflux transporters may be involved in the transport of CBZ. Drugs influence the
      transport of CBZ at the BBB in different ways.

PMID- 16412278
TI  - Distributive characteristics of Ser49Gly and Gly389Arg genetic polymorphisms of
      beta1-adrenoceptor in Chinese Han and Dai populations.
AB  - AIM: Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of beta(1)
      adrenoceptor may result in significant changes in the function of this receptor.
      The aim of the present study was to investigate the frequencies of the Ser49Gly
      and Gly389Arg mutant alleles in healthy Chinese populations and to investigate
      the differences between 2 Chinese ethnic groups (Han and Dai populations) with
      respect to the frequencies of these alleles. METHODS: A total of 225 Han Chinese
      and 175 Dai Chinese unrelated healthy volunteers were recruited for this study.
      Genomic DNA was extracted from peripheral blood leukocytes by using a standard
      manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were
      amplified by using polymerase chain reaction with template genomic DNA and
      relevant primers. The DNA products including the polymorphic loci were subjected
      to restriction endonuclease digestion with Eco0109I and BcgI. Digested fragments
      were detected with an ultraviolet detector after electrophoresis (100 V for
      approximately 1.5 h). RESULTS: The frequencies of the Gly49 and Arg389 alleles
      were, respectively, 16.2% and 76.4% in the Han population and 14.6% and 75.7% in
      the Dai population. CONCLUSION: The polymorphisms causing the Ser49Gly and
      Gly389Arg mutations of the beta(1)-adrenoceptor existed in both healthy Han and
      Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant
      alleles were not significantly different in the Han and Dai populations. However,
      the frequency of the Gly389 variant seems to be significantly lower in these 2
      populations than in an African-American population.

PMID- 16412282
TI  - [The assessment of curative effect after total mesorectal excision with autonomic
      nerve preservation for rectal cancer].
AB  - OBJECTIVE: To evaluate the impact on sexual function, local recurrence and
      survival after total mesorectal excision (TME) with autonomic nerve preservation
      (PANP) of rectal cancer. METHODS: One hundred and five patients after TME with
      PANP were followed by means of questionnaire on postoperative genital function
      [TME + PANP(+) group], and the results of 110 patients after TME without PANP
      [TME + PANP(-) group] were compared with, also their local recurrence and 5-year
      survival were retrospectively analyzed. RESULTS: TME + PANP(+) group was compared
      to TME + PANP(-) group: the erection dysfunction, 33.3% vs 63.2%; the ejaculation
      dysfunction, 43.8% vs 70.0% (P < 0.01), there were significant differences
      between two groups, but no difference in local recurrent rate and 5-year survival
      rate (7.6% vs 5.5%; 63.4% vs 59.7%, P > 0.05). CONCLUSION: The TME with PANP of
      rectal surgery ensure the radical cure of rectal cancer, at the same time
      reasonably save the postoperative sexual function and obtain satisfactory
      postoperative survival.

PMID- 16412283
TI  - [The excision of right hemicolonic carcinoma with anterograde clearance to lymph
      nodes].
AB  - OBJECTIVE: To investigate the essentials of operation and the postoperative
      effect of right hemicolonic carcinoma with anterograde clearance of lymph nodes.
      METHODS: One hundred and thirty-five patients with right hemicolonic infiltrated
      carcinoma, who were eligible for radical excision (D(3)), were divided into 2
      groups. Among them, the anterograde clearance of lymph nodes was performed on 56
      cases; the retrograde clearance was performed on 79 cases. Both groups showed no
      significant difference in age, sex, Dukes' staging and pathological type.
      RESULTS: The average time of operation: the anterograde group was (180 +/- 40)
      min; the retrograde group was (180 +/- 20) min. The average amount of bleeding:
      the anterograde group was (200 +/- 80) ml; the retrograde group was (200 +/- 30)
      ml. The cleared number of lymph nodes: the anterograde group were 6.3 +/- 4.2,
      2.6 +/- 3.1, 1.5 +/- 2.3 in paracolon, middle and radicel of vasorum
      respectively, the total number was 11.4 +/- 8.6; the retrograde group were 6.4 +/
      2.2, 2.8 +/- 2.1, 1.1 +/- 1.1 respectively, the total number was 10.8 +/- 5.6 (P
      > 0.05). The postoperative metastasis to liver: the anterograde group was 8 cases
      (13.9%); the retrograde group was 21 cases (26.6%, P < 0.05). The 5-year survival
      rate: the anterograde group was 72.8% (41/56); the retrograde group was 65.5%
      (52/79) (P < 0.05). CONCLUSIONS: The operative technique of the excision was
      little difficulty and complexity, and it could fit well with the requirement of
      non touch isolation, and act to cut down the postoperative metastasis to liver
      and to elevate 5-year survival rate.

PMID- 16412284
TI  - [Analysis of the relationship between stoma position and postoperative effects of
      procedure for prolapse and hemorrhoids in the treatment of hemorrhoids].
AB  - OBJECTIVE: To explore the relationship between stoma position and postoperative
      effects of procedure for prolapse and hemorrhoids (PPH) in the treatment of
      hemorrhoids. METHODS: Four hundred and one hemorrhoid patients were treated with
      circular stapler. II hemorrhoids, 45 cases; III-IV hemorrhoids, 356 cases. The
      position of stoma located 1 cm up dentate line, 219 cases; 1-2 cm up dentate
      line, 87 cases; 2-3 cm up dentate line, 60 cases; 3-4 cm up dentate line, 25
      cases; > 4 cm up dentate line, 10 cases. The patients were followed from one week
      to two years postoperatively. RESULTS: Postoperative effects and procidentia
      rates have significant association with the position of stoma. If the distance
      between position of stoma and dentate line is < or = 2 cm, the postoperative
      procidentia rate was 1.1%, lower than that of the distance > or = 4 cm.
      CONCLUSIONS: The complication and procidentia rate of PPH is associated with the
      stoma position. The stoma position should be no more than 2 cm to dentate line.

PMID- 16412285
TI  - [Retrograde caudate lobectomy in 7 cases].
AB  - OBJECTIVE: To explore the clinical value and significance of retrograde caudate
      lobectomy. METHODS: From December 2003 to January 2005, 7 patients underwent
      retrograde caudate lobectomy in which division and ligation of short hepatic
      veins were carried out at the final stage of the procedure in stead of at the
      initial stage. RESULTS: The procedures were carried out smoothly with no
      operative death in all the 7 cases including isolated complete caudate lobectomy
      in 4 cases, isolated partial caudate lobectomy in 1 case, combined right half
      liver resection in 2 case. The average operation time, blood loss and length of
      stay after operation was (273 +/- 44) min, (1114 +/- 241) ml (800-1500 ml) and 16
      days respectively. Complications including pleural effusion and ascites in 1 case
      respectively were fully recovered. During the follow-up, 1 patient died at 6
      months for tumor recurrence in lung and the remaining 6 patients are alive at the
      follow-up of 5 to 16 months. CONCLUSIONS: Retrograde caudate lobectomy is a new
      procedure suitable for those caudate neoplasms which are adhering to or
      infiltrating to IVC or too big to move side by side. The application of this
      technique can converse certain kind of caudate lobe tumor from non-resectable to
      resectable resulting in widening the indication.

PMID- 16412286
TI  - [Diagnosis and treatment of cytomegalovirus pneumonia after liver
      transplantation].
AB  - OBJECTIVES: To investigate the diagnosis and treatment of cytomegalovirus (CMV)
      pneumonia after liver transplantation. METHODS: Five cases of CMV pneumonia after
      liver transplantation were analyzed retrospectively. CMV pneumonia was diagnosed
      according to its clinical manifestation, chest X-ray, and etiologic test. All 5
      patients received comprehensive therapy based on anti-virus treatment and
      immunologic adjustment. RESULTS: The clinical manifestation of CMV pneumonia
      after liver transplantation was nonspecific. Its main symptoms included fever,
      cough, dyspnea, tachycardia, fatigue, hypoxemia and neutropenia. The chest X-ray
      showed interstitial pneumonia. Sera CMV antigens or antibodies could be detected
      in the patients. Four patients were cured and 1 patient died. CONCLUSIONS: The
      clinical manifestation of CMV pneumonia was nonspecific. CMV pneumonia could be
      diagnosed according to its manifestations, chest X-ray and etiologic test. The
      comprehensive therapy based on anti-virus treatment and immunologic adjustment
      was effective for the disease.

PMID- 16412287
TI  - [Clinical analysis of medullary carcinoma of the breast].
AB  - OBJECTIVE: To assess the clinical manifestation, management and outcome in
      patients with medullary carcinoma of the breast (MBC). METHODS: Retrospective
      analysis was carried out on patients with MBC who were admitted from January 1995
      to December 1999. RESULTS: A total of 616 female patients treated for breast
      carcinoma, 26 cases (4.2%) were histopathologically confirmed MBC. The mean age
      was (45.8 +/- 10.6) years. The tumor size was among 1-5 cm and axillary lymph
      node involvement was 23.1%; there was no statistically significant correlation
      between tumor size and metastatic axillary lymph node. Estrogen receptor (ER),
      progesterone receptor (PR) and HER-2/neu assay were performed
      immunohistochemically, and the overexpression was 26.3%, 21.1% and 5.3%
      respectively. All patients underwent operation and polychemotherapy (5
      fluorouracil, methotrexate, cyclophosphamide), hormone therapy with Tamoxifen was
      applied in five patients, and three cases received postoperative irradiation. The
      follow-up period ranged from 5 to 9 years. Overall five-year survival was 88.4%.
      CONCLUSIONS: MBC is a favorable histological type of breast carcinoma with good
      prognosis. Operation and chemotherapy are main procedures for MBC. The
      significance of molecular biologic parameters in the prognosis of MBC should not
      be overlooked.

PMID- 16412288
TI  - [Clinical study of percutaneous ultrasound-guided or freehand core needle biopsy
      of primary breast cancer].
AB  - OBJECTIVE: To evaluate ultrasound-guided or freehand percutaneous core needle
      biopsy in histopathological assessment of primary breast cancer lesions and its
      utility in primary breast cancer treatment. METHODS: Retrospectively analysis of
      the clinical data of 697 primary breast cancer examined by mean of core needle
      biopsy. RESULTS: The diagnostic accuracy, false negative rate and insufficiency
      rate was 90.5%, 8.9% and 0.6%, respectively. Diagnostic accuracy was
      significantly higher in ultrasound guiding comparing to palpable guiding (92.7%
      vs. 88.2%, P < 0.05). There was a nonsignificant trend toward increased false
      negative rate in palpable guiding (10.9% vs. 7.1%, P > 0.05). CONCLUSION:
      Percutaneous core needle biopsy is reliable in histopathological assessment of
      primary breast cancer lesions. Ultrasound guiding was superior to palpable
      guiding in term of diagnostic accuracy in this study.

PMID- 16412290
TI  - [Chinese medicine Extractum trametes robiniophila murr augment tumor necrosis
      factor related apoptosis-inducing ligand induced apoptosis in human hepatic
      cancer cell lines].
AB  - OBJECTIVE: To investigate the effects of tumor necrosis factor related apoptosis
      inducing ligand (TRAIL) combined with Chinese medicine, Extractum trametes
      robiniophila murr in human hepatic cancer cells. METHODS: HepG2 cell line
      resistant to adriamycin (HepG2/ADR) was induced step by step. The effects of
      TRAIL (100 ng/L) combined with Extractum trametes robiniophila murr (1.0 g/L)
      promoting apoptosis in HepG2 or HepG2/ADM were analyzed. The proliferation was
      observed by MTT assay and the apoptosis of cells was also observed by flow
      cytometry. RESULTS: HepG2/ADM was confirmed resisting to ADM. The treatment of
      TRAIL (100 ng/L) combined with Extractum trametes robiniophila murr (1.0 g/L)
      showed significant inhibitory effects on the growth of both HepG2 and HepG2/ADM,
      and the percentage of apoptosis was increased compared with other groups within
      24 to 72 h. CONCLUSIONS: Extractum trametes robiniophila murr dramatically
      augmented the sensitivity of both HepG2 and HepG2/ADM to TRAIL, but only has
      slightly killing effects on L02. TRAIL combined with Chinese medicine treatment
      could be a safe and attractive strategy to drug-resistant/TRAIL-resistant tumor
      cells.

PMID- 16412291
TI  - [Hypermethylation of Ras association domain family protein 1A, hypermethylated in
      cancer 1 and p73 genes in hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the status of promoter hypermethylation of Ras association
      domain family protein 1A (RASSF1A), hypermethylated in cancer 1 (HIC1) and p73
      genes in hepatocellular carcinoma (HCC) and to explore the correlation with
      clinicopathological features. METHODS: Forty cases of HCC and their corresponding
      non-tumor liver tissues, other 2 cases of healthy donor livers were detected
      using methylation specific polymorphism chain reaction (MSP) method. RESULTS: The
      frequency of promoter hypermethylation of RASSF1A showed 90.0% and 72.5% in tumor
      and corresponding non-tumor tissues respectively, and there was significant
      difference between them (P < 0.05). The frequency of promoter hypermethylation of
      HIC1 showed 77.5% and 70.0% in tumor and corresponding non-tumor tissues
      respectively. The frequency of hypermethylation of HIC1 in non-tumor liver
      tissues showed significant correlation between younger and older patients. The
      frequency of promoter hypermethylation of p73 showed 5.0% in tumor tissues.
      However, none of hypermethylation of the gene was detected in corresponding non
      tumor liver tissues. There was none of hypermethylation of the three genes showed
      in two cases of healthy donor livers. CONCLUSION: Promoter hypermethylation of
      RASSF1A and HIC1 genes are common event in HCC and play an important role in the
      pathogenesis and may be used to develop novel diagnostic and therapeutic
      approaches for HCC in the future.

PMID- 16412292
TI  - [Protective effect of ischemic postconditioning on ischemic reperfusion injury of
      rat liver graft].
AB  - OBJECTIVE: To observe the protective effect of ischemic postconditioning on
      ischemic reperfusion injury of rat liver graft and to investigate the possible
      mechanism. METHODS: Male Sprague Dawley rats were used as donors and recipients
      of orthotopic liver transplantation, and the period of cold preservation and
      anhepatic phase were 100 min and 18 min, respectively. Sixty rats were randomly
      divided into three groups, twelve rats in control group, twenty-four rats in
      ischemic reperfusion injury group and ischemic postconditioning group
      respectively. Control group is sham operation group, only the ligaments around
      liver were cut off; donor livers in ischemic reperfusion injury group were
      infused through portal vein with heparinized saline before harvested; ischemic
      postconditioning group: at very onset of reperfusion after donor liver was
      implanted, several brief reperfusion-ischemia were given before persistent
      reperfusion of portal vein. Half recipients of ischemic reperfusion injury group
      and ischemic postconditioning group were taken blood samples and hepatic tissue
      samples after 2 hours of reperfusion of liver graft. Rest recipients were taken
      samples of hepatic tissue after 6 hours of reperfusion. Recipients of control
      group were taken blood and hepatic tissue samples at corresponding time after
      abdomen was sutured. RESULTS: Compared with ischemic reperfusion injury group,
      liver functional parameters, cytokines and peroxidized products contents were
      lower in ischemic postconditioning group (P < 0.05); meanwhile, the antioxidases
      contents of hepatic tissue were higher in ischemic postconditioning group than
      those in ischemic reperfusion injury group (P < 0.05). CONCLUSIONS: Ischemic
      postconditioning could relieve the ischemic reperfusion injury of rat liver
      graft. Through improving antioxidation capability and cutting down cytokines
      contents, ischemic postconditioning could apply its protective effect.

PMID- 16412293
TI  - [Expression of nestin and neurogenin 3 in the human fetal pancreas].
AB  - OBJECTIVE: To examine the expression of nestin and neurogenin 3 (Ngn3), the
      markers of pancreatic stem cells, in the human fetal pancreas. METHODS: The human
      fetal pancreas tissue of 12 and 14 weeks were examined for the expression of
      nestin and Ngn3 using the techniques of immunofluorescence dye and RT-PCR.
      RESULTS: Both nestin and Ngn3 expressed widely in 12 and 14 weeks before in human
      fetal pancreatic tissue. In these positive cells there was no co-expressing
      insulin or glucagon. There were nestin and Ngn3 co-expressing cells in ducts but
      not in the islets. The results of RT-PCR also indicated the expression of nestin
      and Ngn3. CONCLUSIONS: There was no expression of the markers of mature endocrine
      cells in the nestin and Ngn3 positive cells, and they were the marks of no
      differentiation cells in the human fetal pancreatic tissue.

PMID- 16412294
TI  - [Effect of interleukin-8 in cell invasion and proliferation of human breast
      cancer].
AB  - OBJECTIVE: To identify the effect of interleukin-8 in cell progression and
      invasion of human breast cancer. METHODS: Human cytokine antibody arrays were
      applied to screen a panel of cytokine expression from 11 human breast cancer cell
      lines, and the mechanism of identified key factors involved in breast cancer
      progression was studied. RESULTS: Profiling of cytokine expression showed the
      expression of interleukin-8 was related to estrogen receptor status, metastasis
      and vimentin status in the 11 human breast cancer cell lines. Elevated expression
      of interleukin-8 in breast cancer cells had positive correlation with breast
      cancer invasion. Neutralization of antibody against interleukin-8 specifically
      blocked interleukin-8-mediated cell invasion. However, anti-interleukin-8
      antibody did not influence the proliferation of breast cancer cells. CONCLUSION:
      Interleukin-8 may be the key factor involved in human breast cancer progression
      and invasion, and play an important role in cell invasion of breast cancer.

PMID- 16412295
TI  - [The synergistic inhibitory effect of 5-aza-2-deoxycytidine and Tamoxifen on
      estrogen receptor alpha negative breast cancer cell lines in vitro].
AB  - OBJECTIVE: To observe if ER alpha gene can be induced by 5-aza-CdR in ER alpha
      negative human breast cancer cell lines (MDA-MB-231 and MDA-MB-435) and the
      synergistic inhibitory effects of 5-aza-CdR and Tamoxifen on these two cell lines
      in vitro. METHODS: The status of 5'CpG island methylation of ER alpha gene in ER
      alpha negative (MDA-MB-231 and MDA-MB-435) human breast cancer cell lines and 20
      cases of breast cancer tissue was studied by MSP, the expression of ER alpha mRNA
      was inspected by using RT-PCR after these two cell lines were treated with 5-aza
      CdR. Cell proliferation was evaluated by MTT assay, distribution of cell cycle
      and rate of apoptosis were determined by flow cytometry after these two cell
      lines were treated with 5-aza-CdR or TAM alone, or in combination in vitro.
      RESULTS: The 5'CpG island is methylated in the core promotor of ER alpha gene in
      ER alpha negative (MDA-MB-231 and MDA-MB-435) human breast cancer cell lines and
      the methylating rate is 25.0%, 66.7%, 83.3%, 100% in 20 cases of breast cancer
      tissue of stage I, II, III, IV, respectively. The expression of ER alpha mRNA was
      induced in these two cell lines after treated with 5-aza-CdR, MTT array showed
      the proliferation activity of these two cell lines was obviously reduced in 5-aza
      CdR group and the inhibitory effect on proliferation was enhanced when 5-aza-CdR
      combined with TAM compared with control group, the induction of apoptosis was
      11.20% and 8.71% respectively by 5-aza-CdR, while the rate of apoptosis is 48.8%
      and 53.1% when these two cells were treated with 5-aza-CdR combined with TAM.
      CONCLUSIONS: 5-aza-CdR can re-express ER alpha by demethylating and sensitive ER
      alpha negative human breast cancer cell lines to TAM, 5-aza-CdR and TAM
      synergistically inhibit proliferation and induce apoptosis in ER alpha negative
      human breast cancer cell lines, thus offer a new way for the treatment of ER
      alpha negative breast cancer.

PMID- 16412301
TI  - [The effect of titanium mesh cage on maintenance of thoracolumbar and lumbar
      lordosis in anterior instrumentation for thoracolumbar and lumbar scoliosis].
AB  - OBJECTIVE: To evaluate the clinical importance of titanium mesh cage (TMC) in
      anterior instrumentation for scoliosis. METHODS: Thirty-six consecutive patients
      with thoracolumbar/lumbar adolescent idiopathic scoliosis were treated with
      anterior derotation and instrumentation using autologous bone grafting and TMC
      for interbody fusion. The average age of patients was 17 years (ranged from 14 to
      22 years), in which 5 cases were male and 31 cases were female. RESULTS: The
      coronal Cobb angle before surgery, 2 weeks after surgery, and 13 months at the
      follow-up was measured as 56 degrees , 15 degrees , and 18 degrees respectively,
      while the thoracic kyphosis from T(5) to T(12) was 30 degrees , 33 degrees , and
      37 degrees respectively, and the lumbar lordosis from L(1) to S(1) was 46 degrees
      , 56 degrees , 51 degrees . There were no death, infection, implant failures or
      collapse of intervertebral space. Intraoperative injury of lacteal occurred in
      one patient, but no postoperative complications happened. One of two patients who
      had pleural effusion was managed with close drainage. Exudative pleurisy occurred
      in one patient, the sympathectomy effect occurred in three patients who presented
      asymmetry of skin temperature and resolved in short term. CONCLUSIONS: Coronal
      and sagittal alignment can be well corrected and maintained with TMC in anterior
      scoliosis surgery, collapse of intervertebral space and lumbar kyphosis can be
      prevented.

PMID- 16412302
TI  - [The study of treatment of osteoporotic thoracolumbar multi-vertebral compressive
      fractures by kyphoplasty with one balloon].
AB  - OBJECTIVE: To evaluate the effect of kyphoplasty in treating osteoporotic
      thoracolumbar multi-vertebral compressive fractures with one balloon. METHODS:
      thirteen cases (37 vertebral bodies) of osteoporotic thoracolumbar multi
      vertebral compressive fractures were treated. The patients were women, range 65
      to 79 years old, and all with well intact posterior wall of vertebral body. 37
      thoracolumbar vertebral bodies were treated by Kyphoplasty with one balloon under
      "C" armed imaging guiding. RESULTS: All 13 patients tolerated well. The mean
      height of the anterior, media and posterior vertebral bodies was (1.9 +/- 0.5)
      cm, (1.5 +/- 0.5) cm, (2.6 +/- 0.5) cm preoperatively and (2.1 +/- 0.4) cm, (2.2
      +/- 0.4) cm, (2.8 +/- 0.5) cm postoperatively (P < 0.001). The mean kyphosis was
      improved from (31.3 +/- 14.1) degrees to (24.8 +/- 11.3) degrees. There was not
      back pain and deformed correction was maintained well after 17.3 months' follow
      up, No complication occurred. CONCLUSION: The balloon was not damaged, because
      the pressure was lower than usual pressure, the cost of patients was saved. In
      this study, we fulfilled small amount of cement in vertebral body which reduced
      the leakage of cement. Fracture of close vertebral body was also reduced because
      of lower stiffness and modulus of elasticity of adjacent vertebral body.

PMID- 16412303
TI  - [A new kind of grade system for thoracic pedicle screw placement and its clinical
      purpose].
AB  - OBJECTIVE: To introduce a new kind of grade system for thoracic pedicle screws
      placement by performing postoperative computerized tomography (CT) scanning and
      discussion the clinical purpose. METHODS: Four hundred and fifty thoracic pedicle
      screws were implanted in 64 patients with the assistance of fluoroscopy.
      Postoperative CT scanning was conducted to determine a grade for each screw: Part
      A, screw entirely contained within pedicle; Part B(1), violate lateral or upper
      pedicle but screw tip entirely contained within the vertebral body (VB); Part
      B(2), violate medial or inferior of pedicle; Part B(3), tip penetrated anterior
      or lateral VB; Part C, violate pedicle or VB and endangers spinal cord, nerve
      roots, or great vessels. Based on anatomical morphometry, thoracic vertebral were
      subdivided into upper (T(1 - 2)), middle (T(3 - 6)), and lower (T(7 - 12))
      regions. The mean follow-up period was 25.8 months. RESULTS: The postoperative CT
      scanning-documented grade were determined: Part A, 367 screws (81.6%); Part B, 78
      (17.3%), B(1) 40 (8.1%); Part B(2), 23 (5.1%); Part B(3), 15 (3.4%); Part C, 5
      (1.1%). There were not significant difference between upper and lower thoracic
      that the placement of pedicle screws in part B or C. In part C, 5 pedicle screws
      were all in the middle thoracic. CONCLUSION: Postoperative CT scanning should be
      considered as a routine examination for evaluating thoracic pedicle screw
      placement.

PMID- 16412304
TI  - [Long-term results of combined therapy for primary osteosarcoma in extremities of
      189 cases].
AB  - OBJECTIVE: To evaluate the survival rates and complications of combined therapy
      for primary osteosarcoma of the extremities between 1992 and 2001. METHODS: From
      1992 to 2002, 189 patients with non-metastatic osteosarcoma were treated. Their
      average age at diagnosis was 18 years old (ranging from 4 to 39). Tumors were
      located at distal femurs in 86 patients, proximal femurs in 4, proximal tibia in
      52, proximal humors in 19 and other locations in 28. Combined therapy (resection
      of tumor with chemotherapy) was given 116 patients and non-combined therapy
      (tumor resection only and unfinished chemotherapy) to 73. In combined therapy
      group, 90 patients underwent limb salvage surgery, and 26 patients received
      amputations. In non-combined therapy group, 42 patients underwent limb salvage
      surgery and 31 patients received amputations. RESULTS: The 5-year-survival rates
      were 78.5% in the combined therapy group and 35.1% in the non-combined therapy
      group. Local recurrence rate was 16.6% (15 cases) in limb salvage surgery with
      combined therapy group (90 cases) and 38.1% (16 cases) in limb salvage surgery
      with non-combined therapy group (42 cases) (P < 0.007). Metastasis rate was 28.4%
      (33 cases) in the combined therapy group (116 cases) and 65.7% (48 cases) in the
      non-combined therapy group (73 cases) (P < 0.000). Functional evaluation showed
      that the patients who underwent salvage surgery had higher functional scores than
      those who had an amputation. According to MSTS scoring system (1993), 56 patients
      (excision alcohol replacement 36 cases, allograft 10 cases and prosthesis 10
      cases) were evaluated functional scores. The average scores reached same level (P
      > 0.5). CONCLUSIONS: (1) In this study, the 5-year-survival rate in the combined
      therapy is improved. The treatment for the patients with metastasis in lung is
      very difficult for improvement of the 5-year-survival rate. (2) The local
      recurrence is related the surgical margin. The adequate surgical margin is very
      important for the limb salvage. (3) The combined therapy is very essential for
      improving survival rate.

PMID- 16412305
TI  - [Percutaneous cannulated screws internal fixation for treating the posterior
      portion of the iliac wing fractures].
AB  - OBJECTIVE: To present the technique for percutaneous placement of cannulated
      screws in the iliac wing, and to describe the surgical technique and the methods,
      the indication, the time, the key of operation and the clinic outcomes of the
      technique. METHODS: Through the anatomy study of ilium, a wider columns structure
      at the posterior ilium was found, which was named "the posterior columns of
      pelvis", and then measure the parameter of the structure. Twelve patients with
      the injuries in the iliac wing and the anterior ring of pelvis were treated with
      percutaneous cannulated screws internal fixation. RESULTS: All of the fractures
      healed in the followed up period. Vertical replacement were all completely
      corrected. Two of the cases left behind slight rotary replacement, and no
      complication were found. CONCLUSIONS: The technique of percutaneous cannulated
      screws internal fixation for treating the posterior portion of the iliac wing
      fractures has the advantages of small trauma, less bleeding stiff fixation, which
      is an ideal and minimally invasive technique.

PMID- 16412306
TI  - [Computerized three-dimensional reconstruction and morphologic measurement of
      adult acetabulum bone structure].
AB  - OBJECTIVE: To set up three-dimensional reconstruction of acetabulum bone
      structure from CT scanned image in computer with software of CAD and study
      quantitatively the morphologic features of the acetabulum. METHODS: Through the
      process of CT scanning, and edge recording of the CT image, we made use of CAD
      software and Unigraphics software to reconstruct the 40 normal acetabulum bones
      for the radius of acetabulum (R), minimum thickness of medial wall of acetabulum
      (L), depth of Harris fossa (D) and maximum opening rim width in cross-sectional
      plane (W). RESULTS: The average R was 30.48 +/- 2.05 mm. The average L was 2.35
      +/- 1.13 mm. The average D was 5.71 +/- 1.21 mm. The average W was 63.06 +/- 2.05
      mm. There was a linear relationship between the R and the W, but no correlation
      between the R, the L and the D. CONCLUSIONS: There was a significance linear
      relationship between the R and the W in normal adult acetabulum. However no
      correlation between the R, the L and the D.

PMID- 16412307
TI  - [Anatomical study about the posterior coaxial portals via posterior tibial tendon
      sheath for ankle arthroscopy].
AB  - OBJECTIVE: To conduct the anatomical study about the posterior coaxial portals
      via posterior tibial tendon (PTT) sheath for ankle arthroscopy. METHODS: Coaxial
      portals were established in 20 ankles by K-wires which were left in place for
      distance measurement between them and the posterior nerves, tendons and vessels.
      Ankle arthroscopy was performed in 5 fresh ankles using 2.7 mm 300 arthroscopy
      with the same portals as mentioned above. The maximum visible scope were recorded
      and the distance between the arthroscopy and the posterior nerves, tendons and
      vessels was also measured. RESULTS: The medial portal was located 5 - 12 mm
      (average, 8 mm) above the tip of medial malleolus, and the lateral portal was
      located 8 - 24 mm (average, 15 mm) above the tip of lateral malleolus. The
      coaxial portals, which traversed the PTT sheath and passed posterior to the
      fibular, not only separated the arthroscopy and instrument from the posterior
      nerves, tendons and vessels by posterior capsule but also enlarged their
      distance. The medial and lateral malleolus articular gap, the posterior capsule
      could be viewed by these portals with as much as 1/2 - 2/3 posterior articular
      surface of talus. Not only the tibiotalar articular gap but also the dynamic
      movement between the mortise and the talus were clearly observed. Arthroscopic
      operation could be performed by instrument through the posterolateral portal.
      CONCLUSIONS: The posterior coaxial portals via PTT sheath for ankle arthroscopy
      have such advantages as easy maneuverability, superior safety, clear vision and
      larger operation field under arthroscopy.

PMID- 16412308
TI  - [Experimental study of bFGF modulating rabbit articular chondrocytes cultured in
      vitro and seeded onto polylactic acid scaffold coated with different materials].
AB  - OBJECTIVE: Culturing rabbit articular chondrocytes in vitro and seeding on
      polylactic acid (PLA) coated with lecithin and poly-l-lysine modulated by bFGF to
      find a suitable method for cartilaginous tissue engineering. METHODS: The
      articular chondrocytes were isolated enzymatically from the articular cartilage
      of young rabbits, and cultured in vitro. Collecting the chondrocytes of the third
      passage and seeding on three-dimensional scaffold of polylactic acid coated with
      lecithin and poly-l-lysine. At the same time, basic fibroblast growth factor
      (bFGF) was added. Proceeding series of detections when the cell-scaffold
      complexes were cultured more than two weeks, such as macroscopic, invert
      microscope, light microscope, scanning electron microscope and
      immunohistochemistry of collagen II. RESULTS: The cell-scaffold complexes
      modulate by bFGF could not only keep their original shapes, but also maintain the
      stable homogeneous three-dimensional distribution of chondrocytes without cell
      falling during the cultivation. At the same time, the complexes were gradually
      decreasing the consistency, however, increasing the Pliability with elasticity
      and lubrication surface. After the second week, the complexes were gradually
      reorganized into the mature engineered cartilage with typical cartilaginous
      histological structure with rich collagen II. CONCLUSION: bFGF can facilitate the
      regeneration and maturation of tissue-engineered articular cartilage.

PMID- 16412309
TI  - [Periosteum construction in vitro by small intestinal submucosa combined with
      bone marrow mesenchymal stem cell].
AB  - OBJECTIVE: To investigate the practicability of periosteum construction in vitro
      by small intestinal submucosa (SIS) as a tissue scaffold with bone marrow
      mesenchymal stem cells (BMSC). METHODS: The bone marrow mesenchymal stem cells
      were cultivated by the conventional method in vitro, and then co-cultivated with
      SIS. The morphological feature of the complex material, the extracellular
      matrices, the adhesion and proliferation of BMSC were observed by optical
      microscope, electronic microscope, scanning electronic microscope and histologic
      evaluation respectively. RESULTS: BMSCs adhered and proliferated on SIS, secreted
      a great deal of extracellular matrices with active cellular function. BMSCs grew
      well there in layers, and the thickness became thicker as time passed, acting
      like a biological periosteum. CONCLUSION: Combined culture of SIS and BMSC in
      vitro can construct a tissue engineering periosteum similar to the natural one,
      thus providing a base for further study of its osteogenic regeneration in vivo.

PMID- 16412310
TI  - [The effect of rupture and reconstruction of posterior cruciate ligament on the
      degeneration of articular cartilage in rabbit knee].
AB  - OBJECTIVE: To investigate the effect of rupture and reconstruction of the
      posterior cruciate ligament (PCL) on the degeneration of rabbit knee joint.
      METHODS: Thirty-three mature New Zealand white rabbits were divided into 3
      groups. In experiment group I, the PCL of the right knees in 21 rabbits were
      resected, the contralateral joints as control group, in which only a medial
      arthrotomy was performed. In experiment group II, the PCL of the right knees in
      12 rabbits were immediately reconstructed after PCL were resected. In experiment
      group I and control group the rabbits were respectively killed 6, 12 and 26 weeks
      after the operation. In experiment group II the rabbits were respectively killed
      12, 26 weeks after the operation. The methods of ink staining, histology,
      immunohistochemistry and SEM were used to analyze the changes of articular
      cartilage of the joints. RESULTS: In experiment group I, the knee joints had
      obvious degeneration of articular cartilage at 26 weeks. The quantitative
      analysis of the results of the ink staining method showed the degeneration of
      knee articular cartilage was more serious at 26 weeks than that at 26 weeks in
      control group. Histological results demonstrated: the large area of fibrosis of
      cartilage could be seen in the medial condyle at 26 weeks; the fibrosis was deep
      into the deep layer of cartilage and the number of cells decreased; the average
      Mankin's score was 7.7. At 26 weeks, type I and III collagen were detected in
      fibrotic cartilage, while the staining of type II collagen was slight. In
      experiment group I, the injuries of cartilage in medial condyle could be seen at
      every stage through SEM, while the surface of cartilage demonstrated disorder in
      control group through SEM. In experiment group II, only a few specimens had mild
      injuries of cartilage, the degeneration of cartilage in medial condyle and
      trochlea were slighter at 26 weeks than that in experiment group I. CONCLUSIONS:
      PCL rupture can result in articular cartilage degeneration, which develops as
      time goes on. The degeneration of articular cartilage is more serious in medial
      compartment and patellofemoral joint than those in other positions. Immediate
      reconstruction of PCL can effectively prevent articular cartilage degeneration.

PMID- 16412311
TI  - [An experimental study on biomechanical effects due to unilateral cortical bone
      defect in long tubular bone].
AB  - OBJECTIVE: To investigate the biomechanics effect due to unilateral cortical bone
      defect of different size in long tubular bone. METHODS: Seventy-six pieces of
      Sanhuang cock tibial were randomly divided into 7 groups. The unilateral
      diaphyses cortical were drilled holes of different size, include 1.5, 2.0, 2.5,
      3.0, 3.5, and 4.5 mm, performed three-points bend single experiment. The intact
      bone cortical group was control group. RESULTS: When there were bone structure
      destructions, the maximum of the bend load between 3 groups which bone defect
      diameter were 1.5 mm, 2.0 mm, and control was not significant difference (P =
      0.824, 0.865), but the maximum of the bend load between 3 groups which bone
      defect diameter were 2.5, 3.0, and 3.5 mm decreasing about 14 percent of the
      control group (P = 0.015, 0.010, 0.021). and the maximum of the bend load which
      bone defect diameter were 4.5 mm decrease about 23 percent of the control group
      (P = 0.001). CONCLUSIONS: If the diameter of bone cortical defect is within 22.63
      +/- 1.39 percent of bone cortical outer diameter, there was no reduction of the
      bend load. If the diameter of bone cortical defect is beyond 29.36 +/- 2.07
      percent of bone cortical outer diameter, it decreases the maximum bend load of
      the long tubular bone, but the reduced range is not complete with direct ratio to
      the bone defect size.

PMID- 16412312
TI  - [Expression of integrin alpha5 and actin in the cells of intervertebral disc
      under cyclic hydrostatic pressure in vitro].
AB  - OBJECTIVE: To investigate the expression of integrin alpha5 and actin in the
      cells of intervertebral disc under cyclic hydrostatic pressure in vitro. METHODS:
      The porcine lumbar intervertebral disc cells were isolated and cultured in vitro,
      and the cells underwent cyclic hydrostatic loading. After that, the expression of
      integrin alpha5 and actin in intervertebral disc cells were studied by means of
      morphology observing, Western blot and immunohistochemistry staining. RESULTS:
      The morphology of intervertebral disc cells were changed into smaller and flatten
      shape, and the expression of integrin alpha5 and actin were decreased after
      loading. CONCLUSIONS: The expression of integrin alpha5 decreases under cyclic
      hydrostatic pressure, and the actin is affected at the same time when signals are
      transferred into the cells by integrin alpha5. That may be one of the important
      mechanisms of the mechanotransduction in the cells of intervertebral disc.

PMID- 16412313
TI  - [The effects of brain-derived neurotrophic factor gene-modified neural stem cells
      on primary cultured dorsal root ganglion cells in vitro].
AB  - OBJECTIVE: To gain stable genetic modification of neural stem cells (NSC) that
      constitutively secrete brain-derived neurotropic factor (BDNF) and to explore the
      biological role on the survival and neurite outgrowth of cultured dorsal root
      ganglion (DRG) neurons. METHODS: BDNF gene fragment from human brain cDNA
      libraries was obtained by using PCR. With molecular cloning technique, the
      recombinant stem cell viral vector with report gene was constructed, which is
      that MSCV-BDNF-IRES(2)-EGFP vector could encode Polycistronic mRNA. Viral
      particle was packaged by PT67 cell line and infected neural stem cells (mouse
      clone: C17.2). After selection with cloning cylinder, the expression of BDNF was
      assessed by immunohistochemistry enzyme linked immunosorbent assay (ELISA) and
      reverse transcriptase polymerase chain reaction (RT-PCR). The effects of stable
      gene-modified neural stem cells on embryonic mouse DRG neurons were evaluated in
      a dual-chambered cocultivation system at 3th, 10th day. RESULTS: RT-PCR analysis
      demonstrated expression of mRNA for human-BDNF. ELISA confirmed the presence of
      secreted BDNF 24 h after transfection and showed that the level of BDNF
      production by NSC-BDNF transfected C17.2 was at a rate of (14.6 +/- 0.8) ng x d(
      1) x 10(-6) cells even after 3 months. With immunohistochemical analysis,
      compared with the control, the longer neurite outgrowth of cultured DRG cells and
      the more survival neurons were observed in NSC-BDNF transfected cells group.
      CONCLUSIONS: BDNF gene could be stably expressed in C17.2 cell line by MSCV, and
      the BDNF gene-modified NSC markedly enhances the survival and neurite outgrowth
      of cultured DRG neurons.

PMID- 16412320
TI  - [Diagnosis, treatment and prevention of postmenopausal osteoporosis].

PMID- 16412321
TI  - [Relationship between the age of menarche, menopause and other factors and
      postmenopause osteoporosis].
AB  - OBJECTIVE: To evaluate the relationship between osteoporosis (OP) and the age of
      menarche and menopause, parity and lactation and bone mineral density (BMD).
      METHODS: BMD was measured in 1472 postmenopausal women by Norland XR-36 dual
      energy X-ray absorptiometry (DXA) from May 1999 to April 2003 in our hospital.
      All data of BMD were compared and statistically analyzed between women with
      different age of menarche and menopause, parity and lactation period. The
      diagnostic criteria of osteoporosis was defined by a loss of BMD greater than 2.5
      standard deviations below average peak BMD of young adult women. RESULTS: In all
      1472 subjects, the incidence of osteoporosis is 58.5% (861/1472). There was
      significant increase in osteoporosis of lumbar spine in women with the age of
      menarche > or = 17 (119 out of 336 cases were with osteoporosis in lumbar)
      compared with women with age of menarche < or = 13 (75 out of 276 cases were with
      osteoporosis in lumbar). In women with menarche age of 11-13, 14-16, 17-19,
      lumbar vertebral (L(2-4)) BMD values were (0.83 +/- 0.16), (0.82 +/- 0.16), (0.80
      +/- 0.14) g/cm(2), respectively. There was significant increase in BMD of lumbar
      in the menarche age group of 11-13 compared with the age group of 17-19 in women
      within menopause 1-10 years (P < 0.05). Among all women aged between 55-65, there
      was significant increase in OP in women with the menopause age < or = 48 compared
      with menopause age > or = 54 (P < 0.01). BMD of the L(2-4), Trochanter, Ward
      triangle was significantly increased in women who had had one delivery or being
      nulliparous compared with women having more than four deliveries; BMD of the L(2
      4), Ward's triangle were significantly increased in women with less than six
      months of lactation compared with those lactating more than thirty-six months.
      CONCLUSIONS: The later the menarche and the earlier the menopause, the higher the
      degree of osteoporosis; the more deliveries and period of lactation, the lower
      the BMD. Age is one of the high risk factors of osteoporosis.

PMID- 16412322
TI  - [Study of bone mineral density in complete androgen insensitivity syndrome
      patients].
AB  - OBJECTIVE: To explore the characteristics and treatment of bone mineral density
      (BMD) change in complete androgen insensitivity syndrome (CAIS) of Chinese
      patients. METHODS: Fourteen cases of CAIS were studied retrospectively through
      analyzing and comparing BMD of pre- and post-orchidectomy with normal Chinese men
      and women. BMD at the lumbar spine and the femur were measured by dual energy X
      ray absorptiometry (DXA). RESULTS: Ten cases of CAIS had pre-orchidectomy DXA, in
      which 6 cases had very significantly reduced L(2-4) BMD (0.92 +/- 0.08) g/cm(2)
      compared with normal men and women (P < 0.01). Five cases had significantly
      reduced femur neck BMD (0.89 +/- 0.12) g/cm(2) compared with normal male (P <
      0.05). Seven cases had 12 post-orchidectomy DXA, in which all L(2-4) BMD (0.95 +/
      0.06) g/cm(2) were very significantly reduced compared with normal male and
      female (P < 0.01), femur neck BMD (0.91 +/- 0.08) g/cm(2) was also significantly
      reduced compared with normal male (P < 0.01) and normal female (P < 0.05).
      CONCLUSIONS: There are different degrees of osteopenia in patients of CAIS,
      especially in lumbar vertebra. This suggests that estrogen and androgen play
      important roles in the acquirement and maintenance of bone mass.

PMID- 16412323
TI  - [Study of the impact of candidate genes on bone mineral density in postmenopausal
      women].
AB  - OBJECTIVE: To investigate the impact of multiple candidate genes on bone mineral
      density in postmenopausal women. METHODS: Bone mineral density (BMD) at lumbar
      spine and femoral neck were measured by dual-energy X-ray absorptiometry (DEXA)
      in 205 postmenopausal women. Polymerase chain reaction (PCR) and direct
      sequencing technique were used to identify osteoprotegerin gene polymorphism.
      Parathyroid hormone, calcitonin receptor, osteocalcin and leptin receptor genes
      were evaluated through PCR and restriction fragment length polymorphism. Leptin
      gene was genotyped by PCR and agarose electrophoresis. RESULTS: One G-1181C
      single nucleotide polymorphism was found in the first exon of the osteoprotegerin
      gene. After adjustment for age and body mass index, women who were with the CC
      genotype of osteoprotegerin gene or the bb genotype of parathyroid hormone gene
      had the highest BMD value at the lumbar spine, which was (1.042 +/- 0.142)
      g/cm(2) and (1.196 +/- 0.133) g/cm(2), respectively. No association was found
      among calcitonin receptor, osteocalcin, leptin and leptin receptor genes with BMD
      in postmenopausal women. Multivariate regression analysis found that the
      osteoprotegerin, parathyroid hormone and osteocalcin genes associated with the
      variance of BMD at the lumbar spine, and the parathyroid gene associated with the
      variance of BMD at the femoral neck. CONCLUSIONS: There is some association
      between osteoprotegerin, parathyroid hormone genes and BMD in postmenopausal
      women. However, no relationship has been found among calcitonin receptor,
      osteocalcin, leptin and leptin receptor genes with BMD in postmenopausal women.
      The osteoprotegerin gene may be the useful genetic marker for osteopenia in
      postmenopausal women.

PMID- 16412324
TI  - [Study on the relation between concentration of circulating non-host fetal DNA in
      pregnant women and pre-eclampsia].
AB  - OBJECTIVE: To explore the diagnostic value of plasma fetal DNA level in
      preeclampsia. METHODS: Thirty cases of pregnant women with preeclampsia (at 33
      weeks and 3 days) and 30 cases of normal pregnant women (at 34 weeks and 3 days)
      were selected. All the pregnant women carried a male fetus by B-ultrasound, and
      were sampled at gestational 20 weeks, third trimester and at 1 hour, 3 hours, 6
      hours after delivery. SRY levels in maternal blood were quantitated by polymerase
      chain reaction (QF-PCR). The endotheliotoxin (ET) level was measured with RIA.
      RESULTS: (1) Mean fetal DNA level of patients with preeclampsia at 20 weeks of
      gestation was (316 +/- 61) copy/ml. They were (266 +/- 79) copy/ml, (396 +/- 91)
      copy/ml, (165 +/- 43) copy/ml for light and severe preeclampsia women and normal
      pregnant women, respectively. Maternal blood fetal DNA levels in pregnant women
      with preeclampsia at 20-weeks of gestation were significantly higher than those
      normal pregnant women (P < 0.01). (2) Mean fetal DNA level of patients with
      preeclampsia in third trimester was (970 +/- 413) copy/ml. They were (758 +/-
      357) copy/ml, (1285 +/- 573) copy/ml, (319 +/- 99) copy/ml for light and severe
      preeclampsia and normal pregnant women, respectively. Maternal blood fetal DNA
      levels in pregnant women with preeclampsia in third trimester were significantly
      higher than those normal pregnant women (P < 0.01). (3) Maternal blood mean fetal
      DNA level of patients with preeclampsia were (139 +/- 45) copy/ml, (76 +/- 31)
      copy/ml, (44 +/- 13) copy/ml at 1 hour, 3 hours, and 6 hours after delivery,
      respectively. Mean fetal DNA level was (102 +/- 42) copy/ml, (57 +/- 25) copy/ml,
      (36 +/- 12) copy/ml for patients with light preeclampsia, (209 +/- 51) copy/ml,
      (97 +/- 40) copy/ml, (52 +/- 17) copy/ml for patients with severe preeclampsia,
      and (33 +/- 13) copy/ml, (9 +/- 5) copy/ml, 0 copy/ml for normal pregnant women.
      Significant difference was found between preeclampsia and control groups (P <
      0.01). (4) The mean endotheliotoxin level for preeclampsia women was (80 +/- 18)
      ng/L. For light preeclampsia, severe preeclampsia and normal pregnant women ET
      levels were (74 +/- 14) ng/L, (89 +/- 32) ng/L, (50 +/- 11) ng/L, respectively.
      ET levels in pregnant women with preeclampsia were significantly higher than
      those normal pregnant women (P < 0.01). (5) A positive correlation was found
      between fetal DNA levels and ET levels in preeclampsia group (r = 0.748, P <
      0.01). CONCLUSION: The fetal DNA determination may help diagnose preeclampsia.

PMID- 16412326
TI  - [Activity and role of tryptase after entrance of amniotic fluid into blood in
      rats].
AB  - OBJECTIVE: To investigate the activity and role of tryptase after entrance of
      amniotic fluid into blood in rats. METHODS: Thirty female Wistar rats (20 day
      pregnancy) were divided into the control group (10, injected with normal saline),
      amniotic group (10, injected with amniotic fluid), meconium group (10, injected
      with 1% meconium). After injection, pulmonary tissue was taken out. Tryptase
      activity was measured by special substrate. The histology of pulmonary tissue was
      determined by immunohistochemistry (HE). RESULTS: (1) Dropsy, hemorrhage, and
      infiltration of neutrophil (PMN), macrophage, leukomonocyte were observed in two
      experimental groups, but no such changes were found in control group. (2) After
      injection, tryptase activity in meconium group 176.4 +/- 8.6 and amniotic fluid
      group 165.4 +/- 7.4 was significantly higher than preexperimental groups 146.8 +/
      8.9 and 147.8 +/- 9.5, respectively (t = 7.58 and t = 4.64, P < 0.01); tryptase
      activity in control group was 145.3 +/- 10.6 before injection and 146.9 +/- 9.4
      after injection, respectively, there was no difference (t = 0.37, P > 0.05).
      After injection, tryptase activity in meconium and amniotic fluid groups was
      significantly increased than that in control group (F = 30.66, P < 0.05).
      CONCLUSION: The activity of tryptase was significantly increased after entrance
      of amniotic fluid into blood in rats. Degranulation of mast cells to release
      tryptase may be the important cause of the pathophysiologic change after entrance
      of amniotic fluid into blood. These results suggest a role for mast cell
      activation in the mechanism of amniotic fluid embolism. This method is sensitive
      and effective for diagnosis of amniotic fluid embolism in clinic.

PMID- 16412325
TI  - [Preliminary study on prenatal diagnosis from coelomic cells using polymerase
      chain reaction].
AB  - OBJECTIVE: To evaluate the number of cells in coelomic fluid by DNA quantitation
      with picogreen and to establish a new method of prenatal diagnosis for sex-linked
      disorders in early pregnancy. METHODS: Coelomic fluid and chorionic villi were
      obtained from 25 women undergoing planned termination of pregnancy. DNA of
      coelomic fluid was extracted by boiling method and DNA concentration was measured
      with picogreen, and fetal gender was determined by X and Y-sequence-specific PCR.
      The results of PCR were compared with traditional cytogenetic analysis of
      chorionic villi. RESULTS: There were 750-6270 cells in 0.5-3 ml coelomic fluid.
      Two amplified bands of X and Y were identified simultaneously in the coelomic
      fluid of male-fetus. Only one band was detected in that of female-fetus. Eleven
      out of 25 coelomic fluids showed X and Y bands, and the others were one band (X).
      The overall concordance rate of gender determination between coelomic fluid and
      chorionic villi was 100%. CONCLUSION: The number of cells in 0.5-3 ml coelomic
      fluid can completely meet the needs of PCR reactions. Sex determination using
      cells in coelomic fluid and PCR is reliable, which can be used as a prenatal
      diagnostic test for sex-linked disorders and has the advantages of high
      sensitivity and rapidity.

PMID- 16412327
TI  - [Clinical study on laparoscopic technique for vaginoplasty using an ileum with
      long vascular pedicle].
AB  - OBJECTIVE: To study the operative methods and clinical outcome of laparoscopic
      ileal colpopoiesis with long vascular pedicle. METHODS: We reviewed 31 cases
      which had received ileal colpopoiesis, including 25 cases of congenital absence
      of vagina and 6 cases of male-to-female trans-sex. All cases were operated on by
      laparoscopic (8 cases) and laparoscopy assisted (23 cases) ileal colpopoiesis.
      The postoperative results were analyzed through physical examination and
      interview regarding the patient's functional status and satisfaction during
      sexual intercourse. RESULTS: Ileal colpopoiesis were preformed successfully on
      all 31 cases. Follow-ups of 3-13 months were done for all of them. Patients used
      vaginal mould for at least 8 months. All artificial vaginas had excellent
      cosmetic results, including adequate vaginal length, good lubrication, and
      appearance and physical functions similar to female natural vagina, and sexual
      function was reportedly satisfactory. One of the patients had an operative
      complication of an intestinal obstruction, which was cured by a second operation
      and other treatments. CONCLUSIONS: The laparoscopic and laparoscopy assisted
      ileal vaginoplasty is a feasible, safe and ideal method of current vaginoplasty
      due to its minor damage, excellent cosmetic results and similarity to normal
      vaginal features. However, vaginal mould should be used for a long period of time
      (at least 8 months) after an operation, to prevent vaginal orifice shrinkage.

PMID- 16412329
TI  - [Comprehensive staging surgery in treatment of malignant ovarian germ cell
      tumor].
AB  - OBJECTIVE: To evaluate the impact of comprehensive staging surgery on relapse and
      survival of malignant ovarian germ cell tumor (MOGCT). METHODS: The clinical data
      of 127 MOGCT cases treated in Peking Union Medical College Hospital from June
      1980 to June 2003 were analyzed retrospectively. All the data about comprehensive
      staging surgery during primary surgery were collected, and other factors related
      to prognosis were also collected at the same time. COX model was applied in
      multivariate analysis related to relapse and survival. RESULTS: Among 127
      patients, 45 (35.4%) received comprehensive staging surgery. Seventy-one cases
      (55.9%) received satisfied cytoreduction with residual tumor < 2 cm, 11 cases
      (8.7%) with residual tumor > or = 2 cm, and another 45 cases (35.4%) were
      undetermined. Seventy-five cases (59.1%) received cisplatin, etoposide, and
      bleomycin (BEP) or cisplatin, vinblastine, and bleomycin (PVB) chemotherapy, 18
      cases (14.2%) received vincristine, actinomycin D, cyclophosphamide (VAC)
      chemotherapy, and 34 cases (26.8%) received other regimens or no chemotherapy.
      During the follow up period, 7 of 45 patients relapsed in patients who received
      compressive staging surgery, while the latter was not a significant factor (P =
      0.061). Chemotherapy regimen and residual tumor were the significant factors
      related to the relapse (P < 0.05). All the patients were followed up for 2-254
      months. Chemotherapy regimen and residual tumor were also the significant factors
      related to survival (P < 0.05). Compressive staging surgery showed no significant
      effect on survival (P > 0.05). CONCLUSIONS: The critical treatment for MOGCT is
      satisfactory cytoreduction surgery plus standard chemotherapy. Comprehensive
      staging surgery shows no significant impact on the prognosis of MOGCT patients.

PMID- 16412328
TI  - [Gene transfer of tumor necrosis factor related apoptosis inducing ligand to
      endothelial progenitor cell for ovarian cancer therapy].
AB  - OBJECTIVE: To express tumor necrosis factor related apoptosis inducing ligand
      (TRAIL) protein using endothelial progenitor cell (EPC) and observe antitumor
      activity of secreted TRAIL in cell culture supernatant. METHODS: EPC were
      isolated by immunomagnetic sorting. Human TRAIL plasmid was transfected into EPC
      by lipofectamine 2000. The cell culture supernatant was harvested and the
      secreted protein was measured by immunoassay method. Apoptosis rate was analysed
      by flow cytometry. RESULTS: EPC could develop from the culture of cord blood
      CD(133)(+) (cluster of differentiation 133(+)) cells. EPC may be transiently
      transfected with human TRAIL plasmid. The level of TRAIL in the cell culture
      supernatant was higher in the TRAIL transfected group than in the non-transfected
      group and green-fluoro protein (GFP) transfected group (532.8 pg/ml versus 12.4
      and 9.2 pg/ml). Apoptosis detection showed that TRAIL had high antitumor activity
      in 3AO cell, the apoptosis rate of ovarian cancer cell could reach 24.1%.
      CONCLUSIONS: In vitro, TRAIL EPC gene transfer enhances EPC to secrete TRAIL
      protein, and induces apoptosis of ovarian cancer cell. There is a good clinical
      prospect for EPC in the gene therapy of ovarian cancer.

PMID- 16412330
TI  - [Effect of antisense survivin RNA transfection on the growth of ovarian carcinoma
      SKOV3 cells in vitro and in vivo].
AB  - OBJECTIVE: To study the inhibition effect of survivin antisense RNA on the growth
      of ovarian carcinoma SKOV3 cells, and the tumorigenic ability of the transfected
      SKOV3 cells implanted subcutaneously in nude mice. METHODS: The recombinant
      vector pcDNA3-SVVas was constructed by directed cloning of fragments of survivin
      cDNA into the vector. The ovarian carcinoma SKOV3 cells were transfected with
      pcDNA3-SVVas by lipofectamine 2000 (SKOV3/SVVas cells), and blank vector pcDNA3
      as control (SKOV3/neo cells). The effect of survivin antisense RNA on cell growth
      was assessed by growth curve. The inhibition of expression of endogenous survivin
      protein and mRNA was evaluated by immunohistochemical stain and RT-PCR. The
      apoptosis of cells was assessed by flow cytometry. Twenty-four nude mice were
      divided into three groups, then SKOV3/SVVas, SKOV3/neo and SKOV3 cells were
      implanted subcutaneously. The growth of tumor was observed and the tumor volume
      calculated. RESULTS: The expression of survivin significantly decreased in
      SKOV3/SVVas cells in comparison to that in SKOV3 and SKOV3/neo cells. The growth
      of the SKOV3/SVVas cells became significantly slower than those of SKOV3 cells
      and SKOV3/neo cells (P < 0.01). The expression of survivin protein and mRNA in
      the SKOV3/SVVas cells were (37.5 +/- 1.0)% and 0.407 +/- 0.022 respectively,
      compared with SKOV3 [(81.2 +/- 0.4)%, 0.793 +/- 0.042] and SKOV3/neo [(80.4 +/-
      0.8)%, 0.734 +/- 0.039]. The difference was significant (P < 0.01). After
      transfected with pcDNA3-SVVas, cells were found apoptosis in early stage by flow
      cytometry. The apoptosis rate was (27.4 +/- 9.6)%. There was significant
      difference between SKOV3/SVVas cells and SKOV3 cells, as well as between
      SKOV3/SVVas and SKOV3/neo cells (P < 0.05). The tumorigenic ability of
      SKOV3/SVVas cells was reduced. The first time that tumor could be detected in
      SKOV3/SVVas group, (14.0 +/- 1.0) days was significantly prolonged compared to
      SKOV3/neo, (6.1 +/- 0.8) days and SKOV3, (5.8 +/- 0.9) days (P < 0.01). In
      SKOV3/SVVas group, 5 of 8 nude mice were found tumor, the growth rate of tumor
      was slower compared with the other two groups. When compared in volume, the
      difference was significant (P < 0.01). CONCLUSIONS: Stable expression of survivin
      antisense RNA can effectively inhibit the growth of SKOV3 cells and reduce the
      expression of endogenous survivin proteins and mRNA, induce the apoptosis of
      cells. Survivin antisense RNA can inhibit the tumorigenesis of SKOV3 cells in
      nude mice.

PMID- 16412331
TI  - [RNA interference silencing expression of survivin gene and reversing drug
      resistance of ovarian cancer cell line SKOV3/ADM].
AB  - OBJECTIVE: To examine expression of survivin gene in ovarian epithelial carcinoma
      drug resistant cell line SKOV3/ADM and its parental cell line SKOV3, and
      induction of cells apoptosis and reversal of drug resistance in SKOV3/ADM after
      RNA interference (RNAi) silencing survivin gene. METHODS: The transcription of
      survivin gene in cells was detected by semi-quantitative RT-PCR, the protein
      expression level of survivin gene was analyzed by immunofluorescence staining.
      SKOV3/ADM cells were treated with pshRNA-survivin and paclitaxel (Taxol), and
      acridine orange (AO)/ethidium bromide (EB) staining was performed to evaluate the
      apoptosis of cells. RESULTS: Survivin gene mRNA expressed by 99.1% and 75.3%
      respectively in cell lines SKOV3/ADM and SKOV3, while fluorescent cells were 59
      +/- 5 and 42 +/- 3 (P < 0.05). After the introduction of pshRNA-survivin into
      SKOV3/ADM, mRNA transcription level of survivin gene decreased distinctly from
      99.1% to 7.9%. The apoptotic cells of control group detected by AO/EB staining
      was 3.6 +/- 0.6, of Taxol group 10.2 +/- 1.0, of RNAi group 48.5 +/- 4.9, of RNAi
      + Taxol group 71.5 +/- 6.8. Apoptosis ratio between RNAi + Taxol group and RNAi
      group had significant difference (P < 0.05), and that between RNAi + Taxol group
      and Taxol group also had significant difference (P < 0.05). CONCLUSIONS: Both
      survivin gene mRNA and its protein are over-expressed in ovarian epithelial
      carcinoma cell lines SKOV3 and SKOV3/ADM, the level of survivin gene expressed in
      SKOV3/ADM is obviously different compared with that in its parental cell line
      SKOV3. RNA interference targeted against specific sequences of survivin in
      SKOV3/ADM cell could significantly reduce the level of survivin mRNA transcripts
      and protein, effectively induce the cells apoptosis and restore the sensitivity
      of cell to conventional chemotherapeutic agents Taxol.

PMID- 16412345
TI  - [State of arts in therapy of childhood acute lymphoblastic leukemia in China].

PMID- 16412332
TI  - [Application of fertiloscopy in infertile women].
AB  - OBJECTIVE: To investigate the advantages of fertiloscopy in the examination and
      therapy of infertile women. METHODS: One hundred and fifteen infertile patients
      underwent fertiloscopy including transvaginal hydrolaparoscopy (THL),
      conventional dye-test, hysteroscopy, and dye-test using catheterization of the
      tubal ostium by hysteroscopy from May 2003 to Mar 2005. Access to the pouch of
      Douglas was achieved in 110 patients (95.7%). The primary infertile patients
      (primary group) and secondary infertile patients (secondary group) included
      respectively 49 and 61 cases. The patients of tubal occlusion in two groups were
      respectively 21 and 22 cases preoperatively. The fallopian tube patency, pelvic
      adhesions, complete evaluation (all pelvic organs seen) or not, and intra- and
      postoperative complications were observed. RESULTS: There was no significant
      difference in the percentage of uni- and bilateral tubal patency cases between
      two groups postoperatively (69.4%, 34/49 vs 68.9%, 42/61) (P > 0.05). Of the
      cases that were bilateral tubal occlusion in both groups preoperatively, the uni-
      and bilateral tubal patency cases accounted for respectively 47.6% (10/21) and
      50.0% (11/22) (P > 0.05) postoperatively. There was no significant difference in
      the percentage of pelvic adhesions cases between two groups (42.9%, 21/49 vs
      60.7%, 37/61; P > 0.05). The overall complete evaluation rate of pelvic organs
      was 69.1% (76/110), the rates of both groups were respectively 77.6% (38/49) and
      62.3% (38/61, P > 0.05). The rate of additional transabdominal operative
      laparoscopy was 18.2% (20/110) after fertiloscopy, of which, the rate of primary
      group was only 8.2% (4/49), much less than that of secondary group (26.2%, 16/61;
      P < 0.05). Seventeen women underwent transabdominal operative minilaparoscopy
      after fertiloscopy. No complications including pelvic organ injury, rectum
      perforation, intra- and postoperative bleeding, and postoperative pelvic
      inflammation occurred. CONCLUSIONS: THL is simple, convenient, and complication
      free for the infertile women. Fertiloscopy could be used as a first-line and one
      stop procedure in the pelvic assessment of infertile women without clinical or
      ultrasound evidence of pelvic disease instead of transabdominal laparoscopy.
      Transabdominal laparoscopy should be only used as a complementary procedure after
      fertiloscopy.

PMID- 16412347
TI  - [Pain, a problem to which pediatricians have not paid sufficient attention].

PMID- 16412346
TI  - [Comments in diagnosis, treatment and reports for childhood leukemia in China].

PMID- 16412348
TI  - [Analysis of therapeutic effectiveness of Nanfang ALL 99 protocol in childhood
      acute lymphoblastic leukemia patients].
AB  - OBJECTIVE: With more precise diagnostic criteria and risk classifications, more
      effective therapy administered in clinical trials, and better supportive care,
      the outcome of children with acute lymphoblastic leukemia (ALL) has been improved
      dramatically. Today, approximately 80% of children treated for this disease in
      developed countries enjoy long-term event free survival (EFS) and in most
      instances, would be cured. In this study, treatment outcome of 82 childhood ALL
      patients in the hospital were analyzed, and ways for how to improve the EFS rate
      in childhood ALL were explored. METHODS: Eighty-two patients with ALL were
      enrolled into the Nanfang ALL 99 protocol which derived from German BFM ALL 95
      and Hong Kong-Singapore acute lymphoblastic leukemia 97 (HK-SG ALL 97).
      Dexamethasone instead of hydrocortisone was used for triple intrathecal therapy.
      Standard at risk patients who had been irregularly treated in other hospitals for
      short periods of time were classified as at intermediate risk. When ANC was > or
      = 1.0 x 10(9)/L and platelet > or = 100 x 10(9)/L, chemotherapy was started. Life
      table method was used to estimate survival rate and statistical analysis was done
      by using software SPSS for Windows. RESULTS: From March 1999 to September 2003,
      82 childhood ALL patients were treated with the Nanfang ALL 99 protocol and 78
      (95.1%) patients attained complete remission (CR) in a median time of 33 days.
      Out of 82 patients, 13 patients dropped out of the the Nanfang ALL 99 protocol
      because of financial difficulty or other reasons. Sixty nine patients were
      consecutively treated with the Nanfang ALL 99 protocol. The overall EFS rate at 2
      years, 3 years and 5 years were 91.3%, 85.9% and 75.2%, respectively, with a
      median observation duration of 34 months. Three patients died of complications
      (4.3%). The disease relapsed in 6 patients and they died finally. CONCLUSION: The
      outcome of patients treated with the Nanfang ALL 99 protocol was favorable, and
      the mortality rate of this chemotherapeutic protocol was low. This protocol was
      well tolerated by Chinese patients and therefore the protocol is worthy of
      application in China.

PMID- 16412349
TI  - [Experimental study on the mechanism of the apoptosis of leukemic cells induced
      by valproic acid].
AB  - OBJECTIVE: To overcome the drug-resistance of tumor cells is one of the methods
      of improving the therapeutic results. Histone deacetylase inhibitors (HDACIs) is
      a novel class of chemotherapeutic agents which can induce apoptosis of tumor
      cells. Valproic acid (VPA) is a common drug used in the treatment of epilepsy. It
      has been shown that VPA has a marked HDACIs effect at the pharmaceutical level,
      and can induce the differentiation and apoptosis of transformed cells. But the
      mechanism of its effect has not been clarified. The aim of this study was to
      investigate the mechanism of VPA in inducing the apoptosis of leukemic cells at
      molecular level. METHODS: The cell lines U937, Jurkat clone E6 - 1 (Jurkat) and
      BALL-1 were cultured in RPMI 1640 medium containing 20% calf serum, then divided
      into three groups (control group, 1 mmol/L VPA group and 1 mmol/L VPA + 1
      micromol/L Pan-caspase inhibitor zVAD-fmk group). At 72 hours after the
      treatment, the cells were double stained with Aunexin and PI (propidium iodide)
      and then were analyzed with the flow cytometry (FCM) to detect apoptosis. Before
      and after treatment with VPA the mean fluorescence index (MFI) of Bcl-2, Bax, Bcl
      xl and the levels of caspase 8, 9 and 3 were also detected with the FCM. The
      changes of P(44/42) mitogen activating protein kinase (MAPK) and phosphorylated
      P(44/42) MAPK were determined by Western blotting. RESULTS: Seventy-two hours
      after the treatment, 1 mmol/L VPA induced apoptosis of U937 and Jurkat. The
      apoptotic rate of U937 was (75.78 +/- 4.20)% and that of Jurkat was (53.50 +/-
      5.87)% (P < 0.01, vs. control group); zVAD-fmk could fully inhibit the apoptosis
      of U937, and the apoptotic rate was (2.89 +/- 0.36)%; while it could partly
      inhibit the apoptosis of Jurkat, and the apoptotic rate was (15.38 +/- 1.40)% (P
      < 0.01). 1 mmol/L VPA could not induce the apoptosis of BALL-1 which had a high
      expression level of Bcl-2. The MFI of Bcl-2, Bax and Bcl-xl in these three cell
      lines did not change significantly with VPA (P > 0.05). After treatment with VPA,
      the level of caspase 3 in U937 increased from (14.09 +/- 1.19)% to (32.30 +/-
      2.47)%, and caspase 8 from (4.58 +/- 1.41)% to (86.47 +/- 3.26)% (P < 0.01), but
      there was no significant change in caspase 9 [(13.25 +/- 3.11)% and (10.95 +/-
      1.30)%]. In Jurkat, the level of caspase 3 increased from (12.01 +/- 1.63)% to
      (35.56 +/- 0.27)%, and caspase 9 from (13.89 +/- 1.71)% to (75.89 +/- 4.08)% (P <
      0.01 for both); no significant change was observed for caspase 8 [(5.94 +/-
      1.38)% and (5.44 +/- 0.72)%]. In BALL-1, there was a slight decline in caspase 3
      (P < 0.05). With the effect of VPA, levels of P(44/42) MAPK and phosphorylated
      P(44/42) MAPK decreased in all three cell lines (P < 0.01). CONCLUSION: VPA could
      induce apoptosis of U937 through the activation of caspase 3 and 8; and it
      induced the apoptosis of Jurkat involving the activation of caspase 3 and 9.
      P(44/42) MAPK pathway also plays an important role in this course. VPA induced
      apoptosis of these cell lines without the alteration of Bcl-2, Bax and Bcl-xl.
      High level of Bcl-2 could antagonize the effect of VPA.

PMID- 16412350
TI  - [Effects of supernatant of cord blood CD3AK cells on proliferation,
      differentiation and apoptosis of HL-60 cells].
AB  - OBJECTIVE: The study was to investigate the impact of cord blood CD(3)AK cell
      culture supernatant (CS) on proliferation, differentiation and apoptosis of HL-60
      cells. METHODS: HL-60 cells were treated with different concentrations of CS
      (10%, 15%, 20%) for 3 days, 6 days and 9 days, and the same cells of control
      group were not treated with CS. The growth of induced cells was assessed with
      Trypan blue staining and cell counting with cytometer. The differentiation marker
      CD(11b) on the cell surface and cell-cycle was analyzed by flow cytometry (FCM),
      cell morphology (Wright-Giemsa staining) and NBT test to determine the extent of
      differentiation. Meanwhile, the changes of the apoptosis of the cells induced by
      20% CS at different time points (3, 6 and 9 days) were analyzed by TUNNEL-POD,
      and the apoptotic characteristics of cells were observed. RESULTS: The growth of
      HL-60 cell was inhibited as CS-inducing time and the dose of CS increased. At the
      same time, but HL-60 cell number in G(0)/G(1) phase of cell-cycle increased, but
      HL-60 cell number in S phase decreased compared with untreated group. The HL-60
      cells induced by 20% CS for 9 days showed that (52.7 +/- 1.8)% of cells were at
      G(0)+G(1) phase and (43.8 +/- 1.1)% were at S phase (P < 0.05), which
      demonstrated that HL-60 cells induced by 20% CS underwent G(0)/G(1) phase cell
      cycle arrest. The volume of the differentiated cells was enlarged gradually as CS
      inducing time prolonged. After 3 days the differentiating cells began to express
      differentiating marker CD(11b) on the cell surface and the nuclei morphology of
      the differentiated cells was also changed and NBT-stained cells increased in
      number with the increased dose of CS increased. Three days after induction by 20%
      CS, the induced cells began to show signs of apoptosis and the apoptotic
      percentage of induced cells gradually increased with CS-induction time. The rate
      of apoptosis of cells was (33.3 +/- 2.3)% at 9 days (P < 0.01). CONCLUSION: CS
      could not only inhibit the growth of HL-60 cells but also induce the
      differentiation and apoptosis in HL-60 cells.

PMID- 16412351
TI  - [Seroprevalence of antibody against human metapneumovirus in Beijing].
AB  - OBJECTIVE: To understand the seroprevalence of antibody against the newly
      identified human metapneumovirus (hMPV) in Beijing. METHODS: The antigenic
      specificity of hMPV N protein cloned into vector pET30a and then expressed in E
      coli was verified by using SDS-PAGE and Western blotting in 116 serum specimens.
      The plasmid pET30a without insert was used as control. Totally 710 serum
      specimens collected from non-respiratory infection patients visited the
      Outpatient Departments of Children's Hospital affiliated to Capital Institute of
      Pediatrics and Xuanwu Hospital, Beijing from April 1996 to March 1997 were tested
      for specific IgG antibody against hMPV N protein. RESULTS: The bands with
      expected molecular weight showed only on the membranes transferred by the
      expressed hMPV N protein and incubated with rabbit hyperimmune serum against hMPV
      N protein polypeptides as well as the collected human sera, indicating the
      specificity of the expressed hMPV N protein. Out of 710 specimens tested, 17.2%
      (122/710) were positive for antibody to N protein. Antibody positive rate was the
      lowest in 2 to 6 months old infants (3.1%); the rate declined from 13.2% in
      newborns to 6.1% in 1 to 2 months old infants, then to 3.1% in the 2 to 6 months
      group, and sustained at about 3.0% from 6 months group to 30 years of age, then
      increased to 28.1% in 30 to 39-year-old adults, 32.3% in 40 to 49-year-old adults
      and to 38.5% in the group over age of 50 years. CONCLUSION: The expressed hMPV N
      protein is reliable when it was used as antigen for testing specific IgG antibody
      against hMPV in human sera. The high seroprevalence of antibody against hMPV N
      protein and early age antibody acquisition suggest that hMPV has been circulating
      in Beijing and the importance of the virus as pathogen should be further
      analyzed.

PMID- 16412352
TI  - [Level of vitamin K-dependent coagulation factors in premature infants and the
      influence of maternal antenatal administration of vitamin K1 on their activity].
AB  - OBJECTIVE: Infants less than 35 weeks of gestational age are susceptible to peri
      /intraventricular hemorrhage (PIVH). This may be due in part to low
      concentrations of vitamin K-dependent coagulation factors. This study was
      conducted to determine the umbilical cord blood activities of vitamin K-dependent
      coagulation factors II, VII, IX and X in premature infants to understand whether
      preterm infants have absence status of these factors the changes of theses
      factors' activities in premature infants' umbilical blood after vitamin K(1) was
      given to mothers antenatally and the preventing effectiveness of PIVH after
      maternal antenatal supplement of vitamin K(1). METHODS: Pregnant women in preterm
      labor at less than 35 weeks of gestational age were randomly selected to receive
      antenatal vitamin K(1) intramuscular or intravenous injections 10 mg per day for
      2 to 7 days (vitamin K(1) group), or no vitamin K(1) treatment (control group).
      Dexamethone was antenatally given to both groups of pregnant women routinely.
      Vitamin K(1) group had 44 infants and the control group had 133 infants. During
      the same period, thirty full-term neonates' cord blood samples were obtained to
      determine theses factors to compare with those from the premature infants. The
      cranial ultrasound was performed by a same physician to understand whether the
      neonates were complicated with PIVH and its severity. RESULTS: The levels of
      vitamin K-dependent coagulation factors in umbilical blood in control group were
      significantly lower than those in full-term infants' cord blood (P < 0.05).
      However, in vitamin K(1) group, supplement of vitamin K(1) antenatally could
      significantly increase activities of factors II, VII and X in preterm infants'
      cord blood (P < 0.05). The total occurrence rates of PIVH in vitamin K(1) group
      and control group were 31.8% and 52.6%, respectively, (P = 0.017), and the
      frequency of severe PIVH in vitamin K(1) group and control group was 2.3% and
      12.0%, respectively (P = 0.057). CONCLUSION: Preterm infants have absence status
      of vitamin K-dependent coagulation factors. Administration of vitamin K(1) to
      pregnant women at less than 35 weeks of gestational age resulted in significantly
      improved activities of vitamin K-dependent coagulation factors II, VII, and X,
      and a significantly decreased frequency of PIVH and less severe hemorrhage in
      preterm infants.

PMID- 16412353
TI  - [Immunohistochemical study of RET protein in Hirschsprung's disease and allied
      Hirschsprung's disorder].
AB  - OBJECTIVE: Hirschsprung's Disease (HD) and allied Hirschsprung's disorder (HAD)
      have very similar clinical manifestations, but there are many different theories
      about the two diseases. The present study was designed to understand the
      expression of Ret protein in HD and HAD, and to explore the role of Ret protein
      in the pathogenesis of HD and HAD. METHODS: Colon specimens from patients with
      confirmed HD and HAD, including 15 cases of HD (male 12, female 3) and 11 cases
      of HAD (male 8, female 3) were collected for this study. At the same time normal
      colon specimens from 10 individuals with other diseases were used as control. The
      expression of Ret protein in the intestinal tissue was detected by using
      immunohistochemical SABC technique with mouse anti-Ret monoclonal antibody.
      RESULTS: In the colon specimens from normal controls and the dilated segments of
      colon from HD and HAD patients, moderate to large number of Ret-positive cells
      were observed among the ganglion cells of myenteric plexuses and submucosal
      plexuses (P > 0.05). On the contrary, Ret-positive cells were not seen in the
      stenotic segment of colon from HD patients. But there was positive staining in
      the stenotic segment of the colon from HAD. Moreover, giant ganglion cells
      showing strongly positive staining could be seen. There were also displastic
      cells, small cells, and cells with irregular shape. Statistical analysis showed
      significant differences in Ret cells positivity between the stenotic segment of
      colon of HD and the normal control (P < 0.001) as well as between HD and HAD (P <
      0.001). CONCLUSION: Ret protein may play an important role in the pathogenesis of
      HD and could not have definite relationship with HAD.

PMID- 16412355
TI  - [Multiple-factor analysis of weight gain in very low birth weight infants].
AB  - OBJECTIVE: To investigate the correlative factors of weight gain in very low
      birth weight infants (VLBW). METHODS: Fifty-one cases of VLBW from July 1998 to
      March 2004 were analyzed retrospectively. RESULTS: Twenty two cases were small
      for gestational age (SGA) and 29 cases were appropriate for gestational age
      (AGA). The age of first feeding was (2.35 +/- 2.29) d. Caloric intake was (377.61
      +/- 121.50) kJ/(kg.d) [(90.25 +/- 29.04) kcal/(kg.d)] and protein intake was
      (2.18 +/- 0.83) g/(kg.d). The age of birth weight regained was (7.41 +/- 3.57) d
      and the velocity of weight gain was (16.38 +/- 9.29) g/d or (12.63 +/- 7.15)
      g/(kg.d). Single factor analysis found that early feeding and caloric supply and
      protein supply had significant influence on weight gain (P < 0.05). The result of
      multivariate linear analysis showed that the significant risk factors were
      associated with supply of calorie and protein. The equation was Y (weight gain) =
      -6.426 + 0.120X(1) (caloric supply) + 3.737X(2) (protein supply) (P < 0.01). The
      caloric supply of the cases that achieved the nutritional goal was (468.19 +/-
      67.11) kJ/(kg.d), [(111.90 +/- 16.04) kcal/(kg.d)], and that with enteral
      nutrition and partial parenteral nutrition was [(520.62 +/- 21.59) kJ/(kg.d)],
      [(124.43 +/- 5.16) kcal/(kg.d), (451.49 +/- 68.41) kJ/(kg.d)], [(107.98 +/-
      16.35) kcal/(kg.d)] respectively. There was significant difference between the
      two groups (P < 0.05). The mean rank of time of birth weight regaining, the time
      in hospital stay and duration of parenteral nutrition providing at least 75% of
      the total daily fluid volume was 18.58, 20.24 and 20.11 in the group of early
      feeding, and it was 33.00, 32.48 and 31.83 in the group of late feeding,
      respectively. There were significant differences between the two groups (P <
      0.05). CONCLUSION: Sufficient supply of calorie and protein should be ensured in
      VLBW infants, especially in SGA and severely ill infants. It was very important
      to feed VLBW infants as early as possible, which could improve feeding tolerance
      and gastrointestinal maturation. VLBW infants should receive parenteral nutrition
      as supplements to enteral feeding.

PMID- 16412356
TI  - [The mechanisms responsible for the therapeutic effects of anti-Fas ligand
      antibody on viral myocarditis in mice].
AB  - OBJECTIVE: Viral myocarditis (VM) is one of the most common acquired myocardial
      diseases in children. However, its pathogenesis is not clear. Recent studies
      indicate that the cytotoxicity mediated by cytotoxic T lymphocyte (CTL) plays an
      important role in the development of myocardial injury involved in VM. Apoptosis
      mediated by Fas/FasL pathway is an essential mechanism of target cells damage by
      CTL. In this study, the authors investigated the regulatory effects of
      neutralizing anti-Fas ligand (anti-FasL) antibody on apoptosis and caspase-3
      expression in experimental coxsackievirus B3 myocarditis and the role of the CTL
      mediated apoptosis in myocardium through Fas/FasL pathway in the development of
      VM. METHODS: A total of 80 BALB/c mice were used in the experiments. They were
      divided randomly into the following groups: normal control group (Gr1), CVB3
      control group (Gr2), IgG control group (Gr3) and anti-FasL antibody therapy group
      (Gr4). The mice in Gr2, Gr3 and Gr4 were inoculated with 0.15 ml of TCID(50)
      10(9)/ml coxsackie virus B3 (CVB3) and the mice in Gr1 with 0.15 ml of Eagle
      reagent. The mice in Gr3 and Gr4 were inoculated with IgG (0.1 mg/kg) and FasL
      antibody (0.1 mg/kg) on days 0 and days 3 after inoculation (p.i.), respectively.
      Eight mice in each group were sacrificed on day 10 p.i. Histopathological studies
      and terminal transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays
      were used to quantify inflammation, necrosis and apoptosis in myocardium. The
      expression of active caspase-3 in myocardium was determined by
      immunohistochemistry. Caspase-3 mRNA and CVB3 mRNA were analyzed by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Caspase-3
      activation and apoptosis were seen in the myocardium of mice with myocarditis.
      They had a significantly positive correlation with the changes of myocardial
      histopathologic scores (r = 0.81, P < 0.05; r = 0.73, P < 0.05). (2) The
      pathologic scores, average percentages of apoptotic cardiomyocytes, expression of
      active caspase-3 (protein and mRNA) and expression of CVB3 mRNA in myocardium of
      mice in Gr4, were significantly reduced compared to those in the myocardium of
      mice in Gr2 (P < 0.01, P < 0.01, P < 0.01, P < 0.01, and P < 0.05, respectively)
      and Gr3 (P < 0.01, P < 0.01, P < 0.05, P < 0.01, and P < 0.05, respectively).
      CONCLUSION: Myocytic apoptosis is a key mechanism responsible for myocardial
      damage in viral myocarditis. Anti-FasL antibody can effectively reduce expression
      of active caspase-3 protein and mRNA, viral replication, cardiomyocytic apoptosis
      and myocardial injury in the experimental CVB3 myocarditis.

PMID- 16412357
TI  - [Effects of glutamine on alpha-sarcomeric actin and its mRNA expression of
      myocardium in rats with endotoxemia].
AB  - OBJECTIVE: Endotoxemia is a serious syndrome resulting in multi-organ failure.
      Once it happens, the penetration of small intestine epithelium increases, body
      liquid losses, then effective circulating blood decreases and serious metabolic
      acidosis, serious hypotension, systolic failure, and even shock may occur. In
      this pathological process, endotoxin, tumor necrosis alpha and systolic
      dysfunction play important roles. Nowadays, many studies have been done to
      resolve the systolic dysfunction, but too much attention had been paid to the
      followings: the depressions of myocardium caused by tumor necrosis alpha, other
      inflammatory factors, endotoxin and metabolic acidosis; the disturbance of blood
      vessel-nerve regulations; nitric oxide (NO)/inducible nitric oxide synthase
      (iNOS) over-synthesis and the decreased density of beta-receptors in the
      myocardium and/or their activities. Little attention has been paid to the
      relationship between alpha sarcmeric actin (alpha-SA) and systolic dysfunction
      during endotoxemia. Glutamine (Gln) can be metabolized into glutathione, an
      eliminator of free radical. It has been used in preventing myocardial damage from
      reperfusion. This study aimed to observe the dynamic changes of alpha-SA and mRNA
      expressions in rats with endotoxemia and examine the effects of Gln on them.
      METHODS: Classical rat model of endotoxemia was established by intraperitoneal
      injection of LPS (4 mg/kg, Escherichia coli O55:B5, Sigma). 121 Wistar 18-day
      rats were divided into three groups randomly, (1) 0 h control group (normal
      saline: 1 ml/kg, n = 11). (2) LPS group (LPS: 4 mg/kg, n = 55). (3) Gln group
      (LPS: 4 mg/kg and immediately 13.64%; Gln: 1 ml/kg, Fresenus, n = 55),
      Furthermore, LPS and Gln groups were divided into 2, 4, 6, 24 and 72 h time
      points (n = 11). Each time point of LPS and Gln as well as control rats were
      anaesthetized at each time point with 1% chloral hydrate injected
      intraperitoneally at the dosage of 1 ml/kg. Then rats were sacrificed at appoint
      time, and the hearts were isolated. Eight of them were put in 76 degrees C liquid
      nitrogen and then frozen in minute 80 degrees C icebox in order to measure the
      expression of alpha-SA mRNA by RT-PCR. Three of them were fixed in 4%
      formaldehydum polymerisatum for 12 to 16 h, then the expression of alpha-SA was
      detected by immunohistochemistry. RESULTS: (1) Compared to 0 h, the expressions
      of alpha-SA and mRNA in LPS group were significantly depressed (P < 0.01). In LPS
      group, the lowest was at 6 - 24 h, while in Gln group, it was postponed to 24 h.
      At 72 h, there was no difference in expressions of alpha-SA between Gln and 0 h
      group (P > 0.05). (2) Comparing at same time point, the expressions of alpha-SA
      were significant higher in Gln group than those in LPS group, while the
      expressions of alpha-SA mRNA in Gln group were high at 4-72 h. There was,
      however, no significant difference at early phase (P > 0.05). CONCLUSION: Alpha
      SA and its mRNA expression were depressed in LPS-induced endotoxemia, especially
      from 6 to 24 h. It could damage the systolic function. alpha-SA decrease in
      endotoxemia was due to the inhibited synthesis other than the promoted
      degradation. Glutamine could inhibit the effects of LPS on both alpha-SA and its
      mRNA expressions.

PMID- 16412358
TI  - [Pathological changes of brain at different maturational stages caused by
      pentylenetetrazol-induced repeated seizure in rat models].
AB  - OBJECTIVE: To observe the histopathological changes in rat hippocampus at
      different maturational stages after repeated kindled seizures, and to explore
      their underlying epileptogenesis processes. METHODS: Three groups of Wistar rats
      (postnatal days: P10, P20, P60) were given pentylenetetrazol (PTZ)
      intraperitoneal injection for 5 days to induce repeated kindled seizures, and the
      age-matched rats in control group were injected with normal saline. The
      behavioral changes, the morphology and the neurons counting in hippocampus, as
      well as the expression of NF-kappaB were observed. RESULTS: (1) In the three
      groups, the latency of seizure and the latency of IV/V grade were significantly
      lower in the rats of group P10 and P20 [(1.2 +/- 0.6) min and (14.4 +/- 2.3) min
      vs. (4.7 +/- 1.6) min and (24.5 +/- 4.5) min] than group P60 [(8.6 +/- 2.0) min
      and (41.9 +/- 4.5) min], whereas the duration of convulsion in group P10 and P20
      [(46.2 +/- 4.8) min and (29.8 +/- 5.9) min] was longer than those of group P60
      [(17.1 +/- 5.0) min]. (2) The neuron counting of CA(1), CA(3) and hilar in the
      P10 and P20 groups showed no differences as compared to their controls, whereas
      adult rats (P60) had a significant neuron loss in CA(1) and CA(3) pyramidal
      cells, compared with the control group [(6.3 +/- 1.5)/250 microm(2), (3.6 +/-
      1.4)/250 microm(2) vs. (8.2 +/- 1.9)/250 microm(2), (5.6 +/- 1.7)/250 microm(2)].
      However, the dentate granule cells in immature rats (P10) with daily seizures had
      a significant increase as compared with the controls [(23.3 +/- 3.1)/250
      microm(2) vs. (16.3 +/- 1.6)/250 microm(2)]. (3) Prominent sprouting was seen in
      the CA(3) stratum pyramidal layer in all experimental rats with 5 daily seizures,
      regardless of the age. But the degree of sprouting had significant differences
      among the experimental groups (P < 0.05). (4) NF-kappaB was expressed
      significantly in CA(3), CA(1) and dentate granule cells 24 hours after PTZ
      kindling when compared with the control groups, with the spectral density
      decreased with age. CONCLUSION: (1) There were great differences in the
      vulnerability to the repeated seizure-induced brain damage at different
      maturational stages in rats. The immature brain appeared to be less vulnerable to
      the repeated seizures. (2) There was less hippocampus neuron loss and milder
      mossy fiber sprouting after repeated seizures in the developing rats than mature
      ones, which may be a pathological evidence underlying the prospect that the
      immature brain was more resistant to the seizure-induced neuronal injury. (3) The
      high expression of NF-kappaB may exert a certain biological effects in the
      seizure-induced neuronal injury.

PMID- 16412359
TI  - [Cardiac troponin I is increased after interventional closure of congenital heart
      diseases in children].

PMID- 16412360
TI  - [Vascular necrosis of femoral head in childhood lymphocytic malignant tumor].

PMID- 16412361
TI  - [Clinical analysis of 10 patients with hemophagocytic syndrome].

PMID- 16412362
TI  - [Analysis of prognosis-related factors in pediatric myelodysplastic syndrome].

PMID- 16412363
TI  - [Prediction of early mental and behavior disorders by S-100b protein expression
      analysis in children with enterovirus encephalitis].

PMID- 16412364
TI  - [Report of two compatriot brothers with congenital dyserythropoietic anemia].

PMID- 16412365
TI  - [A case of Beckwith-Wiedemann syndrome].

PMID- 16412366
TI  - [Bronchial arteriography for the diagnosis of massive hemoptysis uncontrolled by
      medication: report of 2 cases].

PMID- 16412367
TI  - [Viral myocarditis presented as pseudo-myocardial infarction, a case report].

PMID- 16412368
TI  - [Successful treatment of Kasabach-Merrit syndrome with pingyangmycin lipiodol
      emulsion arterial embolization].

PMID- 16412369
TI  - [Misdiagnosis of congenital hypothyroidism caused overhydration, a case report].

PMID- 16412370
TI  - [The characteristics and requests of the clinical psychology test for children].

PMID- 16412371
TI  - [Advance of study on molecular cytogenetics and clinical application in acute
      leukemia].

PMID- 16412372
TI  - [Research progress on congenital muscular dystrophy].

PMID- 16412373
TI  - Distribution and circumstances of injuries in squatter settlements of Karachi,
      Pakistan.
AB  - OBJECTIVES: This research was conducted to study incidence, distribution, type,
      causes, severity and circumstances of injuries among people living in squatter
      settlements in Karachi, Pakistan. METHODS: Trained interviewers sought a 2 weeks
      recall for minor injuries for which no health care was sought, 2 months recall
      for major injuries for which a health provider was consulted and 1 year recall
      for hospitalization, disability and death from every third household in five
      squatter settlements in Karachi between May and August 1995. For understanding
      the injury circumstances 250 in-depth interviews of the injured or the close
      relatives were also conducted. RESULTS: Among 1182 households, having 9891
      residents, 84 minor, 42 major injury episodes, 7 hospitalizations, 0.6 permanent
      disabilities and 0.3 deaths per 1000 person years were reported. Including all
      injury episodes, the common types of injury were cutting or piercing (n = 532),
      falls (n = 382) and burns (n = 235) estimating to 54, 38 and 23 injury episodes
      per 1000 person years. Injury mainly resulted from a piece of glass (n = 367),
      falling from height (n = 98) and knife (n = 97) estimating to 37, 10 and 10
      injury episodes per 1000 person years, respectively. Fall (n = 32, 3.2/1000
      person years) was the major reason for hospitalizations and all permanent
      disabilities resulted from closed injuries. Medically trained providers were
      mostly contacted (n = 339, 34/1000 person years), but traditional healers were
      preferred in bone injury. CONCLUSION: Injuries are a major cause of morbidity and
      mortality in Pakistan and the national health and development agenda should
      include assessment and prevention of injuries.

PMID- 16412374
TI  - Towards single-molecule DNA sequencing: assays with low nonspecific adsorption.
AB  - New DNA sequencing techniques are currently being developed using single-molecule
      fluorescence-based detection of enzymatic double-strand synthesis. Such
      application requires surface architectures on which single-stranded templates can
      be immobilized. A further important attribute is a very low tendency to attract
      fluorescently labeled bases nonspecifically. On this account, the adsorption
      behaviour of Cy5-dNTPs on a variety of surface coatings was studied by performing
      real-time measurements of the DNA synthesis using a supercritical angle
      fluorescence biosensor. It is demonstrated that polyacrylic acid coatings are an
      excellent choice to minimize the nonspecific binding of the bases.

PMID- 16412375
TI  - Spectrophotometric determination of caffeine and theophylline in pure alkaloids
      and its application in pharmaceutical formulations.
AB  - A novel-coupling reagent is used for the simple and sensitive spectrophotometric
      determination of caffeine (CF) and theophylline (TP) in pure or pharmaceutical
      formulations. The method is based on the oxidation of CF and TP with sodium
      metaperiodate in the presence of acetic acid, followed by coupling with 3-methyl
      2-benzo thiazolinone hydrazone hydrochloride (MBTH), to produce a blue-colored
      product with a lambda(max) of 630 nm. The method is reproducible and has been
      applied for the determination of CF and TP in the tablets. The results are
      comparable to those obtained with the British pharmacopoeia (BP) method. Common
      excipients used as additives in pharmaceutical preparations do not interfere in
      the proposed method.

PMID- 16412376
TI  - [Pre-peritoneal continuous infusion of local anesthetics for pain relief after
      laparotomy. A preliminary report].
AB  - INTRODUCTION: Continuous administration of local anesthetic through a catheter
      placed in the scar of a laparotomy is a postoperative analgesic technique, which
      seems effective but remains little developed and poorly codified. METHODS: In
      this prospective evaluation, we present a series of 25 observations of adult
      patients scheduled for abdominal laparotomy, to which a multiperforate catheter
      was placed at the end of the intervention by the surgeon in pre-peritoneal
      position, allowing the continuous perfusion of ropivacaine over the first 48
      postoperative hours. Patients received intravenous paracetamol associated with
      ketoprophene or nefopam. Opiates were given as rescue analgesics, in case of
      failure in pain relief, defined on objective criteria measured on visual analogic
      scale (VAS). RESULTS: The feasibility of the technique was excellent, except in
      one case of catheter obstruction. Pain was adequately relieved, with a majority
      of patients having VAS scores lower than 3/10 cm with the VAS, as well as rest as
      during mobilization. Only 9 patients needed morphine rescue analgesics. There was
      no sign of clinical overdose nor parietal complication related to the technique.
      Blood dosages of ropivacaine, carried out among 5 patients having received 600 mg
      daily, showed serum concentrations below the thresholds of toxicity. CONCLUSIONS:
      These results reveal a good effectiveness of the method, with moderate pain
      intensity and a low analgesic consumption. The local and general tolerance was
      excellent.

PMID- 16412377
TI  - Effect of aqueous extract from Neem (Azadirachta indica A. Juss) on
      hydrophobicity, biofilm formation and adhesion in composite resin by Candida
      albicans.
AB  - OBJECTIVE: Azadirachta indica, a Meliaceae family tree, has been used in India
      for many years in the treatment of several diseases in medicine and dentistry.
      Current research analyses the effects of the leaf aqueous extract from
      Azadirachta indica (Neem) on the adhesion, cell surface hydrophobicity and
      biofilm formation, which may affect the colonisation by Candida albicans.
      METHODS: Azadirachta indica extract was tested in vitro on strains of Candida
      albicans 12A and 156B. Changes in hydrophobicity were reported in assays of yeast
      adhesion to hydrocarbons, in biofilm formation with glucose and in the adhesion
      of the microorganisms on light cured composite resin. Assays involved enumeration
      of candidal colony-forming units together with scintillation counting of
      radiolabelled Candida and compared to a solution of chlorhexidine digluconate
      0.125% widely used in dentistry. RESULTS: Yeast growth in Neem extract was not
      inhibited in concentrations ranging from 0.1mg/ml. A statistically significant
      increase (p<0.05) in cell surface hydrophobicity was evident for the two strain
      tested and there was also an associated increase in biofilm formation after
      contact with Neem extract in concentration 0.01 g/ml. Decrease in adhesion
      capacity of cells to composite resin was also recorded. CONCLUSION: An anti
      adhesive mechanism of action by Azadirachta indica is proposed based on the
      results observed.

PMID- 16412378
TI  - Identification of citrullinated eukaryotic translation initiation factor 4G1 as
      novel autoantigen in rheumatoid arthritis.
AB  - Antibodies against citrullinated proteins are highly specific for rheumatoid
      arthritis. We previously reported that functional variants of the gene encoding
      peptidylarginine deiminase type 4 were closely associated with RA. The purpose of
      this study was to investigate the citrullinated autoantigens recognized by serum
      samples from patients with RA. The human chondrocyte cDNA expression library was
      citrullinated by PADI4 and was immunoscreened with anti-modified citrulline
      antibodies and sera from patients with rheumatoid arthritis. One immunoreactive
      cDNA clone containing a 2480-base pair insert was isolated and sequence analysis
      revealed that the cDNA included a part of the eukaryotic translation initiation
      factor 4G1. Immunoreactivity against a recombinant citrullinated eIF4G1 fragment
      was observed with high specificity in 50.0% of RA patients. The levels of
      antibodies against citrullinated eIF4G1 were correlated with those of anti-CCP
      antibodies. Citrullinated eIF4G1 was identified as a candidate citrullinated
      autoantigen in RA patients. Citrullination of eIF4G1 may thus be involved in the
      pathogenesis of RA.

PMID- 16412379
TI  - Gene expression profile in the heart of spontaneous dwarf rat: in vivo effects of
      growth hormone.
AB  - Excess and deficit of growth hormone (GH) both affect cardiac architecture as
      well as its function. To date, experimental and clinical studies have reported
      that GH has an inotropic effect on animal and human heart, however, it remains
      controversial whether GH is applicable to the treatment for the patients with
      chronic heart failure. Also, the mechanism by which GH exerts these biological
      effects on the heart is not well understood. In this study, we attempted to
      specify the genes regulated by GH in the heart of spontaneous dwarf rat using a
      microarray analysis. We found that soluble forms of guanylate cyclase, cofilin1,
      and thymosin beta4 mRNA were up-regulated in the heart by GH treatment. On the
      other hand, acyl-CoA synthetase, aldosterone receptor, myosin regulatory light
      chain, troponin T, laminA, and beta-actin mRNA were down-regulated. These results
      suggest GH regulates essential molecules that regulate structural, contractile,
      remodeling, and regenerative functions. Collectively, our data indicate a new
      integrative understanding for the biological effects of GH on cardiac function.

PMID- 16412380
TI  - Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen
      receptor-positive breast cancer.
AB  - The non-receptor tyrosine kinases c-Src and focal adhesion kinase (Fak) mediate
      signal transduction pathways that regulate cell proliferation, survival,
      invasion, and metastasis. Here, we investigated whether c-Src and Fak are
      activated during progression of hormone-dependent breast cancer. Maximally active
      c-Src was overexpressed in a subset of tamoxifen-resistant variants and in
      metastases of recurrent hormone-treated breast cancer. Active Fak was also
      frequently observed in these tumors. We also show that estrogen receptor (ER) can
      bind to Fak and that estrogen can modulate Fak autophosphorylation supporting a
      cross-talk between these two pathways. Inhibition of c-Src activity blocked
      proliferation of all tamoxifen-resistant variants, suggesting that inhibitors of
      c-Src-Fak activity may delay or prevent progression and metastasis of ER-positive
      tumors. These studies also raise the possibility that fully active forms of c-Src
      and Fak in breast tumors may be biomarkers to predict tamoxifen resistance and/or
      risk of recurrence in ER-positive breast cancer.

PMID- 16412382
TI  - Dopamine neurons derived from embryonic stem cells efficiently induce behavioral
      recovery in a Parkinsonian rat model.
AB  - To test the in vivo effect of a high yield of dopaminergic (DA) neurons (90% of
      total neurons) which had been generated from a genetically modified mouse
      embryonic stem cell line, N2, the cells were transplanted into a rat model of
      Parkinson's disease (PD). The PD animals grafted with N2-derived cells showed
      significant behavior improvements compared with sham controls from 2 weeks
      posttransplantation, whereas animals with naive D3-derived cells ( approximately
      28% DA neurons of total neurons) showed only a modest recovery. Furthermore,
      hyperactivity observed in the subthalamic nucleus, pedunculopontine nucleus, and
      substantia nigra pars reticulata of PD rat models was dramatically reduced by the
      grafting of N2-derived cells. The number of DA neurons in the striatum which
      originated from N2 grafting was much higher compared to that from D3 grafting,
      and the neurons efficiently released DA in the brain, showing a good correlation
      with behavioral recovery.

PMID- 16412381
TI  - IGF-I-induced VEGF expression in HUVEC involves phosphorylation and inhibition of
      poly(ADP-ribose)polymerase.
AB  - Insulin-like growth factor-I (IGF-I) has been shown to promote angiogenesis by
      enhancing vascular endothelial growth factor (VEGF) expression. However, how IGF
      I-induces VEGF expression is not yet fully understood. With this investigation,
      we propose a new possible mechanism involving downregulation of poly(ADP
      ribosyl)ation (pADPR). We first demonstrated that IGF-I increased VEGF protein
      expression in endothelial cells. Inhibitors of mitogen activated kinase (PD
      98059), phosphatidyl-3-inositol-kinase (LY 294002), and protein kinase C
      (staurosporine) diminished the IGF-I effect suggesting the involvement of signal
      transduction. Since there is an established link between pADPR and
      transcriptional activity, we focused on a possible role of poly(ADP
      ribose)polymerase (PARP). The inhibition of PARP by 3-aminobenzamide or
      nicotinamide enhanced VEGF expression. Additionally, IGF-I markedly decreased
      PARP activity. Furthermore, the IGF-I-mediated inhibition of PARP could be
      demonstrated as a result of protein phosphorylation since phosphorylation of PARP
      decreased its activity in vitro and IGF-I treatment of endothelial cells induced
      PARP phosphorylation. The IGF-I-mediated phosphorylation and inhibition of PARP
      represent a novel mechanism of VEGF protein expression.

PMID- 16412383
TI  - High glucose protects single beating adult cardiomyocytes against hypoxia.
AB  - In the heart, the opening of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels
      seems to be crucial for the cardiac protection against hypoxia/ischaemia. In the
      present study, we have exposed cardiomyocytes under hypoxia to high extracellular
      glucose (30 mM). Under these conditions, intracellular concentration of 1,3
      bisphosphoglycerate has increased confirming stimulation of glycolysis.
      Perforated patch-clamp electrophysiology revealed that hypoxia induces whole-cell
      K(+) current in cardiomyocytes more efficiently in the presence than in the
      absence of high glucose. Glucose significantly promoted survival of
      cardiomyocytes exposed to hypoxia. HMR 1098, an antagonist of sarcolemmal K(ATP)
      channels, inhibited glucose-induced activation of whole-cell K(+) current during
      hypoxia as well as glucose-mediated cytoprotection. An inhibitor of
      glyceraldehyde 3-phosphate dehydrogenase, iodoacetate, inhibited glycolysis in
      hypoxia and blocked the activation of sarcolemmal K(ATP) channels. Based on the
      obtained results, we conclude that the activation of sarcolemmal K(ATP) channels
      is involved in glucose-mediated cardioprotection.

PMID- 16412385
TI  - Characterization of the two catalytic domains in histone deacetylase 6.
AB  - Histone deacetylase 6 (HDAC6) is the only known HDAC with two potentially
      functional catalytic domains, yet the role towards substrate played by these two
      domains remains ambiguous. Most studies report HDAC6 activities measured using
      either immune complexes or in vitro translated products. Here, we characterize
      the activity of highly purified recombinant HDAC6, mutants with active site
      histidine mutations in each domain (H216A and H611A), and individual catalytic
      domains. The deacetylase activities of these proteins, as well as their kinetic
      parameters, were measured using histone, alpha-tubulin, and fluorogenic
      acetylated lysine as substrates. Mutant H216A only slightly lowers the catalytic
      rate. However, mutant H611A decreases the catalytic rate more than 5000-fold. The
      first domain expressed alone is not catalytically active. In contrast, the second
      domain shows only a modest decrease in substrate binding and product formation
      rate. Our results indicate that the in vitro deacetylase activity of HDAC6
      resides in the C-terminal second catalytic domain.

PMID- 16412384
TI  - Regulation of superoxide stress in Pseudomonas putida KT2440 is different from
      the SoxR paradigm in Escherichia coli.
AB  - In Escherichia coli, the SoxR regulon orchestrates genes for defense against
      certain types of oxidative stress through the SoxR-regulated synthesis of the
      SoxS transcription activator. The Pseudomonas putida genome did not reveal a
      clear soxS homolog. The P. putida SoxR protein appears to be functional: its
      expression in an E. coli DeltasoxR strain restored the paraquat inducibility of
      soxS. Of nine candidate P. putida oxidative stress genes, which are known to be
      SoxR regulon in E. coli, tested for response to superoxide or nitric oxide, fumC
      1, sodA, zwf-1, and particularly fpr, encoding ferredoxin:NADP(+) reductase, were
      induced, all independent of P. putida soxR. Disruption of the fpr and finR, a
      regulatory protein that is required for paraquat-dependent expression of the fpr,
      resulted in more oxidative stress sensitivity. However, a P. putida soxR-deletion
      strain had normal resistance to the superoxide-generating agent paraquat. The
      data presented here show that the genetic responses to superoxide stress in P.
      putida differ markedly from those seen in E. coli and Salmonella, and the role of
      P. putida soxR remains to be established.

PMID- 16412386
TI  - Involvement of intestinal alkaline phosphatase in serum apolipoprotein B-48 level
      and its association with ABO and secretor blood group types.
AB  - Serum levels of intestinal alkaline phosphatase (IAP), a protein implicated in
      transcellular transport of chylomicrons, vary among ABO blood groups. In rat
      enterocytes, IAP is associated with chylomicron secretion, but the rat expresses
      only blood group A. It is not known whether chylomicron secretion may be affected
      in humans who express multiple blood group types. Serum samples from 40 healthy
      subjects were obtained after overnight fast and 3h after a high-fat meal, and
      assayed for IAP and apolipoprotein B-48 (apoB-48), both proteins exclusive to
      intestine, although only apoB-48 is found in chylomicrons. The two proteins were
      greater in subjects without blood antigen A (B and O) than in those with this
      antigen (A and AB); 2.4- and 4.7-fold for IAP and 1.5- and 2.0-fold for apoB-48
      before and after the meal, respectively. Moreover, IAP and apoB-48 levels were
      strongly correlated in the subjects with the secretor phenotype (r > 0.81). These
      results indicate that IAP is strongly involved in chylomicron formation and fatty
      acid metabolism might change among ABO blood type. In addition, ABO blood type
      classification in apoB-48 measurement would improve the diagnostic value in the
      evaluation of metabolic syndrome.

PMID- 16412387
TI  - A role of kinase inactive ZAP-70 in altered peptide ligand stimulated T cell
      activation.
AB  - T cell activation signals induced by altered peptide ligands (APLs) are different
      from those induced by the original agonistic peptide. The characteristics of the
      former are partial phosphorylation of TCR-zeta and no tyrosine-phosphorylation of
      zeta-associated protein-70 (ZAP-70). To analyze further those signaling pathways,
      we introduced a dominant negative (DN) form of ZAP-70 into a human CD4(+) T cell
      clone in which fully and partially agonistic peptide ligands have been well
      characterized. We found that some over-expressed partially agonistic ligands
      (OPALs) induced T cell responses without tyrosine-phosphorylation and kinase
      activation of ZAP-70. However, those responses were inhibited in T cells
      expressing DN ZAP-70, which could associate with partially phosphorylated TCR
      zeta. In OPAL-stimulated T cells, PLC-gamma1 was phosphorylated and it was
      suppressed by DN ZAP-70 expression, suggesting that the ZAP-70-TCR-zeta
      association mediates the activation of PLC-gamma1 leading to T cell responses
      even in the absence of kinase activation of ZAP-70.

PMID- 16412388
TI  - Recruitment of clathrin onto endosomes by the Tom1-Tollip complex.
AB  - Tom1 (target of Myb 1) and its related proteins (Tom1L1/Srcasm and Tom1L2)
      constitute a protein family and share an N-terminal VHS (Vps27p/Hrs/Stam) domain
      and a following GAT (GGA and Tom1) domain, both of which are also conserved in
      the GGA family proteins. However, the C-terminal half is not significantly
      conserved between the Tom1 and GGA families or even between Tom1 and Tom1L1. We
      have previously shown that the GAT domain of Tom1 interacts with Tollip (Toll
      interacting protein), which is associated with endosomes, to which it recruits
      Tom1. We here extend the previous data and show that the GAT domains of Tom1L1
      and Tom1L2 also interact with Tollip, and the C-terminal regions of all the Tom1
      family proteins interact with clathrin. Furthermore, when coexpressed with
      Tollip, all the Tom1 family proteins recruite clathrin onto endosomes. These
      results indicate that, in conjunction with Tollip, Tom1 family proteins play an
      important role in recruiting clathrin onto endosomes and suggest that they
      modulate endosomal functions.

PMID- 16412389
TI  - Ghitm is an ortholog of the Bombyx mori prothoracic gland-derived receptor (Pgdr)
      that is ubiquitously expressed in mammalian cells and requires an N-terminal
      signal sequence for expression.
AB  - In a previous paper, we reported the cloning of a cDNA encoding a putative
      receptor, Pgdr, from the prothoracic gland of the silkworm, Bombyx mori. Few
      studies concerning the orthologous cDNA of Pgdr in mammals, a growth hormone
      inducible transmembrane protein (Ghitm) that encodes a putative receptor, have
      been performed. Analysis of the distribution of Ghitm expression revealed
      ubiquitous expression in mouse embryo and adult tissues, as well as mammalian
      cell lines. The pattern of Ghitm expression suggested that once Ghitm mRNA was
      expressed in the putative brain region of mouse embryo, Ghitm-expressing cells
      spread ubiquitously throughout all tissues during embryonic development. In
      addition, Western blot analyses demonstrated that cleavage of the N-terminal
      portion in GHITM appears to regulate the expression level, suggesting that
      cleavage is essential for the proper expression of GHITM.

PMID- 16412390
TI  - The complex formation of PKCdelta through its C1- and C2-like regions in H2O2
      stimulated cells.
AB  - PKCdelta was revealed to make a homologous protein complex that shows a high
      protein kinase activity upon H(2)O(2) stimulation by expressing the enzymes
      having different epitope tags in COS-7 cells. The association of the endogenous
      PKCdelta in the cells was observed by sucrose density gradients. Analysis using
      the mutant replacing the tyrosine phosphorylation sites showed that PKCdelta is
      activated without tyrosine phosphorylation in the stimulated cells, and the time
      course of the activation was parallel with that of the complex formation. The
      binding sites were identified as the C1 and C2-like regions in the regulatory
      domain using a series of deletion mutants. The binding between the C1 and C2-like
      region fragments was induced by cell stimulation, whereas the association of the
      C1 region fragments by itself and that of the C2-like region fragments were
      observed even without stimulation. These results suggest that the protein
      complexes of PKCdelta through the association between the C1 and C2-like regions
      by different combinations are generated in the H(2)O(2)-treated cells, that may
      show an enhanced protein kinase activity.

PMID- 16412391
TI  - Do neonatal bilateral ibotenic acid lesions of the hippocampal formation or of
      the amygdala impair HPA axis responsiveness and regulation in infant rhesus
      macaques (Macaca mulatta)?
AB  - In response to stressful events, the HPA axis is activated triggering the
      successive release of CRF, ACTH, and glucocorticoids. The glucocorticoids in turn
      provide a negative feedback signal to terminate the stress response. The amygdala
      and the hippocampus are involved in the regulation of the HPA axis. In rodents,
      their respective roles have been identified; the amygdala exerts a stimulatory
      effect, whereas the hippocampus provides negative feedback control. In primates,
      however, their regulatory roles are still not well defined. The present study
      compared HPA axis responsiveness and regulation in 3- to 5-month-old rhesus
      macaques that received neonatal (15 +/- 3 days old) bilateral ibotenic acid
      lesions of the hippocampus or amygdala, or sham lesions. Group differences in
      plasma cortisol response to separation from the mother and relocation in a novel
      environment were assessed as well as response to dexamethasone suppression and
      ACTH challenge. Results revealed that the initial cortisol levels after
      separation/relocation did not differ between groups. Subjects with hippocampus
      lesions did not show a suppression of cortisol in response to dexamethasone,
      suggesting a loss of negative feedback control of HPA regulation. Subjects with
      amygdala and sham lesions did not differ in response to dexamethasone. Indeed,
      bilateral neonatal lesions of the amygdala have little impact on HPA axis
      responsiveness and regulation in contrast to lesions in adult monkeys. Finally,
      females displayed higher cortisol levels than males, independently of their
      lesion, indicating that the development of sex differences in the regulation of
      the HPA axis does not involve the amygdala or hippocampus.

PMID- 16412392
TI  - Adenosine treatment delays postischemic hippocampal CA1 loss after cardiac arrest
      and resuscitation in rats.
AB  - Resuscitation from cardiac arrest results in reperfusion injury that leads to
      increased postresuscitation mortality and delayed neuronal death. One of the many
      consequences of resuscitation from cardiac arrest is a derangement of energy
      metabolism and the loss of adenylates, impairing the tissue's ability to regain
      proper energy balance. In this study, we investigated the effects of adenosine
      (ADO) on the recovery of the brain from 12 min of ischemia using a rat model of
      cardiac arrest and resuscitation. Compared to the untreated group, treatment with
      adenosine (7.2 mg/kg) initiated immediately after resuscitation increased the
      proportion of rats surviving to 4 days and significantly delayed hippocampal CA1
      neuronal loss. Brain blood flow was increased significantly in the adenosine
      treated rats 1 h after cardiac arrest and resuscitation. Adenosine-treated rats
      exhibited less edema in cortex, brainstem and hippocampus during the first 48 h
      of recovery. Adenosine treatment significantly lowered brain temperature during
      recovery, and a part of the neuroprotective effects of adenosine treatment could
      be ascribed to adenosine-induced hypothermia. With this dose, adenosine may have
      a delayed transient effect on the restoration of the adenylate pool (AXP = ATP +
      ADP + AMP) 24 h after cardiac arrest and resuscitation. Our findings suggested
      that improved postischemic brain blood flow and ADO-induced hypothermia, rather
      than adenylate supplementation, may be the two major contributors to the
      neuroprotective effects of adenosine following cardiac arrest and resuscitation.
      Although adenosine did not prevent eventual CA1 neuronal loss in the long term,
      it did delay neuronal loss and promoted long-term survival. Thus, adenosine or
      specific agonists of adenosine receptors should be evaluated as adjuncts to
      broaden the window of opportunity in the treatment of the reperfusion injury
      following cardiac arrest and resuscitation.

PMID- 16412393
TI  - Stimulation of cyclic AMP formation and nerve electrical activity by octopamine
      in the terminal abdominal ganglion of the female gypsy moth Lymantria dispar.
AB  - The biogenic amine octopamine is known to be present in the abdominal ganglia of
      some insects, but the expression of functional octopamine receptors in these
      neuronal structures has not yet been characterized. In the present study, we
      describe the presence in the female gypsy moth terminal abdominal ganglion (TAG),
      a key structure in the control of the insect reproductive behavior, of an
      octopamine receptor coupled to stimulation of adenylyl cyclase through the GTP
      binding protein G(s). The rank order of potency of different antagonists, which
      discriminate between the different classes of octopamine receptors, indicated the
      involvement of the neuronal type 3 receptor. The octopamine-stimulated adenylyl
      cyclase activity was inhibited by Ca(2+) in the low micromolar range and by
      activation of either protein kinase A or protein kinase C. In the isolated TAG,
      bath application of octopamine caused an increase of the spontaneous bursting
      activity of the emerging nerve of the 5th pair (V), whereas the antagonist
      mianserin reduced the nerve spiking activity and blocked the stimulatory effect
      of octopamine. These data demonstrate that the gypsy moth TAG expresses
      functional octopamine receptors, which may participate in the neuronal control of
      the insect reproductive behavior.

PMID- 16412394
TI  - Activation of cat SII cortex by flutter stimulation of contralateral vs.
      ipsilateral forepaws.
AB  - A distinguishing feature of SII cortex is that it receives substantial input from
      skin mechanoreceptors located on both sides of the body. It remains uncertain,
      however, if integration of bilateral inputs occurs mainly in those regions of SII
      that represent near-midline body regions or also occurs to a significant extent
      in those regions of SII that represent the distal extremities. This issue was
      addressed using extracellular microelectrode recordings in cat SII in combination
      with the method of optical intrinsic signal (OIS) imaging. Stimulation of the
      central pad of either the contra- or ipsilateral forepaw with a 25-Hz sinusoidal
      vertical skin displacement ("skin flutter") stimulus evoked a prominent OIS
      response ("activation") in an extensive anteroposterior sector of SII. In the
      anteriorly located SII region that yielded the maximal OIS response to
      stimulation of the contralateral central pad, neurons consistently possessed
      receptive fields that included the stimulated skin site. This "forepaw" SII
      region also exhibited significant although 75% weaker OIS activation in response
      to stimulation of the ipsilateral central pad. Stimulation of the central pads of
      either contra- or ipsilateral forepaws also evoked OIS activation in the
      posteriorly located 'hindlimb' region of SII--defined as the SII region comprised
      of neurons with receptive fields on the contralateral hindlimb. The OIS response
      to ipsilateral central pad stimulation was strongest in the posterior SII region
      that borders the suprasylvian fringe--a region in which neurons have very large,
      and frequently bilateral, cutaneous receptive fields. The results indicate that
      widespread regions within cat SII receive cutaneous inputs from the ipsilateral
      distal forelimb. It is suggested that the functional role of these ipsilateral
      inputs may be different in different SII regions.

PMID- 16412395
TI  - Arterial hypotension triggers perifocal depolarizations and aggravates secondary
      damage in focal brain injury.
AB  - Perifocal depolarizations (PFD) have been observed after traumatic brain injury,
      are known to disturb cerebrovascular reactivity and thus may contribute to the
      morphological consequences of brain injury. In this investigation, the role of
      PFD was studied in focal brain lesions with/without induction of delayed
      hypotension. Cerebral freeze lesions were induced in anesthetized normotensive
      rats that underwent perfusion fixation of brains 5 min, 4 h or 24 h after
      lesioning, respectively, to obtain quantitative histopathology. In additional
      groups, a 45-min period of moderate hypobaric hypotension was applied 15 min post
      trauma and brains were perfusion fixed after 4 h or 24 h. In a second series, the
      direct current (DC) potential and cortical laser-Doppler flow (LDF) were measured
      adjacent to lesions under normotensive or hypotensive conditions. Sham procedures
      were carried out in rats that underwent hypotension alone. Lesioning resulted in
      a significant LDF decrease to 50% of baseline, further decreased during
      hypotension to less than 40% of control (P < 0.05). Sham animals had LDF values
      between 60 and 70% of control when subjected to hypotension. Focal brain injury
      always induced a negative DC shift shortly after lesioning. In 6 of 8 rats that
      underwent cold lesion plus hypotension, a second PFD was observed approximately
      2.5 min after onset of hypotension accompanied by a relative LDF increase by 25
      +/- 12%. Lesion expansion was significantly worsened by hypotension (8.19 +/-
      0.56 mm(3) at 24 h) compared with normotensive rats (7.01 +/- 0.3 mm(3) at 24 h,
      P < 0.01). We conclude that hypotension triggers depolarizations by an ischemic
      mechanism that contributes to final tissue damage.

PMID- 16412396
TI  - Daily rhythmicity of large-conductance Ca2+ -activated K+ currents in
      suprachiasmatic nucleus neurons.
AB  - Neurons within the suprachiasmatic nucleus (SCN) comprise the master circadian
      pacemaker in mammals. These neurons exhibit circadian rhythms in spontaneous
      action potential frequency and in the transcription of core circadian clock
      genes, including Period1 (Per1). Targeted electrophysiological recordings from
      SCN neurons marked with a green fluorescent protein (GFP) reporter of Per1 gene
      transcription have previously indicated that K(+) currents are critically
      involved in the expression of neurophysiological rhythmicity. The present study
      examined the role of large conductance, Ca(2+)-activated K(+) channels (BK) in
      the daily rhythmicity of mouse SCN neurons. BK-mediated currents were examined in
      Per1::GFP neurons under voltage clamp using iberiotoxin, a specific BK channel
      blocker. BK current was a greater proportion of whole-cell outward currents
      during the night than during the day. Analysis of iberiotoxin difference currents
      also demonstrated that BK current amplitude and density were greater during the
      night and that the day/night difference in steady state amplitude was not due to
      altered inactivation. Single cell RT-PCR demonstrated the presence of the BK
      channel transcript, KCNMA1, in Per1-expressing neurons. In situ hybridization
      analysis further showed that KCNMA1 mRNA was rhythmically expressed in the SCN
      under light:dark (LD) conditions, peaking during the middle of the night phase.
      Acute inhibition of BK currents blunted the circadian rhythm SCN neuron spike
      frequency. These results establish that BK channel function is elevated at night,
      thus altering SCN neuron activity.

PMID- 16412397
TI  - The Survivin-mediated radioresistant phenotype of glioblastomas is regulated by
      RhoA and inhibited by the green tea polyphenol (-)-epigallocatechin-3-gallate.
AB  - INTRODUCTION: Glioblastoma multiforme's (GBM) aggressiveness is potentiated in
      radioresistant tumor cells. The combination of radiotherapy and chemotherapy has
      been envisioned as a therapeutic approach for GBM. The goal of this study is to
      determine if epigallocatechin-3-gallate (EGCg), a green tea-derived anti-cancer
      molecule, can modulate GBMs' response to ionizing radiation (IR) and whether this
      involves mediators of intracellular signaling and inhibitors of apoptosis
      proteins. MATERIAL AND METHODS: U-87 human GBM cells were cultured and
      transfected with cDNAs encoding for Survivin, RhoA or Caveolin-1. Mock and
      transfected cells were irradiated at sublethal single doses. Cell proliferation
      was analyzed by nuclear cell counting. Apoptosis was detected using a
      fluorometric caspase-3 assay. Analysis of protein expression was accomplished by
      Western immunoblotting. RESULTS: IR (10 Gy) reduced control U-87 cell
      proliferation by 40% through a caspase-independent mechanism. The overexpression
      of Survivin induced a cytoprotective effect against IR, while the overexpression
      of RhoA conferred a cytosensitizing effect upon IR. Control U-87 cells pretreated
      with EGCg exhibited a dose-dependent decrease in their proliferation rate. The
      growth inhibitory effect of EGCg was not antagonized by overexpressed Survivin.
      However, Survivin -transfected cells pretreated with EGCg became sensitive to IR,
      and their RhoA expression was downregulated. A potential therapeutic effect of
      EGCg targeting the prosurvival intracellular pathways of cancer cells is
      suggested to act synergistically with IR. CONCLUSION: The radioresistance of GBM
      is possibly mediated by a mechanism dependent on Survivin in conjunction with
      RhoA. The combination of natural anti-cancerous molecules such as EGCg with
      radiotherapy could improve the efficacy of IR treatments.

PMID- 16412398
TI  - Altered expression of K+ -Cl- cotransporters affects fast paired-pulse inhibition
      during GABA receptor activation in the gerbil hippocampus.
AB  - K+ -Cl- cotransporter (KCC) plays an important role in maintaining neuronal
      activity. However, the effect of seizure activity or pharmacological manipulation
      of GABAergic transmission on KCC expression remains to be clarified. Therefore,
      the present study was performed to investigate whether seizure activity or GABA
      receptor agonist treatment changes KCC expression in the gerbil hippocampus.
      Furthermore, the effect of blockade of KCC on inhibitory transmission in the
      dentate gyrus was identified following applications of GABA receptor agonists.
      The distribution of KCC immunoreactivity in the hippocampus was similarly
      detected between seizure-resistant (SR) and seizure-sensitive (SS) gerbils.
      Baclofen (a GABAB receptor agonist) treatment markedly increased KCC expression
      in the gerbil hippocampus. Baclofen treatment significantly reduced paired-pulse
      inhibition in the dentate gyrus. Furosemide (a KCC inhibitor) treatment amplified
      the effect of baclofen on paired-pulse responses. In contrast, muscimol (a GABAA
      receptor agonist) treatment reduced KCC expression. Enhanced paired-pulse
      inhibition by muscimol treatment was not affected by furosemide treatment. These
      findings suggest that seizure activity in the gerbil may not affect KCC
      expression in the hippocampus. In addition, altered KCC immunoreactivity induced
      by baclofen or muscimol may play an important role in maintaining or regulating
      inhibitory transmission during GABA receptor activation.

PMID- 16412399
TI  - Ischemia-related changes of glial-derived neurotrophic factor and
      phosphatidylinositol 3-kinase in the hippocampus: their possible correlation in
      astrocytes.
AB  - In the present study, we observed the changes of endogenous expression of glial
      cell-line-derived neurotrophic factor (GDNF) and phosphatidylinositol 3-kinase
      (PI-3 kinase) in the gerbil hippocampus after transient forebrain ischemia and
      investigated the correlation between GDNF and PI-3 kinase in the ischemic
      hippocampus. In the sham-operated group, GDNF and PI-3 kinase immunoreactivity
      was not found in any cells in the hippocampal CA1 region. GDNF, not PI-3 kinase,
      immunoreactivity was expressed in non-pyramidal cells in the CA1 region at 6 h
      after ischemic insult. At 12-24 h after ischemia, GDNF and PI-3 kinase
      immunoreactivity in the CA1 region was similar to that of the sham-operated
      group. From 2 days after ischemic insult, GDNF- and PI-3-kinase-immunoreactive
      astrocytes were detected in the CA1 region, and GDNF and PI-3 kinase
      immunoreactivity in astrocytes was highest in the CA1 region 4 days after
      ischemic insult. Moreover, at this time point, GDNF and PI-3 kinase were co
      localized in some astrocytes. Western blotting showed that ischemia-related
      changes of GDNF and PI-3 kinase protein levels were similar to the
      immunohistochemical changes after ischemia. These results suggest that GDNF and
      PI-3 kinase may be related to delayed neuronal death and that GDNF and PI-3
      kinase may be involved in activation of astrocytes.

PMID- 16412400
TI  - Controversies regarding hormone therapy: Insights from inflammation and
      hemostasis.
AB  - Many observational studies and experimental and animal studies have demonstrated
      that estrogen therapy (ET) or hormone therapy (HT) significantly reduces the risk
      of coronary heart disease. Nonetheless, recent randomized controlled trials and
      the Nurses' Health Study in secondary prevention demonstrate trends toward an
      increased risk of cardiovascular events rather than a reduction of risk from HT.
      HT has both anti-inflammatory and pro-inflammatory effects, and it activates
      coagulation and improves fibrinolysis. These effects depend on the route of
      administration, doses of estrogen, age of women, and the presence of coronary
      artery disease or the coexistence of other risk factors for hypercoagulability.
      In this review, we discuss effects of HT on markers of inflammation, hemostasis,
      and fibrinolysis that may link endothelial dysfunction in cardiovascular
      diseases. We also briefly discuss effects of lower doses of HT and tibolone in
      postmenopausal women.

PMID- 16412401
TI  - OxLDL enhances L-type Ca2+ currents via lysophosphatidylcholine-induced
      mitochondrial reactive oxygen species (ROS) production.
AB  - OBJECTIVE: To examine the mechanisms underlying oxidised LDL- (oxLDL)-induced
      alterations in Ca(2+) currents, an effect which underlies altered vascular
      contractility and cardiac myocyte function. METHODS: Ca(2+) currents (I(Ca)) were
      recorded by whole-cell patch-clamp in HEK293 cells expressing L-type Ca(2+)
      channel alpha(1C) subunits or isolated rat ventricular myocytes. oxLDL (but not
      native LDL) significantly enhanced recombinant I(Ca), an effect mimicked by 1
      microM lysophosphatidylcholine (LPC). LPC failed to enhance I(Ca) either in
      mitochondrial electron transport chain-depleted rho(0) cells, or in the presence
      of rotenone (1 microM), or MPP(+) (10 microM). The LPC response was similarly
      ablated by ascorbate (200 microM) or TROLOX (500 microM) and by the mitochondria
      targeted antioxidant, MitoQ (250 nM). In myocytes, enhancement of I(Ca) due to
      LPC was similarly abrogated with rotenone and MitoQ. These data suggest that LPC
      enhanced recombinant Ca(2+) currents due to increased mitochondrial ROS
      production. In support with this, LPC enhanced fluorescence in HEK293 cells and
      cardiac myocytes loaded with a ROS-sensitive mitochondrial dye, reduced
      mitotracker red. CONCLUSION: LPC up-regulates L-type Ca(2+) currents due to
      altered mitochondrial ROS production, an effect which mediates the response of
      the native I(Ca) in cardiac myocytes to oxLDL.

PMID- 16412402
TI  - 17beta-estradiol increases volume, apical surface and elasticity of human
      endothelium mediated by Na+/H+ exchange.
AB  - OBJECTIVE: 17beta-estradiol is known to delay the onset of atherosclerosis in
      women but cellular mechanisms are still unclear. Estrogens bind to specific
      receptors and initiate a signaling cascade that involves the activation of plasma
      membrane Na(+)/H(+) exchange. We hypothesized that estrogens interfere with ion
      transport across the plasma membrane and thus control endothelial structure and
      function. Therefore, we investigated the effects of the sex steroids 17beta
      estradiol, progesterone, and testosterone on volume, apical surface and
      elasticity in human endothelium. METHODS: The atomic force microscope was used as
      an imaging tool and as an elasticity sensor. We applied the antiestrogen
      tamoxifen, the Na(+)/H(+) exchange blocker cariporide and the epithelial
      Na(+)channel blocker amiloride to elucidate the role of transmembrane ion
      transport in hormone-treated human umbilical vein endothelial cells (HUVEC).
      RESULTS: Incubation with 17beta-estradiol for 72 h led to a dose-dependent
      increase of endothelial cell volume (41%), apical cell surface (22%), and cell
      elasticity (53%) as compared to non-17beta-estradiol treated controls. Block of
      the 17beta-estradiol receptor by tamoxifen and of plasma membrane Na(+)/H(+)
      exchange by cariporide prevented the hormone-induced changes. Progesterone and
      testosterone were ineffective. CONCLUSIONS: 17beta-estradiol increases HUVEC
      water content and HUVEC elasticity mediated by activated estrogen receptors. The
      estrogen response depends on the activation of plasma membrane Na(+)/H(+)
      exchange. The increase in endothelial cell elasticity could be one of the
      vasoprotective mechanisms postulated for 17beta-estradiol.

PMID- 16412403
TI  - Caveolae and caveolin in transmembrane signaling: Implications for human disease.
AB  - The identification of various signaling molecules found within caveolae and their
      functional interaction with the integral membrane protein caveolin, a major
      structural component of caveolae, suggests that these membrane microdomains
      participate in transmembrane signaling. Several lines of evidence indicate that
      caveolin may act as a scaffolding protein by direct interaction with and
      modulation of the activity of multiple signaling molecules. The compartmentation
      of various signaling molecules in caveolae and their direct and functional
      interaction with caveolin provides a paradigm by which these membrane
      microdomains are involved in regulating signal transduction pathways. By
      dysregulation of these signal transduction pathways caveolins may be involved in
      the pathogenesis of various diseases. This review focuses on the implications as
      well as controversies of the contribution of caveolae and caveolins for several
      human diseases and the potential implications to therapeutic strategies.

PMID- 16412404
TI  - Soluble guanylate cyclase (sGC) down-regulation by abnormal extracellular matrix
      proteins as a novel mechanism in vascular dysfunction: Implications in metabolic
      syndrome.

PMID- 16412405
TI  - Effects of fumonisins on liver and kidney sphinganine and the sphinganine to
      sphingosine ratio during chronic exposure in ducks.
AB  - Sa and the Sa/So ratio are very sensitive biomarkers of exposure to fumonisins in
      several species. We previously demonstrated that increases in Sa and in the Sa/So
      ratio in serum were less pronounced when ducks ingested fumonisins for more than
      7 weeks than when animals were exposed for only 1-2 weeks [S.T. Tran, D. Tardieu,
      A. Auvergne, J.D. Bailly, R. Babile, S. Durand, G. Benard, P. Guerre, Serum
      sphinganine and the sphinganine to sphingosine ratio as biomarker of dietary
      fumonisins during chronic exposure in ducks, Chem. Biol. Interact., in press].
      The aim of this study was to investigate the kinetics of Sa and of the Sa/So in
      both liver and kidney of ducks that have been previously tested for Sa and the
      Sa/So ratio in serum. Analysis were performed on treatment days 0, 7, 14, 28 and
      77 in five groups of ducks fed fumonisins obtained from an extract of Fusarium
      verticillioides culture material by daily gavage to obtain an exposure equal to
      0, 2, 8, 32 and 128 mg FB1/kg feed. Sa and the Sa/So ratio in tissues were then
      correlated with Sa and the Sa/So ratio previously obtained in serum. The amounts
      on sphinganine 1-phosphate (Sa1P) and sphingosine1-phosphate (So1P) in the liver
      were also investigated. On day 7 of treatment, 2mg/kg FB1 in the feed were
      sufficient to increase Sa and the Sa/So ratio in liver (by 165 and 148%,
      respectively) and kidney (by 193 and 104%, respectively). At a rate of 128 mg/kg
      FB1 in the feed, a very high increase in Sa concentration was observed in both
      liver and kidney without mortality and/or signs of necrosis (respective increase
      of 2034 and 3768%). Although the precise mechanism of the resistance of ducks to
      fumonisin-induced hepatotoxicity is still uncertain, it might be linked to the
      rate at which the sphingoid bases sphinganine and sphingosine are converted to
      their 1-phosphate or other metabolite and eliminated from target tissues.

PMID- 16412406
TI  - Exogenous leptin improves insulin sensitivity in ethanol fed insulin resistant
      mice.

PMID- 16412407
TI  - Molecular diagnostics of genetic eye diseases.
AB  - Eye diseases can be simple or complex, and mostly of heterogeneous molecular
      genetics. Some eye diseases are caused by mutations in a single gene, but some
      diseases, such as primary open angle glaucoma, can be due to sequence variations
      in multiple genes. In some diseases, both genetic and epigenetic mechanisms are
      involved, as was recently revealed in the mechanism of retinoblastoma. Disease
      causative mutations and phenotypes may vary by ethnicity and geography. To date,
      more than a hundred candidate genes for eye diseases are known, although less
      than 20 have definite disease-causing mutations. The three common genetic eye
      diseases, primary open angle glaucoma, age-related macular degeneration, and
      retinitis pigmentosa, all have known gene mutations, but these account for only a
      portion of the patients. While the search for eye disease genes and mutations
      still goes on, known mutations have been utilized for diagnosis. Genetic markers
      for pre-symptomatic and pre-natal diagnosis are available for specific diseases
      such as primary open angle glaucoma and retinoblastoma. This paper reviews the
      molecular basis of common genetic eye diseases and the available genetic markers
      for clinical diagnosis. Difficulties and challenges in molecular investigation of
      some eye diseases are discussed. Establishment of ethnic-specific disease
      databases that contain both clinical and genetic information for identification
      of genetic markers with diagnostic, prognostic, or pharmacological value is
      strongly advocated.

PMID- 16412408
TI  - Patients with congenital hypothyroidism demonstrate different altered expression
      of plasma fibrinogen and haptoglobin polypeptide chains.
AB  - OBJECTIVES: To compare the plasma protein profiles of treated and untreated
      congenital hypothyroidism (CH) patients with those of normal control infants.
      DESIGN AND METHODS: Plasma samples were subjected to two-dimensional gel
      electrophoresis and silver staining or lectin detection. Resolved protein spots
      were analyzed by using computerized densitometry software. RESULTS: The
      significant enhanced expression of the fibrinogen gamma-chain and reduced
      expression of haptoglobin beta-chain were demonstrated in the profiles of
      untreated CH patients using both silver staining and lectin detection methods.
      Lectin detection resolved only a single cluster of the haptoglobin beta-chain for
      the untreated patients, in contrast to five isoform clusters detected in the
      controls' and treated CH patients' profiles. CONCLUSIONS: Plasma from untreated
      CH patients demonstrated different altered expression of fibrinogen and
      haptoglobin polypeptide chains, which was normalized when patients were treated.
      Our data also suggest differences in structures of the N-glycans of haptoglobin
      beta-chain of the untreated CH patients.

PMID- 16412409
TI  - The development of mental state attributions in women with X-monosomy, and the
      role of monoamine oxidase B in the sociocognitive phenotype.
AB  - We hypothesized that women with Turner syndrome (45,X) with a single X-chromosome
      inherited from their mother may show mentalizing deficits compared to women of
      normal karyotype with two X-chromosomes (46,X). Simple geometrical animation
      events (two triangles moving with apparent intention in relation to each other)
      which usually elicit mental-state descriptions in normally developing people, did
      not do so to the same extent in women with Turner syndrome. We then investigated
      the potential role in this deficit played by monoamine oxidase B enzymatic
      activity. MAO-B activity reflects central serotonergic activity, and by
      implication the functional integrity of neural circuits implicated in
      mentalizing. Platelet MAO-B was substantially reduced in Turner syndrome.
      However, contrary to prediction, in this (relatively small) sample there was no
      association between MAO-B enzymatic activity and mentalizing skills in
      participants with and without Turner syndrome.

PMID- 16412410
TI  - Varieties of musical experience.
AB  - In this paper, we argue that music cognition involves the use of acoustic and
      auditory codes to evoke a variety of conscious experiences. The variety of
      domains that are encompassed by music is so diverse that it is unclear whether a
      single domain of structure or experience is defining. Music is best understood as
      a form of communication in which formal codes (acoustic patterns and their
      auditory representations) are employed to elicit a variety of conscious
      experiences. After proposing our theoretical perspective we offer three prominent
      examples of conscious experiences elicited by the code of music: the recognition
      of structure itself, affect, and the experience of motion.

PMID- 16412411
TI  - The biology and evolution of music: a comparative perspective.
AB  - Studies of the biology of music (as of language) are highly interdisciplinary and
      demand the integration of diverse strands of evidence. In this paper, I present a
      comparative perspective on the biology and evolution of music, stressing the
      value of comparisons both with human language, and with those animal
      communication systems traditionally termed "song". A comparison of the "design
      features" of music with those of language reveals substantial overlap, along with
      some important differences. Most of these differences appear to stem from
      semantic, rather than structural, factors, suggesting a shared formal core of
      music and language. I next review various animal communication systems that
      appear related to human music, either by analogy (bird and whale "song") or
      potential homology (great ape bimanual drumming). A crucial comparative
      distinction is between learned, complex signals (like language, music and
      birdsong) and unlearned signals (like laughter, ape calls, or bird calls). While
      human vocalizations clearly build upon an acoustic and emotional foundation
      shared with other primates and mammals, vocal learning has evolved independently
      in our species since our divergence with chimpanzees. The convergent evolution of
      vocal learning in other species offers a powerful window into psychological and
      neural constraints influencing the evolution of complex signaling systems
      (including both song and speech), while ape drumming presents a fascinating
      potential homology with human instrumental music. I next discuss the
      archeological data relevant to music evolution, concluding on the basis of
      prehistoric bone flutes that instrumental music is at least 40,000 years old, and
      perhaps much older. I end with a brief review of adaptive functions proposed for
      music, concluding that no one selective force (e.g., sexual selection) is
      adequate to explaining all aspects of human music. I suggest that questions about
      the past function of music are unlikely to be answered definitively and are thus
      a poor choice as a research focus for biomusicology. In contrast, a comparative
      approach to music promises rich dividends for our future understanding of the
      biology and evolution of music.

PMID- 16412412
TI  - Are we "experienced listeners"? A review of the musical capacities that do not
      depend on formal musical training.
AB  - The present paper reviews a set of studies designed to investigate different
      aspects of the capacity for processing Western music. This includes perceiving
      the relationships between a theme and its variations, perceiving musical tensions
      and relaxations, generating musical expectancies, integrating local structures in
      large-scale structures, learning new compositional systems and responding to
      music in an emotional (affective) way. The main focus of these studies was to
      evaluate the influence of intensive musical training on these capacities. The
      overall set of data highlights that some musical capacities are acquired through
      exposure to music without the help of explicit training. These capacities reach
      such a degree of sophistication that they enable untrained listeners to respond
      to music as "musically experienced listeners" do.

PMID- 16412413
TI  - Chimpanzees deceive a human competitor by hiding.
AB  - There is little experimental evidence that any non-human species is capable of
      purposefully attempting to manipulate the psychological states of others
      deceptively (e.g., manipulating what another sees). We show here that
      chimpanzees, one of humans' two closest primate relatives, sometimes attempt to
      actively conceal things from others. Specifically, when competing with a human in
      three novel tests, eight chimpanzees, from their first trials, chose to approach
      a contested food item via a route hidden from the human's view (sometimes using a
      circuitous path to do so). These findings not only corroborate previous work
      showing that chimpanzees know what others can and cannot see, but also suggest
      that when competing for food chimpanzees are skillful at manipulating, to their
      own advantage, whether others can or cannot see them.

PMID- 16412414
TI  - Giving the boot to the bootstrap: how not to learn the natural numbers.
AB  - According to one theory about how children learn the concept of natural numbers,
      they first determine that "one", "two", and "three" denote the size of sets
      containing the relevant number of items. They then make the following inductive
      inference (the Bootstrap): The next number word in the counting series denotes
      the size of the sets you get by adding one more object to the sets denoted by the
      previous number word. For example, if "three" refers to the size of sets
      containing three items, then "four" (the next word after "three") must refer to
      the size of sets containing three plus one items. We argue, however, that the
      Bootstrap cannot pick out the natural number sequence from other nonequivalent
      sequences and thus cannot convey to children the concept of the natural numbers.
      This is not just a result of the usual difficulties with induction but is
      specific to the Bootstrap. In order to work properly, the Bootstrap must somehow
      restrict the concept of "next number" in a way that conforms to the structure of
      the natural numbers. But with these restrictions, the Bootstrap is unnecessary.

PMID- 16412416
TI  - The mouse forkhead gene Foxc1 is required for primordial germ cell migration and
      antral follicle development.
AB  - Foxc1 encodes a forkhead/winged helix transcription factor expressed in many
      embryonic tissues. Previous studies have investigated defects in the urogenital
      system of Foxc1 null mutants, but the mechanisms underlying the abnormal
      development of the gonad have not been explored. From earliest stages, the mutant
      ovaries are smaller than normal, with fewer germ cells and disorganized somatic
      issue. No bursa membrane is formed, and the oviduct remains uncoiled. Although
      germ cells are specified correctly, many of them do not migrate to the gonadal
      ridge, remaining trapped in the hindgut. Consequently, the number initially
      reaching the gonad is less than 25% of normal. Once in the ovary, germ cells
      proliferate normally, but the supporting somatic cells are not organized
      correctly. Since mutant embryos die at birth, further development was followed in
      ovaries grafted underneath the kidney capsule of ovariectomized females.
      Transplanted ovaries display normal folliculogenesis up to preantral stages.
      However, no follicles develop beyond early antral stages. Mutant follicles are
      often polyovulatory and have disrupted theca and granulosa cell layers. We
      conclude that alongside its previously known roles in kidney, cardiovascular and
      eye development, Foxc1 has essential functions during at least two stages of
      gonad development-germ cell migration and folliculogenesis.

PMID- 16412415
TI  - Cryopreservation of spermatozoa from wild-born Namibian cheetahs (Acinonyx
      jubatus) and influence of glycerol on cryosurvival.
AB  - Sperm cryopreservation is a valuable tool for the genetic management of ex situ
      populations. This study was conducted to assess: (1) semen characteristics of
      wild-born cheetahs; and (2) the impact of three types of glycerol influence
      (duration of exposure, temperature, and method of addition) on sperm
      cryosensitivity. To evaluate the impact of duration of glycerol exposure,
      spermatozoa were incubated in Test Yolk Buffer (TYB) with 4% glycerol at ambient
      temperature (approximately 22 degrees C) for 15 vs. 60 min before
      cryopreservation. To evaluate the influence of temperature and method of glycerol
      addition, spermatozoa were resuspended at ambient temperature either in TYB with
      0% glycerol followed by addition of 8% glycerol (1:1 v/v; at ambient temperature
      vs. 5 degrees C) or directly in TYB with 4% glycerol. All samples were
      cryopreserved in straws over liquid nitrogen vapor and evaluated for sperm
      motility and acrosomal integrity after thawing. Semen samples (n = 23; n = 13
      males) contained a high proportion (78%) of pleiomorphic spermatozoa. Ejaculates
      also contained a high proportion of acrosome-intact (86%) and motile spermatozoa
      (78%). Immediately after thawing, a significant proportion of spermatozoa
      retained intact acrosomes (range, 48-67%) and motility (range, 40-49%). After
      thawing, incubation in glycerol for 60 min at ambient temperature before freezing
      decreased (p < 0.05) sperm motility and acrosomal integrity at one time-point
      each (pre-centrifugation and post-centrifugation, respectively). However, method
      or temperature of glycerol addition had no (p > 0.05) impact on sperm
      cryosurvival. In summary, (1) wild-born cheetahs produce high proportions of
      pleiomorphic spermatozoa but with a high proportion of intact acrosomes; and (2)
      resuspension in 4% glycerol, followed by exposure for up to 60 min at ambient
      temperature, had minimal effect on sperm motility and acrosomal integrity after
      cryopreservation. Results indicate the feasibility of cryopreserving cheetah
      spermatozoa under field conditions, providing a user-friendly method to capture
      and store gametes to enhance genetic management.

PMID- 16412417
TI  - Rac function in epithelial tube morphogenesis.
AB  - Epithelial cell migration and morphogenesis require dynamic remodeling of the
      actin cytoskeleton and cell-cell adhesion complexes. Numerous studies in cell
      culture and in model organisms have demonstrated the small GTPase Rac to be a
      critical regulator of these processes; however, little is known about Rac
      function in the morphogenic movements that drive epithelial tube formation. Here,
      we use the embryonic salivary glands of Drosophila to understand the role of Rac
      in epithelial tube morphogenesis. We show that inhibition of Rac function, either
      through loss of function mutations or dominant-negative mutations, disrupts
      salivary gland invagination and posterior migration. In contrast, constitutive
      activation of Rac induces motile behavior and subsequent cell death. We further
      show that Rac regulation of salivary gland morphogenesis occurs through
      modulation of cell-cell adhesion mediated by the E-cadherin/beta-catenin complex
      and that shibire, the Drosophila homolog of dynamin, functions downstream of Rac
      in regulating beta-catenin localization during gland morphogenesis. Our results
      demonstrate that regulation of cadherin-based adherens junctions by Rac is
      critical for salivary gland morphogenesis and that this regulation occurs through
      dynamin-mediated endocytosis.

PMID- 16412418
TI  - The effect of beta2-adrenoceptor agonists on phospholipase C (beta1) signalling
      in human airway smooth muscle cells.
AB  - Prolonged use of beta2-adrenoceptor agonists has been associated with asthma
      exacerbation. Recently, phospholipase C-beta1 (PLC-beta1) induction in airway
      smooth muscle was proposed to underlie this phenomenon. We aimed to evaluate this
      mechanism in primary human airway smooth muscle cells. Stimulation of cells (1
      microM isoprenaline or salbutamol for 2-48 h or 10(-9)-10(-4)M for 24 h) had no
      effect on PLC-beta1 gene expression. 1 microM beta2-adrenoceptor agonist
      treatment for 24 h did not alter sodium fluoride Inositol Phosphate (IP)
      responses, however augmented histamine IP responses (P<0.05). Therefore, beta2
      adrenoceptor agonists can augment spasmogen responses in airway smooth muscle but
      not via a G-protein/PLC-beta1 mediated mechanism.

PMID- 16412419
TI  - Heterologous expression of mammalian Plk1 in Drosophila reveals divergence from
      Polo during late mitosis.
AB  - Drosophila Polo kinase is the founder member of a conserved kinase family
      required for multiple stages of mitosis. We assessed the ability of mouse Polo
      like kinase 1 (Plk1) to perform the multiple mitotic functions of Polo kinase, by
      expressing a Plk1-GFP fusion in Drosophila. Consistent with the previously
      reported localization of Polo kinase, Plk1-GFP was strongly localized to
      centrosomes and recruited to the centromeric regions of condensing chromosomes
      during early mitosis. However, in contrast to a functional Polo-GFP fusion, Plk1
      GFP failed to localize to the central spindle midzone in both syncytial embryo
      mitosis and the conventional mitoses of cellularized embryos and S2 cells.
      Moreover, unlike endogenous Polo kinase and Polo-GFP, Plk1-GFP failed to
      associate with the contractile ring. Expression of Plk1-GFP enhanced the
      lethality of hypomorphic polo mutants and disrupted the organization of the
      actinomyosin cytoskeleton in a dominant-negative manner. Taken together, our
      results suggest that endogenous Polo kinase has specific roles in regulating
      actinomyosin rearrangements during Drosophila mitoses that its mammalian
      counterpart, Plk1, cannot fulfill. Consistent with this hypothesis, we observed
      defects in the cortical recruitment of myosin and myosin regulatory light chain
      in Polo deficient cells.

PMID- 16412420
TI  - PML-associated repressor of transcription (PAROT), a novel KRAB-zinc finger
      repressor, is regulated through association with PML nuclear bodies.
AB  - Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional
      regulation. Here we identify a novel transcriptional repressor, PML-associated
      repressor of transcription (PAROT), which is regulated in its repressor activity
      through recruitment to PML-NBs. PAROT is a Kruppel-associated box ( KRAB) zinc
      finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a
      linker domain and 8 tandemly repeated C(2)H(2)-ZNF motifs at its carboxy
      terminus. Consistent with its domain structure, when tethered to DNA, PAROT
      represses transcription, and this is partially released by the HDAC inhibitor
      trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1
      (HP1) family and with transcriptional intermediary factor-1beta/KRAB-associated
      protein 1 (TIF-1beta/KAP1), a transcriptional corepressor for the KRAB-ZNF
      family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently
      recruits PAROT and TIF-1beta from heterochromatin to PML-NBs. PML-NB recruitment
      of PAROT partially releases its transcriptional repressor activity, indicating
      that PAROT can be regulated through subnuclear compartmentalization. Taken
      together, our data identify a novel transcriptional repressor and provide
      evidence for its regulation through association with PML-NBs.

PMID- 16412421
TI  - Stroke upregulates TNFalpha transport across the blood-brain barrier.
AB  - To determine how cytokine transport systems at the blood-brain barrier (BBB)
      participate in stroke progression and recovery, we generated a mouse model of
      transient middle cerebral artery occlusion (tMCAO). After 1 h of occlusion
      followed by nearly complete reperfusion, the neurological deficits lasted more
      than a week as shown by several behavioral tests. Despite the prominent infarct
      area indicated by reduced cerebral perfusion and confirmed by vital staining, the
      volume of distribution of (131)I-albumin in various brain regions was not
      significantly altered over time (12 h to 14 days). In sharp contrast, the blood
      to-brain permeation of 125I-TNFalpha was significantly increased 5 days after
      tMCAO. Furthermore, excess unlabeled TNFalpha abolished this enhanced 125I
      TNFalpha uptake. Thus, not only did the known saturable transport system for
      TNFalpha persist, but it functioned at a higher capacity in tMCAO mice.
      Upregulation of TNFR1 and TNFR2 partially explains the increased transport, as
      mRNA for both receptors showed the most pronounced increase (15-fold and 30-fold,
      respectively) in the ischemic hemisphere 5-7 days after tMCAO. However, even in
      the hemisphere contralateral to the ischemia induced by stroke, there was
      increased TNFalpha transport. The bilateral increase in 125I-TNFalpha entry from
      blood to brain suggests that TNFalpha trafficking in cerebral endothelial cells
      is influenced by global mediators in addition to the transporting receptors.
      Given the known multiple modulatory effects of TNFalpha after stroke, the results
      indicate that the TNFalpha transport system at the BBB facilitates
      neuroplasticity and plays an important role in stroke recovery.

PMID- 16412422
TI  - The A-loop, a novel conserved aromatic acid subdomain upstream of the Walker A
      motif in ABC transporters, is critical for ATP binding.
AB  - ATP-binding cassette (ABC) transporters represent one of the largest families of
      proteins, and transport a variety of substrates ranging from ions to amphipathic
      anticancer drugs. The functional unit of an ABC transporter is comprised of two
      transmembrane domains and two cytoplasmic ABC ATPase domains. The energy of the
      binding and hydrolysis of ATP is used to transport the substrates across
      membranes. An ABC domain consists of conserved regions, the Walker A and B
      motifs, the signature (or C) region and the D, H and Q loops. We recently
      described the A-loop (Aromatic residue interacting with the Adenine ring of ATP),
      a highly conserved aromatic residue approximately 25 amino acids upstream of the
      Walker A motif that is essential for ATP-binding. Here, we review the mutational
      analysis of this subdomain in human P-glycoprotein as well as homology modeling,
      structural and data mining studies that provide evidence for a functional role of
      the A-loop in ATP-binding in most members of the superfamily of ABC transporters.

PMID- 16412423
TI  - Transcription factor cycling on the insulin promoter.
AB  - Using MIN6 beta-cells and chromatin immunoprecipitation (ChIP) assays, the
      chronological sequence of binding of MafA, E47/beta2 and PDX-1 to the insulin
      promoter in living beta-cells were investigated. All four factors were shown to
      bind to the mouse insulin 2 promoter in a cyclical manner with a periodicity of
      approximately 10-15 min. The cyclical binding of MafA, E47 and beta2 was largely
      unaffected by the glucose or insulin concentration in the media. However, the
      binding and cycling of PDX-1 was markedly abolished in low glucose (1 mM), and
      this was reversed in the presence of low concentrations of insulin.

PMID- 16412424
TI  - Cepharanthine triggers apoptosis in a human hepatocellular carcinoma cell line
      (HuH-7) through the activation of JNK1/2 and the downregulation of Akt.
AB  - Cepharanthine (CEP), a biscoclaurine alkaloid, has been reported to induce cell
      death, however, the molecular mechanism of this phenomenon remains unclear. We
      herein report that CEP induced apoptosis in HuH-7 cells through nuclear
      fragmentation, DNA ladder formation, cytochrome c release, caspase-3 activation
      and poly-(ADP-ribose)-polymerase cleavage. CEP triggered the generation of
      reactive oxygen intermediates, the activation of mitogen activated protein kinase
      (MAPK) p38, JNK1/2 and p44/42, and the downregulation of protein kinase B/Akt.
      Antioxidants and SP600125, an inhibitor of JNK1/2, but not inhibitors of p38 MAPK
      and MEK1/2, significantly prevented cell death, thus implying that reactive
      oxygen species and JNK1/2 play crucial roles in the CEP-induced apoptosis of HuH
      7 cells.

PMID- 16412425
TI  - Effect of asymmetric distribution of phospholipids in ghost membrane from rat
      blood on peroxidation induced by ferrous ion.
AB  - This study used rat erythrocyte ghost membrane to investigate the effect of
      aminophospholipid distribution in biological membranes on oxidative
      susceptibility. Aminophospholipids, lipid peroxidation, and carbonyl compounds
      were quantified; plasma membrane structure was examined using atomic force
      microscopy (AFM) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Inside
      out vesicles (IOVs) had significantly more aminophospholipids and greater lipid
      peroxidation than right-side-out vesicles (ROVs). Spectrin bands in IOVs
      disappeared obviously than in ROVs as shown in SDS-PAGE. In both systems vesicle
      protein size increased significantly with oxidation. Proteins aggregated much
      more in IOVs than ROVs at 48 h. These observations suggest that IOVs were more
      susceptible to ferrous ion-induced peroxidation than ROVs and that asymmetric
      phospholipid distribution affects biomembranes' oxidative susceptibility.

PMID- 16412426
TI  - Interactions of the Escherichia coli hydrogenase biosynthetic proteins: HybG
      complex formation.
AB  - Assembly of the active site of the [NiFe]-hydrogenase enzymes involves a multi
      step pathway and the coordinated activity of many accessory proteins. To analyze
      complex formation between these factors in Escherichia coli, they were
      genomically tagged and native multi-protein complexes were isolated. This method
      validated multiple interactions reported in separate studies from several
      organisms and defined a new complex containing the putative chaperone HybG and
      the large subunit of hydrogenase 1 or 2. The complex also includes HypE and HypD,
      which interact with each other before joining the larger complex.

PMID- 16412427
TI  - Fully oxidized scrambled isomers are essential and predominant folding
      intermediates of cardiotoxin-III.
AB  - Scrambled isomers (X-isomers) are fully oxidized, non-native isomers of disulfide
      proteins. They have been shown to represent important intermediates along the
      pathway of oxidative folding of numerous disulfide proteins. A simple method to
      assess whether X-isomers present as folding intermediate is to conduct oxidative
      folding of fully reduced protein in the alkaline buffer alone without any
      supplementing thiol catalyst or redox agent. Cardiotoxin-III (CTX-III) contains
      60 amino acids and four disulfide bonds. The mechanism of oxidative folding of
      CTX-III has been systematically characterized here by analysis of the acid
      trapped folding intermediates. Folding of CTX-III was shown to proceed
      sequentially through 1-disulfide, 2-disulfide, 3-disulfide and 4-disulfide
      (scrambled) isomers as folding intermediates to reach the native structure. When
      folding of CTX-III was performed in the buffer alone, more than 97% of the
      protein was trapped as 4-disulfide X-isomers, unable to convert to the native
      structure due to the absence of thiol catalyst. In the presence of thiol catalyst
      (GSH) or redox agents (GSH/GSSG), the recovery of native CTX-III was 80-85%.
      These results demonstrate that X-isomers play an essential and predominant role
      in the oxidative folding of CTX-III.

PMID- 16412428
TI  - In vivo assessment of the significance of phosphorylation of the Arabidopsis
      chloroplast protein import receptor, atToc33.
AB  - atToc33 is a transit peptide receptor of the chloroplast outer envelope membrane,
      and possesses GTPase activity. In vitro, its transit peptide- and GTP-binding
      properties are abrogated by its phosphorylation at serine 181, which was proposed
      to represent an important regulatory mechanism. We mutated S181 to alanine (to
      prevent phosphorylation), and to aspartate and glutamate (to mimic the effects of
      phosphoserine), and expressed all three proteins in ppi1 (atToc33 knockout)
      plants using the native promoter. The mutants complemented ppi1 with equal
      efficiency in respect of all criteria tested, including protein import efficiency
      and light stress tolerance. The data suggest that atToc33 phosphorylation may not
      play an important role in vivo.

PMID- 16412429
TI  - Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone
      with a double unsaturated side chain under methylotrophic growth conditions.
AB  - Acyl-homoserine lactones (acyl-HSLs) have emerged as important regulatory
      molecules for many gram-negative bacteria. We have found that Methylobacterium
      extorquens AM1, a member of the pink-pigmented facultative methylotrophs commonly
      present on plant surfaces, produces several acyl-HSLs depending upon the carbon
      source. A novel HSL was discovered with a double unsaturated carbon chain (N
      (tetradecenoyl)) (C14:2) and characterized by MS and proton NMR. This long-chain
      acyl-HSL is synthesized by MlaI that also directs synthesis of C14:1-HSL. The
      Alphaproteobacterium also produces N-hexanoyl-HSL (C6-HSL) and N-octanoyl-HSL (C8
      HSL) via MsaI.

PMID- 16412430
TI  - Efficient delivery of siRNA into cytokine-stimulated insulinoma cells silences
      Fas expression and inhibits Fas-mediated apoptosis.
AB  - Fas/FasL interactions have been proposed as a potentially important mechanism
      mediating beta-cell death in type 1 diabetes. Recent investigations suggest RNA
      interference, afforded by small interfering RNAs (siRNA), can provide specific
      and robust gene silencing in mammalian cells. The current study attempted to
      investigate the effects of silencing Fas expression with siRNA on Fas-mediated
      apoptosis in mouse insulinoma cells following cytokine incubation. Our results
      indicate that siRNA is capable of rapid inhibition of cytokine-induced Fas mRNA
      production and cell surface Fas protein. A complete suppression of the total Fas
      protein was only observed after prolonged incubation with siRNA, suggesting a
      slow turn-over of Fas protein. Moreover, siRNA significantly inhibited Fas
      mediated beta-cell apoptosis assessed by Caspase-3 and terminal deoxynucleotidyl
      transferase biotin-dUTP nick end labeling assays, the extent of which positively
      correlated with the level of cell surface Fas. These observations provide
      additional evidence supporting a role for the Fas-mediated pathway in beta-cell
      destruction, and suggest that siRNA targeting Fas may be of therapeutic value in
      preventing type 1 diabetes and improving islet cell viability in transplantation.

PMID- 16412431
TI  - Myelin basic protein, an autoantigen in multiple sclerosis, is selectively
      processed by human trypsin 4.
AB  - Demyelination, the proteolytic degradation of the major membrane protein in
      central nervous system, myelin, is involved in many neurodegenerative diseases.
      In the present in vitro study the proteolytic actions of calpain, human trypsin 1
      and human trypsin 4 were compared on lipid bound and free human myelin basic
      proteins as substrates. The fragments formed were identified by using N-terminal
      amino acid sequencing and mass spectrometry. The analysis of the degradation
      products showed that of these three proteases human trypsin 4 cleaved myelin
      basic protein most specifically. It selectively cleaves the Arg79-Thr80 and Arg97
      Thr98 peptide bonds in the lipid bound form of human myelin basic protein. Based
      on this information we synthesized peptide IVTPRTPPPSQ that corresponds to
      sequence region 93-103 of myelin basic protein and contains one of its two
      trypsin 4 cleavage sites, Arg97-Thr98. Studies on the hydrolysis of this
      synthetic peptide by trypsin 4 have confirmed that the Arg97-Thr98 peptide bond
      is highly susceptible to trypsin 4. What may lend biological interest to this
      finding is that the major autoantibodies found in patients with multiple
      sclerosis recognize sequence 85-96 of the protein. Our results suggest that human
      trypsin 4 may be one of the candidate proteases involved in the pathomechanism of
      multiple sclerosis.

PMID- 16412432
TI  - Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes
      leading to oxidative DNA breakage: a putative mechanism for anticancer
      properties.
AB  - Plant polyphenols are important components of human diet and a number of them are
      considered to possess chemopreventive and therapeutic properties against cancer.
      They are recognized as naturally occurring antioxidants but also act as
      prooxidants catalyzing DNA degradation in the presence of transition metal ions
      such as copper. Using human peripheral lymphocytes and Comet assay we have
      previously confirmed that resveratrol-Cu(II) is indeed capable of causing DNA
      degradation in cells. In this paper we show that the polyphenols alone (in the
      absence of added copper) are also capable of causing DNA breakage in cells.
      Incubation of lymphocytes with neocuproine inhibited the DNA degradation
      confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further,
      we have also shown that polyphenols generate oxidative stress in lymphocytes
      which is inhibited by scavengers of reactive oxygen species and neocuproine.
      These results are in further support of our hypothesis that anticancer mechanism
      of plant polyphenols involves mobilization of endogenous copper, possibly
      chromatin bound copper, and the consequent prooxidant action.

PMID- 16412434
TI  - The AP-1/CJUN signaling cascade is involved in muscle differentiation:
      implications in muscle wasting during cancer cachexia.
AB  - The aim of the present study was to investigate a possible role of the AP-1
      signaling cascade in the process of wasting associated with cancer cachexia at
      the level of skeletal muscle. The injection of virus containing the TAM67 protein
      (a blocker of the AP-1 protein) to the gastrocnemius muscle of tumour-bearing
      rats resulted in a significant recovery of the muscle mass (which is dramatically
      reduced as a result of tumour burden), therefore suggesting that AP-1 is
      certainly involved in the signaling associated with muscle protein accretion. In
      conclusion, the gene therapy approach presented here clearly suggests an
      important role for AP-1 in muscle signaling during catabolic states.

PMID- 16412435
TI  - Molecular dynamics study of major urinary protein-pheromone interactions: a
      structural model for ligand-induced flexibility increase.
AB  - Recently, two independent (15)N NMR relaxation studies indicated that in contrast
      to the decreased flexibility expected for induced-fit interactions, the backbone
      flexibility of major urinary protein isoform I (MUP-I) slightly increased upon
      complex formation with its natural pheromone 2-sec-butyl-4,5-dihydrothiazol. We
      have investigated the subtle details of molecular interactions by molecular
      dynamics simulations in explicit solvent. The calculated order parameters S(2)
      for a free- and ligand-bound protein supply evidence that mobility in various
      regions of MUP-I can be directly related to small conformational changes of the
      free- and complexed protein resulting from modifications of the hydrogen bonding
      network.

PMID- 16412436
TI  - Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as
      a transcriptional repressor.
AB  - Previously, we reported that decreased brain-specific angiogenesis inhibitor 2
      (BAI2) induced increased VEGF expression. The regulatory mechanisms for this
      process are not understood. Here we show that GA-binding protein gamma
      (GABPgamma) associates with the cytoplasmic domain of BAI2, and GABPalpha/gamma
      or GABPalpha/beta works as a transcriptional repressor of VEGF in SHSY5Y cells.
      Transcriptional activity of wild-type VEGF promoter was significantly increased
      in anti-sense BAI2-transfected cells, but not that of VEGF promoter harboring
      mutated GABP sites. In in vivo focal cerebral ischemia model, the decrease in
      BAI2 accompanied by decreased GABPalpha and GABPgamma elicited increased VEGF
      expression before the onset of HIF-1alpha. Our results point out that BAI2
      controls VEGF transcription through GABP under normal conditions and cerebral
      ischemia.

PMID- 16412437
TI  - DNA polymerization by the reverse transcriptase of the human L1 retrotransposon
      on its own template in vitro.
AB  - L1 elements (LINE-1s) account for 17% of the human genome and have achieved this
      abundance by transpositions via an RNA intermediate, or retrotransposition.
      Reverse transcription is a crucial event in the retrotransposition of the active
      human L1 element and is carried out by the L1-encoded ORF2 protein. Previously,
      we performed biochemical characterization of the human L1 ORF2 protein with
      reverse transcriptase (RT) activity (referred to as L1 RT), expressed in
      baculovirus-infected insect cells. In the present study, we describe the
      properties of DNA- and RNA-dependent DNA synthesis catalyzed by the L1 RT on the
      L1 templates in vitro. We found that L1 RT synthesized at least 620 of
      nucleotides per template binding event utilizing L1 RNA in vitro. Under
      processive conditions the L1 RT synthesized cDNA over 5 times longer than that
      Moloney murine leukemia virus RT on the heteropolymeric RNA template used in
      these studies. These data are the first to demonstrate that RT from the human L1
      element is a highly processive polymerase among RT enzymes. This report also
      presents a strong evidence of lack of RNase H activity for the L1 ORF2 protein in
      vitro, distinguishing L1 RT from retroviral RTs. Finally, we found strong pausing
      for of the L1 RT during DNA polymerization within the 3' untranslated region of
      L1 mRNA, that is result of contribution both rGs runs of the polypurine stretch
      and immediately adjacent stem-loop structure. A mechanism facilitating minus
      strand DNA synthesis during reverse transcription of L1 element in vivo is
      discussed.

PMID- 16412438
TI  - Role of the p53 homologue from Drosophila melanogaster in the maintenance of
      histone H3 acetylation and response to UV-light irradiation.
AB  - It has been demonstrated that the human tumor suppressor p53 has an important
      role in modulating histone modifications after UV light irradiation. In this work
      we explored if the p53 Drosophila homologue has a similar role. Taking advantage
      of the existence of polytene chromosomes in the salivary glands of third instar
      larvae, we analyzed K9 and K14 H3 acetylation patterns in situ after UV
      irradiation of wild-type and Dmp53 null flies. As in human cells, after UV damage
      there is an increase in H3 acetylation in wild-type organisms. In Dmp53 mutant
      flies, this response is significantly affected at the K9 position. These results
      are similar to those found in human p53 mutant tumor cells with one interesting
      difference, only the basal H3 acetylation of K14 is reduced in Dmp53 mutant
      flies, while the basal H3-K9 acetylation is not affected. This work shows, that
      the presence of Dmp53 is necessary to maintain normal H3-K14 acetylation levels
      in Drosophila chromatin and that the function of p53 to maintaining histone
      modifications, is conserved in Drosophila and humans.

PMID- 16412440
TI  - Differential expression of IGF-I mRNA and peptide in the male and female gonad
      during early development of a bony fish, the tilapia Oreochromis niloticus.
AB  - Insulin-like growth factor I (IGF-I) plays a key role in the complex system that
      regulates bony fish growth, differentiation, and reproduction. The major source
      of circulating IGF-I is liver, but IGF-I-producing cells also occur in other
      organs, including the gonads. Because no data are available on the potential
      production sites of IGF-I in gonad development, developmental stages of monosex
      breedings of male and female tilapia from 0 day postfertilization (DPF) to 90 DPF
      were investigated for the production sites of IGF-I at the peptide
      (immunohistochemistry) and mRNA (in situ hybridization) level. IGF-I mRNA first
      appeared in somatic cells of the male and female gonad anlage at 7 DPF followed
      by IGF-I peptide around 9-10 DPF. Gonad anlagen were detected from 7 DPF.
      Starting at 7 DPF, IGF-I peptide but no IGF-I mRNA was observed in male and
      female primordial germ cells (PGCs) provided that IGF-I mRNA was not under the
      detection level, this observation may suggest that IGF-I originates from the
      somatic cells and is transferred to the PGCs or is of maternal origin. While in
      female germ cells IGF-I mRNA and peptide appeared at 29 DPF, in male germ cells
      both were detected as late as at 51-53 DPF. It is assumed that the production of
      IGF-I in the germ cells is linked to the onset of meiosis that in tilapia ovary
      starts at around 28 DPF and in testes at around 52-53 DPF. In adult testis, IGF-I
      mRNA and peptide occurred in the majority of spermatogonia and spermatocytes as
      well as in Leydig cells, the latter indicating a role of IGF-I in the synthesis
      of male sex steroids. In adult ovary, IGF-I mRNA and IGF-I peptide were always
      present in small and previtellogenic oocytes but only IGF-I peptide infrequently
      occurred in oocytes at the later stages. IGF-I expression appeared in numerous
      granulosa and some theca cells of follicles at the lipid stage and persisted in
      follicles with mature oocytes. The results suggest a crucial role of local IGF-I
      in the formation, differentiation and function of tilapia gonads.

PMID- 16412439
TI  - Stoichiometry of lipid-protein interaction assessed by hydrophobic photolabeling.
AB  - Here we undertook a comparative study of the composition of the lipid annulus of
      three ATPases pertaining to the P-type family: plasma membrane calcium pump
      (PMCA), sarcoplasmic reticulum calcium pump (SERCA) and Na,K-ATPase. The
      photoactivatable phosphatidylcholine analogue [(125)I]TID-PC/16 was incorporated
      into mixtures of dimyristoyl phosphatidylcholine (DMPC) and each enzyme with the
      aid of the nonionic detergent C(12)E(10). After photolysis, the extent of the
      labeling reaction was assessed to determine the lipid:protein stoichiometry: 17
      for PMCA, 18 for SERCA, 24 for the Na,K-ATPase (alpha-subunit) and 5.6 mol PC/mol
      protein for the Na,K-ATPase (beta-subunit).

PMID- 16412441
TI  - Os acromiale: population differences and their etiological significance.
AB  - The os acromiale is an accessory bone resulting from failure of the acromial
      apophysis to fuse to the scapula. It is a relatively frequent defect affecting 4
      18% of most large skeletal series. The etiology of os acromiale is poorly
      understood, and two competing hypotheses have been proposed: (1) that the
      accessory bone represents a genetic defect, and (2) that it results from
      mechanical stress on the developing acromion. In order to assess the evidence for
      these two hypotheses, os acromiale frequencies from a South African cadaver
      sample (n = 494) were compared to frequencies from a medieval Danish
      archaeological sample (n = 532). The South African frequency (18.2%) was
      significantly higher than the medieval Danish frequency (7.7%, p < 0.0001). These
      results mirror those of another study comparing African- and Euro-Americans, and
      tend to support the genetic hypothesis. However, a left side bias (72%) was also
      found among the South Africans (p = 0.013), lending some support to the
      mechanical stress hypothesis. Sex and age biases were also examined but were not
      found. In order to further test the mechanical hypothesis, the medieval Danes
      were divided into groups of higher and lower socioeconomic status based upon
      cemetery type. Lower status individuals were presumed to have engaged in
      strenuous labor activities more often and at a younger age than higher status
      individuals. However, comparison of these two groups failed to demonstrate a
      significant frequency difference (p = 0.105). Based on the results of this study,
      it is suggested that a third etiology combining a genetic predisposition for os
      acromiale with mechanical stress as the proximate cause should also be
      considered.

PMID- 16412442
TI  - From Husserl to van Manen. A review of different phenomenological approaches.
AB  - This paper traces the development of phenomenology as a philosophy originating
      from the writings of Husserl to its use in phenomenological research and theory
      development in nursing. The key issues of phenomenological reduction and
      bracketing are also discussed as they play a pivotal role in the how
      phenomenological research studies are approached. What has become to be known as
      "new" phenomenology is also explored and the key differences between it and
      "traditional" phenomenology are discussed. van Manen's phenomenology is also
      considered in light of its contemporary popularity among nurse researchers.

PMID- 16412443
TI  - Evaluation of a MS specialist nurse programme.
AB  - BACKGROUND: Specialist nurses are being promoted as a means of improving the
      health care provided to people with multiple sclerosis (MS). OBJECTIVES: To
      identify the impact of a programme of MS specialist nurses on MS health care
      provision and on the health and well-being of people with MS. DESIGN: A quasi
      experimental design comparing an intervention group in which new MS nurse posts
      were installed with a control group that had no MS nurse posts. SETTING: Six
      neurological services in four English regions. PARTICIPANTS: Seven hundred and
      fifty-three of the 1510 people invited to participate returned completed
      questionnaires at baseline. Follow-up of participants was 82% with 616 patients
      participating in the main outcome analysis. METHOD: Data were collected
      prospectively before the appointment of the MS nurses and then at 12 and 24
      months. Data were collected via a postal questionnaire comprising questions
      related to care processes (information provision and care quality) and health
      outcome measures, hospital admissions, MS complications, health-related quality
      of life (SF36) and disease impact (MS Impact Scale-29). Analysis repeated
      measures in CAT MOD for process variables and ANCOVA to longest follow-up for
      outcome measures. RESULTS: Information provision was higher in the intervention
      group (68% (n=153) compared to 53% (n=98) at 24 months) but no significant
      improvement was observed in information provision through time compared to the
      control group. There was an increase in the availability of a contact person in
      the intervention group, at 24 months 83% (n=42) had a contact person compared to
      44% in the control (p=0.01). The only significant finding in relation to MS
      complications was a reduction of 17% in the incidence of pressure ulcers in the
      intervention sites compared to a 3% reduction in the control (p<0.001). In
      relation to the disease and health-related quality of life measures, the
      intervention group showed a small but significant (p<0.05) worsening in the
      physical and symptom scales of the SF36 compared to the control (mean
      differences: physical function -2.81, CI -5.45 to -0.1; bodily pain -4.09, CI 
      7.2 to -0.9; general health -5.35, CI -8.1 to -2.5; and energy and vitality 
      2.82, CI -5.5 to -0.1). No differences were observed in relation to disease
      impact or psychosocial well-being, although a relative benefit in mental health
      (with a 7.8 point advantage on the SF36 mental health scale, p=0.04) was observed
      in some of the intervention sites for people with relapsing/remitting MS.
      CONCLUSION: The specialist nurse programme was found to impact positively on the
      provision of MS-related health care. However, there was very limited evidence
      that the programme led to any improvements in disease-related problems, impact or
      health-related quality of life, These findings were in part explained by the
      inherent difficulties of measuring effects in evaluations of complex phenomena
      such as a nursing role. The deterioration observed in the intervention group on
      the physical outcome measures was explained by a selection bias in which people
      with worsening health were more likely to seek contact with a specialist nurse.
      It is contended that future research in this area may be better directed toward
      identifying specific interventions that nurses and other health professionals
      might employ in addressing the many problems confronting people with MS.

PMID- 16412444
TI  - Learning partnership--the experience of peer tutoring among nursing students: a
      qualitative study.
AB  - BACKGROUND: Peer tutoring involves students helping each other to learn. It
      places teaching and learning commitments and responsibilities on students.
      Considerable evidence supports the positive effects of peer tutoring, including
      cognitive gains, improved communication, self-confidence, and social support
      among students. Peer tutors are also said to better understand the learning
      problems of fellow peer learners than teachers do. OBJECTIVE: This study intended
      to facilitate the development of 'cooperative learning' among nursing students
      through a peer-tutoring scheme. STUDY METHOD: Undergraduate nursing students were
      invited to join a peer-tutoring scheme. Fourteen students studying year 3 were
      recruited to serve as peer tutors and 16 students from year 2 of the same program
      participated as tutees. Peer tutors attended a training workshop and received a
      guideline for peer-tutoring activities. They were to provide a total of '10
      weekly tutoring sessions throughout the semester on a one-to-one basis for their
      tutees. Focus groups and individual interviews were conducted in the middle and
      at the end of the semester to evaluate the students' experiences in the tutoring
      process. RESULTS: Content analysis of the interview scripts identified that
      students had both positive and negative experiences from the peer tutoring, but
      that positive experiences predominated. Positive aspects included enhancement of
      learning skills/intellectual gains and personal growth. Negative experiences
      stemmed mainly from frustrations in dealing with mismatched learning styles
      between tutors and tutees, and the required time commitment. CONCLUSIONS: Both
      tutors and tutees benefited to some extent from this peer-tutoring process.
      Further studies in an education program for students in all years should be
      implemented to examine peer-tutoring effects. Implementation of peer tutoring
      should address the frustrations and difficulties encountered by the students to
      facilitate better outcomes.

PMID- 16412445
TI  - In whose best interests? Nurses' experiences of the administration of sedation in
      general medical wards in England: an application of the critical incident
      technique.
AB  - BACKGROUND: Despite concern expressed in recent government documents in the UK
      about the inappropriate use of sedation when a patient is agitated or confused
      and cannot consent, there is little nursing literature on the topic. The general
      legal and ethical principles apply that a patient who is unable to consent should
      be given care that is in his or her 'best interests'. AIM: The aim of this paper
      is to report on qualitative data concerning nurses' use of sedation which were
      obtained as part of a larger study to explore the way in which nurses obtain
      consent prior to nursing care procedures. METHOD: A purposive sample of 30
      qualified nurses in two teaching hospitals in England was obtained. One hundred
      critical incidents were collected through 30 in-depth interviews as a means of
      focusing on specific incidents concerning informed consent prior to nursing care
      procedures in clinical practice. FINDINGS: The administration of sedation to
      patients who cannot consent was a major theme to emerge. Sedation was sometimes
      given in the interests of other patients or staff rather than the patient and
      before alternative strategies had been considered. Nurses were uneasy about the
      use of sedation in such circumstances, and lacked knowledge as to when it may be
      appropriate to do so. CONCLUSIONS: Nurses need to be familiar with the relevant
      ethical and legal principles and professional guidance in their own countries for
      caring for people who cannot consent, and need to be confident in their
      understanding and application of these principles to ensure that sedation is
      administered appropriately.

PMID- 16412446
TI  - Does oxidative stress change ceruloplasmin from a protective to a vasculopathic
      factor?
AB  - Although ceruloplasmin (CP), a copper containing metalloenzyme, possesses
      antioxidant properties (e.g. ferroxidase activity), elevated circulating CP is
      associated with cardiovascular disease (CVD). This ambivalence is possibly due to
      the capacity of CP, via its coppers, to promote vasculopathic effects that
      include lipid oxidation, negation of nitric oxide bioactivity and endothelial
      cell apoptosis. In turn, these effects that are mediated by increased formation
      of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. There
      is also evidence that risk factors for CVD (in particular, diabetes mellitus and
      hyperhomocysteinaemia) may augment the vasculopathic impact of CP. In turn, it
      appears that ROS disrupt copper binding to CP, thereby impairing its normal
      protective function while liberating copper which in turn may promote oxidative
      pathology. The objective of this review, therefore, is to consider the
      epidemiology and pathophysiology of CP in relation to CVD, with particular
      emphasis on the relationship between CP and oxidative stress.

PMID- 16412447
TI  - Proceedings of the 28th International Symposium on Capillary Chromatography and
      Electrophoresis, Las Vegas, Nevada, USA, 22-25 May 2005.

PMID- 16412448
TI  - Evaluation of contactless conductivity detection for the determination of UV
      absorbing and non-UV absorbing species in reversed-phase high-performance liquid
      chromatography.
AB  - A capacitively coupled contactless conductivity detector (C(4)D) was used for the
      determination of three groups of ionizable species in reversed-phase HPLC with
      isocratic elution. These were non-steroidal anti-inflammatory drugs which are
      arylpropionic acid derivatives and represent anionic analytes, beta-blockers
      which are amines and therefore cationic, and zwitterionic amino acids.
      Optimization of the eluents led to detection limits in the order of 1 microM for
      all species. The precision in peak areas was typically between 0.2 and 2.1% and
      calibration curves were linear up to 500 microM. The determination of ibuprofen,
      acetylsalicylic acid and atenolol in real samples was also demonstrated by direct
      injection of dissolved pharmaceutical formulations into the HPLC-C(4)D system.

PMID- 16412449
TI  - Determination of alkylphenols and alkylphenol carboxylates in wastewater and
      river samples by hemimicelle-based extraction and liquid chromatography-ion trap
      mass spectrometry.
AB  - Sodium dodecyl sulfate (SDS)-coated alumina and cetylpyridinium chloride (CPC)
      coated silica were investigated as new sorbents for the concentration of
      alkylphenol polyethoxylate (APE) biodegradation products from wastewater and
      river water samples. Octylphenol (OP), nonylphenol (NP), octylphenol carboxylic
      acid (OPC) and nonylphenol carboxylic acid (NPC) were quantitatively retained on
      both supramolecular sorbents on the basis of the formation of mixed hemimicelles
      and admicelles. SDS hemimicelles-based SPE was proposed for the
      extraction/concentration of the target compounds prior to their separation and
      quantitation by liquid chromatography/electrospray ionization in negative mode,
      ion trap mass spectrometry. No clean-up steps or evaporation of the eluent were
      required. The recovery of APE metabolites from sewage and river water ranged
      between 87 and 100%. Concentration factors of about 500, using sample volumes of
      1 l, were achieved. Detection limits were between 75 and 193 ng/l. The approach
      developed was applied to the determination of alklylphenols and alkylphenol
      carboxylic acids in raw and treated sewage and river samples. The concentrations
      of APE metabolites found ranged between 0.8 and 78 microg/l.

PMID- 16412450
TI  - Application of cellulose and amylose arylcarbamates as chiral selectors in
      counter-current chromatography.
AB  - Here we studied the applicability of cellulose and amylose tris(3,5
      dimethylphenylcarbamate) as chiral selectors for the separation of enantiomers by
      counter-current chromatography (CCC). A variety of organic/aqueous biphasic
      solvent systems and eight racemic analytes of acidic, neutral, and basic nature
      were tested for this purpose. Classical elution mode and pH-zone-refining
      displacement conditions were used. Partial enantioseparation of pindolol and
      warfarin was achieved in methyl isobutyl ketone (MIBK)/aqueous solution and
      methyl tert-butyl ether (MTBE)/aqueous solution, respectively. For these two
      racemates enantiomeric excess values from 84% to 97% were achieved under the best
      conditions tested. However, resolution by CCC was not achieved for propranolol,
      naproxen and N-(3,5-dinitrobenzoyl)-(+/-)-leucine, easily separated in HPLC by
      the same selectors.

PMID- 16412451
TI  - A practical approach to maximizing peak capacity by using long columns packed
      with pellicular stationary phases for proteomic research.
AB  - Maximization of peak capacity is a very important step in developing one
      dimensional separations of complex samples. In recent work, it was shown that the
      use of small particles in combination with the new technique of ultrahigh
      pressure liquid chromatography (UHPLC) was able to generate very high peak
      capacities. Here we show the ability of conventional HPLC instrumentation to give
      comparable peak capacities to those obtained in UHPLC for the important case of
      complex mixtures of peptides but at much lower pressures by using a 60 cm long
      set of columns packed with 5 microm pellicular (superficially porous) particles.
      We first show, in complete agreement with the well known results of the theory of
      isocratic separations that, when time is not limiting, the best peak capacities
      in gradient elution chromatography are obtained by using large particles and the
      longest column that can be operated at the pump's pressure limit. Two different
      types of 5 microm particles (superficially porous and totally porous) were
      compared for their efficiency in gradient chromatography of peptides. We find
      that the pellicular material gave about 50% higher peak capacity compared to the
      analogous porous material. A 60 cm column set packed with pellicular particles
      was made by connecting short columns in series; a peak capacity of about 460 was
      obtained in 4 h at room temperature. Increasing the column temperature to 70
      degrees C reduced the analysis time to 2 h and further increased the peak
      capacity to more than 500. The number of peaks observed in the separation of
      bovine serum albumin tryptic peptides was greatly increased and the separation
      quality was significantly improved.

PMID- 16412452
TI  - Development of a hydrophilic interaction chromatography-mass spectrometry assay
      for spectinomycin and lincomycin in liquid hog manure supernatant and run-off
      from cropland.
AB  - A specific and sensitive analytical method was developed to extract and quantify
      spectinomycin and lincomycin in liquid hog manure supernatant and simulated
      rainfall run-off from manure-treated cropland. Sample extracts were prepared
      using solid-phase extraction (SPE) employing a weak cation-exchange resin (Oasis
      WCX) for extraction of spectinomycin. An Oasis HLB cartridge was used for
      extraction of lincomycin. Hydrophilic interaction chromatography (HILIC) was used
      to obtain the necessary separation of the two antibiotics from interfering
      compounds and to provide baseline separation. Analytes were detected using
      atmospheric pressure chemical ionization tandem mass spectrometry. Extraction
      recoveries were 77% for lincomycin and 84% for spectinomycin in liquid hog manure
      supernatant, and 89% for lincomycin and 95% for spectinomycin in run-off water.
      The corresponding limits of quantitation were 6.0 and 0.040 microg l(-1) for
      spectinomycin and lincomycin, respectively, in liquid hog manure supernatant and
      0.2 and 0.008 microg l(-1) for spectinomycin and lincomycin, respectively, in run
      off from manure treated cropland. The method is suitable for monitoring the
      environmental fate and transport of these two antibiotics in both liquid hog
      manure and agricultural field run-off.

PMID- 16412453
TI  - Effect of temperature on the retention of amino acids and carbohydrates in high
      performance anion-exchange chromatography.
AB  - Effect of temperature on the retention of amino acids and carbohydrates in high
      performance anion-exchange chromatography (HPAEC) was investigated. Amino acids
      retention exhibited both exothermic and endothermic behavior. Significant
      selectivity variations of some weakly retained amino acids were achieved through
      changing temperature. However, temperature was almost ineffective at changing the
      selectivity of strongly retained amino acids. Sugars retention exhibited only
      exothermic behavior. However, individual carbohydrates showed different relative
      changes in retention time with increased temperature. There is the general
      regularity, which is the variation of retention time increases as the sequence of
      monosaccharide, disaccharide, trisaccharide and tetrasaccharide when the column
      temperature is increased. Selectivity changes of carbohydrates, including elution
      order reversal, were also achieved by varying temperature. Temperature was
      effective at changing the selectivity of between amino acids and carbohydrates.
      In achieving optimal separation of amino acids and carbohydrates, temperature is
      a valuable tool.

PMID- 16412454
TI  - pH-responsive, self-assembling nanoparticle from a fullerene-tagged poly(L
      glutamic acid) and its superoxide dismutase mimetic property.
AB  - In this study, we describe the fabrication of novel fullerene-containing peptide
      nanoparticles through self-assembly. A water-soluble, poly(l-glutamic acid)
      attached fullerene was newly synthesized and the conformation and self-assembling
      property in water were examined by using circular dichroism, FTIR, UV, atomic
      force microscopy, and dynamic light scattering measurements. In the lower pH
      region (<6.8), the fullerene peptide self-assembles into nanoparticles that are
      ca. 100-200 nm in diameter. These nanoparticles are rich in alpha-helices, and
      stacking interaction of fullerene moieties contributes to the stability of the
      high-order structure. In addition, these particle sizes can be easily controlled
      by changing pH that results in causing the conformational transition of PLGA
      segment. Finally, the fullerene-containing nanoparticle is confirmed to be
      capable of removing the biologically important superoxide radical in comparison
      with the superoxide dismutase.

PMID- 16412455
TI  - Numerical investigation of the effect of insoluble surfactants on drop
      deformation and breakup in simple shear flow.
AB  - The effect of insoluble surfactants on drop deformation and breakup in simple
      shear flow is studied using a combination of a three-dimensional boundary
      integral method and a finite-volume method to solve the coupled fluid dynamics
      and surfactant transport problem over the evolving interface. The interfacial
      tension depends nonlinearly on the surfactant concentration, and is described by
      the equation of state for the Langmuir isotherm. Results are presented over the
      entire range of the viscosity's ratio lambda and the surface coverage x, as well
      as the capillary number Ca that spans from that for small deformation to values
      that are beyond the critical one Ca(cr). The values of the elasticity number E,
      which reflects the sensitivity of the interfacial tension to the maximum
      surfactant concentration, are chosen in the interval 0.1 < or = E < or = 0.4 and
      a convection dominated regime of surfactant transport, where the influence of the
      surfactant on drop deformation is the most significant, is considered. For a
      better understanding of the processes involved, the effect of surfactants on the
      drop dynamics is decoupled into three surfactant related mechanisms (dilution,
      Marangoni stress and stretching) and their influence is separately investigated.
      The dependence of the critical capillary number Ca(cr)(lambda) on the surface
      coverage is obtained and the boundaries between different modes of breakup (tip
      streaming and drop fragmentation) in the (lambda; x) plane are searched for. The
      numerical results indicate that at low capillary number, even with a trace amount
      of surfactant, the interface is immobilized, which has also been observed by
      previous studies. In addition, it is shown that for large Peclet numbers the use
      of the small deformation theory to measure the interfacial tension in the case
      where surfactants are present can introduce a significant error.

PMID- 16412456
TI  - Response to genistein: assaying the activation status and chemotaxis efficacy of
      isolated neutrophils.
AB  - Neutrophil (PMN) activation and chemotaxis toward inflammatory stimuli play
      critical roles in host defense and tissue inflammation. To determine the
      molecular mechanisms that regulate PMN function, many studies currently employ in
      vitro PMN activation and transmigration assays using freshly isolated peripheral
      PMN or PMN isolated from bone marrow. However, due to the highly sensitive nature
      of PMN, cell activation or priming can occur during isolation, which demands
      assay(s) that ensure the consistency of isolated PMN prior to using them in
      subsequent experiments. Here, we introduce a simple screening assay based on the
      observation that in transmigration assays, isolated PMN differentially respond to
      the tyrosine kinase inhibitor genistein and this is related to their activation
      status. As shown, we observed that isolated PMN for which early migration is
      enhanced by genistein have an overall high transmigration efficacy and that over
      80% of applied PMN migrate across collagen-coated filters in a 2 h time period.
      Conversely, the inhibitory/non-enhancement effect of genistein is accompanied by
      a poor PMN transmigration, with less than 25% of applied PMN transmigrating
      across. Further analysis of PMN spontaneous adhesion, degranulation and cell
      surface CD11b/CD18 expression suggests that reduced migration of PMN is
      associated with PMN activation/priming that happens, in most cases, during the in
      vitro cell isolation procedure regardless of the blood donor. Thus, based on
      these observations, we developed a "genistein assay" to directly predict PMN
      status after each isolation. From our experience, this assay has not only
      revealed new insights into the mechanisms of PMN activation and assisted in
      functional assays, but it has also provided a method that can be mastered by both
      inexperienced and experienced researchers to assay isolated PMN and thus avoid
      using inconsistent cells (e.g. pre-activated PMN) in their experiments.

PMID- 16412457
TI  - Development of murine monoclonal antibodies to methamphetamine and
      methamphetamine analogues.
AB  - Methamphetamine and ecstasy are addictive drugs that cause major health problems
      in young people. Here we report on the development of high-affinity monoclonal
      antibodies to methamphetamine and its analogues, which may constitute powerful
      tools for antibody-based therapy. Six haptens, methamphetamine and ecstasy
      analogues, were synthesized, linked to a carrier protein and injected into mice.
      Several specific monoclonal antibodies were subsequently obtained following
      fusion of splenocytes from the immunized animals, with Sp2/O cells. Antibody
      specificity was fully investigated by competition ELISA, using a series of
      analogues, to identify specific amphetamine and/or ecstasy-specific antibodies.
      Antibody affinity was estimated to be in the range of 10(8) M(-1) with an
      enantiomeric hapten. Finally, two characteristic hybridoma clones (DAS-M243-6H5
      and DAS-M278-4B12), secreting specific and potent mAbs were isolated. The
      development of drug-specific antibodies as in this study may provide promising
      therapeutic insight into how to neutralize methamphetamine in vivo during acute
      intoxication.

PMID- 16412458
TI  - Metabolic changes associated with active water vapour absorption in the mealworm
      Tenebrio molitor L. (Coleoptera, Tenebrionidae): a microcalorimetric study.
AB  - Water vapour absorption (WVA) is an important mechanism for water gain in several
      xeric insects. Theoretical calculations indicate that the energetic cost of WVA
      should be small (5-10% of standard metabolic rate) assuming realistic
      efficiencies. In this study we explored the relationship between WVA, metabolic
      heat flux (HFmet.) and CO2 release in larvae of Tenebrio molitor using
      microcalorimetry. By comparing metabolic heat flux with the catabolic rate
      estimated from VCO2 , we were able to differentiate anabolic and catabolic rates
      prior to and during WVA, while simultaneously monitoring water exchange. Three to
      four hours before the onset of WVA, larvae showed clear increases in HFmet. and
      catabolic flux, and a simultaneous decrease in anabolic flux. Following the onset
      of WVA, HFmet. decreased again until indistinguishable from control (non
      absorbing) values. Possible factors contributing to the "preparatory phase" are
      discussed, including mobilization of Malpighian tubule transporters and muscular
      activity in the rectum. Absorbing larvae reduced the water activity of the
      calorimetric cell to 0.906, agreeing with gravimetric estimates of the critical
      equilibrium activity. Periods of movement during WVA coincided with decreased
      uptake fluxes, consistent with the animal's hydrostatic skeleton and the need to
      close the anus to generate pressure increases in the haemocoel.

PMID- 16412459
TI  - Regional variation in mRNA transcript abundance within the ventricular wall.
AB  - Previous studies have shown that regional variation in ion channel gene
      expression contributes to electrical heterogeneity within the walls of the
      cardiac ventricles. To map the extent of regional variation in gene expression in
      the ventricular walls and to begin to understand its genesis we have performed a
      microarray analysis of gene expression in the epicardial and endocardial tissues
      of the rat adult left ventricle. While the vast majority of the genes are
      expressed at uniform levels across the ventricular wall, a total of 36
      transcripts (representing less than 0.1% of the genes expressed in the ventricle)
      are expressed more abundantly in either epicardium or endocardium. One of these
      differentially expressed genes is the sodium channel gene Scn5a, which is
      expressed at higher levels in the endocardium than in the epicardium of rat
      heart. The transcription factor genes Irx3, Irx5 and Etv1 were found to be
      expressed in transmural gradients across the ventricular wall of rat heart and
      also of canine heart. The Irx3 and Irx5 genes were expressed in an inverse
      pattern to that of the Kcnd2 (Kv4.2) gene in rat heart, suggesting that these
      transcription factors may act as negative regulators of Kcnd2 expression in vivo.

PMID- 16412460
TI  - Neuronal BC1 RNA: microtubule-dependent dendritic delivery.
AB  - RNA localization is an important means of post-transcriptional regulation of gene
      expression in many eukaryotic cell types. In neurons, select RNAs are delivered
      to postsynaptic dendritic microdomains, a mechanism that is considered a key
      underpinning in the administration of long-term synaptic plasticity. BC1 RNA is a
      small untranslated RNA that interacts with translation initiation factors and
      functions as a translational repressor by targeting assembly of 48S initiation
      complexes. BC1 RNA is specifically and rapidly transported to dendrites where it
      is found concentrated in postsynaptic microdomains. The cytoskeletal
      infrastructure underlying dendritic localization of BC1 RNA has not been
      investigated. We now report that the dendritic delivery of BC1 RNA is dependent
      on intact microtubules. In two neuronal cell types, hippocampal neurons and
      sympathetic neurons in primary culture, disruption of microtubules abolished
      dendritic localization of BC1 RNA. In contrast, disruption of actin filaments had
      no significant effect on the somatodendritic distribution of BC1 RNA. It is
      concluded that the long-range dendritic delivery of BC1 RNA is supported by
      microtubules. At the same time, a role for actin filaments, while unlikely for
      long-range BC1 delivery, is not ruled out for short-range local translocation and
      anchoring at dendritic destination sites.

PMID- 16412461
TI  - Identification and analysis of deleterious human SNPs.
AB  - We have developed two methods of identifying which non-synonomous single base
      changes have a deleterious effect on protein function in vivo. One method,
      described elsewhere, analyzes the effect of the resulting amino acid change on
      protein stability, utilizing structural information. The other method, introduced
      here, makes use of the conservation and type of residues observed at a base
      change position within a protein family. A machine learning technique, the
      support vector machine, is trained on single amino acid changes that cause
      monogenic disease, with a control set of amino acid changes fixed between
      species. Both methods are used to identify deleterious single nucleotide
      polymorphisms (SNPs) in the human population. After carefully controlling for
      errors, we find that approximately one quarter of known non-synonymous SNPs are
      deleterious by these criteria, providing a set of possible contributors to human
      complex disease traits.

PMID- 16412462
TI  - Protein trans-splicing and characterization of a split family B-type DNA
      polymerase from the hyperthermophilic archaeal parasite Nanoarchaeum equitans.
AB  - Nanoarchaeum equitans family B-type DNA polymerase (Neq DNA polymerase) is
      encoded by two separate genes, the large gene coding for the N-terminal part (Neq
      L) of Neq DNA polymerase and the small gene coding for the C-terminal part (Neq
      S), including a split mini-intein sequence. The two Neq DNA polymerase genes were
      cloned and expressed in Escherichia coli individually, together (for the Neq C),
      and as a genetically protein splicing-processed form (Neq P). The protein trans
      spliced Neq C was obtained using the heating step at 80 degrees C after the co
      expression of the two genes. The protein trans-splicing of the N-terminal and C
      terminal parts of Neq DNA polymerase was examined in vitro using the purified Neq
      L and Neq S. The trans-splicing was influenced mainly by temperature, and
      occurred only at temperatures above 50 degrees C. The trans-splicing reaction was
      inhibited in the presence of zinc. Neq S has no catalytic activity and Neq L has
      lower 3'-->5' exonuclease activity; whereas Neq C and Neq P have polymerase and
      3'-->5' exonuclease activities, indicating that both Neq L and Neq S are needed
      to form the active DNA polymerase that possesses higher proofreading activity.
      The genetically protein splicing-processed Neq P showed the same properties as
      the protein trans-spliced Neq C. Our results are the first evidence to show
      experimentally that natural protein trans-splicing occurs in an archaeal protein,
      a thermostable protein, and a family B-type DNA polymerase.

PMID- 16412463
TI  - Cortisol/DHEA ratios in schizophrenia.

PMID- 16412464
TI  - Cerebrovascular reactivity following administration of mirtazapine in healthy
      probands--a randomized, placebo controlled double-blind clinical study.
AB  - INTRODUCTION: Cerebrovascular reactivity (CVR) reflects the compensatory dilatory
      capacity of cerebral arterioles to a dilatory stimulus and is important for
      maintaining constant cerebral blood flow. A reduced CVR increases the risk of
      stroke. We recently found that CVR was reduced in patients with depression. This
      might contribute to the higher risk of stroke that has been found in subjects
      suffering from depression. The characterization of pathophysiological conditions
      in the cerebral circulation requires the knowledge of influencing factors on CVR.
      We therefore investigated the influence that antidepressant administration might
      have on CVR in humans. METHODS: We investigated CVR in 48 healthy men before and
      after a 10-day application of either mirtazapine or placebo. CVR was determined
      by calculating the increase in cerebral blood flow velocity after stimulation
      with acetazolamide. Blood flow velocities were measured by transcranial Doppler
      ultrasound. RESULTS: There was no significant group-difference of CVR after the
      treatment trial compared to baseline. DISCUSSION: Mirtazapine does not seem to
      have an influence on CVR, or any impact on CVR might have been quickly limited by
      a cerebral autoregulatory response.

PMID- 16412465
TI  - Clinical characteristics of major depressive disorder run in families--a
      community study of 933 mothers and their children.
AB  - The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly
      demonstrated. Several studies have investigated associations between various
      clinical characteristics of MDD in probands and overall rates of MDD in
      relatives. Few studies, however, have considered the familial aggregation of
      clinical characteristics of MDD. The aim of the present report is to examine
      mother-offspring associations of a variety of clinical characteristics of MDD in
      a general population sample. Data were derived from baseline and 4-year-follow-up
      data of 933 adolescents and their biological mothers of the Early Developmental
      Stages of Psychopathology (EDSP) study, a prospective-longitudinal community
      study. MDD and its characteristics were assessed with the Munich-Composite
      International Diagnostic Interview. We found that children of mothers who had a
      lifetime history of severe MDD and high number of symptoms, high impairment
      and/or melancholia, revealed elevated odds of MDD regarding the same
      characteristics as their mothers (ORs between 5.2 and 13.9). The observed
      associations did not differ by the children's sex. DSM-IV melancholia and
      severity as well as impairment were found to aggregate within families. This
      finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as
      well as of the melancholic specifier. Severe and melancholic MDD reveal a
      considerable high degree of familiar aggregation making the search for mechanisms
      involved in the familiar transmission of these forms of MDD particularly
      promising.

PMID- 16412466
TI  - Gallbladder perforation: risk factors and outcome.
AB  - BACKGROUND: Gallbladder perforation is difficult to diagnose and is associated
      with significant morbidity. This study investigates factors affecting outcome in
      patients with gallbladder perforation over two decades. MATERIALS AND METHODS:
      From 1982 to 2002 data from patients undergoing cholecystectomy at one
      institution were prospectively collected. Patients treated for gallbladder
      perforation and gangrenous cholecystitis were identified and outcomes were
      compared. The chi(2) test, Student's t-test, and Mann-Whitney rank sum test were
      used for statistical analysis. RESULTS: Two hundred eight of 11,360 patients who
      underwent cholecystectomy were diagnosed with gangrenous cholecystitis and 30
      were diagnosed with gallbladder perforation. The perforation was contained in 9
      and free in 21 patients. The diagnosis of gallbladder perforation was made
      preoperatively in 3% of patients. Men outnumbered women and Hispanics outnumbered
      Caucasians. Compared to patients with gangrenous cholecystitis, patients with
      gallbladder perforation presented at an older age (53 versus 60 years; P < 0.05),
      had more cardiovascular comorbidity (29% versus 50%; P < 0.05) and postoperative
      complications (19% versus 37%; P < 0.05), and required more ICU admissions (9%
      versus 33%; P < 0.001) and longer hospital stays (8 versus 13 days; P < 0.001).
      Early cholecystectomy within 24 h improved outcome (P < 0.05). CONCLUSIONS:
      Gallbladder perforation is a rare complication of cholelithiasis that occurs more
      often in men, Hispanics, and older patients. It is rarely diagnosed
      preoperatively. Late operative intervention is associated with increased
      morbidity, mortality, number of ICU admissions, and long postoperative hospital
      stays. An early cholecystectomy strategy may lead to improved outcomes but may be
      difficult to implement and may not be cost-effective.

PMID- 16412467
TI  - TNF-alpha neutralization decreases nuclear factor-kappaB activation and apoptosis
      during renal obstruction.
AB  - BACKGROUND: Obstruction of the upper urinary tract is an important cause of
      progressive renal injury in children. While tumor necrosis factor-alpha (TNF
      alpha) and nuclear factor kappaB (NFkappaB) have independently been implicated in
      the pathophysiology of this process, TNF-alpha's role in obstruction-induced
      NFkappaB activation has not previously been investigated. MATERIALS AND METHODS:
      To study this, male Sprague Dawley rats were subjected to 3 days of unilateral
      ureteral obstruction (UUO) versus sham operation. Twenty-four hours prior to
      surgery and 2 days after, rats received either a vehicle or a pegylated form of
      soluble TNF receptor type 1 (PEG-sTNFR1). The kidneys were harvested 3 days
      postoperatively, and tissue samples were analyzed for TNF-alpha expression
      (ELISA), NFkappaB activation (EMSA, immunohistochemistry), IkappaB degradation
      (Western blot), angiotensinogen expression (Western blot), and apoptosis (TUNEL).
      RESULTS: Renal cortical TNF-alpha levels, NFkappaB activation, IkappaB
      degradation, angiotensinogen expression, and apoptotic cell death were
      significantly increased in response to obstruction. In contrast, TNF-alpha
      neutralization significantly reduced obstruction-induced TNF-alpha production,
      NFkappaB activation, IkappaB degradation, angiotensinogen expression, and renal
      tubular cell apoptosis. CONCLUSION: TNF-alpha's potent pro-inflammatory and
      cytotoxic effect during renal obstruction is directed through NFkappaB activation
      via increased IkappaB-alpha phosphorylation. As the role of TNF-alpha and
      NFkappaB in renal obstruction are further defined, the development of therapeutic
      strategies that limit or prevent obstruction-induced renal injury may be
      realized.

PMID- 16412468
TI  - The effect of polypropylene mesh on ilioinguinal nerve in open mesh repair of
      groin hernia.
AB  - OBJECTIVES: Repair of groin hernia is one of the most common operations performed
      by general surgeons, and mesh repair methods have gained wide acceptance. Chronic
      pain is the most serious long-term complication that can occur after repair of
      groin hernia. The development of chronic pain after herniorraphy has been
      attributed to several mechanisms, including damage to sensory nerves and mesh
      inguinodynia. MATERIAL AND METHODS: Twenty-four rabbits underwent bilateral
      inguinal dissection and synthetic polypropylene mesh laid on one side. Bilateral
      inguinal dissection was performed again after 3 months, and samples of nerve
      tissue were taken from both sides for histological examination. RESULTS: Light
      microscopic examination of the sections of control group peripheral nerves were
      in normal appearance, but the nerve fascicles in experimental group operated with
      mesh showed axonal dilation and mild-to-severe loss of myelinated axons.
      Examination of semi-thin and ultra-thin sections in control group peripheral
      nerve fascicles showed normal morphology. Ultrastructural nerve morphology in
      experimental group operated with mesh exhibited endoneurinal edema with
      thickening of both endoneurium and perineurium, causing separation of nerve
      fibers. Myelin sheaths of fibers showed an ondulation toward the axoplasm and the
      endoneurium. Separation of myelin layers from each other as a prominent feature
      of myelin degeneration in nerve fibers was also observed. Axoplasms exhibited
      edema and crystallization. CONCLUSIONS: The light microscopic and ultrastructural
      changes seen in peripheral nerves in experimental group operated with mesh
      suggested that mechanical compression of peripheral nerves is associated with
      myelin degeneration, endoneurinal and perineurial edema, fibrosis, axonal loss,
      and edema that may cause peripheral neuropathy. Chronic groin pain after hernia
      repair can be possibly caused by the entrapment of peripheral nerves in the scar
      tissue formed by the mesh.

PMID- 16412469
TI  - The functional integrity of a normothermic perfusion system using artificial
      blood in pig liver.
AB  - BACKGROUND: We have reported already that we succeeded in developing a
      normothermic liver perfusion system consisting of purely artificial products such
      as artificial blood. The aim of this study was to ascertain the metabolic
      functional integrity of the liver perfused in this system. MATERIALS AND METHODS:
      A liver graft from a female pig weighing 20 kg was harvested in the usual manner.
      The perfusion solution consisted of artificial blood, L-15 medium, distilled
      water, bovine serum albumin, NaHCO3, NaOH, KCl, human regular insulin, 50%
      glucose solution, and dexamethasone. The isolated liver was perfused with this
      oxygenated perfusate through the portal vein at a rate of 300 ml/min for 9 h. We
      analyzed the changes of amino acids, ammonia, and urea concentrations in five
      livers, which showed high oxygen consumption (over 8 ml-O2/min during perfusion).
      RESULTS: Although urea did not exist in the perfusate at first, an extremely high
      level of the urea concentration appeared during the perfusion. On the other hand,
      the ammonia concentration was only slightly elevated during the perfusion.
      Arginine vanished from the perfusate with increases of citrulline and ornithine.
      Taurine was elevated with the disappearance of methionine. Alanine, glutamine,
      serine, histidine, and threonine concentrations decreased with an increase of the
      glucose concentration. Numerous liver cells exhibited PAS-positive cytoplasmic
      glycogen deposits not exhibited before perfusion. The ratios of branched-chain
      amino acids/aromatic amino acids were elevated during the perfusion. CONCLUSION:
      Normothermic liver perfusion using artificial blood could sufficiently maintain
      the functional integrity of the liver.

PMID- 16412471
TI  - Influence of resident and attending surgeon seniority on operative performance in
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Resident participation in laparoscopic cholecystectomy (LC) is
      important for education but increases the time of operation. This time cost in
      training programs is not well-defined, and available data show no decrease in
      operative time as residents progress in training. We undertook this study to
      determine the effect of the resident and attending surgeon seniority on the
      operative performance of LC. PATIENTS AND METHODS: We undertook a retrospective
      review of LCs performed for all indications over two academic years in our
      training program. Operations were performed by junior (PGY 1-3) or senior (PGY 4
      5) residents, assisted by junior (trained after 1994) or senior attending
      surgeons, none of whom had fellowship training in advanced laparoscopy.
      Demographics, surgeon, assistant, operative time, and operative complications
      were recorded. Operative diagnoses were defined as noninflammatory (biliary
      colic, dyskinesia, or polyps) or inflammatory (cholecystitis, pancreatitis). The
      primary outcome was time in minutes from skin incision to closure; secondary
      outcomes were complications and conversions to laparotomy. ANOVA, Student's t
      test, and chi2 tests were used as appropriate with statistical significance
      attributed to P < 0.05. RESULTS: Three hundred fifteen LCs were performed. Two
      hundred seventy were without conversion to laparotomy or intraoperative
      cholangiography and were included in time and complication analysis. Junior
      attendings averaged 4 and senior attendings averaged 21 postresidency years. No
      differences were found on univariate analysis between groups in demographics or
      diagnosis category. Operative times were longer for junior residents irrespective
      of attending seniority: Jr Res/Jr Staff (n = 65): 86 +/- 32 min; Jr/Sr (n = 78):
      88 +/- 38 min; Sr/Jr (n = 52): 73 +/- 27 min; Sr/Sr (n = 75): 67 +/- 24 min (P <
      0.05). The overall rate of operative complications was higher in junior than
      senior resident cases (5.6% versus 0.78%, P < 0.05). The most common complication
      was cystic duct leak, of which 4/5 occurred in junior resident cases. Senior
      attendings had a trend toward increased conversions (8.4% versus 3.7%, P = 0.09).
      CONCLUSION: Resident, but not attending surgeon, seniority influences operative
      time and complication rate in LC. This information may help surgical educators
      maximize both resident learning and operative efficiency and safety.

PMID- 16412470
TI  - The effects of N-acetylcysteine on antioxidant enzyme activities in experimental
      testicular torsion.
AB  - Testicular torsion is a serious problem in male children and, if not treated at
      the right time, can lead to subfertility and infertility. The main reason for
      testicular damage is ischemia-reperfusion injury. A number of chemical substances
      have been used to protect testes against ischemia-reperfusion injury in
      experimental animals. The possible protective effect of N-acetylcysteine on
      testicular tissue after testicular detorsion was examined in the current study.
      Twenty-four rats were divided into four groups: sham operation, torsion,
      detorsion, and NAC + detorsion groups (n = 6 for each group). Excluding sham
      operation group, the rats were subjected to unilateral torsion (720-degree
      rotation in clockwise direction). After torsion (5 h) and detorsion (2 h),
      unilateral orchidectomy was performed. Malondialdehyde levels and superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase activities
      were determined in testicular tissue. Administration of N-acetylcysteine caused a
      decrease in malondialdehyde levels and an increase in glutathione peroxidase
      levels compared to detorsion group. The results suggest that N-acetylcysteine may
      be a potential protective agent for preventing the negative biochemical changes
      related to oxidative stress in testicular injury caused by testis torsion.

PMID- 16412472
TI  - Intracoronary shunt-induced endothelial cell damage in porcine heart.
AB  - BACKGROUND: Injury to and dysfunction of the endothelium can compromise the
      patency of coronary arteries and lead to impaired perfusion of the heart. Such
      injury can occur after the application of an intravascular shunt and/or a snare
      to a coronary artery during bypass surgery. In this study, multiphoton microscopy
      was used to assess the integrity of endothelium in porcine coronary arteries
      subjected to shunting and snaring during off-pump coronary artery bypass grafting
      (OPCAB). MATERIALS AND METHODS: In open chest porcine, the left anterior
      descending artery was manipulated in different regions using snare and shunt to
      simulate OPCAB. Sections of left anterior descending artery were labeled with
      fluorescent dyes to evaluate the viability of the endothelium. The structural
      integrity of the endothelium was evaluated by calcein- and ethidium homodimer
      mediated fluorescence. Endothelial functional viability was assessed by measuring
      cellular esterase activity, calcium mobilization, and endothelial nitric oxide
      synthase-mediated generation of nitric oxide using fluorescence dyes and
      multiphoton microscopy. RESULTS: Substantial endothelial damage was observed in
      shunted region of the coronary arteries. In contrast, endothelium remained
      structurally viable in regions that were snared, similar to control regions of
      the coronary arteries that were not manipulated. Esterase activity, calcium
      mobilization, and nitric oxide generation was greater in the control and snared
      regions of the coronary arteries in comparison to the shunted region.
      CONCLUSIONS: The use of intracoronary shunts led to structural damage and
      attenuation of endothelial function in porcine coronary arteries, whereas snared
      vessels maintained their viability and integrity, similar to the control
      sections. The routine use of shunts in OPCABG may lead to endothelial damage and
      possibly to long-term graft failure.

PMID- 16412473
TI  - Parameters associated with changes in liver volume in patients undergoing portal
      vein embolization.
AB  - BACKGROUND: To identify predictors of changes in hepatic volumes after portal
      vein embolization (PVE) before hepatectomy, we examined the relationship between
      clinicopathological parameters and changes in volume of embolized and
      nonembolized liver and regeneration of remnant liver after hepatectomy. MATERIALS
      AND METHODS: The subjects were 25 patients who underwent laparotomy. PVE was
      performed through transileocolic vein (n = 15) and percutaneous transhepatic
      puncture (n = 10). RESULTS: Significant atrophy and hypertrophy of the embolized
      and nonembolized liver were observed after PVE, respectively, and further
      increase of remnant liver volume was observed after hepatectomy. Background liver
      disease did not seem to influence the results. Alkaline phosphatase (ALP) level
      correlated negatively with atrophy of embolized lobe (r = -0.433). Platelet count
      correlated positively with hypertrophy of nonembolized lobe (r = 0.412, P < 0.05)
      and percent increase between lobes and (r = 0.515, P < 0.05). Seven (32%)
      patients developed postoperative complications, such as long-term ascites or
      cholestasis. Changes in embolized liver and percent increase between lobes in
      patients with postoperative cholestasis (-94 +/- 97 cm(3) and 9.6 +/- 5.1% gain)
      were significantly lower than those in patients without cholestasis (17 +/- 54
      cm(3) and 6.6 +/- 1.3% gain, P < 0.05). CONCLUSION: ALP and platelet counts might
      be able to predict PVE effect and were related to postoperative course.
      Identification of more specific predictors is desirable.

PMID- 16412474
TI  - Electrophysiologic techniques in critical illness-associated weakness.
AB  - Neuromuscular disorders are increasingly recognized in the critically ill but
      conventional electrodiagnostic techniques often provide non-specific results or
      are hampered by local conditions that prevent adequate disease classification.
      Muscle fiber inexcitability is a common phenomenon in critical illness myopathy
      possibly secondary to disordered sodium channel fast inactivation and associated
      with loss of myosin staining. Direct muscle stimulation techniques, measuring
      evoked response amplitudes and comparison of nerve and muscle stimulated
      responses, are recognized methods of demonstrating this phenomenon. Other
      measures studied in this population include increased compound motor action
      potential duration, motor unit number estimates and mean step area of individual
      motor unit potentials during motor unit number estimate studies. An
      electrophysiologic approach to the study of patients with critical illness
      associated weakness is proposed.

PMID- 16412475
TI  - Catalyst-induced growth with limited catalyst lifespan and competition.
AB  - Spatially extended catalyst-induced growth processes are studied. This type of
      processes exists in all domains of biology, ranging from ecology (nutrients and
      growth), through immunology (antigens and lymphocytes) to molecular biology
      (signaling molecules initiating signaling cascades). The extinction-proliferation
      transition is considered for a system containing discrete catalysts (A) that
      induces the proliferation of a discrete reactant (B). The realization of this
      model on an infinite capacity d-dimensional discrete lattice for immortal
      catalysts has been previously considered (the AB model). It was shown that the
      adaptation of the reactants to the diffusive noise induced by stochastic
      fluctuations of catalyst density yields proliferation even if the average
      environmental conditions lead to extinction. This model is extended here to
      include more realistic situations, like finite lifespan of the catalysts and
      finite carrying capacity of the reactants. By using a combination of Monte Carlo
      simulation, percolation-theory-based estimations and an analytic perturbative
      analysis, the asymptotic behavior of these systems is studied. In both cases
      studied, it turns out that the overall survival of the reactant population at the
      long run is based on the size and shape of a typical single colony, related to
      the localized proliferation around spatio-temporal catalyst density fluctuations.
      If the density of these colonies (based on the lifetime of the spatial
      fluctuation and the carrying capacity of the medium) is large enough, i.e. above
      the percolation threshold, the reactant population survives even in (on average)
      hostile environment. This model provides a new insight on the population dynamics
      in chemical, biological and ecological systems.

PMID- 16412476
TI  - C-reactive protein induced expression of adhesion molecules in cultured cerebral
      microvascular endothelial cells.
AB  - Ischemic stroke can trigger an acute phase response resulting in a rise of plasma
      concentration of C-reactive protein (CRP). Clinical data about the relationship
      between CRP and prognosis suggest that CRP might be involved in the pathogenesis
      of cerebral ischemia. In the present work, a significant increase of circulating
      level of CRP was observed in an vivo rat brain ischemia model of middle cerebral
      artery occlusion. To determine the possible effects of CRP on brain microvessel
      endothelium, we performed a dose-dependent experiment in mouse brain
      microvascular endothelial cells (bEnd.3 cells) with emphasis on its relation to
      cell adhesions molecules. Incubation with CRP (1-75 mg/L) for 24 h significantly
      increased Lactate dehydrogenase (LDH) leakage from bEnd.3 cells (P<0.01) in a
      dose-dependent manner, and induced significant up-regulations of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)
      expressions analyzed by Western blotting (P<0.01). In contrast to earlier report,
      CRP also induced significant increase in ICAM-1 expression in the absence of
      serum (P<0.01). In conclusion, the present results suggest that CRP may be
      involved directly in the development of inflammation in response to cerebral
      ischemia.

PMID- 16412477
TI  - Orange juice increased the bioavailability of pravastatin, 3-hydroxy-3
      methylglutaryl CoA reductase inhibitor, in rats and healthy human subjects.
AB  - Our objective was to investigate the effects of orange juice on the
      pharmacokinetics of pravastatin in rats and healthy volunteers. The
      pharmacokinetics of pravastatin (100 mg/kg p.o.) were assessed with water, orange
      juice, and carbohydrates (12.5 ml/kg over 30 min) and with acetic acid (0.1 M, pH
      3.44). The pharmacokinetics of simvastatin (100 mg/kg p.o.) were assessed with
      water and orange juice. In addition, the pharmacokinetics (based on plasma
      levels) of pravastatin 80 mg/kg i.v. were assessed with water and orange juice (5
      ml/kg) in rats. The pharmacokinetics of oral pravastatin (10 mg) were assessed
      when administered with water and orange juice (800 ml over 3 h) in a two-way
      crossover study in 14 healthy volunteers. Orange juice significantly increased
      the area under the curve (0-150 min) of pravastatin in rats. Orange juice had no
      effects on the pharmacokinetic parameters of intravenously administered
      pravastatin in rats. Carbohydrates and acetic acid with pH and concentration
      equivalent to those of orange juice also resulted in no statistically significant
      differences in pravastatin pharmacokinetic parameters in rats. Orange juice did
      not result in any significant differences in the pharmacokinetic parameters of
      simvastatin in rats. Orange juice significantly increased oatp1 and oatp2 mRNA
      and protein in the intestine of rats. Orange juice significantly increased the
      area under the curve (0-240 min) of pravastatin in healthy volunteers. In
      conclusion, orange juice increases the bioavailability of pravastatin
      administered orally. Oatp1 and oatp2 may be related to increases of
      pharmacokinetics of pravastatin by orange juice.

PMID- 16412478
TI  - A signal-to-noise analysis of phylogeny estimation by neighbor-joining:
      Insufficiency of polynomial length sequences.
AB  - Phylogeny reconstruction is the process of inferring evolutionary relationships
      from molecular sequences, and methods that are expected to accurately reconstruct
      trees from sequences of reasonable length are highly desirable. To formalize this
      concept, the property of fast-convergence has been introduced to describe
      phylogeny reconstruction methods that, with high probability, recover the true
      tree from sequences that grow polynomially in the number of taxa n. While
      provably fast-converging methods have been developed, the neighbor-joining (NJ)
      algorithm of Saitou and Nei remains one of the most popular methods used in
      practice. This algorithm is known to converge for sequences that are exponential
      in n, but no lower bound for its convergence rate has been established. To
      address this theoretical question, we analyze the performance of the NJ algorithm
      on a type of phylogeny known as a 'caterpillar tree'. We find that, for sequences
      of polynomial length in the number of taxa n, the variability of the NJ criterion
      is sufficiently high that the algorithm is likely to fail even in the first step
      of the phylogeny reconstruction process, regardless of the degree of polynomial
      considered. This result demonstrates that, for general n-taxa trees, the
      exponential bound cannot be improved.

PMID- 16412479
TI  - The effect of melanin on the bystander effect in human keratinocytes.
AB  - The influence of melanin on radiation-induced bystander effects has been studied.
      Melanin is known to be a natural substance with proved radioprotective properties
      in different organisms and cell lines. It is non-toxic and is effective against
      acute and chronic irradiation. The lower the radiation dose, the higher the
      relative impact of melanin protection. In this study influence of melanin on
      human keratinocytes (HPV-G cells) has been studied using the colony-forming
      assay. We have shown that bystander donor medium from 0.5 Gy irradiated cells
      when transferred to unirradiated cells, caused almost the same effect as direct
      irradiation. Melanin increased the colony-forming ability of bystander recipient
      cells when it was added into culture medium before irradiation. The effect of
      melanin added after irradiation was to produce less protection in both the
      directly irradiated and bystander medium treated groups. The absorption spectrum
      of the filtered medium is identical to one of the intact culture medium showing
      that melanin was not present in filtered medium. Thus, it cannot protect
      recipient cells but reduces the amount of the bystander effect. It is concluded
      that melanin added before irradiation effectively decreased the radiation dose.
      The reduction of the impact of the bystander signal on recipient cells when
      melanin was added to the donor medium after harvest but before filtration, may
      mean that the bystander signal has a physical component as melanin can absorb all
      types of physical energy.

PMID- 16412480
TI  - Expression of D2 receptor isoforms in cultured neurons reveals equipotent
      autoreceptor function.
AB  - Alternative splicing of the dopamine D2 receptor gene produces two distinct
      isoforms referred to as D2long (D2L) and D2short (D2S). In mesencephalic dopamine
      neurons, inhibition of the firing rate through activation of somatodendritic D2
      receptors and blockade of neurotransmitter release through stimulation of
      terminal D2 receptors represent major roles of D2 autoreceptors. Recently, data
      obtained from D2L-deficient mice suggested that D2S acts as the preferential D2
      autoreceptor. In the present study, we investigate whether this D2 isoform
      specific autoreceptor function is linked to differences in the subcellular
      localization and/or signaling properties of the D2S and D2L using mesencephalic
      neurons transfected with enhanced green fluorescent protein (EGFP)-tagged
      receptors. Our results show that EGFP-tagged D2S and D2L are localized to the
      axonal and somatodendritic compartments of mesencephalic neurons. In addition, we
      demonstrate that EGFP-tagged D2S and D2L regulate cellular excitability,
      neurotransmitter release and basal levels of intracellular calcium with similar
      effectiveness. Overall, our morphological and electrophysiological studies
      suggest that the major D2 autoreceptor function attributed to D2S is likely
      explained by the predominant expression of this isoform in dopamine neurons
      rather than by distinct subcellular localization and signaling properties of D2S
      and D2L.

PMID- 16412481
TI  - Disinhibition of spinal responses to primary afferent input by antagonism at GABA
      receptors in urethane-anaesthetised rats is dependent on NMDA and metabotropic
      glutamate receptors.
AB  - Disruption of spinal GABAergic circuits, which regulate the conveyance of sensory
      information to spinal cord neurones from the primary afferent system, leads to
      miscoding of afferent input and often results in hyperresponsiveness states. In
      the present work, extracellular field potentials elicited by electrical
      peripheral nerve activation were recorded in the urethane-anaesthetised rat
      following spinal administration of GABA(A) or GABA(B) receptor-antagonists, and
      the involvement of glutamate receptors of the NMDA and metabotropic types in
      changes induced by altered GABAergic function was examined by pre-treating the
      spinal dorsal horn with appropriate antagonist drugs. Spinal administration of
      the GABA(A) receptor antagonist bicuculline (BIC) dose-dependently augmented poly
      but not monosynaptic field potentials elicited by activation of A fibres or
      potentials elicited by activation of C fibres, whereas application of the GABA(B)
      receptor antagonist CGP35348 significantly increased the amplitudes of C- but not
      A fibre-evoked potentials. BIC-induced augmentation was blocked by pre-treatment
      with the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5)
      or the group I or II metabotropic glutamate receptor (mGluR)-antagonists (RS)-1
      aminoindan-1,5-dicarboxylic acid (AIDA) or (2S)-alpha-ethylglutamic acid (EGLU),
      respectively, but not by the group III mGluR-antagonist (RS)-alpha-methylserine-O
      phosphate (MSOP). Augmentation of spinal field potentials induced by CGP35348 was
      prevented by pre-treatment with D-AP5 but not with mGluR-antagonists. The present
      findings provide novel evidence that disparate synaptic mechanisms subserved by
      metabotropic and NMDA glutamate receptors may be involved in spinal
      hyperresponsiveness states secondary to decreased GABA(A) or GABA(B) receptor
      activity.

PMID- 16412482
TI  - Depolarization and Ca(2+) down regulate CB1 receptors and CB1-mediated signaling
      in cerebellar granule neurons.
AB  - Presynaptic terminals of cerebellar granule neurons are primary targets of
      cannabinoids, which act through type 1 G alpha(i/o)-coupled cannabinoid receptors
      (CB1) to modulate glutamate release. To study CB1 signaling investigators use
      primary cultures of granule neurons, typically grown in medium supplemented with
      elevated KCl to improve long-term survival. Herein, we demonstrate that CB1
      expression and signaling are perturbed under these conditions. Specifically,
      immunochemical and RT-PCR assays indicate that depolarizing growth conditions
      decrease CB1 protein, mRNA and CB1-mediated inhibition of adenylyl cyclase
      compared to cultures grown in physiologic medium containing 5mM KCl.
      Depolarization-dependent downregulation of CB1 mRNA, like survival, is attenuated
      by L-type VDCC antagonists but not the Na(+)-channel antagonist, tetrodotoxin.
      Comparison of oligonucleotide microarrays from cultures grown in 5mM versus 25 mM
      KCl confirms that depolarization reduces CB1 mRNA, but not mRNAs encoding several
      G-protein subunits or adenylyl cyclases. However, significant alterations in
      synaptic signaling proteins that likely lie downstream of CB1 are observed,
      including K(+) channels, alpha-neurexins, cAMP-GEFII, Munc13-3, secretogranin and
      synaptotagmin. These findings make a compelling argument to adopt cultures grown
      in 5mM KCl for future study of CB1 signaling in granule neurons. Further, they
      suggest that a depolarization and Ca(2+)-dependent signaling pathway represses
      CB1 gene transcription.

PMID- 16412483
TI  - The rise, fall, and resurrection of the ventromedial hypothalamus in the
      regulation of feeding behavior and body weight.
AB  - Early researchers found that lesions of the ventromedial hypothalamus (VMH)
      resulted in hyperphagia and obesity in a variety of species including humans,
      which led them to designate the VMH as the brain's "satiety center." Many
      researchers later dismissed a role for the VMH in feeding behavior when Gold
      claimed that lesions restricted to the VMH did not result in overeating and that
      obesity was observed only with lesions or knife cuts that extended beyond the
      borders of the VMH and damaged or severed the ventral noradrenergic bundle (VNAB)
      or paraventricular nucleus (PVN). However, anatomical studies done both before
      and after Gold's study did not replicate his results with lesions, and in nearly
      every published direct comparison of VMH lesions vs. PVN or VNAB lesions, the
      group with VMH lesions ate substantially more food and gained twice as much
      weight. Several other important differences have also been found between VMH and
      both PVN and VNAB lesion-induced obesity. Concerns regarding (a) motivation to
      work for food and (b) the effects of nonirritative lesions have also been
      addressed and answered in many studies. Lesion studies with weanling rats and
      adult pair-tube-fed rats, as well as recent studies of knockout mice deficient in
      the orphan nuclear receptor steroidogenic factor 1, indicate that VMH lesion
      induced obesity is in large part a metabolic obesity (due to autonomic nervous
      system disorders) independent of hyperphagia. However, there is ample evidence
      that the VMH also plays a primary role in feeding behavior. Neuroimaging studies
      in humans have shown a marked increase in activity in the area of the VMH during
      feeding. The VMH has a large population of glucoresponsive neurons that
      dynamically respond to blood glucose levels and numerous histamine, dopamine,
      serotonin, and GABA neurons that respond to feeding-related stimuli. Recent
      studies have implicated melanocortins in the VMH regulation of feeding behavior:
      food intake decreases when arcuate nucleus pro-opiomelanocortin (POMC) neurons
      activate VMH brain-derived neurotrophic factor (BDNF) neurons. Moderate
      hyperphagia and obesity have also been observed in female rats with damage to the
      efferent projections from the posterodorsal amygdala to the VMH. Hypothalamic
      obesity can result from damage to either the POMC or BDNF neurons. The concept of
      hypothalamic feeding and satiety centers is outdated and unnecessary, and
      progress in understanding hypothalamic mechanisms of feeding behavior will be
      achieved only by appreciating the different types of neural and blood-borne
      information received by the various nuclei, and then attempting to determine how
      this information is integrated to obtain a balance between energy intake and
      energy output.

PMID- 16412484
TI  - Acetylated flavonol diglucosides from Meconopsis quintuplinervia.
AB  - Four acetylated flavonol diglucosides, quercetin 3-O-[2'''-O-acetyl-beta-d
      glucopyranosyl-(1-->6)-beta-d-glucopyranoside], quercetin 3-O-[2''',6'''-O
      diacetyl-beta-d-glucopyranosyl-(1-->6)-beta-d-glucopyranoside], isorhamnetin 3-O
      [2'''-O-acetyl-beta-d-glucopyranosyl-(1-->6)-beta-d-glucopyranoside], and
      quercetin 3-O-[2'''-O-acetyl-alpha-l-arabinopyranosyl-(1-->6)-beta-d
      glucopyranoside], together with five known flavonol glycosides quercetin 3-O-beta
      d-glucopyranoside, kaempferol 3-O-beta-d-glucopyranoside, quercetin 3-O-[beta-d
      galactopyranosyl-(1-->6)-glucopyranoside], isorhamnetin 3-O-[beta-d
      galactopyranosyl-(1-->6)-beta-d-glucopyranoside], and kaempferol 3-O-[beta-d
      glucopyranosyl-(1-->2)-beta-d-glucopyranoside] have been isolated from Meconopsis
      quintuplinervia. Their structures were determined using chemical and
      spectroscopic methods including HRFABMS, (1)H-(1)H COSY, HSQC and HMBC
      experiments.

PMID- 16412485
TI  - Flavonoid 3'-O-methyltransferase from rice: cDNA cloning, characterization and
      functional expression.
AB  - Plant O-methyltransferases (OMTs) are known to be involved in methylation of
      plant secondary metabolites, especially phenylpropanoid and flavonoid compounds.
      An OMT, ROMT-9, was cloned and characterized from rice using a reverse
      transcriptase polymerase chain reaction (RT-PCR). The blast results for ROMT-9
      showed a 73% identity with caffeic acid OMTs from maize and Triticum aestivum.
      ROMT-9 was expressed in Escherichia coli and its recombinant protein was purified
      using affinity chromatography. It was then tested for its ability to transfer the
      methyl group of S-adenosyl-l-methionine to the flavonoid substrates, eriodictyol,
      luteolin, quercetin, and taxifolin, all of which have a 3'-hydroxyl functional
      group. The reaction products were analyzed using TLC, HPLC, HPLC/MS, and NMR
      spectroscopy. The NMR analysis showed that ROMT-9 transferred the methyl group
      specifically to the 3'-hydroxyl group of quercetin, resulting in the formation of
      its methoxy derivative. Furthermore, ROMT-9 converted flavonoids containing the
      3'-hydroxy functional group such as eriodictyol, luteolin, quercetin and
      taxifolin into the corresponding methoxy derivatives, suggesting that ROMT-9 is
      an OMT with strict specificity for the 3'-hydroxy group of flavonoids.

PMID- 16412486
TI  - Identifying the biting species in snakebite by clinical features: an
      epidemiological tool for community surveys.
AB  - The outcome of snakebite is related to the biting species but it is often
      difficult to identify the biting snake, particularly in community settings. We
      have developed a clinical scoring system suitable for use in epidemiological
      surveys, with the main aim of identifying the presumed biting species in those
      with systemic envenoming who require treatment. The score took into account ten
      features relating to bites of the five medically important snakes in Sri Lanka,
      and an algorithm was developed applying different weightings for each feature for
      different species. A systematically developed artificial data set was used to
      fine tune the score and to develop criteria for definitive identification. The
      score was prospectively validated using 134 species-confirmed snakebites. It
      correctly differentiated the bites caused by the three snakes that commonly cause
      major clinical problems (Russell's viper (RV), kraits and cobra) from other
      snakes (hump-nosed viper (HNV) and saw-scaled viper (SSV)) with 80% sensitivity
      and 100% specificity. For individual species, sensitivity and specificity were,
      respectively: cobra 76%, 99%; kraits 85%, 99%; and RV 70%, 99%. As anticipated,
      the score was insensitive in the identification of bites due to HNV and SSV.

PMID- 16412487
TI  - A new eriophyid mite-borne membrane-enveloped virus-like complex isolated from
      plants.
AB  - A decade ago, a new mite-transmitted disease was described on wheat (Triticum
      aesativum) and maize (Zea mays) that due to its geographical location was
      referred to as High Plains Disease (HPD). To determine the etiology, we
      established colonies of HPD pathogen-transmitting eriophyid wheat curl mites
      (Aceria tosichella) on wheat plants for maintenance of a continuous source of
      infected material. Analyses of nucleic acid obtained from infected plants showed
      the presence of HPD-specific RNAs ranging from 1.5 to 8 kilobases, but
      comparisons between the sequence of cDNAs and the databases did not reveal any
      clear identity with known viruses. We demonstrate that a diagnostic HPD-specific
      32-kDa protein that accumulates in plants is encoded by a small RNA species (RNA
      s). Upon infestation of upper wheat parts with viruliferous mites, the RNA-s
      encoded protein becomes detectable within a few days in the roots, indicative of
      an effective virus-like mode of transport. Membranous particles, resembling those
      observed in thin sections of infected plants, were isolated and shown to envelope
      a thread-like ribonucleoprotein complex containing the RNA-s encoded 32-kDa
      protein. This complex was associated with single-stranded (-)-sense RNAs, whereas
      free (+)-sense RNA was only detected in total RNA of infected plants. Based on
      the collective properties, we conclude that HPD is caused by a newly emerged mite
      borne virus, for which we propose the name Maize red stripe virus (MRStV).

PMID- 16412489
TI  - Abortive replication of Bombyx mori nucleopolyhedrovirus in Sf9 and High Five
      cells: defective nuclear transport of the virions.
AB  - Despite close genetic relationship, Bombyx mori nucleopolyhedrovirus (BmNPV) and
      Autographa californica multicapsid NPV (AcMNPV) display a distinct host range
      property. Here, BmNPV replication was examined in Sf9 and High Five cells that
      were nonproductive for BmNPV infection but supported high titers of AcMNPV
      replication. Recombinant BmNPV, vBm/gfp/lac, containing bm-ie1 promoter-driven
      egfp showed that few Sf9 and High Five cells infected with vBm/gfp/lac expressed
      EGFP, while large proportion of EGFP-expressing cells was observed when
      transfected with vBm/gfp/lac DNA. Immunocytochemical analysis showed that BmNPV
      was not imported into the nucleus of these two cell lines, while recombinant
      BmNPV, vBmDelta64/ac-gp64 possessing AcMNPV gp64 was imported into the nucleus,
      yielding progeny virions in High Five cells, but not Sf9 cells. These results
      indicate that the defective nuclear import of infected virions due to
      insufficient BmNPV GP64 function is involved in the restricted BmNPV replication
      in Sf9 and High Five cells.

PMID- 16412488
TI  - A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins.
AB  - The Yellow Fever Vaccine 17D (YFV17D) has been used as a vector for the Lassa
      virus glycoprotein precursor (LASV-GPC) resulting in construction of YFV17D/LASV
      GPC recombinant virus. The virus was replication-competent and processed the LASV
      GPC in cell cultures. The recombinant replicated poorly in guinea pigs but still
      elicited specific antibodies against LASV and YFV17D antigens. A single
      subcutaneous injection of the recombinant vaccine protected strain 13 guinea pigs
      against fatal Lassa Fever. This study demonstrates the potential to develop an
      YFV17D-based bivalent vaccine against two viruses that are endemic in the same
      area of Africa.

PMID- 16412490
TI  - Increased HIV-DNA load in CCR5-negative lymphocytes without viral phenotypic
      change.
AB  - We have previously described a selective increase in HIV-DNA content in CCR5
      negative lymphocytes from late stage HIV-infected patients. Here, we show that
      this increase occurred even in the absence of viral phenotypic switching from
      CCR5- to CXCR4-tropic. This leads us to hypothesize that early and late CCR5
      tropic viruses might be different in the ability to infect CCR5-low or -negative
      cells. We compared a set of early CCR5-tropic viruses with low viral DNA content
      in CCR5-negative cells to a set of late CCR5-tropic viruses with high viral DNA
      content in CCR5-negative cells. We could not find any significant differences
      between the two sets of viruses in the aspects of relative infectivity in CCR5
      low cells and the level of inhibition by beta-chemokine. This suggested that
      there may be some changes in cellular phenotype or environment that allows an
      expansion of susceptible cell population in late stages HIV infection.
      Understanding these changes may provide a novel approach for HIV therapy.

PMID- 16412491
TI  - Modeling the sensitivity to variability relationship in perimetry.
AB  - PURPOSE: Studies in glaucoma patients show that standard automated perimetry
      results increase in variability as sensitivity decreases. However, the reasons
      for this change are unclear. This study presents the principle of Divergent
      Dysfunction as a possible explanation for this change in variability, and
      incorporates it into a model that can be used to simulate perimetry. METHODS: A
      computer program was written to simulate visual field test results based on the
      model, using a Full Threshold testing strategy. The validity of the simulation
      was tested by comparing it with normal sensitivity values, and with test-retest
      data from 63 participants evaluated five times each over the course of 1 month.
      The effect on the simulated data of varying parameters of the model was
      investigated, such as changing the magnitude of variability and the percentages
      of false positive and negative responses. RESULTS: The correlation between
      subject and simulated test-retest data was 0.987. Several factors were found to
      affect the sensitivity-variability relationship for the simulated data, most
      notably the rate of sensitivity decline, the percentage of false positives, and
      the starting luminance of the test procedure. CONCLUSIONS: The principle of
      Divergent Dysfunction presented here provides a plausible explanation for the
      sensitivity-variability relationship for standard automated perimetry in
      glaucomatous eyes. The model and resultant simulation program aim to provide an
      intuitive demonstration of the principle, which can also be used to examine the
      effectiveness of different testing strategies. These findings have great
      implications for future clinical research.

PMID- 16412492
TI  - Stereo and motion information are not independently processed by the visual
      system.
AB  - Many visual tasks are carried out by using multiple sources of sensory
      information to estimate environmental properties. In this paper, we present a
      model for how the visual system combines disparity and velocity information. We
      propose that, in a first stage of processing, the best possible estimate of the
      affine structure is obtained by computing a composite score from the disparity
      and velocity signals. In a second stage, a maximum likelihood Euclidean
      interpretation is assigned to the recovered affine structure. In two experiments,
      we show that human performance is consistent with the predictions of our model.
      The present results are also discussed in the framework of another theoretical
      approach of the depth cue combination process termed Modified Weak Fusion.

PMID- 16412493
TI  - Relationship between chlorine consumption and chlorination by-products formation
      for model compounds.
AB  - The objective of this research is to investigate the relationship between
      chlorine decay and the formations of disinfection by-products (DBP), including
      trichloromethane (TCM) and chloroacetic acid (CAA) in the presence of four model
      compounds, i.e., resorcinol, phloroglucinol, p-hydroxybenzoic acid, and m
      hydroxybenzoic acid. The chlorine degradation in model compounds with OH and/or
      COOH functional groups were rapid after chlorination. The TCM yields of
      carboxylic group substituted compounds (3-hydroxybenzoic acid [3-HBA], 4
      hydroxybenzoic acid [4-HBA]) were found to be lower than that of the m-dihydroxy
      substituted compounds. Phloroglucinol, with one more OH substitution group than
      resorcinol, tends to form significant amounts of CAA after chlorination. However,
      it was observed that with the COOH substitution of 3-HBA and 4-HBA tend to
      exhibit more CAA formation potential than resorcinol. The developed parallel
      second and first-order reaction model for chlorine demand has been successfully
      utilized for TCM, CAA and DBP formation modeling. A high correlation between CAA
      and TCM was observed for the model compounds.

PMID- 16412494
TI  - Photocatalytic degradation of mixed gaseous carbonyl compounds at low level on
      adsorptive TiO2/SiO2 photocatalyst using a fluidized bed reactor.
AB  - An adsorptive silica-supported titania photocatalyst TiO(2)/SiO(2) was prepared
      by using nanosized titania (anatase) immobilized on silica gel by the sol-gel
      technique with the titanium tetra isopropoxide as the main raw material and
      acetic acid as the acid catalyst. Meanwhile the structure and properties of the
      TiO(2)/SiO(2) photocatalyst were studied by means of many modern analysis
      techniques such as TEM, XRD, and BET. Gas-solid heterogeneous photocatalytic
      decomposition of four carbonyl compounds mixture at low concentration levels over
      ultraviolet irradiated TiO(2)/SiO(2) photocatalyst were carried out with high
      degradation efficiencies in a coaxial triple-cylinder-type fluidized bed
      photocatalytic reactor, which provided efficient continuous contact of
      ultraviolet photons, silica-supported titania photocatalyst, and gaseous
      reactants. Experimental results showed that the photocatalyst had a high
      adsorption performance and a good photocatalytic activity for four carbonyl
      compounds mixture. Some factors influencing the photocatalytic decomposition of
      the mixed carbonyl compounds, i.e. the gas flowrate, relative humidity,
      concentration of oxygen, and illumination time, were discussed in detail. It is
      found that the photocatalytic reaction rate of four carbonyl compounds decreased
      in this order: propionaldehyde, acetone, acetaldehyde and formaldehyde.

PMID- 16412495
TI  - Congener group patterns of chloroparaffins in marine sediments obtained by
      chloride attachment chemical ionization and electron capture negative ionization.
AB  - Congener group patterns of technical short chain and medium chain chloroparaffins
      (SCCP and MCCP) were determined by electron capture negative ionization (ECNI)
      and chloride attachment chemical ionization (CACI) mass spectrometry (MS). In
      contrast to CACI-MS, congener patterns obtained by ECNI showed always a shift to
      the next higher chlorinated congener and carbon chain length group. Consequently,
      the calculated molecular masses and chlorine contents were higher for ECNI
      (factor 1.10+/-0.03 and 1.09+/-0.03, respectively). ECNI/CACI ratios in sediment
      samples from the North and Baltic Sea were also slightly higher. However, a more
      pronounced shift of the congener pattern for a given carbon chain length to
      congeners with 2-3 more chlorine atoms was observed. SCCP and MCCP concentrations
      obtained by ECNI-MS were in the range of 8-63ngg(-1) (North Sea) and 22-149ngg(
      1) dry weight (Baltic Sea). MCCP levels were highest in all samples (MCCP/SCCP
      factor 1.1-3.2).

PMID- 16412496
TI  - High-resolution profiles of trace metals in the pore waters of riverine sediment
      assessed by DET and DGT.
AB  - The techniques of DET (diffusive equilibrium in thin films) and DGT (diffusive
      gradients in thin films) were applied to obtain high-resolution vertical profiles
      of trace metals in freshwater sediments. In the framework of the EU-Interreg
      project Stardust (http://www.vliz.be/projects/stardust/) between France and
      Belgium, in which the mobility of sediment bound metals is investigated, sediment
      samples were collected from the Upper Scheldt River (at Helkijn, Belgium) and the
      Leie River (at Warneton, located at the Belgian-French border). Intra- and inter
      laboratory comparisons of the gel techniques were carried out between the two
      laboratories involved. In general, a good agreement was observed, taking sediment
      heterogeneity into account. At both stations, metal pore water profiles show more
      or less similar tendencies although the sediment at Warneton was more anoxic than
      at Helkijn. A strong correlation between Fe and Co was found at Helkijn as well
      as at Warneton. The metal gradients at the water/sediment interface were
      calculated from the high resolution profiles and the conventional, low resolution
      profiles. Significant differences were observed.

PMID- 16412498
TI  - In vitro fibrin clot formation and fibrinolysis using heterozygous plasma
      fibrinogen from gammaAsn319, Asp320 deletion dysfibrinogen, Otsu I.
AB  - INTRODUCTION: We have reported a heterozygous dysfibrinogenemia, fibrinogen Otsu
      I, caused by the deletion of gammaAsn319 and gammaAsp320, which was originally
      identified in the dysfibrinogen Vlissingen/Frankfurt IV (V/FIV) associated with
      thrombosis. Unlike the V/FIV family, the Otsu propositus showed no thrombotic
      tendencies. To analyze the relationship between thrombosis and the heterozygous
      plasma variant fibrinogen, we used purified plasma fibrinogen from the Otsu
      patient and compared it with a normal control. MATERIALS AND METHODS: Thrombin
      induced fibrin clot formation and clot structure were observed by fibrin
      polymerization and scanning electron microscopy, respectively. For in vitro
      observation of fibrinolysis, plasmin generation and clot lysis assays were
      performed by the addition of tissue type plasminogen activation (tPA) and
      plasminogen. RESULTS AND CONCLUSIONS: Polymerization of Otsu was markedly
      impaired, while fibrin fibers were much thicker and the density of the bundles of
      fibrin fibers was less and porous compared with normal. Lysis of the Otsu clot
      was not significantly different from normal when a tPA and plasminogen mixture
      was overlaid onto the clots. For Otsu, the penetration of the tPA/plasminogen
      mixture into the clot was much faster than normal and the protection against
      plasmin cleavage was impaired; however, tPA-induced plasmin activation of the
      Otsu fibrin was slower than that of normal fibrin, resulting in a clot lysis of
      Otsu similar to normal.

PMID- 16412497
TI  - Biochemistry examinations and health disorder evaluation of Taiwanese living near
      incinerators and with low serum PCDD/Fs levels.
AB  - The main objective of this study was to establish background levels of serum
      PCDD/Fs and biochemistry of residents living near municipal waste incinerators
      (MWIs) which had been operating between 1 and 8 years, and also to examine the
      association between the serum PCDD/Fs levels and health outcomes of interest.
      Information on medical history, life-style, and dietary habits was obtained by
      questionnaire interview. Significantly elevated levels of glucose and blood urea
      nitrogen (BUN) were found in those with low to high serum PCDD/Fs levels
      (p<0.05), and PCDD/Fs levels were found to be positively associated with glucose
      levels, and marginally with GGT levels even after adjusting for age, sex, BMI and
      smoking status. Although no conclusive findings on health disorder were
      associated with the accumulation of serum PCDD/Fs in our study participants, we
      suggest that the current biochemistry examinations only reflect partially the
      physiological change in glucose modulation and liver function. However, the low
      serum PCDD/Fs level does not seem to be sufficient in eliciting pathological
      process for diabetes or liver-related diseases. The findings suggest that the
      human body's biochemistry functions such as liver and glucose modulation were
      affected by PCDD/Fs exposure at even these low serum PCDD/Fs levels found in the
      general population. Other biochemical functions therefore should be further
      analyzed, especially for hormone-related and immune functions.

PMID- 16412499
TI  - Sequential prolonged oral topotecan and prolonged oral etoposide as second-line
      therapy in ovarian or peritoneal carcinoma: a phase I Gynecologic Oncology Group
      study.
AB  - OBJECTIVE: Preclinical models suggest synergy when topoisomerase I and II
      inhibitors are given sequentially, but not simultaneously. A phase I study was
      conducted in previously treated ovarian or peritoneal carcinoma to determine the
      tolerability (maximum number of days) of sequential oral topotecan and oral
      etoposide. METHODS: Topotecan (0.8 mg/m(2)) was administered daily (days 1-5)
      followed by etoposide (50 mg/m(2)) administered daily for up to 5 days (days 8
      12). Patients on dose levels 3 and 4 repeated topotecan for up to 5 days starting
      on day 15 after the initial topotecan and etoposide sequence. Cycles were
      repeated every 28 days. Dose-limiting toxicities (DLT) were defined as:
      neutrophils <1000/microl or platelets <50,000/microl before completing
      administration of etoposide or topotecan; neutropenic fever; platelets
      <20,000/microl; or a delay greater than 2 weeks in starting cycle 2 due to
      hematologic toxicity (ANC <1500/microl or platelets <100,000/microl on scheduled
      day of treatment). RESULTS: Nineteen patients were entered into this trial, and a
      total of 54 cycles (range 1-10) of therapy were administered. Dose-limiting
      toxicities, principally neutropenia, occurred when therapy was administered for 3
      of 4 weeks. CONCLUSION: Oral topotecan and oral etoposide administered at these
      doses daily for 5 days sequentially for a maximum of three (out of every four)
      weeks of therapy are tolerable. In some cases, it may be necessary to hold
      therapy the third week. Based on the activity seen in this patient population, it
      is planned to take this regimen into a phase II setting.

PMID- 16412500
TI  - Strain differences in the acquisition of nicotine-induced conditioned taste
      aversion.
AB  - Lewis (LEW) and Fischer (F344) rat strains differ on a variety of physiological
      and behavioral endpoints, including reactivity to drugs of abuse. Although they
      differ in drug reactivity, such assessments are generally limited to morphine and
      cocaine. To determine if these differences generalize to other drugs, the present
      study examined these strains for their reactivity to the affective properties of
      nicotine, specifically their sensitivity to nicotine in the conditioned taste
      aversion preparation. For four or five conditioning cycles given every other day,
      rats from both strains were allowed access to saccharin and injected with
      nicotine (0.1, 0.4, 0.8 mg/kg) or vehicle. On intervening days, all rats were
      given access to water and injected with vehicle. Under this one-bottle training
      and testing procedure, neither strain displayed aversions at the lowest dose of
      nicotine (0.1 mg/kg). Aversions were evident for both strains at 0.4 and 0.8
      mg/kg, although the F344 rats acquired the aversions at 0.4 mg/kg faster and
      displayed a significantly greater aversion at 0.8 mg/kg than subjects from the
      LEW strain. For both strains, aversions were evident at all doses (and in a dose
      dependent manner) when subjects were given access to saccharin and water in a two
      bottle test. There were, however, no strain differences on this test. Differences
      between the two strains in their acquisition of nicotine-induced taste aversions
      were discussed in the context of aversion assessments with other compounds as
      well as in relation to differences in the self-administration of nicotine in the
      two strains.

PMID- 16412501
TI  - Big brown dog or brown big dog? An electrophysiological study of semantic
      constraints on prenominal adjective order.
AB  - Event-related brain potentials (ERPs) were recorded while participants read and
      made acceptability judgments about sentences containing three types of adjective
      sequences: (1) normal sequences--e.g., Jennifer rode a huge gray elephant; (2)
      reversed sequences that violate grammatical-semantic constraints on linear order-
      e.g., *Jennifer rode a gray huge elephant; and (3) contradictory sequences that
      violate lexical-semantic constraints on compositionality--e.g., *Jennifer rode a
      small huge elephant. Relative to the control condition, the second adjective
      elicited a reduced N400 and an enhanced P600 in both the reversal condition and
      the contradiction condition. We present several alternative accounts of these two
      effects, but favor an interpretation which treats them as reflecting semantic and
      syntactic aspects of a temporary reanalysis of the adjective order construction.
      Furthermore, relative to the control condition, the final noun elicited a robust
      N400 in the contradiction condition but not in the reversal condition. We suggest
      that this effect indexes the full registration of the lexical-semantic
      incompatibility of the two adjectives in the contradiction condition. Finally, we
      discuss how all of these findings fit into the broader context of recent ERP
      studies that have reported atypical N400s and robust P600s in response to certain
      types of semantic anomalies.

PMID- 16412502
TI  - The antecedents and consequences of autonomous self-regulation for college: a
      self-determination theory perspective on socialization.
AB  - Using self-determination theory, two studies investigated the relations among
      perceived need support from parents, their adolescents' autonomous self
      regulation for academics, and the adolescents' well-being. Study 1 indicated that
      perceived need support from parents independently predicted adolescents' well
      being, although when mothers' and fathers' data were examined separately, the
      relation was stronger for mothers than for fathers. In Study 2, autonomous self
      regulation for planning to attend college was a significant partial mediator of
      the relation of adolescents' perceived need support to well-being. Thus,
      perceived need support from parents does seem important for the development of
      adolescents' autonomous self-regulation and well-being.

PMID- 16412503
TI  - Influences of ammonia plasma treatment on modifying depth and degradation of
      poly(L-lactide) scaffolds.
AB  - Hydrophobicity of poly(L-lactide) scaffolds is a main drawback in obtaining a
      sufficient mass of seeded cells for satisfying the requirements of tissue
      engineering. Plasma treatment is a useful technique to enhance the hydrophilicity
      of the scaffolds. However, the effect of this technique on the modifying depth
      and degradation of the scaffolds should be considered. In this paper, the
      influence of NH3 plasma treatment on the modifying depth and degradation of
      scaffolds were investigated. The results showed that the modifying depth of the
      scaffolds increased with treating time and the plasma power ranging from 20 to 80
      W influenced the depth slightly. However, the degradation of the scaffolds
      increased with increasing treatment time and plasma power. The results also
      showed that the plasma intruded the scaffolds gradually from top to bottom. For a
      4 mm thick scaffold, the optimized treatment condition was 20 W of power in a 30
      Pa ammonia atmosphere for 30 min of treating time. Under this condition, the
      integrity of scaffold could be relatively well kept. NH3 plasma treatment enabled
      the penetration of cells into scaffolds and facilitated the proliferation of
      cells in them.

PMID- 16412504
TI  - The influence of membrane lipid structure on plasma membrane Ca2+ -ATPase
      activity.
AB  - Lipid composition and Ca(2+)-ATPase activity both change with age and disease in
      many tissues. We explored relationships between lipid composition/structure and
      plasma membrane Ca(2+)-ATPase (PMCA) activity. PMCA was purified from human
      erythrocytes and was reconstituted into liposomes prepared from human ocular lens
      membrane lipids and synthetic lipids. Lens lipids were used in this study as a
      model for naturally ordered lipids, but the influence of lens lipids on PMCA
      function is especially relevant to the lens since calcium homeostasis is vital to
      lens clarity. Compared to fiber cell lipids, epithelial lipids exhibited an
      ordered to disordered phase transition temperature that was 12 degrees C lower.
      Reconstitution of PMCA into lipids was essential for maximal activity. PMCA
      activity was two to three times higher when the surrounding phosphatidylcholine
      molecules contained acyl chains that were ordered (stiff) compared to disordered
      (fluid) acyl chains. In a completely ordered lipid hydrocarbon chain environment,
      PMCA associates more strongly with the acidic lipid phosphatidylserine in
      comparison to phosphatidylcholine. PMCA associates much more strongly with
      phosphatidylcholine containing disordered hydrocarbon chains than ordered
      hydrocarbon chains. PMCA activity is influenced by membrane lipid composition and
      structure. The naturally high degree of lipid order in plasma membranes such as
      those found in the human lens may serve to support PMCA activity. The absence of
      PMCA activity in the cortical region of human lenses is apparently not due to a
      different lipid environment. Changes in lipid composition such as those observed
      with age or disease could potentially influence PMCA function.

PMID- 16412505
TI  - Parental experience of child protection intervention: a qualitative study.
AB  - OBJECTIVE: To explore the ways in which parents experience and negotiate child
      protection intervention. METHOD: A qualitative grounded theory approach was used.
      In-depth qualitative interviews explored the experiences of 18 parents who had
      received child protection services. Grounded theory methods were used to build a
      model representing the ways these parents perceived and reacted to intervention.
      RESULTS: The ways parents perceive workers using power was shown to be the
      primary influence shaping parents' views of intervention and their reactions to
      it. Two perceptions of power emerged: parents perceived power being used over
      them as a form of control or power with them as a form of support. Three ways of
      responding to intervention emerged: parents fought workers by openly opposing
      them, "played the game" by feigning co-operation, or worked with them in
      collaborative relationships. Parents experiencing power being used over them
      tended to fight or play the game while parents experiencing power being used with
      them tended to work with intervention. No evidence was found linking case type
      (non-voluntary or voluntary cases) to whether parents perceived power being used
      by workers over them or with them. CONCLUSIONS: Findings highlight the importance
      of practitioners and policy makers being aware of the impact power has on worker
      parent interaction. Doubts are raised about the viability of policies separating
      policing and helping in child protection through differential response systems.

PMID- 16412506
TI  - Prevalence of childhood sexual abuse among incarcerated males in county jail.
AB  - OBJECTIVE: The current study examined the prevalence and characteristics of
      childhood sexual abuse in a jailed-based population. METHODOLOGY: A
      retrospective, self-reported survey was administered over an 8-week period to a
      random sample of 100 men who were incarcerated in a county jail in Southeastern
      Texas. The survey included questions about childhood sexual experiences before
      and after puberty, drug history and use, and sexual risk-taking behaviors.
      RESULTS: Of the 100 male inmates who participated in this study, 59% reported
      experiencing some form of sexual abuse before puberty, and all such instances
      occurred before or at the age of 13 years. The first episode of childhood sexual
      abuse began at an average age of 9.6 years (SD = 2.4), and ended at an average
      age of 13.0 years (SD = 2.3). Kissing and touching without intercourse (64%) was
      the common pattern of sexual abuse experience reported. The total number of
      perpetrators was 165, with 10% male and 90% female. Friends (n = 72) and family
      (n = 56) were the most frequent perpetrators. CONCLUSION: Childhood sexual abuse
      may be more prevalent among inmates than among males in the general population.
      These results show a high percentage of inmates who report a history of childhood
      sexual abuse; this rate is higher than those reported by other studies for
      incarcerated males. The findings support the belief held by professionals in the
      criminal justice field that a significant number of incarcerated males may have
      been victims of sexual abuse.

PMID- 16412507
TI  - Identification and characterization of a myeloid differentiation factor 88
      (MyD88) cDNA and gene in Japanese flounder, Paralichthys olivaceus.
AB  - The interleukin-1 receptor/toll-like receptor (IL-1R/TLR) superfamily signaling
      involves myeloid differentiation factor 88 (MyD88) that acts as an important
      adapter protein. A Japanese flounder (Paralichthys olivaceus) MyD88 (jfMyD88)
      cDNA and gene were cloned, and found to have lengths of 1.5 and 3.01 kb,
      respectively. The ORF encodes 285 amino acids that contain a death domain and a
      Toll/IL-1 receptor domain. The gene is composed of 5 exons and 4 introns. The
      jfMyD88 gene is highly expressed in organs involved in immune functions,
      including the gills, intestines, kidney, skin and spleen. Three days after a fish
      was infected with Edwardsiella tarda, staining with anti-jfMyD88 polyclonal
      antibody revealed an increased population of MyD88-positive cells in the kidney
      and spleen. These results imply that MyD88 has an important role in the innate
      immune system in Japanese flounder.

PMID- 16412508
TI  - Outpatient commitment and coercion in New Zealand: a matched comparison study.
AB  - BACKGROUND: It has been hypothesized that a degree of coercion is a necessary
      component in using outpatient commitment to attain therapeutic outcome for those
      people subject to mental health law. However, what degree of coercion is required
      and how it is sustained is poorly understood. There is speculation that patients'
      recognition of beneficial as well as unwanted aspects of outpatient commitment
      (ambivalence) maybe an indicator that the necessary level of coercion has been
      achieved to facilitate a therapeutic outcome. AIM: The aim of this study was to
      determine the level of coercion perceived by those under outpatient commitment in
      New Zealand. Emphasis was given to consideration of the presence of ambivalence
      and the role of interactive processes, including procedural justice, in
      influencing patients' perceptions of coercion. METHOD: A cross-sectional
      comparative study was undertaken to compare the perceptions of coercion of
      patients on outpatient commitment (n = 69) to a matched sample of voluntary
      outpatients (n = 69), using the Perceived Coercion Scale. The influence of a
      range of variables, including patients' knowledge of and beliefs concerning
      outpatient commitment, were considered. RESULTS: Although the level of coercion
      for involuntary outpatients was relatively low, it was significantly higher than
      that experienced by voluntary outpatients. Yet involuntary outpatients were more
      likely to espouse benefits of outpatient commitment. Although there was an
      inverse correlation between perceptions of procedural justice and perceived
      coercion, procedural justice did not feature in the linear regression analysis.
      DISCUSSION: In the New Zealand context, involuntary outpatients hold contrasting
      views to outpatient commitment. We suggest that this ambivalence is an indicator
      that the degree of coercion is suffice to achieve therapeutic outcome.
      Furthermore, this study suggests the impact of procedural justice on patients'
      perceptions of coercion may be more crucial during admission to hospital than in
      the context of on-going community care.

PMID- 16412509
TI  - Different role for mouse and human CD3delta/epsilon heterodimer in preT cell
      receptor (preTCR) function: human CD3delta/epsilon heterodimer restores the
      defective preTCR function in CD3gamma- and CD3gammadelta-deficient mice.
AB  - The majority of T cell receptor (TCR) complexes in mice and humans consist of a
      heterodimer of polymorphic TCRalpha and beta chains along with invariant
      CD3gamma, delta, epsilon, and zeta chains. CD3 chains are present as
      CD3gammaepsilon, deltaepsilon, and zetazeta dimers in the receptor complex and
      play critical roles in the antigen receptor assembly, transport to the cell
      surface, and the receptor-mediated signal transduction. That CD3 chains play
      critical roles in thymocyte development is apparent from the analyses of CD3
      deficient mice. PreT cell receptor (preTCR)-mediated CD4(-)CD8(-) (double
      negative or DN) to CD4(+)CD8(+) (double positive or DP) transition is severely
      impaired in mice deficient in either CD3gamma, or epsilon, or zeta chain. In
      contrast, CD3delta deficiency impairs thymocyte maturation at the CD4(+)CD8(+)
      double positive (DP) stage suggesting that CD3delta is not required for the
      preTCR-mediated DN to DP transition. However, recent data suggest that a defect
      in human CD3delta results in impaired development at the DN stage indicating a
      role for hCD3delta in preTCR-mediated DN to DP transition. To determine if human
      CD3delta/epsilon (hCD3delta/epsilon) could mediate preTCR-mediated DN to DP
      transition, we employed a human CD3 transgene that encodes full length CD3delta
      and a truncated but functional form of CD3epsilon. Surprisingly, the transgene
      restored the defective preTCR function in not only CD3epsilon- but CD3gamma- and
      CD3gammadelta-deficient mice as well. A possible role for human CD3delta/epsilon
      heterodimer in the preTCR-mediated DN to DP transition is discussed.

PMID- 16412511
TI  - Preparation and in vitro photodynamic activity of novel silicon(IV)
      phthalocyanines conjugated to serum albumins.
AB  - The interactions of four novel silicon(IV) phthalocyanines (SiPc), namely
      SiPc[OC(3)H(5)(NMe(2))(2)](2) (1), SiPc[OC(3)H(5)(NMe(2))(2)](OMe) (2),
      {SiPc[OC(3)H(5)(NMe(3))(2)](2)}I(4) (3), and
      {SiPc[OC(3)H(5)(NMe(3))(2)](OMe)}I(2) (4) with human serum albumin (HSA), bovine
      serum albumin (BSA), and maleylated bovine serum albumin (mBSA) were studied by
      fluorescence spectroscopy. The fluorescence emission of the serum albumins was
      effectively quenched by these phthalocyanines mainly through a static quenching
      mechanism. The higher Stern-Volmer quenching constants for the unsymmetrically
      substituted phthalocyanines 2 and 4 suggested that they have a stronger
      interaction with these proteins than the symmetrically substituted analogues 1
      and 3. A series of non-covalent BSA or mBSA conjugates of these phthalocyanines
      were also prepared and evaluated for their in vitro photodynamic activity against
      HepG2 human hepatocarcinoma cells. The bioconjugation could enhance the
      photocytotoxicity of 1 and 4 by up to eight folds, but the effects on 2 and 3
      were negligible. The results could be partly explained by two counter-balancing
      effects, namely the enhanced uptake and increased aggregation tendency of
      phthalocyanine due to BSA conjugation. As shown by absorption spectroscopy, the
      tetracationic phthalocyanine 3 was significantly aggregated in the protein cavity
      and its photocytotoxicity remained the lowest among the four photosensitizers.

PMID- 16412512
TI  - New paramagnetic supramolecular adducts for MRI applications based on non
      covalent interactions between Gd(III)-complexes and beta- or gamma-cyclodextrin
      units anchored to chitosan.
AB  - Gd(III) complexes are used as magnetic resonance imaging (MRI) contrast agents
      because they greatly enhance the relaxation rate of water protons of tissues in
      which they distribute, an effect that is much more marked if the paramagnetic
      complex is part of a macromolecular system. Furthermore applications in molecular
      imaging, require that as many units of contrast agent as possible be directed to
      the site of interest. To this end we synthesised a polymer made of chitosan
      functionalized with beta- and gamma-cyclodextrins (CDs) that is able to form high
      affinity adducts with suitably functionalized Gd(III) complexes. beta- and gamma
      CDs were first treated with maleic anhydride to afford 6-monosubstituted
      derivatives that reacted regioselectively with the amino groups of chitosan.
      Reaction times and yields were markedly improved by carrying out these reactions
      under high-intensity ultrasound or microwave irradiation. Compared to the CD
      monomers, beta- and gamma-CD-chitosan adducts show large increases both in terms
      of their binding affinity towards Gd(III) complexes and in relaxivity values and
      they appear promising carriers for the in vivo vehiculation of Gd(III) complexes.

PMID- 16412510
TI  - Biased dA/dT somatic hypermutation as regulated by the heavy chain intronic iEmu
      enhancer and 3'Ealpha enhancers in human lymphoblastoid B cells.
AB  - Somatic hypermutation (SHM) in immunoglobulin gene (Ig) variable (V) regions is
      critical for the maturation of the antibody response. It is dependent on the
      expression of activation-induced cytidine deaminase (AID) and translesion DNA
      polymerases in germinal center B cells as well as Ig V transcription, as
      regulated by the Ig heavy chain (H) intronic enhancer (iEmu) and the 3' enhancer
      (3'Ealpha) region. We analyzed the role of these cis elements in SHM by stably
      transfecting Ramos human lymphoblastoid B cells with a rearranged human IgH chain
      VD (diversity) J (joining) DNA construct containing a V(H) promoter at the 5' end
      and C(H)1 and C(H)2 exons of Cgamma1 at the 3' end. In this construct, mutations
      preferentially targeted dA/dT basepairs in the RGYW/WRCY hotspot. Most of the
      dA/dT mutations and accompanying dC/dG mutations were transitions. Deletion of
      iEmu resulted in decreased SHM which could be partially restored by insertion of
      the IgH hs1,2 enhancer. Other two 3'Ealpha enhancers, hs3-hs4, did not
      significantly increase the mutation frequency, but further strengthened the dA/dT
      bias. The frequency and spectrum of the mutations were independent of the genomic
      integration of the transgene or V gene transcription level. Thus, we have
      established a novel in vitro system to analyze SHM and identify the role of
      multiple cis-regulatory elements in regulating dA/dT biased SHM. This model
      system will be useful to further address the role of other cis-regulating
      elements and recruited trans-acting factors in expressing the modalities of SHM.

PMID- 16412513
TI  - Synthesis, characterization, X-ray structure and DNA photocleavage by cis
      dichloro bis(diimine) Co(III) complexes.
AB  - Complexes of the type [Co(LL)2Cl2]Cl, where LL = N,N'-ethylenediamine (en), 2,2'
      bipyridine (bpy), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione
      (phendione) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been synthesized and
      characterized by elemental analyses, IR, UV-visible and NMR spectroscopy. Crystal
      structure of [Co(phendione)2Cl2]Cl x 0.5 HCl x 3.5 H2O has been solved and
      refined to R = 0.0552. The crystal is monoclinic with space group C2/c; a =
      25.730(2) A, b = 12.375(1) A, c = 18.979(2) A, beta = 119.925(1) degrees and Z =
      8. The DNA binding characteristics of the complexes, investigated by covalent
      binding assay, viscosity measurements and competitive binding fluorescence
      measurements show that the complexes interact with DNA covalently except the
      complex containing the planar dppz ligand which intercalates within the base
      pairs of DNA. The complexes containing en, phen and phendione cleave plasmid pBR
      322 DNA upon irradiation under aerobic conditions while the complex containing
      the dppz ligand cleaves DNA upon irradiation under inert atmosphere. Molecular
      modeling studies show that the minimized structure of [Co(phendione)2Cl2]+,
      maintained the octahedral structure while binding to the N7 of guanines and the
      ligand fits into the major groove without disrupting the helical structure of the
      B-DNA.

PMID- 16412515
TI  - Bacterial nitrate reductases: Molecular and biological aspects of nitrate
      reduction.
AB  - Nitrogen is a vital component in living organisms as it participates in the
      making of essential biomolecules such as proteins, nucleic acids, etc. In the
      biosphere, nitrogen cycles between the oxidation states +V and -III producing
      many species that constitute the biogeochemical cycle of nitrogen. All reductive
      branches of this cycle involve the conversion of nitrate to nitrite, which is
      catalyzed by the enzyme nitrate reductase. The characterization of nitrate
      reductases from prokaryotic organisms has allowed us to gain considerable
      information on the molecular basis of nitrate reduction. Prokaryotic nitrate
      reductases are mononuclear Mo-containing enzymes sub-grouped as respiratory
      nitrate reductases, periplasmic nitrate reductases and assimilatory nitrate
      reductases. We review here the biological and molecular properties of these three
      enzymes along with their gene organization and expression, which are necessary to
      understand the biological processes involved in nitrate reduction.

PMID- 16412514
TI  - Dps-like protein from the hyperthermophilic archaeon Pyrococcus furiosus.
AB  - Oxidative stress is a universal phenomenon experienced by organisms in all
      domains of life. Proteins like those in the ferritin-like di-iron carboxylate
      superfamily have evolved to manage this stress. Here we describe the cloning,
      isolation, and characterization of a Dps-like protein from the hyperthermophilic
      archaeon Pyrococcus furiosus (PfDps-like). Phylogenetic analysis, primary
      structure alignments and higher order structural predictions all suggest that the
      P. furiosus protein is related to proteins within the broad superfamily of
      ferritin-like di-iron carboxylate proteins. The recombinant PfDps protein self
      assembles into a 12 subunit quaternary structure with an outer shell diameter of
      approximately 10nm and an interior diameter of approximately 5 nm. Dps proteins
      functionally manage the toxicity of oxidative stress by sequestering
      intracellular ferrous iron and using it to reduce H(2)O(2) in a two electron
      process to form water. The iron is converted to a benign form as Fe(III) within
      the protein cage. This Dps-mediated reduction of hydrogen peroxide, coupled with
      the protein's capacity to sequester iron, contributes to its service as a
      multifunctional antioxidant.

PMID- 16412516
TI  - Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Respiratory viruses are a common trigger for exacerbations of chronic
      obstructive pulmonary disease (COPD). Human metapneumovirus (hMPV) is a
      paramyxovirus associated with respiratory tract infections and wheezing. Our aim
      was to determine whether hMPV was associated with exacerbations of COPD. METHODS:
      The study was designed as an observational cohort study carried out in a 944-bed
      urban teaching hospital located in New Haven, Connecticut. Between December 2002
      and May 2003, patients hospitalized due to an exacerbation of COPD were
      identified. Nasopharyngeal specimens obtained from these patients were tested for
      human metapneumovirus by RT-PCR and for respiratory syncytial virus, influenza A
      and B, parainfluenza-1, -2, and -3 and adenovirus by a cytospin-enhanced direct
      immunofluorescence assay and/or viral culture. RESULTS: Fifty individuals met
      enrollment criteria and hMPV was identified in 6 (12%), respiratory syncytial
      virus in 4 (8%), influenza A in 2 (4%) and parainfluenza type 3 in 1 (2%)
      patients. Both A and B hMPV genotypes were identified in patients hospitalized
      due to exacerbations of COPD. CONCLUSION: hMPV was frequently identified in
      patients hospitalized due to an exacerbation of COPD. Further studies are
      necessary to determine the epidemiology and the impact of hMPV in COPD patients.

PMID- 16412517
TI  - Neuregulins: versatile growth and differentiation factors in nervous system
      development and human disease.
AB  - The neuregulins are a family of growth and differentiation factors with a wide
      range of functions in the nervous system. The power and diversity of the
      neuregulin signaling system comes in part from a large number of alternatively
      spliced forms of the NRG1 gene that can produce both soluble and membrane-bound
      forms. The soluble forms of neuregulin are unique from other factors in that they
      have a structurally distinct heparin-binding domain that targets and potentiates
      its actions. In addition, a finely tuned, bidirectional mechanism regulates when
      and where neuregulin is released from neurons in response to neurotrophic factors
      produced by both neuronal targets and supporting glial cells. Together, this
      produces a balanced intercellular signaling system that can be localized to
      distinct regions for both normal development and maintenance of the mature
      nervous system. Recent evidence suggests that neuregulin signaling plays
      important roles in many neurological disorders including multiple sclerosis,
      traumatic brain and spinal cord injury, peripheral neuropathy, and schizophrenia.
      Here, we review the basic biology of neuregulins and relate this to research
      suggesting their involvement with and potential therapeutic uses for neurological
      disorders.

PMID- 16412518
TI  - The ABCs of computerized naming: equivalency, reliability, and predictive
      validity of a computerized rapid automatized naming (RAN) task.
AB  - Population-based studies indicate dual routes to disabled reading in adolescence
      and adulthood: slowed acquisition of single word reading and ADHD (particularly
      inattention) in early childhood. Impairments in rapid serial naming may be a
      factor common to both problems. The gold-standard measure of this ability, the
      Rapid Automatized Naming Task (RAN; [Denckla MB, Rudel R. Rapid automatized
      naming of pictured objects, colors, letters and numbers by normal children.
      Cortex 1974;10:186-202]), has traditionally been administered in a paper-pencil
      format. Recently however, researchers [Neuhaus GF, Carlson CD, Jeng WM, Post Y,
      Swank PR. The reliability and validity of rapid automatized scoring software
      ratings for the determination of pause and articulation component durations. Educ
      Psychol Meas 2001;61:490-504] have begun to use computerized versions of the RAN.
      Here a slightly modified computerized version of the RAN was created and the
      equivalency between the computerized RAN and the conventional version was
      investigated using a university student sample. Naming times on the conventional
      and computerized RAN were highly correlated, overall, and for each of the four
      RAN stimulus types (letters, digit, colors, objects). Conventional and
      computerized RAN times predicted reading rate and reading comprehension scores
      equally well and both showed very high test-retest reliability. With our
      university student sample, findings indicate equivalency between the two testing
      mediums in all areas examined.

PMID- 16412519
TI  - Health-related quality of life following ECT in a large community sample.
AB  - BACKGROUND: While electroconvulsive therapy (ECT) is a potent antidepressant,
      little is known about its long-term effects on health-related quality of life
      (HRQOL). METHODS: Using a naturalistic, observational design, 283 depressed
      patients, who received ECT at 7 hospitals in the New York City area, were
      assessed for HRQOL with the Medical Outcomes Study Short Form - 36 (SF-36) at
      baseline, several days after ECT, and 24 weeks later. Depression severity was
      assessed with the Hamilton Rating Scale for Depression, and a neuropsychological
      battery was also administered. RESULTS: Baseline SF-36 scores were very low,
      indicating poor HRQOL. These scores were improved at postECT and at the 24-week
      follow-up. Unexpectedly, the degree of retrograde amnesia for autobiographical
      information was associated with better HRQOL in the immediate postECT period, but
      not at 24-week follow-up. In contrast, improvement in global cognitive status was
      associated with superior HRQOL at the 24-week time point. LIMITATIONS: This study
      was limited by the lack of a non-ECT comparison group, and the naturalistic
      design of treatment. CONCLUSIONS: ECT is associated with improved HRQOL in the
      short- and long-term, with the enhancements largely explained by improvements in
      depressive symptoms. The acute cognitive effects of ECT may also influence HRQOL
      assessment, and evaluations removed in time from the treatment may have greater
      validity.

PMID- 16412520
TI  - Sensitivity to reward and punishment and the prefrontal cortex in major
      depression.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) show neuropsychological
      impairments, including deficient executive functions and altered sensitivity to
      reward and punishment. METHODS: Executive functions (Wisconsin Card Sorting Test,
      WCST) and contingency learning based on the cumulative effect of reward and
      punishment (Iowa Gambling Test, IGT) were assessed in 30 medicated patients with
      unipolar MDD and in 20 healthy control volunteers. In the classic ABCD version of
      the IGT, advantageous decks are characterized by immediate small reward but even
      smaller future punishment. In the modified EFGH version, advantageous decks are
      characterized by immediate large punishment but even larger future reward.
      RESULTS: Patients with MDD were impaired in the WCST and in the ABCD version of
      the IGT but showed normal performances on the EFGH task. Depression, but not
      executive dysfunctions, significantly predicted performances on the EFGH task:
      less severe depressive symptoms were associated with better performances on the
      EFGH task. LIMITATIONS: The sample size was small and only few neuropsychological
      tests were used. Unmedicated patients were not assessed. Individual personality
      style, response strategies, and behavioral impulsivity were not investigated.
      CONCLUSIONS: Medicated patients with MDD show altered sensitivity to reward and
      punishment: immediate large reward enhanced related response patterns even when
      the strategy was disadvantageous and immediate large punishment did not prohibit
      related response patterns. Impairments in emotional decision-making were not a
      pure consequence of executive dysfunctions.

PMID- 16412521
TI  - Time patterns of attempted suicide.
AB  - BACKGROUND: The association of mental disorders with time patterns of attempted
      suicide is poorly understood. METHODS: The study material consisted of all
      consecutive suicide attempts admitted to health care in Helsinki during a one
      year period from 15 January 1997 to 14 January 1998. Clinical diagnosis was made
      according to ICD-10. RESULTS: Overall, the rate of suicide attempts varied
      markedly during the study period, peaking in autumn and being lowest during
      winter. Substance use disorders best explained suicide attempts occurring at
      weekends. There was considerable temporal variation among patients with mood
      disorders, compared to only slight variation among patients with schizophrenia
      spectrum disorders. Study subjects tended to contact health services in the late
      evening and around midnight. Those contacting health services outside normal
      hours received psychiatric consultation less frequently than others and were
      referred to aftercare less often. LIMITATIONS: Structured Clinical Interviews for
      DSM-IV Axis I and II Disorders were not used. CONCLUSIONS: There were marked time
      patterns of attempted suicide, especially among patients with mood disorders and
      substance use disorders. This contrasted with the limited fluctuation among
      patients with schizophrenia spectrum disorders. Contacts with the health care
      system occurred most often in the late evening and around midnight. The findings
      question the adequacy of staff numbers for psychiatric consultations and of time
      to plan aftercare.

PMID- 16412522
TI  - Platelet 5-HT2A receptor binding and tryptophan availability in depression are
      not associated with recent history of suicide attempts but with personality
      traits characteristic for suicidal behavior.
AB  - BACKGROUND: Abnormalities in the serotonergic (5-HT) system have been implicated
      in the pathogenesis of suicidal behavior. Studies on peripheral serotonergic
      parameters as a measure for central serotonergic function in suicidal patients
      appear to be promising, yet failed to show a clear association with suicidality.
      The objective of this study was to elucidate the role of serotonergic blood
      parameters in depressed suicidal patients and to examine their usefulness as a
      potential biological marker for suicidality. A number of personality traits were
      assessed in order to provide a basis for a psychobiological model of suicidal
      behavior. METHODS: Depressed patients with a recent suicide attempt (SA; n = 59)
      were compared to those without history of suicide attempts (NSA; n = 28). 5-HT2A
      receptor binding in platelets and tryptophan/amino acid ratio in plasma were
      measured. Acute psychopathology and personality traits as well as characteristics
      of suicide attempts were assessed. RESULTS: There was no significant difference
      between SA and NSA in terms of peripheral serotonergic parameters as well as
      personality traits. However, the whole sample showed associations between certain
      personality traits and serotonergic platelet parameters. Furthermore, we observed
      a relation between suicidal ideation, lethality of suicide attempts and
      peripheral serotonergic markers. LIMITATIONS: The number of cases with data on
      peripheral markers is relatively low. The potential influence of antidepressant
      medication previous to study inclusion has to be taken into account. The study
      focussed on depressed patients only. CONCLUSIONS: Low serotonergic function is
      involved in the pathogenesis of suicidality, whereas the use of platelet 5-HT2A
      receptor activity and tryptophan availability as biological markers for
      suicidality in depressed patients could not be proven an appropriate tool.
      Alterations in the serotonergic system are associated with trait aggression and
      other character dimensions.

PMID- 16412523
TI  - The role of the endoplasmic reticulum Ca2+ store in the plasticity of central
      neurons.
AB  - The smooth endoplasmic reticulum (SER) is a well-characterized buffer and source
      of Ca2+ in both axonal and dendritic compartments of neurons. Ca2+ release from
      the SER can be evoked by stimulation of the ryanodine receptor or the inositol
      (1,4,5)-trisphosphate [Ins(1,4,5)P3] receptor. Both receptors can couple to the
      activation of neurotransmitter-gated receptors and voltage-gated Ca2+ channels on
      the plasma membrane, thus enabling the SER to discriminate between different
      types of neuronal activity. In axonal terminals, Ca2+-induced Ca2+ release (CICR)
      mediates spontaneous, evoked and facilitated neurotransmission. Store release
      might also regulate the mobilization and recycling of synaptic vesicles. In the
      dendritic compartment, the distribution of Ins(1,4,5)P3 receptors and ryanodine
      receptors influences the intracellular encoding of neuronal activity. Thus, the
      functionality of the Ca2+ store can affect both the polarity and the spatial
      extent of Ca2+-dependent shifts in synaptic efficacy. In hippocampal neurons, for
      example, CICR in the spine heads underlies homosynaptic plasticity, whereas
      heterosynaptic plasticity is mediated by Ins(1,4,5)P3-dependent Ca2+ signalling.
      Purkinje neurons primarily express Ins(1,4,5)P3 receptors in the spine heads, and
      long-term depression of synaptic efficacy is crucially dependent on Ins(1,4,5)P3.

PMID- 16412524
TI  - Molecular basis of Toxoplasma gondii atovaquone resistance modeled in
      Saccharomyces cerevisiae.

PMID- 16412525
TI  - Assessing risk factors of coronary heart disease and its risk prediction among
      Korean adults: the 2001 Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND: An in-depth assessment of coronary heart disease (CHD) risk factors
      in Koreans was conducted to develop effective risk reduction strategies for this
      population. METHOD: Based on 2001 Korea National Health and Examination Survey, a
      cross-sectional survey, this paper presents the prevalence of major CHD risk
      factors and estimates future risk by applying the Framingham model and CHD risk
      factor guidelines of the National Cholesterol Education Program Adult Treatment
      Panel III (NCEP) to 4639 Koreans aged 20 to 79 years. RESULT: Our findings
      indicate that CHD is a major health threat to Koreans. Among these factors, low
      high-density lipoprotein cholesterol (HDL-C) was seen in 35.1% of men and 17.8%
      of women; both had a low rate of controlled high blood pressure (men 13.7%, women
      23.6%), and age-adjusted current smoking was especially high (61.6%) in men. The
      10-year CHD risk averaged 11.1% in men and 5.5% in women based on Framingham
      model, and 7.4% and 1.4% based on NCEP guidelines. About 9.1% of men and 2.6% of
      women were "high-risk," (>20%) based on the Framingham model, and 4.7% and 0.7%,
      respectively, on the NCEP guideline. Diabetes was the most prevalent risk factor
      among high-risk individuals and total cholesterol in men and low HDL-C in women
      was fairly high regardless of prediction method. CONCLUSION: These findings
      suggest that current coronary heart health of Koreans is nearly comparable to
      that of western developed countries. Developing and implementing effective
      population-based intervention strategies focusing on diabetes is warranted to
      lower the CHD risk for Koreans.

PMID- 16412526
TI  - Quantification of phagocytosis of Aspergillus conidia by macrophages using a
      novel antibody-independent assay.
AB  - The pathogenic mould Aspergillus fumigatus can cause severe infections in
      immunocompromised patients. Phagocytosis of inhaled conidia is an early and
      crucial event in the defense of A. fumigatus infections. Here we describe a novel
      antibody-independent assay for quantification of phagocytosis, that in this study
      has been applied to different Aspergillus species, but that is in principle
      suitable for many fungi.

PMID- 16412527
TI  - Simultaneous separation of acid and basic bioactive peptides by electrodialysis
      with ultrafiltration membrane.
AB  - beta-Lactoglobulin (beta-lg), one of the major whey components, can release by
      enzymatic hydrolysis different bioactive peptidic sequences according to the
      enzyme used. However, these protein hydrolysates have to be fractionated to
      obtain peptides in a more purified form. The aim of the present work was to
      evaluate the feasibility of separating peptides from a beta-lg hydrolysate using
      an ultrafiltration (UF) membrane stacked in an electrodialysis (ED) cell and to
      study the effect of pH on the migration of basic/cationic and acid/anionic
      peptides in the ED configuration. Electrodialysis with ultrafiltration membrane
      (EDUF) appeared to be a selective method of separation since amongst a total of
      40 peptides in the raw hydrolysate, only 13 were recovered in the separated
      adjacent solutions (KCl 1 and KCl 2). Amongst these 13 migrating peptides, 3
      acid/anionic peptides migrated only in one compartment (KCl 1), while 3
      basic/cationic peptides migrated only in the second compartment (KCl 2) and that
      whatever the pH conditions of the hydrolysate solution. Furthermore, the highest
      migration was obtained for the ACE-inhibitory peptide beta-lg 142-148, with a
      value of 10.75%. The integrity of the UF membrane was kept and EDUF would
      minimize the fouling of UF membrane.

PMID- 16412529
TI  - Pre-operative plasma erythropoietin concentration and survival following surgery
      for non-small cell lung cancer.
AB  - BACKGROUND: Suppression of the effect of the hormone erythropoietin (EPO) on the
      bone marrow, and an inadequate EPO response to anaemia have been shown to be
      factors in the genesis of cancer related anaemia. Low haemoglobin (Hb)
      concentration pre-operatively has been shown to have prognostic significance in
      patients with surgically resected NSCLC. This study investigates the relationship
      between pre-operative EPO and survival in patients having surgery for NSCLC.
      METHODS: Pre-operative plasma EPO concentration and haemoglobin concentration
      were analysed in patients undergoing surgery for NSCLC between April 1998 and
      January 1999. Full follow-up was available for all patients. RESULTS: Forty two
      patients were included. Median EPO concentration was 9.4 mIU/ml, range (3.7-56.4)
      with 17 patients (40.4%) having values above the normal range. Median haemoglobin
      concentration was 13.3g/dl (range 8.5-16.8) with 15 patients (26%) anaemic pre
      operatively. Pathological staging revealed 17 (40.4%) patients with stage I, 6
      (14.3%) with stage II, 19 (45.3%) with stage III disease. Ten patients had
      irresectable disease. There was a significant difference in median EPO but not
      haemoglobin concentration, between the different pathological stages. Survival
      was significantly lower in patients with pre-operative EPO >10.5 mIU.
      CONCLUSIONS: Raised pre-operative EPO is associated with reduced survival in
      patients having surgery for NSCLC. Its measurement should be considered in the
      pre-operative assessment of patients undergoing surgery for NSCLC. Further
      research is required to further investigate the biological relationship between
      EPO and NSCLC.

PMID- 16412528
TI  - Social rates of return to investment in skills assessment and residency training
      of international medical graduates in Alberta.
AB  - Governments and physician organizations in Canada have identified current and
      anticipated future shortages of physicians. The creation of opportunities for
      licensure for the sizeable population of unlicensed international medical
      graduates (IMG) residing in Canada can alleviate some of the shortage of medical
      manpower. We examine whether expenditures on IMG skills assessment, training and
      licensing are a socially desirable use of resources. We estimate the financial
      rate of return to Alberta taxpayers from resources allocated to the Alberta
      International Medical Graduate (AIMG) program, started in 2001. Our estimates
      show that resources allocated to providing skills assessment and residency
      training opportunities for IMGs that lead to licensing as a Canadian physician
      generate real annual rates of return of 9-13%.

PMID- 16412530
TI  - Integration of multi-channel piezometry and electrical tomography to better
      define chemical heterogeneity in a landfill leachate plume within a sand aquifer.
AB  - The Hanai-Bruggeman effective medium theory is used to relate bulk electrical
      conductivity, measured by surface and cross-borehole images, to fluid electrical
      conductivity, surface conductance, porosity and the geometry factor, in a medium-
      to fine-grained sand deposit. The change in bulk EC is caused by the presence of
      a landfill leachate plume. Repeated electrical images over a period of 16 months
      indicate that various segments of the plume are moving. The chemical constituents
      of the leachate plume have been determined by sampling from a bundled piezometer
      located in the electrical image field. Very close agreement is demonstrated
      between the fluid EC anomaly and the presence of elevated bulk EC indicating that
      the electrical images can be used to map the plume geometry and to monitor the
      movement of the plume segments.

PMID- 16412531
TI  - Effect of some carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons
      on gap junction intercellular communication in hepatoma cell cultures.
AB  - One of the systems that regulate tissue homeostasis is gap junction intercellular
      communication (GJIC). It is accepted that the down-regulation of GJIC is linked
      to the tumor-promoting properties of carcinogens. In this study, the effect of
      some carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons (PAH) on
      GJIC was investigated. It was found that in hepatoma cell culture (Hep G2)
      carcinogenic PAH inhibited GJIC after 24 h exposure by 75-100% depending on the
      PAH structure. The inhibition effect on GJIC is reversible because removing the
      PAH by changing of culture medium restores the GJIC. The non-carcinogenic PAH do
      not significantly influence GJIC. alpha-Naphthoflavone, an inhibitor of PAH
      metabolism, has no effect on inhibition of GJIC by carcinogenic PAH. 2,3,7,8
      Tetrachloro-p-dibenzodioxin, an aryl hydrocarbon (Ah) receptor ligand, inhibits
      GJIC by about 50% only after 48 h exposure. To clarify the role of formation of
      PAH metabolites and interaction with Ah receptor on inhibition of GJIC, we
      determined the effect of benzo/a/pyrene on hepatoma G27 cells in which neither
      mRNA of CYP1A1 nor Ah receptor was determined. As in Hep G2 cells,
      benzo/a/pyrene, unlike non-carcinogenic benzo/e/pyrene, inhibits GJIC. We
      conclude that in the studied hepatoma cells carcinogenic PAH inhibit GJIC
      directly (that is, not via their metabolites) and this effect is not associated
      with Ah receptor interaction.

PMID- 16412532
TI  - Oxidative stress is not required for the induction of apoptosis upon glutamine
      starvation of Sp2/0-Ag14 hybridoma cells.
AB  - L-glutamine (Gln) withdrawal rapidly triggers apoptosis in the murine hybridoma
      cell line Sp2/0-Ag14 (Sp2/0). In this report, we examined the possibility that
      Gln deprivation of Sp2/0 cells triggers an oxidative stress which would
      contribute to the activation of apoptotic pathways. Gln withdrawal triggered an
      oxidative stress in Sp2/0 cells, as indicated by an increased accumulation of
      reactive oxygen species (ROS) and an increase in the intracellular content in
      protein carbonyl groups. Gln starvation also caused a decrease in the
      intracellular levels of glutathione (GSH). However, a decrease in GSH was not
      sufficient to induce Sp2/0 cell death since reducing GSH levels with DL
      buthionine-[S,R]-sulfoximine did not affect cell viability. The antioxidant N
      acetyl-L-cysteine (NAC), while effective in inhibiting ROS accumulation and
      oxidative stress, did not prevent the loss in cell viability or the processing
      and activation of caspase-3 triggered by Gln starvation. On the other hand, NAC
      did reduce the formation of apoptotic bodies in dying cells. Altogether these
      results indicate that in Sp2/0 cells, Gln deprivation leads to the induction of
      an oxidative stress which, while involved in the formation of apoptotic bodies,
      is not essential to the activation of the cell death program.

PMID- 16412533
TI  - Intermedin/adrenomedullin-2 dilates the rat pulmonary vascular bed: dependence on
      CGRP receptors and nitric oxide release.
AB  - Intermedin/adrenomedullin-2 (IMD/AM2) is a 47 amino acid peptide formed by
      enzymatic degradation of preprointermedin. The present study was undertaken to
      investigate the effects of rat IMD (rIMD) in the isolated buffer perfused rat
      lung (IBPR) under resting conditions and under conditions of elevated pulmonary
      vasoconstrictor tone (PVT). Under resting conditions in the IBPR, rIMD had little
      or no activity. When PVT was actively increased by infusion of U46619, bolus
      injection of IMD decreased pulmonary arterial pressure (PAP) in a dose-dependent
      manner. Since the pulmonary perfusion rate and left atrial pressure were
      constant, these reductions in PAP directly reflect reductions in pulmonary
      vascular resistance (PVR). The pulmonary vasodilator response to rIMD, when
      compared to calcitonin gene-related peptide (CGRP) on a molar basis, was greater
      at the lowest and midrange doses. The degree of inhibition by CGRP8-37 on
      pulmonary vasodilator response to rIMD was significantly less when compared to
      CGRP. Pretreatment with L-nitro-arginine-methyl ester (L-NAME), unlike
      meclofenamate and glybenclamide, significantly reduced the pulmonary vasodilator
      responses to rIMD. rIMD administration induced cross-tachyphylaxis to the
      pulmonary vasodilator response to CGRP whereas CGRP administration did not alter
      the ability of rIMD to dilate the IBPR. Pulmonary vasodilator responses to
      repeated injections of rIMD did not undergo tachyphylaxis. The present data
      demonstrate rIMD possesses direct vasodilator activity in the rat pulmonary
      vascular bed. The present data suggest activation of CGRP1 receptors and release
      of nitric oxide (NO*) mediate the pulmonary vasodilator response to rIMD whereas
      cyclooxygenase products and KATP channels do not contribute to the pulmonary
      vasodilator response to rIMD. The ability of rIMD to induce heterologous
      desensitization of CGRP1 receptor activation, to retain much of its pulmonary
      vasodilator activity after inhibition of CGRP1 receptors, and to lack homologous
      desensitization together suggests the pulmonary, unlike the systemic, vasodilator
      response to rIMD may depend on other vasodilator mechanisms including receptors
      in the calcitonin-receptor-like-receptor (CRLR) family.

PMID- 16412534
TI  - Melanocortin peptide therapeutics: historical milestones, clinical studies and
      commercialization.
AB  - The melanocortins (MCs) are a family of multifunctional peptidergic hormones.
      Several superpotent, prolonged acting, enzymatically resistant, MC analogs have
      been designed and synthesized to help clarify the nature and role of MCs and
      their receptors (MCRs) in physiological functions. Two of these analogs, a linear
      peptide, melanotan I, and a cyclic truncated peptide, melanotan II (MTI and MTII,
      respectively) have been patented and tested clinically for studies on tanning of
      the skin (MTI) and for diagnosis and treatment of male erectile dysfunction
      (MTII). A new MTII analog, PT-141 (Palatin Technologies) has initial phase I/II
      trials and is scheduled to enter pivotal stage III clinical trials leading to
      commercialization. MTI may provide a therapeutic tan with the potential to lower
      the risk of skin cancer. PT-141 may improve sexual functionality in both males
      and females.

PMID- 16412535
TI  - Pinealectomy causes hippocampal CA1 and CA3 cell loss: reversal by melatonin
      supplementation.
AB  - This experiment determined if the loss of endogenous melatonin via pinealectomy
      affected rat CA1 and CA3 pyramidal neuron numbers over a 20-month span. Since
      pinealectomy eliminates many neurohormones, some rats received daily melatonin
      supplementation to determine if this would reverse its effects. CA1 pyramidal
      cells were significantly reduced between 2 and 4 months after pinealectomy. CA3
      loss was evident at 2 months post-pinealectomy. Melatonin replacement in the
      drinking water prevented these effects and seemingly promoted the genesis of CA1
      cells. Analyses of hippocampal thiobarbituric acid reactive substances (TBARS)
      levels at 3 and 20 months post-surgery, revealed no significant group differences
      in lipid peroxidation. However, hippocampal TBARS were higher at 20 than at 3
      months in all groups. Pinealectomized rats exhibited a significantly higher ratio
      of reduced to oxidized glutathione at 3 months but not 20 months, when compared
      to the sham and melatonin-supplemented rats. This suggests that pinealectomy
      caused oxidative stress and a subsequent compensatory change in the glutathione
      system. These results indicate that endogenous melatonin is neuroprotective.

PMID- 16412536
TI  - Synthesis and in vitro cytotoxicity of 1,2,3,4-tetrahydroisoquinoline
      derivatives.
AB  - Several 1-alkyl-1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives, which may play
      a role in Parkinson's disease, have been synthesized via Pummerer-type
      cyclization of the sulfonium ion formed in situ from N-formyl sulfoxide. Using an
      in vitro trypan blue exclusion assay, high concentrations of TIQ derivatives
      possessing bulky alkyl group substituents such as 1-cyclobutyl-, 1-cyclohexyl-, 1
      phenyl- or 1-benzyl- at the C-1 position were found to significantly affect the
      viability of PC12 cells. Moreover, TIQ derivatives that moderately or strongly
      induced apoptosis (e.g., 1-phenyl-TIQ and 1-cyclohexyl-TIQ, respectively)
      paralleled the results obtained using the trypan blue exclusion assay. These
      results suggest that the size and electron-donating properties of functional
      groups may affect the cytotoxicity of TIQ derivatives.

PMID- 16412537
TI  - Registered nurses' and student nurses' assessment of pain and distress related to
      specific patient and nurse characteristics.
AB  - Previous studies examining the influence of patient and nurse characteristics on
      assessments of pain and distress are not consistent in their results. Few studies
      have focused on the influence of nurses' personality factors on the assessment of
      pain and distress. The aims of this study were to compare registered nurses' and
      student nurses' assessments of patients' pain and distress and to identify if the
      assessment relate to specific patient and nurse characteristics. Seventy-one
      registered nurses and 184 student nurses assessed pain and distress in three
      hypothetical cases and responded to personality factors scales. The assessments
      of pain and distress regarding the patients showed significant differences. The
      respondents were divided into two groups, respectively, for each patient
      according to whether the patient's experiences of pain and distress were assessed
      as more or less intense. Both the groups of registered nurses and student nurses
      showed significantly differences on personality factors. The groups of student
      nurses also differed on nursing experience. Patients' age, and type and stage of
      illness, personality factors, and nursing experience influenced the respondents'
      assessments. These findings can be used to help educators in nursing to develop
      strategies to improve skills and knowledge in the assessment at pain and
      distress.

PMID- 16412538
TI  - Assessment of acid leachable trace metals in sediment cores from River Uppanar,
      Cuddalore, Southeast coast of India.
AB  - An acid leachable technique is employed in core samples (C1, C2 and C3) to
      develop a baseline data on the sediment quality for trace metals of River
      Uppanar, Cuddalore, southeast coast of India. Acid leachable metals (Fe, Mn, Cr,
      Cu, Ni, Co, Pb, Zn and Cd) indicate peak values at the sulphidic phase and
      enrichment of metals in the surface layers are due to the anthropogenic
      activities. Association of trace metals with Fe, Mn indicates their adsorption
      onto Fe-Mn oxyhydroxides and their correlation with S indicate that they are
      precipitated as metal sulphides. Factor analysis identified three possible types
      of geochemical associations and the supremacy of trace metals along with Fe, Mn,
      S and mud supports their geochemical associations. Factor analysis also signifies
      that anthropogenic activities have affected both the estuarine and fresh water
      regions of River Uppanar.

PMID- 16412539
TI  - Nitrification in polluted soil fertilized with fast- and slow-releasing nitrogen:
      a case study at a refinery landfarming site.
AB  - The nitrifying activity and the effect of fertilization with urea and methylene
      urea were studied in a landfarming site. The site has been operative over 20
      years and maintained by heavy nitrogen fertilization. The landfarming soil
      contained 4-6% (w/w) oil. The nitrate accumulation was 20-50mg NO3-N day(-1)kg(
      1) observed after methylene urea fertilization of 889 g Nm(-2). Nitrification ex
      situ (in laboratory conditions) was 8.8 mg NO3-N day(-1) kg(-1) in the presence
      of 380 mg kg(-1) NH4+-N. The half-saturation concentration of nitrification was
      more than 200 mg NH4+-N kg(-1). The results show that nitrification was active in
      soil with high oil concentration. Urea fertilization of 893 g Nm(-2) caused an
      increase of soil NH4+-N concentration up to 5500 mg kg(-1) and pH>8.5. This led
      to inhibition of nitrification, which persisted after NH4+ concentration
      decreased below 200mg NH4+ kg(-1).

PMID- 16412540
TI  - Studies of mercury pollution in a lake due to a thermometer factory situated in a
      tourist resort: Kodaikkanal, India.
AB  - Kodaikkanal, India, suffered mercury contamination due to emissions and waste
      from a thermometer factory. Kodai Lake is situated to the north of the factory.
      The present study determined mercury in waters, sediment and fish samples and
      compared the values with those from two other lakes, Berijam and Kukkal. Total
      mercury (Hg(T)) of 356-465 ng l(-1), and 50 ng l(-1) of mercury in methyl mercury
      form were seen in Kodai waters while Berijam and Kukkal waters showed
      significantly lower values. Kodai sediment showed 276-350 mg/kg Hg(T) with about
      6% methyl mercury. Berijam and Kukkal sediments showed Hg(T) of 189-226 mg/kg and
      85-91 mg/kg and lower methylation at 3-4% and 2%, respectively. Hg(T) in fish
      from Kodai lake ranged from 120 to 290 mg/kg. The results show that pollution of
      the lake has taken place due to mercury emissions by the factory.

PMID- 16412541
TI  - Gender differences in alcohol and substance use relapse.
AB  - This review explores gender differences in relapse and characteristics of relapse
      events in alcohol and substance use. For alcohol, relapse rates were similar
      across gender. Although negative mood, childhood sexual abuse, alcohol-related
      self-efficacy, and poorer coping strategies predicted alcohol relapse, gender did
      not moderate these effects. Gender did moderate the association between marriage
      and alcohol relapse. For women, marriage and marital stress were risk factors for
      alcohol relapse; among men, marriage lowered relapse risk. This gender difference
      in the role of marriage in relapse may be a result of partner differences in
      problem drinking. Alcoholic women are more likely to be married to heavy drinking
      partners than are alcoholic men; thus, alcoholic women may be put at risk of
      relapse by marriage and alcoholic men may be protected by marriage. There are
      fewer studies documenting gender differences in substance abuse relapse so
      conclusions are limited and tentative. In contrast to the lack of gender
      differences in alcohol relapse rates, women appear less likely to experience
      relapse to substance use, relative to men. Women relapsing to substance use
      appear to be more sensitive to negative affect and interpersonal problems. Men,
      in contrast, may be more likely to have positive experiences prior to relapse.

PMID- 16412542
TI  - A systematic and conceptual review of posttraumatic stress in childhood cancer
      survivors and their parents.
AB  - Recent years have witnessed a rapid acceleration in the recognition and
      documentation of posttraumatic stress disorder (PTSD) and posttraumatic stress
      symptomatology (PTSS) in childhood cancer survivors and their parents. However,
      applicability of PTSD both diagnostically and conceptually to cancer-related
      traumatic responses remains poorly articulated within the current literature.
      Following an outline of childhood cancer and PTSD, this paper critically examines
      the applicability of such a diagnosis to this clinical population. It then
      systematically reviews the current evidence base (24 studies) on PTSD and PTSS in
      childhood cancer survivors and their parents. Prevalence of PTSD and PTSS, as
      well as associated predictors, in this clinical population varies widely.
      Findings are considered in the light of a number of contemporary theories of
      PTSD. Limitations within current conceptualizations of PTSD are highlighted with
      respect to the nature of cancer as a traumatic event and the specific features of
      traumatic stress manifestations in childhood cancer survivors and their parents.
      Finally, a number of pertinent research areas are elucidated which are argued to
      warrant further investigation.

PMID- 16412543
TI  - A rationale for determining, testing, and controlling specific impurities in
      pharmaceuticals that possess potential for genotoxicity.
AB  - The synthesis of pharmaceutical products frequently involves the use of reactive
      reagents and the formation of intermediates and by-products. Low levels of some
      of these may be present in the final drug substance and drug product as
      impurities. Such chemically reactive impurities may have at the same time the
      potential for unwanted toxicities including genotoxicity and carcinogenicity and
      hence can have an impact on product risk assessment. This paper outlines a
      procedure for testing, classification, qualification, toxicological risk
      assessment, and control of impurities possessing genotoxic potential in
      pharmaceutical products. Referencing accepted principles of cancer risk
      assessment, this document proposes a staged threshold of toxicological concern
      (TTC) approach for the intake of genotoxic impurities over various periods of
      exposure. This staged TTC is based on knowledge about tumorigenic potency of a
      wide range of genotoxic carcinogens and can be used for genotoxic compounds, for
      which cancer data are limited or not available. The delineated acceptable daily
      intake values of between approximately 1.5 microg/day for approximately lifetime
      intake and approximately 120 microg/day for < or = 1 month are virtually safe
      doses. Based on sound scientific reasoning, these virtually safe intake values do
      not pose an unacceptable risk to either human volunteers or patients at any stage
      of clinical development and marketing of a pharmaceutical product. The intake
      levels are estimated to give an excess cancer risk of 1 in 100,000 to 1 in a
      million over a lifetime, and are extremely conservative given the current
      lifetime cancer risk in the population of over 1 in 4
      (http://seer.cancer.gov/statfacts/html.all.html). The proposals in this document
      apply to all clinical routes of administration and to compounds at all stages of
      clinical development. It is important to note that certain types of products,
      such as those for life-threatening indications for which there are no safer
      alternatives, allow for special considerations using adaptations of the
      principles outlined in this paper.

PMID- 16412544
TI  - Healing traditions and men's sexual health in Mumbai, India: the realities of
      practiced medicine in urban poor communities.
AB  - Men's pre- and extra-marital sexual behavior has been identified as the primary
      factor in the growing HIV/STI epidemic among both males and females in India. One
      major barrier to reaching men has been their underutilization of public health
      services, which has severely limited programs geared to prevention and early case
      identification. A significant number of men in India have strong culturally-based
      sexual health concerns, much of which are derived from "semen-loss" and
      deficiencies in sexual performance. This paper reports on an ongoing Indo-US
      project that has focused on men's concerns about sexual health problems and
      assesses the services provided by non-allopaths in three low-income communities
      in Mumbai. Findings indicate that the primary health resources for these men are
      private, community-based non-allopaths, who identify themselves as ayurvedic,
      unani and homeopathic providers. The paper suggests that the combination of
      strong culturally-based sexual health concerns and the presence of private non
      allopaths who manage these problems present a window of opportunity for
      intervention programs to address the challenge of HIV/STI prevention and early
      case identification in India.

PMID- 16412545
TI  - Human leukocyte antigen DR1 in Japanese and Turkish patients with schizophrenia.
AB  - The main focus of this review has been to discuss the probable causes of the
      higher frequency of HLA DR1 antigen in patients with schizophrenia from Japan and
      Turkey, and also to see whether there was an impact of belonging to the Ural
      Altaic language group. A general medline search on the terms HLA and
      schizophrenia was used as the method to determine HLA studies in patients with
      schizophrenia. Most of the findings were inconsistent regarding the increased or
      decreased frequencies of different Class I and II antigens. However, there were
      interesting results, which have been consistently repeated in several Japanese
      studies and in a Turkish study. HLA DR1 antigen was statistically significantly
      increased in Japanese and Turkish patients with schizophrenia. As Japanese and
      Turkish languages belong to the Ural-Altaic language group, HLA DR1 antigen might
      have a specific association with schizophrenia in Japanese and Turkish patients.
      Searching the frequency of HLA DR1 antigen in patients with schizophrenia in
      other members of Ural-Altaic language group is necessary to support this
      hypothesis. Other language groups (e.g. Indo-European) should be assessed as
      well.

PMID- 16412546
TI  - Extrapyramidal side effects with atypical neuroleptics in bipolar disorder.
AB  - OBJECTIVE: To examine, in a real-world clinical setting, the risk of
      extrapyramidal symptoms (EPS) with atypical neuroleptics in bipolar patients.
      METHODS: The authors assessed 51 individual patient trials of atypical
      neuroleptic agents (17 risperidone, 13 olanzapine, 11 quetiapine, 8 ziprasidone,
      and 2 aripiprazole) in 37 bipolar patients (type I or type II). Risk of EPS was
      assessed using the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating
      Scale, and the Simpson-Angus Scale. Mean duration of treatment was 25.5 weeks
      (range 3-107 weeks) and 60.8% of patients were female. RESULTS: 62.7% of trials
      resulted in moderate to severe EPS. EPS and discontinuation frequencies were
      similar between specific neuroleptic agents or between high potency
      (risperidone/ziprasidone/aripiprazole; 52.9%, 27/51 trials) and low potency
      (quetiapine/olanzapine; 47.1%, 24/51 trials) agents. In a multiple regression
      model adjusted for confounders, akathisia was less common with low potency
      agents. Younger age was associated with more akathisia. 31.4% (11/35) of trials
      discontinued due to side effects. 7.8% (4/51) of trials led to mild de novo
      tardive dyskinesia. CONCLUSIONS: Over one-half of bipolar patients experienced
      EPS in this real world clinical setting. This rate is much higher than the 5-15%
      range reported in clinical trials, suggesting potential problems with clinical
      trial generalizability.

PMID- 16412547
TI  - Serotonin 1A and 2A receptor densities, neurochemical and behavioural
      characteristics in two closely related mice strains after long-term isolation.
AB  - Knowledge about individual differences in behavioural traits and their
      neurostructural and neurochemical correlates should improve therapeutic
      approaches of corresponding psychopathology. The presented investigations are
      aimed to reveal interrelationships between central nervous serotonergic [5-HT]
      receptor densities and neurochemical as well as behavioural traits in two mice
      strains. Male AB-Halle [ABH] and AB-Gatersleben [ABG] mice differing in
      aggression were investigated after 6 weeks of isolation housing. 5-HT1A and 5
      HT2A receptors were analysed in different brain regions by in vitro
      autoradiography. HPLC determinations of aminergic transmission in the cortex,
      hippocampus, striatum as well as in the raphe-region and radioimmunoassay
      determination of serum corticosterone were done before (basal condition) and
      after behavioural tests (challenge condition). Receptor autoradiography revealed
      higher 5-HT1A receptor densities, especially in limbic regions, and lower 5-HT2A
      receptor densities in the basal ganglia of ABH mice. Furthermore, ABH mice
      characterized as behaviourally more active in the open field and plus maze as
      well as more reactive and aggressive during the social interaction test showed
      lower basal 5-hydroxyindolacetic acid [5-HIAA] concentrations in the hippocampus,
      cortex and raphe-region as well as a different activation pattern in
      serotonergic, dopaminergic and noradrenergic brain systems after challenge in
      comparison to ABG mice. Additionally lower corticosterone concentrations were
      found in ABH mice. Lower basal serotonergic and striatal dopaminergic, but higher
      basal cortical dopaminergic metabolism in contrast to enhanced challenge-induced
      central nervous serotonergic and cortical dopaminergic reactivities are discussed
      to be crucial for an enhanced reactive behavioural trait, which could secondarily
      result in aggression-related behaviours, where higher 5-HT1A receptor and lower 5
      HT2A receptor densities may be essential.

PMID- 16412548
TI  - The descriptive epidemiology of obsessive-compulsive disorder.
AB  - Since the early eighties, there has been a growing interest in the descriptive
      epidemiology of obsessive-compulsive disorder (OCD). In this narrative review,
      the authors describe the findings of a number of studies that employed selected
      instruments, such as the Diagnostic Interview Schedule, the Composite
      International Diagnostic Instrument, and the Schedule for Affective Disorders and
      Schizophrenia, to ascertain the prevalence and incidence rates for OCD in several
      different countries. We noted that there is a great heterogeneity of findings and
      that the potential reasons for this variability include not only the intrinsic
      characteristics of the population under study but also extrinsic factors (i.e.,
      the several methodologically-informed decisions that are to be made before
      undertaking such investigations, such as the adoption of a specific diagnostic
      instrument). In order to further the knowledge on the epidemiology of OCD, it
      would be worthwhile to establish a global consensus regarding a standard
      assessment package for OCD, to produce more cross-culturally valid versions of
      the key research instruments, and to conduct studies specifically aimed at
      comparing the sociodemographic, clinical and prognostic aspects of OCD across
      different countries.

PMID- 16412549
TI  - Neonatal isolation alters estrous cycle effects on ventral striatal extracellular
      monoamine levels.
AB  - We demonstrated that neonatal isolation (ISO) enhances cocaine self
      administration in male and female adult rats and alters ventral striatal
      extracellular levels of serotonin (5-HT) and dopamine (DA) basally or in response
      to psychostimulants in infant rats. Now, we examine basal 5-HT, DA, and
      norepinephrine (NE) levels in nucleus accumbens (NAc) using in vivo microdialysis
      in adult male and female rats with or without ISO experience. NAc shows estrous
      cycle-dependent effects as do behavioral responses to cocaine. Because our prior
      work showed ISO eliminated estrous-cycle effects on behavior, we now test
      separate groups of females in proestrus, estrus, or diestrus stages. Litters were
      assigned to the ISO (1-h isolation; postnatal days 2-9) or non-handled (NH)
      condition. During adulthood (postnatal day 70-90), microdialysis probes were
      implanted and aimed at NAc core. Ten samples were collected over 150-min and
      measures of 5-HT, DA, and NE were analyzed via HPLC. ISO did not affect 5-HT
      levels in males. However, ISO modified estrous stage effects on 5-HT. The pattern
      of 5-HT levels in NH females (higher in diestrus and proestrus vs. estrus) was
      reversed in ISO females. DA levels were unaffected by ISO, similar to our
      findings at other ages, and did not differ by gender or estrous stage. None of
      these factors affected NE levels. Because 5-HT modulates DA and levels of both
      transmitters are increased by cocaine, this neurochemical effect of ISO may
      contribute to the ability of ISO to alter the behavioral responses to cocaine as
      we showed previously.

PMID- 16412550
TI  - Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in
      rats.
AB  - Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome
      were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats
      by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10
      and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and
      last chronic tianeptine injections and saline were done 30 min before ethanol
      withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were
      observed for 5 min, and withdrawal signs which included locomotor hyperactivity,
      agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures
      were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats)
      was also tested after acute tianeptine treatments. Acute but not chronic
      tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol
      dependent rats. Both acute and chronic tianeptine treatment produced some
      significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors
      and audiogenic seizures during the ethanol withdrawal. Our results suggest that
      acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in
      ethanol-dependent rats and this drug may be useful for treatment of ethanol-type
      dependence.

PMID- 16412551
TI  - Haemodynamic response to acute hypovolaemia, rapid blood volume expansion and
      adrenaline administration in an infant animal model.
AB  - We performed a prospective experimental animal study in seven sedated and
      mechanically ventilated piglets weighing 9+/-0.8 kg, to assess the haemodynamic
      response to acute hypovolaemia, rapid blood volume expansion and adrenaline
      (epinephrine) administration in an infant animal model. Withdrawal of 20 mL/kg of
      blood (hypovolaemia), rapid infusion of 20 mL/kg of blood (expansion) and the
      administration of 0.01 mg/kg of adrenaline were made in each animal. Heart rate,
      mean blood pressure (MBP), central venous pressure (CVP), pulmonary capillary
      pressure (PCP), cardiac index (CI), systemic vascular resistance index (SVRI),
      left ventricular contractility (Dp/dtmax), blood volume variables, including
      intrathoracic blood volume index (ITBI), global end-diastolic volume (GEDVI) and
      extravascular lung water index (ELWI). Hypovolaemia produced a significant
      decrease in the pressure, volume and CI variables, with an increase in SVRI and a
      decrease in Dp/dtmax. After expansion, all variables returned towards normal,
      with persistence of the SVRI increase and Dp/dtmax decrease. Changes in the blood
      volume variables (ITBI and GEDVI) were larger than in the pressure variables
      (CVP, PCP) in the case of both hypovolaemia and expansion. Adrenaline caused a
      slight increase in heart rate, MBP, CVP, PCP and Dp/dtmax with a greater increase
      in SVRI. None of the interventions led to changes in ELWI. We conclude that acute
      hypovolaemia produces an increase in SVRI and a decrease in Dp/dtmax that does
      not return fully to normal with restoration of blood volume. ITBI and GEDVI are
      more sensitive to changes in blood volume than CVP and PCP. Rapid blood volume
      expansion and adrenaline administration do not affect extravascular lung water.

PMID- 16412552
TI  - A randomised placebo-controlled trial of prolonged prednisolone administration to
      patients with HELLP syndrome remote from term.
AB  - OBJECTIVES: To evaluate the effect of prolonged administration of high-dose
      prednisolone on early onset HELLP (hemolysis, elevated liver enzymes, and low
      platelets) syndrome during expectant management. STUDY DESIGN: A randomized,
      double-blind trial was performed in 31 pregnant women with HELLP syndrome with an
      onset before 30 weeks gestation. Patients received either 50mg prednisolone or
      placebo intravenously twice a day. Primary outcome measures were the entry-to
      delivery interval and the number of recurrent HELLP exacerbations in the
      antepartum period. RESULTS: Serious maternal morbidity was considerable, in
      particular in the placebo group where even on maternal occurred as a consequence
      of liver rupture. The mean entry-delivery interval did not differ between the
      prednisolone group (6.9 days) and the placebo group (8.0 days). However, patients
      in the prednisolone group had a significant lower risk of a recurrent HELLP
      exacerbation after the initial crisis had subsided, as compared to patients in
      the placebo group (HR 0.3, with 95% CI 0.3-0.9). Platelet count recovered faster
      in the prednisolone group as compared to the placebo group (mean 1.7 days versus
      6.2 days, P<0.01). CONCLUSIONS: HELLP syndrome remote from term causes high risk
      for serious maternal morbidity and mortality. When expectant management is
      pursued in selected patients with a HELLP syndrome remote from term, prolonged
      administration of prednisolone reduces the risk of recurrent HELLP syndrome
      exacerbations.

PMID- 16412553
TI  - Coexistence of a round ligament dermoid cyst and struma ovarii in pregnancy.

PMID- 16412554
TI  - Horner's syndrome: an ominous sign in breast cancer.

PMID- 16412555
TI  - Genome-wide profiling of segmental-regulated transcriptomes in human epididymis
      using oligo microarray.
AB  - Sperm maturation during passage through the epididymis depends on regionalized
      gene expression which maintains the progressively changing environment within the
      epididymal tubule. Towards defining the genes that drive the sequential
      maturation of spermatozoa, we profiled regionally regulated gene expression
      pattern in the epididymis of a fertile young male donor using Affymetrix human
      genome U133 plus 2.0 microarray representing approximately the whole human
      genome. Over 15000 transcripts, almost one-third of the total on the array were
      identified in whole epididymis. Among them, 65% were detected in all three
      regions of the epididymis, 410 or 2.6% were present only in one region and the
      remaining 32.4% were distributed in two regions. Region-specific transcripts
      observed in caput (264), corpus (61) and cauda (81) epididymides were further
      classified as empirically determined reported genes or ESTs. This study revealed
      for the first time, the expression in human epididymis of a number of region
      specific genes. The original data will be made publicly available on the Shanghai
      Science and Technology Database
      (http://www.scbit.org/human_epididymis_transcriptomes).

PMID- 16412556
TI  - Active site analysis of 17beta-hydroxysteroid dehydrogenase type 1 enzyme
      complexes with SPROUT.
AB  - Estrogens, especially estradiol, have been shown to stimulate the proliferation
      of hormone-dependent types of breast cancer cells. 17Beta-hydroxysteroid
      dehydrogenase type 1 (17beta-HSD1) enzyme catalyses the synthesis of the active
      female estrogen, estradiol and is thus an attractive target for structure-based
      ligand design for the prevention and control of breast tumour growth. In this
      study, the active site of 17beta-HSD1 has been reviewed, and three crystal
      structure complexes (estradiol/NADP+, equilin/NADP+, dehydroepiandrosterone) of
      17beta-HSD1 have been selected to be analysed for de novo ligand design. The
      boundary surface, hydrophobic interactions and hydrogen bonding sites in the
      ligand binding domain for each ligand complex were analysed to create a
      comprehensive image of the active site.

PMID- 16412557
TI  - Oxidative stress, sperm survival and fertility control.
AB  - The human spermatozoon is highly susceptible to oxidative stress. This process
      induces peroxidative damage in the sperm plasma membrane and DNA fragmentation in
      both the nuclear and mitochondrial genomes. Such stress may arise from a variety
      of sources including a lack of antioxidant protection, the presence of redox
      cycling xenobiotics, infiltrating leukocytes and excess reactive oxygen species
      production by the spermatozoa. Whenever the levels of oxidative stress in the
      male germ line are high, the peroxidation of unsaturated fatty acids in the sperm
      plasma membrane ensures that normal fertilization cannot occur. However, at lower
      levels of oxidative stress, spermatozoa may retain their capacity for
      fertilization while carrying significant levels of oxidative damage in their DNA.
      Epidemiological evidence suggests that subsequent aberrant repair of such damage
      in the zygote may result in the creation of mutations associated with pre-term
      pregnancy loss and a variety of pathologies in the offspring, including childhood
      cancer. Thus, while the induction of oxidative stress in spermatozoa is causally
      involved in the aetiology of male infertility, the prospects of using such a
      strategy for male contraception is fraught with potential problems, should the
      suppression of fertility be incomplete and DNA-damaged spermatozoa gain access to
      the oocyte.

PMID- 16412558
TI  - Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic
      reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1.
AB  - 11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is essential for the
      local activation of glucocorticoid receptors (GR). Unlike unliganded cytoplasmic
      GR, 11beta-HSD1 is an endoplasmic reticulum (ER)-membrane protein with lumenal
      orientation. Cortisone might gain direct access to 11beta-HSD1 by free diffusion
      across membranes, indirectly via intracellular binding proteins or,
      alternatively, by insertion into membranes. Membranous cortisol, formed by 11beta
      HSD1 at the ER-lumenal side, might then activate cytoplasmic GR or bind to ER
      lumenal secretory proteins. Compartmentalization of 11beta-HSD1 is important for
      its regulation by hexose-6-phosphate dehydrogenase (H6PDH), which regenerates
      cofactor NADPH in the ER lumen and stimulates oxoreductase activity. ER-lumenal
      orientation of 11beta-HSD1 is also essential for the metabolism of the
      alternative substrate 7-ketocholesterol (7KC), a major cholesterol oxidation
      product found in atherosclerotic plaques and taken up from processed cholesterol
      rich food. An 11beta-HSD1 mutant adopting cytoplasmic orientation efficiently
      catalyzed the oxoreduction of cortisone but not 7KC, indicating access to
      cortisone from both sides of the ER-membrane but to 7KC only from the lumenal
      side. These aspects may be relevant for understanding the physiological role of
      11beta-HSD1 and for developing therapeutic interventions to control
      glucocorticoid reactivation.

PMID- 16412559
TI  - Mutagenesis as an unbiased approach to identify novel contraceptive targets.
AB  - To accommodate diverse personal needs in family planning, diverse contraceptive
      approaches are desirable. This goal requires identification of new contraceptive
      targets. Phenotype-driven mutagenesis is an unbiased approach to identify novel
      genes and functions in reproductive processes. The ReproGenomics Program at The
      Jackson Laboratory is a United States National Institutes of Health resource for
      production, identification and distribution of mutant mouse models of infertility
      that can be used for identification of potential targets for contraception. The
      strategy of this program is whole genome, random ENU mutagenesis, coupled with a
      phenotype screen for breeding failure as the only phenotype. A three-generation
      breeding scheme selects recessive mutations affecting reproductive functions. G3
      males and females that fail to reproduce by natural mating to wild-type animals
      undergo secondary phenotype screens to assess gonad and accessory organ
      histology, hormone production, gamete production and gamete function in
      fertilization. The genetic transmission of the infertility trait in each family
      is confirmed and each mutation is genetically mapped to a defined chromosome
      region, facilitating identification of candidate genes from sequence and
      expression databases. Genes essential for fertility in both males and females and
      acting both meiotically and post-meiotically have been identified by this
      strategy. Phenotypes include male infertility with normal sperm count, but
      failure in fertilization of oocytes. Phenotype descriptions of each mutation are
      posted on the program website, . These unique reproductive mutant mouse resources
      will lead to new discoveries in andrology (and gynecology) research, as well as
      reproductive medicine. Dissection of gene function in known and newly discovered
      reproductive pathways will expand our focus to reveal novel targets for
      contraception.

PMID- 16412560
TI  - Inhibition of transforming growth factor-beta/Smad signaling by
      phosphatidylinositol 3-kinase pathway.
AB  - Gastrin-releasing peptide (GRP) activates phosphatidylinositol 3-kinase (PI3
      K)/Akt, an important cell survival signaling pathway, to stimulate growth of
      various cell types. Transforming growth factor (TGF) superfamily ligands activate
      intracellular Smad signaling to regulate cell growth, differentiation and
      apoptosis; dysregulation of the TGF-beta/Smad pathway has been noted in cancer
      cells. Therefore, we sought to determine whether a potential cross-talk exists
      between the TGF-beta/Smad and PI3-K pathways in the regulation of neuroblastoma
      cell growth. Increased Smad DNA binding was noted in SK-N-SH human neuroblastoma
      cells when treated with LY294002, an inhibitor of PI3-K, by transcription
      factor/DNA array analysis and electrophoretic mobility shift assay. LY294002
      treatment resulted in Smad2 accumulation in the nuclei and an increased Smad
      binding element (SBE)-luciferase activity. These findings were corroborated by co
      transfection with pCGNN-Deltap85 plasmid, which expresses a PI3-K mutant p85
      subunit. In contrast, GRP treatment decreased Smad binding activity in
      neuroblastoma cells. Our findings demonstrate that the PI3-K pathway negatively
      regulates TGF-beta/Smad signaling in neuroblastoma cells. GRP-induced activation
      of PI3-K, resulting in neuroblastoma cell growth promotion, is potentiated by
      down-regulation of TGF-beta/Smad signaling.

PMID- 16412561
TI  - The clinical significance of twist expression in nasopharyngeal carcinoma.
AB  - The present study was aimed to determine twist expression in nasopharyngeal
      carcinoma (NPC) and to investigate the clinicopathological significance in the
      progress of NPC. Semiquantitative RT-PCR and Western blotting were carried out to
      investigate the expression of Twist in NPC cell lines and normal nasopharyngeal
      epithelial cell line, which showed that both Twist mRNA and protein were up
      regulated in the tumor cells in comparison with the normal cells. We then
      examined Twist mRNA expression in non-cancerous nasopharyngeal mucosa (10 cases)
      and NPC (95 cases) using in situ hybridization. The results showed that Twist was
      overexpressed in 59 of 95 (62.1%) NPC samples. In contrast, there was no obvious
      expression of Twist mRNA in non-cancerous tissues. In addition, another 75 NPC
      samples were analyzed by immunohistochemistry, and 33 of the 75 samples were
      shown to be positive for Twist protein. Both Twist mRNA expression and Twist
      protein expression were positively associated with lymph-node metastasis and
      distant metastasis. Furthermore, expression of Twist protein was correlated with
      the NPC prognosis. Patients with NPC who were Twist protein-positive had a worse
      5-year survival rate. These findings demonstrate that the Twist may play an
      important role in the invasion and metastasis of NPC. Twist protein is valuable
      marker for assessing the prognosis of NPC.

PMID- 16412562
TI  - Skin delivery potency and antitumor activities of temozolomide ester prodrugs.
AB  - Clinical trials have shown temozolomide to be an effective agent for treatment of
      malignant melanoma. In order to investigate its suitability for delivery via the
      skin, a series of temozolomide esters was synthesized as prodrugs. In vitro
      assays demonstrated temozolomide, temozolomide acid and the hexyl ester equi
      effective against selected cancer cell lines. The susceptibility of the esters to
      enzyme hydrolysis and their effectiveness for application to the skin were
      investigated. The esters effectively diffuse through rat skin and the hexyl ester
      demonstrated profound potency for penetrating through skin. Topical application
      of 5% (w/v) hexyl ester in DMSO solution on a mouse model demonstrated a
      significant inhibition of tumor growth. These results suggest that temozolomide
      esters could be an effective alternative to temozolomide in the treatment of skin
      cancer.

PMID- 16412563
TI  - Interleukin-12 is associated with the in vivo anti-tumor effect of mistletoe
      extracts in B16 mouse melanoma.
AB  - Viscum album (VA) preparations consist of aqueous extracts of different types of
      lectins of mistletoe. VA exert cytotoxic and immunomodulatory properties that may
      be relevant for the inhibition of tumor growth. We addressed the effects of VA
      preparation VA Qu FrF on growth of B16F1 melanoma implanted in mice and on
      proliferation and cytokine synthesis of splenocytes. In C57BL6 mice, inhibition
      of tumor growth by VA was associated with an enhancement of splenocyte
      proliferation and with an up-regulation of IL-12 secretion. In IL-12-deficient
      strain of mice the inhibition of melanoma growth by VA and the splenocyte
      proliferation were abrogated. Results from the present study strongly suggest a
      crucial role of IL-12 in the anti-tumor properties of VA extracts.

PMID- 16412564
TI  - Hybrid aza-steroid alkylators in the treatment of colon cancer.
AB  - We tested two alkylating homo-aza-steroid esters, lactandrate and lactestoxate,
      for antineoplastic activity against colon adenocarcinoma in vitro and in vivo.
      Cytostatic and cytotoxic activity was evaluated in vitro with the SRB colormetric
      assay against nine human colon adenocarcinoma cell lines. The in vivo anti-tumour
      effect was determined against two rodent colon carcinomas, the Colon 26 and the
      relatively chemoresistant Colon 38 carcinoma, as well as against the human
      xenograft CX-1 colon carcinoma. Both of the tested compounds displayed a very
      satisfactory anti-cancer activity in vitro and in vivo. Lactestoxate produced a
      significantly higher overall activity than lactandrate.

PMID- 16412565
TI  - Quantitative analysis of plasma circulating DNA at diagnosis and during follow-up
      of breast cancer patients.
AB  - The aim of the present project was to quantify the level of plasma DNA in
      patients with malignant or non-malignant breast diseases and in healthy controls,
      then investigate whether such measurements have diagnostic or prognostic value.
      Plasma DNA from 121 women (61 patients with breast cancer, 33 control patients
      with benign breast diseases and 27 healthy control individuals) was quantified by
      a real-time quantitative polymerase chain reaction (PCR) method. Plasma DNA
      concentration in the breast cancer patients (median 65 ng/ml) was significantly
      higher (P<0.05) than that in the control patients (median 22 ng/ml) or healthy
      control (median 13 ng/ml). No association was observed between plasma DNA levels
      and clinicopathological parameters. The data suggest that quantification of
      plasma circulating DNA may be a valuable complementary diagnostic tool in
      discriminate breast cancer from unaffected individuals and may be proposed as an
      early detection test as well as a new, noninvasive assay to follow-up patients.

PMID- 16412566
TI  - Functional polymorphism 57Val>Ile of aurora kinase A associated with increased
      risk of gastric cancer progression.
AB  - Overexpression or amplification of the aurora kinase A (AURKA) gene induces
      chromosomal instability and transformation. AURKA SNPs are associated with
      several human cancers but their association with gastric cancer has yet to be
      investigated. In this study, 501 gastric cancer patients and 427 controls were
      genotyped for two coding SNPs in AURKA, 91A>T (31Ile>Phe) and 169G>A (57Val>Ile).
      Allele or genotype association with gastric cancer susceptibility was not
      observed in comparisons between the patient and control samples. However, 169G/G
      genotype was significantly more frequent in advanced gastric cancers than in
      early gastric cancers (age/sex-adjusted OR=2.2, 95% CI=1.3-3.8, P=0.0042).
      Moreover, the elevated risk of gastric cancer progression was associated with 91T
      169G (age/sex-adjusted OR=1.9, 95% CI=1.1-3.4, P=0.025) and 91A-169G (age/sex
      adjusted OR=1.6, 95% CI=1.0-2.6, P=0.048) haplotypes, having approximately 2.5
      fold higher kinase activity than 91T-169A haplotype. The results suggest that
      169G>A in AURKA is associated with progression of gastric cancer by affecting
      relative kinase activities of AURKA variants.

PMID- 16412567
TI  - Inhibition of gastric cancer cells associated angiogenesis by 15d-prostaglandin
      J2 through the downregulation of angiopoietin-1.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been
      shown to inhibit angiogenesis. We showed that treatment with 15d-PGJ(2), a
      PPARgamma ligand, downregulate the expressions of angiopoietin-1 (Ang-1) in
      gastric cancer cells MKN45. The medium of MKN45 cells treated with 15d-PGJ(2)
      significantly inhibited the migration and tube formation of human umbilical vein
      endothelial cells (HUVECs). Moreover, Matrigel plug assay revealed that 15d
      PGJ(2) reduced in vivo angiogenesis induced by MKN45 cells. These modulations
      were restored by the addition of recombinant Ang-1. Our findings supported that
      15d-PGJ(2) suppressed angiogenesis of gastric cancer cells by downregulation of
      Ang-1.

PMID- 16412568
TI  - Pectic polysaccharide isolated from Angelica gigas Nakai inhibits melanoma cell
      metastasis and growth by directly preventing cell adhesion and activating host
      immune functions.
AB  - The pectic polysaccharide (angelan) of Angelica gigas Nakai is an
      immunostimulator that activates the immune functions of B cells and macrophages.
      Here we investigated the effect of angelan on tumor growth and metastasis.
      Angelan was found to significantly prolong the survival rate of B16F10-implanted
      mice and to reduce the frequency of pulmonary metastasis of B16F10 melanoma.
      Moreover, the combined treatment of angelan and doxorubicin (a cytotoxic
      anticancer agent) more effectively inhibited tumor growth and metastasis than
      either compound alone. In the present study, we found that angelan directly
      inhibited cancer cell adhesion and invasion through the extracellular matrix, in
      addition to activating the immune functions of B cells and macrophages. These
      results suggest that angelan can inhibit tumor growth and metastasis by
      stimulating host immunity and directly inhibiting cancer cell adhesion.

PMID- 16412569
TI  - mtDNA mutations in invasive cervix tumors: a retrospective analysis.
AB  - We tested whether mtDNA mutations are associated with poor outcome in patients
      with invasive cervix cancer. Tumor samples were banked more than 10 years ago
      from women with diagnoses of invasive cervix cancer. Automated techniques were
      used to determine the sequence of the mtDNA-encoded Complex I subunits.
      Approximately one-third of all tumors had multiple mtDNA sequence alterations.
      Both univariate and multivariate analysis of the 10 years survival probability
      showed that the 10 years survival of patients whose tumors had eight or more
      nucleotide substitutions was significantly worse (P<0.0063 and P<0.012,
      respectively). The log-rank test also found a significant difference in overall
      survival (P<0.003). These results suggest that multiple mtDNA mutations are an
      independent marker of poor prognosis, and that prospective clinical trials that
      incorporate analysis of mitochondrial genetic alterations in cervix cancer are
      warranted.

PMID- 16412570
TI  - Intracellular localization and concentration as well as photodynamic effects of
      benzoporphyrin derivative monoacid ring A in four types of rodent tumor cells.
AB  - The relative sensitivities of different tumor cells to photodynamic therapy (PDT)
      with benzoporphyrin derivative monoacid ring A (BPD-MA) were compared in the four
      tumor cells. A good correlation was observed between the cell survival at 0.1
      microg/ml of BPD-MA and sensitizer uptake/10(6) cells (r = -0.99) or the plating
      efficiency of cells (r = 0.99). At 3 h after the irradiation, a significant
      difference was observed in the proportion of apoptotic cells among the four tumor
      cells (p = 0.024). In conclusion, cell responses to PDT depend on the several
      factors such as the cell line, photosensitizer dose, and fluence.

PMID- 16412571
TI  - PTEN function in normal and neoplastic growth.
AB  - The PTEN tumor suppressor is a central negative regulator of the PI3K/AKT
      signaling cascade that influences multiple cellular functions including cell
      growth, survival, proliferation and migration in a context-dependent manner.
      Dysregulation of this signaling pathway contributes to many cancers in man. PTEN
      is the most commonly altered component of the PI3K pathway in human malignancies.
      Mutations occur in both heritable and sporadic settings, with high frequency in
      sporadic glioblastoma, prostate and endometrial cancer. Data from human tumors
      and animal models support the concept that the effects of PTEN inactivation are
      tissue-specific. Elucidation of the mechanisms regulating activation of unique
      downstream effectors that mediate distinct outcomes of PTEN loss will augment our
      understanding of tumorigenesis and ultimately lead to novel therapeutic options.

PMID- 16412572
TI  - Enhanced growth inhibition of squamous cell carcinoma of the head and neck by
      combination therapy of fusaric acid and paclitaxel or carboplatin.
AB  - Combination of a single dose of paclitaxel with three different dosages of FA
      resulted in significant (P<0.001) reductions in cell number from controls,
      paclitaxel alone, and FA treatments alone at four different time points.
      Combination of a single dose of carboplatin with three different dosages of FA
      resulted in significant (P<0.001) reductions in cell number from controls and
      carboplatin treatment alone at 72 and 96 h. Our data suggest that these
      combinations may provide an enhanced anti-tumor effect with respect to HNSCC.
      Since, FA can be administered orally, this regimen may introduce a paradigm
      change in chemotherapy for HNSCC.

PMID- 16412573
TI  - Effect of alpha1-adrenergic receptor antagonist on the noradrenaline-induced
      facilitation in respiratory rhythm in newborn rat pons-medulla-spinal cord
      preparations.
AB  - We hypothesized that facilitation of respiratory rhythm by noradrenaline (NA) in
      rat pons-medulla-spinal cord preparations is mediated through alpha1-adrenergic
      receptors. In 0- to 4-day-old rats, the respiratory frequency (fR) was monitored
      at the C4 ventral root and trigeminal motor (VMO) outputs. fR at temperature
      (Te)=23 degrees C was lower than that at a higher Te (27 degrees C) and was
      increased by NA. At 23 degrees C, lower concentrations of NA were needed to
      produce the same increases in fR seen at 27 degrees C. With highest NA
      concentration we tested (50 microM), activity at C4 was maintained in all
      preparations at both Te, whereas that at VMO was maintained in 50% (27 degrees C)
      or 88% (23 degrees C) of the preparations. Particularly, tonic activity at C4
      appeared in all preparations at both Te, but that at the VMO occurred in 0% (27
      degrees C) or 18% (23 degrees C) of the preparations. Based on these results, we
      used the lower Te (23 degrees C) and applied a low concentration of NA (3 microM)
      to the preparations. We found that: (1) with the addition of NA, fR was increased
      without the occurrence of tonic activity and (2) NA-related fR facilitation was
      inhibited by pre-treatment with the alpha1-adrenergic receptor antagonist
      prazosin (2 microM). fR was increased by application of the alpha1-adrenergic
      receptor agonist phenylephrine (4 microM), and this response was inhibited by
      prazosin (4 microM). At Te=23 degrees C, fR facilitation by NA in newborn rat
      pons-medulla-spinal cord preparations was obtained by activation of alpha1
      adrenergic receptors.

PMID- 16412574
TI  - A novel polymorphism in SEL1L confers susceptibility to Alzheimer's disease.
AB  - Alzheimer's disease (AD) is considered to be a conformational disease arising
      from the accumulation of misfolded and unfolded proteins in the endoplasmic
      reticulum (ER). SEL1L is a component of the ER stress degradation system, which
      serves to remove unfolded proteins by retrograde degradation using the ubiquitin
      proteosome system. In order to identify genetic variations possibly involved in
      the disease, we analysed the entire SEL1L gene sequence in Italian sporadic AD
      patients. Here we report on the identification of a new polymorphism within the
      SEL1L intron 3 (IVS3-88 A>G), which contains potential binding sites for
      transcription factors involved in ER-induced stress. Our statistical analysis
      shows a possible role of the novel polymorphism as independent susceptibility
      factor of Alzheimer's dementia.

PMID- 16412575
TI  - Amyloid-beta at sublethal level impairs BDNF-induced arc expression in cortical
      neurons.
AB  - Alzheimer's disease (AD) is characterized by progressive memory loss and
      cognitive dysfunction that probably due to a deficit in synaptic plasticity. One
      member of neurotrophins, brain-derived neurotrophic factor (BDNF), is known to be
      involved in the hippocampal long-term potentiation (LTP), a cellular model for
      learning and memory. Moreover, activity-regulated cytoskeleton-associated gene
      (Arc), an immediate early gene, is found to be a downstream effector of the BDNF
      signaling cascade. Inhibition of Arc protein synthesis impairs both the
      maintenance of LTP and the consolidation of long-term memory. In addition, the
      formation of senile plaques is a pathological feature in AD and mainly consists
      of the deposition of amyloid-beta (Abeta), a proteolytic product of amyloid
      precursor protein. Several studies concerning neurobehavioral performance have
      suggested that Abeta at sublethal levels interfere with the signaling cascades
      critical for synaptic plasticity and thus lead to the cognitive impairment in
      early stage of AD. Whether the BDNF-mediated Arc synthesis is impaired by
      sublethal Abeta in early AD is still unclear. Therefore, in the present study,
      primary cultures of neonatal rat cortical neurons were used to evaluate the
      effect of sublethal Abeta on the BDNF-induced Arc protein expression. Consistent
      with the literature, Arc, an indicator of synaptic plasticity, was induced by
      BDNF (25 ng/ml) in both dose- and time-dependent manners. After treating cultures
      with sublethal Abeta (5 microM), a significant suppression was observed on the
      level of BDNF-induced Arc protein expression. This result indicates that Abeta at
      sublethal level impairs the BDNF-mediated signaling in cortical neurons and thus
      underlies the deficits of synaptic plasticity occurred at the early stage of AD
      before significant neuronal loss.

PMID- 16412576
TI  - Early induction of calpains in rotenone-mediated neuronal apoptosis.
AB  - Rotenone is an inhibitor of mitochondrial complex I that produces a model of
      Parkinson's disease (PD), where neurons undergo apoptosis by caspase-dependent
      and/or caspase-independent pathways. Inhibition of calpains has recently been
      shown to attenuate neuronal apoptosis. This study aims to establish for the first
      time, the time-point of calpain activation with respect to the caspase activation
      and the possibility of cell cycle re-entry in rotenone-mediated cell death.
      Immunoblot results revealed calpain activation occurred at 5, 10h prior to
      caspase-3 activation (at 15 h), suggesting calpain activation was an earlier
      cellular event compared to caspase activation in the rotenone-mediated apoptosis.
      In addition, an upregulation of phospho-p53 was observed at 21 h. However, no
      expression or upregulation of cell cycle regulatory proteins including cdc25a,
      cyclin-D1 and cyclin-D3 were observed, strongly suggesting that cell cycle re
      entry did not occur. These findings provide new insights into the differential
      patterns of calpain and caspase activation that result from rotenone poisoning
      and which may be relevant to the therapeutic management of PD.

PMID- 16412577
TI  - Purification and biochemical characterization of a fibroblast growth factor
      binding protein (FGF-BP) from the lactoferrin fraction of bovine milk.
AB  - By means of gel filtration on a TSK-gel HPLC column in the presence of 8 M urea,
      a 37-kDa polypeptide (p37) was completely separated from lactoferrin (LF) in the
      heparin HII fraction of the partially purified LF fraction prepared from bovine
      milk. Purified p37 was identified as a fibroblast growth factor-binding protein
      (FGF-BP), since its N-terminal 14 amino acid residues (KKEGRNRRGSKASA) were 100%
      identical to the corresponding sequence of bovine FGF-BP. It was found, in vitro,
      that (i) p37 had a higher binding affinity with bFGF than bLF; (ii) p37
      functioned as a phosphate acceptor for at least three protein kinases (PKA, CK1
      and CK2); (iii) bLF stimulated about 3-fold the PKA-mediated phosphorylation of
      p37, but suppressed its phosphorylation by CK1; and (iv) galloyl pedunculagin was
      an effective inhibitor for the phosphorylation of p37 by PKA and CK1.
      Furthermore, the physiological correlation between p37 and bLF may be regulated
      through specific phosphorylation of p37 by PKA, since p37 fully phosphorylated by
      PKA did not bind to bLF in vitro. The sulfatide-induced conformational changes in
      p37 enabled the phosphorylation of p37 by CK1 and also reduced its ability to
      bind with bLF in vitro. From these results presented here, it is concluded that
      (i) p37 (FGF-BP) may be tightly associated with bLF in bovine milk; and (ii) the
      physiological correlation between p37 and bLF may be regulated by the PKA
      mediated full phosphorylation of p37 or by the direct binding of sulfatide to p37
      in vivo.

PMID- 16412578
TI  - Lysosomes and lysosomal proteins in cancer cell death (new players of an old
      struggle).
AB  - Death of cancer cells influences tumor development and progression, as well as
      the response to anticancer therapies. This can occur through different cell death
      programmes which have recently been shown to implicate components of the acidic
      organelles, lysosomes. The role of lysosomes and lysosomal enzymes, including
      cathepsins and some lipid hydrolases, in programmed cell death associated with
      apoptotic or autophagic phenotypes is presented, as evidenced from observations
      on cultured cells and living animals. The possible molecular mechanisms that
      underlie the action of lysosomes during cell death are also described. Finally,
      the contribution of lysosomal proteins and lysosomes to tumor initiation and
      progression is discussed. Elucidation of this role and the underlying mechanisms
      will shed a new light on these 'old' organelles and hopefully pave the way for
      the development of novel anticancer strategies.

PMID- 16412579
TI  - Psychometric evaluation of the smoking cessation Processes of Change scale in an
      adolescent sample.
AB  - The Processes of Change are the cognitions, behaviors, and emotions that people
      employ to change their behaviors. However, the processes of change remain the
      least studied dimension of the transtheoretical model. The present study presents
      a psychometric evaluation of the short form of the processes of change inventory
      for smoking cessation in an adolescent sample of 798 ninth-grade smokers from 22
      Rhode Island high schools. The majority of the sample was white (87.2%), split
      approximately evenly as regards to gender (48.1% female), with an average age of
      14.3 (SD=0.6) years of age. The same hierarchical model established on the adult
      sample was fit to the 20-item inventory. This model included 10 primary factors
      representing the processes of change and two second order factors that grouped
      the processes into five behavioral and five experiential processes of change.
      Model fit indices (RMSEA=0.08, CFI=0.92) supported the hypothesized structure.
      External validation was established by testing for stage differences in the use
      of the ten processes. A significant MANOVA (F(4,793)=18.517, p<0.001) and
      separate ANOVAs demonstrated that the use of all ten processes increased across
      the stages, as predicted by the transtheoretical model of behavior change. The
      processes of change help guide researchers, clinicians, and intervention program
      developers towards effective strategies to assist individuals at all stages of
      change progress towards healthier behaviors.

PMID- 16412580
TI  - Donation of surplus cryopreserved oocytes and ovarian tissue sections--should the
      medical institution involved in cryopreservation and storage possess exclusive
      rights of distribution to prospective recipients?

PMID- 16412581
TI  - Reduced tolerance of exercise in fibromyalgia may be a consequence of impaired
      microcirculation initiated by deficient action of nitric oxide.
AB  - Although the underlying mechanism responsible for muscular fatigue and exercise
      intolerance remains to be elucidated, it is reported two major mechanisms,
      central and peripheral hypothesis. As a peripheral mechanism, there are few
      reports on abnormalities of the microcirculation in patients with fibromyalgia.
      The key point to note is that ischemia associated with a modest decline in tissue
      oxygen causes muscle fatigue. It has been shown that have been found low muscle
      levels of phosphates and abnormalities in microcirculation in fibromyalgia. Based
      on several novel data, production abnormalities of nitric oxide level might lead
      to symptoms of fatigue as a long term effect. There a vicious cycle concerning
      impairment of microcirculation in FM. The cycle is firstly initiated decrease of
      production of nitric oxide in the endothelial level by some trigger factors.
      Changed level of nitric oxide may cause microcirculation abnormalities in the
      tissue levels, muscular region. At the end of these phases, muscular fatigue and
      exercise intolerance may progressively develop in the FM. It is possible that
      this theory appears to provide a physiopathological explanation for decreased
      exercise capacity in patients with fibromyalgia. This paper describes a plausible
      mechanism for the development of exercise intolerance on microcirculation
      abnormalities.

PMID- 16412582
TI  - Endometriosis associated with defective handling of apoptotic cells in the female
      genital tract is a major cause of autoimmune disease in women.
AB  - Several autoimmune diseases are far more common in women than men. The reasons
      are unknown. Recent studies have shown that many autoimmune diseases which
      predominantly affect females are characterized by the production of
      autoantibodies against components of apoptotic cells. Furthermore, in
      experimental animals, defective clearance of apoptotic cells in a pro-oxidant
      inflammatory environment can trigger the production of these autoantibodies and
      related autoimmune disease. Endometriosis is characterized by defective clearance
      of apoptotic endometrial cells in a pro-oxidant inflammatory environment. It is
      proposed that this combination of abnormalities triggers autoantibody production
      in women affected by endometriosis. A proportion of these women will be
      genetically predisposed to develop overt autoimmune disease. As endometriosis
      affects at least 4% of the female population of reproductive age, this phenomenon
      will have a major effect on the gender prevalence of several related autoimmune
      syndromes. The hypothesis is supported by epidemiological studies which show a
      strong association between endometriosis and female-predominant autoimmune
      disorders.

PMID- 16412583
TI  - Sunshine and suicide: bright light may lead to serotonin-driven behavioural
      activation without improvement in depressive cognitive deficits.

PMID- 16412585
TI  - Intertrial interval as a contextual stimulus.
AB  - Four experiments with rats investigated whether the time between appetitive
      conditioning trials can serve as a discriminative cue for responding during the
      next conditional stimulus (CS). In Experiment 1, rats that received extinction
      trials with a 4-min intertrial interval (ITI) showed spontaneous recovery after a
      retention interval of 16 min, whereas rats that received extinction with a 16-min
      ITI did not. Experiments 2 and 3 investigated more explicit discriminations
      between the 4- and 16-min ITIs. When a 16-min ITI signaled that the CS would be
      reinforced and a 4-min ITI signaled that it would not, the ITIs modulated
      responding to the CS. But when the 4-min ITI signaled reinforcement and the 16
      min ITI did not, there was less evidence of modulation by the ITIs. This
      asymmetry was due at least partly to a difficulty in performance rather than
      learning. Experiment 4 investigated similar discriminations with 1- and 4-min
      ITIs. Here the results took a different form: time in the reinforced ITI elicited
      responding directly, but did not modulate responding to the CS. ITI can function
      as a contextual cue, and the results suggest new similarities between the
      processes behind interval timing and associative learning.

PMID- 16412584
TI  - An adjunctive preventive treatment for heart disease and a set of diagnostic
      tests to detect it: insulin-like growth factor-1 deficiency and cell membrane
      pathology are an inevitable cause of heart disease.
AB  - Coronary heart disease (CHD) is a preventable disease with high morbidity and
      mortality. Largely omitted from the efforts at detection and treatment are the
      contributions of the lungs, the skeletal muscles and the arteries to heart
      disease pathology. Also omitted are the effects of the age-related decline in
      insulin-like growth factor-1 (IGF-1) and the age-related increase in cell
      membrane pathology. The hypothesis on which this model is based postulates that
      growing older, over time, necessarily results in pathological changes in the
      heart, the lungs, the skeletal muscles and the arteries. Additionally, the age
      related decline in (IGF-1) that occurs in the otherwise healthy aged population
      also causes similar pathological changes. The drug portion of the proposed
      treatment includes the use of the drug acetyl-l-carnitine (ALC) to increase the
      age-related decreased IGF-1 levels. The drug centrophenoxine (CPH) is used to
      reverse the age-related pathological changes that inevitably occur in the heart,
      the lungs, the skeletal muscles and the arteries. A testing procedure is included
      to improve the detection of heart disease and to monitor the results. It consists
      of five tests: the monitoring of plasma IGF-1 levels; the monitoring of blood
      pressure, and in particular elevated systolic blood pressure; the monitoring of
      blood pressure variability over time; a heart rate recovery time test and a heart
      rate reserve test. Heart rate reserve is defined as the difference between
      maximal heart rate and resting heart rate, after treadmill exercise. The changes
      in test results noted during treatment are an indicator of progress or
      deterioration in the prevention of heart disease, whatever the case may be.

PMID- 16412586
TI  - Discriminating signal from noise: recognition of a movement-based animal display
      by artificial neural networks.
AB  - In this study, we investigated the feasibility of applying neural networks to
      understanding movement-based visual signals. Networks based on three different
      models were constructed, varying in their input format and network architecture:
      a Static Input model, a Dynamic Input model and a Feedback model. The task for
      all networks was to distinguish a lizard (Amphibolurus muricatus) tail-flick from
      background plant movement. Networks based on all models were able to distinguish
      the two types of visual motion, and generalised successfully to unseen exemplars.
      We used curves defined by the receiver-operating characteristic (ROC) to select a
      single network from each model to be used in regression analyses of network
      response and several motion variables. Collectively, the models predicted that
      tail-flick efficacy would be enhanced by faster speeds, greater acceleration and
      longer durations.

PMID- 16412587
TI  - Visual co-orientation and expectations about attentional orientation in pileated
      gibbons (Hylobates pileatus).
AB  - This study investigated attentional processes in a sample of captive gibbons. An
      initial aim of the research was to examine subjects' ability to co-orient with
      photographic images of both conspecific and human models. The gibbons'
      expectancies about the focus of another's attention was then also assessed, with
      an expectancy violation paradigm revealing subjects' sensitivity to an
      incompatibility between visual orientation and the position of a target object.
      The gibbons were exposed to two conditions; consistent sequences in which the
      stimulus individual directed attention towards a target object, and inconsistent
      sequences in which the model's attentional focus was incompatible with the
      location of this article. Analyses of the subjects' responses were made according
      to the direction of gazes and the time spent inspecting the depicted model in
      each of these conditions. The results reveal a tendency for visual co-orientation
      with both conspecific and human models, suggesting that gibbons are competent in
      detecting the visual orientation of other species as well as their own.
      Furthermore, the subjects' tendency to look longer and check back to the depicted
      model in response to violations in the relationship between an agent and object
      (target appearing in an opposite direction to model's gaze), suggests that they
      possess some knowledge of how visual gaze direction relates to external stimuli.

PMID- 16412589
TI  - Genome and RNA: Expression and Functions. Papers presented at a symposium in
      Puentarenas, Costa Rica, 26 February-2 March 2005.

PMID- 16412588
TI  - PANDER-induced cell-death genetic networks in islets reveal central role for
      caspase-3 and cyclin-dependent kinase inhibitor 1A (p21).
AB  - PANcreatic DERived factor is an islet-specific cytokine that promotes apoptosis
      in primary islets and islet cell lines. To elucidate the genetic mechanisms of
      PANDER-induced cell death we performed expression profiling using the mouse
      PancChip version 5.0 in conjunction with Ingenuity Pathway Analysis. Murine
      islets were treated with PANDER and differentially expressed genes were
      identified at 48 and 72 h post-treatment. 64 genes were differentially expressed
      in response to PANDER treatment. 22 genes are associated with cell death. In
      addition, the genes with the highest fold change were linked with cell death or
      apoptosis. The most significantly affected gene at 48 h was the downregulated
      cyclin-dependent kinase inhibitor 1A (CDKN1A or p21). Approximately half of the
      genes impacted at 72 h were linked to cell death. Cell death differentially
      expressed genes were confirmed by quantitative RT-PCR. Further analysis
      identified cell death genetic networks at both time points with 21 of the 22 cell
      death genes related in various biological pathways. Caspase-3 (CASP3) was
      biologically linked to CDKN1A in several genetic networks and these two genes
      were further examined. Elevated cleaved CASP3 levels in PANDER-treated beta-TC3
      insulinoma cells were found to abrogate CDKN1A expression. Levels of CDKN1A were
      not affected in the absence of cleaved CASP3. PANDER-induced downregulation of
      CDKN1A expression coupled with induced CASP3-activation may serve a central role
      in islet cell death and offers further insight into the mechanisms of cytokine
      induced beta-cell apoptosis.

PMID- 16412590
TI  - Characterization of Asxl1, a murine homolog of Additional sex combs, and analysis
      of the Asx-like gene family.
AB  - The Additional sex combs (Asx) gene of Drosophila is required to maintain
      homeotic gene activation and silencing. Here we characterize the three murine
      homologs of Asx: Additional sex combs-like (Asxl1, Asxl2, and Asxl3) and identify
      conserved sequence features. The predicted amino acid sequence of Asxl1 has 16%
      identity and 40% similarity to Drosophila Asx, and 74% identity and 81%
      similarity to human ASXL1. Murine Asxl1 contains two regions highly conserved
      with Drosophila Asx: 1) a conserved amino terminal region of unknown function,
      termed the ASX homology domain (ASXH) which contains two nuclear receptor (NR) co
      regulator binding motifs; and 2) a conserved C-terminal PHD domain. The mammalian
      Asx-like predicted proteins possess additional conserved sequence features of
      unknown function not present in Drosophila Asx, including three more NR co
      regulator binding motifs. Asxl1and Asxl2 are expressed as multiple transcripts,
      at varying levels, in adult tissues and in embryonic stem cells analyzed by
      Northern blot, and exhibit similar expression patterns suggesting they may be co
      regulated. Whole mount RNA in situ hybridization revealed that Asxl1 is also
      expressed in 10.5-11.0 dpc mouse embryos.

PMID- 16412592
TI  - Immunosuppressive effects of rutaecarpine in female BALB/c mice.
AB  - Rutaecarpine is a major quinazolinocarboline alkaloid isolated from Evodia
      rutaecarpa. It was reported to possess a wide spectrum of pharmacological
      activities, such as vasodilation, antithrombosis, and anti-inflammation. In the
      present study, adverse effects of rutaecarpine on immune functions were
      determined in female BALB/c mice. Rutaecarpine had no effects on hepatotoxicity
      parameters in mice, as measured by serum activities of aminotransferases.
      Meanwhile, rutaecarpine significantly decreased the number of antibody-forming
      cells and caused weight decrease in spleen in a dose-dependent manner, when mice
      were administered with rutaecarpine at 10mg/kg, 20mg/kg, 40 mg/kg or 80 cmg/kg
      once intravenously. In addition, rutaecarpine administered mice exhibited reduced
      splenic cellularity, decreased numbers of total T cells, CD4(+) cells, CD8(+)
      cells, and B cells in spleen. IL-2, interferon-gamma and IL-10 mRNA expressions
      were suppressed significantly by rutaecarpine treatment. The number of CD4(+)IL
      2(+) cells was reduced significantly following administration of mice with
      rutaecarpine. Furthermore, rutaecarpine caused the cell cycle arrest in G(0)+G(1)
      phase in a dose-dependent manner. Rutaecarpine caused significant inductions of
      hepatic cytochrome P450 (CYP) 1A, 2B, and 2E1 activities dose-dependently. In the
      splenic lymphocyte proliferation assay, rutaecarpine inhibited proliferation by
      LPS and Con A ex vivo, whereas it had no effects on in vitro proliferation. These
      results suggested that a single bolus intravenous injection of rutaecarpine from
      20mg/kg might cause immunosuppressive effects, and that rutaecarpine-induced
      immunosuppression might be mediated, at least in part, through the inhibition of
      cytokine production and cell cycle arrest in G(0)+G(1) phase, and caused possibly
      by mechanisms associated with metabolic activation.

PMID- 16412591
TI  - In vitro exposure of porcine prepubertal follicles to 4-chlorobiphenyl (PCB3) and
      its hydroxylated metabolites: effects on sex hormone levels and aromatase
      activity.
AB  - The present study was undertaken to investigate the endocrine disrupting activity
      of PCB3 and its hydroxylated metabolites 4-OH-PCB3 and 3,4-diOH-PCB3 in ovarian
      follicle cells derived from prepubertal animals with special emphasis on
      cytochrome P-450-dependent aromatase (CYP19). Aromatase activity was assayed
      simply by measuring the production of 17beta-estradiol in the culture medium
      after addition of the substrate (testosterone). Theca interna and granulosa cells
      were exposed in vitro to 6 ng/ml of test chemicals for 24, 48, 72 and 96 h. PCBs
      stimulated the conversion of testosterone to estradiol in all treatments. In
      addition, PCB3, and to a lesser extent its metabolites, decreased progesterone
      secretion by these cells. This increase in estradiol and simultaneous decrease in
      progesterone suggests that progesterone is converted to testosterone and further
      to estradiol. The rank order of potency in estradiol secretion was 3,4-diOH
      PCB3>4-OH-PCB3>PCB3. The non-steroidal aromatase inhibitor CGS 16949A abolished
      this stimulatory activity, and reduced estradiol levels in treatment and control
      groups below the control levels, verifying that the increased estradiol secretion
      by follicle cells was due to aromatase activity. We infer that: (1) metabolism of
      PCB3 does not protect against endocrine disruption and (2) the estrogenic effect
      of these compounds is due to stimulation of aromatase activity.

PMID- 16412593
TI  - A study of the uterine protein variations during the estrus cycle in the cow: a
      comparison with the serum proteins.
AB  - To investigate uterine protein changes during the estrus cycle in the bovine, 115
      pluriparous genital tracts and blood samples were collected from the abattoir in
      Urmia. Genital tracts were considered healthy based on gross examination of the
      uterus and uterine histopathological findings. The phase of the estrus cycle was
      determined by the examination of the structures present on the ovaries and the
      uterine tonicity. Of the collected samples, 24 were pro-estrus, 21 estrus, 24 met
      estrus and 46 diestrus. The uterus was incised and uterine fluid was collected by
      gentle scraping of the uterine mucosa with a curette. The total protein
      concentration, protein profiles (on agarose gel electrophoresis) in the uterine
      fluid were evaluated and compared with those of the serum. Total protein, alpha1,
      alpha2, beta1 and beta2 globulin values in the uterus were significantly higher
      than those of the serum (P<0.05), while, the albumin, gamma1 and gamma2 globulin
      values in the serum were higher than those of the uterus throughout the cycle.
      During pro-estrus, uterine fluid beta2 (1.96 g/dl) and serum gamma1 (1.07 g/dl)
      and gamma2 (1.27 g/dl) globulins were higher than those in the other phases of
      the cycle. During estrus, serum total protein was lower than the other phases
      (4.92 g/dl), which was considered to be due to a reduction in serum alpha1 (0.25
      g/dl), gamma1 (0.65 g/dl) and gamma2 (0.64 g/dl) globulins in this phase. In met
      estrus uterine fluid beta1 globulin was in the lowest (1.19 g/dl) and serum
      gamma2 globulin at a high level (1.24 g/dl). It was concluded that uterine
      proteins as well as serum proteins fluctuate during the estrus cycle and, except
      for the albumin and gamma globulins, its protein content is higher than the
      serum. During the follicular phase of the cycle uterine alpha globulins are
      higher than those in other phases, with an elevation in beta1 and a reduction in
      beta2 and gamma globulin values during estrus, which may reflect the preparation
      of the uterus for receiving spermatozoa for the conception in this phase.

PMID- 16412594
TI  - Experimental study of the GAS process for producing microparticles of
      beclomethasone-17,21-dipropionate suitable for pulmonary delivery.
AB  - In this study the micronization of beclomethasone-17,21-dipropionate (BECD), used
      as an inhaled steroid for the treatment of asthma, was studied using the gas
      antisolvent (GAS) process as a "green" alternative to pharmaceutical
      recrystallization. A systematic investigation of the influence of the key GAS
      process parameters: antisolvent addition rate (1, 50, 75 and 100 ml/min),
      temperature (25, 32.5, 40 and 52.5 degrees C), solute concentration (5, 25, 70
      and 100%), and agitation rate (500, 1000, 2000 and 3000 rpm) were investigated on
      particle morphology, size distribution, and crystallinity. It was found using
      scanning electron microscopy (SEM) and laser diffraction, that increasing the
      antisolvent addition rate and the agitation rate, while decreasing the
      temperature and solute concentration, led to a decrease in the steroids mean
      particle diameter. These parameters could be tuned to give a mean particle
      diameter of 1.8 microm, and an average mass median aerodynamic diameter (MMAD) of
      7.9 microm. High-performance liquid chromatography (HPLC) results showed the
      recrystallized BECD was purer than the non-processed material. The role of the
      solvent (acetone, methanol and ethanol) in the BECD crystal structure was
      investigated using X-ray diffraction (XRD), which showed acetone gave a more
      crystalline structure, hence having lower incorporation into the crystal
      structure. These results showed that the GAS process has the potential to produce
      steroid with powder properties suitable for inhalation therapy.

PMID- 16412597
TI  - Towards a "crime pollen calendar" - pollen analysis on corpses throughout one
      year.
AB  - A palynological study was carried out on 28 corpses brought in one year (June
      2003-May 2004) to the morgue of the Institute of Legal Medicine of Parma
      (Northern Italy). This preliminary research focuses on the date of death, which
      was known for all corpses examined. Pollen sampling and analyses were made with
      the first aim of comparing the pollen grains found on corpses with those diffused
      in the atmosphere in the region in the same season as the known date of death.
      Eyebrows, hair-line near the forehead, facial skin and nasal cavities were
      sampled. Most of the corpses had trapped pollen grains, with the exception of two
      December corpses. All pollen grains were found with cytoplasm and in a good state
      of preservation. In this way, a series of reference data was collected for the
      area where the deaths occurred, and we examined whether pollen grains on corpses
      could be an index of the season of death. To verify this hypothesis, the pollen
      analyses were compared with data reported in the airborne pollen calendars of
      Parma and the region around. Pollen calendars record pollen types and their
      concentrations in the air, month by month. The quantity of pollen recorded on
      corpses did not prove to be directly related to the quantity of pollen in the
      air. But qualitatively, many pollen types which are seasonal markers were found
      on corpses. Main corpse/air discrepancies were also observed due to the great
      influence that the local environmental conditions of the death scene have in
      determining the pollen trapped by a corpse. Qualitative plus quantitative pollen
      data from corpses appeared helpful in indicating the season of death. A
      preliminary sketch of a "crime pollen calendar" in a synthetic graphic form was
      made by grouping the corpse pollen records into three main seasons: A,
      winter/spring; B, spring/summer; C, summer/autumn. Trends match the general
      seasonal trend of pollen types in the air.

PMID- 16412595
TI  - Study of auditory function in patients with chronic obstructive pulmonary
      diseases.
AB  - This study was designed to measure auditory function in patients with chronic
      obstructive pulmonary diseases (COPDs) who generally suffer from chronic
      hypoxemia. Control and COPD subject groups received a battery of tests to assess
      overall hearing sensitivity and peripheral (end-organ and eighth-nerve) and brain
      stem auditory function, as well as blood-gas analysis. Results showed a
      statistically significant difference for all audiological measures between the
      control group and a COPD subgroup--the presumptive hypoxic subjects (partial
      oxygen tensions, PO2, <75 mm Hg). Correlation analyses of results from all
      subjects (regardless of PO2) also revealed significant covariance with PO2 for
      overall, RMS, amplitude of click-evoked otoacoustic emissions (RA), hearing
      threshold level, and auditory brain-stem response (ABR, I-V inter-peak latency).
      Chi2 or Fisher's exact tests were statistically significant for frequencies of
      cases classified according to a criterion PO2 of 70 mm Hg (putative critical O2
      for completely normal auditory function) and either hearing thresholds falling
      below or RA values above 1.5 standard deviations of the control-group means,
      respectively. However, chi2 was not significant for a comparable criterion of ABR
      I-V IPL. In general, clinically significant hearing loss was uncommon in COPD
      patients, and the observed effects represented relatively small changes in the
      auditory measures examined. Still, overall, changes were in the direction of
      poorer function, and these results suggest physiologically significant impact of
      chronic hypoxemia and the need for further study to evaluate thoroughly this
      medical condition as a potential risk factor for audio-vestibular dysfunction.

PMID- 16412596
TI  - Evaluation of the effect of Withania somnifera root extracts on cell cycle and
      angiogenesis.
AB  - In the Indian System of Medicine, the medicinal plant, Withania somnifera Dunal
      (Solanaceae) finds application for numerous ailments including cancer. This study
      explores the mechanism(s) underlying this property. The hydroalcoholic extract of
      the roots (WS) was partitioned between chloroform (WS-chloroform) and water (WS
      water). Further, WS-chloroform was fractionated (A1-A12) by reverse-phase column
      chromatography and their withanolide content was quantified by high-performance
      liquid chromatography (HPLC). Preliminarily, the anti-proliferative activity of
      all the extracts and fractions was screened against human laryngeal carcinoma
      (Hep2) cells by microculture tetrazolium assay (MTT). Two extracts (WS and WS
      chloroform) and three fractions (A4, A5 and A6) negatively affected Hep2
      viability at the concentration of 25 microg/ml and these were further
      investigated pharmacologically. Flow cytometry revealed cell cycle block and
      accumulation of hypoploid (sub G1) cells as the mode of anti-proliferative
      activity of all but A4. Their anti-angiogenic potential was investigated by a
      chickchorio-allantoic membrane (CAM) wherein a significant inhibition (p<0.0001)
      of vascular endothelium growth factor (VEGF), induced neovascularization was
      recorded. The effect was confirmed in vivo by mouse sponge implantation method.
      These findings suggest that the roots of Withania somnifera possess cell cycle
      disruption and anti-angiogenic activity, which may be a critical mediator for its
      anti-cancer action.

PMID- 16412598
TI  - Bone and aging: effects on the maxillofacial skeleton.
AB  - The originally balanced system of normal bone metabolism with an equilibrium of
      bone resorption and bone formation experiences involutionary changes along with
      increasing age. This article provides an overview on the effects of aging on
      bone, in particular on the bone of the maxillofacial skeleton. It explains
      differences between the postmenopausal type and the senile type of osteoporosis,
      deals with age-related morphologic changes of bone, mechanisms leading to age
      related changes, depicts bones at high fracture risk in aging persons, analyses
      the reduced bone quantity and quality in cranial bone, and discusses the
      preservation of maxillofacial bone dimensions by implants. Therefore, research on
      wound healing, in particular bone healing, and on the regenerative potential of
      tissue of mesenchymal origin is of major interest and will eventually translate
      into improved care for patients during daily clinical routine.

PMID- 16412599
TI  - Adolescent melanoma: risk factors and long term survival.
AB  - AIMS: To report the adolescent melanomas with focus on differences in clinical
      characteristics, prognostic factors, disease free (DFS) and overall survival (OS)
      in comparison with adults. METHODS: A single institution retrospective study in
      which 49 adolescent patients were compared to an adult group of 972 patients. The
      10-year DFS, 10-year OS and prognostic factors were calculated for both groups.
      RESULTS: The median age for the adolescent patients was 17 (range 12-19) years
      and 49 (range 20-93) years for the adult patients. Median follow-up time was 92
      (range 4-366) months. Adolescent patients presented more often with locally
      advanced melanoma (p<0.01). The median Breslow thickness was 1.6 vs 2.0mm for the
      adults (p=0.075). Increasing age, ulceration, Breslow thickness, tumour location,
      male gender and stage at diagnosis were calculated to be negative prognostic
      factors for the adult group. In the adolescent group, only the stage at diagnosis
      was a significant negative predictor. The 10-year DFS and OS for the adolescent
      patients and adult group were not significantly different regarding AJCC stages I
      III. CONCLUSION: Although adolescent patients presented more often with locally
      advanced disease, there are no significant differences in the 10-year DFS and OS
      between adolescent and adult patients. In our series, we could not confirm the
      prognostic factors found in the adult group for the adolescent patients, except
      for the stage at diagnosis.

PMID- 16412600
TI  - Prognostic relevance of occult tumour cells in lymph nodes in colorectal cancer.
AB  - AIMS: Presently, in Europe the treatment of node-negative colorectal cancer (CRC)
      patients consists of surgical resection of the primary tumour without adjuvant
      systemic therapy. However, up to 30% of these patients will develop disease
      recurrence. These high-risk patients are possibly identified by occult tumour
      cell (OTC) assessment in lymph nodes. In this paper, studies on the clinical
      relevance of OTC in lymph nodes are reviewed. METHODS: A literature search was
      conducted in the National Library of Medicine by using the keywords colonic,
      rectal, colorectal, neoplasm, adenocarcinoma, cancer, lymph node, polymerase
      chain reaction, mRNA, immunohistochemistry, micrometastases and isolated tumour
      cells. Additional articles were identified by cross-referencing from papers
      retrieved in the initial search. RESULTS: The upstaging percentages through OTC
      assessment and the prognostic relevance of OTC in lymph nodes vary among studies,
      which is related to differences in techniques used to detect OTC. CONCLUSIONS: We
      conclude that OTC examination techniques should be standardized to illuminate
      whether OTC in lymph nodes can reliably identify high-risk node-negative
      patients.

PMID- 16412601
TI  - Sentinel node biopsy in patients with breast cancer--evaluation of exposure to
      radiation of medical staff.
AB  - AIM: To measure the absorbed doses of radiation to hands of medical staff
      performing sentinel node biopsy in breast cancer patients. METHODS: The study was
      conducted in 2004, during sentinel node biopsies in 13 breast cancer patients
      (T1/T2N0). Sentinel nodes were identified with the use of combined
      radiotracer/blue dye technique (lymphoscintigraphy--99mTc on albumin carrier,
      surgery after 24 h; blue dye; intraoperative detection of gamma radiation).
      Highly sensitive thermoluminescent dosimeters (TLD) made of LiF were used to
      assess the absorbed doses of radiation during the procedure. During
      lymphoscintigraphy and during surgical procedure a total of 57 TLDs was placed on
      different parts of hands of medical staff. RESULTS: Maximal dose recorded during
      lymphoscintigraphy by TLDs placed on the hands of the physician injecting the
      radiotracer was 164 microSv. Mean recorded doses were higher for non-dominant
      hand, especially for distal parts of the index finger, third finger and thumb.
      During the surgical procedure, TLDs placed on the hands of medical staff recorded
      much lower doses of radiation than during lymphoscintigraphy. The highest dose
      was recorded by TLD placed on the pulp of the dominant hand index finger (22
      microSv) of the operating surgeon. Mean doses recorded by TLDs placed on the
      hands of the operating surgeon ranged from 2 to 8 microSv. The absorbed dose of
      radiation to hands of the scrub nurse was similar to that absorbed to hands of
      the operating surgeon. CONCLUSION: The maximum recorded dose during sentinel node
      biopsy in this study was 2200 times smaller than current 1-year dose limit.

PMID- 16412602
TI  - The significance of one positive axillary node.
AB  - AIMS: The aim of this study was to identify a subgroup of patients with breast
      cancer that can safely avoid axillary dissection. METHODS: Using data collected
      by the Eindhoven Cancer Registry, we compared the clinico-pathological features
      of 489 patients with only one positive lymph node to those of 817 patients with
      more than one positive lymph node in the axilla. All patients underwent complete
      axillary dissection, not preceded by a sentinel node biopsy. RESULTS: Tumour size
      greater than 1cm, harvesting more than 15 axillary lymph nodes at
      histopathological examination, metastasis size larger than 2mm, extranodal
      extension, and nodal involvement of the axillary apex are independently
      associated with the occurrence of more than one metastatic axillary lymph node.
      CONCLUSION: No subgroup could be identified in which axillary dissection can
      always be omitted. However, tumour size<1cm, finding a micrometastasis rather
      than a macrometastasis, and especially not finding extranodal extension were
      independently associated with finding only one positive axillary lymph node.

PMID- 16412604
TI  - Evaluation of sentinel node identification with isosulfan blue in gastric cancer.
AB  - AIMS: The aim of this study was to clarify whether the metastasis of gastric
      cancer can be detected by identifying the sentinel lymph nodes (SNs) using only
      lymphatic dye. METHOD: The study was based on 101 patients clinically diagnosed
      with T1 and T2 gastric cancer. Isosulfan blue was intraoperatively injected
      within the submucosal layer around the lesion through an endoscope and blue
      stained nodes (BNs) were identified as SNs and harvested. Standard radical
      gastrectomy with D2 lymphadenectomy was performed on all patients and SNs and
      other nodes were evaluated. RESULTS: Out of 101 patients, 21 had lymph-node
      metastases. The accuracy of SN identification was 97.0% (98/101) and the
      metastasis detection rate was 85.7% (18/21). With improvement of the manoeuvre in
      the latter 84 cases, the detection rate was elevated up to 100.0% (18/18), as was
      the accuracy (84/84). CONCLUSION: The sentinel concept using lymphatic dye is
      applicable to gastric cancer, but the identification of SNs with lymphatic dye
      requires some practice. Furthermore, the issue of intraoperative metastasis
      detection remains to be resolved.

PMID- 16412603
TI  - Surgical treatment of primary locally advanced rectal cancer in Norway.
AB  - AIMS: Most reports on locally advanced rectal cancer come from specialized
      centres, with a selected patient material. The purpose of this study was to
      examine the results after surgical treatment of patients with locally advanced
      rectal cancer at a population level. METHODS: National cohort study of 896
      patients undergoing surgery for a locally advanced primary adenocarcinoma of the
      rectum from November 1993 to December 2001. RESULTS: Surgery with resection was
      undertaken in 724 patients and 172 patients underwent palliative procedures. Of
      557 patients treated for cure, a R0 resection was achieved in 342 (61%). In a
      multivariate analysis, pre-operative radiotherapy was the only factor with a
      positive association with R0 status (odds ratio 3.7, 95% confidence interval (CI)
      2.1-6.4). Five-year local recurrence rates were 18% (CI 14-23) for R0 resections
      and 40% (CI 26-52) for R1 resections. Overall 5-year survival rate was 23%; for
      the group of patients with a R0 resection the survival rate was 49%. CONCLUSION:
      The radical resection rate and survival rates in this national study were similar
      to those reported from specialized centres.

PMID- 16412605
TI  - Repeat isolated limb perfusion with TNFalpha and melphalan for recurrent limb
      melanoma after failure of previous perfusion.
AB  - AIM: To assess the effectiveness of isolated limb perfusion (ILP) with tumour
      necrosis factor-alpha (TNFalpha) and melphalan for recurrent or persistent
      melanoma lesions after previous ILP. METHODS: Between 1978 and 2001, 21 patients
      (mean age 65, range 29-83 years) underwent repeat ILP for recurrent or persistent
      melanoma after a previous ILP. First ILPs had been performed with melphalan alone
      in 13 patients and with addition of TNFalpha in eight, for a median of nine
      lesions (interquartile (IQ) range 2-23 lesions). Repeat ILP was performed with
      TNFalpha and melphalan in all 21 patients for a median of nine lesions (IQ range
      5-25 lesions). Median follow-up after repeat ILP was 18 months (IQ range 6-36
      months). RESULTS: Thirteen patients attained a complete response (CR) after
      repeat ILP compared to 11 of 17 with measurable lesions after the first ILP. Nine
      patients relapsed after CR. Median limb recurrence-free survival was 13 months.
      Fourteen patients had mild acute regional toxicity after repeat ILP compared to
      18 after the first ILP (n.s.). One patient underwent amputation for critical limb
      ischemia 10 months following repeat ILP. The limb salvage rate was 95%. Overall
      median survival was 62 months after CR compared to 13 months for those without CR
      (P=0.05). CONCLUSION: Repeat ILP with TNFalpha and melphalan is feasible after
      previous ILP with mild regional toxicity. The CR rate is relatively high and
      comparable to the first procedure with good limb recurrence-free survival and
      high limb salvage rate.

PMID- 16412606
TI  - FGFR3 and p53 protein expressions in patients with pTa and pT1 urothelial bladder
      cancer.
AB  - AIMS: This study is designed to evaluate the expression and prognostic value of
      FGFR3 protein expression in patients with pTa/pT1 tumours and to determine the
      significance of the combinations of FGFR3 and p53 protein expressions in bladder
      pathogenesis. MATERIALS AND METHODS: A tissue microarray (TMA) of 107 pTa, and
      147 pT1 tumours was constructed. The TMA sections were immunostained with FGFR3
      and p53 monoclonal antibodies. RESULTS: There were significant associations
      between loss of FGFR3 and tumour stage (p<0.001) and grade (p<0.001) and between
      p53 overexpression and tumour stage and grade (p<0.001 and p<0.001,
      respectively). There was no association between FGFR3 and p53 proteins (p=0.107).
      In addition, tumours with FGFR3+/p53- phenotype have slower recurrence rate than
      other (FGFR3+/p53+, FGFR3-/p53- and FGFR3-/p53+). CONCLUSION: 1-FGFR3 expression
      is significantly associated with two important prognostic factors; stage and
      grade. 2-FGFR3 protein expression is not an independent predictive factor for
      pTa/pT1 tumour recurrence and progression. 3-Tumours with FGFR3+/p53- phenotype
      seem to have a distinctive pathway in bladder tumorigenesis.

PMID- 16412607
TI  - Ferric iron increases ROS formation, modulates cell growth and enhances genotoxic
      damage by 4-hydroxynonenal in human colon tumor cells.
AB  - Iron is a relevant risk factor for colorectal cancer due to its genotoxic
      properties. Here we hypothesised that iron-overload causes other toxic effects,
      which contribute to carcinogenesis. For this, we investigated formation of
      reactive oxygen species (ROS), DNA repair, cell growth and glutathione (GSH) in
      human colon tumor cells (HT29 clone 19A) treated with ferric nitrilotriacetate
      (Fe-NTA, 0-2000 microM). Intracellular formation of ROS was analysed with the
      peroxide-labile fluorescent dye carboxy-dichlorodihydrofluorescine-diacetate. DNA
      repair, reflected as the persistency of DNA damage induced by selected
      genotoxins, was determined with the Comet assay. Cell growth and GSH were
      measured by fluorimetrical analysis. Key findings were that ROS formation
      increased with time (1000 microM Fe-NTA, p < 0.001). DNA damage was largely
      repaired after 120 min, but was not affected by 10 microM Fe-NTA. In contrast, 10
      microM Fe-NTA significantly increased DNA damage induced by 4-hydroxynonenal.
      Doses of 25 microM Fe-NTA increased cell growth (p < 0.05), whereas high
      concentrations (2000 microM) resulted in growth arrest (p < 0.05), that was
      accompanied by increased GSH levels (p < 0.01). In conclusion, high
      concentrations of Fe-NTA caused cellular effects, which reflect a stress
      response, and resulted in formation of ROS. Carcinogenic risks from ferric iron
      could be derived also from lower concentrations, which enhance tumor cell growth
      and cause progenotoxic effects.

PMID- 16412608
TI  - Subjective social status moderates cortisol responses to social threat.
AB  - Research has demonstrated a robust relationship between social status, physiology
      and health in humans and animals. However, perceptions of social status within a
      specific social group have rarely been studied in this area and may provide
      additional relevant information. The current investigation examines subjective
      perceptions of social status as a moderator of cognitive, emotional and cortisol
      responses to stressor tasks characterized by social-evaluative threat or its
      absence. As part of a larger study, 81 college students living in a residential
      dormitory completed a measure of their subjective perceptions of their social
      status within their dormitory floor. They were randomly assigned to undergo a
      standard performance stressor task either with or without social evaluation. It
      was hypothesized that individuals who perceived that they were of low status
      within their dorm group would show greater increases in negative self-evaluative
      emotions (i.e., shame) and cognitions (low social self-esteem) and greater
      cortisol responses to the stressor under conditions of social-evaluative threat.
      Subjective social status moderated cortisol responses to the social-evaluative
      stressor, but in a direction opposite that hypothesized. Individuals who
      perceived themselves to be of high status showed sizable and significant cortisol
      increases (both peak and recovery), while those who perceived themselves to be of
      low status did not mount a significant cortisol response to the stressor. Both
      groups showed increased negative self-evaluative responses to the tasks. A
      discussion of the possible health implications of the robust cortisol responses
      of high status individuals and the hyporesponsive cortisol reactions of low
      status individuals is provided.

PMID- 16412609
TI  - Heart rate and the role of the active receiver during contingent electric shock
      for severe self-injurious behavior.
AB  - Five individuals, who were treated for severe self-injurious behaviors with
      contingent electric shock, participated. Hereby, each occurrence of the target
      response was followed by a remotely administered aversive consequence.
      Participants' heart rates were compared at times when the active device of the
      equipment for the above procedure was attached to their body and when the active
      device was detached. Although typical response patterns emerged across the
      participants results demonstrated that heart rates were lower when the active
      device was attached, tentatively supporting the notion that anxiety and stress
      may be collateral to participants' SIB.

PMID- 16412610
TI  - Effects of Concord grape juice on cognitive and motor deficits in aging.
AB  - OBJECTIVE: Animals and humans show increased motor and cognitive declines with
      aging that are thought to be due to increased susceptibility to the long-term
      effects of oxidative stress and inflammation. Previous findings have suggested
      that reversals in these age-related declines might be accomplished by increasing
      the dietary intake of polyphenolics found in fruits and vegetables, especially
      those identified as being high in antioxidant and anti-inflammatory activities.
      METHODS: We investigated the beneficial effects of two concentrations of Concord
      grape juice (10% and 50%) compared with a calorically matched placebo for their
      effectiveness in reversing age-related deficits in behavioral and neuronal
      functions in aged Fischer 344 rats. RESULTS: Rats that drank the 10% grape juice
      from age 19 to 21 mo had improvements in oxotremorine enhancement of K+-evoked
      release of dopamine from striatal slices and in cognitive performance on the
      Morris water maze, and the 50% grape juice produced improvements in motor
      function. CONCLUSIONS: These findings suggest that, in addition to their known
      beneficial effects on cancer and heart disease, polyphenolics in foods may be
      beneficial in reversing the course of neuronal and behavioral aging, possibly
      through a multiplicity of direct and indirect effects that can affect a variety
      of neuronal parameters.

PMID- 16412611
TI  - Postprandial glycogen and lipid synthesis in prednisolone-treated rats maintained
      on high-protein diets with varied carbohydrate levels.
AB  - OBJECTIVE: The present experiment was designed to study the effect of a high
      protein, high-carbohydrate diet versus a high-protein, low-carbohydrate diet on
      in vivo postprandial glycogen and lipid synthesis of rats treated with
      prednisolone. METHODS: Thirty-two 6-wk-old male Sprague-Dawley rats were randomly
      assigned to one of four equal groups: high-protein, high-carbohydrate; high
      protein, high-carbohydrate with prednisolone; high-protein, low-carbohydrate; and
      high-protein, low-carbohydrate with prednisolone. Rats were sham operated or
      subcutaneously implanted with prednisolone pellets while being maintained on
      their respective diets (39% of energy from protein) for 6 wk. Food intake and
      body weight were monitored throughout the experiment. At the end of the feeding
      period, overnight-fasted rats were fed a test meal and injected with 3H2O to
      measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose,
      insulin, and triacylglycerol concentrations and hepatic glycogen content were
      also measured. RESULTS: Results showed that hepatic glycogen content (milligrams
      per gram of liver) was similar across all four experimental groups. Total hepatic
      glycogen synthesis and its percentage synthesis via pyruvate (indirect pathway)
      were higher in rats maintained on the high-protein, high-carbohydrate diet
      compared with those on the high-protein, low-carbohydrate diet and this was not
      substantially affected by prednisolone administration. Hepatic and epididymal fat
      pad lipid syntheses were not altered by diet or prednisolone treatments.
      CONCLUSION: Under long-term high-protein conditions, prednisolone administration
      does not seem to affect hepatic glycogen synthesis, which was increased with the
      increased carbohydrate content of the diet.

PMID- 16412612
TI  - Development of visual motion perception in children of patients with
      schizophrenia and bipolar disorder: a follow-up study.
AB  - The "dorsal-stream vulnerability" hypothesis claims that motion-sensitive areas
      in the dorsal occipito-parietal visual system are vulnerable to genetic and
      environmental factors which affect brain maturation and development. The aim of
      this study was to investigate the possibility that developmental anomalies of
      directional motion perception can be detected in children of mothers with
      schizophrenia and bipolar disorder. Motion and form coherence thresholds were
      measured in 36 children of mothers with schizophrenia, 28 children of mothers
      with bipolar disorder, and 30 children with negative family history at 7, 8-9,
      and 10-11 years of age. These tasks require the detection of direction of
      coherently moving dots embedded among randomly oscillating dots (motion task) and
      the detection of tangentially oriented line-segments embedded among randomly
      oriented segments (form task). Results revealed that the rate of development in
      the motion task was less pronounced in children of mothers with schizophrenia
      than that in children of mothers with bipolar disorder and in age-matched
      controls. The development of form perception was spared. Children of mothers with
      bipolar disorder showed an intact development in both motion and form perception
      tasks. These results suggest that the progressive developmental abnormality of
      motion-sensitive visual areas may be a characteristic feature of schizophrenia
      vulnerability.

PMID- 16412613
TI  - Role of substance P in stress-derived degranulation of dermal mast cells in mice.
AB  - BACKGROUND: The interaction between nerves and mast cells can effect regulation
      of the immune system and inflammatory responses. Recent studies have shown that
      various stressors can induce degranulation of dermal mast cells in animals.
      OBJECTIVES: This study was conducted to confirm that substance P (SP) was
      involved in the degranulation of dermal mast cells in stress conditions. METHODS:
      Using a communication box system, foot shock stress (FS) and psychological stress
      (PS) were administered to mice and the degranulation rate of dermal mast cells,
      the number of SP-positive nerve fibers and changes in SP content were determined.
      The inhibitory effect of a non-peptide NK1-receptor antagonist on these changes
      was investigated. RESULTS: Both FS and PS significantly enhanced the
      degranulation of dermal mast cells and increased the number of SP-positive nerve
      fibers. FS significantly decreased dermal SP content whereas SP was increased by
      PS. These changes were inhibited by intraperitoneal injection of NK(1) receptor
      antagonist. CONCLUSIONS: It was considered that SP released from the nerve
      ending, had an important role in the degranulation of dermal mast cells. Results
      of this study suggest that the tachykinin receptor antagonist exhibited an
      inhibitory effect on aggravated stress-induced dermatitis.

PMID- 16412614
TI  - Transcriptional profiling implicates TGFbeta/BMP and Notch signaling pathways in
      ductular differentiation of fetal murine hepatoblasts.
AB  - Bile duct morphogenesis involves sequential induction of biliary specific gene
      expression, bilayer generation, cell proliferation, remodeling and apoptosis. HBC
      3 cells are a model system to study differentiation of hepatoblasts along the
      hepatocytic or bile ductular lineage in vitro and in vivo. We used microarray to
      define molecular pathways during ductular differentiation in response to
      Matrigel. The temporal pattern of expression of marker genes induced was similar
      to that observed during bile duct formation in vivo. Notch, HNF1beta, Polycystic
      kidney disease 2, Bicaudal C 1 and beta-catenin were up regulated during the time
      course. Functional clustering analysis revealed significant up regulation of
      clusters of genes involved in extracellular matrix remodeling, ion transport,
      vacuoles, lytic vacuoles, pro-apoptotic and anti-apoptotic genes, transcription
      factors and negative regulators of the cell proliferation, while genes involved
      in the cell cycle were significantly down regulated. Notch signaling pathway was
      activated by treatment with Matrigel. In addition, TGFbeta/BMP signaling pathway
      members including the type I TGFbeta receptor and Smads 3, 4 and 5 were
      significantly up regulated, as were several TGFbeta/BMP responsive genes
      including Hey 1, a regulator of Notch pathway signaling. SMADS 3, 4 and 5 were
      present in the nuclear fraction of HBC-3 cells during ductular differentiation in
      vitro, but not during hepatocyte differentiation. SMAD 5 was preferentially
      expressed in hepatoblasts undergoing bile duct morphogenesis in the fetal liver,
      while the TGFbeta/BMP signaling antagonist chordin, was expressed throughout the
      liver suggesting a mechanism by which TGFbeta/BMP signaling is limited to
      hepatoblasts that contact portal mesenchyme in vivo.

PMID- 16412615
TI  - Smoothened, thickveins and the genetic control of cell cycle and cell fate in the
      developing Drosophila eye.
AB  - The Hedgehog and Decapentaplegic pathways have several well-characterized
      functions in the developing Drosophila compound eye, including initiation and
      progression of the morphogenetic furrow. Other functions involve control of cell
      cycle and cell survival as well as cell type specification. Here we have used the
      mosaic clone analysis of null mutations of the smoothened and thickveins genes
      (which encode the receptors for these two signals) both alone and in combination,
      to study cell cycle and cell fate in the developing eye. We conclude that both
      pathways have several, but differing roles in furrow induction and cell fate and
      survival, but that neither directly affects cell type specification.

PMID- 16412616
TI  - Functional analysis of chick ONT1 reveals distinguishable activities among
      olfactomedin-related signaling factors.
AB  - The Olfactomedin family is a relatively new class of extracellular proteins. Two
      family members have been shown to play roles in the early development of
      ectodermal tissues: Noelin enhances neural crest generation in chick and Tiarin
      promotes dorsal neural specification in Xenopus. In this study, we introduce a
      novel member of the Olfactomedin family, ONT1. In the early chick embryo, ONT1
      expression first appears at Hensen's node and subsequently in the axial and
      paraxial mesoderm. When the neural tube closes, strong expression of ONT1 is
      transiently found in the roof plate region from the rostral midbrain to the
      hindbrain. Overexpression of ONT1 in these regions prolongs the generation of
      neural crest cells in a manner similar to that of Noelin. Interestingly, ONT1 and
      Noelin have opposing effects on the expression of the migrating neural crest
      marker HNK-1 in the chick: they, respectively, cause suppression and ectopic
      induction of this marker. Differential activities among Olfactomedin-related
      factors are further examined in Xenopus. Microinjection of ONT1 mRNA into the
      Xenopus embryo expands the expression domain of the neural crest marker FoxD3 at
      the neurula stage whereas overexpression of Tiarin or Noelin suppresses FoxD3.
      ONT1 exhibits no dorsalizing effects on the Xenopus neural tube, which contrasts
      with the strong dorsalizing activity seen for Tiarin. Thus, distinct Olfactomedin
      related factors evoke qualitatively different phenotypes even in the same
      experimental systems, suggesting that Olfactomedin family uses multiple response
      systems to mediate its signals in embryogenesis.

PMID- 16412617
TI  - Transcriptional upregulation of the C. elegans Hox gene lin-39 during vulval cell
      fate specification.
AB  - Extracellular signaling pathways and transcriptional regulatory networks function
      during development to specify metazoan cell fates. During Caenorhabditis elegans
      vulval development, the specification of three vulval precursor cells (VPCs)
      requires the activity of Wnt, Notch, and Ras signaling pathways, and function of
      the Hox gene lin-39. LIN-39 protein levels are regulated in the VPCs by both Wnt
      and Ras signaling. In particular, activation of Ras signaling leads to an
      increase in LIN-39 protein in P6.p at the time of VPC fate specification. We wish
      to understand the regulation of lin-39 by these pathways. We first show that LIN
      39 is a target for MAP kinase in vitro, suggesting that the Ras-dependent LIN-39
      upregulation could be mediated post-translationally. To test this idea, we
      created transcriptional and translational lin-39::GFP fusions that include the
      entire lin-39 genomic region, allowing observation of lin-39 expression in live
      animals. The reporters express GFP in most, if not all, sites of expression
      previously observed by LIN-39 antibody staining. We used these constructs to show
      that at the time of vulval induction both lin-39::GFP reporters are upregulated
      in P6.p, indicating that the accumulation of high levels of LIN-39 protein
      detected previously corresponds to transcriptional upregulation of lin-39
      expression. This transcriptional upregulation of lin-39 is dependent on Ras
      signaling. We tested the requirement for several transcription factors acting
      downstream of Ras signaling in the VPCs, and found that P6.p upregulation
      requires the transcription factors LIN-1 and LIN-25, but appears to be
      independent of LIN-31, SEM-4, EOR-1 and EOR-2.Finally, we found that when the Wnt
      pathway is over activated, expression from the transcriptional lin-39::GFP
      increases, suggesting that the Wnt pathway also regulates lin-39 at the
      transcriptional level.

PMID- 16412618
TI  - Genetic evidence does not support direct regulation of EDNRB by SOX10 in
      migratory neural crest and the melanocyte lineage.
AB  - Mutations in the transcription factor Sox10 or Endothelin Receptor B (Ednrb)
      result in Waardenburg Syndrome Type IV (WS-IV), which presents with deficiencies
      of neural crest derived melanocytes (hypopigmentation) and enteric ganglia
      (hypoganglionosis). As Sox10 and Ednrb are expressed in mouse migratory neural
      crest cells and melanoblasts, we investigated the possibility that SOX10 and
      EDNRB function through a hierarchical relationship during melanocyte development.
      However, our results support a distinct rather than hierarchical relationship.
      First, SOX10 expression continues in Ednrb null melanoblasts, demonstrating that
      SOX10 expression is not dependent on EDNRB function. Second, Ednrb expression
      persists in E10.5 Sox10null embryos, demonstrating that Ednrb is not dependent on
      SOX10 for expression in migratory neural crest cells. Third, over-expression of
      SOX10 in melanoblasts of mice that harbor null or hypomorphic Ednrb alleles does
      not rescue hypopigmentation, suggesting that SOX10 overexpression can neither
      complement a lack of EDNRB function nor increase Ednrb expression. Fourth, mice
      that are double heterozygous for loss-of-function mutations in Sox10 and Ednrb do
      not demonstrate synergistically increased hypopigmentation compared to mice that
      are single heterozygotes for either mutation alone, suggesting a lack of direct
      genetic interaction between these genes. Our results suggest that SOX10 does not
      directly activate Ednrb transcription in the melanocyte lineage. Given that SOX10
      directly activates Ednrb in the enteric nervous system, our results suggest that
      SOX10 may differentially activate target genes based on the particular cellular
      context.

PMID- 16412619
TI  - Application of TPGS in polymeric nanoparticulate drug delivery system.
AB  - d-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) has great potential
      in pharmacology and nanotechnology. The present work investigated the molecular
      behaviour of TPGS at the air-water interface, its effect on a model bio-membrane
      composed of dipalmitoylphosphatidylcholine (DPPC) lipid monolayer, and the
      interaction between the TPGS coated nanoparticles with the lipid model membrane.
      Paclitaxel loaded polymeric nanoparticles with TPGS as surfactant stabiliser were
      fabricated and characterised in terms of their drug incorporation capability and
      release kinetics. The result showed that TPGS exhibited notable effect on the
      surface properties of air-water interface as well as the lipid monolayer. The
      inter-particle force and the interaction between nanoparticles and lipid
      monolayer varied with the surface substance. The penetration of various
      nanoparticles into the model membrane indicated that an optimal balance between
      hydrophilicity and hydrophobicity on nanoparticle surface is needed to achieve an
      effective cellular uptake of nanoparticles. The results also demonstrate that the
      drug incorporation capability and the release characteristics of drug-loaded
      nanoparticles can be influenced by surfactant stabiliser.

PMID- 16412620
TI  - Characterization of the Actinomyces naeslundii ureolysis and its role in
      bacterial aciduricity and capacity to modulate pH homeostasis.
AB  - Ammonia production from urea by ureolytic oral bacteria is believed to have a
      significant impact on oral health and ecological balance of oral microbial
      populations. Actinomyces naeslundii is an important ureolytic organism in the
      oral cavity. In this study, we aimed to investigate the substrate affinity and pH
      optimum for ureolysis of A. naeslundii (ATCC12104), and expression of urease
      under different environmental factors. In addition, in vitro acid killing and pH
      drop experiments were used to detect the role of ureolysis in bacterial
      aciduricity and capacity to modulate pH homeostasis. We observed the K(s) value
      of the ureolytic activity was 7.5mM and a pH optimum near 6.5. Urease expression
      by A. naeslundii (ATCC12104) was affected by multiple factors, including
      environmental pH, glucose and nitrogen availability. The cells could be protected
      against acid killing through hydrolysis of physiologically relevant
      concentrations of urea. A. naeslundii (ATCC12104) demonstrated a significant
      capacity to temper glycolytic acidification in vitro at urea concentrations
      normally found in the oral cavity.

PMID- 16412621
TI  - Spectroscopic characterization and identification of Pseudomonas fluorescens
      mediated metabolic products of Acid Yellow-9.
AB  - Pseudomonas flourescens NCIM 2100 was obtained from NCL, Pune, India, that was
      adapted to growth on 4 amino 1-1 azo benzene 3,4-Disulfonic acid. This strains
      was tested by UV, (1)H NMR, and IR spectroscopy for its ability to degrade the
      dye which resulted in to sulfonated analogs namely p-amino benzene sulfonic acid
      sodium salt and 2,4 diamino benzene sulfonic acid sodium salt. These compound
      further changed to either 2,4 dihydroxy benzene sulfonic acid sodium salt or 2
      amino 4 hydroxy benzene sulfonic acid sodium salt, or 4 amino 2 hydroxy benzene
      sulfonic acid sodium salt. These breakdown compounds were non toxic in nature.

PMID- 16412622
TI  - Differential effect of saturated, monounsaturated, and polyunsaturated fatty
      acids on alloxan-induced diabetes mellitus.
AB  - Earlier, we reported that oils rich in omega-3 eicosapentaenoic acid and
      docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid
      prevented the development of alloxan-induced diabetes mellitus in experimental
      animals. Here we report the results of our studies with pure saturated stearic
      acid (SA), monounsaturated oleic acid (OA) and omega-6 arachidonic acid (AA) on
      alloxan-induced diabetes mellitus in Wistar male rats. Prior oral supplementation
      with AA prevented alloxan-induced diabetes mellitus, whereas both SA and OA were
      ineffective. Cyclo-oxygenase (COX) and lipoxygenase (LO) inhibitors did not block
      this protective action of AA against alloxan-induced diabetes, suggesting that
      both prostaglandins and leukotrienes are not involved, and that AA by itself is
      effective. Furthermore, AA restored the anti-oxidant status to normal range in
      various tissues. These results suggest that AA protects pancreatic beta cells
      against alloxan-induced diabetes in experimental animals by attenuating oxidant
      stress.

PMID- 16412623
TI  - Systemic side effects of inhaled corticosteroids in patients with asthma.
AB  - Asthma is a complex disease of the respiratory tract associated with chronic
      inflammation in which an intricate network of cells and cellular factors plays a
      major role. Asthma is one of the most common chronic diseases, with an estimated
      300 million cases worldwide, imposing a considerable burden on society in
      morbidity, quality of life, and healthcare costs. Inhaled corticosteroids (ICSs)
      form the gold standard, first-line therapy in the effective management of
      persistent asthma and reduce morbidity and mortality from asthma. However, long
      term use of high-dose ICS therapy has potential to cause systemic side effects
      impaired growth in children, decreased bone mineral density, skin thinning and
      bruising, and cataracts. Hypothalamic-pituitary-adrenal-axis suppression,
      measured by serum or urine cortisol decrease, correlates with the occurrence of
      systemic side effects of high-dose ICSs. Therefore, cortisol may be a relevant
      surrogate marker to identify the potential for adverse effects from ICS therapy.
      Ciclesonide is a new generation ICS with demonstrable safety and efficacy in the
      treatment of asthma. The unique pharmacologic characteristics of ciclesonide,
      such as reduced local adverse effects, lack of cortisol suppression, and the
      option for once-daily dosing, may improve compliance with therapy and allow long
      term use of ICSs without fear of systemic adverse effects.

PMID- 16412625
TI  - Prior outpatient antibacterial therapy as prognostic factor for mortality in
      hospitalized pneumonia patients.
AB  - STUDY OBJECTIVES: To assess whether prior outpatient treatment is associated with
      outcome in patients hospitalized for community-acquired pneumonia (CAP). PATIENTS
      AND METHODS: All patients with a first hospital admission for CAP between 1995
      and 2000 were selected. Patients were divided into two groups, one of patients
      with use of antibacterial agents prior to hospitalization and one of patients
      treated as inpatient directly. The main outcome measures were duration of
      hospital stay and in-hospital mortality. RESULTS: The two patient groups
      comprised 296 and 794 patients, respectively. The median duration of hospital
      stay was 10 days and was similar for both groups. In patients with respiratory
      diseases or heart failure, the median duration of hospital stay was 12 and 14
      days, respectively. The overall in-hospital mortality was 7.2% and did not
      largely differ between both groups. In patients with congestive heart failure,
      the mortality was 9.8% for controls and 23.3% for patients hospitalized after
      initial outpatient treatment (adjusted OR 2.78, 95% CI 1.01-7.81). CONCLUSIONS:
      Prior outpatient antibacterial therapy is not associated with outcome in
      hospitalized pneumonia patients. In patients with underlying chronic heart
      failure, prior outpatient antibiotic is associated with a significant increased
      mortality.

PMID- 16412624
TI  - Prevalence of nutritional depletion in a large out-patient population of patients
      with COPD.
AB  - OBJECTIVE: The present study focuses on the prevalence of nutritional depletion
      in relation to functional performance, airflow limitation, experienced dyspnoea
      and health status in a large multi-center out-patient population with chronic
      obstructive pulmonary disease (COPD). METHODS: In 39 out-patient centers in The
      Netherlands, 389 patients with moderate to severe COPD (217 men) were recruited.
      The study evaluated on the baseline characteristics of the COSMIC study.
      Measurements included body composition by bioelectrical impedance analysis,
      dyspnoea by MRC-score, peripheral muscle function by isometric handgrip strength
      and disease-specific health status by St. George Respiratory Questionnaire.
      RESULTS: The prevalence of nutritional depletion (defined as body mass index
      (BMI)<or=21 kg/m2 and/or fat-free mass index (FFMI)<or=15 (females) or <or=16
      (males) kg/m2) was high (27%). Prevalence of normal BMI and low FFMI was 15%, and
      of low BMI and low FFMI 11%. The prevalence of low BMI as well as low FFMI was
      significantly higher in female than in male COPD patients, 18% and 40% vs. 10%
      and 20%, respectively (both P<0.01). No differences in FEV1%predicted, dyspnoea
      score and health status were observed between depleted and non-depleted COPD
      patients. Multiple linear regression analysis in the total group showed that
      handgrip strength correlated with FFMI after correction for sex distribution and
      age, but not FEV1%predicted. CONCLUSIONS: The prevalence of nutritional depletion
      was high in a large out-patient COPD population in The Netherlands, especially in
      female COPD patients. Depletion of FFM was associated with impaired peripheral
      muscle strength, independent of disease severity.

PMID- 16412626
TI  - Proceedings from the 3rd Intercontinental Landfill Research Symposium, Toya Lake,
      Japan, November 29-December 2, 2004.

PMID- 16412627
TI  - Evaluation of remedial countermeasures using the analytic network process.
AB  - The aim of this paper is to present an evaluation method to aid decision makers
      in the prioritization and selection of appropriate countermeasures at the
      planning stage of site remediation. We introduced a hierarchical network
      (hiernet) decision structure and applied the Analytic Network Process (ANP)
      supermatrix approach to measure the relative desirability of the remedial
      alternatives using the decision maker's value judgment as input. A simplified
      illustrative example is presented to elucidate the process, as it is being
      applied to evaluate the feasible remedial countermeasures of a contaminated site
      caused by uncontrolled landfill. Four decision models derived from the
      generalized hiernet were examined to describe the effect of hierarchic functional
      dependence, inner dependence and feedback cycle on the derivation of the priority
      weights. The ANP could provide a more flexible analytical framework to break down
      one's judgment through a more elaborate structure in a systematic way to
      understand the complexity of the decision problem. The proposed method therefore
      may not only aid in selecting the best alternative but also may help to
      facilitate communication to understand why an alternative is preferred over the
      other alternatives through the analysis of the derived weights and its underlying
      decision structure.

PMID- 16412628
TI  - Development of a disease-specific Quality of Life questionnaire module for
      patients with gastrointestinal neuroendocrine tumours.
AB  - Quality of life (QoL) measurements are increasingly being used as an end point in
      cancer clinical trials. Standard generic QoL questionnaires may not assess
      symptoms produced by neuroendocrine tumours. Here we report the development of a
      disease-specific quality of life score questionnaire for patients with
      neuroendocrine tumours of the gut to supplement the EORTC core cancer
      questionnaire, the QLQ-C30. Phases 1-3 of the EORTC quality of life group
      guidelines for module development were used to design the new questionnaire.
      Forty-one relevant issues (questions) were generated after an extensive
      literature search. Following interviews of 15 health care workers and 35
      patients, a 35 question provisional questionnaire was constructed. This was
      translated into seven European languages and pre-tested in 180 patients resulting
      in a 21-item module that will be validated in an international clinical trial.
      The EORTC QLQ-NET21 provides a site-specific module to supplement the QLQ-C30 for
      patients with neuroendocrine tumours.

PMID- 16412629
TI  - Survival in France after childhood acute leukaemia and non-Hodgkin's lymphoma
      (1990-2000).
AB  - This article describes the survival after childhood acute leukaemia (AL) and non
      Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French
      National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of
      acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and
      1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years
      were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML
      and NHL, respectively. Survival after AL increased from 77% (95% CI 75-80) in
      1990-1992 to 85% (95% CI 83-87) in 1997-2000 for ALL and from 47% (95% CI 41-54)
      to 61% (95% CI 55-67) for AML. Among AL cases, children aged 1-4 years had the
      most favourable prognosis. Down's syndrome was associated with poor survival
      after ALL. No gender-related variations in survival were in evidence. The results
      reported herein are similar to those reported by other European registries and
      clinical trials.

PMID- 16412630
TI  - Assessment of permeable covers for odour reduction in piggery effluent ponds. 2.
      Field-scale trials.
AB  - The efficacy of supported covers was investigated under field conditions using a
      series of prototypes deployed on an anaerobic pond treating typical piggery
      waste. Research focused on identifying effective cover support materials and
      deployment methods, quantifying odour reduction, and estimating the life
      expectancy of various permeable cover materials. Over a 10-month period, median
      odour emission rates were five to eight times lower from supported straw cover
      surfaces and a non-woven, spun fibre polypropylene weed control material than
      from the adjacent uncovered pond surface. While the straw covers visually
      appeared to degrade very rapidly, they continued to reduce odour emissions
      effectively. The polypropylene cover appeared to offer advantages from the
      perspectives of cost, reduced maintenance and ease of manufacture.

PMID- 16412631
TI  - The potential of restaurant waste lipids as biodiesel feedstocks.
AB  - Biodiesel is usually produced from food-grade vegetable oils that are more
      expensive than diesel fuel. Therefore, biodiesel produced from food-grade
      vegetable oil is currently not economically feasible. Waste cooking oils,
      restaurant grease and animal fats are potential feedstocks for biodiesel. These
      inexpensive feedstocks represent one-third of the US total fats and oil
      production, but are currently devoted mostly to industrial uses and animal feed.
      The characteristics of feedstock are very important during the initial research
      and production stage. Free fatty acids and moisture reduce the efficiency of
      transesterification in converting these feedstocks into biodiesel. Hence, this
      study was conducted to determine the level of these contaminants in feedstock
      samples from a rendering plant. Levels of free fatty acids varied from 0.7% to
      41.8%, and moisture from 0.01% to 55.38%. These wide ranges indicate that an
      efficient process for converting waste grease and animal fats must tolerate a
      wide range of feedstock properties.

PMID- 16412632
TI  - BACE-1 inhibitory activities of new substituted phenyl-piperazine coupled to
      various heterocycles: chromene, coumarin and quinoline.
AB  - The protease beta-secretase plays a central role in the synthesis of pathogenic
      amyloid-beta in Alzheimer's disease. Here, we report a new series of analogues
      based on the phenyl-piperazine scaffold coupled to various heterocyclic moieties,
      which demonstrate improved inhibitory activities on BACE-1 (FRET assay) compared
      to already known naphthyl counterparts. The obtained results suggest further
      structural modifications to access to more potent BACE-1 inhibitors.

PMID- 16412633
TI  - Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics,
      pharmacodynamics, and efficacy in an arterial baboon thrombosis model.
AB  - Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex
      inhibitors were generated through structure-based design. The pharmacokinetic
      properties of an optimized analog (9) were characterized in several preclinical
      species, demonstrating pharmacokinetic characteristics suitable for once-a-day
      dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose
      dependent manner after intravenous administration in a baboon thrombosis model,
      and a pharmacodynamic concentration-response model was developed to describe the
      platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the
      baboon model are also presented.

PMID- 16412634
TI  - Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2:
      Optimization of P1 and N-aryl.
AB  - A systematic study of anilines led to the discovery of a metabolically robust
      fluoroindoline replacement for the alkoxy aniline toxicophore in 1.
      Investigations of the P1 pocket resulted in the discovery of a wide tolerance of
      functionality leading to the discovery of 11 as a potent and selective inhibitor
      of cathepsin S.

PMID- 16412635
TI  - A novel series of urea-based peptidomimetic calpain inhibitors.
AB  - A series of peptide aldehyde derivatives in which the P(2) chiral carbon has been
      replaced with nitrogen were synthesized as urea-based peptidomimetic inhibitors
      of mu-calpain. The compounds mirrored the general SAR of peptidyl aldehyde
      calpain inhibitors but displayed greater selectivity for mu-calpain over
      cathepsin B.

PMID- 16412636
TI  - Tricyclic azepine derivatives: pyrimido[4,5-b]-1,4-benzoxazepines as a novel
      class of epidermal growth factor receptor kinase inhibitors.
AB  - A novel class of pyrimido[4,5-b]-1,4-benzoxazepines is described as inhibitors of
      epidermal growth factor receptor (EGFR) tyrosine kinase. Two compounds display
      potent EGFR inhibitory activity of less than 1 microM in cellular phosphorylation
      assays (IC(50) 0.47-0.69 microM) and are highly selective against a small kinase
      panel. Such compounds demonstrate anti-EGFR activity within a class that is
      different from any known EGFR inhibitor scaffolds. They also provide a basis for
      the design of kinase inhibitors with the desired selectivity profile.

PMID- 16412637
TI  - Synthesis and analgesic activity of secondary amine analogues of
      pyridylmethylamine and positional isomeric analogues of ABT-594.
AB  - A series of highly sterically hindered secondary amine analogues of
      pyridylmethylamine (7a-f, 8a-c) and positional isomeric analogues of ABT-594 (9a
      c) were synthesized and evaluated for their in vivo analgesic activity. The
      compounds 7a and 7d show potent analgesic activity and lower toxicity. Some
      interesting structure-activity relationships have been revealed.

PMID- 16412638
TI  - 6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists.
AB  - A series of 6H-benzo[c]chromen-6-one and 6H-benzo[c]chromene derivatives were
      prepared, and the affinity and selectivity for ERalpha and ERbeta was measured.
      Many of the analogs were found to be potent and selective ERbeta agonists. Bis
      hydroxyl at positions 3 and 8 is essential for activity in a HTRF coactivator
      recruitment assay. Additional modifications at both phenyl rings led to compounds
      with ERbeta<10nM potency and >100-fold selectivity over ERalpha.

PMID- 16412639
TI  - Centromere formation: from epigenetics to self-assembly.
AB  - This review is part of the Chromosome segregation and Aneuploidy series that
      focuses on the importance of chromosome segregation mechanisms in maintaining
      genome stability. Centromeres are specialized chromosomal domains that serve as
      the foundation for the mitotic kinetochore, the interaction site between the
      chromosome and the mitotic spindle. The chromatin of centromeres is distinguished
      from other chromosomal loci by the unique incorporation of the centromeric
      histone H3 variant, centromere protein A. Here, we review the genetic and
      epigenetic factors that control the formation and maintenance of centromeric
      chromatin and propose a chromatin self-assembly model for organizing the higher
      order structure of the centromere.

PMID- 16412640
TI  - A method for comparing manual muscle strength measurements with joint moments
      during walking.
AB  - This paper describes a protocol for dynamometer assisted manual muscle testing of
      the major muscle groups of the lower extremity and its application to 11 able
      bodied children who also had conventional gait analysis to obtain joint kinetics.
      Data from the manual muscle testing was processed in such a way that the results
      for maximum muscle strength (grade 5) and resistance against gravity alone (grade
      3) were presented in Nm/kg allowing direct comparison with conventional joint
      kinetics. The strength measurements of the hip muscles and the knee extensors
      were between two and three times the moments exerted during normal walking. Those
      of the knee flexors and dorsiflexors were about five times the joint moments.
      Measured plantarflexor strength was only just greater than the moment exerted
      during walking. These results, particularly those for the plantarflexors,
      question how valid it is to use measures of isometric muscle strength as
      indicators of muscle function during activity. The study also compares grade 3
      muscle strength with both grade 5 strength and the maximum joint moments. For all
      muscle groups tested grade 3 muscle strength was less than the maximum moment
      exerted during normal walking. For the plantarflexors it was less than 1% of that
      moment. The study demonstrates that reliable isometric muscle testing is possible
      in able-bodied children but requires considerable care and is time consuming.
      More work is required to understand how measurements made in this way relate to
      how muscles function during activity.

PMID- 16412641
TI  - Neuromuscular mechanisms and anthropometric modifications in the initial stages
      of independent gait.
AB  - The gait acquisition is an important milestone of motor development. Structural
      modifications observed during this period add complexity to the process, and the
      child needs to use appropriate neuromuscular strategies to walk independently.
      The objective of this study was to document the longitudinal modifications in
      neuromuscular mechanisms and in functional anthropometric measures during
      independent gait acquisition in typically developing children. Twelve children
      were followed for 2 months after gait acquisition, with its initial period
      documented by the standardized test Alberta Infant Motor Scale. Quantification of
      the EMG signals of six muscles in the right lower limb allowed the calculation of
      the co-contraction indexes (CCI) considering pairs of antagonistic muscles,
      representing the hip, knee and ankle joints. The CCIs were summed up to yield a
      total index. Anthropometric measures were transformed into gravitational torque
      (mLg) values for stance and swing phases of gait. Statistical analyses included
      repeated measures ANOVA models with one factor (week post-acquisition) for the
      dependent variables mLg and normalized CCI (CCI/mLg). A significant increase was
      observed in the mLg during the period evaluated both in stance and swing phases
      (p=0.0001). In addition, there was a decrease in the value of the normalized hip
      and total CCIs in both phases of gait (p<0.05). The results revealed changes in
      the neuromuscular mechanisms used by typical children to deal with the demands
      involved in the process of gait acquisition.

PMID- 16412642
TI  - Recovery responses to surrogate slipping tasks differ from responses to actual
      slips.
AB  - Slipping and slip-related falls are a common and potentially dangerous problem,
      especially for older adults. We believe that it is possible to train compensatory
      stepping responses of older adults to reduce the incidence of slip-related falls.
      However, such an approach requires further understanding of the causal
      biomechanical distinctions between a successful and an unsuccessful recovery
      effort. Surrogate tasks are often used to study complex biomechanical events
      associated with large postural disturbances. Although surrogate tasks enhance
      experimental control over one or more elements of a generally more complex event,
      such control may change the task of interest by imposing biomechanical
      constraints that reduce the validity of the surrogate. The purpose of the present
      study was to quantify the differences in lower extremity and trunk kinematics
      following a simulated slip versus an actual slip. We hypothesized that the
      simulated slips would be less variable than real slips and would result in
      significantly different, and less realistic recovery kinematics. Twenty-two
      healthy young adults were subjected to unexpected slips using a custom slipping
      platform and artificial ice. Biomechanical variables associated with the slipping
      foot were significantly less variable in those slips induced with the platform
      compared to slips induced with the artificial ice. Significant differences
      between successful and unsuccessful recovery efforts were found for lower
      extremity and trunk kinematics on both types of slipping surface. Notably, 40% of
      the variables for which between surface differences were significant were also
      those variables that distinguished successful and unsuccessful recovery efforts
      on the two surfaces. The results suggest that slips induced using artificial ice
      more accurately reflect the type of slips that occur in the community.

PMID- 16412643
TI  - The reaction of artemisinins with hemoglobin: a unified picture.
AB  - The reactions with hemoglobin of artemisinin and of its parent compounds, sodium
      artesunate and dihydroartemisinin, were investigated by visible absorption
      spectroscopy under standard solution conditions (50 mM phosphate buffer, pH 7, 37
      degrees C). Notably, these antimalarial drugs were found to react with hemoglobin
      (i.e., ferrous heme), but not with methemoglobin (i.e., ferric heme). The
      reaction selectively occurs at the heme sites and consists of the progressive,
      slow decay of the Soret band, as a consequence of heme alkylation and subsequent
      loss of pi electron delocalization. For the various tested compounds the process
      reaches completion within approximately 30-70 h. Additional experiments were
      carried out upon adopting the solution conditions described by Meunier et al. and
      by Kannan et al. in their recent studies. Some reactivity of artemisinin with
      methemoglobin was indeed detected after addition of 50% v/v acetonitrile, most
      likely as a consequence of extensive protein unfolding. A unified description for
      the reactions of artemisinins with hemoglobin is given.

PMID- 16412644
TI  - Novel cyano- and amidino-substituted derivatives of thieno[2,3-b]- and thieno[3,2
      b]thiophene-2-carboxanilides and thieno[3',2':4,5]thieno- and
      thieno[2',3':4,5]thieno [2,3-c]quinolones: synthesis, photochemical synthesis,
      DNA binding, and antitumor evaluation.
AB  - A series of cyano- and amidino-substituted derivatives of thieno[2,3-b]- and
      thieno[3,2-b]thiophene-2-carboxanilides and their 'cyclic' derivatives
      (quinolones) were synthesized. 'Cyclic' compounds displayed a rather strong and
      differential antiproliferative effect on various cell lines, while the 'acyclic'
      amidino-substituted compounds were much more active, but showing mostly non
      differential cytotoxicity, whereas cyano-substituted compounds (2a,b) produced a
      strikingly strong effect selectively on HeLa and Hep-2 cell lines.
      Antiproliferative activity of 'cyclic' derivatives is very likely caused by
      intercalation into DNA, while their 'acyclic' analogues use other target(s)
      and/or mechanisms of action.

PMID- 16412645
TI  - Design, synthesis, and anti-integrase activity of catechol-DKA hybrids.
AB  - Following the discovery of diketoacid-containing compounds as HIV-1 integrase
      (IN) inhibitors, a plethora of new molecules have been published leading to four
      drugs under clinical trial. In an attempt to rationally design new dimeric
      diketoacids (DKAs) targeting two divalent metal ions on the active site of IN,
      potent inhibitors against purified IN were found with varied selectivity for
      strand transfer. In this context, we designed and synthesized a new series of
      catechol-DKA hybrids. These compounds presented micromolar anti-integrase
      activities with moderate antiviral properties.

PMID- 16412646
TI  - Synthesis, in vitro and in vivo antimycobacterial activities of diclofenac acid
      hydrazones and amides.
AB  - Various diclofenac acid hydrazones and amides were synthesized and evaluated for
      in vitro and in vivo antimycobacterial activities against Mycobacterium
      tuberculosis. Preliminary results indicated that most of the compounds
      demonstrated better in vitro antimycobacterial activity (MIC: 0.0383-7.53 microM)
      than diclofenac (MIC: 21.10 microM) and ciprofloxacin (MIC: 9.41 microM). Among
      the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy-7-[[N4-(2-(2-(2,6
      dichlorophenylamino)phenyl)acetyl)-3-methyl]-N1-piperazinyl]-4-oxo-1,4-dihydro-3
      quinoline carboxylic acid (5d) was found to be the most active compound in vitro
      with MIC of 0.0383 microM and was more potent than first line antitubercular drug
      isoniazid (MIC: 0.1822 microM). In the in vivo animal model 5d decreased the
      bacterial load in lung and spleen tissues with 2.42- and 3.66-log10 protections,
      respectively, at 25 mg/kg body weight.

PMID- 16412647
TI  - Synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2
      phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives.
AB  - The present report describes the synthesis and antiproliferative evaluation of
      certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2
      phenylquinoline derivatives. The antiproliferative activity of 4'-COMe
      substituted derivatives decreased in an order of 6-OMe (1, 3.89 microM) > 8-OMe
      (8, 10.47 microM) > 8-OH (9, 14.45 microM), indicating that the position of
      substitution at the quinoline ring is crucial. For 3'-COMe derivatives, the
      antiproliferative activity of 8-OH (11, 1.20 microM) is more potent than its 8
      OMe counterpart (10, 8.91 microM), indicating that a H-bonding donating
      substituent is more favorable than that of a H-bonding accepting group.
      Comparison of 8-OH derivatives, the antiproliferative effect of COMe (11) is more
      potent than its oxime derivative (15a, 2.88 microM), which in turn is more potent
      than the methyloxime counterpart (15b, 5.50 microM). Compound 11 is especially
      active against the growth of certain solid cancer cells such as HCT-116 (colon
      cancer), MCF7, and MDA-MB-435 (breast cancer) with GI50 values of 0.07, <0.01,
      and <0.01 microM, respectively. Flow cytometric analyses revealed that growth
      inhibition by 11 and 15a was due to accumulation in S-phase. This result is
      interesting because 2-phenylquinolone derivatives have been reported to be
      antimitotic agents which induced cell cycle arrest in G2/M phase.

PMID- 16412648
TI  - Natural products as starting materials for development of second-generation SERCA
      inhibitors targeted towards prostate cancer cells.
AB  - An analysis of the binding of the 8-O-N-tert-butoxycarbonyl-12-aminododecanoyl
      derivative of 8-O-debutanoylthapsigargin to the target molecule, the SERCA pump,
      has revealed the importance of the length and flexibility of the side chain
      attached to O-8. Based on the analysis a series of analogues to the 2
      unsubstituted analogue trilobolide has been constructed and shown to be
      equipotent with thapsigargin as SERCA inhibitors. Only the 12-Boc
      aminododecaonoyl derivative, however, was found to be apoptotic.

PMID- 16412650
TI  - Antitumor activity of some natural flavonoids and synthetic derivatives on
      various human and murine cancer cell lines.
AB  - The effect of various natural flavonoids, cinnamic acid derivatives, and a series
      of synthetic flavones on cell proliferation was evaluated in vitro in a panel of
      established human and murine tumor cell lines. The most potent antiproliferative
      agents were caffeic acid n-butyl ester (12) > 2'-nitroflavone (26) > caffeic acid
      ethyl ester (11) approximately = 2',6-dinitroflavone (27) > apigenin (3) > 3'
      bromoflavone (20) approximately = 2'-fluoro-6-bromoflavone (31). Some compounds
      showed a moderate effect, the order of cytotoxic activities being chrysin (2) >
      2'-fluoro-6-chloroflavone (30) approximately = 2'-chlorochrysin (32) > alpha
      naphthoflavone (7) > beta-naphthoflavone (8) approximately = 6-chloroflavone (14)
      approximately = 6-bromoflavone (15) approximately = 4'-nitroflavone (23). A
      structure-activity relationship analysis of each group of compounds was
      performed. None of the natural or synthetic compounds tested affected the
      proliferation of epithelial cells derived from normal mammary gland of mice or
      fibroblastic cells from mouse embryo, suggesting a selective action against tumor
      cells.

PMID- 16412649
TI  - Binding analysis of glycyrrhetinic acid to human serum albumin: fluorescence
      spectroscopy, FTIR, and molecular modeling.
AB  - Fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), and
      molecular modeling methods were employed to analyze the binding of glycyrrhetinic
      acid (GEA) to human serum albumin (HSA) under physiological conditions with GEA
      concentrations from 4.0x10(-6) to 4.5x10(-5) mol L(-1). The binding of GEA to HSA
      was via two types of sites: the numbers of binding site for the first type was
      near 0.45 and for the second type it was approximately 0.75. The binding
      constants of the second type binding site were lower than those of the first type
      binding site at corresponding temperatures, the results suggesting that the first
      type of binding site had high affinity and the second binding site involved other
      sites with lower binding affinity and selectivity. The fluorescence titration
      results indicated that GEA quenched the fluorescence intensity of HSA through
      static mechanism. The FTIR spectra evidence showed that the protein secondary
      structure changed with reduction of alpha-helices about 26.2% at the drug to
      protein molar ratio of 3. Thermodynamic analysis showed that hydrogen bonds were
      the mainly binding force in the first type of binding site, and hydrophobic
      interactions might play a main role in the second type of binding site.
      Furthermore, the study of computational modeling indicated that GEA could bind to
      the site I of HSA and hydrophobic interaction was the major acting force for the
      second type of binding site, which was in agreement with the thermodynamic
      analysis.

PMID- 16412651
TI  - Quantitative structure-activity relationship of spirosuccinimide type aldose
      reductase inhibitors diminishing sorbitol accumulation in vivo.
AB  - Racemate physicochemical descriptors are employed to probe the quantitative
      structure-activity relationship of spirosuccinimide type aldose reductase
      inhibitors and the in vivo inhibitory activity of sorbitol accumulation. The in
      vivo activity data include the percent inhibition and ED50 assay results on the
      literature. The derived QSAR equations show that the hydrophobic character of
      aldose reductase inhibitor is the major contributing factor to enhance in vivo
      activity. As the hydrophobicity of compounds is related to both the membrane
      permeability and the binding affinity to the aldose reductase, its contribution
      to the pharmacokinetic behavior is further scrutinized by evaluating pKa and the
      Caco-2 cell permeability. The high correlation between ED50 and the Caco-2 cell
      permeability of in vitro active compounds indicates that the membrane
      permeability is essential for in vivo efficacy.

PMID- 16412652
TI  - 6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones: reversed lactam analogues
      of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity.
AB  - 6-Substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6]naphthyridin-5
      ones were synthesized and evaluated for topoisomerase I-targeting activity and
      cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited
      exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast
      to topotecan, no resistance was observed with several of these reversed lactam
      analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or
      BCRP.

PMID- 16412654
TI  - Synthesis and antimicrobial activity of new (4,4,4-trihalo-3-oxo-but-1-enyl)
      carbamic acid ethyl esters, (4,4,4-trihalo-3-hydroxy-butyl)-carbamic acid ethyl
      esters, and 2-oxo-6-trihalomethyl-[1,3]oxazinane-3-carboxylic acid ethyl esters.
AB  - This work presents a three-step synthesis of a new series of 4-substituted 2-oxo
      6-trihalomethyl-[1,3]oxazinane-3-carboxylic acid ethyl esters, from beta
      alkoxyvinyl trihalomethyl ketones of general formula X3C-C(O)-CH=C(R)-OR(1),
      where R = H, Me, Ph, and 4-Me-Ph; R(1) = Me and Et; and X = F and Cl. The Michael
      addition-substitution of the ethyl carbamate on beta-alkoxyvinyl trihalomethyl
      ketones furnished the corresponding (4,4,4-trihalo-3-oxo-but-1-enyl)-carbamic
      acid ethyl esters. These compounds underwent reduction with NaBH4 leading to the
      respective (4,4,4-trihalo-3-hydroxy-butyl)-carbamic acid ethyl esters. The 3
      hydroxy-butyl carbamates were submitted to cyclization reaction with triphosgene
      to give a series of 4-substituted 2-oxo-6-trihalomethyl-[1,3]oxazinane-3
      carboxylic acid ethyl esters. The in vitro antimicrobial activity, of some of the
      three new series of the title compounds, was assessed against a panel of
      microorganisms including yeast like fungi, bacteria, and algae, and their minimal
      inhibitory concentration and minimal fungicidal, bactericidal, and algacidal
      concentrations were determined. Some of the analyzed carbamates exhibited
      significant in vitro antimicrobial activity.

PMID- 16412653
TI  - Synthesis and preliminary chemotherapeutic evaluation of the fully C-linked
      glucuronide of N-(4-hydroxyphenyl)retinamide.
AB  - All-trans retinoic acid analogues such as N-(4-hydroxyphenyl)retinamide (4-HPR)
      are effective chemopreventive and chemotherapeutic agents but their utility has
      been hampered by dose-limiting side effects. The glucuronide derivatives of 4
      HPR, the oxygen-linked 4-HPROG and the carbon-linked 4-HPRCG, have been found to
      be more effective agents. The synthetic route to the fully C-linked analogue of 4
      HPROG (4-HBRCG), which employs Suzuki coupling and Umpolung chemistries as key
      methodologies, is shown. The results of this study show 4-HBRCG to be an
      effective chemotherapeutic agent in a rat mammary tumor model while being devoid
      of classical retinoid toxicities.

PMID- 16412655
TI  - Site-specific recombination of asymmetric lox sites mediated by a
      heterotetrameric Cre recombinase complex.
AB  - Previous reports have demonstrated that new Cre recombinase specificities can be
      developed for symmetrically designed lox mutants through directed evolution. The
      development of Cre variants that allow the recombination of true asymmetric lox
      mutant sites has not yet been addressed, however. In the present study, we
      demonstrate that a mixture of two different site-specific Cre recombinase
      molecules (wt Cre and a mutant Cre) catalyzes efficient recombination between two
      asymmetric lox sites in vitro, presumably via formation of a functionally active
      heterotetrameric complex. The results may broaden the application of site
      specific recombination in basic and applied research, including the custom-design
      of recombinases for natural, asymmetric, and lox-related target sequences present
      in the genome. Future applications may potentially include genomic manipulations,
      for example, site-specific integrations, deletions or substitutions within
      precise regions of the genomes of mammalians and other organisms.

PMID- 16412656
TI  - A novel naturally occurring tripyrrole with potential nuclease and anti-tumour
      properties.
AB  - The DNA targeting and membrane damaging activities of a novel tripyrrole 1
      obtained as a red pigment from the Micrococcus sp. were investigated. It was
      found that compound 1 binds with DNA efficiently and facilitates copper-mediated
      DNA cleavage as well as peroxidation of membrane lipids by a process that does
      not require any external reducing agent. Compound 1 also showed impressive
      cytotoxicity to both mouse and human tumour cell lines. The membrane damaging
      ability of compound 1 might be vital in its nuclease and cytotoxicity properties.
      Interestingly, compared to the various DNA cleaving agents, compound 1 showed a
      preferential binding with the G-C rich domain.

PMID- 16412657
TI  - Determination of the Pu240/Pu239 ratio by alpha spectrometry using the WinALPHA
      program.
AB  - The isotopic ratio of 240Pu to 239Pu is an important parameter in identifying the
      origin of plutonium in a given radioactive sample. High-resolution mass
      spectrometry is generally accepted as an accurate technique for determining this
      ratio, but this is a very costly method. Alternatives to this method are alpha-
      and gamma-spectrometry studies but the problem with these low-cost method lies
      with the analysis of the spectrum. Recently, Noy et al. [2004. Nucl. Instrum.
      Methods in Phys. Res. A 525, 522-528] developed a computer program code called
      WinALPHA to quantitatively analyze the alpha spectrum; the program is available
      from the IAEA website. In this paper, we report the results obtained from the
      analysis of the alpha spectrum of plutonium from power bearing product samples
      from power reactor fuel reprocessing plant using the WinALPHA program. The
      results are found to be in good agreement (within 1-2%) with results from mass
      spectrometry.

PMID- 16412659
TI  - Gastric cancer: standards for the 21st century.
AB  - Although the incidence of gastric cancer has been decreasing in the United
      States, it remains a leading cause of cancer death in the world, only lung cancer
      causes more deaths worldwide. The combination of relatively low prevalence, lack
      of pathognomonic symptoms, and lack of defined risk factors are associated with a
      delay in diagnosis leading to a dismal prognosis. For localized disease, surgery
      remains a cornerstone of treatment but much controversy remains regarding optimal
      peri-operative therapy. For advanced disease, several new agents and new
      combination chemotherapies have offered encouraging results. This paper seeks to
      review the major topics surrounding gastric cancer and cover the results of
      recently reported and ongoing trials.

PMID- 16412658
TI  - Visual deficits in a mouse model of Batten disease are the result of optic nerve
      degeneration and loss of dorsal lateral geniculate thalamic neurons.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessive disorder
      of childhood caused by mutations in CLN3. Although visual deterioration is
      typically the first clinical sign to manifest in affected children, loss of Cln3
      in a mouse model of JNCL does not recapitulate this retinal deterioration. This
      suggests that either the loss of CLN3 does not directly affect retinal cell
      survival or that nuclei involved in visual processing are affected prior to
      retinal degeneration. Having previously demonstrated that Cln3(-/-) mice have
      decreased optic nerve axonal density, we now demonstrate a decrease in nerve
      conduction. Examination of retino-recipient regions revealed a decreased number
      of neurons within the dorsal lateral geniculate nucleus (LGNd). We demonstrate
      decreased transport of amino acids from the retina to the LGN, suggesting an
      impediment in communication between the retina and projection nuclei. This study
      defines a novel path of degeneration within the LGNd, providing a mechanism for
      causation of JNCL visual deficits.

PMID- 16412660
TI  - Effect of tempol on altered angiotensin II and acetylcholine-mediated vascular
      responses in thoracic aorta isolated from rats with insulin resistance.
AB  - The altered vascular responses to various vasopressors and relaxants have been
      well reported in various animal models of hypertension, insulin resistance and
      diabetes. Though the role of oxidative stress (increased superoxide levels)
      associated with these altered vascular responses in hyperglycemic/diabetic state
      is well documented, the role of the same remains to be largely unknown in
      vascular dysfunction coupled with prediabetic insulin resistant state. The
      objective of the present study was therefore to elucidate the role of free
      radicals particularly superoxides if any associated with vascular dysfunction in
      diet-induced insulin resistance of rats. In this regard, the effect of tempol (a
      membrane permeable superoxide dismutase mimetic/free radical scavenger) on the
      enhanced Ang II-induced contraction and impaired-ACh mediated relaxation in
      thoracic aorta of rats with insulin resistance was studied. Ang II-induced
      contraction and ACh-mediated relaxation responses were recorded isometrically in
      endothelium intact and denuded thoracic aortic ring preparations isolated from
      male Sprague-Dawley rats which were fed with either normal pellet diet (NPD)
      (control group) or high fat diet (HFD) (insulin resistant group) for 4 weeks. The
      HFD-fed rats exhibited characteristic features of insulin resistance syndrome
      viz., obesity, hyperinsulinaemia, mild hyperglycemia, hypertriglyceridemia,
      hypercholesterolemia, glucose intolerance and hypertension. Maximal contractile
      response (E(max)) to Ang II was increased in endothelium intact aortic ring
      preparations obtained from HFD-fed rats as compared to NPD-fed control rats.
      Denudation of endothelium significantly increased Ang II-mediated E(max)
      responses in thoracic aortic rings of NPD-fed rats, whereas it produced only
      minimal alteration to the E(max) in the HFD-fed rats. In addition, ACh-mediated
      relaxation response was impaired in endothelium intact aortic rings isolated from
      HFD-fed rats. Tempol (30-300 microM) significantly and dose dependently inhibited
      enhanced vascular responses (E(max)) of Ang II in endothelium intact, but not in
      endothelium denuded aortic ring preparations. Tempol (30 microM) reversed the
      impaired acetylcholine (ACh)-mediated relaxations in endothelium intact aortic
      ring preparations of HFD-fed rats. Endothelium independent vasorelaxations (EIV)
      to sodium nitroprusside (SNP) were similar for both NPD and HFD. In conclusion,
      our results indicate that superoxide radicals play crucial role in enhanced
      contractile and impaired vasodilatory responses to Ang II and ACh, respectively,
      in thoracic aortic rings isolated from diet-induced insulin resistant rats.

PMID- 16412661
TI  - Dual mechanism of mangiferin protection against iron-induced damage to 2
      deoxyribose and ascorbate oxidation.
AB  - We studied mangiferin effects on the degradation of 2-deoxyribose induced by
      Fe(III)-EDTA/citrate plus ascorbate, in relation to ascorbate oxidation (measured
      at 265 nm). Results revealed that mangiferin was equally effective in preventing
      degradation of both 15 and 1.5 mM 2-deoxyribose. At a fixed Fe(III)
      concentration, increasing the concentration of ligands (either EDTA or citrate)
      caused a significant reduction in the protective effects of mangiferin.
      Interestingly, mangiferin strongly stimulated Fe(III)-EDTA ascorbate oxidation,
      but inhibited it when citrate was used as iron co-chelator. Mangiferin stimulated
      O2 consumption due to Fe(II) (formed by Fe(III) ascorbate reduction) autoxidation
      when the metal ligand was EDTA, but inhibited it when citrate was used. These
      results suggest that mangiferin removes iron from citrate, but not from EDTA,
      forming an iron-mangiferin complex that cannot induce ascorbate oxidation
      effectively, thus inhibiting iron-mediated oxyradical formation. Taken together,
      these results indicate that mangiferin works mainly by a mechanism different from
      the classical hydroxyl radical scavengers, keeping iron in its ferric form, by
      complexing Fe(III), or stimulating Fe(II) autoxidation.

PMID- 16412662
TI  - O6-(4-bromothenyl)guanine (PaTrin-2), a novel inhibitor of O6-alkylguanine DNA
      alkyl-transferase, increases the inhibitory activity of temozolomide against
      human acute leukaemia cells in vitro.
AB  - Anti-tumour activity of triazene compounds of clinical interest [i.e. dacarbazine
      and temozolomide (TMZ)] relies mainly on the generation of methyl adducts to
      purine bases of DNA. Two DNA repair enzyme systems, i.e. the O6-guanine-alkyl
      transferase (MGMT) and mismatch repair (MMR), play a predominant role in
      conditioning the cytotoxic effects of triazenes. In particular, high levels of
      MGMT associated with target cells are responsible of resistance to triazenes. On
      the contrary, the presence of MMR is required for the cytotoxic effects of these
      compounds. Previous studies performed by our group and a more recent clinical
      investigation reported by Karen Seiter, pointed out that triazene compounds could
      play an important role in the treatment of refractory acute leukaemia. Leukaemia
      blasts, especially of lymphoblastic leukaemia, show frequently high levels of
      MGMT activity. Therefore, it reasonable to hypothesize that combined treatment of
      leukaemia patients with triazene compounds along with MGMT inhibitors could lead
      to a better control of the disease. PaTrin-2 (O6-(4-bromothenyl)guanine, PAT) is
      a potent and scarcely toxic MGMT inhibitor recently introduced in clinical
      trials. This drug is used in combination with triazene compounds in order to
      augment their anti-tumour efficacy against neoplastic cells endowed with high
      MGMT activity. The present report describes, for the first time, pre-clinical in
      vitro studies on the cytotoxic activity of combined treatment with PAT+TMZ
      against long-term cultured leukaemia cells and primary leukaemia blasts obtained
      from patients with acute lymphoblastic leukaemia or acute myeloblastic leukaemia.
      The results point out that, both in long-term cultured leukaemia cell lines and
      in primary blast samples, PAT could improve dramatically the sensitivity of
      malignant cells to the cytotoxic effects of TMZ. This sensitizing effect is
      detectable when leukaemia cells show resistance mechanisms based on a MGMT
      proficient phenotype. On the contrary, when resistance to TMZ is dependent on MMR
      deficiency, no influence of PAT can be detected in various experimental
      conditions. In conclusion, these results appear to provide disease-oriented
      rational basis to design novel clinical protocols for the treatment of acute
      leukaemia with combined administration of PAT and triazene compounds.

PMID- 16412663
TI  - Ginkgo biloba extract protects against ionizing radiation-induced oxidative organ
      damage in rats.
AB  - The present study was designed to determine the possible protective effects of
      Ginkgo biloba extract (EGb) against oxidative organ damage induced by irradiation
      (IR). Sprague-Dawley rats were exposed to whole-body IR (800 cGy) after a 15-day
      pretreatment with either saline or EGb (50 mg/kg/day), intraperitoneally, and
      treatments were repeated immediately after the IR. Then the rats were decapitated
      at either 6 h or 72 h after IR, where EGb or saline injections were repeated once
      daily. Lung, liver, kidney and ileum samples were obtained for the determination
      of malondialdehyde, glutathione levels, myeloperoxidase activity and collagen
      contents, while oxidant-induced DNA fragmentation was evaluated in the ileal
      tissues. All tissues were also examined microscopically and assayed for the
      production of reactive oxidants using chemiluminescence (CL). Lactate
      dehydrogenase (LDH)-an indicator of tissue damage and TNF-alpha were assayed in
      serum samples. In the saline-treated irradiation groups, glutathione levels were
      decreased significantly, while the malondialdehyde levels, myeloperoxidase
      activity and collagen content were increased in the tissues (p < 0.01-0.001),
      which were in parallel with the increases in luminol and lucigenin CL values. In
      the EGb treated-IR groups, all of these oxidant responses were prevented
      significantly (p < 0.05-0.01). LDH and TNF-alpha levels, which were increased
      significantly (p < 0.01-0.001) following IR, were decreased (p < 0.05-0.001) with
      EGb treatment. In conclusion, the present data demonstrate that EGb, through its
      free radical scavenging and antioxidant properties, attenuates irradiation
      induced oxidative organ injury, suggesting that EGb may have a potential benefit
      in enhancing the success of radiotherapy.

PMID- 16412664
TI  - Analysis of native milk oligosaccharides directly from thin-layer chromatography
      plates by matrix-assisted laser desorption/ionization orthogonal-time-of-flight
      mass spectrometry with a glycerol matrix.
AB  - We have recently presented a new method for direct coupling of high-performance
      thin-layer chromatography (HPTLC) with matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS), illustrated by the analysis
      of a complex ganglioside mixture. In the current communication, an adaptation of
      this procedure to mixtures of native oligosaccharides from human and from
      elephant milk is described. The key features in this method are (1) glycerol as a
      liquid matrix, to provide a homogeneous wetting of the silica gel and a simple
      and fast MALDI preparation protocol, (2) an infrared (IR) laser for volume
      material ablation and particular soft desorption/ionization conditions, and (3)
      an orthogonal time-of-flight mass spectrometer for a high mass accuracy,
      independent of any irregularity of the silica gel surface. Chromatographic
      "mobility profiles" were determined by scanning the laser beam across the analyte
      bands. The current limit of detection for the MS analysis was determined to
      approximately 10 pmol of individual oligosaccharides spotted for chromatography.
      A liquid composite matrix, containing glycerol and the ultraviolet (UV-)MALDI
      matrix alpha-cyano-4-hydroxycinnamic acid, allows a direct HPTLC-MALDI-MS
      analysis with a 337 nm-UV laser as well. Compared to the IR-MALDI mode, the
      analytical sensitivity in UV-MALDI was found to be lower by one order of
      magnitude, whereas unspecific analyte ion fragmentation as well as adduct
      formation was found to be more extensive.

PMID- 16412665
TI  - Analysis of speech-related variance in rapid event-related fMRI using a time
      aware acquisition system.
AB  - Speech production introduces signal changes in fMRI data that can mimic or mask
      the task-induced BOLD response. Rapid event-related designs with variable ISIs
      address these concerns by minimizing the correlation of task and speech-related
      signal changes without sacrificing efficiency; however, the increase in residual
      variance due to speech still decreases statistical power and must be explicitly
      addressed primarily through post-processing techniques. We investigated the
      timing, magnitude, and location of speech-related variance in an overt picture
      naming fMRI study with a rapid event-related design, using a data acquisition
      system that time-stamped image acquisitions, speech, and a pneumatic belt signal
      on the same clock. Using a spectral subtraction algorithm to remove scanner
      gradient noise from recorded speech, we related the timing of speech, stimulus
      presentation, chest wall movement, and image acquisition. We explored the
      relationship of an extended speech event time course and respiration on signal
      variance by performing a series of voxelwise regression analyses. Our results
      demonstrate that these effects are spatially heterogeneous, but their anatomic
      locations converge across subjects. Affected locations included basal areas
      (orbitofrontal, mesial temporal, brainstem), areas adjacent to CSF spaces, and
      lateral frontal areas. If left unmodeled, speech-related variance can result in
      regional detection bias that affects some areas critically implicated in language
      function. The results establish the feasibility of detecting and mitigating
      speech-related variance in rapid event-related fMRI experiments with single word
      utterances. They further demonstrate the utility of precise timing information
      about speech and respiration for this purpose.

PMID- 16412666
TI  - A non-parametric approach for co-analysis of multi-modal brain imaging data:
      application to Alzheimer's disease.
AB  - We developed a new flexible approach for a co-analysis of multi-modal brain
      imaging data using a non-parametric framework. In this approach, results from
      separate analyses on different modalities are combined using a combining function
      and assessed with a permutation test. This approach identifies several cross
      modality relationships, such as concordance and dissociation, without explicitly
      modeling the correlation between modalities. We applied our approach to
      structural and perfusion MRI data from an Alzheimer's disease (AD) study. Our
      approach identified areas of concordance, where both gray matter (GM) density and
      perfusion decreased together, and areas of dissociation, where GM density and
      perfusion did not decrease together. In conclusion, these results demonstrate the
      utility of this new non-parametric method to quantitatively assess the
      relationships between multiple modalities.

PMID- 16412667
TI  - Intracerebral dynamics of saccade generation in the human frontal eye field and
      supplementary eye field.
AB  - Recent functional imaging and electrical stimulation studies have localized in
      humans two frontal regions critical for the production of saccadic and anti
      saccadic eye movements: the frontal and supplementary eye fields (FEF and SEF,
      respectively). We investigated the time course of their activations during the
      generation of pro- and anti-saccades from direct intracranial EEG recordings of
      three human epileptic patients. We found the preparation and the production of
      the saccades to be coincident with focal and transient increases of EEG power
      above 60 Hz. Those were produced in very specific brain sites distributed in the
      FEF and the SEF (as identified by previous human studies at a coarser time
      resolution). Furthermore, the spatio-temporal resolution of those recordings
      turned out to be sufficient to discriminate anatomically between several types of
      neural responses, determined either by the visual or by the motor components of
      the saccade tasks, and within this second category of responses, between some
      associated with the preparation of the saccades and others associated with their
      execution. Altogether, this study provides the first evidence of high-frequency
      neural responses in the generation of saccades in humans, and provides a firm
      basis for other studies detailing further the functional organization of the
      human oculomotor system at this level of spatial and temporal resolution.

PMID- 16412669
TI  - Expression of neuronal nitric oxide synthase variant, nNOS-mu, in rat brain.
AB  - Neuronal nitric oxide synthase (nNOS) is alternatively spliced. An nNOS splice
      variant form, nNOS-mu, was first found to be selectively expressed in rat
      skeletal muscle and heart. To date, the expression of nNOS-mu in the brain has
      not been well characterized. The aim of this study was to determine whether nNOS
      mu is expressed in rat brain, and whether nNOS-mu exhibits a specific expression
      pattern. To analyze the expression of nNOS-mu, we generated a monoclonal antibody
      that is specific for nNOS-mu. An immunoblot analysis using this antibody showed
      that nNOS-mu is expressed in the rat brain at a measurable level, which was 10.3%
      of total nNOSs. In rat brain, the nNOS-mu expression was high in the
      mesencephalon and the cerebellum. nNOS-mu was immunohistochemically localized in
      neurites and perikarya of large neurons. In the cerebellum, granule cells showed
      marked staining, while weak staining was detected in basket and stellate cells.
      This expression pattern is different from that described for nNOS and suggests
      that nNOS-mu plays unique roles in different neurons.

PMID- 16412670
TI  - NADPH analog binding to constitutive nitric oxide activates electron transfer and
      NO synthesis.
AB  - We report here that NADPH analogs such as 2'5'ADP, ATP, and 2'AMP paradoxically
      activate constitutive calcium/calmodulin regulated nitric oxide synthases (cNOS),
      including the endothelial isoform (eNOS) and the neuronal isoform (nNOS). These
      activators compete with NADPH by filling the binding site of the adenine moiety
      of NADPH, but do not occupy the entire NADPH binding domain. Effects of these
      analogs on cNOS's include increasing the electron transfer rate to external
      acceptors, as assessed by cytochrome c reductase activity in the absence of
      calmodulin. In addition, NO synthase activity in the presence of calmodulin (with
      or without added calcium) was increased by the addition of NADPH analogs. In
      contrast, the same NADPH analogs inhibit iNOS, the calcium insensitive inducible
      isoform, which lacks control elements found in constitutive isoforms. Because ATP
      and ADP are among the effective activators of cNOS isoforms, these effects may be
      physiologically relevant.

PMID- 16412668
TI  - Analysis of family-level relationships in bees (Hymenoptera: Apiformes) using 28S
      and two previously unexplored nuclear genes: CAD and RNA polymerase II.
AB  - We analyzed a combined data set of two protein-coding nuclear genes (CAD and RNA
      polymerase II) and a nuclear ribosomal gene (28S D2-D4 region) for 68 bee species
      and 11 wasp outgroups. Our taxon sampling included all seven extant bee families,
      17 of 20 subfamilies, and diverse tribes. Wasp outgroups included the two
      families most closely related to bees: Crabronidae and Sphecidae. We analyzed the
      combined and single gene data sets using parsimony and Bayesian methods, which
      yielded largely congruent results. Our results provide reasonably strong support
      for family and subfamily-level relationships among bees. Our data set strongly
      supports the sister-group relationship of the Colletidae and Stenotritidae, and
      places Halictidae as sister to this clade combined. Our analyses place the
      Melittidae and the long-tongued (LT) bee clade (Apidae+Megachilidae) near the
      base of the tree with Colletidae (and Stenotritidae) in a fairly highly derived
      position. This topology ("Melittidae-LT basal") was obtained in previous
      morphological studies under certain methods of character coding. A more widely
      accepted tree topology that places Colletidae (and/or Stenotritidae) as sister to
      all other bees ("Colletidae basal") is not supported by our data. The "Melittidae
      LT basal" hypothesis may better explain patterns in the bee fossil record as well
      as historical biogeography of certain bee groups. Our results provide new
      insights into higher-level bee phylogeny and indicate that CAD, RNA polymerase
      II, and 28S are useful data sets for resolving Cretaceous-age divergences in bees
      and other Hymenoptera.

PMID- 16412671
TI  - Sensitivity quantification of remote detection NMR and MRI.
AB  - A sensitivity analysis is presented of the remote detection NMR technique, which
      facilitates the spatial separation of encoding and detection of spin
      magnetization. Three different cases are considered: remote detection of a
      transient signal that must be encoded point-by-point like a free induction decay,
      remote detection of an experiment where the transient dimension is reduced to one
      data point like phase encoding in an imaging experiment, and time-of-flight (TOF)
      flow visualization. For all cases, the sensitivity enhancement is proportional to
      the relative sensitivity between the remote detector and the circuit that is used
      for encoding. It is shown for the case of an encoded transient signal that the
      sensitivity does not scale unfavorably with the number of encoded points compared
      to direct detection. Remote enhancement scales as the square root of the ratio of
      corresponding relaxation times in the two detection environments. Thus, remote
      detection especially increases the sensitivity of imaging experiments of porous
      materials with large susceptibility gradients, which cause a rapid dephasing of
      transverse spin magnetization. Finally, TOF remote detection, in which the
      detection volume is smaller than the encoded fluid volume, allows partial images
      corresponding to different time intervals between encoding and detection to be
      recorded. These partial images, which contain information about the fluid
      displacement, can be recorded, in an ideal case, with the same sensitivity as the
      full image detected in a single step with a larger coil.

PMID- 16412672
TI  - Surface relaxation of polarized Xe atoms dissolved in deuterated ethanol.
AB  - We measured the spin relaxation of polarized xenon atoms dissolved in deuterated
      ethanol. Surface relaxation was suppressed by coating the cell walls with
      deuterated eicosane. From the dependence of the decay rate on temperature and
      static magnetic field, we obtained the correlation time of random fluctuations of
      the local field at the liquid-solid interface. By varying the cell volume, the
      wall coating, and the surface area of the eicosane, we measured the contribution
      of the spin-rotation interaction to the relaxation. The use of both deuterated
      molecules enables us to distinguish surface relaxation from the magnetic dipole
      dipole and spin-rotation interactions in solution.

PMID- 16412674
TI  - Contribution of intestine and kidney to glucose fluxes in different nutritional
      states in rat.
AB  - The liver is considered the main contributor of endogenous glucose production
      (EGP) in the postabsorptive (PA) state in mammals. However, it has been shown
      that the kidney, in PA and fasting states, and the intestine, in insulinopenia
      states, could make significant contributions to EGP. Using glucose tracer
      dilution combined to a vessel ligaturing approach, we studied the respective role
      of these organs in glucose turnover under various nutritional conditions in the
      rat (Rattus norvegicus). Both organs constitute key sites of glucose disposal in
      all situations in the non-moving rat. The kidney makes a small (12%) contribution
      to EGP in the PA state (9.6+/-1.3 micromol/kg min, means+/-SEM, n=5), which is
      dramatically increased (p<0.01) in 24 h-fasting (18.8+/-1.0 micromol/kg min) or
      streptozotocin diabetes (48+/-3 micromol/kg min). The small intestine contributes
      to EGP via two ways: a direct glucose contribution that may only take place in
      fasting and diabetes; an indirect contribution via the supply of alanine and
      lactate to liver gluconeogenesis that may account for up to 5 micromol/kg min in
      both PA and fasted states in the rat. These data emphasize the coordinate
      interactions among the three gluconeogenic organs in glucose homeostasis when
      nutritional conditions are changing.

PMID- 16412673
TI  - Functional characterization of parvalbumin from the Arctic cod (Boreogadus
      saida): similarity in calcium affinity among parvalbumins from polar teleosts.
AB  - Calcium dissociation constants (KD) were measured as a function of temperature
      for parvalbumin, a small acidic protein expressed abundantly in fast-twitch
      muscle, from the Arctic cod (Boreogadus saida) and compared to values previously
      determined for Antarctic and temperate zone teleosts. Estimates of KD were
      derived independently from fluorometric titrations and calorimetry. In addition,
      the primary structure of B. saida parvalbumin was determined. Calcium KDs for
      parvalbumin from B. saida were fundamentally similar to those for parvalbumins
      from Antarctic species (6.68+/-0.59 nM and 7.77+/-0.72 nM at 5 degrees C,
      respectively), but significantly different from temperate zone species (1.35+/
      0.28 nM at 5 degrees C). However, estimates of KD for B. saida parvalbumin at 5
      degrees C closely matched values for temperate zone fish at 25 degrees C (6.54+/
      0.56 nM), recapitulating the prior observation that calcium affinity of
      parvalbumin is conserved at the native temperature of teleost fish. Full sequence
      of B. saida parvalbumin was generated using reverse-phase HPLC and RACE-PCR. The
      Arctic parvalbumin showed 83% homology to a carp parvalbumin. None of the 16
      total substitutions between the two parvalbumins resided in the cation binding
      sites of the protein, indicating that the structural locus of the thermal
      sensitivity of function lies outside the active regions.

PMID- 16412675
TI  - Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the
      pyruvate dehydrogenase complex results in a milder phenotype.
AB  - Pyruvate dehydrogenase complex (PDC) deficiency is commonly due to mutations of
      PDHA1 on the X chromosome. Milder phenotypic manifestations occur in heterozygous
      females than in hemizygous males with the same mutation, and females are more
      likely to survive with severe mutations. The boy described here had hypotonia,
      moderate developmental delay, tremors, normal growth and brain MRI, and normal to
      slightly elevated lactate. PDC activity was low in skin fibroblasts and skeletal
      muscle (27-37%) but normal in lymphocytes. PDHA1 cDNA from cultured fibroblasts
      revealed two populations, one normal, the other lacking exon 6 (c.511-603 del).
      Genomic DNA from fibroblasts contained both normal and mutant (g.592G-->A)
      sequences within exon 6. Expression of minigene constructs containing exons 5, 6,
      and 7 with or without this mutation in 293T cells confirmed that the mutation
      alters splicing of exon 6. The mutant to wild-type DNA ratio varied substantially
      across tissues. Immunoblotting of fibroblast lysates detected only wild-type
      E1alpha protein. Immunocytochemistry of cultured skin fibroblasts showed a mosaic
      pattern with 60% of cells positive for E1alpha and 40% negative, consistent with
      PDC activity and DNA analysis. Karyotyping, FISH analyses, and genotyping
      revealed a 46XY male without chimerism. These data indicate somatic mosaicism for
      a mutation within exon 6 that causes exon skipping and production of a non
      functional protein. The mutated 592G residue is conserved among all eukaryotes.
      Substituting A for G apparently alters normal splicing by creating a SRp40 exonic
      splice enhancer site. The milder phenotype in this male is accounted for by the
      mixture of normal cells and cells lacking E1alpha. Immunocytochemistry was a
      useful adjunct to molecular analysis for demonstrating mosaicism.

PMID- 16412676
TI  - Antimicrobial therapy in pneumococcal meningitis: an epidemiological assessment
      from Turkey.

PMID- 16412677
TI  - Ultrastructural studies on antimicrobial efficacy of thyme essential oils on
      Listeria monocytogenes.
AB  - OBJECTIVES: Listeria monocytogenes has gained increasing attention as a pathogen
      of public health importance owing to large numbers of food-borne outbreaks of
      listeriosis. Because of negative consumer perception of chemical preservatives,
      attention is shifting towards natural alternatives. Particular interest has been
      focused on the potential application of plant essential oils. The objective of
      the present study was to determine ultrastructural changes brought about by
      essential oils from two types of thyme, Thymus eriocalyx and Thymus x-porlock, on
      Listeria monocytogenes. MATERIALS AND METHODS: Minimal inhibitory (MIC) and
      minimal bactericidal (MBC) concentrations and bactericidal kinetics of the oils
      were determined. Listeria monocytogenes were treated with essential oils from two
      thyme species and observed under a transmission electron microscope. RESULTS: The
      oils from the above plants were found to be strongly antimicrobial. Analysis of
      the oils by gas chromatography and gas chromatography/mass spectrometry lead to
      the identification of 18 and 19 components in T. eriocalyx and T. x-porlock oils,
      respectively. Listeria monocytogenes treated with essential oils from the two
      thyme species exhibited a thickened or disrupted cell wall with increased
      roughness and lack of cytoplasm. CONCLUSION: The antilisterial effects of thyme
      oil are stronger than the action of electric shocks in combination with nisin
      reported in the literature. It is concluded that essential oils such as thyme
      oil, which inhibited the growth of L. monocytogenes at low concentrations, could
      be considered as preservative materials for some kinds of foods; they could find
      an application as additives to foodstuffs in storage to protect them from
      listerial contamination.

PMID- 16412678
TI  - Evaluation of community-based serologic screening for identification of chronic
      Salmonella typhi carriers in Vietnam.
AB  - OBJECTIVES: To determine the utility of screening anti-Vi antibodies to detect
      chronic Salmonella Typhi carriers in an endemic community. METHODS: We conducted
      a community-based serologic survey for anti-Vi antibodies to identify chronic
      Salmonella Typhi carriers in a typhoid endemic region in Vietnam. RESULTS: We
      tested sera from 3209 (67.2%) of 4772 eligible adults. The median age was 37
      years (range 20-92), 57.3% were female, 4.6% reported a history of typhoid fever
      and 0.3% reported typhoid vaccination. Anti-Vi antibody titers tested in Vietnam
      were < 1:40 in 2759 (86.0%), 1:40 in 194 (6.0%), 1:80 in 168 (5.2%), 1:160 in 57
      (1.8%), and > or = 1:320 in 31 (1.0%). On re-testing in the USA, an additional 19
      sera with titers > or = 1:160 were identified. We collected 589 rectal swabs from
      103 (96.3%) of 107 persons with Vi antibody titers > or = 1:160 and 183 swabs
      from 33 persons with antibody titers < 1:80. No Salmonella Typhi was isolated.
      CONCLUSIONS: Community-based serologic screening is a feasible, but impractical
      method for identifying chronic Salmonella Typhi carriers. Background levels of
      anti-Vi antibody titers in this endemic area may be high despite a low prevalence
      of chronic carriers.

PMID- 16412679
TI  - Multidrug-resistant Pseudomonas aeruginosa infection in neutropenic patients
      successfully treated with a combination of polymyxin B and rifampin.

PMID- 16412680
TI  - An unusual presentation of acute brucellosis with fever, jaundice and
      maculopapular rash.

PMID- 16412681
TI  - Adult male circumcision to prevent HIV?
AB  - While the HIV pandemic persists, and randomized clinical trials to evaluate the
      effectiveness of male circumcision as an HIV prevention measure are underway with
      initial results being released, there is still much debate on the implications of
      these studies as well as on the feasibility of such a measure. This paper
      summarizes and discusses the main findings of studies of the evidence underlying
      adult male circumcision to prevent HIV, explores its feasibility and the
      implication for policy and future research. While the existing biological and
      epidemiological evidence suggest potential reduction of the risk of HIV
      acquisition in circumcised men, additional evidence from randomized trials are
      needed to confirm this. Even if the findings are confirmed, the practical aspects
      of implementing adult circumcision would have to be carefully considered. The
      feasibility of such an intervention, particularly with respect to its cost
      effectiveness, safety and acceptability, is still to be demonstrated.

PMID- 16412682
TI  - Delayed and misdiagnosis of wrist tuberculosis.

PMID- 16412683
TI  - DNA examination of ancient dental pulp incriminates typhoid fever as a probable
      cause of the Plague of Athens.
AB  - BACKGROUND: Until now, in the absence of direct microbiological evidence, the
      cause of the Plague of Athens has remained a matter of debate among scientists
      who have relied exclusively on Thucydides' narrations to introduce several
      possible diagnoses. A mass burial pit, unearthed in the Kerameikos ancient
      cemetery of Athens and dated back to the time of the plague outbreak (around 430
      BC), has provided the required skeletal material for the investigation of ancient
      microbial DNA. OBJECTIVE: To determine the probable cause of the Plague of
      Athens. METHOD: Dental pulp was our material of choice, since it has been proved
      to be an ideal DNA source of ancient septicemic microorganisms through its good
      vascularization, durability and natural sterility. RESULTS: Six DNA
      amplifications targeted at genomic parts of the agents of plague (Yersinia
      pestis), typhus (Rickettsia prowazekii), anthrax (Bacillus anthracis),
      tuberculosis (Mycobacterium tuberculosis), cowpox (cowpox virus) and cat-scratch
      disease (Bartonella henselae) failed to yield any product in 'suicide' reactions
      of DNA samples isolated from three ancient teeth. On the seventh such attempt,
      DNA sequences of Salmonella enterica serovar Typhi were identified providing
      clear evidence for the presence of that microorganism in the dental pulp of teeth
      recovered from the Kerameikos mass grave. CONCLUSION: The results of this study
      clearly implicate typhoid fever as a probable cause of the Plague of Athens.

PMID- 16412684
TI  - The increased ecto-5'-nucleotidase activity in muscle, heart and liver of laminin
      alpha2-deficient mice is not caused by an elevation in the mRNA content.
AB  - We have previously shown that mouse muscle and liver contain catalytically active
      and inactive ecto-5'-nucleotidase (eNT) variants and that eNT activity in these
      tissues increases in laminin alpha2 (merosin)-deficient Lama2dy mice. These
      results prompted us to study whether: (1) the increase of eNT activity depends on
      the change in the content of merosin between healthy and dystrophic organs; (2)
      the active and inactive eNT variants arise from the same or distinct mRNAs; (3)
      the enhancement of the activity is caused by an increase in the eNT mRNA content.
      Compared to healthy organs, the activity in dystrophic organs increased four-fold
      in muscle, 1.7-fold in liver, 1.4-fold in heart and not at all in kidney and
      lung. The level of immunolabelled eNT protein per unit of activity suggested a
      similar ratio of inactive to active eNT in healthy liver, kidney, heart and
      muscle, which increased greatly in lung. The size of the eNT subunit in liver,
      kidney, heart and muscle (72 kDa) decreased to 66 kDa in lung. The identification
      of a single RT-PCR product suggested that active and inactive eNT arise from the
      same mRNA and are generated by a differential post-translational processing.
      Compared to the content in muscle, the amount of eNT mRNA was 12-fold higher in
      liver and kidney, eight-fold in heart and five-fold in lung. The relative content
      of eNT mRNA was unaffected by the deficiency of merosin.

PMID- 16412685
TI  - DNA damage in leukocytes of workers occupationally exposed to 1-bromopropane.
AB  - 1-bromopropane (1-BP; n-propyl bromide) (CAS No. 106-94-5) is an alternative to
      ozone-depleting chlorofluorocarbons that has a variety of potential applications
      as a degreasing agent for metals and electronics, and as a solvent vehicle for
      spray adhesives. Its isomer, 2-brompropane (2-BP; isopropyl bromide) (CAS No. 75
      26-3) impairs antioxidant cellular defenses, enhances lipid peroxidation, and
      causes DNA damage in vitro. The present study had two aims. The first was to
      assess DNA damage in human leukocytes exposed in vitro to 1- or 2-BP. DNA damage
      was also assessed in peripheral leukocytes from workers with occupational
      exposure to 1-BP. In the latter assessment, start-of- and end-of-work week blood
      and urine samples were collected from 41 and 22 workers at two facilities where 1
      BP was used as a solvent for spray adhesives in foam cushion fabrication.
      Exposure to 1-BP was assessed from personal-breathing zone samples collected for
      1-3 days up to 8h per day for calculation of 8h time weighted average (TWA) 1-BP
      concentrations. Bromide (Br) was measured in blood and urine as a biomarker of
      exposure. Overall, 1-BP TWA concentrations ranged from 0.2 to 271 parts per
      million (ppm) at facility A, and from 4 to 27 ppm at facility B. The highest
      exposures were to workers classified as sprayers. 1-BP TWA concentrations were
      statistically significantly correlated with blood and urine Br concentrations.
      The comet assay was used to estimate DNA damage. In vitro, 1- or 2-BP induced a
      statistically significant increase in DNA damage at 1mM. In 1-BP exposed workers,
      start-of- and end-of-workweek comet endpoints were stratified based on job
      classification. There were no significant differences in DNA damage in leukocytes
      between workers classified as sprayers (high 1-BP exposure) and those classified
      as non-sprayers (low 1-BP exposure). At the facility with the high exposures,
      comparison of end-of-week values with start-of-week values using paired analysis
      revealed non-sprayers had significantly increased comet tail moments, and
      sprayers had significantly increased comet tail moment dispersion coefficients. A
      multivariate analysis included combining the data sets from both facilities, log
      transformation of 1-BP exposure indices, and the use of multiple linear
      regression models for each combination of DNA damage and exposure indices
      including exposure quartiles. The covariates were gender, age, smoking status,
      facility, and glutathione S-transferase M1 and T1 (GSTM1, GSTT1) polymorphisms.
      In the regression models, start-of-week comet tail moment in leukocytes was
      significantly associated with serum Br quartiles. End-of-week comet tail moment
      was significantly associated with 1-BP TWA quartiles, and serum Br quartiles.
      Gender, facility, and GSTM1 had a significant effect in one or more models.
      Additional associations were not identified from assessment of dispersion
      coefficients. In vitro and in vivo results provide limited evidence that 1-BP
      exposure may pose a small risk for increasing DNA damage.

PMID- 16412686
TI  - The infection risk of visceral leishmaniasis among household members of active
      patients.
AB  - Human visceral leishmaniasis (HVL), caused by Leishmania infantum is mainly
      observed as sporadic cases in Turkey and dogs are considered as the main
      reservoir of the disease. The incidence of visceral leishmaniasis among members
      of households where a HVL infection has already been diagnosed was studied in
      clusters around the diagnosed cases in different regions in Turkey. A total of 47
      serum samples collected from the households of 11 proven visceral leishmaniasis
      patients were screened for anti-Leishmania antibodies by indirect
      immunofluorescent antibody test (IFAT). Three and one such household members
      belonging to the different families were found to be seropositive and borderline,
      respectively. Diagnosis was confirmed with the presence of amastigotes in bone
      marrow aspiration samples in all seropositives while the borderline case with
      slight and indefinitive symptoms of VL was followed only serologically at 3-month
      intervals and improved spontaneously in 1 year. Household members of individuals
      with previously confirmed visceral leishmaniasis were found to have higher
      frequency of the disease suggesting the household members should be included in
      the risk group for visceral leishmaniasis and serological screening should be
      performed for the detection of possible infection.

PMID- 16412687
TI  - Force field calculations for 2-amino-5-chloro- and 2-amino-5-bromo
      benzotrifluorides.
AB  - Force field calculations have been carried out for 2-amino-5-chloro- and 2-amino
      5-bromo-benzotrifluorides using the earlier (Ref. of this article) reported IR
      and Raman spectra. As the frequencies of the corresponding modes for the C-Br and
      the C-Cl groups do not differ widely the two molecules are assumed to be
      isotopomers for the purpose of the force field calculations. The calculated and
      the observed frequencies match nicely for both the molecules. Consistent
      assignments have been proposed for the ring modes and the internal modes of the
      CF3 and the NH2 groups based on the potential energy distributions (PEDs), the IR
      and the Raman intensities and the depolarisation ratios of the Raman lines.

PMID- 16412688
TI  - Risk assessment of heterotrophic bacteria from bottled drinking water sold in
      Indian markets.
AB  - One hundred and five samples of bottled drinking water belonging to 30 different
      brands, collected from six different states of India have been analysed for total
      heterotrophic bacterial (THB) load and coliforms. Almost all bottlers used
      multiple treatment procedures such as microfiltration, reverse osmosis and
      ozonization to treat the water. Around 40% of the samples exceeded the limit of
      100 cfu/ml set by the department of health as well as Bureau of Indian Standards
      (BIS), Government of India. Fourteen percent and 44% of the samples with THB
      loads between 100 and 1000 cfu/ml or 1000 cfu/ml tested positive for coliforms
      indicating a linear relationship between THB and coliform bacteria. Gram-positive
      genera such as Kurthia and Corynebacterium were found to be dominant genera,
      while members of the family enterobacteriaceae contributed to 7%. Risk assessment
      of the heterotrophic bacteria revealed that the majority of the strains acquired
      resistance against ampicillin, nalidixic acid, novobiocin and oxytetracycline. As
      bottled drinking water is a ready to drink commodity, the high load of
      heterotrophic bacteria with multiple drug resistance poses significant health
      hazards to the consumers, especially to immunocompromised individuals.

PMID- 16412689
TI  - Pulmonary hypertension due to isolated metastatic squamous cell carcinoma
      thromboemboli.
AB  - Pulmonary hypertension as the initial presentation of occult malignancy is
      extremely rare. The differential diagnosis of pulmonary hypertension due to
      arterial tumour embolism is often overlooked and deserves contemplation. Our case
      report details the presentation of cardiorespiratory decompensation from an
      assumed classic saddle pulmonary embolus in a previously fit, well 80-year-old
      gentleman. The patient underwent successful pulmonary thromboendarterectomy,
      however, intraoperatively the specimen was noted to be atypical. This resulted in
      the surprising definitive diagnosis of thromboembolic pulmonary hypertension
      secondary to laminated thrombi of metastatic squamous cell tumour emboli. The
      site of tumour origin was however not histologically apparent and was unable to
      be elucidated on extensive further investigation. Post-operatively the patient
      had considerable subjective and functional improvement returning to activities of
      daily living. He however passed away some 9 months later.

PMID- 16412690
TI  - Genetic progress towards the molecular basis of autoimmunity.
AB  - The past few years have seen the identification of PTPN22 and the confirmation of
      CTLA-4 as common autoimmune disease genes. Together with MHC and INS, these
      developments have increased the collection of confirmed susceptibility loci for
      autoimmunity. In this article, the latest developments related to these genes and
      to other recently studied candidate autoimmune susceptibility loci (PDCD1, FCRL3,
      SUMO4, CD25, PADI4 and SLC22A4) are reviewed. Collectively, these genes strongly
      indicate that aberrant inhibition of the signalling cascade initiated by
      activation of the T-cell receptor is involved in the aetiology of autoimmune
      disease. However, much basic genetic, molecular and clinical research is still
      needed to help us fully understand the underlying mechanisms of autoimmunity and
      how these translate into prognosis or therapy.

PMID- 16412691
TI  - Quo vadis haemapheresis. Current developments in haemapheresis.
AB  - The techniques of haemapheresis originated in the development of centrifugal
      devices separating cells from plasma and later on plasma from cells. Subsequently
      membrane filtration was developed allowing for plasma-cell separation. The
      unspecificity of therapeutic plasma exchange led to the development of secondary
      plasma separation technologies being specific, semi-selective or selective such
      as adsorption, filtration or precipitation. In contrast on-line differential
      separation of cells is still under development. Whereas erythrocytapheresis,
      granulocytapheresis, lymphocytapheresis and stem cell apheresis are technically
      advanced, monocytapheresis may need further improvement. Also, indications such
      as erythrocytapheresis for the treatment of polycythaemia vera or photopheresis
      though being clinically effective and of considerable importance for an
      appropriate disease control are to some extent under debate as being either too
      costly or without sufficient understanding of the mechanism. Other forms of cell
      therapy are under development. Rheohaemapheresis as the most advanced technology
      of extracorporeal haemorheotherapy is a rapidly developing approach contributing
      to the treatment of microcirculatory diseases and tissue repair. Whereas the
      control of a considerable number of (auto-) antibody mediated diseases is beyond
      discussion, the indication of apheresis therapy for immune complex mediated
      diseases is quite often still under debate. Detoxification for artificial liver
      support advanced considerably during the last years, whereas conclusions on the
      efficacy of septicaemia treatment are debatable indeed. LDL-apheresis initiated
      in 1981 as immune apheresis is well established since 24 years, other semi
      selective or unspecific procedures, allowing for the elimination of LDL
      cholesterol among other plasma components are also being used. Correspondingly
      Lp(a) apheresis is available as a specific, highly efficient elimination
      procedure superior to techniques which also eliminate Lp(a). Quality control
      systems, more economical technologies as for instance by increasing automation,
      influencing the over-interpretation of evidence based medicine especially in
      patients with rare diseases without treatment alternative, more insight into the
      need of controlled clinical trials or alternatively improved diagnostic
      procedures are among others tools ways to expand the application of haemapheresis
      so far applied in cardiology, dermatology, haematology, immunology, nephrology,
      neurology, ophthalmology, otology, paediatrics, rheumatology, surgery and
      transfusion medicine.

PMID- 16412693
TI  - Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis.
AB  - OBJECTIVE: To determine whether all-trans-retinoic acid (ATRA) improves the
      destruction of joints and the effect of cytokines on DBA/1J mice with collagen
      induced arthritis (CIA). METHODS: Starting from the time of type II collagen
      injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA
      3 times per week for 35 days. The effects of treatment were monitored by
      determining arthritis and histological scores and measuring cellular
      proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and
      TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide
      synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3. RESULTS:
      The arthritis score and incidence of arthritis were lower in the mice treated
      with ATRA than in those treated with PBS. Histopathologic evidence of joint
      damage was 34% lower, and the infiltrations of macrophages were reduced in the
      mice treated with ATRA compared with those treated with PBS. Type II collagen-
      and ConA-stimulated proliferation of spleen cells, the production of cytokines
      (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti
      collagen antibodies, and the expression of mRNAs for MCP-1 were significantly
      reduced in the mice treated with ATRA than in those treated with PBS. CONCLUSION:
      ATRA improved the clinical course and reduced the production of inflammatory
      cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that
      ATRA might be also effective for the treatment of inflammatory arthritis like
      human rheumatoid arthritis.

PMID- 16412692
TI  - A quantitative model of error accumulation during PCR amplification.
AB  - The amplification of target DNA by the polymerase chain reaction (PCR) produces
      copies which may contain errors. Two sources of errors are associated with the
      PCR process: (1) editing errors that occur during DNA polymerase-catalyzed
      enzymatic copying and (2) errors due to DNA thermal damage. In this study a
      quantitative model of error frequencies is proposed and the role of reaction
      conditions is investigated. The errors which are ascribed to the polymerase
      depend on the efficiency of its editing function as well as the reaction
      conditions; specifically the temperature and the dNTP pool composition. Thermally
      induced errors stem mostly from three sources: A+G depurination, oxidative damage
      of guanine to 8-oxoG and cytosine deamination to uracil. The post-PCR
      modifications of sequences are primarily due to exposure of nucleic acids to
      elevated temperatures, especially if the DNA is in a single-stranded form. The
      proposed quantitative model predicts the accumulation of errors over the course
      of a PCR cycle. Thermal damage contributes significantly to the total errors;
      therefore consideration must be given to thermal management of the PCR process.

PMID- 16412694
TI  - Neuronal precursor-restricted transduction via in utero CNS gene delivery of a
      novel bipartite HSV amplicon/transposase hybrid vector.
AB  - The ability to modify genetically in utero the precursors of neuronal lineage
      contributing to multiple postmitotic cell types in the adult central nervous
      system would provide a means to evaluate strategies to ameliorate conditions
      affecting cellular patterning, metabolism, or survival. The herpes simplex virus
      (HSV)-derived amplicon, a vector devoid of viral genes and with the largest known
      payload capacity, normally exists episomally within nuclei of transduced cells,
      thus precluding conveyance during mitosis. Herein, we modify the Tc1-like
      Sleeping Beauty (SB) transposon system to create an integrating amplicon vector
      platform wherein provision of transposase in trans effectively catalyzes
      integration of a transgenomic segment. Cotransduction with a Rous sarcoma virus
      promoter-driven beta-galactosidase-neomycin (betageo) fusion flanked by SB
      terminal repeats (HSVT-betageo) and a second expressing the SB transposase gene
      under HSV immediate-early 4/5 gene promoter control (HSVsb) resulted in
      integration and extension of expression duration. Most notably, in utero
      intraventricular application led to extensive transgene expression within
      neuronal precursors and their derivatives without attendant adverse consequences,
      suggesting this new platform could be used to evaluate prenatally the function of
      gene products in neuronal lineages and evaluate therapeutic strategies for
      correction of genetic abnormalities affecting the developing CNS.

PMID- 16412695
TI  - Recombinant adeno-associated viral vectors as therapeutic agents to treat
      neurological disorders.
AB  - Recombinant adeno-associated virus (rAAV) is derived from a small human
      parvovirus with an excellent safety profile. In addition, this viral vector
      efficiently transduces and supports long-term transgene expression in the nervous
      system. These properties make rAAV a reasonable candidate vector for treating
      neurological disorders. Indeed, rAAV is currently being used in five early stage
      clinical trials for various neurodegenerative disorders. Therefore, we will
      review the currently available preclinical data using rAAV in animal models of
      central nervous system (CNS) disorders. Moreover, potential caveats for rAAV
      based gene therapy in the CNS are also presented.

PMID- 16412696
TI  - Memory performance during the intracarotid amobarbital procedure and
      neuropsychological assessment in medial temporal lobe epilepsy: the limits of
      material specificity.
AB  - We investigated the relationship between material-specific memory performance
      elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and
      classic neuropsychological assessment in 89 surgical candidates with refractory
      medial temporal lobe epilepsy (MTLE). The neuropsychological battery included
      measures of simple and complex verbal and visual memory, whereas the IAP material
      consisted of verbal and dually encodable stimuli. Neuropsychological testing
      revealed that reduced verbal memory performance was associated with left-sided
      MTLE, whereas visual memory tasks revealed no differences between patients with
      left-sided and right-sided MTLE. During IAP, memory performance was worse with
      the ipsilesional hemisphere, regardless of lesion side. Most importantly,
      performance on verbal memory tests was significantly, but moderately, correlated
      with left hemispheric IAP performance, indicating that memory tasks using verbal
      material are a valid marker of left hemispheric integrity in left language
      dominant MTLE patients and significantly predict left hemispheric memory
      performance during IAP. In contrast, performance on classic visual memory tests
      is unrelated to right hemispheric IAP performance, suggesting that the currently
      used visual memory stimuli do not reflect right hemispheric sensitivity.

PMID- 16412697
TI  - Protein and genomic organisation of vertebrate MyoR and Capsulin genes and their
      expression during avian development.
AB  - The related bHLH transcription factors MyoR and Capsulin control craniofacial
      myogenesis and the development of a number of mesoderm-derived organs in the
      mouse. However, their molecular function as regulators of differentiation
      processes is conversely debated. One approach to clarify the roles of these genes
      is to comparatively analyse their biological and molecular function in various
      vertebrate models. For this, a prerequisite is the determination of their
      similarity and their expression patterns. Here we show that vertebrate MyoR and
      Capsulin are paralogous genes with a high level of conservation regarding their
      protein sequence, their cDNA sequence and their chromosomal organisation. In the
      chick, both genes are co-expressed in the developing branchiomeric muscles, the
      anterior heart field and the splanchnopleura lining the foregut. However, both
      genes show unique expression domains in trunk skeletal muscle precursors, in the
      lateral and intermediate mesoderm.

PMID- 16412698
TI  - Differential expression pattern of coq-8 gene during development in
      Caenorhabditis elegans.
AB  - Coenzyme Q (Q) and the genes involved in its biosynthesis are involved in aging
      and development of Caenorhabditis elegans. Q is synthesized by at least eight
      highly conserved nuclear coq genes, but this biosynthesis pathway and its
      regulation is not known. The coq-8 gene sequence has homology to the ABC-1 family
      kinases and is the only known candidate for a possible regulation of this
      pathway. To study coq-8 expression pattern, we have developed a C. elegans
      transgenic strain expressing ubiquinone biosynthesis coq-8 gene promoter and GFP
      construct. We show here an age-dependent specific pattern from embryo to
      senescence for COQ-8 protein expression. Expression in embryo was triggered by a
      defined group of blastomers before morphogenesis. In elderly nematodes expression
      was only observed in nervous system, whilst expression in larvae was also
      detected in hypodermis, muscles and coelomocytes. Global expression provide a
      regulated pattern during life cycle of the nematode.

PMID- 16412699
TI  - Expression of Notch signaling pathway genes in mouse embryos lacking
      beta4galactosyltransferase-1.
AB  - A requirement for beta4galactosyltransferase-1 (beta4GalT-1) activity in the
      modulation of Notch signaling by the glycosyltransferase Fringe was previously
      identified in a mammalian co-culture assay. Notch signaling is necessary for the
      formation of somites in mammals. We therefore investigated the expression of
      eleven Notch pathway and somitogenic genes in E9.5 mouse embryos lacking
      beta4GalT-1. Four of these genes were altered in expression pattern or expression
      level. The Notch target genes Hes5 and Mesp2 were affected to some degree in all
      mutant embryos. The Notch ligand genes Dll1 and Dll3 were reduced or altered in
      expression in a significant proportion of mutants. While there were no
      differences in the number or morphology of somites in E9.5 B4galt1 null embryos,
      the number of lumbar vertebrae in mutant embryos differed from control
      littermates (P < or = 0.01). The subtlety of the in vivo phenotype may be due to
      redundancy since several B4galt genes related to B4galt1 are expressed during
      embryogenesis.

PMID- 16412700
TI  - Developmental and cell type-specific regulation of core promoter transcription
      factors in germ cells of frogs and mice.
AB  - This article reports on the comparative cell type-specific expression profiles of
      selected core promoter-associated transcription factors during gametogenesis and
      embryogenesis in frogs and mice. In frogs we tested TBP, TRF2/TLF, TRF3,
      TFIIAalphabeta, and ALF, as well as variant forms of TAFs 4, 5, and 6. Four of
      these factors, TRF3, TAF4L, TAF5L, and the previously-characterized ALF gene, are
      preferentially expressed in testis and ovary. In mice we tested TBP, TRF2/TLF,
      TRF3, TFIIAalphabeta, and ALF. The results showed that while ALF was present in
      testis and ovary, as expected, TRF3 could only be detected in the ovary. RT-PCR
      experiments using RNAs from microdissected ovary tissue, together with in situ
      hybridization analysis, showed that TRF3 and ALF genes are specifically expressed
      in oocytes in both adult and prepubertal animals, whereas, their somatic
      counterparts, TBP and TFIIAalphabeta, are present in oocytes and in surrounding
      somatic cells of the follicle. Furthermore, both mice and frogs displayed a
      reduction in TRF3 and ALF transcript levels around the time of fertilization. In
      mice, transcripts from these genes could again be detected at low levels in
      embryonic reproductive tissues, but only reached maximal levels in adult animals.
      Finally, the results of protein-DNA interaction assays show that all combinations
      of core promoter complexes can be formed in vitro using recombinant TBP, TRF3,
      TFIIA, and ALF, including a TRF3-ALF complex. Overall, the diverse gene
      regulatory patterns observed here and in earlier reports indicate precise control
      over which transcription factor complexes can be formed in vivo during
      gametogenesis and early embryogenesis.

PMID- 16412701
TI  - Expression of meiotic genes in the germline progenitors of Drosophila embryos.
AB  - Meiosis is one of the fundamental characteristics of germ cells. In Drosophila,
      genetic screens have identified many genes required for meiotic division.
      However, it remains elusive as to when and how these meiotic genes are activated
      during germline development. To obtain insights into their regulatory mechanisms,
      we examined the expression of 38 meiotic genes in the germline progenitors, pole
      cells, during embryogenesis. We found that the transcripts of 12 meiotic genes
      were enriched in pole cells within the embryonic gonads. Among them, bag of
      marbles (bam), benign gonial cell neoplasia (bgcn), deadhead (dhd), matotopetli
      (topi) and twine (twe) were activated only in pole cells within the gonads,
      whereas the transcripts from grapes (grp), Kinesin-like protein at 3A (Klp3A),
      pavarotti (pav), lesswright (lwr), mei-P26, Topoisomerase 2 (Top2) and out at
      first (oaf) were distributed ubiquitously in early embryos and then became
      restricted to pole cells and to a subset of somatic tissues at later embryonic
      stages. The remaining meiotic genes were either expressed ubiquitously in the
      embryos (15 genes) or were undetectable in pole cells within the gonads (11
      genes). These observations suggest that pole cells have already acquired the
      potential to express several meiotic genes. Our data will thus provide a useful
      basis for analyzing how the germline acquires a potential to execute meiosis.

PMID- 16412703
TI  - Individual human hair mitochondrial DNA control region heteroplasmy proportions
      in mothers and children.
AB  - Due to maternal inheritance, lack of recombination and a high polymorphic
      density, the mtDNA control region hypervariable (HV) regions are well suited for
      forensic identification using a maternal relative as the known sample. This
      analysis can be performed in hair, however, heteroplasmy in this tissue is not
      rare and can result in an apparent sequence mismatch that complicates this
      application. There is little data comparing mother and child mtDNA-CR
      heteroplasmic proportions in hair. In this study, we assayed four hairs per
      individual in 26 mother-child pairs by TTGE for heteroplasmy across HV1. Single
      nucleotide heteroplasmy was detected in seven families, and in four families at
      least two hairs were heteroplasmic. In each of the latter families, sequencing
      and PCR-RFLP confirmed single nucleotide heteroplasmy in proportions of the
      variant ranging from < or =10 to > or =90% in the mothers, with far less
      variability in their children. Sequencing alone would have revealed apparent
      homoplasmic differences at one nucleotide in these families, possibly resulting
      in an 'inconclusive' verdict for relatedness of child and mother. However, mother
      child heteroplasmic variability did not exceed intra-individual variability in
      the mothers alone.

PMID- 16412704
TI  - Phosphorylation of replication protein A by S-phase checkpoint kinases.
AB  - The major eukaryotic single-stranded DNA (ssDNA) binding protein, replication
      protein A (RPA), is a heterotrimer with subunits of 70, 32 and 14 kDa (RPA70,
      RPA32 and RPA14). RPA-coated ssDNA has been implicated as one of the triggers for
      intra-S-phase checkpoint activation. Phosphorylation of RPA occurs in cells with
      damaged DNA or stalled replication forks. Here we show that human RPA70 and RPA32
      can be phosphorylated by purified S-phase checkpoint kinases, ATR and Chk1. While
      ATR phosphorylates the N-terminus of RPA70, Chk1 preferentially phosphorylates
      RPA's major ssDNA binding domain. Chk1 phosphorylated RPA70 shows reduced ssDNA
      binding activity, and binding of RPA to ssDNA blocks Chk1 phosphorylation,
      suggesting that Chk1 and ssDNA compete for RPA's major ssDNA binding domain.
      ssDNA stimulates RPA32 phosphorylation by ATR in a length dependent manner.
      Furthermore, 3'-, but not 5'-, recessed single strand/double strand DNA junctions
      produce an even stronger stimulatory effect on RPA32 phosphorylation by ATR. This
      stimulation occurs for both RNA and DNA recessed ends. RPA's DNA binding polarity
      and its interaction to 3'-primer-template junctions contribute to efficient RPA32
      phosphorylation. Progression of DNA polymerase is able to block the accessibility
      of the 3'-recessed ends and prevent the stimulatory effects of primer-template
      junctions on RPA phosphorylation by ATR. We propose models for the role of RPA
      phosphorylation by Chk1 in S-phase checkpoint pathways, and the possible
      regulation of ATR activity by different nucleic acid structures.

PMID- 16412705
TI  - Mutagenesis and the three R's in yeast.
AB  - Mutagenesis is a prerequisite for evolution and also is an important contributor
      to human diseases. Most mutations in actively dividing cells originate during DNA
      replication as errors introduced when copying an undamaged DNA template or during
      the bypass of DNA lesions. In addition, mutations can be introduced during the
      repair of DNA double-strand breaks by either homologous recombination or non
      homologous end-joining pathways. Finally, although generally considered to be a
      very high-fidelity process, the excision repair of DNA damage may be an important
      contributor to mutagenesis in non-dividing cells. In this review, we will discuss
      the well-known contributions of DNA replication to mutagenesis in Saccharomyces
      cerevisiae, as well as the less-appreciated contributions of recombination and
      repair to mutagenesis in this organism.

PMID- 16412706
TI  - Early rise of anti-pseudomonas antibodies and a mucoid phenotype of pseudomonas
      aeruginosa are risk factors for development of chronic lung infection--a case
      control study.
AB  - P. aeruginosa is the most significant pathogen in CF lung disease. Chronic
      infection is preceded by a period of intermittent colonization. Early aggressive
      antimicrobial treatment at initial detection of P. aeruginosa in lower
      respiratory tract (LRT) secretions can prevent transition to chronic infection in
      approximately 80% of the patients, while the rest progress to chronic infection
      in spite of treatment. To analyze risk factors for development of chronic
      infection, a cohort of 89 CF patients free of chronic infection at the study
      period start was followed for 10 years. 28 of the patients (study group)
      developed chronic infection in spite of early treatment and 28 age-matched
      patients who did not (controls) were included in the analysis. During the 3 years
      period prior to onset of chronic infection, P. aeruginosa-positive cultures were
      more frequent in the study group than in the controls (2.2 vs. 0.5 per year,
      p<0.0001). Growth of mucoid strains of P. aeruginosa was more frequent in study
      group than in controls (11.5% vs. 0%, p<0.0001). Most important, specific anti
      pseudomonal IgG serum antibodies were significantly higher in the study group
      than in controls (0.98 Elisa Units vs. 0.53, p=0.04) already 3 years prior to
      onset of chronic infection and increased 0.44 EU pr year in the study group but
      remained at the initial level in the control group (p<0.005). Occurrence of
      Aspergillus-positive cultures were significantly more frequent in the study group
      than in controls (p=0.01). The strongest risk factor for development of chronic
      P. aeruginosa infection was increasing levels of specific anti-pseudomonal
      antibodies, specifically of IgG1 and IgG4 subclass and total anti-Pseudomonas
      IgG, 3 years prior to onset of chronic infection, with odds ratio (OR) 8.9, 7.7
      and 7.4, respectively (p<0.005), and growth of mucoid P. aeruginosa strains with
      OR of 7.4, p=0.006). Occurrence of Aspergillus was also a risk factor for
      developing chronic P. aeruginosa infection with the OR of 4.7 (p=0.008).

PMID- 16412708
TI  - Determination of free amino acids and related compounds in amniotic fluid by
      capillary electrophoresis with contactless conductivity detection.
AB  - A capillary electrophoretic (CE) method with contactless conductivity detection
      (CCD) has been developed for the determination of free amino acids (AAs) in the
      amniotic fluid. Apart from 20 proteinogenic AAs, 12 other biogenic compounds have
      been identified including ethanolamine, choline, beta-alanine, 2-aminobutyric
      acid, 4-aminobutyric acid, creatinine, ornithine, carnitine, citrulline, 4
      hydroxyproline, 1-methylhistidine and 3-methylhistidine. The running electrolyte
      consisted of 1.7 M acetic acid and 0.1% hydroxyethyl-cellulose (pH 2.15). An
      addition of acetonitrile to the sample improved the separation of AAs
      significantly and permitted an increase in the amount of the sample injected. As
      a result, the sensitivity of the determination increased and the limit of
      detection (LOD) decreased by a factor of ca. 4, as compared with our previous
      study. The LOD values were between 1.5 microM (arginine) and 6.7 microM (aspartic
      acid). The CE/CCD method has then been applied to clinical analyses of the
      amniotic fluid collected from 20 pregnant women aged over 35 years and 24
      pregnant women with whom abnormal foetus development was suspected. The latter
      group of women was found to exhibit systematically enhanced amniotic levels of
      most of the AAs studied.

PMID- 16412707
TI  - Theories on the nature of the coupling between ventilation and gas exchange
      during exercise.
AB  - For over a century of creative research, many theories on the possible mechanisms
      controlling respiration during exercise have been developed and discussed. One of
      the most enduring questions is certainly related to the mechanisms that can
      prevent P(a)(CO(2)) rising when CO(2) production increases. As multiple systems
      and structures are capable of increasing ventilation (V (E)), not all the
      mechanisms controlling respiration can provide a proper answer to this question.
      Indeed, exercise is a complex physiological condition combining motor activity
      with a change in metabolic rate. The most intriguing aspect of exercise is that
      when the changes in metabolism are dissociated from the motor and locomotor
      activity, the strategy 'chosen' by the respiratory control system is to follow
      the metabolic rate (or more precisely factors temporally associated with the
      pulmonary gas exchange rate) regardless of the motor act. The strategy used by
      the respiratory system during exercise therefore appears to select from among
      various sources of information the most relevant to follow the rate at which
      CO(2) is ultimately exchanged by the lungs. Yet, the nature of the signal(s)
      which prevents CO(2)/H(+) disturbance during exercise is the fundamental question
      addressed by this simple observation and remains to be clarified. This review
      illustrates the attempts of many physiologists to collect experimental evidence
      for theories which could provide satisfactory mechanisms accounting for the
      matching between ventilation and the rate at which CO(2) leaves the tissues and
      is exchanged at the lungs. More recent models based on somatic information of
      circulatory origin are presented and discussed.

PMID- 16412709
TI  - Liquid chromatography-electrospray ionization mass spectrometry for direct
      identification and quantification of iophenoxic acid in serum.
AB  - A liquid chromatographic-electrospray ionization mass spectrometric technique was
      developed for direct quantitation of iophenoxic acid (IA) in serum. IA was spiked
      into canine, feline, bovine, equine, and porcine sera, extracted, and quantified
      using negative ion monitoring following chromatographic separation on a Luna
      C18(2) 3 microm (100 mm x 2.1mm) reversed-phase column. The limit of detection
      was 25 ng/mL and the limit of quantification was 50 ng/mL. Inter- and intra-assay
      accuracy (86-113% and 87-115%, respectively) and precision (1.8-7.7%) were
      calculated. Analysis of serum collected from feral pigs, raccoons, and opossums
      following ingestion of IA-marked baits confirmed the appropriateness of this
      method for bait acceptance studies.

PMID- 16412710
TI  - Quantitation of zidovudine triphosphate concentrations from human peripheral
      blood mononuclear cells by anion exchange solid phase extraction and liquid
      chromatography-tandem mass spectroscopy; an indirect quantitation methodology.
AB  - To facilitate the assessment of drug safety and determination of phamacokinetics,
      an anion exchange isolation of zidovudine triphosphate (ZDV-TP) from human
      peripheral blood mononuclear cells (hPBMC), coupled with dephosphorylation,
      desaltation, and detection by liquid chromatography-tandem mass spectroscopy (LC
      MS-MS) was validated. hPBMCs were harvested from whole blood, lysed, and a
      suspension of intracellular ZDV-TP was produced. ZDV-TP was isolated from ZDV,
      ZDV-monophosphate (ZDV-MP), and ZDV-diphosphate (ZDV-DP), which were all present
      in the cell lysate, by performing a salt gradient anion exchange SPE. Isolated
      ZDV-TP was dephosphorylated with acid phosphatase to its parent drug form, ZDV.
      ZDV was then desalted and concentrated for tandem mass spectral detection. An LC
      MS-MS methodology was developed and validated for the determination of molar ZDV
      directly corresponding to the intra-hPBMC molar ZDV-TP concentration. ZDV-TP
      concentrations were determined in femtomoles per million hPBMCs
      (fmol/10(6)cells). The assay was able to determine ZDV-TP concentrations
      accurately and precisely within the range of 5-640 fmol/10(6)cells with 10
      million cells per sample analyzed. Inter- and intra-day accuracy and precision
      data for back calculated standards and quality controls fell within 15% of
      nominal. The assay correlated well with a previous ELISA method developed and
      validated in our laboratory, and has been successfully used to quantitate ZDV-TP
      concentrations in patients being routinely monitored and treated with ZDV.

PMID- 16412711
TI  - Simultaneous determination of six dialkylphosphates in urine by liquid
      chromatography tandem mass spectrometry.
AB  - Dialkylphosphates (DAP) are urinary markers of the exposure to organophosphates
      pesticides. The aim of this study was to develop a liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method for the simultaneous quantitative
      determination of the following DAP: dimethylphosphate (DMP), dimethythiophosphate
      (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP),
      diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP). Dibutylphosphate
      (DBP) was used as internal standard. This method was based on a liquid-liquid
      extraction procedure, a chromatographic separation using an Inertsil ODS3 C18
      column and mass spectrometric detection in the negative ion, multiple reaction
      monitoring (MRM) mode, following two ion transitions per compound. It yielded a
      limit of quantification of 2 microg/L for the six compounds and intra-assay
      coefficients of variation (CV%) lower than 20%. This method was applied to the
      analysis of urines samples from a small cohort of non-exposed volunteers. At
      least one of the six DAP was detected in each sample. This result confirmed the
      feasibility of a LC-MS/MS procedure for monitoring the general population
      exposure to some frequently employed organophosphate pesticides.

PMID- 16412712
TI  - Study on the binding of Arsenazo-TB to human serum albumin by Rayleigh light
      scattering technique and FT-IR.
AB  - The interaction between Arsenazo-TB and human serum albumin (HSA) was studied by
      Rayleigh light scattering (RLS) technique and Fourier transformed IR (FT-IR). The
      binding parameters of Arsenazo-TB with HSA were studied at different temperature
      of 288, 298, 308, 318 K under the optimum conditions. It is indicated by the
      Scatchard plots that the binding constant K decreased from 5.03 x 10(7) to 7.13 x
      10(6) and the maximum binding number N reduced from 53 to 36 with the increasing
      of the temperature. The binding process was exothermic, enthalpy driven and
      spontaneous, as indicated by the thermodynamic analyses, and the major part of
      the binding energy is hydrophobic interaction. The free energy change deltaG0,
      the enthalpy change deltaH0 and the entropy change deltaS0 of 288 K were
      calculated to be -42.46 kJ/mol, -49.17 kJ/mol and 318.15 J/mol K, respectively.
      The alterations of protein secondary structure in the presence of Arsenazo-TB in
      aqueous solution were quantitatively calculated from FT-IR spectroscopy with
      reductions of alpha-helix from 57% to 40% and with increases of beta-sheet from
      36% to 39%, beta-turn from 7% to 21%.

PMID- 16412713
TI  - Matricellular proteins: Extracellular modulators of bone development, remodeling,
      and regeneration.
AB  - Matricellular proteins are components of the extracellular matrix which are
      highly expressed in the developing and mature skeleton. Members of this protein
      class serve as biological mediators of cell function by interacting directly with
      cells or by modulating the activity of growth factors, proteases, and other
      extracellular matrix proteins. Although skeletons of matricellular protein-null
      mice are grossly normal, they each display unique deficiencies that are often
      magnified under pathological conditions. In addition, bone cells from wild-type
      and matricellular protein-null mice behave differently in various in vitro models
      of bone matrix synthesis and turnover. In this review, osteopontin, bone
      sialoprotein, tenascin C, SPARC, and thrombospondins 1 and 2 will each be
      discussed in the context of bone cell biology. Because the biological effects of
      matricellular proteins are largely context dependent, in vivo and in vitro
      results must be considered together in order to fully appreciate the specific
      contributions that matricellular proteins make to bone physiology and
      pathophysiology. In particular, it is clear that although matricellular proteins
      are not required for bone development and function, the proteins act to modulate
      post-natal bone structure in response to aging, ovariectomy, mechanical loading,
      and bone regeneration.

PMID- 16412714
TI  - Development and reversibility of impaired mineralization associated with
      lanthanum carbonate treatment in chronic renal failure rats.
AB  - BACKGROUND: We have previously shown that administration of the new phosphate
      binder lanthanum (La) carbonate at high doses during 12 weeks induces a
      mineralization defect (MD) in chronic renal failure (CRF) rats most likely due to
      the powerful phosphate binding. In this study, we want to investigate the fate
      and possible biological activities of La once it is accumulated in bone. METHODS:
      CRF animals (5/6th nephrectomy) received La carbonate (2,000 mg/kg/day) via oral
      gavage for 2 or 6 weeks and were sacrificed immediately at the end of the
      treatment period and after a wash out period of 2 and 8 weeks. Bone
      histomorphometry and measurement of bone La content were performed. Control CRF
      animals received vehicle only. RESULTS: After 2 weeks of La treatment, 75% of the
      animals showed signs of MD compared to 14% in CRF controls despite similar bone
      La levels. Two weeks after arrest of La treatment, bone La levels remained
      unchanged, yet 87% showed normal bone histology. A similar evolution was noted in
      the animals treated for 6 weeks. Bone histology showed a reduction of number of
      animals with a MD from 62.5% at 6 weeks of La treatment to 20% and 28% 2 and 8
      weeks after arrest of La treatment respectively. CONCLUSION: The phosphate-binder
      induced MD may appear and disappear without any change in either the perimeter of
      active osteoblasts or in bone La levels. Bone histology in CRF animals normalized
      after arrest of the La administration, thereby presenting further arguments for
      the MD in La-treated animals to result from the high phosphate binding capacity
      of La rather than being the consequence of a direct effect of La on bone.

PMID- 16412717
TI  - The management of postoperative ileus.

PMID- 16412718
TI  - Fertility preservation in female cancer patients: current developments and future
      directions.
AB  - OBJECTIVE: To review the current advances in fertility preservation strategies
      and to discuss future directions with an emphasis on ovarian tissue cryobanking.
      DESIGN: The publications related to fertility preservation in cancer patients
      were identified through Medline and other bibliographic databases, focusing on
      the most recent developments. CONCLUSION(S): There are several options for
      fertility preservation in cancer patients. Even though most of them are still
      experimental and their efficacy and reliability have not been determined, the
      future of fertility preservation in women with cancer is promising. In
      particular, the recent report of a live birth after transplantation of human
      ovarian tissue has reinforced the clinical potential of ovarian tissue banking
      for fertility preservation. Many exciting studies are underway to improve the
      efficacy and solve the problems with current fertility preservation strategies.
      It is inevitable that we will see the emergence of more complex ethical problems
      with the application of new technologies to humans. However, continuous efforts
      to improve current strategies and to develop new strategies will benefit many
      women and children who are facing premature ovarian failure and sterility.

PMID- 16412719
TI  - Turn, turn, turn.
AB  - Twenty years have passed since the publication in these pages of the oft-quoted
      editorial "The leader of the band is tired." At that time, the passing was
      mourned of the era of laparotomy for reconstructive pelvic surgery and the
      arrival of the laparoscope was heralded. Another transformation has occurred.
      Just as laparoscopy replaced laparotomy, all traditional treatments for
      infertility are being rendered obsolete by advanced reproductive technologies.

PMID- 16412720
TI  - Uterine artery embolization versus myomectomy: a multicenter comparative study.
AB  - OBJECTIVE: To determine whether there is significant quality of life score
      improvement after uterine artery embolization (UAE) and to compare UAE and
      myomectomy outcomes. DESIGN: Prospective cohort controlled study. SETTING:
      Sixteen medical centers in the United States. PATIENT(S): One hundred forty-nine
      UAE patients and 60 myomectomy patients. Patients were assigned to myomectomy or
      UAE on the basis of a best treatment decision made by the patient and her
      physician. All patients were observed for 6 months. The UAE patients also had
      follow-up examinations at 1 year. INTERVENTION(S): Myomectomy or UAE. MAIN
      OUTCOME MEASURE(S): Quality of life score changes, menstrual bleeding score
      changes, uterine size differences, time off, and adverse events. RESULT(S): Both
      groups experienced statistically significant improvements in the uterine fibroid
      quality of life score, menstrual bleeding, uterine volume, and overall
      postoperative quality of life. The mean hospital stay was 1 day for the UAE
      patients, compared with 2.5 days for the myomectomy patients. The UAE and
      myomectomy patients returned to their normal activities in 15 days and 44 days,
      respectively, and returned to work in 10 days and 37 days, respectively. At least
      one adverse event occurred in 40.1% of the myomectomy patients, compared with
      22.1% in the UAE group. CONCLUSION(S): The uterine fibroid quality of life score
      was significantly improved in both groups. No significant differences were
      observed in bleeding improvement, uterine volume reduction, uterine fibroid
      quality of life score improvement, and overall quality of life score improvement
      between groups. Patients receiving UAE required fewer days off work, fewer
      hospital days, and experienced fewer adverse events.

PMID- 16412721
TI  - Clinical outcomes of focused ultrasound surgery for the treatment of uterine
      fibroids.
AB  - OBJECTIVE: To assess outcomes at 6 and 12 months after magnetic resonance-guided
      focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas. DESIGN:
      Multicenter clinical trial. SETTING: Academic medical centers. PATIENT(S):
      Premenopausal women with symptomatic uterine leiomyomas and no plans for future
      pregnancy (n = 109 at 6 months and n = 82 at 12 months). INTERVENTION(S): A
      single treatment session of MRgFUS for uterine fibroids. MAIN OUTCOME MEASURE(S):
      Reduction in fibroid symptoms as measured by the symptom severity score (SSS) of
      the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated
      measure of leiomyoma symptomatology. A 10-point reduction in the SSS was selected
      as the targeted improvement. RESULT(S): Seventy-one percent of women undergoing
      MRgFUS reached the targeted symptom reduction at 6 months, and 51% reached this
      at 12 months. The magnitude of improvement in SSS was greater than predicted,
      with subjects having a mean decrease of 39% and 36% at 6 and 12 months,
      respectively. This paralleled the improvement seen using the short form-36
      instrument. A modest volume reduction similar in magnitude to the treated volume
      was seen. The incidence of adverse events was low. CONCLUSION(S): MRgFUS
      treatment results in short-term symptom reduction for women with symptomatic
      uterine leiomyomas with an excellent safety profile.

PMID- 16412722
TI  - Failure of uterine fibroid embolization.
AB  - OBJECTIVE: To assess the outcomes of patients who underwent uterine fibroid
      embolization (UFE) and to evaluate factors associated with failure of UFE.
      DESIGN: Retrospective study. SETTING: University teaching hospital. PATIENT(S):
      Two hundred thirty-three consecutive patients who underwent UFE from November
      1997 to February 2004. INTERVENTION(S): Uterine fibroid embolizations were
      performed by three interventional radiologists using 355-500-mu polyvinyl alcohol
      particles. MAIN OUTCOME MEASURE(S): Hysterectomy rate, myomectomy rate, and
      repeat UFE rate. RESULT(S): With a mean follow-up of 13 months, a total of 22
      patients underwent surgery after UFE (9.4%); 16 had hysterectomies (6.9%), and 6
      had myomectomies (2.6%). This included 3 patients who underwent repeat UFE and
      subsequently required surgical intervention. The mean (+/- SEM) time interval
      between UFE and subsequent treatment was 12.5 +/- 2.0 months. Among patients who
      required surgery, 13 (59.1%) presented with recurrent menorrhagia, and 5 (22.7%)
      complained of persistent abdominal pain. Histopathologic examination revealed
      concomitant findings of adenomyosis in 25% of hysterectomy specimens. Patients
      who failed UFE were more likely to have had a previous myomectomy (13% vs. 2.4%)
      and significant reduction in the uterine size 6 months after UFE (57.1% vs.
      25.2%). CONCLUSION(S): The overall failure rate of UFE is 9.4%. Failure is mainly
      due to persistent menorrhagia and abdominal pain. Shrinkage of the uterus after
      UFE does not necessarily correlate with long-term success of UFE.

PMID- 16412724
TI  - Management of leiomyomas: is there a panacea in Pandora's box?
AB  - New procedures and medications continue to be developed for the treatment of
      women with uterine leiomyomas; however, most are not adequately evaluated, and
      none is applicable in all circumstances. Appropriate management of uterine
      leiomyomas should be individualized, considering the related symptoms, as well as
      the number, size, and location of the tumors and the patient's desire regarding
      uterine conservation.

PMID- 16412723
TI  - Abdominal myomectomy in women with very large uterine size.
AB  - OBJECTIVE: To evaluate feasibility and safety of abdominal myomectomy with
      uterine myomas equal to or greater than 16 weeks in size. DESIGN: Retrospective
      chart review. SETTING: Private hospital. PATIENT(S): Women with uterine fibroids
      equal to or larger than 16 weeks in size. INTERVENTION(S): Abdominal myomectomy
      performed by one surgeon between March 1, 1998-February 28, 2003. MAIN OUTCOME
      MEASURE(S): Operating time, estimated blood loss, transfusion, cell-saver use,
      number and weight of fibroids removed, complications, pathology, and hospital
      stay were evaluated. RESULT(S): Ninety-one abdominal myomectomies met criteria.
      Mean operating time was 236 minutes (range, 120-390 minutes). Mean estimated
      blood loss was 794 mL (range, 50-3,000 mL). Seven (8%) women required homologous
      transfusion. Complications included one bowel injury, one bladder injury, one
      wound infection, and one reoperation for incarcerated small bowel. No woman had a
      uterine sarcoma or adenocarcinoma, and none required conversion to hysterectomy.
      CONCLUSION(S): Large uterine size does not preclude abdominal myomectomy and the
      results compare favorably with prior studies of hysterectomy for similar size
      uteri.

PMID- 16412725
TI  - New uterine-preserving therapies raise questions about interdisciplinary
      management and the role of surgery for symptomatic fibroids.
AB  - Mounting evidence to support the safety and effectiveness of new uterine
      preserving fibroid therapies is raising questions not only about changing
      indications for surgery but also about gynecologists' role in therapies offered
      by other specialists. New collaborative relationships are needed to provide the
      best possible treatment; without them, those lag times of 10-15 years often cited
      as the time it takes for advances in clinical research to diffuse into clinical
      practice will be even longer for women with symptomatic fibroids.

PMID- 16412726
TI  - Expanding treatment options for women with symptomatic uterine leiomyomas: timely
      medical breakthroughs.
AB  - Only during the last decade has there been a flourishing of alternative treatment
      options to major surgery for the management of symptomatic uterine leiomyoma. In
      addition to currently available minimally invasive surgical interventions, such
      as endometrial ablation techniques, radiologic interventions with uterine artery
      embolization and focused ultrasound surgery are welcome treatment options,
      despite the lack of long-term efficacy data.

PMID- 16412730
TI  - Preimplantation genetic diagnosis does not increase pregnancy rates in patients
      at risk for aneuploidy.
AB  - OBJECTIVE: To investigate the use of preimplantation genetic diagnosis (PGD) as a
      method for increasing pregnancy success rates in patients at high risk for
      aneuploidy. DESIGN: Literature review and discussion of current evidence.
      CONCLUSION(S): Preimplantation genetic diagnosis selects euploid embryos for
      transfer in assisted reproduction. Some investigators argue that it might be used
      to increase pregnancy rates in patient populations at high risk of aneuploidy,
      such as those with advanced maternal age (AMA), recurrent pregnancy loss (RPL),
      and recurrent IVF failure. Although analysis with PGD confirms a high rate of
      aneuploidy in patients with AMA, RPL, and recurrent IVF failure, its use in these
      patient populations has not been consistently shown, in the literature, to
      increase pregnancy rates. Randomized controlled trials with large patient
      populations, performed in programs with expertise in PGD technology, are needed
      before PGD can routinely be recommended as a means for increasing pregnancy rates
      in patients with AMA, RPL, and recurrent IVF failure.

PMID- 16412731
TI  - Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after
      use of a contraceptive vaginal ring and an oral contraceptive.
AB  - OBJECTIVE: To compare uterine tissue concentrations of ethinyl estradiol (EE) and
      etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring
      (NuvaRing; NV Organon, Oss, The Netherlands) or a combined oral contraceptive
      (COC). DESIGN: Randomized, open-label, pharmacokinetic study. SETTING: Obstetrics
      and gynecology unit. PATIENT(S): Eight premenopausal women about to undergo
      hysterectomy but otherwise healthy. INTERVENTION(S): One cycle (17-21 days) of
      NuvaRing or COC treatment that ended with surgical hysterectomy. MAIN OUTCOME
      MEASURE(S): Tissue concentrations of EE and ENG in uterine tissue samples taken
      from the upper myometrium and mid-myometrium, the cervical region, and the
      endometrium. RESULT(S): In both groups, concentrations of EE and ENG were similar
      in uterine tissue taken from the upper myometrium and mid-myometrium and the
      cervical region. However, compared with the COC group, concentrations of both
      hormones were markedly lower in tissue samples from the endometrium of women who
      had been treated with NuvaRing. CONCLUSION(S): Vaginal administration of hormones
      with NuvaRing did not produce elevated uterine concentrations of EE and ENG,
      compared with an oral contraceptive.

PMID- 16412732
TI  - Expression of the proto-oncoprotein breast cancer nuclear receptor auxiliary
      factor (Brx) is altered in eutopic endometrium of women with endometriosis.
AB  - OBJECTIVE: To evaluate the expression of estrogen receptor alpha (ERalpha),
      estrogen receptor beta (ERbeta), and breast cancer nuclear receptor auxiliary
      factor (Brx) in eutopic endometrium of normal women and women with endometriosis.
      DESIGN: Prospective observational study. SETTING: Tertiary care and research
      center. PATIENT(S): Twenty-nine women with endometriosis and 35 healthy ovulatory
      volunteers of similar ages. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME
      MEASURE(S): Expression of immunohistochemical staining intensity and localization
      of ERalpha, ERbeta, and Brx proteins in eutopic endometrium during the menstrual
      cycle. RESULT(S): Expression of ERalpha and ERbeta was highest in the
      proliferative phase and was similar in both groups. Brx expression differed
      between healthy volunteers and those with endometriosis. During the proliferative
      phase, immunostaining intensity of Brx was greater in both the glandular and the
      stromal compartments of biopsies from patients with endometriosis compared to
      healthy volunteers; nuclear stromal Brx staining was more common in patients with
      endometriosis. CONCLUSION(S): The spatiotemporal expression of Brx was altered in
      eutopic endometrium of women with endometriosis. These findings suggest a
      fundamental alteration in the endometrium of women who have endometriosis. The
      role of Brx in ectopic implantation of endometrium deserves further study.

PMID- 16412734
TI  - The endometria of patients with endometriosis show higher expression of class I
      human leukocyte antigen than the endometria of healthy women.
AB  - OBJECTIVE: To compare the expression of class I human leukocyte antigen (HLA I)
      in endometrial samples from patients with and without endometriosis. DESIGN:
      Cross-sectional study. SETTING: Acute-care teaching hospital in Barcelona, Spain.
      PATIENT(S): The endometriosis group included 32 patients for whom the only
      diagnosis during an operation was endometriosis. The control group included 20
      women who underwent a laparoscopy and in whom no evidence of endometriosis or any
      other genital disease was seen. INTERVENTION(S): Samples of endometrium were
      obtained by curettage and immediately frozen. A pan-HLA I mouse antihuman IgG2a
      monoclonal antibody was used for immunohistochemical study. MAIN OUTCOME
      MEASURE(S): Frequency of positive glandular and stromal cells was evaluated in
      each section. RESULT(S): A significantly higher expression of HLA I in the
      endometriosis group than in controls, both in the glandular cells (median 100%
      vs. 80%) and in the stromal cells (median 60% vs. 20%), was observed.
      CONCLUSION(S): Patients with endometriosis had a significantly higher expression
      of HLA I molecules in endometrial cells than did the controls. This could be a
      possible explanation for their higher resistance to natural killer cytolysis.

PMID- 16412733
TI  - Short synthetic endostatin peptides inhibit endothelial migration in vitro and
      endometriosis in a mouse model.
AB  - OBJECTIVE: To determine the active peptide regions inside the angiogenesis
      inhibitor endostatin that can inhibit endothelial migration in vitro and also
      inhibit endometriosis in a mouse model. DESIGN: Pharmacologic intervention in a
      surgically induced mouse model of endometriosis and endothelial migration assay.
      SETTING: Animal research and laboratory facility. SUBJECT(S): Eight-week-old,
      female C57BL/6 mice and human microvascular endothelial cells. INTERVENTION(S):
      Eight overlapping synthetic peptides were tested for inhibitory potential on
      endothelial migration in vitro. The peptides with significant activity then were
      given for 4 weeks to mice after implantation of autologous endometrium. MAIN
      OUTCOME MEASURE(S): Inhibition of vascular endothelial growth factor-induced
      endothelial migration for in vitro studies. In vivo studies examined the growth
      rate of endometriotic lesions after 4 weeks of treatment, as well as the effect
      on estrous cycling and ovulation as assessed by corpus luteum formation.
      RESULT(S): The N-terminal mP-1 peptide and the internal mP-6 peptide inhibited
      endothelial migration in a dose-dependent manner. Additionally, both synthetic
      peptides suppressed growth of endometriotic lesions significantly in vivo.
      However, estrous cycling and corpus luteum formation were normal in both groups.
      CONCLUSION(S): Short endostatin fragments may be promising as a new, nontoxic
      therapeutic strategy for the treatment of endometriosis without inhibition of
      normal estrous cycles.

PMID- 16412735
TI  - Maternal self-esteem after successful treatment for infertility.
AB  - OBJECTIVE: To [1] investigate self-esteem during pregnancy after previous
      infertility and [2] establish the relationship among self-esteem, anxiety during
      pregnancy, and parenting self-efficacy. DESIGN: Limited prospective study.
      SETTING: A regional infertility clinic and antenatal clinic. PATIENT(S): Seventy
      women who had conceived through assisted reproductive technology and 111 women
      who had conceived naturally. INTERVENTION(S): Measures of self-esteem, anxiety,
      and parenting self-efficacy. MAIN OUTCOME MEASURE(S): Self-esteem, anxiety, and
      parenting self-efficacy. RESULT(S): Women who had conceived through IVF treatment
      did not differ in terms of self-esteem during pregnancy from those who had
      conceived naturally. All of the women in the present study displayed levels of
      self-esteem that were within the normal range. Self-esteem increased as pregnancy
      progressed. Self-esteem was negatively correlated with anxiety during pregnancy.
      As self-esteem increased, anxiety decreased. Self-esteem at the start of
      pregnancy (18 weeks) and anxiety in the early stages of parenthood (6 weeks
      postpartum) predicted parenting self-efficacy. CONCLUSION(S): Self-esteem in the
      early stages of pregnancy, for both women who conceived through IVF and women who
      conceived naturally, is related to self-reported levels of parenting efficacy.
      Coaching and mentoring through antenatal clinics in the early stages of pregnancy
      should be tailored to incorporate advice regarding self-esteem in addition to
      management of pregnancy and psychological well-being.

PMID- 16412736
TI  - First cesarean birth and subsequent fertility.
AB  - OBJECTIVE: To determine whether cesarean delivery is independently associated
      with later subfertility. DESIGN: Retrospective cohort study. SETTING: Maternity
      records kept for Scotland, 1980-1999. PATIENT(S): The study included 109,991
      women who had first births between 1980 and 1984, excluding multiple or preterm
      births and perinatal deaths. INTERVENTION(S): Exposures studied were spontaneous
      vaginal birth, operative vaginal birth, planned cesarean delivery for breach
      presentation, planned cesarean delivery for other indications, and emergency
      cesarean delivery. MAIN OUTCOME MEASURE(S): The relative risk of not having a
      second pregnancy over the following 15 years, the interpregnancy interval, and
      the number of spontaneous early pregnancy losses between the first and second
      birth. RESULT(S): Women who delivered by planned cesarean section for breech
      presentation had an increased risk of not having a second birth compared with
      women whose first birth was a spontaneous vertex delivery (relative risk [RR]:
      1.21, 95% confidence interval [CI]: 1.14 to 1.29). However, after adjustment for
      maternal and obstetric characteristics, there was no longer a strong association
      (adjusted RR: 1.07, 95% CI: 1.00 to 1.15). Operative vaginal delivery (forceps
      and vacuum extraction) and all types of cesarean delivery were associated with
      longer interpregnancy intervals. There was no relationship between mode of
      delivery and the number of spontaneous early pregnancy losses between the first
      and second birth. CONCLUSION(S): It is unlikely that delivering by cesarean
      section in a first pregnancy decreases a woman's likelihood of having a second
      viable pregnancy.

PMID- 16412737
TI  - Comparison of unilateral and bilateral transfer of injected oocytes into
      fallopian tubes: a prospective, randomized clinical trial.
AB  - OBJECTIVE: To assess whether pregnancy rate differs in unilateral vs. bilateral
      transfer in "immediate transfer of injected oocytes into the fallopian tubes."
      DESIGN: Prospective randomized clinical trial. SETTING: Tertiary university
      hospital. PATIENT(S): The study population included 160 patients presenting with
      male factor infertility who fulfilled the criteria for immediate transfer of
      injected oocytes into tubes. INTERVENTION(S): Four injected oocytes were
      transferred into two tubes (study group) or one tube (control group). MAIN
      OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, multiple
      pregnancy rate, and incidence of pregnancy with unknown location (PUL).
      RESULT(S): A total of 72 (45%) pregnancies were achieved. There were 32
      pregnancies (1 PUL, 4 multiple, and 27 singletons) in the bilateral transfer
      group and 40 pregnancies in the unilateral transfer group (1 PUL, 7 multiple, and
      32 singletons). No significant difference was found in the implantation rate,
      clinical pregnancy rate, multiple pregnancy rate, and incidence of PUL.
      CONCLUSION(S): This study demonstrates that no difference in outcome occurred
      between unilateral and bilateral transfer in microinjected oocytes intrafallopian
      transfer (MIFT). Therefore, along with the same outcome parameters, unilateral
      transfer is the preferred method of MIFT.

PMID- 16412738
TI  - Proteomic analysis of individual human embryos to identify novel biomarkers of
      development and viability.
AB  - OBJECTIVE: To develop a method to analyze the proteome of individual human
      blastocysts and identify differentially expressed proteins prior to implantation.
      DESIGN: Experimental study. SETTING: Research environment. PATIENT(S): Couples
      undergoing infertility treatment donated with consent cryopreserved human
      cleavage-stage embryos for research. INTERVENTION(S): Individual embryos were
      extracted and analyzed by time-of-flight mass spectrometry. MAIN OUTCOME
      MEASURE(S): The protein expression profiles of individual embryos. RESULT(S):
      Differential protein expression profiles were observed between early and expanded
      blastocysts, as well as between developing blastocysts and degenerate embryos.
      Significantly, several up-regulated and down-regulated proteins were detected in
      degenerating embryos. A search in the protein databases highlighted several
      candidates, including an inhibitor of Tcf-4 (transcription factor mediating Wnt
      signaling) and an apoptotic protease-activating factor. CONCLUSION(S): This is
      the first study to successfully analyze the proteome of individual human embryos.
      This study has shown that protein expression profiles relate to morphology, with
      degenerating embryos exhibiting significant up-regulation of several potential
      biomarkers that might be involved in apoptotic and growth-inhibiting pathways.

PMID- 16412739
TI  - Successful ongoing pregnancies after vitrification of oocytes.
AB  - OBJECTIVE: To demonstrate the efficiency of vitrifying mature human oocytes for
      different clinical indications. DESIGN: Descriptive case series. SETTING:
      Cryobiology laboratory, Centro Colombiano de Fertilidad y Esterilidad-CECOLFES
      LTDA. (Bogota, Colombia). PATIENT(S): Oocyte vitrification was offered as an
      alternative management for patients undergoing infertility treatment because of
      ovarian hyperstimulation syndrome, premature ovarian failure, natural ovarian
      failure, male factor, poor response, or oocyte donation. Mature oocytes were
      obtained from 33 donor women and 40 patients undergoing infertility treatment.
      INTERVENTION(S): Oocytes were retrieved by ultrasound-guided transvaginal
      aspiration and vitrified with the Cryotops method, with 30% ethylene glycol, 30%
      dimethyl sulfoxide, and 0.5 mol/L sucrose. Viability was assessed 3 hours after
      thawing. The surviving oocytes were inseminated by intracytoplasmic sperm
      injection. Fertilization was evaluated after 24 hours. The zygotes were further
      cultured in vitro for up to 72 hours until time of embryo transfer. MAIN OUTCOME
      MEASURE(S): Recovery, viability, fertilization, and pregnancy rates. RESULT(S):
      Oocyte vitrification with the Cryotop method resulted in high rates of recovery,
      viability, fertilization, cleavage, and ongoing pregnancy. CONCLUSION(S):
      Vitrification with the Cryotop method is an efficient, fast, and economical
      method for oocyte cryopreservation that offers high rates of survival,
      fertilization, embryo development, and ongoing normal pregnancies, providing a
      new alternative for the management of female infertility.

PMID- 16412740
TI  - Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing
      gonadotropin-releasing hormone antagonist in vitro fertilization cycles.
AB  - OBJECTIVE: To determine the incidence of ovarian hyperstimulation syndrome (OHSS)
      in a large series of GnRH antagonist-stimulated cycles and to assess the
      predictive value of E2 and the number of follicles on the day of hCG
      administration. DESIGN: Prospective cohort study of women undergoing IVF
      treatment with a GnRH antagonist protocol over a 2-year period. SETTING: Tertiary
      university hospital. PATIENT(S): One thousand eight hundred one patients who
      underwent 2,524 cycles. INTERVENTION(S): Multifollicular ovarian stimulation with
      recombinant FSH and GnRH antagonist for IVF-ICSI treatment. MAIN OUTCOME
      MEASURE(S): Incidence of OHSS in GnRH antagonist cycles, predictive value of E2,
      and number of follicles on the day of hCG for OHSS occurrence. RESULT(S): Fifty
      three patients were hospitalized because of OHSS (2.1%; 95% confidence interval
      [CI]:1.6-2.8). Early OHSS presented in 31 patients (1.2%; 95% CI: 0.9-1.8),
      whereas the late type was a complication in 22 patients (0.9%; 95% CI: 0.5-1.3).
      Late OHSS cases compared with the early OHSS cases always occurred in a pregnancy
      cycle (100% vs. 40%); had higher probability of being severe (72.7% vs. 42%), and
      more often were related to a multiple pregnancy (40% vs. 0). Receiver operating
      characteristic curve analysis for several E2 concentrations and number of
      follicles with a diameter of > or =11 mm revealed that the predictive value of
      the optimal threshold of > or =13 follicles (85.5% sensitivity; 69% specificity)
      was statistically significantly superior to the optimal threshold of 2,560 ng/L
      for E2 concentrations (53% sensitivity, 77% specificity) in identifying patients
      at risk for OHSS. Considering that severe OHSS represents the most clinically
      significant pattern, the combination of a threshold of > or =18 follicles and/or
      E2 of > or =5,000 ng/L yields a 83% sensitivity rate with a specificity as high
      as 84% for the severe OHSS cases. CONCLUSION(S): Clinically significant OHSS
      still remains a limitation of multifollicular ovarian stimulation for IVF even
      with the use of GnRH antagonist protocols. The number of follicles can
      discriminate the patients who are at risk for developing OHSS, whereas E2
      concentrations are less reliable for the purpose of prediction. There is more
      than ever an urgent need for alternative final oocyte maturation-triggering
      medication.

PMID- 16412741
TI  - Dimensional assessment of X-bearing and Y-bearing haploid and disomic human sperm
      with the use of fluorescence in situ hybridization and objective morphometry.
AB  - OBJECTIVE: To explore the dimensional attributes of haploid and disomic X-bearing
      and Y-bearing spermatozoa. DESIGN: Morphometric evaluation of more than 2,000 X
      bearing and Y-bearing spermatozoa after identification of the genotype with
      fluorescence in situ hybridization. SETTING: Academic clinical and research
      andrology laboratory. MAIN OUTCOME MEASURE(S): Sperm head area, perimeter, long
      axis, short axis, shape factor, elliptical form factor (long axis/short axis),
      and tail length. RESULT(S): We found no differences in dimensions or dimensional
      distributions between X-bearing and Y-bearing spermatozoa, whether in the native
      or the decondensed state, or in oligozoospermic or normozoospermic men. There
      were inconsistent differences and a 70% overlap in the dimensions of haploid and
      disomic spermatozoa. The other 30% of sperm with disomic nuclei were either
      smaller or larger compared to haploid spermatozoa. CONCLUSION(S): There are no
      differences, or distinguishing characteristics, in dimensions or dimensional
      distributions between X-bearing and Y-bearing spermatozoa. Dimensional attributes
      do not discriminate between dysomic and haploid spermatozoa.

PMID- 16412742
TI  - Within- and between-subject variation in semen parameters in infertile men and
      normal semen donors.
AB  - OBJECTIVE: To determine within- and between-subject variation of semen parameters
      in infertile and normal men. DESIGN: Retrospective analysis of 74 infertile men
      and 65 normal men producing five or more ejaculates each. SETTING: Clinical
      andrology laboratory. SUBJECT(S): Men presenting to an infertility clinic for
      semen analysis and normal men providing donor semen for cryopreservation.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Within-subject coefficients of
      variation (CVw) and between-subject coefficients of variation (CVb), calculated
      for sperm count, motility, and velocity, semen volume, and motility and velocity
      after cryopreservation. RESULT(S): The number of ejaculates ranged 5-20 in
      patients (479 total) and 5-136 in donors (2,043 total). Sperm counts, motility,
      and velocity were statistically greater in donors, whereas semen volume was
      significantly greater in patients. The CVw in patients and donors was greatest in
      sperm counts (54.2% and 45.8%, respectively) and lowest in velocity (20.1% and
      19.9%, respectively). The CVb in patients and donors was markedly higher than CVw
      for all parameters in both patients and donors. The CVw was lower, and the CVb
      was higher, in donors compared with patients. The CVw was not affected by age of
      the individual or abstinence period. Cryopreservation resulted in a marked
      increase in variability. Intraclass correlations indicated that a minimum of
      three semen samples were required to achieve reliability. CONCLUSION(S): These
      data indicate large within- and between-subject variation in sperm parameters,
      especially sperm count, in both patients and healthy donors, and further
      substantiate the need for measurement of multiple ejaculates before
      characterizing a man as normal or infertile.

PMID- 16412743
TI  - Increased frequency of cystic fibrosis transmembrane conductance regulator gene
      mutations in infertile males.
AB  - OBJECTIVE: To investigate the frequency of mutations of the cystic fibrosis
      transmembrane regulator (CFTR) gene in males with reduced sperm quality before
      intracytoplasmic sperm injection (ICSI). DESIGN: The nine most frequent cystic
      fibrosis-causing mutations in the German population and IVS8T alleles were
      analyzed. SETTING: University-based centers for reproductive medicine and
      clinical genetics. PATIENT(S): An unselected group of 597 males with oligo-,
      astheno-, terato-, crypto-, oligoasthenoteratozoospermia, or azoospermia, which
      underwent pre-ICSI genetic counseling over a 5-year period. INTERVENTION(S):
      Blood samples were collected from the patients during genetic counseling. MAIN
      OUTCOME MEASURE(S): Frequency of mutations of CFTR gene in infertile males.
      RESULT(S): A heterozygous CFTR mutation was observed in 34 of 597 patients
      (5.70%). None of the patients had two CFTR mutations. Given that our mutation
      panel recognizes about 82% of heterozygotes, it can be assumed that the frequency
      of CFTR heterozygotes in our cohort is about 6.94%. The frequency of CFTR
      mutations in our cohort did not correlate with a reduced sperm count.
      CONCLUSION(S): The frequency of cystic fibrosis in the German population is
      1:3300. Thus, a CFTR heterozygosity of 3.42% can be estimated. This indicates
      that in our cohort of infertile males, the frequency of CFTR heterozygosity is
      twofold higher than in the general population (P<.0001).

PMID- 16412744
TI  - Alterations of sexual desire and satisfaction in male partners of infertile
      couples.
AB  - OBJECTIVE: To clarify the state of sexual desire and satisfaction, with relevant
      parameters in men, of couples with infertility. DESIGN: Cross-sectional study.
      SETTING: University outpatient clinic. PATIENT(S): Two hundred infertile couples
      referred to a reproductive health research clinic. INTERVENTION(S): Patients were
      investigated by a self-administered structured questionnaire about demographic
      data, infertility history, and several relevant psychological variables. In
      addition, clinical and andrological examinations were completed to find
      predictors for sexual state. MAIN OUTCOME MEASUREMENT(S): Sexual desire and
      satisfaction status were scaled, and the relative factors were analyzed
      statistically. RESULT(S): Subjects reported a reduction in sexual desire in 41.5%
      of cases and reduction of satisfaction in 52.5% compared with recalled sexual
      satisfaction before diagnosis of infertility. No relationship was found between
      andrological findings and the present status of sexual desire (P>.05). Education
      level, mutual understanding between couples, and recalled state of sexual
      satisfaction had a direct influence, but the duration of infertility and duration
      of desire for a child showed a significant inverse impact on sexual satisfaction
      (P<.05). CONCLUSION(S): Less than 50.0% of patients mentioned a reduction in
      sexual desire and satisfaction after infertility diagnosis, and the frequency of
      coitus could be regarded as an acceptable indicator of sexual satisfaction in
      male partners of infertile couples.

PMID- 16412745
TI  - Cytosolic calcium levels in spermatozoa are modulated differently in healthy
      subjects and patients with varicocele.
AB  - OBJECTIVE: To study parameters connected to fertility in the semen of patients
      with varicocele. DESIGN: We examine the ability of spermatozoa obtained from
      patients with varicocele to respond with an increase of cytosolic Ca2+ ([Ca2+]i)
      to some stimuli that are connected with spermatozoa activation. SETTING: An
      academic research environment. PATIENT(S): Ten healthy volunteer donors and 10
      patients affected by II or III grade left varicocele. INTERVENTION(S):
      Spermatozoa and prostasomes (vesicles of prostatic origin obtained from semen)
      were prepared according to standard procedures. Spermatozoa were stimulated with
      1 microM P. The [Ca2+]i was evaluated with the FURA II method. MAIN OUTCOME
      MEASURE(S): The level of [Ca2+]i. RESULT(S): In resting cells, the level of
      [Ca2+]i was 120 +/-15 nmol/L (10 determinations). This value increases by > or
      =100 nmol/L upon stimulation with P. No difference was observed between
      spermatozoa obtained from healthy donors or from patients with varicocele. S
      nitrosocysteine, a nitric oxide donor, and the fusion between spermatozoa and
      prostasomes increased the effect of P on [Ca2+]i in control spermatozoa but not
      in spermatozoa obtained from patients with varicocele. CONCLUSION(S): Different
      responsiveness of varicocele patients' spermatozoa to S-nitrosocysteine and/or to
      fusion with prostasomes may be among the possible causes of reduced fertility.

PMID- 16412746
TI  - Mitochondrial membrane potential integrity and plasma membrane translocation of
      phosphatidylserine as early apoptotic markers: a comparison of two different
      sperm subpopulations.
AB  - OBJECTIVE: To examine whether a relationship exists between loss of mitochondrial
      transmembrane potential and plasma membrane translocation of phosphatidylserine
      (PS) in subpopulations of human spermatozoa of men consulting for infertility.
      SETTING: A tertiary institutional research center. DESIGN: Prospective
      observational study. PATIENT(S): Twelve infertile men and five fertile controls
      were compared. INTERVENTION(S): Sperm subpopulations were compared after density
      gradient separation. MAIN OUTCOME MEASURE(S): Mitochondrial membrane potential
      was measured with a cationic dye, translocation of PS was evaluated with Annexin
      V binding, and motion parameters were assessed manually. RESULT(S): In both the
      study and control groups and compared with the high-motility fraction, the low
      motility fraction had significantly lower sperm motility and normal morphology,
      and significantly higher percentage of cells with disrupted mitochondrial
      membrane potential and plasma membrane PS translocation. There was a positive and
      significant correlation in both subfertile and control groups between the
      percentages of Annexin-V+ live cells and cells with mitochondrial membrane
      potential disruption (r = 0.82 and r = 0.85, respectively). CONCLUSION(S): The
      correlation of plasma membrane PS translocation and loss of mitochondrial
      membrane potential is suggestive of an early apoptosis phenotype, as is typically
      observed in somatic cells identified in sperm subpopulations with percentage of
      low-motile cells. We speculate that such changes might be used as diagnostic
      markers of sperm dysfunction(s) and that increased levels found in subfertile men
      might be indicators of reduced fertility potential.

PMID- 16412747
TI  - A randomized comparative study of the effects of oral and topical estrogen
      therapy on the lower urinary tract of hysterectomized postmenopausal women.
AB  - OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on
      the lower urinary tract in postmenopausal women with prior hysterectomy. DESIGN:
      Randomized, prospective study. SETTING: Tertiary teaching hospital. PATIENT(S):
      Fifty-seven hysterectomized, postmenopausal women. INTERVENTION(S): Patients were
      randomized to receive either oral (0.625 mg of conjugated equine E per tablet; n
      = 27) or topical (0.625 mg conjugated equine E per 1 g vaginal cream; n = 30) E,
      administered once daily. MAIN OUTCOME MEASURE(S): All subjects had E2
      measurements, urinalysis, pelvic examination, introital color Doppler
      ultrasonographies, and personal interviews with the Bristol Female Lower Urinary
      Tract Symptoms Questionnaires before and 3 months after ET. RESULT(S): A higher
      serum level of E2 was noted in the oral group compared with the topical group
      after ET. The post-ET pulsatility index of periurethral vessels and bladder neck
      revealed statistically significant decreases in both groups. The incidences of
      urinary frequency and nocturia were significantly decreased after 3 months of ET
      in both groups. Changes in the incidence of other symptoms, including stress
      incontinence and urge incontinence, were not statistically significant. However,
      subjective improvement of stress incontinence was found in 72.7% of the oral
      group and 60% of the topical group. CONCLUSION(S): The results suggest that ET
      alone, by an oral or vaginal route, could increase the blood flow around the
      bladder neck and mid-urethra and relieve the symptoms of overactive bladder and
      stress incontinence in postmenopausal women with prior hysterectomy. In addition,
      vaginal preparations are as effective as systemic therapy at the lower serum
      level of E2.

PMID- 16412748
TI  - A randomized trial of superovulation with two different doses of letrozole.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of either a 2.5-mg
      or a 5-mg daily dose of letrozole in women undergoing superovulation and
      intrauterine insemination (IUI). DESIGN: Prospective randomized trial. SETTING:
      Academic teaching hospital. PATIENT(S): Women <40 years old, with patent
      fallopian tubes and infertility of >1 year in duration. INTERVENTION(S): Patients
      were randomized into either a 2.5-mg dose of letrozole (34 patients) or a 5-mg
      dose of letrozole (38 patients) daily for 5 days. When the leading follicle
      reached 18 mm in diameter, ovulation was triggered by an injection of hCG and IUI
      was performed 24 and 48 hours later. MAIN OUTCOME MEASURE(S): The number of
      follicles, endometrial thickness, and pregnancy rate. RESULT(S): Compared with
      those treated with 2.5 mg of letrozole, the total number of follicles was
      significantly higher in patients receiving 5 mg of letrozole. No difference in
      the endometrial thickness was found between the two groups. The pregnancy rate
      per cycle in patients receiving 5mg of letrozole was statistically higher than in
      patients receiving 2.5 mg of letrozole (26.3% vs. 5.9%, P<.05). No multiple
      pregnancies occurred. CONCLUSION(S): Compared with the daily dose of 2.5 mg, 5 mg
      of letrozole is associated with more follicles and a higher pregnancy rate. It
      appears that 5 mg daily for 5 days is a preferable letrozole dose for
      superovulation.

PMID- 16412749
TI  - Preliminary prospective study of the endocrinology of conception cycles and early
      pregnancy in women with antiphospholipid syndrome treated with low molecular
      weight heparin.
AB  - OBJECTIVE: To examine whether there were any differences in the endocrinological
      profiles during conception cycle and early pregnancy between a control group and
      women with a history of recurrent miscarriage that was caused by antiphospholipid
      syndrome and that was treated with aspirin and low molecular weight heparin.
      DESIGN: Prospective observational study. SETTING: Recurrent Miscarriage Clinic,
      Department of Obstetrics and Gynaecology in a tertiary care centre. PATIENT(S):
      Five women with recurrent pregnancy loss were recruited as cases, whereas another
      five women having natural cycle donor insemination were used as control.
      INTERVENTION(S): Serial measurement of serum beta-hCG, activin A, and inhibin A
      was performed from postovulatory day 12 until 11 weeks of gestation. MAIN OUTCOME
      MEASURE(S): Comparison of levels of beta-hCG, activin A, and inhibin A at the
      time of conception onwards till 11 weeks in the two groups. RESULT(S): There were
      no significant differences between the two groups. CONCLUSION(S): There does not
      appear to be any obvious endocrinological alteration in the conception cycle of
      women with antiphospholipid syndrome compared with a control group. Furthermore,
      the initiation of heparin does not produce a significant change in activin A and
      inhibin A levels.

PMID- 16412750
TI  - Expression of heparin-binding epidermal growth factor-like growth factor and its
      receptors in the human fallopian tube and endometrium after treatment with
      mifepristone.
AB  - OBJECTIVE: To study the effect of mifepristone on heparin-binding epidermal
      growth factor (HB-EGF) and its receptors HER1 and HER4 in the fallopian tube and
      in the endometrium. DESIGN: Prospective clinical study. SETTING: Hospital-based
      unit for obstetrics and gynecology and research laboratories. PATIENT(S): Healthy
      women divided into two groups: controls and patients treated with a single dose
      of 200 mg mifepristone on day LH+2. INTERVENTION(S): Endometrial biopsies from 30
      women were obtained during one control cycle or one treatment cycle. Fallopian
      tubes from 14 women were collected during laparoscopic sterilizations. MAIN
      OUTCOME MEASURE(S): Immunohistochemistry and reverse transcriptase-polymerase
      chain reaction. RESULT(S): The staining intensity of HB-EGF was not affected by
      mifepristone treatment. Treatment with mifepristone increased the immunostaining
      on HER1 in the epithelium and the stroma of the endometrium, which was not seen
      in the fallopian tube. The immunostaining of HER4 decreased in the stroma of the
      fallopian tube, while an increase was seen in the epithelial cells of the
      endometrium. CONCLUSION(S): Treatment with mifepristone has a limited effect on
      HB-EGF and its receptors in the fallopian tube, while the increase in HER1 and
      HER4 in the endometrium probably reflects defective endometrial maturation.

PMID- 16412751
TI  - Spatial differences in biologic activity of large uterine leiomyomata.
AB  - OBJECTIVE: To evaluate the growth pattern of the large uterine leiomyomata (ULM),
      we examined the spatial gene distributions, vessel density, proliferative
      activity, and hyaline degeneration. DESIGN: Tissue sections from three
      dimensional large ULM, matched myometrium, and small ULM were collected and
      microarrayed. The spatial difference of the tumor activity was mapped in large
      ULM. SETTING: University clinical research laboratory. PATIENT(S): Hysterectomy
      specimens from 7 patients with large (>10 cm) ULM and 3 patients with large (>10
      cm) uterine leiomyosarcomas. INTERVENTION(S): Tissue microarray analysis by the
      immunohistochemistry. MAIN OUTCOME MEASURE(S): Selected gene products, vessel
      density, and the percentage of hyaline degeneration were all scored in tissue
      cores/sections of large and small ULM against matched myometrium. RESULT(S): We
      found that there was a spherical spatial difference of the tumor activities in
      large ULM. The tumor region next to the periphery, the most biologically active
      zone, demonstrated higher levels of gene expression, a higher density of vessels,
      a higher proliferative rate and a lower level of hyaline degeneration. The large
      ULM have higher levels of gene products (except for estrogen and progesterone
      receptors) than small ULM. CONCLUSION(S): In comparison of the spatial patterns
      of the gene activity between the large ULM and the large uterine leiomyosarcoma,
      the large ULM illustrate a growth pattern of nutritional dependence.

PMID- 16412752
TI  - Expression of alpha 1 and beta 3 integrins subunits in the endometrium of
      patients with tubal phimosis or hydrosalpinx.
AB  - OBJECTIVE: To determine the expression of alpha1 and beta3 integrin subunit on
      the endometrium of infertile patients with hydrosalpinx and infertile patients
      with tubal phimosis. DESIGN: Case-control study. SETTING: Tertiary medical
      center. PATIENT(S): Infertile patients with radiologic or laparoscopic diagnosis
      of hydrosalpinx (n = 11) or tubal phimosis (n = 12) as the only cause of
      infertility, and fertile controls (n = 17). INTERVENTION(S): Immunohistochemical
      analysis of alpha1 and beta3 integrin subunits was performed on endometrial
      biopsies obtained during the implantation window. MAIN OUTCOME MEASURE(S):
      Histologic score (HSCORE) on luminal and glandular endometrium of the patients
      with hydrosalpinx or tubal phimosis and the normal fertile controls. RESULT(S):
      The median (+/-SEM) HSCORE for beta3 subunit expression in endometrial glands was
      0.39 +/- 0.23 and 0.42 +/- 0.18 for tubal phimosis and hydrosalpinx,
      respectively, and 1.74 +/- 0.26 for fertile controls. The median HSCORE for beta3
      subunit expression in luminal epithelium for tubal phimosis, hydrosalpinx, and
      fertile controls was 0.07 +/- 0.06, 0.21 +/- 0.18, and 1.03 +/- 0.31,
      respectively. No statistical difference was observed on the expression of alpha1
      integrin subunit expression between the three groups. CONCLUSION(S): The
      endometrial expression of beta3 integrin subunit is reduced in the presence of
      tubal phimosis or hydrosalpinx, during the window of implantation.

PMID- 16412753
TI  - Gene expression profiling of early follicular development in primordial, primary,
      and secondary follicles.
AB  - OBJECTIVE: To study global gene expression profiles of early folliculogenesis in
      primordial, primary, and secondary follicles. DESIGN: A cDNA microarray study
      using amplified RNAs from isolated follicles. SETTING: Experimental animal study.
      ANIMAL(S): Female ICR strain mice (12 days old). INTERVENTION(S): Isolation of
      follicles at each stage, RNA isolation and amplification, microarray
      hybridization, and statistical analysis for microarray. MAIN OUTCOME MEASURE(S):
      Gene lists of various functional groups with an estimated false discovery rate of
      5%. Among them, platelet-derived growth factors (PDGFs) and receptors were
      localized by immunohistochemistry in mouse ovaries. RESULT(S): We analyzed a list
      of genes according to function, such as apoptosis, cell cycle, cell proliferation
      and maintenance, cytoskeleton, extracellular matrix, and signal transduction, as
      well as according to frequency. Among the list of genes, we found all PDGFs (A,
      B, C, and D) and receptors (alpha and beta) are expressed with differential
      expression patterns in the oocytes and ovarian cells according to stage of
      follicular development. CONCLUSION(S): The present report suggests that genome
      wide expression profiling using microarray after RNA amplification may become a
      useful tool to better understand the molecular mechanism(s) involved in early
      ovarian folliculogenesis.

PMID- 16412754
TI  - Oral contraceptives maintain a very thin endometrium before operative
      hysteroscopy.
AB  - OBJECTIVE: To show that early follicular-phase administration of an oral
      contraceptive pill (OC) consistently provides a thin endometrium, as determined
      by transvaginal ultrasound. This is an ideal condition when performing operative
      hysteroscopy. DESIGN: Retrospective chart review of patients who have undergone
      ultrasound evaluation of the endometrial thickness under different hormonal
      conditions. Endometrial measurement was obtained during menstruation, in the late
      follicular phase, and in the luteal phase in 20 patients. In another group of 100
      patients, endometrial measurement was made on the 18th day of OC administration,
      initiated during menses. SETTING: A reproductive endocrinology unit in a
      university-affiliated medical center. PATIENT(S): Patients undergoing treatment
      for subfertility of various etiologies. INTERVENTION(S): Transvaginal ultrasound
      measurements of the endometrium. MAIN OUTCOME MEASURE(S): Endometrial thickness
      by transvaginal ultrasound. RESULT(S): Combination OCs started on menstrual days
      1-3 maintain a uniformly thin endometrium, 4.1 +/- 1.6 mm (mean +/- SD),
      comparable to menstrual endometrium (3.7 +/- 1.5 mm). This was statistically
      thinner compared with endometrium observed in the late follicular phase (11 +/-
      2.0 mm) or late luteal phase (12 +/- 2.3 mm). Transvaginal ultrasound
      measurements of the endometrium under different conditions were compared by the
      unpaired t-test. CONCLUSION(S): Oral contraceptives maintain a very thin, flat
      endometrium, such that lesions might be readily identified and treated during
      operative hysteroscopy procedures. Prevention of pregnancy and endometrial
      thinning with administration of OCs facilitates procedural scheduling for
      patients and surgeons.

PMID- 16412755
TI  - Cryopreservation of spermatozoa in alginic acid capsules.
AB  - OBJECTIVE: To develop a method of freezing small amounts of spermatozoa in
      polymerized alginic acid drops, which can be liquified after thawing for recovery
      of the spermatozoa. DESIGN: Prospective clinical study. SETTING: Medical School,
      RWTH Aachen, Aachen Germany. PATIENT(S): None. INTERVENTION(S): Validation of the
      encapsulation method with bovine sperm; cryopreservation of human spermatozoa in
      alginic capsules. MAIN OUTCOME MEASURE(S): We optimized the cryopreservation
      method by testing different parameters influencing the freezing procedure, such
      as concentration of alginic acid, size of drops, time of polymerization, and
      culture media. RESULT(S): The final protocol was as follows: encapsulation by 7.3
      mg/mL alginic acid forming 10-muL drops polymerized for 30 seconds and liquefied
      for 2.5 minutes in sodium citrate. Cryopreservation of human spermatozoa by this
      protocol resulted in a decreased motility of 18.3% compared with standard
      protocols but a 19.9% higher vitality of the immotile spermatozoa. CONCLUSION(S):
      No difference in viability of spermatozoa after both sperm-freezing procedures
      could be observed. Further investigation will be undertaken to reduce the amount
      of immotile but viable sperm after microencapsulation in alginic acid.

PMID- 16412756
TI  - Diagnosis of polycystic ovaries by three-dimensional transvaginal ultrasound.
AB  - OBJECTIVE: To study diagnostic thresholds for polycystic ovary (PCO). DESIGN:
      Retrospective cohort study. SETTING: Academic hospital. PATIENT(S):
      Normoandrogenic ovulatory women and patients with polycystic ovary syndrome
      (PCOS). INTERVENTION(S): Two-dimensional (2D) and three-dimensional (3D)
      transvaginal ultrasound. MAIN OUTCOME MEASURE(S): The mean follicle number per
      ovary (FNPO) of both ovaries and the maximum number follicles in a single
      sonographic plane (FSSP) of either ovary were determined using 3D transvaginal
      ultrasound. Ovarian volume was determined using 2D transvaginal ultrasound.
      RESULT(S): Twenty-nine normoandrogenic ovulatory women were compared with 10
      patients with PCOS. Diagnostic thresholds for PCO with 100% specificity as
      determined by receiver operator characteristic (ROC) curves were > or =20 for
      mean FNPO, > or =10 for maximum FSSP, and > or =13 cm3 for ovarian volume. Both
      2D and 3D transvaginal ultrasound were highly accurate in the diagnosis of PCO as
      determined by areas under the curve (AUC) that were >90% for all three measures.
      CONCLUSION(S): Mean FNPO and maximum FSSP by 3D transvaginal ultrasound have
      comparable high accuracy for diagnosis of PCO. The diagnostic threshold with 100%
      specificity for mean FNPO is > or =20, which is greater than suggested by the
      Rotterdam Consensus Workshop in 2003. Use of the consensus standard,
      consequently, may result in overdiagnosis of PCO. A threshold of > or =20 mean
      FNPO using 3D transvaginal ultrasound may be appropriate to minimize false
      positive diagnoses of PCO.

PMID- 16412757
TI  - Computer-aided evaluation of assessment of "grade a" spermatozoa by experienced
      technicians.
AB  - OBJECTIVE: To determine how well technicians assess progressively motile
      spermatozoa. DESIGN: Comparison of computerized and technician assessments of
      "grade a" spermatozoa. SETTING: University fertility clinic. PATIENT(S):
      Infertile men of barren marriages. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Threshold velocities of spermatozoa categorized as "grade a."
      RESULT(S): The ability of andrology technicians to distinguish "grade a" from
      "grade b" spermatozoa was examined monthly. Computer-aided sperm analysis (CASA)
      provided the threshold velocities used by technicians to categorize "grade a"
      spermatozoa. The mean cutoff value for grades a/b (25.5 microm/s) was close to
      the designated velocity, but the cutoff for grades b/c sperm (9.9 microm/s) was
      higher. Cutoff values for "grade a" spermatozoa were significantly, positively,
      and linearly related with the mean velocity of spermatozoa obtained by CASA, and
      deviated from it in a systematic way. The percentage of "grade a" spermatozoa
      judged by technicians was poorly correlated with the percentage "grade a"
      indicated by CASA and the cutoff velocity of "grade a" spermatozoa depending on
      the overall sperm quality of the semen sample. CONCLUSION(S): Consideration
      should be given to replacing the subdivision of progressing spermatozoa into two
      categories with one of progressive spermatozoa, or the use of CASA to distinguish
      "grade a" sperm reliably should be insisted upon.

PMID- 16412758
TI  - Uterine adenomyoma presenting as a vesico-uterine endometrioma.
AB  - This is an image case report of a 5-cm uterine adenomyoma in a 38-year-old
      asymptomatic woman, presenting as a vesico-uterine endometrioma in both
      ultrasound scan and magnetic resonance imaging.

PMID- 16412759
TI  - Higher-order multiple pregnancy associated with metformin in women with
      polycystic ovary syndrome: two cases and review of the literature.
AB  - OBJECTIVE: To describe the first reported cases of two women with polycystic
      ovary syndrome (PCOS) desirous of pregnancy who conceived trichorionic
      pregnancies following ovulation induction with metformin alone and metformin plus
      clomiphene. DESIGN: Case report. SETTING: Private fertility practice. PATIENT(S):
      Two women with polycystic ovary syndrome, one lean and one overweight, both
      oligoovulatory and not undertaking their first cycle of treatment.
      INTERVENTION(S): Ovulation induction by metformin alone or in combination with
      clomiphene MAIN OUTCOME MEASURE(S): Higher-order multiple pregnancy (triplet or
      greater). RESULT(S): Two cases of trichorionic pregnancy. CONCLUSION(S): This is
      the first report of higher-order multiple pregnancies resulting from the use of
      either metformin alone or in combination with clomiphene. The additive effects of
      adjunctive treatments such as weight reduction, ovarian drilling, and clomiphene
      and metformin therapy may result in an increased incidence of higher-order
      multiple pregnancy and women need to be counseled about this risk. Further
      research is required to quantify the risk of this event per treatment cycle.

PMID- 16412760
TI  - A steroid cell tumor outside the ovary is a rare cause of virilization.
AB  - OBJECTIVE: To report the case of a female who presented in childhood with
      symptoms and signs of hyperandrogenism secondary to an extraovarian steroid cell
      tumor. DESIGN: Case report. SETTING: Endocrine investigation unit of a university
      teaching hospital. PATIENT(S): An 11-year-old female presented with symptoms and
      signs of hyperandrogenism. INTERVENTION(S): Ultrasonography, MRI imaging,
      bilateral adrenal and ovarian venous sampling, laparoscopy, and laparotomy. MAIN
      OUTCOME MEASURE(S): Ultrasonography, laboratory tests. RESULT(S):
      Hyperandrogenism was due to an extraovarian steroid cell tumor located in the
      broad ligament. The tumor was successfully removed at laparotomy with biochemical
      and clinical resolution of the hyperandrogenism. CONCLUSION(S): Extraovarian
      steroid cell tumor is a rare cause of hyperandrogenism.

PMID- 16412761
TI  - Complications after fertility-preserving radical trachelectomy.
AB  - OBJECTIVE: We report a case of cervical cancer treated by radical trachelectomy
      complicated by pelvic inflammatory disease, tubo-ovarian complex, and
      infertility. DESIGN: Case report. SETTING: Tertiary referral university hospital.
      PATIENT(S): A 35-year-old with stage IB1 cervical cancer underwent an uneventful
      radical vaginal trachelectomy. Three years later she presented with pelvic pain
      and fever after a new partner. Cervical chlamydia was positive, and sonography
      showed bilateral complex adnexal masses. Her symptoms resolved with prolonged IV,
      followed by oral, antibiotics. Temperature, cultures, and blood tests have all
      normalized but her sonogram demonstrates persistent bilateral hydrosalpinx. She
      has not conceived and underwent laparoscopic salpingectomy prior to IVF. She
      remains cancer free. INTERVENTION(S): Radical vaginal trachelectomy,
      salpingectomy and assisted reproductive techniques. MAIN OUTCOME MEASURE(S):
      Cancer disease status and fertility preservation. RESULT(S): Three years later,
      the patient remains cancer free but has been unable to conceive or carry a
      pregnancy. CONCLUSION(S): Fertility-preserving cancer treatments are relatively
      new. Complications may be encountered that must be reported, collected, and
      analyzed to maximize cancer cure and fertility preservation.

PMID- 16412762
TI  - Cullen's sign following ultrasound-guided transvaginal oocyte retrieval.
AB  - OBJECTIVE: To describe two cases of periumbilical hematoma (Cullen's sign)
      following ultrasound-guided transvaginal oocyte retrieval. DESIGN: Case report.
      SETTING: University-affiliated teaching hospital. PATIENT(S): Two patients, 34
      and 32 years old, who developed Cullen's sign following ultrasound-guided
      transvaginal oocyte retrieval. INTERVENTION(S): Workup for pancreatitis and
      coagulopathies. Laparoscopy was preformed in one patient. MAIN OUTCOME
      MEASURE(S): Resolution of the symptoms. RESULT(S): Pancreatitis, coagulopathy,
      and massive hemoperitoneum were ruled out. Symptoms resided within two weeks.
      CONCLUSION(S): The appearance of a periumbilical hematoma (Cullen's sign)
      following ultrasound-guided transvaginal oocyte retrieval reflects a
      retroperitoneal hematoma of a benign course.

PMID- 16412764
TI  - GR/GR deletions within the azoospermia factor c region on the Y chromosome might
      not be associated with spermatogenic failure.
AB  - No statistically significant difference in deletion frequency was found between
      infertile patients and a control group. It is suggested that in some populations
      the gr/gr deletion might be an inconsequential polymorphism.

PMID- 16412763
TI  - Pregnancy after embolization therapy for uterine arteriovenous malformation.
AB  - OBJECTIVE: To describe childbearing prognosis following embolization therapy for
      uterine arteriovenous malformation (AVM). DESIGN: Case report and review.
      SETTING: University hospital. PATIENT(S): Thirteen patients, including our case,
      who underwent pregnancy after embolization therapy for arteriovenous
      malformation. INTERVENTION(S): Two successive embolization procedures. MAIN
      OUTCOME MEASURE(S): Childbearing prognosis following embolization therapy for
      uterine AVM. RESULT(S): Bilateral embolization was performed in seven patients.
      In four cases, including ours, two successive embolization procedures were
      required to treat the uterine AVM. The longest delay between embolization and
      pregnancy was 5 years and the shortest was six weeks. Two patients presented with
      postpartum hemorrhage which was treated medically. One neonate required
      resuscitation after delivery in the context of Listeria infection. CONCLUSION(S):
      Conservative management of uterine AVMs using embolization therapy is being
      increasingly developed. New embolization agents and hyperselective technical
      procedures aim at reducing morbidity related to such treatments and preserving
      reproductive capacity in women of childbearing age.

PMID- 16412765
TI  - Disruption of the SLC26A3-mediated anion transport is associated with male
      subfertility.
AB  - Male subfertility in congenital chloride diarrhea (CLD) was possible after
      identification of expression of an epithelial Cl-/HCO3- exchanger SLC26A3 in the
      male reproductive tract and by the observation that adult men with CLD had very
      few children. A prospective clinical and laboratory study among eight adult
      Finnish men with CLD revealed constant oligoasthenoteratozoospermia but normal
      spermatogenesis, high chloride and low pH in seminal plasma, and three
      spermatoceles, suggesting that male subfertility is a clinical manifestation of
      CLD and could be caused by an analogous defect in the epithelial Cl-/HCO3- and
      water transport, as described for the CLD intestine.

PMID- 16412766
TI  - Frequency of chromosomal abnormalities in spontaneous abortions derived from
      intracytoplasmic sperm injection compared with those from in vitro fertilization.
AB  - No statistical difference was found for the total aneuploidy rate in the
      spontaneous abortions between intracytoplasmic sperm injection and IVF groups;
      however, differences in the distribution of chromosomal abnormalities between the
      two groups were seen.

PMID- 16412767
TI  - Ketotifen improves sperm motility and sperm morphology in male patients with
      leukocytospermia and unexplained infertility.
AB  - In an open, uncontrolled study, the effect of 12 weeks of daily administration of
      ketotifen, an antihistamine-like drug with a mast cell stabilizing effect, on the
      semen quality of 55 men with leukocytospermia and unexplained infertility was
      examined. After 4 weeks of treatment, white blood cell count dramatically
      diminished and was accompanied by a significant improvement in sperm motility. A
      significant increase of morphologically normal sperm cells was observed at 8
      weeks of treatment, and these changes remained until at least 4 weeks after the
      end of treatment.

PMID- 16412768
TI  - Postoperative endocrine alterations and clinical outcome of infertile women with
      polycystic ovary syndrome after transvaginal hydrolaparoscopic ovarian drilling.
AB  - Transvaginal hydrolaparoscopic ovarian drilling (THLOD) appears to be an
      effective minimally invasive procedure to induce ovulation in women with
      polycystic ovary syndrome (PCOS). Postoperative endocrinological alterations
      following THLOD show significant decrease of serum LH and testosterone
      concentrations.

PMID- 16412769
TI  - Gonadotropin-releasing hormone (GnRH) antagonist plus recombinant luteinizing
      hormone vs. a standard GnRH agonist short protocol in patients at risk for poor
      ovarian response.
AB  - Various studies have compared the efficacy of GnRH agonists (GnRH-a) and
      antagonists (GnRH-ant) for controlled ovarian stimulation (COS) in women
      undergoing IVF. Nevertheless, few data are available about the use of GnRH-ant in
      poor responders. Here, a flexible protocol providing a gradual increase in the
      dose of GnRH-ant in association with recombinant LH (rec-LH) administration is
      compared with the standard GnRH-a flare-up protocol in 133 women at risk for poor
      ovarian response. The mean number of metaphase 2 oocytes (primary end point) was
      significantly higher in the antagonist group (5.73 +/- 3.57 vs. 4.64 +/- 2.23,
      respectively; P<.05).

PMID- 16412770
TI  - Treatment with gonadotropin-releasing hormone (GnRH) antagonists in women
      suppressed with GnRH agonist may avoid cycle cancellation in patients at risk for
      ovarian hyperstimulation syndrome.
AB  - Forty-seven patients at high risk for ovarian hyperstimulation syndrome because
      of markedly elevated serum E2 levels on either long-luteal or microdose flare
      leuprolide acetate regimens were treated with ganirelix acetate. Despite being
      pretreated with GnRH agonist and without withholding gonadotropins, serum E2
      decreased by 49.5% and 41.0% of pretreatment values (long luteal and microdose
      flare, respectively) after initiation of ganirelix, and 68.1% of the patients
      became pregnant.

PMID- 16412771
TI  - Mouse ascites Golgi mucin expression abnormalities in natural cycle endometrial
      biopsies predict subsequent in vitro fertilization-embryo transfer (IVF-ET)
      failure in patients with previous IVF-ET failures.
AB  - We performed a double-blinded retrospective cohort study to determine whether
      endometrial expression of mouse ascites Golgi mucin in a natural, unmedicated
      cycle predicts subsequent IVF-ET outcome among women with prior IVF-ET failure
      and poor pre-embryo quality. We found a statistically significant decrease in
      clinical pregnancy rate among women with abnormal mouse ascites Golgi expression,
      a test which was found to have high positive predictive value for failed IVF-ET.

PMID- 16412772
TI  - The forgotten variable: impact of luteinizing hormone on the prediction of
      ovarian reserve.
AB  - The impact of basal LH levels in the prediction of ovarian function in women
      initiating fertility treatment remains controversial. The present study
      demonstrates high-normal basal LH levels as a good, and low-normal basal LH
      levels as a negative prognostic sign for oocyte yield in regular-cycling women
      with borderline basal FSH levels (10.1-15 mU/mL).

PMID- 16412773
TI  - Variations in tubal configuration in endometriosis?

PMID- 16412776
TI  - Assessment of measurement validity.

PMID- 16412778
TI  - Epigenetics and assisted reproductive technology.

PMID- 16412779
TI  - Always an important question: the experimental unit--"patients or cycles"?

PMID- 16412780
TI  - Always an important question: the experimental unit--"patients of cycles?".

PMID- 16412781
TI  - Always an important question: the experimental unit--"patients or cycles"?

PMID- 16412783
TI  - Graft-versus-host disease in the 21st century: new perspectives on an old
      problem.

PMID- 16412784
TI  - Pathophysiology of graft-versus-host disease.
AB  - Complications of allogeneic hematopoietic stem cell transplantation (HSCT) remain
      barriers to its wider application for a variety of diseases. Graft-versus-host
      disease (GVHD) is the major cause of morbidity and mortality following allogeneic
      HSCT. GVHD can be considered an exaggerated, undesirable manifestation of a
      normal inflammatory mechanism, in which donor lymphocytes encounter foreign
      antigens in a milieu that fosters inflammation. Recent advances in the study of
      cytokine networks, chemokine gradients, and the direct mediators of cellular
      cytotoxicity have led to improved understanding of this complex syndrome. The
      pathophysiology of acute GVHD can be considered as a three-step process in which
      the innate and adaptive immune systems interact: (1) tissue damage to the
      recipient by the radiation/chemotherapy pretransplant conditioning regimen; (2)
      donor T-cell activation and clonal expansion; and (3) cellular and inflammatory
      factors. Here we review the immunologic interactions that cause clinical GVHD and
      discuss the risk factors and prophylactic strategies for acute GVHD according to
      this model.

PMID- 16412785
TI  - Genetics of risk factors for graft-versus-host disease.
AB  - Modern understanding of the genetic basis of graft-versus-host disease (GVHD) in
      allogeneic hematopoietic stem cell transplantation (HSCT) involves knowledge of
      human leukocyte antigen (HLA), killer immunoglobulin-like receptors (KIR),
      cytokine genes, and their interactions. Insights into the immunogenetic basis of
      GVHD come from long-standing clinical experience in the use of myeloablative
      conditioning regimens and donor bone marrow as the grafting source. Under these
      circumstances, donor T-cell recognition of host HLA can cause GVHD. The recent
      elucidation of HLA class I as ligands for natural killer (NK) cell inhibitory KIR
      demonstrates that GVHD is the result of a complex interplay between the innate
      and adaptive immune responses. The extent to which T cells and NK cells
      contribute to clinical GVHD is a function of the host post-conditioning
      environment, immunosuppressive treatments, and the content of the graft source.
      The contribution of donor and host genetic differences in cytokine genes in
      modulating risks of GVHD has recently been recognized.

PMID- 16412786
TI  - The clinical spectrum of acute graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD), initiated by the reaction of donor T
      lymphocytes against nonshared recipient antigens, typically leads to a clinical
      syndrome characterized by cutaneous eruptions and intestinal and hepatic
      dysfunction. These three organ systems are considered in the clinical grading of
      acute GVHD. However, other targets may be involved. With conventional transplant
      conditioning regimens and in vivo prophylaxis, GVHD becomes clinically manifest
      within 2 to 4 weeks. With reduced-intensity conditioning, the onset of acute GVHD
      may be delayed until 2 to 3 months after transplantation. Hyperacute GVHD may
      occur within a week of transplantation after severely human leukocyte antigen
      (HLA)-mismatched transplants or transplants without GVHD prophylaxis. There is no
      reliable laboratory test for acute GVHD, and the diagnosis is based on clinical
      assessment.

PMID- 16412787
TI  - Prophylaxis and treatment of acute graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD) remains a major obstacle to successful
      allogeneic hematopoietic stem cell transplantation (HSCT). The ability to prevent
      GVHD--the application of successful prophylaxis--is crucial as treatment when
      prophylaxis fails or remains suboptimal. A calcineurin inhibitor in combination
      with methotrexate is still the mainstream regimen for prophylaxis of GVHD.
      Despite a steady increase in the repertoire of available drugs, corticosteroids
      remain the first-line therapy for patients who fail prevention and develop GVHD.
      Pan T-cell depletion studies suggest that success in prophylaxis and treatment of
      GVHD will depend on whether GVHD can be prevented without losing anti-malignancy
      and anti-infectious effects. Better understanding of the allogeneic response that
      is responsible for GVHD will facilitate the development of such an approach.

PMID- 16412788
TI  - The lung as a target organ of graft-versus-host disease.
AB  - Despite significant advances in critical care and transplantation medicine, non
      infectious lung injury remains a major problem following allogeneic hematopoietic
      stem cell transplantation (HSCT) both in the immediate post-transplant period and
      in the months to years that follow. Historically, approximately 50% of all
      pneumonias seen after HSCT have been secondary to infection. Although non
      infectious lung injury occasionally occurs following autologous transplants, the
      allogeneic setting greatly exacerbates toxicity acutely and chronically.
      Pulmonary injury is associated with significant morbidity and mortality and
      responds poorly to standard therapies. Insights generated using animal models
      suggest that the immunologic mechanisms contributing to lung inflammation after
      HSCT may be similar to those responsible for graft-versus-host disease (GVHD).

PMID- 16412789
TI  - Graft-versus-host disease and graft-versus-leukemia after donor leukocyte
      infusion.
AB  - Although dramatically effective for relapsed chronic myelogenous leukemia (CML),
      successful donor leukocyte infusion (DLI) remains limited primarily by inadequate
      responses for patients with diseases other than CML and by toxicity related to
      graft-versus-host disease (GVHD). Acute GVHD grades 2 to 4 follows 34% to 47% of
      infusions and chronic GVHD occurs in 33% to 61% of cases. Strategies to reduce
      the incidence and severity of GVHD while preserving the graft-versus-leukemia
      (GVL) effect, such as low-dose DLI, depletion of GVHD effector cells, and tumor
      specific DLI, are reviewed.

PMID- 16412790
TI  - CD4+CD25+ regulatory T cells and graft-versus-host disease.
AB  - Peripheral suppression of autoreactive T cells by specialized T-cell populations
      is one of several mechanisms ensuring self-tolerance within the adaptive immune
      system. Thymus-derived CD4+CD25+ T cells expressing the transcriptional repressor
      FOXP3 mediate such immunoregulatory functions and are pivotal for the prevention
      of autoimmunity. As peripheral tolerance induction is a prerequisite for
      successful treatment outcome after allogeneic hematopoietic stem cell
      transplantation (HSCT), the role of CD4+CD25+ T cells in transplantation models
      and clinical trials is now under investigation in many laboratories. Here we
      summarize recent results regarding protection from graft-versus-host disease
      (GVHD) by adoptively transferred CD4+CD25+ T cells in mice and discuss early
      findings from clinical studies in HSCT.

PMID- 16412791
TI  - Diagnosis and treatment of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) is the major cause of non-relapse
      morbidity and mortality after hematopoietic stem cell transplant (HSCT). GVHD
      also is associated with a potent anti-leukemic effect. Chronic GVHD resembles
      autoimmune diseases and can likely affect any organ or tissue of the body. Skin,
      oral, liver, and lacrimal gland involvement are most common. The incidence and
      presentation have been in evolution as new stem cell sources and transplant
      approaches have been introduced. Although progress in the diagnosis and treatment
      of chronic GVHD has been limited for many years, there is renewed interest in
      this disorder. New prognostic scores and animal models of chronic GVHD have been
      developed. Large, multicenter phase III therapy and biology studies have been
      undertaken. The challenge for the future will be the discovery of targeted
      approaches that allow the anti-leukemic effect to be retained and for the
      reconstitution of normal immunity, thereby reducing infectious complications.

PMID- 16412793
TI  - Should we measure routinely the LDL peak particle size?
AB  - Low density lipoproteins (LDL) do not show in humans a normal distribution and
      comprise two different main fractions: large, buoyant (phenotype pattern A) and
      small, dense (phenotype pattern B) particles, that differ not only in size and
      density but also in physicochemical composition, metabolic behaviour and
      atherogenicity. The prevalence of small, dense LDL changes with age (30-35% in
      adult men, 5-10% in men <20 years and in pre-menopausal women, 15-25% in
      postmenopausal women) and is genetically influenced, with a heritability ranging
      from 35% to 45%. Small, dense LDL correlate negatively with plasma HDL levels and
      positively with plasma triglyceride levels and are associated with the metabolic
      syndrome and with increased risk for cardiovascular disease and diabetes
      mellitus. LDL size seems also to be an important predictor of cardiovascular
      events and progression of coronary artery disease and the predominance of small
      dense LDL has been accepted as an emerging cardiovascular risk factor by the
      National Cholesterol Education Program Adult Treatment Panel III. In addition,
      patients with acute myocardial infarction show an early reduction of LDL size,
      which persists during hospitalization and seems to precede all other plasma
      lipoprotein modifications. However, it is still on debate whether to measure the
      LDL size routinely and in which categories of patients. Since the therapeutic
      modulation of small, dense LDL particles is of great benefit in reducing the
      atherosclerotic risk, the LDL size measurement should be extended to patients at
      high risk of coronary artery disease as much as possible.

PMID- 16412794
TI  - Impact of redefining acute myocardial infarction on incidence, management and
      reimbursement rate of acute coronary syndromes.
AB  - BACKGROUND: Although redefinition for acute myocardial infarction (AMI) has been
      proposed few years ago, to date it has not been universally adopted by many
      institutions. The purpose of this study is to evaluate the diagnostic, prognostic
      and economical impact of the new diagnostic criteria for AMI. METHODS: Patients
      consecutively admitted to the emergency department with suspected acute coronary
      syndromes were enrolled in this study. Troponin T (cTnT) was measured in samples
      collected for routine CK-MB analyses and results were not available to
      physicians. Patients without AMI by traditional criteria and cTnT > or = 0.035
      ng/mL were coded as redefined AMI. Clinical outcomes were hospital death, major
      cardiac events and revascularization procedures. In-hospital management and
      reimbursement rates were also analyzed. RESULTS: Among 363 patients, 59 (16%)
      patients had AMI by conventional criteria, whereas additional 75 (21%) had
      redefined AMI, an increase of 127% in the incidence. Patients with redefined AMI
      were significantly older, more frequently male, with atypical chest pain and more
      risk factors. In multivariate analysis, redefined AMI was associated with 3.1
      fold higher hospital death (95% CI: 0.6-14) and a 5.6 fold more cardiac events
      (95% CI: 2.1-15) compared to those without AMI. From hospital perspective, based
      on DRGs payment system, adoption of AMI redefinition would increase 12% the
      reimbursement rate [3552 Int dollars per 100 patients evaluated]. CONCLUSIONS:
      The redefined criteria result in a substantial increase in AMI cases, and allow
      identification of high-risk patients. Efforts should be made to reinforce the
      adoption of AMI redefinition, which may result in more qualified and efficient
      management of ACS.

PMID- 16412795
TI  - Trajectory of prehospital delay in patients with acute myocardial infarction in
      the Japanese health care system.
AB  - OBJECTIVE: The purpose of this study was to understand the trajectory of
      prehospital delay in patients with acute myocardial infarction (AMI) in the
      Japanese health care system, which offers patients a choice between seeking
      treatment in a neighborhood clinic/small hospital (clinic group) or a large
      hospital with comprehensive cardiac services, including a cardiac catheterization
      laboratory (hospital group). METHODS: In this cross sectional study, 155
      consecutive patients admitted with AMI to one of 5 urban hospitals in Japan were
      interviewed within 7 days after admission. RESULTS: The median total prehospital
      delay time in the clinic group (n=84) was significantly longer than the hospital
      group (n=71) (6 h and 48 min vs 2 h and 9 min, p<.001). Patients with severe
      chest pain were significantly less likely to seek treatment at a clinic/small
      hospital than at a large hospital compared to patients with mild or moderate
      symptoms (OR 0.85, 95% CI: 0.75, 0.97). Patients who did not interpret their
      symptoms as cardiac in origin were significantly more likely to seek treatment at
      a clinic/small hospital than at a large hospital compared to patients who
      interpreted their symptoms as cardiac in origin (OR 3.32, 95% CI: 1.56, 7.10).
      After controlling for demographic and medical history, patients in the clinic
      group were 3.69 times (95% CI: 1.28, 10.66) less likely to receive any
      reperfusion therapy compared to patients in the hospital group. CONCLUSIONS:
      Findings support the need for public education in Japan that focuses on the
      appropriate response to AMI symptoms. Moreover, regional AMI networks need to be
      instituted to provide for early transfer for PCI from clinic/small hospitals to
      tertiary centers.

PMID- 16412796
TI  - Estrogen therapy effects on different vasoactive factors in recent postmenopausal
      healthy women.
AB  - BACKGROUND: To evaluate whether the route of estrogen therapy (ET) may affect the
      levels of different vasoactive factors in healthy recent post-menopausal women.
      METHODS: We conducted a cross-over study in 20 healthy nonsmoking women in recent
      postmenopause (1.8+/-0.1 years). Women received either 1-month oral-ET (O-ET, 2
      mg oral micronized 17beta estradiol daily) or transdermal-ET regimen (T-ET,
      17beta estradiol 1.5 mg gel daily) with a 1-month wash-out interval. Blood
      pressure, plasma levels of endothelin-1 (ET), 6-ketoPGF1a (6-ketoPG, prostacyclin
      metabolite), nitrite/nitrate (NOx), epinephrine (E) and norepinephrine (NE) and
      lipid profile were measured at baseline and after each treatment. RESULTS: Both
      regimens significantly reduced E (p<0.01) and NE levels (p<0.05). O-ET reduced
      low-density lipoproteins (LDL) levels (p<0.05) and increased NOx values (p<0.01).
      Neither regimen caused significant changes of ET or 6-ketoPG. CONCLUSIONS: Our
      results, obtained in healthy women in recent menopause, indicate that the ratio
      between vasodilator (NOx and prostacyclin) and vasoconstrictor (ET)
      bioavailability shifted towards the previous ones after O-ET, while it remained
      unchanged after T-ET; moreover, catecholamines levels were reduced by both
      treatments already from 1 month of therapy. These changes might represent very
      early beneficial effects evoked by ET on the cardiovascular system.

PMID- 16412797
TI  - Ergonovine test in angina with normal coronary arteries. Is it worth doing it?
AB  - BACKGROUND: Patients with angina and normal coronary arteries are often
      misdiagnosed with having non-cardiac pain. Although vasospasm is a well-known
      entity, spasm provocation is not routinely done in the majority of hospitals at
      present. MATERIALS AND METHODS: One hundred and sixty two consecutive patients
      with thoracic pain and normal coronary arteries were retrospectively studied. The
      characteristics of pain were analysed. One hundred and sixty one non-invasive
      tests (with and without imaging) were done to 126 patients before angiography.
      Increasing doses of ergonovine (from 1 to 30 microg) were injected into the
      coronary arteries to provoke coronary spasm. The correlation between ergonovine
      induced spasm and non-invasive tests was studied. RESULTS: Oppressive thoracic
      pain suggestive of angina was present in 144 patients. It occurred at rest in 59
      patients, only at night in 14, with effort in 40, and it was mixed in 31. Non
      oppressive atypical pain was reported by 18 patients. Non-invasive tests were 94
      positive, 60 negative and 7 non-diagnostic. Ergonovine test elicited coronary
      spasm in 85 patients (52.5%). No significant correlation was found between the
      positivity of a non-invasive test and ergonovine-induced spasm. CONCLUSIONS: More
      than half of the patients with angina and normal coronary arteries can be
      diagnosed with vasospastic angina if ergonovine test is performed. Even patients
      with a negative non-invasive test maybe sent to coronary angiography when
      vasospastic angina is suspected, in order to have an accurate diagnosis.

PMID- 16412798
TI  - Transcatheter device closure of atrial septal defects in the elderly: technical
      considerations and short-term outcomes.
AB  - BACKGROUND: Device closure of an atrial septal defect (ASD) results in symptom
      reduction, right heart remodelling and lower pulmonary artery pressures. However
      it is unclear if there is a chronological limit to these benefits and whether
      device closure is safe in elderly subjects. The aim of this study was, therefore,
      to assess the safety and efficacy of device closure in patients >60 years.
      METHODS: Retrospective study of Amplatzer Septal Occluder device closures from a
      single institution (May 1999-August 2002). RESULTS: Fifty subjects aged >60 years
      (range 60-85 years) had ASD device closure (27% of the total cohort). Defect size
      and shunt size were similar for both younger and older groups (2.2:1 in both
      groups, p=0.9) as were procedural duration, fluoroscopy time and device size
      deployed. Baseline right ventricular (RV) systolic pressure ((younger vs. older)
      39 vs. 49 mmHg, p<0.001) and right ventricular size (45 vs. 51 mm, p<0.001) were
      greater in the older group. Following closure RV systolic pressure (49 vs. 45
      mmHg, p<0.01) and RV size (51 vs. 44 mm, p=0.01) decreased in the older group.
      CONCLUSION: Device closure of an ASD can be performed safely in older patients.
      The right heart shows signs of remodelling even in elderly subjects.

PMID- 16412799
TI  - Effect of heart failure on skeletal muscle myofibrillar protein content, isoform
      expression and calcium sensitivity.
AB  - BACKGROUND: Alterations in skeletal muscle with heart failure contribute to
      exercise intolerance and physical disability. The majority of studies to date
      have examined abnormalities in skeletal muscle oxidative capacity and
      mitochondrial function. In contrast, less information is available regarding the
      effect of heart failure on myofibrillar protein metabolism and function. To
      address this issue, we examined the effect of heart failure on skeletal muscle
      myofibrillar protein content, isoform distribution and Ca2+ sensitivity. METHODS:
      We measured skeletal muscle myosin heavy chain (MHC) and actin protein content
      and MHC isoform distribution in soleus (SOL), extensor digitorum longus (EDL),
      plantaris (PL) and diaphragm (DIA) muscles and myofibrillar Ca2+ sensitivity in
      EDL muscles from Dahl salt-sensitive rats with (high-salt fed: HS; n=10) or
      without heart failure (low-salt fed: LS; n=8) and assessed the relationship of
      these variables to markers of disease severity. RESULTS: No differences in muscle
      mass were found. Similarly, no differences in MHC (mean+/-SE; SOL: 1353+/-29 vs.
      1247+/-52; EDL: 1471+/-31 vs. 1441+/-31; PL: 1207+/-66 vs. 1286+/-36; DIA: 1166+/
      42 vs. 1239+/-26 AU/microg protein) or actin (EDL: 348+/-13 vs. 358+/-19; PL:
      245+/-20 vs. 242+/-9; DIA: 383+/-9 vs. 376+/-17 AU/microg protein) protein
      content or the actin-to-MHC ratio were observed, with the exception of lower
      (P<0.01) actin content in the soleus of LS rats (352+/-7 vs. 310+/-8 AU/microg
      protein). MHC isoform expression (I, IIa, IIx, IIb) did not differ between groups
      in SOL (I: 89+/-1% vs. 85+/-2%; IIa: 11+/-1% vs. 15+/-2%), EDL (IIx: 43+/-10% vs.
      38+/-10%; IIb: 57+/-10% vs. 62+/-10%), PL (I: 6+/-4% vs. 3+/-3%; IIa: 1+/-1% vs.
      1+/-1%; IIx: 31+/-3% vs. 26+/-4%; IIb: 62+/-5% vs. 71+/-6%) or DIA (I: 43+/-6%
      vs. 36+/-6 %; IIa: 9+/-1% vs. 7+/-1%; IIx: 47+/-6% vs. 56+/-7%; IIb: 2+/-1% vs.
      1+/-0.5%) muscles. Moreover, heart failure did not affect the Ca2+ sensitivity
      (i.e., pCa50) of extensor digitorum longus myofilaments (5.68+/-0.11 vs. 5.65+/
      0.09). Finally, MHC and actin content, MHC isoform distribution and myofibrillar
      Ca2+ sensitivity were not related to markers of disease severity. CONCLUSIONS:
      Our results show that this animal model of heart failure is not characterized by
      alterations in the quantity or isoform distribution of key skeletal muscle
      myofibrillar proteins or the Ca2+ sensitivity of isometric force production.
      These findings suggest that alterations in skeletal muscle myofibrillar protein
      metabolism do not develop in parallel with myocardial failure in the Dahl salt
      sensitive rat.

PMID- 16412800
TI  - Does atrial fibrillation in very elderly patients with chronic systolic heart
      failure limit the use of carvedilol?
AB  - BACKGROUND AND AIMS: It is well known that beta-blockers are useful in patients
      with chronic heart failure (CHF). These favourable effects have recently been
      observed even in elderly CHF patients. Objectives of the present study were to
      evaluate the feasibility, tolerability and safety of carvedilol therapy in a
      cohort of patients > 70 years of age with CHF and left ventricular ejection
      fraction < 40% with chronic atrial fibrillation. For this purpose, we designed an
      observational, 12-month prospective study. RESULTS: Among 240 patients who were
      referred to our centers and met inclusion criteria, 64 had chronic atrial
      fibrillation (27%). Thirty-nine out of these 64 subjects (61%) were treated with
      carvedilol, while 25 patients (39%) had contraindications to such treatment. In
      the cohort of 176 patients with stable sinus rhythm (control group), carvedilol
      could be administered in 121 patients (69%), while it was not given in 55 (31%,
      p=ns). Airways disease was the main reason for exclusion from carvedilol in this
      setting of patients. No difference in 1-year tolerability of study drug was
      observed among patients with chronic atrial fibrillation (29 of 33
      patients=87.9%) and stable sinus rhythm (95 of 102=93.1%). Adverse events leading
      to the discontinuation of carvedilol in these two populations were rare and never
      resulted in any disability, death or were life-threatening. CONCLUSION: In over
      70 patients with systolic CHF, chronic atrial fibrillation does not limit the
      possibility of testing beta-blocker therapy. Carvedilol was equally tolerated and
      safe in patients with atrial fibrillation and sinus rhythm.

PMID- 16412801
TI  - Predictive value of asymptomatic cervical bruit for carotid artery disease in
      coronary artery surgery revisited.
AB  - OBJECTIVE: To investigate the predictive value of asymptomatic cervical bruit for
      detecting internal carotid artery disease in consecutive patients undergoing
      coronary artery bypass grafting (CABG). DESIGN: A prospective cohort study.
      SETTING: Tertiary referral university hospitals. PATIENTS: 153 consecutive
      patients (mean age 57 years) undergoing CABG, without previous history of
      cerebrovascular events. INTERVENTIONS: Patients underwent detailed pre-operative
      work-up, including coronary angiography and carotid artery duplex scanning.
      Internal carotid artery diameter stenosis was graded as A: normal; B: < 15%; C:
      15%-50%; D: 50-80%; D+: > 80-99% and E=complete occlusion. RESULTS: 72 patients
      (47.1%) (95% CI: 39%, 55%) had no evidence of internal carotid artery stenosis;
      81 (52.9%) (95% CI: 44.9%, 60.9%) had varying grades of disease, unilateral or
      bilateral. Cervical bruit was detected in 12/153 patients (7.8%) (95% CI: 3.5%,
      12.1%) of whom all but one (0.7%) had varying grades of internal carotid artery
      disease; of these, 4 patients had bilateral cervical bruit (2.6%) (95% CI: 0.06%,
      5.2%). The sensitivity, specificity, positive and negative predictive values and
      overall accuracy of cervical bruit for detection of > or = 50% internal carotid
      artery stenosis were 23.5%, 95.8%, 25%, 95.5% and 91.8%, respectively. The
      relative risk of > or = 50% stenosis ipsilateral to cervical bruit in 306 sides
      was 5.58 (95% CI: 2.0, 15.0) and the odds ratio 7.1 (95% CI: 2.0, 25.0).
      CONCLUSIONS: Asymptomatic cervical bruit proved a highly specific clinical sign
      for detection of internal carotid artery stenosis, whether haemodynamically
      significant (> or = 50%) or otherwise, in patients undergoing myocardial
      revascularisation. This was matched by a high negative predictive value and
      overall accuracy for flow limiting atheroma (> or = 50% stenosis). Yet, steering
      carotid investigations on the basis of cervical bruit alone would result in > or
      = 80% internal carotid artery stenosis remaining undetected in 3% of overall
      patients, in whom cervical bruit is absent.

PMID- 16412802
TI  - Chronic sinusitis and arterial hypertension in a national population health
      survey.
AB  - BACKGROUND: To determine if sinusitis is associated with arterial hypertension in
      the Canadian population. METHODS: Complex survey design incorporating
      stratification, multiple stages of selection, and unequal probabilities of
      selection of respondents. Cross-sectional data from 52,992 subjects (25,324 males
      and 27,668 females) 20-64 years of age who participated in the second cycle of
      the National Population Health Survey (NPHS), conducted in 1996-1997. All these
      individuals were asked if they had certain chronic health conditions, that had
      lasted or were expected to last 6 months or more, including sinusitis and high
      blood pressure. RESULTS: Overall, males with sinusitis were just over 2% more
      likely to have hypertension (9.3% vs. 7.1%) whereas the difference was 4% for
      women (11.8% vs. 7.6%). Adjusted for age, region, habitation, immigrant status,
      household size, number of bedrooms, income adequacy, education level, smoking
      status, alcohol consumption, regular exercise and body mass index, the adjusted
      odds ratio for females was 1.42 (95% CI 1.04, 1.95). CONCLUSIONS: Reported
      sinusitis is associated with hypertension but only in women. Mechanisms linking
      upper respiratory disorders to hypertension merit investigation.

PMID- 16412803
TI  - Sudden death is less common than might be expected in underprivileged ethnic
      minorities at high cardiovascular risk.
AB  - Sudden cardiac death can be the presenting feature of coronary disease. Limited
      epidemiological studies from the US suggest an increased prevalence of sudden
      death in the African-American community. There are no reports in UK minority
      communities. We present sudden death data from an area with a high density of
      underprivileged ethnic minority groups. METHODS: Ambulance data forms and
      accident and emergency records of all sudden unexpected deaths bought to City
      Hospital Birmingham in 2002 were extracted by retrospective review. The clinical
      characteristics and timing of the events were defined and analysed on the basis
      of the ethnic origins of the victims. RESULTS: The prevalence of sudden death
      amongst Caucasians was substantially greater than among minorities. Both Indo
      Asians and Afro-Caribbean groups had a lower than expected sudden death rate.
      Caucasian patients more commonly demonstrated a ventricular fibrillation (VF)
      rhythm at presentation while Indo-Asians and Afro-Caribbean's demonstrated a non
      VF rhythm (asystole and pulseless electrical activity (PEA). Collapse with
      syncope was more common in Afro-Caribbean subjects while Indo-Asian subjects more
      often arrested in transit. There were no differences in call or transfer times.
      CONCLUSIONS: Despite a well-described pattern of more aggressive coronary
      disease, particularly noted in South Asian communities in the UK, the sudden
      death rate are not increased and may be decreased. This implies a potentially
      separate mechanism or a confounding cultural influence in these events.

PMID- 16412804
TI  - Downstream administration of a high-dose tirofiban bolus in high-risk patients
      with unstable angina undergoing early percutaneous coronary intervention.
AB  - BACKGROUND: The best treatment option for high-risk patients with unstable
      coronary syndrome is an early invasive strategy accompanied by intensive anti
      platelet therapy. We tested the effect on clinical outcome of early coronary
      angioplasty using a high-dose bolus of tirofiban in patients with non-ST segment
      elevation acute coronary syndrome. METHODS: One hundred and forty consecutive
      patients with unstable coronary syndrome who underwent an immediate percutaneous
      coronary intervention with the administration of a high (25 microg/kg) dose bolus
      of tirofiban followed by an 18-h infusion of 0.15 microg kg(-1) min(-1) were
      compared with a matched control group of 162 patients treated with abciximab. The
      primary endpoint of the study was the 30-day incidence of major adverse cardiac
      events; the secondary endpoints were the incidence of major and minor bleeding.
      RESULTS: The time from admission to PCI was slightly shorter in the tirofiban
      group (3.9+/-4.8 vs. 4.5+/-4.4 h; P=0.26). The 30-day rate of major adverse
      cardiac events was similar in the two groups (6% with tirofiban and 8.6% with
      abciximab: OR=1.37, 95% CI=0.58-3.29, P=0.52). No major bleeding episodes were
      observed; the incidence of minor bleeding was 3.6% in the tirofiban group and
      2.5% in the abciximab group (OR=0.68, 95% CI=0.18-2.59, P=0.74). CONCLUSIONS: In
      this preliminary study, the beneficial effect of the administration of a high
      dose tirofiban bolus on 30-day clinical outcomes was similar to that of abciximab
      in high-risk patients with unstable angina undergoing immediate percutaneous
      coronary intervention. The results of this therapeutic strategy should be tested
      in a larger randomised study.

PMID- 16412805
TI  - Determinants of model of renarrowing after beta radiation for in-stent
      restenosis.
AB  - It is unknown whether model of renarrowing after beta-radiation for in-stent
      restenosis (ISR) is influenced by the type of geographic miss (GM). METHODS: In
      166 ISR treated with Galileo, serial quantitative coronary angiographic analysis
      was done. Minimal lumen diameters and lengths were measured for (1) stent, (2)
      peri-stent subsegments subjected to angioplasty with/without irradiation, and (3)
      irradiation margins. GM was defined as: (Type 1) edge injury within the 32P
      source dose fall-off: 2.0 mm inside and outside the source end marker or (Type 2)
      overt, nonirradiated injury: beyond the outer 2.0-mm long dose fall-off zone.
      RESULTS: Restenosis rate was 28.3% at 8.9+/-4.5 months with 60% located
      exclusively outside the stent. Type 1 GM was present in 24.7% of proximal edges,
      whereas Type 2 in 18.1%. Respective percentages for distal edges were 23.5% and
      15.7%. Regardless of presence and type of GM, significant late lumen loss
      occurred only outside the stent. However, the biggest late lumen loss at the
      proximal edge was induced by the Type 1 GM (0.65+/-0.79, p<0.001), while proximal
      Type 2 GM was not associated with edge renarrowing (-0.04+/-0.48, p=NS). Both
      reference lumen diameter and proximal Type 1 GM influenced restenosis
      independently (OR 0.47; 95%CI 0.24-0.90; p=0.023 and OR 2.46; 95%CI 1.12-5.40;
      p=0.025). CONCLUSIONS: Regardless of presence and type of geographic miss, late
      lumen loss after beta-radiation occurs only outside the stent. However, injury
      within the proximal 32P dose fall-off but not overt edge injury is associated
      with the biggest late lumen loss at the respective edge, triggering recurrent
      restenosis.

PMID- 16412806
TI  - Effect of estradiol 17beta upon coronary artery vasoconstrictor response to
      methylergometrine maleate in female menopausal patients.
AB  - BACKGROUND: Estrogens produce several beneficial effects upon the cardiovascular
      system. Amongst these, an endothelium-independent effect has been convincingly
      demonstrated only in vitro, while there is no evidence for such an effect in
      vivo. The aim of the present study was to evaluate the effect of acute
      administration of estradiol 17beta upon coronary artery reactivity to
      methylergometrine in 16 menopausal patients with coronary artery disease.
      METHODS: Sixteen menopausal patients underwent coronary angiography at rest and
      after incremental doses of methylergometrine (intracoronary 2, 10, 30 microg)
      before and 20 min after either intracoronary estradiol 17beta (20 ng/mL at 1
      mL/min for 20 min; 8 patients) or placebo (Dextrose 5%, 1 mL/min; 8 patients).
      RESULTS AND CONCLUSIONS: No significant differences were observed in baseline
      coronary artery diameter or area between the 2 groups. No significant differences
      in the degree of coronary artery constriction were observed after either
      estradiol 17beta or placebo at submaximal doses of methylergometrine. However,
      the degree of coronary artery constriction after maximal doses of
      methylergometrine was significantly attenuated by estradiol 17beta compared to
      placebo (change in diameter: -0.9+/-4.5% vs. -19+/-6%, p<0.001; change in area: 
      3.2+/-9% vs. -32.2+/-10%, p<0.001). Estradiol 17beta reduces coronary artery
      constriction following methylergometrine administration in menopausal patients
      with coronary artery disease. This effect may be related to the calcium
      antagonist properties of the ovarian hormone.

PMID- 16412807
TI  - Resting ST-segment depression predicts exercise-induced subendocardial ischemia
      in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes display
      characteristic electrocardiographic (ECG) findings at rest and develop
      subendocardial ischemia during exercise in the absence of coronary lesions.
      However, their relationship has not yet been fully clarified. METHODS: Exercise
      Tc-99m-tetrofosmin myocardial scintigraphy was performed in 48 patients with non
      obstructive HCM. We quantified transient left ventricular cavity dilation (LVCD)
      on exercise scintigrams, a parameter of subendocardial ischemia, and correlated
      the results with the ECG findings at rest and during exercise. RESULTS: Transient
      LVCD occurred during exercise in 17 (35%) patients with HCM. Hemodynamic
      parameters during exercise did not differ between HCM patients with and without
      transient LVCD. Multiple logistic regression analysis showed that transient LVCD
      was significantly associated with ST-segment depression at rest (chi2=5.00, odds
      ratio=5.70, 95% confidence intervals 1.24-26.18, P=0.025) and a greater total
      number of leads with resting ST-segment depression (chi2=6.38, odds ratio=1.60,
      95% confidence intervals 1.12-2.42, P=0.012). The degree of LVCD was correlated
      with the total number of leads with ST-segment depression at rest (P=0.002); the
      optimal cutoff for the diagnosis of transient LVCD was 3 with a sensitivity of
      65%, a specificity of 90%, and an accuracy of 81%. CONCLUSIONS: In patients with
      HCM, ST-segment depression at rest was accompanied by exercise-induced
      subendocardial perfusion abnormality as detected by myocardial scintigraphy. ST
      segment depression at rest suggests that the subendocardium is predisposed to
      exertional ischemia.

PMID- 16412808
TI  - Should patients with benign prostatic hypertrophy stop taking doxazosin in the
      light of the ALLHAT study?

PMID- 16412809
TI  - An aneurysm of posterior mitral valve mimicking a huge vegetation.

PMID- 16412810
TI  - Pseudo tricuspid regurgitation: unusual etiology of a pulsating liver.

PMID- 16412811
TI  - Seasonal variation in morbidity and mortality related to atrial fibrillation-
      could thyroid function contribute?

PMID- 16412812
TI  - Is left ventricular diastolic function an independent marker of prognosis after
      acute myocardial infarction?

PMID- 16412813
TI  - A mysterious journey of a cardiac pacemaker.
AB  - A permanent bipolar cardiac pacemaker was inserted in the abdomen of a child with
      Down's syndrome, due to complete heart block following repair of atrioventricular
      septal defect. This report describes an unusual and unreported complication of
      the pacemaker getting extruded through the rectum without dysfunction.
      Implications for early diagnosis and appropriate management and steps to prevent
      such episodes in future are discussed.

PMID- 16412814
TI  - Coronary heart disease in south Asia: need to redefine risk.
AB  - South Asian population has a high incidence of coronary artery disease. There are
      a number of risk factors that are almost unique to the south Asians. The
      classical risk factors do not account for such high rates of CHD as are present
      in south Asia. We have discussed some important aspects of CHD that can help in
      improving prevention in south Asia.

PMID- 16412815
TI  - Interesting case: monostotic fibrous dysplasia of the articular eminence of
      zygomatic bone.

PMID- 16412816
TI  - Candidate risk factors for cardiovascular disease in CKD.

PMID- 16412817
TI  - Causes of hyperhomocysteinemia in patients with chronic kidney diseases.
AB  - Plasma homocysteine (Hcy) levels are increased significantly in patients with
      moderate renal failure and increase markedly in patients with end-stage renal
      disease. An increase in plasma Hcy level theoretically could be caused by an
      increased production rate (ie, transmethylation), a decreased rate of removal by
      transsulfuration or remethylation, or a decrease in the excretion of Hcy. Current
      evidence indicates that the major mechanism for hyperhomocysteinemia in renal
      failure is a decrease in Hcy removal from the body. However, it is debated
      whether this effect is the result of a decrease in the renal metabolic clearance
      or a result of extrarenal metabolic changes. The human kidney plays a major role
      in the removal of several aminothiols or Hcy-related compounds from the
      circulation (eg, cysteine-glycine, glutathione, AdoMet, and AdoHcy). However, the
      glomerular filtration of Hcy seems to be restricted because of protein binding.
      Besides glomerular filtration, the normal kidney can remove Hcy by plasma flow
      and peritubular uptake. Although in the low normal range in absolute terms, the
      flow through the transsulfuration pathway is reduced if related to Hcy levels in
      uremia; in addition, the remethylation pathway also is impaired. Besides the
      potential effect of the reduced renal mass on Hcy removal, available evidence
      suggests the occurrence of a generalized down-regulation of the methionine cycle
      and catabolism in uremia. AdoHcy, sulfate, and dimethylglycine currently are
      being investigated as retained solutes that can inhibit 1 or more pathways of Hcy
      metabolism. In addition, the high Hcy levels decrease in malnourished end-stage
      renal disease patients and change according to nutrient intake and several other
      nutritional parameters, indicating that circulating Hcy levels become an
      expression of nutritional status.

PMID- 16412818
TI  - Genetic aspects of hyperhomocysteinemia in chronic kidney disease.
AB  - Patients with chronic kidney disease who are on dialysis or with a kidney
      transplant have higher total plasma homocysteine concentrations than individuals
      who are free from kidney disease. Several single-nucleotide polymorphisms of
      genes encoding enzymes that are involved in homocysteine metabolism have been
      studied in these patients. These polymorphisms are located in genes encoding of
      5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase,
      methionine synthase, cystathionine beta-synthase, glutamate carboxy peptidase II,
      reduced folate carrier 1, and transcobalamin II. Among the single-nucleotide
      polymorphisms studied, only MTHFR 677C>T was associated consistently with total
      plasma homocysteine levels, but there currently is no evidence of any association
      between MTHFR 677C>T genotype and long-term outcomes.

PMID- 16412819
TI  - Hyperhomocysteinemia, malnutrition, and inflammation in ESRD patients.
AB  - Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general
      population, but in end-stage renal disease patients some studies show a reverse
      association, i.e. higher levels of homocysteine are associated with better
      clinical outcome. In this brief review, we review the evidence that malnutrition,
      hypoalbuminemia, inflammation and diabetes mellitus may lower circulating levels
      of homocysteine. As these factors are strong predictors of clinical outcome, this
      may explain why lower homocysteine levels in end-stage renal disease patients are
      associated with worse clinical outcome. We conclude that these factors need to be
      taken into account in multivariate models evaluating the impact of
      hyperhomocysteinemia as a risk factor in end-stage renal disease patients.

PMID- 16412820
TI  - Toxic effects of hyperhomocysteinemia in chronic renal failure and in uremia:
      cardiovascular and metabolic consequences.
AB  - Hyperhomocysteinemia, highly prevalent in well-nourished patients with chronic
      renal failure and in uremia, causes toxic effects that can be envisioned in terms
      of cardiovascular risk increase. However, its effects on cellular metabolism and
      on gene expression, not to mention receptor regulation, only recently are being
      evaluated. For example, it has been shown that hypomethylation induced by
      hyperhomocysteinemia can alter erythrocyte membrane protein repair and gene
      expression. In addition, increased plasma protein L-isoaspartyl content, related
      to hyperhomocysteinemia and uremic toxicity, determines specific effects on
      protein function, with a reduced binding of homocysteine to albumin. We propose
      that uremia is a state in which proteins present a widespread derangement of
      structure-function relationships.

PMID- 16412821
TI  - Therapy of hyperhomocysteinemia in chronic kidney disease.
AB  - Recent published evidence suggests that the correction of the multiple
      remethylation pathway abnormalities in chronic kidney disease (CKD), beyond
      folate-related disturbances, enhanced removal of uremic toxins and/or
      homocysteine (Hcy), and maneuvers aimed to displace Hcy from protein-binding
      sites, may represent valuable strategies to normalize total Hcy concentrations in
      CKD patients. The relevance of decreasing Hcy levels for cardiovascular disease
      in CKD patients should be shown definitively by the results of ongoing randomized
      trials.

PMID- 16412822
TI  - Effect of different hemodialysis regimens on genomic damage in end-stage renal
      failure.
AB  - Patients with end-stage renal disease display enhanced genomic damage that may
      have pathophysiologic relevance for cancer development and cardiovascular
      complications. We investigated to what extent the genomic damage in peripheral
      blood lymphocytes can be modulated #1: by initiation of standard hemodialysis
      (SHD) in formerly conservatively treated end-stage renal disease patients, #2: by
      a switch from SHD to hemodiafiltration, and #3: daily dialysis (DHD). Genomic
      damage was evaluated by the micronuclei (MN) frequency test and the comet assay
      (CA). In a prospective study we found that initiation of SHD did not induce
      significant changes of genomic damage in peripheral blood lymphocytes whereas the
      change to hemodiafiltration improved the percentage of DNA in the tail as
      measured by CA without modulating the MN frequency. In a cross-sectional
      investigation the degree of genomic damage as evaluated by MN frequency was
      significantly lower in a patient group treated by DHD as compared with a group
      treated by SHD. In the DHD patients there also was a significant decrease of the
      plasma concentrations of urea and the advanced glycation end products imidazolone
      A, carboxymethyllysine, and of advanced glycation end product-associated
      fluorescence.

PMID- 16412823
TI  - Vascular calcification in uremic conditions: new insights into pathogenesis.
AB  - Chronic kidney disease (CKD) patients have an higher incidence of cardiovascular
      morbidity and mortality compared with the general population. In the past 10
      years, several studies pointed out that vascular calcification is a major cause
      of cardiovascular disease in the dialysis population. In CKD patients, high
      levels of serum phosphate and parathyroid hormone play a critical role in the
      pathogenesis of cardiovascular events. Calcium- and aluminum-free phosphate
      binders provide a new and effective therapeutic tool in preventing cardiovascular
      calcifications in CKD in animal models and in hemodialysis patients. Moreover,
      the pathogenesis of vascular and soft-tissue calcification, which traditionally
      has been associated with a passive calcium-phosphate deposition, certainly also
      is related to an active, cell-mediated process. In fact, some bone regulatory
      proteins seem to be able to induce or inhibit mineral deposition in the
      vasculature. In particular, bone matrix protein 7, alpha2-HS glycoprotein, and
      matrix GLA protein may be regulatory keys in preventing extraskeletal
      calcification in uremic conditions. This review presents the current
      understanding of the pathogenesis of vascular calcification in CKD patients,
      focusing on these 3 proteins and their protective action on extraskeletal
      calcification.

PMID- 16412824
TI  - Management of vascular calcification in CKD patients.
AB  - Vascular calcification is common in patients with chronic kidney disease (CKD)
      and it may affect almost every artery. It is associated with a significant
      increase in morbidity and mortality. Therefore, the detection, prevention and
      treatment of vascular calcification in CKD patients are critical for the overall
      approach for the management of these patients. Hyperphosphatemia, especially when
      the blood levels of serum phosphorus are above 5.5 mg/dl, plays a major role in
      the development of vascular calcification. Hyperphosphatemia induces vascular
      calcification by both passive and active processes. By increasing calcium
      phosphate product, hyperphosphatemia results in direct deposition of calcium
      salts in the arteries and in cardiac valves. The active process involves the
      uptake of phosphate by the smooth muscle cells of the arteries by a Na-P co
      transporter. This increase in cell phosphate then induces phenotypic changes of
      these cells, rendering them into osteoblasts which in turn, begin laying calcium
      salts in the arterial walls. Therefore, it is critical that the blood levels of
      serum phosphorus be maintained below 5.5 mg/dl in CKD patients. Inflammation and
      the production of C-reactive protein (CRP) and interleukin 6 are also risk
      factors for vascular injury and vascular calcification. In a study of 254
      dialysis patients with elevated blood levels of CRP (>1.0 mg/l) and 258 patients
      with CRP levels equal to or less than 1.0 mg/l, it was found that higher levels
      of CRP are significantly associated with the presence of both atheromatous and
      medial calcification of the aorta and hand arteries. Also, it was reported that a
      significant association between CRP levels and cardiac valves calcification in
      patients undergoing continuous ambulatory peritoneal dialysis. The reasons for
      the elevation in CRP in dialysis patients are not clear, but certainly, is more
      evident in those with obvious inflammatory processes. Therefore, any inflammation
      that is detected should be treated appropriately.

PMID- 16412825
TI  - Vascular erectile dysfunction in chronic renal failure.
AB  - The prevalence of erectile dysfunction (ED) has increased dramatically worldwide
      in parallel with the aging of the population. In 1995, ED was estimated to be
      present in more than 150 million men. Considering population aging in Western
      countries, estimates predict that more than 300 million men will be affected by
      ED by the year 2025. ED is a common and often distressing side effect of renal
      failure. It is present in 30% of patients with chronic renal failure and in 50%
      of patients undergoing dialysis treatment. Uremic men of different ages report a
      high variety of sexual problems including sexual hormonal pattern alterations,
      reduced or loss of libido, infertility, and impotence, thereby influencing their
      well-being. The pathogenetic mechanisms include physiologic, psychologic, and
      organic causes. Since the release of sildenafil citrate, the relationship between
      ED and the presence of cardiovascular disease (CVD) has been evaluated in several
      studies. Many of the risk factors for ED are the same as those for cardiac
      disease. CVD and ED are closely interrelated disease processes. Indeed, ED can be
      considered a symptom of vascular endothelial damage. Therefore, it can be
      expected that impotence will appear along with CVD, and the presence of ED
      suggests the existence of CVD. An accurate evaluation of the sexual histories of
      all men who present to internists, cardiologists, and also nephrologists for
      early detection of ED may allow for early diagnosis and management of CVD.

PMID- 16412826
TI  - Coagulation disorders in uremia.
AB  - In patients with end-stage renal disease on maintenance hemodialysis, coagulation
      abnormalities such as hypercoagulability and thrombosis are common. Thrombotic
      complications in uremic patients are frequent and include those occurring at the
      vascular access and in the coronary, cerebral, and retinal arteries. Data do not
      entirely clarify the mechanisms involved and further investigations are
      necessary. Here we show a summary of coagulation and fibrinolytic disorders in
      uremia and the novelties foreseen in molecular biology.

PMID- 16412827
TI  - Newer aspects of carnitine metabolism in uremia.
AB  - New knowledge on the physiologic role of L-carnitine and on the rationale of its
      use in patients on maintenance hemodialysis is provided. In particular, carnitine
      normalizes plasma and muscle carnitine levels and modifies both enzymatic pattern
      of muscle and morphology of single fibers, improving exercise tolerance. In
      addition, carnitine reduces erythropoietin requirements, the number of
      hypotensive episodes, improves ejection fraction, and decreases hospitalization.

PMID- 16412828
TI  - Depression in chronic kidney disease.
AB  - Depression is the most frequent psychiatric problem in patients with chronic
      renal disease and may predict patient outcome and mortality. Depression is linked
      to stressful life characterized by many losses and by dependence, which even may
      lead to suicide. Despite the large number of patients with chronic kidney disease
      and the economic burden they represent, only a few of these patients receive
      adequate diagnosis and therapy. Diagnostic and Statistical Manual of Mental
      Disorders-IV criteria for major depression may help in differentiating symptoms
      of uremia and depression. Pharmacotherapy is available and antidepressants
      (tricyclic antidepressants and selective serotonin re-uptake inhibitors) have
      been used successfully in various studies. Finally, there is a need for further
      well-designed, longitudinal, survival studies to clarify the relationship better
      between depression and the different stages of renal dysfunction.

PMID- 16412829
TI  - Insomnia and its comorbidities in chronic kidney disease.
AB  - Sleep disorders are among the factors that can reduce the quality of life in
      patients with chronic kidney disease. Chronic kidney disease patients could
      benefit from an accurate evaluation and treatment of insomnia because this sleep
      disorder is associated with a high persistence-relapse rate, poor physical
      health, and mental disease (anxiety, depression) both in terms of comorbidity and
      antecedent. A multilayer evaluation of insomnia is possible because of valid and
      reliable instruments (both objective and subjective). Furthermore, a rational
      etiologic model of insomnia allows better understanding and treatment as a result
      of effective cognitive-behavioral techniques.

PMID- 16412830
TI  - Sleeping disorders in early chronic kidney disease.
AB  - Studies in patients on maintenance hemodialysis have disclosed a high prevalence
      of sleeping disorders, which have been linked to various factors including blood
      urea levels, creatinine levels, parathyroid hormone levels, anemia, systolic and
      diastolic blood pressure, quality of life, disease intrusiveness, and
      comorbidities. In contrast, few studies have been performed in patients with
      chronic kidney disease (CKD), who represent the target of the present study. A
      group of 52 CKD patients were enrolled after characterization of their renal
      function. Comorbidities were evaluated by means of the Charlson Comorbidity
      Index. Sleep disorders were evaluated by means of the Sleep Disorder
      Questionnaire (SDQ), a 26-item questionnaire providing a hierarchic
      classification for relevant insomnia, relevant hypersomnia, subclinical
      disorders, or absence of sleep complaints. Results indicate that, in the early
      stages of CKD, at a time the comorbidity index is low, sleep disorders are
      present in 80.7% of patients. This finding, which needs to be confirmed in a
      larger cohort of patients, indicates that sleep disorders affect the lives of CKD
      patients as soon a diagnosis of disease potentially progressing to end-stage
      renal disease was made.

PMID- 16412831
TI  - Quality of life in patients with chronic kidney disease: focus on end-stage renal
      disease treated with hemodialysis.
AB  - The proper measures for assessing quality of life (QOL) in patients with chronic
      kidney disease (CKD) remain unclear. QOL measures are subjective or objective,
      functional or satisfaction-based, and generic or disease-specific. Treatment of
      end-stage renal disease with transplantation and treatment of anemia with
      erythropoietin in patients with CKD have been associated with dramatic
      improvements of QOL. Other factors such as age, ethnic or national background,
      stage of CKD, modality of dialytic therapy, exercise interventions, sleep
      disturbances, pain, erectile dysfunction, patient satisfaction with care,
      depressive affect, symptom burden, and perception of intrusiveness of illness may
      be associated with differential perception of QOL. Recent studies showed an
      association between assessment of QOL and morbidity and mortality in end-stage
      renal disease patients, suggesting the measures do matter. Further studies are
      necessary in patients with early stages of CKD and in children. QOL measures
      should include validated psychosocial measures of depressive affect, perception
      of burden of illness, and social support. The challenge for the next decade will
      be to continue to devise interventions that meaningfully increase the QOL of
      patients with CKD at all stages.

PMID- 16412832
TI  - Continuous monitoring of left ventricle function by VEST in hemodialyzed
      patients.
AB  - Cardiovascular disease is a major cause of morbidity and mortality in chronic
      kidney disease. Radionuclide-based methods can be used for analyses on the
      perfusion of coronary arteries and ventricular function. The present study
      reports the use of a new procedure for continuous measurements of left ventricle
      function during a dialytic session with the use of a recently developed portable
      gamma radiation detector (ventricular function study system). On average, left
      ventricle ejection fraction and stroke volume progressively and continuously
      decreased throughout the session (end session versus baseline: -13.8% for
      ejection fraction, -25.9% for stroke volume, P<.02). A biphasic response was
      found for heart rate: a transient modest decrease (at session midpoint, -4.2%)
      followed by an increase up to values higher than baseline (end session, +4.7%).
      Cardiac output decreased by 10.4% at session midpoint (P=.023 versus baseline)
      without further reduction in the following hours. Mean changes in systolic
      pressure paralleled data for cardiac output. Individual changes in indices of
      left ventricle function were scattered and strongly were correlated with
      thickness of interventricular septum and telediastolic left ventricular volume
      measured by standard echocardiogram in the interdialytic period (R>.75, P<.05).
      Data indicate that the ventricular function study system could be a powerful tool
      for characterization of the profile of left ventricular function in hemodialyzed
      patients.

PMID- 16412834
TI  - Prevalence of antiphospholipid antibodies in patients with neurological symptoms.
AB  - OBJECTIVE AND PURPOSE: Neurological involvement is a common feature of the
      antiphospholipid syndrome (APS). A variety of thrombotic and non-thrombotic
      manifestations may accompany the presence of antiphospholipid antibodies (aPL).
      PATIENTS AND METHODS: We retrospectively reviewed the prevalence of aPL in a
      cohort of over 350 unselected patients from a neurological clinic and studied the
      neurological manifestations of APS. RESULTS: We found that within this cohort the
      prevalence of aPL was about 15%. Most of the patients with aPL suffered from
      strokes and transient ischemic attacks (TIA). One patient died from spinal
      infarction. Non-thrombotic manifestations also occurred in 40% of these patients,
      such as multiple sclerosis, chorea, seizures or cerebral malignancies. No
      significant correlations of the titres or different types of aPL and the type of
      the neurological symptoms could be found. In comparison to age and sex matched
      patients of the cohort where the presence of aPL could be excluded, the
      occurrence of non-thrombotic manifestations was significantly more frequent and
      varied in the group of patients with aPL. The higher incidence of stroke in the
      non-APS group could be explained by the significantly higher presence of other
      laboratory risk factors, mainly hypercholesterinemia. CONCLUSION: This
      investigation indicates that aPL may play an important role in the etiology of
      various neurological syndromes.

PMID- 16412833
TI  - Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix
      metalloproteinase (TIMP-1) in patients with relapsing-remitting multiple
      sclerosis treated with interferon beta.
AB  - OBJECTIVES: Matrix metalloproteinases (MMPs), particularly MMP-9, facilitate T
      cell migration into the central nervous system. They play a key role in the
      disruption of the blood-brain barrier (BBB) and thus in the pathogenesis of
      multiple sclerosis. Interferon beta's (IFNbeta) ability to alter the balance
      between MMP-9 and MMP-9s natural inhibitor, tissue inhibitor of matrix
      metalloproteinase-1 (TIMP-1), may play a role in stabilizing the BBB. The aim of
      this study, was to evaluate serum MMP-9 and TIMP-1 and cerebrospinal fluid (CSF)
      TIMP-1 levels in patients with relapsing-remitting multiple sclerosis (RRMS)
      treated with IFNbeta-1a. PATIENTS AND METHODS: Blood and CSF samples from 14
      patients with RRMS before and 6 months after IFNbeta therapy and 14 age and sex
      matched controls were obtained. Levels of MMP-9 and TIMP-1 were measured using
      ELISA. RESULTS: Before treatment, patients with MS had higher levels of serum MMP
      9 and a higher MMP-9/TIMP-1 ratio than the controls. Although serum levels of
      TIMP-1 were lower in RRMS patients than in the controls, the differences did not
      reach statistical significance. CSF levels of TIMP-1 were significantly lower in
      RRMS patients. In the sixth month of IFNbeta therapy serum MMP-9 and the MMP
      9/TIMP-1 ratio were significantly decreased, whereas the changes in serum TIMP-1
      were not statistically significant. There was a significant increase in CSF TIMP
      1 levels in the sixth month of IFNbeta therapy. CONCLUSIONS: Our result shows
      that RRMS patients have an impaired MMP-9 and TIMP-1 balance, and that 6 months
      of IFNbeta therapy is beneficial in restoring this balance.

PMID- 16412835
TI  - Endoscopic third ventriculostomy in the treatment of shunt-related over-drainage:
      Preliminary experience with a new approach how to render ventricles navigable.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is increasingly used for the
      treatment of shunt-related complications in hydrocephalic patients, particularly
      if the etiology of the underlying hydrocephalus is of obstructive nature.
      PURPOSE: Due to the slit-like configuration of the ventricles, ventricular
      dilatation must be achieved prior to ETV in patients with problems due to over
      drainage. This has been accomplished by ligating or explanting the shunt. Here we
      present an alternative procedure using a gravitational antisiphon device.
      MATERIALS AND METHODS: In two patients with over-drainage due to shunted
      occlusive hydrocephalus ventricles were dilated by integrating an antisiphon
      device (Miethke ShuntAssistant, Aesculap AG, Tuttlingen, Germany) into their
      shunt systems. The resistance of the antisiphon device, which is available in
      configurations from 10 to 35 cm H2O was chosen 10 cm H2O higher than necessary to
      prevent siphoning in the individual patient. RESULTS: Both patients gradually
      recovered from their over-drainage symptoms and the ventricles enlarged enough to
      allow access with an endoscope. Using a standard procedure, ETV was performed 7
      days and 1 month later, respectively. In the same operative session the shunts
      were occluded. Shunts were removed within 6 weeks after ETV. During follow-up of
      more than 3 years, both patients remained free of symptoms. CONCLUSION: The
      incorporation of an antisiphon device with resistance level selected 10 cm H2O
      higher than needed to prevent anti-siphoning into a pre-existing shunt system in
      patients suffering from shunt-related over-drainage is a safe and effective
      technique to render ventricles large enough to allow endoscopic access for ETV.

PMID- 16412836
TI  - Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963
      patients.
AB  - OBJECTIVE: Vascular occlusion is not an uncommon event in malignancy. However,
      the frequency of ischemic stroke after chemotherapy has been mentioned only
      occasionally in clinical studies. A large-scale study is lacking. METHODS: A
      retrospective study was conducted at Chang Gung Memorial Hospital, Kaohsiung,
      Taiwan, to analyze the incidence of ischemic stroke post-chemotherapy, further,
      to evaluate a possible causative relationship between the ischemic stroke and the
      chemotherapy regimen, the interval between the latest chemotherapy session and
      onset of ischemic stroke and the survival of patients with ischemic stroke post
      chemotherapy. The data were retrieved from the Cancer Database from 1993 to 2004.
      RESULTS: During this period, a total of 10,963 patients, with malignancies were
      followed-up for 1 month after chemotherapy, underwent 45,294 chemotherapy
      sessions. Among this group, there were 15 patients experiencing 16 ischemic
      strokes within the first month after the latest chemotherapy. Among them, 14
      patients were followed-up until death and one patient was lost in follow-up after
      discharge against medical advice. The incidence of post-chemotherapy ischemic
      stroke was 0.137% and the frequency of chemotherapy cycles complicated by
      ischemic stroke was 0.035%. Adenocarcinoma was the most common histological type
      not only in ischemic stroke (40%) but also in overall patients (36.7%). The
      hemispheric stroke with middle cerebral artery territory involvement was the most
      common image finding. Platinum compounds, especially cisplatin, were the most
      commonly used chemotherapeutic agents for ischemic stroke patients. Twelve (75%)
      of these 16 ischemic strokes occurred within 10 days of the latest chemotherapy
      session and 10 (62.5%) occurred after the first cycle of chemotherapy. The median
      survival after ischemic stroke was 4 weeks. CONCLUSION: Our results provide
      valuable data on the relationship between malignancy, treated with chemotherapy,
      and ischemic stroke. The risk of ischemic stroke after chemotherapy is predicted
      by the use of cisplatin-based chemotherapy not cancer histologic type. Infarction
      usually involves the territorial subtype, causes obvious neurological
      disabilities and carries a grave prognosis.

PMID- 16412837
TI  - Primary spinal extranodal Hodgkin's disease at two levels.
AB  - About 90% of Hodgkin's disease cases originate from lymph nodes whereas 10% from
      extranodal regions. Patients rarely present with spinal cord compression due to
      epidural Hodgkin's disease. Primary spinal extradural Hodgkin's disease which
      does not have any other organ involvement in the body is even rarer. A 39-year
      old male patient who complained of lumbar pain had normal findings upon
      neurological examination. Radiological examination revealed a mass on the
      epidural space at level L3 and the involvement of the vertebral corpus
      accompanied by the involvement of C6 vertebral body. Primary focus could not be
      identified despite further investigation. The patient underwent L3 laminectomy
      and posterior decompression and biopsy was obtained from the lesion extending to
      epidural space. The pathological result was reported as lymphocyte dominant type
      Hodgkin's disease. Flow cytometry was performed to the lesion, also. The patient
      was evaluated as Stage 4A according to Ann Arbor classification. Postoperative
      radiotherapy was applied to lumbar and cervical region. In the literature we have
      not come across any case of primary spinal extranodal Hodgkin's disease with
      involvement at two levels. In conclusion, although it might be extremely rare,
      primary spinal extranodal Hodgkin's disease with involvement at two levels might
      be observed.

PMID- 16412838
TI  - Nightmare of lumbar disc surgery: iliac artery injury.
AB  - Intra-operative injuries of pelvic vessels are quite infrequent but serious
      complications of lumbar disc surgery. Injury may cause laceration of the vessel
      with acute life threatening retroperitoneal haemorrhage, formation of
      pseudoaneurysms or arteriovenous fistulae in the late phase. It is important for
      surgeons to be aware of these potentially fatal complications. Authors reported a
      case of major vascular injury recognised intra-operatively during posterior
      lumbar discectomy and repaired immediately.

PMID- 16412839
TI  - Intracranial gliofibroma mimicking a meningioma: a case report and review of
      literature.
AB  - Gliofibromas are rare glio-mesenchymal tumors composed of astrocytic and benign
      mesenchymal components, which commonly occur in the first two decades of life.
      They are not listed as a distinct entity in the current WHO classification of CNS
      tumors. Their biological behaviour is unknown, and histogenesis is debatable. We
      describe a case of histopathologically proven gliofibroma in the region of the
      left quadrigeminal plate in a 15-year-old child that mimicked a tentorial
      meningioma both at imaging and surgery. Post-operatively, the residual tumor
      regrew to a size similar to the initial mass (4 cm x 3.6 cm x 3.5 cm), within one
      and a half years after the first surgery. The histopathology of the tumor was
      similar on both occasions. Although a poor prognosis has been characteristically
      noted in gliofibromas with high-grade glial component, but the present case had
      recurrence despite being of low-grade, thus highlighting the uncertain behaviour
      of this rare tumor.

PMID- 16412840
TI  - Multiple brain abscesses following surgical treatment of a perianal abscess.
AB  - We report a case of multiple brain abscesses (BAs) in a 67-year-old man with
      symptoms of progredient disorientation and amnestic aphasia. Onset of symptoms
      occurred one week after surgical treatment of a perianal abscess. No other source
      of infection was identified and the abscesses were limited to the brain. The
      immune status was normal but a patent foramen ovale (pFO) was found. The patient
      was treated with high-dose antibiotics, leading to a complete radiological
      disappearance of the BAs. Hematogenous spread of infectious emboli from a
      perianal focus exclusively to the brain is very rare. In our patient, the
      mechanisms of infectious spread into the brain might have occurred via a cardiac
      right-to-left shunt or alternatively via the non-valvular vertebral venous
      system. In this manuscript, both pathways are critically reviewed.

PMID- 16412841
TI  - Friday night palsy: an unusual case of brachial plexus neuropathy.
AB  - Brachial plexopathy can result from traction injury, radiation injury, local or
      metastatic cancer, hereditary, or idiopathic causes. However, brachial plexopathy
      resulting from malposition of an arm during sleep, similar to Saturday night
      palsy, has not been reported. We report a case of brachial plexus neuropathy that
      occurred after the patient slept on his shoulder and arm following excessive
      alcohol consumption on a Friday night.

PMID- 16412842
TI  - Efficacy of a 3-day course of albendazole treatment in patients with a single
      neurocysticercosis cyst.

PMID- 16412843
TI  - Resolution of cluster headache after closure of an anterior communicating artery
      aneurysm: the role of pericarotid sympathetic fibres.
AB  - We report the case of a patient suffering from migraine without aura since
      childhood who, at the age of 58 years, developed cluster headache (CH) attacks.
      This second type of headache was related to an aneurysm of the anterior
      communicating artery (ACoA) whose bursting caused subarachnoid haemorrhage. The
      aneurysm's clipping made the cluster headache subside and there was no recurrence
      for almost four years. However, nine months after haemorrhage, the patient
      experienced new migraine without aura attacks. As a pathogenetic interpretation
      of this secondary cluster headache, we discuss the possible role of pericarotid
      sympathetic nerves in cluster headache attacks. We suggest that the surgical
      dissection of the pericarotid sympathetic fibres could prevent the onset of the
      cluster headache attacks by cutting part of the circuit underlying it.

PMID- 16412844
TI  - Third ventricle glioblastoma. Case report and review of literature.
AB  - A glioblastoma presenting as a solitary third ventricle mass is exceptional. CASE
      DESCRIPTION: We report the case of a 29-year-old woman who lost consciousness,
      was taken to hospital and referred a previous history of depression and diabetes
      insipidus. Magnetic resonance imaging study revealed a heterogeneous anterior
      third ventricle mass with ring enhancement after contrast administration. It was
      approached and subtotally resected by a transcortical-transventricular route and
      histological diagnosis proved it to be a glioblastoma. There are only two other
      similar well-described cases and another nine have been previously reported in
      surgical series of high grade gliomas and glioblastomas. The possible origin of
      this lesion is discussed.

PMID- 16412845
TI  - Lumbar diskectomy in a human-habituated mountain gorilla (Gorilla beringei
      beringei).
AB  - The authors report a case of a human-habituated mountain gorilla, Alvila,
      resident at the San Diego Zoo, who was found to have a herniated intervertebral
      lumbar disc after being attacked by the gorilla troop's silverback male gorilla.
      Ultimately, the gorilla required surgical intervention for her disease and made a
      full recovery. To our knowledge, this is the only known case of spine surgery. A
      36-year-old female human-habituated mountain gorilla (Gorilla beringei beringei),
      resident at the San Diego Zoo, was noticed by caregivers to walk with a
      substantial limp after being attacked by the gorilla troop's silverback male
      gorilla. Magnetic resonance (MR) imaging of her lumbar spine revealed a large
      herniated disk at the L1-2 level on the right. This finding appeared to correlate
      well with the gorilla's symptoms. The gorilla underwent a lumbar diskectomy under
      loupe. Post-operatively the gorilla did very well. The right leg weakness was
      immediately improved post-operatively. The gorilla continued to "crutch walk"
      initially, swinging on the upper extremities and not bearing weight on the
      lowers. However, by 2 weeks the limp was no longer noticeable to the zoo
      caregivers. The wound healed well and there was no evidence of wound infection or
      CSF leak. The gorilla was reunited with her troop and has reintegrated well
      socially. With 10 months of follow-up, the gorilla continues to do well. This is
      the only known case of spine surgery in a gorilla. For best surgical results, one
      needs to consider the similarities and differences between the gorilla and human
      vertebral anatomy. We believe that careful pre-operative planning contributed to
      the good early post-operative result. Ultimate assessment of the long-term
      outcome will require additional follow-up.

PMID- 16412846
TI  - Myxopapillary ependymoma of the fourth ventricle.
AB  - Myxopapillary ependymoma is a benign variant of ependymoma, occurring almost
      exclusively in the cauda equina region of the back. Here, we report an extremely
      rare case of primary myxopapillary ependymoma, and also present our review of the
      existing literature. This tumor occurred in the fourth ventricle of a 62-year-old
      woman. The patient had complained of dizziness and general weakness, persisting
      for the prior 6 months. The patient underwent surgical removal of the tumor.
      Imaging studies of the spine were normal. Microscopically, the cut sections of
      the tumor revealed papillary formation surrounding areas containing both
      hyalinized blood vessels and myxoid degeneration. The histological findings were
      consistent with those of tumors originating in the filum terminale. The patient's
      postoperative course was uneventful, and she was doing well on follow-up, 15
      months after surgery. This is the second reported case of fourth ventricular
      myxopapillary ependymoma.

PMID- 16412847
TI  - T-wave alternans and the susceptibility to ventricular arrhythmias.
AB  - T-wave alternans (TWA) reflects beat-to-beat fluctuations in the
      electrocardiographic T-wave, and is associated with dispersion of repolarization
      and the mechanisms for sudden cardiac arrest (SCA). This review examines the
      bench-to-bedside literature that, over decades, has linked alternans of
      repolarization in cellular, whole-heart, and human studies with spatial
      dispersion of repolarization, alternans of cellular action potential, and
      fluctuations in ionic currents that may lead to ventricular arrhythmias.
      Collectively, these studies provide a foundation for the clinical use of TWA to
      reflect susceptibility to ventricular arrhythmias in several disease states. This
      review then provides a contemporary evidence-based framework for the use of TWA
      to enhance risk stratification for SCA, identifying populations for whom TWA is
      best established, those for whom further studies are required, and areas for
      additional investigation.

PMID- 16412848
TI  - A new paradigm for physiologic ventricular pacing.
AB  - Clinical trials in patients with pacemakers for sinus node dysfunction or
      atrioventricular block (AVB) and implantable cardioverter-defibrillators provide
      increasing evidence showing that desynchronization of ventricular electrical
      activation and contraction, induced by conventional right ventricular apex (RVA)
      pacing, is a serious threat for long-term cardiac morbidity and mortality. The
      risk of heart failure is increased even in hearts with initially normal pump
      function and in case of part-time ventricular pacing. These epidemiologic data
      fit with knowledge from decades of pathophysiological research, indicating that
      right ventricular (RV) pacing creates abnormal contraction, reduced pump
      function, hypertrophy, and ultrastructural abnormalities. This paper presents a
      new paradigm that aims to tailor ventricular pacing to the individual patient to
      achieve a way of pacing that is as physiologic as possible. In patients without
      AVB and no intraventricular conduction abnormalities, ventricular pacing should
      be avoided as much as possible, using atrial-based pacing. In patients with AVB,
      alternate single-site RV or left ventricular pacing or biventricular pacing may
      be superior to RVA pacing. Efforts to optimize the pacing mode or site should be
      greater in patients with a longer expected duration of pacing, poorer cardiac
      function, and larger mechanical asynchrony. Awareness of the problem of
      desynchronization should also lead to more regular monitoring of cardiac pump
      function and mechanical asynchrony in any patient with ventricular pacing.

PMID- 16412849
TI  - Door-to-balloon time with primary percutaneous coronary intervention for acute
      myocardial infarction impacts late cardiac mortality in high-risk patients and
      patients presenting early after the onset of symptoms.
AB  - OBJECTIVES: The purpose of this study was to evaluate the impact of door-to
      balloon time with primary percutaneous coronary intervention (PCI) on late
      cardiac mortality. BACKGROUND: The impact of door-to-balloon time on outcomes is
      controversial, and the impact on late mortality has not been studied. METHODS:
      Consecutive patients (n = 2,322) treated with primary PCI from 1984 to 2003 were
      prospectively identified and followed up for a median of 83 months. RESULTS:
      Prolonged door-to-balloon times (0 to 1.4 h vs. 1.5 to 1.9 h vs. 2.0 to 2.9 h vs.
      > or =3.0 h) were associated with higher in-hospital mortality (4.9% vs. 6.1% vs.
      8.0% vs. 12.2%, p < 0.0001) and late mortality (12.6% vs. 16.4% vs. 20.4% vs.
      27.1% at 7 years, p < 0.0001) and were an independent predictor of late mortality
      by Cox regression (p = 0.0004). Prolonged door-to-balloon times (> or =2 h vs. <2
      h) were associated with higher late mortality in high-risk patients (32.5% vs.
      21.5%; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.22 to 1.90; p =
      0.0002) but not in low-risk patients (10.8% vs. 9.2%; HR, 1.13; 95% CI, 0.78 to
      1.64; p = 0.53) and in patients presenting early (< or =3 h) (24.7% vs. 15.0%;
      HR, 1.54; 95% CI, 1.24 to 1.90; p = 0.0001) but not late (>3 h) (21.1% vs. 18.5%;
      HR, 0.95; 95% CI, 0.62 to 1.45; p = 0.80). CONCLUSIONS: Delays in door-to-balloon
      time impact late survival in high-risk but not low-risk patients and in patients
      presenting early but not late after the onset of symptoms. These findings have
      implications for the triage of patients for primary PCI.

PMID- 16412850
TI  - Remote-control percutaneous coronary interventions: concept, validation, and
      first-in-humans pilot clinical trial.
AB  - OBJECTIVES: This study was designed to assess the feasibility and safety of a
      Remote Navigation System (RNS, NaviCath, Haifa, Israel) in which the angioplasty
      guidewire, the balloon, and the stent are navigated via a computerized system.
      BACKGROUND: Percutaneous coronary interventions (PCIs) are manually performed
      under fluoroscopic guidance, requiring lead protection for the operators. A
      system in which the operator can remotely, safely, and precisely navigate the
      procedure during PCI would have clear advantages. METHODS: The RNS involves a
      computer-controlled wire and delivery system navigator. Following preclinical
      validation, the system was assessed in patients undergoing single-vessel PCI.
      RESULTS: The study involved 18 patients (age 55.9 years, 16% women). The RNS
      successfully crossed lesions with the guidewire in 17 patients. The stent was
      then advanced by the advance/rotate mode and adequately positioned in 15 of 17
      cases. Technical malfunction was encountered in three patients in whom the
      procedure was successfully completed manually. Direct stenting was employed in 10
      of 18 patients, pre-dilation in 7 patients, and after-stent balloon dilation in 5
      patients. The total fluoroscopy time for 17 RNS patients was compared with the
      corresponding time of 20 consecutive patients who underwent standard single
      lesion PCI. Fluoroscopy time was similar for both procedures, with 8.8 +/- 4.8
      min with the RNS versus 9.1 +/- 3.5 min with the standard techniques (p = NS).
      Clinical success was 100% and technical success 94% for the guidewire and 83% for
      the overall procedure. CONCLUSIONS: The use of the RNS for guidewire, balloon,
      and stent manipulation during PCI appears safe and feasible for the treatment of
      patients with coronary stenosis. The system offers operator radiation safety and
      may enhance precision of stent placement and balloon dilation strategies.

PMID- 16412851
TI  - Elevated plaque temperature in non-culprit de novo atheromatous lesions of
      patients with acute coronary syndromes.
AB  - OBJECTIVES: We investigated whether there is increased temperature in non-culprit
      lesions, and the correlation of clinical syndrome with heat production of non
      culprit lesions. BACKGROUND: There is a controversy regarding whether there is
      widespread inflammation involving non-culprit lesions, or whether inflammatory
      involvement is limited to the culprit lesion. Coronary thermography assesses the
      local inflammatory involvement in atherosclerotic lesions. METHODS: We included
      patients suffering from stable angina (SA) or acute coronary syndrome (ACS). All
      patients had two or more angiographically detectable lesions at different
      arteries. Culprit lesions should be identified in all patients. Patients with
      chronic total occlusions and multiple significant lesions at the culprit vessel
      were excluded. We measured at each non-culprit lesion the temperature difference
      (DeltaT) between the atherosclerotic plaque and the proximal vessel wall
      temperature. RESULTS: The study population included 42 patients: 23 with SA, 19
      with ACS. The DeltaT in non-culprit lesions was 0.08 +/- 0.07 degrees C. Patients
      with ACS had a higher temperature difference in non-culprit lesions compared with
      patients with SA (ACS 0.11 +/- 0.08 degrees C vs. SA 0.05 +/- 0.06 degrees C; p <
      0.01). The mean value of DeltaT in non-culprit lesions was higher in the
      untreated group compared with the treated group with statins (0.11 +/- 0.10
      degrees C vs. 0.06 +/- 0.05 degrees C; p = 0.05). CONCLUSIONS: The results of
      this study show that heat is generated in non-culprit lesions. Moreover, in
      patients with ACS, temperature difference is increased compared with patients
      with stable angina.

PMID- 16412852
TI  - Elevated placental growth factor levels are associated with adverse outcomes at
      four-year follow-up in patients with acute coronary syndromes.
AB  - OBJECTIVES: This study sought to evaluate the predictive value of baseline
      placental growth factor (PlGF) for long-term cardiovascular events in acute
      coronary syndromes (ACS). BACKGROUND: A biomarker of vascular inflammation, PlGF
      is identified as a powerful predictor for short-term outcome in patients with
      ACS. METHODS: In 544 patients who were enrolled in the placebo arm of the c7E3
      Fab Anti Platelet Therapy in Unstable REfractory angina (CAPTURE) trial, PlGF
      levels were determined as well as markers of myocardial necrosis (troponin T
      [TnT]), general inflammation (high-sensitivity C-reactive protein [hsCRP]), and
      platelet activation (soluble CD40 ligand [sCD40L]). Cox proportional hazard
      regression analyses were applied to evaluate the relationship between biomarkers
      and the occurrence of all-cause death or non-fatal myocardial infarction during a
      median follow-up period of four years. RESULTS: Patients with PlGF levels in the
      fourth and fifth quintile (>27 ng/l) had higher mortality than those with lower
      levels (10.8% vs. 3.2%; hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6
      to 7.1), as well as a higher incidence of the composite end point of death or
      myocardial infarction (27.6% vs. 11.3% events; HR, 2.6; 95% CI, 1.7 to 3.9). The
      relationship between PlGF and the composite end point remained significant after
      adjustment for TnT, sCD40L, and hsCRP (adjusted HR, 3.3; 95% CI, 2.0 to 5.4).
      CONCLUSIONS: In patients with ACS, elevated plasma levels of PlGF are associated
      with adverse cardiac outcomes during long-term follow-up. These data suggest that
      PlGF as a more specific marker of vascular inflammation should be considered for
      risk stratification of patients with ACS rather than general markers of
      inflammation.

PMID- 16412854
TI  - Transcatheter closure of perimembranous ventricular septal defects using the new
      Amplatzer membranous VSD occluder: results of the U.S. phase I trial.
AB  - OBJECTIVES: This phase I study attempted to report the initial safety and
      efficacy results of transcatheter closure of perimembranous ventricular septal
      defects (PmVSDs) using the new Amplatzer Membranous VSD Occluder (AGA Medical
      Corp., Golden Valley, Minnesota) in the U.S. BACKGROUND: The most common
      congenital heart disease is PmVSD. Surgical repair is widely accepted, but still
      carries a small but definite risk of morbidity and mortality. METHODS: Between
      October 2003 and August 2004, a total of 35 patients with PmVSD underwent an
      attempt of transcatheter closure under transesophageal and/or intracardiac
      echocardiographic guidance. The median age was 7.7 years (range, 1.2 to 54.4
      years) and median weight was 25 kg (range, 8.3 to 110 kg). The median Qp/Qs ratio
      was 1.8 (range, 1 to 4), and the median VSD size as assessed by echocardiography
      was 7 mm (range, 4 to 15 mm). RESULTS: The attempt to place a device was
      successful in 32 patients (91%). The median device size used was 10 mm (range, 6
      to 16 mm). The complete closure rates by echocardiography at 10 min
      (transesophageal/intracardiac), 24 h, 1 month, and 6 months (transthoracic) were
      47% (15/32), 63% (20/32), 78% (25/32), and 96% (27/28), respectively. The median
      fluoroscopy time was 36 min (range, 14 to 191 min), and the median total
      procedure time was 121 min (range, 67 to 276 min). Three patients (8.6%) had
      serious adverse events of complete heart block, peri-hepatic bleeding, and
      rupture of tricuspid valve chordae tendineae. No other patient encountered
      serious adverse events during the follow-up. CONCLUSIONS: Transcatheter closure
      of a PmVSD is technically feasible and seems safe enough in children over 8 kg in
      weight to warrant continuation of clinical trials to assess the long-term safety
      and efficacy.

PMID- 16412853
TI  - Frequency and clinical implications of discordant creatine kinase-MB and troponin
      measurements in acute coronary syndromes.
AB  - OBJECTIVES: We sought to evaluate the association between discordant cardiac
      marker results and in-hospital mortality and treatment patterns in patients with
      non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND:
      Creatine kinase-MB (CK-MB) and cardiac troponins (cTn) are often measured
      concurrently in patients with NSTE ACS. The significance of discordant CK-MB and
      cTn results is unknown. METHODS: Among 29,357 ACS patients in the CRUSADE
      initiative who had both CK-MB and cTn measured during the first 36 hours, we
      examined relationships of four marker combinations (CK-MB-/cTn-, CK-MB+/cTn-, CK
      MB-/cTn+, and CK-MB+/cTn+) with mortality and American College of
      Cardiology/American Heart Association guidelines-recommended acute care. RESULTS:
      The CK-MB and cTn results were discordant in 28% of patients (CK-MB+/cTn-, 10%;
      CK-MB-/cTn+, 18%). In-hospital mortality was 2.7% among CK-MB-/cTn- patients;
      3.0%, CK-MB+/cTn-; 4.5%, CK-MB-/cTn+; and 5.9%, CK-MB+/cTn+. After adjustment for
      other presenting risk factors, patients with CK-MB+/cTn- had a mortality odds
      ratio (OR) of 1.02 (95% confidence interval [CI] 0.75 to 1.38), those with CK-MB
      /cTn+ had an OR of 1.15 (95% CI 0.86 to 1.54), and those with CK-MB+/cTn+ had an
      OR of 1.53 (95% CI 1.18 to 1.98). Despite variable risk, patients with CK-MB+/cTn
      and CK-MB-/cTn+ were treated similarly with early antithrombotic agents and
      catheter-based interventions. CONCLUSIONS: Among patients with NSTE ACS, an
      elevated troponin level identifies patients at increased acute risk regardless of
      CK-MB status, but an isolated CK-MB+ status has limited prognostic value.
      Recognition of these risk differences may contribute to more appropriate early
      use of antithrombotic therapy and invasive management for all cTn+ patients.

PMID- 16412855
TI  - Surgical versus percutaneous occlusion of ostium secundum atrial septal defects:
      results and cost-effective considerations in a low-income country.
AB  - OBJECTIVES: We compared the effectiveness and cost of percutaneous occlusion
      using an Amplatzer septal occluder (ASO) (AGA Medical Corp., Golden Valley,
      Minnesota) device compared with surgical closure of an ostium secundum atrial
      septal defect (ASD II) in Guatemala. BACKGROUND: The percutaneous occlusion of
      ASD II in first-world nations seems to offer better clinical results and lower
      cost compared with surgical closure. METHODS: We reviewed the clinical course of
      111 patients referred to our institution for closure of isolated ASD II.
      Successful closure was assessed immediately after the procedures and at 12
      months. Actual hospital costs were calculated for every patient who underwent
      either of the two procedures. RESULTS: Eighty-three patients with ASD II (75%)
      were selected for percutaneous occlusion with the ASO device, and the remaining
      28 patients (25%) underwent surgical closure. In the device group, in 72 patients
      (86.7%) devices were successfully deployed. At immediate and 12-month follow-up,
      the complete closure rate was 87.5% (63 of 72 patients) and 97.2% (70 of 71
      patients), respectively. In the surgical group, all patients had successful
      closure immediately after the procedure and at 12 months. Surgical closure
      offered a 27% cost savings in comparison with percutaneous occlusion (U.S.
      3,329.50 dollars +/- 411.30 dollars and U.S. 4,521.03 dollars +/- 429.71 dollars;
      p < 0.001, respectively). Cost of the device (U.S. 2,930.00 dollars) proved to be
      the main cause for this difference. CONCLUSIONS: We confirmed the clinical
      advantages of percutaneous occlusion over surgical closure of ASD II. However,
      percutaneous occlusion costs were higher compared with surgical closure. In
      Guatemala, where health care resources are limited, ASD II closure with the ASO
      device did not prove to be cost-effective.

PMID- 16412856
TI  - Atorvastatin improves left ventricular systolic function and serum markers of
      inflammation in nonischemic heart failure.
AB  - OBJECTIVES: This study examined the effect of statin therapy on vascular markers
      of inflammation and echocardiographic findings in patients with nonischemic forms
      of cardiomyopathy. BACKGROUND: Despite advances in therapy, morbidity and
      mortality from heart failure (HF) remain high. We wished to determine whether
      treatment with atorvastatin affects left ventricular (LV) systolic function and
      markers of inflammation in patients with nonischemic HF. METHODS: A total of 108
      patients with nonischemic HF and a left ventricular ejection fraction (LVEF) < or
      =35% were randomized to either atorvastatin 20 mg/day or placebo in a double
      blinded fashion for a 12-month period. The LVEF and LV end-diastolic diameter
      (LVEDD) and left ventricular end-systolic diameter (LVESD) were determined by
      echocardiography. Serum markers of inflammation and oxidation were also measured.
      RESULTS: The LVEF increased from 0.33 +/- 0.05 to 0.37 +/- 0.04 (p = 0.01) in the
      atorvastatin group over the 12-month follow-up period, whereas those patients in
      the placebo group experienced a decline in ejection fraction during the same time
      period. In addition, LVEDD was reduced from 57.1 +/- 5.9 mm to 53.4 +/- 5.1 mm (p
      = 0.007) and LVESD was reduced from 42.4 +/- 3.8 mm to 39.1 +/- 3.8 mm (p = 0.02)
      in the cohort of patients treated with atorvastatin; these dimensions increased
      in the placebo group. There was an increase in erythrocyte superoxide dismutase
      (E-SOD) activity, and there were significant reductions in serum levels of high
      sensitivity C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor
      alpha receptor II (TNF-alpha RII) in the atorvastatin group. CONCLUSIONS: The use
      of atorvastatin in patients with nonischemic HF improves LVEF and attenuates
      adverse LV remodeling. The effects on soluble levels of several inflammatory
      markers with atorvastatin suggest, in part, mechanisms by which statins might
      exert their beneficial effects in nonischemic HF.

PMID- 16412857
TI  - Neutral effect on markers of heart failure, inflammation, endothelial activation
      and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non
      diabetic patients with non-ischemic cardiomyopathy and average low-density
      lipoprotein level.
AB  - OBJECTIVES: This study sought to determine the effect of aggressive 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on
      surrogate markers in non-ischemic cardiomyopathy (NICM) patients and average low
      density lipoprotein (LDL) concentrations. BACKGROUND: The effects of statins may
      well go beyond lipid lowering, and these pleiotropic effects may be of benefit in
      the treatment of heart failure. METHODS: Fifteen patients with NICM on standard
      maximized heart failure medication were enrolled in a randomized, double-blinded,
      placebo-controlled, crossover trial. Patients received 80 mg atorvastatin (ATV)
      or matching placebo for a 12-week treatment period with a minimum of an 8-week
      washout period. The following surrogate markers were evaluated: N-terminal-pro
      brain natriuretic peptide, high-sensitivity C-reactive protein, oxidized LDL
      antibody, soluble receptor tumor necrosis factor, tumor necrosis factor-alpha,
      circulating levels of vascular adhesion molecule-1, intercellular adhesion
      molecule-1, P-selectin, non-invasive endothelial function studies, and heart rate
      variability. RESULTS: After ATV therapy, there was a significant decrease in LDL
      concentration from 110 +/- 27 mg/dl to 55 +/- 18 mg/dl (p < 0.05). There were no
      differences between ATV and placebo with regard to the surrogate markers
      measured. CONCLUSIONS: Based on these findings, it seems that the administration
      of high-dose statins to a heart failure population with modest LDL levels and no
      other indication for statin therapy was neither beneficial nor detrimental as
      determined by surrogate marker measures. Further studies are needed to determine
      whether there is an appropriate patient population and optimal dose (LDL
      concentration) for the treatment of systolic heart failure with statin therapy.

PMID- 16412858
TI  - The emerging role of statins in the treatment of heart failure.

PMID- 16412859
TI  - Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in
      the general community: determinants and detection of left ventricular
      dysfunction.
AB  - OBJECTIVES: This study sought to characterize factors influencing amino-terminal
      pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT
      proBNP to detect left ventricular (LV) dysfunction in a large community sample.
      BACKGROUND: Secretion of BNP increases in cardiac disease, making BNP an
      attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is
      a new biomarker. We evaluated factors influencing NT-proBNP in normal patients
      and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large
      community sample. METHODS: Amino-terminal pro-BNP was determined in plasma
      samples of a previously reported and clinically and echocardiographically
      characterized random sample (n = 1,869, age > or =45 years) of Olmsted County,
      Minnesota. RESULTS: In normal patients (n = 746), female gender and older age
      were the strongest independent predictors of higher NT-proBNP. Test
      characteristics for detecting an LV ejection fraction < or =40% or < or =50% were
      determined in the total sample with receiver operating characteristic curves.
      Amino-terminal pro-BNP had significantly higher areas under the curve for
      detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total
      population and in several male and age subgroups, whereas areas were equivalent
      in female subgroups. Age- and gender-adjusted cutpoints improved test
      characteristics of NT-proBNP. Both assays detected patients with systolic and/or
      moderate to severe diastolic dysfunction to a similar degree, which was less
      robust than the detection of LV systolic dysfunction alone. CONCLUSIONS: Amino
      terminal pro-BNP in normal patients is affected primarily by gender and age,
      which should be considered when interpreting values. Importantly, in the entire
      population sample NT-proBNP performed at least equivalently to BNP in detecting
      LV dysfunction and was superior in some subgroups in detecting LV systolic
      dysfunction.

PMID- 16412860
TI  - The prevalence of thiamin deficiency in hospitalized patients with congestive
      heart failure.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence of thiamin
      deficiency (TD) in a cross section of hospitalized congestive heart failure (CHF)
      patients and to investigate factors that contribute to its development.
      BACKGROUND: Thiamin deficiency manifests as symptoms of CHF and, therefore, may
      worsen existing heart failure. Congestive heart failure patients may be at
      increased risk for TD as a result of diuretic-induced urine thiamin excretion,
      disease severity, malnutrition, and advanced age. METHODS: Erythrocyte thiamin
      pyrophosphate concentrations, using high-performance liquid chromatography, were
      measured in 100 CHF patients and compared to 50 control subjects. Variables
      including diuretics (type and dose), left ventricle dysfunction, New York Heart
      Association functional classification, creatinine clearance, thiamin intake (diet
      and supplements), malnutrition, appetite ratings, and age were related to TD
      using univariate statistics and multiple logistic regression analysis. RESULTS:
      Thiamin deficiency was more prevalent in CHF patients (33%) compared to control
      subjects (12%) (p = 0.007). Thiamin deficiency was related to urine thiamin loss
      (p = 0.03), non-use of thiamin-containing supplements (p = 0.06), and preserved
      renal function (p = 0.05). Increased urinary thiamin loss (mug/g creatinine) was
      found to be the only significant positive predictor of thiamin status on multiple
      logistic regression analysis (p = 0.03). CONCLUSIONS: One-third of hospitalized
      CHF patients were TD. In contrast to previous studies, increased urinary losses
      of thiamin were predictive of improved thiamin status. Thiamin supplementation
      may be protective against TD in the clinical setting. Future studies are
      warranted to determine if thiamin supplementation improves thiamin status and
      disease severity in CHF patients.

PMID- 16412861
TI  - Prolonged QTc interval and risk of sudden cardiac death in a population of older
      adults.
AB  - OBJECTIVES: This study sought to investigate whether prolongation of the heart
      rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the
      general population. BACKGROUND: In developed countries, sudden cardiac death is a
      major cause of cardiovascular mortality. Prolongation of the QTc interval has
      been associated with ventricular arrhythmias, but in most population-based
      studies no consistent association was found between QTc prolongation and total or
      cardiovascular mortality. Only very few of these studies specifically addressed
      sudden cardiac death. METHODS: This study was conducted as part of the Rotterdam
      Study, a prospective population-based cohort study that comprises 3,105 men and
      4,878 women aged 55 years and older. The QTc interval on the electrocardiogram
      was determined during the baseline visit (1990 to 1993) and the first follow-up
      examination (1993 to 1995). The association between a prolonged QTc interval and
      sudden cardiac death was estimated using Cox proportional hazards analysis.
      RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3
      years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc
      interval (>450 ms in men, >470 ms in women) was associated with a three-fold
      increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence
      interval, 1.3 to 4.7), after adjustment for age, gender, body mass index,
      hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus,
      myocardial infarction, heart failure, and heart rate. In patients with an age
      below the median of 68 years, the corresponding relative risk was 8.0 (95%
      confidence interval 2.1 to 31.3). CONCLUSIONS: Abnormal QTc prolongation on the
      electrocardiogram should be viewed as an independent risk factor for sudden
      cardiac death.

PMID- 16412862
TI  - QTc prolongation and sudden cardiac death: the association is in the detail.

PMID- 16412863
TI  - Characterization of radiofrequency ablation lesions with gadolinium-enhanced
      cardiovascular magnetic resonance imaging.
AB  - OBJECTIVES: This study was designed to evaluate the characteristics of gadolinium
      enhanced imaging of radiofrequency ablations. BACKGROUND: Gadolinium-enhanced
      magnetic resonance imaging (MRI) has been used successfully to evaluate tissue
      necrosis after myocardial infarction. In electrophysiology, radiofrequency energy
      is used to create a targeted myocardial necrosis for the treatment of various
      arrhythmias. METHODS: Using a power-controlled, cooled-tip 7-F catheter system,
      radiofrequency lesions (10 to 40 W for 30 s) were created on the epicardium of
      the right ventricle in eight mongrel dogs. After injection of 0.225 mmol/kg
      gadolinium, T1-weighted fast gradient echo images were obtained during a follow
      up of 10 h using an intrathoracic high-resolution coil. Radiofrequency ablations
      were analyzed on the MR images and compared with gross anatomy and
      histopathology. RESULTS: Four distinct phases of signal enhancement were
      observed. After gadolinium injection, radiofrequency lesions were delineated
      clearly as contrast-free areas of low signal intensity (contrast-to-noise ratio
      [CNR] = -21.1 +/- 19.8). Signal enhancement in the lesion periphery started 4.0
      +/- 1.8 min after injection and progressively extended toward the lesion center
      at a rate of 0.02 mm/min. Full delayed enhancement was observed after 98 +/- 21
      min (CNR = +17.8 +/- 9.0). During the follow-up period, CNR started to decrease,
      but the lesions were detectable for as long as 10 h of follow-up. During the
      first three phases of enhancement, MRI correlated well with the pathological
      findings (r = 0.88, r = 0.88, and r = 0.86 [p < 0.001], respectively).
      CONCLUSIONS: Radiofrequency ablation can be evaluated accurately by using
      gadolinium-enhanced MRI, which may allow the noninvasive assessment of procedural
      success. The dissimilar wash-in and wash-out kinetics compared with myocardial
      infarction suggest a different pathophysiological process with complete loss of
      microvasculature.

PMID- 16412864
TI  - Physiologic pacing in patients with obstructive sleep apnea: a prospective,
      randomized crossover trial.
AB  - OBJECTIVES: This study was designed to assess the impact of prevention of
      bradycardia with physiologic pacing on the severity of obstructive sleep apnea.
      BACKGROUND: Apneic episodes during sleep are associated with slowing of the heart
      rate during apnea and tachycardia with subsequent arousal. Patients with
      permanent pacemakers may have reduced episodes of sleep apnea when their
      pacemaker rate is set faster than their spontaneous nocturnal heart rate.
      METHODS: We conducted a prospective, randomized, single-blind crossover trial of
      temporary atrial pacing in obstructive sleep apnea to reduce the apnea hypopnea
      index (AHI). Fifteen patients (age 60 +/- 13 years, 12 men) with moderate to
      severe obstructive sleep apnea (AHI 34 +/- 14) underwent insertion of an
      externalized atrial permanent pacing system via the left subclavian vein.
      Patients underwent overnight respiratory sleep studies in hospital, during atrial
      pacing at 75 beats/min, and with pacing turned off. The order of pacing mode was
      randomized, with crossover the subsequent night to the other mode. Patients were
      blinded to pacing mode, and the analysis of sleep recordings was blind to pacing
      mode. RESULTS: Pacing was tolerated without complications in all patients.
      Overnight physiologic pacing did not affect the AHI (pacing 39 +/- 21/h vs.
      control 42 +/- 21/h, p = 0.23, 95% confidence interval -9.3 to 2.5 for
      difference), desaturation time (pacing 3.8 +/- 6.0% vs. control 3.5 +/- 4.3%, p =
      0.70), or the minimum SaO(2) (pacing 75 +/- 10% vs. control 77 +/- 11%, p =
      0.38). There was a borderline significant reduction in circulatory time with
      pacing (pacing 23.4 +/- 3.2 s vs. control 25.5 +/- 4.4 s, p = 0.09). CONCLUSIONS:
      Temporary atrial pacing does not appear to improve respiratory manifestations of
      obstructive sleep apnea. Permanent atrial pacing in this patient population does
      not appear to be justified.

PMID- 16412865
TI  - Paradoxical increase in ventricular torsion and systolic torsion rate in type I
      diabetic patients under tight glycemic control.
AB  - OBJECTIVES: This study sought to characterize the early features of diabetic
      cardiomyopathy by magnetic resonance imaging (MRI) tagging. BACKGROUND: The
      earliest manifestations of diabetic cardiomyopathy have not been well
      established, especially under tight glycemic management. We hypothesized that
      torsion measurements would identify subclinical contractile alterations in type I
      diabetics with normal left ventricular ejection fraction, mass, blood pressure,
      and aggressive glycemic control. We also sought to characterize the influence of
      elevated resting heart rates (HRs) of diabetics on torsion. METHODS: Sixteen
      patients with type I diabetes and 10 control patients underwent cine and tagged
      MRI with a 1.5-T scanner. Torsion, strain, and their rates were measured. To
      quantify the influence of chronotropic and inotropic stimulation on torsion, nine
      healthy volunteers underwent MRI tagging at rest, after atropine injection, and
      after exercise. RESULTS: Diabetic patients (hemoglobin A1c, 6.8 +/- 0.4%) had a
      higher resting HR (77.0 +/- 12.4 beats/min vs. 59.0 +/- 5.6 beats/min; p < 0.01),
      higher maximal torsion by 23% (3.5 +/- 0.9 degrees/cm vs. 2.7 +/- 0.4 degrees/cm;
      p < 0.01) and higher maximal systolic torsion rate (TR-s) by 25% (0.013 +/- 0.003
      degrees/cm/s vs. 0.010 +/- 0.002 degrees/cm/s, p = 0.01). Torsion did not
      significantly change with chronotropic stimulation (p = 0.30). CONCLUSIONS: In
      diabetics under tight glycemic control, we observed a surprising increase in
      torsion and TR-s unrelated to chronotropic influences of HR. We propose that
      increased torsion and TR-s could represent early predictive markers of the
      propensity to cardiac dysfunction in asymptomatic type I diabetics. Furthermore,
      these findings seem fundamental to the diabetic state itself and unaccounted for
      by other comorbidities.

PMID- 16412867
TI  - Long-term caloric restriction ameliorates the decline in diastolic function in
      humans.
AB  - OBJECTIVES: We determined whether caloric restriction (CR) has cardiac-specific
      effects that attenuate the established aging-associated impairments in diastolic
      function (DF). BACKGROUND: Caloric restriction retards the aging process in small
      mammals; however, no information is available on the effects of long-term CR on
      human aging. In healthy individuals, Doppler echocardiography has established the
      pattern of aging-associated DF impairment, whereas little change is observed in
      systolic function (SF). METHODS: Diastolic function was assessed in 25 subjects
      (age 53 +/- 12 years) practicing CR for 6.5 +/- 4.6 years and 25 age- and gender
      matched control subjects consuming Western diets. Diastolic function was
      quantified by transmitral flow, Doppler tissue imaging, and model-based image
      processing (MBIP) of E waves. C-reactive protein (CRP), tumor necrosis factor
      alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) were also
      measured. RESULTS: No difference in SF was observed between groups; however,
      standard transmitral Doppler flow DF indexes of the CR group were similar to
      those of younger individuals, and MBIP-based, flow-derived DF indexes, reflecting
      chamber viscoelasticity and stiffness, were significantly lower than in control
      subjects. Blood pressure, serum CRP, TNF-alpha, and TGF-beta(1) levels were
      significantly lower in the CR group (102 +/- 10/61 +/- 7 mm Hg, 0.3 +/- 0.3 mg/l,
      0.8 +/- 0.5 pg/ml, 29.4 +/- 6.9 ng/ml, respectively) compared with the Western
      diet group (131 +/- 11/83 +/- 6 mm Hg, 1.9 +/- 2.8 mg/l, 1.5 +/- 1.0 pg/ml, 35.4
      +/- 7.1 ng/ml, respectively). CONCLUSIONS: Caloric restriction has cardiac
      specific effects that ameliorate aging-associated changes in DF. These beneficial
      effects on cardiac function might be mediated by the effect of CR on blood
      pressure, systemic inflammation, and myocardial fibrosis.

PMID- 16412866
TI  - Thromboxane-dependent CD40 ligand release in type 2 diabetes mellitus.
AB  - OBJECTIVES: The goals of this study were to characterize the platelet
      contribution to soluble CD40 ligand (sCD40L), to correlate its formation with the
      extent of oxidative stress and platelet activation, and to investigate the
      effects of improved metabolic control and low-dose aspirin on these processes.
      BACKGROUND: Inflammation, oxidative stress, and platelet activation are involved
      in the pathogenesis of type 2 diabetes (T2DM) and its complications. The CD40
      CD40L interactions result in inflammatory and pro-thrombotic responses. METHODS:
      Urinary 8-iso-prostaglandin (PG)F2alpha and 11-dehydro-thromboxane (TX)B2, in
      vivo markers of oxidative stress and platelet activation, respectively, plasma
      CD40L, and C-reactive protein (CRP) were measured in 114 T2DM patients and 114
      control patients. A randomized, parallel group, 17-day study of aspirin (30, 100,
      or 325 mg/day) was performed in 18 T2DM patients. A similar study was performed
      in six healthy volunteers (aspirin, 100 mg/day). Twenty poorly controlled T2DM
      patients were studied before and after improved metabolic control. RESULTS:
      Compared with control patients, diabetic patients showed significantly higher
      levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, sCD40L, and CRP. On multiple
      regression analysis, 11-dehydro-TXB2 and 8-iso-PGF2alpha excretion rates
      predicted sCD40L levels. Soluble CD40L linearly correlated with 11-dehydro-TXB2
      (rho = 0.67, p < 0.0001), and both were reduced after one week of aspirin (p <
      0.0026), with slow recovery over 10 days after aspirin withdrawal. Improved
      metabolic control was associated with a reduction in sCD40L, 8-iso-PGF2alpha, and
      11-dehydro-TXB2. CONCLUSIONS: This study provides several lines of evidence for
      the dependence of sCD40L release on TXA(2)-dependent platelet activation in T2DM
      and provides novel mechanistic insight into the amplification loops of persistent
      platelet activation in this setting.

PMID- 16412868
TI  - Cardiovascular aging: what we can learn from caloric restriction.

PMID- 16412869
TI  - Caffeine decreases exercise-induced myocardial flow reserve.
AB  - OBJECTIVES: We studied the acute effect of caffeine on myocardial blood flow
      (MBF) at rest and exercise in healthy volunteers at normoxia and during acute
      exposure to simulated altitude. BACKGROUND: Caffeine is a widely consumed
      stimulant, although its cardiovascular safety remains controversial and its
      effect on MBF is unknown. METHODS: 15O-labeled H2O and positron emission
      tomography (PET) were used to measure regional MBF at rest and immediately after
      supine bicycle exercise in healthy volunteers at normoxia (n = 10; mean workload,
      175 W; 98% predicted; mean age, 27 +/- 6 years) as well as during hypoxia,
      simulating an altitude of 4,500 m by inhalation of a mixture of 12.5% oxygen (n =
      8; 148 W; 78% predicted; mean age, 29 +/- 4 years). Measurements were repeated 50
      min after oral ingestion of caffeine (200 mg). Myocardial flow reserve (MFR) was
      calculated as the ratio of hyperemic to resting MBF. RESULTS: Resting MBF was not
      affected by caffeine at normoxia (1.05 +/- 0.36 ml/min/g vs. 1.17 +/- 0.27
      ml/min/g; p = NS), although it was significantly increased at hypoxia (1.71 +/-
      0.41 ml/min/g vs. 2.22 +/- 0.49 ml/min/g; p < 0.001). By contrast, exercise
      induced hyperemic MBF decreased significantly at normoxia (2.51 +/- 0.58 ml/min/g
      vs. 2.15 +/- 0.47 ml/min/g; p < 0.05) and hypoxia (5.15 +/- 0.79 ml/min/g vs.
      3.98 +/- 0.83 ml/min/g; p < 0.005 vs. baseline; p < 0.005 vs. normoxia). The MFR
      decreased by 22% at normoxia (2.53 +/- 0.69 to 1.90 +/- 0.49; p < 0.01) and by
      39% at hypoxia (3.13 +/- 0.60 to 1.87 +/- 0.45, p < 0.005; p < 0.05 vs.
      normoxia). CONCLUSIONS: In healthy volunteers, a caffeine dose corresponding to
      two cups of coffee (200 mg) significantly decreased exercise-induced MFR at
      normoxia and was even more pronounced during exposure to altitude.

PMID- 16412870
TI  - Treadmill exercise produces larger perfusion defects than dipyridamole stress N
      13 ammonia positron emission tomography.
AB  - OBJECTIVES: The aim of this study was to compare treadmill exercise (TEX) and
      dipyridamole stress on the uptake and retention of N-13 ammonia. BACKGROUND: Size
      and severity of stress-induced myocardial perfusion defects are clinically
      important. Because ammonia uptake and retention seems to be related to perfusion,
      viability, and metabolism, exercise stress might induce larger perfusion defects
      than dipyridamole stress. METHODS: Twenty-six patients underwent TEX and
      dipyridamole stress N-13 ammonia positron emission tomography (PET). Images were
      assessed with a 17-segment model and a five-point score. Summed stress score
      (SSS), summed rest score (SRS), and summed difference score (SDS) were
      calculated. Left ventricular (LV) defect sizes were measured quantitatively with
      a 70% threshold for abnormal perfusion. RESULTS: Compared with dipyridamole
      stress, TEX yielded larger SSS (9.1 +/- 5.7 vs. 6.9 +/- 5.9; p < 0.01), SDS (5.8
      +/- 4.7 vs. 3.7 +/- 4.6; p < 0.02), and percentage of LV stress defect (19.3 +/-
      11.5% vs. 13.8 +/- 13.6%; p < 0.02). CONCLUSIONS: In patients achieving adequate
      exercise, TEX N-13 ammonia PET myocardial perfusion imaging (MPI) yields larger
      stress perfusion defects than dipyridamole stress and might reflect the true
      myocardial ischemic burden. Treadmill exercise might be the preferred method of
      stress for routine N-13 ammonia PET MPI.

PMID- 16412871
TI  - Impact of hospital volume on racial disparities in cardiovascular procedure
      mortality.
AB  - OBJECTIVES: We assessed use of low-volume hospitals by race and ethnicity for
      major cardiovascular procedures and determined whether hospital volume is an
      important factor explaining racial and ethnic differences in post-procedure
      mortality. BACKGROUND: Low hospital volume predicts mortality for cardiovascular
      procedures and could be a mediator of racial and ethnic differences in procedure
      outcomes. METHODS: We analyzed data from 719,679 hospitalizations for cardiac
      artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty
      (PTCA), abdominal aortic aneurysm (AAA) repair, and carotid endarterectomy (CEA)
      from 1998 to 2001 using the Nationwide Inpatient Sample. We used multivariate
      logistic regression to assess whether race predicts use of low-volume hospitals
      and the relative contribution of hospital volume to racial disparity in post
      procedure in-hospital mortality. RESULTS: Black and Hispanic patients were more
      likely than white patients to receive cardiovascular procedures in low-volume
      hospitals. Black patients had greater risk-adjusted mortality than white patients
      after elective AAA repair (odds ratio [OR], 1.84; 95% confidence interval [CI],
      1.20 to 2.84), CABG (OR, 1.19; 95% CI, 1.06 to 1.33), and CEA (OR, 1.56; 95% CI,
      1.07 to 2.27), but not PTCA. Hispanic patients did not have higher risk-adjusted
      mortality than white patients. Adjusting for hospital volume did not
      substantially reduce the relative risk of death for black patients compared with
      white patients. CONCLUSIONS: Black and Hispanic patients were more likely to
      receive cardiovascular procedures in low-volume hospitals, but hospital volume
      did not explain a large proportion of racial differences in post-procedure
      mortality. Additional research is needed to determine why black patients have
      increased mortality after cardiovascular procedures and how these mortality rates
      can be reduced.

PMID- 16412872
TI  - Racial disparities in cardiovascular procedure outcomes: turn down the volume.

PMID- 16412873
TI  - The year in valvular heart disease.

PMID- 16412874
TI  - Patent foramen ovale: innocent or guilty? Evidence from a prospective population
      based study.
AB  - OBJECTIVES: We sought to determine the association between patent foramen ovale
      (PFO), atrial septal aneurysm (ASA), and stroke prospectively in a unselected
      population sample. BACKGROUND: The disputed relationship between PFO and stroke
      reflects methodologic weaknesses in studies using invalid controls, unblinded
      transesophageal echocardiography examinations, and data that are unadjusted for
      age or comorbidity. METHODS: The use of transesophageal echocardiography to
      identify PFO was performed by a single echocardiographer using standardized
      definitions in 585 randomly sampled, Olmsted County (Minnesota) subjects age 45
      years or older participating in the Stroke Prevention: Assessment of Risk in a
      Community (SPARC) study. RESULTS: A PFO was identified in 140 (24.3%) subjects
      and ASA in 11 (1.9%) subjects. Of the 140 subjects with PFO, 6 (4.3%) had an ASA;
      of the 437 subjects without PFO, 5 had an ASA (1.1%, two-sided Fisher exact test,
      p = 0.028). During a median follow-up of 5.1 years, cerebrovascular events
      (cerebrovascular disease-related death, ischemic stroke, transient ischemic
      attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO
      was not a significant independent predictor of stroke (hazard ratio 1.46, 95%
      confidence interval 0.74 to 2.88, p = 0.28). The risk of a cerebrovascular event
      among subjects with ASA was nearly four times higher than that in those without
      ASA (hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p = 0.074).
      CONCLUSIONS: These prospective population-based data suggest that, after
      correction for age and comorbidity, PFO is not an independent risk factor for
      future cerebrovascular events in the general population. A larger study is
      required to test the putative stroke risk associated with ASA.

PMID- 16412875
TI  - Patent foramen ovale, guilty but only as a gang member and for a lesser crime.

PMID- 16412876
TI  - The Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT)
      trial.
AB  - OBJECTIVES: The purpose of the SCANDSTENT study was to evaluate the use of
      sirolimus-eluting stents (SES) in complex coronary lesions. BACKGROUND: The use
      of SES improves angiographic and clinical outcomes compared with bare-metal
      stents (BMS) in simple coronary artery lesions, but there is limited evidence of
      their safety and efficacy when implanted in complex lesions. METHODS: We randomly
      assigned 322 patients with symptomatic complex coronary artery disease to receive
      either SES or BMS. The lesions were occluded (36%), bifurcational (34%), ostial
      (22%), or angulated (8%) in morphology. The primary end point was the difference
      in minimal lumen diameter six months after stent implantation. RESULTS: The
      patients were well matched in terms of demographic and angiographic baseline
      characteristics; 18% had diabetes. The reference vessel diameter was 2.86 mm in
      mean, and the lesion length 18.0 mm. At follow-up, patients who received SES had
      a minimal lumen diameter of 2.48 mm compared with 1.65 mm in those who received
      BMS (p < 0.001), a diameter stenosis of 19.3% versus 43.8% (p < 0.001), and 2.0%
      versus 31.9% developed restenosis (p < 0.001). The rate of major adverse cardiac
      events was 4.3% with SES versus 29.3% with BMS (p < 0.001), and stent thrombosis
      was observed in 0.6% in the SES group versus 3.1% in the BMS group (p = 0.15).
      CONCLUSIONS: The use of SES markedly reduced restenosis and the occurrence of
      major adverse cardiac events in patients with complex coronary artery lesions
      without increasing the risk of stent thrombosis.

PMID- 16412877
TI  - Microvolt T-wave alternans and the risk of death or sustained ventricular
      arrhythmias in patients with left ventricular dysfunction.
AB  - OBJECTIVES: This study hypothesized that microvolt T-wave alternans (MTWA)
      improves selection of patients for implantable cardioverter-defibrillator (ICD)
      prophylaxis, especially by identifying patients who are not likely to benefit.
      BACKGROUND: Many patients with left ventricular dysfunction are now eligible for
      prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has
      been proposed to improve patient selection. METHODS: Our study was conducted at
      11 clinical centers in the U.S. Patients were eligible if they had a left
      ventricular ejection fraction (LVEF) < or =0.40 and lacked a history of sustained
      ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable
      coronary artery disease, or New York Heart Association functional class IV heart
      failure. Participants underwent an MTWA test and then were followed for about two
      years. The primary outcome was all-cause mortality or non-fatal sustained
      ventricular arrhythmias. RESULTS: Ischemic heart disease was present in 49%, mean
      LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 +/- 6 months of
      follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular
      arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests,
      the hazard ratio for the primary end point was 6.5 at two years (95% confidence
      interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was
      97.5% at two years. The strong association between MTWA and the primary end point
      was similar in all subgroups tested. CONCLUSIONS: Among patients with heart
      disease and LVEF < or =0.40, MTWA can identify not only a high-risk group, but
      also a low-risk group unlikely to benefit from ICD prophylaxis.

PMID- 16412879
TI  - Removal of iodine contrast from coronary sinus in swine during coronary
      angiography.

PMID- 16412878
TI  - Impact of adenosine diphosphate and calcium chelation on platelet aggregation
      testing in patients receiving clopidogrel therapy.

PMID- 16412880
TI  - Effects of N-3 fatty acids on postoperative atrial fibrillation following
      coronary artery bypass surgery.

PMID- 16412881
TI  - Serum erythropoietin levels and infarct size.

PMID- 16412884
TI  - Restenosis, statistics, and reasonable inferences.

PMID- 16412886
TI  - Intravascular ultrasound analysis of polymer-based paclitaxel-eluting stents.

PMID- 16412889
TI  - Late intraocular lens dislocation.

PMID- 16412888
TI  - AHA/ACCF scientific statement on the evaluation of syncope: from the American
      Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing,
      Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and
      Outcomes Research Interdisciplinary Working Group; and the American College of
      Cardiology Foundation In Collaboration With the Heart Rhythm Society.

PMID- 16412890
TI  - Ectasia following laser in situ keratomileusis.

PMID- 16412891
TI  - Keratoconus and corneal ectasia after LASIK.

PMID- 16412892
TI  - Stereopsis in bilaterally pseudophakic patients.

PMID- 16412894
TI  - Advantages of the scleral incision in pediatric cataract surgery.

PMID- 16412896
TI  - Evaluation of biofilm formation on nylon sutures removed from clinically
      noninfected eyes after cataract surgery.

PMID- 16412898
TI  - Should the pupil be used as a fixed reference for instrument alignment?

PMID- 16412899
TI  - Laser iridoplasty for congenital ectopic pupils.

PMID- 16412900
TI  - Choroidal neovascularization after LASIK in a patient with low myopia.

PMID- 16412901
TI  - Phakic IOL implantation versus clear lens extraction in highly myopic eyes.

PMID- 16412902
TI  - Relationship between anterior capsule contraction and posterior capsule
      opacification after cataract surgery in patients with diabetes mellitus.

PMID- 16412903
TI  - Consultation section. Refractive surgical problem.

PMID- 16412914
TI  - Iris reconstruction with a multipiece endocapsular prosthesis in iridocorneal
      endothelial syndrome.
AB  - Iris reconstruction in cases of iridocorneal endothelial (ICE) syndrome is
      extremely challenging because of the nature of the iris tissue, which is
      typically friable and poorly suited to suture repair. Reconstruction in such
      cases often requires artificial iris implantation. This report illustrates
      cataract extraction and iris reconstruction with a multipiece endocapsular iris
      prosthesis that can be inserted through a small incision. Maintenance of a small
      incision size is a distinct advantage when glaucoma is coexistent in patients
      with ICE syndrome. It also demonstrates the presence of an ICE membrane over the
      anterior capsule and the importance of recognizing this membrane rather than
      confusing it with the anterior capsule when performing the capsulorhexis.

PMID- 16412915
TI  - Stabilization of anterior chamber depth during phacoemulsification cataract
      surgery in vitrectomized eyes.
AB  - Abnormal fluctuations in anterior chamber (AC) depth including deepening and
      mydriasis with paradoxical shallowing and miosis have been described during
      phacoemulsification cataract surgery in previously vitrectomized eyes.
      Contributory factors include zonular laxity and reduction of vitreous volume.
      This report describes a technique to stabilize AC depth and allow safer sculpting
      and removal of lens matter.

PMID- 16412916
TI  - Surgeon offsets and dynamic eye movements in laser refractive surgery.
AB  - PURPOSE: To determine the amount of static and dynamic pupil decentrations that
      occur during laser refractive surgery. SETTING: The Center of Visual Science and
      the Department of Ophthalmology, University of Rochester, Rochester, New York,
      USA. METHODS: The surgeon's accuracy in aligning the pupil center with the laser
      center axis was measured when engaging the eye-tracker in 17 eyes receiving
      conventional laser in situ keratomileusis (LASIK) procedures (Technolas 217z;
      Bausch & Lomb). Eye movements were measured subsequently during the treatment in
      10 eyes using a pupil camera operating at 50 Hz. Temporal power spectra were
      calculated from the eye movement measurements. RESULTS: The mean pupil
      misalignment by the surgeon at the beginning of the procedure was 206.1 microm +/
      80.99 (SD) (with respect to the laser center). The laser center was typically
      misaligned below (inferiorly) and to the left (nasally and temporally in left and
      right eyes, respectively) of the pupil [corrected] center. Small amounts of
      cyclotorsion were observed during the ablation (<2 degrees). The mean magnitude
      of dynamic pupil decentration from the laser center during treatment was 227.0 +/
      44.07 microm. The mean standard deviation of eye movements was 65.7 +/- 25.64
      microm. Temporal power spectra calculated from the horizontal and vertical
      changes in eye position during the ablation were similar. Ninety-five percent of
      the total power of the eye movements was contained in temporal frequencies up to
      1 Hz, on average, in both directions. CONCLUSIONS: Most eye movements during
      LASIK are slow drifts in fixation. An eye-tracker with a 1.4 Hz closed-loop
      bandwidth could compensate for most eye movements in conventional or customized
      ablations.

PMID- 16412917
TI  - Effect of anterior capsule polishing on posterior capsule opacification and
      neodymium:YAG capsulotomy rates: three-year randomized trial.
AB  - PURPOSE: To compare the long-term effect of extensive polishing and nonpolishing
      of the anterior lens capsule on posterior capsule opacification (PCO) and
      neodymium:YAG (Nd:YAG) capsulotomy rates. SETTING: Department of Ophthalmology,
      Medical University of Vienna, Vienna, Austria. METHODS: This prospective
      randomized bilateral double-masked study included 108 eyes of 54 consecutive
      patients with age-related cataract. Following phacoemulsification, 3-piece
      intraocular lenses (IOLs) with round-edged silicone optics were implanted.
      Patients received an Allergan SI-40 IOL with a truncated, round optic edge or a
      Domilens Silens6 IOL with a fully round optic edge. Patients were randomly
      assigned to have extensive anterior capsule polishing with the Menapace
      aspiration curette or no treatment in the first eye; the second eye received the
      opposite treatment. Digital retroillumination images were taken at 1 week, 1
      year, and 3 years, and Nd:YAG capsulotomy rates were evaluated. Posterior capsule
      opacification was objectively scored using automated image analysis software
      (AQUA) or estimated based on clearly defined assumptions if a capsulotomy had
      been performed. RESULTS: Thirty-nine patients (78 eyes) concluded the study.
      Three-year PCO scores after polishing did not differ significantly (P>.05).
      However, 21 polished eyes (53.8%) required Nd:YAG laser capsulotomy compared with
      14 nonpolished eyes (35.9%). The mismatch between PCO scores and Nd:YAG rates
      resulted from a change in PCO morphology that is not detected by scoring methods
      based on retroillumination photography but is visually disturbing to patients.
      CONCLUSIONS: Polishing the anterior capsule was effective in reducing fibrotic
      opacification but ineffective in reducing regeneratory opacification. Changes in
      regeneratory PCO morphology not picked up by retroillumination photography
      increased the need for Nd:YAG laser capsulotomy.

PMID- 16412918
TI  - Contrast sensitivity function in eyes with diffractive bifocal intraocular
      lenses.
AB  - PURPOSE: To evaluate the image quality of asymmetric Acri. Twin bifocal
      intraocular lenses (IOLs) (Acri.Tec) by comparing distance and near black-white
      contrast sensitivity function with that of the Pharmacia 811E IOL. SETTING:
      Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
      METHODS: Thirty-two eyes of 16 patients were examined after contralateral
      implantation of 1 Acri. Twin near-weighted 733D IOL and 1 Acri. Twin distance
      weighted 737D IOL. Twenty eyes in 10 patients were examined after binocular
      Pharmacia 811E IOL implantation. Best corrected distance and near visual acuities
      were determined. Individual reading distance was recorded and corrected to 40 cm
      for the near contrast test (Holladay Contrast Acuity Test). Distance contrast
      sensitivity function was evaluated using the Acuity Max (Science 2020) computer
      program. RESULTS: Best corrected distance visual acuity was significantly better
      in patients with the 737D IOL than in those with the 733D or 811E IOLs. For
      distance reading with best distance correction, the 733D IOL performed better
      than the 737D and the 811E. Individual reading distance with the Acri. Twin IOL
      and 811E IOL was 33.6 cm and 34.0 cm, respectively. Best distance-corrected near
      contrast sensitivity function was better in eyes with the near-weighted 733D IOL.
      Binocular testing showed a significant difference between the 2 groups only at
      low-contrast values. At distance, contrast sensitivity function was better with
      the 737D IOL, whereas no difference was found between the 733D and the 811E IOLs.
      Binocular contrast sensitivity function at distance revealed statistically
      significantly better results in the Acri. Twin group. CONCLUSION: An asymmetric
      diffractive bifocal lens system was advantageous in terms of vision quality when
      implanted binocularly and superior to monocular stronger weighted focus compared
      with conventional bifocal IOLs.

PMID- 16412920
TI  - Blue-light filtering intraocular lens in patients with diabetes: contrast
      sensitivity and chromatic discrimination.
AB  - PURPOSE: To evaluate potential changes in contrast sensitivity and color
      discrimination in diabetic patients who had cataract surgery and implantation of
      the blue-light filtering AcrySof Natural (SN60AT) intraocular lens (IOL) compared
      with an ultraviolet-only filtering (AcrySof SA60AT) IOL. SETTING: Refractive
      Surgery Unit, Hospital NISA Valencia al Mar, Valencia, Spain. METHODS: Forty-four
      eyes of 22 diabetic patients were enrolled in a blue-light filtering fellow-eye
      control study. Patients received yellow-tinted IOLs (AcrySof Natural) in 1 eye
      and non-yellow-tinted IOLs (AcrySof SA60AT) in the fellow eye. Three months after
      surgery, monocular contrast sensitivity function was measured with the CSV 1000-E
      contrast sensitivity chart at distance and color discrimination was tested with
      the Farnsworth-Munsell 100-hue test. RESULTS: Eyes implanted with the blue-light
      filtering IOLs showed better contrast sensitivity values than fellow eyes
      implanted with non-yellow-tinted IOLs (P<.05). The blue-light filtering IOL did
      not modify chromatic discrimination compared with the non-yellow-tinted IOL (P =
      .62). In the blue-yellow axis discrimination study, the eyes implanted with the
      AcrySof Natural IOL had statistically significant better color vision (P = .008).
      CONCLUSIONS: In diabetic patients, the AcrySof Natural IOL provides better
      contrast sensitivity than the AcrySof SA60AT. The blue-light filter of the
      AcrySof Natural IOL did not cause chromatic discrimination defects based on total
      error scores and improved color vision in the blue-yellow chromatic axis in
      diabetic patients.

PMID- 16412919
TI  - Posterior corneal surface changes after hyperopic laser in situ keratomileusis.
AB  - PURPOSE: To evaluate posterior corneal surface topographic changes after
      hyperopic laser in situ keratomileusis (H-LASIK) using Orbscan I (Orbtek, Inc.).
      SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan.
      METHODS: In 25 eyes of 15 patients who had H-LASIK, the posterior corneal surface
      was measured with slit-scanning corneal topography (Orbscan I) preoperatively and
      1 year postoperatively. The center as a fit zone and calculated posterior corneal
      surface changes were taken at 4 points: nasal, temporal, superior, and inferior
      sides in the 5.0 mm diameter. The posterior corneal topographic changes were
      analyzed using an analysis of variance. The postoperative:preoperative
      magnification ratio of the posterior corneal surface was calculated in a
      theoretical eye model. RESULTS: When a "+" reading was defined as the forward
      displacement and "-" was defined as the backward displacement, the mean posterior
      corneal topographic changes were -2.8 microm +/- 27.9 (SD) at the nasal side, 
      4.5 +/- 27.8 microm at the temporal side, -3.9 +/- 20.1 microm at the superior
      side, and -2.3 +/- 20.1 microm at the inferior side. The posterior corneal
      surface between any 2 examined points showed no significant difference after H
      LASIK. In addition, the hypothetical change in the posterior cornea was -8.3
      microm after +3.0 diopter H-LASIK, which was approximately closer to the study
      results. In each side, the amount of the attempted correction was significantly
      correlated with the posterior corneal topographic change. CONCLUSIONS: Clinical
      measurement of the posterior corneal displacement after H-LASIK with Orbscan
      revealed a backward shift. This change corresponded to the hypothetical
      artifactual changes with Orbscan; that is, changes in the magnification ratio.

PMID- 16412921
TI  - Laser in situ keratomileusis outcomes following radial keratotomy, astigmatic
      keratotomy, photorefractive keratectomy, and penetrating keratoplasty.
AB  - PURPOSE: To evaluate the safety and efficacy of laser in situ keratomileusis
      (LASIK) to enhance refractive status following other corneal surgical procedures.
      SETTING: Clinical office-based practice. METHODS: Seventy-one eyes of 57 patients
      had LASIK for refractive errors following radial keratotomy (n = 22), astigmatic
      keratotomy (n = 13), photorefractive keratectomy (n = 18), and penetrating
      keratoplasty (n = 18). A Moria LSK-1 microkeratome was used with a Visx S2 or
      Wavelight Allegretto excimer laser. Data were acquired by retrospective chart
      review of all appropriately qualified patients. RESULTS: The mean preoperative
      manifest refractive spherical equivalent (MRSE) was -3.93 diopters (D) +/- 2.83
      (SD) in myopic eyes and +1.43 +/- 1.79 D in hyperopic eyes. The mean time from
      the initial corneal surgical procedure to LASIK was 65.0 months. The mean post
      LASIK follow-up was 9.40 months (range 1 to 42 months). Postoperatively, the mean
      MRSE was -0.85 +/- 1.42 D in myopic eyes (P<.0001) and -0.16 +/- 1.09 D in
      hyperopic eyes (P<.0001). Enhancement by LASIK was required in 14% of eyes.
      CONCLUSION: In eyes that have had a variety of previous corneal surgeries, LASIK
      offers a safe and predictable method for enhancing refractive results.

PMID- 16412922
TI  - Refractive results with secondary piggyback implantation to correct pseudophakic
      refractive errors.
AB  - PURPOSE: To assess the efficacy and safety of implanting a second intraocular
      lens (IOL) to correct pseudophakic refractive errors. SETTING: Goldschleger Eye
      Institute, Sheba Medical Center, Tel Hashomer, Israel. METHODS: This prospective
      noncomparative case series included 10 pseudophakic eyes, 5 with a myopic
      residual refractive error and 5 with a hyperopic residual refractive error. All
      eyes had secondary piggyback IOL implantation with the IOL placed in the ciliary
      sulcus. Five types of IOLs were used to correct the residual refractive error.
      RESULTS: The mean preoperative myopia was -6.6 diopters +/- 3.3 (SD), and the
      refractive outcome was within 0.5 +/- 0.7 D of the desired refraction (range -1.5
      [undercorrected] and +1.0 D [overcorrected]). The mean preoperative hyperopia was
      +3.8 +/- 0.8 D, and the refractive outcome was within 0.46 +/- 0.4 D of the
      desired refraction (range 0 and 1.0 D overcorrected). All patients showed visual
      acuity improvement. Best spectacle-corrected visual acuity improved from 20/44 to
      20/30 (P<.05). CONCLUSION: An IOL type that is appropriate for implantation in
      the ciliary sulcus is a viable option for correcting pseudophakic refractive
      error using the piggyback technique.

PMID- 16412923
TI  - Excimer laser surgery for correction of ametropia after cataract surgery.
AB  - PURPOSE: To review the cases of patients who had excimer laser refractive surgery
      to correct unintentional or undesired ametropia after cataract extraction with
      intraocular lens (IOL) implantation. SETTING: Wilmer Laser Vision Correction
      Center, Wilmer Eye Institute, Baltimore, Maryland, USA. METHODS: In this
      retrospective noncomparative review of consecutive cases, the Wilmer Laser Vision
      Correction Center's database was searched for patients who had laser in situ
      keratomileusis or photorefractive keratectomy to correct ametropia after cataract
      extraction with IOL implantation. RESULTS: Using the Visx Star excimer laser
      system (Visx, Inc.), 11 procedures were performed in 11 eyes of 10 patients a
      mean of 47 months (range 2 to 216 months) after cataract extraction with IOL
      implantation. Except for 1 patient with a silicone plate lens, all patients
      received 3-piece poly(methyl methacrylate) lenses. The mean age at time of
      excimer treatment was 75 years (range 70 to 81 years). Before laser surgery, the
      mean spherical equivalent of patient eyes was -3.76 diopters (D) +/- 2.50 (SD)
      (range -6.50 to +0.75 D), spherical refraction ranged from -9.00 D to plano, and
      the highest cylindrical refraction was +5.50 D. At last follow-up (mean 12.2
      months; range 1 to 38 months), the mean manifest spherical equivalent was -0.88
      +/- 1.43 D (range -2.75 to +2.13 D). Changes in mean manifest spherical
      equivalent were highly significant (P = .03, Wilcoxon signed rank test for paired
      values). There was no difference between targeted and achieved postoperative
      refraction (P = .34, Wilcoxon test). Increasing age was correlated with a
      hyperopic shift (r = 0.525, P = .05). All patients were satisfied with their
      final uncorrected visual acuity (UCVA), which improved in every case. Except for
      1 patient in whom an epiretinal membrane developed, best spectacle-corrected
      visual acuity remained unchanged or improved. CONCLUSIONS: In this series of
      patients, who were a few decades older than the typical excimer laser candidate,
      laser refractive surgery was a safe, effective, and predictable method to correct
      ametropia after cataract extraction with IOL implantation. It may be a viable,
      noninvasive alternative to intraocular surgery, which has potential
      complications. Although satisfactory for all patients, final UCVA was not as high
      as that reported in laser refractive surgery patients in general, and this result
      may be because of prior cataract extraction with IOL implantation or increased
      age.

PMID- 16412924
TI  - Discriminative power of reading tests to differentiate visual impairment caused
      by cataract and age-related macular degeneration.
AB  - PURPOSE: To determine whether preoperative reading tests can be used for
      differentiating visual impairments with regard to the diagnosis of cataract and
      age-related macular degeneration (ARMD). SETTING: Department of Ophthalmology,
      Medical University of Vienna, Vienna, Austria. METHODS: Reading performance of
      patients with nuclear cataract, posterior subcapsular cataract, and ARMD were
      evaluated with respect to reading acuity, maximum reading speed, and critical
      print size; normal-sighted participants were tested as controls. A multivariate
      discriminant analysis of the 4 groups (100 eyes of 100 participants) was
      performed to evaluate how many patients could be correctly diagnosed by
      significant differences in the tested reading parameters. Subsequently, the
      nuclear cataract and posterior subcapsular cataract patients were compared with
      cataract patients with coexisting ARMD. RESULTS: Distance visual acuity was
      comparable in the nuclear cataract, posterior subcapsular cataract, and ARMD
      groups (P>.05). Reading acuity was significantly reduced in posterior subcapsular
      cataract and ARMD patients compared with nuclear cataract patients and controls
      (P<.0001). No significant difference in maximum reading speed was found between
      the nuclear cataract patients and the controls (P = .07), whereas the maximum
      reading speed of the posterior subcapsular cataract and ARMD patients was
      significantly reduced (P<.0001). In the discriminant analysis, it was possible to
      assign the correct diagnosis to 72% of the nuclear cataract patients, 76% of the
      posterior subcapsular cataract patients, 72% of the ARMD patients, and 92% of the
      controls. Comparing the reading performance of nuclear cataract and posterior
      subcapsular cataract patients and cataract patients with coexisting ARMD showed
      that reading performance was significantly impaired in the comorbid patients
      (nuclear cataract and ARMD, P<.001; posterior subcapsular cataract and ARMD,
      P<.05). CONCLUSION: The high discriminant accuracy shows that this standardized
      reading test system is a valuable diagnostic tool for evaluating functional
      visual impairments when distance visual acuity alone cannot elucidate the origin
      of functional impairment. Considering the significant discrepancies in reading
      performance among patients with nuclear cataract, posterior subcapsular cataract,
      and ARMD, reading tests may relevantly improve the clinical evaluation of
      patients with visual loss, even of patients with ocular comorbidity.

PMID- 16412925
TI  - Long-term changes in the morphology of posterior capsule opacification.
AB  - PURPOSE: To classify the morphologic appearance of posterior capsule
      opacification (PCO) and to observe and document the changes over longer periods
      of time. SETTING: Department of Ophthalmology, Medical University of Vienna,
      Vienna, Austria. METHODS: Eighty-one pseudophakic eyes of 53 patients with PCO of
      varying degrees were included in this prospective study. Digital
      retroillumination images of the posterior capsule were taken in a standardized
      fashion 1, 2, and 3 years after cataract surgery. The PCO morphology was
      classified, and changes among the 3 follow-up images were analyzed. RESULTS: At
      1, 2, and 3 years, pearls occurred in 16 (20%), 41 (51%), and 57 (63%) eyes.
      Pearls increased in size and number. Cases with thin layers of PCO decreased from
      53 to 33 to 16 eyes. Conversely, cases with thick layers increased from 18 to 45
      and 64 eyes. "Cheese holes" appeared most frequently as the predominant structure
      (range 47% to 51%), followed by plates (range 28% to 31%), islands (range 15% to
      20%), and traces of PCO (range 1% to 5%). Changes in expansion of the PCO area
      were observed in 61 eyes (75%) during period 1 (1 to 2 years) and period 2 (2 to
      3 years). Regions of expansion and regression in the same eye occurred in periods
      1 and 2 in 11 eyes (14%) and 9 eyes (11%), respectively. The phenomenon of
      thinning bridges, a regression of syncytial extensions of PCO, occurred in 22
      eyes (27%) and 32 eyes (40%), respectively. An overlapping growth of 2 layers was
      observed in 18 eyes (22%). CONCLUSIONS: The morphology of PCO is multifaceted.
      Apart from the Elschnig pearls, categories such as cheese holes, plates, islands,
      and traces of PCO were distinguished. Over the years, pearls increased in
      frequency, size, and number. Expansion and regression occurred simultaneously in
      some cases. Two or more layers grew on top of each other in some eyes.

PMID- 16412926
TI  - Comparison of Colvard pupillometer and infrared digital photography for
      measurement of the dark-adapted pupil diameter.
AB  - PURPOSE: To investigate the accuracy of pupil diameter measurement using the
      Colvard pupillometer and to determine the learning curve for inexperienced
      examiners. SETTING: Texas Tech University Health Sciences Center, Lubbock, Texas,
      USA. METHODS: In this population study, subjects with normal pupillary behavior
      were tested by 1 of 2 investigators (examiner A, examiner B). After 5 minutes of
      dark adaptation at 1 lux, digital infrared pupil photography of the right eye was
      performed, followed by measurement of the horizontal pupil diameter and vertical
      pupil diameter with the Colvard pupillometer. The photographs were digitally
      analyzed to determine the horizontal and vertical pupil diameters. During phase I
      of the study, examiners were masked to the results of infrared pupil photography;
      during phase II, they reviewed the infrared pupil photography results after each
      testing session. Bland-Altman plots were created to detect measurement bias;
      results were graphed by subject test sequence to assess learning. A test
      difference of less than +/-0.5 mm was considered clinically acceptable. RESULTS:
      Fifty-nine subjects were tested in phase I, of whom 39 had adequate infrared
      pupil photography for analysis; 40 were tested in phase II, of whom 34 were
      included. The mean age of the analyzed subjects was 27 years (range 18 to 44
      years). For all subjects, the infrared pupil photography median horizontal pupil
      diameter was 7.09 mm +/- 0.75 (SD) (range 5.44 to 8.79 mm); the median vertical
      pupil diameter was 7.22 +/- 0.79 mm (range 5.45 to 9.10 mm). Examiner A initially
      had a negative bias (Colvard pupillometer value less than infrared pupil
      photography value) for both horizontal and vertical pupil diameter measurements,
      which resolved during phase I after 23 subjects were tested; 18 of the final 19
      subjects tested (11 phase I, 8 phase II) showed a test difference of less than
      0.5 mm for all readings. The pupil diameter did not affect the bias. Examiner B
      had a strong positive bias that persisted throughout the study. Testing 26
      subjects in 5 sessions during phase II did not improve the accuracy. During the
      final testing session, 3 of 8 subjects had a test difference of 0.5 mm or more in
      at least 1 dimension. The pupil diameter did not affect the bias. CONCLUSION: The
      Colvard pupillometer is susceptible to user errors causing unidirectional bias
      and seems to have a steep and variable learning curve.

PMID- 16412927
TI  - Shallow ablations in phototherapeutic keratectomy: long-term follow-up.
AB  - PURPOSE: To evaluate the long-term efficacy and safety of shallow ablations in
      phototherapeutic keratectomy (PTK) in patients with recurrent corneal erosions.
      SETTING: Department of Ophthalmology, Tuen Mun Hospital, Hong Kong, China.
      METHODS: A retrospective analysis of 13 consecutive eyes with recurrent corneal
      erosions treated by PTK from 1997 to 1999 was performed. All eyes failed to
      respond to conventional treatments, and all eyes had corneal erosions involving
      the visual axis. Outcome measures included number of recurrences, change in best
      corrected visual acuity (BCVA) and spherical equivalent (SE), and complications
      arising from the laser treatment. RESULTS: Indications for PTK were recurrent
      corneal erosions secondary to minor abrasive trauma (9 eyes) and map-dot
      fingerprint corneal dystrophy (4 eyes). The mean ablation depth was 4.6 microm
      (range 3.4 to 5.8 microm). Mean postoperative follow-up was 49.5 months (range 24
      to 68 months). The overall success rate after only 1 treatment was 84.6%. Eleven
      of 13 eyes had a preserved or improved BCVA, while 2 eyes showed deterioration of
      1 line on Snellen testing. Seven of 13 patients had no change in SE; the rest had
      a change of less than +/-0.50 diopters. There were no major complications.
      CONCLUSIONS: The comparable success rate after a single treatment suggests that
      PTK may still be effective at a shallower depth than previously considered.
      Shallow ablations may have lower chances of complications associated with deeper
      ablations. Further studies involving a larger number of subjects are warranted.

PMID- 16412928
TI  - Effect of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions on human
      corneal epithelium following 2 dosing regimens.
AB  - PURPOSE: To determine whether gatifloxacin 0.3% ophthalmic solution or
      moxifloxacin 0.5% ophthalmic solutions are toxic to the corneal epithelium when
      used with 1 of 2 dosing regimens in healthy human eyes. SETTING: Price Vision
      Group, Indianapolis, Indiana, USA. METHODS: In this double-masked randomized
      fellow-eye comparison study, gatifloxacin 0.3% was instilled in 1 eye and
      moxifloxacin 0.5% in the other eye either 4 times a day for 7 days or hourly for
      10 hours. Before and after dosing, all eyes were examined with a slitlamp and the
      cell layers in the central cornea were evaluated by confocal microscopy. Subject
      discomfort with study drop instillation was also assessed. RESULTS: There was no
      statistically significant increase in the incidence or severity of superficial
      punctuate keratitis following use of gatifloxacin 0.3% or moxifloxacin 0.5% when
      instilled 4 times a day for 7 days or hourly for 10 hours. Hourly use of
      gatifloxacin 0.3% for 10 hours resulted in a mild but statistically significant
      increase in conjunctival hyperemia (P = .029). Use of moxifloxacin 0.5% resulted
      in a small but statistically significant deterioration of the corneal epithelial
      surface as assessed by confocal microscopy (P = .045). The incidence of subject
      discomfort with study drop instillation was comparable for the 2 antibiotics (P =
      .67). CONCLUSION: Use of ophthalmic solutions of gatifloxacin 0.3% or
      moxifloxacin 0.5% did not result in clinically significant epithelial toxicity in
      healthy human corneas after dosing regimens of 4 times a day for 7 days or hourly
      for 10 hours dosing regimens.

PMID- 16412929
TI  - Determination of aqueous and vitreous concentration of moxifloxacin 0.5% after
      delivery via a dissolvable corneal collagen shield device.
AB  - PURPOSE: To determine the penetration of moxifloxacin 0.5% in the human aqueous
      and vitreous when delivered by a presoaked collagen shield. SETTING: University
      based clinical practice. METHODS: Moxifloxacin 0.5% was administered before
      vitrectomy surgery in 10 patients using a 24-hour dissolvable cross-linked
      corneal collagen shield delivery device. Aqueous and vitreous samples were
      obtained after the shield was placed for 4 hours in the first 5 patients and for
      24 hours in the second 5 patients. Assays were performed using high-performance
      liquid chromatography. RESULTS: Delivery of moxifloxacin via a collagen shield
      revealed a mean aqueous concentration of 0.30 microg/mL +/- 0.17 (SD) 4 hours
      after placement (n = 5). Vitreous levels at 4 hours and aqueous and vitreous
      levels at 24 hours were negligible using this route of administration. Peak
      aqueous moxifloxacin levels occurred soon after shield placement. This is when
      high concentrations of moxifloxacin are most needed to clear the aqueous of
      bacteria. The minimum inhibitory concentration at which 90% of the isolates were
      inhibited for organisms commonly responsible for endophthalmitis was exceeded in
      the 4-hour aqueous group. Negligible concentrations were detected at 24 hours.
      CONCLUSIONS: Although aqueous moxifloxacin levels achieved through the use of a
      collagen shield delivery device are lower than via topical drops, there are
      several advantages to this route of delivery that make it appealing in the
      immediate postoperative period. Future studies will be needed to define precisely
      the role of fourth-generation fluoroquinolones and presoaked collagen shields in
      the prophylaxis or management of intraocular infections.

PMID- 16412930
TI  - Phacofragmentation with perfluorocarbon liquid and anterior chamber or scleral
      fixated intraocular lens implantation for the management of luxated crystalline
      lenses.
AB  - PURPOSE: To present a complex surgical technique used for the management of
      luxated crystalline lenses and evaluate treatment results. SETTING: Department of
      Ophthalmology, Medical University of Lodz, Lodz, Poland. METHODS: This
      prospective study involved 29 consecutive patients (30 eyes) with the mean age of
      60.3 years. The applied surgical technique comprised pars plana vitrectomy,
      perfluorocarbon liquid injection, and crystalline lens phacofragmentation in the
      vitreous cavity. Simultaneously, anterior chamber intraocular lenses (IOLs) were
      implanted in 10 eyes, and scleral-fixated posterior chamber IOLs in 20 eyes. The
      follow-up mean was 5.2 month (range 1 to 16 months). RESULTS: No complications
      were observed during phacofragmentation. Visual acuity improved in 22 cases and
      did not change in the other 8 eyes. The mean visual acuity was 0.40 +/- 0.37 (SD)
      (range between hand movements and 1.0) preoperatively and 0.68 +/- 0.34 (range
      0.05 to 1.0) postoperatively. In 22 cases (73%), very good or good visual acuity
      (6/6 to 6/12) was achieved. There were no intraoperative complications.
      Postoperatively, transient hypotony was observed in 10 eyes, fibrinous reaction
      in the anterior chamber in 1 eye, dispersed blood in the vitreous cavity in 8
      eyes, hyphema in 1 eye, corneal edema in 1 eye, vitritis in 3 cases, iris tug in
      1 eye with an anterior chamber IOL, and slight dislocation of the scleral-fixated
      IOL in 1 case. Intraocular pressure was elevated in 11 eyes preoperatively;
      postoperatively, it normalized in 7 eyes without medication. CONCLUSION:
      Phacofragmentation with perfluorocarbon liquid and IOL implantation for the
      management of luxated crystalline lenses was safe and effective method, providing
      good functional results.

PMID- 16412931
TI  - Comparison of higher-order wavefront aberrations with 3 aberrometers.
AB  - PURPOSE: To evaluate the agreement of higher-order aberrations (HOAs) between
      aberrometers based on the Hartmann-Shack wavefront technology. SETTING:
      Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan.
      METHODS: Three clinical aberrometers WaveScan (Visx Inc.), LADARWave (Alcon
      Inc.), and Zywave (Bausch & Lomb Inc.) were used to measure HOAs in 34
      cycloplegic eyes in 17 subjects. All the measurements in each subject were
      performed in 1 visit to reduce the impact of biologic fluctuation of HOAs. Each
      device was operated by an independent experienced operator, and the operators
      were blind to the data obtained from the other aberrometers. Root mean square
      (RMS) of coma, spherical aberration, and total 3rd- and 4th-order HOAs were
      compared between any 2 devices by a paired t test. RESULTS: WaveScan had the
      lowest mean RMS, whereas Zywave reported the highest mean RMS for any HOAs. The
      coefficients of variation were similar between any 2 devices. Paired t tests of
      RMS yielded a P value <.01 in 9 of 12 comparisons. In general, the largest
      discrepancies of HOA measures were between WaveScan and Zywave, and similar data
      were found between LADARWave and WaveScan. More than 80% of the absolute
      difference of HOA RMS between LADARWave and WaveScan, 50% to 78% between
      LADARWave and Zywave, and 38% to 59% between WaveScan and Zywave were within +/
      0.1 microm. CONCLUSIONS: Significant discrepancies in HOA measurements were found
      among the 3 popular aberrometers. The HOA RMS data were closer between LADARWave
      and WaveScan, and HOA RMS by Zywave was generally higher than the other 2
      devices. The 3 devices had comparable measurement variation.

PMID- 16412932
TI  - Clinical evaluation of endothelial cell decrease with VisThesia in
      phacoemulsification surgery.
AB  - PURPOSE: To assess the endothelial cell decrease after the use of sodium
      hyaluronate 0.3% and lidocaine hydrochloride 2% (VisThesia) to determine whether
      the addition of lidocaine 1% to sodium hyaluronate 1.5% makes the solution more
      toxic to the cornea. SETTING: Instituto de Oftalmologia Avanzada, Madrid, Spain,
      and Unita Operative Oculistica, Cesena, Italy. METHODS: VisThesia is an
      ophthalmic viscosurgical device (OVD) that incorporates lidocaine 1% to provide
      better comfort to patients under topical anesthesia. Fifty eyes 50 patients were
      operated on following the same patient selection and surgical technique. After
      the povidone-iodine (Betadine) ocular asepsis, 1 full ampoule of VisThesia
      Topical was applied over the corneal surface. The intracameral product was used
      as a routine OVD during the phacoemulsification procedure. The endothelium of the
      central cornea was examined preoperatively and 3 months after surgery using a
      noncontact endothelium microscope. RESULTS: At the last follow-up visit, the mean
      best corrected visual acuity was 0.88 +/- 0.18 and the mean manifest SE was -0.36
      +/- 1.78 D. The mean endothelial cell density had decreased from 2363.57 +/-
      435.4 cells/mm2 preoperatively to 2222.6 +/- 537.69 cells/mm2 at 3 months. These
      values are comparable with results obtained in other investigations published in
      the literature using other, similar OVD. CONCLUSIONS: The results observed in
      this investigation indicate that the addition of lidocaine to the sodium
      hyaluronate in VisThesia does not induce additional toxicity nor does it result
      in increased endothelial cell loss when compared with other, similar OVDs.

PMID- 16412933
TI  - Age and sex profile of patients having cataract surgery between 1986 and 2003.
AB  - PURPOSE: To investigate the age and sex profile of patients having cataract
      surgery by 2 consulting ophthalmic surgeons over an 18-year period. SETTING:
      Waterford Regional Hospital, Waterford, Republic of Ireland. METHODS: Operating
      theater logbooks were reviewed, and all patients having cataract surgery between
      January 1986 and December 2003 in Waterford Regional Hospital were identified.
      The following data were recorded for each patient: age, sex, and type of cataract
      surgery. Patients having cataract surgery were categorized according to the date
      of the procedure as follows: Group 1: 1986-1991; Group 2: 1992-1997; Group 3:
      1998-2003. RESULTS: Eight thousand two hundred fifty-seven patients who had
      cataract surgery during the study period were identified. The mean age of
      patients was 72.32 years +/- 12.21 (SD) and 74.89 +/- 11.03 years of men and
      women, respectively. The age profile of patients having cataract surgery was
      statistically comparable in Groups 1, 2, and 3 (mean age; Group 1: 72.33 +/-
      13.03 years; Group 2: 73.72 +/- 11.78 years; Group 3: 74.57 +/- 10.69 years),
      indicating that the age profile of patients did not change significantly with the
      passage of time (analysis of variance, F<1). The proportion of women having
      cataract surgery rose significantly over the duration of the study period (1986
      1991: 55.13%; 1992-1997: 57.68%; 1998-2003: 59.43% (chi-square test, P<.01)).
      CONCLUSIONS: The age profile of 8257 patients having cataract surgery did not
      change over the 18-year study period. A small but significant increase in the
      proportion of women having cataract surgery was noted in latter years. This data
      is useful to those involved in health care planning.

PMID- 16412934
TI  - New classification of ophthalmic viscosurgical devices--2005.
AB  - PURPOSE: To revise the generally accepted classification of ophthalmic
      viscosurgical devices (OVDs) to include cohesion data and the new class of
      viscous dispersive OVDs. SETTING: York Finch Eye Associates, Toronto, Ontario,
      Canada, and Alcon Research Limited, Fort Worth, Texas, USA. METHODS:
      Pseudoplasticity and cohesion-dispersion (CDI) data of DisCoVisc (hyaluronic acid
      1.6%-chondroitin sulfate 4%), a new viscous dispersive OVD, were determined and
      compared with existing OVDs. The existing classification of OVDs was unable to
      accommodate its properties, so the classification was modified to include a new
      class and other potential new classes which currently remain unoccupied. RESULTS:
      Current OVD classification, although based on the clinically significant
      rheologic parameters of zero-shear viscosity and cohesion, only uses zero-shear
      viscosity because of the high correlation of these 2 parameters in existing OVDs.
      The appearance of DisCoVisc forces modification of the existing scheme because it
      does not fit into a preexisting category. The new proposed broadened
      classification is changed from a 1-dimensional list into a 2-dimensional table
      and considers CDI independently from viscosity for all OVDs. Expansion of the
      classification of OVDs in this manner predicts further possible new innovative
      OVDs for surgical use. CONCLUSION: The surgical behavior of OVDs can be predicted
      by their position in a classification of OVDs based upon zero-shear viscosity and
      cohesion.

PMID- 16412935
TI  - Evaluating and defining the sharpness of intraocular lenses: part 1: Influence of
      optic design on the growth of the lens epithelial cells in vitro.
AB  - PURPOSE: To develop a new method for the evaluation of the optic edge design of
      intraocular lenses (IOLs). SETTING: Charite Humboldt University and Berlin Eye
      Research Institute (Beri), Berlin, Germany. METHODS: Poly(methyl methacrylate)
      IOLs with 11 edge designs were manufactured. Each lens design was evaluated using
      EPCO 2000. Also, edge's ability to stop cell growth was observed by placing each
      IOL into cell culture and observing cell growth over 18 days on average. RESULTS:
      Only 3 groups, those with the sharpest edge design, prevented the growth of lens
      epithelial cells onto the visual axis of the lens. The edge design that
      effectively stopped cell growth was characterized by an area above the edge of
      13.5 microm2 at the most. CONCLUSION: Results shows that the edge design of IOLs
      plays an important role in the prevention of posterior capsule opacification. A
      specific optic edge design was most effective in this prevention.

PMID- 16412936
TI  - Ultrasound thermal damage to rabbit corneas after simulated phacoemulsification.
AB  - PURPOSE: To determine rabbit cornea thermal tolerance and evaluate the effects of
      ultrasound (US) on this tissue after applying defined US heat doses. SETTING: Eye
      Clinic; Anatomy Histology and Forensic Medicine, University of Florence,
      Florence, Italy. METHODS: Hyperthermia was induced in rabbit corneas using US,
      simulating a phacoemulsification procedure. The US power was set at 100% in
      continuous mode, and temperature values were reached within 10 seconds of the
      onset of US treatment. Corneal surface temperatures were continuously monitored
      and recorded by thermographic registration. The eyes of 16 rabbits were examined:
      4 controls, 8 treated at 40 degrees C for 10 seconds, 8 treated at 50 degrees C
      for 10 seconds, and 12 treated at 60 degrees C for 10 seconds. All 32 corneal
      buttons were removed and prepared for light microscopic evaluation with
      hematoxylin and eosin staining, trichromic staining, and zinc iodide-osmium
      tetroxide solution. The 12 corneas treated at 60 degrees C for 10 seconds were
      also processed for immunohistochemical analysis. RESULTS: Corneas at 40 degrees C
      for 10 seconds were grossly and histologically normal and were not different from
      control corneas. Corneas at 50 degrees C for 10 seconds showed initial stromal
      damage with collagen disorganization, mild stromal edema, and initial signs of
      keratocyte damage. Half of the corneas at 60 degrees C for 10 seconds were
      examined at time 0 and the other half after 1 week. At time 0, massive corneal
      damage with epithelial cell edema, collagen disorganization, severe stromal
      edema, intrastromal vacuole formation, plump keratocyte nuclei, and endothelial
      cell detachment were found, as was a severely impaired nerve plexus. At 1-week
      follow-up, corneas showed persistent stromal and endothelial cell edema with an
      increase activated keratocytes and mitotic features in the stroma and the
      epithelial layer. CONCLUSIONS: Rabbit corneas showed a considerable tolerance to
      US damage up to 50 degrees C. Higher thermal doses produced severe histological
      damage, even though corneas showed a considerable plasticity due to their
      regenerative capacity.

PMID- 16412937
TI  - Immunohistologic study of interleukin-1, transforming growth factor-beta, and
      alpha-smooth muscle actin in lens epithelial cells in diabetic eyes.
AB  - PURPOSE: To assess the effects of the cytokines interleukin-1 (IL-1),
      transforming growth factor-beta (TGF-beta), and alpha-smooth muscle actin (alpha
      SMA) in lens epithelial cells (LECs) in normal and diabetic eyes. SETTING:
      Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo,
      Japan. METHODS: Ten eyes of 10 patients with diabetic mellitus and 20 normal eyes
      of 20 patients with senile cataract were studied. The anterior lens capsules with
      LECs obtained by capsulotomy during cataract surgery were cultured. The LECs
      obtained immediately after surgery and on the third day of culture were
      immunohistologically studied to assess the activities of the cytokines. RESULTS:
      Interleukin-1 and TGF-beta staining showed a low level activity in some LECs in
      diabetic eyes but only a minimum level of activity in those in normal eyes.
      During culture, LECs in diabetic eyes became small and transformed into fusiform
      and fibroblast-like cells, and these cells were strongly stained for IL-1 and TGF
      beta. Normal eyes showed little changes in cell morphology and were weakly
      stained for IL-1 and TGF-beta. Both with culture and with no culture, alpha-SMA
      showed only minimal activity in both diabetic and normal eyes, with no
      difference. CONCLUSION: Lens epithelial cells after cataract surgery had low IL-1
      and TGF-beta activities, and these activities increased during culture. Diabetic
      eyes showed higher cytokine activities and more marked morphologic changes than
      normal eyes, suggesting that increased proliferative activity and increased
      cytokine activity of LECs contribute to strong anterior capsule contraction in
      diabetic eyes.

PMID- 16412938
TI  - Late in-the-bag intraocular lens dislocation: incidence, prevention, and
      management.
AB  - Dislocation of an intraocular lens (IOL) with the capsular bag is a late
      complication of cataract surgery, reported with increasing frequency in recent
      years. Pseudoexfoliation, uveitis, myopia, and other diseases associated with
      progressive zonular weakening and capsular contraction are the predisposing
      conditions. Capsular tension rings probably help but do not prevent this
      complication. Management includes IOL exchange, replacement with an anterior or a
      sutured posterior chamber IOL, or suturing the IOL through the bag to the iris or
      the sclera.

PMID- 16412939
TI  - Ophthalmology and vision science research: part 2: How to commence research-
      Eureka or that's a little unusual?
AB  - Understanding the key elements that increase the likelihood of project success is
      fundamental for those embarking on research. The first article in this series
      placed scientific journals in perspective in relation to Journal Impact Factors
      and citation indices. This second article in a series primarily aimed at those
      commencing research, particularly in the area of ophthalmology and vision
      science, delineates the interrelated components that are required to complete a
      research project. Successful research projects seldom emerge from serendipitous
      observation, and most evolve through a combination of inspiration, careful
      planning, and a great deal of industry. Beginning researchers must first be clear
      about their reason(s) for pursuing research and should identify potential mentors
      and collaborators at the outset. This article discusses methods of identifying
      suitable projects and mentors. Ten component areas necessary to complete a
      research project are addressed, with reference to relevant published literature,
      under the following topic areas: mentors and collaborators; finding a research
      topic; confirming suitability of the topic; defining the research question;
      developing the hypothesis; key considerations in study design; threats to study
      validity; study sample size; benefits and limitations of clinical science;
      completing to publication. This guide is intended to be applicable to all
      embarking on research, but particularly to those with an interest in the visual
      system. The final 3 articles in this series will deal with writing a research
      paper to publication standard, working successfully with the journal review
      process, and refining electronic literature searches.

PMID- 16412940
TI  - Corneal edema and penetrating keratoplasty after anterior chamber phakic
      intraocular lens implantation.
AB  - Phakic intraocular lens (IOL) implantation is an increasingly popular option in
      surgical correction of refractive error. To date, reports of long-term morbidity
      are infrequent in the literature. We encountered 3 patients who experienced
      corneal decompensation and cataract progression following angle-fixated anterior
      chamber phakic IOL placement.

PMID- 16412941
TI  - Iris repair after a catastrophic laser in situ keratomileusis complication.
AB  - This report illustrates the surgical approach to and results of a complex iris
      reconstruction. The presentation and long-term visual and architectural results
      (follow-up of 4 years) of the repair of a severe anterior segment injury after
      entry into the anterior chamber by a microkeratome during laser in situ
      keratomileusis is described. The techniques used in the repair are described in
      detail, and a historical review of iris repair techniques is presented.

PMID- 16412942
TI  - Orbital inflammation after sub-Tenon's anesthesia.
AB  - Two cases of orbital swelling after sub-Tenon's anesthesia are reported. The
      first patient presented 3 days postoperatively with proptosis and conjunctival
      chemosis. Computed tomography showed nonspecific inflammation of the orbital soft
      tissue. Signs and symptoms resolved after systemic steroids. The second patient
      presented with similar signs and mild pain on the fourth postoperative day.
      Computed tomography showed a similar diffuse orbital inflammation. The patient
      was treated with oral steroids and antibiotics, and all inflammation subsided
      within 4 weeks. Both patients had uneventful cataract surgery, were apyrexial,
      and were generally well. A few possible mechanisms for these episodes are
      infection, reaction to povidone-iodine or sub-Tenon's anesthetic, or trauma due
      to the sub-Tenon's cannula.

PMID- 16412943
TI  - Cyanoacrylate repair of laser in situ keratomileusis corneal flap perforation by
      a snake bite.
AB  - A 30-year-old man who had laser in situ keratomileusis (LASIK) for myopia 1 year
      earlier developed a corneal perforation in the left eye from a boa constrictor.
      The patient presented to the emergency room, and a small corneal perforation just
      outside the visual axis was diagnosed within the LASIK flap. Cyanoacrylate
      adhesive was used to close the corneal perforation. The patient went on to full
      visual recovery with an uncorrected visual acuity of 20/20. This is the first
      reported case of a penetrating corneal injury from a serpent in an eye that had
      LASIK. Cyanoacrylate may be used to repair small traumatic corneal perforations
      with a favorable visual outcome in eyes that have had LASIK.

PMID- 16412944
TI  - Anterior chamber gas bubbles after corneal flap creation with a femtosecond
      laser.
AB  - A 48-year-old woman had bilateral wavefront-guided laser in situ keratomileusis
      for myopia with IntraLase corneal flap creation. In the right eye the cavitation
      bubbles were observed not only in the interface between the flap and the corneal
      bed but also in the anterior chamber disappearing after 30 minutes. After the
      procedure, uncorrected visual acuity is 20/25 in both eyes; and specular
      microscopy shows normal hexagonal cells and density. Although no postoperative
      complications were observed in our case, further follow-up is needed to examine
      the long-term effect of this phenomenon of IntraLase.

PMID- 16412945
TI  - Intracameral cefazolin to prevent endophthalmitis in cataract surgery: 3-year
      retrospective study.

PMID- 16412946
TI  - Intraocular pressure after phakic posterior chamber intraocular lens
      implantation: 5-year follow-up.

PMID- 16412947
TI  - Digital camera for still and video intraoperative photography in ophthalmology.

PMID- 16412948
TI  - Artificial tears for clearing tear-film precipitation during cataract surgery.

PMID- 16412949
TI  - Prospective evaluation of a pragmatic treatment rationale: open reduction and
      internal fixation of displaced and dislocated condyle and condylar head fractures
      and closed reduction of non-displaced, non-dislocated fractures Part II: high
      condylar and condylar head fractures.
AB  - This study prospectively evaluated closed reduction (CR) outcomes in non
      displaced, non-dislocated high-condylar and condylar-head fractures (Class VI
      after Spiessl and Schroll) and open reduction and internal fixation (ORIF) of
      displaced (Class III) or dislocated (Class V) fractures. Thirty-eight patients
      with 54 fractures (16 (42%) with bilateral fractures, 14 (37%) CR, 24 (63%) ORIF)
      were enrolled in a 1 year follow-up that 18 patients with 33 fractures completed.
      Condylar translation in Class VI fractures recovered to 11 mm for vertical
      opening, 8mm for protrusion and 10 mm for mediotrusion; Class III synonymously 8
      mm, 8 mm and 6 mm; and Class V 7 mm, 6mm and 7 mm; incisal movements recovered to
      38 mm, 8 mm and 8 mm in Class VI; 55 mm, 7 mm and 10 mm in Class III with 1 (8%)
      malocclusion, 1 (8%) impaired vertical opening and 55 mm, 7 mm and 9 mm in Class
      V with 2 (18%) malocclusions. Fragment-reduction versus the non-fractured condyle
      was -0.3 mm to +1.3 mm and +3 degrees to +9 degrees in Class VI, -1 mm to -0.2 mm
      and +3 degrees to +2 degrees in Class III, -3.3 mm to +3.1 mm and -11.2 degrees
      to +1 degrees in Class V. Malocclusion and joint locking were unreliable
      determinants for a treatment decision, being forged by concomitant fractures.
      Joint movements were within normal range at 1-year follow-up except Classes III
      and V vertical opening translation. After predefined criteria, 92% successful
      outcomes were attained. Multiple factor analysis should be used to prospectively
      evaluate the unacceptable clinical outcomes. Class VI fractures with intact
      vertical support should prospectively be evaluated whether these benefit from
      ORIF.

PMID- 16412950
TI  - Towards a computer-aided diagnosis system for vocal cord diseases.
AB  - OBJECTIVE: The objective of this work is to investigate a possibility of creating
      a computer-aided decision support system for an automated analysis of vocal cord
      images aiming to categorize diseases of vocal cords. METHODOLOGY: The problem is
      treated as a pattern recognition task. To obtain a concise and informative
      representation of a vocal cord image, colour, texture, and geometrical features
      are used. The representation is further analyzed by a pattern classifier
      categorizing the image into healthy, diffuse, and nodular classes. RESULTS: The
      approach developed was tested on 785 vocal cord images collected at the
      Department of Otolaryngology, Kaunas University of Medicine, Lithuania. A correct
      classification rate of over 87% was obtained when categorizing a set of unseen
      images into the aforementioned three classes. CONCLUSION: Bearing in mind the
      high similarity of the decision classes, the results obtained are rather
      encouraging and the developed tools could be very helpful for assuring objective
      analysis of the images of laryngeal diseases.

PMID- 16412951
TI  - Evidence for physical therapies (airway clearance and physical training) in
      cystic fibrosis: an overview of five Cochrane systematic reviews.
AB  - BACKGROUND: A range of physical therapies (including airway clearance and
      physical training) are used in cystic fibrosis (CF). The aim of this paper is to
      summarise the main findings from Cochrane systematic reviews that have considered
      the evidence for physical therapies in CF. METHODS: All outcomes reported in
      relevant Cochrane systematic reviews are summarised. RESULTS: Review 1 provides
      some evidence from short-term trials of the benefit of airway clearance over no
      airway clearance in improved mucus transport but no definitive evidence from long
      term trials to support the efficacy of airway clearance over no airway clearance;
      review 2 provides some evidence that conventional chest physiotherapy (CCPT) is
      at least as effective as other forms of airway clearance, but that patients may
      have a preference for self-administered treatments over CCPT; review 3 provides
      some evidence that positive expiratory pressure (PEP) is at least as effective as
      other forms of airway clearance; review 4 provides some evidence to support the
      use of non-invasive ventilation during airway clearance in patients with moderate
      to severe disease who have difficulty clearing sputum; review 5 provides some
      evidence of the benefits of different types of physical training. CONCLUSION: The
      Cochrane systematic reviews summarised in this paper provide some evidence to
      support the inclusion of physical therapies in the care-management plan of CF.
      They also provide information to steer the direction and focus of future research
      in this area.

PMID- 16412952
TI  - Presentation of the special issue on stem cells in transplantation medicine.

PMID- 16412953
TI  - Stem cells, tissue engineering and organogenesis in transplantation.
AB  - Tissue engineering is an attempt to generate living tissues for surgical
      transplantation. In vitro and in vivo approaches have led to the production of
      vascular and cardiovascular components, bones, cartilages and gastrointestinal
      tissues. Organogenesis has a different aim, which is to create transplantable
      organs from embryonic tissue implanted into the recipient's omentum. This
      approach has been successful in creating kidneys and pancreases in animals. The
      use of stem cells in organogenesis and in tissue engineering has vastly enlarged
      the potential for clinical applications. The technique of nuclear transfer offers
      the possibility of creating cells, which are genetically identical to the host.
      Tissue engineering and organogenesis represent the future of transplantation in
      medicine. The progress in this field is of tremendous importance because it can
      produce a new generation of morphologically complex tissues and organs. In this
      review, the most relevant experiences in this area are summarized, including its
      perspectives for therapeutical applications.

PMID- 16412954
TI  - Stem cell transplantation for the treatment of myocardial infarction.
AB  - Stem cell transplantation provides a potential regenerative therapy for the heart
      damaged by myocardial infarction. Numerous scientific studies have been
      undertaken in animals and humans to analyze the safety and efficacy of this new
      approach. However, at the present time, the results have been mixed and
      inconclusive, and the mechanism of stem cell transplantation therapy remains
      unclear. This review discusses the controversies and problems that need to be
      addressed in future investigations.

PMID- 16412955
TI  - Stem cells for the treatment of liver disease.
AB  - Stem cells tantalise. They alone have the capacity to divide exponentially,
      recreate the stem cell compartment as well as create differentiated cells to
      build tissues. They should be the natural candidates to provide a renewable
      source of cells for transplantation. Does the reality support the promise of this
      exciting alternative to conventional therapies for metabolic and degenerative
      liver disease? Can techniques be developed to provide the large number of cells
      that could be required? Must there be "space" in the liver to accept the cells?
      To what extent is the liver immunoprivileged, and is immunosuppression necessary
      for stem cell therapy? Is it better to use haematopoietic stem cells, fetal stem
      cells, mesenchymal cells, embryonic stem cells, hepatocytes or all of the above,
      but for different disease indications? This paper discusses why the exploration
      of stem cells for the treatment of liver disease is of great potential, and
      delineates some of the hurdles that need to be overcome before patients see
      benefits from laboratory-based research into stem cell transplantation and
      function.

PMID- 16412956
TI  - Insulin-secreting cells derived from stem cells: clinical perspectives, hypes and
      hopes.
AB  - Diabetes is a degenerative disease that results from the selective destruction of
      pancreatic beta-cells. These cells are responsible for insulin production and
      secretion in response to increases in circulating concentrations of nutrients,
      such as glucose, fatty acids and amino acids. This degenerative disease can be
      treated by the transplantation of differentiated islets obtained from cadaveric
      donors, according to a new surgical intervention developed as Edmonton protocol.
      Compared to the classical double transplant kidney-pancreas, this new protocol
      presents several advantages, concerning to the nature of the implant,
      immunosuppressive drug regime and the surgical procedure itself. However, the
      main problem to face in any islet transplantation program is the scarcity of
      donor pancreases and the low yield of islets isolated (very often around 50%)
      from each pancreas. Nevertheless, transplanted patients presented no adverse
      effects and no progression of diabetic complications. In the search of new cell
      sources for replacement trials, stem cells from embryonic and adult origins
      represent a key alternative. In order to become a realistic clinical issue
      transplantation of insulin-producing cells derived from stem cells, it needs to
      overcome multiple experimental obstacles. The first one is to develop a protocol
      that may allow obtaining a pure population of functional insulin-secreting cells
      as close as possible to the pancreatic beta-cell. The second problem should
      concern to the transplantation itself, considering issues related to immune
      rejection, tumour formation, site for implant, implant survival, and biosafety
      mechanisms. Although transplantation of bioengineered cells is still far in time,
      experience accumulated in islet transplantation protocols and in experiments with
      appropriate animal models will give more likely the clues to address this
      question in the future.

PMID- 16412957
TI  - Human embryonic stem cell-derived oligodendrocyte progenitors for the treatment
      of spinal cord injury.
AB  - Stem cells are self-renewing, pluripotent cells that can be manipulated in vitro
      to differentiate into virtually any cell type. Stem cells are highly
      proliferative and have the potential to expand into very large numbers of a
      desired cell lineage. As such, they represent an excellent source of cells for
      cellular replacement strategies in disease states that are typified by a loss of
      a particular cell population. Recent studies have indicated that spinal cord
      injury is accompanied by chronic progressive demyelination, and have thus
      identified oligodendrocytes as a desirable transplant population for
      remyelination strategies. To address this need, we developed a method to
      differentiate hESCs into high purity human oligodendrocyte progenitor cells
      (OPCs). Transplantation into spinal cord injury sites in adult rats resulted in
      remyelination and functional repair. Here, we summarize these findings and
      present new data concerning the effects of hESC-derived OPC transplantation on
      the host environment.

PMID- 16412958
TI  - Stem cell transplantation as a therapeutic strategy for traumatic brain injury.
AB  - Stem cell transplantation has enormous potential to be a viable therapeutic
      approach to replace the lost tissue/cells following traumatic brain injury (TBI).
      Several types of cell lines such as immortalized progenitors cells, embryonic
      rodent and human stem cells and bone marrow-derived cells have been successfully
      transplanted in experimental models of TBI, resulting in reduced neurobehavioral
      deficits and attenuation of histological damage. To date, it remains unclear
      whether stem cell are effective following transplantation into the injured brain
      via either cell replacement, trophic support, or manipulation of the local
      environment to stimulate endogenous neuroprotection/regeneration. This paper will
      review the most current and exciting pre-clinical data regarding the utility of
      cellular transplantation in experimental models of TBI. We believe that further
      work must continue to better understand the interaction between the host and the
      transplanted cells as well as the mechanisms regulating their differentiation
      into mature and functionally active neurons/glia.

PMID- 16412959
TI  - Challenges in therapeutic strategies for transplantation: where now from here?
AB  - The current standard of care in transplantation reliably achieves acceptable
      graft and patient survival but still depends on life long immunosuppression in
      most patients. Current strategies employ medications that, in general, inhibit
      distal events mediating rejection, namely T cell activation and cytotoxicity.
      They do not typically interfere with initial allorecognition or the factors that
      influence the direction of an immune response (towards cytotoxicity as opposed to
      anergy or regulation). Given the exponential amplification of immune responses,
      these proximal targets may be more efficient in preventing rejection. Recent
      laboratory investigations have identified several approaches, e.g., costimulation
      blockade, depletion, and hematopoietic chimerism, that influence the initial
      stages of the alloimmune response, or establish self-perpetuating means of
      eliminating rejection without chronic immunosuppression. This manuscript reviews
      methods of immune manipulation that the authors view as promising for future
      exploitation and transfer to the clinic. These therapies are similar in that they
      are viewed as attempts to influence the ability of the body to mount an immune
      response and its subsequent direction, as opposed to supplying late effector
      phase inhibition. While it is recognized as unlikely that any one therapy will
      universally lead to tolerance, the authors propose that these concepts will make
      immunosuppressive drug minimization more readily successful.

PMID- 16412960
TI  - Engraftment of human T, B and NK cells in CB.17 SCID/beige mice by transfer of
      human spleen cells.
AB  - Models of severe combined immuno-deficient (SCID) mice reconstituted with a
      competent human immune system represent a valuable tool for the study of human
      immune responses in vivo. Reconstitution with human cells can be achieved using
      large numbers of peripheral blood lymphocytes, but levels of engraftment are poor
      and graft versus host disease (GVHD) frequently occurs. SCID/beige mice are at
      the same time deficient for adaptive and innate immunity and the objective of
      this study was to develop a safe and efficient way to achieve human lymphocyte
      engraftment in these mice using human spleen cells. After institutional
      authorisations and informed consent of relatives, a piece of spleen was obtained
      from cadaveric organ donors and the splenocytes were isolated and cryopreserved
      for later use. Single intraperitoneal injections of 5-100 x10(6) splenocytes were
      performed into SCID/beige mice. Reconstitution of a human immune system was
      monitored weekly by the presence of human cells and IgG in peripheral blood. The
      mice were sacrificed 4 weeks after the injection and the engraftment in lymphoid
      organs was studied. A reproducible reconstitution was obtained with
      intraperitoneal injection of 30-40 x10(6) spleen cells. Human T, B and NK cells
      as well as human IgG were present in peripheral blood. In lymphoid tissues, the
      same lymphocytic subpopulations were detected and in addition some antigen
      presenting cells. The reconstitution was functional because graft rejection was
      observed after transplantation of human allogeneic tissues. When less than 30
      x10(6) cells were injected, the reconstitution was variable. When more than 40
      x10(6) cells were injected, GVHD occurred with increasing frequency. In
      conclusion, we show that intraperitoneal injection of 30-40 x10(6) human
      splenocytes into SCID/beige mice induces a quick and functional engraftment of
      human T, B and NK cells with no risk of GVHD. This model may be used to study
      human transplantation immunobiology in vivo.

PMID- 16412961
TI  - Differential expression of tissue factor (TF) in calcineurin inhibitor-induced
      nephrotoxicity and rejection--implications for development of a possible
      diagnostic marker.
AB  - Deposition of fibrin in the form of fibrinoid necrosis is a common feature of
      severe acute renal allograft rejection. The role of the coagulation system and
      its initiator tissue factor (TF) during this process is, however, still poorly
      understood. In this study, we analyzed the expression of TF in 88 renal
      transplants afflicted with different forms of rejection and calcineurin inhibitor
      induced nephrotoxicity, to see whether there was differential expression of this
      protein. TF immunoreactivity was evaluated semiquantitatively in six different
      renal structures: the podocytes, Bowman epithelium, the endothelium of the
      glomeruli, the brush border of tubular cells, the thin ascending loop of Henle,
      and small arteries/arterioles. The TF expression of normal renal tissue (n=6) was
      restricted to the glomerular podocytes and Bowman epithelium, and to some extent
      the ascending loop of Henle. Renal allografts undergoing acute rejection (AR) of
      grades I-III, (n=13, n=17 and n=12, respectively) did not show any altered TF
      expression in the glomeruli or vascular endothelium. In the ascending loop of
      Henle, a reduced expression could be seen (ARI, p=0.015; and ARII, p=0.043). TF
      staining of the brush border of renal transplants undergoing acute cyclosporin A
      (CsA) nephrotoxicity (n=18) was significantly higher than in normal kidneys
      (p=0.0003), as well as in transplants undergoing various degrees of acute
      rejection (ARI, p=0.027; ARII, p=0.0012; and ARIII, p=0.0001). Tubular brush
      border-expressed TF was also evident in 10 of 15 allografts suffering from
      chronic CsA nephrotoxicity, compared to 4 out of 13 cases with chronic allograft
      vasculopathy (CAV), but the increase was not statistically significant relative
      to normal kidneys. The majority of the grafts afflicted with either of the two
      chronic conditions displayed a TF-positive arterial endothelium (CAV, p=0.0034;
      and chronic CsA nephrotoxicity, p=0.0026) relative to controls. In conclusion,
      these results indicate that vascular TF expression is not altered during acute
      rejection, but may be of importance in chronic allograft nephropathy.
      Furthermore, TF immunoreactivity in the tubular brush border may be specific to
      acute CsA nephrotoxicity and might be used as a biomarker for this condition.
      Further studies are required to evaluate the possible role of brush border
      expressed TF in the pathogenesis of CsA nephrotoxicity.

PMID- 16412962
TI  - Chimerism does not influence graft-versus-myeloma and graft-versus-host disease
      in reduced intensity setting.
AB  - In this study we serially evaluated the chimerism status in 20 multiple myeloma
      patients allotransplanted with a reduced intensity regimen. All patients
      engrafted, with total 75% overall responses and 35% of CRs. After a median follow
      up of 35 months, seven patients (35%) died, three of them due to disease
      progression. Four patients died before day +100, with a TRM of 20%. Nine patients
      (45%) developed aGVHD and six (40%) had cGVHD. Twenty-five percent of patients
      achieved full donor chimerism (FDC) before day +100, 42% before day +200 and 75%
      24 months after graft. In our series, level of chimerism did not correlate with
      either the quality of response or aGVHD. No significant differences were found
      between bone marrow and peripheral blood samples. Analogously, even if donor DNA
      percentage often resulted higher in the PMN fraction than in the mononuclear one,
      these differences were not significant after statistical analysis. On the other
      hand, cGVHD was associated with increased rates of FDC, with 6/6 cases showing a
      full donor pattern in concomitance of the cGVHD versus 5/9 cases presenting a FDC
      in the group of patients without cGVHD (p=0.057). The Kaplan-Meier estimates of
      OS and PFS at 2 years were 59% and 58%, respectively; chimerism pattern did not
      impact in the predicting clinical outcome. In summary, our study shows that a
      stable engraftment and high frequency of donor chimerism are achievable after a
      reduced intensity conditioning regimen. Moreover, even as result of a single
      center experience, we suggest that chimerism, graft-versus-myeloma and GVHD would
      represent distinct entities that require larger immunological studies for further
      clarification.

PMID- 16412964
TI  - Kidney transplantation: success breeds failure.

PMID- 16412965
TI  - Anemia in the kidney-transplant patient.
AB  - Anemia, a potentially correctable cardiovascular risk factor, continues to be a
      major problem in kidney-transplant patients. Erythropoietin levels increase
      rapidly after successful kidney transplantation, and by 3 months, most patients
      achieve hemoglobin levels greater than 12 g/dL. Anemia may be caused by problems
      commonly seen in the general population such as iron deficiency or
      gastrointestinal blood loss, by immunosuppressive medications, or by more rare
      abnormalities such as hemolytic uremic syndrome or parvovirus B19-induced
      aplastic anemia. Iron deficiency is common at the time of transplantation and
      beyond and frequently contributes to anemia. Markers of iron deficiency (ferritin
      or transferrin saturation) are frequently inconclusive because of the presence of
      inflammation and infection. Immunosuppressive medications, such as azathioprine
      and mycophenolate mofetil (MMF), are a common cause of mild bone-marrow
      suppression and, thus, anemia. Sirolimus can cause more severe bone-marrow
      suppression, although this effect can lessen over time. The transplant patient
      with chronic kidney disease (CKD) frequently develops anemia, yet agents such as
      epoetin-alpha and darbepoetin are greatly underutilized. Evaluation of anemia
      should be undertaken when hemoglobin fails to normalize by 3 months after
      transplantation. Later after transplantation, especially in the setting of
      chronic allograft dysfunction, evaluation should take place when the hemoglobin
      falls to less than 11 g/dL in premenopausal females or to less than 12 g/dL in
      males and postmenopausal females.

PMID- 16412967
TI  - Considerations in retransplantation of the failed renal allograft recipient.
AB  - Routine success in kidney transplantation has significantly improved the quality
      and length of life for the majority of recipients and made this option the
      treatment of choice for suitable candidates. Improved patient survival combined
      with a relative static improvement in long-term graft outcomes has led to an
      increasing number of transplant recipients with failed allografts who face the
      eventual option of either returning to dialysis or seeking retransplantation.
      Although retransplantation is presumed to be a favorable option for many, data to
      support this belief is limited. Given the wide variance in predicted outcomes for
      retransplantation, on the basis of the underlying kidney disease and other
      individual patient comorbidities as well as the expected wait time for a second
      transplant, each case should be evaluated independently. This review discusses
      available data and individual considerations that should be taken into account
      when retransplantation is proposed after failure of a primary allograft.

PMID- 16412966
TI  - Long-term trends in allograft survival.
AB  - Kidney transplantation has changed dramatically over the past decade. Many
      advances have occurred that result in shorter hospital stays, decreased acute
      rejection, less infectious morbidity, and improved long-term allograft survival.
      Many factors are responsible for the improvement in kidney transplantation, and
      these factors are discussed in this review. These successes have led to a paradox
      in the care of the kidney-transplant recipient, however. As the short-term
      complications are prevented or successfully managed, more patients will develop
      chronic problems with the function of the allograft.

PMID- 16412968
TI  - Chronic kidney disease in solid-organ transplantation.
AB  - As the long-term survival of nonrenal solid-organ transplant recipients continues
      to improve, more complications related to transplantation occur. Among the most
      serious is chronic kidney disease (CKD). Although CKD was previously thought to
      only clinically affect a minority of this population, closer measurements of
      kidney function and monitoring of CKD complications now show that CKD will affect
      a significant number, if not a majority, of transplant recipients-particularly
      the long-term survivors who often have excellent function of their primary
      allograft. This article will review the incidence, risk factors, treatment, and
      outcomes of patients who develop CKD after heart, liver, and lung
      transplantation.

PMID- 16412969
TI  - Bone disease after kidney transplantation.
AB  - Advances in immunosuppressive therapy have allowed for enhanced allograft
      survival in kidney transplantation. With this increasing success of
      transplantation, however, has come a greater appreciation of subsequent
      complications, such as bone and mineral disease. In patients with chronic kidney
      disease who are awaiting transplantation, disorders in mineral metabolism and
      renal osteodystrophy are an essentially universal finding, and several different
      pathophysiologic mechanisms are believed to contribute to the development of
      these disorders.

PMID- 16412970
TI  - Calcineurin nephrotoxicity.
AB  - Calcineurin inhibitors, cyclosporine and tacrolimus, have improved allograft
      survival in solid organ transplantation. Indeed, they have reduced the incidence
      of acute rejection episodes of cadaveric allograft recipients. Although marked
      progression has been made in initial survival rates, long-term kidney graft
      survival has yet to show such encouraging results. Chronic allograft dysfunction
      is the major hindrance to long-term graft survival and many components contribute
      to this entity, both immunologic and nonimmunologic. Chronic calcineurin
      nephrotoxicity is a major factor in chronic allograft dysfunction. This review
      will highlight the current understanding and management of calcineurin
      nephrotoxicity in kidney transplantation.

PMID- 16412971
TI  - Chronic allograft nephropathy.
AB  - With the advent of calcineurin inhibitors, the success of kidney and other solid
      organ transplants has improved significantly from the standpoint of reducing the
      incidence of acute rejection. Over the past 2 decades, both short-term allograft
      survival and acute rejection rates have dramatically improved with improved
      diagnostic and therapeutic techniques such as standardized pathology scoring;
      potent antirejection drugs such as anti-thymocyte globulin, interleukin-2
      receptor antibodies, cyclosporine, tacrolimus, sirolimus, and mycophenolate
      mofetil; and improved infection control such as valganciclovir and antifungal
      therapy. However, long-term graft loss has remained at nearly constant levels
      over the same period of time, with the average half-life of a deceased-donor
      kidney transplant in the United States remaining approximately 1 decade. In
      addition to death with a functioning allograft and calcineurin toxicity, a
      chronic fibrotic process-known at various times as chronic rejection, chronic
      allograft dysfunction, and chronic allograft nephropathy (CAN)-account for the
      leading causes of transplant failure.

PMID- 16412972
TI  - Special issues in pediatric kidney transplantation.
AB  - Pediatric and adult kidney transplantation differ in many ways, but one of the
      most significant differences is the impact of kidney disease and kidney
      transplantation on growth and development in pediatric patients. Multiple facets
      of transplantation may have an impact on growth and development, including the
      timing of transplantation, choice of immunosuppressive agents, and the presence
      of hypertension. In addition, graft function has a significant impact on linear
      growth, and so preservation of function becomes important not only for general
      health and quality of life but also for optimizing growth. Other concerns in
      pediatric kidney transplantation include a heightened risk for
      posttransplantation infectious complications, including lymphoproliferative
      disease. In addition, the impact of immunosuppressive drugs on adherence to
      therapy is important. Although adherence is a complex and multifactorial process,
      immunosuppressive drugs that cause physical side effects may contribute to drug
      nonadherence because children, and particularly adolescents, may be inclined to
      stop taking medications associated with physical changes that differentiate them
      from their peers. Studies that further delineate factors that affect growth and
      development, risk for infectious complications, and nonadherence will be
      important to maximize outcomes in pediatric kidney transplantation.

PMID- 16412973
TI  - Internet organ solicitation, explained.
AB  - The growth of internet-based communications and the increasing demand for living
      organ donors are resulting in more use of Web sites for organ solicitation. Web
      resources have the capacity to improve public awareness about both organ
      donations and transplant outcomes. Rules for organ donation and fair allocation
      must follow legal principles regarding organ solicitation. Categories of internet
      recipient/donor matching services include "clearing house," "membership," and
      "individual" sites. All these raise ethical concerns related to the individual
      recipient/donor relationship and to the current system of organ allocation.
      However, a lack of rules and regulations regarding internet solicitation exists.
      Several pragmatic steps are proposed.

PMID- 16412974
TI  - Impact of locus of control on clinical outcomes in renal dialysis.
AB  - This study focused on the relationship between patients' locus of control and
      their ability to improve selected clinical outcomes related to kidney dialysis.
      The main hypothesis of this study stated that patients who viewed themselves as
      having control over their situation would be more successful at improving
      targeted clinical outcomes than those who believed someone other than themselves
      had control over their situation. The study found that interventions aimed at
      increasing awareness of who has control and reducing the aspect of chance had a
      more significant positive impact on outcomes than did pure cognitive or
      educational interventions geared mainly toward emotional issues or educational
      deficits. Interventions that work with the dominant locus of control to increase
      awareness of where control lies appeared to be more effective in assisting the
      patients to improve their targeted clinical outcomes rather than are
      interventions to change the locus of control between internal and powerful others
      (external).

PMID- 16412975
TI  - Outcomes study of a customer relations educational program in dialysis practice.
AB  - In the fall of 2003, a customer relations staff educational program was
      instituted for use throughout Renal Care Group. After 1 year and 4 months, an
      outcomes study was implemented to evaluate and revise the program. The program is
      taught by the dialysis social worker to the rest of the dialysis health-care team
      to increase customer relations skills with the patients, their families, and
      dialysis coworkers. Today, more than ever, patients are seeking better quality
      health care not only in technical skills but also in compassionate care. Pretest
      and posttest scores from each training session indicated the necessity of this
      training and knowledge gained. Through a survey of instructors, strengths of the
      program were identified, as well as were areas that needed revision. In addition
      to providing helpful information, some of the main strengths of the program
      indicated by instructors were team building and problem solving. Revisions
      consisted primarily of shortening the modules and simplifying the program's use.

PMID- 16412976
TI  - Oral lesions of 500 habitual psychoactive substance users in Chennai, India.
AB  - The aim of this study was to ascertain the prevalence of oral lesions among 500
      psychoactive substance users in a hospital-based population. The study group
      consisted of 500 consecutive patients attending TTK Hospital, a non-governmental
      organisation involved in rehabilitation of substance users. Patient history was
      recorded in a pre-determined format and clinical findings were recorded by a
      trained physician and dental surgeons. Psychoactive substances used by the
      patients were alcohol (97%), tobacco (72%), arecanut (57.2%), narcotics (6.8%),
      cannabis (3.2%) and benzodiazipines (1.8%). Ninety-one percent of patients had
      one or more oral lesions: dental caries (39%), gingivitis (37.6%), extrinsic
      stains (24%), oral submucous fibrosis (OSF) (8%), periodontitis (7.4%),
      leukoplakia (6.6%), melanosis (5.2%), nicotina palatini (2.2%) and erythroplakia
      (0.6%). For OSF, those using arecanut and alcohol had an odds ratio (OR) of 2.4
      [95% confidence intervals (CI) 1.23-4.69, P=0.009], smokers using arecanut
      products and alcohol had an OR of 3.07 (95% CI 1.59-5.91, P=0.000), and smokers
      who chewed arecanut products and used drugs had an OR of 23.1 (95% CI 2.05-260,
      P=0.001) compared with the general population. Those who smoked and used alcohol,
      arecanut and drugs had a 20.67-fold higher risk of developing leukoplakia
      compared with those who did not engage in these habits. In conclusion, 91% of
      patients had one or more oral lesions that needed dental treatment, and most
      patients were not aware of their oral lesions. The high prevalence of OSF and
      leukoplakia in substance abusers compared with the general population emphasises
      the need for regular dental assessments in these patients.

PMID- 16412977
TI  - Distinctions between separation anxiety and social anxiety in children and
      adolescents.
AB  - Separation anxiety and social phobia are intertwined to a considerable degree,
      and high comorbidity rates have been reported. The present study used latent
      class analysis (LCA) to investigate if classes of children and adolescents with
      simultaneously-high rates of separation anxiety and low rates of social anxiety
      symptoms, or vice versa, could be identified. Eight- to 18-year-olds from a large
      general population (n=1000) and referred sample (n=735) were assessed with the
      Multidimensional Anxiety Scale for Children (MASC). With LCA, a separate class of
      referred 8-11-year-old children with high separation anxiety scores, and
      simultaneously lower social anxiety scores was identified, next to a class of
      children with high scores on separation anxiety and social anxiety. In the other
      groups (referred 12-18-year-olds and children and adolescents from the general
      population), a class with individuals who specifically scored high on separation
      anxiety could not be revealed. The results indicated that separation anxiety
      represents a different construct than social anxiety in referred children (but
      not in referred adolescents or in the general population). It can be concluded
      that, in referred children, research regarding etiology and treatment outcome of
      anxiety symptoms should be aimed specifically at separation anxiety and social
      anxiety, instead of just investigating a broader anxiety dimension.

PMID- 16412978
TI  - Monoubiquitination of the nonhomologous end joining protein XRCC4.
AB  - Nonhomologous end joining is one of the major pathways by which cells repair
      double-strand breaks, and the XRCC4-DNA ligase IV complex is required for the
      ligation step. To better understand the regulation and stability of XRCC4 and DNA
      ligase IV, we investigated the ubiquitination status of these two proteins. We
      identified a predominantly monoubiquitinated form of XRCC4, and higher molecular
      weight forms of ubiquitinated XRCC4 were detected in lower abundance. In response
      to etoposide-induced DNA damage, ubiquitinated XRCC4 became more pronounced and
      was additionally phosphorylated. We confirmed that DNA ligase IV is unstable in
      the absence of XRCC4, with a half-life of approximately 30-90 min. Unlike XRCC4,
      we did not detect ubiquitinated forms of DNA ligase IV, and we found that the
      presence of XRCC4 stabilized DNA ligase IV more significantly than proteasome
      inhibitors. Monoubiquitination of XRCC4 may play a critical role in the
      regulation of nonhomologous end joining.

PMID- 16412979
TI  - Screening for genes preferentially expressed in the early phase of
      chondrogenesis.
AB  - This study reports a new system that is very effective in identifying genes
      closely related to the early phase of chondrogenic differentiation. While
      studying chondrogenesis in a progenitor cell line, ATDC5, we found that the
      amount of culture media overlying an ATDC5 monolayer affected the extent to which
      differentiation occurred. Therefore, to gain insight into the molecular
      mechanisms of chondrogenic differentiation, differential gene expression between
      differentiating and non-differentiating ATDC5 cultures was examined by
      suppression subtractive hybridization analysis. In this study, we focused on
      transcription factors that were identified in differentiating cultures, and found
      that activating transcription factor 5, ATF5, exhibited a conspicuous activation
      pattern using two methods to induce chondrogenesis of ATDC5 cells. Furthermore,
      ATF5 was found to be elevated in the developing limb bud by in situ hybridization
      in a pattern that was highly restricted to the cartilaginous anlagen, suggesting
      a positive association with ATF5 expression and chondrogenesis.

PMID- 16412980
TI  - A novel iron responsive element in the 3'UTR of human MRCKalpha.
AB  - Human untranslated region (UTR) databases were searched to identify novel
      proteins potentially regulated by an iron responsive element (IRE), and found two
      candidates-cell cycle phosphatase Cdc14A variant 1 and myotonic dystrophy kinase
      related Cdc42-binding kinase alpha (MRCKalpha), both possessing a putative IRE in
      their 3'UTR. In further experiments, we focused on MRCKalpha. Biochemical
      analyses of the MRCKalpha IRE revealed that it was functional and mediated the
      response to iron level in the same way as transferrin receptor 1 IREs (TfR) did.
      Similarly to TfR mRNA, MRCKalpha mRNA is stabilized, when iron supply is low,
      while it is destabilized under iron-rich conditions. The expression of MRCKalpha
      mRNA was found to be ubiquitous; the highest levels were noted in testes, the
      lowest in skeletal muscle. The level of MRCKalpha mRNA in various tissues
      strongly positively correlates with the level of TfR mRNA, indicating its
      possible role in the transferrin iron uptake pathway.

PMID- 16412981
TI  - A novel cell model to study the function of the adrenoleukodystrophy-related
      protein.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder due to
      mutations in the ABCD1 (ALD) gene. ALDRP, the closest homolog of ALDP, has been
      shown to have partial functional redundancy with ALDP and, when overexpressed,
      can compensate for the loss-of-function of ALDP. In order to characterize the
      function of ALDRP and to understand the phenomenon of gene redundancy, we have
      developed a novel system that allows the controlled expression of the ALDRP-EGFP
      fusion protein (normal or non-functional mutated ALDRP) using the Tet-On system
      in H4IIEC3 rat hepatoma cells. The generated stable cell lines express negligible
      levels of endogenous ALDRP and doxycycline dosage-dependent levels of normal or
      mutated ALDRP. Importantly, the ALDRP-EGFP protein is targeted correctly to
      peroxisome and is functional. The obtained cell lines will be an indispensable
      tool in our further studies aimed at the resolution of the function of ALDRP to
      characterize its potential substrates in a natural context.

PMID- 16412982
TI  - Telomere length of normal leukocytes is affected by a functional polymorphism of
      hTERT.
AB  - Transcriptional regulation of human telomerase reverse transcriptase (hTERT), a
      catalytic subunit of telomerase, is essential for telomerase activity associated
      with telomere length. In this study, we investigated the effects of a (-1327)T/C
      polymorphism within the hTERT promoter region on the hTERT promoter activity and
      leukocyte telomere length in normal individuals. The promoter activity in the (
      1327)T-sequence was significantly higher than that in the (-1327)C-sequence (p =
      0.0004). For leukocyte telomere length, the (-1327)T-allele carriers had
      significantly longer than the (-1327)T-allele non-carriers (p = 0.0007). Also,
      there was no age-related shortening in leukocyte telomere length in the (
      1327)T/T (p = 0.6633) and (-1327)T/C subjects (p = 0.1691), whereas there was
      clear age-related telomere shortening in the (-1327)C/C subjects (p = 0.0117).
      These findings suggest that the functional (-1327)T/C polymorphism of hTERT is
      associated with leukocyte telomere length in normal individuals.

PMID- 16412983
TI  - Suppression of survival in human SKBR3 breast carcinoma in response to metal
      chelator complexes is preferential for copper-dithiocarbamate.
AB  - Since diethyl dithiocarbamate (DEDTC) forms complexes with either zinc or copper,
      and 8-hydroxyquinoline (8-OHQ) also complexes with copper, we now compared the
      cytotoxic activity of Cu[DEDTC]2, Zn[DEDTC]2 and Cu[8-OHQ]2. This report shows
      that at nanomolar levels, only copper-[DEDTC]2, suppresses proliferation and
      clonogenicity of SKBR3 human breast carcinoma, concurrently with induction of
      apoptosis-associated PARP fragmentation. Susceptibility to these agents was
      paralleled by reactive oxygen generation (ROS) and greater expression of anti
      oxidant enzymes like MnSOD and catalase, with no comparable effect on Cu/Zn
      superoxide dismutase. The lethal effects of Cu[DEDTC]2 manifested when adding the
      two separate aqueous components or the preformed synthetic complexes in DMSO, was
      prevented by N-acetyl cysteine or glutathione, with no comparable protection
      afforded by non-thiol anti-oxidants like mannitol or DMSO. Exogenously added
      catalase also protected cells from Cu[DEDTC]2, suggesting that this complex may
      kill after the levels of superoxide anion [O2*-] dismutated by MnSOD increase
      hydrogen peroxide-related stress. Cu[DEDTC]2 also induced p21WAF1, a cdk
      inhibitor usually not inducible in mutant p53 tumors like SKBR3 carcinoma,
      correlating with dephosphorylation of the Sp1 transcription factor.
      Concentrations of Cu[DEDTC]2 cytotoxic for SKBR3 carcinoma did not induce
      comparable damage versus normal diploid human WI-38 fibroblasts. In contrast to
      the cytotoxic effect of nM levels of Cu[DEDTC]2 against SKBRR3 cells, no response
      was seen in the same cells exposed to 20 microM cis-platin. Since neither DEDTC
      bound to zinc, nor copper bound to 8-OHQ showed comparable cytotoxicity, our
      results suggest that the greater activity of copper-DEDTC reflects a specific
      structure-activity relationship for the active complex. Since Cu[DEDTC]2 shows
      more effectiveness than other metal-chelator complexes, it may be worth further
      investigation as an alternative to cancer therapies.

PMID- 16412984
TI  - Empirical antibacterial drug discovery--foundation in natural products.
AB  - Natural products have been a rich source in providing leads for the development
      of drugs for the treatment of bacterial infections. However, beyond the discovery
      of the natural product, thienamycin and the synthetic lead, oxazolidinone in the
      1970s, there has been a dearth of new compounds. This commentary provides an
      overview of current antibiotic leads and their mechanism of action, and
      highlights tools that can be applied to the discovery of new antibiotics.

PMID- 16412985
TI  - Glycopeptides: Update on an old successful antibiotic class.
AB  - The natural product glycopeptides vancomycin and teicoplanin have come to play a
      significant role in the therapy for Gram-positive bacterial infections. In
      particular vancomycin is the choice for empiric therapy of these infections
      primarily due to its activity against and the significance of methicillin
      resistant Staphylococcus aureus. While high-level problematic glycopeptide
      resistance among enterococci was observed initially and continues to increase,
      the slow creep of vancomycin intermediate susceptibility and the fear of frank
      resistance among the staphylococci have precipitated increasing work leading to
      creation of new semisynthetic analogs. These new agents, including dalbavancin
      and telavancin, are within 1-2 years availability in the clinic. Interestingly,
      chemical modifications resulting in these second-generation analogs and
      additional characterization have revealed new mechanisms of antibacterial action,
      and plasticity regarding additional properties including pharmacokinetics for the
      drug candidates. The unique beneficial properties of the near term vancomycin
      replacements, semisynthesis of additional important analogs, and advances in
      metabolic engineering resulting in novel scaffolds signal a new era for the
      glycopeptide antibiotics.

PMID- 16412986
TI  - Use of genomics to select antibacterial targets.
AB  - The problem of antibiotic resistance has eroded the usefulness of our arsenal of
      effective antibiotics. There is a need for new strategies to discover and develop
      new, effective drugs. The advent of the microbial genomics era has provided a
      wealth of information on a variety of microorganisms. This has allowed the
      identification and/or validation of a number of gene products that could serve as
      targets for the discovery of novel antibacterial agents. New genetic techniques
      and approaches have arisen in an attempt to exploit this newly available genomic
      data. Both random and targeted gene disruption efforts have proven effective in
      this process. Many of these methods would have been difficult to accomplish
      without DNA sequence and bioinformatics analyses. Several targets have been
      selected to further characterize and screen for inhibitors and one has yielded
      two clinical candidates.

PMID- 16412987
TI  - Family-based association test of the 5HTTLPR and aggressive behavior in a general
      population sample of children.
AB  - BACKGROUND: A promoter polymorphism in the serotonin transporter (5HTTLPR) has
      functional effects on an important physiologic process involved in serotonin
      (5HT) signaling. Despite the fact that variation in the 5HT system has long been
      implicated in the etiology of aggressive behaviors, only a few association-based
      studies with mixed results have been reported. METHODS: We conducted family-based
      tests of association in a sample of 366 families from which 1187 genotypes of the
      5HTTLPR were generated using polymerase chain reaction. Ratings of aggressive
      behavior were obtained from parents and teachers longitudinally using the Child
      Behavior Checklist (CBCL) and Teacher Report Form (TRF), instruments widely used
      in behavioral and psychiatric genetics. RESULTS: Within-family tests suggest an
      association between the s-allele of the 5HTTLPR and higher aggressive behavior in
      middle childhood. The strongest association was at age 9 and for an aggregate
      measure of teacher-rated aggressive behavior. CONCLUSIONS: This is the first
      report of an association analysis of the 5HTTLPR in a general population sample
      of school-age children. The results provide some support for the hypothesis that
      the functional effects of the 5HTTLPR s-allele are associated with higher levels
      of aggressive behavior in middle childhood.

PMID- 16412988
TI  - Brain mechanisms of fear extinction: historical perspectives on the contribution
      of prefrontal cortex.
AB  - What brain regions are involved in regulating behavior when the emotional
      consequence of a stimulus changes from harmful to harmless? One way to address
      this question is to study the neural mechanisms underlying extinction of
      Pavlovian fear conditioning, an important form of emotional regulation that has
      direct relevance to the treatment of human fear and anxiety disorders. In fear
      extinction, the capacity of a conditioned stimulus to elicit fear is gradually
      reduced by repeatedly presenting it in the absence of any aversive consequence.
      In recent years there has been a dramatic increase in research on the brain
      mechanisms of fear extinction. One region that has received considerable
      attention as a component of the brain's extinction circuitry is the medial
      prefrontal cortex (mPFC). In the present article, we review the historical
      foundations of the modern notion that the mPFC plays a critical role in emotional
      regulation, a literature that was largely responsible for studies that explored
      the role of the mPFC in fear extinction. We also consider the role of the mPFC in
      a broader neural circuit for extinction that includes the amygdala and
      hippocampus.

PMID- 16412989
TI  - Homocysteine-reducing strategies improve symptoms in chronic schizophrenic
      patients with hyperhomocysteinemia.
AB  - BACKGROUND: An elevated homocysteine level is reported to be a risk factor for
      several diseases, including Alzheimer's and cerebrovascular disease. Recently,
      several studies have reported that homocysteine levels are elevated in many
      schizophrenic patients. Homocysteine levels can be lowered by oral folic acid, B
      12, and pyridoxine. METHODS: Forty-two schizophrenic patients with plasma
      homocysteine levels >15 micromol/L were treated with these vitamins for 3 months
      and placebo for 3 months in a study with a randomized, double-blind, placebo
      controlled, crossover design. RESULTS: Homocysteine levels declined with vitamin
      therapy compared with placebo in all patients except for one noncompliant
      subject. Clinical symptoms of schizophrenia as measured by the Positive and
      Negative Syndrome Scale declined significantly with active treatment compared
      with placebo. Neuropsychological test results overall, and Wisconsin Card Sort
      (Categories Completed) test results in particular, were significantly better
      after vitamin treatment than after placebo. CONCLUSIONS: A subgroup of
      schizophrenic patients with hyperhomocysteinemia might benefit from the simple
      addition of B vitamins.

PMID- 16412991
TI  - The Lurcher mouse: fresh insights from an old mutant.
AB  - The Lurcher mouse was first discovered in 1954 as a spontaneously occurring
      autosomal dominant mutation that caused the degeneration of virtually all
      cerebellar Purkinje cells and most olivary neurons and granule cells. More recent
      molecular studies revealed that Lurcher is a gain of function mutation in the
      delta2 glutamate receptor (GluRdelta2) that converts an alanine to threonine in
      the highly conserved third hydrophobic segment of GluRdelta2. The mutation
      converts the receptor into a constitutively leaky cation channel. The GluRdelta2
      receptor is predominantly expressed in cerebellar Purkinje cells and in the
      heterozygous Lurcher mutant (+/Lc). Purkinje cells die due to the mutation in the
      GluRdelta2 receptor, while olivary neurons and granule cells degenerate due to
      the loss of their Purkinje cell targets. The purpose of the review is to provide
      highlights from 5 decades of research on the Lurcher mutant that have provided
      insights into the developmental mechanisms that regulate cell number during
      development, cerebellar pattern formation, cerebellar physiology, and the role of
      the cerebellum in CNS function.

PMID- 16412990
TI  - Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat
      model of Parkinson's disease.
AB  - Recent evidence suggest that the blockade of cannabinoid CB1 receptors might be
      beneficial to alleviate motor inhibition typical of Parkinson's disease (PD). In
      the present study, we have explored the motor effects of rimonabant, a selective
      antagonist of CB1 receptors, in a rat model of PD generated by an
      intracerebroventricular injection of 6-hydroxydopamine. Compared with rats
      subjected to unilateral injection of this toxin in the medial forebrain bundle,
      this model allows nigral dopaminergic neurons be symmetrically affected. Dose
      response studies with 6-hydroxydopamine revealed that the application of 200
      microg per animal caused hypokinetic signs (decreased ambulatory activity,
      increased inactivity, and reduced motor coordination), which paralleled several
      signs of degeneration of nigrostriatal dopaminergic neurons (dopamine depletion
      in the caudate-putamen, and decreased mRNA levels for tyrosine hydroxylase and
      superoxide dismutase-1 and -2 in the substantia nigra). In these conditions, the
      degree of hypokinesia and dopaminergic degeneration may be considered moderate,
      comparable to the disturbances occurring in early and middle stages of PD in
      humans, a period that might be appropriate to test the effects of rimonabant.
      There is also degeneration of other dopaminergic pathways out of the basal
      ganglia, but this does not appear to interfere significantly with the hypokinetic
      profile of these rats. Higher doses of 6-hydroxydopamine elevated significantly
      animal mortality and lower doses failed in general to reproduce motor inhibition.
      Like other animal models of PD, these rats exhibited an increase in the density
      of CB(1) receptors in the substantia nigra, which is indicative of the expected
      overactivity of the cannabinoid transmission in this disease and supports the
      potential of CB1 receptor blockade to attenuate hypokinesia associated with
      nigral cell death. Thus, the injection of 0.1 mg/kg of rimonabant partially
      attenuated the hypokinesia shown by these animals with no effects in control
      rats, whereas higher doses (0.5-1.0 mg/kg) were not effective. We also found that
      the antihypokinetic effects of low doses of rimonabant did not influence the
      dopamine deficits of these animals, as well as it did not modify GABA or
      glutamate transmission in the caudate-putamen. In summary, rimonabant may have
      potential antihypokinetic activity in moderate parkinsonism at low doses, but
      this effect is not related to changes in dopaminergic, GABAergic, or
      glutamatergic transmission in the striatum. Therefore, the elucidation of the
      neurochemical substrate involved in this effect remains a major challenge for the
      future.

PMID- 16412992
TI  - "Fatigue" of medullary but not mesencephalic raphe serotonergic neurons during
      locomotion in cats.
AB  - Single unit activity of presumed serotonergic neurons in the medulla [n. raphe
      obscurus (NRO) and pallidus (NRP)] or the mesencephalon [n. raphe dorsalis (DRN)]
      was recorded in adult male cats during prolonged treadmill locomotion. Treadmill
      speed was set at a moderate level (0.4 m/s) in order to induce long-duration
      locomotion. The typical time to "fatigue" (failure to keep pace, falling behind
      and reluctance to continue) was approximately 40 min in both groups, at which
      point cats typically displayed marked panting and vocalization. The activity of
      DRN neurons was unchanged from baseline during the locomotion trial and during
      the recovery phase. By contrast, the activity of NRO/NRP neurons decreased
      steadily across the locomotion trial, reaching a mean decrease of approximately
      50% (during the first min after the treadmill was turned off). Full recovery of
      single unit activity to a level approximating the baseline discharge rate
      required 30-45 min. Possible mechanisms underlying these changes are discussed as
      is the role of serotonin and fatigue in human pathology.

PMID- 16412994
TI  - Pre-target activity in visual cortex predicts behavioral performance on spatial
      and feature attention tasks.
AB  - Physiological studies in humans and monkeys have revealed that, in response to an
      instruction to attend, areas of sensory cortex that code the attributes of the
      expected stimulus exhibit increases in neural activity prior to the arrival of
      the stimulus. Models of selective visual attention posit that these increases in
      activity give attended stimuli a processing advantage over distracting stimuli.
      Here, we test two key predictions of this view by using functional magnetic
      resonance imaging to record human brain activity during a cued voluntary
      orienting task. First, we tested whether pre-stimulus modulations are observed
      during both cued spatial and cued feature attention. Secondly, we tested whether
      the magnitude of pre-stimulus modulations predicts behavioral performance. Our
      results indicate that cue-triggered expectation of targets with particular
      spatial or nonspatial features activates areas of the visual cortex selective for
      these features. Furthermore, the magnitude of the cue-triggered modulations
      correlated with behavioral measures, such that those subjects who exhibited
      relatively large pre-stimulus modulations of activity performed better on the
      behavioral task. These findings support the view that top-down control systems
      bias activity in sensory cortices to favor the processing of expected target
      features and that this bias is related to behavior.

PMID- 16412995
TI  - Age-dependent measures of anxiety and cognition in male histidine decarboxylase
      knockout (Hdc-/-) mice.
AB  - Histidine decarboxylase deficient (Hdc(-/-)) and wild-type male mice on the
      C57Bl6/J background were used to determine the role of histamine in brain
      function. 3-5 (Y) and 12-14 (MA) month-old Hdc(-/-) mice showed hypoactivity and
      increased measures of anxiety in the open field, light-dark, elevated plus-maze,
      and elevated zero maze tests. Y Hdc(-/-) mice showed superior performance in the
      hidden sessions of the water maze and passive avoidance memory retention. In
      contrast, Y Hdc(-/-) mice were impaired in novel location recognition, spent less
      time searching in the target quadrant and more time searching in the outer zone
      of the water maze during the probe trials. These behaviors are likely due to
      increased measures of anxiety and are not found in MA Hdc(-/-) mice. These data
      support a role for histamine in anxiety and cognition and underline the
      importance of considering age and potential effects on measures of anxiety in the
      interpretation of the role of histaminergic neurotransmission in cognitive
      function.

PMID- 16412997
TI  - Contingency does not contribute to the effects of cocaine self-administration on
      prodynorphin and proenkephalin gene expression in the rat forebrain.
AB  - Neuroadaptations in the brain opioid systems produced by chronic exposure to
      drugs of abuse may contribute to the drug dependence and addiction. Although
      regulation of the gene expression of the opioid propeptides proenkephalin (PENK)
      and prodynorphin (PDYN) by psychostimulants has previously been described, little
      attention has been paid to dissociating effects of pharmacological actions of the
      drugs from those produced by motivational processes driving active drug intake in
      self-administration paradigms. In the present study, effects of response
      dependent (contingent) and response-independent (noncontingent) cocaine
      administration on the PENK and PDYN gene expression in the rat forebrain have
      been directly compared using the "yoked" self-administration procedure. The i.v.
      cocaine treatment lasted for 5 weeks, and rats were sacrificed 24 h after the
      last self-administration session. In situ hybridization analysis revealed that
      levels of the PDYN mRNA were significantly increased in the caudate/putamen, to
      the same extent in rats self-administering cocaine as in animals receiving
      noncontingent injections of the drug at the same frequency and dosage. No changes
      in the expression of the PDYN gene were detected in the nucleus accumbens or in
      the central nucleus of amygdala. Levels of the PENK mRNA remained unaltered in
      all the above-mentioned forebrain regions of rats receiving contingent or
      noncontingent cocaine injections. The obtained data indicate that up-regulation
      of the PDYN gene expression in the caudate/putamen results from direct
      pharmacological actions of cocaine rather than from the motivational and
      cognitive processes underlying active self-administration of the drug.

PMID- 16412996
TI  - Dissociable effects in reaction time performance after unilateral cerebral
      infarction: a comparison between the left and right frontal cortices in rats.
AB  - Reaction time performance reflects the speed of information processing, both in
      humans and lower vertebrates like the rat. The present study compared reaction
      time performance in rats following unilateral infarction to the frontal cortex.
      The objective was to model cognitive impairment as it is seen in humans after
      stroke. Rats were trained in a reaction time paradigm, after which unilateral
      cortical infarction was induced photochemically. Reaction time performance was
      differentially affected after unilateral infarction to either the left or right
      frontal cortex, whereas sham operation did not result in a significant alteration
      in reactivity. An overall increase in reaction time of about 10% was present at 4
      weeks after frontal infarction. In addition, a lateralized reaction time deficit
      occurred very early after right frontal infarction as an increase of 10-15% in
      trials directed towards the contralesional side. Additional analyses showed that
      these reaction time deficits can be explained differently: the former as a
      gradual and general decrease in the speed of information processing, whereas the
      latter shows specific impairment to initiate a contralateral motor response. The
      former matches well with the mental slowing observed in stroke patients, whereas
      the latter resembles a neglect phenomenon. We conclude that measuring reaction
      time performance after frontal cortical infarction in rats could offer a useful
      tool to model particular human cognitive impairments following cerebral
      infarction.

PMID- 16412993
TI  - L-carnitine suppresses the onset of neuromuscular degeneration and increases the
      life span of mice with familial amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by progressive
      degeneration of motor neurons in the spinal cord and motor cortex. Although the
      etiology of ALS remains unknown, a mutation of the gene encoding Cu,Zn-superoxide
      dismutase (SOD1) has been reported in 20% of familial cases of ALS (FALS).
      Transgenic mice that overexpress a mutated human SOD1 exhibit a phenotype and
      pathology similar to those observed in patients with FALS. Mitochondrial
      abnormality has been reported in patients with ALS and in animal models of FALS.
      We recently reported that L-carnitine, an essential cofactor for the beta
      oxidation of long-chain fatty acids, effectively inhibits various types of
      mitochondrial injury and apoptosis both in vitro and in vivo. The present study
      demonstrates that oral administration of L-carnitine prior to disease onset
      significantly delayed the onset of signs of disease (log-rank P=0.0008), delayed
      deterioration of motor activity, and extended life span (log-rank P=0.0001) in
      transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg). More
      importantly, subcutaneous injection of L-carnitine increased the life span of Tg
      mice (46% increase in male, 60% increase in female) even when given after the
      appearance of signs of disease.

PMID- 16412998
TI  - Increased expression of osteopontin in the brain with scrapie infection.
AB  - The expression of osteopontin (OPN) was studied in the brains of mice with
      scrapie. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western
      blot analysis showed that the expression of OPN protein and mRNA was increased
      significantly in the scrapie-infected brains compared to the controls. The
      increased expression of OPN protein was largely matched with the PrP(Sc)
      accumulation. Immunohistochemically, OPN was intensely immunostained in neurons
      of the midbrain at the time of scrapie infection initiation. Particularly, OPN
      immunostaining was noted in the reactive astrocytes and some microglia in the
      scrapie brains, while those cells were devoid of OPN immunoreactivity in control
      brains. Overall, these findings suggest that some neurons affected by PrP(Sc) at
      an early stage of scrapie transiently express OPN but subsequently succumb to
      cell death at a later stage of scrapie; astroglial cells after scrapie infection
      are activated to express OPN; and increased OPN expression in these cells may
      play an important role in the pathology of scrapie. The precise role of OPN in
      scrapie needs further study.

PMID- 16412999
TI  - Semantic and syntactic processing in Chinese sentence comprehension: evidence
      from event-related potentials.
AB  - An ERP experiment was conducted to explore semantic and syntactic processes as
      well as their interplay in Chinese sentence comprehension. Participants were
      auditorily presented with Chinese ba sentences, which were either correct,
      semantically incorrect, syntactically incorrect, or both semantically and
      syntactically incorrect. The syntactic violation, which was created by
      eliminating the object-noun phrase from a preposition-object phrase structure,
      elicited an early starting anterior negativity which merged into a sustained
      negativity over anterior sites and a temporally limited centro-parietal
      negativity. The semantic violation elicited an early starting N400 effect. The
      combined violation in which the syntactic phrase structure violation and the
      semantic violation were crossed elicited an early staring sustained anterior
      negativity similar to the pure syntactic effect, and a centro-parietal negativity
      which was more negative than those of the syntactic condition and the semantic
      condition. No P600 was obtained neither for the syntactic nor for the combined
      condition. The results suggest that the syntactic processes (at about 50 ms)
      appear earlier than the semantic processes (at around 150 ms). They are
      independent from each other in the early time window (150-250 ms) but interact in
      a later processing phase (250-400 ms) during Chinese ba sentence comprehension.
      The broadly distributed negativity, which occurred during the N400 latency range
      observed in the three violation conditions, is thought to reflect thematic
      integration processes in the sentence-final position.

PMID- 16413001
TI  - Differentiation of the fucoidan sulfated L-fucose isomers constituents by CE
      ESIMS and molecular modeling.
AB  - Alpha-L-fucose, the monosaccharide component of fucoidan, is found in the
      polysaccharide mainly as its sulfated form where sulfate groups are in position 2
      and/or 4 and/or 3. The correlation between biological activities and structure of
      fucoidan requires the determination of the sulfation pattern of the fucose
      residues. Therefore, it is of importance to discriminate between the isobaric
      sulfated fucose isomers. For this purpose, the three isomers 2-O-, 3-O-, and 4-O
      sulfated fucose have been analyzed using electrospray ion trap mass spectrometry
      and capillary electrophoresis. The results reported herein show that it is
      possible to differentiate between these three positional isomers of sulfated
      fucose based on their fragmentation pattern upon MS/MS experiments. 3-O-Sulfated
      fucose was characterized by the loss of the hydrogenosulfate anion HSO4- as the
      main fragmentation product, while the two other isomers 2-O-, and 4-O-sulfated
      fucose exhibited cross-ring fragmentation yielding to distinctive (0,2)X and
      (0,2)A daughter ion, respectively. A computational study of the conformation of
      the sulfated fucose isomers was carried out providing an understanding of the
      fragmentation pattern with respect to the position of the sulfate group.

PMID- 16413000
TI  - Two-step regio- and stereoselective syntheses of [19F]- and [18F]-2-deoxy-2-(R)
      fluoro-beta-D-allose.
AB  - Replacement of specific hydroxyl groups by fluorine in carbohydrates is an
      ongoing challenge from chemical, biological, and pharmaceutical points of view. A
      rapid and efficient two-step, regio- and stereoselective synthesis of 2-deoxy-2
      (R)-fluoro-beta-d-allose (2-(R)-fluoro-2-deoxy-beta-d-allose; 2-FDbetaA), a
      fluorinated analogue of the rare sugar, d-allose, is described. TAG (3,4,6-tri-O
      acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol or 3,4,6-tri-O-acetyl-d
      glucal), was fluorinated in anhydrous HF with dilute F(2) in a Ne/He mixture or
      with CH(3)COOF at -60 degrees C. The fluorinated intermediate was hydrolyzed in
      1N HCl and the hydrolysis product was purified by liquid chromatography and
      characterized by 1D (1)H, (13)C, and (19)F NMR spectroscopy as well as 2D NMR
      spectroscopy and mass spectrometry. In addition, (18)F-labeled 2-deoxy-2-(R)
      fluoro-beta-d-allose (2-[(18)F]FDbetaA) was synthesized for the first time, with
      an overall decay-corrected radiochemical yield of 33+/-3% with respect to
      [(18)F]F(2), the highest radiochemical yield achieved to date for electrophilic
      fluorination of TAG. The rapid and high radiochemical yield synthesis of 2
      [(18)F]FDbetaA has potential as a probe for the bioactivity of d-allose.

PMID- 16413003
TI  - Metal-ion interactions with carbohydrates. Crystal structure and FT-IR study of
      the SmCl3-ribose complex.
AB  - A single-crystal of SmCl3.C5H10O5.5H2O was obtained from methanol-water solution
      and its structure determined by X-ray. Two forms of the complex as a pair of
      anomers and related conformers were found in the single-crystal in a disordered
      state. One ligand is alpha-D-ribopyranose in the 4C1 conformation and the other
      one is beta-D-ribopyranose. The anomeric ratio is 1:1. Both ligands provide three
      hydroxyl groups in ax-eq-ax orientation for coordination. The Sm3+ ion is nine
      coordinated with five Sm-O bonds from water molecules, three Sm-O bonds from
      hydroxyl groups of the D-ribopyranose and one Sm-Cl bond. The hydroxyl groups,
      water molecules and chloride ions form an extensive hydrogen-bond network. The IR
      spectral C-C, O-H, C-O, and C-O-H vibrations were observed to be shifted in the
      complex and the IR results are in accord with those of X-ray diffraction.

PMID- 16413002
TI  - Preparation and biological evaluation of some 1,2-O-isopropylidene-D-hexofuranose
      esters.
AB  - The synthesis and biological evaluation of some new glycose esters bearing the
      1,2-O-isopropylidene-d-hexofuranose functionality and belonging to the 3-O-acyl-d
      allose and 6-O-acyl-d-glucose series are reported. When the results concerning
      cell growth inhibition are compared, it appears that the 6-O-acyl-d-glucose
      derivatives are more active than the 3-O-acyl-d-allose compounds. Within both 6-O
      acyl-d-glucose and 3-O-acyl-d-allose derivatives, butyric esters displayed the
      highest inhibitory effects. Inhibition of cell growth is not associated with high
      induction levels of erythroid differentiation, despite the fact that pivaloates
      induce erythroid differentiation to an extent similar to that exhibited by
      previously reported molecules [Bioorg. Med. Chem. Lett.1999, 9, 3153-3158].

PMID- 16413004
TI  - The importance of estimating the therapeutic index in the development of matrix
      metalloproteinase inhibitors.
AB  - At least 56 matrix metalloproteinase (MMP) inhibitors have been pursued as
      clinical candidates since the late 1970's when the first drug discovery program
      targeting this enzyme family began. Some of these clinical candidates were
      pursued for multiple indications. However, the two primary indications that have
      been targeted are cancer (24 drugs) and anti-arthritis (27 drugs). Cardiovascular
      disease was listed as an indication for 10 drugs. Forty-six MMP inhibitors have
      been discontinued, 7 remain in clinical development, and only 1 (Periostat for
      periodontal disease) has been approved. Recently, negative phase II results were
      reported for the MMP inhibitor PG-116800, which was being evaluated as a
      treatment for post-ischemic myocardial remodeling to prevent heart failure. One
      major factor leading to the failure of PG-116800 and many of the other MMP
      inhibitors is the inadequate assessment of the therapeutic index, the ratio of
      dose required for efficacy vs. that for toxicology. This review describes the
      dose-limiting side effect that has hampered MMP inhibitor development (the
      musculoskeletal syndrome), cardiovascular clinical MMP inhibitor studies, a model
      of the therapeutic index using marimastat, and progress towards more selective
      MMP inhibitors not limited by the musculoskeletal syndrome.

PMID- 16413005
TI  - Polychlorobiphenylols are selective inhibitors of human phenol sulfotransferase
      1A1 with 4-nitrophenol as a substrate.
AB  - Polychlorobiphenylols (OH-PCBs) were reported as potent inhibitors of estrogen
      sulfotransferase, thyroid hormone and 3-hydroxybenzo(a)pyrene sulfotransferases.
      The aim of this study was to examine the effects of selected OH-PCBs on SULT1A1
      activity in human liver cytosol, measured with 4microM 4-nitrophenol, a
      concentration considered to be diagnostic for selectively detecting SULT1A1. All
      the OH-PCBs studied inhibited the sulfonation of 4-nitrophenol in human liver
      cytosol. Among the eighteen OH-PCBs studied, 3'-OH-CB3 (4-chlorobiphenyl-3'-ol)
      was the most potent inhibitor (IC(50): 0.73+/-0.15microM, mean+/-S.D., n=3). The
      least potent inhibitor studied was 6'-OH-CB35 (3,3',4-trichlorobiphenyl-6'-ol)
      with IC(50): 49.1+/-10.8microM. The IC(50) values of the other OH-PCBs studied
      ranged from 0.78 to 3.76microM. Some OH-PCBs with various inhibitory potencies
      with human liver cytosol were selected for study with recombinant human SULT1A1
      and SULT1B1. These OH-PCBs showed more potent inhibition of 4-nitrophenol
      sulfonation with SULT1A1 than with human liver cytosol. The IC(50) values with
      human liver cytosol showed a perfect linear correlation with those found with
      SULT1A1 (r(2)=1), but not with SULT1B1 (r(2)=0.21). The results suggested that in
      these human samples SULT1A1 was predominantly responsible for the sulfonation of
      4-nitrophenol, with very little or no contribution from SULT1B1. The kinetics of
      inhibition were studied with 4'-OH-CB165, which is similar in structure to OH
      PCBs found in human blood. The 4'-OH-CB165 was a mixed noncompetitive
      uncompetitive inhibitor (K(i)=1.80+/-0.2microM, K(ies)=0.16+/-0.02microM).
      Finally, it was demonstrated that the tested OH-PCBs were themselves only slowly
      sulfonated by human sulfotransferases in the presence of (35)S-PAPS, as measured
      by the production of (35)S-labeled metabolites. Although this series of 18 OH
      PCBs was too small to draw conclusions about structure-potency relationships,
      this work demonstrated that several OH-PCBs were potent inhibitors of 4
      nitrophenol sulfonation but poor substrates in human liver cytosol, and suggested
      that OH-PCBs may inhibit the sulfation rate of those xenobiotics sulfated by
      SULT1A1.

PMID- 16413006
TI  - Effects of microcystins over short- and long-term memory and oxidative stress
      generation in hippocampus of rats.
AB  - Microcystins produced by cyanobacteria are potent inhibitors of some protein
      phosphatases, but recent evidence also indicates its potential to generate
      oxidative stress. In the present study, the effects of microcystin raw extracts
      (Mic; 0.01 and 20microg/L) and purified okadaic acid (OA; 0.01 and 10microg/L) on
      short- and long-term memory alteration and antioxidant and oxidative damage were
      investigated in hippocampus of rats. The results showed an amnesic effect with
      0.01 and 20microg/L Mic on retrieval and only with 0.01microg/L Mic on spatial
      learning. Parallel to these effects oxidative damage was observed as evidenced by
      augmented levels of lipid peroxides and DNA damage and the absence of antioxidant
      responses in terms of total oxyradical scavenging capacity. Phase II reactions
      catalyzed by glutathione-S-transferase were not modified after microcystins
      exposure. Overall this study showed physiological events (retrieval and spatial
      learning) that can be related to the classical toxic effects of microcystins
      (i.e., phosphatase inhibition). In addition, evidence of alternative toxicity
      mechanisms via oxidative stress generation was also obtained. The fact that
      organic anion transporter polypeptides (OATP) involved in microcystins uptake are
      expressed not only in liver but also in brain points to the environmental
      relevance of the observed effects.

PMID- 16413007
TI  - Bovine papillomavirus type 1 oncoprotein E5 stimulates the utilization of
      superoxide radicals in the mouse fibroblast cell line C127.
AB  - The major transforming protein of bovine papillomavirus type 1 (BPV-1) is a small
      hydrophobic polypeptide, the E5 gene product, localized in the cellular membranes
      and modulating various pathways in the cell. Many studies have shown that
      reactive oxygen species (ROS) are essential in several biological processes,
      including cell transformation by oncogenes, but unregulated ROS are highly toxic
      to cells. We studied the effect of the bovine papillomavirus protein E5 and its
      mutants on the level of the superoxide radicals in the mouse fibroblast cell line
      C127. The superoxide level in C127 cells transfected with the E5-expressing
      plasmids were measured by nitroblue tetrazolium reduction. Relative
      concentrations of intracellular peroxide were determined by using 2,7
      dichlorofluorescin diacetate. Our results showed that all transforming mutants of
      E5 reduced the level of superoxide in C127 cells, besides the activity of
      superoxide dismutase (SOD) and level of peroxides was not altered. In the
      presence of neopterin, an inhibitor of the superoxide-producing enzymes, the
      reduction of superoxide level correlated with the transforming ability of the E5
      mutants. The inhibitor of the protein tyrosine kinase, tyrphostin 25 and
      inhibitors of oxygenases of the arachidonic acid metabolism, aspirin and
      nordihydroguaiaretic acid, blocked the effect of BPV-1 E5. We conclude that BPV-1
      E5 and its transforming mutants are able to modulate the level of superoxide and
      stimulate the utilization of superoxide through protein tyrosine kinases and
      oxygenases of the arachidonic acid metabolism.

PMID- 16413008
TI  - The use of a hospital laboratory cohort to estimate the prevalence of
      dyslipidemia in an adult Brazilian population.
AB  - BACKGROUND: Dyslipidemia is diagnosed through the determination of plasma lipid
      profiles. This study is aimed at establishing the prevalence of dyslipidemia in a
      Brazilian out-patient population by using a hospital laboratory cohort. METHODS:
      Lipid profiles of 22,542 individuals from both sexes, aged 20 to 124 years, and
      registered at the University Hospital of the State University of Campinas, a
      standard of reference for hospital treatment in the state of Sao Paulo, Brazil,
      were retrospectively analyzed from 2000 to 2003. The cut-off values for
      cholesterol (C), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C)
      and high-density lipoprotein-cholesterol (HDL-C) were determined as recommended
      by the National Cholesterol Education Program. Statistical analyses were carried
      out using the SPSS program. RESULTS: Altered C, LDL-C and TG were found in 44%,
      38% and 37% of adults and in 55%, 48% and 41% of the elderly, respectively; 35%
      of adults and 32% of the elderly presented undesirable low HDL-C. Combined
      dyslipidemia was very prevalent. CONCLUSION: Dyslipidemia was a serious public
      health problem in the studied population, especially among women and the elderly.
      The mixed phenotype of hypercholesterolemia and hypertriglyceridemia was the most
      prevalent. The results of this study were validated by their agreement with
      previously studied non-hospital Brazilian populations.

PMID- 16413009
TI  - Evaluation of the VITROS chemistry products dHDL slides for direct measurement of
      high density lipoprotein cholesterol.
AB  - BACKGROUND: We evaluated the new VITROS direct high density lipoprotein
      cholesterol (dHDL) slide assay, based on the precipitation of apolipoprotein B
      containing lipoproteins by phosphotungstic acid/magnesium chloride (PTA/MgCl2).
      METHODS: We determined linearity, within-run and between-run imprecision for the
      VITROS dHDL slide assay, and compared it to the RANDOX two-step PTA/MgCl2 method
      for 300 fresh sera. Moreover, triglyceride and cholesterol interference were
      tested. RESULTS: The VITROS dHDL slide assay was linear from 0 to 3.13 mmol/l.
      Within-run and between-run imprecision were 1.6%, 1.8%, 3.3% and 3.2% for target
      values at 1.00 and 1.40 mmol/l, respectively. For 300 fresh serum samples, the
      linear regression equation between the VITROS dHDL slide assay (y) and the RANDOX
      PTA/MgCl2 2 method (x) was: y (mmol/l)=0.934 x+0.043 (CI=0.916-0.952 for slope
      and 0.017-0.069 for intercept) . The bias of the VITROS assay compared to the
      RANDOX PTA/MgCl2 method was less than 5% for HDL cholesterol concentrations used
      for medical decision (1.04 and 1.50 mmol/l). Total error remained below 13% for
      triglyceride and LDL cholesterol concentrations below 6.6 mmol/l. CONCLUSION: The
      VITROS dHDL slide assay is rapid, linear over a broad range of concentrations,
      and satisfies the National Cholesterol Education Program goals for precision and
      accuracy.

PMID- 16413010
TI  - CYP2C9 polymorphism and warfarin sensitivity in Taiwan Chinese.
AB  - BACKGROUND: Warfarin prevents thromboembolism in patients with prosthetic heart
      valvular replacement. Cytochrome P4502C9 (CYP2C9) is polymorphic in human and is
      principally responsible for the metabolism of warfarin. However, known CYP2C9
      polymorphisms cannot entirely account for the low dose requirement of warfarin in
      Chinese-Taiwanese receiving mitral valve replacement. We screened a new
      polymorphism of CYP2C9 and investigated its role in warfarin sensitivity.
      METHODS: We examined warfarin dose requirements in 239 Chinese-Taiwanese patients
      who had attended a cardiac surgery clinic in National Taiwan University Hospital.
      DNA samples were obtained from 106 Chinese-Taiwanese (37 patients and 69
      unrelated healthy controls), and healthy control subjects of Caucasians (n=28)
      and African-Americans (n=28). Four out of those 37 patients were poor
      metabolizers of warfarin, and their DNA were subjected to sequencing analysis.
      Moreover, CYP2C9 genotyping analyses were performed using PCR-RFLP analysis. The
      chi2 test and Fisher's exact test were used to compare the differences of the
      allelic frequency and genotype. The association between warfarin dose requirement
      and genetic polymorphism of CYP2C9 was also analysed. RESULTS: The mean daily
      warfarin dose was 3.11+/-1.62 mg for the maintenance of the international
      normalized ratio of 2 to 3 in 239 patients. A single nucleotide substitution from
      G to C was found in this study. This SNP, G-65/C, is in intron 3, 65 base pairs
      upstream of exon 4. The allelic frequencies of C-65 in healthy controls were
      0.125, 0.058 and approximately 0 with respect to African-American, Chinese
      Taiwanese and Caucasian, implying inter-ethnic variations of the C-65 allele. In
      addition, patients who were carrier of either the heterozygous or homozygous C-65
      variant received half of the usual warfarin dose. CONCLUSION: The novel intronic
      G-65/C mutation appears to be inter-racially different in allelic frequency, and
      that the anticoagulation was affected in response to warfarin sensitivity in
      Chinese-Taiwanese patients receiving mitral valve replacement.

PMID- 16413011
TI  - Drugs of abuse testing in meconium.
AB  - Prenatal substance abuse is an ongoing concern with significant impact on
      neonatal health and development across socioeconomic lines. Meconium, passed by
      neonates during their first post-natal bowel movements, is a matrix unique to the
      developing fetus and contains a long history of prenatal metabolism. Over the
      last two decades, the use of meconium as a matrix for assessing prenatal exposure
      to drugs of abuse has yielded methods exhibiting higher sensitivity, easier
      collection, and a larger window of detection than traditional matrices. Recently,
      a method has been developed for the analysis of fatty acid ethyl esters in
      meconium as a biomarker of fetal alcohol exposure, potentially facilitating the
      future diagnosis of Fetal Alcohol Spectrum Disorder in situations where
      gestational alcohol consumption history is unknown. Screening for prenatal
      exposure to illicit and abused licit drugs in meconium is possible by use of a
      variety of immunoassay methods with conformational analysis usually occurring by
      GCMS or LCMS. In spite of increased sample preparation time relative to blood and
      urine, the long metabolic history, coupled with the ease and wide window of
      collection of meconium make it the ideal matrix for determining fetal drug
      exposure.

PMID- 16413014
TI  - Cumulative semantic inhibition in picture naming: experimental and computational
      studies.
AB  - We report an experiment in which subjects named 120 pictures, consisting of
      series of five pictures drawn from each of 24 semantic categories (and intermixed
      with 45 fillers). The number of intervening trials (lag) between successive
      presentations of members of the same category varied from two to eight. Subjects'
      naming latencies were slowed by 30 ms for each preceding member of the category.
      This effect was both cumulative and linear, and unrelated to the lag elapsing
      since the previous presentation of a category member. These results definitively
      demonstrate the occurrence of cumulative interference for word retrieval by prior
      retrieval of other exemplars of the same semantic category-cumulative semantic
      inhibition. We claim that this inhibition effect could only occur if the spoken
      word production system possesses three specific properties (competition, priming,
      and sharing of semantic activation). We provide computational-modelling evidence
      in support of this claim. We show that no current theory of spoken word
      production has all of these properties. In their current form, all these theories
      are falsified by these results. We briefly discuss the obstacles that may be
      encountered by current models were they modified to account for our findings.

PMID- 16413013
TI  - Detecting exon deletions and duplications of the DMD gene using Multiplex
      Ligation-dependent Probe Amplification (MLPA).
AB  - OBJECTIVES: To evaluate the efficacy of Multiplex Ligation-dependent Probe
      Amplification (MLPA) technique in comparison with the traditional multiplex PCR
      assay in detection of exon deletions and duplications of the DMD gene. DESIGN AND
      METHODS: The sensitivity and accuracy of MLPA were assessed and compared with the
      multiplex PCR in a total of 63 subjects including 43 subjects with Duchenne
      muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) and 20 female
      carriers. RESULTS: MLPA was able to detect all the known deletions and
      duplications; it detected four additional mutations that had been missed by
      multiplex PCR. In addition, the extent of the deletions and duplications could be
      more accurately defined which in turn facilitated a genotype-phenotype
      correlation. CONCLUSIONS: MLPA is superior to multiplex PCR. It should be the
      method of choice for the detection of exon deletions and duplications of the DMD
      gene in patients with DMD or BMD, as well as in female carriers.

PMID- 16413012
TI  - Oxidative stress and antioxidant status in non-metastatic prostate cancer and
      benign prostatic hyperplasia.
AB  - OBJECTIVES: We undertook the present study to investigate the possible alteration
      of oxidant/antioxidant status in the circulation of patients with prostate cancer
      and benign prostatic hyperplasia. DESIGN AND METHODS: Thiobarbituric acid
      reactive substances (TBARS), the enzyme activities of superoxide dismutase (SOD),
      glutathione peroxidase (GPX), catalase (CAT) and copper (Cu) and zinc (Zn) levels
      were estimated in the erythrocytes of 25 non-metastatic prostate cancer patients,
      36 benign prostatic hyperplasia (BPH) patients and 24 age- and sex-matched
      healthy subjects (controls). RESULTS: TBARS concentrations were significantly
      increased, while erythrocyte GPX and SOD activities were significantly decreased
      in the prostate cancer group versus controls (P < 0.001) and BPH group (P <
      0.05). Zn levels were lowered in prostate cancer patients versus controls (P <
      0.01) with no significant changes between BPH and cancer groups. Similarly, lipid
      peroxidation was increased (P < 0.05) with decreased SOD activity and Zn level (P
      < 0.05) in BPH versus controls. CONCLUSION: These results reveal an alteration in
      the lipid peroxidation index, with concomitant changes in the antioxidant defense
      system in prostate cancer patients compared to BPH patients. We hypothesize that
      an altered prooxidant-antioxidant balance may lead to an increase in oxidative
      damage and consequently may play an important role in prostate carcinogenesis.

PMID- 16413015
TI  - Effect of the anti-anginal agent, perhexiline, on neutrophil, valvular and
      vascular superoxide formation.
AB  - The prophylactic anti-anginal agent, perhexiline, may also be effective in acute
      coronary syndromes and advanced aortic valvular stenosis, conditions associated
      with enhanced inflammation. Its potential effects on superoxide formation via
      NADPH oxidase were measured by lucigenin-mediated chemiluminescence. Perhexiline
      inhibited superoxide formation in intact neutrophils stimulated with formyl Met
      Leu Phe (fMLP) 4 muM or with phorbol myristate acetate (PMA) 162 nM - IC50 2.3
      microM (1.5-3.6), n=4. Sub-unit assembly of NADPH oxidase by PMA was unaffected
      by pretreatment with perhexiline 2 microM, a concentration which reduced
      superoxide formation by 44+/-5% (n=4) in intact neutrophils. Perhexiline
      inhibited preassembled neutrophil NADPH oxidase and that in membranes of pig
      valve interstitial cells, human umbilical vein endothelial cells (HUVECs) and
      cardiac fibroblasts, but not that in rat aorta (rings or membrane preparations).
      These data imply that perhexiline inhibits the phagocytic NADPH oxidase directly,
      and that pig aortic valvular interstitial cells possess a similar enzyme, a
      conclusion supported by immunohistochemical localisation of the gp91phox subunit
      in these cells. However further study is required to clarify the effect of
      perhexiline on different NADPH oxidase isoforms particularly in the vasculature.

PMID- 16413019
TI  - Schistosoma mekongi: the in vitro effect of praziquantel and artesunate on the
      adult fluke.
AB  - The efficacy and tolerance of 80 microg/ml praziquantel (PZQ) and 40 microg/ml
      artesunate (ATS) against adult stage Schistosoma mekongi in vitro were
      investigated after 3, 6, 12, and 24h incubation by monitoring worm motility and
      compared tegumental changes using scanning electron microscopy (SEM). Thirty mice
      were infected with S. mekongi cercaria for 49 days. Adult worms were collected by
      perfusion method and prepared for in vitro study. Contraction and decreased motor
      activity were observed after as little as 3h incubation with PZQ and ATS. Some of
      the worms were immobile 12h after exposure, and died within 24h. The tegument of
      S. mekongi showed severe swelling, vacuolization and disruption, fusion of the
      tegumental ridges, collapse and peeling. After 12-24h incubation, PZQ induced
      similar but they less severe, tegumental changes to those observed after exposure
      to ATS. The direct observation of the fluke motility and SEM study suggest that
      ATS is more effective than PZQ in causing tegumental damage in adult S. mekongi,
      and provides a basis for subsequent clinical trials.

PMID- 16413017
TI  - Cyclic AMP regulates the expression and nuclear translocation of RFC40 in MCF7
      cells.
AB  - We have previously shown that the regulatory subunit of PKA, RIalpha, functions
      as a nuclear transport protein for the second subunit of the replication factor C
      complex, RFC40, and that this transport appears to be crucial for cell cycle
      progression from G1 to S phase. In this study, we found that N(6)-monobutyryl
      cAMP significantly up-regulates the expression of RFC40 mRNA by 1.8-fold and its
      endogenous protein by 2.3-fold with a subsequent increase in the RIalpha-RFC40
      complex formation by 3.2-fold. Additionally, the nuclear to cytoplasmic ratio of
      RFC40 increased by 26% followed by a parallel increase in the percentage of S
      phase cells by 33%. However, there was reduction in the percentage of G1 cells by
      16% and G2/M cells by 43% with a concurrent accumulation of cells in S phase.
      Interestingly, the higher percentage of S phase cells did not correlate with a
      parallel increase in DNA replication. Moreover, although cAMP did not affect the
      expression of the other RFC subunits, there was a significant decrease in the
      RFC40-37 complex formation by 81.3%, substantiating the decrease in DNA
      replication rate. Taken together, these findings suggest that cAMP functions as
      an upstream modulator that regulates the expression and nuclear translocation of
      RFC40.

PMID- 16413018
TI  - PHTS, a novel putative tumor suppressor, is involved in the transformation
      reversion of HeLaHF cells independently of the p53 pathway.
AB  - HeLaHF is a non-transformed revertant of HeLa cells, likely resulting from the
      activation of a putative tumor suppressor(s). p53 protein was stabilized in this
      revertant and reactivated for certain transactivation functions. Although p53
      stabilization has not conclusively been linked to the reversion, it is clear that
      the genes in p53 pathway are involved. The present study confirms the direct role
      of p53 in HeLaHF reversion by demonstrating that RNAi-mediated p53 silencing
      partially restores anchorage-independent growth potential of the revertant
      through the suppression of anoikis. In addition, we identified a novel gene,
      named PHTS, with putative tumor suppressor properties, and showed that this gene
      is also involved in HeLaHF reversion independently of the p53 pathway. Expression
      profiling revealed that PHTS is one of the genes that is up-regulated in HeLaHF
      but not in HeLa. It encodes a putative protein with CD59-like domains. RNAi
      mediated PHTS silencing resulted in the partial restoration of transformation
      (anchorage-independent growth) in HeLaHF cells, similar to that of p53 gene
      silencing, implying its tumor suppressor effect. However, the observed increased
      transformation potential by PHTS silencing appears to be due to an increased
      anchorage-independent proliferation rate rather than suppression of anoikis,
      unlike the effect of p53 silencing. p53 silencing did not affect PHTS gene
      expression, and vice versa, suggesting PHTS may function in a new and p53
      independent tumor suppressor pathway. Furthermore, over-expression of PHTS in
      different cancer cell lines, in addition to HeLa, reduces cell growth likely via
      induced apoptosis, confirming the broad PHTS tumor suppressor properties.

PMID- 16413016
TI  - Phenotypic characterization of telomerase-immortalized primary non-malignant and
      malignant tumor-derived human prostate epithelial cell lines.
AB  - In vitro human prostate cell culture models are critical for clarifying the
      mechanism of prostate cancer progression and for testing preventive and
      therapeutic agents. Cell lines ideal for the study of human primary prostate
      tumors would be those derived from spontaneously immortalized tumor cells;
      unfortunately, explanted primary prostate cells survive only short-term in
      culture, and rarely immortalize spontaneously. Therefore, we recently have
      generated five immortal human prostate epithelial cell cultures derived from both
      the benign and malignant tissues of prostate cancer patients with telomerase, a
      gene that prevents cellular senescence. Examination of these cell lines for their
      morphologies and proliferative capacities, their abilities to grow in low serum,
      to respond to androgen stimulation, to grow above the agar layer, to form tumors
      in SCID mice, suggests that they may serve as valid, useful tools for the
      elucidation of early events in prostate tumorigenesis. Furthermore, the
      chromosome alterations observed in these immortalized cell lines expressing
      aspects of the malignant phenotypes imply that these cell lines accurately
      recapitulate the genetic composition of primary tumors. These novel in vitro
      models may offer unique models for the study of prostate carcinogenesis and also
      provide the means for testing both chemopreventive and chemotherapeutic agents.

PMID- 16413020
TI  - Catechin derivatives: specific inhibitor for caspases-3, 7 and 2, and the
      prevention of apoptosis at the cell and animal levels.
AB  - Tea-catechin derivatives are shown to inhibit activities of caspases-3, 2 and 7
      in vitro, and prevented experimental apoptosis at the cell and animal levels.
      Epigallo-catechin-gallate showed the strongest inhibition at 1 x 10(-7)M to these
      caspases, but cysteine cathepsins and caspase-8 were not inhibited. Caspase-3
      inhibition showed a 2nd-order allosteric-type, but the inhibition of caspases-2
      and 7 showed a non-competitive-type. The apoptosis-test using cultured HeLa cells
      was inhibited by these catechins. In rat hepatocytes, apoptosis was induced by d
      galactosamine in vivo. In this case, caspase-3 activity in the cytoplasm, the
      serum aminotransferases and dUTP nick formation detected by TUNNEL-staining were
      effects, and these elevations were suppressed by administration of catechin.

PMID- 16413021
TI  - Novel 2D maps and coupling numbers for protein sequences. The first QSAR study of
      polygalacturonases; isolation and prediction of a novel sequence from Psidium
      guajava L.
AB  - The development of 2D graph-theoretic representations for DNA sequences was very
      important for qualitative and quantitative comparison of sequences. Calculation
      of numeric features for these representations is useful for DNA-QSAR studies.
      Most of all graph-theoretic representations identify each one of the four bases
      with a unitary walk in one axe direction in the 2D space. In the case of
      proteins, twenty amino acids instead of four bases have to be considered. This
      fact has limited the introduction of useful 2D Cartesian representations and the
      corresponding sequences descriptors to encode protein sequence information. In
      this study, we overcome this problem grouping amino acids into four groups: acid,
      basic, polar and non-polar amino acids. The identification of each group with one
      of the four axis directions determines a novel 2D representation and numeric
      descriptors for proteins sequences. Afterwards, a Markov model has been used to
      calculate new numeric descriptors of the protein sequence. These descriptors are
      called herein the sequence 2D coupling numbers (zeta(k)). In this work, we
      calculated the zeta(k) values for 108 sequences of different polygalacturonases
      (PGs) and for 100 sequences of other proteins. A Linear Discriminant Analysis
      model derived here (PG=5.36.zeta1-3.98.zeta3-42.21) successfully discriminates
      between PGs and other proteins. The model correctly classified 100% of a subset
      of 81 PGs and 75 non-PG proteins sequences used to train the model. The model
      also correctly classified 51 out of 52 (98.07%) of proteins sequences used as
      external validation series. The uses of different group of amino acids and/or
      axes orientation give different results, so it is suggested to be explored for
      other databases. Finally, to illustrates the use of the model we report the
      isolation and prediction of the PG action for a novel sequence (AY908988)
      isolated by our group from Psidium guajava L. This prediction coincides very well
      with sequence alignment results found by the BLAST methodology. These findings
      illustrate the possibilities of the sequence descriptors derived for this novel
      2D sequence representation in proteins sequence QSAR studies.

PMID- 16413023
TI  - Widespread tissue distribution and diverse functions of corticotropin-releasing
      factor and related peptides.
AB  - Peptides of the corticotropin-releasing factor (CRF) family are expressed
      throughout the central nervous system (CNS) and in peripheral tissues where they
      play diverse roles in physiology, behavior, and development. Current data
      supports the existence of four paralogous genes in vertebrates that encode CRF,
      urocortin/urotensin 1, urocortin 2 or urocortin 3. Corticotropin-releasing factor
      is the major hypophysiotropin for adrenocorticotropin, and also functions as a
      thyrotropin-releasing factor in non-mammalian species. In the CNS, CRF peptides
      function as neurotransmitters/neuromodulators. Recent work shows that CRF
      peptides are also expressed at diverse sites outside of the CNS in mammals, and
      we found widespread expression of CRF and urocortins, CRF receptors and CRF
      binding protein (CRF-BP) genes in the frog Xenopus laevis. The functions of CRF
      peptides expressed in the periphery in non-mammalian species are largely
      unexplored. We recently found that CRF acts as a cytoprotective agent in the X.
      laevis tadpole tail, and that the CRF-BP can block CRF action and hasten tail
      muscle cell death. The expression of the CRF-BP is strongly upregulated in the
      tadpole tail at metamorphic climax where it may neutralize CRF bioactivity, thus
      promoting tail resorption. Corticotropin-releasing factor and urocortins are also
      known to be cytoprotective in mammalian cells. Thus, CRF peptides may play
      diverse roles in physiology and development, and these functions likely arose
      early in vertebrate evolution.

PMID- 16413022
TI  - Characterization and inhibitor discovery of one novel malonyl-CoA: acyl carrier
      protein transacylase (MCAT) from Helicobacter pylori.
AB  - Type II fatty acid synthesis (FAS II) is an essential process for bacteria
      survival, and malonyl-CoA:acyl carrier protein transacylase (MCAT) is a key
      enzyme in FAS II pathway, which is responsible for transferring the malonyl group
      from malonyl-CoA to the holo-ACP by forming malonyl-ACP. In this work, we
      described the cloning, characterization and enzymatic inhibition of a new MCAT
      from Helicobacter pylori strain SS1 (HpMCAT), and the gene sequence of HpfabD was
      deposited in the GenBank database (Accession No. AY738332 ). Enzymatic
      characterization of HpMCAT showed that the K(m) value for malonyl-CoA was 21.01+/
      2.3 microM, and the thermal- and guanidinium hydrochloride-induced unfolding
      processes for HpMCAT were quantitatively investigated by circular dichroism
      spectral analyses. Moreover, a natural product, corytuberine, was discovered to
      demonstrate inhibitory activity against HpMCAT with IC(50) value at 33.1+/-3.29
      microM. Further enzymatic assay results indicated that corytuberine inhibits
      HpMCAT in an uncompetitive manner. To our knowledge, this is the firstly reported
      MCAT inhibitor to date. This current work is hoped to supply useful information
      for better understanding the MCAT features of H. pylori strain, and corytuberine
      might be used as a potential lead compound in the discovery of the antibacterial
      agents using HpMCAT as target.

PMID- 16413024
TI  - Uncemented Austin-Moore and cemented Thompson unipolar hemiarthroplasty for
      displaced fracture neck of femur--comparison of complications and patient
      satisfaction.
AB  - Austin-Moore and Thompson monobloc prostheses are both commonly used for
      hemiarthroplasty for displaced fractures of the neck of femur in adults. There is
      an ongoing debate about, which of these prostheses should be preferred. We
      present a comparison of two groups of patients with this fracture treated using
      cemented Thompson prosthesis and uncemented Austin-Moore prosthesis. Mortality,
      morbidity and patient satisfaction in the two groups were compared. Cemented
      Thompson hemiarthroplasty was associated with significantly better patient
      satisfaction scores. There was no difference in the mortality rates and hospital
      stay. Patients preferred cemented unipolar Thompson hemiarthroplasty over the
      uncemented unipolar Austin-Moore hemiarthroplasty. A larger randomised
      prospective trial is needed to confirm this finding.

PMID- 16413025
TI  - Treatment of distal tibial metaphyseal fractures: Plating versus shortened
      intramedullary nailing.
AB  - BACKGROUND: Fractures in the distal tibial metaphysis are more complicated to
      treat than diaphyseal fractures. We compared treatment with plating to treatment
      with shorted intramedullary (IM) nailing. METHODS: Patients with AO type 43A
      fractures were treated with plate fixation (group A, n=14) or shortened IM
      nailing (group B, n = 13). We compared postoperative radiographic deformities,
      functional results (Iowa ankle scores), and symptoms (Olerud and Molander ankle
      scores). RESULTS: All fractures had healed at final follow-up (mean, 33 month).
      Mean union times were 27.8 week (range, 18-36 week) in group A and 22.6 week
      (range, 18-30 week) in group B (P<0.05). Mean postoperative valgus angulations
      were larger in group B (3.7 degrees ) than in group A (0.5 degrees ) (P<0.05).
      However, malunions did not differ between groups (P<0.05). Functional results and
      postoperative symptoms were similar. CONCLUSIONS: Both plate fixation and
      shortened IM nailing were effective for treating distal tibial metaphyseal
      fractures.

PMID- 16413026
TI  - Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal
      hyperplasia after balloon injury in rat carotid artery.
AB  - Vascular inflammation induced by the proinflammatory cytokine/NF-kappaB pathway
      is one of the key mechanisms in the development of neointimal hyperplasia.
      Accumulating evidence suggests that a recently identified chemokine, fractalkine,
      is involved in arterial inflammation and atherogenesis. However, no study has
      examined the expression of neointimal fractalkine and the effects of
      pharmacological agents on this process. The purposes of this study were to
      measure neointimal fractalkine expression in the rat carotid artery following
      balloon injury and to determine if alpha-lipoic acid (ALA) inhibits fractalkine
      expression and neointimal hyperplasia. Balloon injury of the rat carotid artery
      induced fractalkine expression in the medial as well as neointimal regions. ALA
      inhibited this expression and consequently prevented neoinitmal hyperplasia in a
      balloon-injured rat carotid artery. Additionally, ALA inhibited TNF-alpha
      stimulated fractalkine expression in cultured vascular smooth muscle cells
      (VSMCs), a process which is mediated through the NF-kappaB pathway. In addition
      to fractalkine, ALA successfully inhibited TNF-alpha-stimulated expression of
      vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 in cultured
      VSMCs. These data suggest that the cytokine-fractalkine system is involved in the
      pathogenesis of restenosis. The present study supports the possibility that ALA,
      which inhibits the NF-kappaB/fractalkine pathway, may be used to prevent
      neointimal hyperplasia after angioplasty or stenting.

PMID- 16413027
TI  - A membrane method for degassing nonaqueous liquids.
AB  - Degassing of nonaqueous solvents is useful for their applications in chemical
      synthesis and in maintaining purity (against oxidative degradation) during long
      term storage. In addition, degassed solvents have been found to be of value in
      the production of oil and water emulsions. Currently, there are three main
      methods for degassing solvents. These are the freeze-pump-thaw process, partial
      degassing using sonication under slight vacuum and purging, where one active gas
      (usually oxygen) is replaced with an inert gas (e.g., nitrogen). In this work we
      have demonstrated the potential application of hollow-fibre membranes to
      efficiently degas water-immiscible, hydrophobic liquids. Mixtures of dodecane and
      water, separately degassed using membranes, show an enhanced dispersion of
      dodecane, similar to that previously reported for freeze-thaw degassed mixtures.

PMID- 16413029
TI  - Mercaptoethane sulfonate protected, water-soluble gold and silver nanoparticles:
      Syntheses, characterization and their building multilayer films with polyaniline
      via ion-dipole interactions.
AB  - Mercaptoethane sulfonate protected, water-soluble gold and silver nanoparticles
      (Au-MES and Ag-MES) are synthesized by one-phase method and characterized by TEM,
      TGA and XPS techniques, UV-vis and FTIR spectra. Both Au-MES and Ag-MES
      nanoparticles are soluble in the water up to 2.0 mg/ml and the stability of Au
      MES is much better than that of Ag-MES. When dissolved in the water, they behave
      like a polyanion and can be used to build multilayer films with polyaniline
      (PANI) by way of layer-by-layer. A new approach is presented to fabricate the
      multilayer films of Au-MES/PANI and Ag-MES/PANI. The assembly mechanism of these
      multilayer films is also discussed. We anticipate highly conducting PANI films
      can be obtained by doping with these nanoparticles.

PMID- 16413028
TI  - Action mechanism of water soluble ethanol on phospholipid monolayers using a
      quartz crystal oscillator.
AB  - Interaction between phospholipid monolayers (dihexadecyl phosphate: DHP,
      dipalmitoyl phosphatidyl choline: DPPC) and water soluble ethanol has been
      studied using quartz crystal microbalance (QCM) method and quartz crystal
      impedance (QCI) method. The quartz crystal oscillator was attached horizontally
      on the DHP and DPPC monolayers that were formed on the water surface. At low
      concentration, increased ethanol concentration decreased the frequency for QCM
      and increased the resistance for QCI. Both frequency and resistance approached
      asymptotically to a saturation value. A further increase in ethanol concentration
      induced a sudden and discontinuous linear change (a decrease in frequency and an
      increase in resistance). Based on these results, we propose the following action
      mechanism of ethanol on phospholipid monolayers: at low concentration, the
      ethanol hydrates adsorb into the monolayer/water interface and saturate on the
      interface. The monolayer viscosity also increases with the adsorption of
      hydrates. A further increase in concentration causes multilayer formation of
      hydrates and/or penetration of hydrates into the monolayer core. The viscosity of
      the interfacial layer (monolayer and interfacial structured water) changes
      dramatically according to the action of ethanol hydrates.

PMID- 16413030
TI  - Buildup of gold nanoparticle multilayer thin films based on the covalent-bonding
      interaction between boronic acids and polyols.
AB  - A novel method for the fabrication of gold nanoparticle multilayer films based on
      the covalent-bonding interaction between boronic acid and polyols, poly(vinyl
      alcohol) (PVA), was developed. The multilayer buildup was monitored by UV-vis
      absorbance spectroscopy, which showed a linear increase of the film absorbance
      with the number of adsorbed Au layers and indicated the stepwise and uniform
      assembling process. The atomic force microscopy (AFM) image showed that a compact
      gold multilayer thin film was successfully assembled. The residual boronic acid
      group on the surface of thin film could incorporate glycosylated-protein
      horseradish peroxidase (HRP), and good catalytic activity for H2O2 could be
      observed.

PMID- 16413031
TI  - Buffy coat preparation is a convenient source of progenitors for culturing mature
      human mast cells.
AB  - Mast cells are unique immune cells that release a spectrum of chemical mediators
      contributing to the inflammatory symptoms of allergic disorders. Mature mast
      cells have recently been cultured from CD34(+) progenitors isolated from fresh
      umbilical cord blood and adult peripheral blood. In the current study, we
      investigated whether buffy coat preparations, which are readily available from
      blood banks, could be used as a convenient and more abundant source of
      progenitors for culturing human mast cells. We were able to culture a homogeneous
      population of human mast cells from progenitor cells isolated from human buffy
      coat. Morphologically, our cultured mast cells contained abundant cytoplasmic
      granules which stained positively using antibodies against human mast cell
      tryptase and, to a lesser extent, with those against human mast cell chymase.
      Functionally, these cultured mast cells responded to anti-human-IgE by releasing
      histamine in a dose-dependent manner after sensitization with human IgE. Taken
      together, buffy coat preparations can be a convenient source for culturing human
      mast cells which are predominantly tryptase positive only and express functional
      high-affinity IgE receptors.

PMID- 16413032
TI  - A simple method for unbiased quantitation of adoptively transferred cells in
      solid tissues.
AB  - In a mouse model, we demonstrate how to obtain a direct, unbiased estimate of the
      total number of adoptively transferred cells in a variety of organs at different
      time points. The estimate is obtained by a straightforward method based on the
      optical fractionator principle. Specifically, non-stimulated C57BL/6J mouse
      splenocytes were labelled with carboxyfluorescein diacetate succinimidyl ester
      (CFSE) and adoptively transferred to normal C57BL/6J mice by intravenous
      injection. The total number of CFSE-positive cells was subsequently determined in
      lung, spleen, liver, kidney, and inguinal lymph node at six different time points
      following adoptive transfer (from 60 s to 1 week), providing a quantitative
      estimate of the organ distribution of the transferred cells over time. These
      estimates were obtained by microscopy of uniform samples of thick sections from
      the respective organs. Importantly, the samples were chosen and prepared in
      accordance with the optical fractionator principle. We demonstrate that the
      method is simple, precise, and well suited for quantitative immunological
      studies.

PMID- 16413033
TI  - Model for RNA binding and the catalytic site of the RNase Kid of the bacterial
      parD toxin-antitoxin system.
AB  - The toxin Kid and antitoxin Kis are encoded by the parD operon of Escherichia
      coli plasmid R1. Kid and its chromosomal homologues MazF and ChpBK have been
      shown to inhibit protein synthesis in cell extracts and to act as ribosome
      independent endoribonucleases in vitro. Kid cleaves RNA preferentially at the 5'
      side of the A residue in the nucleotide sequence 5'-UA(A/C)-3' of single-stranded
      regions. Here, we show that RNA cleavage by Kid yields two fragments with a 2':3'
      cyclic phosphate group and a free 5'-OH group, respectively. The cleavage
      mechanism is similar to that of RNases A and T1, involving the uracil 2'-OH
      group. Via NMR titration studies with an uncleavable RNA mimic, we demonstrate
      that residues of both monomers of the Kid dimer together form a concatenated RNA
      binding surface. Docking calculations based on the NMR chemical shifts, the
      cleavage mechanism and previously reported mutagenesis data provide a detailed
      picture of the position of the AUACA fragment within the binding pocket. We
      propose that residues D75, R73 and H17 form the active site of the Kid toxin,
      where D75 and R73 are the catalytic base and acid, respectively. The RNA sequence
      specificity is defined by residues T46, S47, A55, F57, T69, V71 and R73. Our data
      show the importance of these residues for Kid function, and the implications of
      our results for related toxins, such as MazF, CcdB and RelE, are discussed.

PMID- 16413035
TI  - Mathematical model for the estimation of hemodynamic and oxygenation variables by
      tissue spectroscopy.
AB  - This article presents a quasistatic, compartmental model of tissue-level
      hemodynamics and oxygenation that leads to a set of formulas, which is suitable
      to calculate important physiological variables from the mean tissue concentration
      and saturation of hemoglobin, measured by tissue spectroscopy. Dimensioned
      quantities are represented relative to their baseline value in the equations
      (relative value = perturbed/baseline). All model parameters are non-dimensional.
      The model is based and extends on a number of previous works: previous models of
      similar aim and scope are consolidated, and every critical assumptions and
      approximations are treated explicitly; extensions include for example the
      incorporation of the Fahraeus-effect and the separate estimation of the volume
      changes of the arterial and the venous compartments. The information content of
      spectroscopic data alone is shown to be valuable, but limited: the relative
      venous volume, the oxygen extraction fraction and the relative cellulovascular
      coupling (defined as the ratio of blood flow and oxygen consumption) can be
      calculated from these data, if the alterations in arterial blood volume are
      negligible. The number of variables estimated by the derived formulas can be
      increased if local blood flow is measured simultaneously: in this case, the
      relative arterial and venous volume and resistance, the oxygen extraction
      fraction, and the relative oxygen consumption can be determined. Given that this
      model considers arterial blood pressure, saturation and hematocrit as its inputs,
      when measured, the model becomes applicable in such conditions as hyper- or
      hypotension, hypoxic hypoxia, hemodilution and hemorrhage, where these variables
      do change. The estimation of the changes in arterial resistance can be applied to
      estimate the extent of an autoregulatory response.

PMID- 16413036
TI  - Acute and chronic electroconvulsive shock in rats: effects on peripheral markers
      of neuronal injury and glial activity.
AB  - Electroconvulsive therapy is considered one of the most effective treatments of
      major depression, but controversy still exists on whether it may be brain
      damaging. The aim of this work was to evaluate the cerebrospinal fluid (CSF)
      levels of neuron specific enolase (NSE), protein S100B and lactate of rats
      submitted to acute and chronic models of ECS. Rats were submitted to either one
      shock (acute) or a series of eight shocks, applied one at every 48 h (chronic).
      CSF samples were collected at 0, 3, 6, 12, 24, 48 and 72 h after the shock in the
      acute model and at these same time intervals after the last shock in the chronic
      model. Both models did not produce significant alterations in the levels of NSE.
      S100B levels were significantly increased at 6 h in the chronic model (p<0.0001).
      There was a significant increase in the levels of lactate at 0 h in both models
      (p<0.001). These results support the proposition that ECS does not produce neural
      damage, and suggest that the alterations in the levels of S100B and lactate may
      reflect an astrocytic activity of a protective nature.

PMID- 16413037
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) suppresses IL-6-induced STAT3
      phosphorylation via electrophilic reactivity in endothelial cells.
AB  - In this study, the effects of 15d-PGJ(2) were investigated in IL-6-activated
      endothelial cells (ECs). 15d-PGJ(2) was found to abrogate phosphorylation on
      tyr705 of STAT3 in IL-6-treated ECs, in a dose- and time-dependent manner, but
      did not inhibit serine phosphorylation of STAT3 and the upperstream JAK2
      phosphorylation. Other PPAR activators, such as WY1643 or ciglitazone, had no
      effect upon IL-6-induced STAT3 phosphorylation. Additionally, neither
      orthovanadate nor l-NAME treatment reverses the inhibition of STAT3
      phosphorylation by 15d-PGJ(2). Otherwise, the effect of 15d-PGJ(2) requires the
      alpha,beta-unsaturated carbonyl group in the cyclopentane ring. A 15d-PGJ(2)
      analog, 9,10-Dihydro-15d-PGJ(2), which lack alpha,beta-unsaturated carbonyl group
      showed no increase in ROS production and no effect in inhibition of IL-6-induced
      STAT3 phosphorylation. The electrophilic compound, acrolein, mimics the
      inhibition effect of 15d-PGJ(2). Among the antioxidants, only NAC and glutathione
      reversed the effects of 15d-PGJ(2). NAC, glutathione and DTT all reversed the
      inhibition of STAT3 phosphorylation when preincubated with 15d-PGJ(2). The
      inhibition of ICAM-1 gene expression by 15d-PGJ(2) was abrogated by NAC and
      glutathione in IL-6-treated ECs. Taken together, these results suggest that 15d
      PGJ(2) inhibits IL-6-stimulated phosphorylation on tyr705 of STAT3 dependent on
      its own electrophilic reactivity in ECs.

PMID- 16413034
TI  - Free energy landscapes of RNA/RNA complexes: with applications to snRNA complexes
      in spliceosomes.
AB  - We develop a statistical mechanical model for RNA/RNA complexes with both
      intramolecular and intermolecular interactions. As an application of the model,
      we compute the free energy landscapes, which give the full distribution for all
      the possible conformations, for U4/U6 and U2/U6 in major spliceosome and
      U4atac/U6atac and U12/U6atac in minor spliceosome. Different snRNA experiments
      found contrasting structures, our free energy landscape theory shows why these
      structures emerge and how they compete with each other. For yeast U2/U6, the
      model predicts that the two distinct experimental structures, the four-helix
      junction structure and the helix Ib-containing structure, can actually coexist
      and specifically compete with each other. In addition, the energy landscapes
      suggest possible mechanisms for the conformational switches in splicing. For
      instance, our calculation shows that coaxial stacking is essential for
      stabilizing the four-helix junction in yeast U2/U6. Therefore, inhibition of the
      coaxial stacking possibly by protein-binding may activate the conformational
      switch from the four-helix junction to the helix Ib-containing structure.
      Moreover, the change of the energy landscape shape gives information about the
      conformational changes. We find multiple (native-like and misfolded)
      intermediates formed through base-pairing rearrangements in snRNA complexes. For
      example, the unfolding of the U2/U6 undergoes a transition to a misfolded state
      which is functional, while in the unfolding of U12/U6atac, the functional helix
      Ib is found to be the last one to unfold and is thus the most stable structural
      component. Furthermore, the energy landscape gives the stabilities of all the
      possible (functional) intermediates and such information is directly related to
      splicing efficiency.

PMID- 16413039
TI  - Gender differences in ischemia-reperfusion-induced microcirculatory and
      epithelial dysfunctions in the small intestine.
AB  - Female sex hormones have been reported to preserve endothelial integrity and to
      reduce inflammation. However, gender-related differences in the intestinal
      mucosal barrier function during compromised perfusion after ischemia and
      transplantation have not been defined. Herein, we applied intravital microscopy
      to determine the mucosal epithelial and intestinal microcirculatory responses in
      ileal villus and longitudinal muscle layers in a murine model of 30-min
      intestinal ischemia and 90-min reperfusion. In male animals, the entire
      reperfusion period was characterized by a significantly increased epithelial
      permeability. This was associated with an early leukocytic inflammatory response
      and late alterations in functional capillary density, capillary red blood cell
      velocity and mitochondrial redox state. In contrast, the female intestine
      exhibited a delayed increase in epithelial permeability during postischemic
      reperfusion. This was associated with a late leukocytic inflammatory response
      which did not affect the microcirculatory function. Nonetheless, at the end of
      the 90-min reperfusion period, the neutrophilic infiltration and structural
      mucosal disintegration in the female intestine were found to be pronounced to a
      similar extent as in the male intestine. These results suggest that in small
      intestinal ischemia-reperfusion the leukocytic inflammatory response and
      microcirculatory dysfunction develop more rapidly and are initially more
      pronounced in males, but the hormonal status in females is not capable of
      preventing the final manifestations of reperfusion injury.

PMID- 16413038
TI  - Preferential radiation sensitization of prostate cancer in nude mice by
      nutraceutical antioxidant gamma-tocotrienol.
AB  - Gamma-tocotrienol (GT) is a member of the vitamin E family. Our preliminary
      studies indicated that it protected mice from lethal irradiation, so we
      hypothesized that GT might be a radiation sensitizing agent for tumors. To test
      this, we induced prostate tumors by injecting PC3 cells into nude BALB/c mice.
      When the tumors were about 5 mm in diameter, mice were injected subcutaneously
      with 400 mg/kg gamma-tocotrienol and irradiated 24 h later at the site of the
      tumor with a dose of 12 Gy (60)Cobalt. Tumor size was monitored for 24 days after
      radiation. Tumor tissues as well as normal tissues like rectum, kidney, and liver
      were monitored for lipid peroxidation on day 4 and day 24 after radiation. The
      results indicated that the size of the tumors was reduced by almost 40%, but only
      in GT-treated and irradiated mice. In unstimulated and Fe-stimulated lipid
      peroxidation groups, lipid peroxidation in the tumors from irradiated mice
      increased to 135% and 150%, respectively, four days after irradiation and 33% and
      66% in the same groups, respectively, 24 days after irradiation. In general,
      lipid peroxidation in the rectum did not increase in GT-treated and irradiated
      mice, although there was a slight increase in Fe-stimulated lipid peroxidation
      (29%) four days after irradiation. Unexpectedly, the kidneys were as equally
      sensitized to lipid peroxidation as the tumors. Liver tissue was protected in the
      short-term from radiation-induced lipid peroxidation. These studies indicate that
      the radiotherapy efficacy of prostate cancer can be increased with GT and a pro
      oxidant if the kidneys can be shielded.

PMID- 16413040
TI  - Ecological quality status of coastal benthic ecosystems in the Sea of Marmara.
AB  - The macrofauna in the north Marmara Sea were identified and evaluated with
      univariate measures and biotic indices (BENTIX, AMBI). As expected, the diversity
      and species' variety decreased as the sediments became muddier and as the stress
      increased. The AMBI index failed to detect the spatial differentiation of the
      EcoQ between the sites whereas, the BENTIX index succeeded (in 70% of the cases)
      in producing an ecologically relevant classification reflecting the environmental
      pressures. Results suggested that risks of reduced species' richness and
      diversity from organic loading and other associated stressors in sediments should
      be relatively low at TOC concentrations < about 6 mg/g, high at
      concentrations>about 22 mg/g, and intermediate at concentrations in-between. It
      is suggested that these TOC critical points may be used as a general screening
      level indicator for assessing the EcoQ in association with reduced biodiversity
      over coastal areas receiving organic wastes and other pollutants from human
      activities. It is further suggested that both assignment of species to ecological
      groups and classification scales for biotic indices (AMBI, BENTIX) for sites in
      the Mediterranean Sea should be readjusted so as to be closer related to
      environmental variables.

PMID- 16413041
TI  - Cellular radiation effects and the bystander response.
AB  - This report reviews briefly some of the findings reported over the past 2 years
      that enhance our understanding of the radiation-induced bystander effect. These
      developments include: technicological advances; the role of oxidative stress; the
      effect of cytoplasmic irradiation; cell-to-cell communication; and evidence that
      Connexin 43 mediated intercellular communication is induced by radiation
      exposure. A few overriding unanswered questions are discussed. These include:
      what is the signal(s) transmitted from irradiated to bystander cells; what is the
      relationship between the bystander response and other non-targeted effects of
      radiation; are there beneficial effects associated with the bystander response;
      and what is the significance of the bystander effect for radiation protection?

PMID- 16413043
TI  - Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species
      specificity, is partly immune-mediated.
AB  - The human coronavirus HCoV-OC43 causes a significant fraction of upper
      respiratory tract infections. Most coronaviruses show a strong species
      specificity, although the SARS-Coronavirus crossed species from palm civet cats
      to infect humans. Similarly, HCoV-OC43, likely a member of the same coronavirus
      group as SARS-CoV, readily crossed the species barrier as evidenced by its rapid
      adaptation to the murine brain [McIntosh, K., Becker, W.B., Chanock, R.M., 1967.
      Growth in suckling-mouse brain of "IBV-like" viruses from patients with upper
      respiratory tract disease. Proc Natl Acad Sci U.S.A. 58, 2268-73]. Herein, we
      investigated two consequences of this plasticity in species tropism. First, we
      showed that HCoV-OC43 was able to infect cells from a large number of mammalian
      species. Second, we showed that virus that was passed exclusively in suckling
      mouse brains was highly virulent and caused a uniformly fatal encephalitis in
      adult mice. The surface glycoprotein is a major virulence factor in most
      coronavirus infections. We identified three changes in the HCoV-OC43 surface
      glycoprotein that correlated with enhanced neurovirulence in mice; these were
      located in the domain of the protein responsible for binding to host cells. These
      data suggest that some coronaviruses, including HCoV-OC43 and SARS-CoV, readily
      adapt to growth in cells from heterologous species. This adaptability has
      facilitated the isolation of HCoV-OC43 viral variants with markedly differing
      abilities to infect animals and tissue culture cells.

PMID- 16413045
TI  - Feeding behavior, diet, and the functional consequences of jaw form in
      orangutans, with implications for the evolution of Pongo.
AB  - Orangutans are amongst the most craniometrically variable of the extant great
      apes, yet there has been no attempt to explicitly link this morphological
      variation with observed differences in behavioral ecology. This study explores
      the relationship between feeding behavior, diet, and mandibular morphology in
      orangutans. All orangutans prefer ripe, pulpy fruit when available. However, some
      populations of Bornean orangutans (Pongo pygmaeus morio and P. p. wurmbii) rely
      more heavily on bark and relatively tough vegetation during periods of low fruit
      yield than do Sumatran orangutans (Pongo abelii). I tested the hypothesis that
      Bornean orangutans exhibit structural features of the mandible that provide
      greater load resistance abilities to masticatory and incisal forces. Compared to
      P. abelii, P. p. morio exhibits greater load resistance abilities as reflected in
      a relatively deeper mandibular corpus, deeper and wider mandibular symphysis, and
      relatively greater condylar area. P. p. wurmbii exhibits most of these same
      morphologies, and in all comparisons is either comparable in jaw proportions to
      P. p. morio, or intermediate between P. p. morio and P. abelii. These data
      indicate that P. p. morio and P. p. wurmbii are better suited to resisting large
      and/or frequent jaw loads than P. abelii. Using these results, I evaluated
      mandibular morphology in P. p. pygmaeus, a Bornean orangutan population whose
      behavioral ecology is poorly known. Pongo p. pygmaeus generally exhibits
      relatively greater load resistance capabilities than P. abelii, but less than P.
      p. morio. These results suggest that P. p. pygmaeus may consume greater amounts
      of tougher and/or more obdurate foods than P. abelii, and that consumption of
      such foods may intensify amongst Bornean orangutan populations. Finally, data
      from this study are used to evaluate variation in craniomandibular morphology in
      Khoratpithecus piriyai, possibly the earliest relative of Pongo from the late
      Miocene of Thailand, and the late Pleistocene Hoa Binh subfossil orangutan
      recovered from Vietnam. With the exception of a relatively thicker M(3)
      mandibular corpus, K. piriyai has jaw proportions that would be expected for an
      extant orangutan of comparable jaw size. Likewise, the Hoa Binh subfossil does
      not differ in skull proportions from extant Pongo, independent of the effects of
      increase in jaw size. These results indicate that differences in skull and
      mandibular proportions between these fossil and subfossil orangutans and extant
      Pongo are allometric. Furthermore, the ability of K. piriyai to resist jaw loads
      appears to have been comparable to that of extant orangutans. However, the
      similarity in jaw proportions between P. abelii and K. piriyai suggest the latter
      may have been dietarily more similar to Sumatran orangutans.

PMID- 16413042
TI  - Isolation and characterisation of a Salvia bogotensis seed lectin specific for
      the Tn antigen.
AB  - A lectin was isolated and characterised from Salvia bogotensis seeds. Removal of
      the abundant pigments and polysaccharides, which are present in seeds, was an
      essential step in its purification. Several procedures were assayed and the best
      suited, including Pectinex treatment, DEAE-cellulose and affinity chromatography,
      led to a protein being obtained amounting to 18-20mg/100g seeds having high
      specific agglutination activity (SAA). The lectin specifically agglutinated human
      Tn erythrocytes and was inhibited by 37mM GalNAc, 0.019mM ovine submaxillary
      mucin (OSM) or 0.008mM asialo bovine submaxillary mucin (aBSM). Enzyme-linked
      lectinosorbent assay (ELLSA) revealed strong binding to aOSM and aBSM,
      corroborating Tn specificity, whereas no binding to fetuin or asialo fetuin was
      observed. The lectin's monomer MW (38,702Da), amino acid composition, pI,
      carbohydrate content, deglycosylated form MW, thermal stability and Ca(2+) and
      Mn(2+) requirements were determined. Evidence of the existence of two glycoforms
      was obtained. The lectin's specificity and high affinity for the Tn antigen,
      commonly found in tumour cells, makes this protein a useful tool for
      immunohistochemical and cellular studies.

PMID- 16413044
TI  - Impact of polymorphisms in the DC-SIGNR neck domain on the interaction with
      pathogens.
AB  - The lectins DC-SIGN and DC-SIGNR augment infection by human immunodeficiency
      virus (HIV), Ebolavirus (EBOV) and other pathogens. The neck domain of these
      proteins drives multimerization, which is believed to be required for efficient
      recognition of multivalent ligands. The neck domain of DC-SIGN consists of seven
      sequence repeats with rare variations. In contrast, the DC-SIGNR neck domain is
      polymorphic and, in addition to the wild type (wt) allele with seven repeat
      units, allelic forms with five and six sequence repeats are frequently found. A
      potential association of the DC-SIGNR genotype and risk of HIV-1 infection is
      currently under debate. Therefore, we investigated if DC-SIGNR alleles with five
      and six repeat units exhibit defects in pathogen capture. Here, we show that wt
      DC-SIGNR and patient derived alleles with five and six repeats bind viral
      glycoproteins, augment viral infection and tetramerize with comparable
      efficiency. Moreover, coexpression of wt DC-SIGNR and alleles with five repeats
      did not decrease the interaction with pathogens compared to expression of each
      allele alone, suggesting that potential formation of hetero-oligomers does not
      appreciably reduce pathogen binding, at least under conditions of high
      expression. Thus, our results do not provide evidence for diminished pathogen
      capture by DC-SIGNR alleles with five and six repeat units. Albeit, we cannot
      exclude that subtle, but in vivo relevant differences remained undetected, our
      analysis suggests that indirect mechanisms could account for the association of
      polymorphisms in the DC-SIGNR neck region with reduced risk of HIV-1 infection.

PMID- 16413047
TI  - Free-ranging European bisons accumulate more cadmium in the liver and kidneys
      than domestic cattle in north-eastern Poland.
AB  - It has been shown that free-ranging big game animals accumulate several-fold more
      cadmium (Cd) in the liver and kidneys than domestic animals. To examine possible
      reasons for this difference, in the present work we determined the concentrations
      of Cd in the liver and kidney cortex of European bisons (n=23) from Bialowieza
      Forest (north-eastern Poland) and domestic cattle (n=15) from the same region; in
      addition, analyses of Cd in the grasses and soil as well as of soil pH were
      carried out. The accumulation of Cd in liver and kidney cortex of the female
      bisons correlated significantly with the age up to 7 years, but stabilized
      thereafter. The 7-12-year-old bisons had 2.14- and 2.25-fold higher
      concentrations of Cd in the liver and kidney cortex, respectively, than the age
      matched domestic cattle. Notably, the Cd levels in the liver and kidneys of the 8
      12-year-old cattle were comparable to those found in the 2-year-old and 4-6-year
      old bisons, respectively. The content of Cd in the grasses from Bialowieza Forest
      appeared to be 2.1-fold higher than that in the plants from the pastures.
      Similarly, the concentration of water-extractable Cd in the soil was 2.7-fold
      greater in Bialowieza Forest than in the pastures, despite the fact that nitric
      acid-extractable Cd (total Cd) was similar in the soils from the two sites. The
      concentration of water-extractable Cd in the soil as well as the content of Cd in
      the grasses inversely correlated with soil pH, which appeared to be significantly
      lower in Bialowieza Forest. These data indicate that soil pH is probably
      responsible for the higher concentrations of Cd in the feed and tissues of bisons
      as compared with those of domestic cattle.

PMID- 16413046
TI  - Effects of aging on Ca2+ signaling in murine mesenteric arterial smooth muscle
      cells.
AB  - Pathophysiological changes in arterial smooth muscle structure and function occur
      with aging and there are a number of reports illustrating reductions in vascular
      responsiveness with aging. While much is known about arterial remodeling and
      functional adaptations with aging, very little is known about the biophysical
      adaptations in individual arterial myocytes. Cytosolic Ca2+ signaling, involving
      activation of L-type Ca2+ channels on the plasma membrane as well as InsP3 and
      ryanodine receptors on the sarcoplasmic reticulum, is integral to vascular tone
      and reactivity. Thus, we tested the hypothesis that aging results in reductions
      in the functional expression of L-type channels and temporal aspects of ryanodine
      receptor and InsP3 receptor Ca2+ signaling, in mesenteric arterial smooth muscle
      cells isolated from 6 and 30 months old C57Bl/6 mice. Comparisons of L-type
      current activity were made using dialyzed, whole-cell voltage-clamp techniques
      and Ba2+ as charge carrier. Ca2+ signaling was measured using fura-2 fluorescence
      microscopy techniques. Cell morphological changes were also investigated using
      electrophysiological and immunocytochemical approaches. The amplitudes of L-type
      Ca2+ currents were increased in older mice, but this was associated with membrane
      surface area increases of approximately 50%, due to increases in cell length not
      cell width. Consequently, L-type Ca2+ current densities were preserved with age,
      indicating functional channel expression was unchanged. In contrast, aging was
      associated with decrements in Ca2+ signaling in response to either ryanodine
      receptor stimulation by caffeine or InsP3 receptor activation with phenylephrine.
      These changes with aging may be related to the previously reported depression in
      myogenic reactivity.

PMID- 16413048
TI  - The effect of age on clinical/pathologic features, surgical morbidity, and
      outcome in patients with endometrial cancer.
AB  - OBJECTIVE: To evaluate the effect of age on clinical/pathologic features,
      surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All
      women with surgically treated endometrial cancer at the University of Washington
      in Seattle, Washington between January 1990 and January 2000 were eligible; 396
      patients underwent retrospective chart review. Statistical analysis was performed
      by SPSS. Median follow-up time was 33 months (range, 1 to 120 months). RESULTS:
      Age was < 45 years in 15% of patients, between 46 and 64 years in 47% of
      patients, and > 65 years in 38% of patients. Younger patients were statistically
      more obese than older patients (Body Mass Index of 40.3 kg/m2 vs. 35.3 kg/m2 vs.
      31.0 kg/m2, P < 0.001). Intraoperatively, there were no differences between the
      three groups in the percentage of patients with lymph node sampling, operative
      time, blood loss, or complications. Postoperatively, older patients had more
      wound infections (P = 0.002), more cardiac events (P = 0.001), and more episodes
      of ileus (P = 0.025). Evaluation of pathology revealed that patients < 45 years
      old were statistically more likely to have endometrioid histology, grade I
      tumors, and stage IA disease. Women over age 65 were significantly more likely to
      have papillary serous histology, grade 3 tumors, and stage IC as compared to the
      younger patients. A subset analysis of patients > 75 years of age showed an
      increase in the percentage of patients with papillary serous histology (22% vs.
      3%, P = 0.055), grade 3 disease (42% vs. 16%, P < 0.001), and stage IC disease
      (21% vs. 3%, P = 0.001) when compared to patients < 45 years old. Evaluation of
      endometrioid tumors only revealed a similar pattern of deeper myometrial invasion
      and higher tumor grade as age increased. CONCLUSIONS: Younger patients with
      endometrial cancer are generally more obese, with lower grade, lower stage
      disease, and with more favorable histologic cell types. Despite this,
      approximately a quarter have stage II-IV disease and 9% have positive lymph
      nodes. The older patients represent a dramatically different subset of patients.
      They are more likely to have aggressive papillary serous histology, higher grade
      tumors, and advanced stage disease. Age should be a consideration in appropriate
      referrals to gynecologic oncologists.

PMID- 16413049
TI  - Connectivity among semantic associates: an fMRI study of semantic priming.
AB  - Semantic priming refers to a reduction in the reaction time to identify or make a
      judgment about a stimulus that has been immediately preceded by a semantically
      related word or picture and is thought to result from a partial overlap in the
      semantic associates of the two words. A semantic priming lexical decision task
      using spoken words was presented in event-related fMRI and behavioral paradigms.
      Word pairs varied in terms of semantic relatedness and the connectivity between
      associates. Thirteen right-handed subjects underwent fMRI imaging and 10
      additional subjects were tested in a behavioral version of the semantic priming
      task. It was hypothesized priming would be greatest, reaction time fastest, and
      cortical activation reduced the most for related word pairs of high connectivity,
      followed by related word pairs of low connectivity, and then by unrelated word
      pairs. Behavioral and fMRI results confirmed these predictions. fMRI activity
      located primarily in bilateral posterior superior and middle temporal regions
      showed modulation by connectivity and relatedness. The results suggest that these
      regions are involved in semantic processing.

PMID- 16413050
TI  - Bioaccumulation of PCB congeners in marine benthic infauna.
AB  - Field concentrations of polychlorinated biphenyls (PCBs) were measured in
      sediment and nine marine soft bottom invertebrate species. Lipid- and organic
      carbon normalised biota-sediment accumulation factors (BSAFs) were determined for
      29 nonplanar and 11 coplanar congeners. To investigate whether the
      bioaccumulation was in thermodynamic equilibrium with the sediment, the
      determined BSAFs were compared to theoretically calculated ones to obtain a
      BSAFdet./BSAFtheor-ratio. Large interspecific variations were found: one
      suspension feeding and one deposit feeding species of brittle stars (Amphiura
      filiformis and A. chiajei), and one predatory polychaete (Glycera rouxii) had
      ratios>1 for congeners with logKow>6.5. In these species there was also a linear
      relationship between logKow and BSAF, both for coplanar and for planar congeners
      but with lower values for coplanar ones. For other species the pattern was more
      scattered. Only the deposit feeding polychaete Melinna cristata had
      BSAFdet./BSAFtheor-ratios<1 for all congeners. Thus, the interspecific variations
      in bioaccumulation did not correlate with differences in feeding strategies, but
      may be caused by differences in biotransformation, and in age and size of the
      analysed specimens.

PMID- 16413051
TI  - How an ill-conceived methodological approach can condemn the medical use of ozone
      therapy.

PMID- 16413052
TI  - Osteoinductive porous titanium implants: effect of sodium removal by dilute HCl
      treatment.
AB  - In a previous study, we observed that chemically and thermally treated plasma
      sprayed porous titanium possesses intrinsic osteoinductivity and that bone
      formation occurs after 12 months in the muscles of beagle dogs. The aim of this
      study was to optimize the surface treatment and to accelerate the
      osteoinductivity. Previous studies have reported that sodium removal converts the
      sodium titanate layer on the surface of an alkali-treated titanium plate into a
      more bioactive titania layer. In this study, we developed a dilute hydrochloric
      acid (HCl) treatment for porous titanium, which removed sodium from the complexly
      shaped porous structure more effectively than conventional hot water treatment.
      Three types of surface treatments were applied: (a) alkali and heat treatment (AH
      treatment); (b) alkali, hot water, and heat treatment (Water-AH treatment); and
      (c) alkali, dilute HCl, hot water, and heat treatment (HCl-AH treatment). The
      osteoinductivity of the materials implanted in the back muscles of adult beagle
      dogs was examined at 3, 6, and 12 months. The HCl-AH-treated porous bioactive
      titanium implant had the highest osteoinductivity, with induction of a large
      amount of bone formation within 3 months. The dilute HCl treatment was considered
      to give both chemical (titania formation and sodium removal) and topographic
      (etching) effects on the titanium surface, although we cannot determine which is
      the predominant factor. Nevertheless, adding the dilute HCl treatment to the
      conventional chemical and thermal treatments is a promising candidate for
      advanced surface treatment of porous titanium implants.

PMID- 16413053
TI  - In vitro effects of Ag+ on planktonic and adhered cells of fluconazole-resistant
      and susceptible strains of Candida albicans, C. glabrata and C. krusei.
AB  - Planktonic and attached cells of strains of Candida albicans, C. glabrata and C.
      krusei with varied susceptibilities to fluconazole (FCZ) were compared for their
      relative susceptibilities to Ag+ via cell recovery and flow cytometric analyses.
      All strains lost membrane permeability and were non-recoverable upon culture
      after 1h exposure in morpholino-ethanesulfonic acid (MES) buffer fortified with
      <or= 2.0 microg/ml Ag+. Cells attached to silicone over a 2-h period demonstrated
      enhanced tolerance to FCZ and to a lesser degree to Ag+. Minimal inhibitory
      concentrations of Ag+ in defined media increased in the order C. glabrata, C.
      krusei, C. albicans. Susceptibilities to Ag+ did not correlate with tolerance or
      resistance to FCZ.

PMID- 16413054
TI  - Bone formation enhanced by implanted octacalcium phosphate involving conversion
      into Ca-deficient hydroxyapatite.
AB  - The present study was designed to investigate whether hydrolysis of synthetic
      octacalcium phosphate (OCP) into hydroxyapatite affects bone formation. Mouse
      bone marrow stromal ST-2 cells and primary calvarial osteoblastic cells were
      cultured on the dishes pre-coated with OCP or its hydrolyzed Ca-deficient
      hydroxyapatite (OCP hydrolyzate; HL). The capacity of proliferation and
      differentiation was determined up to day 20. Granules of OCP and HL were
      implanted into critical-size rat calvaria defects for 4 and 12 weeks, and then
      bone formation was measured by histomorphometry. Structural changes of incubated
      and implanted OCP were determined by X-ray diffraction (XRD) and Fourier
      transform infrared spectroscopy (FTIR). The proliferation of both ST-2 and
      primary osteoblasts cultured on OCP or HL was initially inhibited, whereas their
      differentiation to osteoblasts was promoted at last. Implantation of OCP in bone
      defect more significantly enhanced bone formation than that of HL until 12 weeks.
      OCP tended to convert to apatite in vitro and in vivo. The conversion of the
      implanted OCP was ascertained to advance gradually with implantation periods.
      Taken together, these results suggest that OCP supports appositional bone
      formation and OCP-apatite conversion may be involved in this stimulatory capacity
      of OCP.

PMID- 16413055
TI  - Release of calcitonin gene-related peptide from the isolated mouse heart:
      methodological validation of a new model.
AB  - Calcitonin gene-related peptide (CGRP), a potent vasodilator released from a
      subset of sensory Adelta- and C-fiber afferents, has been suggested to play a
      beneficial role in myocardial ischemia. Variations in CGRP release can possibly
      be correlated with diseases that involve changes in activity or degeneration of
      cardial afferent fibers. The aim of the present study was to evaluate a simple
      and easily reproducible model for measuring stimulated CGRP release from cardial
      afferents. For this reason freshly isolated mouse hearts were passed through
      incubations in series of 25 min. Solutions consisting of oxygenated synthetic
      interstitial fluid. Dissolved substances such as capsaicin, bradykinin and
      potassium chloride were used as excitatory test stimuli. For comparison, isolated
      mouse hearts were perfused with the same solutions through a cannula inserted
      into the rising aorta. The eluates were processed using an enzyme immuno-assay
      for measurement of CGRP concentrations. Capsaicin, bradykinin and the potassium
      solution caused concentration-dependent increases in CGRP release. There were no
      differences in CGRP release when oxygen was replaced by nitrogen in the
      solutions. Immersion of hearts caused significantly more CGRP release than
      perfusion with same solutions. The results suggest that mouse heart immersion is
      more effective than coronary perfusion in measuring stimulated CGRP release from
      cardial afferents which are widely distributed in the epicardium but rare in
      deeper myocardial layers. The results are discussed with respect to the
      potentially important vasodilatory and cardioprotective functions of CGRP
      released from activated epicardial afferents.

PMID- 16413057
TI  - Misconceived bioethics?: The misconception of the "therapeutic misconception".
AB  - Bioethics needs to include study of the social and historical context in which
      ethical meanings in medical encounters make sense. It needs to do this in order
      to remain relevant, vibrant, and aware of how it might unwittingly facilitate the
      agendas of others. As an illustration, this paper critiques some of the accepted
      meanings and purposes of the idea of the Therapeutic Misconception (TM) which has
      been an increasingly attractive concept with which to organize thinking about
      experimentation ethics. By considering the history of alternative viewpoints
      against which TM was offered as a replacement, this paper suggests that TM, and
      bioethics more generally, may contribute to increasingly technocratic and
      standardized practices in medicine.

PMID- 16413056
TI  - Phase II trial of subcutaneous recombinant human interleukin 11 with subcutaneous
      recombinant human granulocyte-macrophage colony stimulating factor in patients
      with acute myeloid leukemia (AML) receiving high-dose cytarabine during
      induction: ECOG 3997.
AB  - Randomized trials of substituting high-dose cytarabine (HiDAC) for standard dose
      cytarabine (SDAC) during induction therapy for newly diagnosed AML have not
      demonstrated an improvement in the complete remission (CR) rate. Phase II trials
      of the scheduled administration of HiDAC after SDAC suggest an improved outcome.
      The hematological complications of intensification are considerable. GM-CSF after
      chemotherapy improved the survival of older patients in a randomized trial.
      Recombinant human interleukin 11, a thrombopoietic cytokine, reduced the
      incidence of chemotherapy-induced thrombocytopenia in patients with solid tumors.
      Therefore, 34 patients were treated, with newly diagnosed AML less than 56 years
      of age, with daunorubicin 45 mg/m2 on days 1-3, cytarabine 100mg/m2 days 1-7 and
      cytarabine 2g/m2 for 12 h on days 8-10 (7+3+3). rhIL-11 (50 microg/kg/day,) and
      GM-CSF (250 microg/kg/day) were administered subcutaneously from day 11 until
      recovery. The complete remission rate was 59% (90% C.I. 43-73%). The median time
      to recovery of neutrophils to >500 and platelets to > or =20,000 microl(-1) was
      27 days (95% C.I. 27-30 days) and 25 days (95% C.I. 24-29 days), respectively.
      The trial does not confirm the high CR rate observed in phase II trials, despite
      optimal supportive care.

PMID- 16413058
TI  - Detection of serum neopterin for early assessment of dengue virus infection.
AB  - OBJECTIVE: Neopterin is generated and released in increased amounts by
      macrophages upon activation by interferon-gamma during Th1-type immune response.
      The potential usefulness of neopterin in early prognostic information of dengue
      virus infection was investigated. METHODS: Neopterin concentrations were
      determined in serum samples from 110 dengue fever (DF) patients. The neopterin
      levels were compared with those in 50 measles and 40 influenza patients; 155
      healthy blood donors served as controls. RESULTS: In acute sera of DF patients
      mean neopterin concentration was 48.2 nmol/L, which was higher than that in
      patients with measles (mean: 36.3 nmol/L) and influenza (18.8 nmol/L) and in
      healthy controls (6.7 nmol/L; P<0.001). In the patients with confirmed DF, an
      early neopterin elevation was detected already at the first day after the onset
      of symptoms and rose to a maximum level of 54.3 nmol/L 4 days after the onset.
      Higher increase of neopterin level in DF patients was associated with longer
      duration of fever and thus predicted the clinical course of the disease.
      CONCLUSIONS: Neopterin concentrations were found significantly higher in DF
      patients compared with healthy controls and also with other viral infections
      (P<0.001) and may allow early assessment of the severity of DF.

PMID- 16413059
TI  - First recurrent infection with vancomycin-resistant enterococcus from Turkey.
AB  - Here we describe a case of a neuroblastoma patient with recurrent vancomycin
      resistant enterococcal infection successfully treated with ciprofloxacin. This is
      the first case of recurrent vancomycin-resistant enterococcal infection in our
      hospital and Turkey.

PMID- 16413060
TI  - Method for urinary neopterin measurements by HPLC.
AB  - In the June 2004 issue of the Journal, Drs. Ribeiro de Castro and coworkers
      described a new method to determine neopterin concentrations in urine by HPLC and
      UV-absorption detection [de Castro MR, Di Marco GS, Arita DY, Teixeira LC,
      Pereira AB, Casarini DE. Urinary neopterin quantification by reverse-phase high
      performance liquid chromatography with ultraviolet detection. J Biochem Biophys
      Methods 2004;59:275-83 ]. Although simple and rapid, unfortunately this report
      does not consider any possible analytical complications known from the
      biochemistry of neopterin. The major problem with this method is that the authors
      did not at all consider possible interferences with related compounds.

PMID- 16413061
TI  - Reduced apoptosis in sheep ileal Peyer's patch is associated with low levels of
      follicle centre carbonic anhydrase reactivity.
AB  - Apoptosis in lymphoid follicles of the ileal Peyer's patch (IPP) in 21 sheep of
      two different age groups was visualized by the TdT-mediated dUTP nick end
      labelling (TUNEL) method, and quantified using computer-assisted image analysis.
      The IPP follicle carbonic anhydrase (CA) reactivity was evaluated in the same
      samples. No significant differences with respect to apoptosis and CA reactivity
      were found between sheep aged 5 and 11 months. Individual variation in apoptotic
      activity correlated with the follicle centre CA reactivity. The group of animals
      found to have predominantly atypical ileal lymphoid follicles (more than 80% of
      total number of follicles) with features resembling jejunal Peyer's patch
      follicles, had lower number of apoptotic cells and reduced CA reactivity compared
      to the rest of the animals. The differences in CA reactivity in the follicle
      centres probably represent a variation in the presence of CA rich approximately
      50 nm membrane-bounded particles known to be a feature of the sheep IPP. The
      present results suggest that the particles are involved in the modulation of the
      lymphocyte proliferation of the IPP follicles.

PMID- 16413062
TI  - B7-1 and B7-2: similar costimulatory ligands with different biochemical,
      oligomeric and signaling properties.
AB  - B7-1 and B7-2 are homologous costimulatory ligands expressed on the surface of
      antigen presenting cells (APCs). Binding of these molecules to the T cell
      costimulatory receptors, CD28 and CTLA-4, is essential for the activation and
      regulation of T cell immunity. Despite strong structural similarities, B7-1 and
      B7-2 exhibit different biochemical features, and their binding to the
      costimulatory receptors results in distinct T cell functional outcomes. Using
      photobleaching based fluorescence resonance energy transfer (FRET), our previous
      studies have demonstrated that B7-1 and B7-2 have different cell surface
      oligomeric states. While B7-1 is present as a dimer, B7-2 exists as a monomer on
      the cell surface suggesting that the unique cell surface oligomeric states of the
      costimulatory ligands may play a key role in the regulation of T cell responses.
      Moreover, signaling via B7-1 and B7-2 in dendritic cells has been reported to be
      dependent on their simultaneous expression, raising the possibility that their
      direct interaction or their involvement in synergistic signaling pathways may
      play a role in the function of antigen presenting cells. We discuss physiological
      relevance of distinct oligomeric states of B7-1 and B7-2 and address whether
      these molecules can associate with one another on the cell surface to form hetero
      oligomers. Our findings suggest that B7-1 and B7-2 do not form hetero-oligomers,
      underscoring the biological relevance of dimeric and monomeric state of B7-1 and
      B7-2, respectively.

PMID- 16413063
TI  - IL-12 driven upregulation of P-selectin ligand on myelin-specific T cells is a
      critical step in an animal model of autoimmune demyelination.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating
      disease of the central nervous system. IL-12p40 monokines play a critical role in
      the generation of EAE-inducing CD4+T cells. Here we show that IL-12 directly
      upregulates the expression of the adhesion molecule, P-selectin glycoprotein
      ligand (PSGL-1), on B10.PL MBP-TCR transgenic T cells during their initial
      encounter with antigen. Pre-incubation of IL-12-stimulated myelin-reactive CD4+T
      cells with a blocking antibody against PSGL-1 reduced the incidence and severity
      of EAE. We conclude that IL-12-driven PSGL-1 expression can facilitate the
      development of autoimmune demyelination.

PMID- 16413064
TI  - Relapse of methamphetamine-seeking behavior in C57BL/6J mice demonstrated by a
      reinstatement procedure involving intravenous self-administration.
AB  - There is an urgent need to develop a reliable mouse model of relapse to address
      the genetic factors involved in susceptibility to relapse of drug-seeking
      behavior by using mutant mice. This paper presents a feasible way to reinstate
      extinguished methamphetamine (METH)-seeking behavior. Male C57BL/6J mice acquired
      stable nose-poking responses for taking METH after approximately 10 daily 3-h
      sessions of METH (0.1mg/kg/infusion) self-administration under a fixed ratio 1 or
      2 (FR1/2) schedule. During the self-administration, cue- and hole-lamps indicated
      the availability of METH and were inactivated simultaneously with each infusion
      for 5s. The mice were exposed to extinction training in the absence of METH
      paired stimuli (cue- and hole-lamps) and METH infusion, until they met the
      extinction criterion (less than 25 active responses or 30% of active responses in
      the stable self-administration phase on 2 consecutive days). METH-paired stimuli
      (cue- and hole-lamps) during METH self-administration reliably triggered a
      relapse of METH-seeking behavior in the absence of METH infusion. A combination
      of non-contingent intravenous (i.v.) priming and self-injected METH also
      increased the reinstatement of METH-seeking behavior in the absence of METH
      paired stimuli (cue- and hole-lamps) and without METH infusion posterior to the
      self-injection. These results suggest that the mouse model of relapse in our
      study might provide a new stage for the exploration of genetic factors involved
      in relapse of drug dependence and of the underlying mechanisms of drugs of abuse.

PMID- 16413065
TI  - Corticotropin-releasing factor neurons in the hypothalamic paraventricular
      nucleus are involved in arousal/yawning response of rats.
AB  - Our previous studies have suggested that activation of the hypothalamic
      paraventricular (PVN) descending oxytocinergic projections is involved in the
      induction of yawning accompanied by an arousal response, but the possibility that
      neural systems other than the oxytocinergic system in the PVN also mediate the
      arousal/yawning response cannot be ruled out. We assessed the activity of
      corticotropin-releasing factor (CRF) neurons during yawning induced by the PVN
      stimulation in anesthetized, spontaneously breathing rats using double-staining
      for c-Fos and CRF. Yawning response was evaluated by monitoring an intercostals
      electromyogram as an index of inspiratory activity and a digastric electromyogram
      as an indicator of mouth opening. We also recorded the electrocorticogram (ECoG)
      to determine the arousal response during yawning. Microinjection of l-glutamate
      (2-5 nmol) into the PVN produced a frequent yawning accompanied by an arousal
      shift in the ECoG, and these behavioral effects were associated with a
      significant increase of c-Fos positive CRF neurons in the medial parvocellular
      subdivision of the PVN. In addition, a marked enhancement in the c-Fos expression
      was found in the both locus coeruleus (LC) and global area in the cortex when the
      frequency of yawning response was increased by the PVN stimulation, suggesting
      that the arousal response during yawning might be mediated by the activation of
      LC neurons. The present study suggests that an activation of CRF neurons in the
      PVN is responsible for the arousal response accompanied by yawning behavior.

PMID- 16413066
TI  - Neurotoxic lesions of the dorsal and ventral hippocampus impair acquisition and
      expression of trace-conditioned fear-potentiated startle in rats.
AB  - Pavlovian delay conditioning, in which a conditioned stimulus (CS) and
      unconditioned stimulus (US) co-terminate, is thought to reflect non-declarative
      memory. In contrast, trace conditioning, in which the CS and US are temporally
      separate, is thought to reflect declarative memory. Hippocampal lesions impair
      acquisition and expression of trace conditioning measured by the conditioned
      freezing and eyeblink responses, while having little effect on the acquisition of
      delay conditioning. Recent evidence suggests that lesions of the ventral
      hippocampus (VH) impair conditioned fear under conditions in which dorsal
      hippocampal (DH) lesions have little effect. In the present study, we examined
      the time-course of fear expression after delay and trace conditioning using the
      fear-potentiated startle (FPS) reflex, and the effects of pre- and post-training
      lesions to the VH and DH on trace-conditioned FPS. We found that both delay- and
      trace-conditioned rats displayed significant FPS near the end of the CS relative
      to the unpaired control group. In contrast, trace-conditioned rats displayed
      significant FPS throughout the duration of the trace interval, whereas FPS
      decayed rapidly to baseline after CS offset in delay-conditioned rats. In
      experiment 2, both DH and VH lesions were found to significantly reduce the
      overall magnitude of FPS compared to the control group, however, no differences
      were found between the DH and VH groups. These findings support a role for both
      the DH and VH in trace fear conditioning, and suggest that the greater effect of
      VH lesions on conditioned fear might be specific to certain measures of fear.

PMID- 16413067
TI  - A behavioural characterization of neonatal infection-facilitated memory
      impairment in adult rats.
AB  - We have reported that exposure to bacteria (Escherichia coli) during the neonatal
      period in rats is associated with impaired memory for a novel context in
      adulthood. However, impairment is only observed if a peripheral immune challenge
      (bacterial lipopolysaccharide (LPS)) is administered immediately following
      context exposure. The goal of the current study was to more fully characterize
      this phenomenon. In Experiment 1, memory impairment as a result of neonatal
      infection and subsequent LPS challenge was observed in juvenile rats, indicating
      that the changes induced by infection occur early on and are then manifest
      throughout the lifespan. In Experiment 2, infection in juvenile rats did not lead
      to LPS-induced memory impairment in adulthood, suggesting there is a critical
      period for early infection-induced alterations. In Experiments 3 and 4, memory
      for a novel context was impaired in neonatally infected rats, a task that is
      dependent on the hippocampus, whereas cued memory for a tone, which does not
      depend on the hippocampus, was not impaired. Furthermore, long-term, but not
      short-term contextual memory was impaired in adult rats infected as neonates
      following an LPS challenge either 24 h before or immediately after conditioning.
      Finally, in Experiment 5, no neonatal group differences were observed in
      corticosterone or open field behaviour, suggesting that decreased freezing to a
      conditioned context reflects impaired memory, and not simply hyperactivity or
      altered stress reactivity. Taken together, we have demonstrated that neonatal
      infection results in robust hippocampal-dependent memory impairment following an
      immune challenge in adulthood using a number of conditioning paradigms.

PMID- 16413068
TI  - Genotype differences in behavior and tyrosine hydroxylase expression between wild
      type and progesterone receptor knockout mice.
AB  - Progesterone receptor (PR) activation can modulate the expression of male sexual
      behavior, both acutely in adulthood as well as during development, through long
      lasting effects on neural differentiation. One mechanism by which PR activation
      may affect behavior, during either epoch of life, is through alterations of the
      dopaminergic system. We investigated the effects of PR deletion on the
      sensitivity of sexual behavior to dopamine antagonism in male wild-type (WT) and
      progesterone receptor knockout (PRKO) mice and found that WT mice were more
      behaviorally sensitive to the effects of dopamine D1 receptor blockade. There
      were also genotype differences in tyrosine hydroxylase-immunoreactivity (TH-ir)
      in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA)
      as well as genotype differences in how TH expression changed in response to
      social and sexual experience. In particular, in the VTA, sexually experienced
      PRKO mice had significantly more cells expressing TH than sexually experienced WT
      mice. In the SNc, experienced PRKO males had significantly more cells expressing
      TH than naive PRKO males. Thus, it appears that PR deletion affects the display
      of sexual behavior and its modulation by dopamine, as well as the differentiation
      of dopaminergic cells and the plasticity of those cells in response to social
      environment and behavioral experience.

PMID- 16413069
TI  - Modulation by cADPr of Ca2+ mobilization and oxidative response in
      dimethylsulfoxide- or retinoic acid-differentiated HL-60 cells.
AB  - In human phagocytic cells, reactive oxygen species (ROS) generation in response
      to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLF) is largely dependent on
      cytosolic free calcium concentration ([Ca2+]i). Cyclic ADP-ribose (cADPr) is able
      to regulate Ca2+ release from intracellular stores through the ryanodine receptor
      but its potential role in biological responses has so far not been determined. In
      this study, we examined whether extracellular and intracellular cADPr is required
      in fMLF-induced [Ca2+]i rise and consequently in the oxidative response in human
      neutrophil-like HL-60 cells differentiated with dimethylsulfoxide or all-trans
      retinoic acid (ATRA). We establish that extracellular cADPr cannot elicit [Ca2+]i
      elevation. Furthermore, we demonstrate that 8-Br-cADPr, a functional antagonist
      of cADPr, inhibits Ca2+ entry into HL-60 cells differentiated with ATRA and
      stimulated with fMLF (95+/-4 and 148+/-5 nM respectively, n=3). Finally, we show
      that this partial inhibition of Ca2+ mobilization is unrelated to ROS production
      (10.0+/-0.3 vs. 9.6+/-0.5 A.U., n=3). In conclusion, we showed that cADPr can
      control fMLF-induced Ca2+ influx but is unable to regulate a Ca2+-dependent
      biological response, i.e. H2O2 production.

PMID- 16413070
TI  - Cell internalization and traffic pathway of Clostridium botulinum type C
      neurotoxin in HT-29 cells.
AB  - The bacterium Clostridium botulinum type C produces a progenitor toxin (C16S
      toxin) that binds to O-linked sugar chains terminating with sialic acid on the
      surface of HT-29 cells prior to internalization [A. Nishikawa, N. Uotsu, H.
      Arimitsu, J.C. Lee, Y. Miura, Y. Fujinaga, H. Nakada, T. Watanabe, T. Ohyama, Y.
      Sakano, K. Oguma, Biochem. Biophys. Res. Commun. 319 (2004) 327-333] [21]. Based
      on this, it was hypothesized that the C16S toxin is internalized via clathrin
      coated pits. To examine this possibility, the internalized toxin was observed
      with a fluorescent antibody using confocal laser-scanning microscopy. The
      confocal images clearly indicated that the C16S toxin was internalized mainly via
      clathrin-coated pits and localized in early endosomes. The toxin was colocalized
      with caveolin-1 which is one of the components of caveolae, however, implying the
      toxin was also internalized via caveolae. The confocal images also showed that
      the neurotoxin transported to the endosome was transferred to the Golgi
      apparatus. However, the non-toxic components were not merged with the Golgi
      marker protein, TGN38, implying the neurotoxin was dissociated from progenitor
      toxin in endosomes. These results suggested that the C16S toxin was separated to
      the neurotoxin and other proteins in endosome and the neurotoxin was further
      transferred to the Golgi apparatus which is the center for protein sorting.

PMID- 16413074
TI  - Inferior myocardial infarction and extensive atherosclerosis in a patient with
      double right coronary artery.

PMID- 16413073
TI  - ST segment elevation and new right bundle branch block: broadening the
      differential diagnosis.

PMID- 16413072
TI  - A case of multivessel coronary artery spasm resulting in wandering ST segment
      elevation.
AB  - We describe a case of recurrent episodes of resting myocardial ischaemia
      associated with ST elevation on ECG in different territories. Multivessel
      coronary artery spasm was demonstrated that was reversed with intracoronary
      glycerine trinitrate.

PMID- 16413076
TI  - Endocannabinoid-mediated short-term suppression of excitatory synaptic
      transmission to medium spiny neurons in the striatum.
AB  - Medium spiny neurons in the dorsal striatum receive glutamatergic excitatory
      synaptic inputs from the cerebral cortex. These synapses undergo long-term
      depression that requires release of endocannabinoids from medium spiny neurons
      and activation of cannabinoid CB1 receptors. However, it remains unclear how
      cortico-striatal synapses exhibit endocannabinoid-mediated short-term
      suppression, which has been found in various brain regions including the
      hippocampus and cerebellum. Endocannabinoids are released from postsynaptic
      neurons by strong depolarization and resultant Ca2+ elevation or activation of
      postsynaptic Gq/11-coupled receptors such as group I metabotropic glutamate
      receptors (mGluRs) and M1/M3 muscarinic acetylcholine receptors. Moreover,
      endocannabioids are effectively released when weak depolarization is combined
      with Gq/11-coupled receptor activation. We found that muscarinic activation
      induced transient suppression of excitatory synaptic transmission to medium spiny
      neurons, which was independent of retrograde endocannabinoid signaling but was
      mediated directly by presynaptic muscarinic receptors. Neither postsynaptic
      depolarization alone nor depolarization and muscarinic activation caused
      suppression of cortico-striatal synapses. In contrast, activation of group I
      mGluRs readily suppressed cortico-striatal excitatory synaptic transmission.
      Furthermore, postsynaptic depolarization induced clear suppression when combined
      with group I mGluR activation. These results indicate that group I mGluRs but not
      muscarinic receptors contribute to endocannabinoid-mediated short-term
      suppression of cortico-striatal excitatory synaptic transmission.

PMID- 16413071
TI  - Mutation of Thr466 in SHP2 abolishes its phosphatase activity, but provides a new
      substrate-trapping mutant.
AB  - Most classical phosphotyrosyl phosphatases (PTPs), including the Src homology
      phosphotyrosyl phosphatase 2 (SHP2) possess a Thr or a Ser residue immediately C
      terminal to the invariant Arg in the active site consensus motif (H/V-C-X5-R
      S/T), also known as the "signature motif". SHP2 has a Thr (Thr466) at this
      position, but its importance in catalysis has not been investigated. By employing
      site-directed mutagenesis, phosphatase assays and substrate-trapping studies, we
      demonstrate that Thr466 is critical for the catalytic activity of SHP2. Its
      mutation to Ala abolishes phosphatase activity, but provides a new substrate
      trapping mutant. We further show that the nucleophilic Cys459 is not involved in
      substrate trapping by Thr466Ala-SHP2 (T/A-SHP2). Mutation of Thr466 does not
      cause significant structural changes in the active site as revealed by the
      trapping of the epidermal growth factor receptor (EGFR), the physiological
      substrate of SHP2, and by orthovanadate competition experiments. Based on these
      results and previous other works, we propose that the role of Thr466 in the
      catalytic process of SHP2 could be stabilizing the sulfhydryl group of Cys459 in
      its reduced state, a state that enables nucleophilic attack on the phosphate
      moiety of the substrate. The T/A-SHP2 harbors a single mutation and specifically
      interacts with the EGFR. Since the nucleophilic Cys459 and the proton donor
      Asp425 are intact in the T/A-SAHP2, it offers an excellent starting material for
      solving the structure of SHP2 in complex with its physiological substrate.

PMID- 16413075
TI  - Echocardiographic anatomy of ascending aorta dilatation: correlations with aortic
      valve morphology and function.
AB  - BACKGROUND: Different anatomical forms of proximal aortic dilations associated
      with aortic valve disease can be distinguished by echocardiography. Differences
      in the anatomy could reflect different pathogeneses and need for different
      therapeutic approaches. The present study assessed the clinical features
      associated to each anatomical form, particularly focusing on the relations with
      valve morphology and function. METHODS: Trans-thoracic and trans-esophageal
      echocardiography reports of 552 adult patients (mean age 60.4+/-12.8 years; 379
      male) with mild to severe proximal aorta dilation were reviewed. The
      relationships between the anatomy of aorta dilatation (distinguished into "root
      type" dilatation, with maximal enlargement at the sinuses, and "mid-ascending
      type", with maximal diameter at the mid-ascending tract) and aortic valve
      morphology (tricuspid/bicuspid) and function (normal/stenosis/regurgitation) were
      assessed. The relations with other clinico-echocardiographic variables were also
      tested in univariate and multivariate analysis. RESULTS: A "root type" dilatation
      was found in 4.9% tricuspid patients with stenosis, 32.3% with regurgitation,
      22.5% with normal valve function (p=0.018). Dilatation prevailed at the mid
      ascending tract in patients with bicuspid aortic valve, irrespective of valve
      function (stenotic: 92.9%, regurgitant: 87.9%, normal: 94.3%; p=0.23).
      Predominant root involvement was significantly more prevalent in male patients
      (24.8% versus 5.2% in females; p<0.001). In multivariate analysis, predominant
      aortic valve regurgitation (OR=1.83; p=0.028) independently predicted root site,
      while predominant aortic valve stenosis (OR=3.70; p=0.001), bicuspidity (OR=2.90;
      p=0.005) and female sex (OR=6.10; p<0.001) predicted mid-ascending site.
      CONCLUSIONS: Pathogenetical considerations arise from the evidence of
      preferential mid-ascending localization of bicuspid-associated aortic
      dilatations. This finding is consistent with previous studies on bicuspid valve
      models revealing a wall stress overload beyond the sino-tubular ridge.

PMID- 16413077
TI  - Microbiological and chemical changes during the fermentation of African locust
      bean (Parkia biglobosa) to produce afitin, iru and sonru, three traditional
      condiments produced in Benin.
AB  - African locust bean (Parkia biglobosa) was processed to produce afitin, iru and
      sonru, three different types of condiment from Benin. Whereas the fermentation of
      African locust bean to produce afitin is carried out for 24 h without using any
      additive, the fermentation for iru and sonru production takes place for 48 h with
      adding respectively "iku-iru" and "yanyanku" two traditional malvacene bean-based
      (Hibiscus sabdariffa) additives. The main microorganisms involved in the
      fermentation of the three condiments were Bacillus spp., although Staphylococcus
      spp. was found in lower number. The use of additive seems to enhance the initial
      Bacillus counts in iru and sonru, but also a slightly higher Staphylococcus count
      was observed. The number of staphylococci did not exceed 10(2) cfu/g and it was
      below the detection level at the end of the fermentation (24 h) in afitin; it
      reached a level of about 10(6) cfu/g at 12-18 h in iru and sonru followed by a
      decrease to about 5 x 10(4) cfu/g after 48 h of fermentation. The final pH and
      total basic volatile nitrogen content of iru and sonru are higher than those of
      afitin. Proximate composition changes are similar in both fermenting iru and
      sonru, but different in afitin, the latter showing a slight decrease of proteins
      of about 5% whereas for iru and sonru they increased to about 6%. Ash, crude fat
      and fibre contents also increased during the fermentation in the three products
      whereas total carbohydrates decreased significantly. Due to their long
      fermentation time, iru and sonru are very soft products as they are preferred by
      some consumers whereas afitin is preferred with cotyledons having less soft
      texture.

PMID- 16413078
TI  - Water immiscible ionic liquids as solvents for whole cell biocatalysis.
AB  - Whole cell biocatalysis can effectively be used for the production of
      enantiomerically pure compounds, but efficiency is often low. Toxicity and poor
      solubility of substrates and products are the main obstacles. In this study,
      water immiscible ionic liquids are shown to have no damaging effects on the cell
      membranes of Escherichia coli and Saccharomyces cerevisiae. Thus, they can be
      used as biocompatible solvents for microbial biotransformations exemplified by an
      increase in yield of chiral alcohol synthesis. As key point to the success of
      these processes, the distribution ratio of the reactants between the ionic liquid
      and the aqueous phase was identified. The use of ionic liquids as substrate
      reservoir and in situ extracting agent for the asymmetric reduction of various
      ketones resulted in an increase of chemical yield from <50% to 80-90% in simple
      batch processes. (R)-1-(4-chlorophenyl)ethanol was produced at a higher initial
      reaction rate in the biphasic system (>50 microM s(-1) L(-1)) compared to the
      aqueous system. This result demonstrates that good mass transfer rates can be
      obtained despite the relatively high viscosity of ionic liquids.

PMID- 16413079
TI  - Gene silencing through RNA interference (RNAi) in vivo: strategies based on the
      direct application of siRNAs.
AB  - RNA interference (RNAi) offers great potential not only for in vitro target
      validation, but also as a novel therapeutic strategy based on the highly specific
      and efficient silencing of a target gene, e.g. in tumor therapy. Since it relies
      on small interfering RNAs (siRNAs), which are the mediators of RNAi-induced
      specific mRNA degradation, a major issue is the delivery of therapeutically
      active siRNAs into the target tissue/target cells in vivo. For safety reasons,
      strategies based on (viral) vector delivery may be of only limited clinical use.
      The more desirable approach is to directly apply catalytically active siRNAs.
      This review highlights the recent knowledge on the guidelines for the selection
      of siRNAs which show high activity in the absence of non-specific siRNA effects.
      It then focuses on approaches to directly use siRNA molecules in vivo and gives a
      comprehensive overview of in vivo studies based on the direct application of
      siRNAs to induce RNAi. One promising approach is the in vivo siRNA delivery
      through complexation of chemically unmodified siRNAs with polyethylenimine (PEI).
      The anti-tumoral effects of PEI/siRNA-based targeting of tumor-relevant genes in
      vivo are described.

PMID- 16413082
TI  - An adaptive signal compression system with pre-specified reconstruction quality
      and compression rate.
AB  - Two essential properties of a signal compression method are the compression rate
      and the distance between the original signal and the reconstruction from the
      compressed signal. These two properties are used to assess the performance and
      quality of the method. In a recent work [B. Tumer, B. Demiroz, Lecture Notes in
      Computer Science-Computer and Information Sciences, volume 2869, chapter Signal
      Compression Using Growing Cell Structures: A Transformational Approach, Springer
      Verlag, 2003, pp. 952-959], an adaptive signal compression system (ACS) is
      presented which defines the performance of the system as a function of the system
      complexity, system sensitivity and data size. For a compression method, it is
      desirable to formulate the performance of the system as a function of the system
      complexity and sensitivity to optimize the performance of the system. It would be
      further desirable to express the reconstruction quality in terms of the same
      system parameters so as to know up front what compression rate to end up with for
      a specific reconstruction quality. In this work, we modify ACS such that the
      modified ACS (MACS) estimates the reconstruction quality for a given system
      complexity and sensitivity. Once this relation is identified it is possible to
      optimize either compression rate or reconstruction quality with respect to system
      sensitivity and system complexity while limiting the other one.

PMID- 16413083
TI  - DtiStudio: resource program for diffusion tensor computation and fiber bundle
      tracking.
AB  - A versatile resource program was developed for diffusion tensor image (DTI)
      computation and fiber tracking. The software can read data formats from a variety
      of MR scanners. Tensor calculation is performed by solving an over-determined
      linear equation system using least square fitting. Various types of map data,
      such as tensor elements, eigenvalues, eigenvectors, diffusion anisotropy,
      diffusion constants, and color-coded orientations can be calculated. The results
      are visualized interactively in orthogonal views and in three-dimensional mode.
      Three-dimensional tract reconstruction is based on the Fiber Assignment by
      Continuous Tracking (FACT) algorithm and a brute-force reconstruction approach.
      To improve the time and memory efficiency, a rapid algorithm to perform the FACT
      is adopted. An index matrix for the fiber data is introduced to facilitate
      various types of fiber bundles selection based on approaches employing multiple
      regions of interest (ROIs). The program is developed using C++ and OpenGL on a
      Windows platform.

PMID- 16413084
TI  - Targeting colloidal particulates to thoracic lymph nodes.
AB  - BACKGROUND: Thoracic lymphatics and lymph nodes can be affected by cancer and
      other diseases. Micro- or nanoparticulates are used as carriers for therapeutic
      agents. We investigated the lymphatic distribution after intrapleural
      administration of three different particulates. METHODS: Various micro- and
      nanoparticles of charcoal, polystyrene and poly(lactide-co-glycolide) were
      administered into the pleural space of rats to study the lymphatic distribution
      of particles from the pleural cavity to the thoracic lymph nodes. Experimental
      animal models included healthy rats, rats following pneumonectomy and rats
      bearing orthotopic lung cancer to mimic relevant clinical scenarios and
      pathophysiology. Macroscopic examination, light microscopy, fluorescence
      microscopy complemented by transmission electron microscopy analysis of the
      lymphatic tissue allowed precise mapping and detection of the particulates in the
      thoracic lymphatic system. RESULTS: We found that (1) the particles studied are
      cleared by the regional thoracic lymphatic system when placed in the pleural
      space; (2) the lymphatic uptake occurred as early as 3h after injection and is
      primarily through the parietal pleura; (3) the transport of particles to regional
      lymph nodes was consistently found in all three animal models; (4) particles of
      0.7-2 microm in size give the best lymphatic distribution. CONCLUSIONS: Regional
      thoracic lymphatics and lymph nodes can be accessed by colloidal particles
      injected into the pleural space.

PMID- 16413081
TI  - Transdermal delivery of aminoglycosides: amikacin transport and iontophoretic non
      invasive monitoring.
AB  - The aim of this paper was to try to single out new administration strategies for
      aminoglycoside antibiotics. The objectives of the work were to reduce the
      systemic absorption in the case of topical application and to achieve plasma
      levels within the therapeutic window in case of systemic administration. Amikacin
      (AK) was chosen as a model aminoglycoside, as it has a broad spectrum of activity
      against Gram-negative bacteria. Additionally, since the therapeutic use of
      aminoglycosides requires careful monitoring, the feasibility of noninvasive
      monitoring of AK by reverse iontophoresis was explored in preliminary
      experiments. Permeation experiments were performed in vitro using rabbit ear skin
      as barrier. From the results obtained, it can be concluded that topical delivery
      of amikacin is possible for the treatment of local diseases, both using a
      commercial gel formulation and an innovative transdermal film, the latter being
      able to reduce in a significant way the risks of systemic absorption. When anodal
      iontophoresis at pH 4.0 was applied, amikacin transport and, to a limited extent,
      accumulation were increased. Reverse iontophoresis gave promising results, since
      AK could be extracted across the skin at the cathode, and this can be taken as a
      reference point to develop and optimize the technique.

PMID- 16413080
TI  - Purification and characterization of recombinant human interleukin-29 expressed
      in Escherichia coli.
AB  - Human interleukin (IL)-29 is the latest member of the class II cytokine family.
      However, as a result of lacking efficient method to generate relatively large
      quantity of IL-29, little is known of its functions in man. In the present study,
      an Escherichia coli expression system for the rapid expression of the human IL-29
      gene was developed. It involved of cloning IL-29 gene into the pET-44 Ek/LIC
      vector, which allowed expression of IL-29 with a fusion tag consisting of the
      NusA protein, polyhistidine and S peptide (Nus-His-S-tag), and introducing a
      thrombin recognition site between the fusion tag and IL-29. The expressed fusion
      protein was purified by S-protein agarose affinity chromatography, and the fusion
      tag was removed from recombinant IL-29 by cleavage with thrombin. The purified IL
      29 appeared a single band on SDS-PAGE, and the yield of IL-29 was 60 mg from 1 l
      of bacterial culture. N-terminal sequencing confirmed the identity of the
      purified protein. The recombinant IL-29 showed specific antiviral activity that
      was comparable to the commercially available IFN alfa-2b preparation.

PMID- 16413085
TI  - Tuberculosis in stem cell transplant patients.
AB  - Tuberculosis (TB) is an increasing health problem, and patients undergoing stem
      cell transplantation (SCT) are at high risk of acquiring TB. Following a review
      of the medical literature, this article reports the current situation of TB in
      SCT patients. A PubMed search was undertaken using the keywords 'tuberculosis',
      'stem cell transplantation' and 'bone marrow transplantation', and cases with
      meaningful data for analysis were included. The medical literature contains
      relatively few data on TB and SCT. Although there is a risk of TB in allogeneic
      SCT patients, this is less than in solid organ transplant patients, and the risk
      in autologous SCT patients is similar to the risk in the general population. The
      incidence of TB in SCT patients is proportional to the incidence of TB in the
      general population. Evidence favouring TB prophylaxis is not well established.
      While allogeneic transplantation carries a risk of TB, this is not true for
      autologous transplantation. Prophylaxis can only be an option for selected
      patients or countries with high rates of TB.

PMID- 16413086
TI  - The crustacean hyperglycemic hormones from an euryhaline crab Pachygrapsus
      marmoratus and a fresh water crab Potamon ibericum: eyestalk and pericardial
      isoforms.
AB  - The structures of crustacean hyperglycemic hormones (CHH) were investigated in
      two crabs, the coastal euryhaline crab Pachygrapsus marmoratus and the fresh
      water crab Potamon ibericum. The neuropeptide mRNAs were extracted from
      pericardial and X-organs (PO and XO), and the sequences of the cDNA encoding the
      hormones' precursors were determined. The X-organ preprohormones are composed of
      29 and 28 amino acid signal peptides in P. marmoratus and P. ibericum
      respectively, followed by 43 and 41 amino acid crustacean hyperglycemic hormone
      precursor related peptide (CPRP) flanking the 72 amino acid crustacean
      hyperglycemic hormones. A similar organization is reported for pericardial
      preprohormones with identical sequences for the signal peptide, the CPRP and the
      N-terminal sequences of CHH (1-40), but remaining sequences (41-72 and 41-71)
      differing considerably. In P. marmoratus two CHH cDNAs were characterized from XO
      and evidences were obtained for the existence of at least two forms in the PO.
      From our results and by comparison with other known sequences, a consensus
      pattern for crab pericardial CHH could be pointed out. Analysis of the data
      presented in this article using phylogenetic methods reveals that the two crab
      species studied are much closer than previously predicted.

PMID- 16413088
TI  - The effect of emissions of fertilizer production on the environment contamination
      by cadmium and arsenic in southern Brazil.
AB  - The distribution of cadmium and arsenic in rainwater, surface soil and
      groundwater in a zone of influence of emissions of a phosphate fertilizer factory
      has been investigated. The analysis of rainwater along a wind line shows that
      cadmium in the soluble form precipitates close to emission source, whereas
      arsenic migrates further and also in the soluble form precipitates at a greater
      distance. The pH controls the distribution of cadmium and arsenic in rain and
      groundwater. Concentration of soluble cadmium along the impact line increases
      with reduction of pH and arsenic, contrary to the increase of pH. Concentrations
      of cadmium and arsenic in surface soil correlate well among themselves near to
      emission point. In a zone of confluence of emissions with sea air at a distance
      from the factory there is sedimentation of arsenic on a geochemical barrier and
      formation of a separate anomaly in soil.

PMID- 16413087
TI  - Elevated levels of inducible heat shock 70 proteins in human brain.
AB  - Differential expression of heat shock genes can modulate protein folding and
      stress-related cell death. There have been no comparisons of their levels of
      expression in animals and humans. Levels of expression of heat shock 70 genes in
      human brain were compared to levels in non-stressed and heat-stressed brain of
      rat. Levels of hsp70 proteins in human brain were 43-fold higher than in non
      stressed rat brain and 14-fold higher than highest induced levels in brains of
      heat-shocked rats. Levels of constitutively synthesized hsc70 proteins were
      approximately 1.5-fold higher in human than in rat. Higher levels of hsp70
      proteins in human brain may serve to protect brain cells against stress-related
      death or dysfunction throughout the lifespan.

PMID- 16413090
TI  - The veterinary antibiotic oxytetracycline and Cu influence functional diversity
      of the soil microbial community.
AB  - There are increasing concerns over the effects of veterinary antibiotics and
      heavy metals in agricultural soils. The widely used veterinary antibiotic
      oxytetracycline (OTC), Cu and their combination on soil microbial community
      function were assessed with the Biolog method. The microbial community was
      extracted from the soil and exposed to a 0.85% sodium chloride solution
      containing OTC (0, 1, 5, 11, 43, 109 and 217 microM), or Cu (0, 10, 20, 100 and
      300 microM), or combination of the two pollutants (OTC 0, 5, 11 microM and Cu 0,
      20 microM). Functional diversity, evenness, average well color development (AWCD)
      and substrate utilization decreased significantly with increasing concentrations
      of OTC or Cu (p < 0.005). The critical concentrations were 11 microM for OTC and
      20 microM for Cu. The combination of OTC and Cu significantly decreased Shannon's
      diversity, evenness and utilization of carbohydrates and carboxylic acids
      compared to individual one of the contaminants. The antibiotic OTC and Cu had
      significant negative effects on soil microbial community function, particularly
      when both pollutants were present.

PMID- 16413091
TI  - Source determination of highly chlorinated biphenyl isomers in pine needles -
      comparison to several PCB preparations.
AB  - The isomer specific composition of 13 technical PCB formulations of different
      origin and of pine needles was analyzed using GC/MS and HRGC/HRMS.
      Nonachlorinated biphenyls were identified in 11 among 13 formulations analyzed,
      with the highest abundance found for highly chlorinated ones (Aroclors 1268 and
      1260, Chlorofen, Sovol, Kanechlors 600 and 500, Delor 106, Clophen A60).
      Decachlorobiphenyl was identified only in Aroclor 1268, Clophen A60, Aroclor 1260
      and Chlorofen, comprising, respectively, 8.9, 2.8, 1.3 and 0.82% of the total
      bulk of nona- and decaCBs detected. Nona- and decaCB were detected in pine
      needles in Poland with the highest concentrations found at the sites neighboring
      to a former production sites of the Polish PCB formulations, while in pine
      needles collected around the Tokyo Bay nona- and decacCB were detected only in
      four of 10 sites and the concentrations corresponded to those found at the rural
      areas of Poland.

PMID- 16413092
TI  - The geography of self-injury: spatial patterns in attempted and completed
      suicide.
AB  - This study uses hospital discharge data, death certificates and medical examiner
      data for New Jersey for 1999-2001 to investigate whether fatal and non-fatal self
      injury exhibit similar geographic patterns. Findings show that the demographic
      characteristics of individuals committing fatal and non-fatal self-injury are
      quite different. Furthermore, attempted and completed suicides have a somewhat
      different geographical pattern. Municipality-level determinants of suicide and
      non-fatal self-injury were estimated in two separate models. While measures of
      isolation such as low population density and high proportions of households with
      only one member were predictive of completed suicides, non-fatal self-injury was
      related to unemployment and median age. Both types of self-injury were more
      common in municipalities which lost population between 1990 and 2000, and where
      divorce rates were high. Population-based suicide prevention efforts should be
      aided by the knowledge that although there are some similarities in the spatial
      pattern of completed and attempted suicides, there are some important differences
      in significant determinants.

PMID- 16413089
TI  - Effects of eutrophication on vitellogenin gene expression in male fathead minnows
      (Pimephales promelas) exposed to 17alpha-ethynylestradiol in field mesocosms.
AB  - This study evaluated the effect of aquatic secondary nutrient supply levels
      (nitrogen and phosphorus) on the subcellular response of adult male fathead
      minnows (Pimephales promelas) exposed to a single nominal concentration of
      17alpha-ethynylestradiol (EE2), a potent synthetic estrogen, under quasi-natural
      field conditions. Outdoor mesocosms were maintained under low, medium, and high
      nutrient supply conditions as categorized by total phosphorus (TP) level (nominal
      0.012, 0.025, and 0.045 mg TP/L, respectively), and treated with EE2 with and
      without a carrier solvent. Using reverse transcription-polymerase chain reaction
      methods, vitellogenin gene (Vg) expression was determined in the fish collected
      at 0 h, 8 h, 24 h, 4 d, 7 d, and 14 d post-exposure. Induction of Vg was detected
      as early as 8h post-exposure, with and without the carrier solvent, and persisted
      through Day 14. Results showed Vg to be significantly greater at low nutrient
      levels (p<0.05), suggesting that EE2 bioavailability to the fish was likely
      greater under less-turbid water conditions.

PMID- 16413093
TI  - Beyond paradigm: making transcultural connections in a scientific translation of
      acupuncture.
AB  - This paper examines the ways in which the acupuncture phenomenon is translated
      into scientific language through the mobilization of functional magnetic
      resonance imaging. In doing so, it explores how differences between science and
      traditional medicine are bridged and negotiated through an open-ended tuning
      process among heterogeneous elements. By showing the constructive interaction
      between traditional medicine and science, I aim to refute a conception of East
      Asian medicines as culturally bounded and to provide an interpretation of
      transculturalism that emphasizes its diverse and hybrid formations. Particularly,
      in order to explain the scientific translation of acupuncture, I refer to Andrew
      Pickering's "mangle of practice" as an alternative to Thomas Kuhn's paradigm.
      Adopting a performative perspective rather than a representational one with
      regard to science, I read the scientific interpretation of acupuncture as an
      interactive stabilization between the acupuncture phenomenon, neurological
      theory, and the material procedure of the MRI machine.

PMID- 16413096
TI  - Physico-chemical characterization and transfection efficacy of cationic liposomes
      containing the pEGFP plasmid.
AB  - Cationic liposomes-DNA complexes (lipoplexes) are largely used in gene delivery.
      Deciphering specific chemical and physical properties of lipoplexes is a
      necessary step to unravel the mechanisms underlying transfection and to improve
      transfection efficacy in each experimental model. In the present paper we
      investigated the physico-chemical features of lipoplexes containing a plasmid
      encoding for the GFP protein, in order to correlate these results with
      transfection efficacy. Cationic unilamellar vesicles (mean diameter 100 nm) were
      prepared, from the cationic DC-Chol lipid and the zwitterionic phospholipid DOPE.
      The two components of the liposome bilayer were used at molar ratio close to
      unity. ESR spectra were recorded and zeta potential zeta was measured on
      liposomes complexed with the plasmid. One of the main points of interest in this
      paper resided in the fact that both kinds of measurements were carried out in the
      same conditions (i.e. lipid concentration, medium composition, and pH) employed
      for cell transfection experiments. Transfection was performed on CHO cells; the
      percentage of fluorescent cells was evaluated and compared with the above physico
      chemical features. It emerged that the composition and pH of the medium, the
      lipoplex/cell ratio, as well as the amount of lipoplex added to the cell culture
      were critical parameters for transfection efficacy. Finally, lipoplex surface
      charge played a fundamental role to achieve a high transfection level.

PMID- 16413095
TI  - Pulsus paradoxus and pericardial effusion.

PMID- 16413094
TI  - Carbaryl inhibits basal and FSH-induced progesterone biosynthesis of primary
      human granulosa-lutein cells.
AB  - Carbaryl is known to impede female reproductive function, however, the mechanisms
      through which the adverse effects are mediated are not clearly elucidated. In
      order to get insight into the mechanisms, this study was conducted to raise fresh
      concerns about the potential effects of carbaryl on steroidogenesis by primary
      human granulosa-lutein cells (hGLCs) and explore the possible nature of this
      action. hGLCs were co-incubated with various concentrations of carbaryl at 0, 1,
      5, 25, 125 micromol/L for 24 h to examine effects of this carbamate pesticide on
      progesterone accumulation. We observed that the carbaryl inhibited basal and FSH
      induced progesterone production in a dose-dependent manner. We also investigated
      the effects of carbaryl on 22(R)-hydroxycholesterol (22R-HC)-stimulated
      progesterone yield, basal and FSH-stimulated StAR gene expression and cyclic
      adenosine monophosphate (cAMP) production, as well as forskolin (non-specific
      activator of adenylyl cyclase)-induced progesterone and cAMP production of hGLCs.
      We found that the decreased progesterone biosynthesis was accompanied with a
      reduced cAMP abundance on both basal and FSH-induced condition. Furthermore, our
      results demonstrated that the 22R-HC could remove the carbaryl-induced restraint
      of progesterone biosynthesis, suggesting that carbaryl caused a disruption of
      cholesterol transport across mitochondrial membranes, which was further confirmed
      by the observation that carbaryl inhibited the gene expression of steroidogenic
      acute regulatory protein (StAR). In addition, the inhibitory effects of carbaryl
      on progesterone and cAMP production were completely reversed by addition of
      forskolin to the cell culture, which indicated a repaired site on the upstream
      components of adenylate cyclase or adenylate cyclase per se by carbaryl in the
      cAMP-mediated signal pathway. All the effects mentioned above were not due to a
      detrimental action of carbaryl on cell viability by MTS assay. In conclusion,
      carbaryl may inhibit steroidogenesis, at least in part, by obstructing the
      delivery of cholesterol over mitochondrial membranes and attenuating cAMP
      generation.

PMID- 16413097
TI  - Decision making under uncertainty in case of soil remediation.
AB  - Decisions on soil remediation are one of the most difficult management issues of
      municipal and state agencies. The assessment of contamination is uncertain, the
      costs of remediation are high, and the impacts on the environment are multiple.
      This paper presents a general, transparent, and consistent method for decision
      making among the remediation alternatives. Soil washing, phytoremediation, and no
      remediation are exemplarily considered. Multi-criteria utility functions
      including (a) the cost of remediation (b) the impact on human health and
      agricultural productivity, and (c) the economic gain after remediation are
      constructed using probability density functions representing contamination for
      all site coordinates. Herewith, the probability of different types of (i) correct
      decisions such as a hit or a true rejection and (ii) erroneous decisions such as
      a false alarm or miss are examined. The decision theoretic model is applied to a
      case study on heavy metal contaminated soil. This case study reveals the non
      linear structure of multi-criteria-decision making. The case study shows that the
      geostatistical uncertainties of the log-normal distributed soil contamination
      must be taken into account: When uncertainties are not considered and the
      utilities are assessed according to the estimated value for a spatial unit, only
      few (N=26) spatial units result where the utility score of the alternative soil
      washing are higher than the utility score to the no remediation alternative.
      However, when taking into account geostatistical uncertainties of the log-normal
      soil distribution this number is about ten times greater (N=237). Furthermore,
      the use of 'maximizing expected utility' as decision rule is critical in that it
      may lead to a high probability of misses.

PMID- 16413098
TI  - Rapid extracorporeal shock wave lithotripsy treatment after a first colic episode
      correlates with accelerated ureteral stone clearance.
AB  - OBJECTIVES: To investigate the relationship between delay in extracorporeal shock
      wave lithotripsy (ESWL) after a first colic and subsequent time to complete stone
      clearance. METHODS: This prospective, non-randomized study included 94 patients
      treated with ESWL for unilateral solitary proximal ureteral stones after at least
      one episode of colic pain. Time between the first onset of colic pain and ESWL
      and stone clearance was recorded. The pretherapeutic degree of hydronephrosis has
      been assessed using ultrasound. RESULTS: Mean stone size was 7.9 +/- 2.3 mm and
      mean time before ESWL after a first colic was 93.4 +/- 143.5 h. At 3 months, 3
      patients were lost to follow-up. In 76.9% of patients stones were completely
      cleared and a further 3.3% harbored residual fragments < or =3 mm. Delay in
      treatment after a first colic correlated with subsequent time to stone clearance
      (p < 0.0001). Mean time to stone clearance in patients treated within 24h was 6.4
      +/- 6.3 days compared with 16.0 +/- 17.8 days for those treated later (p =
      0.008). Maximum stone diameter correlated with time to stone clearance (p =
      0.031), but the degree of hydronephrosis did not. CONCLUSIONS: Rapid ESWL after a
      first onset of colic pain resulted in accelerated stone clearance independent of
      the degree of hydronephrosis but had no impact on the need for auxiliary
      procedures.

PMID- 16413099
TI  - Prevention of bladder cancer: a review.
AB  - INTRODUCTION: Bladder cancer represents an ideal tumor model to test and apply
      cancer prevention strategies. In addition to reviewing the epidemiology of
      transitional cell carcinoma (TCC), we review the current status and the future
      directions of bladder cancer prevention. MATERIALS AND METHODS: A literature
      review of peer-reviewed articles which address bladder cancer prevention was
      performed. RESULTS: Pre-clinical and limited clinical data suggest that bladder
      cancer is responsive to efforts to delay or prevent its development in at-risk
      patients, and in reducing the risk of recurrence in patients with established
      disease. Many epidemiologic studies, however, investigating natural products,
      such as vitamins and herbal compounds, lack conclusive evidence of their
      chemopreventive effects. CONCLUSIONS: While many agents hold promise in the
      prevention of bladder cancer, none currently can be recommended as proven
      chemoprevention strategies. Improving the accuracy of patient risk assessment and
      identification of surrogate endpoint biomarkers are crucial to the testing of
      these strategies. Efficient study design will ensure rapid and substantial
      advances in the chemoprevention of bladder cancer.

PMID- 16413101
TI  - Supratrigonal VVF repair by modified O'Connor's technique: an experience of 26
      cases.
AB  - OBJECTIVE: To report the technical modifications of O'Connor's procedure and
      their outcome in 26 supratrigonal vesico vaginal fistulae. MATERIALS AND METHODS:
      Twenty-six cases of supratrigonal VVF (17 primary, 9 recurrent) were operated
      using the described modifications. It consisted of approaching the bladder
      transperitoneally, without dissecting the retropubic space, making a short
      sagittal or parasagittal cystotomy in between stay sutures, liberal use of
      bladder rotation flaps instead of midline closure, using single layer,
      continuous, closely placed, interlocking stitches for bladder as well as vaginal
      approximation and universal use of vascularised tissue interposition. RESULTS:
      Mean fistula size was 2.8 cm (range 1.0 to 3.7). Mean operative time was 104
      minutes, and blood loss was insignificant. Three patients required
      ureteroneocystostomy. All patients were dry after 2-3 weeks of suprapubic and per
      urethral catheter drainage. One patient persisted with stress urinary
      incontinence. No patient on follow up complained of features suggestive of
      prolonged ileus, peritonitis or adhesive intestinal obstruction. CONCLUSION:
      Modified O'Connor's repair is safe and achieves excellent functional results. It
      requires a shorter cystotomy instead of bi-valving of the bladder, thus minimizes
      tissue trauma, intraoperative blood loss and operating time. It also gives option
      of tailoring the cystotomy in sagittal or parasagittal line, according to the
      site and size of the fistula, and thus permits closure of fistula by rotation of
      bladder flap into the defect without any lateral traction on the bladder edges.
      Retropubic dissection and drainage of the retropubic space is also not required.

PMID- 16413100
TI  - Mitogen-activated protein kinase signaling is activated in prostate tumors but
      not mediated by B-RAF mutations.
AB  - OBJECTIVES: A dysregulated mitogen-activated protein kinase (MAPK) pathway plays
      an important role in various malignancies and is often mediated by mutations in
      several oncogenes (eg, RAF, RAS). B-RAF mutations, predominantly the specific
      V600E mutation and additional alterations in exons 11 and 15, were frequently
      detected in malignant melanomas, papillary thyroid tumors, and colorectal cancers
      with microsatellite instability (MSI). The present study investigated B-RAF
      mutations, MSI status, and activation of MAPK signaling in prostate tumors.
      METHODS: The V600E mutation of the B-RAF gene was analyzed using allele-specific
      polymerase chain reaction in 79 archival prostatic adenocarcinomas (pT1aG1 to
      pT3cG3, median Gleason score 6); exons 11 and 15 were sequenced. MSI status was
      determined using the National Cancer Institute consensus panel for hereditary
      nonpolyposis colorectal carcinoma (HNPCC) detection. Active MAPK signaling was
      investigated using immunohistochemistry for p44/ERK1 and p42/ERK2. RESULTS: No B
      RAF mutations could be detected. Six of 79 tumors showed MSI positivity. Active
      MAPK signaling was detected in 51% of the analyzed tumors. No correlation was
      found between MAPK activity and histopathologic/clinical characteristics.
      CONCLUSION: The most frequent B-RAF gene alterations are not involved in prostate
      carcinogenesis. MSI is infrequent in prostate cancer and is not linked to B-RAF
      mutations. MAPK signaling is frequently activated in prostate tumors and might be
      suitable for a therapeutic approach.

PMID- 16413102
TI  - Nerve sparing laparoscopic radical prostatectomy: our technique.
AB  - PURPOSE: To describe our technique of nerve sparing laparoscopic radical
      prostatectomy (LRP). We present the oncological and functional results (potency
      and urinary continence). MATERIAL AND METHODS: LRP has become standard at our
      institution based on experience with more than 2800 consecutive cases operated on
      between 1997 and 2005. From May 2003 to March 2005 a total of 677 LRP were
      performed, 425 consecutive patients candidates for a nerve sparing technique have
      been operated using the intrafascial approach. The challenge of our technique is
      to remove the prostate without any thermic and mechanic traumatism, avoiding
      dissection of outer layer. Oncological data were assessed by pathological
      examination and post-operative PSA level. Functional results were assessed with a
      self questionnaire. RESULTS: By pathological stage, 2 pT2a specimens (7.4%), 7
      pT2b specimens (21%), 44 pT2c specimens (24%), 63 pT3a specimens (43%), 11 pT3b
      specimens (46%) were found to have positive surgical margins (SMs). In 86
      specimen (59%) positive SMs were focal inframillimetric. Median follow-up was 11
      months (range 1-22). The continence rate (no leakage/no pad) was 95% at 6 months,
      confirmed at 12 months among 202 patients. For 137 patients, potency rate was
      58.5% at 12 months. CONCLUSION: Intrafascial LRP provides satisfactory results in
      regard to recovery of continence and sexual function. Long-term progression and
      survival outcome are necessary before this procedure should be offered as a
      replacement for interfascial nerve sparing technique.

PMID- 16413103
TI  - The 2002 AJCC pT2 substages confer no prognostic information on the rate of
      biochemical recurrence after radical prostatectomy.
AB  - INTRODUCTION: We examined the prognostic value of AJCC pT2 substages in
      prediction of biochemical recurrence (BCR) after radical prostatectomy (RP), in
      European patients. METHODS: A cohort of 1726 RP patients with pT2N0 prostate
      cancer (PCa) was studied. Multivariate Cox regression models addressed the
      association between either the 1997 or 1992/2002 pT2 substages after controlling
      for total PSA, primary and secondary pathologic Gleason scores and surgical
      margin status and time to PSA recurrence (PSA >0.1 and rising) after RP.
      Regression coefficients were then used to test the predictive accuracy of
      multivariate models in a nomogram setting. RESULTS: PSA recurrence occurred in 80
      (4.6%) patients. Mean and median times to recurrence were respectively 28.9 and
      24.4 months. In univariate analyses, neither the 1997 (p = 0.48) nor the
      1992/2002 pT2 substages (p = 0.054) were predictive of recurrence. In
      multivariate analyses the lack of significance persisted (1997 p = 0.709;
      1992/2002 p = 0.124). When either the 1997 or 1992/2002 pT2 substages were added
      to a multivariate nomogram without pT2 substage information, its accuracy
      respectively decreased by 0.8% and 1.1%. CONCLUSION: Our data indicate that pT2
      substages offer no incremental value relative to pre-treatment total PSA,
      surgical margin status and pathologic Gleason scores. Therefore, it might be
      postulated that it is sufficient to confirm organ confinement according to
      Partin's pathologic staging.

PMID- 16413104
TI  - Infrequent microsatellite instability in urothelial cell carcinoma of the bladder
      in young patients.
AB  - OBJECTIVE: Defects in the DNA mismatch repair result in microsatellite
      instability (MSI), which characterise most tumours related to the hereditary non
      polyposis colorectal cancer syndrome and some sporadic tumours. Several studies
      have reported the occurrence of MSI in urothelial cell carcinoma (UCC) of the
      bladder with a particularly high incidence in tumours from young patients. In
      this study, we have evaluated the occurrence of MSI in primary bladder UCC
      arising in seventeen young patients selected for being below 45 years of age at
      diagnosis. METHODS: Microsatellite analysis has been performed using the panel of
      five quasimonomorphic mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-24, NR
      27) recently recommended to detect MSI tumours. The original Bethesda panel
      including BAT-25, BAT-26 and three dinucleotide repeats (D2S123, D5S346, D17S250)
      has further been studied in 10 UCC samples. RESULTS: MSI has been observed in
      only one of the 17 bladder UCC studied. Using the original Bethesda panel,
      identical results were obtained, indicating that the panel of five mononucleotide
      markers adequately detected MSI in UCC tumours. CONCLUSIONS: Our data indicate
      that classical MSI affecting mono- or di-nucleotides are rarely involved in
      bladder UCC developing in young patients. Further studies using gold standard
      criteria would help clarifying the involvement of MSI in the pathogenesis of
      bladder UCC.

PMID- 16413106
TI  - The role of 11beta-hydroxysteroid dehydrogenases in the brain.
AB  - Glucocorticoids have a plethora of effects within the body to maintain
      homeostasis. In the brain they modify learning, memory and fear behaviours as
      well as regulating their own secretion by a negative feedback action. 11Beta
      hydroxysteroid dehydrogenases (11beta-HSDs) are glucocorticoid metabolising
      enzymes that modify actions of glucocorticoids in a tissue specific manner.
      11Beta-HSD1 regenerates active glucocorticoids from their inactive 11-keto
      derivatives, hence boosting tissue levels of corticosterone and cortisol. Removal
      of this enzyme (11beta-HSD1-/- mice) results in apparent lower intra-hippocampal
      corticosterone levels and reduces glucocorticoid-associated cognitive decline
      during ageing. This low corticosterone tissue environment is maintained even
      though there is a hyperactive hypothalamic-pituitary-adrenal axis and elevated
      basal and stress-induced plasma corticosterone levels. Conversely, the major
      central effects of 11beta-HSD2 are seen in development, as expression of 11beta
      HSD2 is high in fetal and certain parts of the neonate brain, but is confined to
      a few discrete regions of the adult brain. 11Beta-HSD2 acts as a dehydrogenase,
      inactivating corticosterone or cortisol through conversion to 11
      dehydrocorticosterone and cortisone. Loss of 11beta-HSD2 from the fetus and
      fetally derived tissues results in altered development of the cerebellum in the
      neonatal period and a life-long phenotype of anxiety, consistent with early life
      glucocorticoid programming.

PMID- 16413105
TI  - Long term results of neuromodulation by sacral nerve stimulation for lower
      urinary tract symptoms: a retrospective single center study.
AB  - OBJECTIVE: To analyse the influence of technical improvements of Sacral Nerve
      Stimulation (SNS) on the incidence of surgical interventions and subjective long
      term results of SNS. METHODS: Retrospective, transversal study analyzing records
      of implanted patients at our department of Urology. RESULTS: Of 149 patients
      analyzed, 107 had overactive bladder symptoms and 42 had urinary retention. Mean
      follow-up was 64,2 (sd = 38,5) months. In the whole group 194 adverse events
      occurred. 6 Patients had infection in their implanted system, one was explanted
      for infection. Most events could be solved by giving advice or by reprogramming
      the stimulator. 129 reoperations have been performed and 21 patients had their
      system explanted. Analysis of the data shows a striking difference in the
      incidence of reoperations, but small differences in subjective results in the
      groups of patients implanted before or after 1996, suggesting that a proactive
      approach towards adverse events is worthwhile. CONCLUSIONS: SNS gives lasting
      benefit in patients with refractory symptoms of overactive bladder and non
      obstructive urinary retention. The differences in outcomes and incidence of
      reoperation can be attributed to the learning curve and technical and surgical
      improvements in the application of SNS.

PMID- 16413107
TI  - Integration of morphological and cytophysiological studies on estrogen receptor.
AB  - Ultrastructural and immunocytochemical studies of an intra-nuclear particle, the
      perichromatin granule (PCG), demonstrated the presence of processed mRNA in this
      structure. Ovariectomy caused an increase in the number of PCGs in uterine cells
      and administration of estradiol drastically reduced the nuclear pool of PCGs in
      15 min. In vitro studies demonstrated that this depletion was accompanied by an
      increase of the export of previously synthesized RNA. Similar quantitative
      changes of the abundance of PCG and of the rate of the export of RNA were found
      in ventral prostate after orchiectomy and testosterone restitution, as well as in
      the target cells of FSH, LH, TSH, and ACTH. These results taken together led us
      to conclude that PCGs constitute an intra-nuclear compartment of a few processed
      mRNA in equilibrium with transcription and export. This mRNA is rapidly
      transferred to the cytoplasm by specific hormone signals.

PMID- 16413109
TI  - Odorant receptors and olfactory-like signaling mechanisms in mammalian sperm.
AB  - Since their discovery in 1991, members of the odorant receptor (OR) family have
      been found in various ectopic tissues, including testis and sperm. It took,
      however, more than a decade for the first mammalian testicular ORs to be
      functionally characterized and implicated in a reproductively relevant scenario.
      Activation of hOR17-4 and mOR23 in human and mouse sperm, respectively, mediates
      distinct flagellar motion patterns and chemotactic behavior in various bioassays.
      For hOR17-4, receptor function and downstream signal transduction events are
      shown to be subject to pharmacological manipulation. Further insight into the
      basic principles that govern sperm OR operation as well as into the molecular
      logic that underlies OR-mediated signaling could set the stage for pioneering
      future applications in procreation and/or contraception.

PMID- 16413108
TI  - Transcriptome analyses of male germ cells with serial analysis of gene expression
      (SAGE).
AB  - Serial analysis of gene expression (SAGE) provides an alternative with additional
      advantages to microarrays for studying gene expression during spermatogenesis.
      The digitized transcriptome provided by SAGE of purified mouse germ cells
      identified 27,504 species of transcripts expressed in type A spermatogonia,
      pachytene spermatocytes, and round spermatids. Over 2700 of these transcripts
      were novel. Computational analyses allowed the identification of clusters of co
      regulated genes, cell-specific promoter modules, cell-specific biological
      processes, as well as "preferential" biological networks in different cell types.
      These analyses provided potential drug targets for interference of specific
      pathways at different stages of spermatogenesis. Analyses of the transcriptomes
      revealed the prominent role of cytochrome c oxidase in germ cells and suggest a
      novel role for this enzyme in cytochrome c-mediated apoptosis in spermatogonia. A
      number of genes were shown to undergo differential splicing during
      spermatogenesis giving rise to cell-specific splice variants.

PMID- 16413110
TI  - Role of epididymal receptor HE6 in the regulation of sperm microenvironment.
AB  - HE6 (GPR64) is a highly conserved, tissue-specific heptahelical receptor of the
      human epididymis. The seven transmembrane (TM7) domains are a hallmark of G
      protein-coupled receptors (GPCRs) which have a proven history of being excellent
      therapeutic targets. Of all currently marketed drugs, >30% are modulators of
      specific heptahelical receptors, emphasizing the potential of HE6 as a target for
      pharmaceutical intervention. Targeted mutation of the mouse HE6 counterpart
      resulted in male infertility, further emphasizing its role as a candidate target
      for male contraception. However, the precise function of HE6, together with its
      potential ligand(s), and signal transduction pathways have remained largely
      unknown. On the basis of shared sequence motifs within the TM7 region, HE6 has
      been grouped into the B class of GPCRs. Within this class, HE6 belongs to the
      'large N-termini' family-B seven-transmembrane (LNB-TM7) receptors, also termed
      the adhesion-GPCRs. Members of this subgroup are 'orphan' receptors, and they all
      seem to be cleaved within a conserved GPCR proteolytic site (GPS) domain. The
      biological significance of the two-subunit architecture is still unknown. Clues
      to the function of HE6 within the epithelium of male excurrent ducts may come
      from its co-localisation with the apical actin cytoskeleton and from the down
      regulation in "knockout" male mice of various proteins specific to the initial
      segment.

PMID- 16413111
TI  - Role of estrogen in regulation of cellular differentiation: a study using human
      placental and rat Leydig cells.
AB  - Estrogen classically is recognized as a growth-promoting hormone. Recent evidence
      suggests that estrogens are also involved in a wide variety of cellular and
      physiological functions involving the central nervous system, immune system,
      cardiovascular system and bone homeostasis. Our studies in cytotrophoblasts and
      BeWo cells, demonstrated that 17beta-estradiol induces terminal differentiation
      of placental trophoblasts directly and this differentiation is coupled with an
      increased production of TGFbeta1, which, in turn, affects telomerase activity and
      telomerase associated components at the level of hTERT. Furthermore, using rats
      treated in vivo with either EDS or estradiol and in vitro Leydig cell cultures,
      we proposed that 17beta-estradiol mediated down-regulation of collagen IV alpha4
      expression could be one of the possible mechanisms for the inhibition of
      progenitor Leydig cell proliferation. In this review, we summarize the results
      from both the model systems, the human placental cytotrophoblast and rat Leydig
      cells to conclude that 17beta-estradiol has a unique stage-specific role in
      differentiation.

PMID- 16413112
TI  - Prenatal testosterone excess programs reproductive and metabolic dysfunction in
      the female.
AB  - Findings discussed in this review stress the importance of normal estrogen and
      androgen signaling at appropriate developmental time points in maintaining normal
      phenotypic expression, reproductive and metabolic function and document how
      inappropriate steroid signaling, at inopportune times can have undesirable
      outcomes. For example, inappropriate testosterone exposure during fetal life
      alters the developmental trajectory of the female culminating in a suite of
      disorders, which include intrauterine growth-retardation and postnatal catch up
      growth, phenotypic masculinization, reproductive neuroendocrine and ovarian
      disruptions leading to progressive loss of cyclicity and metabolic disruptions
      manifested as hyperinsulinemia.

PMID- 16413113
TI  - Influence of galangin on HL-60 cell proliferation and survival.
AB  - The effect of galangin, a flavonol component of India root spice and the 'herbal'
      medicine propolis, on HL-60 human leukaemia cell survival is characterised.
      Galangin (1-100 microM) exerted an antiproliferative effect that, with dose and
      exposure longevity, was progressively associated with an elevated hypodiploid DNA
      content and expression of the active form of caspase-3, principally prior to
      membrane damage. At >or=50 microM, plasmamembrane phosphatidylserine exposure was
      observed. There was no evidence for intracellular oxidative stress as an
      orchestrator of cytotoxicity and significant phagocyte-like differentiation was
      not detected. We discuss whether such cytotoxicity will be therapeutically
      exploitable or contribute to cancer prevention within a pharmacological or
      dietary context.

PMID- 16413114
TI  - An aqueous polysaccharide extract from the edible mushroom Pleurotus ostreatus
      induces anti-proliferative and pro-apoptotic effects on HT-29 colon cancer cells.
AB  - Anti-proliferative and pro-apoptotic activities of fractions of Pleurotus
      ostreatus were examined using HT-29 colon cancer cells in vitro. A hot-water
      soluble fraction of the mycelium of the liquid cultured mushroom was partially
      isolated and chemically characterized as a low-molecular-weight alpha-glucan. HT
      29 cells were exposed to the different isolates and significant inhibition of
      proliferation was obtained in a dose-dependent manner. Proliferation inhibition
      was shown to be the result of apoptotic induction because the pro-apoptotic
      molecules Bax and cytosolic cytochrome-c were upregulated. Fluorescence-activated
      cell sorter analyses of polysaccharide-treated HT-29 cells showed a high
      percentage of Annexin-positive cells. Here, we describe a newly identified low
      molecular-weight alpha-glucan with promising anti-tumorigenic properties, and
      demonstrate its direct effect on colon cancer cell proliferation via induction of
      programmed cell death.

PMID- 16413116
TI  - The tumor microenvironment in the post-PAGET era.
AB  - The research area of tumor microenvironment is considered, at present, to be an
      important factor in tumorigenesis and especially in tumor progression. The
      present mini review is focused on three principles characterizing the nature of
      the tumor microenvironment. We first discuss the regulatory functions of the
      tumor microenvironment and the complexity of the combinatorial signaling pathways
      operating in it. We then address the aspect that the tumor microenvironment
      incorporates both pro and anti malignancy factors and that a balance between
      these factors regulates tumor progression. Thirdly we provide evidence that the
      non-tumor cells in the tumor microenvironment and their products may be different
      from those of their counterparts residing in non-tumor microenvironments. The
      conclusion of this mini review is that the tumor microenvironment, by exerting
      regulatory functions and selective pressures drives cancer cells into one of
      several molecular evolution pathways thereby determining and shaping their
      malignancy phenotype.

PMID- 16413117
TI  - MEG detects neural consequences of anomalous nasalization in vowel-consonant
      pairs.
AB  - This study identifies a delay in the neuromagnetic activity evoked by passive
      auditory presentation of anomalous speech sound combinations. Vowel-consonant
      vowel (VCV) stimuli were constructed to manipulate vowel nasalization in
      violation of the patterns of English, in which vowel nasalization ordinarily
      arises as a predictable coarticulatory effect of anticipatory velum lowering for
      production of a following nasal consonant. For anomalous stimuli with V1 and C
      mismatched in nasalization, the neural response to C was delayed relative to
      congruent control stimuli with V1 and C matched for nasalization. As both
      anomalous and control stimuli represent linguistically possible speech sound
      sequences, the temporal disparity in evoked neuromagnetic activity in English
      speakers reflects a role for language-specific phonological knowledge at the
      earliest stages of auditory processing.

PMID- 16413115
TI  - 9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is
      accompanied by increased expression of RAR-beta but no change in cyclooxygenase
      2.
AB  - 9-cis-Retinoic acid (9cRA) binds both retinoic acid receptors (RARs) and retinoid
      X receptors (RXRs) and has been shown to be a potential chemopreventive agent
      both in lung cancer cell culture studies and in clinical trials studying former
      smokers. However, direct evidence of the efficacy of 9cRA against lung tumor
      development in vivo is lacking. In the present study, we determined whether
      treatment with 9cRA has the potential to inhibit lung carcinogenesis by
      upregulating RAR-beta and down-regulating COX-2 expression in the A/J mouse lung
      cancer model. A/J mice (n=14-15/group) were treated as follows: (1) Control (Sham
      treated); (2) NNK (100mg NNK/kg body weight); (3) NNK+9cRA (15mg/kg diet); and
      (4) NNK+celecoxib (a COX-2-specific inhibitor, 500mg/kg diet). Tumor incidence,
      tumor multiplicity, RAR-beta mRNA, COX-2 mRNA, and COX-2 protein levels in lung
      samples of mice were determined 4 months after carcinogen injection. The results
      showed that mice receiving 9cRA supplementation had significantly lower tumor
      multiplicity (48% reduction, P<0.05) and showed a trend toward lower tumor
      incidence (40% reduction, P=0.078), as compared with the mice given NNK alone.
      Although, celecoxib treatment resulted in greater declines in tumor incidence and
      tumor multiplicity (75 and 88%, respectively, P<0.05), the chemoprotective
      effects of celecoxib were accompanied by increased mortality while 9cRA treatment
      resulted in no weight-loss associated toxicity or mortality. Supplementation with
      9cRA was effective in increasing RAR-beta mRNA, but this increase was not
      accompanied by decreased levels of COX-2 mRNA or protein. These results suggest
      that 9cRA supplementation may provide protection against lung carcinogenesis and
      this effect may be mediated in part by 9cRA induction of RAR-beta, but not
      inhibition of COX-2 transcription.

PMID- 16413119
TI  - Short-term sensory learning does not alter parvalbumin neurons in the barrel
      cortex of adult mice: a double-labeling study.
AB  - We have previously reported that a classical conditioning paradigm involving
      stimulation of a row of facial vibrissae produced expansion of the cortical
      representation of the activated vibrissae ("trained row"), this was demonstrated
      by labeling with 2-deoxyglucose in layer IV of the barrel cortex. We have also
      shown that functional reorganization of the primary somatosensory cortex is
      accompanied by an increase in the density of small GABAergic cells and glutamate
      decarboxylase 67-positive neurons in the hollows of barrels representing the
      "trained row." GABA neurons of the rat neocortex co-localize with calcium-binding
      proteins [parvalbumin, carletinin, calbindin D28k] and neuropeptides (vasoactive
      intestinal polypeptide, somatostatin). In the present study we have examined
      GABAergic parvalbumin-positive, interneurons in the cortical representation of
      "trained" facial vibrissae after short-term aversive training, in order to
      determine whether the observed changes in glutamate decarboxylase 67-positive
      neurons are accompanied by changes in parvalbumin-positive neurons. Using double
      immunofluorescent staining, it was found that (i) all parvalbumin-positive
      neurons in the barrel hollows were glutamate decarboxylase 67-positive, (ii)
      following aversive training density of glutamate decarboxylase 67-positive
      neurons in barrel hollows increased significantly compared with controls and
      (iii) density glutamate decarboxylase 67-positive/parvalbumin-positive neurons in
      "trained" barrel hollows did not change compared with controls. This study is the
      first to demonstrate that the density of double-labeled glutamate decarboxylase
      67-positive/parvalbumin-positive neurons does not alter during cortical
      plasticity, thus suggesting that some other population (i.e. parvalbumin
      negative) of GABAergic interneurons is involved in learning-dependent changes in
      layer IV of the barrel cortex.

PMID- 16413118
TI  - Demonstration of the expression and the enzymatic activity of N
      acetylglucosaminyltransferase IX in the mouse brain.
AB  - We recently reported on a brain-specific beta1,6-N-acetylglucosaminyltransferase
      IX (GnT-IX, also referred to as GnT-VB), a GnT-V homologue, which acts on alpha
      linked mannose of N-glycans and O-mannosyl glycans. To distinguish functions of
      GnT-IX with GnT-V, we examined the distribution of GnT-IX and GnT-V transcripts
      in mouse tissues by Northern blot analysis. The two enzymes were differentially
      expressed as has previously been observed in human tissues. GnT-IX transcripts
      were restricted to the cerebrum, cerebellum, thymus and testis, whereas GnT-V
      transcripts were expressed ubiquitously in mouse tissues. To investigate the
      localization of these enzymes in mouse tissues in more detail, a polyclonal
      antibody against GnT-IX was prepared. The antibody specifically recognized GnT
      IX, but not GnT-V, in the Golgi apparatus, as confirmed by the use of GnT-IX and
      GnT-V transfectants. In agreement with the Northern blot analysis data, an
      immunohistochemical study showed substantial expression of GnT-IX in the brain,
      while no expression was observed in the liver. Moreover, to exclude GnT-V
      contamination, we performed an enzymatic assay for GnT-IX using a Mgat5 (GnT-V)
      null mouse brain as an enzyme source and found the enzymatic activities do, in
      fact, exist in mouse brain. The reaction product was confirmed by high
      performance liquid chromatography and mass spectrometry. These results
      demonstrate, for the first time, that GnT-IX protein is actually expressed and
      may function as a glycosyltransferase in the brain.

PMID- 16413120
TI  - Survival and morphology of auditory neurons in dissociated cultures of newborn
      mouse spiral ganglion.
AB  - We have systematically characterized neuronal survival and growth in cultures
      derived from newborn/postnatal day 1 mouse cochlea. Dissociated cultures of the
      cochlear spiral ganglion provide an experimental environment in which to examine
      molecular mechanisms of survival, development and physiology of auditory neurons.
      To relate survival to the total number of neurons present in the source tissue,
      three cochleas from different newborn CD-1 mice were embedded in Araldite resin
      and serially sectioned at 5 mum thickness. All neurons were counted. To avoid
      overcounting, each section served as a lookup section for the next, giving 8240+/
      423 (S.D.) neurons per ganglion. Cultures maintained in the presence of adjacent
      non-neural tissue, brain-derived neurotrophic factor, neurotrophin 3, leukemia
      inhibitory factor (LIF) and 10% fetal bovine serum returned the best overall
      survival (30%) at 42 h post-plating. Best overall survival required the
      continuous presence of a serum component(s) larger than 100,000 MW. Plating
      efficiency (number of neurons that attach to the well after 4 h) was similar in
      the presence or absence of LIF. Inclusion of LIF maintained 100% survival of
      plated neurons over 42 h of culture; without LIF, a large fraction of the neurons
      did not survive. LIF appeared to maintain survival by preferentially preserving a
      population of bipolar neurons, while having little effect on the number of
      monopolar neurons. This work provides quantitative measures of survival and
      morphology of auditory neurons in vitro. The results support the idea that
      survival of spiral ganglion neurons in vivo may depend on interactions with
      adjacent, non-neural tissue and raise the possibility that maintenance of bipolar
      morphology after hair cell damage may require biochemical mechanisms in addition
      to those induced by neurotrophins.

PMID- 16413122
TI  - Possible role of mouse cerebellar nitric oxide in the behavioral interaction
      between chronic intracerebellar nicotine and acute ethanol administration:
      observation of cross-tolerance.
AB  - Many studies have reported cross-tolerance between nicotine and ethanol.
      Previously we demonstrated that intracerebellar nicotine attenuates ethanol
      induced motor impairment. In this study, intracerebellar nicotine (0.625, 2.5, 5
      ng; once daily for five days) significantly attenuated ethanol-induced motor
      impairment in a dose-dependent fashion suggesting the development of cross
      tolerance between nicotine and ethanol in male CD-1 mice. Using the same
      paradigm, intracerebellar nicotine (5 ng) microinfused for 1, 2, 3, 5, 7 days
      significantly attenuated ethanol-induced motor impairment in all groups except
      the 1-day treatment group. Cross-tolerance, which developed optimally in 5-day
      nicotine treatment group, was reversible and detectable up to 40 h post-nicotine
      microinfusion. Intracerebellar microinfusion of hexamethonium (1 mug once daily
      for 5 days): (i) did not alter ethanol-induced motor impairment indicating no
      tonic nicotine receptor involvement; (ii) 10 min prior to daily intracerebellar
      nicotine treatment virtually abolished the cross-tolerance between nicotine and
      ethanol indicating nicotinic acetylcholine receptor participation; (iii) when
      microinfused 10 min after daily intracerebellar nicotine treatment, failed to
      abolish the cross-tolerance which suggested possible participation of downstream
      second messenger mechanisms. Chronic intracerebellar microinfusion of nicotine:
      (i) failed to attenuate acute pentobarbital (25mg/kg i.p.)-induced motor
      impairment; and (ii) produced no change in normal motor coordination when
      followed by saline injection. Finally, the cerebellar concentration of total
      nitric oxide products (nitrite+nitrate; NO(x)); (i) was increased after 5-day
      intracerebellar nicotine; (ii) was decreased by acute ethanol administration; and
      (iii) decreased due to acute ethanol administration which was opposed by chronic
      intracerebellar nicotine treatment. These results support a functional
      correlation between the cerebellar nitric oxide production and ethanol-induced
      motor impairment and suggest possible participation of nitric oxide as a factor
      in the observed cross-tolerance between nicotine and ethanol.

PMID- 16413126
TI  - Dopamine-D1 and -D2 receptors differentially regulate synapsin II expression in
      the rat brain.
AB  - We previously demonstrated that chronic treatment with the dopamine-D2 receptor
      antagonist, haloperidol, increases mRNA and protein content of the
      phosphoprotein, synapsin II, in the rat striatum. Since dopamine-D2 receptor
      antagonism and dopamine-D1 receptor blockade can have opposing effects on gene
      expression, the present investigation compared the effects of haloperidol with
      those of the dopamine-D1 receptor antagonist, R-[+]-7-chloro-8-hydroxy-3-methyl-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390), on the expression of
      synapsin II protein. Haloperidol and SCH23390 respectively elevated and reduced
      concentrations of the molecule in mouse primary midbrain cell cultures.
      Additional experiments revealed that the dopamine-D1 receptor agonist, R-[+]-1
      phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapezine-7,8-diol (SKF38393), upregulated the
      phosphoprotein in these cells. Furthermore, in vivo rat studies demonstrated that
      chronic haloperidol treatment increases synapsin II protein expression in the
      medial prefrontal cortex and nucleus accumbens, as was observed in the striatum.
      In contrast, chronic SCH23390 administration reduced concentrations of this
      protein in all of these regions, although the reductions seen in the medial
      prefrontal cortex were insignificant. Neither haloperidol nor the dopamine-D1
      receptor antagonist affected synapsin I protein expression in any of the studied
      brain areas. Based on these findings, we propose dopamine receptors may
      specifically regulate synapsin II expression through a cyclic AMP-dependent
      pathway. Since synapsin II is involved in neurotransmitter release and
      synaptogenesis, and changes in synaptic efficacy and structure are suggested in
      schizophrenia as well as in haloperidol treatment, our findings offer insight
      into the mechanistic actions of the antipsychotic agent at the synaptic level.

PMID- 16413123
TI  - Serial analysis of gene expression in the hippocampus of patients with mesial
      temporal lobe epilepsy.
AB  - Hippocampal sclerosis constitutes the most frequent neuropathological finding in
      patients with medically intractable mesial temporal lobe epilepsy. Serial
      analysis of gene expression was used to get a global view of the gene profile in
      human hippocampus in control condition and in epileptic condition associated with
      hippocampal sclerosis. Libraries were generated from control hippocampus,
      obtained by rapid autopsy, and from hippocampal surgical specimens of patients
      with mesial temporal lobe epilepsy and the classical pattern of hippocampal
      sclerosis. More than 50,000 tags were analyzed (28,282, control hippocampus;
      25,953, hippocampal sclerosis) resulting in 9206 (control hippocampus) and 9599
      (hippocampal sclerosis) unique tags (genes), each representing a specific mRNA
      transcript. Comparison of the two libraries resulted in the identification of 143
      transcripts that were differentially expressed. These genes belong to a variety
      of functional classes, including basic metabolism, transcription regulation,
      protein synthesis and degradation, signal transduction, structural proteins,
      regeneration and synaptic plasticity and genes of unknown identity of function.
      The database generated by this study provides an extensive inventory of genes
      expressed in human control hippocampus, identifies new high-abundant genes
      associated with altered hippocampal morphology in patients with mesial temporal
      lobe epilepsy and serves as a reference for future studies aimed at detecting
      hippocampal transcriptional responses under various pathological conditions.

PMID- 16413121
TI  - Presynaptic localization of a truncated isoform of the type 2 corticotropin
      releasing factor receptor in the cerebellum.
AB  - It is now well established that corticotropin releasing factor is present in two
      major excitatory afferent systems to the cerebellum, namely climbing fibers and
      mossy fibers. Two major classes of corticotropin releasing factor receptors, each
      with unique binding characteristics, have been identified as type 1 and type 2.
      In this study we used an antibody made to the n-terminus of the type 2
      corticotropin releasing factor receptor. Characterization of this antibody showed
      that it strongly labeled a protein with a molecular weight of 16-32 kDa and only
      faintly labels a 62-83 kDa protein. The lower molecular weight protein
      corresponds to the weight of a recently described truncated isoform of this
      receptor that is designated corticotropin releasing factor-type 2alpha-truncated
      isoform. We carried out transfection paradigms using corticotropin releasing
      factor-type 2alpha-truncated isoform constructs and confirmed that the antibody
      recognized the truncated isoform of the type 2 corticotropin releasing factor
      receptor. Further, light and electron microscopic studies were carried out in
      mice and rats to define the distribution of the truncated receptor.
      Immunoreactivity is evident in the basal region of many, but not all Purkinje
      cell bodies and their initial axonal segments, as well as the initial axonal
      segments of isolated Golgi cells, and cerebellar nuclear neurons. In addition,
      punctate elements in the molecular layer were immunolabeled. The localization of
      the receptor to the initial segment of Purkinje cells was confirmed with electron
      microscopy. Further, the punctate labeling in the molecular layer was localized
      to parallel fibers and their terminals. In conclusion, evidence has been
      presented to show that distinct isoforms of the corticotropin releasing factor
      receptor are present in the cerebellum. The complex interactions between
      corticotropin releasing factor and other members of the corticotropin releasing
      factor family of peptides with both pre- and postsynaptic receptors support a
      growing concept that corticotropin releasing factor plays an important role in
      modulating activity in cerebellar circuits and ultimately in controlling motor
      behavior.

PMID- 16413127
TI  - Persistent calcium current in rat suprachiasmatic nucleus neurons.
AB  - The suprachiasmatic nuclei contain the primary circadian clock, and
      suprachiasmatic nuclei neurons exhibit a diurnal modulation of spontaneous firing
      rate. The present study examined the voltage-gated persistent Ca(2+) current, in
      acutely isolated rat suprachiasmatic nuclei neurons using a ramp-type voltage
      clamp protocol. Slow triangular voltage-clamp commands from a holding potential
      of -85 mV to +5 mV elicited inward current (100-400 pA) that was completely
      blocked by Cd(2+). This current showed little or no hysteresis, and was
      identified as persistent Ca(2+) current. The threshold for persistent Ca(2+)
      current ranged between -60 and -45 mV, and it was maximal at about -8 mV.
      Nifedipine at 10-20 microM blocked 80-100%. To assess the role of persistent
      Ca(2+) current in the generation of spontaneous action potentials in both acutely
      isolated and intact suprachiasmatic nuclei neurons, the effect of Cd(2+) and
      nifedipine on firing rate was studied using on-cell recording. Application of
      Cd(2+) exerted a weak excitatory effect and nifedipine had no significant effect
      on the spontaneous firing rate of isolated suprachiasmatic nuclei neurons. In all
      intact suprachiasmatic nuclei neurons in slice preparations (n=15), Cd(2+) slowly
      inhibited spontaneous firing; in high-frequency firing cells (four of 15), a
      transient increase of firing rate preceded inhibition. No significant effect of
      nifedipine on firing rate of intact suprachiasmatic nuclei neurons was found.
      Therefore, persistent Ca(2+) current itself (as carrier of charge) does not
      appear to contribute significantly to spontaneous firing of suprachiasmatic
      nuclei neurons. A slowly developing inhibitory effect of Cd(2+) on spontaneous
      firing of intact suprachiasmatic nuclei neurons in slice preparations may be due
      to penetration of Cd(2+) through Ca(2+) channels, and its subsequent effect on
      intracellular mechanisms, while the transient increase of firing rate in high
      frequency firing neurons is probably due to inhibition of Ca(2+)-activated K(+)
      current.

PMID- 16413130
TI  - Cyclin-dependent kinase 5, Munc18a and Munc18-interacting protein 1/X11alpha
      protein up-regulation in Alzheimer's disease.
AB  - Besides formation of neurofibrillary tangles and neuron loss, the Alzheimer's
      disease brain is characterized by neuritic plaques consisting of beta-amyloid
      peptide deposits and impaired neurotransmission. The proteins Munc18a, Munc18
      interacting protein 1 and Munc18-interacting protein 2 mediate exocytosis and
      decrease beta-amyloid peptide formation. Cyclin-dependent kinase 5 and its
      activator p35 disrupt Munc18a-syntaxin 1 binding, thereby promoting synaptic
      vesicle fusion during exocytosis. We investigated protein levels of the signaling
      pathway: p35, cyclin-dependent kinase 5, Munc18a, syntaxin 1A and 1B, Munc18
      interacting protein 1 and Munc18-interacting protein 2 in Alzheimer's disease
      cortex and found that this pathway was up-regulated in the Alzheimer's disease
      parietal and occipital cortex. In the cortex of transgenic Tg2576 mice over
      expressing human beta-amyloid precursor protein with the Swedish mutation known
      to lead to familial Alzheimer's disease, which have substantial levels of beta
      amyloid peptide but lack neurofibrillary tangles and neuron loss, no alterations
      of protein levels were detected. These data suggest that the pathway is enhanced
      in dying or surviving neurons and might serve a protective role by compensating
      for decreased neurotransmission and decreasing beta-amyloid peptide levels early
      during the progression of Alzheimer's disease.

PMID- 16413125
TI  - Selective labeling of central and peripheral sensory neurons in the developing
      zebrafish using P2X(3) receptor subunit transgenes.
AB  - The two paralogous P2X receptor subunit genes p2rx3.1 and p2rx3.2 are selectively
      expressed in overlapping, but unique, patterns of sensory neurons in the
      developing zebrafish. We constructed a series of transgenes derived from both
      genes using the recombineering technique. Transgenes utilizing either enhanced
      green fluorescent protein or monomeric red fluorescent protein-1 were shown to be
      expressed with the same spatial and temporal patterns as the native genes. The
      p2rx3.1-derived transgenes labeled the vast majority of the Rohon-Beard neurons
      in the spinal cord and neurons of the trigeminal ganglia. The p2rx3.2-derived
      transgene labeled fewer Rohon-Beard and trigeminal neurons than what was observed
      for the p2rx3.1-derived transgenes, but was also detected in neurons of the
      epibranchial ganglia. Three distinct populations of sensory neurons were
      detected: those expressing only one or the other paralog, and those expressing
      both paralogs. The fluorescent proteins encoded by the transgenes allowed for
      visualization of the neuronal somas as well as their peripheral and central
      projections. These reagents should prove extremely useful in providing the basis
      for future studies aimed at elucidating the developmental and physiological
      attributes of sensory neurons.

PMID- 16413131
TI  - Transient loss of terminals from non-peptidergic nociceptive fibers in the
      substantia gelatinosa of spinal cord following chronic constriction injury of the
      sciatic nerve.
AB  - It is well known that following peripheral nerve injury, there are numerous
      changes in neurotransmitter and neuropeptide expression in the superficial dorsal
      horn, the dorsal root ganglion and the periphery. Of particular interest are the
      relative contributions of two sub-types of unmyelinated C-fibers in the
      initiation and maintenance of chronic pain, the peptidergic, and the non
      peptidergic. Evidence gathered in recent years has led researchers to believe
      that the non-peptidergic nociceptive primary afferents are functionally distinct
      from their peptidergic counterpart. For our study, we used a well-established
      animal model of constriction neuropathy (the Kruger model) and studied Wistar
      rats at 5, 7, 10, 15 and 21 days after nerve lesion caused by the application of
      a fixed-diameter polyethylene cuff to the left sciatic nerve. Animals were
      assessed for the onset and evolution of mechanical allodynia using calibrated von
      Frey filaments and were additionally tested for thermal (heat and cold)
      hypersensitivity. Immunocytochemical detection of calcitonin gene-related peptide
      (CGRP) and isolectin B4 (IB4) binding was used to visualize the dorsal horn
      distribution of the boutons from the peptidergic and non-peptidergic fibers
      respectively. Using confocal microscopy and image analysis, we detected a
      significant decrease in the density of IB4-labeled boutons, ipsilateral to the
      lesion, at seven and 10 days following nerve injury. The density of IB4-labeled
      varicosities retuned to control levels by 15 days. There were no significant
      changes in the density of CGRP-labeled varicosities at all time points examined.
      Applying electron microscopy, we initially detected degenerative changes in the
      central elements of type I glomeruli and then a considerable reduction in their
      number followed by recovery at 15 days post-lesion. As the central boutons of
      type Ia represent varicosities from the fibers which bind IB4, the
      ultrastructural changes confirmed that there was a bona fide transient loss of
      varicosities, not simply a loss of IB4 binding. These data indicate that, in this
      animal model, morphological changes in the nociceptive C-fiber input of the rat
      dorsal horn are restricted to the non-peptidergic sub-population and are
      transient in nature. Furthermore, such changes do not correlate with the time
      course of the allodynia.

PMID- 16413132
TI  - Peptidergic sensory and parasympathetic fiber sprouting in the mucosa of the rat
      urinary bladder in a chronic model of cyclophosphamide-induced cystitis.
AB  - In this study, we used a well-established animal model to investigate changes in
      the peptidergic and parasympathetic innervation of the bladder following chronic
      bladder inflammation. Adult female Sprague-Dawley rats were injected with either
      70 mg/kg cyclophosphamide diluted in saline, i.p., once every 3 days or saline.
      After 10 days, all animals were tested for urinary frequency and number of low
      volume voids, as well as symptoms of spontaneous pain. At the end of 12 days, all
      animals were perfused with histological fixatives and the urinary bladders
      processed for immunofluorescence using antibodies against calcitonin gene-related
      peptide and the vesicular acetylcholine transporter as markers, respectively, of
      peptidergic primary afferent fibers and parasympathetic efferent fibers. We show
      that animals treated with cyclophosphamide had inflamed bladders and displayed
      high urinary frequency as well as some indicators of spontaneous pain, such as
      piloerection and a rounded-back posture. Furthermore, they had a significant
      increase in the density of both parasympathetic and peptidergic sensory fibers in
      the bladder mucosa and an increase in peptidergic sensory fibers in the detrusor
      muscle. Based on these results, we suggest that peripheral sprouting of
      parasympathetic and peptidergic fibers could be a mechanism responsible for
      sensitization of the bladder, leading to urinary symptoms. Since we observed that
      the parasympathetic and peptidergic fibers often wrapped around one another and
      that their varicosities were very close, these two fiber populations may be
      interacting with each other to lead to and maintain sensitization. Future studies
      are required to establish the role of this fiber sprouting in bladder symptoms.

PMID- 16413124
TI  - Progesterone mediates gonadal hormone differences in tactile and thermal
      hypersensitivity following L5 nerve root ligation in female rats.
AB  - Sex differences in the magnitude of response to thermal and tactile stimuli have
      been demonstrated in both clinical and animal studies. Female rats typically
      display lower thresholds to painful stimuli and display more robust responses
      following nerve injury as compared with males. There is a body of evidence
      implicating the sex hormones in mediating this sex difference. In the present
      study, we sought to determine which gonadal hormones were involved in mediating
      the observed female hypersensitivity in female rats both prior to and following
      experimental nerve root injury using a chronic hormone replacement paradigm.
      Female rats were ovariectomized and hormone pellets containing 17beta-estradiol,
      progesterone (P), 17beta-estradiol+progesterone or placebo were implanted s.c.
      Our results demonstrate that only the group of female rats that received
      progesterone alone maintained the hypersensitive phenotype following ovariectomy,
      compared with gonadally intact male rats. This result was observed both in
      response to thermal stimuli in non-injured female rats and to thermal and tactile
      stimuli following L5 nerve root ligation, a model of low back pain associated
      with lumbar radiculopathy. Postmortem analysis of serum gonadal hormone
      concentrations demonstrates that the hormonal manipulations were successful and
      the exogenous hormones were similar to physiological levels observed in the sham
      ovariectomized controls. Taken together, these results demonstrate the critical
      role for progesterone in mediating enhanced female tactile and thermal
      hypersensitivity following L5 nerve root ligation.

PMID- 16413136
TI  - Does oxidative stress play a role in steroid-induced osteonecrosis models?

PMID- 16413128
TI  - Leptin enhances NR2B-mediated N-methyl-D-aspartate responses via a mitogen
      activated protein kinase-dependent process in cerebellar granule cells.
AB  - It is well documented that the hormone leptin regulates energy balance via its
      actions in the hypothalamus. However, evidence is accumulating that leptin plays
      a key role in numerous CNS functions. Indeed, leptin receptors are expressed in
      many extrahypothalamic brain regions, with high levels found in the hippocampus
      and cerebellum. In the hippocampus leptin has been shown to facilitate N-methyl-D
      aspartate receptor function and modulate synaptic plasticity. A role for leptin
      in cerebellar function is also indicated as leptin-deficient rodents display
      reduced mobility that is unrelated to obesity. Here we show that leptin receptor
      immunolabeling can be detected in cultured cerebellar granule cells, being
      expressed at the somatic plasma membrane and also concentrated at synapses.
      Furthermore, leptin facilitated NR2B N-methyl-D-aspartate receptor-mediated Ca2+
      influx in cerebellar granule cells via a mitogen-activated protein kinase
      dependent pathway. These findings provide the first direct evidence for a
      cellular action of leptin in cerebellar neurons. In addition, given that N-methyl
      D-aspartate receptor activity in the cerebellum is crucial for normal locomotor
      function, these data also have important implications for the potential role of
      leptin in the control of movement.

PMID- 16413134
TI  - PTSD and the HPA axis: differences in response to the cold pressor task among
      individuals with child vs. adult trauma.
AB  - Hypothalamic pituitary adrenal (HPA) axis and subjective stress response to a
      cold-water immersion task, the cold pressor task (CPT), in individuals (N=89)
      with post-traumatic stress disorder (PTSD) were examined. All tests were
      conducted at 08:00h after an overnight hospital stay. Plasma adrenocorticotrophin
      hormone (ACTH), cortisol, and subjective stress were examined at baseline and
      five post-task time points in controls (n=31), subjects with PTSD as a result of
      an index trauma during childhood (i.e. before age 18; n=25), and subjects with
      PTSD as a result of an index trauma as an adult (n=33). Approximately, 50% of
      individuals in both trauma groups were alcohol dependent, and the impact of this
      comorbidity was also examined. Subjects with PTSD, regardless of age of index
      trauma, had a less robust ACTH response as compared to controls. Regardless of
      the presence or absence of comorbid alcohol dependence, subjects with childhood
      trauma had lower cortisol at baseline and at all post-task measurement points and
      did not demonstrate the decrease in cortisol over the course of the 2h monitoring
      period seen in subjects with adult index trauma and controls. The findings reveal
      differences in the neuroendocrine response to the CPT in individuals with PTSD
      compared to control subjects, and differences in PTSD subjects when examined by
      age of index trauma.

PMID- 16413135
TI  - Influence of the estrous cycle on tolerance development to LPS-induced sickness
      behaviors in rats.
AB  - The relations between the estrous cycle, inflammatory responses and the
      development of tolerance to endotoxin were examined. Female Long-Evans rats were
      injected intraperitoneally with lipopolysaccharide (LPS; 200 microg/kg) or saline
      vehicle at 08:00h on either diestrus (D) or proestrus (P). Ninety-five minutes
      after injection locomotor activity was assessed in an automated non-novel open
      field for 20 min. To assess tolerance development to LPS, rats were re-injected
      at the next identical stage (i.e. 4 days later; groups: DD, PP) or at the
      alternate stage (i.e. 6 days later; groups: DP, PD) of the estrous cycle and
      locomotor activity was again assessed. On Test Day 1 all groups injected with LPS
      exhibited similar significant activity decrements, regardless of the stage of the
      estrous cycle. However, on Test Day 2 rats which received both injections of LPS
      during proestrus (PP) showed no signs of tolerance development, whereas rats in
      all other groups were tolerant to LPS. In a follow up study, the time between
      injections was extended to 8 days. Still the animals injected both times at
      proestrus showed no signs of tolerance to LPS after the second injection. Thus,
      the stages of the estrous cycle both at the time of initial exposure and of re
      exposure appear critical in the formation of behavioral tolerance to LPS in rats.

PMID- 16413133
TI  - Lithium increases bcl-2 expression in chick cochlear nucleus and protects against
      deafferentation-induced cell death.
AB  - Approximately 20-30% of neurons in the avian cochlear nucleus (nucleus
      magnocellularis) die following deafferentation (i.e. deafness produced by cochlea
      removal) and the remaining neurons show a decrease in soma size. Cell death is
      generally accepted to be a highly regulated process involving various pro
      survival and pro-death molecules. One treatment that has been shown to modify the
      expression of these molecules is chronic administration of lithium. The present
      experiments examined whether lithium treatment can protect neurons from
      deafferentation-induced cell death. Post-hatch chicks were treated with LiCl or
      saline for 17 consecutive days, beginning on the day of hatching. On the 17th
      day, a unilateral cochlea ablation was performed. Five days following surgery,
      the nucleus magnocellularis neurons were counted stereologically on opposite
      sides of the same brains. Lithium reduced deafferentation-induced cell death by
      more than 50% (9.8% cell death as compared with 22.4% in saline-treated
      subjects). Lithium did not affect cell number on the intact side of the brain.
      Lithium also did not prevent the deafferentation-induced decrease in soma size,
      suggesting a dissociation between the mechanisms involved in the afferent control
      of soma size and those involved in the afferent control of cell viability. A
      possible mechanism for lithium's neuroprotective influence was examined in a
      second set of subjects. Previous studies suggest that the pro-survival molecule,
      bcl-2, may play a role in regulating cell death following deafferentation.
      Tissues from lithium- and saline-treated subjects were examined using
      immunocytochemistry. Chronic administration of lithium dramatically increased the
      expression of bcl-2 protein in nucleus magnocellularis neurons. These data
      suggest that lithium may impart its neuroprotective effect by altering the
      expression of molecules that regulate cell death.

PMID- 16413129
TI  - Differential expression of Kv3.1b and Kv3.2 potassium channel subunits in
      interneurons of the basolateral amygdala.
AB  - The expression of Kv3.1 and Kv3.2 voltage-gated potassium channel subunits
      appears to be critical for high-frequency firing of many neuronal populations. In
      the cortex these subunits are mainly associated with fast-firing GABAergic
      interneurons containing parvalbumin or somatostatin. Since the basolateral
      nuclear complex of the amygdala contains similar interneurons, it is of interest
      to determine if these potassium channel subunits are expressed in these same
      interneuronal subpopulations. To investigate this issue, peroxidase and dual
      labeling fluorescence immunohistochemistry combined with confocal laser scanning
      microscopy was used to determine which interneuronal subpopulations in the
      basolateral nuclear complex of the rat amygdala express Kv3.1b and Kv3.2
      subunits. Antibodies to parvalbumin, somatostatin, calretinin, and
      cholecystokinin were used to label separate subsets of basolateral amygdalar
      interneurons. Examination of immunoperoxidase preparations suggested that the
      expression of both channels was restricted to nonpyramidal interneurons in the
      basolateral amygdala. Somata and proximal dendrites were intensely-stained, and
      axon terminals arising from presumptive basket cells and chandelier cells were
      lightly stained. Immunofluorescence observations revealed that parvalbumin+
      neurons were the main interneuronal subpopulation expressing the Kv3.1b potassium
      channel subunit in the basolateral amygdala. More than 92-96% of parvalbumin+
      neurons were Kv3.1b+, depending on the nucleus. These parvalbumin+/Kv3.1b+ double
      labeled cells constituted 90-99% of all Kv3.1b+ neurons. Parvalbumin+ neurons
      were also the main interneuronal subpopulation expressing the Kv3.2 potassium
      channel subunit. More than 67-78% of parvalbumin+ neurons were Kv3.2+, depending
      on the nucleus. However, these parvalbumin+/Kv3.2+ double-labeled cells
      constituted only 71-81% of all Kv3.2+ neurons. Most of the remaining neurons with
      significant levels of the Kv3.2 subunit were somatostatin+ interneurons. These
      Kv3.2-containing somatostatin+ interneurons constituted 27-50% of the
      somatostatin+ population, depending on the nucleus in question. These data
      suggest that both fast-firing and burst-firing parvalbumin+ interneurons in the
      basolateral amygdala express the Kv3.1b subunit. The significance of Kv3.2
      expression in some parvalbumin+ and somatostatin+ interneurons remains to be
      determined.

PMID- 16413138
TI  - Should slow coronary flow be considered as a coronary syndrome?
AB  - The concept of slow coronary flow was firstly described in 1972. This phenomenon
      indicates a coronary slow flow phenomenon in the absence of any known etiology.
      This phenomenon is not infrequently detected finding during routine coronary
      angiography, while it is, apparently, quite different from coronary slow flow
      phenomenon with evident causes. Slow coronary flow, consequently, should be
      distinguished from occurrence of slow flow in the context of coronary reperfusion
      therapy such as angioplasty or thrombolysis that is associated with different
      pathophysiological and clinical implications. Similarly, coronary slow flow
      associated with coronary spasm, coronary artery ectasia, myocardial dysfunction,
      valvular heart disease and certain connective tissue disorder involving coronary
      microvasculature is definitely need to be differentiated in patients with slow
      coronary flow. In addition, coronary slow flow phenomenon was also found in the
      situation from inadvertent air-embolism during angioplasty or due to an
      overlooked ostial lesion. Furthermore, the features of slow coronary flow are not
      in agreement with cardiac syndrome X. It is not certain, however, whether slow
      coronary flow phenomenon in the absence of any of known causes represents merely
      an angiographic curiosity or has special physiologic or therapeutic implications
      up to now. What kind of factors or etiologic reasons contributes to slow coronary
      flow? Is slow coronary flow an independent entity of coronary artery disease? All
      of those answers are still unknown and deserves further investigation. In our
      opinion, slow coronary flow without evident cause may represent a new entity of
      coronary heart disease. Therefore, we would like to consider it as a syndrome,
      and call it as a "slow coronary flow syndrome".

PMID- 16413137
TI  - Contrasting patterns of hospital admissions and mortality during heat waves: are
      deaths from circulatory disease a real excess or an artifact?
AB  - In old subjects exposed to extreme high temperature during a heat wave, studies
      have consistently reported an excess of death from cardio- or cerebro-vascular
      disease. By contrast, dehydration, heat stroke, acute renal insufficiency, and
      respiratory disease were the main causes of hospital admission in the two studies
      carried out in elderly during short spells of hot weather. The excess of
      circulatory disease reported by mortality studies, but not by morbidity studies,
      could be explained by the hypothesis that deaths from circulatory disease occur
      rapidly in isolated people before they reach a hospital. Since the contrasting
      patterns of hospital admission and mortality during heat waves could also be due
      to chance (random variation over time and space in the spectrum of diseases
      induced by extreme heat), and bias (poor quality of diagnosis on death
      certificate and other artifacts), it should be confirmed by a concurrent study of
      mortality and morbidity. Many heat-related diseases may be preventable with
      adequate warning and an appropriate response to heat emergencies, but preventive
      efforts are complicated by the short time interval that may elapse between high
      temperatures and death. Therefore, prevention programs must be based around rapid
      identification of high-risk conditions and persons. The effectiveness of the
      intervention measures must be formally evaluated. If cardio- and cerebro-vascular
      diseases are rapidly fatal health outcomes with a short time interval between
      exposure to high temperature and death, deaths from circulatory disease might be
      an useful indicator in evaluating the effectiveness of a heat watch/warning
      system.

PMID- 16413139
TI  - Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the
      counter (OTC) treatment.
AB  - Some old antihistamines were selective serotonin-reuptake inhibitors (SSRIs) and
      the SSRI effect was discovered by Nobel Laureate Professor Arvid Carlsson as
      early as 1969. Chlorpheniramine was the most active of the tested drugs, and it
      compares favourably with amitriptyline and imipramine with respect to actions on
      both serotonergic and noradrenergic neurons. Chlorpheniramine can be called a
      SSRI, since the blocking of 5HT is stronger than the effect on noradrenaline
      neurons; however it might also be called a selective serotonin and noradrenaline
      reuptake inhibitor (SSNRI) and be compared with new drugs, such as venlafaxine.
      Carlsson suggested the potential value of clinical studies of the antidepressant
      properties of this and related antihistamine drugs. But, in the event, no such
      trials were ever performed at the time. However, later clinical observations of
      the benefits of dex-chlorpheniramine treatment in panic disorder have been
      published. Clinical experience suggests that patients using chlorpheniramine, and
      having also a concomitant depression or panic disorder, may experience a return
      of symptoms when their old drug is changed to a new antihistamine lacking SSRI
      effects. Yet this phenomenon is not known to many doctors, and even less known to
      the large number of patients buying chlorpheniramine under various trade names
      over-the-counter (OTC) at a low price for self-treatment of hay fewer or as a
      cold remedy. Chlorpheniramine was introduced in USA under the name Chlor-Trimeton
      as long ago as July 1950, and is still on the market. Therefore, this SSRI is now
      over 50 years old. If chlorpheniramine had been tested in depression in the
      nineteen seventies, it is probable that a safe, inexpensive SSRI drug could have
      been used some 15 years earlier than fluoxetine - which became available in 1987.
      Chlorpheniramine might have been the first safe, non-cardiotoxic and well
      tolerated antidepressant. Billions of dollars in the development and marketing
      costs would have been saved, and the suffering of millions of patients
      alleviated.

PMID- 16413141
TI  - Effects of breaks in the interval cycle on temporal tracking in pigeons.
AB  - Two experiments examined the effects of inserting a break in a cyclic interval
      schedule on the temporal control of keypecking responses in pigeons. In
      Experiment 1, pigeons were exposed to intervals that changed from 45 to 15s and
      returned to 45 s. A break was inserted between the last 15-s and following 45-s
      interval and was in effect for either 0, 60, or 120 s. Either a blackout of
      lights in the test chamber or turning off the response key alone signaled breaks.
      In Experiment 2, we examined the effects of a wider range of breaks-0, 120, and
      360 s. Post-reinforcement pause (PRP) tracked changes in the interval requirement
      across all conditions. However, breaks in the schedule, even one lasting 360 s,
      did not disrupt the overall time course of responding. The only effect that a
      break had on temporal performance was an elevation in the rate of responding and
      a shorter PRP in the interval following a break. The results suggest that breaks
      did not affect the birds' memory for short intervals, and that the momentary
      increase in responding may be related to the reinforcement omission effect.

PMID- 16413143
TI  - Menstrual cycle phase and responses to drugs of abuse in humans.
AB  - Researchers have recently become aware of the importance of including women in
      research, including drug abuse research. With this increased awareness has come
      an increased scientific interest in the potential influence of menstrual cycle
      phase on responses to drugs. In this review, we discuss recent studies that have
      examined subjective and physiological responses to drugs of abuse in relation to
      menstrual cycle phase. With most of the drugs reviewed, including alcohol,
      benzodiazepines, caffeine, marijuana, nicotine and opioids, responses to the
      drugs were not different were inconsistent across cycle phases. However, with
      psychomotor stimulant drugs, such as amphetamine and cocaine, responses to the
      drugs were greater during the follicular, compared to the luteal, phase of the
      cycle. These findings suggest that, consistent with certain pre-clinical
      findings, circulating levels of ovarian hormones influence the central effects of
      stimulant drugs in women. With other drugs, the evidence to date suggests that
      ovarian hormones have modest, if any, effects on responses to abused drugs. We
      discuss methodological issues relating to inclusion of women with regular
      menstrual cycles.

PMID- 16413140
TI  - Effects of d-amphetamine on the behavior of pigeons exposed to the peak
      procedure.
AB  - The effects of d-amphetamine on pigeons' key-pecking under the peak interval (PI)
      procedure were investigated in two experiments. In experiment I the effects of
      doses of d-amphetamine from 0.75 to 3.0 mg/kg on responding under PI 30 and 45 s
      were studied for 10 successive days. Reductions in peak time and wait time were
      observed at both PI values and an increase in the width was found at PI 30 s.
      There was no evidence of tolerance. In experiment II, pigeons exposed to a PI 45
      s schedule were administered doses of D-amphetamine of 1.5 and 3.0 mg/kg for 30
      successive days. Reductions in peak time and wait time were found here. Evidence
      of tolerance was found in wait time, peak time and width of the distribution at
      the higher dose. In both experiments a rate-dependent effect of the drug was
      found in the portion of each peak trial before the time that food was delivered
      on reinforced trials; this effect was weaker after the customary time of food
      delivery. The rate-dependent effect for responses before food time, combined with
      little effect of the drug on responses after food time, is shown by simulation to
      be sufficient to account for the reduction in peak time, without the need to
      appeal to an internal clock mechanism.

PMID- 16413142
TI  - School-level contextual influences on smoking and drinking among Asian and
      Pacific Islander adolescents.
AB  - In this study, we seek to identify school contextual predictors of tobacco and
      alcohol use patterns (smoking only, drinking only, and both) among Asian and
      Pacific Islander (API) adolescents in California public schools and ethnic
      variation in determinants of substance use. The data included a sample of 26,692
      Asian and 3518 Pacific Islander (PI) adolescents from the 2000-2001 California
      Healthy Kids Survey. School-level information (n=836 schools) was from the
      California Basic Educational Data System and the 2000 census. Multilevel
      multinomial logistic regression was used to assess the association of school
      contexts with substance use patterns, controlling for individual-level factors.
      Pacific Islanders showed much higher prevalence of smoking and drinking than
      Asians, and the prevalence varied by school. School contexts were independently
      associated with API adolescents' substance use beyond the individual-level
      characteristics. The associations between school factors and outcomes also varied
      by ethnic group. Latino majority schools and schools with a high Asian immigrant
      concentration in the surrounding neighborhood had a lower risk of substance use
      among Asians but only to a modest degree among PIs. This study confirmed the
      importance of distinguishing Asians and PIs and the need for more attention to
      school contextual factors in adolescent substance use research.

PMID- 16413144
TI  - Self-administration of heroin, cocaine and their combination under a discrete
      trial schedule of reinforcement in rats.
AB  - Several self-administration models have been used to study the interactions
      between cocaine and heroin, and the schedule of reinforcement used is an
      important consideration for these studies. Behavior maintained by cocaine, heroin
      or their combination was studied using a discrete trial schedule that has been
      described for cocaine self-administration previously. This schedule permits 24 h
      access to drug without mortality associated with unlimited access to cocaine, and
      provides unique measures related to the circadian pattern of drug self
      administration. Cocaine and heroin combined maintained higher rates of responding
      compared to either drug alone when a maximum of three infusions were available
      each hour (DT3), and decreased food intake compared to cocaine alone. There were
      significantly greater numbers of hours in both the light and dark cycles during
      which animals self-administered heroin or the combination of cocaine/heroin
      compared to cocaine alone. When the FR was increased to 4 under the DT3 access
      conditions, responding maintained by cocaine or heroin extinguished to levels not
      different than those maintained by saline while food reinforcement remained
      intact. The combination of cocaine and heroin maintained robust responding under
      these conditions. This schedule of reinforcement appears to elucidate behavioral
      interactions between cocaine and heroin that are more complex than rate of drug
      consumption and may provide a procedure to address some of the issues related to
      co-abuse of these drugs.

PMID- 16413145
TI  - Intra-couple communication dynamics of HIV risk behavior among injecting drug
      users and their sexual partners in Northern Vietnam.
AB  - This paper elucidates the social context of HIV risk behavior and intra-couple
      risk communication among injecting drug users (IDUs) and their main sex partner.
      Data on shared injection equipment, unprotected sex with multiple partners,
      unprotected sex with a main partner and couples' dynamics and risk communication
      were gathered through separate in-depth interviews with 11 active male IDUs and
      11 of their primary female sex partners in Northern Vietnam. The majority of
      IDUs' sex partners does not inject drugs and is monogamous. In contrast, most
      IDUs reported a wide range of risky practices including needle sharing and
      unprotected sex with multiple, often concurrent, sex partners. Men rarely used
      condoms with primary partners. Many IDUs worried about their HIV-status, but none
      disclosed their injecting or sexual practices to their sex partners, leaving
      their partners unaware of their HIV risk. Among women who worried about HIV/AIDS,
      the vast majority was unable to influence their partner's needle sharing or
      extramarital affairs and most would not initiate condom use because they feared
      their partner's reaction. Couple-based interventions to facilitate risk
      communication combined with programs to promote condom use among male IDUs, may
      help to reduce HIV transmission from IDUs to their primary partners.

PMID- 16413146
TI  - Characteristics of U.S. substance abuse treatment facilities adopting
      buprenorphine in its initial stage of availability.
AB  - This study examined the adoption of buprenorphine for the treatment of opiate
      dependence among U.S. substance abuse treatment facilities and their
      characteristics at the time of the initial availability of the medication. Data
      come from a 2003 national survey of all substance abuse treatment facilities in
      the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they
      offered buprenorphine. Not unexpectedly, the prevalence was higher in certified
      opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid
      treatment programs, offering Naltrexone (OR=8.34, 95% CI=5.53, 12.58) and
      offering medically supervised withdrawal (OR=2.76, 95% CI=1.38, 5.52) were
      independent and robust predictors of offering buprenorphine. These same variables
      were independent predictors for the non-opioid treatment programs as well
      (Naltrexone, OR=14.32, 95% CI=7.85, 26.10; and medically supervised withdrawal
      services, OR=4.42, 95% CI=3.01, 6.49). Our results suggest that the adoption of
      buprenorphine soon after the Food and Drug Administration approved its use for
      treatment of opioid dependence and the shipping of the medication commenced was
      associated with facilities already offering pharmacotherapies such as Naltrexone
      and medically assisted withdrawal. These findings provide baseline data to track
      the adoption of buprenorphine by substance abuse treatment programs in future
      years.

PMID- 16413147
TI  - Risk factors for cocaine-induced paranoia in cocaine-dependent sibling pairs.
AB  - OBJECTIVE: Cocaine-induced paranoia (CIP), an irrational intense suspicion of
      others, is a common manifestation of cocaine dependence. Both environmental and
      genetic factors are thought to play a role, but the specific nature of such
      contributions is poorly understood. METHODS: Demographic, diagnostic, and cocaine
      use data were obtained from 420 cocaine-dependent, genetically confirmed, full
      sibling pairs (N=840 subjects) interviewed with the Semi-Structured Assessment
      for Drug Dependence and Alcoholism (SSADDA). Probands with and without CIP were
      compared; then, factors associated with sibling CIP status were analyzed by
      logistic regression. Alcohol dependence, a known heritable phenotype, was
      analyzed as a positive control. RESULTS: Of 420 probands, 273 (65%) experienced
      CIP. Probands with CIP were more severely dependent upon cocaine, had an earlier
      age of onset, were more likely to smoke cocaine, and used cocaine less frequently
      during the preceding year. Independent analyses of siblings replicated two of the
      former (i.e., dependence severity and age of onset). Probands with CIP also had a
      non-significantly higher proportion of siblings with the trait (66% versus 59%).
      Probands with concurrent alcohol dependence were confirmed to have significantly
      higher rates of alcoholism among their siblings. CONCLUSIONS: Severity of cocaine
      dependence and age of onset appear to be important risk factors for CIP.
      Concordance for CIP between siblings did not emerge as significant in our
      analyses.

PMID- 16413148
TI  - Comorbidity between alcohol dependence and illicit drug dependence in adolescents
      with antisocial behavior and matched controls.
AB  - BACKGROUND: Knowledge regarding the causes of comorbidity among substance use
      disorders can have significant impact on future research examining the etiology
      of these disorders. Unfortunately, the conclusions of past studies examining the
      comorbidity among substance use disorders are conflicting; some studies emphasize
      familial influences common to multiple substances, while others emphasize
      substance-specific influences. Discrepancies in results may reflect different
      analytical approaches or differences in the samples. Here, we examine the causes
      of comorbidity between alcohol dependence and illicit drug dependence in
      adolescents. METHODS: We ascertained a clinical sample of adolescents treated for
      antisocial behavior and substance use disorders and their siblings and a matched
      control sample. A model fitting approach was used to test 13 alternative
      hypotheses for the causes of comorbidity. RESULTS: The best supported hypothesis
      for the comorbidity between alcohol dependence and illicit drug dependence was a
      model hypothesizing that comorbid disorders are alternate forms of a single
      underlying liability. The next best fitting models were two of the correlated
      liabilities models (correlated risk factors and reciprocal causation).
      DISCUSSION: The results suggest that the best hypotheses explaining the
      comorbidity between alcohol and illicit drug dependence in adolescents are that
      alcohol dependence and illicit drug dependence are manifestations of a single
      general liability to develop substance dependence or that there are separate
      liabilities that are highly correlated.

PMID- 16413149
TI  - Plasmids in the aphid endosymbiont Buchnera aphidicola with the smallest genomes.
      A puzzling evolutionary story.
AB  - Buchnera aphidicola, the primary endosymbiont of aphids, has undergone important
      genomic and biochemical changes as an adaptation to intracellular life. The most
      important structural changes include a drastic genome reduction and the
      amplification of genes encoding key enzymes for the biosynthesis of amino acids
      by their translocation to plasmids. Molecular characterization through different
      aphid subfamilies has revealed that the genes involved in leucine and tryptophan
      biosynthesis show a variable fate, since they can be located on plasmids or on
      the chromosome in different lineages. This versatility contrasts with the genomic
      stasis found in three distantly related B. aphidicola strains already sequenced.
      We present the analysis of three B. aphidicola strains (BTg, BCt and BCc)
      belonging to aphids from different tribes of the subfamily Lachninae, that was
      estimated to harbour the bacteria with the smallest genomes. The presence of both
      leucine and tryptophan plasmids in BTg, a chimerical leucine-tryptophan plasmid
      in BCt, and only a leucine plasmid in BCc, indicates the existence of many
      recombination events in a recA minus bacterium. In addition, these B. aphidicola
      plasmids are the simplest described in this species, indicating that plasmids are
      also involved in the genome shrinkage process.

PMID- 16413154
TI  - Hepatocellular carcinoma: conventional MRI findings including gadolinium-enhanced
      dynamic imaging.
AB  - A great variety of MR pulse sequences for hepatocellular carcinomas (HCCs) are
      now available. In this article, we reviewed the current MR imaging techniques
      that are routinely used for hepatic imaging, and described the optimization of
      these sequences as well as the utility and characteristics of each sequence for
      the accurate diagnosis of HCCs. Then, we reviewed various MR imaging findings of
      advanced and early HCCs with emphasis on signal intensity and hemodynamic
      patterns. Finally, we described the value of multi-arterial-phase contrast
      enhanced dynamic MR imaging of the whole liver with excellent temporal resolution
      for evaluating transitional hemodynamics of hepatic lesions during the six
      arterial phases.

PMID- 16413159
TI  - Profiling of acylated homoserine lactones of Vibrio anguillarum in vitro and in
      vivo: Influence of growth conditions and serotype.
AB  - Vibrio anguillarum produces several interlinked acylated homoserine lactone (AHL)
      signal molecules which may influence expression of its virulence factors such as
      exoprotease production and biofilm formation. Using both thin layer
      chromatography and HPLC-high resolution mass spectrometry (HPLC-HRMS), we
      demonstrate in this study that the same types of AHLs are produced by many
      serotypes of V. anguillarum and that altering in vitro growth conditions
      (salinity, temperature and iron concentration) has little influence on the AHL
      profile. Most strains produced N-(3-oxodecanoyl)-l-homoserine lactone (3-oxo-C10
      HSL) and N-(3-hydroxy-hexanoyl)-l-homoserine lactone (3-hydroxy-C6-HSL) as the
      dominant molecules. Also, two spots with AHL activity appeared on TLC plates,
      which could not be identified as AHL structures. Trace amounts of N-(3-hydroxy
      octanoyl)-l-homoserine lactone, N-(3-hydroxy-decanoyl)-l-homoserine lactone and N
      (3-hydroxy-dodecanoyl)-l-homoserine lactone (3-hydroxy-C8-HSL, 3-hydroxy-C10-HSL
      and 3-oxo-C12-HSL, respectively) were also detected by HPLC-HRMS analysis from in
      vitro cultures. Most studies of quorum sensing (QS) systems have been conducted
      in vitro, the purpose of our study was to determine if the same acylated
      homoserine lactones were produced in vivo during infection. Extracts from
      infected fish were purified using several solid phase extraction strategies to
      allow chromatographic detection and separation by both TLC and HLPC-HRMS. 3-oxo
      C10-HSL and 3-hydroxy-C6-HSL were detected in organs from fish dying from
      vibriosis, however, compared to in vitro culturing where 3-oxo-C10-HSL is the
      dominant molecule, 3-hydroxy-C6-HSL was prominent in the infected fish tissues.
      Hence, the balance between the QS systems may be different during infection
      compared to in vitro cultures. For future studies of QS systems and the possible
      specific interference with expression of virulence factors, in vitro cultures
      should be optimised to reflect the in vivo situation.

PMID- 16413150
TI  - Data collection from very low birthweight infants in a geographical region:
      methods, costs, and trends in mortality, admission rates, and resource
      utilisation over a five-year period.
AB  - AIMS: 1. To determine the survival and morbidity of infants at discharge with a
      birthweight of less than 1500 g in the geographically defined population of East
      Anglia. 2. To demonstrate a cost-effective method of regional data collection. 3.
      To determine whether there were any changes in the demand for neonatal care.
      STUDY DESIGN AND SUBJECTS: A prospective cohort analysis using a single database
      to collect data on 1244 very low birthweight infants from eight neonatal units in
      one Region from 1993 to 1997. RESULTS: Estimated ascertainment of VLBW infants to
      the study was 96%. Over the 5 years survival rates were stable (75-79%). 52% of
      deaths in infants admitted for neonatal care occurred on day 1, with just 15% of
      deaths occurring after 28 days of life. Mortality risk significantly decreased
      with increasing gestational age at birth. Compared to 22-25-week old infants, the
      mortality risk decreased by 65% for 26-27-week old infants (OR 0.35 95% CI (0.21,
      0.59)) and by 92% for 32-39-week old infants (OR 0.08 95% CI (0.03, 0.21)) with
      intermediate odds ratios of 0.22 (0.12, 0.42) and 0.13 (0.06, 0.28) for the 28-29
      and 30-39 weeks gestation, respectively. Higher birthweight, after adjusting for
      gestation also decreased the mortality risk (OR 0.78 per 100 g difference, 95% CI
      (0.71, 0.86)). No change was seen in the number of extremely preterm infants
      admitted for intensive care or resource utilisation, although a significant
      increase was seen in the number of infants dying in delivery rooms. There was a
      reduction in the reported incidence of pulmonary interstitial emphysema (10-4%)
      but no change in the number of ventilation days or the rate of chronic lung
      disease. The mean maternal age increased from 27.7 years to 28.9 years during the
      study. Maternal steroid administration increased (30% to 59%) and was associated
      with a decreased risk of mortality (OR 0.44, 95% CI: 0.31-0.62). CONCLUSIONS: It
      is possible to collect useful data from the neonatal period at a reasonable cost
      from a geographically defined population. This information was used for informing
      clinicians, counselling parents and in the era of managed clinical networks will
      be useful in guiding the provision of effective health care resources.

PMID- 16413152
TI  - Reproductive characteristics of Rayini male goats of Kerman province in Iran.
AB  - An artificial vagina was used to collect semen from 14 native Iranian Rayini
      goats, at 15-day intervals starting on 1 July and ending on 30 December 2000.
      Testicular size, semen volume, sperm concentration, percent live sperm, percent
      normal sperm, and total number of live-normal sperm were significantly higher
      during the summer months. The average semen volume, percent live sperm and
      percent abnormal sperm during the sampling period varied between 1 and 1.4 mL, 60
      and 78%, and 7 and 13%, respectively. The total number of live and normal sperm
      in the ejaculate during the sampling period varied from 1000 to 2500 million.
      Testicular size, semen volume and the total number of live and normal sperm were
      significantly greater in bucks weighing 55-60 kg as compared with 50-54 kg.
      Seminal fluid pH values were significantly lower from July to October (pH <6)
      than the values from November to December (pH >6.1). Lowest level of lactate
      dehydrogenase in the seminal fluid was recorded in early September (2.2 U/mL) and
      the highest level in November (2.5 U/mL). Seminal fluid K ion level increased
      gradually from July (52 mg/dL) to the November (97 mg/dL). Variation of seminal
      fluid Na ion concentration (71-74 mg/dL) was not significant during the sampling
      period. The correlation coefficients of total number of live-normal sperm with
      seminal fluid K level (r=-0.65) and LDH (r=-0.36) were negative (P<0.01). The
      data indicated that the semen quality and quantity of Rayini bucks were higher
      during summer and early autumn.

PMID- 16413156
TI  - MRI of fetal acquired brain lesions.
AB  - Acquired fetal brain damage is suspected in cases of destruction of previously
      normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage
      may occur as a consequence of acute or chronic maternal diseases, with acute
      diseases causing impairment of oxygen delivery to the fetal brain, and chronic
      diseases interfering with normal, placental development. Infections, metabolic
      diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic
      events, iatrogenic accidents, and space-occupying lesions may also qualify as
      pathologic conditions that initiate intrauterine brain damage. MR manifestations
      of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can
      easily be recognized, as they are hardly different from postnatal lesions. The
      availability of diffusion-weighted sequences enhances the sensitivity in
      recognizing acute ischemic lesions. Recent hemorrhages are usually readily
      depicted on T2 (*) sequences, where they display hypointense signals. Chronic
      fetal brain injury may be characterized by nonspecific changes that must be
      attributable to the presence of an acquired cerebral pathology. The workup in
      suspected acquired fetal brain injury also includes the assessment of extra-CNS
      organs that may be affected by an underlying pathology. Finally, the placenta, as
      the organ that mediates oxygen delivery from the maternal circulation to the
      fetus, must be examined on MR images.

PMID- 16413151
TI  - Murine serum cytokines throughout the estrous cycle, pregnancy and post partum
      period.
AB  - Cytokines are pleiotropic glycoproteins participating in many aspects of
      mammalian reproductive physiology. Although murine models have been established
      to study normal and pathological pregnancy, the small volume of retrievable
      sample has hampered investigations into the role of cytokines in these processes.
      These problems were overcome by using fluid-phase multiplex immunoassays to
      monitor the serum profiles of 18 cytokines in single animals throughout normal
      murine reproduction: estrus, diestrus, post coitum, preimplantation,
      implantation, mid-pregnancy, late pregnancy and post partum. Most cytokines were
      detectable throughout all stages studied. Modest changes in profile were
      associated with estrous cyclicity and early pregnancy while virtually all
      cytokine levels increased markedly in mid- to late pregnancy and either fell
      slightly or levelled off post partum. The functional interrelationships between
      the various cytokines and the hormonal milieu are discussed with respect to
      gestational stage. Although certain profiles supported the 'conventional' Th1:Th2
      cytokine paradigm of pregnancy, many of the changes recorded were orchestrated
      around IL-12 (p40) and (p70). The present findings suggest that the traditional
      cytokine dichotomy poorly describes complex immunological processes like
      pregnancy.

PMID- 16413153
TI  - Properties of sustained release hot-melt extruded tablets containing chitosan and
      xanthan gum.
AB  - The aim of this study was to investigate the influence of pH, buffer species and
      ionic strength on the release mechanism of chlorpheniramine maleate (CPM) from
      matrix tablets containing chitosan and xanthan gum prepared by a hot-melt
      extrusion process. Drug release from hot-melt extruded (HME) tablets containing
      either chitosan or xanthan gum was pH and buffer species dependent and the
      release mechanisms were controlled by the solubility and ionic properties of the
      polymers. All directly compressed (DC) tablets prepared in this study also
      exhibited pH and buffer species dependent release. In contrast, the HME tablets
      containing both chitosan and xanthan gum exhibited pH and buffer species
      independent sustained release. When placed in 0.1N HCl, the HME tablets formed a
      hydrogel that functioned to retard drug release in subsequent pH 6.8 and 7.4
      phosphate buffers even when media contained high ionic strength, whereas tablets
      without chitosan did not form a hydrogel to retard drug release in 0.1N HCl. The
      HME tablets containing both chitosan and xanthan gum showed no significant change
      in drug release rate when stored at 40 degrees C for 1 month, 40 degrees C and
      75% relative humidity (40 degrees C/75% RH) for 1 month, and 60 degrees C for 15
      days.

PMID- 16413155
TI  - Transarterial embolization of primary and secondary tumors of the skeletal
      system.
AB  - Percutaneous transcatheteral embolizations of primary and secondary bone tumors
      are important minimal invasive angiographic interventions of the skeletal system.
      In most of the cases embolization is performed for preoperative devascularization
      or as a palliative measure to treat tumor-associated pain or other tumor bulk
      symptoms. The transarterial embolization of primary and secondary tumors of the
      skeletal system has been developed to a safe and very effective method.
      Indications, techniques, results and complications of this minimal invasive
      interventional therapy for treatment of primary and secondary bone tumors are
      described and discussed and compared with the newer literature and our own
      results.

PMID- 16413158
TI  - Molecular epidemiology of Vibrio nigripulchritudo, a pathogen of cultured penaeid
      shrimp (Litopenaeus stylirostris) in New Caledonia.
AB  - A collection of 57 isolates of Vibrio nigripulchritudo from either diseased or
      healthy shrimp and from shrimp farms environment was studied in order to gain a
      better understanding of the epidemiology of this pathogen, notably isolated from
      two distinct shrimp disease complexes. Molecular typing using two different
      techniques, arbitrarily primed PCR (AP-PCR) and multi-locus sequence typing
      (MLST), studied together with experimental pathology data allowed a relevant
      epidemiological insight into this possibly emerging pathogen. Additionally,
      results obtained with the two molecular typing techniques were congruent and
      allowed discriminating the strains associated with the "Summer Syndrome" from
      strains isolated from other contexts, especially the other shrimp vibriosis
      "Syndrome 93". These results highlight that the "Summer Syndrome" is most
      probably caused by an emergent clonal pathogen that therefore deserves
      surveillance and that AP-PCR can satisfactorily be used for that purpose.

PMID- 16413161
TI  - UPLC/MS for the identification of beta-blockers.
AB  - The beta-blockers Oxprenolol, Metoprolol, Acebutolol, Atenolol, Propranolol,
      Pindolol, and Alprenolol were analysed by both UPLC/MS and HPLC/MS using mobile
      phases containing acetonitrile, TFA and either H2O or D2O. UPLC gave superior
      separation performance and the quality of the mass spectra were at least as good
      as those from HPLC.

PMID- 16413160
TI  - Nitrogen-fixing sinorhizobia with Medicago laciniata constitute a novel biovar
      (bv. medicaginis) of S. meliloti.
AB  - Sixty-eight new rhizobial isolates were obtained from root-nodules of Medicago
      laciniata and from Mediterranean soils in Tunisia and France. All of them were
      identified as Sinorhizobium meliloti on the basis of PCR-RFLP analyses of 16S
      rDNA and the intergenic spacer sequence between 16S and 23S rDNAs. DNA/DNA
      hybridization, phenotypic characterization and 16S rRNA gene sequencing led to
      the conclusion that they belong the same taxon. All new isolates shared the
      ability to nodulate and fix nitrogen with M. laciniata except 11 of them not
      capable of fixing nitrogen with this plant and originating from French soils
      containing no efficiently adapted symbionts with M. laciniata. The nitrogen
      fixing rhizobia on M. laciniata differed markedly from the other S. meliloti or
      Sinorhizobium medicae isolates and references in their symbiotic traits such as
      nifDK RFLP diversity, nodA sequences and nitrogen effectiveness with tree other
      different annual Medicago species (M. truncatula, M. polymorpha and M. sauvagei).
      Two infrasubspecific (biovar) divisions are therefore proposed within S.
      meliloti: bv. medicaginis for Sinorhizobium efficient on M. laciniata and bv.
      meliloti for the classically known S. meliloti group represented by the strains
      ATCC9930(T) and RCR 2011 efficient on M. sativa.

PMID- 16413162
TI  - Adaptive responses and cellular behaviour of biphenyl-degrading bacteria toward
      polychlorinated biphenyls.
AB  - Polychlorinated biphenyls (PCBs) are one of the most widely distributed classes
      of chlorinated chemicals in the environment. For cleanup of large areas of PCB
      contaminated environments, bioremediation seems to be a promising approach.
      However, the multitude of PCB congeners, their low bioavailability and high
      toxicity are important factors that affect the cleanup progression. Elucidating
      how the PCB-degrading microorganisms involved in the process adapt to and deal
      with the stressing conditions caused by this class of compounds may help to
      improve the bioremediation process. Also specific physiological characteristics
      of biphenyl-utilizing bacteria involved in the degradation of PCBs may enhance
      their availability to these compounds and therefore contribute to a better
      microbial mineralization. This review will focus in the stress responses caused
      in aerobic biphenyl-utilizing bacteria by PCBs and its metabolic intermediates
      and will also analyze bacterial properties such as motility and chemotaxis,
      adherence to solid surfaces, biosurfactant production and biofilm development,
      all properties found to enhance bacteria-pollutant interaction.

PMID- 16413163
TI  - Model for mapping imprinted quantitative trait loci in an inbred F2 design.
AB  - The role of imprinting in shaping development has been ubiquitously observed in
      plants, animals, and humans. However, a statistical method that can detect and
      estimate the effects of imprinted quantitative trait loci (iQTL) over the genome
      has not been extensively developed. In this article, we propose a maximum
      likelihood approach for testing and estimating the imprinted effects of iQTL that
      contribute to variation in a quantitative trait. This approach, implemented with
      the EM algorithm, allows for a genome-wide scan for the existence of iQTL. This
      approach was used to reanalyze published data in an F(2) family derived from the
      LG/S and SM/S mouse strains. Several iQTL that regulate the growth of body weight
      by expressing paternally inherited alleles were identified. Our approach provides
      a standard procedure for testing the statistical significance of iQTL involved in
      the genetic control of complex traits.

PMID- 16413164
TI  - Evolutionary movement of centromeres in horse, donkey, and zebra.
AB  - Centromere repositioning (CR) is a recently discovered biological phenomenon
      consisting of the emergence of a new centromere along a chromosome and the
      inactivation of the old one. After a CR, the primary constriction and the
      centromeric function are localized in a new position while the order of physical
      markers on the chromosome remains unchanged. These events profoundly affect
      chromosomal architecture. Since horses, asses, and zebras, whose evolutionary
      divergence is relatively recent, show remarkable morphological similarity and
      capacity to interbreed despite their chromosomes differing considerably, we
      investigated the role of CR in the karyotype evolution of the genus Equus. Using
      appropriate panels of BAC clones in FISH experiments, we compared the centromere
      position and marker order arrangement among orthologous chromosomes of
      Burchelli's zebra (Equus burchelli), donkey (Equus asinus), and horse (Equus
      caballus). Surprisingly, at least eight CRs took place during the evolution of
      this genus. Even more surprisingly, five cases of CR have occurred in the donkey
      after its divergence from zebra, that is, in a very short evolutionary time
      (approximately 1 million years). These findings suggest that in some species the
      CR phenomenon could have played an important role in karyotype shaping, with
      potential consequences on population dynamics and speciation.

PMID- 16413165
TI  - Genome analysis of Escherichia coli promoter sequences evidences that DNA static
      curvature plays a more important role in gene transcription than has previously
      been anticipated.
AB  - We have performed a computer analysis to study the prevalence of DNA static
      curvature in the regulatory regions of Escherichia coli, detecting a large number
      of operons with curved DNA fragments in their 5' upstream regions. A statistical
      analysis reveals that all the global transcription factors identified so far in
      E. coli have a tendency to regulate operons with curved DNA sequences in their
      upstream regions. In addition to these global regulators, we also found that the
      PurR, ArgR, FruR, TyrR, and CytR specific regulators present a similar
      propensity. Interestingly, for these cases we found no previous reference
      describing a possible relationship with curved DNA regions. To validate our
      theoretical results, we performed site-directed mutagenesis to reduce the degree
      of DNA curvature in the regulatory sequences of the aroG, pyrC, and argCBH
      operons. The effects of these changes were measured by polyacrylamide gel
      electrophoresis assays and further evaluated in vivo by transcriptional fusions
      to a reporter gene. All our results point toward a more widespread role of curved
      DNA in gene transcription, a fact that has previously been underestimated.

PMID- 16413166
TI  - Quality prediction of cell substrate using gene expression profiling.
AB  - Changes in cell culture conditions influence the metabolism of cells, which
      consequently affects the quality of the products that they produce, such as viral
      vectors, recombinant proteins, or vaccines. Currently there is no effective
      technique available to monitor global quality of cells in cell culture. Here we
      describe a new method using gene expression profiling by microarray to predict
      the quality of cell substrates. Human embryonic kidney 293 cells are a commonly
      used cell substrate in the production of biological products. We demonstrate that
      the yield of adenoviral vectors was lower in over-confluent 293 cells, compared
      to 40 or 90% confluent cells. Total RNA derived from these cells of different
      confluence states was reverse transcribed, labeled, and used to hybridize 10K
      cDNA arrays to determine biomarkers for confluence states. Phenotype scatter-plot
      analysis and cluster analysis were used for class discovery. Based on this
      approach, we identified genes that were either up-regulated or down-modulated in
      response to different cell confluence states. By multivariate predictive models
      we identified a set of 37 genes that were either down-regulated or up-regulated
      compared to 90% confluent cells as a predictor of cell confluence and quality of
      293 cell cultures. The predictive accuracy of these models was assessed by the
      leave-one-out cross-validation method. The expression of selected gene predictors
      was validated by quantitative PCR analysis. Our results demonstrate that gene
      expression profiling can assess the quality of cell substrates prior to large
      scale production of a biological product.

PMID- 16413167
TI  - The first radiation hybrid map of a perch-like fish: the gilthead seabream
      (Sparus aurata L).
AB  - Among Teleosts, Perciformes are the largest order of fishes and include numerous
      species of commercial importance. Perciformes also comprise species of primary
      interest for evolutionary studies and analysis of the sex determination systems
      and sex chromosome plasticity. Unfortunately, genomics tools and resources for
      Perciformes remain to be developed. Here, we report the production of a seabream
      whole-genome radiation hybrid (RH) panel in which quality was ascertained by the
      construction of a 2-Mb-resolution RH map. The map encompasses 440 markers (288
      microsatellites, 82 gene-based markers, and 70 STS) suitable for linkage analysis
      and comparative mapping studies. Achievement of a RH panel and a whole-genome RH
      map should contribute to establishing seabream as a fish model among the
      Perciformes and should be of importance in aquaculture for marker-assisted
      selection, improvement of growth performance, and disease management. Development
      of RH maps in a cost-effective manner for other fishes with the described
      methodology will offer a powerful approach in aquaculture and will provide
      extended capabilities for comparing vertebrate genome evolution.

PMID- 16413168
TI  - Sjogren's syndrome in the NOD mouse model is an interleukin-4 time-dependent,
      antibody isotype-specific autoimmune disease.
AB  - NOD.B10-H2b and NOD/LtJ mice manifest many features of primary and secondary
      Sjogren's syndrome (SjS), respectively, an autoimmune disease affecting primarily
      the salivary and lacrimal glands leading to xerostomia (dry mouth) and
      xerophthalmia (dry eyes). A previous study suggested that the T(H2) cytokine,
      interleukin (IL)-4, plays an integral role in the development and onset of SjS
      like disease in the NOD mouse model. To define further the role of IL-4 in onset
      of murine SjS-like disease, we have examined two IL4 gene knockout (KO) mouse
      strains, NOD.IL4-/- and NOD.B10-H2b.IL4-/-. Unlike NOD.IL4-/- mice, NOD.B10
      H2b.IL4-/- mice are resistant to development of diabetes. The presence of a
      dysfunctional IL4 gene did not impede leukocyte infiltration of the salivary
      glands, yet prevented development of secretory dysfunction. Whereas NOD.B10
      H2b.IL4-/- mice exhibited many pathophysiological manifestations of SjS-like
      disease common to the parental strains, these mice failed to produce anti
      muscarinic acetylcholine type-3 receptor (M3R) autoantibodies of the IgG1
      isotype. Cytokine mRNA expression profiles and adoptive transfers of T
      lymphocytes from NOD.B10-H2b.Gfp mice into NOD.B10-H2b.IL4-/- mice at different
      ages suggest IL-4 is required during the pre-clinical disease stage (around 12
      weeks of age) to initiate clinical xerostomia. The results of this study indicate
      that the failure of NOD.IL4-/- and NOD.B10-H2b.IL4-/- mice to synthesize anti-M3R
      autoantibodies of the IgG1 isotype apparently explains why these mice fail to
      develop exocrine gland dysfunction, despite exhibiting pre-clinical
      manifestations of SjS-like disease.

PMID- 16413169
TI  - Receptor-type PTP-NP inhibition of Dynamin-1 GTPase activity is associated with
      neuronal depolarization.
AB  - Dynamin-1 is a GTP-hydrolyzing protein and a key element in the clathrin-mediated
      endocytosis of secretory granules and neurovesicles at the plasma membrane. The
      unique receptor-like protein tyrosine phosphatase, PTP-NP/Phogrin/IAR/IA-2, is
      associated with neuroendocrine secretory granules and is highly expressed in the
      brain. Here, we show by confocal microscopy and biochemical studies that PTP-NP
      rapidly associates with Dynamin-1 in a depolarization-dependent manner and
      regulates Dynamin-1 GTPase activity upon KCl depolarization of rat primary
      hippocampal neurons. Depolarization of primary neurons induced direct association
      of PTP-NP with Dynamin-1 within 30 s. This association resulted in significant
      inhibition of Dynamin-1 GTPase activity (approximately 75% inhibition). Mutation
      within the phosphatase domain of PTP-NP (PTP-NP(D947A)) abolished the direct
      interaction of PTP-NP with Dynamin-1 and failed to inhibit Dynamin-1 GTPase
      activity. To further confirm the endogenous interaction of Dynamin-1 with wild
      type PTP-NP, Dynamin-1 was purified biochemically from rat brain and its
      interaction with purified PTP-NP was analyzed. Highly purified Dynamin-1
      specifically associated with wild-type PTP-NP and not with mutated PTP-NP,
      resulting in significant inhibition (approximately 70%) of Dynamin-1 GTPase
      activity. This is the first report to suggest a novel function of this unique
      receptor-type tyrosine phosphatase as a potential regulator of Dynamin-1 GTPase
      activity upon neuronal depolarization.

PMID- 16413170
TI  - Introduction to zonisamide.
AB  - Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved recently in
      Europe as adjunctive therapy for refractory partial seizures in adults, has been
      used extensively in Japan and the United States. A substantial body of clinical
      experience has accumulated over a 14-year period, allowing the properties and
      pharmacologic/clinical profiles of zonisamide to be clearly defined. Zonisamide
      is structurally distinct from other AEDs and has multiple and complementary
      mechanisms of action, which likely contribute to its efficacy across a broad
      range of epilepsy types. Zonisamide has a long T1/2 enabling once-daily dosing,
      linear pharmacokinetics and minimal interaction with other drugs; plasma levels
      of commonly administered AEDs and oral contraceptives are unaffected by
      concomitant zonisamide. Effective control of partial seizures (up to 51% decrease
      in seizure frequency) is attained at doses of >or=300 mg/day, and optimal
      titration and maintenance dosing schedules have been established. The adverse
      event profile is well defined; in common with most AEDs, most adverse events are
      central nervous system-related (e.g. somnolence, dizziness, tiredness). Adverse
      events may be minimised with appropriate patient management. Zonisamide therefore
      has many characteristics considered desirable in an AED and represents a valuable
      addition to the therapeutic options for treating epilepsy in Europe.

PMID- 16413171
TI  - Outcomes research: clinical trials in the elderly.
AB  - Very few clinical trials have been done in the elderly. This report reviews
      results of two completed studies and describes one in progress. The largest
      published study was a United States Veterans Affairs Administration study in
      newly diagnosed patients with epilepsy. It compared carbamazepine to gabapentin
      and lamotrigine, and found that, although equivalent in efficacy, the newer
      antiepileptic drugs (AEDs) were better tolerated. This study also highlighted
      many of the difficulties in recruiting and retaining elderly patients in studies,
      the large number of comorbidities, and the problems of distinguishing seizures in
      the elderly from other symptoms. Another study of new-onset epilepsy suggested
      that a large percentage of elderly patients respond to initial AED therapy, but
      side effect profiles differ. More studies are needed to better define the
      risk/benefit relationships in elderly patients.

PMID- 16413172
TI  - Dopaminergic-based pharmacotherapies for depression.
AB  - The serendipitous discovery of the precursors of two of the major contemporary
      antidepressant families during the late 1950s, iproniazid for the monoamine
      oxidase inhibitors (MAOIs) and imipramine for the tricyclic antidepressants
      (TCAs), has guided the subsequent development of antidepressant compounds with
      predominantly serotonergic, noradrenergic or combined serotonergic and
      noradrenergic activity. Unfortunately, however, many depressed patients continue
      to remain symptomatic despite adequate treatment with pharmacologic agents
      currently available. When one reviews the list of pharmacologic agents currently
      approved for the treatment of Major Depressive Disorder (MDD), it is apparent
      that relatively few treatments with dopaminergic activity have been developed to
      date. Therefore, developing effective antidepressant treatments with pro
      dopaminergic properties which also possess a relatively wide safety margin may
      further improve the standard of care for depression. In the present article we
      will briefly review studies focusing on the role of dopamine in depression
      followed by a comprehensive review of pharmacotherapies for depression with pro
      dopaminergic activity.

PMID- 16413173
TI  - From selective to highly selective SSRIs: a comparison of the antinociceptive
      properties of fluoxetine, fluvoxamine, citalopram and escitalopram.
AB  - Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess
      secondary binding properties, while citalopram and its S-enantiomer
      (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of
      acute pain hotplate analgesia meter, we evaluated the antinociceptive properties
      of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p.
      Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50)
      value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a
      weak antinociceptive effect with an inverse "U" shape curve. All three drug's
      effects were not abolished by naloxone. Escitalopram did not elicit any effect at
      quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and
      citalopram given i.p. are weak antinociceptors, (not mediated through opioid
      mechanisms), while escitalopram possesses no antinociceptive properties when
      injected i.p. This difference between citalopram and escitalopram calls for
      further studies in order to assess the various differences between the two
      enantiomers of citalopram, and between each enantiomer and the racemic mixture.

PMID- 16413175
TI  - Highly efficient transgenesis in Xenopus tropicalis using I-SceI meganuclease.
AB  - In this study, we report a highly efficient transgenesis technique for Xenopus
      tropicalis based on a method described first for Medaka. This simple procedure
      entails co-injection of meganuclease I-SceI and a transgene construct flanked by
      two I-SceI sites into fertilized eggs. Approximately 30% of injected embryos
      express transgenes in a promoter-dependent manner. About 1/3 of such embryos show
      incorporation of the transgene at the one-cell stage and the remainder are 'half
      transgenics' suggesting incorporation at the two-cell stage. Transgenes from both
      classes of embryos are shown to be transmitted and expressed in offspring. The
      procedure also works efficiently in Xenopus laevis. Because the needle injection
      procedure does not significantly damage embryos, a high fraction develop normally
      and can, as well, be injected with a second reagent, for example an mRNA or
      antisense morpholino oligonucleotide, thus allowing one to perform several
      genetic manipulations on embryos at one time. This simple and efficient technique
      will be a powerful tool for high-throughput transgenesis assays in founder
      animals, and for facilitating genetic studies in the fast-breeding diploid frog,
      X. tropicalis.

PMID- 16413174
TI  - A yeast-based model of alpha-synucleinopathy identifies compounds with
      therapeutic potential.
AB  - We have developed a yeast-based model recapitulating neurotoxicity of alpha
      synuclein fibrilization. This model recognized metal ions, known risk factors of
      alpha-synucleinopathy, as stimulators of alpha-synuclein aggregation and
      cytotoxicity. Elimination of Yca1 caspase activity augmented both cytotoxicity
      and inclusion body formation, suggesting the involvement of apoptotic pathway
      components in toxic alpha-synuclein amyloidogenesis. Deletion of hydrophobic
      amino acids at positions 66-74 in alpha-synuclein reduced its cytotoxicity but,
      remarkably, did not lower the levels of insoluble alpha-synuclein, indicating
      that noxious alpha-synuclein species are different from insoluble aggregates. A
      compound screen aimed at finding molecules with therapeutic potential identified
      flavonoids with strong activity to restrain alpha-synuclein toxicity. Subsequent
      structure-activity analysis elucidated that these acted by virtue of anti-oxidant
      and metal-chelating activities. In conclusion, this yeast-cell model as presented
      allows not only fundamental studies related to mechanisms of alpha-synuclein
      instigated cellular degeneration, but is also a valid high-throughput
      identification tool for novel neuroprotective agents.

PMID- 16413176
TI  - Convergent Wnt and FGF signaling at the gastrula stage induce the formation of
      the isthmic organizer.
AB  - The development of the vertebrate brain depends on the formation of local
      organizing centres within the neural tube that express secreted signals that
      refine local neural progenitor identity. The isthmic organizer (IsO) forms at the
      isthmic constriction and is required for the growth and ordered development of
      mesencephalic and metencephalic structures. The formation of the IsO, which is
      characterized by the generation of a complex pattern of cells at the midbrain
      hindbrain boundary, has been described in detail. However, when neural plate
      cells are initially instructed to form the IsO, the molecular nature of the
      inductive signals remain poorly defined. We now provide evidence that convergent
      Wnt and FGF signaling at the gastrula stage are required to generate the complex
      polarized pattern of cells characteristic of the IsO, and that Wnt and FGF
      signals in combination are sufficient to reconstruct, in naive forebrain cells,
      an IsO-like structure that exhibits an organizing activity that mimics the
      endogenous IsO when transplanted into the diencephalon of chick embryos.

PMID- 16413177
TI  - Release behaviors of porous poly(butylene succinate)/poly(epsilon-caprolactone)
      microcapsules containing indomethacin.
AB  - The biodegradable poly(butylene succinate)/poly(epsilon-caprolactone) (PBS/PCL)
      microcapsules containing indomethacin were prepared by emulsion solvent
      evaporation method. The morphologies, thermal properties, and release behaviors
      of PBS/PCL microcapsules were investigated. As a result, the microcapsules
      exhibited porous and spherical form in the presence of gelatin as a surfactant.
      From the DSC result, the PBS/PCL microcapsules showed the two exothermic peaks
      meaning the melting points of PCL and PBS. The results of FT-IR and DSC proved
      that the PBS and PCL were mixed so that the PBS/PCL microcapsules were composed
      of two wall-forming materials. And the release rate of indomethacin from the
      microcapsules was decreased with increasing the PCL content. It was noted that an
      addition of PCL on the PBS led to the decrease of pore size in the PBS/PCL
      microcapsules.

PMID- 16413178
TI  - Ligand-binding specificities of laminin-binding integrins: a comprehensive survey
      of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1,
      alpha7beta1 and alpha6beta4 integrins.
AB  - The interactions of cells with basement membranes are primarily mediated via the
      engagement of laminins by a group of integrin family proteins, including
      integrins alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4. To explore the
      ligand-binding specificities of these laminin-binding integrins, we produced
      these integrins, including two alpha7beta1 splice variants (alpha7X1beta1 and
      alpha7X2beta1), as soluble recombinant proteins and determined their binding
      specificities and affinities toward a panel of purified laminin isoforms
      containing distinct alpha chains. Among the five laminin-binding integrins
      investigated, alpha3beta1 and alpha6beta4 exhibited a clear specificity for
      laminin-332 (alpha3beta3gamma2) and laminin-511 (alpha5beta1gamma1)/521
      (alpha5beta2gamma1), while integrin alpha6beta1 showed a broad specificity,
      binding to all laminin isoforms with a preference for laminin-111
      (alpha1beta1gamma1), laminin-332 and laminin-511/521. The two alpha7beta1
      variants were distinct from alpha3beta1, alpha6beta1 and alpha6beta4 in that they
      did not bind to laminin-332. alpha7X1beta1 bound to all laminins, except laminin
      332, with a preference for laminin-211 (alpha2beta1gamma1)/221
      (alpha2beta2gamma1) and laminin-511/521, while alpha7X2beta1 bound preferentially
      to laminin-111 and laminin-211/221. Laminin-511/521 was the most preferred ligand
      for all the laminin-binding integrins, except for alpha7X2beta1, whereas laminin
      411 was the poorest ligand, capable of binding to alpha6beta1 and alpha7X1beta1
      with only modest binding affinities. These comprehensive analyses of the
      interactions between laminin-binding integrins and a panel of laminins clearly
      demonstrate that the isoforms of both integrins and laminins differ in their
      binding specificities and affinities, and provide a molecular basis for better
      understanding of the adhesive interactions of cells with basement membranes of
      defined laminin compositions.

PMID- 16413179
TI  - Rhinitis and snoring as risk factors for hypertension in post-menopausal women.
AB  - OBJECTIVE: Several studies have suggested an association between snoring and
      hypertension. An association between rhinitis and hypertension has been recently
      indicated in men but not in women. Since menopausal status is an important
      determinant of blood pressure, we evaluated the relationship between rhinitis,
      snoring and blood pressure taking into account the modifying effect of menopausal
      status. DESIGN: Cross-sectional survey. SETTINGS: Four areas of Italy: the Po
      river Delta, Pisa (Tuscany), Viterbo (Lazio) and Rome. MAIN OUTCOME MEASURES:
      Data were collected by a questionnaire and a medical visit. PARTICIPANTS: One
      thousand five hundred and fifty-four female non-smokers. RESULTS: Systolic blood
      pressure (SBP) was significantly related to both occasional and habitual snoring
      in the overall sample. No associations were found between SBP, snoring, and
      rhinitis in pre-menopausal women. Both occasional and habitual snoring, but not
      rhinitis, were significant risk factors for increased SBP in women who stopped
      menstruating fewer than 11 years previously (beta=10.27 mmHg, 95% confidence
      interval (CI)=3.5, 17.01 and beta=9.91 mmHg, 95% CI=2.3, 17.5, respectively).
      However, women who had been menopausal for more than 11 years were found to have
      an increased SBP if they were occasional snorers (beta=8.94 mmHg 95% CI=1.2,
      16.6) or habitual snorers (beta=8.01 mmHg, 95% CI=0.10, 15.9). The increase in
      SBP was even greater in these women when habitual snoring was associated with
      rhinitis (beta=11.96 mmHg, 95% CI=1.01, 22.9). CONCLUSION: We suggest that the
      association of snoring with rhinitis may facilitate the development of apnea
      during sleep, which in post-menopausal women may increase the risk of developing
      hypertension.

PMID- 16413180
TI  - Effect of culture conditions on fatty acids composition of a biosurfactant
      produced by Candida ingens and changes of surface tension of culture media.
AB  - This work investigated the effect of culture medium composition on a
      biosurfactant production and their total fatty acids content, as well as the
      surface tension of media, and biomass production by Candida ingens. A factorial
      experimental design was used to evaluate the combined effect of C/P,
      C/N(inorganic), C/Fe, C/Mg ratios and yeast extract concentration. The highest
      biosurfactant production was reached when high C/Fe and high C/P ratio variables
      were combined; biosurfactant concentration increased by a 3.42 fold. The variable
      with the highest effect on net decrease surface tension (DeltaST) and fatty acids
      percentage of C. ingens biosurfactant was yeast extract. The average of DeltaST
      (25 mN/m) and fatty acids percentage (34.7%) values were enhanced at high yeast
      extract concentration of 1g/l. The main conclusion of this study was that the
      culture composition affected the biosurfactant production by C. ingens. It was
      also observed that the surface tension and total fatty acids of the biosurfactant
      were modified as the media composition changed.

PMID- 16413181
TI  - Pure human urine is a good fertiliser for cucumbers.
AB  - Human urine obtained from separating toilets was tested as a fertiliser for
      cultivation of outdoor cucumber (Cucumis sativus L.) in a Nordic climate. The
      urine used contained high amounts of nitrogen with some phosphorus and potassium,
      but numbers of enteric microorganisms were low even though urine had not been
      preserved before sampling. The cucumber yield after urine fertilisation was
      similar or slightly better than the yield obtained from control rows fertilised
      with commercial mineral fertiliser. None of the cucumbers contained any enteric
      microorganisms (coliforms, enterococci, coliphages and clostridia). In the taste
      assessment, 11 out of 20 persons could recognise which cucumber of three
      cucumbers was different but they did not prefer one over the other cucumber
      samples, since all of them were assessed as equally good.

PMID- 16413182
TI  - Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza
      bicyclo[2.2.1]heptane-3-carboxylic acid.
AB  - Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver
      and hepatocellular carcinoma. The etiological agent HCV virus codes a single
      polyprotein of approximately 3000 amino acids that is processed with the help of
      a serine protease NS3A to produce structural and non-structural proteins required
      for viral replication. Inhibition of NS3 protease can potentially be used to
      develop drugs for treatment of HCV infections. Herein, we report the development
      of a series of novel NS3 serine protease inhibitors derived from 2-aza
      bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for
      treatment of HCV infections.

PMID- 16413183
TI  - Small molecule inhibitors of plasma kallikrein.
AB  - Plasma kallikrein is a serine protease that is involved in pathways of
      inflammation, complement fixation, coagulation, and fibrinolysis. Herein, we
      describe the SAR and structural binding modes of a series of inhibitors of plasma
      kallikrein as well as the pharmacokinetics of a lead analog 11 in rat.

PMID- 16413184
TI  - Schiff base conjugates of p-aminosalicylic acid as antimycobacterial agents.
AB  - Schiff base conjugates of p-aminosalicylic acid have been synthesized and
      characterized by elemental analysis, IR and (1)H NMR spectroscopy and cyclic
      voltammetry. Compounds containing hydroxyl-rich side chains show enhanced
      antimycobacterial activity against Mycobacterium smegmatis and Mycobacterium
      bovis BCG. Higher ClogP values and superior radical scavenging activities are
      thought to be the contributing factors for their enhanced antimycobacterial
      activities.

PMID- 16413185
TI  - In silico identification of novel EGFR inhibitors with antiproliferative activity
      against cancer cells.
AB  - Inhibition of the epidermal growth factor receptor (EGFR) tyrosine kinase
      activity by small molecules has proved effective for the treatment of cancer. To
      the best of our knowledge, the crystal structure of EGFR has been used for the
      first time to identify novel inhibitor chemotypes by docking-based in silico
      screening of a large virtual chemical library followed up by experimental
      validation. We identified several compounds with antiproliferative effects on
      cancer cells. Amongst them, a C(4)-N(1)-substituted pyrazolo[3,4-d]pyrimidine MSK
      039 (39) was discovered as a low-micromolar inhibitor of EGFR tyrosine kinase
      activity. The predicted binding mode of 39 opens a new avenue toward the
      optimization of novel chemical entities to develop potent and selective
      inhibitors of EGFR signaling.

PMID- 16413186
TI  - A series of 23,24-dihydrodiscodermolide analogues with simplified lactone
      regions.
AB  - A collection of seven new 23,24-dihydrodiscodermolide analogues have been
      synthesized with modifications to the lactone ring, some of which show
      antiproliferative activities similar to discodermolide.

PMID- 16413187
TI  - What is the purpose of cancer staging?

PMID- 16413188
TI  - Changes in muscle activity in children with hemiplegic cerebral palsy while
      walking with and without ankle-foot orthoses.
AB  - We compared the electromyographic (EMG) signals of lower extremity muscle groups
      in 10 children with hemiplegic cerebral palsy (CP) while walking barefoot and in
      a hinged ankle-foot orthosis (HAFO). All children had excessive plantarflexion
      and initial toe-contact on the affected side when walking barefoot, a typical
      gait pattern for hemiplegic patients. The patients walked with a physiological
      heel-toe gait pattern when wearing the HAFO. The peak activity of the tibialis
      anterior muscle was reduced by 36.1% at initial contact and loading response
      phase and by 57.3% just after toe-off when using a HAFO. The decrease in activity
      was thought to result from the change in gait pattern from a toe-gait to a heel
      toe gait as well as the use of a HAFO. The HAFO also slightly decreased muscle
      activity in the proximal leg muscles mainly during swing phase, improved stride
      length, decreased cadence, improved walking speed, increased peak hip flexion,
      improved kinematics in loading response phase at the knee, and reduced the
      excessive ankle plantarflexion.

PMID- 16413189
TI  - A novel method of producing a repetitive dynamic signal to examine reliability
      and validity of gait analysis systems.
AB  - Gait dysfunction is a common functional complaint of clients who seek medical
      care. Gait dysfunction can be caused by musculoskeletal disorders such as
      osteoarthritis or fractures, or it can be caused by neuromuscular disorders such
      as multiple sclerosis or cerebrovascular accident. Decisions made by health care
      providers working with these clients could be enhanced by the availability of
      valid and reliable gait measurement. Valid and reliable gait measurement is
      possible with laboratory-based motion analysis systems, but these are not
      universally available. Several portable systems collect footfall data and provide
      a relatively inexpensive alternative to sophisticated motion analysis systems.
      However, data collected by these portable systems cannot be used with confidence
      because of the lack of verification of the validity and reliability of the data
      they collect about movement. This paper describes a novel method of examining
      test-retest reliability and concurrent validity that produces a signal with
      minimal variation. To produce repetitive distance and timing events, a
      cylindrical weight was rolled across the field of both the laboratory motion
      analysis system and the system to be evaluated. Measures of the weight's movement
      were taken simultaneously with both systems. A reference point was chosen to
      allow for comparison between the systems. The spatial measure that was compared
      between systems was the horizontal distance between successive repetitions of the
      reference point's vertical position. The temporal measure that was compared
      between systems was the time between successive repetitions of the reference
      point's vertical position. The method described in this paper provides a
      minimally variable repetitive signal that can be used to investigate concurrent
      validity of gait analysis systems.

PMID- 16413190
TI  - Building the invisible wall: updating the chlamydial peptidoglycan anomaly.
AB  - The existence of peptidoglycan (PG) in chlamydiae has long been debated. Genome
      sequencing of members of the Chlamydiaceae family and Protochlamydia amoebophila
      has uncovered a nearly complete pathway for PG synthesis in these organisms. The
      recent use of microarray and proteomic analysis methods has revealed that PG
      synthesis genes are expressed primarily during reticulate body development and
      division. Furthermore, key genes in the chlamydial PG synthesis pathway encode
      functional PG synthesis enzymes, some of which provide the basis for the
      susceptibility of chlamydiae to PG inhibitors. Recent studies shed light on how
      the construction of a cell wall in chlamydiae is taking shape and why the wall is
      being built.

PMID- 16413192
TI  - 2,4-Dimethoxyphenylsemicarbazones with anticonvulsant activity against three
      animal models of seizures: synthesis and pharmacological evaluation.
AB  - Various 2,4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4
      dimethoxyaniline via a phenylcarbamate intermediate. The structures were
      confirmed by spectral and elemental analyses. The anticonvulsant activity of the
      synthesized compounds was established after intraperitoneal administration in
      three seizure models in mice which include maximal electroshock seizure,
      subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure
      screens. Nine compounds exhibited protection in all the three seizure models, and
      N1-(2,4-dimethoxyphenyl)-N4-(propan-2-one)semicarbazone (17) emerged as the most
      active compound with no neurotoxicity. These compounds were found to elevate
      gamma-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata
      regions equipotent to clobazam.

PMID- 16413191
TI  - Ancient lateral gene transfer in the evolution of Bdellovibrio bacteriovorus.
AB  - The recently sequenced genome of the predatory delta-proteobacterium Bdellovibrio
      bacteriovorus provides many insights into its metabolism and evolution. Because
      its genes are reasonably uniform in G+C content, it was suggested that B.
      bacteriovorus actively resists recombination with foreign DNA and horizontal
      transfer of DNA from other bacteria. To investigate this further, we carried out
      a variety of phylogenetic and comparative genomics analyses using data from >200
      microbial genomes, including several published delta-proteobacteria. Although
      there might be little evidence for the extensive recent transfer of genes, we
      demonstrate that ancient lateral gene acquisition has shaped the B. bacteriovorus
      genome to a great extent.

PMID- 16413193
TI  - Synthesis and DNA cleavage reaction characteristics of enediyne prodrugs
      activated via an allylic rearrangement by base or UV irradiation.
AB  - A number of enediyne prodrugs 1-5 possessing an (E)-3-hydroxy-4-(2'-hydroxy-1'
      phenylethylidene)cyclodeca-1,5-diyne scaffold have been synthesized via the
      Sonogashira coupling and an intramolecular Nozaki-Hiyama-Kishi reaction as the
      key steps. Upon incubation with enediyne prodrugs 4 and 5 possessing a free
      hydroxymethyl group on the exocyclic double bond, circular supercoiled DNA (Form
      I) underwent single strand cleavage into circular relaxed DNA (Form II) in buffer
      solution at pH 8.5, while the silylated analogs 1-3 showed very weak DNA cleavage
      activity. Alternatively, the silylated analogs 1-3 could be activated by UV
      irradiation via a photochemical alkene isomerization followed by an allylic
      rearrangement to form the putative epoxy enediyne, resulting in efficient DNA
      cleavage similar to the level observed with the prodrugs 4 and 5.

PMID- 16413194
TI  - Soil radon monitoring in the NE flank of Mt. Etna (Sicily).
AB  - Soil radon has been monitored at a fixed location on the northeastern flank of
      Mt. Etna, a high-risk volcano in Sicily. The aim of this study was to evaluate
      the effects of the recent volcanic activity on soil radon concentration.
      Continuous radon measurements have been performed since July 2001. While
      comparison between the trend in in-soil radon concentration and the acquired
      meteorological series (temperature, humidity and pressure) appear to confirm a
      general seasonal correlation, nevertheless particular anomalies suggest a
      possible dependence of the radon concentration on volcanic dynamics.

PMID- 16413195
TI  - Bioluminescence and exogenous compounds: physico-chemical basis for
      bioluminescent assay.
AB  - Bioluminescent systems are convenient objects to study mechanisms of influence of
      exogenous molecules on living organisms. Classification of physical and physico
      chemical mechanisms of the effects of luminous bacteria Photobacterium leiognathi
      on bioluminescent reactions is suggested. Five mechanisms are discussed: (1)
      change of electron-excited states' population and energy transfer, (2) change of
      efficiency of S-T conversion in the presence of external heavy atom, (3) change
      of rates of coupled reactions, (4) interactions with enzymes and variation of
      enzymatic activity, (5) nonspecific effects of electron acceptors. Effects of
      various groups of chemical compounds are discussed according to the
      classification suggested. The compounds are: a series of fluorescent dyes,
      organic oxidizers, organic and inorganic heavy-atom containing compounds, and
      metallic salts. Applications of fluorescence time-resolved and steady-state
      techniques, as well as bioluminescence kinetics study, are discussed. The
      patterns of exogenous compounds' influence form a physico-chemical basis for
      bioluminescent ecological assay.

PMID- 16413196
TI  - Photosensitization of different Candida species by low power laser light.
AB  - The aim of this study was to evaluate the effects of the laser radiation (685 nm)
      associated with photosensitizers on viability of different species of Candida
      genus. Suspensions of Candida albicans, Candida dubliniensis, Candida krusei and
      Candida tropicalis, containing 10(6) viable cells per milliliter were obtained
      with the aid of a Neubauer's chamber. From each species, 10 samples of the cell
      suspension were irradiated with diode laser (685 nm) with 28 J/cm2 in the
      presence of methylene blue (0.1 mg/ml), 10 samples were only treated with
      methylene blue, 10 samples were irradiated with laser in the absence of the dye,
      10 samples were treated with the dye and irradiated with laser light and 10
      samples were exposed to neither the laser light nor to the methylene blue dye.
      From each sample, serial dilutions of 10(-2) and 10(-3) were obtained and
      aliquots of 0.1 ml of each dilution were plated in duplicate on Sabouraud
      dextrose agar. After incubation at 37 degrees C for 48 h, the number of colony
      forming units (CFU/ml) was obtained and data were submitted to ANOVA and Tukey's
      test (p<0.05). Laser radiation in the presence of methylene blue reduced the
      number of CFU/ml in 88.6% for C. albicans, 84.8% for C. dubliniensis, 91.6% for
      C. krusei and 82.3% for C. tropicalis. Despite this, only laser radiation or
      methylene blue did not reduce significantly the number of CFU/ml of Candida
      samples, except for C. tropicalis. It could be concluded that the photo
      activation of methylene blue by the red laser radiation at 685 nm presented
      fungicide effect on all Candida species studied.

PMID- 16413197
TI  - Anatomic characterization of human ultra-weak photon emission with a moveable
      photomultiplier and CCD imaging.
AB  - Ultra-weak photon emission of a living system has received scientific attention
      because of its potential for monitoring oxidative metabolism and oxidative damage
      to tissues. Heretofore, most studies have focused only on the emission from
      hands. The data regarding emission from other anatomic locations are limited. A
      previous multi-anatomic site recording of four subjects quantitatively
      demonstrated that the emission from several corresponding anatomic locations
      could differ by as much as a factor of 4. The data also suggested a "common"
      anatomic emission percentage distribution pattern. This information raised the
      question whether such a typical anatomic percentage emission exists. The
      objective of the present paper is to systematically replicate the emission from
      identical anatomic locations to document whether the anatomic percentage
      distribution pattern is generic. Part 1 includes the recording of ultra-weak
      photon emission from one sample subject over the torso, head and upper
      extremities with a highly sensitive charge-coupled device (CCD). Part 2 includes
      the analysis of that data to select a series of anatomic locations that were
      subsequently studied with a group of 20 subjects utilizing a highly sensitive,
      cooled and moveable (in three directions) photomultiplier system. Total sum
      emission of all recorded anatomic locations per subject fluctuates in this study
      almost 5-fold between subjects. However, the contribution of each anatomic
      location to the total emission from each subject was approximately the same
      percentage for each subject and similar to the sample CCD subject. The deviation
      of the anatomic percentage contribution for each subject was also established.
      The study presents evidence that there is a "common" anatomic percentage
      distribution pattern of ultra-weak photon emission for corresponding locations
      from each subject.

PMID- 16413198
TI  - Suramin prevents fulminant hepatic failure resulting in reduction of lethality
      through the suppression of NF-kappaB activity.
AB  - AIM: Suramin is a symmetrical polysulfonated naphthylamine derivative of urea.
      There have been few studies on the effect of suramin on cytokines. We examined
      the effects of suramin on production of inflammatory cytokines. METHODS: We made
      an acute liver injury model treated with d-galactosamine (GalN) and
      lipopolysaccharide (LPS). Plasma AST, ALT, tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-6 levels were measured. We compared with survival rate,
      histological found and NF-kappaB activity between with and without treatment of
      suramin. In macrophage like cell line, TNF-alpha and IL-6 production, TNF-alpha
      and IL-6 mRNA expression, and NF-kappaB activity was measured. RESULTS: The
      lethality of mice administered suramin with GalN/LPS was significantly decreased
      compared with that in mice without suramin. Changes of hepatic necrosis and
      apoptosis were slight in suramin-treated mice. Serum AST, ALT, TNF-alpha, IL-6
      levels and NF-kappaB activity in the liver were significantly lower in mice
      administered suramin. In an in vitro model, suramin preincubation inhibited TNF
      alpha and IL-6 production, TNF-alpha and IL-6 mRNA expression, and NF-kappaB
      activity. CONCLUSIONS: Suramin inhibits TNF-alpha and IL-6 production through the
      suppression of NF-kappaB activity from macrophages and shows therapeutic effects
      on acute liver damage.

PMID- 16413199
TI  - Analysis of serum and cerebrospinal fluid cytokine levels in subacute sclerosing
      panencephalitis in Papua New Guinea.
AB  - BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare progressive
      inflammatory disease characterized by the persistent infection of the brain by
      the measles virus. However, the immunological pathophysiology of SSPE is still
      unclear. METHODS: We measured the concentrations of interferon-gamma (IFN-gamma),
      tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10,
      and soluble TNF receptor 1 (sTNFR1) in the serum and cerebrospinal fluid (CSF) of
      23 patients with SSPE in Papua New Guinea (PNG), a country with a high incidence
      of SSPE, and Japanese controls by cytometric bead array or ELISA. RESULTS: The
      serum IL-6 and IL-10 levels of SSPE patients were significantly higher than those
      of controls (p=0.0075, and p=0.0019, respectively). The serum IL-6 and IL-10
      levels of SSPE patients with fever were significantly higher than those without
      fever (p=0.0107, and p=0.0006, respectively). The CSF IL-6 levels of SSPE
      patients were significantly higher than those of controls (p=0.0218). The CSF IL
      6 levels of SSPE patients with myoclonic jerks were significantly higher than
      those without myoclonic jerks (p=0.0189). There were no differences in serum IFN
      gamma, TNF-alpha, IL-2, IL-4, and sTNFR1, or CSF IFN-gamma, TNF-alpha, IL-2, IL
      4, IL-10, and sTNFR1 levels between the affected patients and controls.
      CONCLUSION: Our present study suggests that serum IL-6 and IL-10 levels are
      related to fever, and the CSF IL-6 level, myoclonic jerks, in SSPE patients in
      PNG.

PMID- 16413200
TI  - Using tandem mass spectrometry to predict chemical transformations of 2
      pyrimidinyloxy-N-arylbenzyl amine derivatives in solution.
AB  - Tandem mass spectrometry is used to predict the chemical transformations of 2
      pyrimidinyloxy-N-arylbenzyl amine derivatives. Compound 1, N-2-2-4,6-
      dimethoxypyrimidin-2-yloxy benzylamino phenyl benzamide was selected as a model
      to present our idea. The CID reactions of protonated 1 include an intramolecular
      S(N)2 reaction and a cyclodehydration reaction. Under in-source CID conditions,
      deprotonated 1 undergoes a Smiles rearrangement reaction and then dissociates to
      the ion at m/z 349. Theoretical computations were invoked to shed light on the
      reaction mechanisms of 1 by the semiempirical PM3 method. These studies of gas
      phase reactions show the reactivity of some potential reaction centers in this
      molecule, which inspired us to explore the solution phase analogous reactions of
      1. Further experiments show that 1 has two analogous reactions in acidic
      solution: the acid-catalyzed cyclodehydration reaction and the acid-catalyzed
      Smiles rearrangement reaction. Moreover, 1 undergoes the base-catalyzed Smiles
      rearrangement under basic conditions. The present study demonstrates that mass
      spectrometry can play an important role in predicting the chemical solution phase
      transformations of 2-pyrimidinyloxy-N-arylbenzyl amine derivatives.

PMID- 16413201
TI  - Factors influencing the electrospray intrasource separation and selective
      ionization of glycerophospholipids.
AB  - The external electric field induces a separation of cations from negative
      electrolyte ions in the infusate while differential ionization of molecular
      species that possess differential electrical propensities can be induced in
      either the positive- or negative-ion mode during the electrospray ionization
      process. These physical and electrical processes that occur in the electrospray
      ion source have been used to selectively ionize lipid classes possessing
      different electrical propensities that are now known as "intrasource separation
      and selective ionization". However, the chemical principles underlying charge
      dependent alterations in ionization efficiencies responsible for the selective
      ionization of lipid classes are not known with certainty. Herein, we examined the
      multiple factors that contribute to intrasource separation and selective
      ionization of lipid classes under optimal instrumental conditions. We
      demonstrated that many different lipid classes could be selectively ionized in
      the ion source and that intrasource resolution of distinct molecular constituents
      was independent of lipid concentration, flow rate, and residual ions under most
      experimental conditions. Moreover, the presence of alkaline conditions
      facilitates the selective ionization of many lipid classes through a mechanism
      independent of the design of the ESI ion source. Collectively, this study
      provides an empirical foundation for understanding the chemical mechanisms
      underlying intrasource separation and selective ionization of lipid classes that
      can potentially be used for global analysis of cellular lipidomes without the
      need for chromatographic separation.

PMID- 16413202
TI  - Factors affecting primary ionization in dopant-assisted atmospheric pressure
      photoionization (DA-APPI) for LC/MS.
AB  - The sensitivity of dopant-assisted atmospheric pressure photoionization (DA-APPI)
      for LC/MS is generally reduced at higher solvent flow rates. Theory suggests that
      quenching of excited-state precursors to the dopant ions, via collisions with
      vaporized solvent molecules, may be one mechanism responsible for this trend. To
      ascertain if the primary rate of ionization is affected by quenching, experiments
      were performed utilizing an ionization detector to determine the primary ion
      current generated by irradiating vaporized mixtures of toluene dopant and
      methanol solvent. The results indicate that no loss of primary ion current occurs
      as the solvent flow is increased, provided the dopant-to-solvent ratio is held
      constant. Additional primary ion current can always be generated by increasing
      the dopant flow rate and/or the lamp power. Thus, quenching of excited-state
      precursors to the dopant ions, leading to a reduction in the primary rate of
      ionization, is not the mechanism responsible for the observed loss of sensitivity
      at higher liquid solvent flow rates.

PMID- 16413203
TI  - Clustering of pentacene and functionalized pentacene ions in a matrix-assisted
      laser desorption/ionization orthogonal TOF mass spectrometer.
AB  - A high-performance orthogonal time-of flight (TOF) mass spectrometer, in
      combination with the matrix assisted laser desorption/ionization (MALDI) source
      operating at elevated pressure ( approximately 1 torr in N(2)), was used to
      perform MALDI-TOF analyses of pentacene and some of its derivatives with and
      without an added matrix. These molecules are among the most interesting
      semiconductor materials for organic thin film transistor applications (OTFT). The
      observation of ion-molecule reactions between "cold" analyte ions and neutral
      analyte molecules in the gas phase has provided some insight into the mechanism
      of pentacene cluster formation and its functionalized derivatives. Furthermore,
      some of the matrices employed to assist the desorption/ionization process of
      these compounds were observed to influence the outcome via ion-molecule reactions
      of analyte ions and matrix molecules in the gas phase. The stability and
      reactivity of the compounds and their clusters in the MALDI plume during gas
      phase expansion were evaluated; possible structures of the resulting clusters are
      discussed. The MALDI-TOF technique was also helpful in distinguishing between two
      isomeric forms of bis-[(triisopropylsilyl)-ethynyl]-pentacene.

PMID- 16413204
TI  - Significant parameters in the optimization of MALDI-TOF-MS for synthetic
      polymers.
AB  - One of the most significant issues in any analytical practice is optimization.
      Optimization and calibration are key factors in quantitation. In matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS),
      instrument optimization is a limitation restricting quantitation. An
      understanding of the parameters that are most influential and the effects of
      these parameters on the mass spectrum is required for optimization. This
      understanding is especially important when characterizing synthetic polymers by
      MALDI-TOF-MS, due to the breadth of the polymer molecular mass distribution
      (MMD). Two considerations are important in quantitation, additivity of signal and
      signal-to-noise (S/N). In this study, the effects of several instrument
      parameters were studied using an orthogonal experimental design to understand
      effects on the signal-to-noise (S/N) of a polystyrene distribution. The
      instrument parameters examined included detector voltage, laser energy, delay
      time, extraction voltage, and lens voltage. Other parameters considered were
      polymer concentration and matrix. The results showed detector voltage and delay
      time were the most influential of the instrument parameters for polystyrene using
      all trans-retinoic acid (RA) as the matrix. These parameters, as well as laser
      energy, were most influential for the polystyrene with dithranol as the matrix.

PMID- 16413205
TI  - Detection of aqueous phase chemical warfare agent degradation products by
      negative mode ion mobility time-of-flight mass spectrometry [IM(tof)MS].
AB  - The use of negative ion monitoring mode with an atmospheric pressure ion mobility
      orthogonal reflector time-of-flight mass spectrometer [IM(tof)MS] to detect
      chemical warfare agent (CWA) degradation products from aqueous phase samples has
      been determined. Aqueous phase sampling used a traditional electrospray
      ionization (ESI) source for sample introduction and ionization. Certified
      reference materials (CRM) of CWA degradation products for the detection of
      Schedule 1, 2, or 3 toxic chemicals or their precursors as defined by the
      chemical warfare convention (CWC) treaty verification were used in this study. A
      mixture of six G-series nerve related CWA degradation products (EMPA, IMPA, EHEP,
      IHEP, CHMPA, and PMPA) and their related collision induced dissociation (CID)
      fragment ions (MPA and EPA) were found in each case to be clearly resolved and
      detected using the IM(tof)MS instrument in negative ion monitoring mode.
      Corresponding ions, masses, drift times, K(o) values, and signal intensities for
      each of the CWA degradation products are reported.

PMID- 16413206
TI  - Combining low and high mass ion accumulation for enhancing shotgun proteome
      analysis by accurate mass measurement.
AB  - A simple procedure is described that increases sensitivity and dynamic range for
      the analysis of a proteome batch digest by FT-ICR mass spectrometry. Ions at the
      low and high mass ranges are preferentially collected using two different sets of
      tuning conditions. By combing data collected using tuning conditions that favor
      low mass (m/z < 2000) and high mass (m/z > 2000) ions, 277 proteins are
      identified for a whole cell lysate of Methanococcus maripaludis in a single HPLC
      MALDI FT-ICR mass spectrometry experiment, a 70% improvement compared with
      previous analyses using a wide mass range acquisition. This procedure improves
      the detection of low abundance ions and thereby increases the range of proteins
      that are observed. Because the observed mass range is effectively narrower for
      each spectrum, mass calibration is more accurate than for the standard method
      that provides a wide range of masses. The trap plate potential on the analyzer
      cell may be set to a higher value than used for wide mass range measurements,
      increasing the ion capacity of the analyzer cell and extending the dynamic range,
      while still maintaining mass accuracy.

PMID- 16413207
TI  - ESI-FTICR mass spectrometric study of alcohol complexation properties of mono-
      and diphosphonate-bridged cavitands.
AB  - Alcohol complexation properties of eight mono- and diphenyl phosphonate-bridged
      cavitands were studied by electrospray ionization Fourier transform ion cyclotron
      resonance mass spectrometry (ESI-FTICR) and theoretical calculations. The
      cavitands varied in number and position of phenyl phosphonate bridges and their
      orientation with respect to the cavity, length of the lower rim alkyl chains, and
      substituents at apical positions of the resorcarene skeleton. The specificities
      of the different cavitands toward primary, secondary, and tertiary alcohols
      varying long of the alkyl chain were investigated, together with the stabilities
      of the formed complexes. The number, position, and orientation of the P = O
      moieties affected the complex formation of the cavitands and stability of the
      complexes dramatically. Methyl groups at apical positions of the resorcarene
      skeleton also affected the complexation properties. Although length and branching
      of the alkyl chain of the alcohol influenced the complex formation, the effect on
      stability of the complexes was negligible.

PMID- 16413208
TI  - Dietary administration of bovine lactoferrin influences the immune ability of the
      giant freshwater prawn Macrobrachium rosenbergii (de Man) and its resistance
      against Aeromonas hydrophila infection and nitrite stress.
AB  - Haemocyte count, phenoloxidase activity, agglutinin levels, total protein
      content, bacterial clearance efficiency, resistance to the pathogen Aeromonas
      hydrophila and nitrite stress were measured in the giant freshwater inter-moult
      sub-adult prawn Macrobrachium rosenbergii (15-20 g) which had been fed diets
      containing bovine lactoferrin (Lf) at 50, 100, 200mg kg(-1) feed for 7 or 14
      days. M. rosenbergii fed a diet containing 100mg Lf kg(-1) diet for 7 days showed
      significant (P<0.05) increase in total protein levels, agglutination titres
      against bacteria A. hydrophila and rabbit RBC, phenoloxidase activity, bacterial
      clearance (as observed through reduced number of circulating bacteria) as well as
      survival against A. hydrophila challenge. Increased bacterial clearance was also
      noticed in prawns fed Lf at 50 or 200mg kg(-1) for 14 days compared to control.
      Feeding of Lf at 50mg kg(-1) diet for 7 or 14 days was able to enhance only PO
      activity and reduce percent mortality against A. hydrophila challenge compared to
      its control. Total haemocyte count was higher in the lowest dose of Lf feeding,
      i.e. 50mg kg(-1) for 7 days. However, there was no significant alteration in the
      differential haemocyte population with respect to graded levels of Lf feeding for
      7 or 14 days. A notable reduction in mortality percent after 120 h of nitrite
      stress was observed in prawn fed Lf at 100mg kg(-1) diet for 14 days. On the
      contrary, feeding of the highest dose of Lf, i.e. 200mg kg(-1) diet for 14 days
      failed to stimulate most of the innate immune parameters or reduce the percent
      mortality against A. hydrophila challenge or nitrite stress. It is therefore
      concluded that administration of Lf in the diet at 100mg kg(-1) for 7 days could
      enhance the immune ability of M. rosenbergii and increase its resistance to A.
      hydrophila infection or nitrite stress.

PMID- 16413209
TI  - Frequency flows and the time-frequency dynamics of multivariate phase
      synchronization in brain signals.
AB  - The quantification of phase synchrony between brain signals is of crucial
      importance for the study of large-scale interactions in the brain. Current
      methods are based on the estimation of the stability of the phase difference
      between pairs of signals over a time window, within successive frequency bands.
      This paper introduces a new approach to study the dynamics of brain synchronies,
      Frequency Flows Analysis (FFA). It allows direct tracking and characterization of
      the nonstationary time-frequency dynamics of phase synchrony among groups of
      signals. It is based on the use of the one-to-one relationship between frequency
      locking and phase synchrony, which applies when the concept of phase synchrony is
      not taken in an extended 'statistical' sense of a bias in the distribution of
      phase differences, but in the sense of a continuous phase difference conservation
      during a short period of time. In such a case, phase synchrony implies identical
      instantaneous frequencies among synchronized signals, with possible time varying
      frequencies of synchronization. In this framework, synchronous groups of signals
      or neural assemblies can be identified as belonging to common frequency flows,
      and the problem of studying synchronization becomes the problem of tracking
      frequency flows. We use the ridges of the analytic wavelet transforms of the
      signals of interest in order to estimate maps of instantaneous frequencies and
      reveal sustained periods of common instantaneous frequency among groups of
      signal. FFA is shown to track complex dynamics of synchrony in coupled oscillator
      models, reveal the time-frequency and spatial dynamics of synchrony convergence
      and divergence in epileptic seizures, and in MEG data the large-scale ongoing
      dynamics of synchrony correlated with conscious perception during binocular
      rivalry.

PMID- 16413210
TI  - Associations among preoperative MRI features and functional status following
      arthroscopic partial meniscectomy.
AB  - BACKGROUND: Arthroscopic partial meniscectomy (APM) is the most frequently
      performed orthopedic procedure. Functional outcomes of APM are variable,
      particularly among patients with underlying knee osteoarthritis. While most
      patients undergoing APM have knee magnetic resonance imaging (MRI) performed
      preoperatively, the prognostic value of knee MRI in predicting the functional
      outcomes of APM has not been evaluated. METHODS: We studied patients who had APM
      performed by one of five participating surgeons at one institution in 2002. The
      preoperative MRI scans of these patients were assessed using a standardized
      rating system by an independent observer who was not involved in the care of the
      patients and who was blinded to patient outcomes. Patients completed a
      questionnaire in the summer of 2003, 6-18 months postoperatively. The
      questionnaire included the Knee Injury and Osteoarthritis Outcome Score (KOOS)
      and items on satisfaction with the results of surgery. We used bivariate and
      multivariate techniques to evaluate the associations between MRI findings, other
      preoperative findings, and the functional status and pain scales of the KOOS.
      RESULTS: Eighty-three patients were included in the analyses. The outcome of
      surgery was variable with average KOOS functional score of 77 and range of 15
      100. One-quarter of patients were somewhat or very dissatisfied with the results
      of surgery and 17% were using a cane at the time of follow-up. In bivariate
      analyses, preoperative predictors of KOOS function score at follow-up included
      preoperative functional status and several MRI findings including the extent of
      cartilage damage, bone marrow edema in the medial compartment, and length of the
      tear. Multivariate analyses showed that after adjusting for preoperative
      functional status, the extent of cartilage signal abnormality in the medial
      compartment on MRI remained an independent predictor of functional status, 6-18
      months following surgery. Specifically, preoperative functional status explained
      21% of the variability in follow-up KOOS functional status score and the extent
      of medial tibial cartilage damage on MRI explained an additional 16%. Analyses of
      knee pain 1 year following APM yielded similar findings, with preoperative
      functional status accounting for 17% of the variability in pain scores and medial
      tibial cartilage damage accounting for an additional 13%. CONCLUSIONS:
      Preoperative MRI findings of cartilage damage have independent prognostic value
      in predicting the functional outcome of APM. This study was limited by a cross
      sectional design with retrospective recall of preoperative functional status.
      Thus, the findings need to be confirmed in prospective investigations.

PMID- 16413211
TI  - Pomegranate juice reduces oxidized low-density lipoprotein downregulation of
      endothelial nitric oxide synthase in human coronary endothelial cells.
AB  - We examined the hypothesis that pomegranate juice (PJ) can revert the potent
      downregulation of the expression of endothelial nitric-oxide synthase (NOSIII)
      induced by oxidized low-density liporotein (oxLDL) in human coronary endothelial
      cells. Western blot and Northern blot analyses showed a significant decrease of
      NOSIII expression after a 24-h treatment with oxLDL. Accordingly, we observed a
      significant dose-dependent reduction in nitric oxide bioactivity represented by
      both basal and bradykinin-stimulated cellular cGMP accumulation. These phenomena
      were corrected significantly by the concomitant treatment with PJ. Our data
      suggest that PJ can exert beneficial effects on the evolution of clinical
      vascular complications, coronary heart disease, and atherogenesis in humans by
      enhancing the NOSIII bioactivity.

PMID- 16413212
TI  - Nitric oxide production from rat adipocytes is modulated by beta3-adrenergic
      receptor agonists and is involved in a cyclic AMP-dependent lipolysis in
      adipocytes.
AB  - It is established that the modulation of beta(3)-adrenoceptor function could be
      associated with impairment of lipolysis in white fat and be responsible for
      disturbed lipid metabolism. Though two isoforms of nitric oxide synthase (NOS)
      were reported in adipocytes, the role of nitric oxide (NO) in adipose tissue is
      still ambiguous. The present work was directed to study the interplay between NO
      production and beta-adrenoceptor/cyclic AMP (cAMP) pathway on lipid mobilization
      (glycerol and nonesterified fatty acids, NEFA) in cultures of rat adipocytes
      isolated from epididymal white adipose tissue. beta-Nonselective (isoprenaline)
      and beta(3)-selective (BRL-37344) agonists and the postadrenoceptor agents such
      as dibutyryl-cAMP, forskolin, and 3-isobutyl-1-methylxanthine significantly
      increased nitrite, glycerol, and NEFA levels with BRL-37344 being the most
      potent. Conversely, addition of beta-nonselective (propranolol) or beta(3)
      selective (bupranolol) antagonist or the adenylyl cyclase inhibitor (SQ 22,536)
      significantly reduced beta-agonist-induced NO production and lipolysis. For beta
      adrenoceptor agonists, antagonists, and their pairs, there was a positive
      correlation between medium nitrite and glycerol or NEFA with r(2) being 0.90 and
      0.84, respectively. The possible relationship between NO and lipolysis was
      revealed after adipocyte treatment with nonspecific (N(omega)-nitro-l-arginine
      methyl ester, l-NAME) and specific (aminoguanidine) NOS inhibitors. Both l-NAME
      and aminoguanidine significantly inhibited the lipolytic effect of BRL-37344.
      Moreover, NO-donor (S-nitroso-N-acetylpenicillamine) at higher concentration
      increased basal glycerol and NEFA levels. 8-bromo-cyclic GMP had no effect on
      adipocyte lipolysis. These data suggest that beta-adrenergic lipolysis,
      specifically beta(3)-adrenoceptor effect, which is realized via the adenylyl
      cyclase/cAMP/protein kinase A signaling cascade, involves NO production
      downstream of beta(3)-adrenoceptor/cAMP pathway.

PMID- 16413213
TI  - Reduction of mucin-1 gene expression associated with increased Escherichia coli
      adherence in the canine uterus in the early stage of dioestrus.
AB  - The relation between adherence of Escherichia coli and expression of mucin-1
      (Muc1: an integral membrane mucin) mRNA in the endometrium was studied in beagle
      bitches at different stages of the oestrous cycle and in those with cystic
      endometrial hyperplasia/pyometra complex (pyometra). The number of E. coli
      adhering to the endometrium was low at pro-oestrus and oestrus and increased at
      the early stage (day 10) of dioestrus, corresponding to the implantation period;
      it declined thereafter. Adhesion of the organisms to endometrial epithelial cells
      collected at day 10 of dioestrus was inhibited by the addition of D-mannose. When
      endometrial epithelial cells collected at pro-oestrus were treated with
      hyaluronidase, an enzyme that digests mucins, the numbers of E. coli adhering to
      the cells tended to increase. With polymerase chain reaction analysis it was
      possible to detect Muc1 gene transcripts in the endometrium at all stages of the
      oestrous cycle, although the level of Muc1 mRNA decreased by day 10 of dioestrus.
      The levels of Muc1 mRNA in bitches with a clinical stage of pyometra were low and
      comparable to those at day 10 of dioestrus. The number of E. coli adhering to the
      endometrium and Muc1 mRNA levels in the endometrium were inversely correlated (r=
      0.77, P<0.01). Immunohistochemical analysis showed little staining for Muc1 in
      the endometrial epithelia at day 10 of dioestrus and in bitches with pyometra.
      These results suggest that reduction of Muc1 expression is associated with
      increased E. coli adherence in the canine uterus at the early stage of dioestrus,
      possibly facilitating the development of pyometra.

PMID- 16413214
TI  - Bilateral renal agenesis, cerebral angiodysplasia and esophageal atresia.
AB  - The combination of bilateral renal agenesis, vascular abnormalities in the brain
      and esophageal atresia is exceptional. MR and ultrasound data of the brain
      findings are presented for the first time in such a case.

PMID- 16413215
TI  - Intensity and mosaic spread analysis from PISEMA tensors in solid-state NMR.
AB  - The solid-state NMR experiment PISEMA, is a technique for determining structures
      of proteins, especially membrane proteins, from oriented samples. One method for
      determining the structure is to find orientations of local molecular frames
      (peptide planes) with respect to the unit magnetic field direction, B0. This is
      done using equations that compute the coordinates of this vector in the frames.
      This requires an analysis of the PISEMA function and its degeneracies. As a
      measure of the sensitivity of peptide plane orientations to the data, we use
      these equations to derive a formula for the intensity function in the powder
      pattern. With this function and other measures, we investigate the effect of
      small changes in peptide plane orientations depending on the location of the
      resonances in the powder pattern spectrum. This gives us an indication of the
      change in lineshape due to mosaic spread and a way to interpret these in terms of
      an orientational error bar.

PMID- 16413216
TI  - Breath tests and airway gas exchange.
AB  - Measuring soluble gas in the exhaled breath is a non-invasive technique used to
      estimate levels of respiratory, solvent, and metabolic gases. The interpretation
      of these measurements is based on the assumption that the measured gases exchange
      in the alveoli. While the respiratory gases have a low blood-solubility and
      exchange in the alveoli, high blood-soluble gases exchange in the airways. The
      effect of airway gas exchange on the interpretation of these exhaled breath
      measurements can be significant. We describe airway gas exchange in relation to
      exhaled measurements of soluble gases that exchange in the alveoli. The
      mechanisms of airway gas exchange are reviewed and criteria for determining if a
      gas exchanges in the airways are provided. The effects of diffusion, perfusion,
      temperature and breathing maneuver on airway gas exchange and on measurement of
      exhaled soluble gas are discussed. A method for estimating the impact of airway
      gas exchange on exhaled breath measurements is presented. We recommend that
      investigators should carefully control the inspired air conditions and type of
      exhalation maneuver used in a breath test. Additionally, care should be taken
      when interpreting breath tests from subjects with pulmonary disease.

PMID- 16413218
TI  - Characterization of a partial alpha-amylase clone from red porgy (Pagrus pagrus):
      expression during larval development.
AB  - A partial alpha-amylase cDNA was isolated from red porgy (Pagrus pagrus,
      Teleostei: Sparidae) and its tissue specific expression during larval development
      was examined. The cDNA was 949 bp long and showed 90% identity with other fish
      amylases. A 545 bp fragment was used to study amylase expression using in situ
      hybridization and RT-PCR techniques. Both methods showed a similar pattern: high
      and relatively constant expression for the first 30 days after hatching (dah),
      subsequently decreasing until the end of the experiment at 60 dah. The goal of
      this work was to extend the existing knowledge of the functionality of larval
      fish digestive systems and to provide new information about alpha-amylase gene
      expression.

PMID- 16413217
TI  - Two types of phosphofructokinase-1 differentially regulate the glycolytic pathway
      in insulin-stimulated chicken skeletal muscle.
AB  - To elucidate the precise regulation of glucose homeostasis in chicken skeletal
      muscle, expression of muscle- and liver-type phosphofructokinase-1 (EC:2.7.1.11,
      PFK-M, PFK-L) was characterized in the insulin-stimulated state by Real-Time PCR.
      Firstly, chicken PFK-M and PFK-L full-length cDNA sequences were identified. The
      deduced amino acid sequences were 81.6% and 86.5% identical with human PFK-M and
      PFK-L, respectively. In pectoralis superficialis (PS) muscle and extensor
      digitorum longus (EDL), PFK-M mRNA levels were unchanged following insulin
      stimulation. Surprisingly, although mammalian PFK-L has been reported to be
      expressed in liver, kidney and brain, chicken PFK-L was not detected in liver and
      kidney, however, strong expression was detected in skeletal muscle and brain by
      Northern blot analysis. However, using PCR, PFK-L mRNA was detected in liver.
      Taken together, chicken PFK-L mRNA expression was at a very low level, below the
      detection limit of Northern blot analysis. Chicken PFK-L mRNA levels were
      increased 200% in PS muscle but decreased by 40% in EDL following insulin
      stimulation. These results suggest that two types of PFK regulate the glycolytic
      pathway in the insulin-stimulated state and, therefore, that glucose metabolism
      in chicken skeletal muscle may be regulated in a very different manner compared
      to mammals.

PMID- 16413219
TI  - Pituitary tuberculosis presenting as pituitary apoplexy.

PMID- 16413220
TI  - Osteoprotegerin (OPG) binds with tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL): suppression of TRAIL-induced apoptosis in ameloblastomas.
AB  - Osteoprotegerin (OPG) is a useful receptor in inhibiting Receptor Activator of
      NFkappaB Ligand (RANKL) in inducing osteoclastogenesis. Tumor Necrosis Factor
      (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) is a potent apoptosis-inducing
      ligand in ameloblastomas. Since OPG has been reported to bind to TRAIL as well,
      the effect of OPG in TRAIL's function in inducing apoptosis should also be
      investigated. To investigate on the expression of OPG in ameloblastomas,
      immuhistochemistry, immunofluorescence and Western blot were performed. From the
      immunohistochemistry results, we found that OPG was expressed in ameloblastoma
      tissues. Expression of OPG was clearly seen in AM-1 cells by immunofluorescence
      as well. Additionally, Western blot analysis confirmed OPG expression in
      ameloblastoma tissues and AM-1 cells. To investigate on the potential of
      TNFalpha, TRAIL and RANKL in inducing apoptosis, we performed an apoptosis assay.
      From the apoptosis assay, we found that TRAIL had the highest potential in
      inducing apoptosis compared to TNFalpha and RANKL. To investigate the binding of
      OPG with RANKL and TRAIL, we performed a binding assay. We noticed that OPG
      preferably bind with RANKL than TRAIL. However, at low levels of RANKL, marked
      binding of OPG with TRAIL was seen. As we suspected that the binding of OPG and
      TRAIL might cause the effect of TRAIL in inducing apoptosis in ameloblastomas, we
      combined the treatment of OPG and TRAIL in AM-1 cells. From the apoptosis assay,
      we found that under treatment of OPG, TRAIL's function in inducing apoptosis was
      suppressed. These data suggest that by binding with TRAIL, OPG suppressed TRAIL's
      function in inducing apoptosis in ameloblastomas.

PMID- 16413221
TI  - Salmonella transcriptomics: relating regulons, stimulons and regulatory networks
      to the process of infection.
AB  - The advent of Salmonella transcriptomics has heralded a new era for gene
      expression analysis of this formidable intracellular pathogen. Increasing numbers
      of Salmonella transcriptomic datasets will contribute to the comprehensive
      definition of regulons, stimulons and regulatory networks. This task has
      highlighted the need for sophisticated computational techniques to describe
      regulatory interactions.

PMID- 16413223
TI  - The role of oxidative stress in glaucoma.
AB  - DNA damage is related to a variety of degenerative diseases such as cancer,
      atherosclerosis and neurodegenerative diseases, depending on the tissue affected.
      Increasing evidence indicates that reactive oxygen species (ROS) play a key role
      in the pathogenesis of primary open angle glaucoma (POAG), the main cause of
      irreversible blindness worldwide. Oxidative DNA damage is significantly increased
      in the ocular epithelium regulating aqueous humor outflow, i.e., the trabecular
      meshwork (TM), of glaucomatous patients compared to controls. The pathogenic role
      of ROS in glaucoma is supported by various experimental findings, including (a)
      resistance to aqueous humor outflow is increased by hydrogen peroxide by inducing
      TM degeneration; (b) TM possesses remarkable antioxidant activities, mainly
      related to superoxide dismutase-catalase and glutathione pathways that are
      altered in glaucoma patients; and (c) intraocular-pressure increase and severity
      of visual-field defects in glaucoma patients parallel the amount of oxidative DNA
      damage affecting TM. Vascular alterations, which are often associated with
      glaucoma, could contribute to the generation of oxidative damage. Oxidative
      stress, occurring not only in TM but also in retinal cells, appears to be
      involved in the neuronal cell death affecting the optic nerve in POAG. The
      highlighting of the pathogenic role of ROS in POAG has implications for the
      prevention of this disease as indicated by the growing number of studies using
      genetic analyses to identify susceptible individuals and of clinical trials
      testing the efficacy of antioxidant drugs for POAG management.

PMID- 16413222
TI  - Genotoxicity and toxicity assessment in urban hydrographic basins.
AB  - The genotoxicity and cytotoxicity of water in small urban basins was evaluated by
      the Salmonella/microsome assay and micronucleus test in V79 cells. The results
      showed that the cytotoxic effect was the most significant response in areas with
      medium to heavy urban occupation for both assays evaluated. Water samples from
      these areas include different concentrations of chloroform, bromodichloromethane,
      toluene, ethylbenzene, m,p-xylene and 1,4-dichlorobenzene. As to genotoxic
      damage, the presence of mainly direct-acting frameshift mutagens was detected in
      areas with less urban concentration and showed genotoxic activity in V79 cells in
      more heavily urbanized areas. Water organic extracts, evaluated using a
      microsuspension procedure, showed frameshift mutagenic activity in the presence
      of hepatic metabolization that increased as the population density grow. Chronic
      toxicity studies of sediment samples with the microcrustacean Daphnia magna
      showed that, while survival was not highly affected, reproductive inhibition was
      found in 92% of the observations. A retrospective diagnosis of water quality
      using traditional physicochemical parameters that defined the differential
      contribution of urban wastes at the three sites was associated with the
      biological assays. It became clear that the biological assays were of significant
      benefit in the diagnosis of risks of contamination of hydrographic basins by
      pollutants from urban non-point sources.

PMID- 16413224
TI  - GC-rich sequences in the 5-lipoxygenase gene promoter are required for expression
      in Mono Mac 6 cells, characterization of a novel Sp1 binding site.
AB  - 5-lipoxygenase (5LO) catalyzes formation of leukotrienes, mediators with roles in
      several inflammatory disorders, including atherosclerosis. The human 5LO gene
      promoter contain multiple GC-boxes. The relevance of these for expression of 5LO
      in the human monocytic cell line Mono Mac 6 (MM6) was studied. A downregulating
      effect of the GC-box binding compound mithramycin indicated that GC-rich
      sequences in the 5LO gene promoter are important for expression of native 5LO. In
      DNase I footprinting, mithramycin and Sp1 protected known GC-boxes, but also a
      novel Sp1 binding site was found, comprising 20 bp upstream of the major
      transcription initiation site, beside an Initiator-like sequence. Mutation of
      this site reduced Sp1 binding and expression of reporter genes in MM6 cells,
      compatible with a function as basal promoter element for the TATA-less 5LO gene.
      When differentiation was induced by TGFbeta and vitamin D(3), 5LO expression
      became prominent, but expression levels of Sp1/3 and Egr-1 were the same as for
      control cells. Also, 5LO reporter gene activity in transiently transfected MM6
      cells was insensitive to differentiation. Thus, the GC-rich part of the 5LO gene
      promoter, including a novel Sp1 site, appear important for basal (rather than
      upregulated) transcription of 5LO in MM6 cells.

PMID- 16413226
TI  - T lymphocytes on the move: chemokines, PI 3-kinase and beyond.
AB  - The ordered, directional migration of T lymphocytes is a key process in
      development, immune surveillance and the immune response. Chemokines have an
      important role in the guidance of T lymphocytes and activate several members of
      the phosphoinositide 3-kinase (PI 3-kinase) family, which contribute to various
      aspects of the migratory machinery in many cell systems. However, the role of PI
      3-kinase in T-cell movement is unclear, and its importance has been largely
      dismissed. Over the past two years, there has been exciting progress in our
      appreciation not only of the finer details of PI 3-kinase involvement in T-cell
      migration, but also of other signalling events that probably influence T-cell
      migration in response to recognized chemoattractants. These aspects of T-cell
      migration are the subject of this review.

PMID- 16413225
TI  - Direct evidence in vivo of impaired macrophage-specific reverse cholesterol
      transport in ATP-binding cassette transporter A1-deficient mice.
AB  - The ATP-binding cassette transporter A1 (ABCA1) is a key regulator of high
      density lipoprotein (HDL) metabolism. There is strong evidence that ABCA1 is a
      key regulator of reverse cholesterol transport (RCT). However, this could not be
      proved in vivo since hepatobiliary cholesterol transport was unchanged in ABCA1
      deficient mice (ABCA1-/-). We used ABCA1-/- mice to test the hypothesis that
      ABCA1 is a critical determinant of macrophage-specific RCT. Although this cell
      specific RCT only accounts for a tiny part of total RCT, it is widely accepted
      that it may have a major impact on atherosclerosis susceptibility.
      [(3)H]cholesterol-labeled endogenous macrophages were injected intraperitoneally
      into wild-type ABCA1+/+, ABCA1+/- and ABCA1-/- mice maintained on a chow diet. A
      direct relationship was observed between ABCA1 gene dose and plasma
      [(3)H]cholesterol at 24 and 48 h after the injection of tracer into the mice.
      Forty-eight hours after this injection, ABCA1-/- mice had significantly reduced
      [(3)H]cholesterol in liver (2.8-fold), small intestine enterocytes (1.7-fold) and
      feces (2-fold). To our knowledge, this is the first direct in vivo quantitative
      evidence that ABCA1 is a critical determinant of macrophage-specific RCT.

PMID- 16413227
TI  - STAT4/6-dependent differential regulation of chemokine receptors.
AB  - The major cell fate decision of the CD4+ helper T cells is the development of Th1
      and Th2 phenotype, the balance of which determines the outcome of a wide variety
      of autoimmune responses. Signal transducers and activators of transcription
      (STATs), in particular STAT4 and STAT6, are essential for the development of Th1
      and Th2 cells, respectively. We used Balb/c mice lacking STAT4 or STAT6 to
      explore the ability of helper T cells to express chemokine receptors. We
      demonstrated that both STAT4-/- and STAT6-/- CD4+ lymphocytes showed impaired
      expansion as well as differentiation into IFN-gamma-secreting Th1 cells and IL2-,
      IL4-, IL10-secreting Th2 cells. Interestingly, the expression of chemokine
      receptors, which is STAT4/6-dependent, was differentially regulated via two
      distinct mechanisms, positively (CCR3, CCR4) and negatively (CCR5, CCR7). These
      results provide the basis for STAT-dependent differential regulation of chemokine
      receptors in Th subsets.

PMID- 16413228
TI  - Transduction characteristics of adeno-associated virus vectors expressing cap
      serotypes 7, 8, 9, and Rh10 in the mouse brain.
AB  - Recombinant adeno-associated viral (AAV) vectors can transduce cells of the CNS,
      resulting in long-term expression. AAV vector transduction varies depending on
      the serotype used and the region of the brain injected. AAV serotypes 7, 8, 9,
      and Rh10 have recently become available, but the transduction capabilities of
      these serotypes within the CNS have not been determined. We show that AAV 7, 8,
      9, and Rh10 vectors expressing cDNA for a lysosomal enzyme transduce neurons, but
      not astrocytes or oligodendrocytes, in the cortex, striatum, hippocampus, and
      thalamus. Although all of the vectors contained the same genome, there were
      markedly different transduction patterns that could be due only to the
      differences in capsid proteins. The AAV 9 vector was found to undergo vector
      genome transport to distal neuronal cell bodies via known axonal pathways. This
      facilitated the distribution of enzyme, resulting in correction of lysosomal
      storage lesions in regions of a diseased brain that would not be corrected if the
      genome were not transported.

PMID- 16413229
TI  - Factors motivating dyspepsia patients to enter clinical research.
AB  - One of the most influential factors in science and medicine has been the
      development of placebo-controlled clinical trials. However, recruitment of
      patients for clinical trials is sometimes a major problem in clinical research.
      Successful patient recruitment may be enhanced with a clear understanding of the
      motivating factors that determine a patient's decision to enter a study. We have
      developed the Patients' Expectations, Attitudes and Knowledge (PEAK) Program
      consisting of questionnaires designed to study the factors motivating patients to
      enter a clinical trial, as well as capturing the experiences of research
      participants. A total of 247 female patients with dyspepsia (mean age: 43.9;
      range: 18.0-78.0 years) who entered either of two prospective double-blind,
      randomized, placebo-controlled multicenter trials in the USA completed PEAK Entry
      questionnaires during the first study visit. Based on their responses, the top
      three factors motivating patients to join the clinical trial were: interest in
      receiving investigational treatment with average score (AS) of 4.33 +/- 0.08 (M
      +/- SEM) on a 5-point scale, possibility of getting skilled professional care (AS
      = 4.07 +/- 0.09), and altruism expressed as an intention to help develop a new
      drug for the sake of other people (AS = 3.89 +/- 0.09). Age, ethnicity, and
      educational status significantly affected motivational factors of patients. These
      results indicate that recruitment can be enhanced by targeting these motivations
      in physician/patient communications, informed consent process and advertising for
      study participants.

PMID- 16413230
TI  - XPA protein as a limiting factor for nucleotide excision repair and UV
      sensitivity in human cells.
AB  - Nucleotide excision repair (NER) acts on a variety of DNA lesions, including
      damage induced by many chemotherapeutic drugs. Cancer therapy with such drugs
      might be improved by reducing the NER capacity of tumors. It is not known,
      however to what extent any individual NER protein is rate-limiting for any step
      of the repair reaction. We studied sensitivity to UV radiation and repair of DNA
      damage with regard to XPA, one of the core factors in the NER incision complex.
      About 150,000-200,000 molecules of XPA protein are present in NER proficient
      human cell lines, and no XPA protein in the XP-A cell line XP12RO. Transfected
      XP12RO cell lines expressing 50,000 or more XPA molecules/cell showed UV
      resistance similar to normal cells. Suppression of XPA protein to approximately
      10,000 molecules/cell in a Tet-regulatable system modestly but significantly
      increased sensitivity to UV irradiation. No removal of cyclobutane pyrimidine
      dimers was detected in the SV40 immortalized cell lines tested. Repair proficient
      WI38-VA fibroblasts and transfected XP-A cells expressing 150,000 molecules of
      XPA/cell removed (6-4) photoproducts from the genome with a half-life of 1h.
      Cells in which XPA protein was reduced to about 10,000 molecules/cell removed (6
      4) photoproducts more slowly, with a half-life of 3h. A reduced rate of repair of
      (6-4) photoproducts thus results in increased cellular sensitivity towards UV
      irradiation. These data indicate that XPA levels must be reduced to <10% of that
      present in a normal cell to render XPA a limiting factor for NER and consequent
      cellular sensitivity. To inhibit NER, it may be more effective to interfere with
      XPA protein function, rather than reducing XPA protein levels.

PMID- 16413231
TI  - Oxygenation in the motor cortex during exhaustive pinching exercise.
AB  - The purpose of this study was to examine the effect of fatigue resulting from
      exhaustive pinching exercise on frontal and motor cortex activity. Eight healthy
      subjects (four male and four female) participated in the present study. All
      subjects performed at 70% of maximal voluntary contraction (MVC) pinching
      exercise until reaching a state of volitional fatigue. Frontal cortex and motor
      cortex oxygenation was measured by near-infrared spectroscopy throughout the
      exhaustive exercise. Frontal cortex and motor cortex oxygenation increased
      significantly at the 90 and 120 s after the start of exercise compared with the
      pre-exercise values and these decreased with the time passage. Frontal cortex
      oxygenation at exhaustion was significantly lower than the 90 and 120 s after the
      start of exercise, while motor oxygenation at exhaustion was the same value with
      the pre-exercise value. These findings suggest that the exhaustive exercise
      induces the decrease of cerebral function and that the fatigue resulting from
      dynamic exercise decreases the motor cortex activity.

PMID- 16413232
TI  - Expression and physicochemical characterization of an extracellular segment of
      the receptor protein tyrosine phosphatase IA-2.
AB  - The receptor protein tyrosine phosphatase superfamily (RPTP) includes proteins
      with a single transmembrane, one or more intracellular phosphatase, and a variety
      of extracellular domains. The 106-kDa insulinoma-associated protein (IA-2,
      ICA512) receptor is unique among RPTP members because: (a) it has a single,
      phosphatase-like intracellular domain identified as one of the most prominent
      self antigens in autoimmune diabetes; (b) its extracellular region bears no
      sequence similarity to known domains; (c) it is present in the membrane of
      secretory granules in neurons and pancreatic beta-cells where it suffers a
      complex processing; and (d) it has very poorly understood biological properties.
      In this work, we describe the expression, purification, and physicochemical
      characterization of residues 449-576 of IA-2 (IA-2ec(449-576)). Judging from CD,
      fluorescence, hydrodynamic, and thermal unfolding analyses, this fragment forms
      an autonomously folding unit with tight packing and well-defined secondary and
      tertiary structure. CD analysis suggests that about 25% of IA-2ec(449-576)
      residues are alpha-helical, whereas about the same amount are in beta-sheet
      structure. The availability of soluble and folded IA-2ec(449-576) is a step
      forward toward the characterization of a part of IA-2 at atomic detail, which may
      provide new insight in the biology of diabetes, the neurotransmission process,
      and the dynamic of secretory granules.

PMID- 16413233
TI  - Long-term clinical course of extra-oesophageal manifestations in patients with
      gastro-oesophageal reflux disease. A prospective follow-up analysis based on the
      ProGERD study.
AB  - BACKGROUND: Gastro-oesophageal reflux disease can be associated with extra
      oesophageal reflux disease such as chronic cough or laryngeal symptoms. The aim
      of this study was to analyse the clinical course of extra-oesophageal reflux
      disease in a large population with gastro-oesophageal reflux disease and extra
      oesophageal reflux disease under routine clinical care. METHODS: ProGERD is a
      prospective multicentre cohort study of 6215 outpatients with gastro-oesophageal
      reflux disease. At baseline all patients underwent endoscopies and were
      interviewed for extra-oesophageal reflux disease. Initial standardised treatment
      was esomeprazole for up to 8 weeks. After 2 years of follow-up, reflux symptoms
      and the prevalence of extra-oesophageal reflux disease were assessed. A
      multivariate analysis was performed with resolved versus persistent symptoms for
      chronic cough and laryngeal symptoms as dependent predictors. Independent
      variables were gender, age, body mass index (BMI), alcohol consumption, cigarette
      smoking, gastro-oesophageal reflux disease classification, history of gastro
      oesophageal reflux disease in the family, duration of gastro-oesophageal reflux
      disease and proton pump inhibitors medication. RESULTS: Four thousand four
      hundred and four patients (71%) were available for analysis at 2 years, including
      570 and 454 patients who had chronic cough and laryngeal disorders at baseline,
      respectively. In 63% and 74% of the patients, chronic cough and laryngeal
      disorders had resolved. Patients with persistent respiratory symptoms in year 2
      had significantly more reflux symptoms. Further clinically relevant associations
      were smoking and non-steroidal anti-inflammatory drugs use. According to the
      multivariate analysis, classification of gastro-oesophageal reflux disease,
      proton pump inhibitors medication or duration of gastro-oesophageal reflux
      disease were not associated with the resolution of cough or laryngeal symptoms.
      CONCLUSION: In most patients with gastro-oesophageal reflux disease and extra
      oesophageal reflux disease, respiratory symptoms resolve during long-term routine
      care. A high reflux symptom load was associated with the persistence of
      respiratory disorders.

PMID- 16413234
TI  - Geometry and cell density of rat craniofacial sutures during early postnatal
      development and upon in vivo cyclic loading.
AB  - Cranial sutures are unique to skull bones and consist of multiple connective
      tissue cell lineages such as mesenchymal cells, fibroblast-like cells, and
      osteogenic cells, in addition to osteoclasts. Mechanical modulation of
      intramembranous bone growth in the craniofacial suture is not well understood,
      especially during postnatal development. This study investigated whether in vivo
      mechanical forces regulate sutural growth responses in postnatal rats. Cyclic
      compressive forces with a peak-to-peak magnitude of 300 mN and 4 Hz were applied
      to the maxilla in each of 17-, 23-and 32-day-old rats for 20 min/day over 5
      consecutive days. Computerized histomorphometric analysis revealed that cyclic
      loading significantly increased the average geometric widths of the
      premaxillomaxillary suture (PMS) to 86 +/- 7 microm, 99 +/- 12 microm, and 149 +/
      30 microm, representing 32%, 50%, and 39% increases for P17, P23, and P32 in
      comparison with age-matched sham controls. For the nasofrontal suture (NFS),
      cyclic loading significantly increased the average sutural widths to 88 +/- 15
      microm, 92 +/- 10 microm, and 100 +/- 14 microm, representing 33%, 24%, and 32%
      increases for P17, P23, and P32 relative to age-matched controls. The average PMS
      cell density upon cyclic loading was 10182 +/- 132 cells/mm(2), 9752 +/- 661
      cells/mm(2), and 9521 +/- 628 cells/mm(2), representing 62%, 35%, and 30%
      increases for P17, P23, and P32 in comparison with age-matched controls. For the
      NFS, cyclic loading increased the average cell density to 9884 +/- 893
      cells/mm(2), 9818 +/- 1091 cells/mm(2), 9355 +/- 661 cells/mm(2), representing
      44%, 46% and 40% increases at P17, P23, and P32 respectively. Osteoblast-occupied
      sutural bone surface was significantly greater in cyclically loaded sutures for
      P17, P23, and P32 than corresponding controls for both the PMS and NFS. On the
      other hand, cyclic loading elicited significantly higher sutural bone surface
      populated by osteoclast-like cells by P17 and P23 days, but not P32 days, for the
      PMS. For the NFS, sutural osteoclast surface was significantly higher upon cyclic
      loading for P23 and P32 days, but not P17. The present data demonstrate that
      cyclic forces are potent stimuli for modulating postnatal sutural development,
      potentially by stimulating both osteogenesis and osteoclastogenesis. Cyclic
      loading may have clinical implications as novel mechanical stimuli for modulating
      craniofacial growth in patients suffering from craniofacial anomalies and
      dentofacial deformities.

PMID- 16413235
TI  - Osteoblast and osteocyte apoptosis associated with androgen action in bone:
      requirement of increased Bax/Bcl-2 ratio.
AB  - Both the number and the activity of osteoblasts are critical for normal bone
      growth and maintenance. Although a potential role for estrogen in protection of
      bone mass through inhibition of osteoblast apoptosis has been proposed, a
      function for androgen is much less clear. The aim of this study was to establish
      a direct role for androgen to influence osteoblast apoptosis both in vitro and in
      vivo. AR-MC3T3-E1 cells, with androgen receptor (AR) overexpression controlled by
      the type I collagen promoter, were treated with the non-aromatizable androgen
      5alpha-dihydrotestosterone (DHT). Apoptosis was assessed by three different
      techniques including DNA fragmentation, caspase-3 activation, and changes in
      mitochondrial membrane potential. Transactivation of AR by DHT enhanced apoptosis
      while 17beta-estradiol (E(2)) treatment reduced apoptosis in both proliferating
      preosteoblasts and mature osteocyte-like cells. To explore mechanism, the
      apoptosis regulators Bcl-2 (antiapoptotic) and Bax (proapoptotic) were evaluated.
      Western analysis revealed that DHT decreased Bcl-2 resulting in a significantly
      increased Bax/Bcl-2 ratio. Regulation of Bcl-2 was post-transcriptional since bcl
      2 mRNA levels were unaffected by DHT treatment. Furthermore, ubiquitination of
      Bcl-2 was increased and serine phosphorylation was reduced, consistent with
      inhibition of MAP kinase signaling by DHT. Increased Bax/Bcl-2 ratio was
      essential since either Bcl-2 overexpression or Bax downregulation by RNA
      interference (RNAi) partially abrogated or reversed DHT-enhanced osteoblastic
      apoptosis. In order to establish physiologic significance in vivo, AR-transgenic
      mice with AR overexpression in the osteoblast lineage and thus enhanced androgen
      sensitivity were characterized. In male AR-transgenic mice, increased osteoblast
      apoptosis was observed in vivo even in association with new bone formation. Thus,
      although estrogen can be antiapoptotic, androgen stimulates osteoblast and
      osteocyte apoptosis through an increased Bax/Bcl-2 ratio even in anabolic
      settings. These results identify a new mechanism for androgen regulation of
      osteoblast activity distinct from estrogen, and suggest that enhanced apoptosis
      can be associated with anabolic stimulation of new bone growth. Androgens thus
      play a distinct role in skeletal homeostasis.

PMID- 16413236
TI  - The 2005 Leon I. Goldberg Young Investigator Award Lecture: Development of
      thalidomide as an angiogenesis inhibitor for the treatment of androgen
      independent prostate cancer.

PMID- 16413237
TI  - New insights into the mechanism of action of acetaminophen: Its clinical
      pharmacologic characteristics reflect its inhibition of the two prostaglandin H2
      synthases.

PMID- 16413238
TI  - The endothelium, inflammation, and coagulation in sepsis.

PMID- 16413239
TI  - Recombinant human antithrombin inhibits thrombin formation and interleukin 6
      release in human endotoxemia.
AB  - We hypothesized that infusion of recombinant human antithrombin without
      concomitant heparin would have dose-dependent anticoagulant properties and
      potentially decrease endotoxin (lipopolysaccharide [LPS])-induced cytokine
      production. This was a randomized, double-blind, placebo-controlled study in
      parallel groups enrolling 30 healthy male volunteers. The active treatment groups
      received infusions of recombinant human antithrombin to increase antithrombin
      levels to 200% and 500% before infusion of 2 ng/kg endotoxin (LPS). Infusion of
      antithrombin dose-dependently decreased coagulation (P < .01 by repeated-measures
      ANOVA): peak levels of prothrombin fragment (1.8 nmol/L [95% confidence interval
      (CI), 1.3-2.3 nmol/L] in the 500% antithrombin group and 4.4 nmol/L [95% CI, 2.7
      6.2 nmol/L] in the placebo group at 4 hours), thrombin antithrombin complexes (12
      microg/L [95% CI, 8-16 microg/L] in the 500% antithrombin group and 34 microg/L
      [95% CI, 20-48 microg/L] in the placebo group at 4 hours), and D-dimer (0.2
      microg/L [95% CI, 0.1-0.2 microg/L] in the 500% antithrombin group and 0.5
      microg/L [95% CI, 0.4-0.7 microg/L] in the placebo group). Recombinant human
      antithrombin decreased peak interleukin-6 levels by 40% (222 pg/mL [95% CI, 148
      295 pg/mL] and 216 pg/mL [95% CI, 112-320 pg/mL] in the 500% and 200%
      antithrombin groups, respectively, versus 357 pg/mL [95% CI, 241-474 pg/mL] in
      the placebo group; P < .001 by ANOVA). Finally, infusion of recombinant human
      antithrombin rapidly and transiently decreased neutrophil counts (by 19% [95% CI,
      8%-30%] in the 500% antithrombin group versus 6% [95% CI, 1%-10%] in the placebo
      group, P = .002 by Kruskal-Wallis ANOVA) and monocyte counts (by 30% [95% CI, 16%
      44%] in the 500% antithrombin group and 18% [95% CI, 9%-28%] in the 200%
      antithrombin group versus 8% [95% CI, 5%-20%] in the placebo group, P = .04)
      before LPS challenge, indicating that recombinant human antithrombin directly
      interacts with these leukocyte subsets. In summary, recombinant human
      antithrombin dose-dependently inhibited tissue factor-triggered coagulation.
      Effects on leukocytes and inhibition of interleukin-6 release seem to represent
      specific pharmacodynamic properties of recombinant human antithrombin.

PMID- 16413240
TI  - Evidence for morphine-independent central nervous opioid effects after
      administration of codeine: contribution of other codeine metabolites.
AB  - OBJECTIVE: Our objective was to investigate whether codeine or one of its
      metabolites contributes substantially to central nervous effects independent from
      the cytochrome P450 (CYP) 2D6-mediated O-demethylation to morphine. METHODS:
      After oral administration of codeine, plasma concentrations of codeine and its
      metabolites, as well as pupil size as a measure of central nervous effects, were
      measured in 11 healthy volunteers representing poor, intermediate, extensive, and
      ultrarapid metabolizers for CYP2D6. Subsequently, the observed plasma morphine
      concentrations were mimicked by use of computerized morphine infusion, and the
      miotic effects were compared with those observed after codeine administration.
      The contribution of codeine, codeine-6-glucuronide, norcodeine, morphine,
      morphine-6-glucuronide, and normorphine to the miotic effects was analyzed by
      means of pharmacokinetic-pharmacodynamic modeling. RESULTS: The areas under the
      curve of the miotic effects after codeine were 1.7 +/- 2 times greater than after
      morphine (P <0.01). This contrasted to similar or even lower morphine
      concentrations after codeine than after morphine (area under the curve ratio, 0.5
      +/- 0.4; P =.21). A pharmacokinetic-pharmacodynamic fit of the miotic effects by
      use of morphine as the only active moiety was most significantly (P <.0001)
      improved when codeine-6-glucuronide as a second active moiety was added.
      CONCLUSION: CYP2D6-dependent formation of morphine does not explain exclusively
      the central nervous effects of codeine. Codeine-6-glucuronide is the most likely
      additional active moiety.

PMID- 16413241
TI  - Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor AVE7688 in
      humans.
AB  - OBJECTIVE: Our objective was to define the pharmacodynamic profile of the new
      dual neutral endopeptidase (NEP)/angiotensin-converting enzyme (ACE) inhibitor
      AVE7688. METHODS: We compared the effects of single oral doses of AVE7688 (5 and
      25 mg) with those of 10 mg ramipril (R10), a selective ACE inhibitor, in a
      placebo-controlled crossover study in sodium-depleted normotensive subjects. We
      also compared the effects of 25 mg AVE7688 with those of a renin-angiotensin
      system (RAS) blockade induced by a high dose of an angiotensin II receptor
      antagonist (300 mg irbesartan) and a dual blockade of the RAS (150 mg irbesartan
      plus 10 mg ramipril) in sodium-replete normotensive subjects by use of the same
      study design. The in vivo inhibition of ACE and NEP was monitored by measuring
      the urinary excretion of N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) and atrial natriuretic
      peptide (ANP), respectively. The intensity of RAS blockade was assessed by the
      increase in plasma active renin concentration. RESULTS: The 24-hour urine AcSDKP
      cumulative excretion increased significantly more after 25 mg AVE7688 (919 nmol
      [95% confidence interval (CI), 803-1052 nmol], P < .05) than after 5 mg AVE7688
      (706 nmol [95% CI, 612-813 nmol]) or 10 mg ramipril (511 nmol [95% CI, 440-593
      nmol]). The 25-mg dose of AVE7866 significantly and transiently (4 to 8 hours
      after drug intake) increased urinary ANP (2.02 +/- 1.05 ng/h, P < .05), whereas 5
      mg AVE7688 (1.14 +/- 0.77 ng/h) and 10 mg ramipril (0.93 +/- 0.65 ng/h) had no
      effect compared with placebo (0.80 +/- 0.37 ng/h). In the low-salt panel the rise
      in plasma active renin concentration achieved 24 hours after dosing by 25 mg
      AVE7688 (247 pg/mL [95% CI, 157-389 pg/mL], P < .05) was significantly higher
      than that achieved by 5 mg AVE7688 (129 pg/mL [95% CI, 75-221 pg/mL]) or 10 mg
      ramipril (113 pg/mL [95% CI, 67-193 pg/mL]), which did not differ. In the high
      salt panel group the effects of 25 mg AVE7688 on renin release did not
      significantly differ from those after administration of the combination of 150 mg
      irbesartan plus 10 mg ramipril or 300 mg irbesartan alone. All of these active
      drugs similarly decreased blood pressure compared with placebo. CONCLUSION:
      AVE7688 at a dose of 25 mg has a favorable pharmacodynamic profile compared with
      other RAS blockers. These results support further clinical studies of its long
      term effects in essential or resistant hypertension, chronic proteinuric
      nephropathy, and chronic heart failure.

PMID- 16413242
TI  - MDR1 gene polymorphisms and risk of gingival hyperplasia induced by calcium
      antagonists.
AB  - BACKGROUND: Gingival overgrowth is a common side effect of calcium antagonists.
      Although the pathogenesis is unknown, several lines of evidence point to a
      modulation of inflammatory processes. Because the calcium antagonists, albeit to
      a variable degree, act as inhibitors of P-glycoprotein (P-gp), the gene product
      of multidrug resistance 1 (MDR1), and inflammation may modify P-gp expression, we
      analyzed the MDR1 polymorphisms as risk factors for gingival overgrowth induced
      by calcium antagonists. METHODS: Clinical, laboratory, and anamnestic data
      including periodontal parameters and use of calcium antagonists were assessed in
      a cross-sectional epidemiologic investigation (N = 1484). MDR1 polymorphisms in
      exon 21 G2677T/A and exon 26 C3435T were determined. P-gp expression was detected
      in gingival tissues. In a matched-pair analysis, 93 subjects using calcium
      antagonists and 186 not using them were compared. RESULTS: P-gp is expressed in
      the endothelial layers of blood vessels obtained from healthy or inflamed
      gingiva. Subjects treated with calcium antagonists had significantly deeper
      gingival pockets than their drug-free counterparts (P <.0001). This drug-related
      side effect was associated with the MDR1 2677G/G or G/TA genotype (P <.001) but
      not with the variant genotype T/TA. This drug effect was proved by multiple
      regression analysis with adjustment for the risk factors of periodontitis (age,
      sex, smoking, and education) (P <.0001) and was associated with elevated C
      reactive protein levels. The association of probing depth with the MDR1
      polymorphism was confirmed in the matched-pair analysis (P <.0001). CONCLUSION:
      Treatment with calcium antagonists leads to gingival hyperplasia, which is
      associated with the MDR1 G2677T/A polymorphism. The MDR1 genotype may modify the
      inflammatory response to the drugs.

PMID- 16413243
TI  - Modulation of the central nervous effects of levomethadone by genetic
      polymorphisms potentially affecting its metabolism, distribution, and drug
      action.
AB  - AIM: Our aim was to judge the importance of candidate pharmacogenetic modulators
      of the central nervous effects of levomethadone by both magnitude of the
      modulatory effect and frequency of the mutation to assess the utility of
      genotyping for clinical levomethadone therapy in a random sample of subjects
      that, by distribution of genotypes, resembled the clinical setting. METHODS:
      Candidate pharmacogenetic modulators were polymorphisms reported to be of
      functional consequence and therefore potentially important for metabolism,
      distribution, or pharmacodynamic action of levomethadone, consisting of genes
      coding for cytochrome P450 (CYP) 2B6 and 3A, as well as 1A2, 2C8, 2C9, 2C19, and
      2D6, for P-glycoprotein (ABCB1), and for mu-opioid receptors (OPRM1). The central
      nervous effects of levomethadone were investigated by means of measuring pupil
      size in a random sample of 51 healthy volunteers for 9 hours after oral
      administration of 0.075 mg/kg levomethadone. Plasma concentrations of
      levomethadone and its metabolites were assessed concomitantly, and to judge the
      role of metabolites, the affinities of levomethadone and its metabolites at mu
      opioid receptors were estimated by use of displacement of the selective mu-opioid
      receptor agonist [(3)H]-DAMGO ((3)H-[D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin).
      RESULTS: Pupil size decreased to -41.8% +/- 9.6% from baseline at 3.5 +/- 1.1
      hours after levomethadone administration. Miosis was still manifest to a lower
      degree (-25.1% +/- 12.3%) at the end of the observation period. In carriers of
      the variant 118G allele (118A>G single-nucleotide polymorphism) of the mu-opioid
      receptor gene (OPRM1), levomethadone had a 1.74 times (95% confidence interval,
      1.4-2.2 times) lower miotic potency (P < .001) as compared with noncarriers
      (concentration at half-maximum effects, 52.3 nmol/L; 95% confidence interval,
      36.7-66.2 nmol/L). The maximum percent decrease in pupil diameter from baseline
      was 44.9% +/- 7.6%, 33% +/- 6.5%, and 24% +/- 6.9% for carriers of the OPRM1
      118AA, AG, and GG genotypes, respectively (P < .001 for AG and GG versus wild
      type, without significant differences between AG and GG). Other candidate
      polymorphisms in the ABCB1 or in CYP genes had no significant influence on the
      effects of levomethadone, either because of lack of functional consequences or
      because of their low allelic frequency. The metabolites of levomethadone did not
      contribute to the effects as indicated by low metabolite plasma concentrations
      and their 120- to 1300-fold lower affinities at mu-opioid receptors as compared
      with levomethadone. CONCLUSIONS: Among polymorphisms in OPRM1, ABCB1, and CYP
      genes previously associated with functional consequences in a different context,
      the most important pharmacogenetic factor modulating the short-term effects of
      levomethadone is a polymorphism (OPRM1 118A>G) affecting mu-opioid receptors.

PMID- 16413244
TI  - Intestinal MDR1/ABCB1 level at surgery as a risk factor of acute cellular
      rejection in living-donor liver transplant patients.
AB  - BACKGROUND: Although the prevention of immunologic reactions with sufficient
      immunosuppression prolongs graft and patient survival rates, the large
      interindividual variation in tacrolimus pharmacokinetics interferes with
      treatment. In this study we have examined whether intestinal MDR1 (ABCB1) is a
      potential biomarker predicting the occurrence of acute cellular rejection, as
      well as a factor to predict absorption of tacrolimus, after living-donor liver
      transplantation. METHODS: By use of tissue specimens of intestinal mucosa (n =
      164) obtained at surgery, the messenger ribonucleic acid (mRNA) expression of
      intestinal MDR1 and cytochrome P450 (CYP) 3A4 was quantified. RESULTS: The
      probability of acute cellular rejection during the first 10 days after surgery
      was significantly associated with the average trough concentration of tacrolimus
      between postoperative days 2 and 4 (45.1% for <7 ng/mL versus 22.9% for >7
      ng/mL,P= .0040). High levels of MDR1 were associated with an episode of acute
      cellular rejection before postoperative day 10 (odds ratio, 2.306 [95% confidence
      interval, 1.058-5.028]) and with a poor survival rate during the first
      postoperative year (odds ratio, 7.413 [95% confidence interval, 1.567-36.073]).
      The mRNA expression level of MDR1 was inversely correlated with the tacrolimus
      concentration-oral dose ratio during the initial 4 days after surgery in patients
      with a graft-to-recipient weight ratio greater than 1.5 (r= -0.6798, P< .0001)
      and those with a graft-to-recipient weight ratio of less than 1.5 (r= -0.7180, P<
      .0001). CONCLUSION: The enterocyte MDR1 mRNA level was suggested to be a risk
      factor for acute cellular rejection and death after surgery. Therefore obtaining
      a sufficient tacrolimus blood level via this molecular information-based initial
      dosage adjustment may enable the episode of acute cellular rejection after liver
      transplantation to be reduced.

PMID- 16413245
TI  - A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant
      for the drug response to proton pump inhibitors and antidepressants.
AB  - BACKGROUND AND OBJECTIVE: Many drugs, including proton pump inhibitors and
      certain antidepressants, are metabolized by the polymorphic cytochrome P450 (CYP)
      2C19 enzyme. A significant portion of extensive metabolizers do not reach
      appropriate drug levels, and our objective was to investigate any genetic
      background. METHODS: The 5'-flanking region of the CYP2C19 gene from subjects
      with rapid omeprazole metabolism was sequenced, and CYP2C19 phenotype-genotype
      associations were analyzed in Swedish (n = 107) and Ethiopian (n = 126) extensive
      metabolizers. The relationship of the metabolic ratio of omeprazole (omeprazole/5
      hydroxyomeprazole in plasma 3 hours after drug intake) with the area under the
      plasma concentration-time curve was used for prediction studies. Electrophoretic
      mobility shift assays were conducted by use of human nuclear protein extracts.
      Hepatic reporter vector transfections were carried out in CD1 mice. RESULTS: We
      identified a novel allele (CYP2C19*17) carrying -806C>T and -3402C>T, with a
      frequency of 18% in both Swedes and Ethiopians and 4% in Chinese subjects. In
      Swedes the metabolic ratio of omeprazole was higher in subjects homozygous for
      CYP2C19*1 (median, 0.50 [interquartile range, 0.37-0.73]) than in those
      homozygous for CYP2C19*17 (median, 0.25 [interquartile range, 0.15-0.33]) (P =
      .010). In Ethiopians a similar difference in the S/R-mephenytoin ratio was
      observed between individuals homozygous for CYP2C19*1 (median, 0.20
      [interquartile range, 0.12-0.37]) and those homozygous for CYP2C19*17 (median,
      0.05 [interquartile range, 0.03-0.06]) (P = .013). Electrophoretic mobility shift
      assays showed specific binding of human hepatic nuclear proteins to an element
      carrying -806T but not -806C. Reporter vector experiments showed an increased
      transcriptional activity of the CYP2C19*17 allele in vivo in mice. Predictions
      revealed that CYP2C19*17 homozygotes would attain 35% to 40% lower omeprazole
      area under the plasma concentration-time curve values than subjects homozygous
      for CYP2C19*1 taking standard doses of omeprazole. CONCLUSION: CYP2C19*17 is
      likely to cause therapeutic failures in drug treatment with, for example, proton
      pump inhibitors and antidepressants.

PMID- 16413246
TI  - Population analyses of amlodipine in patients living in the community and
      patients living in nursing homes.
AB  - OBJECTIVE: Our objective was to determine the effects of age, sex, and morbidity
      on the apparent oral clearance (CL/F) of amlodipine. METHODS: Population
      pharmacokinetic analyses were performed on data from 211 patients receiving oral
      racemic amlodipine (dose of 7.2 +/- 3.6 mg/d [mean +/- SD]) on a long-term basis.
      Of the patients, 105 were men, with a mean age of 72 +/- 13 years and lean body
      weight (LBW) of 60.7 +/- 7.6 kg, and 106 were women, with a mean age of 79 +/- 11
      years and LBW of 44.2 +/- 6.0 kg; 119 lived in the community, 20 in assisted
      living facilities, and 72 in nursing homes. Amlodipine was measured by liquid
      chromatography-tandem mass spectrometry. Population analyses were performed by
      use of NONMEM with sex, age, race, living site, alcohol intake, and concomitant
      medications considered as covariates. The significance of covariates was
      determined by likelihood ratio tests. RESULTS: Female sex and living in a nursing
      home were associated with a faster CL/F compared with men and community-dwelling
      patients, respectively. The mean CL/F was 7.83 +/- 0.50 mL.min(-1).kg(-1) (LBW)
      in women compared with 6.31 +/- 1.01 in men and 8.68 +/- 1.00 mL.min(-1).kg(-1)
      in nursing home residents compared with 6.32 +/- 1.17 in community-dwelling
      patients. Increasing age was associated with decreasing CL/F only in community
      dwelling patients and residents of assisted living facilities. CONCLUSIONS: In
      middle-aged and very old (>80 years) patients, amlodipine CL/F was faster in
      women compared with men and was faster in nursing home residents compared with
      community-dwelling patients, with increasing age decreasing CL/F only in
      community-dwelling patients and residents of assisted-living facilities.

PMID- 16413247
TI  - Interaction of flurbiprofen with cranberry juice, grape juice, tea, and
      fluconazole: in vitro and clinical studies.
AB  - OBJECTIVES: Recent anecdotal, unvalidated case reports have suggested
      potentiation of warfarin-induced anticoagulation by cranberry juice, possibly
      through inhibition of human cytochrome P450 (CYP) 2C9, the enzyme responsible for
      the clearance of the active S-enantiomer of warfarin. To address this question,
      the effect of cranberry juice and other beverages on CYP2C9 activity was
      evaluated in vitro and in vivo. METHODS: The effects of 4 beverages on CYP2C9
      activity were studied in human liver microsomes, by use of flurbiprofen
      hydroxylation as the index reaction. In a clinical study 14 healthy volunteers
      received 100 mg flurbiprofen on 5 occasions in a crossover fashion, with at least
      1 week separating the 5 trials. Flurbiprofen was preceded in random sequence by
      the following: (1) cranberry juice placebo (8 oz), (2) cranberry juice (8 oz),
      (3) brewed tea (8 oz), (4) grape juice (8 oz), and (5) fluconazole, a CYP2C9
      inhibitor serving as a positive control, with 8 oz of water. RESULTS: Flubiprofen
      hydroxylation in vitro was reduced to 11% +/- 8% of control by 2.5% (vol/vol)
      brewed tea, to 10% +/- 7% of control by grape juice, to 56% +/- 16% of control by
      cranberry juice, to 85% +/- 5% of control by cranberry juice placebo, and to 21%
      +/- 6% of control by the index inhibitor sulfaphenazole (2.5 micromol/L) (P <.01
      for all comparisons versus control). Flurbiprofen clearance (29-33 mL/min) and
      elimination half-life (3.3-3.4 hours) did not differ significantly among trials
      1, 2, 3, and 4. However, clearance in the fluconazole treatment condition (trial
      5) was significantly reduced compared with the placebo control (17 +/- 5 mL/min
      versus 31 +/- 8 mL/min, P <.05), and the half-life was prolonged (5.3 +/- 1.6
      hours versus 3.3 +/- 0.8 hours, P <.05). Formation of 4-hydroxyflurbiprofen was
      correspondingly reduced by fluconazole (P <.05). CONCLUSIONS: Although grape
      juice and tea impaired CYP2C9 activity in vitro, none of the 3 beverages altered
      CYP2C9-mediated clearance of flurbiprofen in humans, making a pharmacokinetic
      interaction with warfarin highly unlikely.

PMID- 16413248
TI  - Pharmacokinetic study of memantine in healthy and renally impaired subjects.
AB  - OBJECTIVE: Our objective was to evaluate the pharmacokinetics of the Alzheimer's
      disease treatment memantine in subjects with normal and impaired renal function.
      METHODS: This was a single-center, single-dose, open-label study. Thirty-two
      subjects aged 18 to 80 years were assigned to 1 of 4 groups (8 subjects each)
      based on baseline creatinine clearance: normal renal function (>80 mL/min), mild
      renal impairment (50-80 mL/min), moderate renal impairment (30-49 mL/min), and
      severe renal impairment (5-29 mL/min). A single 20-mg memantine dose was
      administered under fasting conditions. Assessments included pharmacokinetic and
      safety measures. RESULTS: Thirty-one subjects completed the study. There were no
      relevant differences in maximum memantine plasma concentration between subjects
      with normal and impaired renal function of any severity. The mean area under the
      plasma concentration versus time curve extrapolated to infinity was similar
      between subjects with normal and mildly impaired renal function but increased by
      60% (95% confidence interval [CI], 24%-97%) and 115% (95% CI, 77%-152%) in
      subjects with moderate and severe renal impairment, respectively. Simulations
      predicted steady-state maximum concentration values of 82 ng/mL (95% CI, 70-95
      ng/mL), 85 ng/mL (95% CI, 70-101 ng/mL), and 128 ng/mL (95% CI, 109-147 ng/mL) in
      healthy subjects, those with mild renal impairment, and those with moderate renal
      impairment, respectively, for the recommended dosing regimen of 10 mg twice
      daily; for subjects with severe renal impairment, a steady-state maximum
      concentration value of 84 ng/mL (95% CI, 68-101 ng/mL) was predicted for a dosing
      regimen of 5 mg twice daily. CONCLUSION: On the basis of the predicted steady
      state plasma concentrations with the use of the current dosing regimen of 10 mg
      twice daily, no dosage adjustments are needed for patients with mild or moderate
      renal impairment. A target dose of 5 mg twice daily is recommended in patients
      with severe renal impairment.

PMID- 16413249
TI  - Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced
      and standard doses: a crossover comparative study in homozygous extensive
      metabolizers of cytochrome P450 2C19.
AB  - BACKGROUND AND OBJECTIVES: To improve clinical outcomes of the initial therapy
      for gastroesophageal reflux disease, intragastric pH should be above 4.0 for more
      than 20 hours a day (83.3%) and nocturnal gastric acid breakthrough, defined as
      60 continuous minutes of intragastric pH below 4.0 at night, should be inhibited.
      A "step-down" therapy sometimes fails because of insufficient acid suppression.
      Therefore we compared the acid-suppressive effects of proton pump inhibitors.
      METHODS: This was a prospective, randomized, open-label, 8-way crossover study.
      In 9 healthy Helicobacter pylori-negative cytochrome P450 (CYP) 2C19 homozygous
      extensive metabolizers, intragastric pH was measured for 24 hours on day 7 of
      treatment with rabeprazole, omeprazole, and lansoprazole orally administered once
      daily at reduced and standard doses. RESULTS: Compared with baseline data (7%
      [range, 5%-20%]), the median values of the 24-hour percent of time that
      intragastric pH was above 4.0 significantly increased but did not exceed 83.3%
      under any of the 7 regimens, which were as follows: 10 mg rabeprazole (51%
      [range, 28%-78%], P < .01), 20 mg rabeprazole (59% [range, 36%-83%], P < .01), 10
      mg omeprazole (26% [range, 4%-33%], P < .05), 20 mg omeprazole (48% [range, 31%
      73%], P < .01), 40 mg omeprazole (62% [range, 47%-87%], P < .01), 15 mg
      lansoprazole (34% [range, 5%-51%], P < .05), and 30 mg lansoprazole (56% [range,
      20%-76%], P < .05). Significant differences were observed among 10, 20, and 40 mg
      omeprazole (10 mg versus 20 mg, P < .01; 10 mg versus 40 mg, P < .01; and 20 mg
      versus 40 mg, P < .05) and between 15 and 30 mg lansoprazole (P < .01), whereas
      no significant difference was observed between 10 and 20 mg rabeprazole.
      Nocturnal gastric acid breakthrough was observed under all regimens. CONCLUSIONS:
      Rabeprazole, omeprazole, and lansoprazole, given once daily at standard doses,
      cannot be expected to achieve ideal acid suppression for the initial therapy for
      gastroesophageal reflux disease in Helicobacter-negative CYP2C19 homozygous
      extensive metabolizers. Rabeprazole 10 mg may be appropriate for step-down
      therapy.

PMID- 16413250
TI  - Television-the ideal idol for the idle?

PMID- 16413252
TI  - Arrays of transfected mammalian cells for high content screening microscopy.
AB  - In this chapter we describe protocols for reverse transfection to generate
      mammalian cell arrays for systematic gene knock-downs by RNAi or knock-ins by
      ectopic cDNA expression. The method is suitable for high content screening
      microscopy at a high spatial and temporal resolution allowing even time-lapse
      analysis of hundreds of samples in parallel.

PMID- 16413253
TI  - Imaging platforms for measurement of membrane trafficking.
AB  - In this chapter we describe automated imaging methods used to measure the
      transport of an established membrane transport marker from the endoplasmic
      reticulum to the plasma membrane. The method is fast and significantly robust to
      be applied in systematic studies on a large scale such as genome-wide screening
      projects. We further describe the use of software macros and plugins in Image J
      that allow the quantification of the kinetics of membrane transport intermediates
      in fluorescence microscopy time-lapse sequences.

PMID- 16413254
TI  - Bioinformatic "Harvester": a search engine for genome-wide human, mouse, and rat
      protein resources.
AB  - Harvester is a meta search engine for gene and protein information. It searches
      16 major databases and prediction servers and combines the results on
      pregenerated HTML pages. In this way Harvester can provide comprehensive gene
      protein information from different servers in a convenient and fast manner. The
      Harvester search engine works similar to Google, offering genome-wide ranked
      results at very high speed. Here we describe how to use this bioinformatic tool
      along with selected examples.

PMID- 16413255
TI  - Microinjection as a tool to explore small GTPase function.
AB  - Microinjection overcomes the plasma membrane barrier to the introduction of
      charged or large nonlipid soluble molecules into cells by the direct insertion of
      a hollow capillary micropipette into the cell. With the application of pressure,
      aqueous solution is then directly transferred into either the cytosol or the
      nucleus. I give specific examples of the application of this approach to the
      functional study of small GTPases of the Sar1, ARF, and rab family in membrane
      trafficking between the Golgi apparatus and endoplasmic reticulum (ER). The
      principles illustrated by these examples should be generally applicable to other
      small GTPases. Detailed protocols for capillary microinjection using
      semiautomated equipment are given.

PMID- 16413256
TI  - Visualizing intracellular events in vivo by combined video fluorescence and 3-D
      electron microscopy.
AB  - The combination of the capability of in vivo fluorescence video microscopy with
      the power of resolution of electron microscopy (EM) has been described. This
      approach is based on such an association of two techniques. An individual
      intracellular structure can be monitored in vivo, typically through the use of
      markers fused with green fluorescent protein (GFP), and a "snapshot" of its three
      dimensional (3-D) ultrastructure and especially tomographic reconstruction can
      then be taken at any chosen time during its life cycle. The pitfalls and
      potential of this approach are discussed.

PMID- 16413257
TI  - Recombinant production in baculovirus-infected insect cells and purification of
      the mammalian Sec13/Sec31 complex.
AB  - Membrane traffic along the eukaryotic secretory pathway starts with the selective
      packing of biosynthetic cargo into nascent vesicles that are forming on the
      endoplasmic reticulum (ER). This process is mediated by the coat protein complex
      II (COPII) machinery, which at the minimum, comprises the Sar1 GTPase and the
      cytosolic protein complexes Sec23/Sec24 (Sec23/24) and Sec13/Sec31 (Sec13/31).
      While the components of the basic COPII machinery are highly conserved from yeast
      to human, it is now clearly evident that the overall process is under tighter
      spatial and temporal regulation in higher eukaryotes. Here we describe
      recombinant production in baculovirus-infected insect cells and subsequent
      purification to homogeneity of the mammalian Sec13/31 complex for biochemical and
      biophysical characterization.

PMID- 16413258
TI  - Purification and properties of mammalian Sec23/24 from insect cells.
AB  - The Sec23/24 complex is a large heterodimeric protein involved in COPII vesicle
      biogenesis. The individual mammalian protein subunits are too large for
      expression in bacterial systems. This article details the use of the Bac-to-Bac
      baculovirus coexpression system in insect cells for both the human Sec23A and
      Sec24C. This strategy results in high yields of pure, functional protein and can
      be adapted for the purification of other Sec23/24 isoforms for their biochemical
      and biological characterization.

PMID- 16413259
TI  - Purification and functional properties of yeast Sec12 GEF.
AB  - In order to reconstitute the generation of COPII vesicles from synthetic
      liposomes, the minimum requirements are the coat components, Sar1p GTPase,
      Sec23/24p, Sec13/31p, and a nonhydrolyzable GTP analog such as GMP-PNP. However,
      in the presence of GTP, nucleotide hydrolysis by Sar1p renders the coat
      insufficiently stable to sustain vesicle budding. Sar1p GTPase activity was
      activated by the Sec23/24p GTPase-activating protein (GAP), and further
      accelerated 10-fold by Sec13/31p. In order to study GTP-dependent budding, we
      introduced the Sar1p guanine nucleotide exchange factor (GEF), Sec12p. We
      evaluated Sar1p activation by Sec12p and the dynamics of coat assembly and
      disassembly in the presence of both Sec12p and Sec23/24p. The cytoplasmic domain
      of Sec12p activated Sar1p with a turnover 10-fold higher than the GAP activity of
      Sec23p in the presence of Sec13/31p. As a result, the entire COPII coat remains
      stable in the presence of GTP. Here, we describe methods to purify Sec12p, real
      time fluorescence assays to evaluate COPII coat formation, and the relevant
      kinetic analyses.

PMID- 16413260
TI  - Reconstitution of cargo-dependent COPII coat assembly on proteoliposomes.
AB  - The coat protein complex II (COPII) coat is responsible for direct capture of
      membrane cargo proteins and for the physical deformation of the endoplasmic
      reticulum (ER) membrane that drives the transport vesicle formation. The use of
      an in vitro reconstitution system comprising purified components is desirable for
      studies aimed at elucidating the role(s) of individual proteins in a specific
      biochemical reaction. To investigate the assembly-disassembly of COPII coats in a
      completely reconstituted reaction, we have developed a synthetic budding reaction
      involving purified coat proteins and cargo-reconstituted proteoliposomes. We
      describe here a fluorescence resonance energy transfer (FRET)-based method for
      monitoring the kinetics of COPII coat complex assembly and disassembly in cargo
      reconstituted proteoliposomes. This assay allows comparison of the time course of
      the coat disassembly from the cargo as monitored by FRET signal with the time
      course of accompanying Sar1p GTP hydrolysis by tryptophan fluorescence.

PMID- 16413261
TI  - Real-time assays for the assembly-disassembly cycle of COP coats on liposomes of
      defined size.
AB  - The assembly-disassembly cycle of COPI and COPII coats is controlled by the
      GTPase cycle of the small G proteins Arf1 and Sar. We describe here two
      spectroscopic assays that enable real-time studies of some elementary steps of
      coat assembly and disassembly on artificial liposomes of defined composition and
      curvature. A flotation assay to assess the effect of membrane curvature on
      protein adsorption to liposomes is also presented.

PMID- 16413262
TI  - Assay and measurement of phospholipase D activation by Sar1.

PMID- 16413263
TI  - Use of acyltransferase inhibitors to block vesicular traffic between the ER and
      Golgi complex.
AB  - This article describes the use of acyltransferase inhibitors as probes for
      studying the potential role of lysophospholipid acyltransferases (LPAT) in
      intracellular membrane trafficking in the secretory and endocytic pathways. The
      small molecule inhibitors that are described here were originally found as acyl
      CoA:cholesterol acyltransferase (ACAT) inhibitors. One of these, CI-976 (2,2
      methyl-N-(2,4,6,-trimethoxyphenyl)dodecanamide), was also found to be a potent
      LPAT inhibitor. CI-976 is a small, hydrophobic, membrane-permeant compound and
      both in vivo and in vitro studies have shown that it, but not other ACAT
      inhibitors, has a profound effect on multiple membrane trafficking pathways in
      eukaryotic cells including: (1) inhibition of COPII vesicle budding from the
      endoplasmic reticulum (ER), (2) inhibition of transferrin and transferrin
      receptor export from the endocytic recycling compartment, and (3) stimulation of
      tubule-mediated retrograde trafficking of Golgi membranes to the ER. Here we
      describe the use of CI-976 and other ACAT inhibitors for studies with both
      cultured mammalian cells and in vitro reconstitution assays, with a particular
      emphasis on COPII vesicle budding from the ER. All of these studies strongly
      suggest that CI-976-sensitive LPATs play a role in coated vesicle fission, and
      therefore, CI-976 is a valuable addition to the arsenal of small molecule
      inhibitors that can be used to study secretory and endocytic membrane trafficking
      pathways.

PMID- 16413264
TI  - Tethering assays for COPI vesicles mediated by golgins.
AB  - A method is described that allows the attachment of COPI vesicles and Golgi
      membranes to glass slides that can then be analyzed using electron microscopy
      (EM) and immuno-EM methods. Subpopulations of COPI vesicles can be bound
      selectively using recombinant golgins. Alternatively, COPI vesicles can be
      attached to prebound Golgi membranes. Marking these vesicles selectively with
      biotin allows their site of attachment to be identified.

PMID- 16413265
TI  - Investigating the role of ADP-ribosylation factor 6 in tumor cell invasion and
      extracellular signal-regulated kinase activation.
AB  - Tumor cell invasion is a coordinated process involving the formation of
      invadopodia and the localized degradation of the extracellular matrix (ECM). The
      process of cell invasion is regulated by cell-signaling proteins such as Ras
      related GTPases and members of the mitogen-activated protein kinase (MAPK)
      family. Our studies have focused on the role of the ADP-ribosylation factor 6
      (ARF6) GTPase in the process of tumor cell invasion. Using activated and dominant
      negative mutants of ARF6 in a tumor cell culture model, our laboratory has
      demonstrated that the GTPase cycle of ARF6 regulates invadopodia formation and
      matrix degradation. Furthermore, ARF6-mediated cell invasion was found to be
      dependent on the activation of the extracellular signal-regulated kinase (ERK).
      These findings demonstrate a critical role for ARF6 in ERK activation and tumor
      cell invasion. To investigate the role of ARF6 in tumor cell invasion and ERK
      activation, a number of methods were employed. These procedures include
      transfection of LOX cells, in vitro matrix-degradation assays, immunofluorescence
      microscopy, and biochemical assays. These approaches can be applied effectively
      to measure the degree of invasiveness fostered by ARF6 and/or other GTPases and
      to examine the subcellular distribution of the molecular players that are
      trafficked or recruited to sites of cell invasion.

PMID- 16413266
TI  - Assays and properties of the Arf GAPs AGAP1, ASAP1, and Arf GAP1.
AB  - ADP-ribosylation factors (Arfs) are Ras-like GTP-binding proteins that regulate
      membrane traffic and actin remodeling. Arf function requires GTP hydrolysis but
      Arf lacks GTPase activity; consequently, Arf function is dependent on Arf GTPase
      activating proteins (GAPs). The Arf GAPs are a structurally diverse group of at
      least 16 proteins. Several Arf GAPs use a single Arf isoform. However, due to
      structural differences, the conditions supporting productive interactions between
      Arf and different Arf GAPs vary. Here, we describe preparation and basic
      properties of three Arf GAPs. We use these proteins to illustrate assays for Arf
      GAP activity. Conditions that optimize activity for each GAP are discussed. These
      methods can be used for the further characterization of Arf-Arf GAP interaction
      that is necessary for understanding the function of Arf in cellular physiology.

PMID- 16413267
TI  - Preparation of myristoylated Arf1 and Arf6.
AB  - Arf proteins are members of the Arf family of small Ras-like GTP binding
      proteins. Six Arfs, grouped into three classes, have been identified in mammalian
      cells and three members have been identified in yeasts. Arf1 and Arf6, more
      extensively studied than other Arfs, have been found to affect membrane traffic
      and actin remodeling. A structural feature that distinguishes Arfs from other Ras
      superfamily members is an N-terminal alpha-helix, extending from the basic G
      protein fold, which is cotranslationally myristoylated. Both the helix and the
      myristate affect biochemical properties of Arfs, including nucleotide exchange,
      membrane association, and interaction with some effector proteins. Preparation of
      myristoylated Arf for in vitro studies of Arf function requires consideration of
      both the reaction yielding myristoylated protein and the properties of the
      modified Arfs. Here, we describe methods that yield homogeneous preparations of
      myristoylated Arf1 and Arf6.

PMID- 16413268
TI  - BIG1 and BIG2, brefeldin A-inhibited guanine nucleotide-exchange factors for ADP
      ribosylation factors.
AB  - BIG1 and BIG2 are large (approximately 200 kDa) guanine nucleotide-exchange
      proteins for ADP-ribosylation factors, or ARFs, that were isolated based on
      sensitivity of their guanine nucleotide-exchange activity to inhibition by
      brefeldin A. The intracellular distributions of BIG1 and BIG2 differ from those
      of other ARF guanine nucleotide-exchange proteins. In addition to its presence in
      Golgi membranes, BIG2 is seen in peripheral vesicular structures that most likely
      represent recycling endosomes, and BIG1 is found in nuclei of serum-starved HepG2
      cells. Several binding partners for BIG1 and BIG2 that were identified via yeast
      two-hybrid screens include FKBP13 and myosin IXb for BIG1 and, for BIG2, the
      regulatory RIalpha subunit of protein kinase A, Exo70, and the GABA receptor beta
      subunit. Autosomal recessive periventricular heterotopia with microcephaly, a
      disorder of human embryonic development due to defective vesicular trafficking,
      has been attributed to mutations in BIG2. Methods for purification of BIG1 and
      BIG2 from HepG2 cells are presented here, along with a summary of information
      regarding their structure and function.

PMID- 16413269
TI  - Cytohesin-1: structure, function, and ARF activation.
AB  - Mammalian cytohesins are a family of very similar guanine nucleotide-exchange
      proteins (GEPs) that activate ADP-ribosylation factors (ARFs). Cytohesins are
      multifunctional molecules comprising a Sec7 domain that is responsible for the
      GEP activity, a PH domain that binds specific phosphatidylinositol phosphates,
      and a coiled-coil domain responsible for homodimerization and interaction with
      other proteins. Cytohesin proteins are ubiquitous and have been implicated in
      several functions including cell spreading and adhesion, chemotaxis, protein
      trafficking, and cytoskeletal rearrangements, only some of which appear to depend
      on their ability to activate ARFs. Unlike the GEP activity of BIG1 and BIG2, the
      acceleration by cytohesins of guanine nucleotide exchange to generate active ARF
      GTP is not inhibited by the fungal metabolite brefeldin, A (BFA). This chapter is
      concerned for the most part with cytohesin-1 and the assay of its GEP activity.

PMID- 16413270
TI  - ADP-ribosylation factor domain protein 1 (ARD1), a multifunctional protein with
      ubiquitin E3 ligase, GAP, and ARF domains.
AB  - ADP-ribosylation factor domain protein 1 (ARD1) is a multifunctional protein that
      belongs to the family of 20-kDa ARF proteins. The ARD1 gene encodes a 64-kDa
      protein with a structure comprising an 18-kDa ADP-ribosylation factor (ARF)
      domain at the C-terminus (amino acids 403-574), and a 46-kDa N-terminal domain
      (amino acids 1-402) that contains, from the translation start site, a RING finger
      domain, two predicted B-Boxes, and a coiled-coil protein interaction motif, which
      places it among the TRIM (tripartite motif) or RBCC (RING, B-Box, coiled-coil)
      protein families. Recombinant ARD1 (amino acids 1-574) or its RING finger domain
      (amino acids 1-110) produced polyubiquitylated proteins when incubated in vitro
      with a mammalian E1, an E2 enzyme (UbcH6 or UbcH5a, -5b, or -5c), ATP, and
      ubiquitin. Via its C-terminal ARF domain, recombinant ARD1 binds guanine
      nucleotides, through which it can enhance, in a GTP-dependent manner, cholera
      toxin ADP-ribosyltransferase activity. Unlike ARFs, ARD1, but not its ARF domain,
      exhibits significant GTPase activity. Hydrolysis of GTP bound to the C-terminal
      ARF domain was stimulated by addition of the 46-kDa N-terminal domain (amino
      acids 1-402) via its GTPase activating protein (GAP) activity. The rate of GDP
      dissociation from the C-terminal ARF domain in ARD1, is slowed by the adjacent 15
      amino acids, which act as a GDP-dissociation inhibitor (GDI) domain. Cytohesin-1,
      known already as a guanine nucleotide-exchange factor (GEF) ARF activator, also
      specifically activated recombinant human ARD1, via activation of the ARF domain.
      Overexpressed ARD1 fusion proteins were associated with structures resembling
      lysosomes and Golgi membranes, as well as the nucleus, in different types of
      cells, and sequences potentially responsible for the intracellular localizations
      were identified.

PMID- 16413271
TI  - Expression of BIG2 and analysis of its function in mammalian cells.
AB  - BIG2 is a member of brefeldin A-inhibited guanine nucleotide exchange factors for
      ADP-ribosylation factors (ARFs). Although BIG2 is associated mainly with the
      trans-Golgi network, we have recently revealed that some population of BIG2 is
      associated with the recycling endosome. Moreover, we have found that expression
      of a catalytically inactive BIG2 mutant, E738K, selectively induces membrane
      tubules from this compartment. We have also demonstrated that the exchange
      activity of BIG2 is specific for class I ARFs (ARF1 and ARF3) in vivo and
      inactivation of either ARF enhances the BIG2(E738K)-induced membrane tubulation.
      Therefore, we have proposed that BIG2 is implicated in the structural integrity
      of the recycling endosome through activating class I ARFs. This article describes
      methods used for examining the function of BIG2 including basic protocols, which
      are not conventional because of cytotoxicity of BIG2 in Escherichia coli cells
      and its low expression efficiency in mammalian cells.

PMID- 16413272
TI  - Assays and properties of the ArfGAPs, AMAP1 and AMAP2, in Arf6 function.
AB  - The GTPase-activating protein (GAP) domain for Arfs primarily consists of a zinc
      finger structure, which is not present in known GAPs for the other Ras
      superfamily GTPases. More than 20 genes have been found to encode proteins
      bearing the ArfGAP domain in the human genome: a number that is much larger than
      that of the Arf isoforms. Several Arf isoforms, such as Arf1 and Arf6, indeed
      have been shown to each employ multiple different ArfGAPs for their regulation
      and function. We have found that two ArfGAPs, namely AMAP1 and AMAP2, exhibit a
      novel biochemical property of directly and selectively binding to GTP-Arf6
      without immediate GAPing activity, while they were previously shown to exhibit
      efficient catalytic GAPing activities to Arf isoforms except Arf6 in vitro. Such
      property of AMAPs appears to be important for AMAPs-mediated recruitment of
      auxiliary molecules, including paxillin, cortactin, amphiphysin, and intersectin,
      to sites of Arf6 activation. AMAPs thus appear to act as "effectors" rather than
      simple GAPs in some aspects of Arf6 function. This article presents methods and
      protocols developed for the functional characterization of AMAPs in Arf6
      function. These methods may be applied to other types of ArfGAPs to further
      clarify the cellular functions of ArfGAPs as well as Arfs.

PMID- 16413273
TI  - Functional assay of EFA6A, a guanine nucleotide exchange factor for ADP
      ribosylation factor 6 (ARF6), in dendritic formation of hippocampal neurons.
AB  - EFA6A is a guanine nucleotide exchange factor (GEF) that can activate ADP
      ribosylation factor 6 (ARF6) in vitro, with prominent expression in the forebrain
      including the hippocampal formation. In this section, we describe the neuronal
      transfection method and show that the overexpression of a catalytically inactive
      mutant of EFA6A induces a prominent dendritic formation of the primary
      hippocampal neurons, suggesting the intimate involvement of EFA6A in the
      regulation of neuronal dendritic development. This reliable and consistent
      neuronal transfection method will also be applicable for the vector-based RNA
      interference method.

PMID- 16413274
TI  - Functional assay of ARNO and ARF6 in neurite elongation and branching.
AB  - During development of the nervous system, neurite outgrowth is necessary for the
      formation of connections between nerve cells. Neurons are highly polarized cells
      that send out distinct processes, axons, and dendrites; however, the molecular
      regulation of the differential growth of these processes remains incompletely
      understood. Primary cultures of rat hippocampal neurons have been used to study
      many aspects of neuronal cell biology, including neurite extension, establishment
      of polarity, biogenesis of synapses, and membrane trafficking. After attachment
      to the substrate, hippocampal neurons begin sending out multiple processes by
      approximately 12 h after plating. The axonal process is derived from one of these
      processes, and is evident after 48 h in culture. Complete polarity of axons and
      dendrites is established after 7 days in culture. The establishment of these
      cultures and the ability to transfect them with potential regulatory genes allows
      the researcher to dissect out the pathways relevant to neurite extension. To
      study the role of small GTPases in neurite extension and branching, we describe
      methods for culture of hippocampal neurons, for transfection of these cells, and
      assessment of neurite extension and branching.

PMID- 16413275
TI  - Analysis of the interaction between cytohesin 2 and IPCEF1.
AB  - IPCEF1 has been reported to interact with ADP-ribosylation factor GTP exchange
      factors of the cytohesin family and function by modulating the cytohesin 2
      activity. This article describes methods used to study the interaction and
      activation of cytohesin GEFs by IPCEF1. The experimental approaches described
      here include physical and functional interaction assays by which the association
      of IPCEF1 with cytohesin 2 is explored both in vitro and in vivo. The methods
      used to analyze the physical association include GST-pull down and
      coimmunoprecipitation approaches. We also used yeast two-hybrid and
      colocalization assays to study the interaction between IPCEF1 and cytohesins. The
      functional relationship between IPCEF1 and cytohesin 2 was assessed by studying
      the effect of IPCEF1 on the in vitro and in vivo stimulation of ADP-ribosylation
      factor 6 GTP formation by cytohesin 2.

PMID- 16413276
TI  - Assay and properties of the GIT1/p95-APP1 ARFGAP.
AB  - GIT1/p95-APP1 is an adaptor protein with an aminoterminal ARFGAP domain involved
      in the regulation of ARF6 function. GIT1/p95-APP1 forms stable complexes with a
      number of proteins including downstream effectors and exchanging factors for
      members of the Rho family of small GTPases. This protein can also interact with
      other adaptor proteins implicated in the regulation of cell adhesion and synapse
      formation. The stability of the endogenous and reconstituted complexes after cell
      lysis allows the biochemical identification and characterization of the GIT1
      complexes that can be isolated from different cell types. This article presents
      methods for the identification of the endogenous and reconstituted GIT1 complexes
      that can be utilized for the biochemical and functional characterization of the
      complexes from different tissue and cell types.

PMID- 16413277
TI  - Preparation and characterization of recombinant golgin tethers.
AB  - Golgin tethers are integral or peripheral Golgi proteins with predicted coiled
      coil domains and many are known to interact directly with small GTPases of the
      Ypt/Rab or Arl families. Here we describe the preparation of recombinant golgins:
      GM130, p115 (and truncations thereof), the N-terminal fragment of giantin, CASP,
      and golgin-84.

PMID- 16413278
TI  - Purification and functional properties of the membrane fissioning protein
      CtBP3/BARS.
AB  - The fissioning protein CtBP3/BARS is a member of the CtBP transcription
      corepressor family of proteins. The characterization of this fissioning activity
      of CtBP3/BARS in both isolated Golgi membranes and in intact cells has indicated
      that the CtBP family includes multifunctional proteins that can act both in the
      nucleus and in the cytoplasm. The fissiogenic activity of CtBP3/BARS has a role
      in the fragmentation of the Golgi complex during mitosis and during intracellular
      membrane transport. This was demonstrated using a number of approaches and
      reagents, which are discussed in the following text, and which include
      recombinant proteins and mutants, antibodies, protein overexpression, RNA
      interference, antisense oligonucleotides, cell permeabilization, and electron
      miscroscopy, together with biochemical assays such as that for ADP-ribosylation.

PMID- 16413279
TI  - In vitro assays of Arf1 interaction with GGA proteins.
AB  - ADP-ribosylation factor 1 (Arf1) is a GTP-binding protein that regulates membrane
      traffic. This function of Arf1 is, at least in part, mediated by Arf1 x GTP
      binding to coat proteins such as coatomer, clathrin adaptor protein (AP)
      complexes 1 and 3, and gamma-adaptin homology-Golgi associated Arf-binding (GGA)
      proteins. Binding to Arf1 x GTP recruits these coat proteins to membranes,
      leading to the formation of transport vesicles. Whereas coatomer and the AP
      complexes are hetero-oligomers, GGAs are single polypeptide chains. Therefore,
      working with recombinant GGAs is straightforward compared to the other Arf1
      effectors. Consequently, the GGAs have been used as a model for studying Arf1
      interactions with effectors and as reagents to determine Arf1 x GTP levels in
      cells. In this chapter, we describe in vitro assays for analysis of GGA
      interaction with Arf1 x GTP and for determining intracellular Arf1 x GTP levels.

PMID- 16413280
TI  - The role of EFA6, exchange factor for Arf6, for tight junction assembly,
      functions, and interaction with the actin cytoskeleton.
AB  - In polarized epithelial cells, the tight junction has been ascribed several
      functions including the regulation of the paracellular permeability, an
      impediment to the diffusion of molecules between the apical and basolateral
      domains, a site of delivery of transport vesicles for basolateral proteins, and a
      scaffold for structural and signaling molecules. The tight junction is anchored
      physically into the apical actin cytoskeleton circumscribing the cell, which is
      known as the perijunctional actomyosin ring. This connection was first suggested
      by experiments using the actin depolymerizing drug cytochalasin, which was also
      found to disrupt the transepithelial permeability. Since then a large number of
      studies have reported the effects of drugs, molecular tools, or physiological and
      pathological conditions that alter coordinately actin organization and the tight
      junction. In support of this model, proteins of the tight junction, such as the
      members of the ZO family and occludin, have been shown to bind to actin. However,
      very little is known regarding the molecular mechanisms by which the actin
      cytoskeleton modulates tight junction functions. We have studied the role of the
      Exchange Factor for Arf6, EFA6, in tight junction assembly. By combining a large
      panel of methods, including morphological, physiological, and biochemical,
      described in detail hereafter we demonstrated that EFA6 plays a role in the
      physical association of the tight junction to the perijunctional actomyosin ring.

PMID- 16413281
TI  - In vitro reconstitution of ARF-regulated cytoskeletal dynamics on Golgi
      membranes.
AB  - Function of the secretory pathway is intimately connected to the cytoskeleton.
      Cytoskeletal dynamics and molecular motors are involved in organelle morphology
      and positioning, as well as the formation and translocation of trafficking
      intermediates such as vesicles. At least three classes of small GTPases, the ADP
      ribosylation factor (ARF), Rho, and Rab families, have been implicated in
      regulating cytoskeletal dynamics and molecular motor function within the
      secretory pathway. We have used the reconstitution of transport vesicle formation
      on isolated Golgi membranes to characterize mechanisms of ARF1 regulated actin
      polymerization. ARF1 affects cytoskeletal function in part by recruiting a
      complex between the vesicle-coat protein, coatomer, and the Rho-related GTPase,
      Cdc42, to the Golgi apparatus. Cdc42 can activate actin polymerization on Golgi
      membranes through an Arp2/3-dependent mechanism. Coatomer-bound Cdc42 plays a
      further role in regulating vesicle motility via the motor protein, dynein. Future
      studies elucidating the molecular mechanisms connecting vesicular transport with
      actin dynamics will provide important clues to the overall contribution of the
      cytoskeleton and molecular motors to protein transport. This article describes
      methods and reagents for characterizing cytoskeletal regulation at the Golgi
      apparatus through the cell-free reconstitution of vesicle formation.

PMID- 16413282
TI  - Assays and properties of arfaptin 2 binding to Rac1 and ADP-ribosylation factors
      (Arfs).
AB  - Arfaptin 1 and 2 were identified as targets for GTP bound ADP-ribosylation
      factors (Arfs). Arfaptin 1 had no significant effects on guanine nucleotide
      binding to Arfs, nor enzymatic activities of guanine nucleotide exchange factor
      (GEF) and GTPase activating protein (GAP) acting on Arfs. However, arfaptin 1
      inhibited Arf activation of cholera toxin and phospholipase D (PLD) in a dose
      dependent manner. Only GTP-bound forms of Arf1, 5, and 6 interacted with arfaptin
      1 and 2, but GTP-Arf1 showed the strongest binding to the arfaptins. In contrast
      to the binding of Arfs to arfaptins, GDP-Rac1 or dominant negative Rac1-N17N
      bound to arfaptin 2, whereas GTP-Rac1 or dominant active Rac1-Q61L did not bind
      to arfaptin 2. Neither GTP-Rac1 nor GDP-Rac1 bound to arfaptin 1. Based on our
      observation, we propose that arfaptin 2 is a target for GDP-Rac1 and for GTP
      Arf1, and is involved in interactions between the Rac1 and Arfs signaling
      pathways. This chapter describes methods for investigating the interactions of
      arfaptins 1 and 2 with GTP- or GDP-liganded Arfs and Rac1.

PMID- 16413283
TI  - Analysis of Arf interaction with GGAs in vitro and in vivo.
AB  - Small GTPases of the ADP-ribosylation factor (Arf) family regulate membrane
      traffic and dynamics in eukaryotic cells. GGAs (Golgi-localizing, gamma-adaptin
      ear homology domain, Arf-binding proteins) are a family of monomeric clathrin
      adaptor proteins that were originally identified as proteins interacting with
      Arfs and found to associate mainly with membranes of the trans-Golgi network
      (TGN). Like other adaptor and coat proteins, membrane association of GGAs is
      regulated by Arfs in a GTP-dependent manner. Together with or independent of the
      adaptor protein complex AP-1, GGAs mediate sorting of transmembrane proteins,
      including mannose 6-phosphate receptors, between the TGN and endosomes by
      clathrin-coated vesicles. This chapter describes methods to examine the
      interaction between Arfs and GGAs and to analyze the cellular function of GGAs
      regulated by Arfs.

PMID- 16413284
TI  - Arf6 modulates the beta-actin specific capping protein, betacap73.
AB  - Recent work from our laboratory has revealed that isoactin cytoskeletal and
      membrane dynamics are coordinately regulated. In this chapter, we review some of
      the recent and relevant scientific literature focusing on key aspects of
      cytoskeletal and membrane-mediated signal transduction. Additionally, we
      highlight some of the strategic molecular, biochemical, and cell-based
      methodologies that we have either developed or implemented in our efforts aimed
      at revealing the pivotal role(s) that the actin isoforms play in controlling cell
      shape and motility during developmental and/or disease-associated events.
      Furthermore, we address the central position of beta-actin and its barbed end
      specific capping protein, betacap73, in modulating nonmuscle cell membrane
      dynamics and cell migration. In studying the molecular mechanisms mediating these
      cytoskeletal protein interactions, we have recently recognized that cell motility
      and beta-actin dynamics are controlled by the direct association of betacap73
      with the plasma membrane- and endosome-associated protein, ADP-ribosylation
      factor 6 (Arf6).

PMID- 16413285
TI  - Functional assay of effectors of ADP ribosylation factor 6 during clathrin/AP-2
      coat recruitment to membranes.
AB  - Arf proteins play pivotal roles in membrane traffic, cell signaling, and actin
      cytoskeletal rearrangements. We describe here methods to functionally analyze
      interacting partner proteins of recombinantly produced N-myristoylated Arf6.
      Combined evidence from affinity purification and chemical crosslinking
      experiments, in vitro recruitment assays, and the analysis of lipid kinase
      activities indicates that Arf6-GTP facilitates clathrin/AP-2 recruitment to
      synaptic membranes by direct binding and activation of the brain-specific
      phosphatidylinositol 4-phosphate 5-kinase type Igamma (PIPK Igamma). These
      methods shall help to mechanistically dissect the role of Arf6 in regulating exo
      endocytic vesicle cycling at synapses and in related membrane trafficking events.

PMID- 16413286
TI  - Assays to study phospholipase D regulation by inositol phospholipids and ADP
      ribosylation factor 6.
AB  - Phospholipase D (PLD) is an enzyme implicated in the regulation of both exocytic
      and endocytic vesicle trafficking as well as many other processes. Consistent
      with this, the small GTPase Arf6 and regulated changes in inositol phospholipids
      levels are two factors that regulate both PLD and vesicle trafficking. Here we
      describe three methodologies through which the activation of PLD by Arf6 and
      inositol phospholipids may be investigated. The first method described is an in
      vitro protocol that allows the analysis of purified proteins or cell lysates.
      Furthermore, this protocol can be used to analyze the effects of different
      inositol phospholipids by changing the composition of the substrate vesicle. The
      major advantage of this protocol lies in the ability to analyze the effects of
      direct interactions on PLD activation by using pure proteins and lipids. The
      other two methods are in vivo protocols for the analysis of PLD activation in
      response to extracellular stimuli. Modification of cellular composition using
      overexpression/deletion or knockout of specific genes can be utilized with these
      protocols to characterize PLD activation pathways. The first of these methods
      uses the detection of radiolabeled PLD products and can be used for most cell
      types whereas the second of these two protocols is used to measure PLD products
      when radiolabeling of cells is not possible, such as freshly isolated cells that
      will not survive long enough to attain radiochemical equilibrium.

PMID- 16413287
TI  - Assay and functional properties of the tyrosine kinase Pyk2 in regulation of Arf1
      through ASAP1 phosphorylation.
AB  - The Arf-GTPase-activating protein (GAP) ASAP1 has been identified in a yeast-two
      hybrid screen as a prominent binder of the proline-rich tyrosine kinase 2 (Pyk2)
      via SH3 domain-mediated interaction. Following binding, Pyk2 directly
      phosphorylates ASAP1 on tyrosine residues 308 and 782 in vitro and in cells. To
      understand the functional impact of this interaction and subsequent
      phosphorylation, nonphosphorylated and Pyk2-phosphorylated ASAP1 have been
      generated. This material can be used for lipid-protein overlay assays and
      fluorimetric Arf-GTPase tests to show that the Pyk2-mediated tyrosine
      phosphorylation of ASAP1 modulates its GAP activity towards Arf1 in vitro. These
      studies provide the first evidence for a regulation of ASAP1 and hence Arf1
      activity by tyrosine phosphorylation and suggest a functional link between
      tyrosine kinases and Arf GTPases. Furthermore, an assay to study cellular Arf
      activation and thus GAP as well as guanine nucleotide exchange factor (GEF)
      activities and their regulation is described.

PMID- 16413288
TI  - ADP-ribosylation factor 6 regulation of phosphatidylinositol-4,5-bisphosphate
      synthesis, endocytosis, and exocytosis.
AB  - Unlike other members of the ADP-ribosylation factor (ARF) family, Arf6 is
      localized to the plasma membrane and endosomes, and regulates membrane traffic
      from and into the plasma membrane. Arf6 regulates a clathrin-independent
      endocytic membrane recycling pathway in nonpolarized cells and clathrin-dependent
      endocytosis in polarized cells. It also regulates recycling endosome traffic back
      to the plasma membrane as well as dense-core vesicle exocytosis in neuroendocrine
      cells. A key effector for Arf6 is phosphatidylinositol 4-monophosphate 5-kinase,
      which catalyzes plasma membrane synthesis of phosphatidylinositol-4,5
      bisphosphate (PIP2), a common required cofactor for several endocytic and
      exocytic membrane trafficking pathways. Long-term expression of a constitutively
      active Arf6 mutant in cells can lead to the depletion of PIP2 from the plasma
      membrane, its accumulation in intracellular vacuoles, and the inhibition of PIP2
      dependent membrane trafficking at the plasma membrane.

PMID- 16413289
TI  - Interaction of Arl1 GTPase with the GRIP domain of Golgin-245 as assessed by GST
      (glutathione-S-transferase) pull-down experiments.
AB  - Arl1 is a member of the Arf/Arl family of Ras-like GTPase superfamily. Arl1 is
      enriched in the trans-Golgi network (TGN). We have recently shown that Arl1
      regulates TGN recruitment of GRIP domain-containing Golgin-97 and Golgin-245 by
      interacting with the conserved GRIP domain present in their carboxyl (C)-termini.
      We describe here methods for the analysis of the interaction between Arl1(GTP)
      and the GRIP domain of Golgin-245 using in vitro GST pull-down experiments. GST
      Arl1(GTP) can recover endogenous Golgin-245 from HeLa cell cytosol. Furthermore,
      GST-GRIP domain of Golgin-245 can efficiently retain endogenous active Arl1. A
      pull-down assay is developed to quantify the relative level of active Arl1.

PMID- 16413290
TI  - Functional analysis of Arl1 and golgin-97 in endosome-to-TGN transport using
      recombinant Shiga toxin B fragment.
AB  - A direct transport route from early/recycling endosome (EE/RE) to the trans-Golgi
      network (TGN) is exploited by Shiga toxin (Mallard et al., 1998) and TGN38 (Ghosh
      et al., 1998). To facilitate the study of this pathway, both in vivo and in vitro
      transport assays using recombinant Shiga toxin B fragments (STxB) as protein
      cargos have facilitated the analysis of this transport event (Johannes et al.,
      1997; Mallard et al., 1998, 2002; Tai et al., 2004). We describe here the
      application of these assays to study the role of a small GTPase Arl1 and its
      effector golgin-97 in this transport process.

PMID- 16413291
TI  - Assays used in the analysis of Arl2 and its binding partners.
AB  - Arl2 is a approximately 20 kDa GTPase in the ADP-ribosylation factor (Arf) family
      within the Ras superfamily with roles in microtubule dynamics that impact the
      cytoskeleton, cell division, and cytokinesis. Arl2 has been implicated as a
      regulator of the pathway responsible for formation of properly folded tubulin
      heterodimers and in adenine nucleotide transport in mitochondria. The
      identification and characterization of Arl2 binding partners and regulators of
      Arl2 activities are critical steps in the further dissection of these and likely
      other Arl2-dependent functions. This chapter describes methods for preparing
      recombinant Arl2, loading different radiolabeled guanine nucleotides onto the
      GTPase, identifying high-affinity Arl2 binding proteins, and assaying Arl2 GTPase
      activating proteins (GAPs). These methods may also prove useful for studies of
      other Arls or other GTPases.

PMID- 16413292
TI  - Assay and functional analysis of the ARL3 effector RP2 involved in X-linked
      retinitis pigmentosa.
AB  - Mutations in RP2 cause X-linked retinitis pigmentosa and also macular and
      peripapillary atrophy. RP2 is a functional homologue of the tubulin folding
      cofactor, cofactor C, as it can replace the beta tubulin GTPase stimulating
      activity of cofactor C in an in vitro assay. An important difference between RP2
      and cofactor C is their subcellular localization. RP2 is targeted to the
      cytoplasmic face of the plasma membrane by dual N-terminal acylation, and this
      post-translational modification is important for protein function. The activity
      of tubulin folding cofactors is modulated by certain ADP ribosylation factor-like
      (Arl) proteins. It has been shown that RP2 can interact directly with Arl3. Here
      we describe the methodologies that we have developed to analyze the interaction
      of RP2 with Arl3 and to investigate the effect of RP2 post-translational
      modifications on its subcellular and tissue localization.

PMID- 16413293
TI  - Reconstitution of transport to recycling endosomes in vitro.
AB  - Using an in vitro assay instead of an approach in vivo greatly facilitates the
      analysis of complex intracellular mechanisms. This becomes particularly important
      for studying vesicular trafficking in both the endocytic and exocytic pathways
      with multiple transport routes connecting cellular organelles. Our chapter
      describes a novel cell-free assay that reconstitutes endosomal transport to
      recycling endosomes. The method measures transport of transferrin, a marker for
      endocytosis/recycling, from an endosome-enriched donor fraction to immunoisolated
      Rab11-positive acceptor recycling endosomes. Transfer of acridinium-labeled
      transferrin is detected by a highly sensitive chemiluminescence reaction using a
      luminometer.

PMID- 16413294
TI  - Robust colorimetric assays for dynamin's basal and stimulated GTPase activities.
AB  - Dynamin, unlike many GTPase superfamily members, exhibits a relatively rapid
      basal rate of GTP hydrolysis that is not rate-limited by GTP binding or GDP
      dissociation. Also unique to dynamin GTPase family members is their ability to
      self-assemble into rings and helical stacks of rings either in solution or onto
      lipid templates. Self-assembly stimulates dynamin's GTPase activity by >100-fold.
      Given these robust rates of GTP hydrolysis compared to most GTPases, GTP
      hydrolysis by dynamin can be easily measured using a simple colorimetic assay to
      detect released phosphate. We describe this assay and report variations in assay
      conditions that have contributed to the wide range of reported values for
      dynamin's basal and assembly-stimulated rates of GTP hydrolysis.

PMID- 16413295
TI  - Clathrin-coated vesicle formation from isolated plasma membranes.
AB  - Endocytic clathrin-coated vesicle (CCV) formation is a complex process involving
      a large number of proteins and lipids. The minimum machinery and the hierarchy of
      the events involved in CCV formation have yet to be defined. Here we describe an
      in vitro assay for CCV formation from highly purified rat liver plasma membranes.
      This rapid and easy assay can be used to quantitatively evaluate the different
      protein requirements for different endocytic receptors.

PMID- 16413296
TI  - Nucleotide binding and self-stimulated GTPase activity of human guanylate-binding
      protein 1 (hGBP1).
AB  - The synthesis of human guanylate-binding protein 1 (hGBP1) is induced by
      interferon-gamma and its biological function is related to antiviral activity and
      regulation of proliferation. It interacts with guanine nucleotides, and its
      catalytic activity on GTP hydrolysis leads to the formation of phosphate ions and
      both GDP and GMP. Similar to other large GTPases like dynamin, hGBP1 shows higher
      specific GTP hydrolysis activity with increasing concentration of the protein.
      This is based on nucleotide-dependent self-association of hGBP1, which leads to
      self-stimulation of its GTPase activity. In this chapter we describe the
      characterization of the basic biochemical properties of hGBP1. Essentially, the
      biological activity of a GTPase is controlled by the type of nucleotide bound.
      Therefore, nucleotide binding is quantified in terms of affinity and dynamics
      since both of these aspects are important for the occurrence of hGBP1 bound to
      the one or the other nucleotide. In addition, we analyze the self-stimulated
      GTPase activity and show how to extract the hGBP1 homodimer dissociation constant
      from these data. Finally, with the help of size exclusion chromatography,
      nucleotide-dependent formation of hGBP1 dimers and tetramers is demonstrated.
      These biochemical characteristics may help to further understand the biological
      function of hGBP1.

PMID- 16413297
TI  - Stimulation of dynamin GTPase activity by amphiphysin.
AB  - Dynamin functions in the fission of endocytic pits in the process of clathrin
      mediated endocytosis. Dynamin GTPase activity is essential for its fission
      activity, and it is stimulated by self-assembly as well as by interacting with
      its binding partners, such as microtubules, SH3 domain containing proteins, or
      inositol phospholipids. Amphiphysin 1, SH3 domain-containing binding partner of
      dynamin 1, is proposed to cooperatively function in endocytosis. Amphiphysin 1 is
      essential for dynamin-dependent synaptic vesicle recycling in the synapse, and it
      enhances dynamin-dependent vesicle formation in vitro. In order to elucidate the
      molecular mechanism underlying the amphiphysin's effect, we measured dynamin
      GTPase activity in the presence of both amphiphysin 1 and lipid membranes. We
      describe here in detail the procedure of the dynamin GTPase assay and the results
      demonstrating stimulatory effect of amphiphysin on dynamin GTPase activity, which
      is highly dependent on the liposome size.

PMID- 16413298
TI  - Tuba, a GEF for CDC42, links dynamin to actin regulatory proteins.
AB  - Tuba is a 178kD protein containing four NH2-terminal SH3 domains, a central Dbl
      homology (DH) domain followed by a BAR domain, and two COOH-terminal SH3 domains.
      The four NH2-terminal SH3 domains bind the GTPase dynamin, a protein critical for
      the fission of endocytic vesicles. The DH domain functions as a CDC42-specific
      guanine nucleotide exchange factor and is unique among DH domains because it is
      followed by a BAR domain rather than a PH domain. The COOH-terminal SH3 domain
      binds directly to N-WASP and Ena/VASP proteins, key regulatory proteins of the
      actin cytoskeleton, and recruits a larger protein complex comprising additional
      actin regulatory factors. The properties of Tuba provide new evidence for a
      functional link between dynamin, endocytosis, and actin. The presence of a BAR
      domain, rather than a PH domain, may reflect its action at high curvature regions
      of the plasma membrane. Its multiple binding sites for dynamin generate an
      exceptionally high avidity for this GTPase and make the NH2-terminal region of
      Tuba a very useful tool for the one-step purification of dynamin.

PMID- 16413300
TI  - Rapid purification of native dynamin I and colorimetric GTPase assay.
AB  - Dynamin I is a large GTPase enzyme required in membrane constriction and fission
      during multiple forms of endocytosis. The first method described here is for the
      rapid purification of native dynamin from peripheral membrane extracts of sheep
      brain using ammonium sulfate precipitation and affinity purification on
      recombinant SH3 domains. The method greatly enriches for dynamin I at high purity
      and allows for large-scale biochemical and functional studies. The second method
      is a nonradioactive, high-throughput colorimetric GTPase assay for dynamin
      activity. The approach is based on terminating incubations with EDTA and the use
      of malachite green for high-sensitivity detection of inorganic phosphate release.
      The two methods will facilitate high-throughput screens for potential dynamin
      inhibitors or activators.

PMID- 16413299
TI  - Expression and properties of sorting nexin 9 in dynamin-mediated endocytosis.
AB  - Sorting nexin 9 (SNX9) is identified as an important regulator of dynamin
      function in clathrin-mediated endocytosis. SNX9 recruits dynamin to the plasma
      membrane and promotes its GTPase activity, resulting in membrane constriction and
      ultimate transport vesicle scission. This chapter describes procedures to express
      recombinant SNX9, to biochemically characterize the cytosolic complex between
      SNX9 and dynamin, and to identify additional interacting partners of SNX9. Assays
      are presented to investigate the requirements for SNX9-dependent membrane
      recruitment of dynamin in vitro and in vivo.

PMID- 16413301
TI  - Assays and functional properties of auxilin-dynamin interactions.
AB  - The large GTPase dynamin is required for budding of clathrin-coated vesicles from
      the plasma membrane, but its mechanism of action is still not understood. Growing
      evidence indicates that the GTP-bound form of dynamin recruits downstream
      partners that execute the fission reaction. Recently, we reported nucleotide
      dependent interactions between dynamin and auxilin, which suggested that auxilin
      cooperates with dynamin during vesicle formation. Here we describe three
      different in vitro assays that monitor auxilin-dynamin interactions, as well as
      fluorescence lifetime imaging microscopy that identify direct interactions
      between dynamin and auxilin in cells.

PMID- 16413302
TI  - Assay and functional analysis of dynamin-like protein 1 in peroxisome division.
AB  - Recent studies have demonstrated that peroxisome division requires at least one
      dynamin-like protein, Vps1p, in the yeast Saccharomyces cerevisiae and DLP1
      (DRP1) in mammalian cells. Although the requirement for these proteins in
      peroxisome division is supported by many lines of evidence, their roles in
      peroxisome division have yet to be identified. Given the independence of
      peroxisomes from other organelle systems, the peroxisome system appears to have
      unique attributes for studying the function of dynamin-like proteins in organelle
      division. Here, we present methods that have been used for studying the role of
      DLP1 in peroxisome biogenesis and division.

PMID- 16413303
TI  - In vitro reconstitution of discrete stages of dynamin-dependent endocytosis.
AB  - Many proteins involved in vesicle budding are able to interact with lipids and to
      deform membranes. In this review we present three in vitro assays that can be
      used to study the roles of these types of proteins and to reconstitute distinct
      stages of vesicle budding and tubule formation. In the first assay, the dynamic
      effect of peripheral membrane proteins on liposome morphology is studied,
      providing insight into the roles of proteins (e.g., the endocytic proteins;
      dynamins, epsins, amphiphysins, and endophilins) in deforming membranes and in
      recognizing membrane curvature. In the second assay, preformed lipid nanotubes
      are used to mimic the neck of a coated vesicle. These nanotubes form a suitable
      template to study molecules of the dynamin family, allowing visualization of the
      different conformations of dynamin that occur during vesicle scission. Finally,
      lipid monolayers have been used as mimics of the internal leaflet of the plasma
      membrane to investigate early stages of clathrin-coated pit formation. In
      principle this can equally be used to study budding mechanisms of other coated
      vesicle types. A combination of these three assays has given considerable insight
      into the roles of endocytic proteins and is allowing reconstitution and
      dissection of the different stages of vesicle formation.

PMID- 16413304
TI  - A continuous, regenerative coupled GTPase assay for dynamin-related proteins.
AB  - Dynamin-related proteins (DRPs) compose a diverse family of proteins that
      function, through GTPase stimulated self-assembly, to remodel cellular membranes.
      The molecular mechanism by which DRPs mediate membrane remodeling events and the
      specific role of their GTPase cycle is still not fully understood. Although DRPs
      are members of the GTPase superfamily, they possess unique kinetic properties. In
      particular, they have relatively low affinity for guanine nucleotides and, under
      conditions that favor self-assembly, they have high rates of GTP turnover.
      Established fixed time point assays used for the analysis of assembly stimulated
      GTPase activity are prone to inaccuracies due to substrate depletion and are also
      limited by lack of time resolution. We describe a simple, continuous, coupled GTP
      regenerating assay that tackles the limitations of the fixed time point assays
      and can be used for the kinetic analysis of DRP GTP hydrolysis under unassembled
      and assembled conditions.

PMID- 16413305
TI  - Assay and properties of the mitochondrial dynamin related protein Opa1.
AB  - Opa1, also known as Mgm1 in yeast, is a mitochondrial member of the dynamin
      family. Unlike other dynamin family members, Opa1 has an N-terminal mitochondrial
      targeting sequence, suggesting that this protein is imported into mitochondria.
      Here, we describe biochemical techniques, such as mitochondrial isolation,
      digitonin extraction, a protease protection assay, and carbonate extraction, that
      were used to determine that mammalian Opa1 resides in the intermembrane space
      where it is tightly bound to the inner membrane. In addition, we describe
      bacterial expression of the Opa1 GTPase domain, methods for purification, and an
      in vitro assay for GTP hydrolysis.

PMID- 16413306
TI  - Assay and functional analysis of dynamin-like Mx proteins.
AB  - Mx proteins are interferon-induced large guanosine triphosphatases (GTPases) that
      share structural and functional properties with dynamin and dynamin-like
      proteins, such as self-assembly and association with intracellular membranes. A
      unique property of some Mx proteins is their antiviral activity against a range
      of RNA viruses, including influenza viruses and members of the bunyavirus family.
      These viruses are inhibited at an early stage in their life cycle, soon after
      host cell entry and before genome amplification. The association of the human MxA
      GTPase with membranes of the endoplasmic reticulum seems to support its antiviral
      function by providing an interaction platform that facilitates viral target
      recognition, MxA oligomerization, and missorting of the resulting multiprotein
      complex into large intracellular aggregates.

PMID- 16413308
TI  - Molecular weight determination of peptides and proteins by ESI and MALDI.
AB  - Several topics are covered, namely, general aspects important for mass
      determination of peptides and proteins, sample preparation for both ESI and
      MALDI, and various mass analyzers coupled to these ionization techniques.
      Finally, the discussion is carried out on peptide and protein mass analysis as
      related to accuracy and precision of mass determination for both ESI-MS and MALDI
      MS.

PMID- 16413309
TI  - Batch introduction techniques.
AB  - Mass spectrometry (MS) is widely used as a rapid tool for peptide profiling and
      protein identification. However, the success of the method is compromised by
      dirty and contaminated samples. Moreover, analysis from a small sample volume
      with a relative high concentration is usually required. In this chapter,
      different microscale sample preparation methods are discussed for off-line,
      matrix-assisted laser desorption/ionization (MALDI) and nanoelectrospray
      ionization (nanoESI) MS analysis.

PMID- 16413310
TI  - In-solution digestion of proteins for mass spectrometry.
AB  - Mass spectrometry (MS) has gradually replaced classical methods as a major tool
      in protein sequencing and characterization. However, the sample preparation
      repertoire has not changed very much; it has just been adjusted to the needs of
      the new analytical method. In this chapter frequently used in-solution enzymatic
      digestions and chemical cleavages are reviewed. In addition, some practical
      recommendations as well as the advantages and shortcomings of the methods are
      discussed.

PMID- 16413311
TI  - Identification of phosphorylation sites using microimmobilized metal affinity
      chromatography.
AB  - One of the most important roles that mass spectrometry (MS) has played in the
      late twentieth and early twenty-first centuries has been to assist in the growth
      of knowledge of dynamic phosphorylation events. Not only has MS allowed
      researches to pinpoint the site of phosphorylation, but it has also enabled them
      to identify the kinase/phosphatase pairs responsible for regulation of a specific
      modification as well as to follow the functional consequences of the observed
      phosphorylation events on the biology of the system. For phosphorylation
      analysis, the important contribution of MS has been critical but not definitive.
      There are numerous methods that have been applied with success, yet none are
      generally applicable to all analyses. So, for the time being, researchers in the
      field must select from a panel of methods to find (de)phosphorylation events. In
      the work described in this chapter, a collection of integrated methods are
      presented. A detailed account is provided for phosphorylation capture via on- and
      off-line immobilized metal affinity chromatography (IMAC). This is followed by a
      suite of useful strategies for discovery of phosphorylation positioning through
      sequence determination by phosphate-specific diagnostic ion scans, including
      precursor and product ion scans, neutral loss scans, and in-source dissociation
      and post-source decay.

PMID- 16413312
TI  - Mapping posttranslational modifications of proteins by MS-based selective
      detection: application to phosphoproteomics.
AB  - This chapter outlines general principals that apply to the analysis of
      posttranslational modifications of proteins, with an emphasis on phosphoproteins.
      Mass spectrometry (MS)-based approaches for selective detection and site-specific
      analysis of posttranslationally modified peptides are described, and an MS-based
      method that relies on production and detection of fragment ions specific for the
      modification(s) of interest and that was developed in the authors' laboratory is
      described in detail. The method is applicable to selective detection of N- and O
      linked carbohydrates in glycoproteins, O-linked sulfate, and N- and O-linked
      lipids. Detailed procedures for application of this strategy to phosphorylation
      site mapping are presented here.

PMID- 16413313
TI  - Characterization of protein N-glycosylation.
AB  - Although mass spectrometry (MS)-based protein identification is a straightforward
      task, the characterization of most posttranslational modifications still
      represents a challenge. N-glycosylation with its well known consensus sequence,
      common core structure, and "universally" active endoglycosidase seems to belong
      to the easier category. In this chapter, MS methods for the analysis of N
      glycosylated proteins are reviewed. In particular, LC-MS analysis of glycoprotein
      digests is discussed in detail. The examples included in this chapter illustrate
      the improved detection sensitivities achieved during the last decade. The
      characterization of site heterogeneity and of site occupancy is addressed. Low
      energy collision-induced dissociation (CID) fragmentation of N-linked
      glycopeptides and their sodium-adducts is also described.

PMID- 16413315
TI  - Analysis of glycosylphosphatidylinositol protein anchors: the prion protein.
AB  - Membrane proteins constitute a substantial fraction of the human proteome. A
      small subgroup associates with membranes through the presence of a C-terminal
      lipid anchor that is joined to the protein via a phosphoglycan. The prion protein
      (PrP), an abnormally folded form that causes fatal neurodegeneration, is one
      example of a glycosylphosphatidylinositol (GPI)-anchored protein. Although GPI
      anchored proteins were first recognized some 20 years ago (in the mid-1980s),
      relatively few GPI anchors have been analyzed in detail. Therefore, a description
      of the analysis of the PrP-GPI anchor using a variety of mass spectrometric
      methods is of interest even though some of the approaches adopted could be
      facilitated through the use of newer, more sensitive techniques.

PMID- 16413314
TI  - Methods in enzymology: O-glycosylation of proteins.
AB  - Cell surface and extracellular proteins are O-glycosylated, where the most
      abundant type of O-glycosylation in proteins is the GalNAc attachment to serine
      (Ser) or threonine (Thr) in the protein chain by an a-glycosidic linkage. Most
      eukaryotic nuclear and cytoplasmic proteins modified by a-linked O-GlcNAc to Ser
      or Thr exhibit reciprocal O-GlcNAc glycosylation and phosphorylation during the
      cell cycle, cell stimulation, and/or cell growth. Less-investigated types of O
      glycosylation are O-fucosylation, O-mannosylation, and O-glucosylation, but they
      are functionally of high relevance for early stages of development and for vital
      physiological functions of proteins. Glycosaminoglycans are a-linked to
      proteoglycans via a xylose-containing tetrasaccharide, represented by linear
      chains of repetitive disaccharides modified by carboxylates and O- or/and N
      linked sulfates. Analysis of O-glycosylation by mass spectrometry (MS) is a
      complex task due to the high structural diversity of glycan and protein factors.
      The parameters in structural analysis of O-glycans include determination of (i) O
      glycosylation attachment sites in the protein sequence, (ii) the type of attached
      monosaccharide moiety, (iii) a core type in the case of GalNAc O-glycosylation,
      (iv) the type and size of the oligosaccharide portion, (v) carbohydrate branching
      patterns, (vi) the site of monosaccharide glycosidic linkages, (vii) the
      anomericity of glycosidic linkages, and (viii) covalent modifications of the
      sugar backbone chains by carbohydrate- and noncarbohydrate-type of substitutents.
      Classical and novel analytical strategies for identification and sequencing of O
      glycans by MS are described. These include methods to analyze O-glycans after
      total or partial release from the parent protein by chemical or enzymatic
      approach or to analyze O-glycosylated peptides by mapping and sequencing from
      proteolytic mixtures. A recombination process of multiply charged glycopeptides
      with electrons by electron capture dissociation Fourier transform ion cyclotrone
      resonance (FTICR)-MS has been introduced and is instrumental for nonergodic
      polypeptide backbone cleavages without losses of labile glycan substituents. A
      method for O-glycoscreening under increased sensitivity and efficient sequencing
      as a combination of an on-line coupling of capillary electrophoresis separation,
      as well as an automated MS-tandem MS (MS/MS) switching under variable energy
      conditions collision-induced dissociation (CID) protocol, is beneficial for
      determination of O-acetylation and oversulfation (Bindila et al., 2004a; Zamfir
      et al., 2004a). O-glycomics by robotized chip-electrospray/ionization (ESI)-MS
      and MS/MS on the quadrupole time-of-flight (QTOF) and FTICR analyzers, accurate
      mass determination, and software for assignment of fragmentation spectra
      represent essentials for high-throughput (HTP) in serial screenings (Bindila et
      al., 2004b; Froesch et al., 2004; Vakhrushev et al., 2005). Dimerization of
      intact O-glycosylated proteins can be investigated by matrix-assisted laser
      desorption/ionization-time-of-flight (MALDI-TOF)-MS after blotting.

PMID- 16413316
TI  - Comprehensive mass spectrometric analysis of the 20S proteasome complex.
AB  - The 20S proteasome is a multicatalytic protein complex that plays an important
      role in intracellular protein degradation from archaebacteria to eukaryotes. This
      complex is made up of two copies each of seven different alpha (alpha) and seven
      different beta (beta) subunits arranged into four stacked rings
      (alpha7beta7beta7alpha7). Although the proteasome's cylindrical structure is
      conserved, the subunit composition of the 20S protein complex varies during the
      evolution, and the number of subunits increases from archaebacteria to mammals.
      To fully characterize the 20S proteasome subunit composition and understand the
      subunit functions, we, the authors of this chapter, have developed and employed
      various mass spectrometry (MS)-based approaches to generate a comprehensive
      profile of the 20S proteasomes from rat liver and Tropanosoma brucei. We have
      identified 7 alpha and 10 beta subunits, including 7 essential and 3 nonessential
      beta subunits from rat 20S proteasome complex using two-dimensional (2-D) gel
      electrophoresis and tandem MS (MS/MS). In addition, multiple isoforms of most of
      the subunits were determined; indicating the composition of rat 20S proteasome
      complex was much more complicated than expected. Further analysis of the intact
      protein molecular weight of each subunit using LC-MS confirmed the heterogeneous
      population of the 20S proteasome and revealed that many of the experimental
      measured molecular weights do not correspond well with the theoretical values
      deduced from the sequences in protein databases. This finding is mostly due to
      the sequence errors in the protein databases and possible posttranslational
      modifications. Although the protein sequences of rat 20S proteasome are present
      in the databases, the sequences of the 20S proteasome from T. brucei were not
      available at the time when the analysis was carried out. To determine the subunit
      composition of the 20S proteasome from T. brucei, we developed a homology-based
      database searching tool to identify unknown proteins based on the novel sequences
      determined by de novo sequencing using MS/MS. As a result, 14 subunits (7 alpha
      and 7 beta) were identified on the 2-D gel, which was later confirmed by the full
      length sequences. Using the same approach, we also identified and characterized
      an activator protein, PA26, from T. brucei. The purified recombinant PA26 self
      assembles into a heptamer ring, which can bind and activate the 20S proteasome
      from T. brucei as well as rat. Compared to the human PA28 complex, PA26 may be
      the prototype activator protein involved in proteasomal protein degradation.
      Therefore, the MS-based strategy developed here for identification of the known
      and unknown protein complexes can be generalized for the study of other protein
      complexes.

PMID- 16413317
TI  - The analysis of multiprotein complexes: the yeast and the human spliceosome as
      case studies.
AB  - The yeast and human spliceosomes represent the first two multiprotein complexes
      of which protein components were identified solely by mass spectrometry (MS). In
      this chapter, the different approaches used for the purification of these protein
      complexes, the MS analysis of the components, and some functional
      characterization strategies adopted are discussed. Even though from the time of
      analysis up to 2005 much has been achieved in terms of purification techniques,
      MS protein analysis and sequence information in public databases, the key
      knowledge gained from the very early complex analyses still hold true today. The
      analysis of protein complexes is a powerful approach for understanding the
      organization of proteins and how they act in units to exert their biological
      effects. The analysis also creates hypotheses for the role of novel proteins in
      the context of the cellular function of the protein complex under study. However,
      the work on the spliceosomes described in this chapter also illustrates the
      relative ease of protein identification by MS and the difficulty to provide
      detailed functional information for the vast amount of data generated in such a
      study.

PMID- 16413318
TI  - The use of mass spectrometry to identify antigens from proteasome processing.
AB  - Mass spectrometry (MS) is a powerful tool for the characterization of antigenic
      peptides that play a major role in the immune system. Most of the major
      histocompatibility complex (MHC) class I peptides are generated during the
      degradation of intracellular proteins by the proteasome, a catalytic complex
      present in all eukaryotic cells. This chapter focuses on the contribution of MS
      to the understanding of the mechanisms of antigen processing by the proteasome.
      This knowledge may be valuable for the design of specific inhibitors of
      proteasome, which has recently been recognized as a therapeutic target in cancer
      therapies and for the development of efficient peptidic vaccines in
      immunotherapies. Examples from the literature have been chosen to illustrate how
      MS data can contribute first to the understanding of the mechanisms of
      proteasomal processing and, second, to the understanding of the crucial role of
      proteasome in cytotoxic T lymphocytes (CTL) activation. The general strategy
      based on MS analyses used in these studies is also described.

PMID- 16413319
TI  - Glycosphingolipid structural analysis and glycosphingolipidomics.
AB  - Sphingosines, or sphingoids, are a family of naturally occurring long-chain
      hydrocarbon derivatives sharing a common 1,3-dihydroxy-2-amino-backbone motif.
      The majority of sphingolipids, as their derivatives are collectively known, can
      be found in cell membranes in the form of amphiphilic conjugates, each composed
      of a polar head group attached to an N-acylated sphingoid, or ceramide.
      Glycosphingolipids (GSLs), which are the glycosides of either ceramide or myo
      inositol-(1-O)-phosphoryl-(O-1)-ceramide, are a structurally and functionally
      diverse sphingolipid subclass; GSLs are ubiquitously distributed among all
      eukaryotic species and are found in some bacteria. Since GSLs are secondary
      metabolites, direct and comprehensive analysis (metabolomics) must be considered
      an essential complement to genomic and proteomic approaches for establishing the
      structural repertoire within an organism and deducing its possible functional
      roles. The glycosphingolipidome clearly comprises an important and extensive
      subset of both the glycome and the lipidome, but the complexities of GSL
      structure, biosynthesis, and function form the outlines of a considerable
      analytical problem, especially since their structural diversity confers by
      extension an enormous variability with respect to physicochemical properties.
      This chapter covers selected developments and applications of techniques in mass
      spectrometric (MS) that have contributed to GSL structural analysis and
      glycosphingolipidomics since 1990. Sections are included on basic characteristics
      of ionization and fragmentation of permethylated GSLs and of lithium-adducted
      nonderivatized GSLs under positive-ion electrospray ionization mass spectrometry
      (ESI-MS) and collision-induced mass spectrometry (CID-MS) conditions; on the
      analysis of sulfatides, mainly using negative-ion techniques; and on selected
      applications of ESI-MS and matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) to emerging GSL structural, functional, and analytical
      issues. The latter section includes a particular focus on evolving techniques for
      analysis of gangliosides, GSLs containing sialic acid, as well as on
      characterizations of GSLs from selected nonmammalian eukaryotes, such as
      dipterans, nematodes, cestodes, and fungi. Additional sections focus on the issue
      of whether it is better to leave GSLs intact or remove the ceramide; on
      development and uses of thin-layer chromatography (TLC) blotting and TLC-MS
      techniques; and on emerging issues of high-throughput analysis, including the use
      of flow injection, liquid chromatography mass spectrometry (LC-MS), and capillary
      electrophoresis mass spectrometry (CE-MS).

PMID- 16413320
TI  - Mapping bacterial glycolipid complexity using capillary electrophoresis and
      electrospray mass spectrometry.
AB  - This chapter presents the application of capillary electrophoresis coupled to
      electrospray mass spectrometry (CE-ES-MS) for the analysis of complex bacterial
      lipopolysaccharides (LPS) from pathogenic strains of Haemophilus influenzae and
      Neisseria meningitidis. A discussion is included of the development of
      electrophoretic conditions conducive to trace-level enrichment and separation of
      closely related glycoforms and isoforms, which provided sensitive detection of
      glycolipids from as little as five bacterial colonies. The chapter also describes
      the use of mixed MS scanning functions to aid the identification of specific
      functionalities and immunodeterminants of LPS, such as pyrophosphoethanolamine,
      phosphocholine, and N-acetyl neuraminic acid (Neu5Ac), which represent less than
      2% of the overall LPS population. The combination of high-resolution capillary
      electrophoresis with sensitive tandem mass spectrometry (MS/MS) provides a unique
      analytical tool to probe the subtle structural changes resulting from
      oligosaccharide branching and location of substituted LPS isoforms. The ability
      to detect a diverse LPS population over a wide dynamic range of expression using
      CE-MS enables the correlation of structural changes between bacterial strains and
      isogenic mutants to assign functional gene relationship.

PMID- 16413322
TI  - What an andrologist/urologist should know about free radicals and why.

PMID- 16413323
TI  - Current and future pharmacotherapeutic strategies in treatment of premature
      ejaculation.

PMID- 16413324
TI  - Intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy.
AB  - OBJECTIVES: To present a modification of our previously published technique of
      nerve-sparing endoscopic extraperitoneal radical prostatectomy (nsEERPE).
      METHODS: The technique enables puboprostatic ligament preservation, leaving
      intact the puboprostatic ligaments, endopelvic fascia, periprostatic fascia, and
      neurovascular bundles (intrafascial dissection). The modification of nsEERPE was
      performed in 50 consecutive patients. RESULTS: The total operative time was 131
      minutes (range 75 to 165). The mean catheterization time was 5.4 days (range 5 to
      14). CONCLUSIONS: The intrafascial nsEERPE is a modification of our previously
      published standard nsEERPE. The anterior approach to the periprostatic fascia
      enables less traumatic dissection from the prostate and thus, theoretically, a
      more viable neurovascular bundle.

PMID- 16413326
TI  - Clinical implication of routine stone culture in percutaneous nephrolithotomy--a
      prospective study.
AB  - OBJECTIVES: To evaluate the correlation between preoperative urine culture (UC)
      and intraoperative stone culture (SC) and the impact of SC findings on clinical
      decisions. METHODS: UC and intraoperative fragmented SC were prospectively
      obtained in all patients undergoing percutaneous nephrolithotomy between January
      2004 and March 2005. Patients with a positive UC received a full course of
      antibiotics before surgery. All postoperative systemic inflammatory response
      syndrome (SIRS) events were recorded, as was the antibiotic regimen used and any
      changes in antibiotic treatment secondary to the SC results. RESULTS: The study
      group consisted of 75 consecutive patients. Of these 75 patients, 33 (49%) had
      sterile UC and SC results. Both urine and renal stones were colonized in 17
      patients (24%); in 6 of them, the UC and SC showed different pathogens. A
      colonized SC associated with a sterile UC was found in 19 patients (25%). The
      calculated UC sensitivity, specificity, and positive and negative predictive
      value for the detection of stone colonization was 30%, 94%, and 84% and 58%,
      respectively. Seventeen patients (22%) had postoperative SIRS. In 13 of them, a
      change in antibiotic treatment was made according to the SC findings. On
      univariate analysis, the incidence of SIRS was not related to the length of the
      operation, stone-free rate, or supracostal or infracostal access. The relative
      risk of SIRS when the SC was positive was 3.6. CONCLUSIONS: Renal calculi
      pathogens are one of the predisposing factors for infectious events; however,
      preoperative UC often fails to grow stone-colonizing bacteria. Intraoperative SC
      may be essential in directing the antibiotic regimen postoperatively and should
      be routinely used.

PMID- 16413325
TI  - Diabetes and benign prostatic hyperplasia progression in Olmsted County,
      Minnesota.
AB  - OBJECTIVES: To examine the association of diabetes and progression of benign
      prostatic hyperplasia in a prospective population-based sample of residents of
      Olmsted County, Minnesota, with serial surrogate measures of benign prostatic
      hyperplasia. METHODS: A cohort of 2115 white men aged 40 to 79 years was randomly
      selected from an enumeration of the 1990 Olmsted County, Minnesota population
      (55% participation rate). Participants completed a previously validated baseline
      questionnaire that assessed lower urinary tract symptom severity from questions
      similar to the American Urological Association Symptom Index. The questionnaire
      also asked whether they had ever been diagnosed by a physician as having
      diabetes. Participants also voided into a portable urometer to measure the peak
      urinary flow rate. A 25% random subsample underwent transrectal ultrasonography
      to determine the prostate volume, and the prostate-specific antigen level was
      determined. Dynamic follow-up was performed biennially for 12 years with the
      measures repeated at each visit. RESULTS: Of the 2115 men 111 had diabetes at
      baseline. The men with diabetes had a significantly greater median annual
      percentage change in the American Urological Association Symptom Index (0.40
      versus 0.15, P = 0.04) and a trend toward a greater median annual percentage of
      change in the peak urinary flow rate (-4.7% versus -2.9%, P = 0.06) compared with
      those without diabetes. However, no significant difference was found in the
      annual percentage of change in the prostate volume or serum prostate-specific
      antigen level. CONCLUSIONS: The results of this study suggest that the presence
      of diabetes may be more closely associated with the dynamic components of lower
      urinary tract function than with benign prostatic hyperplasia progression, per
      se.

PMID- 16413327
TI  - Nephrostomy tube-free percutaneous nephrolithotomy for patients with large stones
      and staghorn stones.
AB  - OBJECTIVES: To perform a retrospective study to assess the outcome and safety of
      64 nephrostomy tube-free percutaneous nephrolithotomies (PCNLs) in 62 patients
      with calculi 3 cm or greater. METHODS: Between March 2001 and June 2004, 365
      consecutive patients underwent 389 PCNLs at our hospital. Electrocauterization of
      the access tract was performed at the end of the operation in every patient. No
      nephrostomy tube was inserted in the patient if a bloodless tract had been
      obtained. Of the 389 PCNLs, 154 were performed in patients with a stone size of 3
      cm or greater. Of these 154 PCNLs, 64 were performed with the nephrostomy tube
      free modification (group 1) and 90 were performed with insertion of the
      nephrostomy tube after the operation (group 2). The hospital course and
      complications were evaluated in both groups. RESULTS: No statistically
      significant differences in age, stone size, urinary tract infection rate, or
      blood transfusion rate were found between those with and without insertion of the
      nephrostomy tube. Fourteen patients in group 1 had complete staghorn stones. A
      shorter operative time, lower analgesic requirement, and shorter postoperative
      hospital stay were noted in the group with the nephrostomy tube-free modification
      (group 1). CONCLUSIONS: With adequate homeostasis, nephrostomy tube-free PCNL can
      be performed in patients with complicated urolithiasis without any increase in
      morbidity.

PMID- 16413329
TI  - Irrigation and drainage properties of three-way urethral catheters.
AB  - OBJECTIVES: To evaluate in an in vitro study the irrigation and drainage
      capabilities of a variety of available catheters. Three-way Foley catheters are
      used when irrigation of the bladder is anticipated to prevent or manage blood
      clots in the bladder. METHODS: Six operators applied maximal one-handed pressure
      irrigation with a catheter-tip syringe through the irrigation and drainage ports
      of the Bardex and Dover three-way catheters (16F to 26F). Maximal manual
      irrigation flow was recorded using a flowmeter. Continuous gravity irrigation and
      drainage flows were measured by suspending a 2-L irrigation bag 80 cm above the
      catheters and fastening an artificial bladder to the drainage tip of each Foley
      catheter with the catheter balloon inflated to 30 mL. RESULTS: The Bardex 22F and
      24F catheters had superior manual irrigation using the irrigation port (maximal
      urinary flow rate 8.9 +/- 1.3 mL/s and 9.5 +/- 1.5 mL/s, respectively, P <
      0.000001) compared with the Dover 22F and 24F catheters. The Bardex and Dover 22F
      catheters (maximal urinary flow rate 29.0 +/- 1.9 mL/s and 29.3 +/- 1.9 mL/s,
      respectively, P = 0.66) and 24F catheters (maximal urinary flow rate 30.5 +/- 2.0
      mL/s and 30.6 +/- 1.2 mL/s, respectively, P = 0.83) performed equally in manual
      irrigation using the drainage port. The Bardex 22F (average flow rate 1.6 +/- 0.1
      mL/s, P < 0.00001) and 24F (average flow rate 1.7 +/- 0.0 mL/s, P < 0.000001)
      catheters exhibited better continuous irrigation and flow than the Dover 22F and
      24F catheters. CONCLUSIONS: Three-way catheters are placed in situations in which
      efficient bladder irrigation is essential for patient safety. The Bardex 22F to
      26F catheters optimized continuous bladder irrigation of the catheters tested.

PMID- 16413328
TI  - Is there a role for alpha1-blockers in treating double-J stent-related symptoms?
AB  - OBJECTIVES: To evaluate the effect of alfuzosin in improving symptoms in, and
      quality of life of, patients with indwelling double-J ureteral stents. METHODS: A
      total of 100 patients, 50 men and 50 women (mean age 54.2 years), with unilateral
      ureteral stone-related hydronephrosis, who had opted for conservative management
      with insertion of a double-J ureteral stent, were prospectively randomized into
      two groups. Group 1 included 50 patients who received 10 mg of alfuzosin, once
      daily for 4 weeks, and group 2 consisted of 50 patients who received placebo for
      the same period. All patients completed a validated Ureteral Stent Symptom
      Questionnaire (USSQ) 4 weeks after stent placement. RESULTS: The mean urinary
      symptom index score was 21.6 in group 1 and 28.1 in group 2 (P < 0.001). Stent
      related pain was reported by 44% of patients in group 1 and 66% of patients in
      group 2 (P = 0.027). The mean pain index score was 14.6 in group 1 and 17.4 in
      group 2 (P = 0.047). The mean general health index score was statistically
      greater (P < 0.001) in group 1 compared with in group 2 (8 versus 11.4,
      respectively). Among sexually active patients, the mean sexual score was 2.3 in
      group 1 and 2.9 in group 2 (P = 0.017). CONCLUSIONS: Stent-related symptoms were
      present in 66% of the controls (group 2). Alfuzosin improved a subset of stent
      related urinary symptoms and pain. Patients receiving alfuzosin had their sexual
      function and general health better preserved.

PMID- 16413330
TI  - Outcomes of hand-assisted laparoscopic nephrectomy in technically challenging
      cases.
AB  - OBJECTIVES: To evaluate the outcomes of hand-assisted laparoscopic nephrectomy in
      patients with significant complicating clinical factors. METHODS: We performed a
      retrospective review of 322 hand-assisted laparoscopic nephrectomy cases that
      were completed at a single institution from 1998 to 2004. Patients with a history
      of extensive abdominal surgery or prior procedures on the affected kidney,
      evidence of perirenal inflammation, renal lesions 10 cm or more in diameter, or
      level I renal vein thrombus were included. RESULTS: A total of 42 patients were
      included in this series. Of these, 16 patients had a lesion 10 cm or larger, 10
      had a renal vein thrombus, and 10 had undergone prior major abdominal surgery.
      Many patients had more than one complicating factor. Another 6 patients had a
      history of prior renal procedures or chronic inflammatory processes involving the
      affected kidney. One Stage T4 renal tumor with paraspinous muscle invasion was
      successfully managed without conversion. The overall mean operative time and
      estimated blood loss was 235 minutes and 439 mL, respectively, with a mean
      hospital stay of 4 days. Four patients (9.5%) required open conversion (one renal
      hilar injury, two failure to progress, and one persistent bleeding from the renal
      fossa). Postoperative complications included pulmonary embolism in 1, ileus in 1,
      and chronic obstructive pulmonary disease exacerbation in 1 patient. One patient
      developed an incarcerated port site hernia requiring reoperation. CONCLUSIONS:
      Hand-assisted laparoscopic nephrectomy is an attractive minimally invasive option
      in the setting of significant complicating factors. This technique may facilitate
      the successful laparoscopic completion of these challenging cases with reasonable
      operative times, blood loss, and complication rates.

PMID- 16413331
TI  - Comparison of laparoscopic partial nephrectomy and laparoscopic cryoablation for
      renal hilar tumors.
AB  - OBJECTIVES: To compare laparoscopic partial nephrectomy (LPN) and laparoscopic
      cryoablation (LC) for the management of small renal tumors located near the renal
      hilum. METHODS: A retrospective chart review was performed on all patients who
      underwent LPN and LC. A total of 23 patients (12 LPN and 11 LC) had tumors
      located within 5 mm of the renal hilar vasculature. Patient data were
      retrospectively analyzed for specific parameters, including operative time,
      efficacy, morbidity, and postoperative course. RESULTS: All 23 cases were
      successfully completed laparoscopically. The mean operative time for LPN and LC
      was 2.8 hours and 2.3 hours, respectively (P = 0.03). The mean estimated blood
      loss was 197 mL for LPN and 70 mL for LC (P < 0.01). The analgesic requirement
      for those undergoing LPN and LC was 29 mg morphine equivalent and 23 mg morphine
      equivalent, respectively (P = 0.41). The hospital stay for patients in the LPN
      and LC groups was 3.9 days and 3.2 days respectively (P = 0.55). No
      intraoperative complications occurred in either group. Six patients experienced
      nine complications in the LPN group. The complications included hemorrhage in 1,
      fever in 1, ileus in 1, urinary tract infection in 1, urine leak in 4, and
      transient postoperative neuropathy in 1. The LC group had no postoperative
      complications. In the LC cohort, no disease recurrence developed during the 11.3
      months of follow-up. No positive margins were found in the LPN cohort, and with a
      mean follow-up of 12 months, none have developed recurrence. CONCLUSIONS: LPN for
      hilar tumors is a reasonable surgical option but carries an increased risk of
      urine leak. LC for hilar tumors has a shorter operative time and results in
      significantly fewer postoperative complications. Long-term follow-up data for
      both techniques remain unavailable.

PMID- 16413332
TI  - Responsiveness of symptom scales for interstitial cystitis.
AB  - OBJECTIVES: To evaluate the responsiveness of composite scales to change over
      time in a clinical trial of patients with interstitial cystitis (IC). The
      measurement of symptoms in IC includes the O'Leary-Sant Symptom and Problem
      Indexes and the University of Wisconsin Interstitial Cystitis Inventory and
      scales that measure the individual symptom domains of pain/discomfort, urgency,
      and voiding frequency. METHODS: The data were derived from a randomized clinical
      trial conducted by the Interstitial Cystitis Clinical Trials Group. Participants
      met the National Institutes of Health-National Institute for Diabetes, and
      Digestive and Kidney Diseases criteria for IC and reported at least moderate pain
      and frequency. The primary endpoint was a patient-reported global response
      assessment (GRA) at 24 weeks. Secondary endpoints included the three composite
      indexes, pain/discomfort and urgency, and 24-hour frequency. Responsiveness was
      assessed by comparing symptom score changes against response categories defined
      by the GRA. RESULTS: Of the 121 subjects in the original trial, 94 with complete
      data were included. All three composite indexes were sensitive to subject
      improvement over time as measured by the GRA. A 1.2-point change in the O'Leary
      Sant indexes and a 3.1-point change in the Wisconsin IC inventory corresponded to
      a one-category change in the GRA. Individual symptoms were also responsive. The
      correlation was high among the changes in the six outcome measures. CONCLUSIONS:
      The three composite symptom scales are responsive to change over time in patients
      with IC. These indexes provide important insight into symptom changes and are
      recommended as secondary endpoints in future clinical trials of IC. Additional
      endpoints addressing individual symptom domains should also be considered to aid
      in the evaluation of effect mechanisms.

PMID- 16413333
TI  - Effects of pollen extract preparation Prostat/Poltit on lower urinary tract
      symptoms in patients with chronic nonbacterial prostatitis/chronic pelvic pain
      syndrome: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: To assess the efficacy and safety of the pollen extract preparation
      Prostat/Poltit in the treatment of patients with chronic nonbacterial
      prostatitis/chronic pelvic pain syndrome. METHODS: In a double-blind study, 60
      patients between 20 and 55 years old with chronic nonbacterial
      prostatitis/chronic pelvic pain syndrome were randomized to receive
      Prostat/Poltit or placebo for 6 months. The patients had been symptomatic for
      more than 6 months without response to any given therapy. The patients were
      evaluated at the start of the treatment and after 6 months of treatment with the
      help of a symptom questionnaire covering the symptoms in seven pain locations,
      five voiding symptoms, three storage symptoms, and four sex-related symptoms.
      RESULTS: The overall clinical evaluation of the treatment result showed that
      after treatment for 6 months more patients taking Prostat/Poltit were cured or
      improved than patients taking placebo. No adverse reactions to the treatment were
      found. CONCLUSIONS: Prostat/Poltit is superior to placebo in providing
      symptomatic relief in men with chronic nonbacterial prostatitis/chronic pelvic
      pain syndrome.

PMID- 16413334
TI  - Abdominal plain film in patients admitted with clinical suspicion of renal colic:
      should it be replaced by low-dose computed tomography?
AB  - OBJECTIVES: To evaluate a low-dose abdominal computed tomography (LDCT) protocol,
      delivering a radiation dose close to that delivered by an abdominal plain film
      (APF), in patients with a clinical suspicion of renal colic. METHODS: A total of
      139 patients for whom an APF was requested for suspicion of renal colic were
      randomized into two groups. The patients in group 1 (n = 68) underwent an
      admission LDCT scan delivering a 2.1-mSv radiation dose to women and 1.6 mSv to
      men, instead of the APF. Patients in group 2 (n = 71) underwent an APF. Clinical
      and radiologic follow-up data were obtained for each patient. The number of
      additional abdominal ultrasound and CT scans performed to reach a confident final
      diagnosis and determine the proper treatment was compared between the two groups.
      A mean effective radiation dose was obtained in each group. RESULTS: Of the 68
      patients in group 1 (LDCT), 10 (15%) underwent ultrasonography, 9 (13%)
      conventional abdominal CT, and 2 (3%) both. In group 2 (APF), the corresponding
      percentages were 27% (19 of 71), 28% (20 of 71), and 23% (16 of 71). Of the 68
      patients in group 1, 47 (69%) did not require any additional examinations
      compared with 16 (23%) of the 71 patients in group 2 (P < 0.0001). The mean
      effective dose was 3.5 and 6.9 mSv in groups 1 and 2, respectively (P < 0.0001).
      CONCLUSIONS: In patients with suspicion of renal colic, replacing the admission
      APF with our LDCT protocol will significantly reduce the need for additional CT
      or ultrasonography. Also, our LDCT protocol decreases by almost 50% the mean
      radiation dose per patient.

PMID- 16413335
TI  - Gyrus bipolar versus standard monopolar transurethral resection of the prostate:
      a randomized prospective trial.
AB  - OBJECTIVES: To compare bipolar plasmakinetic (PK) with standard monopolar
      transurethral resection of the prostate (TURP). METHODS: A total of 70 patients
      were prospectively randomized into two groups: 35 patients underwent PK TURP with
      the Gyrus device, and 35 patients underwent standard monopolar TURP. We evaluated
      the time to catheter removal and hospital discharge, operating time, blood loss,
      postoperative irrigation, complications, urinary flow rates, symptom relief, and
      postvoid residual volumes. RESULTS: At baseline, the study groups were comparable
      in age, prostate volume, mean prostate-specific antigen value, International
      Prostate Symptom Score, quality-of-life score, flow rate, and postvoid residual
      volume. The mean catheterization time was 72 and 100 hours in the PK and standard
      groups, respectively. This difference was statistically significant (P <0.05), as
      was the difference in the time to hospital discharge. No difference was found in
      the mean resection time, amount of resected tissue, or variations in hemoglobin
      and sodium levels. The improvement in flow rate, postvoid residual volume,
      International Prostate Symptom Score, and quality-of-life score was comparable
      between the two groups at 12 months of follow-up. CONCLUSIONS: In our experience,
      PK TURP showed comparable perioperative results to those obtained with standard
      TURP, but with more favorable postoperative outcomes. The resection time and
      blood loss were similar between the two groups, but the need for continuous
      bladder irrigation after surgery and time to catheter removal and hospital
      discharge were significantly shorter in the PK group.

PMID- 16413336
TI  - Food groups and risk of benign prostatic hyperplasia.
AB  - OBJECTIVES: To evaluate the role of a wide range of foods on the risk of benign
      prostatic hyperplasia (BPH), we conducted a case-control study in Italy between
      1991 and 2002. Although BPH is an extremely common condition, particularly among
      older men, its risk factors, including dietary ones, remain largely undefined.
      METHODS: Included in the study were 1369 patients younger than 75 years old
      surgically treated for BPH and 1451 controls younger than 75 years of age who had
      been admitted to the same hospitals as cases for a wide spectrum of acute, non
      neoplastic conditions. A validated and reproducible food frequency questionnaire,
      including 78 foods and beverages, plus a separate section on alcoholic beverages,
      was used to assess patients' dietary habits 2 years before diagnosis or hospital
      admission. Multivariate odds ratios (OR) were obtained after allowance for energy
      intake and other major potential confounding factors. RESULTS: A significant
      trend of increasing risk with more frequent consumption was found for cereals (OR
      1.55 for the greatest versus lowest quintile), bread (OR 1.69), eggs (OR 1.43),
      and poultry (OR 1.39). Inverse associations were observed for soups (OR 0.74),
      pulses (OR 0.74), cooked vegetables (OR 0.66), and citrus fruit (OR 0.82). No
      association was observed for milk and yogurt products, coffee and tea, pasta and
      rice, fish, cheese, row vegetables, potatoes, fruit, or desserts. CONCLUSIONS:
      The results of this study suggest a role for dietary habits on the risk of BPH.
      In particular, a diet rich in cereals and some types of meat and poor in
      vegetables and pulses may have an unfavorable effect in this Italian population.

PMID- 16413337
TI  - Use of expired breath ethanol measurements in evaluation of irrigant absorption
      during high-power potassium titanyl phosphate laser vaporization of prostate.
AB  - OBJECTIVES: To evaluate formally the risk and levels of irrigant absorption
      during high-power potassium titanyl phosphate (KTP) laser vaporization of the
      prostate by the Greenlight PV system using the expired breath ethanol technique.
      METHODS: Forty consecutive patients underwent laser vaporization of the prostate.
      Of these patients, 17 had a preoperative transrectal ultrasound estimation of the
      prostate volume (mean 97 cm3). All procedures were performed under general
      anesthesia, by either of two consultants or a trainee. A 1% ethanol solution was
      used as irrigation fluid. Throughout the operation, the expired breath was
      analyzed for ethanol using a standard alcometer "plumbed" into the anesthetic
      circuit. Venous blood samples were taken immediately before and after the
      procedure for measurements of serum sodium and plasma alcohol levels. RESULTS: On
      average, 155,000 J of laser energy was delivered in 47 minutes. In all patients
      and on all occasions, the expired breath ethanol remained at 0. No statistically
      significant change was found in the serum sodium concentration during the
      procedure (P = 0.42), and no patient displayed any clinical evidence of
      transurethral resection syndrome. CONCLUSIONS: The results of this study have
      confirmed, for the first time, the lack of significant absorption of irrigation
      fluid during high-power KTP vaporization of the prostate using a recognized
      sensitive technique and the safety of using sterile water as that irrigant. This
      was the case even in those patients with very large prostates who are usually
      considered at high risk of experiencing the clinical consequences of fluid
      absorption during transurethral resection of the prostate and regardless of the
      experience of the surgeon.

PMID- 16413338
TI  - Development of nomogram to predict acute urinary retention or surgical
      intervention, with or without dutasteride therapy, in men with benign prostatic
      hyperplasia.
AB  - OBJECTIVES: To develop a prediction model, or nomogram, that would predict the
      probability that a man with benign prostatic hyperplasia would experience acute
      urinary retention (AUR) or require surgical intervention (SI) within 2 years,
      with or without dutasteride therapy. METHODS: We modeled 4294 men treated in the
      Phase III dutasteride benign prostatic hyperplasia trials. These men were
      characterized at baseline by a number of parameters, including the American
      Urological Association Symptom Index, Benign Prostatic Hyperplasia Impact Index
      questionnaire, prior use of selective alpha1-blockers, prostate volume, prostate
      specific antigen level, and maximal flow rate. Cox proportional hazards
      regression analysis was used to relate these baseline variables to their future
      probability of AUR/SI within 2 years. The nomogram was internally validated with
      bootstrapping to assess its discrimination and calibration. Discrimination was
      quantified as the concordance index. RESULTS: The nomogram appeared to be
      accurately calibrated and discriminating (concordance index 0.71, P <0.001).
      CONCLUSIONS: We constructed a nomogram for predicting the probability that a man
      would experience AUR or require SI within 2 years of benign prostatic hyperplasia
      diagnosis. At 24 months of follow-up, 7.4% of placebo patients and 3.7% of
      dutasteride patients had experienced AUR and/or SI, representing a 50% relative
      risk reduction and a 3.7% absolute risk reduction. For the greatest risk patient
      randomized to the Phase III dutasteride trial, the nomogram predicted a maximal
      risk of 27%, significantly greater than the median risk of the placebo-treated
      patients.

PMID- 16413339
TI  - Novel technique for management of distal ureter and en block resection of bladder
      cuff during hand-assisted laparoscopic nephroureterectomy.
AB  - OBJECTIVES: To report our experience with a novel flexible cystoscopic approach
      to excise the en block bladder cuff and juxtavesical ureter during hand-assisted
      laparoscopic nephroureterectomy. The optimal technique for excising the distal
      ureter and bladder cuff during nephroureterectomy continues to evolve. METHODS:
      Hand-assisted laparoscopic nephroureterectomy was performed in 6 patients. A hand
      assist device and two 5 to 12-mm ports were placed in the mid and upper abdomen.
      Two 10-mm clips were placed on the proximal ureter to occlude it, and the kidney
      was resected in the usual fashion. An additional 5 to 12-mm port was placed in
      the midline between the umbilicus and symphysis pubis. The ureter was dissected
      down into the pelvis to the level of the bladder. Without repositioning the
      patient, a flexible cystoscope was inserted into the bladder and a 2-cm bladder
      cuff excised using a 5F electrode on cutting current, with coagulating current
      used as needed. The specimen was removed intact through the hand port. RESULTS:
      The mean time to resect the distal bladder cuff was 30 minutes (range 22 to 35).
      The mean estimated blood loss was 254 mL. The mean operating room time was 264
      minutes, mean hospital stay 6.3 days, and mean time to a general diet 2.6 days.
      All patients underwent cystography at 7 to 10 days postoperatively, with no
      extravasation or diverticula. Cystoscopic and computed tomography follow-up
      demonstrated no evidence of recurrence. CONCLUSIONS: This technique allows for
      complete resection of the kidney, distal ureter, and a cuff of bladder, avoiding
      repositioning.

PMID- 16413340
TI  - Simplified Indiana pouch with multiple teniamyotomies.
AB  - OBJECTIVES: To describe a retrospective review of a single-institution, single
      surgeon (M.G.) experience with 44 simplified Indiana pouch with multiple
      teniamyotomies without detubularization and reconfiguration. METHODS: From April
      1999 to May 2003, 44 patients underwent radical cystectomy and continent urinary
      diversion with a simplified Indiana pouch technique using teniamyotomies without
      detubularization and reconfiguration. The tenia was sectioned across the whole
      width and deepened as far as the submucosal layer, with 2 to 3 cm between each
      teniamyotomy. The efferent tract of the reservoir was prepared using the
      appendix. If it was unsuitable, an ileum invagination nipple fixed in the
      ileocecal valve was constructed. RESULTS: The mean follow-up was 3 years (range 1
      to 5). Continence was excellent for 40 patients (91%); in 4 patients (9%),
      daytime incontinence was reported. The urodynamic studies showed an average
      pressure at 350 mL of capacity of 19.6 cm H2O (range 15.1 to 25.5). The average
      pressure at maximal capacity (400 to 600 mL) was 32.3 cm H2O (range 28.5 to 35).
      Long-term complications occurred in 15 patients (34%), with a mean onset of 13.4
      months postoperatively. CONCLUSIONS: Our experience showed that a modified
      Indiana pouch with multiple teniamyotomies has a good capacity with low internal
      pressure and good continence. Thus, even with the comparable results of other
      continent pouch models, our modified Indiana pouch is a valid alternative because
      of its simplicity to perform.

PMID- 16413341
TI  - Safety of carbon bead injection for incontinence in patients taking warfarin.
AB  - OBJECTIVES: To determine the safety of the use of Durasphere in patients
      receiving warfarin anticoagulation. METHODS: This case series included patients
      requiring long-term anticoagulation who also had intrinsic sphincteric deficiency
      or mixed urinary incontinence, and bladder outlets without hypermobility. All
      patients, with the exception of the 1 man in the study, were treated under local
      anesthesia with periurethral carbon bead injections, while receiving therapeutic
      doses of warfarin. RESULTS: Between 1999 and 2004, 20 such patients received
      carbon bead injections, on 36 different occasions, during therapeutic warfarin
      administration. Two complications related to the anticoagulation were
      encountered, one minor complication of a small periurethral hematoma and the
      other more severe, with a patient developing urinary retention and intravesical
      hemorrhage. CONCLUSIONS: In most cases, the injection of carbon beads under local
      anesthesia in patients receiving therapeutic warfarin anticoagulation can be
      safely performed without reversal of the anticoagulation.

PMID- 16413342
TI  - Association between marijuana use and transitional cell carcinoma.
AB  - OBJECTIVES: Marijuana smoking has been implicated as a causative factor in
      traditionally tobacco-related tumors of the head and neck and of the lung. When
      associated with marijuana use, such tumors occur in a much younger patient
      population than do similar tumors in tobacco smokers. Owing to the large number
      of young men with a history of marijuana presenting with transitional cell
      carcinoma to VA facilities, this study was designed to compare the marijuana use
      among young (aged less than 60 years) transitional cell carcinoma patients with
      that among age-matched controls. METHODS: Fifty-two men aged less than 60 years
      presenting consecutively with transitional cell carcinoma and 104 age-matched
      controls (defined by having no history of transitional cell carcinoma, hematuria,
      or irritative voiding symptoms, as well as unremarkable results on urinalysis and
      urine cytology) completed questionnaires about exposure to various potential
      carcinogens, including radiation, Agent Orange, smoked or processed meats, dyes,
      tobacco, and marijuana. RESULTS: Of the 52 transitional cell carcinoma patients,
      46 (88.5%) reported a history of habitual marijuana usage, and 72 (69.2%) of the
      age-matched controls gave a history of habitual marijuana use. This difference
      was statistically significant (P = 0.008). In those with transitional cell
      carcinoma, marijuana use significantly correlated with tumor stage, grade, and
      number of recurrences. CONCLUSIONS: Marijuana smoking might increase the risk of
      transitional cell carcinoma.

PMID- 16413343
TI  - Value of clusterin immunoreactivity as a predictive factor in muscle-invasive
      urothelial bladder carcinoma.
AB  - OBJECTIVES: To determine whether clusterin immunoreactivity of muscle-invasive
      bladder carcinoma can predict disease-related survival of patients treated by
      radical cystectomy. METHODS: Multi-tissue arrays were constructed from 132 tumors
      and stained immunohistochemically using a mouse monoclonal antibody (clone 7D1).
      Positive clusterin staining was defined as immunoreactivity in more than 10% of
      tumor cells. We also studied tumor proliferation (Ki-67 antigen), p53, and Her2
      expression. Immunoreactivity was compared with disease-related survival.
      Univariate and multivariate analyses were performed. RESULTS: Positive
      immunohistochemical clusterin expression was found in 25% of the tumors. On
      univariate analysis, clusterin immunoreactivity (P = 0.048), tumor stage (P =
      0.011), nodal status (P = 0.0001), sex (P = 0.039), Ki-67 antigen index (P =
      0.011), and Her2 expression (P = 0.020) were significantly associated with
      disease-related survival. On multivariate analysis, tumor stage (P = 0.01), nodal
      status (P = 0.0001), Ki-67 antigen (P = 0.0001), and Her2 expression (P = 0.001)
      were identified as significant independent predictive factors; clusterin
      expression missed the level of statistical significance by only a narrow margin
      (P = 0.058). CONCLUSIONS: Although clusterin immunoreactivity showed only a trend
      towards an independent prognostic relevance in this study, we conclude that it
      may be used, in addition to conventional and other immunohistochemical
      prognosticators, as a supplementary tool to provide more prognostic information
      in patients undergoing cystectomy for muscle-invasive bladder cancer.

PMID- 16413344
TI  - Evaluation of concordance of Gleason score between prostatectomy and biopsies
      that show more than two different Gleason scores in positive cores.
AB  - OBJECTIVES: To evaluate variables that may predict the Gleason score of radical
      prostatectomy specimens in patients with more than two different Gleason scores
      in the positive cores of their biopsy specimens. METHODS: We reviewed the
      pathologic data of 98 patients who had more than two different Gleason scores in
      12-site biopsy specimens. We assessed the following biopsy parameters: the
      greatest Gleason score on the biopsy specimen, the Gleason score of the greatest
      tumor percentage in the core, the Gleason score of the largest linear cancer
      length, and the greatest tumor ratio score (Gleason score of the greatest total
      tumor length of the same Gleason score/total core length of the same Gleason
      score). We also assessed the concordance in Gleason scores between biopsy
      specimens and prostatectomy specimens. RESULTS: The greatest tumor ratio score
      was associated with the greatest (67%) concordance rate. The concordance of the
      greatest Gleason score on biopsy specimens was only 49%. When stratified into
      categories of well-differentiated (Gleason score 6 or less), moderate (Gleason
      score 7), and poorly differentiated (Gleason score 8 or more), the grade
      concordance rate of the greatest tumor ratio score was 73%. The grade concordance
      rate of the Gleason scores of the greatest tumor percentage in the core, Gleason
      score core with maximal tumor length, and the greatest Gleason score was 64%,
      62%, and 57%, respectively. CONCLUSIONS: If biopsy specimen results in more than
      two different Gleason scores in the positive cores, the greatest tumor ratio
      score may be the most useful variable with regard to the prediction of the final
      Gleason score in the radical prostatectomy specimen.

PMID- 16413346
TI  - Differences in clinicopathologic features of prostate cancer between black and
      white patients treated in the 1990s and 2000s.
AB  - OBJECTIVES: We have previously reported on the disparity in the clinicopathologic
      features of prostate cancer between black and white patients at our equal-access
      institution during the 1990s. The goal of this study was to determine whether the
      worse clinicopathologic features of prostate cancer in black patients have
      persisted in the 2000s. METHODS: We examined 362 men (224 black and 138 white)
      treated with radical prostatectomy at the Veterans Affairs Medical Center in New
      York. We compared the clinicopathologic variables between 227 patients treated
      during the 1990s (group 1) and 135 treated in the 2000s (group 2). RESULTS: In
      group 1, black patients were significantly younger (P < 0.001) and had a greater
      prostate-specific antigen (PSA) level (P = 0.001), Gleason score (P = 0.005), and
      stage (P = 0.03) than white patients. In group 2, black patients continued to
      have significantly greater PSA levels (P = 0.04) and Gleason scores (P = 0.005)
      than white patients. Comparing only the black patients, those in group 2 had
      significantly lower PSA levels (P < 0.001) and stage (P = 0.03), but had worse
      Gleason scores (P = 0.03) than those in group 1. On multivariate analysis, black
      patients were significantly more likely to have a worse Gleason score (P = 0.005)
      than white patients. CONCLUSIONS: Our data have demonstrated a narrowing of the
      differences in pathologic stage between black and white patients in the 2000s.
      However, black men have continued to have worse Gleason scores and greater PSA
      levels than white patients. These findings suggest that there may be different
      patterns of molecular alterations in black men that may contribute to the poor
      tumor differentiation. Additional research is underway to better characterize
      these underlying molecular mechanisms.

PMID- 16413345
TI  - Relationship between primary Gleason pattern on needle biopsy and
      clinicopathologic outcomes among men with Gleason score 7 adenocarcinoma of the
      prostate.
AB  - OBJECTIVES: To examine the relationship among needle biopsy primary grade,
      prostatectomy grade, and postprostatectomy biochemical recurrence among men with
      Gleason score 7 disease. METHODS: We identified 320 men with Gleason score 7
      tumors on prostate biopsy treated with radical prostatectomy between 1991 and
      2001 by a single surgeon. None of these patients had received neoadjuvant or
      adjuvant hormonal therapy or radiotherapy. The chi-square test and Kaplan-Meier
      method were used to evaluate the correlation among biopsy Gleason score,
      prostatectomy Gleason score, and biochemical recurrence. RESULTS: A total of 252
      (79%) and 68 (21%) men had primary Gleason pattern 3 and 4 identified on needle
      biopsy, respectively. Of the patients with Gleason pattern 3 + 4 tumors on
      biopsy, 24% were upgraded to primary pattern 4 or more on final pathologic
      analysis. Of the patients with Gleason pattern 4 + 3 tumors on biopsy, 47% were
      downgraded to primary pattern 3 or less on final pathologic analysis. The
      actuarial risk of biochemical prostate-specific antigen recurrence was
      significantly lower among patients with Gleason pattern 4 + 3 on biopsy, if the
      prostatectomy Gleason score was downgraded to 3 + 4 or less (P = 0.03).
      CONCLUSIONS: Approximately 47% of men with a diagnosis of Gleason pattern 4 + 3
      on needle biopsy are downgraded at radical prostatectomy and will have
      biochemical prostate-specific antigen recurrence-free outcomes similar to
      patients originally diagnosed with Gleason pattern 3 + 4 adenocarcinoma. This
      group of patients may benefit from definitive treatment such as radical
      prostatectomy for management of their disease.

PMID- 16413347
TI  - Lifestyle and health-related quality of life of men with prostate cancer managed
      with active surveillance.
AB  - OBJECTIVES: To assess the impact of lifestyle on health-related quality of life
      (HR-QOL), perceived stress, and self-reported sexual function in men with early
      stage prostate cancer electing active surveillance. METHODS: A total of 44
      intervention and 49 usual-care control participants were enrolled in a randomized
      clinical trial examining the effects of lifestyle changes on prostate cancer
      progression. The intervention consisted of a low-fat, vegan diet, exercise, and
      stress management. Participants completed the Medical Outcomes Study Short Form
      36 Health Status Survey (a measure of mental and physical HR-QOL), the Perceived
      Stress Scale, the Sexual Function subscale of the University of California, Los
      Angeles, Prostate Cancer Index, and measures of lifestyle behaviors (to yield an
      overall lifestyle index) at baseline and 12 months. The data were analyzed using
      analysis of variance for repeated measures. The relationship between lifestyle
      and QOL was also analyzed using multiple linear regression analyses. RESULTS:
      Intervention participants had significantly improved their lifestyle compared
      with controls at 12 months. The quality-of-life scores were high across groups
      and time points. However, a healthier lifestyle was related to better QOL at
      baseline. Participants in both groups who reported a healthier lifestyle also
      reported better mental and physical HR-QOL and sexual function. Furthermore,
      participants whose lifestyle improved over time showed enhanced physical HR-QOL
      and decreased perceived stress. CONCLUSIONS: Men who choose active surveillance
      for early-stage prostate cancer are able to make comprehensive lifestyle changes.
      Although the average QOL was already high in this sample, individuals who
      improved their lifestyle enhanced their QOL further.

PMID- 16413348
TI  - Development of a nomogram to predict probability of positive initial prostate
      biopsy among Japanese patients.
AB  - OBJECTIVES: Several nomograms for prostate cancer detection have recently been
      developed. Because the incidence of prostate cancer is lower among Asian men,
      nomograms based on Western populations cannot be directly applied to Japanese
      men. We, therefore, developed a model for predicting the probability of a
      positive initial prostate biopsy using clinical and laboratory data from a
      Japanese male population. METHODS: Data were collected from 834 Japanese male
      referrals who underwent initial prostate biopsies as individual screening. We
      analyzed age, total prostate-specific antigen (PSA) level, free/total PSA (f/t
      PSA) ratio, prostate volume, and digital rectal examination findings. Of these
      data, we randomly reserved 20% for study validation. Logistic regression analysis
      estimated relative risk, 95% confidence intervals, and P values. RESULTS:
      Independent predictors of a positive biopsy result included elevated PSA levels,
      decreased f/T PSA ratio, advanced age, small prostate volume, and abnormal
      digital rectal examination findings. We developed a predictive nomogram for an
      initial positive biopsy using these variables. The area under the receiver
      operating characteristic curve for the model was 81.8%, which was significantly
      greater than that of the prediction based on PSA alone (area under the receiver
      operating characteristic curve 67.8%). If externally validated, applying this
      model could reduce unnecessary biopsy procedures by 32% and reduce the overall
      need for prostate biopsies by 26%. CONCLUSIONS: In this study of a Japanese
      population, incorporating clinical and laboratory data into a prebiopsy nomogram
      significantly improved the prediction of prostate cancer compared with
      predictions based solely on the individual factors.

PMID- 16413349
TI  - Influence of blood transfusions during radical retropubic prostatectomy on
      disease outcome.
AB  - OBJECTIVES: Blood transfusion in patients with malignant neoplasms may alter the
      disease outcome because of a theoretical immunomodulatory effect. This effect may
      reduce prostate-specific antigen (PSA)-free and disease-specific survival in
      patients with prostate cancer after radical prostatectomy. However, the results
      in published studies have been contradictory, and this effect has not yet been
      determined. METHODS: We evaluated 1412 patients after radical prostatectomy from
      1984 to 2003 in a retrospective analysis, with a special focus on the rate and
      type of blood transfusions, specifically heterologous versus autologous blood.
      Univariate analysis and Cox regression analysis were performed to evaluate the
      impact of blood transfusions on disease outcome. RESULTS: The overall transfusion
      rate was 56.7%. The rate dropped from 88.9% in 1988 to 9.1% in 2002. PSA
      recurrence (greater than 0.5 ng/mL) was noted in 11.0% in patients without and in
      26.0% with blood transfusions, which was not statistically significant on Kaplan
      Meier analysis. Again, no difference was noted when patients were stratified
      according to the type (autologous versus heterologous) or the amount (2 U or less
      versus more than 2 U) of blood transfusion. Evaluating overall survival, again no
      differences were found. The established Cox regression model also proved that
      blood transfusions had no impact on disease outcome. CONCLUSIONS: Our
      retrospective analysis did not detect any effect of blood transfusions in
      patients with prostate cancer after radical prostatectomy. If a negative adverse
      effect occurs, this effect must be minimal. However, the infectious risk and the
      costs of blood transfusions should be reason enough to reduce blood loss and the
      transfusion rate further in patients with prostate cancer.

PMID- 16413350
TI  - No immediate treatment after biochemical failure in patients with prostate cancer
      treated by external beam radiotherapy.
AB  - OBJECTIVES: The treatment of patients with asymptomatic prostate cancer with
      biochemical failure (BF) remains controversial. The early introduction of
      hormonal therapy causes important secondary effects and increases costs. Our
      general policy has been to follow-up patients with low prostate-specific antigen
      (PSA) levels and a long PSA doubling time without therapy. We report our
      experience using such an approach. METHODS: Between 1992 and 2000, 676 patients
      with localized prostate cancer were treated with radical radiotherapy, with or
      without adjuvant hormonal therapy at our institution. Asymptomatic patients with
      BF, no clinical evidence of metastatic disease, a low PSA level, and long PSA
      doubling time were considered for follow-up without immediate hormonal therapy.
      The prognostic factors such as stage and Gleason score were not considered when
      electing follow-up without additional therapy. The follow-up included at least
      two annual visits with physical examination and PSA determination. RESULTS: With
      a median follow-up of 85 months, 285 patients (42%) had BF. In 178 of these men,
      the rising PSA level was the only abnormality. Of these, 113 were followed up
      without additional therapy and 65 received hormonal therapy. Of the 113 patients
      in the untreated group, 101 (89%) were alive and asymptomatic at the last follow
      up visit and 12 (11%) had died of causes other than prostate cancer. The long
      term outcomes were similar in both groups. CONCLUSIONS: Expectant management,
      without initial hormonal therapy, may be a reasonable option for selected
      patients with prostate cancer who present with BF without metastatic disease
      after radical external beam radiotherapy. This decision is important because the
      early introduction of hormonal therapy is associated with side effects and is
      expensive.

PMID- 16413351
TI  - Intensity-modulated versus conventional pelvic radiotherapy for prostate cancer:
      analysis of acute toxicity.
AB  - OBJECTIVES: To provide a single-institution analysis of the influence of pelvic
      intensity-modulated radiotherapy (RT) on acute genitourinary (GU) and
      gastrointestinal (GI) toxicity. METHODS: The records of 610 consecutive patients
      with prostate cancer receiving RT were reviewed. Of these 610 patients, 49 had
      received a prostate boost preceded by pelvic RT (PRT), 15 intensity-modulated PRT
      (IM-PRT), and 34 four-field PRT (4F-PRT). The dosimetric endpoints for the
      bladder, rectum, and target for the PRT plans were compared using the paired t
      test; similar dosimetric analyses were done for the composite plans. Acute GU and
      GI toxicity were compared using the chi-square test. Ordered logit regression
      analyses were performed using all major treatment factors as covariates. RESULTS:
      The bladder and rectum dosimetric endpoints were improved for IM-PRT compared
      with 4F-PRT for the PRT portion of the treatment plan (P = 0.06 and P = 0.03,
      respectively) and for the composite treatment plan (P = 0.04 and P = 0.01,
      respectively), at the expense of greater target inhomogeneity in the PRT portion
      of the treatment plan (P < 0.01). GU toxicity was significantly lower in the IM
      PRT group (P < 0.001), and GI toxicity was similar in both groups (P = 0.637).
      The regression analyses showed that intensity-modulated RT for the pelvic portion
      of treatment was the only factor significantly predicting for GU toxicity (P =
      0.05); no major treatment factor reached significance in predicting GI toxicity.
      CONCLUSIONS: Compared with 4F-PRT, the use of IM-PRT improved dosimetric
      outcomes, was not associated with a reduction in acute GI toxicity, and was
      associated with a reduction in acute GU toxicity in the treatment of prostate
      cancer.

PMID- 16413352
TI  - Prevalence of osteopenia and osteoporosis by central and peripheral bone mineral
      density in men with prostate cancer during androgen-deprivation therapy.
AB  - OBJECTIVES: To determine the prevalence of osteopenia and osteoporosis by central
      (spine and hip) and peripheral (radius) bone mineral density (BMD) in men with
      prostate cancer undergoing androgen-deprivation therapy (ADT). Low BMD and
      fractures are prevalent in this group of men. Most published studies on ADT
      related bone loss have documented the loss of BMD in the spine and hip as
      measured by dual x-ray absorptiometry. In one study, the loss of BMD was most
      pronounced at the radius. METHODS: In a chart review of patients receiving ADT,
      the spine and hip BMD results were recorded in 89 patients. Of these 89 patients,
      the BMD of the radius was also recorded in 53. RESULTS: In the 89 patients with
      BMD measurements of the spine and hip, 24 (26.9%) had osteoporosis of the hip or
      spine as defined by a T score of -2.5 or less, and 45 patients (50.6%) had
      osteopenia (T score -1.0 to -2.5). In the subset of 53 patients who also had the
      BMD of the radius measured, the results of the BMD of the radius changed the
      category of diagnosis in 18 patients (34%). The prevalence of osteoporosis
      increased from 25% to 53% when the results of the radius were included.
      CONCLUSIONS: Men with prostate cancer treated with ADT have a high prevalence of
      osteopenia and osteoporosis as determined by peripheral and central BMD
      measurements. The use of the peripheral BMD measurement appears to identify more
      patients with osteoporosis and suggests its use in the evaluation of osteoporosis
      in men receiving ADT.

PMID- 16413353
TI  - Relationship between sexual dysfunction and psychiatric status in premenopausal
      women with fibromyalgia.
AB  - OBJECTIVES: To evaluate the possible relationship between the sexual and
      psychiatric status of premenopausal female patients with fibromyalgia compared
      with healthy controls. METHODS: A total of 48 female patients with fibromyalgia
      and 38 age-matched healthy controls were enrolled in the study. All the subjects
      were asked to complete the Female Sexual Function Index (FSFI) for sexual status
      and the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI)
      for psychiatric assessment. Serum biochemical analysis was done, and the serum
      hormonal levels were analyzed. RESULTS: The mean BDI score for patients was
      significantly greater than the score for the controls (P = 0.017) and the mean
      FSFI score was significantly lower than the score for the controls (P = 0.001).
      According to the FSFI data, female sexual dysfunction was found in 26 patients
      (54.2%) with fibromyalgia and only 6 controls (15.8%), a significant difference
      (Pearson chi-square = 14.46, P = 0.000). When the subscores of each domain of
      FSFI were evaluated, the most common sexual problem was diminished desire in
      patients (n = 30, 62.5%) and controls (n = 11, 28.9%). In the correlation
      analysis, the FSFI score showed a significant negative correlation with the BDI
      (r = -0.337, P = 0.002) and STAI (r = -0.413, P = 0.004) scores. No significant
      correlation was revealed between the FSFI and BDI or FSFI and STAI scores in the
      controls. CONCLUSIONS: Depression is one of the emotional disorders commonly
      encountered in women with fibromyalgia, most possibly leading to sexual
      dysfunction. Thus, sexual dysfunction related to impaired psychiatric status
      should be considered a common problem in premenopausal women with fibromyalgia.

PMID- 16413354
TI  - Value of frozen section analysis with suspected testicular malignancy.
AB  - OBJECTIVES: To determine whether frozen section analysis (FSA) assists safe
      conservative surgery for men presenting with suspected testicular tumors.
      METHODS: We performed a retrospective review of intraoperative testicular FSA
      used at a single university institution during an 11-year period. The exclusion
      criteria included lesions of paratesticular origin, size greater than 5 cm, and
      the known presence of elevated tumor markers or metastatic disease. RESULTS:
      Eighty men underwent FSA, facilitating the diagnosis of germ cell malignancy in
      51 (54.3%) of the 94 new cases encountered during this period. Malignancy was
      reported by FSA in 52 patients (65.0%), but was later revised in 3 to benign
      Leydig cell tumor after orchiectomy. Also, 2 of 27 specimens reported as benign
      by FSA were revised to malignant after analysis of paraffin-embedded tissue from
      the biopsies. Both were seminoma and required delayed orchiectomy. FSA was
      reported as "suspicious" (intratubular germ cell neoplasia with necrosis) in 1
      patient, in whom orchiectomy was performed and malignancy confirmed. In total,
      orchiectomy was avoided in 25 cases (31.3%). The positive and negative predictive
      value for FSA in the diagnosis of testicular malignancy was 94.2% and 92.6%,
      respectively. Of 13 lesions 1 cm or less, 10 (76.9%) were benign. All 26 lesions
      greater than 3 cm were malignant. A clear correlation between lesion size and the
      diagnosis of malignancy was demonstrated. CONCLUSIONS: FSA is a valuable tool
      assisting testicular preservation. Lesion size correlated with incidence of
      malignancy; therefore, FSA may be best used for small testicular lesions suitable
      for excision biopsy.

PMID- 16413355
TI  - Duplex ultrasonography detects clinically significant anomalies of penile
      arterial vasculature affecting surgical approach to penile straightening.
AB  - OBJECTIVES: To determine the frequency of aberrant penile arterial anatomy in men
      with Peyronie's disease (PD) and the potential impact on the surgical approach to
      penile straightening. METHODS: A retrospective analysis of 63 consecutive men
      undergoing penile duplex ultrasonography in preparation for penile straightening
      surgery was performed. They were compared with a group of 61 men with erectile
      dysfunction (ED) undergoing penile duplex ultrasonography during the same period.
      RESULTS: Arterial anomalies distal to the pubic symphysis were noted in 44% of
      men with PD and 46% of men with ED. The most common anomaly observed was crossing
      cavernosal arteries seen in 37% of the men with PD and 39% of the men with ED.
      Distal perforators of the dorsal artery supplying the cavernosal bodies were
      observed in 10% and 8% of the men with PD and ED, respectively. No difference was
      found in the overall frequency or type of arterial anomalies between the two
      groups. CONCLUSIONS: Men with PD have a high prevalence of arterial anomalies,
      including distal perforating arteries. Their preoperative evaluation should
      include duplex ultrasonography with delineation of the penile arterial anatomy.
      This will aid in surgical planning and potentially prevent maneuvers that may
      adversely affect the cavernosal blood supply and place the patient at risk of
      postoperative ED.

PMID- 16413356
TI  - Efficacy of extracorporeal shock wave lithotripsy for isolated lower caliceal
      stones in children compared with stones in other renal locations.
AB  - OBJECTIVES: To evaluate the efficacy of extracorporeal shock wave lithotripsy
      (ESWL) monotherapy for isolated lower caliceal calculi in a pediatric age group
      and compare it with that for isolated middle/upper caliceal and renal pelvic
      calculi. METHODS: We retrospectively reviewed the data of 151 renal units in 126
      children treated with ESWL for isolated caliceal and renal pelvic stones from
      March 1992 to February 2004. The stones were localized in the lower, middle/upper
      calices, and renal pelvis in 50, 26, and 75 renal units, respectively. The
      results were compared with respect to renal location and stone burden. RESULTS:
      The median patient age was 8 years (range 1 to 16). The median stone burden in
      the lower and middle/upper caliceal groups was significantly lower than in the
      renal pelvis group at 0.6, 0.6, and 1 cm2, respectively (P = 0.002). The overall
      stone-free rate was 62% for lower calices, 65.3% for middle/upper calices, and
      80% for renal pelvis stones. For the group with a stone size greater than 2 cm2,
      the stone-free rate decreased to 33% in both lower and middle/upper calices;
      however, it was almost the same in the renal pelvis (81.8%). A highly significant
      relation was found between the stone burden and number of sessions (P < 0.001),
      but none between the stone burden and stone-free rate. CONCLUSIONS: In our study,
      ESWL was equally effective for stones in all locations. We recommend ESWL as the
      primary treatment of choice for stones less than 2.0 cm2 in all caliceal
      locations. For the management of caliceal stones greater than 2.0 cm2,
      prospective randomized trials comparing ESWL and percutaneous nephrolithotomy are
      necessary.

PMID- 16413359
TI  - Prospective evaluation of inpatient and outpatient bladder training in children
      with functional urinary incontinence.
AB  - OBJECTIVES: To evaluate, in a prospective study, the effectiveness of a bladder
      training program. Daytime and/or nighttime wetting as a consequence of functional
      urinary incontinence is a common problem in childhood. Various treatment options
      are available, including with cognitive-behavioral "bladder training." METHODS:
      Sixty patients (age 8 to 12 years) with urge incontinence or dysfunctional
      voiding were evaluated. After a no-treatment control period (average 6 months),
      patients underwent a 6-day bladder training course, which was offered either as
      inpatient or outpatient training, leaving the choice to the patients' parents.
      Clinical assessments were recorded at the beginning of the control period, at
      training entry and training completion, and after 1 (inpatient training group
      only), 3, and 6 months. RESULTS: Six months after training completion, 64.1% and
      64.7% of the inpatient and outpatient groups with daytime wetting and 51.5% and
      17.7% of the inpatient and outpatient groups with nighttime wetting were cured or
      had improved, respectively. The spontaneous cure rate during the 6-month control
      period was 0% to 20.5%. Of the inpatient group with urge incontinence, the
      functional bladder capacity increased by 15%. The children aged 9 to 12 years in
      the inpatient group had significantly greater cure rates than the 8-year-old
      children. CONCLUSIONS: Compared with the control period, the bladder training
      program evaluated in this study resulted in significantly greater success rates.
      The results lead to the assumption that children with nighttime wetting treated
      in the inpatient training will succeed better than those in outpatient training.
      The cure and improvement rates of daytime wetting were greater than those for
      nighttime wetting.

PMID- 16413360
TI  - Is one-day hospitalization after open pyeloplasty possible and safe?
AB  - OBJECTIVES: A critical pathway was developed to determine whether open
      pyeloplasty could be performed in preadolescent and adolescent children with
      ureteropelvic junction (UPJ) obstruction with patients safely discharged after a
      1-day hospitalization. METHODS: Twenty-six consecutive children who underwent
      open dismembered pyeloplasty for the treatment of UPJ obstruction and followed a
      critical pathway for preoperative education, operative management, and
      postoperative care were evaluated. The patients received a caudal anesthetic for
      preventive analgesia unless not technically possible and postoperative ketorolac
      (Toradol) unless contraindicated. A child was required to fulfill five strict
      criteria to be discharged from the hospital. RESULTS: The 26 patients with UPJ
      obstruction consisted of 18 boys and 8 girls (age range 2.4 months to 16.7
      years). Of the 26 patients, 24 (92%) were discharged on the first postoperative
      day, with a mean length of hospitalization of 1.1 days (range 1 to 3). All
      patients younger than 6 years of age (19 patients) were discharged on the first
      postoperative day. Of the 25 patients who received a caudal block, 24 (96%) were
      discharged on the first postoperative day. All patients tolerated the procedure
      well without major complications. CONCLUSIONS: This is the first study, to our
      knowledge, to describe a detailed critical pathway for open pyeloplasty to treat
      UPJ obstruction. This enabled all children younger than 6 years of age and more
      than 90% of all patients to be discharged uniformly on the first postoperative
      day.

PMID- 16413361
TI  - Neurovascular preservation in female orthotopic radical cystectomy significantly
      improves sexual function.
AB  - Radical cystectomy has emerged as a standard treatment option for patients with
      muscle invasive bladder cancer. The impact of nerve-sparing cystectomy with
      urethra and vaginal sparing has not been quantified with validated
      questionnaires. We report our experience with nerve-sparing orthotopic radical
      cystectomy and the impact on postoperative sexual function.

PMID- 16413362
TI  - Use of pedicled tunica vaginalis flap in elaborated perineal approach for
      bulboprostatic anastomotic urethroplasty.
AB  - We describe the use of a pedicled tunica vaginalis flap to cover the anastomotic
      area after progressive elaborated perineal bulboprostatic anastomotic
      urethroplasty. Urethroplasty is completed in the standard technique. The tunica
      is opened longitudinally and dissected away as a rectangular flap from the testis
      and wrapped around the urethra.

PMID- 16413363
TI  - Use of titanium knot placement device (TK-5) to secure dorsal vein complex during
      laparoscopic radical prostatectomy and cystoprostatectomy.
AB  - INTRODUCTION: We evaluated the feasibility and describe the surgical technique of
      using the Ti-Knot device TK-5 to secure the dorsal vein complex (DVC) during 20
      consecutive cases of laparoscopic radical prostatectomy and cystoprostatectomy.
      TECHNICAL CONSIDERATIONS: Bloodless DVC ligation and transection was successfully
      achieved in 19 (95.03%) of 20 cases. In only 1 case, venous bleeding occurred
      after DVC transection. However, in this case, the two stitches used to ligate the
      DVC were tightly tied, and the bleeding probably occurred because the stitches
      were passed too superficially on the DVC. In another case, a third stitch had to
      be placed and tied with the aid of the Ti-Knot device because the second 2-0
      Vicryl stitch placed at the DVC broke. In only 1 case did we experience some
      degree of trouble with the knotting process because one of the ends of the Vicryl
      suture slipped back into the abdominal cavity. The time to tie each suture with
      the Ti-Knot device, defined after the moment the needle was passed underneath the
      DVC to the moment the titanium knot was crimped and the Vicryl suture trimmed,
      was less than 1 minute (median 50 seconds, range 45 to 56) in all cases, except
      the case described above. No cases of the Ti-Knot device misfiring or malfunction
      occurred in this series. CONCLUSIONS: In our experience, the Ti-Knot titanium
      knot placement device proved to be safe and efficient during laparoscopic
      ligation and control of the DVC.

PMID- 16413364
TI  - Rectourethral fistula associated with two short segment urethral strictures in
      the anterior and posterior urethra: single-stage reconstruction using buccal
      mucosa and a radial forearm fasciocutaneous free flap.
AB  - INTRODUCTION: We report a novel surgical technique used to repair a rectourethral
      fistula associated with two short-segment urethral strictures located in the
      anterior and posterior segments of the urethra in a patient with prior
      unsuccessful repairs. TECHNICAL CONSIDERATIONS: The anterior urethral stricture
      was reconstructed with a ventral onlay of buccal mucosa in the exaggerated
      lithotomy position. In a modified prone position, the rectourethral fistula was
      repaired using the transrectal transsphincteric (York-Mason) technique and the
      posterior urethral stricture with a radial forearm fasciocutaneous free flap
      which was anastomosed to the inferior gluteal artery and vein. The coexistence of
      a rectourethral fistula and distal urethral stricture requires simultaneous
      repair, because the urethral pressure from the distal obstruction may compromise
      fistula closure. Reconstructive efforts should be tailored to minimize disruption
      of the urethral blood supply in patients with previous pelvic trauma. Rectal and
      urethral repairs should be separated by well-vascularized tissue to prevent
      fistula recurrence. CONCLUSIONS: The radial fasciocutaneous flap may offer the
      reconstructive surgeon another surgical option for complex urethral stricture and
      rectourethral fistula reconstruction when the local blood supply is in question.
      Longer follow-up and more cases are needed to further evaluate the continued use
      of this technique.

PMID- 16413366
TI  - Giant unilateral abdominoscrotal hydrocele in association with crossed testicular
      ectopia.
AB  - Abdominoscrotal hydrocele and transverse testis ectopia are rare clinical
      conditions. This case report describes the combination of these two rare
      entities. An azoospermic and infertile adult man presented with left
      abdominoscrotal hydrocele and a right impalpable testis. He was treated with left
      orchiopexy, right orchiectomy, and excision of the abdominoscrotal hydrocele. We
      discuss the diagnosis and treatment of this combination, which has not been
      previously reported.

PMID- 16413365
TI  - Primary squamous cell carcinoma in unreconstructed exstrophic bladder.
AB  - Bladder exstrophy is associated with an increased incidence of primary
      adenocarcinoma of the bladder. We report a rare case of squamous cell carcinoma
      occurring in the unreconstructed, exstrophic bladder of a 53-year-old woman
      treated with radical cystectomy and radiochemotherapy. This case represents the
      oldest patient to present with squamous cell carcinoma of an unreconstructed
      exstrophic bladder. We discuss the potential mechanisms of carcinogenesis in this
      patient, noting how they may potentially differ from those in a patient with a
      reconstructed bladder.

PMID- 16413367
TI  - Percutaneous ultrasound-guided radiofrequency ablation of recurrent renal cell
      carcinoma in renal allograft after partial nephrectomy.
AB  - Percutaneous thermal ablation is increasingly being studied in the treatment of
      renal tumors. Because radiofrequency ablation is a minimally invasive and nephron
      sparing procedure, it is ideally suited for patients with a single kidney,
      multiple tumors, or contraindications to conventional surgery. We report on a
      patient with recurrent renal cell carcinoma in a transplanted kidney that was
      successfully treated with percutaneous ultrasound-guided radiofrequency ablation.

PMID- 16413369
TI  - Novel use of da Vinci Robotic Surgical System: removal of seminal vesicle cyst in
      previously dissected pelvis.
AB  - We report a novel use of the da Vinci Robotic Surgical System to remove a seminal
      vesicle cyst in a previously dissected pelvis.

PMID- 16413368
TI  - Metastatic renal cell carcinoma to the nose and ethmoid sinus.
AB  - We report a rare case of metastatic renal cell carcinoma involving the nose and
      ethmoid sinus, 17 years after initial nephrectomy and diagnosis of Stage T1N0
      clear cell renal cell carcinoma. The patient complained of nasal obstruction and
      epistaxis. Intensity-modulated radiotherapy (IMRT) was delivered using a higher
      than-conventional daily fraction size concurrently with interferon and
      thalidomide. The patient achieved a complete response both clinically and by
      magnetic resonance imaging, without any side effects. Late and rare sites of
      recurrences and treatment options are discussed.

PMID- 16413370
TI  - Robotic-assisted laparoscopic retroperitoneal lymph node dissection.
AB  - Minimally invasive laparoscopic techniques have been applied to the staging and
      treatment of testicular cancer during the performance of retroperitoneal lymph
      node dissection. The da Vinci Surgical System potentially improves the safety and
      accuracy of this approach. We present what we believe to be the first published
      description of robotic-assisted retroperitoneal lymph node dissection, which was
      performed in an 18-year-old man with a mixed germ cell tumor. This case
      demonstrates the technical feasibility, safety, and accuracy of robotic-assisted
      retroperitoneal lymph node dissection and expands the role of minimally invasive
      techniques in urologic oncology.

PMID- 16413371
TI  - Laparoscopic pyeloplasty and pyelopyelostomy for ureteropelvic junction
      obstruction in a duplicated collecting system.
AB  - Ureteropelvic junction obstruction can be associated with renal anomalies. We
      present a case of symptomatic ureteropelvic junction obstruction associated with
      a duplicated collecting system that was successfully treated by laparoscopic
      pyeloplasty and concomitant pyelopyelostomy. The operative time was 210 minutes,
      and the blood loss was 20 mL. The inpatient stay was 4.5 days, and the patient
      returned to work after 28 days. Subsequent renograms confirmed improvement in
      renal function and resolution of obstruction. After 1 year, the patient remained
      asymptomatic. This is a feasible minimally invasive procedure for this condition
      that requires advanced reconstructive and intracorporeal suturing skills.

PMID- 16413372
TI  - Early recurrence of primary focal segmental glomerulosclerosis in an older
      cadaveric renal allograft recipient resistant to plasmapheresis.
AB  - We report an unusual case of recurrent primary focal segmental glomerulosclerosis
      in an apparent low-risk cadaveric renal allograft recipient only 2 days after
      transplantation, who did not respond to repeated courses of plasmapheresis.

PMID- 16413373
TI  - Transitional cell carcinoma associated with marijuana: case report and review of
      the literature.
AB  - Transitional cell carcinoma of the bladder tends to occur in older patients with
      a history of tobacco use. We recently evaluated and treated a 45-year-old man
      with a history of heavy marijuana use. The patient's only risk factor for
      transitional cell carcinoma was the inhalation of up to five marijuana cigarettes
      daily for more than 30 years. We present our case and review the literature.

PMID- 16413374
TI  - Testicular presentation of sarcoidosis and organ preservation: case report and
      review of management strategies.
AB  - We report the case of a 24-year-old Cuban-American man initially presenting with
      a 1-year history of bilateral testicular pain, subsequently diagnosed as
      sarcoidosis. The diagnosis was histologically confirmed intraoperatively with
      excisional biopsy of the right tunica. Genitourinary complaints are a rare
      initial presentation of this disease. Although therapeutic approaches have varied
      in published reports, no definitive protocol for treatment has been established.
      We suggest confirmation of the diagnosis, followed by symptomatic treatment,
      reserving orchiectomy and steroid therapy for severe, refractory, or disseminated
      cases.

PMID- 16413375
TI  - Decreased inhibitory activity of prothrombin to calcium oxalate crystallization
      by specific chemical modification of its gamma-carboxyglutamic acid residues.
AB  - OBJECTIVES: To investigate the inhibitory role of gamma (gamma)-carboxyglutamic
      acid (Gla) in the Gla domain of urinary prothrombin in the formation of calcium
      oxalate crystals. METHODS: Morpholine and formaldehyde at different
      concentrations were added to the solution of prothrombin to cause the conversion
      of Gla to gamma-methyleneglutamic acid (MGlu). The extent of the modification was
      controlled by the relative amount of modification reagents to prothrombin. The
      100-fold molar excess of modification reagents to prothrombin produced the
      prothrombin molecule containing 2gamma-MGlu residues, and the 10,000-fold molar
      excess produced the molecule containing 8gamma-MGlu residues. The inhibitory
      activities of prothrombin and modified prothrombin to calcium oxalate
      crystallization were evaluated by the seeded crystallization technique. RESULTS:
      The inhibitory index of Gla prothrombin to calcium oxalate crystallization was
      14.2%, that of 2gamma-MGlu prothrombin was 12.8%, decreased by about 10%, and
      that of 8gamma-MGlu prothrombin was 5.0%, decreased by about 65%. CONCLUSIONS:
      The Gla in the Gla domain of urinary prothrombin may play an important role in
      inhibiting the formation of renal calcium oxalate calculus.

PMID- 16413376
TI  - Expression of c-jun oncogene in hyperplastic and carcinomatous human prostate.
AB  - OBJECTIVES: To investigate c-jun oncoprotein (JUN) expression in diseases of the
      human prostate gland at the tissue level and to determine its relationship to
      clinicopathologic variables. METHODS: The expression of JUN was studied using
      immunohistochemistry in archival tissue from benign prostatic hyperplasia (BPH)
      (n = 16) and prostate adenocarcinoma (PCa) (n = 36) specimens. RESULTS: JUN
      specific positive nuclear immunostaining was observed in 13 (81.25%) of 16 BPH
      and 31 (86.1%) of 36 PCa specimens. JUN-specific immunostaining was significantly
      stronger in the PCa than in the BPH tissue (P = 0.006). In the PCa tissue, no
      significant correlation was found between JUN immunohistochemical expression and
      tumor histologic grade (Gleason score) or serum prostate-specific antigen level.
      CONCLUSIONS: JUN expression may play a role in normal cell function of the
      prostatic epithelium and is expressed in most BPH and PCa samples. The finding
      that JUN-specific immunostaining intensity was stronger in the vast majority of
      PCa than in the BPH samples implies that the role of c-jun may be enhanced during
      malignant transformation.

PMID- 16413377
TI  - Enhanced binding of modified pentosan polysulfate and heparin to bladder--a
      strategy for improved treatment of interstitial cystitis.
AB  - OBJECTIVES: To attach galactosyl residues to pentosan polysulfate (PPS) and
      heparin so that these drugs will bind to the endogenous lectins in the bladder.
      The increased binding may improve their efficacy for treating interstitial
      cystitis. METHODS: The anionic polysaccharides, PPS, and heparin were modified by
      attachment of lactose. The covalent modification was by chemical linking of
      lactose derivatives or by beta-lactosyl transfer reaction from p-nitrophenyl beta
      lactoside using the transglycosylation activity of Trichoderma reesei cellulase
      enzymes. The unmodified and modified PPS and heparin, as well as various mucin
      glycoproteins, were radiolabeled or biotinylated and examined for their ability
      to bind to rabbit and human bladder. RESULTS: Both biotinylated and radiolabeled
      PPS and heparin bound very weakly or not at all to human and rabbit bladders. In
      contrast, the PPS and heparin modified by attachment of lactose, as well as the
      asialo mucin glycoproteins, bound strongly to human and rabbit bladders. This
      binding is apparently mediated by the interaction of the endogenous bladder
      galactins and the non-reducing galactose terminals in the lactose attached to the
      anionic polysaccharides or the asialoglycoproteins. CONCLUSIONS: Lactose-pentosan
      sulfate and lactose-heparin bind more avidly to the bladder epithelium than the
      unmodified molecules. Thus, they may be more effective for interstitial cystitis
      than the parent drugs. Other possible applications of this approach include
      modification of intravesical chemotherapeutic agents for bladder cancer, or
      intravesically placed antibiotics, to improve their adherence and retention in
      the bladder.

PMID- 16413378
TI  - Human detrusor smooth muscle cells release interleukin-6, interleukin-8, and
      RANTES in response to proinflammatory cytokines interleukin-1beta and tumor
      necrosis factor-alpha.
AB  - OBJECTIVES: Recently, we have demonstrated that human detrusor smooth muscle
      cells in culture secrete the chemokine monocyte chemoattractant protein 1. In the
      present study, we extended these studies to include the effect of the
      proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)
      1beta on IL-8, IL-6, and RANTES (regulated on activation, normal T cell expressed
      and secreted) release by human detrusor smooth muscle cells (HDSMCs) and examined
      their regulation. METHODS: With ethical approval, detrusor muscle biopsies were
      obtained from patients with benign noninvasive bladder diseases undergoing
      control cystoscopy. HDSMCs were cultured using an explant technique and used at
      maximum third passage. HDSMCs were cultured in the presence or absence of TNF
      alpha and IL-1beta. Supernatants were collected after 6, 12, and 24 hours. IL-8,
      IL-6, and RANTES were measured using enzyme-linked immunosorbent assays. RESULTS:
      TNF-alpha and IL-1beta (0.01 to 100 ng/mL) induced secretion of IL-8, IL-6, and
      RANTES in a dose and time-dependent manner. The production of chemokines reached
      a maximum after 24 hours of incubation. In nonstimulated HDSMCs, the basal
      secretion of IL-8, IL-6, and RANTES was detectable. Induction of cytokine release
      by IL-1beta was synergistic with TNF-alpha. CONCLUSIONS: These findings for the
      first time demonstrate that HDSMCs release IL-8, IL-6, and RANTES in response to
      IL-1beta and TNF-alpha. The constitutive and cytokine-stimulated production of
      chemokines and cytokines suggest that the human detrusor may contribute to mast
      cell infiltration into the bladder interstitium. The new evidence that HDSMCs
      secrete immunomodulatory proteins makes the detrusor muscle cell a target for
      anti-inflammatory therapy.

PMID- 16413379
TI  - Effect of maturation and aging on response of rabbit bladder to bilateral in vivo
      ischemia/reperfusion.
AB  - OBJECTIVES: To evaluate the impact of maturation and aging on the effect of
      bilateral in vivo ischemia/reperfusion on bladder function. METHODS: Male rabbits
      were separated into three groups by age: immature, mature, and aged rabbits; and
      each group was subdivided into five subgroups. Each rabbit was subjected to 2
      hours of bilateral ischemia. After ischemia, the rabbits in subgroup 1 were
      killed immediately; the other subgroups were allowed to recover for 1, 7, or 14
      days. Separate control (sham-operated) subgroups were not subjected to ischemia.
      At the end of the experimental period, the bladder was excised, body and base
      separated, and two strips were prepared from each and mounted in individual
      baths. The contractile responses to field stimulation and carbachol, adenosine
      triphosphate, and potassium chloride were determined for the body. The responses
      to field stimulation alone were determined for the base. RESULTS: The rabbit body
      and bladder weights of the mature and aged rabbits were significantly greater
      than that of the young rabbits, but not different from each other. The mature
      rabbits were significantly more sensitive to ischemia/reperfusion than were the
      young rabbits. Finally, the aged rabbits were slightly more sensitive to
      ischemia/reperfusion than the mature rabbits. CONCLUSIONS: The results of our
      study have shown that the sensitivity of the bladder to ischemia/reperfusion
      injury increases with age. A very significant increase was found in the
      sensitivity between young and mature rabbits, with a significantly smaller
      increase in sensitivity between mature and old rabbits.

PMID- 16413381
TI  - Contrast-enhanced cardiac magnetic resonance in the evaluation of myocardial
      infarction and myocardial viability in patients with ischemic heart disease.

PMID- 16413382
TI  - A cross-sectional examination of age and physical activity on performance and
      event-related brain potentials in a task switching paradigm.
AB  - Younger and older physically active and sedentary adults participated in a task
      switching paradigm in which they performed a task repeatedly or switched between
      two different tasks, while measures of response speed, response accuracy, P3
      amplitude, and P3 latency were recorded. Overall, response times were faster and
      midline P3 amplitudes were larger for the active than for the sedentary
      participants. P3 latencies discriminated between active and sedentary individuals
      on trials in which multiple task sets were maintained in memory and task switches
      occurred unpredictably but not in blocks of trials in which a single task was
      repeatedly performed. Results are discussed in terms of the specificity and
      generality of physical activity effects on cognition.

PMID- 16413383
TI  - A response to Haigh (2005): where are the keynote debates in nurse education?

PMID- 16413384
TI  - The new face of bispecific antibodies: targeting cancer and much more.
AB  - The term magic bullet was first coined by bacteriologist Paul Ehrlich in the late
      1800s to describe a chemical with the ability to specifically target
      microorganisms while sparing normal host cells. His concept was later expanded to
      include treatments for cancer, but it is only in recent decades, with development
      and improvements in monoclonal antibody (mAb) technology, that the full
      therapeutic implications of "magic bullet" strategies have been realized.
      Expanding on the success of mAb-targeting, linking the specificity of two mAbs
      into a single agent, called a bispecific antibody (BiAb), allows for targeting of
      a therapeutic biological agent or cell to specific tissue antigens. Classically,
      BiAbs have been used for several decades to redirect cytotoxic T cells or other
      effector cells to kill tumor cells. Here, we review preclinical models and
      ongoing phase I clinical trials in which arming polyclonally activated T cells
      with BiAbs may provide anti-tumor activity without dose-limiting toxicities.
      Additionally, we review findings from this novel strategy that merges magic
      bullet technology with hematopoietic stem cells to repair injured myocardium.
      Arming stem cells with BiAbs directed at injury-associated antigens enhances
      specific homing and engraftment to myocardial infarctions and may significantly
      improve cardiac function, strongly suggesting new paradigms for BiAb-targeting
      applications in tissue repair.

PMID- 16413385
TI  - Bone marrow mesenchymal stem cells chimerism after allogeneic hematopoietic
      transplantation.

PMID- 16413386
TI  - Acetylsalicylic acid-induced release of HSP70 from mast cells results in cell
      activation through TLR pathway.
AB  - OBJECTIVE: Mast cells are considered major players in IgE-mediated allergic
      responses, but have also recently been recognized as active participants in
      innate as well as specific immune responses. Heat stress can modulate innate
      immunity by inducing stress proteins such as heat shock proteins (HSPs). It has
      been reported that HSPs are capable of inducing the production of pro
      inflammatory cytokines by the monocyte-macrophage system. In the current study,
      we explored whether the stress response induces HSPs and affects the signaling
      pathways of mast cells. METHODS: In mouse mast cells, derived from a culture of
      bone marrow cells of male BALB/cBy and null HSF-1(-/-) mice, responsiveness to
      exogenous and endogenous HSP70 was monitored by measuring cytokine release.
      RESULTS: Using BMMC, we show that treatment with heat shock or acetylsalicylic
      acid results in a selective induction of HSPs, and leads to release of HSP70 into
      the extracellular environment. The release of HSP70 from mast cells may be of
      functional importance. We found that after induction of HSP70, the production of
      TNF-alpha and IL-6 was increased. In a number of experiments, we demonstrated
      that exogenous/secreted HSP70 is most likely responsible for the activation of
      mast cells to produce cytokines. Extracellular HSP70 induced production of TNF
      alpha and IL-6 through the activation of the TLR4 receptor pathway, which was
      evidenced by an abrogation of the response in mast cells cultured from TLR4(null)
      or HSF-1(-/-) mice. CONCLUSION: Our experiments suggest that stress conditions
      can induce pro-inflammatory cytokine production by mast cells through an
      autocrine or paracrine stimulation of TLR receptors after a heat shock response.
      The recognition that heat shock proteins induce mast cell activation suggests an
      involvement of these cells in the immunological processes induced by heat shock
      response.

PMID- 16413387
TI  - Chemokine expression in human erythroid leukemia cell line AS-E2: macrophage
      inflammatory protein-3alpha/CCL20 is induced by inflammatory cytokines.
AB  - OBJECTIVE: Normal and malignant hematopoietic cells are shown to express and
      secrete various cytokines and chemokines, some of which are believed to play an
      important role in normal and abnormal hematopoiesis in an autocrine/paracrine
      manner. To explore the possibility of a cytokine/chemokine network participating
      in the pathophysiology of anemic disorders, we evaluated the ability of
      inflammatory cytokines to induce chemokine expression using erythroid progenitor
      cells. METHODS: Erythropoietin-dependent human leukemia cell line AS-E2 was used
      as a model of erythroid colony-forming unit (CFU-E) cells. The expression of mRNA
      of 8 chemokines was examined using RT-PCR, before and after TNF-alpha, IFN-gamma,
      and IL-1beta stimulation. For MIP-3alpha, the promoter activity was analyzed by
      luciferase assay and secretion was confirmed by ELISA. The expression of CCR6,
      the specific receptor for MIP-3alpha, was analyzed by RT-PCR and flow cytometry.
      RESULTS: Unstimulated AS-E2 cells constitutively expressed transcripts for MCP-4,
      IP-10, PF-4, IL-8, and MIP-3alpha. Stimulation with TNF-alpha, IFN-gamma, and IL
      1beta upregulated MIP-3alpha mRNA expression and induced its protein secretion.
      Luciferase assay revealed that these cytokines could upregulate promoter activity
      of the MIP-3alpha gene, possibly through the NF-kappaB pathway. CCR6 mRNA was
      detected and its intracellular expression was confirmed. CONCLUSION: These data
      suggest that inflammatory cytokine-stimulated erythroid progenitors secrete MIP
      3alpha, which may function in an autocrine/paracrine manner. Furthermore, the
      existence of intracellular CCR6 suggests the involvement in cytokine signaling of
      a MIP-3alpha-dependent internal autocrine mechanism. These mechanisms may play a
      role in pathophysiology of anemic disorders, such as secondary anemia and bone
      marrow failure syndromes.

PMID- 16413388
TI  - Regulation of primitive hematopoiesis in zebrafish embryos by the death receptor
      gene.
AB  - OBJECTIVE: We investigated the regulatory mechanism of primitive hematopoiesis in
      zebrafish (Danio rerio) embryos with particular reference to the role of a death
      receptor (zDR) gene, based on a morpholino (MO) knockdown approach. METHODS: MOs
      targeting the zDR and chordin (Chd) were injected into naturally spawned embryos
      at one- to four-cell stage. A random sequence (RS) MO was used as a control.
      Effects on hemoglobin formation (Hb), apoptosis, and lineage-specific gene
      expression were examined. Embryos injected with zDR, Chd, and RS-MOs were denoted
      zDR(mo), zChd(mo), and zRS(mo), respectively. Those co-injected with Chd+zDR-MOs
      and Chd+RS-MOs were abbreviated zChd+DR(mo) and zChd+RS(mo). RESULTS: zDR mRNA
      expression was restricted to the intermediate cell mass of wild-type (WT) and
      zChd(mo) embryos. At 48 hours postfertilization, zDR(mo) embryos showed increased
      Hb compared with WT or zRS(mo) embryos (2.36 x 10(-2) +/- 1.13 x 10(-3) vs 1.85 x
      10(-2) +/- 5.60 x 10(-4) vs 1.79 x 10(-2) +/- 1.31 x 10(-3) U, p < 0.05).
      zChd+DR(mo) embryos also showed increased Hb compared with zChd(mo) or
      zChd+RS(mo) embryos (4.60 x 10(-2) +/- 2.79 x 10(-3) vs 3.17 x 10(-2) +/- 1.07 x
      10(-3) vs 3.05 x 10(-2) +/- 1.25 x 10(-3) U, p < 0.05). zDR-MO reduced apoptosis,
      as shown by reduced terminal transferase-mediated dUTP nick end-labeling staining
      in zChd+DR(mo) compared with zChd+RS(mo) embryos and caspase-3 activity in
      zDR(mo) vs zRS(mo) (0.525 +/- 0.094 vs 0.953 +/- 0.113 U, p < 0.05), and
      zChd+DR(mo) vs zChd+RS(mo) embryos (0.247 +/- 0.121 vs 1.180 +/- 0.082, p <
      0.05). zChd+DR(mo) embryos showed upregulation of erythroid-specific embryonic
      hemoglobin gene expression but not that of a myeloid-specific myeloperoxidase
      gene. CONCLUSION: Knockdown of zDR in zebrafish embryos decreased apoptosis and
      increased Hb, suggesting that zDR may regulate primitive hematopoiesis during
      development.

PMID- 16413389
TI  - A pharmacodynamic study of 5-azacytidine in the P39 cell line.
AB  - OBJECTIVE: 5-azacytidine (azacytidine), a DNA hypomethylating agent, was recently
      approved as the first therapeutic agent for the treatment of myelodysplastic
      syndromes. The present subcutaneous dosing schedule, 75 mg/m(2) for 7/28 days, is
      based on early clinical studies and may constitute a practical problem for
      patients. The present in vitro study aimed at evaluating the pharmacodynamics of
      azacytidine, thereby providing a rationale for clinical dose-finding studies.
      METHODS: P39 cells were incubated with 0.1, 0.5, and 1 microM azacytidine daily
      for 24, 48, and 72 hours, followed by 48 hours in drug-free medium. The effects
      of azacytidine on cell growth, proliferation, apoptosis, cell cycle status, and
      promoter methylation of E-cadherin, ER, and HIC genes were studied. RESULTS:
      Azacytidine decreased cell growth and proliferation, increased apoptosis, and
      affected cell cycle status in a dose-dependent manner. However, the exposure
      time, 24 to 72 hours, at doses between 0.5 and 1 microM, did not significantly
      affect any of these variables. Using first-order exponential pharmacokinetic
      model, we found that the effect of 1, 2, or 3 microM over 24 hours did not differ
      from that of 0.5 to 1 microM given over 48 to 72 hours. Induction of promoter
      hypomethylation was observed already after 24 hours of exposure with >or=0.5
      microM azacytidine with no clear dose-effect relationship. CONCLUSION: Our
      results indicate that optimal cellular effects of azacytidine might be achieved
      by shorter exposure times. The model provides information about the relation
      between azacytidine dose intensity and exposure time on malignant myeloid cells,
      which could serve as a rationale for further clinical development of practical,
      safe, and cost-effective dosing schedules.

PMID- 16413390
TI  - MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia
      by CD8+ autologous T lymphocytes.
AB  - OBJECTIVE: Tumor-associated antigens (TAA) are the basis for antigen-specific
      immunotherapy. The human homolog of the murine double-minute 2 oncoprotein (MDM2)
      is a putative TAA because it is overexpressed in several malignancies, including
      chronic lymphocytic leukemia (CLL) cells compared with normal B lymphocytes.
      PATIENTS AND METHODS: Autologous, MDM2-specific human leukocyte antigen (HLA)-A2
      restricted T cells were identified using interferon (IFN)-gamma-ELISPOT assays
      and HLA-A2/dimer-peptide staining after 4 weeks of in vitro culture. RESULTS:
      Using native CLL cells as antigen-presenting cells (APCs), we demonstrate the
      generation of MDM2-specific T cells in 7/12 CLL patients that recognized
      specifically the MDM2-derived peptide MDM2(81-88) bound to HLA-A2-dimers while
      they were inactive against an unrelated MAGE-3 peptide (p = 0.002). After 4
      weeks, up to 32.3% of the expanded CD8(+) T cells specifically recognized MDM2(81
      88) by HLA-A2-dimer/peptide staining and up to 0.9% of all T cells expanded
      reacted specifically against this MDM2-derived peptide in the IFN-gamma-ELISPOT
      assay. If T cells were not expandable using native CLL cells as APC, leukemic
      cells were stimulated with CD40-ligand to increase the antigen-presenting
      capacity. This resulted in successful generation of MDM2-specific T cells in
      three of five remaining cases tested. Additionally, the factor that correlated
      best with successful generation of antigen-specific T cells in CLL patients was
      the ability of APCs to secrete IFN-gamma upon stimulation. CONCLUSION: In
      summary, MDM2(81-88) was shown for the first time in humans to elicit a
      functional autologous immune response. MDM2 was demonstrated to be naturally
      processed and presented as TAA in primary human CLL cells enabling expansion of
      functional autologous tumor-specific T cells.

PMID- 16413391
TI  - Granulocyte colony-stimulating factor enhances the in vitro cytotoxicity of
      gemtuzumab ozogamicin against acute myeloid leukemia cell lines and primary blast
      cells.
AB  - OBJECTIVE: To evaluate the effects of granulocyte colony-stimulating factor (G
      CSF) on the in vitro sensitivity of acute myeloid leukemia (AML) cell lines and
      primary AML blast cells to gemtuzumab ozogamicin (GO). MATERIALS AND METHODS: AML
      cell lines and primary blasts from 10 patients with AML were first incubated for
      72 hours in the presence of G-CSF (5 or 100 ng/mL) and then exposed to increasing
      concentrations of GO (1-1,000 ng/mL) for an additional 72 hours. RESULTS:
      Pretreatment with G-CSF translated into significant enhancement of GO-induced
      cytotoxicity in the GO-sensitive HL-60 and NB-4 cells. Conversely, the response
      of GO-insensitive KG-1a, TF-1, and K562 cells was unaffected by in vitro priming
      with G-CSF. In vitro exposure to G-CSF augmented GO-induced apoptosis in 7 of 10
      primary AML samples and rendered blast cells from three refractory patients
      sensitive to killing effect of GO. The G-CSF-induced increase of the cytocidal
      activity of GO was independent of effects on the cell cycle and on the expression
      levels of CD33 antigen. Of potential interest, G-CSF induced dose-dependent
      inhibition of P-glycoprotein (P-gp/ABCB1) function in the GO-sensitive HL-60 and
      NB-4 cells and in blasts from three patients with AML that we tested. CONCLUSION:
      Collectively, our findings point to G-CSF as a potential sensitizing agent that
      can be exploited therapeutically to improve the clinical efficacy of GO.

PMID- 16413392
TI  - Tolerance induction by third-party "off-the-shelf" CD4+CD25+ Treg cells.
AB  - OBJECTIVE: Recent reports have shown that donor or host CD4(+)CD25(+) Treg cells
      can be used to control GVHD or graft rejection following allogeneic BMT in mice.
      In the present study we investigated the potential of third-party Treg cells
      compared to donor-type cells to facilitate BM allografting. METHODS: Graft
      rejection is assessed in a mouse model of T cell-mediated BM allograft rejection.
      Lethally irradiated C3H mice are transplanted at day 2 after irradiation with T
      cell-depleted Balb/Nude BM. Graft rejection is induced by purified host-type T
      cells infused one day prior to BMT. Cells tested for their facilitating activity
      are added to the T cell-depleted BM allograft. RESULTS: Naive or ex vivo-expanded
      third-party Treg cells can effectively enhance engraftment of T cell-depleted BM
      allografts, exhibiting reactivity in vitro and in vivo similar to that found for
      donor-type Treg cells. CONCLUSION: The use of third-party Treg cells in contrast
      to donor-type cells could allow advanced preparation of a large bank of Treg
      cells (off-the-shelf), with all the appropriate quality controls required for
      cell therapy.

PMID- 16413393
TI  - BMP-6 inhibits human bone marrow B lymphopoiesis--upregulation of Id1 and Id3.
AB  - OBJECTIVE: In mammals, factors produced by bone marrow (BM) stromal cells are
      instrumental in orchestrating the developmental process of B lymphocytes. Bone
      morphogenetic proteins (BMPs) are multifunctional cytokines previously found to
      regulate hematopoietic stem cells. In the present study, we have explored the
      role of BMP-6 in human B progenitor cells. MATERIALS AND METHODS: In vitro B
      lymphopoiesis of CD10(+) B progenitor cells from human BM was evaluated in the
      presence or absence of BMP-6 in short- or long-term coculture on MS-5 stromal
      cells, by tracking CFSE-labeled CD10(+) B progenitor cells or by quantification
      of CD19(+) cells. DNA synthesis in the pre-B cell line Nalm-6 was measured by
      (3)H-thymidine incorporation. BMP-6-induced phosphorylation of Smad1/5/8 was
      determined by Western blot analysis, whereas elevation of Id1-Id4 mRNA levels and
      basal BMP-6 mRNA levels were measured by real-time and conventional RT-PCR,
      respectively. RESULTS: By in vitro coculture of CD10(+) B progenitor cells or
      monoculture of Nalm-6 cells, we found that BMP-6 inhibited B lymphopoiesis by
      impeding cell proliferation. Furthermore, in CD10(+) B progenitors as well as in
      Nalm-6 cells, BMP-6 rapidly induced phosphorylation of Smad1/5/8, followed by an
      upregulation of Id1 and Id3 mRNA levels. Finally, we demonstrated that human bone
      marrow stromal cells express BMP-6 mRNA whereas B progenitor cells did not.
      CONCLUSIONS: We suggest that BMP-6, produced by the BM, may participate to fine
      tune the balance between proliferation, apoptosis, and differentiation in human B
      progenitor cells during BM B lymphopoiesis.

PMID- 16413394
TI  - The Mpl receptor expressed on endothelial cells does not contribute significantly
      to the regulation of circulating thrombopoietin levels.
AB  - OBJECTIVE: Blood levels of thrombopoietin (TPO) are regulated in part by cellular
      degradation following its binding to the cell surface receptor c-mpl. Previous
      reports have demonstrated that in addition to hematopoietic cells, c-mpl is
      expressed on and functions in several types of endothelial cells (ECs). We
      hypothesized that the c-mpl expressed on ECs would contribute to the regulation
      of circulating TPO levels. METHODS: To test this hypothesis we transplanted c-mpl
      null and wild-type (WT) control mice with WT marrow stem cells, resulting in two
      groups of posttransplant chimeric animals, one expressing c-mpl on megakaryocytes
      and platelets only and one in which the receptor is expressed on both
      hematopoietic and ECs. Should EC c-mpl take up TPO and degrade it, we predicted
      that c-mpl-null mice reconstituted with WT cells would display increased TPO
      levels and an increased steady state platelet count compared to the WT
      recipients. RESULTS: Contrary to our prediction, for up to 6 months
      posttransplantation both platelet counts and TPO levels in both groups of
      transplanted mice were virtually identical. CONCLUSIONS: Our results indicate
      that the EC c-mpl receptor does not contribute significantly to the regulation of
      TPO levels or to steady-state platelet counts. These results also imply that
      patients with congenital amegakaryocytic thrombocytopenia, lacking the c-mpl
      receptor, who have successfully been engrafted with normal hematopoietic stem
      cells should have normal (not elevated) TPO levels and that gene replacement
      strategies designed to restore c-mpl in these patients do not need to target ECs
      to establish the normal regulation of TPO.

PMID- 16413395
TI  - A preliminary investigation into the action of anagrelide: thrombopoietin-c-Mpl
      receptor interactions.
AB  - OBJECTIVE: Many studies have validated the clinical efficacy of anagrelide to
      reduce platelet counts in thrombocythemic conditions. With the ability to support
      human megakaryopoiesis in vitro using thrombopoietin (TPO), specific
      investigation of changes in platelet levels can be carried out in human systems.
      Using CD34(+) stem cells and murine BaF3 cells transfected with the human or
      murine TPO receptor, c-Mpl (BaF3mpl), the effect of anagrelide on cell
      differentiation, proliferation, and signaling was examined in the presence of
      TPO. METHODS: Inhibition of TPO-mediated cell differentiation by anagrelide was
      evaluated by fluorescein-activated cell sorting analysis. Cell proliferation was
      monitored by 3-(4,5-dimethylthiazol-2-yl)-5-3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) assays. Effect of anagrelide on TPO-mediated
      phosphotyrosine (pTyr) activity was examined by Western analysis of whole cell
      lysates. RESULTS: In the presence of TPO, anagrelide reduced the number of
      CD41(+) cells without a reduction in the total mononuclear cell number in a dose
      dependent manner. Growth inhibition was also observed in BaF3 cells transfected
      with human c-Mpl. Anagrelide also reduced TPO-specific pTyr activity in a species
      specific manner. No inhibitory effect could be demonstrated with interleukin-3
      stimulation. CONCLUSION: Parallel dose-response effects were found in both
      CD41(+) number and TPO-specific pTyr activity. These results suggest that
      anagrelide reduces TPO-mediated megakaryocyte proliferation of CD34(+) cells
      through a mechanism that leads to inhibition of intracellular signaling events.
      Furthermore, data also suggest that it is a species-specific effect, with no
      inhibitory activity against the murine receptor. Because there is a less than 10%
      difference in DNA sequence homology between human and murine receptors, the
      difference in sequence-specific activity must reside in these amino acid
      differences.

PMID- 16413396
TI  - In vitro transdifferentiation of adult bone marrow Sca-1+ cKit- cells cocultured
      with fetal liver cells into hepatic-like cells without fusion.
AB  - Several research groups have recently reported that certain bone marrow cells
      (BMCs) differentiate into hepatocytes in vitro as well as in vivo in rodents.
      However, it has yet to be elucidated what factors effectively trigger and sustain
      transdifferentiation of BMCs. In the present study, we specifically asked whether
      the presence of murine fetal liver cells (FLCs) triggered and supported in vitro
      transdifferentiation of murine BMCs. Fractionated BMCs from green fluorescence
      protein (GFP)-expressing transgenic mice and FLCs from ROSA26 mice (X-gal(+)
      FLCs) were cocultured in the presence of hepatocyte growth factor in laminin
      coated dishes. We found that Sca-1(+) BMCs gave rise to adherent hepatic-like
      cells, which expressed albumin as assessed with immunocytochemistry and RNA
      polymerase chain reaction (PCR), and alpha-fetoprotein and cytokeratin 19 as
      examined with RNA-PCR. When GFP(+)Sca-1(+)cKit(-) cells were cocultured with X
      gal(+) FLCs, all GFP(+) albumin-producing cells were negative for X-gal, showing
      that cell fusion was not associated in the observed BMCs' differentiation into
      hepatic-like cells. Titration analysis revealed that 1 of 5,943 Sca-1(+)cKit(-)
      cells had the ability to proliferate and differentiate into hepatic-like cells.
      These data strongly suggest that BMCs differentiate into hepatic-like cells in
      the presence of FLCs and that the present method may be useful for propagating
      BMC-derived hepatocytic progenitors and for investigating the nature of those
      cells.

PMID- 16413397
TI  - Evidence that donor intrinsic response to G-CSF is the best predictor of acute
      graft-vs-host disease following allogeneic peripheral blood stem cell
      transplantation.
AB  - OBJECTIVE: Risk factors of acute graft-vs-host disease (GVHD) following
      allogeneic bone marrow transplantation have been well described before. In this
      study, we tested the hypothesis that acute GVHD after allogeneic peripheral blood
      stem cell (PBSC) transplant might be associated with donors' responsiveness to
      granulocyte colony-stimulating factor (G-CSF), rather than the dose of CD34(+)
      cells infused. PATIENTS AND METHODS: We retrospectively analyzed mobilization and
      transplant data (demographic characteristics, donor blood cell subsets after G
      CSF, graft composition) in 149 consecutive HLA-identical donor/recipient pairs in
      order to identify acute GVHD risk factors. RESULTS: In 25% of donors, G-CSF
      mobilization led to an outstanding response, defined as greater than 117 x 10(6)
      CD34(+) cells/L. Overall, incidence of grades II-IV acute GVHD was 20.1% (95% CI:
      16.6-23.6). Following univariate analysis, the incidence increased significantly
      in recipients receiving greater than 10 x 10(6) CD34(+) cells/kg (35% vs 15%; p =
      0.007), and those transplanted from outstanding mobilizers (41% vs 12%, p <
      0.0001). In multivariate analysis, only transplantation from outstanding
      mobilizers remained significant (p = 0.02). Donor or recipient demographic
      characteristics and lymphocyte subsets reinfused in the graft had no impact.
      CONCLUSIONS: We demonstrate for the first time that donor responsiveness to G-CSF
      is associated with acute GVHD following PBSC transplantation. If confirmed, this
      correlation will help to identify recipients who could potentially benefit from
      improved prophylaxis. As further corollary, decreasing the dose of CD34(+) cells
      infused is unlikely to prevent acute GVHD. Future studies should focus on the
      molecular bases of interindividual discrepancies in response to G-CSF.

PMID- 16413398
TI  - Myeloablative and immunosuppressive properties of treosulfan in mice.
AB  - OBJECTIVE: Treosulfan is a prodrug with a specific clinical activity in ovarian
      carcinoma and other solid tumors. Due to its myeloablative and immunosuppressive
      effects, its use in conditioning regimens prior to allogeneic stem cell treatment
      (SCT) has been proposed. In the present preclinical study, myeloablative as well
      as immunosuppressive properties of treosulfan were compared with those of
      busulfan and cyclophosphamide. METHODS: Three groups of BALB/c mice were treated
      with treosulfan, cyclophosphamide, or busulfan at sublethal doses that maintained
      survival without bone marrow support. The control group was left untreated. At
      different intervals, colony-forming unit granulocyte macrophage assay was
      performed on marrow cells. Additionally, immunological analyses were performed
      using spleen cells. RESULTS: We found that treosulfan and busulfan induced a high
      and persisting degree of myeloablation, as compared with cyclophosphamide.
      Moreover, treosulfan was more effective in depletion of splenic B and T cells in
      comparison with busulfan and cyclophosphamide. Furthermore, T cells isolated from
      the spleens of treosulfan- or busulfan-treated mice were not responsive to
      allogeneic cells compared with that observed in controls and cyclophosphamide
      treated mice. Treatment with treosulfan induced only interleukin-2 production in
      spleen cells for a short time and had no significant effect on synthesis of tumor
      necrosis factor-alpha and/or interferon-gamma as compared with that observed in
      splenic T cells isolated from mice treated with either busulfan or
      cyclophosphamide. CONCLUSION: Our findings suggest that treosulfan possesses both
      myeloablative and immunosuppressive properties and may be used as a single agent
      for conditioning prior to bone marrow transplantation.

PMID- 16413399
TI  - Pressure garments for use in the treatment of hypertrophic scars--a review of the
      problems associated with their use.
AB  - Pressure garments have been the mainstay of hypertrophic scar treatment since the
      1970s. However, there are many problems associated with their use. This is the
      first in a series of papers on pressure garments that will review the literature
      published to date on the origins of pressure garments for hypertrophic scar
      treatment and the problems associated with current pressure garment use.

PMID- 16413400
TI  - Oxidative stress and diabetic cardiovascular complications.
AB  - Diabetes diagnoses are increasing at an alarming rate worldwide. The majority of
      diabetes-related deaths arise from cardiovascular complications such as
      myocardial infarction, stroke, and peripheral vascular disease. Oxidative stress
      has been demonstrated to be present in animal models as well as in patients with
      diabetes and has been suggested as a possible contributor to the accelerated
      atherosclerosis seen in diabetics. The generation of reactive oxygen species in
      diabetes occurs via several mechanisms and is initiated not only by glucose, but
      also by other substances that are found at elevated levels in diabetic patients.
      The resulting oxidative stress leads to a number of proatherogenic events. The
      elucidation of the mechanisms of oxidative stress in diabetes and their
      relationship with atherosclerosis could potentially identify molecular targets of
      therapy for this condition and its cardiovascular consequences.

PMID- 16413401
TI  - The iron-containing superoxide dismutases of trypanosomatidae.

PMID- 16413402
TI  - Commentary on "Acidosis affects tumor cell survival through modulation of nitric
      oxide release" by L. Harhaji et al.

PMID- 16413403
TI  - Functional characterisation of the iron superoxide dismutase gene repertoire in
      Trypanosoma brucei.
AB  - Superoxide dismutases (SOD) are a family of antioxidant enzymes that function by
      removing superoxide anions from the cellular environment. Here, we show that the
      African trypanosome, Trypanosoma brucei, expresses four SOD isoforms, three of
      which we have validated biochemically as iron dependent, a feature normally
      associated with prokaryotic SODs. Localisation studies reveal that two of the
      enzymes are found predominantly in a parasite-specific organelle, the glycosome
      (TbSODB1 and TbSODB2), while the other two are targeted to the mitochondrion
      (TbSODA and TbSODC). Functional analysis of the SOD repertoire in bloodstream
      form parasites was performed using an inducible RNA interference (RNAi) approach.
      Down-regulation of the glycosomal SOD transcripts corresponded with a significant
      reduction in the corresponding proteins and a dramatic level of cell death within
      the population. The importance of one of the mitochondrial enzymes (TbSODA) only
      became apparent when parasites were exposed to the superoxide-generating agent
      paraquat following induction of RNAi. These experiments therefore identify
      essential components of the superoxide metabolising arm of the T. brucei
      oxidative defence system and validate these enzymes as parasite-specific targets
      for drug design.

PMID- 16413404
TI  - The presence of four iron-containing superoxide dismutase isozymes in
      trypanosomatidae: characterization, subcellular localization, and phylogenetic
      origin in Trypanosoma brucei.
AB  - Metalloenzymes such as the superoxide dismutases (SODs) form part of a defense
      mechanism that helps protect obligate and facultative aerobic organisms from
      oxygen toxicity and damage. Here, we report the presence in the trypanosomatid
      genomes of four SOD genes: soda, sodb1, sodb2, and a newly identified sodc. All
      four genes of Trypanosoma brucei have been cloned (Tbsods), sequenced, and
      overexpressed in Escherichia coli and shown to encode active dimeric FeSOD
      isozymes. Homology modeling of the structures of all four enzymes using available
      X-ray crystal structures of homologs showed that the four TbSOD structures were
      nearly identical. Subcellular localization using GFP-fusion proteins in procyclic
      insect trypomastigotes shows that TbSODB1 is mainly cytosolic, with a minor
      glycosomal component, TbSODB2 is mainly glycosomal with some activity in the
      cytosol, and TbSODA and TbSODC are both mitochondrial isozymes. Phylogenetic
      studies of all available trypanosomatid SODs and 106 dimeric FeSODs and closely
      related cambialistic dimeric SOD sequences suggest that the trypanosomatid SODs
      have all been acquired by more than one event of horizontal gene transfer,
      followed by events of gene duplication.

PMID- 16413405
TI  - Acidosis affects tumor cell survival through modulation of nitric oxide release.
AB  - The influence of environmental pH on the production of tumoricidal free radical
      nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6
      cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release
      and subsequent reduction of cell viability in tumor cell lines. Acidification of
      cell culture medium reduced tumor cell NO production in a pH-dependent manner.
      While the inhibitory effect of acidosis on NO production in C6 cells was
      associated with a further decrease in cell viability, it completely rescued L929
      cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN
      gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein,
      and abolished the activation of iNOS transcription factor IRF-1 in L929 cells.
      Moreover, extracellular acidosis significantly impaired cytokine-induced
      phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of
      transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8)
      augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS
      activation/NO release and NO-dependent anticancer activity of rat and mouse
      macrophages. Taken together, our findings indicate that modulation of macrophage
      and tumor cell iNOS by an acidic microenvironment might influence the progression
      of NO-sensitive solid tumors.

PMID- 16413406
TI  - NADPH oxidase is involved in angiotensin II-induced apoptosis in H9C2 cardiac
      muscle cells: effects of apocynin.
AB  - Angiotensin II stimulates NADPH oxidase activity in vascular cells. However, it
      is not fully understood whether angiotensin II, which plays an important role in
      heart failure, stimulates NADPH oxidase activation and expression in cardiac
      myocytes. Previous studies have shown that angiotensin II induces myocyte
      apoptosis, but whether the change is mediated via NADPH oxidase remains to be
      elucidated. In this study we proposed to determine whether angiotensin II
      stimulated NADPH oxidase activation and NADPH oxidase subunit p47-phox expression
      in H9C2 cardiac muscle cells. If so, we would determine whether the NADPH oxidase
      inhibitor apocynin prevented angiotensin II-induced apoptosis. The results showed
      that angiotensin II increased NADPH oxidase activity, p47-phox protein and mRNA
      expression, intracellular reactive oxygen species, and apoptosis in H9C2 cells.
      Angiotensin II elevated p38 mitogen-activated protein kinase (MAPK) activity,
      decreased Bcl-2 protein, and increased Bax protein and caspase-3 activity.
      Apocynin treatment inhibited angiotensin II-induced NADPH oxidase activation and
      increases in p47-phox expression, intracellular reactive oxygen species, and
      apoptosis. The effect of apocynin on apoptosis was associated with reduced p38
      MAPK activity, increased Bcl-2 protein, and decreased Bax protein and caspase-3
      activity. These results suggest that angiotensin II-induced apoptosis is mediated
      via NADPH oxidase activation probably through p38 MAPK activation, a decrease in
      Bcl-2 protein, and caspase activation.

PMID- 16413407
TI  - S-phase arrest by reactive nitrogen species is bypassed by okadaic acid, an
      inhibitor of protein phosphatases PP1/PP2A.
AB  - In mammalian cells DNA damage activates a checkpoint that halts progression
      through S phase. To determine the ability of nitrating agents to induce S-phase
      arrest, mouse C10 cells synchronized in S phase were treated with nitrogen
      dioxide (NO(2)) or SIN-1, a generator of reactive nitrogen species (RNS). SIN-1
      or NO(2) induced S-phase arrest in a dose- and time-dependent manner. As for the
      positive controls adozelesin and cisplatin, arrest was accompanied by
      phosphorylation of ATM kinase; dephosphorylation of pRB; decreases in RF-C,
      cyclin D1, Cdc25A, and Cdc6; and increases in p21. Comet assays indicated that
      RNS induce minimal DNA damage. Moreover, in a cell-free replication system,
      nuclei from cells treated with RNS were able to support control levels of DNA
      synthesis when incubated in cytosolic extracts from untreated cells, whereas
      nuclei from cells treated with cisplatin were not. Induction of phosphatase
      activity may represent one mechanism of RNS-induced arrest, for the PP1/PP2A
      phosphatase inhibitor okadaic acid inhibited dephosphorylation of pRB; prevented
      decreases in the levels of RF-C, cyclin D1, Cdc6, and Cdc25A; and bypassed arrest
      by SIN-1 or NO(2), but not cisplatin or adozelesin. Our studies suggest that RNS
      may induce S-phase arrest through mechanisms that differ from those elicited by
      classical DNA-damaging agents.

PMID- 16413409
TI  - Specific protein interaction of human Pag with Omi/HtrA2 and the activation of
      the protease activity of Omi/HtrA2.
AB  - The human PAG gene product (hPag), one member of the TSA/AhpC family, is
      overexpressed by oxidative stress, which causes apoptosis. To investigate the
      apoptotic signal transduction mediated by hPag, hPag-binding protein was screened
      using the yeast two-hybrid system. Omi/HtrA2 was identified as the hPag-binding
      protein. Omi/HtrA2, a potent proapoptotic factor, is released from the
      mitochondria into the cytoplasm as the mature form showing serine protease
      activity during apoptosis in response to oxidative stress. We found that hPag was
      able to interact with the mature form of Omi/HtrA2, not with the precursor form
      of Omi/HtrA2. The binding of Omi/HtrA2 to hPag was shown to involve the PDZ
      binding domain in Omi/HtrA2. Also, the carboxyl-terminal domain of hPag was shown
      to be critical for the protein interaction. Using the yeast two-hybrid system and
      in vitro binding assay, the reduced form of hPag was able to interact with
      Omi/HtrA2. Interestingly, the protease activity given by the mature form of
      Omi/HtrA2 was significantly activated by the binding to hPag. Taken together,
      these results suggest that the specific protein interaction may participate as a
      molecular switch in modulating cell death in response to oxidative stress.

PMID- 16413408
TI  - Transcriptional regulation of the NADPH oxidase isoform, Nox1, in colon
      epithelial cells: role of GATA-binding factor(s).
AB  - Nonphagocytic NADPH oxidases (Noxs) are major sources of reactive oxygen species
      (ROS) and exist as a family of isoenzymes with tissue-restricted expression and
      functions. Nox1, expressed in colon epithelium and vascular smooth muscle, is
      suggested to be involved in innate immune defense and cell growth or
      proliferation. The transcriptional regulation of Nox1 appears to be particularly
      important in the modulation of its activity but the underlying mechanisms are
      unknown. Here we have identified the functional Nox1 promoter in human colon
      epithelial Caco-2 cells, and show that a 520-bp genomic fragment encompassing the
      CAP site is sufficient to direct high levels of expression of a linked reporter
      gene in these cells. Deletion analyses together with electrophoretic mobility
      shift assays (EMSAs) suggest that maximal promoter activity is dependent on a
      GATA-binding site, conserved between human and mouse, within the proximal
      promoter region. The ability of mouse GATA factors to transactivate the Nox1
      promoter was demonstrated in Cos-7 cells and site-directed mutagenesis of the
      conserved GATA-binding site further demonstrates that the regulation of Nox1
      transcription is mediated by the direct binding of a GATA factor to the Nox1
      proximal promoter. We also identified more distal, upstream regions which act to
      repress significantly expression from the Nox1 promoter.

PMID- 16413410
TI  - Blocking tumor cell eicosanoid synthesis by GP x 4 impedes tumor growth and
      malignancy.
AB  - Using tumor cell-restricted overexpression of glutathione peroxidase 4 (GP x 4),
      we investigated the contribution of tumor cell eicosanoids to solid tumor growth
      and malignant progression in two tumor models differing in tumorigenic potential.
      By lowering cellular lipid hydroperoxide levels, GP x 4 inhibits cyclooxygenase
      (COX) and lipoxygenase (LOX) activities. GP x 4 overexpression drastically
      impeded solid tumor growth of weakly tumorigenic L929 fibrosarcoma cells, whereas
      B16BL6 melanoma solid tumor growth was unaffected. Yet, GP x 4 overexpression did
      markedly increase the sensitivity of B16BL6 tumors to angio-destructive TNF-alpha
      therapy and abolished the metastatic lung colonizing capacity of B16BL6 cells.
      Furthermore, the GP x 4-mediated suppression of tumor cell prostaglandin E(2)
      (PGE(2)) production impeded the induction of COX-2 expression by the tumor stress
      conditions hypoxia and inflammation. Thus, our results reflect a PGE(2)-driven
      positive feedback loop for COX-2 expression in tumor cells. This was further
      supported by the restoration of COX-2 induction capacity of GP x 4-overexpressing
      L929 tumor cells when cultured in the presence of exogenous PGE(2). Thus,
      although COX-2 expression and eicosanoid production may be enabled by PGE(2) from
      the tumor microenvironment, our results demonstrate the predominant tumor cell
      origin of protumoral eicosanoids, promoting solid tumor growth of weakly
      tumorigenic tumors and malignant progression of strongly tumorigenic tumors.

PMID- 16413411
TI  - Plasma nitrite concentrations reflect the degree of endothelial dysfunction in
      humans.
AB  - A reduced nitric oxide availability is a hallmark of endothelial dysfunction
      occurring early in atherosclerosis. Recently, we have shown that plasma nitrite
      mirrors acute changes in endothelial nitric oxide synthase activity in various
      mammals, including humans. Here, we examined the hypothesis that plasma nitrite
      levels are reduced in humans with endothelial dysfunction and the decrease is
      correlated with increasing numbers of cardiovascular risk factors (RF). Plasma
      nitrite concentrations were quantified by flow-injection analysis. The
      coefficient of variation for repeated measurements of plasma nitrite was <8%, and
      heart rate and blood pressure at the time of blood sampling had no significant
      effect on nitrite values measured (n=10). Baseline levels of plasma nitrite
      followed a normal distribution in each group studied and decreased progressively
      with increasing numbers of cardiovascular risk factors (n=351, p<0.001): 351+/-13
      (0 RF), 261+/-10 (1 RF), 253+/-11 (2 RF), 222+/-18 (3 RF), and 171+/-29 nmol/L (4
      RF). Intima media thickness (IMT) and flow-mediated dilation (FMD) were
      determined via ultrasound. Plasma nitrite and FMD levels were lower, whereas IMT
      was greater in individuals with endothelial dysfunction (n=12) compared to
      healthy volunteers (n=12). Nitrite correlated significantly with FMD (r=0.56,
      p<0.001) and inversely with IMT (r= -0.49, p<0.01). Plasma nitrite levels are
      reliably measurable in humans, indicate endothelial dysfunction, and correlate
      with cardiovascular risk factors. Future studies are necessary to identify the
      prognostic relevance of plasma nitrite determination in patients suffering from
      cardiovascular disease.

PMID- 16413412
TI  - Uncoupling protein 1 affects the yeast mitoproteome and oxygen free radical
      production.
AB  - Uncoupling protein 1 (UCP1) is a mitochondrial inner membrane protein that
      dissipates the proton electrochemical gradient built up by the respiratory chain.
      Its activity is stimulated by free fatty acids and inhibited by purine
      nucleotides. Here we investigated how active and regulated recombinant UCP1
      expressed in yeast at approximately 1 and approximately 10 microg/mg of total
      mitochondrial proteins induced changes in the mitochondrial proteome and in
      oxygen free radical production. Using two-dimensional differential in-gel
      electrophoresis (2D-DIGE), we found that most of the proteins involved in the
      response to ectopically expressed UCP1 are related to energy metabolism. We also
      quantified the cellular H(2)O(2) release in the absence or in the presence of
      UCP1. Our results suggest that UCP1 has a dual influence on free radical
      generation. On one side, FFA-activated UCP1 was able to decrease the superoxide
      anion production, demonstrating that a decrease in the generation of reactive
      oxygen species is an obligatory outcome of UCP1 activity even in a heterologous
      context. On the other side, an increase in UCP1 content was concomitant with an
      increase in the basal release of superoxide anion by mitochondria as a side
      consequence of the overall increase in oxidative metabolism.

PMID- 16413413
TI  - Seizure-induced changes in mitochondrial redox status.
AB  - The aim of this study was to determine seizure-induced oxidative stress by
      measuring hippocampal glutathione (GSH) and glutathione disulfide (GSSG) levels
      in tissue and mitochondria. Kainate-induced status epilepticus (SE) in rats
      resulted in a time-dependent decrease of GSH/GSSG ratios in both hippocampal
      tissue and mitochondria. However, changes in GSH/GSSG ratios were more dramatic
      in the mitochondrial fractions compared to hippocampal tissue. This was
      accompanied by a mild increase in glutathione peroxidase activity and a decrease
      in glutathione reductase activity in hippocampal tissue and mitochondria,
      respectively. Since coenzyme A (CoASH) and its disulfide with GSH (CoASSG) are
      primarily compartmentalized within mitochondria, their measurement in tissue was
      undertaken to overcome problems associated with GSH/GSSG measurement following
      subcellular fractionation. Hippocampal tissue CoASH/CoASSG ratios were decreased
      following kainate-induced SE, the time course and magnitude of change paralleling
      mitochondrial GSH/GSSG levels. Cysteine, a rate-limiting precursor of glutathione
      was decreased following kainate administration in both hippocampal tissue and
      mitochondrial fractions. Together these changes in altered redox status provide
      further evidence for seizure-induced mitochondrial oxidative stress.

PMID- 16413415
TI  - Catalase enrichment using recombinant adenovirus protects alphaTN4-1 cells from
      H(2)O(2).
AB  - Since oxidative stress has been implicated in the development of numerous
      diseases including cataract, this laboratory has created and investigated the
      stress response of murine immortal lens epithelial cell lines (alphaTN4-1)
      conditioned to withstand lethal peroxide concentrations. Two of a group of
      antioxidative defense (AOD) enzymes found in such cells to have markedly enhanced
      activity are catalase (CAT) and GSH S-transferase alpha2 (GST). In order to
      determine if enrichment of one or both of these AODs is sufficient to protect
      alphaTN4-1 cells from lethal H(2)O(2) levels, these cells were infected with
      adenovirus vectors capable of expressing these AODs at a high level. With this
      system, gene enrichment and increased enzyme activity were observed with both CAT
      and GST vectors. The percentage of cells infected ranged from about 50 to 90%
      depending on the multiplicity of infection (MOI). CAT but not GST protected the
      cells from H(2)O(2) stress. The CAT activity was increased from 15- to 150-fold
      and even at the lower levels protected the cells from H(2)O(2) concentrations as
      high as 200 microM or more (H(2)O(2) levels which rapidly kill non-enriched
      cells). Even when only about 50% of the cell population is infected as judged by
      GFP infection, the entire population appeared to be protected based on cell
      viability. The CAT enrichment appears to protect other intracellular defense
      systems such as GSH from being depleted in contrast to non-enriched cell
      populations where GSH is rapidly exhausted. The overall results suggest that
      enriching the cellular CAT gene level with an appropriate recombinant viral
      vector may be sufficient to protect in vivo systems from peroxide stress.

PMID- 16413414
TI  - The reaction of flavanols with nitrous acid protects against N-nitrosamine
      formation and leads to the formation of nitroso derivatives which inhibit cancer
      cell growth.
AB  - Studies have suggested that diets rich in polyphenols such as flavonoids may lead
      to a reduced risk of gastrointestinal cancers. We demonstrate the ability of
      monomeric and dimeric flavanols to scavenge reactive nitrogen species derived
      from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited
      nitrous acid-induced formation of 3-nitrotyrosine and the formation of the
      carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and
      dimeric epicatechin with nitrous acid led to the formation of mono- and di
      nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the
      formation of nitrated products. Although, epicatechin was transferred across the
      jejunum of the small intestine yielding metabolites, its nitroso form was not
      absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of,
      and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3
      activation and reductions in Akt phosphorylation, suggesting activation of
      apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso
      derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also
      induced significant toxic effects in Caco-2 cells. The inhibitory effects on
      cellular proliferation were paralleled by early inhibition of ERK 1/2
      phosphorylation and later reductions in cyclin D1 levels, indicating modulation
      of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes
      in which dietary derived flavanols may exert beneficial effects in the
      gastrointestinal tract.

PMID- 16413416
TI  - The induction of human superoxide dismutase and catalase in vivo: a fundamentally
      new approach to antioxidant therapy.
AB  - A composition consisting of extracts of five widely studied medicinal plants
      (Protandim) was administered to healthy human subjects ranging in age from 20 to
      78 years. Individual ingredients were selected on the basis of published findings
      of induction of superoxide dismutase (SOD) and/or catalase in rodents in vivo,
      combined with evidence of decreasing lipid peroxidation. Each ingredient was
      present at a dosage sufficiently low to avoid any accompanying unwanted
      pharmacological effects. Blood was analyzed before supplementation and after 30
      and 120 days of supplementation (675 mg/day). Erythrocytes were assayed for SOD
      and catalase, and plasma was assayed for lipid peroxidation products as
      thiobarbituric acid-reacting substances (TBARS), as well as uric acid, C-reactive
      protein, and cholesterol (total, LDL, and HDL). Before supplementation, TBARS
      showed a strong age-dependent increase. After 30 days of supplementation, TBARS
      declined by an average of 40% (p = 0.0001) and the age-dependent increase was
      eliminated. By 120 days, erythrocyte SOD increased by 30% (p < 0.01) and catalase
      by 54% (p < 0.002). We conclude that modest induction of the catalytic
      antioxidants SOD and catalase may be a much more effective approach than
      supplementation with antioxidants (such as vitamins C and E) that can, at best,
      stoichiometrically scavenge a very small fraction of total oxidant production.

PMID- 16413417
TI  - Activation of a novel isoform of methionine adenosyl transferase 2A and increased
      S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia.
AB  - S-Adenosylmethionine (SAM, AdoMet) is the most important methyl donor used for
      synthesis of nucleic acids, phospholipids, creatine, and polyamines and for
      methylation of many bioactive molecules. The metabolic response of the lung to
      oxidative stress of hyperoxia requires increased RNA and protein synthesis for
      energy metabolism, growth arrest, and antioxidant defense. We studied the
      production of SAM and other aspects of methionine metabolism in lung epithelial
      cells exposed to hyperoxia. Human lung epithelial-like (A549) and primary small
      airway epithelial (SAE) cells were exposed to normoxia (21% O(2)) or hyperoxia
      (95% O(2)). Cell methionine and S-adenosylmethionine content increased in
      response to hyperoxia in SAE and A549 cells. Because methionine adenosyl
      transferase (MAT) is the rate-limiting enzyme of the pathway, we examined the
      expression of a lung epithelial isoform of MAT 2A in hyperoxia. Western blots
      revealed a novel MAT 2A isoform expressed in both cell types, with a lower
      molecular mass than that described in Jurkat cells. Cloning and sequencing of the
      MAT 2A cDNA revealed one silent nucleotide substitution compared to that
      expressed in Jurkat. The lower mass of MAT 2A in both lung epithelial cells
      indicated that the absence of the major posttranslational modification of MAT 2A
      found in Jurkat. MAT 2A protein progressively increased during hyperoxic exposure
      in both transformed and primary lung epithelium. Increased flux of (13)C-labeled
      methionine to S-adenosylhomocysteine (SAH) in A549 demonstrated that SAM's methyl
      group was utilized, and increased formation of cystathionine indicated that at
      least part of SAM generated was directed toward cysteine/GSH in the
      transsulfuration pathway. These results indicate activation of MAT 2A and the
      transmethylation pathway in the metabolic response to hyperoxia in lung
      epithelium.

PMID- 16413420
TI  - We are here to help.

PMID- 16413418
TI  - Acetylcarnitine and cellular stress response: roles in nutritional redox
      homeostasis and regulation of longevity genes.
AB  - Aging is associated with a reduced ability to cope with physiological challenges.
      Although the mechanisms underlying age-related alterations in stress tolerance
      are not well defined, many studies support the validity of the oxidative stress
      hypothesis, which suggests that lowered functional capacity in aged organisms is
      the result of an increased generation of reactive oxygen and nitrogen species.
      Increased production of oxidants in vivo can cause damage to intracellular
      macromolecules, which can translate into oxidative injury, impaired function and
      cell death in vulnerable tissues such as the brain. To survive different types of
      injuries, brain cells have evolved networks of responses, which detect and
      control diverse forms of stress. This is accomplished by a complex network of the
      so-called longevity assurance processes, which are composed of several genes
      termed vitagenes. Among these, heat shock proteins form a highly conserved system
      responsible for the preservation and repair of the correct protein conformation.
      The heat shock response contributes to establishing a cytoprotective state in a
      wide variety of human diseases, including inflammation, cancer, aging and
      neurodegenerative disorders. Given the broad cytoprotective properties of the
      heat shock response, there is now a strong interest in discovering and developing
      pharmacological agents capable of inducing the heat shock response.
      Acetylcarnitine is proposed as a therapeutic agent for several neurodegenerative
      disorders, and there is now evidence that it may play a critical role as
      modulator of cellular stress response in health and disease states. In the
      present review, we first discuss the role of nutrition in carnitine metabolism,
      followed by a discussion of carnitine and acetyl-l-carnitine in mitochondrial
      dysfunction, in aging, and in age-related disorders. We then review the evidence
      for the role of acetylcarnitine in modulating redox-dependent mechanisms leading
      to up-regulation of vitagenes in brain, and we also discuss new approaches for
      investigating the mechanisms of lifetime survival and longevity.

PMID- 16413422
TI  - Western Nebraska flight program celebrates a decade of service.

PMID- 16413421
TI  - Motor vehicle crash with multiple injuries.

PMID- 16413423
TI  - Medical helicopters in wilderness search and rescue operations.
AB  - Medical helicopters may be asked to assist in wilderness search and rescue (SAR)
      operations to quickly reach patients in remote areas and provide medical care and
      transport of sick or injured persons. The number 1 priority for any medical
      helicopter involved in an SAR operation is safety, which is considered at each
      decision point. The involvement of a medical helicopter service begins with a
      request from a local agency for support. Obtaining key information about the SAR
      operation from the local agency is essential for deciding whether to accept the
      mission and for making appropriate preparations for the mission. While en route
      to the SAR location, the medical crew can review the information regarding
      location and patient status. Once on location, the crew can survey the scene from
      the air before landing at the command post to brief with SAR personnel regarding
      the mission. An initial survey of the scene from the air is important for
      identifying landing zones and evaluating the terrain where the rescue will occur.
      A face-to-face briefing with SAR personnel is preferable to learn specifically
      what type of mission is requested. The medical helicopter crew is empowered to
      decline the mission for safety reasons at any step. The actual rescue may be done
      by inserting the helicopter at the scene in nontechnical terrain or by having SAR
      personnel extricate the patient and deliver him or her to the medical helicopter
      crew at the nearest safe landing zone. Medical care and transport of the patient
      as indicated by injuries or illness then occurs. Finally, a postmission
      debriefing is essential for identifying problems that occurred during the mission
      and implementing corrections for improvement.

PMID- 16413424
TI  - Transport of winter resort injuries to regional trauma centers.
AB  - INTRODUCTION: This study examined the epidemiology of winter resort injuries
      presenting to regional trauma centers by helicopter (HEMS) or ground (GEMS)
      ambulance. METHODS: Five hundred seventy-five patients (GEMS 289; HEMS 286) were
      identified from trauma registries and HEMS transport records. Demographic data,
      hospital interventions, and discharge status were examined. RESULTS: HEMS
      patients had a significantly lower Glasgow coma score (GCS) and trauma score
      (TS), longer intensive care unit (ICU) length of stay (LOS), and more deaths than
      did GEMS patients (P < 0.05). Despite this, significantly more HEMS patients were
      discharged home from the emergency department (24.5% vs. 4.8%; P < 0.001). HEMS
      patients had more isolated head/facial injuries and multiple injuries, with less
      isolated extremity injuries than did GEMS patients (P < 0.05). Regardless of
      transport mode, patients with multiple injuries, thoracoabdominal injuries, or
      head injuries with a GCS < or = 13 were more likely to require immediate
      interventions (intubation, chest tube, blood products). Patients with isolated
      extremity injuries rarely needed immediate care. CONCLUSION: HEMS patients had a
      higher acuity and different injury pattern when compared to GEMS patients.
      Approximately 24.5% of HEMS patients were discharged home from the ED. This
      reflects significant overtriage of patients to HEMS. A prospective study
      examining the initial triage of patients injured at winter resorts would help to
      determine which subset of patients are best served by HEMS transport.

PMID- 16413425
TI  - Oxygen conservation during long-distance transport of ventilated patients:
      assessing the Modified Circle System.
AB  - INTRODUCTION: The Modified Circle System was developed to reduce the amount of
      oxygen required for long-distance transportation of ventilated patients. Formal
      testing of the system has never been documented. Various aspects of the system
      were tested, with the study broken into four parts. METHODS: Bench testing was
      performed with a test lung that simulated two different lung compliances. Four
      ventilators were tested with the system. The four parts to the study were oxygen
      flow rates, position of oxygen inflow, pressure drop across the system, and
      specific testing with the LP 10 ventilator. RESULTS: The minimum oxygen flows
      required to maintain forced inspiratory oxygen (FiO(2)) higher than 0.93 over a
      range of ventilator and lung settings was 1.5 L/min. The oxygen inflow is best
      connected directly to the CO(2) absorber unit. A significant pressure drop occurs
      across the system, which increases progressively with higher ventilator
      pressures. The LP 10 does not allow improved oxygen conservation when recycling
      gases via its air inlet port. CONCLUSION: The study provides previously unknown,
      clinically important information regarding the performance of the Modified Circle
      System.

PMID- 16413426
TI  - Unusual placement of an endotracheal tube in a patient with blunt traumatic
      airway injuries.

PMID- 16413427
TI  - Diagnosis of chronic pain caused by osteoarthritis and prescription of analgesics
      in patients with cognitive impairment.
AB  - OBJECTIVE: Evaluation of the ability to detect symptoms of osteoarthritis and
      prescription of analgesics in older adults with different degrees of cognitive
      impairment. SETTING AND PATIENTS: Patients consecutively admitted to a Geriatric
      Evaluation and Rehabilitation Unit (GERU) for disability due to orthopedic,
      neurological, or cardiopulmonary diseases, after a surgical intervention, or for
      behavioral disturbances of dementia. Subjects with a recent orthopedic
      intervention were excluded. Eight hundred eighty-eight patients were analyzed
      (mean age 78.4 +/- 7.2 years, 69.5% female) and divided into 4 groups according
      to cognitive impairment: severe (Mini-Mental State Examination, MMSE 0-12),
      moderate (MMSE 13-18), mild (MMSE 19-24), or absent (MMSE 25-30). METHODS:
      Patients underwent a geriatric multidimensional assessment; the diagnosis of
      musculoskeletal pain was based on patients' direct report, objective signs
      (inflammatory signs around the joints), and "pain behaviors" (reductions in
      activity, social withdrawal, self-protective maneuvers, increased alterations in
      facial expressions or body postures, observable displays of distress). Analgesic
      drugs were registered on discharge in subjects with symptomatic osteoarthritis.
      RESULTS: Of the patients admitted to GERU, 16.8% (n = 149) had osteoarthritis;
      this percentage is different according to cognitive impairment (MMSE 0-12: 1%,
      MMSE 13-18: 8%, MMSE 19-24: 17.4%, MMSE 24-30: 34.1%, P < .001). If patients
      admitted for osteoarthritis are excluded, the new diagnoses of pain due to
      osteoarthritis are 306 (41.4%), without differences between cognitive status
      groups. On discharge, analgesic drugs are prescribed to 28.8% of patients with
      symptomatic arthritis (n = 131); the percentage is lower in patients with severe
      cognitive impairment in comparison with subjects with better cognitive functions.
      CONCLUSION: There is a poor attention to chronic pain due to osteoarthritis in
      community-dwelling elders with cognitive impairment. In a rehabilitative setting,
      an accurate evaluation of objective signs allows the diagnosis of symptomatic
      osteoarthritis. However, the link between the diagnosis and the treatment is not
      direct, since the prescription of analgesics is lower in patients with a more
      severe cognitive impairment.

PMID- 16413428
TI  - Oral ddAVP for nighttime urinary incontinence in characterized nursing home
      residents: a pilot study.
AB  - OBJECTIVES: To (1) identify abnormalities in arginine vasopressin (AVP, a water
      conserving hormone) secretion and release in nursing home (NH) residents with
      nighttime urinary incontinence (UI); and (2) perform a pilot test of desmopressin
      acetate (ddAVP, a synthetic analog of the naturally occurring hormone)
      replacement in these residents. DESIGN: Diagnostic evaluation and open-label
      treatment trial. SETTING: Two community nursing homes in a metropolitan area.
      PARTICIPANTS: Male and female NH residents 65 years of age and older with
      nighttime UI. INTERVENTION: Characterizations of AVP status followed by a 7-day
      open-label trial of oral ddAVP (either 0.1 mg or 0.2 mg). MEASUREMENTS: Water
      deprivation test results, AVP levels, voided volumes, number of voids,
      incontinent episodes, number of nighttime checks found wet (out of 6 total checks
      per night). RESULTS: All participants had measurable AVP levels of 2.0 pg/mL or
      higher. Six of 10 individuals had an abnormal water deprivation test. Two of 4
      participants on 0.2 mg of ddAVP and 2 of 6 participants on 0.1 mg had a 200 mL or
      more mean reduction in nighttime urine volume. Both ddAVP dosages yielded a mean
      reduction of 0.7 fewer nighttime wet checks found wet. One participant in each
      group developed hyponatremia (1 of 6 on 0.1 mg and 1 of 4 on 0.2 mg).
      Hyponatremia resolved with discontinuation of the drug. CONCLUSION: Both 0.1 mg
      and 0.2 mg of ddAVP given to carefully screened NH residents for 7 days produced
      a modest average reduction in nighttime urine volume and number of nighttime
      incontinent episodes that is likely of little clinical importance. The role of
      ddAVP in this population requires further research.

PMID- 16413429
TI  - Antipsychotic drug use among nursing home residents taking rivastigmine.
AB  - OBJECTIVE: To evaluate whether or not rivastigmine use is associated with a
      decrease in the initiation of antipsychotic drug therapy among nursing home
      residents in the United States. METHODS: A retrospective analysis was performed
      using Minimum Data Set data and physician order files for newly admitted
      residents of 452 US nursing facilities from 2000 through 2002. The rivastigmine
      group included those who were diagnosed with Alzheimers disease (AD) and began
      rivastigmine treatment within 30 days of diagnosis. Patients were required to be
      on treatment for a minimum of 30 days. The control group included those who were
      diagnosed with AD, but did not receive a cholinesterase inhibitor. All subjects
      were antipsychotic drug-naive within 30 days of baseline (initiation of
      rivastigmine or initial AD diagnosis). A Cox proportional hazards model was used
      to estimate predicted risk of antipsychotic drug use. RESULTS: This study
      included 845 patients in the rivastigmine group and 517 patients in the control
      group. The rivastigmine group had fewer female patients, was younger, and had
      more verbal distress, sleep issues, sadness, loss of interest, and behavioral
      symptoms at baseline compared with the control group (P < .01). Overall
      initiation of antipsychotics was lower in the rivastigmine group (8.6%) compared
      with the control group (17.0%). Patients in the control group were almost 2 times
      more likely (relative risk = 1.86; P < .001) to take antipsychotics compared with
      patients taking rivastigmine, after adjusting for demographic covariates and
      mental health conditions or behavioral symptoms at baseline. Patients with
      baseline mental health conditions or behavioral symptoms were more likely to
      start antipsychotics than those without such conditions (P < .001). CONCLUSIONS:
      Study results suggest that nursing home residents with Alzheimers disease treated
      with rivastigmine have a reduced risk of initiating therapy with an antipsychotic
      drug compared with residents who do not receive cholinesterase inhibitor
      treatment.

PMID- 16413430
TI  - Racial and socioeconomic differences in psychiatric symptoms in nursing home
      residents: a minimum data set-based pilot study.
AB  - BACKGROUND: Little research has explored racial and socioeconomic differences in
      the presence, detection, and treatment of neuropsychiatric symptoms in nursing
      home residents. OBJECTIVE: To evaluate racial and socioeconomic differences on
      mood and behavior Minimum Data Set (MDS) recorded symptoms, MDS recorded
      psychiatric diagnoses, and MDS identified psychotropic medication use. METHODS:
      Data were obtained through a cross-sectional review of MDS data of 290 African
      American and white residents of 2 nursing homes. The association between age,
      gender, race, and pay status with mood and behavior patterns, psychiatric
      diagnoses, and use of psychotropic medication was evaluated. RESULTS: White
      residents were more likely than African American residents to have MDS recorded
      psychiatric diagnoses (odds ratio, OR = 3.24), but there were no significant
      racial differences in recorded mood or behavior symptomatology or in the
      pharmacologic treatment of mental illness. Medicaid recipients were more likely
      than nonrecipients to have behavior symptoms (OR = 2.09), have a psychiatric
      diagnosis (OR = 2.91), and receive psychotropic medications in the absence of a
      psychiatric diagnosis (OR = 3.62). CONCLUSION: Pay status was associated with
      recorded symptoms, diagnoses, and medications, but racial differences were found
      only for recorded diagnoses.

PMID- 16413431
TI  - To anticoagulate or not to anticoagulate? A common dilemma for the provider:
      physicians' opinion poll based on a case study of an older long-term care
      facility resident with dementia and atrial fibrillation.
AB  - OBJECTIVE: Anticoagulation therapy is an acceptable strategy for the prevention
      of thromboembolic events in the presence of atrial fibrillation. However, this
      strategy is controversial in older subjects particularly in the presence of
      dementia. We conducted an opinion poll regarding the decision to anticoagulate or
      not among physicians in practice and in various levels of training (residents and
      fellows) that was based on a specific, yet not unusual, case scenario in the
      nursing home. SETTING: A university teaching hospital in the Bronx, NY. METHODS:
      A survey questionnaire was distributed to physicians to solicit opinions on the
      decision to anticoagulate based on an actual case from a LTCF and the results
      were analyzed. RESULTS: One hundred seven completed surveys were returned from 49
      residents, 20 fellows, and 38 attending physicians. The majority (85%) felt that
      long-term anticoagulation therapy was not indicated in the case patient. However,
      most (88%) felt they would provide an antiplatelet agent, with the choice being
      78% aspirin, 20% clopridogel, and 2% aspirin-dipyridamole. The most cited reasons
      for not providing anticoagulation were risk of falls (98%), dementia (40%), and
      short life expectancy (32%). However, 92% of respondents felt that the patient
      was a candidate for short-term anticoagulation therapy. Interestingly, the
      choices (yes, no, uncertain) to the questions were similar for all physicians
      irrespective of their level of training or years in practice (or faculty) after
      training. CONCLUSIONS: Although long-term anticoagulation for thromboembolic
      events in atrial fibrillation is considered beneficial, recent reports suggest
      that warfarin is underused in older adults, especially in the long-term care
      setting. Our physician poll, based on a specific case scenario, is consistent
      with this opinion as reflected by both trainees and practicing physicians. While
      there are absolute and relative contraindications to the use of long-term
      warfarin, decisions should be individualized and based on risks, benefits, and
      quality of life of the resident.

PMID- 16413432
TI  - Treatment of systolic and diastolic heart failure in the elderly.
AB  - Underlying causes, risk factors, and precipitating causes of heart failure (HF)
      should be treated. Drugs known to precipitate or aggravate HF should be stopped.
      Patients with HF and an abnormal left ventricular ejection fraction (LVEF)
      (systolic heart failure) or normal LVEF (diastolic HF) should be treated with
      diuretics if fluid retention is present; with an angiotensin-converting enzyme
      (ACE) inhibitor or an angiotensin receptor blocker if the patient cannot tolerate
      an ACE inhibitor because of cough, angioneurotic edema, rash, or altered taste
      sensation; and with a beta blocker unless contraindicated. If severe systolic HF
      persists, an aldosterone antagonist should be added. If HF persists, isosorbide
      dinitrate plus hydralazine should be added. Calcium channel blockers should be
      avoided if systolic HF is present. Digoxin should be avoided in men and women
      with diastolic HF if sinus rhythm is present and in women with systolic HF.
      Digoxin should be given to men with systolic HF if symptoms persist, but the
      serum digoxin level should be maintained between 0.5 and 0.8 ng/mL. A
      multidisciplinary approach should be used with nurse monitoring of the condition.
      In a home-bound patient, a homemaker should be hired.

PMID- 16413434
TI  - Meal rounds: an essential aspect of quality nutrition services in long-term care.
AB  - INTRODUCTION AND RATIONALE: Weight change and, specifically, weight loss are
      common in residents of long-term care facilities (LTCFs). The occurrence of
      weight change results from multifactorial processes, some of which can be
      considered nutrition risk factors. Meal rounds can be a continuous quality
      improvement activity to readily identify nutrition risk factors that can
      influence weight change. METHODS: This brief report will describe the activity of
      meal rounds and how they can be used to improve nutrition services. Baseline data
      from a previously published study on 37 residents will provide proportions of
      nutrition risk factors identified during meal rounds that can influence weight
      change. OUTCOMES: Feeding and eating difficulties are prevalent in residents with
      dementia (eg, agitation 29.7%, resisting assistance 21.6%). Early identification
      of these difficulties using meal rounds may be a means of preventing weight
      change and promoting quality nutrition care in LTCFs. The proposed intervention
      of meal rounds conducted as described can improve the quality of nutrition
      services in LTCFs.

PMID- 16413433
TI  - Experience with the rapid Directigen test for influenza.
AB  - OBJECTIVE: To determine the sensitivity and positive predictive value of the
      Becton-Dickson Directigen AB performed on-site in a nursing home compared to
      viral culture. SETTING: A 721-bed skilled nursing facility for veterans and
      spouses. DESIGN MEASUREMENTS: Nasopharyngeal specimens were obtained with a low
      clinical threshold from residents during 3 influenza seasons for rapid antigen
      testing in the nursing home. The specimens were then transported for viral
      culture by courier on ice to a laboratory 45 miles away. RESULTS: A total of 327
      samples were obtained; 36 were positive for influenza A by rapid test, and all
      but 2 grew the organism on tissue culture with a positive predictive value of
      94%. Nineteen specimens were negative by rapid test, but grew influenza A on
      tissue culture with a sensitivity of 64%. Influenza prophylaxis was usually
      initiated the day the first positive rapid test was encountered when influenza
      was active in the community. CONCLUSION: The Directigen AB is a reliable
      indicator of influenza when influenza has been culture-confirmed in the
      community. Although sensitivity is limited, a group of rapid tests provided early
      laboratory confirmation and facilitated the application of prophylaxis.

PMID- 16413435
TI  - Prevention and treatment of pressure ulcers.
AB  - Pressure ulcers are complex chronic wounds for which no gold standard for
      prevention or treatment has yet been established. Several attempts at developing
      guidelines has been undertaken by different organizations. Pressure ulcers are
      devastating comorbidities for patients and difficult to prevent or manage.
      Whether or not pressure ulcers are preventable remains controversial. The
      strategy for prevention includes recognizing the risk, decreasing the effects of
      pressure, assessing nutritional status, avoiding excessive bed rest and prolonged
      sitting, and preserving the integrity of the skin. The principles of treatment of
      pressure ulcers include assessing severity, reducing pressure, friction and shear
      forces, optimizing local wound care, removing necrotic debris, managing bacterial
      contamination, and correcting nutritional deficits.

PMID- 16413436
TI  - Comments on racial and socioeconomic differences in psychiatric symptoms in
      nursing home residents.

PMID- 16413437
TI  - Continuous quality improvement for nutritional care services in nursing homes:
      the importance of direct observation.

PMID- 16413438
TI  - The next step: palliative care for advanced heart failure.

PMID- 16413439
TI  - Preventing the transmission of bloodborne viruses during glucose monitoring:
      lessons learned from recent outbreaks.

PMID- 16413440
TI  - 2005 presidential address.

PMID- 16413441
TI  - Direct current stimulation for spine fusion in a nicotine exposure model.
AB  - BACKGROUND CONTEXT: Decreased effectiveness in spinal fusion procedures in
      patients who smoke before, during, or after the operation has been noted in
      several clinical studies. In previous work, direct current (DC) electrical
      stimulation has been shown to enhance inter-transverse process fusion in a rabbit
      model. PURPOSE: To test the efficacy of DC stimulation on bone healing in spinal
      fusion in rabbits exposed to nicotine. STUDY DESIGN/SETTING: A randomized and
      controlled interventional study. METHODS: Thirty male New Zealand white rabbits
      received a single level posterolateral, inter-transverse process fusion with
      autologous iliac crest bone. One group (control) acted as a control without
      nicotine or electrical stimulation. A second group (Nic) received a continuous
      dose of nicotine via a transdermal patch to simulate a heavy smoker, and a third
      group, nicotine/stimulator group (Nic/Stim), additionally received a 100-microamp
      DC stimulator. The fusion masses (L5-L6) and the adjacent unfused control segment
      (L4-L5) were evaluated radiographically, manually, and biomechanically. RESULTS:
      The Nic group showed significantly higher fusion rate compared with the control
      group. The Nic/Stim group also demonstrated significantly higher fusion rate and
      X-ray trabeculation compared with the control group. However, the Nic/Stim group
      was not significantly higher than the Nic group in fusion rate or X-ray
      trabeculation. CONCLUSIONS: Nicotine significantly improved fusion rate compared
      with controls, and DC stimulation significantly increased X-ray trabeculation of
      nicotine treated rabbits compared with controls.

PMID- 16413442
TI  - A prospective study of Autologous Growth Factors (AGF) in lumbar interbody
      fusion.
AB  - BACKGROUND: Numerous preclinical and clinical studies have reported on the use of
      platelet concentrates to promote tissue healing. The results in spinal fusion
      applications are limited and controversial. PURPOSE: The purpose of the current
      prospective clinical cohort study is to assess the effect of Autologous Growth
      Factors (AGF) on lumbar interbody fusion with specific attention paid to
      determination of clinical and radiographic outcomes. STUDY DESIGN/SETTING:
      Prospective clinical study PATIENT SAMPLE: Candidates for anterior-posterior
      lumbar fusion with diagnosis of degenerative disc disease and/or up to grade I
      spondylolytic spondylolisthesis based on positive provocative discography.
      OUTCOME MEASURES: Clinical (visual analogue pain scale/functional outcome
      assessment) and radiographic outcomes (fusion on computed tomography at 6 months
      and plain radiographs at 12 and 24 months). METHODS: Thirty-seven patients were
      assigned to standard anterior-posterior interbody fusion L2-S1 (single or two
      level) using iliac crest bone graft (autograft group: 22 patients with 32 levels
      operated) or allograft combined with autogenous growth factors (AGF group: 15
      patients with 25 levels operated). Radiographic outcomes were collected at 6
      months postsurgery with computed tomography and at 12 and 24 months with plain
      radiographs. Pre- and postoperative clinical outcome measures included visual
      analog scores (VAS) for back and leg pain (0-10), SF-36 scores, and Oswestry
      disability determination. Average clinical and radiographic follow-up for the
      autograft group was 24.3+/-5.6 months (12-36 months) and AGF was 25.7+/-7.5 (6-40
      months). RESULTS: Fusion incorporation at each end plate was determined at 56% in
      both autograft and AGF (p=NS) patients based on computed tomography at 6 months
      with minimal subsidence noted and no direct correlation between the incidence or
      degree of cage subsidence and bone graft technique. The 12- and 24-month
      radiographic results confirmed an 85% arthrodesis rate for the autograft
      patients, whereas the AGF patients had an 89% fusion rate (p=NS). Clinical
      outcomes were similar for both groups and no significant differences were noted
      for pain or functional outcome improvements. CONCLUSIONS: AGF combined with an
      allograft carrier is equivalent in radiographic and clinical outcomes to
      autograft in one- or two-level lumbar interbody fusion with supplemental
      posterior fixation and, thus, eliminates any morbidity from iliac crest bone
      graft harvesting. AGF combined with an appropriate carrier is a reasonable
      alternative to autograft and expensive bone induction technologies. Further
      research is still required to examine the optimum carriers, preparation and
      formulation, and platelet concentrations for this technology.

PMID- 16413443
TI  - MOS short form 36 and Oswestry Disability Index outcomes in lumbar fusion: a
      multicenter experience.
AB  - BACKGROUND CONTEXT: Patient-based quality of life scales have become a critical
      element of post-op assessment for lumbar fusion surgery. The most extensive
      outcomes data have been generated through FDA-regulated IDE trials for new
      technologies, which produce excellent data but are constrained by strict
      enrollment criteria and limited indications. This raises a question as to whether
      the excellent results seen in these IDE trials can be reproduced in standard
      clinical practice. PURPOSE: The purpose of this study was to analyze surgical
      results based upon standardized outcome tools, across a spectrum of
      interventions, for one- and two-level lumbar spine fusion procedures.
      DESIGN/SETTING: This study is a retrospective review of prospectively collected
      patient based outcomes data. PATIENT SAMPLE: Four hundred ninety-seven patients,
      who underwent 1- or 2-level lumbar spine fusion at five participating spine
      centers, utilizing a variety of surgical techniques. Enrollment criteria included
      available demographic, surgical and clinical outcome data. At a minimum, patients
      had pre-op and one year post-op SF-36 data. In many cases two-year post-op SF-36
      data and concomitant Oswestry Disability Index (ODI) data was available. OUTCOME
      MEASURES: SF36 and ODI. METHODS: The patient population included 270 females and
      227 males, with a mean age of 47 years. Sixty-five percent (N=324) had one level
      fusions and 35% (N=173) had two level fusions. Demographic data collected
      included age, gender, BMI, surgical history, smoking history and work status.
      Data was analyzed with repeated measures analysis of variance (ANOVA). RESULTS:
      SF-36 Physical Composite Score (PCS) improved a mean 9.9 points at one year post
      op and 9.5 points at two years post-op. ODI improved a mean 22.2 points at one
      year post-op and 22.1 points at two years post-op. SF-36 PCS data for surgical
      approach subgroups revealed greater improvement (p=.03) in the ALIF group as
      compared to the PSF, PLIF/TLIF, or 360 degrees fusion groups (12.6 points vs.
      8.8, 9.3, 8.4 points) at 1 year post-op. At 2 years post-op, there was greater
      improvement (p=.02) in the ALIF and PSF groups as compared to the PLIF/TLIF and
      360 degrees fusion groups (13.8 and 11.2 points vs. 7.7 and 6.3 points). SF-36
      PCS data demonstrated similar baseline scores for patients with and without prior
      decompression, but a significantly greater rate of improvement (11.3 vs. 7.2
      points, p=.002) for patients without prior lumbar decompression surgery. The ODI
      data indicated a significantly greater disability at baseline in the prior
      decompression group, with greater improvement (21.7 vs. 17.5 points) in patients
      without prior surgery. CONCLUSIONS: This study documents improved outcomes, based
      on SF-36 and ODI scores, in patients undergoing lumbar fusion for one and two
      level degenerative disc disease. The findings also demonstrate efficacy for all
      of the surgical techniques studied, suggesting that surgeons can appropriately
      select the surgical strategy with which they are most adept.

PMID- 16413444
TI  - Minimally disruptive decompression and transforaminal lumbar interbody fusion.
AB  - BACKGROUND: Posterior spinal procedures through tubular exposures have been
      described. However, tubes restrain visibility and require co-axial instrument
      manipulation, increasing difficulty and potentially compromising surgical
      results. An independent-blade retractor system overcomes the obstacles of working
      through a tube and has been used to perform minimally-disruptive decompression
      and instrumented tranforaminal lumbar interbody fusion (TLIF). PURPOSE: To
      evaluate the advantages to patient recovery and surgical efficacy of this
      technique. METHODS/RESULTS: Retrospective review of technique employing a
      minimally-disruptive approach to decompression and transforaminal lumber
      interbody fusion (TLIF). CONCLUSIONS: Minimally-disruptive decompression and
      instrumented TLIF can be performed in a safe and effective manner using an
      independent-blade retractor system. Relative to traditional-open techniques,
      surgical goals can be accomplished, but with the benefits of minimally-disruptive
      surgery.

PMID- 16413445
TI  - Biomechanical analysis of allograft bone treated with a novel tissue
      sterilization process.
AB  - BACKGROUND CONTEXT: Several methods to sterilize allograft bone exist, including
      gamma irradiation and freeze-drying, which can alter the mechanical properties of
      the graft. Efforts are under way to develop a method for processing osseous
      allograft that maintains structural integrity. Herein is presented one such
      method. PURPOSE: To analyze the mechanical properties, compared with nontreated
      controls, of a novel sterilization process for allograft cortical bone. STUDY
      DESIGN/SETTING: A controlled biomechanical evaluation of allograft bone under
      various types of loading after a novel sterilization treatment. PATIENT SAMPLE:
      Not applicable; basic science. OUTCOME MEASURES: The load to failure was recorded
      for both the study and control groups, and statistical analysis of these results
      was performed. Significance level (alpha) and power (beta) were set to 0.05 and
      0.90, respectively. Single-factor analysis of variance (ANOVA) was used to detect
      significant differences between the treated and untreated groups. A post
      experimental power analysis was performed for each of the response variables.
      METHODS: Cortical tibia and femur samples from seven cadaveric donors (mean age
      68.7 years) were treated with Biocleanse and compared with untreated samples with
      regard to density and strength. All samples were loaded to failure under
      diametral and biaxial compression, shear, and three-point bending. RESULTS:
      Statistical analysis was done on the density and failure stress for all modes of
      loading. ANOVA did not indicate a significant (p>.05) effect of treatment on the
      density except for the axial and biaxial specimens (p<.05). ANOVA analysis of
      failure stress demonstrated no significant differences (p>.05) between cortical
      bone treated with Biocleanse and untreated specimens under all four types of
      mechanical loading. Post-experimental power analysis revealed power to be greater
      than 0.9 for each test. CONCLUSIONS: Sterilization of allograft bone with
      Biocleanse does not significantly alter the mechanical properties when compared
      with untreated samples. The effect of this sterilization process on the
      osteoconductive and osteoinductive properties of allograft bone must be
      determined.

PMID- 16413446
TI  - Lateral mass screw fixation for cervical spine trauma: associated complications
      and efficacy in maintaining alignment.
AB  - BACKGROUND CONTEXT: Many studies have documented the efficacy of lateral mass
      screws, but there are no studies examining the alignment maintenance capability
      and few large studies examining the complications associated with the use of
      these devices in cervical spine trauma. PURPOSE: To evaluate complications and
      alignment maintenance capability associated with lateral mass screw placement for
      cervical spine trauma by one surgeon at one institution. STUDY DESIGN: A
      retrospective chart and radiograph review of adult patients who underwent lateral
      mass screw fixation after traumatic injuries to the cervical spine. PATIENT
      SAMPLE: Of 34 consecutive patients with cervical spine injuries who were treated
      surgically at a level-I regional trauma center, 29 met the inclusion criteria and
      formed the study group. OUTCOME MEASURES: Sagittal alignment, screw placement,
      and fusion were assessed on postoperative radiographs. METHODS: Inclusion
      criteria included an unstable cervical vertebral fracture or a fracture
      dislocation treated with posterior spine fusion and lateral mass instrumentation
      and a minimum follow-up of 24 months. A review of hospital charts, operative
      reports, clinic notes, and plain radiographs for the 29 patients was performed,
      with an emphasis on operative and postoperative complications and alignment
      maintenance. RESULTS: For 28 of the 29 patients, the mean change in sagittal
      alignment from the immediate postoperative to the most recent follow-up
      radiographic examination was 2 degrees (range, 0 degrees to 6 degrees ).
      Radiographically, there was one case of instrumentation/fixation failure and loss
      of sagittal alignment 3 months postoperatively. Other complications included one
      case of C5 nerve root injury and four wound infections. CONCLUSIONS: The use of
      lateral mass screws for traumatic injuries of the cervical spine is associated
      with excellent maintenance of alignment and minimal complications.

PMID- 16413447
TI  - Diving injuries of the cervical spine in amateur divers.
AB  - BACKGROUND CONTEXT: Diving injuries are the cause of potentially devastating
      trauma, primarily affecting the cervical spine. PURPOSE: Our purpose was to
      describe our experience with diving injuries treatment. STUDY DESIGN:
      Retrospective review. PATIENT SAMPLE: Twenty patients with diving injuries.
      OUTCOME MEASURES: Using the American Spinal Injury Association (ASIA) impairment
      scales as the primary outcome measure, the patients' neurological status before
      and after treatment was assessed. In this way we were able to draw conclusions
      about neurological improvement or deterioration in response to conservative or
      operative treatment. METHODS: We retrospectively reviewed 20 patients with diving
      injuries of the cervical spine who were admitted to our institute over a 34-year
      period from 1970 until 2004. RESULTS: The typical patient profile was of a young,
      healthy, athletic male who suffered an injury to the cervical spine after diving
      into shallow water. The number of cases corresponds to 2.6% of all admitted
      cervical spine injuries. All injures occurred between May and September. The most
      commonly fractured vertebrae were C5 and C6. Four patients were treated
      operatively and 16 conservatively. The indications for surgical treatment were
      posttraumatic instability and persistent neurological deficit. The mean follow-up
      of the patients was 17 years. Five patients died within the first month of their
      hospitalization and 1 patient died 1 year after his injury. Of the 14 patients
      who were available for follow-up 5 years past injury time, 6 improved
      neurologically and 8 remained unchanged in relation to their neurology upon
      admission. Of the 11 patients who were available for follow-up 10 years past
      injury time, 9 remained neurologically unchanged, 1 deteriorated, and 1 improved
      in relation to their neurology in the 5-year follow-up. CONCLUSION: Diving
      injuries of the cervical spine demonstrate high mortality and morbidity rates.
      Recovery depends on the severity of the initial neurological damage. Conservative
      treatment is justified in specific patients and can lead to improvement of the
      initial neurological deficit.

PMID- 16413448
TI  - Internal fixation without fusion of a flexion-distraction injury in the lower
      cervical spine of a three-year-old.
AB  - BACKGROUND: Reported surgical treatment of unstable pediatric cervical spine
      injuries typically involves posterior fusion with internal fixation, usually with
      posterior wiring. PURPOSE: To discuss management issues in the treatment of an
      unstable Salter-Harris type I pediatric cervical spine injury and surgical
      intervention without fusion. STUDY DESIGN: A case report. METHODS: Summary of the
      management of an unstable flexion-distraction injury in a 3-year-old child is
      presented with literature review. RESULTS: A rare unstable flexion distraction
      injury of the pediatric cervical spine was successfully treated with posterior
      wiring without fusion. The wires underwent fatigue failure and maintenance of
      motion achieved without instability at 2-year follow-up. CONCLUSIONS: In select
      physeal injuries of the pediatric cervical spine, internal fixation can provide
      stability while healing occurs, with avoidance of fusion and maintenance of
      motion.

PMID- 16413449
TI  - Traumatic fracture-dislocation of C5 on C6 through a previously solid multilevel
      anterior cervical discectomy and fusion: a case report and review of the
      literature.
AB  - BACKGROUND CONTEXT: Due to the underlying pathology and altered biomechanics,
      traumatic cervical fractures have been reported in patients with ankylosing
      spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), ossification
      of the posterior longitudinal ligament (OPLL), and combination of DISH and OPLL.
      However, incidence of a fracture-dislocation through a solid multilevel anterior
      cervical discectomy and fusion (ACDF) construct with no associated underlying
      pathology of AS, DISH, or OPLL but severe osteopenia has not, to the best
      knowledge of the authors, been reported in the medical literature. PURPOSE: To
      report the development of an unstable cervical spine fracture that occurred
      through a previous multilevel anterior cervical fusion and the challenges
      associated with the diagnosis and surgical management of these uncommon lesions.
      STUDY DESIGN/SETTING: A case report and review of the literature. METHODS: A case
      report entailing the clinical history, operative management, and postoperative
      course of a 72-year-old male patient with no known AS, DISH, or OPLL who suffered
      a cervical spine fracture-dislocation, secondary to a motor vehicle accident,
      through a previous solid three-level ACDF that was performed 20 years earlier.
      RESULTS: The patient underwent emergent reduction and realignment of the cervical
      fracture-dislocation, eventual posterior spinal fusion and stabilization with
      rigid segmental internal fixation, and application of external halo
      immobilization. At recent follow-up, he has radiographic evidence of fusion and
      maintenance of sagittal alignment without loss of reduction. CONCLUSIONS:
      Multilevel cervical fusion constructs are susceptible to traumatic injuries. Many
      of the same challenges in the management of the previously fused ACDF patient,
      who sustains a fracture-dislocation, are similar to those found in the patient
      with mass-inflammatory conditions or metabolic disorders, such as AS, DISH, or
      OPLL. In many cases, this includes severe osteopenia, long unstable fusion
      segments, and difficulties associated with prolonged halo vest immobilization. As
      a result, preoperative surgical planning should take into consideration the
      difficulties in achieving fracture reduction, decompression, and proper
      stabilization.

PMID- 16413450
TI  - Pain, malingering and the WAIS-III Working Memory Index.
AB  - BACKGROUND CONTEXT: Pain patients often report cognitive symptoms, and many will
      include them in their claims of disability. There is empirical evidence that
      patients with pain do experience problems on attention-demanding cognitive tasks,
      but the results are mixed and the potential impact of exaggeration in the context
      of pain-related litigation has not been addressed. PURPOSE: 1) Examine the impact
      of pain and malingering on attention; 2) determine if the Working Memory Index
      (WMI) of the Wechsler Adult Intelligence Scale-3 (WAIS-III) can reliably detect
      malingering. STUDY DESIGN/SETTING: Study 1: simulator design; Study 2: clinical
      known-groups design. PATIENT SAMPLE: Study 1 used healthy college students; Study
      2 used chronic pain patients and neurological patients. OUTCOME MEASURES: The WMI
      and its constituent subtests. METHODS: Study 1: College students were
      administered the WMI under three conditions: standard administration, with cold
      pressor induced pain, or with instructions to simulate impairment due to pain.
      Study 2: Known-groups design in which the WMI was examined in non-malingering and
      definite malingering chronic pain patients, non-malingering moderate-severe
      traumatic brain injury, and memory disorder patients seen for routine
      psychological evaluation. Malingering was operationalized using published
      criteria. RESULTS: There were no group differences in WMI or its subtests among
      non-malingering groups, but some individual clinical patients with pain did score
      at a level suggestive of attentional impairment. The lowest scores were found in
      the simulated malingering college students and definite malingering clinical pain
      groups, in which about half scored worse than 95% of the non-malingering clinical
      patients. CONCLUSIONS: This study demonstrated that even when controlling for
      exaggeration some pain patients do exhibit problems with attentional function.
      However, significant impairment in WMI performance (eg, index score<or=70),
      particularly in the absence of brain dysfunction, cannot reasonably be attributed
      to the effects of either acute or chronic pain, even at moderate to severe
      levels, and likely reflects intentional exaggeration.

PMID- 16413451
TI  - An independent AGREE evaluation of the Occupational Medicine Practice Guidelines.
AB  - BACKGROUND AND CONTEXT: A large number of practice guidelines are being produced
      by numerous organizations. Health-care professionals need to critically evaluate
      these practice guidelines to understand whether they are well constructed and
      representative of the preponderance of evidence. The guideline development
      process should be precise and rigorous to ensure that the results are
      reproducible and not vague. PURPOSE: To evaluate the quality of the second
      edition of the practice guidelines published by the American College of
      Occupational and Environmental Medicine (ACOEM Guidelines). STUDY DESIGN/SETTING:
      Four appraisers used the AGREE (Appraisal of Guidelines Research and Evaluation)
      guideline evaluation instrument to evaluate the ACOEM Guidelines. METHODS: The
      Guidelines were evaluated with the AGREE guideline evaluation instrument. The
      AGREE instrument has been widely adopted around the world, and the authors
      recommended that it be adopted as the standard of guideline construction process
      evaluation in the United States. The instrument standardizes the quantitative
      assessment of quality for a guideline's development process across six domains
      that include: scope and purpose, stakeholder involvement, rigor of development,
      clarity and presentation, application, and editorial independence. Scores from
      four assessors were collected and interpreted. Additionally, each evaluator
      selected one of four global assessment choices: "strongly recommended for use in
      practice," "recommended for use with some modification or proviso," "not
      recommended as suitable for use in practice," or "unsure". RESULTS: The ACOEM
      Guidelines scored highest in the dimensions that evaluated reporting of the
      guideline's scope and purpose (79.63) as well as clarity and presentation
      (86.81). The guideline scored much lower in the remaining areas that included
      stakeholder involvement (46.06), rigor of development (26.59), application
      (31.48), and editorial independence (19.17). The global assessment was unanimous
      with all four evaluators assessing the guideline as recommend with proviso.
      CONCLUSIONS: Many of the Guidelines recommendations were consistent with current
      literature and guidelines; however, the AGREE assessment instrument evaluates the
      guideline development process and not the content. All the evaluators thought the
      content of the guidelines was substantially better than the documentation of the
      guideline construction process. The ACOEM Guidelines appear to have content
      consistent with their stated objectives, but the reporting of the guidelines
      construction process, particularly the rigor of recommendation development, is
      flawed, and the recommendations may not be valid owing to possible evidence
      selection deficiencies. The reader should consider these flaws and limitations
      when using the guideline. The reader should consider utilizing guidelines of
      higher quality when possible. Future guidelines should incorporate better
      reporting and give closer attention to guideline construction.

PMID- 16413452
TI  - Less invasive posterior fixation method following transforaminal lumbar interbody
      fusion: a biomechanical analysis.
AB  - BACKGROUND CONTEXT: Current surgical trends increasingly emphasize the
      minimization of surgical exposure and tissue morbidity. Previous research
      questioned the ability of unilateral pedicle screw instrumentation to adequately
      stabilize posterior fusion constructs. No study to date has addressed the effects
      of reduced posterior instrumentation mass on interbody construct techniques.
      Unilateral surgical exposure for transforaminal lumbar interbody fusion (TLIF)
      allows ipsilateral pedicle screw placement. Theoretically, percutanous
      contralateral facet screw placement could provide supplemental construct support
      without additional surgical exposure. PURPOSE: Identify the biomechanical effects
      of reduced spinal fusion instrumentation mass on interbody construct stability.
      STUDY DESIGN: An in vitro biomechanical study using human lumbar spines comparing
      stability of TLIF constructs augmented by: (1) bilateral pedicle screw fixation,
      (2) unilateral pedicle screw fixation, or (3) a novel unilateral pedicle screw
      fixation supplemented with contralateral facet screw construct. METHODS: Seven
      fresh frozen human cadaveric specimens were tested in random construct order in
      flexion/extension, lateral bending, and axial rotation using +/-5.0 Nm torques
      and 50 N axial compressive loads. Analysis of torque rotation curves determined
      construct stability. Using paired statistical methods, comparison of construct
      stiffness and total range of motion within each specimen were performed using the
      Wilcoxon signed ranks test with a Holm-Sidak multiple comparison procedure
      (alpha=0.05). RESULTS: In flexion/extension, lateral bending, and axial rotation,
      there were no measurable differences in either stiffness or range of motion
      between the standard bilateral pedicle screw and the novel construct after TLIF.
      After TLIF, the unilateral pedicle screw construct provided only half of the
      improvement in stiffness compared with bilateral or novel constructs and allows
      for significant off-axis rotational motions, which could be detrimental to
      stability and the promotion for fusion. CONCLUSIONS: All tested TLIF constructs
      with posterior instrumentation decreased segmental range of motion and increased
      segmental stiffness. While placing unilateral posterior instrumentation decreases
      overall implant bulk and dissection, it allows for significantly increased
      segmental range of motion, less stiffness, and produces off-axis movement. The
      technique of contralateral facet screw placement provides the surgical advantages
      of unilateral pedicle screw placement with stability comparable to TLIF with
      bilateral pedicle screws.

PMID- 16413453
TI  - Multiple cerebellar hemorrhagic infarctions following surgery for a huge
      atlantoaxial neurinoma.
AB  - BACKGROUND CONTEXT: There have been only five reported cases with cerebellar
      hemorrhagic infarction after spinal surgery, and the underlying pathomechanism
      remains obscure. PURPOSE: To describe a case with multiple cerebellar hemorrhagic
      infarctions after surgery for a huge atlantoaxial neurinoma. STUDY
      DESIGN/SETTING: Case report METHODS: A 36-year-old man underwent uneventful
      surgery for a huge atlantoaxial neurinoma. After surgery, the patient was
      lethargic with slurred speech and subsequently developed cerebellar symptoms,
      although preoperative myelopathic symptoms did not worsen. The clinical and
      radiological findings are presented, and possible causes of the hemorrhages are
      discussed. RESULTS: Magnetic resonance imaging of the brain after surgery showed
      multiple cerebellar hemorrhagic infarctions. However, magnetic resonance
      angiography revealed no occlusion or stenosis in the vertebrobasilar system, and
      a duplex scan of the neck vessels confirmed normal flow in the vertebral arteries
      after surgery. In response to the conservative treatment, the patient exhibited
      neurological recovery with disappearance of cerebellar symptoms. CONCLUSIONS: In
      the present case with multiple cerebellar hemorrhagic infarctions, venous
      infarction appears more likely to be the cause of cerebellar hemorrhagic
      infarction than arterial infarction. The most likely underlying pathomechanism is
      a cerebellar venous disturbance precipitated by loss of a large amount of
      cerebrospinal fluid, although the exact etiology remains elusive.

PMID- 16413455
TI  - Retrievable inferior vena cava filter embolizes to right ventricle/pulmonary
      outflow tract.

PMID- 16413456
TI  - To the editor.

PMID- 16413458
TI  - To the editor.

PMID- 16413459
TI  - To the editor.

PMID- 16413454
TI  - Lumbar teratoma presenting intradural and extramedullary extension in a neonate.
AB  - BACKGROUND CONTEXT: The association of teratomas and spinal malformations such as
      spina bifida, partial sacral agenesis, hemivertebrae, and diastematomyelia has
      been described in the literature. Reported cases, however, are mainly presacral
      or sacrococcygeal with an extremely rare presentation of intradural extension.
      PURPOSE: A case of lumbar teratoma with an intradural extension and
      extramedullary component and the clinical outcome following surgical treatment
      are reported. STUDY DESIGN/SETTING: To our knowledge, among the reported teratoma
      cases with an intradural extension and extramedullary component, our case has a
      distinguishing feature regarding the involvement of the lumbar spine. It is also
      the first case, showing no neurological deficit during the postoperative period.
      METHODS: A full-term, female infant presented with a 30 x 30 x 10 mm lumbar mass
      covered with normal skin. The mass contained an irregular, bone-like, hard and
      mobile material accompanying cystic components. Magnetic resonance imaging
      revealed a total closure defect of the first and second lumbar laminae and a
      subcutaneous mass with intradural extension. The lesion was found to penetrate
      the dural sac through an extended exposure from T12 to L3. There was no firm
      attachment of the intradural, extramedullary component of the lesion. Total
      removal of the tumor was achieved. RESULTS: The patient was discharged on day 7
      without any neurological deficit or sign of hydrocephalus. The pathological
      examination showed a benign teratoma containing mature cartilage, muscle, adipose
      tissue, and glandular tissue. Follow-up at 2 years showed no recurrence or
      neurological deficit and a normal sphincter tone. Urodynamic evaluation was
      within normal limits. CONCLUSION: Accompanying a spinal dysraphic state, the
      mature teratoma in our case may support the idea of a tumor actually arising from
      a dysraphism and growing outward to produce the mass.

PMID- 16413460
TI  - To the editor.

PMID- 16413463
TI  - p63 and p73: teammates or adversaries?
AB  - The status and interrelationship of p53 family members are critical elements in
      tumor progression. An intriguing paper in this issue of Cancer Cell (Rocco et
      al., 2006) reveals a new twist in the interactions between p63 and p73 following
      DNA damage, underscoring a role for p73 in the proapoptotic regulation of Puma,
      Noxa, and Bcl-2 in head and neck squamous cell carcinomas (HNSCC). These data
      define a pathway in which deltaNp63alpha promotes survival in squamous epithelial
      malignancy by repressing a p73-dependent proapoptotic transcriptional program,
      suggesting that p63 levels and p73 status may be key determinants of tumor
      response in patients with HNSCC.

PMID- 16413464
TI  - Is Cyclin D1-CDK4 kinase a bona fide cancer target?
AB  - Previous studies have demonstrated that mice lacking Cyclin D1 were refractory to
      mammary tumor development induced by the c-neu/erbB-2 oncogene, the rodent
      ortholog of the HER-2 receptor frequently overexpressed in human breast
      carcinomas. Two new studies in this issue of Cancer Cell provide additional
      evidence on this issue. Knockin mice expressing a mutant form of Cyclin D1 that
      binds to Cdk4/6 but cannot activate their catalytic activity are resistant to c
      neu/erbB-2 tumorigenesis in spite of undergoing normal epithelial cell expansion
      during pregnancy. Moreover, knockdown of Cdk4 in mammary tumor cells abrogates
      tumor formation. These observations provide new compelling evidence that
      inhibition of Cyclin D1-Cdk4/6 kinases might be beneficial for cancer therapy.

PMID- 16413465
TI  - Fly Src: the Yin and Yang of tumor invasion and tumor suppression.
AB  - The non-receptor tyrosine kinase Src is inactivated by the C-terminal Src kinase
      Csk. In a recent paper in Developmental Cell, Vidal et al. show that loss of
      Drosophila Csk (dCsk) in a large field of cells results in cell proliferation and
      disorganization of tissue architecture. In contrast, local inactivation of dCsk
      in a small field of cells results in loss of cells that are adjacent to normal
      tissue. This loss occurs by basal migration and death by apoptosis. These
      findings may shed light on mechanisms that restrain tumor initiation.

PMID- 16413466
TI  - Connecting COX-2 and Wnt in cancer.
AB  - Both the cyclooxygenase-2 (COX-2) and Wnt signaling cascades are active in the
      majority of colorectal cancers. Nevertheless, a direct link between these two key
      pathways has remained elusive. Recent reports show that one of the bioactive
      products of COX-2, prostaglandin E2, activates components of the canonical Wnt
      signaling system. The findings reviewed below reveal important crosstalk between
      these pathways, which may provide opportunities for the development of new drugs
      for treatment and/or prevention of colorectal cancer.

PMID- 16413467
TI  - BuCy RAFs drive cells into MEK addiction.
AB  - RAF research is booming since the discovery of mutant B-RAF in approximately 8%
      of human cancer. One reason for the excitement is the availability of RAF
      targeted therapies. RAF inhibitors have been developed because RAF functions at a
      convergence point of signal transduction. Two recent papers by the groups of
      Rosen and Marais dramatically advance our understanding of RAF oncogenes in human
      tumors. The results confirm that the mitogenic cascade (RAF-MEK-ERK) is essential
      for RAF transformation, that RAF kinases work in concert, and that RAF
      transformed cells are hooked on MEK, making them sensitive to growth inhibition
      by kinase inhibitors.

PMID- 16413468
TI  - Cyclin D1-dependent kinase activity in murine development and mammary
      tumorigenesis.
AB  - Cyclin D1 is a multifunctional protein that activates CDK4 and CDK6, titrates
      Cip/Kip CDK inhibitors to increase CDK2 activity, and modulates the function of
      certain transcription factors. To specifically test the importance of cyclin D1
      associated kinase activity, we generated "knockin" mice expressing mutant cyclin
      D1 deficient in activating CDK4/6. The development of several cyclin D1-dependent
      compartments, including mammary glands, proceeds relatively normally in these
      animals, demonstrating that cyclin D1-associated kinase activity is largely
      dispensable for development of these tissues. Strikingly, knockin mice were
      resistant to breast cancers initiated by ErbB-2. These results demonstrate a
      differential requirement for cyclin D1-CDK4/6 kinase activity in development
      versus tumorigenesis and strongly support cyclin D1-dependent kinase activity as
      a specific therapeutic target in breast cancer.

PMID- 16413469
TI  - Requirement for CDK4 kinase function in breast cancer.
AB  - Cyclin D1 is overexpressed in the majority of human breast cancers. We previously
      found that mice lacking cyclin D1 are resistant to mammary carcinomas triggered
      by the ErbB-2 oncogene. In this study, we investigated which function of cyclin
      D1 is required for ErbB-2-driven mammary oncogenesis. We report that the ability
      of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role
      for cyclin D1 in breast cancer formation. We also found that the continued
      presence of CDK4-associated kinase activity is required to maintain breast
      tumorigenesis. We analyzed primary human breast cancers and found high cyclin D1
      levels in a subset (approximately 25%) of ErbB-2-overexpressing tumors. We
      propose that this subset of breast cancer patients might benefit from inhibiting
      CDK4 kinase.

PMID- 16413470
TI  - ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and
      sprouting during angiogenesis.
AB  - Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the
      tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic
      tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase
      results in loss of bipolarity, detachment, and cell death of isolated endothelial
      cells and retraction of sprouting tubules. These effects are the consequence of
      upregulated Rho-kinase signaling. Transient inhibition of Rho-kinase rescues the
      effects of ERK-MAPK inhibition in vitro and in vivo, promotes sprouting, and
      increases vessel length in tumors. We propose a regulatory role of Rho-kinase by
      ERK-MAPK during angiogenesis that acts through the control of actomyosin
      contractility. Our data delineate a mechanism by which ERK-MAPK promotes
      endothelial cell survival and sprouting by downregulating Rho-kinase signaling.

PMID- 16413472
TI  - Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop
      acute myeloid leukemia.
AB  - The acute myeloid leukemia (AML)-associated CBF beta-SMMHC fusion protein impairs
      hematopoietic differentiation and predisposes to leukemic transformation. The
      mechanism of leukemia progression, however, is poorly understood. In this study,
      we report a conditional Cbfb-MYH11 knockin mouse model that develops AML with a
      median latency of 5 months. Cbf beta-SMMHC expression reduced the multilineage
      repopulation capacity of hematopoietic stem cells (HSCs) while maintaining their
      numbers under competitive conditions. The fusion protein induced abnormal myeloid
      progenitors (AMPs) with limited proliferative potential but leukemic
      predisposition similar to that of HSCs in transplanted mice. In addition, Cbf
      beta-SMMHC blocked megakaryocytic maturation at the CFU-Meg to megakaryocyte
      transition. These data show that a leukemia oncoprotein can inhibit
      differentiation and proliferation while not affecting the maintenance of long
      term HSCs.

PMID- 16413473
TI  - US biomedical research under siege.
AB  - The stagnation of biomedical research funding in the US is placing great pressure
      on the research enterprise. It is time to consider some radical solutions.

PMID- 16413471
TI  - p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent
      apoptosis.
AB  - We demonstrate that deltaNp63alpha is an essential survival factor in head and
      neck squamous cell carcinoma (HNSCC) through its ability to suppress p73
      dependent apoptosis. Inhibition of endogenous p63 expression by RNAi induces
      apoptosis selectively in HNSCC cells that overexpress deltaNp63alpha. Knockdown
      of p63 induces the proapoptotic bcl-2 family members Puma and Noxa, and both
      their induction and subsequent cell death are p53 independent but require
      transactivating isoforms of p73. Inhibition of p73-dependent transcription by
      deltaNp63alpha involves both direct promoter binding and physical interaction
      with p73. In HNSCC cells lacking endogenous deltaNp63alpha expression, bcl-2 is
      instead upregulated and can suppress p73-mediated death. Together, these data
      define a pathway whereby deltaNp63alpha promotes survival in squamous epithelial
      malignancy by repressing a p73-dependent proapoptotic transcriptional program.

PMID- 16413474
TI  - Wolfram Horz 1944-2005.

PMID- 16413475
TI  - Pathogens reWritE Rho's rules.
AB  - Many bacterial pathogens use a specialized "type III" secretion system to deliver
      virulence effector proteins into host mammalian cells. In this issue of Cell,
      Alto et al. (2006) describe a new family of effectors that share a WxxxE sequence
      motif. These effectors directly stimulate host signaling pathways by mimicking
      activated Ras-like cellular GTPases.

PMID- 16413476
TI  - An SDF-1 trap for myeloid cells stimulates angiogenesis.
AB  - In this issue of Cell, Grunewald et al. (2005) examine the role of hematopoietic
      cells in the formation of new blood vessels. They show that organ-specific
      expression of vascular endothelial growth factor (VEGF) is sufficient to mobilize
      and recruit hematopoietic cells from the bone marrow to the blood, but retention
      of the proangiogenic subpopulation of hematopoietic cells in peripheral organs
      requires an additional factor, stromal-derived factor 1 (SDF-1).

PMID- 16413477
TI  - Transcription factor target practice.
AB  - In this issue of Cell, Hallikas et al. (2006) and Wei et al. (2006) describe
      different ways of identifying direct targets of transcription factors and their
      corresponding regulatory sequences in the genome. Although still under
      development, these studies provide an efficient way to decipher regulatory
      networks.

PMID- 16413478
TI  - RISC-y Memories.
AB  - Local protein synthesis in the synapse is required for synaptic plasticity and
      has been implicated in learning and memory. However, direct evidence that
      behavioral training induces local protein synthesis has been lacking. In this
      issue of Cell, Ashraf et al. (2006) observe persistent local protein synthesis in
      the antennal lobe synapses of the fruit fly following olfactory-avoidance
      learning. This protein synthesis is regulated by the RNA-induced silencing
      complex (RISC).

PMID- 16413479
TI  - Lingering mysteries of ubiquitin-chain assembly.
AB  - The small protein ubiquitin is often linked to substrates as a polymer. Such
      polymers vary in both linkage and length, which has important consequences for
      their function. Surprisingly, the mechanisms of ubiquitin-chain assembly are
      still not known. Deciphering them will shed light on why substrates differ in the
      extent and timing of polyubiquitin modification and how ancillary ubiquitination
      factors function.

PMID- 16413480
TI  - Protein sensors for membrane sterols.
AB  - Cholesterol is an essential component of animal cell membranes, and its
      concentration is tightly controlled by a feedback system that operates at
      transcriptional and posttranscriptional levels. Here, we discuss recent advances
      that explain how cells employ an ensemble of membrane-embedded proteins to
      monitor sterol concentrations and adjust sterol synthesis and uptake.

PMID- 16413481
TI  - Genome-wide prediction of mammalian enhancers based on analysis of transcription
      factor binding affinity.
AB  - Understanding the regulation of human gene expression requires knowledge of the
      "second genetic code," which consists of the binding specificities of
      transcription factors (TFs) and the combinatorial code by which TF binding sites
      are assembled to form tissue-specific enhancer elements. Using a novel high
      throughput method, we determined the DNA binding specificities of GLIs 1-3, Tcf4,
      and c-Ets1, which mediate transcriptional responses to the Hedgehog (Hh), Wnt,
      and Ras/MAPK signaling pathways. To identify mammalian enhancer elements
      regulated by these pathways on a genomic scale, we developed a computational
      tool, enhancer element locator (EEL). We show that EEL can be used to identify Hh
      and Wnt target genes and to predict activated TFs based on changes in gene
      expression. Predictions validated in transgenic mouse embryos revealed the
      presence of multiple tissue-specific enhancers in mouse c-Myc and N-Myc genes,
      which has implications for organ-specific growth control and tumor-type
      specificity of oncogenes.

PMID- 16413482
TI  - The crystal structure of yeast protein disulfide isomerase suggests cooperativity
      between its active sites.
AB  - Protein disulfide isomerase plays a key role in catalyzing the folding of
      secretory proteins. It features two catalytically inactive thioredoxin domains
      inserted between two catalytically active thioredoxin domains and an acidic C
      terminal tail. The crystal structure of yeast PDI reveals that the four
      thioredoxin domains are arranged in the shape of a twisted "U" with the active
      sites facing each other across the long sides of the "U." The inside surface of
      the "U" is enriched in hydrophobic residues, thereby facilitating interactions
      with misfolded proteins. The domain arrangement, active site location, and
      surface features strikingly resemble the Escherichia coli DsbC and DsbG protein
      disulfide isomerases. Biochemical studies demonstrate that all domains of PDI,
      including the C-terminal tail, are required for full catalytic activity. The
      structure defines a framework for rationalizing the differences between the two
      active sites and their respective roles in catalyzing the formation and
      rearrangement of disulfide bonds.

PMID- 16413483
TI  - Systems analyses reveal two chaperone networks with distinct functions in
      eukaryotic cells.
AB  - Molecular chaperones assist the folding of newly translated and stress-denatured
      proteins. In prokaryotes, overlapping sets of chaperones mediate both processes.
      In contrast, we find that eukaryotes evolved distinct chaperone networks to carry
      out these functions. Genomic and functional analyses indicate that in addition to
      stress-inducible chaperones that protect the cellular proteome from stress,
      eukaryotes contain a stress-repressed chaperone network that is dedicated to
      protein biogenesis. These stress-repressed chaperones are transcriptionally,
      functionally, and physically linked to the translational apparatus and associate
      with nascent polypeptides emerging from the ribosome. Consistent with a function
      in de novo protein folding, impairment of the translation-linked chaperone
      network renders cells sensitive to misfolding in the context of protein synthesis
      but not in the context of environmental stress. The emergence of a translation
      linked chaperone network likely underlies the elaborate cotranslational folding
      process necessary for the evolution of larger multidomain proteins characteristic
      of eukaryotic cells.

PMID- 16413484
TI  - The processivity of multiubiquitination by the APC determines the order of
      substrate degradation.
AB  - The anaphase-promoting complex (APC) coordinates mitosis and G1 by sequentially
      promoting the degradation of key cell-cycle regulators. Following the degradation
      of its substrates in G1, the APC catalyzes the autoubiquitination of its E2
      UbcH10. This stabilizes cyclin A and allows it to inactivate APC(Cdh1). How the
      APC establishes this complex temporal sequence of ubiquitinations, referred to as
      substrate ordering, is not understood. Here we show that substrate ordering
      depends on the relative processivity of substrate multiubiquitination by the APC.
      Processive substrates obtain ubiquitin chains in a single APC binding event. The
      multiubiquitination of distributive substrates requires multiple rounds of APC
      binding, which render it sensitive to lower APC concentrations, competition by
      processive substrates, and deubiquitination. Consequently, more processive
      substrates are preferentially multiubiquitinated in vitro and degraded earlier in
      vivo. The processivity of multiubiquitination is strongly influenced by the D box
      within the substrate, suggesting that substrate ordering is established by a
      mechanism intrinsic to APC and its substrates and similar to kinetic
      proofreading.

PMID- 16413485
TI  - Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a
      propeller cluster in ubiquitin ligase.
AB  - The DDB1-Cul4A ubiquitin ligase complex promotes protein ubiquitination in
      diverse cellular functions and is reprogrammed by the V proteins of
      paramyxoviruses to degrade STATs and block interferon signaling. Here we report
      the crystal structures of DDB1 alone and in complex with the simian virus 5 V
      protein. The DDB1 structure reveals an intertwined three-propeller cluster, which
      contains two tightly coupled beta propellers with a large pocket in between and a
      third beta propeller flexibly attached on the side. The rigid double-propeller
      fold of DDB1 is targeted by the viral V protein, which inserts an entire helix
      into the double-propeller pocket, whereas the third propeller domain docks DDB1
      to the N terminus of the Cul4A scaffold. Together, these results not only provide
      structural insights into how the virus hijacks the DDB1-Cul4A ubiquitin ligase
      but also establish a structural framework for understanding the multiple
      functions of DDB1 in the uniquely assembled cullin-RING E3 machinery.

PMID- 16413486
TI  - Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through
      epithelial tight junctions.
AB  - Group B coxsackieviruses (CVBs) must cross the epithelium as they initiate
      infection, but the mechanism by which this occurs remains uncertain. The
      coxsackievirus and adenovirus receptor (CAR) is a component of the tight junction
      and is inaccessible to virus approaching from the apical surface. Many CVBs also
      interact with the GPI-anchored protein decay-accelerating factor (DAF). Here, we
      report that virus attachment to DAF on the apical cell surface activates Abl
      kinase, triggering Rac-dependent actin rearrangements that permit virus movement
      to the tight junction. Within the junction, interaction with CAR promotes
      conformational changes in the virus capsid that are essential for virus entry and
      release of viral RNA. Interaction with DAF also activates Fyn kinase, an event
      that is required for the phosphorylation of caveolin and transport of virus into
      the cell within caveolar vesicles. CVBs thus exploit DAF-mediated signaling
      pathways to surmount the epithelial barrier.

PMID- 16413487
TI  - Identification of a bacterial type III effector family with G protein mimicry
      functions.
AB  - Many bacterial pathogens use the type III secretion system to inject "effector"
      proteins into host cells. Here, we report the identification of a 24 member
      effector protein family found in pathogens including Salmonella, Shigella, and
      enteropathogenic E. coli. Members of this family subvert host cell function by
      mimicking the signaling properties of Ras-like GTPases. The effector IpgB2
      stimulates cellular responses analogous to GTP-active RhoA, whereas IpgB1 and Map
      function as the active forms of Rac1 and Cdc42, respectively. These effectors do
      not bind guanine nucleotides or have sequences corresponding the conserved GTPase
      domain, suggesting that they are functional but not structural mimics. However,
      several of these effectors harbor intracellular targeting sequences that
      contribute to their signaling specificities. The activities of IpgB2, IpgB1, and
      Map are dependent on an invariant WxxxE motif found in numerous effectors leading
      to the speculation that they all function by a similar molecular mechanism.

PMID- 16413488
TI  - Embryonic dorsal-ventral signaling: secreted frizzled-related proteins as
      inhibitors of tolloid proteinases.
AB  - Here we report an unexpected role for the secreted Frizzled-related protein
      (sFRP) Sizzled/Ogon as an inhibitor of the extracellular proteolytic reaction
      that controls BMP signaling during Xenopus gastrulation. Microinjection
      experiments suggest that the Frizzled domain of Sizzled regulates the activity of
      Xolloid-related (Xlr), a metalloproteinase that degrades Chordin, through the
      following molecular pathway: Szl -| Xlr -| Chd -| BMP --> P-Smad1 --> Szl. In
      biochemical assays, the Xlr proteinase has similar affinities for its endogenous
      substrate Chordin and for its competitive inhibitor Sizzled, which is resistant
      to enzyme digestion. Extracellular levels of Sizzled and Chordin in the gastrula
      embryo and enzyme reaction constants were all in the 10(-8) M range, consistent
      with a physiological role in the regulation of dorsal-ventral patterning. Sizzled
      is also a natural inhibitor of BMP1, a Tolloid metalloproteinase of medical
      interest. Furthermore, mouse sFRP2 inhibited Xlr, suggesting a wider role for
      this molecular mechanism.

PMID- 16413489
TI  - Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly.
AB  - New blood vessels are initially formed through the assembly or sprouting of
      endothelial cells, but the recruitment of supporting pericytes and vascular
      smooth muscle cells (mural cells) ensures the formation of a mature and stable
      vascular network. Defective mural-cell coverage is associated with the poorly
      organized and leaky vasculature seen in tumors or other human diseases. Here we
      report that mural cells require ephrin-B2, a ligand for Eph receptor tyrosine
      kinases, for normal association with small-diameter blood vessels (microvessels).
      Tissue-specific mutant mice display perinatal lethality; vascular defects in
      skin, lung, gastrointestinal tract, and kidney glomeruli; and abnormal migration
      of smooth muscle cells to lymphatic capillaries. Cultured ephrin-B2-deficient
      smooth muscle cells are defective in spreading, focal-adhesion formation, and
      polarized migration and show increased motility. Our results indicate that the
      role of ephrin-B2 and EphB receptors in these processes involves Crk-p130(CAS)
      signaling and suggest that ephrin-B2 has some cell-cell-contact-independent
      functions.

PMID- 16413490
TI  - VEGF-induced adult neovascularization: recruitment, retention, and role of
      accessory cells.
AB  - Adult neovascularization relies on the recruitment of circulating cells, but
      their angiogenic roles and recruitment mechanisms are unclear. We show that the
      endothelial growth factor VEGF is sufficient for organ homing of circulating
      mononuclear myeloid cells and is required for their perivascular positioning and
      retention. Recruited bone marrow-derived circulating cells (RBCCs) summoned by
      VEGF serve a function distinct from endothelial progenitor cells. Retention of
      RBCCs in close proximity to angiogenic vessels is mediated by SDF1, a chemokine
      induced by VEGF in activated perivascular myofibroblasts. RBCCs enhance in situ
      proliferation of endothelial cells via secreting proangiogenic activities
      distinct from locally induced activities. Precluding RBCCs strongly attenuated
      the proangiogenic response to VEGF and addition of purified RBCCs enhanced
      angiogenesis in excision wounds. Together, the data suggest a model for VEGF
      programmed adult neovascularization highlighting the essential paracrine role of
      recruited myeloid cells and a role for SDF1 in their perivascular retention.

PMID- 16413491
TI  - Synaptic protein synthesis associated with memory is regulated by the RISC
      pathway in Drosophila.
AB  - Long-lasting forms of memory require protein synthesis, but how the pattern of
      synthesis is related to the storage of a memory has not been determined. Here we
      show that neural activity directs the mRNA of the Drosophila Ca(2+),
      Calcium/Calmodulin-dependent Kinase II (CaMKII), to postsynaptic sites, where it
      is rapidly translated. These features of CaMKII synthesis are recapitulated
      during the induction of a long-term memory and produce patterns of local protein
      synthesis specific to the memory. We show that mRNA transport and synaptic
      protein synthesis are regulated by components of the RISC pathway, including the
      SDE3 helicase Armitage, which is specifically required for long-lasting memory.
      Armitage is localized to synapses and lost in a memory-specific pattern that is
      inversely related to the pattern of synaptic protein synthesis. Therefore, we
      propose that degradative control of the RISC pathway underlies the pattern of
      synaptic protein synthesis associated with a stable memory.

PMID- 16413492
TI  - A global map of p53 transcription-factor binding sites in the human genome.
AB  - The ability to derive a whole-genome map of transcription-factor binding sites
      (TFBS) is crucial for elucidating gene regulatory networks. Herein, we describe a
      robust approach that couples chromatin immunoprecipitation (ChIP) with the paired
      end ditag (PET) sequencing strategy for unbiased and precise global localization
      of TFBS. We have applied this strategy to map p53 targets in the human genome.
      From a saturated sampling of over half a million PET sequences, we characterized
      65,572 unique p53 ChIP DNA fragments and established overlapping PET clusters as
      a readout to define p53 binding loci with remarkable specificity. Based on this
      information, we refined the consensus p53 binding motif, identified at least 542
      binding loci with high confidence, discovered 98 previously unidentified p53
      target genes that were implicated in novel aspects of p53 functions, and showed
      their clinical relevance to p53-dependent tumorigenesis in primary cancer
      samples.

PMID- 16413493
TI  - Effect of short and long exposure duration and dual-tasking on a global-local
      task.
AB  - Past research has demonstrated a global advantage in responses to visually
      presented hierarchical stimuli such that, on incongruent trials, the global form
      interferes with responses to the local level [Kimchi, R. (1992). Primacy of
      wholistic processing and global/local paradigm: A critical review. Psychological
      Bulletin, 112, 24-38]. In Experiment 1, 32 adults performed alternating blocks of
      global or local identification of hierarchical letter stimuli in which the global
      and local letters were congruent, incongruent, or neutral, and were presented at
      either a short (17 ms) or long (100 ms) exposure duration. A global advantage was
      demonstrated at both durations. In the local-directed task, interference on
      incongruent, relative to neutral, trials was observed at both exposure durations,
      but facilitation on congruent trials, relative to neutral trials, was present
      only when stimuli were presented at the long exposure duration. In Experiment 2,
      global or local identification was performed by another group of 24 adults at
      either a long or short exposure duration, and also under conditions of full
      attention (FA) or dual-task (DT) conditions with a digit-monitoring task. Under
      FA, we again found significant interference at both exposure durations, but
      facilitation only at the long exposure duration. Under DT conditions, the pattern
      of facilitation and interference at the short duration remained unchanged. At the
      long duration, however, dual-tasking eliminated interference in the RT but not
      error data, while facilitation was present in both sets of data. Results are in
      line with a perceptual account of the global advantage, and suggest that
      facilitation requires consciously-mediated processes, whereas interference does
      not.

PMID- 16413494
TI  - Polyplex-embedding in polyelectrolyte multilayers for gene delivery.
AB  - In this work, incorporation of plasmid DNA, pre-complexed with PEI, into
      polyelectrolyte multilayers has been studied to further develop platforms for
      local gene delivery. Polyplex embedding in synthetic and naturally degradable
      architectures was efficient for transfection of human hepato-cellular carcinoma
      cells.

PMID- 16413495
TI  - Prediction of treatment outcome among patients with irritable bowel syndrome
      treated with group cognitive therapy.
AB  - Using a sample of over 125 patients with irritable bowel syndrome (IBS) who were
      treated with cognitive therapy administered in small groups, we sought to predict
      end of treatment and 3-month follow-up improvement in two changes indices of
      gastrointestinal (GI) symptoms (Pain/Discomfort Index which assessed change in
      abdominal pain, abdominal tenderness and bloating and Bowel Regularity Index
      which assessed change in diarrhea and constipation). We also sought to predict
      scores on IBS specific quality of life (QOL) and overall level of psychological
      distress using the Global Severity Index (GSI) of the Brief Symptom Inventory
      (BSI). Significant, but modest, levels of prediction were found for prediction of
      improvement in GI symptoms (4-15% of variance). Stronger significant prediction
      was obtained for the QOL and global psychological distress measure with R(2)'s
      ranging from 0.36 to 0.50. A wide variety of demographic, GI symptom,
      psychological status and psychiatric status variables entered the final
      prediction equations.

PMID- 16413496
TI  - Jagged1 protein enhances the differentiation of mesenchymal stem cells into
      cardiomyocytes.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes
      if an appropriate cellular environment is provided. Notch signals exchanged
      between neighboring cells through the Notch receptor can eventually dictate cell
      differentiation. In our study, we show that MSC differentiation into
      cardiomyocytes is dependent on the Notch signal. METHODS: We created a myocardial
      infarction model in rat by coronary ligation, administered direct intramyocardial
      injection of DAPI-labeled MSC immediately, and observed the differentiation of
      MSCs after 14 days by immunofluorescence staining against troponin T. We cultured
      MSCs and cardiomyocytes in four ways, respectively, in vitro. (1) MSCs cocultured
      with cardiomyocytes obtained from neonatal rat ventricles in a ratio of 1:10. (2)
      The two types of cells were cultured in two chambers separated by a semipermeable
      membrane as indirect coculture group. (3) Notch receptor-soluble jagged1 protein
      was added to indirect coculture group. (4) Both jagged1 protein and gamma
      secretase inhibitor-DAPT were added to indirect coculture group. Two weeks later,
      we observed the differentiation percentage, respectively, by immunofluorescence
      staining. RESULTS: We found the differentiation of MSCs which were close to
      cardiomyocytes in vivo. The differentiation percentage of the four cell culture
      group was 30.13+/-2.16%, 12.52+/-1.18%, 26.33+/-2.20%, and 13.08+/-1.15%.
      CONCLUSIONS: MSCs can differentiate into cardiomyocytes in vitro and in vivo if a
      cardiomyocyte microenvironment is provided. 2. Cell-to-cell interaction is very
      important for the differentiation of MSCs into cardiomyocytes. 3. Jagged1 protein
      can activate Notch signal and enhance the differentiation of MSC into
      cardiomyocyte, while the effect can be inhibited by DAPT.

PMID- 16413497
TI  - Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk
      in Chinese population.
AB  - OBJECTIVE: The aims of the present study were to assess whether the glutathione S
      transferase T1 (GSTT1), M1 (GSTM1), and NAD(P)H: quinone oxidoreductase 1 (NQO1)
      genotypes are associated with type 2 diabetes mellitus (T2 DM) and to ascertain
      whether the levels of blood lipids given exposure to diabetes are modified by the
      specific genetic polymorphisms of GSTT1, GSTM1, and NQO1. METHODS: This case
      control study was conducted on 200 subjects. The genotypes were determined using
      a polymerase chain reaction (PCR) and PCR-restriction fragment length
      polymorphism. RESULTS: The GSTT1-present genotype conferred a statistically
      significant 0.49-fold reduction in risk of T2 DM relative to the null genotype.
      Individuals with GSTT1-null or GSTM1-null genotype had higher levels of low
      density-lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a),
      respectively. There was no association between either GSTM1 or NQO1 polymorphism
      and risk of T2 DM. CONCLUSION: The present results suggest that the GSTT1 gene
      may contribute to the development of T2 DM and may be one of the candidate genes
      of T2 DM in Chinese population.

PMID- 16413498
TI  - A light-driven proton pump from Haloterrigena turkmenica: functional expression
      in Escherichia coli membrane and coupling with a H+ co-transporter.
AB  - A gene encoding putative retinal protein was cloned from Haloterrigena turkmenica
      (JCM9743). The deduced amino acid sequence was most closely related to that of
      deltarhodopsin, which functions as a light-driven H+ pump and was identified in a
      novel strain Haloterrigena sp. arg-4 (K. Ihara, T. Uemura, I. Katagiri, T.
      Kitajima-Ihara, Y. Sugiyama, Y. Kimura, Y. Mukohata, Evolution of the archaeal
      rhodopsins: Evolution rate changes by gene duplication and functional
      differentiation, J. Mol. Biol. 285 (1999) 163-174. GenBank Accession No.
      AB009620). Thus, we called the present protein H. turkmenica deltarhodopsin
      (HtdR) in this report. Differing from the Halobacterium salinarum
      bacteriorhodopsin (bR), functional expression of HtdR was achieved in Escherichia
      coli membrane with a high yield of 10-15 mg protein/L culture. The photocycle of
      purified HtdR was similar to that of bR. The photo-induced electrogenic proton
      pumping activity of HtdR was verified. We co-expressed both HtdR and EmrE, a
      proton-coupled multi-drug efflux transporter in E. coli, and the cells
      successfully extruded ethidium, a substrate of EmrE, on illumination.

PMID- 16413499
TI  - Potentiation of TLR4 signalling by plasmin activity.
AB  - The potential for proteases to regulate mammalian TLR signalling is
      controversial. We found that inhibition of extracellular serine proteases did not
      reduce activation of TLR4, but observed that the protease plasmin, an important
      fibrinolytic plasma enzyme that also exerts proinflammatory functions in
      monocytes, potentiated TLR2 and TLR4 signalling in RAW264.7 macrophages. Plasmin
      enhanced endogenous production of TNFalpha and activation of an NF-kappaB
      reporter plasmid. These actions were prevented by inhibition of its proteolytic
      activity and were not recapitulated by agonists of protease-activated receptors.
      These studies link fibrinolysis and TLR signalling, identifying further
      mechanisms potentially involved in activation of innate immunity.

PMID- 16413500
TI  - TNP-470 blockage of VEGF synthesis is dependent on MAPK/COX-2 signaling pathway
      in PDGF-BB-activated hepatic stellate cells.
AB  - Angiogenesis is a key pathogenic event in hepatic fibrogenesis, which is mediated
      by activated hepatic stellate cells (HSCs). TNP-470 is a known anti-angiogenic
      agent in cancer, and in this study, we investigated the regulatory mechanisms of
      TNP-470 blockage of vascular endothelial growth factor (VEGF) synthesis in
      activated HSCs. Primary HSCs were isolated from rat liver, cultured in vitro, and
      activated with platelet-derived growth factor-BB (PDGF-BB). After treatment with
      TNP-470, Nimesulide, PD98059, SB203580 or SP600125, activated HSCs were analyzed
      by immunoblotting, quantitative RT-PCR, and ELISA for mitogen-activated protein
      kinase (MAPK) family [ERKs, JNK, and p38], cyclooxygenase-2 (COX-2), and VEGF
      levels. Phosphorylation of p44/42 MAPK, which was followed by increased
      expressions of COX-2 and VEGF, was observed in PDGF-BB-activated HSCs; these
      events could be ameliorated by addition with TNP-470 in time- and dose-dependent
      manners. TNP-470 also inhibited the secretion of VEGF from activated HSCs into
      culture supernatant. Furthermore, TNP-470 blockage of VEGF production in
      activated HSCs could be nullified by exogenous inoculation with prostaglandin
      E(2). In summary, our findings suggest that TNP-470 exhibits the observed anti
      angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42
      MAPK pathway to inhibit VEGF production.

PMID- 16413501
TI  - Direct chitosan-mediated gene delivery to the rabbit knee joints in vitro and in
      vivo.
AB  - Chitosan vector system is expected to be useful for direct gene therapy for joint
      disease. This study first sought to confirm that foreign genes can be transferred
      to articular chondrocytes in primary culture. Next, chitosan-DNA nanoparticles
      containing IL-1Ra or IL-10 gene were injected directly into the knee joint
      cavities of osteoarthritis rabbits to clarify the in vivo transfer availability
      of the chitosan vectors. Clear expression of IL-1Ra was detected in the knee
      joint synovial fluid of the chitosan IL-1Ra-injected group. While no expression
      was detected in the chitosan IL-10-injected group, this demonstrates that the
      transfection efficiency of chitosan-DNA nanoparticles was closely related to the
      type of the gene product. A significant reduction was also noted in the severity
      of histologic cartilage lesions in the group that received the chitosan IL-1Ra
      injection. This avenue may therefore represent a promising future treatment for
      osteoarthritis.

PMID- 16413502
TI  - Rab4GTPase modulates CFTR function by impairing channel expression at plasma
      membrane.
AB  - Cystic fibrosis (CF), an autosomal recessive disorder, is caused by the
      disruption of biosynthesis or the function of a membrane cAMP-activated chloride
      channel, CFTR. CFTR regulatory mechanisms include recruitment of channel proteins
      to the cell surface from intracellular pools and by protein-protein interactions.
      Rab proteins are small GTPases involved in regulated trafficking controlling
      vesicle docking and fusion. Rab4 controls recycling events from endosome to the
      plasma membrane, fusion, and degradation. The colorectal cell line HT-29 natively
      expresses CFTR and responds to cAMP stimulation with an increase in CFTR-mediated
      currents. Rab4 over-expression in HT-29 cells inhibits both basal and cAMP
      stimulated CFTR-mediated currents. GTPase-deficient Rab4Q67L and GDP locked
      Rab4S22N both inhibit channel activity, which appears characteristically
      different. Active status of Rab4 was confirmed by GTP overlay assay, while its
      expression was verified by Western blotting. The pull-down and
      immunoprecipitation experiments suggest that Rab4 physically interacts with CFTR
      through protein-protein interaction. Biotinylation with cell impermeant NHS-Sulfo
      SS-Biotin implies that Rab4 impairs CFTR expression at cell surface. The enhanced
      cytosolic CFTR indicates that Rab4 expression restrains CFTR appearance at the
      cell membrane. The study suggests that Rab4 regulates the channel through
      multiple mechanisms that include protein-protein interaction, GTP/GDP exchange,
      and channel protein trafficking. We propose that Rab4 is a dynamic molecule with
      a significant role in CFTR function.

PMID- 16413503
TI  - Transcriptional regulation of the cartilage intermediate layer protein (CILP)
      gene.
AB  - Cartilage intermediate layer protein (CILP) is an extracellular matrix protein
      abundant in cartilaginous tissues. CILP is implicated in common musculoskeletal
      disorders, including osteoarthritis and lumbar disc disease. Regulation of the
      CILP gene is largely unknown, however. We have found that CILP mRNA expression is
      induced by TGF-beta1 and dependent upon signaling via TGF-beta receptors. TGF
      beta1 induction of CILP is mediated by Smad3, which acts directly through cis
      elements in the CILP promoter region. Pathways other than Smad3 also are involved
      in TGF-beta1 induction of CILP. These observations, together with the finding
      that CILP protein binds and inhibits TGF-beta1, suggest that CILP and TGF-beta1
      may form a functional feedback loop that controls chondrocyte metabolism.

PMID- 16413504
TI  - Drug-protein recognition processes investigated by NMR relaxation data. A study
      on corticosteroid-albumin interactions.
AB  - In this paper we investigated the interaction processes occurring at the protein
      solvent interface for prednisolone-albumin and prednisone-albumin systems, using
      an approach based on the analysis of proton selective relaxation rate
      enhancements of the ligand in the presence of the macromolecule. The contribution
      from the bound ligand fraction to the observed relaxation rate in relation to
      protein concentration allowed the calculation of the affinity index[A]L(T) and
      the normalized affinity index [AI(N)]L(T) which removes the effects of motional
      anisotropies and different proton densities, and isolates the contribution due to
      a decrease in the ligand dynamics caused by the binding with the protein. This
      approach allowed the comparison of the binding ability of prednisolone and
      prednisone towards albumin.

PMID- 16413506
TI  - Redefining penems.
AB  - The antimicrobial class of penems has the potential to address most of the
      relevant resistance issues associated with beta-lactam antibiotics because of
      their exceptionally broad spectrum of antibacterial activity and their intrinsic
      stability against hydrolytic attack by many beta-lactamases including ESBL and
      AmpC enzymes. The subclass of carbapenems covers the spectrum of hospital
      pathogens whereas the subclass of penems covers community pathogens. The only
      currently available penem, faropenem, has a low propensity for resistance
      development, beta-lactamase induction and selection of carbapenem-resistant
      Pseudomonas aeruginosa. This makes it attractive for the treatment of community
      acquired infections and for step-down or sequential therapy following carbapenem
      treatment without jeopardizing the activity of carbapenems or the entire beta
      lactam class in the hospital environment.

PMID- 16413505
TI  - Epidermal growth factor receptor inhibitor (PD168393) potentiates cytotoxic
      effects of paclitaxel against androgen-independent prostate cancer cells.
AB  - Recent data showed that epidermal growth factor receptor (EGFR) inhibitors, such
      as ZD1839, alone or in combination with chemotherapeutic agents for androgen
      independent prostate cancer (AIPC) did not produce promising results in clinical
      settings. More effective regimens involving novel stronger inhibitor of EGFR and
      better combinations are needed. The anti-tumor activity of PD168393, an
      irreversible EGFR inhibitor, with or without chemotherapeutic agents for the
      treatment of AIPC was investigated in vitro. In results, both the androgen
      independent cell lines PC-3 and DU145 expressed higher levels of EGFR than the
      androgen-dependent MDA PCa 2b and androgen-responsive LNCaP cells by Western
      blotting. DU145 was much more sensitive to PD168393 and ZD1839 than MDA PCa 2b.
      PD168393, but not ZD1839, significantly potentiated paclitaxel cytotoxicity
      against DU145 by MTT assay and median-effect analysis. The combination of
      PD168393 or ZD1839 with other cytotoxic agents including docetaxel and 5
      fluorouracil, however, was either additive or antagonistic. Compared to
      paclitaxel alone, PD168393 significantly enhanced paclitaxel-induced DNA
      fragmentation, sub-G1 fraction accumulation, mitochondrial membrane dysfunction,
      cytochrome C release, caspase-3 activation and eventually apoptosis. These
      molecular events were accompanied by Bad up-regulation, p53 and p21Waf1/Cip1
      induction, ERK1/2 inactivation and inhibition of EGFR phosphorylation in the
      presence of PD168393. These effects did not involve significant alteration in the
      Akt1/2 and STAT3 signaling pathway. In conclusion, the combination of paclitaxel
      and PD168393 produced a profound synergistic growth inhibition of AIPC cells.
      Combining PD168393 with paclitaxel may have clinical benefits and warrants
      further investigation.

PMID- 16413507
TI  - Activation time course of responses to illusory contours and salient region: a
      high-density electrical mapping comparison.
AB  - Until recently, early visual areas (V1/V2) were believed to respond mainly to
      illusory contours (ICs). At present, however, functional neuroimaging suggests
      that the human lateral occipital complex (LOC), a higher tier than V2, responds
      strongly to ICs and that IC-related activation in V1/V2 in fact might be driven
      by feedback input from the LOC. When Kanizsa-type ICs are modified by rounding
      the corners of the inducers and misaligning them slightly, the impression of an
      enclosed salient region (SR) remains, although ICs no longer are perceived.
      Stanley and Rubin (Stanley, D.A., Rubin, N., 2003. fMRI activation in response to
      illusory contours and salient regions in the human lateral occipital complex.
      Neuron, 37, 323-331) found that the LOC responded to SR, suggesting that the LOC
      subserves a rapid but crude region-based segmentation process preceding boundary
      completion in V1/V2. The present study compared the time course of cortical
      responses to ICs with those to SR using high-density (74-channel) event-related
      potentials (ERPs). Scalp mapping and statistical analysis indicated that shared
      negative modulation for ICs and SR was distributed bilaterally over the lateral
      occipital scalp at a latency of 70 to 180 ms. Slightly later, a weak negative
      modulation occurred with ICs but not SR at the occipital pole scalp from 170 to
      180 ms. Dipoles for early and late modulations were fitted optimally in the LOC
      and occipital pole, respectively. The present results suggested that IC-related
      cortical activation could be separated into region-based segmentation and
      subsequent boundary completion.

PMID- 16413508
TI  - Exercise differentially regulates synaptic proteins associated to the function of
      BDNF.
AB  - We explored the capacity of exercise to impact select events comprising synaptic
      transmission under the direction of brain-derived neurotrophic factor (BDNF),
      which may be central to the events by which exercise potentiates synaptic
      function. We used a specific immunoadhesin chimera (TrkB-IgG) that mimics the
      BDNF receptor, TrkB, to selectively block BDNF in the hippocampus during 3 days
      of voluntary wheel running. We measured resultant synapsin I, synaptophysin, and
      syntaxin levels involved in vesicular pool formation, endocytosis, and
      exocytosis, respectively. Synapsin I is involved in vesicle pool formation and
      neurotransmitter release, synaptophysin, in the biogenesis of synaptic vesicles
      and budding, and syntaxin, in vesicle docking and fusion. Exercise preferentially
      increased synapsin I and synaptophysin levels, without affecting syntaxin. There
      was a positive correlation between synapsin I and synaptophysin in exercising
      rats and synapsin I with the amount of exercise. Blocking BDNF abrogated the
      exercise-induced increases in synapsin I and synatophysin, revealing that
      exercise regulates select properties of synaptic transmission under the direction
      of BDNF.

PMID- 16413510
TI  - A firing rate model of Parkinsonian deficits in interval timing.
AB  - To account for deficits in interval timing observed in Parkinson's Disease (PD)
      patients, we develop a model based on the accumulating firing rate of a neural
      population with recurrent excitation. This model naturally produces the
      curvilinear accumulation of neural activity introduced to timing psychophysics by
      Miall (Models of Neural Timing, Elsevier Science, 1996), and implicated in
      Parkinsonian timing by Malapani and Rakitin (Functional and Neural Mechanisms of
      Interval Timing, CRC Press, 2003). The parameters essential for our model are the
      strength of the net neural feedback and the mean rate of inputs to the population
      from external brain areas. Systematic variations in these parameters reproduce
      the PD migration effect, in which estimates of long and short intervals drift
      towards each other, as well as uniform slowing of time estimates observed under
      other experimental conditions. For example, our model suggests that dopamine
      depletion in PD patients increases the neural feedback parameter and decreases
      the effective input parameter for populations involved in the production of time
      estimates. The model also explains why the migration effect will be associated
      with a violation of the scalar property, the linear increase in the standard
      deviation of time estimates with the duration of the target interval that is
      ubiquitous in healthy participants. We also show that the effect of
      systematically decreasing the input rate parameter in our model is equivalent to
      increasing thresholds, so that either of these changes may be associated with the
      Parkinsonian state.

PMID- 16413509
TI  - Adenosine A2A receptors are expressed by GABAergic neurons of medulla oblongata
      in developing rat.
AB  - During early development, adenosine contributes to the occurrence of respiratory
      depression and recurrent apneas. Recent physiological studies indicate that
      GABAergic mechanisms may be involved in this inhibitory action of adenosine, via
      their A(2A) receptors. In the present study, in situ hybridization with
      ribonucleotide probes for A(2A) receptor (A(2A)R) mRNA was combined with the
      immunolabeling technique for parvalbumin and transneuronal retrograde tracing
      method using green fluorescent protein expressing pseudorabies virus (GFP-PRV) to
      (1) characterize age-dependent changes in the expression of adenosine A(2A)Rs
      mRNA in brain stem regions where GABAergic neurons are located; (2) determine
      whether GABA-containing neurons express A(2A)R mRNA traits, and (3) identify
      whether bulbospinal GABAergic neurons projecting to phrenic nuclei contain A(2A)R
      mRNA. Results revealed expression of A(2A) receptors in regions of medulla
      oblongata containing GABAergic neurons, namely in the ventral aspect of the
      medulla, within the Botzinger region and caudal to it, the gigantocellular
      reticular nucleus, midline neurons and the caudal ventrolateral medulla
      oblongata. Furthermore, a subpopulation of identified GABAergic neurons,
      projecting to the phrenic motor nuclei, possess A(2A)R mRNA. It is concluded that
      adenosine A(2A)Rs expressed by GABAergic neurons are likely to play a role in
      mediating adenosine-induced respiratory depression.

PMID- 16413511
TI  - Modulation of the electrophysiological correlates of retrieval cue processing by
      the specificity of task demands.
AB  - Retrieval orientation refers to the differential processing of retrieval cues
      according to the type of information sought from memory (e.g., words vs.
      pictures). In the present study, event-related potentials (ERPs) were employed to
      investigate whether the neural correlates of differential retrieval orientations
      are sensitive to the specificity of the retrieval demands of the test task. In
      separate study-test phases, subjects encoded lists of intermixed words and
      pictures, and then undertook one of two retrieval tests, in both of which the
      retrieval cues were exclusively words. In the recognition test, subjects
      performed 'old/new' discriminations on the test items, and old items corresponded
      to only one class of studied material (words or pictures). In the exclusion test,
      old items corresponded to both classes of study material, and subjects were
      required to respond 'old' only to test items corresponding to a designated class
      of material. Thus, demands for retrieval specificity were greater in the
      exclusion test than during recognition. ERPs elicited by correctly classified new
      items in the two types of test were contrasted according to whether words or
      pictures were the sought-for material. Material-dependent ERP effects were
      evident in both tests, but the effects onset earlier and offset later in the
      exclusion test. The findings suggest that differential processing of retrieval
      cues, and hence the adoption of differential retrieval orientations, varies
      according to the specificity of the retrieval goal.

PMID- 16413512
TI  - Activation of the JAK-STAT signaling pathway in the rat basilar artery after
      subarachnoid hemorrhage.
AB  - The Janus kinase-signal transducer and activator of transcription (JAK-STAT) is
      one of the most important signaling pathways transducing signals from the cell
      surface in response to cytokines. Subarachnoid hemorrhage (SAH) produces
      cytokines in the CSF. We investigated whether this signaling pathway is activated
      in the rat basilar artery after SAH by cytokines. In a rat single-hemorrhage
      model of SAH, basilar arteries and CSF were obtained until 7 days after SAH. The
      concentration of interleukin-6 (IL-6) in CSF was measured by ELISA. Western blot
      analysis with JAK1, phosphospecific-JAK1, STAT3, phosphospecific STAT3 at Tyr705
      and Ser727, cyclooxygenase-2 (COX-2), and actin antibodies was performed in
      basilar artery. The expressions of STAT3, phosphospecific STAT3 at Tyr705 and
      Ser727, and COX-2 in basilar artery were examined by immunohistochemical studies.
      The concentration of IL-6 immediately increased after SAH and Western blot
      analysis revealed that JAK1 was phosphorylated within 2 h, accompanied by
      phosphorylation of STAT3 at Tyr705, extending to Ser727 at days 1-2.
      Immunohistochemistry revealed phosphorylation of STAT3 to occur in endothelial
      and smooth muscle cells of the basilar artery. In addition, intracisternal
      injection of IL-6 by itself significantly increased phosphorylation of STAT3 at
      Tyr705 and Ser727. Expression of COX-2 was also upregulated in endothelial cells
      of the basilar artery. These results indicate that SAH produces the
      proinflammatory cytokine IL-6 in the CSF, which activates the JAK-STAT signaling
      pathway in the basilar artery and induces transcription of immediate early genes.

PMID- 16413513
TI  - Neuroprotective effect of calcium channel blocker against retinal ganglion cell
      damage under hypoxia.
AB  - The purpose of this study was to determine whether iganidipine, nimodipine and
      lomerizine, potentially useful calcium channel blockers for ophthalmic treatment,
      have direct retinal neuroprotective effects against hypoxic damage in
      experimental in vitro model. We used purified retinal ganglion cells (RGCs) from
      newborn rats. RGCs were incubated in controlled-atmosphere incubator in which
      oxygen levels were reduced to 5% normal partial pressure and cell viability was
      assessed. We also examined the effect of calcium channel blockers on the calcium
      ion concentration in RGC under hypoxic stress by calcium imaging. Iganidipine,
      nimodipine and lomerizine (0.01-1 microM) increased the RGC viability. Increase
      in intra-RGC calcium ion concentration by hypoxic damage was reduced by these
      calcium channel blockers. In conclusion, iganidipine, nimodipine and lomerizine
      were effective against hypoxic RGC damage in vitro. This neuroprotective effect
      was thought to be mediated by blocking calcium ion influx into RGC. These
      findings suggest that iganidipine, nimodipine and lomerizine have a direct
      neuroprotective effect against RGC damage related to hypoxia.

PMID- 16413514
TI  - The role of perceptual load in visual awareness.
AB  - Does awareness depend on attention? This is a fundamental issue for understanding
      the relationship of attention and awareness, yet previous research provided mixed
      results. Here, I describe new research that shows that the effects of attention
      on awareness depend on the level of perceptual load in the attended task.
      Awareness reports in both the inattentional blindness and change blindness
      paradigms were found to depend on the extent to which an attended primary task
      loads attention. Neuroimaging results revealed the involvement of frontoparietal
      attention network in awareness and transcranial magnetic stimulation experiments
      confirmed a causal role for frontoparietal activity in awareness. These results
      clarify the role of attention and associated frontoparietal activity in visual
      awareness within the framework of load theory of attention.

PMID- 16413515
TI  - Studying ischemic preconditioning in isolated cardiomyocyte models.
AB  - Isolated cardiomyocytes, obtained by enzymatic digestion of whole hearts, have
      multiple advantages, most related to their accessibility to microscopic
      visualization, beyond the obvious elimination of other cell types that exist in
      the heart. Conversely, they cannot reproduce the mechanical disruption of
      reperfusion hypercontracture or the vascular phenomena of leukocyte plugging and
      compression from interstitial edema and contracture that can lead to the no
      reflow phenomenon. Nevertheless, ischemic preconditioning has been consistently
      demonstrated to be a potent protective mechanism in freshly isolated and cultured
      cardiomyocytes across multiple species, indicating that much of the innate
      protection of ischemic preconditioning resides in cardiomyocytes. Centrifuging
      freshly isolated cardiomyocytes into a pellet with only a thin layer of
      supernatant covered by oil has proven to be an excellent model of simulated
      ischemia. In culture, cardiomyocytes may be exposed to severe hypoxia only or to
      various protocols for simulated ischemia in which an acid/lactate-rich,
      hyperkalemic extracellular environment with substrate deprivation (lacking
      glucose) is typically added. Reperfusion is simulated by well-oxygenated media of
      normal ionic composition. Cardiomyocyte injury has been usually evaluated by cell
      membrane permeability to dyes, often under hypo-osmotic conditions (osmotic
      fragility) or enzyme release. A survey of the use of cardiomyocyte models to
      study preconditioning is presented with the emphasis on examples of the
      innovative measurements, increasingly involving molecular techniques, that point
      to an increasing future role for these models in preconditioning research and,
      more generally, in the mechanistic study of myocardial ischemia/reperfusion.

PMID- 16413516
TI  - Adenosine is a negative regulator of NF-kappaB and MAPK signaling in human
      intestinal epithelial cells.
AB  - Previous studies suggest that adenosine possesses anti-inflammatory properties,
      however, the mechanisms by which adenosine affects immune function remain
      unclear, particularly in the intestine. In this study, we hypothesized that
      adenosine directly affects pro-inflammatory gene expression in intestinal
      epithelial cells through modulation of NF-kappaB signaling. HT-29 cells were
      treated with adenosine prior to incubation with various stimuli and pro
      inflammatory gene expression and signal transduction analyzed. Adenosine
      pretreatment resulted in a reduction in IL-8 expression and secretion in response
      to TNF-alpha, IL-1, LPS, and PMA. This effect was paralleled by inhibition of
      kappaB-driven luciferase expression and a reduction in recruitment of NF-kappaB
      to the IL-8 promoter. Pretreatment of HT-29 cells also resulted in reduced ERK,
      p38, and JNK MAPK phosphorylation, following TNF-alpha treatment. The observed
      effects in this study occurred independently of known surface adenosine
      receptors. This study identifies adenosine as a potent negative regulator of pro
      inflammatory signaling in intestinal epithelial cells.

PMID- 16413518
TI  - Alkanes are not innocuous vehicles for hydrophobic reagents in membrane studies.
AB  - Alkanes (C6-C16) are often used as vehicles for hydrophobic reagents, e.g. long
      chain ceramides, in cell biology studies. It is generally understood that they
      are inert solvents, particularly when added in small volumes. However, simple
      calculations show that, under standard experimental conditions in cell studies,
      alkane: phospholipid molar ratios in excess of 1000:1 may be found. Even at much
      smaller ratios (close to 1:1) our studies with liposomes show that alkanes induce
      vesicle aggregation. Differential scanning calorimetry shows marked changes in
      both the gel-fluid and the lamellar-hexagonal transitions. Alkanes inhibit
      bacterial sphingomyelinase when acting on large unilamellar vesicles, and
      activate bacterial phospholipase C under the same conditions. Thus, the use of
      alkanes in cell studies requires strict control experiments to avoid artefactual
      results.

PMID- 16413517
TI  - Serum sphinganine and the sphinganine to sphingosine ratio as a biomarker of
      dietary fumonisins during chronic exposure in ducks.
AB  - Sphinganine concentration (Sa) and sphinganine to sphingosine ratio (Sa/So) are
      sensitive biomarkers of fumonisin B1 (FB1) exposure in animals and have been
      proposed to reveal FB1 exposure in humans. They correlate with liver and kidney
      toxicity and often precede signs of toxicity. However, the use of Sa and Sa/So is
      confusing during chronic exposure. Indeed, some authors report altered
      sphingolipids metabolism, whereas others fail to demonstrate significant effect.
      The aim of this study was to investigate the kinetics of Sa and Sa/So in the
      serum of ducks over a 77-day exposure to 0, 2, 8, 32 and 128 mg FB1/kg feeds.
      Serum biochemistry was also investigated to reveal hepatotoxicity. The results
      obtained indicate that the kinetics of sphingolipids and serum biochemistry are
      closely linked with the duration of the exposure. After a strong and rapid
      increase Sa and Sa/So decrease then stabilize. The lowest investigated dose able
      to determine a detectable effect is 2 mg/kg feeds, the Sa/So ratio being the most
      sensitive biomarker of FB1 exposure.

PMID- 16413519
TI  - The orientation effect of gramicidin A on bicelles and Eu3+ -doped bicelles as
      studied by solid-state NMR and FT-IR spectroscopy.
AB  - We have explored the effect of gramicidin A (gA) on bicelle (Bic) orientation in
      the absence and presence of Eu(3+) by (31)P and (2)H NMR at different DMPC/gA
      ratios. FT-IR spectroscopy was used to assess the lipid chain ordering and verify
      the transmembrane peptide conformation. Our results show a time-dependent
      flipping of the bilayer normal alignment at high temperatures and high proportion
      of gA. The results are explained by both the diamagnetic susceptibility
      anisotropy of the beta(6.3) helical peptides and viscosity of the lipid mixture.
      The concentration effect of gramicidin on Bic/Eu(3+) is compared to that on
      Eu(3+)-doped DMPC liposomes. The Bic/Eu(3+) system is no longer oriented in the
      presence of gA and adopts a vesicular morphology while the peptide incorporation
      induces the formation of ellipsoidal DMPC/Eu(3+) assemblies aligned with their
      normal parallel to the magnetic field. The difference is explained in terms of
      lipid chain disorder and size of the bilayers.

PMID- 16413520
TI  - The phase transition behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) model membrane influenced by 2,4-dichlorophenol--an FT-Raman spectroscopy
      study.
AB  - The effect of 2,4-dichlorophenol (DCP) on the structures and phase transitions of
      fully hydrated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes was
      studied using FT-Raman spectroscopy. Whereas the Raman frequency shifts of the
      most frequently investigated bands of C-C and C-H stretching regions only
      indicate the main phase transition (P(beta')-L(alpha)) of the pure DPPC/water
      system, the Raman shift of C-H scissoring vibration at 1440 cm(-1) was found to
      be able to reveal the pretransition (L(beta')-P(beta')) as well. Analyzing the
      spectral parameters of the trans band at 1128 cm(-1), which does not overlap with
      DCP vibrational modes, a continuous decrease of trans conformations was found
      with increasing DCP concentration at 26 degrees C accompanying the phase
      transitions L(beta')-P(beta') and P(beta')-L(alpha). The intensity ratio of the
      symmetrical and asymmetrical methylene stretching bands (at 2850 cm(-1) and 2880
      cm(-1)), defined as the disorder parameter by Levin [Levin, I.W., 1985. Two types
      of hydrocarbon chain interdigitation in sphingomielin bilayers. Biochemistry 24,
      6282-6286], indicated that in the interdigitated phase (L(I)) the order is
      markedly high and comparable with that of L(beta). Both the phase transition
      P(beta')-L(alpha) in the DCP/DPPC molar ratio range of 10/100-50/100 and the
      phase transition L(I)-L(alpha) led to a significant increase of disordered chains
      and the presence of DCP molecules induced a more disordered chain region than
      that observed in the L(alpha) phase of DPPC. Nevertheless, it was found that the
      L(alpha) phase with DCP contains approximately the same amount of trans
      conformers than that without DCP.

PMID- 16413521
TI  - Folic acid, inflammation, and atherosclerosis: false hopes or the need for better
      trials?
AB  - An increasing body of evidence supports the existence of a strong link between
      inflammation, endothelial dysfunction, and the onset and progression of
      atherosclerosis. However, a cause-effect relationship between these phenomena has
      not been demonstrated yet. Although some inflammatory markers, such as C-reactive
      protein, have been recently shown to improve risk stratification and to strongly
      predict cardiovascular outcome, it is largely unknown whether modifications of
      these markers might provide salutary effects and reduce cardiovascular morbidity
      and mortality. The B-vitamin folic acid has recently gained attention because of
      its potential to provide beneficial effects on surrogate end-points, such as
      endothelial function, in patients at high cardiovascular risk. However, the role
      of folic acid in mitigating the pro-inflammatory state associated with
      atherosclerosis is controversial. Despite the theoretical arguments supporting
      the potential anti-atherosclerotic and anti-inflammatory effects of folic acid,
      the current evidence is limited, deriving from small trials on different study
      populations, using folic acid often in combination with other vitamins and for
      different treatment periods. This review will consider the current evidence
      supporting the role of some well-established inflammatory markers in predicting
      cardiovascular outcomes, the mechanisms by which folic acid might exert anti
      inflammatory effects, the epidemiological data relating folic acid concentrations
      with inflammatory markers, the published interventional studies on the effects of
      folic acid supplementation on these markers, and the factors that need to be
      considered in designing future trials.

PMID- 16413522
TI  - Significance of coronary artery calcification score (CACS) for the detection of
      coronary artery disease (CAD) in chronic dialysis patients.
AB  - BACKGROUND: Coronary artery disease (CAD) is a principal cause of death in
      patients with end-stage renal disease (ESRD). The coronary artery calcification
      score (CACS), determined by electron-beam computed tomography (EBCT), is useful
      for the detection of CAD in non-ESRD patients. There are few reports on the
      usefulness of EBCT for the detection of CAD, however, in ESRD patients. We
      examined the relation between CACS and CAD in ESRD patients. METHODS: Coronary
      angiography (CAG) was used to diagnose CAD in patients with significant coronary
      artery stenosis (>or=50%). We examined 76 ESRD patients on chronic dialysis
      therapy from 1997 to 2005, of which 51 are men, 25 are women, mean (S.D.) age of
      57.9 (12.1) years and mean (S.D.) HD duration of 7.7 (6.6) years. There were 50
      (35 men, 15 women) patients with CAD and 26 (16 men, 10 women) without CAD.
      RESULTS: The median CACS was 1290 in all patients, 1689 in the CAD group and 527
      in the non-CAD group; the mean (S.D.) CACS was 1833 (2003) in all patients, 2338
      (2209) in the CAD group and 861 (991) in the non-CAD group. CACS was
      significantly higher in the CAD group than in the non-CAD group. The CACS cutoff
      values for predicting CAD were calculated at intervals of 100. At the cutoff
      values of >or=100, >or=500, >or=1000, >or=2000, and >or=3000, the sensitivity was
      98%, 90%, 68%, 42%, and 32% and the specificity was 35%, 50%, 69%, 85%, and 96%,
      respectively. CONCLUSIONS: EBCT is not adequate for screening asymptomatic ESRD
      patients. Because EBCT is less invasive than CAG, further study is necessary to
      determine whether CAG should be performed in all high-risk ESRD patients on
      chronic dialysis.

PMID- 16413523
TI  - Assay of DNA-binding proteins with a dsDNA-coupled plate.
AB  - OBJECTIVES: This paper fabricated a cost-effective dsDNA-coupled plate (dcPlate)
      and applied it to measure the abundance and DNA-binding activity of a DNA-binding
      protein (DBP). DESIGN AND METHODS: The dcPlate was manufactured by covalently
      immobilizing an amino-modified oligonucleotide in wells of the plate coated with
      N-oxysuccinimide esters. The dcPlate was applied to measure the abundance of DNA
      binding activity of a DBP in the same four steps, including protein incubation,
      primary antibody binding, enzyme-linked secondary antibody binding, and
      colorimetric development. RESULTS: The detections of three purified DBPs
      including NF-kappaB, AP1 and SP1, and HeLa cell nuclear extract and assays of DNA
      binding activity of NF-kappaB p50 to five various DNA sequences demonstrated that
      dcPlate can be used to measure the abundance of DBPs quantitatively and assay DNA
      binding activity of DBPs in high throughputs format. CONCLUSIONS: The homemade
      cost-effective dcPlate provides a simple and versatile platform for studying
      DBPs.

PMID- 16413525
TI  - Modulation of the Suppressor of fused protein regulates the Hedgehog signaling
      pathway in Drosophila embryo and imaginal discs.
AB  - The Suppressor of fused (Su(fu)) protein is known to be a negative regulator of
      Hedgehog (Hh) signal transduction in Drosophila imaginal discs and embryonic
      development. It is antagonized by the kinase Fused (Fu) since Su(fu) null
      mutations fully suppress the lack of Fu kinase activity. In this study, we
      overexpressed the Su(fu) gene in imaginal discs and observed opposing effects
      depending on the position of the cells, namely a repression of Hh target genes in
      cells receiving Hh and their ectopic expression in cells not receiving Hh. These
      effects were all enhanced in a fu mutant context and were suppressed by cubitus
      interruptus (Ci) overexpression. We also show that the Su(fu) protein is poly
      phosphorylated during embryonic development and these phosphorylation events are
      altered in fu mutants. This study thus reveals an unexpected role for Su(fu) as
      an activator of Hh target gene expression in absence of Hh signal. Both negative
      and positive roles of Su(fu) are antagonized by Fused. Based on these results, we
      propose a model in which Su(fu) protein levels and isoforms are crucial for the
      modulation of the different Ci states that control Hh target gene expression.

PMID- 16413526
TI  - The hedgehog-related gene wrt-5 is essential for hypodermal development in
      Caenorhabditis elegans.
AB  - The Caenorhabditis elegans genome encodes a series of hedgehog-related genes,
      which are thought to have evolved and diverged from an ancestral Hh gene. They
      are classified into several families based on their N-terminal domains. Here, we
      analyze the expression and function of a member of the warthog gene family, wrt
      5, that lacks the Hint/Hog domain. wrt-5 is expressed in seam cells, the pharynx,
      pharyngeal-intestinal valve cells, neurons, neuronal support cells, the excretory
      cell, and the reproductive system. WRT-5 protein is secreted into the
      extracellular space during embryogenesis. Furthermore, during larval development,
      WRT-5 protein is secreted into the pharyngeal lumen and the pharyngeal expression
      changes in a cyclical manner in phase with the molting cycle. Deletion mutations
      in wrt-5 cause embryonic lethality, which are temperature sensitive and more
      severe at 15 degrees C than at 25 degrees C. Animals that hatch exhibit variable
      abnormal morphology, for example, bagging worms, blistering, molting defects, or
      Roller phenotypes. We examined hypodermal cell junctions using the AJM-1Colon,
      two colonsGFP marker in the wrt-5 mutant background and observed cell boundary
      abnormalities in the arrested embryos. AJM-1Colon, two colonsGFP protein is also
      misplaced in pharyngeal muscle cells in the absence of WRT-5. In conclusion, we
      show that wrt-5 is an essential gene that - despite its lack of a Hint domain -
      has multiple functions in C. elegans and is implicated in cell shape integrity.

PMID- 16413524
TI  - Differential expression of espin isoforms during epithelial morphogenesis,
      stereociliogenesis and postnatal maturation in the developing inner ear.
AB  - The espins are a family of multifunctional actin cytoskeletal proteins. They are
      present in hair cell stereocilia and are the target of mutations that cause
      deafness and vestibular dysfunction. Here, we demonstrate that the different
      espin isoforms are expressed in complex spatiotemporal patterns during inner ear
      development. Espin 3 isoforms were prevalent in the epithelium of the otic pit,
      otocyst and membranous labyrinth as they underwent morphogenesis. This espin was
      down-regulated ahead of hair cell differentiation and during neuroblast
      delamination. Espin also accumulated in the epithelium of branchial clefts and
      pharyngeal pouches and during branching morphogenesis in other embryonic
      epithelial tissues, suggesting general roles for espins in epithelial
      morphogenesis. Espin reappeared later in inner ear development in differentiating
      hair cells. Its levels and compartmentalization to stereocilia increased during
      the formation and maturation of stereociliary bundles. Late in embryonic
      development, espin was also present in a tail-like process that emanated from the
      hair cell base. Increases in the levels of espin 1 and espin 4 isoforms
      correlated with stereocilium elongation and maturation in the vestibular system
      and cochlea, respectively. Our results suggest that the different espin isoforms
      play specific roles in actin cytoskeletal regulation during epithelial
      morphogenesis and hair cell differentiation.

PMID- 16413527
TI  - Direct evidence that ventral forebrain cells migrate to the cortex and contribute
      to the generation of cortical myelinating oligodendrocytes.
AB  - Cortical neuroepithelial cells generate neurons, astrocytes, and oligodendrocytes
      (OLs) in vitro. However, whether cortical OLs are derived from the cortical
      neuroepithelium or migrate from the ventral forebrain is under severe debate yet.
      This is due to the fact that OL progenitor cells (OPCs), as marked by the
      expression of PDGFRalpha or NG2, are generated at around embryonic day (E) 11 or
      12 in the mouse ganglionic eminences, but the myelinating OLs appear during the
      second week postnatally in the cortex. There has been no labeling method for long
      term glial cell-lineage tracing. Thus, we developed a new strategy: plasmid DNA
      encoding Cre recombinase was introduced into the Cre/loxP reporter forebrain in
      ventral- or dorsal-specific manner by in utero DNA electroporation. The reporter
      gfp gene is expressed permanently owing to the chromosomal DNA recombination. The
      GFP-labeled myelinating OLs were detected in the adult cortex when
      electroporation was targeted to the ventral neuroepithelium, demonstrating at
      least some of the myelinating OLs are derived from the ventral forebrain.
      However, when electroporation was targeted to the dorsal, we could not find GFP
      labeled myelinating OLs. This suggests that the progenitors of cortical OPCs are
      absent or located at restricted regions in the dorsal forebrain (cortex) at E12.

PMID- 16413528
TI  - Epimorphin acts extracellularly to promote cell sorting and aggregation during
      the condensation of vertebral cartilage.
AB  - Formation of vertebrae occurs via endochondral ossification, a process involving
      condensation of precartilaginous cells. Here, we provide the first molecular
      evidence of mechanism that underlies initiation of this process by showing that
      the extracellular factor, Epimorphin, plays a role during early steps in
      vertebral cartilage condensation. Epimorphin mRNA is predominantly localized in
      the vertebral primordium. When provided exogenously in ovo, it causes precocious
      differentiation of chondrocytes, resulting in the formation of supernumerary
      vertebral cartilage in chicken embryos. To further analyze its mode of action, we
      used an in vitro co-culture system in which labeled 10T1/2 or sclerotomal
      prechondrogenic cells were co-cultured with unlabeled Epimorphin-producing cells.
      In the presence of Epimorphin, the labeled cells formed tightly packed
      aggregates, and sclerotomal cells displayed augmented accumulation of NCAM and
      other early markers of chondrocyte differentiation. Finally, we found that the
      Epimorphin expression is initiated during vertebrogenesis by Sonic hedgehog from
      the notochord mediated by Sox 9. We present a model in which successive action of
      Epimorphin in recruiting and stacking sclerotomal cells leads to a sequential
      elongation of a vertebral primordium.

PMID- 16413529
TI  - Regulation of the Drosophila transcription factor, Cubitus interruptus, by two
      conserved domains.
AB  - Hedgehog signaling is required for the development of many organisms, including
      Drosophila. In flies, Hh patterns the embryonic epidermis and larval imaginal
      discs by regulating the transcription factor, Cubitus interruptus (Ci). To date,
      three levels of regulation have been identified: proteolytic processing into a
      repressor, nuclear import, and activation. In this report, we characterize the
      function of two Ci domains that are conserved in the vertebrate homologues, GLI1,
      GLI2, and GLI3. One domain includes the first two of five C(2)-H(2) zinc-fingers.
      While conserved in all members of the GLI/Ci family, the first two fingers do not
      appear to make significant contacts with the DNA target sequence. Ci protein
      lacking this region is still able to interact with the cytoplasmic complex and
      activate transcription in embryos and wing imaginal discs, but it is no longer
      processed into the repressor form. The second domain, termed NR for "N-terminal
      Regulatory", binds Suppressor of Fused. Deletion of this region has little effect
      on embryonic patterning, but compromises cytoplasmic retention of Ci. Analysis of
      the amino acid sequence of this domain identifies 11 perfectly conserved serines
      and one tyrosine. We propose that this region may be modified, possibly by
      phosphorylation, to regulate Ci nuclear import.

PMID- 16413530
TI  - The Sm proteins regulate germ cell specification during early C. elegans
      embryogenesis.
AB  - Sm and Sm-like proteins are core components of the splicesome but have other
      functions distinct from pre-mRNA processing. Here, we show that Sm proteins also
      regulate germ cell specification during early C. elegans embryogenesis. SmE and
      SmG were required to maintain transcriptional quiescence in embryonic germ cell
      precursors. In addition, depletion of SmE inhibited expression of the germ
      lineage-specific proteins PIE-1, GLD-1, and NOS-2, but did not affect maintenance
      of several maternal mRNAs. PIE-1 had previously been shown to activate
      transcriptional silencing and NOS-2 expression. We found that PIE-1 also promotes
      GLD-1 expression by a process that is independent of transcriptional silencing.
      Thus, Sm proteins could control transcriptional silencing and maternal protein
      expression by regulating PIE-1. However, loss of SmE function also caused defects
      in P granule localization and premature division in early germline blastomeres,
      processes that are independent of PIE-1 function. Therefore, the Sm proteins
      control multiple aspects of germ cell precursor development. Because depletion of
      several other core splicing factors did not affect these events, these Sm
      functions are likely distinct from pre-mRNA splicing. Sm family proteins assemble
      into ribonucleoprotein complexes (RNPs) that control RNA activities. We suggest
      that novel Sm RNPs directly or indirectly influence posttranscriptional control
      of maternal mRNAs to promote germ cell specification in the early C. elegans
      embryo.

PMID- 16413531
TI  - Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of
      MRL/MpJ-lpr/lpr mice.
AB  - T cell immune responses play important roles in the pathogenesis of systemic
      lupus erythematosus (SLE). (S)-Armepavine (C19H23O3N; MW313) from Nelumbo
      nucifera suppresses T cells proliferation. To study its potential benefit on SLE,
      we examined effects of (S)-armepavine on MRL/MpJ-lpr/lpr mice, which have similar
      disease features to human SLE. MRL/MpJ-lpr/lpr mice were treated orally with (S)
      armepavine for 6 weeks and their SLE characteristics were evaluated. The results
      revealed that (S)-armepavine prevented lymphadenopathy and elongated life span of
      MRL/MpJ-lpr/lpr mice. It seemed to be mediated by inhibition of splenocytes
      proliferation, suppression of interleukin-2 (IL-2), interleukin-4, interleukin
      10, and interferon-gamma (IFN-gamma) gene expressions, reduction of glomerular
      hypercellularity and immune complexes deposition, and decrease of urinary protein
      and anti-double stranded DNA autoantibody production. Furthermore, the data
      demonstrated (S)-armepavine impaired IL-2 and IFN-gamma transcripts in human
      peripheral blood mononuclear cells. We suggest that (S)-armepavine may be an
      immunomodulator for the management of autoimmune diseases like SLE.

PMID- 16413533
TI  - Identification of anxiolytic ingredients in ginseng root using the elevated plus
      maze test in mice.
AB  - Ginseng root has been widely used for the management of anxiety and emotional
      instability, but there is little experimental evidence supporting these clinical
      applications. We pharmacologically identified the anxiolytic components in
      ginseng root, using the elevated plus-maze test. Male ICR albino mice and the
      following drugs were used: diazepam (0.5, 1 and 1.5 mg/kg, p.o.); red ginseng
      powder (300, 600 and 1200 mg/kg, p.o.); crude saponin and non-saponin ginseng
      fractions (50, 100 and 200 mg/kg, i.p., for each preparation); and pure
      ginsenoside Rb1, Rg1, and Ro (2.5, 5 and 10 mg/kg, i.p., for each preparation).
      Ginseng powder and crude saponin ginseng fraction significantly increased the
      frequency and duration of open arm entries. Among the three types of pure
      ginsenoside, only ginsenoside Rb1 significantly increased both the frequency and
      duration of open arm entries. Our results clearly indicate that ginsenoside Rb1
      is one of the active anxiolytic components of ginseng root.

PMID- 16413532
TI  - Effects of intravenous anesthetics on the activity of glutamate transporter EAAT3
      expressed in Xenopus oocytes: evidence for protein kinase C involvement.
AB  - We investigated the effects of the intravenous anesthetics, thiopental, etomidate
      and ketamine, on the activity of one type of glutamate transporters, EAAT3
      (excitatory amino acid transporter type 3). Rat EAAT3 was expressed in Xenopus
      oocytes by injection of its mRNA. Using two-electrode voltage clamp, membrane
      currents were recorded after the application of L-glutamate (30 microM) in the
      presence or absence of various concentrations of the anesthetics. Thiopental (0.3
      30 microM) and ketamine (3-1000 microM) did not affect EAAT3 activity. Etomidate
      decreased EAAT3 activity in a concentration-dependent manner (0.10-10 microM).
      Etomidate at 1 microM significantly decreased the Vmax, but not the Km of EAAT3
      for glutamate. Chelerythrine, a protein kinase C (PKC) inhibitor, significantly
      decreased EAAT3 activity, however, there were no statistical differences among
      the chelerythrine, etomidate or chelerythrine plus etomidate groups. Likewise,
      the combination of staurosporine, another PKC inhibitor, and etomidate did not
      decrease the responses further compared with staurosporine or etomidate alone.
      Phorbol-12-myrisate-13-acetate, a PKC activator, abolished etomidate-induced
      decrease in EAAT3 activity. Since our results showed that thiopental and ketamine
      did not affect EAAT3 activity significantly, EAAT3 may not be a target for their
      anesthetic effects. Our results also suggest that etomidate, possibly via PKC,
      decreased EAAT3 activity at clinically relevant concentrations.

PMID- 16413534
TI  - Mallory body forming cells express the preneoplastic hepatocyte phenotype.
AB  - The livers of mice fed diethyl 1,4-dihydro-2,4,6,-trimethyl-3,5
      pyridinedicarboxylate (DDC) for 10 weeks formed Mallory bodies (MBs) in clusters
      of hepatocytes. Mice withdrawn from DDC for 9 months developed liver tumors. In
      the present study, the phenotype of the hepatocytes that formed MBs and tumors
      was characterized. Immunoperoxidase and immunofluorescent stains were done on the
      DDC-treated mouse livers, as well as mouse liver tumors and a human
      hepatocellular carcinoma that formed MBs. Antibodies to markers of hepatocellular
      neoplasms such as alpha-fetoprotein (AFP), ubiquitin B (UbB) fatty acid synthase
      (FAS) and alpha2 macroglobulin (A2m) stained the MB forming cells positive.
      Quantitative real-time RT-PCR assay was used to measure AFP, UbB, FAS and GCP-3
      A2m mRNA levels in the livers of DDC fed mice and the DDC-induced mouse liver
      tumors. The FAS, UbB, GPC-3 and AFP mRNA levels were significantly increased in
      the MB forming liver cells. The in vitro model of MB formation was used to
      correlate MB formation with gene and protein expression. Primary cultures of DDC
      primed hepatocytes were compared with the controls. A2m and UbB expression
      increased in the primary cultures of DDC-primed hepatocytes when MBs formed.
      Thus, the tumor markers used to identify hepatocellular carcinoma were
      upregulated in cells forming MBs in vivo and in vitro, suggesting that MB forming
      cells express preneoplastic phenotypic features.

PMID- 16413535
TI  - Anti-P-selectin lectin-EGF domain monoclonal antibody inhibits the maturation of
      human immature dendritic cells.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells with the ability
      to initiate primary T cell responses. While it is well known that inflammatory
      stimuli induce the functional maturation of immature DCs, whether adhesion
      molecule selectins regulate DC maturation is poorly understood. Using anti-P
      selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the
      adhesion of P-, E-, and L-selectin, we demonstrate herein that selectins play
      important role in stimulating functional maturation of immature DCs. Immature DCs
      are generated from human cord blood CD34+ hematopoietic stem/progenitor cells
      that were cultured in the presence of stem cell factor, Fms-like tyrosine-kinase
      3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth
      factor-beta1. When stimulated with tumor necrosis factor-alpha (TNF-alpha),
      immature DCs differentiated into mature DCs, producing increased levels of
      costimulatory molecules and interleukin (IL)-12 and obtaining the ability to
      potently activate naive T cells. Interestingly, in contrast to mature DCs derived
      from TNF-alpha-induced immature DC cultures without PsL-EGFmAb, immature DCs
      treated with PsL-EGFmAb for 7 days were completely blocked their maturation, as
      evidenced by decreased expression of costimulatory molecules CD80, CD86, and
      CD83, inhibited production of IL-12, and inability to activate naive T cells in
      vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to be a valuable
      tool for the study of the molecular mechanisms of DC maturation, as well as for
      the prevention and treatment of DC-mediated autoimmunity.

PMID- 16413536
TI  - mtDNA controls expression of the Death Associated Protein 3.
AB  - The Death Associated Protein 3 (DAP3), a GTP-binding constituent of the small
      subunit of the mitochondrial ribosome, is implicated in the TNFalpha and IFNgamma
      apoptotic pathways of the cell and is involved in the maintenance of the
      mitochondrial network. We have investigated the mitochondrial role of DAP3 by
      analyzing its mRNA and protein expression in transformed and non-transformed cell
      lines presenting various levels of mtDNA. The 3 mtDNA-less (rho degrees ) cell
      lines showed a complete absence of DAP3, whereas the mRNA expression was
      conserved. In HepG2 cells treated with increasing doses of ddCTP, the depletion
      of mtDNA was accompanied by the reduced expression of DAP3. However, the
      expression of the corresponding mRNA was maintained, suggesting the existence of
      a post-transcriptional mechanism responsible for the depletion of the DAP3.
      Compared to the parental cells, the 3 rho degrees cell lines displayed partial
      resistance to staurosporin-induced cell death. The absence of pro-apoptotic DAP3
      in these mtDNA-less cells could explain their reduced apoptotic capacity. Our
      results suggest that the mtDNA content plays a role in cell apoptosis by
      mediating the expression of DAP3.

PMID- 16413537
TI  - Peroxisomal ABC transporters.
AB  - Peroxisomes perform a range of different functions, dependent upon organism,
      tissue type, developmental stage or environmental conditions, many of which are
      connected with lipid metabolism. This review summarises recent research on ATP
      binding cassette (ABC) transporters of the peroxisomal membrane (ABC subfamily D)
      and their roles in plants, fungi and animals. Analysis of mutants has revealed
      that peroxisomal ABC transporters play key roles in specific metabolic and
      developmental functions in different organisms. A common function is import of
      substrates for beta-oxidation but much remains to be determined concerning
      transport substrates and mechanisms which appear to differ significantly between
      phyla.

PMID- 16413540
TI  - Arachidonic acid induces specific membrane permeability increase in heart
      mitochondria.
AB  - Micromolar concentrations of arachidonic acid cause in Ca2+ loaded heart
      mitochondria matrix swelling and Ca2+ release. These effects appear to be
      unrelated to the classical membrane permeability transition (MPT), as they are
      CsA insensitive, membrane potential independent and can also be activated by
      Sr2+. Atractyloside potentiated and ATP inhibited the arachidonic acid induced
      swelling. These observations suggest that the ATP/ADP translocator (ANT) may be
      involved in the AA induced, CsA insensitive membrane permeability increase. Under
      the same experimental conditions used for heart mitochondria, arachidonic acid
      induced the classical CsA sensitive, ADP inhibitable MPT in liver mitochondria.

PMID- 16413539
TI  - The effect of 2',4',7-trihydroxyisoflavone on ultraviolet-induced matrix
      metalloproteinases-1 expression in human skin fibroblasts.
AB  - UV-induced matrix metalloproteinases (MMPs) cause connective tissue damage and
      the skin to become wrinkled and aged. Here, we investigated the effect of 2',4',7
      trihydroxyisoflavone (THF) on UV-induced MMP-1 expression in human skin
      fibroblasts (HSFs). We found that UV irradiation increases MMP-1 expression and
      that this is mediated by ERK and JNK activation, but not by p38 activation.
      Pretreatment of HSFs with 2',4',7-THF inhibited UV-induced MMP-1 expression in a
      dose-dependent manner, and also inhibited the UV-induced activations of ERK and
      JNK by inhibiting MEK1 and SEK1 activation, respectively. Moreover, inhibitions
      of ERK and JNK by 2',4',7-THF resulted in the decrease of c-Fos expression and c
      Jun phosphorylation/expression induced by UV, respectively, which led to the
      inhibition of UV-induced AP-1 DNA binding activity. This inhibitory effect of
      2',4',7-THF on MMP-1 was not mediated by an antioxidant effect. In conclusion,
      our results demonstrate that 2',4',7-THF can inhibit UV-induced MMP-1 expression
      by inhibiting the MEK1/ERK/c-Fos and SEK1/JNK/c-Jun pathways. Therefore, 2',4',7
      THF is a potential agent for the prevention and treatment of skin aging.

PMID- 16413538
TI  - Interferon regulatory factor-1 is prerequisite to the constitutive expression and
      IFN-gamma-induced upregulation of B7-H1 (CD274).
AB  - Majority of cancer cells upregulate co-inhibitory molecule B7-H1 which confers
      resistance to anti-tumor immunity, allowing cancers to escape from host immune
      surveillance. We addressed the molecular mechanism underlying the regulation of
      cancer-associated B7-H1 expression in response to interferon-gamma (IFN-gamma).
      Using promoter constructs in luciferase assay, the region between 202 and 320 bp
      from the translational start site is responsible for B7-H1 expression.
      Electrophoretic mobility shift assay, site-directed mutagenesis and knockdown
      experiment using siRNA revealed that interferon regulatory factor-1 (IRF-1) is
      primarily responsible for the constitutive B7-H1 expression as well as for the
      IFN-gamma-mediated B7-H1 upregulation in a human lung cancer cell line A549.
      Additionally, AG490, a Janus activated kinase/signal transducer and activator of
      transcription inhibitor, greatly abolished the responsiveness of A549 cells to
      IFN-gamma by reducing the IRF-1 transcription. Our findings support a critical
      role of IRF-1 in the regulation of constitutive and IFN-gamma-induced expression
      of B7-H1 in cancer cells.

PMID- 16413541
TI  - Energetics of RNA binding by the West Nile virus RNA triphosphatase.
AB  - The West Nile virus (WNV) RNA genome harbors the characteristic methylated cap
      structure present at the 5' end of eukaryotic mRNAs. In the present study, we
      report a detailed study of the binding energetics and thermodynamic parameters
      involved in the interaction between RNA and the WNV RNA triphosphatase, an enzyme
      involved in the synthesis of the RNA cap structure. Fluorescence spectroscopy
      assays revealed that the initial interaction between RNA and the enzyme is
      characterized by a high enthalpy of association and that the minimal RNA binding
      site of NS3 is 13 nucleotides. In order to provide insight into the relationship
      between the enzyme structure and RNA binding, we also correlated the effect of
      RNA binding on protein structure using both circular dichroism and denaturation
      studies as structural indicators. Our data indicate that the protein undergoes
      structural modifications upon RNA binding, although the interaction does not
      significantly modify the stability of the protein.

PMID- 16413542
TI  - Extracellular adenine nucleotides inhibit the release of major monocyte
      recruiters by human monocyte-derived dendritic cells.
AB  - Extracellular ATP is known to affect the maturation of monocyte-derived dendritic
      cells mainly by regulation of cytokines and costimulatory molecules. The present
      study describes the inhibition of MCP-1 (CCL2) and MIP-1alpha (CCL3) release by
      human monocyte-derived dendritic cells in response to adenine nucleotides. Our
      pharmacological data support the involvement of P2Y11 and P2Y1 purinergic
      receptors in the downregulation of these major monocyte recruiters. Migration
      assays have demonstrated that supernatants of dendritic cells treated with
      adenine nucleotides or anti-MCP-1/MIP-1alpha blocking antibodies display a
      strongly reduced capacity to attract monocytes and immature dendritic cells.

PMID- 16413543
TI  - Solution structure and dynamics of human metallothionein-3 (MT-3).
AB  - Alzheimer's disease is characterized by progressive loss of neurons accompanied
      by the formation of intraneural neurofibrillary tangles and extracellular amyloid
      plaques. Human neuronal growth inhibitory factor, classified as metallothionein-3
      (MT-3), was found to be related to the neurotrophic activity promoting cortical
      neuron survival and dendrite outgrowth in the cell culture studies. We have
      determined the solution structure of the alpha-domain of human MT-3 (residues 32
      68) by multinuclear and multidimensional NMR spectroscopy in combination with the
      molecular dynamic simulated annealing approach. The human MT-3 shows two metal
      thiolate clusters, one in the N-terminus (beta-domain) and one in the C-terminus
      (alpha-domain). The overall fold of the alpha-domain is similar to that of mouse
      MT-3. However, human MT-3 has a longer loop in the acidic hexapeptide insertion
      than that of mouse MT-3. Surprisingly, the backbone dynamics of the protein
      revealed that the beta-domain exhibits similar internal motion to the alpha
      domain, although the N-terminal residues are more flexible. Our results may
      provide useful information for understanding the structure-function relationship
      of human MT-3.

PMID- 16413544
TI  - Induction of apoptosis by p110C requires mitochondrial translocation of the
      proapoptotic BCL-2 family member BAD.
AB  - p110C, a 50-kDa isoform of the PITSLRE kinase family, was demonstrated to play an
      important role in cell apoptosis. However, how p110C exactly promotes apoptosis
      is unclear. Our previous study showed that p110C interacted with p21-activated
      kinase 1 (PAK1), an important kinase of the proapoptotic BCL-2 family member BAD,
      and evidently inhibited its kinase activity. Here, we report that overexpression
      of p110C leads to decreased phosphorylation of BAD and its subsequent
      translocation from cytosol to mitochondria, which in turn induces the release of
      cytochrome c and the onset of apoptosis. Knocking down endogenous BAD expression
      will inhibit p110C induced apoptosis. Two kinase dead forms of p110C, D149N and
      K36N, lose the ability to inhibit the kinase activity of PAK1 and fail to induce
      the translocation of BAD and the BAD and such proapoptotic ability is associated
      with the kinase activity of p110C.

PMID- 16413545
TI  - The influence of the signal dynamics of activated form of IKK on NF-kappaB and
      anti-apoptotic gene expressions: a systems biology approach.
AB  - NF-kappaB activation plays a crucial role in anti-apoptotic responses in response
      to the apoptotic signaling during tumor necrosis factor (TNF)-alpha stimulation.
      TNF-alpha induces apoptosis sensitive to the hepatitis B virus (HBV) infected
      cells, despite sustained NF-kappaB activation. Our results indicate that the HBV
      infection induces sustained NF-kappaB activation, in a manner similar to the TNF
      alpha stimulation. However, these effects are not merely combined. Computational
      simulations show that the level of form of the IKK complex activated by
      phosphorylation (IKK-p) affects the dynamic pattern of NF-kappaB activation
      during TNF-alpha stimulation in the following ways: (i) the initial level of IKK
      p determines the incremental change in IKK-p at the same level of TNF-alpha
      stimulation, (ii) the incremental change in IKK-p determines the amplitudes of
      active NF-kappaB oscillation, and (iii) the steady state level of IKK-p after the
      incremental change determines the period of active NF-kappaB oscillation. Based
      on experiments, we observed that the initial level of IKK-p was upregulated and
      the active NF-kappaB oscillation showed smaller amplitudes for a shorter period
      in HepG2.2.15 cells (HBV-producing cells) during TNF-alpha stimulation, as was
      indicated by the computational simulations. Furthermore, we found that during TNF
      alpha stimulation, NF-kappaB-regulated anti-apoptotic genes were upregulated in
      HepG2 cells but were downregulated in HepG2.2.15 cells. Based on the previously
      mentioned results, we can conclude that the IKK-p-level changes induced by HBV
      infection modulate the dynamic pattern of active NF-kappaB and thereby could
      affect NF-kappaB-regulated anti-apoptotic gene expressions. Finally, we postulate
      that the sensitive apoptotic response of HBV-infected cells to TNF-alpha
      stimulation is governed by the dynamic patterns of active NF-kappaB based on IKK
      p level changes.

PMID- 16413546
TI  - Genomics of plant ABC transporters: the alphabet of photosynthetic life forms or
      just holes in membranes?
AB  - The large number of ABC transporters in the Arabidopsis genome was made
      responsible for known as well as unexpected aspects in plant development. The
      combination of classical transport experiments with functional genomics
      approaches helped unravel some of these effects. Yet questions concerning the
      importance of this large number of ABC transporters in eukaryotic
      photosynthesizing organisms remain open. Phylogenomic analyses of whole genome
      sequence data reveal comparable sizes and composition between algae and higher
      plants within this protein family. Although this indicates the significance of
      ABC transporters in plants, several other questions remain to be answered.

PMID- 16413547
TI  - LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and
      spindle organization during mitosis.
AB  - LATS2 is a human homolog of Drosophila tumor suppressor lats/warts, and encodes a
      mitotic kinase whose physiological roles remain to be elucidated. We performed
      yeast two-hybrid screening and identified a LIM protein Ajuba, as a binding
      partner of LATS2. LATS2 was localized to the centrosomes throughout the cell
      cycle and was associated with Ajuba during mitosis, contributing to latter's
      mitotic phosphorylation. Depletion of LATS2 or Ajuba impaired centrosomal
      accumulation of gamma-tubulin and spindle formation at the onset of mitosis,
      suggesting that the LATS2-Ajuba complex regulates organization of the spindle
      apparatus through recruitment of gamma-tubulin to the centrosome.

PMID- 16413548
TI  - Does the proteome encode organellar pH?
AB  - Inherent to the proteome itself, may be information that enables proteins to
      buffer pH at a level that promotes their own function within a specialized
      compartment. We observe that the distribution of computed isoelectric points in
      the yeast proteome matches experimentally derived organellar pH estimates across
      distinct subcellular compartments. This raises an interesting evolutionary
      question: did the pI of proteins and the pH of organelles co-evolve to optimize
      function?

PMID- 16413549
TI  - A chloroplastic inner envelope membrane protease is essential for plant
      development.
AB  - Regulated intramembrane proteolysis (RIP) is a fundamental mechanism for
      controlling a wide range of cellular functions. Cleavage of membrane embedded
      proteins results in soluble fragments exerting their function, e.g., as
      transcription factors and thereby regulating gene expression. This process is
      highly conserved throughout all kingdom of life as are the involved proteases.
      RIP has been described in eukaryotes, bacteria and archea though until recently
      not in plant organelles. Here we describe a chloroplastic membrane protease which
      belongs to the conserved S2P family of membrane metallo proteases. We show that
      this protease is localized in the inner envelope membrane and is essential for
      plant development. It could function in a RIP like process regulating the
      concordant action in the plant cytosol, nucleus and plastids.

PMID- 16413550
TI  - Construction of a fully active truncated alternansucrase partially deleted of its
      carboxy-terminal domain.
AB  - Recombinant expression of the large alternansucrase (2057 amino acids) was
      hindered in E. coli due to poor enzyme solubility and protein degradation. The
      effects of deletions of the alternansucrase C-terminal CW-like and APY repeated
      motifs on enzyme solubility and specificity were investigated. A truncated
      variant deleted of the APY repeats but harboring four C-terminal CW-like repeats
      displayed a high specific activity and the same specificity of product synthesis
      as the native enzyme. It is more soluble and suffers less degradation than full
      length alternansucrase. Hence this truncated variant is a promising tool for the
      further structural and kinetic study of this interesting enzyme.

PMID- 16413551
TI  - Things we have learned from tilapia islet xenotransplantation.
AB  - An islet xenotransplantation model has been developed using tilapia (Oreochromis
      niloticus) as the donors. Studies using this model for the treatment of
      experimental type 1 diabetes in mice have produced promising results including
      the maintenance of long-term normoglycemia and mammalian-like glucose tolerance
      profiles in islet graft recipients. Islet encapsulation has also provided a
      promising method for the prevention of graft rejection, and strains of transgenic
      tilapia expressing a [desThrB30] human insulin molecule have been produced. In
      addition to studying islet transplantation for the treatment of type 1 diabetes,
      these studies have also produced insights into piscine glucose homeostasis.
      Studies demonstrating the glucose responsiveness of tilapia islets are described.
      In addition, work performed by our group and by others pertaining to presence and
      nature of piscine glucose transporters is reviewed. Finally, studies addressing
      some of the broader challenges of islet xenotransplantation are discussed with
      particular attention paid to the post-transplantation fate of the various islet
      cell populations and the proteins they produce.

PMID- 16413552
TI  - Pregnancy outcomes of women with eclampsia in Gombe, Nigeria.

PMID- 16413553
TI  - Ethics of justice and ethics of care. Values and attitudes among midwifery
      students on adolescent sexuality and abortion in Vietnam and their implications
      for midwifery education: a survey by questionnaire and interview.
AB  - Adolescent's sexuality and related reproductive health and rights problems are
      sensitive issues in Vietnam. Globalisation has had an impact on the lifestyles of
      young people, and rising numbers of abortion and STI/HIV risks among youth are
      posing major health concerns in the country. These problems need to be addressed.
      Midwives belong to a key category of health personnel in Vietnam, whose task it
      is to promote adolescents' sexual and reproductive health and prevent
      reproductive ill health. It is important to understand future midwives'
      perceptions and attitudes in order to improve their education and training
      programmes. AIM: The aim of this study was to investigate Vietnamese midwifery
      students' values and attitudes towards adolescent sexuality, abortion and
      contraception and their views on professional preparation. METHODS: A
      quantitative survey including 235 midwifery students from four different
      secondary medical colleges in northern Vietnam was carried out in 2003. A
      qualitative study addressing similar questions was performed and 18 midwifery
      students were individually interviewed. FINDINGS: Findings revealed a general
      disapproval of adolescent pre-marital sexual relations and abortion-'an ethics of
      justice'-but also an empathic attitude and willingness to support young women,
      who bear the consequences of unwanted pregnancies and social condemnation-'an
      ethics of care'. Gender-based imbalance in sexual relationships, limited
      knowledge about reproductive health issues among youth, and negative societal
      attitudes were concerns expressed by the students. The students saw their future
      tasks mainly related to childbearing and less to other reproductive health
      issues, such as abortion and prevention of STI/HIV. CONCLUSION: Midwifery
      education in Vietnam should encourage value-reflective thinking around gender
      inequality and ethical dilemmas, in order to prepare midwives to address
      adolescents' reproductive health needs.

PMID- 16413554
TI  - Retention and attrition of certified care assistants in the long-term care
      industry from the Taipei area: an interview survey.
AB  - BACKGROUND/OBJECTIVES: The question, "do certified care assistants (CCAs), after
      finishing their training, devote themselves to the long-term care industry in
      accordance with the original expectations?", is still unknown. Few studies have
      focused on CCAs who have left the long-term care industry. The purposes of this
      study were to identify the employment status of CCAs over the January 2000-July
      2002 time period who had undergone a training program sometime in 1999 and to
      explore the factors affecting whether the CCAs stay or leave the long-term care
      industry in the Taipei area. Understanding retention and attrition of CCAs is
      important for developing the strategies of managing manpower in this industry.
      DESIGN/SETTING/PARTICIPANTS: A descriptive survey design was conducted to
      telephone interview 826 CCAs who had trained during the 1999 certification
      training program in Taipei area. Three hundred and thirteen participants (an
      interview-completed rate of 38%) provided usable data. METHODS: A structured
      interview schedule was developed by authors for interview. Descriptive statistics
      and chi(2) test were adopted to report the subjects' characteristics and factors
      that influenced his/her intention to stay or leave this industry. RESULTS: One
      hundred and sixty-eight respondents (53.7%) had still stayed in this industry,
      while 145 respondents (46.3%) had left already. Major reasons for staying were
      personal interest in caring elderly, good financial benefits from the facility,
      and supportive leadership. In contrast, low wages, heavy workloads, long working
      hours, a high level of stress, and poor financial benefits were factors
      contributing to careers leaving this industry. CONCLUSIONS: Many factors affected
      whether CCAs stayed or left, including personal factors, work-related factors,
      the welfare system, the managerial system, the leadership style and the work
      environment. However, the sequence of these factors and their importance were
      different between two groups. This study has significant implications for
      managing the manpower of the long-term care industry.

PMID- 16413555
TI  - Experiences of recently relocated residents of a long-term care facility in
      Ontario: assessing quality qualitatively.
AB  - BACKGROUND: Canadians overwhelmingly support universal coverage for health
      services and seniors' entitlement to high standards of care in long-term care
      facilities (LTCFs). Government rhetoric reflects these values, but claims of
      fiscal prudence often means translation into policy and improved care is uneven.
      Ontario is moving towards standardized "quality of care" measures, but such
      measures often ignore residents' views and socio-psychological issues. OBJECTIVES
      AND SETTING: Assessment of residents' experiences in a new "state of the art"
      LTCF and their understanding of "quality of care" shortly after relocation from
      two older hospital style facilities. DESIGN AND METHODS: Unobtrusive observations
      of activities of residents and staff in the LTCF by several researchers generated
      an analysis of field notes. In addition, one-on-one, in-depth, semi-structured
      interviews with residents generated qualitative interview data, analyzed
      utilizing a grounded theory approach. PARTICIPANTS: All residents deemed either
      moderately cognitively impaired or not impaired were invited to participate. Of
      these two groups, 18 seniors (five male and 13 female) with a mean age of 84.35yr
      agreed to be interviewed. Participants were all Caucasian and from a wide variety
      of social-economic levels. RESULTS: Two meta-themes "Relationships are the
      foundation of quality care" and "Waiting, activity & grieving loss of personhood"
      best explained residents' experiences of the LTCF. The two meta-themes were inter
      connected and reflected the centrality of socio-psychological "quality of life"
      issues, especially resident-staff relationships as prominent aspects of seniors'
      understanding of quality of care. Improvements in facilities and programs were
      undermined by inattention to staff-patient ratios and continuity in staffing.
      CONCLUSIONS: Seniors said little regarding the fabulous new facility, but
      discussed quality of care as a socio-psychological concept intimately connected
      to staff relations. Government and administrative inattention to issues of
      sufficient funding for staff, relationship needs and continuity of care for
      seniors threatened to undermine residents' experiences of meaning, as well as any
      potential benefits from facilities and program improvements.

PMID- 16413556
TI  - 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil increases plasma
      HDL-cholesterol in fibrate-treated patients.
AB  - The effect of fibrates on high density lipoprotein (HDL)-cholesterol levels is
      suggested to be mediated by its binding to peroxisome proliferator-activated
      receptor-alpha (PPARalpha). Upon ligand binding, PPARalpha heterodimerizes with
      the 9-cis retinoic acid receptor (RXR) and it is this heterodimer which regulates
      gene expression. We assessed the hypothesis that a combined treatment with
      fibrate plus 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil, as
      a source of 9-cis retinoic acid, would improve the drug's effect on HDL
      cholesterol levels. In an open-labeled first trial, 20 fibrate-treated men with
      plasma HDL-cholesterol levels below 40 mg/dl were given Dunaliella capsules,
      providing 60 mg beta-carotene/day, containing all-trans and 9-cis beta-carotene
      (1:1 ratio, w/w). Twenty-two fibrate-treated patients participated in a double
      blind placebo-controlled second trial. Eleven patients were treated with
      Dunaliella capsules, and 11 patients were treated with beta-carotene-deficient
      Dunaliella capsules. Following 6 weeks of the dual treatment plasma HDL
      cholesterol increased by 24.5 and 12.7% in the first and second trials,
      respectively (P=0.002 and 0.012). The dual treatment also increased HDL
      cholesterol levels in human apolipoprotein A-I transgenic mice by 87.5%
      (P=0.021). The results show that a combination treatment of fibrate plus 9-cis
      beta-carotene-rich Dunaliella powder amplifies the effect of the drug on HDL
      cholesterol levels.

PMID- 16413557
TI  - Chromatographic and fluorometric study of interactions between thiophilic and
      hydrophobic ligands and tryptophan peptide homologues.
AB  - The interactions of tryptophan and its peptide homologues with thiophilic ligands
      were studied in terms of their chromatographic retention and steady-state
      fluorescence under various conditions, and compared with non-polar structures
      typically regarded as pure hydrophobic ligands. The experimental results show
      that both non-polar and polar interactions are involved in what has been termed
      "thiophilic adsorption chromatography".

PMID- 16413558
TI  - Determination of folic acid by capillary electrophoresis with chemiluminescence
      detection.
AB  - A rapid and simple method is presented for the determination of folic acid (FA)
      by capillary electrophoresis (CE) with chemiluminescence (CL) detection. This
      method was based on enhance effect of FA on the CL reaction between luminol and
      BrO(-) in alkaline aqueous solution. Optimal separation and determination was
      obtained with an electrophoretic buffer of 35 mM sodium borate (pH 9.4)
      containing 0.8 mM luminol, and an oxidizer solution of 1.6 mM NaBrO in 100 mM
      NaCO(3) buffer solution (pH 12.0). Under the optimal conditions, the
      determination of FA was achieved in less than 20 min, and the detection limit was
      2.0 x 10(-8) M (S/N=3). The relative standard deviations (RSDs) on peak area and
      migration time were in the 1.5 and 1.1%, respectively. The present CE-CL method
      was applied to the determination of FA in commercial pharmaceutical tablets,
      apple juices and human urine.

PMID- 16413559
TI  - Identification of garlic in old gildings by gas chromatography-mass spectrometry.
AB  - The proteinaceous content of garlic (Allium sativum) was characterised according
      to its amino acid composition by using a gas chromatography-mass spectrometry (GC
      MS) analytical procedure. The procedure was tested on fresh and aged garlic
      samples as well as on reference gilding specimens prepared according to old
      recipes. The proteinaceous pattern showed a characteristic distribution of amino
      acids with glutamic acid being the major component. The average amino acidic
      composition was: glutamic acid (Glu; 29%), aspartic acid (Asp; 17%), serine (Ser;
      11%), alanine, glycine, valine, leucine, lysine and phenylalanine (Ala, Gly, Val,
      Leu, Lys and Phe; 5-6%), isoleucine, proline and tyrosine (Ile, Pro and Tyr; 2
      3%), methionine and hydroxyproline (Met and Hyp; 0.5%). In order to distinguish
      this material from animal glue and egg, which are the other proteinaceous media
      commonly used in gilding techniques, a database of amino acid percentages of the
      three proteins was built up and submitted to principal component analysis. Three
      separate clusters were obtained, allowing the protein identification. The
      application of the procedure on several gilding samples from Italian wall and
      easel paintings (13th-17th century) permitted to evidence the use of garlic as a
      gluing agent.

PMID- 16413560
TI  - Determination of 1-nitropyrene metabolites by high-performance liquid
      chromatography with chemiluminescence detection.
AB  - Three metabolites of 1-nitropyrene, i.e., 3-hydoxy-1-nitropyrene (3-OHNP), 6
      hydoxy-1-nitropyrene (6-OHNP) and 8-hydoxy-1-nitropyrene (8-OHNP), were
      sensitively and selectively detected by HPLC with peroxyoxalate chemiluminescence
      (CL) detection. In the system, the three OHNPs were reduced to their
      corresponding amino derivatives through a reduction column packed with Pt/Rh
      coated alumina and then concentrated on a concentrator column. By rotating a
      switching valve, the analytes were eluted into a separator column (ODS),
      separated and then detected by the bis(2,4,6-trichlorphenyl)oxalate-H(2)O(2) CL
      system. The detection limits (signal-to-noise ratio=3) were in the range from
      5fmol (6-OHNP and 8-OHNP) to 12fmol (3-OHNP) per injection. To demonstrate the
      proposed method, it was used to determine three compounds in the incubation
      mixture of 1-nitropyrene and rat S9 mix.

PMID- 16413561
TI  - Monolithic continuous beds as a new generation of stationary phase for
      chromatographic and electro-driven separations.
AB  - Monolithic supports are a new generation of stationary phases which are typically
      prepared using a simple molding process carried out within the confines of the
      capillary. They provide high rates of mass transfer at lower pressure drops,
      enable much faster separations and the nature of the pores allows easy
      permeability for large molecules. This review summarizes the current achievements
      and application of organic polymer-based monolithic columns, silica-based
      monolithic columns and their application in bioaffinity processing, modern
      biotechnology, determination of microorganisms and chiral separations. Special
      attention is paid to microfabricated devices with monolithic supports because
      their fabrication of particles directly in the channel eliminates the need for a
      frit and also creates a unique homogeneity of packing.

PMID- 16413562
TI  - Determination of isoflavones in dietary supplements containing soy, Red Clover
      and kudzu: extraction followed by basic or acid hydrolysis.
AB  - Isoflavones are phytochemicals found in many plants. Because of their structural
      similarity to beta-estradiol, health benefits of isoflavones have been evaluated
      in age-related and hormone-dependent diseases. Dietary supplement preparations
      contain extracts from soy, Red Clover and kudzu. Soy products contain primarily
      genistein, daidzein, and glycitein, while Red Clover products contain primarily
      formononetin and biochanin A. Kudzu extracts contain puerarin and daidzein among
      other components. Previous methods of analysis focused on the determination of
      isoflavones from a single botanical source, while dietary supplements are often a
      blend of extracts from different plants. We developed a method for the analysis
      of isoflavones in dietary supplements regardless of their botanical composition,
      using HPLC-PDA because of its applicability to routine analysis. Isoflavones are
      found as free compounds, glucoside derivatives, 6''-O-malonyl-beta-d-glucoside
      and 6''-O-acetyl-beta-d-glucoside derivatives. In this study, the samples were
      extracted at room temperature with 50:50 (v/v) MeCN/water, and then analyzed
      before and after hydrolyzing the isoflavones by acid or basic digestion. 2'
      Methoxy-flavone and 6-methoxy-flavone were used as internal standards and were
      added together to every sample. Daidzein, glycitein, genistein, puerarin,
      calycosin, pratensein, pseudobaptigenin, formononetin, biochanin A and prunetin
      were among the isoflavones determined.

PMID- 16413563
TI  - Optimising reversed-phase liquid chromatographic separation of an acidic mixture
      on a monolithic stationary phase with the aid of response surface methodology and
      experimental design.
AB  - An optimization strategy for the separation of an acidic mixture by employing a
      monolithic stationary phase is presented, with the aid of experimental design and
      response surface methodology (RSM). An orthogonal array design (OAD) OA(16)
      (2(15)) was used to choose the significant parameters for the optimization. The
      significant factors were optimized by using a central composite design (CCD) and
      the quadratic models between the dependent and the independent parameters were
      built. The mathematical models were tested on a number of simulated data set and
      had a coefficient of R(2) > 0.97 (n = 16). On applying the optimization strategy,
      the factor effects were visualized as three-dimensional (3D) response surfaces
      and contour plots. The optimal condition was achieved in less than 40 min by
      using the monolithic packing with the mobile phase of methanol/20 mM phosphate
      buffer pH 2.7 (25.5/74.5, v/v). The method showed good agreement between the
      experimental data and predictive value throughout the studied parameter space and
      were suitable for optimization studies on the monolithic stationary phase for
      acidic compounds.

PMID- 16413564
TI  - Electric forces induced by a charged colloid particle attached to the water
      nonpolar fluid interface.
AB  - Here, we solve the problem about the electric field of a charged dielectric
      particle, which is adsorbed at the water-nonpolar fluid (oil, air) boundary. The
      solution of this problem is a necessary step for the theoretical prediction of
      the electrodipping force acting on such particle, as well as of the electrostatic
      repulsion and capillary attraction between two adsorbed particles. In accordance
      with the experimental observations, we consider the important case when the
      surface charges are located at the particle-nonpolar fluid boundary. To solve the
      electrostatic problem, the Mehler-Fock integral transform is applied. In the
      special case when the dielectric constants of the particle and the nonpolar fluid
      are equal, the solution is obtained in a closed analytical form. In the general
      case of different dielectric constants, the problem is reduced to the numerical
      solution of an integral equation, which is carried out by iterations. The long
      range asymptotics of the solution indicates that two similar particles repel each
      other as dipoles, whose dipole moments are related to the particle radius,
      contact angle, dielectric constant and surface charge density. The investigated
      short-range asymptotics ensures accurate calculation of the electrodipping force.
      For a fast and convenient application of the obtained results, the derived
      physical dependencies are tabulated as functions of the contact angle and the
      dielectric constants.

PMID- 16413565
TI  - Characterization of micelle formation of dodecyldimethyl-N-2-phenoxyethylammonium
      bromide in aqueous solution.
AB  - Aggregation behavior of dodecyldimethyl-N-2-phenoxyethylammonium bromide commonly
      called domiphen bromide (DB) was studied in aqueous solution. The Krafft
      temperature of the surfactant was measured. The surfactant has been shown to form
      micellar structures in a wide concentration range. The critical micelle
      concentration was determined by surface tension, conductivity, and fluorescence
      methods. The conductivity data were also employed to determine the degree of
      surfactant counterion dissociation. The changes in Gibb's free energy, enthalpy,
      and entropy of the micellization process were determined at different
      temperature. The steady-state fluorescence quenching measurements with pyrene and
      N-phenyl-1-naphthylamine as fluorescence probes were performed to obtain micellar
      aggregation number. The results were compared with those of
      dodecyltrimethylammonium bromide (DTAB) surfactant. The micelle formation is
      energetically more favored in DB compared to that in DTAB. The 1H-NMR spectra
      were used to show that the 2-phenoxyethyl group, which folds back onto the
      micellar surface facilitates aggregate formation in DB.

PMID- 16413566
TI  - A multi-scale assessment of Pb(II) sorption on dolomite.
AB  - Macroscopic sorption studies indicated that Pb sorption capacity was independent
      of pH over the pH range 5-7, while sorption as a function of reaction time up to
      two weeks for systems with no bulk precipitate phases showed continuous Pb uptake
      on dolomite. This could be due to diffusion of Pb into the micropores of dolomite
      as well as an increase in surface sites caused by particle size reduction during
      suspension mixing. Normalized XANES spectra for systems undersaturated with
      respect to Pb carbonate precipitates resembled the spectrum of Pb4(OH)4(4+),
      suggesting that Pb is mainly coordinated to dolomite as an inner-sphere surface
      complex. On the other hand, the XANES spectrum for 10(-3) M Pb at 1 atm CO2(g) in
      a 2 M Mg(NO3)2 background electrolyte solution resembled that of cerussite, while
      a sample at 5 x 10(-4) M Pb in equilibrium with air and 2 M Mg(NO3)2 resembled
      that of hydrocerussite. EXAFS analyses of sorption samples in chloride solutions
      showed that there were only first-shell contributions under 1 atm CO2(g), while
      higher shell contributions from Ca/Mg were seen at 10(-3.42) atm CO2(g). On the
      other hand, EXAFS samples prepared in nitrate solutions showed noticeable
      differences in speciation under different reaction conditions-from outer-sphere
      surface complexes at low Pb concentrations and pH, to inner-sphere surface
      complexes at moderate Pb concentrations and neutral pH, to the formation of Pb
      carbonate precipitates at the highest Pb loadings.

PMID- 16413567
TI  - Modification of a montmorillonite-illite clay using alkaline hydrothermal
      treatment and its application for the removal of aqueous Cs+ ions.
AB  - A montmorillonite-illite clay was modified using alkaline hydrothermal treatment
      (reflux method) and applied to the removal of aqueous Cs+ ions. The alkaline
      solutions were prepared by dissolving NaOH in seawater and in distilled water,
      and the effect of the two alkaline media on the sorption capacities of the
      modified clay was discussed. The modified materials were characterized using XRD,
      SEM/EDS, and FTIR. As a result of the modification, the original mineral was
      partially transformed into a zeolitic material with spherical morphology. The
      results showed that the modification improved the Cs+ uptake capacity of the
      starting clay, with the clay modified in distilled water medium demonstrating
      higher sorption capacity. The sorption data were adequately described using the
      Freundlich and Dubinin-Radushkevich isotherm models.

PMID- 16413568
TI  - Polydispersed O/W emulsions in porous media: segregation at low-tension
      conditions.
AB  - The segregation of polydispersed oil was studied in theoretical models, sand
      packs, and plugs from consolidated cores at low tension and atmospheric
      conditions. The height of the oil belt formed at the top of the porous column and
      its change in time were measured. The analysis of the segregation curves
      indicates the subsequent appearance and rise of three pseudo-phases. The primary
      phase, which contains the dominant fraction of oil in the system, rises with a
      relatively high steady state velocity. Unsteady state and decreasing velocity
      characterize the transitional secondary phase which is a lean emulsion left
      behind. The ternary phase, which follows it with a semi-steady state low
      velocity, is a lean emulsion of the smallest oil blobs present in low
      concentration. The process terminates at the segregation of the mobile oil
      particles in the subsequent phases where a small fraction of the total oil
      content remains in the porous bed, mainly from the last stage of segregation due
      to the entrapment in suitable microstructures. According to the postulated
      mechanism, the decreasing probability of the repeated coalescence in pore bodies
      and dispersion at the connecting pore throats are responsible for the development
      of the mobile phases at the sufficiently low-tension conditions. The structure of
      the pore network, the size-distribution of the oil droplets, the density of their
      population, and the length of paths affect the mechanism, properties, and
      behaviour of the systems.

PMID- 16413569
TI  - Adsorption of novel thermosensitive graft-copolymers: Core-shell particles
      prepared by polyelectrolyte multilayer self-assembly.
AB  - The adsorption properties of thermosensitive graft-copolymers are investigated
      with the aim of developing self-assembled multilayers from these copolymers. The
      copolymers consist of a thermoreversible main chain of poly(N-isopropylacrylamid)
      and a weak polyelectrolyte, poly(2-vinylpyridine), as grafted side chains. Zeta
      potential, single particle light scattering and adsorption isotherms monitor the
      adsorption of the thermoreversible copolymers to precoated colloidal particles.
      The results show a smaller surface coverage for a larger density of grafted
      chains. The surface coverage is discussed in terms of surface charge density in
      the adsorbed monolayer. Taking into account the monolayer adsorption properties,
      conditions are developed for the multilayer formation from these copolymers. A
      low pH provides a sufficient charge density of the grafted chains to achieve a
      surface charge reversal of the colloids upon adsorption. The charge reversal
      after each adsorbed layer is monitored by zeta-potential and the increase of the
      thickness is determined by light scattering. Stable and reproducible multilayers
      are obtained. The results imply that the conformation of the thermosensitive
      component in multilayers depends strongly on the grafting density, where the
      polymer with a higher grafting density adsorbs in a flat conformation while that
      with a lower grafting density adsorbs with more loops.

PMID- 16413570
TI  - Immobilization of liposomes onto quartz crystal microbalance to detect
      interaction between liposomes and proteins.
AB  - To study the interaction between liposomes and proteins, intact liposomes were
      immobilized on a metal planar support by chemical binding and/or bioaffinity
      using a quartz crystal microbalance (QCM). A large decrease in the resonance
      frequency of quartz crystal was observed when the QCM, modified by a self
      assembled monolayer (SAM) of carboxythiol, was added to liposome solutions. The
      stable chemical immobilization of intact liposomes onto SAM was judged according
      to the degree with which adsorbed mass depended on the prepared size of
      liposomes, as well as on the activation time of SAMs when amino-coupling was
      introduced, where the liposome coverage of electrodes was 69+/-8% in optimal
      conditions. When avidin-biotin binding was used on amino-coupling liposome
      layers, liposome immobilization finally reached 168% coverage of the electrode
      surface. Denatured protein was also successfully detected according to the change
      in the frequency of the liposome-immobilized QCM. The adsorbed mass of denatured
      carbonic anhydrase from bovine onto immobilized liposomes showed a characteristic
      peak at a concentration of guanidine hydrochloride that corresponded to a molten
      globule-like state of the protein, although the mass adsorbed onto deactivated
      SAM increased monotonously.

PMID- 16413571
TI  - Detection of anti-brain serum antibodies using a semi-quantitative
      immunohistological method.
AB  - The number of autoimmune disorders that may involve the nervous system is
      increasing. The diagnosis of neurological involvement in the context of systemic
      diseases may be helped by the detection of autoantibodies reacting against neural
      autoantigens. If the autoantigen is not known but the target tissue is suspected,
      immunohistochemistry is one of the main techniques used to certify the presence
      of autoantibodies. Autoreactive antibodies are also present in the healthy
      population but in low quantity compared to patients with such diseases.
      Quantification of such autoantibodies could help to discriminate between disease
      and healthy states. We have developed a densitometric immunohistological method
      for the evaluation of human serum anti-neural reactivity. Using a densitometric
      analysis of rat brain sections incubated with the serum from 107 healthy
      subjects, we have defined the baseline of natural anti-neural autoreactivity, and
      the cut-off for subsequent quantification of anti-neural reactivity in patients
      with neurological involvement in the context of autoimmune diseases, including
      systemic lupus erythematosus, paraneoplastic cerebellar degeneration, and stiff
      person syndrome. The test sensitivity was 81% with a positive predictive value of
      52%, a specificity of 89% with a negative predictive value as high as 97%. In
      conclusion, this standardised semi-quantitative procedure makes
      immunohistochemistry a reliable diagnostic test for autoimmune neuropathologies
      and represents an excellent exclusion test for anti-neural autoimmunity.

PMID- 16413572
TI  - Evidence of oral toxicity of Photorhabdus temperata strain K122 against Prays
      oleae and its improvement by heterologous expression of Bacillus thuringiensis
      cry1Aa and cry1Ia genes.
AB  - Photorhabdus temperata strain K122 exhibited oral toxicity against Prays oleae
      with an LC50 of 58.1 x 10(6) cells ml(-1). Recombinant P. temperata strains
      expressing the cry1Aa and/or cry1Ia genes of Bacillus thuringiensis have been
      constructed. The two cry genes, encoding delta-endotoxins, were placed under the
      control of the lac promoter and IPTG dependent expression in P. temperata was
      demonstrated. The presence of the cry genes in K122 resulted in a clear
      improvement of oral toxicity. This improvement was of 6.2-, 6.6-, and 14.6-fold
      for the strains K122(pBCcry1Aa), K122(pBScry1Ia), and K122(pBCcry1Aa +
      pBScry1Ia), respectively. Furthermore, determination of the Synergistic Factor
      between Cry1Aa and Cry1Ia showed that they act synergistically. This work
      demonstrates that the heterologous expression of B. thuringiensis cry genes in P.
      temperata can be used to improve and broaden its host range for insect control.

PMID- 16413573
TI  - Detection and characterisation of three novel species of reovirus (Reoviridae),
      isolated from geographically separate populations of the winter moth Operophtera
      brumata (Lepidoptera: Geometridae) on Orkney.
AB  - Geographically separate populations of winter moth (Operophtera brumata L.) were
      sampled in heather habitats on the Orkney Isles in order to investigate the
      prevalence of virus pathogens. Reoviruses were isolated in 11 of the 13 winter
      moth populations sampled, with 3 novel species being detected. Two species of
      Cypoviridae (CPV) were isolated, Operophtera brumata CPV18 and O. brumata CPV19,
      with one host population suffering 46% infection prevalence of OpbuCPV19. A third
      virus, O. brumata Reovirus (OpbuRV), was isolated from both winter moth and a
      hymenopteran parasitoid wasp, Phobocampe tempestiva, which is abundant in these
      populations. This was identified as a non-occluded reovirus, which was clearly
      able to infect and persist in both the lepidopteran and the hymenopteran host.
      The genomes of the three viruses were characterised using gel electrophoresis and
      the virus structure was investigated using transmission electron microscopy. The
      relationship of these viruses with a baculovirus that also infects winter moth,
      OpbuNPV, was investigated, as well as the association of OpbuRV with P.
      tempestiva. The detection of such viruses is discussed with reference to studies
      of similar viruses in other lepidopteran and hymenopteran host systems.

PMID- 16413574
TI  - Activation of JNK and xanthine oxidase by TNF-alpha impairs nitric oxide-mediated
      dilation of coronary arterioles.
AB  - Elevated levels of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine,
      are associated with coronary artery disease. However, it is unclear whether
      vasodilator function of coronary resistance arterioles is susceptible to TNF.
      Herein, we examined whether TNF can affect endothelium-dependent nitric oxide
      (NO)-mediated dilation of coronary arterioles to adenosine and whether
      inflammatory signaling pathways such as mitogen-activated protein kinases,
      ceramide sphingolipids, and oxidative stress are involved in the TNF-mediated
      effect. To eliminate confounding influences associated with in vivo preparations,
      coronary arterioles from porcine heart were isolated and pressurized without flow
      for in vitro study. Intraluminal treatment with TNF (1 ng/ml, 90 min)
      significantly attenuated the NO release and vasodilation to adenosine. This
      inhibitory effect was not observed in denuded vessels or in the presence of NO
      synthase inhibitor l-NMMA. Histochemical data showed that superoxide production
      and JNK phosphorylation in arteriolar endothelial cells was enhanced by TNF.
      Administration of superoxide scavenger or inhibitors of ceramide-activated
      protein kinase (dimethylaminopurine), JNK (SP600125 and dicumarol), and xanthine
      oxidase (allopurinol) reduced superoxide production as well as restored NO
      release and vasodilation to adenosine. Conversely, the effects of TNF were
      insensitive to inhibitors of p38 (SB203580), ERK (PD98059), NAD(P)H oxidase
      (apocynin), or mitochondrial respiratory chain (rotenone). These data indicate
      that TNF inhibits endothelium-dependent NO-mediated dilation of coronary
      arterioles by ceramide-induced activation of JNK and subsequent production of
      superoxide via xanthine oxidase. Because myocardial ischemia augments adenosine
      production and elevates TNF level, inhibiting adenosine-stimulated endothelial
      release of NO by TNF could contribute to inadequate regulation of coronary blood
      flow during the development of ischemic heart disease.

PMID- 16413575
TI  - Suppression of dynamic Ca(2+) transient responses to pacing in ventricular
      myocytes from mice with genetic calmodulin kinase II inhibition.
AB  - The multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) is
      important for regulating L-type Ca(2+) current (I(Ca)) and cytoplasmic Ca(2+)
      (Ca(2+)(i)) uptake and release from the sarcoplasmic reticulum (SR), key elements
      of the 'Ca(2+)-induced Ca(2+) release' (CICR) mechanism. However, the effects of
      chronic CaMKII inhibition on Ca(2+)(i) responses during CICR are unknown. We
      hypothesized that chronic CaMKII inhibition significantly affects CICR in
      ventricular myocytes. We studied CICR by simultaneously measuring Ca(2+)(i)
      transients and I(Ca) in voltage-clamped ventricular myocytes isolated from a
      recently developed genetic mouse model of cardiac CaMKII inhibition. These
      measurements were repeated in ventricular myocytes from novel mice with cardiac
      CaMKII inhibition lacking phospholamban (PLN), a known CaMKII substrate and a
      negative regulator of Ca(2+)(i) uptake into the SR Ca(2+) store. CaMKII
      inhibition eliminated a pattern of I(Ca) increases called facilitation and
      significantly reduced beat-to-beat and cell-to-cell variability of peak Ca(2+)(i)
      transients in ventricular myocytes with PLN. PLN ablation eliminated I(Ca)
      facilitation even in the absence of CaMKII inhibition and the effects of CaMKII
      inhibition to reduce SR Ca(2+) content and slow SR Ca(2+) uptake were lost in the
      absence of PLN. PLN ablation significantly reduced I(Ca) beat-to-beat variability
      in cells with CaMKII inhibition. These findings show that chronic CaMKII
      inhibition reduces variability of CICR responses in a manner that is partly
      dependent on the presence of PLN.

PMID- 16413576
TI  - Tyrosine plays a dominant functional role in the paratope of a synthetic antibody
      derived from a four amino acid code.
AB  - The antigen-binding fragment Fab-YADS2 recognizes vascular endothelial growth
      factor (VEGF) and was derived from a library with chemical diversity restricted
      to only four amino acids (Tyr, Ser, Ala and Asp). The structure of the
      Fab:antigen complex revealed that the structural paratope is dominated by Tyr
      side-chains. Isothermal titration calorimetry and cell-based assays show that
      restricted chemical diversity does not limit the affinity or specificity of Fab
      YADS2, which behaves in a manner comparable to natural antibodies. Mutagenesis
      experiments reveal that the functional paratope is dominated by Tyr, which
      represents 11 of the 15 functionally important residues. However, mutagenesis
      experiments also indicate that substitution of any of these tyrosine residues by
      Phe does not significantly affect binding to VEGF. Furthermore, saturation
      mutagenesis shows that replacement of three functionally important tyrosine
      residues by combinations of other hydrophobic residues is not only tolerated, but
      can actually improve affinity. The results support a model for naive antigen
      recognition in which large Tyr side-chains establish binding contacts with
      antigen, and small Ser and Ala side-chains serve as auxiliaries that help to
      position Tyr in favorable binding conformations. While Tyr may not be optimal for
      any particular antigen contact, it is nonetheless capable of mediating favorable
      interactions with a diverse array of surfaces. Furthermore, the side-chain
      hydroxyl group makes Tyr significantly more hydrophilic than Phe and other
      hydrophobic amino acids. Increased hydrophilicity may reduce non-specific binding
      in the unbound state, and this may be critical for a naive repertoire that is
      exposed to a diverse range of potential antigenic surfaces. The results show that
      the chemical nature of Tyr endows the amino acid with a privileged role in
      antigen recognition, and this likely explains the high abundance of Tyr in
      natural antigen-binding sites.

PMID- 16413577
TI  - Characterization of dual substrate binding sites in the homodimeric structure of
      Escherichia coli mRNA interferase MazF.
AB  - MazF and MazE constitute a so-called addiction module that is critical for
      bacterial growth arrest and eventual cell death in response to stress. The MazF
      toxin was recently shown to possess mRNA interferase (MIase) activity, and acts
      as a protein synthesis inhibitor by cleaving cellular mRNA. As a cognate
      regulator, the short-lived antitoxin, MazE, inhibits MazF MIase activity and
      hence maintains the delicate homeostasis between these two components. In the
      present study, we have shown that the MazF homodimer contains two symmetric
      binding sites, each of which is capable of interacting with a MazE C-terminal
      peptide, MazEp(54-77). The slow exchange phenomenon between free and peptide
      bound MazF on the NMR timescale indicates relatively high affinities for MazEp(54
      77) at both sites (Kd,K'd < 10(-7) M). However, the observed sequential binding
      behavior suggests a negative cooperativity between the two sites (Kd < K'd). A 13
      base single-stranded DNA, employed as an uncleavable RNA substrate analog, can
      also bind to both sites on the MazF homodimer with moderate affinity (Kd
      approximately 10(-5) -10(-6) M). Chemical shift perturbation data deduced from
      NMR experiments indicates that the two binding sites for the MazEp peptide
      coincided with those for the single-stranded DNA competitive inhibitor. These
      dual substrate-binding sites are located on the concave interface of the MazF
      homodimer, consisting of a highly basic region underneath the S1-S2 loop and two
      hydrophobic regions containing the H1 helix of one subunit and the S3-S4 loop of
      the opposing subunit. We show that the MazF homodimer is a bidentate
      endoribonuclease equipped with two identical binding sites for mRNA processing
      and that a single MazE molecule occupying one of the binding sites can affect the
      conformation of both sites, hence efficiently hindering the activity of MazF.

PMID- 16413578
TI  - Integrated prediction of the helical membrane protein interactome in yeast.
AB  - At least a quarter of all genes in most genomes contain putative transmembrane
      (TM) helices, and helical membrane protein interactions are a major component of
      the overall cellular interactome. However, current experimental techniques for
      large-scale detection of protein-protein interactions are biased against membrane
      proteins. Here, we define protein-protein interaction broadly as co-complexation,
      and develop a weighted-voting procedure to predict interactions among yeast
      helical membrane proteins by optimally combining evidence based on diverse genome
      wide information such as sequence, function, localization, abundance, regulation,
      and phenotype. We use logistic regression to simultaneously optimize the weights
      of all evidence sources for best discrimination based on a set of known helical
      membrane protein interactions. The resulting integrated classifier not only
      significantly outperforms classifiers based on any single genomic feature, but
      also does better than a benchmark Naive Bayes classifier (using a simplifying
      assumption of conditional independence among features). Finally, we apply the
      optimized classifier genome-wide, and construct a comprehensive map of predicted
      helical membrane protein interactome in yeast. This can serve as a guide for
      prioritizing further experimental validation efforts.

PMID- 16413579
TI  - Recognition of oxidatively modified bases within the biotin-binding site of
      avidin.
AB  - Oxidative damage of DNA results in the formation of many products, including 8
      oxodeoxyguanosine, which has been used as a marker to quantify DNA damage.
      Earlier studies have demonstrated that avidin, a protein prevalent in egg-white
      and which has high affinity for the vitamin biotin, binds to 8-oxodeoxyguanosine
      and related bases. In this study, we have determined crystal structures of avidin
      in complex with 8-oxodeoxyguanosine and 8-oxodeoxyadenosine. In each case, the
      base is observed to bind within the biotin-binding site of avidin. However, the
      mode of association between the bases and the protein varies and, unlike in the
      avidin:biotin complex, complete ordering of the protein in this region does not
      accompany binding. Fluorescence studies indicate that in solution the individual
      bases, and a range of oligonucleotides, bind to avidin with micromolar affinity.
      Only one of the modes of binding observed is consistent with recognition of
      oxidised purines when incorporated within a DNA oligomer, and from this structure
      a model is proposed for the selective binding of avidin to DNA containing
      oxidatively damaged deoxyguanosine. These studies illustrate the molecular basis
      by which avidin might act as a marker of DNA damage, although the low levels of
      binding observed are inconsistent with the recognition of oxidised purines
      forming a major physiological role for avidin.

PMID- 16413580
TI  - Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactions.
AB  - BACKGROUND: alpha-Melanocyte stimulating hormone (alpha-MSH) is an endogenous
      peptide that has remarkable anti-inflammatory and antimicrobial effects. These
      activities have been traced to the C-terminal tripeptide Lys-Pro-Val (KPV). A
      dimer composed of two KPV sequences connected with a Cys-Cys linker, (CKPV)2, is
      currently under clinical investigation for antimicrobial use. The present
      research was designed to evaluate effects of (CKPV)(2) on endotoxin-induced host
      reactions in vitro and in vivo. MATERIALS AND METHODS: Effects of (CKPV)2, KPV,
      and [Nle4-dPhe7]-alpha-MSH (NDP-alpha-MSH) on tumor necrosis factor alpha (TNF
      alpha) production were determined: 1) in human peripheral blood mononuclear cells
      (PBMC) stimulated with lipopolysaccharide (LPS) in vitro, and 2) in rats injected
      with LPS i.v. and sacrificed at 1 h. In additional experiments, dialysis
      peritonitis was induced in rats by adding LPS to dialysis fluid. Net
      ultrafiltrate was calculated and concentrations of nitrite (NO2-) and TNF-alpha
      were measured in blood and peritoneal fluid at 7 h. RESULTS: (CKPV)2 inhibited
      TNF-alpha production by LPS-stimulated human PBMC. This small peptide was as
      effective as NDP-alpha-MSH and more potent than KPV. Similar effectiveness was
      observed in vivo: 1 h after LPS injection, the large increase in circulating TNF
      alpha was markedly reduced by (CKPV)2 treatment. In LPS-induced peritonitis,
      (CKPV)2 restored net ultrafiltrate to control values and significantly inhibited
      concentrations of TNF-alpha and NO2- both in plasma and in dialysate.
      CONCLUSIONS: The remarkable capacity of (CKPV)2 to inhibit endotoxin-induced host
      reactions suggests that it may be useful in treatment of inflammatory disorders.

PMID- 16413581
TI  - Diagnostic and predictive value of CSF d-ROM level in influenza virus-associated
      encephalopathy.
AB  - The aim of this study was to assess the validity of serum and CSF oxidative
      status of patients with IE in their initial stage through the d-ROM (Diacron
      Reactive Oxygen Metabolites, Italy) test, compared to those with other
      neurological diseases. The study was conducted on the following four groups: (1)
      influenza virus-associated encephalopathy (IE, n = 8), including four patients
      showing neurological sequelae or mortal; (2) influenza virus-associated febrile
      seizures (IFS, n = 11); (3) febrile convulsion (FC, n = 10): (4) enterovirus
      associated encephalopathy (EE, n = 4), including one patient with neurological
      sequelae. The CSF d-ROM levels in the IE group were significantly higher than
      those in the IFS and the FC groups but not in the EE group. In addition, general
      laboratory findings such as leukocytes, platelets, C-reactive protein, aspartate
      aminotransferase, creatinine, creatinine kinase and LDH, including interleukin-6
      (IL-6), were analyzed in each group. The CSF d-ROM levels in the IE group were
      significantly higher than those in the IFS and FC groups but not in the EE group.
      As for the serum d-ROM levels and general laboratory findings, with the exception
      of CSF IL-6 levels in IE, no significant differences were detected compared with
      the other groups. In patients with IE, the CSF d-ROM levels could be a valid
      predictive biomarker of the severity, and oxidative stress may be related to the
      pathogenesis of IE.

PMID- 16413582
TI  - Complex I deficiency in Persian multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      characterized by the morphological hallmarks of inflammation, demyelination and
      axonal loss. Until now, little attention has been paid to the contribution of
      mitochondrial respiratory chain enzyme activities to MS. In this study, kinetic
      analysis of mitochondrial respiratory chain complex I enzyme (measured as NADH
      ferricyanide reductase) was performed on intact mitochondria isolated from fresh
      skeletal muscle in MS patients (n = 10) and control subjects (n = 11).
      Mitochondrial DNA common deletion and deletions were also tested in MS patients.
      Our findings showed that complex I activities were significantly reduced (P =
      0.007) in patients compared with control. However, we could not find deletion in
      mtDNA of patients with MS. The presupposition of relationship between MS and
      mitochondrial disorders is due to predominant maternal transmission of MS in
      affected parent-child pairs, pathoaetiological role of respiratory chain
      dysfunction in multisystem disorders and important role of it in
      neurodegenerative disorders, a number of patients such as LHON or other mtDNA
      abnormality with developed neurological symptoms indistinguishable from MS and
      similarity of clinical symptoms in mitochondrial disorders to those of MS. This
      study suggested that a biochemical defect in complex I activity may be involved
      in pathogenesis of MS.

PMID- 16413583
TI  - Regulation of cardiac and renal mineralocorticoid receptor expression by
      captopril following myocardial infarction in rats.
AB  - Myocardial infarction (MI) activates the renin-angiotensin system in the heart
      and increases local production of aldosterone. This hormone may increase reactive
      fibrosis in the myocardium favoring heart failure development. To elucidate the
      potential contribution of aldosterone to cardiac remodeling following MI, we
      evaluated the expression of mineralocorticoid receptors (MCR) in the left
      ventricle (LV) and kidney of rats after MI and captopril treatment. MI was
      induced by ligation of the coronary artery in Wistar rats, which were separated
      into (1) sham-operated group, (2) MI group, (3) MI-captopril treated group (cap,
      50 mg kg(-1) day(-1)). One month later angiotensin converting enzyme (ACE)
      activity was assayed in the plasma, LV and kidney. Cardiac and renal angiotensin
      II (Ang II) levels were determined by ELISA and MCR mRNA expression and protein
      were measured by Taqman RT-PCR and Western blot, respectively. Cardiac MCR mRNA
      and protein levels increased nearly by 80% after MI and Cap treatment normalized
      cardiac MCR protein and mRNA expression. Kidney MCR expression was not affected.
      ACE activity increased 34% in the plasma and 83% in the LV after MI. This
      increase was prevented by Cap. Ang II concentration increased 225% in the LV and
      193% in kidney, which was partially attenuated by Cap. Our data demonstrate
      upregulation of MCR in the heart following MI what may facilitate the effects of
      aldosterone in the ventricular remodeling process. ACE inhibitors may reduce
      reactive fibrosis not only by decreasing Ang II production but also by
      attenuating the aldosterone-signaling pathway by decreasing the expression of MCR
      receptors.

PMID- 16413585
TI  - The muddle of 'Biodiversity'.

PMID- 16413584
TI  - Multiple biological activities of curcumin: a short review.
AB  - Turmeric (Curcuma longa rhizomes), commonly used as a spice is well documented
      for its medicinal properties in Indian and Chinese systems of medicine. It has
      been widely used for the treatment of several diseases. Epidemiological
      observations, though inconclusive, are suggestive that turmeric consumption may
      reduce the risk of some form of cancers and render other protective biological
      effects in humans. These biological effects of turmeric have been attributed to
      its constituent curcumin that has been widely studied for its anti-inflammatory,
      anti-angiogenic, anti-oxidant, wound healing and anti-cancer effects. As a result
      of extensive epidemiological, clinical, and animal studies several molecular
      mechanisms are emerging that elucidate multiple biological effects of curcumin.
      This review summarizes the most interesting in vitro and in vivo studies on the
      biological effects of curcumin.

PMID- 16413586
TI  - Monitoring biological effects of pollution in the Baltic Sea: neglected--but
      still wanted?
AB  - In the Baltic Sea, studies regarding biological effects of contaminants are
      relatively few, partly due to political and economical reasons, specific
      hydrographic characteristics, and a strong eutrophication-targeted research focus
      during the past three decades. The development of a monitoring strategy
      concerning biological effects and its implementation into environmental
      monitoring programmes in the Baltic Sea is lagging behind the progress currently
      taking place in most of western and southern Europe. The pan-European project
      BEEP (Biological Effects of Environmental Pollution on Marine Coastal Ecosystems,
      2001-2004) included the Baltic Sea as one of the target areas for the evaluation
      of a suite of biological effects indicators in European coastal waters. The main
      aims of the BEEP project are described and how the expected outcome for the
      Baltic Sea could provide the needed "baseline" information and expertise for a
      biological effect monitoring and contribute to harmonise environmental monitoring
      programmes within the EU.

PMID- 16413587
TI  - Bystander effects in unicellular organisms.
AB  - Radiation-induced bystander effects have been seen in mammalian cells from
      diverse origins. These effects can be transmitted through the medium to cells not
      present at the time of irradiation. We have developed an assay for detecting
      bystander effects in the unicellular eukaryote, the fission yeast
      Schizosaccharomyces pombe. This assay allows maximal exposure of unirradiated
      cells to cells that have received electron beam irradiation. S. pombe cells were
      irradiated with 16-18 MeV electrons from a pulsed electron LINAC. When survival
      of the irradiated cells decreased to approximately 50%, forward-mutation to 2
      deoxy-d-glucose resistance increased in the unirradiated bystander cells. Further
      increase in dose had no additional effect on this increase. In order to detect
      this response, it was necessary for the irradiated cell/unirradiated cell ratio
      to be high. Other cellular stresses, such as heat treatment, UV irradiation, and
      bleomycin exposure, also caused a detectable response in untreated cells grown
      with the treated cells. We discuss evolutionary implications of these results.

PMID- 16413588
TI  - Characterization of a GDP-D-mannose 3'',5''-epimerase from rice.
AB  - The enzymatic characterization of GDP-d-mannose 3'',5''-epimerase (GME), a key
      enzyme in the biosynthesis of vitamin C in plants is described. The GME gene
      (Genbank Accession No. AB193582) in rice was cloned, and expressed as a fusion
      protein in Escherichia coli. Reaction products from GDP-d-mannose, as produced by
      GME catalysis, were separated by recycling HPLC on an ODS column, and were
      determined to be GDP-l-galactose and GDP-l-gulose, based on their NMR spectra and
      sugar analysis. The reaction catalyzed by GME was inhibited by GDP, and was
      strongly accelerated by NAD(+) in contrast to the case of GME from Arabidopsis
      thaliana. This difference in the effect of NAD(+) on GME activity can be
      attributed to the NAD binding domain which is conserved in the rice gene, but not
      in the Arabidopsis thaliana gene. The apparent K(m) and k(cat) were determined to
      be 1.20x10(-5)M and 0.127s(-1), respectively, in the presence of 20microM NAD(+).
      The fractions of GDP-d-mannose, GDP-l-galactose and GDP-l-gulose, at equilibrium,
      were approximately 0.75, 0.20 and 0.05, respectively.

PMID- 16413589
TI  - Simulation of long-haul flights in humans: prolonged mild hypoxia does not alter
      the circadian time structure of plasma testosterone and gonadotrophins.
AB  - Mild hypobaric hypoxia caused by pressurisation may contribute to alter
      rhythmicity after long-haul flights, independently of the number of time zones
      crossed. In this controlled crossover study, we assessed the effects of two
      levels of hypoxia, equivalent to 8000 ft and 12,000 ft above sea level, on the
      rhythm of plasma concentrations of three hormones: testosterone, LH, and FSH. A
      hypoxia-induced decrease in LH and FSH has often been reported during
      mountaineering while testosterone is considered a marker of fatigue. Sixteen
      healthy male volunteers, aged 23-39 years, spent 8 h in a hypobaric chamber
      (08:00-16:30), simulating conditions at 8000 ft. This was followed by an
      additional 8 h four weeks later, simulating conditions at 12,000 ft. Plasma
      hormones were assayed every 2 h over two 24-h cycles (control and hypoxic
      exposure cycles). We found no significant effects of hypoxia on the circadian
      profile of the gonadal axis hormones and, therefore, conclude that these hormones
      do not serve as valuable markers of post-flight alterations of the circadian
      system in human.

PMID- 16413591
TI  - Sodium arsenite impairs insulin secretion and transcription in pancreatic beta
      cells.
AB  - Human studies have shown that chronic inorganic arsenic (iAs) exposure is
      associated with a high prevalence and incidence of type 2 diabetes. However, the
      mechanism(s) underlying this effect are not well understood, and practically,
      there is no information available on the effects of arsenic on pancreatic beta
      cells functions. Thus, since insulin secreted by the pancreas plays a crucial
      role in maintaining glucose homeostasis, our aim was to determine if sodium
      arsenite impairs insulin secretion and mRNA expression in single adult rat
      pancreatic beta-cells. Cells were treated with 0.5, 1, 2, 5 and 10 microM sodium
      arsenite and incubated for 72 and 144 h. The highest dose tested (10 microM)
      decreased beta-cell viability, by 33% and 83%, respectively. Insulin secretion
      and mRNA expression were evaluated in the presence of 1 and 5 microM sodium
      arsenite. Basal insulin secretion, in 5.6 mM glucose, was not significantly
      affected by 1 or 5 microM treatment for 72 h, but basal secretion was reduced
      when cells were exposed to 5 microM sodium arsenite for 144 h. On the other hand,
      insulin secretion in response to 15.6 mM glucose decreased with sodium arsenite
      in a dose-dependent manner in such a way that cells were no longer able to
      distinguish between different glucose concentrations. We also showed a
      significant decrease in insulin mRNA expression of cells exposed to 5 microM
      sodium arsenite during 72 h. Our data suggest that arsenic may contribute to the
      development of diabetes mellitus by impairing pancreatic beta-cell functions,
      particularly insulin synthesis and secretion.

PMID- 16413592
TI  - Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent
      vaccine administered to children in a day care setting.
AB  - The genetic and phenotypic stability of viruses isolated from young children
      following intranasal administration of the trivalent live-attenuated influenza
      virus vaccine (LAIV, marketed in the United States as FluMist) was evaluated by
      determination of genomic sequence and assessment of the cold-adapted (ca),
      temperature-sensitive (ts) and attenuated (att) phenotypes. The complete genomic
      sequence was determined for 56 independent isolates obtained from children
      following vaccination (21 type A/H1N1, 12 A/H3N2, 1 A/H3N1 and 22 type B
      viruses), 20% of which had no nucleotide misincorporations compared with
      administered vaccine. The remaining isolates had from one to seven changes per
      genome. None of the observed misincorporations resulted in predicted amino acid
      codon substitutions at sites previously shown to contribute to the ca, ts or att
      phenotypes, and all vaccine-derived isolates retained ca and ts phenotypes
      consistent with the observation that none of the vaccine recipients displayed
      distinctive symptoms. The results indicate that LAIV strains undergo very limited
      genetic change following replication in vaccine recipients and that those changes
      did not affect vaccine attenuation.

PMID- 16413594
TI  - A finite-element analysis model of orbital biomechanics.
AB  - To reach a better understanding of the suspension of the eye in the orbit, an
      orbital mechanics model based upon finite-element analysis (FEA) has been
      developed. The FEA model developed contains few prior assumptions or constraints
      (e.g., the position of the eye in the orbit), allowing modeling of complex three
      dimensional tissue interactions; unlike most current models of eye motility.
      Active eye movements and forced ductions were simulated and showed that the
      supporting action of the orbital fat plays an important role in the suspension of
      the eye in the orbit and in stabilization of rectus muscle paths.

PMID- 16413593
TI  - Three-dimensional structure and stoichiometry of Helmintosporium victoriae190S
      totivirus.
AB  - Most double-stranded RNA viruses have a characteristic capsid consisting of 60
      asymmetric coat protein dimers in a so-called T = 2 organization, a feature
      probably related to their unique life cycle. These capsids organize the
      replicative complex(es) that is actively involved in genome transcription and
      replication. Available structural data indicate that their RNA-dependent RNA
      polymerase (RDRP) is packaged as an integral capsid component, either as a
      replicative complex at the pentameric vertex (as in reovirus capsids) or as a
      fusion protein with the coat protein (as in some totivirus). In contrast with
      members of the family Reoviridae, there are two well-established capsid
      arrangements for dsRNA fungal viruses, exemplified by the totiviruses L-A and UmV
      and the chrysovirus PcV. Whereas L-A and UmV have a canonical T = 2 capsid, the
      PcV capsid is based on a T = 1 lattice composed of 60 capsid proteins. We used
      cryo-electron microscopy combined with three-dimensional reconstruction
      techniques and hydrodynamic analysis to determine the structure at 13.8 A
      resolution of Helminthosporium victoriae 190S virus (Hv190SV), a totivirus
      isolated from a filamentous fungus. The Hv190SV capsid has a smooth surface and
      is based on a T = 2 lattice with 60 equivalent dimers. Unlike the RDRP of some
      other totiviruses, which are expressed as a capsid protein-RDRP fusion protein,
      the Hv190SV RDRP is incorporated into the capsid as a separate, nonfused protein,
      free or non-covalently associated to the capsid interior.

PMID- 16413595
TI  - Application of a constructed wetland for industrial wastewater treatment: a pilot
      scale study.
AB  - The main objective of this study was to examine the efficacy and capacity of
      using constructed wetlands on industrial pollutant removal. Four parallel pilot
      scale modified free water surface (FWS) constructed wetland systems [dimension
      for each system: 4-m (L)x1-m (W)x1-m (D)] were installed inside an industrial
      park for conducting the proposed treatability study. The averaged influent
      contains approximately 170 mg l(-1) chemical oxygen demand (COD), 80 mg l(-1)
      biochemical oxygen demand (BOD), 90 mg l(-1) suspend solid (SS), and 32 mg l(-1)
      NH(3)-N. In the plant-selection study, four different wetland plant species
      including floating plants [Pistia stratiotes L. (P. stratiotes) and Ipomoea
      aquatica (I. aquatica)] and emergent plants [Phragmites communis L. (P. communis)
      and Typha orientalis Presl. (T. orientalis)] were evaluated. Results show that
      only the emergent plant (P. communis) could survive and reproduce with a
      continuous feed of 0.4m(3)d(-1) of the raw wastewater. Thus, P. communis was used
      in the subsequent treatment study. Two different control parameters including
      hydraulic retention time (HRT) (3, 5, and 7d) and media [vesicles ceramic
      bioballs and small gravels, 1cm in diameter] were examined in the treatment
      study. Results indicate that the system with a 5-d HRT (feed rate of 0.4m(3)d(
      1)) and vesicles ceramic bioballs as the media had the acceptable and optimal
      pollutant removal efficiency. If operated under conditions of the above
      parameters, the pilot-plant wetland system can achieve removal of 61% COD, 89%
      BOD, 81% SS, 35% TP, and 56% NH(3)-N. The treated wastewater meets the current
      industrial wastewater discharge standards in Taiwan.

PMID- 16413596
TI  - Metric variation and sexual dimorphism in the dentition of Ouranopithecus
      macedoniensis.
AB  - The fossil sample attributed to the late Miocene hominoid taxon Ouranopithecus
      macedoniensis is characterized by a high degree of dental metric variation. As a
      result, some researchers support a multiple-species taxonomy for this sample.
      Other researchers do not think that the sample variation is too great to be
      accommodated within one species. This study examines variation and sexual
      dimorphism in mandibular canine and postcanine dental metrics of an
      Ouranopithecus sample. Bootstrapping (resampling with replacement) of extant
      hominoid dental metric data is performed to test the hypothesis that the
      coefficients of variation (CV) and the indices of sexual dimorphism (ISD) of the
      fossil sample are not significantly different from those of modern great apes.
      Variation and sexual dimorphism in Ouranopithecus M(1) dimensions were
      statistically different from those of all extant ape samples; however, most of
      the dental metrics of Ouranopithecus were neither more variable nor more sexually
      dimorphic than those of Gorilla and Pongo. Similarly high levels of mandibular
      molar variation are known to characterize other fossil hominoid species. The
      Ouranopithecus specimens are morphologically homogeneous and it is probable that
      all but one specimen included in this study are from a single population. It is
      unlikely that the sample includes specimens of two sympatric large-bodied
      hominoid species. For these reasons, a single-species hypothesis is not rejected
      for the Ouranopithecus macedoniensis material. Correlations between mandibular
      first molar tooth size dimorphism and body size dimorphism indicate that O.
      macedoniensis and other extinct hominoids were more sexually size dimorphic than
      any living great apes, which suggests that social behaviors and life history
      profiles of these species may have been different from those of living species.

PMID- 16413597
TI  - The influence of living habits and family relationships on element concentrations
      in human hair.
AB  - The paper discusses the content of elements in hair of subjects studied over
      several years. The study was performed on 5 subjects (N=28) that lived together
      or were family related. The elemental composition of hair of the studied subjects
      was compared with the average content of the population living in the same urban
      area (Wroclaw city, south-west Poland), with the population of a non
      industrialized area in Poland (Silesian Beskid), as well as with the population
      of north-east Sweden and Rio de Janeiro. When comparing the composition of hair
      from the studied subjects with the people living in the same city, it was found
      that the differences resulted mainly from different living habits (Na, Si, Co,
      Fe, Mn, Zn) and local exposure (Pb, Cd, Al). When comparing with the reference
      material for unexposed population, it was found that the studied subjects were
      exposed to Al. Time profile of element contents in hair of a given person showed
      that the level changed significantly (even several fold) with changes of living
      habits or environmental exposure. Also, it was found that there were similar
      tendencies in the accumulation of the majority of elements by people that lived
      together. The effect of living habits on the level of a given element was found
      to be stronger than the influence of either sex or family relationship. The paper
      also discusses inter-element interactions within the studied group. Statistically
      significant (p<0.05) correlations were found between elements that occur
      together: Ca-Mg, Fe-Mn, Na-K, Co-K, Au-Pt, Cd-Pb. In order to determine the
      influence of various elements on the content of another element, linear multiple
      regression was performed that revealed the following relationships: Ca=f(Mn, Sr),
      Na=f(K, Mn), K=f(V, Ti).

PMID- 16413598
TI  - Radionuclides in fruit systems: model prediction-experimental data
      intercomparison study.
AB  - This paper presents results from an international exercise undertaken to test
      model predictions against an independent data set for the transfer of
      radioactivity to fruit. Six models with various structures and complexity
      participated in this exercise. Predictions from these models were compared
      against independent experimental measurements on the transfer of 134Cs and 85Sr
      via leaf-to-fruit and soil-to-fruit in strawberry plants after an acute release.
      Foliar contamination was carried out through wet deposition on the plant at two
      different growing stages, anthesis and ripening, while soil contamination was
      effected at anthesis only. In the case of foliar contamination, predicted values
      are within the same order of magnitude as the measured values for both
      radionuclides, while in the case of soil contamination models tend to under
      predict by up to three orders of magnitude for 134Cs, while differences for 85Sr
      are lower. Performance of models against experimental data is discussed together
      with the lessons learned from this exercise.

PMID- 16413599
TI  - Evaluation of blood collection tubes.

PMID- 16413600
TI  - Not qualified--a patient's perspective.

PMID- 16413601
TI  - Remission of a negative Her2/Neu overexpressive metastatic ovarian cancer patient
      by the single agent of trastuzumab as salvage therapy.

PMID- 16413602
TI  - Evidence for an involvement of peripheral serotonin in p-chloroamphetamine
      induced ejaculation of rats.
AB  - The purpose of the present study was to determine the mechanism of the
      ejaculatory response induced by the 5-HT-releasing compound p-chloroamphetamine
      (PCA) in rats. The ejaculatory response was assessed by weighing the coagulated
      seminal materials accumulated over 1 h. Intraperitoneal injection of PCA (0.5-5.0
      mg/kg) produced a dose-related increase in both the incidence of ejaculation and
      the weight of the accumulated seminal materials. The ejaculatory response induced
      by PCA (5.0 mg/kg) was abolished by pretreatment with the 5-HT synthesis
      inhibitor p-chlorophenylalanine, the 5-HT receptor antagonists methysergide and
      MDL72222, or by the selective 5-HT reuptake inhibitor citalopram, suggesting that
      the 5-HT-releasing property of PCA mainly involved the expression of ejaculation.
      Neither the section of the spinal cord at thoracic (T8-9) level nor the
      lumbosacral spinal 5-HT denervation by intrathecal (i.t.) injection of 5,7
      dihydroxytryptamine affected the ejaculatory response induced by PCA. The i.t.
      injection of PCA (20-160 microg/rat) at lumbosacral spinal level did not exert
      the systemic PCA-like prominent effect on ejaculation, whereas i.t. injection of
      lidocain at the same site completely abolished the response to systemic PCA.
      Additionally, the peripherally administered 5-HT (0.1 and 0.25 mg/kg, i.p.)
      enhanced the proejaculatory effect at a threshold dose (1.0 mg/kg, i.p.) of PCA.
      From these observations, it is concluded that the ejaculatory response induced by
      PCA is mainly a spinally mediated reflex response that is triggered by the
      release of 5-HT in the peripheral sites.

PMID- 16413603
TI  - Effects of nicotine and epibatidine on locomotor activity and conditioned place
      preference in rats.
AB  - We studied the effects of nicotine and epibatidine given s.c. acutely and
      repeatedly, on locomotor activity and conditioned place preference (CPP) in rats.
      Nicotine at 0.5 mg/kg immediately and at 0.8 mg/kg after a delay increased the
      locomotor activity and its locomotor stimulant effects were greatly sensitized
      (about fourfold) when it was given repeatedly. Acute epibatidine at 0.6 and 3.0
      microg/kg increased the activity modestly after a delay. When given repeatedly
      epibatidine's stimulant effects, mainly those at 3.0 microg/kg, were somewhat
      sensitized (less than twofold). Nicotine at 0.5 and 0.8 mg/kg produced CPP in
      rats in a biased paradigm. Epibatidine elicited CPP at very low dose (0.1
      microg/kg), but at 0.3 or 0.6 microg/kg it induced neither preference nor
      aversion and at the 3.0 microg/kg dose it was aversive. Both acutely and after
      the repeated administration, epibatidine enhanced the locomotor activity of rats
      clearly less than nicotine agreeing with its previously reported lesser effects
      on accumbal dopamine output. Thus, while nicotine elicits CPP at doses (0.5 and
      0.8 mg/kg) equal to those that increase accumbal dopamine output and locomotor
      activity, epibatidine seems to be aversive at the dose (3.0 microg/kg) that
      enhances accumbal dopamine output and increases locomotor activity.

PMID- 16413604
TI  - A comprehensive assessment of the safety of intravenous methamphetamine
      administration during treatment with selegiline.
AB  - Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor
      shown to be effective in the treatment of Parkinson's and Alzheimer's diseases.
      Recent evidence suggests that selegiline may also be useful in treating specific
      aspects of cocaine and nicotine dependence, generating interest in this compound
      for the treatment of methamphetamine addiction. To investigate this, we performed
      a randomized, single-blind, placebo-controlled study to evaluate the safety of
      selegiline treatment (as compared to placebo), concurrent with intravenous
      methamphetamine (15 or 30 mg). Secondary study objectives included determinations
      of plasma levels of selegiline and its metabolites, evaluating whether selegiline
      administration altered the pharmacokinetics of methamphetamine or its
      metabolites, and evaluating whether selegiline treatment alters the subjective
      responses to methamphetamine. Twenty-four methamphetamine-dependent participants
      were randomized to treatment, and 9 of these (N = 5 selegiline, N = 4 placebo)
      completed the entire protocol. The principal finding from this study was that
      intravenous administration of moderate doses of methamphetamine was safely
      tolerated during treatment with selegiline. No participants had electrocardiogram
      changes, and there were no meaningful differences in any laboratory values either
      between groups at screening or as a result of the study procedures. In general,
      adverse events were mild or moderate, and no subjects were discontinued due to
      adverse events or serious adverse events. Selegiline treatment did not enhance
      any of the cardiovascular changes (heart rate, blood pressure) produced by
      methamphetamine administration. Selegiline treatment slightly increased
      methamphetamine associated "bad effects" but did not alter any other subjective
      effects. The elimination half-life of methamphetamine was approximately 12 h, and
      selegiline did not alter clearance of methamphetamine. The available data suggest
      that selegiline is likely to be safe if used as a pharmacotherapy for
      methamphetamine dependence.

PMID- 16413605
TI  - Project Towards No Drug Abuse: long-term substance use outcomes evaluation.
AB  - OBJECTIVES: This paper presents up to 5 years post-program outcomes of Project
      Towards No Drug Abuse (Project TND), a drug abuse prevention program conducted in
      South California alternative high school system during years 1994-1999. METHODS:
      The effects of a 9-session health motivation--social skills--decision-making
      curriculum were evaluated. Twenty-one schools recruited were randomly assigned to
      standard care (control), classroom only, or a classroom plus semester-long school
      as-community component. Last 30-day use of cigarettes, alcohol, marijuana, and
      hard drugs were assessed at three time intervals: short-term (year 1), middle
      term (years 2 or 3), and long-term (years 4 or 5). Multilevel random coefficients
      modeling were employed to estimate the adjusted levels of substance use. RESULTS:
      Among 1578 baseline subjects, follow-up data were available for 68% (year 1), 66%
      (years 2 or 3), and 46% (years 4 or 5) of subjects, respectively. Results
      revealed significant positive long-term program effects for hard drug use at year
      4 or 5 for the two program interventions (P = 0.02). CONCLUSIONS: Project TND
      reduced hard drug use in the 46% who were successfully followed. It is the first
      program to demonstrate long-term self-reported behavioral effects on hard drug
      use among high-risk youth by using a school-based, limited-session model.

PMID- 16413606
TI  - Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2
      transcription.
AB  - Methylglyoxal is a highly reactive dicarbonyl degradation product formed from
      triose phosphates during glycolysis. Methylglyoxal forms stable adducts primarily
      with arginine residues of intracellular proteins. The biologic role of this
      covalent modification in regulating cell function is not known. Here, we report
      that in retinal Muller cells, increased glycolytic flux causes increased
      methylglyoxal modification of the corepressor mSin3A. Methylglyoxal modification
      of mSin3A results in increased recruitment of O-GlcNAc transferase to an mSin3A
      Sp3 complex, with consequent increased modification of Sp3 by O-linked N
      acetylglucosamine. This modification of Sp3 causes decreased binding of the
      repressor complex to a glucose-responsive GC box in the angiopoietin-2 promoter,
      resulting in increased Ang-2 expression. A similar mechanism involving
      methylglyoxal-modification of other coregulator proteins may play a role in the
      pathobiology of a variety of conditions associated with changes in methylglyoxal
      concentration, including cancer and diabetic vascular disease.

PMID- 16413607
TI  - Antifungal efficacy of chitosan and its thiourea derivatives upon the growth of
      some sugar-beet pathogens.
AB  - Chitosan (CS) was modified by reaction with benzoyl thiocyanate to give a
      thiourea derivative (TUCS). The antifungal behavior of chitosan and its thiourea
      derivative was investigated in vitro on the mycelial growth, sporulation and
      germination of conidia or sclerotia of the following sugar-beet: Beta vulgaris
      pathogens isolated in Egypt, Rhizoctonia solani Kuhn (AG(2-2)) Sclerotium rolfsii
      Sacc. and Fusarium solani (Mart.) Sacc. All the prepared thiourea derivatives had
      a significant inhibiting effect on the different stages of development on the
      germination of conidia or sclerotia of all the investigated fungi in the polymer
      concentration range of 5-1000 microg ml(-1). In the absence of chitosan and its
      derivative, R. solani exhibited the fastest growth of the fungi studied. However,
      growth tolerance of the modified chitosan was highest for F. solani and lowest
      for R. solani. The most sensitive to the modified chitosan stress with regard to
      their germination and number produced were the sclerotia of S. rolfsii. It has
      been found that the TUCS is a much better fungicidal agent (about 60 times more)
      than the pure CS against most of the fungal strains tested. The molecular weight
      and the degree of deacetylation were found to have an important effect on the
      growth activities of the pathogens.

PMID- 16413608
TI  - Granzyme-like sequences in bony fish shed light on the emergence of hematopoietic
      serine proteases during vertebrate evolution.
AB  - Hematopoietic serine proteases (SPs) are stored in the granules of different
      leukocytes and these enzymes are important effector molecules in the immune
      system of mammals. However, very little is known about the presence of these
      proteins in lower vertebrates. Herein, the primary structures of five novel fish
      SPs, from the Atlantic cod (Gadus morhua) and the channel catfish (Ictalurus
      punctatus), are presented. One of the cod SPs is a homologue to human GzmA and K.
      The other fish SPs identified are termed 'Gzm-like' and are distantly related to
      a large heterogeneous group of hematopoietic SPs, including most of the T-cell
      Gzms (B-H), the mast cell chymases, the mast cell/basophil proteases of the mouse
      mast cell protease-8 subfamily (M8-family) and the neutrophil cathepsin G.
      Extensive BLAST-searches in genome and expressed sequence tag (EST) databases
      identified 40 additional teleost SPs related to the mammalian hematopoietic SP
      family. Subsequent phylogenetical analyses clearly demonstrate that the
      diversification into different subgroups within the GzmB/chymase/cathepsin G
      related family has occurred independently in bony fishes and in mammals. In
      contrast, our findings suggest that the three subgroups, including (1) GzmK and
      the potent apoptosis-inducing GzmA, (2) the neutrophil proteases (proteinase 3, N
      elastase and azurocidin), and (3) adipsin, have all evolved as distinct groups
      before the separation of tetrapods from the ray-finned fish approximately 420
      million years ago.

PMID- 16413609
TI  - Rapid actions of aldosterone in vascular health and disease--friend or foe?
AB  - The mineralocorticoid receptor (MR) and the enzyme 11betahydroxysteroid
      dehydrogenase type 2, which confers aldosterone specificity to the MR, are
      present in endothelium and vascular smooth muscle. In several pathological
      conditions aldosterone promotes vascular damage by formation of reactive oxygen
      species. The effect of aldosterone on vascular function, however, is far from
      clear. By rapid non-genomic mechanisms aldosterone may cause calcium mobilization
      and vasoconstriction, or may stimulate nitric oxide formation through the PI-3
      kinase/Akt pathway and thereby counteract vasoconstriction. Vasoconstrictor,
      vasodilator or no effects of aldosterone have been reported from studies on human
      forearm blood flow. Inhibition of MR with spironolactone improves endothelial
      function in patients with heart failure but worsens endothelial function in type
      2 diabetic patients. The aim of the present review is to reconcile some of the
      apparently conflicting data. A key observation is that reactive oxygen and
      nitrogen species serve as physiological signaling molecules at low
      concentrations, while they initiate pathological processes at higher
      concentrations. The net effect of aldosterone, which stimulates ROS production,
      therefore depends on the ambient level of oxidative stress. Thus, in situations
      with low levels of oxidative stress aldosterone may promote vasodilatation, while
      at higher oxidative stress (high NaCl intake, pre-existing vascular pathological
      conditions, high oxygen tension in vitro) aldosterone is likely to be associated
      with vasoconstriction and oxidative damage, and in this setting inhibition of the
      MR is likely to be beneficial.

PMID- 16413611
TI  - Impaired emotion processing in remitted patients with bipolar disorder.
AB  - In the present study, we examined whether there is an impairment in affect
      matching abilities in remitted patients with bipolar disorder and if this could
      be attributed to problems with facial perception per se and/or the ability to
      perceive the relative valence of facial expressions indicating emotions. We
      examined 19 patients with bipolar disorder I, currently remitted, and 30 healthy
      controls (15 men), matched on age, education, and gender, using two computerized
      tests: matching facial identity [Kinney's Identity Matching Test (KIMT)] and
      matching facial emotional expressions [Kinney's Affect Matching Test (KAMT)].
      Patients with bipolar disorder performed significantly worse than the healthy
      group on the KAMT, but not on the KIMT. Performance on the KAMT and KIMT did not
      correlate with age of onset and duration of illness, or with manic or depressive
      residual symptoms. The present findings support the differential deficit
      hypothesis regarding impaired affect perception in bipolar disorder during
      remission. Patients' deficits were restricted to the matching of facial emotional
      expressions despite their intact perception of facial identity.

PMID- 16413610
TI  - Neural substrates of cognitive and behavioral deficits in atypical Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a
      progressive cognitive decline that typically affects first memory and later
      executive functions, language, and visuospatial skills. This sequence of
      cognitive deterioration is thought to reflect the progressive invasion of the
      cerebral cortex by the two major pathological hallmarks of AD, neurofibrillary
      tangles (NFT) and senile plaques (SP), as well as degree of neuronal and synaptic
      loss. In atypical AD, prominent and early deficits are found in language, motor
      abilities, frontal and executive capacities, or visuospatial skills. These
      atypical clinical features are associated with an unusual pattern of NFT or SP
      formation that predominantly involves cortical areas usually spared in the course
      of the degenerative process. In an attempt to classify this highly heterogeneous
      subgroup, the present article provides an overview of clinicopathological
      analyses in patients with atypical progression of AD symptomatology with special
      reference to the relationship between specific cognitive and behavioral deficits
      and hierarchical patterns of AD lesion distribution within the cerebral cortex.
      On the basis of these representative examples of a cortical circuit-based
      approach to explore the mechanisms giving rise to AD neuropsychological
      expression, we also critically discuss the possibility to develop a matrix
      linking clinical presentations to degeneration of forward and backward long
      corticocortical pathways in this disorder.

PMID- 16413612
TI  - Genetic association analysis of the glutathione peroxidase (GPX1) gene
      polymorphism (Pro197Leu) with tardive dyskinesia.
AB  - A possible involvement of oxidative stress in the pathophysiology of tardive
      dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A.,
      Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral
      dyskinesias in rats. Implications for tardive dyskinesia? Progress in
      Neurobiology 61, 525-541.]). Long-term administration of neuroleptics alters
      dopaminergic turnover, which results in increased formation of reactive oxygen
      species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a
      consequence of oxidative stress. In the present study, the relationship between
      TD and a possible functional polymorphism of the human glutathione peroxidase
      (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment
      refractory patients with schizophrenia. A proline (Pro) to leucine (Leu)
      substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No
      significant difference in total Abnormal Involuntary Movements Scale (AIMS)
      scores was observed among patients in the three genotype groups. Moreover, no
      significant differences in genotype or allele frequencies were observed between
      subjects with and without TD. Our results suggest that the GPX1 gene polymorphism
      does not confer increased susceptibility to TD, although further studies are
      warranted before a conclusion can be drawn.

PMID- 16413613
TI  - Anti-erythrocyte natural antibody activity in the unconventional 'heavy chain'
      immunoglobulins of Indian desert camel (Camelus dromedarius).
AB  - Members of the family Camelidae contain unconventional 'heavy chain' antibodies
      (HCAbs) that are devoid of light chains (LCs) in their structure and occur under
      physiological conditions. The spectrum of antigenic specificities in HCAbs and
      hence their biological significance is not known at present. Recent studies have
      however indicated that they contribute significantly towards the immunoglobulin
      (Ig) receptor diversity. The present study was planned to investigate the natural
      antibody (NAb) activity in camel HCAbs as further indication of the wide spectrum
      of their antigenic specificities. Detection of NAbs in the sera and isolated
      HCAbs of Indian Thar desert camels was undertaken against erythrocyte antigens (E
      Ags) from eleven animal species including nine mammals, chicken and frog by using
      direct haemagglutination (HA) and indirect Coombs' test. HCAbs were found to
      behave as 'incomplete antibodies' and agglutinated erythrocytes of different
      animal species in indirect Coombs' test using rabbit anti-camel IgG3 (HCAbs)
      antiserum. Variations were noticed in the Coombs' titres against erythrocytes
      from different species. HCAbs also reacted against E-Ags in immunoblots. These
      findings provide further evidence that camelid HCAbs are produced against diverse
      antigens (Ags) under natural conditions, thereby contributing to camelid Ig
      receptor diversity.

PMID- 16413614
TI  - Dissection of the genetic complexity of arthritis using animal models.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease directed towards
      peripheral joints. As all common diseases it is associated with several genes and
      a multitude of environmental factors. In addition, in similarity with most other
      complex diseases, it is defined only on the basis of clinical signs and symptoms,
      it is therefore more properly classified as a syndrome rather than a distinct
      disease entity. This complexity of RA has led to difficulties in finding the
      underlying genes. In spite of large efforts it is still only the MHC class II
      region that reaches genome wide significance in confirmed studies. However, this
      has been known for decades and we are still unable to conclusively identify the
      underlying gene/s. We hypothesize that an MHC class II gene is involved and
      although we have detailed knowledge on both structure and function we do not know
      its possible pathogenic role in RA. In this review I will argue for the
      usefulness of animal models as a tool to identify genes and pathways associated
      with disease. The examples to be discussed are genes controlling the oxidative
      burst pathways and MHC class II genes.

PMID- 16413615
TI  - Comparison of different brands of IVIg in an in vitro model of immune neuropathy.
AB  - Intravenous immunoglobulin (IVIg) is used for the treatment of a number of
      autoimmune neurological disorders. Whether different brands of IVIg or different
      lots of the same brand are comparably efficacious for the treatment of
      neurological disorders is not clear. To examine this issue we compared the
      efficacy of different brands and/or lots of IVIg in a cell culture model of
      immune neuropathy. We report that products examined were equally effective and
      there was no lot-to-lot variability in our experimental model. These findings
      support the notion that efficacy of different IVIg products is comparable in a
      standardized model.

PMID- 16413616
TI  - Expression of matrix metalloproteinase-9 and -2 in pediatric chronic otitis media
      with effusion.
AB  - OBJECTIVE: To evaluate the role of MMP-9 and MMP-2 in pediatric patients with
      middle ear effusion (MEE) and determine the pathogenesis of otitis media with
      effusion (OME) and allergy. METHODS: The MEE samples were collected from 25
      patients with allergy and 20 patients without allergy as a control. The levels of
      MMP-9 and MMP-2 were measured using a commercially available enzyme-linked
      immunosorbent assay (ELISA). The activity of MMP-9 and MMP-2 were measured by
      gelatin-zymography. The Mann-Whitney U-test was used for comparisons between the
      allergy positive and control groups. RESULTS: The level of MMP-9 was
      significantly elevated in MEE from the allergy positive group compared to
      controls. The amount of MMP-9 activity significantly increased in the allergy
      positive group compared to controls. CONCLUSION: MMP-9 and MMP-2 are mediators of
      inflammation in the OME; in addition, MMP-9 may play a significant role in the
      pathophysiology of OME with allergy.

PMID- 16413617
TI  - Indications for surgery in acute mastoiditis and their complications in children.
AB  - OBJECTIVE: To review the clinical charts of 45 paediatric patients treated for
      acute otomastoiditis at the ORL Department of the University of Brescia (Italy)
      between January 1994 and March 2005 and to discuss the diagnostic workup and the
      outcome of treatment. METHODS: Twenty-six males and 19 females were admitted with
      acute mastoiditis and subperiosteal abscess. Thirteen of them (28.9%) presented
      an intracranial complication. Only three of them were not operated upon; one
      received a ventilation tube (VT); all the others underwent a mastoidectomy within
      48-72 h. Twenty out of 32 uncomplicated mastoiditis were treated conservatively
      and the remaining 12 underwent myringotomy+/-VT, associated with a mastoidectomy
      in 9 cases. RESULTS: Antibiotics alone or with VTs achieved a full recovery in 28
      out of 32 uncomplicated cases. Mastoidectomy resolved the disease in 13 patients
      (9 with complications). In severe complications, a canal wall down (CWD) (n=2) or
      an intact canal wall (ICW) mastoidectomy (n=7) were preferred, based on the
      extent of the lesions and the degree of hearing loss. All children recovered
      completely at 1 year follow-up. In the uncomplicated cases that were operated
      upon, the mean hospital stay was 7.8 days (versus 4.3 days for the conservative
      group). In children with intracranial complications the mean hospital stay was
      12.8 days, significantly less than the four non-surgical patients, who remained
      hospitalized for an average of 18 days. CONCLUSION: Acute mastoiditis can fully
      recover with conservative treatment or myringotomy+VTs. Immediate surgical
      treatment is indicated for intracranial complications, if the neurological
      conditions are not critical. A simple mastoidectomy+/-tympanoplasty is warranted
      in: (1) exteriorization, if the child is older than 30 months or >15 kg of
      weight, (2) intracranial complications (combined with a neurosurgical procedure
      as needed) and (3) cholesteatoma or granulation tissue.

PMID- 16413618
TI  - A target on the move: innate and adaptive immune escape strategies of hepatitis C
      virus.
AB  - Obligate intracellular parasites such as the hepatitis C virus (HCV) have to cope
      intensively with immune responses in order to establish persistent infection.
      Powerful antiviral mechanisms of the host act on several levels. The innate
      immune response is able to slow down viral replication and activate cytokines
      which trigger the synthesis of antiviral proteins. The adaptive immune system
      neutralizes virus particles and destroys infected cells. Viruses have therefore
      developed a number of countermeasures to stay moving targets for the immune
      system. Here, we attempt to summarize the current state of research regarding
      innate and adaptive immune responses against HCV and the different escape
      strategies evolved by this virus.

PMID- 16413619
TI  - Tissue distribution and subcellular localization of trace metals in the pond
      snail Lymnaea stagnalis with special reference to the role of lysosomal granules
      in metal sequestration.
AB  - The present study was undertaken to elucidate the cellular mechanisms, which
      govern metal sequestration and detoxification in gastropods. For this purpose the
      pond snail, Lymnaea stagnalis was exposed to environmentally relevant
      concentrations of three species of metals (Al, Zn and Cd) for 30 days and the
      localization and fate of these metals were followed in different tissues of the
      snails. The measurement of relative distribution of metals between tissues
      revealed that the digestive gland and kidney account for most of the accumulated
      metals. Al and Cd (non-essential metals) were redistributed to the digestive
      gland, possibly because of the presence of specific binding entities in the
      digestive glands of the herein species. This study focuses on the role of
      intracellular metal-containing granules on metal sequestration. Three main types
      of granules were identified in the digestive gland cells namely small, green and
      yellow granules. The morphological examination and the progressive accumulation
      of elements within these granules revealed that they are developmental stages
      with the yellow granule being the mature one. The total number of these granules
      was found to be significantly increased upon exposure of the snails to Al only.
      This increase may be a response to the large amount of Al that is accumulated
      through feeding route of this grazing snail. X-ray microanalysis (XRMA) revealed
      that metals were localized in all three types of digestive gland granules. The
      increased amount of ligands (P and S) in the granules may give evidence for their
      role in metal sequestration. Levels of Al and P were positively correlated in the
      digestive gland granules. It is possible that aluminium is bound to phosphorus to
      render it insoluble and so to both immobilize it within the lysosome and to be
      excreted in a highly insoluble form. On the other hand, both Zn and Cd induced
      marked upregulation of S in mature (yellow) granules by 26- and 11-folds,
      respectively. The lysosomal codeposition of S and either Cd or Zn in the
      lysosomal granules in addition to the increase in RER cisternae may indicate that
      the exposure to these metals could induce metallothionein synthesis in the cells.
      The microscopical examinations in the present study revealed that metal
      detoxification from the digestive gland cells may occur via faeces or via basal
      exocytosis towards hemocytes dispersed by the connective tissue in the visceral
      mass. In the kidney, one type of granules, the excretory concretions, was
      identified in the nephrocytes. The significant increase in the number of these
      concretions in the snail L. stagnalis upon exposure to metals may give further
      evidence for their role in metal excretion.

PMID- 16413620
TI  - Activation of lipid catabolism by the water-soluble fraction of petroleum in the
      crustacean Macrobrachium borellii.
AB  - Little is known about the effect of the water-soluble fraction of crude oil (WSF)
      on lipid metabolism in invertebrates. The effect of the WSF on the
      triacylglycerol (TAG) mobilization, fatty acid activation and degradation was
      evaluated in the decapod Macrobrachium borellii, exposing adult and eggs at
      different stages of development for 7 days to a sublethal concentration of WSF.
      Using radioactive tracers, mitochondrial palmitoyl-CoA synthetase (ACS),
      triacylglycerol lipase (TAG-lipase) and fatty acid beta-oxidation system
      activities were assayed. Before studying the effect of WSF, the kinetic
      parameters of ACS were determined in purified mitochondria. Its optimal
      temperature and pH were 32 degrees C and 8.0, respectively, the apparent K(m)
      2.48 micromol l(-1), and its V(max) of 1.93 nmol min(-1) mg protein(-1). These
      kinetic parameters differed significantly from this shrimp's microsomal isoform.
      After 7 days exposure to a sublethal concentration of WSF (0.6 mg/l), changes
      were observed in the enzymatic activity of all enzymes or enzymatic system
      assayed in adult midgut gland as well as in stage 5 eggs, a period of active
      organogenesis. An increase in the mobilization of energy stores was detected as
      early as stage 4, where TAG-lipase activity increased by 27% in exposed eggs. The
      increase was even more marked in exposed eggs at stage 5 where a three-fold rise
      (154%) was determined. Exposed adult shrimp also showed an augmented lipase
      activity by 38%. Fatty acid beta-oxidation increased by 51.0 and 35.5% in midgut
      gland and eggs at stage 5, respectively, but no changes were observed at less
      developed stages. Mitochondrial fatty acid activation by ACS also increased in
      adults and stage 5 eggs by 7.4 and 52.0%, respectively. A similar response of the
      lipid catabolic pathways to WSF contamination in both adult and eggs, suggests
      that the exposure to this pollutant causes an increase in the energy needs of
      this shrimp. When validated by field studies, these catabolic enzymes could be
      employed as early pollution biomarkers.

PMID- 16413621
TI  - Comparative planning evaluation of intensity-modulated radiotherapy techniques
      for complex lung cancer cases.
AB  - BACKGROUND AND PURPOSE: Lung cancer treatment can be one of the most challenging
      fields in radiotherapy. The aim of the present study was to compare different
      modalities of radiation delivery based on a balanced scoring scheme for target
      coverage and normal tissue avoidance. PATIENTS AND METHODS: Treatment plans were
      developed for 15 patients with stage III inoperable non-small cell lung cancer
      using 3D conformal technique and intensity-modulated radiotherapy (IMRT).
      Elective nodal irradiation was included for all cases to create the most
      challenging scenarios with large target volumes. A 2 cm margin was used around
      the gross tumour volume (GTV) to generate PTV2 and 1cm margin around elective
      nodes for PTV1 resulting in PTV1 volumes larger than 1000 cm(3) in 13 of the 15
      patients. 3D conformal and IMRT plans were generated on a commercial treatment
      planning system (TheraPlan Plus, Nucletron) with various combinations of beam
      energies and gantry angles. A 'dose quality factor' (DQF) was introduced to
      correlate the plan quality with patient specific parameters. RESULTS: A good
      correlation was found between the quality of the plans and the overlap between
      PTV1 and lungs. The patient feature factor (PFF), which is a product of several
      pertinent characteristics, was introduced to facilitate the choice of a
      particular technique for a particular patient. CONCLUSIONS: This approach may
      allow the evaluation of different treatment options prior to actual planning,
      subject to validation in larger prospective data sets.

PMID- 16413622
TI  - From IMRT to IGRT: frontierland or neverland?
AB  - The recent enthusiasm for real-time image guidance in radiotherapy (IGRT) is in
      part due to the commercial availability of advanced on-line imaging technologies.
      Perhaps more important than its potential to improve conventional radiotherapy,
      IGRT may lead to a paradigm shift in facilitating hypo-fractionated or single
      dose treatment. However, there are uncertainty regarding features and approaches
      of competing IGRT systems and as to whether a sub-set of the features of an ideal
      IGRT system would suffice for specific disease sites and clinical applications.
      Clinical studies are necessary for the quantification of benefit needed for
      evidence-based medicine.

PMID- 16413624
TI  - The influence of stimulus duration on odor perception.
AB  - Although different parameters are known to alter the shape of olfactory event
      related potentials (ERP), ERP parameters are generally thought to be independent
      from stimulus duration. Evidence from recent studies investigating trigeminal ERP
      indicates that this may not be true. Aim of the present study was to investigate
      the relationship of stimulus duration and ERP. A total of 20 young healthy
      subjects participated. Subjects were investigated on 5 occasions on 5 different
      days. ERP were recorded to olfactory stimuli of two different concentrations and
      3 different durations (100 ms, 200 ms, 300 ms). In two sessions olfactory ERP to
      PEA were recorded, in another two sessions H2S was applied. During the same
      sessions, intensity ratings were recorded. In the fifth session, subjects were
      asked to rate the duration of H2S stimuli and PEA stimuli. Whereas at weak
      stimulus concentrations no effect of stimulus duration could be observed, there
      was a clear effect of "duration" in ERP amplitudes following stimuli with higher
      concentrations: the longer the stimulus duration the larger the ERP amplitudes.
      No effect was found on ERP latencies. With regard to intensity ratings, strong
      stimuli and longer lasting stimuli lead to higher ratings. Similarly, ratings of
      stimulus duration were dependent from stimulus concentration and stimulus
      duration. Results of the present study showed that similar to trigeminal ERP,
      information about stimulus duration is encoded in olfactory ERP, mainly in
      amplitudes.

PMID- 16413623
TI  - Feasibility study using a Ni-Ti stent and electronic portal imaging to localize
      the prostate during radiotherapy.
AB  - BACKGROUND AND PURPOSE: A new method for localization of the prostate during
      external beam radiotherapy is presented. The method is based on insertion of a
      thermo-expandable Ni-Ti stent. The stent is originally developed for treatment of
      bladder outlet obstruction caused by benign hyperplasia. The radiological
      properties of the stent are used for precise prostate localization during
      treatment using electronic portal images. PATIENTS AND METHODS: Patients referred
      for intended curative radiotherapy and having a length of their prostatic urethra
      in the range from 25 to 65 mm were included. Pairs of isocentric orthogonal
      portal images were used to determine the 3D position at eight different treatment
      sessions for each patient. RESULTS: Fourteen patients were enrolled in the study.
      The data obtained demonstrated that the stent position was representative of the
      prostate location. The stent may also improve delineation of the prostate GTV,
      and prevent obstruction of bladder outlet during treatment. Precision in
      localization of the stent was less than 1 mm. Random errors in stent position
      were left-right 1.6 mm, cranial-caudal 2.2 mm and anterior-posterior 3.2 mm. In
      four of 14 patients a dislocation of the stent to the bladder occurred.
      Dislocation only occurred in patients with length of prostatic urethra less than
      40 mm. CONCLUSIONS: A new method for radiological high precision localization of
      the prostate during radiotherapy is presented. The method is based on insertion
      of a standard Ni-Ti thermo-expandable stent, designed for treatment of benign
      prostate hyperplasia.

PMID- 16413625
TI  - Epstein-Barr virus (EBV) infection and p53 protein expression in gastric
      carcinoma.
AB  - In the presented studies p53 protein expression was evaluated in samples of
      gastric carcinoma originating from 32 selected adult patients (with documented
      diagnosis of adenocarcinoma of the stomach and without the presence of
      Helicobacter pylori infection). Among the patients 14 individuals carried EBV
      positive gastric carcinoma (group 1) while the 18 remaining patients carried EBV
      negative gastric carcinoma (group 2). EBV infection was detected testing the
      tissue material for the presence of EBER by RNA in situ hybridization (ISH) and
      testing sera of the patients for EBV-specific antibodies. Expression of p53
      protein was analysed using immunohistochemistry. Presence of p53 protein was
      noted in 9 (64.3%) cases of EBV-positive gastric cancer (group 1) and in 10
      (55.5%) cases of EBV-negative gastric cancer (group 2). No significant
      differences were detected in the frequencies of p53 protein expression in the two
      studied groups. The results permit to conclude that abnormalities in p53 in
      gastric cancer are independent of EBV infection, even if EBV may participate in
      development of the tumour.

PMID- 16413626
TI  - Activities of membrane bound phosphatases, transaminases and mitochondrial
      enzymes in white spot syndrome virus infected tissues of Fenneropenaeus indicus.
AB  - Disease caused by viruses, especially white spot syndrome virus (WSSV), present
      the greatest challenge to shrimp aquaculture worldwide. Massive tissue
      disintegration occurs in WSSV-infected ectodermal and mesodermal tissues of
      penaeid shrimp. The activities of membrane bound phosphatases (Na(+)K(+)ATPase,
      Ca(2+)ATPase, Mg(2+)ATPase and Total ATPase), transaminases (alanine transaminase
      (ALT) and aspartate transaminase (AST)) and mitochondrial enzymes (isocitrate
      dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH),
      alpha-ketoglutarate dehydrogenase (KGDH), NADH dehydrogenase, cytochrome C
      oxidase) in WSSV-infected tissues (hemolymph, hepatopancreas, gills and muscle)
      of Fenneropenaeus indicus were determined at intervals after WSSV infection (0,
      24, 48, 72 and after 72 h (moribund)). The activities of phosphatases,
      transaminases and mitochondrial enzymes in healthy as compared with WSSV-infected
      hemolymph, hepatopancreas, gills and muscle showed marked divergence throughout
      the course of infection. WSSV infected hemolymph, hepatopancreas, gills and
      muscle exhibited significantly reduced activity of membrane bound phosphatases
      compared with the uninfected animals. Inactivation of these enzymes may occur due
      to increased production of free radicals, that cause conformational change by
      oxidation of 'SH' groups present at the active site. Significantly marked
      elevation in the activities of transaminases (ALT and AST) was observed in WSSV
      infected hemolymph, hepatopancreas, gills and muscle compared to the uninfected
      tissues. This may be due to leakage of these enzymes from the damaged tissues.
      The activities of mitochondrial enzymes in WSSV-infected tissues were
      significantly decreased compared to the activities in uninfected animals. WSSV
      infected animals showed reduced feeding that may have led to decreased oxidation
      of glucose via the TCA cycle. Excessive production of free radicals in WSSV
      infected animals may have affected aerobic oxidation leading to lower production
      of ATP. It is concluded that membrane dynamics play a major role in the
      pathogenesis of WSSV infection.

PMID- 16413627
TI  - HIV-1-mediated syncytium formation promotes cell-to-cell transfer of Tax protein
      and HTLV-I gene expression.
AB  - An important increase in luciferase activity was detected following co-culture of
      Jurkat T cells transiently transfected with an HTLV-I-LTR-driven reporter
      construct with HIV-1- and HTLV-I-infected cells. Production of infectious HTLV-I
      and expression of the HTLV-I envelope were not required for this HIV-1-dependent
      induction while it was severely hampered by anti-gp120 and anti-CD4 antibodies.
      The HTLV-I Tax protein and the TRE1 repeats were found to be necessary for the
      HIV-1-mediated enhancement of HTLV-I LTR activity in the co-culture assay. As
      these results suggested triple fusion events involving all three cell types and
      the intracellular transfer of Tax, we labelled each cell line with a distinct
      fluorescent probe. Through confocal microscopy, a number of resulting syncytia
      and cell clusters were indeed observed to be positive for all three probes. We
      are proposing a model in which HIV-1-mediated syncytium formation between HIV-1-
      and HTLV-I-infected cells and uninfected T cells forms a "bridge" or "tunnel"
      through which Tax from the HTLV-I-infected cells can diffuse and activate HTLV-I
      LTR transcription.

PMID- 16413628
TI  - Chronic blockade of the angiotensin II receptor has a differential effect on
      adipose and vascular PAI-1 in OLETF rats.
AB  - Angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1) are expressed
      in both vascular and adipose tissues. Angiotensin II (AG II) has an adipogenic
      effect and increases PAI-1 expression. To evaluate the chronic effects of AG II
      type 1 receptor (AT(1)R) antagonism on adipose mass and PAI-1 expression in
      vascular and adipose tissues, losartan (30mg/kg/day) was administered to Otsuka
      Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, for 20
      weeks. Adipose mass and regional fat distribution in the abdomen did not change
      after chronic AT(1)R antagonism in OLETF rats. AGT and PAI-1 mRNA expressions in
      adipose tissue of OLETF rats were significantly increased compared with Long
      Evans Tokushima Otsuka (LETO) rats, the normal control. Chronic losartan therapy
      further increased the level of adipose AGT in OLETF rats, but did not affect the
      level of adipose PAI-1 mRNA. In contrast, aortic PAI-1 expression in OLETF rats
      was attenuated by chronic losartan therapy. Our results have two implications.
      First, adipose tissue may be an important source of AG II in metabolic syndrome
      even after chronic losartan therapy. Second, chronic AT(1)R antagonism with
      losartan causes differential effects on vascular and adipose PAI-1 expression.

PMID- 16413629
TI  - On A1c and its dependence on PG level.

PMID- 16413630
TI  - Greek medical students' career choices indicate strong tendency towards
      specialization and training abroad.
AB  - The aim of the study was to investigate the career choices, location preferences
      and criteria among medical students in Greece. We applied a questionnaire-based
      analysis using a sample of 591 students of four out of seven Greek Medical
      Schools. The sample included students of all academic years. The vast majority of
      students wish to specialize (97.6%), while general practice gathered a very low
      percentage (1.7%). The scientific challenge (61.4%) and interaction with patients
      (60.6%) seem to be the major influencing factors for most of the students'
      specialty preferences, whilst less common variables influencing career choice are
      the high demand/supply ratio for certain health services (40.4%), the income
      potential (31.4%), the active tempo (26.2%) and prestige (15%). 70.3% of those
      asked consider the possibility of specializing abroad. The low concern of Greek
      medical students for general practice reveals today's drastic deficiency in Greek
      primary health care. Such a situation will escalate, unless targeted strategies
      to produce more general practitioners are adopted. Furthermore, the results
      reflect a lower education and organizing level urging students to specialize
      abroad. The National Health System (NHS) should be reformed towards a
      rationalistic distribution of the medical specialties and medical workforce.

PMID- 16413631
TI  - A service based approach for medical image distribution in healthcare Intranets.
AB  - The Digital Imaging and Communications in Medicine (DICOM) protocol is currently
      the ubiquitous standard for the communication of medical images and related data
      within the radiology department. However, seamless image distribution within the
      healthcare enterprise and especially with research and educational information
      systems is still hard to achieve, as software developers of such third-party
      applications have to go through the rather cumbersome task of adapting the DICOM
      communication model and implementing the DICOM protocol. This paper gives a brief
      outline of current trends in medical image distribution in the healthcare
      enterprise, and proposes a new technological approach for distributing DICOM
      images and related data through commonplace Internet technologies, based on the
      emerging web services software paradigm. In particular, the paper describes the
      DICOM Image Management (DIM) web service which acts as a facade for conventional
      DICOM sources allowing DICOM image data and related information, to be
      transformed into XML documents encapsulated in SOAP messages, enabling
      integration at the application level through general purpose standardized web
      technologies. Implementation issues are discussed and a demonstration of engaging
      the DIM web service is included.

PMID- 16413632
TI  - Integral-based identification of patient specific parameters for a minimal
      cardiac model.
AB  - A minimal cardiac model has been developed which accurately captures the
      essential dynamics of the cardiovascular system (CVS). However, identifying
      patient specific parameters with the limited measurements often available,
      hinders the clinical application of the model for diagnosis and therapy
      selection. This paper presents an integral-based parameter identification method
      for fast, accurate identification of patient specific parameters using limited
      measured data. The integral method turns a previously non-linear and non-convex
      optimization problem into a linear and convex identification problem. The model
      includes ventricular interaction and physiological valve dynamics. A healthy
      human state and four disease states, valvular stenosis, pulmonary embolism,
      cardiogenic shock and septic shock are used to test the method. Parameters for
      the healthy and disease states are accurately identified using only discretized
      flows into and out of the two cardiac chambers, the minimum and maximum volumes
      of the left and right ventricles, and the pressure waveforms through the aorta
      and pulmonary artery. These input values can be readily obtained non-invasively
      using echo-cardiography and ultra-sound, or invasively via catheters that are
      often used in Intensive Care. The method enables rapid identification of model
      parameters to match a particular patient condition in clinical real time (3-5
      min) to within a mean value of 4-10% in the presence of 5-15% uniformly
      distributed measurement noise. The specific changes made to simulate each disease
      state are correctly identified in each case to within 10% without false
      identification of any other patient specific parameters. Clinically, the
      resulting patient specific model can then be used to assist medical staff in
      understanding, diagnosis and treatment selection.

PMID- 16413633
TI  - Recursive versus sequential multiple error measures reduction: a curve
      simplification approach to ECG data compression.
AB  - Previous time domain compression methods have been tackled by sequential one
      point at a time sub-optimal selection strategies running in approximately O(N) or
      all points at a time optimal strategies running in approximately O(N3) temporal
      complexities. Yet basically, the selected dominant points (DPs) are locally only
      significant in these methods, which may lead to inaccurate reconstruction or even
      loss of clinical data. Alternatively, the recursive one point at a time selection
      strategy, through different variants of the Douglas-Peucker line simplification
      algorithm, computes globally significant DPs for an approximately O(N.log2(N))
      temporal complexity. We illustrate that the recursive strategy performs
      numerically almost two times better than the sequential one. The piecewise linear
      approximation of the input ECG is formally expressed as a curve simplification
      problem, through reduction of the Hausdorff error measure. We also illustrate
      that reduction of two error measures performs better than reduction of one error
      measure. An additional compression option is proposed in the case of the
      recursive strategy through simplification of the sorted distances associated to
      the selected set of points. The outcome is a compression algorithm that yields
      compression ratios ranging from 8:1 to 22:1 for a perceptually good
      reconstruction quality and near linear execution time. The tests have been
      conducted on the MIT-BIH public ECG database. Results show that the proposed
      recursive algorithm is an excellent compromise on compression ratio -
      computational time - reconstruction quality.

PMID- 16413634
TI  - Partial and full agonism in endomorphin derivatives: comparison by null and
      operational model.
AB  - The partial mu-opioid receptor pool inactivation strategy in isolated mouse vas
      deferens was used to determine partial agonism of endomorphins and their analogs
      (endomorphin-1-ol, 2',6'-dimethyltyrosine (Dmt)-endomorphin-1, endomorphin-2-ol
      and (D-Met2)-endomorphin-2) using morphine, normorphine, morphiceptin, (D
      Ala2,MePhe4,Gly5-ol)-enkephalin (DAMGO) and its amide (DAMGA) as reference opioid
      agonists. Agonist affinities (KA) and efficacies were assessed both by the "null"
      and the "operational" method. The KA values determined by the two methods
      correlated significantly with each other and also with the displacing potencies
      against 3H-naloxone in the receptor binding assay in the presence of Na+. DAMGO
      and DAMGA were full agonist prototypes, morphine, endomorphin-1, endomorphin-1
      ol, Dmt-endomorphin-1, endomorphin-2-ol and (D-Met2)-endomorphin-2 were found by
      both methods to be partial agonists whereas the parameters for normorphine,
      morphiceptin and endomorphin-2 were intermediate.

PMID- 16413635
TI  - Synthesis and biological evaluation of modified acridines: the effect of N- and O
      substituent in the nitrogenated ring on antitumor activity.
AB  - A series of new acridines has been prepared by cyclodehydration of N-(2,3-dihydro
      1,4-benzodioxin-6-yl)anthranilic acid in acidic media following classical
      procedures. All these compounds have in common a dioxygenated ring fused to the
      acridine. The tetracyclic system possesses a linear or angular structure formed
      by intramolecular cyclisation. The last ring and the substituent of the system
      modify, in an interesting way, the antitumor activity of acridines. Several of
      the studied compounds displayed significant cytotoxic activity (inhibition of
      L1210 and HT-29 cell proliferation). The most cytotoxic compound 13a, shows more
      activity than m-AMSA in inhibiting L1210 and HT-29 cell proliferation and this
      compound has been selected as a development candidate for further evaluation. The
      activity results also indicate that the new 11-O-substituted compounds are of
      considerable interest with high levels of cytotoxic activity. The angular or non
      linear dioxinoacridine 10 was equiactive with the linear structure 7. Pentacyclic
      analogues (14 and 15) were more cytotoxic than the tetracyclic compounds (up to
      twofold).

PMID- 16413636
TI  - [The cochlea in Fabry disease: a sensorineural hearing loss model of vascular
      origin?].
AB  - PURPOSE: Fabry disease is an inborn error of metabolism due to a deficient
      activity of the lysosomal enzyme alpha-galactosidase A. The enzyme defect leads
      to the systemic accumulation of neutral glycosphingolipids in tissues, mainly in
      the vascular endothelium. STRONG POINT: The aim of this paper is to present a
      review of the auditory manifestations in Fabry disease, and to discuss hypothesis
      on the vascular origin of deafness. PERSPECTIVES: Sensorineural hearing loss in
      Fabry disease could be the first documented vascular pathology of the inner ear.

PMID- 16413637
TI  - [Portal vein thrombosis associated with acute cytomegalovirus infection in an
      immunocompetent patient].

PMID- 16413638
TI  - [Subcutaneous calcifications in systemic lupus erythematosus].

PMID- 16413639
TI  - Helping student nurses to identify and respond to the psychological needs of
      physically ill patients: implications for curriculum design.
AB  - It is universally accepted that nursing practice is predicated upon the notion of
      holistic care, in that nurses need to address not only the physical needs of ill
      patients but also their psychological, social, spiritual, and environmental
      needs. However, there is considerable evidence to suggest that nurses often
      inadequately identify and respond to patients' psychological needs, sometimes
      with adverse consequences for physical health and recovery. This may be because
      they do not fully understand the concept of psychological care, or have been
      inadequately prepared or educated to deliver it in practice. Following a summary
      of relevant literature and an overview of findings from a larger study of the
      nature and experience of psychological caregiving, this paper discusses specific
      findings on preparing nurses for their psychological caregiving role. The paper
      proposes a curriculum framework designed to enhance awareness, knowledge, and
      skill in effective psychological caregiving in nursing practice, to the ultimate
      benefit of physically ill patients. For the purposes of this paper, psychological
      care is taken to mean one element of the broader concept of care, rather than
      being synonymous with it.

PMID- 16413641
TI  - Optimization of an effective extraction procedure for the analysis of
      microcystins in soils and lake sediments.
AB  - Microcystin analysis in sediments and soils is considered very difficult due to
      low recovery for extraction. This is the primary limiting factor for
      understanding the fate of toxins in the interface between water and sediment in
      both the aquatic ecosystem as well as in soils. In the present study, a wide
      range of extraction solvents were evaluated over a wide range of pH, extraction
      approaches and equilibration time to optimize an effective extraction procedure
      for the analysis of microcystins in soils and lake sediments. The number of
      extractions required and acids in extraction solutions were also studied. In this
      procedure, EDTA-sodium pyrophosphate solution was selected as an extraction
      solvent based on the adsorption mechanism study. The optimized procedure proved
      to be highly efficient and achieved over 90% recovery. Finally, the developed
      procedure was applied to field soil and sediment sample collected from Chinese
      lakes during bloom seasons and microcystins were determined in six of ten
      samples.

PMID- 16413640
TI  - Antimicrobial-resistant patterns of Escherichia coli and Salmonella strains in
      the aquatic Lebanese environments.
AB  - This study is the first to be conducted in Lebanon on the isolation and molecular
      characterization and the antimicrobial resistance profile of environmental
      pathogenic bacterial strains. Fifty-seven samples of seawater, sediment, crab,
      and fresh water were collected during the spring and summer seasons of 2003. The
      isolation of Escherichia coli and Salmonella using appropriate selective media
      revealed that 94.7% of the tested samples were contaminated with one or both of
      the tested bacteria. The polymerase chain reaction (PCR) was then used to
      identify the species of both bacteria using various sets of primers. Many
      pathogenic E. coli isolates were detected by PCR out of which two were identified
      as O157:H7 E. coli. Similarly, the species of many of the Salmonella isolates was
      molecularly identified. The confirmed isolates of Salmonella and E. coli were
      then tested using the disk diffusion method for their susceptibility to four
      different antimicrobials revealing high rates of antimicrobial resistance.

PMID- 16413642
TI  - Spatio-temporal variation of element accumulation by Moehringia trinervia in a
      polluted forest ecosystem (South Poland).
AB  - The aim of this study was to identify factors affecting accumulation of elements
      by Moehringia trinervia (L.) Clairv. in a forest ecosystem impacted by long-term
      inflow of air pollution. The concentrations of N, S, Ca, K, Mg, Cd, Cu, Fe, Pb
      and Zn were determined in plants collected in 1999. In addition, Cd, Cu, Pb and
      Zn content was compared with measurements from 1984. Soil properties and bulk
      precipitation chemistry were used as explaining variables. The amount of heavy
      metals accumulated by M. trinervia depended on the magnitude of industrial
      emissions, but only Cu and Pb concentrations were clearly related to the distance
      from the pollution sources. The spatial distribution of Fe content was shaped by
      habitat conditions, whereas the distributions of Cd and Zn content were
      unexplained. Among the macronutrients, only Mg uptake was affected by
      environmental properties: it was lower under high concentrations of soil Cd and
      Zn.

PMID- 16413643
TI  - Inhaled formaldehyde: evaluation of sensory irritation in relation to
      carcinogenicity.
AB  - OBJECTIVES: The critical health effects of formaldehyde exposure include sensory
      irritation and the potential to induce tumours in the upper respiratory tract. In
      literature, a concentration as low as 0.24 ppm has been reported to be irritating
      to the respiratory tract in humans. Nasal tumour-inducing levels in experimental
      animals seem to be 1-2 orders of magnitude larger. In this paper, the
      subjectively measured sensory irritation threshold levels in humans are discussed
      in line with findings obtained in animal experiments. In addition, a Benchmark
      dose (BMD) analysis of sensory irritation was used to estimate response
      incidences at different formaldehyde concentrations. METHODS: Data on respiratory
      irritation and carcinogenicity of formaldehyde were retrieved from public
      literature and discussed. BMD analysis was carried out on human volunteer studies
      using the US-EPA BMD software. RESULTS: Subjective measures of irritation were
      the major data found in humans to examine sensory (eye and nasal) irritation;
      only one study reported objectively measured eye irritation. On a normalized
      scale, mild/slight eye irritation was observed at levels 1 ppm, and mild/slight
      respiratory tract irritation at levels 2 ppm. With the BMD software, it was
      estimated that at a level of 1 ppm, only 9.5% of healthy volunteers experience
      'moderate' (i.e., annoying) eye irritation (95% upper confidence limit). An
      important factor modulating the reported levels of irritation and health symptoms
      most probably includes the perception of odour intensity. In several studies, the
      0-ppm control condition was missing. From the results of the long-term inhalation
      toxicity studies in experimental animals, a level of 1 ppm formaldehyde has been
      considered a NOAEL for nasal injury. CONCLUSIONS: Sensory irritation is first
      observed at levels of 1 ppm and higher. From both human and animal studies, it
      was concluded that at airborne levels for which the prevalence of sensory
      irritation is minimal both in incidence and degree (i.e., <1 ppm), risks of
      respiratory tract cancer are considered to be negligibly low.

PMID- 16413644
TI  - Meaning-making intervention during breast or colorectal cancer treatment improves
      self-esteem, optimism, and self-efficacy.
AB  - Existential issues often accompany a diagnosis of cancer and remain one aspect of
      psychosocial oncology care for which there is a need for focused, empirically
      tested interventions. This study examined the efficacy of a novel psychological
      intervention specifically designed to address existential issues through the use
      of meaning-making coping strategies on psychological adjustment to cancer. Eighty
      two breast or colorectal cancer patients were randomly chosen to receive routine
      care (control group) or up to four sessions that explored the meaning of the
      emotional responses and cognitive appraisals of each individual's cancer
      experience within the context of past life events and future goals (experimental
      group). This paper reports the results from 74 patients who completed and
      returned pre- and post-test measures for self-esteem, optimism, and self
      efficacy. After controlling for baseline scores, the experimental group
      participants demonstrated significantly higher levels of self-esteem, optimism,
      and self-efficacy compared to the control group. The results are discussed in
      light of the theoretical and clinical implications of meaning-making coping in
      the context of stress and illness.

PMID- 16413645
TI  - Putting at risk what we know: reflecting on the drug-using subject in harm
      reduction and its political implications.
AB  - This paper provides a poststructuralist analysis of the cultural inscription of
      drug-using subjects in the neo-liberal discourses of contemporary harm reduction.
      We argue that although neo-liberal discourses downplay material constraints on
      individual human agency, divert policy and practice away from structural issues,
      limit the conception of effective strategies for harm reduction and ignore
      alternative formulations of the subject, they are also potentially empowering for
      drug users. Approximating the neo-liberal subject offers political benefits in
      terms of recognition, trust and legitimation, even as those values assume and
      reproduce understandings of behaviour, thought and sociality that fit only poorly
      the realities faced by many drug users. We explore this dilemma and consider
      three available directions in formulating the subject of harm reduction: (1)
      embracing the neo-liberal subject; (2) employing a more contextualised version of
      the neo-liberal subject; and (3) adopting alternative notions of subjectivity,
      extending the critique of the neo-liberal subject to all citizens, not solely
      drug users. To clarify some of these issues surrounding this strategic process,
      the paper considers another field in which struggles over the nature of the
      subject have been conducted--feminism. The intention is not to resolve the
      question of the most appropriate subject for harm reduction, but to sketch the
      political consequences of adopting particular models of the subject as a stimulus
      to further discussion and debate.

PMID- 16413646
TI  - Effects of co-administration of bupropion and nicotinic agonists on the elevated
      plus-maze test in mice.
AB  - There is evidence that the cholinergic nicotinic system is involved in the
      modulation of anxiety. Anxiolytic and anxiogenic effects of nicotine agonists
      have been reported in mice. Bupropion is an antidepressant drug which may
      alleviate some symptoms of nicotine withdrawal, although its effects on anxiety
      are not clear. It has been suggested that the interaction between bupropion and
      nicotinic mechanisms could be complex. The aim of the present study was to
      investigate acute effects of co-administration of bupropion and nicotinic
      agonists on the elevated plus-maze test in NMRI mice. Effects of nicotine,
      lobeline, and cytisine (0.35 and 0.175 mg/kg), administered alone or combined
      with bupropion (20 mg/kg) were tested in the plus-maze. Results indicated that
      nicotine (0.35 mg/kg) decreased number and percentage of entries and time spent
      in open arms, and increased percentage of protected stretched attend posture.
      Bupropion (20 mg/kg) plus lobeline (0.175 mg/kg) increased percentage of time
      spent in open arms, without altering total or closed arm entries. Our findings
      suggest that the highest dose of nicotine induces anxiogenic effects, which are
      counteracted when co-administered with bupropion. The combination of bupropion
      with a low dose of lobeline seems to have an anxiolytic profile in the
      conventional parameters of the plus-maze, although ethological measures do not
      support it clearly.

PMID- 16413647
TI  - Are placebo-controlled trials still important for obsessive compulsive disorder?
AB  - The use of placebos as reference agents in randomised controlled trials for
      psychiatric disorders has come under question for ethical reasons. Alternative
      methods for validating the efficacy of new treatments exist, but may not be as
      reliable as placebo. In this paper we examine arguments for and against the
      ongoing use of placebo agents in the development of new treatments for obsessive
      compulsive disorder in the context of evidence from randomised controlled trials.

PMID- 16413648
TI  - Identification of human liver mitochondrial aldehyde dehydrogenase as a potential
      target for microcystin-LR.
AB  - Microcystins (MCs) are hepatotoxins produced by a variety of freshwater
      cyanobacteria. The toxicity of these hepatotoxins is a severe health issue for
      both humans and livestock; MCs have been implicated in the development of liver
      cancer, necrosis, and even deadly intrahepatic bleeding. Microcystin-LR (MC-LR)
      is the MC variant most commonly encountered in a contaminated aquatic system.
      Thus far, MC-LR has only been shown to target the serine/threonine protein
      phosphatases 1 and 2A (PP1 and PP2A) and it is still unknown whether MC-LR can
      bind and inhibit any other protein targets inside the cell. To find potential MC
      LR targets, we screened a phage display library for peptide ligands that
      specifically recognize MC-LR. Using these peptide sequences as guides, we
      performed a series of bioinformatics analyses revealing that MC-LR binds human
      liver aldehyde dehydrogenase 2 (ALDH2) at residues 447-451. We confirmed MC-LR
      binding of ALDH2 via automated docking computation, which yielded results
      matching our experimental and bioinformatics analyses. ALDH2 dysfunction may lead
      to aldehyde-induced reactive oxygen species (ROS) generation and, in turn,
      apoptosis. Therefore, ALDH2 could potentially be a target of MC-LR associated
      with the process of ROS-induced apoptosis. Our current study presents a new
      approach to the study of interactions of biological molecules by combining phage
      display technology with computational methods.

PMID- 16413649
TI  - Human reporter gene assays: transcriptional activity of the androgen receptor is
      modulated by the cellular environment and promoter context.
AB  - The androgen receptor (AR) is a member of the nuclear receptor superfamily and
      mediates the physiological effects of androgens. Androgens are essential for male
      development and disruption of androgen signaling may cause androgen-dependent
      developmental defects and/or tumors. Here we present a comparative analysis of
      various model systems for the investigation of endocrine active compounds in
      human cell lines. We generated reporter plasmids containing androgen response
      elements derived from the human secretory component or the rat probasin genes as
      well as the glucocorticoid consensus response element and compared their
      activities to that of the mouse mammary tumor virus promotor. Additionally, we
      generated an expression plasmid containing the AR cDNA derived from LNCaP cells.
      In 22Rv1 cells transiently transfected with human AR, all reporters displayed a
      dose-dependent, high activity when treated with androgens. Interestingly, the
      potency of testosterone and its metabolite dihydrotestosterone was very low in
      HepG2 but not in 22Rv1 cells, independent of the reporter used. The efficacies of
      the androgens tested were comparable in both cell lines but highly dependent on
      the reporter used. Based on these results, 22Rv1 cells provide a highly sensitive
      in vitro test system to analyze endocrine activities of xenobiotics. Furthermore,
      this study highlights the need to investigate the (anti-) androgenic activity of
      compounds in dependence of the cellular and promoter context.

PMID- 16413650
TI  - Oxidative stress and apoptotic changes in murine splenocytes exposed to cadmium.
AB  - Cadmium being a potent immunotoxicant, affects both humoral and cell mediated
      immunity. However, its effect on spleen is not clearly understood. Hence, to
      delineate the action of Cd, mouse splenic lymphocytes were exposed to Cd (10, 25
      and 50 microM) for 60 min, 1.5, 3, 6 and 18 h. At 6 h, apoptosis was reflected by
      DNA fragmentation, increased sub-G1 population (apoptotic DNA) and apoptotic
      cells (Annexin V binding assay). The early stage markers of apoptosis, i.e.
      decreased mitochondrial membrane potential and caspase-3 activation were observed
      as early as 1.5 h by the highest dose of Cd (50 microM). Significant ROS
      production by 25 and 50 microM Cd at 60 min occurred prior to the lowering of
      mitochondrial membrane potential, suggesting involvement of ROS in causing
      mitochondrial membrane damage. N-acetylcysteine and pyrrolidine dithiocarbamate
      (thiol antioxidants) lowered the sub-G(1) population, inhibited the ROS
      generation and raised the GSH levels induced by Cd. Buthionine sulfoximine (GSH
      depletor) on the other hand, enhanced the ROS production as well as the sub-G1
      fraction. These results imply that ROS is a critical mediator of Cd-induced
      apoptosis and that cadmium may compromise splenic immune function by accelerating
      apoptosis.

PMID- 16413652
TI  - Effect of reducing frequency of augmented feedback on manual dexterity training
      and its retention.
AB  - OBJECTIVE: The study addressed the impact of the frequency of tutorial-enriched
      augmented visual feedback, provided by a virtual simulation system (DentSim), on
      the skill acquisition for a cavity preparation task in novice dental students.
      METHODS: Thirty-six subjects were assigned to two training groups and a control
      group. The task consisted of a geometrical cross preparation on the lower left
      first molar. All subjects performed a pre-test to assess their basic skill level.
      The training groups received simulation feedback, enriched with tutorial
      information, across acquisition. One group trained under continuous augmented
      feedback, while a second group trained under an intermittent (66% of the time)
      feedback. At both 1-day and 4-month interval, subjects performed a retention test
      to explore learning specific effects. Two transfer tests were added to assess the
      extrapolation of the learned skills to an adjacent molar. All tests were
      performed in the absence of feedback. A control group performed all the tests,
      without preceding training. All preparations were graded by the simulation
      system. RESULTS: The training groups performed similarly across acquisition and
      improved with practice (ANOVA, P<0.001). After 1 day and 4 months of no practice,
      the training groups outperformed the control group on a retention test (ANOVA,
      P<0.001) and transfer test (ANOVA, P<0.001). CONCLUSIONS: Performance and
      learning of a cavity preparation task on a simulation unit was independent of the
      frequency of tutorial-enriched augmented visual feedback within the range tested.
      Training sessions on a simulation unit could be alternated with training sessions
      in the traditional phantom head laboratory.

PMID- 16413651
TI  - Prolonged exposure to arecoline arrested human KB epithelial cell growth:
      regulatory mechanisms of cell cycle and apoptosis.
AB  - Arecoline, the main areca alkaloid in betel quid (BQ), is reported to have
      cytotoxic, genotoxic, and mutagenic effects in various cells. It shows strong
      correlation to the incidence of oral submucous fibrosis, leukoplakia, and oral
      cancer. To clarify the role of arecoline in BQ-induced carcinogenesis, primary
      human gingival keratinocyes (GK) and human KB epithelial cells were used for
      studying the molecular mechanisms of arecoline-mediated cell cycle deregulation
      for comparison. After 24 h of exposure, arecoline (0.2-0.8 mM) inhibited KB cell
      growth in a dose- and time-dependent manner with a reduction in cell number by 27
      37 and 37-58%, respectively, as determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5
      diphenyl-tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. Incubation
      of KB cells with arecoline (0.1-0.4 mM) caused late-S and G2/M phases' cell cycle
      arrest. Western blot analysis revealed that arecoline induced cyclin Bl, Wee 1,
      and phosphorylated cdc2 protein levels whereas it declined p21 protein expression
      in KB cancer cells. Nevertheless, arecoline induced p21, but decreased cdc2 and
      cyclin B1 protein levels in GK. We demonstrated that higher concentrations of
      arecoline (0.2-1.2 mM) induced both cell necrosis and apoptosis as detected by
      DNA fragmentation and Annexin V-PI staining after long-term (48 h) treatment. Our
      results suggest that differential regulation of S and/or G2/M cell cycle-related
      proteins in the GK and KB cells play a crucial role in different stages of BQ
      mediated carcinogenesis.

PMID- 16413653
TI  - Use of fluorescent compounds in assessing bonded resin-based restorations: a
      literature review.
AB  - OBJECTIVES: This work reviews fundamental concepts involved with fluorescent
      imaging in the dental materials field. DATA: Fluorescent dyes have been widely
      used: incorporated into adhesive system components, placed in the pulp chamber
      and allowed to diffuse toward the restorative interface, as well as used as a
      visible tracer in microleakage tests. CONCLUSIONS: Although use of fluorescent
      imaging has substantially contributed to the existing knowledge base, there is no
      standardized methodology used, and as a result, interpretation of study results
      as well as comparison of results among studies remains questionable.

PMID- 16413654
TI  - EMS system in Croatia.
AB  - This article describes the features of Croatia's emergency medical services. Pre
      hospital emergency medical services (EMS) access, regional differences and the
      main features of the service are described. EMS personnel education and skill
      levels are also discussed. The author offers a critical analysis of the current
      status and proposals for the future development of emergency medicine in Croatia
      based on changes in organisation and education.

PMID- 16413655
TI  - Behavioural and electrophysiological measures of task switching during single and
      mixed-task conditions.
AB  - In order to understand how the brain prepares for and executes a switch in task
      demand, we measured reaction time (RT), accuracy, and event-related brain
      potentials associated with performance in single and mixed-task blocks using a
      cued design. Our results show that trials which repeat in a mixed-task block
      (repeat trials) were more demanding than trials which repeated in a single-task
      block, as reflected by the presence of a RT mixing cost and by the presence of a
      smaller target-locked positivity (P3b) on repeat trials. Within a mixed-task
      block, repeat and switch trials also differed, where repeat trials showed
      evidence of greater preparation (larger cue-locked negativity), more efficient
      target processing (larger target-locked P3b), and shorter RTs. In addition, the
      cue-locked negativity difference remained despite equating repeat and switch
      trials on RT, suggesting that this negativity difference is specific to the
      switching process. Our results are discussed in light of existing models of task
      switching.

PMID- 16413656
TI  - Cost-consequence analysis evaluating the use of botulinum neurotoxin-A in
      patients with detrusor overactivity based on clinical outcomes observed at a
      single UK centre.
AB  - OBJECTIVE(S): This study aimed to assess the resource utilisation, health
      benefits and cost-effectiveness of intra-detrusor injections of botulinum
      neurotoxin-A (BoNT/A) in patients with overactive bladder (OAB). METHODS: 101
      patients with urodynamically-proven detrusor overactivity of either neurogenic
      (NDO; n = 63) or idiopathic (IDO; n = 38) origin received intra-detrusor
      injections of 200-300 units of BoNT/A in 20-30 ml saline as part of a research
      protocol. Twenty-nine patients received repeat injections after 7-26 months.
      Symptom severity and urodynamic parameters were assessed at 0, 4 and 16 weeks.
      The cost of therapy was quantified based on the NHS resources used by typical
      patients and was used to calculate the cost-effectiveness of BoNT/A compared with
      standard care from the perspective of the UK NHS. RESULTS: In an intent-to-treat
      analysis, 82% of patients showed a 25% or greater improvement in at least two out
      of five parameters (urinary frequency, urgency, urgency incontinence episodes,
      maximum cystometric capacity and maximum detrusor pressure) four weeks after
      treatment, reducing to 65% after 16 weeks. A 50% or greater improvement in the
      frequency of micturition, urgency or urgency incontinence was seen in 73% of
      patients at four weeks and 54% at 16 weeks. There were no significant differences
      between IDO and NDO patients in the proportion meeting these endpoints. Therapy
      cost pounds 826 per patient, with a cost-effectiveness ratio of pounds 617 per
      patient-year with > or = 25% clinical improvement. CONCLUSION(S): This study
      demonstrates that intra-detrusor BoNT/A is an effective treatment for OAB that is
      highly likely to be cost-effective in both idiopathic and neurogenic disease.

PMID- 16413658
TI  - Varicocelectomy, evidence-based medicine and fallibility.

PMID- 16413657
TI  - Objective and subjective cure rates after trans-obturator tape (OBTAPE) treatment
      of female urinary incontinence.
AB  - OBJECTIVE(S): To evaluate the safety and efficacy of a thermally bonded nonwoven
      polypropylene mesh in a transobturator suburethral tape procedure (OBTAPE),
      Mentor-Porges, Le Plessis Robinson, France) for women with stress urinary
      incontinence. METHODS: Between January 2003 and January 2005, 129 consecutive
      women (mean age 57.2 years) underwent OBTAPE) in two academic centers. All the
      patients had stress urinary incontinence preoperatively. Detrusor instability was
      ruled out by cystometry. The women were evaluated 1, 6 and 12 months
      postoperatively. The objective cure rate was evaluated by clinical examination
      and the subjective cure rate was assessed using the KHQ and BFLUTS questionnaire.
      RESULTS: Mean follow-up was 17.2+/-4.7 months (range 4 to 28 months). The
      objective and subjective cure rates were respectively 89.9% and 77.5%. Most of
      the patients received general anesthesia (85.3%). Urinary retention was observed
      in two women (1.5%), necessitating tape adjustment. Voiding difficulties were
      observed in 7 cases (5.4%) necessitating intermittent self-catheterization for
      4.2+/-2.4 days (range 1 to 7 days). Seven patients developed vaginal erosion (one
      with vaginal extrusion, and two with an obturator abscess). Complete mesh removal
      was necessary in 6 patients, four of whom had recurrent stress urinary
      incontinence. CONCLUSIONS: Our results suggest that the OBTAPE) is an effective
      treatment for women with stress urinary incontinence. However, vaginal mesh
      erosion occurred in 6.2% of women, and this implies the need for careful follow
      up.

PMID- 16413659
TI  - Watchful waiting policy in recurrent Ta G1 bladder tumors.
AB  - OBJECTIVE: To determine the outcome of a watchful waiting policy in patients
      suffering from small, recurrent, papillary bladder tumors. METHODS: Watchful
      waiting has been considered an option when a small (<10 mm) papillary,
      asymptomatic tumor with negative urinary cytology was found on follow-up
      cystoscopy in patients who had previous resection(s) of superficial, low-grade
      (Ta) bladder tumor(s). The watchful waiting protocol included cystoscopy and
      urinary cytology every 3 months for 2 years (and then every 6 months).
      Surveillance was stopped if the patient had developed either symptoms related to
      the tumor or positive cytology, or if there had been a significant alteration in
      tumor morphology or size. RESULTS: Thirty-eight watchful waiting periods were
      documented in 28 patients (mean age 67.7 years). Mean period length was 13.5
      months (SD 14.4 months; range 3-60 months). Thirty periods were terminated with
      tumor resection. The main reasons for termination of surveillance were the
      appearance of additional tumors (19 patients) and excessive tumor growth (9
      patients). Hematuria indicated tumor removal in only one patient. All resected
      tumors were stage Ta (23 were grade 1, and 7, grade 2). The rate of tumor growth
      during the watchful waiting period depended highly on the tumor's largest
      diameter at the beginning of surveillance. If the initial tumor diameter was
      smaller than 5 mm (32 cases), the tumor growth rate was 4+/-5.1 mm3/mo (mean+/
      SD); if the initial tumor diameter was > or =5 mm (6 cases), the tumor growth
      rate was 870+/-1116 mm3/mo (p < 0.05). CONCLUSIONS: Small, recurrent papillary
      bladder tumors after resection of low-grade Ta tumor(s) pose minimal risk for the
      patient. A watchful waiting policy- without resection of the tumor-may be
      considered in these patients.

PMID- 16413661
TI  - Successful treatment with intradetrusor Botulinum-A toxin for urethral urinary
      leakage (catheter bypassing) in patients with end-staged multiple sclerosis and
      indwelling suprapubic catheters.
AB  - OBJECTIVE: To present the initial results of Botulinum-A toxin (BTA) injection in
      patients with long-standing multiple sclerosis (MS) and urethral leakage of urine
      in spite of indwelling suprapubic catheters (catheter bypassing). METHODS: Study
      of three patients treated with cystoscopic injection of BTA IU (Allergan).
      Telephone interviews were made at four- to six-week intervals. Continence status
      and patient satisfaction were recorded before and after treatment. RESULTS:
      Patient 1 remained dry at 48 weeks post injection. Patient 2 became incontinent
      again after 40 weeks. The third patient was continent when interviewed at 27
      weeks following injection, but died two weeks later. The patients were very
      satisfied with the procedure and there were no complications related to BTA.
      CONCLUSIONS: Intradetrusor BTA injection is a very effective and safe treatment
      for intractable catheter bypassing in patients with neurogenic detrusor
      overactivity.

PMID- 16413660
TI  - The actual value of the surgical margin status as a predictor of disease
      progression in men with early prostate cancer.
AB  - OBJECTIVES: The surgical margin status after radical prostatectomy for prostate
      cancer has long been considered a powerful prognostic factor, as well as an
      important risk factor for local recurrent disease after radical prostatectomy. In
      this study, a critical analysis of the predictive value of the surgical margin
      status was performed. METHODS: A well-described cohort of 281 participants of a
      population-based randomized screening trial who underwent radical prostatectomy
      between 1994 and 2000 was analyzed. Besides pathologic tumor stage, Gleason
      score, percentage of high-grade cancer, and tumor volume, the prognostic value of
      the surgical margin status for disease outcome (prostate-specific antigen [PSA]
      relapse, local recurrence) was statistically evaluated. Specifically, site
      ('apical' or 'circumferential') and extent of surgical margin negativity
      ('negative', or 'close') or positivity ('focal' or 'extensive') was assessed.
      RESULTS: At a median follow-up of 7 yr (range, 5-120 mo), 39 (13.9%) and 7 (2.5%)
      men had biochemical failure (PSA >/=0.1ng/ml), and local relapse, respectively.
      The surgical margin status was positive in 66 (23.5%), with 26 (9.3%) at the
      prostatic apex. The margin status was an independent statistically significant
      risk factor for biochemical relapse, though not for local relapse. Of those with
      positive margins, 22 (33.3%) had PSA relapse and 4 (6.1%) had local recurrence,
      whereas these figures were 17 (7.9%) and 3 (1.4%) for those with a negative
      surgical margin, respectively. The extent of margin positivity was not predictive
      of PSA relapse nor was the site of the surgical margin. CONCLUSIONS: In
      surgically treated prostate cancer, the surgical margin status has, although
      being a statistically significant prognostic factor, only limited predictive
      value for PSA relapse and local recurrent disease. The majority of men with
      (extensive) positive surgical margins will not experience PSA relapse nor local
      disease progression, even in absence of adjuvant radiotherapy. So, cases with a
      positive margin of resection may still be cured, although the procedure in itself
      was not 'radical'.

PMID- 16413662
TI  - Are all alpha-blockers created the same?

PMID- 16413663
TI  - The predictive value of p53, p27(kip1), and alpha-catenin for progression in
      superficial bladder carcinoma.
AB  - OBJECTIVE: The aim of the study was to confirm the predictive value of cell cycle
      regulatory proteins, p53 and p27(kip1), and the cell adhesion complex protein
      alpha-catenin, for progression in patients with superficial bladder carcinoma.
      METHODS: Forty-one patients with progression after primary superficial bladder
      carcinoma were individually matched to patients with nonprogressive superficial
      bladder carcinoma. Matching was done for sex, age, tumor stage and grade,
      concomitant carcinoma in situ (CIS), and duration of follow-up.
      Immunohistochemical analysis of p53, p27(kip1), and alpha-catenin was performed
      on each primary bladder tumor. Analysis for the p53 mutation was done on 41
      bladder tumor samples. Conditional logistic regression analysis was used to
      establish the prognostic value of immunohistochemical p53, p27(kip1), and alpha
      catenin status. RESULTS: The independent odds ratios for progression were 0.3
      (95% confidence interval [CI], 0.1-1.2) for high-risk p27(kip1), 3.4 (95%CI, 0.8
      15.2) for high-risk p53, and 2.5 (95%CI, 0.6-10.3) for high-risk alpha-catenin.
      Combinations of different markers had no synergistic effects. Two p53 mutations
      were found in 21 DNA samples analyzed from nonprogressive tumors (9.5%); 8 of 20
      samples (40%) from progressive tumors showed a p53 mutation. The probability of
      high-risk p53 immunostaining was 5-fold increased in case of mutations in p53.
      The estimated positive predictive value of high-risk p53 or high-risk alpha
      catenin was about 23%. CONCLUSIONS: We confirm that high-risk p53, p53 mutation,
      and alpha-catenin immunohistochemistry do have an additional prognostic value in
      primary bladder carcinoma. However, the clinical value of the investigated
      parameters remains limited.

PMID- 16413664
TI  - The human PC346 xenograft and cell line panel: a model system for prostate cancer
      progression.
AB  - OBJECTIVE: Prostate cancer (PC) model systems that reflect the different disease
      stages are essential for studying the development and progression of PC and for
      testing new treatment modalities. This review summarizes the establishment and
      characterization of the PC346 progression model and compares it to other
      available human PC cell lines and xenografts. METHODS: The PC346 model was
      derived from the transurethral resection of a primary prostate tumor. Tumor
      samples were subcutaneously implanted into athymic mice, which resulted in the
      development of a series of xenografts from which in vitro cell cultures were
      established. RESULTS: The PC346 panel includes sublines with hormone-response
      characteristics that range from androgen-sensitive to androgen-independent (AI)
      growth. In vivo and in vitro selection of androgen-sensitive lines under androgen
      depleted conditions replicated the clinically relevant relapse phenomenon, and
      resulted in a series of modifications in the androgen-receptor (AR) pathway: AR
      mutation, overexpression, and downregulation. CONCLUSIONS: The PC346 panel
      reproduces many biological characteristics of the different phases of clinical PC
      and the most common AR modifications observed in hormone-refractory tumors, being
      a valuable addition to the limited collection of available model systems.

PMID- 16413665
TI  - 2005 update on pathology of prostate biopsies with cancer.
AB  - OBJECTIVE: To review the diagnostic and prognostic importance of pathologic
      findings in prostate biopsies. MATERIALS AND RESULTS: While the primary goal of
      the biopsy is to diagnose prostatic adenocarcinoma, once carcinoma is detected,
      information regarding the type, amount, and grade of cancer forms the cornerstone
      for contemporary management of the patient and for assessment of the potential
      for local cure and the risk for distant metastasis. CONCLUSIONS: The novelty of
      this 2005 update is represented by a detailed morphologic and immunohistochemical
      description of prostatic adenocarcinoma features in biopsies.

PMID- 16413666
TI  - Baseline potency in candidates for bilateral nerve-sparing radical retropubic
      prostatectomy.
AB  - OBJECTIVES: To assess the baseline erectile function (EF) of patients with
      clinically localized prostate cancer (pCa), who are candidates for a bilateral
      nerve-sparing radical retropubic prostatectomy (BNSRRP) to (a) objectively rate
      the preoperative self-reported subjective patient's EF and (b) investigate
      possible correlations between preoperative EF and demographic data and
      comorbidities. MATERIALS AND METHODS: Two-hundred-thirty-four patients, who
      verbally self-reported they were preoperatively fully potent and strongly
      motivated to maintain postoperative EF, underwent a BNSRRP. A comprehensive
      medical and sexual history was obtained on hospital admission the day prior to
      surgery. Subjectively reported potency rate was compared with the scores of the
      International Index of Erectile Function (IIEF). RESULTS: The EF domain of the
      IIEF showed a baseline normal EF in only 43% of the subjects. In contrast, 13%
      had a mild erectile dysfunction (ED), 8% had a mild to moderate ED, 8% complained
      of a moderate ED, and as many as 28% reported severe EF impairment.
      Interestingly, 38% of the patients with severe ED did not attempt any intercourse
      during the last 4 weeks prior to surgery. CONCLUSIONS: A significant proportion
      of patients with clinically localized pCa and self-reported total potency already
      had suffered from ED preoperatively. Incorrect timing of questionnaires
      administration, the potential influence of preoperative patient's psychological
      distress, and the implication of the patient's partner's psychological and sexual
      health may be contributing factors to the contradictory finding. The preoperative
      use of validated questionnaire may help to identify patients who can actually
      expect to regain potency following a BNSRRP.

PMID- 16413667
TI  - Stents for prostatic diseases: any progress after 25 years?

PMID- 16413668
TI  - Treatment of bacterial urinary tract infections: presence and future.
AB  - Bacterial urinary tract infections (UTIs) are frequent infections in the
      outpatient as well as in the nosocomial setting. The stratification into
      uncomplicated and complicated UTIs has proven to be clinically useful. Bacterial
      virulence factors on the one side and the integrity of the host defense
      mechanisms on the other side determine the course of the infection. In
      uncomplicated UTIs Escherichia coli is the leading organism, whereas in
      complicated UTIs the bacterial spectrum is much broader including Gram-negative
      and Gram-positive and often multiresistant organisms. The therapy of
      uncomplicated UTIs is almost exclusively antibacterial, whereas in complicated
      UTIs the complicating factors have to be treated as well. There are two
      predominant aims in the antimicrobial treatment of both uncomplicated and
      complicated UTIs: (i) rapid and effective response to therapy and prevention of
      recurrence of the individual patient treated; (ii) prevention of emergence of
      resistance to antimicrobial chemotherapy in the microbial environment. The main
      drawback of current antibiotic therapies is the emergence and rapid increase of
      antibiotic resistance. To combat this development several strategies can be
      followed. Decrease the amount of antibiotics administered, optimal dosing,
      prevention of infection and development of new antibiotic substances. The aim of
      this review is to highlight the current and to describe future treatment options
      for UTIs.

PMID- 16413669
TI  - New inhibitors of 17beta-hydroxysteroid dehydrogenase type 1.
AB  - The estradiol-synthesizing enzyme 17beta-hydroxysteroid dehydrogenase type 1
      (17betaHSD1) is mainly responsible for the conversion of estrone (E1) to the
      potent estrogen estradiol (E2). It is a key player to control tissue levels of E2
      and is therefore an attractive target in estradiol-dependent diseases like breast
      cancer or endometriosis. We selected a unique non-steroidal pyrimidinone core to
      start a lead optimization program. We optimized this core by modulation of R1-R6.
      Its binding mode at the substrate-binding site of 17betaHSD1 is complex and
      difficult to predict. Nevertheless, some basic structure-activity relationships
      could be identified. In vitro, the most active pyrimidinone derivative showed
      effective inhibition of recombinant human 17betaHSD1 at nanomolar concentrations.
      In intact cells overexpressing the human enzyme, IC50 values in the lower
      micromolar range were determined. Furthermore, the pyrimidinone proved its use in
      vivo by significantly reducing 17betaHSD1-dependent tumor growth in a new nude
      mouse model.

PMID- 16413670
TI  - Insights into sperm cell motility signaling through sNHE and the CatSpers.
AB  - Successful natural reproduction normally requires vigorously motile spermatozoa.
      Using a signal peptide trapping strategy, we identified two new genes, a putative
      sperm Na+/H+ exchanger (sNHE) and the putative cation channel CatSper2, with
      unique and essential roles in sperm motility. Disruption of the sNHE or CatSper2
      genes in mice caused male infertility due to immotile spermatozoa or failed
      motility hyperactivation, respectively, without other apparent abnormalities. The
      immotility phenotype of the sNHE null spermatozoa appears to result from an
      intimate association of sNHE and the atypical adenylyl cyclase (sAC), while a
      failure of calcium entry requiring an apparent CatSper1 and -2 heteromeric ion
      channel correlates with a hyperactivation defect in these null animals. The
      specific expression of sNHE and the CatSpers in spermatozoa and their required
      function in cell motility make them excellent potential targets for the
      development of novel male contraceptives.

PMID- 16413671
TI  - Identification of novel epididymal genes by expression profiling and in silico
      gene discovery.
AB  - We have used both the UniGene RIKEN epididymal EST library and the Affymetrix
      microarray profiling for identifying novel epididymal genes in mouse. The use of
      ESTs is a complementary approach to Affymetrix arrays for identifying novel
      epididymal genes, while only 32% and 28% of ESTs of unknown genes were present in
      the U74v.2Set and MG 430 2.0 version Affymetrix arrays, respectively. As
      expected, the probe set for a notably larger proportion of known genes was
      present in the Affymetrix arrays, and the coverage was greatly improved by the
      newer array version. Furthermore, many genes with more than five ESTs in the
      UniGene library showed variable levels of expression in both versions of the
      Affymetrix arrays. However, both the Affymetrix and EST data correlated well with
      that obtained by quantitative RT-PCR, and thus, we conclude that the findings of
      high EST number but only limited expression in the arrays could be considered as
      false negatives in the Affymetrix arrays.

PMID- 16413672
TI  - Roles of glycodelin in modulating sperm function.
AB  - Glycodelin is a glycoprotein with three well-defined isoforms. They are named as
      glycodelin-S, glycodelin-A and glycodelin-F. The three isoforms have similar
      protein core but different carbohydrate moieties. Glycodelin-S is abundant in the
      human seminal plasma. It suppresses sperm capacitation and in doing so, it
      maintains the spermatozoa in an uncapacitated state before they enter into the
      uterine cavity. Glycodelin-A is abundant in the amniotic fluid. It is also
      secreted from endometrial glands into uterine fluid and is produced by the
      fallopian tube. Glycodelin-A is the first endogenous glycoprotein that was found
      to inhibit the binding of spermatozoa to the zona pellucida. The
      immunosuppressive properties of glycodelin-A suggest that the molecule may
      protect the spermatozoa from immune attack in the maternal reproductive tract.
      Glycodelin-F was first found in the follicular fluid, hence its name. It also
      inhibits spermatozoa-zona pellucida binding. In addition, glycodelin-F suppresses
      progesterone-induced acrosome reaction, and may serve to prevent premature
      acrosome reaction. Preliminary findings suggest possible presence of yet another
      glycodelin isoform in the extracellular matrix of cumulus oophorus. Unlike
      glycodelin-A and -F, it stimulates spermatozoa-zona pellucida binding. In
      summary, different isoforms of glycodelin have different biological roles on
      sperm function, and they act in succession to contribute to the success of
      fertilization.

PMID- 16413673
TI  - Deletion of the DNA/RNA-binding protein MSY2 leads to post-meiotic arrest.
AB  - Y-box proteins are a well-characterized family of nucleic acid binding proteins
      that are expressed from bacteria to human. This review will focus on MSY2, a
      member of the Y-box gene family that is exclusively expressed in male and female
      germ cells. MSY2 is the mouse ortholog of FRGY2, the Xenopus germ cell-specific
      protein and the human germ cell protein, Contrin. MSY2 functions as a co
      activator of transcription in male germ cells and plays an important role in the
      translational repression and storage of both paternal and maternal mRNAs in
      spermatocytes, spermatids and oocytes. Following gene targeting, matings of
      heterozygotes produce a normal Mendelian ratio with equal numbers of
      phenotypically normal males and females. However, males and females lacking Msy2
      are infertile. In Msy2-null males, spermatogenesis is disrupted in post-meiotic
      germ cells with many misshapen and multinucleated spermatids. No spermatozoa are
      found in the epididymis. The germ cell specificity and the critical functions
      played by this multifunctional DNA- and RNA-binding protein during
      spermatogenesis make Contrin, the human ortholog of MSY2, an attractive and novel
      target for male contraception.

PMID- 16413674
TI  - Glycan-modifying enzymes in luminal fluid of the mammalian epididymis: an
      overview of their potential role in sperm maturation.
AB  - Testicular spermatozoa and those present within the proximal regions of the
      epididymis are unable to bind to the zona pellucida, the extracellular coat that
      surrounds the oocyte, and fertilize the egg. They acquire progressive motility
      and fertilizing ability during passage through the epididymis. Mammalian
      spermatozoa undergo biochemical and physiological changes during epididymal
      transit that are collectively termed epididymal maturation. The process involves
      several intracellular and extracellular changes in the spermatozoon, including
      remodeling of the sperm plasma membrane and modifications of glycan moieties of
      the sperm surface glycoconjugates. Two sets of glycan-modifying enzymes, namely
      glycohydrolases that cleave sugar residues and glycosyltransferases that add
      sugar residues to the existing glycoconjugates, are present in the epididymal
      luminal fluid that surrounds spermatozoa. Thus, it is reasonable to expect that
      glycan chains present on the sperm surface will interact with these glycan
      modifying enzymes in the epididymal fluid. In this article, I have attempted to
      summarize and present an overview on the potential role of these glycan-modifying
      enzymes in sperm maturation.

PMID- 16413675
TI  - Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in
      multiple sclerosis.

PMID- 16413676
TI  - Proteasome inhibition induces both pro- and anti-cell death pathways in prostate
      cancer cells.
AB  - The proteasome-mediated protein degradation is critical for regulation of a
      variety of cellular processes, including cell cycle, cell death, differentiation
      and immune response. Proteasome inhibitors have recently been shown to be potent
      anti-cancer agents against a variety of cancer cells. Our study demonstrated that
      proteasome inhibitor MG132 (carbobenzoxy-L-leucyle-L-leucyl-L-leucinal) was a
      potent death-inducing agent for PC3 prostate cancer cells. MG132-induced cell
      death was partially inhibited by pan-caspase inhibitor zAVD-fmk and translational
      inhibitor cycloheximide. To understand the signaling pathways of proteasome
      inhibitor-induced cell death, we performed gene profiling study using Affymetrix
      human DNA microarrays to identify the genes whose expression was affected by
      proteasome inhibitor MG132 in PC3 cells. The genes with more than threefold
      increased expression induced by MG132 were functionally categorized into the
      following groups: heat shock and chaperone proteins, ubiquitination and protein
      degradation, transcription/translation factors, cell death and cell cycle arrest,
      signaling molecules and enzymes, and secreted cytokines. Among them, heat shock
      proteins and anti-oxidant enzymes may promote cell survival, while pro-death
      proteins such as GADD45B and STK17a may promote cell death. Interestingly,
      expression of a few autophagic genes was elevated by MG132 treatment.
      Furthermore, autophagy inhibitor 3-methyladenine partially inhibited MG132
      induced cell death, indicating that autophagic cell death may contribute to MG132
      induced cell death. Taken together, our results demonstrated that proteasome
      inhibition elicits activation of multiple signaling pathways in prostate cancer
      cells.

PMID- 16413678
TI  - Image acquisition with immersion objective lenses using electrons emitted with
      several tenths of an electron volt energies: towards high spatial resolution ESCA
      analysis.
AB  - This study aims to evaluate the spatial resolution achievable with photoelectrons
      in order to perform localised UPS or XPS analyses on various heterogeneous
      samples. This investigation is intentionally restricted to direct image
      acquisition by immersion objective lenses, involving electrons ejected with
      initial energies of several tenths of an electron-volt. In order to characterise
      the contribution of all optical elements, analytical investigations were
      associated to numerical simulations based on SIMION 7 software. The acquisition
      of high-quality images implies a simultaneous reduction in spherical and
      chromatic aberrations by a narrow aperture stop placed at the output pupil of the
      objective. With such limitations in useful emission angles, it is shown that
      monochromatic electron beams build images with a resolution of about 1 nm,
      especially for the acceleration bias mode where the focussing electrode is biased
      at a positive high voltage. Even energy dispersed electron beams, limited by a 4
      eV band pass spectrometer, can produce images convenient for highly localised
      ESCA analyses (resolution 3 nm), where the objective lens is associated with an
      aperture stop of 30 microm in diameter without using acceleration voltages above
      5000 V.

PMID- 16413677
TI  - Kinetics of thermolysis of some transition metal nitrate complexes with 1,6
      diaminohexane ligand.
AB  - Metal nitrate complexes of general formula [M(dah)(2)](NO(3))(2) (where M=Zn, Cu
      and Ni; dah=1,6-diaminohexane) have been prepared and characterized by elemental
      analysis, infrared spectroscopy (IR) and gravimetric method. The thermal
      decomposition has been studied using thermogravimetry (TG). Simultaneous
      thermogravimetry-differential thermogravimetry-differential thermal analysis (TG
      DTG-DTA) and differential scanning calorimetry (DSC) were done in N(2)
      atmosphere. Isothermal TG of initial decomposition of all these complexes, have
      been carried out to evaluate the kinetics of early thermolysis. Both, model
      fitting and isoconversional method have been used for the evaluation of the
      kinetics of thermal decomposition. Model fitting method have given the single
      value of activation energy (E) whereas, isoconversional method yields a series of
      E-value, which vary with extent of conversion. Ignition of the complexes was
      measured to see the response towards rapid heating with varying amounts. The
      thermal stability of the complexes was found to be in the order as
      [Zn(dah)(2)](NO(3))(2)>[Cu(dah)(2)](NO(3))(2) approximately
      [Ni(dah)(2)](NO(3))(2).

PMID- 16413680
TI  - N49 phospholipase A2, a unique subgroup of snake venom group II phospholipase A2.
AB  - A novel phospholipase A2 (PLA2) with Asn at its site 49 was purified from the
      snake venom of Protobothrops mucrosquamatus by using SP-Sephadex C25, Superdex
      75, Heparin-Sepharose (FF) and HPLC reverse-phage C18 chromatography and
      designated as TM-N49. It showed a molecular mass of 13.875 kDa on MALDI-TOF. TM
      N49 does not possess enzymatic, hemolytic and hemorrhagic activities. It fails to
      induce platelet aggregation by itself, and does not inhibit the platelet
      aggregation induced by ADP. However, it exhibits potent myotoxic activity causing
      inflammatory cell infiltration, severe myoedema, myonecrosis and myolysis in the
      gastrocnemius muscles of BALB/c mice. Phylogenetic analysis found that that TM
      N49 combined with two phospholipase A2s from Trimeresurus stejnegeri, TsR6 and
      CTs-R6 cluster into one group. Structural and functional analysis indicated that
      these phospholipase A2s are distinct from the other subgroups (D49 PLA2, S49 PLA2
      and K49 PLA2) and represent a unique subgroup of snake venom group II PLA2, named
      N49 PLA2 subgroup.

PMID- 16413679
TI  - Differential glycosylation of polyclonal IgG, IgG-Fc and IgG-Fab isolated from
      the sera of patients with ANCA-associated systemic vasculitis.
AB  - Post-translational modifications (PTMs) of proteins produced in vivo may be
      tissue, developmentally and/or disease specific. PTMs impact on the stability and
      function of proteins and offer a challenge to the commercial production of
      protein biotherapeutics. We have previously reported a marked deficit in
      galactosylation of oligosaccharides released from polyclonal IgG isolated from
      sera of patients with the anti-neutrophil cytoplasmic antibodies (ANCA)
      associated vasculitides; Wegener's granulomatosis (WG) and microscopic
      polyangiitis (MPA). Whilst normal polyclonal IgG molecules are glycosylated
      within the IgG-Fc region, approximately 20% of molecules also bear
      oligosaccharides attached to the variable regions of the light or heavy chain IgG
      Fab. It is of interest, therefore to compare profiles of oligosaccharides
      released from the IgG-Fc and IgG-Fab of normal IgG with that isolated from the
      sera of patients with WG or MPA. This study shows that whilst the
      oligosaccharides released from ANCA IgG-Fc are hypogalactosylated those released
      from IgG-Fab are galactosylated and sialylated. These results show that
      hypogalactosylation of IgG-Fc is not due to a defect in the glycosylation or
      processing machinery. It rather suggests a subtle change in IgG-Fc conformation
      that influences the addition of galactose. Remarkably, this influence is exerted
      on all plasma cells. Interestingly, a licensed monoclonal antibody therapeutic,
      produced in Sp2/0 cells, is also shown to be hypogalactosylated in its IgG-Fc but
      fully galactosylated in its IgG-Fab.

PMID- 16413681
TI  - Tesmilifene may enhance breast cancer chemotherapy by killing a clone of
      aggressive, multi-drug resistant cells through its action on the p-glycoprotein
      pump.
AB  - Tesmilifene is a novel potentiator of chemotherapy which, when added to
      doxorubicin, achieved an unexpected and very large survival advantage over
      doxorubicin alone in a randomized trial in advanced breast cancer. This trial was
      unusual in that the early endpoints (response rate and median progression-free
      survival) were equivalent in the two arms, despite the ultimate survival
      difference. These aspects, coupled with the absence of a coherent molecular
      mechanism of action, and a pending confirmatory trial, have led oncologists to
      hold judgement on this drug. This paper reacts to this in three ways: firstly, a
      forensic subgroup analysis is presented with an explanation as to why it strongly
      supports the veracity of the survival difference; secondly a novel cellular
      explanation is provided for the decoupling of the early and late (survival)
      endpoints; finally, a molecular mechanism of action is proposed, for the first
      time, which reconciles the peculiarities of the trial with the laboratory data
      and background literature. This hypothesis explains how tesmilifene could meld
      two of the apparent strengths of the cancer cell (drug resistance pumps, and
      hypoxia-adapted energetics) into a potent weapon of self-destruction. Tesmilifene
      is proposed to allow chemotherapy (e.g. anthracycline or taxane) to additionally
      kill a small but critical population (clone) of aggressive, multi-drug resistant
      cells, the benefits of which cannot be appreciated until a period of time (about
      6-8 months) has elapsed. These cells, present in women with more rapidly
      relapsing disease, very likely carry an energy-dependent extrusion pump which is
      paradoxically activated by tesmilifene plus the chemotherapy. The result is that,
      despite the chemotherapy's remaining extracellular, the cell dies from reactive
      oxygen species leaking from the electron chain transport in the abnormal
      mitochondria which characterize cancer. These mitochondria are activated in
      response to the ATP cost of this pump activation, in these predominantly
      glycolytic cells.

PMID- 16413682
TI  - Rebound phenomenon of inflammatory response may be a major mechanism responsible
      for increased cardiovascular events after abrupt cessation of statin therapy.
AB  - Inflammation has been recognized as having an important role in the development
      and progression of atherosclerosis. Statins reduce cardiovascular events mainly
      by cholesterol lowering. A large number of investigations have demonstrated that
      administration of statin could modify inflammatory response with a concurrent
      fall in cardiovascular events. Despite the known benefit of statin therapy, many
      cardiac patients abruptly discontinue therapy because of financial constraints,
      forgetfulness, or side effects. More recently, several studies have shown that
      abrupt cessation of statin therapy during treatment could increase the incidence
      of cardiac events in patients with atherosclerotic heart disease. However, the
      mechanisms of the increased incidence of cardiovascular events after abruptly
      stopping statin therapy are still unknown. A few data suggest that abrupt
      withdrawal of statin therapy deteriorates endothelial function, result in
      expression of pro-inflammatory gene involved in the development and progression
      of atherosclerosis. We hypothesis that rebound phenomenon of inflammatory
      response may be a major mechanism responsible for increased cardiovascular events
      after abrupt cessation of statin therapy. Our very recent data showed that abrupt
      termination of statin therapy resulted in a rapid increased C-reactive protein
      (CRP) and interleukin-6 (IL-6) levels in patients with hypercholesterolemia. This
      finding may be of important interest in the connection between inflammatory
      response and abrupt withdrawal of statin therapy in patients with coronary artery
      disease.

PMID- 16413683
TI  - Postulating that our neurological models for musculoskeletal support, movement,
      and emotional expression come from archetypal forms in early organisms.
AB  - The ability for humans, in principle, to almost effortlessly support themselves
      against gravity, to move with grace, and to express themselves in subtle and
      beautiful ways is amazing, given the number of moveable joints, variety of
      obstacles and intentions, and possible emotions to express. The actual mechanics
      are obviously astonishing but the models for these activities, in origin, must be
      simple. The basic hypotheses concerning these models are the following: The
      neurological model for the control of our musculoskeletal system is a simple
      support system from early organisms. This model involves a complementary
      relationship between the dorsal and ventral surfaces. There are three
      functionally distinct parts of the body, though not visually observable. These
      parts, named here "the director, motor, and rudder segments," are functionally
      distinct in optimal posture and movement. Healthy balance, posture, and movement
      result from their relatively independent yet coordinated actions. Forms of
      locomotion used by early organisms: peristalsis, lateral undulation, and dorsal
      ventral undulation are present in us yet. Four frozen phases of the dorsal
      ventral wave, for example, constitute four distinct postural and personality
      styles. I present these hypotheses together in this short paper as an
      introduction to a new illustration-dependent way to conceive some of our
      psychophysical realities. The hypotheses came from efforts to develop mental
      imagery to assist students in learning the Alexander technique (AT). In addition,
      a little known theory concerning four basic emotions and personality types,
      called the Fusion Theory, provided an initial concept of personality types. Four
      fixed postural patterns that I observed in teaching AT linked well to this
      personality typology. There is research that supports the use of mental imagery
      to affect change in body use, mostly in the sports and dance fields, but none
      exists addressing the specific imagery derived from these hypotheses. If these
      theories were confirmed, several areas could stand to benefit. Through imagery,
      some concepts involving musculoskeletal health could become more accessible to
      health-conscious and suffering individuals and give them a new way to become more
      connected to and responsible for their postural and mental health. Kinesiology,
      neurology, and psychology could develop a closer connection if research found
      that some aspects of posture, movement, and emotion all developed from allied
      origins. Specific benefits could come to the study of facial and body expression,
      understanding the physical basis of emotion and attitude, and understanding the
      experience of qualia in general.

PMID- 16413684
TI  - Gene-hypermutated isoforms of MYC protein: Tumour-suppressor P-53 protective
      initiation of apoptosis that normally prevents Burkitt's lymphoma tumorigenesis
      can be enhanced.

PMID- 16413686
TI  - PPARalpha activators may play role for the regression of ventricular hypertrophy
      in hypertensive and hyperlipidemic patients.

PMID- 16413685
TI  - Histopathological features of pretreatment neuroblastoma are of limited clinical
      significance following adjustment for clinical and biological marker status.
AB  - Neuroblastic tumours are morphologically classified into broad categories
      according to defined criteria, with further histopathological features described
      which may provide prognostic information, such as calcification, mitotic rate and
      the mitoses-karyorrhexis index; these may be combined with patient age and other
      factors to indicate high-risk and low-risk groups. However, recently, a range of
      biological molecular markers have proved to be of major prognostic importance in
      neuroblastic tumours, including MYCN amplification, 1p deletion, and 17q gain. It
      is therefore hypothesised that traditional histopathological features are now of
      limited clinical significance after adjustment for known clinical and biological
      pregnostic markers. Evidence to evaluate this hypothesis was obtained via a
      literature search to identify studies reporting on prognostic significance of
      histopathological features in multivariate analysis after adjustment for
      biological marker status. Thirteen studies were included of which four (1642
      subjects) reported an independent effect of histopathological findings, whereas
      nine (2385 subjects) reported no significant independent effect. All four studies
      examining both MYCN and other markers such as 1p, 11q or 17q status, reported no
      significant independent effect of histological parameters. Histopathological
      diagnosis remains the gold standard for the diagnosis and evaluation of
      paediatric tumours but in the evolving era of molecular evaluation of tumours,
      the role of traditional morphological assessments is likely to become
      increasingly obsolete, and diagnostic paediatric pathology departments must
      respond to the changing understanding of the biological basis of childhood
      malignancies towards routinely providing both diagnostic and molecular prognostic
      data from these small samples.

PMID- 16413687
TI  - The dental region constitutes a major blind spot in clinical medicine.
AB  - Headache, fatigue, and vertigo are collectively the commonest symptoms
      encountered in clinical medicine, yet in many cases their true aetiopathogenesis
      is unknown or unclear. It is postulated that an important reason why little
      significant progress is being made towards discovering the true aetiology of
      these symptoms is because physicians, almost universally, are failing to examine
      a large part of the head for common, readily observable intraosseous pathology
      which could conceivably cause these symptoms. The region not examined comprises
      the mandible, maxillae, and their appendages, and the intraosseous pathology not
      examined for includes impacted teeth, devitalized teeth, and residual infection,
      amongst others. The non-examination for pathology which could cause these
      symptoms has thus created a major blind spot in clinical medicine. It is
      conservatively estimated that more than 50 million people on the American and
      European continents may thereby be denied a proper clinical examination for the
      aetiology of these symptoms. Readily testable data, indicating the extent to
      which the medical profession as a whole has overlooked this pathology, is
      provided.

PMID- 16413689
TI  - Myopia as a latent phenotype of a pleiotropic gene positively selected for
      facilitating neurocognitive development, and the effects of environmental factors
      in its expression.
AB  - Myopia has become an almost pandemic problem in many populations. There are
      compelling evidence to suggest that myopia is a hereditary condition. However,
      myopia would constitute a definite selection disadvantage during most stages of
      human evolution, which is incompatible with its moderate to high prevalence in
      most modern populations. The rapid upsurge of myopia over just a few decades also
      implies that its inheritance does not follow any of the usual patterns, and
      environmental factors may have an important role in precipitating its occurrence
      in those who are genetically predisposed. Previous studies showed that myopes
      were, on average, more intelligent than non-myopes, and this association had been
      attributed to a biological link between eye growth and brain development. We
      propose a pleiotropic genetic model to explain the atypical epidemiologic and
      inheritance pattern of myopia and its relationship with neurocognitive
      development. This pleiotropic gene was positively selected for its facilitation
      of human intelligence. The myopic component is a latent phenotype; myopia will
      not be expressed unless some novel external factors are encountered (i.e. a
      "quirk" phenomenon). Therefore, the myopic component was selectively neutral in
      our ancestral environment. The net gain in Darwinian fitness enables the
      pleiotropic gene to attain a high frequency in the human population, as reflected
      by our current prevalence of myopia.

PMID- 16413688
TI  - Is it feasible to adjust bisphosphonate dose according to bone mineral density
      value in postmenopausal breast cancer patients with bone metastases?

PMID- 16413690
TI  - About a case of GIST occurring during pregnancy with immunohistochemical
      expression of epidermal growth factor receptor and progesterone receptor.
AB  - The coexistence of gastrointestinal stromal tumors (GISTs) and pregnancy is very
      rare. We are the first to add to the literature a case report of GIST occurring
      during pregnancy with immunohistochemical staining for epidermal growth factor
      receptor (EGFR) and progesterone receptor (PgR). A role of PgR and EGFR in tumor
      growth should not be excluded, and these findings indicate that the expression of
      these receptors could provide pertinent biological information required to
      determine adequate therapeutic regimens. In conclusion, considering that GIST
      occurring during pregnancy is a rare event, with frequent delay in diagnosis, it
      is important to consider this diagnosis for early recognition, correct diagnosis,
      and a better outcome.

PMID- 16413691
TI  - Histological analysis of lesions of the pineal region: a retrospective study of
      12 years.
AB  - Various types of tumors and non-tumor lesions arise in the pineal region. This
      study summarizes the experience the authors have gained with 54 lesions of the
      pineal region over the last 12 years. Histology was analyzed in all cases. Out of
      these 54 cases, four were non-tumor lesions. Of the 50 tumors, pineal parenchymal
      tumors (PPTs) were most common (42% (21/54)), followed by gliomas (40% (20/54)).
      The PPTs were pineoblastomas (10/21), PPT of intermediate differentiation (7/21),
      and pineocytomas (4/21). The other tumors included germ cell tumors (4/54),
      meningiomas (2/54), craniopharyngiomas (2/54), and choroid plexus papilloma
      (1/54). The non-tumor lesions were epidermoid cysts (2/54), tuberculous abscess
      (1/54), and cysticercosis (1/54). Immunohistochemically, all the PPTs showed
      cytoplasmic positivity for synaptophysin. Glial fibrillary acidic protein (GFAP)
      stained only the reactive astrocytes in these tumors except two cases of
      pineoblastoma, which showed GFAP positivity in some tumor cells, indicating glial
      differentiation. There are very few studies of pineal lesions, and there is no
      study from India in the indexed literature.

PMID- 16413692
TI  - Analysis of NKX3.1 expression in prostate cancer tissues and correlation with
      clinicopathologic features.
AB  - This study aimed to analyze NKX3.1 expression in tissue samples of benign
      prostate hyperplasia (BPH) and in three different prostate cancer categories. The
      correlation of NKX3.1 expression with clinical and pathologic features of
      patients having undergone radical prostatectomy also was investigated. NKX3.1
      expression was determined in tissue samples obtained from four different
      histopathological categories: (1) from patients treated with transurethral
      prostatectomy for BPH (n = 26), (2) localized prostate cancer patients subjected
      to radical prostatectomy (n = 38), (3) biopsy samples from prostate cancer
      patients who were metastatic at the initial admission (n = 10), and (4) tissue
      samples of prostate cancer patients administered antiandrogens, but who had
      undergone transurethral prostatectomy for infravesical obstruction (n = 11).
      Standard immunohistochemical staining was performed using an antiserum raised
      against recombinant human NKX3.1. Staining was seen in all categories of
      prostatic tissues. Immunohistochemistry staining scores were lower in prostate
      cancer patients. The staining scores were significantly higher in patients with
      BPH compared to metastatic or localized prostate cancer patients. Staining scores
      of patients with BPH and of those under antiandrogen therapy were similar. No
      significant correlation was found between NKX3.1 expression and tumor volume,
      Gleason sum scores, the presence of extraprostatic extension, tumor stage, or
      serum PSA. NKX3.1 expression is significantly decreased in prostate cancer
      patients when compared to BPH. However, the decline of NKX3.1 expression was not
      correlated with prostate cancer progression and was not associated with advanced
      stage. Thus, NKX3.1 expression is not a clinically valuable prognostic factor.

PMID- 16413694
TI  - Iatrogenic Kaposi's sarcoma following steroid therapy for nonspecific
      interstitial pneumonia with HHV-8 genotyping.
AB  - We present a case of iatrogenic Kaposi's sarcoma (KS) in a 64-year-old, human
      immunodeficiency virus (HIV)-negative woman with nonspecific interstitial
      pneumonia (NSIP) following steroid therapy. She suffered from longstanding
      exertional dyspnea, and was diagnosed to have NSIP by a thoracoscopic lung
      biopsy. After 4 months of steroid therapy, multiple purplish nodular or patchy
      skin lesions developed throughout the entire body. Microscopically, the skin
      lesions, consisting of closely packed spindle cells forming slit-like vascular
      structures, were diagnosed as typical KSs. The tumor cells were positive for
      CD34, factor VIII-related antigen, and human herpesvirus 8 (HHV-8)
      immunostainings. Using fresh tumor tissue and peripheral blood, polymerase chain
      reactions revealed the presence of HHV-8. Phylogenetic analysis of HHV-8 ORF K1
      genes disclosed that the strain belonged to the subtype II/C and had the M allele
      at the right-hand side of the genome. To the best of our knowledge, this case
      report is the first documentation of iatrogenic KS associated with NSIP. A brief
      review focusing on the HHV-8 genotypes of iatrogenic KS is also presented.

PMID- 16413693
TI  - Papillary glioneuronal tumor.
AB  - The descriptive term papillary glioneuronal tumor (PGNT) has been repeatedly
      applied to a morphologic subset of low-grade mixed glial-neuronal neoplasia of
      juvenile and young adult patients. We report on a 13-year-old boy with PGNT of
      the left temporal lobe, who presented with headaches and a single generalized
      seizure. On magnetic resonance imaging, tumor was seen as a large, moderately
      enhancing paraventricular mass with cyst-mural nodule configuration and slight
      midline shift. Perifocal edema was virtually absent. Gross total resection could
      be performed, followed by an uneventful recovery. Histologically, the tumor
      exhibited similar, if not identical, features as reported previously. These
      comprised a patterned biphasic mixture of sheets of synaptophysin-expressing
      small round cells and pseudorosettes of GFAP-positive rudimentary astrocytes
      along vascular cores. Focally, the latter imprinted a pseudopapillary aspect on
      this otherwise solid lesion. Both cellular components expressed non
      polysialylated neural cell adhesion molecule (NCAM)-L species, and several
      overlapping areas of synaptophysin and GFAP immunoreactivity were present. The
      mean MIB-1 labeling index remained below 1%. Signs of anaplasia, in particular
      mitotic figures, endothelial proliferation, or necrosis were consistently
      lacking. We perceive PGNT as a clinically and morphologically well-delineated
      subgroup of extraventricular neurocytic neoplasia, whose paradigmatic
      presentation may allow for consideration as an entity.

PMID- 16413695
TI  - Short-course radiotherapy is not optimal for spinal cord compression due to
      myeloma.
AB  - PURPOSE: To investigate the suitability of short-course radiotherapy (RT) for
      spinal cord compression (SCC) in myeloma patients. METHODS AND MATERIALS: Data
      for 172 myeloma patients irradiated between January 1994 and December 2004 for
      SCC were retrospectively evaluated. Short-course RT (1 x 8 Gy, 5 x 4 Gy, n = 61)
      and long-course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy, n = 111) were compared for
      functional outcome up to 24 months after RT. In addition, 10 potential prognostic
      factors were investigated. RESULTS: Improvement of motor function occurred in 90
      patients (52%). Forty-seven percent of nonambulatory patients regained the
      ability to walk. Functional outcome was significantly influenced by the time of
      developing motor deficits before RT. Improvement of motor function was more
      frequent after long-course RT than after short-course RT: 59% vs. 39% (p = 0.10)
      at 1 month, 67% vs. 43% (p = 0.043) at 6 months, 76% vs. 40% (p = 0.003) at 12
      months, 78% vs. 43% (p = 0.07) at 18 months, and 83% v 54% (p = 0.33) at 24
      months. A subgroup analysis of the long-course RT group demonstrated a similar
      functional outcome for 10 x 3 Gy when compared with 15 x 2.5 Gy and 20 x 2 Gy.
      CONCLUSIONS: Long-course RT is preferable for SCC in myeloma patients because it
      resulted in better functional outcome than short-course RT. Treatment with 10 x 3
      Gy can be considered appropriate.

PMID- 16413696
TI  - Rising prostate-specific antigen values during neoadjuvant androgen deprivation
      therapy: The importance of monitoring.
AB  - PURPOSE: To assess the impact of a rising prostate-specific antigen (PSA) level
      in patients receiving neoadjuvant androgen deprivation therapy (N-ADT) before
      external beam radiotherapy for prostate cancer. METHODS AND MATERIALS: From
      prospectively collected data, we identified 182 patients who received between 3
      and 12 months of N-ADT before definitive external beam radiotherapy and who had
      at least three PSA readings during the neoadjuvant period. One hundred fifty
      patients had PSA values that continued to fall (Non-Rise group), but 32 had a PSA
      value that started to rise (Rise group). The two groups were compared by Mann
      Whitney U and Pearson chi-square tests. Kaplan-Meier and log-rank analyses were
      performed for time to treatment failure, cause-specific survival (CSS), and
      overall survival (OS). RESULTS: The median follow-up was 62.5 months for the Non
      Rise group and 53 months for the Rise group. Patients who sustained a PSA rise
      during the N-ADT period had a shorter time to PSA relapse (p = 0.013), poorer CSS
      (p = 0.027), and poorer OS (p = 0.03). Multivariate analysis confirms the
      significance of a PSA rise during the N-ADT period for CSS (p = 0.035) and OS (p
      = 0.038). CONCLUSIONS: A subset of patients treated with N-ADT develop a rising
      PSA profile that likely represents early androgen resistance. They have
      significantly worse outcome.

PMID- 16413697
TI  - Intraoperative electron boost radiation followed by moderate doses of external
      beam radiotherapy in limb-sparing treatment of patients with extremity soft
      tissue sarcoma.
AB  - PURPOSE: To analyze long-term prognosis and morbidity after limb-sparing
      treatment of patients with extremity soft-tissue sarcoma, with intraoperative
      electron boost radiotherapy (IOERT) followed by a moderate dose of external beam
      radiotherapy (EBRT). METHODS AND MATERIALS: A total of 153 patients who were
      treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose
      was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation
      (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was
      assessed with Common Toxicity Criteria; late toxic effects were scored according
      to European Organization for Research and Treatment of Cancer/Radiation Therapy
      Oncology Group criteria. RESULTS: Five-year overall survival and 5-year local
      control rates were 77% and 78%, respectively. Whereas tumor size, patient age,
      and EBRT dose did not significantly affect outcome, resection status and grading
      were significant for survival; resection status and IOERT dose were significant
      for local control. Extremity salvage until death or time of follow-up was
      achieved in 90% of our patients, 86% of whom showed excellent limb function
      without impairment in activities of daily life. Acute toxicity Grade 2-4 was
      observed in 23% and late toxicity Grade 2-4 in 17% of patients. CONCLUSIONS:
      Treatment with IOERT combined with moderate doses of external beam irradiation
      yields high local control and extremity preservation rates in resected extremity
      soft-tissue sarcoma.

PMID- 16413698
TI  - The rapid uptake of concurrent chemotherapy for cervix cancer patients treated
      with curative radiation.
AB  - PURPOSE: In 1999, a series of clinical trials along with a clinical announcement
      from the National Cancer Institute (NCI) suggested that chemotherapy should be
      used concurrently with pelvic radiation in the management of cervical cancer. The
      purpose of this study is to examine the rate of chemotherapy use, in the province
      of Ontario, before and after these publications. METHODS: All incident cases of
      cervix cancer diagnosed between January 1, 1995, and March 31, 2001, were
      identified using the provincial cancer registry. These records were
      electronically linked to billing claims data and inpatient discharge abstract
      data. Patients receiving brachytherapy within 6 months of diagnosis were
      identified. The proportion receiving at least one injection of chemotherapy
      before brachytherapy was identified and compared in the "pre" and "post"
      publication group (April 1, 1999, cutoff). RESULTS: We identified 1039 cases as
      receiving curative radiation. In the pre cohort, 9.4% of patients received
      chemotherapy (95% CI, 7.3-11.4%) vs. 67.4% in the post cohort (95% CI, 61.8
      73.0%). The change occurred abruptly in the first quarter of 1999. CONCLUSION:
      There was a significant increase in chemotherapy use after the publication of the
      NCI alert and related trials. Reasons for rapid uptake are discussed.

PMID- 16413700
TI  - Stimulus-dependent processing of temporal order.
AB  - Two distinct conceptualisations of processing mechanisms have been proposed in
      the research on the perception of temporal order, one that assumes a central
      timing mechanism that is involved in the detection of temporal order independent
      of modality and stimulus type, another one assuming feature-specific mechanisms
      that are dependent on stimulus properties. In the present study, four different
      temporal-order judgement tasks were compared to test these two
      conceptualisations, that is, to determine whether common processes underlie
      temporal-order thresholds over different modalities and stimulus types or whether
      distinct processes are related to each task. Measurements varied regarding
      modality (visual and auditory) and stimulus properties (auditory modality: clicks
      and tones; visual modality: colour and position). Results indicate that the click
      and the tone paradigm, as well as the colour and position paradigm, correlate
      with each other. Besides these intra-modal relationships, cross-modal
      correlations show dependencies between the click, the colour and the position
      tasks. Both processing mechanisms seem to influence the detection of temporal
      order. While two different tones are integrated and processed by a more
      independent, possibly feature-specific mechanism, a more central, modality
      independent timing mechanism contributes to the click, colour and position
      condition.

PMID- 16413699
TI  - Radiotherapy in pediatric medulloblastoma: quality assessment of Pediatric
      Oncology Group Trial 9031.
AB  - PURPOSE: To evaluate the potential influence of radiotherapy quality on survival
      in high-risk pediatric medulloblastoma patients. METHODS AND MATERIALS: Trial
      9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of
      cisplatin and etoposide randomization of high-risk patients with medulloblastoma
      to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients
      were treated according to protocol guidelines and were eligible for the present
      analysis. Treatment volume (whole brain, spine, posterior fossa, and primary
      tumor bed) and dose prescription deviations were assessed for each patient. An
      analysis of first site of failure was undertaken. Event-free and overall survival
      rates were calculated. A log-rank test was used to determine the significance of
      potential survival differences between patients with and without major deviations
      in the radiotherapy procedure. RESULTS: Of 160 patients who were fully evaluable
      for all treatment quality parameters, 91 (57%) had 1 or more major deviations in
      their treatment schedule. Major deviations by treatment site were brain (26%),
      spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment
      volume or total dose deviations did not significantly influence overall and event
      free survival. CONCLUSIONS: Despite major treatment deviations in more than half
      of fully evaluable patients, underdosage or treatment volume misses were not
      associated with a worse event-free or overall survival.

PMID- 16413701
TI  - Time sharing in rats: A peak-interval procedure with gaps and distracters.
AB  - Four hypotheses (switch, instructional-ambiguity, memory decay, and time sharing)
      were evaluated in a reversed peak-interval procedure with gaps by presenting
      distracter stimuli during the uninterrupted timed signal. The switch,
      instructional-ambiguity, and memory-decay hypotheses predict that subjects should
      time through the distracter and delay responding during gaps. The time-sharing
      hypothesis assumes that the internal clock shares attentional and working-memory
      resources with other processes, so that both gaps and distracters delay timing by
      causing working memory to decay. We found that response functions were displaced
      both by gaps and by distracters. Computer simulations show that when combined,
      the memory-decay and time-sharing hypotheses can mechanistically address present
      data, suggesting that these two hypotheses may reflect different levels of
      analysis of the same phenomenon.

PMID- 16413702
TI  - Pharmaco-economics of community maintenance for opiate dependence: a review of
      evidence and methodology.
AB  - This literature review synthesizes and appraises evidence on the pharmaco
      economic value of community maintenance for opiate dependence. Included studies
      enrolled opiate-dependent subjects aged 18 years or over participating in a
      community maintenance programme. Cost-effectiveness/cost-utility analyses
      provided some evidence supporting the value of methadone maintenance in
      combination with psychosocial services and of heroin co-prescription. Evidence on
      the pharmaco-economic profile of maintenance with buprenorphine as compared with
      methadone is mixed. Few studies carried out an economic evaluation alongside a
      randomised controlled trial and studies adopting a modelling approach suffered
      from problems with the quality and validity of parameter estimates. Studies were
      also limited in the range of costs and consequences considered. The cost-benefit
      literature showed positive net benefits from community maintenance programmes. A
      longer length of stay of subjects in methadone maintenance was associated with
      greater reductions in criminal activity. However, measurement of benefits was
      limited to savings from reduced crime rates. Health benefits were rarely
      considered. Cost-benefit studies based on a before-and-after comparison were not
      able to consider the impact of treatment on mortality of opiate-dependent
      subjects. There is a need for better-designed economic evaluations that examine
      whether treatment benefits exceed costs, in terms of both financial benefits and
      health gain.

PMID- 16413703
TI  - Secreted antigens of Mycobacterium avium subspecies paratuberculosis as prominent
      immune targets.
AB  - We here describe the identification and characterization of three novel secreted
      Mycobacterium avium subsp. paratuberculosis antigens of 9, 15 and 34 kDa
      (Map2609, Map2942c and Map0210c, respectively) by screening a genomic expression
      library with a serum of a naturally infected clinical cow. The 9, 15 and 34 kDa
      antigens display strong homology to previously described M. tuberculosis
      antigens, TB8.4, MPT53 and Erp, respectively. Furthermore, these antigens were
      shown to be recognized by antibodies from infected cattle, when tested with a
      limited number of sera from subclinical (n=7) and clinical (n=3) infected cattle.

PMID- 16413704
TI  - Oral exposure to cadmium chloride triggers an acute inflammatory response in the
      intestines of mice, initiated by the over-expression of tissue macrophage
      inflammatory protein-2 mRNA.
AB  - Intestinal inflammation is an indispensable protective response of the gut immune
      system to aggressive injury from pathogens and/or chemicals. Although the major
      route of exposure to cadmium for most people is via food, causing the
      gastrointestinal tract to become the first target organ, very little information
      is available on whether cadmium exposure triggers the intestinal inflammatory
      response. We investigated in the present study the acute inflammatory response in
      the intestines of mice orally challenged with a single dose of cadmium chloride
      (CdCl(2)) by determining the gene expression of pro-inflammatory mediators with
      real-time PCR, and by examining the infiltration of inflammatory cells with a
      myeloperoxidase (MPO) assay and histological analysis of hematoxylin and eosin
      (H&E)-stained intestinal sections. The results show that CdCl(2) significantly
      increased the expression of macrophage inflammatory protein-2 mRNA (30-40 times
      the normal level) 3h and the activity of MPO (about 2 times the normal level) 24h
      after the challenge in the duodenal and proximal jejunal tissue. Furthermore,
      these increases were dose-dependent over a dosage range of 25-100mg/kg of body
      weight. The histological analysis confirmed that CdCl(2) induced mild to moderate
      villus damage and infiltration of inflammatory cells into the lamina propria. All
      these results demonstrate that oral exposure to CdCl(2) triggered an acute
      inflammatory response in the proximal intestine of mice, suggesting that the gut
      immune system was involved in the toxic effects of Cd on the gastrointestinal
      tract.

PMID- 16413706
TI  - Fracture reducing potential of hormone replacement therapy on a population level.
AB  - OBJECTIVES: To study the fracture reducing potential of hormone replacement
      therapy (HRT) at a population level, the effect of age on the fracture reducing
      potential of HRT, and to examine whether socio-economic factors confound the
      effects of HRT on fracture risk. SUBJECTS AND METHODS: Case-control study. All
      women who sustained any fracture during the year 2000 in Denmark served as cases
      (n=64,548). For each case, three age-matched controls were randomly drawn from
      the background population (n=193,641). The main exposure was the average daily
      dose of HRT (expressed as defined daily doses DDD/day). Adjustments were made for
      co-morbidity, socio-economic factors, and prior fracture. RESULTS: A fracture
      risk reduction was seen in women aged>or=50 years using >or=0.3 DDD/day. The risk
      reduction for any fracture was larger in women aged>or=60 years (0.3-0.99
      DDD/day: odds ratio (OR)=0.77, 95% confidence intervals (CI): 0.73-0.82, >or=1
      DDD/day: OR=0.61, 95% CI: 0.56-0.67) than in women aged 50-59 years (0.3-0.99
      DDD/day: OR=0.92, 95% CI: 0.85-0.99, >or=1 DDD/day: OR=0.77, 95% CI: 0.70-0.84).
      Larger risk reductions were seen for Colles' fractures (age 50-59 years: OR=0.64
      for 0.3-0.99 DDD/day, and OR=0.57 for >or=1 DDD/day, age>or=60 years: OR=0.52 for
      0.3-0.99 DDD/day, and OR=0.40 for >or=1 DDD/day). Adjustment only changed the
      estimates little. No difference between oral and dermal preparations could be
      found. CONCLUSIONS: Hormonal replacement therapy possesses a fracture-reducing
      potential at population level even at dosages lower than usually recommended. The
      risk reduction was larger with advancing age for any fracture and Colles'
      fractures.

PMID- 16413705
TI  - Identification of X- and Y-chromosome bearing buffalo (Bubalus bubalis) sperm.
AB  - The aim of this study was to identify the difference in DNA content
      characterizing the X- and Y-chromosome bearing sperm of buffalo. Sperm from six
      Murrah buffaloes and six Nili-Ravi buffaloes were collected and stained with
      Hoechst 33342 followed by flow cytometry analysis of the DNA content. Two
      symmetrical, separate but overlapping peaks presumed to be X- and Y-chromosome
      bearing sperm were detected. The difference in fluorescence intensity, which
      related to the DNA content, between the X- and Y-sperm was 3.59+/-0.11% for
      Murrah buffalo and 3.55+/-0.14% for Nili-Ravi buffalo, respectively. Significant
      differences were observed among males within each breed, but there were no
      differences between the averages of the two breeds. The results indicate that
      flow cytometric sorting of X- and Y-sperm of buffalo is feasible.

PMID- 16413707
TI  - Does tamoxifen therapy affect the hormone receptor expression and cell
      proliferation indices of endometrial polyps? An immunohistochemical comparison of
      endometrial polyps from postmenopausal women exposed and not exposed to
      tamoxifen.
AB  - OBJECTIVE: This study set out to test the null hypothesis that tamoxifen therapy
      would not affect the hormone receptor expression (oestrogen and progesterone
      receptors-ER and PR) or markers of cell proliferation/apoptosis (Ki67 and Bcl-2)
      of endometrial polyps from postmenopausal women exposed and not exposed to
      tamoxifen. METHODS: Endometrial polyps were prospectively obtained from women
      presenting with abnormal bleeding attending an out-patient hysteroscopy clinic
      who subsequently underwent endometrial polypectomy (16 from postmenopausal women
      not exposed to tamoxifen, 9 from women exposed to tamoxifen). Immunohistochemical
      staining for ER, PR, Ki67 and Bcl-2 was performed on polyps from both groups of
      women. Non-parametric statistical analysis was used (Mann-Whitney and Spearmans
      rank correlation). RESULTS: Endometrial polyps from tamoxifen users had
      significantly lower oestrogen receptor but increased progesterone receptor and
      Bcl-2 expression. There were no significant differences for proliferation markers
      (Ki67) between postmenopausal endometrial polyps exposed and not exposed to
      tamoxifen. CONCLUSIONS: Tamoxifen has a significant affect on hormone receptor
      expression and markers of apoptosis in endometrial polyps. The results support
      the hypothesis that tamoxifen promotes polyp growth by inhibiting apoptosis. The
      mechanism for this does not appear to be oestrogen receptor mediated.

PMID- 16413708
TI  - Sterile, injectable cyclodextrin nanoparticles: effects of gamma irradiation and
      autoclaving.
AB  - Sterility is required as stated by compendial requirements and registration
      authorities worldwide for an injectable drug carrier system. In this study,
      injectable nanospheres and nanocapsules prepared from amphiphilic beta
      cyclodextrin, beta-CDC6, were assessed for their in vitro properties such as
      particle size distribution, zeta potential, nanoparticle yield (%), drug
      entrapment efficiency and in vitro drug release profiles. Different sterilization
      techniques such as gamma irradiation and autoclaving were evaluated for their
      feasibility regarding the maintenance of the above mentioned nanoparticle
      properties after sterilization. It was found that amount these techniques,
      sterilization with gamma irradiation seemed to be the most appropriate technique
      with no effect on particle size, drug loading and drug release properties. Gamma
      irradiation causes some chemical changes on beta-CDC6 observed as changes in zeta
      potential but this does not lead to any significant changes for nanoparticle
      properties. Autoclaving caused massive aggregation for the nanoparticles followed
      by precipitation, which led to the conclusion that excessive heat disrupted
      nanoparticle integrity. Sterile filtration was not feasible since nanoparticle
      sizes were larger than the filter pore size and the yield after sterilization was
      very low. Thus, it can be concluded that blank and drug loaded beta-CDC6
      nanospheres and nanocapsules are capable of being sterilized by gamma
      irradiation.

PMID- 16413709
TI  - Enhancement of drug affinity for cell membranes by conjugation with lipoamino
      acids II. Experimental and computational evidence using biomembrane models.
AB  - Lipoamino acids (LAAs) are promoieties able to enhance the amphiphilicity of
      drugs, facilitating their interaction with cell membranes. Experimental and
      computational studies were carried out on two series of lipophilic amide
      conjugates between a model drug (tranylcypromine, TCP) and LAA or alkanoic acids
      containing a short, medium or long alkyl side chain (C-4 to C-16). The effects of
      these compounds were evaluated by monolayer surface tension analysis and
      differential scanning calorimetry using dimyristoylphosphatidylcholine monolayers
      and liposomes as biomembrane models. The experimental results were related to
      independent calculations to determine partition coefficient and blood-brain
      partitioning. The comparison of TCP-LAA conjugates with the related series of TCP
      alkanoyl amides confirmed that the ability to interact with the biomembrane
      models is not due to the mere increase of lipophilicity, but mainly to the
      amphipatic nature and the kind of LAA residue.

PMID- 16413710
TI  - Floating matrix dosage form for phenoporlamine hydrochloride based on gas forming
      agent: in vitro and in vivo evaluation in healthy volunteers.
AB  - Phenoporlamine hydrochloride is a novel compound that is used for the treatment
      of hypertension. The purpose of this study was to develop a sustained release
      tablet for phenoporlamine hydrochloride because of its short biological half
      life. Three floating matrix formulations of phenoporlamine hydrochloride based on
      gas forming agent were prepared. Hydroxypropyl methylcellulose K4M and Carbopol
      971P NF were used in formulating the hydrogel drug delivery system. Incorporation
      sodium bicarbonate into matrix resulted in the tablet floating over simulated
      gastric fluid for more than 6h. The dissolution profiles of all tablets showed
      non-Fickian diffusion in simulated gastric fluid. Moreover, release of the drug
      from these tablets was pH-dependent. In vivo evaluations of these formulations of
      phenoporlamine hydrochloride were conducted in six healthy male human volunteers
      to compare the sustained release tablets with immediate release tablets. Data
      obtained in these studies demonstrated that the floating matrix tablet containing
      more Carbopol was capable of sustained delivery of the drug for longer periods
      with increased bioavailability and the relative bioavailability of formulation
      (containing 25% Carbopol 971P NF, 8.3% HPMC K4M) showed the best bioequivalency
      to the reference tablet (the relative bioavailability was 1.11+/-0.19).

PMID- 16413711
TI  - Enhancement of the transdermal delivery of catechins by liposomes incorporating
      anionic surfactants and ethanol.
AB  - The aim of this study was to develop and evaluate liposomal formulations
      encapsulating tea catechins, which possess antioxidant and chemopreventive
      activities. Liposomes were characterized for size, zeta potential, and entrapment
      efficiency. Both in vitro and in vivo skin permeation were examined using nude
      mouse skin as a model. The results suggested that the liposomal composition plays
      an important role in affecting the efficiency of transdermal catechin delivery.
      Incorporation of anionic surfactants such as deoxycholic acid (DA) and dicetyl
      phosphate (DP) in the liposomes in the presence of 15% ethanol increased the (+)
      catechin permeation by five to seven-fold as compared to the control. The
      flexibility of bilayers is suggested as an important factor governing the
      enhancing effect of liposomes. Intercellular spaces within the stratum corneum
      but not shunt routes are the major pathways for catechin delivery from liposomes.
      (+)-Catechin and (-)-epicatechin are isomers which showed similar encapsulation
      efficiencies and skin permeation in liposomes. (-)-Epigallocatechin-3-gallate
      showed the highest encapsulation rate and in vivo skin deposition level in
      liposomes among all catechins tested. The stability and in vitro tranepidermal
      water loss test indicated the safety of the practical use of liposomes developed
      in this study.

PMID- 16413712
TI  - The expulsion of lipophilic drugs from the cores of solid lipid microspheres in
      diluted suspensions and in concentrates.
AB  - The aim of the study was to compare incorporation of bupivacaine base,
      bupivacaine stearate and indomethacin in diluted suspensions of lipospheres (10%,
      w/w of lipid) and in concentrates (50%, w/w of lipid). The lipid cores were
      composed of a mixture of solid and liquid triglycerides (Precirol and Miglyol
      4:1). The lipospheres sizing between 0.5-10 microm (suspensions) and 0.5-20
      microm (concentrates) were prepared using a hot emulsification with high-shear
      mixing and cold resolidification method. None of the studied drugs was
      successfully incorporated in the lipid core. The increased incorporation of drugs
      determined in the concentrated lipospheres was only apparent, since in fact all
      the dose was only attached to the surface of the lipid particles and was
      transferred to the aqueous phase in the course of an intensive agitation. The
      presence of hydrophilic polymers in the aqueous phase did not prevent the
      expulsion effect although drug precipitation was retarded. The expulsion effect
      did not correlate with the solubility of drugs determined in the bulk lipids.

PMID- 16413713
TI  - Preparation of immuno-stimulating complexes (ISCOMs) by ether injection.
AB  - This study investigated the application of the solvent dispersion technique,
      specifically ether injection, which has been successfully used in the preparation
      of liposomes, as a new, continuous and potentially scaleable method for the
      preparation of ISCOMs. Phosphatidylcholine (PC) and cholesterol (Chol) were
      dissolved in ether, which was injected into an aqueous solution, maintained at 55
      degrees C, containing Quil A. The influences of the following variables on ISCOM
      formation were investigated: ratio of PC:Quil A:Chol used, pumping rate, total
      lipid mass and concentration of buffer salts and Quil A in the aqueous phase. All
      samples were characterized by negative stain transmission electron microscopy,
      photon correlation spectroscopy and sucrose ultracentrifugation gradient. It was
      demonstrated that ISCOMs could be produced by this method but the homogeneity of
      the preparation was influenced by the conditions used. Homogeneous ISCOM
      preparations were consistently produced only when the weight ratio of PC:Quil
      A:Chol was 5:3:2 with a total lipid mass of 20 mg, the Quil A dissolved in a 0.01
      M phosphate buffer at a concentration of 6 mg in 4 ml, and the ether solution
      injected into the warmed buffer solution at a rate of 0.2 ml/min. Changing any of
      these variables resulted in more heterogeneous preparations in which ISCOMs
      typically co-existed with other colloidal structures such as worm-like and
      helical micelles, liposomes, lamellae and lipidic particles.

PMID- 16413714
TI  - Antiulcer and antimicrobial activity of Anogeissus latifolia.
AB  - Ethnobotanically, the bark of Anogeissus latifolia (Roxb. ex DC.) Wall. ex Guill.
      and Perr.(Combretaceae) has been reported to be used in the treatment of various
      disorders including stomach and skin diseases. We studied the antiulcer potential
      and antimicrobial activity of the 50% aqueous alcoholic extract in order to
      validate ethnobotanical claims regarding the plant use in the above-mentioned
      disorders. Gastroprotective potential of the Anogeissus latifolia extract (ALE)
      (100 and 200mg/kg/body weight) was studied on aspirin, cold-resistant stress
      (CRS), pylorus ligated (PL) and ethanol-induced ulcers. Status of the antioxidant
      enzymes superoxide dismutase (SOD) and catalase along with lipid peroxidation
      (LPO) was also studied in CRS-induced ulcers. The results of the present study
      showed for the first time that the ALE possessed gastroprotective activity as
      evidenced by its significant inhibition in the formation of ulcers induced by
      physical and chemical agents with a maximum of 84.16% curation (200mg/kg body
      weight) in CRS-induced ulcers. ALE decreased LPO and SOD with concomitant
      increase in catalase activity in CRS-induced ulcers. Moderate antibacterial
      activity and antifungal activity was also observed. High performance thin layer
      chromatography (HPTLC) showed the presence of gallic acid and ellagic acid
      (0.95%, w/w, 0.25%, w/w, respectively) in the plant. These findings could
      justify, at least partially, the inclusion of this plant in the management of
      gastric disorders in traditional medicine.

PMID- 16413715
TI  - Preliminary toxicity and phytochemical studies of the stem bark aqueous extract
      of Musanga cecropioides in rats.
AB  - These studies were designed to determine the preliminary oral toxicity profile of
      the crude aqueous stem bark extract of Musanga cecropioides (MCW) in adult
      Sprague-Dawley rats and its active chemical constituents by way of
      phytochemistry. The acute oral toxicity study was conducted using limit dose test
      of Up and Down Procedure according to the OECD/OCDE Test Guidelines on Acute Oral
      Toxicity (AOT425statPgm, version: 1.0) at a limit dose of 3,000 mg/kg body
      weight/oral route. Repeat dose oral toxicity studies were conducted by daily oral
      dosing of 750 mg/kg body weight of MCW dissolved in 1 ml of 0.9% saline and 1 ml
      of 0.9% saline to rats in the test and control groups, respectively, for 28 days.
      On day 29, blood samples for bioassays were collected by cardiac puncture under
      diethyl ether anesthesia. The phytochemical analysis was conducted using standard
      procedures. The LD(50) estimate of the extract was calculated to be greater than
      3,000 mg/kg body weight/oral route. The extract caused a significant (P<0.05)
      decrease in weight gain, differential eosinophil count and increase in serum
      creatinine but did not affect the organ weights, other serum electrolytes (Na(+),
      K(+), HCO(3)(-)), liver enzymes and other hematological indices in test rats. Its
      phytochemical analysis showed it contains saponins, flavonoids, alkaloids,
      tannins, phlobatannins, glycosides, reducing sugars and anthraquinones. These
      results show that the aqueous extract of Musanga cecropioides is relatively safe
      toxicologically when administered orally. Thus, its use in folkloric medicine as
      an oral antihypertensive is relatively safe when used over the tested period.

PMID- 16413716
TI  - Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on
      isolated rat hearts and conscious mice.
AB  - Cecropia pachystachya Mart. is popularly called "ambay" and extensively used in
      herbal medicine of South America for cough and asthma. In Argentina it grows in
      neotropical rainforest (Ntr C.p.) and in a temperate region (Tp C.p.). In a
      previous work we showed their hypotensive properties with different potency and
      toxicity, and now we studied the Tp C.p. effects in isolated heart from rats and
      central effects of both plants on the open-field test for mice. Tp C.p. produced
      a positive inotropic effect on isolated rat hearts, which was not affected by 1
      microM propranolol, suggesting that it is not due to a beta-adrenergic effect. In
      contrast, it was prevented by pretreatment with high [K](o) media, which
      stimulates the Na,K-ATPase pump, suggesting an inhibition of the pump by "ambay",
      as digital do. In the open-field test, both Ntr C.p. and Tp C.p. similarly
      decreased the spontaneous locomotion and exploratory behavior of mice at doses
      between 180 and 600 mg/kg. Ntr C.p. potentiated the effect of 3 mg/kg diazepam to
      one similar to 10 mg/kg diazepam, but was not antagonized by 0.5 mg/kg
      flumazenil. Amphetamine at 5 mg/kg prevented the sedative effect of Ntr C.p.
      Chromatographic analysis showed that both plants have a qualitatively similar
      fingerprint but quantitatively differed in at least three components. Although
      the purpose was not to identify them, both plants have at least 10 compounds. Two
      of them were in higher amount in Tp C.p. than in Ntr C.p., and then, they could
      be responsible for the cardiovascular toxicity of Tp C.p. In conclusion, the
      results suggest that ambay has cardiotonic and sedative properties. The sedative
      effect could be useful in cough treatment. The extract resulted additive to
      benzodiazepines but it did not bind to the same site on GABA-A receptor, and it
      was interfered by the dopamine release produced with amphetamine.

PMID- 16413717
TI  - Antimicrobial activity of the methanolic extract from the stem bark of
      Tridesmostemon omphalocarpoides (Sapotaceae).
AB  - The methanolic extract and fractions from the stem bark of Tridesmostemon
      omphalocarpoides were investigated for their in vitro antimicrobial properties as
      well as their phytochemical constituents. The stem bark was collected from
      Yaounde, in the Centre Province of Cameroon. The antimicrobial activity of the
      extract and fractions against two Candida species and seven aerobic bacteria was
      evaluated on the basis of the inhibition zones (IZ) using agar hole diffusion
      method, the minimal inhibition concentration (MIC) and the minimal microbicidal
      concentration (MMC) by the macrodilution method. The results indicated
      significant anticandidal and antibacterial effect of the methanolic extract and
      fractions against all the nine microorganisms tested. Preliminary phytochemical
      analysis of methanolic extract showed the presence of biologically active
      components namely alkaloids, steroids, tannins, saponins, phenols, polyphenols
      and flavonoids. The acute toxicity of the methanolic extract was also studied.
      This was found to be non-toxic to the inbred Wistar rats treated per os. The
      results of this study suggested that the stem bark of this plant could be safely
      used in the treatment of some infectious diseases.

PMID- 16413718
TI  - The hydroalcoholic extract of Salvia elegans induces anxiolytic- and
      antidepressant-like effects in rats.
AB  - Behavioral effects of a hydroalcoholic (60% ethanol) extract from the leaves of
      Salvia elegans Vahl (Lamiaceae) were studied in male Sprague-Dawley rats. The
      extract was administered intraperitoneally and its effects on spontaneous motor
      activity (total motility, locomotion, rearing and grooming behavior) were
      monitored. Putative anxiolytic and antidepressant properties of Salvia elegans
      were studied in the elevated plus-maze test (EPM) and in the forced swimming test
      (FST), respectively. Deleterious effects of Salvia elegans on learning and memory
      were also studied by using active and passive avoidance paradigms. The results
      revealed that all doses (3.12, 12.5, 25 and 50 mg/kg) of the extract caused a
      significant decrease in total motility, locomotion, rearing and grooming
      behavior. Only the dose of 12.5 mg/kg increased the exploration of the EPM open
      arms in a similar way to that of diazepam (1 mg/kg). In the FST, all doses of the
      extract induced a reduction of immobility, in a similar way to that of fluoxetine
      (10 mg/kg) and imipramine (12.5 mg/kg), along with a significant increase in the
      time spent in swimming behavior. Acquisition of active avoidance responses was
      disrupted by pre-treatment with the extract, but retention of a passive avoidance
      response was not significantly modified. These results suggest that some of the
      components of the hydroalcoholic extract of Salvia elegans have psychotropic
      properties, which deserve further investigation.

PMID- 16413719
TI  - Development of a simulation system for performing in situ surface tests to assess
      the potential severity of head impacts from alleged childhood short falls.
AB  - There is considerable debate in the medical literature surrounding the issue of
      fatal child head injuries being caused by short falls. When reviewing a case
      history a medical expert will form an opinion of the likely cause of an injury
      based on his/her knowledge of the literature, training and experience of similar
      cases. The severity of an injury is determined by the age of the victim, fall
      height, body impact site and the impact surface. A medical expert, when forming
      an opinion, is invariably assisted by a description of the scene or scene
      photographs and assumes the mechanical response of the floor conforms in the same
      way to "similar" surfaces. The impact response characteristics of the entire
      surface mixture is critically important when considering the potential for head
      injury to a child due to a short fall. However, at present during an
      investigation, the response of a surface to a head impact remains an unknown,
      since a simple description of, or cursory glance at, a floor surface is
      insufficient in determining its potential to cause injury. This paper documents
      the development of a simulation system for assessing the impact response, and
      potential to cause injury, of domestic floor surfaces during short falls. The
      method utilises a headform and drop tower adapted from techniques and current
      standards used to assess the potential for childhood head injuries of playground
      surfaces and pedestrian-bonnet impacts. The results suggest that the potential of
      a surface to cause head injury is dependent on the entire surface mixture,
      including the top surface layer (e.g. carpet and underlay), the underlying
      surface (wood, chipboard or concrete) and the support material (joists, supports.
      etc.). The results illustrate a wide range of injury potential between surface
      mixtures. The simulation system shows the potential to discriminate between
      differences in surface mixture. In conclusion, the authors suggest that in future
      investigations, the response of the entire surface mixture be taken into account
      when forming an opinion on the injury potential of short falls.

PMID- 16413720
TI  - A case of congenital neuromuscular disease with uniform type 1 fibers.
AB  - Congenital neuromuscular disease with uniform type 1 fibers is a rare form of
      congenital nonprogressive myopathy. We report a 3-year-old boy with this disease
      who showed delayed motor developmental milestones and recurrent acute respiratory
      failure. He obtained head control at 16 months, crawled at 17 months and sat
      alone at 20 months, but still could not walk at age 44 months. His mental
      development was good; he could speak 3-word sentences at 44 months. Scoliosis,
      bilateral congenital dislocation of the hips, bilateral undescended testes and
      hemangioma simplex on the right lower limb were also seen. Muscle biopsy at the
      age of 8 months showed more than 99% of the myofibers were type 1. This is the
      first case of congenital neuromuscular disease with uniform type 1 fibers
      accompanied by recurrent acute respiratory failure. This case may be clinically
      more severe than previously reported cases.

PMID- 16413721
TI  - Reflex periodic spasms induced by eating.
AB  - We report on two patients with reflex periodic spasms (PS) triggered by eating.
      Both patients also had significant cognitive and motor deficits. In both
      patients, reflex eating PS started during meal and occurred repeatedly at
      intervals of about 5-30 s, and the whole episode lasted about 10-15 min with 15
      20 consecutive PS. Clinically, each PS was characterized by the trunk and head
      flexion, eyeball elevation, abduction of the upper limbs, and loss of
      consciousness. Ictal EEG recordings of PS revealed high-voltage sharp slow waves
      followed by a brief 1-2s voltage attenuation. Simultaneous EMG recording of right
      and left deltoid muscles revealed an abrupt increase of tone lasting 0.5-1.5s. In
      two patients, the origins of reflex PS were perirolandic suprasylvian and
      temporolimbic, respectively, because the first patient had focal epilepsy
      associated with cortical malformation including bilateral opercular dysplasia and
      the second one had cryptogenic temporal lobe epilepsy.

PMID- 16413722
TI  - [Management of lower respiratory tract infections in immunocompetent adults
      (community-acquired pneumonia and acute exacerbation of chronic obstructive
      pulmonary disease): the challenge of a new consensus conference].

PMID- 16413723
TI  - The effects of alcohol on immunity and bacterial infection in the lung.
AB  - When faced with invading pathogens that can lead to infection, patients must
      mount an effective and appropriate immune response. Altered immune function in
      patients who abuse alcohol has long been described in the medical literature. The
      alcohol-consuming host is particularly prone to infections in the lung, including
      bacterial pneumonia and tuberculosis. Over the last several decades, there has
      been increased interest in the immune mechanisms that underlie the increased risk
      of infection observed in this population. This article will review the basic
      immunology involved in the host response to an infection and then describe how
      alcohol disrupts many of these immune mechanisms. It will further provide an
      overview of lung infections which have been linked to alcohol abuse, and finally,
      it will address the evolving therapeutic approaches of the immune system that are
      being advanced to assist in caring for immunosuppressed hosts.

PMID- 16413724
TI  - Severe impairment of ventricular compliance accounts for advanced age-associated
      hemodynamic dysfunction in rats.
AB  - Advanced aging is associated with hemodynamic dysfunction in rats as in humans.
      The aim of this study was to assess the mechanisms of development of left
      ventricular (LV) dysfunction in the rat model of aging. In vivo hemodynamics and
      ex vivo LV papillary muscle mechanics, myofilaments sensitivity to calcium in
      skinned fibers and pressure/volume curves in isolated perfused hearts were
      performed in 3, 24 and 28 month old (mo) male Wistar rats. Hemodynamic
      dysfunction occurs in 28 mo rats and is characterized by both a systolic and
      diastolic dysfunction and a LV hypertrophy (+34.7% of LV weight). In papillary
      muscle, normalized active developed force and myofilament sensitivity to calcium
      were unchanged between 24 and 28 months of age. In contrast, both resting
      force/total force ratio in papillary muscle and the slope of the pressure/volume
      curves in isolated heart are increased between 3 and 24 mo but also between 24
      and 28 mo, indicating a progression of the impairment of both papillary muscle
      stiffness and LV compliance in advanced aging. Hemodynamic dysfunction occurring
      at advanced age, i.e. 28 mo in rats mainly results from impairment of ventricular
      compliance resulting from fibrosis.

PMID- 16413725
TI  - Helical CT in the diagnosis of acute lower gastrointestinal haemorrhage.
AB  - INTRODUCTION: A pilot study to evaluate helical computer tomography (CT) as a
      diagnostic tool for acute lower gastrointestinal tract (GIT) bleeding. CT was
      compared to conventional angiography (CA) and colonoscopy for the diagnosis and
      detection of bleeding site in suspected cases of acute lower GIT bleeding.
      METHODS: Seven patients presenting with acute lower GIT bleeding, between June
      and November 2002, underwent CT examinations. All of these seven patients
      underwent CA following CT. Emergency colonoscopies were performed on five
      patients investigated with both CT and CA. Median delay from the most recent
      episode of hematochezia to CT was two and a half hours, to CA was 3h, and to
      colonoscopy was 4h. None of the patients underwent nuclear medicine (NM) bleeding
      studies. RESULTS: Haemoglobin drop in all patients was greater than 15 g/L in the
      first 24h of presentation. The mean age was 68.86 years (range, 49-83 years).
      Comparing CT and CA, there were four concordant and three discordant results.
      Both modalities had concordant findings of two active bleeding sites, one non
      bleeding rectal tumour, and one negative case result. In three patients, the
      source of bleeding was found on CT whereas CA was negative. Emergency
      colonoscopies performed in all of these three patients confirmed blood in the
      colon/ileum. CONCLUSION: Early experience suggests that CT is a safe, convenient
      and accurate diagnostic tool for acute lower GIT haemorrhage. It raises questions
      regarding the sensitivity of CA. A new management algorithm for acute lower GIT
      haemorrhage using CT as the pre-CA screening tool is being proposed based on the
      preliminary findings. Positive CT will allow directed therapeutic angiography,
      while negative CT will triage patients into alternative management pathways.

PMID- 16413726
TI  - Imaging of infectious spinal disorders in children and adults.
AB  - The aim of this review article is to outline the imaging of infectious disorders
      of the spine in adults and children. The clinical presentation, potential routes
      of infection and the pathogens commonly identified are discussed. The value of
      different imaging modalities in the diagnosis of spinal infection is presented
      including radiographic, CT, MR imaging and Nuclear Medicine including PET. The
      use of image guided techniques for diagnosis and subsequent treatment is briefly
      covered. The major differential diagnoses of infectious disorders of the spine
      are identified and contrasted with the typical findings in infection. The use of
      follow up imaging is evaluated.

PMID- 16413727
TI  - Flow injection determination of adenine at trace level based on luminol-K2Cr2O7
      chemiluminescence in a micellar medium.
AB  - A novel flow injection chemiluminescence (CL) analysis method for the
      determination of adenine in the presence of sodium dodecylbenzene sulfonate
      (SDBS) surfactant micelles is described. This method is based on the luminescent
      properties of the luminol-K2Cr2O7-adenine in alkaline medium sensitized by SDBS.
      The optimized experimental conditions were evaluated and the possible mechanism
      was discussed by examining CL emission spectrum and the effect of various free
      radical scavengers on CL emission intensity. The CL increase is linearly related
      to the concentration of adenine in the range of 2.92x10(-6) to 4.38x10(-10) mol l
      1 with a detection limit of 2.46x10(-10) mol l-1 (S/N=3). The relative standard
      deviation for 2.92x10(-7) mol l-1 samples was 1.67% (n=12). The proposed method
      has been applied to the determination of adenine in human serum.

PMID- 16413728
TI  - Simultaneous determination of captopril and hydrochlorothiazide in human plasma
      by reverse-phase HPLC from linear gradient elution.
AB  - A simple, rapid and sensitive high-performance liquid chromatographic method for
      the simultaneous determination of captopril and hydrochlorothiazide in human
      plasma samples was developed. Captopril was derivatized with 2,4'
      dibromoacetophenone (pBPB) to form a captopril-pBPB adduct. From acidified serum
      plasma samples, the hydrochlorothiazide and derivatized captopril was extracted
      with 5 ml ether, then with 5 ml dichloromethane. Effective chromatographic
      separation was achieved using a C(18) column (DIAMONSIL 150 mmx4 mm i.d., 5
      microm) based on an acetonitrile-trifluoroacetic acid-water gradient elution at a
      flow rate of 1.2 ml/min. The internal standard (IS), derivatized captopril and
      hydrochlorothiazide were detected at 263 nm and were eluted at 4.2, 6.8 and 16.9
      min, respectively. No endogenous substances were found to interfere. The limit of
      quantification for hydrochlorothiazide and derivatized captopril in plasma were
      3.3 and 7 ng/ml. The calibration curve for derivatized captopril showed linearity
      in the range 20-4000 ng/ml, with a regression coefficient corresponding to 0.9993
      and the coefficient of the variation of the points of the calibration curve being
      lower than 10%. The calibration curve for hydrochlorothiazide showed linearity in
      the range 10-1200 ng/ml, with a regression coefficient corresponding to 0.9999
      and the coefficient of the variation of the points of the calibration curve being
      lower than 10%. The method was suitably validated and successfully applied to the
      determination of captopril and hydrochlorothiazide in human plasma samples.

PMID- 16413729
TI  - Recent trends in the determination of polyphenols by electromigration methods.
AB  - An overview mapping recent trends in the determination of polyphenols of natural
      origin (mostly flavonoids) and their synthetic derivatives by electromigration
      methods is presented. The overview (covering the period of the recent 5 years and
      comprising 61 references) is focused on capillary zone electrophoresis (CZE) and
      micellar electrokinetic chromatography (MEKC) with various detection methods.
      Techniques comprising on-line pre-separation such as isotachophoresis (ITP)-CZE
      and flow-injection-CZE, chiral separations and CZE evaluation of antioxidation
      activity are also discussed.

PMID- 16413730
TI  - Determination of paracetamol in pure and pharmaceutical dosage forms by pulse
      perturbation technique.
AB  - A new procedure for kinetic determination of paracetamol in pharmaceuticals is
      proposed. The method is based on potentiometric monitoring of the concentration
      perturbations of the matrix reaction system being in a stable non-equilibrium
      stationary state close to the bifurcation point. In the case considered as the
      matrix system, the Bray-Liebhafsky oscillatory reaction is used. The response of
      the matrix system to the perturbations by different concentrations of paracetamol
      is followed by a Pt-electrode. Proposed method relies on the linear relationship
      between maximal potential shift, DeltaEm, and the logarithm of added paracetamol
      amounts. It is obtained in optimized experimental conditions for variable amounts
      of paracetamol in the range 0.0085 and 1.5 micromol. The sensitivity and
      precision of proposed method were quite good (0.0027 micromol as the limit of
      detection and 2.4% as R.S.D.). Some aspects of possible chemical interactions
      between paracetamol and matrix are discussed. Applicability of the proposed
      method to the direct determination of paracetamol in pharmaceutical formulations
      was demonstrated.

PMID- 16413731
TI  - A new lignan from the Jian-er syrup and its content determination by RP-HPLC.
AB  - The Jian-er syrup is a commonly used traditional Chinese medicinal preparation
      refined from two herbs, Metaplexis japonica (Thunb.) Makino and Justicia
      procumbens L. A new lignan, named 6'-hydroxy-Justicidin B, was isolated from the
      ethyl acetate extract of the Jian-er syrup and its structure was established on
      the basis of spectral analysis. The content of 6'-hydroxy-Justicidin B in the
      Jian-er syrup was determined by RP-HPLC for the first time. Chromatographic
      separation was achieved on an Agilent Zorbax SB-C18 column (150 mmx4.6 mm i.d., 5
      microm) at 25 degrees C and the mobile phase was a mixture of acetonitrile and
      water (31:69 v/v) detected at 256 nm at a flow rate of 1.0 ml/min. This method
      was validated in terms of selectivity, linearity, precision, accuracy, limit of
      detection, limit of quantitation and solution stability. It can be used to
      control the quality of this preparation effectively.

PMID- 16413732
TI  - Optimization and validation of a dissolution test for famotidine tablets using
      flow injection analysis.
AB  - A dissolution test for famotidine tablets was optimized and validated using flow
      injection analysis (FIA). The effect of dissolution parameters such as pH, medium
      and stirring speed was studied, while the ruggedness of the procedure was
      validated. All measurements were performed using a simple direct
      spectrophotometric flow injection assay (lambdamax=265 nm) that has also been
      optimized and fully validated in terms of linearity, limit of detection,
      precision, selectivity and accuracy. Linearity was obeyed in the range 50-150% of
      famotidine (20-60 mg L-1), while the detection limit (0.1 mg L-1) and
      repeatability (sr<1.0%, n=12) were satisfactory. The sampling rate was 30 h-1.
      The dissolution results during quality and stability control of two batches of
      famotidine tablets obtained by the flow injection method were in good agreement
      with high-performance liquid chromatography (HPLC).

PMID- 16413733
TI  - Determination of the antimalaria drug artemether in pharmaceutical preparations
      by differential pulse polarography.
AB  - A differential pulse polarographic method has been developed for the
      determination of artemether in its pharmaceutical formulations. The polarographic
      behaviour of artemether was examined in various buffer systems over the pH range
      3.0-10.0. In phosphate buffer pH 5.5/methanol solution (7:3, v/v) the
      differential pulse polarograms displayed reproducible peaks at Ep-0.01 V versus
      Ag/AgCl. Under these conditions strict linearity between artemether concentration
      and peak height was observed in 3.4x10(-7)-3.0x10(-5)mol/L concentration range
      (R=0.9998). The detection limit was calculated to be 32 ng/mL. The polarographic
      method was applied to the determination of the content of artemether in tablets
      and capsules by using the standard addition method. The analysis of tablets
      containing 20mg artemether showed a mean value of 19.73 mg with a relative
      standard deviation (R.S.D.) of +/-1.01%. A content of 39.74 mg artemether was
      found in 40 mg capsules with a relative standard deviation of +/-0.53%. The
      polarographic method is characterised to be cheap, precise and not time-consuming
      and can therefore be used for routine analysis of artemether in its
      pharmaceutical preparations.

PMID- 16413734
TI  - Binding studies of taxanes to human serum albumin by bioaffinity chromatography
      and circular dichroism.
AB  - The binding to human serum albumin (HSA) of the antitumoural drug paclitaxel and
      of several structural analogues has been characterized by bioaffinity
      chromatography and circular dichroism. A ranking of the taxanes was obtained for
      their affinity to the protein by measuring their retention times on an albumin
      chromatographic column. This also allowed the calculation of the drug bound
      percentage. Affinity resulted significantly affected by the nature of the
      isoserinic side chain, the presence of the 1,14-carbonate moiety and the
      substituent at C-7, showing that the hydrophobicity of the drug is fundamental in
      the binding process. The analysis demonstrated that the organic solvent highly
      alters the interaction mechanism of taxanes to the protein and so the affinity
      results. Circular dichroism experiments supported this hypothesis. Furthermore,
      taxanes binding to the serum carrier was characterized by displacement
      chromatography, by adding into the mobile phase selected competitors, (S)
      ibuprofen and valproic acid, that are known to bind to specific binding sites on
      HSA. These experiments established a non-cooperative binding mechanism.

PMID- 16413735
TI  - Determination of cefmetazole residue at pharmaceutical manufacturing facilities
      by chemiluminescence flow injection analysis.
AB  - Application of a sensitive and rapid flow injection analysis (FIA) method with
      luminol chemiluminescence detection for determination of trace amounts of
      cefmetazole (CMZ) in cephamycin antibiotic residue in pharmaceutical
      manufacturing facilities and on pharmaceutical manufacturing equipment has been
      investigated. The method was shown to be sensitive at a level of limit of
      detection of 0.06 ng/ml and for linear concentrations in the range of 0.3-1.5
      ng/ml. Average recoveries of CMZ from stainless steel plates and glass plates
      were 62.1% and 60.1%, respectively, by adding 15 ng/100 cm2, and that of air
      sampling filters was 91.9% by adding 3 ng/filter. The proposed method has been
      successfully applied to the determination of CMZ residue in samples collected
      from an actual manufacturing facility and equipment. According to the results, no
      detectable CMZ residue was observed, therefore it was verified that no
      contamination had occurred to other pharmaceutical products manufactured in the
      facility.

PMID- 16413736
TI  - Capillary electrophoresis method development for determination of impurities in
      sodium cysteamine phosphate samples.
AB  - A capillary electrophoresis method for determination of impurities in sodium
      cysteamine phosphate-an alternative drug to use in place of cysteamine
      (Cystagon), Mylan Laboratories Inc.) in the treatment of cystinosis-was
      developed. The administration of cysteamine, divided in four doses due to the
      short half-life of this drug, is a helpful treatment, but several patients show
      intolerance, due to the very unpleasant odor and taste of cysteamine. Sodium
      cysteamine phosphate is less organoleptic aversive and also has a larger active
      time, allowing the compression of the doses to 2 per day, increasing the
      acceptance of the drug. In the developed method the two main decomposition
      products of sodium cysteamine phosphate, cystamine and cysteamine, can be
      determined with LOQs of 30 microg/ml (0.2%) and 16 microg/ml (0.1%),
      respectively. The background electrolyte is 15 mM ammonium acetate (pH 8.85) with
      10% methanol and the separation takes less than 4 min. UV detection is performed
      at 195 nm. This volatile method was developed with the purpose of further
      hyphenation to a mass spectrometer.

PMID- 16413737
TI  - Quantitative determination of puerarin in dog plasma by HPLC and study on the
      relative bioavailability of sustained release tablets.
AB  - To evaluate the bioavailability of puerarin sustained release tablet (SR-Tab.)
      and Yufengningxin tablet (YU-Tab.), a liquid chromatography method was developed
      and validated to determine puerarin in dog plasma. Chromatographic separation was
      performed on Diamonsil C18 column using a mixture of methanol-acetic acid-water
      (25:6:69, v/v/v) delivered at a flow rate of 1.0 ml/min and detected by UV. 4
      Hydroxybenzaldehyde was used as the internal standard. The linear range for
      puerarin was from 60 to 1800 ng/ml (r=0.9991) with a limit of quantitation of 60
      ng/ml. Within-day accuracy and precision ranged from -3.0 to 2.2% and from 1.2 to
      4.3%, between-day accuracy and precision ranged from -4.1 to 2.6% and from 1.3 to
      5.7%, respectively. The mean extraction recoveries of puerarin determined over
      the three concentrations were (90.3+/-5.2)%, (95.7+/-1.4)% and (93.1+/-3.5)%. A
      significant difference was observed in main pharmacokinetic parameters of Tmax,
      Cmax and AUC0-infinity between puerarin SR-Tab. and YU-Tab. in dogs. The smoother
      plasma concentrations were obtained from SR-Tab. in dogs and the results were as
      expected.

PMID- 16413738
TI  - Photoinduced chemiluminescence of pharmaceuticals.
AB  - A screening test for the forward development of chemiluminescence systems able to
      determine pharmaceutical compounds is reported. The test is based on the on-line
      photodegradation of the drugs by using a photoreactor consisting of 697 cmx0.5 mm
      PTFE tubing helically coiled around an 8 W low-pressure mercury lamp.
      Photodegraded pharmaceuticals are detected by direct chemiluminescence of the
      resulting photofragments and their subsequent reaction with potassium
      permanganate in sulphuric acid medium as oxidant. The screening comprised 97
      compounds with different molecular structures and relevant members of the most
      important families of pharmaceuticals are tested (amino acids, carboxylic acids,
      nitrocompounds, phenyl-alkyl and aromatic amines, sulphonic acid amides,
      polycarbocyclics, monocyclic N-containing heterocyclics, bicyclic N-containing
      heterocyclics, tricyclic N-containing heterocyclics, N-S containing
      heterocyclics...). Due to the relevant influence of the medium for the
      photodegradation a wide range of pH's and buffer solutions were studied. The
      proposed strategy (photoinduced chemiluminescence, Ph-CL) allows the development
      of systems for the determination of many pharmaceuticals which do not present
      "native" chemiluminescence (e.g. chloramphenicol, dextromethorpham, riboflavin,
      ephedrine, piperazinamide, chlotrimazole, theophylline...). Moreover, Ph-CL
      allows to increase the sensitivity of chemiluminescence procedures based on
      direct chemiluminescence detection (e.g. sulphonamides, thiazides, nicontinamide,
      nortryptiline, levamisole, phenylbarbituric acid...).

PMID- 16413739
TI  - Determination of phillyrin in rat plasma by high-performance liquid
      chromatography and its application to pharmacokinetic studies.
AB  - A simple high-performance liquid chromatographic method was developed to study
      the pharmacokinetics of phillyrin in rat after intravenous administration. Plasma
      was extracted with ethyl acetate after addition of the internal standard,
      arctiin. Separation was achieved on a reversed-phase C18 column with UV detection
      at 228 nm. The calibration curves were linear ranging from 0.052 to 26.670
      microg/ml. The intra- and inter-day precisions were no more than 9.83% and
      12.31%, respectively. The average recovery of phillyrin was 95.44% from plasma.
      And the limit of quantification (LOQ) was estimated as 0.026 microg/ml with an
      intra-day relative standard deviation (R.S.D.)<or=20%. The analytical sensitivity
      and accuracy of this assay were adequate for characterization of phillyrin in rat
      plasma and the assay has been applied successfully to the in vivo kinetic study
      of phillyrin in rats.

PMID- 16413740
TI  - Study of the interaction of an anticancer drug with human and bovine serum
      albumin: spectroscopic approach.
AB  - The interactions between gemcitabine hydrochloride (GEM) and bovine serum albumin
      (BSA) or human serum albumin (HSA) have been studied by spectroscopic techniques.
      By the analysis of fluorescence spectrum and fluorescence intensity, it was
      observed that the GEM has a strong ability to quench the intrinsic fluorescence
      of both BSA and HSA through a static quenching procedure. The association
      constants of GEM with BSA and HSA were determined at different temperatures based
      on fluorescence quenching results. The negative DeltaH degrees and positive
      DeltaS degrees values in case of GEM-BSA and GEM-HSA complexes showed that both
      hydrogen bonds and hydrophobic interactions play a role in the binding of GEM to
      BSA or HSA. Experimental results showed that the binding of GEM to BSA or HSA
      induced conformational changes in BSA and HSA. From the quantitative analysis
      data of CD spectra, the alpha-helix of 57.58% and 34.82% in free BSA and free HSA
      decreased to 40.82% and 29.84% in BSA-GEM and HSA-GEM complexes, respectively,
      and hence confirmed that the secondary structure of protein was altered by GEM.
      The interactions of BSA and HSA with GEM were also confirmed by UV absorption
      spectra. The distance, r, between donor (BSA or HSA) and acceptor (GEM) was
      obtained according to the Forster's theory of non-radiation energy transfer. The
      effects of common ions on the binding constants of both BSA-GEM and HSA-GEM
      complexes were also investigated.

PMID- 16413741
TI  - Diverse biomodulatory effects of glucomannan from Candida utilis.
AB  - Using four experimental model systems, it was demonstrated that glucomannan (GM)
      isolated from the cell wall of the industrial yeast Candida utilis revealed a
      broad range of protective activities. This effect depended on the nature and mode
      of action of the counteracting genotoxic compound as well as on the experimental
      model system used. In the Saccharomyces bioprotectivity assay, GM increased
      resistance towards ofloxacin-induced toxicity in the wild type and recombination
      repair-deficient yeast strains significantly enhancing survival of the cells. In
      the chromosomal aberration assay, GM exerted anticlastogenic effect against
      maleic hydrazide induced clastogenicity in Vicia faba L. In the DNA-topology
      assay, GM protected plasmid DNA from the breaks induced by Fe(2+) ions, but
      enhanced damage induced by bleomycin and hydrogen peroxide. In the cell
      revitalization assay, it enhanced cytotoxic/cytostatic effect of teniposide
      applied to mouse leukemia cells. Thus, depending on the experimental model, GM
      acted as antimutagen, anticlastogen, DNA breaks inhibitor or inducer, and as
      cytotoxic/cytostatic effect enhancer. Several possible mechanisms of
      bioprotective action underlying the observed activities are suggested including
      iron chelation and free radical scavenging. The results imply that GM is a
      polysaccharide with marked biological activities and suggest its potential
      biomedical application, especially in combination with other bioactive compounds.

PMID- 16413742
TI  - Transcription of human neuronal nitric oxide synthase mRNAs derived from
      different first exons is partly controlled by exon 1-specific promoter sequences.
AB  - The human neuronal nitric oxide synthase (NOS1) gene is subject to extensive
      splicing. A total of 12 NOS1 mRNA species have been identified. They differ in
      their 5' ends and are derived from 12 different first exons (termed exons 1a to
      1l). Various cell lines whose NOS1 first exon expression patterns were
      representative of human brain, skin, and skeletal muscle were identified. These
      included A673 neuroepithelioma cells, SK-N-MC neuroblastoma cells, HaCaT
      keratinocyte-like cells, and C2C12 myocyte-like cells. In these cell lines,
      correlations were found between the exon 1 variants preferentially expressed and
      the promoter activities of their cognate 5' flanking sequences. These data
      demonstrate that expression of the different exon 1-related splice variants of
      NOS1 mRNA is controlled directly (at least in part) by the associated 5' flanking
      sequences.

PMID- 16413744
TI  - Pediatric laryngotracheal stenosis and airway reconstruction: a review of voice
      outcomes, assessment, and treatment issues.
AB  - Laryngotracheal stenosis is defined as a congenital or acquired narrowing of the
      airway. Congenital causes may include subglottic membranous or cartilaginous
      narrowing. Acquired causes may include trauma due to prolonged endotracheal or
      tracheal intubation or laryngotracheal injury. Although advances have been made
      over the past 30 years in reconstructive surgeries to improve airway patency in
      these patients, long-term laryngeal function for voice production is not well
      defined in this population. This review examines causes, symptoms and signs, and
      methods for diagnosing laryngotracheal stenosis. Surgical management procedures
      are briefly summarized. The current literature on voice outcomes is summarized.
      The predominant voice characteristics in the population are presented, although
      results are challenged by the heterogeneity of voice presentation and paucity of
      data from instrumental measures. Considerations for subjective and instrumental
      assessment, measures of quality of life, instrumental methods, and treatment
      options specific to the needs of this population are discussed. Research
      strategies to identify long-term outcomes of surgical and behavioral treatments
      in this population are posed.

PMID- 16413743
TI  - Gestational exposure to methylmercury and n-3 fatty acids: effects on high- and
      low-rate operant behavior in adulthood.
AB  - Fish in the diet is the major source of methylmercury (MeHg) exposure, but eating
      fish also provides important nutrients. Many fish species contain essential long
      chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), an
      omega-3 (or n-3) fatty acid, that is important for neural development and
      function. To examine interactions between MeHg and n-3 fatty acids, female Long
      Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm MeHg via drinking water,
      approximating exposures of 0, 40, and 400 mug/kg/day. They also received pre- and
      postnatal exposure to a diet containing either fish oil or coconut oil, creating
      a 2 (Diet)x3 (MeHg) full factorial design, with 6-8 rats per cell. The diets were
      high or marginal, respectively, in n-3 fatty acids but approximately equal in n-6
      fatty acids. No exposure-related effects on developmental milestones or growth
      were noted. Behavior was evaluated using a series of rapidly increasing fixed
      ratio (FR) schedules of sucrose reinforcement; 1, 5, 25 and 75 lever presses were
      required for sucrose delivery, with three sessions provided at each requirement.
      This phase was followed by four sessions of a differential-reinforcement-of-low
      rate-behavior (DRL) schedule, in which presses preceded by 10 s (or more) without
      a press were reinforced. Subsequently, several progressive ratio (PR) schedules
      that increased response requirements throughout a single session by a rate of 5%,
      10%, or 20% were imposed. Rats exposed during gestation to MeHg had significantly
      higher response rates than controls under the large FR schedules, during the
      first session of DRL, and the PR 5% schedule, but neither fish oil nor coconut
      oil modified MeHg's effects. This finding is consistent with hypotheses that
      developmental MeHg exposure produced perseverative responding or altered the
      sensitivity of behavior to its reinforcing consequences and that certain
      reinforcement contingencies can unmask MeHg's effects.

PMID- 16413745
TI  - Jaw opening in novice and experienced classically trained singers.
AB  - This study examined the amount of jaw opening used by two groups of singers,
      those with less than 4 years of training (novice) and those with more than 8
      years of training (experienced) in the Western tradition of opera and art song.
      Movement of the jaw in the superior-inferior plane was measured with the use of a
      lightweight head-mounted cephalostat with a strain gauge. The subjects spoke and
      then sung a carrier phrase "I say b(v)p," where (v) was each of three vowels,
      [a], [i], and [u]. The phrase was first spoken with a natural inflection and then
      sung on a repeated pitch at three notes from the low, medium, and high singing
      voice range. There was no statistically significant difference in jaw opening
      between the two groups of singers. Vowel was significant for jaw opening in both
      groups, with [a] being produced with more jaw opening than [i] or [u]. The
      voicing condition was also significant for jaw opening with greater jaw opening
      being used as pitch increased. In general the amount of jaw opening was smallest
      for the low singing voice condition and greatest for the high singing voice
      condition. The jaw opening most typically was less in the low voice condition
      than in the speech condition and then increased for both the medium and high
      voice tasks. All but two singers used more jaw opening on the [a] vowel than the
      other two vowels at all voicing conditions.

PMID- 16413746
TI  - Segmentation in virtual colonoscopy using a geometric deformable model.
AB  - The Geometric Deformable Model is developed for accurate colon lumen segmentation
      as part of an automatic Virtual Colonoscopy system. The deformable model refines
      the lumen surface found by an automatic seed location and thresholding procedure.
      The challenges to applying the deformable model are described, showing the
      definition of the stopping function as the key to accurate segmentation. The
      limitations of current stopping criteria are examined and a new definition,
      tailored to the task of colon segmentation, is given. First, a multiscale edge
      operator is used to locate high confidence boundaries. These boundaries are then
      integrated into the stopping function using a distance transform. The hypothesis
      is that the new stopping function results in a more accurate representation of
      the lumen surface compared to previous monotonic functions of the gradient
      magnitude. This hypothesis is tested using observer ratings of colon surface
      fidelity at 100,000 randomly selected locations in each of four datasets. The
      results show that the surfaces determined by the modified deformable model better
      represent the lumen surface overall.

PMID- 16413747
TI  - Betaglycan induces TGF-beta signaling in a ligand-independent manner, through
      activation of the p38 pathway.
AB  - Betaglycan, a cell surface heparan sulphate proteoglycan, is traditionally
      thought to function by binding transforming growth factor type beta (TGF-beta)
      via its core protein and then transferring the growth factor to its signaling
      receptor, the type II receptor. However, there is increasing evidence that the
      function of betaglycan is more complex. Here, we have evaluated the role of
      betaglycan through adenoviral expression (Adv-BG) in myoblasts and fibroblasts
      and found that in Adv-BG-infected cells, the activity of p3TP-Lux and pCTGF-Luc
      reporter after transient transfection, as well as fibronectin synthesis, all of
      which are target processes for TGF-beta, were highly increased in the absence of
      TGF-beta. It is known that this cytokine strongly inhibits myogenin induction in
      myoblasts. In Adv-BG-infected myoblasts, the activity of pMyo-Luc reporter after
      transient transfection was strongly inhibited in the absence of TGF-beta. These
      effects were not precluded by applying TGF-beta-blocking antibodies, the soluble
      TGF-beta type II receptor, or soluble betaglycan to sequester TGF-beta present in
      the cell medium. Furthermore, the data suggest that the cytoplasmic domain of
      betaglycan is required for this TGF-beta-independent response, giving further
      support to a ligand-independent signaling effect for betaglycan. The process also
      seemed independent of Smad-2 phosphorylation, although Adv-BG infection induced
      p38 phosphorylation, and SB239063, an inhibitor of the p38 pathway, inhibited
      p3TP-Lux-driven activity. These results suggest a novel signaling mechanism for
      betaglycan, which is independent of the canonical TGF-beta signal pathway
      although it involves TGF-beta receptors and takes place through p38 pathways.

PMID- 16413749
TI  - Efficiency of apples, strawberries, and tomatoes for reduction of oxidative
      stress in pigs as a model for humans.
AB  - OBJECTIVE: The present study investigated the potency of apples, strawberries,
      and tomatoes in decreasing oxidative stress in pigs as a model for humans.
      METHODS: Forty-eight growing pigs were individually penned in metabolic cages and
      divided into six groups. All groups received isocaloric daily rations composed of
      a basal diet supplemented with starch, linseed oil, linseed oil and apples,
      linseed oil and strawberries, linseed oil and tomatoes, or linseed oil, apples,
      strawberries and tomatoes. Oxidative stress was evaluated at the beginning and at
      the end of the 22-d experimental period by measuring the degree of DNA damage in
      mononuclear blood cells, the concentration of malondialdehyde (MDA) in plasma,
      the MDA excretion rate, the concentration of tocopherols in plasma, plasma total
      antioxidant status, and erythrocyte glutathione peroxidase concentration.
      RESULTS: The results confirmed that the linseed oil diet significantly increased
      MDA formation in the body and DNA damage to mononuclear blood cells in comparison
      with the starch diet. Although the MDA concentration in plasma was significantly
      decreased in all fruit groups, urine MDA excretion rate was decreased only in the
      linseed oil/apple and linseed oil/apple/strawberry/tomato groups. Supplementation
      with fruit significantly decreased DNA damage, was more pronounced in the linseed
      oil/apple and linseed oil/apple/strawberry/tomato groups. Significantly lower
      glutathione peroxidase concentrations were observed only in the linseed
      oil/strawberry group. CONCLUSIONS: Our findings support the hypothesis that
      supplementation with apples, strawberries, or tomatoes effectively decreases
      oxidative stress by decreasing MDA formation in the body and by protecting
      mononuclear blood cells against increased DNA damage. This effect was
      particularly pronounced in the group supplemented with a fruit mixture; among the
      single fruit supplements, the most beneficial effect was obtained with apples.

PMID- 16413748
TI  - Lipopolysaccharide-induced transcriptional activation of interleukin-10 is
      mediated by MAPK- and NF-kappaB-induced CCAAT/enhancer-binding protein delta in
      mouse macrophages.
AB  - We have previously revealed that LPS can activate transcription of the IL-10 gene
      promoter through transcription factors Sp1, C/EBPbeta and C/EBPdelta in mouse
      macrophages. In this study, we determined that NF-kappaB and MAPK signal
      pathways, including ERK, JNK, and p38, were all involved in LPS-induced IL-10
      gene expression. Treatment of cells with the pharmacological inhibitors of ERK,
      JNK, p38 and NF-kappaB respectively inhibited LPS-induced IL-10 protein
      expression in a dose-dependent manner. These inhibitors also decreased the LPS
      induced IL-10 mRNA expression at a high concentration used. With transient
      overexpression of the IkappaB expression plasmids, or the dominant negative
      plasmids of ERK2, JNK, p38 together with reporter vector containing IL-10
      promoter region, all four expression plasmids inhibited LPS-induced IL-10
      promoter activity individually. It is known that the increase in protein and DNA
      binding of C/EBPbeta and delta could activate IL-10 gene expression. In this
      study, we also identified that all four pharmacological inhibitors inhibited the
      protein expression of C/EBPdelta individually, but not C/EBPbeta. In the presence
      of all three MAPK inhibitors, or only NF-kappaB inhibitor, LPS-induced protein
      expression and DNA binding of C/EBPdelta were completely inhibited
      simultaneously, and LPS-induced expression of IL-10 protein and mRNA was also
      inhibited totally. Taken together, these results suggested that LPS-induced IL-10
      expression was mediated at least through the pathway of NF-kappaB- and MAPK
      induced protein expression and DNA binding of C/EBPdelta.

PMID- 16413750
TI  - Predictive factors of survival in patients with peritoneal carcinomatosis on home
      parenteral nutrition.
AB  - OBJECTIVE: We worked to identify predictors of survival in patients with
      carcinomatosis on home parenteral nutrition (HPN). METHODS: Survival rate was
      evaluated in 152 terminal patients (45 men and 107 women) with peritoneal
      carcinosis on HPN. Selected anthropometric measurements (weight and body mass
      index), laboratory tests (serum albumin, cholesterol, cholinesterase [CHE],
      hemoglobin, and lymphocyte count) and clinical variables (ascites, pain, and
      vomiting) were recorded at baseline. A Karnofsky Performance Status (KPS) was
      also determined. RESULTS: Sites of primary cancer were the stomach in 31.6%,
      ovaries in 27.6%, colorectum in 19.7%, and other in 21.1%. At baseline patients
      had abnormally low values: 55.3% had a body mass index no greater than 20.0
      kg/m2, 40.4% had a serum albumin level lower than 3.0 g/dL, 55.7% had a
      lymphocyte count no higher than 1200/mm3, 54.6% had a cholesterol level lower
      than 160 mg/dL, and 63.1% had a CHE level lower than 5400 U/L. Pain, ascites,
      vomiting, and a KPS score no higher than 40 were observed in 44.1%, 55.3%, 76.3%,
      and 51.3% of patients, respectively. Survival ranged from 6 to 1269 d (median 45
      d). Patients with a KPS score no higher than 40 had shorter survival than did
      patients with a KPS score of at least 50 (median 28.5 versus 81, P = 0.0001).
      Multivariate analysis (R2 = 0.152 for the entire model) indicated that KPS (P =
      0.01) and CHE (P = 0.034) were significant predictors of survival. Moreover,
      three different combinations of selected clinical and laboratory variables
      identified patients who survived fewer than 60 d (high specificity). CONCLUSIONS:
      Time of survival widely varied among terminal cancer patients; identification of
      predictive factors could help to draw up guidelines to improve indications for
      HPN. In this study, traditional predictors (KPS, albumin, pain, and vomiting) and
      CHE level appeared to be a useful survival predictor index in incurable patients
      with peritoneal carcinosis on HPN.

PMID- 16413751
TI  - Role of partially hydrolyzed guar gum in the treatment of irritable bowel
      syndrome.
AB  - Irritable bowel syndrome (IBS) is the world's most common gastrointestinal
      functional disorder and is associated with several social and economic costs.
      Health-related quality of life is often impaired in patients with IBS. The
      pathophysiologic mechanisms underlying IBS remain poorly defined. The therapeutic
      approach to patients with IBS is based on symptoms, and fibers may play an
      important role in treatment. Among the various types of fiber, water-soluble, non
      gelling fibers seem to be a promising option for treatment of IBS. Partially
      hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling fiber that has
      provided therapeutic benefits. In clinical trials, PHGG decreased symptoms in
      constipation-predominant and diarrhea-predominant forms of IBS and decreased
      abdominal pain. Further, an improvement in quality of life was observed in
      patients with IBS during and after treatment with PHGG. Moreover, PHGG seems to
      have prebiotic properties because it increases the colonic contents of short
      chain fatty acids, Lactobacilli, and Bifidobacteria.

PMID- 16413752
TI  - Oral creatine supplementation in humans does not elevate urinary excretion of the
      carcinogen N-nitrososarcosine.
AB  - OBJECTIVE: Creatine is a popular oral supplement in athletes and may have
      therapeutical potential in neuromuscular diseases. It has been hypothesized that
      creatine ingestion can lead to increased formation of the carcinogen N
      nitrososarcosine. METHODS: We investigated in a double-blind, placebo-controlled
      study the urinary excretion of N-nitrososarcosine after 1-wk high-dose (20 g/d)
      and 20-wk low-dose (5 g/d) creatine supplementation in healthy humans. RESULTS
      AND CONCLUSION: Creatine ingestion does not systematically increase urinary N
      nitrososarcosine excretion.

PMID- 16413753
TI  - Effects of olive oil and tomato lycopene combination on serum lycopene, lipid
      profile, and lipid oxidation.
AB  - OBJECTIVE: We compared the effect of two diets (a diet high in olive oil and a
      diet high in carbohydrate and low in olive oil) with high lycopene content and
      other controlled carotenoids on serum lycopene, lipids, and in vitro oxidation.
      METHODS: This was a randomized crossover dietary intervention study carried out
      in Launceston, Tasmania, Australia in healthy free-living individuals. Twenty-one
      healthy subjects who were 22 to 70 y old were recruited by advertisements in
      newspapers and a university newsletter. A randomized dietary intervention was
      done with two diets of 10 d each. One diet was high in olive oil and the other
      was high in carbohydrate and low in olive oil; the two diets contained the same
      basic foods and a controlled carotenoid content high in lycopene. RESULTS:
      Significant increases (P<0.001) in serum lycopene concentration on both diets
      were to similar final concentrations. Higher serum high-density lipoprotein
      cholesterol (P<0.01), lower ratio of total cholesterol to high-density
      lipoprotein (P<0.01), and lower triacylglycerols (P<0.05) occurred after the
      olive oil diet compared with the high-carbohydrate, low-fat diet. There was no
      difference in total antioxidant status and susceptibility of serum lipids to
      oxidation. CONCLUSIONS: Serum lycopene level changes with dietary lycopene intake
      irrespective of the amount of fat intake. However, a diet high in olive oil and
      rich in lycopene may decrease the risk of coronary heart disease by improving the
      serum lipid profile compared with a high-carbohydrate, low-fat, lycopene-rich
      diet.

PMID- 16413754
TI  - Effect of zinc on biochemical parameters and changes in related gene expression
      assessed by cDNA microarrays in pituitary of growing rats.
AB  - OBJECTIVE: The present study simultaneously investigated the effects of different
      zinc (Zn) levels on the growth performance and relative biochemical parameters in
      growing rats and analyzed the molecular mechanism of zinc influencing food
      intake. METHODS: Three diets with different Zn levels--Zn adequate (ZA; 35.94
      mg/kg, control), Zn deficient (ZD; 3.15 mg/kg), and Zn overdose (ZO; 347.50
      mg/kg)--were fed to rats for 6 wk. Dietary Zn was supplemented with ZnSO4. The
      relation between zinc and food intake was studied by pituitary cDNA microarrays.
      RESULTS: Compared with ZA group, rats fed the ZD diet showed decreases in body
      weight (P < 0.01), food intake (P < 0.05), tissue zinc concentrations (P < 0.01),
      and specific activities of alkaline phosphatase (P < 0.01) and copper/Zn
      superoxide dismutase (P < 0.05), whereas the ZO diet had positive effects on body
      weight (P < 0.05), zinc concentrations (P < 0.01), and alkaline phosphatase
      activity (P < 0.05). The villi of the jejunum became shorter (P < 0.01),
      shriveled, and flattened. This change in morphology decreased absorption surface
      area, and there was a substantial decrease (P < 0.01) in villi number per unit
      area in ZD rats. Metallothionein concentration was increased in livers of rats
      fed ZD (P < 0.01) and ZO (P < 0.05) diets. Moreover, ZD and ZO influenced normal
      growth and development of organs. The results from pituitary cDNA arrays
      indicated that different Zn levels affect gene expression of appetite-related
      peptides, including neuropeptide-Y, melanin-concentrating hormone, ghrelin,
      calcitonin gene-related product, and serotonin. CONCLUSION: The present results
      showed that zinc deficiency has a negative effect on the growth performance and
      biochemical parameters of rats. The ZO diet increased body weight (P < 0.05) but
      had no effect (P > 0.05) on food intake, copper/Zn superoxide dismutase activity,
      and intestinal morphology. The ZD diet decreased rat food intake by regulating
      appetite-related gene expression in the pituitary gland.

PMID- 16413756
TI  - Drug absorption in the elderly: biopharmaceutical considerations for the
      antiepileptic drugs.
AB  - The management of antiepileptic drug (AED) pharmacokinetics remains a challenge
      in the treatment of patients with epilepsy. Drug characteristics, such as protein
      binding, mechanisms of drug elimination, and the potential for
      pharmacokinetic/pharmacodynamic interactions, are important considerations for
      drug selection and may help determine overall effectiveness. In elderly patients
      with epilepsy, the likelihood of polytherapy, along with physiological changes
      associated with aging, can make pharmacokinetic issues even more significant. One
      aspect of pharmacokinetics that has received less attention is the process of
      oral drug absorption. Aging can have variable effects on the gastrointestinal
      system. Some of these physiological changes have the potential to impact
      absorption patterns of some medications, including AEDs. Altered oral protective
      reflexes, xerostomia, and delayed esophageal emptying in elderly patients may
      complicate oral administration of some medications. Altered gastric pH could
      modify drug absorption, and modified gastric emptying rates can influence the
      bioavailability of some AEDs. Finally, intestinal transit times may be slower in
      elderly patients compared to younger patients, possibly altering the absorption
      of some AEDs. These age-related physiological changes that may affect AED
      pharmacokinetics should be considered when treating elderly patients with
      epilepsy.

PMID- 16413755
TI  - Dysgnathia, orthognathic surgery and spinal posture.
AB  - The aim of this study was to evaluate the spine by video rasterstereography
      before and after orthognathic surgery. Twenty-nine patients (17 patients with a
      skeletal class III, 7 patients with a skeletal class II, and 5 patients with
      mandibular asymmetry) were evaluated preoperatively and 1 year postoperatively.
      Video rasterstereography is a method of back surface measurement and shape
      analysis using the moire topography. Orthognathic surgery in cases of class III
      and asymmetry did not lead to significant changes in body posture. In class II
      patients it led to some changes in body posture, but without orthopaedic
      consequences. It is concluded that orthognathic surgery causes minimal or no
      change in body posture.

PMID- 16413757
TI  - Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based
      morphometric study.
AB  - Previous studies have provided evidence supporting a neuroplastic effect of
      atypical antipsychotics. The present investigation explores the short-term
      effects of risperidone on brain parenchyma by performing voxel-based morphometry
      on baseline and 6-week follow-up MRI scans obtained from 15 neuroleptic-naive
      individuals with first-episode psychosis treated with risperidone and 15 healthy
      controls. The risperidone-treated subjects demonstrated changes in grey matter
      and white matter in several brain regions, including superior temporal gyrus. No
      areas of change were found in controls. The results of this exploratory
      investigation support the possibility that risperidone has short-term effects on
      brain parenchyma in individuals with first-episode psychosis.

PMID- 16413758
TI  - Disruption of orofacial movement topographies in congenic mutants with dopamine
      D5 but not D4 receptor or DARPP-32 transduction 'knockout'.
AB  - The role of D(1)-like [D(1), D(5)] and D(2)-like [D(2), D(3), D(4)] dopamine
      receptors and dopamine transduction via DARPP-32 in topographies of orofacial
      movement was assessed in restrained mice with congenic D(4) vs. D(5) receptor vs.
      DARPP-32 'knockout'. D(4) and DARPP-32 mutants evidenced no material phenotype;
      also, there were no alterations in topographical responsivity to either the
      selective D(2)-like agonist RU 24213 or the selective D(1)-like agonist SK and F
      83959. In contrast, D(5) mutants evidenced an increase in spontaneous vertical
      jaw movements, which habituated more slowly than in wildtypes, and a decrease in
      horizontal jaw movements; topographical responsivity to SK and F 83959 and RU
      24213 was unaltered. D(5) receptors regulate distinct topographies of vertical
      and horizontal jaw movement in an opposite manner. In assuming that the well
      recognised role of the D(1)-like family in regulating orofacial movements
      involves primarily D(1) receptors, a role for their D(5) counterparts may have
      been overlooked.

PMID- 16413759
TI  - Effects of exogenous p53 transfection on the gene expression in the human brain
      glioma cell line U251.
AB  - The p53 gene is activated in response to several malignancy-associated stress
      signals by transactivation of downstream genes and by transcription-independent
      mechanisms. In order to identify new p53 downstream genes, we established a new
      system of p53 gene inducible expression, U251-pTet-p53 cell line, with the Tet-On
      Gene Expression System, in which exogenous p53 gene could overexpress in
      doxycycline (Dox) medium but not in the medium without Dox. By comparing their
      random primer RT-PCR products, it was proved that exogenous p53 gene expression
      could lead to many genes differential expression, some up-expressed and others
      down-expressed. All of these differential expressed genes may be p53 downstream
      genes. We can gain the magnitude of p53 downstream genes, which provides the
      basis of directly cloning of novel p53 downstream genes and further studying of
      p53 regulatory network.

PMID- 16413760
TI  - Osmotic regulation of 10 wheat (Triticum aestivum L.) genotypes at soil water
      deficits.
AB  - Drought is a worldwide problem, seriously influencing plant (crop) productivity.
      Wheat is a stable food for 35% of the world population, moreover about 60% of
      land area on the globe belongs to arid and semi-arid zone. Wheat drought
      resistance is a multi-gene-controlling quantitative character and wheat final
      production in field is realized mainly by physiological regulation under the
      condition of multi-environmental factor interaction. Exploring drought resistance
      physiological mechanisms for different wheat genotypes is of importance to
      finding new drought resistance gene resources and conventional breeding and the
      basis for wheat drought resistance biotechnological breeding and platform.
      Osmotic adjustment regulation is the main component for physiological machinery
      of wheat drought resistance. By pot-cultivating experiments, investigation of
      osmotic adjustment comparison for 10 wheat genotypes at soil water deficits (75%
      FC, 55% FC, 45% FC, respectively), was conducted. The main results were as
      followed: (1) K(+) content in 10 wheat genotypes at three levels of soil water
      stress and at the same soil water deficit was very different. Five of these 10
      wheat genotypes had higher K K(+) content under the condition of 75% FC. (2) Five
      of these 10 wheat genotypes possessed greater soluble sugar content at 55% FC
      soil water level. (3) Proline (Pro) content in five wheat genotypes was higher at
      75% FC. (4) Five of these 10 wheat genotypes had lower malondialdehyde (MDA)
      content at 45% FC at seedling stage. Osmotic adjustment of wheat different
      genotypes was discussed in terms of different content of osmotic solutes.

PMID- 16413761
TI  - Analysis of surface properties of cellulose ethers and drug release from their
      matrix tablets.
AB  - Detailed knowledge based on new developments, especially in analytical
      techniques, is needed for characterizing polymer excipients. Inverse gas
      chromatography (IGC) is a useful method for investigating polymer surfaces in
      terms of thermodynamic parameters. The aim of our work was to study the
      correlation between polymer surface properties determined with IGC and the
      mechanisms of release of water-soluble pentoxifylline and vancomycin
      hydrochloride from cellulose ether matrices. Tablets were made of hydroxypropyl
      (HPC), hydroxyethyl (HEC) or hydroxypropylmethyl (HPMC) cellulose and contained
      25% of drug. Differences in dispersive component of the surface free energy for
      these polymers were relatively small and ranged from 26 to 33mN/m. However, polar
      properties, expressed as specific component of the enthalpy of adsorption and as
      acid-base properties show larger differences between the polymers and demonstrate
      their relative polarity in the order HEC>HPMC>HPC, which correlates well with
      water sorption on bulky polymers and with the swelling degree of polymer
      matrices. The release of pentoxifylline and vancomycin from HPC is governed
      mainly by Fickian diffusion, whereas from HEC the relaxation of polymer chains is
      important too. The analysis of the release profiles in the light of Peppas-Sahlin
      model lead to the conclusion that the surface properties of the cellulose ethers
      influence the interactions with water and the release mechanisms of the drug. It
      was found out, that data obtained by IGC enable rapid inference about the
      behaviour of polymers in water and the release of water-soluble drugs.

PMID- 16413762
TI  - Generic substitution: the use of medicinal products containing different salts
      and implications for safety and efficacy.
AB  - In their quest to gain early entry of new generic products into the market prior
      to patent expiration, one of the strategies pursued by generic drug product
      manufacturers is to incorporate different salts of an approved active
      pharmaceutical ingredient (API) in a brand company's marketed dosage form and
      subject such dosage forms to bioequivalence assessment. These initiatives present
      challenges to regulatory authorities where the decision to approve bioequivalent
      products containing such pharmaceutical alternatives must be considered in the
      light of safety and efficacy, and more particularly, with respect to their
      substitutability. This article describes the various issues and contentions
      associated with the concept of pharmaceutical alternatives, specifically with
      respect to the uses of different salts and the implications for safety, efficacy
      and generic substitution.

PMID- 16413763
TI  - [Clinical cases in dermatology].

PMID- 16413764
TI  - Bile acid transport and metabolism in rat liver slices.
AB  - To further characterise precision-cut liver slices from 34- to 40-day-old male
      rats as an in vitro model for bile acid (BA) metabolism and transport, the effect
      of the primary BAs cholic (CA, 5 microM) and chenodeoxycholic acid (CDCA, 0.15
      and 0.75 microM) as well as of the therapeutically used tauroursodeoxycholic acid
      (T-UDCA, 5 microM) on BA profiles was investigated. After 4 h incubation in 5 ml
      Krebs-Henseleit buffer (KHB) 26 individual BAs were determined in slices (50 mg
      liver/5 ml KHB) and medium by HPLC with postcolumn derivatisation and
      fluorescence detection. In control incubations, mean total BA concentrations were
      5.09 nmol/50 mg liver (101.80 nmol/g liver) in slices and 25.71 nmol/5 ml KHB,
      among them 72% taurine-(T-), 22% glycine-(G-) conjugated and 6% free BAs in
      tissue and medium. The main BAs were beta-muricholic (beta-MCA and conjugates)
      and cholic acids (CA and conjugates) in tissue and medium. The following results
      were obtained after addition of CDCA, CA, and T-UDCA, respectively, to the KHB.
      The toxic CDCA was quantitatively converted mainly to T-UDCA and
      taurohyodeoxycholic (T-HDCA) acid. CA was conjugated in equal shares to T- and G
      CA, whereas T-UDCA was enriched in slices and hydroxylated half to T-beta-MCA,
      which is the main BA in rats. In conclusion, rat liver slices are highly
      effective not only in uptake, conjugation and excretion of BAs but also in
      conversion of strong detergent into less toxic BAs.

PMID- 16413765
TI  - A new method of wet scanning electron microscopy for the analysis of myelination
      in EAE mouse model of multiple sclerosis.
AB  - Development of effective therapies for multiple sclerosis (MS) is dependent on
      the advancement of improved tools for evaluation of progression of this disease
      in animal models. We present a novel technique utilizing scanning electron
      microscopy (SEM) for imaging wet biological specimens thus enabling rapid and
      high-resolution imaging of myelin in mouse spinal cord (SC). We demonstrate the
      advantages of using the wet SEM technique to image myelin in a murine model of
      MS, experimental autoimmune encephalomyelitis (EAE) induced in the Biozzi
      (antibody-high) mouse, by sensitization with spinal cord homogenate (SCH) in
      adjuvant. Our studies show that the methodology allows easy identification of
      normal and pathological components with great clarity, which is then correlated
      with light microscopy (LM) and validated thereby. Furthermore, we demonstrate
      gold immunolabeling of specific epitopes. We conclude that the new technique
      provides a quick, accurate, and detailed structural evaluation of the SC that can
      be applied to advance the research of MS.

PMID- 16413766
TI  - Application of collagen matrices for cartilage tissue engineering.
AB  - Articular cartilage shows little capacity for self-repair once it has been
      damaged. The aim of this study was to investigate different collagen matrices
      regarding their applicability for cartilage tissue engineering. The matrices
      consist of collagen I and small amounts of elastine, were crosslinked with
      carbodiimide or glucose. Primary chondrocytes were seeded onto these different
      collagen matrices and cultured with or without differentiation medium. The
      viability of the cells was monitored via MTT test. The arrangement of the cells
      onto the scaffold was investigated by histological staining. Furthermore,
      extracellular matrix synthesis was studied by immunohistological staining,
      especially the expression of the typical chondrogenic marker collagen II.
      Moreover gene expression for collagen type II was analysed by RT-PCR. The
      chondrocytes showed high viability on all matrices used. The results for the
      histological staining revealed a three-dimensional arrangement of the
      chondrocytes in the collagen matrices. Moreover, the matrices also supported
      chondrogenic differentiation. On the matrix MATRIDERM 2 mm the synthesis of
      collagen II was stimulated without adding any differentiation supplements to the
      cell culture medium, as observed by immunohistological staining and by gene
      expression analysis of collagen II.

PMID- 16413767
TI  - Epidermal growth factor affects the synthesis and degradation of type I collagen
      in cultured human dermal fibroblasts.
AB  - EGF and type I collagen are known to play important roles in wound healing. In
      the present study, we demonstrated that EGF down-regulates the expression of type
      I procollagen protein as well as alpha2(I) collagen mRNA in cultured human dermal
      fibroblasts. EGF induced the degradation of type I procollagen protein in
      conditioned medium through the up-regulation of MMP-1 expression. EGF down
      regulated alpha2(I) mRNA expression partially at the post-transcriptional level
      by reducing the mRNA stability. In contrast, EGF up-regulated MMP-1 mRNA
      expression mostly at the transcriptional level, in that it had a stimulatory
      effect on MMP-1 promoter activity, but no effect on MMP-1 mRNA stability. The
      MEK/ERK signaling pathway was shown to be involved in EGF-mediated type I
      collagen and MMP-1 expression.

PMID- 16413768
TI  - Maltose-binding protein: a versatile platform for prototyping biosensing.
AB  - The bacterial periplasmic-binding protein (PBP) superfamily members, in
      particular the maltose-binding protein, have been used extensively to prototype a
      variety of biosensing platforms. Although quite diverse at the primary sequence
      level, this protein superfamily retains the same basic two-domain structure, and
      upon binding a recognized ligand almost all PBPs undergo a conformational change
      to a closed structure. This process forms the basis for most, but not all, PBP
      based biosensor signal transduction. Many direct detection or reagentless sensing
      modalities have been utilized with maltose-binding protein for both in vitro and
      in vivo detection of target compounds. Signal transduction modalities developed
      to date include direct fluorescence, electrochemical detection, fluorescence
      resonance energy transfer (FRET)-based detection, surface-tethered FRET sensing,
      hybrid quantum dot FRET sensing, and enzymatic detection, each of which have
      different benefits, potential applications and limitations.

PMID- 16413769
TI  - Studying plant-microbe interactions using stable isotope technologies.
AB  - Interactions between plants and microorganisms in the rhizosphere are complex and
      varied. They include the general transfer of nutrients and specific interactions
      mediated by the release of signalling molecules from plant roots. Until recently,
      understanding the nature of these interactions was limited by a reliance on
      traditional, cultivation-based techniques. Stable isotope probing provides the
      potential for cultivation-independent characterisation of organisms actively
      assimilating carbon derived from plant root exudate or added to the soil. Current
      applications have focused on interactions with relatively low-level specificity,
      but there is significant potential for mechanistic studies of more specific
      interactions, particularly if the sensitivity of the technique can be increased.

PMID- 16413770
TI  - Advances in optical detection strategies for reporter signal measurements.
AB  - Many recent advances in bioreporter technology focus on challenges related to
      bioengineering, yet in many applications implementation of optical signal
      measurement is equally susceptible to improvement. For bioluminescent
      bioreporters, one area of effort lies in the development of semiconductor chip
      based detector modules; this holds great promise for ultra-compact and field
      deployable instrumentation, but has not yet had a palpable impact on improved
      detection limits. Regarding lower detection limits, single-molecule detection
      techniques have seen their first application to bioreporters, and preliminary
      results serve as an indication of future promise. Another technique applicable to
      fluorescent bioreporters is fluorescence flow cytometry, which is rapid, suitable
      for high-throughput screening, and lends itself to increased analytical
      specificity through simple algorithmic approaches to data treatment.

PMID- 16413771
TI  - Secreted inducers in vertebrate eye development: more functions for old
      morphogens.
AB  - Cell signaling molecules secreted from strategically localized positions
      coordinate cell behavior to enable progressive specification of embryonic
      tissues. These molecules converge on a few signaling pathways that are
      reiteratively used in different tissues at different times for generating cell
      type-specific patterns of gene expression. Although our current knowledge of the
      system is fragmentary, eye development seems to follow this general strategy. In
      line with this idea, recent studies have added new information on how Fgf and Wnt
      signaling participates in the formation of the eye field. In addition, later on
      in development, Fgf controls the onset of retinal neurogenesis and Shh and GDF11
      control its feedback regulation.

PMID- 16413772
TI  - Network and graph analyses of folding free energy surfaces.
AB  - Protein folding is governed by a complex free energy surface whose entropic
      contributions are relevant because of the large number of degrees of freedom
      involved. Such complexity, in particular the conformational heterogeneity of the
      denatured state, is hidden in projections onto one or two order parameters (e.g.
      fraction of native contacts and/or radius of gyration), which usually results in
      relatively smooth surfaces. Recent approaches borrowed from network and graph
      theory have yielded quantitative unprojected representations of the free energy
      surfaces of a beta-hairpin and a three-stranded beta-sheet peptide using
      equilibrium folding-unfolding molecular dynamics simulations. Interestingly, the
      network and graph analyses of these structured peptides have revealed a very
      heterogeneous denatured state ensemble. It includes high-enthalpy, high-entropy
      conformations with fluctuating non-native secondary structure, as well as low
      enthalpy, low-entropy traps.

PMID- 16413773
TI  - Studies of folding and misfolding using simplified models.
AB  - Computer simulations are as vital to our studies of biological systems as
      experiments. They bridge and rationalize experimental observations, extend the
      experimental "field of view", which is often limited to a specific time or length
      scale, and, most importantly, provide novel insights into biological systems,
      offering hypotheses about yet-to-be uncovered phenomena. These hypotheses spur
      further experimental discoveries. Simplified molecular models have a special
      place in the field of computational biology. Branded as less accurate than all
      atom protein models, they have offered what all-atom molecular dynamics
      simulations could not--the resolution of the length and time scales of biological
      phenomena. Not only have simplified models proven to be accurate in explaining or
      reproducing several biological phenomena, they have also offered a novel
      multiscale computational strategy for accessing a broad range of time and length
      scales upon integration with traditional all-atom simulations. Recent computer
      simulations of simplified models have shaken or advanced the established
      understanding of biological phenomena. It was demonstrated that simplified models
      can be as accurate as traditional molecular dynamics approaches in identifying
      native conformations of proteins. Their application to protein structure
      prediction yielded phenomenal accuracy in recapitulating native protein
      conformations. New studies that utilize the synergy of simplified protein models
      with all-atom models and experiments yielded novel insights into complex
      biological processes, such as protein folding, aggregation and the formation of
      large protein complexes.

PMID- 16413774
TI  - Estradiol as an anti-aromatase agent in human breast cancer cells.
AB  - Estradiol (E(2)) is an important risk factor in the development and progression
      of breast cancer. However, a "direct effect" of E(2) in breast cancerization has
      not yet been demonstrated. The estrogen receptor complex can mediate the
      activation of oncogens, proto-oncogens, nuclear proteins and other target genes
      that can be involved in the transformation of normal to cancerous cells. Breast
      cancer cells possess all the enzymes (sulfatase, aromatase, 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD)) necessary for the local bioformation of E(2). In the
      last years, many studies have shown that treatment of breast cancer patients
      using anti-aromatase agents has beneficial therapeutic effects. The aromatase
      activity is very low in most breast cancer cells but was significantly increased
      in a hormone-dependent breast cancer cell line: the MCF-7aro, using the aromatase
      cDNA transfection and G-418 (neomycin) selection. In the present study, we
      explore the effect of E(2) on the aromatase activity of this cell line. The MCF
      7aro cell line was a gift from Dr. S. Chen (Beckman Research Institute, Duarte,
      U.S.A.). For experiments the cells were stripped of endogenous steroids and
      incubated with physiological concentrations of [(3)H]-testosterone (5 x 10(
      9)mol/l) alone or in the presence of E(2) (5 x 10(-5), 5 x 10(-7) and 5 x 10(
      9)mol/l) for 24h at 37 degrees C. The cellular radioactivity uptake was
      determined in the ethanolic supernatant and the DNA content in the remaining
      pellet. [(3)H]-E(2), [(3)H]-estrone ([(3)H]-E(1)) and [(3)H]-testosterone were
      characterized by thin layer chromatography and quantified using the corresponding
      standard. It was observed that [(3)H]-testosterone is converted mainly into
      [(3)H]-E(2) and not to E(1), which suggests very low or absence of oxidative
      17beta-HSD (type 2) activity in these experimental conditions. The aromatase
      activity, corresponding to the conversion of [(3)H]-testosterone to [(3)H]-E(2)
      after 24h, is relatively high, since the concentration of E(2) was 2.74+/
      0.11pmol/mg DNA in the non-treated cells. E(2) inhibits this conversion by 77, 57
      and 21%, respectively, at the concentrations of 5 x 10(-5), 5 x 10(-7) and 5 x
      10(-9)mol. In previous studies, it was demonstrated that E(2) exerts a potent
      anti-sulfatase activity in the MCF-7 and T-47D breast cancer cells. The present
      data show that E(2) can also block the aromatase activity. The dual inhibition of
      the aromatase and sulfatase activities, two crucial enzymes for the biosynthesis
      of E(2) by E(2) itself in breast cancer add interesting and attractive
      information for the use of estrogen therapeutic treatments.

PMID- 16413776
TI  - Sorption of zinc and lead on coir.
AB  - Pilot tests have shown that coir (fibres from Coco nucifera) is suitable as a
      metal ion sorbent. Batch sorption experiments were carried out with Zn and Pb to
      quantify the sorption kinetics, the pH dependence of the sorption, sorption
      isotherms at pH 3.0 and pH 5.6, and desorption. Unground and unmodified coir was
      used and the metal concentrations ranged between 0 and 0.015 mM (1000 microg/l)
      for Zn and 0 and 9.7 x 10(-4) M (200 microg/l) for Pb. The pH maximum was 4.5
      (91%) for Zn and 2.5 (97%) for Pb. Pb had a higher sorption affinity than Zn, and
      the affinity was higher at pH 5.6 than at pH 3.0. The isotherms could be
      represented by the Freundlich, but not by the Langmuir models in the
      concentration range tested. Desorption experiments demonstrated that less than 1%
      and 13% of the sorbed Pb and Zn, respectively, could be desorbed at pH 5.6 during
      2h.

PMID- 16413775
TI  - Characterization of the stimulatory effect of medroxyprogesterone acetate and
      chlormadinone acetate on growth factor treated normal human breast epithelial
      cells.
AB  - OBJECTIVE: Evidence is increasing that adding progestogens to hormone replacement
      therapy may be more harmful than beneficial, however it is debatable whether all
      progestogens act equally on breast cells. Mitogenic growth factors from stromal
      breast tissue are important in growth-regulation of breast cells, and may modify
      responses to progestogens. We investigated the effect of two C-21 derivatives,
      medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) on growth
      factor treated normal breast epithelial cells and tried to explore the underlying
      mechanisms of proliferation. METHOD: MCF10A (human epithelial, estrogen- and
      progesterone-receptor negative normal breast cells) were incubated with MPA or
      CMA at 0.1 and 1 microM for 7 days with the growth factors (GFs) EGF, bFGF and
      IGF-I at 1pM. The same combinations, as well as growth factors alone, were also
      incubated with the proliferation inhibitors PD98059 and LY294002 at 1 microM for
      4 days. Cell proliferation rate was measured by the ATP-assay. RESULTS: MPA 0.1
      and 1 microM, and CMA 1 microM in combination with GFs both significantly
      increased cell proliferation rate, with MPA having the greatest effect. MPA- and
      CMA-induced proliferation of GF stimulated cells was blocked by both PD98059
      (selective inhibitor of MAP kinases) and LY294002 (phosphatidylinositol 3-kinase
      inhibitor); GF stimulated cells could not be significantly reduced by any of the
      inhibitors used. CONCLUSION: MPA and CMA have a stimulatory effect on benign
      growth factor stimulated MCF10A cells, possibly via activation of MAP kinase and
      subsequent substrates and activation of PI3-kinase. GF induced proliferation
      appear to be mediated by pathways other than those investigated here. Growth
      factors and progestogens therefore have an additive, synergistic effect on cell
      proliferation, eliciting their effects via different pathways.

PMID- 16413777
TI  - Identification of a potent and selective non-basic cathepsin K inhibitor.
AB  - Based on our previous study with trifluoroethylamine as a P2-P3 amide isostere of
      cathepsin K inhibitor, further optimization led to identification of compound 22
      (L-873724) as a potent and selective non-basic cathepsin K inhibitor. This
      compound showed excellent pharmacokinetics and efficacy in an ovariectomized
      (OVX) rhesus monkey model. The volumes of distribution close to unity were
      consistent with this compound not being lysosomotropic, which is a characteristic
      of basic cathepsin K inhibitors.

PMID- 16413778
TI  - Discovery of novel and selective tertiary alcohol containing inhibitors of the
      norepinephrine transporter.
AB  - A novel series of tertiary alcohol containing 2-substituted benzyl morpholines
      have been discovered as potent and selective inhibitors of the norepinephrine
      transporter. Efficient synthetic routes were developed featuring a highly
      diastereoselective nucleophilic addition of benzyl Grignard reagents to
      enantiopure (4-benzylmorpholin-2-yl)phenylmethanone (11) as the key synthetic
      step. In vitro binding affinity for the norepinephrine, dopamine and serotonin
      transporters and in vivo examination of a select compound (16) in a
      pharmacodynamic animal model for norepinephrine reuptake inhibition are
      presented.

PMID- 16413779
TI  - Nuphar alkaloids with immediately apoptosis-inducing activity from Nuphar pumilum
      and their structural requirements for the activity.
AB  - The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar
      pumilum showed cytotoxic effects on human leukemia cell (U937), mouse melanoma
      cell (B16F10), and human fibroblast (HT1080). Dimeric sesquiterpene thioalkaloids
      with the 6-hydroxyl group (6-hydroxythiobinupharidine, 6,6'
      dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial
      cytotoxic activity at a concentration of 10 microM, but dimeric sesquiterpene
      thioalkaloids lacking the 6-hydroxyl group (thiobinupharidine, thionuphlutine B,
      6'-hydroxythionuphlutine B, neothiobinupharidine, thionuphlutine B beta
      sulfoxide, and neothiobinupharidine beta-sulfoxide) and monomeric sesquiterpene
      alkaloids (nupharidine, 7-epideoxynupharidine, and nupharolutine) showed weak
      activity. Next, apoptosis-inducing activity of a principal active constituent, 6
      hydroxythiobinupharidine, on U937 was examined using morphological observation
      and DNA fragmentation assay (TUNEL method). Apoptosis of U937 was immediately
      observed within 1 h after treatment of 6-hydroxythiobinupharidine at 2.5-10
      microM.

PMID- 16413781
TI  - Investigation of mechanism-based thrombin inhibitors: Implications of a highly
      conserved water molecule for the binding of coumarins within the S pocket.
AB  - The synthesis of novel coumarins bearing on the lateral side chain in the 3
      position an amine or a guanidine group is described. In vitro evaluation
      highlighted 14d which possesses a meta aniline side chain as a very potent THR
      inhibitor. Surprisingly, the introduction of a guanidine moiety always led to a
      decrease in THR inhibiting properties. We, thus, used docking experiments to
      rationalize the SAR in the series. This study showed the crucial role of a
      conserved water molecule in the specificity pocket of THR during docking
      simulation in order to explain the inactivity of guanidine derivatives.

PMID- 16413780
TI  - Synthesis and structure-activity relationship of 3,4'-bispyridinylethylenes:
      discovery of a potent 3-isoquinolinylpyridine inhibitor of protein kinase B
      (PKB/Akt) for the treatment of cancer.
AB  - Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led
      to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor
      with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity
      against distinct families of kinases such as tyrosine kinases and CAMK, and
      displays poor to marginal selectivity against closely related kinases in the AGC
      and CMGC families. Moreover, 13a demonstrates potent cellular activity comparable
      to staurosporine, with IC(50) values of 0.42 and 0.59microM against MiaPaCa-2 and
      the Akt1 overexpressing FL5.12-Akt1, respectively. Inhibition of phosphorylation
      of the Akt downstream target GSK3 was also observed in FL5.12-Akt1 cells with an
      EC(50) of 1.5microM. The X-ray structures of 12 and 13a in complex with PKA in
      the ATP-binding site were determined.

PMID- 16413782
TI  - 1-Phenyl-8-azabicyclo[3.2.1]octane ethers: a novel series of neurokinin (NK1)
      antagonists.
AB  - 1-Phenyl-8-azabicyclo[3.2.1]octane ethers are NK(1) receptor antagonists.
      Substitution at the 6-exo-position led to high affinity NK(1) antagonists with a
      prolonged duration of action in vivo. Incorporation of an alpha-methyl
      substituent in the pendent benzyl ether side chain gave compounds with increased
      selectivity over the hERG channel.

PMID- 16413783
TI  - Factor VIIa inhibitors: gaining selectivity within the trypsin family.
AB  - Within the trypsin family of coagulation proteases, obtaining highly selective
      inhibitors of factor VIIa has been challenging. We report a series of factor VIIa
      (fVIIa) inhibitors based on the 5-amidino-2-(2-hydroxy-biphenyl-3-yl)
      benzimidazole (1) scaffold with potency for fVIIa and high selectivity against
      factors IIa, Xa, and trypsin. With this scaffold class, we propose that a unique
      hydrogen bond interaction between a hydroxyl on the distal ring of the biaryl
      system and the backbone carbonyl of fVIIa lysine-192 provides a basis for
      enhanced selectivity and potency for fVIIa.

PMID- 16413784
TI  - Intra-session reliability of local dynamic stability of walking.
AB  - While local dynamic stability measures have been successfully used to
      characterize walking stability, they require long continuous walking data, which
      may be difficult to obtain from a clinical population. We investigated the amount
      of walking data necessary to obtain reliable measures of local dynamic stability.
      Twenty healthy adults walked on a motorized treadmill at their self-selected
      speed for three trials of 5 min each. Trunk motion was used to construct a 12
      dimensional state space comprised of the linear and angular positions and
      velocities. Mean divergence of locally perturbed trajectories was calculated as a
      measure of local dynamic stability using the first 1-5 min of data from each
      trial. Exponential divergence rates were quantified. Divergence was also
      parameterized using a double-exponential function. Intra-class correlation
      coefficients ICC(2,1) were calculated for each divergence measure for each trial
      length. ICC(2, 1) values increased with trial length, and reached 0.5-0.9. Good
      reliability was obtained for short-term measures for trial lengths of 2 and 3
      min, but 5 min was not adequate to estimate the long-term coefficients based on a
      single trial.

PMID- 16413785
TI  - New insights about HERG blockade obtained from protein modeling, potential energy
      mapping, and docking studies.
AB  - We created a homology model of the homo-tetrameric pore domain of HERG using the
      crystal structure of the bacterial potassium channel, KvAP, as a template. We
      docked a set of known blockers with well-characterized effects on channel
      function into the lumen of the pore between the selectivity filter and
      extracellular entrance using a novel docking and refinement procedure
      incorporating Glide and Prime. Key aromatic groups of the blockers are predicted
      to form multiple simultaneous ring stacking and hydrophobic interactions among
      the eight aromatic residues lining the pore. Furthermore, each blocker can
      achieve these interactions via multiple docking configurations. To further
      interpret the docking results, we mapped hydrophobic and hydrophilic potentials
      within the lumen of each refined docked complex. Hydrophilic iso-potential
      contours define a 'propeller-shaped' volume at the selectivity filter entrance.
      Hydrophobic contours define a hollow 'crown-shaped' volume located above the
      'propeller', whose hydrophobic 'rim' extends along the pore axis between Tyr652
      and Phe656. Blockers adopt conformations/binding orientations that closely mimic
      the shapes and properties of these contours. Blocker basic groups are localized
      in the hydrophilic 'propeller', forming electrostatic interactions with Ser624
      rather than a generally accepted pi-cation interaction with Tyr652. Terfenadine,
      cisapride, sertindole, ibutilide, and clofilium adopt similar docked poses, in
      which their N-substituents bridge radially across the hollow interior of the
      'crown' (analogous to the hub and spokes of a wheel), and project
      aromatic/hydrophobic portions into the hydrophobic 'rim'. MK-499 docks with its
      longitudinal axis parallel to the axis of the pore and 'crown', and its
      hydrophobic groups buried within the hydrophobic 'rim'.

PMID- 16413786
TI  - Chloroquine inhibits cell growth and induces cell death in A549 lung cancer
      cells.
AB  - To investigate the effects of chloroquine diphosphate (CQ) on lung cancer cell
      growth, we treated A549 cells, a lung cancer cell line, with the drug at various
      concentrations (0.25-128 microM) for 24-72 h. The results showed that, at lower
      concentrations (from 0.25 to 32 microM), CQ inhibited the growth of A549 cells
      and, at the same time, it induced vacuolation with increased volume of acidic
      compartments (VAC). On the other hand, at higher concentrations (64-128 microM),
      CQ induced apoptosis at 24 h, while its effect of inducing vacuolation declined.
      The lactate dehydrogenase (LDH) assay showed that with the treatment of CQ 32-64
      microM for 72 h or 128 microM for 48 h, CQ induced necrosis of A549 cells. To
      understand the possible mechanism by which CQ acts in A549 cells, we further
      incubated the cells with this drug at the concentrations of 32 or 128 microM in
      the presence of D609, a specific inhibitor of phosphatidylcholine-specific
      phospholipase C (PC-PLC). The results showed that D609 (50 microM) could inhibit
      the effects of CQ 32 microM on the viability and VAC, but it could not change the
      effects of CQ 128 microM on the same. Our data suggested that CQ inhibited A549
      lung cancer cell growth at lower concentrations by increasing the volume of
      lysosomes and that PC-PLC might be involved in this process. The data also
      indicated that, at higher concentrations, CQ induced apoptosis and necrosis, but
      at this time its ability to increase the volume of lysosome gradually declined,
      and PC-PLC might not be implicated in the process.

PMID- 16413787
TI  - Neamine derivatives having a nucleobase with a lysine or an arginine as a linker,
      their synthesis and evaluation as potential inhibitors for HIV TAR-Tat.
AB  - Neamine derivatives bearing a nucleobase, adenine, cytosine, guanine or thymine
      with a lysine or an arginine as a linker have been synthesized and its potential
      as the inhibitor for HIV TAR-Tat interaction examined. Among them, modified
      neamine having an arginine-nucleobase showed a higher inhibition than that of the
      one having a lysine-nucleobase. The difference of the nucleobase anchor did not
      characterize inhibition specificity. Also, stereochemistry of the amino acid in
      the compounds causes no difference in the inhibition for TAR-Tat.

PMID- 16413788
TI  - Nociceptor-derived brain-derived neurotrophic factor regulates acute and
      inflammatory but not neuropathic pain.
AB  - Conditional mouse knock-outs provide an informative approach to drug target
      validation where no pharmacological blockers exist or global knock-outs are
      lethal. Here, we used the Cre-loxP system to delete BDNF in most nociceptive
      sensory neurons. Conditional null animals were healthy with no sensory neuron
      loss. However, pain-related behavior was substantially altered. Baseline thermal
      thresholds were reduced. Carrageenan-induced thermal hyperalgesia was inhibited.
      Formalin-induced pain behavior was attenuated in the second phase, and this
      correlated with abolition of NMDA receptor NR1 Ser896/897 phosphorylation and
      ERK1 and ERK2 activation in the dorsal horn; AMPA receptor phosphorylation
      (GluR1/Ser831) was unaffected. NGF-induced thermal hyperalgesia was halved, and
      mechanical secondary hyperalgesia caused by intramuscular NGF was abolished. By
      contrast, neuropathic pain behavior developed normally. Nociceptor-derived BDNF
      thus plays an important role in regulating inflammatory pain thresholds and
      secondary hyperalgesia, but BDNF released only from nociceptors plays no role in
      the development of neuropathic pain.

PMID- 16413789
TI  - Mollusk shell formation: mapping the distribution of organic matrix components
      underlying a single aragonitic tablet in nacre.
AB  - Control over mineral formation in mollusk shells is exerted by the macromolecules
      of the organic matrix. Using histochemical methods, we mapped the carboxylates
      and sulfates of proteins and polysaccharides on the surfaces of decalcified
      interlamellar matrices from the nacreous shell layer of the cephalopod Nautilus
      pompilius, expanding upon an earlier study by Crenshaw and Ristedt [Crenshaw,
      M.A., Ristedt, H., 1976. The histochemical localization of reactive groups in
      septal nacre from Nautilus pompilius. In: Watabe, N., Wilbur, K.M. (Ed.), The
      Mechanisms of Mineralization in the Invertebrates and Plants. University of South
      Carolina Press, Colombia, pp. 355-367]. We observed four different zones
      underlying a single crystal: (1) a central spot rich in carboxylates; (2) a
      central ring-shaped area rich in sulfates; (3) an area between the central
      nucleation region and the imprint periphery containing carboxylates, and (4) the
      intertabular matrix, rich in carboxylates and sulfates. We also mapped matrix
      functional groups on the nacreous matrix surfaces of the bivalve Atrina rigida,
      but did not identify well-defined zones. Immuno-mapping of the constituents of
      the aragonite-nucleating protein fraction from Atrina nacre showed that these
      macromolecules are located both in the intertabular matrix and in the center of
      the crystal imprints for both Atrina and Nautilus matrix surfaces. Their presence
      at the latter location is consistent with their purported role in aragonite
      nucleation. The observed differentiation in the distribution of matrix components
      and their functional groups shows that the different stages of single crystal
      growth are highly controlled by the matrix.

PMID- 16413790
TI  - Assessment of the early organization and maturation of infants' cerebral white
      matter fiber bundles: a feasibility study using quantitative diffusion tensor
      imaging and tractography.
AB  - The human infant is particularly immature at birth and brain maturation, with the
      myelination of white matter fibers, is protracted until adulthood. Diffusion
      tensor imaging offers the possibility to describe non invasively the fascicles
      spatial organization at an early stage and to follow the cerebral maturation with
      quantitative parameters that might be correlated with behavioral development.
      Here, we assessed the feasibility to study the organization and maturation of
      major white matter bundles in eighteen 1- to 4-month-old healthy infants, using a
      specific acquisition protocol customized to the immature brain (with 15
      orientations of the diffusion gradients and a 700 s mm(-2)b factor). We were able
      to track most of the main fascicles described at later ages despite the low
      anisotropy of the infant white matter, using the FACT algorithm. This mapping
      allows us to propose a new method of quantification based on reconstructed
      tracts, split between specific regions, which should be more sensitive to
      specific changes in a bundle than the conventional approach, based on regions-of
      interest. We observed variations in fractional anisotropy and mean diffusivity
      over the considered developmental period in most bundles (corpus callosum,
      cerebellar peduncles, cortico-spinal tract, spino-thalamic tract, capsules,
      radiations, longitudinal and uncinate fascicles, cingulum). The results are in
      good agreement with the known stages of white matter maturation and myelination,
      and the proposed approach might provide important insights on brain development.

PMID- 16413791
TI  - Widespread functional connectivity and fMRI fluctuations in human visual cortex
      in the absence of visual stimulation.
AB  - To what extent does the visual system's activity fluctuate when no sensory
      stimulation is present? Here, we studied this issue by examining spontaneous
      fluctuations in BOLD signal in the human visual system, while subjects were
      placed in complete darkness. Our results reveal widespread slow fluctuations
      during such rest periods. In contrast to stimulus-driven activity, during
      darkness, functionally distinct object areas were fluctuating in unison. These
      fMRI fluctuations became rapidly spatially de-correlated (39% drop in correlation
      level, P < 0.008) during visual stimulation. Functional connectivity analysis
      revealed that the slow spontaneous fluctuations during rest had consistent and
      specific neuro-anatomical distribution which argued against purely hemodynamic
      noise sources. Control experiments ruled out eye closure, low luminance and
      mental imagery as the underlying sources of the spontaneous fluctuations. These
      results demonstrate that, when no stimulus is present, sensory systems manifest a
      robust level of slow organized fluctuation patterns.

PMID- 16413792
TI  - Category-specific effects in semantic memory: category-task interactions
      suggested by fMRI.
AB  - Much work has investigated the neural representation of specific categories of
      knowledge, but relatively scant attention has been paid in the cognitive
      neuroscience literature to the semantic processes that contribute to semantic
      memory. In this study, we monitored regional cortical activity with fMRI while
      healthy young adults evaluated visually displayed NATURAL KIND, ARTIFACT, and
      ABSTRACT nouns with two standard tasks: Typicality judgments and Pleasantness
      judgments. We observed a significant interaction effect between the category of
      knowledge and the type of judgment used to evaluate members of these semantic
      categories. Typicality judgments recruited greater temporal-occipital activation
      relative to Pleasantness judgments of the same category, and this was seen for
      comparisons of all three semantic categories. However, when contrasted with
      Typicality judgments, Pleasantness judgments activated a different anatomic
      distribution for each semantic category. These findings are consistent with a
      dynamic approach to semantic memory that includes at least two components:
      semantic knowledge and semantic processes that interpret this knowledge in
      several ways depending on the particular semantic challenge.

PMID- 16413793
TI  - A putative social chemosignal elicits faster cortical responses than perceptually
      similar odorants.
AB  - Social chemosignals, so-called pheromones, have recently attracted much attention
      in that effects on women's psychophysiology and cortical processing have been
      reported. We here tested the hypothesis that the human brain would process a
      putative social chemosignal, the endogenous steroid androstadienone, faster than
      other odorants with perceptually matched intensity and hedonic characteristics.
      Chemosensory event-related potentials (ERP) were recorded in healthy women. ERP
      analyses indicate that androstadienone was processed significantly faster than
      the control odorants. Androstadienone elicited shorter latencies for all recorded
      ERP components but most so for the late positivity. This finding indicates that
      androstadienone is processed differently than other related odorants, suggesting
      the possibility of a specific neuronal subsystem to the main olfactory pathway
      akin to the one previously reported in Old-world monkeys and emotional visual
      stimuli in humans.

PMID- 16413794
TI  - 3D MTR measurement: from 1.5 T to 3.0 T.
AB  - This study investigates some of the issues involved in magnetization transfer
      ratio (MTR) acquisition, and in particular aims to determine whether high quality
      in vivo MTR measurements can be made at 3.0 T. The dependency of the MTR white-to
      grey matter contrast to noise ratio (CNR) on MT pulse characteristics at 1.5 T
      and at 3.0 T was investigated using an established two-pool model for MT. The
      simulations showed that MT pulse parameters optimizing the CNR can be derived for
      both field strengths. Both the SNR and the CNR of MTR maps at 3.0 T were
      increased compared to 1.5 T. Images obtained using a safe in vivo MTR acquisition
      protocol based on results of simulations at 3.0 T are presented.

PMID- 16413795
TI  - How specifically do we learn? Imaging the learning of multiplication and
      subtraction.
AB  - The present functional magnetic resonance imaging (fMRI) study investigates
      modifications of brain activation patterns related to the training of two
      different arithmetic operations, multiplication and subtraction. Healthy young
      adults were trained in five sessions to answer multiplication and subtraction
      problems. In the following fMRI session, trained and new untrained problems
      closely matched for difficulty were presented in blocked order. Contrasts between
      untrained and trained operations showed stronger activation of inferior frontal
      and parietal regions, especially along the banks of the intraparietal sulcus. The
      reverse contrasts, trained minus untrained operations, yielded significantly
      higher activation in the left angular gyrus for multiplication but no
      significantly activated area for subtraction. This suggests that training leads
      to a reduction of general purpose processes, such as working memory and executive
      control in both operations, indicated by the decrease of activation in inferior
      frontal areas. For multiplication, however, the increase of activation in the
      left angular gyrus indicates a switching of cognitive processes. Trained
      subtraction therefore seems to lead to faster and more efficient strategies,
      while trained multiplication showed a shift from quantity-based processing
      (supported by the areas along the intraparietal sulci) to more automatic
      retrieval (supported by the left angular gyrus). The same training method caused
      changes in brain activation patterns that depended on the given operation. The
      effects of learning on the brain therefore seem not only to depend on the method
      of learning but also on its content.

PMID- 16413796
TI  - Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence
      processing.
AB  - The advent of functional neuroimaging has allowed tremendous advances in our
      understanding of brain-language relationships, in addition to generating
      substantial empirical data on this subject in the form of thousands of activation
      peak coordinates reported in a decade of language studies. We performed a large
      scale meta-analysis of this literature, aimed at defining the composition of the
      phonological, semantic, and sentence processing networks in the frontal,
      temporal, and inferior parietal regions of the left cerebral hemisphere. For each
      of these language components, activation peaks issued from relevant component
      specific contrasts were submitted to a spatial clustering algorithm, which
      gathered activation peaks on the basis of their relative distance in the MNI
      space. From a sample of 730 activation peaks extracted from 129 scientific
      reports selected among 260, we isolated 30 activation clusters, defining the
      functional fields constituting three distributed networks of frontal and temporal
      areas and revealing the functional organization of the left hemisphere for
      language. The functional role of each activation cluster is discussed based on
      the nature of the tasks in which it was involved. This meta-analysis sheds light
      on several contemporary issues, notably on the fine-scale functional architecture
      of the inferior frontal gyrus for phonological and semantic processing, the
      evidence for an elementary audio-motor loop involved in both comprehension and
      production of syllables including the primary auditory areas and the motor mouth
      area, evidence of areas of overlap between phonological and semantic processing,
      in particular at the location of the selective human voice area that was the seat
      of partial overlap of the three language components, the evidence of a cortical
      area in the pars opercularis of the inferior frontal gyrus dedicated to syntactic
      processing and in the posterior part of the superior temporal gyrus a region
      selectively activated by sentence and text processing, and the hypothesis that
      different working memory perception-actions loops are identifiable for the
      different language components. These results argue for large-scale architecture
      networks rather than modular organization of language in the left hemisphere.

PMID- 16413797
TI  - Distraction-spanning sustained activity during delayed recognition of locations.
AB  - This study investigated the neural systems that may make necessary contributions
      to the retention in working memory of location information. Particularly
      controversial in this regard have been the roles of various regions of frontal
      cortex. The task featured a multi-delay ABCA procedure designed to isolate target
      related delay-period activity that would be sustained across intervening,
      distracting stimuli. This property is necessary for fMRI signal from a brain area
      to be considered necessary for successful retention of target-related
      information. Across single-subject analyses and two different group analyses, the
      Frontal Eye Fields (FEF), Supplementary Eye Fields, and Intraparietal Sulcus were
      most reliably found to support multi-delay sustained activity, and effects tended
      to be more robust in left than right hemisphere. Such activity was not found
      reliably, however, in the Superior Frontal Sulcus anterior to the FEF nor in
      dorsolateral prefrontal cortex. These results are interpreted as inconsistent
      with memory systems accounts holding that certain frontal regions are specialized
      for spatial working memory functions. They are consistent, however, with the view
      that spatial working memory functions are the product of the operation of spatial
      selective attention and motor preparatory processes.

PMID- 16413798
TI  - EEG-fMRI of epileptic spikes: concordance with EEG source localization and
      intracranial EEG.
AB  - Simultaneous EEG and fMRI recordings permit the non-invasive investigation of the
      generators of spontaneous brain activity such as epileptic spikes. Despite a
      growing interest in this technique, the precise relationship between its results
      and the actual regions of activated cortex is not clear. In this study, we have
      quantified for the first time the concordance between EEG-fMRI results and
      stereotaxic EEG (SEEG) recordings in 5 patients with partial epilepsy. We also
      compared fMRI and SEEG with other non-invasive maps based on scalp EEG alone. We
      found that SEEG measures largely validated the results of EEG and fMRI. Indeed,
      when there is an intracranial electrode in the vicinity of an EEG or fMRI peak
      (in the range 20-40 mm), then it usually includes one active contact. This was
      the case for both increases ('activations') and decreases ('deactivations') of
      the fMRI signal: in our patients, fMRI signal decrease could be as important in
      understanding the complete picture of activity as increase of fMRI signal. The
      concordance between EEG and fMRI was not as good as the concordance between
      either of these non-invasive techniques and SEEG. This shows that the two
      techniques can show different regions of activity: they are complementary for the
      localization of the areas involved in the generation of epileptic spikes.
      Moreover, we found that the sign of the fMRI response correlated with the low
      frequency content of the SEEG epileptic transients, this latter being a
      reflection of the slow waves. Thus, we observed a higher proportion of energy in
      the low frequencies for the SEEG recorded in regions with fMRI signal increase
      compared to the regions with fMRI signal decrease. This could reflect an increase
      of metabolism linked to the presence of slow waves, which suggests that fMRI is a
      new source of information on the mechanisms of spike generation.

PMID- 16413799
TI  - A review of the effects of insulin-like growth factor and platelet derived growth
      factor on in vivo cartilage healing and repair.
AB  - Growth factors may enhance current cartilage repair techniques via multiple
      mechanisms including recruitment of chondrogenic cells (chemotaxis), stimulation
      of chondrogenic cell proliferation (mitogenesis) and enhancement of cartilage
      matrix synthesis. Two growth factors that have been studied in cartilage repair
      are insulin-like growth factor (IGF) and platelet derived growth factor (PDGF).
      IGF plays a key role in cartilage homeostasis, balancing proteoglycan synthesis
      and breakdown. Incorporating IGF into a fibrin clot placed in an equine cartilage
      defect improved the quality and quantity of repair tissue and reduced synovial
      inflammation. PDGF is a potent mitogenic and chemotactic factor for all cells of
      mesenchymal origin, including chondrocytes and mesenchymal stem cells. Resting
      zone chondrocytes cultured with PDGF demonstrated increased cell proliferation
      and proteoglycan production, while maturation of these cells along the
      endochondral pathway was inhibited. Pretreating chondrocytes with PDGF promotes
      heterotopic cartilage formation in the absence of any mechanical stimulus. PDGF
      has also been shown to be a potent stimulator of meniscal cell proliferation and
      migration. These studies and others suggest a potential role for these potent
      biological regulators of chondrocytes in cartilage repair. More work needs to be
      performed to define their appropriate dosing and the optimum delivery method.
      Combining tissue growth factors with a biological matrix can provide a physical
      scaffold for cell adhesion and growth as well as a means to control the release
      of these potent molecules. This could result in biological devices that enhance
      the predictability and quality of current cartilage repair techniques.

PMID- 16413800
TI  - The vascular surgeon facing clinical ethical dilemmas (the VASCUETHICS Study):
      'V'-shaped association between compassionate attitudes and professional
      seniority.
AB  - OBJECTIVE: To evaluate the association between compassionate attitudes and
      seniority in vascular surgeons facing clinical ethical dilemmas (CED). SUBJECTS
      AND METHODS: (1) DESIGN: Cross-sectional. (2) SUBJECTS: Vascular surgeons
      (residents included) from the 28 vascular teaching departments of one European
      country. (3) MEASUREMENTS: Multidisciplinary team-designed, structured and self
      administered questionnaire consisting of five clinical ethical dilemmas, of which
      four had conflict between compassion towards a 'small' or 'very costly'
      beneficial action vs. a reasonable but more 'pragmatic' allocation of health
      resources. Participants stated their degree of agreement with eight answers
      representing the two attitudes on a continuous scale. (4) STATISTICS: Cluster
      analysis and logistic regression model adjusted by confounding factors. RESULTS:
      Two hundred and fifty three vascular surgeons (median age 37 years, 74% male)
      from the 26 participating teaching vascular departments (public hospitals)
      completed the questionnaire (88% surgeons/department). Cluster analysis
      identified two groups of surgeons according to their pattern of answers: Group I
      (n=63) were mainly compassionate whereas Group II (n=180) were mainly pragmatic.
      The multivariate analysis disclosed, after adjusting for additional private
      practice, on call services and career status, a significant V-shaped relationship
      between the compassionate behaviour and seniority. Surgeons with 8-15 years
      experience were the least compassionate. CONCLUSIONS: The youngest and the most
      senior vascular surgeons were more prone to favour compassionate attitudes when
      facing clinical ethical dilemmas. Although both compassionate and pragmatic
      attitudes may be legitimate ethically, physicians not favouring compassion may be
      at risk of leaving the patient without an advocate within the health care system.

PMID- 16413801
TI  - Prevalence of pain in adults admitted to Catalonian hospitals: a cross-sectional
      study.
AB  - OBJECTIVE: To survey the prevalence of pain in patients admitted to different
      hospitals of Catalonia and to describe which factors are related to pain.
      METHODS: A cross-sectional study was performed in 1675 patients from fifteen
      hospitals in Catalonia (Spain). Clinical and demographic data, as well as the
      existence of pain intensity evaluations and analgesic therapy, were obtained from
      medical charts. Characteristics of pain were given by patients after being
      interviewed by trained interviewers. The main-outcome measure was the existence
      of pain (at the interview, in the previous 24h, at the admission and at any time
      after admission) that was assessed by a visual analogue scale (VAS). The
      relationship of prevalence of pain to patients' characteristics was carried out
      by means of a multiple-logistic-regression model with pain presence as the
      dependent variable of interest. RESULTS: A great variability in the prevalence
      and intensity of pain among different hospitals was observed. At the time of the
      interview, 48.5% (95% CI: 46.1-50.9%) of the patients had pain and the median VAS
      was 40mm (range: 10-100mm), and the prevalence of pain during the previous 24h
      was similar (47.6%; 95% CI: 45.2-50%). At admission, 26.7% (95% CI: 24.6-28.8%)
      of patients were in pain, whereas 62% (95% CI: 59.7-64.3%) reported having pain
      at some time during their stay. Pain intensity annotations were absent in 51.3%
      (95% CI: 47.9-54.7%) of the medical records of the patients with pain. The
      factors associated with pain were younger age, female gender, presence of
      surgery, orthopaedic surgery wards, large hospital and prescribed analgesics.
      CONCLUSION: A high prevalence of clinically relevant pain in in-patients was
      found as well as a great variability according to type of patients, clinical
      wards and hospitals. This study gives clear evidence of the lack of adequate
      management of pain in the majority of the hospitals and calls for the
      implementation of organisational and educational measurements that may settle
      this epidemic problem.

PMID- 16413802
TI  - Optimal control design of constant amplitude phase-modulated pulses: application
      to calibration-free broadband excitation.
AB  - An optimal control algorithm for generating purely phase-modulated pulses is
      derived. The methodology is applied to obtain broadband excitation with
      unprecedented tolerance to RF inhomogeneity. Design criteria were transformation
      of Iz-->Ix over resonance offsets of +/-25 kHz for constant RF amplitude anywhere
      in the range 10-20 kHz, with a pulse length of 1 ms. Simulations transform Iz to
      greater than 0.99 Ix over the targetted ranges of resonance offset and RF
      variability. Phase deviations in the final magnetization are less than 2-3
      degrees over almost the entire range, with sporadic deviations of 6-9 degrees at
      a few offsets for the lowest RF (10 kHz) in the optimized range. Experimental
      performance of the new pulse is in excellent agreement with the simulations, and
      the robustness of the excitation pulse and a derived refocusing pulse are
      demonstrated by insertion into conventional HSQC and HMBC-type experiments.

PMID- 16413803
TI  - Molecular modeling, docking and ADMET studies applied to the design of a novel
      hybrid for treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia in adults, which is
      characterized by senile plaquets and cholinergic deficit as the disease
      progresses. Improvement of cholinergic neurotransmission is the basis of some
      drugs currently used in the treatment of AD. It is achieved by
      acetylcholinesterase (AChE) inhibition, the enzyme responsible for acetylcholine
      hydrolysis. Molecular modeling techniques were of utmost importance to design a
      new pharmaceutical against Alzheimer's disease, with potential inhibitory
      activity over AChE, since the inhibition of human plasma butyrylcholinesterase
      (BChE) may cause side effects. Some of the drugs currently used in the treatment
      of AD are capable of increasing the cholinergic transmission through the AChE
      inhibition. In this work we proposed molecular hybrids of tacrine with donepezil
      (fusion of these structures), in order to suggest new proposals of AChE
      inhibitors for future treatment of AD. We have analyzed all the structures by
      docking, density functional studies and drug like properties.

PMID- 16413804
TI  - Effects of high-pressure acclimatization on silver eel (Anguilla anguilla, L.)
      slow muscle contraction.
AB  - As the spawning migration of the eel is supposed to correspond to a long swimming
      activity at depth, patterns of slow red muscle contraction have been investigated
      in European silver eel (Anguilla anguilla L.) exposed for 3 weeks to 10.1 MPa
      hydrostatic pressure. The results show that pressure-acclimated eels (male and
      female) show a three-fold decrease in maximum isometric stress of twitch and
      tetanic contractions while time to peak force, time from peak force to 90%
      relaxation and ratio of twitch tension to tetanic tension remain unchanged. The
      observed modifications in slow red muscle mechanical properties do not impede the
      spawning migration of the eel and are possibly partially compensated by an
      improvement in the efficiency of oxidative phosphorylation. Effects of changes in
      membrane fluidity are also discussed.

PMID- 16413805
TI  - Neuroendocrinology of protochordates: insights from Ciona genomics.
AB  - The genome for two species of Ciona is available making these tunicates excellent
      models for studies on the evolution of the chordates. In this review most of the
      data is from Ciona intestinalis, as the annotation of the C. savignyi genome is
      not yet available. The phylogenetic position of tunicates at the origin of the
      chordates and the nature of the genome before expansion in vertebrates allows
      tunicates to be used as a touchstone for understanding genes that either preceded
      or arose in vertebrates. A comparison of Ciona, a sea squirt, to other model
      organisms such as a nematode, fruit fly, zebrafish, frog, chicken and mouse shows
      that Ciona has many useful traits including accessibility for embryological,
      lineage tracing, forward genetics, and loss- or gain-of-function experiments. For
      neuroendocrine studies, these traits are important for determining gene function,
      whereas the availability of the genome is critical for identification of ligands,
      receptors, transcription factors and signaling pathways. Four major neurohormones
      and their receptors have been identified by cloning and to some extent by
      function in Ciona: gonadotropin-releasing hormone, insulin, insulin-like growth
      factor, and cionin, a member of the CCK/gastrin family. The simplicity of
      tunicates should be an advantage in searching for novel functions for these
      hormones. Other neuroendocrine components that have been annotated in the genome
      are a multitude of receptors, which are available for cloning, expression and
      functional studies.

PMID- 16413806
TI  - Effects of atorvastatin on lipid metabolism in normolipidemic and hereditary
      hyperlipidemic, non-laying hens.
AB  - As a result of a hereditable point mutation in the oocyte very low density
      lipoprotein (VLDL) receptor, sexually mature restricted ovulator (RO) female
      chickens (Gallus gallus), first described as a non-laying strain, exhibit
      endogenous hyperlipidemia and develop atherosclerotic lesions. In a 20-day study,
      RO hens and their normolipidemic (NL) siblings were fed either a control diet, or
      the control diet supplemented with 0.06% atorvastatin (AT), a potent 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMGR) inhibitor. Compared to NL hens, RO
      birds exhibited greatly elevated baseline plasma total cholesterol (CHOL) and
      triglyceride (TG) concentrations (1.56 vs. 4.55 g/l and 30.7 vs. 138.4 g/l,
      respectively). AT attenuated plasma CHOL and TG concentrations by 60.3% and
      70.1%, respectively, in NL hens and by 45.1% and 34.3%, respectively, in RO hens.
      Messenger RNA levels of several key genes involved in hepatic VLDL assembly were
      suppressed in RO vs. NL hens, but were unaffected by AT. In contrast, AT elevated
      liver HMGR mRNA levels in NL and RO birds, but only NL hens exhibited an AT
      associated increase in hepatic HMGR immunoreactive protein levels. Down
      regulation of HMGR gene expression due to higher baseline levels of circulating
      CHOL may explain why RO birds responded less robustly than NL hens to AT
      administration.

PMID- 16413807
TI  - Arginine vasotocin (AVT) and isotocin (IT) in fish brain: diurnal and seasonal
      variations.
AB  - An HPLC assay with solid-phase extraction and fluorescence derivatization was
      developed for measurement of arginine vasotocin (AVT) and isotocin (IT) in the
      neural tissues of fish. The efficiency and usefulness of the method have been
      verified in experiments by examination of peptides concentrations in brains of
      three fish species. The day-night changes in neuropeptides levels have been
      studied in brains of adult sea bream (Sparus aurata) and juvenile Atlantic salmon
      (Salmo salar). Seasonal fluctuations have been investigated in brains of three
      spined sticklebacks (Gasterosteus aculeatus). The AVT and IT biosynthesis in
      brain seems to be controlled independently and probably each neuropeptide plays a
      different role in a circadian time-keeping system and an endocrine calendar in
      fish.

PMID- 16413808
TI  - WITHDRAWN: Identification of four evolutionarily related G-protein-coupled
      receptors from the malaria mosquito Anopheles gambiae.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 16413810
TI  - [Laparoscopic treatment of borderline ovarian tumor: analysis of 54 patients and
      clinical outcomes. Gynecol Obstet Fertil 2005;33:395-402].

PMID- 16413809
TI  - Metabolic engineering under uncertainty--II: analysis of yeast metabolism.
AB  - Yeast metabolism has been used extensively in scientific investigations and
      industrial applications. Understanding the properties of the yeast metabolic
      network is crucial, yet unaccomplished due to its high complexity, the different
      culture conditions, and the uncertainty associated with kinetic parameters. We
      recently developed a computational and mathematical framework using Monte Carlo
      method in which parameter uncertainty can be addressed through large-scale
      sampling procedure. This framework was applied on the compartmentalized central
      carbon pathways of Saccharomyces cerevisiae metabolism considering the growth
      environment of batch and chemostat reactor and integrating information from
      metabolic flux analysis. Statistical analysis of the results indicates that yeast
      cells growing in batch culture condition exhibit dramatically different control
      schemes from those growing in a chemostat. The difference is mainly due to the
      feedback introduced by the constraints of the chemostat. The control of the
      enzymes on the rates of the substrate uptake, product excretion, and cell growth
      and its practical implication are discussed. Clustering of the reaction steps
      according to the similarity of their responses to enzyme activity perturbations
      reveals functional coupling of metabolic reactions.

PMID- 16413811
TI  - [Cervical ripening using misoprostol before hysteroscopy].
AB  - Cervical ripening with misoprostol is performed before office or operative
      hysteroscopy. Aim of this review is to evaluate benefits of cervical ripening
      with misoprostol before hysteroscopy . Ten studies were selected concerning
      office or operative hysteroscopy. Cervical ripening with misoprostol seems to be
      not useful for office hysteroscopy performed with minihysteroscope. Interest of
      misoprostol in menopausal women with traditional office hysteroscope is
      debatable. Risk of cervical tear during operative hysteroscopy seems to be
      reducing with misoprostol. However, interest of misoprostol was not found in all
      studies. Data were not sufficient to determine adequate dose of misoprostol, time
      and mode of administration. However, vaginal administration is preferable.

PMID- 16413812
TI  - A case of sudden death after intramuscular injection of butylscopolamine bromide.
AB  - A 40-year-old man experienced cardiopulmonary arrest after intramuscular
      injection of 20 mg of butylscopolamine bromide. No pathological changes were
      found at autopsy, and 1.19 microg/mL of butylscopolamine bromide was detected in
      his serum. Since he had taken no other drugs, his severe symptoms were thought to
      have been caused by an anaphylactic reaction to butylscopolamine bromide.
      Butylscopolamine bromide has been used for many years worldwide, and is
      considered to be a safe drug, with no reports of severe side effects following
      intramuscular injection. Since an anaphylactic reaction may not be related to a
      particular medication, the possibility of such a severe reaction must be
      considered, even during administration of an ostensibly safe drug such as
      butylscopolamine bromide.

PMID- 16413813
TI  - Forensic value of nine STR loci in Northern Thai.
AB  - Nine STR loci (D3S1358, D5S818, D7S820, D8S1179, D13S317, TH01, VWA, TPOX, LPL)
      were studied in a large Northern Thai population sample. All loci meet Hardy
      Weinberg expectations. The combined power of discrimination and exclusion is
      0.9999999979 and 0.99798 respectively. Mutation rates for STR loci did not exceed
      1-4 per 1000 parent/child pairs as derived from disputed paternity cases. Similar
      mutation rates were also reported from other populations. No mutations were found
      for D5S818, D7S820, TH01, and TPOX.

PMID- 16413815
TI  - Triage test and HPLC assay for analysis of vegetamin, an antipsychotic agent,
      using gastric contents and blood specimens.
AB  - Vegetamin is an antipsychotic agent composed of phenobarbital, promethazine and
      chlorpromazine. While phenobarbital can be detected by the Triage kit for
      screening drugs of abuse, the other two components cannot. We describe here the
      detection of promethazine and chlorpromazine using either a high performance
      liquid chromatography (HPLC) unit equipped with an ultraviolet, a photodiode
      array (PDA), or an electrochemical detector (ECD), or gas chromatograph-mass
      spectrometry (GC-MS). The absorption and mass spectra of promethazine and
      chlorpromazine were nonspecific, and thus the ECD-HPLC system was best equipped
      to quantitate these components. Comparison of the chromatograms of blood and
      gastric contents aids the identification of drug metabolites.

PMID- 16413814
TI  - Postmortem cardiac troponin T levels in the blood and pericardial fluid. Part 2:
      analysis for application in the diagnosis of sudden cardiac death with regard to
      pathology.
AB  - Although previous forensic pathological studies have suggested the possible
      application of cardiac troponins in the diagnosis of myocardial infarction, there
      appears to be insufficient data with regard to its cardiac pathology. The present
      study analyzed the heart blood, peripheral blood and pericardial fluid levels of
      cardiac troponin T (cTnT) in sudden cardiac deaths (n = 96) within 48h postmortem
      in relation to pathological findings of acute myocardial infarction (AMI, n =
      34), recurrent myocardial infarction (RMI, n = 23), ischemic heart disease
      without any pathological evidence of infarction (IHD, n = 24) and other heart
      diseases (OHD, n = 15). Control groups (n = 75, survival time <24 h) within 48 h
      postmortem consisted of asphyxiation (n = 35), drowning (n = 27) and
      cerebrovascular diseases (n = 13). There was a marked correlation in the cTnT
      levels between right and left heart blood samples. The pericardial level was
      usually higher than either heart blood level, and the external iliac venous blood
      level was the lowest. Although postmortem time-dependent increases in heart and
      pericardial blood cTnT levels were observed in most groups, they were most
      evident for AMI and asphyxiation. In the early postmortem period (<12 h) there
      was no significant difference between AMI or RMI and the other groups except for
      drowning. After 12 h postmortem, significantly elevated heart blood and
      pericardial cTnT levels were observed for AMI and RMI showing multiple
      interstitial hemorrhages and necrosis compared to those with localized
      eosinophilic changes or patchy interstitial hemorrhages, IHD and OHD. These
      differences were the smallest for peripheral blood. For sudden cardiac death
      cases, the difference in cTnT level at each site among the causes of death was
      independent of gender, age, heart or lung weight and pathologies of affected
      coronary artery and severity of coronary stenosis. These observations suggest
      that the elevation in postmortem blood and pericardial cTnT levels in sudden
      cardiac death may depend on the severity of ischemic myocardial damage including
      the size and intensity of myocardial lesions involving multiple interstitial
      hemorrhages and necrosis, and also the postmortem period for heart and
      pericardial levels.

PMID- 16413816
TI  - Nanoparticles: potential biomarker harvesters.
AB  - A previously untapped bank of information resides within the low molecular weight
      proteomic fraction of blood. Intensive efforts are underway to harness this
      information so that it can be used for early diagnosis of diseases such as
      cancer. The physicochemical malleability and high surface areas of nanoparticle
      surfaces make them ideal candidates for developing biomarker harvesting
      platforms. Given the variety of engineering strategies afforded through
      nanoparticle technologies, a significant goal is to tailor nanoparticle surfaces
      to selectively bind a subset of biomarkers, sequestering them for later study
      using high sensitivity proteomic tests. To date, applications of nanoparticles
      have largely focused on imaging systems and drug delivery vectors. As such,
      biomarker harvesting is an underutilized application of nanoparticle technology
      and is an area of nanotechnology research that will likely undergo substantial
      growth.

PMID- 16413817
TI  - Molecular and functional analysis using live cell microarrays.
AB  - Understanding cellular behavior in both healthy and diseased states requires the
      ability to molecularly delineate the characteristics of individual cells from
      complex mixtures. The recent development of cellular microarrays allows such an
      undertaking. By immobilizing different cell capture and analysis reagents on a
      solid support, mixtures of cells can be rapidly interrogated for their
      composition and phenotype. Thus, one can identify and quantitate distinct cell
      types based on the expression of particular cell surface molecules, as well as
      analyze their response to defined signals through the secretion of specific
      factors or other measurable cellular activities. This review focuses on the use
      of cellular microarrays to detect antigen-specific T cells and their
      responsiveness, analyze cancer cell types and behavior and to investigate the
      control of stem cell differentiation.

PMID- 16413818
TI  - Yersinia's stratagem: targeting innate and adaptive immune defense.
AB  - In contrast to Salmonella and Shigella, enteropathogenic Yersinia species are
      extracellular multiplying Gram-negative bacteria. This life style requires a
      sophisticated anti-host strategy, which is implemented by the Yersinia virulence
      plasmid. This plasmid encodes the type 3 secretion system (injectisome), at least
      six microinjected anti-host effector proteins, a trimeric coiled coil outer
      membrane protein (Yersinia adhesin) with cell adhesin and protective functions
      against complement and defensins, and the released V antigen, which has Toll-like
      receptor 2 agonist activity.

PMID- 16413819
TI  - A flow cytometry-optimized assay using an SOS-green fluorescent protein (SOS-GFP)
      whole-cell biosensor for the detection of genotoxins in complex environments.
AB  - Whole-cell biosensors have become popular tools for detection of ecotoxic
      compounds in environmental samples. We have developed an assay optimized for flow
      cytometry with detection of genotoxic compounds in mind. The assay features
      extended pre-incubation and a cell density of only 10(6)-10(7) cells/mL, and
      proved far more sensitive than a previously published assay using the same
      biosensor strain. By applying the SOS-green fluorescent protein (GFP) whole-cell
      biosensor directly to soil microcosms we were also able to evaluate both the
      applicability and sensitivity of a biosensor based on SOS-induction in whole soil
      samples. Soil microcosms were spiked with a dilution-series of crude broth
      extract from the mitomycin C-producing streptomycete Streptomyces caespitosus.
      Biosensors extracted from these microcosms after 1 day of incubation at 30
      degrees C were easily distinguished from extracts of non-contaminated soil
      particles when using flow cytometry, and induction of the biosensor by mitomycin
      C was detectable at concentrations as low as 2.5 ng/g of soil.

PMID- 16413820
TI  - Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced
      DNA damage as shown by the comet assay technique.
AB  - Aloysia triphylla a perennial, bushy plant originally from South America has long
      been used in traditional medicine. Its aqueous extract contains considerable
      amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view
      of the interest in natural phenolic compounds as antioxidant in preventive
      medicine, this study was undertaken to investigate the chemoprotective effects of
      cedron leaves infusion against the genetic damage induced by acrylamide (AA) by
      using the alkaline version of the comet assay technique. Mice were separated in
      nine groups (eight animals each): (I) untreated, (II) negative control, (III)
      treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with
      AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30
      mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with
      infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control
      (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally
      evaluated per animal from three different slides (100 each). Media of tail moment
      (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were
      found between untreated animals, negative control and infusion-treated mice. A
      single dose of AA-induced genetic damage as revealed by a statistically
      significant increase in TM values (p<0.01). Pretreatment with infusion prior to
      AA injection significantly reduces the capacity of AA to induce genetic damage.
      In these conditions, tail moments values did not differ from data obtained in
      negative control (p>0.05) and exhibit statistical differences from animals
      treated only with AA (p<0.01). Cell viability was at least 90% in all cases as
      measured by the trypan blue exclusion method. The ferric reducing ability of
      plasma (FRAP) method reveals that the plasma of infusion-treated mice has a
      significantly higher antioxidant capacity than plasma from controls (p<0.01). The
      results suggest that the infusion could exerts an in vivo chemo protective
      action, probably due to its scavenging potency towards free radicals.

PMID- 16413821
TI  - Potential of chlorpyrifos and cypermethrin forming DNA adducts.
AB  - DNA adducts consist of DNA monoadducts, DNA intrastrand crosslinks, DNA
      interstrand crosslinks, and DNA-protein crosslinks. If not repaired or mistakenly
      repaired, DNA adducts may lead to gene mutations and initiate carcinogenesis. Two
      insecticides, chlorpyrifos and cypermethrin, were studied for their potential of
      forming DNA monoadducts, DNA interstrand crosslinks, and DNA-protein crosslinks
      in primary mouse hepatocytes via the assays of bioluminescence, ethidium bromide
      fluorescence, and K+-SDS precipitation. DNA interstrand crosslinks were also
      measured on calf thymus DNA. It was shown that chlorpyrifos could not form DNA
      adducts. Cypermethrin formed DNA monoadducts and DNA interstrand crosslinks in
      hepatocytes. However, cypermethrin didn't form DNA interstrand crosslinks on calf
      thymus DNA and in hepatocytes treated with SKF-525A, a cytochrome P450 inhibitor,
      which suggests that active metabolites of cypermethrin instead of cypermethrin
      itself caused DNA interstrand crosslinks and that cytochrome P450 may be involved
      in the activation of cypermethrin.

PMID- 16413822
TI  - Hepatitis E virus infection in wild mongooses of Okinawa, Japan: Demonstration of
      anti-HEV antibodies and a full-genome nucleotide sequence.
AB  - Hepatitis E virus (HEV), a single-strand RNA virus, has been recovered not only
      from human beings but also from various species of animals. Here we report our
      results suggesting that mongoose should be added to the list of reservoir animals
      of HEV. Of 100 mongooses we examined in Okinawa, Japan, 21 were thought to be
      positive for anti-HEV antibodies, among which one was definitely positive for HEV
      RNA. Full-genome sequencing of the HEV isolate revealed that it segregates to a
      unique subgroup within genotype III. Interestingly, this mongoose strain was
      closely related to a swine isolate previously reported from Okinawa, implicating
      the possibility of interspecies transmission between these animals.

PMID- 16413823
TI  - Would monitoring CMV immune responses allow improved control of CMV in stem cell
      transplant patients.
AB  - BACKGROUND: Virological monitoring with sensitive assays and subsequent
      introduction of antiviral preemptive therapy has become a routine strategy in the
      management of stem cell transplant recipients. Several techniques have been used
      and each has advantages and disadvantages. OBJECTIVE: The objective of this
      review is to discuss the drawbacks of virological monitoring alone for the
      management of CMV in stem cell transplant recipients. STUDY DESIGN: Publications
      on the success of CMV viral load monitoring were reviewed with special emphasis
      on the timing of CMV disease after stem cell transplantation. RESULTS AND
      CONCLUSIONS: During recent years CMV disease has more frequently been documented
      later after transplantation and has been associated with the absence of CMV
      specific immune responses. Repeated antiviral therapy carries the risk of
      toxicity and the development of resistance. Hence virological monitoring might be
      insufficient for optimal management of these patients. This realization has
      spurred interest in evaluating assays for immunological monitoring as a means of
      improving control of potential CMV disease after transplantation.

PMID- 16413824
TI  - Prediction of endothelial cell tropism of human cytomegalovirus strains.

PMID- 16413825
TI  - CMV as a cofactor enhancing progression of AIDS.
AB  - BACKGROUND: Cytomegalovirus (CMV) has been proposed as a cofactor driving HIV
      pathogenicity since the late 1980s. Potential mechanisms which CMV could use as a
      cofactor have been described in vitro and potential criteria for assessing
      cofactor activity in vivo have been proposed. OBJECTIVE: To determine if recent
      publications have added new information to these in vitro or in vivo studies
      since the author last reviewed this subject in 1998. STUDY DESIGN: Literature
      survey prior to presenting an overview lecture. RESULTS: No new in vitro
      mechanisms have been described though several clinical cohort studies are
      consistent with the possibility that active CMV infection can act as a cofactor.
      One study published in 1999 showed that mortality in AIDS patients was driven
      more by CMV viral load than HIV viral load. Although highly active antiretroviral
      therapy (HAART) has now greatly controlled end organ disease caused by CMV, a
      recent study showed that CMV viraemia was still strongly associated with death in
      AIDS patients. CONCLUSIONS: (1) CMV remains important in the era of HAART. (2)
      CMV has been underestimated as an important cofactor since the beginning of the
      AIDS epidemic.

PMID- 16413826
TI  - Classification of single MEG trials related to left and right index finger
      movements.
AB  - OBJECTIVE: Most non-invasive brain-computer interfaces (BCIs) classify EEG
      signals. Here, we measured brain activity with magnetoencephalography (MEG) with
      an aim to characterize and classify single MEG trials during finger movements. We
      also examined whether averaging consecutive trials, or averaging signals from
      neighboring sensors, would improve classification accuracy. METHODS: MEG was
      recorded in five subjects during lifting the left, right or both index fingers.
      Trials were classified using features, defined by an expert, from averaged
      spectra and time-frequency representations. RESULTS: Classification accuracy of
      left vs. right finger movements was 80-94%. In the three-category classification
      (left, right, both), accuracy was 57-67%. Averaging three consecutive trials
      improved classification significantly in three subjects. Instead, spatial
      averaging across neighboring sensors decreased accuracy. CONCLUSIONS: The use of
      averaged signals to find appropriate features for single-trial classification
      proved useful for the two-class classification. The classification accuracy was
      comparable to that in previous EEG studies. SIGNIFICANCE: MEG provides another
      useful method to measure brain signals to be used in BCIs. Good performance was
      obtained when the classified signals were generated by two distinct sources in
      the left and right hemisphere. The present findings should be extended to multi
      task cases involving additional brain areas.

PMID- 16413828
TI  - CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency
      patients with impaired memory B-cell differentiation.
AB  - The recently proposed Piqueras classification of common variable immunodeficiency
      (CVID) patients is based on flow cytometric quantification of IgD class-switched
      and CD27 membrane-expressing mature blood B cells. But, many patients also have
      circulating T cells with immunophenotypic abnormalities, often associated with
      clinical complications, such as splenomegaly, autoimmune disease, lymphoid
      proliferation and/or granulomatosis. In 50 unselected CIVD patients, classified
      according to CD27 and IgD B-cell expression, we analyzed T-lymphocyte subsets
      according to their expression of HLA-DR and intracellular perforin and/or
      granzyme B in CD8+ T lymphocytes, CCR7 and CD45RA. CD3+DR+ T-lymphocyte
      percentages, predominantly CD8+DR+, were significantly higher in patients with
      clinical complications. MB0 classified patients, characterized by fewer CD27+ B
      cells, had higher percentages of CD8+DR+ T lymphocytes expressing perforin and/or
      granzyme with a differentiated effector (CCR7- and CD45RA+) phenotype. In
      contrast, MB2 patients (with normal CD27+ and IgD- B cells) were free of clinical
      complications and showed no signs of T-cell activation. MB1 patients (normal
      CD27+ numbers but fewer IgD- B cells) were either clinically normal or had
      complications. Combining the set of markers described herein might better define
      homogeneous groups of patients for etiological studies and clearly segregate
      patients with clinical complications.

PMID- 16413829
TI  - Antimicrobial peptides from the skin of the Tsushima brown frog Rana
      tsushimensis.
AB  - The Tsushima brown frog Rana tsushimensis Stejneger, 1907 exists in reproductive
      isolation on the island of Tsushima, Japan. Six peptides with antimicrobial
      activity were isolated in pure form from an extract of the skin of this species
      and their amino acid sequences identified them as members of the brevinin-1 (one
      peptide), brevinin-2 (one peptide) and temporin (four peptides) families. The C
      terminally alpha-amidated brevinin-1 peptide (FLGSIVGALASALPSLISKIRN.NH2) lacks
      the cyclic heptapeptide domain Cys18-(Xaa)4-Lys-Cys24 at the COOH-terminus of the
      molecule that characterizes other members of that family. A structurally similar
      brevinin-1 peptide, also lacking the cyclic domain, was previously isolated from
      the skin of the Ryukyu brown frog Rana okinavana, indicative of a close
      phylogenetic relationship between the species. Brevinin-2TSa
      (GIMSLFKGVLKTAGKHVAGSLVDQLKCKITGGC) showed broad-spectrum growth inhibitory
      activity against a range of Gram-negative and Gram-positive bacteria (including
      methicillin-resistant Staphylococcus aureus) (minimum inhibitory concentrations<
      or =25 microM) and relatively low hemolytic activity against human erythrocytes
      (LD50=100 microM). The peptide therefore represents a candidate for drug
      development.

PMID- 16413830
TI  - Tolerance and biomarkers as useful tools for assessing environmental quality in
      the Oued Souss estuary (Bay of Agadir, Morocco).
AB  - The aim of this study was to assess aquatic environmental quality of Oued Souss
      (Agadir, Morocco). This estuary has been subjected for a long time to large
      amounts of sewage discharges and industrial effluents. Since November 2002, no
      waste outlets have been discharged in this site due to their connection to a
      wastewater purification plant. Firstly, we have compared metal tolerance of the
      annelid polychaete (Nereis diversicolor) originating from Oued Souss and a
      relatively clean site (Oualidia, Morocco). Secondly, we have evaluated with a
      multi-marker approach (acetylcholinesterase [AChE], glutathione-S-transferases
      [GSTs], catalase, thiobarbituric acid reactive substances [TBARs]) responses of
      worms to the pollution gradient. Results have shown that worms from Oued Souss
      have acquired tolerance to copper and zinc due to a long-term sub-lethal metal
      exposure and this metal tolerance was maintained in spite of the end of
      wastewater discharges in this site. Higher catalase, GSTs and TBARs values have
      been observed in worms from Oued Souss sampled before implantation of wastewater
      treatment. The multi-marker approach confirms that these worms have been
      submitted to various contaminants. In contrast, high inhibition in AChE
      activities measured in worms from Oued Souss could be explained by the continuous
      agricultural influence of nearest areas. The level of contamination was probably
      maintained since biomarker values were generally higher in worms from Oued Souss
      when compared to Oualidia.

PMID- 16413831
TI  - Kinetics behaviors of Na,K-ATPase: comparison of solubilized and DPPC:DPPE
      liposome reconstituted enzyme.
AB  - We describe and compare the main kinetic characteristics of rabbit kidney Na,K
      ATPase incorporated inside-out in DPPC:DPPE-liposomes with the C(12)E(8)
      solubilized and purified form. In proteoliposomes, we observed that the ATP
      hydrolysis of the enzyme is favored and also its affinity for Na(+)-binding sites
      increases, keeping the negative cooperativity with two classes of hydrolysis
      sites: one of high affinity (K(0.5)=6 microM and 4 microM for reconstituted
      enzyme and purified form, respectively) and another of low affinity (K(0.5)=0.4
      mM and 1.4 mM for reconstituted enzyme and purified form, respectively). Our data
      showed a biphasic curve for ATP hydrolysis, suggesting the presence of
      (alphabeta)(2) oligomer in reconstituted Na,K-ATPase similar to the solubilized
      enzyme. The Mg(2+) concentration dependence in the proteoliposomes stimulated the
      Na,K-ATPase activity up to 476 U/mg with a K(0.5) value of 0.4 mM. The Na(+) ions
      also presented a single saturation curve with V(M)=551 U/mg and K(0.5)=0.2 mM
      with cooperative effects. The activity was also stimulated by K(+) ions through a
      single curve of saturation sites (K(0.5)=2.8 mM), with cooperative effects and
      V(M)=641 U/mg. The lipid microenvironment close to the proteic structure and the
      K(+) internal to the liposome has a key role in enzyme regulation, affecting its
      kinetic parameters while it can also modulate the enzyme's affinity for substrate
      and ions.

PMID- 16413832
TI  - Release of mitochondrial DNA fragments from brain mitochondria of irradiated
      mice.
AB  - Recently, we demonstrated that the release of mtDNA fragments from mitochondria
      occurs as a result of the opening of a non-specific pore in the inner
      mitochondrial membrane. Here, we show that irradiation of mice stimulates the
      appearance of mtDNA fragments in the cytosolic fractions of the brain. The
      fragments of mtDNA were found as early as 1h after irradiation, when no
      observable alteration of mitochondrial functioning occurred. The involvement of
      mitochondrial permeability transition in this process is discussed.

PMID- 16413833
TI  - An improved technique for repeated bronchoalveolar lavage and lung mechanics
      measurements in individual rats.
AB  - Lung function and bronchoalveolar lavage (BAL) fluid are commonly analyzed to
      assess the severity of lung disease in sacrificed animals. The input impedance of
      the respiratory system (Z(rs)) was measured and BAL fluid was collected in
      intubated, anesthetized, mechanically ventilated rats on three occasions 1 week
      apart. Measurements were performed in control animals (group C), while lung
      injury was induced in the other group (group LPS) by i.p. injection of
      lipopolysaccharide (LPS) before the second measurement. The airway resistance
      (R(aw)), tissue damping (G) and elastance (H) were determined from the Z(rs)
      spectra. The total cell counts (TC) from 0.3- to 0.4-ml BAL fluid were also
      determined. R(aw) exhibited no significant change in either group C (-6.7+/
      3.6[S.E.]%) or LPS (-0.9+/-3.7%). Reproducible G and H values were obtained in
      group C (2.5+/-5.3%, -7.0+/-4.4%), while G and H increased in group LPS (18.4+/
      6.5%, 14.9+/-13.8%, p<0.05). The changes in TC followed a similar pattern to
      those observed in G, with no change in group C (-7.9+/-30%), but with a marked
      increase in group LPS (580+/-456%, p<0.05). The method devised for repeated BAL
      measurements in another group of rats without intubation and muscle relaxant
      resulted in similar results in BAL profile. We conclude that longitudinal follow
      up of the airway and tissue mechanics and inflammatory cells in the BAL fluid are
      feasible in rats. The current method allows an early detection of lung injury,
      even in a relatively mild form.

PMID- 16413835
TI  - Deep diving mammals: Dive behavior and circulatory adjustments contribute to
      bends avoidance.
AB  - A mathematical model was created that predicted blood and tissue N(2) tension
      (P(N2)) during breath-hold diving. Measured muscle P(N2) from the bottlenose
      dolphin after diving repeatedly to 100 m (Tursiops truncatus [Ridgway and Howard,
      1979, Science, 4423, 1182-1183]) was compared with predictions from the model.
      Lung collapse was modelled as a 100% pulmonary shunt which yielded tissue P(N2)
      similar to those reported for the dolphin. On the other hand, predicted muscle
      P(N2) for an animal with a dive response, reducing cardiac output by 66% from
      surface values (20.5 to 6.8l x min(-1)), also agreed well with observed values in
      the absence of lung collapse. In fact, modelling indicated that both
      cardiovascular adjustments and dive behaviour are important in reducing N2 uptake
      during diving and enhancing safe transfer of tissue and blood N2 back to the lung
      immediately before coming to the surface. In particular, diving bradycardia
      during the descent and bottom phase together with a reduced ascent rate and
      increase in heart rate reduced mixed venous P(N2) upon return to the surface by
      as much as 45%. This has important implications as small reductions in inert gas
      load (approximately 5%) can substantially reduce decompression sickness (DCS)
      risk by as much as 50% (Fahlman et al., 2001, J. Appl. Physiol. 91, 2720-2729).

PMID- 16413834
TI  - Gene deletional strategies reveal novel physiological roles for myoglobin in
      striated muscle.
AB  - Myoglobin is an abundant hemoprotein that is expressed in cardiomyocytes and
      oxidative skeletal myofibers of vertebrates. Elegant studies using physiological,
      biochemical and spectroscopic analyses support a role for myoglobin in
      facilitated oxygen transport and as a reservoir for oxygen in muscle of diving
      and hypoxia-adapted animals. In contrast, the functional role of myoglobin in
      terrestrial animals that function at ambient oxygen levels is a subject of
      debate. This debate was further fueled by the observation that genetically
      engineered mice that lack myoglobin are viable and capable of withstanding the
      hemodynamic stress associated with reproduction. Analysis of the myoglobin mutant
      striated muscle reveals a spectrum of adaptive mechanisms that partially
      compensate for the absence of myoglobin and further supports an important
      function for this hemoprotein in the maintenance of contractile function during
      exercise under ambient and hypoxic conditions. Future studies utilizing
      transgenic and gene deletional strategies will further enhance our understanding
      of myoglobin function under normoxic and hypoxic conditions and will impact our
      understanding of exercise physiology.

PMID- 16413836
TI  - Determination of zolmitriptan in human plasma by liquid chromatography-tandem
      mass spectrometry method: application to a pharmacokinetic study.
AB  - A sensitive and selective liquid chromatography-tandem spectrometry method for
      the determination of zolmitriptan was developed and validated over the linearity
      range 0.05-30 ng/ml with 0.5 ml of plasma using diphenhydramine as the internal
      standard. Liquid-liquid extraction using a mixture of diethyl ether and
      dichloromethane was used to extract the drug and the internal standard from
      plasma. The mass spectrometer was operated under the selected reaction monitoring
      (SRM) mode using the atmospheric pressure chemical ionization (APCI) technique.
      The instrument parameters were optimized to obtain 3.0 min run time. The mobile
      phase consisted of acetonitrile-water-formic acid (70:30:0.5), at a flow rate of
      0.5 ml/min. In positive mode, zolmitriptan produced a protonated precursor ion at
      m/z 288 and a corresponding product ion at m/z 58. And internal standard produced
      a protonated precursor ion at m/z 256 and a corresponding product ion at m/z 167.
      The inter- and intra-day precision (%R.S.D.) were less than 8.5% and accuracy
      (%error) was less than -2.5%. The method had a lower limit of quantification of
      0.05 ng/ml for zolmitriptan, which offered increased sensitivity and selectivity
      of analysis, compared with existing methods. The method was successfully applied
      to a pharmacokinetic study of zolmitriptan after an oral administration of 5 mg
      zolmitriptan to 20 healthy volunteers.

PMID- 16413837
TI  - Structural changes accompanying human serum albumin's binding of fatty acids are
      concerted.
AB  - Long chain fatty acids (LCFAs), a major source of cellular energy, are
      solubilized and transported in the blood by binding to serum albumin. Changes in
      human serum albumin's (HSA's) UV absorption and characteristic reactivity with
      pyridoxal-5'-phosphate appear to reflect a concerted change in its structure upon
      binding five equivalents of myristate. Isothermal titrations with myristate and
      other LCFA anions are also consistent with the presence of five strong,
      interacting, binding sites. Although HSA is usually thought to have many
      independent LCFA anion binding sites, just five interacting sites appear to
      account for the changes in structure that accompany its binding of myristate.

PMID- 16413838
TI  - Mast cell density, neoplastic angiogenesis and their prognostic importance.

PMID- 16413839
TI  - Cochrane reviews in pregnancy: the role of perinatal randomized trials and
      systematic reviews in establishing evidence.
AB  - Evidence from randomized trials and systematic reviews provides the highest level
      of evidence from which to make clinical decisions. There are over 340 Cochrane
      reviews and protocols in pregnancy and childbirth; these provide the best single
      source of evidence for care of pregnant women and their babies, and highlight
      further research priorities. The challenges to health professionals are to ensure
      that the Cochrane reviews are prepared, kept up to date, and used in clinical
      care, and where relevant reliable evidence is not available to ensure that high
      quality randomized trials are promptly conducted.

PMID- 16413840
TI  - Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced
      osteoporosis in rats independent of its enhancement in intestinal calcium
      absorption.
AB  - AIM: Factorial design was used to test our hypothesis whether a group of
      flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its
      preventive effects on estrogen-deficiency-induced osteoporosis mainly through an
      enhancement in intestinal calcium absorption. MATERIALS AND METHODS: Forty-five
      12-month-old female Wistar rats were used and randomly assigned into sham
      operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX
      group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX
      with FE and CS (FE + CS group). Daily oral administration of FE (10 mg/kg/day)
      and/or CS (56 mg/kg/day) started on day 4 after OVX for 12 weeks. Before
      sacrificing the animals, urine and serum samples were collected for assaying
      indicators related to intestinal calcium absorption, regulator for calcium
      homeostasis, and markers of bone turnover. The left proximal femur was dissected
      for evaluation of the primary end-point (failure force), the second end-points
      (pQCT-quantified densitometry, geometry, and micro-CT-quantified 3-D trabecula
      micro-architecture), and pQCT-defined cross-sectional envelope. RESULTS: FE was
      found to be able to prevent OVX-induced reduction in failure force as well as the
      above second end-points, without resulting in an increased uterus weight. CS had
      no preventive effect on OVX-induced reduction in failure force. Two-way factorial
      interaction analysis between FE and CS showed that the un-enhanced suppression of
      parathyroid hormone for calcium homeostasis did not provide link between the
      enhanced intestinal calcium absorption and the enhanced inhibition of bone
      resorption in the present study. Furthermore, the discrepancies between the
      enhanced intestinal calcium absorption and the un-enhanced end-point measures as
      well as anabolic effect were also revealed by the interaction analysis.
      CONCLUSION: The present study suggested that FE inhibited bone resorption,
      stimulated bone formation, and accordingly prevented osteoporosis without
      hyperplastic effect on uterus in the OVX rat model, which was however independent
      of an enhancement in intestinal calcium absorption.

PMID- 16413841
TI  - The World Health Organization's global guidance for family planning: an
      achievement to celebrate.

PMID- 16413842
TI  - Effective use of hormonal contraceptives: Part I: Combined oral contraceptive
      pills.
AB  - This systematic review examines evidence regarding when during the menstrual
      cycle a woman can initiate combined oral contraceptive (COC) use and what can be
      done if a woman misses COCs. We searched the MEDLINE and EMBASE databases for
      articles published from 1966 to March 2005 related to COC initiation and to the
      effects of late or missed COCs. We identified 11 studies related to COC
      initiation and 25 studies related to the effects of missed pills. Evidence from
      these studies suggested that taking hormonally active pills for 7 consecutive
      days prevents normal ovulation and that initiating COCs through Day 5 of the
      menstrual cycle suppresses follicular activity. Studies on the effects of missed
      COCs generally showed that the risk of ovulation is greatest when the pill-free
      interval lasts >7 days. Limitations of this body of evidence include small sample
      sizes that may not reflect variation in larger populations, lack of a standard
      measurement of ovulation and difficulty in discerning how ovulation resulting
      from late or missed COCs corresponds to the risk of conception.

PMID- 16413843
TI  - Effective use of hormonal contraceptives: Part II: Combined hormonal injectables,
      progestogen-only injectables and contraceptive implants.
AB  - Our objective in this systematic review was to evaluate evidence regarding
      controversial issues in the clinical management of women using injectable and
      implantable contraceptives. We searched MEDLINE and EMBASE for reports of primary
      research, published from 1966 through April 2005 in peer-reviewed journals,
      related to the initiation of combined or progestogen-only injectables and
      contraceptive implants, the effects of late contraceptive injections or the
      duration of levonorgestrel implant effectiveness. Results of the studies we
      reviewed showed that initiating injectable and implantable contraceptives through
      day 7 of the menstrual cycle suppresses follicular activity. Time to ovulation
      after study participants discontinued using injectables varied widely: from 4 to
      8 weeks after the last administration of combined injectables, from 15 to 49
      weeks after the last injection of depot medroxyprogesterone acetate and from 5 to
      19 weeks after the last injection of norethisterone enanthate. Norplant implants
      left in place for up to seven completed years remained effective among women who
      weighed <70 kg at the time of implant insertion, but their effectiveness
      decreased among women weighing >or=70 kg.

PMID- 16413844
TI  - Medical eligibility criteria for new contraceptive methods: combined hormonal
      patch, combined hormonal vaginal ring and the etonogestrel implant.
AB  - To review evidence on the combined hormonal patch, combined hormonal vaginal ring
      and the etonogestrel implant, with a focus on safety and effectiveness of use
      among women with special health conditions, we searched MEDLINE, Pre-MEDLINE and
      the Cochrane Library for reports published from 1980 through March 2005. Articles
      eligible for review included 11 on the hormonal patch, nine on the hormonal ring,
      and 11 on the etonogestrel implant. Limited evidence suggests patch efficacy is
      lower among women>90 kg. No evidence was identified for vaginal ring use among
      women with medical conditions. A single small study found that etonogestrel
      implants had no adverse effects on bone mineral density among women 18-40 years
      old. Limited evidence also suggests no adverse effects of the etonogestrel
      implant on lactation parameters or infant development among users enrolled 28 to
      56 days postpartum and followed for 4 months.

PMID- 16413845
TI  - Does insertion and use of an intrauterine device increase the risk of pelvic
      inflammatory disease among women with sexually transmitted infection? A
      systematic review.
AB  - Concerns exist as to whether the insertion of copper and levonorgestrel-releasing
      intrauterine devices (IUDs) increases the risk of pelvic inflammatory disease
      (PID) among women with sexually transmitted infection (STI). We searched the
      MEDLINE database for all articles published between January 1966 and March 2005
      that included evidence relevant to IUDs and STIs and PID. None of the studies
      that examined women with STIs compared the risk of PID between those with
      insertion or use of an IUD and those who had not received an IUD. We reviewed
      indirect evidence from six prospective studies that examined women with insertion
      of a copper IUD and compared risk of PID between those with STIs at the time of
      insertion with those with no STIs. These studies suggested that women with
      chlamydial infection or gonorrhea at the time of IUD insertion were at an
      increased risk of PID relative to women without infection. The absolute risk of
      PID was low for both groups (0-5% for those with STIs and 0-2% for those
      without).

PMID- 16413846
TI  - Hormonal contraceptive use and risk of sexually transmitted infections: a
      systematic review.
AB  - Previous research has suggested that hormonal contraceptive users, compared with
      nonusers, may be at increased risk for acquiring sexually transmitted infections
      (STIs). We searched the MEDLINE and EMBASE databases for all articles from
      January 1966 through February 2005 for evidence relevant to all hormonal
      contraceptives and STIs (including cervical chlamydial and gonococcal infection,
      human papillomavirus, trichomoniasis, herpes and syphilis). We used standard
      abstract forms and grading systems to summarize and assess the quality of 83
      identified studies. Studies of combined oral contraceptive and depot
      medroxyprogesterone use generally reported positive associations with cervical
      chlamydial infection, although not all associations were statistically
      significant. For other STIs, the findings suggested no association between
      hormonal contraceptive use and STI acquisition, or the results were too limited
      to draw any conclusions. Evidence was generally limited in both amount and
      quality, including inadequate adjustment for confounding, lack of appropriate
      control groups and small sample sizes. The observed positive associations may be
      due to a true association or to bias, such as differential exposure to STIs by
      contraceptive use or increased likelihood of STI detection among hormonal
      contraceptive users.

PMID- 16413847
TI  - Does use of hormonal contraceptives among women with thrombogenic mutations
      increase their risk of venous thromboembolism? A systematic review.
AB  - Because use of combined oral contraceptives (COCs) confers some risk of venous
      thromboembolism (VTE), there is concern that this effect may be greater among
      women with thrombogenic mutations. We searched the MEDLINE and EMBASE databases
      for all articles published from January 1966 through September 2004 for evidence
      relevant to hormonal contraception and thrombogenic mutations. Of 301 articles
      identified by the search strategy, 16 evaluated COCs, and no studies were found
      for other hormonal methods. We used standard abstract forms and grading systems
      to summarize and assess the quality of the evidence. A total of 10 studies
      together provided "good" evidence of a greater risk of VTE (risk ratios of 1.3
      25.1) and cerebral vein or cerebral sinus thrombosis among COC users with factor
      V Leiden mutation when compared with nonusers who have the mutation. The evidence
      for prothrombin and other thrombogenic mutations was not as strong as for factor
      V Leiden mutation. It is unclear whether the type of COC or duration of use
      modifies the risk of VTE among women with thrombogenic mutations.

PMID- 16413848
TI  - Combined oral contraceptive use among women with hypertension: a systematic
      review.
AB  - Women with hypertension are at increased risk for cardiovascular events. Combined
      oral contraceptive (COC) use, even among low-dose users, has been associated with
      a small excess risk for cardiovascular events among healthy women. In this
      systematic review, we examined cardiovascular risks among COC users with
      hypertension. After searching MEDLINE for all articles published from 1966
      through February 2005 relevant to COC use, hypertension and cardiovascular
      disease, we identified 25 articles for this review. Overall, these studies showed
      that hypertensive COC users were at higher risk for stroke and acute myocardial
      infarction (AMI) than hypertensive non-COC users, but that they were not at
      higher risk for venous thromboembolism (VTE). Women who did not have their blood
      pressure measured before initiating COC use were at higher risk for ischemic
      stroke and AMI, but not for hemorrhagic stroke or VTE, than COC users who did not
      have their blood pressure measured.

PMID- 16413849
TI  - Use of combined oral contraceptives among women with migraine and nonmigrainous
      headaches: a systematic review.
AB  - This systematic review examines evidence evaluating whether women with headaches
      who use combined oral contraceptives (COCs) have a greater risk of stroke than
      women with headaches who do not use COCs. We searched MEDLINE for articles
      published from 1966 through March 2005 relevant to headaches and COC use as risk
      factors for stroke. Of the 79 articles identified, nine met our selection
      criteria (eight reports of six observational studies plus one meta-analysis). All
      studies reported specifically on migraine headaches. Evidence from six case
      control studies suggested that COC users with a history of migraine were two to
      four times as likely to have an ischemic stroke as nonusers with a history of
      migraine. The odds ratios for ischemic stroke ranged from 6 to almost 14 for COC
      users with migraine compared with nonusers without migraine. The three studies
      that provided evidence on hemorrhagic stroke reported low or no risk associated
      with migraine or with COC use.

PMID- 16413851
TI  - Regret following female sterilization at a young age: a systematic review.
AB  - Women who undergo sterilization may later regret this decision. This systematic
      review examines whether age at sterilization is associated with poststerilization
      regret. Using MEDLINE and EMBASE, we identified 19 articles that examined
      associations between women's age at sterilization and later regret, requests for
      sterilization reversal and undergoing sterilization reversal or requesting in
      vitro fertilization (IVF) procedures. Study results showed that the younger women
      were at the time of sterilization, the more likely they were to report regretting
      that decision. Women undergoing sterilization at the age 30 years or younger were
      about twice as likely as those over 30 to express regret. They were also from 3.5
      to 18 times as likely to request information about reversing the procedure and
      about 8 times as likely to actually undergo reversal or an evaluation for IVF.
      Results of studies that examined risk by continuous age showed a consistent
      inverse relationship between women's age at sterilization and their likelihood of
      regretting having had the procedure.

PMID- 16413852
TI  - Mandating parental involvement in adolescents' abortion: implications of a short
      sighted policy.

PMID- 16413850
TI  - Progestogen-only contraceptive use among women with sickle cell anemia: a
      systematic review.
AB  - The use of progestogen-only contraceptives among women with sickle cell anemia
      has generated concerns about possible hematological and other clinical
      complications. Based on the literature, we assessed whether use of progestogen
      only contraceptives is associated with adverse health effects among women with
      sickle cell anemia. We searched the MEDLINE database for articles published in
      peer-reviewed journals between 1966 and September 2004 that were relevant to
      sickle cell anemia and use of progestogen-only contraceptives. Of the 70 articles
      identified through the search, 8 met the criteria for this review. These studies
      did not identify any adverse events or clinically or statistically significant
      adverse changes in hematological or biochemical parameters associated with the
      use of progestogen-only contraceptive methods. Six studies suggested that users
      experienced a decrease in clinical symptoms and less frequent and severe painful
      crises compared with nonusers. Although data are limited, these studies suggest
      that progestogen-only contraceptives are safe for women with sickle cell anemia.

PMID- 16413853
TI  - Choice policies must focus on reducing health inequalities.

PMID- 16413854
TI  - A universal code of ethics falls badly short.

PMID- 16413855
TI  - A sensible 10-year plan for mental health.

PMID- 16413856
TI  - Stem-cell therapy after acute myocardial infarction: the focus should be on those
      at risk.

PMID- 16413857
TI  - Thin-layer cervical cytology: a new meta-analysis.

PMID- 16413858
TI  - Iron and folic acid supplementation and malaria risk.

PMID- 16413859
TI  - Endogenous opioids and hot flushes still hypothetical.

PMID- 16413860
TI  - Interleukin-2 therapy and CD4+ T cells in HIV-1 infection.

PMID- 16413861
TI  - Long-term effects of sarin.

PMID- 16413862
TI  - Big pharma and the UK Government.

PMID- 16413863
TI  - Hypochondria.

PMID- 16413865
TI  - Trastuzumab for early breast cancer.

PMID- 16413866
TI  - Trastuzumab for early breast cancer.

PMID- 16413867
TI  - Trastuzumab for early breast cancer.

PMID- 16413869
TI  - Surgical resection in metastatic spinal cord compression.

PMID- 16413870
TI  - Surgical resection in metastatic spinal cord compression.

PMID- 16413873
TI  - Artesunate versus quinine for severe falciparum malaria.

PMID- 16413871
TI  - Artesunate versus quinine for severe falciparum malaria.

PMID- 16413874
TI  - Sandflies and leishmaniasis.

PMID- 16413875
TI  - Autologous bone marrow-derived stem-cell transfer in patients with ST-segment
      elevation myocardial infarction: double-blind, randomised controlled trial.
AB  - BACKGROUND: The benefit of reperfusion therapies for ST-elevation acute
      myocardial infarction (STEMI) is limited by post-infarction left-ventricular (LV)
      dysfunction. Our aim was to investigate the effect of autologous bone marrow
      derived stem cell (BMSC) transfer in the infarct-related artery on LV function
      and structure. METHODS: We did a randomised, double-blind, placebo-controlled
      study in 67 patients from whom we harvested bone marrow 1 day after successful
      percutaneous coronary intervention for STEMI. We assigned patients optimum
      medical treatment and infusion of placebo (n=34) or BMSC (n=33). Our primary
      endpoint was the increase in LV ejection fraction and our secondary endpoints
      were change in infarct size and regional LV function at 4 months' follow-up, all
      assessed by MRI. We assessed changes in myocardial perfusion and oxidative
      metabolism with serial 1-[11C]acetate PET. Analyses were per protocol. This study
      is registered with , number NCT00264316. FINDINGS: Mean global LV ejection
      fraction 4 days after percutaneous coronary intervention was 46.9% (SD 8.2) in
      controls and 48.5% (7.2) in BMSC patients, and increased after 4 months to 49.1%
      (10.7) and 51.8% (8.8; OR for treatment effect 1.036, 95% CI 0.961-1.118,
      p=0.36). Compared with placebo infusion, BMSC transfer was associated with a
      significant reduction in myocardial infarct size (BMSC treatment effect 28%,
      p=0.036) and a better recovery of regional systolic function. Myocardial
      perfusion and metabolism increased similarly in both groups. We noted no
      complications associated with BMSC transfer and all but one patient in the BMSC
      group completed the 4 months' follow-up. INTERPRETATION: Intracoronary transfer
      of autologous bone marrow cells within 24 h of optimum reperfusion therapy does
      not augment recovery of global LV function after myocardial infarction, but could
      favourably affect infarct remodelling.

PMID- 16413876
TI  - Effect of study design and quality on unsatisfactory rates, cytology
      classifications, and accuracy in liquid-based versus conventional cervical
      cytology: a systematic review.
AB  - BACKGROUND: Liquid-based cytology is reported to increase the sensitivity of
      cervical cytology and the proportion of slides that are satisfactory for
      assessment, in comparison with conventional cytology. Although some countries
      have changed to liquid-based cytology for cervical screening, controversy
      remains. We reviewed the published work to assess the performance of liquid-based
      cytology relative to conventional cytology in primary studies assessed to be of
      low, medium, or high methodological quality. METHODS: 56 primary studies were
      reviewed and assessed with strict methodological criteria. Liquid-based cytology
      and conventional cytology were compared in terms of the percentage of slides
      classified as unsatisfactory, the percentage of slides classified in each
      cytology category, and the accuracy of detection of high-grade disease. Data were
      examined for studies overall and in strata to examine the effect of study quality
      on results. FINDINGS: The median difference in the percentage of unsatisfactory
      slides between liquid-based cytology and conventional cytology was 0.17%. Only
      one small study was a randomised controlled trial. The classification of high
      grade squamous epithelial lesion varied according to study quality (p=0.04), with
      conventional cytology classifying more slides in this category than did liquid
      based cytology in high-quality studies (n=3) only. In medium-quality (n=30) and
      high-quality studies, liquid-based cytology classified more slides as atypical
      squamous cells of unknown significance than did conventional cytology when
      compared with low-quality studies (n=17; p=0.05). Only four studies provided
      sufficient verified data to allow estimation of sensitivity and specificity and
      comparison of test accuracy. INTERPRETATION: We saw no evidence that liquid-based
      cytology reduced the proportion of unsatisfactory slides, or detected more high
      grade lesions in high-quality studies, than conventional cytology. This review
      does not lend support to claims of better performance by liquid-based cytology.
      Large randomised controlled trials are needed.

PMID- 16413877
TI  - Effects of routine prophylactic supplementation with iron and folic acid on
      admission to hospital and mortality in preschool children in a high malaria
      transmission setting: community-based, randomised, placebo-controlled trial.
AB  - BACKGROUND: Anaemia caused by iron deficiency is common in children younger than
      age 5 years in eastern Africa. However, there is concern that universal
      supplementation of children with iron and folic acid in areas of high malaria
      transmission might be harmful. METHODS: We did a randomised, placebo-controlled
      trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned
      children to daily oral supplementation with: iron (12.5 mg) and folic acid (50
      mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children
      aged 1-11 months received half the dose. Our primary endpoints were all-cause
      mortality and admission to hospital. Analyses were by intention to treat. This
      study is registered as an International Standard Randomised Controlled Trial,
      number ISRCTN59549825. FINDINGS: The iron and folic acid-containing groups of the
      trial were stopped early on Aug 19, 2003, on the recommendation of the data and
      safety monitoring board. To this date, 24 076 children contributed a follow-up of
      25,524 child-years. Those who received iron and folic acid with or without zinc
      were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital
      for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to
      hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups.
      INTERPRETATION: Routine supplementation with iron and folic acid in preschool
      children in a population with high rates of malaria can result in an increased
      risk of severe illness and death. In the presence of an active programme to
      detect and treat malaria and other infections, iron-deficient and anaemic
      children can benefit from supplementation. However, supplementation of those who
      are not iron deficient might be harmful. As such, current guidelines for
      universal supplementation with iron and folic acid should be revised.

PMID- 16413879
TI  - Recent developments and current controversies in depression.
AB  - In this review of the last 5 years' developments in research into depression we
      focus on recent advances and current controversies. We cover epidemiology and
      basic science as well as the treatment of depression in adults in all its forms.
      Depression in , as well as in has been covered in recent Seminars in The Lancet.
      Depression in adulthood remains a very common and under-treated condition,
      resulting in a high degree of disability. Increasingly detailed knowledge about
      impairment of information processing in depression is being supplemented by
      quantitative studies of the brain processes underlying these impairments. Most
      patients improve with present treatments. The mechanisms of action of
      antidepressants are not fully understood; the hypothesis that reversing
      hippocampal cell loss in depression may be their active principle is a
      fascinating new development. Moral panic about the claim that antidepressant
      serotonin reuptake inhibitors cause patients to commit suicide and become
      addicted to their medication may have disconcerted the public and members of the
      medical profession. We will try to describe the considerable effort that has gone
      into collecting evidence to enlighten this debate.

PMID- 16413878
TI  - Effect of routine prophylactic supplementation with iron and folic acid on
      preschool child mortality in southern Nepal: community-based, cluster-randomised,
      placebo-controlled trial.
AB  - INTRODUCTION: Iron deficiency is widespread in the developing world and is
      especially common in young children who live on the Indian subcontinent.
      Supplementation with iron and folic acid alleviates severe anaemia and enhances
      neurodevelopment in deficient populations, but little is known about the risks of
      mortality and morbidity associated with supplementation. METHODS: We did a
      community-based, cluster-randomised, double-masked, placebo-controlled, 2x2
      factorial trial in children aged 1-36 months and residing in southern Nepal. We
      randomly assigned children daily oral supplementation to age 36 months with: iron
      (12.5 mg) and folic acid (50 microg; n=8337), zinc alone (10 mg), iron, folic
      acid, and zinc (n=9230), or placebo (n=8683); children aged 1-11 months received
      half the dose. Our primary outcome measure was all-cause mortality, and our
      secondary outcome measures included cause-specific mortality and incidence and
      severity of diarrhoea, dysentery, and acute respiratory illness. Analyses were by
      intention to treat. This study is registered at , number NCT00109551. FINDINGS:
      The iron and folic acid-containing groups of the study were stopped early in
      November, 2003, on the recommendation of the data and safety monitoring board;
      mortality in these groups did not differ from placebo and there was low power to
      detect positive or negative effects by the time enrollment was completed. We
      continued to enroll children to the placebo and zinc alone groups. 25,490
      children participated and analyses are based on 29,097.3 person-years of follow
      up. There was no difference in mortality between the groups who took iron and
      folic acid without or with zinc when compared with placebo (HR 1.03, 95% CI 0.78
      1.37, and 1.00, 0.74-1.34, respectively). There were no significant differences
      in the attack rates for diarrhoea, dysentery, or respiratory infections between
      groups, although all the relative risks except one indicated modest, non
      significant protective effects. INTERPRETATION: Daily supplementation of young
      children in southern Nepal with iron and folic acid with or without zinc has no
      effect on their risk of death, but might protect against diarrhoea, dysentery,
      and acute respiratory illness.

PMID- 16413880
TI  - Controversies in hypertension.
AB  - Hypertension remains the most common risk factor for cardiovascular morbidity and
      mortality. Its incidence is rising in both ageing and obese populations, but its
      control remains inadequate worldwide. We address several persisting controversies
      that may interfere with appropriate management of hypertension. They include: the
      reasons behind the increasing incidence of hypertension and the possible ways to
      slow the process, especially by lifestyle changes; the need for overall
      cardiovascular risk assessment; the major issues in the decision to institute
      drug therapy and the choice of drugs; and the importance of screening for various
      identifiable causes. We provide the background for these controversies, followed
      by some opinions on how to guide practitioners to offer more effective management
      of hypertension.

PMID- 16413881
TI  - Surgical professionalism in the 21st century.

PMID- 16413882
TI  - Varicella zoster virus cerebellitis in a 66-year-old patient without herpes
      zoster.

PMID- 16413883
TI  - The high cost of infrequent events.

PMID- 16413884
TI  - Influence of estrogen on brain activation during stimulation with painful heat.
AB  - PURPOSE: Several studies have shown that women express higher pain sensitivity
      during periods of low estrogen than during periods of high estrogen. The aim of
      this study was to show whether the difference in pain sensitivity could be
      visualized as a function of brain activity by means of functional magnetic
      resonance imaging (fMRI). METHODS: Nine healthy, pain-free women (mean age, 26.2
      +/- 6.9 years) with a natural, regular menstrual cycle participated in the study.
      Whole-brain fMRI data were acquired during a period of high and during a period
      of low estrogen at 1.5 T using echo-planar imaging with near-isotropic spatial
      resolution and a temporal resolution of 4 seconds. Heat pain thresholds were
      obtained before the scans, and pain ratings were obtained before and after each
      scan. Blood samples were taken after each scan to verify the appropriate level of
      estrogen. RESULTS: The heat pain thresholds during the low (46.4 degrees +/- 3.5
      degrees C) and high (46.4 degrees +/- 3.8 degrees C) estrogen conditions were not
      significantly different. The pain ratings before (4.6 +/- 2.2 low versus 3.6 +/-
      2.1 high) and during the scans (4.4 +/- 2.4 low versus 4.7 +/- 2.3 high) also did
      not differ between the 2 conditions. Generally, similar patterns of activation
      were observed for both estrogen conditions. However, significant differences were
      found in the magnitude of activation of the anterior part of the anterior
      cingulate (BA 24/32), the cerebellum, and the precuneus. Furthermore, activations
      in the anterior part of the anterior cingulate, left cerebellum, and precuneus
      were unique to the low-estrogen phase. These regions have been linked with
      attention to or anticipation of pain. CONCLUSIONS: The results of this study
      suggest that the affective component of pain may be enhanced during the low
      estrogen phase of the menstrual cycle in healthy women.

PMID- 16413885
TI  - Mandibular remodeling after bilateral sagittal split osteotomy for prognathism of
      the mandible.
AB  - PURPOSE: To describe the postoperative remodeling changes in the mandible after
      bilateral sagittal split osteotomy to correct mandibular prognathism. PATIENTS
      AND METHODS: Twenty patients who underwent bilateral sagittal split osteotomy for
      the correction of mandibular prognathism were studied for postoperative
      remodeling changes within the mandible. The 6-week, 1-year, and long-term
      postoperative cephalometric mandibular tracings of 12 patients were superimposed
      using the fixation wires as the stable reference points to demonstrate the
      specific locations of the intrabony remodeling. RESULTS: There was a general
      direction of remodeling at the condylion and gonion anteriorly and superiorly,
      while the B point and pogonion did not show much change in remodeling. At the
      condylion, 60% and 40% of the cases showed significant horizontal and vertical
      remodeling, respectively. At the gonion, 50% and 55% of the cases showed
      significant horizontal and vertical remodeling, respectively. No correlation was
      found between the remodeling changes at condylion and gonion and the surgical
      movement or relapse at B point and pogonion. There was a significant correlation
      between the observed horizontal relapse at gonion and the horizontal remodeling
      changes at this point showing that the postoperative displacement of this point
      is a result of both positional translocation and remodeling changes. CONCLUSION:
      The results of this study show that there are intrabony remodeling changes that
      occur in the mandible after sagittal split osteotomy and that these continue for
      a long period of time in some patients. This remodeling occurred more in the
      condylar and gonial areas, while the chin remained relatively stable.

PMID- 16413886
TI  - A 10-year comparative study of the incidence of third molar removal in the aging
      population.
AB  - PURPOSE: The study goal was to evaluate the incidence of patients older than 40
      years who required third molar removal. PATIENTS AND METHODS: Two prospective 5
      year studies were compared over a 10-year period of 1992 to 1997 and 1997 to
      2002. The study was initiated to evaluate how the large increase in the older
      population with longer life expectancies is reflected in the third molar
      population. RESULTS: In 1997, 10.5% of patients requiring third molar surgery
      were 40 years or older. In 2002, 17.3% of patients were 40 years or older.
      CONCLUSIONS: It is well known that patients 40 years and older have increased
      risk in removal of third molars. It is concluded that 1 patient in 5 in the high
      risk category is in a very high risk category. The risk to patients and to the
      profession can be dramatically reduced by considering early removal of abnormal
      third molars.

PMID- 16413887
TI  - Analysis of muscle hardness in patients with masticatory myofascial pain.
AB  - PURPOSE: The aim of the present study was to access any changes in the muscle
      hardness of the masseter muscle between normal subjects and patients with
      myofascial pain during brief sustained isometric contractions at various bite
      force levels, and to compare muscle hardness, especially in terms of the recovery
      phase, after a clenching task. MATERIALS AND METHODS: Ten patients with
      masticatory myofascial pain and 10 age- and weight-matched normal healthy
      controls participated in this study. First, the hardness of the right masseter
      muscle was measured at the bite force of 0, 3, 6, and 9 kgf with a hand-held
      hardness meter. Then, the subjects were requested to exert a 9 kgf-clenching task
      for 30 seconds. The muscle hardness was again measured at 5, 30, and 120 seconds
      after the task, and the data obtained were compared with the muscle hardness
      before the clenching task. RESULTS: The results showed that there was no
      significant difference between the patients and the normal controls, while the
      muscle hardness increased with contraction in all subjects. The present findings
      also showed that the patients had a delayed return to baseline after the
      clenching task compared with the normal subjects, although an immediate increase
      after the clenching task was seen in all subjects. CONCLUSION: The results
      indicated that patients with masticatory myofascial pain have different muscle
      properties in the recovery phase after contraction, probably because of a slower
      intramuscular reperfusion.

PMID- 16413888
TI  - Effects of low-intensity pulsed ultrasound on healing of mandibular fractures: an
      experimental study in rabbits.
AB  - PURPOSE: Pulsed ultrasonic waves have been shown to accelerate fracture healing
      of the long bones. The aim of this study was to evaluate the effects of low
      intensity pulsed ultrasound (LIPU) on healing of mandibular fractures. MATERIALS
      AND METHODS: Thirty skeletally mature male New Zealand rabbits were used. Animals
      underwent unilateral mandibular osteotomy. The bone segments were repositioned
      and fixed with miniplates and miniscrews. Half of the animals received daily
      ultrasound treatment, 20 min/day, for 20 days. Ultrasound signals consisted of a
      1.5-MHz pressure wave administered in pulses of 200 microsec with an average
      temporal and spatial intensity of 30 mW/cm2. Animals in the control group
      received sham application. All of the animals were killed on postoperative day
      22. Three-point bending test, digital radiodensitometric analysis, and histologic
      and histomorphometric examinations were performed on the harvested hemimandibles.
      The data were statistically analyzed. RESULTS: Biomechanical tests revealed
      significant improvement in the mechanical properties of the healing bone in the
      LIPU-treated group. This was supported by histologic and radiologic findings.
      CONCLUSIONS: Results of this study suggest that LIPU improves the bone healing of
      mandibular fractures in rabbits.

PMID- 16413889
TI  - Progression of periodontal disease in the second/third molar region in subjects
      with asymptomatic third molars.
AB  - PURPOSE: To assess the change in periodontal status over time by periodontal
      probing depth (PD) in the third molar region. SUBJECTS AND METHODS: The data for
      these analyses are part of a study of subjects enrolled with 4 asymptomatic third
      molars with adjacent second molars in an institutional review board-approved
      longitudinal trial. Full mouth periodontal probing was conducted to determine
      periodontal status at baseline and follow-up. Panoramic radiographs were analyzed
      for angulation and degree of eruption of third molars. Subjects were categorized
      as those who exhibited at least a 2 mm change in periodontal PD between baseline
      and follow-up in the third molar region, the distal of a second molar or around a
      third molar, and those who did not exhibit a 2 mm or greater change. Subjects
      with and without changes in PD were compared with Cochran-Mantel-Haenzsel
      statistics. Level of significance was set at 0.05. RESULTS: Data from 254
      subjects with at least 2 annual follow-up visits were available for analysis.
      Mean age at baseline was 27.5 years. Median follow-up from baseline to the second
      follow-up visit was 2.2 years (interquartile range 2.0, 2.6). At enrollment, 59%
      of the subjects had at least 1 PD > or =4 mm in the third molar region, one
      quarter had a PD > or =5 mm. Twenty-four percent of the subjects had at least 1
      tooth that had an increased PD > or =2 mm in the third molar region at follow-up.
      If subjects had at least 1 PD > or =4 mm at baseline, 38% had at least 1 PD
      deepen by 2 mm or more at follow-up. Only 3% of those who had all teeth with a PD
      of less than 4 mm at baseline exhibited a change of > or =2 mm (P < .001).
      CONCLUSION: Increased periodontal PDs > or =2 mm were often found in the third
      molar region for asymptomatic subjects with at least 1 PD > or =4 mm at
      enrollment, clinical measures that indicated increased periodontal pathology, and
      a deteriorating periodontal condition.

PMID- 16413890
TI  - The accuracy of cephalometric tracing superimposition.
AB  - PURPOSE: The purpose of this study was to compare the accuracy of 4 methods for
      cephalometric tracing superimposition. They are the FH@Porion method, S-N@Sella
      method, least-squared averaged 5 landmarks (LS-5) method, and manual geometric
      method. MATERIALS AND METHODS: Eight lateral cephalometric radiographs were used.
      Cephalometric tracing was performed by 2 examiners. One had extensive experience
      in landmark digitization while the other had minimal experience. The radiographs
      were scanned and the reference landmarks ANS, Point A, Point B, and Pogonion were
      digitized, creating 8 master tracings. Then 6 digital copies of each master
      tracing were made, 3 for each examiner. Subsequently, the examiners were asked to
      digitize and trace predetermined cranial base landmarks and structures. Tracings
      occurred at 1-month intervals. As a result, 3 separate tracings of each set were
      obtained from each examiner. The tracings of each set were superimposed using 4
      different methods in the CASSOS software (SoftEnable Technology Ltd, Hong Kong
      SAR, China). For each method of superimposition, the coordinates of ANS, Point A,
      Point B, and Pogonion were recorded. Their means and variances were calculated.
      The variance represents the variability of the superimposition method. A general
      linear model for repeated measures was computed to test whether there were
      statistically significant differences among the 4 superimposition methods, 2
      examiners, 4 reference landmarks, and 2 directions. Because the distribution of
      the variances was skewed, they were transformed to log variances. Finally, the
      errors of the superimposition in millimeters for each given examiner,
      superimposition method, reference landmark, and direction (X, Y) were calculated.
      RESULTS: There was a statistically significant difference in measurement
      variability among the 4 superimposition methods (P < .001). For both examiners,
      the variability of the different superimposition methods from the highest to the
      lowest was: Frankfort Plane registered at Porion method, Sella-Nasion registered
      at Sella method, least-square averaged 5 landmarks method, and the manual
      geometric method. In addition, there was a statistically significant difference
      in the magnitude of superimposition errors between the 2 examiners (P < .001).
      The experienced examiner was consistently more precise than the inexperienced
      examiner across all methods. Moreover, there was a statistically significant
      difference among 4 reference landmarks (P < .001). For both examiners, the
      recorded variability of each given reference landmark from the lowest to the
      highest was: ANS, Point A, Point B, and Pogonion. Furthermore, the variability
      differences between horizontal and vertical directions did not reach a
      conventional level of significance (P = .123). Finally, the recorded errors in
      millimeters for each superimposition method were summarized. A smaller error in
      millimeters represented a higher accuracy in superimposition. The error of using
      manual geometric or LS-5 methods for both examiners was less than 0.50 mm, while
      the error of using the other 2 methods was up to 0.99 mm for the experienced
      examiner and 2.88 mm for the inexperienced examiner. CONCLUSION: The error of
      both manual and LS-5 methods was within 0.5 mm. The LS-5 method had its advantage
      because it could be automated by the computer.

PMID- 16413891
TI  - Management of laryngo-tracheal injuries associated with craniomaxillofacial
      trauma.
AB  - PURPOSE: Laryngeal fractures can occur in association with maxillofacial injuries
      and may lead to life-threatening airway obstruction. Because of a low incidence
      and a paucity of peer-reviewed information, there is no universally accepted
      treatment protocol and few clinicians have extensive experience with complex
      laryngo-tracheal trauma. The purpose of this retrospective analysis is to
      validate a treatment protocol for the management of laryngo-tracheal injuries
      occurring in severely injured patients by assessing the outcome of a consecutive
      series of patients who were treated by the same surgeons over a 12-year period.
      PATIENTS AND METHODS: All patients with laryngeal fractures admitted to the
      trauma service at Legacy Emanuel Hospital and Health Center (LEHHC; Portland, OR)
      from 1992 to 2004 were managed by the same surgeons, using a standard protocol
      based on the stability of the airway, and were retrospectively identified using
      the LEHHC Trauma Registry. Using information from the Trauma Registry and
      individual physician chart notes, a database was created for the purpose of
      assessing outcome. The following data were collected: age, gender, mechanism of
      injury, number of associated injuries and the Injury Severity Score, Glasgow Coma
      Scale on admission, initial hematocrit, airway management techniques, length of
      hospital stay, LEHHC laryngeal injury classification, treatment modality,
      disposition, and any available follow-up. Descriptive statistics were used to
      describe demographics, treatment, and outcome. Outcome measures were defined as
      complications, airway patency, speech, and deglutition. RESULTS: A total of
      16,465 patients were identified from the Trauma Registry as having sustained
      head, neck, or facial injuries, of which 37 patients were diagnosed with
      laryngeal fractures. Complete patient records were available for 27 patients
      (mean age, 35.5 +/- 15.3 years; range, 8 to 80 years; 23 males, 4 females) who
      were classified according to the LEHHC laryngeal injury classification scheme.
      Most patients sustained injuries as the result of blunt trauma (n = 23; 85.1%)
      and almost all of them had concomitant maxillofacial injuries (n = 26; 96.3%).
      Twenty patients (74.1%) required advanced airway intervention (tracheostomy, 14;
      endotracheal intubation, 5; emergent cricothyrotomy, 1), of which 13 patients
      underwent neck exploration. Eight of these patients required open reduction and
      internal fixation with titanium plates and screws, and 2 patients required the
      addition of an endolaryngeal stent. There was a general trend toward poorer
      outcome with increased LEHHC laryngeal injury classification. However, all
      patients were successfully decannulated, maintained patent airways, and ate a
      normal diet. Hoarseness was common in patients who underwent surgical
      exploration; however, long-term perioperative complications were rare and
      included infection requiring hardware removal (n = 1), unilateral vocal cord
      paralysis (n = 1), and subjective dysphagia. CONCLUSION: Fractures of the larynx
      are uncommon injuries that are frequently associated with maxillofacial trauma
      and are potentially associated with significant morbidity. Management of laryngo
      tracheal injuries using a protocol based on airway status as described in this
      report results in airway patency, functional vocal quality, and normal
      deglutition for almost all patients.

PMID- 16413892
TI  - Comparison of remifentanil with fentanyl for deep sedation in oral surgery.
AB  - PURPOSE: The aim of this study was to compare recovery for oral surgery patients
      given a deep sedation regimen of midazolam, propofol, and remifentanil with a
      standard control of fentanyl in place of remifentanil. MATERIALS AND METHODS:
      This investigation was designed as a randomized, prospective, single-blinded
      controlled study. Group 1, the control, received midazolam 0.03 mg/kg, fentanyl 1
      microg/kg, and propofol initially at 140 microg/kg/min. Group 2 received
      midazolam 0.03 mg/kg, remifentanil: propofol (1:500) given at an initial propofol
      infusion rate of 40 microg/kg/min. Outcome measures included time to response to
      verbal command, Aldrete score = 9, Postanesthesia Discharge Scoring System = 7,
      and assessment by the Digit Symbol Substitution Test. RESULTS: Forty-seven
      subjects were entered in the study. Baseline findings were homogenous between the
      2 groups. Subjects in group 2 recovered earlier (P < .005) and required less
      propofol for both the induction (0.8 +/- 0.4 versus 1.2 +/- 0.6 mg/kg; mean +/-
      SD, P < .01) and maintenance of deep sedation (46 +/- 9 versus 131 +/- 17
      microg/kg/min; P < .005). There were minor differences in vital signs.
      CONCLUSIONS: This study demonstrated that this remifentanil regimen provided
      significantly more rapid recovery and used significantly less propofol compared
      with the fentanyl regimen.

PMID- 16413893
TI  - Panoramic imaging of the temporomandibular joint: an experimental study using
      cadaveric skulls.
AB  - OBJECTIVE: The purpose of this study was to determine if condylar morphology can
      be accurately depicted on the panoramic radiograph and if variations in condylar
      anatomy affect the radiographic appearance of the condyle. STUDY DESIGN: The
      shape and angulation of the condyle were determined on 8 cadaveric human skulls.
      Lead foil markers were then placed on the articulating surface and lateral and
      medial pole of each condyle. A panoramic radiograph was made of each skull and
      the position of the markers was assessed. RESULTS: The true shape of the condyles
      was not recognizable on any of the panoramic images. The exact location of the
      articulating surface and medial and lateral poles could not be predicted on the
      panoramic images without markers. The location of these structures varied
      depending on the amount of condylar angulation. CONCLUSION: Because of the
      radiographic variations produced by differences in condylar angulation, it is not
      possible to accurately determine condylar morphology on the panoramic radiograph.
      Therefore, its value in providing the detailed information needed to guide
      diagnosis and treatment of the temporomandibular joint patient is limited.

PMID- 16413894
TI  - Treatment of atrophic mandibular fractures based on the degree of atrophy-
      experience with different plating systems: a retrospective study.
AB  - PURPOSE: The aim of this retrospective study was to evaluate the clinical outcome
      of fractures of the atrophic mandible based on the degree of atrophy and
      treatment by different plating systems. PATIENTS AND METHODS: Thirty patients
      with 40 fractures of atrophic mandibles were treated by open reduction and
      internal fixation at our department between 1994 and 2001. Twelve fractures
      occurred in Class I (between 15- and 20-mm bone height), 10 fractures in Class II
      (between 10 and 15 mm), and 18 fractures in Class III atrophy (<10 mm). The
      profile heights of plating systems used for stabilization varied from 0.5 to 2.2
      mm and were applied with an intraoral (n = 37) and extraoral (n = 3) approach.
      RESULTS: In 36 fractures, bone healing was uneventful. Major complications (loose
      hardware or nonunion) occurred in 4 fractures: 2 in Class II and 2 in Class III
      atrophy. Major complications were observed with 1.4-mm (n = 3) and 2.2-mm (n = 1)
      plates. Minor complications (infections or dehiscence) were observed in 6
      fractures: 3 in Class II and 3 in Class III atrophy. Hypesthesia of the inferior
      alveolar nerve was present 1 week and 1 year postoperatively in 39 and 16
      fractures, respectively. CONCLUSIONS: Treatment of atrophic mandible fractures
      should be based on the degree of atrophy. More rigid fixation may be necessary in
      mandibles with less than 15 mm bone height.

PMID- 16413895
TI  - Endodontic surgery using 2 different magnification devices: preliminary results
      of a randomized controlled study.
AB  - PURPOSE: The introduction of microsurgical instruments and magnification devices
      has brought advantages in root-end management and the application of root-end
      filling materials. The main purpose of this prospective clinical study was to
      monitor the outcome of ultrasonic root-end preparation using magnification loupes
      or an endoscope. Tooth location and the presence of post restoration were also
      examined as potentially affecting the outcome. MATERIALS AND METHODS: Teeth
      treated surgically showed a periradicular lesion of strictly endodontic origin. A
      total of 59 patients were included in the study, according to specific selection
      criteria. Following the reflection of a full mucoperiosteal tissue flap, residual
      soft tissues were curetted, root ends were resected, and root-end cavities were
      prepared ultrasonically with a zirconium nitrate tip, and zinc oxide EBA
      reinforced cement root-end fillings were placed. Thirty-two root-end management
      procedures were performed using magnification loupes and 39 using an endoscope.
      All cases followed for a period of 1 year were classified into 3 groups (success,
      uncertain healing, and failure) according to radiographic and clinical criteria.
      RESULTS: Of the 71 teeth evaluated at 1-year follow-up, 67 teeth (92.95%)
      successfully healed, 3 teeth had uncertain healing, and 2 failed. In the group
      using endoscopy, 94.9% of successful healing was achieved, while for the other
      group, 90.6% was recorded. We found no statistically significant differences in
      treatment results related to the arch (P = .20), post restoration (P = .21), or
      type of magnification device (P = .08). CONCLUSIONS: In the present study,
      adherence to a strict endodontic surgical protocol and the use of modern surgical
      endodontic procedures, together with visual magnifications, resulted in an
      overall high success rate.

PMID- 16413897
TI  - Microscopic changes in the condyle and disc in response to distraction
      osteogenesis of the minipig mandible.
AB  - PURPOSE: Unilateral mandibular distraction osteogenesis (DO) has been shown to
      cause gross changes in the mandibular condyle and articular disc. The purpose of
      this study was to correlate histologic findings with these gross changes in a
      minipig distraction model. MATERIALS AND METHODS: Semiburied distractors were
      placed via submandibular incisions in 15 minipigs. Two unoperated animals served
      as controls. The protocol consisted of 0-day latency and rates of 1, 2, or 4
      mm/day for a 12-mm gap. After the minipigs were killed (at 0, 24, or 90 days),
      ipsilateral and contralateral condyles and discs were harvested, decalcified,
      prepared for standard paraffin embedding, and evaluated to determine changes in
      1) morphology and thickness of the articular cartilage and subchondral bone and
      2) morphology of the disc. RESULTS: In control animals, there were no
      degenerative changes in the articular cartilage and underlying condylar bone;
      there were no significant differences in the mean articular cartilage thickness.
      The temporomandibular joint discs were normal. In experimental animals,
      distracted condyles showed increasing degenerative changes and mean articular
      cartilage thickness as the DO rate increased. The discs were thinner. These
      changes were present, but to a lesser degree, in the contralateral condyles.
      After 90 days, degenerative changes in the condyles and discs were reduced, after
      remodeling, except in the 4 mm/day DO group. CONCLUSIONS: Histologic changes in
      the condyles and temporomandibular joint discs in response to mandibular DO
      correlated with previously reported gross changes. These changes were greater at
      higher distraction rates and remodeling back to normal occurred in mandibular
      condyles distracted at 1 mm/day.

PMID- 16413896
TI  - Cell type and distribution in the porcine temporomandibular joint disc.
AB  - PURPOSE: Surprisingly little is known about the cellular composition of the
      temporomandibular joint (TMJ) disc, which is a crucial piece of the puzzle in
      tissue engineering efforts. Toward this end, cell types were identified and
      quantified regionally in the TMJ disc. MATERIALS AND METHODS: Porcine TMJ discs
      were examined by histology, electron microscopy, and immunohistochemistry.
      Histology consisted of hematoxylin and eosin staining to identify regional
      variation of cell type and cell numbers. Transmission electron microscopy was
      used to elucidate differences in organelle content and pericellular matrix
      between TMJ disc cells and chondrocytes from hyaline cartilage.
      Immunohistochemistry was used to assess the presence of smooth and skeletal
      muscle character in the TMJ disc. RESULTS: The overall ratio of fibroblasts to
      chondrocyte-like cells in the TMJ disc was approximately 2.35 to 1, with the
      highest relative number of chondrocyte-like cells in the intermediate zone.
      Electron microscopy revealed distinct differences between TMJ disc chondrocyte
      like cells and chondrocytes from hyaline cartilage with respect to organelles and
      the pericellular region. Immunostaining identified smooth muscle in the form of
      vessels, which were most prominent in the anterior band. Skeletal muscle was not
      observed. CONCLUSION: The cells of the TMJ disc are distinctly different from
      cells of hyaline cartilage, and consequently should not be referred to as
      chondrocytes. TMJ disc cells are comprised of heterogeneously distributed
      subpopulations, with fibroblasts predominating over fibrochondrocytes.

PMID- 16413898
TI  - Range of curvilinear distraction devices required for treatment of mandibular
      deformities.
AB  - PURPOSE: The purpose of this study was to determine the range of fixed trajectory
      curvilinear distraction devices required to correct a variety of severe
      mandibular deformities. MATERIALS AND METHODS: Preoperative computed tomography
      (CT) scans from 18 patients with mandibular deformities were imported into a CT
      based software program (Osteoplan). Three-dimensional virtual models of the
      individual skulls were made with landmarks to track movements. An ideal treatment
      plan was created for each patient. Upper and lower boundaries for the dimensions
      of curvilinear distractors were established based on manufacturing and geometric
      constraints. Then, anatomically acceptable distractor attachment points were
      identified on the models using proximal and distal grids. Treatment plans were
      simulated for a series of distractors with varying radii of curvature,
      elongations (arc-length of device), and placements along the grids. The outcomes
      using these distractors were compared with the ideal treatment plans.
      Discrepancies were quantified in millimeters by comparing landmarks in the
      simulated versus ideal movements. RESULTS: Approximately 400,000 simulated 3
      dimensional movements, based on the distractor parameters and variations in
      placement were computationally evaluated for the 18 cases. It was determined
      that, by varying distractor placement, a family of 5 distractors, with 3, 5, 7,
      and 10 cm radii of curvature and a straight-line device, could be used to treat
      all 18 cases to within 1.8 mm of error. CONCLUSIONS: The results of this study
      indicate that a family of 5 curvilinear distractors may suffice to treat a broad
      range of mandibular deformities.

PMID- 16413899
TI  - Heat production by 3 implant drill systems after repeated drilling and
      sterilization.
AB  - PURPOSE: The goal was to measure heat generated in bone by 3 implant drill
      systems after repeated drilling and sterilization. MATERIALS AND METHODS:
      Temperature was measured with thermocouple technology in vitro using the bovine
      femoral cortical bone model. Intermittent drilling was accomplished at a constant
      2.4-kg load and drill speed of 2,500 rpm. External irrigation at 40 mL/min with
      normal saline was used. Three implant drill systems-system A (triple twist drills
      with a relief angle), system B (triple twist drills without a relief angle), and
      system C (double twist drills with a relief angle)-were evaluated and heat was
      measured at the final drill in the drilling sequence (4.0 mm or 4.2 mm) at a
      depth of 15 mm. Thermocouples were placed 0.5 mm from the osteotomy at a depth of
      15 mm. Heat measurements were recorded out to 25 uses. RESULTS: Results showed
      temperature increased with multiple uses. System A and C drills had temperature
      measurements that were below 47 degrees C, even after 25 uses. System B drills
      had temperatures that exceeded 47 degrees C from the initial use. Light
      microscopy showed little drill wear even after 25 uses. CONCLUSIONS: Drill
      geometry plays a major role in heat production and may explain the increased
      temperature readings seen in system B. These drills lack relief angles and have
      the smallest clearance angles of the 3 systems. It also has fewer drills in its
      drilling sequence compared with systems A and C. This study shows that
      temperatures increase when drills are used multiple times. Systems A and C had
      acceptable temperature measurements out to 25 uses. System B drills showed
      significantly higher heat production with little visual signs of wear.

PMID- 16413900
TI  - Occupational maxillofacial fractures: a 3-year survey in central Switzerland.
AB  - PURPOSE: The aim of this study was to determine occupational facial fractures in
      central Switzerland. Concomitant injuries were also studied. MATERIALS AND
      METHODS: The Department of Cranio-Maxillofacial Surgery at the University
      Hospital in Berne provides a 24-hour maxillofacial trauma service for its
      population (1.6 million). The present study was comprised of 42 patients (8.4% of
      treated maxillofacial injuries) with occupational maxillofacial fractures
      registered at this unit between 2000 and 2002. Information on the topic of
      occupation, the cause of the accidents, and the topographic location of the
      fractures was analyzed. RESULTS: The mean age of the patients was 44.4 years,
      with a male to female ratio of 41:1. Sixty-nine percent of the injuries occurred
      in farm and forestry workers and in construction laborers during the summertime
      (33%). Workers in these occupations carried a 127-fold (farm and forestry
      workers) and a 44-fold (construction laborers) higher risk of incurring
      maxillofacial fractures than did service and office workers. Injuries were most
      frequently (43%) caused by a thrown, projected, or falling object. Eighty-two
      percent of the fractures occurred in the midface region and at the skull base.
      Fifty-nine percent of the patients had concomitant injuries. In 69%, surgery was
      necessary, the mean duration of their hospital stay being 4.8 days. CONCLUSION:
      The probability of sustaining work-related maxillofacial traumata is correlated
      to the nature of the occupation. Farm and forestry workers are at the highest
      risk, most frequently injured by being struck by an object or an animal. The
      introduction of personalized safety measures should become obligatory in high
      risk occupations.

PMID- 16413901
TI  - The clinical significance of sinus membrane perforation during augmentation of
      the maxillary sinus.
AB  - PURPOSE: Augmentation of the maxillary sinus floor is a well-documented technique
      and is generally accepted as a pure implantology procedure to facilitate
      placement of dental implants in the posterior atrophic maxilla. The objective of
      this report was to evaluate the significance of the sinus membrane perforations
      on the incidence, complications, and success rate of this procedure. PATIENTS AND
      METHODS: Patients who received sinus floor augmentation and simultaneous
      placement of dental implant were included in this study. Subgroup I consisted of
      patients who had their sinus membrane perforated and repaired during the
      procedure with resorbable membrane. Subgroup II consisted of patients whose
      Schneiderian membrane was not perforated during the procedure. The patients were
      followed between 1 to 4 years after augmentation. RESULTS: All perforations were
      classified as class II or III. The success rate of the implants in the
      perforation group was 94.4%, and that for the nonperforation group was 93.9%. The
      difference between the 2 study groups was statistically not significant. A
      significant statistical correlation was found between the residual ridge height
      and the membrane perforation (P < .01). CONCLUSIONS: Mainly due to technical
      difficulties, maxillary sinus membrane perforation occurs more frequently with a
      small height of residual alveolar bone. In this study, no statistical difference
      was observed in the success rate of the immediate implants placed with sinus bone
      grafting in patients whose membrane was perforated versus those patients in whom
      an intact membrane was maintained.

PMID- 16413902
TI  - Preliminary study of tissue-engineered odontogenesis in the canine jaw.
AB  - PURPOSE: We previously reported a method for the development of tissue-engineered
      tooth. However, 1 drawback of the procedure was the inability to determine
      whether the tooth would function when transplanted in the jaw because it was
      formed in the omentum of the abdomen. Therefore, the present study was designed
      to evaluate whether transplantation of dissociated odontogenic cells could induce
      tissue-engineered odontogenesis in the canine jaw. MATERIALS AND METHODS: Cells
      were harvested from canine first molar tooth buds and the resulting heterogeneous
      cell population was seeded on a biodegradable polymer. These constructs were then
      transplanted into the same sockets after extracting the tooth buds. After
      transplantation, we evaluated the transplanted constructs using dental x-ray,
      micro-computed tomography, histology, and immunohistochemistry. RESULTS: After 24
      weeks, micro-x-ray computed tomography showed regenerated hard tissues in the
      jaw, and hematoxylin and eosin staining showed tubular dentin and bone. In the
      regenerated tissue, osteopontin, osteonectin, and osteocalcin antibodies stained
      the dentinal matrix. However, enamel tissue and dental-root formation were not
      observed. CONCLUSION: These data show for the first time the formation of dentin
      and bone from dissociated odontogenic cells in the canine jaw.

PMID- 16413903
TI  - Alveolar segmental sandwich osteotomy for anterior maxillary vertical
      augmentation prior to implant placement.
AB  - Over a 5-year period, 10 partially edentulous patients with anterior vertical
      maxillary deficiency were treated consecutively with segmental osteotomy and
      interpositional bone grafting prior to dental implant placement. Alveolar
      vertical projection and papillary form proved to be stable in all patients up to
      5 years postsurgery. Implant aesthetic results were judged to be satisfactory.
      The technique is an alternative to alveolar distraction osteogenesis but is
      limited to a vertical increase of about 5 mm in the anterior maxilla.

PMID- 16413904
TI  - Implant-borne prosthetic rehabilitation of bone-grafted cleft versus traumatic
      anterior maxillary defects.
AB  - PURPOSE: This study hypothesizes comparable implant success in bone-grafted cleft
      alveolus versus traumatic anterior maxillary defects. Though of different
      pathogenesis, both defects comprise bone deficit, scarred periosteum, and soft
      tissues. Additional complicating factors are isolated. PATIENTS AND METHODS:
      Twenty cleft and 20 traumatic defect cases were followed-up 48 months in average.
      After 9 secondary and 11 tertiary cleft-osteoplasties, 25 implants were inserted;
      in traumatic defects following 8 two-stage and 12 one-stage osteoplasties, 37
      incisor or canine implants were inserted. After secondary and tertiary cleft
      osteoplasties, 57 and 13 months elapsed until implantation, 4 months in the two
      stage posttraumatic osteoplasties. Implants were loaded at 6 months by single
      crowns. RESULTS: Four (20%) cleft patients faced 2 failures and 2 first-year
      losses; 2 (10%) trauma cases faced 2 failures and 2 first-year losses; and
      cumulative 5-year implant success was 80% and 88%, respectively. Other
      parameters' 12-month results were: values for mean cleft, trauma patients (+/-
      standard deviation), significance of comparison in t testing at a cut-off level
      of alpha = 0.05; bone loss 0.3+/-0.5 mm, 0.5+/-0.7 mm, P < .2; Periotest score
      1.1+/-3.1, 1.2+/-2.5, P < .7; gingival recession 2.1+/-0.3 mm, 2.2+/-0.5 mm, P <
      .6; periimplant probing depth 2.5+/-0.5 mm, 2.8+/-2.6 mm, P < .3. CONCLUSION:
      Similar success rates without statistically significant differences were found; a
      multiple factor analysis discerned as positive predictive factors the following;
      generous transplant volume, 3 to 6 months latency, sufficient implant dimension,
      early adulthood. Early loading cannot be encouraged from the success rates.
      Negative predictive factors were spongiosa or milled-bone transplants,
      dehiscence, smoking, and anorexia. Intraorally harvested membranous bone
      transplants may prospectively amend secondary osteoplasty-associated bone
      resorption. Donor site morbidity, local growth, and tooth breakthrough require
      additional observation in a prospective study when implant insertion should
      directly follow the growth spurt.

PMID- 16413905
TI  - Conservative management of a large odontogenic keratocyst: report of a case and
      review of the literature.

PMID- 16413906
TI  - The use of restylane in cosmetic facial surgery.

PMID- 16413907
TI  - Disseminated rhinocerebral mucormycosis: a case report and review of the
      literature.

PMID- 16413908
TI  - Bilateral coronoid hyperplasia in an adolescent: report of a case and review of
      the literature.

PMID- 16413909
TI  - Left posterior lateral pharyngeal space injection during ambulatory general
      anesthesia third molar surgery: a case report.

PMID- 16413910
TI  - A new osteotomy design for surgical expansion of the maxilla: the oblique
      maxillary sagittal osteotomy.

PMID- 16413911
TI  - A modified approach to "model planning" in orthognathic surgery for patients
      without a reliable centric relation.

PMID- 16413912
TI  - Offshore medical degree: are you a physician or a dentist?

PMID- 16413913
TI  - Omission: indications for splinting implant restorations.

PMID- 16413915
TI  - The benefits of strain donation.

PMID- 16413916
TI  - Development of effective vaccines against pandemic influenza.
AB  - A key strategy to protect humans against an influenza pandemic is the development
      of an effective vaccine. However, the development of effective pandemic vaccines
      poses both practical and immunological challenges.

PMID- 16413917
TI  - Marking emerging beta- and gammadelta-selected T cells.
AB  - How does signaling through the pre-TCR and gammadelta TCR generate distinct cell
      lineages? A new study shows that a cell-surface marker, CD27, identifies the
      first point of demarcation of these lineages and allows further probing into the
      critical regulatory factors that control beta and gammadelta selection.

PMID- 16413918
TI  - Taking control of follicular dendritic cells.
AB  - Follicular dendritic cells signal the formation of B cell follicles as well as B
      cell activation, proliferation, and maturation. However, the precise molecular
      pathways controlling these processes are just beginning to be unraveled.

PMID- 16413919
TI  - IL-1 can act as number one.
AB  - Both interleukin-1 receptor (IL-1R) and toll-like receptor 2 (TLR2) signal via
      the adapter molecule MyD88. However, in response to a cutaneous infection
      challenge, the downstream signaling events diverge and IL-1R, but not TLR2,
      proves to be essential for host defense.

PMID- 16413920
TI  - Fcgamma receptors: old friends and new family members.
AB  - Although cellular receptors for immunoglobulins were first identified nearly 40
      years ago, their central role in the immune response was discovered only in the
      last decade. They are key players in both the afferent and efferent phase of an
      immune response, setting thresholds for B cell activation, regulating the
      maturation of dendritic cells, and coupling the exquisite specificity of the
      antibody response to innate effector pathways, such as phagocytosis, antibody
      dependent cellular cytotoxicity, and the recruitment and activation of
      inflammatory cells. Moreover, because of their general presence as receptor pairs
      consisting of activating and inhibitory molecules on the same cell, they have
      become a paradigm for studying the balance of positive and negative signals that
      ultimately determine the outcome of an immune response. This review will
      summarize recent results in Fc-receptor biology with an emphasis on data obtained
      in in vivo model systems.

PMID- 16413921
TI  - Critical function for SIP, a ubiquitin E3 ligase component of the beta-catenin
      degradation pathway, for thymocyte development and G1 checkpoint.
AB  - Beta-catenin has been implicated in thymocyte development because of its function
      as a coactivator of Tcf/LEF-family transcription factors. Previously, we
      discovered a novel pathway for p53-induced beta-catenin degradation through a
      ubiquitin E3 ligase complex involving Siah1, SIP (CacyBP), Skp1, and Ebi. To gain
      insights into the physiological relevance of this new degradation pathway in
      vivo, we generated mutant mice lacking SIP. We demonstrate here that SIP-/-
      thymocytes have an impaired pre-TCR checkpoint with failure of TCRbeta gene
      rearrangement and increased apoptosis, resulting in reduced cellularity of the
      thymus. Moreover, the degradation of beta-catenin in response to DNA damage is
      significantly impaired in SIP-/- cells. SIP-/- embryonic fibroblasts show a
      growth-rate increase resulting from defects in G1 arrest. Thus, the beta-catenin
      degradation pathway mediated by SIP defines an essential checkpoint for thymocyte
      development and cell-cycle progression.

PMID- 16413922
TI  - IkappaBNS inhibits induction of a subset of Toll-like receptor-dependent genes
      and limits inflammation.
AB  - Toll-like receptor (TLR)-mediated immune responses are downregulated by several
      mechanisms that affect signaling pathways. However, it remains elusive how TLR
      mediated gene expression is differentially modulated. Here, we show that
      IkappaBNS, a TLR-inducible nuclear IkappaB protein, negatively regulates
      induction of a subset of TLR-dependent genes through inhibition of NF-kappaB
      activity. IkappaBNS-deficient macrophages and dendritic cells show increased TLR
      mediated expression of genes such as IL-6 and IL-12p40, which are induced late
      after TLR stimulation. In contrast, IkappaBNS-deficient cells showed normal
      induction of genes that are induced early or induced via IRF-3 activation. LPS
      stimulation of IkappaBNS-deficient macrophages prolonged NF-kappaB activity at
      the specific promoters, indicating that IkappaBNS mediates termination of NF
      kappaB activity at selective gene promoters. Moreover, IkappaBNS-deficient mice
      are highly susceptible to LPS-induced endotoxin shock and intestinal
      inflammation. Thus, IkappaBNS regulates inflammatory responses by inhibiting the
      induction of a subset of TLR-dependent genes through modulation of NF-kappaB
      activity.

PMID- 16413923
TI  - Developmental and molecular characterization of emerging beta- and gammadelta
      selected pre-T cells in the adult mouse thymus.
AB  - The first checkpoint in T cell development, beta selection, has remained
      incompletely characterized for lack of specific surface markers. We show that
      CD27 is upregulated in DN3 thymocytes initiating beta selection, concomitant with
      intracellular TCR-beta expression. Clonal analysis determined that CD27high DN3
      cells generate CD4+CD8+ progeny with more than 90% efficiency, faster and more
      efficiently than the CD27low majority. CD27 upregulation also occurs in
      gammadelta-selected DN3 thymocytes in TCR-beta-/- mice and in IL2-GFP transgenic
      reporter mice where GFP marks the earliest emerging TCR-gammadelta cells from DN3
      thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed
      gene expression analysis defined regulatory changes associated with checkpoint
      arrest, with beta selection, and with gammadelta selection. gammadelta selection
      induces higher CD5, Egr, and Runx3 expression as compared to beta selection, but
      it triggers less proliferation. Our results also reveal differences in
      Notch/Delta dependence at the earliest stages of divergence between developing
      alphabeta and gammadelta T-lineage cells.

PMID- 16413924
TI  - FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and
      of antibody responses.
AB  - The FDC-specific molecular signals required in the formation of FDC networks, B
      cell follicles, and germinal centers (GCs) have remained poorly understood. We
      used FDC-specific gene targeting to investigate the function of p55TNFR and IKK2
      in lymphoid organ structure and function. Here we show that FDC-specific
      expression of p55TNFR is necessary and sufficient to promote FDC network and B
      cell follicle formation, restore the expression of CXCL13 and VCAM-1/ICAM-1 in
      FDCs, and lead to productive GCs. Notably, FDC-specific disruption of IKK2 does
      not affect formation of FDC networks. Yet, after antigen engagement or immune
      complex (IC) deposition, FDCs lacking IKK2 fail to upregulate VCAM-1 and ICAM-1,
      and GCs remain sterile. These findings demonstrate that IKK2-independent function
      of p55TNFR on FDCs is sufficient to support the development of FDC networks and
      GCs, while FDC-specific IKK2 is indispensable for the generation of efficient
      humoral immune responses.

PMID- 16413925
TI  - MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation
      in immunity against Staphylococcus aureus.
AB  - MyD88 is an important signaling adaptor for both TLR and IL-1R family members.
      Here, we evaluated the role of TLR2/MyD88 and IL-1R/MyD88 signaling in host
      defense against S. aureus by using a cutaneous infection model in conjunction
      with bioluminescent bacteria. We found that lesions of S. aureus-infected MyD88-
      and IL-1R-deficient mice were substantially larger with higher bacterial counts
      compared with wild-type mice. In contrast, TLR2-deficient mice had lesions that
      were only moderately larger with minimally higher bacterial counts. In addition,
      MyD88- and IL-1R- but not TLR2-deficient mice had severely decreased recruitment
      of neutrophils to the site of infection. This neutrophil recruitment was not
      dependent upon IL-1R/MyD88 signaling by recruited bone marrow-derived cells,
      suggesting that resident skin cells utilize IL-1R/MyD88 signaling to promote
      neutrophil recruitment.

PMID- 16413926
TI  - Recognition of cytosolic DNA activates an IRF3-dependent innate immune response.
AB  - Nucleic acid recognition upon viral infection triggers type I interferon
      production. Viral RNA is detected by both endosomal, TLR-dependent and cytosolic,
      RIG-I/MDA5-dependent pathways. TLR9 is the only known sensor of foreign DNA; it
      is unknown whether innate immune recognition of DNA exists in the cytosol. Here
      we present evidence that cytosolic DNA activates a potent type I interferon
      response to the invasive bacterium Listeria monocytogenes. The noninvasive
      Legionella pneumophila triggers an identical response through its type IV
      secretion system. Activation of type I interferons by cytosolic DNA is TLR
      independent and requires IRF3 but occurs without detectable activation of NF
      kappaB and MAP kinases. Microarray analyses reveal a unique but overlapping gene
      expression program activated by cytosolic DNA compared to TLR9- and RIG-I/MDA5
      dependent responses. These findings define an innate immune response to DNA
      linked to type I interferon production.

PMID- 16413927
TI  - Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis.
AB  - CD8 T lymphocytes are important effectors in protective immunity against
      Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T
      cell activation in tuberculosis mediated by apoptotic vesicles from infected
      cells that transport mycobacterial antigens to dendritic cells (DCs). Here we
      demonstrate that apoptotic vesicles from mycobacteria-infected macrophages
      stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was
      critically required for effective crosspriming. Subsequent fate of vesicle
      associated antigens in recipient DCs was characterized by endosomal mechanisms
      predominating over proteasomal processing. In addition, vesicle processing
      depended on the presence of saposins to disintegrate apoptotic membranes.
      Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll
      like receptors (TLR). Ultimately, vaccination with vesicles from infected cells
      induced protection against M. tuberculosis infection. Taken together, we propose
      the detour pathway to represent a genuine immunological mechanism mediating
      crosspriming of CD8 T cells in vivo and protection against tuberculosis.

PMID- 16413928
TI  - 14-3-3zeta interacts with human thromboxane receptors and is involved in the
      agonist-induced activation of the extracellular-signal-regulated kinase.
AB  - Thromboxane receptor (TP) signaling results in a broad range of cellular
      responses including kinase activation and subsequent nuclear signaling events
      involved in cell transformation, proliferation, and cell survival. Proteins that
      may participate in the early signaling following receptor activation remain to be
      identified. We found that 14-3-3zeta is a novel protein interacting with TP
      intracellular loop 3 (i3) by yeast two-hybrid system. This interaction was
      further confirmed by GST pull-down and co-immunoprecipitation methods. Site
      directed mutagenesis studies indicated that Pro-236 of the TP-i3 was involved in
      the binding to the 14-3-3zeta. Co-immunoprecipitation studies in the same cell
      lysate by TP antibody showed that TP binds not only with the 14-3-3zeta but also
      with the Raf-1. Our data also demonstrated that TP receptor activation induced by
      agonist rapidly recruited 14-3-3zeta and Raf-1 to form a complex with the TP on
      the plasma membrane. The significance of assembling this protein complex was
      examined by TP agonist-induced extracellular-signal-regulated kinase (ERK)
      phosphorylation in intact cells. TP agonist, I-BOP, induced ERK phosphorylation
      in HEK 293 cells expressing wild type TPalpha but significantly lower in those
      expressing TPalpha-P236V mutant. Attenuation of the expression of 14-3-3zeta by
      14-3-3zeta siRNA decreased I-BOP-induced ERK phosphorylation indicating the
      involvement of the 14-3-3zeta in the signal transduction process. These results
      suggest that 14-3-3zeta may serve as a scaffold protein to form a protein complex
      consisting of TP, 14-3-3zeta, and Raf-1, and that this protein complex may be
      involved in the activation of ERK pathway following TP receptor activation.

PMID- 16413929
TI  - The development and validation of a charge-coupled device laser reflectance
      system to measure the complex cross-sectional shape and area of soft tissues.
AB  - Determination of the stresses in soft tissues such as ligaments and tendons under
      uniaxial tension require accurate measurement of their cross-sectional area. Of
      the many methods available, there are concerns regarding contact methods which
      exert external loads and deform the cross-sectional shape of soft tissues. Hence,
      the area measurements are affected. On the other hand, non-contact methods have
      difficulties in dealing with complex shapes, especially with concavities. To
      address these problems, a new measurement system using a charge-coupled device
      (CCD) laser displacement sensor has been developed and tested. This system
      measures the complete surface profile of the object by rotating the laser 360
      degrees around the soft tissue. Then, the cross-sectional shape is reconstructed
      and the cross-sectional area determined via Simpson's rule. The system's accuracy
      was first verified with objects of various cross-sectional shapes and areas
      (cylinder: 23.1, 76.5, 510.3 mm(2); cuboid: 34.3, 163.8, 316.7 mm(2), and
      cylinder with concavities: 121.4 mm(2)). The CCD laser reflectance system's
      accuracy was within 2.0% for these objects. To test biological application, the
      goat Achilles tendon and the anteromedial bundle of the porcine anterior cruciate
      ligament specimens were measured and compared to values obtained using another
      accepted technique, the laser micrometer system. The areas obtained using the CCD
      laser reflectance system were 4.4% and 9.7% lower than those obtained with the
      laser micrometer system respectively. These differences could be mainly
      attributed to concavities. Thus, the CCD laser reflectance system is an improved
      method for measuring the cross-sectional shape and area of soft tissues since it
      can detect and account for concavities without physically contacting the
      specimen.

PMID- 16413930
TI  - A new method for the early diagnosis of brain edema/brain swelling. An
      experimental study in rabbits.
AB  - The aim of the present work is to develop a non-destructive, non-invasive
      technique for the early diagnosis of an oncoming brain edema based on the
      variation of vibration characteristics of the head system (i.e. eigenfrequency
      spectrum and modal damping). Besides the theoretical model that supports the
      basic principle, the proposed technique has been verified experimentally in
      animal tests. The advantage of such an approach is that the relative information
      is available well in advance an increase of intracranial pressure is detected.
      The uncontrolled intracranial hypertension is associated with increased mortality
      or vegetative state in head trauma. Traumatic lesions located on temporal lobe
      render particularly impeding the transtendorial herniation. From the medical
      point of view, intracranial pressure (ICP) monitoring represents an effective way
      for early consideration of neurological decompensation in various neurosurgical
      conditions particularly in the head-injured setting. However, the use of ICP
      monitoring is not an effective way of brain edema detection, since ICP increase
      very often causes irreversible problems to the patient's brain. Therefore, the
      determination of an earlier, less invasive and more sensitive indicator of the
      oncoming intracranial hypertension and of the impeding neurological deterioration
      is of profound importance. The present work aims at experimental verification of
      both eigenfrequency shifting and modal damping increase of the spectral response
      of the head system of rabbits, wherever a mass increase in the content of cranial
      shell appears. The conducted analysis concludes that the eigenfrequency spectrum
      and its modal damping characteristics are sufficiently sensitive parameters in
      order to characterize mass increase in the cranial shell. Therefore the
      combination of both the above parameters could be used with confidence for the
      early diagnosis of brain edema.

PMID- 16413932
TI  - Genomic instability in rat: breakpoints induced by ionising radiation and
      interstitial telomeric-like sequences.
AB  - The Norwegian rat (Rattus norvegicus) is the most widely studied experimental
      species in biomedical research although little is known about its chromosomal
      structure. The characterisation of possible unstable regions of the karyotype of
      this species would contribute to the better understanding of its genomic
      architecture. The cytogenetic effects of ionising radiation have been widely used
      for the study of genomic instability, and the importance of interstitial
      telomeric-like sequences (ITSs) in instability of the genome has also been
      reported in previous studies in vertebrates. In order to describe the unstable
      chromosomal regions of R. norvegicus, the distribution of breakpoints induced by
      X-irradiation and ITSs in its karyotype were analysed in this work. For the X
      irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803
      metaphases were analysed, and a total of 456 breakpoints induced by X-rays were
      detected, located in 114 chromosomal bands, with 25 of them significantly
      affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses
      (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were
      detected, widely distributed in the karyotype of this species. Seventy-six
      percent of all hot spots analysed in this study were co-localised with ITSs.

PMID- 16413931
TI  - Immune responses of locusts to challenge with the pathogenic fungus Metarhizium
      or high doses of laminarin.
AB  - Two isolates of Metarhizium anisopliae var acridum were tested for their effects
      on the locust immune system and for comparison with the effects of challenge by
      injection with laminarin. Isolate IMI 330189 (referred to hereafter as Met 189)
      is highly pathogenic whether applied topically as conidia or injected as
      blastospores. However, isolate ARSEF 728 (referred to hereafter as Met 728) is
      pathogenic only when injected as blastospores, suggesting that the lack of
      pathogenicity of topically applied conidia from this isolate is due to a failure
      to penetrate the insect cuticle and gain access to the haemocoel. After topical
      application of conidia from Met 189, no activation of prophenoloxidase is
      detected, but injection of blastospores from Met 189 brings about a transient
      increase in phenoloxidase activity in the haemolymph in both adult locusts and
      5th instar nymphs, although this does not prevent fungal-induced mortality. Co
      injection of adipokinetic hormone-I (AKH-I) with blastospores prolongs the
      activation of prophenoloxidase in the haemolymph of adult locusts, and enhances
      it in nymphs. It is argued that the lack of activation of prophenoloxidase in
      nymphs shown previously (Mullen, L., Goldsworthy, G., 2003. Changes in
      lipophorins are related to the activation of phenoloxidase in the haemolymph of
      Locusta migratoria in response to injection of immunogens. Insect Biochemistry
      and Molecular Biology 33, 661-670), reflects differences in the sensitivity of
      the immune system between adults and nymphs rather than distinct qualitative
      differences, and this is confirmed in this study by the demonstration that doses
      of laminarin higher than those used previously (>or=100 microg) do activate the
      prophenoloxidase cascade in 5th instar nymphs. Nodules are formed in locusts of
      all ages in response to fungal infection or injection of laminarin, although
      there is wide variation in the number, size and distribution of nodules formed.
      During the examination of 5th instar nymphs for nodule formation, a previously
      unknown phenomenon was observed in which the salivary glands melanise in response
      to injections of blastospores or high doses of laminarin. In c. 85% of such
      nymphs, this reaction is so strong that the whole salivary gland is intensely
      black. Such a response is not observed in the salivary glands of mature adult
      locusts.

PMID- 16413933
TI  - Elimination of organophosphate ester flame retardants and plasticizers in
      drinking water purification.
AB  - Organophosphate ester flame retardants and plasticizers like tris-(2-chloro-, 1
      methyl-ethyl)phosphate (TCPP), tris-(2-chloro-, 1-chloromethyl-ethyl)phosphate
      (TDCP), tris-(2-chloroethyl)phosphate (TCEP), tributylphosphates,
      triphenylphosphate (TPP), ethylhexyldiphenylphosphate (EHDPP) and tris
      (butoxyethyl)phosphate (TBEP) have been studied in diverse processes for drinking
      water purification. The elimination efficiency of these different treatment
      processes, e.g., biological active slow underground passage, soil passage and
      technical treatment processes such as ozonization or multilayer and activated
      carbon filtration have been studied in three waterworks in the catchment area of
      the river Ruhr. In the untreated surface water the concentrations of the
      chlorinated organophosphates ranged 50-150 ng L(-1) TCPP, 10-130 ng L(-1) TCEP
      and 10-40 ng L(-1) TDCP. The amounts of the non-chlorinated alkylphosphates were
      in the same order of magnitude (40 ng L(-1) of the tributylphosphates, 170 ng L(
      1) of TBEP and 10 ng L(-1) TPP) depending on weather and water flow. EHDPP was
      detected in the range of 1 ng L(-1). After the drinking water purification
      process in all waterworks in this study, the concentrations of the selected
      substances were below the respective limit of quantification (0.3-3 ng L(-1)).
      While activated carbon filtration as well as extended passage through soil (10-15
      days residence time) were effective in eliminating all selected compounds,
      ozonization and multilayer filtration did not contribute to the elimination of
      the chlorinated compounds. The elimination effect of slow underground passage
      combined with soil passage concerning the halogenated compounds seemed to depend
      on the hydraulic residence time.

PMID- 16413934
TI  - New estimates of tooth mark and percussion mark frequencies at the FLK Zinj site:
      the carnivore-hominid-carnivore hypothesis falsified.
AB  - Traditional interpretations of hominid carcass acquisition strategies revolve
      around the debate over whether early hominids hunted or scavenged. A popular
      version of the scavenging scenario is the carnivore-hominid-carnivore hypothesis,
      which argues that hominids acquired animal resources primarily through passive
      opportunistic scavenging from felid-defleshed carcasses. Its main empirical
      support comes from the analysis of tooth mark frequency and distribution at the
      FLK Zinj site reported by Blumenschine (Blumenschine, 1995, J. Hum. Evol. 29, 21
      51), in which it was shown that long bone mid-shafts exhibited a high frequency
      of tooth marks, only explainable if felids had preceded hominids in carcass
      defleshing. The present work shows that previous estimates of tooth marks on the
      FLK Zinj assemblage were artificially high, since natural biochemical marks were
      mistaken for tooth marks. Revised estimates are similar to those obtained in
      experiments in which hyenas intervene after humans in bone modification.
      Furthermore, analyses of percussion marks, notches, and breakage patterns provide
      data which are best interpreted as the results of hominid activity (hammerstone
      percussion and marrow extraction), based on experimentally-derived referential
      frameworks. These multiple lines of evidence support previous analyses of cut
      marks and their anatomical distribution; all indicate that hominids had early
      access to fleshed carcasses that were transported, processed, and accumulated at
      the FLK Zinj site.

PMID- 16413935
TI  - When does human ageing begin?
AB  - Through much of the 20th century, the low point of human mortality was seen at 12
      13 years of age. Its stability and timing have been accorded significance in
      terms of evolution, maximal fitness and the onset of ageing. The nadir of
      mortality in developed nations now lies at 5-9 years, significantly predating
      fertility at a mean of 12-13. This differential fall in mortality has resulted in
      England and Wales primarily but not exclusively from reductions in accidents and
      deaths from congenital anomalies. The assumption that the nadir of mortality,
      onset of fertility and a putative intrinsic point of maximal biological fitness
      are synchronous is disproved by this shift. In this paper the logic of inferring
      an individual modal pattern of ageing from mean population behaviour is
      questioned, and the plausibility of the belief that ageing starts at or after
      fertility is examined. Biological ageing, whether seen as 'wear and tear',
      programmed change, or cumulative stochastic damage appears to commence at or
      before conception. Drawing a distinction between 'intrinsic' and 'extrinsic'
      mortality makes less sense in early than in late life, but indicators of
      'intrinsic' diseases are also present from well before fertility. Similarly,
      measures of fitness other than mortality risk may also be argued to diminish from
      before birth.

PMID- 16413936
TI  - Determination of some enzymes and macro- and microelements in stallion seminal
      plasma and their correlations to semen quality.
AB  - Seminal plasma is very important for sperm metabolism as well as sperm function
      and survival and transport in the female genital tract. Analysis of enzyme
      activities and concentrations of elements can estimate integrity and function of
      sperm cell membranes. In man much data are available about biochemical analyses
      of seminal plasma. However, not many studies have been conducted in horses yet.
      We collected ejaculates from 72 stallions, measured the volume, obtained seminal
      plasma by centrifugation and examined spermatozoa with light microscopy for
      motility, concentration, for dead sperm and morphology. Of seminal plasma fluid,
      we measured activities of aspartate-amino-transferase (AST), gamma-glutamyl
      transferase (GGT), alkaline phosphatase (AlP), acid phosphatase (AcP) and lactate
      dehydrogenase (LDH) as well as concentrations of sodium (Na(+)), potassium
      (K(+)), total and ionised calcium (Ca(TOTAL)/Ca(2+)), magnesium (Mg(2+)),
      phosphate (P), chloride (Cl), copper (Cu), iron (Fe) and zinc (Zn). In addition,
      correlations among different parameters in light microscopy and seminal plasma
      were statistically examined by using the Spearman rank correlation coefficient.
      Median enzyme activities for AST, GGT, AlP, AcP and LDH were 80.0, 7,500, 30,200,
      20.0, 81.0 IU/L, respectively. Concentrations of Na(+), K(+), Ca(TOTAL), Ca(2+),
      Mg(2+), P, Cl were 110.5, 22.1, 2.9, 1.7, 3.1, 1.1 and 114.5 mmol/L, and of
      microelements Cu, Fe and Zn were 17.8, 1.9 and 13.2 micromol/L, respectively.
      Furthermore, we found significant correlations between semen volume as well as
      sperm concentration and AST, GGT, AlP, AcP and LDH as well as Fe and Zn. This
      made us propose a primary testicular and epididymal origin of these parameters.
      Significant correlation between GGT and motility may be a sign for its function
      for cell protection against free radicals. LDH activity significantly correlates
      with motility and progressive motility, live:dead-ratio and pathomorphology. In
      our study, LDH seems to be the most predictive enzyme for semen quality. This is
      the first report about GGT, AcP and LDH activities as well as iron in equine
      seminal plasma.

PMID- 16413937
TI  - Mechanisms regulating immune cell contributions to spiral artery modification --
      facts and hypotheses -- a review.
AB  - Early during murine, human and porcine pregnancy, endometrium associated with
      developing placentae is enriched for uterine Natural Killer (uNK) cells. A shared
      role for uNK cells in each of these species is production of angiogenic growth
      factors. Many uNK cells are located in close proximity to or structurally
      integrated within the walls of endometrial vessels. In mice, uNK cells have been
      found essential for the initiation of pregnancy-associated spiral arterial
      modification through their production of interferon-gamma. Unique aspects of uNK
      cell interactions with decidual endothelium are being defined using cell and
      tissue transfer into pregnant, alymphoid mice, adhesion of viable lymphocytes to
      frozen uterine tissue sections under shear forces, laser capture microdissection
      of uNK cells for quantitative RNA analyses and intravital microscopy. These
      studies indicate that uterine lymphocytes have a fundamental and major importance
      in promotion of angiogenesis within implantation sites that is regulated by the
      reproductive hormone cycle. Further, this work suggests that the pro-inflammatory
      endometrial cytokine response seen when peri-implantation conceptuses arrest has,
      as its target for destruction, newly developed endometrial vasculature rather
      than fetal trophoblast.

PMID- 16413938
TI  - The effects of different sample labelling methods on signal intensities of a 60
      mer diagnostic microarray.
AB  - The effects of four different labelling methods on signal intensities of a 60-mer
      diagnostic microarray were studied. Eighty of virus-specific oligonucleotide
      probes for human influenza virus were prepared in an array of 15x16 spots. RNA
      samples from cultured human influenza virus strains were labelled with four
      different methods, including direct cDNA labelling (DL), universal primer
      labelling (UPL), direct cDNA labelling with restriction display (DL-RD), and Cy
      dUTP incorporated cDNA labelling with restriction display (IL-RD) in a signal
      color format. The background-subtracted signal intensities from five replicate
      hybridization experiments of each labelling method were analyzed using one-way
      analysis of variance (one-way ANOVA) and linear regression techniques. The effect
      of sample labelling method on background-subtracted signal intensities was
      significant (p<0.001) and multiple comparisons showed the differences existed
      mainly between DL and the other three labelling methods. The sample labelling
      method explained about 4.3% of signal intensity. The results demonstrated that
      UPL and the RD-based methods are more efficient than the conventional DL method
      for sample labelling, an important variation factor affecting the signal
      intensities in diagnostic microarrays.

PMID- 16413939
TI  - Developing a preclinical model of Parkinson's disease: a study of behaviour in
      rats with graded 6-OHDA lesions.
AB  - Injection of increasing concentrations of 6-hydroxydopamine (6-OHDA) into the
      medial forebrain bundle (MFB) can be used to establish a graded model of
      different clinical stages of Parkinson's disease (PD). We investigated the
      relationship between behavioural alterations and loss of dopaminergic neurons in
      the substantia nigra pars compacta (SNc). Forty female Sprague-Dawley rats were
      injected with either (i) 4 microg (ii) 8 microg or (iii) 16 microg 6
      hydroxydopamine (6-OHDA) to mimic the preclinical, mild and advanced clinical
      stages of PD, respectively. Vehicle was injected in a separate control group.
      Behaviours analysed included postural asymmetry, balance, locomotion,
      sensorimotor deficits and apomorphine rotation. At post-mortem the degree of
      tyrosine immunoreactive dopaminergic cell (TH-ir) loss was then estimated. There
      was a graded and consistent trend in each of the behaviours studied with respect
      to cell loss between the different sized lesion groups when examined using
      correlation analysis (all comparisons, r > 0.8, p < 0.001). Rats with large
      lesions demonstrated more significant behavioural changes over 8 weeks of testing
      than those with intermediate and smaller lesions (group comparisons p < 0.001).
      PD symptomatology became overt when cell loss reached 70%, however some
      significant changes can be observed with as little as 40% dopaminergic cell loss.
      Thus, injection with increasing concentrations 6-OHDA into the MFB can produce
      increasing extents of cell loss and behavioural changes, which were well
      correlated. This graded model can be useful for testing potential neuroprotective
      compounds for PD.

PMID- 16413940
TI  - Exposure of spermatozoa to duroquinone may impair reproduction of the common carp
      (Cyprinus carpio) through oxidative stress.
AB  - Toxicity of many waterborne organic contaminants to aquatic organisms is mediated
      through oxidative damages resulting from the production of reactive oxygen
      species (ROS). Using duroquinone as a model ROS inducer, we carried out in vitro
      and in vivo experiments to test the hypothesis that reproduction in common carp
      (Cyprinus carpio) can be impaired through oxidative damage of their spermatozoa.
      In vitro exposure of fish spermatozoa to 0, 12.5, 25, 50, 100 and 200 microM
      duroquinone for 2 h showed a significant increase in the level of ROS in a dose
      dependant manner. Sperm motility was significantly reduced in all exposure
      groups, but lipid peroxidation (LPO) and DNA strand break (measured by comet
      assay) were only enhanced at 50 microM and above. A significant decrease in
      subsequent hatching rate was recorded in all the exposure groups, despite
      fertilization rate was not affected. In the in vivo experiment, spermatozoa were
      collected 24 and 72 h after fish received intra-peritoneal injections of 1.0 and
      10 mg kg(-1) body weight duroquinone. DNA damage was clearly evident in
      spermatozoa of all treatment groups after 72 h exposure, and ROS was
      significantly enhanced in the high concentration group. LPO however, remained
      unchanged in both treatment groups. The overall results of both our in vitro and
      in vivo experiments demonstrated that duroquinone can induce ROS production in
      spermatozoa, which may impair sperm quality and subsequently reproductive success
      through oxidative stress.

PMID- 16413941
TI  - A robust approach for skewed and heavy-tailed outcomes in the analysis of health
      care expenditures.
AB  - In this paper robust statistical procedures are presented for the analysis of
      skewed and heavy-tailed outcomes as they typically occur in health care data. The
      new estimators and test statistics are extensions of classical maximum likelihood
      techniques for generalized linear models. In contrast to their classical
      counterparts, the new robust techniques show lower variability and excellent
      efficiency properties in the presence of small deviations from the assumed model,
      i.e. when the underlying distribution of the data lies in a neighborhood of the
      model. A simulation study, an analysis on real data, and a sensitivity analysis
      confirm the good theoretical statistical properties of the new techniques.

PMID- 16413942
TI  - Effects of insulin-like growth factor I on the development of osteoblasts in
      hyperglycemia.
AB  - The delayed wound healing of tooth extraction, the activation of alveolar
      absorption and the being hindered bone formation around the implants in diabetes
      are difficult to be solved for dentists. So, the aim of the study was to
      investigate the influences of hyperglycemia and insulin-like growth factor I (IGF
      I) on osteoblasts. Osteoblasts were cultured in different conditions: normal
      glucose, mimic hyperglycemia, hyperglycemia with IGF-I, hyperglycemia with
      insulin. The proliferation and mineralization of osteoblasts were observed. As
      abnormal transport of glucose involved in the development of chronic
      complications in diabetes. The expression of glucose transporter 1 (GLUT1) was
      further evaluated by RT-PCR, immunofluorescence and Western blot in different
      groups. These results showed that hyperglycemia increased the proliferation and
      inhibited the mineralization of osteoblasts, while IGF-I seemed to reverse these
      effects. The levels of GLUT1 mRNA and protein in hyperglycemia were elevated by
      51% and 35%, respectively, compared with that in normal glucose, while the levels
      in hyperglycemia with IGF-I were almost the same as that in normal glucose. In
      conclusion, the increased expression of GLUT1 may contribute to the delayed
      mineralization of osteoblasts in hyperglycemia. Also IGF-I may be a new drug for
      diabetic bone disease through normalizing the expression of GLUT1.

PMID- 16413943
TI  - Low serum dehydroepiandrosterone sulfate concentration is a predictor for
      deterioration of urinary albumin excretion in male patients with type 2 diabetes.
AB  - We recently found that serum dehydroepiandrosterone sulfate (DHEA-S)
      concentration correlated inversely with the degree of urinary albumin excretion
      in a cross-sectional study. We therefore performed an observational study to
      investigate the relationship between serum DHEA-S concentrations and changes in
      urinary albumin excretion in male patients with type 2 diabetes to answer the
      question as to whether DHEA is a causal rather than simply coincidental
      intermediate linking urinary albumin excretion to cardiovascular disease (CVD).
      The relationship between serum DHEA-S concentration and changes in urinary
      albumin excretion was investigated in 207 consecutive male patients with type 2
      diabetes. Baseline serum DHEA-S concentration and urinary albumin excretion were
      measured in 2003. After 12 months, urinary albumin excretion was measured and any
      changes in urinary albumin excretion were calculated. Patients were divided into
      tertiles according to DHEA-S concentration. Greater changes in urinary albumin
      excretion were seen in patients with low DHEA-S concentration (29.6+/-7.6mg/g
      creatinine) than in patients with high DHEA-S concentration (5.1+/-3.6mg/g
      creatinine, P=0.0091). An inverse correlation was observed between serum DHEA-S
      concentration and changes in urinary albumin excretion (r=-0.193, P=0.0052).
      Multiple regression analysis demonstrated that HbA1c (beta=0.241, P=0.0009), and
      serum DHEA-S concentration (beta=-0.195, P=0.0054) were independent determinants
      of changes in urinary albumin excretion. In conclusion, serum DHEA-S
      concentration was inversely correlated with changes in urinary albumin excretion,
      which may indicate causality in the increased CVD mortality in male patients with
      type 2 diabetes and low DHEA-S concentration.

PMID- 16413944
TI  - Insulin resistance is associated with hypertensive response to exercise in non
      diabetic hypertensive patients.
AB  - AIM: Insulin resistance is associated with increased sympathetic activity and
      elevated angiotensin II which may contribute to the excessive increase in
      arterial blood pressure during exercise. In this study, we hypothesized that
      increased insulin resistance will be significantly associated with hypertensive
      response to exercise (HRE) in non-diabetic hypertensive patients. METHOD: Two
      hundred seventy-five hypertensive patients were included in this study. HOMA-IR
      index using serum fasting glucose and insulin was calculated for insulin
      resistance. There were 79 patients with hypertensive response (age 56.1+/-9.4
      years) and 196 patients without hypertensive response (age 53.9+/-8.9 years).
      RESULTS: Insulin resistance, assessed by HOMA index, was significantly higher in
      hypertensive response group as compared to control (HOMA=2.60+/-1.54 versus
      1.76+/-0.86, P<0.001). HOMA was an independent predictor of HRE when controlled
      for age, sex, BMI and baseline SBP (odds ratio=2.008, P<0.001). Also, HOMA was
      significantly correlated with the magnitude of SBP elevation controlled for age,
      sex, BMI and baseline SBP as well (beta=0.293, P<0.001). In conclusion, this
      study shows that insulin resistance is a significant determinant of hypertensive
      response to exercise. Further studies to determine the prognostic significance of
      this finding is warranted.

PMID- 16413945
TI  - Retaining nurses in their employing hospitals and in the profession: effects of
      job preference, unpaid overtime, importance of earnings and stress.
AB  - The purpose of this paper is to examine the effects of job preference, unpaid
      overtime, importance of earnings, and stress in retaining nurses in their
      employing hospitals and in the profession. Data come from our survey of 1396
      nurses employed in three teaching hospitals in Southern Ontario, Canada. Data are
      analyzed first for all nurses, then separately for full-time, part-time, and
      casual nurses. Results show that the key to understanding the effects of these
      variables may be to pay attention to the work status of nurses. With regards to
      retaining nurses in their hospitals, working in their preferred type of job is
      important, particularly for part-time nurses. Working unpaid and longer than
      agreed hours is also a factor for increasing the likelihood of part-time nurses
      to leave the profession. All nurses are less inclined to leave as the importance
      of their earnings for the family increases, but it is particularly important for
      part-time nurses. Stress is an ongoing concern for retaining nurses in their
      hospitals and within the profession. We suggest managers and policy makers pay
      attention to employing nurses in jobs they prefer, decrease unpaid overtime, and
      consider the importance of earnings for them and their families in developing
      policies and programs to retain nurses. More importantly, stress levels should be
      lowered to retain nurses.

PMID- 16413946
TI  - A case of mediastinal emphysema in a 80-year old male.

PMID- 16413947
TI  - Intracellular pH signals in the induction of secondary pathways--the case of
      Eschscholzia californica.
AB  - Transient peaks of the cytoplasmic pH are essential elements in a number of
      signal cascades that activate environmental responses or developmental processes
      in plant cells but little is known about the mechanisms of their generation. In
      many plant cells, elicitation of the hypersensitive response is preceded by a
      perturbation of the ionic balance at the plasma membrane including the inhibition
      of the proton pump and the influx of H+ from the apoplast. A basically different
      mechanism of cytoplasmic acidification that is fed by vacuolar protons has been
      discovered in cell suspensions of the California Poppy (Eschscholzia
      californica). These cells react to a yeast glycoprotein elicitor with the
      overproduction of benzophenanthridine alkaloids. Low elicitor concentrations
      trigger the biosynthesis of these phytoalexins without invoking elements of the
      hypersensitive response. Accumulated data support the existence of a signal path
      that includes the following steps: Links between the above events that connect
      them within a distinct signal path are substantiated by the phenotypes of
      transformed cell lines that either display lowered Galpha levels due to antisense
      transformation or express Galpha-binding antibodies in the cytoplasm. All of
      these cell lines lack the elicitor-activation of PLA2 and of vacuolar proton
      fluxes and show an impaired phytoalexin response to low elicitor concentrations.
      High elicitor concentrations trigger alkaloid biosynthesis via an increase of
      jasmonate at a pH-independent signal path.

PMID- 16413948
TI  - Effects of aging and hormonal status on bimanual motor coordination in the rhesus
      monkey.
AB  - Studies of age-related changes in motor function in nonhuman primates have been
      based exclusively on unimanual motor tasks. In this study, we examined whether
      aging affects bimanual motor coordination in the monkey model. In addition, we
      compared performance of ovariectomized and intact females on the task, to examine
      whether estrogen deficiency impairs motor function. The task required 29 rhesus
      monkeys (6-26 years old) to extract a maximum of 15 raisins from a testing hole
      board. While the task could most efficiently be performed with two hands, other
      motor strategies were possible. The number of raisins extracted per minute was
      measured in each of eight sessions, the first and last of which were videotaped
      for analysis of motor patterns. The number of raisins retrieved per minute
      declined significantly with age. All monkeys improved with practice, but aged
      monkeys improved more slowly than young ones. The proportion of bimanual actions
      tended to increase between the first and the last sessions but was not
      significantly different between young and aged monkeys. Hormonal status did not
      affect performance. Finally, performance on the bimanual task was significantly
      correlated with performance on a previously administered unimanual motor test
      emphasizing speed, suggesting that age-related motor slowing may explain deficits
      in both tasks.

PMID- 16413949
TI  - Economic evaluation of Haemophilus influenzae type b vaccination in Moscow,
      Russian Federation.
AB  - OBJECTIVE: To estimate the cost-effectiveness of providing Haemophilus influenzae
      type b (Hib) vaccine to children in Moscow in routine immunization services.
      METHODS: The incidence of Hib meningitis among children aged <5 years in Moscow
      was obtained from a prospective surveillance study undertaken during October 1999
      September 2001, with treatment cost data collected for all cases. Sequelae in
      surviving children were assessed in December 2002. The costs of Hib vaccination
      in Moscow were estimated assuming a vaccine price of US dollar 5 per dose and the
      same four-dose schedule and 97% coverage as for diphtheria-tetanus-pertussis
      vaccine. The most uncertain variables were varied in a sensitivity analysis.
      RESULTS: The annual incidence of Hib meningitis was 5.7 per 100,000 children <5
      years. The average treatment cost for an acute Hib meningitis case was US dollar
      1296. For a patient with sequelae, the average additional lifetime discounted
      treatment cost was US dollar 15,820. The total annual cost of Hib vaccination of
      infants in Moscow was estimated as US dollar 1.5 million per year. In the base
      case analysis, the cost-effectiveness ratios amount to US dollar 77,503 per Hib
      meningitis case averted and US dollar 10,842 per discounted disability adjusted
      life year averted. The break-even vaccine price, where the annual vaccination
      costs equal annual treatment costs averted, is only US dollar 0.04 per dose in
      the base case scenario. If discounted indirect costs are included, the break-even
      vaccine price is US dollar 0.5 per dose. CONCLUSION: In Moscow, the incidence of
      Hib meningitis is low and the costs of hospitalization and subsequent medical
      treatment are relatively inexpensive. Given these factors, Hib vaccine at US
      dollar 5 per dose would not be a cost-effective option in Moscow at the present
      time.

PMID- 16413950
TI  - Co-administration of IL-12 DNA with rORFF antigen confers long-term protective
      immunity against experimental visceral leishmaniaisis.
AB  - Visceral leishmaniasis, caused by the intracellular parasite Leishmania donovani
      is a significant public health problem in many regions of the world. Anti
      leishmanial immune defences are primarily dependent on the ability of the host to
      mount an interleukin-12 (IL-12) driven Th1 type of responses. Thus, IL-12 plays a
      pivotal role in diversification of the immune responses towards Th1 type. In this
      report, we investigated the effect of IL-12 DNA as an adjuvant with leishmanial
      recombinant open reading frame F (rORFF) protein. We demonstrate that an
      expression plasmid encoding both p35 and p40 subunits of IL-12 when co
      administered with rORFF induces a significant protection with around 82%
      protection in both liver and spleen. The protection correlated with increased
      proliferative response of splenocytes and subsequent release of Th1 cytokine IFN
      gamma. The levels of IFN-gamma were sustained 4 and 8 weeks after challenge with
      L. donovani promastigotes. Interestingly, IL-12 DNA played a key role in
      modulating the antibody response towards IgG2a isotype suggesting its use as a
      potential vaccine adjuvant against intracellular infections like leishmaniasis.

PMID- 16413951
TI  - Genetic stability of live, cold-adapted influenza virus components of the
      FluMist/CAIV-T vaccine throughout the manufacturing process.
AB  - FluMist is a live-attenuated, trivalent influenza vaccine (LAIV) recently
      approved for intranasal administration. To demonstrate genetic stability during
      manufacture of the vaccine viruses in LAIV and a similar vaccine in development
      (CAIV-T), full genome consensus sequences were determined at multiple
      manufacturing stages for four influenza type A and five type B strains. The
      critical cold-adapted (ca), temperature-sensitive (ts) and attenuated (att)
      mutations were preserved in the virus manufacturing intermediates. Moreover,
      sequence identity was observed for all vaccine intermediates of the same strain.
      Minor sequence differences were noted in the shared gene segments of the vaccine
      viruses and their common progenitor master donor virus (MDV) and several of the
      hemagglutinin (HA) and neuraminidase (NA) genes contained nucleotide differences
      when compared to the wild-type parent. Nonetheless, all vaccine viruses retained
      the ca, ts, and att phenotypes. Thus, genetic and phenotypic stability of the
      vaccine viruses is maintained during the manufacture of LAIV/CAIV-T vaccines.

PMID- 16413952
TI  - Herbicide contamination of surficial groundwater in Northern Italy.
AB  - Data on herbicide pollution in groundwater are rather scarce; monitoring data are
      based on single investigation, focussing on limited area and on few compounds of
      interest. The large number of approved active ingredients (approximately 600
      chemicals) makes difficult to obtain an accurate and actual information on
      herbicide application in different countries, even if herbicides are the second
      most important class of pesticides used in the European Union. The results of a
      two-year monitoring campaign undertaken in two areas intensively cultivated at
      Lombardy, Northern Italy, showed a diffuse groundwater contamination due to
      active ingredients and their metabolites. More than 50% of samples overcame
      M.A.C. and the most common herbicides were Atrazine, Terbuthylazine and
      Metolachlor, while DEA and DET metabolites were often characterized by greater
      concentrations than their relative active principles.

PMID- 16413953
TI  - Monitoring losses of copper based wood preservatives in the Thames estuary.
AB  - Field trials were conducted at two sites in the Thames estuary to monitor losses
      of copper, chromium and arsenic from wood preservative treated timbers of varying
      sizes and treatment regimes. Results indicated that leaching tests conducted
      under standard laboratory conditions might overestimate losses compared to losses
      resulting from real environmental exposures. Amine copper treated wood was noted
      to leach higher levels of copper compared to chromated copper arsenate treated
      wood, and was therefore considered an inappropriate replacement biocide for fresh
      and marine construction purposes on this basis. Increases in copper
      concentrations in the outer sections of amine copper treated posts may have
      represented re-distribution of this component in this timber. No accumulation of
      metals was found in sediments surrounding field trial posts.

PMID- 16413954
TI  - Presence of plutonium contamination in soils from Palomares (Spain).
AB  - More than 30 years after the occurrence of an aircraft accident which involved
      the detonation of two nuclear weapons in the surrounding area of the village of
      Palomares (Spain), the affected terrestrial area has been investigated for
      remaining transuranic contamination. Evidence from the presence of this
      contamination was initially found through the analysis of the 241Am inventories
      in superficial soil samples collected in the region, and was confirmed through
      the analysis of the (239+240)Pu inventories and their associated
      238Pu/(239+240)Pu activity ratios in the same samples. However, it was also
      observed that a considerable fraction of the remaining contamination in the area
      was present in particulate form, i.e. as "hot particles". The work performed in
      our laboratory for identification, isolation and characterisation of these "hot
      particles" as well as some conclusions obtained from these analyses are outlined
      in this paper.

PMID- 16413955
TI  - Neurofilament phosphorylation and disruption: a possible mechanism of chronic
      aluminium toxicity in Wistar rats.
AB  - The present study was designed to investigate the possible effects of chronic
      aluminium exposure on neurofilament phosphorylation and its subsequent disruption
      in various regions of the rat brain. An intra-gastric dose of aluminium (10mg/kg
      bw for 12 weeks) resulted in a marked enhancement of Ca2+/CaM dependent protein
      kinase activity as compared to cAMP dependent protein kinase. The levels of
      phosphoprotein phosphatase were found to be significantly depleted only in the
      cerebral cortex. After in vitro phosphorylation using [32gamma-P] ATP, various
      proteins were resolved on one-dimensional 8% SDS-PAGE, stained with Coomassie
      Blue and autoradiographed. The amount of 32P-incorporated was quantified using
      ADOPE PHOTOSHOP (7.0). The 200 kDa neurofilament protein was identified using
      immunoblotting. Finally, the extent of phosphorylation induced neurofilamentous
      damage was assessed using immunocytochemical studies. The cytoskeletal proteins
      were found to be aggregated and disrupted in all the three neuronal regions
      following 12 weeks of aluminium treatment. This study lends further support to
      the possible role of aluminium as a potent neurotoxic agent and in the
      etiopathogenisis of various neurodegenerative diseases.

PMID- 16413956
TI  - Hoffstater-Cullen-Hellendal sign in ruptured tubal pregnancy in a patient with
      uterus didelphys and vagina duplex.

PMID- 16413957
TI  - Laparoscopic partial nephrectomy in renal cell cancer--results and
      reproducibility by different surgeons in a high volume laparoscopic center.
AB  - OBJECTIVES: With increasing surgical skills and novel methods of hemostasis
      laparoscopic Partial nephrectomy has become an attractive treatment option for
      selected renal tumors. We report techniques, perioperative data and oncological
      outcome in a single center experience with three different surgeons. PATIENTS AND
      METHODS: Between March 2001 and October 2004, 44 patients underwent laparoscopic
      transperitoneal partial nephrectomy for exophytic tumors. Median tumor size was 3
      cm (1-5 cm). In 25 cases the renal artery was clamped using endoscopic bulldog
      clamps and tumor resection was performed with scissors or the harmonic scalpel.
      Hemostasis was achieved by application of FloSeal only; closure of the collecting
      system with Lahodny sutures was performed, if necessary. Frozen sections were
      obtained in all cases. RESULTS: All procedures were successful with no
      intraoperative complications. Mean surgical time was 210 min (115-355 min);
      clamping time was 21 min (7-41 min) in 25 cases. In 8 cases suturing of the
      collecting system was required. Margins were negative in 37 cases, in five cases
      secondary resection was necessary to achieve negative margin status; in two cases
      radical nephrectomy was performed. There were no significant differences between
      surgeons in terms of patient data and results. At a mean follow-up of 15 months
      (6-37 months) no recurrence was observed. CONCLUSIONS: Laparoscopic partial
      nephrectomy using FloSeal is a feasible and safe method for treatment of small
      renal masses. The technique is reproducible by surgeons who are used to complex
      laparoscopic procedures like expected in high volume laparoscopic centers.

PMID- 16413958
TI  - Search for function and modulation of enzyme activity. Proceedings of the
      international workshop on 11beta and 17beta-hydroxysteroid dehydrogenases. May 8
      11, 2005. Elmau Castle, Germany.

PMID- 16413959
TI  - Amphibian metamorphosis as a model for the developmental actions of thyroid
      hormone.
AB  - Thyroid hormone (TH) elicits multiple physiological actions in vertebrates from
      fish to man. These actions can be divided into two broad categories: those where
      the hormone regulates developmental processes and those that involve actions in
      the adult organism. Amphibian metamorphosis is a most dramatic example of
      extensive morphological, biochemical and cellular changes occurring during post
      embryonic development, which is obligatorily initiated and sustained by TH. It
      is, therefore, an ideal model system to understand the action of the hormone.
      Each tissue of the frog tadpole responds differently to TH, ranging from altered
      gene expression, morphogenesis, tissue re-structuring and extensive cell death,
      according to a developmental programme set in place before the thyroid gland
      begins to secrete the hormone. The key element determining the response to the
      hormone is the nuclear thyroid hormone receptor (TR). As in most vertebrates,
      there are two thyroid hormone receptors, TRalpha and TRbeta, which repress
      transcription in the absence of the ligand and whose concentration in the tissues
      is directly modulated by the hormone itself. In Xenopus, biochemical and in situ
      techniques have shown that the amount of TRbeta mRNA and protein are elevated 50
      100 times during TH-induced metamorphic climax. This phenomenon of
      "autoinduction" of receptor is also seen with developmental or inductive
      processes regulated by other hormones acting through nuclear receptors. It is
      possible that receptor upregulation may be a pre-requisite for hormonal response.
      Recent molecular and cell biological studies have suggested that TRs function as
      multimeric complexes with other nuclear or chromatin proteins, such as co
      repressors and co-activators, to regulate the structure of the chromatin, and
      thereby determine the transcription of the receptor-specified target gene. There
      is evidence that this may also be so for thyroid hormone regulated transcription
      during amphibian metamorphosis.

PMID- 16413960
TI  - Multifunctionality of human 17beta-hydroxysteroid dehydrogenases.
AB  - 17Beta-hydroxysteroid dehydrogenases (17beta-HSDs) belong to the family of short
      chain dehydrogenases/reductases (SDRs) and aldoketo-reductases (AKRs). Some of
      the enzymes were discovered and named due to their enzymatic activity on steroid
      substrates or according to their sequence homology to other 17beta-HSDs. During
      characterisation of these enzymes it turned out that their substrate specificity
      is broader than first expected and key functions of some 17beta-HSDs in vivo are
      probably not in steroid metabolism but in basic metabolic pathways. The issue of
      such multifunctionality is the topic of this review.

PMID- 16413961
TI  - Accumulation of irreversible disability in multiple sclerosis: from epidemiology
      to treatment.
AB  - There is convincing evidence that neurological relapses in multiple sclerosis
      (MS) are the clinical counterpart of acute focal inflammation of the central
      nervous system (CNS) whereas neurological progression is that of chronic diffuse
      neurodegeneration. The classical view is to consider that MS is an organ-specific
      autoimmune disease, i.e. that inflammation is the cause of the neurodegeneration.
      The succession of relapses eventually leads to accumulation of disability and
      clinical progression results from subclinical relapses. A series of recent
      observations tends to challenge this classical concept. Important observations
      have come from the study of the natural history of MS. In the Lyon MS cohort,
      accumulation of irreversible disability appeared not to be affected by clinically
      detectable neurological relapses. This has also been shown to be "amnesic" for
      the early clinical characteristics of the disease, and essentially age-dependent.
      Suppressing relapses by disease-modifying agents does not dramatically influence
      the progression of irreversible disability. Interferons beta reduce the relapse
      rate by 30% and conventional MRI activity by more than 50%. In spite of this
      effect on inflammation, the effect on disability is only marginal and possibly
      relapse-reduction-dependent. Administration of Campath-1H to patients with very
      active disease in terms of frequency of relapses, accumulation of disability and
      MRI activity, results in a profound, prolonged lymphopenia and the suppression of
      clinical and MRI activity, but in spite of this, clinical disability and cerebral
      atrophy still progress. The same experience has been reported with cladribine and
      autologous haematopoietic stem cell transplantation. All these observations give
      support to the fact that relapses do not essentially influence irreversible
      disability in the long term in MS. They are consistent with what has been shown
      at the individual level in the 1970s by performing serial quantitative
      neurological examinations over several years, and with what is currently emerging
      from early and serial structural brain MRI studies. These breakthroughs have
      immediate implications for the counselling of patients with MS. They suggest that
      MS is as much neurodegenerative as inflammatory, and should cause the
      modification of disease-modifying therapeutic strategies by focussing on the
      protection and repair of the nervous system and not only on the control of
      inflammation.

PMID- 16413962
TI  - Neuroprotection in multiple sclerosis.
AB  - In chronic inflammatory diseases like multiple sclerosis (MS), neuroprotection
      refers to strategies aimed at prevention of the irreversible damage of various
      neuronal and glial cell populations, and promoting regeneration. It is
      increasingly recognized that MS progression, in addition to demyelination, leads
      to substantial irreversible damage to, and loss of neurons, resulting in brain
      atrophy and cumulative disability. One of the most promising neuroprotective
      strategies involves the use of bone marrow derived stem cells. Both hematopoietic
      and non-hematopoietic (stromal) cells can, under certain circumstances,
      differentiate into cells of various neuronal and glial lineages. Neuronal stem
      cells have also been reported to suppress EAE by exerting direct in situ
      immunomodulating effects, in addition to their ability to provide a potential
      source for remyelination and neuroregeneration. Preliminary results from our
      laboratory indicate that intravenous or intracerebral/intraventricular injection
      of bone marrow derived stromal cells could differentiate in neuronal/glial cells
      and suppress the clinical signs of chronic EAE. Both bone marrow and neuronal
      stem cells may therefore have a therapeutic potential in MS. It seems that future
      treatment strategies for MS should combine immunomodulation with neuroprotective
      modalities to achieve maximal clinical benefit.

PMID- 16413963
TI  - On the coincidence of cervical spondylosis and multiple sclerosis.
AB  - Multiple sclerosis (MS) and cervical spondylosis are relatively common diseases.
      It is therefore inevitable that the MS clinician will be confronted with patients
      with myelopathy in whom the two conditions coexist. When faced with an MS patient
      who has cord compression secondary to cervical spondylosis as well as cord
      demyelination, the issue of surgical decompression of the cord arises. Whether
      the trauma of cord compression aggravates the MS lesions is still a matter of
      debate and should not influence treatment decisions. There is little prospective
      evidence-based support for the notion of surgical cord decompression in cervical
      spondylosis without MS, and none at all for surgery in MS, with only small
      published retrospective series available. The clinician must therefore make a
      judgment-based treatment decision. Guidelines for the management of patients with
      coincidental cervical cord compression and MS are suggested.

PMID- 16413964
TI  - Multiple sclerosis: postlinkage genetics.
AB  - Because of the relative failure of linkage analysis in multiple sclerosis,
      despite the investigation of more than 700 affected relative pairs, we have
      applied four alternative strategies to identify genes that confer susceptibility
      to the disease. First, we have reported two clusters of MS patients from isolated
      populations where 19 and 13 patients, respectively, could be shown to have common
      ancestry tracing back several centuries. Three and five haplotypes, respectively,
      were shown to be shared by affected individuals, however, these haplotypes were
      extended and the statistical evidence modest. Second, we have recently reported
      the results of a two-stage candidate gene analysis of 66 selected genes, mostly
      of immune function. The IL-7 receptor alpha gene and LAG-3 both had three SNP
      markers associated with MS. Third, we recently identified the MHC class II
      transactivator gene in an animal model with inflammatory properties and later
      confirmed it to be of importance for MS, rheumatoid arthritis and acute
      myocardial infarction. Finally, in collaboration with the Serono Genetics
      Institute, we have completed a genome-wide screen with over 100,000 markers in
      three sets of 300 MS patients and 300 matched controls. Eighty genes showed
      evidence of importance in all three populations. These strategies appear to hold
      some promise of success where linkage analysis has proven less successful than
      anticipated.

PMID- 16413965
TI  - Pregnancy and multiple sclerosis: the children of PRIMS.
AB  - The influence of pregnancy on multiple sclerosis (MS) has long been a matter of
      controversy. Women with MS were often discouraged to consider pregnancy. The
      PRegnancy In Multiple Sclerosis (PRIMS) study was the first large prospective
      study aimed at assessing the possible influence of pregnancy and delivery on the
      clinical course of MS. Two hundred and fifty-four women with the diagnosis of MS
      were included during pregnancy and followed until the end of the second year post
      partum. The results were a reduction in the relapse rate during pregnancy, in
      comparison to the year before pregnancy, especially marked in the third
      trimester, and a significant increase in the relapse rate in the first trimester
      post partum. Starting in the second trimester post partum, the relapse rate did
      not significantly differ from the pre-pregnancy rate. About one third of the
      women experienced a post partum relapse. Pregnancy did not influence disability
      progression. Women with greater disease activity in the year before and during
      pregnancy had a higher risk of relapse in the first three months post partum.
      Neither breastfeeding, nor epidural analgesia correlated with the presence of a
      post partum relapse. When comparing predicted and observed status, 72% of the
      women were correctly classified by the multivariate model; it therefore seems
      unwise to use such a model to select women who would benefit from a putative
      preventive therapy. The PRIMS study had other major consequences: it fostered the
      development of specific therapeutic strategies to prevent post partum relapses
      (i.v. immunoglobulins, i.v. methylprednisolone), and suggested a potential role
      for sex hormones in the natural history of MS during pregnancy and the post
      partum. The preventive effect of progesterone combined with estradiol on post
      partum relapses is about to be tested in a large randomized and placebo
      controlled European trial, the POPART'MUS study.

PMID- 16413966
TI  - Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2
      nonenal, in brain from persons with mild cognitive impairment.
AB  - Oxidative damage is a feature of many age-related neurodegenerative diseases,
      including Alzheimer's disease (AD). 4-Hydroxy-2-nonenal (HNE) is a highly
      reactive product of the free radical-mediated lipid peroxidation of unsaturated
      lipids, particularly arachidonic acid, in cellular membranes. In the present
      study we show for the first time in brain obtained at short postmortem intervals
      that the levels of HNE are elevated in mild cognitive impairment (MCI)
      hippocampus and inferior parietal lobules compared to those of control brain.
      Thus, increased levels of HNE in MCI brain implicate lipid peroxidation as an
      early event in AD pathophysiology and also suggest that the pharmacologic
      intervention to prevent lipid peroxidation at the MCI stage or earlier may be a
      promising therapeutic strategy to delay or prevent progression to AD.

PMID- 16413967
TI  - The lack of bicuculline and picrotoxin influence on midazolam depressant action
      on brain oxygen consumption.
AB  - In the previous study of the rat frontal cortex slices oxygen consumption (QO2),
      polarographically determined using the biological oxygen monitor, a moderate
      respiratory depressant action of midazolam ex vivo (1.0 mg/kg) has been observed.
      Antagonist of the benzodiazepine binding site, flumazenil, blocked the effect of
      the agonist. However, midazolam-gamma-aminobutyric acid (GABA) interactions
      pointed to the possibility that a part of midazolam action is independent of the
      classical GABA potentiation. To test this presumption, GABAA receptor antagonists
      bicuculline and picrotoxin were administered. Both blockers antagonized the QO2
      reducing effect of the combination of per se effective doses of midazolam (1.0
      mg/kg) and GABA (5 x 10(-4) mol/l), as well as of GABA (5 x 10(-4) mol/l) itself.
      However, neither effects of midazolam (1.0 mg/kg) on its own, nor those of
      midazolam in presence of the physiological, per se ineffective, concentration of
      GABA (10(-6) mol/l), were susceptible to antagonism. These results show that ex
      vivo influence of midazolam on cerebral metabolic activity should be partly
      ascribed to some of its cellular mechanisms probably associated to the GABA
      modulation, but distinct from the standard GABA-potentiating effects of
      benzodiazepines.

PMID- 16413968
TI  - Fluoxetine increases the nitric oxide production via nuclear factor kappa B
      mediated pathway in BV2 murine microglial cells.
AB  - A body of recent evidence implicates that antidepressants affect the inflammatory
      response and immune system. The present study is focused on the effects of the
      most widely used antidepressant agent, fluoxetine on the production of nitric
      oxide (NO) in BV2 microglial cells. In this study, we observed interesting result
      that NO production was increased by fluoxetine. The mRNA level of nitric oxide
      synthase (iNos, Nos2) by RT-PCR was also stimulated by fluoxetine. We next
      conducted electophoretic mobility shift assay (EMSA) to determine the DNA binding
      activity of nuclear factor kappa B (Nfkappab), an important upstream modulator
      for Nos2 expression, to find that fluoxetine increased DNA binding activity of
      Nfkappab. By Western blot analysis, phosphorylation levels of p38 mitogen
      activated protein kinase (p38 Mapk, Mapk14) and extracellular signal-related
      kinase (Erk)1/2 Mapk, upstream signaling mediators of Nfkappab were found to be
      increased by fluoxetine. In addition, the mRNA expressions of other
      proinflammatory cytokines, interleukin 6 (Il6) and tumor necrosis factor alpha
      (Tnfalpha) were examined. The expressions of both Il6 and Tnfalpha by fluoxetine
      treatment were similar to those of Nos2 and Nfkappab. Taken together, our results
      show that fluoxetine stimulates NO production via Nfkappab-mediated pathway in
      BV2 cells.

PMID- 16413969
TI  - Any way you look at it, successful obstacle negotiation needs visually guided on
      line foot placement regulation during the approach phase.
AB  - In the two experiments discussed in this paper we quantified obstacle avoidance
      performance characteristics carried out open loop (without vision) but with
      different initial visual sampling conditions and compared it to the full vision
      condition. The initial visual sampling conditions included: static vision (SV),
      vision during forward walking for three steps and stopping (FW), vision during
      forward walking for three steps and not stopping (FW-NS), and vision during
      backward walking for three steps and stopping (BW). In experiment 1, we compared
      performance during SV, FW and BW with full vision condition, while in the second
      experiment we compared performance during FW and FW-NS conditions. The questions
      we wanted to address are: Is ecologically valid dynamic visual sampling of the
      environment superior to static visual sampling for open loop obstacle avoidance
      task? What are the reasons for failure in performing open loop obstacle avoidance
      task? The results showed that irrespective of the initial visual sampling
      condition when open loop control is initiated from a standing posture, the
      success rate was only approximately 50%. The main reason for the high failure
      rates was not inappropriate limb elevation, but incorrect foot placement before
      the obstacle. The second experiment showed that it is not the nature of visual
      sampling per se that influences success rate, but the fact that the open loop
      obstacle avoidance task is initiated from a standing posture. The results of
      these two experiments clearly demonstrate the importance of on-line visual
      information for adaptive human locomotion.

PMID- 16413970
TI  - On the importance of precise calibration techniques for an atomic force
      microscope.
AB  - Proper calibration of any instrument is vital to an investigator's ability to
      compare laboratory experiments, as well as to draw quantitative relations between
      experimental results and the real world. For the atomic force microscope,
      knowledge of quantities such as the probe spring constant, the piezoactuator
      voltage/height response, and the probe radius of curvature is necessary when
      transforming raw data into height, separation and force. These parameters are
      also prerequisites when applying mathematical models to the collected data. In
      this communication, we adapt existing techniques of quantifying these parameters
      to our equipment and show differences between the adjusted parameters and those
      provided by the manufacturer. The total statistical uncertainty attributable to
      these parameters was calculated as > 1500% using the manufacturers' values. After
      adjustment, this contribution drops to approximately 20%. The combined effect of
      quantifying these parameters, which had previously not been explored in concert,
      demonstrates the necessity of properly understanding one's equipment in order to
      generate reproducible and credible experimental results.

PMID- 16413971
TI  - Prevalence and potential risk factors for organophosphate and pyrethroid
      resistance in Boophilus microplus ticks on cattle ranches from the State of
      Yucatan, Mexico.
AB  - A cross-sectional study was carried out in order to investigate the association
      between management risk factors and the prevalence of organophosphate (OP) and
      synthetic pyrethroid (SP) resistance in Boophilus microplus ticks in Yucatan
      State, Mexico. Ninety-eight cattle ranches were randomly selected and a sample of
      20-30 engorged female B. microplus ticks was collected at each. The modified
      larvae packet test was used to detect OP and SP tick resistance. A questionnaire
      was administered on each ranch. For risk factors, four reference types of
      response were used: Tuxpan (resistant to coumaphos, chlorfenvinphos and
      diazinon), Parkhurst (resistant to flumethrin, deltamethrin and cypermethrin),
      Lamington (resistant to flumethrin in absence of deltamethrin and cypermethrin)
      and Marmor (resistant to flumethrin and cypermethrin in absence of flumethrin). A
      primary screening was performed using 2 x 2 contingency tables of exposure
      variables. All variables with p < or = 0.20 were analyzed by a logistic
      regression. The prevalence of B. microplus resistance to OP and SP groups were
      83.70% and 66.32%, respectively. The prevalence for a single chemical compound
      was: diazinon (80.60%), coumaphos (45.90%), chlorfenvinphos (35.70%), flumethrin
      (63.28%), deltamethrin (61.22%), and cypermethrin (59.18%). The prevalence type
      of response was: Tuxpan (34.16%), Parkhurst (58.16%), Lamington (4.08%), and
      Marmor (4.08%). The use of a different tick control program was the risk
      management factor associated with the Parkhurst type of response. It is concluded
      that the prevalence of cattle ranches with B. microplus resistant to OPs and SPs
      in Yucatan, Mexico, is a current problem, and a treatment interval of > or =6
      times/year and use of a tick control program (macrocyclic lactones and pasture
      burn) different from standard recommended programs are risk factors associated
      with the Parkhurst type of response.

PMID- 16413973
TI  - Modulation of the hypothalamo-pituitary-adrenocortical axis by caffeine.
AB  - Although caffeine is the most consumed psychoactive substance in the world, the
      extents of many of its effects are unknown. High doses of caffeine have been
      shown to activate the HPA axis while the effects of low to moderate doses have
      usually not been described in detail. Moreover, although several lines of
      evidence suggest that low doses of caffeine may restrain some negative affective
      states, the possible modulatory role of caffeine on HPA axis activation induced
      by a stressful stimulus has not been described. Thus, the present studies
      investigated the possible modulatory effects of low to moderate doses of caffeine
      on moderate to high HPA axis activation induced by different intensities of loud
      noise. First, in order to test this modulation, time courses for
      adrenocorticotropic hormone (ACTH) and corticosterone responses to loud noise
      stress and to caffeine were defined, in rats. Plasma ACTH and corticosterone
      levels peaked 30 min from the onset of noise presentation, and rapidly declined
      after noise termination. A low caffeine dose of 2 mg/kg significantly increased
      plasma corticosterone and ACTH levels 30 min following injections, but levels
      returned to baseline 60 min following injections. Caffeine doses of 30 mg/kg and
      higher elevated plasma hormone levels for at least 2h. Doses of 2 or 10mg/kg,
      however, did not modulate endocrine responses to loud noise presentation. It is
      concluded that although caffeine activates the HPA axis, low to moderate doses do
      not modulate HPA axis responses to stressful stimuli.

PMID- 16413974
TI  - Effects of partial reinforcement and time between reinforced trials on terminal
      response rate in pigeon autoshaping.
AB  - Partial reinforcement often leads to asymptotically higher rates of responding
      and number of trials with a response than does continuous reinforcement in pigeon
      autoshaping. However, comparisons typically involve a partial reinforcement
      schedule that differs from the continuous reinforcement schedule in both time
      between reinforced trials and probability of reinforcement. Two experiments
      examined the relative contributions of these two manipulations to asymptotic
      response rate. Results suggest that the greater responding previously seen with
      partial reinforcement is primarily due to differential probability of
      reinforcement and not differential time between reinforced trials. Further, once
      established, differences in responding are resistant to a change in stimulus and
      contingency. Secondary response theories of autoshaped responding (theories that
      posit additional response-augmenting or response-attenuating mechanisms specific
      to partial or continuous reinforcement) cannot fully accommodate the current body
      of data. It is suggested that researchers who study pigeon autoshaping train
      animals on a common task prior to training them under different conditions.

PMID- 16413976
TI  - Construction and characteristics of 3-end enriched cDNA library from individual
      embryos of cattle.
AB  - To analyze stage-specific gene expression profiles of pre-implantation embryos
      and evaluate potential viability, techniques were adapted to generate 3-end
      enriched cDNA libraries from individual embryos of cattle based on RT-PCR
      methodology. The reproducibility of constructing a cDNA library was tested by
      five independent PCR experiments with specific primers for the presence of
      several rare genes such as DNMT1 (DNA methylation transferase 1), DNMT2, DNMT3A,
      Oct-4/3 (octmer-binding transcription factor), IFN-iota, IGF-2r (insulin like
      growth factor 2 receptor), and the housekeeping genes, H2A and beta-actin.
      Results indicated repeatability and that a proportion of expressed genes in the
      cDNA library from an individual embryo was not affected by limited PCR
      amplification. From the cDNA library, 134 clones were randomly selected for
      sequencing and showed that structure related elements accounted for 33.5% of
      transcripts and the energy- and metabolism-related genes were also an important
      component being 11.9% in the cDNA library. Approximately 14% of genes in the
      library were functionally unknown including greater than 5% of genes that were
      likely novel because there was no identity in Genbank. The frequency of structure
      related genes such as beta-actin and ribosomal proteins in the cDNA library
      corresponded to other reports and suggested that the cDNA library constructed by
      RT-PCR might be proportional to the mRNA populations. The cDNA libraries
      constructed from different stage embryos will provide a powerful tool to explore
      novel genes relevant to embryogenesis, determine the profiling of stage-specific
      gene expression, and evaluate the potential viability of embryos.

PMID- 16413975
TI  - Dopamine agonists and antagonists can produce an attenuation of response bias in
      a temporal discrimination task depending on discriminability of target duration.
AB  - The current study examined the effects of the D2 agonist (quinpirole) and D2
      antagonist (eticlopride) on temporal discrimination performance in a conditional
      discrimination task (Experiment I) and a delayed conditional discrimination task
      (Experiment II). In both experiments rats discriminated between a scheduled
      stimulus duration of 3 s versus 9 s. Consistent with previous reports, overall
      discrimination performance decreased in a dose-dependent manner with both drugs.
      Changes in response bias (the tendency to choose-short or choose-long
      irrespective of actual stimulus duration), however, were best characterized in
      terms of both drugs tending to attenuate the bias effects normally observed
      during baseline drug-free performance. Specifically, the 'choose-short' bias
      observed in Experiment I and at a relatively short, 0.1 s, delay in Experiment II
      became less extreme with increasing doses. In addition, the 'choose-long' bias
      observed at a relatively long, 6 s, delay in Experiment II also became less
      extreme with increasing doses. Thus, whether there was an apparent shift from a
      short response bias to long, or vice versa, was the product of the delay interval
      between stimulus presentation and choice rather than whether the drug in question
      was a D2 agonist or antagonist. Such an attenuation of bias may have arisen
      because of subjects confounding the delay interval with the actual discriminative
      stimulus duration.

PMID- 16413977
TI  - Menopausal women's positive experience of growing older.
AB  - OBJECTIVE: This paper aims to describe menopausal women's positive experience of
      growing older and becoming middle-aged. METHODS: Qualitative interviews with 24
      menopausal women, selected on the basis of a questionnaire, covering a broad
      spectrum of Danish women in terms of experience of menopausal symptoms,
      treatment, contact with the health care system, and social background. RESULTS:
      The women expressed varied and many-facetted views on ageing and clearly
      connected the fact that they were menopausal to the ageing process. All, except
      one, mentioned positive aspects of growing older: 1. they had become more
      experienced and competent; 2. they had gained more freedom; 3. they perceived
      possibilities of personal development that made them able to hold on to their own
      opinions and better speak their minds. The described positive effects were the
      result of having lived a long life, of good and evil, not of the menopause
      itself. The women also mentioned negative aspects: 1. negative expectations; 2.
      negative experiences. Positive aspects, often of psychological or existential
      nature, seemed to outweigh the negative experiences which were mostly related to
      bodily changes or losses. CONCLUSION: This paper discusses the importance of
      avoiding unnecessary negative expectations of ageing and menopause and of
      focusing, instead, on the positive aspects of growing older. Health professionals
      should reconsider the necessity to talk about future risks with healthy women,
      and instead support the women's agenda when they try to cope with real-life
      problems.

PMID- 16413978
TI  - Hydrophilic matrices: application of Placket-Burman screening design to model the
      effect of POLYOX-carbopol blends on drug release.
AB  - The aim of the present study was to screen the effect of seven factors--POLYOX
      molecular weight (X(1)) and amount (X(2)); carbopol (X(3)), lactose (X(4)),
      sodium chloride (X(5)), citric acid (X(6)); compression pressure (X(7))--on (1)
      the release of theophylline from hydrophilic matrices, demonstrated by changes in
      dissolution rate, and (2) their impact on the release exponent [n] indicative of
      the drug transport mechanism through the diffusion matrix. This objective was
      accomplished utilizing the Placket-Burman screening design. Theophylline tablets
      were prepared according to a 7-factor-12-run statistical model and subjected to a
      24-h dissolution study in phosphate buffer at pH 7.2. The primary response
      variable, Y(4), was the cumulative percent of theophylline dissolved in 12h. The
      regression equation for the response was Y(4)=66.2167 - 17.5833X(1) - 3.3833X(2) 
      9.366X(3) - 1.1166X(4) - 0.6166X(5) + 2.6X(6) - 2.783X(7). This polynomial model
      was validated by the ANOVA and residual analysis. The results showed that only
      two factors (X(2) and X(3)) had significant effect (p-value<0.10) on theophylline
      release from the hydrophilic polymer matrix. Factors (X(2) and X(7)) had
      significant effect (p-value<0.10) on [n], the exponent.

PMID- 16413979
TI  - Stabilization and encapsulation of a staphylokinase variant (K35R) into
      poly(lactic-co-glycolic acid) microspheres.
AB  - The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA)
      microspheres containing a staphylokinase variant K35R (DGR) with purpose of
      preserving the protein stability during both encapsulation and drug release. DGR
      loaded microspheres are fabricated using a double-emulsion solvent extraction
      technique. Prior to encapsulation, the effect of ultrasonication emulsification
      of DGR solutions with methylene chloride on protein recovery was investigated.
      Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused
      approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR
      solutions significantly improved DGR recovery to >90%. The effects of co
      encapsulated PVA and NaCl in the external aqueous phase on the characteristics of
      the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl
      was added to the external water phase, DGR encapsulation efficiency was
      significantly increased from 7.1% to 78.1% and DGR was distributed uniformly
      throughout the microspheres. In vitro release test showed that DGR was released
      from PLGA microspheres in a sustained manner over 15 days. A large amount of
      released DGR was inactive in the absence of co-encapsulated PVA. On the contrary,
      when 2% PVA was co-encapsulated, the released DGR was almost completely intact
      within 9 days. In conclusion, PLGA microspheres can be an effective carrier for
      DGR and form a promising depot system.

PMID- 16413980
TI  - Lyotropic liquid crystalline phases formed from glycerate surfactants as
      sustained release drug delivery systems.
AB  - A new class of surfactants with glycerate headgroups, that form viscous lyotropic
      liquid crystalline phases in excess water, have been investigated for their
      potential to provide sustained release matrices for depot drug delivery. Oleyl
      glycerate and phytanyl glycerate were used as representative surfactants of this
      new class, and their behaviour compared with that of glyceryl monooleate (GMO).
      The surfactants were found to form reverse hexagonal phase (H(II)) in excess
      water, and the matrices were loaded with a series of model hydrophobic and
      hydrophilic drugs, (paclitaxel, irinotecan, glucose, histidine and octreotide),
      and the release kinetics determined. In all cases, the release behaviour obeyed
      Higuchi kinetics, with linear drug release versus square root of time. The H(II)
      phases released model drugs slower than the GMO cubic phase matrix. The oleyl
      glycerate matrix was found to consistently release drug faster than the phytanyl
      glycerate matrix, despite both matrices being based on H(II) phase. To further
      demonstrate the potential utility of these materials as drug depot delivery
      systems, an injectable precursor formulation for octreotide was also prepared and
      demonstrated to provide controlled release for the peptide. The stability of the
      H(II) phase to likely in vivo breakdown products was also assessed.

PMID- 16413981
TI  - Schwannoma originating from the infraorbital nerve: a case report.
AB  - A 16-year-old female admitted to otolaryngology outpatient clinic with the
      complaints of pain and replacement of her left eyeball upwards. Radiological
      imaging demonstrated a solid mass inferior to the left globe. The anterior wall
      of the maxilla was thinned and the mass pushed the orbital floor inferiorly.
      Following subciliary incision, the bone over the mass was removed from the
      orbital rim and the mass was exposed. The mass originated from the infraorbital
      nerve. The mass was excised and the orbital rim, malar region and the orbital
      floor were reconstructed by a titanium mesh. The histopathological report was
      "schwannoma". Seven cases of schwannomas arising from the infraorbital nerve
      reported in English literature. In this paper we report a case of infraorbital
      schwannoma and review the literature.

PMID- 16413982
TI  - Sudden hearing loss due to meningeal carcinomatosis from rectal carcinoma.
AB  - We present a case of meningeal carcinomatosis with bilateral hearing loss
      secondary to a rectal adenocarcinoma. A 60-year-old woman developed progressive
      loss of hearing in the left ear 19 months after an abdominoperineal resection for
      an adenocarcinoma of the rectum. Three months after the onset of left hearing
      loss, she visited our hospital. Pure tone audiometry revealed profound
      sensorineural hearing loss in the left ear and mild sensorineural hearing loss in
      the right ear. Gadolinium-enhanced MRI revealed tumor in the left internal
      auditory canal and cerebellopontine angle and enhancement in the right internal
      auditory canal. Six days after the first examination, pure tone audiometry
      revealed profound loss of hearing in the right ear. DPOAE of the right ear were
      still detected 6 days after the first examination, but were clearly decreased 9
      days after it, and reached noise level 10 days after it. Gadolinium-enhanced MRI
      revealed rapid growth of the tumor of the right internal auditory canal and
      cerebellopontine angle. We clearly demonstrate here the rapid course of hearing
      loss using pure tone audiometry, MRI, and DPOAE.

PMID- 16413983
TI  - Optimal scanning protocol of multislice CT virtual intravascular endoscopy in pre
      aortic stent grafting: in vitro phantom study.
AB  - OBJECTIVE: To investigate the optimal scanning protocol for multislice computed
      tomography angiography (MSCT) in pre-aortic stent grafting observed with virtual
      intravascular endoscopy (VIE). MATERIALS AND METHODS: The study was performed on
      a human abdominal aortic phantom which was housed in a perspex container, filled
      with contrast medium having CT attenuation similar to that used in the patient's
      abdominal CT scan. A series of scans were performed on a four-slice multislice CT
      scanner with the scanning protocols as follows: section thickness of 1.3, 3.2 and
      6.5 mm, pitch value of 0.875, 1.25 and 1.75 with reconstruction intervals of 50%
      overlap. The degree of stair-step artifacts was measured at three different
      locations, superior mesenteric artery (SMA), renal ostium and the normal
      abdominal aorta. Standard deviation (S.D.) of the signal intensity measured on
      surface shaded images was used to determine the image quality. Radiation dose was
      also recorded in each scanning protocol. RESULTS: The VIE images showed that
      image quality was not dependent on pitch and section thickness in the
      visualization of renal ostium and SMA, whereas it was dependent on these two
      factors at the level of the normal aorta (p<0.05). It was noticed that when
      section thickness reached 6.5 mm the SMA and renal ostia became distorted.
      Radiation dose measured in 1.3 mm protocols was significantly higher that those
      measured in other section thicknesses (p<0.05). CONCLUSION: The scanning protocol
      of section thickness 3.2 mm, pitch 1.25 with a reconstruction interval of 1.6 mm
      was recommended as it allows optimal visualization of VIE images of aortic ostia,
      generation of fewer artifacts and less radiation dose.

PMID- 16413984
TI  - MRI of normal fetal brain development.
AB  - Normal fetal brain maturation can be studied by in vivo magnetic resonance
      imaging (MRI) from the 18th gestational week (GW) to term, and relies primarily
      on T2-weighted and diffusion-weighted (DW) sequences. These maturational changes
      must be interpreted with a knowledge of the histological background and the
      temporal course of the respective developmental steps. In addition, MR
      presentation of developing and transient structures must be considered. Signal
      changes associated with maturational processes can mainly be ascribed to the
      following changes in tissue composition and organization, which occur at the
      histological level: (1) a decrease in water content and increasing cell-density
      can be recognized as a shortening of T1- and T2-relaxation times, leading to
      increased T1-weighted and decreased T2-weighted intensity, respectively; (2) the
      arrangement of microanatomical structures to create a symmetrical or asymmetrical
      environment, leading to structural differences that may be demonstrated by DW
      anisotropy; (3) changes in non-structural qualities, such as the onset of a
      membrane potential in premyelinating axons. The latter process also influences
      the appearance of a structure on DW sequences. Thus, we will review the in vivo
      MR appearance of different maturational states of the fetal brain and relate
      these maturational states to anatomical, histological, and in vitro MRI data.
      Then, the development of the cerebral cortex, white matter, temporal lobe, and
      cerebellum will be reviewed, and the MR appearance of transient structures of the
      fetal brain will be shown. Emphasis will be placed on the appearance of the
      different structures with the various sequences. In addition, the possible
      utility of dynamic fetal sequences in assessing spontaneous fetal movements is
      discussed.

PMID- 16413985
TI  - Post-mortem fetal MRI: what do we learn from it?
AB  - Post-mortem magnetic resonance (MR) imaging is of increasing interest not only as
      an alternative to autopsy but as a research tool to aid the interpretation and
      diagnosis of in utero MR images. The information from the post-mortem MR has
      allowed the development of imaging sequences applicable to in utero imaging and
      neonatal imaging. It has established brain development during gestation and has
      provided data on this to which in utero MR can be compared. The detail available
      from the post-mortem images is such that brain development can be studied in a
      non-invasive manner, a permanent record on the normal and abnormal areas is
      available and a greater understanding of developmental abnormalities is possible.

PMID- 16413986
TI  - Magnetic resonance imaging of the normal placenta.
AB  - The goal of this study was to provide a representative description of the normal
      placenta with contrast medium-free magnetic resonance imaging (MRI) in order to
      determine a standard of reference. One hundred consecutive singleton pregnancies
      were investigated by MRI without application of a contrast medium. The mean
      gestational age (GA) at the time of investigation was 29.5 weeks (range 19-40).
      Patients with suspected utero-placental insufficiency (UPI) or placental
      anomalies were excluded. Signal intensities were assessed and correlated with the
      respective GA. Antenatal MRI without contrast medium was able to depict placental
      status and morphological changes during gestation. A regular homogeneous
      structure was found in weeks 19-23. Subsequently, sporadic, slightly marked
      lobules appeared, which increased in number and markedness with ongoing
      gestation. Stratification of the lobules was observed after 36 weeks. The ratio
      of placental and amniotic fluid signal intensities decreased significantly with
      higher GA and with placental grading. MRI is well suited as an imaging method for
      the placenta. Our data may be used as a reference in the assessment of the
      placenta on MRI, and may have further clinical impact with respect to the
      determination of UPI.

PMID- 16413987
TI  - MRI of normal and pathological fetal lung development.
AB  - Normal fetal lung development is a complex process influenced by mechanical and
      many biochemical factors. In addition to ultrasound, fetal magnetic resonance
      imaging (MRI) constitutes a new method to investigate this process in vivo during
      the second and third trimester. The techniques of MRI volumetry, assessment of
      signal intensities, and MRI spectroscopy of the fetal lung have been used to
      analyze this process and have already been applied clinically to identify
      abnormal fetal lung growth. Particularly in conditions such as oligohydramnios
      and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause
      of neonatal death. A precise diagnosis and quantification of compromised fetal
      lung development may improve post- and perinatal management. The main events in
      fetal lung development are reviewed and MR volumetric data from 106 normal
      fetuses, as well as different examples of pathological lung growth, are provided.

PMID- 16413988
TI  - Liquid chromatographic/mass spectrometry assay of triptolide in dog plasma and
      its application to pharmacokinetic study.
AB  - A rapid and sensitive method for the determination of triptolide in dog plasma
      was developed and validated, using high-performance liquid
      chromatography/atmospheric pressure chemical ionization mass spectrometry
      (LC/APCI/MS). Sample preparation consisted of liquid-liquid extraction with ethyl
      acetate from dog plasma. The analytes and internal standard prednisolone were
      well separated on a Zorbax Extend-C18 analytical column. Detection was performed
      on a triple quadrupole mass spectrometer using selected-ion monitoring (SIM) mode
      on the deprotonated ions [M-H]- at m/z 359. Calibration curves were linear over
      the concentration range of 0.5-200 ng/mL of triptolide with the intra- and inter
      day precision (the relative standard deviation values) were being less than 7%.
      Triptolide was stable under different conditions. The intra-day and inter-day
      accuracy were 99.3-105.2% and 101.3-107.0%, respectively. The lower limit of
      quantification was 0.5 ng/mL. The method was successfully applied to a
      pharmacokinetic study after an intragastric administration (i.g.) of triptolide
      to dogs with a dose of 0.05 mg/kg. The results confirm that the assay is suitable
      for the pharmacokinetic study of triptolide.

PMID- 16413989
TI  - Potential role of NF-kappaB in adult neural stem cells: the underrated steersman?
AB  - Neural stem cells are precursors of neurons and glial cells. During brain
      development, these cells proliferate, migrate and differentiate into specific
      lineages. Recently neural stem cells within the adult central nervous system were
      identified. Informations are now emerging about regulation of stem cell
      proliferation, migration and differentiation by numerous soluble factors such as
      chemokines and cytokines. However, the signal transduction mechanisms downstream
      of these factors are less clear. Here, we review potential evidences for a novel
      central role of the transcription factor nuclear factor kappa B (NF-kappaB) in
      these crucial signal transduction processes. NF-kappaB is an inducible
      transcription factor detected in neurons, glia and neural stem cells. NF-kappaB
      was discovered by David Baltimore's laboratory as a transcription factor in
      lymphocytes. NF-kappaB is involved in many biological processes such as
      inflammation and innate immunity, development, apoptosis and anti-apoptosis. It
      has been recently shown that members of the NF-kappaB family are widely expressed
      by neurons, glia and neural stem cells. In the nervous system, NF-kappaB plays a
      crucial role in neuronal plasticity, learning, memory consolidation,
      neuroprotection and neurodegeneration. Recent data suggest an important role of
      NF-kappaB on proliferation, migration and differentiation of neural stem cells.
      NF-kappaB is composed of three subunits: two DNA-binding and one inhibitory
      subunit. Activation of NF-kappaB takes place in the cytoplasm and results in
      degradation of the inhibitory subunit, thus enabling the nuclear import of the
      DNA-binding subunits. Within the nucleus, several target genes could be
      activated. In this review, we suggest a model explaining the multiple action of
      NF-kappaB on neural stem cells. Furthermore, we discuss the potential role of NF
      kappaB within the so-called brain cancer stem cells.

PMID- 16413990
TI  - Natural variation of ascospore and conidial germination by Fusarium
      verticillioides and other Fusarium species.
AB  - Fusarium verticillioides and other Fusarium species were examined for their spore
      germination phenotypes. In general, germinating spores of F. verticillioides
      formed germ tubes that immediately penetrated into agar. Such invasive
      germination was the predominant growth phenotype among 22 examined field isolates
      of F. verticillioides from a broad range hosts and locations. However, two of the
      field isolates were unique in that they formed conidial germ tubes and hyphae
      that grew along the surface of agar before penetration eventually occurred.
      Conidia of 22 other Fusarium species were assessed for their germination
      phenotypes, and only some strains of F. annulatum, F. fujikuroi, F. globosum, F.
      nygamai, and F. pseudoanthophilum had the surface germination phenotype (21% of
      the strains assessed). Sexual crosses and segregation analyses involving one of
      the F. verticillioides surface germination strains, NRRL 25059, indicated a
      single locus, designated SIG1 (surface vs. invasive germination), controlled the
      germ tube growth phenotypes exhibited by both conidia and ascospores. Perfect
      correlation was observed between an ascospore germination phenotype and the
      germination phenotype of the conidia produced from the resulting ascospore
      derived colony. Recombination data suggested SIG1 was linked ( approximately 7%
      recombination frequency) to FPH1, a recently described locus necessary for
      enteroblastic conidiogenesis. Corn seedling blight assays indicated surface
      germinating strains of F. verticillioides were less virulent than invasively
      germinating strains. Assays also indicated pathogenicity segregated independently
      of the FPH1 locus. Invasive germination is proposed as the dominant form of spore
      germination among Fusarium species. Furthermore, conidia were not necessary for
      corn seedling disease development, but invasive germination may have enhanced the
      virulence of conidiating strains.

PMID- 16413991
TI  - Activation of kinase pathways in MCF-7 cells by 17beta-estradiol and structurally
      diverse estrogenic compounds.
AB  - 17beta-Estradiol (E2) activates non-genomic pathways in MCF-7 cells, and this
      study investigates the effects of structurally-diverse estrogenic compounds on
      activation of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3
      kinase (PI3-K), protein kinase C (PKC), PKA, and calcium calmodulin-dependent
      kinase IV (CaMKIV). Activation of kinases was determined by specific substrate
      phosphorylation and transactivation assays that were diagnostic for individual
      kinases. The compounds investigated in this study include E2, diethylstilbestrol
      (DES), the phytoestrogen resveratrol, and the following synthetic xenoestrogens,
      bisphenol-A (BPA), nonylphenol, octylphenol, endosulfan, kepone, 2,2-bis(p
      hydroxyphenyl)-1,1,1-trichloroethane (HPTE), and 2',3',4',5'-tetrachloro-4
      biphenylol (HO-PCB-Cl(4)). With the exception of resveratrol, all the compounds
      activated PI3-K and MAPK. Activation of PKC by the xenoestrogens was structure
      dependent since resveratrol, kepone and HO-PCB-Cl(4) were inactive and only
      minimal activation of PKA was observed. CaMKIV was activated only by E2 and DES,
      and HO-PCB-Cl(4) was a potent inhibitor of CaMKIV-dependent activity. These
      results demonstrate that activation of estrogen receptor-alpha-mediated non
      genomic pathways by estrogenic compounds in MCF-7 cells is structure-dependent
      and can result in activation or inhibition of kinase activities.

PMID- 16413992
TI  - A theoretical model evaluating the angular distribution of luminescence emission
      in X-ray scintillating screens.
AB  - The aim of this study was to examine the angular distribution of the light
      emitted from radiation-excited scintillators in medical imaging detectors. This
      distribution diverges from Lambert's cosine law and affects the light emission
      efficiency of scintillators, hence it also affects the dose burden to the
      patient. In the present study, the angular distribution was theoretically modeled
      and was used to fit experimental data on various scintillator materials. Results
      of calculations revealed that the angular distribution is more directional than
      that predicted by Lambert's law. Divergence from this law is more pronounced for
      high values of light attenuation coefficient and thick scintillator layers
      (screens). This type of divergence reduces light emission efficiency and hence it
      increases the incident X-ray flux required for a given level of image brightness.

PMID- 16413993
TI  - Pregabalin: a new antiepileptic drug for refractory epilepsy.
AB  - Pregabalin is a recently licensed and marketed antiepileptic drug for use as
      adjunctive treatment of partial epilepsy. It acts at presynaptic calcium
      channels, modulating neurotransmitter release in the CNS, properties it shares
      with gabapentin. Its clinical development over the past decade has included its
      use in the treatment of neuropathic pain, and generalized anxiety disorder, in
      addition to epilepsy. Three multi-centre randomised, double-blind, placebo
      controlled trials enrolling patients with refractory partial epilepsy have
      demonstrated an antiepileptic effect of pregabalin against placebo, as adjunctive
      therapy, with 31-51% of patients showing a 50% reduction in seizure frequency.
      Adverse effects were dose related, the commonest being somnolence, dizziness, and
      ataxia. Weight gain was seen in 14% of patients on the highest dose of 600
      mg/day. Around 9000 people have been exposed to pregabalin in its development for
      all indications. No idiosyncratic reactions have been described to date.
      Pregabalin may be a useful addition in the treatment of refractory partial
      epilepsy. As with all new AEDs long-term follow up and post marketing
      surveillance is required.

PMID- 16413994
TI  - Long-term treatment with theophylline reduces neutrophils, interleukin-8 and
      tumor necrosis factor-alpha in the sputum of patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: The non-selective phosphodiesterase inhibitor theophylline has
      bronchodilator/anti-inflammatory properties and is widely used in the treatment
      of airways diseases. We determined the effect of long-term theophylline treatment
      on airway inflammation in patients with chronic obstructive pulmonary disease
      (COPD). POPULATIONS AND METHODS: Seventeen stable COPD patients were enrolled in
      the 12-month study. Theophylline was administered at 400mg/day. We studied
      changes in symptoms, spirometry, sputum volume, and sputum inflammatory cytokines
      levels. We also examined the effects of theophylline on the release of
      inflammatory cytokines in vitro by measuring interleukin (IL)-8 and tumor
      necrosis factor (TNF)-alpha levels from lipopolysaccharide (LPS)-stimulated
      neutrophils and THP-1 cells. RESULTS: Forced vital capacity was increased and
      sputum IL-8 levels decreased after 4 weeks of theophylline treatment. After 6
      months of theophylline treatment, forced expiratory volume in 1s was increased,
      and neutrophils counts and TNF-alpha levels in sputum were reduced. Levels of IL
      8 and TNF-alpha released by LPS-stimulated THP-1 cells were reduced by treatment
      with theophylline at 10microg/ml. In contrast, IL-8 levels released by LPS
      stimulated neutrophils were reduced by treatment with theophylline at
      100microg/ml. CONCLUSION: Our clinical study of small population showed that long
      term treatment with theophylline seems to reduce airway inflammation in stable
      COPD patients.

PMID- 16413995
TI  - Sonocatalytic degradation of methyl parathion in the presence of nanometer and
      ordinary anatase titanium dioxide catalysts and comparison of their sonocatalytic
      abilities.
AB  - The degradation of methyl parathion (O,O-dimethyl-O-(4-nitrophenyl)
      phosphorothioate) using anatase titanium dioxide (TiO(2)) powder as heterogeneous
      sonocatalysts is reported. The influences of reaction parameters such as the
      species of TiO(2) sonocatalysts, methyl parathion concentrations, TiO(2) adding
      amount, pH, ultrasonic intensity, ultrasonic frequency and temperature have been
      investigated and the optimal conditions for eliminating methyl parathion have
      been identified. The efficiencies of sonocatalytic degradation in both nanometer
      and ordinary anatase systems are compared and the results indicate that the
      sonocatalytic activity of nanometer anatase TiO(2) powder is better than that of
      ordinary anatase TiO(2) powder. The primary degradation and the total
      mineralization of methyl parathion have been monitored by high performance liquid
      chromatography (HPLC) and UV-vis spectra, respectively. Methyl parathion got
      destroyed to some extent in both nanometer and ordinary anatase systems under
      ultrasonic irradiation. The kinetics for the degradation process of methyl
      parathion follows the first-order reaction. The degradation ratio of methyl
      parathion surpassed 90% within 50min in the optimal experiment conditions.

PMID- 16413996
TI  - Ultrasonic damages on cyanobacterial photosynthesis.
AB  - Excessive cyanobacterial growth in eutrophic water sources has been a serious
      environmental problem, and both sight preservation and drinking water production
      demand control of cyanobacterial growth in water. Ultrasonic treatment was
      reported to effectively inhibit cyanobacterial growth through vesicle collapsing
      and cell fracturing, but little was known about the change of cyanobacterial
      photosynthesis during sonication. This paper examined the ultrasonic inhibition
      of Microcystis aeruginosa cell growth and extracellular microcystins release, and
      the instant ultrasonic decreases of antenna complexes like cyanobacterial
      chlorophyll a and phycocyanins (PC), and the oxygen evolution rate. The results
      showed that sonication effectively damaged antenna complexes, slowed down the
      photo-activity, which significantly inhibited the cell growth and microcystins
      formation and release.

PMID- 16413997
TI  - Geohelminth infections: impact on allergic diseases.
AB  - Geohelminth infections are highly prevalent infections with a worldwide
      distribution. Epidemiological studies have shown an inverse relationship between
      geohelminth infection and allergy leading to the suggestion that geohelminths
      protect against allergy. A causal association is supported by the findings of
      intervention studies in humans and experimental animal models. Geohelminths cause
      chronic infections during which an intimate host-parasite interaction develops
      permitting the parasite to survive but protecting the host from damaging
      inflammation. Geohelminth parasites modulate allergic inflammation directed
      against parasite antigens and the same mechanisms may affect responses to
      inhalant aeroallergens. The mechanisms proposed to explain the allergy-modulatory
      effect of geohelminths include the induction of regulatory T cells and the
      creation of an immunosuppressive environment in relevant tissues. New treatments
      being considered for the treatment of asthma include live infections with
      hookworms. Insights provided by how geohelminths modulate inflammatory responses
      may allow the development of new treatments that mimic these effects.

PMID- 16413998
TI  - Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS
      1E cells.
AB  - PDZD2 (PDZ domain containing 2) is a multi-PDZ protein expressed in pancreas and
      many other tissues. PDZD2 shows extensive homology to pro-interleukin-16 (pro-IL
      16) and is localized mainly to the endoplasmic reticulum. We have recently
      demonstrated that PDZD2, like pro-IL-16, is proteolytically cleaved at its C
      terminus to generate a secreted protein, sPDZD2 (for secreted PDZD2). To
      understand the possible functional role of PDZD2 in pancreas, we investigated the
      cellular distribution of PDZD2 in adult pancreas using an antiserum that
      recognizes both the full-length and secreted forms of PDZD2. Immunohistochemical
      analysis revealed a strong expression of PDZD2 in pancreatic islet beta cells but
      not alpha cells. Consistent with the beta-cell-enriched expression of PDZD2,
      immunoblot analysis indicated expression of both full-length PDZD2 and sPDZD2 in
      the insulinoma cell line INS-1E. A recombinant sPDZD2 protein was synthesized for
      study of its functional effect on INS-1E cells. In culture media with limiting
      serum, co-incubation with sPDZD2 stimulated the proliferation of INS-1E cells.
      The mitogenic effect of sPDZD2 was concentration-dependent, and was associated
      with a slight inhibition of the insulin promoter activity at high sPDZD2
      concentrations. As a potential mitogen of beta-like cells, sPDZD2 may be useful
      for the optimization of beta-cell growth and differentiation in vitro.

PMID- 16413999
TI  - The level of endothelin-1 and nitric oxide in patients with chronic viral
      hepatitis B and C and correlation with histopathological grading and staging.
AB  - BACKGROUND AND AIM: The aim of this study was to estimate the serum levels of
      endothelin-1 (ET-1) and nitric oxide (NO) and to analyze the correlation of their
      levels with histopathological grading and staging of the liver in patients with
      chronic hepatitis B (CHB) and C (CHC). METHODS: Eighty-nine patients who were
      either HBsAg positive (45 CHB patients, 34 inactive carriers (IC)) or had CHC (10
      patients) and 36 healthy volunteers as a control group were included in this
      study. Fifty patients from the CHB (n=43) or CHC (n=7) groups with elevated serum
      alanine transaminase (ALT) levels underwent a liver biopsy. Histological activity
      was scored according to Ishak's activity and the fibrotic index. The ET-1 serum
      concentration was determined with a commercially available ELISA assay kit. Total
      nitrite was measured by the Griess reaction as an index for NO production.
      RESULTS: Serum levels of ET-1 and NO were significantly increased in CHB patients
      (7.67+/-4.00pg/ml and 172.44+/-50.30mumol/l, respectively) compared with the IC
      group (3.99+/-5.42pg/ml and 114.68+/-32.22mumol/l, respectively) and the control
      group (3.05+/-0.65pg/ml and 58.61+/-24.18mumol/l, respectively) (p<0.0001). The
      CHC patients also had significantly higher serum levels of ET-1 (5.92+/
      4.24pg/ml) and NO (147.50+/-55.84mumol/l) compared to the control group (p<0.0001
      and <0.001, respectively). Linear regression analysis identified that the level
      of ET-1 was an independent variable that correlated significantly with the stage
      score (r(2)=0.348, p<0.0001) in CHB patients but there was no correlation in the
      CHC group. CONCLUSION: ET-1 and NO levels were increased in chronic hepatitis and
      there was a significant correlation between the ET-1 level and the stage in CHB
      patients.

PMID- 16414000
TI  - Magnetoencephalography in healthy neonates.
AB  - OBJECTIVE: To describe magnetoencephalography (MEG) recordings in a cohort of
      healthy neonates. METHODS: We performed MEG and single channel EEG concomitantly
      in 21 healthy newborns. MEG and EEG signals were reviewed for gross comparison of
      general patterns and individual waveform characteristics. Spectral analysis was
      performed to quantify the signals. RESULTS: Our MEG recordings showed patterns
      comparable to classical neonatal EEG. Seventy-nine percent of the subjects
      exhibited the 'continuous polyfrequency activity' at some point in their
      recording. Sixty-three percent had the 'continuous slow' pattern, and 47% had the
      'trace alternant' pattern. Spectral analysis revealed maximal power at
      frequencies of less than 4 Hz (delta band) in both MEG and EEG with a decline
      towards higher frequencies. CONCLUSIONS: Neonatal MEG is feasible and shares the
      basic EEG features and frequency content, with predominant activity in the slow
      frequency delta band. The latter corresponds to reports from earlier neonatal EEG
      studies. SIGNIFICANCE: MEG may prove to be useful in studies of neonatal brain
      functions.

PMID- 16414001
TI  - Sympathetic skin response in patients with peripheral arterial occlusive disease.
AB  - OBJECTIVE: The current study aimed to assess the viability of sympathetic
      sudomotor fibers in patients suffering from mild peripheral arterial occlusive
      disease (PAD). METHODS: Sympathetic skin response (SSR) from the hand (electrical
      stimulation) and sole (electrical and magnetic stimulation) of 25 patients with
      PAD (19 males and 6 females with mean age 62.7 +/- 10.2 years) was recorded
      unilaterally depending on the side of the affected limb (18 right side, 7 left
      side). Electrophysiological data were also collected and correlated with the SSR
      results. Twenty-five, age- and gender-matched healthy volunteers served as
      controls. RESULTS: No evidence of nerve conduction abnormalities was recorded
      from the group of patients. Intact SSR recordings were obtained from the upper
      limb of patients. Nine patients (36%) had absent SSR in the lower limb following
      electrical stimulation, whilst the same 9 patients had absent SSR following
      magnetic stimulation. Significant differences occurred between groups in the SSR
      latency scores recorded from the lower limb. Following electrical stimulation the
      mean SSR latency in patients was significantly prolonged, compared to that of
      controls (P = 0.000), whilst the same applied following magnetic stimulation (P =
      0.000). There was no correlation between SSR abnormalities and nerve conduction
      measurements. The manifestation of intermittent claudication at a walking
      distance of 250 m was strongly correlated with absent lower limb SSR (r = 0.71, P
      = 0.035). CONCLUSIONS: SSR abnormalities appeared to be an early and independent
      finding of neural impairment in our patients. SIGNIFICANCE: SSR study, performed
      at an early stage of PAD may prove useful in differentiating PAD-induced
      neuropathy from other neuropathic processes.

PMID- 16414002
TI  - Development of MEG sleep patterns and magnetic auditory evoked responses during
      early infancy.
AB  - OBJECTIVE: To follow the development of MEG sleep patterns and auditory evoked
      responses (AERs) during the first six months of life. METHODS: The subjects were
      18 neonates, born at conceptional age (CA) 36-42 weeks, following uncomplicated
      pregnancies. During each session, several 10-min MEG recordings were acquired in
      the presence of auditory stimulation. The recordings were classified into three
      distinct MEG patterns-low amplitude irregular; high-amplitude slow; and mixed
      based largely on MEG amplitude and frequency. Averaged AERs were computed for the
      entire recording and for each MEG pattern within the recording. The results were
      based on analysis of 61 recording sessions of the 10 subjects who yielded three
      or more sessions of usable data. RESULTS: Developmental changes in the MEG sleep
      patterns were most pronounced at the earliest ages. By CA 48 weeks the patterns
      had progressed to a more mature form, characterized by the prevalence of delta
      wave sleep, absence of discontinuity, and development of spindling and higher
      amplitude delta rhythms. In contrast to the MEG patterns, the AERs did not change
      markedly during the first 8 weeks (CA 40-48 weeks) and showed a simple
      morphology, consisting of a prominent deflection at 250 ms (P250m) and a more
      diffuse one at around 750 ms (N750m). During the period CA 48-54 weeks, however,
      a relatively abrupt transition occurred to a more complex morphology,
      characterized by a double peak with peak latencies 150ms (P150m) and 350 ms
      (P350m). Beyond this period the AERs continued to evolve, showing biphasic
      complexes and the emergence of late components arising from outside the auditory
      cortex. CONCLUSIONS: Over the age range of this study the MEG sleep patterns and
      AER developed in succession, rather than concurrently; i.e. development of the
      sleep patterns was most rapid during the first 8 weeks (CA 40-48 weeks) while
      major development of the AERs commenced after this time. SIGNIFICANCE: This
      finding suggests that the brain must achieve a certain level of overall maturity,
      reflected in the character of the MEG sleep patterns at CA 48 weeks, before the
      cortex enters a phase of significant functional development, reflected in the
      more rapid evolution of the AER after CA 48 weeks. The results of this study
      affirm the efficacy of MEG for spatiotemporal characterization of neonatal brain
      activity.

PMID- 16414003
TI  - Temporal transferability and updating of zonal level accident prediction models.
AB  - This paper examines the temporal transferability of the zonal accident prediction
      models by using appropriate evaluation measures of predictive performance to
      assess whether the relationship between the dependent and independent variables
      holds reasonably well across time. The two temporal contexts are the years 1996
      and 2001, with updated 1996 models being used to predict 2001 accidents in each
      traffic zone of the City of Toronto. The paper examines alternative updating
      methods for temporal transfer by imagining that only a sample of 2001 data is
      available. The sensitivity of the performance of the updated models to the 2001
      sample size is explored. The updating procedures examined include the Bayesian
      updating approach and the application of calibration factors to the 1996 models.
      Models calibrated for the 2001 samples were also explored, but were found to be
      inadequate. The results show that the models are not transferable in a strict
      statistical sense. However, relative measures of transferability indicate that
      the transferred models yield useful information in the application context. Also,
      it is concluded that the updated accident models using the calibration factors
      produce better results for predicting the number of accidents in the year 2001
      than using the Bayesian approach.

PMID- 16414004
TI  - Development of letter-specific processing: the effect of reading ability.
AB  - During development, perceptual processing is tuned to inputs in the environment
      such that certain frequently encountered classes of stimuli are processed more
      effectively than similar comparison stimuli. Letters represent a class of stimuli
      that are encountered frequently in the environment, at least in literate
      cultures. Thus, the present study examined the development of letter-specific
      processing in children 6-19 years old by comparing the difference between
      performance on a letter-matching task and an unfamiliar non-letter-matching task
      in different subject groups. Results revealed an increase in letter-specific
      processing with development. Moreover, comparisons of letter-specific processing
      in groups of subjects matched either in age or reading ability indicate that the
      emergence of letter-specific processing is linked to increased reading skill,
      rather than increased age per se. Findings support theories of perceptual
      expertise, which suggest that skilled processing drives the specialization of
      perceptual mechanisms for certain classes of stimuli.

PMID- 16414005
TI  - A hospital-based retrospective survey of human cystic and alveolar echinococcosis
      in Ningxia Hui Autonomous Region, PR China.
AB  - A retrospective study of in-patient records for the period 1985-2001 collected
      from 11 hospitals in Ningxia Hui Autonomous Region (NHAR), China revealed a total
      of 2216 cases of echinococcosis. The survey showed that cystic echinococcosis
      (CE) occurs throughout NHAR but that human alveolar echinococcosis (AE) cases
      were only located in a confluence area of three counties, Xiji, Haiyuan and
      Guyuan. Incidence rates between counties within southern NHAR showed a highly
      heterogeneous distribution of cases, suggestive of different echinococcal
      transmission patterns. There was a significant difference in incidence between
      males and females, and farm labourers accounted for the majority of cases.
      Radical surgery with or without albendazole/mebendazole drug treatment was the
      major method of treatment for CE and repeat surgery was common; drug treatment
      alone was used mainly for AE. Epigastric pain was the main reason for patients
      seeking medical advice, the liver was the primary location of echinococcosis
      lesions and the majority of echinococcosis cases were diagnosed by ultrasound.
      Over a 12 year period, the average bed utilization rate in the Second Provincial
      Hospital of NHAR for patients with echinococcosis was 78% and echinococcosis
      cases accounted, on average, for 0.7% among the total hospital in-patients.
      Taking inflation into account, charges for echinococcosis hospitalization and
      treatment increased three-fold over the period 1994-2002. This study indicates
      that echinococcosisis is a significant public health problem in NHAR, especially
      in the south. The data from the hospital retrospective study are clearly
      underestimates and community surveys are required to determine the true
      echinococcosis prevalence levels, especially in the more remote areas of NHAR.

PMID- 16414007
TI  - Et tu, Grotthuss! and other unfinished stories.
AB  - This review article is divided into three sections. In Section 1, a short
      biographical note on Freiherr von Grotthuss is followed by a detailed summary of
      the main findings and ideas present in his 1806 paper. Attempts to place
      Grotthuss contribution in the context of the science done at his time were also
      made. In Section 2, the modern version of the Grotthuss mechanism is reviewed.
      The classical Grotthuss model has been recently questioned and new mechanisms and
      ideas regarding proton transfer are briefly discussed. The last section discusses
      the significance of a classical Grotthuss mechanism for proton transfer in water
      chains inside protein cavities. This has been an interesting new twist in the
      ongoing history of the Grotthuss mechanism. A summary and discussion of what was
      learned from probably the simplest currently available experimental models of
      proton transfer in water wires in semi-synthetic ion channels are critically
      presented. This review ends discussing some of the questions that need to be
      addressed in the near future.

PMID- 16414006
TI  - The epidemiology of human trichinellosis in China during 2000-2003.
AB  - The endemic foci of trichinellosis continue to be mainly located in the
      southwestern, the central and northeastern China. The seroepidemiological surveys
      of T. spiralis infection in humans were carried out in six Provinces or
      Municipals (P/M) of China during 2000-2003, the overall seroprevalence was 3.57%.
      From 2000 to 2003, 17 outbreaks of human trichinellosis, with 828 cases and 11
      deaths, were recorded in 8 P/A of China. All of 11 deaths occurred in the
      southwestern China (1 case in Sichuan, 4 cases in Tibet and 6 cases in Yunnan),
      where the ethnic groups have the habit of eating raw meat. Pork is the
      predominant source of outbreaks of human trichinellosis in China. Out of 17
      outbreaks, 13 (76.47%) outbreaks were caused by eating raw or poorly cooked pork,
      2 (11.77%) outbreaks caused by eating raw dog meat and 2 (11.77%) outbreaks by
      eating game meat (wild boar and bear), suggesting the increasing significance of
      dog and game meat as source of infection for human trichinellosis. The partial
      effects of health education interventions for control of trichinellosis have been
      achieved in some counties of Yunnan province. The number of inhabitants eating
      raw meat has decreased from 72.74% (1561/2146) before interventions to 47.43%
      (489/1031) after interventions. The decrease of incidence of trichinellosis in
      China during the past 4 years was probably due to a combination of factors,
      including the reduction in the prevalence of Trichinella infection in domestic
      swine, the strengthened meat inspection, the increased use of home freezers and
      the development of heath education practice.

PMID- 16414008
TI  - Intrinsic ionic conductances mediate the spontaneous electrical activity of
      cultured mouse myotubes.
AB  - Mouse skeletal myotubes differentiated in vitro exhibited spontaneous
      contractions associated with electrical activity. The ionic conductances
      responsible for the origin and modulation of the spontaneous activity were
      examined using the whole-cell patch-clamp technique and measuring [Ca(2+)](i)
      transients with the Ca(2+) indicator, fura 2-AM. Regular spontaneous activity was
      characterized by single TTX-sensitive action potentials, followed by transient
      increases in [Ca(2+)](i). Since the bath-application of Cd(2+) (300 microM) or
      Ni(2+) (50 muM) abolished the cell firing, T-type (I(Ca,T)) and L-type (I(Ca,L))
      Ca(2+) currents were investigated in spontaneously contracting myotubes. The low
      activation threshold (around -60 mV) and the high density of I(Ca,T) observed in
      contracting myotubes suggested that I(Ca,T) initiated action potential firing, by
      bringing cells to the firing threshold. The results also suggested that the
      activity of I(Ca,L) could sustain the [Ca(2+)](i) transients associated with the
      action potential, leading to the activation of apamin-sensitive SK-type Ca(2+)
      activated K(+) channels and the afterhyperpolarization (AHP) following single
      spikes. In conclusion, an interplay between voltage-dependent inward (Na(+) and
      Ca(2+)) and outward (SK) conductances is proposed to mediate the spontaneous
      pacemaker activity in cultured muscle myotubes during the process of myogenesis.

PMID- 16414010
TI  - Polymorphic and differential expression of the Trypanosoma cruzi alleles
      containing universal minicircle binding protein.
AB  - DNA replication mechanisms are poorly understood in most of trypanosomatids, in
      particular the replication of the peculiar mitochondrial DNA, the kinetoplast DNA
      (kDNA). To contribute to the knowledge on the mechanism of kDNA replication in
      Trypanosoma cruzi, we have previously characterized the Universal Minicircle
      Sequence Binding Protein of this parasite (TcUMSBP), which was first called PDZ5
      [E.R. Coelho, T.P. Urmenyi, J. Franco da Silveira, E. Rondinelli, R. Silva,
      Identification of PDZ5, a candidate universal minicircle sequence binding protein
      of Trypanosoma cruzi, Int. J. Parasitol. 33 (2003) 853-858]. In this work, we
      describe two highly polymorphic alleles of the TcUMSBP locus in the T. cruzi
      reference clone CL Brener and the differential expression pattern of these
      alleles. A 62 bp sequence in the TcUMSBP upstream intergenic region in one of its
      alleles affects the efficiency of polycistronic RNA processing and the
      polyadenylation sites, and therefore regulates the differential expression of
      TcUMSBP alleles of this locus.

PMID- 16414009
TI  - Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal
      growth factor receptor transactivation by X-irradiation.
AB  - Exposure of MDA-MB-468 cells to ionizing radiation (IR) caused biphasic
      activation of ERK as indicated by its phosphorylation at Thr202/Tyr204. Specific
      epidermal growth factor receptor (EGFR) inhibitor AG1478 and specific Src
      inhibitor PP2 inhibited IR-induced ERK1/2 activation but phosphatidylinositol-3
      kinase inhibitor wortmannin did not. IR caused EGFR tyrosine phosphorylation,
      whereas it did not induce EGFR autophosphorylation at Tyr992, Tyr1045, and
      Tyr1068 or Src-dependent EGFR phosphorylation at Tyr845. SHP-2, which positively
      regulates EGFR/Ras/ERK signaling cascade, became activated by IR as indicated by
      its phosphorylation at Tyr542. This activation was inhibited by PP2 not by
      AG1478, which suggests Src-dependent activation of SHP-2. Src and PTPalpha, which
      positively regulates Src, became activated as indicated by phosphorylation at
      Tyr416 and Tyr789, respectively. These data suggest that IR-induced ERK1/2
      activation involves EGFR through a Src-dependent pathway that is distinct from
      EGFR ligand activation.

PMID- 16414011
TI  - Near-infrared spectroscopy: promising diagnostic tool for viral infections.
AB  - Although several methods, including enzyme-linked immunosorbent assay, polymerase
      chain reaction, immunofluorescent assay, and Western blotting, have been used for
      the diagnosis of viral infections, none of them is ideal in terms of cost
      effectiveness, speed, and accuracy. Currently, the rate of outbreak of emerging
      viruses is increasing and therefore the development and establishment of
      analytical methods for such viral infections are becoming more important. Near
      infrared (NIR) spectroscopy is a fast, multicomponent assay that enables non
      invasive, non-destructive analysis. Recently, the diagnosis of viral infections
      using NIR spectroscopy has been attempted. In this review, the potential of the
      NIR method in the medical and virological fields is discussed.

PMID- 16414012
TI  - Stage dependent and androgen inductive expression of orphan receptor TR4 in rat
      testis.
AB  - In this study, we investigated the expression of TR4 in different stages of
      seminiferous tubules and the relationship between TR4 and androgen in rat testis.
      We found that TR4 was stage-dependently expressed in rat seminiferous tubules, T
      withdrawal induced by high doses of testosterone undecanoate and ethane dimethane
      sulfonate inhibit TR4 expression in rat testis, and testosterone induced TR4
      expression in co-cultured primary germ/Sertoli cells. Furthermore, we
      demonstrated that androgen receptor could enhance TR4-mediated transactivation
      activity in testis cells in the presence of testosterone. Together, these data
      indicate that the expression of TR4 in rat testis is stage dependent and androgen
      inductive, and suggest the important role of orphan receptor TR4 in
      spermatogenesis.

PMID- 16414013
TI  - In vitro mapping of calnexin interaction with ribosomes.
AB  - Calnexin is an endoplasmic reticulum (ER) resident type I integral membrane
      phosphoprotein. This protein is actively involved in the ER glycoprotein quality
      control through its luminal domain. In addition, although calnexin also interacts
      with membrane-bound ribosomes, the nature of this interaction remains poorly
      characterized. Herein, using in vitro approaches, we demonstrate that calnexin
      cytosolic domain directly interacts with, at least 5 ribosomal proteins.
      Furthermore, we characterize more specifically its interaction with the ribosomal
      protein L4 and that L4 binds to the 19 carboxy terminal amino acids of calnexin.
      We suggest that the direct interaction of calnexin with membrane-bound ribosomes
      may represent a regulatory mechanism for its lectin-like chaperone function.

PMID- 16414014
TI  - Osteopontin: a rapid and sensitive response to dioxin exposure in the
      osteoblastic cell line UMR-106.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting
      environmental pollutant that, among other effects, affects bone tissue. TCDD
      modulates the transcription of various genes, e.g., CYP1A1, and the present study
      is a part of a project aiming at developing an in vitro model system for
      identifying biomarkers specific for dioxin-induced effects in osteoblasts.
      Osteopontin (OPN) is an adhesion protein, suggested to be important in bone
      remodeling and our results indicate that TCDD down-regulates the transcription of
      OPN in the osteoblastic cell line, UMR-106. The present study shows that UMR-106
      expresses the AhR and that the expression of CYP1A1 is induced after exposure to
      TCDD, while down-regulation of OPN is an even more rapid response and a sensitive
      biomarker to TCDD exposure in this osteoblastic cell line. In conclusion, this
      osteoblastic cell line may be used as an in vitro model-system for studying
      dioxin-induced effects on osteoblasts.

PMID- 16414015
TI  - Impaired expression of importin/karyopherin beta1 leads to post-implantation
      lethality.
AB  - Importin beta1 (Impbeta)/karyopherin beta1 (Kpnb1) mediates the nuclear import of
      a large variety of substrates. This study aimed to investigate the requirement
      for the Kpnb1 gene in mouse development, using a gene trap line, B6-CB
      Ayu8108(GtgeoIMEG) (Ayu8108(geo)), in which the trap vector was inserted into the
      promoter region of the Kpnb1 gene, but in reverse orientation of the Kpnb1 gene.
      Ayu8108(geo/geo) homozygous embryos could develop to the blastocyst stage, but
      died before embryonic day 5.5, and expression of the Kpnb1 gene in homozygous
      blastocysts was undetectable. We also replaced the betageo gene with Impbeta cDNA
      through Cre-mediated recombination to rescue Impbeta expression. Homozygous mice
      for the rescued allele Ayu8108(Impbeta/Impbeta) were born and developed normally.
      These results demonstrated that the cause of post-implantation lethality of
      Ayu8108(geo/geo) homozygous embryos was impaired expression of the Kpnb1 gene,
      indicating indispensable roles of Impbeta1 in early development of mice.

PMID- 16414016
TI  - Velocity of polymer translocation through a pore.
AB  - We theoretically study the translocation time and the mean velocity of a long
      polymer threading a long nanopore on an external electric field. Theoretical
      method, which explicitly takes into account the nucleation theory, is presented
      based on the built polymer expanded model. We overcame the previous theory's
      defect which did not consider the real length of the pore. The present model
      implies that the length scale of a pore plays a very important role in the
      process of polymer translocation. Our calculation results are in agreement with
      those of previous experiments.

PMID- 16414017
TI  - Identification of the functional domains of ANT-1, a novel coactivator of the
      androgen receptor.
AB  - Previously, we identified a transcriptional coactivator for the activation
      function-1 (AF-1) domain of the human androgen receptor (AR) and designated it
      androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This
      coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from
      amino acid (aa) 294, is identical to a component of U5 small nuclear
      ribonucleoprotein particles and binds specifically to the AR or glucocorticoid
      receptor. Here, we identified four distinct functional domains. The AR-AF-1
      binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly
      overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation
      domain in ANT-1 were assigned within the TPR motifs, while the transactivating
      and nuclear localization signal domains resided within the N-terminal sequence.
      The existence of these functional domains may further support the idea that ANT-1
      can function as an AR-AF-1-specific coactivator while mediating a transcription
      splicing coupling.

PMID- 16414018
TI  - Changes of skeletal muscle adiponectin content in diet-induced insulin resistant
      rats.
AB  - The current study examined the relationship between skeletal muscle levels of
      adiponectin and parameters of insulin sensitivity. A high fat/sucrose diet (HFD)
      for 20 weeks resulted in significant increases in body weight, serum insulin,
      triglycerides (TG), and free fatty acids (FFA) (all p < 0.01). Interestingly,
      this diet leads to a slight increase in serum adiponectin, but significant
      decreases in gastrocnemius muscle and white adipose adiponectin (all p < 0.05).
      HFD for 4 weeks also resulted in a significant decrease in muscle adiponectin,
      which correlated with serum insulin, TG, and FFA (all p < 0.05). Treatment of the
      4-week HFD rats with a PPARgamma agonist GI262570 ameliorated the diet-induced
      hyperinsulinemia and dyslipidemia, and effectively restored muscle adiponectin
      (all p < 0.05). This study demonstrated that HFD-induced hyperinsulinemia and
      dyslipidemia appeared without changes in serum adiponectin, but were associated
      with decreased tissue adiponectin. This provides the first evidence for a
      connection between tissue adiponectin and diet-induced hyperinsulinemia and
      dyslipidemia.

PMID- 16414019
TI  - Prion protein-related proteins from zebrafish are complex glycosylated and
      contain a glycosylphosphatidylinositol anchor.
AB  - A hallmark of prion diseases in mammals is a conformational transition of the
      cellular prion protein (PrP(C)) into a pathogenic isoform termed PrP(Sc). PrP(C)
      is highly conserved in mammals, moreover, genes of PrP-related proteins have been
      recently identified in fish. While there is only little sequence homology to
      mammalian PrP, PrP-related fish proteins were predicted to be modified with N
      linked glycans and a C-terminal glycosylphosphatidylinositol (GPI) anchor. We
      biochemically characterized two PrP-related proteins from zebrafish in cultured
      cells and show that both zePrP1 and zeSho2 are imported into the endoplasmic
      reticulum and are post-translationally modified with complex glycans and a C
      terminal GPI anchor.

PMID- 16414020
TI  - Cloning and characterization of the 5'-flanking region of the Ehox gene.
AB  - The paired-like homeobox-containing gene Ehox plays a role in embryonic stem cell
      differentiation and is highly expressed in the developing placenta and thymus. To
      understand the mechanisms of regulation of Ehox gene expression, the 5'-flanking
      region of the Ehox gene was isolated from a mouse BAC library. 5'-RACE analysis
      revealed a single transcriptional start site 130 nucleotides upstream of the
      translation initiation codon. Transient transfection with a luciferase reporter
      gene under the control of serially deleted 5'-flanking sequences revealed that
      the nt -84 to -68 region contained a positive cis-acting element for efficient
      expression of the Ehox gene. Mutational analysis of this region and
      oligonucleotide competition in the electrophoretic mobility shift assay revealed
      the presence of a CCAAT box, which is a target for transcription nuclear factor Y
      (NFY). NFY is essential for positive gene regulation. No tissue-specific enhancer
      was identified in the 1.9-kb 5'-flanking region of the Ehox gene. Ehox is
      expressed during the early stages of embryo development, specifically in the
      brain at 9.5 dpc, as well as during the late stages of embryo development. These
      results suggest that NFY is an essential regulatory factor for Ehox
      transcriptional activity, which is important for the post-implantation stage of
      the developing embryo.

PMID- 16414021
TI  - Haemochromatosis gene (HFE) mutations in viral-associated neoplasia: Linkage to
      cervical cancer.
AB  - The present study examines the frequency of the two main HFE mutations (C282Y and
      H63D) in a randomly selected population of 346 individuals including 201 DNA
      samples from women with cervical neoplasia (including high-grade squamous
      intraepithelial lesions and invasive squamous cell carcinoma) and a control
      population of 146 women from the same geographical area. We found a significantly
      lower risk of development of cervical neoplasia in H63D carriers (OR = 0.56; 95%
      CI 0.35-0.92; p = 0.01). Multivariate logistic regression analysis confirms this
      observation (OR = 0.55; 95% CI 0.35-0.88, p = 0.01). Regarding the C282Y mutation
      no association was found (OR = 1.32; 95% CI 0.53-3.33; p = 0.52). In addition, a
      significant difference between H63D carrier and non-carrier women on the time-to
      onset of cervical lesions was observed (log-rank test: p = 0.0012). These results
      indicate that HFE could be considered a candidate modifier gene of viral-related
      neoplasia such as cervical carcinoma possibly by a dual role on iron metabolism
      and immunological system.

PMID- 16414022
TI  - Effects of human soluble epoxide hydrolase polymorphisms on isoprenoid phosphate
      hydrolysis.
AB  - Soluble epoxide hydrolase (sEH) is highly expressed in human liver and contains a
      C-terminal epoxide hydrolase activity and an N-terminal phosphatase activity.
      Endogenous C-terminal hydrolase substrates include arachidonic acid epoxides,
      however, data are limited regarding possible endogenous substrates for the N
      terminal phosphatase. Possible sEH N-terminal substrates include isoprenoid
      phosphate precursors of cholesterol biosynthesis and protein isoprenylation.
      Here, we report the kinetic analysis for a range of sEH isoprenoid substrates. We
      also provide an analysis of the effects of human sEH polymorphisms on isoprenoid
      hydrolysis. Interestingly, the Arg287Gln polymorphism recently suggested to be
      involved in hypercholesterolemia was found to possess a higher isoprenoid
      phosphatase activity than the wild type sEH. Consistent with the finding of
      isoprenoid phosphates as substrates for sEH, we identified isoprenoid-derived N
      terminal inhibitors with IC50 values ranging from 0.84 (+/-0.9) to 55.1 (+/-30.7)
      microM. Finally, we evaluated the effects of the different isoprenoid compounds
      on the C-terminal hydrolase activity.

PMID- 16414023
TI  - An unexpected inhibitory activity of Kunitz-type serine proteinase inhibitor
      derived from Boophilus microplus trypsin inhibitor on cathepsin L.
AB  - Several BPTI-Kunitz-type serine proteinase inhibitors were described in tick
      Boophilus microplus and Rhipicephalus sanguineus species. In this work, we
      present a synthetic gene based on two tick BPTI-Kunitz-type serine proteinase
      inhibitors, the first domain of B. microplus trypsin inhibitor-A (BmTI-A) and the
      carrapatin, the inhibitors were named BmTIsint and BmTIsint Mut. Our present
      results showed that BmTIsint and BmTIsint Mut inhibited trypsin (K(i) 3.3 and 1.0
      nM) and human plasma kallikrein (K(i) 16.5 and 35 nM), but in contrast to BmTI-A,
      the inhibitors did not inhibit human neutrophil elastase. BmTIsint was able to
      produce immunological response in mice but not in bovines. In addition, it is the
      first description of a BPTI-Kunitz-type inhibitor as a cysteine proteinase
      inhibitor, BmTIsint apparent dissociation constant (K(i)) for cathepsin L was 108
      nM. Our findings open the possibility up to obtain new molecules as potent serine
      or cysteine proteinase inhibitors using BmTIsint as a model.

PMID- 16414024
TI  - Effects of microcystins on human polymorphonuclear leukocytes.
AB  - Microcystins (MCs) are cyclic heptapeptides produced by cyanobacteria present in
      water contaminated reservoirs. Reported toxic effects for microcystins are liver
      injury and tumour promotion. In this study, we evaluated the effects of two MCs,
      MC-LR and [Asp(3)]-MC-LR, on human neutrophil (PMN). We observed that even at
      concentrations lower than that recommended by World Health Organization for
      chronic exposure (0.1 nM), MCs affect human PMN. Both MCs have chemotactic
      activity, induce the production of reactive oxygen species, and increase
      phagocytosis of Candida albicans. MC-LR also increased C. albicans killing. The
      effect of MCs on PMN provides support for a damage process mediated by PMN and
      oxidative stress, and may explain liver injury and tumour promotion associated to
      long-term MCs exposures.

PMID- 16414025
TI  - Role of the second transmembrane domain of rat adenosine A1 receptor in ligand
      receptor interaction.
AB  - Initial mutagenesis studies exploring the ligand recognition model of A1
      adenosine receptor (A1R) mainly focused on the residues in the 5th-7th
      transmembrane domains (TMs5-7). Little is known about the role of residues in
      TM2. To explore the importance of reserved hydrophobic region in TM2 of A1R, we
      mutated the hydrophobic residues at positions 65 and 69 to hydrophilic residues
      (L65T, Leu-65 to Thr-65; I69T, Ile-69 to Thr-69; I69S, Ile-69 to Ser-69) to
      change the hydrophobicity at the outer end of TM2. Binding assays showed that the
      affinities of mutant receptors were significantly decreased for ribose group
      containing agonists (2-chloro-N6-cyclopentyladenosine (CCPA) and 5'-N-ethyl
      carboxamidoadenosine (NECA)) but not for antagonists, N6-cyclopentyl-9
      methyladenine (N-0840), an adenine derivative lacking ribose group, and 8
      cyclopentyl-1, 3-dipropylxanthine (DPCPX), a xanthine derivative. This
      observation suggests that the hydrophobic region at the outer end of TM2 may
      mediate the recognition of the ribose group of CCPA and NECA.

PMID- 16414026
TI  - Methionine dependence of tumours: a biochemical strategy for optimizing
      paclitaxel chemosensitivity in vitro.
AB  - Methionine dependence is a unique feature of cancer cells characterized by growth
      and cell cycle arrest (typically in S and G2/M) under conditions of methionine
      depletion. Following replenishment of media with methionine, the cell cycle
      blockade is reversible and during this recovery period, cells may become more
      susceptible to the action of cell cycle specific drugs. The response of a panel
      of methionine dependent (HTC, Phi-1, PC3 and 3T3) cells to vinblastine and
      paclitaxel was compared to methionine independent Hs-27 cells under conditions of
      methionine depletion (M-H+; methionine depleted media supplemented with
      homocysteine) and starvation (M-H-; media without methionine or homocysteine).
      All cell lines were significantly more resistant to both agents under M-H+ and M
      H- conditions compared to controls under normal culture conditions [M+H-];
      however, the magnitude of resistance was reduced in the methionine independent Hs
      27 cells. During recovery from methionine depletion and starvation, the response
      of the methionine dependent cells to vinblastine and paclitaxel was significantly
      enhanced compared to controls. Although the activity of vinblastine on the Hs-27
      cell line was comparable to controls, these methionine independent cells became
      significantly more resistant to paclitaxel during recovery studies (IC50 = 2.13
      +/- 0.5 microM) compared to control cultures (IC50 = 0.13 +/- 0.15 microM).
      Whilst the mechanism responsible for this remains uncertain, the increased
      activity of paclitaxel against methionine dependent cells in conjunction with the
      decreased activity against Hs-27 cells suggests that methionine depletion
      strategies may enhance the therapeutic index of paclitaxel.

PMID- 16414027
TI  - Inhibitory effect of dietary phenolic compounds on Chlamydia pneumoniae in cell
      cultures.
AB  - Chlamydial infections are very common worldwide. All chlamydial species have a
      tendency to cause persistent infections, which have been associated to several
      chronic diseases including blinding trachoma, infertility and coronary heart
      disease (CHD). At present, no efficient treatment for the eradication of chronic
      chlamydial infections exists and, thus, new antichlamydial compounds are urgently
      needed. This study was designed to screen antichlamydial activity of natural
      flavonoids and other natural and structurally similar synthetic compounds against
      Chlamydia pneumoniae in human cell line (HL). HL cells were infected with C.
      pneumoniae and incubated 72 h with studied compounds. Reduction in the number of
      inclusions was determined with immunofluorescence staining. In vitro minimum
      inhibitory concentration was also determined for some of the most active
      compounds. Thirty seven percentage of the studied compounds (57 in total) were
      highly active against C. pneumoniae and all the studied compounds were non-toxic
      to the host cells at studied concentrations. Our study revealed direct
      antichlamydial effect for selected polyphenolic compounds against C. pneumoniae,
      in vitro. We also demonstrated the ability of some of the investigated compounds
      to accumulate inside cells or into cell membranes and cause inhibition, even when
      present only prior to infection.

PMID- 16414029
TI  - Smaller cingulate volumes in unipolar depressed patients.
AB  - BACKGROUND: The anterior cingulate cortex is a key structure in brain networks
      involved in mood regulation. Abnormalities in this brain region are possibly
      implicated in the pathophysiology of depression. This anatomical magnetic
      resonance imaging (MRI) study compared cingulate cortex volumes in unipolar
      depressed patients and age- and gender-matched healthy control subjects. METHODS:
      Thirty-one unmedicated DSM-IV unipolar patients (24 female, aged 39.2 +/- 11.9
      years [mean +/- SD]) and 31 healthy control subjects (24 female, aged 36.7 +/-
      10.7 years) were studied in a 1.5-T GE Signa magnet (General Electric Medical
      Systems, Milwaukee, Wisconsin). Cingulate volumes were compared by analysis of
      covariance with intracranial volume as the covariate. RESULTS: The unipolar
      patients had significantly smaller anterior and posterior cingulate volumes
      bilaterally compared with healthy control subjects. When patients were divided
      into currently depressed (n = 21) and remitted (n = 10) subgroups, currently
      depressed patients had significantly smaller anterior and posterior cingulate
      volumes bilaterally compared with healthy control subjects, whereas remitted
      patients had significantly smaller left anterior cingulate volumes compared with
      healthy individuals. CONCLUSIONS: Gray matter abnormalities in the cingulate
      cortex are implicated in the pathophysiology of unipolar depression. Smaller
      cingulate volumes in currently depressed patients support the hypothesis that
      cingulate cortex abnormalities are state dependent, whereas changes in left
      anterior cingulate might be trait related.

PMID- 16414028
TI  - Distribution of serotonin transporter labeled fibers in amygdaloid subregions:
      implications for mood disorders.
AB  - BACKGROUND: The serotonin transporter 5-HTT mediates responses to serotonin
      reuptake inhibitors (SSRIs), a mainstay treatment in mood disorders. The
      amygdala, a key emotional processing center, has functional abnormalities in mood
      disorders, which resolve following successful SSRI treatment. To better
      understand the effects of SSRIs in mood disorders, we examined the distribution
      of 5-HTT labeled fibers relative to specific nuclear groups in the amygdala.
      METHODS: Immunocytochemical techniques were used to chart 5-HTT labeled fibers in
      the amygdala in coronal sections through the brain of six adult Macaques. Nissl
      staining was used to define nuclear groups in the amygdala. RESULTS: The
      serotonin transporter 5-HTT is distributed heterogeneously in the primate
      amygdala, with the lateral subdivision of the central nucleus, intercalated cell
      islands, amygdalohippocampal area, and the paralaminar nucleus showing the
      heaviest concentrations. CONCLUSIONS: 5HTT-labeled fibers are very densely
      concentrated in output regions of the amygdala. High concentrations of 5-HTT
      positive fibers in the central nucleus indicate that tight regulation of
      serotonin is critical in modulating fear responses mediated by this nucleus. High
      concentrations of 5-HTT-labeled fibers in the intercalated islands and
      parvicellular basal nucleus/paralaminar nucleus, which contain immature 
      appearing neurons, suggest a potential trophic role for serotonin in these
      subregions.

PMID- 16414030
TI  - Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in
      bipolar disorder: a cross-sectional study.
AB  - BACKGROUND: Neuroimaging data suggest that deficits in ventral prefrontal cortex
      (VPFC) function in bipolar disorder (BD) progress during adolescence and young
      adulthood. However, the developmental trajectory of VPFC morphological
      abnormalities in BD is unknown. This study investigated potential age-dependent
      volume abnormalities in VPFC in BD. METHODS: Thirty-seven individuals diagnosed
      with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy
      comparison subjects (HC) participated in imaging. Gray and white matter volumes
      of VPFC were measured using high-resolution structural magnetic resonance imaging
      (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes
      across age groups while co-varying for total brain volume. Potential effects of
      illness features including rapid-cycling and medication were explored. RESULTS:
      VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction
      was significant (p = .01). Relative to HC subjects, VPFC gray and white matter
      volumes were significantly smaller in BD patients only in young adulthood (p =
      .04). In participants with BD, VPFC volumes were significantly smaller in
      participants with rapid-cycling than participants without rapid-cycling (p =
      .02). Conversely, current use of medication was associated with larger VPFC gray
      matter volumes (p = .005), independent of age. CONCLUSIONS: These preliminary
      findings suggest the presence of a more rapid initial decline in VPFC volumes
      with age in adolescents and young adults with BD than HC. These findings also
      suggest that the rapid-cycling subtype of BD is associated with larger VPFC
      volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may
      have trophic or protective effects on VPFC volumes in BD patients.

PMID- 16414031
TI  - Cognitive function in late life depression: relationships to depression severity,
      cerebrovascular risk factors and processing speed.
AB  - BACKGROUND: A number of studies have examined clinical factors linked to worse
      neuropsychological performance in late life depression (LLD). To understand the
      influence of LLD on cognition, it is important to determine if deficits in a
      number of cognitive domains are relatively independent, or mediated by depression
      related deficits in a basic domain such as processing speed. METHODS: Patients
      who met DSM-IV criteria for major depression (n = 155) were administered a
      comprehensive neuropsychological battery of tasks grouped into episodic memory,
      language, working memory, executive function, and processing speed domains.
      Multiple regression analyses were conducted to determine contributions of
      predictor variables to cognitive domains. RESULTS: Age, depression severity,
      education, race and vascular risk factors all made significant and independent
      contributions to one or more domains of cognitive function, with all five making
      independent contributions to processing speed. Age of onset made no independent
      contribution, after accounting for age and vascular risk factors. Of the five
      cognitive domains investigated, changes in processing speed were found to most
      fully mediate the influence of predictor variables on all other cognitive
      domains. CONCLUSIONS: While slowed processing speed appears to be the most core
      cognitive deficit in LLD, it was closely followed by executive function as a core
      cognitive deficit. Future research is needed to help clarify mechanisms leading
      to LLD- related changes in processing speed, including the potential role of
      white matter abnormalities.

PMID- 16414032
TI  - Localization of the scaffolding protein RACK1 in the developing and adult mouse
      brain.
AB  - RACK1 is a multifunctional scaffolding protein known to be involved in the
      regulation of various signaling cascades in the central nervous system (CNS). In
      order to gain insight into the neurological functions of RACK1, we examined the
      expression of RACK1 mRNA and protein during gestation and in the adult mouse
      brain. Several expression patterns were observed. At embryonic day 11.5 (E11.5),
      RACK1 is expressed in a high-dorsal to low-ventral gradient throughout the brain.
      At E13.5, RACK1 is most abundant in the telencephalon. In the developing cortical
      primordium, RACK1 protein is expressed in a high-rostromidline to low
      caudolateral gradient that appears to be regulated post-transcriptionally. At
      E18.5, RACK1 is expressed most abundantly in layers 1-4 of the cortex, striatum,
      hippocampus, dentate gyrus and specific thalamic nuclei. In the adult mouse,
      RACK1 is ubiquitously expressed in neuronal perikarya in most brain regions, with
      relatively higher levels in hippocampus, olfactory bulb, cortex and cerebellum.
      Subcellular staining was detected mainly in the cell bodies and extending into
      dendrites, whereas RACK1 was not present significantly in axonal fibers or
      nuclei. We also determined brain regions in which RACK1 interacts with one of its
      binding partners, the betaII isoform of protein kinase C (betaIIPKC). We found
      that betaIIPKC had a much more restricted expression pattern than RACK1 and
      overlapped with the scaffolding protein only in certain regions, including the
      CA1 area of the hippocampus, cerebellum and striatum. Our results suggest an
      important role for RACK1 during CNS development and support multiple functions of
      the protein in the adult brain.

PMID- 16414033
TI  - DFT study of alpha- and beta-D-galactopyranose at the B3LYP/6-311++G** level of
      theory.
AB  - Forty-one conformations of alpha- and beta-d-galactopyranose were geometry
      optimized using the B3LYP density functional and 6-311++G** basis set. Full
      geometry optimization was performed on different ring geometries and different
      hydroxymethyl rotamers (gg/gt/tg). Analytically derived Hessians were used to
      calculate zero point energy, enthalpy, and entropy. The lowest energy and free
      energy conformation found is the alpha-gg-(4)C(1)-c chair conformation, which is
      of lower electronic and free energy than the lowest energy alpha-d-glucopyranose
      conformer because of favorable hydrogen-bonding interactions. The in vacuo
      calculations showed considerable ( approximately 2.2kcal/mol) energetic
      preference for the alpha over the beta anomer for galactopyranose in both the
      (4)C(1) and (1)C(4) chair conformations. Results are compared to glucopyranose
      and mannopyranose calculations in vacuo. Boat and skew-boat forms were found that
      remained stable upon gradient optimization, although many starting conformations
      moved to other boat forms upon optimization. As with glucopyranose and
      mannopyranose, the orientation and interaction of the hydroxyl groups make the
      most significant contributions to the conformation-energy relationship in vacuo.

PMID- 16414034
TI  - Selective chemical depolymerization of rhamnogalacturonans.
AB  - A method was developed to selectively methyl esterify and then cleave GalA
      residues in pectic polysaccharides. The method was optimized using a
      rhamnogalacturonan (RG) from Arabidopsis mucilage as a model compound. The
      carboxyl group of the GalA residues in the RG was selectively methyl esterified
      using tetrabutylammonium fluoride and iodomethane in Me(2)SO containing 8% water.
      A 1D HMQC NMR method to determine the degree of methyl esterification was
      developed using (13)C-iodomethane as the methylating agent. The methyl-esterified
      pectins were fragmented by beta-elimination in 0.2M sodium borate, pH7.3, at 125
      degrees C. The resulting oligoglycosyl fragments, which contain a nonreducing 4
      deoxy-beta-l-threo-hex-4-enepyranosyluronic acid residue, were characterized
      using MALDI-TOF mass spectrometry, monosaccharide composition analysis, and 1D
      and 2D (1)H and (13)C NMR spectroscopy. Application of this method to branched RG
      from potato generated low-molecular-weight fragments containing two residues from
      the RG backbone and a single side chain. In contrast, the fragments obtained when
      RG is treated with RG lyase contain a minimum of four backbone residues. The
      chemical method thus facilitates the release and structural characterization of
      the side-chain structures of RG obtained from various plant sources. The method
      also provides a convenient method for generating fully or partially methyl
      esterified homogalacturonans.

PMID- 16414035
TI  - Facile synthesis toward the construction of an activity probe library for
      glycosidases.
AB  - Chemical probes that selectively label the glycoside hydrolase (GH) subfamilies
      have proven to be a powerful tool in GH-related research. We have previously
      demonstrated the design and synthesis of an activity probe for beta-glucosidase
      adopting a cassette-like design in a model study. Herein we report an improved
      synthetic route using (4-hydroxyphenyl)acetic acid 2-cyanoethyl ester as the
      precursor for the latent trapping device. Parallel syntheses were performed for
      the preparation of a library based on the structure of a key intermediate. The
      recognition head of this library covers a series of six sugars, including alpha-
      and beta-d-Glc, alpha- and beta-d-Gal, alpha-d-Man, and alpha-l-Fuc. Each member
      in this versatile intermediate library could serve as the building block in
      constructing an activity probe for GHs. As demonstrated in this study, three
      probes that have the 1,2-cis configuration were thus prepared for the first time
      to target alpha-d-glucosidase, alpha-d-galactosidase, and alpha-l-fucosidase,
      respectively.

PMID- 16414037
TI  - EPR spin label study of walnut oil effects on phosphatidylcholine membranes.
AB  - Effects of walnut oil (WO) on dynamic and thermodynamic properties of 0-50 wt%
      cholesterol (CH) containing dimyristoylphosphatidylcholine (DMPC) and 10 wt% CH
      containing dipalmitoylphosphatidylcholine (DPPC) membrane dispersions were
      studied by electron paramagnetic resonance (EPR), using 5-doxyl stearic acid (5
      DSA) and 16-doxyl stearic acid (16-DSA). Incorporation of 10 wt% WO alone
      decreased the phase transition temperature and created depth-dependent effects at
      the gel phase. The order increased close to the head region and decreased in the
      hydrocarbon core of the DMPC bilayer. For DPPC, the order decreased both close to
      head region and in the hydrocarbon core. Ten weight percent WO did not have
      considerable effect at the fluid phase for both DMPC and DPPC. Incorporation of
      40 wt% WO into DMPC created an abrupt decrease in the maximum hyperfine splitting
      values after 305 K. The effect of 10 wt% WO in CH containing DMPC dispersions was
      dependent on the CH concentration. An increase and a decrease in the order were
      observed at low and high CH concentrations, respectively. Incorporation of WO
      created different effects on fluidity of 10 wt% CH containing DMPC and DPPC
      dispersions. Close to the head group region, the order in DMPC increased both in
      the gel and fluid phases; but for DPPC, an opposite effect was observed in both
      of the phases. In the hydrocarbon core of the bilayer, addition of 10 wt% WO into
      10 wt% CH containing DMPC decreased the order in the gel phase and WO did not
      affect the order in the fluid phase. For DPPC, WO effects were observed to alter
      with temperature. In the studied temperature range, order parameters, diffusion
      constants and effective tilt angles were obtained from simulations of the spectra
      using Microscopic Order Macroscopic Disorder (MOMD) and Vary Anisotropic
      Reorientation (VAR) models. For 16-DSA, spectra were also simulated using two
      domains with EPRSIM.

PMID- 16414036
TI  - The activation-induced expression of DHX32 in Jurkat T cells is specific and
      involves calcium and nuclear factor of activated T cells.
AB  - In this report, we studied DHX32 expression in human Jurkat T cells. Co
      stimulation of CD3 and CD28 resulted in upregulation of DHX32. No significant
      changes in the expression of the closely related RNA helicases were seen.
      Ionomycin treatment alone was sufficient to upregulate the expression of DHX32
      mRNA isoform transcribed from the proximal promoter. We cloned DHX32 proximal
      promoter and identified a 218bp fragment containing two potential binding sites
      for the transcription factor nuclear factor of activated T cells (NF-AT).
      Mutation of core sequence of NF-AT resulted in reduced transcriptional activity,
      with more reduction observed in the second NF-AT site. Electrophoretic mobility
      shift assay results were consistent with a specific binding of NF-AT from
      ionomycin stimulated nuclear extract of Jurkat cells to oligonucleotide probes
      from DHX32 proximal promoter. These results suggest that the DHX32 expression is
      modulated in Jurkat T cells via a pathway that involves NF-AT.

PMID- 16414038
TI  - Negative urine opioid screening caused by rifampin-mediated induction of
      oxycodone hepatic metabolism.
AB  - INTRODUCTION: Oxycodone has become widely used in the clinic for the treatment of
      chronic pain. This reflects its favorable pharmacokinetics and side effect
      profiles. CASE REPORT: We report a 60-y-old man who had a clinically significant
      drug interaction between rifampin and oxycodone, resulting in 3 consecutive
      negative urine oxycodone screens in a 2-month period, suggesting non-adherence. A
      combination of urine opioid metabolite quantification by GC/MS and CYP genotyping
      confirmed that he was compliant with his oxycodone therapy. Determination of the
      complete oxycodone metabolite profile and the CYP3A4/5 and 2D6 genotype allowed
      the physician to be confident that the patient was compliant with the medication
      (and not diverting it) and to increase his oxycodone dose to optimize his pain
      control. CONCLUSION: This case demonstrates how the combination of analytical
      toxicology and pharmacogenetic analyses enhances a physician's ability to
      personalize drug therapy in patients with chronic pain syndromes.

PMID- 16414039
TI  - Bile acylcarnitine profiles in pediatric liver disease do not interfere with the
      diagnosis of long-chain fatty acid oxidation defects.
AB  - BACKGROUND: Plasma acylcarnitine measurement is an important diagnostic tool for
      inherited disorders of fatty acid and organic acid metabolism. Biliary excretion
      has been shown to be the primary route of excretion for acylcarnitines and
      analysis of bile acylcarnitine profiles may provide greater sensitivity for
      detecting metabolic disorders. Disorders of fatty acid oxidation frequently
      present with deranged liver function and the effect of hepatic disease on biliary
      acylcarnitine excretion are unknown. METHODS: We measured biliary acylcarnitine
      levels in pediatric patients aged 6 months to 1 year undergoing open liver biopsy
      with prospectively determined non-metabolic liver disease in order to determine
      the effect of the liver disease on acylcarnitine excretion. Bile was collected in
      syringes and was transported immediately and stored at -70 degrees C until the
      time of testing. The disease patient population consisted of 2 patients with
      known defects in long- and short-chain fatty acid oxidation (long-chain L-3
      hydroxy acyl-CoA dehydrogenase: LCHAD and short-chain L-3-hydroxy acyl-CoA
      dehydrogenase: SCHAD). The sample from the LCHAD patient was collected at autopsy
      and the patient with SCHAD deficiency was subsequently diagnosed as part of the
      prospective study and removed from the unknown etiology group. Acylcarnitine
      profiles were obtained for each specimen as butylated derivatives using tandem
      mass spectrometry. RESULTS: The non-metabolic liver disease had no effect on the
      diagnostic value of bile acylcarnitine levels for detecting LCHAD deficiency. The
      concentrations of bile long-chain acylcarnitine species analyzed from patients
      with non-metabolic liver disease were far lower than the levels seen in LCHAD
      deficiency which also demonstrated a characteristic pattern of 3
      hydroxyacylcarnitine excretion. In SCHAD deficiency, for which pathognomonic
      markers have not yet been established, bile analysis did not improve the
      diagnostic ability. CONCLUSION: The analysis of bile acylcarnitines for the
      diagnosis of long-chain fatty acid oxidation defects will provide unbiased
      information even in the presence of severe non-metabolic liver disease.

PMID- 16414041
TI  - Evidence that autocrine signaling through Bmpr1a regulates the proliferation,
      survival and morphogenetic behavior of distal lung epithelial cells.
AB  - Lung development requires reciprocal epithelial/mesenchymal interactions,
      mediated by signaling factors such as Bmps made in both cell populations. To
      address the role of Bmp signaling in the epithelium, we have exploited the fact
      that Bmp receptor type Ia (Alk3) is expressed in the epithelium during branching
      morphogenesis. Deletion of Bmpr1a in the epithelium with an Sftpc-cre transgene
      leads to dramatic defects in lung development. There is reduced epithelial
      proliferation, extensive apoptosis, changes in cell morphology and extrusion of
      cells into the lumen. By E18.5, there are fewer Type II cells than normal, and
      the lung contains large fluid-filled spaces. If cell death is prevented by making
      embryos homozygous null for the proapoptotic gene, Bax, the epithelial cells that
      are rescued can apparently differentiate, but normal morphogenesis is not
      restored. To determine whether Bmps made by the epithelium can function in an
      autocrine manner, mesenchyme-free endoderm was cultured in Matrigel with Fgfs.
      Under these conditions, the mutant epithelium fails to undergo secondary budding.
      Abnormal development was also seen when Bmp4 was specifically deleted in the
      epithelium using the Sftpc-cre transgene. Our results support a model in which
      Bmp signaling primarily regulates the proliferation, survival and morphogenetic
      behavior of distal lung epithelial cells.

PMID- 16414040
TI  - Modulation of AP and DV signaling pathways by the homeotic gene Ultrabithorax
      during haltere development in Drosophila.
AB  - Suppression of wing fate and specification of haltere fate in Drosophila by the
      homeotic gene Ultrabithorax is a classical example of Hox regulation of serial
      homology (Lewis, E.B. 1978. Nature 276, 565-570) and has served as a paradigm for
      understanding homeotic gene function. We have used DNA microarray analyses to
      identify potential targets of Ultrabithorax function during haltere
      specification. Expression patterns of 18 validated target genes and functional
      analyses of a subset of these genes suggest that down-regulation of both anterior
      posterior and dorso-ventral signaling is critical for haltere fate specification.
      This is further confirmed by the observation that combined over-expression of
      Decapentaplegic and Vestigial is sufficient to override the effect of Ubx and
      cause dramatic haltere-to-wing transformations. Our results also demonstrate that
      analysis of the differential development of wing and haltere is a good assay
      system to identify novel regulators of key signaling pathways.

PMID- 16414042
TI  - Neurophysiologic and neuroimaging studies of brain plasticity in children with
      spastic cerebral palsy.
AB  - Patients with cerebral palsy (CP) may have some problems other than this motor
      impairment: mental retardation, epilepsy and sensory disturbance. Healthy
      children and children with CP have an enhanced capacity for learning and memory
      compared to adults. There are few tools for brain plasticity investigations. The
      utility of the neurophysiologic and MRI techniques in the determination of brain
      reorganization and repair in patients with cerebral palsy is described. The
      authors discuss their results of quantitative EEG and spectroscopy MRI studies in
      children with CP. Quantitative EEG and spectroscopy MRI can be useful tools in
      the determination of these processes in children with CP.

PMID- 16414043
TI  - Presence of a unique male-specific extension of C-terminus to the cytochrome c
      oxidase subunit II protein coded by the male-transmitted mitochondrial genome of
      Venustaconcha ellipsiformis (Bivalvia: Unionoidea).
AB  - Analyses of unionoidean bivalve male-transmitted (M) mtDNA genomes revealed an
      approximately 555 bp 3' coding extension to cox2. An antibody was generated
      against this predicted C-terminus extension to determine if the unique cox2
      protein is expressed. Western blot and immunohistochemistry analyses demonstrated
      that the protein was predominantly expressed in testes. Weak expression was
      detected in other male tissues but the protein was not detected in female
      tissues. This is the first report documenting the expression of a cox2 protein
      with a long C-terminus in animals. Its universal presence in unionoidean bivalve
      testes suggests a functional significance for the protein.

PMID- 16414044
TI  - BIOREL: the benchmark resource to estimate the relevance of the gene networks.
AB  - The progress of high-throughput methodologies in functional genomics has lead to
      the development of statistical procedures to infer gene networks from various
      types of high-throughput data. However, due to the lack of common standards, the
      biological significance of the results of the different studies is hard to
      compare. To overcome this problem we propose a benchmark procedure and have
      developed a web resource (BIOREL), which is useful for estimating the biological
      relevance of any genetic network by integrating different sources of biological
      information. The associations of each gene from the network are classified as
      biologically relevant or not. The proportion of genes in the network classified
      as "relevant" is used as the overall network relevance score. Employing synthetic
      data we demonstrated that such a score ranks the networks fairly in respect to
      the relevance level. Using BIOREL as the benchmark resource we compared the
      quality of experimental and theoretically predicted protein interaction data.

PMID- 16414045
TI  - Cholesterol loading augments oxidative stress in macrophages.
AB  - To investigate the molecular consequence of loading free cholesterol into
      macrophages, we conducted a large-scale gene expression study to analyze
      acetylated-LDL-laden foam cells (AFC) and oxidized-LDL-laden foam cells (OFC)
      induced from human THP-1 cell lines. Cluster analysis was performed using 9600
      gene microarray datasets from time course experiment. AFC and OFC shared common
      expression profiles; however, there were sufficient differences between these two
      treatments that AFC and OFC appealed as two separate entities. We identified 80
      commonly upregulated genes and 48 commonly downregulated genes in AFC and OFC.
      Functional annotation of the differentially expressed genes indicated that
      apoptosis, extracellular matrix, oxidative stress, and cell proliferation was
      deregulated. We also identified 87 differentially expressed genes unique for AFC
      and 31 genes for OFC. The uniquely expressed genes of AFC are associated with
      kinase activity, ATP binding activity, and transporter activity, while unique
      genes for OFC are associated with cell signaling and adhesion. To validate the
      hypothesis that oxidative stress is a common feature for AFC and OFC, we
      performed a cluster analysis employing the genes related to oxidative stress, but
      we were unable to distinguish AFC from OFC in this manner. We performed real-time
      RT-PCR and ELISA on foam cells to examine the transcripts and secreted protein of
      interleukin 1 beta (IL1beta). IL1beta was rapidly induced in foam cells, but for
      AFC both RNA level and protein level dropped immediately and was attenuated. To
      detect levels of reactive oxygen species in foam cells we conducted hydroethidine
      staining and observed high levels of superoxide anion. We conclude that loading
      free cholesterol induces high levels of superoxide anion, increases oxidative
      stress, and triggers a transient inflammatory response in macrophages.

PMID- 16414046
TI  - A mutant pyruvate dehydrogenase E1 subunit allows survival of Escherichia coli
      strains defective in 1-deoxy-D-xylulose 5-phosphate synthase.
AB  - The 2-C-methyl-D-erythritol 4-phosphate pathway has been proposed as a promising
      target to develop new antimicrobial agents. However, spontaneous mutations in
      Escherichia coli were observed to rescue the otherwise lethal loss of the first
      two enzymes of the pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase (DXS)
      and DXP reductoisomerase (DXR), with a relatively high frequency. A mutation in
      the gene encoding the E1 subunit of the pyruvate dehydrogenase complex was shown
      to be sufficient to rescue the lack of DXS but not DXR in vivo, suggesting that
      the mutant enzyme likely allows the synthesis of DXP or an alternative substrate
      for DXR.

PMID- 16414047
TI  - Hip fracture documentation-the impact of shift systems.
AB  - The recent reduction in junior doctors' hours has lead to a change in working
      patterns. The aim of this study was to assess the effect of this change on
      documentation in orthopaedic surgery. Over a 6-week period, 25 patients were
      admitted to our unit with hip fractures. During this period, all junior doctors
      worked on a 'full-shift' working pattern. For comparison a control group was
      formed comprising of 29 patients admitted with hip fractures over an earlier 6
      weeks when all junior doctors worked on a traditional 'on-call' system. The
      medical records of each patient were assessed for the quality of medical
      documentation using a published scoring system. The on-call group scored higher
      for the standard of documentation compared with the shift system group (mean 24.8
      versus mean 21.3), p<0.05. The on-call group also had fewer weekdays without any
      documented entries in the medical records compared to the shift system group
      (mean 3.2 days versus mean 4.0 days), p<0.05. A change in the working pattern for
      junior doctors has lead to a reduction in the quality of medical documentation.
      With more personnel working fewer hours, maintaining a high standard of
      documentation is essential for the good clinical care of patients.

PMID- 16414048
TI  - A new skatepark: the impact on the local hospital.
AB  - BACKGROUND: There has been a resurgence of skateboarding, rollerblading and BMX
      riding in recent years and in response dedicated skateparks have opened in many
      cities across the UK. It is acknowledged that these sports are associated with
      risk of injury and it is recommended that participants wear protective clothing.
      OBJECTIVE: We aimed to determine if the opening of a skatepark near our hospital
      had any effect on the number of skatepark related injuries attending the
      emergency department and to describe the types of injuries sustained. METHODS:
      All patients attending the emergency department with sports injuries were
      identified over 24 consecutive weeks. At the end of the 12th week a skatepark
      opened nearby. Data recorded prospectively included age and sex of subjects, the
      delay from injury to presenting to hospital, whether or not protective equipment
      was worn and if first aid was administered before attending hospital. The
      investigations performed in the emergency department, the diagnosis, treatment
      received and disposal from the hospital were also recorded. RESULTS: After the
      skatepark opened there was a significant increase in the number of skatepark
      related attendances from 7 to 32. Protective clothing was only worn by 9 out of
      39 of those with injuries. The commonest injuries were musculoskeletal and the
      limbs were injured more frequently than the head and trunk. CONCLUSION: We
      demonstrated a significant increase in the number of skatepark related injuries
      attending the emergency department following the opening of a nearby skatepark.

PMID- 16414049
TI  - Re-displacement of paediatric forearm fractures: role of plaster moulding and
      padding.
AB  - Re-displacement of paediatric forearm and wrist fractures following manipulation
      and cast application is a common complication. Poor plaster application technique
      is an important risk factor for re-displacement. However, there are no reliable
      and validated objective radiological measurements to differentiate a well-applied
      plaster cast from a poorly padded and moulded cast. This study was conducted in
      the background of this fact. We have attempted to define simple, reliable and
      objective radiological measurements to determine the quality of moulding and
      padding of the plaster thereby predicting re-displacement of fractures in this
      group. The two radiographic measurements used in this study are Cast index and
      Padding index, which are a guide to plaster moulding and padding, respectively.
      Case records and radiographs of 142 children who underwent a manipulation for a
      displaced fracture of forearm or wrist were studied. Angulation, translation
      displacement, Cast index and Padding index were measured on radiographs. The sum
      of the Cast index and Padding index was termed as the Canterbury index. Re
      displacement was seen in 44 cases (32.3%). Cast index, Padding index and
      Canterbury index were significantly greater in the re-displacement group as
      compared to the cases where no re-displacement was seen (p<0.005). Improvement in
      the plaster application skills as monitored by these indices reduced the re
      displacement rate by 50%. We suggest that a high Cast index of more than 0.8,
      Padding index of more than 0.3 and the combined Canterbury index of 1.1 are
      important risk factors for re-displacement of these fractures.

PMID- 16414051
TI  - Mid term results of PlantTan plate in the treatment of proximal humerus
      fractures.
AB  - This prospective study evaluates the clinical efficacy of a special implant,
      PlantTan plate used for fixation of displaced proximal humerus fractures. The
      PlantTan plate was used for internal fixation of closed displaced proximal
      humeral fractures in 68 patients from September 1999 to June 2002, in a
      University Hospital. One of the surgeries was for a non-union, and five patients
      were lost to follow-up. The patients' ages ranged from 19 to 76 years (mean 61
      years and median 66 years). Of the remaining 62 patients, 42 were female and 20
      were male. As defined using the Neer classification 19 patients had two part, 37
      three part and 6 had four part fractures. Median follow-up was 19 months (11-38).
      The outcome was assessed using radiographs, American Shoulder and Elbow Surgeons
      (ASES) score and Hospital for Special Surgery (HSS) scoring system. Fifty-two
      patients achieved union in a median of 8 weeks. The median cumulative score of
      activities of daily living of ASES was 20.4/30 (13-27). According to HSS, 11
      scored excellent, 26 good, 14 fair and 11 scored poor. Eight patients had
      fixation failure and two developed avascular necrosis. Eleven patients developed
      an infection. Six patients developed an infection resulting in implant removal.
      One had a transient and one permanent axillary nerve palsy. Since the PlantTan
      plate provides stability, early active rehabilitation can be instituted. The
      implant is distally placed reducing impingement symptoms. However, the implant
      requires wide surgical exposure, is bulky and has an unacceptable infection rate.
      The fixation failure is high in patients with osteoporosis. In view of the above
      encountered problems, the implant has been discontinued in our hospital.

PMID- 16414050
TI  - Characterisation of orthopaedic trauma admitted to adult level 1 trauma centres.
AB  - BACKGROUND: Despite the vast number of traumatic injuries that are orthopaedic in
      nature, comprehensive epidemiological data that characterise orthopaedic trauma
      are limited. The aim of this study was to investigate the nature of orthopaedic
      trauma admitted to adult Level 1 Trauma Centres. METHODS: Data were obtained from
      the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), which includes all
      patients with orthopaedic trauma admitted to the two adult Level 1 Trauma Centres
      in Victoria (Australia). Information was collected from the medical record and
      hospital databases on patients' demographics and injury event, diagnoses and
      management. RESULTS: Data were analysed on 784 patients recruited between August
      2003 and March 2004. Patients were mainly young (<65 years) (70.7%), male (59.1%)
      and injured in a transport collision (51.3%). Fractures of the femur (23.7%) and
      spine (23.5%) were the most common injuries and were predominately managed with
      operative (87.6%) and conservative (78.8%) methods, respectively. Differences in
      most parameters were evident between younger (<65 years) and older (> or =65
      years) patients. CONCLUSIONS: This study presents epidemiological data on
      patients with orthopaedic trauma who were admitted to adult Level 1 Trauma
      Centres. This information is critical for the future monitoring and evaluation of
      the outcomes of orthopaedic trauma.

PMID- 16414052
TI  - Asymmetric dimethylarginine is associated with macrovascular disease and total
      homocysteine in patients with type 2 diabetes.
AB  - BACKGROUND: The endogenous nitric oxide synthase inhibitor asymmetric
      dimethylarginine (ADMA) and total homocysteine (tHcy) are elevated in patients at
      increased cardiovascular risk. Patients with type 2 diabetes (T2DM) have higher
      incidence of macrovascular disease than the general population. Recent reports
      suggest a relationship between tHcy and ADMA. To evaluate the connection between
      ADMA and tHcy and macrovascular disease, we determined both risk factors in T2DM
      patients with and without macrovascular disease. SUBJECTS AND METHODS: Plasma
      concentrations of ADMA and tHcy were cross-sectionally determined in 136 T2DM
      patients. Fifty-five patients had macrovascular disease defined by history of
      stroke, myocardial infarction, coronary heart disease or peripheral arterial
      occlusive disease. Logistic regression analysis was performed to examine the
      relationship between macrovascular disease and these risk factors. Potential
      confounders were identified by significant Spearman rank correlation
      coefficients. RESULTS: In unadjusted models ADMA (per 0.1 micromol/l) and tHcy
      (per 5 micromol/l) were both significantly related to macrovascular disease
      (OR=1.63, 95% CI: 1.21-2.19 and OR=1.49, 95% CI: 1.04-2.14). In multivariate
      models, ADMA was significantly associated with macrovascular disease independent
      of l-arginine, albumin excretion rate, tHcy and glomerular filtration rate (GFR;
      OR=1.53, 95% CI: 1.04-2.26). The connection between tHcy and macrovascular
      disease was not independent of diastolic blood pressure, age, ADMA or GFR. Linear
      regression analyses revealed that ADMA, GFR and low-density lipoprotein
      cholesterol were independent predictors for tHcy. CONCLUSION: ADMA is associated
      with macrovascular disease independent of tHcy and traditional cardiovascular
      risk factors in patients with T2DM.

PMID- 16414053
TI  - Significance of small dense low-density lipoprotein-cholesterol concentrations in
      relation to the severity of coronary heart diseases.
AB  - We have investigated the clinical significance of small dense low-density
      lipoprotein-cholesterol (sd-LDL-C) concentrations in coronary heart disease
      (CHD). We measured the LDL size by gradient gel electrophoresis and quantified sd
      LDL-C concentrations by a newly developed rapid assay using heparin-magnesium
      precipitation in 225 consecutive CHD patients without any lipid-lowering
      medication and 142 healthy middle-aged subjects as controls. The LDL size was
      markedly smaller and sd-LDL-C levels were significantly higher in CHD patients
      than in controls of both sexes, whereas LDL-C levels were comparable between CHD
      and controls. The LDL-C levels were significantly higher in a subpopulation of 84
      patients with acute coronary syndrome than in other patients groups, while LDL
      size and high-density lipoprotein-cholesterol (HDL-C) were not found to vary
      among the patients. The sd-LDL-C increased as the number of diseased vessels or
      Gensini atherosclerosis score increased. Among the 123 stable CHD patients,
      multiple logistic regression analysis revealed that sd-LDL-C levels were
      significantly associated with the clinically severe cases requiring coronary
      revascularization independently of LDL-C, HDL-C and apolipoprotein B. The sd-LDL
      mass plays a more important role in the progression of CHD than the LDL size, and
      the sd-LDL-C concentration serves as a powerful surrogate marker for the
      prevention of CHD.

PMID- 16414054
TI  - Identification and refinement of a peptide affinity ligand with unique
      specificity for a monoclonal anti-tenascin-C antibody by screening of a phage
      display library.
AB  - Using phage display technology, a 22-mer peptide was selected as a ligand with
      unique specificity for the murine monoclonal ST2146 antibody that recognizes the
      EGF repeats region of the human tumor-associated antigen tenascin-C. This
      peptide, synthesized in an 8-branched form to enhance its binding properties, is
      useful in replacing the native antigen in the affinity and immunoreactivity
      characterization of the ST2146 antibody and its biotinylated derivatives.
      Affinity resins, prepared by immobilizing the mimotope or its shorter 10-mer
      binding unit on a chromatographic support, were able to capture ST2146 directly
      from the hybridoma supernatant, with antibody recovery and host cell protein
      (HCP) reduction similar to or better than protein A sorbent, a purity degree
      exceeding 95%, and full recovery of antibody activity. The affinity constants of
      both peptides, as determined by frontal analysis of broad-zone elution affinity
      chromatography and BiaCore measurements, were very similar and included in a
      range suitable for affinity ligands. Column capacity, determined by applying a
      large excess of purified ST2146 to 1 mL of column bed volume, was close to 50
      mg/mL for both resins. These matrices retain their ST2146 binding properties
      after various treatments, including sanitization, thus indicating very high
      stability in terms of ligand leakage and degradation. Moreover, the short form
      shows higher enzymatic stability, thus proving more suitable as ligand for ST2146
      affinity purification.

PMID- 16414055
TI  - Selective immunoclean-up followed by liquid chromatography for the monitoring of
      a biomarker of exposure to polycyclic aromatic hydrocarbons in urine at the ng l
      1 level.
AB  - A selective clean-up procedure using an immunosorbent (IS) was developed for the
      trace-level determination, in water and urine samples, of 3-benzo(a)pyrene
      glucuronide (3-BP-G), a biomarker of exposure to carcinogenic polycyclic aromatic
      hydrocarbons (PAHs). First, three sorbents used for the immobilization of
      antibodies were evaluated for their ability to limit the risk of non-specific
      interactions and to provide a high bonding density. The best sorbent, i.e.
      sepharose, was used for the immobilization of two different monoclonal
      antibodies. The most specific antibody for 3-BP-G was applied to the selective
      extraction from urine providing a clean extract, an easy and reliable
      quantification by comparison with a classical SPE process. The sensitivity of the
      fluorescence associated with the selectivity of the IS provides a limit of
      detection up to 1.2 ng l(-1) in urine for 3-BP-G.

PMID- 16414056
TI  - Comparative visualization for comprehensive two-dimensional gas chromatography.
AB  - This paper investigates methods for comparing datasets produced by comprehensive
      two-dimensional gas chromatography (GC x GC). Chemical comparisons are useful for
      process monitoring, sample classification or identification, correlative
      determinations, and other important tasks. GC x GC is a powerful new technology
      for chemical analysis, but methods for comparative visualization must address
      challenges posed by GC x GC data: inconsistency and complexity. The approach
      extends conventional techniques for image comparison by utilizing specific
      characteristics of GC x GC data and developing new methods for comparative
      visualization and analysis. The paper describes techniques that register (or
      align) GC x GC datasets to remove retention-time variations; normalize
      intensities to remove sample amount variations; compute differences in local
      regions to remove slight misregistrations and differences in peak shapes; employ
      color (hue), intensity, and saturation to simultaneously visualize differences
      and values; and use tools for masking, three-dimensional visualization, and
      tabular presentation with controls for graphical highlights to significantly
      improve comparative analysis of GC x GC datasets. Experimental results indicate
      that the comparative methods preserve chemical information and support
      qualitative and quantitative analyses.

PMID- 16414057
TI  - Hydrodynamic thickness of petroleum oil adsorbed layers in the pores of reservoir
      rocks.
AB  - The hydrodynamic thickness delta of adsorbed petroleum (crude) oil layers into
      the pores of sandstone rocks, through which the liquid flows, has been studied by
      Poiseuille's flow law and the evolution of (electrical) streaming current. The
      adsorption of petroleum oil is accompanied by a numerical reduction in the
      (negative) surface potential of the pore walls, eventually stabilizing at a small
      positive potential, attributed to the oil macromolecules themselves. After
      increasing to around 30% of the pore radius, the adsorbed layer thickness delta
      stopped growing either with time or with concentrations of asphaltene in the
      flowing liquid. The adsorption thickness is confirmed with the blockage value of
      the rock pores' area determined by the combination of streaming current and
      streaming potential measurements. This behavior is attributed to the effect on
      the disjoining pressure across the adsorbed layer, as described by Derjaguin and
      Churaev, of which the polymolecular adsorption films lose their stability long
      before their thickness has approached the radius of the rock pore.

PMID- 16414058
TI  - A simple approach to the synthesis of silver nanowires by hydrothermal process in
      the presence of gemini surfactant.
AB  - Silver nanowires were synthesized by the hydrothermal route in aqueous solution
      of gemini surfactant 1,3-bis(cetyldimethylammonium) propane dibromide (16-3-16)
      at a relatively low temperature. The as-prepared silver nanowires were
      characterized by X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction
      (XRD), transmission electron microscope (TEM), electron diffraction (ED), and UV
      vis absorption spectrum. The obtained silver nanowires are of high aspect ratios
      with an average diameter of approximately 30 nm and length ranging from several
      to tens of micrometers.

PMID- 16414059
TI  - Growth mechanism of ZnO nanocrystals with Zn-rich from dots to rods.
AB  - ZnO nanocrystals from dot to rod were synthesized by simply changing Zn2+
      concentration in ZnO seed solutions. The growth of ZnO nanocrystals was sensitive
      to the amount of Zn2+ in the solution. The growth process of ZnO from dot to rod
      was observed by optical spectra, transmission electron microscopy and X-ray
      diffraction spectra. From these results, the growth mechanism of ZnO from dots to
      rods was discussed.

PMID- 16414060
TI  - Coating of zinc ferrite particles with a conducting polymer, polyaniline.
AB  - Particles of zinc ferrite, ZnOFe2O3, were coated with polyaniline (PANI)
      phosphate during the in situ polymerization of aniline in an aqueous solution of
      phosphoric acid. The PANI-ferrite composites were characterized by FTIR
      spectroscopy. X-ray photoelectron spectroscopy was used to determine the degree
      of coating with a conducting polymer. Even a low content of PANI, 1.4 wt%,
      resulted in the 45% coating of the particles' surface. On the other hand, even at
      high PANI content, the coating of ferrite surface did not exceeded 90%. This is
      explained by the clustering of hydrophobic aniline oligomers at the hydrophilic
      ferrite surface and the consequent irregular PANI coating. The conductivity
      increased from 2 x 10(-9) to 6.5 S cm(-1) with increasing fraction of PANI
      phosphate in the composite. The percolation threshold was located at 3-4 vol% of
      the conducting component. In the absence of any acid, a conducting product, 1.4 x
      10(-2) Scm(-1), was also obtained. As the concentration of phosphoric acid
      increased to 3 M, the conductivity of the composites reached 1.8 S cm(-1) at 10
      14 wt% of PANI. The ferrite alone can act as an oxidant for aniline; a product
      having a conductivity 0.11 S cm(-1) was obtained after a one-month immersion of
      ferrite in an acidic solution of aniline.

PMID- 16414061
TI  - The characterisation of a novel, covalently modified, amphiphilic alginate
      derivative, which retains gelling and non-toxic properties.
AB  - The characterisation of a novel amphiphilic material, Alg-C4, produced from
      butanol linked by esterification to alginate is presented. The novel derivative
      retains the gelling and non-toxic properties of native alginate. FTIR spectra of
      Alg-C4 contained the characteristic hydroxyl and carboxyl bands, but also
      featured additional peaks at 1736 and 1134 cm(-1), indicating the presence of
      ester bonds. NMR studies showed the presence of butyl groups. The endothermic
      peak and exothermic peak present in the DSC thermogram of native alginate were
      also apparent in the Alg-C4 thermogram, but had shifted to lower temperatures
      (from 106 to 87 degrees C and from 254 to 247 degrees C, respectively). In
      addition, the exothermic peak was significantly reduced for Alg-C4 (5 mW compared
      to 20 mW in native alginate). Scanning electron microscopy was used to examine
      surface topography. The native alginate beads appeared smooth while Alg-C4 beads
      had a different, rougher appearance. Using circular dichroism it was found that
      the ratio of mannuronic to guluronic residues in the Alg-C4 was markedly
      increased compared to the native alginate (1.33 to 2.47), suggesting the
      preferential esterification of butanol to the guluronic residues. Exposure of
      ovarian granulosa cells in vitro to the Alg-C4 material demonstrated that
      granulosa cell viability (MTT test) was unchanged when compared to native
      alginate, which is regarded as non-toxic. The novel material is very stable,
      giving identical FTIR, DSC and gelling performance after 12 months storage at
      temperatures ranging from 10 to 20 degrees C. The data support the successful
      preparation of a stable modified alginate with characteristic hydrophilic
      properties and, in addition, a novel hydrophobic character.

PMID- 16414062
TI  - How metal (hydr)oxides are protonated in aqueous media: the (n+1) rule and the
      role of the interfacial potential.
AB  - The mechanism of the protonation of solid metal (hydr)oxides in aqueous media,
      which is closely interrelated to many processes of great technological and
      environmental importance, has been elucidated using simulation and experimental
      work. The electrical potential, smeared out at the interfacial region, changes
      the concentration of the H+ ions on the surface of the (hydr)oxide, thus
      promoting or hindering protonation. This is manifested by the shifts of the
      protonation peaks of the various kinds of surface sites and the appearance of an
      extra peak in the differential potentiometric titration curve.

PMID- 16414063
TI  - Effect of interfacial mobility on rupture of thin stagnant films on a solid
      surface due to random mechanical perturbations.
AB  - Previous analysis of Narsimhan [G. Narsimhan, J. Colloid Interface Sci. 287
      (2005) 624-633] for the evaluation of rupture of a nondraining thin film on a
      solid support due to imposed random mechanical perturbations modeled as a
      Gaussian white noise has been extended for partially mobile gas-liquid
      interfaces. The average rupture time of film is evaluated by first passage time
      analysis (as the mean time for the amplitude of perturbation to become equal to
      film thickness). The interfacial mobility is accounted for through surface
      viscosity as well as Marangoni effect. The mean rupture time for partially mobile
      gas-liquid interface, as characterized by two dimensionless groups, dimensionless
      surface viscosity and Marangoni number, lies between the two extreme limits for
      fully mobile and immobile films. The critical wavenumber for minimum rupture time
      is shown to be insensitive to interfacial mobility. However, the critical
      dimensionless surface viscosity and critical Marangoni number at which the
      behavior of thin film deviates from that of fully mobile film and the behavior
      approaches that of fully immobile film are smaller for higher Hamaker constants,
      smaller film thickness and smaller surface potentials.

PMID- 16414064
TI  - Thermodynamic characterization of the prevailing molecular interactions in mixed
      floating monolayers of phospholipids and usnic acid.
AB  - The investigation of the characteristics of mixed floating monolayers of
      phospholipids and usnic acid (UA), an active metabolite from lichens, can provide
      valuable information on how to prepare stable liposomes that could serve as
      carriers of UA for therapeutic proposes. The present paper is concerned with the
      thermodynamic analysis of the behavior of Langmuir monolayers formed by mixing
      different phospholipids (dibehenoylphosphatidylcholine, DBPC,
      dipalmitoylphosphatidylcholine, DPPC, and dioleoylphosphatidylcholine, DOPC) and
      UA at varied molar fractions. Relevant thermodynamic parameters such as excess
      areas, excess free energies and free energy of mixing were derived from the
      surface pressure data obtained from compression measurements performed in a
      Langmuir trough. For the largest lateral pressure examined (25 mN/m), negative
      values of the excess free energy were found only for the DOPC/UA monolayer, which
      should be the most stable of them. Based on the calculated values of the free
      energy of mixing, we note that the DBPC/UA and DPPC/UA systems present the best
      mixed character at low pressures and when the molar fraction of the UA is 0.5; at
      that relative concentration and at low values of the external pressure, the UA
      molecules can better mix and interact with the phospholipid molecules. The
      compression isotherms for mixed monolayers show no visible transitions,
      exhibiting a more organized phase that corresponds to a negative free energy of
      mixing. We have established that the most stable monolayers were those
      corresponding to DOPC/UA mixtures with a UA molar fraction of 0.75.

PMID- 16414065
TI  - Calculation of hydrophile-lipophile balance for polyethoxylated surfactants by
      group contribution method.
AB  - Based on Davies' group contribution method, hydrophile-lipophile balance (HLB)
      values were calculated by effective chain length (ECL) instead of actual chain
      length of straight alkyl chain, polyoxyethylene (EO) chain, and polyoxypropylene
      (PO) chain. Linear equations were adopted for the effective chain length of
      straight alkyl chain and PO chain; a Gamma probability density function (PDF) was
      used to describe the contribution of each EO group to HLB and the effective chain
      length of EO chain could be obtained by integrating Gamma PDF. The HLB values of
      224 nonionic surfactants were calculated and the average absolute error is less
      than 1.5, which is much better than the results obtained by Davies.

PMID- 16414066
TI  - In vitro and in vivo protein sampling by combined microdialysis and
      ultrafiltration.
AB  - Cytokines, chemokines and growth factors regulate inflammation, resistance to
      infection and tissue repair. Understanding their function within tissues is a
      priority in evolving therapy for a number of disease processes. Yet, the
      existence of complex networks of these factors in the tissue microenvironment has
      made understanding of their interactions difficult. We demonstrate the capability
      of microdialysis probes to recover small proteins efficiently in vitro. Further
      we show that microdialysis of human tissues allows for protein recovery from
      tissue interstitial fluid. This technology, combined with a multiplexed
      immunoassay, facilitates the simultaneous measurement of cytokines and chemokines
      in response to injury in the oral mucosa of human subjects in vivo.

PMID- 16414067
TI  - Integration specificity of phage phiC31 integrase in the human genome.
AB  - The site-specific integrase from bacteriophage phiC31 functions in mammalian
      cells and is being applied for genetic engineering, including gene therapy. The
      phiC31 integrase catalyzes precise, unidirectional recombination between its 30
      40-bp attP and attB recognition sites. In mammalian cells, the enzyme also
      mediates integration of plasmids bearing attB into native sequences that have
      partial sequence identity with attP, termed pseudo attP sites. Here, we analyzed
      the features of phiC31-mediated integration into pseudo attP sites in the human
      genome. Sequence analysis of 196 independent integration events derived from
      three cell lines revealed approximately 101 integration sites: 56% of the events
      were recurrent integrations distributed among 19 pseudo attP sequences.
      Bioinformatics analysis revealed a approximately 30-bp palindromic consensus
      sequence motif shared by all of the repeat occurrences and most of the single
      occurrence sites, verifying that phiC31-mediated integration into pseudo attP
      sites is significantly guided by DNA sequence recognition. The most favored
      unique sequence in these cell lines occurred at chromosome 19q13.31 and accounted
      for 7.5% of integration events. Other frequent integration sites were in three
      specific sequences in subfamilies of ERVL and L1 repetitive sequences, accounting
      for an additional 17.9% of integration events. Integrations could occur in either
      orientation at a pseudo attP site, were often accompanied by small deletions, and
      typically occurred in a single copy per cell. A number of aberrant events were
      also described, including large deletions and chromosome rearrangements. phiC31
      integrase-mediated integration only slightly favored genes and did not favor
      promoter regions. Gene density and expression studies suggested chromatin context
      effects. An analysis of the safety of integration sites in terms of proximity to
      cancer genes suggested minimal cancer risk. We conclude that integration systems
      derived from phiC31 integrase have great potential utility.

PMID- 16414068
TI  - An unusual structure at one end of potato potyvirus particles.
AB  - The particles of potato virus Y (PVY) and potato virus A (PVA) potyviruses are
      helically constructed filaments that are thought to contain a single type of coat
      protein subunit. Examination of negatively stained virions by electron microscopy
      reveals flexuous rod-shaped particles with no obvious terminal structures. It is
      known that some helically constructed rod-shaped virus particles incorporate
      additional minor protein components, which form stable complexes that mediate
      particle disassembly, movement or transmission by vectors. Some of this
      information has been obtained using imaging techniques such as atomic force
      microscopy. The particles of PVY and PVA were examined by atomic force microscopy
      and immunogold labelling electron microscopy. Our results show that some of the
      potyvirus particles contain a protruding tip at one end of the virus particles,
      which is presumably associated with the 5'-end of viral RNA. The tip contains the
      virus-encoded proteins genome-linked protein and helper-component proteinase. The
      composition and possible roles of the terminal tip structures in virus biology
      are discussed.

PMID- 16414069
TI  - X-ray structures of free and leupeptin-complexed human alphaI-tryptase mutants:
      indication for an alpha-->beta-tryptase transition.
AB  - Tryptases alpha and beta are trypsin-like serine proteinases expressed in large
      amounts by mast cells. Beta-tryptase is a tetramer that has enzymatic activity,
      but requires heparin binding to maintain functional and structural stability,
      whereas alpha-tryptase has little, if any, enzymatic activity but is a stable
      tetramer in the absence of heparin. As shown previously, these differences can be
      mainly attributed to the different conformations of the 214-220 segment.
      Interestingly, the replacement of Asp216 by Gly, which is present in beta
      tryptase, results in enzymatically active but less stable alpha-tryptase mutants.
      We have solved the crystal structures of both the single (D216G) and the double
      (K192Q/D216G) mutant forms of recombinant human alphaI-tryptase in complex with
      the peptide inhibitor leupeptin, as well as the structure of the non-inhibited
      single mutant. The inhibited mutants exhibited an open functional substrate
      binding site, while in the absence of an inhibitor, the open (beta-tryptase-like)
      and the closed (alpha-tryptase-like) conformations were present simultaneously.
      This shows that both forms are in a two-state equilibrium, which is influenced by
      the residues in the vicinity of the active site and by inhibitor/substrate
      binding. Novel insights regarding the observed stability differences as well as a
      potential proteolytic activity of wild-type alpha-tryptase, which may possess a
      cryptic active site, are discussed.

PMID- 16414070
TI  - The crystal structure of 5'-deoxy-5'-methylthioadenosine phosphorylase II from
      Sulfolobus solfataricus, a thermophilic enzyme stabilized by intramolecular
      disulfide bonds.
AB  - The crystal structure of Sulfolobus solfataricus 5'-deoxy-5'-methylthioadenosine
      phosphorylase II (SsMTAPII) in complex with 5'-deoxy-5'-methylthioadenosine (MTA)
      and sulfate was determined to 1.45A resolution. The hexameric structure of
      SsMTAPII is a dimer-of-trimers with one active site per monomer. The oligomeric
      assembly of the trimer and the monomer topology of SsMTAPII are almost identical
      with trimeric human 5'-deoxy-5'-methylthioadenosine phosphorylase (hMTAP).
      SsMTAPII is the first reported hexameric member in the trimeric class of purine
      nucleoside phosphorylase (PNP) from Archaea. Unlike hMTAP, which is highly
      specific for MTA, SsMTAPII also accepts adenosine as a substrate. The residues at
      the active sites of SsMTAPII and hMTAP are almost identical. The broad substrate
      specificity of SsMTAPII may be due to the flexibility of the C-terminal loop.
      SsMTAPII is extremely thermoactive and thermostable. The three-dimensional
      structure of SsMTAPII suggests that the unique dimer-of-trimers quaternary
      structure, a CXC motif at the C terminus, and two pairs of intrasubunit disulfide
      bridges may play an important role in its thermal stability.

PMID- 16414071
TI  - Phage display reveals multiple contact sites between FhuA, an outer membrane
      receptor of Escherichia coli, and TonB.
AB  - The ferric hydroxamate uptake receptor FhuA from Escherichia coli transports
      siderophores across the outer membrane (OM). TonB-ExbB-ExbD transduces energy
      from the cytoplasmic membrane to the OM by contacts between TonB and OM receptors
      that contain the Ton box, a consensus sequence near the N terminus. Although the
      Ton box is a region of known contact between OM receptors and TonB, our
      biophysical studies established that TonB binds to FhuA through multiple regions
      of interaction. Panning of phage-displayed random peptide libraries (Ph.D.-12,
      Ph.D.-C7C) against TonB identified peptide sequences that specifically interact
      with TonB. Analyses of these sequences using the Receptor Ligand Contacts (RELIC)
      suite of programs revealed clusters of multiply aligned peptides that mapped to
      FhuA. These clusters localized to a continuous periplasm-accessible surface: Ton
      box/switch helix; cork domain/beta1 strand; and periplasmic turn 8. Guided by
      such matches, synthetic oligonucleotides corresponding to DNA sequences identical
      to fhuA were fused to malE; peptides corresponding to the above regions were
      displayed at the N terminus of E.coli maltose-binding protein (MBP). Purified
      FhuA peptides fused to MBP bound specifically to TonB by ELISA. Furthermore, they
      competed with ligand-loaded FhuA for binding to TonB. RELIC also identified
      clusters of multiply aligned peptides corresponding to the Ton box regions in
      BtuB, FepA, and FecA; to periplasmic turn 8 in BtuB and FecA; and to periplasmic
      turns 1 and 2 in FepA. These experimental outcomes identify specific molecular
      contacts made between TonB and OM receptors that extend beyond the well
      characterized Ton box.

PMID- 16414072
TI  - Crystal structure of a glycyl radical enzyme from Archaeoglobus fulgidus.
AB  - We have solved the crystal structure of a PFL2 from Archaeglobus fulgidus at 2.9
      A resolution. Of the three previously solved enzyme structures of glycyl radical
      enzymes, pyruvate formate lyase (PFL), anaerobic ribonucleotide reductase and
      glycerol dehydratase (GD), the last one is clearly most similar to PFL2. We
      observed electron density in the active site of PFL2, which we modelled as
      glycerol. The orientation of the glycerol is different from that in GD, and
      changes in the active site indicate that the actual substrate of PFL2 is bigger
      than a glycerol molecule, but sequence and structural homology suggest that PFL2
      may be a dehydratase. Crystal packing, solution X-ray scattering and
      ultracentrifugation experiments show that PFL2 is tetrameric, unlike other glycyl
      radical enzymes. A.fulgidus is a hyperthermophile and PFL2 appears to be
      stabilized by several factors including an increased number of ion pairs,
      differences in buried charges, a truncated N terminus, anchoring of loops and N
      terminus via salt-bridges, changes in the oligomeric interface and perhaps also
      the higher oligomerization state of the protein.

PMID- 16414073
TI  - The 1.6A X-ray structure of the unusual c-type cytochrome, cytochrome cL, from
      the methylotrophic bacterium Methylobacterium extorquens.
AB  - The structure of cytochrome cL from Methylobacterium extorquens has been
      determined by X-ray crystallography to a resolution of 1.6 A. This unusually
      large, acidic cytochrome is the physiological electron acceptor for the
      quinoprotein methanol dehydrogenase in the periplasm of methylotrophic bacteria.
      Its amino acid sequence is completely different from that of other cytochromes
      but its X-ray structure reveals a core that is typical of class I cytochromes c,
      having alpha-helices folded into a compact structure enclosing the single haem c
      prosthetic group and leaving one edge of the haem exposed. The haem is bound
      through thioether bonds to Cys65 and Cys68, and the fifth ligand to the haem iron
      is provided by His69. Remarkably, the sixth ligand is provided by His112, and not
      by Met109, which had been shown to be the sixth ligand in solution. Cytochrome cL
      is unusual in having a disulphide bridge that tethers the long C-terminal
      extension to the body of the structure. The crystal structure reveals that, close
      to the inner haem propionate, there is tightly bound calcium ion that is likely
      to be involved in stabilization of the redox potential, and that may be important
      in the flow of electrons from reduced pyrroloquinoline quinone in methanol
      dehydrogenase to the haem of cytochrome cL. As predicted, both haem propionates
      are exposed to solvent, accounting for the unusual influence of pH on the redox
      potential of this cytochrome.

PMID- 16414074
TI  - Location of Trp265 in metarhodopsin II: implications for the activation mechanism
      of the visual receptor rhodopsin.
AB  - Isomerization of the 11-cis retinal chromophore in the visual pigment rhodopsin
      is coupled to motion of transmembrane helix H6 and receptor activation. We
      present solid-state magic angle spinning NMR measurements of rhodopsin and the
      metarhodopsin II intermediate that support the proposal that interaction of
      Trp265(6.48) with the retinal chromophore is responsible for stabilizing an
      inactive conformation in the dark, and that motion of the beta-ionone ring allows
      Trp265(6.48) and transmembrane helix H6 to adopt active conformations in the
      light. Two-dimensional dipolar-assisted rotational resonance NMR measurements are
      made between the C19 and C20-methyl groups of the retinal and uniformly 13C
      labeled Trp265(6.48). The retinal C20-Trp265(6.48) contact present in the dark
      state of rhodopsin is lost in metarhodopsin II, and a new contact is formed with
      the C19 methyl group. We have previously shown that the retinal translates 4-5 A
      toward H5 in metarhodopsin II. This motion, in conjunction with the Trp-C19
      contact, implies that the Trp265(6.48) side-chain moves significantly upon
      rhodopsin activation. NMR measurements also show that a packing interaction in
      rhodopsin between Trp265(6.48) and Gly121(3.36) is lost in metarhodopsin II,
      consistent with H6 motion away from H3. However, a close contact between
      Gly120(3.35) on H3 and Met86(2.53) on H2 is observed in both rhodopsin and
      metarhodopsin II, suggesting that H3 does not change orientation significantly
      upon receptor activation.

PMID- 16414075
TI  - Crystal structure of the polyketide cyclase AknH with bound substrate and product
      analogue: implications for catalytic mechanism and product stereoselectivity.
AB  - AknH is a small polyketide cyclase that catalyses the closure of the fourth
      carbon ring in aclacinomycin biosynthesis in Streptomyces galilaeus, converting
      aklanonic acid methyl ester to aklaviketone. The crystal structure analysis of
      this enzyme, in complex with substrate and product analogue, showed that it is
      closely related in fold and mechanism to the polyketide cyclase SnoaL that
      catalyses the corresponding reaction in the biosynthesis of nogalamycin.
      Similarity is also apparent at a functional level as AknH can convert nogalonic
      acid methyl ester, the natural substrate of SnoaL, to auraviketone in vitro and
      in constructs in vivo. Despite the conserved structural and mechanistic features
      between these enzymes, the reaction products of AknH and SnoaL are
      stereochemically distinct. Supplied with the same substrate, AknH yields a C9-R
      product, like most members of this family of polyketide cyclases, whereas the
      product of SnoaL has the opposite C9-S stereochemistry. A comparison of high
      resolution crystal structures of the two enzymes combined with in vitro
      mutagenesis studies revealed two critical amino acid substitutions in the active
      sites, which contribute to product stereoselectivity in AknH. Replacement of
      residues Tyr15 and Asn51 of AknH, located in the vicinity of the main catalytic
      residue Asp121, by their SnoaL counter-parts phenylalanine and leucine,
      respectively, results in a complete loss of product stereoselectivity.

PMID- 16414076
TI  - Novel mutation of neurofibromatosis type 1 in a patient with cerebral
      vasculopathy and fatal ischemic stroke.
AB  - Vascular lesions are infrequently recognized as manifestations of
      neurofibromatosis 1 (NF1), but they can produce serious complications and
      contribute to mortality at younger ages. Here we report the case of a young
      female patient with NF1 who suffered from a fatal middle cerebral artery (MCA)
      infarct. In addition to the MCA infarct, head MRI also disclosed old infarcts at
      bilateral cerebella and multiple intracranial arterial steno-occlusions. Stroke
      related to NF1 cerebral vasculopathy was highly suggested after other diseases
      were excluded. Additionally, genetic analysis of the patient identified a novel
      mutation at the splicing donor site, c. 2,409+2T>G that resulted in a splicing
      aberration.

PMID- 16414078
TI  - Peripheral neuropathies caused by mutations in the myelin protein zero.
AB  - Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by mutations in the major
      PNS myelin protein myelin protein zero (MPZ). MPZ is a member of the
      immunoglobulin supergene family and functions as an adhesion molecule helping to
      mediate compaction of PNS myelin. Mutations in MPZ appear to either disrupt
      myelination during development, leading to severe early onset neuropathies, or to
      disrupt axo-glial interactions leading to late onset neuropathies in adulthood.
      Identifying molecular pathways involved in early and late onset CMT1B will be
      crucial to understand how MPZ mutations cause CMT1B so that rational therapies
      for both early and late onset neuropathies can be developed.

PMID- 16414077
TI  - Antimyoclonic effect of levetiracetam in MERRF syndrome.
AB  - The treatment of progressive myoclonic epilepsy (PME) is largely empirical, even
      though valproic acid (VPA) is usually considered the drug of first choice.
      However, VPA should be used with caution in PME due to mitochondrial dysfunction,
      i.e. in MERRF (myoclonic epilepsy with ragged red fibers) syndrome, because of
      its interaction with mitochondrial respiration and metabolism. Levetiracetam
      (LEV) treatment was started in combination with VPA in a patient with typical
      clinical, histological, and biochemical features of MERRF due to a mutation on
      the tRNA of Phenilalanine gene. The average myoclonus score improved
      dramatically, as well as the quality of life and no side effects were observed,
      even after having withdrawn VPA. LEV may benefit myoclonus in PME of
      mitochondrial origin without altering mitochondrial function, and it could be
      considered the drug of first choice for the treatment of myoclonus in MERRF.

PMID- 16414079
TI  - Prey-predator system with parental care for predators.
AB  - A stage structure is incorporated into a prey-predator model in which predators
      are split into immature predators and mature predators. It is assumed that
      immature predators are raised by their parents in the sense that they cannot
      catch the prey and their foods are provided by parents. Further, it is assumed
      that the maturation rate of immature predators is a function of the food
      availability for one immature individual. It is found that the model admits
      periodic solutions which are produced from the stage structure. Further, it is
      shown that two stability switches of positive equilibria may occur due to the
      transition rate incorporating the influence of nutrient, and that the enrichment
      of adult predators may lead to the catastrophe of the ecological system.

PMID- 16414080
TI  - Proteomics analysis of the actions of grape seed extract in rat brain:
      technological and biological implications for the study of the actions of
      psychoactive compounds.
AB  - Grape seed extract (GSE) is a commonly available dietary supplement taken for the
      anti-oxidant activity that's attributed to its proanthocyanidin (oligomers of
      monomeric polyphenols) content. Similar polyphenol-enriched preparations from
      blueberries and soy have shown protection against ovariectomy-induced or age
      related cognitive deficits, suggesting that the molecular changes induced by
      these polyphenol preparations correlated with behavioral benefit. We hypothesized
      that ingestion of polyphenol-enriched preparations such as GSE would be
      manifested as protein changes that would be consistent with neuroprotection.
      Proteomics technology, namely 2D gel electrophoresis and mass spectrometry,
      identified quantitative changes in specific proteins induced in adult rat brain
      following ingestion of a powdered preparation of GSE. As recently reported
      [Deshane, J., Chaves, L., Sarikonda, K.V., Isbell, S., Wilson, L., Kirk, M.,
      Grubbs, C., Barnes, S., Meleth, S. and Kim, H., 2004. Proteomics analysis of rat
      brain protein modulations by grape seed extract. Journal of Agricultural and Food
      Chemistry 52, 7872-7883.], the direction of change for the majority of the
      affected proteins was opposite to the direction the proteins were changed in
      either Alzheimer disease or in transgenic mouse models of dementia. A
      conservative conclusion is that GSE has neuroprotective activity, by affecting
      specific proteins in particular ways. In this chapter, elements of proteomics
      type analysis are discussed that demonstrate the power of the technology to
      enable discovery of proteins involved in the response of the brain to a stimulus
      whether it be a dietary supplement, or a psychoactive drug. The fact that GSE
      affects proteins implicated in cognitive disorders suggests moreover that GSE may
      have impact on the actions of psychoactive drugs by maintaining an overall
      viability of the nervous system.

PMID- 16414081
TI  - No response of plasma substance P, but delayed increase of interleukin-1 receptor
      antagonist to acute psychosocial stress.
AB  - Psychosocial stress has been shown to induce inflammatory reactions, followed by
      the release of immunosuppressive glucocorticoids. This may be mediated by
      catecholamines or other stress reactive substances such as neuropeptides or
      cytokines. We here set out to explore the effects of acute psychosocial stress on
      plasma levels of substance P (SP), a possible mediator of stress-induced
      inflammatory reactions, and interleukin-1 receptor antagonist (IL-1ra). Twelve
      healthy male subjects (mean age 27 yrs.) were subjected to the psychosocial
      stress test "Trier Social Stress Test" (TSST) and a resting control condition.
      Blood and saliva samples were taken before, as well as 1, 20, 45, and 90 min
      after TSST or rest, respectively. Salivary cortisol and plasma SP and IL-1ra were
      measured using immunoassays, salivary alpha-amylase (sAA) was measured by an
      enzyme kinetic method, and plasma epinephrine (E) and norepinephrine (NE) were
      measured by HPLC. The TSST induced immediate increases of E, NE, and sAA, and a
      delayed increase of free cortisol. Plasma IL-1ra showed an even further delayed
      peak at 90 min after stress. Plasma levels of SP did not respond to stress. No
      significant associations between changes of stress hormones and IL-1ra or SP were
      found. We conclude that substance P, epinephrine, and norepinephrine are probably
      not involved in mediating peripheral inflammation following psychosocial stress,
      at least with respect to IL-1ra. Further studies have to reveal the mechanisms
      involved in the stress-induced up regulation of IL-1ra.

PMID- 16414082
TI  - Traditional nonsense.

PMID- 16414083
TI  - Do homeopathic drugs affect microcirculation in vertigo?

PMID- 16414084
TI  - Human endothelial cells express NOD2/CARD15 and increase IL-6 secretion in
      response to muramyl dipeptide.
AB  - Mutations in the human NOD2/CARD15 gene cause Blau syndrome, an autoinflammatory
      disorder involving the joints, skin and eyes. Insights into the mechanism of this
      association may be gained by a further understanding of where NOD2 is expressed.
      The objective of this study was to analyze ocular endothelial cells for NOD2
      expression. Human ocular tissue was analyzed by immunohistology using anti-NOD2
      antisera. RNA isolated from iris, choroid and endothelial cell lines was analyzed
      by reverse transcription-PCR and real-time quantitative PCR. Gene regulation was
      studied by treating endothelial cells with TNF-alpha and IFN-gamma. Functional
      responses were assessed by measuring IL-6 release from endothelial cells treated
      with muramyl dipeptide (MDP), synthetic lipopeptide (Pam3CSK4) and
      lipopolysaccharide (LPS). Immunohistological analysis revealed staining of
      endothelial cells in the uveal tract. NOD2 expression was detected in primary
      ocular endothelial cell cultures, and levels increased in response to
      inflammatory cytokines. Endothelial cells from choroid demonstrated enhanced
      release of IL-6 in response to MDP, and synergy was observed following treatment
      with MDP and either Pam3CSK4 or LPS. The observations that endothelial cells
      express NOD2, upregulate NOD2 in response to stimuli known to promote NOD2
      expression and show synergistic cytokine responses to MDP and TLR ligands
      previously shown to be mediated by NOD2 are informative since they may be
      relevant to pathogenic mechanisms leading to the spectrum of inflammation seen in
      Blau syndrome.

PMID- 16414085
TI  - Critical time window of hedgehog-dependent angiogenesis in murine yolk sac.
AB  - Hedgehog family was reported to be involved in murine yolk sac angiogenesis.
      However, it has not been clarified whether impaired angiogenesis under hedgehog
      signaling blockade is attributable to true defect in angiogenic process or just a
      sequel of earlier vasculogenic abnormalities. In the present study, we examined
      the effects of stage-specific inhibition of hedgehog cascade on vascular
      morphogenesis by applying cyclopamine or jervine to culture media of whole embryo
      culture system from embryonic days 8.0 until 9.5. Whole-mount immunostaining
      revealed that cyclopamine or jervine treatment in a narrow time window impaired
      angiogenic remodeling such as ramification into large and small branches and
      pericyte recruitment, although vasculogenesis was grossly normal. Molecular
      analyses suggest that indian hedgehog in the yolk sac endoderm regulates the
      induction of VEGF, Flk-1 and Notch-1. Our results indicate that hedgehog
      signaling is indispensable for mouse yolk sac angiogenesis, even when
      vasculogenesis is not perturbed.

PMID- 16414086
TI  - Bystander-mediated genomic instability after high LET radiation in murine primary
      haemopoietic stem cells.
AB  - Communication between irradiated and unirradiated (bystander) cells can result in
      responses in unirradiated cells that are similar to responses in their irradiated
      counterparts. The purpose of the current experiment was to test the hypothesis
      that bystander responses will be similarly induced in primary murine stem cells
      under different cell culture conditions. The experimental systems used here, co
      culture and media transfer, are similar in that they both restrict communication
      between irradiated and bystander cells to media borne factors, but are distinct
      in that with the media transfer technique, cells can only communicate after
      irradiation, and with co-culture, cells can communication before, during and
      after irradiation. In this set of parallel experiments, cell type, biological
      endpoint, and radiation quality and dose, were kept constant. In both
      experimental systems, clonogenic survival was significantly decreased in all
      groups, whether irradiated or bystander, suggesting a substantial contribution of
      bystander effects (BE) to cell killing. Genomic instability (GI) was induced
      under all radiation and bystander conditions in both experiments, including a
      situation where unirradiated cells were incubated with media that had been
      conditioned for 24h with irradiated cells. The appearance of delayed aberrations
      (genomic instability) 10-13 population doublings after irradiation was similar to
      the level of initial chromosomal damage, suggesting that the bystander factor is
      able to induce chromosomal alterations soon after irradiation. Whether these
      early alterations are related to those observed at later timepoints remains
      unknown. These results suggest that genomic instability may be significantly
      induced in a bystander cell population whether or not cells communicate during
      irradiation.

PMID- 16414087
TI  - Adaptive mutations in Salmonella typhimurium phenotypic of purR super-repression.
AB  - Under non-lethal selective conditions, a non-dividing or very slowly dividing
      microbial population gives rise to mutations that relieve selective pressures.
      This process is described as adaptive mutation. Salmonella typhimurium strain 5
      28 has been used as a system for studying adaptive mutations in the chromosomal
      regulatory gene purR and its target, the purD operator. When this strain is
      plated on a minimal lactose medium, no apparent growth of parent lawn is
      observed, yet the revertant colonies accumulate over a period of time. Analysis
      of the purR mutational spectra showed that the frequencies of transitions and
      transversions were not significantly different among the growth-dependent and
      adaptive mutations. But the frequencies for five kinds of -1 frameshifts were
      significantly different between the growth-dependent and adaptive types. Among
      the growth-dependent mutations, most one-base deletions occurred in non-iterated
      bases and were distributed randomly. Among adaptive mutations, the frequency of
      one-base deletions in small mononucleotide repeats was higher and mutations were
      concentrated at three hotspots. One-base deletion in small mononucleotide repeats
      are generally believed to result from DNA polymerase slippage errors, which are
      not corrected by DNA repair machinery. We further investigated the role of DNA
      repair on adaptive mutation. Our results showed that the mismatch repair (MMR)
      might function less efficiently during adaptive mutation. However, DNA oxidative
      damage repair seemed no less effective in correcting errors under selective
      pressures than during non-selective growth.

PMID- 16414089
TI  - Neoplastic transformation in vitro by low doses of ionizing radiation: role of
      adaptive response and bystander effects.
AB  - The shape of the dose-response curve for cancer induction by low doses of
      ionizing radiation is of critical importance to the assessment of cancer risk at
      such doses. Epidemiologic analyses are limited by sensitivity to doses typically
      greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the
      examination of lower doses using cancer-relevant endpoints. One such endpoint is
      neoplastic transformation in vitro. It is known that this endpoint is responsive
      to both adaptive response and bystander effects. The relative balance of these
      processes is likely to play an important role in determining the shape of the
      dose-response curve at low doses. A factor that may influence this balance is
      cell density at time of irradiation. The findings reported in this paper indicate
      that the transformation suppressive effect of low doses previously seen following
      irradiation of sub-confluent cultures, and attributed to an adaptive response, is
      reduced for irradiated confluent cultures. However, even under these conditions
      designed to optimize the role of bystander effects the data do not fit a linear
      no-threshold model and are still consistent with the notion of a threshold dose
      for neoplastic transformation in vitro by low LET radiation.

PMID- 16414088
TI  - Radiation-induced bystander effects and the DNA paradigm: an "out of field"
      perspective.
AB  - Over the past 20 years there has been increasing evidence that cells and the
      progeny of cells surviving a very low dose of ionizing radiation [micro-mGy] can
      exhibit a wide range of non-monotonic effects such as adaptive responses, low
      dose hypersensitivity and other delayed effects. These effects are inconsistent
      with the expected dose-response, when based on extrapolation of high dose data
      and cast doubt on the reliability of extrapolating from high dose data to predict
      low dose effects. Recently the cause of many of these effects has been
      tentatively ascribed to so-called "bystander effects". These are effects that
      occur in cells not directly hit by an ionizing track but which are influenced by
      signals from irradiated cells and are thus highly relevant in situations where
      the dose is very low. Not all bystander effects may be deleterious although most
      endpoints measured involve cell damage or death. In this commentary, we consider
      how these effects impact the historical central dogma of radiobiology and
      radiation protection, which is that DNA double strand breaks are the primary
      radiation-induced lesion which can be quantifiably related to received dose and
      which determine the probability that a cancer will result from a radiation
      exposure. We explore the low dose issues and the evidence and conclude that in
      the very low dose region, the primary determinant of radiation exposure outcome
      is the genetic and epigenetic background of the individual and not solely the
      dose. What this does is to dissociate dose from effect as a quantitative
      relationship, but it does not necessarily mean that the effect is ultimately
      unrelated to DNA damage. The fundamental thesis we present is that at low doses
      fundamentally different mechanisms underlie radiation action and that at these
      doses, effect is not quantitatively related to dose.

PMID- 16414090
TI  - A natural products chemist looks at the bystander effect!
AB  - The bystander effect is a process whereby the medium in which cells are
      irradiated at very low levels is presumed to contain a "low molecular weight"
      entity that will induce cell death and/or genetic changes in fresh mammalian
      cells when they are incubated in the medium. Following discussions at a recent
      meeting in McMaster University, suggestions are made in this paper as to the
      possibility for the "entity" to be nitric oxide and recommendations are given as
      to methods that will permit a systematic (bio)chemical search to be performed in
      order to identify the "activator" and prove/disprove the hypothesis.

PMID- 16414091
TI  - What role for DNA damage and repair in the bystander response?
AB  - The radiation-induced bystander effect challenges the accepted paradigm of direct
      DNA damage in response to energy deposition driving the biological consequences
      of radiation exposure. With the bystander response, cells which have not been
      directly exposed to radiation respond to their neighbours being targeted. In our
      own studies we have used novel targeted microbeam approaches to specifically
      irradiate parts of individual cells within a population to quantify the bystander
      response and obtain mechanistic information. Using this approach it has become
      clear that energy deposited by radiation in nuclear DNA is not required to
      trigger the effect, with cytoplasmic irradiation required. Irradiated cells also
      trigger a bystander response regardless of whether they themselves live or die,
      suggesting that the phenotype of the targeted cell is not a determining factor.
      Despite this however, a range of evidence has shown that repair status is
      important for dealing with the consequences of a bystander signal. Importantly,
      repair processes involved in the processing of dsb appear to be involved
      suggesting that the bystander response involves the delayed or indirect
      production of dsb-type lesions in bystander cells. Whether these are infact true
      dsb or complexes of oxidised bases in combination with strand breaks and the
      mechanisms for their formation, remains to be elucidated.

PMID- 16414092
TI  - Radiation and the regulatory landscape of neo2-Darwinism.
AB  - Several recently revealed features of eukaryotic genomes were not predicted by
      earlier evolutionary paradigms, including the relatively small number of genes,
      the very large amounts of non-functional code and its quarantine in
      heterochromatin, the remarkable conservation of many functionally important genes
      across relatively enormous phylogenetic distances, and the prevalence of extra
      genomic information associated with chromatin structure and histone proteins. All
      of these emphasize a paramount role for regulatory evolution, which is further
      reinforced by recent perspectives highlighting even higher-order regulation
      governing epigenetics and development (EVO-DEVO). Modern neo2-Darwinism, with its
      emphasis on regulatory mechanisms and regulatory evolution provides new vision
      for understanding radiation biology, particularly because free radicals and redox
      states are central to many regulatory mechanisms and free radicals generated by
      radiation mimic and amplify endogenous signalling. This paper explores some of
      these aspects and their implications for low-dose radiation biology.

PMID- 16414093
TI  - Bystander effect: biological endpoints and microarray analysis.
AB  - In cell populations exposed to ionizing radiation, the biological effects occur
      in a much larger proportion of cells than are estimated to be traversed by
      radiation. It has been suggested that irradiated cells are capable of providing
      signals to the neighboring unirradiated cells resulting in damage to these cells.
      This phenomenon is termed the bystander effect. The bystander effect induces
      persistent, long-term, transmissible changes that result in delayed death and
      neoplastic transformation. Because the bystander effect is relevant to
      carcinogenesis, it could have significant implications for risk estimation for
      radiation exposure. The nature of the bystander effect signal and how it impacts
      the unirradiated cells remains to be elucidated. Examination of the changes in
      gene expression could provide clues to understanding the bystander effect and
      could define the signaling pathways involved in sustaining damage to these cells.
      The microarray technology serves as a tool to gain insight into the molecular
      pathways leading to bystander effect. Using medium from irradiated normal human
      diploid lung fibroblasts as a model system we examined gene expression
      alterations in bystander cells. The microarray data revealed that the radiation
      induced gene expression profile in irradiated cells is different from
      unirradiated bystander cells suggesting that the pathways leading to biological
      effects in the bystander cells are different from the directly irradiated cells.
      The genes known to be responsive to ionizing radiation were observed in
      irradiated cells. Several genes were upregulated in cells receiving media from
      irradiated cells. Surprisingly no genes were found to be downregulated in these
      cells. A number of genes belonging to extracellular signaling, growth factors and
      several receptors were identified in bystander cells. Interestingly 15 genes
      involved in the cell communication processes were found to be upregulated. The
      induction of receptors and the cell communication processes in bystander cells
      receiving media from irradiated cells supports the active involvement of these
      processes in inducing bystander effect.

PMID- 16414094
TI  - Perception of the vertical in patients with right hemispheric lesion: effect of
      galvanic vestibular stimulation.
AB  - Patients with right-brain injury present, more frequently in the acute phase,
      with a deviation of the subjective vertical (SV) contralateral to the lesion. The
      aim of this study was to investigate the influence of galvanic vestibular
      stimulation (GVS) on this disorder. Twelve patients presenting with a right
      hemispheric lesion, seven with neglect (N+) and five without (N-) were compared
      to eight control subjects. They had to orient vertically a luminous rod in
      darkness, in three galvanic stimulation (1.5 mA) conditions: cathode left,
      cathode right and no stimulation (baseline). Without stimulation, the patients'
      SV, and especially that of N+, showed an anticlockwise deviation. In comparison
      with baseline values, GVS induced a deviation toward the side opposite to the
      cathode in the three groups. In the patients, the deviation was of larger
      amplitude and appeared greater for left than for right cathodic stimulation. In
      conclusion, we showed an influence of vestibular stimulation on the SV of right
      brain-injured patients, especially when spatial neglect was present. As left
      cathodic stimulation can reduce the SV deviation associated with spatial neglect,
      such a tool could be introduced in rehabilitation.

PMID- 16414096
TI  - Subthreshold features of visual objects: unseen but not unbound.
AB  - The object is a basic unit that is thought to organize the way in which we
      perceive and think about the world. According to theories of object-based
      attention, perception of unified objects depends on the binding together of the
      disparate features of each object via attention. Here we show that a visual
      feature that is not consciously perceived is nonetheless modulated by object
      based attention: the influence of a subthreshold motion signal (prime) on
      subsequent motion perception depended critically on whether it was associated
      with the attended object or another, spatially overlapping object. These results
      show that invisibly weak features of attended objects are not lost, but are
      organized by and selected together with the object by attention.

PMID- 16414095
TI  - Bancroftian filariasis: effect of repeated treatment with diethylcarbamazine and
      albendazole on microfilaraemia, antigenaemia and antifilarial antibodies.
AB  - Diethylcarbamazine/albendazole (DEC/ALB) therapy is widely used in mass drug
      administration (MDA) programmes aimed at eliminating lymphatic filariasis. We
      studied the effects of repeated annual treatments with DEC/ALB on Wuchereria
      bancrofti microfilaraemia, filarial antigenaemia and IgG4 antibodies to Bm14
      antigen. Fifty-seven subjects with asymptomatic microfilaraemia were treated with
      one or seven daily doses of DEC/ALB at time zero. All subjects were re-treated
      with single-dose DEC/ALB 12, 24 and 36 months later. The two treatment groups had
      comparable pre-treatment microfilaria counts. Multidose treatment cleared
      microfilaraemia more effectively than single-dose treatment. Filarial antigen
      levels decreased equally in both treatment groups. Total antigen clearance was
      observed in 29.6%, 52.0%, 63.6% and 79.5% of subjects at 12, 24, 36 and 48
      months. These clearance rates are much higher than those observed in prior
      treatment trials with DEC or ivermectin. Antibody levels increased 4 weeks after
      treatment and then slowly decreased in most subjects. Antibody tests turned
      negative in 20%, 35%, 39.4% and 52.5% of treated subjects at 12, 24, 36 and 48
      months post treatment. These results show that the studied parameters decline at
      different rates and to differing degrees following DEC/ALB treatment. These
      findings have important implications regarding strategies for monitoring the
      effects of MDA in populations.

PMID- 16414097
TI  - Level and mechanisms of perceptual learning: learning first-order luminance and
      second-order texture objects.
AB  - Perceptual learning is an improvement in perceptual task performance reflecting
      plasticity in the perceptual system. Practice effects were studied in two object
      orientation tasks: a first order, luminance object task and a second-order,
      texture object task. Perceptual learning was small or absent in the first-order
      task, but consistently occurred for the second-order (texture) task, where it was
      limited to improvements in low external noise conditions, or stimulus enhancement
      [Dosher, B., & Lu, Z. -L. (1998). Perceptual learning reflects external noise
      filtering and internal noise reduction through channel reweighting. Proceedings
      of the National Academy of Sciences of the United States of America, 95 (23)
      13988-13993; Dosher, B., & Lu, Z. -L. (1999). Mechanisms of perceptual learning.
      Vision Research, 39 (19) 3197-3221], analogous to attention effects in first- and
      second-order motion processing [Lu, Z. -L., Liu, C. Q., & Dosher, B. (2000).
      Attention mechanisms for multi-location first- and second-order motion
      perception. Vision Research, 40 (2) 173-186]. Perceptual learning affected the
      later, post-rectification, stages of perceptual analysis, possibly localized at
      V2 or above. It serves to amplify the stimulus relative to limiting internal
      noise for intrinsically noisy representations of second-order stimuli.

PMID- 16414098
TI  - Treatment of cork boiling wastewater using chemical oxidation and biodegradation.
AB  - Three cultures were enriched from cork boiling wastewater using tannic acid as
      the selective carbon substrate, at 25 degrees C and pH 7.2, 25 degrees C and pH
      4.7 and 50 degrees C and pH 4.7. The enrichment culture obtained at neutral pH
      was composed of five culturable isolates, whereas from each acidic enrichment two
      bacterial strains were isolated. Mesophilic isolates were Gram negative bacteria
      belonging to the genera Klebsiella, Pseudomonas, Stenotrophomonas and
      Burkholderia. Thermophilic isolates were members of the genus Bacillus. Despite
      the capability of the enrichment cultures to use tannic acid as single carbon and
      energy source, those cultures were unable to reduce the total polyphenols or the
      total organic carbon content of cork boiling wastewater. In order to increase the
      bioavailability of the organic carbon in cork boiling wastewater, biodegradation
      was preceded by Fenton oxidation. It was demonstrated that the combined process,
      using small amounts of Fenton reagents and biodegradative inoculum added almost
      simultaneously to cork boiling wastewater, leads to TOC reductions of more than
      90%.

PMID- 16414099
TI  - Associations between shell strength, shell morphology and heavy metals in the
      land snail Cepaea nemoralis (Gastropoda, Helicidae).
AB  - In snails there is an intimate relation between shell size, thickness, strength
      and calcium content that may be influenced by environmental factors such as
      predation and heavy metal pollution. The snail Cepaea nemoralis shows variability
      for shell colour and banding pattern, and frequencies of colour morphs are highly
      variable in natural populations. We used C. nemoralis to investigate (i) the
      relations between shell morphology, shell Ca and heavy metal content (Cd, Cr, Pb,
      Zn), and shell strength, (ii) differences in shell morphology and shell strength
      among localities and yellow and pink shells and (iii) whether snails from
      polluted sites show increased levels of heavy metals in their shell. Larger
      shells were heavier, thicker, needed a higher force to be crushed but did not
      have a higher Ca concentration. Cd and Zn concentrations were higher in shells
      from polluted plots compared to shells from unpolluted plots but Ca levels in the
      shell were comparable among plots. Zn concentration was negatively correlated
      with shell traits. Although there was substantial variation in shell strength,
      thickness and dry weight among localities, none of the shell traits differed
      between individuals from polluted and reference plots nor between colour morphs.
      Our results suggest that the effect of heavy metal pollution on shell strength
      and morphology is limited in the investigated populations.

PMID- 16414100
TI  - A stable lead isotopic investigation of the use of sycamore tree rings as a
      historical biomonitor of environmental lead contamination.
AB  - The validity of the use of sycamore (Acer pseudoplatanus) tree-rings for the
      reconstruction of atmospheric lead pollution histories was investigated. Tree
      cores spanning 1892-2003 were collected from several sycamores from the eastern
      shore of Loch Lomond, Scotland, an area with no local point sources of lead
      emission. The lead concentration and 206Pb/207Pb profiles of the Loch Lomond
      region cores were compared with corresponding data for the 210Pb-dated loch
      sediment, and also with data for moss of known age from a Scottish herbarium
      collection. Two of the seven sycamore cores showed the same lead concentration
      trend as the lead flux to the loch, the rest having no similarity to either each
      other or the loch sediment record. Two further sycamore cores showed some
      similarity in their temporal 206Pb/207Pb trends to those seen in the sediment and
      moss records, but only in part of their profiles, whilst the 206Pb/207Pb ratios
      of the other sycamore cores remained relatively unchanged for the majority of the
      time covered, or exhibited an opposite trend. The 206Pb/207Pb ratios of the tree
      cores were also mostly higher than those of the previously established records
      for any given time period. Tree cores covering 1878-2002 were also collected
      along transects from Wanlockhead and Tyndrum, two areas of former lead mining and
      smelting associated with distinct 206Pb/207Pb ratios of 1.170 and 1.144,
      respectively. The Wanlockhead tree cores exhibited a generally decreasing trend
      in lead concentration with both time and distance from the lead mine. The
      characteristic 206Pb/207Pb ratio of 1.170 was observed in samples close to the
      mine but a decrease in the influence of the mine-derived lead was observed in
      more distant samples. The tree sampled at Tyndrum showed elevated lead
      concentrations, which decreased with time, and a fairly constant 206Pb/207Pb
      ratio of 1.15 reflecting input from the mine, features not observed in any other
      trees along the transect. Overall the data suggest that sycamore tree-ring
      analysis is an unsuitable method for obtaining records of historical lead
      deposition in areas with no large local lead input, although it can reveal some
      information about the temporal and spatial influence of point source emitters.
      The unsuitability probably arises from the number of active annual rings in a
      single year, the post-uptake radial translocation of elements, the relative
      importance of the different routes of uptake, and the soil depth(s) from which
      trees draw nutrients.

PMID- 16414101
TI  - Isolated prolonged activated partial thromboplastin time in an asymptomatic
      patient: Fletcher factor deficiency.

PMID- 16414102
TI  - Diagnostic value of a negative single complete compression ultrasound of the
      lower limbs to exclude the diagnosis of deep venous thrombosis in pregnant or
      postpartum women: a retrospective hospital-based study.
AB  - OBJECTIVE: We aimed at determining whether a negative single complete compression
      ultrasonography (CUS) of the lower limbs veins is a safe and accurate diagnostic
      method to rule out the diagnosis of deep venous thrombosis in pregnant and early
      postpartum women. DESIGN: Hospital-based retrospective study. SETTING: The
      gynaecology and vascular ultrasound units of three general hospitals in western
      France. PATIENTS: We identified from the hospitals databases all pregnant or up
      to three months postpartum women who underwent CUS for a suspicion of deep venous
      thrombosis between January 2002 and December 2004. METHODS: Questionnaires were
      sent to all women with a negative CUS. Their medical records were also checked.
      MAIN OUTCOME MEASURES: We assessed the three-month thromboembolic risk and its
      95% percent confidence interval in women left untreated on the basis of a
      negative single complete CUS of the lower limbs. RESULTS: During the study
      period, 162 pregnant or postpartum women underwent CUS for a suspicion of deep
      venous thrombosis. It was positive in 44 (27%). The 118 women who had a negative
      CUS were sent the questionnaire. Information about the three-month follow-up was
      found for 107 patients (91%). None of them experienced a thromboembolic event
      during follow-up: 0.0% (95% CI: 0.0-3.6). CONCLUSIONS: Single complete CUS of
      lower limbs veins appears to be a safe method to rule out the diagnosis of deep
      venous thrombosis in pregnant or early postpartum women. This has to be confirmed
      by a prospective management study with a formal follow-up.

PMID- 16414104
TI  - Immunohistochemical labelling of components of the endoneurial extracellular
      matrix of intact and rhizotomized dorsal and ventral spinal roots of the rat--a
      quantitative evaluation using image analysis.
AB  - The endoneurial extracellular matrix (ECM) molecules are involved in cell
      signalling during nervous system development and regeneration. Quantitative
      differences of immunofluorescence labelling for chondroitin sulfate proteoglycan
      (CSPG), fibronectin (FN), tenascin-C (TN-C), and thrombospondin (TSP) were
      evaluated in intact rat dorsal and ventral roots and dorsal and ventral roots 2
      and 4 weeks after rhizotomy using image analysis. The distal stumps of spinal
      roots displayed increased immunolabelling for the molecules with higher
      immunofluorescence in dorsal than in ventral roots up to 2 weeks from
      transection. Four weeks after rhizotomy, the immunoreactivity for CSPG, TN-C and
      TSP decreased in dorsal and increased in ventral root stumps, although a higher
      level of immunofluorescence for FN remained in both dorsal and ventral root
      stumps 4 weeks after injury in comparison to 2 weeks after injury. We suggest
      that the amount of some ECM molecules changed differentially 2 and 4 weeks after
      rhizotomy to create an appropriate environment in the endoneurium for early and
      later regrowth of sensory and motor axons. The results presented here are the
      first report of differences between the endoneurial ECM content of damaged
      afferent and motor nerve fibers. In addition, the immunohistochemical detection
      of individual ECM molecules indicated that final extrinsic conditions stimulating
      the regrowth of regenerating axons probably arise from a balance of both growth
      promoting and -inhibiting molecules in the endoneurium.

PMID- 16414103
TI  - Analysis of unconventional approaches for the rapid detection of surface lectin
      binding ligands on human cell lines.
AB  - For over a decade our laboratory has developed and used a novel histochemical
      assay using derivatized agarose beads to examine the surface properties of
      various cell types. Most recently, we have used this assay to examine lectin
      binding ligands on two human cell types, CCL-220, a colon cancer cell line, and
      CRL-1459, a non-cancer colon cell line. We found that CCL-220 cells bound
      specific lectins better than CRL-1459, and this information was used to test for
      possible differential toxicity of these lectins in culture, as a possible
      approach in the design of more specific anti-cancer drugs. Although we have
      examined the validity of the bead-binding assay in sea urchin cell systems, we
      have not previously validated this technique for mammalian cells. Here the
      binding results of the bead assay are compared with conventional fluorescence
      assays, using lectins from three species (Triticum vulgaris, Phaseolus vulgaris,
      and Lens culinaris) on the two colon cell lines. These lectins were chosen
      because they seemed to interact with the two cell lines differently. Binding
      results obtained using both assays were compared for frozen, thawed and fixed;
      cultured and fixed; and live cells. Both qualitative and quantitative
      fluorescence results generally correlated with those using the bead assay.
      Similar results were also obtained with all of the three different cell
      preparation protocols. The fluorescence assay was able to detect lower lectin
      binding ligand levels than the bead assay, while the bead assay, because it can
      so rapidly detect cells with large numbers of lectin binding ligands, is ideal
      for initial screening studies that seek to identify cells that are rich in
      surface binders for specific molecules. The direct use of frozen, thawed and
      fixed cells allows rapid mass screening for surface molecules, without the
      requirement for costly and time consuming cell culture.

PMID- 16414105
TI  - Megestrol acetate induced hypoadrenalism with cushingoid phenotype in endometrial
      cancer.

PMID- 16414106
TI  - Ability of induced corpora lutea to maintain pregnancy from the third month of
      gestation to term in cattle.
AB  - The local relationship between the pregnant uterine horn and the CL during
      maternal recognition of pregnancy is well-documented. It continues beyond that
      time; pregnancies were maintained in lutectomized cows when CL were induced on
      the ovary ipsilateral, but not contralateral, to the uterine horn of pregnancy
      during Days 28-53. This study evaluated factors affecting maintenance of
      pregnancy by CL induced after Day 53, in lutectomized cows that had received
      exogenous progesterone from Day 29 to 15 days after induction of a CL. Twenty
      four suckled beef cows were lutectomized on Day 29 of gestation; pregnancy was
      maintained with progesterone from two controlled internal drug releasing (CIDR)
      inserts, exchanged every 5 days. Beginning on Day 53, ovaries and viability of
      pregnancy were evaluated by ultrasonography every 5 days. When a follicle >or=10
      mm in diameter was present ipsilateral to the fetus, each cow received 1,000 IU
      of hCG. Following induction of a CL (20 of 24), progesterone was reduced to a
      single CIDR for 5 days, then removed. Retention of pregnancy was confirmed by
      rectal palpation and calving. Cows with induced CL maintained pregnancy to term,
      including four with the CL contralateral to the fetus. Three cows failed to form
      normal CL by Day 98 and lost pregnancy after removal of exogenous progesterone.
      One cow that did not respond to hCG lost pregnancy during exogenous progesterone.
      In conclusion, CL induced after Day 53 maintained pregnancy to term, even when
      induced contralateral to the pregnant uterine horn.

PMID- 16414107
TI  - Systematic factor optimization for sperm cryopreservation of tetraploid Pacific
      oysters, Crassostrea gigas.
AB  - The availability of tetraploid Pacific oysters provides a unique opportunity for
      comparative studies of sperm cryopreservation between diploids and tetraploids.
      In parallel to studies with sperm from diploid oysters, this study reports
      systematic factor optimization for sperm cryopreservation of tetraploid oysters.
      Specifically, this study evaluated the effects of cooling rate, single or
      combined cryoprotectants at various concentrations, equilibration time (exposure
      to cryoprotectant), and straw size. Similar to sperm from diploids, the optimal
      cooling rate was 5 degrees C/min to -30 degrees C, followed by cooling at 45
      degrees C/min to -80 degrees C before plunging into liquid nitrogen. Screening of
      single or combined cryoprotectants at various concentrations showed that a
      combination of the cryoprotectants 6% polyethylene glycol/4% propylene glycol and
      6% polyethylene glycol/4% dimethyl sulfoxide yielded consistently high post-thaw
      motility. A long equilibration (60 min) yielded higher percent fertilization, and
      confirmed that extended equilibration could be beneficial when low concentrations
      of cryoprotectant are used. There was no significant difference in post-thaw
      motility between straw sizes of 0.25 and 0.5 mL. Despite low post-thaw
      fertilization (<10%) in general for sperm from tetraploids, optimized protocols
      in the present study effectively retained post-thaw motility for sperm from
      tetraploid oysters. This study confirmed that sperm from tetraploid Pacific
      oysters were more negatively affected by cryopreservation than were those of
      diploids. One possible explanation is that sperm from these two ploidies are
      different in their plasma membrane properties (e.g., structure, permeability, and
      elasticity), and the plasma membrane of sperm from tetraploids is more sensitive
      to cryopreservation effects. The fact that combinations of non-permeating and
      permeating cryoprotectants improved post-thaw motility in sperm from tetraploids
      provided presumptive evidence for this interpretation.

PMID- 16414108
TI  - Cryopreservation of boar semen: equilibrium freezing in cryomicroscope and in
      straws.

PMID- 16414109
TI  - Effects of single and double exposure to brilliant cresyl blue on the selection
      of porcine oocytes for in vitro production of embryos.
AB  - The aim of this study was to evaluate the effectiveness and toxicity of single
      and double application of the brilliant cresyl blue (BCB) test on the selection
      of porcine oocytes as an indirect measure of oocyte growth for in vitro
      fertilization (IVF) and nuclear transfer. In the first experiment, oocytes were
      exposed to BCB before and after maturation culture and classified according to
      their cytoplasmic coloration: blue coloration and colorless. The classified
      oocytes were fertilized with spermatozoa and then cultured for 7 days. The
      percentages of maturation to metaphase II in blue oocytes at the start of
      maturation culture were higher than those of colorless oocytes (68.7-70.1% versus
      0.8-3.6%, P < 0.05). However, double application of BCB test before and after
      maturation culture had a toxic effect on fertilization and embryonic development.
      No significant differences in the blastocyst formation were found between blue
      oocytes without double application of BCB test and control oocytes without any
      application of BCB test, whereas the total cell number per blastocyst from the
      blue oocytes was higher than that from the control oocytes (48.0 versus 34.2, P <
      0.05). In the second experiment, oocytes were exposed to the BCB test before or
      after maturation culture, and then the matured oocytes were activated to evaluate
      the ability of parthenogenetic development. The proportion of blastocyst
      formation of blue oocytes classified after maturation culture was lower than that
      of blue oocytes classified before maturation culture (10.0% versus 27.0%, P <
      0.05). Therefore, double application of the BCB test before and after maturation
      culture impaired fertilization and embryonic development, whereas a single
      application before maturation culture was efficient to select oocytes for IVF and
      nuclear transfer.

PMID- 16414110
TI  - Static and fatigue compression test for particulate filler composite resin with
      fiber-reinforced composite substructure.
AB  - OBJECTIVES: The aim of this study was to determine static load-bearing capacity
      and compressive fatigue limits (CFL) of laboratory particulate filler composite
      resin (PFC) with three different types of fiber-reinforced composite (FRC)
      substructures. METHODS: A total of 420 test specimens were prepared having 1.0mm
      of FRC layer as substructure (short random, continuous unidirectional and
      bidirectional fiber orientations), and a 2.0-mm thick surface layer of PFC.
      Control specimens were prepared from plain FRC or PFC. The specimens (n=15) were
      either dry stored or water stored (37 degrees C for 2 weeks) before they were
      loaded with a steel ball (O 3.0mm) under static load until fracture and cyclic
      load with maximum controlled regimen following a staircase approach with maximum
      10(3) cycles. The decrease in CFL compared to static load was calculated and data
      were analyzed using ANOVA and Weibull statistics. RESULTS: The highest static
      loads were registered for plain FRC specimens [short random 1842 N(205),
      continuous bidirectional 2258 N(233) and unidirectional fiber orientation 538
      N(254)]. The specimens with FRC substructure and PFC coverage gave load values of
      1517 N(249), 1670 N(241) and 677 N(240), respectively. The specimens made of PFC
      only, failed with 1047 N(230) load. The CFL for 10(3) cycles ranged between 19
      and 39% of the static load values. ANOVA revealed that all factors significantly
      affected the load bearing capacity (p<0.001). SIGNIFICANCE: The results suggested
      that the material combination of continuous bidirectional or random FRC and PFC,
      gave higher CFL and static load-bearing capacity than that obtained with plain
      particulate filler composite resin.

PMID- 16414111
TI  - Fracture resistance of all-ceramic zirconia bridges with differing phase
      stabilizers and quality of sintering.
AB  - OBJECTIVES: The mechanical properties of zirconia ceramics are affected of
      stabilizing oxides and quality of sintering. The purpose of this study was to
      investigate the fracture resistance of frameworks manufactured using
      prefabricated zirconia blanks with differing stabilizing oxides and quality of
      sintering. METHODS: After dynamic loading in water, the fracture resistance was
      determined of stylized three-unit fixed partial dentures made of prefabricated
      homogenous ceramic green-body yttria-stabilized zirconia (Y-TZP) blanks (Vita YZ)
      or of densely-sintered magnesia partially stabilized zirconia (Mg-PSZ) blanks
      (Denzir-M); (i) as supplied from the manufacturer, (ii) after subjection to heat
      treatment in a way similar to veneering, and (Hi) after veneering with a feldspar
      based ceramic. RESULTS: After veneering, the load at fracture of the Vita YZ
      specimens was significantly higher (p<0.05) than that of Denzir-M. The load
      necessary to fracture Denzir-M as supplied after machining was significantly
      (p<0.05) higher than that of heat-treated Denzir-M, Vita YZ as supplied and heat
      treated Vita YZ specimens. There was no significant difference (p>0.05) between
      the heat-treated and veneered Denzir-M specimens. For Vita YZ the load at
      fracture of the veneered specimens was significantly (p<0.05) higher than of
      those as supplied or heat-treated, whereas no significant difference (p>0.05) was
      seen between heat-treated Vita YZ and Vita YZ specimens as supplied.
      SIGNIFICANCE: The fracture strength of the Vita YZ specimens increased
      considerably after veneering. Denzir-M and Vita YZ seem to be interesting
      alternatives for use as core materials in all-ceramic restorations. Long-term
      studies are, however, necessary before general clinical recommendations can be
      issued.

PMID- 16414112
TI  - Expression of HBcAg mutant with long internal deletion in Saccharomyces
      cerevisiae and observation of its self-assembly particles by atomic force
      microscopy (AFM).
AB  - An internally truncated C gene of adr hepatitis B virus core antigen with long
      internal deletion (aa81-aa116) (DeltaHBcAg with 36aa truncation) was expressed in
      Saccharomyces cerevisiae and the products (DeltarHBcAg) were purified from a
      crude lysate of the yeast by three steps: Sephrose CL-4B chromatography, sucrose
      step-gradient ultracentrifugation and CsCl-isopycnic ultracentrifugation. Results
      of ELISA test and density analysis of CsCl-isopycnic ultracentrifugation
      indicated that the purified products (DeltarHBcAg protein) with HBeAg
      antigenicity mainly located at the densities of 1.23 g ml-1. Observation and
      analysis of the purified DeltarHBcAg products by AFM indicated that the
      DeltarHBcAg (core) protein produced in S. cerevisiae could self-assemble into
      three or more size classes of core particles which exhibited a polymorphous
      distribution of DeltarHBcAg (core) particles. These different size classes of
      core particles mainly centred on the range whose mean diameter was from 10 nm to
      48 nm, especially on the position of 11 nm, 15.6 nm and the range from 27 nm to
      41 nm, respectively. Furthermore, the most number of core particles mainly
      centred on the range whose mean diameter was from 27 nm to 41 nm. These results
      above indicated that the truncated internal long fragment (aa81-aa116) probably
      had no effect on self-assembly of the HBcAg core particles which implied the
      internal length fragment (aa81-aa116) was not the sole domain for self-assembly
      of HBcAg dimer or the truncated HBcAg protein subunit formed the fresh
      interactive domain with each other. These initial results above by AFM analysis
      were very important for further research on the self-assembly, ultrastructure,
      subunit interaction and core internal deletion mutant (CIDM) function of HBcAg
      core particles.

PMID- 16414113
TI  - Thermal stabilization of collagen molecules in bone tissue.
AB  - Differential thermal calorimetry (DSC) analysis of partially dehydrated bovine
      bone, demineralized bone and bovine tendon collagen was performed up to 300
      degrees C to determine factors influencing stability of mineralized collagen in
      bone tissue. Two endothermal regions were recognized. The first, attributed to
      denaturation of collagen triple helix, was hydration dependent and had a peak at
      155-165 degrees C in bone, 118-137 degrees C in tendon and 131-136 degrees C in
      demineralized bone. The second region extended from 245 to 290 degrees C in bone
      and from 200 to 280 degrees C in tendon and was connected with melting and
      decomposition of collagen. Differences in thermodynamic parameters between
      cortical and trabecular bone tissue were stated. Activation energy of collagen
      unfolding in native bone tissue increased with dehydration of the bone. From the
      results of the present study we conclude that dehydrated bone collagen is
      thermally very stable both in native and in demineralized bone. Presence of
      mineral additionally stabilizes bone tissue.

PMID- 16414114
TI  - Behaviors of enzyme immobilization onto functional microspheres.
AB  - Micron-grade monodisperse PMMA microspheres, whose surfaces were modified with
      functional groups by co-polymerisation using functional monomer, were prepared
      via dispersion polymerisation. Characterized by their large specific surface
      area, high adsorption ability, favourable biocompatibility, these monodisperse
      micron-sized PMMA microspheres were employed as the supporting material in the
      enzyme immobilization in present work. The influential factors on the activity of
      immobilized enzyme including pH, temperature, time etc were preliminarily
      investigated. The results concluded from the experiments indicated that the
      immobilization procedure could promote the resistance of enzyme against
      temperature, pH shift and some other tough reaction conditions meanwhile prolong
      the enzymatic lifetime for storage.

PMID- 16414115
TI  - Evaluation of the anterior cruciate ligament, medial collateral ligament,
      achilles tendon and patellar tendon as cell sources for tissue-engineered
      ligament.
AB  - This study investigated four different connective tissue cell types to determine
      which cell type should be the source for seeding a tissue-engineered anterior
      cruciate ligament (ACL) replacement. Cells derived from the ACL, medial
      collateral ligament (MCL), achilles tendon (AT), and patellar tendon (PT) of New
      Zealand White rabbits were isolated and cultured. Each cell type was cultured in
      vitro after seeding on three-dimensional (3-D) braided polymer scaffolds and on
      tissue culture polystyrene that served as a control. Samples were evaluated and
      compared for their morphology, proliferation, and gene expression of fibronectin,
      type I and type III collagen. Scanning electron microscopy (SEM) photomicrographs
      verified cell attachment of all four types of connective tissue fibroblasts to
      the scaffolds. Preliminary results comparing proliferation indicate that cells
      obtained from the PT and AT have the fastest proliferation. Whereas gene
      expression of the phenotypic markers measured using real-time reverse
      transcription polymerase chain reaction (RT-PCR) indicates ACL cells have the
      highest gene expression for the matrix markers. This leads to the question of
      which cell type should be the cell source for tissue-engineering of ligament, the
      highly proliferating cells or the differentiated matrix producing cells. This
      study would suggest that ACL differentiated matrix producing cells are the most
      suitable cells for further study and development of a tissue-engineered ligament.

PMID- 16414117
TI  - Multiparametric analysis of HA14-1-induced apoptosis in follicular lymphoma
      cells.
AB  - The compounds aimed to directly bind and inhibit Bcl-2 and related anti-apoptotic
      proteins have entered the clinical or pre-clinical stage of evaluation and
      represent a promising new strategy to combat cancer. Having reported a pro
      apoptotic function of a small molecule inhibitor of Bcl-2, HA14-1, in follicular
      lymphoma cell lines, we provide herein further insights into the action of this
      compound in our model. Employing both pharmacological inhibitor studies and
      multiparametric flow cytometry assays, we demonstrated that following HA14-1
      treatment caspase activation occurs solely as a consequence of mitochondrial
      breach. Moreover, applying bivariate analysis of the DNA content and fluorochrome
      labeled inhibitor of caspases (FLICA) binding, we investigated for the first time
      the cell cycle specificity of HA14-1-evoked apoptosis in FL cells upon different
      exposure scenarios. Overall, the study provides both mechanistic and clinically
      relevant information about the action of HA14-1.

PMID- 16414116
TI  - alpha-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral
      ischemia.
AB  - The aim of the study was to investigate the effects of alpha-melanocyte
      stimulating hormone (alpha-MSH), a tridecapeptide derived from
      proopiomelanocortin (POMC), on the neurodegeneration following global cerebral
      ischemia and reperfusion in the rat. The biological activities of alpha-MSH
      include inhibition of inflammatory responses and anti-pyretic effects. Male
      Sprague-Dawley rats were subjected to four-vessel occlusion (4-VO) global
      cerebral ischemia followed by reperfusion, and treated with alpha-MSH
      (intraperitoneally, i.p.) at 30 min, and 24, 48, 72 and 96 h post-ischemia.
      Stereological quantification of the pyramidal cells in the CA1 area of the
      hippocampus showed that the number of viable neurons in ischemic rats was
      96,945+/-18,610 (means+/-SD) as compared to 183,156+/-49,935 in sham-operated
      rats (P<0.05). The number of viable neurons after treatment of ischemic rats with
      alpha-MSH was 162,829+/-34,757, i.e. significantly different from the number of
      viable neurons in ischemic rats injected with saline (P<0.01). Astrocyte
      proliferation due to the ischemic insult was markedly reduced by the treatment
      with alpha-MSH, and the loss in body weight was reduced by alpha-MSH. In
      conclusion, post-ischemic administration of alpha-MSH was found to provide
      neuroprotection in the CA1 pyramidal cell layer in the hippocampus, concomitant
      with a reduction in glial activation, indicating that alpha-MSH or mimetics
      thereof may have a potential in the treatment of stroke or other
      neurodegenerative diseases. Further studies will be required to define the post
      ischemic time window for administration of alpha-MSH.

PMID- 16414118
TI  - Enhanced cystatin C and lysosomal protease expression following 6-hydroxydopamine
      exposure.
AB  - 6-Hydroxydopamine (6-OHDA) is a selective neurotoxin used to induce apoptosis in
      catecholamine-containing neurons. Although biochemical products and reactive
      oxygen species (ROS) of 6-OHDA have been well documented, the activation of
      cellular pathways following exposure are not well understood. Apoptosis in PC12
      (Pheochromocytoma) cells was induced by 6-OHDA in a dose (10-150 microM) and time
      dependent (24-72 h) manner compared to experimental controls (no treatment). PC
      12 cells exposed to 50 microM 6-OHDA demonstrated the involvement of caspase 3
      and lysosomal protease alterations. Following 6-OHDA exposure, the caspase 3-like
      inhibitor Ac-DEVD-CHO significantly decreased 6-OHDA induced cell death. In
      addition, alterations in expression of the lysosomal cysteine and aspartic
      proteases, cathepsin B (CB) and cathepsin D (CD) and the endogenous cysteine
      protease inhibitor cystatin C were observed utilizing immunocytochemical analysis
      at 24, 48, and 72 h following 6-OHDA exposure. Furthermore, CB and CD and
      cystatin C immuno-like reactivity was more pronounced in TUNEL positive cells.
      Moreover, Western blot analysis confirmed a significant increase in protein
      expression for CB and CD at 72 h and a temporal and concentration dependent
      increase in cystatin C in response to 6-OHDA. Cells treated with pepstatin A, an
      inhibitor for CD, showed a significant decrease in cell death, however, CA-074ME,
      a specific inhibitor for CB, failed to protect cells from 6-OHDA induced cell
      death. Thus, these results suggest that apoptosis induced by 6-OHDA exposure is
      mediated in part through caspase 3 activation and lysosomal protease CD.

PMID- 16414119
TI  - Spectroscopic and substrate binding properties of heme-containing aldoxime
      dehydratases, OxdB and OxdRE.
AB  - Aldoxime dehydratase (Oxd) is a novel hemeprotein that catalyzes the dehydration
      reaction of aldoxime to produce nitrile. In this study, we studied the
      spectroscopic and substrate binding properties of two Oxds, OxdB from Bacillus
      sp. strain OxB-1 and OxdRE from Rhodococcus sp. N-771, that show different
      quaternary structures and relatively low amino acid sequence identity. Electronic
      absorption and resonance Raman spectroscopy revealed that ferric OxdRE contained
      a six-coordinate low-spin heme, while ferric OxdB contained a six-coordinate high
      spin heme. Both ferrous OxdRE and OxdB included a five-coordinate high-spin heme
      to which the substrate was bound via its nitrogen atom for the reaction to occur.
      Although the ferric Oxds were inactive for catalysis, the substrate was bound to
      the ferric heme via its oxygen atom in both OxdB and OxdRE. Electronic
      paramagnetic resonance (EPR) and rapid scanning spectroscopy revealed that the
      flexibility of the heme pocket was different between OxdB and OxdRE, which might
      affect their substrate specificity.

PMID- 16414120
TI  - AMIGO and friends: an emerging family of brain-enriched, neuronal growth
      modulating, type I transmembrane proteins with leucine-rich repeats (LRR) and
      cell adhesion molecule motifs.
AB  - Leucine-rich repeats (LRR) are protein-protein interaction domains (20-29 amino
      acid residues in length) found in proteins with diverse structure and functions.
      We note here an emerging group of central nervous system-enriched, type I surface
      proteins with an ectodomain containing LRR repeats and motifs found in cell
      adhesion molecules. Members of this group include the Amphoterin-induced gene and
      ORF-1 (AMIGO-1), LRR and Ig domain containing Nogo Receptor interacting protein I
      (LINGO-1) and the netrin-G1 ligand NGL-1. The above proteins carry, in addition
      to the LRR repeats, an immunoglobin (Ig)-like segment in their ectodomain. Two
      other related families of molecules, the NLRRs and the FLRTs, have in addition, a
      fibronectin type III repeat. The LRR domain distinguishes these molecules from
      the more extensively studied Ig-like family of cell adhesion molecules, and the
      transmembrane domain differentiate them from the family of secreted extracellular
      proteoglycans with LRRs. Functionally, many members of this group of proteins
      could modulate neurite outgrowth of neurons, at least in vitro. LINGO-1,
      initially discovered as a component of the Nogo-66 receptor complex which
      inhibits neurite growth, also regulates oligodendrocyte differentiation and
      myelination. Current knowledge and recent findings pertaining to the functions of
      this interesting group of proteins in the nervous system are discussed.

PMID- 16414121
TI  - From EEG dependency multichannel matching pursuit to sparse topographic EEG
      decomposition.
AB  - In this work, we present a multichannel EEG decomposition model based on an
      adaptive topographic time-frequency approximation technique. It is an extension
      of the Matching Pursuit algorithm and called dependency multichannel matching
      pursuit (DMMP). It takes the physiologically explainable and statistically
      observable topographic dependencies between the channels into account, namely the
      spatial smoothness of neighboring electrodes that is implied by the electric
      leadfield. DMMP decomposes a multichannel signal as a weighted sum of atoms from
      a given dictionary where the single channels are represented from exactly the
      same subset of a complete dictionary. The decomposition is illustrated on
      topographical EEG data during different physiological conditions using a complete
      Gabor dictionary. Further the extension of the single-channel time-frequency
      distribution to a multichannel time-frequency distribution is given. This can be
      used for the visualization of the decomposition structure of multichannel EEG. A
      clustering procedure applied to the topographies, the vectors of the
      corresponding contribution of an atom to the signal in each channel produced by
      DMMP, leads to an extremely sparse topographic decomposition of the EEG.

PMID- 16414122
TI  - Molecular cloning and characterization of sea bass (Dicentrarchus labrax L.)
      CD8alpha.
AB  - In this work, the gene and cDNA of the sea bass CD8alpha have been isolated and
      characterized. The coding sequence has an ORF of 666 bp. It retains the Ig motif
      that interacts with MHC and the two cysteines responsible for an intra-chain
      disulfide bridge. The hinge region contains the two essential cysteines involved
      in dimerization. The transmembrane region is well conserved in all analysed
      sequences. Similar to other teleosts, the cytoplasmic region lacks the consensus
      p56(lck) motif common in higher vertebrates. Analysis of the expression pattern
      using RT-PCR shows the highest expression in the thymus. Like in the human gene,
      the sea bass CD8alpha genomic structure is organized into six exons, which
      roughly correspond to separate functional domains of the protein. Southern
      blotting shows that CD8alpha exists as a single copy gene. Together, these
      results support the concept that the basic structure of CD8alpha has been
      maintained through evolution.

PMID- 16414123
TI  - A role for Fas-Fas ligand interactions during the late-stage neuropathological
      processes of experimental cerebral malaria.
AB  - Cerebral malaria (CM) kills more than 1 million children each year. Using a
      murine model of CM, we investigated the role of Fas-Fas ligand interactions in
      the neuropathogenesis of this disease. Lpr and Gld mice, deficient in Fas and Fas
      ligand, respectively, were protected from fatal CM, although they demonstrated
      some pathological features associated with CM in the wild type mouse. Fas-Fas
      ligand mRNA and protein expression were increased in the brain in mice with CM,
      and activated caspase-3-positive apoptotic astrocytes were observed. We suggest
      that Fas-mediated apoptosis of astrocytes is likely to be a critical factor in
      late-stage murine CM pathogenesis.

PMID- 16414124
TI  - Ropivacaine compared to bupivacaine for post-tonsillectomy pain relief in
      children: a randomized controlled study.
AB  - OBJECTIVE: To compare the effects of ropivacaine and bupivacaine on post
      tonsillectomy pain in children. METHODS: Forty-six children aged 2-12 years,
      undergoing tonsillectomy were enrolled in the study. Group 1 (n=16) received
      bupivacaine, group 2 (n=15) received ropivacaine, and a group 3 (control) (n=15)
      received 9% NaCl (saline) infiltrated around each tonsil. Pain was evaluated
      using a modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS)
      recorded 15 min and 1, 4, 12, 16, and 24h postoperatively. RESULTS: No difference
      was found in the demographic data among the groups. The pain scores were similar
      between the bupivacaine and ropivacaine groups (p>0.05). The pain scores in both
      analgesia groups were significantly (p<0.05) lower 1, 4, 12, 16, and 24h
      postoperatively compared to the control group. Analgesic requirements and the
      time to first analgesia were also significantly (p<0.05) different between the
      analgesia and control groups. CONCLUSION: Local ropivacaine infiltration is a
      safe and effective method and equivalent to bupivacaine for post-tonsillectomy
      pain.

PMID- 16414125
TI  - British Association of Paediatric Otorhinolaryngology members experience with
      recurrent respiratory papillomatosis.
AB  - OBJECTIVES: To establish current practice in the treatment of recurrent
      respiratory papillomatosis (RRP) in the UK. METHODS: Consultant members of the
      British Association of Paediatric Otorhinolaryngology (BAPO) were sent a
      questionnaire on current practice concerning the management of recurrent
      respiratory papillomatosis in the paediatric population. RESULTS: The response
      rate was 39.4% perhaps reflecting the relatively small number of
      otolaryngologists who treat this condition. Data were analysed from 41
      respondents representing 27 departments for a total of 103 patients. A total of
      13 patients (12.6%) received adjuvant medical therapies with the antiviral agent
      cidofovir accounting for 10 patients. Distal spread of RRP has occurred in 27
      (26.2%) patients. There were six reported deaths due to progressive RRP. Various
      lasers (CO(2), KTP, and pulsed dye) are the preferred method of surgical removal
      of RRP in children. Spontaneous ventilation (65.3%) is the preferred method of
      anaesthesia. Half of the consultants do not routinely send for HPV subtyping and
      75% send lesions for histological examination if there is a change in growth
      pattern. Two thirds of respondents do not routinely treat their patients with
      antireflux medication. CONCLUSION: There is a need for the establishment of a
      centralized national base to which all treating consultants can report their
      cases. The time has come for national multicenter controlled trials on the use of
      adjuvant interventions for the treatment of both severe and less severe RRP
      disease. Both of the above can be organized under the umbrella of BAPO.

PMID- 16414126
TI  - Congenital midline cervical cleft: a practical approach to Z-plasty closure.
AB  - A congenital midline cervical cleft (CMCC) is a rare developmental abnormality
      with several common features of variable severity: a midline defect of anterior
      neck skin, a superior nipple-like skin projection, and a subcutaneous fibrous
      cord. Congenital midline cervical clefts have important functional and cosmetic
      implications as cicatrical contracture with subsequent deformity may result
      without early surgical intervention. Treatment involves excision of all abnormal
      tissue, and reconstruction with Z-plasty techniques is favored because linear
      closure results in hypertrophic scarring and recurrent contracture. Z-plasty
      allows broken-line closure, reorientation of the defect in the horizontal plane
      with re-creation of a cervicomental angle, and most importantly, a lengthening of
      the anterior neck skin that aids in preventing recurrent contracture. We present
      our experience managing a congenital cervical midline cleft in a 3-month-old
      patient and describe a simple technique for planning the ideal Z-plasty closure.
      No simple description for planning the ideal closure for this defect could be
      found in the otolaryngology literature.

PMID- 16414127
TI  - Can mucosal sealing reduce tonsillectomy pain?
AB  - OBJECTIVE/HYPOTHESIS: The hypothesis tests whether sealing the tonsillectomy
      field with posterior pillar mucosa can prevent unwanted outcomes in pediatric
      tonsillectomy. STUDY DESIGN: A prospective, randomized, single blinded study was
      conducted on a sample of 39 children between 3 and 15 years of age. After
      dissection and snare tonsillectomy, the tonsillar fossa was covered on one side
      using the palatopharyngus mucosa and the other side is used as control. Pain
      scores, healing, edema and infection at the operation site were investigated.
      METHODS: The tonsillectomy sites were randomly assigned into one of two groups.
      First group contained the ones with mucosal flap sealed over the operation site
      and the second group was kept as control with the operation site left uncovered.
      All of the patients received mild analgesics. The pain assessment is done on Days
      1, 3, 5, 7 and 10 postoperatively, by using Wong-Baker faces visual analog scale.
      On the 10th postoperative day, the operation field of each side is scored
      separately for edema, healing and infection. Statistical investigation was
      performed through a software program. RESULTS: On first postoperative day, pain
      level difference was not statistically significant between the two groups
      (p>0.01). But from 3rd to 10th postoperative day, the pain level was found out to
      be lower in the mucosa sealed site (p<0.01). On the 10th postoperative day, while
      the edema was significantly more (p<0.01), healing was better (p<0.01) at the
      sutured site. Postoperative infection at operation site was not different between
      the groups (p>0.01). CONCLUSION: Covering tonsillectomy field with mucosal
      palatopharyngeal arch flap significantly reduces pain after third postoperative
      day. The flap side had better healing when compared to denuded site. But the
      sutures in the mucosal flap may cause more tissue edema. Sutures have no
      significant effect on postoperative infection. Thus, mucosal flap may be used as
      an adjuvant surgical technique to decrease tonsillectomy pain of children in
      addition to the analgesic medication.

PMID- 16414128
TI  - The bacteriostatic properties of ear tubes made of absorbable polylactic acid.
AB  - OBJECTIVE: Tympanostomy tube placement remains the most common reason children
      are brought to the operating room. Of the known complications, transient,
      recurrent, and chronic otorrhea represent the most common and challenging
      sequelae of tube insertion. This study was performed to determine if the acidic
      nature of the polymer of lactic acid (PLA), a possible material for the
      construction of ear tubes, would have bacteriostatic properties. MATERIAL AND
      METHODS: Experimental PLA tubes and control fluoroplastic tubes were inoculated
      with a broth of Pseudomonas aeruginosa or Staphylococcus aureus and incubated.
      Fluid recovered from the tubes was plated and incubated again. Colony counts were
      recorded at 24 and 48 h. Two separate trials were conducted for each organism.
      Repeated measures analysis of variance (ANOVA) models were used to assess the
      effects of the type of tube, the experimental run, and the tube by run
      interaction on colony counts. RESULTS: In the Pseudomonas experiments, the mean
      colony count of the PLA tube group (Run 1: 1.0; Run 2: 26.6) was significantly
      lower than the mean colony count in the fluoroplastic tube group (Run 1: 132.6;
      Run 2: 122.2; p=0.0150). Similarly, in the S. aureus experiments, the mean colony
      count of the PLA tube group (Run 1: 88.2; Run 2: 92.6) was significantly lower
      than the mean colony count in the fluoroplastic tube group (Run 1: 335.0; Run 2:
      325.8; p<0.0001). CONCLUSION: PLA has many properties including an apparent
      bacteriostatic quality, which may make it an attractive material for the
      construction of tympanostomy tubes.

PMID- 16414129
TI  - Factor analysis of Forced Swimming test, Sucrose Preference test and Open Field
      test on enriched, social and isolated reared rats.
AB  - Developmental and social factors are known to play a crucial role in the
      pathogenesis of affective disorders. Although it has been demonstrated that early
      life aversive experiences can be a risk factor in the development of human
      depression, most of the investigation in animals that try to model depression do
      not include postnatal manipulations. Since housing represents a fundamental
      ethological factor which modifies behavior and brain development, this study
      aimed to investigate the impact of different social and structural housing
      conditions on the development of a depressive-like syndrome in the behavioral
      despair paradigm and an anxiety-like syndrome in the unconditioned anxiety
      paradigm. The present study uses several multivariate analyses to study the
      impact of housing conditions in animal models of depression and anxiety. In this
      study, social isolation was able to reproduce the effects found in other animals
      models based on stress, suggesting that only 2 months of social isolation are
      enough to produce effects that can be useful as behavioral model of depression.
      Moreover, environmental enrichment showed an antidepressive and anxiolytic like
      effect in animal models of depression and anxiety. This effect, which has not
      been reported in earlier studies, suggests that stimulation during the first
      stages of growth might play a "protective" role on behavior and brain
      development.

PMID- 16414130
TI  - DNA macroarray and real-time PCR analysis of two nuclear photosystem I mutants
      from Chlamydomonas reinhardtii reveal downregulation of Lhcb genes but different
      regulation of Lhca genes.
AB  - In photoautotrophic organisms, the expression of nuclear genes encoding plastid
      proteins is known to be regulated at various levels. In this study, we present
      the analysis of two non-photosynthetic mutants (CC1051 and TR72) from the
      unicellular green alga Chlamydomonas reinhardtii. Both mutant strains show a
      defect in the processing of chloroplast psaA mRNA, and therefore they are assumed
      to be defective in photosystem I (PSI) assembly. We have performed macroarray
      experiments with trans-splicing mutants CC1051 and TR72 in order to analyse
      putative pleiotropic effects of nuclear-located mutations leading to a non
      functional PSI. To the best of our knowledge, this is the first example of
      Chlamydomonas cDNA macroarray analysis comparing the transcriptional regulation
      of nuclear genes in wild-type and photosystem I mutants. The macroarray results
      demonstrated a transcriptional downregulation of members of the Lhcb gene family
      more than 2-fold in both mutant strains. In addition, real-time RT-PCR
      experiments found a 4- to 16-fold reduction in transcript levels of several Lhca
      genes in TR72; whereas in CC1051, no significant change in transcript levels was
      observed. Taken together, our data suggest that a signal is transmitted from the
      chloroplast to the nucleus that serves to regulate the level of light harvesting
      polypeptides in the organelle.

PMID- 16414131
TI  - Monochloramine inhibits ultraviolet B-induced p53 activation and DNA repair
      response in human fibroblasts.
AB  - Monochloramine (NH2Cl) is one of the inflammation-derived oxidants, and has
      various effects on cell cycle, apoptosis and signal transduction. We studied the
      effects of NH2Cl on DNA repair response induced by ultraviolet B (UVB)
      irradiation in normal human diploid fibroblasts, TIG-1. TIG-1 irradiated with 20
      mJ/cm2 UVB showed marked increase in thymine dimer, which decreased by about 50%
      after 24 h. This decrease in thymine dimer was significantly attenuated (P <
      0.05) by the pretreatment of NH2Cl (200 microM), which indicated DNA repair
      inhibition. UVB induced p53 phosphorylation at Ser15, Ser20 and Ser37, and p53
      accumulation, and NH2Cl also inhibited these changes. Consequently, UVB-induced
      increase in the downstream effectors of p53, namely p21Cip1 and Gadd45a, were
      almost completely inhibited by NH2Cl. Immunoprecipitation study indicated that
      the association of p53 and MDM2, an E3 ubiquitin ligase for p53, did not change
      substantially by NH2Cl and/or UVB. The phosphorylation of p53 (Ser15 and Ser37)
      by UVB is catalyzed by ATR (ataxia telangiectasia mutated and Rad3 related
      kinase), which works as DNA damage sensor, and ATR also phosphorylates checkpoint
      kinase 1(Chk1) at Ser345. NH2Cl also inhibited the phosphorylation of Chk1
      (Ser345). As UVB-induced DNA damage is repaired by nucleotide excision repair
      (NER) in human cells, these findings indicated that NH2Cl inhibited NER through
      the inhibition of p53 phosphorylation and accumulation, and NH2Cl probably
      impaired DNA damage recognition and/or ATR activation. NH2Cl may facilitate
      carcinogenesis through the inhibition of NER that repairs DNA damages from
      various carcinogens.

PMID- 16414132
TI  - An analysis of the length of stay and effectiveness of treatment for hip fracture
      patients in Japan: evaluation of the 2002 Revision of the Medical Service Fee
      Schedule.
AB  - The length of hospital stay and effectiveness of medical treatment are analyzed
      using data of patients hospitalized due to hip fractures of four hospitals in
      Japan. The influence of the Revision of the Medical Service Fee Schedule in
      April, 2002, is evaluated, and factors which may have affected the length of stay
      and effectiveness of treatment (walking ability upon departure from the hospital)
      are also analyzed by a newly developed simultaneous equation model.

PMID- 16414133
TI  - Quantitative real-time PCR for detection and identification of Candidatus
      Liberibacter species associated with citrus huanglongbing.
AB  - Citrus huanglongbing (HLB, ex greening) is one of the most serious diseases of
      citrus. Different forms of the disease are caused by different Candidatus
      Liberobacter species, Candidatus Liberibacter asiaticus (Las), Ca. L. africanus
      (Laf) and Ca. L. americanus (Lam). The pathogen is transmitted by psyllid insects
      and by budding with contaminated plant materials. The vector psyllid Diaphorina
      citri can transmit both Las and Lam. Establishment of this vector into Florida,
      reports of Lam and Las in Brazil in 2004, and recent confirmation of HLB in
      Florida in September 2005 is of great concern to the citrus industry. Research on
      HLB has been hampered by the unculturable nature of the causal bacterium in
      artificial media. It has also been difficult to detect and identify the
      pathogens, possibly because of low concentration and uneven distribution in host
      plants and vector psyllids. In this study, we developed quantitative TaqMan PCR
      using 16S rDNA-based TaqMan primer-probe sets specific to the different Ca.
      Liberobacter spp. An additional primer-probe set based on plant cytochrome
      oxidase (COX) was used as a positive internal control to assess the quality of
      the DNA extracts. The assays do not cross-react with other pathogens or
      endophytes commonly resident in citrus plants, and are very sensitive. HLB
      pathogen DNA was successfully amplified from the equivalent of 20 ng of midrib
      tissue from symptomatic leaves. The consistent results of the assays with DNA
      extracted from plants infected by various Ca. Liberibacter species grown in
      greenhouses and in the field demonstrated a degree of reproducibility for these
      TaqMan assays. Inhibitors of the PCR that are frequently present in plant
      extracts did not affect the assay results. The population of the pathogens was
      estimated to be 5 x 10(7) and 2 x 10(6) cells/g of fresh midribs of symptomatic
      sweet orange leaves infected by Las and Lam, respectively. The ratio of pathogen
      DNA to host plant DNA was estimated by to be 1:13,000 (w/w) and 1:1000 (c/c:
      target copy/target copy) in DNA extracts obtained by a standard CTAB method. Our
      rapid, sensitive and specific TaqMan PCR assay for the detection, identification
      and quantification of Ca. Liberibacter species has been successfully used in the
      confirmation of HLB caused by Las in Florida, and will be very useful for a broad
      range of research programs as well as the regulatory response and management of
      HLB disease.

PMID- 16414134
TI  - A new MSPQC system for rapid detection of pathogens in clinical samples.
AB  - A new multi-channel series piezoelectric quartz crystal (MSPQC) system for
      detection of pathogens in clinical sample was proposed. Some factors, which
      affect the detection of pathogens by using MSPQC, were all investigated. A total
      of 650 clinical samples were detected by MSPQC and compared with licensed BACTEC
      9120 system (Becton Dickinson Diagnostic Instrument Systems, Sparks, MD, USA)
      simultaneously in the Third Xiangya Hospital of Central South University, China.
      When the incubation period was 5 days, two systems had similar detected results:
      the MSPQC system detected 123 growth of 650 (18.92%) bottles while the BACTEC
      9120 detected 125 growth of 650 (19.23%) bottles. The MSPQC had 2 false-positive
      signals and 2 false-negative signals. However, BACTEC 9120 had 3 false-positive
      signals and 0 false-negative signals. Further identifications of bacteria were
      run by VITEK-2 (bioMerieux China Ltd.), 5% sheep blood trypticase soy agar (SBA)
      and chocolate agar (CA). Comparing with BACTEC 9120, MSPQC system possesses
      following advantages: shorter average detection time, less blood volume needed,
      less false-positive results and low cost. It can also provide information in real
      time. So MSPQC has a wonderful perspective in clinical application.

PMID- 16414135
TI  - Difference in rectal dosimetry between pre-plan and post-implant analysis in
      transperineal interstitial brachytherapy for prostate cancer.
AB  - BACKGROUND AND PURPOSE: To investigate differences in rectal dosimetry between
      pre-plan ultrasonography (US) and post-implant computed tomography (CT). PATIENTS
      AND METHODS: Subjects comprised 49 patients who underwent prostate brachytherapy
      using (125)I seed implants. Prescribed dose was 145Gy to the periphery of the
      prostate. Differences in rectal dosimetry between pre-plan US and post-implant CT
      analysis were evaluated. In addition, patients were divided into two groups
      according to timing of pre-planning (pre-plan group, n=28; intraoperative pre
      plan group, n=21), and differences in rectal dosimetry between groups were
      assessed. RESULTS: The average of volume differences between pre-plan and post
      implant analysis (pre-plan minus post-implant analysis) for all patients were
      follows: -0.08 cm(3) in V60 (volume of rectal wall receiving 60% of prescribed
      dose); -0.05 cm(3) in V70; -0.16 cm(3) in V80; -0.38 cm(3) in V90; -0.40 cm(3) in
      V100; -0.32 cm(3) in V110; -0.22 cm(3) in V120; -0.15 cm(3) in V130; -0.10 cm(3)
      in V140; -0.07 cm(3) in V150; and -0.05 cm(3) in V160. Apparent differences
      between pre-plan US and post-implant CT in rectal dosimetry were small. However,
      considering the steep curve of the relationship between tolerable volume and
      dose, a large actual difference should be assumed. No advantage was identified
      for the intraoperative pre-plan group. Safe volume to avoid proctitis tended to
      be smaller on ultrasonography than on CT at 1 month. CONCLUSIONS: The present
      work shows that direct comparison of CT analysis and pre-plan US is unfavorable
      due to large differences in these modalities and overestimation of tolerable
      volume. However, by comprehending the degree of difference, comparison of data
      from CT analysis with a US pre-plan may be feasible and useful for providing
      feedback between these modalities.

PMID- 16414136
TI  - Attempts to predict the long-term decrease in lung function due to radiotherapy
      of non-small cell lung cancer.
AB  - PURPOSE: To obtain a model which can predict long-term decrease in lung function
      due to radiation damage from dose-volume data for patients with non-small cell
      lung cancer. PATIENTS AND METHODS: 27 patients were included, all long-term
      survivors after radical radiation therapy. For each patient a regression analysis
      was performed on a post-RT succession of measurements of FEV1 in order to
      estimate the decrease after 2 years and a standard error (SE) on this regression
      estimate. The modelling was based on dose-volume histograms (DVH) exported from
      the treatment planning system, and involved fits of threshold models, a mean lung
      dose model as well as more complex models based on the relative damaged volume
      (rdV). RESULTS: Decreases after 2 years of up to 28% in FEV1 was measured (median
      10%), with significant day-to-day variation in FEV1 for the individual patient.
      The threshold models predicted the long-term decrease in FEV1 well when the SE
      was interpreted as the uncertainty of the measured decrease. The best threshold
      value, marginally, was 30 Gy with an R(2) of 0.46. The mean lung dose model did
      not perform so well. A complex model based on rdV performed better than any of
      the other models (R(2)=0.52). CONCLUSION: The long-term decrease in FEV1 could be
      predicted from a simple dose-volume model when the SE was interpreted as the
      uncertainty of the measured decrease.

PMID- 16414137
TI  - Psychophysiological responses of adults who do not stutter while listening to
      stuttering.
AB  - The present study examined the psychophysiological responses of fluent listeners
      to stuttered speech. Specifically, skin conductance and heart rate changes were
      measured from adults who do not stutter while watching one-minute video speech
      samples of persons stutter read aloud. Fifteen adult participants observed three
      stuttered and three fluent speech samples, presented in random order with a two
      minute interstimulus intervals. Results revealed that observing stuttered speech
      evoked a significant increase in skin conductance and a significant deceleration
      in heart rate relative to watching fluent speech samples. These findings suggest
      that listeners are physiologically aroused by stuttering and appear to maintain
      feelings of unpleasantness to stuttered speech. Further, deceleration in heart
      rate during stuttered samples also suggest that listeners may be paying more
      attention to the stuttered speech samples as compared to the fluent speech
      samples. We speculate that aberrant and anomalous stuttering behaviors probably
      simulate the mirror neuronal mechanism eliciting the emotional arousal associated
      within them. Such physiological arousal may provide the emotional genesis to the
      listener's negative stereotypical perceptions towards people who stutter.

PMID- 16414139
TI  - Dynamics of in vivo power output and efficiency of Nasonia asynchronous flight
      muscle.
AB  - By simultaneously measuring aerodynamic performance, wing kinematics, and
      metabolic activity, we have estimated the in vivo limits of mechanical power
      production and efficiency of the asynchronous flight muscle (IFM) in three
      species of ectoparasitoid wasps genus Nasonia (N. giraulti, N. longicornis, and
      N. vitripennis). The 0.6 mg animals were flown under tethered flight conditions
      in a flight simulator that allowed modulation of power production by employing an
      open-loop visual stimulation technique. At maximum locomotor capacity, flight
      muscles of Nasonia are capable to sustain 72.2 +/- 18.3 W kg(-1) muscle
      mechanical power at a chemo-mechanical conversion efficiency of approximately 9.8
      +/- 0.9%. Within the working range of the locomotor system, profile power
      requirement for flight dominates induced power requirement suggesting that the
      cost to overcome wing drag places the primary limit on overall flight
      performance. Since inertial power is only approximately 25% of the sum of induced
      and profile power requirements, Nasonia spp. may not benefit from elastic energy
      storage during wing deceleration phases. A comparison between wing size
      polymorphic males revealed that wing size reduction is accompanied by a decrease
      in total flight muscle volume, muscle mass-specific mechanical power production,
      and total flight efficiency. In animals with small wings maximum total flight
      efficiency is below 0.5%. The aerodynamic and power estimates reported here for
      Nasonia are comparable to values reported previously for the fruit fly Drosophila
      flying under similar experimental conditions, while muscle efficiency of the tiny
      wasp is more at the lower end of values published for various other insects.

PMID- 16414138
TI  - A novel transposon for functional expression of DNA libraries.
AB  - Environmental DNA libraries are important sources for novel biocatalyst genes but
      activity screening for relevant enzymes is often inefficient. Therefore, we have
      constructed the transposon MuExpress which randomly integrates in vitro into
      existing bacterial artificial chromosome (BAC) or cosmid libraries and permits
      the inducible expression of its flanking regions in both directions. Furthermore,
      this transposon allows the bidirectional sequencing of the respective clones
      starting from unique primer binding sites.

PMID- 16414141
TI  - Using gene delivery to protect HIV-susceptible CNS cells: inhibiting HIV
      replication in microglia.
AB  - Antiretroviral chemotherapy penetrates the CNS poorly. CNS HIV, thus sheltered,
      may injure the brain and complicate control of systemic HIV infection. Microglial
      cells play a major role in HIV persistence in the CNS but are rarely targeted for
      gene delivery. Because recombinant SV40 vectors (rSV40s) transduce other
      phagocytic cells efficiently, we tested rSV40 delivery of anti-HIV genetic
      therapy to microglial cells. Microglia prepared as enriched cultures from human
      fetal brain, were transduced with marker vectors, SV(RFP) and SV(Nef/FLAG),
      respectively, carrying DsRed and HIV-1 Nef bearing a FLAG epitope. By
      immunostaining and FACS, 95% of unselected cells expressed the transgenes,
      without detectable toxicity. Microglia were transduced with SV(AT), carrying
      human alpha1-antitrypsin (alpha1AT), which blocks Env and Gag processing. SV(AT)
      treated microglia strongly resisted challenge with HIV-1BaL, even when microglia
      were transduced with SV(AT) following HIV challenge. Thus, rSV40s effectively
      transduce microglia and protect them from HIV.

PMID- 16414140
TI  - Combinatorial biosynthesis--potential and problems.
AB  - Because of their ecological functions, natural products have been optimized in
      evolution for interaction with biological systems and receptors. However, they
      have not necessarily been optimized for other desirable drug properties and thus
      can often be improved by structural modification. Using examples from the
      literature, this paper reviews the opportunities for increasing structural
      diversity among natural products by combinatorial biosynthesis, i.e., the genetic
      manipulation of biosynthetic pathways. It distinguishes between combinatorial
      biosynthesis in a narrower sense to generate libraries of modified structures,
      and metabolic engineering for the targeted formation of specific structural
      analogs. Some of the problems and limitations encountered with these approaches
      are also discussed. Work from the author's laboratory on ansamycin antibiotics is
      presented which illustrates some of the opportunities and limitations.

PMID- 16414142
TI  - Diabetic ketoacidosis complicated by axillary vein thrombosis.
AB  - A case is presented of a 39-year-old male with Down's Syndrome, who also had type
      1 diabetes of 22 years duration. He presented with diabetic ketoacidosis (DKA)
      arterial blood pH 7.17, plasma bicarbonate 13.6mmol/l, plasma glucose 26.4mmol/l
      and urine heavily positive for ketones. He recovered with standard intravenous
      fluid and insulin treatment, but on the third day of admission developed a
      swollen left arm (which had not been used for intravenous cannulation). Doppler
      ultrasound confirmed a left axillary vein thrombosis. This slowly resolved with
      anticoagulation. Review of the available literature revealed that though arterial
      thrombosis is a common complication of DKA, venous thromboembolism is
      surprisingly rare, and there appear to be no previous specific reports of
      axillary vein thrombosis complicating DKA.

PMID- 16414143
TI  - Urinary TGF-beta1 reduction related to a decrease of systolic blood pressure in
      patients with type 2 diabetes and clinical diabetic nephropathy.
AB  - With the aim to determine the influence of reducing systolic blood pressure in
      urinary TGF-beta1 of type 2 diabetes (DM2) with diabetic nephropathy (DN), 21
      subjects with type 2 diabetes and proteinuria >500 mg/24 h were studied.
      Amlodipine and ramipril were added to their previous antihypertensive treatment
      for 12 weeks. Urinary TGF-beta1 (UTGF-beta1) was determined at 0, 4, 8 and 12
      weeks. Plasma TGF-beta1 was determined at 0 and 12 weeks. Subjects whose mean
      systolic blood pressure (SBP) during treatment were under 140 mmHg were grouped
      as the better SBP controlled group (n = 11) and those with SBP equal to or
      greater than 140 mHg were grouped in a moderate SBP controlled group (n = 10).
      Compared to baseline, mean log UTGF-beta1 at 4, 8 and 12 weeks decreased (-0.22
      +/- 0.15 pg/mg; p = 0.04) in better SBP controlled group but not in the moderate
      SBP controlled group (-0.12 +/- 0.08 pg/mg, p = 0.82). Mean SBP correlated with
      UTGF-beta1 (r = 0.458, p = 0.0357), and this effect was independent of HbA1c (p =
      0.042). By controlling SBP in DM2 subjects with DN we might decrease UTGF-beta1.
      We propose that reduction of UTGF-beta1 is due to a decrease in renal TGF-beta1
      production.

PMID- 16414144
TI  - Variation of mitochondrial gene and the association with type 2 diabetes mellitus
      in a Chinese population.
AB  - Mitochondrial DNA (mtDNA) variants have been implicated in many diseases
      including diabetes mellitus. To explore whether these genetic variants contribute
      to the susceptibility for type 2 diabetes mellitus (T2DM) in a Chinese
      population, a total of 184 T2DM cases and 279 matched healthy controls were
      recruited. PCR restriction fragment length polymorphism (PCR-RFLP) analysis and
      DNA sequencing were used to determine the variants of mtDNA (including T16189C,
      G3316A, T3394C, A14693G, A3243G and C1310T). Some of them were further analyzed
      by mfold or tRNA-scan-SE software. A homoplastic A14693G, for the first time, was
      found in 4 of 184 Chinese cases, the frequency of A14693G and T3394C was 2.17%
      and 2.72%, respectively, in patients but not in the controls. Secondary structure
      prediction revealed that there were obvious conformational changes in T3394C
      mutant ND1 versus wild type and A14693G mutant tRNA(Glu) protein versus wild
      type, providing additional clues to the disease pathogenesis although A3243G and
      C1310T mutations were not detected in any patients in the two groups. The 16189
      variant among type 2 diabetes was more prevalent than in controls (36.9% versus
      28.7%, P=0.039), and stepwise multiple regression analysis showed that the 16189
      variant was an independent factor contributing to HOMA-IR (R(2)=0.043, P=0.037).
      Our results suggest that the mutations of T3394C and A14693G may contribute to
      genetic predisposition to T2DM, with the T16189C variant being associated with
      insulin resistance.

PMID- 16414145
TI  - Possibilities for intervention in adolescents' and young adults' depression from
      a public health perspective.
AB  - When considering measures to decrease the burden of disease that is caused by
      depression, depressive disorders of adolescents and young adults are of
      increasing interest. The prevalence of depressive disorders in adolescents and
      young adults is high. The probable increases in prevalence affect predominantly
      young people and their prognosis is particularly bad. This review discusses the
      potentials to influence the burden of disease through interventions such as
      therapy, including measures to detect persons at risk early, selective and
      universal prevention, and health promotion for adolescents and young adults. It
      considers the available evidence for the effectiveness of these interventions on
      the public health level. In addition, the suitability of implementation and
      ethical considerations are discussed. As a conclusion, health policy in its aim
      to reduce the burden of depressive disease should focus on increasing treatment
      rates and improving the efficiency of treatment in adolescents and young adults
      as well for depression as for other mental disease that has high co-morbidity
      with depression. In addition, the focus should be set on indicated prevention for
      children of depressed parents and--for health promotion reasons--on policies that
      impact on living-conditions of families.

PMID- 16414146
TI  - Social capital and administrative contextual determinants of lack of access to a
      regular doctor: a multilevel analysis in southern Sweden.
AB  - BACKGROUND: The aim of this study was to investigate the influence of contextual
      (social capital and administrative/neo-materialist) and individual factors on
      lack of access to a regular doctor. METHODS: The 2000 public health survey in
      Scania is a cross-sectional study. A total of 13,715 persons answered a postal
      questionnaire, which is 59% of the random sample. A multilevel logistic
      regression model, with individuals at the first level and municipalities at the
      second, was performed. The effect (intra-class correlations, cross-level
      modification and odds ratios) of individual and municipality (social capital and
      health care district) factors on lack of access to a regular doctor was analysed
      using simulation method. The Deviance Information Criterion (DIC) was used as
      information criterion for the models. RESULTS: The second level municipality
      variance in lack of access to a regular doctor is substantial even in the final
      models with all individual and contextual variables included. The model that
      results in the largest reduction in DIC is the model including age, sex and
      individual social participation (which is a network aspect of social capital),
      but the models which include administrative and social capital second level
      factors also reduced the DIC values. CONCLUSIONS: This study suggests that both
      administrative health care district and social capital may partly explain the
      individual's self reported lack of access to a regular doctor.

PMID- 16414147
TI  - The MC3 receptor binding affinity of melanocortins correlates with the nitric
      oxide production inhibition in mice brain inflammation model.
AB  - Melanocortins possess strong anti-inflammatory effects acting in the central
      nervous system via inhibition of the production of nitric oxide (NO) during brain
      inflammation. To shed more light into the role of melanocortin (MC) receptor
      subtypes involved we synthesized and evaluated some novel peptides, modified in
      the melanocyte-stimulating hormone (MSH) core structure, natural MCs and known MC
      receptor selective peptides - MS05, MS06. Since the study included both
      selective, high affinity binders and the novel peptides, it was possible to do
      the correlation analysis of binding activities and the NO induction-related anti
      inflammatory effect of the peptides. beta-MSH, gamma1-MSH, gamma2-MSH, alpha-MSH,
      MS05, Ac-MS06 and Ac-[Ser12]MS06 caused dose dependent inhibition of the
      lipopolysaccharide (LPS)-induced increase of NO overproduction in the mice
      forebrain whereas MSH core modified peptides Ac-[Asp9,Ser12]MS06, [Asp9]alpha-MSH
      and [Asp16]beta-MSH were devoid of this effect in doses up to 10 nmol per mouse.
      When the minimal effective dose required for inhibition of NO production was
      correlated with the in vitro binding activity to MC receptor subtypes a strong
      and significant correlation was found for the MC3 receptor (r = 0.90; p =
      0.0008), whereas weak correlation was present for the other receptors. Our
      results suggest that the MC3 receptor is the major player in mediating the anti
      inflammatory activity of MCs in the central nervous system.

PMID- 16414148
TI  - Modulation of peripheral inflammation by the substance P N-terminal metabolite
      substance P1-7.
AB  - The N-terminal metabolite of the undecapeptide substance P (SP), substance P1-7
      (SP1-7), is known to modulate nociception in the central nervous system (CNS) and
      often has opposite effects from SP. This study investigated the ability of SP(1
      7) to modulate the vasodilatation response to SP in anaesthetized rats under
      different injury conditions using a blister model of inflammation on the hind
      footpad. The results indicated that SP1-7 inhibited the vascular response to SP
      in a dose-dependent manner. The putative antagonists naloxone and D-Pro2-D-Phe7
      SP1-7 (D-SP1-7) reversed the effect of SP1-7. D-SP1-7 improved the responsiveness
      to SP under chronic nerve injury, which suggests a role for endogenous SP1-7 in
      this model. SP1-7 did not inhibit the response to electrical stimulation of the
      sciatic nerve, which indicates that the heptapeptide interacts at a post-terminal
      binding site. The current results suggest that SP1-7 may have inhibitory
      properties in inflammation, analogous to its antinociceptive role in the central
      nervous system.

PMID- 16414149
TI  - New ligands at the melatonin binding site MT(3).
AB  - The third melatonin binding site, MT3 is a non-classical one since it is not a
      seven transmembrane domains receptor, but an enzyme, quinone reductase 2. A major
      concern for the study of the physiological role of this site is the lack of
      specific ligands, permitting to more accurately dissect the pathways linked to
      the activation of MT3. Indeed, in the course of finding new ligands, we
      identified a new series of compounds with affinity to the binding site in the nM
      range, particularly 2,3-dimethoxy 7-hydroxy 10-methyl 5H 10H indeno(1,2-b)indol
      10-one (DMHMIO), with a Ki of 190 pM. Based on slightly different and novel
      synthons compared to most of the compounds used in melatonin pharmacology
      studies, these compounds offer new perspective for the description of the
      melatonin pathways, so much more by not having any affinity towards the MT1 and
      MT2 'classical' melatonin receptors.

PMID- 16414150
TI  - Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides
      derived from diflunisal hydrazide.
AB  - Two novel series of 4-thiazolidinone derivatives, namely 2',4'-difluoro-4
      hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl/substituted phenyl)-4
      thiazolidinone-3-yl]amides (5a-g) and 2-(2',4'-difluoro-4-hydroxybiphenyl-3
      carbonylhydrazono)-3-alkyl/aryl-4-thiazolidinones (6a-e) together with 5-(2',4'
      difluoro-4-hydroxybiphenyl-5-yl)-2-cyclohexylamino-1,3,4-oxadiazole (7a) have
      been synthesized as title compounds. 1-(2',4'-Difluoro-4-hydroxybiphenyl-3
      carbonyl)-4-alkyl/arylthiosemicarbazides (4a-g) were also obtained and used as
      intermediate to give the title compounds. All synthesized compounds were screened
      for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv,
      antiviral and antimicrobial activities against various virus, bacteria and fungi
      strains.

PMID- 16414151
TI  - Synthesis and antiinflammatory activity of 4-amino-2-aryl-5-cyano-6-{3- and 4-(N
      phthalimidophenyl)} pyrimidines.
AB  - Six new 4-amino-5-cyano-2,6-diarylpyrimidines 5a-h has been synthesized in a
      facile manner by reacting the appropriate arylamidines 4a-d with bisnitriles 3a
      e. Reduction of the nitro group of 5a-e using Pd in ethyl acetate furnished 6a-e
      in good yields. Reaction of 6a-e individually with phthalic anhydride yielded 7a
      e in good to excellent yields. The newly synthesized heterocycles were
      characterized by IR, (1)H-NMR and mass spectral data. Compounds 5f-h and 7a-e
      were also evaluated against inflammation. Pyrimidines 5g, h exhibited better
      antiinflammatory activity when compared with acetylsalicylic acid (ASA).
      Phthalimide derivatives 7a-e also presented antiinflammatory activity, and three
      of them, viz., 7a-c have been found to be twice more active than aspirin.
      Cytotoxical evaluations of compounds 7a-e using neoplastic cells (NCI-H(292) and
      Hep-2) presented 41% of growth inhibition of neoplastic cells NCI-H(292).

PMID- 16414152
TI  - An efficient approach to the asymmetric total synthesis of (-)-anisodine.
AB  - -Anisodine (l-6,7-epoxy-3-tropyl-alpha-hydroxytropate), which was isolated from
      the medicinal plant Scopolia tanguticus Maxim, was the first efficiently prepared
      using 6-beta-acetyltropine as the starting material via a key step of the
      Sharpless asymmetric dihydroxylation (AD). The intermediate compounds 10 and 11
      showed promising cholinergic activity.

PMID- 16414153
TI  - [Venous thromboembolism and cancer].
AB  - OBJECTIVES: The risk of venous thrombosis during cancer is largely increased
      especially in case of chemotherapy, surgery, advanced stage disease, coagulation
      abnormalities. Survival of patients with cancer experiencing venous thrombosis
      seems to be worse. Although thrombosis may be a presenting feature of occult
      malignancy, there are insufficient data to support a more extensive screening
      than comprehensive medical history, physical examination, routine laboratory
      tests and chest radiography. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiology of
      venous thrombosis during cancer is unspecific: venous stasis, vessel wall damage,
      hypercoagulability). Other factors like platelet abnormalities or the direct
      responsibility of chemotherapy or hormonotherapy have recently been though to
      play a causative role. Treatment of cancer-associated thrombosis usually requires
      at least 6 months of low-molecular-weight heparin therapy rather than oral
      anticoagulant. Inferior vena cava filters are not indicated. Primary prophylaxis
      of thrombosis during cancer could safely been achieved with low-molecular-weight
      heparin. Central venous catheters can be associated with thrombotic
      complications. Many risks factors have been identified: catheter's type,
      modalities of catheter's implantation, type of perfusion, bulky mediastinal
      mass... Prophylactic anticoagulation is not routinely recommended. FUTURE
      PROSPECTS AND PROJECTS: Knew oral anticoagulants could facilitate the treatment
      of venous thrombosis occurring during cancer in the next years.

PMID- 16414154
TI  - [Palmar fasciitis after carboplatin administration for an ovarian
      adenocarcinoma].

PMID- 16414155
TI  - [Giant aneurysm of the right coronary artery].
AB  - INTRODUCTION: Giant coronary aneurysms are rare and often confused with cardiac
      tumours. OBSERVATION: We report a new case of this type of aneurysm occurring on
      the right coronary artery revealed by a cardiac congestion. COMMENTS: These
      aneurysms can be due to inflammatory diseases or dysplasia. But in these
      pseudotumoral forms, atherosclerosis is the main aetiology. The diagnosis and
      treatment require surgery and histological examination.

PMID- 16414156
TI  - The development and evaluation of the use of a virtual learning environment
      (Blackboard 5) to support the learning of pre-qualifying nursing students
      undertaking a human anatomy and physiology module.
AB  - Students commence nurse education with varying levels of understanding of human
      anatomy and physiology due to a wide range of previous exposure to the topic. All
      students, however, are required to attain a broad knowledge of this topic prior
      to qualification. This paper describes the use of a Virtual Learning Environment
      (VLE), Blackboard 5, and the associated development of appropriate resources
      aimed at supporting nursing students undertaking a human anatomy and physiology
      module at Higher Education Level 1. The VLE was used as part of a blended
      learning approach. The results suggested that the majority of students utilised
      the VLE throughout the academic year. Opportunities for independent and self
      directed learning were available in that students chose when and where to learn.
      Students generally commented favourably on ease of use and type of resources
      available. Frequency of use of the VLE, however, did not correlate strongly with
      the final examination mark achieved. Overall the VLE and the associated available
      resources appeared useful in supporting student learning and has been adopted for
      use in subsequent years.

PMID- 16414157
TI  - Efficiency of HPV 16 L1/E7 DNA immunization: influence of cellular localization
      and capsid assembly.
AB  - Infections by human papillomaviruses (HPV) are the major cause of uterine cancer
      in women worldwide. Aiming to develop a combined prophylactic and therapeutic
      vaccine we have previously demonstrated immunogenicity of chimeric virus-like
      particles consisting of a C-terminally truncated HPV 16 L1 capsid protein fused
      to an E7 portion. Here we show that genetic vaccination with a corresponding DNA
      was inefficient in the induction of a L1-specific prophylactic immune response.
      DNA immunization with C-terminally truncated HPV 16 L1 genes of different lengths
      revealed that only short deletions (L1(1-498)) were tolerated for eliciting a
      humoral immune response against viral capsids. This correlates with the
      observation that the C-terminal sequences are critical for nuclear localization,
      capsomere and capsid assembly. However, only the ability of L1 protein to form
      capsomeres or capsids showed a direct influence on the outcome of the immune
      response. C-terminal insertion of 60 amino acids of E7 was tolerated in fusion
      constructs, whereas insertion of full-length E7(1-98) or shuffled E7 (149 aa)
      completely abolished the humoral immune response. The L1(1-498)/E7(1-60) fusion
      construct not only induced L1-specific antibodies but also L1- and E7-specific
      CTL responses after DNA vaccination.

PMID- 16414158
TI  - Enhanced immunogenicity of microencapsulated multiepitope DNA vaccine encoding T
      and B cell epitopes of foot-and-mouth disease virus in mice.
AB  - The role of poly(D,L-lactic-co-glycolic acid, PLGA) microparticles on enhancing
      immune responses of multiepitope DNA vaccines was investigated in vitro and in
      vivo. pcDNA-SG encoding T and B cell epitopes of foot-and-mouth disease virus
      (FMDV) was encapsulated into PLGA microparticles. PLGA microparticles could
      protect themselves from nuclease degradation in vitro. PLGA-pcDNA-SG
      microparticles could be uptaken by cells and expressed His-tagged SG immunogen in
      vitro and in vivo. A prolonged expression and presentation of SG immunogen were
      observed by confocal laser scanning microscopy in the lymphocytes from the mice
      incubated with PLGA-pcDNA-SG microparticles, compared with the mice immunized
      with naked pcDNA-SG. PLGA-pcDNA-SG microparticles displayed a significant
      stronger immunogenicity than naked DNA vaccines with a higher titer of virus
      specific antibody, elevated IFN-gamma production and enhanced lymphocyte
      proliferation. PLGA-DNA microparticle could elicit augmented humoral and cellular
      responses with reduced amounts and times of immunization.

PMID- 16414159
TI  - The PPD-specific T-cell clonal response in UK and Malawian subjects following BCG
      vaccination: a new repertoire evolves over 12 months.
AB  - Mycobacterium bovis bacille Calmette Guerin vaccination protects against
      pulmonary tuberculosis in the United Kingdom but not in Malawi. We investigated
      whether a difference in the clonal T-cell response to BCG vaccination might
      account for this. The results of clonal analysis were compared to those obtained
      by skin testing and in a whole blood interferon gamma assay. Pre-vaccination
      antigen specific T-cell clones were detected, but the majority of clones present
      12 months after vaccination were not present earlier. The magnitude of the clonal
      response did not correlate well with results of the other assays. These data
      indicate that single assays may not be reliable and that a stable memory T-cell
      repertoire is slow to develop.

PMID- 16414160
TI  - Influenza vaccination coverage in adults belonging to defined target groups,
      Germany, 2003/2004.
AB  - In 2003, a nationwide cross-sectional study was conducted to assess the current
      influenza vaccination coverage of the adult population of Germany, especially in
      persons belonging to defined target groups. Of 666 surveyed persons, 190
      (adjusted 24%) had received influenza vaccination and 419 participants belonged
      to at least one target group. Of those, 28% (95% confidence interval (CI) 22-35%)
      in former West Germany and 45% (95% CI 38-52%) in former East Germany had
      received influenza vaccination. The offer for vaccination by a physician was
      associated with a high likelihood for vaccination (odds ratio (OR) 19.0; 95% CI
      8.9-40.6). Another important factor influencing vaccination uptake was having
      received influenza vaccination in prior seasons (OR 7.1; 95% CI 3.8-13.2).
      Vaccination coverage in the adult population of Germany remains unsatisfactory.
      Physicians have an important role and should be targeted for campaigns to offer
      the vaccination more frequently in particular to persons belonging to target
      groups.

PMID- 16414161
TI  - Taiwan's industrial heavy metal pollution threatens terrestrial biota.
AB  - The bioconcentration levels of essential (Cu, Fe, Mg, Mn, and Zn) and non
      essential (As, Cd, Hg, Pb, and Sn) elements have been investigated in different
      terrestrial biota such as fungi, plant, earthworm, snail, crab, insect,
      amphibian, lizard, snake, and bat including the associated soil, to investigate
      the ecosystem health status in Kenting National Park, Taiwan. High
      bioconcentrations of Cd, Hg, and Sn in snail, earthworm, crab, lizard, snake, and
      bat indicated a contaminated terrestrial ecosystem. High concentrations of Cd,
      Hg, and Sn in plant species, effective bioaccumulation of Cd by earthworm, snail,
      crab and bat, as well as very high levels of Hg found in invertebrates,
      amphibians, and reptiles revealed a strong influence from industrial pollution on
      the biotic community. This study for the first time presents data on the impact
      of heavy metal pollution on various terrestrial organisms in Taiwan.

PMID- 16414163
TI  - Men's constructions of smoking in the context of women's tobacco reduction during
      pregnancy and postpartum.
AB  - Men's smoking is largely under-examined despite research that has consistently
      linked partner smoking to pregnant women's smoking and smoking relapse in the
      postpartum. An on-going qualitative study involving 31 couples in Canada
      exploring the influence of couple interactions on women's tobacco reduction
      provided the opportunity to examine men's smoking in the context of women's
      tobacco reduction or cessation during pregnancy and postpartum. Individual open
      ended interviews with 20 men who smoked were conducted at 0-6 weeks following the
      birth of their infants and again at 16-24 weeks postpartum. Constant comparative
      methods were used along with social constructivist perspectives of fatherhood and
      gender to guide data analysis and enhance theoretical sensitivity. Four themes
      emerged in men's accounts of their tobacco use: (1) expressing masculinity
      through smoking, (2) reconciling smoking as a family man, (3) losing the freedom
      to smoke, and (4) resisting a smoke-less life. Men's reliance on and commitment
      to dominant ideals of masculinity seemed to preclude them from viewing their
      partner's tobacco reduction or cessation for pregnancy as an opportunity for
      cessation. Expectant and new fathers who smoke, however, may be optimally
      targeted for cessation interventions because it is a time when men experience
      discomfort with their smoking and when discontinuities in everyday life
      associated with the transition to fatherhood and presence of a new baby provide
      opportunities for establishing new routines. Implications for gender-sensitive
      smoking cessation interventions are discussed.

PMID- 16414162
TI  - Changes in family financial circumstances and the physical health of married and
      recently divorced mothers.
AB  - This study investigates how divorce followed by single parenthood undermines the
      long-term physical health of rural mothers using four waves of survey data
      collected in Iowa, USA from 336 married and 80 divorced mothers during a 10-year
      period. Findings generally support the hypothesized pathways in that single
      parenthood creates financial difficulties for rural mothers. Furthermore, this
      financial adversity is linked to self-assessed physical health trajectories that
      then contribute to change in morbidity. This reflects the developmental course of
      morbidity during the middle years. Methodologically, this extends existing
      research on the association between women's marital status and well being by
      explicitly examining individual trajectories of change in family financial strain
      and physical health, as well as by examining the dynamic association between both
      during the middle years.

PMID- 16414164
TI  - Variations in provider conceptions of integrative medicine.
AB  - Consumers often turn to complementary and alternative medicine (CAM) and use it
      concurrently with conventional medicine to treat illnesses and promote wellness.
      However, prior studies demonstrate that these two paradigms are often not
      combined effectively. Consumers often do not tell physicians about CAM treatments
      or CAM practitioners about conventional treatments that they are using. This can
      lead to inefficient care and/or adverse interactions. There is also a lack of
      consensus about the structure and practice of integrative medicine among the
      various types of practitioners. This qualitative study aimed to identify key
      domains and develop a conceptual model of integrative medicine at the provider
      level, using a grounded theory approach. Purposive sampling was used to select 50
      practitioners, including acupuncturists, chiropractors, internists/family
      practitioners, and physician acupuncturists in private practice and at academic
      medical centers in Los Angeles. We conducted semi-structured, in-depth interviews
      with practitioners and then identified core statements that describe
      practitioners' attitudes and behaviors toward integrative medicine. Core
      statements were free pile sorted to ascertain key domains of integrative
      medicine. Four key domains of integrative medicine were identified at the
      provider level: attitudes, knowledge, referral, and practice. Provider age,
      training, and practice setting also emerged as important factors in determining
      clinicians' "orientation" toward integrative medicine. "Dual-trained"
      practitioners, such as physician acupuncturists, exemplified clinicians with a
      greater orientation toward integrative medicine. They advocated an open-minded
      perspective about other healing traditions, promoting co-management with and
      making referrals to practitioners of other paradigms, and treating patients with
      both CAM and conventional healing modalities.

PMID- 16414165
TI  - Of spineless babies and folic acid: evidence and efficacy in biomedicine and
      ayurvedic medicine.
AB  - The basic premise of the paper is that Western medicine's co-opting of specific
      technologies and materials from other (indigenous) medical traditions, stripped
      of the original theories underlying their use, has problematic consequences for
      the practitioners and patients of both source and recipient traditions. The paper
      begins by illustrating the historical continuity of this process by way of an
      example from India's colonial era. The fact that specific practices or materials
      are regarded as biomedically useful because they 'work' (are efficacious) does
      not mean that the 'traditional' theories underlying them are seen as correct. The
      knowledge contained in these traditions is not counted as legitimate, as the
      emphasis in biomedicine (the legitimate canon) on an identifiable concrete
      location in the body for the source of health problems creates difficulties-both
      for patients when their problems are not provided with a cause that matches their
      subjective awareness, and for the practitioners of other traditions whose
      patients have been exposed to biomedicine. The paper goes on to demonstrate,
      using case examples from extended ethnographic fieldwork in southern India, how
      this is played out in a setting in which an educated Indian patient population
      accepts this form of knowledge as legitimate but espouses ayurvedic therapy.
      Notions of 'evidence' are shown to be central to the interplay between biomedical
      and other medical traditions, since objective tests and measures in biomedicine
      are accepted as the only legitimate 'evidence' of cure, but these do not
      necessarily accord either with the premises of these other traditions or with
      patients' subjective perceptions of well-being. Returning to an acceptance and
      practice of other traditions, consequently, requires nothing less than a
      fundamental cognitive shift in the grounds for what constitutes 'evidence.'

PMID- 16414167
TI  - Adult life behavioral consequences of early maternal separation are alleviated by
      escitalopram treatment in a rat model of depression.
AB  - In order to study the gene-environment interaction as well as investigate
      prophylactic/ameliorative effects of early intervention on development of adult
      life psychopathology, we superimposed maternal separation on an animal model of
      depression the Flinders Sensitive Line (FSL) rats and their controls the Flinders
      Resistant Line (FRL) rats and studied behavior following treatment with
      escitalopram. Animals were maternally separated for 180 min/day from postnatal
      day 2 (PND 2) to 14. The control groups were left undisturbed. Treatment with
      escitalopram or vehicle admixed to food pellets was commenced on PND 43 and
      continued until PND 73. The Porsolt swim test was carried out on PND 65. Baseline
      FRL/FSL differences in body weight and swim duration, considered to be an inverse
      index of depression, were found (p's<0.001). In the FSL, maternal separation
      further decreased swim duration (p<0.001) while the FRL strain was unaffected.
      Escitalopram had no effect in FRL, but increased swim duration in both maternally
      non-separated and separated FSL (p<0.05 and p=0.001; respectively). These results
      confirm the strain differences between the FSL and FRL and demonstrate that the
      long-term effects of early life adverse experience will to a significant degree
      depend on the genetic make-up of an individual. Finally, antidepressant treatment
      reversed behavioral abnormalities caused by genetic and environmental factors.
      This study highlights the importance of genetic factors in susceptibility to
      early life adverse events, and demonstrates the efficiency of early
      antidepressant treatment in reversing behavioral abnormalities, both those caused
      by genetic factors and by environmental factors.

PMID- 16414166
TI  - Differential effects of classical neuroleptics and a newer generation
      antipsychotics on the MK-801 induced behavioural primitivization in mouse.
AB  - Cognitive dysfunction plays an important role in mental disorders like
      schizophrenia and may involve inadequate glutamatergic signalling in different
      regions of the brain, mediated by e.g. glutamatergic N-methyl-D-aspartate (NMDA)
      receptors. In rodents, NMDA receptor antagonists often increase motor activity;
      in addition they induce a more primitive and undifferentiated behavioural
      pattern, which we believe may correspond to some of the cognitive defects seen in
      schizophrenia. In the present study, the movement pattern of mice treated with
      the uncompetitive NMDA receptor antagonist MK-801 in conjunction with six
      antipsychotic agents, some with reported clinical effects on cognition, was
      characterised and quantified. The classical neuroleptic drugs chlorpromazine and
      trifluoperazine, the atypical antipsychotic agents ziprasidone and olanzapine,
      the gamma-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor
      potentiator CX516 and the serotonin (5-HT)2A-antagonist M100907 were tested. In
      accordance with previous observations, MK-801 was found to induce a primitive and
      monotonous behavioural pattern dominated by forward locomotion; spatial
      movements, the number of switches between the states moving and stationary, and
      rearing frequency were reduced. All test substances counteracted MK-801-induced
      hyperactivity, but differed in their ability to improve behavioural quality.
      Chlorpromazine and trifluoperazine were unable to restore behavioural diversity
      while ziprasidone, olanzapine, CX516 and M100907 restored it to varying degrees.
      A striking similarity in movement pattern was seen between the hypoglutamatergic
      mice treated with the AMPA-receptor agonist CX516, and those receiving the 5HT2A
      antagonist M100907.

PMID- 16414168
TI  - Plasma levels of homovanillic acid, 5-hydroxyindoleacetic acid and cortisol, and
      serotonin turnover in depressed patients.
AB  - Plasma levels of ACTH, cortisol and monoamines were examined in 23 depressed
      patients and 31 healthy subjects. Patients showed increased plasma cortisol
      levels, but not plasma adrenocorticotropic hormone (ACTH) levels. The plasma
      levels of a dopamine metabolite, homovanillic acid (HVA) and 3,4
      dihydroxyphenylacetic acid (DOPAC), were significantly decreased in the patients.
      In contrast, the plasma levels of a serotonin (5-HT) metabolite,
      hydroxyindoleacetic acid (5-HIAA), and 5-HT turnover (5-HIAA/5-HT) were increased
      in the depressed patients. Therefore, plasma levels of HVA and 5-HIAA are proven
      to be dissociable. Furthermore, plasma levels of 5-HIAA and L-DOPA have positive
      relationships with severity of depression. On the basis of this and the previous
      studies, we speculate that an increase in the plasma 5-HIAA levels might be a
      compensatory mechanism for stress, whereas 5-HT turnover might reflect depressive
      state. Taken together, plasma levels of HVA and 5-HIAA, and 5-HT turnover (5
      HIAA/5-HT) could be good markers for evaluating depression.

PMID- 16414170
TI  - Quantitative structure activity relationship for the computational prediction of
      nitrocompounds carcinogenicity.
AB  - Several nitrocompounds have been screened for carcinogenicity in rodents, but
      this is a lengthy and expensive process, taking two years and typically costing
      2.5 million dollars, and uses large numbers of animals. There is, therefore, much
      impetus to develop suitable alternative methods. One possible way of predicting
      carcinogenicity is to use quantitative structure-activity relationships (QSARs).
      QSARs have been widely utilized for toxicity testing, thereby contributing to a
      reduction in the need for experimental animals. This paper describes the results
      of applying a TOPological substructural molecular design (TOPS-MODE) approach for
      predicting the rodent carcinogenicity of nitrocompounds. The model described
      79.10% of the experimental variance, with a standard deviation of 0.424. The
      predictive power of the model was validated by leave-one-out validation, with a
      determination coefficient of 0.666. In addition, this approach enabled the
      contribution of different fragments to carcinogenic potency to be assessed,
      thereby making the relationships between structure and carcinogenicity to be
      transparent. It was found that the carcinogenic activity of the chemicals
      analysed was increased by the presence of a primary amine group bonded to the
      aromatic ring, a manner that was proportional to the ring aromaticity. The nitro
      group bonded to an aromatic carbon atom is a more important determinant of
      carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the
      TOPS-MODE approach was compared with four other predictive models, but none of
      these could explain more than 66% of the variance in the carcinogenic potency
      with the same number of variables.

PMID- 16414169
TI  - Obsessive compulsive symptoms associated with quetiapine treatment in a
      schizophrenic patient: a case report.
AB  - PURPOSE: Atypical antipsychotics (AAPs) are used as adjunct therapy in the
      treatment of resistant obsessive-compulsive symptoms (OCSs). Paradoxically other
      reports suggest that AAPs, particularly clozapine, risperidone, and olanzapine
      can induce de novo emergence or exacerbation of OCSs in psychotic patients. The
      authors present here the first report suggesting an association between de novo
      appearance of OCSs and quetiapine treatment in a schizophrenic patient. CASE: The
      patient was a 33-year-old woman with the diagnosis of paranoid schizophrenia, who
      displayed OCSs for the first time during treatment with quetiapine. The symptoms
      reduced remarkably when fluoxetine was added to her treatment regimen while
      keeping the quetiapine dosage unchanged. CONCLUSION: AAP-induced OCSs merit
      consideration and early identification, as these drugs are now widely in use in
      clinical practice. This rare but disabling side effect should also be monitored
      in quetiapine treated schizophrenic patients.

PMID- 16414171
TI  - Gene expression and estrogen sensitivity in rat uterus after developmental
      exposure to the polybrominated diphenylether PBDE 99 and PCB.
AB  - Considering the presence of polybrominated diphenylethers (PBDEs) in human milk
      and cord blood, and the estrogenic activity of some congeners, it is conceivable
      that PBDEs may interact with developing neuroendocrine systems. We investigated
      effects of 2,2',4,4',5-pentabromo-DE (PBDE 99), a major congener in human milk,
      on development of brain and reproductive organs, with focus on estrogen target
      gene expression. Time-pregnant Long Evans rats were subcutaneously injected with
      PBDE 99 (1 or 10 mg/kg/day), the PCB mixture Aroclor 1254 (10 mg/kg/day), known
      to interfere with sexual development, or vehicle, from gestational day (GD) 10 to
      GD 18. In female offspring, anogenital distance was unaffected by PBDE 99 but
      increased by Aroclor; puberty (vaginal opening) was not significantly changed.
      Adult PBDE 99-exposed offspring exhibited unchanged uterine weight but increased
      ovarian weight. Uterine mRNA levels of estrogen target genes were determined by
      real-time PCR. Progesterone receptor (PR) mRNA was down-regulated at both PBDE 99
      doses, estrogen receptor alpha (ER alpha), ER beta and insulin-like growth factor
      I (IGF-I) were up-regulated at the lower dose. Aroclor induced different effect
      patterns. In order to investigate possible changes in sensitivity of target genes
      to estrogen, some offspring were ovariectomized at 10 weeks of age, s.c. injected
      with estradiol-17beta (E2, 10 microg/kg) or vehicle at 12 weeks, and sacrificed 6
      h later. PBDE 99 dose-dependently reduced the magnitude of IGF-I mRNA induction
      by E2, and increased the magnitude of ER beta repression. PBDE 99 also influenced
      baseline levels of PR, IGF-I and ER beta mRNAs in ovariectomized, vehicle
      injected controls. These data indicate that developmental exposure to PBDE 99 at
      doses devoid of general toxicity, affects the regulation of estrogen target genes
      in uterus. Since PBDE 99 was detected in blood and adipose tissue of adult
      offspring, these effects may result from interactions with developmental
      processes, adult functions, or a combination of both.

PMID- 16414172
TI  - Incidence and factors associated with endodontic inter-appointment emergency in a
      dental teaching hospital in China.
AB  - OBJECTIVE: To assess the incidence of endodontic inter-appointment emergency
      (EIE) in a dental teaching hospital in China, and to correlate its occurrence
      with preoperative and treatment parameters. METHODS: Three thousand six hundred
      and ninety six cases were collected at root canal treatment appointments on
      demographics, presenting symptoms, treatment procedures and periradicular status.
      The operators consisted of faculty, undergraduate students and advanced trainees.
      Root canals were conventionally instrumented and then medicated. No systemic
      medication was prescribed. In cases EIE developed between appointments, an
      emergency visit was arranged and active treatment was carried out. The data of
      EIE cases were statistically analyzed using the chi-square test and a multiple
      logistic regression model. RESULTS: The overall incidence of EIE was 5%, which
      rate was 5.5% in females and 4.3% in males. Analyses of the potential factors
      revealed that patient age, tooth location, preoperative percussion pain and pulp
      status were the most important independent variables. CONCLUSION: EIE was
      significantly associated with some host factors (patient age, tooth location) and
      presenting factors (preoperative percussion pain, pulp status).

PMID- 16414173
TI  - Developmental origin and fate of meso-diencephalic dopamine neurons.
AB  - Specific vulnerability of substantia nigra compacta neurons as compared to
      ventral tegmental area neurons, as emphasized in Parkinson's disease, has been
      studied for many years and is still not well understood. The molecular codes and
      mechanisms that drive development of these structures have recently been studied
      through the use of elegant genetic ablation experiments. The data suggested that
      specific genes at specific anatomical positions in the ventricular zone are
      crucial to drive development of young neurons into the direction of the
      dopaminergic phenotype. In addition, it has become clear the these dopaminergic
      neurons are present in the diencephalon and in the mesencephalon and that they
      may contain a specific molecular signature that defines specific subsets in terms
      of position and function. The data indicate that these specific subsets may
      explain the specific response of these neurons to toxins and genetic ablation.

PMID- 16414174
TI  - Association of behavioral inhibition with hair pigmentation in a European sample.
AB  - Behavioral inhibition, a temperamental trait signalling a predisposition to
      childhood and adolescent anxiety disorders, is slightly more frequent in America
      among Caucasian children having blue irises. This paper examines a community
      sample of 101 German toddlers assessed for behavioral inhibition in a
      standardized laboratory procedure. Hair pigmentation was found to be
      significantly associated with behavioral inhibition in the sense that blond
      children exhibited higher fear scores. As in American samples, blue-eyed children
      had a higher fear score than did other children, but this difference was not
      statistically significant.

PMID- 16414175
TI  - Caesarean section rates in pregnancies complicated by gastroschisis in a tertiary
      referral centre over a 5-year period (1997-2002).

PMID- 16414178
TI  - Structure and function of human 17beta-hydroxysteroid dehydrogenases.
AB  - 17Beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the NAD(P)(H)
      dependent oxidoreduction at C17 oxo/beta-hydroxyl groups of androgen and estrogen
      hormones. This reversible reaction constitutes an important pre-receptor control
      mechanism for nuclear receptor ligands, since the conversion "switches" between
      the 17beta-OH receptor ligands and their inactive 17-oxo metabolites. At present,
      14 mammalian 17beta-HSDs are described, of which at least 11 exist within the
      human genome, encoded by different genes. The enzymes differ in their expression
      pattern, nucleotide cofactor preference, steroid substrate specificity and
      subcellular localization, and thus constitute a complex system ensuring cell
      specific adaptation and regulation of sex steroid hormone levels. Broad and
      overlapping substrate specificities with enzymes involved in lipid metabolism
      suggest interactions of several 17beta-HSDs with other metabolic pathways.
      Several 17beta-HSDs enzymes constitute promising drug targets, of particular
      importance in cancer, metabolic diseases, neurodegeneration and possibly
      immunity.

PMID- 16414177
TI  - HESX1 expression in human normal pituitaries and pituitary adenomas.
AB  - Hesx1 is a paired-like homeobox gene first expressed during mouse embryogenesis
      in the anterior midline visceral endoderm. As gastrulation proceeds, Hesx1 is
      expressed in the ventral prosencephalon and, subsequently, at E9.0 appears in the
      ventral diencephalon and in the thickened layer of oral ectoderm that give rise
      to Rathke's pouch, the primordium of the anterior pituitary gland. Hesx1
      continues to be expressed in the developing anterior pituitary until E11.5 when
      its transcripts disappear in a spatiotemporal sequence corresponding to
      progressive pituitary cell differentiation, becoming undetectable by E15.5. In
      the present study, we investigated whether HESX1 is expressed during adult life
      in human normal pituitaries and in different types of human pituitary adenomas.
      We analysed, using quantitative RT-PCR method, three normal pituitaries, seven GH
      , two TSH-, two PRL-, one ACTH-secreting adenomas, and seven nonfunctioning
      pituitary tumors. HESX1 mRNA was found to be expressed in normal pituitaries and
      in all the pituitary tumors that we have analysed. These results suggest that in
      humans HESX1 is not turned-off during the adult life as it occurs in mice. Thus,
      HESX1 in humans might play a role in the maintenance of the anterior pituitary
      cell types and function, as well as in the differentiation of pituitary adenomas,
      whose pathogenetic mechanisms remain to be further investigated. This is the
      first study on HESX1 expression in humans during adult life.

PMID- 16414179
TI  - Epididymis-specific promoter-driven gene targeting: a transcription factor which
      regulates epididymis-specific gene expression.
AB  - Mammalian spermatozoa undergo several modification and finally acquire the
      ability to fertilize during epididymal transit. One of the distinct features of
      the epididymis is that it displays a highly regionalized pattern of gene
      expression. This tissue-, region-, and cell-specific pattern of gene expression
      is critical for the maintenance of a fully functional epididymis. One would
      hypothesize that disrupting this process provides an ideal approach to male
      contraception, since it would not interfere with testicular endocrine output or
      sperm production. To achieve this purpose, we studied a cluster of epididymis
      specific lipocalin genes for understanding the specific mechanisms involved in
      the control of gene expression in the epididymis. We have identified six
      epididymis-specific lipocalin genes that are differently regulated and
      regionalized in the epididymis. Lipocalin 5 [Lcn5 or epididymal retinoic acid
      binding protein (E-RABP)] is a member of this epididymis-specific lipocalin gene
      cluster, which binds hydrophobic molecules such as retinoic acid. We have
      previously shown that the 5kb promoter fragment of the Lcn5 gene confers both
      androgen-dependent regulation and epididymis-specific gene expression in
      transgenic mice whereas 0.6 kb promoter fragment does not. To further narrow down
      the important cis-regulatory elements that regulate gene expression in the
      epididymis, we studied the Lcn5 promoter in both transgenic mice and immortalized
      epididymal cells. We have found that 1.8kb promoter fragment of the Lcn5 gene was
      sufficient for tissue- and region-specific expression in transgenic mice, and
      that a transcription factor Forkhead box A2 (Foxa2) interacts with the androgen
      receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 and
      1.3 kb. Our finding provides a framework for further analysis of the epididymal
      lipocalin gene regulation and modulated control of epididymis-specific
      expression.

PMID- 16414180
TI  - The regulation and inhibition of 17beta-hydroxysteroid dehydrogenase in breast
      cancer.
AB  - 17Beta-hydroxysteroid dehydrogenase Type 1 (17beta-HSD1) has a pivotal role in
      regulating the synthesis of oestradiol (E2) within breast tumours. In whole body
      studies in postmenopausal women with breast cancer the conversion of oestrone
      (E1) to E2 (4.4+/-1.1%) was much lower than the inactivation of E2 to E1 (17.3+/
      5.0%). In contrast, an examination of in vivo oestrogen metabolism within breast
      tumours revealed that whereas little metabolism of E2 occurred, E1 was converted
      to E2 to a much greater extent in malignant (48+/-14%) than in normal (19+/-6%)
      breast tissue. Findings from these studies originally suggested that oestrogen
      metabolism within breast tumours may differ from the mainly oxidative direction
      found in most other body tissues and that the activity of 17beta-HSD1 might be
      regulated by tumour-derived factors. Several growth factors (e.g. IGF-I, IGF-II)
      and cytokines (e.g. IL-6, TNFalpha) have now been identified which can markedly
      stimulate the activity of 17beta-HSD1 and such a mechanism may account for the
      high concentrations of E2 found in most breast tumours. Cells of the immune
      system, which can infiltrate breast tumours, are thought to be a major source of
      the growth factors and cytokines which can modulate 17beta-HSD1 activity. Given
      the central role that 17beta-HSD1 has in regulating breast tumour E2
      concentrations the development of potent inhibitors of this enzyme has recently
      attracted considerable attention. Our initial studies in this area explored the
      use of derivatives of E1 as inhibitors, with 2-ethyl- and 2-methoxy E1 being
      found to inhibit 17beta-HSD1 activity in T-47D breast cancer cells by 96+/-2 and
      91+/-1% respectively at 10 microM, but with a lack of specificity. Using the E1
      scaffold a number of potent, selective 17beta-HSD1 inhibitors have now been
      identified including E1- and 2-ethyl-E1 containing a side chain with a m
      pyridylmethylamidomethyl functionality extending from the 16beta position of the
      steroid nucleus. At 10 microM these compounds both inhibited 17beta-HSD1 activity
      by >90%, however some inhibition of 17beta-HSD2 activity was exhibited by the E1
      derivative (25%) but not the 2-ethyl analogue. It is now apparent that 17beta
      HSD1 activity contributes to the high E2 concentrations found in most breast
      tumours. The identification of potent, selective novel 17beta-HSD1 inhibitors
      will allow their efficacy to be tested in in vitro and in vivo studies.

PMID- 16414181
TI  - Epididymal secreted protein Crisp-1 and sperm function.
AB  - Crisp-1 is a member of the cysteine-rich secretory protein family. This family of
      proteins is characterized by the presence of 16 conserved cysteine residues, the
      characteristic from which the family name is derived. Members of the Crisp
      protein family are found in the secretions of the reproductive tract and salivary
      glands, including venom toxins from several species of snakes and lizards. The
      Crisp proteins are modular, each containing an amino terminal pathogenesis
      related (PR)-like domain and a carboxyl terminal cysteine-rich domain (CRD)
      connected by a hinge region. Sequence and structural similarities to proteins
      with known functions suggest that the Crisp family of proteins may act by
      regulating cellular ion channels. Rat Crisp-1 is synthesized as two distinct
      isoforms (referred to as Proteins D and E) by the epididymal epithelium and both
      are secreted into the luminal fluid where they interact with spermatozoa. Our
      laboratory has correlated Crisp-1 binding to sperm with inhibiting the signaling
      cascades that initiate capacitation while others have shown that blocking Crisp-1
      binding sites on oocytes interferes with sperm-egg fusion. We hypothesize that
      the D and E populations of rat Crisp-1 have different interactions with sperm
      that modulate these distinct biological activities. Through tandem mass
      spectrometry (MS/MS) and monosaccharide composition analyses, we have identified
      at least one difference between the D and E forms as an additional single O
      linked N-acetyl galactosamine on an amino terminal threonine residue in Protein
      E. This post-translational modification appears to account for the unique 'E'
      epitope bound by monoclonal antibody 4E9 developed in our laboratory, and may
      also lead to differential processing and localization of Protein E on sperm, when
      compared to Protein D. These findings are the first step in distinguishing the
      molecular basis of the biological activities of the D and E forms of rat Crisp-1.
      The epididymal-specific expression of Crisp-1, combined with its role in
      regulation of sperm capacitation and oocyte interaction, make it an attractive
      target for post-testicular contraceptive development.

PMID- 16414183
TI  - Gonadotroph-specific expression of the human follicle stimulating hormone beta
      gene in transgenic mice.
AB  - A paucity of in vitro models has hampered studies of molecular mechanisms of FSH
      subunit gene expression. Consequently, we used an in vivo transgenic strategy to
      map the location of regulatory elements in the cloned 10 kb human FSHbeta gene.
      Analyses of transgenic mouse lines revealed that successive 5' truncations of the
      hFSHbeta promoter region to -350 bp relative to the transcriptional initiation
      site retained gonadotroph-specific expression and the sexually dimorphic pattern
      of male greater than female FSHbeta mRNA levels found normally in rodent
      pituitary. Truncation of the 3' flanking sequences from positions +3142 to +2138
      bp relative to the translational stop codon in exon 3 resulted in a complete loss
      of transgene expression, suggesting the presence of critical regulatory elements
      mapping to the 1 kb genomic segment downstream of position +2138, in addition to
      the proximal 5' promoter elements. In silico phylogenetic comparisons of
      mammalian FSHbeta genes revealed five islands of highly conserved sequence
      homology corresponding precisely to the proximal 5' promoter region, exon 2, the
      5' translated region of exon 3, and two regions at the 3' untranslated end of
      exon 3 that include putative polyadenylation and transcriptional termination
      signals. Sequence analyses of the 5' proximal promoter revealed the presence of
      several putative homeodomain binding sites as well as GATA, SMAD, AP-1, NF-1, NF
      Y and steroid hormone transcription factor binding sites within the highly
      conserved -350 bp promoter region. Notably absent from these 5' sequences,
      however, are consensus binding sites for either Egr-1 or Lim-2 transcription
      factors known to be critical for the gonadotroph-specific expression of the
      LHbeta gene. These findings support the hypothesis that one of the mechanisms
      underlying the differential regulation of the LHbeta, FSHbeta, and common alpha
      gonadotropin subunits within pituitary gonadotrophs may be differences in
      sequence-specific binding requirements for distinct combinations of transcription
      factors.

PMID- 16414182
TI  - KRAB: a partner for SRY action on chromatin.
AB  - The sex determining region Y (SRY/Sry) gene is necessary and sufficient for
      testis determination and differentiation in mammals. SRY/Sry encodes a putative
      transcription factor with a high mobility group (HMG) DNA-binding domain. The
      spatiotemporal regulation of Sry expression suggests that a brief action of SRY
      in a limited number of progenitor cells (pre-Sertoli cells) before the onset of
      default ovarian differentiation is sufficient to switch on testicular
      differentiation. Recent identification and characterization of the Kruppel
      associated box only (KRAB-O) protein as an SRY-interacting protein have provided
      experimental evidence supporting an interesting model for SRY function. In this
      model, SRY recruits the KRAB-KAP1 (KRAB-associating protein 1) complex as a
      chromatin modulator, which provides a molecular mechanism of SRY as a
      transcription factor. Moreover, the sufficiency of a brief action of SRY for
      testis differentiation can be partly explained by the heritability of KRAB
      mediated chromatin remodeling. Although it is currently uncertain whether KRAB-O
      is the only KRAB protein with which SRY interacts, we hypothesize that KRAB-O or
      yet-to-be identified KRAB-containing proteins might play various roles in sex
      determination and gonadal differentiation.

PMID- 16414185
TI  - A preliminary study on sorption, diffusion and degradation of mustard (HD) in
      cement.
AB  - A preliminary study has been done to examine the sorption, diffusion and
      degradation of mustard (HD) in cement. The sample of dried cement paste is a meso
      porous adsorbant with a BET surface area around 40.8 m2/g, which is able to
      adsorb vapor of HD at room temperature and to result in a multiple-layer isotherm
      of II type. The molecule of HD seemed to chemically adsorb onto cement surface.
      Droplet of HD contaminating cement was able to be degraded into less toxic
      products, but in a very low rate of k = 4.8 x 10(-5) min(-1) and t(1/2) = 16 x
      10(4) min at room temperature. Droplet of HD is able to penetrate through the
      layer of cement, but a cement plate of 8mm can protect against HD droplets over
      48 h. A decrease of thickness for cement layer or addition of sand in cement
      would lead to lower the protection time against HD droplets. The diffusion
      coefficient of HD molecule in cement was determined, about 1.3 x 10(-4) cm2/min
      and of a typical diffusion in solid.

PMID- 16414184
TI  - Critical role of CFTR in uterine bicarbonate secretion and the fertilizing
      capacity of sperm.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl
      channel expressed in a wide variety of epithelial cells, mutations of which are
      responsible for hallmark defective Cl- and HCO3- secretion seen in cystic
      fibrosis (CF). However, the physiological role of CFTR in reproductive tracts is
      far from understood although infertility has been observed in CF patients of both
      sexes. Previously we have demonstrated the expression of CFTR in the female
      reproductive tract and the involvement of CFTR in mediating anion secretion by
      the endometrium. Our recent results show that endometrial epithelial cells
      possess a cAMP-activated HCO3- transport mechanism, which could be impaired with
      channel blockers known to block CFTR or antisense against CFTR. Co-culture of
      sperm with CFTR antisense-treated endometrial cells or HCO3- secretion-defective
      CF epithelial cells resulted in reduced sperm capacitation and egg-fertilizing
      ability. Addition of HCO3- to the culture media and transfection of wild-type
      CFTR into CF cells rescued the fertilizing capacity of sperm. Immunostaining and
      Western blot revealed that CFTR is expressed in rodent sperm and intracellular
      measurement of pH during sperm capacitation indicated that the entry of HCO3-
      into sperm could be inhibited by CFTR inhibitor. These results are consistent
      with a critical role of CFTR in controlling uterine HCO3- secretion and sperm
      fertilizing capacity, suggesting that CFTR may be a potential target for post
      meiotic regulation of fertility.

PMID- 16414186
TI  - Circadian expression of clock genes is maintained in the liver of Vitamin A
      deficient mice.
AB  - In mammals, circadian oscillators exist not only in the central clock of the
      suprachiasmatic nucleus (SCN) but also in peripheral tissues such as the liver,
      heart and kidneys. Peripheral clocks are entrained to the SCN clock by both
      neural and humoral signals. Vitamin A might be one candidate that synchronizes
      peripheral clocks by activating its ligand-dependent nuclear receptors in
      mammals. The present study examines the effect of a Vitamin A deficiency on the
      circadian expression of clock genes in the mouse liver. Serum Vitamin A levels
      remained constant throughout the day in control mice, and were significantly
      reduced in Vitamin A-deficient mice. Northern blots showed that circadian
      expression of the clock genes mPer1, mPer2, Clock, and BMAL1, and of the clock
      controlled output gene D-site binding protein (DBP), was maintained in Vitamin A
      deficient mice. Our results suggest that dietary Vitamin A is not essential for
      generating circadian rhythms of peripheral clocks in mammals.

PMID- 16414187
TI  - Suppression of survival kinases and activation of JNK mediate ethanol-induced
      cell death in the developing rat brain.
AB  - Administration of ethanol to immature rat pups during the period in which
      synaptogenesis occurs triggers extensive apoptotic cell death in the brain. This
      ethanol-induced cell death is known to be mediated by Bax activation, which is
      caused by mitochondrial dysfunction. However, little data is available regarding
      the regulation of survival signaling pathways and their downstream events that
      lead to Bax activation. Thus, in the present study, we aimed to investigate the
      effect of ethanol on survival signaling pathways and their downstream events that
      lead to cell death in the rat brain during the brain developmental period.
      Ethanol (3 g/kg, 20% in saline) was administered subcutaneously to post-natal 7
      day-old rat pups twice at 2-h intervals and the pups were sacrificed at 4 h
      following the first ethanol injection. Ethanol treatment suppressed the
      activation of survival kinases, particularly Akt, Erk1/2 and PKAalpha, whereas it
      increased the activation of JNK. Moreover, dissociation of dephosphorylated Bad
      from 14-3-3 and the interaction of activated JNK with Bcl-2 were elevated by
      ethanol treatment. The present study demonstrated that ethanol treatment during
      the brain developmental period induced mitochondrial dysfunction, which led to
      cell death by the suppression of survival kinases, Bad release from 14-3-3 and
      inactivation of Bcl-2 by activated JNK.

PMID- 16414188
TI  - Seroprevalence of Toxoplasma gondii in captive felids in Thailand.
AB  - The prevalence of antibodies against Toxoplasma gondii was investigated by
      commercial latex agglutination test kit (Toxocheck-MT 'Eiken') in captive felids
      maintained at zoos and a wildlife breeding center in different geographic regions
      of Thailand. Sera from a total of 136 captive felids of 12 species was obtained
      between 2002 and 2004. The overall seroprevalence of T. gondii was found in 21 of
      136 (15.4%) felids. The titers varied from 1:64 (eight samples) to 1:8192 (one
      sample). The seroprevalence in different geographic regions were from 0% in the
      northern area to 23% in the southern area. This study suggested a widespread
      exposure of captive felids to T. gondii in Thailand and this is the first report
      of serologic analysis for T. gondii in captive felids in Southeast Asia.

PMID- 16414189
TI  - Application of molecular biology to the diagnosis of parasitic disease.
      Proceedings of the Third Annual Meeting of the European Veterinary Parasitology
      College (EVPC). May 27, 2005. Vilnius, Lithuania.

PMID- 16414190
TI  - Epidemiological studies on intestinal helminth parasites of the patagonian grey
      fox (Pseudalopex griseus) in Tierra del Fuego, Patagonia Argentina.
AB  - The present work was performed to study the intestinal helminths of the
      patagonian grey fox (Pseudalopex griseus) and to obtain information about its
      possible role in the sylvatic life cycle of Echinococcu granulosus in Tierra del
      Fuego, Patagonia Argentina. Eighty-one foxes were captured and subject to post
      mortem analysis. Thirty-one foxes (38.3%) harboured helminths. A total of six
      helminth species were recovered. Only one adult of E. granulosus was found in the
      studied samples. The current study is the first report of the intestinal
      helminths of the patagonian grey fox in Tierra del Fuego, Argentina and showed
      that this specie is probably not an important reservoir host for E. granulosus.

PMID- 16414191
TI  - Validation of molecular-diagnostic techniques in the parasitological laboratory.
AB  - Diagnostic laboratories today often operate according to standard quality
      management procedures such as ISO/IEC 17025. This requires that only validated
      methods are used. Validation procedures help to document that a particular
      protocol used by the accredited laboratory has a guaranteed performance in that
      particular laboratory. Several study designs exist for validation procedures.
      Computer programmes are available to help with the statistical analysis of
      validation results. The agreement beyond chance of results obtained in the
      protocol that is to be validated can be compared to those achieved in an already
      established test (agreement). For a method that is used under routine conditions
      or for epidemiological studies, it is necessary to assess the diagnostic
      sensitivity and diagnostic specificity of the technique. These parameters can be
      estimated by comparing the method that needs to be validated with an existing
      reliable method ('gold standard'). This is done by testing a standard set of well
      documented samples using both techniques in parallel. Approaches using Bayes'
      theorem are used to perform gold standard-free validations. Many PCR-based
      methods are characterised by an excellent analytical sensitivity and are thus
      good candidates for diagnostic tools of the required diagnostic sensitivity.
      However, the high level of analytical sensitivity can also make molecular
      techniques susceptible to cross-contamination and carry-over problems leading to
      false-positive results. Moreover, the presence of inhibitors can cause false
      negative results. After an initial validation, test performance needs to be
      continuously monitored, e.g. by using combined Shewhart-CUSUM control routines,
      and test results compared to those obtained by other laboratories (proficiency
      testing).

PMID- 16414192
TI  - Seroprevalence of Toxoplasma gondii antibodies in captive elephants (Elephaus
      maximus maximus) in Sri Lanka.
AB  - Serum samples collected during August 2003-June 2004 from 45 privately owned
      captive and 8 elephants from the Pinnawala Elephant Orphanage were tested for the
      presence of antibodies against Toxoplasma gondii using the direct modified
      agglutination test (MAT). Antibodies were found in sera of 14 of 45 (32%)
      privately owned elephants with titers of 1:25 in three, 1:50 in three, 1:100 in
      three, 1:200 in three, and 1:400 in three elephants. The elephants from Pinnawala
      Elephant Orphanage were seronegative. This is the first report of T. gondii
      seroprevalence in elephants in Sri Lanka.

PMID- 16414193
TI  - Texel sheep are more resistant to natural nematode challenge than Suffolk sheep
      based on faecal egg count and nematode burden.
AB  - Limited information is available on differences between sheep breeds with respect
      to helminth resistance under temperate conditions. The present study was designed
      to confirm and extend preliminary findings on observed breed differences in
      resistance to naturally acquired gastrointestinal nematodes in Suffolk and Texel
      sheep. Three trials were carried out. In trial 1 (1999-2003) lambs co-grazed from
      birth were faecal sampled at various time points up to 17 weeks of age. Worm
      burden was assessed at 17 weeks of age from a minimum of six lambs per breed in
      each of the 3 years. In trial 2, faecal egg count (FEC) was determined on six
      farms with co-grazed Suffolk and Texel purebred lambs. In trial 3 (2001-2003),
      ewes were faecal sampled at winter housing. In all three trials, an influence of
      breed on resistance to naturally acquired trichostrongyle infection was
      demonstrated. In trial 1, significantly higher FEC and worm burden was observed
      in Suffolk compared with Texel lambs following natural challenge. In trial 2, FEC
      recorded in lambs from six farms confirmed the breed differences previously
      observed. A breed difference in resistance to GI parasites was also observed in
      older ewes. In both breeds, an age effect on the FEC was observed with younger
      ewes having greater FEC than older ewes.

PMID- 16414194
TI  - A multicenter evaluation of the effectiveness of Quest Gel (2% moxidectin)
      against parasites infecting equids.
AB  - Controlled trials with a common protocol were conducted in Idaho, Illinois and
      Tennessee to evaluate anthelmintic effectiveness of Quest Gel (QG; 2% moxidectin)
      against lumenal parasites in horses. Candidate horses were required to have
      naturally acquired nematode infections, as confirmed by presence of strongylid
      eggs in feces. At each site, 24 equids were blocked on the basis of pretreatment
      strongyle fecal egg counts (EPG) and randomly assigned to treatments within
      blocks. Within each block of two animals, one received QG on Day 0 at a dosage of
      0.4 mg moxidectin/kg b.w. and one was an untreated control. Body weights measured
      the day before treatment served as the basis for calculating treatment doses.
      Horses assigned to treatment with QG received the prescribed dose administered
      orally with the commercially packaged Sure Dial syringe. Horses were necropsied
      12-14 days after treatment, and lumenal parasites and digesta were harvested
      separately from each of five organs, including the stomach, small intestine,
      cecum, ventral colon and dorsal colon. Parasites from stomachs and small
      intestines were identified to genus, species and stage. Micro- (i.e., < 1.5 cm)
      and macroparasites (i.e., > 1.5 cm) in aliquots from the cecum, ventral colon and
      dorsal colon were examined in aliquots of approximately 200 parasites until at
      least 600 parasites had been identified to genus, species and stage or until all
      parasites in the 5% aliquot were examined, whichever occurred first. Data were
      combined across sites and analyzed by mixed model analysis of variance to assess
      the fixed effect of treatment and random effects of site and block within site.
      Because QG does not contain a cestocide, efficacy of QG against tapeworms was not
      significant (P > 0.05). Based on geometric means, however, efficacy of QG was
      greater than 90% (P < 0.05) against 38 species and developmental stages of
      cyathostomes, strongyles, bots, larval pinworms and ascarids encountered in at
      least 6 of 36 control horses in the combined data set. None of the horses treated
      with moxidectin exhibited evidence of adverse effects. Study results demonstrate
      QG, administered to horses with naturally acquired endoparasite infections at a
      dosage of 0.4 mg moxidectin/kg b.w., was highly effective against a broad range
      of equine parasitic infections.

PMID- 16414195
TI  - Biological, seasonal and environmental factors associated with Pulex irritans
      infestation of dairy goats in Greece.
AB  - The objectives of the present study were to study the fauna of fleas infesting
      dairy goats in Greece, the spectrum of hosts each flea species infests, identify
      risk factors in the environment, and goat management practices that favour flea
      infestation of goats, and describe the seasonal variation of infestation in
      goats. For this purpose, a total of 64 herds, with a history of flea infestation
      in goats, were visited during June and July of 2002 for data collection on flea
      burdens, species of fleas on goats, and other farm or pet animal species in the
      farm. Also data were collected on herd characteristics and management along with
      the flea infestation status of the village where it was located through a
      questionnaire survey. Data on elevation and climatic characteristics of the
      villages where the herds were located were also used in the study. All fleas
      collected from goats, sheep, pigs, and cattle were identified as being Pulex
      irritans. All fleas collected from cats were identified as being Ctenocephalides
      felis. Dogs were infested either with P. irritans, C. canis, or C. felis, or with
      both C. canis and C. felis. Kids had a significantly higher flea burden than
      goats and the Skopelos breed had the highest flea burden of all breeds followed
      in diminishing order by the breeds Capra prisca, Saanen cross mix, and Alpine
      cross mix (p < 0.05). The gender of the animal had no significant effect on flea
      burden. Factors significantly affecting the flea burden of goats were duration of
      flea infestation in the herd, type of flea control, and manure imported prior to
      the appearance of fleas in the herd (p < 0.05). The flea burden of goats was
      highest during summer and lowest during winter (p < 0.01), with complete an
      absence of infestation in January and February. Finally, a significant difference
      (p < 0.05) was found between the average annual temperature of villages with flea
      infestation (15.59 degrees C) and villages without flea infestation (17.14
      degrees C). It was concluded that P. irritans was a true infestation of goats in
      Greece.

PMID- 16414196
TI  - Transmission of Leishmania infantum via blood transfusion in dogs: potential for
      infection and importance of clinical factors.
AB  - Blood transfusion is an important routine practice in veterinary medicine that
      generally involves the use of whole blood. Permanent blood donors must be
      vaccinated against viral infections that affect dogs and submitted periodically
      to clinical and serological examinations to detect blood-transmitted diseases.
      There is a very high risk of transmission of infectious agents, particularly
      protozoans due to their long incubation periods, subclinical persistence in
      infected animals and likelihood of remaining viable in bloodstocks. The aim of
      the present study was to identify the potential of asymptomatic and
      oligosymptomatic dogs for Leishmania infantum transmission as a result of
      transfusional practice. Nineteen Leishmania-seropositive adult dogs of both sexes
      and indeterminate breeds were selected as donors. The animals were classified as
      symptomatic, oligosymptomatic or asymptomatic after clinical examination and
      evaluated by ELISA, IFAT and bone marrow puncture biopsies. Whole blood and
      monocyte cells were collected and used for dog's serological evaluation and
      inoculation in culture medium as well as in hamsters. All but three dogs were
      positive for IFAT, ELISA and parasite demonstration in bone marrow aspirates,
      irrespective of their clinical conditions. Parasites were detected in 77% of the
      whole blood and 90% of the monocyte cultures. Six months after inoculation with
      whole blood or monocytes, hamsters developed infection and clinical symptoms of
      visceral leishmaniasis, as well as positive titres measured by ELISA. These
      results suggest that blood donors should be monitored periodically and rigorously
      for Leishmania infection, to prevent dissemination of the disease through blood
      transfusion.

PMID- 16414197
TI  - Meta-analysis of early excision of burns.
AB  - AIMS: This meta-analysis sought to establish if early excision and grafting is
      better or equivalent to the conservative treatment of burns in both children and
      adults with minor or major burns. The outcomes of interest are mortality, wound
      healing time, duration of sepsis, operating hours, complications of surgery,
      length of hospital stay, blood transfusion requirements and long term morbidity
      like joint contractures and hypertrophic scarring. METHODS: We searched MEDLINE
      (1966-July 2004), EMBASE (1980-August 2004) and the Cochrane Central Register of
      Controlled Trials (CENTRAL) with the keywords 'early excision' and 'burns'. This
      yielded 441 articles of which 15 were randomized controlled trials. Only six
      trials met the inclusion criteria. RESULTS: There was a significant reduction in
      mortality with early excision of burns when compared with traditional treatment
      only in patients without inhalational injury (RR 0.36, 95% CI 0.20 to 0.65). The
      blood transfusion requirement is significantly higher in the early excision group
      but the length of hospital stay was significantly shorter (WMD -8.89, 95% CI 
      14.28 to -3.50). There was no conclusive evidence on the difference between the
      two groups in terms of duration of sepsis, wound healing time and skin graft
      take. CONCLUSION: Early excision of burns is beneficial in reducing mortality (in
      patients without inhalational injury), length of hospital stay. The only drawback
      is the greater volume of blood loss.

PMID- 16414198
TI  - Adeno-associated virus vectors serotyped with AAV8 capsid are more efficient than
      AAV-1 or -2 serotypes for widespread gene delivery to the neonatal mouse brain.
AB  - Adeno-associated virus (AAV) vectors have gained a preeminent position in the
      field of gene delivery to the normal brain through their ability to achieve
      extensive transduction of neurons and to mediate long-term gene expression with
      no apparent toxicity. In adult animals direct infusion of AAV vectors into the
      brain parenchyma results in highly efficient transduction of target structures.
      However AAV-mediated global delivery to the adult brain has been an elusive goal.
      In contrast, widespread global gene delivery has been obtained by i.c.v.
      injection of AAV1 or AAV2 in neonates. Among the novel AAV serotypes cloned and
      engineered for production of recombinant vectors, AAV8 has shown a tremendous
      potential for in vivo gene delivery with nearly complete transduction of many
      tissues in rodents after intravascular infusion. Here we compare the efficiency
      of an AAV8 serotyped vector with that of AAV1 and AAV2 serotyped vectors for the
      extent of gene delivery to the brain after neonatal injection into the lateral
      ventricles. The vectors all encoded green fluorescent protein (GFP) under control
      of a hybrid CMV enhancer/chicken beta-actin promoter with AAV2 inverted terminal
      repeats, but differed from each other with respect to the capsid type. A total of
      6.8 x 10(10) genome copies were injected into the lateral ventricles of postnatal
      day 0 mice. Mice were killed at postnatal day 30 and brains analyzed for
      distribution of GFP-positive cells. AAV8 proved to be more efficient than AAV1 or
      AAV2 vectors for gene delivery to all of the structures analyzed, including the
      cerebral cortex, hippocampus, olfactory bulb, and cerebellum. Moreover the
      intensity of gene expression, assessed using a microarray reader, was
      considerably higher for AAV8 in all structures analyzed. In conclusion, the
      enhanced transduction achieved by AAV8 compared with AAV1 and AAV2 indicates that
      AAV8 is the superior serotype for gene delivery to the CNS.

PMID- 16414199
TI  - Gene expression profiling and analysis of signaling pathways involved in priming
      and differentiation of human neural stem cells.
AB  - Human neural stem cells have the ability to differentiate into all three major
      cell types in the CNS including neurons, astrocytes and oligodendrocytes. The
      multipotency of human neural stem cells shed a light on the possibility of using
      stem cells as a therapeutic tool for various neurological disorders including
      neurodegenerative diseases and neurotrauma that involve a loss of functional
      neurons. We have discovered previously a priming procedure to direct primarily
      cultured human neural stem cells to differentiate into almost pure neurons when
      grafted into adult CNS. However, the molecular mechanism underlying this
      phenomenon is still unknown. To unravel transcriptional changes of human neural
      stem cells upon priming, cDNA microarray was used to study temporal changes in
      human neural stem cell gene expression profile during priming and
      differentiation. As a result, transcriptional levels of 520 annotated genes were
      detected changed in at least at two time points during the priming process. In
      addition, transcription levels of more than 3000 hypothetical protein encoding
      genes and EST genes were modulated during the priming and differentiation
      processes of human neural stem cells. We further analyzed the named genes and
      grouped them into 14 functional categories. Of particular interest, key cell
      signal transduction pathways, including the G-protein-mediated signaling pathways
      (heterotrimeric and small monomeric GTPase pathways), the Wnt signaling pathway
      and the TGF-beta pathway, are modulated by the neural stem cell priming,
      suggesting important roles of these key signaling pathways in priming and
      differentiation of human neural stem cells.

PMID- 16414201
TI  - Confirming alcohol-moderated links between cannabis use and dependence in a
      national sample.
AB  - The present study confirmed findings that alcohol moderates the link between
      cannabis use and dependence. The study examined a large, diverse national sample
      of 856 people who consumed cannabis and alcohol at least twice per week. The
      study possesses several methodological improvements over past research, including
      less subjective measures of cannabis use and interview-based data collection.
      Cannabis use and alcohol consumption interacted to predict cannabis dependence
      symptoms. Cannabis use covaried with cannabis dependence particularly in people
      who consumed greater amounts of alcohol. These data further support the
      hypothesis that alcohol increases problems associated with cannabis use.

PMID- 16414200
TI  - Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant
      ectonucleotidase expressed by rat astrocytes.
AB  - Inflammatory and degenerative pathophysiological processes within the CNS are
      important causes of human disease. Astrocytes appear to modulate these reactions
      and are a major source of inflammatory mediators, e.g. extracellular adenine
      nucleotides, in nervous tissues. Actions following extracellular nucleotides
      binding to type 2 purinergic receptors are regulated by ectonucleotidases,
      including members of the CD39/ecto-nucleoside triphosphate diphosphohydrolase
      family. The ectonucleotidases of astrocytes expressed by rat brain rapidly
      convert extracellular ATP to ADP, ultimately to AMP. RT-PCR, immunocytochemistry
      as well as Western blotting analysis demonstrated expression of multiple ecto
      nucleoside triphosphate diphosphohydrolase family members at both the mRNA and
      protein level. By quantitative real-time PCR, we identified Entpd2 (CD39L1) as
      the dominant Entpd gene expressed by rat hippocampal, cortical and cerebellar
      astrocytes. These data in combination with the elevated ecto-ATPase activity
      observed in these brain regions, suggest that NTPDase2, an ecto-enzyme that
      preferentially hydrolyzes ATP, is the major ecto-nucleoside triphosphate
      diphosphohydrolase expressed by rat astrocytes. NTPDase2 may modulate
      inflammatory reactions within the CNS and could represent a useful therapeutic
      target in human disease.

PMID- 16414202
TI  - A paracrine component of salient symptoms of depression in Cushing's of
      diencephalic origin, and in perimenstrual syndromes: a hypothesis.
AB  - Interrelationships between adrenocortical secretions and depression syndromes
      have been known since early in the 20th century. Now, the fact that pregnane and
      pregnene steroids are also known to be synthesized in the brain (they are termed
      neurosteroids (NS)), raises the possibility that these natural compounds could
      have paracrine effects. Adrenocorticotropic hormone (ACTH) can modulate
      biosynthesis of NSs. 17beta estradiol has been shown to decrease THP
      concentration in the brain. It is hypothesized that imbalance between stimulatory
      and depressant NSs induced by ACTH elevation in hypothalamo pituitary dependent
      Cushing's, and by estrogen concentration changes during the menstrual cycle, may
      be associated with the pathophysiology of salient symptoms of depression in
      Cushing's and in perimenstrual syndromes.

PMID- 16414203
TI  - The unified hypothesis of interactions among the bone, adipose and vascular
      systems: 'osteo-lipo-vascular interactions'.
AB  - Epidemiological evidence has established a link among hyperlipidemia, visceral
      obesity, osteoporosis, and cardiovascular diseases (CVD). We here propose the
      hypothesis that the associations of those disorders are based on interaction of
      the three organs, i.e. the bone, adipose, and vascular tissues, possibly through
      multiple interactions among several humoral factors and/or transcription factors.
      The unified hypothesis of three organs, which we call 'osteo-lipo-vascular
      interactions', may be explained by the common origin of the cells in each organ.
      The mesenchymal stem cells are capable of differentiating into osteoblasts,
      vascular smooth muscle cells, and adipocytes. Alternatively, macrophages may
      evolve into osteoclasts or infiltrate both the vascular and adipose tissues,
      thereby leading to chronic inflammation. This unified concept of three organs may
      provide insights into the development of a new drug for the treatment of
      osteoporosis, obesity, hyperlipidemia or CVD.

PMID- 16414204
TI  - A new classification system of anticancer drugs - based on cell biological
      mechanisms.
AB  - The arrival of a great number of new anticancer agents has made it necessary to
      reclassify all of them. We established a new classification system based on cell
      biological mechanisms. Anticancer drugs were grouped as cytotoxic drug and
      modifier, which could regulate the interaction of tumor, host and drugs. The
      modifiers were subdivided into three groups: cell biological modifier which
      reverses the abnormal biological behaviour of tumor cells, biological response
      modifier which regulates the host response of tumor and biochemical modulator
      which affects the host's metabolic pathway of cytotoxic drug to enhance the
      chemosensitivity or reduce the adverse reaction. Combination with cell biological
      modifiers and cytotoxic drugs play a double role of killer and rectifier for
      tumor cells, whereas biological response modifiers and cytotoxic drugs are
      combined to regulate the tumor-host interaction. Biochemical modulators and
      cytotoxic drugs are combined to enhance the chemosensitivity or improve the dose
      of cytotoxic drugs.

PMID- 16414205
TI  - Compromised local control due to treatment interruptions and late treatment
      breaks in early glottic cancer: Population-based outcomes study supporting need
      for intensified treatment schedules.
AB  - PURPOSE: This population-based study describes the treatment of early glottic
      cancer in Ontario, Canada and assesses whether treatment variations were
      associated with treatment effectiveness. METHODS AND MATERIALS: We studied 491
      T1N0 and 213 T2N0 patients. Data abstracted from charts included age, sex, stage,
      treatment details, disease control, and survival. RESULTS: The total dose ranged
      from 50 to 70 Gy, and the daily dose ranged from 1.9 to 2.8 Gy. In 90%, treatment
      duration was between 25 and 50 days. Field sizes, field reductions, beam
      arrangement, and beam energy varied. Late treatment breaks occurred in 13.6% of
      T1N0 and 27.1% of T2N0 cases. Local control was comparable to other reports for
      T1N0 (82% at 5 years), but was only 63.2% in T2N0. Variables associated with
      local failure in T1N0 were age less than 49 years (relative risk [RR], 3.21; 95%
      confidence interval [CI], 1.49-6.90) and >3 treatment interruption days (RR,
      2.43; 95% CI, 1.00-5.91). In T2N0, these were field reduction (RR, 2.33; 95% CI,
      1.23-4.42) and late treatment breaks (RR, 2.19; 95% CI, 1.09-4.41). CONCLUSION:
      Some aspects of treatment for early glottic cancer were associated with worse
      local control. Problems with protracted treatment are of particular concern,
      underscoring the need for randomized studies to intensify radiotherapy.

PMID- 16414206
TI  - Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer
      in patients previously irradiated to the pelvis: A multicentric phase II study.
AB  - PURPOSE: The combination of irradiation and total mesorectal excision for rectal
      carcinoma has significantly lowered the incidence of local recurrence. However, a
      new problem is represented by the patient with locally recurrent cancer who has
      received previous irradiation to the pelvis. In these patients, local recurrence
      is very often not easily resectable and reirradiation is expected to be
      associated with a high risk of late toxicity. The aim of this multicenter phase
      II study is to evaluate the response rate, resectability rate, local control, and
      treatment-related toxicity of preoperative hyperfractionated chemoradiation for
      locally recurrent rectal cancer in patients previously irradiated to the pelvis.
      METHODS AND MATERIALS: Patients with histologically proven pelvic recurrence of
      rectal carcinoma, with the absence of extrapelvic disease or bony involvement and
      previous pelvic irradiation with doses < or =55 Gy; age > or =18 years;
      performance status (PS) (Karnofsky) > or =60, and who gave institutional review
      board-approved written informed consent were treated by preoperative
      chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2)
      including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy
      (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the
      same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8
      Gy). During the radiation treatment, concurrent chemotherapy was delivered (5
      fluorouracil, protracted intravenous infusion, 225 mg/m(2)/day, 7 days per week).
      Four to 6 weeks after the end of chemoradiation, patients were evaluated for
      tumor resectability, and, when feasible, surgical resection of recurrence was
      performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy
      was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every
      3 weeks, for a total of 5 cycles. Patients were staged using the computed
      tomography (CT)-based F-classification (F0: no side-wall involvement; F1, F2, F3:
      1, 2, and 3-4 side-walls involved, respectively). Toxicity was evaluated on the
      basis of the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Fifty
      nine patients (38 male, 21 female; median age, 62 years; range, 43-77 years) were
      enrolled in the study, by 12 different Italian radiotherapy departments. Previous
      surgery was anterior resection in 45 patients (76.3%) and abdominal-perineal
      resection in 14 patients (23.7%); previous radiotherapy dosage ranged between 30
      and 55 Gy (median, 50.4 Gy); the median interval between prior radiation therapy
      to the onset of reirradiation was 27 months (range, 9-106 months); 44 patients
      (74.6%) had received some form of previous chemotherapy (concurrent and/or
      adjuvant). Fifty-one of 59 patients (86.4%) completed chemoradiation without
      treatment interruptions: 6 patients (10.2%) had temporary treatment interruption
      due to toxicity or patient compliance, and 2 patients (3.4%) had definitive
      treatment interruption. The incidence of Grade 3 lower gastrointestinal acute
      toxicity was only 5.1%. No patient developed Grade 4 acute toxicity. After
      chemoradiation, 5 patients (8.5%) had complete response (CR), 21 patients (35.6%)
      had partial response (PR), 31 patients (52.6%) had no change (NC) and 2 patients
      (3.4%) showed progressive disease (PD). Overall, the response rate (PR + CR) was
      44.1% (95% confidence interval, 29.0-58.9%). Twenty of 24 patients (83.3%) with
      pelvic pain before treatment had symptomatic response. Tumor resection was
      performed in 30 of 59 patients (50.8%) including 2 local excisions, 4 anterior
      resections, 18 abdominoperineal resections, and 6 other. Surgical resection
      resulted as R0 and R1 in 21 patients (35.6%) and 3 patients (5.1%), respectively.
      The possibility of radical resection was influenced by tumor response to
      chemoradiation (PD/NC: 7/33; PR/CR: 14/26; p = 0.009). Thirty-three patients
      received adjuvant chemotherapy, which was completed in 30 (50.8%). At a median
      follow-up of 36 months (range, 9-69 months), 28 patients (47.5%) developed local
      recurrence or tumor progression in the unresected pelvic disease and 18 patients
      (30.5%) developed distant metastasis. Seven patients showed late toxicity,
      including 2 skin fibrosis, 2 impotence, 2 urinary complications requiring
      nephrostomy, and 1 small bowel fistula requiring surgical diversion. Overall
      median survival was 42 months. Five-year actuarial survival was 39.3%; 66.8% in
      R0 resected patients and 22.3% in patients treated without surgery or undergoing
      subtotal tumor removal. Local control and disease-free survival were
      significantly correlated with the interval between surgical treatment for primary
      tumor and local recurrence (p = 0.028 and p = 0.003, respectively). Radical
      resection significantly influenced local control, disease-free survival, and
      overall survival (p = 0.010, p = 0.010, and p = 0.050 respectively). The
      multivariate analysis confirmed the impact of surgery-relapse interval on local
      control (p = 0.016) and disease-free survival (p = 0.002), and confirmed the
      correlation between R0 surgery with local control and disease-free survival (p =
      0.016). CONCLUSIONS: Use of hyperfractionated chemoradiation was associated with
      a low rate of acute toxicity and an acceptable incidence of late complications.
      Pain control was excellent. The overall 5-year survival was 39%. Despite 87.4% of
      patients having F1-3 stage disease, approximately one-third (35%) achieved R0
      resection, and two-thirds of patients in this cohort of patients were alive at
      the 5-year mark. However, further studies using innovative treatment algorithms
      are warranted to, hopefully, improve the local tumor response and control.

PMID- 16414207
TI  - Adverse event reporting and developments in radiation biology after normal tissue
      injury: International Atomic Energy Agency consultation.
AB  - PURPOSE: Recent research has enhanced our understanding of radiation injury at
      the molecular-cellular and tissue levels; significant strides have occurred in
      standardization of adverse event reporting in clinical trials. In response, the
      International Atomic Energy Agency, through its Division of Human Health and its
      section for Applied Radiation Biology and Radiotherapy, organized a consultation
      meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology,
      normal tissue reactions, and adverse event reporting. METHODS AND MATERIALS:
      Representatives from cooperative groups of African Radiation Oncology Group,
      Curriculo Radioterapeutica Ibero Latino Americana, European Organization for
      Research and Treatment of Cancer, National Cancer Institute of Canada Clinical
      Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation
      Oncology Group held the meeting discussion. RESULTS: Representatives of major
      radiotherapy groups/organizations and prominent leaders in radiotherapy discussed
      current understanding of normal tissue radiobiologic effects, the design and
      implementation of future clinical and translational projects for normal tissue
      injury, and the standardization of adverse-event reporting worldwide.
      CONCLUSIONS: The consensus was to adopt NCI comprehensive adverse event reporting
      terminology and grading system (CTCAE v3.0) as the new standard for all
      cooperative group trials. Future plans included the implementation of coordinated
      research projects focusing on normal tissue biomarkers and data collection
      methods.

PMID- 16414208
TI  - Localized volume effects for late rectal and anal toxicity after radiotherapy for
      prostate cancer.
AB  - PURPOSE: To identify dosimetric parameters derived from anorectal, rectal, and
      anal wall dose distributions that correlate with different late gastrointestinal
      (GI) complications after three-dimensional conformal radiotherapy for prostate
      cancer. METHODS AND MATERIALS: In this analysis, 641 patients from a randomized
      trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation
      Therapy Oncology Group/European Organization for the Research and Treatment of
      Cancer (RTOG/EORTC) criteria and five specific complications. The variables
      derived from dose-volume histogram of anorectal, rectal, and anal wall were as
      follows: % receiving > or =5-70 Gy (V5-V70), maximum dose (Dmax), and mean dose
      (D(mean)). The anus was defined as the most caudal 3 cm of the anorectum.
      Statistics were done with multivariate Cox regression models. Median follow-up
      was 44 months. RESULTS: Anal dosimetric variables were associated with RTOG/EORTC
      Grade > or =2 (V5-V40, D(mean)) and incontinence (V5-V70, D(mean)). Bleeding
      correlated most strongly with anorectal V55-V65, and stool frequency with
      anorectal V40 and D(mean). Use of steroids was weakly related to anal variables.
      No volume effect was seen for RTOG/EORTC Grade > or =3 and pain/cramps/tenesmus.
      CONCLUSION: Different volume effects were found for various late GI
      complications. Therefore, to evaluate the risk of late GI toxicity, not only
      intermediate and high doses to the anorectal wall volume should be taken into
      account, but also the dose to the anal wall.

PMID- 16414209
TI  - Neural circuits underlying circadian behavior in Drosophila melanogaster.
AB  - Circadian clocks include control systems for organizing daily behavior. Such a
      system consists of a time-keeping mechanism (the clock or pacemaker), input
      pathways for entraining the clock, and output pathways for producing overt
      rhythms in behavior and physiology. In Drosophila melanogaster, as in mammals,
      neural circuits play vital roles in all three functional subdivisions of the
      circadian system. Regarding the pacemaker, multiple clock neurons, each with cell
      autonomous pacemaker capability, are coupled to each other in a network. The
      outputs of different sets of clock neurons in this network combine to produce the
      normal bimodal pattern of locomotor activity observed in Drosophila. Regarding
      input, multiple sensory modalities (including light, temperature, and pheromones)
      use their own circuitry to entrain the clock. Regarding output, distinct circuits
      are likely involved for controlling the timing of eclosion and for generating the
      locomotor activity rhythms. This review summarizes work on all of these circadian
      circuits, and discusses the broader utility of studying the fly's circadian
      system.

PMID- 16414211
TI  - Host and bacterial factors in listeriosis pathogenesis.
AB  - Members of the Genus Listeria are ubiquitous environmental saprophytic
      microorganisms. If ingested they can cause a severe disseminated disease
      (listeriosis) that has a high mortality rate, the highest of any food-borne
      pathogen, even with antibiotic therapy. Central to the high mortality rate is the
      hallmark characteristic of the microorganism to grow intracellularly. The
      presence of listeriae in food processing plants has resulted in many outbreaks of
      human disease and large scale recalls of processed foods. Despite the ubiquity of
      the microorganism, the actual disease rate (those animals showing disease signs
      over those exposed) is quite low and disease is almost always associated with an
      underlying predisposition (pregnancy being the most common in otherwise normal
      individuals). There are many features of the pathogenesis of listeriosis that
      have remained mysterious despite the extensive use of the microorganism in the
      study of cell-mediated immunity and intracellular growth. Informational advances
      such as the sequence of the mouse and listerial genomes, and technical advances
      such as the discovery of listeria-susceptible mouse strains, may renew interest
      in the study of the natural pathogenesis of the disease. This may be further
      facilitated by studies that employ the natural inoculation route and mimic common
      predisposing conditions witnessed in victims of natural outbreaks.

PMID- 16414210
TI  - Time-sharing in pigeons: Independent effects of gap duration, position and
      discriminability from the timed signal.
AB  - Previous data suggest that in a peak-interval procedure with gaps, memory for the
      pre-gap interval varies with the discriminability of the gap from the to-be-timed
      signal. Here we extend this finding by manipulating the pre-gap and gap intervals
      as well as the visual contrast between the gap and the to-be-timed signal. The
      delay in response function after the gap was found to vary with the duration and
      position of the gap. However, for each gap duration and position, the delay in
      response increased with the gap-signal contrast: at 60% gap-signal contrast
      pigeons continued to accumulate time during the gap, at 80% gap-signal contrast
      pigeons stopped timing during the gap, and at 100% gap-signal contrast pigeons
      reset their timing after the gap. Data are accounted for by a time-sharing model
      assuming two concurrent processes during the gap--time accumulation and memory
      decay controlled by the salience of the gap--whose interplay results in a
      continuum of responses in the gap procedure.

PMID- 16414212
TI  - Use of PCR-restriction fragment length polymorphism for the identification of
      zoonotic mycobacteriosis in zebrafish caused by Mycobacterium abscessus and
      Mycobacterium chelonae.
AB  - Skin ulcers, scoliosis, and dropsy-like scale edema were observed in laboratory
      maintained zebrafish. Affected fish had multifocal granulomas not only in
      internal organs such as the liver, intestine, genital organs, kidney, muscle, and
      spleen but also in the fin, epithelium, gills, and sclera of the eyes. Large
      numbers of acid-fast-rod-shaped bacteria were observed within the necrotic
      centers of well-demarcated, multifocal granulomas with Gram's stain and Ziehl
      Neelson's stain. The size of the Mycobacterium spp. was 1-2 microm x 2-3 microm
      with a double-layered cell wall, based upon electron-microscopical features.
      Definitive diagnosis of these outbreaks was obtained by culture on selective
      media followed by PCR-restriction fragment length polymorphism analysis (PRA) of
      the rpoB gene for species identification. The amplified 360-bp products of the
      rpoB gene of mycobacteria isolated from zebrafish were digested with MspI
      restriction enzyme, which revealed unique band patterns matching those of
      Mycobacterium abscessus and Mycobacterium chelonae which are responsible for skin
      and soft tissue infection caused by rapidly growing mycobacteria in humans. This
      is the first documentation of the precise identification of zoonotic non
      tuberculous mycobacteria isolated from laboratory-maintained zebrafish by the PRA
      of the rpoB gene; this study thus provides a great deal of useful epidemiological
      information and reduces the likelihood that epizootics will occur.

PMID- 16414213
TI  - Expression of heat shock protein70 in pig oocytes: heat shock response during
      oocyte growth.
AB  - The heat shock response of growing and fully-grown pig oocytes was analyzed in
      vitro by determining heat shock protein70 (HSP70) synthesis under both normal
      conditions (39 degrees C; 0 and 6h) and after heat shock (43 degrees C; 1, 4 and
      6h). The expression of HSP70 in oocytes was detected by immunoblotting analysis.
      Growing oocytes measuring 80-99 microm synthesized a high number of HSP70 without
      heat shock effect, and these were capable of increasing the synthesis of HSP70
      after heat shock to a maximum after 1h. Growing oocytes measuring 100-115 microm
      also synthesized HSP70 without heat shock and after it, but the HSP70 synthesis
      was not statistically changed by increasing duration of heat shock. In fully
      grown oocytes, great amounts of HSP70 were found without heat shock treatment,
      and the contents of HSP70 significantly decreased after heat shock. These results
      indicate that growing oocytes are able to synthesize HSP70 after heat shock. This
      ability declines at the end of the growth period, and fully-grown oocytes are
      unable to induce HSP70 synthesis after heat shock. HSP70 is synthesized and
      stored during oocyte growth. The high HSP70 synthesis in non-heat-treated growing
      oocytes and a great amount of HSP70 in fully-grown oocytes support the hypothesis
      that HSP70 is important for oocyte growth and maturation.

PMID- 16414214
TI  - The reproductive cycle of male catfish Pseudoplatystoma fasciatum (Teleostei,
      Pimelodidae) revealed by changes of the germinal epithelium. An approach
      addressed to aquaculture.
AB  - The aims of the present study were to analyze the gonadal structure of
      Pseudoplatystoma fasciatum males during their annual cycle to enhance
      understanding of their reproductive biology and to improve the hormonally induced
      reproduction and culture of this species in hatcheries. We adopted the recently
      proposed method that establishes reproductive classes that are based on
      variations of the germinal epithelium within the year. Five reproductive classes
      were established: maturation (early, middle, and late), regression and
      recrudescence. Our observations revealed that in the spawning season P. fasciatum
      testes display two main functions: sperm production and sperm storage. We also
      concluded that the analysis of the variation of germinal epithelium was
      satisfactory when applied to this freshwater catfish and should be adopted for
      other fish species.

PMID- 16414215
TI  - Soy isoflavones affect platelet thromboxane A2 receptor density but not plasma
      lipids in menopausal women.
AB  - OBJECTIVES: It has been suggested that isoflavones protect the cardiovascular
      system, in part by improving lipid profile. The purpose of the present research
      was to examine the effect of a 12-week soy isoflavone supplementation on
      lipoprotein status and platelet thromboxane A2 receptor density. METHODS: Twenty
      nine healthy postmenopausal women were invited to take part in a randomised study
      to receive either 100 mg/day isoflavone supplement (n=15) or identical placebo
      capsules (n=14). Blood samples obtained at baseline and after 12 weeks were
      analysed for isoflavones, total cholesterol, high density lipoprotein
      cholesterol, triglycerides, glucose, insulin, estradiol, testosterone,
      gonadotrophins, sex hormone-binding globulin (SHBG) and platelet thromboxane A2
      receptor density. Blood pressure measurements, body mass index, subcutaneous fat
      at entrance and at the end of treatment were also registered. Changes in
      variables between groups were compared by ANOVA for repeated measures. RESULTS:
      Blood pressure, body mass index, subcutaneous fat, insulin, serum lipoprotein,
      sex hormones and SHBG did not differ among groups. However, platelet thromboxane
      A2 receptor density declined significantly (from 181.9+/-30.9 to 115.2+/-16.2
      fmol/10(8) platelets) in the experimental group, remaining mostly unchanged in
      the placebo group (176.3+/-27.3 to 170.4+/-28.2 fmol/10(8) platelets). The
      dissociation constant (Kd) values were unchanged. The change in platelet
      thromboxane A2 receptors correlated negatively with isoflavones serum
      concentration (r=-0.59, p<0.001). CONCLUSIONS: In this study we demonstrated that
      the beneficial effects of isoflavones in menopausal women could be more related
      to platelet function than to improving classical cardiovascular risk factors.

PMID- 16414216
TI  - Are endometrial polyps from pre-menopausal women similar to post-menopausal
      women? An immunohistochemical comparison of endometrial polyps from pre- and post
      menopausal women.
AB  - OBJECTIVE: Do endometrial polyps from pre- and post-menopausal women have similar
      immunohistochemical expression of oestrogen and progesterone receptors (ER, PR)
      and markers of cellular proliferation/apoptosis (Ki67 and Bcl-2). DESIGN:
      Prospective cohort study. Non-parametric statistical analysis was used. SETTING:
      Polyps recruited from women attending an out-patient hysteroscopy clinic in a UK
      district general hospital. PATIENTS: Fourteen pre-menopausal and 16 post
      menopausal women who presented with abnormal bleeding with endometrial polyps.
      INTERVENTIONS: Immunohistochemical staining was performed on endometrial polyps.
      MAIN OUTCOME MEASURES: Significant differences or correlations between hormone
      receptor expression (oestrogen and progesterone) and cell growth indices (Ki67
      and Bcl-2). RESULTS: Endometrial polyps from pre- and post-menopausal women had
      significant differences in their expression of hormone receptors and Ki67.
      However, polyps from both groups of women had similarly increased levels of Bcl
      2, an inhibitor of apoptosis. CONCLUSIONS: Pre- and post-menopausal polyps
      exhibit differing hormone receptor and proliferation markers, presumably a result
      of their hormonal milieu. However, both groups appear to have lost the usual
      control mechanisms for apoptotic regulation, this appears to be responsible for
      their growth.

PMID- 16414217
TI  - PLGA microcapsules with novel dimpled surfaces for pulmonary delivery of DNA.
AB  - We describe the fabrication of DNA-loaded poly(lactic-co-glycolic acid) (PLGA)
      microcapsules with novel surface morphologies that will be of use in pulmonary
      delivery. Our approach was to examine surface morphology and DNA encapsulation
      efficiency as a function of primary emulsion stability; using two surfactant
      series based on hydrophile-lipophile balance and hydrophobe molecular weight.
      Hydrophilic non-ionic surfactants yielded the most stable water-in
      dichloromethane emulsions (HLB values >8). These surfactants normally favor
      convex (o/w) interfacial curvatures and therefore this atypical behavior
      suggested a relatively high surfactant solvation in the dichloromethane 'oil'
      phase. This was consistent with the large fall in the glass transition
      temperature for microspheres prepared with Tween 20, which therefore efficiently
      penetrated the PLGA matrix and acted as a plasiticizer. Blends of Pluronic
      triblock copolymers performed poorly as water-in-dichloromethane emulsifiers, and
      were therefore used to generate hollow microspheres ('microcapsules') with low
      densities (0.24 g/cm(3)). Although the Pluronic-stabilized emulsions resulted in
      lower DNA loading (15-28%), microspheres (approximately 8 microm) with novel
      dimpled surfaces were fabricated. The depth and definition of the dimples was
      greatest for triblock copolymers with high MW hydrophobe blocks. By cascade
      impaction, the geometric mean weight diameter of the microcapsules was 3.43
      microm, suggesting that they will be of interest as biodegradable pulmonary
      delivery vehicles.

PMID- 16414218
TI  - Dissolution characteristics of cylindrical particles and tablets.
AB  - In this paper, dissolution characteristics of primary-particles and compressed
      tablets were investigated by experiments using a mathematical model. For the
      primary-particle, it was found that the dissolution rate increased with a
      decrease in the particle size. Assuming that primary-particles of size
      distribution were of cylindrical shape and that the dissolution occurs from the
      total external surface, an extended Nernst-Noyes-Whitney equation fitted to the
      experimental data well. As the influences of particle size and shape on thickness
      of a diffusion-boundary film were found to be quite low, the dissolution rate was
      considered to be affected by the specific surface area dominantly. Furthermore,
      the same model was applied to a compressed tablet and fitted to the data well.
      Though the rate constant obtained were not affected by the properties of primary
      particles forming the tablet, it was found to increase with the apparent voidage
      which occupies the inter-particle volume of tablet diluent among less soluble
      particles. Consequently, an increase in the apparent voidage is presumed to
      accelerate penetration of water into the internal voids of the tablet. Thus, the
      dissolution going, the effective surface area inside the tablet is considered to
      be extended.

PMID- 16414219
TI  - Synthesis and characterization of membranes obtained by graft copolymerization of
      2-hydroxyethyl methacrylate and acrylic acid onto chitosan.
AB  - Chitosan based membranes to be applied on wound healing as topical drug delivery
      systems were developed by graft copolymerization of acrylic acid (AA) and 2
      hydroxyethyl methacrylate (HEMA) onto chitosan using cerium ammonium nitrate as
      chemical initiator. Evidence for graft copolymerization of the vinyl monomers
      onto chitosan was obtained by FTIR and DMTA. Swelling degree, cytotoxicity,
      thrombogenicity and haemolytic activity of these membranes were evaluated.
      Chitosan-graft-AA-graft-HEMA showed to be the best matrix for drug delivery
      systems than chitosan-graft-AA because it retains good swelling properties, but
      the content in HEMA has improved cytocompatibility, hemocompatibility and
      thrombogenic character.

PMID- 16414220
TI  - Effects of conditions for preparing nanoparticles composed of aminoethylcarbamoyl
      beta-cyclodextrin and ethylene glycol diglycidyl ether on trap efficiency of a
      guest molecule.
AB  - Nanoparticles comprising copolymers of aminoethylcarbamoyl-beta-cyclodextrin (AEC
      beta-CD) and ethylene glycol diglycidyl ether (EGDGE) are prepared by an
      interfacial polyaddition reaction in a miniemulsion system. Polymers are formed
      in a W/O emulsion containing 0.25-10.0% (w/w) water and 5.0% (w/w) surfactant (MO
      3S, tetraglycerin monoester, HLB 8.8), where simple particles are predominantly
      obtained when the water content is 1.0% and 5.0%. Notably, nano-size small
      particles (diameter: 0.3 microm) are formed under the condition of 5.0% water and
      5.0% surfactant, which have the highest beta-CD contents (75.5 wt.%) and the most
      positive zeta-potential (53.6 mV). The zeta-potential measurement indicates that
      the obtained particles have positive charge due to protonation of their amino
      groups below around pH 10. Actually, uptake of 8-anilino-1-naphthalenesulfonic
      acid (ANS) bearing negative charge (SO(3)(-)) and moderate hydrophobicity depends
      on the magnitude of zeta-potential of the particles; viz., the particles with
      zeta-potential of 53.6 mV show the highest efficiency of uptake. The diameter and
      the beta-CD contents are closely related with the water/surfactant ratio, and the
      zeta-potentials are dependent on both the diameter and the beta-CD contents.
      Inclusion of ANS into the CD cavity of EGDGE/AEC-beta-CD particles can be
      controlled by electrostatic interaction between ANS (negatively charged) and the
      particle (positively charged). Namely, synergistic effect of cavity-inclusion and
      electrostatic interaction can dominate the uptake of guest molecules by the
      particles.

PMID- 16414221
TI  - In vitro permeation of repellent DEET and sunscreen oxybenzone across three
      artificial membranes.
AB  - DEET and oxybenzone are two essential active ingredients in repellent and
      sunscreen products. We performed a series of in vitro diffusion studies to
      evaluate the transmembrane permeation of DEET and oxybenzone across three
      artificial membranes, low-density polyethylene (LDPE), low fouling composite
      (LFC) and mixed cellulose esters (MCE), from concurrent use of commercial
      repellent and sunscreen preparations. Permeation of DEET and oxybenzone across
      the test membranes was synergistically increased when both the repellent and the
      sunscreen formulations were applied simultaneously. Different application
      sequences and formulation types also resulted in variable permeation profiles of
      DEET and oxybenzone. Compared to biological piglet epidermis under the identical
      experimental conditions, transmembrane permeation of DEET was suppressed in LDPE
      and LFC membranes, but enhanced in MCE membrane; transmembrane permeation of
      oxybenzone was reduced in LFC membrane, but increased in LDPE and MCE membranes.
      Permeability coefficients of DEET and oxybenzone in all three artificial
      membranes were significantly different from those in piglet skin. It was
      concluded that the permeation profiles of the compounds were dependent upon
      physicochemical characteristics of the membranes and the formulations.

PMID- 16414222
TI  - A new hydrogel for the extended and complete prednisolone release in the GI
      tract.
AB  - The issue of incomplete release of poorly soluble drugs from sustained-release
      oral formulations is addressed using prednisolone (PDS) as the model drug and a
      novel highly swelling hydrogel as the rate-controlling material. The hydrogel was
      formed by heating N-carboxymethylchitosan (CMC) to 80 degrees C for 24 h.
      Swelling, alkalimetry, FTIR, DSC, and solid-state NMR studies showed that the
      treatment produced physical crosslinking, i.e., polymer chain entanglement. A
      controlled-release system was prepared by coating an inert compacted support of
      ethylcellulose (50 mg; diameter, 6 mm) with a CMC layer containing dispersed PDS
      powder (10-50 microm). The system was heated to crosslink the CMC coating, then
      drug release to simulated GI fluids was studied in vitro. The drug release
      pattern and term were modulated via the layer mass (LM) (10 or 14 mg cm(-2))
      and/or the drug-polymer wt ratio (D/P) (1:5 or 2:5). The rate parameter, K, and
      the time exponent, n, of the Peppas equation were: K=26.6+/-0.3 h(-n), n = 0.78+/
      0.02 (LM, 10 mg cm(-2); D/P, 1:5); K = 24.7+/-0.7 h(-n), n = 0.56+/-0.02 (LM, 14
      mg cm(-2); D/P, 1:5); K = 20.7+/-0.3 h(-n), n = 0.76+/-0.01 (LM, 10 mg cm(-2);
      D/P, 2:5). Hydrogel swelling was faster than drug release. This was controlled,
      in a first stage, by drug dissolution-diffusion in the swollen gel, and
      subsequently, by diffusion. The drug release rate was unaffected by the GI pH
      variations, and slightly affected by the environmental hydrodynamics. The system
      promises an extended and complete release of poorly soluble drugs in the GI
      tract.

PMID- 16414223
TI  - Ethnopharmacological survey of plants used for the treatment of schistosomiasis
      in Niono District, Mali.
AB  - In Mali the use of traditional medicine is a wide spread phenomenon, not only
      because of its cultural importance, but also as the majority of people cannot
      afford the western drugs or medicines. In Mali, the Office du Niger area
      constitutes the main zone of schistosomiasis transmission where both Schistosoma
      mansoni and Schistosoma haematobium are encountered. An ethnopharmacological
      survey, using questionnaire, was conducted in the Office du Niger area of the
      Niono District to determine the plants used against schistosomiasis amongst
      traditional healers. Forty healers from 21 villages of six different health areas
      were interviewed. All interviewed healers knew about urinary schistosomiasis,
      while only six knew about the intestinal form. The presence of blood in urine was
      reported as the main symptom of urinary schistosomiasis. Fifty-five plants
      belonging to 30 families were reported to be used alone for treating urinary and
      intestinal schistosomiasis, while nine combinations of plants were used against
      the urinary form of the disease. Cissus quadrangularis and Stylosanthes erecta
      were the plants most frequently used and were reported for the first time, to be
      used against schistosomiasis in Mali.

PMID- 16414224
TI  - Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants.
AB  - Thirty samples of Indonesian medicinal plants were tested for their mechanism
      based inhibition on cytochrome P450 3A4 (CYP3A4) and CYP2D6 via erythromycin N
      demethylation and dextromethorphan O-demethylation activities in human liver
      microsomes. From screening with 0 and 20min preincubation at 0.5mg/ml of methanol
      extracts, five plants (Cinnamomum burmani bark, Foeniculum vulgare seed,
      Strychnos ligustrina wood, Tinospora crispa stem, and Zingiber cassumunar
      rhizome) showed more than 30% increase of CYP3A4 inhibition, while three (Alpinia
      galanga rhizome, Melaleuca leucadendron leaf, and Piper nigrum fruit) showed more
      than 30% increase of CYP2D6 inhibition. In these eight plants, Foeniculum vulgare
      seed, Cinnamomum burmani bark, and Strychnos ligustrina wood showed time
      dependent inhibition on CYP3A4 and Piper nigrum fruit and Melaleuca leucadendron
      leaf on CYP2D6. Among these, four plants other than Melaleuca leucadendron
      revealed NADPH-dependent inhibition. Thus, Foeniculum vulgare, Cinnamomum
      burmani, and Strychnos ligustrina should contain mechanism-based inhibitors on
      CYP3A4 and Piper nigrum contain that on CYP2D6.

PMID- 16414225
TI  - Traditional medicine in Central Sahara: pharmacopoeia of Tassili N'ajjer.
AB  - Further to the previously reported ethnobotanical surveys of North-Sahara and
      Ahaggar [Maiza, K., Brac de la Perriere, R.A., Bounaga, N., Hammiche, V., 1990.
      Usages traditionnels des plantes spontanees d'El Golea. Actes du Colloque de
      l'Association. Francaise pour la Conservation des Especes Vegetales, Mulhouse;
      Maiza, K., Hammiche, V, Bounaga, N., Brac de la Perriere, R.A., 1992. Inventaire
      des plantes medicinales de trois regions d'Algerie. Actes du Colloque
      International hommage a Jean Pernes: Complexes d'especes, flux de genes,
      ressources genetiques des plantes. Paris, pp. 631-633; Maiza, K., Brac de la
      Perriere, R.A., Hammiche, V., 1993a. Traditional Saharian pharmacopoeia. Acta
      Horticulturae, I.S.H.S. 332, 37-42; Maiza, K., Brac de la Perriere, R.A.,
      Hammiche, V., 1993b. Recents apports a l'ethnopharmacologie du Sahara algerien:
      Actes du 2eme Colloque Europeen d'Ethnopharmacologie & 11eme Conference
      Internationale d'Ethnomedecine. Heidelberg, pp. 169-171; Maiza, K., Brac de la
      Perriere, R.A., Hammiche, V., 1995. Pharmacopee traditionnelle saharienne. Revue
      de Medecines et Pharmacopees Africaines, 9 (No. 1), 71-75; Maiza, K., Smati, D.,
      Brac de la Perriere, R.A., et Hammiche, V., 2005. Pharmacopee traditionnelle au
      Sahara Central: Pharmacopee de l'Ahaggar. Retenu pour publication. Revue de
      Medecines et Pharmacopees Africaines.], we have now moved our investigations on
      Tassili N'Ajjer, another distinct region of the Southern Algerian Sahara.
      Ethnobotanic research has been carried out through interviews with nomad
      populations and the traditional pratictionners of recognised competence. To date,
      80 wild indigenous medicinal plants have been identified and are currently used
      by the local population for various illnesses. Information on their vernacular
      Tamahaq and Arabic names, their flowering distribution, the parts used, the modes
      of preparation and routes of administration are reported and discussed in this
      paper. This work completes our investigation in Central Sahara.

PMID- 16414226
TI  - Inhibition of trypsin-induced mast cell activation by acanthoic acid.
AB  - Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal
      plant, Acanthopanax koreanum (Araliaceae). In the present study, we examined
      whether AA has the inhibitory effect on the production of inflammatory mediators
      and activating signals induced in trypsin-treated human leukemic mast cell-1 (HMC
      1). HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence
      of AA (1, 10, and 100 microg/ml). We assessed the production of TNF-alpha and
      tryptase by enzyme-linked immunosorbent assay (ELISA) or reverse transcription
      PCR, ERK activation by Western blot, and NF-kappaB activation by gel shift assay.
      AA (10 and 100 microg/ml) significantly inhibited production of both TNF-alpha
      and tryptase in a dose-dependent manner in trypsin-stimulated HMC-1. Furthermore,
      AA inhibited ERK phosphorylation and NF-kappaB activation induced by trypsin
      treatment without blocking of trypsin activity even with 100 microg/ml. These
      results suggest that AA may inhibit the production of inflammatory mediators
      through inhibition of ERK phosphorylation and NF-kappaB activation pathway in
      human mast cells. It supports the evidence that AA may be used to blocks the
      development of inflammation caused from mast cells.

PMID- 16414228
TI  - Basal cell adenomas of the parotid gland: CT scan features.
AB  - Basal cell adenoma (BCA) is a rare tumor of the parotid gland, and except for a
      few case reports, the imaging features of this pathological entity are not well
      described. We describe the computed tomography (CT) features of 14 cases of
      histologically proven BCA, the largest series to date. In all cases, the tumor
      appeared as a round or oval, sharply marginated mass. Three cases showed
      homogenous enhancement. In the other 11 cases, the enhancement was inhomogeneous,
      due to either cystic areas, linear bands or stellate-shaped areas of non
      enhancement. The latter two patterns have not been previously described in BCA or
      other parotid tumors, and may therefore aid in distinguishing BCA from other
      benign parotid neoplasms on CT.

PMID- 16414227
TI  - Complex inheritance and parent-of-origin effect in juvenile myoclonic epilepsy.
AB  - BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized
      epilepsy (IGE) with complex inheritance. Previous studies have suggested maternal
      inheritance and female excess in IGEs but have not been specific for JME. We
      investigated evidence for maternal inheritance, female excess and patterns of
      familial seizure risk in a well-characterized sample of JME families. METHODS: We
      ascertained 89 families through a JME proband and 50 families through a non-JME
      IGE proband. JME families were divided into those with and without evidence of
      linkage to the EJM1 susceptibility locus on chromosome 6. We analyzed
      transmission in 43 multigenerational families, calculated the adjusted sex ratio
      for JME, and looked for evidence of seizure specific risk in 806 family members.
      RESULTS: We found evidence for preferential maternal transmission in both EJM1
      linked and unlinked families (2.7:1), evidence even more marked when potential
      selection factors were excluded. The adjusted female: male risk ratio was very
      high in JME (RR=12.5; 95% CI: 1.9-83.7). Absence seizures in JME probands
      increased the overall risk of seizures in first degree relatives (15.8% vs. 7.0%,
      P=0.011), as well as first-degree relatives' specific risk of absence seizures
      (6% vs. 1.6%, P=0.01), but not myoclonic seizures. CONCLUSIONS: We have confirmed
      the finding of maternal inheritance in JME, which is not restricted to JME
      families linked to the EJM1 locus. The striking female excess in JME may relate
      to anatomical and/or endocrine sexual dimorphism in the brain. Evidence for
      independent inheritance of absence and myoclonic seizures in JME families
      reinforces a model in which combinations of loci confer susceptibility to the
      component seizure types of IGE.

PMID- 16414229
TI  - Focal nodular hyperplasia.
AB  - Focal nodular hyperplasia is the second most common benign liver tumor after
      hemangioma and occurs predominantly in young women. Imaging techniques are
      crucial in the diagnosis of this lesion. In this article, we will present the
      imaging findings of the classic and non-classic FNHs. The role of percutaneous
      biopsy will also be detailed.

PMID- 16414230
TI  - Application of superparamagnetic iron oxide to imaging of hepatocellular
      carcinoma.
AB  - Superparamagnetic iron oxide (SPIO) particles are as MR contrast media composed
      of iron oxide crystals coated with dextran or carboxydextran. These particles are
      sequestered by phagocytic Kupffer cells in normal reticuloendothelial system
      (RES), but are not retained in tumor tissue. Consequently, there are significant
      differences in T2/T2* relaxation between normal RES tissue and tumors, which
      result in increased lesion conspicuity and detectability. The introduction of
      SPIO has been expected to substantially increase the detectability of hepatic
      metastases. For focal hepatocellular lesions, it has been documented that SPIO
      enhanced MR imaging exhibits slightly better diagnostic performance than dynamic
      helical CT in the detection of hypervascular hepatocellular carcinoma (HCC). A
      combination of dynamic and static MR imaging technique using T1- and T2 imaging
      criteria appears to provide clinically more useful patterns of enhancement. SPIO
      enhanced MR imaging also provides information useful for differential diagnosis,
      via enhancement of RES-containing tumors. With the exploitation of rapid T2*
      sensitive sequences, SPIO-enhanced dynamic MR imaging may become comparable to
      gadolinium-enhanced dynamic MR imaging and dynamic studies with multidetector-row
      CT. SPIO-enhanced MR imaging plays an important role in therapeutic decision
      making for patients with HCC.

PMID- 16414231
TI  - Application and validation of chemometrics-assisted spectrophotometry and liquid
      chromatography for the simultaneous determination of six-component
      pharmaceuticals.
AB  - Three methods are developed for the simultaneous determination of theophylline
      anhydrous (TH), guaiphenesin (GP), diphenhydramine hydrochloride (DP),
      methylparaben (MP), propylparaben (PP) and sodium benzoate (BZ) in pharmaceutical
      syrup. The chromatographic method depends on a high performance liquid
      chromatographic separation on a reversed-phase C(18) column at ambient
      temperature with mobile phase consisting of 25 mM KH2PO4, pH 3.2-acetonitrile
      (60:40, v/v). Quantitation was achieved with UV detection at 222 nm based on peak
      area. The other two chemometric methods applied were partial least squares (PLS
      1) and principal component regression (PCR). These approaches were successfully
      applied to quantify the six components in the studied mixture using information
      included in the UV absorption spectra of appropriate solutions in the wavelength
      range of 220-270 nm with Deltalambda=0.4 nm. The calibration PLS-1 and PCR models
      were evaluated by internal validation (prediction of compounds in its own
      designed training set of calibration), by cross-validation (obtaining statistical
      parameters that show the efficiency for a calibration fit model) and by external
      validation over synthetic and pharmaceutical preparation. The results of PLS-1
      and PCR methods were compared with the HPLC method and a good agreement was
      found.

PMID- 16414233
TI  - Adjuvant therapy for patients with stage I papillary serous endometrial cancer.
AB  - Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial
      cancer characterized by a high recurrence rate and poor prognosis. Several
      studies have demonstrated that UPSC has a tendency to manifest with extra-uterine
      disease, even for tumors which appear to be limited to the endometrium. The data
      on adjuvant chemotherapy for stage I UPSC are limited, and the available studies
      are generally under-powered to assess if chemotherapy improves survival. However,
      we believe that, patients with UPSC should receive complete surgical staging,
      including omentectomy and peritoneal biopsies, and then until the results of
      larger series or randomized controlled trials will be available, we feel that
      combined radiotherapy and chemotherapy is justified for all stage I UPSC.

PMID- 16414232
TI  - Determination of vincristine in infant plasma by liquid chromatography
      atmospheric pressure chemical ionization-mass spectroscopy.
AB  - An LC-MS method using APCI has been developed and validated for the determination
      of the anticancer drug vincristine in human plasma, using vinblastine as internal
      standard. Following solid-phase extraction (SPE) of the sample, the lower limit
      of quantitation (LLOQ) was 0.18 ng/ml, the lower limit of detection was 0.09
      ng/ml, and the linear calibration range was 0.18-180 ng/ml. This method has been
      used to measure plasma concentrations of vincristine from 0.08 to 24 h post bolus
      in 29 infants as part of a pharmacokinetic study. Concentrations of vincristine
      at 24 h were 0.2-1.36 ng/ml.

PMID- 16414234
TI  - Outcome following lung resections for pT1 non-small cell lung cancer.
AB  - AIMS: To analyse the outcome of patients with pT1 NSCLC treated at our
      institution by antero-lateral thoracotomy, anatomical lung resections and
      mediastinal lymph node dissection between 1980 and 2001. METHODS: Follow-up data
      were obtained retrospectively from 1980 to 1990 and prospectively after 1990.
      Survival was analysed using the Kaplan-Meier method. RESULTS: Histopathological
      examinations revealed mediastinal lymph node infiltration in 27.6% (pN1 17.8% and
      pN2 9.8%). pN2 was classified in 14.1% of adenocarcinomas compared to 6.2% of
      squamous cell carcinomas. Median overall survival of patients with pT1 carcinomas
      was 89+16 months (median+standard error). Histopathological N-classification
      indicates differential prognostic and therapeutic implications in pT1 adeno- and
      squamous cell carcinomas. CONCLUSIONS: Complete lymph node dissection is required
      for all patients with T1 NSCLC treated by either open surgery or VATS resection.
      Histopathological N-classification indicates differential prognostic and
      therapeutic implications in pT1 adeno- and squamous cell carcinomas.

PMID- 16414235
TI  - Multicenter phase-I/II study using a combination of gemcitabine and docetaxel in
      metastasized and unresectable, locally advanced pancreatic carcinoma.
AB  - AIMS: To assess the maximum tolerability of a combined therapy regimen of
      gemcitabine and docetaxel, and to evaluate tumour response rate, survival time
      and tolerability in patients receiving these agents for advanced pancreatic
      carcinoma. PATIENTS AND METHODS: Patients (n=68) with pancreatic carcinoma
      (advanced and/or unresectable tumour growth or histopathologically diagnosed
      metastases) were enrolled in a multicenter phase-I (n=25) and phase-II study
      (n=43). Treatment during phase II of the study was continued until either
      complete tumour remission (CR), tumour progression, indicated clinically or by
      means of radiological imaging, or until unacceptable toxicity occurred. RESULTS:
      Phase I: the tolerability maximum of the combined agents was established at
      gemcitabine 1000 mg/m(2) and docetaxel 35 mg/m(2) with tolerable adverse events.
      Phase II: a total of 139 chemotherapy cycles were completed (mean, 3.2; range, 1
      10). While CR was achieved in three of 43 patients (7%), in five further cases,
      partial remission (PR) was documented, amounting to an overall response rate (OR)
      of 18.6%. Eighteen patients showed stable disease (41.9%), whereas in 17 of 43
      subjects (39.5%), primary tumour progression was detected. The median survival
      time was 9.0 months; the 1-year survival rate was 13.9% (six of 43 patients).
      These results were associated with a side-effect profile of moderate severity and
      acceptable quality of life (QOL). CONCLUSION: The combination of gemcitabine and
      docetaxel for chemotherapy in unresectable pancreatic carcinoma was well
      tolerated. Survival time and 1-year survival rate proved promising and the
      regimen appears suitable for further evaluation in a prospective phase-III study
      setting.

PMID- 16414236
TI  - An audit of surgical management of gastrointestinal stromal tumours (GIST).
AB  - AIM: To analyze GIST outcome after primary resection and to determine if a new
      grading system could adequately predict there prognosis. METHODS: A retrospective
      review (1993-2002) identified 80 patients who underwent primary surgical
      resection for, c-KIT positive, GIST. Follow-up was complete for all patients
      (median follow-up 42, range 1-132, months). GIST were classified as low or high
      grade according to the following parameters: size, mitotic rate, mitotic index
      (MiB1), presence of necrosis, invasion of adjacent structure and presence of
      metastasis. RESULTS: GIST originated from the stomach (46), small bowel (30),
      colon and rectum two and mesentery two. At surgery, 94% of cases presented with
      localized disease and 6% blood born metastasis with or without lymph node
      invasion. Resections were complete (R0) in 72 cases. R0 resection correlated with
      prognosis (p<0.01). Sixty GIST were classified as low grade (median follow-up 60
      months) and 20 as high grade (median follow-up 27 months). Five-year actuarial
      survival of patients with low or high grade GIST were of 95 and 21%,
      respectively, (p<0.001). CONCLUSION: Prognosis of GIST after surgical treatment
      is influenced by completeness of primary resection and tumour malignant
      potential. Low grade GIST have an excellent prognosis after surgery alone, while
      high grade GIST have a high rate of recurrence after primary resection. Adjuvant
      treatment should be advocated for patient with either high grade GIST or after
      incomplete primary resection. The presented grading system can reliably predict
      GIST outcome after primary surgical treatment. Complete surgical resection offers
      good chance of cure for low grade GIST, while for high grade GIST surgery alone
      is not sufficient. The presented grading system could be used to identify
      patients who may benefit of adjuvant treatment with imatinib mesylate after GIST
      resection.

PMID- 16414237
TI  - [Central venous lines in children: new trends].
AB  - Central venous catheterisation under two-dimensional ultrasound (US) guidance has
      been proved to be quicker and safer than the classical landmark method in both
      adults and children. In the literature US guidance with sterile dressing of the
      probe is the 'gold-standard'. Another way to use US is simple preoperative US
      location followed either by blind puncture, either by US guided puncture when
      difficulties are expected: small infants (<15 kg), small diameter or collapses of
      the vein, multiple unsuccessful attempts during blind technique. Ideal location
      of the tip of central venous catheters is no more controversial but can depend on
      age and weight. In 2002 a French agency (Afssaps) study showed that the risk of
      perforation and tamponade was especially high in small weight prematures with 27
      gauge polyurethane catheters when tip was located in the cardiac cavities. In
      children and adults venous thrombosis and catheter malfunction are closely
      related to short catheters whose tip is above T3-T4. Excepted polyurethane
      catheters in small weight prematures, the best location of long-term central
      venous catheters tip is the superior vena cava-right auricle junction. At this
      time routine antithrombotic prophylaxis is not recommended for children with long
      term central venous catheters.

PMID- 16414238
TI  - [Lumbodynia and coma].

PMID- 16414239
TI  - [The national STRATAGEM study: the success needs everyone's contribution!].

PMID- 16414240
TI  - [Shoulder dislocation after cardioversion].

PMID- 16414241
TI  - Characterization of leukotoxin from a clinical strain of Actinobacillus
      actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans is a Gram negative pathogen that is the
      etiologic agent of localized aggressive periodontitis (LAP), a rapidly
      progressing and severe disease of the oral cavity that affects predominantly
      adolescents. A. actinomycetemcomitans is also found in extraoral infections
      including infective endocarditis. As one of its many virulence determinants, A.
      actinomycetemcomitans produces the RTX (repeats in toxin) exotoxin, leukotoxin
      (LtxA). LtxA specifically kills leukocytes of humans and Old World Monkeys. All
      of our current knowledge of A. actinomycetemcomitans LtxA is based on the protein
      from strain JP2, a nonadherent laboratory isolate. Because laboratory isolates
      can lose virulence properties, we wished to examine LtxA from a clinical isolate,
      NJ4500. We show that localization patterns of LtxA do not differ between the
      strains. Subcellular localization studies with NJ4500 revealed that LtxA
      localizes to the outer membrane and that the interaction between LtxA and the
      surface of cells is specific. Surface localized LtxA was not removed with NaCl
      treatment and protease protection experiments revealed that approximately 10 kDa
      of LtxA is exposed. We purified secreted LtxA from NJ4500 and found that the
      specific activity of this toxin was greater than that of secreted LtxA from JP2.
      For other RTX toxins, fatty acid modification affects toxin activity, and A.
      actinomycetemcomitans LtxA is predicted to be modified. We show by two
      dimensional gel electrophoresis that NJ4500 LtxA is more highly modified than JP2
      LtxA, suggesting that the difference in activities could be due to differential
      modification. Studies of A. actinomycetemcomitans pathogenesis should therefore
      consider LtxA from clinical isolates.

PMID- 16414242
TI  - Inhalational model of cocaine exposure in mice: neuroteratological effects.
AB  - We developed a novel inhalation-based mouse model of prenatal cocaine exposure.
      This model approximates cocaine abuse via smoking, the preferred route of cocaine
      administration by heavy drug users. The model is also characterized by (i)
      absence of procedural stress from drug administration, (ii) long-term drug
      exposure starting weeks before pregnancy and continuing throughout the entire
      gestation, and (iii) self-administration of cocaine in multi-hour daily sessions
      reminiscent of drug binges, which allows animals to set up the levels of their
      own drug consumption. The offspring of female mice inhaling cocaine in our model
      displayed no gross alterations in their cortical cytoarchitecture. These
      offspring, however, showed significant impairments in sustained attention and
      spatial working memory. We hope that the introduction of the present model will
      lead to a significant increase in our understanding of outcomes of prenatal
      cocaine exposure.

PMID- 16414243
TI  - Evaluation of cognitive function in weanling rats: a review of methods suitable
      for chemical screening.
AB  - Current developmental neurotoxicity (DNT) tests that are used for environmental
      agents require cognitive testing around the age of weaning as well as adulthood.
      There are challenges associated with testing weanling rodents that are not
      present with testing older subjects, including rapid brain development, and the
      impact of food or water restriction necessary for appetitive paradigms. This
      review provides an overview of cognitive tests that can be used for laboratory
      rodents in the context of such DNT studies; as such, those requiring surgery or
      food/water deprivation are excluded. Potential test methods described herein
      include spontaneous, avoidance, conditioned, spatial, and sequential behavioral
      assays; although, some procedures meet scientific and regulatory requirements
      better than others. Scientific judgment should be exercised in the choice of
      cognitive measures for weanling rodents in DNT studies, and should include an
      assessment of the sensitivity and efficiency of the procedure, an understanding
      of the literature and the neuronal substrates involved, and evaluation of
      available information on the mode(s) of action of the test chemical.

PMID- 16414244
TI  - Lateral femoral cutaneous nerve and iliac crest bone grafts--anatomical and
      clinical considerations.
AB  - This study investigates the topographical relationship of the lateral femoral
      cutaneous nerve (LFCN) to the anterior iliac crest and its clinical relevance in
      the context of bone graft harvesting. In the anatomical part of the study, LFCN
      was dissected and its course investigated in 34 human formalin-embalmed cadavers.
      In the clinical part, data of patients who underwent an iliac crest bone grafting
      procedure were collected and analysed. The obtained results were then compared
      with the results of other investigators published in the medical literature. From
      34 nerves, the lateral branch of 1 LFCN (2.9%) crossed the anterosuperior iliac
      spine (ASIS) prominence at a distance less than 5mm superolaterally from the most
      anterior point of the spine. All other nerves ran below the inguinal ligament
      with an average distance of 14.6mm in the inferomedial direction from the spine.
      In 4 out of 298 patients (1.3%) who underwent harvesting of monocortical bone
      grafts from the inner table of the ilium, sensory disturbances in the dermatome
      of LFCN were observed. After a maximum period of 12 months all sensory
      disturbances resolved so that no case of permanent sensory impairment was
      recorded. The relatively low incidences of iatrogenic LFCN damage can be
      attributed to a standardized surgical concept which employs a lateral incision
      and layer by layer dissection to the periosteum/iliacal fascia level in order to
      identify the nerves potentially crossing the iliac crest above the ASIS.

PMID- 16414245
TI  - Preliminary investigation of gene expression profiles in peripheral blood
      lymphocytes in schizophrenia.
AB  - Schizophrenia is a heterogenous disorder that is phenomenologically characterised
      by a combination of negative, positive, and cognitive symptoms with variable
      expression in the course of illness. Here, we investigated differential gene
      expression in relation to age to address the heterogeneity of this disorder We
      used 6000 gene cDNA microarrays to generate gene expression profiles from
      peripheral blood lymphocytes from 14 individuals with schizophrenia and 14 non
      psychiatric controls. Genes showing altered expression were identified and 18
      genes with brain-related functions were altered, 4 of which, endothelial
      differentiation gene 2 (Edg-2), ezrin-radixin-moesin phosphoprotein 50 (EBP50),
      Myc-associated zinc finger protein (MAZ) and Tumor Necrosis Factor Receptor 2
      (TNFR2), were confirmed by relative real-time PCR. Dendrograms were constructed
      using genes that showed significantly different expression (p<0.05) between
      groups based on median split of age dividing the matched pairs into distinct
      subclasses. Our findings suggest that distinct gene expression profiles in
      peripheral blood lymphocytes associated with schizophrenia phenotypes may provide
      a first step towards the biological classification of schizophrenia subtypes. The
      validity of this approach may lead to better methods of defining this enigmatic
      disease.

PMID- 16414246
TI  - Genotype analysis of Candida albicans isolates obtained from different body
      locations of patients with superficial candidiasis using PCRs targeting 25S rDNA
      and ALT repeat sequences of the RPS.
AB  - BACKGROUND: Several molecular biology-based genotyping techniques have been
      adapted for studying the molecular characteristics of Candida albicans strains,
      which constitute the majority of the etiologic agents in candidiasis. Recently,
      we reported a PCR system targeting 25S rDNA and ALT repeat sequences in the
      repetitive sequence (RPS) for genotyping of C. albicans. OBJECTIVE: To assess the
      potential of 25S rDNA and RPS-based genotyping for studying the molecular
      epidemiology of C. albicans, and define the genotypic relationship of C. albicans
      between invasive and non-invasive lesions in the same individual. METHODS: C.
      albicans strains were isolated from infected lesions and commensal sites, such as
      oral mucosa and/or feces, of patients with superficial candidiasis. The genomic
      DNAs were amplified by PCRs using P-I and P-II to determine the 25S rDNA- and RPS
      based genotypes of the isolates. RESULTS: Genotype A:3 C. albicans constituted
      the majority of the isolates, followed by A:3/4 and B:3 C. albicans. There was
      usually one genotype of C. albicans per person. The genotypes of infected lesion
      isolates and non-infected oral mucosa and/or feces isolates were identical in the
      same individual, even in serially isolated C. albicans. CONCLUSION: The results
      indicate that our combined PCR technique using P-I and P-II is a potential tool
      for molecular typing of C. albicans, and reveal that the genotypes of isolates
      are identical in the same individual, independent of the infective and non
      infective phases or the body location.

PMID- 16414247
TI  - In vitro interactions of anidulafungin with azole antifungals, amphotericin B and
      5-fluorocytosine against Candida species.
AB  - Anidulafungin, an echinocandin, is in late stage development for the treatment of
      fungal infections. We investigated the activity of anidulafungin in combination
      with other antifungal agents (fluconazole, itraconazole, ketoconazole,
      amphotericin B and 5-fluorocytosine) against four isolates each of Candida
      albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis, and two
      isolates of Candida krusei using a macrobroth chequerboard method with
      interactions evaluated by fractional inhibitory concentration indices (FICIs).
      Additive activity (FICI > 0.5 to 1) or indifference (FICI > 1 to < 4) was
      observed in 85 of 90 interactions of anidulafungin with another antifungal agent.
      Synergy with itraconazole (FICI<or=0.5) was observed for one strain of C.
      glabrata, and antagonism with ketoconazole (FICI>or=4), a drug rarely used
      systemically, was noted for four strains of C. tropicalis. The combination of
      anidulafungin and amphotericin B demonstrated additive activity for each of the
      18 isolates of Candida tested. These results suggest additional studies are
      warranted, for example in animal models, to evaluate further the potential of
      combination antifungal therapy with anidulafungin for Candida infections.

PMID- 16414248
TI  - Trough serum concentrations of beta-lactam antibiotics in cancer patients:
      inappropriateness of conventional schedules to pharmacokinetic/pharmacodynamic
      properties of beta-lactams.
AB  - Serum concentrations of beta-lactams that continuously exceed the minimum
      inhibitory concentration may improve therapeutic outcomes for immunosuppressed
      patients. The trough serum levels of ceftazidime (CAZ), cefepime (FEP) or
      imipenem (IMP) were prospectively determined on days 1 and 3 of treatment in
      cancer patients. Seventy-eight episodes of suspected infection were analysed.
      Trough serum levels were higher than 4 mg/L in 62%, 24% and 0% of cases in the
      CAZ, FEP and IMP groups, respectively, and were higher than 20 mg/L in 24% of
      cases in the CAZ group compared with 0% both in the FEP and IMP groups. For
      suspected infectious episodes in cancer patients, the traditional intermittent
      regimen of beta-lactams does not appear to be appropriate for the
      pharmacokinetic/pharmacodynamic properties of these antibiotics.

PMID- 16414249
TI  - Antipsychotic type and correlates of antipsychotic treatment discontinuation in
      the outpatient treatment of schizophrenia.
AB  - Antipsychotic medication maintenance and the factors influencing it were analyzed
      using data from the SOHO study, a large observational study of the outcomes of
      antipsychotic treatment for schizophrenia in Europe. A total of 7186 adult
      patients in the outpatient setting who were initiating or changing their
      antipsychotic medication and who were prescribed only one antipsychotic after the
      baseline visit were analyzed. Medication maintenance at 12 months varied with the
      type of antipsychotic prescribed, being highest with clozapine (79.5%) and
      olanzapine (77.0%), and lowest with quetiapine (51.4%) and amisulpride (58.2%).
      Multiple logistic regression analysis demonstrated that the type of antipsychotic
      prescribed at baseline was the most important predictor of medication
      maintenance. Alcohol dependency, taking mood stabilizers, compulsory admission or
      arrest in the previous 6 months, greater clinical severity, and changing
      antipsychotic medication due to lack of effectiveness at baseline predicted a
      higher frequency of medication discontinuation in the subsequent 12 months. In
      contrast, medication maintenance was higher among patients who were treatment
      naive at baseline, socially active or who had loss of libido at baseline. The
      findings from this study should be interpreted conservatively because of its non
      randomized observational design.

PMID- 16414250
TI  - Risperidone in the management of agitation and aggression associated with
      psychiatric disorders.
AB  - OBJECTIVE: This review provides an overview of the prevalence and treatment of
      agitation and aggression, and focuses on the use of risperidone to treat these
      symptoms in patients from different age groups. METHODS: MEDLINE and EMBASE
      databases were used to identify controlled studies of risperidone in the
      treatment of disruptive behavior disorders and pervasive developmental disorders
      in pediatric patients, acute agitation or aggression in adults, and psychological
      and behavioral symptoms of dementia in the elderly. Additionally, key open-label,
      long-term trials assessing the efficacy and safety of risperidone were
      considered. RESULTS: The results of the 19 double-blind studies identified showed
      that risperidone is effective in treating agitation and aggression in the
      different populations, regardless of age. The safety and tolerability of
      risperidone appear to be good overall but certain safety issues, such as a higher
      risk of cerebrovascular adverse events in the elderly with dementia, were
      highlighted. CONCLUSIONS: Risperidone is useful for treating aggression and
      agitation associated with various psychiatric disorders in patients from
      different age groups.

PMID- 16414251
TI  - Is there an association between the COMT gene and P300 endophenotypes?
AB  - P300 wave anomalies correlate with genetic risk for schizophrenia and constitute
      a plausible endophenotype for the disease. The COMT gene is thought to influence
      cognitive performance and to be a susceptibility gene for schizophrenia. Unlike
      two previous studies, we found no significant influence of the COMT gene on P300
      amplitude or latency in 189 individuals examined. The well-supported role of the
      COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a
      strong theoretical case for the influence of COMT Val158Met polymorphism on P300
      endophenotypes. However, the available neurophysiologic evidence suggests that
      any such association, if present, must be very subtle.

PMID- 16414252
TI  - Imaging and manipulation of adsorbed lipid vesicles by an AFM tip: experiment and
      Monte Carlo simulations.
AB  - Single lipid vesicles adsorbed on SiO(2) were manipulated using an atomic force
      microscope (AFM) operated in contact mode. For large force setpoints, single
      vesicles were either pushed sideways or ruptured by the tip, depending on the tip
      type (sharp or blunt) used, while for small force setpoints the vesicles were
      imaged by the tip. To extend the interpretation of and to guide the experiment,
      we have developed a generic model of the vesicle-tip-substrate system and
      performed Monte Carlo simulations, addressing the influence of force setpoint and
      tip speed and shape on the type of imaging or manipulation observed.
      Specifically, we have explored AFM-image height and width variations versus force
      setpoint, typical AFM images for small and large force setpoints, tip-induced
      vesicle strain versus force setpoint, typical vesicle shapes during pushing for
      different tip speeds, and the details of vesicle rupture induced by the tip.

PMID- 16414253
TI  - Effect of granulocyte macrophage-colony stimulating factor (GM-CSF) on 5-FU
      induced ulcerative mucositis in hamster buccal pouches.
AB  - The present study was performed to investigate the protective effects of
      granulocyte macrophage-colony stimulating factor (GM-CSF) against ulcerative
      mucositis in hamster buccal pouch. GM-CSF was topically administered to the
      buccal pouches of hamsters with two different doses of 5 and 20 microg/ml. The
      treatment of GM-CSF led to rapid healing effects in gross and histopathological
      findings. It decreased expression of pro-inflammatory cytokine mRNA levels in the
      mucosal tissue of buccal pouches. Also GM-CSF-treated animals showed high numbers
      of Ki-67 positive cells in basal cell layer. These results suggest that GM-CSF
      provided excellent healing effects to ulcerative mucositis in the buccal pouch of
      hamster.

PMID- 16414254
TI  - Three-dimensional analysis of isolated hexosaminidase-altered aberrant crypts
      from colons of 1,2-dimethylhydrazine-treated rats.
AB  - Aberrant crypt foci, consisting of morphologically irregular crypts, are thought
      to be precancerous lesions for colorectal cancers. For analysis of individual
      crypts, F344 rats were administered weekly subcutaneous injections of 1,2
      dimethylhydrazine ten times and sacrificed at experimental weeks 10 and 20 with 5
      bromo-2'-deoxyuridine (BrdU) incorporation 1 h before the sacrifice. Isolated
      colonic crypts were classified into hexosaminidase-altered aberrant crypts
      (HAACs) and hexosaminidase-preserved normal-appearing crypts (HPNCs) and
      stereopaired images (tilt angle, 6 degrees ) were taken with a scanning electron
      microscope for three-dimensional analyses. While HPNCs showed symmetrical fission
      at the base, HAACs exhibited abnormal budding in the middle of the crypt body. At
      week 10, average BrdU labeled cells per crypt for DMH-treated HPNCs and HAACs
      were 4.9 +/- 1.0 and 18.7 +/- 2.2 (P < 0.0001), respectively, while the value for
      non-treated control crypts was 14.7 +/- 0.8/crypt. BrdU-positive cell numbers per
      unit crypt length (100 microm) in HPNCs and HAACs were 1.75 +/- 0.37 and 5.99 +/-
      0.70 (P < 0.0001), respectively, while that for the control was 6.65 +/- 0.35 (P
      < 0.02 vs. HAAC). At the 20-week time point, the numbers per crypt were 4.0 +/-
      0.8, 10.1 +/- 1.6, and 27.4 +/- 2.4, respectively, the control value being
      significantly higher than the others (P < 0.0001). The figures per unit length
      were 1.72 +/- 0.35, 2.92 +/- 0.42, and 13.39 +/- 1.11 (P < 0.0001 vs. HAAC and
      HPNC), respectively. BrdU incorporating cells were distributed in the bottom
      third of the crypt columns in HAACs, but only 18% in the HPNCs, providing
      evidence of hyperplasia. HAACs could be good surrogate indicators of carcinogen
      exposure, at least some of which may be related to colon carcinogenesis.

PMID- 16414256
TI  - Innovative analytical system for screening on lectins.
AB  - Lectins are proteins or glycoproteins from plants, animals or microorganisms,
      which typically bind specifically to sugar residues, e.g., those located in cell
      walls or membranes. This reaction might change the physiology of the cell wall
      and influences the metabolism inside the cell. Some lectins of plants stimulate
      the immune system by unspecific activation of T-cells or influence cell division;
      others cause agglutination of cells (e.g., erythrocytes) and are therefore from
      therapeutic interest. In a new approach, biomolecular interaction analysis (BIA)
      was utilized for a screening program on lectins. The BIA has been done by a new
      interferometric biosensor based on spectral-phase interference (SPI). The system
      can be used either for characterisation of lectin binding domains or for a
      screening on lectins obtained from natural sources. Several lectin binding
      surfaces on the basis of SPI have been established.

PMID- 16414255
TI  - Crosslinking of phenylboronic acid receptors as a means of glucose selective
      holographic detection.
AB  - A holographic sensor for the detection of glucose has been developed that is
      based on a hydrogel film containing phenylboronic acid receptors. Changes to the
      replay wavelength of the hologram were used to characterise the swelling and de
      swelling behaviour of the hydrogel matrix upon receptor-ligand binding. The
      effect of introducing a fixed positive charge into the polymer matrix by
      modification of the hydrogel with a quaternary amine group (3
      acrylamidopropyl)trimethylammonium chloride (ATMA), was investigated for a range
      of sugars and the alpha-hydroxy acid, lactate, at physiological pH. The
      quaternary amine-modified hydrogel matrix was found to contract in the presence
      of glucose, whereas, it was minimally responsive to other saccharides. The
      selectivity of the sensor for glucose compared to lactate was also significantly
      improved compared to the unmodified film. A crosslinking mechanism is proposed to
      explain the enhanced selectivity to glucose.

PMID- 16414258
TI  - Dinitrophenyl ligand substrates and their application to immunosensors.
AB  - We present an approach for the development of highly specific and sensitive
      antibody based biosensors by chemically tailoring the sensor surface with
      materials that control specific and nonspecific binding of biologically relevant
      molecules. As a model system we employed surface immobilized 2,4-dinitrophenyl
      (DNP)-ligands that bind specifically to anti-DNP antibodies. Self-assembling
      characteristics and minimization of the nonspecific interactions were used in the
      ligand design. The redox activity of the DNP-head group was used to calculate the
      surface density (coverage) of these assemblies using cyclic voltammetry. Quartz
      crystal microbalance (QCM) and impedance analysis were used to assess the ligand
      antibody interaction and estimate the quantity of antibodies bound to the
      surface. The ligand surface density and the QCM data were useful in determining
      the sensitivity of our model system. A simple two-step kinetic model was shown to
      fit the experimental data.

PMID- 16414257
TI  - Surface-enhanced resonance Raman spectroscopy and spectroscopy study of redox
      induced conformational equilibrium of cytochrome c adsorbed on DNA-modified metal
      electrode.
AB  - The redox-induced conformational equilibrium of cytochrome c (cyt c) adsorbed on
      DNA-modified metal electrode and the interaction mechanism of DNA with cyt c have
      been studied by electrochemical, spectroscopic and spectroelectrochemical
      techniques. The results indicate that the external electric field induces
      potential-dependent coordination equilibrium of the adsorbed cyt c between its
      oxidized state (with native six-coordinate low-spin and non-native five
      coordinate high-spin heme configuration) and its reduced state (with native six
      coordinate low-spin heme configuration) on DNA-modified metal electrode. The
      strong interactions between DNA and cyt c induce the self-aggregation of cyt c
      adsorbed on DNA. The orientational distribution of cyt c adsorbed on DNA-modified
      metal electrode is potential-dependent, which results in the deviation from an
      ideal Nernstian behavior of the adsorbed cyt c at high electrode potentials. The
      electric-field-induced increase in the activation barrier of proton-transfer
      steps attributed to the rearrangement of the hydrogen bond network and the self
      aggregation of cyt c upon adsorption on DNA-modified electrode strongly decrease
      the interfacial electron transfer rate. In addition, the strongly Coulombic
      interactions between DNA and cyt c only disturb the microenvironment of the heme,
      and do not affect the states of heme ligation and spin. The secondary structure
      of the adsorbed cyt c is retained, while the conformation of DNA is changed from
      the B form DNA to A form DNA.

PMID- 16414259
TI  - Phosphorylation of tyrosine 1248-ERBB2 measured by chemiluminescence-linked
      immunoassay is an independent predictor of poor prognosis in primary breast
      cancer patients.
AB  - ERBB2 (HER2/Neu) gene amplification and overexpression is associated with
      increased risk of metastases and shorter survival in breast cancer. Tyrosine 1248
      is a major phosphorylation site of ERBB2 and reflects the activation status of
      the receptor. The aim of this study was to investigate the relationships between
      quantitative levels of pY1248-ERBB2 (p-ERBB2) and the expression of epidermal
      growth factor receptor (EGFR)-family members, and whether p-ERBB2 could provide
      additional prognostic value compared with established prognostic markers. For
      this purpose we developed a highly sensitive chemiluminescence-linked immunoassay
      (CLISA) and detected p-ERBB2 levels in 70 primary breast cancer biopsies.
      Phosphorylated ERBB2 correlated with EGFR and ERBB2, and inversely with oestrogen
      receptor (ER), progesterone receptor (PgR) and ERBB4 expression levels.
      Additionally, p-ERBB2 was associated with poor clinical outcome in univariate and
      multivariate Cox regression analysis. Further studies are needed to evaluate the
      predictive value of p-ERBB2.

PMID- 16414260
TI  - Surgical treatment of ovarian cancer in different hospital categories--a
      prospective nation-wide study in Finland.
AB  - This prospective nation-wide study was performed to evaluate the effect of
      hospital category and subspeciality training on surgical treatment of ovarian
      cancer. Data were obtained from a questionnaire filled in by the operating unit,
      and from the surgical and histopathology reports. The survey included 307
      patients. Half of them were operated in the university hospitals where
      gynaecologic oncologists performed 72% of the operations. This was the case in
      only 4% and 19% in the central and district hospitals, respectively. In
      university hospitals, pelvic lymphadenectomy was performed in 88%, and para
      aortic lymphadenectomy in 73%, of the patients with stage I disease. The
      corresponding figures ranged from 11% to 21% in central and district hospitals.
      For stage III patients operated by gynaecologic oncologists, the estimated odds
      ratio for no macroscopic tumour was 3.0 times higher (95% CI 1.2-7.5) than for
      those operated by general gynaecologists. These results favour centralisation of
      surgical treatment of ovarian cancer.

PMID- 16414261
TI  - Activation of membrane estrogen receptors induce pro-survival kinases.
AB  - Experimental and epidemiological data suggest a neuroprotective role for estrogen
      (E(2)). We have recently shown that, in PC12 cells, non-permeable estradiol
      conjugated to bovine serum albumin (BSA) prevent serum-deprivation induced
      apoptosis through activation of specific membrane estrogen receptors (mER). In
      the present study, we explored in detail the early signaling events involved in
      this anti-apoptotic action, downstream to activation of mER. Our findings suggest
      that mER is associated to G-proteins, and its activation with non-permeable E(2)
      BSA results in the activation of the following downstream pro-survival kinases
      pathways: (1) the PKB/Akt pathway, (2) the Src-->MEK-->ERK kinases and finally
      (3) the MAPK-->ERK kinases. Activation of these pro-survival signals leads to
      CREB phosphorylation and NFkappaB nuclear translocation, two transcription
      factors controlling the expression of anti-apoptotic Bcl-2 proteins. These data
      suggest that major pro-survival kinases are involved in the mER-mediated anti
      apoptotic effects of estrogen. This is further supported by experiments with
      specific kinases inhibitors, which partially but significantly reversed the mER
      mediated anti-apoptotic effect of E(2)-BSA. Our findings suggest that estrogen
      act via mER as potent cytoprotective factors, downstream activating pro-survival
      kinases, assuring thus an efficient and multipotent activation of the anti
      apoptotic machinery.

PMID- 16414262
TI  - Original investigation correlated joint fluctuations can influence the selection
      of steady state gait patterns in the elderly.
AB  - This investigation utilized a Markov model to investigate the relationship of
      correlated lower extremity joint fluctuations and the selection of a steady state
      gait pattern in the young and elderly. Our model simulated the neuromuscular
      system by predicting the behavior of the joints for the next gait cycle based on
      the behavior exhibited in the preceding gait cycles. Such dependencies in the
      joint fluctuations have been noted previously in the literature. We speculated
      that compared to the young model, the characteristics of the correlated
      fluctuations in the elderly model would result in the selection of a different
      steady state gait pattern. The results of our simulation support the notion that
      correlated fluctuations in the joint kinematics influence the selection of a
      steady state gait pattern. The steady state gait pattern for the elderly model
      was dependent the ankle and hip. Conversely, the steady state gait pattern for
      the young control model was dependent on the behavior of the knee and hip. Based
      on our model, we suggested that the altered steady state gait patterns observed
      in the elderly may be due to an altered neuromuscular memory of prior joint
      behaviors.

PMID- 16414263
TI  - Ground reaction force and 3D biomechanical characteristics of walking in short
      leg walkers.
AB  - Short-leg walking boots offer several advantages over traditional casts. However,
      their effects on ground reaction forces (GRF) and three-dimensional (3D)
      biomechanics are not fully understood. The purpose of the study was to examine 3D
      lower extremity kinematics and joint dynamics during walking in two different
      short-leg walking boots. Eleven (five females and six males) healthy subjects
      performed five level walking trials in each of three conditions: two testing boot
      conditions, Gait Walker (DeRoyal Industries, Inc.) and Equalizer (Royce Medical
      Co.), and one pair of laboratory shoes (Noveto, Adidas). A force platform and a 6
      camera Vicon motion analysis system were used to collect GRFs and 3D kinematic
      data during the testing session. A one-way repeated measures analysis of variance
      (ANOVA) was used to evaluate selected kinematic, GRF, and joint kinetic variables
      (p<0.05). The results revealed that both short-leg walking boots were effective
      in minimizing ankle eversion and hip adduction. Neither walker increased the
      bimodal vertical GRF peaks typically observed in normal walking. However, they
      did impose a small initial peak (<1BW) earlier in the stance phase. The Gait
      Walker also exhibited a slightly increased vertical GRF during midstance. These
      characteristics may be related to the sole materials/design, the restriction of
      ankle movements, and/or the elevated heel heights of the tested walkers. Both
      walkers appeared to increase the demand on the knee extensors while they
      decreased the demand of the knee and hip abductors based on the joint kinetic
      results.

PMID- 16414264
TI  - Efficient approach to acyloxymethyl esters of nalidixic acid and in vitro
      evaluation as intra-ocular prodrugs.
AB  - Various alkylcarbonyloxymethyl esters of nalidixic acid ranging from 3 to 15
      carbon units in the pro-moiety have been prepared and assessed as potential
      prodrugs. Their chromatographic retention factors k', silicone oil solubilities
      and in vitro conversion to nalidixic acid by a commercial esterase were
      determined together with their in vitro antimicrobial activity and cytotoxicity.
      The preliminary results suggest that silicone oil may have potential for the
      intra-ocular delivery of antibacterial compounds. Moreover, the in vitro release
      rate can be controlled by the lipophilicity of the prodrug.

PMID- 16414265
TI  - Some properties of Ti-related paramagnetic centres relevant for electron spin
      resonance dating of single sedimentary quartz grains.
AB  - We performed Q-band ESR spectroscopy on several single quartz grains from
      different geological deposits. Various properties of Ti-related impurity centres
      in quartz relevant for ESR dating were studied. It will be shown that some
      properties, such as sensitivity change and response to artificial gamma
      irradiation, may vary from grain to grain. It is concluded that single grain ESR
      dating is feasible at a pure experimental level.

PMID- 16414266
TI  - Adjuvant chemotherapy for completely resected non-small cell lung cancer: a
      systematic review.
AB  - PURPOSE: To conduct a systematic review and to evaluate the impact of
      postoperative adjuvant chemotherapy on the survival of patients with completely
      resected non-small cell lung cancer. METHODS: Relevant randomized trials and meta
      analyses, published as articles or abstracts, were identified through electronic
      and hand searches by two reviewers. RESULTS: Seven meta-analyses and 26
      randomized trials comparing surgery with or without chemotherapy met the pre
      defined eligibility criteria for the review. The meta-analyses all showed a
      survival advantage for platinum- or UFT-based postoperative chemotherapy,
      although the results did not always achieve statistical significance. The results
      of individual trials were inconsistent, although recent trials have detected a
      large survival advantage with postoperative platinum-based chemotherapy.
      Differences in trial design, patient characteristics, disease stage, use of
      radiotherapy and chemotherapy regimen may explain the variation in results.
      CONCLUSIONS: Postoperative adjuvant platinum-based chemotherapy improves survival
      compared with surgery alone in completely resected non-small cell lung cancer. In
      patients fit for chemotherapy, the survival benefits strongly outweigh the
      adverse effects of the treatment.

PMID- 16414267
TI  - Mucosal inoculation of Lactobacillus expressing hCGbeta induces an anti-hCGbeta
      antibody response in mice of different strains.
AB  - To show that an anti-human chorionic gonadotrophin-beta (hCGbeta) antibody
      response can be induced by inoculating Lb. expressing hCGbeta through different
      mucosal pathways in mice of two strains, female BALB/c and C57BL/6 mice were
      immunized via vaginal, oral or nasal routes with 10(8), 10(9), and
      10(10)Lb.hCGbeta (a recombinant Lactobacillus expressing hCGbeta). The mice were
      immunized twice with a booster in study week 3. An indirect ELISA was used to
      determine anti-hCGbeta IgG and IgA antibodies in vaginal lavage and serum,
      obtained from the 2nd to 8th week after the primary immunization. Flow cytometry
      was used to analyze the lymphocyte proliferation from these tissues, 1 week after
      the primary immunization. The hCGbeta antigen-specific antibody-secreting cells
      of spleen, uterus, and vagina were evaluated by enzyme-linked immunospot assay
      (ELISpot), 2 weeks after the booster. The analysis showed that 10(9) and
      10(10)Lb.hCGbeta inoculations induced similar anti-hCGbeta antibody responses,
      while the three mucosal pathways induced similar antibody responses. The
      antiserum obtained after boosters with 10(9) and 10(10)Lb. hCGbeta was able to
      neutralize more than 100 ng/ml hCG antigen, both in BALB/c and C57BL/6 mice. The
      highest antibody titer induced by vaginal mucosal immunization was stronger than
      that obtained via the other mucosal pathways. The B cells in the vagina appeared
      to proliferate after vaginal immunization (P<0.05). The numbers of anti-hCGbeta
      IgG and IgA antibody-secreting cells in the uterus and vagina were greater than
      in the spleen. Therefore, the vaginal mucosal route appears to be a better
      immunization pathway to induce higher anti-hCGbeta antibody levels in the
      reproductive tract.

PMID- 16414268
TI  - Mechanisms for inducing nasal mucosal tolerance in experimental autoimmune
      uveoretinitis.
AB  - Delivering soluble (auto) antigenic peptides via the naso-respiratory route
      induces tolerance to that peptide and suppression of experimental models of
      autoimmune disease. In the normal lung, respiratory tract dendritic cells (RTDCs)
      efficiently endocytose soluble antigens, migrate to regional lymph nodes and
      present peptide to T cells that subsequently become tolerant. This article
      describes protocols for inducing tolerance via the naso-respiratory tract in
      experimental autoimmune uveoretinitis (EAU); for the isolation of RTDCs to
      facilitate definition of, and conditions for, maturation and activation of cells;
      and to test RTDC ability to induce tolerance in murine EAU when adoptively
      transferred.

PMID- 16414269
TI  - Oral delivery of tetanus toxoid using vesicles containing bile salts (bilosomes)
      induces significant systemic and mucosal immunity.
AB  - Protein antigens administered via the oral route are exposed to a hostile
      environment in the gastrointestinal tract, consisting of digestive enzymes and a
      range of pH (1-7.5). Using a delivery system can afford protection to entrapped
      components against degradation and permit delivery of antigen to the cells
      responsible for generating local and systemic immune responses. In this
      comparative study, mice were immunised orally with tetanus toxoid (40 or 200
      microg dose/mouse, four doses in total) entrapped in non-ionic surfactant
      vesicles formulated with bile salts (bilosomes). The higher entrapped dose (BV
      TT, 200 microg) induced IgG1 by study week 3 to similar levels to those observed
      with subcutaneous un-entrapped TT at the lower (<50 microg) dose. However, both
      bilosome formulations (BV-TT, low, and high doses), though not un-entrapped TT,
      caused a rise in the numbers of IgA positive plasma cells observed in the small
      intestine, primarily in the first 15 cm of the small intestine.

PMID- 16414270
TI  - Rational design of Salmonella-based vaccination strategies.
AB  - A permanently growing body of information is becoming available about the quality
      of protective immune responses induced by mucosal immunization. Attenuated live
      bacterial vaccines can be administered orally and induce long-lasting protective
      immunity in humans without causing major side effects. An attenuated Salmonella
      enterica serovar Typhi strain is registered as live oral vaccine against typhoid
      fever and has been in use for more than two decades. Recombinant attenuated
      Salmonella strains are also an attractive means of delivering heterologous
      antigens to the immune system, thereby, stimulating strong mucosal and systemic
      immune responses and consequently provide an efficient platform technology to
      design novel vaccination strategies. This includes the choice of heterologous
      protective antigens and their expression under the control of appropriate
      promoters within the carrier strain. The availability of well-characterized
      attenuated mutants of Salmonella concomitantly supports fine tuning of immune
      response triggered against heterologous antigens. Exploring different mucosal
      sites as a potential route of immunization has to be taken into account as an
      additional important way to modulate immune responses according to clinical
      requirements. This article focuses on the rational design of strategies to
      modulate appropriate immunological effector functions on the basis of selection
      of (i) attenuating mutations of the Salmonella strains, (ii) specific expression
      systems for the heterologous antigens, and (iii) route of mucosal administration.

PMID- 16414271
TI  - Thermosensitive and mucoadhesive delivery systems of mucosal vaccines.
AB  - Mucosal vaccination is emerging as a potential administration route for eliciting
      antigen-specific mucosal and systemic immunogenicity. Most mucosal vaccines have
      been administered in a phosphate-buffered saline vehicle that may limit the
      exposure of antigens to the mucosal surfaces and result in poor immunogenicity.
      To improve the potency of the mucosal vaccines, we have developed mucosal vaccine
      delivery systems that might prevent leakage and increase retention of vaccines on
      mucosal surfaces. Thermosensitive polymers have been used to reduce the leakage
      problems of nasal or vaginal vaccines, while mucoadhesive polymers have been
      employed to increase the mucosal contact of the vaccines. Here, we describe the
      formulation and delivery methods of mucosal vaccines using thermosensitive and
      mucoadhesive polymers.

PMID- 16414272
TI  - Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made
      from food-grade bacteria.
AB  - Mucosal immunization with subunit vaccines requires new types of antigen delivery
      vehicles and adjuvants for optimal immune responses. We have developed a non
      living and non-genetically modified gram-positive bacterial delivery particle
      (GEM) that has built-in adjuvant activity and a high loading capacity for
      externally added heterologous antigens that are fused to a high affinity binding
      domain. This binding domain, the protein anchor (PA), is derived from the
      Lactococcus lactis AcmA cell-wall hydrolase, and contains three repeats of a LysM
      type cell-wall binding motif. Antigens are produced as antigen-PA fusions by
      recombinant expression systems that secrete the hybrid proteins into the culture
      growth medium. GEM particles are then used as affinity beads to isolate the
      antigen-PA fusions from the complex growth media in a one step procedure after
      removal of the recombinant producer cells. This procedure is also highly suitable
      for making multivalent vaccines. The resulting vaccines are stable at room
      temperature, lack recombinant DNA, and mimic pathogens by their bacterial size,
      surface display of antigens and adjuvant activity of the bacterial components in
      the GEM particles. The GEM-based vaccines do not require additional adjuvant for
      eliciting high levels of specific antibodies in mucosal and systemic
      compartments.

PMID- 16414273
TI  - A sheep cannulation model for evaluation of nasal vaccine delivery.
AB  - We have developed and validated a novel model to investigate the efficacy of
      nasal vaccine delivery. Based on lymphatic cannulation of the tracheal lymph
      trunk of sheep, the model allows collection of lymph draining from the Nasal
      Associated Lymphoid Tissue. The model is suitable for determining both the amount
      of material that is absorbed into the lymphatic system, following intra-nasal
      delivery and the immune response that occurs following vaccination into the nasal
      area. The cell populations that track in this duct were phenotyped and found to
      be similar to those previously reported to be present in efferent lymph draining
      from peripheral lymph nodes. Following intra-nasal spray, we demonstrated that
      the amount of material recovered in draining lymph is only a very small fraction
      of the total delivered. Nevertheless, intra-nasal spraying of a vaccine could
      activate local immune cells. The method described will be invaluable for
      optimising intra-nasal delivery systems by allowing a separate optimisation of
      vaccine uptake and immune responses induction.

PMID- 16414274
TI  - Functional expression of single-chain variable fragment antibody against c-Met in
      the cytoplasm of Escherichia coli.
AB  - c-Met, a high affinity receptor for hepatocyte growth factor/scatter factor,
      shown to be overexpressed in a variety of malignant cells, is a potential
      biomarker as well as a therapeutic target. Thus, single-chain antibody fragment
      (scFv) specific for c-Met is expected to be efficiently employed in the clinical
      treatment or imaging of many cancer cells. Here, we constructed the expression
      system for anti-c-Met scFv fused with T7 tag at its N-terminus using pET vector
      and investigated the expression conditions to achieve a functional and soluble
      expression of the scFv in the cytoplasm of recombinant Escherichia coli. The
      redox potential of E. coli cytoplasm was the most critical factor for the
      functional expression of anti-c-Met scFv. The employment of a host with oxidizing
      cytoplasm, E. coli trxB/gor double mutant, improved the productivity of
      functional anti-c-Met scFv by approximately 10-fold compared to the production of
      anti-c-Met scFv in the reducing cytoplasm of wild type E. coli. Productivity of
      functional anti-c-Met scFv could be further enhanced by co-expressing molecular
      chaperones such as GroELS, trigger factor, and DsbC with the scFv. Coexpression
      of DsbC increased the yield of functional anti-c-Met scFv about 2.5-fold in the
      cytoplasm of E. coli trxB/gor mutant compared to the production of scFv without
      DsbC coexpression. Lowering the IPTG concentration from 1 to 0.05 mM led to the
      slight enhancement, approximately 1.6-fold, of productivity of functional scFv.
      Although the use of low temperature for anti-c-Met scFv expression increased the
      ratio of soluble scFv fraction to insoluble fraction, productivity of soluble
      scFv decreased owing to the significant reduction of expression rate. The
      addition of 0.5 M sucrose in the medium inhibited the formation of intracellular
      insoluble anti-c-Met scFv. To purify the anti-c-Met scFv simply, we fused
      hexahistidine at the C-terminus of scFv and purified the scFv showing 98% of
      purity through the interaction between Ni2+ and histidine.

PMID- 16414275
TI  - Preterm delivery and age of SIDS death.
AB  - PURPOSE: The aim of the study is to (i) reexamine risk factors for sudden infant
      death syndrome (SIDS) and (ii) describe the relationship between length of
      gestation and age at death from SIDS. METHODS: To evaluate risk factors for SIDS,
      we used multivariable logistic regression and included maternal demographic
      characteristics, maternal health and behavioral factors, and infant
      characteristics, including fetal growth, using US national linked birth and death
      files from 1996 to 1998. We used multivariable linear regression with mean
      postnatal age of death as the outcome of interest, controlling for the factors
      listed (referent length of gestation, 40 to 41 weeks). RESULTS: The crude SIDS
      rate was 0.7 deaths/1000 live births (8199 deaths). Length of gestation was a
      strong risk factor for SIDS, with the adjusted odds ratio (OR) greatest at
      shorter gestations: 28 to 32 weeks (OR, 2.9; 95% confidence interval, 2.6-3.2).
      Infants with gestations of 22 to 27 and 28 to 32 weeks died at mean ages of 20.9
      (SD = 0.8) and 15.3 (SD = 0.5) weeks, respectively (p < or = 0.002). Term infants
      (40 to 41 weeks) died of SIDS at an adjusted mean age of 14.5 (SD = 0.4) weeks.
      CONCLUSIONS: Preterm birth continues to be a strong risk factor for SIDS after
      controlling for fetal growth. With increasing gestational age, mean age of SIDS
      death decreases considerably, with the postnatal age of death of very preterm
      infants 6 weeks later than that of term infants.

PMID- 16414276
TI  - The flagellar attachment zone of Trypanosoma cruzi epimastigote forms.
AB  - The flagellar attachment zone (FAZ) is an adhesion region of Trypanosoma cruzi
      epimastigote forms where the flagellum emerges from the flagellar pocket and
      remains attached to the cell body. This region shows a junctional complex which
      is formed by a linear series of apposed macular structures that are separated by
      amorphous material and clusters of intramembranous particles. Two protein groups
      appear to be important in the FAZ region: a membrane glycoprotein of 72kDa and
      several high molecular weight proteins. To gain a better understanding of the FAZ
      region, we compared wild-type Y strain T. cruzi epimastigotes with a mutant cell
      in which the 72-kDa surface glycoprotein (Gp72), involved in cell body-flagellum
      adhesion, had been deleted by target gene replacement. Using immunofluorescence
      confocal microscopy and electron microscopy techniques to analyze the FAZ region
      the results suggest that, in the absence of Gp72, other proteins involved in the
      formation of FAZ remain concentrated in the flagellar pocket region. The analysis
      of a 3-D reconstruction model of wild-type epimastigotes showed that the
      endoplasmic reticulum and mitochondrion are in intimate association with FAZ, in
      contrast to the null mutant cells where the endoplasmic reticulum was not
      visualized.

PMID- 16414277
TI  - Structure and mechanical properties of the soft zone separating bulk dentin and
      enamel in crowns of human teeth: insight into tooth function.
AB  - The 200-300 microm soft zone of dentin, found beneath enamel in crowns of human
      teeth, is thought to fulfill important roles in tooth function, but little is
      known about its structure-mechanical relations. Scanning electron microscopy
      images of fracture surfaces showed that near the dentino-enamel junction (DEJ), a
      porous reticulate matrix of intertubular-dentin contains tubules with no
      peritubular lining. Peritubular-dentin however is found at some distance from the
      DEJ, and it gradually thickens with increasing depth into the bulk dentin.
      Concurrently, tighter packing of the collagen fibers is observed with a gradual
      increase in mineral deposits on and between the fibers. This structurally graded
      zone is known to be softer when tested for micro-hardness. It undergoes greater
      strain compared to bulk dentin, when measured using Moire interferometry. We
      investigated the deformation and stiffness of this zone by means of non-contact
      laser-speckle interferometry (ESPI), and nanometer-scale deformations were
      tracked during compression-testing performed in water. We report a significantly
      reduced stiffness of this zone compared to bulk dentin, with mid-buccal regions
      of teeth averaging 3.5 GPa compared with 9.7 GPa in mid-lingual regions. Our
      results support and expand upon the hypothesis that the durability of the whole
      tooth relies upon a bucco-lingual asymmetric matching of stiffness by means of an
      interphase: a cushioning soft layer between enamel and bulk dentin.

PMID- 16414278
TI  - EEG reveals the effect of fMRI scanner noise on noise-sensitive subjects.
AB  - One drawback of fMRI is that subjects must endure intense noise during testing.
      This may be annoying to some people and acceptable to others. The aim of this
      study was to examine, by means of event-related potentials (ERPs), the possible
      influence of this noise on brain activity while performing a mental reasoning
      task. Subjects carrying out tasks in a silent environment were compared with two
      groups executing the same tasks in an "fMRI-like" noisy environment, one of which
      consisted of subjects who were annoyed by the noise and the other of subjects who
      tolerated it easily. Subjects who were annoyed performed less well (i.e.,
      produced more errors compared to the "no noise" group) and "not annoyed" subjects
      showed a speed-accuracy trade-off (i.e., reacted faster but made more errors
      compared to "no noise" subjects). Noise led to more pronounced N1 and P2 peaks
      but attenuated N2. As early ERP components are influenced by attention, this
      observation most likely reflects different attentional requirements. The slow
      cortical negative shift during task processing was significantly attenuated with
      "annoyed" subjects compared to "not annoyed" subjects. Emotion-related
      subcortical structures may be responsible for the observed difference. These
      findings suggest that individual reactions to fMRI scanner noise should be taken
      into account when designing fMRI studies and interpreting results.

PMID- 16414279
TI  - Neural substrates of cross-modal olfactory recognition memory: an fMRI study.
AB  - Ten young adults (aged 20 to 25 years) participated in a functional Magnetic
      Resonance Imaging (fMRI) study to investigate neural substrates of cross-modal
      olfactory recognition memory. Before entering the scanner, participants were
      presented with 16 familiar odors selected from the COLT (Murphy, C., Nordin, S.,
      Acosta, L., 1997. Odor learning, recall, and recognition memory in young and
      elderly adults. Neuropsychology 11, 126-137) and were then scanned for 3 runs
      according to a paradigm derived from Stark and Squire (Stark, C.E., Squire, L.R.,
      2000. Functional magnetic resonance imaging (fMRI) activity in the hippocampal
      region during recognition memory. J. Neurosci. 20, 7776-7781). During each run,
      participants were shown names of odors presented (targets) or not presented
      (foils) at encoding. Participants distinguished targets from foils via button
      press. Each run alternated 4 'ON' periods containing 7 targets and 2 foils (36 s)
      and 4 'OFF' periods with 7 foils and 2 targets (36 s). Data were processed with
      AFNI (Cox, R.W., 1996. AFNI: software for analysis and visualization of
      functional magnetic resonance neuroimages. Comput. Biomed. Res. 29, 162-173) and
      compared ON and OFF periods, extracting activation in regions that responded
      during the cross-modal olfactory recognition memory task. Group analysis showed
      that regions activated during the first run included right hippocampus,
      piriform/amygdalar area, superior temporal gyrus, anterior cingulate gyrus,
      inferior frontal/orbitofrontal gyrus, superior/medial frontal gyrus, and
      bilateral parahippocampal gyrus, inferior parietal lobule, supramarginal gyrus,
      cerebellum, lingual/fusiform area and middle/posterior cingulate gyrus. Region of
      interest analysis showed that degree of activation significantly decreased from
      run 1 to run 3 in the right hippocampus, fusiform gyrus, lingual gyrus,
      parahippocampal gyrus and middle frontal gyrus but not in other regions,
      suggesting that these regions sustain a specific function in olfactory
      recognition memory that attenuates as foils become more familiar with repeated
      presentation.

PMID- 16414280
TI  - Using fMRI to decompose the neural processes underlying the Wisconsin Card
      Sorting Test.
AB  - The specific role of particular cerebral regions with regard to executive
      functions remains elusive. We conducted a functional magnetic resonance imaging
      (fMRI) study to segregate different network components underlying the Wisconsin
      Card Sorting Test (WCST), a test widely applied clinically to assess executive
      abilities. Three different test variants of the WCST, differing in task
      complexity (A > B > C), were contrasted with a high-level baseline condition
      (HLB). Cognitive subcomponents were extracted in a serial subtraction approach (A
      C, A-B, B-C). Imaging data were further subjected to a correlational analysis
      with individual behavioral parameters. Contrasting A with the HLB revealed the
      entire neural network underlying WCST performance, including frontoparietal
      regions and the striatum. Further analysis showed that, within this network,
      right ventrolateral prefrontal cortex related to simple working memory
      operations, while right dorsolateral prefrontal cortex related to more
      complex/manipulative working memory operations. The rostral anterior cingulate
      cortex (ACC) and the temporoparietal junction bilaterally represented an
      attentional network for error detection. In contrast, activation of the caudal
      ACC and the right dorsolateral prefrontal cortex was associated with increased
      attentional control in the context of increasing demands of working memory and
      cognitive control. Non-frontal activations were found to be related to
      (uninstructed relative to instructed) set-shifting (cerebellum) and working
      memory representations (superior parietal cortex, retrosplenium). The data
      provide neural correlates for the different cognitive components involved in the
      WCST. They support a central role of the right dorsolateral prefrontal cortex in
      executive working memory operations and cognitive control functions but also
      suggest a functional dissociation of the rostral and caudal ACC in the
      implementation of attentional control.

PMID- 16414281
TI  - Neural correlates of social and nonsocial emotions: An fMRI study.
AB  - Common theories of emotion emphasize valence and arousal dimensions or
      alternatively, specific emotions, and the search for the underlying
      neurocircuitry is underway. However, it is likely that other important dimensions
      for emotional neurocircuitry exist, and one of them is sociality. A social
      dimension may code whether emotions are addressing an individual's
      biological/visceral need versus more remote social goals involving semantic
      meaning or intentionality. Thus, for practical purposes, social emotions may be
      distinguished from nonsocial emotions based in part on the presence of human
      forms. In the current fMRI study, we aimed to compare regional coding of the
      sociality dimension of emotion (nonsocial versus social) versus the valence
      dimension of emotion (positive versus negative). Using a novel fMRI paradigm,
      film and picture stimuli were combined to induce and maintain four emotions
      varying along social and valence dimensions. Nonsocial emotions of positively
      valenced appetite and negatively valenced disgust and social emotions of
      positively valenced joy/amusement and negatively valenced sadness were studied.
      All conditions activated the thalamus. Appetite and disgust activated posterior
      insula and visual cortex, whereas joy/amusement and sadness activated extended
      amygdala, superior temporal gyrus, hippocampus, and posterior cingulate.
      Activations within the anterior cingulate, nucleus accumbens, orbitofrontal
      cortex, and amygdala were modulated by both social and valence dimensions.
      Overall, these findings highlight that sociality has a key role in processing
      emotional valence, which may have implications for patient populations with
      social and emotional deficits.

PMID- 16414282
TI  - Lagged covariance structure models for studying functional connectivity in the
      brain.
AB  - Most cognitive processes are supported by large networks of brain regions. To
      describe the operation of these networks, it is critical to understand how
      individual areas are functionally connected. Here, we establish a statistical
      framework for studying effective and functional brain connectivity, using data
      obtained with a relatively new neuroimaging method, the event-related optical
      signal (EROS). The novelty of our approach is the use of timing information (in
      the form of lagged cross-correlations) in interpreting the connections between
      areas. Interpretation of lagged cross-correlations exploits the combination of
      spatial and temporal resolution provided by EROS. In this paper, we apply dynamic
      factor analysis as a method for testing various structural models on the lagged
      covariance matrices derived from the EROS data. We first illustrate the approach
      by testing a simple path model of neural activity propagation from area V1 to V3
      in a visual stimulation task. We then build more complex structural equation
      models with latent variables, describing both within-hemisphere integrity, and
      interactions between the two hemispheres, to interpret data from a second task
      involving inter-hemispheric competition. The results demonstrate how the
      integrity of anatomical connections between the two hemispheres explains
      different patterns of cross-hemispheric interactions. This approach allows for
      fitting brain imaging data to complex models that capture dynamic cognitive
      processes as they rapidly evolve over time.

PMID- 16414283
TI  - Linear aspects of transformation from interictal epileptic discharges to BOLD
      fMRI signals in an animal model of occipital epilepsy.
AB  - Epileptic disorders manifest with seizures and interictal epileptic discharges
      (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may
      be critical for understanding epileptogenesis. Despite a known linear coupling of
      the neurovascular elements in normal brain tissues, previous simultaneous
      electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies
      have shown variable correlations between epileptic discharges and blood
      oxygenation level-dependent (BOLD) response, partly because most previous studies
      assumed particular hemodynamic properties in normal brain tissue. The occurrence
      of IEDs in human subjects is unpredictable. Therefore, an animal model with
      reproducible stereotyped IEDs was developed by the focal injection of penicillin
      into the right occipital cortex of rats anesthetized with isoflurane.
      Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A
      hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of
      fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear
      autoregression with exogenous input (ARX) model was used to estimate the
      hemodynamic impulse response function (HIRF) based on the data from simultaneous
      EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary
      visual cortex and bilateral visual association cortices were consistently coupled
      to IEDs. The linear ARX model was applied here to confirm that a linear transform
      can be used to study the correlation between BOLD signal and its corresponding
      neural activity in this animal model of occipital epilepsy.

PMID- 16414285
TI  - Phylogeny and biogeography of the Petaurista philippensis complex (Rodentia:
      Sciuridae), inter- and intraspecific relationships inferred from molecular and
      morphometric analysis.
AB  - With modified DNA extraction and purification protocols, the complete cytochrome
      b gene sequences (1140 bp) were determined from degraded museum specimens.
      Molecular analysis and morphological examination of cranial characteristics of
      the giant flying squirrels of Petaurista philippensis complex (P. grandis, P.
      hainana, and P. yunanensis) and other Petaurista species yielded new insights
      into long-standing controversies in the Petaurista systematics. Patterns of
      genetic variations and morphological differences observed in this study indicate
      that P. hainana, P. albiventer, and P. yunanensis can be recognized as distinct
      species, and P. grandis and P. petaurista are conspecific populations.
      Phylogenetic relationships reconstructed by using parsimony, likelihood, and
      Bayesian methods reveal that, with P. leucogenys as the basal branch, all
      Petaurista groups formed two distinct clades. Petaurista philippensis, P.
      hainana, P. yunanensis, and P. albiventer are clustered in the same clade, while
      P. grandis shows a close relationship to P. petaurista. Deduced divergence times
      based on Bayesian analysis and the transversional substitution at the third codon
      suggest that the retreating of glaciers and upheavals or movements of tectonic
      plates in the Pliocene-Pleistocene were the major factors responsible for the
      present geographical distributions of Petaurista groups.

PMID- 16414284
TI  - Cortical layer-dependent BOLD and CBV responses measured by spin-echo and
      gradient-echo fMRI: insights into hemodynamic regulation.
AB  - Spatial specificity of functional magnetic resonance imaging (fMRI) signals to
      sub-millimeter functional architecture remains controversial. To investigate this
      issue, high-resolution fMRI in response to visual stimulus was obtained in
      isoflurane-anesthetized cats at 9.4 T using conventional gradient-echo (GE) and
      spin-echo (SE) techniques; blood oxygenation-level dependent (BOLD) and cerebral
      blood volume (CBV)-weighted data were acquired without and with injection of 10
      mg Fe/kg monocrystalline iron oxide nanoparticles (MION), respectively. Studies
      after MION injection at two SE times show that the T2' contribution to SE fMRI is
      minimal. GE and SE BOLD changes were spread across the cortical layers. GE and SE
      CBV-weighted fMRI responses peaked at the middle cortical layer, which has the
      highest experimentally-determined microvascular volume; full-width at half
      maximum was <1.0 mm. Parenchymal sensitivity of GE CBV-weighted fMRI was
      approximately 3 times higher than that of SE CBV-weighted fMRI and approximately
      1.5 times higher than that of BOLD fMRI. It is well known that GE CBV-weighted
      fMRI detects a volume change in vessels of all sizes, while SE CBV-weighted fMRI
      is heavily weighted toward microvascular changes. Peak CBV change of 10% at the
      middle of the cortex in GE measurements was 1.8 times higher than that in SE
      measurements, indicating that CBV changes occur predominantly for vasculature
      connecting the intracortical vessels and capillaries. Our data supports the
      notion of laminar-dependent CBV regulation at a sub-millimeter scale.

PMID- 16414287
TI  - On conditioned reconstruction, gene content data, and the recovery of fusion
      genomes.

PMID- 16414286
TI  - Comparative analysis of a translocated copy of the trnK intron in carnivorous
      family Nepenthaceae.
AB  - During phylogenetic analysis of the Nepenthaceae cpDNA trnK intron, it became
      apparent that a second non-functional copy of the locus was present in most of
      the investigated taxa. The translocation event was older than the radiation of
      all recent Nepenthaceae, and the translocated pseudogenized copy was conserved in
      nearly all members of the plant family. Using single chloroplast PCR and inverse
      PCR, we could exclude a plastom location for the second copy. Although
      translocation into the nucleus is possible, mitochondrial localization seems more
      likely based on these data. In total, the translocated sequence contained at
      least 3525 base pairs (bp) that were homologous to the Spinacia oleracea
      chloroplast genome. Comparative phylogenetic analysis of the non-functional copy
      revealed a high amount of homoplasies compared to topologies from the cpDNA trnK
      intron phylogenetic reconstruction. Therefore, this copy proved to be
      insufficient for phylogenetic reconstruction of the family. Since two different
      paralogs of the non-functional copy were found in one species, it is feasible
      that different paralogs were conserved in different groups and that paralogous
      sequences were included in the data matrix. These data demonstrate that
      phylogenetic analyses of pseudogenized copies of phylogenetically relevant loci
      should be performed with great caution. In addition, pseudogenized copies can
      exist in nearly every member of a plant family, and can be PCR-amplified at
      levels comparable to the specific copy. In this case, the inclusion of such
      copies can easily remain unnoticed, thus leading to faulty hypotheses.

PMID- 16414288
TI  - Mitochondrial phylogeny of African wood mice, genus Hylomyscus (Rodentia,
      Muridae): implications for their taxonomy and biogeography.
AB  - This paper investigates the usefulness of two mitochondrial genes (16S rRNA and
      cytochrome b) to solve taxonomical difficulties within the genus Hylomyscus and
      to infer its evolutionary history. Both genes proved to be suitable molecular
      markers for diagnosis of Hylomyscus species. Nevertheless the resolving powers of
      these two genes differ, and with both markers (either analyzed singly or in
      combination), some nodes remain unresolved. This is probably related to the fact
      that the species emerged during a rapid diversification event that occurred 2-6
      Myr ago (4-5 Myr ago for most divergence events). Our molecular data support the
      recognition of an "aeta" group, while the "alleni" and "parvus" groups are not
      fully supported. Based on tree topology and genetic divergence, two taxa
      generally recognized as subspecies should be elevated at the species level (H.
      simus and H. cf kaimosae). H. stella populations exhibit ancient haplotype
      segregation that may represent currently unrecognized allopatric species. The
      existence of cryptic species within H. parvus is questioned. Finally, three
      potentially new species may occur in West Central Africa. The Congo and Oubangui
      Rivers, as well as the Volta and Niger Rivers and/or the Dahomey gap could have
      formed effective barriers to Hylomyscus species dispersal, favoring their
      speciation in allopatry. The pronounced shifts in African climate during the late
      Pliocene and Miocene, which resulted in major changes in the distribution and
      composition of the vegetation, could have promoted speciation within the genus
      (refuge theory). Future reports should focus on the geographic distribution of
      Hylomyscus species in order to get a better understanding of the evolutionary
      history of the genus.

PMID- 16414289
TI  - A cellular model system for expression studies of coagulation proteins.
AB  - INTRODUCTION: The development of novel antithrombotic agents directly affecting
      gene expression requires well established, reliable and useful in vitro model
      systems for initial validation of drug effects. Since most proteins involved in
      coagulation are synthesized by the liver, the hepatoblastoma cell line Hep G2 is
      introduced, here, as a model system to test nucleic acid based coagulation
      inhibitors. METHODS: Hep G2 cells were characterized with respect to prothrombin,
      tissue factor and factor VIII expression in dependence of cell culture
      conditions. Reliable enzyme linked immuno sorbent assays as well as viability
      tests were introduced that allow drug screening procedures with multiple probes
      in microplate format. Furthermore, a multiplex PCR-procedure has been presented
      that offers the possibility to simultaneously detect the effects of a selected
      compound on two coagulation proteins in comparison to a house keeping gene.
      RESULTS: Hep G2 cells were not affected in viability by cell culture conditions,
      while proliferation and the expression patterns of some coagulation factors were
      affected by the adhesion factor collagen. The prothrombin expression
      characteristics allowed us to choose a specific time point for the transfection
      of Hep G2 cells with prothrombin specific antisense oligonucleotides. Antisense
      oligonucleotides inhibited prothrombin expression independent from culture
      conditions and the effects were detected on protein-and mRNA-level. DISCUSSION:
      Nucleic acid based agents require cellular in vitro model systems since they
      affect the process of gene expression and not the gene product. Hep G2 cells are
      a useful model to study effects of novel nucleic acid based coagulation
      inhibitors with an antisense mechanism of action on protein and mRNA level.

PMID- 16414290
TI  - Prognostic factors for surgery of neocortical temporal lobe epilepsy.
AB  - OBJECTIVES: In the current classification of epilepsies two forms of temporal
      lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed
      at identifying prognostic factors for the surgical outcome of lesional
      neocortical TLE. METHODS: We included consecutive patients who had undergone
      presurgical evaluation including ictal video-EEG and high-resolution MRI, who had
      TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and
      who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion
      criteria. Twenty of them became postoperatively seizure-free. Patients' mean age
      was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years.
      We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on
      MRI (p=0.005) were associated with non-seizure-free outcome, while
      lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013),
      and a favorable seizure situation at the 6-month postoperative evaluation were
      associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate
      analysis indicated that the side of surgery was not an independent predictor.
      CONCLUSION: More than two-thirds of the patients with neocortical TLE became
      seizure-free postoperatively. Lateralized/localized EEG seizure pattern and
      tumors on the MRI were associated with postoperative seizure-freedom, while FCD
      were associated with a poor outcome. The 6-month postoperative outcome is a
      reliable predictor for the long-term outcome.

PMID- 16414291
TI  - Effects of common anti-epileptic drug monotherapy on serum levels of
      homocysteine, vitamin B12, folic acid and vitamin B6.
AB  - There is emerging evidence to support the unfavorable effects of some anti
      epileptic drugs on the plasma homocysteine concentrations. Elevated homocysteine
      levels induced by anti-epileptic drug administration can theoretically increase
      not only the risk of vascular occlusive diseases, but also the risk of resistance
      to anti-epileptics and development of refractory epilepsy. To investigate the
      effect of common anti-epileptic drugs on the homocysteine metabolism, a total of
      75 epileptic patients receiving phenytoin (n=16), carbamazepine (n=19), or
      valproic acid (n=22) and no anti-epileptic drug (n=18) were enrolled. Eleven age-
      and sex-matched healthy subjects served as the control group. Blood
      concentrations of homocysteine, folic acid, Vitamin B12 and pyridoxal 5'
      phosphate (active circulating form of Vitamin B6) were measured. Compared to the
      control group, epileptic patients on anti-epileptic drug had higher blood levels
      of homocysteine. No difference in homocysteine concentrations was observed among
      epileptic patients in terms of the anti-epileptic drug used. Patients receiving
      phenytoin had significantly lower folic acid levels and those receiving
      carbamazepine had marginally lower pyridoxal 5'-phosphate levels in comparison
      with those using other anti-epileptic drugs. A negative correlation between
      homocysteine and folic acid concentrations was detected in epileptic patients on
      anti-epileptic drug. The duration of anti-epileptic drug use was correlated to
      the decrease of folic acid levels, but not with changes observed in homocysteine,
      Vitamin B12 and pyridoxal 5'-phosphate levels. No relationship between seizure
      frequency and homocysteine levels was observed in epileptic patients. Our results
      confirm that common anti-epileptic drugs has disadvantageous effects on
      homocysteine status. Because there was no significant change in homocysteine
      concentrations in epileptic patients who were not receiving an anti-epileptic
      drug, and no positive correlation between seizure frequency and homocysteine
      levels, we suggest that increase of homocysteine levels may be due to anti
      epileptic drug use, rather than being epileptic in origin. Additionally, the
      underlying mechanism for homocysteine increase seems to be a decrease of cofactor
      molecules in patients using carbamazepine and phenytoin (pyridoxal 5'-phosphate
      and folic acid, respectively). However, changes observed are not related to the
      alteration in the levels of cofactors and remain unclear in the patients using
      valproic acid.

PMID- 16414293
TI  - Chronic inflammation, immune response, and infection in abdominal aortic
      aneurysms.
AB  - Abdominal aortic aneurysms (AAA) are associated with atherosclerosis, transmural
      degenerative processes, neovascularization, decrease in content of vascular
      smooth muscle cells, and a chronic infiltration, mainly located in the outer
      aortic wall. The chronic infiltration consists mainly of macrophages,
      lymphocytes, and plasma cells. The dominant cells are Th2 restricted CD3+
      lymphocytes expressing interleukine 4, 5, 8, and 10, and tumor necrosis factor
      alpha for regulation of the local immune response. They also produce interferon
      gamma and CD40 ligand to stimulate surrounding cells to produce matrix
      metalloproteases and cysteine proteases for aortic matrix remodeling. The
      lymphocyte activation may be mediated by microorganisms as well as autoantigens
      generated from vascular structural proteins, perhaps through molecular mimicry.
      As in autoimmune diseases, the risk of AAA is increased by certain genotypes
      concerning human leucocyte antigen class II. These types are also associated with
      increased aneurysmal inflammation indicating a genetic susceptibility to aortic
      inflammation. Chlamydia pneumoniae is often detected in AAA but the validity of
      the methods can be questioned, and two small antibiotic trials have been
      disappointing. However, serum antibodies against C. pneumoniae have been
      associated with AAA growth and cross-react with AAA wall proteins. Thus, immune
      responses mediated by microorganisms and autoantigens may play a pivotal role in
      AAA pathogenesis.

PMID- 16414292
TI  - Comparison of gene expression profile between human chondrons and chondrocytes: a
      cDNA microarray study.
AB  - OBJECTIVE: The chondron is a basic unit of articular cartilage that includes the
      chondrocyte and its pericellular matrix (PCM). This current study was designed to
      investigate the effects of the chondron PCM on the gene expression profile of
      chondrocytes. DESIGN: Chondrons and chondrocytes were enzymatically isolated from
      human articular cartilage, and maintained in pellet culture. Pellets of chondrons
      or chondrocytes were collected at days 1, 3 and 5 for cDNA microarray analysis.
      RESULTS: In comparison with chondrocytes alone, chondrons had 258 genes, in a
      broad range of functional categories, either up- or downregulated at the three
      time points tested. At day 1, 26 genes were significantly upregulated in
      chondrons and four downregulated in comparison to chondrocytes. At day 3, the
      number of upregulated chondron genes was 97 and the number downregulated was 43.
      By day 5, there were more downregulated genes (56) than upregulated genes (32) in
      chondrons. Upregulation of a group of heat shock proteins (HSPA1A, HSPA2 and
      HSPA8) in chondrons was validated by real time reverse transcription polymerase
      chain reaction (RT-PCR). Genes related to chondrocyte hypertrophy and
      dedifferentiation such as SSP1 and DCN were downregulated in chondrons as
      compared to the expression in chondrocytes. CONCLUSION: The presence of the PCM
      in chondrons has a profound influence on chondrocyte gene expression.
      Upregulation of the heat shock protein 70 may contribute to the robustness and
      active matrix production of chondrons. The intact PCM may further stabilize the
      phenotype of chondrocytes within chondrons.

PMID- 16414294
TI  - Total laparoscopic aortic repair for occlusive and aneurysmal disease: first 95
      cases.
AB  - OBJECTIVES: To analyze the outcome of our preliminary experience with total
      laparoscopic aortic repair in patients with occlusive or aneurysmal disease.
      MATERIAL AND METHODS: From September 2002 to April 2005, we performed 95
      consecutive total laparoscopic aortic repair procedures including 72 for aortic
      occlusive disease (group A) and 23 for abdominal aortic aneurysm (group B).
      RESULTS: In group A, mean operating time was 216+/-50 min with a mean clamp time
      of 57+/-21 min and surgical conversion was required in two cases (2.7%). No
      postoperative death occurred but there were three postoperative complications
      necessitating re-intervention (retroperitoneal hematoma, embolic ischemia, and
      early prosthetic infection). Mean duration of hospitalization was 8 days (range,
      5-42 days). All grafts were patent at 2 months. In group B, mean operating time
      was 251+/-57 min with a mean clamp time of 101+/-15 min and surgical conversion
      was required in seven cases (30%). There was one postoperative death (4.3%) due
      to pulmonary embolism and one non-fatal complication (retroperitoneal hematoma).
      Mean duration of hospitalization was 6.4 days (range, 4-12 days). All grafts were
      patent at 2 months. CONCLUSION: Total laparoscopic repair is feasible and safe
      for occlusive and aneurysmal aortic disease. Operators must acquire technical
      skills using simulators.

PMID- 16414295
TI  - Reduction of human experimental muscle pain by alfentanil and morphine.
AB  - Musculoskeletal pain is a major clinical problem. By using various experimental
      models in humans, the understanding of the basic mechanisms behind muscle pain
      can increase, thereby giving hope for new and optimized treatment. Opioids are
      increasingly often used to treat muscle pain. There are, however, a limited
      number of previous studies on opioids and muscle pain, most of them using a
      relative low, single dose. Therefore, we wanted to further study the effect of
      two rather high doses of alfentanil (25 and 75ng/ml) and morphine (0.14 and
      0.28mg/kg) in human volunteers. The study consisted of two parallel studies with
      morphine and alfentanil, respectively, and was conducted as randomized, double
      blinded, placebo-controlled, 3-way cross-over. We used intramuscular infusion of
      hypertonic saline and intramuscular electrical stimulation to induce experimental
      pain. Visual analog scale (VAS)-score, intramuscular electrical pain thresholds
      and pain area (local and referred) were measured. Both alfentanil and morphine at
      their highest doses induced a 6 to 7-fold increase in pain thresholds to single
      and repetitive (5 stimulations, 2Hz) electrical stimulation. Alfentanil and
      morphine also reduced VAS score about 4 to 5-fold during suprathreshold electric
      stimulation and during infusion of hypertonic saline. None of the drugs decreased
      referred pain. There were no apparent differences between the drugs, in terms of
      effect or adverse reactions. In conclusion, this is the first study to compare
      two high doses of alfentanil and morphine on experimental muscle pain in humans.
      Both alfentanil and morphine reduced experimental muscle pain. There were no
      indications of any true pharmacodynamic differences between the two drugs.

PMID- 16414296
TI  - A three-dimensional in vitro model of angiogenesis in the airway mucosa.
AB  - Bronchial asthma is an inflammatory disease characterized by chronic intermittent
      bronchoconstriction. A key feature of the disease is structural changes in the
      airway wall (airway remodeling) consistent with tissue growth and chronic wound
      healing including angiogenesis. The epithelium directs mesenchymal processes
      during both embryogenesis and wound healing, and thus we hypothesized that the
      bronchial epithelium plays a critical role in directing angiogenesis. To study
      angiogenesis in the airways, we have developed a three-dimensional (3-D) in vitro
      model of the airway mucosa that consists of normal differentiated human bronchial
      epithelial cells (NHBE), normal human lung fibroblasts (NHLF), and human
      umbilical vein endothelial cells (HUVEC). The HUVEC are coated on dextran beads
      and suspended in a fibrin gel approximately 2mm beneath a confluent monolayer of
      NHLF which are just beneath the confluent monolayer of differentiated NHBE. In
      the presence of fibroblasts, visible capillaries reaching lengths of up to 1mm
      sprout from the HUVEC-coated beads. Over 11 days in culture, the bronchial
      epithelium produces transforming growth factor-beta2 (TGFbeta2, 60pg/ml),
      significantly increases vascular endothelial growth factor (VEGF) more than 6
      fold to a concentration of 1.85ng/ml, but does not significantly impact total
      network formation. Exogenous TGFbeta2 stimulates VEGF production in a dose
      dependent fashion (0-400pg/ml) through a MAPK-dependent pathway, but also
      inhibits capillary network formation. We conclude that the bronchial epithelium
      produces biologically relevant concentrations of VEGF and TGFbeta2 in a 3-D model
      of the airway mucosa that may be useful in probing mechanisms of angiogenesis in
      asthma.

PMID- 16414297
TI  - Airway blood flow reactivity in smokers.
AB  - Cigarette smoking has been associated with impaired endothelium-dependent
      relaxation responses in the brachial and coronary arteries (endothelial
      dysfunction). The aim of the present study was to determine if the airway
      circulation is also affected and if airway treatment has an effect on endothelial
      function. Airway blood flow (Q(aw)) responses to inhaled albuterol as an index of
      endothelial function were measured in age-matched healthy current smokers,
      healthy ex-smokers, ex-smokers with COPD and healthy lifetime non-smokers; in the
      ex-smokers with COPD, the albuterol responsiveness was repeated after a 4-week
      treatment with an inhaled glucocorticoid/beta(2)-adrenergic agonist combination
      drug. Mean baseline Q(aw) was similar in the four groups. Albuterol inhalation
      increased mean Q(aw) in lifetime non-smokers (50.1+/-8.3%; p<0.05) and in healthy
      ex-smokers (37.2+/-3.4%; p<0.05) but not in healthy current smokers (13.9+/-3.2%;
      p=NS) and ex-smokers with COPD (9.7+/-4.5%; p=NS). While drug treatment per se
      did not change Q(aw) significantly, it restored albuterol responsiveness (+67.6+/
      11.1%; p<0.05) in the ex-smokers with COPD. Thus, cigarette smoking is associated
      with endothelial dysfunction in the airway, with a partial recovery of
      endothelial function after smoking cessation in healthy ex-smokers but not in ex
      smokers with COPD. In the latter, combined glucocorticoid/beta(2)-adrenergic
      agonist treatment restores albuterol responsiveness.

PMID- 16414298
TI  - Metabolic engineering under uncertainty. I: framework development.
AB  - Standard bioprocess conditions have been widely applied for the microbial
      conversion of raw material to essential industrial products. Successful metabolic
      engineering (ME) strategies require a comprehensive framework to manage the
      complexity embedded in cellular metabolism, to explore the impacts of bioprocess
      conditions on the cellular responses, and to deal with the uncertainty of the
      physiochemical parameters. We have recently developed a computational and
      statistical framework that is based on Metabolic Control Analysis and uses a
      Monte Carlo method to simulate the uncertainty in the values of the system
      parameters [Wang, L., Birol, I., Hatzimanikatis, V., 2004. Metabolic control
      analysis under uncertainty: framework development and case studies. Biophys. J.
      87(6), 3750-3763]. In this work, we generalize this framework to incorporate the
      central cellular processes, such as cell growth, and different bioprocess
      conditions, such as different types of bioreactors. The framework provides the
      mathematical basis for the quantification of the interactions between
      intracellular metabolism and extracellular conditions, and it is readily
      applicable to the identification of optimal ME targets for the improvement of
      industrial processes [Wang, L., Hatzimanikatis, V., 2005. Metabolic engineering
      under uncertainty. II: analysis of yeast metabolism. Submitted].

PMID- 16414300
TI  - Magnetic resonance imaging in spondyloarthropathies.

PMID- 16414299
TI  - [Human immunodeficiency virus, hepatitis C virus and hepatitis B viruses in
      patients with sickle-cell disease in Togo].
AB  - CONTEXT: The clinical features of sickle cell disease (SCD) are vaso-occlusive
      and/or hemolytic crises which treatment may require blood transfusions.
      OBJECTIVE: This study aimed to determine the prevalence of HIV, Hepatitis C Virus
      (HCV) and Hepatitis B Virus (HBV) infections in a population of SCD patients.
      METHODS: All the samples were analyzed by Elisa technique. We studied 119 sera
      for HIV using Elisa and a confirmation test in case of positive Elisa. We
      screened 91 sera for HCV and 119 sera for HBV. RESULTS: The prevalence was 5.04%
      for HIV, 6.5% for HCV and 20.2% for HBs Ag. Homozygous (SS) patients were more
      infected than compound heterozygous patients SC, (p < 0.02). 24.6% of the
      children (0 to 15 years of age) were infected as well as adults (35.5%). The
      Relative Risk to be contaminated was 7.14 for HIV, 4.29 for HCV and 5.43 for HBV
      in transfused compared to non transfused SCD patients. CONCLUSIONS: This high
      infectious risk in SCD patients should lead us to elaborate a better strategy to
      increase the safety of blood transfusion in Togo.

PMID- 16414301
TI  - [Tatoos, piercing: body art? Body damage? Debasement of the body or return to a
      primitive way of life?].
AB  - Tatoos and piercing, though they might appear as something like a trend, if not a
      craze, remain for a majority minority and even fringe practices. For the
      adolescent, questing for his identity (no more a child, not yet an adult), the
      tegmental sign is a way of engraving in the flesh dramatic events of his
      existence. The body mark is a search for independence, a symbolic attainment of
      self-reliance, a way of severing the umbilical cord and of asserting oneself. In
      face of a life no longer under control, the body is an object at hand, on which
      self-will is almost unbridled... These body modifications testify to change.

PMID- 16414302
TI  - [Breast cancer: classified image is not "classified case". Gynecol Obstet Fertil
      2005;33:737-8].

PMID- 16414303
TI  - Effects of bone materials on the screw pull-out strength in human spine.
AB  - A three-dimensional finite element model simulating the threaded connections
      including detailed helix curve for the bone and surgical screw was constructed.
      Validation of the FE model was conducted by comparing the predicted screw pull
      out strength in different foam materials against experimental study. The FE model
      was then further analyzed to investigate the interaction of bone material and
      purchase length on the screw pull-out strength. The results show that failure of
      the connection was due to bone shearing which occurred along a cylindrical
      surface determined by the outer perimeter of the screw. The cortical shell
      resists around 50% of the pull-out strength for a screw of 4mm in major diameter
      and 22 mm in length. The effects of purchase length on the pull-out strength were
      different for different bone material. It is the bone material that determines
      the stability of the inserted surgical screw. The significance of the purchase
      length on the pull-out strength of cortical screw will be much lower than that in
      cancellous bone screw.

PMID- 16414304
TI  - A control theoretic paradigm for cell signaling networks: a simple complexity for
      a sensitive robustness.
AB  - The fields of molecular biology and cell biology are being flooded with complex
      genomic and proteomic datasets of large dimensions. We now recognize that each
      molecule in the cell and tissue can no longer be viewed as an isolated entity.
      Instead, each molecule must be considered as one member of an interacting
      network. Consequently, there is an urgent need for mathematical models to
      understand the behavior of cell signaling networks in health and in disease.

PMID- 16414305
TI  - Severe, persisting, steroid-responsive Dengue myositis.
AB  - OBJECTIVES: Short-term, general muscle affection is frequent in Dengue infection,
      but severe, persisting, myositis has not been reported. STUDY DESIGN: Case
      report. RESULTS: The patient is a 38 years old, HIV-negative male who developed
      sudden-onset fever up to 40.0 degrees C, headache, and sore eyes upon looking
      into light when on holidays in Thailand. One day after onset severe myalgias
      occurred in the shoulder girdle and hip girdle muscles. Clinical examination was
      normal, but blood work revealed elevated creatine-phosphokinase, glutamate
      oxalate transaminase, and glutamate pyruvate transaminase, leucopenia and
      thrombocytopenia. Antibodies against Dengue viruses type 2 and 4 were positive
      and classical Dengue fever was diagnosed. The infection resolved upon symptomatic
      therapy, but myalgias, responsive only to opiates, resolved persistently not
      before the administration of corticosteroids, 2 months after onset. CONCLUSIONS:
      The case shows that Dengue fever may also cause persisting, severe, myositis for
      weeks, which do not respond to non-steroidal analgesics, but promptly to
      corticosteroids.

PMID- 16414306
TI  - Risk factors for human herpesvirus 8 seropositivity in the AIDS Cancer Cohort
      Study.
AB  - BACKGROUND: Cigarette smoking has been associated with a decreased risk for AIDS
      related and classical KS, but whether it is associated with decreased risk of
      human herpesvirus 8 (HHV-8) infection is unknown. STUDY DESIGN: We evaluated
      factors associated with HHV-8 seropositivity in 2795 participants (132 with KS)
      in the National Cancer Institute AIDS Cancer Cohort, including 1621 men who have
      sex with men (MSM), 660 heterosexual men and 514 women. Odds ratios (OR) and 95%
      confidence intervals were estimated using logistic regression models. RESULTS:
      Among non-KS subjects, HHV-8 seropositivity was 6%, 13% and 29% among women,
      heterosexual men and MSM, respectively. HHV-8 seropositivity was decreased in
      heavier (> or =1/2 pack/day) compared to lighter smokers among women (5% versus
      8%; adjusted OR (aOR) 0.4; 95% CI 0.2-0.8) and MSM (27% versus 32%; aOR 0.7; 95%
      CI 0.6-1.0), but not among heterosexual men (12% versus 16%; aOR 0.7; 95% CI 0.4
      1.2). HHV-8 seroprevalence was increased in heavier (> or =1 drink/day) compared
      to lighter consumers of alcohol among women (16% versus 4%; adjusted OR 5.2; 95%
      CI 2.3-12), but not among MSM (33% versus 28%; aOR 1.2; 95% CI 0.9-1.6) or
      heterosexual men (13% versus 13%; aOR 1.1; 95% CI 0.6-2.0). In analyses adjusted
      for smoking and drinking, HHV-8 seropositivity was positively associated with
      chlamydia infection (OR=4.3; 95% CI 1.2-13) and with marital status among women
      p(heterogeneity)=0.03, and with hepatitis (OR=1.6; 95% CI 1.2-2.1), gonorrhea
      (OR=1.5; 95% CI 1.1-1.9), genital warts (OR=1.5; 95% CI 1.1-2.0) and nitrate
      inhalant use (OR=1.7; 95% CI 1.3-2.3) among MSM. CONCLUSIONS: Inverse association
      of HHV-8 seropositivity with cigarette smoking may indicate protective effect of
      tobacco smoke on HHV-8 infection, whereas positive associations with alcohol may
      reflect either behavioral factors or biological effects modulating
      susceptibility. Smoking and drinking may influence KS risk, at least in part, by
      altering the natural history of HHV-8 infection.

PMID- 16414307
TI  - The epidermal growth factor stimulates sphingosine kinase-1 expression and
      activity in the human mammary carcinoma cell line MCF7.
AB  - Sphingosine 1-phosphate (S1P) the product of sphingosine kinase (SK) action plays
      an important role in various pathological conditions like inflammation and
      cancer. In this study, we show that in the human breast cancer cell line MCF7,
      epidermal growth factor (EGF) stimulates SK-1 activity in a biphasic manner with
      a first peak after 15 min and a second delayed activation occurring after 1 h up
      to 18 h and thereafter declining again. This delayed activation is accompanied by
      increased mRNA and protein expression of SK-1, but not SK-2. Mechanistically, the
      transcriptional upregulation is dependent on the classical mitogen-activated
      protein kinase, protein kinase C (PKC) and the phosphoinositide 3-kinase, since
      specific inhibitors of these enzymes all abolish the EGF-induced mRNA
      upregulation and activity of SK-1. Moreover, dexamethasone also suppressed EGF
      induced SK-1 mRNA expression and activity which is reversed by the glucocorticoid
      receptor antagonist RU486. To see whether EGF-induced upregulation of SK-1 is of
      relevance for tumor progression, we investigated two hallmarks of carcinogenesis,
      i.e., cell proliferation and migration. Stimulation of cells with EGF leads to
      enhanced [(3)H]thymidine incorporation into DNA and also to stimulated migration
      in a modified Boyden chamber assay. When cells are depleted of SK-1, but not SK
      2, by siRNA transfection or by dexamethasone treatment, EGF-induced proliferation
      and migration are drastically reduced. In summary, these data show that EGF
      causes an acute stimulation of SK-1 activity and, moreover, triggers a delayed SK
      activation which is due to increased gene transcription and de novo synthesis of
      SK-1, which in turn directs cells towards growth and increased motility. Thus,
      the sphingosine kinase-1 may represent a novel attractive target for cancer
      therapy.

PMID- 16414308
TI  - Basic surgical skills.
AB  - A team approach is essential to the practice of successful surgery. Good surgery
      begins before any incision is made with consideration of the type of equipment
      needed and the incision to be used to ensure optimum access. Although the
      repertoire of tools available to the surgeon has increased, the attainment of
      safe and efficient surgical technique still depends on a comprehensive knowledge
      of the basic surgical skills outlined in this chapter. These include proficiency
      in knot tying, instrument handling, suturing, haemostasis and tissue dissection.
      Surgery should 'flow', using the simplest and safest way to achieve the operative
      goal. As the duration of training shortens, the importance of teaching good
      surgical technique by example and direct supervision has never been greater.

PMID- 16414309
TI  - DNA vaccines increase immunogenicity of idiotypic tumor antigen by targeting
      novel fusion proteins to antigen-presenting cells.
AB  - Naked DNA vaccines have a number of advantages over conventional vaccines, but
      induce only weak immune responses. We have here investigated if this inadequacy
      may be overcome by inducing muscle to secrete fusion proteins with the ability to
      target antigen-presenting cells (APC). The novel targeted vaccines are homodimers
      with (i) two identical single-chain fragment variable (scFv) targeting units
      specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3
      dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes)
      from B cell cancers. After plasmid injection and electroporation of mouse muscle,
      secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC
      in draining lymph nodes for induction of T and B cell responses that protected
      mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell
      lymphoma (A20). Targeting to APC was essential for these effects. The results
      show that immunogenicity of plasmid DNA vaccines can be increased by inducing
      muscle to secrete proteins that target antigen to APC.

PMID- 16414310
TI  - Expression of TFAP2beta and TFAP2gamma genes in Xenopus laevis.
AB  - The embryonic expression patterns of two additional members of the transcription
      factor TFAP2 family in Xenopus laevis, TFAP2beta and TFAP2gamma, are described.
      Both genes share overlapping expression domains with the previously characterized
      TFAP2alpha in this species, although differences exist. All three genes are
      expressed in the neural crest (NC) region at late gastrula to early neurula
      stages. TFAP2alpha and TFAP2gamma are also expressed in outer, epidermal cells,
      while TFAP2beta is essentially NC-specific. All three are induced by Wnt/beta
      catenin -- BMP signals and all bind to a consensus TFAP2 recognition site from an
      epidermal keratin gene.

PMID- 16414311
TI  - Involvement of DNA mismatch repair in stationary-phase mutagenesis during
      prolonged starvation of Pseudomonas putida.
AB  - One of the popular ideas is that decline in methyl-directed mismatch repair (MMR)
      in carbon-starved bacteria might facilitate occurrence of stationary-phase
      mutations. We compared the frequency of accumulation of stationary-phase
      mutations in carbon-starved Pseudomonas putida wild-type and MMR-defective
      strains and found that knockout of MMR system increased significantly emergence
      of base substitutions in starving P. putida. At the same time, the appearance of
      1-bp deletion mutations was less affected by MMR in this bacterium. The spectrum
      of base substitution mutations which occurred in starving populations of P.
      putida wild-type strain was distinct from mutation spectrum identified in MMR
      defective strains. The spectrum of base substitutions differed also in this case
      when mutants emerged in starved populations of MutS or MutL-defective strains
      were comparatively analyzed. Based on our results we suppose that other
      mechanisms than malfunctioning of MMR system in resting cells might be considered
      to explain the accumulation of stationary-phase mutations in P. putida. To
      further characterize populations of P. putida starved on selective plates, we
      stained bacteria with LIVE/DEAD kit in situ on agar plates. We found that
      although the overall number of colony forming units (CFU) did not decline in long
      term-starved populations, these populations were very heterogeneous on the plates
      and contained many dead cells. Our results imply that slow growth of
      subpopulation of cells at the expenses of dead cells on selective plates might be
      important for the generation of stationary-phase mutations in P. putida.
      Additionally, the different survival patterns of P. putida on the same selective
      plates hint that competitive interactions taking place under conditions of
      prolonged starvation of microbial populations on semi-solid surfaces might be
      more complicated than previously assumed.

PMID- 16414312
TI  - Targeted gene repair activates Chk1 and Chk2 and stalls replication in corrected
      cells.
AB  - Oligonucleotides (ODNs) can direct the exchange of single nucleotides at specific
      sites in the mammalian genome. It is generally believed that the ODN aligns in
      homologous register with its complementary site in the target gene and provides a
      template for the endogenous repair machinery to alter the sequence of the gene.
      We have been studying the initial phase of the reaction with particular emphasis
      on the cellular events that occur when the oligonucleotide enters the cell. Our
      results show that, following introduction of the oligonucleotide, the DNA-damage
      response pathway is activated, evidenced by the presence of phosphorylated p53,
      Chk1 and Chk2, respectively. As a result, progression of some of these cells
      through the cell cycle is slowed and those bearing corrected genes all contain
      phosphorylated Chk1 and Chk2. In contrast, uncorrected cells contain much lower
      levels of these proteins in the activated state and pass through the cell cycle
      in a normal fashion. We suggest that gene repair directed by oligonucleotides
      activates a pathway that prevents corrected cells from proliferating in cell
      culture through the activation of Chk1 and Chk2. Our results impact the future
      use of gene repair for ex vivo gene therapy applications.

PMID- 16414313
TI  - Determination of quinalphos in blood and urine by direct solid-phase
      microextraction combined with gas chromatography-mass spectrometry.
AB  - A new method based on direct solid-phase microextraction (DI-SPME) followed by
      gas chromatography-mass spectrometry was developed for the purpose of determining
      quinalphos in blood and urine. Two types of coated fibre have been assayed and
      compared: carbowax/divinylbenzene (CW/DVB 65 microm) and polydimethylsiloxane
      (PDMS 100 microm). The main parameters affecting the SPME process such as
      temperature, salt addition, pH, stirring and adsorption/desorption time profiles
      were optimized to enhance the sensitivity of the procedure. The method was
      developed using only 100 microL of blood and urine. Limits of detection of the
      method for blood and urine matrices were, respectively, 10 and 2 ng/mL. Linearity
      was established over concentration ranges from 0.05 to 50 microg/mL for blood,
      and 0.01 to 50 microg/mL for urine, with regression coefficients ranging between
      0.9991 and 0.9999. Intra- and interday precision values were less than 13%, and
      accuracy was within +/-15% of the nominal concentration for all studied levels in
      both matrices. Absolute recoveries were 14 and 26% for blood and urine,
      respectively.

PMID- 16414314
TI  - A GC/MS validated method for the nanomolar range determination of succinylacetone
      in amniotic fluid and plasma: an analytical tool for tyrosinemia type I.
AB  - A sensitive and accurate stable isotope dilution GC/MS assay was developed and
      validated for the quantification of succinylacetone (SA) in plasma and amniotic
      fluid (AF). SA is pathognonomic for tyrosinemia type I, a genetic disorder caused
      by a reduced activity of fumarylacetoacetate hydrolase (FAH). In untreated
      patients, SA can easily be measured in plasma and urine because the expected
      concentrations are in the micromol/L range. Due to a founder effect, the province
      of Quebec has an unusually high prevalence of tyrosinemia type I, hence, the
      quantification of SA in AF or plasma of treated patients in the nmol/L range
      becomes very useful. The method utilizes 13C5-SA as an internal standard and a
      three-step sample treatment consisting of oximation, solvent extraction and TMCS
      derivatization. The assay was validated by recording the ion intensities of m/z
      620 for SA and m/z 625 for ISTD in order to demonstrate the precision of
      measurements, the linearity of the method, limit of quantification and detection
      (LOQ and LOD), specificity, accuracy, as well as metabolite stability. Values for
      the intra-day assays ranged from 0.2 to 3.2% while values for the inter-day
      assays ranged from 1.9 to 5.6% confirming that the method has good precision. A
      calibration plot using SA detected by GC/MS gave excellent linearity with a
      correlation coefficient of 0.999 over the injected concentration range of 5-2000
      nmol/L. LOQ and LOD were 3 and 1 nmol/L, respectively. The usefulness of this
      method was demonstrated by SA quantification in an AF sample of an affected fetus
      and in plasma of patients treated with NTBC. The results demonstrate that this
      novel GC/MS method may be a valuable tool for metabolic evaluation and clinical
      use.

PMID- 16414315
TI  - Protein depletion from blood plasma using a volatile buffer.
AB  - Removal of high abundance proteins is widely used in sample processing for
      proteomics studies of blood plasma. Immunoaffinity (IA) depletion is currently
      the most specific method for performing this step. Historically, IA depletion
      matrices have been designed to be used with inorganic buffers. However, the
      presence of salts in depleted samples presents a particular problem, and these
      must be removed in order to make samples compatible with post-depletion
      processing. Desalting (dialysis, ultrafiltration, size-exclusion, etc.) usually
      diminishes sample integrity due to labware associated losses. Moreover, these
      steps require additional labor, increasing the processing time and cost of
      analysis. In order to avoid these problems, we have developed an IA method using
      a volatile buffer that can be removed from depleted samples by lyophilization.
      This method allows the execution of reproducible and efficient depletion of blood
      plasma in a semi-automated manner.

PMID- 16414316
TI  - Protein stability and dynamics in the pressure-temperature plane.
AB  - The pressure-temperature stability diagram of proteins and the underlying
      assumptions of the elliptical shape of the diagram are discussed. Possible
      extensions, such as aggregation and fibril formation, are considered. An
      important experimental observation is the extreme pressure stability of the
      mature fibrils. Molecular origins of the diagram in terms of models of the
      partial molar volume of a protein focus on cavities and hydration. Changes in
      thermal expansivity, compressibility and heat capacity in terms of fluctuations
      of the enthalpy and volume change of the unfolding should also focus on these
      parameters. It is argued that the study of water-soluble polymers might further
      our understanding of the stability diagram. Whereas the role of water in protein
      behaviour is unquestioned, the role of cavities is less clear.

PMID- 16414317
TI  - Endoscopic ultrasonography in the diagnosis and management of portal
      hypertension. Where are we next?
AB  - Endoscopic ultrasonography has recently emerged as an accurate, non-invasive and
      reproducible alternative means of providing data for patients with portal
      hypertension. It is well established that endoscopic ultrasonography is more
      sensitive than endoscopy in the diagnosis of gastric varices. Dilated venous
      abnormalities outside the gastrooesophageal lumen, which cannot be diagnosed by
      endoscopy, are readily visible with endoscopic ultrasonography or miniature
      probes. Endoscopic ultrasonography is also useful to predict the risk of variceal
      recurrence and thus the risk of rebleeding after endotherapy which cannot be
      reliably predicted using endoscopy alone. The introduction of echo endoscopes
      equipped with Doppler facilities has allowed the sonographic visualisation of the
      vessels and the evaluation of vascular blood flow along with possible morphologic
      and haemodynamic changes after endoscopic or pharmacological therapy. However,
      despite its theoretical advantages, relative evidence suggests that in the
      clinical setting of portal hypertension, endoscopic ultrasonography remains an
      investigational tool with limited clinical applications.

PMID- 16414318
TI  - Why and how to invest in neonatal health.
AB  - The proportion of neonatal deaths in children has significantly increased,
      comprising at present almost 40% of all the nearly 11 million deaths of children
      under the age of five. In order to further reduce child mortality, substantial
      prompt attention to and reductions in neonatal mortality and morbidity are
      necessary. The reasons for insufficient investment in neonatal care are mostly
      based on incorrect assumptions about the importance, cost, and difficulty of
      tackling the issue. Further research is needed on the cost-effectiveness of
      neonatal interventions, but there is sufficient knowledge and evidence on the
      range, effect and cost-effectiveness of interventions to support significant
      increase in investments and broader programmatic implementation of available
      approaches. The continuum of care that follows the life-cycle is part of a high
      impact program delivery, supported by enabling environment, encompassing strong
      political commitment and strengthened comprehensive health system, from community
      level to clinical services. The international community needs to increase its
      funding and extend programs in close coordination with national health programs
      that are translated into partnerships at national and international level.

PMID- 16414319
TI  - Bone supplement: proceedings of ECTS/IBMS Geneva 2005-06-20.

PMID- 16414320
TI  - Proceedings from the NIH State-of-the-Science Conference on Management of
      Menopause-Related Symptoms, March 21-23, 2005, Bethesda, Maryland, USA.

PMID- 16414321
TI  - Defining the menopausal transition.
AB  - Menopause signifies the permanent cessation of ovarian function and the end of a
      woman's reproductive potential. A universal experience in women's aging, it is
      the culmination of some 50 years of reproductive aging--a process that unfolds as
      a continuum from birth through ovarian senescence to the menopausal transition
      and the postmenopause. The menopausal transition is known to play a major role in
      the etiology of many symptoms common in middle age and may contribute to chronic
      conditions and disorders of aging such as osteoporosis and cardiovascular
      diseases. However, the mechanisms underlying ovarian senescence and the
      occurrence of various short- and long-term biological and psychological sequelae
      are poorly understood. Progress in researching reproductive aging and the
      menopause has been impeded by the lack of a staging system based on meaningful,
      reliable, and objective criteria for staging reproductive aging and specifying
      menopause-related status. Current nomenclature is described and its limitations
      are discussed. Specifically, contemporary terminology lacks the sensitivity and
      specificity needed to operationally define a woman's reproductive status in the
      continuum of reproductive aging. A number of proposed staging systems are
      currently being evaluated for their suitability in identifying appropriate
      demarcations across the span of reproductive aging. Further research and a better
      understanding of the menopausal transition are necessary to establish the
      validity, practicality, and acceptability of these proposed staging systems.

PMID- 16414322
TI  - The menopausal transition.
AB  - Reproductive aging in women is related to the depletion of a fixed number of germ
      cells within the ovary. Prenatally, almost 50% of the maximal follicle pool is
      lost. Thereafter, atresia slows until women reach their early 40s, when total
      remaining follicle numbers reach a critical threshold. Atresia then becomes rapid
      once again, and women progress through the menopausal transition until they are
      left with essentially zero oocytes by a median age of 51.4 years. Fewer follicles
      result in a loss of inhibin B production and less physiologic "restraint" of
      follicle-stimulating hormone (FSH) secretion. Based on the responsiveness of the
      follicles present in any given month, a wide spectrum of hormonal patterns may
      occur. Women may alternate between inadequate folliculogenesis and more normal
      cycling. In the Study of Women's Health Across the Nation (SWAN), daily urine
      sampling was performed to assess hormonal dynamics. Older age and larger body
      size predicted aluteal cycles, and hormone excretion was lower in larger women.
      When annual hormones are examined, most of the decrease in estradiol and increase
      in FSH associated with menopause is found to occur during the late menopausal
      transition. There also is evidence that the central nervous system does not
      respond normally to estrogen and fails to produce preovulatory luteinizing
      hormone surges in women in the early transition. Clinically, it is important to
      appreciate that the entire reproductive system, not just the ovary, is undergoing
      change across the transition. Reproductive hormonal fluctuations may underlie
      some of the common symptomatology of the perimenopause.

PMID- 16414323
TI  - Symptoms during the perimenopause: prevalence, severity, trajectory, and
      significance in women's lives.
AB  - This article examines published evidence from longitudinal studies of the
      menopausal transition that address the following questions: (1) Which symptoms do
      women report during the perimenopause, and how prevalent are these symptoms as
      women traverse the menopausal transition? (2) How severe are symptoms and for how
      long do they persist? (3) To what do women attribute their symptoms, and do their
      attributions match findings from epidemiologic studies of community-based
      populations? (4) How significant are these symptoms in women's lives? Data from
      published longitudinal studies were examined for evidence bearing on each of
      these questions. Only vasomotor symptoms, vaginal dryness, and sleep disturbance
      symptoms varied in prevalence significantly across menopausal transition stages
      and postmenopause in >1 population studied. A minority of women report severe
      symptoms. Given the limited follow-up data available, it is unclear how long
      symptoms persist after menopause. Women attribute their symptoms to a variety of
      biologic and psychosocial factors, and their attributions correspond well to
      those correlates identified in epidemiologic studies of community-based
      populations. The significance of symptoms for women's lives remains uncertain.
      The impact of symptoms during the perimenopause on well-being, role performance,
      adaptation to demands of daily living, and quality of life warrants additional
      study. The appraisal of the consequences of perimenopausal symptoms by women from
      different ethnic groups will be enhanced significantly as a result of the Study
      of Women's Health Across the Nation (SWAN) and other studies in progress.

PMID- 16414324
TI  - Does the menopausal transition affect health-related quality of life?
AB  - We address whether the menopausal transition affects health-related quality of
      life (HRQOL). To do this, we review how HRQOL is defined and measured, present
      HRQOL findings from the large, population-based studies of menopause, and
      identify key gaps in knowledge. HRQOL is defined as the value assigned to
      duration of life as modified by impairments, functional states, perceptions, and
      social opportunities that are influenced by disease, injury, treatment, or
      policy. The specific domains of HRQOL include resilience or the capacity to
      respond to stress, health perceptions, physical functioning, and symptoms. The
      majority of menopause studies have operationalized HRQOL as frequency and
      severity of symptoms. Taken together, the findings from 12 cross-sectional
      reports and 3 longitudinal studies suggest that the perimenopause is associated
      with higher levels of somatic symptoms. It is unclear whether the perimenopause
      is related to other domains of HRQOL. Only 1 longitudinal study reported an
      association between reduced physical functioning and perimenopause. Studies
      typically compare premenopausal women with women of other menopausal transition
      status separately, thereby not addressing the question of further change in HRQOL
      after the cessation of menses. There is a clear need for understanding the
      effects of the menopause beyond the domain of symptoms and to consider whether
      some domains of HRQOL may improve.

PMID- 16414325
TI  - A universal menopausal syndrome?
AB  - A variety of symptoms are reported frequently as being part of a menopausal
      syndrome. These include hot flashes, night sweats, menstrual irregularities,
      vaginal dryness, depression, nervous tension, palpitations, headaches, insomnia,
      lack of energy, difficulty concentrating, and dizzy spells. The question of
      whether and how symptoms occur together is important for women who want to know
      which symptoms can be attributed to menopause and which to aging generally or to
      other physical or psychosocial factors. To address this question, the present
      article examines the following avenues of research: (1) the clustering or
      grouping of symptoms; (2) the temporal association of different symptoms with
      stages of the menopausal transition; (3) the consistency of symptom reporting
      across cultures, race, and ethnicity; and (4) the consistency of risk factors for
      symptoms. Results of the factor analysis studies do not support a single syndrome
      consisting of menopausal and psychological or somatic symptoms. The prevalence of
      symptom reporting across the transition also argues against a menopausal syndrome
      because vasomotor symptoms follow a unique pattern that differs from that of
      other symptoms. Cross-cultural differences suggest that symptom reporting is not
      universal. Finally, although there is some overlap in risk factors for symptoms,
      menopausal status is more consistently related to vasomotor symptoms than to
      psychological or physical ones. Results of these investigations all argue against
      a universal menopausal syndrome. Future research should focus on how symptoms are
      interrelated, what factors are uniquely related to vasomotor symptoms, and
      identifying whether there is a subgroup of women who are more likely to report
      symptoms.

PMID- 16414326
TI  - Genitourinary symptoms in the menopausal transition.
AB  - Irregular uterine bleeding is a common symptom among women in the menopausal
      transition. Women commonly transition from having regular cycles to having
      irregular cycles before the final menstrual period. In late perimenopause,
      anovulation becomes more common, leading to skipped menstrual cycles. Low-dose
      oral contraceptive pills are effective in decreasing the amount of menstrual
      blood loss and improving menstrual cycle regularity. It is unclear whether
      menorrhagia is associated with normal perimenopausal hormonal changes. Studies to
      date have failed to correlate menorrhagia with hormonal levels and pathology
      within the uterus. Because of the common association between uterine pathology
      and menorrhagia, this is an important area for future studies. Vaginal dryness is
      a common symptom, particularly in late perimenopause. The association between
      vaginal dryness and low estrogen levels is clear. Estrogen-based hormone
      replacement therapy is effective in treating this symptom. Locally released
      estrogen therapy may be preferred over systemic therapy because of lower systemic
      estradiol levels, reduced side effects, and high efficacy. The long-term safety
      of these products, particularly in women with a history of breast cancer,
      requires more study. The prevalence of incontinence increases as women age, but
      it is unclear whether the menopausal transition is an independent risk factor.
      Incontinence is a frequent complaint among women in the menopausal transition. In
      postmenopausal women, hormone therapy (HT) appears to be ineffective in
      preventing or improving the symptoms of incontinence. Further study of HT,
      including locally applied estrogens for the common symptom of incontinence, are
      needed in women in the menopausal transition.

PMID- 16414327
TI  - Mood, depression, and reproductive hormones in the menopausal transition.
AB  - This article focuses on a review of evidence related to the following 3
      questions: (1) Does depression appear during the menopausal transition? (2) What
      factors influence the risk for depression during the menopausal transition? (3)
      Do age-related alterations in ovarian hormone secretion contribute to the
      development of depression in some middle-aged women? A brief background is
      provided on the importance of depressive disorders. Methodologic issues that have
      compromised previous studies investigating the possible relation between the
      menopausal transition and depression are discussed. Evidence is presented that
      suggests a relation between the perimenopause (the interval between the early
      menopausal transition and 1 year after the last menses), but not the
      postmenopause, and the onset of depressive illness. Finally, studies are reviewed
      that suggest an association between alterations in ovarian function and
      depression, including several randomized placebo-controlled trials examining the
      antidepressant efficacy of estradiol in depressed perimenopausal and
      postmenopausal women.

PMID- 16414328
TI  - Sexuality.
AB  - This article reviews changes in sexual function in middle-aged women and
      discusses how these changes relate to aging, hormone alterations, and
      psychosocial and physical factors. A Medline search of population-based studies
      that measured sexual function, menopausal status and/or hormone levels was
      conducted. Longitudinal findings are from the Melbourne Women's Midlife Health
      Project, a population-based sample of 438 Australian-born white women, aged 45 to
      55 years, who were menstruating at baseline. Annual assessments included hormone
      levels and the Short Personal Experiences Questionnaire. Few of the population
      based studies of the menopausal transition measured sexual function or hormones.
      Aging and the length of the woman's relationship with her partner are associated
      with decline in sexual function. An additional decrement in sexual function
      occurs in midlife associated with menopause. Findings from the Melbourne Women's
      Midlife Health Project using structural equation modeling, found the most
      important factors influencing a woman's sexual function are prior level of sexual
      function; losing or gaining a sexual partner; feelings toward a partner; and
      estradiol level. When psychosocial and lifestyle status were added to the model,
      mood was the only additional variable affecting sexual function. There is a
      decline in all aspects of female sexual function with age. A further incremental
      decline in most aspects of sexual function occurs as women pass through the
      menopausal transition and is related to decreasing estradiol levels. Other
      factors such as prior sexual function and partner issues have larger effects on
      women's sexual function than do hormonal factors.

PMID- 16414329
TI  - Estrogens and progestins: background and history, trends in use, and guidelines
      and regimens approved by the US Food and Drug Administration.
AB  - The US Food and Drug Administration (FDA) approved marketing of
      diethylstilbestrol in 1941 and conjugated equine estrogens (CEE) in 1942 for
      treatment of menopausal symptoms. Estrogen sales doubled and tripled in the mid
      1960s to mid-1970s, until 1975, when reports of increased endometrial cancer in
      estrogen users resulted in a dramatic decline. Estrogen use increased again, with
      evidence of protective effects of progestins on estrogen-induced endometrial
      changes, combined with a 1982 report that Premarin (conjugated estrogen tablets;
      Wyeth Pharmaceuticals, Philadelphia, PA) retained bone mass and a 1984 National
      Institutes of Health (NIH) Consensus Conference on Osteoporosis statement that
      estrogens were the most effective means for preventing bone loss. Despite
      conflicting reports in 1985 regarding the relation between estrogens and coronary
      heart disease (CHD), many published observations of reduced CHD risk in estrogen
      users--reinforced by clinical trial findings in 1995 of favorable lipoprotein
      changes in women assigned to CEE with or without a progestin--promoted increased
      use through the 1990s. By 2001, approximately 15 million US women were using
      estrogen therapy, with or without progestins. The 2002 Women's Health Initiative
      (WHI) report of greater harm than benefit of combined CEE plus a progestin
      resulted in a precipitous decrease in estrogen and progestin use and a serious
      reevaluation of menopausal hormone therapy, as well as increased interest in
      alternative approaches to managing menopausal symptoms, including use of
      "bioidentical" hormones. FDA guidelines regarding treatment indications for
      vasomotor symptoms, vaginal atrophy, and osteoporosis prevention have resulted in
      approval of several estrogen (and progestin) formulations, doses, and routes of
      administration, thereby providing many options for women who seek conventional
      therapy.

PMID- 16414330
TI  - Vasomotor symptom relief versus unwanted effects: role of estrogen dosage.
AB  - Recent clinical trials show that low-dose estrogen reduces the number of moderate
      to severe vasomotor episodes by 65%. This reduction is about midway between the
      35% to 40% reduction observed with placebo and the 75% to 80% reduction observed
      with standard dosage. Compared with standard dosages whose effects are
      substantial by 4 weeks, relief with lower dosages is not maximal until 8 to 12
      weeks. Women using lower dosages of estrogen experience 50% lower rates of
      irregular bleeding or breast tenderness compared with individuals taking standard
      dosages. Despite several lower dosage hormone therapy (HT) formulations being
      approved by the US Food and Drug Administration (FDA) and brought to market,
      their uptake by healthcare providers has been slow. Most women who have continued
      HT after reports of the Women's Health Initiative (WHI) were published take
      estrogen at the standard dosage; only a minority of these individuals report
      receiving guidance about switching to a lower dosage. The purpose of this review
      is to summarize the clinical trial data showing, on one hand, effects of various
      dosages of estrogen on vasomotor symptoms and, on the other hand, the effects of
      these same doses on troublesome adverse events, particularly vaginal bleeding or
      breast tenderness. It is time to reconsider the current estrogen dosage
      recommendation on the basis of symptom benefit versus symptom nuisance.
      Furthermore, healthcare providers need to learn how and when to prescribe lower
      dosages of HT to optimize patient acceptance and continuation.

PMID- 16414331
TI  - Estrogen with and without progestin: benefits and risks of short-term use.
AB  - Estrogen therapy has been well established as an effective treatment for relief
      of vasomotor symptoms. In light of recent evidence from large randomized trials
      showing serious risks associated with use of estrogen treatment, current
      recommendations for hormone therapy emphasize using the lowest effective dose for
      the shortest possible time. The purpose of this review is to examine what has
      been learned from the Women's Health Initiative (WHI) Hormone Trials and other
      studies about the short-term risks and benefits of estrogen use. A second purpose
      is to examine whether short-term risks differ for women most likely to use
      hormone treatment, including individuals with vasomotor symptoms; women in their
      50s; and women, with and without intact ovaries, who have had a hysterectomy.
      During the first 1 to 2 years of use of conjugated equine estrogens alone (E
      alone) or combined with medroxyprogesterone acetate (E + P), women experience an
      elevated risk of coronary heart disease, stroke, and deep vein thrombosis or
      pulmonary embolism. The magnitude of risk is greater for E + P than for E-alone.
      Fracture risk is not reduced with 1 to 2 years of use, but a fracture benefit is
      seen within 5 years of use. Increased risk of breast cancer does not appear until
      after 4 to 5 years of E + P use and was not increased with E-alone use after < or
      =7 years of treatment. This pattern of risks and benefits is generally similar
      for women with vasomotor symptoms, women in their 50s, and women, with and
      without > or =1 intact ovary, who have had a hysterectomy.

PMID- 16414332
TI  - Therapeutic effects of progestins, androgens, and tibolone for menopausal
      symptoms.
AB  - Therapeutic strategies using progestins, androgens, and synthetic steroids such
      as tibolone are based on the understanding that estrogen, progesterone, and
      androgen receptors are localized to reproductive target tissues, brain, and bone.
      Unfortunately, these sex steroid receptors are widely distributed and localized
      to other tissues, often resulting in unintended effects. Progestins at high doses
      have been shown to be effective at reducing hot flashes by approximately 80% to
      90%. Side effects include weight gain, mastalgia, fluid retention, vaginal
      discharge, and dry mouth. Dehydroepiandrosterone (DHEA), an adrenal-derived
      androgen, can be considered a prohormone that is peripherally converted to more
      potent androgens and estrogens. In studies with small numbers of subjects, DHEA
      has been reported to reduce vasomotor symptoms, increase sexual arousal, and
      improve cognitive performance. With regard to use of other androgens, there are
      no current testosterone preparations approved by the US Food and Drug
      Administration (FDA) for use in menopausal women. In phase 3 trials, a
      testosterone transdermal matrix patch has been shown to be effective in treatment
      of hypoactive sexual desire disorder in menopausal women on estrogen therapy.
      Tibolone, a synthetic steroid with estrogenic, androgenic, and progestational
      properties has been shown to be effective in the treatment of vasomotor symptoms
      and in preserving bone density, and it may provide positive effects on sexual
      function. The beneficial effects of these compounds in the menopausal woman for
      treatment of vasomotor symptoms, general well-being, cognitive deficits, bone
      loss, mood disorders, and sexual function are discussed. The overall clinical
      trial evidence for benefits and side effects also is presented.

PMID- 16414333
TI  - Diagnosis and management of mood disorders during the menopausal transition.
AB  - Recent census data indicate that, in the United States, an increasing number of
      women--almost 1.5 million each year--are reaching menopause. The menopausal
      transition is marked by intense hormonal fluctuations, and may be accompanied by
      vasomotor complaints, sleep disturbances, changes in sexual function, and
      increased risk for osteoporosis and cardiovascular disease. In addition, there is
      evidence of increased risk for developing depression, even among women who never
      experienced depressive symptoms before. Thus depression during the perimenopause
      may have a substantial impact on personal, family, and professional spheres of
      life. A challenge to clinicians and health professionals lies in the
      identification of the most tolerable treatments to manage depression and improve
      quality of life in an aging population. Any treatment strategy should take into
      account not only the spectrum of side effects that may complicate treatment but
      also other menopause-related factors (e.g., vasomotor symptoms, psychosocial
      stressors) that may modulate risk for the development of mood disturbance. This
      article reviews the current literature on the prevalence and risk factors
      associated with depression during the menopausal transition. The benefits and
      risks of using hormonal and nonhormonal strategies for the management of
      depression and other menopause-related somatic symptoms are critically reviewed.

PMID- 16414334
TI  - Menopause: a review of botanical dietary supplements.
AB  - Since the release of the Women's Health Initiative (WHI) findings, an increasing
      number of dietary supplement products specifically targeting women in menopause
      have appeared in the American marketplace. This growth highlights the need for a
      critical evaluation of the tolerability and effectiveness of these products. The
      purpose of this article is to assess the evidence for safety and benefit of
      botanical monopreparations used for relief of menopause-related symptoms. The
      Cochrane Library and Medline databases were searched from January 1966 to October
      2004, using a detailed list of terms related to botanicals and menopausal
      symptoms. Studies were considered eligible (1) if they were controlled trials of
      a botanical monopreparation administered orally for a minimum of 6 weeks to
      perimenopausal or postmenopausal women with hot flashes and (2) if they included
      a placebo or comparative treatment arm. Topical preparations, botanical
      combinations, and dietary interventions, such as soy food or protein, were not
      included. No language restrictions were imposed on the search. A total of 19
      studies met the inclusion criteria. The majority of studies indicate that extract
      of black cohosh (Actaea racemosa L.) improves menopause-related symptoms;
      however, methodologic shortcomings in the trials were identified. To date, 4 case
      reports of possible hepatotoxicity have been published, although previous safety
      reviews suggest that black cohosh is well tolerated and that adverse events are
      rare when it is used appropriately. The results of 6 clinical studies on soy
      (Glycine max L.) isoflavone extracts are mixed. Moreover, the composition and
      dose of soy supplements varies widely across studies, making comparisons and
      definitive conclusions difficult. One study challenged the long-term safety of
      high-dose soy isoflavone extract (150 mg/day for 5 years) on the uterine
      endometrium. Clinical data from 5 controlled trials assessing the efficacy of
      semipurified isoflavone red clover (Trifolium pratense L.) leaf extracts to
      reduce hot flash frequency and severity or to relieve symptoms associated with
      the domains of the Greene Menopausal Symptom Scale are contradictory. The largest
      study showed no benefit for reducing symptoms associated with menopause for 2
      different red clover isoflavone products compared with placebo. No significant
      adverse events have been reported in the literature. Single clinical trials do
      not support the use of dong quai (Angelica sinensis L.), ginseng (Panax ginseng
      C.A. Mey), or evening primrose seed oil (Oenothera biennis L.) for improving
      menopausal symptoms. We conclude that black cohosh extracts appear to ease
      menopausal symptoms; ongoing studies funded by the National Institutes of Health
      (NIH) will provide more definitive safety and efficacy data. Soy isoflavone
      extracts appear to have minimal to no effect, although definitive conclusions are
      difficult given the wide variation in product composition and dose. Long-term
      safety of higher dosage (150 mg/day) soy isoflavone extracts is uncertain.
      Semipurified isoflavone red clover leaf extracts have minimal to no effect in
      reducing menopausal symptoms. Dong quai, ginseng extract, and evening primrose
      seed oil appear to be ineffective in ameliorating menopausal symptoms at the
      dosages and in the preparations used in these studies.

PMID- 16414335
TI  - Other complementary and alternative medicine modalities: acupuncture, magnets,
      reflexology, and homeopathy.
AB  - We sought to evaluate evidence for the benefits and risks of acupuncture,
      magnets, reflexology, and homeopathy for menopause-related symptoms. Search
      strategies included electronic searches of online databases (PubMed, PsycINFO,
      Medline), direct searches of target journals, and citation-index searches. A
      total of 12 intervention studies were identified for review. Complementary and
      alternative medicine (CAM) treatments resulted in few side effects. The design,
      study populations, and findings across acupuncture studies varied. In
      uncontrolled studies, acupuncture improved subjective measures of hot flash
      frequency and vasomotor, somatic, physical, and psychological symptoms; however,
      improvements were not consistent. Controlled studies of acupuncture yielded even
      less consistent findings. Overall, controlled studies of acupuncture did not
      reliably improve hot flashes, sleep disturbances, or mood when compared with
      nonspecific acupuncture, estrogen therapy, or superficial needling. Homeopathy
      significantly improved subjective measures of hot flash frequency and severity,
      mood, fatigue, and anxiety in uncontrolled, open-label studies. Controlled
      studies of magnets and reflexology failed to demonstrate any increased benefit of
      treatment over placebo. There is a need for additional investigations of
      acupuncture and homeopathy for the treatment of hot flashes and other menopausal
      symptoms. However, existing evidence does not indicate a beneficial effect of
      magnets or reflexology in the treatment of hot flashes and other menopausal
      symptoms. Understanding whether, for whom, and how these interventions work is
      crucial to building the evidence base needed to evaluate any potential for these
      CAM therapies in the management of menopause-related symptoms.

PMID- 16414336
TI  - Centrally active nonhormonal hot flash therapies.
AB  - Given the problems associated with hormonal therapy, and the prominent problem of
      hot flashes in menopausal women, there is a need for nonhormonal agents to
      alleviate hot flashes. Several compounds that appear to act on the central
      nervous system have been investigated. Potential mechanisms for their effects on
      hot flashes have been described. Bellergal (no longer available on the US market,
      where it was known as Bellergal-S), a combination preparation sedative that
      consists of low-dose phenobarbital, ergotamine tartrate, and levorotatory
      alkaloids of belladonna, is an old agent that was popular approximately 20 years
      ago; however, there is limited suggestion of efficacy for this agent. Clonidine,
      an older antihypertensive drug, is another centrally active agent that has been
      studied. Randomized trials have demonstrated that it clearly works for reducing
      hot flashes, but the magnitude of efficacy is somewhat limited. Toxicity from
      this agent limits its utility in the clinic. Methyldopa is another centrally
      active agent that has been studied but to a more limited degree. It appears to
      have minimal efficacy and too much toxicity to make it clinically useful.
      Anecdotal observations from a number of sources suggested that newer
      antidepressants can alleviate hot flashes. This led to pilot trials of
      venlafaxine and paroxetine, with results suggesting benefit from both drugs.
      Subsequently, randomized, placebo-controlled, double-blind clinical trials of
      venlafaxine, paroxetine, and fluoxetine were conducted. All 3 of these clinical
      trials demonstrated statistically significant reductions in hot flashes with
      these newer antidepressants compared with placebo. Pilot trials of citalopram and
      mirtazapine, 2 other newer antidepressants, have also suggested efficacy.
      Toxicity evaluations have suggested that these agents are, again, well tolerated
      by the majority of patients. A recent trial, however, was unable to demonstrate
      any benefit for fluoxetine or citalopram over a placebo. Anecdotal observations
      also suggested that gabapentin was helpful for alleviating hot flashes. This led
      to pilot trials that again suggested efficacy. Subsequently, 2 large placebo
      controlled, randomized, double-blind clinical trials were conducted. Both of
      these demonstrated statistically significant efficacy for gabapentin compared
      with a placebo. This drug is relatively well tolerated by most patients. Thus,
      centrally active nonhormonal agents clearly do decrease hot flashes in women. The
      most efficacious and clinically appropriate agents for use are newer
      antidepressants and gabapentin. Continued evaluation of the efficacy and toxicity
      of these agents is ongoing.

PMID- 16414337
TI  - Hot flashes: behavioral treatments, mechanisms, and relation to sleep.
AB  - Hot flashes are the most common symptom of the climacteric and occur in about 75%
      of perimenopausal and postmenopausal women in Western societies. Although hot
      flashes accompany the withdrawal of estrogen at menopause, the decline in
      estrogen levels is not sufficient to explain their occurrence. Elevated
      sympathetic activation acting through central alpha(2)-adrenergic receptors
      contributes to the initiation of hot flashes, possibly by narrowing the
      thermoneutral zone in symptomatic women. Hot flashes are then triggered by small
      elevations in core body temperature acting within this narrowed zone. A
      relaxation-based method, paced respiration, has been shown in 3 controlled
      investigations to significantly reduce objectively measured hot flash occurrence
      by about 50% with no adverse effects. In 6 studies of physical exercise, however,
      investigators did not find positive effects on hot flashes, possibly because
      exercise raises core body temperature, thereby triggering hot flashes. Although
      many epidemiologic studies have found increased reports of sleep disturbance
      during the menopausal transition, recent laboratory investigations have not found
      this effect, nor have they found that hot flashes produce disturbed sleep.
      Therefore, sleep complaints in women at midlife should not routinely be
      attributed to hot flashes or to menopause.

PMID- 16414338
TI  - Bilateral oophorectomy and premature menopause.
AB  - The ovary is a complex metabolic organ. The follicles produce both androgens and
      estrogens, whereas the stromal tissue synthesizes androgens only. When menopause
      occurs, both androgen and estrogen levels decrease. The postmenopausal ovary
      remains a source of endogenous androgens that are converted to estrogen. The
      consequences of premature removal of the ovaries are not well known. The risks
      and benefits of menopausal hormone therapy (HT) in women with premature menopause
      have not been studied. Women who have had surgical menopause experience more
      severe symptoms and will need to stop estrogen therapy at some point in their
      lives. Intense symptoms such as hot flashes, night sweats, and insomnia will
      redevelop, so women should be given informed consent about the need for long-term
      use of HT and the greater difficulty in discontinuing therapy.

PMID- 16414339
TI  - Breast cancer, menopause, and long-term survivorship: critical issues for the
      21st century.
AB  - Breast cancer accounts for 33% of all incident cancers in women in North America,
      and there are an estimated >2 million breast cancer survivors in the United
      States today. Ovarian hormones are intimately involved in the initiation and
      promotion of breast cancer development, with targeted endocrine therapies being
      the most widely used as anticancer treatment. It is not surprising that these
      treatments frequently cause persistent menopausal symptoms in breast cancer
      survivors. In addition, adjuvant chemotherapy often induces premature menopause
      in younger patients with breast cancer. Some women at high risk for the
      development of breast cancer (e.g., precancerous breast disease, carriers of
      deleterious hereditary predisposition genes) experience vasomotor symptoms as a
      result of tamoxifen therapy or preventive oophorectomy. Clinical management of
      menopausal symptoms in these settings is complicated by the relative prohibition
      of hormonal therapies and the fact that breast cancer-directed therapies often
      exacerbate these menopausal symptoms. Thus, this special population of women
      requires unique management strategies and deserves separate consideration.

PMID- 16414340
TI  - Strategies and issues for managing menopause-related symptoms in diverse
      populations: ethnic and racial diversity.
AB  - Menopause is a naturally occurring "equal opportunity" event that every woman who
      lives beyond the age of approximately 52 years will experience. During the next
      20 years, approximately 3.5 million African American women, 2 million Latinas,
      and 1 million Asian American women will enter the menopause. How a woman
      approaches the menopausal transition depends on a number of factors, from
      educational level to socioeconomic status; health-related factors, including
      stress; and marital status. Increasingly, the roles of race and ethnicity, as
      they relate to menopausal symptoms, are being explored. Understanding
      similarities and differences among women of color in perceptions, attitudes, and
      expectations surrounding the menopause can help provide culturally appropriate
      care and promote lifestyles that may decrease symptoms and increase quality of
      life. For example, minority women are usually the gatekeepers for healthcare for
      themselves and their families and have a highly developed social support network,
      often including extended family, a church community, and involvement in sororal
      or social organizations. In the future, research on menopausal symptoms among
      women of different racial/ethnic groups should focus on exploring in greater
      detail the effect of dietary factors and body mass index, additional evaluation
      of pituitary sensitivity, and use of complementary and alternative medicines in
      symptom management, with a better understanding of the risks and benefits of such
      therapies.

PMID- 16414342
TI  - The impact of risk status, preexisting morbidity, and polypharmacy on treatment
      decisions concerning menopausal symptoms.
AB  - Because each menopausal treatment has a unique benefit-risk profile, deciding
      whether menopausal hormone therapy (HT) or another menopausal treatment is
      appropriate for an individual requires assessing the risks and benefits of each
      treatment as well as determining the patient's risk factors, comorbidities, and
      current medications. Simple summary metrics for assessing net treatment effects
      on multiple outcomes, such as the Women's Health Initiative's (WHI) global index,
      are not necessarily generalizable beyond the study population in which they were
      derived. However, trial evidence can be translated to individual decisions by
      transforming relative risks into absolute risks. The validity of generalizing
      relative risks found in clinical trials to groups with differing baseline risks
      depends on the homogeneity of relative risks across various risk strata. Subgroup
      analyses from the major clinical studies of HT found its relative risks for
      cardiovascular disease, hip fracture, breast cancer, colorectal cancer, and
      ovarian cancer to be relatively uniform across strata defined by age,
      race/ethnicity, antecedent risk status, or prior disease. The number of
      significant subgroup findings in these studies tended to match the number
      expected by chance alone. However, data are limited for many subgroups,
      especially those with comorbidities. Strata defined by the concurrent use of
      drugs that can interact with HT are not expected to be homogeneous, yet data on
      drug interactions are limited. More data are needed about the effects of
      menopausal treatments in diverse populations, and more attention is needed to
      translate this evidence into clinical practice and to develop tools to support
      informed decision making.

PMID- 16414341
TI  - Lifestyle factors: are they related to vasomotor symptoms and do they modify the
      effectiveness or side effects of hormone therapy?
AB  - This article reviews and summarizes published literature in order to address the
      following questions: (1) Are lifestyle factors (alcohol use, cigarette exposure,
      and physical activity) and body mass index (BMI) related to the occurrence of
      vasomotor symptoms in perimenopausal and postmenopausal women? (2) Do lifestyle
      factors or BMI modify the effectiveness or side effects of menopausal hormone
      therapy (HT)? Information was culled from a nonstructured review of English
      language literature. Low levels of alcohol consumption (< or =1 drink per day for
      women) do not have a measurable effect on occurrence of vasomotor symptoms;
      whether greater amounts of alcohol intake would promote vasomotor symptoms cannot
      be addressed by available literature. Most published studies report that active
      cigarette smoking is positively associated with vasomotor symptoms. However, a
      large study found that passive (but not active) smoking (i.e., secondhand smoke
      exposure) was related to vasomotor symptoms. Studies to date do not support a
      relation between physical activity and vasomotor symptoms. However, rates of
      vasomotor symptom reporting were low in these studies, potentially limiting the
      ability to detect an effect of physical activity. Greater BMI is a risk factor
      for more vasomotor symptom reporting. The scarcity of data that directly address
      whether lifestyle factors or BMI modify the effects of HT precludes a substantive
      response to this question at present. Available literature suggests that smoking
      and greater body weight are risk factors for vasomotor symptoms; women with
      vasomotor symptoms who smoke may benefit from smoking cessation, and women who
      are heavier than ideal body weight may benefit from weight reduction. Whether
      certain behaviors or BMI raise or lower the risks or benefits of HT remains
      largely unknown and should be the focus of future research.

PMID- 16414343
TI  - Discontinuation of postmenopausal hormone therapy.
AB  - Current guidelines recommend that postmenopausal hormone therapy (HT) be used
      primarily for treatment of vasomotor and urogenital symptoms associated with the
      menopausal transition and that women use the lowest effective dose for the
      shortest time necessary. Vasomotor symptoms improve or resolve spontaneously
      within a few months to a few years of onset in the majority of women, suggesting
      that most women should be able to discontinue HT within a few years of starting
      treatment. Approximately 75% of women who try to stop are able to stop HT without
      major difficulty. However, some women who would like to stop HT are unable to do
      so, mainly owing to the development of vasomotor symptoms. Troublesome symptoms
      associated with stopping HT appear to be more common among women who start HT for
      treatment of symptoms, but they also are reported by women who started HT for
      other reasons, such as prevention of osteoporosis. Unfortunately, little
      information is available to guide physicians in helping women who have difficulty
      stopping HT. Many clinicians recommend slowly tapering HT or adding another drug
      for treatment of hot flashes, but the effectiveness of these approaches has not
      been evaluated. For women who cannot tolerate even a slow taper, the value of
      symptom relief likely outweighs any increased risks due to HT use.

PMID- 16414344
TI  - Research opportunities for reducing the burden of menopause-related symptoms.
AB  - The National Institutes of Health (NIH) State-of-the-Science (SoS) Conference on
      the Management of Menopause-Related Symptoms identified a number of important
      gaps in our understanding of the natural history of the menopausal transition and
      the etiology and course of menopause-related symptoms. Updated information is
      needed from prospective studies of reproductive aging in diverse populations of
      women, especially of younger women in their mid reproductive years, to better
      understand the underlying biology of ovarian aging as well as the etiology of
      conditions leading to premature spontaneous or surgical menopause. To facilitate
      this goal, a number of methodologic issues must be addressed, including the
      development of (1) consensus definitions of menopause-related terms and stages,
      and (2) standard measures and methods for assessing progression through the
      menopausal transition and related symptoms and outcomes. Estrogen therapy is
      highly efficacious in relieving menopausal symptoms and was the treatment of
      choice until 2002, when findings of unexpected harm from the Women's Health
      Initiative (WHI) were published. Consequently, there has been a burgeoning
      interest in a number of botanical products as well as other complementary and
      alternative medicine strategies, such as acupuncture, magnets, homeopathy, and
      behavioral regimens. However the benefits of most of these strategies are either
      very limited or equivocal, and related safety issues are poorly understood.
      Future research is needed to identify new efficacious strategies, to understand
      side effects and safety issues, and to provide new options to women who are
      burdened by bothersome menopause-related symptoms.

PMID- 16414346
TI  - CYP3C1, the first member of a new cytochrome P450 subfamily found in zebrafish
      (Danio rerio).
AB  - We report a new cytochrome P450 (CYP) subfamily CYP3C and the cloning through PCR
      from zebrafish (Danio rerio) of the first member, CYP3C1. The CYP3C1 gene is on
      Chromosome 3 with 13 ORF exons encoding a 505 amino acid protein which has 44-54%
      identities with mammalian and teleost CYP3A and CYP3B forms. As evidenced by
      spectral analysis, the CYP3C1 protein heterologously expressed in yeast is
      functional. In silico analysis identified, on the same region of the chromosome,
      three more genes encoding CYP3C1-like proteins that formed a clade with CYP3C1 in
      a phylogenetic tree. Using RT-PCR, the CYP3C1 mRNA was detected in 1-6dpf
      embryo/larvae and in adult fish liver and seven extrahepatic tissues. Whole-mount
      in situ hybridization using a riboprobe demonstrated expression in the brain
      during 12-120 hpf. At the 120 hpf larval stage, CYP3C1 mRNA was also detected in
      the pharynx and gastrointestinal tract. TCDD, dexamethasone, and rifampicin,
      which up-regulated CYP3A65 mRNA in zebrafish larvae, did not alter the CYP3C1
      transcript levels suggesting regulatory differences between CYP3A and CYP3C
      enzymes in this species.

PMID- 16414345
TI  - The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in
      motor skill learning.
AB  - Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti
      proliferative activity in peripheral tissues. Our previous study identified Tob
      as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin,
      X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing,
      B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is
      a multifunctional protein involved in hippocampus-dependent learning and memory,
      Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the
      central nervous system is engaged in acquisition of motor skill. Tob has a
      relatively high expression in the cerebellum. Tob expression is up-regulated in
      the cerebellum after rats receive training on a rotarod-running task. Rats
      infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a
      severe deficit in running on a rotating rod or walking across a horizontally
      elevated beam.

PMID- 16414347
TI  - Timing of Ca2+ response in pancreatic beta-cells is related to mitochondrial
      mass.
AB  - The timing and magnitude of calcium response are cell-specific in individual beta
      cells. This may indicate that the cells have different roles in the intact islet.
      It is unknown what mechanisms determine these characteristics. We previously
      found that the mechanisms setting cell-specific response timing are disturbed in
      beta-cells from hyperglycemic mice and one of the causes is likely to be an
      altered mitochondrial metabolism. Mitochondria play a key role in the control of
      nutrient-induced insulin secretion. Here, we used confocal microscopy with the
      fluorescent probe MitoTracker Red CMXRos and Fluo-3 to study how the amount of
      active mitochondria is related to the lag-time and the magnitude of calcium
      response to 20mM glucose in isolated beta-cells and in cells within intact lean
      and ob/ob mouse islets. Results show that the mitochondrial mass is inversely
      correlated with the lag-times for calcium response both in lean and ob/ob mouse
      beta-cells (r=-0.73 and r=-0.43, respectively, P<0.05). Thus, the state of
      mitochondria may determine the timing of calcium response.

PMID- 16414348
TI  - Amino acid substitutions around the chromophore of the chromoprotein Rtms5
      influence polypeptide cleavage.
AB  - Extension of the conjugated pi-system of many all-protein chromophores with an
      acylimine bond is the basis for their red-shifted optical properties. The
      presence of this post-translational modification is evident in crystal structures
      of these proteins. Harsh denaturation of proteins containing an acylimine bond
      results in partial polypeptide cleavage. For the red fluorescent protein DsRed,
      the extent of cleavage is quantitative. However, this is not the case for the
      blue non-fluorescent chromoprotein Rtms5, even though all chromophores in
      tetrameric Rtms5 contain an acylimine bond. We have identified two positions
      around the chromophore of Rtms5 where substitutions can promote or suppress the
      extent of cleavage on harsh denaturation. We propose a model in which cleavage of
      Rtms5 is facilitated by a trans to cis isomerisation of the chromophore.

PMID- 16414349
TI  - PI3 kinase is involved in cocaine behavioral sensitization and its reversal with
      brain area specificity.
AB  - Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved
      in cell differentiation, proliferation, survival, and phagocytosis, and may
      participate in various brain functions. To determine whether it is also involved
      in cocaine sensitization, we measured the p85alpha/p110 PI3K activity in the
      nuclear accumbens (NAc) shell, NAc core, and prefrontal cortex (PFC) following
      establishment of cocaine sensitization and its subsequent reversal. Naive rats
      were rank-ordered and split into either daily cocaine or saline pretreatment
      group based on their locomotor responses to an acute cocaine injection (7.5
      mg/kg, i.p.). These two groups were then injected with cocaine (40 mg/kg, s.c.)
      or saline for 4 consecutive days followed by 9-day withdrawal. Cocaine
      sensitization was subsequently reversed by 5 daily injections of the D1/D2
      agonist pergolide (0.1 mg/kg, s.c.) in combination with the 5-HT3 antagonist
      ondansetron (0.2 mg/kg, s.c., 3.5h after pergolide injection). After another 9
      day withdrawal, behavioral cocaine sensitization and its reversal were confirmed
      with an acute cocaine challenge (7.5 mg/kg, i.p.), and animals were sacrificed
      the next day for measurement of p85alpha/p110 PI3K activity. Cocaine-sensitized
      animals exhibited increased PI3K activity in the NAc shell, and this increase was
      reversed by combined pergolide/ondansetron treatment, which also reversed
      behavioral sensitization. In the NAc core and PFC, cocaine sensitization
      decreased and increased the PI3K activity, respectively. These changes, in
      contrast to that in the NAc shell, were not normalized following the reversal of
      cocaine-sensitization. Interestingly, daily injections of pergolide alone in
      saline-pretreated animals induced PI3K changes that were similar to the cocaine
      sensitization-associated changes in the NAc core and PFC but not the NAc shell;
      furthermore, these changes in saline-pretreated animals were prevented by
      ondansetron given 3.5h after pergolide. The present study suggests that selective
      enhancement of the PI3K activity in the NAc shell may be one of key alterations
      underlying the long-term cocaine sensitization. To the extent cocaine
      sensitization is an important factor in human cocaine abuse, pharmacological
      interventions targeted toward the NAc shell PI3K alteration may be useful in
      cocaine abuse treatment.

PMID- 16414350
TI  - KChIP2b modulates the affinity and use-dependent block of Kv4.3 by nifedipine.
AB  - Rapidly activating Kv4 voltage-gated ion channels are found in heart, brain, and
      diverse other tissues including colon and uterus. Kv4.3 can co-assemble with
      KChIP ancillary subunits, which modify kinetic behavior. We examined the affinity
      and use dependence of nifedipine block on Kv4.3 and its modulation by KChIP2b.
      Nifedipine (150 microM) reduced peak Kv4.3 current approximately 50%, but
      Kv4.3/KChIP2b current only approximately 27%. Nifedipine produced a very rapid
      component of open channel block in both Kv4.3 and Kv4.3/KChIP2b. However,
      recovery from the blocked/inactivated state was strongly sensitive to KChIP2b.
      Kv4.3 Thalf,recovery was slowed significantly by nifedipine (120.0+/-12.4 ms vs.
      213.1+/-18.2 ms), whereas KChIP2b eliminated nifedipine's effect on recovery:
      Kv4.3/KChIP2b Thalf,recovery was 45.3+/-7.2 ms (control) and 47.8+/-8.2 ms
      (nifedipine). Consequently, Kv4.3 exhibited use-dependent nifedipine block in
      response to a series of depolarizing pulses which was abolished by KChIP2b.
      KChIPs alter drug affinity and use dependence of Kv4.3.

PMID- 16414351
TI  - A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth
      through G0/G1 cell-cycle arrest.
AB  - Patients with pancreatic cancer have little hope for cure because no effective
      therapies are available. Sansalvamide A is a cyclic depsipeptide produced by a
      marine fungus. We investigated the effect of a novel sansalvamide A analogue on
      growth, cell-cycle phases, and induction of apoptosis in human pancreatic cancer
      cells in vitro. The sansalvamide analogue caused marked time- and concentration
      dependent inhibition of DNA synthesis and cell proliferation of two human
      pancreatic cancer cell lines (AsPC-1 and S2-013). The analogue induced G0/G1
      phase cell-cycle arrest and morphological changes suggesting induction of
      apoptosis. Apoptosis was confirmed by annexin V binding. This novel sansalvamide
      analogue inhibits growth of pancreatic cancer cells through G0/G1 arrest and
      induces apoptosis. Sansalvamide analogues may be valuable for the treatment of
      pancreatic cancer.

PMID- 16414352
TI  - Principal component analysis of DNA oligonucleotide structural data.
AB  - The microstructure of a DNA helix is characterized by several base pair and base
      step parameters such as twist, rise, roll, propeller twist, etc., in addition to
      conformational parameters such as the backbone and the glycosidic torsion angles.
      Among these only a few, which are independent of all others and of each other,
      may be used to precisely characterize the helix. The problem however is to
      identify these independent parameters. We have used principal component analysis
      to identify a relatively small set of independent parameters, with which to
      characterize each DNA helix. We show that these principal components clearly
      discriminate between A and B DNA helical types. The calculations further suggest
      that the microstructure of a DNA helix is better characterized using
      dinucleotides.

PMID- 16414353
TI  - Resistance of cathepsin L compared to elastase to proteolysis when complexed with
      the serpin endopin 2C, and recovery of cathepsin L activity.
AB  - This study demonstrates unique differences in the conformational nature of
      cathepsin L compared to elastase when complexed with the serpin endopin 2C,
      assessed by susceptibilities of protease/endopin 2C complexes to proteolysis by
      trypsin. Complexed and uncomplexed cathepsin L were resistant to degradation by
      trypsin, which indicated that trypsin cleavage sites within cathepsin L remain
      inaccessible when this cysteine protease is complexed with the endopin 2C serpin.
      In contrast, elastase in complexes with endopin 2C was degraded by trypsin, but
      uncomplexed elastase was not degraded. These results demonstrate a change in the
      conformational properties of trypsin cleavage sites within elastase when it is
      complexed with endopin 2C, compared to uncomplexed elastase. Cathepsin L
      complexes with endopin 2C were short-lived, but elastase complexes were stable.
      Furthermore, cathepsin L dissociated from complexes demonstrated recovery of
      cathepsin L activity, and reducing conditions provided optimum recovery of
      cathepsin L activity. These findings suggest that cathepsin L, when complexed
      with endopin 2C, maintains its general conformation in a manner that allows
      recovery of cathepsin L activity upon dissociation from endopin 2C. These results
      demonstrate differences in the relative conformational properties of the cysteine
      protease cathepsin L, compared to the serine protease elastase, in complexes with
      the serpin endopin 2C.

PMID- 16414354
TI  - Evidence for a role of Collapsin response mediator protein-2 in signaling
      pathways that regulate the proliferation of non-neuronal cells.
AB  - Collapsin response mediator protein-2 or Crmp-2 plays a critical role in the
      establishment of neuronal polarity. In this study, we present evidence that apart
      from its functions in neurodevelopment, Crmp-2 is also involved in pathways that
      regulate the proliferation of non-neuronal cells through its phosphorylation by
      regulatory proteins. We show that Crmp-2 undergoes dynamic phosphorylation
      changes in response to contact inhibition-induced quiescence and that
      hyperphosphorylation of Crmp-2 occurs in a tumor. We further suggest that de
      regulation of Crmp-2 phosphorylation levels at certain amino acid residues may
      lead to aberrant cell proliferation and consequently, tumorigenesis.

PMID- 16414355
TI  - Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the
      intestine.
AB  - Niemann-Pick C1 like 1 (NPC1L1) is a protein critical for intestinal cholesterol
      absorption. The nuclear receptors peroxisome proliferator-activated receptor
      alpha (PPARalpha) and liver X receptors (LXRalpha and LXRbeta) are major
      regulators of cholesterol homeostasis and their activation results in a reduced
      absorption of intestinal cholesterol. The goal of this study was to define the
      role of PPARalpha and LXR nuclear receptors in the regulation of NPC1L1 gene
      expression. We show that LXR activators down-regulate NPC1L1 mRNA levels in the
      human enterocyte cell line Caco-2/TC7, whereas PPARalpha ligands have no effect.
      Furthermore, NPC1L1 mRNA levels are decreased in vivo, in duodenum of mice
      treated with the LXR agonist T0901317. In conclusion, the present study
      identifies NPC1L1 as a novel LXR target gene further supporting a crucial role of
      LXR in intestinal cholesterol homeostasis.

PMID- 16414356
TI  - Regulation by sphingosine 1-phosphate of Bax and Bad activities during apoptosis
      in a MEK-dependent manner.
AB  - Herein we report that the prosurvival sphingolipid sphingosine 1-phosphate
      regulates the activities of both Bad and Bax during apoptosis of Jurkat cells.
      First, sphingosine 1-phosphate treatment results in Bad inactivation via the
      ERK/Rsk-1 pathway. Second, sphingosine 1-phosphate blocks the translocation of
      Bax to the mitochondria induced by Fas ligation. MEK inhibition by PD98059 or
      U0126 not only abrogates sphingosine 1-phosphate-induced Bad phosphorylation, but
      also its cytoprotective effect. Furthermore, inhibition of both mitochondrial
      cytochrome c efflux and Bax translocation to the mitochondria by sphingosine 1
      phosphate could be overcome by PD98059 or U0126. Hence, the MEK/ERK pathway seems
      to be crucial for the survival effects initiated by sphingosine 1-phosphate.

PMID- 16414357
TI  - cAMP elevating agents suppress secretory phospholipase A(2)-induced matrix
      metalloproteinase-2 activation.
AB  - Phospholipase A2 proteins are major regulators of the arachidonic acid cascade
      and are involved in various cellular responses. Previously, we reported that
      group IB PLA2 proteins stimulate MMP-2 activation and subsequent cell migration.
      Here, we describe a novel mechanism whereby sPLA2-induced proMMP-2 activation is
      regulated by intracellular cAMP in HT1080 cells, although sPLA2 itself had no
      effect on the regulation of cAMP levels. Exogenous dibutyryl cAMP (a cAMP
      analogue) strongly inhibited proMMP-2 activation, and cAMP elevating agents,
      namely, cholera toxin (a Gs activator) and forskolin (an adenylyl cyclase
      activator), abrogated basal and sPLA2-induced proMMP-2 activation. We also found
      that the down-regulation of TIMP-2 expression and extracellular signal-regulated
      kinase (ERK)1/2 activation by sPLA2 were blocked by increasing the intracellular
      cAMP level. Taken together, our data indicate that sPLA2-induced proMMP-2
      activation is influenced by intracellular cAMP levels via the modulations of TIMP
      2 expression and ERK1/2 activation.

PMID- 16414358
TI  - Mucopolysaccharidoses and the eye.
AB  - The mucopolysaccharidoses (MPSs) are a group of disorders caused by inherited
      defects in lysosomal enzymes resulting in widespread intra- and extra-cellular
      accumulation of glycosaminoglycans. They have been subdivided according to enzyme
      defect and systemic manifestations and include MPS IH (Hurler), MPS IS (Scheie),
      MPS IH/S (Hurler/Sheie), MPS II (Hunter), MPS III (Sanfilippo), MPS IV (Morquio),
      MPS VI (Maroteaux-Lamy), MPS VII (Sly) and MPS IX (Natowicz). The
      mucopolysaccharidoses have a spectrum of systemic manifestations, including
      airway and respiratory compromise, skeletal deformities, intellectual and
      neurological impairment, cardiac abnormalities, and gastrointestinal problems.
      Ocular manifestations are common in the mucopolysaccharidoses and may result in
      significant visual impairment. Corneal opacification of varying severity is
      frequently seen, as well as retinopathy, optic nerve swelling and atrophy, ocular
      hypertension, and glaucoma. New treatment modalities for the systemic
      manifestations of the mucopolysaccharidoses include bone marrow transplant and
      enzyme replacement therapy, and have resulted in an improved prognosis in many
      cases. This article reviews the systemic and ocular manifestations of the
      mucopolysaccharidoses, as well as new treatment options, and discusses the
      ophthalmic management of mucopolysaccharidosis patients.

PMID- 16414359
TI  - Update on ocular complications of systemic cancer chemotherapy.
AB  - The constantly growing list of cytotoxic chemotherapeutics requires a new survey
      of ophthalmic complications, which are often underestimated. Based on the review
      by Imperia et al (1989), an update on ophthalmic complications of currently used
      cytotoxic chemotherapeutics in oncology was written. Vision is a quality of life
      issue, which must be nurtured, especially if loss of vision can be prevented. The
      broad spectrum of ophthalmic complications induced by cytotoxic chemotherapy
      includes reversible and irreversible acute and chronic disorders. Mild to
      moderate ophthalmic complications are very common and reversible after cessation
      of anti-cancer therapy. Some major ocular toxicities may require a dose reduction
      or the discontinuation of cytotoxic chemotherapy in order to prevent visual loss.
      Ocular toxicities can be treated or even prevented, if detected early enough.
      That is why an ophthalmic baseline examination for patients receiving cytosine
      arabinoside, 5-fluorourocil, methotrexate, or docetaxel should be taken into
      consideration, and a consultation with an ophthalmologist has to be done as soon
      as symptoms are recognized. Oncologists and ophthalmologists must be aware of
      potential ophthalmic complications during cytotoxic chemotherapy, and should work
      together.

PMID- 16414361
TI  - Lens regeneration in mammals: a review.
AB  - Lens regeneration occurs in New Zealand albino rabbits after endocapsular lens
      extraction, if the anterior and posterior capsules remain relatively intact.
      Research beginning in the 19th century showed that regeneration of the lens
      begins as early as 2 weeks postoperatively, depends on the size of the
      capsulotomy and how it has scarred, and is faster in younger animals. More
      recently, implantation of embryonic ectoderm at the time of lens removal has been
      shown to improve the growth and quality of the regenerated lenses. Lens fiber
      differentiation follows a process similar to embryological development with
      proliferation of epithelial cells along the anterior and posterior capsule,
      elongation of the posterior epithelial cells, and differentiation into lens
      fibers. Signals required for lens fiber differentiation include FGF, IGF-1, and
      TGF-beta. Identifying other signals, and providing these factors to the
      regenerating lens, could speed up lens regeneration and improve normality of the
      resulting structure. The regenerated lenses contain the same proteins as normal
      lenses, including all the major crystallins (alpha, beta, and gamma). However,
      regenerated lenses have typically been irregular in shape due to lack of lens
      growth at the site of the anterior capsulotomy and its adhesion to the posterior
      capsule. Sealing the capsulotomy and refilling the bag to maintain its shape seem
      to allow for more normal lens regeneration. Lens regeneration is a potential
      approach to restoring normal vision after cataract surgery. Importantly, lenses
      have been shown to regenerate after removal of cataracts in several mammals, and
      primate lenses do have regenerative capability.

PMID- 16414362
TI  - Jumping Jack Flash.
AB  - A 38-year-old woman presented with blurred vision and "jumping" of the right eye
      for 7 months. Magnetic resonance imaging of the head was normal. Intermittent
      intorsion of the right eye was noted on examination, consistent with superior
      oblique myokymia. She was initially treated with carbamazepine but stopped after
      becoming light-headed. The diagnosis and treatment of superior oblique myokymia
      are discussed.

PMID- 16414360
TI  - Primary testicular and intraocular lymphomas: two case reports and a review of
      the literature.
AB  - Testicular lymphoma is a rare neoplasm of the testis that is most commonly seen
      in older patients. It metastasizes preferentially to extranodal sites, including
      the skin, central nervous system, Waldeyer ring, contralateral testis, and lung.
      Two case reports of patients with a history of testicular lymphoma who developed
      involvement of the vitreous and retina are presented. These are interesting cases
      as the testis, central nervous system, and eye are all immune privileged organs,
      which may account for occurrence of disease in these sites. Histopathologic
      examination of diagnostic vitrectomy specimens from both cases showed atypical
      lymphoid cells with immunoglobulin heavy chain (IgH) gene rearrangements,
      consistent with the diagnosis of intraocular B-cell lymphoma. The results of a
      literature review of all reports of ocular involvement with testicular lymphoma
      are discussed. Patients with testicular lymphoma are at risk for relapse,
      particularly in the central nervous system. Clinicians should be suspicious for
      intraocular lymphoma in patients with a history of testicular lymphoma who
      present with vitritis or retinal lesions.

PMID- 16414363
TI  - A diplopia dilemma.
AB  - A 38-year-old man experienced double vision with pupillary abnormalities and
      convergence retraction nystagmus. A mass, which responded to radiation therapy,
      was seen as the cause of his dorsal midbrain syndrome. The neural control of
      vertical eye movements is reviewed and the management of a third ventricular
      pineal region mass discussed.

PMID- 16414364
TI  - Depth-of-focus of the human eye: theory and clinical implications.
AB  - The depth-of-focus, or the perceptual tolerance of the human eye to retinal
      defocus, is important to and imbedded in many aspects of clinical refraction and
      physiological optics. Although the depth-of-focus is a common concept in
      classical optics, there is relatively little detailed discussion of its
      implications as related to normal vision function and to vision anomalies. With
      current advances in refractive surgery and ophthalmic lens design, the demand for
      knowledge in this topic is both timely and important. This review of our current
      understanding of the depth-of-focus should prove to be useful to clinicians,
      researchers, and students as an introduction to the subject. Two areas will be
      considered: 1) basic definitions of and factors affecting the depth-of-focus, and
      2) its contemporary clinical implications.

PMID- 16414366
TI  - MRA or CTA, that's the question.

PMID- 16414369
TI  - Conformity index: a review.
AB  - We present a critical analysis of the conformity indices described in the
      literature and an evaluation of their field of application. Three-dimensional
      conformal radiotherapy, with or without intensity modulation, is based on medical
      imaging techniques, three-dimensional dosimetry software, compression
      accessories, and verification procedures. It consists of delineating target
      volumes and critical healthy tissues to select the best combination of beams.
      This approach allows better adaptation of the isodose to the tumor volume, while
      limiting irradiation of healthy tissues. Tools must be developed to evaluate the
      quality of proposed treatment plans. Dosimetry software provides the dose
      distribution in each CT section and dose-volume histograms without really
      indicating the degree of conformity. The conformity index is a complementary tool
      that attributes a score to a treatment plan or that can compare several treatment
      plans for the same patient. The future of conformal index in everyday practice
      therefore remains unclear.

PMID- 16414370
TI  - Radiation sensitization with redox modulators: a promising approach.
AB  - PURPOSE: Radiation therapy plays a critical role in the local and regional
      control of malignant tumors. Its efficacy, however, is limited by a number of
      factors, including toxicity, tumor hypoxia, and tumor genetics. Recent attempts
      to enhance the efficacy of radiation therapy have focused on biologic agents that
      modulate reduction/oxidation reactions within tumor cells. METHODS AND MATERIALS:
      We review five promising redox modulators that are in development. Tirapazamine
      and AQ4N are known as "hypoxic cell sensitizers" and are toxic in areas of low
      oxygen tension. RSR13 facilitates delivery of oxygen to tumor cells, thereby
      rendering them more sensitive to radiation. Motexafin gadolinium, with a
      porphyrin-like structure, selectively accumulates in tumor cells and thereby
      enhances radiation-induced DNA damage. HIF-1 inhibitors target a transcription
      factor that regulates hypoxia-related events and cell survival. RESULTS: Our
      review of each agent included a thorough search of published preclinical and
      clinical data, including that presented in abstracts and posters at international
      meetings. Our objectives were not to identify a superior mechanism or drug, but
      rather to summarize the available safety and efficacy data. CONCLUSION: Clearly,
      there is an unmet need for safer agents that augment the efficacy of radiation
      therapy. This review highlights five promising redox modulators that are in
      development. None has yet been approved by the Food and Drug Administration.
      These drugs were selected for discussion because they exemplify the current
      investigative landscape of radiosensitizers and are indicative of future
      directions in this area. These radiation sensitizers have the potential to
      succeed where others have failed, by locally increasing the radiosensitivity of
      tumor cells without enhancing that of surrounding normal tissues.

PMID- 16414371
TI  - Tumor radiosensitizers--current status of development of various approaches:
      report of an International Atomic Energy Agency meeting.
AB  - PURPOSE: The International Atomic Energy Agency (IAEA) held a Technical Meeting
      of Consultants to (1) discuss a selection of relatively new agents, not those
      well-established in clinical practice, that operated through a variety of
      mechanisms to sensitize tumors to radiation and (2) to compare and contrast their
      tumor efficacy, normal tissue toxicity, and status of development regarding
      clinical application. The aim was to advise the IAEA as to which developing agent
      or class of agents would be worth promoting further, by supporting additional
      laboratory research or clinical trials, with the eventual goal of improving
      cancer control rates using radiotherapy, in developing countries in particular.
      RESULTS: The agents under discussion included a wide, but not complete, range of
      different types of drugs, and antibodies that interfered with molecules in cell
      signaling pathways. These were contrasted with new molecular antisense and gene
      therapy strategies. All the drugs discussed have previously been shown to act as
      tumor cell radiosensitizers or to kill hypoxic cells present in tumors.
      CONCLUSION: Specific recommendations were made for more preclinical studies with
      certain of the agents and for clinical trials that would be suitable for
      industrialized countries, as well as trials that were considered more appropriate
      for developing countries.

PMID- 16414372
TI  - Radiation induced DNA damage and damage repair in human tumor and fibroblast cell
      lines assessed by histone H2AX phosphorylation.
AB  - PURPOSE: To analyze the radiation-induced levels of gammaH2AX and its decay
      kinetics in 10 human cell lines covering a wide range of cellular
      radiosensitivity (SF2, 0.06-0.63). METHODS AND MATERIALS: Five tumor cell lines
      included Colo-800 melanoma, two glioblastoma (MO59J and MO59K), fibrosarcoma HT
      1080, and breast carcinoma MCF7. Five primary skin fibroblasts lines included two
      normal strains, an ataxia telangiectasia strain, and two fibroblast strains from
      breast cancer patients with an adverse early skin reaction to radiotherapy.
      Cellular radiosensitivity was assessed by colony-forming test. Deoxyribonucleic
      acid damage and repair were analyzed according to nuclear gammaH2AX foci
      intensity, with digital image analysis. RESULTS: The cell lines tested showed a
      wide degree of variation in the background intensity of immunostained nuclear
      histone gammaH2AX, which was higher for the tumor cell lines compared with the
      fibroblast strains. It was not possible to predict clonogenic cell survival (SF2)
      for the 10 cell lines studied from the radiation-induced gammaH2AX intensity. In
      addition, the slopes of the dose-response (0-4 Gy) curves, the rates of gammaH2AX
      disappearance, and its residual expression (<or=18 h after irradiation) did not
      correlate with SF2 values. CONCLUSIONS: The results from 10 cell lines showed
      that measurements of immunofluorescence intensity by digital image analysis of
      phosphorylated histone H2AX as a surrogate marker of DNA double-strand breaks did
      not allow reliable ranking of cell strains according to their clonogenic survival
      after irradiation.

PMID- 16414373
TI  - Inhibition of lung tumor growth and augmentation of radiosensitivity by
      decreasing peroxiredoxin I expression.
AB  - PURPOSE: In this study, we examined the role of peroxiredoxin I (Prx I) in lung
      cancer cell growth in vitro and in vivo and its influence on these tumor cells'
      sensitivity to radiotherapy. METHODS AND MATERIALS: We established stable
      transfectants of A549 (p53+) and H1299 (p53-) lung carcinoma cell lines with Prx
      I antisense to downregulate their Prx I protein. We then examined their in vitro
      biologic changes and used nude mice xenografts of these cell lines to compare
      tumor invasion, spontaneous metastatic capacity, and sensitivity to radiotherapy.
      RESULTS: The Prx I antisense transfectants of both cell lines showed a
      significant reduction in Prx I protein production. Prx I antisense transfectants
      grew more slowly than did the wild type. As xenografts in mice, A549 Prx I
      antisense transfectants showed a threefold delay in the generation of palpable
      tumors. The incidence of spontaneous metastasis of Prx I antisense transfectants
      was significantly less than that of the wild-type cells. Furthermore, irradiation
      of Prx I antisense transfectants caused more than twice the growth delay compared
      with the wild type. CONCLUSION: The results of these studies suggest that
      inactivation of Prx I may be a promising approach to improve the treatment
      outcome of patients with lung cancer.

PMID- 16414374
TI  - The mobilization of hematopoietic progenitors to peripheral blood is predictive
      of the hematopoietic syndrome after total or partial body irradiation of mice.
AB  - PURPOSE: In previous studies we showed that administration of mobilizing growth
      factors (MGFs) to mice previously exposed to total body irradiation mobilizes to
      peripheral blood (PB) a number of progenitors that correlates with the total
      reserve of progenitors surviving the exposure. Now we have tested whether this
      finding is independent of the radiosensitivity of the mice and of the homogeneity
      of the radiation exposure. Also we have investigated whether numbers of mobilized
      progenitors predict the hematopoietic syndrome after irradiation. METHODS AND
      MATERIALS: Mice were subjected to partial or total body irradiation and treated
      with MGFs. Thereafter, the number of colony-forming units granulocyte-macrophage
      progenitors in PB was correlated with the total reserve of surviving progenitors
      and with the nadir of leukocytes after the irradiation. RESULTS: The number of
      progenitors mobilized to PB after irradiation of normal and radiosensitive mice
      showed the same correlation with respect to the reserve of bone marrow
      progenitors surviving the exposure. Additionally, the number of mobilized
      progenitors correlated with the leukocytes' nadir after the irradiation,
      regardless of homogeneous or inhomogeneous exposures. CONCLUSIONS: In a mouse
      experimental model, the number of hematopoietic progenitors mobilized to PB by
      MGFs is a good predictor of the hematopoietic syndrome occurring after total or
      partial body irradiation.

PMID- 16414375
TI  - Radiobiologic effect of intermittent radiation exposure in murine tumors.
AB  - PURPOSE: In stereotactic irradiation using a linear accelerator, the effect of
      radiation may be reduced during intermittent exposures owing to recovery from
      sublethal damage in tumor cells. After our previous in vitro study suggesting
      this phenomenon, we investigated the issue in murine tumors. METHODS AND
      MATERIALS: We used EMT6 and SCCVII tumors approximately 1 cm in diameter growing
      in the hind legs of syngeneic mice. Three schedules of intermittent radiation
      were investigated. First, 2 fractions of 10 Gy were given at an interval of 15
      360 min to investigate the pattern of recovery from sublethal damage. Second, 5
      fractions of 4 Gy were given with interfraction intervals of 2.5-15 min each.
      Third, 10 fractions of 2 Gy were given with interfraction intervals of 1-7 min
      each. Doses of 15-20 Gy were also given without interruption to estimate the dose
      modifying factors. Tumors were excised 20 h later, and tumor cell survival was
      determined by an in vivo-in vitro assay. RESULTS: In the 2-fraction experiment,
      the increase in cell survival with elongation of the interval was much less than
      that observed in our previous in vitro study. In the 5- and 10-fraction
      experiments, no significant increase in cell survival was observed after the
      intermittent exposures. Moreover, cell survival decreased at most points of the 5
      fraction experiments by interruption of radiation in both EMT6 and SCCVII tumors.
      In the 10-fraction experiment, cell survival also decreased when the interruption
      was 3 or 7 min in EMT6 tumors. CONCLUSION: The results of the present in vivo
      studies were different from those of our in vitro studies in which cell survival
      increased significantly when a few minutes or longer intervals were posed between
      fractions. This suggests that recovery from sublethal damage in vivo may be
      counterbalanced by other phenomena such as reoxygenation that sensitizes tumor
      cells to subsequent irradiation.

PMID- 16414376
TI  - Examination of GyE system for HIMAC carbon therapy.
AB  - PURPOSE: A retrospective analysis was made to examine appropriateness in the
      estimation of the biologic effectiveness of carbon-ion radiotherapy using
      resultant data from clinical trials at the heavy-ion medical accelerator complex
      (HIMAC) at the National Institute of Radiological Sciences in Chiba, Japan.
      METHODS AND MATERIALS: At HIMAC, relative biologic effectiveness (RBE) values of
      therapeutic carbon beams were determined based on experimental results of cell
      responses, on values expected with the linear-quadratic model, and based on
      experiences with neutron therapy. We use fixed RBE values independent of dose
      levels, although this apparently contradicts radiobiologic observations. Our RBE
      system depends only on LET of the heavy-ion radiation fields. With this RBE
      system, over 2,000 patients have been treated by carbon beams. With data from
      these patients, the local control rate of non-small-cell lung cancer was analyzed
      to verify the clinical RBE of the carbon beam. The local control rate was
      compared with rates published by groups from Gunma University and Massachusetts
      General Hospital. Using a simplified tumor control probability (TCP) model,
      clinical RBE values were obtained for different levels of TCP. RESULTS: For the
      50% level of the clinical TCP, the RBE values nearly coincide with those for in
      vitro human salivary gland cell survival at 10%. For the higher levels of
      clinical TCP, the RBE values approach closer to those adapted in clinical trials
      at HIMAC.

PMID- 16414377
TI  - In response to Dr. Formenti et al. (Int J Radiat Oncol Biol Phys 2005, 63:1275
      1276).

PMID- 16414368
TI  - Comparative analysis of the expressed genome of the infective juvenile
      entomopathogenic nematode, Heterorhabditis bacteriophora.
AB  - We report the first cDNA-sequencing project of the entomopathogenic nematode,
      Heterorhabditis bacteriophora. A total of 1246 expressed sequence tags (ESTs)
      were generated by random sequencing of clones from a cDNA library of the
      infective juvenile stage. The ESTs were annotated resulting in 1072 useful ESTs
      that were categorized into functional categories according to Kyoto Encyclopedia
      of Genes and Genomes. Approximately 459 of 1072 ESTs (43%) had significant
      similarities to annotated sequences in GenBank. Of these, 417 had significant
      similarities to the free-living nematode Caenorhanditis elegans proteins. Most
      ESTs (18%) belonged to the genetic information processing category followed by
      metabolism (15% ESTs) and environmental information processing (15%) pathways.
      Several interesting ESTs were found that may have roles in the infectivity and
      survival of infective juveniles. These included proteases, dauer pathway genes
      (akt-1, pdk-1 & daf-7) and aging and stress resistance genes such as superoxide
      dismutase (sod-4), heat shock genes (hsp-4 & hsp-6), and eat genes, and signaling
      proteins like G-protein coupled receptors, regulators of G-protein signaling
      (rgs), and serine/threonine kinases. Other interesting ESTs include systemic RNAi
      defective protein (sid-1), ribonuclease III family members (rnh-2 &rnc) and
      transposase gene (Tc3A). About 67% of the ESTs did not find matches in any of the
      searched databases suggesting potentially novel genes in this enomopathogenic
      nematode. Note: Sequences described in this paper have been deposited in Genbank
      under the accessions DN 152655-DN 152999, and DN 153000-DN 153726.

PMID- 16414379
TI  - Abdominal aortic aneurysm sac shrinkage after endovascular aneurysm repair:
      correlation with chronic sac pressure measurement.
AB  - OBJECTIVES: Abdominal aortic aneurysm (AAA) sac shrinkage after endovascular
      aneurysm repair (EVAR) is considered to be evidence of clinical success.
      Exclusion of the sac from systemic pressure is the likely cause of shrinkage. We
      report our continuing clinical experience with the use of a permanently
      implantable, ultrasound-activated remote pressure transducer to measure intrasac
      pressure and its correlation with changes in sac diameter over time. METHODS:
      Over a 22-month period, 21 patients underwent EVAR of an infrarenal AAA with
      implantation of an ultrasound-activated remote pressure transducer fixed to the
      outside of the stent-graft and exposed to the excluded aortic sac. Intrasac
      pressures were measured directly with an intravascular catheter and by the remote
      sensor at the time of stent-graft deployment. Follow-up sac pressures were
      measured by remote sensor and compared with systemic arterial pressure at every
      follow-up visit. Mean follow-up was 11.4 +/- 5.0 months (range, 1 to 26 months).
      Twenty patients had follow-up of > or =6 months. Mean pressure index (MPI) was
      calculated as the ratio of mean sac pressure to mean systemic pressure. RESULTS:
      Pressures could be obtained at all visits in 15 of the 21 patients. Fourteen of
      these 15 patients had follow-up of at least 6 months. Aneurysm sac shrinkage of
      >5 mm was seen in seven (50%) of these 14 patients. No aneurysm enlargement was
      observed in any patient. The MPI was significantly lower in patients with sac
      shrinkage at 6 months and at final follow-up. CONCLUSIONS: Endovascular aneurysm
      repair results in marked reduction of sac pressure in most patients. Patients
      with aneurysm shrinkage after EVAR have significantly lower MPI; however, the
      absence of sac shrinkage does not imply persistent pressurization of the sac.
      Further clinical follow-up will delineate the role of long-term sac pressure
      monitoring in surveillance after EVAR.

PMID- 16414380
TI  - Outcomes of accessory renal artery occlusion during endovascular aneurysm repair.
AB  - OBJECTIVE: Accessory renal arteries are frequently encountered when patients are
      evaluated for endovascular abdominal aortic aneurysm repair (EVAR). Some have
      considered their presence a contraindication to EVAR in fear of endoleak and the
      end result of renal function. We sought to determine whether the coverage of
      accessory renal arteries during EVAR was associated with any adverse sequelae.
      METHODS: Retrospective review of the medical records and computed tomographic
      scans of all patients undergoing EVAR (1998 to 2003) was performed. Note was made
      of the presence or absence of accessory renal arteries, hypertension, and renal
      function. Preoperative computed tomographic images were compared with
      postoperative images to determine the presence of renal infarction. A control
      group of 26 consecutive patients without accessory renal arteries was used for
      comparison of the results of EVAR. RESULTS: EVAR was performed in 550 patients
      over the study interval. The mean follow-up was 16 months (range, 1-48 months).
      The average age was 74 years (range, 57-90 years). Thirty-five patients (6.6%; 32
      male and 3 female) were documented to have accessory renal arteries; the average
      number of accessory arteries was 2 (range, 1-4). Bilateral accessory arteries
      were present in 13 patients: all but 1 patient (n = 34) had a left-sided
      accessory renal artery, and 23 had a right-sided accessory renal artery. EVAR was
      performed with a variety of endografts: AneuRx (n = 10), Talent (n = 7),
      PowerLink (n = 7), Zenith (n = 5), LifePath (n = 4), and Ancure (n = 2). There
      were no mortalities. Twelve endoleaks were documented: three type I, eight type
      II, and one type III. The accessory renal arteries were not implicated in any of
      the endoleaks, and none of these accessory vessels was embolized before or after
      EVAR. Seven patients (20%) had renal infarcts associated with EVAR that were
      noted on follow-up computed tomographic scans. The mean follow-up for patients
      with segmental infarction was 23 months (range, 8-48 months). Hypertensive status
      did not change in any patient in whom an accessory renal artery had been covered.
      The average serum creatinine was 1.08 mg/dL (range, 0.6-1.8 mg/dL) before EVAR in
      patients with accessory renal arteries covered by an endovascular graft and did
      not change significantly in response to EVAR. Serum creatinine increased almost
      twofold in two patients but spontaneously resolved in follow-up. The average
      preoperative creatinine clearance was 79 mL/min (range, 35-166 mL/min) in
      patients without an accessory renal artery and was 80 mL/min (range, 35-167
      mL/min) after EVAR. The average preoperative creatinine clearance was 67 mL/min
      (range, 31-137 mL/min) in patients with an accessory renal artery and 68 mL/min
      (range, 45-83 mL/min) in patients with renal infarcts. None of the patients
      required temporary or permanent dialysis. There was no difference between control
      patients and patients with covered accessory renal arteries with respect to
      hypertensive status, presence of renal infarcts, serum creatinine, or creatinine
      clearance after EVAR. CONCLUSIONS: Occlusion of accessory renal arteries is not
      associated with clinically significant signs or symptoms, even in patients with
      mild or moderate renal insufficiency. Sacrifice of accessory renal arteries most
      commonly does not lead to detectable renal infarction, either clinically or
      radiographically. When segmental infarction of the kidney does result, it seems
      to be well tolerated in this group of patients. Accessory renal arteries were not
      found to contribute to endoleaks and should not be prophylactically embolized.

PMID- 16414381
TI  - Glomerular filtration rate is a predictor of mortality after endovascular
      abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Clinically evident renal disease is a risk factor for mortality after
      aneurysm repair. Serum creatinine is widely used as a measure of renal function
      in the preoperative evaluation of patients. Unfortunately, serum creatinine
      concentration is influenced by muscle mass, hydration status, and glomerular
      filtration rate (GFR). Calculated GFR, which takes predictors of muscle mass such
      as age, gender, and weight into account, is a more sensitive determinant of renal
      function than serum creatinine. We hypothesized that GFR would more accurately
      predict mortality after EVAR than serum creatinine. METHODS: We retrospectively
      evaluated our database of 398 patients who underwent EVAR with the AneuRx device
      between October 1999 and October 2004. There were 340 men and 58 women with a
      mean age of 73. GFR was calculated using the Cockcroft-Gault equation. The
      patients were divided into four quartiles by preoperative GFR: I (7 to 45), II
      (45 to 60), III (61 to 79), and IV (> or =80). Survival was estimated with the
      Kaplan-Meier method, and heterogeneity of mortality across strata was evaluated
      using the log-rank test. The GFR quartiles were compared with clinically accepted
      criteria for abnormal renal function (serum creatinine level > or =1.7). RESULTS:
      Actuarial survival at 48 months was 61.5%, 70.5%, 86.0%, and 85.7% for GFR
      quartiles I to IV, respectively (P < .003). Thirty-day mortality was 2.2% in
      quartile I, 3.2% in quartile II, and 0 in quartiles III and IV (P = .03 for q1 +
      q2 vs q3 + q4, P < .02 for q2 vs q3 + q4). Survival curves for quartiles II to IV
      were statistically indistinguishable, with quartile II running tangential to the
      two higher quartiles after the perioperative period. Quartile I fared
      significantly worse than the other three quartiles for the entire follow-up
      period (P < .005). According to American Kidney Foundation criteria (GFR <90),
      83.3% of patients had abnormal renal function compared with 16.1% with abnormal
      serum creatinine (>1.7) (P < .0002). CONCLUSION: The risk of perioperative and
      long-term mortality in patients undergoing EVAR is more accurately stratified by
      using calculated GFR than serum creatinine alone. A GFR <45 is associated with
      decreased survival after EVAR. Perioperative mortality at a GFR of 45 to 60 is
      comparable with that of the lower quartile (GFR <45), but late survival is
      comparable with that of patients with GFR >60. The finding of increased risk of
      early mortality in patients in the 45 to 60 GFR range, with survivors enjoying
      good long-term outcome, suggests that these patients may most benefit from the
      use of alternative contrast agents and periprocedural renal protection
      techniques.

PMID- 16414382
TI  - Endovascular aneurysm repair with suprarenal vs infrarenal fixation: a study of
      renal effects.
AB  - OBJECTIVES: Although suprarenal fixation may be of benefit during endovascular
      aneurysm repair (EVAR), its safety with regards to renal effects remains
      uncertain. To date, there has been no controlled study of the topic, with most
      reports relying upon single-center experiences that use heterogeneous patient
      populations and devices from different manufacturers. The purpose of this
      analysis was to evaluate the effect of suprarenal fixation on renal function by
      comparing homogeneous patient populations receiving EVAR grafts from a single
      manufacturer that are identical in design and delivery method, except for
      utilizing either suprarenal (SR) or infrarenal (IR) fixation. METHODS: During two
      pivotal US Food and Drug Administration trials, 283 patients underwent EVAR with
      the Powerlink bifurcated graft. The trials' inclusion and exclusion criteria and
      grafts were identical except for fixation scheme. Clinical, laboratory, and
      computed tomographic (CT) data were retrospectively reviewed. A comparison of
      preoperative, perioperative (1 to 7 days), and postoperative (>7 days)
      alterations in serum creatinine (SCr), creatinine clearance (CrCl), and blood
      pressure was performed. Renal adverse events were determined by CT scan and
      clinical chart review and included renal infarction, renal artery stenosis
      (either progressive or requiring renal stent placement), and renal artery
      occlusion. RESULTS: Both SR and IR groups demonstrated a significant increase in
      SCr and a decrease in CrCl over time. No significant difference in SCr or CrCl
      existed between groups during any time period. There were no differences in
      postoperative renal impairment (IR, 10.2%; SR, 7.6%, P = .634), the need for
      hemodialysis (IR, 0.7%; SR, 0%, P = 1.00), or systolic and diastolic blood
      pressure during subsequent follow-up between treatment groups. There was no
      significant difference in the number of renal adverse events detected by CT
      between the IR (10, 6.8%) and SR (3, 3.8%) groups (P = .550). CONCLUSION:
      Suprarenal fixation does not lead to a significant increase in acute renal
      events, renal impairment, or alteration in blood pressure compared with
      infrarenal fixation. Patients undergoing aneurysm repair with devices that use
      either suprarenal or infrarenal fixation develop progressive renal dysfunction
      over time. Further studies are needed to determine the long-term effects of
      suprarenal fixation on renal function and progression of renal artery stenosis.

PMID- 16414383
TI  - Aortic neck morphology after endovascular repair of descending thoracic aortic
      aneurysms.
AB  - BACKGROUND: Endovascular repair has emerged as a less-invasive treatment for
      descending thoracic aortic (DTA) aneurysms. However, the durability of this
      procedure relies on the stability of proximal and distal fixation sites. This
      study analyzes 3 years of computed tomography (CT) data on aortic neck morphology
      after endovascular DTA aneurysm repair. METHODS: Between 1999 and 2001, 139
      patients underwent successful endovascular DTA repair as part of a prospective,
      multicenter clinical trial investigating the Gore TAG thoracic endoprosthesis.
      Contrast-enhanced, high-resolution CT scans were obtained at 1 (baseline), 12,
      24, and 36 months and submitted to an independent core laboratory for image
      analysis. The aorta was carefully measured by using computerized planimetry and a
      standardized protocol. Neck diameter was measured at 10-mm intervals for 2 cm
      above and below the aneurysm and correlated with graft migration and endoleak.
      RESULTS: The mean proximal neck diameter increased from a baseline of 30.2 +/-
      4.6 mm to 32.0 +/- 4.3 mm at 36 months (P <.05), and the annual diameter increase
      was 0.8, 0.4, and 0.6 mm at 12, 24, and 36 months. The mean distal neck diameter
      increased from 29.4 +/- 3.8 mm to 32.1 +/- 5.0 mm at 36 months (P <.05), and the
      annual diameter increase was 1.1, 0.4, and 1.2 mm at 12, 24, and 36 months. At 36
      months, freedom from neck dilation of > or =5 mm was 87%, and freedom from
      migration of > or =10 mm was 83%. An endoleak was present in 11 (9%) of 122
      patients at baseline, 7 (7%) of 96 at 12 months, 6 (9%) of 68 at 24 months, and 1
      (3%) of 33 at 36 months. Neck dilation was not associated with graft migration or
      endoleak. CONCLUSIONS: Three years after endovascular repair of DTA aneurysms,
      there is progressive enlargement of the proximal and distal aortic necks.
      Although uncommon for patients to develop significant neck dilation, when it does
      occur, it is not associated with graft migration or endoleak. Continued
      surveillance of aortic neck morphology after descending thoracic aneurysm
      endografting is recommended.

PMID- 16414384
TI  - Endovascular management of iliac artery occlusions: extending treatment to
      TransAtlantic Inter-Society Consensus class C and D patients.
AB  - OBJECTIVE: The preferential use of endovascular techniques to treat complex
      aortoiliac disease has increased in recent years. The purpose of this study was
      to review the outcomes and durability of recanalization, percutaneous
      transluminal angioplasty, and stenting for iliac occlusions based on the
      patient's TransAtlantic Inter-Society Consensus (TASC) stratification. METHODS:
      Between 1998 and 2004, more than 628 patients with a clinical diagnosis of
      aortoiliac atherosclerotic disease underwent arteriography. The endovascular
      treatment of 89 consecutive patients (mean age, 66 years; 58% male) with
      symptomatic iliac occlusions (TASC-B, -C, and -D) was the basis for this study.
      Original angiographic imaging was evaluated for lesion grade and runoff.
      Electronic and hard copy medical records were reviewed for demographic data,
      clinical variables, and noninvasive vascular laboratory testing. Kaplan-Meier
      estimators were used to determine patency rates according to Society for Vascular
      Surgery criteria. Univariate and multivariate analyses were performed. P values
      of <.05 were considered significant. RESULTS: Recanalization and percutaneous
      transluminal angioplasty/stenting (total, 178 stents) of occluded iliac arteries
      was technically successful in 84 (91%) of 92 procedures. Patients in the TASC-C
      and -D groups often required multiple access sites (50%) and femoral artery
      endarterectomy/patch angioplasty for diffuse disease (24%). The mean ankle
      brachial index increased from 0.45 to 0.83. Distal embolization led to major
      amputation and eventual death in one patient. Two other deaths occurred in the
      perioperative period secondary to cardiorespiratory causes. Three-year primary
      patency, secondary patency, and limb salvage rates were 76%, 90%, and 97%,
      respectively, and progression of infrainguinal disease led to late limb loss in
      two patients. Diabetes as a risk factor was significantly associated with
      decreased primary patency (57% vs 83%; P = .049). Critical ischemia at
      presentation was associated with decreased patency rates as well (P = .002), but
      TASC classification did not significantly alter patency rates. CONCLUSIONS:
      Complex long-segment and bilateral iliac occlusions can be safely treated via
      endovascular means with high rates of symptom resolution. Initial technical
      success, low morbidity, and mid-term durability are comparable to results with
      open reconstruction. A liberal posture to open femoral artery reconstruction
      extends the ability to treat diffuse TASC-C and -D lesions via endovascular
      means.

PMID- 16414385
TI  - The constitutive procoagulant and hypofibrinolytic state in patients with
      intermittent claudication due to infrainguinal disease significantly improves
      with percutaneous transluminal balloon angioplasty.
AB  - BACKGROUND: Patients with intermittent lower limb claudication (IC) exhibit a
      prothrombotic diathesis that is acutely exacerbated by exercise. This may occur
      because of ischemia/reperfusion injury within the leg muscles during walking and
      may contribute to the increased risk of thrombotic vascular events in this group
      of patients. This randomized study compared the effect of lower limb
      revascularization by percutaneous transluminal balloon angioplasty (PTA),
      supervised exercise, and best medical therapy (BMT) alone on this prothrombotic
      state. METHODS: Twenty-three patients (16 men and 7 women; median age, 67 years;
      range, 57-77 years) with IC due to infrainguinal disease were randomized to
      receive BMT alone (n = 7), BMT plus PTA (n = 9), or BMT plus supervised exercise
      (n = 7) as part of the Health Technology Assessment-funded EXercise vs
      Angioplasty in Claudication Trial (EXACT). Patients were assessed at baseline and
      at 3 and 6 months. Thrombin-antithrombin complex (TAT) was determined as a marker
      of thrombin generation, and plasminogen activator inhibitor (PAI) antigen was
      determined as a marker of fibrinolysis. Increased TAT indicates a procoagulant
      state, and increased PAI antigen indicates a hypofibrinolytic state. RESULTS: At
      6 months, subjects randomized to BMT plus PTA demonstrated a significant
      improvement in ankle-brachial pressure index (P = .013) and maximal walking
      distance (P = .008), a significant decline in resting thrombin generation (median
      [interquartile range] TAT, 6.4 microg/L [2.7-13.5 microg/L] to 1.5 microg/L [0.3
      2.9 microg/L]; P = .038), and an improvement in resting fibrinolysis (median
      [interquartile range] PAI-1, 10.0 ng/mL [1.0-20.5 ng/mL] to 1.0 ng/mL [1.0-14.8
      ng/mL]; P = .043). There was no significant change in any of these parameters in
      patients randomized to BMT plus supervised exercise or to BMT alone. CONCLUSIONS:
      The addition of lower limb revascularization by PTA to BMT in patients with IC
      due to infra-inguinal disease results in a medium-term improvement in the resting
      procoagulant and hypofibrinolytic state. This may translate into a reduction in
      morbidity and mortality from thrombotic vascular events in this group of
      patients.

PMID- 16414386
TI  - Simulator assessment of innate endovascular aptitude versus empirically correct
      performance.
AB  - OBJECTIVE: Prior work has established that performance on an endovascular
      simulator incorporating tactile feedback (haptics) correlates with previous
      endovascular experience and can be improved by training. This study was designed
      to test the ability to define and measure innate endovascular aptitude and
      empirically correct performance and to determine whether these are two different
      things. METHODS: Subjects ranging in endovascular skill level from novice to
      expert were surveyed to determine video game experience and skill, endovascular
      level of training, and endovascular experience. They were then tested by using a
      standard protocol requiring timed advancement of a catheter and wire sequentially
      into each of three vessels arising from a simulated type I arch. Recorded trials
      were independently and blindly scored by two experienced endovascular faculty
      members by using a modification of a previously validated scale (Modified Reznick
      Scale; MRS). Summed scores were analyzed by frequency analysis and categorized as
      satisfactory and unsatisfactory on the basis of a clear bimodal distribution.
      Categorical outcome, time to task completion, and other variables were analyzed
      by means of linear regression, analysis of variance, and Welch modified two
      sample t tests, as indicated. RESULTS: A total of 61 subjects were enrolled: 42%
      students, 8% technicians, 19% surgeons, 13% cardiologists, and 18% radiologists.
      Of these, 62% were considered novices and 30% experts on the basis of previous
      experience; 56% of subjects worked in an endovascular-related occupation. MRS
      scores were highly correlated between raters (P < .0001) and showed a clear
      bimodal distribution, with subjects in any endovascular occupation (including
      technicians) scoring significantly better than all others (P < .0001). Hours of
      video games played per week were correlated highly with completion times (P <
      .001) and MRS scores (P < .001). Measures of formal training (number of
      endovascular cases and occupation) correlated highly with completion times (all P
      < .03) and MRS scores (all P < .008). In comparing completion times vs MRS
      scores, three groups were apparent: unskilled-inexperienced, skilled
      inexperienced, and skilled-experienced, corresponding primarily to senior
      subjects without endovascular experience, younger subjects without endovascular
      experience, and formally trained endovascular physicians, respectively. Those
      judged intermediate in aptitude reduced times to the lowest possible level before
      improving their MRS scores. CONCLUSIONS: Although inherently subjective, the MRS
      yields reproducible scores that correlate with endovascular experience and formal
      training. Experts and novices with extensive video game experience achieve short
      completion times, whereas high MRS scores are achieved only by formally trained
      subjects. Innate endovascular aptitude and empirically correct performance may be
      two separate things, and aptitude may be acquirable through (or identified by)
      extensive nonmedical video game experience.

PMID- 16414387
TI  - Decreased wall shear stress in the common carotid artery of patients with
      peripheral arterial disease or abdominal aortic aneurysm: relation to blood
      rheology, vascular risk factors, and intima-media thickness.
AB  - BACKGROUND: Wall shear stress, a local risk factor of atherosclerosis, is
      decreased in the common carotid artery of patients with vascular risk factors. We
      evaluated wall shear stress in the common carotid artery of patients with
      symptomatic peripheral arterial occlusive disease (PAD) and abdominal aortic
      aneurysm (AAA). As blood viscosity is a determinant of wall shear stress, we
      further investigated the impact of rheologic variables on wall shear stress in
      relation to vascular risk factors and intima-media thickness. METHODS: High
      resolution ultrasonography scans were used to study intima-media thickness,
      internal diameter, and blood velocity in the common carotid artery of 31 patients
      with PAD, 36 patients with AAA, and 37 controls. Furthermore, major hemorheologic
      variables and vascular risk factors were evaluated, and wall shear stress was
      calculated. RESULTS: Wall shear stress was lower in patients with PAD (median
      [IQR], dynes/cm(2): 14.4 [10 to 19]) and with AAA (12.1 [9 to 15]) than in
      healthy controls (20.6 [17 to 24]; P < .0001). Wall shear stress was inversely
      related to red cell aggregation (P = .01), fibrinogen (P = .003), leucocyte count
      (P = .001), plasma viscosity (P = .04), and intima-media thickness (P < .0001).
      Furthermore, wall shear stress was negatively associated with age, smoking, and
      triglycerides, but positively correlated with high-density lipoprotein
      cholesterol (all P < .001). When the influence of all these predictors were
      simultaneously taken into account in a multiple regression model, only age (P <
      .0001), smoking (P = .005), and triglycerides (P = .003) remained significantly
      associated with wall shear stress. CONCLUSIONS: This is the first report, to our
      knowledge, showing that wall shear stress of the common carotid artery is
      decreased in patients with symptomatic PAD and in patients with AAA. Rheologic
      variables are less important in predicting wall shear stress than age,
      triglycerides, and smoking.

PMID- 16414389
TI  - Takayasu's arteritis: operative results and influence of disease activity.
AB  - OBJECTIVES: To determine the short- and long-term outcomes of patients treated
      operatively for Takayasu's arteritis and the effect of disease activity on
      results. METHODS: Forty-two (17%) of the 251 patients enrolled in our Takayasu's
      arteritis registry between 1975 and 2002 required operation for symptomatic
      disease. Data were obtained from the registry, patient records, phone
      correspondence, and written surveys. RESULTS: There were 38 females and 4 males
      with a median age of 29 years (range, 12 to 56 years), and 32 (76%) were white.
      Sixty operations were performed for symptomatic disease. The mean duration of
      symptoms before operation was 5.6 months (range, 0 to 25 months). Thirteen (31%)
      patients had active disease and underwent operation for acute presentation or
      failure of medical management. Thirty-nine patients (93%) had operation for
      occlusive disease. Twenty-two (52%) patients had involvement of both the great
      and abdominal aortic branch vessels; 10 (24%) had great vessel disease alone; 9
      (21%) had involvement of abdominal arteries; and 1 (2%) had coronary artery
      disease. There was no operative death, myocardial infarction, major stroke, or
      renal failure. Three patients had early graft thrombosis, two had a minor stroke,
      and two developed hyperperfusion syndrome. The median follow-up was 6.7 years
      (range, 1 month to 19.3 years). Eleven (26%) patients required 15 graft
      revisions; five of the patients had active disease at the time of initial
      operation. All early revisions (<1 year) were in patients with active disease. By
      Kaplan-Meier analysis, freedom from revision at 5 and 10 years was 100% in
      patients with quiescent disease not requiring steroids (group I, n = 5, 12%), 95%
      and 81% in patients whose disease was quiescent on steroids (group II, n = 24,
      57%), 57% in patients with active disease on steroids (group III, n = 7, 17%),
      and 33% in patients with active disease and no long-term steroids (group IV, n =
      6, 14%) (P < .006). The rate of revision or progression of disease at another
      site in 5 years was 0% in group 1, 10% in group 2, 57% in group 3, and 67% in
      group 4 (P < .001) The differences were even more pronounced when an analysis was
      done on the basis of disease activity alone, irrespective of steroid use. During
      the follow-up period, 3 of 39 great vessel, 2 of 18 mesenteric/renal, and 1 of 9
      aortofemoropopliteal reconstructions occluded. The predicted mortality for
      patients was 4% at both 5 and 10 years (95% CI) respectively (confidence interval
      [CI], 0% to 11%) and 10 (CI, 0% to 14%) years, respectively. CONCLUSIONS: The
      minority of patients with Takayasu's arteritis require operation. In our
      predominantly white female patient population, occlusive symptoms were the most
      common indication for operation. Operation for these selected patients was safe,
      with no operative mortality, myocardial infarction, major stroke, or renal
      failure. Patients with active disease requiring operation are more likely to
      require revision or develop progressive symptomatic disease at another site. Long
      term survival is excellent, regardless of disease activity at the time of
      operation.

PMID- 16414390
TI  - Operative and nonoperative management of children aged 13 years or younger with
      arterial trauma of the extremities.
AB  - BACKGROUND: Previous studies have suggested that open repair of arterial injuries
      in very young children often leads to less satisfactory outcomes. The aim of this
      study is to describe a decade's experience in the management of pediatric
      arterial trauma of the limbs, with an additional specific objective to evaluate
      the long-term outcome of arterial traumas in preschool children treated
      conservatively. METHODS: Hospital charts were reviewed for all children aged < or
      =13 years with arterial trauma of the extremities who underwent operative or
      nonoperative treatment. Twenty-three children were located who had arterial
      traumas equally divided between the upper extremity (13) and lower extremity
      (10). RESULTS: The method of treatment was either open surgical repair or medical
      treatment consisting of systematic heparin administration. In 11 of 12 school
      aged children (>6 years; mean age, 10 years), open surgical repair was performed.
      In six of 11 preschool children (< or =6 years; mean, 3.2 years) medical
      treatment was offered. Open repair was deferred in all children <2.5 years.
      Autologous vein interposition grafting was the most common surgical procedure and
      was performed in 10 patients. There were no deaths, and 87% limb salvage (21/23)
      was achieved. Two patients, both in the surgical arm, underwent lower limb
      amputation. The long-term outcome of those treated conservatively was excellent
      in all but one child, in whom minor limb-length discrepancy was detected.
      CONCLUSION: Surgical repair can be performed in school-aged children as in
      adults. Surgical treatment of arterial injuries in neonates, infants, and those
      children <2.5 years old might best be deferred in ischemic but nonthreatened
      limbs. In a nonthreatened ischemic extremity in this age group, systemic
      heparinization is an alternative safe method of management. Limb loss is rare if
      distal Doppler signals are present; but as children grow, limb shortening is a
      threat. In preschool children, the risks of an open surgical repair must be
      weighed against any potential benefits.

PMID- 16414392
TI  - The nonoperative management of penetrating internal jugular vein injury.
AB  - OBJECTIVE: The objective of this study was to review the outcome of nonoperative
      treatment for penetrating internal jugular vein (IJ) injuries in a continuous
      series of prospectively identified, hemodynamically stable patients. METHODS: All
      penetrating neck injuries assessed from February 1, 2004, to August 31, 2004,
      were prospectively identified. Patients without an indication for urgent neck
      exploration underwent diagnostic assessment with multislice helical computed
      tomographic angiography with or without vascular ultrasonography. All IJ injuries
      with no other indication for surgical exploration were treated nonoperatively.
      All patients were discharged home and followed up for a minimum of 1 week to
      document outcomes. RESULTS: From 51 neck injuries penetrating the platysma, 7
      required urgent neck exploration, during which 2 IJ injuries were ligated. Forty
      four patients underwent multislice helical computed tomographic angiography.
      Eight IJ injuries (two gunshot wounds and six stab wounds) with no other
      indication for neck exploration were identified and managed nonoperatively. One
      external wound was in zone 1, five were in zone 2, one was in zone 3, and one
      traversed all three zones. The average length of stay was 4.5 days. At follow-up,
      ranging from 1 week to 5 months, all patients were asymptomatic, and no patient
      required delayed operation for IJ injury. CONCLUSIONS: In hemodynamically stable
      patients with no other indication for exploration, the nonoperative management of
      penetrating jugular vein injuries should be considered as a safe alternative.

PMID- 16414393
TI  - Patient characteristics and physician-determined variables affecting
      saphenofemoral reflux recurrence after ligation and stripping of the great
      saphenous vein.
AB  - OBJECTIVE: To identify patient and physician-controlled treatment variables that
      might predict the persistence or redevelopment of saphenofemoral junction (SFJ)
      reflux. METHODS: Thirteen European centers, with substantial lower extremity
      venous disease practices, examined their experience with SFJ ligation and GSV
      stripping for primary varicose veins in patients followed for > or =2 years,
      entering their data into a protocol-driven matrix that stipulated duplex Doppler
      imaging as an essential component of follow-up examinations and required a
      complete review of all peri-operative examinations, as well as all operative
      procedure and anesthesia notes. Matrix entries were centrally audited for
      consistency and credibility, and queried for correction or clarification before
      being accepted into the study database. Presence or absence of Doppler-detectable
      SFJ reflux was the dependent variable and principal outcome measure. RESULTS:
      Among 1,638 limbs, 315 (19.2%) had SFJ reflux. After adjustment for follow-up
      length and inputting for missing values, multivariable analysis identified seven
      significant predictors. Ultrasonic groin mapping (odds ratio [OR], 0.28; 95%
      confidence interval [CI], 0.20 to 0.40) and <3-cm groin incisions at or
      immediately below the groin crease (OR, 0.50; 95% CI, 0.32 to 0.78) were both
      uniquely associated with diminished probability of follow-up SFJ reflux. Prior
      parity (OR, 2.69; 95% CI, 1.45 to 4.97), body mass index >29 kg/m(2) (OR, 1.65;
      95% CI, 1.12 to 2.43), <3-cm suprainguinal incisions (OR, 3.71; 95% CI, 1.70 to
      5.88), stripping to the ankle (OR, 2.43; 95% CI, 1.71 to 3.46), and interim
      pregnancy during follow-up (OR, 4.74; 95% CI, 2.47 to 9.12), were each
      independent predictors of a greater probability of having SFJ reflux.
      CONCLUSIONS: The findings suggest that ultrasound groin mapping, reticence for
      short suprainguinal or longer groin incisions and extended stripping, and
      counseling women about the effect of future pregnancy are prudent clinical
      choices, especially for obese or previously parous patients.

PMID- 16414394
TI  - Outcome of different endovenous laser wavelengths for great saphenous vein
      ablation.
AB  - OBJECTIVE: The objective of this randomized, prospective, blinded study was to
      determine the relative effects of two laser wavelengths in the treatment of great
      saphenous vein (GSV) insufficiency. METHODS: Fifty-one male and female patients
      scheduled for routine laser treatment of GSV insufficiency provided signed
      informed consent for the procedure. Patients were randomized to receive
      endovenous laser treatment with a wavelength of 810 or 980 nm. The same surgeon,
      blinded to the wavelength, performed all procedures. Nonoperating study staff,
      blinded to the laser wavelengths, evaluated patients before and after the
      procedure regarding physical signs and symptoms. Patients were monitored within
      72 hours after the procedure (via duplex ultrasonography), at 1 week (by
      procedural site photos scored for bruising, as well as a pain score), at 3 weeks,
      and at 4 months for bruising, physical and emotional effects of the procedure
      (scored by patients on a five-point visual analogue scale), and symptoms (scored
      by the physician), along with adverse events. Patients were followed up for a
      year to determine the long-term efficacy of the procedure. RESULTS: The 51
      patients (38 women and 13 men; mean age, 52.4 +/- 11.7 years) completed treatment
      and follow-up examination (30 legs for each wavelength). At 72 hours after the
      procedure, no significant differences were noted between patient outcomes,
      physical conditions, and symptoms and or possible adverse events. At 1 week after
      the procedure, bruising scores were significantly different (P < .005): patients
      in the 980-nm group showed less bruising of the procedure site than the patients
      in the 810-nm group. Only three physical or symptom parameters presented with
      significant differences (P < .05) over time-less itching was noted by 810 nm
      treated patients at 3 weeks after the procedure, lower levels of pain intensity
      were seen in the 980 nm-treated patients at the 4-month follow-up visit, and
      lower varicose vein ratings were seen for the 980 nm-treated patients at the 4
      month follow-up visit. Thirteen legs were phlebitic at 7 days after the procedure
      (10 in the 810-nm group and 3 in the 980-nm group). Two treatment failures
      occurred (one patient in each treatment group); both patients exhibited flow in
      the treated venous segment at the 4-month follow-up visit. Two other patients
      (one in each group) had treatment failure at the 1-year follow-up, demonstrating
      venous insufficiency in the treated segment. CONCLUSIONS: Both laser wavelengths
      were effective in treating GSV insufficiency, with no major complications and a
      paucity of adverse outcomes.

PMID- 16414395
TI  - Efficacy of topical pale sulfonated shale oil in the treatment of venous leg
      ulcers: a randomized, controlled, multicenter study.
AB  - BACKGROUND: Venous leg ulcers are a growing socioeconomic burden. Pale sulfonated
      shale oils (PSSO) are used for therapy of inflammatory skin diseases and have
      been shown to enhance wound healing in vitro and in vivo. The aim of this study
      was to investigate whether PSSO is capable of enhancing venous ulcer healing
      beyond compression therapy alone. METHODS: One hundred nineteen patients were
      enrolled in this randomized, multicenter, observer-blind study. In the treatment
      group, PSSO 10% was applied daily for 20 weeks, and the control group received
      the vehicle only. Wounds were covered by a nonadherent gauze dressing, and
      compression therapy with short-stretch elastic bandages was performed in an
      outpatient setting. The primary study end point was defined as cumulative
      reduction in wound area; the secondary study end point was treatment success as
      assessed by both physicians and patients. Additionally, adverse events, including
      changes with respect to physical examination and vital signs, were documented.
      RESULTS: At the end of the study period, ulcer size was significantly more
      reduced in the PSSO group compared with the vehicle group (15 +/- 15.9 to 6.2 +/-
      12.9 cm(2) vs 11.4 +/- 14.5 to 10.8 +/- 15.7 cm(2); P = .0005). The cumulative
      relative reduction in ulcer area was significantly higher in the PSSO group (
      4391 +/- 4748.7 vs -231.9 +/- 6283.6 % x days; P < .0001). Relative reduction in
      wound area was significantly greater in the PSSO group as early as 6 weeks after
      the beginning of treatment (-47.4 +/- 28.4 vs -23.8 +/- 42.2%; P < .001). PSSO
      was judged successful both by physicians and patients. There were no significant
      differences in adverse events (PSSO, 9 [12.2%]; vehicle, 7 [11.1%]. Similarly,
      tolerability of PSSO was equal to the tolerability of the vehicle. CONCLUSION:
      Pale sulfonated shale oils were capable of favoring venous ulcer healing in
      addition to compression therapy. PSSO should be considered for future wound care
      protocols for treatment of venous leg ulcers.

PMID- 16414396
TI  - Primary Budd-Chiari syndrome: outcome of endovascular management for suprahepatic
      venous obstruction.
AB  - OBJECTIVE: Primary Budd-Chiari syndrome (BCS) is a rare form of hepatic venous
      outflow obstruction at the suprahepatic inferior vena cava (IVC), the hepatic
      veins, or both. We assessed our 4-year experience in the management of BCS to
      evaluate the results of our methods of care. METHODS: We conducted a
      retrospective review of a nonrandomized clinical trial conducted in three
      teaching hospitals. Among 28 primary BCS patients, 9 remained in medical
      treatment only, and 19 who failed to respond to medical treatment received
      additional endovascular (n = 17) or surgical therapy (n = 2). Nine underwent IVC
      balloon angioplasty alone, 6 had angioplasty plus stents, and 2 had transjugular
      intrahepatic portosystemic shunts (TIPS) for hepatic vein lesions. One patient
      had a mesoatrial bypass; another had liver transplantation. Immediate response to
      the therapy was assessed with angiography and ultrasonography based on anatomic
      and/or hemodynamic correction or reduction of the lesion. Subsequent assessment
      of portal hypertension status was made with periodic clinical and laboratory
      evaluation (eg, ultrasonography, liver biopsy). RESULTS: Twenty-six patients had
      had IVC stenosis or occlusion by focal or segmental lesion. Two patients had
      hepatic vein outlet obstruction. There was no evidence of coagulopathy as the
      pathogenesis; all were related to membranous obstruction of the vena cava.
      Excellent immediate response to the endovascular therapy and subsequent relief of
      portal hypertension were achieved in 14 patients. Four patients had restenosis or
      progression of the residual lesion within 2 years; three responded to repeated
      stenting. Primary patency was 76.5%, and primary assisted patency was 94.1%. Two
      patients with TIPS and two with surgical therapy maintained excellent results.
      The medical treatment remained effective only in a limited group of 6 (21.4%) of
      the 28 patients. CONCLUSIONS: In BCS, both endovascular and surgical
      interventions provide excellent results and potentially halt liver parenchymal
      deterioration caused by portal hypertension. Liver transplantation remains the
      ultimate solution for advanced liver failure.

PMID- 16414397
TI  - The development of endotension is associated with increased transmission of
      pressure and serous components in porous expanded polytetrafluoroethylene stent
      grafts: characterization using a canine model.
AB  - OBJECTIVE: This study used a canine model of abdominal aortic aneurysms (AAAs) to
      compare intra-aneurysmal pressure and thrombus formation after exclusion with
      Dacron and expanded polytetrafluoroethylene (ePTFE) stent-grafts. METHODS:
      Prosthetic AAAs with implanted strain-gauge pressure transducers were treated by
      stent-graft exclusion using Food and Drug Administration-approved devices in 10
      mongrel dogs: five Dacron (AneuRx) and five ePTFE (original Excluder). Intra
      aneurysmal pressure was measured over 4 weeks after AAA exclusion and indexed to
      the systemic pressure, represented as a percentage of a simultaneously obtained
      systemic pressure (value = 1.0). Magnetic resonance imaging (MRI) of the intra
      aneurysmal thrombus was performed at 1, 2, and 4 weeks after exclusion and
      expressed as a signal-to-noise ratio (S:N) to control for background signal
      intensity. Comparisons of pressures and S:N between the two stent-grafts was
      analyzed with the Student's t test. Intra-aneurysmal thrombus was characterized
      histologically. RESULTS: In animals excluded with both Dacron and ePTFE stent
      grafts, the intra-aneurysmal pressure was nonpulsatile and reduced to <30% of
      systemic pressure. Significantly greater pressure transmission was observed after
      AAA exclusion using ePTFE compared with Dacron stent grafts (systolic pressure:
      ePTFE, 0.28 +/- 0.12 vs Dacron, 0.11 +/- 0.02, P < .001; mean pressure: ePTFE,
      0.16 +/- 0.08 vs Dacron, 0.06 +/- 0.02, P < .001). MRI confirmed the absence of
      perfusion in all aneurysms. The T1-weighted signal intensity remained
      persistently elevated (S:N at 1 week, 2.7 +/- 0.4 vs 2 weeks, 4.0 +/- 0.2 vs 4
      weeks, 5.4 +/- 1.3) in ePTFE-treated intra-aneurysmal thrombus, suggesting an
      absence of thrombus organization. In contrast, progressive evolution of T1 signal
      intensity in aneurysms excluded by Dacron stent-grafts was consistent with
      maturation from intact red blood cells (S:N at 1 week, 3.3 +/- 0.4) to
      methemoglobin (S:N at 2 weeks, 6.1 +/- 0.8), and then hemosiderin and ferritin
      (S:N at 4 weeks, 2.4 +/- 0.5). Histologically, ePTFE-excluded aneurysms contained
      poorly organized thrombus with red blood cell fragments and haphazardly arranged
      fibrin deposition indicative of active remodeling and continued influx of
      transudated serum. In aneurysms excluded by Dacron stent-grafts, dense, mature
      collagenous connective tissue and organized fibrin were present, indicative of
      greater thrombus organization. CONCLUSIONS: Stent-graft treatment reduces intra
      aneurysmal pressure to <30% of systemic pressure when no endoleak is present;
      however, significantly greater pressure is present in aneurysms treated with
      porous ePTFE stent-grafts than Dacron grafts. Histologic and MRI imaging analysis
      suggest that active transudation of serous blood components may be contributing
      to this increased intra-aneurysmal pressure.

PMID- 16414398
TI  - Simvastatin suppresses experimental aortic aneurysm expansion.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) formation is a result of inflammation
      and extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases
      (MMPs). Hydroxymethylglutaryl-coenzyme A inhibitors (statins), although
      clinically used as lipid-lowering agents, have also been demonstrated to have
      anti-inflammatory effects. This study was designed to determine whether the
      hydroxymethylglutaryl-coenzyme A inhibitor simvastatin suppresses aneurysm
      formation in an elastase-induced rat AAA model. METHODS: Aneurysms were created
      in adult male Wistar rats by infusion of elastase into isolated infrarenal aortic
      segments. The rats were randomized to receive either simvastatin (n = 17) or
      placebo (n = 17) by gastric lavage daily starting the day before surgery. The
      rats were euthanized and the infrarenal aortas harvested on postoperative day 7.
      Aortic diameters were measured before infusion, immediately after infusion, and
      at the time of harvesting. Protein expression was measured by immunoblot
      analysis. Gene expression profiling using Affymetrix U34A rat genome chips was
      performed to identify changes in gene expression caused by simvastatin treatment.
      RESULTS: Mean aneurysm diameter was significantly less in the simvastatin
      treatment group compared with controls (3.4 +/- 0.08 mm vs 4.3 +/- 0.19 mm; P =
      .0001). MMP-9 and nuclear factor-kappaB protein levels were decreased in the
      aortas of simvastatin-treated animals. Gene microarray analysis revealed 315
      genes with statistically significant changes in expression (P < .05) in the
      simvastatin group. Genes related to inflammation, ECM remodeling, and oxidative
      stress function were downregulated. These included genes for interleukin 1,
      interleukin 4, inducible nitric oxide synthase, P-selectin, platelet-derived
      growth factor alpha, tumor necrosis factor, and several chemokines. CONCLUSIONS:
      Simvastatin significantly suppresses experimental aneurysm expansion and reduces
      protein levels of MMP-9 and nuclear factor-kappaB. Gene array analysis provides
      evidence that several mediators of inflammation, matrix remodeling, and oxidative
      stress are downregulated by simvastatin treatment. This suggests that simvastatin
      inhibits AAA formation by blocking the expression of certain proinflammatory
      genes. Simvastatin may be useful as an adjuvant therapy to suppress the growth of
      small aneurysms.

PMID- 16414399
TI  - Increased endogenous angiogenic response and hypoxia-inducible factor-1alpha in
      human critical limb ischemia.
AB  - OBJECTIVE: The potent physiologic endogenous angiogenic response to ischemic
      stimuli is often suboptimal, and therefore, a better understanding of the basic
      mechanisms is essential for the use in therapeutic angiogenesis. Hypoxia
      inducible factor-1 (HIF-1) is a major transcription factor that promotes ischemia
      driven angiogenesis and is induced when the HIF-1alpha subunit is upregulated.
      However, little is known about the endogenous angiogenic response and the role of
      HIF-1alpha in human critical limb ischemia (CLI). We aimed to investigate the
      extent of the angiogenic response and the expression of HIF-1alpha in the lower
      limbs of CLI patients. METHOD: Skeletal muscle biopsy specimens were obtained
      from the lower limbs of 12 patients with CLI and 12 patients without limb
      ischemia (controls), with ethical committee approval. Microvessel density (MVD)
      was determined by using endothelial marker anti-CD31, and HIF-1alpha expressions
      were determined by immunohistochemistry. MVD was measured as the median number of
      microvessels in x200 magnification fields. Five random fields per section and
      three sections per biopsy specimen were analyzed. Enzyme-linked immunoabsorbent
      assay and Western blotting were used to quantify the HIF-1alpha levels.
      Colocalization between cell-specific antigens was investigated by double
      immunofluorescence labelling by using confocal microscopy. Statistical analyses
      were performed with the Mann-Whitney U test. RESULTS: The CLI group have
      significantly higher MVD, with an increase of 2.7-fold compared with the controls
      (P < 0.001). HIF-1alpha expression was significantly increased in CLI muscles (P
      < 0.001) and was localized to vascular endothelial cells. CONCLUSIONS: Our
      findings suggest that the endogenous angiogenic response occurs in CLI. The
      increased HIF-1alpha level and colocalization to vascular endothelial cells
      suggest that HIF-1alpha plays a role in the physiologic endogenous angiogenic
      response in CLI. Therefore, augmentation of the HIF-1alpha pathway may be an
      important aspect in therapeutic angiogenesis.

PMID- 16414400
TI  - The bone marrow-derived endothelial progenitor cell response is impaired in
      delayed wound healing from ischemia.
AB  - OBJECTIVE: Vasculogenesis relies on the recruitment of bone marrow-derived
      endothelial progenitor cells (BMD EPCs) and is stimulated by tissue-level
      ischemia. We hypothesized that the BMD EPC response is impaired in ischemic
      wounds and studied the relationship between BMD EPCs and wound healing. METHODS:
      We used transgenic Tie-2/LacZ mice, which carry the beta-galactosidase (beta-gal)
      reporter gene under Tie-2 promoter control. Wild-type mice were lethally
      irradiated and reconstituted with Tie-2/LacZ bone marrow. Four weeks later, the
      mice underwent unilateral femoral artery ligation/excision and bilateral wounding
      of the hindlimbs. Ischemia was confirmed and monitored with laser Doppler
      imaging. A subset of mice received incisional vs excisional nonischemic bilateral
      hindlimb wounds, without femoral ligation. Excisional wound closure was measured
      by using daily digital imaging and software-assisted calculation of surface area.
      RESULTS: Ischemia resulted in significantly delayed wound healing and
      differentially affected the number of BMD EPCs recruited to wound granulation
      tissue and muscle underlying the wounds. At 3 days postwounding, the granulation
      tissue of the wound base contained significantly fewer numbers of BMD EPCs in
      ischemic wounds compared with the nonischemic wounds (P < .05). In contrast,
      significantly more BMD EPCs were present in the muscle underlying the ischemic
      wounds at this same time point compared with the muscle under the nonischemic
      wounds (P < .05). In ischemic wounds, eventual wound closure significantly
      correlated with a delayed rise in BMD EPCs within the wound granulation tissue
      (Kendall's correlation, -.811, P = .0005) and was significantly associated with a
      gradual recovery of hindlimb perfusion (P < .0001). By 7 days postwounding, BMD
      EPCs were incorporated into the neovessels in the granulation tissue. At 14 days
      and 75 days, BMD EPCs were rarely observed within the wounds. CONCLUSIONS:
      Granulation tissue of excisional ischemic wounds showed significantly less BMD
      EPCs 3 days postwounding, in association with significantly delayed wound
      closure. However, the number of BMD EPCs were increased in ischemic hindlimb
      skeletal muscle, consistent with the notion that ischemia is a powerful signal
      for vasculogenesis. To our knowledge, this is the first report identifying a
      deficit in BMD EPCs in the granulation tissue of ischemic skin wounds and
      reporting the key role for these cells in both ischemic and nonischemic wound
      healing.

PMID- 16414401
TI  - Reduction of myointimal hyperplasia after arterial anastomosis by local injection
      of transforming growth factor beta3.
AB  - BACKGROUND: The transforming growth factor (TGF)-beta family of cytokines exerts
      pleiotropic actions on vascular smooth muscle cell phenotype, proliferation, and
      extracellular matrix synthesis. This in vivo study assessed the use of TGF-beta3
      in attenuating the development of postanastomotic smooth muscle cell
      proliferation. METHODS: Under general anesthesia, 10 adult goats underwent
      transection and reanastomosis of both common carotid arteries. After
      reanastomosis, one artery was infiltrated with 50 ng of TGF-beta3 in 100 microL
      of pH buffer around the anastomosis, and the other side was infiltrated with
      buffer only. After surgery, each animal received 150 mg of aspirin daily. The
      arteries were explanted after 3 months for histologic examination. RESULTS:
      Vessel wall thickness surrounding the anastomosis was reduced by 30% after TGF
      beta3 treatment compared with placebo (P = .003), with a 20% (P = .002) reduction
      in cellular content. Although total collagen content was not significantly
      different between TGF-beta3 and placebo, collagen type VIII content was reduced
      around the TGF-beta3 anastomoses (P = .011). A reduction in the total elastin
      content (P = .003) and number of elastic fiber lamellae (P = .042) was found
      surrounding TGF-beta3-treated anastomoses, but not placebo-treated anastomosis. A
      29% increase in vasa vasorum (P = .044) was present around TGF-beta3-treated
      anastomoses. No differences in inflammatory cell infiltration were seen between
      sides. CONCLUSIONS: Direct subadventitial infiltration of TGF-beta3 immediately
      after creation of an arterial anastomosis attenuates cell proliferation, with a
      reduction in elastin and collagen type VIII content and vessel wall thickness.

PMID- 16414403
TI  - Intraoperative identification of the internal carotid artery: a safety issue.
AB  - The correct intraoperative anatomic identification of the vascular structures in
      the carotid artery bifurcation is important, and in most operations, this is not
      a problem. Experiences with two cases are used to suggest a stepwise system to
      guarantee that anatomic confusion--a confusion that may be fatal--does not occur.

PMID- 16414402
TI  - Bone morphogenetic protein 4: potential regulator of shear stress-induced graft
      neointimal atrophy.
AB  - OBJECTIVE: Placement in baboons of a distal femoral arteriovenous fistula
      increases shear stress through aortoiliac polytetrafluoroethylene (PTFE) grafts
      and induces regression of a preformed neointima. Atrophy of the neointima might
      be controlled by shear stress-induced genes, including the bone morphogenetic
      proteins (BMPs). We have investigated the expression and function of BMPs 2, 4,
      and 5 in the graft neointima and in cultured baboon smooth muscle cells (SMCs).
      METHODS: Baboons received bilateral aortoiliac PTFE grafts and 8 weeks later, a
      unilateral femoral arteriovenous fistula. RESULTS: Quantitative polymerase chain
      reaction showed that high shear stress increased BMP2, 4, and 5 messenger RNA
      (mRNA) in graft intima between 1 and 7 days, while noggin (a BMP inhibitor) mRNA
      was decreased. BMP4 most potently (60% inhibition) inhibited platelet-derived
      growth factor-stimulated SMC proliferation compared with BMP2 and BMP5 (31% and
      26%, respectively). BMP4 also increased SMC death by 190% +/- 10%. Noggin
      reversed the antiproliferative and proapoptotic effects of BMP4. Finally, Western
      blotting confirmed BMP4 protein upregulation by high shear stress at 4 days. BMP4
      expression demonstrated by in situ hybridization was confined to endothelial
      cells. CONCLUSIONS: Increased BMPs (particularly BMP4) coupled with decreased
      noggin may promote high shear stress-mediated graft neointimal atrophy by
      inhibiting SMC proliferation and increasing SMC death.

PMID- 16414404
TI  - Stroke after varicose vein foam injection sclerotherapy.
AB  - This report describes an ischemic stroke after foam injection sclerotherapy of
      varicose veins in a patient with a patent foramen ovale. Foam injection
      sclerotherapy has created resurgence in the minimally invasive treatment of
      varicose veins. The United States Food and Drug Administration halted a clinical
      phase 2 trial of a commercial preparation of polidocanol microfoam in 2003
      because of concerns relating to possible gas embolism. These trials were
      recommenced in July 2005. Neurologic complications such as transient visual
      disturbances and transient confusional states have previously been reported. This
      case, with its strong circumstantial evidence, illustrates the previously
      unconfirmed potential for embolic complications using this technique.

PMID- 16414405
TI  - Successful percutaneous treatment of gluteal claudication secondary to isolated
      bilateral hypogastric stenoses.
AB  - We report an unusual case of bilateral buttock claudication at ambulation of less
      than two blocks in a 57-year-old man with normal lower-extremity segmental
      pressure on noninvasive exercise testing. He was found to have bilateral high
      grade internal iliac artery stenoses on arteriography. Both sides were
      successfully treated in a staged fashion via a contralateral approach with
      percutaneous transluminal angioplasty and a balloon-expandable stent, with
      complete symptom resolution. A clinical vascular examination with normal findings
      of the common iliac, external iliac, and common and superficial femoral arteries
      eliminates significant vascular obstruction as a cause of claudication. However,
      internal iliac occlusive disease may be suspected when symptoms are limited to
      the gluteal musculature and other causes are eliminated. Percutaneous
      interventions can be of diagnostic and therapeutic value.

PMID- 16414406
TI  - Sac enlargement due to seroma after endovascular abdominal aortic aneurysm repair
      with the Endologix PowerLink device.
AB  - A patient who had undergone endovascular repair of an abdominal aortic aneurysm
      with the Endologix PowerLink bifurcated system presented with delayed aortic
      aneurysm enlargement due to assumed endotension. He was treated with aortic sac
      evacuation and wrapping of the endograft. This is the first report of endotension
      and aneurysm sac enlargement after implantation of the PowerLink endograft.

PMID- 16414407
TI  - Progressive growth of a pelvic collection five years after endovascular aneurysm
      repair: an atypical presentation of an asymptomatic contained rupture.
AB  - We report a case of an unusual and late presentation of an asymptomatic contained
      rupture after modular stent-graft implantation to treat an aortobiiliac aneurysm.
      Follow-up computed tomography (CT) scans 4 and 5 years after endovascular
      aneurysm repair showed a homogeneous, nonenhancing, but clearly growing, pelvic
      collection. CT-guided drainage of the collection was performed, and cultures of
      the evacuated brown fluid were negative for any infection. Control CT scan after
      drainage showed a complete collapse of both the collection and the previously
      excluded iliac aneurysms. A direct communication between the sterile pelvic
      collection and the excluded iliac aneurysm was suggested on this CT imaging and
      confirmed afterwards by surgery. From these imaging and surgical findings, this
      pelvic collection can be considered as an atypical presentation of an
      asymptomatic contained rupture of the excluded aneurysm.

PMID- 16414408
TI  - Pneumococcal aortitis: a difficult preoperative diagnosis.
AB  - Primary infections of the aorta are rare. We recently treated a patient who was
      given a diagnosis of noninfectious aortitis after an extensive work-up, but after
      clinical deterioration, was found to have a pneumococcal mycotic aneurysm at the
      time of surgery. The difficulty in distinguishing microbial aortitis from
      noninfectious chronic periaortitis is discussed as well as the need for frequent
      surveillance imaging of the aorta if immunosuppression is used to treat the
      latter entity. The infected aortoiliac segment was ultimately repaired with
      autologous femoral veins.

PMID- 16414409
TI  - Acrylic cement pulmonary embolus masquerading as an embolized central venous
      catheter fragment.
AB  - An acrylic cement pulmonary embolus is a rare complication of percutaneous
      vertebroplasty. Many patients remain completely asymptomatic, but others may
      present with chest discomfort, dyspnea, and even cardiovascular collapse leading
      to death. Here we present an asymptomatic patient initially thought to have a
      central venous catheter pulmonary artery embolus based on the morphology of the
      foreign body on imaging exams. A more thorough investigation established the
      diagnosis of an acrylic cement pulmonary embolus resulting from percutaneous
      vertebroplasty procedures performed many months before the embolus discovery. The
      diagnostic work-up, treatment strategy, and a review of the literature are
      presented.

PMID- 16414410
TI  - Graft-enteric erosion with fungal septic emboli.

PMID- 16414411
TI  - Technique of contemporary iliofemoral and infrainguinal venous thrombectomy.
AB  - Patients with acute deep vein thrombosis involving the iliofemoral venous system
      experience the most severe postthrombotic sequelae. Treatment designed to reduce
      or eliminate the postthrombotic syndrome must necessarily remove thrombus to
      eliminate obstruction. Unfortunately, currently published guidelines do not
      recommend venous thrombectomy and actually recommend against its use because of
      the poor results initially reported. However, recent reports of venous
      thrombectomy and the long-term results of a large randomized trial confirm the
      significant benefit compared with anticoagulation alone. The technique of
      contemporary venous thrombectomy follows basic vascular surgical principles and
      offers patients the opportunity for complete or nearly complete thrombus
      extraction, thereby avoiding the significant morbidity of their anticipated
      postthrombotic syndrome. The techniques described herein represent the authors'
      approach to patients with few alternatives to clear the venous system. Because
      the patient benefit is well established, vascular surgeons should include
      contemporary venous thrombectomy as part of their routine operative
      armamentarium, offering this procedure to patients with extensive deep vein
      thrombosis involving the iliofemoral venous system, especially if other options
      are not available or have failed.

PMID- 16414412
TI  - Consultation or corruption? The ethics of signing on to the medical-industrial
      complex.
AB  - A prominent vascular surgeon is approached by a representative of a large medical
      device company with a proposal to implant a new self-sealing patch for closing
      open carotid endarterectomies. The patch is made of a new synthetic material that
      establishes immediate hemostasis and inhibits restenosis in animal studies. It
      has just been approved for human use by the Food and Drug Administration. The
      cost of the new patch is much higher than for established comparable products,
      even when potential long-term benefits are considered, but using it would reduce
      the operative time required for achieving hemostasis. The manufacturer's
      representative tells you that the company will pay a selected group of vascular
      surgeons $500 apiece each time they insert the patch on their patients and
      complete a one-page report. Surgeons with the highest volume of cases utilizing
      the patch will be offered a paid clinical consultancy with the company. You've
      used another company's product for several years and found it entirely
      satisfactory, but have followed development of the new patch with interest and
      considered trying it in your patients having carotid endarterectomies. What
      should you do? A. Join the study. You probably would have used the new patch on
      your patients anyway. B. If the early data warrant, implant the patch on a trial
      basis without enrolling in the project, and finally decide whether to continue
      using it based on your clinical experience and additional published reports. C.
      Call some of the other investigators who have already enrolled in the project and
      ask them about their experience. D. Decline the invitation immediately. Refuse to
      ever speak to the representative again. E. Estimate the ability of your patients
      to sustain the high cost of the new product and decide accordingly whether to use
      it.

PMID- 16414413
TI  - Regarding "Lifeline registry of endovascular aneurysm repair: long-term primary
      outcome measures".

PMID- 16414414
TI  - Regarding "Limb-salvage angioplasty in vascular surgery practice".

PMID- 16414417
TI  - Differences in individual-level terrorism preparedness in Los Angeles County.
AB  - BACKGROUND: Increasing individual preparedness for disasters, including large
      scale terrorist attacks, is a significant concern of public health planners. As
      with natural disasters, individuals can help protect their health and safety by
      preparing for the emergency situation that may follow a terrorist event. Our
      study describes variations in preparedness among the population of Los Angeles
      County after the September 11, 2001 and subsequent anthrax attacks. METHODS: In
      2004, the data were analyzed from the Los Angeles County Health Survey, a random
      digit-dialed telephone survey of the non-institutionalized population in Los
      Angeles County fielded October 2002 through February 2003. RESULTS: Overall,
      28.0% of respondents had emergency supplies, and 17.1% developed an emergency
      plan in the past year in response to the possibility of terrorism. Factors
      associated with having emergency supplies included African American (adjusted
      odds ratio [AOR] 1.8, 95% confidence interval [CI]=1.1-3.1) and Latino (AOR=1.5,
      95% CI=1.0-2.4) race/ethnicity; having a household dependent aged<or=18 years
      (AOR=1.4, 95% CI=1.0-2.0); being born outside the United States (AOR=1.9, 95%
      CI=1.3-2.9); some college or trade school education (AOR=1.9, 95% CI=1.3-2.9);
      and higher perceived likelihood of a bioterrorist attack (AOR=2.2, 95% CI=1.6
      3.0). Factors associated with having an emergency plan included African American
      (AOR=2.6, 95% CI=1.5-4.6) race/ethnicity; having a household dependent aged<or=18
      years (AOR=2.4, 95% CI=1.6-3.5); and physical disability (AOR=1.7, 95% CI=1.1
      2.7). CONCLUSIONS: Some groups were more likely to adopt some, but not all,
      recommended preparedness activities. Identifying subpopulation differences in
      preparedness is important since different public health messages, programs, and
      distribution channels are required for different subgroups.

PMID- 16414418
TI  - Perceived risk of home fire and escape plans in rural households.
AB  - BACKGROUND: Homes in rural areas have a higher fire death rate. Although
      successful exit from a home fire could greatly reduce fire-related deaths and
      injuries, little is known about factors associated with behaviors of developing
      and practicing an escape plan. METHODS: Between July 2003 and June 2004, a
      baseline survey was administered, in person, to 691 rural households. Information
      collected included a history of previous home fire, perceived risk of home fire,
      existing smoke alarms and their working status, and home fire safety practices,
      as well as home and occupant characteristics. The association of residents'
      perceived risk of home fire and fire escape plans was assessed. RESULTS: Forty
      two percent of rural households reported having a fire escape plan. Of the
      households with a plan, less than two thirds (56.9%) discussed or practiced the
      plan. Households with children were more likely to develop and practice a fire
      escape plan. Households with an elderly or disabled person were less likely to
      develop or practice the plan. Compared to respondents who perceived low or very
      low risk of home fire, those who perceived a high or very high risk had 3.5 times
      greater odds of having a fire escape plan and 5.5 times greater odds of
      discussion or practicing their plan. CONCLUSIONS: Increasing awareness of the
      potential risk of home fires may help occupants develop and practice home fire
      escape plans. In order to reduce fire deaths and injuries, different strategies
      need to be developed for those households in which the occupants lack the ability
      to escape.

PMID- 16414419
TI  - Effects of the Sunny Days, Healthy Ways curriculum on students in grades 6 to 8.
AB  - BACKGROUND: There are few effective sun-safety education programs for use in
      secondary schools. Project aims were to create a sun-safety curriculum for grades
      6 to 8, and to test whether exposure to the curriculum would increase children's
      sun-protection behavior. DESIGN: A pair-matched, group-randomized, pre--post
      test, controlled trial was performed with middle schools as the unit of
      randomization. Teachers implemented the six-unit sun-safety curriculum in 2001
      2003, and analyses were performed in 2003-2004. SETTING/PARTICIPANTS: A total of
      2038 children from 30 middle schools in Colorado, New Mexico, and Arizona. MAIN
      OUTCOME MEASURES: Self-reported sun-protection behavior using frequency ratings
      and diary. RESULTS: Compared to control schools, children receiving the
      curriculum reported more frequent sun protection (p=0.0035), and a greater
      proportion wore long-sleeved shirts during recess (p<0.0001) and applied
      sunscreen (p<0.0001). Exposure to the curriculum improved knowledge (p<0.0001),
      decreased perceived barriers to using sunscreen (p=0.0046), enhanced self
      efficacy expectations (p=0.0577) about sun safety, and reduced favorable
      attitudes toward sun tanning (p=0.0026 to <0.0001). In intent-to-treat analyses,
      the treatment effect was eliminated only under the most conservative assumptions
      about dropouts. CONCLUSIONS: Educational approaches to sun safety in middle
      school may be effective for improving children's sun safety. Potential trial
      limitations include measuring short-term outcomes, focusing on young adolescents,
      using active parental consent, and testing in the American Southwest.

PMID- 16414420
TI  - Nondaily smokers should be asked and advised to quit.
AB  - BACKGROUND: Nondaily smokers are a growing subpopulation of smokers. Current
      cessation guidelines were developed for daily smokers, and how clinicians might
      help nondaily smokers is not clear. METHODS: Analyzing the 2000 National Health
      Interview Survey in 2004, we compared characteristics of nondaily smokers with
      never smokers and daily smokers. We used multivariate logistic regression to
      compare predictors of wanting to quit in 6 months between nondaily and daily
      smokers. RESULTS: About one in five current smokers was a nondaily smoker.
      Nondaily smokers reported better health than daily smokers, but had some health
      status indicators suggesting worse health than never smokers. Nondaily smokers
      were more likely to want to quit (odds ratio [OR]=1.31, 95% confidence interval
      [CI]=1.10-1.56) than daily smokers, but were less likely to report a physician
      having asked about tobacco use (41% vs 50%, p<0.0001) or advised quitting (31% vs
      41%, p<0.0001). In both nondaily and daily smokers, physician advice (nondaily
      OR=1.50, 95% CI=1.03-2.2; daily OR=1.58, 95% CI=1.32-1.89), and the belief that
      secondhand smoke harms others (nondaily OR=1.48, 95% CI=1.04-2.1; daily OR=1.80,
      95% CI=1.56-2.1), predicted wanting to quit. Higher-educated nondaily smokers
      were less likely to want to quit (OR=0.54, 95% CI=0.32-0.91), unlike in daily
      smokers (OR=1.48, 95% CI=1.15-1.89). Latino nondaily smokers were less likely
      (OR=0.43, 95% CI=0.30-0.64) than whites, and African-American daily smokers were
      more likely (OR=1.27, 95% CI=1.04-1.55) than whites, to want to quit.
      CONCLUSIONS: While daily smokers may seem a higher cessation priority, nondaily
      smokers may be more likely to quit with brief interventions. Cessation messages
      should address health risks of any smoking, ethnic differences, smoke-free
      messages, and situational triggers.

PMID- 16414421
TI  - The feasibility of connecting physician offices to a state-level tobacco quit
      line.
AB  - BACKGROUND: Telephone counseling for tobacco cessation is an effective and
      evidence-based approach to address tobacco use. The wide dissemination of region-
      and state-level quit lines has been a major goal for public health agencies.
      However, connecting patients in primary care settings to state-level quit lines
      has not been evaluated. METHODS: Observational study describing two methods (fax
      referral and providing a brochure) to connect private physician offices with a
      state-level quit line in Oregon. This study describes the resources required to
      create a clinical pathway for the 5A's in primary care (ask, advise, assess,
      assist, and arrange) using a state-level telephone quit line as an intervention
      for cessation in primary care clinics sharing a common electronic medical record
      system, focusing on the costs and generalizability of this approach. RESULTS: Of
      the 15,662 smokers identified in 19 primary care clinics, 745 patients were
      referred to the Oregon Tobacco Quit Line during the study period. The program
      cost in the first year was $15 to $22 per patient connected with the quit line;
      in subsequent years, the cost decreased to $4 to $6 per quit-line connection.
      CONCLUSIONS: Connecting private physician offices to a state-level quit line is
      feasible, can be accomplished at low cost with minimal use of resources, and may
      be cost effective. Regional, state, and local tobacco quit lines should consider
      a physician office "quit-line connection" as a practical approach to increase
      utilization.

PMID- 16414422
TI  - The availability and cost of healthier food alternatives.
AB  - BACKGROUND: Many people, especially low-income consumers, do not successfully
      follow dietary recommendations to eat more whole grains and less fat and added
      sugar. The food environment may have a significant impact on the choice by low
      income consumers to eat healthier foods, as both the availability and price of
      healthier food items may limit their ability to eat a healthier diet. We
      investigated the cost and availability of a standard market basket of foods, and
      a healthier basket that included low-fat meat and dairy and whole grain products.
      METHODS: Market-basket surveys were conducted in 25 stores in Los Angeles and
      Sacramento. Stores were selected from neighborhoods that were varied by income
      and surveyed three times from September 2003 to June 2004. The average cost of a
      standard market basket (based on the U.S. Department of Agriculture's Thrifty
      Food Plan [TFP]) and a healthier market basket was calculated from these prices
      and compared using a standard t-test to determine if they were significantly
      different from each other. The analysis was conducted in 2005. RESULTS: In
      neighborhoods served by smaller grocery stores, access to whole-grain products,
      low-fat cheeses, and ground meat with <10% fat is limited. Among all items that
      were unavailable, 64% were in small grocery stores. For the 2-week shopping list,
      the average TFP market-basket cost was $194, and the healthier market-basket cost
      was $230. The average cost of the healthier market basket was more expensive by
      $36 due to higher costs of whole grains, lean ground beef, and skinless poultry.
      The higher cost of the healthier basket is equal to about 35% to 40% of low
      income consumers' food budgets of $2410 a year. CONCLUSIONS: The lack of
      availability in small grocery stores located in low-income neighborhoods, and the
      higher cost of the healthier market basket may be a deterrent to eating healthier
      among very low-income consumers. Public policies should take the food environment
      into account in order to develop successful strategies to encourage the
      consumption of healthier foods.

PMID- 16414423
TI  - Personal, family, social, and environmental correlates of active commuting to
      school.
AB  - BACKGROUND: Active commuting to school may be an important opportunity for
      children to accumulate adequate physical activity for improved cardiovascular
      risk factors, enhanced bone health, and psychosocial well-being. The purpose of
      this study was to examine personal, family, social, and environmental correlates
      of active commuting to school among children. METHODS: Cross-sectional study of
      235 children aged 5 to 6 years and 677 children aged 10 to 12 years from 19
      elementary schools in Melbourne, Australia. Self-administered questionnaires were
      completed by parents, and the older children. The shortest possible routes to
      school were examined using a geographic information system. RESULTS: Among both
      age groups, negative correlates of active commuting to school included parental
      perception of few other children in the neighborhood and no lights or crossings
      for their child to use, and an objectively assessed busy road barrier en route to
      school. In younger children, an objectively assessed steep incline en route to
      school was negatively associated with walking or cycling to school. Good
      connectivity en route to school was negatively associated with walking or cycling
      to school among older children. Among both age groups, children were more likely
      to actively commute to school if their route was <800 meters. There were no
      associations with perceived energy levels or enjoyment of physical activity,
      weight status, or family factors. CONCLUSIONS: For children, creating child
      friendly communities and providing skills to safely negotiate the environment may
      be important. Environmental correlates of active transport in children and adults
      may differ and warrant further investigation.

PMID- 16414424
TI  - Prevalence of the hypertriglyceridemic waist phenotype in Iranian adolescents.
AB  - BACKGROUND: No evidence exists regarding the prevalence of the
      hypertriglyceridemic waist phenotype in adolescents. We aimed to evaluate the
      prevalence of this phenotype in a representative sample of Tehranian adolescents.
      METHODS: Anthropometry and serum triglyceride concentration were assessed in a
      population-based cross-sectional study of 3036 Tehranian adolescents (1413 male
      and 1623 female) aged 10 to 19 years in 1998. Hypertriglyceridemic waist
      phenotype was defined as concurrently having serum triglyceride
      concentration>or=110 mg/dL and waist circumference equal to or greater than the
      90th percentile for age and gender. Overweight (>or=95th percentile) and at risk
      for overweight (>or=85th to <95th percentile) was defined based on the
      standardized percentile curves of body mass index suggested for Iranian
      adolescents. RESULTS: The prevalence of the hypertriglyceridemic waist phenotype
      was 6.4% (95% confidence interval [CI]=5.5-7.2) among Tehranian adolescents
      (males 7.3%, CI=5.9-8.7; females 5.6%, CI=4.4-6.7). When examined by body mass
      index category, 38.7% of overweight adolescents had a hypertriglyceridemic waist
      compared to 7.7% of adolescents at risk for overweight and 0.7% of adolescents at
      normal weight (p=0.001). CONCLUSIONS: This study provides evidence showing that
      the hypertriglyceridemic waist phenotype is prevalent among 6.5% of Tehranian
      adolescents, and particularly among overweight adolescents.

PMID- 16414425
TI  - Parent-child connectedness and behavioral and emotional health among adolescents.
AB  - BACKGROUND: This study sought to examine teen perceptions of mother-child and
      father-child connectedness, with focus on valuing parental opinions and
      perception of parental communication and caring, and associations with behavioral
      and emotional health. METHODS: A population-based sample of 4746 students in
      public schools completed the 2001 Project EAT (Eating Among Teens) survey.
      RESULTS: Overall, the majority of girls and boys reported valuing their parents'
      opinion when making serious decisions and believing that their parents cared
      about them. Yet, one fourth of girls and boys felt unable to talk to their mother
      about problems, and over half of girls and one third of boys felt unable to talk
      to their father. Valuing friends' opinions over parents' opinions, and perceiving
      low parental communication and caring were associated with unhealthy weight
      control, substance use, suicide attempts, body dissatisfaction, depression, and
      low self-esteem. Of significant concern, compared to their peers who reported
      feeling that their mother cared quite a bit or very much, youths who reported
      feeling as though their mother cared very little or not at all about them
      reported particularly high prevalence rates of unhealthy weight control behaviors
      (63.49% girls, 25.45% boys); suicide attempts (33.51% girls, 21.28% boys); low
      self-esteem (47.15% girls, 24.56% boys); and depression (63.52% girls, 33.35%
      boys). CONCLUSIONS: Adolescents' perceptions of low parental caring, difficulty
      talking to their parents about problems, and valuing their friends' opinions for
      serious decisions were significantly associated with compromised behavioral and
      emotional health. Interventions aimed at improving the parent-child relationship
      may provide an avenue toward preventing health risk behaviors in youth.

PMID- 16414426
TI  - Using RE-AIM metrics to evaluate diabetes self-management support interventions.
AB  - BACKGROUND: Current healthcare evidence relies on relatively narrow efficacy data
      to make decisions about program impact. This paper illustrates the application of
      impact indices derived from the RE-AIM (reach, effectiveness, adoption,
      implementation, and maintenance) framework that takes a broader perspective and
      includes issues important to decision makers, such as reach, adoption, and cost.
      METHODS: Composite RE-AIM indices that summarize impact and cost efficiency at
      the individual participant and setting levels are used to compare two different
      diabetes self-management support approaches. One study, the Diabetes Priority
      (DP) program, involved 886 diabetes patients from 30 primary care offices, and
      relied on usual clinical staff for program implementation. The other study,
      Diabetes Health Connection (DHC), involved 335 diabetes patients in both HMO and
      fee-for-service settings, and used health education staff. RESULTS: The DP
      performed better on the setting-level impact index, but the programs produced
      similar results on individual-level impact. The DP had a greater reach (50% vs
      38%); was more effective at the initial follow-up (median effect size [ES]=0.23
      vs 0.17); and had greater impact consistency across various populations. The DHC
      performed better on several indices, including higher physician office adoption
      (20% vs 6%) and staff adoption (79% vs 70%), and there was less variability among
      intervention staff on protocol implementation (median ES=0.0 vs 0.50).
      CONCLUSIONS: Greater use of indices focused on public health and external
      validity criteria could help identify programs most likely to have a meaningful
      impact on population health and to fit local settings and priorities.

PMID- 16414427
TI  - Aspirin use among U.S. adults: Behavioral Risk Factor Surveillance System.
AB  - BACKGROUND: The role of aspirin in prevention of cardiovascular disease (CVD) and
      cardiovascular complications among people with diabetes has been examined. A
      Healthy People 2010 objective calls for increasing the proportion of people with
      diabetes aged>or=40 years who take aspirin>or=15 times per month. METHODS: Data
      from 2003 Behavioral Risk Factor Surveillance System were used to examine (1) the
      prevalence of aspirin intake, (2) aspirin use among those with CVD, (3) aspirin
      use among those with diabetes, (4) current status with respect to Healthy People
      objective 5-16, and (5) changes in aspirin intake from 1999. RESULTS: Daily or
      every-other-day aspirin use was reported by 36.2% of participants in 2003.
      Aspirin intake among those with CVD and diabetes was 82.8% and 62.6%,
      respectively. The Healthy People 2010 objective of increasing the proportion of
      adults with diabetes aged>or=40 years who take aspirin to 30% was achieved. The
      prevalence of aspirin intake was higher in 2003 compared to 1999 among all
      participants, those with CVD, and those with diabetes (relative increase of about
      20%, 12%, and 36%, respectively). Most participants (74%) reported cardiovascular
      reasons for aspirin use. Among those without CVD or diabetes, the prevalence of
      aspirin intake increased with the increasing number of CVD risk factors.
      CONCLUSIONS: Regular aspirin use increased over a 4-year period. Greater use of
      inexpensive and easily accessible interventions to prevent cardiovascular events
      is encouraging. Increased efforts to continue preventive uses of available
      treatment and reduction in risk by modifying other risk factors will help lower
      future disease burden.

PMID- 16414428
TI  - Use of nonprescription medications for perceived cardiovascular health.
AB  - BACKGROUND: Nonprescription products (over-the-counter drugs; vitamins/minerals;
      and nonvitamin, nonmineral supplements) are promoted or advertised for
      cardiovascular health. The extent of nonprescription products used specifically
      for perceived cardiovascular health (NONRX-CVH) is unknown. This study aimed to
      (1) determine prevalence and types of nonprescription medications used for NONRX
      CVH, (2) compare the demographics of NONRX-CVH users to persons using
      nonprescription medications in general, and (3) determine the prevalence of use
      of NONRX-CVH among those taking a prescription medication for a cardiovascular
      reason. METHODS: A cross-sectional survey comprised the probability sample of
      3128 adults in the Minneapolis-St. Paul area in the 2000-2002 Minnesota Heart
      Survey. Trained interviewers collected medication information from participants
      using a structured medication inventory approach. RESULTS: Analysis in 2005 shows
      that 10% of participants (n=315) self-reported taking one or more nonprescription
      medications in the past 2 weeks for a perceived cardiovascular health purpose.
      Among these individuals, prevalence of use of vitamin/mineral supplements,
      nonvitamin/nonmineral supplements, and over-the-counter products for a
      cardiovascular purpose was 37.5%, 21.3%, and 54.6%, respectively. Popular NONRX
      CVHs were aspirin (52.1%), vitamin E (24.4%), garlic (9.8%), and omega-3/fish
      oils/fatty acids (3.8%). NONRX-CVH users were older than general nonprescription
      users (p<0.001). Of 613 people using a prescription drug for cardiovascular
      reasons, 135 (22%) reported using one or more NONRX-CVH medications. CONCLUSIONS:
      Use of NONRX-CVHs, especially aspirin, vitamin E, and herbals, is common, and
      older patients may use aspirin or dietary supplements for this purpose.
      Physicians having patients with cardiovascular disease should ask about
      nonprescription medication usage, as some NONRX-CVHs may be inappropriate.

PMID- 16414429
TI  - Applying lessons from tobacco litigation to obesity lawsuits.
AB  - This discussion examines the use of litigation as a strategy to protect the
      public health. The history of tobacco litigation provides a model to evaluate
      potential litigation strategies against other industries that pose a threat to
      public health, particularly the food industry. This paper demonstrates that
      although legislation would be a preferable solution, lessons from the tobacco
      wars suggest that effective national legislation is unlikely at the present time.
      Based on the differences and similarities between the tobacco and food
      industries, it predicts the effectiveness of particular kinds of obesity
      litigation and the food industry's likely response. The tobacco industry has
      vigorously fought individual injury lawsuits and has had remarkable success in
      resisting such cases. The food industry is likely to successfully employ a
      similar "scorched earth" litigation strategy in individual injury cases. However,
      the tobacco industry did agree to the Master Settlement Agreement in the lawsuits
      brought by the state attorneys general because they were a unique kind of
      litigation with a finite number of plaintiffs. Likewise, state lawsuits under
      consumer protection acts may be a distinct type of litigation that permits cases
      to focus on deceptive advertisements while avoiding complicated causation issues.
      Such lawsuits have the potential to be a useful tool to fight obesity and enlist
      the efforts of the food industry in resisting the epidemic. Understanding the
      lessons of tobacco can save public health advocates much time and many resources
      and thus allow tobacco litigation to benefit public health in new ways.

PMID- 16414430
TI  - Academic health centers and public health departments: partnership matters.
AB  - BACKGROUND: The Institute of Medicine has called for increased population-based
      training for healthcare professions students, and particularly medical students.
      For this to be effective, students should receive such training in the locations
      where population-based approaches to care take place, such as public health
      departments (HDs). However, little is known about currently existing
      relationships between academic health centers (AHCs) and HDs. METHODS: During the
      spring and summer of 2003, e-mail surveys on this topic were sent to the 104
      members of the Association of Academic Health Centers, and 500 members of the
      National Association of City and County Health Officers and the Association of
      State and Territorial Health Officers. Results were received from 50 AHCs and 201
      HDs. RESULTS: Survey results suggest that large numbers of healthcare professions
      students--residents, medical students, and others--are currently being trained in
      many HDs nationwide. The web of relationships between AHCs and HDs extends beyond
      education into research, service, and other purposes. CONCLUSIONS: These
      preliminary results require verification. Nevertheless, they raise questions
      about the types and quality of the education being offered in health departments,
      the impact of AHC/HD relationships on both parties, and how existing
      relationships may be enhanced to meet current and future national needs.

PMID- 16414432
TI  - Building evidence for environmental and policy solutions to prevent childhood
      obesity: the healthy eating research program.

PMID- 16414434
TI  - The multiple layers of prevention science research.

PMID- 16414433
TI  - Linking town and gown.

PMID- 16414435
TI  - Katrina: experiences and education.

PMID- 16414437
TI  - Weighing the evidence: energy determinations across the spectrum of kidney
      disease.
AB  - Evidence based guidelines for medical nutrition therapy (MNT) in chronic kidney
      disease (CKD) recommend a range of caloric levels, dependent on age and level of
      kidney function. Recent literature has explored whether current research findings
      still support these earlier conclusions, and if new energy determinations for CKD
      are warranted. This review will take a brief look at the history of the
      controversy, examine the research evidence at the time of practice guideline
      development, investigate emerging research, and discuss implications for
      additional scientific inquiry.

PMID- 16414436
TI  - Muscle protein metabolism during hemodialysis.
AB  - Despite improvement in many aspects of the care of maintenance hemodialysis (HD)
      patients, protein-calorie malnutrition, which is characterized by an insidious
      loss of somatic protein, is common and is a major risk factor for increased
      morbidity and mortality. We present here an overview of the current knowledge on
      protein metabolism in uremic patients with the expectation of providing insights
      into the mechanisms involved in HD-associated catabolism and outlining the
      rationale underlying intradialytic nutrition. We concentrate on the discussion of
      muscle protein metabolism because muscle is the predominant site of protein
      storage, and its integrity is mandatory for the maintenance of a good quality of
      life.

PMID- 16414438
TI  - Nutritional parameters and mortality in incident hemodialysis patients.
AB  - OBJECTIVE: To evaluate the impact of nutritional parameters at the time of
      initiation of hemodialysis (HD) on mortality. DESIGN: Retrospective study.
      SETTING: Dialysis Unit of the Federal University of Sao Paulo, Oswaldo Ramos
      Foundation. PATIENTS: Three hundred forty-four incident HD patients (60.5% male,
      26% diabetic) with the first nutritional evaluation performed before completing 3
      months of onset of HD were included. METHODS: The study consisted of baseline
      measurements of several nutritional parameters (triceps skinfold thickness [TSF],
      midarm muscle circumference [MAMC], body mass index [BMI], serum albumin, serum
      creatinine, and protein and energy intake assessed by 3-day food diary) and
      records of outcome (death) over a period of 10 years. RESULTS: Muscle and/or fat
      depletion was observed in 51% of the studied patients, according to the percent
      standard of MAMC and TSF, respectively. Presence of diabetes, age over 60 years,
      serum albumin < 3.5 g/dL, MAMC adequacy < 90%, protein intake < 1.0 g/kg/d, and
      energy intake < 25 kcal/kg/d were associated with worse survival. When patients
      were analyzed according to tertiles of dialysis vintage, BMI > or = 25
      (calculated as kg/m2) had a negative impact on survival only in the highest
      tertile (> 2.45 years). Patients with BMI < 25 and MAMC adequacy > or = 90%
      showed the best survival over the study period, and those with BMI > or = 25 but
      MAMC adequacy < 90% had the worst survival (P = .004). In the multivariate
      survival analysis adjusting for diabetes, advanced age, and hypoalbuminemia, the
      reduced MAMC (P = .008) and the low energy intake (P = .03) were independent
      predictors of death in incident HD patients. CONCLUSIONS: Reduced MAMC and low
      energy intake at the beginning of chronic dialysis are risk factors for
      mortality. A negative effect of high BMI on survival was associated with reduced
      MAMC and longer dialysis vintage.

PMID- 16414439
TI  - Effect of boiling on dietary phosphate and nitrogen intake.
AB  - OBJECTIVE: Dietary phosphate restriction is one of the means of phosphatemia
      control in dialysis patients. To limit dietary phosphate intake, appropriate food
      choices are recommended, but this often creates a conflict with the high-normal
      protein requirement of dialysis patients. Although food processing by boiling may
      be a safe tool for eliminating many minerals, this method poses a risk for loss
      of important nutrients, including proteins. The goal of this study was to assess
      the effect of boiling on phosphate and protein nitrogen changes in commonly used
      foods that contain proteins of high biological value. METHODS: We evaluated the
      true retention values of dry matter, crude protein, and total phosphorus in fresh
      beef and chicken breast before and after 10, 20, and 30 minutes of boiling; the
      reported values represent the average of five determinations. RESULTS: Compared
      with crude raw samples, dry matter retention in cooked beef was reduced up to 92%
      +/- 6%, crude protein retention was reduced up to 87% +/- 10%, and phosphorous
      retention was reduced up to 42% +/- 13%; similar data were obtained when boiling
      the chicken breast, 93% +/- 3%, 81% +/- 4%, and 63% +/- 6%, respectively.
      CONCLUSIONS: Our results show that consuming boiled foods can significantly
      reduce dietary phosphate while preserving protein intake, namely reducing the
      effective phosphate intake per gram of dietary protein. This can represent
      additional advice to the patient for limiting the dietary phosphorus load at the
      same protein intake, leading to a better control of phosphate balance together
      with a lower risk of protein malnutrition.

PMID- 16414440
TI  - Calcium exposure and removal in chronic hemodialysis patients.
AB  - The risks associated with calcium exposure in chronic hemodialysis (HD) patients
      are becoming increasingly apparent. Current K/DOQI guidelines recommend an
      absolute maximum elemental calcium load of 2,000 mg/d, including calcium
      containing medication and a maximum dialysate calcium concentration of 1.25
      mmol/L (to avoid intradialytic calcium loading). The goal of this study was to
      characterize the total exposure to calcium from all sources that chronic HD
      patients are exposed to. We studied 52 patients. Each was requested to complete a
      3-day food diary for analysis of daily calcium intake; 24-hour urine collections
      were taken and analyzed for calcium content. All patients underwent HD using
      Hospal Integra (Lyon, France) dialysis monitors, bicarbonate buffering, and
      dialysate sodium and calcium concentrations of 134 mmol/L and 1.25 mmol/L,
      respectively. Blood was sampled before and after HD for total serum calcium,
      albumin, bicarbonate, and phosphate, in addition to ionized calcium level
      measured at the bedside using a portable electrolyte analyzer. Calcium flux was
      determined from measurements of ionized calcium levels in dialyzer inlet samples
      and those in continuous partial waste dialysis collection (with reference to
      total waste dialysate and ultrafiltration volumes). There was marked interpatient
      variability of total calcium exposure; the mean was 2,346 +/- 293 mg (range, 230
      to 7,309 mg) per day. The majority of enteral calcium exposure was from calcium
      containing phosphate binders, with diet providing only a mean load of 581 +/- 34
      mg (range, 230 to 1,309 mg). Calcium removal was evident in 83% of patients. Mean
      calcium flux was -187 +/- 232 mg (range, -486 to 784 mg). There was a linear
      correlation observed between the amount of calcium removed during dialysis and
      the predialysis ionized plasma calcium concentration, r2 = 0.42, P < .001
      (calculated from actual measured dialysate ionized calcium concentration). This
      shows that calcium flux across the dialysis membrane is determined by the
      diffusion gradient. The amount of calcium removed during dialysis was found to be
      independent of exogenous calcium load. These results support previous reported
      data showing that the majority of HD patients are continually experiencing
      calcium overload. This may have a contributory role in the development of
      vascular calcification. In contrast to recent K/DOQI recommendations, an upper
      dialysate concentration of 1.25 mmol/L may not be ideal for every patient. To
      minimize the effects of exogenous calcium overload, dialysate concentrations
      should be prescribed with reference to plasma calcium levels.

PMID- 16414441
TI  - Impact of convective flow on phosphorus removal in maintenance hemodialysis
      patients.
AB  - OBJECTIVE: Hyperphosphatemia leads to increased risk of death in maintenance
      hemodialysis patients (MHD). This study investigated phosphorus (P) removal, P
      reduction rate (PRR), and P rebound, comparing on-line, high-volume
      hemodiafiltration in postdilution (HDF) and high-flux hemodialysis (HD) in a
      setting of an equal amount of produced dialysate solution in both modalities.
      METHODS: A total of 22 MHD patients, treated with regular 3 x 4 hours HDF weekly,
      were randomly dialyzed with one 4-hour session of HDF and of HD. In both
      modalities, an equal amount of produced dialysate solution of 800 mL/minute was
      used. The only variable was the fact that in HDF, 100 mL/min of this produced
      dialysate solution was used as replacement fluid. The other parameters were kept
      identical: blood flow rate, 350 mL/min; high-flux polysulfone F80 dialyzer; and
      4800 E monitor, (Fresenius, Bad Homburg, Germany). The P removal was measured in
      total spent dialysate and ultrafiltrate volumes. Statistical analyses were done
      with the paired t-test. RESULTS: The mean total P removed with HDF was 1159 +/-
      296 mg, and 972 +/- 312 mg with HD (P < .001), ie, 19% higher in HDF; PRR was
      significantly higher in HDF (63.3%) versus HD (58.6%) (P = .014). The mean serum
      P did not differ: 5.3 mg/dL in HDF and 5.2 mg/dL in HD. There was a linear
      correlation between serum P and P removal. With a serum P level up to 5 to 5.5
      mg/dL, HDF achieved a higher P removal compared with HD. The difference gradually
      decreased as the serum P value increased. Above 7 mg/dL, no difference in total P
      removal was observed. There was a high but equal rebound percentage at 60 minutes
      in HDF (42%) and HD (39%) (P = .42). With HDF, no predialysis metabolic acidosis
      was noted. CONCLUSIONS: Treatment with on-line HDF in postdilution resulted in a
      higher P removal and higher PRR compared with HD. The long-term implementation of
      this modality may result in a more optimal serum P control, without an increase
      in the number of or lengthening of the dialysis sessions.

PMID- 16414442
TI  - Nutritional status and food insecurity in hemodialysis patients.
AB  - OBJECTIVE: The purpose of this study was to determine whether a relationship
      exists between nutrition status and food security of patients on hemodialysis
      (HD). DESIGN: A descriptive correlation study. SETTING: This study consisted of
      HD patients undergoing treatment at three northeast Louisiana dialysis centers.
      PATIENTS: Ninety-eight HD patients participated in the study. The mean age of
      subjects was 59.1 +/- 14.2 years. The sample was 44% white and 56% black; 49%
      male and 51% female. RESULTS: Multiple linear regression and chi2 analysis were
      used to assess relationships between demographics and food insecurity scores and
      Subjective Global Assessment scores. Race significantly predicted food insecurity
      (beta = 0.248; P = .019), with black patients being more food insecure than white
      subjects. A significant positive relationship was found between the level of
      education and Subjective Global Assessment scores (beta = 0.222; P = .037). In
      this sample, 16.3% of the subjects were found to be food insecure, and 64.3% of
      the patients were mildly to moderately malnourished, whereas another 13.3% were
      severely malnourished. CONCLUSIONS: Future research in this area should include
      food security questions related to the ability to obtain foods for health. Renal
      health care professionals should assess patients for possible food insecurity so
      that appropriate interventions can be implemented.

PMID- 16414443
TI  - A simple nutrition screening tool for hemodialysis nurses.
AB  - OBJECTIVE: To assess the reliability of a nurse-performed nutrition screening
      tool (NST) for hemodialysis (HD) patients to identify nutritionally at-risk
      patients. DESIGN: Tool reliability assessment. SETTING AND PARTICIPANTS: The
      setting was nine non-hospital private (n = 3) and public (n = 6) HD units in
      Australia (two rural and seven metropolitan). Participants were 112 HD patients.
      RESULTS: A total of 112 HD patients (male = 65, female = 47) from 9 non-hospital
      HD units in Australia (seven metropolitan and two rural) were screened with the
      NST and the outcome of dietitian referral compared with Standard Dietitians
      Assessment. The mean age of patients was 57.6 years. Overall, the NST showed a
      sensitivity of 0.84 (range, 0.71 to 0.94; P < .05) and a specificity of 0.9
      (range, 0.82 to 0.98; P < .05). The NST was more sensitive (sensitivity, 0.93
      [range, 0.87 to 0.99; P < .05]) and was more specific for men (specificity, 0.92
      [range, 0.85 to 0.99; P < .05]). Specificity was very strong in metropolitan
      patients (specificity, 0.94 [range, 0.87 to 1.01; P < .05]). CONCLUSIONS: The
      tool was more sensitive and specific than the NST previously reported by the same
      investigators. The tool is particularly specific in that it screens those
      patients not requiring dietitian intervention. The use of this tool may benefit
      HD units that do not have on-site or regular dietetic support to prioritize
      patients needing dietitian intervention.

PMID- 16414444
TI  - The impact of Super Bowl parties on nutritional parameters among hemodialysis
      patients.
AB  - BACKGROUND: Little is known about the impact of holiday and other special-event
      meals on patients with chronic medical conditions. It is possible that patients
      are less adherent with dietary restrictions during such meals. We sought to
      determine the impact of Super Bowl parties on nutritional parameters among
      hemodialysis patients. OBJECTIVE: To determine the relationship between attending
      a Super Bowl party and subsequent change in serum phosphorus level, serum
      potassium level, interdialytic weight gain, and blood pressure. DESIGN:
      Retrospective cohort study. SETTING: Outpatient dialysis unit. PATIENTS: One
      hundred twenty-two chronic hemodialysis patients. MAIN OUTCOME MEASURES: Patients
      were asked whether they had attended a Super Bowl party. Serum phosphorus level,
      serum potassium level, interdialytic weight gain, and predialysis blood pressure
      at the hemodialysis treatment after the Super Bowl and at the hemodialysis
      treatment 1 month previously were obtained by chart abstraction. RESULTS: The 15
      patients who had attended a party had increased serum phosphorus levels (+0.5
      mg/dL) and interdialytic weight gain (+1.1% of dry weight) from baseline. These
      increases were statistically significant (P values .005 and .02, respectively)
      compared with patients who did not attend a party. Attendees also had increased
      systolic blood pressure (+6 mm Hg) from baseline, but this was of marginal
      statistical significance compared with nonattendees (P = .14). Attending a party
      was not significantly associated with changes in serum potassium and diastolic
      blood pressure. CONCLUSIONS: Attending a Super Bowl party is associated with
      adverse changes in several nutritional parameters. Although patients should not
      be discouraged from attending holiday and special-event meals, management of
      hemodialysis patients should include increased dietary counseling before holidays
      and special events and increased monitoring afterward.

PMID- 16414445
TI  - Fermentable carbohydrate supplementation alters nitrogen excretion in chronic
      renal failure.
AB  - BACKGROUND: Considerable attention has been given to the impact of nutrition on
      kidney disease. Most dietary attempts to treat chronic renal failure (CRF) and to
      decrease uremia use a protein restriction. An alternative dietetic approach based
      on fermentable carbohydrate (FC) supplementation of the diet could lead to the
      same urea-lowering effect by increasing urea nitrogen (N) excretion in stool,
      with a concomitant decrease of the total N quantity excreted in urine. METHODS:
      In the present prospective study, the impact of FC (40 g/d) on uremia and on N
      excretion routes was investigated during 5 weeks in nine CRF patients in the
      presence of a moderated restrictive protein diet (0.8 g/kg/d). Patients were
      their own controls and were treated by the cross-over method after randomization
      (5 weeks with FC versus 5 weeks without FC). RESULTS: Feeding FC significantly
      increased the quantity of N excreted in stool from 2.1 +/- 0.8 to 3.2 +/- 1.1 g/d
      (+51%) (P < .01) and decreased, in parallel, the urinary N excretion from 9.4 +/-
      1.7 to 8.3 +/- 1.4 g/d (-12%) (P < .01). The total N quantities excreted by the
      two routes were unchanged by the FC, which shows that the FC was efficient to
      shift N excretion from the urinary route toward the digestive route. As a result
      of the increase of urea transfer into the colon, the plasma urea concentration
      was significantly decreased from 26.1 +/- 8.7 to 20.2 +/- 8.2 mmol/L (-23%) (P <
      .05). CONCLUSIONS: These results show the same beneficial effects in CRF as those
      obtained with a restrictive protein diet without its nutritional drawbacks. This
      should be confirmed by other prospective works over a longer duration and a
      larger number of patients to study the effects of FC on CRF progression and on
      CRF terminal stage tolerance.

PMID- 16414446
TI  - Targeting your patient's preferred learning style.

PMID- 16414447
TI  - Patient education. Enhanced foods: hidden phosphorus and sodium in foods commonly
      eaten.

PMID- 16414448
TI  - Care of the kidney transplant recipient.

PMID- 16414449
TI  - Toronto porcine stentless valve and the need for something more.

PMID- 16414450
TI  - Effects of oxidized and glycated low-density lipoproteins on transcription and
      secretion of plasminogen activator inhibitor-1 in vascular endothelial cells.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of
      fibrinolysis. Elevated levels of PAI-1 were frequently detected in patients with
      coronary artery disease (CAD) or diabetes. Low-density lipoprotein (LDL) is a
      classical risk factor of CAD. Oxidation and glycation increase the atherogenecity
      of LDL. Previous studies demonstrated that oxidized LDL (oxLDL) or glycated LDL
      (gly-LDL) increased the release of PAI-1 from endothelial cells (ECs). The
      present study examined the effects of oxLDL and gly-LDL on the transcription,
      expression, secretion, and subcellular distribution of PAI-1 in cultured human
      ECs. Treatment with LDL significantly increased the promoter activity, mRNA
      level, and the release of PAI-1 from ECs by two- to threefold compared to
      controls. Oxidation or glycation significantly enhanced the effects of LDL on PAI
      1 production in ECs compared to LDL (four- to fivefold vs. controls). No
      significant differences were detected between the effects of oxLDL and gly-LDL.
      Abundant PAI-1 antigens were detected in the perinuclear region of ECs and
      overlapped with giantin, a marker of Golgi apparatus. Treatment with brefeldin A
      disturbed the stack structure of Golgi apparatus and almost completely inhibited
      the release of PAI-1 from ECs induced by the lipoproteins and at basal
      conditions. The results suggest that oxidation and glycation enhanced the effects
      of LDL on the production of PAI-1 in ECs through increasing the transcription of
      PAI-1. Intact Golgi apparatus is required for PAI-1 generation from ECs induced
      by LDL or its modified forms.

PMID- 16414451
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia: is there a role for
      viruses?
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a primary
      heart muscle disease characterized structurally by progressive fibrofatty
      replacement of the right ventricle and clinically by life-threatening ventricular
      arrhythmias with left bundle branch block morphology. Recently, there has been a
      great deal of interest on ARVC/D as a cause of sudden death in young people, and
      it has been reported as the most common cause of exercise-related sudden death
      among competitive athletes in Italy. An autosomic dominant familial occurrence
      has been recognized, and four disease-causing genes have been recently identified
      in the dominant forms: ryanodinic cardiac receptor 2, desmoplakin, plakophilin 2,
      and transforming growth factor (TGF)-beta3. Furthermore, plakoglobin has been
      identified as the first gene responsible for the recessive variant of ARVC/D
      associated with palmoplantar keratosis and woolly hair (Naxos disease). However,
      although much progress has been made in molecular genetics, up to today, the
      pathogenesis of the disease is still unclear. The occurrence of myocyte apoptosis
      has been documented, suggesting that recurrent bouts of apoptosis may account for
      progressive atrophy of the myocardium, which is then replaced by fibrofatty
      tissue. Considering the frequent finding of myocarditis at histology, an
      inflammatory theory has been advanced, and infective mechanisms have been
      postulated to contribute to the onset and the progression of the disease.
      Cardiotropic viruses have been detected in some ARVC/D cases, and they have been
      proposed as possible etiologic agents. Several etiopathogenetic theories are
      herein presented in detail with particular attention to the
      inflammatory/infective one and its possible links between this and the
      genetic/dystrophic theories are discussed.

PMID- 16414452
TI  - QT interval dispersion in patients with chronic heart failure secondary to
      Chagas' cardiomyopathy: correlation with clinical variables of prognostic
      significance.
AB  - BACKGROUND: QTc interval dispersion has rarely been studied in patients with
      chronic heart failure (CHF) secondary to Chagas' cardiomyopathy. One study has
      demonstrated an association between QT interval dispersion and sudden cardiac
      death. No data exist regarding the association of clinical variables and QT
      interval dispersion in patients with this condition. METHODS: Sixty three
      patients with CHF due to Chagas' cardiomyopathy, 34 Chagas' disease patients with
      no systolic dysfunction on echocardiography, and 36 individuals with no previous
      cardiac history, matched by sex and a 10-year age interval, were included in the
      investigation. The QTc interval dispersion was defined as the difference between
      maximum and minimum QTc. RESULTS: The mean QTc interval dispersion was 74+/-30.3
      ms in surviving and 87+/-30.6 ms in nonsurviving patients (P=.13). Mean QTc
      dispersion was 95.20+/-28.46 ms in patients who died from pump failure, 73.33+/
      29.61 ms in patients who died suddenly, and 74.46+/-30.27 in survivors (P=.07).
      Mean QTc dispersion value was higher in patients in the Class III or IV
      (P=.01).). Mean QTc interval dispersion was 67.2+/-22.7 ms in patients with and
      85.5+/-33.5 ms in patients without premature ventricular contractions (P=.01),
      and 67.5+/-29.8 ms in patients with and 84.7+/-31.8 ms in patients without left
      ventricular apical aneurysm (P=.03). A correlation could be observed in QTc
      interval dispersion and left atrium dimension (r=.32; P=.009) Thus, QTc interval
      dispersion is associated to some prognostic indicators in patients with CHF
      secondary to Chagas' cardiomyopathy.

PMID- 16414454
TI  - Congenital heart defects in siblings with partial aneuploidy of chromosome 2p.
AB  - Cytogenetic anomalies are found in 13% of children with congenital heart disease,
      providing positional information that may aid in identifying genes governing
      cardiac development. We report two children born to a clinically normal female
      with a balanced chromosomal rearrangement, resulting from insertion of 2p24.2
      p25.1 into chromosome 1. Each of her offspring had complex congenital heart
      disease, including left ventricular hypoplasia, and inherited a different copy
      number of the 2p segment. These findings suggest that proper dosage of a gene or
      genes in this region is important in normal cardiac development.

PMID- 16414453
TI  - Periostin and periostin-like factor in the human heart: possible therapeutic
      targets.
AB  - BACKGROUND: Although numerous signaling pathways have been identified in adult
      heart disease, our ability to diagnose and treat human cardiomyopathies remains
      limited. A family of proteins, which includes periostin and periostin-like factor
      (PLF), has been identified during heart development and disease. Based on recent
      findings, these proteins are candidate therapeutic agents for heart disease.
      METHODS: Affymetrix GeneChip Expression Analysis as well as northern and western
      blot analyses were used to determine periostin and PLF expression in humans.
      Periostin-like factor levels were determined, by western blot analysis, in the
      rat animal model used to study myocardial loading and unloading. In vivo and in
      vitro effects of overexpressing PLF by infection with adenovirus were assessed by
      calculating cardiac myocyte cross-sectional area and determining the level of
      protein synthesis, respectively. RESULTS AND CONCLUSIONS: Our findings on PLF
      suggest that this periostin isoform plays a crucial role in adult cardiac myocyte
      growth following mechanical overload, thus, implicating its potential as a
      therapeutic target. In addition, we believe that the differences between the
      periostin and PLF are of functional significance.

PMID- 16414455
TI  - CD117-positive cells and mast cells in adult human cardiac valves--observations
      and implications for the creation of bioengineered grafts.
AB  - BACKGROUND: There is no report to date of stem cells in human cardiac valves. We
      examined their possible presence, number, and distribution in valves removed at
      cardiac surgery from patients with a variety of underlying valve pathologies.
      METHODS: Grossly normal aortic and mitral valves were obtained from live heart
      transplant patients. Surgically excised valves with rheumatic mitral stenosis,
      aortic valve age-related degeneration, aortic valve changes of aortoannular
      ectasia, and mitral valves with myxomatous degeneration were studied.
      Immunohistochemical and histochemical studies were performed on sequential valve
      sections, including hematoxylin and eosin, hematoxylin phloxine saffron, Movat
      pentachrome, toluidine blue, CD31, CD34, and CD117. RESULTS: There were small
      clusters of CD117-positive cells in the fibrosa and spongiosa of mitral and
      aortic valves from all groups of valves. Sequential sectioning and staining
      showed that almost all of these cells were mast cells. However, in the mitral
      myxomatous valves and the mitral rheumatic valves, there were rare CD117-positive
      cells that did not have corresponding toluidine blue staining and thus could be
      valve mesenchymal stem cells. CONCLUSIONS: Most of the CD117-positive cells in
      normal and diseased adult heart valves are mast cells. These valve cells could
      play a role in valve pathology and injury. A very small number of possible valve
      stem cells were also identified. It is unlikely that these valve stem cells are
      sufficient in number to allow isolation and expansion for tissue engineering
      purposes.

PMID- 16414456
TI  - Morphological findings in explanted Toronto stentless porcine valves.
AB  - BACKGROUND: Stentless porcine valves have many documented advantages over stented
      valves. Since its introduction in 1991, the Toronto stentless porcine valve (T
      SPV) has shown excellent hemodynamic performance. METHODS: A total of 332 T-SPVs
      have been implanted at our institution up to December 2003, 25 of which have been
      explanted at surgery. Herein, we report a study of 30 explanted T-SPVs seen at
      our institution over a 5-year period. RESULTS: The mean patient age at explant
      was 61.2+/-11.8 years with a mean implant duration of 100.7+/-27.8 months (after
      excluding one valve removed early postoperatively for infective endocarditis).
      Twenty-seven of 30 valves (90%) showed structural deterioration characterized by
      tissue degeneration, cusp tears, calcification, and lipid insudation. Eight
      valves (26.7%) showed evidence of calcification on gross inspection and a total
      of 23 valves (76.7%) showed at least one microscopic focus of calcification,
      located primarily in the basal and commissural regions of the cusp. Twenty valves
      (66.6%) showed cusp tears. Pannus was visible grossly on the surface of 27 of 30
      valves (90%), while histologically, at least some degree of pannus was observed
      on both the inflow and outflow surfaces of all but two valves. Twelve T-SPV
      (40.0%) showed calcification in the porcine aortic tissue, four of which involved
      calcification of the porcine muscle shelf in the right coronary cusp. Two T-SPV
      showed no significant structural deterioration. Their clinical reason for
      explantation was incompetence or infective endocarditis. CONCLUSION: With a
      freedom from reoperation of about 87.0% at up to 10 years, the T-SPV shows
      excellent durability. The majority of explanted valves show structural valve
      deterioration similar to that seen in other porcine heart valves.

PMID- 16414458
TI  - Tuberculoma of the heart.

PMID- 16414457
TI  - Pathology of coronary narrowing after arterial switch operation: autopsy findings
      in two patients who died within 3 months of surgical treatment and review of the
      literature.
AB  - The arterial switch operation (ASO) has become the surgical treatment of choice
      for transposition of the great arteries (TGA). Myocardial ischemia owing to
      coronary complication remains the commonest cause of mortality and morbidity
      following ASO. The main clinical manifestations of coronary obstruction reported
      after a switch procedure are heart failure, arrhythmias, or sudden death.
      Coronary complications are responsible for about 50% of early death and for
      almost all late deaths. We describe pathologic and anatomic findings in two cases
      of late sudden death after an ASO. Critical intimal thickening and acute take-off
      of coronary trunks were the main pathological substrates of death. Histological
      examination revealed an obstructive coronary proliferation characterised by a
      concentric stratum of intimal smooth muscle cell hyperplasia with preserved
      tunica media. Pathogenetic assessment of intimal coronary lesions after an ASO
      should consider the role of endothelium and vascular parietal wall in the
      unavoidable response to injury caused by arterial reconstruction. Since a rapidly
      progressive proliferative disease is suspected, to explain coronary narrowing,
      understanding endothelial biology and improving surgical technique should help to
      prevent late coronary events.

PMID- 16414459
TI  - Cardiac angiosarcoma.
AB  - Primary tumors of the heart are extremely rare, with a prevalence rate of around
      0.01% in collective autopsy studies. Majority of the primary cardiac tumors are
      benign. Myxoma is the most common primary cardiac tumor, while angiosarcoma is
      the commonest primary malignant tumor. We present a case report of a 20-year-old
      patient with history of breathlessness and hemoptysis. A malignant mass was seen
      arising in the right atrium, with pericardial effusion and multiple metastases in
      the lung. A complete autopsy was performed and a diagnosis of cardiac
      angiosarcoma was confirmed on histology and immunohistochemistry.

PMID- 16414461
TI  - Augmented subscapularis muscle transposition for rotator cuff repair during
      shoulder arthroplasty in patients with rheumatoid arthritis.
AB  - The effectiveness of rotator cuff repair by augmented subscapularis transposition
      via the Leeds-Keio artificial ligament was evaluated in patients with rheumatoid
      arthritis undergoing total shoulder arthroplasty. The minimum follow-up period
      was 2 years. Final clinical scores (Hospital for Special Surgery scoring system)
      and the incidence of radiolucency and upward migration of shoulder components in
      20 shoulders with rotator cuff repair by augmented subscapularis transposition
      were superior to those of 19 shoulders with cuff repair by subscapularis
      transposition alone and similar to those of 22 shoulders with intact rotator
      cuffs. In shoulders with augmented subscapularis transposition and intact cuffs,
      clinical scores continued to improve even after the first postoperative year. Our
      augmented subscapularis transposition did not increase postoperative
      complications. We conclude that cuff repair by augmented subscapularis
      transposition is an acceptable alternative for repairing a supraspinatus or
      supraspinatus and infraspinatus rotator cuff defect in rheumatoid arthritis
      patients undergoing total shoulder arthroplasty.

PMID- 16414462
TI  - The efficacy of ultrasound in the diagnosis of long head of the biceps tendon
      pathology.
AB  - The use of shoulder ultrasound as an imaging modality has recently gained
      widespread attention; however, the ability of ultrasound to diagnose long head of
      the biceps tendon pathology accurately still remains unclear. The biceps tendons
      in 71 patients were prospectively evaluated by comparison of standard
      ultrasonographic and arthroscopic examinations. Arthroscopic examination was used
      as the gold standard comparison. Ultrasound showed a 100% specificity and 96%
      sensitivity for subluxation or dislocation. Ultrasound detected all complete
      ruptures of the biceps tendon but detected none of the 23 partial-thickness
      tears. Overall, ultrasound diagnosed 35 of 36 normal biceps tendons (specificity,
      97%) and 17 of 35 abnormal biceps tendons (sensitivity, 49%). Ultrasound can
      reliably diagnose complete rupture, subluxation, or dislocation of the biceps
      tendon. It is not reliable for detecting intraarticular partial-thickness tears.

PMID- 16414463
TI  - Effectiveness of replacement arthroplasty with calcar grafting and avoidance of
      greater tuberosity osteotomy for the treatment of humeral surgical neck
      nonunions.
AB  - A retrospective review was conducted on 12 patients (mean age, 63 years)
      undergoing replacement arthroplasty with calcar grafting for humeral surgical
      neck nonunions. Patients were evaluated preoperatively for pain and range of
      motion and postoperatively by use of the American Shoulder and Elbow Surgeons and
      Constant scores. Indications included severe pain, disability, humeral head
      destruction, and inadequate bone stock. Nine patients were available for a mean
      of 69 months' follow-up. Eight underwent humeral head replacement, and one
      underwent total shoulder replacement. None required greater tuberosity osteotomy.
      Previously, open reduction-internal fixation had failed in 2 and closed reduction
      and percutaneous pinning had failed in 1. Calcar grafts were incorporated in 7 of
      9 patients. Postoperative pain was absent in 7 and mild in 2. Mean active forward
      elevation improved by 64 degrees . Mean active external rotation improved by 45
      degrees . Postoperatively, American Shoulder and Elbow Surgeons scores averaged
      80 and Constant scores averaged 64. Replacement arthroplasty with calcar grafting
      is a reliable treatment option for surgical neck nonunions.

PMID- 16414464
TI  - Complications of total shoulder arthroplasty: are they fewer or different?
AB  - There has been significant evolution of total shoulder arthroplasty design and
      improvement in technique over the past 25 years, but there is no information
      available as to whether this has translated into lower complication rates or
      different sorts of complications. The purpose of this study was to determine the
      contemporary complications and their frequency. Between 1990 and 2000, 431 total
      shoulder arthroplasties were performed with a cemented all-polyethylene glenoid
      component. Follow-up averaged 4.2 years. Complications were categorized by type
      as early or late and as minor, major, or major requiring reoperation. In total,
      53 surgical complications occurred in 53 patients (12%). Of these, 32 were major
      complications (7.4%), with 17 of these requiring reoperation. Index complications
      in order of frequency included rotator cuff tearing, postoperative glenohumeral
      instability, and periprosthetic humeral fracture. Notably, glenoid and humeral
      component loosening requiring reoperation occurred in only 1 shoulder. Developing
      a complication was unrelated to diagnosis, previous surgery, age, sex, humeral
      head size, or cementing or not cementing the humeral component. Data from the
      contemporary patient group suggest that there are fewer complications of shoulder
      arthroplasty and less need for reoperation. Especially striking is the near
      absence of component revision because of loosening or other mechanical factors.
      Periprosthetic humeral fractures are more common; the explanation for this
      warrants further study.

PMID- 16414465
TI  - Osteoarthritis in shoulders with traumatic anterior instability: preoperative
      survey using radiography and computed tomography.
AB  - The purposes of this report are to determine the incidence of preoperative
      osteoarthritis in shoulders with traumatic anterior instability and to detect the
      factors leading to its development. The radiographs and computed tomograms of
      shoulders in 282 patients with unilateral instability and without previous
      surgery, whose age was younger than 40 years and who had no possibility of
      nontraumatic secondary osteoarthritis, were examined by use of a simplified
      modification of Samilson and Prieto's criteria. Osteoarthritis was found in 32
      joints (11.3%) (mild in 30 and moderate in 2) on the radiographs. Computed
      tomography (CT) revealed arthritic changes in 88 shoulders (31.2%), including all
      32 radiographically osteoarthritic joints. The marginal spur of the humeral head
      initially occurred in the anteroinferior aspect and mainly extended downward. The
      total number of dislocations and/or subluxations and frequency of dislocation
      and/or subluxation of 32 radiologically osteoarthritic joints were significantly
      larger and higher, respectively, than those of 194 non-osteoarthritic joints (P <
      .02). The total number of dislocations and/or subluxations (P < .01) and the
      number of subluxations (P < .05) were significantly different between
      osteoarthritic joints and nonarthritic joints classified by CT findings. The rate
      detected by CT was higher than those of any other previous radiographic survey
      that may have underestimated the incidence rate. Most postoperative
      osteoarthritis cases recognized on radiographs in short-term or midterm follow-up
      studies are assumed to be preoperatively generated.

PMID- 16414466
TI  - Deficits in shoulder function and general health associated with sixteen common
      shoulder diagnoses: a study of 2674 patients.
AB  - The purpose of this study is to define the self-assessed deficits in function and
      general health perceived by a large cohort of patients with common shoulder
      diagnoses. For a 10-year period, all new shoulder patients presenting to the
      senior author were characterized by diagnosis, age, gender, and self-assessed
      shoulder function and general health status. This report concerns the 2674
      patients having 1 of the 16 most prevalent diagnoses. The deficits in shoulder
      function and health status were correlated with diagnosis, age, and gender, as
      well as with each other. Patient self-assessment provided a standardized method
      for collecting data on shoulder function and health status. These assessments
      revealed substantial deficits; for example, 81% of patients were unable to sleep
      on the affected side, and 71% were unable to wash the back of the opposite
      shoulder. The magnitude of these deficits correlated significantly with gender
      and diagnosis but not with age.

PMID- 16414467
TI  - In vivo anatomy of the Neer and Hawkins sign positions for shoulder impingement.
AB  - The Neer and Hawkins impingement signs are commonly used to diagnose subacromial
      pathology, but the anatomy of these maneuvers has not been well elucidated in
      vivo. This 3-dimensional open magnetic resonance imaging study characterized
      shoulder anatomy and rotator cuff impingement in 8 normal volunteers placed in
      the Neer and Hawkins positions. Subacromial and intraarticular contact of the
      rotator cuff was graded, and minimum distances were computed between the tendon
      insertion sites and the glenoid, acromion, and coracoid. Both the Neer and
      Hawkins maneuvers significantly decreased the distance from the supraspinatus
      insertion to the acromion and posterior glenoid and from the subscapularis
      insertion to the anterior glenoid. However, the Hawkins position resulted in
      significantly greater subacromial space narrowing and subacromial rotator cuff
      contact than the Neer position. In the Hawkins position, subacromial contact of
      the supraspinatus and infraspinatus was observed in 7 of 8 and 5 of 8 subjects,
      respectively. In contrast, rotator cuff contact with the acromion did not occur
      in any subject in the Neer position. Intraarticular contact of the supraspinatus
      with the posterosuperior glenoid was observed in all subjects in both positions.
      Subscapularis contact with the anterior glenoid was also seen in 7 of 8 subjects
      in the Neer position and in all subjects in the Hawkins position. This extensive
      intraarticular contact suggests that internal impingement may play a role in the
      Neer and Hawkins signs.

PMID- 16414468
TI  - Shoulder arthroplasty in Olmsted County, Minnesota, 1976-2000: a population-based
      study.
AB  - Because little information is currently available on the epidemiology of shoulder
      arthroplasty, this study was designed to evaluate the characteristics of patients
      undergoing this procedure and changes in practice patterns. Residents of Olmsted
      County, Minnesota, who underwent shoulder arthroplasty between 1976 and 2000 were
      identified (98 residents, 112 procedures). A relatively lower initial rate of
      shoulder arthroplasty was followed by a statistically significant steady increase
      (P < .0001), with an age- and sex-adjusted annual operative incidence rate of 1.4
      per 100,000 person-years (1976-1980) to 10.1 per 100,000 person-years (1996
      2000). Increased utilization of shoulder arthroplasty during the last decade was
      mainly a result of its application in osteoarthritis. A significant need exists
      for examination of utilization patterns for shoulder arthroplasty. An aging
      population and an increased demand and awareness by the public regarding
      interventions to improve quality of life will shape the future of arthroplasty,
      reinforcing the need for future studies of this nature.

PMID- 16414469
TI  - A comparison of magnetic resonance imaging findings of the acromioclavicular
      joint in symptomatic versus asymptomatic patients.
AB  - The purpose of this study was to compare acromioclavicular (AC) joint magnetic
      resonance imaging (MRI) findings in asymptomatic patients with those in
      symptomatic patients. The MRI scans of 25 patients with symptomatic AC joints
      were compared with 50 asymptomatic control subjects by use of the same grading
      scale. In the symptomatic group, AC joint arthritis grading was normal in 0%,
      mild in 20%, moderate in 52%, and severe in 28%. In the asymptomatic group,
      grading was normal in 18%, mild in 66%, moderate in 12%, and severe in 4%; there
      was a statistically higher grade of AC arthritis in the symptomatic group (P <
      .05). Of the symptomatic individuals, 80% demonstrated reactive bone edema in
      either the distal clavicle (6), the acromion (3), or both sides of the AC joint
      (11), whereas no individual in the asymptomatic group had this finding (P < .05).
      Reactive bone edema on MRI is a more reliable predictor of symptomatic AC
      pathology than degenerative changes seen on MRI and, when correlated with
      clinical examination, is reproducible.

PMID- 16414470
TI  - Operative treatment of the painful sternoclavicular joint: a new technique using
      interpositional arthroplasty.
AB  - This study presents the results of a new surgical technique, resection of the
      medial end of the clavicle and interposition of the sternal head of the
      sternocleidomastoid muscle, that was used for the treatment of 17 painful
      sternoclavicular (SC) joints, 14 of which were available for review. The etiology
      of the pain was primary or posttraumatic degenerative arthritis in 10, osteitis
      condensans in 2, and SC joint infection in 2. The results of surgery, evaluated
      with the Rockwood SC joint rating scale and examination of the patients, were
      determined at a mean follow-up of 46 months. Results were excellent in 4
      shoulders, good in 6, fair in 3, and poor in 1. All of the fair and poor results
      occurred in workers' compensation patients. Interposition arthroplasty performed
      in conjunction with resection of the medial clavicle proved to be a safe and
      effective method of treatment for the painful, degenerative or septic SC joint.

PMID- 16414471
TI  - Loss of total arc of motion in collegiate baseball players.
AB  - Published studies on asymptomatic athletes show an increase in external rotation
      and decrease in internal rotation while maintaining the total arc of motion of
      the glenohumeral joint. The purpose of this study was to determine whether
      overhand athletes with shoulder pain maintained their total arc of motion. Sixty
      seven college-level baseball players were examined. Internal rotation and
      external rotation of the glenohumeral joint, measured at 90 degrees of abduction,
      and total arc of shoulder motion were compared between dominant and nondominant
      extremities in athletes with and without shoulder pain. Dominant shoulders in the
      pain group had a mean arc of 136.2 degrees compared with 145.8 degrees in the
      nondominant group, for a side-to-side difference of 9.6 degrees. We demonstrate
      that college-level baseball players with shoulder pain have a significant
      decrease in total arc of shoulder motion and internal rotation compared with
      their nondominant shoulder and with pain-free athletes.

PMID- 16414472
TI  - Posterior shoulder pain in throwing athletes with a Bennett lesion: factors that
      influence throwing pain.
AB  - A Bennett lesion is a bony spur at the posterior glenoid that is often seen in
      baseball players and usually asymptomatic. However, it sometimes becomes painful,
      but the mechanism of throwing pain is still unknown. The purposes of this study
      were to identify clinical characteristics associated with the Bennett lesion
      causing shoulder pain (painful Bennett lesion) and to try to predict which type
      of Bennett lesion might become painful. Several clinical factors in 51
      consecutive baseball players who underwent arthroscopic surgery were
      investigated. Of these baseball players, 24 had a bony spur: 13 were diagnosed as
      having a painful Bennett lesion and 11 were diagnosed as having an asymptomatic
      Bennett lesion, according to our previously reported criteria. The other 27
      players did not have a bony spur. Posterior joint laxity, no deficit of internal
      rotation, and an avulsed fragment on computed tomography scan were determined to
      be the characteristic clinical features in the shoulders with a painful Bennett
      lesion.

PMID- 16414473
TI  - Rotator cuff repair after shoulder replacement.
AB  - Development of a rotator cuff tear after shoulder arthroplasty can adversely
      affect outcome. To assess the results of a subsequent procedure to repair the
      torn cuff, we reviewed all shoulder arthroplasties performed at our institution
      to identify patients who had a subsequent operation for cuff repair with or
      without component revision. We identified 19 patients and 20 involved shoulders.
      One patient was lost to follow-up, and one was excluded because the subsequent
      cuff repair could not be adequately accomplished. Patients were studied
      retrospectively a mean of 9.1 years after cuff repair by analysis of
      prospectively collected data supplemented by use of a questionnaire (10
      shoulders). The presence of the tear was diagnosed preoperatively by physical
      examination or routine radiographs in 13 shoulders, an arthrogram in 3, and
      surgical exploration in 2. The tear involved the subscapularis in 7 shoulders,
      the supraspinatus in 15, and the infraspinatus in 8. Rotator cuff repair was
      successful in only 4 shoulders and was unsuccessful in the remaining 14. Pain was
      absent in 4 shoulders, slight in 6, occasionally moderate in 5, and moderate in
      3. The mean visual analog pain score was 5.6. Range of motion was limited, with
      mean values for elevation of 78 degrees and external rotation of 54 degrees .
      Because results of subsequent cuff repair are poor, every attempt should be made
      to repair the cuff securely and carefully direct postoperative physical therapy.

PMID- 16414474
TI  - Treatment of glenoid loosening and bone loss due to osteolysis with glenoid bone
      grafting.
AB  - Twenty-four patients underwent conversion of a total shoulder replacement to a
      humeral head replacement with glenoid bone grafting for glenoid loosening due to
      osteolysis. Of the 24 patients, 18 (75%) had satisfactory pain relief at a mean
      follow-up of 33.4 months (range, 24-63 months). Four had good pain relief with
      conversion back to total shoulder replacement at a mean of 11 months (range, 9-15
      months) after the index procedure, thus bringing the rate of overall satisfactory
      pain relief to 92%. Two patients continued to report significant pain and were
      not satisfied with the procedure. Significant functional motion improvements were
      not seen (P > .05). Graft subsidence was seen in 10 of 20 cases (50%). Bone
      grafting of glenoid defects in revision arthroplasty provides satisfactory
      improvement in terms of pain relief and, by improving bone stock, allows for
      placement of a glenoid component at a later date if there is persistent pain.
      However, high rates of graft subsidence are concerning.

PMID- 16414475
TI  - Locking mechanism failure in semiconstrained total elbow arthroplasty.
AB  - Between 1988 and 2000, we performed 170 total elbow replacements using a
      semiconstrained implant (custom or standard). We are aware of 9 implants (5.3%)
      that have had late failure of the locking mechanism, as evidenced by migration of
      the connecting axle on radiographic examination. The mean time to failure of the
      locking mechanism was 5.5 years. Eight elbows required surgery for revision of
      the polyethylene bushing and locking mechanism by use of a custom-made locking
      clip. A limited approach was devised that allowed sufficient exposure to change
      the bushing and axle. In 1 of the 8 cases, the revised locking mechanism failed
      at 5.5 years, necessitating a reoperation. Of the 8 patients, 7 have not had
      recurrence of the failure at a mean of 1.4 years (minimum follow-up of 1 year).
      These 7 patients have good or excellent results based on the Hospital for Special
      Surgery elbow scoring system, with a mean arc of motion of 130 degrees.

PMID- 16414476
TI  - Comminuted olecranon fractures: a comparison of plating methods.
AB  - The relative strength of posterior plating and dual medial-lateral plating for
      comminuted olecranon fractures has not been evaluated. Fifteen male cadaveric
      elbows with simulated highly comminuted olecranon fractures were tested to
      failure via cantilever bending. The strength of dual medial-lateral plates and a
      single posterior plate with and without an intramedullary screw was evaluated.
      The mean bending moment at failure for the dual-plated specimens was 30.0 +/- 7.5
      Nm. The mean bending moment at failure for specimens with a posterior plate
      without an intramedullary screw was 34.5 +/- 9.1 Nm. The mean bending moment at
      failure for specimens with a posterior plate and an intramedullary screw was 44.5
      +/- 6.9 Nm; this was significantly greater than for dual-plated specimens (P <
      .05) but not for specimens with a posterior plate without an intramedullary
      screw. The posterior plate with an intramedullary screw was the most stable
      construct tested and may, therefore, be the preferred method of fixation for
      comminuted olecranon fractures. This construct was significantly (48%) stronger
      than dual medial and lateral plating.

PMID- 16414477
TI  - Stress distribution in the supraspinatus tendon with partial-thickness tears: an
      analysis using two-dimensional finite element model.
AB  - The purpose of this study was to clarify the stress distribution in the rotator
      cuff tendon with 3 types of partial-thickness tears by use of 2-dimensional
      finite element analysis. In the finite element model of the normal human
      shoulder, a tendon defect was created on the articular surface, on the bursal
      surface, or in the midsubstance close to the insertion. A tensile force was
      applied to the proximal end of the tendon, and the stress distribution was
      calculated. In all 3 types of tears, a high stress concentration appeared around
      the articular surface at the insertion and at the site of the tear, which
      extended proximally. The maximum value of the von Mises stress increased with the
      presence of a partial-thickness tear. With the arm in abduction, a high stress
      concentration was also observed around the site of the tear. These biomechanical
      conditions of the supraspinatus tendon may eventually lead to a full-thickness
      tear at the critical zone.

PMID- 16414478
TI  - The effect of cementing technique on structural fixation of pegged glenoid
      components in total shoulder arthroplasty.
AB  - Although loosening of cemented glenoid components is one of the major
      complications of total shoulder arthroplasty, there is little information about
      factors affecting initial fixation of these components in the scapular neck. This
      study was performed to assess the characteristics of structural fixation of
      pegged glenoid components, if inserted with two different recommended cementing
      techniques. Six fresh-frozen shoulder specimens and two types of glenoid
      components were used. The glenoids were prepared according to the instructions
      and with the instrumentation of the manufacturer. In 3 specimens, the bone cement
      was inserted into the peg receiving holes (n = 12) and applied to the back
      surface of the glenoid component with a syringe. In the other 3 specimens, the
      cement was inserted into the holes (n = 15) by use of pure finger pressure: no
      cement was applied on the backside of the component. Micro-computed tomography
      scans with a resolution of 36 microm showed an intact cement mantle around all 12
      pegs (100%) when a syringe was used. An incomplete cement plug was found in 7 of
      15 pegs (47%) when the finger-pressure technique was used. Cement penetration
      into the cancellous bone was deeper in osteopenic bone. Application of bone
      cement on the backside of the glenoid prosthesis improved seating by filling out
      small spaces between bone and polyethylene resulting from irregularities after
      reaming or local cement extrusion from a drill hole. The fixation of a pegged
      glenoid component is better if the holes are filled with cement under pressure by
      use of a syringe and if cement is applied to the back of the glenoid component
      than if cement is inserted with pure finger pressure and no cement is applied to
      the back surface of the component.

PMID- 16414480
TI  - Operative treatment of chronic Monteggia lesion in younger children: a report of
      three cases.

PMID- 16414479
TI  - Rotator cuff regeneration using chitin fabric as an acellular matrix.
AB  - Twenty-one rabbits were used to investigate the feasibility of using nonwoven
      chitin fabric as an acellular matrix for rotator cuff regeneration. Infraspinatus
      tendons were cut bilaterally to create 10 x 10-mm defects. The defect in the
      right shoulder was covered with chitin fabric. The contralateral defect was left
      free as a control. The specimens were evaluated histologically and
      immunohistochemically at 2, 4, 8, and 12 weeks and biomechanically at 12 weeks
      after surgery. The acellular matrix increased cell numbers and improved collagen
      fiber alignment. The regenerated tissues were composed of type III collagen. The
      structural properties of the grafted shoulder were significantly greater than
      those of the control. This study revealed that using chitin fabric as an
      acellular matrix has advantages in enhancing both biologic and mechanical
      regeneration of rotator cuff tendons.

PMID- 16414481
TI  - Recurrent infection of the rotator cuff after open repair: case report.

PMID- 16414482
TI  - Reconstruction of the proximal half of the radius using vascularized fibula:
      significance of soft-tissue reconstruction.

PMID- 16414483
TI  - Schwannoma of the suprascapular nerve: a case report.

PMID- 16414484
TI  - Acute triceps ruptures: case report and retrospective chart review.

PMID- 16414485
TI  - Robotic prostatectomy: is it the future?

PMID- 16414486
TI  - Rationale for zoledronic acid therapy in men with hormone-sensitive prostate
      cancer with or without bone metastasis.
AB  - Men with prostate cancer are at risk for bone loss and skeletal complications
      throughout the course of their disease. Bone loss is prevalent in many men with
      prostate cancer at initial diagnosis, and initiating androgen deprivation therapy
      results in accelerated bone resorption, leading to bone loss and an increased
      risk of fracture. These men are also at high risk for disease progression and
      bone metastases that can result in significant skeletal morbidity, including
      pathologic fracture, spinal cord compression, and debilitating bone pain
      requiring additional therapy. Excessive osteoclast activity plays a central role
      in the pathophysiology of bone disease at each stage of prostate cancer disease
      progression. Zoledronic acid, a highly potent inhibitor of osteoclast-mediated
      bone resorption, has increased bone mineral density in men receiving androgen
      deprivation therapy and is the only bisphosphonate that has shown statistically
      significant reductions in skeletal morbidity in patients with bone metastases
      from prostate cancer. Furthermore, preclinical evidence suggests that zoledronic
      acid has antitumor activity in prostate cancer models. Recently, a treatment
      algorithm was developed by the 3rd International Consultation on Prostate Cancer
      recommending the use of zoledronic acid for the prevention of skeletal
      complications in patients with bone metastases from prostate cancer, regardless
      of their hormone status, and for the prevention of treatment-induced bone loss in
      patients without evidence of bone metastases. According to this algorithm,
      zoledronic acid should be considered for the prevention of skeletal morbidity in
      patients with prostate cancer throughout their treatment continuum.

PMID- 16414487
TI  - Long-term results of primary adenocarcinoma of the urinary bladder: a report on
      192 patients.
AB  - OBJECTIVES: To evaluate the clinical presentation and treatment end results of
      primary adenocarcinoma of the urinary bladder, and to determine the significant
      independent prognostic factors that determine this outcome. PATIENTS AND METHODS:
      Of 3659 patients who underwent cystectomy, 192 had adenocarcinoma of the urinary
      bladder, with a relative frequency of 5.2%. Most of these patients (68.2%)
      presented in late stages (P3 + P4). The incidence of pelvic lymph nodes
      involvement was 25.5%. Mucinous adenocarcinoma was reported in 28 patients
      (14.6%), papillary in 20 (10.4%), signet ring in 14 (7.3%), while not otherwise
      specified was reported in 130 (67.7%) in the cystectomy specimens. RESULTS:
      Mucinous and signet-ring histologic subtypes showed increased frequency of high
      stages and high grades, and more nodal involvement than the papillary and not
      otherwise specified. All patients were treated with radical cystectomy and pelvic
      lymphadenectomy with (69 patients) or without (123) postoperative radiotherapy.
      The 5-year disease-free survival rate was 46 +/- 4% for all patients with
      adenocarcinoma. Postoperative radiotherapy improved the disease-free survival
      significantly. The 5-year disease-free survival rate for the postoperative
      radiotherapy group was 61 +/- 6% compared to 37 +/- 5% for the cystectomy alone
      group (P = 0.002). Local control rate was significantly improved from 53 +/- 7%
      for cystectomy alone to 96 +/- 3% for postoperative radiotherapy patients (P =
      0.00001). Distant metastases were the leading cause of death in the postoperative
      radiotherapy group. CONCLUSIONS: Within the limitations provided by retrospective
      studies, it could be concluded that postoperative radiotherapy improved the
      disease-free survival through its effect on local control. The disease-free
      survival independent prognostic variables were tumor stage, postoperative
      radiotherapy, nodal involvement, and adenocarcinoma subclassification. These
      factors, except the adeno-subclassification, were also found to determine the
      local control rate. On the other hand, the independent prognostic factors for
      distant metastasis were lymph nodal involvement, stage, and adeno
      subclassification.

PMID- 16414488
TI  - Impact of a genetic variant in CYP3A4 on risk and clinical presentation of
      prostate cancer among white and African-American men.
AB  - Genes involved in androgen metabolism are strong candidates for having an
      important role in the pathogenesis of prostate cancer. CYP3A4, a protein in the
      cytochrome P-450 supergene family, facilitates the oxidative deactivation of
      testosterone. In previous studies, patients with the G variant of a genetic
      polymorphism in CYP3A4 had prostate cancers with clinically aggressive
      characteristics at diagnosis. The association was strongest among elderly men. We
      investigated whether the CYP3A4 variant was linked with the diagnosis or clinical
      presentation of prostate cancer in a case control study of a multiethnic urban
      population. Biologic specimens were genotyped for CYP3A4, and analyzed for the
      impact of this genotype on risk and tumor characteristics at presentation,
      controlling for the effect of several cofactors. The CYP3A4 variant was more
      common among African-Americans than among white men. Race-stratified analyses
      revealed little association between the CYP3A4 variant and prostate cancer risk
      among white men but were limited by the small number of white men with the CYP3A4
      variant. Of African-American men, while the variant G allele was not associated
      with prostate cancer that had less aggressive characteristics, it was associated
      with risk of aggressive prostate cancer when men with the AG genotype (odds ratio
      = 9.3, 95% confidence interval 1.3-411) or GG genotype (odds ratio = 11.9 95%
      confidence interval 1.6-533) were compared with those with the AA genotype. The
      association between the CYP3A4 genotype and aggressive prostate cancer in African
      American men is consistent with findings of other studies.

PMID- 16414489
TI  - Health related quality of life outcomes after radical prostatectomy: attention to
      study design and the patient-based importance of single-surgeon studies.
AB  - OBJECTIVE: To define accurately health related quality of life outcomes in men
      undergoing radical prostatectomy (RP) by a single surgeon. MATERIALS AND METHODS:
      Since September 1999, men undergoing RP were asked to complete the Medical
      Outcomes Study Short Form-36 (SF-36) and University of California Los Angeles
      Prostate Cancer Index preoperatively, returning it to a third party data center.
      Anonymous surveys were mailed to each patient at 1 and 2 years. RESULTS: We
      captured 90% and 82% of men at 1 and 2 years, respectively. Mean scores in the SF
      36 domains and bowel function/bother were unchanged from preoperative at 1 and 2
      years. Urinary function and bother scores were lower at year 1, but stable at
      year 2. Men wearing > or = 1 pad/d scored significantly lower in urinary function
      and bother than those noted as pad-free. Pad-free rates were 82% at year 1 and
      89% at year 2. Sexual function and bother scores were significantly lower at
      years 1 and 2. In men younger than 60 years with unilateral nerve-sparing
      surgery, at 2 years, 50% had erections adequate for intercourse. CONCLUSIONS:
      This single-surgeon outcomes study after RP showed stability in the SF-36 and
      bowel domains to 2 years. At 2 years, the vast majority of men were pad-free
      (89%), and the majority of young men after unilateral nerve-sparing surgery had
      erections adequate for intercourse (50%). Accurate outcomes measurement can
      assist in comparing treatments and physicians, and in counseling patients on
      expected outcomes for localized prostate cancer interventions.

PMID- 16414490
TI  - Breast carcinoma metastasizing to the urinary bladder presenting as bilateral
      hydronephrosis treated with ureteral stenting and chemotherapy.
AB  - We describe a case of metastatic breast carcinoma involving the urinary bladder
      and causing bilateral hydronephrosis. Treatment consisted of bilateral renal
      decompression followed by chemoradiotherapy. The pertinent literature is
      reviewed.

PMID- 16414492
TI  - Puerperal renal rhabdomyosarcoma: case report and review of the literature.
AB  - Renal rhabdomyosarcoma is a rare malignant mesenchymal tumor with an aggressive
      clinical course. We describe the case of a 39-year-old woman with a large
      rhabdomyosarcoma of the left kidney serendipitously discovered
      ultrasonographically subsequent to cesarean section. To our knowledge, this is
      the first reported case of renal rhabdomyosarcoma during pregnancy. The
      importance of ultrasound examination in the differential diagnosis of gestational
      flank pain is discussed.

PMID- 16414491
TI  - Well-differentiated papillary mesothelioma occurring in the tunica vaginalis of
      the testis with contralateral atypical mesothelial hyperplasia.
AB  - Well-differentiated papillary mesothelioma (WDPM) occurs rarely in the
      paratesticular region, with only a handful of published case reports. Often
      presenting with recurrent hydrocele, WDPM is a multifocal mesothelial
      proliferation with a predominantly indolent clinical course. Accordingly,
      pathologic distinction of this lesion from true malignant mesothelioma is
      crucial, although it may be difficult because of the variability of associated
      histologic features. In addition, rare cases of WDPM have progressed to malignant
      mesothelioma, leading to its classification as a tumor of low malignant
      potential. Here, we report a case of multifocal WDPM occurring in the tunica
      vaginalis and tunica albuginea, with contralateral atypical mesothelial
      hyperplasia, a potentially premalignant lesion.

PMID- 16414493
TI  - Active surveillance for genitourinary cancer: an overview.

PMID- 16414494
TI  - Active surveillance with selective delayed intervention for favorable risk
      prostate cancer.
AB  - Good risk prostate cancer, defined as a Gleason score of < or = 6, prostate
      specific antigen (PSA) <10, and T1c-T2a, now constitutes 50% of newly diagnosed
      prostate cancer. Recent data from the Prostate Cancer Prevention Trial, Stamey
      data set on PSA-prostate cancer correlations, and the Surveillance, Epidemiology,
      and End Results database make it very clear that a policy of PSA screening with
      biopsy for those patients in whom PSA is increased results in the diagnosis, and
      radical treatment, of a very large proportion of men who do not have life
      threatening prostate cancer. Most men with good risk prostate cancer have
      indolent and slow growing disease. The challenge is to identify those patients
      who are unlikely to have significant progression, while offering radical therapy
      to those who are at risk. The approach to favorable risk prostate cancer
      described in this article uses estimation of PSA doubling time (DT) and repeat
      biopsy to stratify patients according to the risk of progression. Patients who
      select this approach are treated initially with active surveillance. Those
      patients who have a PSA DT of < or = 3 years (based on a minimum of 3
      determinations over 6 months) are offered radical intervention. The remaining
      patients are closely monitored with serial PSA and periodic prostate repeat
      biopsy at 1, 4, 7, and 10 years. In one series of 299 patients treated in this
      way, 65% remained free of treatment at 8 years. The prostate cancer specific
      survival using this approach was 99.3% at 8 years. The majority of patients in
      this study remain on surveillance. Active surveillance with selective delayed
      intervention based on PSA DT is a practical middle ground between radical therapy
      for all, which results in over-treatment of patients with indolent disease, and
      watchful waiting with palliative therapy only, which results in under-treatment
      of those with aggressive disease.

PMID- 16414495
TI  - Expectant treatment with curative intent in the prostate-specific antigen era:
      triggers for definitive therapy.
AB  - Expectant treatment with curative intent for treatment of low-risk prostate
      cancer faces 3 challenges in the PSA era: (1) appropriate patient selection, (2)
      adequate surveillance strategies, and (3) identification of triggers for
      definitive intervention when cure is still possible. Men 65 years or older with
      T1c disease, prostate-specific antigen density <0.15 ng/ml/cm3, and favorable
      biopsy characteristics per the Epstein criteria currently appear to be the safest
      candidates for expectant treatment. Changes in biopsy characteristics are the
      most objective trigger for definitive therapy currently in use. Outcomes data are
      still required to determine the safety of expectant treatment for localized
      disease.

PMID- 16414496
TI  - Expectant treatment of small, recurrent, low-grade, noninvasive tumors of the
      urinary bladder.
AB  - Low-grade, noninvasive tumors of the bladder pose little threat to the patient.
      The standard treatment is removal by transurethral resection or cautery when they
      are identified. Once a patient has a history of low-grade papillary tumors and a
      subsequent low-grade appearing tumor, there is no urgency to proceed with
      treatment. The growth rate of these tumors is slow and they rarely progress.

PMID- 16414497
TI  - Expectant management for the treatment of small renal masses.
AB  - The incidence of small renal masses that are detected incidentally is increasing,
      particularly in patients who are in advanced age and with increased
      comorbidities. We review the available data on the nature and natural history of
      these small renal tumors, and observe that based on the limited available
      information, most of these lesions appear to grow slowly. We also review the
      currently available markers of tumor progression. We postulate that because of
      tumor heterogeneity, it is unlikely that advancement in prognostic knowledge will
      be gained using current approaches, such as histologic characteristics and tumor
      size, and that there is a clear need for new biomarkers. We conclude that
      expectant management is a viable and safe option for the patient with a short
      life expectancy but potentially unsafe outside a well-controlled clinical trial
      in the younger and fit patient.

PMID- 16414498
TI  - Surveillance programs for stage I nonseminomatous germ cell tumors of the testis.
AB  - Germ cell tumors of the testes constitute approximately 1-2% of all tumors in
      males 15-35 years of age. Half of those present as clinical stage I disease. The
      traditional approach was either a retroperitoneal node dissection or
      radiotherapy. A historical review of the literature suggested that 70% of these
      patients were cured and did not benefit from further therapy. This coupled with
      the advent of tumor markers, advanced diagnostic techniques, and cisplatin based
      chemotherapy led to the consideration for surveillance programs, thereby offering
      therapy only to those who required it. This article reviews the surveillance
      programs described in the literature to date with respect to both suitability and
      program design.

PMID- 16414512
TI  - There are some debts in life that you can never repay: we remember Marshall M.
      Parks, MD.

PMID- 16414499
TI  - Surveillance in stage I testicular seminoma.
AB  - Treatment options in patients with stage I testicular seminoma include adjuvant
      radiotherapy (RT), surveillance, and adjuvant chemotherapy. RT was the treatment
      of choice for the past 50 years, but there has been increasing concern in the
      past decade regarding late complications. Surveillance, reserving treatment for
      patients who relapse, has been shown to be a safe and effective strategy. It
      allows >80% of patients to avoid any post-orchidectomy treatment and is the
      recommended approach for these patients. The possible role of adjuvant
      chemotherapy is currently being assessed in clinical trials and should not be
      used outside of a study setting.

PMID- 16414513
TI  - Marshall M. Parks, MD (1918-2005).

PMID- 16414514
TI  - Father to children's vision: Marshall M. Parks, MD.

PMID- 16414515
TI  - Can ophthalmologists repair the brain in infantile esotropia? Early surgery,
      stereopsis, monofixation syndrome, and the legacy of Marshall Parks.
AB  - Can ophthalmologists repair defects of visual cortex circuitry in infants who
      have esotropia? The answer to this question encompasses both sensory and motor
      behaviors because the clinical hallmarks of the disorder are stereoblindness and
      absence of motor fusion, which manifests as convergently deviated eyes.
      Functional recovery of sensory and motor fusion in infantile esotropia was a
      consuming interest, if not career-defining passion, of Marshall Parks. The
      purpose of this work is to pay tribute to Parks' legacy by showing how human and
      animal studies, conducted largely during the last 25 years, support both his
      clinical insights and treatment philosophy.

PMID- 16414516
TI  - Long-term study of accommodative esotropia.
AB  - PURPOSE: This study aimed, using a large sample size, to determine the long-term
      results of standard treatment of accommodative esotropia and identify predictors
      of outcome while minimizing bias in data collection and analysis. METHODS: Data
      from all the files of a large, long-established pediatric ophthalmology practice
      were collected and analyzed using a masked protocol. The study included every
      esotropic patient who had been prescribed glasses. Criteria for patient inclusion
      were designed to conform to earlier studies by the authors. RESULTS: The database
      totaled 1307 patients, of who 354 met inclusion criteria. A greater difference
      between near and distance esodeviation (AC/A relationship) correlated with a
      higher rate of deterioration of accommodative esotropia control (P < 0.0001).
      Deterioration also positively correlated with earlier age of onset (P < 0.0001),
      inferior oblique overaction (P = 0.0005), and amblyopia (P < 0.005). CONCLUSIONS:
      This study demonstrates that a high AC/A relationship increases the likelihood of
      deterioration of accommodative esotropia, supporting the earlier studies, as well
      as the accuracy of this database. It also represents a new model for the
      utilization of clinical trials' bias-reduction principals in the analysis of
      retrospective data.

PMID- 16414517
TI  - Visual acuity development after the implantation of unilateral intraocular lenses
      in infants and young children.
AB  - PURPOSE: Intraocular lenses (IOLs) are now being implanted in infants and
      children with unilateral cataracts. However, there are no prospective data on the
      development of visual acuity after implantation. The aim of the present study was
      to prospectively assess the development of acuity in infants and preschool
      children who received IOLs or aphakic contacts lenses (CLs) after the extraction
      of a unilateral cataract. METHODS: Visual acuity was assessed using Teller Acuity
      Cards and/or crowded HOTV tests at target ages of 6 months, 1, 2, 3, and 4 years.
      RESULTS: Infants who received a primary IOL after extraction of dense congenital
      unilateral cataract (n = 5) showed improvement from an initially low mean visual
      acuity of 20/170 at 6 months to 20/85 at 12 months and 20/54 at 4 years. Visual
      acuity in the IOL group was similar to that of children who had good-to-excellent
      compliance with CL wear (n = 36; 4-year visual acuity 20/50) and better than that
      of children who had moderate-to-poor compliance (n = 11; 4-year visual acuity
      20/135). Children who received IOLs after extraction of developmental unilateral
      cataracts by 6 months (n = 4; 4-year visual acuity 20/55) had visual acuity
      development similar to those treated with CLs (n = 5; 4-year visual acuity
      20/55). Children who received IOLs after extraction of developmental unilateral
      cataracts after 1 year of age (n = 18) had better visual acuity than children
      those treated with CLs (n = 4) at 4 years of age (20/40 vs. 20/135). CONCLUSION:
      IOLs and aphakic CLs support similar visual acuity development after surgery for
      a unilateral cataract. IOLs may support better visual acuity development when
      compliance with CL wear is moderate to poor or when a cataract is extracted after
      1 year of age.

PMID- 16414518
TI  - Characteristics and course of patients with deteriorated monofixation syndrome.
AB  - BACKGROUND: Monofixation syndrome is characterized by small-angle strabismus with
      vergence fusional amplitudes and "peripheral fusion." Although it is thought to
      be a relatively stable condition, some patients with this syndrome deteriorate,
      resulting in an increasing heterotropia, sometimes associated with diplopia.
      Deteriorated monofixation syndrome is well known among clinicians; however, there
      are no studies describing the course and outcomes for these patients. PURPOSE: To
      assess the clinical characteristics, course, and response to therapy of patients
      with deteriorated monofixation syndrome. METHODS: We identified all patients from
      our database that had an ocular deviation of < or =8 Delta on simultaneous prism
      cover testing, peripheral fusion, and between 3000 and 67 seconds of stereoacuity
      (monofixators) who subsequently had an increase in their deviation to >8 Delta,
      loss of fusion, or diplopia. From this group we assessed patient clinical
      characteristics, course, and response to therapy. RESULTS: We identified 29
      patients with deteriorated monofixation syndrome who subsequently underwent
      treatment. Treatment consisted of surgery in 28 patients and minus lens therapy
      in one patient. Of the study group, 28 (97%) of the patients had a history of
      esotropia and 20 patients (69%) had a history of amblyopia. Nine patients noted
      diplopia at the time of deterioration, which persisted in four patients after
      treatment. In all, 14 patients (48%) met the criteria for monofixation again
      after therapy, while 20 patients (69%) had successful motor alignment (< or =8
      Delta). There was a trend toward poorer outcomes in the diplopic group when
      compared with the patients who did not have diplopia, although this was not
      statistically significant (P = 0.26 for regaining monofixation syndrome). Follow
      up ranged from 1 month to 21 years. CONCLUSION: Though monofixation is considered
      a stable condition, some patients will deteriorate over time as demonstrated by
      an increase in the ocular deviation and loss of fusion. In this study 31% of our
      patients noted the onset of diplopia. Following treatment, 48% of the patients
      regained monofixation. Patients with diplopia following deterioration of their
      alignment may be less likely to regain good alignment or monofixation after
      treatment.

PMID- 16414519
TI  - Risk factors for amblyopia in congenital anterior lens opacities.
AB  - PURPOSE: We sought to identify the features of congenital anterior lens opacities
      (CALOs), which are associated with increased risk for amblyopia. METHODS: We
      undertook a retrospective study of 59 patients with CALO from 3 clinical
      practices. The following variables were examined: type (polar, subcapsular, or
      pyramidal), location (central, paracentral, or peripheral), diameter, presence of
      adherent iris tissue, anisometropia (spherical equivalent), unilateral versus
      bilateral, and presence or absence of amblyopia. Pearson chi-square and
      independent sample t-tests were conducted to evaluate if any of the
      aforementioned variables were independently associated with amblyopia. Relative
      risk was then calculated for significantly related variables (P < 0.05). RESULTS:
      Amblyopia was present in 17 of 59 patients (28.8%). Patients with amblyopia had a
      mean anisometropia of 1.23 diopters whereas nonambyopic patients had a mean
      anisometropia of 0.25 (P = 0.023). The relative risk for amblyopia with
      anisometropia of one diopter or greater was 6.5 (95% confidence interval = 3.79
      7.45). The mean cataract size in the amblyopic eyes was 1.22 mm (range, 0.7-2.0
      mm). Mean cataract size in the nonamblyopic eyes was 0.95 mm (range, 0.5-2.0 mm).
      This difference in mean cataract size was significant with independent sample t
      tests (P = 0.02); however, this difference did not remain significant with
      logistic regression. Cataract size was not a significant relative risk factor for
      amblyopia. CONCLUSIONS: Our overall incidence of amblyopia was 28.8%. The only
      variable associated with increased relative risk for amblyopia in this group of
      patients was anisometropia. Patients with CALO who have anisometropia of 1
      diopter or greater are 6.5 times more likely to develop amblyopia.

PMID- 16414521
TI  - Balloon dacryocystoplasty as the primary treatment in older children with
      congenital nasolacrimal duct obstruction.
AB  - PURPOSE: To report the outcomes of balloon dacryocystoplasty of the lacrimal duct
      with inferior turbinate infracture as a primary treatment of congenital
      nasolacrimal duct obstruction in children 18 months of age or older. MATERIALS
      AND METHODS: This study was a 3-year, prospective, interventional case series,
      consisting of 83 consecutive patients with congenital nasolacrimal duct
      obstruction who underwent balloon dacryocystoplasty as their primary treatment
      modality. Outcome evaluations included an ophthalmologic examination and a dye
      disappearance test at 3 weeks and 6 months postoperatively. We analyzed the
      different age groups and the types of obstruction noted at surgery to determine
      their respective influences on patient outcomes. We used the chi-square test for
      statistical analysis. RESULTS: Seventy-two patients aged 18 to 112 months (mean
      30 months) were included. Overall, 57 patients (79%) had good outcomes from
      balloon dacryocystoplasty. When analyzed by type of obstruction, 34/42 patients
      (81%) with simple membranous obstruction at the valve of Hasner had good outcomes
      and 23/30 patients (77%) with stenosis that extended along the length of the
      distal NLD had good outcomes (P = 0.60, power 0.62). Age did not significantly
      affect outcomes (P = 0.66, power 0.72). CONCLUSIONS: Balloon dacryocystoplasty is
      probably more effective than simple probing in older children with stenosis
      extending along the distal nasolacrimal duct obstruction.

PMID- 16414520
TI  - The effect of amblyopia therapy on ocular alignment.
AB  - PURPOSE: We sought to describe the change in ocular alignment at 2 years after
      treatment of amblyopia in children younger than 7 years of age at enrollment.
      METHODS: A randomized clinical trial of patching versus atropine for 6 months
      followed by standard clinical care for 18 months was conducted in 357 children
      with anisometropic, strabismic, or combined amblyopia (20/40-20/100) whose ages
      ranged from 3 to younger than 7 years at enrollment. Ocular alignment was
      evaluated at enrollment and after 2 years of follow-up. RESULTS: At enrollment
      when tested at distance fixation, 161 (45%) children were orthotropic, 91 (25%)
      had a microtropia (1-8 Delta), and 105 (29%) had a heterotropia >8 Delta. Of the
      161 patients with no strabismus, similar proportions of patients initially
      assigned to the patching and atropine groups developed new strabismus by 2 years
      (18% vs. 16%, P = 0.84). Of these cases of new strabismus, only 2 patients in the
      patching group and 3 patients in the atropine group developed a deviation that
      was greater than 8 Delta. Microtropia at enrollment progressed to a deviation
      greater than 8 Delta with similar frequency in both treatment groups (13% vs.
      15%, P = 1.00). Of the 105 patients with strabismus greater than 8 Delta at
      enrollment, 13% of those in the patching group and 16% of those in the atropine
      group improved to orthotropia without strabismus surgery. Strabismus surgery was
      performed in 32 patients during the 2-year study period. CONCLUSIONS: Patients
      who had amblyopia treatment with patching or atropine for 6 months followed by
      standard clinical care were found to have similar rates of deterioration and
      improvement of ocular alignment. When parents begin amblyopia treatment for
      children without strabismus, they should be warned of the possibility of
      development of strabismus, although it is most often a small angle deviation.
      Strabismus resolved after amblyopia therapy in some cases.

PMID- 16414522
TI  - Ocular overelevation in adduction in craniosynostosis: is it the result of
      excyclorotation of the extraocular muscles?
AB  - PURPOSE: We sought to determine whether radiological evidence supports
      excyclorotation of the extraocular muscle cone as a cause of overelevation in
      adduction in children with craniosynostosis. METHODS: This was a retrospective
      case series of 40 patients with craniosynostosis. Ophthalmic findings were
      assessed for incomitant vertical strabismus in particular excessive elevation in
      adduction. Computed tomography and magnetic resonance imaging scans were
      reviewed. Those scans with adequate coronal imaging of their orbits to assess the
      position and angulation of the horizontal extraocular muscles were identified,
      and the degree of rotation of the muscles formally measured along with aged
      matched controls. These groups were analyzed for the association between presence
      of overelevation in adduction and degree of excyclorotation of the extraocular
      muscle cone. RESULTS: The identified updrift on adduction that mimics inferior
      oblique muscle overaction was present in 63% (25/40) of patients. Imaging that
      permitted accurate measurement of the muscles positions was available in 10 of
      the 40 patients. Of these 10, 8 had the updrift, and 7 of these 8 (88%)
      demonstrated more excyclorotation than their aged matched controls. Comparison of
      scan measurements of patients revealed a significant difference in degree of
      excyclorotation (mean difference = 16.2, 95% confidence interval 6.2-31.5; P =
      0.006) between patients with and without excess elevation in adduction.
      CONCLUSION: Overelevation in adduction is significantly associated with
      excyclorotation of the extraocular muscle cone in children with craniosynostosis.
      We demonstrate a simple method to assess for the excyclorotation. Our findings
      support the importance of imaging of the orbits in these children before
      strabismus surgery.

PMID- 16414523
TI  - Silicone intubation with trans-sac fixation to prevent tube dislocation.
AB  - PURPOSE: To report a new technique for silicone tube fixation, after successful
      intubation for congenital nasolacrimal duct obstruction, to minimize its lateral
      dislocation. METHODS: Thirty patients (40 eyes) aged 20 months to 5 years
      (median, 28 months) were treated using the Ritleng bicanalicular lacrimal
      intubation system. After drawing the silicone stent out of the nose, a piece of 7
      O Prolene suture was tied securely around one of its limbs. This limb was then
      pulled up, pulling the tied end of the Prolene suture to the medial canthal area.
      The same procedure was repeated with the other limb of the stent, pulling up the
      other Prolene suture end. This suture end was then un-tied. After adjusting the
      exposed silicone loop, the free end of the Prolene suture was tied securely to
      the corresponding part of the silicon stent. The nasally drawn two ends of
      silicone tube were tied in a single square knot. After 2 to 3 months, stents were
      removed in the medical office for all the patients. RESULTS: This technique was
      used successfully for all the patients. Of the 40 tubes in this study, 39 did not
      displace and one tube was displaced laterally due to loosely tied Prolene suture.
      On follow-up, the trans-sac suture was well tolerated and no complications were
      noted. CONCLUSION: The trans-sac fixation suture prevents lateral displacement of
      square-knotted silicone tube, which still can be removed easily at the
      physician's office.

PMID- 16414524
TI  - Esotropia associated with early presbyopia caused by inappropriate muscle length
      adaptation.
AB  - BACKGROUND: The purpose of this study is to investigate the occurrence of
      esotropia accompanying early presbyopia. The two primary long-term mechanisms for
      maintenance of ocular alignment are vergence adaptation (neurologic) and muscle
      length adaptation (anatomic). Both mechanisms depend upon disparity-driven motor
      fusion for proper operation. A possible cause for an esotropic shift in early
      presbyopic adults with insufficient or absent disparity-driven motor fusion is
      inappropriate muscle length adaptation (medial rectus muscle shortening)
      occurring in response to increased convergence tonus accompanying increased
      accommodative effort. METHODS: Of 617 patients, age 10 and older who underwent
      surgery for esotropia during the period of 1980 to 1996, the age when the
      deviation occurred or worsened could be determined with confidence in 140. A plot
      was made of the number of these patients versus the age of onset of the
      deviation. This was compared with a similar plot of patients operated for
      exotropia. RESULTS: A statistically significant increase (P = 0.017) in the
      incidence of an esotropic shift in the age range from 30 to 50 years was found
      when compared with the incidence of an exotropic shift. CONCLUSION: If the
      postulated mechanism is correct, full correction of any hyperopia as well as
      prompt prescription of a reading add (or conversion to monovision correction) may
      help prevent further progression of small esodeviations accompanying early
      presbyopia.

PMID- 16414525
TI  - Conjunctival granulomas caused by synthetic fibers: report of two cases and
      review of literature.
AB  - PURPOSE: We sought to demonstrate the histopathologic and ultrastructural
      features of conjunctival foreign body granulomas because of synthetic fibers and
      to compare them to other cases published in the literature. METHODS: A 2- and a 7
      year-old girl were referred for the surgical removal of slow-growing unilateral
      inferior conjunctival masses with a lack of primary trauma or surgery. In this
      report, we describe the light and electron microscopic findings of the 2 cases
      and review the literature of similar cases using the Medline database. RESULTS:
      Histopathologic and ultrastructural examination of both specimens revealed a
      granulomatous inflammatory cell response, including histiocytes and
      multinucleated foreign body giant cells around acellular, uniform sized, oval to
      round birefringent fibers with manufacturing artifacts. Thirteen other patients
      with conjunctival synthetic fiber granulomas were identified from the literature.
      CONCLUSIONS: On the basis of the findings in our cases and the review of
      literature, it appears that conjunctival synthetic fiber granulomas are not a
      rare entity but are not recognized frequently by ophthalmologists. The most
      reliable clinical sign to suggest this diagnosis is the presence of a unilateral
      inferior conjunctival mass in a child or adolescent. Histopathologic and
      ultrastructural evaluation appears to be the only way to specifically diagnose
      this condition with certainty.

PMID- 16414526
TI  - An evaluation of the agreement between contour-based circles and random dot-based
      near stereoacuity tests.
AB  - INTRODUCTION: Monocular cues are present in the contour-based Titmus and Randot
      circles stereoacuity tests frequently giving rise to false-positive results in
      patients with abnormal stereoacuity. Stereoacuity derived using these 2 test
      types was compared to evaluate whether discrepancies between these tests were
      limited to the coarse/nil end of the stereoacuity spectrum or whether they were
      apparent across a wider range of possible stereoacuity scores, including levels
      of stereopsis equated with macular fusion. METHODS: Fifty-four normal volunteers
      and 91 patients with a history of anomalous binocular vision by a variety of
      conditions (eg, strabismus, monovision, or unilateral eye disease) participated.
      In each participant, stereoacuity was measured using the Titmus(c) circles, the
      Randot(c) (version 2) circles, and the Preschool Randot(c) Stereoacuity test.
      RESULTS: In patients with a history of anomalous binocular vision, better
      stereoacuity scores were acquired using the circles tests than the random dot
      based Preschool Randot Stereoacuity test (Friedman repeated-measures analysis of
      variance on ranks, Chi-square = 99.3, P < 0.001; Student-Newman-Keuls Method, P <
      0.05). Among patients with known binocular vision anomalies, stereoacuity score
      disagreement was evident across the entire range of measurable stereoacuity.
      CONCLUSIONS: Stereoacuity score discrepancies between the circles tests and the
      random dot based tests frequently cross categories (eg, fine vs. moderate or
      coarse stereopsis). Disagreement between the test types may reflect different
      underlying mechanisms by the different types of tests or confounding
      nonstereoscopic binocular cues in the Titmus and Randot circles test.

PMID- 16414527
TI  - Patterns of spectacle use in young Australian school children: findings from a
      population-based study.
AB  - PURPOSE: To describe the patterns of spectacle use in a population-based sample
      of Australian Year 1 school children (mostly aged 6 years). METHODS: Logarithm of
      the minimum angle of resolution (logMAR) visual acuity was measured in both eyes
      before and after pinhole correction, and using spectacles if worn. Cycloplegic
      autorefraction (cyclopentolate) and detailed dilated fundus examination were
      performed. Visual impairment was defined as visual acuity <40 logMAR letters (ie,
      <20/40 Snellen equivalent). Myopia was defined as spherical equivalent (SE)
      refraction < or = -0.50 diopters (D), and hyperopia as SE refraction > or =
      +2.0D, deemed significant when > or = +3.0D. Astigmatism was defined as cylinder
      > or =1.0D and anisometropia as SE refraction difference between the two eyes at
      least 1.0D. RESULTS: One thousand seven hundred forty predominantly 6-year-old
      school children were examined during 2003 to 2004. Spectacle use was documented
      in 77 children (4.4% of sample). Uncorrected visual impairment was found in the
      worse eye of 71 children (4.1%) and refractive error accounted for the majority
      (69.0%). Astigmatism was the most common refractive error causing visual
      impairment, accounting for 46.5%. Hyperopia, with or without astigmatism, was the
      most frequent reason for spectacle use, documented in 40.3%. Spectacle use in the
      absence of significant refractive error, amblyogenic risk factors, or visual
      impairment was noted in 26 children (33.8% of spectacle wearers). The
      prescription of spectacles could have benefited a further 26 children (1.5% of
      sample), mostly for correction of astigmatism. CONCLUSION: This study documents a
      significant disparity between spectacle use and need. Astigmatism was the most
      common cause of visual impairment due to refractive error.

PMID- 16414528
TI  - Retinopathy of prematurity: an optimum screening strategy.
AB  - OBJECTIVE: We sought to find out whether birth weight of less than 1251 g or
      gestational age less than 30 weeks could provide a safe and efficient screening
      criteria of detecting treatable retinopathy of prematurity (ROP). METHODS:
      Infants either with a birth weight less than 1500 g or gestational age less than
      32 weeks were screened for ROP during an 8-year period. RESULTS: In our study,
      the incidence of ROP was 36 of 187 (19.3%) infants. Although there was a slight
      increase in the number of infants screened over the years, the incidence of ROP
      of any stage remained stable. The maximum stage of ROP reached was stage 1 in 10
      of 187 (5.3%), stage 2 in 8 of 187 (4.3%), and stage 3 in 18 of 187 (9.6%)
      infants. Among those with stage 3 disease, threshold ROP was present in 16 of 18
      (88.9%). All infants with threshold ROP had a BW less than 1100 g and gestational
      age less than or equal to 28 weeks. Significantly fewer babies (105/187, or 56%)
      would have been examined had inclusion criteria of a birth weight of less than
      1251 g and gestational age less than 30 weeks been applied. In addition, 31%
      (134/437) of screening examinations could have been avoided. CONCLUSIONS: Our
      study suggests that a birth weight of less than 1251 g and gestational age less
      than 30 weeks can be safely and efficiently used to screen infants without
      missing a diagnosis of sight-threatening ROP in our catchment population.

PMID- 16414529
TI  - Loop myopexy for treatment of myopic strabismus fixus.
AB  - In myopic strabismus fixus, there is acquired esotropia and hypotropia associated
      with restricted elevation and abduction. One possible etiology is an enlarged
      globe herniating superotemporally through the muscle cone. High-resolution
      magnetic resonance imaging (MRI) has demonstrated the inferolateral displacement
      of the lateral rectus (LR) muscle in this restrictive motility disorder. Surgical
      treatment is difficult. We report two cases of myopic strabismus fixus that were
      treated with a loop myopexy of the LR and superior rectus (SR) muscles.

PMID- 16414530
TI  - Endoscopic closure of a cyclodialysis cleft.
AB  - Numerous surgical procedures have been proposed to close cyclodialysis clefts. We
      describe a novel technique, direct cyclopexy under microendoscopic view, in a
      patient with persistent hypotony despite previous attempts at both surgical
      repair and cryotherapy for her cyclodialysis cleft.

PMID- 16414531
TI  - Localized, extreme scleral thinning causing globe rupture during strabismus
      surgery.
AB  - Eye muscle surgery in strabismus patients usually is without serious, vision
      threatening complications. The risk of scleral perforation during strabismus
      surgery has been reported to approximately 1% but usually without serious
      sequelae. Inadvertent perforation may occur during muscle disinsertion or during
      muscle reattachment. The risk of perforation is increased in myopic eyes, and the
      risk is higher in recessions than in other strabismus procedures. We report a
      case of sudden rupture of the globe during a recession procedure on the superior
      rectus muscle caused by a localized area of extreme scleral thinning adjacent to
      the muscle insertion. To our knowledge, this serious complication has not
      previously been reported.

PMID- 16414532
TI  - Herpes zoster ophthalmicus in an otherwise-healthy child.
AB  - Herpes zoster ophthalmicus, although not uncommon in adults, is rarely found in
      children. Herein we present a case of pediatric herpes zoster ophthalmicus that
      is unique in 2 ways. First, the child had been vaccinated against varicella and
      otherwise had no known exposure to varicella-zoster virus. Second, the initial
      presentation of herpes zoster ophthalmicus was a painful and diffuse
      subconjunctival hemorrhage that appeared before any of its classic signs were
      observed. We report this case to document the possible occurrence of herpes
      zoster ophthalmicus in children who have been vaccinated against varicella and
      the possibility of a diffuse, painful subconjunctival hemorrhage as a presenting
      sign.

PMID- 16414533
TI  - Bilateral acute retinal necrosis in a 12-year-old girl.
AB  - Acute retinal necrosis (ARN) is a severe ocular syndrome consisting of a moderate
      to-severe anterior uveitis, vasculitis, and vaso-occlusive retinal necrosis. It
      can occur in healthy individuals at any age, but reports of this condition in
      children are rare.

PMID- 16414534
TI  - Orbital cellulitis after strabismus surgery.
AB  - Serious infection is uncommon after eye muscle surgery. Orbital cellulitis is a
      rarely reported but is potentially vision- and life-threatening complication
      after strabismus surgery. In this report, we describe a case of unilateral
      orbital cellulitis after strabismus surgery for sensory exotropia in a healthy
      adolescent boy.

PMID- 16414535
TI  - The phenotypic spectrum of baraitser-winter syndrome: a new case and review of
      literature.
AB  - The syndrome of iris coloboma, ptosis, hypertelorism, and mental retardation
      (Online Mendelian Inheritance in Man -- OMIM # 243310), also known as the
      Baraitser-Winter syndrome, originally was described in a brother and sister and
      in an unrelated girl in 1988. Six additional individuals with a similar phenotype
      have been reported in the world literature. Microphthalmos, microcornea, and
      brain malformations were added to the phenotypic spectrum of this syndrome in
      1995. We report a child who presented with the aforementioned findings. Eye
      examination revealed bilateral microphthalmos and typical iris, optic nerve, and
      choroidal colobomas. Magnetic resonance imaging of the brain demonstrated
      pachygyria and cortical atrophy.

PMID- 16414537
TI  - The sclerosing variant of adenoid cystic carcinoma: a previously unrecognized
      neoplasm of major salivary glands.
AB  - We report 2 cases of a previously unrecognized sclerosing variant of adenoid
      cystic carcinoma (ACC) of major salivary glands. One of the tumors arose in the
      parotid and the other in the submaxillary gland of young adult patients. The
      tumors were composed predominantly of varying-sized large sclerotic and
      hypocellular nodules containing myoepithelial cells and pseudovascular spaces,
      most likely the result of artifactual retraction. In moderately cellular nodules,
      there were numerous small globules or spherules surrounded by myoepithelial cells
      similar to those of collagenous or mucinous spherulosis. Focal cribriform areas
      and ductal structures lined by epithelial cells were also identified. Both tumors
      showed perineural invasion. Electron microscopy revealed that both large nodules
      and small globules or spherules were composed of excessive amounts of basement
      membrane and thick-banded collagen fibers. The myoepithelial cells showed
      immunoreactivity for smooth muscle actin (SMA), S100 protein, and vimentin.
      Collagen IV showed variable reactivity in both the large nodules and small
      spherules. More cases of the sclerosing variant of ACC and long-term follow-up of
      the patients are needed to determine the biologic behavior of this unusual but
      distinctive variant of ACC.

PMID- 16414539
TI  - Vascular tumors in the orbit--capillary and cavernous hemangiomas.
AB  - Vascular tumors in the orbit result from new formation of vessels, proliferation
      of tissue components of the vessel wall, and hyperplasia of cellular elements
      ordinarily concerned with the genesis of vascular tissue. These vasculogenic
      lesions constitute the largest group of primary orbital tumors; we present the
      capillary hemangioma and the cavernous hemangioma.

PMID- 16414540
TI  - Intradiploic primary epithelial inclusion cyst of the skull.
AB  - Intradiploic inclusion cyst of the skull presenting as a calvarial defect is
      fairly uncommon in the neuroscience practice. They are benign in nature, slow to
      grow, and clinically difficult to differentiate from other causes of calvarial
      defects. We present a case of a healthy 55-year-old woman who presented
      clinically for an asymptomatic lump over the right parieto-occipital region of
      the scalp of 4-month duration. The radiological features were suggestive of
      presence of a large intradiploic solitary cyst and additional multiple lytic
      defects with sclerotic borders, destroying the underlying bone. The gross and
      histomorphological features of the right parieto-occipital craniectomy specimen
      received were pathognomic of an intradiploic primary epithelial inclusion cyst of
      the skull bone. The importance of its benign nature, embryogenic origin, and
      differentiation from other cystic lesions with similar histology is stressed. We
      report this case for its unique histomorphology and first of its kind in the
      Indian literature.

PMID- 16414538
TI  - Plasmablastic lymphoma: a clinicopathologic correlation.
AB  - Plasmablastic lymphoma (PBL) is an uncommon, recently described B-cell-derived
      lymphoma that displays distinctive affinity for extranodal presentation in the
      oral cavity. Plasmablastic lymphoma is strongly associated with human
      immunodeficiency virus (HIV) infection, but has been reported in HIV-negative
      individuals. Plasmablastic lymphoma may be poorly recognized by pathologists,
      which is partly attributable to its relatively rare occurrence and unusual
      immunophenotype. Five cases of oral cavity lymphomas conforming to the current
      World Health Organization morphological criteria for PBL were retrieved from the
      consultation files at the Armed Forces Institute of Pathology. An
      immunohistochemical panel consisting of CD3, CD20, CD30, CD38, CD45RB, CD79a,
      CD138, Bcl-2, Bcl-6, Alk-1, Ki-67, EBV-LMP-1, and HHV8 was performed. All 5 cases
      were immunoreactive for CD38 and/or CD138, confirming plasma cell differentiation
      of the tumor cells. CD20 was immunoreactive in 1 case, and CD79a was positive in
      2 cases. HHV8 and EBV-LMP-1 were nonreactive in all cases. Follow-up revealed
      only 1 patient alive with no evidence of disease. Our cases show that PBL is an
      aggressive type of B-cell lymphoma predominantly found in the oral cavity.
      Plasmablastic lymphoma is often associated with HIV infection.

PMID- 16414541
TI  - Bone manifestations of actinomycosis.
AB  - Actinomycosis, originally classified as a fungus, is now considered a branching
      bacteria. Although jaw involvement often presents with classic pathognomonic
      signs, postcranial disease has not been so characterized. Affected bones from
      individuals diagnosed in life with actinomycosis were macroscopically and
      radiologically examined for their macroscopic character. The bones were riddled
      with spheroid, occasionally coalescing defects associated with periosteal
      reaction. Erosion penetrated cortical bone as readily as through cortical bone or
      subchondral bone. X-ray revealed circular lesions with a slight sclerotic margin.
      Actinomycosis apparently has unique features, which should allow it to be
      distinguished from multiple myeloma (because of presence of reactive new bone
      formation) and from fungal disease (because of lack of "fronts of resorption" and
      penetrating spicules). Similarity to fungal infection is especially of interest
      because of the earlier phylogenetic classification question.

PMID- 16414542
TI  - Primary hepatic neuroendocrine carcinoma: an underdiagnosed entity.
AB  - Primary hepatic neuroendocrine tumors are rare. We report a case of a primary
      neuroendocrine carcinoma of the liver with a review of the literature. In earlier
      reports, all of these tumors were named hepatic carcinoids. We now recognize that
      they belong to a heterogeneous group of neoplasms, with microscopic appearance
      not necessarily predictive of biologic behavior. To our knowledge, only 55 cases
      have been reported in the English literature. This entity has probably been
      underreported because of the assumption that it represents a metastatic lesion. A
      search for an occult primary neuroendocrine tumor outside the liver must always
      be pursued.

PMID- 16414543
TI  - True thymic hyperplasia associated with a unilocular thymic cyst: an unusual
      combination not previously reported.
AB  - A mediastinal tumor mass in a 53-year-old woman with the sole complaint of
      persistent cough was studied and found to be a true thymic hyperplasia associated
      with a unilocular thymic cyst, felt to be of the congenital type. The bilobed
      thymus obtained was macroscopically and microscopically normal except for the
      size (12 x 12 x 3.5 cm) and weight (97 g). It showed normal thymic tissue
      segregated in lobules separated by adipose septa and with good corticomedullary
      separation. There were numerous Hassall corpuscles in the medullary portion. The
      thymus-to-adipose ratio was approximately 80:20. In the anterior aspect of the
      thymus, there was a 5-cm unilocular cyst, filled with a clear watery fluid, and
      with smooth and gray white inner surfaces. Microscopically, the cyst was lined by
      a cubic and low cylindrical nonciliated epithelium with normal-appearing thymic
      tissue in the cyst wall. This very unusual combination of true thymic hyperplasia
      and unilocular thymic cyst has not been previously reported in the literature.

PMID- 16414544
TI  - Detection of TLS/FUS-CHOP fusion transcripts in a case of oral liposarcoma.
AB  - OBJECTIVE: The aim of this study was to detect the chromosomal translocation
      t(12;16)(q13;p11) that leads to a gene fusion encoding a FUS-CHOP chimeric
      protein and has been shown to be highly characteristic of myxoid and round cell
      subtypes of liposarcoma, in a case of oral myxoid liposarcoma. METHOD AND
      MATERIALS: Nested reverse transcriptase-polymerase chain reaction to detect the
      TLS/FUS-CHOP fusion gene transcript was performed. A case of inflammatory fibrous
      hyperplasia and a case of oral lipoma were included as negative controls.
      RESULTS: Only the myxoid oral liposarcoma showed a 103-base pair product,
      specific of TLS/FUS-CHOP fusion type II transcript. CONCLUSION: The
      identification of FUS-CHOP transcript is potentially useful in the diagnosis and
      research of oral liposarcomas.

PMID- 16414545
TI  - Advances in the pathologic diagnosis and biology of acute myeloid leukemia.
AB  - In a general surgical pathology practice, cases of acute myeloid leukemia (AML),
      including myeloid sarcoma, are relatively rare; the diagnosis is very often
      difficult, however, and consequences of a missed or improper diagnosis compromise
      patient care. Currently, accurate diagnosis of every case of AML requires
      integration of the morphological features and results of cytochemical and
      immunohistochemical stains, flow cytometric immunophenotyping, cytogenetics, and
      molecular studies. This review focuses on a practical approach to diagnosis of
      AML according to current standard of practice and discusses some of recent
      changes in the field of AML.

PMID- 16414547
TI  - Peripheral neuropathy in a woman with breast cancer.

PMID- 16414548
TI  - Pain and attention: attentional disruption or distraction?
AB  - The effect of pain processing on attention capacity during visual search was
      examined in 2 experiments. In the first experiment, we investigated whether pain
      draws on the same limited resources as attentional task performance. It was
      hypothesized that pain would negatively affect task performance under different
      load manipulations. Low and high load conditions of a visual search task were
      presented in a mixed design combined with a painfully cold or neutral cold
      pressor test. Performance was not affected by pain. In experiment 2, low and high
      load conditions were separated in different blocks to study whether pain
      perception was affected when task load could be anticipated. Again, pain did not
      significantly affect task performance. In contrast, subjective pain intensity
      scores were significantly lower after performing the high load compared with the
      low load condition. Simultaneous recordings of event-related potentials indicated
      an increased negativity during the pain compared with the control condition.
      Also, in the early (350 to 450 msec) interval of event-related potentials, an
      increase in negativity was found for the high load compared with the low load
      condition. Topographic distributions suggested that pain and task load are
      mediated by qualitatively different resources. PERSPECTIVE: Our findings indicate
      that highly demanding attentional task performance and pain processing interfere
      as a result of difficulties in allocating attention. The clinical relevance of
      this finding is that performing a highly demanding task might distract attention
      from pain.

PMID- 16414549
TI  - The interruptive effect of pain on attention.

PMID- 16414550
TI  - Pain catastrophizing, but not injury/illness sensitivity or anxiety sensitivity,
      enhances attentional interference by pain.
AB  - Pain draws on attentional resources, thereby disturbing the pursuit of ongoing
      activities. Several studies have made use of the primary task paradigm to study
      the disruptive function of pain on attention. In this paradigm, participants
      perform an attentionally demanding task, while they are occasionally distracted
      by mild electrical stimulation. Deterioration in task performance (in terms of
      speed and accuracy) is then taken as an index of attentional interference. One
      major finding with this paradigm was that pain catastrophizing enhances
      attentional interference. The current study aimed to replicate this finding and
      to explore the possible influence of anxiety sensitivity and injury/illness
      sensitivity on attentional interference. Healthy volunteers (n = 48) performed an
      auditory discrimination task and were thereby occasionally distracted by low
      electrocutaneous stimulations. The performance on the discrimination task was
      subsequently related to participants' scores on the Pain Catastrophizing Scale,
      the Anxiety Sensitivity Index, and the Injury/illness Sensitivity Index. We were
      unable to demonstrate an association of either injury/illness sensitivity or
      anxiety sensitivity with attentional interference. Results did, however, confirm
      the finding that pain catastrophizing enhances attentional interference.
      PERSPECTIVE: The present study showed that pain disrupts ongoing activities. This
      effect is enlarged in those with high levels of pain catastrophizing and is
      related to the threatening nature of pain stimuli. The role of anxiety
      sensitivity and injury/illness sensitivity seems to differ from the role of
      catastrophizing and needs further research.

PMID- 16414551
TI  - Pain and attention: a discussion of two studies.

PMID- 16414552
TI  - Calibrated forceps: a sensitive and reliable tool for pain and analgesia studies.
AB  - Devices designed for mechanical pain threshold studies are often difficult to
      implement. The purpose of this study was to investigate a simple tool based on
      calibrated forceps to induce quantifiable mechanical stimulation in the rat on a
      linear scale. The most suitable protocol was tested by determining the effects of
      3 repetitive measurements on both hind paws, respectively, during long-term (9
      days), mid-term (1 day), and short-term (2 hours). Only threshold increase
      related to weight gain over long-term was observed, suggesting that moderate rat
      training can be used. The capacity of the device to reveal hyperalgesia was
      tested in a model of carrageenan-induced inflammation in the hind paw. The
      hyperalgesia was maximal 6 hours after carrageenan injection and progressively
      decreased. Similar, although more variable, responses were observed with von Frey
      filaments. Morphine-induced analgesia resulted in a dose-dependent increase of
      paw threshold. Tolerance to morphine administrated on a once daily schedule (10
      mg/kg) during 5 days was revealed by a significant decrease in analgesia by day
      3. Taken together, these results demonstrated accuracy of this device for easy,
      fast, and reproducible measure of mechanical pain threshold on rat limbs.
      Moreover, it allows the performance of rat testing with minimal constraint, which
      reduces data variability. PERSPECTIVE: The calibrated forceps is an easy to use
      device well-suited to rapidly test mechanical pain threshold with accuracy. It is
      well-designed for preclinical behavioral screening of noxious or analgesic
      properties of molecules.

PMID- 16414553
TI  - Calibrated forceps: a useful tool to study mechanical nociception.

PMID- 16414554
TI  - Opioid tolerance and hyperalgesia in chronic pain patients after one month of
      oral morphine therapy: a preliminary prospective study.
AB  - There is accumulating evidence that opioid therapy might not only be associated
      with the development of tolerance but also with an increased sensitivity to pain,
      a condition referred to as opioid-induced hyperalgesia (OIH). However, there are
      no prospective studies documenting the development of opioid tolerance or OIH in
      patients with chronic pain. This preliminary study in 6 patients with chronic low
      back pain prospectively evaluated the development of tolerance and OIH. Patients
      were assessed before and 1 month after initiating oral morphine therapy. The cold
      pressor test and experimental heat pain were used to measure pain sensitivity
      before and during a target-controlled infusion with the short-acting mu opioid
      agonist remifentanil. In the cold pressor test, all patients became hyperalgesic
      as well as tolerant after 1 month of oral morphine therapy. In a model of heat
      pain, patients exhibited no hyperalgesia, although tolerance could not be
      evaluated. These results provide the first prospective evidence for the
      development of analgesic tolerance and OIH by using experimental pain in patients
      with chronic back pain. This study also validated methodology for prospectively
      studying these phenomena in larger populations of pain patients. PERSPECTIVE:
      Experimental evidence suggests that opioid tolerance and opioid-induced
      hyperalgesia might limit the clinical utility of opioids in controlling chronic
      pain. This study validates a pharmacologic approach to study these phenomena
      prospectively in chronic pain patients and suggests that both conditions do occur
      within 1 month of initiating opioid therapy.

PMID- 16414555
TI  - Asking the community about cutpoints used to describe mild, moderate, and severe
      pain.
AB  - Clinical practice guidelines recommend that numeric rating scales be used to
      document the severity of perceived pain, yet patients and clinicians often opt to
      use simpler classification systems such as mild, moderate, or severe. To assess
      how well the numeric scales correlate with the tri-level classification system
      for describing pain severity, we conducted a subanalysis of a larger population
      based study of pain management preferences. Our primary objective was to identify
      the numeric boundaries used by 287 adults to describe pain as mild, moderate, or
      severe. We examined differences in the means of the upper and lower limits for
      mild, moderate, and severe pain according to demographic characteristics and type
      of pain. Ranges reported for each pain level were 1.3 to 3.6 (mild), 4.3 to 6.5
      (moderate), and 7.5 to 9.8 (severe). The primary finding was that "healthy"
      community adults rated the pain severity cutpoints much as patients with clinical
      pain did, 1 to 4 for mild, 5 to 6 for moderate, and 7 to 10 for severe. These
      results suggest that numeric rating scales can be used in clinical practice with
      both patients and community-dwelling adults. Our findings also support
      encouraging the general public to use a 0 to 10 scale to rate their pain
      intensity. PERSPECTIVE: Methods used to describe numeric cutpoints for mild,
      moderate, and severe pain were applied to community adults. Having standard
      categories to describe pain severity might increase clinicians' confidence in
      using a numeric scale to make treatment decisions. Further studies of cutpoint
      methodology and its clinical importance are warranted.

PMID- 16414556
TI  - Time course and dose-dependence of nerve growth factor-induced secondary
      hyperalgesia in the mouse.
AB  - Administration of the neurotrophin nerve growth factor (NGF) to rats and humans
      has been shown to induce both thermal and mechanical hyperalgesia and is used as
      a model of inflammatory pain. Here we describe a mouse model of secondary
      hyperalgesia after NGF application. NGF was injected into the biceps femoris
      muscle unilaterally, and at various intervals afterwards the electromyographic
      (EMG) activity from the same muscle was recorded in response to mechanical von
      Frey hair stimulation of the plantar surface of the hind paw in isoflurane
      anesthetized mice. Secondary cutaneous hyperalgesia in the hind paw reached a
      peak 60 minutes after injection and returned to baseline levels after an
      additional 60 minutes. This was followed by a second increase in EMG magnitude at
      24 hours after injection that was still present after 5 days. The effects of NGF
      were dose-dependent, and a dose of 2 microg/g NGF had the maximal observed
      effect. No increase in EMG magnitude occurred on the untreated side. This study
      describes a quantitative mouse model of prolonged secondary cutaneous
      hyperalgesia after NGF-induced muscle inflammation that can be used for genetic
      manipulations of putative central molecular pathways that underlie secondary
      hyperalgesia. PERSPECTIVE: This study describes the development of a novel model
      of NGF-induced secondary hyperalgesia. The development of this model will allow
      further investigations into the processes that underlie the development of
      secondary hyperalgesia and pain associated with the musculature.

PMID- 16414557
TI  - Effects of focusing and distraction on cold pressor-induced pain in chronic back
      pain patients and control subjects.
AB  - Previous studies showed equivocal findings regarding the efficacy of focused
      attention and distraction to experimental pain. This study examined the relative
      efficacy of these strategies on perception of cold pressor pain in 41 chronic
      back pain patients and 41 healthy control participants. Participants were
      randomized to the 2 strategies and then completed a 7-minute cold pressor test.
      Pain intensity and discomfort ratings were obtained during the task. Participants
      who completed the first task were asked to complete a second cold pressor task
      without instructions. Pain and discomfort ratings differed by condition across
      time. In the distraction condition, pain levels started low but continued to rise
      throughout the cold pressor immersion, whereas in the focused attention
      condition, pain levels started higher, rose less quickly, and then decreased from
      the middle of the task. Focused attention was associated with higher pain and
      lower completion rates in chronic pain patients compared with healthy control
      subjects. Focused attention might therefore not be an effective intervention
      strategy for individuals with chronic back pain. Finally, in the second cold
      pressor test, patients' pain reports rose more rapidly than those of healthy
      control subjects. The results of this study can be explained in terms of
      differences in cognitive appraisal between pain patients and healthy control
      participants. PERSPECTIVE: Marked differences were found between chronic back
      pain patients and control participants regarding focused attention as compared
      with distraction as a means of coping with cold pressor-induced pain. These
      differences underline the importance of taking into account previous experience
      with pain when recommending strategies to cope with painful procedures.

PMID- 16414559
TI  - Primary care for twins and higher order multiples.

PMID- 16414561
TI  - Antibacterial screening of Citrullus colocynthis.
AB  - Crude ethanolic extracts of fruits, leaves, stems and roots of Citrullus
      colocynthis Schrad were examined for their antibacterial potentialities against
      Gram positive and Gram negative bacilli. Ethanolic extracts of fruits, leaves,
      stems and roots were found to be active against Gram positive bacilli, viz.,
      Bacillus pumilus and Staphylococcus aureus, while fruit and root extracts in
      double strength gave positive results against Gram positive bacillus (Bacillus
      subtilis). The Gram negative bacilli viz., Escherichia coli and Pseudomonas
      aeruginosa showed no response.

PMID- 16414562
TI  - Antidiarrheal activity of the methanol extract of Ludwigia hyssopifolia Linn.
AB  - Dried whole plant parts of Ludwigia hyssopifolia were subjected to successive
      cold extraction with n-hexane, ethylacetate and methanol. The methanol extract
      (LHM), obtained as 1% yield, showed significant antidiarrheal property by
      reducing diarrheal episodes in castor oil and serotonin induced diarrhea in
      laboratory mice at a dose of higher than 100 mg/kg body weight as compared to
      standard drug loperamide given at a dose of 66.67 microg/kg body weight. The
      percent reduction in diarrheal episode by 56.32 and 89.66 after castor oil
      challenge and 59.09 and 86.36 in serotonin induced diarrhea was observed at doses
      of 200 mg/kg and 400 mg/kg body weight of the extract respectively. The extract
      LHM was also found to reduce the gastrointestinal motility by 53.8% at a dose of
      100 mg/kg body weight as compared to control, while no remarkable inhibition of
      gastrointestinal motility was seen at a dose of 50 mg/kg body weight of the
      extract.

PMID- 16414563
TI  - Effect of co administration of haloperidol and large neutral amino acids
      (tryptophan and valine) on rats striatal dopamine, serotonin and their
      metabolism.
AB  - Haloperidol is a high potency typical neuroleptic used in the treatment of
      schizophrenia. Administration of haloperidol produces muscles related side
      effects commonly known as extrapyramidal effects (EPS). These effects are not
      produced following the administration of atypical neuroleptics such as clozapine.
      A severe side effect of clozapine treatment is however, agranulocytosis.
      Development of antipsychotics with little/no EPS and/or other side effects is one
      of the exploring fields of drug research. This involves investigation on the
      mechanism by which a typical neuroleptic acting via serotonergic mechanism tends
      to produce less or no EPS. The present study is, therefore, designed to determine
      the effect of serotonin precursor tryptophan and a large neutral amino acid
      (valine) other than tryptophan on the modulation of neurochemical changes in the
      striatum. Neurochemical estimation were done by HPLC-EC. Present study showed
      that administration of tryptophan increased tryptophan, 5HT, 5HIAA and DA
      concentration in the striatum. DOPAC and HVA were not effected. Administration of
      valine increased DOPAC concentration in the striatum and did not alter
      tryptophan, 5HT, 5HIAA, DA and HVA concentration. Administration of the
      haloperidol increased HVA, 5HT and 5HIAA concentration. No effect was produced on
      tryptophan, DOPAC and DA levels. Valine administration followed by haloperidol
      injection did not alter striatal tryptophan, 5HT, DA, DOPAC and HVA concentration
      but decreased 5HIAA concentration. Administration of tryptophan followed by
      haloperidol injection increased tryptophan and 5HT concentrations and decreased
      DA levels. No effect was produced on 5HIAA, DOPAC and HVA concentrations.
      Administration of TRP increased plasma and brain concentration as well as DA
      levels in the striatum. Administration of valine did not decrease striatal TRP
      concentration while Haloperidol increased striatal 5-HT and 5-HIAA concentrations
      and no change in DA levels after haloperidol administration. whereas prior
      injection of TRP that increased 5HT concentration did not alter haloperidol
      induced DA turnover in the brain.

PMID- 16414564
TI  - Effects of 2 hrs. restraint stress on brain serotonin metabolism and memory in
      rats.
AB  - Stress is a non-specific response of body to any physiological and psychological
      demand. Studies on experimental animals show that uncontrollable stress situation
      produce neurochemical and behavioral deficits In the present study effects of 2
      hrs. restraint stress were monitored on brain serotonin metabolism and memory in
      starved rats. An episode of 2 hrs. restraint stress exhibited a significant
      decrease in food intake as well as in growth rate in starved rats. The memory
      function was significantly enhanced following 2 hrs. restraint stress in starved
      rats. The concentration of Noradrenaline (NA) and Dihydroxyphenyl acetic acid
      (DOPAC) were increased in the brain while no effect of restraint stress was
      observed on brain Dopamine (DA) level. Brain levels of 5-hydroxy indoleacetic
      acid (5-HIAA) was significantly decreased in restraint rats. Tryptophan levels in
      brain as well as in plasma significantly decreased in starved rats following 2
      hrs. restraint stress. The findings are explained in terms of enhanced memory
      function following restrained stress which may be associated with a decrease in
      serotonergic function in starved rats.

PMID- 16414565
TI  - In vitro availability of gliclazide in presence of antacids.
AB  - Gliclazide is the most commonly used sulfonylurea derivative for NIDDM therapy.
      Due to its prolonged therapy, there is always a likelihood of its use with other
      drugs. On the other hand antacids are commonly prescribed to encounter gastric
      acidity etc. Present paper deals with the in vitro availability studies of
      gliclazide in presence of antacids. These studies were carried out in simulated
      gastric juice and in buffer of pH 7.4 at body and accelerated temperature. The
      antacids used in these studies were aluminum hydroxide, aluminum trisilicate,
      magnesium oxide, magnesium trisilicate, sodium bicarbonate, calcium carbonate,
      magaldrate and simethicone (2,4-dimethoxypoly-siloxane). It has been found that
      in case of magnesium oxide, magnesium trisilicate and sodium bicarbonate,
      availability of gliclazide was enhanced while in rest of the antacids retarded
      the availability of gliclazide.

PMID- 16414566
TI  - Injected tryptophan increases brain but not plasma tryptophan levels more in
      restrained rats.
AB  - Immobilization stress given for one hour decreased cumulative food intake and
      growth rate in rats. Activity in an open field scored next day was also smaller
      in the restrained animals. Stress is known to enhance brain serotonin (5
      hydroxytryptamine; 5-HT) metabolism. It is however not clear, whether this
      enhancement is caused by an increase in the activity of tryptophan hydroxylase,
      the rate limiting enzyme of 5-HT biosynthesis or availability of the precursor
      tryptophan to the brain. In order to determine the utilization of tryptophan via
      serotonin path way in brain during stress; rats were injected with saline or
      tryptophan (50 mg/kg, i.p.). A group of both saline and tryptophan injected
      animals was restrained for one hour, while another group left unrestrained. The
      animals were killed immediately after the termination of stress period to collect
      plasma and brain samples. Injected tryptophan resulted in 3-4 fold rise of plasma
      tryptophan in both unstressed and stressed animals in one hour. Stress alone
      however had no effect on plasma total tryptophan concentration. Free tryptophan
      in plasma, brain tryptophan, 5-HT and 5-hydroxyindole acetic acid (5-HIAA) all
      increased by both stress and tryptophan injection. The increases of brain
      tryptophan, 5-HT and 5-HIAA but not of free tryptophan in plasma were
      considerably greater in restrained animals given tryptophan load. The results
      suggest that enhancement of brain serotonin metabolism during stress is caused by
      an increase in the availability of tryptophan to the brain as well as an increase
      in the activity of the enzyme tryptophan hydroxylase. Factors affecting the
      availability of tryptophan to the brain are discussed.

PMID- 16414567
TI  - Synthesis and antibacterial activity of cephradine metal complexes: part I
      complexes with magnesium, calcium, chromium and manganese.
AB  - Cephradine is included among the first generation cephalosporins, which is active
      against a wide range of Gram-positive and Gram-negative bacteria including
      penicillinase-producing Staphylococci. Since the presence of complexing ligand
      may affect the bioavailability of a metal in the blood or tissues, therefore, in
      order to study the probable interaction of cephradine with essential and trace
      elements present in human body, cephradine has been reacted with cobalt, copper,
      zinc and cadmium metal halides in L:M ratio of 2:1 in methanol and the products
      recrystallized from suitable solvents to pure crystals of consistent melting
      points. Infrared and ultraviolet studies of these complexes were carried out and
      compared with ligand. Magnetic susceptibility studies of these complexes were
      also carried out showing their paramagnetic behavior. From the infra red studies
      and elemental analysis of the complexes it has been shown that the drug molecule
      serves as a bidentate ligand coordinating through both its carboxylate at C-3 and
      beta -lactam nitrogen and the metal having a square planar or octahedral
      geometry. To evaluate the changes in microbiological activity of cephradine after
      complexation, antibacterial studies were carried out by observing the changes in
      MIC (minimum inhibitory concentration) of the complexes and compared with the
      parent drug by measuring the zone of inhibition of complexes against both Gram
      positive and Gram-negative organisms. For MIC observation, serial dilution method
      was employed and zone series were determined by disk diffusion method. Our
      investigations reveal that formation of complexes results in decrease in
      antibacterial activity of cephradine and MIC values are increased.

PMID- 16414568
TI  - Synthesis of some phenacyl derivatives of 1-methyl-7-methoxy-beta-carboline and
      their behavioural study.
AB  - In the present study two phenacyl derivatives of Harmaline; 2-(7-Methoxy-1-methyl
      1,3,4,9-tetrahydro-beta-carbolin-2-yl)-1-(3-nitro-phenyl)-ethanone and 1-(3,4
      Dihydroxy-phenyl)-2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)
      ethanone were synthesized and evaluated for their effect on behaviour of mice,
      only meta-nitro phenacyl derivative showed activity, which can be compared with
      parent compound.

PMID- 16414569
TI  - The effect of centrally acting drug chlorpromazine on the secretion of prolactin
      in the lizard, Uromastix hardwickii.
AB  - This investigation deals with the effect of chlorpromazine, on Uromastix
      hypophyseal prolactin. Administration of the doses 0.125, 0.25, 0.5 and 1 mg
      chlorpromazine per 3 days per animal resulted in a significant increase pigeon
      crop-sac response (p<0.01). The degree of proliferation of crop-gland showed a
      dose dependent threshold. Chlorpromazine binds to the target cell specific
      receptors of PRL and GH, both at the same time.

PMID- 16414570
TI  - Biochemical studies on marine fish oil part-I: effects of fish oil and lipid
      lowering drugs on HDL/LDL cholesterol levels.
AB  - Omega-3 fatty acids present in fish oil are potent cholesterol lowering agents.
      This fact has drawn our attention to investigate their effects alone and in
      combination with competitive inhibitors, (hydrooxymethylglutaryl coenzume-A
      reductase). The naturally occurring omega-3 fatty acids i.e., polyunsaturated
      fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      in fish oil have been proved as anticholesterolemic agents. In order to observe
      their actions as lipid lowering agents, the present study has been carried out
      which deals with the synergistic effect of fish oil with that of Lovastatin and
      Gemfibrozil.

PMID- 16414571
TI  - Clinical investigations of skeletal fluorosis in children of Manga Mandi in
      Pakistan.
AB  - In July 2000 about 124 children were detected suffering from skeletal fluorosis
      at Manga Mandi near Lahore. They were drinking high fluoride (maximum level 29
      ppm) containing water. We have studied various biochemical parameters in serum,
      including alkaline phosphatase, calcium and inorganic phosphorus. These levels
      were compared with the levels of those children who were the brothers and/or
      sisters of the patients (patient control) and had a dental fluororsis of varying
      degree. These levels were also compared with the serum levels of normal children
      (normal control). Serum samples were analyzed using standard kits of Boringer
      Mannham and Randox. Serum alkaline phosphatase levels of patients, patient
      control and normal control were 291.68 +/- 121.06 (mean +/- SD, n=8), 196.58 +/-
      45.71 (n=10) and 144.85 +/- 39.77 (U/L) respectively. Serum calcium levels of
      patient, patient control and normal control were 1.44 +/- 0.08, 1.41 +/- 0.14 and
      1.28 +/- 0.13 (m.mol/L) respectively. Serum inorganic phosphorus levels of
      patient, patient control and normal control were 1.55 +/- 0.08, 1.65 +/- 0.09 and
      1.69 +/- 0.04 (m.mol/L) respectively. These results enable us to conclude that
      blood calcium and phosphorus may play a major role for the determination of
      skeletal fluorosis whereas alkaline phosphatase may be having a minor importance.

PMID- 16414572
TI  - Effect of moisture on the stability of packaged paracetamol tablet formulations.
AB  - The stability of four commercial brands of packaged paracetamol tablet
      formulations stored at 25 +/- 1 degrees C and 75 +/- 2% RH for a period of six
      months has been studied and the effect of moisture on the degradation of
      paracetamol has been evaluated. PVC/PVDC/Al foil and polycoated paper packagings
      offer maximum protection to paracetamol tablets against moisture induced
      degradation. Moisture transmission of polymeric material appears to decrease with
      an increase in drug concentration and hence a relatively slow rate of degradation
      under controlled conditions.

PMID- 16414573
TI  - Evaluation of hydrophobic materials as matrices for controlled-release drug
      delivery.
AB  - The present study was undertaken to evaluate the effect of different insoluble
      and erodable wax-lipid based materials and their content level on the release
      profile of drug from matrix systems. Matrix tablets of theophylline were prepared
      using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol
      and glyceryl monostearate as rate-retarding agents by direct compression process.
      The release of theophylline from these hydrophobic matrices was studied over 8
      hours in buffer media of pH 6.8. Statistically significant difference was found
      among the drug release profile from different matrices. The release kinetics was
      found to be governed by the type and content of hydrophobic materials in the
      matrix. At lower level of wax matrices (25%), a potential burst release was
      observed with all the materials being studied. Bees wax could not exert any
      sustaining action while an extensive burst release was found with carnauba wax at
      this hydrophobic load. Increasing the concentration of fat-wax materials
      significantly decreased the burst effect of drug from the matrix. At higher
      hydrophobic level (50% of the matrix), the rate and extent of drug release was
      significantly reduced due to increased tortuosity and reduced porosity of the
      matrix. Cetostearyl alcohol imparted the strongest retardation of drug release
      irrespective of fat-wax level. Numerical fits indicate that the Higuchi square
      root of time model was the most appropriate one for describing the release
      profile of theophylline from hydrophobic matrices. The release mechanism was also
      explored and explained with biexponential equation. Application of this model
      indicates that Fickian or case I kinetics is the predominant mechanism of drug
      release from these wax-lipid matrices. The mean dissolution time (MDT) was
      calculated for all the formulations and the highest MDT value was obtained with
      cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be
      attributed to some level of swelling and erosion within this matrix at lower fat
      wax level which is also supported by release exponent values and Fickian fraction
      release against time profile of this agent. The results generated in this study
      showed that proper selection of these hydrophobic materials based on their
      physico-chemical properties is important in designing wax matrix tablets with
      desired dissolution profile.

PMID- 16414574
TI  - Hypoglycemic potential of tablet Metformin 500 mg (Glucophage & Metphage): a
      pharmacological end point evaluation.
AB  - Quantitative determination of pharmacological response or clinical end point
      study is essential for successful evaluation of clinical pharmacology and
      Bioavailability/ Bioequivalence issues. Stride has been made for proper selection
      of a quality drug product from the various available therapeutic, which is the
      prime responsibility of Health care provider and specially pharmacist. Study was
      conducted in respect to investigate the Pharmacodynamics response, differences
      and individual variation of oral, Metphage (Metformin 500 mg tablet) as a test
      formulation manufactured by Efroze Chemical Industries (Pvt.) Ltd. and Glucophage
      (Metformin 500 mg tablet) as a reference formulation manufactured by Merck
      Marker. Blood glucose levels/hypoglycemic effect produced by both formulation
      were studied under cross over trial with respect to placebo/control treatment and
      result were discussed accordingly. There were no hypoglycemic episodes requiring
      medical intervention and/or pharmacologic therapy so the patients can easily
      manage it. Results of the study clearly suggest that formulation manufactured by
      Efroze Chemical Industries (Pvt.) Ltd. is near to the standard formulation and
      produced comparable results. No significant differences in pharmacodynamics was
      observed, however, minor differences might relate with inter individual variation
      in human volunteers and in different formulation as well as different
      pharmaceutical unit. Although this data assure the ultimate quality of Metformin
      500 mg tablet manufactured by Efroze Chemical Industries (Pvt.) Ltd. but every
      Generic equivalent should be studied for assurance of safety and efficacy because
      life of patient is a matter of concern. Such type of study would provide better
      evaluation of the performance of a drug from a dosage form.

PMID- 16414575
TI  - Isolation and biochemical characterization of mutacin VSM43 isolated from human
      oral Streptococcus mutans VSM43.
AB  - Bacteriocins produced by mutans streptococci are known as mutacins. Streptococcus
      mutans VSM43 isolated from human clinical oral cavity was screened for the
      production of mutacin. It can inhibit the growth of other mutans streptococci,
      many other gram-positives and some gram-negative bacteria. Average size of the
      inhibitory zone ranged between 12-20mm. The inhibitory activity could not be
      related to organic acids, bacteriophages and hydrogen peroxide. Mutacin VSM43 was
      protease sensitive, remained active within a pH range of 2-8, and lost activity
      after heating at 100 degrees C for 30 min. Mutacin VSM43 was dialyzable through
      dialysis membrane (pore size 12,000 Da). A titre of 1280 arbitrary/activity units
      per ml (AU/mL) was shown against Staphylococcus aureus AB211. Lacuna frequency
      percentage (LF%) against Streptococcus mutans VSMD and Staphylococcus aureus
      AB211 was 37% and 49% respectively. We are convinced mutacin VSM43 may be a
      parallel candidate for use against dental caries.

PMID- 16414577
TI  - Stability of local and imported NDV vaccine under different storage conditions.
AB  - The present study has been done to evaluate the efficacy of vaccine during
      manufacturing, storage and distribution under fluctuation of temperature as the
      vaccines are very susceptible to temperature. The results showed that New castle
      disease virus induce infections in developing embryos that lead to death of
      embryo with few exceptions. Further infection is more rapidly fatal when the
      inoculated embryos are young, when the quantity of virus introduce is large and
      when the required incubation temperature is above 37 degrees C. Comparison of
      table 4 and 5, and graph 4 indicate that no significant difference was found in
      the viral content (HA) of local and imported vaccines before and after
      inoculation, when analyzed through ANOVA and 5% level of significance. Comparison
      of Table 6, 7 and 8 as well as Fig. 5 indicate that the end point of EID50 (local
      vaccine) decreases with the length of channel of distribution or we can say that
      these are inversely proportional to each other.

PMID- 16414576
TI  - Similar pattern of inhibition of tryptophan pyrrolase activity by fluoxetine
      hydrochloride in both sexes of rats.
AB  - Compounds targeting the individual enzymes of kynurenine-nicotinamide pathway
      have led to new neuropharmacological concepts and provide novel opportunities for
      therapeutic intervention. Tryptophan pyrrolase (Tryptophan-2, 3-dioxygenase; EC
      1.13.11.11), a metalloprotein, is the first and rate limiting enzyme of the most
      important pathway for tryptophan metabolism via kynurenine-nicotinamide pathway
      in the liver and therefore plays a key role in regulating the physiological flux
      of tryptophan in to relevant metabolic pathways like synthesis of
      neurotransmitter, serotonin in the brain. Fluoxetine, a clinically proven
      antidepressant, have shown statistically significant inhibition of hepatic
      tryptophan pyrrolase activities (holo, total and apo form) in both the sexes of
      rats at 10 & 30 mg/kg doses. Despite elevated holo-enzyme form of tryptophan
      pyrrolase in female rats, we have found similar inhibition of tryptophan
      pyrrolase activity by fluoxetine hydrochloride in both male and female rats. The
      results are discussed in relation to gender differences in the enzyme activity
      and its possible role in pathophysiology of depression in females.

PMID- 16414578
TI  - Statistical evaluation of the N-bromosuccinimide and Iodine as titrimetric
      methods for estimation of vitamin C in orange juice and pharmaceutical
      preparations.
AB  - N-bromosuccinimide (NBS) and Iodine solution have been used separately for
      oxidation of vitamin C in orange juice and pharmaceutical preparations. The
      quantitative results obtained by the two methods have been statistically
      evaluated for evidence of systematic difference, if any, between the two methods.
      The t-test has shown that titration with dilute solution (0.0022 M) of NBS has
      produced better results as compared to Iodine method. On the contrary a
      concentrated Iodine solution (0.0828 N) gave good results.

PMID- 16414579
TI  - The effect of varying concentrations of ergometrine maleate on the pituitary
      prolactin of the lizard, Uromastix hardwickii.
AB  - Present study deals with the effect of ergometrine maleate on prolactin (PRL) of
      Uromastix pituitaries. Administration of 0.02, 0.04 and 0.06 mg/day/animal
      ergometrine maleate for 3 days to individuals of 3 respective groups resulted in
      decreased pigeon crop-sac diametric response. Intramuscularly treated pituitaries
      showed more PRL inhibition than the pituitaries of animals treated intravenously.

PMID- 16414580
TI  - Antimicrobial spectrum, production and mode of action of staphylococcin 188
      produced by Staphylococcus aureus 188.
AB  - Staphylococcus aureus 188 has been shown to produce bacteriocin-like inhibitory
      substance known as staphylococcin 188. It has a broad-activity spectrum against
      Micrococcus luteus, Streptococcus pneumoniae, Streptococcus faecalis,
      Streptococcus viridans, Corynebacterium diphtheriae and several staphylococcus
      species. The arbitrary unit of staphylococcin 188 against Micrococcus luteus was
      1280 AU/mL. Its production with simultaneous measurement of activity was
      monitored and was found to produce maximum amount of staphylococcin after 7 hours
      of incubation. Mode of action of the staphylococcin 188 on the sensitive cells
      was bactericidal rather than bacterioloytic.

PMID- 16414581
TI  - Bioactivity studies of the individual ingredients of the Dashamularishta.
AB  - The bioactivity studies of the individual ingredients of Dashamularishta--a
      classical Ayurvedic preparation were done with the aqueous extracts of the
      individual ingredients. The Aegle marmelos Correa. exhibited severe toxicity to
      the brine shrimp (BST) nauplii, wheat rootlet growth (WRG) inhibition bioassay
      and lettuce seed germination (LSG) bioassay. It exhibited no inhibition to the
      growth of PPR and Reo virus in vero cell line. The Oroxylum indicum exhibited
      moderate toxicity to the BST and WRG, but it is not toxic to the LSG. It
      exhibited no inhibition to the growth of PPR and Reo virus. The Stereospermum
      suaveolens exhibited severe toxicity to the BST and LSG, but it is not toxic to
      the WRG. It exhibited total inhibition to the growth of Reo virus, but it has not
      effect on the PPR virus. The Premna integrifolia showed severe toxicity to the
      BST, but it was not toxic to the WRG and LSG. It exhibited no inhibition to the
      growth of PPR and Reo virus. The Gmelina arborea exhibited severe toxicity to the
      BST and WRG, but it is not toxic to the LSG. It exhibited no inhibition to the
      growth of PPR and Reo virus. The Solanum xanthocarpum showed mild toxicity to the
      BST, WRG and LSG. It exhibited 75% inhibition to the growth of Reo virus. The
      Solanum indicum showed no toxicity to the BST, WRG and LSG. It exhibited 75%
      inhibition to the growth of PPR virus. The Desmodium gangeticum showed no
      toxicity to the BST, but moderate toxicity to the WRG and LSG. It exhibited total
      inhibition to the growth of PPR virus. The Uraria lagopoides showed no toxicity
      to the BST, WRG and LSG. It exhibited total inhibition to the growth of Reo
      virus. The Tribulus terrestris showed no toxicity to the BST, but showed moderate
      toxicity to the WRG and LSG. It exhibited 75% inhibition to the growth of both
      PPR and Reo virus.

PMID- 16414582
TI  - Chromatographic study of photolysis of aqueous cyanocobalamin solution in
      presence of vitamins B and C.
AB  - Aqueous cyanocobalamin solutions (pH 1-7) have been photolysed in the presence of
      individual B (thiamine HCl, riboflavin, nicotinamide and pyridoxine HCl) and C
      (ascorbic acid) vitamins with visible light. The degraded solutions were
      subjected to thin-layer chromatography using several solvent systems and the Rf
      values of the vitamins and their photoproducts were determined. The major
      photoproducts have been identified by comparison of their Rf values with those of
      the authentic compounds. Cyanocobalamin leads to the formation of
      hydroxocobalamin. Thiamine HCl gives rise to 4-methyl-5-(Beta-hydroxyethyl)
      thiazole and 2-methyl-4-amino-5-hydroxymethyl-pyrimidine in trace amounts whereas
      riboflavin degrades extensively to formylmethylflavin and lumichrome, and to a
      smaller extent to lumiflavin and carboxymethylflavin. Ascorbic acid is oxidized
      to dehydroascorbic acid. Nicotinamide and pyridoxine HCl do not undergo any
      degradation. The extent of degradation depends upon the pH.

PMID- 16414583
TI  - Comparative lipid profile studies in cardiac and diabetic conditions.
AB  - Lipid profile in cardiac patients (myocardial infarction, angina pectoris,
      coronary heart disease, ischaemic heart disease), diabetic patients and normal
      humans was investigated. Total serum cholesterol, high density lipoprotein
      cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides,
      blood glucose, calcium, potassium and sodium were determined, employing
      established methods and procedures. Higher level of total cholesterol, LDL-C and
      triglyceride were found in both cardiac and diabetic patients, however, cardiac
      patients had much lower level of HDL-C as compared to normal humans. Age wise
      comparison revealed that level of total cholesterol; triglyceride and LDL-C were
      elevating while the level of HDL-C were decreasing with the age in cardiac and
      diabetic patients. Sex wise comparison showed that females had higher HDL-C level
      than males and therefore had fewer incidences of heart diseases. The level of
      Ca++, K+ and Na+ were similar in all age groups and sexes. No significant
      elevation in the level of these electrolytes was discovered.

PMID- 16414584
TI  - Effect of diazepam on the CNS excitation and behavioural changes induced by
      harmaline and its newly synthesized analogues.
AB  - The neuropharmacologic profile of harmala alkaloids has been studied and found to
      have central effects like convulsions, catalepsy, or altered startle response. In
      number of studies the effects of diazepam, on harmaline and other beta carboline
      containing compounds-induced tremors were investigated. The present study was
      undertaken to examine the effect of diazepam on pretreated animals with harmaline
      and its synthesized phenacyl and coumarine analogues. Diazepam successfully
      inhibited the tremor and convulsions and attenuated the other behavioural
      response produced by harmaline and its derivatives.

PMID- 16414585
TI  - Investigation of the active constituents of Portulaca oleraceae L.
      (Portulacaceae) growing in Jordan.
AB  - The phytochemical analysis of the fresh aerial parts of Portulaca oleracea
      (Portulacaceae), growing in Jordan, using conventional chromatographic procedures
      resulted in the isolation of Beta-sitosterol, Beta-sitosterol-glucoside, N,N'
      dicyclohexylurea, and allantoin. The last three compounds were isolated for the
      first time from this plant. The structure elucidation of these compounds was
      attained by the use of spectral data (UV, IR, MS, 1H-, 13C- and 2D-NMR), X-ray
      crystallography and by comparison with authentic samples.

PMID- 16414586
TI  - Kinetic studies on Zingiber officinale.
AB  - The present investigation deals with the isolation, purification and
      characterization of gingerol, the major pungent constituent of ginger (Zingiber
      officinale) and its kinetic of extraction using a number of organic solvents. The
      characterization was carried out through GC and GC-MS. Gingerol has been assayed
      in the plant material during extraction with various solvents by a HPLC method.
      In order to develop a relationship between solvent characteristics such as
      viscosity and dielectric constant and the rates of extraction, the kinetics of
      extraction of gingerol has been studied by using twelve different solvents in
      order to evaluate the solvent efficacy in the extraction processes. It has been
      observed that both solvent viscosity (1/v) and dielectric constant (epsilon) show
      a linear relationship with the rates of extraction (k). An increase in solvent
      viscosity leads to a decrease in the rates of extraction, similarly an increase
      in dielectric constant also leads to a decrease in the rates of extraction. This
      appears to be largely due to an unionizable character of gingerol which does not
      interact with polar solvents. Thus solvent viscosity and dielectric constant both
      play an important role in the choice of solvents for the extraction of gingerol.
      Solvents with relatively low viscosity and dielectric constant are more suitable
      for the extraction of gingerol from plant material.

PMID- 16414587
TI  - Pharmacokinetic differences of some generic tablet gliclazide 80 mg on Pakistani
      population.
AB  - The goal of rational drug therapy is to produce a desired pharmacological
      response in an acceptable and predictable manner while minimizing the occurrence
      of undesired events. The Pharmacokinetics of different generics of tablet
      gliclazide 80 mg was investigated on healthy (10 x 2), Pakistani subjects. For
      this exploration an open-label, randomized, two-period crossover (Balanced in
      Complete Block Design) study, was conducted The out come of the said study
      suggests that all generics were found analogous regarding pharmacokinetic
      behavior in-spite of having different excipients, concentration of excipients,
      sources of raw material, manufacturing process, machinery, resources and also
      inter individual variation of the study. Results of the study also undoubtedly
      advocate that generics manufactured in different manufacturing units of Pakistan
      are near to the standard formulation and produce comparable results. No
      significant differences in pharmacokinetics parameters were observed, however,
      minor differences might narrate with inter individual variation in human
      volunteers and in different generic as well as different pharmaceutical unit.

PMID- 16414588
TI  - Roxithromycin antagonism with essential and trace elements.
AB  - In order to ascertain the role of various essential and trace element
      complexation on the antibacterial activity of various macrolide antibiotics, the
      synergistic or antagonistic behavior of roxithromycin metal complexes have been
      studied and compared with the parent drug. Metal complexes of roxithromycin with
      magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and
      cadmium have been investigated for their antibacterial activity and compared with
      roxithromycin by observing the changes in minimum inhibitory concentration (MIC)
      and by measuring the zone of inhibition of complexes against both Gram-negative
      and Gram-positive microorganisms. Various microorganisms used were Staphylococcus
      aureus, Enterococcus faecalis, Escherichia coli, Salmonella typhi, Proteus
      vulgaris, Shigella dysentery, Klebsiella pneumoniae and Staphylococcus
      epidermidis. For MIC observation, serial dilution method was employed and zone
      sizes were determined by diffusion disk method. Our investigations divulge that
      formation of roxithromycin complexes results in antagonistic behavior against few
      microorganisms where in MIC is increased with respect to the parent drug, while
      against most of the microorganism, there was no effect on the MIC of the
      roxithromycin metal complexes with respect to parent roxithromycin.

PMID- 16414589
TI  - The effects of Isoniazid on the osmotic resistance of lacertilian erythrocytes.
AB  - Osmotic fragility of erythrocytes is increased by a number of commonly used
      analgesics, antimicrobial and antimalarial drugs, resulting in drug-induced
      hemolytic anemia. Study of erythrocyte osmotic fragility of control and test
      blood was determined after 5,10 and 15 days of 0.06 mg/ml/day Isoniazid (INH)
      administration to test subjects. Isoniazid treated subjects exhibited greater RBC
      fragility than control in 0.1 to 0.3 hypotonic solutions. Control subjects
      exhibited only 3 per cent destruction in 0.4 per cent saline; whereas test
      subjects exhibited 12 and 11 per cent destruction on day 5, and 15 in 0.4 per
      cent concentration of saline, while 10,13 and 15 per cent destruction in 0.5 per
      cent saline. The study indicated that following prolonged administration of
      Isoniazid a great number of osmotically fragile RBCs enter the blood stream.

PMID- 16414590
TI  - Thermodynamic dissociation constant studies of caffeine at different temperatures
      and in organic water solvent mixture.
AB  - Thermodynamic dissociation studies have been carried out potentiometrically at
      various temperatures from 25 to 50 degrees C and in 10, 20, 30 and 40% v/v
      dioxane-water solvent mixture at 25 degrees C. The influence of temperature and
      nature of solvent on dissociation equilibria of caffeine is being investigated. A
      computer program in GW-BASIC has been used to calculate the pK values.

PMID- 16414591
TI  - Application of Limulus Amebocyte Lysate (LAL) test for detecting endotoxin
      (pyrogen) in large volume parenterals.
AB  - Screening of twenty five large volume parenterals including dextrose,
      electrolytes, mannitol, metronidazole infusions, haemodialysis solution, water
      for injections and distilled water for the determination of pyrogen using Limulus
      Amebocyte Lysate (LAL) test has been carried out. Out of different preparations
      only one metronidazole injection exhibited positive LAL test, which was found
      pyrogen free with USP rabbit pyrogen test.

PMID- 16414592
TI  - Antihypertensive and metabolic effects of verapamil: role of Na-K-ATPase and
      electrolytes homeostasis in male and female rats.
AB  - Calcium channel antagonists have been shown to be effective in the management of
      coronary vascular diseases. Although initially restricted to the treatment of
      angiopectoris could prevent cardiovascular complication in patients with
      diabetes. In view of a possible role of electrolytes in the therapeutic effects
      of verapamil, the present study concern effects of verapamil on serum, red cell,
      tissue electrolytes and Na-K-ATPase activity in both male and female rats.
      Verapamil (30 mg/kg body weight) was administered intraperitoneally to the test
      group. Control group received same volume of deionize water. A slight decreased
      Na-K-ATPase activity was observed in both sexes. Verapamil treatment decreases
      serum sodium and magnesium levels in both male and female rats. However serum
      potassium was slightly increased in both sexes. Verapamil treatment in red cells
      decreases sodium and increases potassium content in both sexes. Verapamil
      administration decreases sodium and calcium content in heart, liver and kidney
      tissues in both sexes, whereas an increased content of potassium and magnesium
      was observed in these tissues except liver in which the magnesium content was
      slightly decreased in both male and female rats. The results showed that the
      changes in electrolyte levels are more pronounced in female than in male rats.
      The results reported in the present study suggests that the drug has been shown
      to inhibit aldosterone biosynthesis to a variable degree. Although the
      antihypertensive effect of verapamil is considered to be mainly due to its
      vasodilation or by inhibition of vasoconstriction. It is suggested that verapamil
      lower blood pressure by correcting a pathophysiological derangements of
      electrolytes present in hypertension. The cellular mechanism involved is the
      altered serum, intracellular, tissue electrolytes and ATPase activity.

PMID- 16414593
TI  - Antinociceptive activity of methanolic extracts of St. John's Wort (Hypericum
      perforatum) preparation.
AB  - The analgesic effect of St. John's Wort plant preparation was evaluated using
      chemically induced pain models in adult albino mice. The intraperitoneal (i.p.)
      administration of 30-100 mg/kg of the preparation produced significant analgesic
      effect (75%) in acetic acid induced writhing and formalin licking tests. Based on
      its inhibitory effects on acetic acid induced writhes and both phases of the
      formalin test, the plant preparation seems to have central and peripheral
      analgesic properties. Its effect was found twice more potent than ibuprofen (100
      mg/kg), a standard reference drug, in the acetic acid induced writhing test.

PMID- 16414594
TI  - Effects of human chorionic gonadotropin (hCG) on pituitary prolactin (PRL) in the
      lizard, Uromastix hardwickii.
AB  - A consideration of the data indicates that 45 IU human chorionic gonadotropin
      (hCG) treated lizard pituitaries, extracted after 30 and 60 minutes gave a mean
      crop-sac diametric response of 2.15 cm and 2.13 cm respectively in pigeons. The
      role of hCG in accelerating the synthesis of pigeon's milk is extra ordinary, and
      it seems that hCG exhibits this effect via lizard pituitary lactotrophs.

PMID- 16414595
TI  - Evaluating the effects of plasticizer interactions with HPMC on the tack-behavior
      of polymer film-forming coating solutions.
AB  - Tack is a concept that is widely used to describe the forces or energies involved
      in the separation of two parallel surfaces initially in contact through an
      intervening thin liquid film. The tackiness may cause tablets to stick with each
      other or to the walls of the coating apparatus. In this study, the HPMC coating
      solutions were evaluated for their tackiness and the effects of interactions
      between the polymer and plasticizers on the tack behavior of HPMC film-forming
      coating solutions were investigated, using type TA-XT2 texture analyzer. It was
      found that experimental factors such as the contact time, rate of separation and
      volume of the film-forming test solution could effectively influence the
      magnitude of tack behavior. Moreover, up to certain levels, the addition of
      plasticizers such as PEG 400 & 1000 and of triacetin caused a reduction in the
      tack value of the polymer solutions. It was concluded that in general, the
      tackiness depended upon the molecular weight and/or type and concentration of a
      plasticizer. The efficiency of plasticizers used to reduce the tackiness of HPMC
      solutions ranked as PEG1000 > triacetin > PEG400.

PMID- 16414596
TI  - In vitro availability of glibenclamide in presence of antacids.
AB  - The in vitro availability studies of glibenclamide in presence of commonly used
      antacids are present in this paper. Glibenclamide is used for the treatment of
      Non-Insulin dependent diabetes mellitus. It is a sulfonylurea derivative.
      Antacids are prescribed to encounter gastric acidity etc. These studies were
      carried out in simulated gastric juice and in buffer of pH 7.4 at 37 and 48
      degrees C. Aluminum hydroxide, aluminum trisilicate, magnesium oxide, magnesium
      trisilicate, sodium bicarbonate, calcium carbonate, magaldrate and simethicone
      (2,4-dimethoxypolysiloxane) antacids were used in these studies. It has been
      observed that in case of magnesium oxide, magnesium trisilicate and sodium
      bicarbonate, availability of glibenclamide was enhanced while in rest of the
      antacids retarded the availability of glibenclamide.

PMID- 16414597
TI  - Lack of restraint-induced increases of brain serotonin metabolism in rats treated
      with spiperone: relationship with restraint-induced behavioral deficits.
AB  - Spiperone is a potent dopamine (DA) D2, serotonin (5-hydroxy tryptamine, 5-HT) 5
      HT(1A) and 5-HT(2A) antagonist. It is used clinically as an antischizophrenic
      compound. Previous studies have shown that a downregulation of somatodendritic 5
      HT(1A) receptor is involved in adaptation to stress. The present study was
      designed to investigate the effects of spiperone administration on behavioral
      adaptation to an episode of restraint stress and on brain serotonin metabolism.
      Spiperone was administered to rats at a dose of 0.25 mg/kg/ml two times a day for
      two days. Saline or spiperone treated rats were restrained for 2 h on day 2.
      Effects of restraint on food intake, water intake, growth rate, plus maze and
      open field activity were monitored on next day. All animals were killed after a
      restraint period of 2 h on the 3rd day. An episode of 2 h restraint decreased
      food intake, growth rate and water intake comparably in saline and spiperone
      treated rats. Open field activity was not altered by restraint stress or
      spiperone treatment. Plus maze activity decreased by restraint stress in saline
      but not spiperone treated rats. 5-HIAA levels increased in saline but not
      spiperone treated rats. The findings are discussed in the context of a role of
      serotonin and 5-HT(1A) receptor antagonism in adaptation to stress.

PMID- 16414598
TI  - Levofloxacin interactions with essential and trace elements.
AB  - Levofloxacin is (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-pipe
      razinyl)-7oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate
      and a fluorinated quinolone antibacterial agent extensively used against both
      Gram-positive as well as Gram-negative microorganisms. The in vitro release of
      levofloxacin has been studied in presence of metal ions like magnesium, calcium,
      chromium, manganese, ferric, ferrous, cobalt, nickel, copper, zinc and cadmium in
      simulated gastric juice, simulated intestinal juice and at blood pH. These
      studies were carried out using BP 2002 dissolution test apparatus at 37 degrees
      C. The availability of levofloxacin was found to be markedly retarded in the
      presence of all the metals studied.

PMID- 16414599
TI  - o-Phthalaldehyde based spectrophotometric determination of sulfonamides.
AB  - o-Phthalaldehyde (OPA) reacts with primary amino group in a compound in presence
      of a thiol (RSH) and in an alkaline medium to give a soluble product called
      isoindole. This is a fluorescent compound, yet it has been exploited for
      spectrophotometric study by measuring the absorbance at 340 nm which is the
      wavelength for excitation of the molecule. The spectrophotometric method has
      successfully been employed in the quantitative estimation of sulfonamides such as
      sulfadiazine, sulfanilamide and sulfamethoxazole, all containing a primary amino
      group. The detection ranges from 0.01 to 0.24 mg/ml of the active ingredient in
      different samples containing sulfonamides. The respective standard curves were
      linear in the given range and the relative standard deviation of the mean
      response factor ranged from 1.95-2.08%. 2-methyl-2-propane thiol (2MPT) has been
      used in the derivatization reaction for the formation of OPA-adduct and borate
      buffer of pH 10.0 has been used to maintain the medium alkaline.

PMID- 16414600
TI  - Serum lipids and lipoproteins in patients with documented coronary artery
      disease.
AB  - Levels of various lipoprotein subclasses can provide useful information on
      coronary artery disease (CAD) risk status, even when traditional risk factors are
      known. Elevated serum level of lipids, lipoproteins and lipoprotein (a) have been
      identified as risk factor for atherosclerosis resulting in coronary artery
      disease, cerebrovascular disease, peripheral vascular disease and venous
      thromboembolism. The objective of this study is to evaluate the levels of serum
      lipids, lipoprotein and lipoprotein (a) in-patients suffering from documented
      coronary artery disease and normal healthy subjects. A case control study was
      conducted to evaluate the levels of lipid, lipoprotein and lipoprotein (a) in
      patients from our local population suffering from documented coronary artery
      disease. The present study was earned out in Dr. HMI Institute of Pharmacology &
      Herbal Sciences in collaboration with National Institute of Cardiovascular
      Diseases, Karachi from January 2001 to June 2001. One hundred and fifty persons
      were included in this case control study. Out of these one hundred were patients
      suffering from documented (coronary angiography done 4 month before the study)
      coronary artery disease (mean age 46.38 +/- 1.38, 18 females and 82 males). 50
      normal healthy subjects (mean age, 44.86 +/- 1.15, 2 females and 48 males) had no
      history of IHD ever before. Their serum lipid, lipoprotein and lipoprotein (a)
      were estimated and compared.

PMID- 16414601
TI  - Spectral study of photolysis of aqueous cyanocobalamin solutions in presence of
      vitamins B and C.
AB  - The UV and visible absorption characteristics of B and C vitamins have been
      studied in the pH range 2.0-7.0. The overlapping of the absorption bands of
      thiamine hydrochloride, nicotinamide, pyridoxine hydrochloride and ascorbic acid
      with cyanocobalamin in the UV region and those of riboflavin in the UV and
      visible region may influence the rate of photolysis of cyanocobalamin in aqueous
      solution due to mutual interaction on exposure to light. The spectral variations
      in cyanocobalamin solutions at pH 2.0-7.0 containing appropriate amounts of the
      individual B/C vitamins, during photolysis, have been monitored and the effect of
      pH on the rates of reaction has been discussed. The rates of photolysis, in
      general, decrease with an increase in pH probably due to gradual deprotonation of
      cyanocobalamin cation (B12 H+) as indicated by the magnitude of absorbance loss
      at the maxima at 361 and 550 nm.

PMID- 16414602
TI  - The inherent rhythmic contraction property of penile tissue in sexually active
      adult male rats and the effect of sildenafil citrate (Viagra): an in vitro pilot
      study.
AB  - Isolated human cavernosal muscles and those of various animals have extensively
      been studied for understanding the causes and treatment of erectile dysfunctions.
      Usually these tissues are first pretreated with suitable drugs, i.e.
      Noradrenaline (N-Adr), phenylephrine, carbacol, KCl and nicorandil etc. to induce
      resting tone or contractions in them, followed by the application of relaxing
      drugs like sildenafil. We undertook this project to show first of all that these
      penile tissues were capable of generating rhythmic contractions if properly
      treated with suitable drugs, either alone or in combination, and then to study
      the properties of these induced tensions and/or contractions. Attempt was also
      made to study the effects of sildenafil on various parameters of these
      contractions. Pretreatment of the tissues with atropine and N-Adr both initiated
      rhythmic contractions, the atropine effect being more potent (2-1/2 times larger)
      on the contraction rate while N-Adr effect being significantly higher on the
      resting tone. Atropine also increased the contraction rate and strength of
      contractions in the washed tissues or when it was applied in combination with N
      Adr. Ach had no effect on the rate and strength of contractions in atropine
      treated tissues but it decreased contraction rat in washed tissues or when
      applied in combination with sildenafil. Sildenafil decreased the rate and
      strength of contractions in all the tissues pretreated with atropine or N-Adr or
      in the washed tissues. The effect of sildenafil was more potent on atropine
      treated tissues than those on N-Adr treated ones. Atropine, Acetylcholine (Ach)
      and sildenafil had no effect on the resting tone of the tissues while N-Adr
      significantly increased the resting tone in both the atropine treated and washed
      tissues.

PMID- 16414603
TI  - Urinary tract infections associated with multidrug resistant enteric bacilli:
      characterization and genetical studies.
AB  - Urinary tract infections (UTIs) are among the most commonly prevalent infections
      in clinical practice. Escherichia coli is the causative agent in about 85% of
      community-acquired UTIs, followed by Klebsiella that accounts for 6 to 17% of
      such infections. Present study is based on the isolation-identification and
      antibiotic resistance pattern of about 60 indigenous bacterial isolates from UTI
      patients. Prevalence rates were consistent with those from major recent studies
      reported in the literature, i.e. 73% isolates were identified as E. coli, 16% as
      K. pneumoniae and 11% as Proteus sp. Bases of identification included morpho
      cultural and biochemical characteristics. To assess the breadth of multidrug
      resistance among these isolates, culture medium incorporation method was employed
      using ampicillin, fosfomycin, chloramphenicol, tetracycline, and three
      aminoglycosides (kanamycin, gentamicin, and streptomycin). Of these isolates, 30%
      offered multidrug resistance to three or more agents. Among multidrug resistant
      isolates, 100% were resistant to ampicillin, 47% to streptomycin, 41% to
      chloramphenicol, gentamicin and tetracycline, 35% offered resistance to kanamycin
      while only 6% showed resistance to fosfomycin. After curing treatment with
      acridine orange, some of the isolates lost their resistance, thereby indicating
      the extrachromosomal location of the resistance determinants. Plasmid DNA
      (bearing multidrug resistant genes) was isolated from the uncured cells, and was
      stably transformed into the competent cured recipient cells.

PMID- 16414604
TI  - Diseases causing biochemical changes during pregnancy in the population of
      Karachi.
AB  - Malnutrition and population growth rate are the basic problems is south Asian
      countries, mainly Pakistan, Bangladesh, India etc. This situation becomes serious
      when a woman becomes pregnant. In this research work 30 pregnant women belonging
      to middle and lower middle class of 25 to 35 years of age were examined at Abbasi
      Shaheed Hospital, Karachi. Most of the women showed malnutrition and iron
      deficiency anemia, which increased gradually with the passage of time. Above
      mentioned problem is unmistakable related to socioeconomic factors.

PMID- 16414605
TI  - Divalent cation induced DNA-zwitterionic vesicle formulation compacted for gene
      delivery: thermodynamic aspects.
AB  - Complexes between nucleic acids and phospholipid vesicles have been developed as
      stable non-viral gene delivery vehicles. Currently employed approach uses
      positively charged lipid species and a helper zwitterionic lipid, the latter
      being applied for the stabilization of the whole complex. However, besides
      problematic steps during their preparation, cationic lipids are toxic for cells.
      Present work describes some energetics issues pertinent to preparation and use of
      neutral lipid-DNA self-assemblies, thus avoiding toxicity of lipoplexes.
      Differential scanning calorimetry data showed stabilization of polynucleotide
      helix upon its interaction with liposomes in the presence of divalent metal
      cations. It is thus possible to suggest this self-assembly as an improved
      formulation for use in gene delivery.

PMID- 16414606
TI  - EFFECT OF pH ON THE PHOTOSTABILITY OF SULPHACETAMIDE EYE-DROP SOLUTIONS.
AB  - The photolysis of aqueous solutions of sulphacetamide and sulphanilamide has been
      studied at pH 3-11. The rate of phatolysis appears to be the highest around pH
      5.0 and 3.0 for sulphacetamide and sulphanilamide respectively. The log k-pH
      profiles of both compounds in the buffered and unbuffered solutions are
      presented. Various buffer ions e.g. citrate and phosphate catalyase the
      photodegradation reactions. Sulphacetamide eye-drop solutions prepared at pH 7 to
      9 have ideal stability and clinical efficacy.

PMID- 16414607
TI  - Two dimensional NMR studies of chaksine.
AB  - Assignments of (1)H and (13)C-nmr signal of chaksine were made with the help of
      two dimensional (1)H-(1)H homonuclear and (1)H (13)C heteronuclear shift
      correlation.

PMID- 16414608
TI  - Screening of clonidine effect on brain acetylcholine content, anticonvulsant and
      local anaesthetic properties.
AB  - Clonidine, a potent centrally acting antihypertensive drug was screened for
      effect on " free " and " bound " acetylcholine (Ach) in brain of morphine
      dependent and morphine withdrawal rats, anticonvulsant activity and morphine
      withdrawal rats, anticonvulsant activity and local anaesthetic activity. " Free "
      and " total " Ach content in normal (non-dependent) animals as well as in animals
      dependent to morphine was not changed by clonidine. Naloxone produced abstinence
      syndrome in dependant rats with highly significant increase in " free " Ach.
      Clonidine pretreatment decreased the rise of " free " Ach content produced by
      naloxone. It failed to show any anticonvulsant effect against maximal
      electroshock convulsions in rats, however, it exhibited significant local
      anaesthetic activity. Diuresis, piloerection and convulsions were observed with
      higher doses of clonidine.

PMID- 16414609
TI  - Revised phytochemical study of arnebia hispidissima.
AB  - Chemical investigations into the constituents of the roots of Arnebia
      hispidissima have yielded 3 new naphthaquinone which possess antibiotic and
      anticancerous properties. A flavonoid, characterised as vitexin, has been
      isolated from the fresh flowers of Arnebia hispidissima. A dye, commonly known as
      RATANJOT in Indo-Pakistan medicine, is obtained from the roots of A.
      hispidisaima. Other compounds, alkannin monoacetate, alknannin alpha
      dimethylacrylate, (+/-) - alkannnin and three new naphthaquinones having
      antibiotic and anticancerous activities have been reported from its roots 1-4.
      Phytochemical studies into the constituents of fresh flowers of A. hispidissima
      have been carried out for the first time. A flavonoid, characterised as vitexin,
      has been isolated.

PMID- 16414610
TI  - Reactions of sterols with pyridinium chlorochromate.
AB  - Reaction of pyridinium chlorochromate with cyclohexanol and several C(3)-sterols
      have been investigated. It has been found that the equatorieal C(3)-sterols axe
      easily oxidised in good yield to give corresponding ketosteioids while the axial
      sterols give poor yields.

PMID- 16414611
TI  - Spectrophotometric method of determination of natural indoles by coloured
      complexes.
AB  - A new spectrophotometric method has been developed for quantitative determination
      of naturally occurring indoles via electron donor-acceptor complexes with
      chloranil. The method is simple, precise and convenient for routine laboratory
      work. The analysis of each indole can be carried out within half an hour.

PMID- 16414612
TI  - Bioavailability and disposition kinetics of rifampicin capsules.
AB  - Different drug manufactures claim better quality and bioavailability of the
      similar dosage from of a drug product. In view of this, bioequivalence on the
      basis of bioavailability and disposition kinetics of rifampicin capsules marketed
      under the brand names of Rifadin, Rifapin and Rimactane were investigated in
      normal human volunteers. Each drug was given orally and blood levels of active
      rifampicin at different times were measured by a microbiological assay procedure.
      The studies revealed that the absorption kinetics, bioavailability and
      disposition kinetics of three brands of rifampicin did not differ from each other
      significantly in human volunteers.

PMID- 16414614
TI  - Changes in e.C.g. And electrolytes during coronary ligation in anaesthetized cat.
AB  - The ligation of the coronary artery produces cardiac, and haemodynamic
      disturbances. Electrolytes disturbances were also noted during the assault
      (Harris et. al., 1954). In present experiments local cardiac ischaemia was
      produced by coronary ligation and changes in E.C.G. and electrolytes were noted
      at various stages. Pre-mature ventricular systoles and T wave inversion with an
      increase in K+ and decrease in Na+ was observed.

PMID- 16414613
TI  - Pharmacological screening of indigenous medicinal plants (iii).
AB  - The effects of the alcoholic extracts of fifteen indigenous plants have been
      studied on the isolated guineapig ileum preparations. Eleven extracts produced a
      spasmogenic effect, whereas, four extracts depicted a spasmolytic effect against
      acetylcholine.

PMID- 16414615
TI  - Inhibitor(S) of prostaglandin endoperoxide synthase and lipoxygenase activity in
      extracts of barley.
AB  - Aqueous extract of barley was found to inhibit PG endoperoxide synthase and
      lipoxygenase enzymes responsible for arachidonic acid metabolism. Only 6% (v/v)
      of aqueous extract produced 50% inhibition of PG endoperoxide synthase while five
      times more extract was required to produce 50% inhibition of lipoxygenase.
      Boiling barley extract did not destroy the ability of the extract to inhibit the
      enzymes. Fractionation of barley with organic solvents, petroleum ether,
      chloroform, ethylacetate and acetone exhibited selectivity in its action in that
      foamy layer formed during petroleum ether and ethyl acetate extraction inhibited
      PG endoperoxide synthase completely whereas lipoxygenase activity was only
      partially inhibited. These results suggest the presence of inhibitor(s) of
      arachidonic acid metabolism in extracts of barley.

PMID- 16414616
TI  - Phytochemical and antimicrobial screening of some plants used in saudi folk
      medicine.
AB  - Thirty-two plants species belonging to 22 families commonly used in Saudi folk
      medicine were subjected to phytochemical and antimicrobial screening. The results
      showed that sterols/triterpenes, flavonoids and tannins were the most common
      constituents. Volatile oils, volatile bases, coumarins, anthraquinones and
      cardiac glycosides were also detected. A variable range of antimicrobial activity
      was observed by the extracts and MIC's were determined wherever activity was
      noticed.

PMID- 16414617
TI  - Microbial contamination of pharmaceutical preparations.
AB  - Contamination of Pharmaceuticals with micro-organisms irrespective of being
      harmful or objectionable or nonpathogenic, can bring about changes in their
      physical characteristics, including the breaking of emulsions, the thinning of
      creams, Fermentation of syrups, and appearance of turbidity or deposit, besides
      producing possible off ordors and color changes.

PMID- 16414618
TI  - Review : mycotoxins in food (1) cereal grains and their products.
AB  - Fungal poisons have been known for many years but they have not been considered a
      major factor in human health problems until almost the last two decades.
      Epidemics of dry gangrene and various derangements of man was common feature in
      Europe from the 11th through the 16th centuries. A disease called holy fire was
      actually ergotism and was caused by a related group of alkaloids from the
      sclerotia of a mould Claviceps purpurea. The source of the ergot which contained
      the toxin was infested rye, which was ground into flour, baked and consumed by
      the affected persons (Forgacs and Carl, 1962).

PMID- 16414619
TI  - Synthesis of chlorpropamide-N1-(2, 3, 4, 6-tetra-O-acetyl-beta-D-glucuronide)
      under phase transfer catalyzed condition.
AB  - Chlorpropamide-N1-peracetyl glucoside was synthesized by a phase transfer
      catalysed method. The synthetic product was analysed by spectroscopic techniques
      (NMR and MS).

PMID- 16414620
TI  - Effect of diet on transaminase and arginase activities.
AB  - The composition of the diet greatly influences the enzyme activities of the
      liver. The effect of low carbohydrate diet on AST, ALT and arginase activities in
      liver and serum of rats was determined in the present study. Liver ALT and serum
      AST were significantly increased in animals fed on low carbohydrate diet, the
      activities of other enzymes remained unchanged.

PMID- 16414621
TI  - Stability-indicating assay of sulphacetamide in thermally degraded solutions.
AB  - A stability-indicating assay method for the determination of sulphacetamide in
      thermally degraded solutions is reported. The method is based on the difference
      in the absorption maxima of sulphacetamide and sulphanilamide at pH 4.0 and their
      simultaneous determination by a two component assay using the analytical
      wavelengths of 258 nm and 268 nm the reproducibility of the method lies within +/
      4%. It is rapid and specific for the assay of sulphacetamide in degraded
      opthalmic preparations.

PMID- 16414622
TI  - Phytopharmacological evaluation of Ficus glomerata, Roxb. fruit for hypoglycaemic
      activity in normal and diabetic rabbits.
AB  - The investigation was designed to study effects of powdered Ficus glomerata
      fruits on blood glucose levels in groups of normal and alloxan-diabetic rabbits.
      In normal groups, administration of 1, 2, 3 and 4 g/kg body weight of F.
      glomerata pulv lowered the blood glucose levels significantly. The methanolic
      extract of the drug also produced significant hypoglycaemia but the aqueous
      extract could not produce this effect. In alloxan diabetic rabbits the treatment
      with 2, 3 and 4 g/kg body weight of the plant drug produced a significant fall in
      blood glucose levels. The methanolic extract of the pulv also produced a
      significant decrease in the diabetics hut the aqueous extract could produce a
      slight fall in glucose levels in these rabbits. Acetohexamide in 500 mg/kg dose
      produced a significant decrease in blood glucose levels of the normal rabbits
      only. Therefore, it is conceivable that the indigenous plant contains more than
      one type of hypoglycaemic principles which seem to act by producing an
      organotropic effect on the B-cells resulting in an increased secretion of
      insulin. In addition, it is also possible that the drug acts by providing certain
      necessary elements to the beta cells, especially in the alloxan-diabetic rabbits.
      Furthermore, it may be assumed that the indigenous plant pulv would also help the
      diabetics by providing certain essential minerals like calcium, phosphorus, zinc,
      magnesium, manganese, copper and others.

PMID- 16414623
TI  - Spectrophotometric determination of tolmetin sodium in capsule dosage form.
AB  - Two different U.V. spectrophotometric modes, zero-order and first derivative,
      have been applied for the quantitation of tolmetin sodium (Tolectin 200 mg) in
      bulk form and in its pharmaceutical formulation. Direct U.V.-measurement of
      aqueous solution of the drug at 325 nm exhibits significant linearity at the
      concentration range 0.1-1.5 mg% with a coefficient of variation (C.V.) 0.34%. The
      first derivative (d'A) spectrophotometric measurements at 342 nm yield results
      with a C.V. 0.29%. Drug assay of the capsule gives percent contents of 100.42 +/-
      0.34 and 100.28 +/- 029 by adopting zero-order and d'A spectrophotometry
      respectively. The reproducibility and accuracy the two proposed methods have been
      assessed by employing standard additions technique. Accordingly the percent
      recoveries obtained were 99.60 +/- 0.22 and 100.16 +/- 026 for the zero order and
      the d'A-spectrophotometry respectively.

PMID- 16414625
TI  - Hypocholesterolemic effects of garlic in cholesterol fed rabbits.
AB  - Healthy male rabbits weighing about 1 Kg to 1.5 Kg were divided into 4 groups.
      Group-I fed on normal stock and 50 mg cholesterol per day. Blood cholesterol
      levels in different groups of male rabbits (controls, crude garlic treated,
      petroleum ether extract treated and ethanol extract treated) show a significant
      inhibitory effect on the rise of serum cholesterol level. Thus, it was found that
      the extracted oils which were believed to be in solvent extracts and crude garlic
      effectively prevent rise in serum cholesterol level. The crude garlic is more
      effective than petroleum ether and ethanol extracts. Ethanol was least effective
      in suppressing serum cholesterol concentration.

PMID- 16414624
TI  - Peptidic uraemic toxins.
AB  - A systematic investigation concerning uraemic toxicology has been made using
      modern analytical methods. The interest is especially focused on substances which
      are present in uraemic subjects in high concentrations, the so called "uraemic
      toxins". The samples from biological fluids have been screened with special
      regards to the presence of peptides and low molecular proteins. These peptidic
      uraemic toxins are thought to be responsible for certain physiological
      disturbances when present in uraemic subjects.

PMID- 16414626
TI  - Evaluation of antidiabetic effects of chlorpropamids in the presence of aspirin.
AB  - The present work has been done in an attempt to evaluate the hypoglycemic effect
      of Chlorpropamide in the presence of aspirin. Diabetiogenic effect of Alloxan was
      utilized which produced an Insulin-Dependent Diabetic State in the animals.
      Diabetic animals were given oral Chlorpropamide (100 mg/kg body weight) and it
      was seen that the drug reduced the blood sugar values although not to a
      significant level. Later the animals were given aspirin (30 mg/kg body weight)
      alongwith the daily dose of Chlorpropamide and a more significant reduction of
      blood sugar level took place.

PMID- 16414627
TI  - Effect of hypothermia on the twitch and tetanic contractions of denervated rat
      diaphragm muscle under isotonic conditions.
AB  - Effect of hypothermia was studied on the twitch and tetanic contractions of the
      chronically denervated rat diaphragm muscles under isotonic conditions. The
      muscles were denervated for 15-20 days and the temperature was lowered from 35
      degrees C to 15 degrees C. The results showed that hypothermia and chronic
      denervation had very little effect on the isotonic contraction parameters since
      these were found to be unaltered at all temperatures except at 15 degrees C. It
      is suggested that denervation has no significant effect on the contractile
      component of our experimental muscles.

PMID- 16414628
TI  - Mycotoxins in foods (2) oil-seeds and their products.

PMID- 16414629
TI  - Photo-oxidation of sulphanilamide to azo and azoxy compounds.
AB  - The second-order kinetics for the photochemical formation of azobenzene-4, 4
      disulphonamide has been studied at pH 1-11 and at pH 7.0 in the presence of five
      antioxidants. The rate constants are not affected by changes in pH in the region
      of 5-9 at which the molecule is predominantly in the unionised form. The rate of
      formation of azobenzene-4, 4'-disulphonamide is inhibited upto 80% by ascorbic
      acid. A scheme for the photo-oxidation of sulphanilamide to the azo and azoxy
      derivatives has been outlined.

PMID- 16414630
TI  - The derivatives of 3-(1H-benzikmidazole-2) propanoic acid synthesis and analgetic
      and anti inflammatory activity.
AB  - Several derivatives of 3-(1H-benzimidazole-2) propanoic acid (Procodazol) were
      prepared using some aldehydes by the condensation reaction. The resulting
      products were lactam and acid derivatives. According to the spectral studies it
      was found that the hydrogen atoms of the 3-methylene group of 3-(1H-benzimidazole
      2) propanoic acid take part in the reaction. 3-(2'-(Acetoxyphenyl) methylene)-2,
      3-dihydro-1H-pyrrole (1, 2a) benzimidazole lone (3c) was found to possess some
      analgetic properties.

PMID- 16414631
TI  - Interaction of succinate Ubiquinone reductase with sulphate ion.
AB  - A new type of slow change of succinate Ubiquinone reductase (EC 1.3.99), activity
      which is induced by sulphate ion is described. After preincubation of
      submitochondrial particles or succinate ubiquinone reductase with sulphate both
      preparations catalyze succinate: phenazine methosulphate reductase reaction with
      a significant lag. When added to the assay medium sulphate ion induces biphasic
      time-dependent competitive inhibition of the enzyme. The sulphate-induced
      inhibition is apparently due to a rapid interaction of the anion with an active
      site of the enzyme which is followed by a slow pH-dependent (pK = 7.2)
      transformation of the enzyme inhibitor complex. pH profiles of the overall
      succinate ubiquinone reductase reaction and of equilibrium between fast and slow
      enzyme-sulphate complexes suggest that the same protolytic equilibrium step is
      involved in the formation of an active intermediate and an inactive enzyme
      sulphate complex.

PMID- 16414632
TI  - The effect of gitalin in the sodium pump in erythrocytes of Rattus norvegicus.
AB  - The study reports of the effect of gitalin on the erythrocytes sodium pump of
      Rattus norvegicus the administration of 0.75 mg gitalin daily for seven days
      increased the average sodium content in erythrocytes. The rise in erythrocyte
      sodium content following acute gitalin therapy was proportionally more than the
      number of sodium pumps occupied by gitalin.

PMID- 16414633
TI  - Antifungal activities of the oils of Nigella sativa seeds.
AB  - Antifungal activities of the oils of N. sativa seeds were tested against twenty
      fungi including pathogenic and industrial strains. All the oils were found to
      have significant activities against the fungi, but the volatile oil showed
      stronger and wider range of antifungal activities. MIC values of the volatile oil
      was also determined against three pathogenic fungi and lowest MIC was found
      against Aspergillus fumigatus.

PMID- 16414634
TI  - Saudi folk medicine: phytochemical and antimicrobial screening.
AB  - Plants of 25 families, encompassing 30 species were selected on the basis of
      their folklore uses and literature data for the present screening. Besides
      phytochemical screening the plant extracts were prepared and tested for their
      antimicrobial activity. The result of the testing showed that about 77% of these
      plants exhibited some level of antibacterial activity. The most common chemical
      constituents found in these plants were sterols and/or triterpenes, falvonoids,
      alkaloids and tannins. Volatile oils, volatile bases, saponins, coumarins,
      anthraquinones and cardiac glycosides were also detected.

PMID- 16414635
TI  - A comparative study of the effects of ethanol, acetylcholine and adrenaline on
      various parameters of intestinal contractions of rabbit.
AB  - A comparative study was carried out to observe the effects of ethanol,
      acetylcholine and adrenaline on various parameters of the contraction cycle of
      rabbit intestine. Acetylcholine and adrenaline were used in concentrations of 10(
      3), either alone or in combination with absolute ethanol. The results showed that
      ethanol and acetylcholine had no effect on the rate of intestinal contractions
      while adrenaline increased it significantly. However, all these drugs decreased
      the active tension of the contracting intestine, the decrease being minimum for
      ethanol, moderate for acetylcholine and maximum for adrenaline. On the contrary,
      a small transient decrease in resting tension was produced by ethanol and this
      occurred at a very fast rate while adrenaline produced a marked decrease in this
      parameter, its rate being 6-10 times slower. Ethanol and acetylcholine were also
      found to increase the resting tension, it being 2 times greater and occurring at
      a faster rate with acetylcholine. It is suggested that these drugs produce their
      effect by altering resting membrane potential, Ca++ and other ion fluxes.

PMID- 16414636
TI  - Hypoglycemic effect of Allium sativum on oral glucose tolerance test in rabbits.
AB  - The effect of crude garlic and its two organic extracts on blood glucose levels
      of rabbits have been studied. It was found that the petroleum ether extract and
      crude garlic juice had some hypoglycemic effect on the induced hyperglycemia in
      the experimental animals, whereas no effect was observed on the group fed on
      ethanol extract.

PMID- 16414637
TI  - Preliminary phytochemical screening of four common plants of family
      caesalpiniaceae.
AB  - Preliminary phytochemical screening of Bauhinia variegata, Cassia fistula, Cassia
      tora and Tamarindus indica did not reveal alkaloids and unbound anthraquinones
      while glycosides as well as flavonoids were present in all the four species of
      the family caesalpiniaceae. Cardiac glycosides were absent only in C. tora and
      saponins were present only in T. indica, B. variegata and T. indica were devoid
      of bound anthraquinones while bound anthraquinones were present in C. fistula and
      C. tora. Paper chromatography revealed 6 spots in solvent system I, and 5 spots
      in solvent system 2, showing different Rf values. The per cent yield of crude
      glycosides was 3.18 in B. variegata, 4.03 in C. fistula, 4.45 in C. tora and 4.14
      in T. indica.

PMID- 16414638
TI  - Effect of Mukteswar and Komarov strains of newcastle disease vaccines on egg
      production.
AB  - Effect of live mesogenic strains of Mukteswar and Komarov ND vaccines was studied
      on the egg production of laying birds. The results showed that pullets vaccinated
      with Mukteswar ND vaccine produced more eggs than the Komarov vaccinated or non
      vaccinated birds. The peak egg production was noted at the age of 29 weeks in
      these birds and this latter decreased. When birds were re-vaccinated with the
      same vaccine and route, at the age of 32 weeks, the egg production again
      increased to 81%. Intra muscular vaccination with Komarov ND vaccine demonstrated
      11% less egg production than the birds vaccinated with Mukteswar ND vaccine. In
      all the experiments, birds were found to be severely affected by the hot weather
      resulting in a drop of egg production.

PMID- 16414639
TI  - Therapeutic and injurious characteristics of thermal and sulphurous springs.
AB  - The dissolution of underground rocks by water, flowing underneath, makes the
      water rich with chemical compounds and ions. These chemical constituents with the
      heat of water, absorbed from the exothermic reactions of volcanic activities,
      gain the therapeutic properties to human sufferings or vice versa. The general
      history of sulphurous and thermal springs, their effects and causes are discussed
      below.

PMID- 16414640
TI  - Salicylazosulfapyridine (4-pyridyl-(2)-aminosulphonyl-3-carboxy-4
      hydroxyazobenzol) in the treatment of rheumatoid arthritis.

PMID- 16414641
TI  - Studies on the mode of action of non-steroid anti-inflammatory drugs.
AB  - During the past decade the mode of action of anti-inflammatory drugs has mainly
      been related to the inhibition of prostaglandin (PGS) synthesis (Vane 1971). In a
      presentation by Burne (1982) it has been shown that PGS are not the only most
      important mediators of inflammation, and the inhibition of prostaglandin
      synthesis alone does not explain all common effects and mode of action of NSAIDs.
      Hence alternative concepts are presented in this paper, which may be adopted as
      the mode of action of NSAIDs.

PMID- 16414642
TI  - Photo-oxidation of sulphanilamide to blue product.
AB  - Aqueous solutions of sulphanilamide undergo photolysis to produce several
      compounds including the blue oxidation product. The kinetics of the reaction
      leading to blue product has been studied and the apparent first-order rate
      constants for the formation of blue product at pH 1-11 have been calculated.
      Effect of certain antioxidants on this reaction at pH 7.0 and rates of inhibition
      have been determined. Ascorbic acid has been found to completely inhibit the
      formation of blue product. A reaction pathway for the photo-oxidation of
      sulphanilamide to blue product has been suggested. The blue product has been
      shown (James, 1940) to possess much higher antibacterial activity than
      sulphanilamide.

PMID- 16414643
TI  - The influence of crude cobra venom on electrolyte levels and Na+, K+ ATPase
      activity in erythrocytes liver and heart cells.
AB  - The present study focuses on the in vitro interaction between snake venom and
      electrolytes and Na+, K+-stimulated ATPase system in number of tissues from
      humans and animals. The venom produced a change in the resting cellular sodium
      and potassium levels in all the tissues tested. When compared, only human
      cancerous tissue showed apparent fall in sodium and a rise in potassium, while no
      significant change occurred in normal. The effect of snake venom (25 microg/ml)
      on sodium pump activity, a transport enzyme, was assessed in normal tissues.
      Human erythrocyte membrane pump was significantly inhibited than-rabbit heart and
      liver tissue. With subsequent increase of dose no further change took place in
      these cells. A non significant and comparable stimulation in the enzyme activity
      was seen with rabbit heart and liver. These findings demonstrate that human
      erythrocytes are more sensitive towards the venom and secondly that venom might
      potentiate its cellular function by modifying the sodium pump activity.

PMID- 16414644
TI  - The synthesis of 4-[(2-Hydroxy-4-quinolyl)methyl]-3,5-pyrazolidinediones and
      related products.
AB  - In the present work, the synthesis of 4-[(2-Hydroxy-4-quinolyl)methyl]-3,S
      pyrazolidinediones and related compounds has been described.

PMID- 16414645
TI  - Studies on Achras sapota L; part III. Isolation and identification of some
      triterpenoids from the leaves of Achras sapota L.
AB  - The triterapenoids present in the leaves of Achras sapota L belongs mainly to
      alpha/beta-Amyrin and Lupenol series. A long straight chain hydrocarbon,
      tritriacontane was also found to be present in the n-Hexane extract of the
      leaves.

PMID- 16414646
TI  - Cathartic activity of Cassia species.
AB  - Cathartic activity of the three Cassia species i.e. Cassia angustifolia, C.
      fistula and C. holosericea has been assessed by Lou's method. Comparative study
      revealed that C. angustifolia is more active as compared to C. fistula and C.
      holosericea. Furthermore, the comparative study of their Sennoside content also
      supports the above finding, as they bear some correlation between Cathartic
      activity and Sennoside contents. The legumes of all the three species were found
      to be mere active as compared to leaves in their Cathartic activity.

PMID- 16414647
TI  - Characterization of salt tolerant bacteria isolated from the rhizosphere of
      Leptochloa fusca and Atriplex rhogodoidaes.
AB  - Bacteria from the rhizosphere of Leptochloa fusca (Lf) and Atriplex rhogodoidaes
      (Ar) were isolated at 0.5 M NaCl Plates. Apparently 20 different purified
      colonies from each plant species were picked and streaked on 0.8 M salt
      concentration. The survivors were subsequently streaked on 1 M salt
      concentration. Only 4 from Lf and 3 from Ar could manage to grow at 1 M
      concentration. Slight variation was observed in colonial morphology of these
      strains. Except for Lf-5b all strains were Gram-negative rods. U-5b was Gram
      positive and pleiomorphic. Lf-5b and Ar-5b, were non-motile, while rest of the
      isolates were motile. Catalase and oxidase enzymes were present in Lf-2a, Lf-4a
      and Ar-5b while Lf-4b was positive for oxidase only. All but Lf-2b and Ar-5b
      could ferment glucose and mannitol. Slight variation in the 20 biochemical
      characters of these isolates was observed. According to Bergey's classification
      these isolates fall in four groups. Lf-2b and Ar-Sb belong to Gram-negative
      aerobic rods; Lf-4a, Lf-4b and Ar-Sa to Gram-negative facultative anaerobic rods;
      Ar-3b to Gram-negative anaerobic rods; and Lf-Sb to Gram-positive anaerobic
      bacteria.

PMID- 16414648
TI  - Effect of triturated dilutions of ethanol on the peristaltic contractions of
      isolated rabbit intestine.
AB  - Effect of triturated dilutions of ethanol from to 10(-3) to 10(-24) were studied
      on the peristaltic contractions of isolated rabbit intestinal pieces. Triturated
      dilutions of ethanol were applied in two doses. It was generally observed that
      the addition of first dose was followed by a small increase of 1.1 gms. in the
      resting tension which occurred at a slower rate in about 36.5 sec. The second
      doses however, increased the resting tension by 24 gms, in about 21 sec. In
      addition, the active tensions showed large variations on the application of first
      doses of triturated ethanol, while the second doses always decreased this
      parameter below the first dose levels. The rate of contractions was however,
      unaltered by both the first and second doses of ethanol, although an increase in
      the contraction times was found to be balanced by a simultaneous decrease either
      in the peak duration or relaxation times. The results are discussed in terms of
      electrophysiological, active state and free ionic Ca++ release phenomena.

PMID- 16414649
TI  - Toxicity and anticoagulant activity of Salvia splendens.
AB  - Toxicological studies carried out on aqueous extract of Salvia splendens commonly
      known as Red Sage reveals that the drug is toxic only in higher doses and causes
      hemorrhages. LD50 of S. splendens is 1287.3 mg/Kg. Salvia splendens possesses
      anticoagulant property. The aqueous root extract of Salvia splendens increases
      the clotting time of dog's plasma by increasing the normal prothrombin time from
      10-15 seconds to 35 seconds. Furthermore, the anticoagulant activity depends upon
      the part of the plant i.e. flowers, aerial parts and roots.

PMID- 16414650
TI  - Cyclopeptide alkaloids: further studies on mauritine-C and sativanine-C.
AB  - The 14-membered cyclopeptide alkaloid mauritine-C and the 13-membered
      cyclopeptide alkaloid sativanine-C were isolated from Zizyphus spinea-christi and
      Zizyphus sativa commonly used in the Saudi Folklor medicine. The N-formyl
      derivatives of these compounds were prepared and their corresponding spectral
      data was analyzed. Fundamental differences were observed in the mass
      spectrometric fragmentation of the newly formed derivatives as compared to the
      parent compounds mass spectrometry was found a useful tool to substantiate the
      fragmentation pattern proposed for these potential natural products.

PMID- 16414651
TI  - Effect of temperature on the maximum rate of rise of tension in denervated rat
      diaphragm muscle.
AB  - Effects of chronic denervation and temperature were studied on the maximum rate
      of rise of tension in isometric twitch and tetanus of rat diaphragm muscles. The
      muscles were denervated for 15-20 days and the maximum rate of rise of tension
      was measured according to Hill (1951). The results showed that the maximum rate
      of rise of tension in twitch and tetanus was temperature dependent, exponentially
      increasing with increasing temperatures in both the normal and denervated
      muscles. A further observation was that the maximum rate of rise of tension in
      denervated muscle was always smaller than normal controls. It is suggested that
      probable changes in the series elasticity and duration of active state in the
      denervated muscle are responsible for the observed changes.

PMID- 16414652
TI  - Chemical investigation of the internal secretion of the sperm blue whale.
AB  - Ambergris, which is an internal secretion of the sperm blue whale, was extracted
      with 96% ethanol. The saponified and unsapondied portions have been studied in
      detail. The number of fractions and components of the unsaponified matter as
      separated by column and thin layer Chromatography confirm the presence of ambrein
      (triterpenoid) as well as same other steroid. The saponified portion is reported
      to contain stearic, oleic, linoleic, archidic and betenic acids. More than one
      compound have been found in each fraction.

PMID- 16414654
TI  - Extrachromosomal genetic elements.

PMID- 16414653
TI  - The biosynthesis of some beta-lactam antibiotics.

PMID- 16414656
TI  - Effect of solvent on UV and visible spectra of formylmethylflavin and
      photoproducts.
AB  - The UV and visible absorption maxima and the molar absorptivities of
      formylmethylflavin and its photoproducts, lumichrome and lumiflavin, have been
      determined in water (pH 7.0), acetonitrile, methanol, ethanol, 1-propanol, 1
      butanol, dichloroethane and chloroform. The effect of solvent polarity on the
      position and intensity of the absorption bands of these compounds has been
      demonstrated. The variations in the pi-pi* transitions corresponding to the main
      absorption bands of flavins are discussed.

PMID- 16414655
TI  - Antibacterial activity of clove extracts against phagogenic strains including
      clinically resistant isolates of Shigella and Vibrio cholerae.
AB  - Clove extracts (petroleum ether, chloroform and ethanol extracts) were tested in
      vitro for their antibacterial activity against forty isolates of pathogenic
      bacteria including clinically resistant (resistant to ampicillin and nalidixic
      acid) strains of twenty-five Shigella and four Vibrio cholerae. All of the
      isolates except Pseudomonas aeruginosa showed promising sensitivity to the
      extracts.

PMID- 16414657
TI  - Response of coriander to the mode of phosphorus application.
AB  - Three modes of phosphorus application, partly or fully through the soil or
      foliage, were conducted to evaluate the effect of P application mode on green and
      fruit yields of coriander and their chemical constituents. The highest values in
      plant height, green and dry matter production as well as fruit yield, were
      recorded when P was given partly through soil and foliage. Generally, the three
      methods of P application increased carbohydrate and protein concentrations in
      shoots and fruits as compared to the control, in the two seasons in both cuts.
      The addition of P partly through soil increased the volatile oils concentration
      of shoots and fruits in the two cuts in both seasons, over the all treatments.
      The identification of volatile oils in shoots and fruits varied according to the
      mode of P application.

PMID- 16414658
TI  - Synthesis of some substituted furan amino acid derivatives.
AB  - Some substituted furan amino acid derivatives were prepared from 5-bromo furoyl
      chloride and 5-nitrofuran acryloyl chloride. Some of the prepared compounds were
      found to be highly active against gram negative bacteria.

PMID- 16414659
TI  - Multicomponent spectrophotometric assay of sulphacetamide and photodegradation
      products.
AB  - A multicomponent, spectrophotometric method has been developed for the
      simultaneous determination of sulphacetamide, sulphanilamide and major
      degradation products in photolysed solutions. It is based on a three component
      (Sulphacetamide, sulphanilamide and azobenzene-4, 4'-disulphonamide) assay at pH
      4.0 using 258, 268 and 320 nm as analytical wavelengths. The blue oxidation
      product of sulphanilamide is determined independently at 550 nm. The
      reproducibility of the method judged by the analysis of synthetic mixtures, is
      within +/- 5%. The method is stability indicating for the assay of sulphacetamide
      in degraded eye-drop preparations and could also be conveniently used for
      photodegradation studies.

PMID- 16414660
TI  - Studies on growth and chemical constituents of parsley plants in relation to
      ontogenesis.
AB  - Eleven parsley plant samples were collected periodically every two weeks after 30
      days from sowing time. The collected samples were chemically analysed in order to
      determine their dietic and medicinal values. The 120 days old sample contains the
      highest percentage of essential oils. The qualitative and quantitative analysis
      of the essential oils were performed by GLC. Five cuts were taken to determine
      the growth changes and yield. The highest yield was detected in the 3rd cut (120
      days old plants).

PMID- 16414661
TI  - UV-spectrophotometric determination of alpha-tocopherol acetate in pharmaceutical
      preparations.
AB  - UV-spectrophotometric method has been developed to estimate alpha-tocopherol
      acetate in tablets and soft capsules. The lambdamax was found to be 285 nm in
      ethanol and isopropanol. The percentage error was found to be 2 to 7 in alpha
      tocopherol acetate preparations whilst this increases in multivitamin
      preparations.

PMID- 16414662
TI  - Effect of dexamethosone on babesiosis in Tatera indica (Hardwicke).
AB  - Two subcutaneous injections of 0.15 mg of dexamethasone/kg of body weight caused
      a substantial increase in Babesia microti. Parasitized RBC of Tatera indica,
      indicating that this was a useful method for revealing the presence of latent
      infections. A relative neutrophilia, lymphocytopenia, and eosinopenia were also
      seen in the long term B. microti infected carrier T. indica after 0.15 mg or 0.01
      mg of dexamethasone/kg Noninfected T. indica treated with dexamethasone had a
      neutrophilic leucocytosis and a transient lymphocytopenia. Spleen to body weight
      ratios of non-infected T indica decreased significantly (P<.02) after three
      injections with either dosage level. These ratios did not significantly (P>0.05)
      decrease in dexamethasone treated infected indica.

PMID- 16414663
TI  - Toxicity of nicotine derivatives and their effect on the protein pattern of 4th
      immature stage of red cotton stainer Dysdercus koenigii (Fabr) (Hemiptera:
      Pyrrochoridae).
AB  - Toxicity of Nicotine dust and Nicrotine cyanurate was observed against the 4th
      immature stage of Dysdercus koenigii (Fabr.) by injection method. Mortality rates
      were noted after 24 hours of treatments. LD50's were calculated as 7.2
      microg/nymph and 9 microg/nymph for nicotine dust and nicotine cyanurate
      respectively. Changes in the flow of protein metabolites occur with higher and
      lower doses of both the compounds.

PMID- 16414665
TI  - Studies on the bile acids of the gall bladder bile of a mud-puppy, Salamander
      necturus.
AB  - The major bile acids of gall bladder bile of salamander necturus have been
      reported and shown to be taurine conjugates. The bile acid conjugates were
      hydrolysed and the free bile acids were separated by thin layer chromatography
      and identified through gas liquid chromatography and mass spectrometry (GC-MS) as
      methyl esters and methyl-ester trimethyl silyl ethers. About 56.3% of the total
      bus acid was present as allocholic acid whereas 3alpha, 7alpha, l2alpha-dihydroxy
      5alpha-cholestanoic acid and cholic acid represented 30.4 and 12.3% respectively.
      Dihydroxy bile acids such as deoxycholic, allodeoxycholic and
      allochenodeoxycholic were present in less than 0.5% of the total bile acids.

PMID- 16414664
TI  - Isolation and characterization of chemical constituents of Stoechospermum
      marginatum (Dictyotales, Phaeophyta) and their antimicrobial activity.
AB  - From chloroform and methanolic extracts of Stoechospermum marginatum (C. Ag.)
      Kutz. Five saturated and four unsaturated fatty acids, three sterols, four
      diterpenes and D-mannitol were isolated. The fatty acids, analysed as methyl
      esters, were myristate, pentadecylate, palmitate, margarate and nonadecylate
      among saturated and tetradecatrienoate, pentadecenoate, hiragonate and oleate
      among unsaturated ones. The sterols were identified as cholesterol [1], 24
      methylene cholesterol [2] and 24-methyl cholesterol [3]. The diterpenoids were
      determined as 19-acetoxy-5 (R), 15, 18 (R and S)-trihydroxyapata-13, 16 (E)-diene
      [4], 5 (R), 15, 18 (R and S), l9-tetrahydraxyspata-13, 16 (E)-diene [5], 5 (R),
      18-dihydroayspata-13, 16 (E)-diene [6] and 5 (R), 16-dihydroxyspata-13, 17-diene
      [7]. All these diterpenes showed strong antibacterial activity against three gram
      +ve and six gram -ve bacteria. The crude extract was found active against three
      fungi in 10 mg/ml concentration, whereas the diterpene [5] exhibited activity
      against only one fungus.

PMID- 16414666
TI  - Effect of cutting period on the yield and chemical constituents of dill.
AB  - This study was carried out in two seasons to determine the proper time for
      cutting dill plants. Plants height, fresh and dry weights/plant, number of
      inflorescences as well as fruit yield/plant and green besides fruit yields/m2
      were recorded. The concentration of proteins, carbohydrates and essential oils as
      well as its components in herb and fruits were estimated in all collected
      samples. It appeared that cutting dill plants at 75 days front sowing (for the
      1st cut) and 45 days after the tint cut (for the 2nd cut) gave the highest herb
      and fruit yields with but quality.

PMID- 16414667
TI  - Flavone glycosides of Caralluma tuberculata N. E. Brown.
AB  - Three flavone glycosides have been hoisted from the fresh vegetative part of the
      medicinal herb Caralluma tuberculata. The chemical and spectroscopic properties
      are consistent with structures of Luteolin.4'-beta-D-glucopyranosyl-(2-->1)-alpha
      L-rhamnopyranoside [1], Kaempferol-7-O-beta-D-glycopyranosyl (2-->1)-alpha-L
      rhamnopyranoside [2], Kaempferol- 3-O-beta-D-glycopyraaosyl (6-->l)-alpha-L
      rahmnopyranouide (3).

PMID- 16414669
TI  - Influence of kinetin on growth, flowering and alkaloidal contents of Hyoscyamus
      muticus L.
AB  - Plants treated with Kinetin responded very markedly and were more bushy and
      darker in colour than the controls. The physical yield was maximum in the plants
      treated with 50 PPM followed by 100 PPM and 200 PPM. Early flowering was induced
      in treated plants than the controls and it was seen first in 50 PPM. Growth and
      flowering was not very promising in higher concentration of the Kinetin. Height
      measurement indicated that plants treated with the Kinetin were larger than
      controls throughout the observation period. This indication was prominent in 50
      PPM Kinetin treated plants followed by neat higher concentrations. Chemical assay
      has shown that the concentration of alkaloids has increased though it is not very
      appreciably as compared to the physical yield of each plant. Lower concentrations
      have better effects both on physical yield and alkaloids percentage as compared
      to the higher ones. From these observations it us assumed that the use of Kinetin
      as plant growth regulator on Hyoscyamus muticus is economical and its further
      investigations may prove more useful especially on other solanaceous plants.

PMID- 16414668
TI  - Fatty acids of Inula grantioides.
AB  - The flowers of Inula grantioides collected from the vicinity of University of
      Sindh, Jamshoro Campus, Pakistan were analysed for their fatty acid composition.
      The fatty acids were converted into methyl esters and identified by gas liquid
      chromatography-mass spectrometry as myristic, pentadecanoic, palmitic, margaric
      stearic, arachidic, behenic, tricosoic, lignoceric, hexadecanoic and heptacosoic
      acid.

PMID- 16414670
TI  - Semi-micro determination of water content for the bulk samples of
      Oxytetracycline, Tetracycline and Chlortetracycline.
AB  - The semi-micro analysis of the bulk commercial samples of Oxytetracycline,
      Tetracycline and Chlortetracycline for their water content using Karl Fischer
      reagent is described. All the samples analysed comply with the limits laid down
      in European Pharmacopoeia or United States Pharmacopoeia.

PMID- 16414671
TI  - Cardiovascular effects of Bacopa monnieri (L.) pennel extract in rabbits.
AB  - The effects of the crude ethanolic extract of whole plant of Bacopa monnieri have
      been evaluated on left ventricular contractility, heart rate and coronary flow in
      isolated rabbit hearth showed cardiac depressive activity in all parameters, like
      quinidine.

PMID- 16414672
TI  - Synthesis of some phenacyl nicotinates as potential anticholesterolemic agents.
AB  - Three anticholesterolemic agents, 2,4-dimethoxy phenacyl nicotinium bromide, 2,5
      dimethoxy-phenacyl-nicotinium bromide, and 2,3,6-tribromo 3,5-dimethoxy-phenacyl
      nicotinium bromide, were synthesized and their chemical structures were
      determined by spectroscopic method.

PMID- 16414673
TI  - Screening of Veronica anthelmintica seed and Embella ribes fruit mixed in equal
      parts against gastrointestinal nematodes.
AB  - The antinematodal activity of a mixed prescription of Veronia anthelmintica seed
      (Kali zeeri) and Embelia ribes fruit (Babrang) was evaluated in goats. The EPG
      (Egg per gram) counts were made in the faeces before and on the 3rd, 10th and
      15th days of the treatment with the powder in 0.5, 1 and 2 g/kg body weight doses
      and with the water and methanol extracts equivalent to 2 g/kg of the original
      powder. The evaluation of data on 15th day of the administration showed that 2
      g/kg of powder, its equivalent amount of methanol extract and 0.01 g/kg of
      morantel tartrate are equally effective and safe in treating natural
      gastrointestinal nematode infection of the local goats.

PMID- 16414674
TI  - In vitro testing of the leaf extracts of Lawsonia alba for antimicrobial
      properties.
AB  - Leaf extracts (chloroform, ethanol and aqueous extracts) of Lawsonia elba were
      tested in vitro for their antimicrobial activity against seventeen strains of
      pathogenic bacteria and twelve fungi including seven pathogenic strains. Each of
      the extract showed good activity against most of the strains tested. The
      sensitivity of the bacteria and fungi to the extracts was compared to that of
      ampicillin, tetracycline, co-trimoxazole and griseofulvin sensidiscs.

PMID- 16414675
TI  - AC-polarographic quantitation of tolmetin sodium.
AB  - Fundamental harmonic alternating current polarography has been described for the
      determination of tolmetin sodium and its capsules, (Tolectin-200 mg). The AC
      procedure was applied by superimposing 10 mV, rms, AC voltage on a DC ramp in the
      range -1200 to -1450 mV at a frequency of 50 Hz in acetate buffer of pH 5.0
      containing 0.001% gelatin as a maxima suppressor. A three electrode assembly
      consisting of dropping mercury electrode (dme) and two Ag/AgCl/KCl (sat.)
      electrodes was employed. Mercury flow rate was 3 mg sec(-1) under a corrected
      head pressure of 80 cm. The electrode reaction was investigated by Kalousek K1
      and K2 techniques which indicated the non-reversibility of the electrode process
      on the AC time scale. The percent result obtained by standard addition procedure
      was 101.4 +/- 2.0 for tolmetin sodium capsules.

PMID- 16414676
TI  - Biochemical building blocks of a lepidopteran insect, Schoenobius inotata.
AB  - Schoenobius inotata, a pheromone producing insect, commonly known as rice stem
      borer, was studied for its biochemical composition namely lipid, carbohydrate and
      amino acids. The studies involved the application of column, thin layer and gas
      liquid chromatography besides mass and proton magnetic resonance spectrometry.
      Amino acid analysis was performed on automatic amino acid analyser. No such
      report on this species has so far appeared.

PMID- 16414677
TI  - Spectrophotometric assay of formylmethylflavin and photoproduct-lumichrome in
      organic solvents.
AB  - A spectrophotometric method has been developed for the assay of
      formylmethylflavin and its major photoproduct, lumichrome, in organic solvents.
      Absorption measurements are made at the respective maxima of the two compounds
      and the concentrations are determined by a two-component assay. The
      reproducibility of the method lies within +/- 5 percent. The method is specific
      and can be conveniently employed for photodegradation studies of
      formylmethylfavin in organic solvents.

PMID- 16414679
TI  - Inhibition of platelet activating factor by ajmaline in platelets: in vitro and
      in vivo studies.
AB  - The in vitro and in vivo effects of ajmaline and its derivatives on platelet
      aggregation and platelet-activating factor (PAF) induced death in rabbits was
      studied. Ajmalinc and acetyl ajmaline selectively inhibited PAF-induced
      aggregation in a concentration related manner. Weak or no inhibition of
      aggregation was observed when ADP, collagen or arachidonic acid were used as
      aggregating agents. Similarly ajmaline or acetyl ajmaline also inhibited the
      lethal effects of PAF in the rabbit. PAF (8-11 microg/kg i.v.) caused sudden
      death in rabbits due to platelet aggregation and cardiac failure. Pretreatment of
      rabbits with ajmaline (50 mg/kg i.p.) protected conscious rabbits from PAF (11
      microg/kg i.v.)-induced death. Since PAF is a powerful inducer of platelet
      aggregation via stimulation of specific PAF membrane receptors, our data is
      suggestive that ajmaline (an anti-arrhythmic agent) could emerge as a new class
      of PAF antagonists.

PMID- 16414678
TI  - Phycochemical studies on Scinaia fascicularis (Bonnemaisoniales, Rhodophyta).
AB  - The sterol composition of marine red alga, Scinaia fascicularis (Bphirg.) Huisman
      has been studied and cholesta-5, 20, 24-trien-3beta-ol, 22-dehydrocholesterol,
      brassicasterol, 24-methylene cholesterol, 24-methyl cholesterol, nor 31
      cycloartanol, ergost-5-en-3,25-diol and lanostan-3beta-ol were identified through
      mass and 1H-NMR spectroscopy. All of them were present in more or less equal
      amount. The fatty acid methyl esters, analysed through GC-MS, were found to be
      methyl laurate, tridecylate, myristate, pentadecylate, palmitate, margarate,
      stearate and nonadecylate. Methyl myristate was present in largest and laurate in
      smallest quantity, no unsaturated fatty acid could be detected.

PMID- 16414680
TI  - Serum sialic acid and glycoprotein levels in some Libyan cancer patients.
AB  - Sialic acid is a common conjugate of some serum glycoproteins and glycolipids.
      Elevated levels of serum sialic acid and alterations in serum glycoproteins have
      been observed in certain types of cancer. In this study sialic acid concentration
      in the sera of patients with various types of cancer was determined. In addition
      to this, serum glycoproteins were also analysed by electrophoretic method. Our
      results indicate that serum sialic acid levels are generally raised in all types
      of cancer studied. This increase was more pronounced in case of lung,
      bronchogenic, intestinal and breast cancer. Some alterations in the serum
      glycoprotein profiles were also observed, particularly in bronchogenic and gall
      bladder cancer where an additional band in the low molecular weight region was
      present and in lung, breast and lymphoma where a band in the middle molecular
      weight region was found missing when compared with normals.

PMID- 16414681
TI  - Amino acid composition of some common seaweeds.
AB  - The nutritive evaluation of seaweed proteins on the basis of amino acid
      composition has been reported in the present communication. Seventeen of the
      common amino acids including almost all essential amino acids have been detected
      in the protein hydrolysate of eighteen species of seaweeeds. Significant
      variations were observed in amino acid composition among the different genera of
      seaweeds. Little variation was noted in total nitrogen and inorganic contents.
      The acidic amino acids were significantly higher in species of green seaweeds.

PMID- 16414682
TI  - Phycochemical examination of Padina tetrastromatica (Dictyotales, Phaeophyta).
AB  - A marine brown alga, Padina tetrastmmatica Hauck, collected from Buleji near
      Karachi, has been investigated phycochemically. Five saturated fatty acids, i.e.
      isomyristic, palmitic, margaric, stearic and arachidic, three unsaturated fatty
      acids, i.e. palmitoleic, oleic and tetradecatrienoic have been detected and
      identified by preparation of their methyl esters and GC-MS analysis. Two sterols,
      i.e. 24-methyl cholesterol [1] and 24-methylone cholesterol [2] have been
      isolated and identified by GC-MS, EI and NMR, which are being reported for the
      first time from the genus Padina.

PMID- 16414683
TI  - A study on stability of mestranol.
AB  - Mestranol, a synthetic oestrogcn, is an oral contraceptive given alongwith
      progestogens. It is light, heat and air sensitive and on uv irradiation new
      polymeric species of glucosiduronate and sulphate conjugate are formed. The new
      species fractions of mestranol are separatable over sephadex in column
      chromatography and characterized by analytical techniques employed in this
      investigation. This investigation is aimed to study formation of these species
      quantitatively for stability induced formulations.

PMID- 16414684
TI  - Toxicity and IGR effect of two new neem products against Aedes aegypti (PCSIR
      strain).
AB  - Crude extract and isolated compounds from neem, Azadirachta indica and Melia
      azedarach (Meliaceae) are being tested in various countries. The present study
      deals with the effect of two new compounds and their parent fraction from the
      fresh winter neem leaves, isolated by Siddiqui et. al., 1986. The LC50 of NFD is
      0.58 ppm, nimocinolide 0.625 ppm and isonimocinolide 0.47 ppm. Abnormal larvae,
      pupae and intermediates were also found.

PMID- 16414685
TI  - Toxicity of crude neem extracts (N-4) and (N-9) against late 2nd instar larvae of
      Musca domestica L. (PCSIR strain).
AB  - The LD50 of crude neem extract (N-4) and (N-9) was found to be 4.80% and 0.47%,
      respectively. The range of mortality was found to be increasing (at 95%
      confidence limit) with increase in concentration of solution.

PMID- 16414686
TI  - Anaplasma marginale in Lepus nigricollis (Blanford) treated with oxytetracycline.
AB  - The objective of this study was to test the efficiency and acceptability of
      oxytetracycline hydrochloride (OTC) in anaplasmosis. Five mg OTC was the only
      drug given subcutaneous twice by a week to anaplasmotized Lepus nigricollis. The
      therapeutic results were judged in relation to the parasitized erythrocytes (PE)
      present, assessment of the clinical acceptability of OTC was perfect in
      anaplasmosis (Anaplasma marginale).

PMID- 16414687
TI  - In-vitro antifungal activity of clove extracts.

PMID- 16414688
TI  - Lipid contents of marine fish: Carcharhinus melanopterus (Black Shark) and
      Lutjanus johnii (Hira).
AB  - Total lipid composition of liver oil of two marine fish Carcharhinus melanopterus
      (Black Shark) and Lutjanus johnii (Hira) was determined. The fatty acid contents
      of total liver lipids were identified through gas chromatography-mass
      spectrometry. It was found that fatty acid methyl eaten mainly consist of
      myristic, pentadecylic, palmitic, stearic acids as saturated, and palmitoleic,
      oleic, elaidic, eicosapentaenoic, docosahexaenoic, and clupanodonic acids as
      unsaturated components. Appreciable quantities of polyunsaturated fatty acids
      (PUPA) and omega-3 fatty acids were detected.

PMID- 16414689
TI  - Analysis of fatty acids from Codium iyengarii (Bryopsidophyceae).
AB  - The green seaweed Codium iyengarii Bphirg., collected from the coast of Karachi,
      has been studied for its fatty acid composition. The acids were converted into
      methyl caters and identified by GC-MS, which revealed the presence of 11
      saturated, 10 monoethenoic and 2 ethinoic acids. Palmitic acid was present in the
      highest amount, while dodecenoic acid was in largest quantity among unsaturated
      fatty acids. Malonic, heptanoic, tridecynoic, hexadecynoic, tricosenoic, and
      heptacosanoic acids arc being reported for the first time front any species of
      Codium as well as any seaweed of Pakistan.

PMID- 16414690
TI  - New bioactive compounds of plant origin.
AB  - Crude extracts of Withania somnifera (WS) and Polygonum equisetiforme (PE) as
      well as the pure compounds isolated therefrom were screened for antibacterial and
      antifungal activity against 20 bacterial and 17 fungal cultures. The crude
      extract of PE and WS inhibited the growth of T. mentagrophyte, M. canis and A.
      boydii at an MIC of 450-500 microg/ml whereas the pure compounds inhibited the
      growth at MIC of 300-350 micro/ml. Species of Corynebacterium, Bacillus,
      Streptococcus and Staphylococcus were found to be highly susceptible to both the
      crude sad the pure compounds. MIC values of both crude extracts for different
      organisms tested were found to be higher (200-350 microg/ml) than the pure
      compounds (150-170 microg/ml). The crude extract of PE did not inhibit the growth
      of Ps. aeruginosa, however, the pure compound was found to be bacteriostatic.
      Brine shrimp and BALB/c mice lethality test indicated that these extracts maybe
      toxic at high concentration.

PMID- 16414691
TI  - Studies on the fatty acids of Dictyota species from Pakistan.
AB  - An analysis of the fatty acids extracted from three brown algae Dictyota
      dichotoma (Huds.) Lamour., D. hauckiana Nizam. and D. indica Sond. is reported.
      Altogether twelve saturated and unsaturated fatty acids were identified as methyl
      esters by GC-MS, out of which pentadecylic, palmitic and margaric acids occur in
      all the three species, while others are of selective distribution. D. indica
      slightly differed in its fatty acid composition as compared to other species.

PMID- 16414692
TI  - Sterols and a glycoside from the flowers of Inula grantioides.
AB  - The flowers of Inula grantioides were analysed for their sterol composition.
      Chromatographic separation of the acetone extract of the plant material resulted
      in the isolation of beta-sitosterol, stigmasterol and beta-sitosteryl. 11
      Hentriacontene, pentariacontene and a saturated hydrocarbon, pentatriacontane,
      were also obtained for the first time from the flowers of the plant.

PMID- 16414693
TI  - Phycochemical investigations on Centroceras clavulatum (Ceramiales, Rhodophyta).
AB  - The methanolic extract of a marine red alga Centroceras clavulatum (C. Ag.)
      Mont., collected from the coast of Karachi, was studied for its fatty acid and
      sterol compositions. The analysis of fatty acid methyl esters by GC-MS revealed
      the presence of methyl laurate, tridecylate, myristate, pentadecylate, palmitate,
      margarate, nonadecylate, arachidate, behenate, tricosanoate and pentacoeanoate
      among saturated and methyl palmitoleate and heptadecylenate among unsaturated
      acids. The sterol composition divulged the presence of 22-dehydrocholeaterol,
      cholesterol, 24-methyl-cholesterol and beta-sitosterol, identified through main
      spectrometry and 1H-NMR spectroscopy.

PMID- 16414694
TI  - Inhibition of adrenaline-induced aggregation of human platelets by Pakistani
      medicinal plants.
AB  - The effects of extracts of Pakistani plants claiming medicinal value were
      observed on adrenaline-induced aggregation of human platelets according to the
      method of Born (1962). The extracts manifested significant inhibitory activity in
      doses of 0.625 mgm(-1) to 2.5 mgml(-1) in this in vitro model. The potency of the
      plant extracts in inhibiting platelet aggregation induced by adrenaline is in the
      following order: Sida pakistanica, IC50 = 0.90 mgml(-1) > Tribulus terrestris,
      IC50 = 0.97 mgml(-1) > Solanum surattense, IC50 = 1.34 mgml(-1) Tephrosia
      subtriflora, IC50 = 1.40 mgml(-1) > Glycyrrhiza glabra (butanolic extract), IC50
      = 1.66 mgml(-1) > Urtica dioica IC50 = 2.17 mgml(-1). Further studies are
      proposed to find out whether the inhibition of adrenaline-induced platelet
      aggregation is mediated through alpha-adrenoceptor blockade or suppressed
      synthesis of prostaglandin endoperoxides.

PMID- 16414695
TI  - Toxicological studies of Melia azedarach L. (flowers and berries).
AB  - Toxicological evaluation of Media azedarach Linn. was carried out in lower
      laboratory animals, i.e. rats and mice by oral and intravenous routes. Aqueous
      and alcoholic extracts were found to be non-toxic uptil a dose of 1500 mg/kg
      orally in mice and rats. When injected aqueous extract intravenously, LD50 was
      395, 580 mg/kg (flowers) and 700, 925 mg/kg (berries) respectively in mice and
      rats. It was also observed that alcoholic and aqueous extracts of Melia azedarach
      have a mild CNS sedative effect.

PMID- 16414696
TI  - Toxicology of Physalia's (Portuguese man-o' war) venom.
AB  - The venomous pelagic coelentrate Physalia species (Blue bottle) or the Portuguese
      man-o'war has recently been studied in detail due to their hazardous effects on
      community. It was observed that the venom of the animal is lethal to man and can
      also produce cutaneous stings of varying severity. Physalia species also possess
      significant cardiotoxicity to man, rats, mice and are lethal to lower animals.
      Thu effect has been attributed to the abnormality in ionic transport across
      membranes. The cutaneous pain and musculotoxic action in human produced by
      Physalia venom may be induced by one or several high molecular weight
      polypeptides. Blockage of specified neurons and neuromuscular junction besides
      alteration in end plate potential (EPP) and end plate current (EPC) was also
      attributed to high molecular weight toxic fractions. Survey of enzymatic contents
      of Physalia venom reveals the presence of a wide variety of enzymes whose
      presence and actions were similar to that of complex enzyme mixture of snake
      venom. Besides these clinical manifestations neurotoxicity cytotoxicity and other
      physiopharmacological effects were also demonstrated.

PMID- 16414697
TI  - Drug acetylation polymorphism--a review.

PMID- 16414698
TI  - Occurrence of polyhydroxy alcohols in the gall bladder bile of a mud-puppy,
      Salamander necturus.
AB  - Bile obtained from the gall bladder of Salamander necturus was investigated for
      the presence of bile alcohols by a combined technique of Thin Layer
      Chromatography (TLC), Gas Liquid Chromatography (GLC) and Gas Chromatography-Mass
      Spectrometry (GC-MS). Dried bile salts were hydrolysed with 2.5N KOH in an
      autoclave at 121 degrees C. Unsaponifiable matter was extracted with ethyl
      acetate, three times, washed with distilled water, dried with anhydrous sodium
      sulphate,evaporated to dryness and analysed for its bile alcohols. Analytical GLC
      revealed the presence of at least thirteen bile alcohols in the mixture. Two
      major bile alcohols, i.e. 5alpha-anhydrocyprinol and 5alpha-cyprinol constituted
      about 73% of the total unsaponifiable matter. Others were identified as 3alpha,
      7alpha, 12alpha,trihdroxy-5beta-delta23-homocholene,3alpha,7alpha,12alpha
      trihydroxy-5alpha-delta24-nor-27-cholestene,3alpha,7alpha,12alpha-rihydroxy
      5alpha-delta24-cholestene,5alpha-bufol and 5alpha-dermophol.

PMID- 16414699
TI  - Socially available heroin powders--their chemical compositions and reproductive
      and behavioural effects on female rats.
AB  - Morphine is one of such substances which produce very intense euphoria and a
      prolonged period of relaxation and sedation. These opioids are known to cause
      modifications in neuroendocrine system during different stages of life, ranging
      from fetal through postnatal to adult. Heroin, an opioid, is a derivative of
      morphine and its long-term use, both in males and females, is associated with
      alterations in sexual behaviour and changes in endocrine functions. In females,
      hormonal imbalance thus resulted, can lead to amenorrhea and in some cases
      infertility. In Pakistan, heroin is available mixed with different additives in a
      variety of forms. Two varieties (S1 and S2) procured from patients visiting Drug
      Rehabilitating Clinic in the Civil Hospital, Karachi, were analysed for their
      qualitative and quantitative properties.

PMID- 16414700
TI  - Evaluation of preservatives in eye-drop preparations.
AB  - A systematic study of commonly used commercial eye-drop preparations has been
      made by identification and assay of the added preservatives, i.e. benzalkonium
      chloride, parabens, phenylmercuric nitrate and thiomersal, in forty six samples.
      The commercial samples with known preservatives contain an amount, almost in
      agreement with the values stated on label. Twenty five samples with identified
      preservative (not stated on label), contain the added compound 50-150% w/v in
      excess of the recommended limits and thus may be harmful to the eyes. U.K., US.A.
      and many other countries have strict regulations regarding the use of
      preservatives in eye preparations, because of their potential toxicity. Similar
      regulations should be promulgated in Pakistan for locally manufactured products.

PMID- 16414701
TI  - Comparative effect of cimetidine and gefarnate on normal and ulcerated albino
      rats.
AB  - Antiulcerogenic efficacies of cimetidine and gefarnate were compared in the
      normal, aspirin, acetic acid and stress induced ulcerated albino rats. In
      addition, their effects on output of gastric acid, pepsin and hexosamine were
      studied in normal and experimentally ulcerated rats. Gefarnate increased the
      glucosamine. levels in normal and ulcerated rats A significant reduction in ulcer
      formation was observed with gefarnate in aspirin, acetic acid and stress induced
      ulcerous rats. Cimetidine did not reduce acid output in the presence of exogenous
      hydrochloric acid in aspirin treated rats. A decrease in glucosamine
      concentration was also observed with cimetidine in aspirin treated rats. Thus
      cimetidine did not significantly reduced ulcer formation in ulcerated rats. In
      the present study, gefarnate was found to be more effective than cimetidine
      because of its effect in normalization of mucus barrier.

PMID- 16414702
TI  - Effect of viscosity and buffer salts on the stability of sulphacetamide
      solutions.
AB  - A study of identification and rate determination of degradation products of
      sulphacetamide in aqueous solutions during UV irradiation and thermolysis at 70
      degrees , 80 degrees and 90 degrees C is made. The effect of viscosity and buffer
      salts in presence of antioxidants on the rate of hydrolysis is investigated. An
      increase in the viscosity of solution results in a decrease in the rate of
      hydrolysis. Similar viscosity effect has been observed on the photolysis of
      sulphacetamide solutions. No significant salt effect on the rate of hydrolysis of
      sulphacetamide in citrate and phosphate buffers (pH7.4) has been noticed. The
      thermodynamic parameter, E(a), deltaH, deltaS for the reaction have been
      determined.

PMID- 16414703
TI  - Biological studies of indigenous medicinal plants--I: physicochemical and
      antimicrobial screening of non-alkaloidal constituents of some solanaceous seeds.
AB  - The seeds of Atropa belladonna Datura fastuosa D. stramoniurn and Hyoscyamus
      niger were investigated for the isolation and anti-microbial activity of non
      alkaloidal constituents. The compounds were separated by column chromatography
      and spectral studies i.e. IR and UV were performed to ascertain their chemical
      nature. The anti-microbial activity of crude extracts and purified compounds was
      tested against Gram positive and Gram negative bacteria and a fungus. All the
      micro-organisms tested were markedly inhibited, however, the crude extracts as
      well as the purified compounds isolated from the seeds of A. belladonna and D.
      fastuosa showed little inhibitory activity.

PMID- 16414704
TI  - Spectrophotometric determination of natural indoles by complexing with 1,3,5
      trinitrobenzene.
AB  - A spectrophotometric method has been developed for the quantitative determination
      of some natural indoles by complexing with the electron acceptor 1,3,5
      trinitrobenzene and measuring the absorbance in the region 460-529 nm. The RSD of
      the method is 2.5%. It is simple, rapid and convenient for the routine analysis
      of indole compounds.

PMID- 16414705
TI  - Cathodic voltammetry of riboflavin at platinum and gold rotating disc electrodes.
AB  - The electroreduction of riboflavin (FMN) has been examined by cathodic rotating
      disc voltammetry in acidic and basic media at platinum and gold electrodes. It
      has proved to be diversely reducible best at gold electrode in the alkaline
      media. Rapid voltametric determination of the substance at gold electrode was
      effective and gave a mean standard deviation of 1%. Riboflavin at platinum
      electrode is cathodically active but the voltammograms do not obey the Levich
      relationship and adsorption destroys the electrode activity. The technique can be
      conveniently applied to the rapid determination of riboflavin in pure solution
      and in formulated products.

PMID- 16414706
TI  - Determination of ampicillin in human plasma by high performance liquid
      chromatography using ultraviolet detection.
AB  - A high performance liquid chromatographic method for isocratic mode of elution
      has been developed for the determination of ampicillin in human plasma. The
      method comprises injection of the plasma after protein precipitation, separation
      by reversed-phase C18 column, using heptane sulphonic acid, sodium salt
      monohydrate as an ion-pairing agent in the mobile phase which consists of pH 3.5
      phosphate buffer-methanol. The method involves UV-detection at 225 nm. This
      method provides a simple tool for the rapid analysis of ampicillin with high
      degree of accuracy and precision, where the drug level is in microgram range.

PMID- 16414707
TI  - Comparative composition of fatty acids of codium decortica tum and C. Flabellatum
      (bryopsidophyceae).
AB  - Fatty acid composition of two green seaweeds Codium decorticatum f. monstrosum
      (Montagne) Nizamuddin and C. flabellatum Silva et Nizamuddin, found in Karachi
      coastal waters, has been reported. Altogether 15 saturated and 22 unsaturated
      fatty acids including 13 monoenoic, 4 dienoic and 5 trienoic acids were
      identified as methyl esters by gas chromatography-mass spectrometry. They include
      one saturated hydroxy and three substituted unsaturated fatty acids. The 2,3
      dimethoxy propanoic, 3,8.dimethyl-2,7-nonadienoic, 7-ethyl-3-methyl-2,
      6.undecadienoic, 3,7,11-trimethyl-2, 6, 10-dodecatrienoic, nonacosatrienoic and
      nonacosanoic acids are being reported for the first time from any species of
      Codium as well as any seaweed of Pakistan. Both the seaweeds exhibited specific
      differences in their fatty acid composition.

PMID- 16414708
TI  - Identification and quantitative determination of morphine in the urine of heroin
      dependents.
AB  - Morphine in the urine of heroin addicts was identified by TLC using methanol,
      water, benzene and glacial acetic acid (80:15:15:5) and ethyl acetate, methanol
      and ammonium hydroxide (25:10:5) as solvent systems and potassium iodoplatinate
      and iodine as the developing reagents. Potassium iodate in alkaline medium gives
      a yellowish golden colour having maximum absorbance at 450 nm. By this reaction
      the minimum limit of identification and quantitative determination of morphine is
      2 microg/ml. It provides a basis for the spectrophotometric determination of
      morphine in the urine of heroin addicts.

PMID- 16414709
TI  - Chemical constituents of tagetes patula L.
AB  - The tubers of Corydalis rutifolia subsp. erdelii were analyzed for their
      alkaloidal content. Chromatographic separation of the alkaloid extract of the
      plant material resulted in the isolation of 25 isoquinoline alkaloids. Among
      these, oxosarcocapnidine and oxocularin have been isolated for the first time
      from this plant.

PMID- 16414710
TI  - Viscosity and stability stijdies of hydroxypropyl methylcellulose polymer
      solutions.
AB  - Viscosity studies of three grades of hydroxypropyl methylcellulose polymer
      solutions have been done in detail. The solutions showed pseudoplastic behaviour
      and their viscosity increased with increase in concentration of the polymer, but
      rise in temperature significantly lowered the viscosity. The effect of aging on
      solutions' viscosity at 25 degrees C was measured.

PMID- 16414711
TI  - Multicomponent spectrophotometric assay of cyanocobalamin, hydroxocobalamin and
      riboflavin.
AB  - The photolysis of cyanacobalamin to hydroxocobalamin in aqueous solution is
      influenced by riboflavin. A multicomponent spcctrophotometric method has been
      developed for the simultaneous determination of cyanocobalamin, hydroxocobalamin
      and riboflavin in degraded solutions by absorbance measurements at 550, 525 and
      445 nm. The relative standard deviation of the method is 2,5% and the recoveries
      range from 97.3-103.3%. The method has been applied to study the photolysis of
      cyanocobalamin in presence of riboflavin.

PMID- 16414712
TI  - Screening of marine algae of karachi for haemagglutinin activity.
AB  - Ethanol extracts of 66 species of marine benthic algae, collected from the
      coastal areas of Karachi, Pakistan, were tested for haemagglutination against
      human erythrocytes of blood groups A, B, AB and O. Out of 23, 16 and 27 species
      of green, brown and red seaweeds only 12,5 and 14 species respectively exhibited
      a positive test for the bioactivity of haemagglutinins i.e. the activity was
      found in half of the investigated species of Chlorophyta and Rhodophyta but only
      in one third of Phaeophyta.

PMID- 16414713
TI  - Cyclic voltammetric adsorption behaviour of riboflavin at platinum electrode.
AB  - Cyclic voltammetric technique has been used to determine the electrochemical
      adsorption behaviour of riboflavin at platinum disc electrode in acidic solution.
      The electrode loses its activity after the first cyclic curve due to coating of
      its surface with the adsorbed species. The adsorption strength of riboflavin has
      been compared with some of the strongly adsorbed materials. This technique is
      employed to determine the amount of the species adsorbed on the surface of the
      electrode as the quantity of charge consumed is proportional to the area under
      the first cycle in the voltammogram.

PMID- 16414714
TI  - A study of comparative blood absorption of vitamin b(1) from different B-complex
      preparations.
AB  - In order to judge the therapeutic efficacy of thiamine (vitamin B(1)) in B
      complex preparations, three commercial syrup preparations were analysed for
      thiamine content and their blood absorption in rabbits was compared with that of
      thiamine as a single entity. A separate experiment was performed to find the
      effect of sugar concentration on the blood absorption of thiamine. The difference
      in the quantitative values of vitamin B(1) absorbed in the single and compound
      preparations under the same conditions has been assumed as one of the criteria to
      ascertain the therapeutic efficiency of both the forms.

PMID- 16414715
TI  - Biflavone from mangifera indiga.
AB  - The phenolic extractive of the bark of Mangifera indica yielded a known biflavone
      which was characterized by spectral and chemical methods as amentoflavone. This
      is the first report for the isolation of biflavon from Mangifera indica.

PMID- 16414716
TI  - In vitro antibacterial studies of some newly synthesized phenacyl
      thiosemicarbazones.
AB  - Four different phenacyl-thiosemicarbazone compounds were studied for their
      antibacterial activity against seventeen different species/strains. Of the four
      compounds under study, O-methoxy- phenacyl-thiosemicarbazone was found to be
      highly active against almost all the cultures under study. The other compounds
      were also found to possess antibacterial spectrum, but in very high
      concentrations for some of the cultures.

PMID- 16414717
TI  - Determination of toxicity of danitol, methoprene and neem formulation against
      stored grain pest, sitophilus oryzae L.
AB  - Toxicity of a synthetic pyrethroid (Danitol 10 E.C.), methoprene (J.H.A.) and
      crude neem extract formulation (RB-b +PBO +Tx) in synergestic form was determined
      in laboratory by contact method against adults of Sitophilus oryzae. Observations
      after 24 hours of treatment showed that 50% of the adults died at 0.39 mu/cm(2)
      of Danitol, 6.28 mug/cm(2) of neem formulation and 18.85 mug/cm(2) of methoprene,
      the three products used in this experiment. Danitol was found more effective as
      compared to neem formulation and methoprene. It was found that the plant product
      formulation and a synthetic product are more effective than methoprene.

PMID- 16414718
TI  - Biochemical and electrophoretical studies of the effect of some chemosterilants
      on theenzymes of aedes aegypti (L.) larvae.
AB  - In vivo effect of standard and prospective chemosterilants on some enzymes is
      reported. Colorimetric and histochemical findings indicate that alkaline
      phosphatase is inhibited by shikonin, hempa, tepa and shikonin angelate.
      Cholinesterase is inhibited by all the compounds while diphenol oxidase is not
      inhibited. These findings have been discussed in the light of the earlier
      observations.

PMID- 16414719
TI  - DNA repair, cancer and gene therapy.
AB  - Fidelity of DNA synthesis is pivotal to our understanding of fundamental
      biological processes. An organism must replicate and repair its DNA with high
      accuracy and precision in order to maintain its genetic activity. DNA repair
      pathways enable cells to offer enhanced resistance to deleterious effects of
      chemicals and radiations (Lindahl, 1982). A number of pathways have been
      described e.g. the error-prone SOS repair (that lacks fidelity of repair
      process),the error-proof adaptive repair of alkylated DNA and inducible response
      to oxygen radical damage in DNA. These different circuits are under positive
      regulatory controls. However, the biochemical strategies employed to generate
      specific protein activators differ among the pathways. Although, the universally
      occurring repair activities seem to serve efficiently to counteract malignancy,
      error-prone polymerase and plasminogen activator have been instrumental in
      tumorigenesis, the process that proceeds by cascading of genetic errors (Sancar
      and Sancar, 1988).

PMID- 16414720
TI  - Influence of Ibuprofen on the pharmacokinetics of isoniazid.
AB  - The influence of ibuprofcn (400 mg urally) on the pharmacokinetics of isoniazid
      (500 mg orally) was evaluated in healthy human subjects (n = 30). Subjects
      participated in a two way crossover trial, the first dosing condition was
      isoniazid alone (control), and the second dosing condition was ibuprofen with
      isoniazid. The concentrations of isoniazid from the serum samples were determined
      by HPLC. The pharmacokinetic parameters show a significant (P.<0.05) increase in
      the area under the serum concentration/time curve (AUC) in both fast and slow
      acetylators of isoniazid, with a significant increase in the maximum serum
      concentration (C(max)) of isoniazid (only in slow acetylators with no effect on
      fast acetylators), a significant increase in the elimination half-life (t (1/2)),
      and the time for the maximum drug concentration (T(max)) (only in fast
      acetylators with no effect on slow acetylators).

PMID- 16414721
TI  - Spectrophotometric determination of natural and substituted indoles by complexing
      with maleic anhydr1de.
AB  - A spectrophotometric method has been developed for the quantitative determination
      of natural and ring-substituted indoles by complexing with maleic anhydride. The
      coloured complex exhibits absorbance maxima in the region 490-530 nm. The RSD of
      the method is 2.6%. The method is specific and simple and thus ideal for the
      routine analysis of indole compounds by absorbance measurements in the visible
      region. The analysis of each indole complex can be carried out within 15 minutes.

PMID- 16414722
TI  - Studies of the effect of anions (chloride, sulphate, nitrate, oxalate and
      acetate) on the pharmacological properties ofcobalt (ii) complexes with
      dithiooxamide-derived antibacterial agents.
AB  - A number of cobalt (II) complexes with dithiooramide derived antibacterial agents
      having different anions i.e., chloride, sulphate, nitrate, oxalate and acetate
      have been synthesised, and the effect of anions on antibacterial properties of
      these complexes against bacterial species Staphylococcus aureus, Streptococcus
      pneumoniae and Escherichia coli has been determined.

PMID- 16414723
TI  - Stabiliiy of cyanocobalamin solutions insunlight and artificial light.
AB  - A comparison of the degradation of cyanocobalamin (vitamin B(12)) solutions on
      exposure to sunlight and artificial light has been made using two concentrations,
      i.e. 950 mug/ml (corresponding to parenteral solutions) and 95 mu/ml (1:10
      dilution) at pH 4.0, 5.5 and 7.0. Cyanocobalamin and the photoproduct,
      hydroxocobalamin (vitamin B(12b)), have been determined by a two component
      spectrophotometric method at 550 and 525 nm. Cyanocobalamin loss (950 mug/ml and
      95 mug/ml) on exposure to sunlight for 2 hours amounts to 14.7-21.0% and 56.3
      81.5% respectively indicating that light intensity is the rate determining factor
      in the reaction. In artificial light for 2 hours B(12) (950 mug/ml and 95 mug/ml)
      loses 2.7.19.4% and 1.5-27.7% respectively. Thus B(12) degradation in sunlight is
      greater compared to that of the artificial light, with the formation of some
      oxidation products, in addition to B(12b).

PMID- 16414724
TI  - HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC ASSAY FOR THEDETERMINATION OF
      PARACETAMOL, PSEUDOEPHEDRINE HCl ANDTRIPROLIDINE HCI IN PHARMACEUTICAL
      PREPARATIONS.
AB  - The knowledge of UV absorption characteristics of paracetatmol, pseudoephedrine
      HCl and triprolidine HCl has been used to determine these compounds by HPLC
      method in pharmaceutical preparations. The method involves reverse phase
      chromatography with isocratic mode of elusion. Rather selecting a compromised
      wavelength for all the three components, "wavelength switching" programme has
      been executed to give reasonable UV responses because of the widely different UV
      characteristics of these components. This method performs well in term of the
      precision and accuracy as indicated by linear regression analysis. The RSD of the
      method is 1.12 to 2.87% and the recovery is 103.10-95.56%.

PMID- 16414725
TI  - Stability of aminophylline.
AB  - The stability of aminophyline was studied in the presence of four tablet
      excipients (callu1ose starh, glucose and lactose) and nine intravenous fluids
      (water for injection, dextrose. 10% normal saline, dextrose normal saline 5%,
      Ringer lactate, Ringer, aminoplasmal 5%, lipofundin 10%, total parenteral
      nutrition solution TPNS). Ten percent mixtures of the powder drug with the
      excipients were kept at 5 degrees C, room temperature (27+/-3 degrees C), 45
      degrees C and in direct sunlight for 30 days. The degradation of the drug
      increases with increase in temperature and on exposure to sunlight. The
      degradation is particularly intense in the presence of glucose and lactose and
      change in colour from white to yellow occurs in such mixtures. At 45 degrees C
      and in sunlight both pure drug and its mixtures change colour during the storage
      period. In intravenous fluids, the drug (1 g/L) is stable and physically
      compatible for 2 days at 5 degrees C, 27+/-3 degrees C and 45 degrees C except in
      lipofundin 10% and TPNS where the drug is stable for only 12 hours at 45 degrees
      C. Yellow tinge appears in the admixtures containing dextrose after 2 days at
      room temperature and at 45 degrees C.

PMID- 16414726
TI  - Antibacterial activity and Fatty Acid composition of the extract from hypnea
      musciformis (gigartinales, rhodophyta).
AB  - The red alga Hypnea musciformis (Wulf.) Lamour., collected from the coast of
      Karachi, Pakistan has been studied for its fatty acid composition. Sixteen fatty
      acids were found in its methanolic extract, which were analysed as methyl esters
      by GC-MS. Altogether 7 satuated, 3 monoenoic, 2 dienoic and 4 trienoic fatty
      acids could be detected. Two saturated i.e. nonadecylic and heneicosanoic acids
      and all the 9 unsaturated acids are being reported for the first time from this
      seaweed. Pentadecylate was present in largest and monadecylate in smallest
      quantity among saturated, while decatrienoate was detected in largest and
      myristoleate in smallest amount among unsaturated acids. The methanolic extract
      of the seaweed exhibited strong antibacterial activity against the gram positive
      and seven gram negative bacteria, the former appeared to be more sensitive than
      the latter.

PMID- 16414727
TI  - Stability of cyanocobalamin in parenteral preparations.
AB  - The stability of seven commercial parenteral preparations of cyanocobalamin
      (vitamin B(12)) on storage under normal laboratory conditions for a period of
      twelve months has been studied using a two component spectrophotometric method
      for the simultaneous determination of cyanocobalamin and the degradation product,
      hydroxocobalamin, at 550 and 525 nm. The single ingredient vitamin B(12)
      preparations have been found to be stable and the potency lies within the B.P.
      limits. In multi-ingredient (B(1) + B(6) + B(12)) preparations cyanocobalamin is
      unstable and degrades from 28% to 37% with concomitant formation of
      hydroxocobalamin (1.7% to 25.5%) and oxidation products amounting to 56.4% +/-
      9.3. Thus more than half of the vitamin content is lost during storage and these
      preparations are not suitable for parenteral use.

PMID- 16414728
TI  - An antitumor cardenolide with inhibitory activity against pseudomonas
      pseudomallei.
AB  - The antibacterial activity of a new cardenolide, 7beta, 14beta - dihydroxy-5-card
      20(22) enolide has been studied and it has been found to be active against
      Pseudomonas pseudomallei. The new cardenolide also exhibited antitumor activity
      in a potato disc assay.

PMID- 16414729
TI  - Effect of rifampicin on the enterohepatic recycling of estrogen in female
      tuberculous patients.
AB  - Enterohepatic recycling of estrogen after oral administration of 1 mg non
      radioactive estriol was studied in ten women taking rifampicin as one of the
      antitubercular drugs and in fourteen healthy women selected as control subjects.
      The extent of enterohepatic recycling of estriol (E(3)) during early follicular
      phase of menstrual cycle was assessed by monitoring for 48 hours the urinary
      excretion of its two major metabolites i.e., estriol-16alpha-glucuronide (E(3)
      16alpha-G) and estriol-3-glucuronide (E(3)-3-G). Of these metabolites the former
      is synthesized in liver as well as in the gut where as later is synthesized
      exclusively in the gut, hence the change in urinary level of H(3)-3-G with
      respect to E(3)-16alpha-G was considered to reflect the extent of enterohepatic
      recycling of E(3). The levels of both metabolites in urine were determined by
      radioimmunoassay. Lower values of variables including E(3)-3-G output, E(3)-3-G
      output as % of the total (E(3)-16alpha-G + E(3)-3-G) excretion and total E(3)
      (E(3)-16alpha-G + E(3)-3-G) output as % dose and the diurnal variation in urinary
      excretion of these metabolites show that the final elimination of E(3) from the
      body was quicker in these patients as compared with the control subjects,
      probably due to the reduced extent of enterohepatic recycling of E(3) as a result
      of long term chemotherapy with rifampicin.

PMID- 16414730
TI  - Changes in serum components induced by venoms of marine animals.
AB  - Serum enzyme and chemical component levels were investigated in a rat model after
      experimental envenomation by venoms of coelentrate, Physalia species, four sea
      snakes, Hydrophis spiralis, H. Cyanocinctus, H. Lapemoides and Lapemis curtus and
      a gastropod molluse Conus coronatus. The LD(50)s through i.v. route were found to
      be 4.2 mg/kg for Physalia, 0.4 mg/kg for H.spiralis 0.60 mg/kg for
      H.cyanocinctus, 0.60 mg/kg for H. lapemoides, 0.70 mg/kg for L.curtus and 2.9
      mg/kg for C.coronatus. Marked elevation of serum enzyme levels was induced by sea
      snake and Physalia venom while C.coronatus venom showed no significant change in
      serum levels. The results also indicate gross morphological changes in liver,
      spleen, gall bladder, lungs and heart by Physalia and sea snake venoms.

PMID- 16414731
TI  - Serotonergic neurotransmission in the regulation of appetite: a receptor
      approach.
AB  - Neurochemical research on brain 5-hydroxytryptamine (5-HT; serotonin) and feeding
      shows that rat brain serotonin metabolism is increased following ingestion of a
      carbohydrate rich diet to generate a neurochemical signal for the termination of
      meal. Increased metabolism may not necessarily enhance postsynaptic function;
      neuropharmacological studies therefore gained attention. Drugs which mimick 5-HT
      function at the post synaptic sites have been shown to decrease feeding in
      experimental animals. Moreover some 5-HTergic drugs are potent anorectic agents.
      Multiple receptors for 5-HT exist in the central nervous system. Drugs with
      selectivity towards 5-HT-1B/ 5-HT-1C sites produced hypophagia, while 5-HT-1A
      selective drugs increased food intake. Studies designed to investigate
      sensitivity of these receptors following starvation or satiety may prove useful
      to develop drugs for therapeutic purposes.

PMID- 16414732
TI  - Biosynthesis of car1ssol and carissic Acid.
AB  - Carissa carandas belongs to family apocynaceae which consists of 300 genera and
      1000 species. It is a large shrub with simple thorn and commonly cultivated
      throughout Pakistan for hedges and is called "Kakronda". The different parts of
      this plant have been used for various systems of medicine (Kirtikar et al.,
      1993). Cardiotonic activity was found in root of this plant (Rastogi et al.,
      1966; Rastogi et al., 1967; Vohra et al., 1963). This plant has been mentioned in
      the old chemical literature as purgative, stomachic, antihelmintics and antidote
      for snake-bite (Kirtikar., 1933). The physical characteristics of oil from the
      fruits of Carissa carandas were determined by using standard methods. In addition
      to this a study of sugars and amino acids from the fruits of this plant was also
      undertaken by the present authors (Naim et al., 1986). Our studies in the
      chemical investigation on this plant had led to the isolation of two new
      triterpene carissol Ia (Naim et al., 1985) and carissic acid lb (Naim et al.,
      1988).

PMID- 16414733
TI  - A study of the photostability of ergocalciferol (vitamin d(2)) in organic
      solvents.
AB  - The photolysis of ergocalciferol (vitamin D(2)) in several organic solvents has
      been studied to determine the influence of solvent dielectric constant and
      viscosity on the rate of reaction. Ergocalciferol degrades by zero-order kinetics
      and the rate constants vary from 0.74x10(-5) mol 1(-1) (methanol) to 1.56x10(-5)
      mol 1(-1) (chloroform). The rates appear to be a linear function of the
      reciprocal of dielectric constant and viscosity of the medium in the range
      studied.

PMID- 16414735
TI  - Lipid components of caralluma edulis (edgew.) hook.
AB  - Eighteen fatty acids (A-R), four hydrocarbons (S-V) and sterol (W) have been
      isolated from the ethyl acetate fraction of the vegetative part of the medicinal
      herb Carallurna edulis. Chemical and spectroscopic methods were used for the
      characterization of compounds as fatty acids, hydrocarbons and sterol.

PMID- 16414734
TI  - Effect of short term immobilization on mechanical characteristics of skeletal
      muscle in uromastix.
AB  - Gastrocnemius muscles of Uromastix were used to observe the effects of short term
      (7 days) immobilization in flexed position. Results demonstrated significantly (P
      < 0.01) lesser magnitude as well as rate of rise in isometric twitch and tetanic
      tensions with insignificantly different twitch/tetanus ratio in the immobilized
      muscles. Both the twitch and tetanus also demonstrated significantly (P<0.01)
      higher twitch half relaxation and twitch/tetanus half relaxation time ratio.
      While, immobilized muscles showed insignificantly higher twitch contraction,
      tetanus half relaxation and duration of active state as well as peak twitch
      duration, than control ones. These changes in the mechanical contraction
      parameters were not found to be associated with changes in weight, resting,
      stretched and shortened length of the immobilized muscles. A comparison of
      present results with previous work performed on skeletal muscles of Uromastix at
      longer period (20 days) of immobilization has suggested that Uromastix muscles
      are no prone to a significant immobilization atrophy. However, decreased
      mechanical response after immobilization irrespective of the period of
      immobilization in Uromastix muscles is probably due to a depletion in various
      substrates involved in muscle mechanics.

PMID- 16414736
TI  - Screening of some Turkish medicinal plants for their analgesic activity.
AB  - Nine crude extracts of various parts of eight medicinal plants from different
      regions of Turkey were evaluated for their analgesic activities by tail flick
      method in mice. The analgesic activities of these extracts were compared with
      acetylsalicylic acid (300 mg/kg) which is used as a standard drug. Extracts were
      given orally in doses of 300, 500 and 1000 mg/kg. 0.9% saline was also
      administered in control group of animals. Results showed that four extracts were
      having highly significant analgesic activity at all the three doses tested. Three
      showed significant effects at higher doses while two extracts did not show any
      significant results.

PMID- 16414737
TI  - Stability of paracetamol in packaged tablet formulations.
AB  - A study of the influence of various temperature and humidity conditions on the
      stability of a number of commercial paracetamol tablet formulations in original
      packaging has been conducted over a period of six months. Paracetamol degradation
      in tablets follows apparent first-order kinetics and the shelf-lives (t(90))
      range from 9.8 to 23.0 months. PVC/PVDC/Al foil and polycoated paper packaging
      offer better protection to the tablets compared to that of viscose film.

PMID- 16414738
TI  - Studies on griseofulvin: part-ii effects on the liver and kidney of albino rat.
AB  - Studies were performed on albino rats to investigate any untoward effects of
      griseofulvin on their liver and kidneys. Animals weighing between 200-250g were
      selected and divided into control and test groups. Griseofulvin was administered
      to the test groups at a dose level of 20 mg/Kg/day for 2, 46 and 8 weeks
      respectively. Animals wee sacrificed at the end of their respective study periods
      for collection of blood and removal of the liver and kidneys. Histopathological
      examination of the liver and kidneys of the treated animals at the end of 4 and 8
      weeks of griseofulvin administration showed no cytotoxic changes. It was,
      therefore, concluded that griseofulvin has no hepatotoxic effects in albino rats
      at a dose level of 20 mg/Kg/day.

PMID- 16414739
TI  - Synthesis of alkyl catechols and evaluation of their antibacterial and cyfotoxic
      activity.
AB  - A series of potential biologically active mono-, di- and tetra- alkyl catechols
      were prepared through Friedel- Crafts alkylation of catechol, and evaluated for
      their antibacterial and cytotoxic activity. The mono-substituted alkyl
      derivatives showed maximum antibacterial activity in vitro which increased with
      the increasing length of the alkyl chains. Primary screening results indicated
      that all the monoalkyl derivatives except 4- (2-octyl) catechol inhibited the
      growth of B. bronchoseptica and maximum zones of inhibition were observed in case
      of monohexyl catechols (both n- and 2-hexyl) and monobenzyl derivative. In case
      of Gram-negative organisms growth of Kl. pneumoniae and A. calcoaceticus was
      inhibited by several derivatives. Mono-3-octyl-, monononyl- and monobenzyl
      catechols markedly inhibited the growth of Kl. pneumoniae. Mono-2-heptyl catechol
      inhibited the growth of six Gram-negative bacteria. Minimum inhibitory
      concentration of six most active compounds of the series was determined against
      Gram-positive and Gram-negative organisms; it ranged from < 100 mug/ml to l0
      mug/ml. The antibacterial activity of catechol was not significant. Cytotoxicity
      test done by brine shrimp assays showed that the order of cytotoxicity decreases
      in going from mono- to tetra- alkyl catechols, and among the mono- alkyl
      products, a decrease in order of cytotoxicity was noted in going from mono-methyl
      catechol (LD(50) = 59) to monopentyl catechol (LD(50) = 173) after which the
      order of cytotoxicity gradually increased upto the largest alkyl substituent
      tested i.e. monononyl catechol (LD(50) = 114). Methyl and ethyl catechol, which
      were almost inactive in respect of their antibacterial activity possessed
      prononounced cytotoxicity as compared to higher homologues. Catechol itself did
      not show significant cytotoxicity (LD(50) = 393.27).

PMID- 16414740
TI  - Two triterpenoidal saponins from sapindus, mukorossi gaertn.
AB  - The two triterpenoidal saponins 2 and 3 containing hederagenin aglycone moiety
      (1) have been isolated from the butanol soluble fraction of the fruits (without
      shells) of Sapindus mukorossi Gaertn. Their structures were elucidated with the
      aid of chemical and spectroscopic means.

PMID- 16414741
TI  - Communication : A SIMPLE METHOD FOR THE DETERMINATIONOF CHLORPROMAZINE IN
      PHARMACEUTICALPREPARATIONS AND BLOOD SERUM.
AB  - A simple rapid and accurate method is described for the analysis of
      chlorpromazine. The method utilises reverse phase HPLC with a methanol: water
      system 50:50 as mobile phase and UV detection. The same has been successfully
      applied on locally available pharmaceutical preparations and in blood serum after
      drug administration.

PMID- 16414742
TI  - Effect of temperature and humidity on the disintegration time of packaged
      paracetamol tablet formulations.
AB  - A study of the effect of various temperature and humidity conditions on the
      disintegration time of different brands of packaged paracetamol tablet
      formulations has been made over a period of six months. Under all the storage
      conditions paracetamol tablets show an increase in disintegration time ranging
      from 9.1 to 65.5% (200 mg tablets) and 1.2 to 150.0% (500 mg tablets) on
      increasing the temperature from 25 to 45 degrees C (75% RH). The increase in
      disintegration time on increasing the temperature from 25 to 45 degrees C (100%
      RH) ranges from 14.3 to 157.7% (200 mg tablets) and 15.3 to 92.3% (500 mg
      tablets). The overall increase in disintegration time from 25-45 degrees C at 75%
      and 100% RH is 36.4 to 564% (200 mg tablets) and 10.0 to 140.5% (500 mg tablets)
      and 101.3 to 122.9% (200 mg tablets) and 2.6 to 46.8% (500 mg tablets)
      respectively. These results indicate that PVC/PVDC/Al foil packaging cause
      relatively less change in disintegration time of the tablets compared to that of
      the polycoated paper and viscose film.

PMID- 16414743
TI  - SAFETY EVALUATION OF ICTERENE - A HERBAL MEDICINE (III. Histopathological
      consideration).
AB  - In earlier studies (Zafar et al., 1993; Ahmed at al. 1993) on safety evaluation
      of Iceterne, it has been observed that the drug doesn't cause any side effect as
      far as biochemical and hematological parameters are concerned. Present study is
      an extension in the same direction through histopathologic approach.

PMID- 16414744
TI  - Isolation and biological properties of scorpionvenom proteins: iv-comparative
      study on four proteinases isolated from the venom of isometrus vittatus.
AB  - 1) Four proteinases were isolated from the venom of a local scorpion species
      Isonietrus vittatus collected from Sindh region, Pakistan and named PRO,(IA)
      PRO,(IB) PRO(IVA) and PRO(IVB). 2) Successive chromatography on Sephadex G-50, CM
      Cellulose and Sephadex G-100 yield 25.5 mg, 20.5 mg, 24.0 mg and 20.0 mg of
      PRO,(IA) PRO(IB), PRO,(IVA) and PRO(IVB) respectively. 3) The purified toxins
      were homogenous by gel filtration chromatography and SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE) giving single peak and band with an apparent molecular
      weight of 80.0 kda, 75.5 kda, 19.0 kda and 17.0 kda by gel filtration and 81.0
      kda, 74.7 kda, 18.25 kda and 17.2 kda by SDS-PAGE. 4) PRO,(IA) PRO,(IVA) and
      PRO(IVB) have LD(50s) of 1.27 mg/kg, 1.91 mg/kg, 1.68 and 1.70 mg/kg
      respectively. The former two also caused marked alteration of serum enzyme and
      chemical constituent levels at sublethal dose whereas PRO(IVA) and PRO(IVB) were
      found to be less effective. 5) Enzymatic and biological activities of all four
      were inhibited by heating at 62 degrees C. Both activities were also inhibited by
      1.8 mM EDTA and 1.2mM PMSF. Activities were enhanced by Ca(2+) but retarded and
      inhibited by Cu(4+) and Mg(2+), respectively.

PMID- 16414745
TI  - Chemical constituents of sapindus mukorossi gaertn. (Sapindaceae).
AB  - Six new fatty esters of tetracyclic triterpenoid (1-6) together with a known
      acyclic sesquiterpenoidal glycoside (7) have been isolated from the fruits of
      Sapindus mukorossi belonging to the family Sapindaceae. Their structures were
      elucidated with the help of extensive spectroscopic techniques and by chemical
      means.

PMID- 16414746
TI  - Determination of astemizole by a spectrophotometric charge- transfer method.
AB  - Iodine-astemizole charge-transfer complex has been utilized for the assay of
      astemizole. The complex formed in the proposed method shows strong absorption at
      360 nm with a corresponding molar absorptivity. epsilon of 3.26 x 10 L mol1 cm-1
      and obeyance of Beer's law over the concentration range 2-12 pg/mi. When the
      proposed method was applied to commercial tablets labeled to contain 10 mg of
      active ingredient per tablet, the mean percentage found was 99.72 +/- 1.36.
      Analysis of variance, (ANO VA), and added recovery experiments indicated adequate
      precision and accuracy for the method.

PMID- 16414747
TI  - Anodic voltammetry of norgaman at rotating disc platinum and gold electrodes.
AB  - Norgaman has been examined by anodic rotating disc electrode voltammetry in
      buffered media over the range of pH from 0-11.5. The best medium is 0.1 mol 1(-1)
      sulphuric acid in which the anodic wave is well defined at lower rotation speeds.
      The compound does not show obedience to the Levich relationship at platinum and
      gold electrodes. Rapid determination of the compound is not possible due to the
      adsorption of the oxidation product. Electrode mechanism for the reaction has
      been elucidated.

PMID- 16414748
TI  - Comparative studies on the composition of two indigenously produced varieties of
      jaman (eugenia jambolana) fruits.
AB  - Eugenia Jambolana (Syzigium Cumini) locally known as Jaman, is being used in the
      indigenous Medicinal system for treatments of various ailments including some
      related to nutrition. No study appears to have been made previously regarding the
      composition of these native varieties produced in Northern Pakistan. Two
      varieties of fruits have been analyzed for physico chemical characteristics and
      their values compared. The findings indicate that both varieties contain adequate
      amount of nutrients and minerals; in general, variety I being richer in the
      former and II in the latter.

PMID- 16414749
TI  - Isolation, identification and sensitivity pattern of microorganisms isolated from
      the urine of pregnant women.
AB  - The present studies were conducted to detect and identify the microorganism from
      the urine of pregnant women having urinary tract infection. The antibiotic
      susceptibility of these isolated microorganisms was also determined. The
      microorganisms found responsible for the infection were bacteria, fungi, yeast
      and protozoa. Among the bacteria two were identified as Gram-positive cocci i.e.
      Staphylococcus aureus and S. epidermidis, the remaining two were Gram-negative
      bacilli which were Escherichia coil and Pseudomonas aeruginosa. The fungus was
      identified as AspelEillus niger and the yeast like fungus Candida albican. The
      only protozoan found in some of the urine samples was Trichomonas vaginalis.
      These isolated and identified microorganisms were more susceptible to
      Norfloxacin, Velosef, Minocin, Nitrofurantoin, Malidixic acid and Metronidazole
      whereas antibiotics Penbritin and Cefaloridine were least effective against these
      microorganisms.

PMID- 16414750
TI  - Sterol and Fatty Acid compositions of a marine alga bryopsis pennata
      (bryopsidophyceae, chlorophyta).
AB  - The green alga Bryopsis pennata Lamouroux, collected from the coast of Karachi,
      has been investigated for its sterol and fatty acid compositions. Four sterols
      and 19 fatty acids have been isolated from methanolic extract of this alga and
      identified by (1)H-NMR, El- & GC-MS techniques. The sterol having cholesta
      skeleton was found as major constituent (78.12%), while other three with ergosta
      skeleton occurred in traces (5-9%). Seven saturated fatty acids were present in
      greater quantity (72.58%) than 12 unsaturated ones (27.41%). The latter included
      7 monoenoic, 2 dicnoic, 2 trienoic and 1 pentaenoic adds. Tricosanoic acid was
      found in the highest amount (30.24%), cyclopentenyl undecanoic and
      heneicosapentaenoic acids were the unique and rare fatty acids detected.

PMID- 16414751
TI  - Studies on marine algae for haemagglutinic activity.
AB  - Lectins (agglutinins) are important in medical and immunological applications.
      Phytohaemagglutinins have been found useful in blood banking. Keeping in view of
      these facts, the marine algae found at Karachi coastal region have been screened
      for agglutinic activity by using human erythrocytes of A, B, AB and 0 group.
      Altogether 53 algal samples were collected and subjected to extraction,
      fractionation serial dilution and titre determinations. The total marine algae
      screened for haemagglutinic activity were 44 out of these 14, 13 and 17 belonged
      to Chlorophyta, Phaeophyta, and Rhodophyta respectively. Among these three groups
      the Rhodophyta showed the highest number of lytic activity. The green marine alga
      Valoniopsis pachynema showed a titre value between 2(2) and 2(3), which is
      statistically significant. In case of brown marine algae Colpomenia sinuosa was
      found to be active (titre 2(3)), while Dictyota dichotoma, D. indica and
      Iyengaria stellata, furnished week titre value as 2(2). The red marine algae
      screened were 17, out of these 4 spp. showed significant activity (titre 2(3)),
      and these are Gelidium usmanghani, Gracilaria foliifera Hypnea pannosa and Hynea
      valentiae. While Scinaia fascicularis, Scinaia indica and Champia parvula were
      found to be weak in their onset on human erythrocytes. The results obtained were
      quite in agreement with those reported in the literature.

PMID- 16414752
TI  - Amino Acid analysis of intellan, a herbal product used in enhancing brain
      function.
AB  - Analysis of the drug "INTELLAN" and two reputed plants i.e. Centella asiatica and
      Herpestis monniera used in the preparation of the drug reveals that glutamic and
      aspartic acids are present in high concentration in the drug and are also
      required by brain in high concentration to keep itself in higher gears. Both
      these amino acids are used as neurotransmitters and also in stabilizing and
      stimulating the activities of brain, thus resulting in better performance.

PMID- 16414753
TI  - Biochemical alterations during swimming induced stress.
AB  - Stress can be defined as any stimulus that creates an imbalance in the internal
      environment. Hypothalamus has sensors that detect changes produced in the body.
      Stress can cause diseases by altering immune system, cardiovascular System
      neurotransmitter and neuroendocrine functions. Present study is designed to
      evaluate the effect of stress on few biochemical parameters during swimming
      induced stress. Significant changes have been observed especially in lipid
      profile. Corticosterone was also evaluated as reliable stress marker.

PMID- 16414754
TI  - Estimation of nor-adrenaline content of human penile tissue in diabeticmen
      with/without neuropathy.
AB  - Penile tissue consisting of corps cavernosum (cc) and tunica albuginea (TA) was
      obtained from 35 impotent patients undergoing surgery for implantation of penile
      prostheses and was examined for nor adrenaline content. 10 patients were
      classified as a non diabetic non neuropathic group, on the basis of their
      clinical history and differential diagnostic symptoms which included Peyronie's
      disease, vascular disease, hypertension and psychogenic impotence. The nor
      adrenaline content was found to be significantly lower in tunica albuginea than
      the corpus cavernosum (P<0.02) in this group. The nor adrenaline content of
      corpus cavernosum from insulin dependent (IDDM) and non insulin dependent (NIDDM)
      diabetic neuropathic patients was also found to be significantly lower (P <0.02)
      than that of non diabetic non neuropathic patients. The nor adrenaline content of
      tunica albuginea however, was similar in both groups. A non significant
      association in the content of nor adrenaline in corpus cavernosum and tunica
      albuginea among IDDM and NIDDM diabetic neuropathics was also observed. These
      results provide evidence that an underlying neuropathic factor itself causes
      vascular as well as metabolic changes in the adrenergic nerves of the penis in
      diabetics due to neuropathy in addition to the effect of the disease and thus may
      contribute to the development of impotence in these patients irrespective of
      their type of diabetes.

PMID- 16414755
TI  - Effect of cobalt (ii), copper (ii), nickel (ii) and zinc(ii) metal ions on the
      biological activity of triazine derived ligand.
AB  - A new Schiff-base triazine-derived ligand and its cobalt (II), copper (II),
      nickel (II) and zinc (II) metal complexes have been synthesised and characterised
      on the basis of elemental analysis, molar conductance, infrared, HNMR and
      electronic spectral, and magnetic susceptibility data. In order to asssess the
      effect of metal ions on the antibacterial activity, the ligand and its complexes
      have been screened against bacterial species Escherichia coli, Pseudomonas
      aeruginosa and Staphylococcus aureus. In all cases the activity/potency has
      substantially increased on complexation against one or more bacterial species.

PMID- 16414756
TI  - Haemolytic assay for the detection of adenylate cyclase toxin of Bordetella
      pertussis.
AB  - The aim of this study was to device a simple, sensitive and convenient assay for
      the detection of toxicity of the Adenylate cyclase toxin (ACT), a newly
      recognized toxin of Bordetella pertussis. Haemolytic activity of ACT was analysed
      as an assay and sheep RBCs were found to be suitable to detect the toxic effect
      down to the dose of 6.25 nmol cAMP/min/ml enzymic activity applied. The
      haemolytic activity was found to be dose-dependent.

PMID- 16414757
TI  - Stability of phosphoinosit1des containing liposomes: effects of triton x-100,
      temperature and 68 rpm.
AB  - The stability of phosphoinositide containing liposomes was investigated. It was
      found that 2% of triton X-100 completely released entrapped carboxyfluorescein.
      The release of carboxyfluorescein occurred the most of 58 degrees C (78% at 2
      hours) and the least at 4 degrees C (5.4% at 118 hours). When stored at 68 RPM
      (at 25 degrees C) about the 20% carboxyfluorescein was released at 48 hours, but
      when the liposomes were kept at 25 degrees C for the same period of time, the
      release was about 10%.

PMID- 16414758
TI  - Effect of temperature and humidity on hardness and friability of packaged
      paracetamol tablet formulations.
AB  - The influence of various temperature and relative humidity conditions on changes
      in hardness and friability of five commercial brands of packaged paracetamol
      tablets stored over a period of six months has been investigated. At 75% RH all
      sample show deterioration in hardness at 25 degrees (5-10%) and at 45 degrees (10
      39%). At 100% RH there is a little difference in deterioration in hardness at 25
      degrees (16-24%) and 45 masculine (20-28%) suggesting that once the critical
      moisture content is reached by the tablets, further increase in relative humidity
      has little effect on changes in hardness. Under the same conditions, all tablets
      show an increase in friability ranging from 2.83 to 8.02%. The overall increase
      in friability with an increase in temperature from 25 degrees to 45 degrees at
      75% and 100% RH is 0.0 to 25.2%. The results indicate that moisture sorption by
      tablet matrix through certain packaging materials may adversely affect the
      hardness and friability characteristics.

PMID- 16414759
TI  - Review: scheduling drugs and national legal controls the need for research.
AB  - The system of scheduling narcotic drugs and psychotropic substances under
      national legislation does not always correspond to the system of scheduling under
      the international drug control treaties. Even though many drugs have been
      scheduled under the international drug control treaties, few studies have been
      done to identify what happens when drugs are scheduled at the national level.
      Preliminary studies seem to indicate that non-availability and higher prices are
      two problems which are associated with the scheduling process at the national
      level. Further research is needed to have a better understanding of the dynamics
      of the scheduling process and the impact of national controls.

PMID- 16414760
TI  - Short communication: characterization of streptolysin s (sls): storage and
      stability.
AB  - The stability of streptolysin S during storage under different conditions has
      been studied. It is completely stable in 0.1% (w/v) bovine serum albumin
      supplemented with 20% (v/v) glycerol at -20 degrees C for more than 6 months. The
      in vitro study suggests that removal of SLS from cellular environment subjects it
      to variety of conditions and processes that can lead to loss of activity.

PMID- 16414761
TI  - A study on comparative efficacyof hypolipidemic drugs.
AB  - A study was carried out on the comparative efficacy of Lopid, Mevacor, Bezalip
      and Lasona in sixteen hyperlipidemic subjects. All the subjects were on Lopid at
      least for the last 15 days. Lopid therapy was discontinued after determining
      blood lipid profile of the subjects on day zero (day of 1st contact). The
      subjects were divided into three groups and after a washout period of 15 days,
      they were given three different drugs for the next 15 days. Subjects in group a
      (6), b (5) and c (5) received Mevacor, Bezalip and lasona respectively. In the
      present study mevacor was found to be the most potent hypolipidemic drug in
      lowering blood cholesterol and Low density lipoprotein (LDL) while lopid was most
      effective in keeping blood Triglycerides (TG) and High density lipoproteins (HDL)
      level within the desired limits. Bezalip and Lasona were also sufficiently
      effective in changing blood lipid profile, but lasona showed a negligible effect
      on HDL rise as compared with Bezalip or any other drug used in this study.

PMID- 16414762
TI  - Acetylation percentage method for determination of acetylator status in human
      volunteers and tuberculous patients.
AB  - Acetylation percentage method described here is rapid and economical. A
      comparison has been made between plasma half life (t (1/2)), acetylation ratio
      and acetylation percentage methods for the determination of phenotyping.
      Isoniazid (INH) was selected as a test drug. In 120 healthy volunteers and 60
      tuberculosis patients, acetylation percentage method has been found simple and
      reliable as compared to the other methods.

PMID- 16414763
TI  - Antifasciolic efficacy of indigenous plant drugs: kalonji, shahterah and karanjwa
      in buffaloes.
AB  - A study was carried out to evaluate antifasciolic effect of powdered plant drugs
      including Kalonji (Nigella sativa seeds), Shahterah (Fumaria parviflora aerial
      parts) and Karanjwa (Caesulpinia crista seeds) in buffaloes. During the search
      for the infected animals, prevalence of fascioliasis in the random samples was
      33.1 +/- 0.7% but in symptomatically suspected cases it came to be 64 +/- 3.2%.
      The drug trial results showed that all the three drugs possess significant
      efficacies against fascioliasis. Their highest doses tested produced highly
      significant (P<0.001) decrease in EPG counts on 15th days. Maximum antifasciolic
      efficacy, judged on the basis of % EPG count reduction was shown by Shahterah
      (93.2 +/- 0.5%) which was followed by Karanjwa (89.7 +/- 1.7%) and Kalonji (88.2
      +/- 0.4%). No visible side effects were produced by any of these plant drugs.
      Single oral treatment with 25 mg/kg of Kalonji or 60 mg/kg of Shahterah and 40
      mg/kg of Karanjwa exerts highly significant antifasciolic efficacies on the day
      15 after treatment. From these data, it is conceivable that at these dosages the
      drugs are sufficiently potent and safe to treat fasciola infection in buffaloes.
      However, further chemical and pharmacological studies would decide the exact
      mechanism(s) of action, the active principles contained and the real worth of
      these indigenous drugs for the treatment of fascioliasis in the ruminants.

PMID- 16414764
TI  - Antimicrobial studies of the leaf of cannabis sativa L.
AB  - In vitro antimicrobial studies were conducted with aqueous, ethanolic and
      Petroleum ether extracts of the leaves of Cannabis sativa L. The acidic fraction
      was obtained from the ethanolic extract and 2% Sodium Hydroxide extract.
      Ethanolic extract, petroleum ether extract and the acidic fraction exhibited
      activity both against Gram-positive and Gram-negative bacteria and also against
      the fungi used in the study. The aqueous extract however, did not show any
      antimicrobial activity.

PMID- 16414765
TI  - Conductometric study of interaction between dyes and surface active agents.
AB  - The interaction of anionic surface active agents e.g. sodium decyl sulphate
      (SDS), sodium dodecyl sulphate (SDDS), sodium tetradecyl sulphate (STDS), sodium
      hexadecyl sulphate (DHDS) and sodium octadecyl sulphate (DODS) with cationic
      dyes, methylene blue (MB), crystal violet (CV) acridine orange (AO), rhodamine 6G
      (Rh 6G) and quinacrine dihydrochloride (QD) has been studied in three regions by
      conductometric titration. In the first region ion pair association occurs and the
      species (cationic and anionic) exist in equilibrium with homogeneous solution. In
      the second region complexation occurs by 1:1 with MB, CV and AO and by 2:1 with
      QD and Rh 6G forming a heterogeneousphase, separation and equilibration
      containing free ions and ion-pair. In the third region the micelle formation
      occurs by the excess of anions in the presence of cations as well as ion-pair
      formation and separated complex ions that give solubilization of the complex to a
      homogeneous clear solution.

PMID- 16414766
TI  - Effect of cimetidine, ranitidine and tiotidine on plasma testosterone and
      luteinizing hormone levels in rats.
AB  - This investigation was carried out to study the comparative effects of
      cimetidine, ranitidine and tiotidine on the plasma levels of testosterone and
      luetinizing hormone under local conditions. The three H(2)-blocking drugs were
      injected to the adult male albino rats twice daily at the recommended therapeutic
      dose levels for six weeks. The data obtained showed that only tiotidine caused a
      significant (<0.05) increase in the level of testosterone. However, all the three
      drugs caused a significant rise in the levels of luteinizing hormone with the
      most active ranitidine administration.

PMID- 16414767
TI  - Studies on the antimicrobial activity of honey.
AB  - Ten samples of crude and processed honey were used to determine antimicrobial
      activity against twenty five species of pathogenic and nonpathogenic bacteria,
      commonly encountered in human infections. The antifungal activity was checked
      against ten parasitic and saprophytic fungi. Most of the samples of honey used in
      the study showed broad spectrum antibacterial and promising antifungal activity.

PMID- 16414768
TI  - Short communication: guidelines to good manufacturing practices (g.m.p.) in
      pharmaceutical manufacturing.
AB  - The object of the GMP and associated rules is the assurance of the quality of the
      products for the safety, well being and protection of the patient. In achieving
      this aim it is impossible to over-emphasise the importance of people, at all
      levels, in the assurance of the quality of medicinal products. The great majority
      of reported defective medicinal products has resulted from human error or
      carelessness and not from failure in technology. All the people involved with the
      production, quality control or distribution of medicinal products, whether key
      personnel, production or quality control staff, inspectors or other involved in
      the many activities which lead to a patient taking a medicine, should bear this
      constantly in mind when performing their duties.

PMID- 16414769
TI  - Short communication: studies on punica granatum-I isolation and identification of
      some constituents from the seeds of punica granatum.
AB  - Initial phytochemical screening of the seeds of Punica granatum has revealed the
      presence of Ursolic acid and beta-Sitosterol alongwith a long straightchain
      hydrocarbon - nonacosene. Presence of estrogens and glycosides have also been
      detected.

PMID- 16414770
TI  - A comparative study and behaviour of a series of cationic surfactants towards the
      degree of the basic hydrolysis of p-nitrophenyl acetate.
AB  - The surfactant effect of cationic micelles of Dodecyl, tetradecyl and hexadecyl
      trimethyl ammonium bromide, Cetyl pyridinium bromide, Cetyl dimethyl ethyl
      ammonium bromide and benzalkonium chloride on the hydrolysis of p-nitrophenyl
      acetate (PNPA), was studied. The effect of cationic surfactants was within
      concentration range of 1 x 10(-6) M - 1 x 10(-1) M, with the exception of
      benzalkonium chloride, where the concentration effect was investigated between 1
      x 10(-6) M - 3 x 10(-1) M. All cationic micelles increased the rate of hydrolysis
      of PNPA upto their concentration of 1 x 10(-2) M and then the rate decreased
      while benzalkonium chloride showed this maximum at 5 x 10(-2) M. Orientation and
      adsorption of substrate at the micelle surface are put forwarded to explain this
      catalytic behaviour. An attempt has also been made to interpret the influence of
      cationic micelles on the basis of ion exchange model.

PMID- 16414771
TI  - Chemical constituents from the seeds of Pongamia pinnata (L.) Pierre.
AB  - Six compounds (two sterols, three sterol derivatives and one disaccharide)
      together with eight fatty acids (three saturated and five unsaturated) have been
      isolated from the seeds of Pongamia pinnata. Their structures were elucidated
      with the help of physico-chemical methods and spectroscopic techniques. The
      metabolities, beta-sitosteryl acetate and galactoside, stigma sterol, its
      galactoside and sucrose are being reported for the first time from this plant.
      The saturated and unsaturated fatty acids (two monoenoic, one dienoic and two
      trienoic) were present in exactly the same amount. Oleic acid occurred in highest
      amount (44.24%), stearic (29.64%) and palmitic (18.58%) acids were the next in
      quantity. Hiragonic and octadecatrienoic acids were present in trace amounts
      (0.88%).

PMID- 16414772
TI  - Determination of equilibrium constant of ascorbic acid and benzoic acid at
      different temperature and in aqueous and non-aqueous media.
AB  - Dissociation constant studies of ascorbic acid and benzoic acid has been carried
      out potentiometrically at various temperature from 25 to 50 degrees C and in 10,
      20, 30 and 40 percent dioxane-water solvent system at 25 degrees C. Effect of
      temperature and solvent concentration on pKa values has been observed. The
      resolution of acid strength in dioxane-water relative to that in water has been
      determined for both compound by plotting pKa values vs percent composition of
      solvent. The results shows greater resolution in non-aqueous media as compare to
      aqueous media. Data obtained is analyzed by Computer program written in GW-Basic
      for calculation of pKa values for monobasic acid.

PMID- 16414773
TI  - Enicostema littorale: a new source of swertiamarin.
AB  - Enicostema littorale a useful medicinal herb was subjected to phytochemical as
      well as pharmacological investigations. A secoiridoid glycoside, swertiamarin,
      was isolated and identified on the basis of UV, IR, Mass and NMR spectroscopic
      measurements. However, pharmacological studies on the blood pressure of rats and
      ileum of Guinea-pig could not provide significant results.

PMID- 16414774
TI  - Enzymatic activities of some snake venoms from families Elapidae and Viperidae.
AB  - Alkaline phosphomonoesterase, phosphodiesterase, L-amino acid oxidase,
      hyaluronidase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A2 and
      proteinase activities were determined in eight snake venoms, including three from
      sea snake, of families Elapidae and Viperidae from Pakistan. The species includes
      three sea snakes Hydrophis cyanocinctus, Enhydrina schsitosa, Microcephalophis
      gracilis gracilis and two land snakes Naja naja naja, Bungarus caeruleus of
      family Elapidae while three land snakes Vipera russelli russelli, Echis carinatus
      and Eristocophis macmahoni of family Viperidae. The venoms of family Elapidae are
      characterized by low levels to traces of proteinase, L-amino acid oxidase and
      arginine ester hydrolase activities with the exception of Naja naja naja and a
      moderate to high levels of phospholipase A2 activities. The venoms of family
      Viperidae, on the other hand, are characterized by the presence of moderate to
      high levels of 5'-nucleotidase, proteinase, phosphodiesterase and
      phosphomonoesterase activities.

PMID- 16414775
TI  - Quality assurance in nuclear medicine--biological quality control of
      radiopharmaceuticals.
AB  - Quality assurance is the sum of all parameters concerning the preparation and
      control of a finished product. It is a wide term commonly used for the
      confirmation and validity of various ways and measurements adopted to obtain a
      high quality procedure for intended use with guaranteed performance. Biological
      quality control of pharmaceutical products becomes essential as they are
      ultimately to be consumed by living organisms, in particular the humans. In this
      review, we have discussed the importance and significance of biological quality
      control in nuclear medicine. The current and new procedures for sterility,
      apyrogenecity and the biodistribution quality control, have been discussed and
      evaluated in view of the future needs and modern trends in this important area of
      research.

PMID- 16414776
TI  - Studies of the effects of Dexamethasone sodium phosphate on weight of bone
      (tibia) in mice.
AB  - Seventy two immature male and female mice were taken and divided into three
      groups, 24 mice remained untreated and 24 male and female mice were treated upto
      six weeks with daily dose of Dexamethasone phosphate. Twenty four similar mice
      were given injections of vehicle in which the drug, dexamethasone was suspended
      and this acted as placebo group. Dexamethasone treated mice group showed less
      tibia weight as compared to control and placebo group.

PMID- 16414777
TI  - Liposomes preparation methods.
AB  - In this article information about various methods of liposome preparation
      (including the large scale manufacture) has been reviewed. The advantages and
      disadvantages of the methods have been described in terms of size distribution
      and encapsulation efficiency.

PMID- 16414787
TI  - Neurochemical and behavioural effects of diazepam: evidences from animal models.
AB  - Neurochemical and behavioural research show that benzodiazepines (BZs) are the
      well-known anxiolytic drugs which are also used for the treatment of epilepsy,
      hypnosis and insomnia. Administration of BZs to experimental animals produces
      anxiolytic-like effects in various animal models and decreases exploratory
      activity. A role of serotonin (5-HT; 5-hydroxytryptamine) in both anxiolytic and
      anti-exploratory effects of BZs have been suggested. Drugs which mimic 5-HT
      function at the post synaptic sites have been shown to decrease anxiety in
      experimental animals. The present study analyses regionally specific effects of
      BZs on brain serotonin metabolism in relation to the reported behavioural and
      therapeutic profiles of the drugs.

PMID- 16414788
TI  - Rates of formation of anhydronucleosides and comparison with their corresponding
      oxy analogues.
AB  - Anhydronucleosides are reactive intermediates in the synthesis of modified
      nucleosides. Their rates of cyclization of 2,2'; 2,3' and 2,5'-anhydro 2
      thiouridine were studied and compared with their oxy analogues. The order of
      displacement of the leaving group is as follows: 2' > 5' > 3'. It was also
      observed that the rates of cyclization onto the 5' or 3'-position was about 70
      times faster in 2-thiouridine series as compared with the uridine series.
      Similarly the rate of formation of 2, 2'-anhydronucleoside is nearly 2 orders of
      the magnitude faster in the case of thionucleosides.

PMID- 16414789
TI  - Organochlorine pesticide residues in human blood in the population of Multan
      (Pakistan).
AB  - Organochlorine pesticide residues were monitored in samples of human blood
      (N=32), obtained from concerned volunteers suspecting oral, dermal, or inhalation
      exposure to Endosulfan and Heptachlor, either environmentally, or occupationally,
      either recently or in the recent past of Multan Division, (Pakistan) during 1995
      96. The pesticide residues were extracted with n-hexane; detection and
      quantification was performed by gas chromatography (Shimadzu GC 14-A) with a 63Ni
      Electron Capture Detector (ECD). Residues of Endosulfan were found higher as
      compared to Heptachlor in all samples. The highest concentration of Endosulfan
      residues in blood in the population of Multan and Mailsi regions was 90.29 g/kg
      and 82.14 g/kg, lowest as 58.13 g/kg and 60.13 g/kg while Heptachlor had highest
      level as 12.978 g/kg and 9.997 g/kg, minimum as 0.37 g/kg and 1.23 g/kg
      respectively.

PMID- 16414790
TI  - Caesalpinia bonduc (L.) Roxb. seed oil: lipid composition assessment.
AB  - Thirty different fatty acids of various classes were extracted from the non-polar
      fraction of the seeds of Caesalpinia bonduc (L.) Roxb. (Caesal-piniaceae). Eight
      among them were found to be saturated while 22 were unsaturated acids, which
      included nine monoenoic, five dienoic, seven trienoic and one polyenoic acid.
      Unsaturated fatty acids were present in a large proportion (65.76%) than the
      saturated ones (34.24%). Spectroscopic methods (GLC and GC-MS) were used for
      their characterization and identification. Hexadecadienoic acid occurred in the
      highest proportion (21.17%). The single polyenoic acid (tetracosapentaenoate) was
      rare and present in traces (0.95%).

PMID- 16414791
TI  - The role of osmotic diuretics in the management of eclampsia in Karachi women.
AB  - In the present work, out of eighty (80) patients selected, suffering from
      eclampsia, thirty-five (35) were subjected to the combined therapy of diazepam (7
      Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1, 4-benzo-diazepin-2-one) and mannitol
      (Osmotic diuretic) and forty-five (45) patients were administered diazepam only.
      Consequently it was inferred that osmotic diuretic (mannitol) exhibits beneficial
      effects on the management of eclampsia, thereby lowering the mortality and
      morbidity.

PMID- 16414792
TI  - Effects of cinchocaine cocaine analogs on brain mono amines and their metabolites
      in male mice.
AB  - Cinchocaine analogs were studied to determine the effects of acute administration
      of cocaine analogs on dopamine, 5- hydroxytryptamine (5-HT) and their
      metabolites. Psychomotor stimulants, (such as cinchocaine), potently influencing
      dopamine transport carrier were used to characterize in-vivo DA transmission. DA,
      DOPAC, HVA level and indoleamine were measured in brain after drug
      administration. Significant changes in levels of DA, DOPAC, 5-HT, 5HIAA and HVA
      were noted. The present findings suggests that acute administration of
      cinchocaine increases the level of Dopamine, 5-HT and their metabolites and alter
      the level of amines as compare to control group. These studies also indicate that
      difference in structure do not affect the binding sites and inhibition of amine
      uptake.

PMID- 16414793
TI  - Treatment of superficial mycoses.
AB  - Superficial fungal infection of the skin is treated with the help of systemic and
      topical medicaments. Commonly used drugs include griseofulvin, Ketoconazole and
      terbinafine. The drugs have undergone a wide research. In the following these
      drugs have been discussed.

PMID- 16414794
TI  - Therapeutics: a state of the art.
AB  - In Pakistan also there has been tremendous awareness of questions relating the
      safety, efficacy, quality and economic value of drugs. Professionals are equally
      concerned about these vital aspects, but it has been felt that there is a
      communication gap between regulatory authorities, institutions, doctors,
      pharmacists, pharmacologist and the public on various matters concerning drugs.
      Most potent drugs like antibiotics, psychotropic, narcotics, anticancer, hormones
      are being misused by un-trained doctors or by quacks or through self medication
      due to lack of co-ordination among the relevant professionals. It is envisaged
      that the term therapeutic must be adopted in its real sense and therapeutic
      committees should be constituted at institutional and at community levels to stop
      the hazards of misuse of potent drugs and medicines.

PMID- 16414795
TI  - The position of AIDS in Pakistan, UAE and Jordan.
AB  - AIDS is a term used for Acquired Immuno-Deficiency Syndrome. It is, by
      definition, the end-stage disease manifestation of an infection with a virus
      called human immunodeficiency virus (HIV). The virus infects mainly two system of
      the body i.e. the immune system and central nervous system (CNS) and the
      occurrence of disease is due to the damage of these two systems. The statistics
      on AIDS are alarming, especially for Sub-Saharan Africa India. Some scientific
      studies indicated that upto one-third of all sexually active adults living in
      this region are already infected, up to 40% of all women and one in 10 to one in
      5 children born in this part are actively infected with HIV and will be dead
      before having reached their fifth birthday. The information on HIV infected young
      adults were collected both from official and non-official sources of the
      following countries, Jordan, UAE, Pakistan. A big difference in number of
      patients was found between official and non-official data. Anyhow, both data
      (official & non-official) are alarming due to the increase in number of HIV
      cases. 21st century is especially dangerous to the next generation of Pakistan
      and Arab World because of increase in percentage of HIV cases during the last 5
      years.

PMID- 16414796
TI  - Acetates and benzoates of alkyl catechols and evaluation of their antibacterial
      activity.
AB  - Potential biologically active alkyl catechol esters were prepared and their
      antibacterial activity was determined against 12 Gram-positive and 16 Gram
      negative bacteria. Esterification (acetylation and benzoylation) of mono-, di-
      and tetra- substituted alkyl catechols afforded the di-acetyl and di-benzoyl
      derivatives in each case. In the primary screening it was observed that the
      substitution of hydroxyl group in alkyl catechol with an acyl group generally
      resulted in a decrease of antibacterial activity. A number of acetyl and benzoyl
      derivatives inhibited the growth of Salmonella typhi. In case of Gram-positive
      bacteria only di-O-benzoyl-3,5,6,-tetra-(3-hexyl) catechol (26) showed a
      significant activity.

PMID- 16414797
TI  - Curing of R plasmids present in gram negative bacteria isolated from poultry in
      Karachi by ethidium bromide.
AB  - R plasmids of Gram negative bacteria isolated from poultry in Karachi were
      studied for their curing by ethidium bromide (EBr) in E. coli AB 712. Of 12 R
      plasmids studied, 3 were lost by treatment with ethidium bromide.

PMID- 16414798
TI  - Pharmacological evaluation of newly synthesized piperidinium derivatives for
      their analgesic activity.
AB  - Two chemically synthesized piperidinium derivatives i.e l-methyl-1-(3,4)
      dihydroxy phenacyl-4-hydroxy piperidinium chloride and 1-methyl-(4-p) methoxy
      phenacyl 4-hydroxy piperidinium bromide have been evaluated for their analgesic
      activity in intact albino mice by tail immersion method because of their
      structural similarity with opioids. Both the compounds were administered in the
      doses of 50 mg/kg. The results were compared with pethidine used as the reference
      drug. The control animal received only the vehicle. The present study suggested
      that both the compounds exhibit significant analgesic activity.

PMID- 16414799
TI  - Effect of dextran 70 blood substitute on diazepam binding by human serum albumin.
AB  - Diazepam binding studies with dextran 70 and human serum albumin (HSA) were
      carried out using centrifugation and a membrane ultrafiltration technique to
      separate the drug protein complex and the free microsolute. The molecular
      filtration method was found to be precise and reproducible with very little
      variations. The binding of diazepam to dextran was significant but considerably
      smaller when compared with the extensive binding of diazepam to HSA. The results
      of these studies demonstrate that diazepam binding of HSA is altered in the
      presence of dextran. Diazepam binds to dextran resulting in displacement of
      diazepam from albumin binding sites. The contributing effect of dextran to
      overall diazepam binding increased as the dextran concentration increased and the
      HSA concentration decreased. However, the net result of HSA dilution with dextran
      70 was still an increase in the percent free diazepam. Various concentrations of
      dextran 70 significantly displaced HSA bound diazepam in all the mixtures
      studied.

PMID- 16414800
TI  - Comparative bioavailability of sulfamethoxazole in three formulations of
      cotrimoxazole suspensions.
AB  - The pharmacokinetic parameters and relative bioavailability of sulfamethoxazole
      were estimated using three commercially available cotrimoxazole suspensions on
      six human volunteers. Maximum concentration in plasma was shown by product 1,
      i.e., 89.69+/-0.84 and were lower in products 2 and 3, i.e., 38.33+/-0.58 and
      16.50+/-0.89, respectively. The time for maximum concentration was 4 hours in
      products 1 and 3 while it was 3.50 in product 2. There was prolonged elimination
      half-life of formulation 2 (7.50+/-0.94) than formulation 3 (7.43+/-0.54) while
      product 1 (4.54+/-0.15) showed lowest half-life. The values of absorption half
      lives for formulations 1, 2 and 3 were 1.92+/-0.05. 1.80+/-0.41 and 2.78+/-0.25,
      respectively. The volume of distribution was highest in formulation 1 (0.9+/
      0.00) lower in formulation 3 (0.40+/-0.03) and was lowest in formulation 2
      (0.21+/-0.03). The values for total body clearance was lowest i.e., 0.24+/-0.00
      in formulation 1, higher in formulation 2 i.e., 0.35+/-0.05 and still higher in
      formulation 3, i.e., 0.62+/-0.02. By taking the formulation 1, as standard
      (100%), the relative bioavailabilities of formulation 2 and 3 were 79.05 and
      38.53%, respectively.

PMID- 16414801
TI  - Effects of diazepam and cinchocaine on biogenic amines.
AB  - Neurochemical and behavioural research show that benzodiazepines are well know
      anxiolytic drugs, which are also used for the treatment of epilepsy, hypnosis and
      insomnia. Administration of benzodiazepine to experimental animals produces
      anxiolytic-like effects in various animal and decreases exploratory activity.
      Psychomotor stimulants such as cinchocaine also showed potent effect on brain
      biogenic amines and their metabolite. The present studies indicate the changes in
      dopamine and 5-HT and their metabolites levels after acute administration of
      cinchocaine and diazepam.

PMID- 16414803
TI  - Alpha-tocopherol and carcinogenesis.

PMID- 16414802
TI  - Current perspectives and opportunities for international cooperation for
      development of polymer based drug delivery systems.
AB  - The present paper is devoted to: Analysis of significant endeavours directed to
      polymer base drug delivery systems, elucidating addressing priority problems and
      biopolymer development, significant R & D needs and priorities and the framework
      as well as the requirements for international networking in the area of drug
      delivery system. Such organized collaboration will enable promotion of knowledge
      among interested parties and cultures. Concerned pharmaceutical institutional and
      scientific associations e.g. International Pharmaceutical Federation FIP and
      American Association of Pharmaceutical Sciences AAPS should adopt and initiate
      planned activities for developing and activation of appropriate drug network
      encompassing active members from the academic, professional centres and drug
      industry. The proposed network should be established on a self-sustained basis.

PMID- 16414804
TI  - Biological role of anions (sulfate, nitrate, oxalate and acetate) on the
      pharmacological properties of cobalt(II) and nickel(II) chelates with thienoyl-
      and furenoyl-derived compounds.
AB  - Biologically active complexes of cobalt (II) and nickel (II) with thienoyl- and
      furenoyl-derived Schiff-base ligands having the same metal ion but different
      anions such as sulfate, nitrate, oxalate and acetate have been prepared and
      characterized. In order to evaluate the role of anions on their pharmacological
      properties the synthesized complexes have been screened against bacterial
      species, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and
      results have been reported.

PMID- 16414805
TI  - The neurochemical profile of long term oral administration of moclobemide.
AB  - Moclobemide, a benzamide derivative, predominantly inhibits the A form of
      monoamine oxidase (MAO) and its MAO binding is reversible. Acute administration
      of moclobemide has been shown to induce an increase in brain levels of monoamines
      and a concomitant decrease in their respective metabolite. In the present study,
      the drug was administered to rats orally in drinking water at doses of 0.5-1.0
      mg/day/rat of an average weight of 250 g for three weeks. This was equivalent to
      the recommended human dose of 150-300 mg/day. The drug administration did not
      alter food intake, growth rate and activity of rats. Brain levels of 5
      hydroxytryptamine (5-HT) and dopamine (DA) increased. However, increases in 5
      hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) as reported in acute studies were not observed following
      chronic drug administration in the present study in addition, an increase in
      brain levels of tryptophan also occurred. Neurochemical profile of long-term
      moclobemide administration is explainable in terms of an inhibition of MAO
      activity, increased availability of 5-HT precursor tryptophan and decreased
      egress of monoamine metabolites.

PMID- 16414807
TI  - Colicin production/resistance associated with R-plasmids of Gram negative
      bacteria isolated from poultry in Karachi.
AB  - R plasmids of Gram negative bacteria isolated from poultry in Karachi were
      studied for their properties of colicin production and resistance. Of 39 R
      plasmids studied, 23 resisted colicin where as only one R-plasmid produced
      colicin.

PMID- 16414806
TI  - Synthesis and anti-microbial screening of some piperidine derivatives.
AB  - Synthesis of piperidine derivatives viz, 1-(4'-methoxy phenacyl)-N-methyl
      piperidinium bromide, and 1-(4'-nitrophenacyl)-N-methyl piperidinium bromide, and
      1-(3', 4'-dihydroxy phenacyl)-N-methyl piperidinium chloride was carried out by
      quarternizing N-methyl piperidine with corresponding phenacyl halides. The
      structures of these compounds were elucidated by spectroscopic techniques such as
      UV, IR, EI mass and 1H-NMR. The compounds were subjected to antimicrobial
      screening in quantities of 10 mg/ml dissolved in DMSO. Disc diffusion method was
      used to observe the significance of these compounds against seven bacterial and
      one fungal cultures.

PMID- 16414808
TI  - Changes in physical and chemical constituents of crab meat during storage at
      refrigerator temperature (7+/-2 degrees C).
AB  - The present study was initiated to determine the deteriorative changes occurred
      in the nutritive quality of crabmeat during storage at refrigerator temperature
      (7+/-2) for the period of one week. The parameters studied for the assessment of
      quality are pH, water, total protein and salt soluble protein, TMA-N, TVB-N
      content. The results indicate a significant increase (p < or = 0.001) in pH,
      water, TMA. TVB while total protein salt soluble protein, and total lipid
      contents were significantly decreased (p < or = 0.001) as compared to fresh
      tissue. Our finding recommended that the quality of crabmeat is acceptable upto
      one day of storage at refrigerator temperature after that it becomes
      deteriorated.

PMID- 16414809
TI  - Effects of socioeconomic factors, psychological stress, smoking, alcohol and
      caffeine on preterm delivery.
AB  - The relation between preterm birth and socioeconomic and psychological factors,
      smoking, alcohol and caffeine consumption are studied. Gestational age was
      determined from ultrasound and maternal dates. Adverse social circumstances are
      associated with preterm birth which inturn effects fetal growth.

PMID- 16414810
TI  - Effect of disintegrants and hardness on the disintegration time of Acetaminophen
      tablets.
AB  - In this study the effect of various disintegrates on the disintegration time of
      laboratory prepared Acetaminophen tablets at different hardness has been
      determined. The disintegration time was found to be directly related with the
      hardness of the tablets for all formulations studied except in tablets containing
      veegum.

PMID- 16414811
TI  - Assessment of Anemone pulsatilla for some biological activities.
AB  - Preliminary screening of herbal extracts employs the determination of their
      biological activity and the estimation of their therapeutic potential. This
      eliminates the unnecessary effort of fractionation and purification of
      constituents unimportant from the practice pharmacological point of view. It also
      gives a scientific basis to the herbs traditionally used in folk medicine. Thus,
      during the present investigation the spasmolytic effect of Anemone pulsatilla
      extract on isolated tissues of rabbit jejunum was evaluated. In addition the
      pharmacological screening of Anemone pulsatilla extract was also earned out.

PMID- 16414812
TI  - Viscosity studies on Mestranol.
AB  - The viscosity of 1x10(-4) M to 4x10(-4) M solution of Mestranol (synthetic
      oestrogenic steroidal hormone) in ethanol was measured at 32 degrees, 40 degrees
      and 50 degrees C in a viscometric bath. The viscosity rates are maximum at 30
      degrees C as compared to 40 degrees and 50 degrees C. The disappearance rate of
      Mestranol at higher temperature and lower viscosity is due to triplet state of
      species transitions at higher thermal conditions.

PMID- 16414813
TI  - Platelet Activating Factor antagonists.
AB  - Platelet Activating Factor (PAF) is a D-glycerol derived phosopholipid which is a
      potent endogenous mediator of inflammation. PAF is synthesized and released by a
      variety of cell types and elicits its biological activity by interacting with
      specific G-protein coupled receptors found on platelets, neutrophils, and other
      inflammatory cells. The physiological consequences of the interaction on PAF with
      its receptor include an increase in vascular permeability, hypotension,
      bronchoconstriction, and platelet and neutrophil aggregation. These biological
      effects are consistent with the concept that PAF is involved in a number of
      inflammatory diseases such as septic shock and asthma (Arimura A., 1998). Given
      the potent pathophysiological effects of PAF, a great deal of effort has been
      focused on the discovery of agents which block the action of PAF at its receptor.
      Within the past 10 years, a wide range of structures have been identified as PAF
      antagonists. These include not only PAF analogs, but also antagonists derived
      form natural product as well as non-lipid synthetic compounds. Several theories
      have been proposed to unify these diverse structural classes, but sophisticated
      molecular models of the receptor have not been widely employed (Braquet P.,
      1987). The discovery of new PAF antagonists has relied heavily on traditional
      medicinal chemistry approaches. A number of PAF antagonists have advanced to
      clinical evaluation. While several early compounds demonstrated efficacy in
      animal models of asthma they have failed to provide benefit for this condition in
      man. The current generation of potent antagonists are being evaluated as
      therapies for sepsis, pancreatitis and other disorders (Braquet C., 1991).

PMID- 16414814
TI  - Phytochemical and antimicrobial studies of Salvia splendens Sello.
AB  - The phytochemical investigation of antimicrobial agents from locally occurring
      Salvia splendens Sello, was carried out. Three common solvents i.e. petroleum
      ether (40-60%), chloroform and methanol were successively used for the extraction
      of antimicrobial principles from its various parts. Three major compounds (namely
      C1, C2, and C3) were isolated and purified from the active methanol extract of
      roots by column and thin layer chromatography. Gram-positive bacteria (Bacillus
      pumilus, B. subtilis and Staphylococcus aureus), Gram-negative bacteria (Proteus
      vulgaris, Escherichia coil and Pseudomonas aeruginosa) and a fungus (Candida
      albicans) were used to measure the zones of inhibition of these compounds by
      known method. One of the compound C1 gave larger zones than the other two
      isolated compounds (C2 and C3). An attempt was made to identify the nature of
      antimicrobial compounds by available spectral means. A possible structure
      activity relationship of the potent antimicrobial compounds was discussed.

PMID- 16414815
TI  - Effect of chlorpromazine on brain biogenic amines in normal and hyperglycemic
      state.
AB  - In present study the effects of chlorpromazine (CPZ) were studied on NA, DA and
      its metabolities i.e. DOPAC and HVA as well as on 5-HT and its metabolite 5-HIAA
      in normal and hyperglycemic rats. Significant differences were noted in brain
      biogenic amines of normal and diabetic control animals. In case of CPZ treated
      normal and hyperglycemic rats significant differences were observed only in case
      DOPAC and 5-HIAA. NA and 5-HIAA levels were significantly affected by CPZ and
      diabetes interaction.

PMID- 16414816
TI  - Resistance pattern of clinical isolates from cases of chronic ear infection II.
AB  - During present study hundred clinical isolates from cases of ear infection were
      tested from local population for resistance pattern, using eleven different
      antibiotics. A considerable percentage of isolates causing ear infection was
      resistant to number of antimicrobial drugs. The percentages of organisms isolated
      from ear infection are Pseudomonas aeruginosa (50%), Proteus species (16%),
      Staphylococcus aureus (15%), Klebsiella species (13%) and Escherichia coli (6%).

PMID- 16414817
TI  - Comparative analysis of pulsed (activated) and resting chicken cytochrome c
      oxidases with sodium chloride dependence of the enzyme.
AB  - Comparative investigation of pulsed (activated) chicken cytochrome c oxidase and
      resting enzyme are compared with other species and pH dependent properties are
      also monitored Sodium chloride dependence of chicken oxidase is analysed and
      compared with that of beef cytochrome c oxidase. Carbon monoxides binding and
      spectral changes during this process are also discussed. S values are also
      determined at different pH of the enzyme ultra centrifugation.

PMID- 16414818
TI  - High performance liquid chromatographic determination of isoniazid, pyrazinamide
      and rifampicin in pharmaceutical preparations.
AB  - lsoniazid (IS) individually or in the presence of pyrazinamide and rifampicin has
      been determined by high performance liquid chromatography (HPLC) after
      derivatization with 6-methyl-2-pyridinecarboxaldehyde. Pyrazinamide and
      rifampicin separate completely from isoniazid derivative and are determined
      simultaneously. The chromatography is carried out from YMC-ODS column with
      elution with methanol: water: isopropanol: acetonitrile: sodium acetate (1 mM)
      51:42:3:2:2: v/v/v/v/v/) with flow rate 1.7 ml/min and UV detection at 333 nm.
      The method is applied for the analysis of Isoniazid B.P Rambuzid and Myrene-p
      tablets.

PMID- 16414819
TI  - Neurochemical and behavioural effects of long term intake of tea.
AB  - Tea consumption in many cases is the main source of caffeine intake in humans. In
      the present study neurochemical and behavioural effects of long-term tea intake
      are monitored in rats. Long-term tea administration did not alter plasma
      tryptophan (TRP) but significantly attenuated brain TRP and 5-hydroxytryptamine
      (5-HT, serotonin) levels. Brain 5-hydroxyindole acetic acid (5-HIAA) was
      comparable in both tea-treated and control rats. An increase in home cage
      activity was observed after one week in rats taking tea as sole source of liquid,
      whereas no change on the activity was observed in an open field. Caffeinism has
      been associated with depression. The decreases of brain monoamine metabolism
      observed in present study are discussed as lowering of mood observed in tea or
      coffee consumers.

PMID- 16414820
TI  - Synthesis, spectroscopic and biological studies of some mono- and di-substituted
      hydrazine-derived ferrocenes.
AB  - Some mono-and disubstituted hydrazine-derived ferrocenes have been synthesized
      and studied for their antibacterial properties. All these synthesized compounds
      have been characterized by their physical, analytical and spectral data, which
      introduces a novel class of ferrocene compounds. The antibacterial properties, of
      these compounds have also been evaluated and thus a significant use of such
      compounds as antibacterial agent is reported.

PMID- 16414821
TI  - A survey of antibiotic resistance among E. coli strains isolated from poultry in
      Karachi.
AB  - Studies were carried out to investigate the incidence of multiple antibiotic
      resistance among E .coli (total 152) isolated from poultry in Karachi to eight
      commonly used antibiotics: ampicillin (A), chloramphenicol (C), gentamycin (G),
      anamycin (K), neomycin (N), polymyxin B (P), streptomycin (S) and tetracycline
      (T) at the levels of 50 microg/ml, 100 microg/ml and 500 microg/ml. Tables of the
      results are given, showing the number of resistant strains of different patterns
      of antibiotic resistance at different levels. A comparison of antibiotic
      resistance to different number of antibiotics and the frequency of resistance to
      individual antibiotic at different levels is also reported. The highest frequency
      of resistance was against tetracycline whereas the lowest frequency of resistance
      was against gentamycin. Thirty R plasmids were isolated from the resistant
      strains and will be reported elsewhere.

PMID- 16414822
TI  - Cardiac and intestinal contractions under the influence of triturated drug
      dilutions.
AB  - Triturated dilutions of acetylcholine and adrenaline are found to produce reverse
      effects than their parent one on the mechanical performance of mammalian heart
      and intestine in vitro. However, there is a variation in the magnitude of reverse
      response observed for both the tissues. It is concluded that variation in the
      effect of triturated dilutions is probably due to handling and shaking of the
      diluted drug before use in experiments. In addition, no relation exists between
      degree of dilution and the magnitude of response for both the tissues.

PMID- 16414823
TI  - Increased precursor availability did not increase food intake and 5-HT turnover
      rate in the hypothalamus of diazepam injected rats.
AB  - In view of a possible role of serotonin (5-hydroxytryptamine; 5- HT) in
      regulation of appetite and anxiety, the effects of 1, 3 and 5 mg/kg doses of
      diazepam on brain serotonin precursor and effects of single and repeated diazepam
      (1 mg/kg 2* daily for 4 days) administration on hypothalamic 5-HT, 5
      hydroxyindoleacetic acid (5-HIAA and 5-HIAA/5-HT ratio are investigated in rats.
      Daily diazepam treatment decreased food intakes. Diazepam injected rats exhibited
      a dose-dependent increase of tryptophan in the hypothalamus. Administration of
      diazepam (1 mg/kg) to 4 day saline injected rats on the 5th day increased 5-HT
      and decreased 5-HIAA levels in the hypothalamus. 5-HIAA/5-HT level also
      decreased. 4-day diazepam injected rats injected with saline on the 5th day also
      exhibited similar changes of 5-HT. 5-HIAA and 5-HIAA/5-HT ratio. Administration
      of diazepam to 4 day diazepam injected rats again decreased 5-HIAA concentrations
      but did not increase 5-HT levels in the hypothalami of rats. Possible mechanism
      involved in the anorectic effects of diazepam-induced changes of hypothalamic 5
      HT turnover rate is discussed.

PMID- 16414824
TI  - Pharmacokinetic study about interaction of Naproxen and Isoniazid.
AB  - Effect of Naproxen (500 mg) was studied on the pharmacokinetic characteristics of
      Isoniazid (300 mg) in ten healthy human volunteers in a complete crossover
      design. A high performance liquid chromatography (HPLC) method was used to
      analyze serum drug concentrations. Naproxen caused a highly significant (P<0.001)
      increase in AUC, significant (P<0.05) increase in elimination half life (t(1/2))
      and time for the maximum drug concentration (tmax) while significant (P<0.05)
      decrease in elimination rate constant (Kc). Insignificant decrease and increase
      was observed in absorption rate constant (Ka) and maximum drug concentration
      (Cmax) respectively.

PMID- 16414826
TI  - A study on the effects of some new derivatives of piperidine on
      neurotransmitters.
AB  - Four chemically synthesized derivatives of piperidine were subjected to evaluate
      their pharmacological actions on Nervous System in male albino mice. The effects
      on neuro-transmitters such as catecholamine and indolamine assuming that these
      derivatives might alter them differently, studied by HPLC-EC method. The result
      revealed that brain dopamine and catecholamine were altered by most of these
      derivatives at the doses of 100 mg/kg body weight.

PMID- 16414825
TI  - Swelling behaviour of pH-sensitive crosslinked poly(vinyl acetate co-acrylic
      acid) hydrogels for site specific drug delivery.
AB  - The present work was undertaken to combine nonionic vinyl acetate (VAC) with
      anionic acrylic acid (AA) or methacrylic acid (MAA) monomers in the presence of
      ethylen glycol dimethacrylate (EGDMA) as cross-linking agent through radical
      polymerization. Poly(vinyl acetate-co-acrylic acid) VAC/AA 50:50 to 100:0 six
      samples and poly(vinyl acetate-co-methacrylic acid) VAC/MAA one sample were
      prepared. All the samples were used for swelling studies. High swelling occurred
      at above pH 5.5 through chain relaxation. It was observed that swelling in
      VAC/MAA was lower than VAC/AA copolymers. The lower swelling in VAC/MAA copolymer
      is due to the presence of hydrophobic methyl group and higher pKa value of this
      copolymer.

PMID- 16414827
TI  - Influence of monovalent cations on the rates of dibromosuccinate and hydroxide
      ions.
AB  - The rate constants for the reaction between dibromosuccinate and hydroxide ions
      have been determined in the presence of lithium and sodium chloride. Effects of
      temperatures and added electrolytes on this reaction have also been examined. It
      has been found that smaller radii have less accelerating effects on the rate of
      reaction. The activation parameters such as apparent energy of activation (Ea),
      change in enthalpy of activation (DeltaH#), change in entropy of activation
      (DeltaS#) and change in free energy of activation (DeltaG#) have been calculated
      in the absence and presence of lithium and sodium chloride for the reaction and
      discussed.

PMID- 16414828
TI  - Inhibition of rat liver tryptophan pyrrolase activity by fluoxetine.
AB  - The present study has demonstrated the effectiveness of acute administration of
      fluoxetine to inhibit rat liver tryptophan pyrrolase activity. The maximum
      inhibition of basal liver tryptophan pyrrolase activity at 2 h after
      administration was observed with 1 mg/kg dose for the total enzyme and apoenzyme
      activities and that significant inhibition of these two activities was evident
      with a dose of the drug as small as 0.5 mg/kg. Serum free tryptophan
      concentrations were also increased using 10 mg/kg dose of fluoxetine. In view of
      the role of tryptophan depletion and thus 5-HT in pathophysiology of depression,
      it is strongly suggested that the inhibition of liver tryptophan pyrrolase
      activity may be a major mechanism of antidepressant action.

PMID- 16414829
TI  - Isolation of a flavone from Polygala stenopetala.
AB  - A flavones has been isolated from the roots of Polygala stenopetala. The
      structure was established on the basis of UV, Mass spectrum, 1HNMR, 13CHMR and
      NOE difference experiments as 5,7,4-trihydroxy-3, 5-dimethoxyflavone (tricin)
      This is for the first time that a flavones has been isolated from the species
      belonging to the family Polygalaceae.

PMID- 16414830
TI  - Role of quinone moiety as antitumour agents: a review.
AB  - Quinone antitumour agents with wide spectrum of activity have been extensively
      used in different forms of human cancers. Quinones have been isolated either from
      animals, microorganisms or plants. Extensive research on quinone compounds is
      going on to discover novel effective antitumour compound. We also discussed the
      mechanism of action, which have not been fully clarified. In this review we cover
      all the above-mentioned aspects to emphasize the importance of quinone moiety as
      antitumour agents.

PMID- 16414831
TI  - The hypolipidaemic effect of gum tragacanth in diet induced hyperlipidaemia in
      rats.
AB  - Previous research indicated that fiber in the diet of men lowers plasma lipid and
      LDL cholesterol concentration. To further study the lipid lowering effect of
      fibre, we conducted an animal study using rats with diet induced hyperlipidaemia.
      Rats were randomly assigned to one of the three experimental diets. Two of the
      diets contained cholesterol and choice acid to induce hyperlipidaemia, the fiber
      source in the hyperlipidaemic diet was gum tragacanth (5%). The rats consumed one
      of the three diets ad libitum for 4 weeks before they were killed. Plasma LDL
      cholesterol and total cholesterol concentrations were significantly higher in the
      hyperlipidaemic group than in the non hyperlipidaemic control group. A marked
      improvement in the plasma LDL cholesterol and total cholesterol concentration was
      observed in the rats that were fed hyperlipidaemic diet containing grum
      tragacanth. No significant difference in the plasma triglyceride concentration
      was detected in the three groups. Plasma HDL concentration was significantly
      higher in the non-hyperlipidaemic group than in the hyperlipidaemic group than.
      Addition of gum tragacanth to the hyperlipidaemic diet significantly improved the
      plasma HDL concentration in the hyperlipidaemic rats. These results suggest that
      fiber from gum tragacanth lowers plasma cholesterol and LDL in hyperlipidaemia.
      Gum tragacanth could be useful adjunct to the dietary management of
      hyperlipidaemia.

PMID- 16414832
TI  - Kinetics of reaction between phenothiazine dye/methylene green and
      peroxydisulphate ion in presence of bromide ion.
AB  - The rate of nuclear bromination was observed when the methylene green reacts with
      peroxydisulphate ion in presence of bromide ion. The reaction obeys zero order
      kinetics in the dye whereas first order kinetics in peroxodisulphate and bromide
      ion. The reaction was studied at various ionic strengths and temperatures to find
      out the effect of ionic strength on rate of nuclear brominating and energy of
      activation. The kinetics pertains to the rate determining stage of
      peroxydisulphate-bromide reaction. The study in different concentration of
      bromide and peroxydisulphate has shown that the rate constant increases by
      increasing the ionic strength and temperature of the system. The effect of ionic
      strength on the activation parameters was also studied.

PMID- 16414833
TI  - A comparative study of omega-3-fatty acids obtained from marine fish and
      bezafibrate alone and in combination as hypolipidemic agents.
AB  - The fish oil and its constituents have been studied in detail with special
      reference to ailments. The discovery of omega-3 fatty acids led to a detailed
      investigation about its effect and role as anti-cholesterolemic agents. The
      effect of fish oil alone and in combination with acid derivatives was found to be
      a potent cholesterol and triglycerides lowering agent. Comparative studies of
      fish oils and bezafibrate led to the formulation of new therapeutic combination
      having lesser side effects and toxicity.

PMID- 16414834
TI  - An investigation into the behaviour of the electrolytes in presence of ionic
      urfactants.
AB  - The effect of various concentrations of Sodium Chloride and Lithium Sulphate in
      presence of Carbonate-bicarbonate buffer at pH 9.20 on the base-catalyzed
      hydrolysis of procaine was investigated. The whole study was done in the presence
      of different concentration of cetyltrimethyl ammonium bromide (CTAB) and Sodium
      dodecyl Sulphate (SDS) at 60 degrees C. Addition of different electrolytes
      suppressed the maxima in the Surfactant Effect Ratio (SER). The presence of these
      additives increase the inhibitory effect with a corresponding in their
      concentrations SDS/SO4, appeared to be most effective inhibitory amongst
      SDS/Li2SO4, SDS/NaCl, CTAB/Li2SO4, and CTAB/NaCl systems.

PMID- 16414835
TI  - Antibacterial cobalt(II) and zinc(II) complexes of pyrazine-derived NNO and NNN
      donor Schiff-bases.
AB  - A series of biologically active pyrazine-derived Schiff-base ligands have been
      synthesized by the condensation reaction of 2-aminopyrazine with salicylaldehyde
      and acetamidobenzylaldehyde. Then their cobalt(II), nickel(II) and zinc (II)
      complexes have been prepared. The biological evaluation of the simple uncomplexed
      ligand in comparison to their complexed compounds have been determined against
      bacterial strains e.g., Escherichia coil, Staphylococcus aureous and Pseudomonas
      aeruginosa.

PMID- 16414836
TI  - Cineole as skin penetration enhancer.
AB  - Cineole is a chief constituent of eucalyptus oil and constitutes almost 80% of
      this essential oil. A study was conducted on skin penetration enhancing capacity
      of cineole (1, 8-cineole) towards the permeation of 5 flurouracil in excised rat
      skin; it caused almost 83 fold increase in drug permeability co-efficient, the
      mode of action of acceleration may be described by combined process of partition
      and diffusion.

PMID- 16414837
TI  - Controlled release coprecipitates of ibuprofen and a carbomer: preparation,
      characterization and in vitro release studies.
AB  - Extended release coprecipitates of ibuprofen (IBF) and carbopol 934P-NF, in the
      form of micro-matrices, were prepared using two different methods. The drug
      carbomer interactions in the solid state were investigated employing Infra Red
      (IR) Spectroscopy, Differential Scanning Calorimetry (DSC), and Scanning Electron
      Microscopy (SEM). Dissolution experiments were performed using simulated gastric
      fluid (SGF- pH 1.2), distilled water, and pH 7.2 phosphate buffer solution as
      dissolution media. No well- defined chemical interaction between the ingredients
      was found. The methods of preparation of the coprecipitates are simple,
      practical, minimize the use of toxic organic solvents, and can be used in the
      production of controlled release tablets.

PMID- 16414838
TI  - Neurochemical and extra pyramidal effects of atypical neuroleptic clozapine in
      rats.
AB  - In view of a possible role of serotonin (5-hydroxytryptamine, 5-HT) and dopamine
      (DA) in neuroleptic-induced muscle rigidity and catalepsy, the present study is
      designed to investigate the neurochemical and extrapyramidal effects of atypical
      antipsychotic/neuroleptic drug i.e., Clozapine (CZP) on the metabolism of
      serotonin and dopamine particularly in the caudate (a region of the brain
      involved in the control of movement), accumbens and rest of the rat brain.
      Interaperitoneal (i.p) injections of CZP at doses of 5.0 & 10 mg/kg decreased
      significantly (p<0.01) locomotor activity in familiar (home cage) environment.
      CZP produced a significant (P<0.01) cataleptic response only at doses of 10 mg/kg
      used. Maximal cataleptic effects in rats occurred at high doses of CZP. Acute
      administration of CZP significantly (p<0.01) decreased levels of NA in accumbens
      at all the doses used. Significant increases (p<0.01) in the levels of NA
      observed in rest of the brain only at moderate dose (5 mg/kg) of CZP. Results
      showed significant (p<0.01) increases in the levels of caudate DA following the
      administration of CZP at 10 mg/kg. However administration of CZP at all the doses
      produced similar significant (p<0.01) increases in the levels of HVA in all the
      regions of the rat brain. Overall insignificant effects of CZP occurred on brain
      regional TRP. However, plasma TRP significantly (p<0.01) increased at 2.5 mg/kg
      dose of CZP. Administration of CZP at doses of 2.5 and 10 mg/kg significantly
      (p<0.01) decreased 5-HT levels in the rest of the brain. Administration of CZP
      produced insignificant (p>0.05) effects on 5-HIAA levels in the caudate and
      accumbens regions but CZP at doses of 2.5 and 5 mg/kg significantly (p<0.01)
      decreased 5-HIAA levels in the rest of the brain. Neurochemical and
      extrapyramidal effects of atypical antipsychotic (clozapine) are discussed in
      relation to a potential therapeutic profile in rats.

PMID- 16414840
TI  - A study on fatty acid composition of fish oil from two marine fish, Eusphyra
      blochii and Carcharhinus bleekeri.
AB  - Two species of marine fish found in coastal waters of Karachi (Pakistan) were
      studied, Eusphyra blochii (Hammer-headed Shark) and Carcharhinus bleekeri (Shark)
      for their fatty acid composition. The isolation, identification and
      characterization of these fatty acids were carried out by gas liquid
      chromatography (GLC) and a combination of TLC-GLC technique. A large variation
      was observed between hammer-headed shark liver oil and shark liver oil. Twenty
      five individual fatty acids from the oil of marine fish were analyzed among those
      the palmitic acid was a major saturated fatty acid while stearic acid was the
      other major constituent. Among unsaturated fatty acids monoenoic e.g. oleic and
      palmitoleic acids were the major constituents and traces of dienoic and trienoic
      fatty acids were also found. In addition medicinally important polyunsaturated
      fatty, acid eicosapentaenoic and docosahexaenoic acids were also identified.

PMID- 16414839
TI  - Antimicrobial activity of some commonly used herbs.
AB  - In the present study some herbal extracts have been tested for their
      antibacterial activity using seven different strains of Gram positive and Gram
      negative bacteria to measure the zone of inhibition. Extracts were found devoid
      of activity against all the microorganisms.

PMID- 16414841
TI  - Correlation between toxic natures of pyrethroid and behavioral response of desert
      locusts.
AB  - Optomotor normal visual response of the locust Schistocerca gregaria was compared
      when injected (between 1st and 2nd thoracic segments) with 10, 5, 2.5 and 1.25
      microg/g body weight doses of Permethrin after different intervals of time (just
      after injection, 10 and 20 minutes). LD50 value for Permethrin was calculated to
      be 3.0 microg/g. Results are analyzed statistically by t. test and ANOVA
      technique. It was noticed that there was a significant decrease of vision
      (P<0.005, Table II) in treated locusts and at the same time Permethrine effect is
      significantly time related (P<0.05, ANOVA, table III). Correlation between
      increasing age, weight and increasing toxicity has also been established. The
      inhibition of neural enzyme Cholinesterase with Permethrin and as a result more
      accumulation of acetylcholine at nerve junctions and less passage of the
      transmission of impulses thus less response from the locusts has also been
      explored and discussed.

PMID- 16414842
TI  - Cyclic voltammetric study of bendrofluazide at a carbon paste electrode.
AB  - Electrochemical oxidation of bendrofluazide was performed using cyclic
      voltammetry at a silicon oil impregnated carbon paste electrode (CPE) vs. Ag|AgCl
      reference electrode. Various qualitative parameters such as Ep, ip, betanb, and D
      were determined in aqueous KCl, NaCl, NH4Cl, KOH, NaOH, NH4OH, HCl, CH3COOH and
      H2SO4 systems. Bendrofluazide showed an irreversible electron transfer process
      with a CPE at 25, 35, and 45 degrees C. The heterogeneous rate constant KE was
      calculated to be 1.3x10(-6) at 25 degrees C. The shape of the CV wave was also
      drawn using simulation method. This obtained profiles similar to that of the
      experimental CV curves at different scan rates Investigation through diagnostic
      tests confirmed the absence of adsorption (either weak or strong) or analyte on
      the surface of the test electrode. The present method provides quantification of
      analyte in the dilution range 10(-4) to 10(-5) M.

PMID- 16414843
TI  - Dissolution rate studies on Acetaminophen tablets.
AB  - The effect of disintegrants on the dissolution rate of Acetaminophen tablets at
      different hardness has been investigated. It was determined that the dissolution
      rate is influenced by disintegrants as well as hardness for all formulations
      except in tablets containing Veegum as the disintegrant.

PMID- 16414844
TI  - Kinetics of bromination of safranine by peroxydisulphate ion in presence of
      bromide ion.
AB  - Kinetics of bromination safranine by peroxydisulphate ion in presence of bromide
      ion has been investigated at various temperatures and ionic strengths. The rate
      followed first order kinetics in peroxy disulphate and bromide ion each, and zero
      order kinetics in safranine. A linear relation was obtained for the variation of
      logarithm of rate constant (log k) with the square root of ionic strength of the
      media (mu). The rate constants for the rate controlling step were evaluated and
      interpreted as a function of ionic strengths and temperatures. The values of
      activation parameters were also computed.

PMID- 16414846
TI  - Cyclic Voltammetric study of colchicine.
AB  - Cyclic Voltammetry reveals the reversible electrode processes during the cyclic
      oxidation-reduction of the colchicine in 0.1 M H2SO4. The behaviour of Peak
      potential with pH was studied to investigate the acid base reaction of the
      species, involved in the electrochemical reaction.

PMID- 16414845
TI  - Cefuroxime antacid interactions.
AB  - Cefuroxime sodium a second generation semi-synthetic cephalosporin is effective
      for treating meningitis, lower respiratory tract infections, gonorrhea, bone and
      joint infections and is approved for surgical prophylaxis. There are number of
      synergistic and as well as antagonistic drug interactions reported for this
      antibiotic. Withstanding to gastric irritations caused by this antibiotic,
      antacids may possibly be co-administered with cefuroxime, which may result in
      severe adverse drug interaction. The present work describes the effect of
      magnesium carbonate, magnesium hydroxide, magnesium trisilicate, megaldrate
      powder, sodium bicarbonate, aluminum oxide and simethicone suspension on the in
      vitro availability of cefuroxime sodium. The mechanism of interaction between
      antibiotic and antacids was also studied.

PMID- 16414847
TI  - Effect of naproxen on the pharmacokinetic parameters of rifampicin.
AB  - The effect of naproxen (500 mg) on the pharmacokinetics of rifampicin (450 mg)
      was evaluated in healthy human subjects (n = 10). Subjects participated in a two
      way crossover trial, the first dosing condition was rifampicin alone (control),
      and the second dosing condition was naproxen with rifampicin. The concentrations
      of rifampicin from the serum samples were determined by HPLC. The pharmacokinetic
      parameters indicated a significant (P < 0.05) increase in elimination rate
      constant (Ke), clearance (Cl), volume of distribution (Vd), while significant
      decrease in the mean residence time (MRT), and area under the concentration-time
      curve (AUC). Insignificant increase and decrease in absorption rate constant
      (Ka), and elimination half-life (t1/2), time for maximum concentration (Tmax),
      maximum drug concentration (Cmax) respectively was observed.

PMID- 16414848
TI  - In vitro effects of acth on pigeon crop-sac epithelium.
AB  - ACTH in vitro produces non-specific crop-sac epithelium response. Crop-sac
      maintained in 10 IU.ACTH in isologous serum at 37 degrees C for 6 hrs. showed an
      increase of 105 +/- 0.95 mg for 12 hrs. 115 +/- 1.13 mg, for 18 hr. 125 +/- 0.95
      mg. and for 24 hrs. 145 +/- 2.31 mg. The results were analyzed statistically by
      ANOVA technique. A significant rise in mean weight. In ACTH treated crop-sac,
      indicates a time related relationship (P < 0.01, ANOVA, Table 2). Thus present
      data indicates that there is a correlation between the epithelial response and
      initiation of ACTH present in the serum.

PMID- 16414849
TI  - Multiple antibiotic resistance among gram negative bacteria isolated from milk in
      Karachi.
AB  - A total of 100 Gram negative bacteria isolated from milk in Karachi were screened
      for their resistance to eleven commonly used antibiotics. The concentration of
      antibiotics used was 100 microg/ml. About 46% were found to resist antibiotics at
      the concentration of 100 microg/ml giving different patterns. The resistant
      bacteria were tested for the presence of R plasmids, both transferable and non
      transferable, by conjugation, spontaneous segregation and curing with acridine
      orange and ethidium bromide. Among the resistant bacteria tested, eight were
      found to carry non-transferable R plasmids.

PMID- 16414850
TI  - Salivary glucose concentrations in patients with diabetes mellitus--a minimally
      invasive technique for monitoring blood glucose levels.
AB  - Salivary and blood glucose concentrations were determined in non-diabetic healthy
      individuals and patients with diabetes mellitus (type II). Glycosylated
      haemoglobin A1c was also determined in some of the patients (n = 25) and a
      significant correlation (r = 0.82) was found between HbAlc and serum glucose
      concentrations in these patients, indicating that these patients had average
      elevated blood glucose concentration over an extended time period. Glucose was
      only found in the saliva of patients with diabetes mellitus (n = 135), while the
      salivary samples of age matched non-diabetic subjects (n = 25) did not show the
      presence of glucose. A significant correlation (r = 0.78) was found between
      salivary and blood concentrations in the diabetics. This finding suggests that
      saliva can be used reliably for reflecting and monitoring the blood glucose
      concentration in the patients of diabetes mellitus.

PMID- 16414851
TI  - Studies on Achras sapotal: part IV--chemistry and pharmacology of wood.
AB  - Phytochemical screening of the n-hexane fraction of the alcoholic extract of
      Achras sapotal has shown the presence of oleane and ursane types of
      triterpenoids. Pharmacology of the alcoholic extract was studied on Wister rats
      anaesthetized with recommended dose. The extract caused a fall in systolic,
      diastolic and mean arterial blood pressure (MABP) in a dose depended manner.

PMID- 16414852
TI  - Synthesis and antimicrobial activities of 1, 2-di (6-methylquinolyl-2) 1, 2
      ethanedion.
AB  - The 1,2-di(6-methylquinolyl-2)-1,2-ethanedion is obtained when 1,2-di(6
      methylquinolyl-2)-1,2-ethenediol was oxidized using air as an oxidizing agent
      whereas the starting material itself was synthesized when 6-methyl quinoline-2
      carboxaldehyde was subjected to condensation reaction in the presence of
      potassium cyanide. The biological screening of the resulting substituted 1,2
      diketone revealed its significant antimicrobial activities.

PMID- 16414853
TI  - Rearrangement of substituted propionanilides.
AB  - The rearrangements of substituted anilides of propionic acid to amino ketones in
      a solvent medium were studied, employing bismuth chloride as a catalyst.
      Rearranged compounds were then characterized by qualitative tests and spectral
      data.

PMID- 16414854
TI  - A pilot study: asymptomatic hyperlipoproteinemias in undergraduate university
      students.
AB  - Young adults may suffer hyperlipoproteinemias, which may be asymptomatic. This
      pilot study was conducted to screen out hyperproteinemias in undergraduate
      university students. 30 asymptomatic students were randomly selected and
      preliminary examined: serum cholesterol, triglycerides, LDL and HDL were
      determined, 10.35% of the students had high cholesterol and triglycerides levels.
      It is an important finding offering a mass screening program in our undergraduate
      university students.

PMID- 16414855
TI  - A study on the analysis of ochratoxin-A in different poultry feed ingredients.
AB  - A study to assess ochratoxin content in different feed ingredients was conducted.
      Out of 156 samples of feed ingredients analyzed 36 were found contaminated with
      ochratoxin. The highest content was detected in maize (*84.4 microg/kg) while
      millet contained the minimum content (5 microg/kg). 120 samples i.e. 77% were
      found to be free of ochratoxin and 23% were contaminated. In the light of these
      results it is suggested that proper harvesting, storage of feed be done and
      unhygienic method of processing and production be avoided.

PMID- 16414856
TI  - Behavioral effects of 8-OH-DPAT in single and repeated haloperidol injected rats.
AB  - Haloperidol is an antipsychotic drug and shown to be antagonist at D2 receptors
      and found to cause severe impairment of locomotor performance. The serotonin
      (5HT1A) receptor agonist 8-OH-DPAT has been reported to attenuate extrapyramidal
      side effects of haloperidol. The present study was designed to examine the
      modulatory effect of serotonergic activities on haloperidol induced up-regulation
      of dopamine D2 receptors. In the acute phase of study, 8-OH-DPAT (0.5 mg/kg/ml)
      elicited behavioral syndrome was monitored in rats preinjected with haloperidol(5
      mg/kg/ml). Results of single haloperidol administration revealed that 8-OH-DPAT
      induced forepaw treading (p < 0.05) and hyperlocomotion (p < 0.01) were smaller
      in haloperidol than saline preinjected rats. In repeated phase of study, 8-OH
      DPAT (0.5 mg/kg/ml) induced behavioral syndrome was monitored in rats injected
      with haloperidol for 10 days (x2). The result of repeated haloperidol
      administration showed that 8-OH-DPAT elicited flat body posture (p < 0.01) was
      greater in repeated haloperidol injected rats than repeatedly saline injected
      rats. Relationship between 5HT1A receptors and D2 receptors has been discussed.
      It is suggested that combining neuroleptics with 5HT1A ligands is thought to
      improve the preclinical profile of neuroleptics and may be of interest in the
      development of new compounds that have greater therapeutic potential and/or
      better tolerated.

PMID- 16414857
TI  - Brine shrimp bioassay of Phoenix sylvestris.
AB  - Brine shrimp bioassay is a simple method for natural product research. The
      procedure determines LD50 values in microg/ml of active compound and extract in
      the brine medium. Three different extracts (methanol, chloroform and butanol) of
      the male flower inflorescence of Phoenix sylvestris were subjected to this
      bioassay. The results showed that the methanolic and butanolic extracts exhibit
      significant toxicity to the shrimps, while the chloroform extract was found to be
      non-toxic.

PMID- 16414858
TI  - Cephalosporin resistance and beta-lactamase production in clinical isolates of
      Staphylococcus aureus in Karachi.
AB  - WHO recommends surveillance program for monitoring antibiotic resistance. The
      present study is a step in this direction. More than 100 clinical isolates of
      Staphylococcus aureus were collected from different hospitals in Karachi and in
      vitro studies were carried out by Agar dilution method using different generation
      of cephalosporins. The result showed high resistance to majority of these
      antibiotics with increase in the MIC's while only ceftriaxone and ceftazidime
      were the most potent one showing significant antimicrobial activity. For the
      detection of beta-lactamase iodometric method was used which showed that 80%
      strains produced beta-lactamase which clearly depict the misuse of these agents.

PMID- 16414859
TI  - Comparative studies on nicotinic acid derivatives as hypolipoproteinemic agents.
AB  - Nicotinic acid and its related compounds are well known lipid lowering agents but
      the use of nicotinic acid in clinical practice is limited because of its side
      effects. To reduce the unwanted effects, new derivatives of nicotinic acid have
      been synthesized and tested in control and pathological animals for their
      antilipoproteinemic effects. Two newly synthesized derivatives of nicotinic acid
      i.e. 3-methoxy phenacyl nicotinium bromide (T1) and 2-methoxy phenacyl nicotinium
      bromide (T2) have been screened for their hypolipoproteinemic effects in white
      male rabbits. The compounds were administered in the doses of 30 mg/day and the
      results were compared with aspirin taken as the reference drug. The present work
      revealed that both of these synthesize compounds exhibited marked effects on
      plasma lipoproteins assuming that these compounds exerted their action by
      inhibiting hepatic production of very low density lipoprotins (VLDL), ultimately
      leading to reduction in low density lipoprotein. Clofibrate and aspirin are taken
      as standards to evaluate the potentials of these agents for their effects on
      lipid.

PMID- 16414860
TI  - Effect of dexamethasone on pituitary prolactin in the lizard Uromastix
      hardwickii.
AB  - The effect of 0.2-mg/ml dexamethasone (DXM) given intravenously to Uromastix
      hardwickii for 4 days; suppressed prolactin secretion by influencing the
      hypothalamus or para pituitary region. This effect of DXM through 30 min and 60
      min extracted pituitary suspensions also supported prolactin deficiencies through
      crop sac diametric response.

PMID- 16414861
TI  - Evaluation of Acetaminophen tablets by control test.
AB  - Various pharmacopoeial and non-pharmacopoeial control test applied to
      Acetaminophen tablets were used to evaluate for the uniformity of weight,
      diameter, thickness, medicaments, hardness and friability. The tests were
      intended to check the compliance of the prepared tablets with the accepted
      specifications.

PMID- 16414862
TI  - In vitro activity of ceftizoxime and ceftazidime in presence of essential and
      trace elements.
AB  - The research work comprises of the study of the changes in antimicrobial activity
      of ceftizoxime and ceftazidime after interaction with essential and trace
      elements. The minimum inhibitory concentration (MIC) was observed and thereafter
      compared with the standard MIC's of the respective drug by agar dilution method
      against both Gram positive and Gram-negative organisms so as to evaluate changes
      in antimicrobiological activity of the standard cephalosporins after metal
      interactions. It was observed that these metal elements that are essential for
      our body, either present within the body or coadminstered with vitamins markedly
      influence the MIC's of antibiotics by producing synergism or antagonism.

PMID- 16414863
TI  - Antibacterial studies of cefixime copper, zinc and cadmium complexes.
AB  - Antibacterial studies of metal complexes of cefixime, with copper zinc and
      cadmium have been carried out by observing the Minimum Inhibitory Concentration
      (MIC) and by measuring the Zone of Inhibition of the complexes and compared with
      the parent cephalosporin against both Gram negative and Gram positive
      microorganisms. Various microorganisms used were Staphylococcus aureus, E. coli,
      Klebsiella and Proteus species. For MIC observation, serial dilution method was
      employed and zone sizes were determined by diffusion disk method. Our
      investigations divulge that formation of complexes results in decrease in
      antimicrobial activity of cefixime and MIC values were increased.

PMID- 16414864
TI  - Antimicrobial activity of Penicillins in common paediatric infections.
AB  - Pediatric bacterial infections are very rapidly growing in developing countries.
      Bacterial resistance to antimicrobial agents is a serious problem in the
      treatment of Pediatric bacterial infection. One of the most effective ways to
      control antibiotic resistance, is the development of surveillance programs. For
      this purpose isolates were collected from paediatric wards of different
      hospitals. The result shows that isolates were highly resistant against majority
      of selected antibiotics with increase in the MIC's. In Penicillin group, the most
      effective agent is Amoxicillin and Clavulanic acid, more than 90% isolates of
      Staphylococcus aureus were susceptible while other agents, as Cloxacillin,
      Ampicillin and Amoxicillin alone shows moderate activity against Staphylococcus
      aureus and Escherichia coli.

PMID- 16414865
TI  - Bioactivity evaluation of Bergenia ciliata.
AB  - Bergenia ciliata was subjected to bioactivity analysis. The records of these
      investigations are described in this communication. A study made on the
      bioactivity analysis of medicinal herb Bergenia ciliata, which in folkloric
      medicine is used to cure hypoglycemic activity. A battery of assays was performed
      on different extracts of Bergenia ciliata which include hypoglycemic activities,
      toxic evaluations such as acute systemic and intracutaneous toxicity as well
      hemolysis test. Bergenia ciliata has been employed in folklore medicine to treat
      symptoms of diabetes mellitus. All the extracts except chloroform extract of root
      and leaves of Bergenia ciliata were found to possess hypoglycemic activity in
      Streptozotocin (STZ) treated rats. Therefore the plant can be classified as
      hypoglycemic, hypoglycemic activity in experimental diabetes ranging from 40-70%
      of its onset to reduce blood glucose level. The toxicological investigations of
      Bergenia ciliata with particular reference to acute systematic toxicity and
      intracutaneous toxicity in experimental animals displayed that it elicit severe
      toxicity. The symptoms of toxicity in intracutaneous test showed erythema and
      edema whereas assessment of acute systemic toxicity frequently observed breathing
      problem and initiations of diarrhea with blood in stool of experimental model and
      caused gastero-intestinal syndrome. Bergenia ciliata can produce toxicity
      suggesting a role in certain diseases. It is therefore, premature to speculate
      about mechanism of effect until toxin(s) is unequivocally identified. The
      hemolysis test on the extract of Bergenia ciliata was almost devoid of activity.

PMID- 16414866
TI  - Bioavailability study of tablet Bezafibrate 200 mg (Lipocor).
AB  - In order to determine the ultimate quality of any formulated dosage form and
      rationalize the therapeutic plan as well as to individualize the prescription, in
      vivo measurement of drug is the modem and specialized expertise of the
      clinical/research area of pharmacy practice, which provides effectiveness and
      assures the safety of drugs. All pharmacological, therapeutic or toxic responses
      are subject to reaching of drug at the site of action through connective tissue.
      Other than physico chemical properties of drug, there are numerous factors from
      manufacturing process to biochemical behaviour of the individual which resist in
      the absorption, distribution, metabolism and elimination of drugs in the
      biological system. Bezafibrate Tablet 200 mg (Lipocor) an oral conventional
      formulation manufactured by Efroze Chemical Industries (Pvt.) Ltd. was
      investigated for bioavailability followed by pharmacokinetic studies on adult,
      male, healthy, human local population. For this purpose, a sensitive, specific
      and validated method was used for the estimation of bezafibrate in blood. HPLC
      was performed on a reversed phase C18 column (flow rate 1.5 ml/min, UV = 230 nm)
      with 0.02 M buffer of KH2PO4 (Adjusted pH 3.5 with Phosphoric Acid) and Methanol
      (40: 60) whereas extraction of the drug from the plasma was carried out by
      deproteinization of plasma according to classical method described in previous
      studies (Obaid A. et al., 1999). Peak level (Tmax) of Bezafibrate Tablet 200 mg
      (Lipocor) was observed at about 1.42 +/- 0.53 hours after the dose and
      practically free Bezafibrate Tablet 200 mg (Lipocor) could be detected in blood
      after 9 hours. Cmax of the investigated formulation of Lipocor register mark or
      target was 1732 +/- 374.2 ng/ml. Area under curve (AUC) was 5198.65 +/- 1231.8
      ng. hr/ml.

PMID- 16414867
TI  - Clarithromycin synergism with essential and trace elements.
AB  - In order to ascertain the role of various essential and trace element
      complexation on the antibacterial activity of various macrolide antibiotics, the
      synergistic or antagonistic behavior of clarithromycin metal complexes has been
      studied and compared with the parent drug. Metal complexes of clarithromycin with
      magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and
      cadmium has been investigated for their antibacterial activity and compared with
      clarithromycin by observing the changes in minimum inhibitory concentration (MIC)
      and by measuring the zone of inhibition. of complexes against both gram negative
      and gram positive microorganisms. Various microorganisms used were Staphylococcus
      aureus, Streptococcus faecalis, Escherichia coli, Salmonella typhii, Proteus
      vulgaris, Shigella dysentary, Kelebcilla pneumoni and Staphylococcus epidermidis.
      For MIC observation, serial dilution method was employed and zone sizes were
      determined by diffusion disk method. Our investigations divulge that formation of
      clarithromycin complexes results in synergistic effect i.e., antimicrobial
      activity of complexes of clarithromycin increases with respect to parent
      clarithromycin drug and MIC of drug metal complexes decreased.

PMID- 16414868
TI  - Comparative evaluation of some new tranexamic acid derivatives and their copper
      (II) complexes for antitumor, analgesic, bactericidal and fungicidal activities.
AB  - The objective of this series of investigation was the synthesis and comparative
      evaluation of biological and pharmacological activities of some substitutive
      derivatives of Tranexamic Acid (T.A) and their copper (II) complexes. N
      Phthaloyltranexamic Acid (A-1), N-Acetyltranexamic Acid (A-2), Di-Tranexamate
      Diaquo Copper (II) (C-1) Di-N-Phthaloyltranexamate Diaquo Copper (II) (C-2) and
      Di-N-Acetyltranexamate Diaquo Copper (II) (C-3) were synthesized, using novel and
      reproducible procedures. These compounds were characterized by exploiting
      techniques such as FTIR, Mass Spectroscopy and FT 1H NMR. Bioactivities of the
      compounds were carried out and it was found that these compounds exhibited
      excellent anti-tumor, significant analgesic and antifungal activities.

PMID- 16414869
TI  - Development of theophylline sustained release dosage form based on Kollidon SR.
AB  - Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl
      acetate and povidone based matrix retarding polymer) were developed in this study
      in an attempt to design a dosage form that manifests desirable release profile
      and thorough adherence to official monographs. Four matrix tablet formulations
      were prepared by dry blending and direct compression of Kollidon SR and HPMC
      15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage
      of theophylline. Tablets containing only Kollidon SR with the active ingredient
      demonstrated a rapid rate of drug release with an initial burst effect.
      Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug
      with subsequent minimization of burst effect as confirmed by mean dissolution
      time, T50 and Higuchi release rate data. Among the batches containing HPMC-15
      cps, a direct relationship was obtained between release rate and the percentage
      of HPMC used. A suitable controlled release profile was obtained with the matrix
      tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed
      close resemblance to commercial products and compliance with USP specification.
      The results were explored and explained by the difference of physico-chemical
      property and hydration characteristics of the polymers. In addition to this
      result, the exponential model was applied to characterize the drug release
      behaviour from polymeric systems. It was found that, Fickian release is
      predominant in tablets containing Kollidon SR alone and non-Fickian mechanism
      plays an important role in the release of drug from HPMC containing tablets with
      a trend towards zero-order or case II release. In vitro release profile of two
      commercial brands were also undertaken for comparison and modulation of the
      experimental batches.

PMID- 16414870
TI  - Neurochemical effects of 8-hydroxy-2-di-n-propylamino tetralin in rats treated
      with haloperidol.
AB  - In view of a possible role of presynaptic serotonin (5-hydroxytryptamine, 5-HT)
      receptors in the precipitation of extrapyramidal side effects (EPS), the present
      study was designed to investigate the neurochemical effects of a selective 5-HT1A
      ligand, 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT) in rats following
      single (5 mg/kg) and repeated (two-times a day for 9 days at dosage of 5mg/kg)
      haloperidol administration. Haloperidol plus 8-OH-DPAT injected animals exhibited
      a decrease in dopamine (DA) and an increase in DA metabolite homovanillic acid
      (HVA) levels in the striatum and rest of the brain. The two groups of animals
      exhibited comparable levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid
      (5-HIAA) in the striatum and rest of the brain. Animals injected with haloperidol
      and killed 24 hrs after the last injection of haloperidol exhibited higher DA and
      HVA levels in the striatum but not in the rest of the brain. Conversely,
      dihydroxyphenylacetic acid (DOPAC), the other metabolite of DA, decreased in the
      rest of the brain. 5-HIAA concentrations increased in the striatum but not in the
      rest of the brain. Administration of 8-OH-DPAT significantly decreased 5-HT and 5
      HIAA levels in the rest of brain and did not alter 5-HIAA in the striatum of
      repeated saline injected rats. Conversely, same dose of 8-OH-DPAT injected to
      repeatedly haloperidol injected animals did not decrease 5-HT and 5-HIAA
      concentrations in the rest of the brain but decreased 5-HIAA levels in the
      striatum. No effect of 8-OH-DPAT injections occurred on striatal or rest of the
      brain DA metabolism in repeatedly saline injected animals except that DOPAC
      decreased in the striatum of both groups. The results are discussed in the
      context of a role of somatodendritic 5-HT1A receptors in the regulation of DA
      metabolism following single and repeated administration of haloperidol. It is
      suggested that an increase in the responsiveness of these receptors may be
      involved in the precipitation of EPS observed in patients on haloperidol therapy.

PMID- 16414871
TI  - Chemical constituents of Tagetes patula L.
AB  - Tagetes patula (Asteraceae) is a medicinal plant which is indigenous to Tropical
      America but cultivated in Pakistan. During the chemical study, conducted on the
      different parts of T. patula (roots, leaves and flowers) are found thiophenes,
      steroidal and terpenoidal type of constituents. Their structures were
      characterized by different spectroscopic. Among the thiophenes triterpens and
      steroids are two thiophenes, one triterpene and one steroid first time isolated
      from the genes Tegetes methods.

PMID- 16414872
TI  - Comparative antimicrobial evaluation of Cephalosporins and Quinolones in common
      paediatric infections.
AB  - More than 90% of world's children are born each year in the developing world.
      Each year 12.9 million children die. Twenty eight percent of death are caused by
      pneumonia, 23% by diarrheal disease and 16% by vaccine-preventable diseases.
      Thirty-five thousand die each day, most from common and preventable problems.
      Health and illness are the result of a complex dynamic of environmental, social,
      political and economic factors. Bacterial resistance to antimicrobial agents is a
      continuing serious problem in the treatment of infections. Although this problem
      was recognized shortly after the commercial introduction of antimicrobial agents,
      it means that resistance is now emerging at a more rapid rate than ever before.
      To start with, during the present study an effort has been made to accomplish
      this task, 84 clinical isolates of Staphylococcus aureus, Escherichia coli and
      Pseudomonas aeruginosa were collected from different hospitals in Karachi. An in
      vitro study of these isolates was carried out by Agar dilution method using
      eleven antimicrobial agents and their combination (Lorian, 1991). Among
      Cephalosporins, third generation Cephalosporin, Cefotaxime was highly effective
      against Gram positive and Gram negative bacteria. Cefotaxime was active against
      Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. 1.19%
      isolates of Staphylococcus aureus, 19% isolates of Escherichia coli and 10%
      isolates of Pseudomonas aeruginosa were resistant against Cefotaxime. In
      Quinolone group, Ofloxacin was highly active against Staphylococcus aureus,
      Escherichia coli and Pseudomonas aeruginosa. Whereas 28% isolates of
      Staphylococcus aureus, 26% isolates of Escherichia coli and 11% isolates of
      Pseudomonas aeruginosa were resistant to Ofloxacin. Twenty six percent isolates
      of Staphylococcus aureus and 58% isolates Escherichia coli were resistant against
      Ciprofloxacin.

PMID- 16414873
TI  - Evaluation of antibacterial activity of Bergenia ciliata.
AB  - Bergenia ciliata was subjected to antibacterial analysis. A battery of assays
      were performed on different extracts of Bergenia ciliata for antibacterial
      activities. Antibacterial effects of ethanol, hexane, ethyl acetate, chloroform,
      butanol and aqueous extracts of the roots and leaves extract of Bergenia ciliata
      exhibited various degree of inhibition activity. It was observed that root and
      leaves extract were promising against gram positive and gram negative bacteria
      viz. Bacillus subtilis, Bacillus megaterium and Pseudomonas aeruginosa. This
      study showed that Bergenia ciliata could inhibit selectively bacteria.

PMID- 16414874
TI  - Fermentative production of L-lysine: fungal fermentation and mutagenesis-II: a
      review.
AB  - Lysine has been recognized as one of the most deficient essential amino acids. It
      is an economically important food and feed supplement. It has also got various
      pharmaceutical applications in the formulation of diets with balanced amino acid
      concentration and in amino acid infusions. Chemical, enzymatic and fermentation
      processes have been used to synthesize lysine. The objective of this review is to
      outline the research work of various scientists which provide important and
      beneficial information regarding the production of lysine through fungal
      fermentation and mutagenesis. Moreover, methods to improve the total yield and
      quality of lysine are also presented.

PMID- 16414875
TI  - Hypoprolactinemia following intradermal administration of ouabain in Uromastix
      hardwickii.
AB  - A variety of drugs can alter the secretion of prolactin (PRL) by the pituitary
      gland in most animals. Secretion of prolactin is predominantly, under negative
      control of hypothalamus, and in this respect, it is unique among the pituitary
      hormones. This study was undertaken to evaluate the crop-sac diameterical
      response to ouabain treated Uromastix pituitary suspension. 0.1 ml suspension of
      ouabain treated Uromastix pituitary gave a minimum diametric crop-sac response of
      0.85 cm and a maximum of 0.95 cm. Data indicates that oubain promotes the
      secretion of prolactin inhibiting hormone (PRIH), and produces hypoprolactinemia.

PMID- 16414876
TI  - In vitro activity of cefazoline and cefuroxime in presence of essential and trace
      elements.
AB  - Present research focuses to evaluate changes in antimicrobial activity of
      cefazolin sodium and cefuroxime after interactions with essential and trace
      elements. The minimum inhibitory concentration (MIC) was observed and
      subsequently compared with the standard MIC's of the respective drug by agar
      dilution method against a variety of Gram positive and Gram negative organisms.
      It was observed that these metal elements are essential for our body, either
      present within the body or co-administered with vitamins or otherwise, markedly
      influence the MIC's of antibiotics by producing synergism or antagonism.

PMID- 16414877
TI  - Method development for analysis of gliclazide in human plasma by using high
      performance liquid chromatography.
AB  - Since 1970, dissolution requirements have been included in tablets and capsules
      monographs, in general, in response to concerns for bioavailability of equal
      significance is the recognition of the immense value of dissolution testing as a
      tool for quality control. Thus, equivalence in dissolution behaviour was sought
      in the light of both bioavailability and quality control considerations (Coppack
      et al., 1990). Nonetheless, dissolution profiles are often considered by the
      industry to ascertain the release rates of drug from tablet formulations as a
      quality assurance tool. However, in terms of sensitivity, precision and
      specificity, high-performance liquid chromatographic (HPLC) method may offer
      additional advantages (Charles & Ravenscroft, 1984 and Nawaz, 2001).

PMID- 16414878
TI  - Resistance pattern of different aminoglycosides against Gram positive and Gram
      negative clinical isolates of Karachi.
AB  - Microbial resistance to majority of the available antimicrobial agent is a
      serious and global problem. Due to heavy and discriminate usage of antibiotics,
      high prevalence of drug-resistant bacteria in the indigenous fecal flora, poor
      standards of sanitation, lack of education and prevalence of malnutrition. This
      problem is at its extreme in developing countries like Pakistan. For this various
      Aminoglycosides were tested against different Gram positive and Gram negative
      isolates. The results showed that these isolates were resistant against most of
      these antibiotics with increase in MIC's. In Aminoglycoside group Tobramycin was
      the most effective agent against Staph. aureus and E. coli with MIC90s of 1
      microg/ml and 2 microg/ml, while against Klebsiella and P. aeruginosa its
      activity was moderate to low. Amikacin showed highest activity against P.
      aeruginosa, E. coli and Klebsiella species with MIC90s of 4 microg/ml and 8
      microg/ml. Kanamycin and Streptomycin were not active against the tested
      isolates.

PMID- 16414879
TI  - Synthesis and characterization of copper(I) triphenylphosphine complexes with
      ethylpyridine.
AB  - Copper(I) complexes of the type [CuX(PPh3)n(L)n]n {where X = Cl-, Br- I-, NO3,
      SCN-; PPh3 = triphenylphosphine and L = 4-ethylpyridine} have been prepared and
      characterized on the basis of their molecular weight, magnetic susceptibility,
      conductance, infrared studies and elemental analysis. Ethylpyridine behaved as
      monodentate ligand. The variation in stoichiometry and the probable structures of
      these complexes have been discussed.

PMID- 16414880
TI  - MHD waves and oscillations in the solar plasma. Introduction.
AB  - The Sun's magnetic field is responsible for many spectacularly dynamic and
      intricate phenomena, such as the 11 year solar activity cycle, the hot and
      tenuous outer atmosphere called the solar corona, and the continuously expanding
      stream of solar particles known as the solar wind.Recently, there has been an
      enormous increase in our understanding of the role of solar magnetism in
      producing the observed complex atmosphere of the Sun. One such advance has
      occurred in the detection, by several different high-resolution space instruments
      on-board the Solar and Heliospheric Observatory and Transition Region and Coronal
      Explorer satellites, of magnetic waves and oscillations in the solar corona. The
      new subjects of solar atmospheric and coronal seismology are undergoing rapid
      development. The aim of this Scientific Discussion Meeting was to address the
      progress made through observational, theoretical and numerical studies of wave
      phenomena in the magnetic solar plasma. Major theoretical and observational
      advances were reported by a wide range of international scientists and pioneers
      in this field, followed by lively discussions and poster sessions on the many
      intriguing questions raised by the new results. Theoretical and observational
      aspects of magnetohydrodynamic waves and oscillations in general, and how these
      wave phenomena differ in various regions of the Sun, including sunspots, the
      transient lower atmosphere and the corona (in magnetic loops, plumes and
      prominences), were addressed through invited review papers and selected poster
      presentations. The results of these deliberations are collected together in this
      volume.

PMID- 16414881
TI  - Magnetohelioseismology.
AB  - The helioseismic investigation of the solar interior to elucidate the behaviour
      of the Sun's magnetic field and the interior's role in the solar interior is
      considered. Such study may be called magnetohelioseismology (from the Greek roots
      magnetis, helios and seismos).

PMID- 16414883
TI  - Dispersion relations, rays and ray splitting in magnetohelioseismology.
AB  - Local helioseismology seeks to probe the near surface regions of the Sun, and in
      particular of active regions. These are distinguished by their strong magnetic
      fields, yet current local techniques do not take proper account of this. Here, we
      first derive appropriate gravito-magneto-acoustic dispersion relations, and then
      use these to examine how acoustic rays entering regions of strong field split
      into fast and slow components, and the subsequent fates of each. Specifically,
      two types of transmission point, where wave energy can transfer from the fast to
      slow branch (or vice versa) are identified; one close to the equipartition level
      where the sound and Alfven speeds coincide, and one higher up near the acoustic
      cutoff turning point. This second type only exists for rays of low frequency or
      low l though. In accord with recent studies of fast-to-slow mode conversion from
      the perspective of p-modes, magnetic field inclination is found to have
      significant consequences for wave splitting.

PMID- 16414882
TI  - Observational aspects of sunspot oscillations.
AB  - Oscillatory phenomena observed in sunspot umbrae and penumbrae are reviewed and
      critically discussed. A natural interplay between the thermal atmospheric
      stratification and the ordered collimation imposed by the intense magnetic field
      leads naturally to the characteristic properties of the umbral chromospheric and
      photospheric oscillations and their interpretation as low-beta (beta = 8pip/B2)
      slow magneto-acoustic-gravity waves guided along the ambient magnetic field.

PMID- 16414884
TI  - Magnetic coupling of waves and oscillations in the lower solar atmosphere: can
      the tail wag the dog?
AB  - Can the ubiquitously magnetic solar atmosphere have any effect on solar global
      oscillations? Traditionally, solar atmospheric magnetic fields are considered to
      be somewhat less important for the existence and characteristic features of solar
      global oscillations (p,f and the not-yet-observed g-modes). In this paper, I
      demonstrate the importance of the presence of magnetism and plasma dynamics for
      global resonant oscillations in the solar atmosphere. In particular, in the lower
      part of the solar atmosphere there are both coherent and random components of
      magnetic fields and velocity fields, each of which contribute on its own to the
      line widths and frequency variations of solar global acoustic waves. Changes in
      the coherent large-scale atmospheric magnetic fields cause frequency shifts of
      global oscillations over a solar cycle. The random character of the continuously
      emerging, more localized, magnetic carpet (i.e. small-scale, possibly even sub
      resolution, loops) gives rise to additional frequency shifts. On the other hand,
      random and organized surface and sub-surface flows, like surface granulation,
      meridional flows or differential rotation, also affect the coupling mechanism of
      global oscillations to the lower magnetic atmosphere. The competition between
      magnetic fields and flows is inevitable. Finally, I shall discuss how solar
      global oscillations can resonantly interact with the overlaying inhomogeneous
      lower solar atmosphere embedded in a magnetic carpet. Line width broadening and
      distorsion of global acoustic modes will be discussed. The latter is suggested to
      be tested and measured by using ring-analysis techniques.

PMID- 16414885
TI  - The nature of moss and lower atmospheric seismology.
AB  - The discovery of so-called solar 'moss', i.e. dynamic and bright upper transition
      region emission at chromospheric heights above active region plage, provides a
      novel diagnostic to probe the structure, dynamics, energetics and coupling of the
      magnetized solar chromosphere and transition region. We briefly review
      observations of the morphology and connectivity in the low solar atmosphere, with
      a particular focus on the propagation of oscillations and waves in the moss. We
      also present recent work that combines moss observations and numerical modelling,
      and which sheds light on the (quasi-periodic) formation of dynamic jets
      (spicules), and the propagation of normally evanescent oscillations into the
      corona. We also briefly explore how coronal oscillations could be exploited to
      determine the connectivity between photosphere and corona, i.e. perform
      seismology of the lower solar atmosphere.

PMID- 16414886
TI  - Numerical modelling of MHD waves in the solar chromosphere.
AB  - Acoustic waves are generated by the convective motions in the solar convection
      zone. When propagating upwards into the chromosphere they reach the height where
      the sound speed equals the Alfven speed and they undergo mode conversion,
      refraction and reflection. We use numerical simulations to study these processes
      in realistic configurations where the wavelength of the waves is similar to the
      length scales of the magnetic field. Even though this regime is outside the
      validity of previous analytic studies or studies using ray-tracing theory, we
      show that some of their basic results remain valid: the critical quantity for
      mode conversion is the angle between the magnetic field and the k-vector: the
      attack angle. At angles smaller than 30 degrees much of the acoustic, fast mode
      from the photosphere is transmitted as an acoustic, slow mode propagating along
      the field lines. At larger angles, most of the energy is refracted/reflected and
      returns as a fast mode creating an interference pattern between the upward and
      downward propagating waves. In three-dimensions, this interference between waves
      at small angles creates patterns with large horizontal phase speeds, especially
      close to magnetic field concentrations. When damping from shock dissipation and
      radiation is taken into account, the waves in the low-mid chromosphere have
      mostly the character of upward propagating acoustic waves and it is only close to
      the reflecting layer we get similar amplitudes for the upward propagating and
      refracted/reflected waves. The oscillatory power is suppressed in magnetic field
      concentrations and enhanced in ring-formed patterns around them. The complex
      interference patterns caused by mode-conversion, refraction and reflection, even
      with simple incident waves and in simple magnetic field geometries, make direct
      inversion of observables exceedingly difficult. In a dynamic chromosphere it is
      doubtful if the determination of mean quantities is even meaningful.

PMID- 16414887
TI  - Recent progress in prominence seismology.
AB  - Prominence seismology is a rapidly developing topic which seeks to infer the
      internal structure and properties of solar prominences from the study of their
      oscillations. An extense observational background about oscillations in quiescent
      solar prominences has been gathered during the last 70 years. These observations
      point out the existence of two different types of oscillations: flare-induced
      oscillations (winking filaments) which affect the whole prominence and are of
      large amplitude and small amplitude oscillations which seem to be of local
      nature. From the theoretical point of view, few models have been set up to
      explain the phenomenon of winking filaments while, on the contrary, for small
      amplitude oscillations a large number of models trying to explain the observed
      features have been proposed. Here, recent theoretical and observational
      developments on both types of oscillations are reviewed, and suggestions about
      future research topics which should provide us with a more in-depth knowledge of
      solar prominences are made.

PMID- 16414888
TI  - Coronal magnetohydrodynamic waves and oscillations: observations and quests.
AB  - Coronal seismology, a new field of solar physics that emerged over the last 5
      years, provides unique information on basic physical properties of the solar
      corona. The inhomogeneous coronal plasma supports a variety of
      magnetohydrodynamics (MHD) wave modes, which manifest themselves as standing
      waves (MHD oscillations) and propagating waves. Here, we briefly review the
      physical properties of observed MHD oscillations and waves, including fast kink
      modes, fast sausage modes, slow (acoustic) modes, torsional modes, their
      diagnostics of the coronal magnetic field, and their physical damping mechanisms.
      We discuss the excitation mechanisms of coronal MHD oscillations and waves: the
      origin of the exciter, exciter propagation, and excitation in magnetic
      reconnection outflow regions. Finally, we consider the role of coronal MHD
      oscillations and waves for coronal heating, the detectability of various MHD wave
      types, and we estimate the energies carried in the observed MHD waves and
      oscillations: Alfvenic MHD waves could potentially provide sufficient energy to
      sustain coronal heating, while acoustic MHD waves fall far short of the required
      coronal heating rates.

PMID- 16414889
TI  - Damping of magnetohydrodynamic waves by resonant absorption in the solar
      atmosphere.
AB  - In the last decade we have been overwhelmed by an avalanche of discoveries of
      magnetohydrodynamic (MHD) waves by the Solar and Heliospheric Observatory and
      Transition Region and Coronal Explorer observatories. Both standing and
      propagating versions of fast magnetoacoustic and slow magnetoacoustic MHD waves
      have been detected. Information on the damping times and damping distances of
      these waves is less detailed and less accurate than that on periods and
      amplitudes. Nevertheless, observations show the damping times and damping lengths
      are often short. Also, different types of MHD waves in different types of
      magnetic structures likely require different damping mechanisms. The phenomenon
      of fast damping is well documented for the standing fast magnetosonic kink waves
      in coronal loops. This paper concentrates on standing fast magnetosonic waves. It
      reports on results on periods and damping times due to resonant absorption in one
      dimensional and two-dimensional models of coronal loops. Special attention is
      given to multiple modes.

PMID- 16414890
TI  - Slow magnetohydrodynamic waves in the solar atmosphere.
AB  - There is increasingly strong observational evidence that slow magnetoacoustic
      modes arise in the solar atmosphere, either as propagating or standing waves.
      Sunspots, coronal plumes and coronal loops all appear to support slow modes. Here
      we examine theoretically how the slow mode may be extracted from the
      magnetohydrodynamic equations, considering the special case of a vertical
      magnetic field in a stratified medium: the slow mode is described by the Klein
      Gordon equation. We consider its application to recent observations of slow waves
      in coronal loops.

PMID- 16414891
TI  - Propagating magnetohydrodynamics waves in coronal loops.
AB  - High cadence Transition Region and Coronal Explorer (TRACE) observations show
      that outward propagating intensity disturbances are a common feature in large,
      quiescent coronal loops, close to active regions. An overview is given of
      measured parameters of such longitudinal oscillations in coronal loops. The
      observed oscillations are interpreted as propagating slow magnetoacoustic waves
      and are unlikely to be flare-driven. A strong correlation, between the loop
      position and the periodicity of the oscillations, provides evidence that the
      underlying oscillations can propagate through the transition region and into the
      corona. Both a one- and a two-dimensional theoretical model of slow
      magnetoacoustic waves are presented to explain the very short observed damping
      lengths. The results of these numerical simulations are compared with the TRACE
      observations and show that a combination of the area divergence and thermal
      conduction agrees well with the observed amplitude decay. Additionally, the
      usefulness of wavelet analysis is discussed, showing that care has to be taken
      when interpreting the results of wavelet analysis, and a good knowledge of all
      possible factors that might influence or distort the results is a necessity.

PMID- 16414892
TI  - Magnetohydrodynamic waves in coronal polar plumes.
AB  - Polar plumes are cool, dense, linear, magnetically open structures that arise
      from predominantly unipolar magnetic footpoints in the solar polar coronal holes.
      As the Alfven speed is decreased in plumes in comparison with the surrounding
      medium, these structures are natural waveguides for fast and slow magnetoacoustic
      waves. The simplicity of the geometry of polar plumes makes them an ideal test
      ground for the study of magnetohydrodynamic (MHD) wave interaction with solar
      coronal structures. The review covers recent observational findings of
      compressible and incompressible waves in polar plumes with imaging and spectral
      instruments, and interpretation of the waves in terms of MHD theory.

PMID- 16414893
TI  - Nonlinear waves in the solar atmosphere.
AB  - In this paper, we give a brief review of the contemporary theory of nonlinear
      waves in the solar atmosphere. The choice of topics reflects personal interests
      of the author. Historically the theory of nonlinear waves was first applied to
      the solar atmosphere to explain the chromospheric and coronal heating. It was
      assumed that the turbulent motion in the solar convective zone excites sound
      waves that propagate upwards. Due to nonlinearity these waves steepen and form
      shocks. The wave energy dissipates in these shocks thus heating the corona. We
      give a brief description of propagation and damping of nonlinear sound waves in
      the stratified solar atmosphere, and point out that, at present, the acoustic
      heating remains the most popular theory of heating the lower chromosphere. Then
      we extend the analysis to nonlinear slow magnetosonic waves in coronal plumes and
      loops, and discuss its implications for interpretation of observational results.
      The next topic of interest is the propagation of nonlinear waves in a
      magnetically structured atmosphere. Here, we restrict our analysis to slow
      sausage waves in magnetic tubes and discuss properties of solitary waves
      described by the Leibovich-Roberts equation. We conclude with the discussion of
      nonlinear theory of slow resonant layers, and its possible application to
      helioseismology.

PMID- 16414894
TI  - Drivers of the solar wind: then and now.
AB  - Early spacecraft data in the 1960s revealed solar wind properties, which could
      not be well explained by models in which the electron pressure gradient was the
      principal accelerating force. The Alfven waves discovered around 1970 were
      thought for a while to provide additional energy and momentum, but they
      ultimately failed to explain the rapid acceleration of the fast wind close to the
      Sun. By the late 1970s, various data were suggesting the importance of the ion
      cyclotron resonance far from the Sun. This notion was soon applied to the
      acceleration region close to the Sun. The models, which resulted, suggested that
      the fast wind could be driven mainly by the proton pressure gradient. Since the
      mid-1990s, Solar and Heliospheric Observatory has provided remarkable data, which
      have verified some of the predictions of these theories, and given impetus to
      studies of the ion-cyclotron resonance as the principal mechanism for heating the
      coronal holes, and ultimately driving the fast wind. After a historical review,
      we discuss the basic ideas behind current research, emphasizing the particle
      kinetics. We discuss remaining problems, especially the source of the ion
      cyclotron resonant waves.

PMID- 16414895
TI  - Quasi-mode damping in two-dimensional fully non-uniform coronal loops.
AB  - Resonantly damped fast kink quasi-modes are computed in fully resistive
      magnetohydrodynamics for fully non-uniform two-dimensional equilibrium models.
      The equilibrium model is a straight cylindrically symmetric flux tube with a
      plasma density that is non-uniform both across and along the loop. The variation
      of density across the loop can cover the whole loop. Our results indicate that
      the period and damping of coronal loop oscillations mainly depend on the density
      contrast and the inhomogeneity length-scale and are independent of the details of
      longitudinal stratification. This study extends previous studies on coronal loop
      oscillations, and allows for a better comparison between observations and theory.

PMID- 16414896
TI  - Alfvenic-turbulence-heated magnetic loops: effects of lateral expansion and
      magnetic twist.
AB  - Using a 1.5-dimensional two-fluid magnetic loop model in which loops are heated
      by Alfvenic turbulence, we explore the effects on the loop parameters of the
      varying cross-section and the magnetic twist. The introduced magnetic twist is
      set to be around the kink instability threshold for a curved loop. It is found
      that: (i) The lateral expansion, which takes place close to footpoints, can
      significantly influence the heating profile, leading to a significant footpoint
      plasma flow. When observed on disc, the corresponding footpoint blue/red shift
      may be found for upper transition region lines. (ii) The effects introduced by
      magnetic twist are twofold. Firstly, the twist-related force may contribute to
      the axial force balance. Secondly, the projection effect reduces the electron and
      proton thermal conductivities. The former is found to be of little significance;
      however, the latter gives rise to considerable changes compared to the untwisted
      case.

PMID- 16414897
TI  - Coronal waves: propagation in the multi-fluid description.
AB  - We study wave propagation in the low-beta coronal plasma using a collisionless
      multi-fluid model. Neglecting the electron inertia, this model allows us to take
      into account ion-cyclotron wave effects that are absent in the
      magnetohydrodynamics model. To accomplish this, we perform a Fourier plane-wave
      perturbation analysis. Solving numerically the dispersion relations obtained from
      a two- and three-fluid model, dispersion curves for representative parameters of
      the solar corona are presented. The results reveal the presence of resonance
      frequencies that might play a role in coronal heating.

PMID- 16414898
TI  - Solar atmospheric magnetic effects on global acoustic and atmospheric gravity
      eigenoscillations.
AB  - Solar global observations suggest that the frequency and the line width of
      helioseismic acoustic eigenmodes vary with the solar cycle. One reason for the
      measured changes could be the variation of the global atmospheric magnetic
      fields. We model global solar oscillations in a plane-parallel, three-layer model
      within the framework of linear dissipative magnetohydrodynamics, and study the
      effects of a homogenous, horizontal atmospheric magnetic field on global
      oscillations. We find magnetoacoustic f- and p-modes and also atmospheric gravity
      modes (g-modes) among the eigenoscillations of the system. We conclude that
      changes in the atmospheric magnetic field can, significantly, shift the
      frequencies and vary the line width of global oscillation modes.

PMID- 16414899
TI  - Excitation and damping of disturbances in cylindrical coronal loops.
AB  - The excitation and damping of transversal coronal loop oscillations is studied
      using one-and two-dimensional models of line-tied cylindrical loops. By solving
      the time-dependent magnetohydrodynamic equations it is shown how an initial
      disturbance generated in the solar corona induces kink mode oscillations. We
      investigate the effect of the disturbance on a loop with a non-uniform boundary
      layer. In particular, a strong damping of transversal oscillations due to
      resonant absorption is found, such as predicted by previous works based on normal
      mode analysis.

PMID- 16414902
TI  - Cellulite: Is there a role for injectables?
AB  - BACKGROUND: Cellulite describes the cutaneous dimpling of the thighs, buttocks,
      and hips that is seen predominately in women. Current evidence suggests that
      structural differences in fat architecture between the sexes account for its
      appearance. Mesotherapy, a method of delivering medication locally with the use
      of numerous cutaneous injections, has recently become a popular method to
      purportedly treat the condition. METHODS: An overview of cellulite and adipocyte
      physiology, with a literature review and appraisal of compounds commonly used in
      mesotherapy. RESULTS: Experimental studies using individual mesotherapy
      ingredients for other conditions suggest a number of mechanisms, including
      lipolysis, disrupting connective tissue and augmenting circulation, which may
      theoretically improve cellulite. Peer-reviewed studies have not evaluated whether
      these effects translate clinically. CONCLUSIONS: Until further studies are
      performed, patients considering mesotherapy for cellulite must be aware that the
      substances currently being injected to treat this cosmetically disturbing, but
      medically benign, condition have not been thoroughly evaluated for safety or
      efficacy.

PMID- 16414903
TI  - Pilot study to determine the efficacy of ALA-PDT photo-rejuvenation for the
      treatment of facial ageing.
AB  - OBJECTIVE: The study was divided into two parts. The objective of the preliminary
      study was to evaluate the optimum dose and tolerance of 5-aminolaevulinic acid (5
      ALA) compared to a placebo cream with a 633-nm LED light in normal, healthy,
      volunteer forearm skin. The second study was to establish if ALA-PDT treatments
      improve the signs of ageing. RESULTS: Threshold photosensitization was observed
      using 5% 5-ALA under plastic occlusion for 30 minutes following a dose response
      study of forearm skin. Mild improvement was observed, using this concentration
      and time, for periorbital skin aging. Other anecdotal positive results of photo
      rejuvenation are reported for facial and chest areas.

PMID- 16414904
TI  - The utilization of nonthermal blue (405-425 nm) and near infrared (850-890 nm)
      light in aesthetic dermatology and surgery-a multicenter study.
AB  - BACKGROUND: A major cause of skin aging is a chronic micro-inflammation triggered
      by UV radiation and external pollutants. It has been demonstrated that blue light
      diminishes inflammatory conditions and near infrared light enhances circulation.
      OBJECTIVES: To assess the effectiveness of a non thermal dual wavelength -- blue
      (405 - 420 nm) and near infrared (850 - 900 nm) -- light source in skin
      rejuvenation, in the reduction of the duration of post skin resurfacing erythema
      and in the acceleration of healing of post surgical conditions (face lift and
      breast augmentation). METHODS: We have utilized a non contact, hand free dual
      wavelength light source (iClearXL and Clear100XL, Curelight Ltd) to treat over 60
      patients and perform three controlled studies in four centers. Follow up duration
      was three months. Control group for photo-rejuvenation consisted of patients
      treated with Glycolic peeling and daily appliance of vitamin C Control group for
      post skin resurfacing erythema duration consisted of patients untreated by the
      light source and control group for post surgical healing consisted of patients
      untreated by the light source or treated by the light source on one side only.
      RESULTS: Post skin resurfacing erythema duration is reduced by 90%. The healing
      of post surgical conditions is substantially accelerated and discomfort is
      reduced. The anti aging effect of the light source includes: reduction of pore
      size in 90% of patients with stable results at three months follow up, enhanced
      skin radiance in 90% of patients with stable results at three months follow up
      and smoothing of fine wrinkles in 45% of patients with stable results at three
      months follow up. The control group showed poor results which were stable for a
      duration of less than one month. CONCLUSIONS: A non thermal, non contact / hand
      free light source emitting at 405-420 nm and 850-900 nm considerably enhances
      aesthetic and surgical aesthetic procedures without consuming user time.

PMID- 16414905
TI  - Adverse reactions to dermal fillers: a review of European experiences.
AB  - BACKGROUND: In Europe, numerous dermal fillers have been utilized for the past
      decade. A lot of drawbacks have been reported and sometimes, severe complications
      occurred. OBJECTIVE: Our purpose is to report the clinical aspects of the adverse
      reactions following injections of some of the dermal fillers. Histological
      aspects of complications are also described. RESULTS: Adverse reactions secondary
      to biodegradable products are usually time limited, but with the non
      biodegradable products, we have observed severe, persistent, and recurrent
      complications. Histological examinations, in cases of non-biodegradable products,
      may show the presence and persistence of the filler. CONCLUSION: For the moment,
      there is no ideal dermal filler. All fillers can lead to adverse events and we
      need to inform patients fully before injecting. Clinical studies with long-term
      follow-up before launching a new product on the market are recommended. We
      believe that in Europe, at present, the CE mark is not a guarantee of safety of
      dermal fillers.

PMID- 16414906
TI  - Optimising the design of a broad-band light source for the treatment of skin.
AB  - Phototherapy has become a treatment of choice in many areas of medicine. Light
      can be used to deliver energy to tissue selectively targeting specific structures
      in order to induce the desired therapeutic outcome. The choice of optical
      parameters for a specific application is not simple. Wavelength, energy, exposure
      time and fluence can be varied and induce a wide range of tissue effects. The
      treatment of the skin with light is probably the one phototherapy application
      that is most developed in terms of technology and market maturity. White light
      systems are extensively used to address a range of skin conditions. However,
      different conditions have different physiology and hence require differing
      optical parameters. The technology standard is based upon systems, which have a
      number of different optical filters allowing the output to be tailored to the
      specific application. This paper discusses the advantages of a different type of
      system, namely the iPulse i300 (Cyden Ltd, Swansea, UK), which uses a single
      dichroic reflectance filter and whose optical output is changed by varying other
      parameters in a carefully controlled manner.

PMID- 16414907
TI  - The lamellar peel: a sequential nonablative and ablative laser treatment for
      facial skin rejuvenation.
AB  - OBJECTIVES: Ablative and nonablative laser treatments have established themselves
      independently in the rejuvenation of aging skin. This study was designed to
      determine the effects of sequential nonablative and ablative laser treatments on
      facial skin. MATERIALS AND METHODS: Twelve patients, ages 32-56 years, with skin
      phototypes I-IV, received three treatments spaced six weeks apart. Each treatment
      consisted of one pass with 1319-nm Nd:YAG laser at 16 J/cm(2), 50 ms pulse
      duration. This was immediately followed by one pass of 2940-nm Er:YAG laser at 5
      J/cm(2). Photographs and biopsies were taken prior to the first treatment and
      following the third treatment. RESULTS: Clinical improvements in facial skin tone
      and texture, acne scarring and dyschromia were noted in all patients. Histologic
      changes included a more compact epidermal granular layer and lamellar collagen
      formation with decreased solar elastosis in the dermis. Compared to controls,
      treated skin had a thicker, more homogeneous papillary dermis. CONCLUSION: The
      sequential use of nonablative and superficial ablative laser treatments
      clinically and histologically improved photodamaged and chronologically aged
      skin. This occurred with minimal recovery and little morbidity, demonstrating
      this laser application to be a safe and effective method for facial rejuvenation.

PMID- 16414908
TI  - A study to determine the efficacy of combination LED light therapy (633 nm and
      830 nm) in facial skin rejuvenation.
AB  - BACKGROUND: The use of visible or near infrared spectral light alone for the
      purpose of skin rejuvenation has been previously reported. A method of light
      emitting diode (LED) photo rejuvenation incorporating a combination of these
      wavelengths and thus compounding their distinct stimulation of cellular
      components is proposed.Objective. To assess the efficacy and local tolerability
      of combination light therapy in photo rejuvenation of facial skin. METHODS:
      Thirty-one subjects with facial rhytids received nine light therapy treatments
      using the Omnilux LED system. The treatments combined wavelengths of 633 nm and
      830 nm with fluences of 126 J/cm(2) and 66 J/cm(2) respectively. Improvements to
      the skin surface were evaluated at weeks 9 and 12 by profilometry performed on
      periorbital casts. Additional outcome measures included assessments of clinical
      photography and patient satisfaction scores. RESULTS: Key profilometry results
      Sq, Sa, Sp and St showed significant differences at week 12 follow-up; 52% of
      subjects showed a 25%-50% improvement in photoaging scores by week 12; 81% of
      subjects reported a significant improvement in periorbital wrinkles on completion
      of follow-up. CONCLUSION: Omnilux combination red and near infrared LED therapy
      represents an effective and acceptable method of photo rejuvenation. Further
      study to optimize the parameters of treatment is required.

PMID- 16414909
TI  - Safety of Sculptra: a review of clinical trial data.
AB  - The development of facial lipoatrophy as a result of highly active antiretroviral
      therapy (HAART) used to treat patients with human immunodeficiency virus (HIV)
      has adversely affected patient quality of life and compliance with therapy.
      Thanks to modern pharmacotherapies, HIV can now be viewed as a chronic disease;
      however, this welcome change has exacerbated the effect of facial lipoatrophy
      since HIV-infected patients can now expect to live longer and healthier lives but
      remain subject to public scrutiny of their ongoing disease state. Sculptra
      (Dermik Laboratories, Berwyn, PA, USA) has recently been introduced in the USA
      for correction of the appearance of facial lipoatrophy. The device affords long
      lasting restoration while still being non-permanent, thus providing an extended
      but adjustable cosmetic effect. The safety profile of this product has been
      observed in four investigator-initiated clinical trials of more than 250 HIV
      patients and in numerous investigator reports, with no serious adverse events or
      infections deemed associated with the product. Maintenance of the excellent
      safety profile for this injectable device requires adherence to a novel technique
      and appreciation of its unique attributes.

PMID- 16414910
TI  - Comparison of two wound dressings after laser skin resurfacing.
AB  - BACKGROUND: It has been reported that the final outcome of laser resurfacing
      still depends to a large degree on the efficiency of the post laser resurfacing
      wound care in promoting wound healing and preventing early and late
      complications. OBJECTIVE: The objective of this study was to evaluate and compare
      a new hydrocolloid dressing, H2460, with Flexzan(TM) for healing of an acute
      wound after laser skin resurfacing (LSR). METHODS: Ten volunteers received LSR of
      the peri-orbital area with an erbium:YAG laser. Identical parameters were used on
      both sides: 2 J, 5 mm spot, 8 Hz, 300 micros pulse, two passes on the upper
      eyelids, four passes on the lower eyelids and six passes on the crow's feet area.
      Soon after the LSR, one side was covered with Flexzan dressing and the other side
      was covered with a new hydrocolloid dressing -- H2460. The side of the dressing
      was randomized by alternating both dressings. All volunteers were evaluated and
      digitally photographed every day for a week and at 1 month after LSR. The degree
      of erythema, swelling, bleeding, oozing, crusting, pigmentary changes, scarring,
      discomfort, itching, burning, ease of application of dressings, initial adhesion,
      overall adhesion, leakage of fluid, maceration of surrounding skin, ease of
      removal and adhesive residue upon removal were documented. RESULTS: In all
      volunteer and investigator's evaluations, the new dressing, H2460, achieved far
      better results than Flexzan in each category. After a 1-week follow-up all
      volunteers and the investigator evaluated the H2460 side as: healed better,
      simple to use, and caused less discomfort in 10 out of 10 volunteers. The blinded
      observer's assessment showed that the Flexzan side healed better in one
      volunteer. CONCLUSION: The new dressing, H2460, is a better and suitable
      alternative to Flexzan as a post LSR dressing.

PMID- 16414911
TI  - Using hand performance measures to predict handedness.
AB  - Handedness is defined by the individual's preference to use one hand
      predominately for unimanual tasks and the ability to perform these tasks more
      efficiently with one hand (Corey, Hurley, & Foundas, 2001). It is important to
      use performance variables to measure handedness because they are more objective
      than traditional hand preference questionnaires (Bryden, Pryde, & Roy, 2000a).
      The current study develops a predictive model of handedness as measured by the
      Waterloo Handedness Questionnaire (WHQ) using several performance indicators of
      handedness. A total of 120 individuals (60 right-handers and 60 left-handers)
      were asked to complete four performance-based tasks: the Grooved Pegboard (GP),
      the Annett pegboard (AP), finger tapping (FT), and grip strength (GS) as well as
      an observational measure of preference, the Wathand Box Test (WBT). Backward
      linear regression analysis showed that the Wathand Box measure and the laterality
      quotients for several performance measures (GP place, AP, and FT) combined to act
      as the most accurate predictors of hand preference. The predictive model of
      handedness developed is as follows: WHQ = -2.760- - 0.667(GP place) + 0.809(FT) +
      0.234(WBT) - 0.748(AP) with an explained variance of 0.836. These results
      illustrate, as Corey et al. (2001) suggested, that the best predictive model of
      handedness combines preference measures and several performance measures that tap
      into different elements of motor performance. By developing this model, it is
      possible to get an accurate measure of handedness using objective measures.

PMID- 16414912
TI  - Arm folding, hand clasping, and Luria's concept of "latent left-handedness".
AB  - Luria (1947/1970) proposed left-top positions in arm folding (AF) and hand
      clasping (HC) to be signs of "latent left-handedness". However, research since
      has revealed that (1) left-top positions are canonical for European right-handers
      and (2) combined AF/HC measures may provide more information about cerebral
      laterality than either measure considered alone. We tested whether AF and HC or
      AF/HC combinations predicted diminished right-handedness for 12 handedness items.
      Results from 509 healthy participants showed that (1) left-top positions in AF
      and HC were dominant across participants, as was right-handedness, and a right
      top position in HC was associated with attenuated right-handedness, (2) right
      hand preference was more frequently associated with congruent AF/HC combinations,
      especially of the LL type (AF: left-top / HC: left-top), and (3) non-right-hand
      preference was associated with non-congruent, predominantly LR combinations. We
      conjecture that the LL type combination indicates left hemispheric dominance for
      motor actions, whereas the LR combination, in which HC as the distally innervated
      posture deviates from the canonical pattern, indicates attenuated hemispheric
      asymmetry. Our data support Luria's proposition that a left-top preference in AF
      points to "latent" left-handedness, but only if associated with a right-top
      preference in HC. Consistent left-top preference for the combined AF/HC measure
      appears to predict right-handedness.

PMID- 16414913
TI  - Discontinuity in the fall of left-handedness in a French population: a May '68
      effect?
AB  - The fall in the prevalence of left-handedness with age has been attributed to the
      effect of forced dextrality on handwriting. The purpose of this study was to
      assess handwriting preference in a cohort of children and adult participants in
      order to study the correlation between age and incidence of sinistrality. A
      strong preference for right handwriting across all ages with a decrease in
      sinistrality with age (18% in those under 20 versus 3% in those over 60) was
      observed. This phenomenon was not continuous, and a dramatic drop at age 30-40
      years might be attributed to changes in educational management during the 1960s,
      especially after the events of May 1968 in France.

PMID- 16414914
TI  - Schizophrenia and rightward bias in line bisection.
AB  - This study investigated line bisection in 10 males with schizophrenia and 15
      controls. There was an overall leftward bias, consistent with slight right
      "pseudoneglect", but the schizophrenia group showed more variation with
      experimental conditions, suggesting impaired interhemispheric transfer.
      Specifically, the rightward bias was especially marked when the lines were
      positioned on the right side of the page, when the right hand was used, and when
      a right to left scan was adopted. The rightward bias was associated with the
      predominance of negative symptoms. Findings are discussed with reference to the
      role of the corpus callosum in the transfer of spatial attention.

PMID- 16414915
TI  - Intermanual transfer of timing control between tasks holding different levels of
      motor complexity.
AB  - Interlateral transfer of learning was investigated in timing tasks holding
      different levels of motor complexity. The tasks required hitting a hemiball at
      the end of an electronic trackway simultaneously with the end of displacement of
      a visual stimulus. The hemiball was to be hit with the palm of one hand (simple
      task), or through a forehand drive with a racquet (complex task). Four
      experimental conditions were compared, which resulted from the combination
      between direction of transfer for complexity, and direction of transfer for hand.
      The results evidenced partial interlateral transfer of timing control, and that
      performance on the transfer task was temporally biased by the practised task.
      Additionally, there was not a consistent advantage for a single direction of
      transfer of learning, which means symmetric capacity of intermanual transfer.
      Such findings indicate that in synchronisation tasks motor learning takes place
      at two levels: at a higher level independent of the effector system, and at a
      lower effector-specific level.

PMID- 16414916
TI  - Do left-handed children have advantages regarding school performance and
      leadership skills?
AB  - A handedness polymorphism exists in all human populations so far investigated, at
      least since the Palaeolithic. Handedness is a heritable trait, and a possible
      evolutionary explanation for the higher prevalence of right-handers is the
      association of left-handedness with some deleterious traits. In this context, the
      persistence of left-handers remains unexplained. Reproductive success has been
      shown to be dependent on cultural success in many human societies. This study is
      the first attempt to consider the importance of social status to evolutionary
      processes related to handedness. We conducted a survey in French public primary
      schools to look for a possible association between laterality, school
      performance, and leadership skills. This study revealed only weak associations,
      and a sex effect. For primary-school girls, we report a negative association
      between several indicators of left-sidedness and teacher's ratings of school
      performance and leadership skills. For primary-school boys, we report a positive
      association between left-handedness for writing and teacher's ratings of school
      performance. The present study did not reveal any strong relation between
      laterality and school performance, but has shown that general school performance
      is not independent of laterality, and that the effect is opposite in males and
      females. The main difficulty is now to define clearly the different intellectual
      functions involved.

PMID- 16414917
TI  - Drawing on either side of the brain.
AB  - Although both the cerebral laterality of processing visual information and human
      drawing skill have long been sources of investigation, there is not much
      empirical work combining the two. In this study, an attempt was made to explore
      if known different specialisations of the two cerebral hemispheres could help in
      predicting qualities of drawings produced by each hand. For this purpose, an
      amateur artist who is able to draw with either the left or the right hand
      produced a series of realistic drawings of 3D objects. Then 28 participants rated
      the drawings for several predetermined perceptual and aesthetic properties. The
      participants judged drawings made with the left hand as superior to those made
      with the right hand. Given that the right hemisphere controls the left hand, we
      suggest that this hand might also benefit from the more direct access to
      lateralised areas that are involved in the processing aspects of visual
      information and spatial properties (e.g., depth and shading). These perceptual
      processes may thus play an important role in the ability to draw realistic
      depictions of objects.

PMID- 16414918
TI  - Does the presence of psychological distress in patients influence their choice of
      sitting position in face-to-face consultation with the GP?
AB  - Evidence exists that when a person is required to position him/herself to the
      right or left of another during a face-to-face encounter, the orientation chosen
      is influenced by the biases of visual attention. It is also known that such
      attentive biases may be disturbed in states of anxiety and depression. The aim of
      the present study was to investigate whether an association could be found
      between the presence of psychological distress in patients and their choice of
      lateral orientation relative to the doctor during face-to-face consultations.
      Patients routinely attending their GP (the author) were obliged to choose to sit
      either to the right or left for the face-on encounter. They then completed the
      Hospital Anxiety and Depression Scale questionnaire (HADS), its two subscales (0
      21) measuring symptoms of anxiety and depression reported by patients. "Cases" of
      anxiety and/or depression were identified as those patients who scored > 8 on
      either or both subscales. Of the 756 patients studied, case status was
      significantly associated with seating preference (p = .001): 234 (58%) cases
      sitting on the left versus 107 (30%) non-cases. Handedness was not directly
      associated with seating preference, but did modify the case status-seating
      preference association. Thus among right-handers 213 (59%) cases sat on the left
      versus 85 (27%) non-cases, giving an odds ratio (sitting on the left) for cases
      versus non-cases of 4.0. For left-handers the odds ratio (sitting left) for cases
      versus non-cases was 0.54, although the small number of left-handers precluded
      statistical significance being achieved in this group. These results support the
      notion that orienting behaviour is influenced by biases of visual attention
      linked to handedness and that attentive biases may be disturbed in states of
      anxiety and depression.

PMID- 16414920
TI  - Interspecific variation in nighttime transpiration and stomatal conductance in a
      mixed New England deciduous forest.
AB  - Transpiration is generally assumed to be insignificant at night when stomata
      close in response to the lack of photosynthetically active radiation. However,
      there is increasing evidence that the stomata of some species remain open at
      night, which would allow for nighttime transpiration if there were a sufficient
      environmental driving force. We examined nighttime water use in co-occurring
      species in a mixed deciduous stand at Harvard Forest, MA, using whole-tree and
      leaf-level measurements. Diurnal whole-tree water use was monitored continuously
      with Granier-style sap flux sensors in paper birch (Betula papyrifera Marsh.),
      red oak (Quercus rubra L.) and red maple (Acer rubrum L.). An analysis was
      conducted in which nighttime water flux could be partitioned between refilling of
      internal water stores and transpiration. Substantial nighttime sap flux was
      observed in all species and much of this flux was attributed to the refilling of
      depleted water stores. However, in paper birch, nighttime sap flux frequently
      exceeded recharge estimates. Over 10% of the total daily sap flux during the
      growing season was due to transpiration at night in paper birch. Nighttime sap
      flux was over 8% of the total daily flux in red oak and 2% in red maple; however,
      this flux was mainly associated with recharge. On nights with elevated vapor
      pressure deficit, sap flux continued through the night in paper birch, whereas it
      reached zero during the night in red oak and red maple. Measurements of leaf
      level gas exchange on a night with elevated vapor pressure deficit showed
      stomatal conductance dropping by only 25% in paper birch, while approaching zero
      in red oak and red maple. The study highlighted differences in ecophysiological
      controls on sap flux exerted by co-occurring species. Paper birch is a fast
      growing, shade-intolerant species with an earlier successional status than red
      oak and red maple. Risking water loss through nighttime transpiration may provide
      paper birch with an ecological advantage by enabling the species to maximize
      photosynthesis and support rapid growth. Nighttime transpiration may also be a
      mechanism for delivering oxygen to respiring cells in the deep sapwood of paper
      birch.

PMID- 16414919
TI  - Transgenic sterility in Populus: expression properties of the poplar PTLF,
      Agrobacterium NOS and two minimal 35S promoters in vegetative tissues.
AB  - Transgenic sterility is a desirable trait for containment of many kinds of
      transgenes and exotic species. Genetically engineered floral sterility can be
      imparted by expression of a cytotoxin under the control of a predominantly floral
      tissue-specific promoter. However, many otherwise desirable floral promoters
      impart substantial non-floral expression, which can impair plant health or make
      it impossible to regenerate transgenic plants. We are therefore developing a
      floral sterility system that is capable of attenuating undesired background
      vegetative expression. As a first step towards this goal, we compared the
      vegetative expression properties of the promoter of the poplar (Populus
      trichocarpa Torr. & Gray) homolog of the floral homeotic gene LEAFY (PTLF), which
      could be used to impart male and female flower sterility, to that of three
      candidate attenuator-gene promoters: the cauliflower mosaic virus (CaMV) 35S
      basal promoter, the CaMV 35S basal promoter fused to the TMV omega element and
      the nopaline synthase (NOS) promoter. The promoters were evaluated via
      promoter::GUS gene fusions in a transgenic poplar hybrid (Populus tremula L. x P.
      alba L.) by both histochemical and fluorometric GUS assays. In leaves, the NOS
      promoter conveyed the highest activity and had a mean expression level 5-fold
      higher than PTLF, whereas the CaMV 35S basal promoter fused to the omega element
      and the CaMV 35S basal promoter alone directed mean expression levels that were
      0.5x and 0.35x that of PTLF, respectively. Differential expression in shoots,
      leaves, stems and roots was observed only for the NOS and PTLF promoters.
      Strongest expression was observed in roots for the NOS promoter, whereas the PTLF
      promoter directed highest expression in shoots. The NOS promoter appears best
      suited to counteract vegetative expression of a cytotoxin driven by the PTLF
      promoter where 1:1 toxin:attenuator expression is required.

PMID- 16414921
TI  - Temperature regulation of bud-burst phenology within and among years in a young
      Douglas-fir (Pseudotsuga menziesii) plantation in western Washington, USA.
AB  - Past research has established that terminal buds of Douglas-fir (Pseudotsuga
      menziesii (Mirb.) Franco) seedlings from many seed sources have a chilling
      requirement of about 1200 h at 0-5 degrees C; once chilled, temperatures > 5
      degrees C force bud burst via accumulation of heat units. We tested this
      sequential bud-burst model in the field to determine whether terminal buds of
      trees in cooler microsites, which receive less heat forcing, develop more slowly
      than those in warmer microsites. For three years we monitored terminal bud
      development in young saplings as well as soil and air temperatures on large,
      replicated plots in a harvest unit; plots differed in microclimate based on
      amount of harvest residue and shade from neighboring stands. In two of three
      years, trees on cooler microsites broke bud 2 to 4 days earlier than those on
      warmer microsites, despite receiving less heat forcing from March to May each
      year. A simple sequential model did not predict cooler sites having earlier bud
      burst nor did it correctly predict the order of bud burst across the three years.
      We modified the basic heat-forcing model to initialize, or reset to zero, the
      accumulation of heat units whenever significant freezing temperature events (> or
      = 3 degree-hours day(-1) < 0 degrees C) occurred; this modified model correctly
      predicted the sequence of bud burst across years. Soil temperature alone or in
      combination with air temperature did not improve our predictions of bud burst.
      Past models of bud burst have relied heavily on data from controlled experiments
      with simple temperature patterns; analysis of more variable temperature patterns
      from our 3-year field trial, however, indicated that simple models of bud burst
      are inaccurate. More complex models that incorporate chilling hours, heat
      forcing, photoperiod and the occurrence of freeze events in the spring may be
      needed to predict effects of future silvicultural treatments as well to interpret
      the implications of climate-change scenarios. Developing and testing new models
      will require data from both field and controlled-environment experiments.

PMID- 16414922
TI  - Callose in root apices of European chestnut seedlings: a physiological indicator
      of aluminum stress.
AB  - We determined if callose formation in 1-cm-long root apices of European chestnut
      (Castanea sativa Mill.) seedlings is affected by naturally occurring high
      concentrations of aluminum (Al) under laboratory conditions and by low base
      saturation (BS) of soils under forest field conditions. Under controlled
      conditions in the laboratory, seedlings were treated with simulated soil
      solutions in the presence or absence (control) of Al. One day after exposing
      seedlings to a simulated soil solution containing 168 microM Al, callose
      formation in the root apices had increased significantly. After 7 days, callose
      concentration in root apices was significantly correlated with the concentration
      of free Al3+ ions recovered in the simulated soil solution and with the
      concentration of Al in fine roots. At four field sites in southern Switzerland,
      seedlings were grown for five months in either A-horizon soil with a BS above 17%
      or in a B-horizon soil with a BS below 5%. Callose concentrations were
      significantly higher in root apices in the B horizon than in the A horizon.
      Callose concentrations in root apices were negatively correlated with Ca/Al molar
      ratio in fine roots. We conclude that callose in the root apices of European
      chestnut could be a useful physiological parameter for assessing Al toxicity
      under both laboratory and field conditions.

PMID- 16414923
TI  - Tradeoff between shade adaptation and mitigation of photoinhibition in leaves of
      Quercus mongolica and Acer mono acclimated to deep shade.
AB  - We investigated susceptibility to photoinhibition in leaves acclimated to
      different light regimes in intermediately shade-tolerant Japanese oak (Quercus
      mongolica Fisch. ex Turcz. var. crispula (Blume) Ohashi) and shade-tolerant
      Japanese maple (Acer mono Maxim. var. glabrum (Lev. et Van't.) Hara), to
      elucidate adaptability to gap formation in leaves differing in shade acclimation.
      We hypothesized that there is a tradeoff between shade adaptation and capacity to
      mitigate photoinhibition associated with leaf morphology. We simultaneously
      measured chlorophyll fluorescence and gas exchange in seedlings that had been
      grown in full sunlight (open), 10% of full sun (moderate shade) and 5% of full
      sun (deep shade). Shade-tolerant A. mono adapted to deep shade through changes in
      leaf morphology, lowering its leaf mass per area (LMA), but Q. mongolica showed
      little change in LMA between moderate and deep shade. Photochemical quenching
      (qP) did not differ between species in full sunlight and moderate shade; however,
      in deep shade, qP of Q. mongolica was higher than that of A. mono, suggesting
      that Q. mongolica grown in deep shade is less susceptible to photoinhibition at
      gap formation. This is consistent with the finding that chronic photoinhibition 3
      days after the transfer to full sunlight, indicated by the decrease in maximum
      photochemical efficiency, Fv/Fm, at predawn, was less in deep-shade-grown Q.
      mongolica than in deep shade-grown A. mono. In deep shade, the electron transport
      rate (ETR) of Q. mongolica was higher than that of A. mono, whereas thermal
      energy dissipation through photosystem II antennae, indicated by non
      photochemical quenching, was lower in Q. mongolica than in A. mono. In deep
      shade, the greater ETR capacity in Q. mongolica in association with higher LMA
      and higher leaf N content could contribute to maintaining high qP and mitigating
      photoinhibition. These results indicate that, by maintaining a high electron
      transport capacity even in deep shade, the gap-dependent and intermediate-shade
      tolerant Q. mongolica trades improved shade adaptation for higher growth
      potential when a gap event occurs.

PMID- 16414925
TI  - Carbon content variation in boles of mature sugar maple and giant sequoia.
AB  - At present, a carbon (C) content of 50% (w/w) in dry wood is widely accepted as a
      generic value; however, few wood C measurements have been reported. We used
      elemental analysis to investigate C content per unit of dry matter and observed
      that it varied both radially and vertically in boles of two old-growth tree
      species: sugar maple (Acer saccharum Marsh.) and giant sequoia (Sequoiadendron
      giganteum (Lindl.) Bucholz). In sugar maple there was considerable variation in
      tree ring widths among four radii for particular annual layers of xylem,
      revealing that the annual rate of C assimilation differs around the circumference
      and from the base of each tree to its top, but the observed variation in C
      content was unrelated to diameter growth rate and strongly related to the
      calendar year when the wood was formed. Carbon content in sugar maple wood
      increased in an approximately linear fashion, from < 50 to 51% from pith to
      cambium, at both the base and top of the boles. In giant sequoia, C was
      essentially constant at > 55% across many hundreds of years of heartwood, but it
      declined abruptly at the sapwood-heartwood boundary and remained lower in all
      sapwood samples, an indication that heartwood formation involves anabolic
      metabolism. Factors that may be responsible for the different C contents and
      trends with age between sugar maple and sequoia trees are considered. Tree-ring
      data from this study do not support some of the key assumptions made by
      dendrochronology.

PMID- 16414924
TI  - Leaf turnover and growth responses of shade-grown saplings of four Shorea rain
      forest species to a sudden increase in light.
AB  - We tested the hypothesis that sapling growth following a sudden increase in solar
      irradiance is related to recovery from photoinhibition and the balance between
      rate of production of new leaves and rate of abscision of old leaves. Leaf gas
      exchange, chlorophyll fluorescence and relative growth rate (RGR) of stem basal
      area were measured following the sudden exposure of shade-grown (7% of full
      sunlight) saplings of four Shorea species to full sunlight. Sudden exposure to
      full sunlight resulted in an immediate and substantial reduction in dark-adapted
      quantum yield of photosystem II (Fv/Fm), followed by a gradual recovery in all
      species. Near light-saturated net assimilation rate (A max) and area-based leaf
      chlorophyll concentration ([Chl area]) also declined immediately after exposure.
      Eleven days after exposure, A max had recovered to pre-exposure values in all
      species, whereas [Chl area] had not recovered. Across species, RGR of stem basal
      area increased with increasing RGR of the number of leaves following exposure to
      full sunlight. The interspecific variations in RGR of stem basal area suggest
      that new leaf production is crucial for determining the potential growth of
      saplings following gap formation.

PMID- 16414926
TI  - Mitigation of effects of extreme drought during stage III of peach fruit
      development by summer pruning and fruit thinning.
AB  - A water deficit during stage III of fruit growth was established with the aim of
      determining if it is possible to achieve an improvement in tree water status by
      summer pruning and fruit thinning. The experiment was set up as a randomized
      block split-plot design across trials (irrigation) where pruning was assigned to
      the main plot and fruit thinning to the sub-plots. The irrigation treatments were
      (1) standard full irrigation (FI), and (2) suppression of irrigation during stage
      III of fruit growth until leaves visibly withered (LWI); the pruning treatments
      were (1) experimental summer pruning (EP), and (2) standard summer pruning (CP);
      and three fruit thinning intensities were applied to facilitate analysis of the
      effects of the treatments in relation to fruit load. Changes in amount of light
      intercepted and in tree stem water potential (Psi stem) were evaluated. The EP
      treatment reduced the amount of light intercepted by the tree. In the FI
      treatment, there was a significant reduction in fruit growth measured as both
      water accumulation and dry mass accumulation. Under FI conditions, reductions in
      fruit load as a result of EP were not accompanied by a significant improvement in
      Psi stem. In the LWI treatment, EP produced a significant improvement of 0.17 MPa
      in Psi stem, but there was no improvement in fruit growth compared with CP trees.
      A reduction in fruit load from 350 (commercial load) to 150 per tree
      significantly improved Psi stem by 0.3 MPa at the end of stage III of fruit
      growth. These results indicate that improvements in water status in response to
      pruning may be insufficient to promote fruit growth if the pruned trees are
      unable to provide an adequate supply of assimilates to the developing fruits.

PMID- 16414927
TI  - Leaf and wood carbon isotope ratios, specific leaf areas and wood growth of
      Eucalyptus species across a rainfall gradient in Australia.
AB  - Leaves and samples of recent wood of Eucalyptus species were collected along a
      rainfall gradient parallel to the coast of Western Australia between Perth in the
      north and Walpole in the south and along a southwest to northeast transect from
      Walpole in southwestern Australia, to near Mount Olga in central Australia. The
      collection included 65 species of Eucalyptus sampled at 73 sites and many of the
      species were collected at several sites along the rainfall gradient. Specific
      leaf area (SLA) and isotopic ratio of 13C to 12C (delta 13C) of leaves that grew
      in 2002, and tree ring growth and delta 13C of individual cell layers of the wood
      were measured. Rainfall data were obtained from the Australian Bureau of
      Meteorology for 29 locations that represented one or a few closely located
      collection sites. Site-averaged data and species-specific values of delta 13C
      decreased with decreasing annual rainfall between 1200 and 300 mm at a rate of
      1.63 per thousand per 1000 mm decrease in rainfall. Responses became variable in
      the low rainfall region (< 300 mm), with some species showing decreasing delta
      13C with rainfall, whereas delta 13C increased or remained constant in other
      species. The range of delta 13C values in the low rainfall region was as large as
      the range observed at sites receiving > 300 mm of annual rainfall. Specific leaf
      area varied between 2 and 6 m2 kg(-1) and tended to increase with decreasing
      annual rainfall in some species, but not all, whereas delta 13C decreased with
      SLA. The relationship between delta 13C and SLA was highly species and soil-type
      specific. Leaf-area-based nitrogen (N) content varied between 2 and almost 6 g m(
      2) and decreased with rainfall. Thus, thicker leaves were associated with higher
      N content and this compensated for the effect of drought on delta 13C. Nitrogen
      content was also related to soil type and species identity. Based on a linear
      mixed model, statistical analysis of the whole data set showed that 27% of the
      variation in delta 13C was associated with changes in SLA, 16% with soil type and
      only 1% with rainfall. Additionally, 21% was associated with species identity.
      For a subset of sites with > 300 mm rainfall, 43% of the variation was explained
      by SLA, 13% by soil type and only 3% by rainfall. The species effect decreased to
      9% because there were fewer species in the subset of sites. The small effect of
      rainfall on delta 13C was further supported by a path analysis that yielded a
      standardized path coefficient of 0.38 for the effect of rainfall on SLA and -0.50
      for the effect of SLA on delta 13C, but an insignificantly low standardized path
      coefficient of -0.05 for the direct effect of rainfall on delta 13C. Thus, in
      contrast to our hypothesis that delta 13C decreases with rainfall independent of
      soil type and species, we detected no statistically significant relationship
      between rainfall and delta 13C in leaves of trees growing at sites receiving <
      300 mm of rainfall annually. Rainfall affected delta 13C indirectly through soil
      type (a surrogate for water-holding capacity) across the rainfall gradient.
      Annual tree rings are not clearly visible in evergreen Eucalyptus species, even
      in the seasonally cool climate of SW Australia. Generally, visible density
      transitions in the wood are related not to a strict annual cycle but to periods
      of growth associated mainly with rainfall. The relationship between delta 13C of
      leaves and the width of these stem increments was not statistically significant.
      Analysis of stem growth periods showed that delta 13C in wood responded to
      rainfall events, but carbohydrate storage and reallocation also affected the
      isotopic signature. Although delta 13C in wood of any one species varied over a
      range of 2 to 4 per thousand, there was a general relationship between delta 13C
      of the leaves and the annual range of delta 13C in wood. We conclude that species
      specific traits are important in understanding the response of Eucalyptus to
      rainfall and that the diversity of the genus may reflect its response to the
      large climatic gradient in Australia and to the large annual and interannual
      variations in rainfall at any one location.

PMID- 16414928
TI  - Restoration thinning and influence of tree size and leaf area to sapwood area
      ratio on water relations of Pinus ponderosa.
AB  - Ponderosa pine (Pinus ponderosa Dougl. ex P. Laws) forest stand density has
      increased significantly over the last century (Covington et al. 1997). To
      understand the effect of increased intraspecific competition, tree size (height
      and diameter at breast height (DBH)) and leaf area to sapwood area ratio
      (A(L):A(S)) on water relations, we compared hydraulic conductance from soil to
      leaf (kl) and transpiration per unit leaf area (Q(L)) of ponderosa pine trees in
      an unthinned plot to trees in a thinned plot in the first and second years after
      thinning in a dense Arizona forest. We calculated kl and Q(L) based on whole-
      tree sap flux measured with heat dissipation sensors. Thinning increased tree
      predawn water potential within two weeks of treatment. Effects of thinning on kl
      and Q(L) depended on DBH, A(L):A(S) and drought severity. During severe drought
      in the first growing season after thinning, kl and Q(L) of trees with low
      A(L):A(S) (160-250 mm DBH; 9-11 m height) were lower in the thinned plot than the
      unthinned plot, suggesting a reduction in stomatal conductance (g(s)) or reduced
      sapwood specific conductivity (K(S)), or both, in response to thinning. In
      contrast kl and Q(L) were similar in the thinned plot and unthinned plot for
      trees with high A(L):A(S) (260-360 mm DBH; 13-16 m height). During non-drought
      periods, kl and Q(L) were greater in the thinned plot than in the unthinned plot
      for all but the largest trees. Contrary to previous studies of ponderosa pine,
      A(L):A(S) was positively correlated with tree height and DBH. Furthermore, kl and
      Q(L) showed a weak negative correlation with tree height and a strong negative
      correlation with A(S) and thus A(L):A(S) in both the thinned and unthinned plots,
      suggesting that trees with high A(L):A(S) had lower g(s). Our results highlight
      the important influence of stand competitive environment on tree-size-related
      variation in A(L):A(S) and the roles of A(L):A(S) and drought on whole-tree water
      relations in response to thinning.

PMID- 16414929
TI  - Vigor-controlling rootstocks affect early shoot growth and leaf area development
      of kiwifruit.
AB  - Patterns of shoot development and the production of different types of shoots
      were compared with scion leaf area index (LAI) to identify how eight clonal
      Actinidia rootstocks influence scion development. Rootstocks selected from seven
      Actinidia species (A. chrysantha Merri., A. deliciosa (A. Chev.) C. F. Liang et
      A.R. Ferguson, A. eriantha Benth., A. hemsleyana Dunn, A. kolomikta (Maxim. et
      Rupr.) Maxim., A. kolomikta C.F. Liang and A. polygama (Sieb. et Zucc.) Maxim.)
      were grafted with the scion Actinidia chinensis Planch. var. chinensis 'Hort16A'
      (yellow kiwifruit). Based on an earlier architectural analysis of A. chinensis,
      axillary shoot types produced by the scion were classified as short, medium or
      long. Short and medium shoots produced a restricted number of preformed leaves
      before the shoot apex ceased growth and aborted, resulting in a 'terminated'
      shoot. The apex of long shoots continued growth and produced more nodes
      throughout the growing seasons. Mid-season LAI of the scion was related to the
      proportion of shoots that ceased growth early in the season. Scions on low-vigor
      rootstocks had 50% or less leaf area than scions on the most vigorous rootstocks
      and had a higher proportion of short and medium shoots. On low-vigor rootstocks,
      a higher proportion of short shoots was retained during pruning to form the
      parent structure of the following year. Short parent shoots produced a higher
      proportion of short daughter shoots than long parent shoots, thus reinforcing the
      effect of the low-vigor rootstocks. However, overall effects of rootstock on
      shoot development were consistent regardless of parent shoot type and nodal
      position within the parent shoot. Slower-growing shoots were more likely to
      terminate and scions on low-vigor rootstocks produced a higher proportion of slow
      growing shoots. Shoot termination also occurred earlier on low-vigor rootstocks.
      The slower growth of terminating shoots was detectable from about 20 days after
      bud burst. Removal of a proportion of shoots at the end of bud burst increased
      the growth rate and decreased the frequency of termination of the remaining
      shoots on all rootstocks, indicating that the fate of a shoot was linked to
      competitive interactions among shoots during initial growth immediately after bud
      burst. Rootstock influenced the process of shoot termination independently of its
      effect on final leaf size. Scions on low-vigor rootstocks had a higher proportion
      of short shoots and short shoots on all rootstocks had smaller final leaf sizes
      at equivalent nodes than medium or long shoots. Only later in the development of
      long shoots was final leaf size directly related to rootstock, with smaller
      leaves on low-vigor rootstocks. Thus, the most important effect of these
      Actinidia rootstocks on scion development occurred during the initial period of
      shoot growth immediately after bud burst.

PMID- 16414930
TI  - Soluble sugars mediate sink feedback down-regulation of leaf photosynthesis in
      field-grown Coffea arabica.
AB  - Source-sink relationships of field-grown plants of Coffea arabica L. cultivar
      'Caturra' were manipulated to analyze the contribution of soluble sugars to sink
      feedback down-regulation of maximal leaf net CO2 assimilation rate (Amax). Total
      soluble sugar concentration (SSCm) and Amax were measured in the morning and
      afternoon on mature leaves of girdled branches bearing either high or low fruit
      loads. Leaf Amax was negatively correlated to SSCm, increased with fruit load and
      decreased during the day, indicating that limiting sink demand for carbohydrates
      caused SSCm to accumulate in the leaf tissue which results in down-regulation of
      Amax. To further analyze source-sink feedback on Amax, we compared Amax of
      mature, non-sink-limited coffee leaves fed with water or sucrose for 5, 10 or 30
      min with that of non-fed control leaves. Sucrose-feeding reduced Amax compared
      with the control and water-feeding treatments, indicating that down-regulation of
      Amax is related to phloem sucrose concentration in coffee source leaves,
      independent of SSCm concentration in other leaf tissues. Although sucrose
      appeared to be more closely related to the mechanism underlying sink feedback
      down-regulation of Amax in coffee leaves than SSCm, Amax was closely related to
      SSCm by a nonlinear equation that may be useful for integrating sink limitations
      in coffee leaf photosynthetic models.

PMID- 16414931
TI  - Translocation of nitrogen in the xylem of field-grown cherry and poplar trees
      during remobilization.
AB  - Studies of small trees growing in pots have established that individual amino
      acids or amides are translocated in the xylem sap of a range of tree species
      following bud burst, as a consequence of nitrogen (N) remobilization from
      storage. This paper reports the first study of N translocation in the xylem of
      large, deciduous, field-grown trees during N remobilization in the spring. We
      applied 15N fertilizer to the soil around 10-year-old Prunus avium L. and Populus
      trichocharpa Torr. & Gray ex Hook var. Hastata (Dode) A. Henry x Populus
      balsamifera L. var. Michauxii (Dode) Farwell trees before bud burst to label N
      taken up by the roots. Recovery of unlabeled N in xylem sap and leaves was used
      to demonstrate that P. avium remobilizes N in both glutamine (Gln) and asparagine
      (Asn). Sap concentrations of both amides rose sharply after bud burst, peaking 14
      days after bud burst for Gln, and remaining high some 45 days for Asn. There was
      no 15N enrichment of either amide until 21 days after bud burst. In the Populus
      trees, nearly all the N was translocated in the sap as Gln, the concentration of
      which peaked and then declined before the amide was enriched with 15N, 40 days
      after bud burst. Xylem sap of clonal P. avium trees was sampled at different
      positions in the crown to assess if the amino acid and amide composition of the
      sap varied within the crown. Sap was sampled during remobilization (when the
      concentration of Gln was maximal), at the end of remobilization and at the end of
      the experiment (68 days after bud burst). Although the date of sampling had a
      highly significant effect on sap composition, the effect of position of sampling
      was marginal. The results are discussed in relation to N translocation in adult
      trees and the possibility of measuring N remobilization by calculating the flux
      of N translocation in the xylem.

PMID- 16414932
TI  - Preformation in vegetative buds of Prunus persica: factors influencing number of
      leaf primordia in overwintering buds.
AB  - We investigated the influence of bud position, cultivar, tree age, tree
      carbohydrate status, sampling date, drought and light exposure on the number of
      leaf primordia formed in dormant vegetative peach buds (Prunus persica (L.)
      Batsch) relative to the number of primordia formed after bud break (neoformed).
      During winter dormancy, vegetative peach buds from California and Italy were
      dissected and the number of leaf primordia recorded. Between leaf drop and bud
      break, the number of leaf primordia doubled from about five to about 10. Parent
      shoot length, number of nodes on the parent shoot, cross-sectional area of the
      parent shoot, bud position along the parent shoot and bud cross-sectional area
      were correlated with the number of leaf primordia. Previous season light
      exposure, drought and tree carbohydrate status did not affect the number of leaf
      primordia present. The number of leaf primordia differed significantly among
      peach varieties and tree ages at leaf drop, but not at bud break. Our results
      indicate that neoformation accounted for all shoot growth beyond about 10 nodes.
      The predominance of neoformed shoot growth in peach allows this species great
      plasticity in its response to current-season conditions.

PMID- 16414933
TI  - The cover. Madonna and Child.

PMID- 16414934
TI  - Role of environment in addiction probed.

PMID- 16414935
TI  - Carotid artery surgery guidelines updated: new data also support stents in high
      risk cases.

PMID- 16414936
TI  - Cancer survivors need better care: new report makes recommendations.

PMID- 16414937
TI  - Novel lupus therapies show promise.

PMID- 16414938
TI  - Schizophrenia and the Chinese famine of 1959-1961.

PMID- 16414939
TI  - Mortality following prostate cancer recurrence after radical prostectomy.

PMID- 16414940
TI  - Hypertension in adults across age groups.

PMID- 16414941
TI  - Hypertension in adults across age groups.

PMID- 16414942
TI  - Endocarditis from Staphylococcus aureus.

PMID- 16414943
TI  - Endocarditis from Staphylococcus aureus.

PMID- 16414944
TI  - Genetic testing in the long QT syndrome: development and validation of an
      efficient approach to genotyping in clinical practice.
AB  - CONTEXT: In long QT syndrome (LQTS), disease severity and response to therapy
      vary according to the genetic loci. There exists a critical need to devise
      strategies to expedite genetic analysis. OBJECTIVE: To perform genetic screening
      in patients with LQTS to determine the yield of genetic testing, as well as the
      type and the prevalence of mutations. DESIGN, PATIENTS, AND SETTING: We
      investigated whether the detection of a set of frequently mutated codons in the
      KCNQ1, KCNH2, and SCN5A genes may translate in a novel strategy for rapid
      efficient genetic testing of 430 consecutive patients referred to our center
      between June 1996 and June 2004. The entire coding regions of KCNQ1, KCNH2,
      SCN5A, KCNE1, and KCNE2 were screened by denaturing high-performance liquid
      chromatography and DNA sequencing. The frequency and the type of mutations were
      defined to identify a set of recurring mutations. A separate cohort of 75
      consecutive probands was used as a validation group to quantify prospectively the
      prevalence of the recurring mutations identified in the primary LQTS population.
      MAIN OUTCOME MEASURES: Development of a novel approach to LQTS genotyping.
      RESULTS: We identified 235 different mutations, 138 of which were novel, in 310
      (72%) of 430 probands (49% KCNQ1, 39% KCNH2, 10% SCN5A, 1.7% KCNE1, and 0.7%
      KCNE2). Fifty-eight percent of probands carried nonprivate mutations in 64 codons
      of KCNQ1, KCNH2, and SCN5A genes. A similar occurrence of mutations at these
      codons (52%) was confirmed in the prospective cohort of 75 probands and in
      previously published LQTS cohorts. CONCLUSIONS: We have developed an approach to
      improve the efficiency of genetic screening for LQTS. This novel method may
      facilitate wider access to genotyping resulting in better risk stratification and
      treatment of LQTS patients.

PMID- 16414945
TI  - Prevalence and cardiovascular disease correlates of low cardiorespiratory fitness
      in adolescents and adults.
AB  - CONTEXT: Population surveys indicate that physical activity levels are low in the
      United States. One consequence of inactivity, low cardiorespiratory fitness, is
      an established risk factor for cardiovascular disease (CVD) morbidity and
      mortality, but the prevalence of cardiorespiratory fitness has not been
      quantified in representative US population samples. OBJECTIVES: To describe the
      prevalence of low fitness in the US population aged 12 through 49 years and to
      relate low fitness to CVD risk factors in this population. DESIGN, SETTING, AND
      PARTICIPANTS: Inception cohort study using data from the cross-sectional
      nationally representative National Health and Nutrition Examination Survey 1999
      2002. Participants were adolescents (aged 12-19 years; n = 3110) and adults (aged
      20-49 years; n = 2205) free from previously diagnosed CVD who underwent
      submaximal graded exercise treadmill testing to achieve at least 75% to 90% of
      their age-predicted maximum heart rate. Maximal oxygen consumption (VO2max) was
      estimated by measuring the heart rate response to reference levels of submaximal
      work. MAIN OUTCOME MEASURES: Low fitness defined using percentile cut points of
      estimated VO2max from existing external referent populations; anthropometric and
      other CVD risk factors measured according to standard methods. RESULTS: Low
      fitness was identified in 33.6% of adolescents (approximately 7.5 million US
      adolescents) and 13.9% of adults (approximately 8.5 million US adults); the
      prevalence was similar in adolescent females (34.4%) and males (32.9%) (P = .40)
      but was higher in adult females (16.2%) than in males (11.8%) (P = .03). Non
      Hispanic blacks and Mexican Americans were less fit than non-Hispanic whites. In
      all age-sex groups, body mass index and waist circumference were inversely
      associated with fitness; age- and race-adjusted odds ratios of overweight or
      obesity (body mass index > or =25) ranged from 2.1 to 3.7 (P<.01 for all),
      comparing persons with low fitness with those with moderate or high fitness.
      Total cholesterol levels and systolic blood pressure were higher and levels of
      high-density lipoprotein cholesterol were lower among participants with low vs
      high fitness. CONCLUSION: Low fitness in adolescents and adults is common in the
      US population and is associated with an increased prevalence of CVD risk factors.

PMID- 16414946
TI  - Use of gastric acid-suppressive agents and the risk of community-acquired
      Clostridium difficile-associated disease.
AB  - CONTEXT: Recent reports suggest an increasing occurrence and severity of
      Clostridium difficile-associated disease. We assessed whether the use of gastric
      acid-suppressive agents is associated with an increased risk in the community.
      OBJECTIVE: To determine whether the use of gastric acid-suppressive agents
      increases the risk of C difficile-associated disease in a community population.
      DESIGN, SETTING, AND PATIENTS: We conducted 2 population-based case-control
      studies using the United Kingdom General Practice Research Database (GPRD). In
      the first study, we identified all 1672 cases of C difficile recorded between
      1994 and 2004 among all patients registered for at least 2 years in each
      practice. Each case was matched to 10 controls on calendar time and the general
      practice. In the second study, a subset of these cases defined as community
      acquired, that is, not hospitalized in the prior year, were matched on practice
      and age with controls also not hospitalized in the prior year. MAIN OUTCOME
      MEASURES: The incidence of C difficile and risk associated with gastric acid
      suppressive agent use. RESULTS: The incidence of C difficile in patients
      diagnosed by their general practitioners in the General Practice Research
      Database increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in
      2004. The adjusted rate ratio of C difficile-associated disease with current use
      of proton pump inhibitors was 2.9 (95% confidence interval [CI], 2.4-3.4) and
      with H2-receptor antagonists the rate ratio was 2.0 (95% CI, 1.6-2.7). An
      elevated rate was also found with the use of nonsteroidal anti-inflammatory drugs
      (rate ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSIONS: The use of acid-suppressive
      therapy, particularly proton pump inhibitors, is associated with an increased
      risk of community-acquired C difficile. The unexpected increase in risk with
      nonsteroidal anti-inflammatory drug use should be investigated further.

PMID- 16414947
TI  - Erectile dysfunction and subsequent cardiovascular disease.
AB  - CONTEXT: The risk factors for cardiovascular disease and erectile dysfunction are
      similar. OBJECTIVE: To examine the association of erectile dysfunction and
      subsequent cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Men aged 55
      years or older who were randomized to the placebo group (n = 9457) in the
      Prostate Cancer Prevention Trial at 221 US centers were evaluated every 3 months
      for cardiovascular disease and erectile dysfunction between 1994 and 2003.
      Proportional hazards regression models were used to evaluate the association of
      erectile dysfunction and cardiovascular disease. In an adjusted model, covariates
      included age, body mass index, blood pressure, serum lipids, diabetes, family
      history of myocardial infarction, race, smoking history, physical activity, and
      quality of life. MAIN OUTCOME MEASURES: Erectile dysfunction and cardiovascular
      disease. RESULTS: Of the 9457 men randomized to placebo, 8063 (85%) had no
      cardiovascular disease at study entry; of these men, 3816 (47%) had erectile
      dysfunction at study entry. Among the 4247 men without erectile dysfunction at
      study entry, 2420 men (57%) reported incident erectile dysfunction after 5 years.
      After adjustment, incident erectile dysfunction was associated with a hazard
      ratio of 1.25 (95% confidence interval [CI], 1.02-1.53; P = .04) for subsequent
      cardiovascular events during study follow-up. For men with either incident or
      prevalent erectile dysfunction, the hazard ratio was 1.45 (95% CI, 1.25-1.69;
      P<.001). For subsequent cardiovascular events, the unadjusted risk of an incident
      cardiovascular event was 0.015 per person-year among men without erectile
      dysfunction at study entry and was 0.024 per person-year for men with erectile
      dysfunction at study entry. This association was in the range of risk associated
      with current smoking or a family history of myocardial infarction. CONCLUSIONS:
      Erectile dysfunction is a harbinger of cardiovascular clinical events in some
      men. Erectile dysfunction should prompt investigation and intervention for
      cardiovascular risk factors.

PMID- 16414948
TI  - Long-term air pollution exposure and acceleration of atherosclerosis and vascular
      inflammation in an animal model.
AB  - CONTEXT: Recent studies have suggested a link between inhaled particulate matter
      exposure in urban areas and susceptibility to cardiovascular events; however, the
      precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis
      that subchronic exposure to environmentally relevant particulate matter, even at
      low concentrations, potentiates atherosclerosis and alters vasomotor tone in a
      susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21,
      2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on
      randomized assignments, fed with normal chow or high-fat chow and exposed to
      concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air
      (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months.
      MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and
      abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group,
      the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2%
      (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque
      area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in
      the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in
      mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0];
      95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to
      phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat
      chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean
      [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs
      125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium
      dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose
      for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04).
      Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in
      macrophage infiltration, expression of the inducible isoform of nitric oxide
      synthase, increased generation of reactive oxygen species, and greater
      immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001).
      CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of
      PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated
      atherosclerosis.

PMID- 16414949
TI  - Medical and legal issues in the cardiovascular evaluation of competitive
      athletes.
AB  - Healthy-appearing competitive athletes may harbor unsuspected cardiovascular
      disease with the potential to cause sudden death. This fact raises issues of
      physician responsibility in preparticipation screening and
      eligibility/disqualification decisions. A number of medical-legal cases now
      represent a framework for screening and eligibility decision making in high
      school and college athletes. Physicians screening competitive athletes should
      strictly adhere to recommendations from the American Heart Association. Precedent
      exists for disqualifying athletes with heart disease from competition to prevent
      unnecessary exposure to risk of injury or death. By virtue of the court decision
      in Larkin v Archdiocese of Cincinnati, high school students with heart disease
      have no compelling right to participate in interscholastic sports without medical
      clearance. In Knapp v Northwestern University, an appellate court ruled that
      college athletes can be medically disqualified from sports and supported the use
      of national association medical guidelines by team physicians in formulating
      eligibility/disqualification decisions. This medical-legal analysis provides
      guidelines for physicians participating in medical evaluations of competitive
      athletes by clarifying the standard of care, potential pitfalls, and the evolving
      liability associated with this clinical practice.

PMID- 16414950
TI  - Immunological memory: the role of B cells in long-term protection against
      invasive bacterial pathogens.
AB  - Protein-polysaccharide conjugate vaccines that protect against Haemophilus
      influenzae type b (Hib), serogroup C Neisseria meningitidis, and multiple
      capsular serotypes of Streptococcus pneumoniae have had a major impact on
      invasive bacterial disease in childhood when incorporated into routine infant
      immunization schedules. However, effectiveness data from the United Kingdom
      suggest that primary infant immunization alone may not be associated with long
      term protection. Both immunological priming and antibody persistence are
      important aspects of long-term protection induced by these vaccines. An improved
      understanding of the immunobiology of the B-cell response to these vaccines may
      direct development of immunization strategies that provide sustained protection.

PMID- 16414951
TI  - On the preservation of health.

PMID- 16414952
TI  - Efficient genotyping for congenital long QT syndrome.

PMID- 16414953
TI  - JAMA patient page. Fitness.

PMID- 16414954
TI  - A novel strategy for the identification of genomic islands by comparative
      analysis of the contents and contexts of tRNA sites in closely related bacteria.
AB  - We devised software tools to systematically investigate the contents and contexts
      of bacterial tRNA and tmRNA genes, which are known insertion hotspots for genomic
      islands (GIs). The strategy, based on MAUVE-facilitated multigenome comparisons,
      was used to examine 87 Escherichia coli MG1655 tRNA and tmRNA genes and their
      orthologues in E.coli EDL933, E.coli CFT073 and Shigella flexneri Sf301. Our
      approach identified 49 GIs occupying approximately 1.7 Mb that mapped to 18 tRNA
      genes, missing 2 but identifying a further 30 GIs as compared with Islander [Y.
      Mantri and K. P. Williams (2004), Nucleic Acids Res., 32, D55-D58]. All these GIs
      had many strain-specific CDS, anomalous GC contents and/or significant
      dinucleotide biases, consistent with foreign origins. Our analysis demonstrated
      marked conservation of sequences flanking both empty tRNA sites and tRNA
      associated GIs across all four genomes. Remarkably, there were only 2 upstream
      and 5 downstream deletions adjacent to the 328 loci investigated. In silico PCR
      analysis based on conserved flanking regions was also used to interrogate
      hotspots in another eight completely or partially sequenced E.coli and Shigella
      genomes. The tools developed are ideal for the analysis of other bacterial
      species and will lead to in silico and experimental discovery of new genomic
      islands.

PMID- 16414956
TI  - Structural and dynamic basis of a supercoiling-responsive DNA element.
AB  - In both eukaryotes and prokaryotes, negative supercoiling of chromosomal DNA acts
      locally to regulate a variety of cellular processes, such as transcription,
      replication, recombination and response to environmental stresses. While studying
      the interaction between the Hin recombinase and mutated versions of its cognate
      DNA-binding site, we identified a mutated DNA site that binds Hin only when the
      DNA is supercoiled. To understand the mechanism of this supercoiling-responsive
      DNA site, we used NMR spectroscopy and fluorescence resonance energy transfer to
      determine the solution structures and dynamics of three related DNA
      oligonucleotides. The supercoiling-responsive DNA site formed a partially unwound
      and stretched helix and showed significant flexibility and base pair opening
      kinetics. The single CAG/CTG triplet contained in this DNA sequence displayed the
      same characteristics as do multiple CAG/CTG repeats, which are associated with
      several hereditary neuromuscular diseases. It is known that short DNA sequence
      motifs that have either very high or low bending flexibility occur preferentially
      at supercoiling-sensitive bacterial and eukaryotic promoters. From our results
      and these previous data, we propose a model in which supercoiling utilizes the
      intrinsic flexibility of a short DNA site to switch the local DNA structure from
      an inefficient conformation for protein binding to an efficient one, or vice
      versa.

PMID- 16414955
TI  - Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA
      generate an unusually long 3'-UTR.
AB  - Adducins are a family of membrane skeleton proteins composed of alpha-, beta- and
      gamma-subunits that promote actin and spectrin association in erythrocytes. The
      alpha- and gamma-subunits are expressed ubiquitously, while the beta-subunit is
      found in brain and erythropoietic tissues. The brain beta-adducin protein is
      similar in size to that of spleen, but the mRNA transcript is a brain-specific
      one that has not been yet characterized, having an estimated length of 8-9 kb
      instead of the 3-4 kb of spleen mRNA. Here, we show the molecular basis for these
      differences by determining the structure of the brain-specific beta-adducin
      transcript in rats, mice and humans. We identified a brain-specific promoter in
      rodents that, apparently, was not conserved in humans. In addition, we present
      evidence that the brain-mRNAs are formed by a common mechanism consisting in the
      tissue-specific use of alternative polyadenylation sites generating unusually
      long 3'-untranslated region of up to 6.6 kb. This hypothesis is supported by the
      presence of highly-conserved regions flanking the brain-specific polyadenylation
      site that suggest the involvement of these sequences in the translational
      regulation, stability and/or subcellular localization of the beta-adducin
      transcript in the brain.

PMID- 16414957
TI  - Active conformation of the erythropoietin receptor: random and cysteine-scanning
      mutagenesis of the extracellular juxtamembrane and transmembrane domains.
AB  - In the absence of erythropoietin (Epo) cell surface Epo receptors (EpoR) are
      dimeric; dimerization is mediated mainly by the transmembrane domain. Binding of
      Epo changes the orientation of the two receptor subunits. This conformational
      change is transmitted through the juxtamembrane and transmembrane domains,
      leading to activation of JAK2 kinase and induction of proliferation and survival
      signals. To define the active EpoR conformation(s) we screened libraries of EpoRs
      with random mutations in the transmembrane domain and identified several point
      mutations that activate the EpoR in the absence of ligand, including changes of
      either of the first two transmembrane domain residues (Leu(226) and Ile(227)) to
      cysteine. Following this discovery, we performed cysteine-scanning mutagenesis in
      the EpoR juxtamembrane and transmembrane domains. Many mutants formed disulfide
      linked receptor dimers, but only EpoR dimers linked by cysteines at positions
      223, 226, or 227 activated EpoR signal transduction pathways and supported
      proliferation of Ba/F3 cells in the absence of cytokines. These data suggest that
      activation of dimeric EpoR by Epo binding is achieved by reorienting the EpoR
      transmembrane and the connected cytosolic domains and that certain disulfide
      bonded dimers represent the activated dimeric conformation of the EpoR,
      constitutively activating downstream signaling. Based on our data and the
      previously determined structure of Epo bound to a dimer of the EpoR extracellular
      domain, we present a model of the active and inactive conformations of the Epo
      receptor.

PMID- 16414958
TI  - The outer membrane protein OmpW forms an eight-stranded beta-barrel with a
      hydrophobic channel.
AB  - Escherichia coli OmpW belongs to a family of small outer membrane proteins that
      are widespread in Gram-negative bacteria. Their functions are unknown, but recent
      data suggest that they may be involved in the protection of bacteria against
      various forms of environmental stress. To gain insight into the function of these
      proteins A we have determined the crystal structure of E. coli OmpW to 2.7-A
      resolution. The structure shows that OmpW forms an 8-stranded beta-barrel with a
      long and narrow hydrophobic channel that contains a bound n-dodecyl-N,N
      dimethylamine-N-oxide detergent molecule. Single channel conductance experiments
      show that OmpW functions as an ion channel in planar lipid bilayers. The channel
      activity can be blocked by the addition of n-dodecyl-N,N-dimethylamine-N-oxide.
      Taken together, the data suggest that members of the OmpW family could be
      involved in the transport of small hydrophobic molecules across the bacterial
      outer membrane.

PMID- 16414959
TI  - Tocopherol cyclase (VTE1) localization and vitamin E accumulation in chloroplast
      plastoglobule lipoprotein particles.
AB  - Chloroplasts contain lipoprotein particles termed plastoglobules. Plastoglobules
      are generally believed to have little function beyond lipid storage. Here we
      report on the identification of plastoglobule proteins using mass spectrometry
      methods in Arabidopsis thaliana. We demonstrate specific plastoglobule
      association of members of the plastid lipid-associated proteins/fibrillin family
      as well as known metabolic enzymes, including the tocopherol cyclase (VTE1), a
      key enzyme of tocopherol (vitamin E) synthesis. Moreover, comparative analysis of
      chloroplast membrane fractions shows that plastoglobules are a site of vitamin E
      accumulation in chloroplasts. Thus, in addition to their lipid storage function,
      we propose that plastoglobules are metabolically active, taking part in
      tocopherol synthesis and likely other pathways.

PMID- 16414960
TI  - Mechanistic analysis of a multiple product sterol methyltransferase implicated in
      ergosterol biosynthesis in Trypanosoma brucei.
AB  - Sterol methyltransferase (SMT) plays a key role in sterol biosynthesis in
      different pathogenic organisms by setting the pattern of the side chain structure
      of the final product. This catalyst, absent in humans, provides critical pathway
      specific enzymatic steps in the production of ergosterol in fungi or phytosterols
      in plants. The new SMT gene was isolated from Trypanosoma brucei genomic DNA and
      cloned into an Escherichia coli expression system. The recombinant SMT was
      purified to homogeneity to give a band at 40.0 kDa upon SDS-PAGE and showed a
      tetrameric subunit organization by gel chromatography. It has a pH optimum of
      7.5, an apparent kcat value of 0.01 s(-1), and a Km of 47 +/- 4 microm for
      zymosterol. The products of the reaction were a mixture of C24-monoalkylated
      sterols, ergosta-8,24 (25)-dienol, ergosta-8,25 (27)-dienol, and ergosta-8,24
      (28)-dienol (fecosterol), and an unusual double C24-alkylated sterol, 24,24
      dimethyl ergosta-8,25 (27)-dienol, typically found in plants. Inhibitory profile
      studies with 25-azalanosterol (Ki value of 39 nm) or 24(R,S), 25
      epiminolanosterol (Ki value of 49 nm), ergosterol (Ki value of 27 microm) and
      26,27-dehydrozymosterol (Ki and kinact values of 29 microm and 0.26 min(-1),
      respectively) and data showing zymosterol as the preferred acceptor strongly
      suggest that the protozoan SMT has an active site topography combining properties
      of the SMT1 from plants and yeast (37-47% identity). The enzymatic activation of
      this and other SMTs reveals that the catalytic requirements for the C-methyl
      reaction are remarkably versatile, whereas the inhibition studies provide a
      powerful approach to rational design of new anti-sleeping sickness
      chemotherapeutic drugs.

PMID- 16414961
TI  - Multiple association analysis via simulated annealing (MASSA).
AB  - SUMMARY: Genome-wide association studies are now technically feasible and likely
      to become a fundamental tool in unraveling the ultimate genetic basis of complex
      traits. However, new statistical and computational methods need to be developed
      to extract the maximum information in a realistic computing time. Here we propose
      a new method for multiple association analysis via simulated annealing that
      allows for epistasis and any number of markers. It consists of finding the model
      with lowest Bayesian information criterion using simulated annealing. The data
      are described by means of a mixed model and new alternative models are proposed
      using a set of rules, e.g. new sites can be added (or deleted), or new epistatic
      interactions can be included between existing genetic factors. The method is
      illustrated with simulated and real data. AVAILABILITY: An executable version of
      the program (MASSA) running under the Linux OS is freely available, together with
      documentation, at http://www.icrea.es/pag.asp?id=Miguel.Perez.

PMID- 16414962
TI  - Living wills and the Mental Capacity Act: a postal questionnaire survey of UK
      geriatricians.
AB  - OBJECTIVE: To determine geriatricians' experience of and views on living wills,
      National Health Service Trusts' support of advance end-of-life health care
      planning and geriatricians' views on related legal changes in the Mental Capacity
      Act. DESIGN: Anonymous postal questionnaire survey of all 1,426 British
      Geriatrics Society members in England, Wales and Northern Ireland. RESULTS: A
      total of 842 (59%) questionnaires were returned. Of 811 geriatricians, 454 (56%)
      had cared for patients with living wills. Of the 280 who cared for patients when
      the living will had come into effect, 108 (39%) had changed treatment because of
      the living will and 84 (78%) of those felt that decisions had been easier to
      make. Living wills not already in effect made discussions with patients [171 of
      178 (96%)] and families [135 of 178 (76%)] easier. Of 779 geriatricians, 713
      (92%) saw advantages of older people using living wills; 467 of these also
      expressed concerns. Only 16 (2%) geriatricians who had concerns said that there
      were no advantages. A total of 214 (27%) were aware that their Trust had a form
      to help with discussions about cardiopulmonary resuscitation. Fewer [126 of 781
      (16%)] were aware of a Trust policy on living wills. The proposal, in the Mental
      Capacity Bill, for advance refusals of treatment was supported by 59% (476 of
      801), yet the proposal for a lasting power of attorney (LPA) covering health care
      was only supported by 47% (382 of 806). CONCLUSION: Many geriatricians have
      positive experiences of caring for patients with living wills. Despite
      recognising potential problems, most geriatricians support the use of living
      wills by older people. However, most believe that their Trust does not have a
      policy to support advance health care planning. Geriatricians have reservations
      about LPAs covering health care.

PMID- 16414963
TI  - Death with dementia--the need for better care.

PMID- 16414965
TI  - Juvenile myoclonic epilepsy in an elderly patient.
AB  - Juvenile myoclonic epilepsy constitutes 5-10% of idiopathic generalised epileptic
      syndromes. The clinical triad of absence seizures, myoclonic jerks and
      generalised tonic clonic seizures (GTCS) rarely begin after the second decade of
      life. We present the case of a 74-year-old lady presenting for the first time
      with myoclonic jerks and absences. The electro encephalogram revealed generalised
      polyspike and wave epileptiform activity with photosensitivity. On close
      questioning, she appeared to have had a single episode of GTCS at the age of 10.
      She remained asymptomatic for 64 years before the diagnosis was made. Although
      rare, idiopathic myoclonic epilepsy could remain asymptomatic for decades and can
      present in the elderly. Proper classification of this epileptic syndrome, even in
      the elderly, is essential in view of the response to appropriate antiepileptic
      therapy.

PMID- 16414966
TI  - Therapeutic failure of cinacalcet in a renal transplant patient.

PMID- 16414964
TI  - Risk factors for incident dementia in England and Wales: The Medical Research
      Council Cognitive Function and Ageing Study. A population-based nested case
      control study.
AB  - OBJECTIVE: To investigate a number of prospectively collected factors
      (sociodemographic, medical and behavioural) and their association with incident
      dementia in a population-based cohort. DESIGN: Nested case-control analysis (at 2
      and 6 years) of a population-based cohort study. SETTING: Individuals aged 65
      years and above from five centres in England and Wales: two rural (Cambridgeshire
      and Gwynedd) and three urban (Nottingham, Newcastle and Oxford). PARTICIPANTS: A
      total of 4,075 individuals from a detailed assessment group, with risk measured
      at baseline. MAIN OUTCOME MEASURE: Incident dementia at 2 and 6 years. METHODS:
      Logistic regression was used to calculate crude odds ratios (ORs) for various
      risk factors and ORs adjusted for age, sex, education and social class. RESULTS:
      Age (90+ versus 65-69 years OR = 25.6, 95% confidence interval (CI) = 11.6-56.9)
      and sex (women versus men OR = 1.6, 95% CI = 1.1-2.4) were directly associated
      with dementia, with a trend by years of education (P(trend) = 0.02) but not
      social class. Poor self-perceived health (versus good) increased the risk for
      incident dementia (OR = 3.9, 95% CI = 2.2-6.9). Alcohol and smoking (never, past
      and current) were neither strongly protective nor predictive. Stroke was strongly
      related to incident dementia (OR = 2.1, 95% CI = 1.1-4.2), as was Parkinson's
      disease (OR = 3.5, 95% CI = 1.3-9.3), and exposure to general anaesthesia (GA)
      was inversely associated with dementia development (OR = 0.6, 95% CI = 0.4-0.9,
      with a trend with increasing GA exposure; P = 0.003). CONCLUSION: In this large
      multicentre and long-term population-based study, some well-known risk factors
      for dementia, of vascular and Alzheimer's type, are confirmed but not others. The
      association between self-perceived health-a robust predictor of later health
      outcomes-and incident dementia, independently of other potential risks, warrants
      further study.

PMID- 16414967
TI  - An accident with Tenckhoff catheter placement: urinary bladder perforation.

PMID- 16414968
TI  - Do patients with older-onset rheumatoid arthritis receive less aggressive
      treatment?
AB  - Rheumatoid arthritis among elderly people is an increasingly important health
      concern. Despite several cross-sectional studies, it has not been clearly
      established whether there are important clinical differences between elderly
      onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA).
      The aim of this study was to compare disease activity and treatment in EORA and
      YORA, using the Consortium of Rheumatology Researchers of North America (CORRONA)
      registry, a database generated by rheumatologist investigators across the USA.
      From the CORRONA registry database of 9381 patients with rheumatoid arthritis,
      2101 patients with disease onset after the age of 60 years (EORA) were matched,
      on the basis of disease duration, with 2101 patients with disease onset between
      the ages of 40 and 60 years (YORA). The primary outcome measures were the
      proportion of patients on methotrexate, multiple disease-modifying antirheumatic
      drugs (DMARD) and biological agents (etanercept, infliximab, adalimumab and
      kineret) in each group. Disease activity and severity differed slightly between
      the EORA and YORA groups: Disability Index of the Health Assessment
      Questionnaire: 0.30 v 0.35; tender joint count: 3.7 v 4.7; swollen joint count:
      5.3 v 5.2; Disease Activity Score 28: 3.8 v 3.6; patient global assessment: 29.1
      v 30.9; physician global assessment: 24.9 v 26.3; patient pain assessment: 31.4 v
      34.9. Regarding treatment, the use of methotrexate use was slightly more common
      among patients with EORA (63.9%) than among those with YORA (59.6%), although the
      mean methotrexate dose among the YORA group was higher than that in the EORA
      group. The percentage of patients with EORA who were on multiple DMARD treatment
      (30.9%) or on biological agents (25%) was considerably lower than that of
      patients with YORA (40.5% and 33.1%, respectively; p<0.0001). Toxicity related to
      treatment was very minimal in both groups, whereas toxicities related to
      methotrexate were more common in the YORA group. Patients with EORA receive
      biological treatment and combination DMARD treatment less frequently than those
      with YORA, despite identical disease duration and comparable disease severity and
      activity.

PMID- 16414969
TI  - Synovial inflammation does not change in the absence of effective treatment:
      implications for the use of synovial histopathology as biomarker in early phase
      clinical trials in rheumatoid arthritis.
AB  - OBJECTIVES: To determine the impact on synovial histopathology of changes in
      clinical disease activity in the absence of effective treatment. METHODS: Twelve
      patients with active RA not receiving effective treatment were studied over a 14
      week period. Synovial biopsy specimens obtained at baseline and week 14 were
      analysed by histology and immunohistochemistry. RESULTS: Over the course of 14
      weeks, there was a trend towards a decrease of the DAS28, with 7/12 patients
      being good or moderate DAS28 responders despite the absence of effective
      treatment. Patients' assessment of global disease activity and swollen joint
      count both decreased significantly. Histologically, there was a decrease of
      lining layer hyperplasia and lymphoid aggregates, a similar trend for
      vascularity, but there was no effect on global synovial infiltration.
      Accordingly, there was no decrease of the cellular infiltration with T
      lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), plasma cells (CD38), dendritic
      cells (CD1a, CD83), and even an increase of CD163+ sublining macrophages, with a
      similar trend for CD68+ sublining macrophages. The changes in DAS28 scores in
      these patients did not correlate with changes in histological variables, with the
      exception of an inverse correlation with plasma cells. Remarkably, even in the
      DAS28 responders, no significant changes in synovial inflammatory infiltration
      were noted. CONCLUSIONS: Despite variations in global disease activity, synovial
      inflammatory infiltration did not change significantly in the absence of
      effective treatment. The lack of a placebo effect on synovial markers of
      treatment response such as sublining macrophages can facilitate conclusive early
      phase trials with small numbers of patients with RA.

PMID- 16414970
TI  - Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case
      control study.
AB  - BACKGROUND: Several inflammatory conditions are associated with an increased risk
      of lymphoma. The specific features of inflammation that mediate this risk are
      unknown. There are few studies on whether ankylosing spondylitis increases the
      risk of lymphoma. Besides inflammation-lymphoma aetiology, information on risk of
      lymphoma in ankylosing spondylitis is particularly important as a benchmark in
      the evaluation of, for example, tumour necrosis factor inhibitors. METHODS: The
      association between ankylosing spondylitis and malignant lymphomas overall, and
      separately for non-Hodgkin's lymphoma, Hodgkin's lymphoma and chronic lymphocytic
      leukaemia, was assessed in a nationwide, population-based case-control study of
      50 615 cases of lymphoma and 92 928 matched controls by using prospectively
      recorded data on lymphomas from the Swedish Cancer Register (1964-2000) and data
      on pre-lymphoma hospitalisations for ankylosing spondylitis from the Swedish
      Inpatient Register (1964-2000). The odds ratios (ORs) associated with pre
      lymphoma hospitalisation for ankylosing spondylitis were calculated using
      conditional logistic regression. RESULTS: 23 (0.05%) patients with lymphoma and
      41 (0.05%) controls had a pre-lymphoma hospitalisation listing ankylosing
      spondylitis, relative risk = 1.0 (95% confidence interval (CI) 0.6 to 1.7). The
      number of discharges and the mean latency between ankylosing spondylitis and
      lymphoma were similar in patients and controls. Analyses restricted to lymphomas
      diagnosed during the 1990s showed similar results (OR = 1.3, 95% CI 0.6 to 2.5,
      number of exposed cases/controls = 14/21). CONCLUSIONS: On average and in the
      absence of tumour necrosis factor inhibitors, patients hospitalised with
      ankylosing spondylitis do not appreciably show an increased risk of lymphoma.

PMID- 16414971
TI  - Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the
      United Kingdom, 1990-2001.
AB  - OBJECTIVE: To investigate time trends, geographical variation, and seasonality in
      the incidence of diagnosis of polymyalgia rheumatica (PMR) and temporal arteritis
      (TA) in the United Kingdom. METHODS: Analysis of computerised medical records
      from UK general practices. Participants were registered with a practice
      contributing to the General Practice Research Database during the period 1990
      2001. The main outcome measures were rates of diagnosis by year, age, sex,
      geographical region, and calendar month. RESULTS: 15 013 people had a first
      diagnosis of PMR and 3928 a first diagnosis of TA during 17 830 028 person-years
      of observation. The age adjusted incidence rate of PMR was 8.4/10 000 person
      years (95% CI 8.3 to 8.6), rising from 6.9/10 000 person-years in 1990 to 9.3/10
      000 in 2001. The age adjusted incidence rate of TA was 2.2/10 000 person-years
      (95% CI 2.1 to 2.3) with no increase observed. Both PMR and TA were more common
      in the south than in the north of the UK, and both were more commonly diagnosed
      in the summer months. CONCLUSIONS: The explanation for the findings is unclear.
      Variations in diagnostic practice and accuracy are likely to have contributed in
      part to the patterns seen. However, the findings are also likely to reflect, at
      least in part, variations in the incidence of disease. The striking geographical
      pattern may be partly attributable to a risk factor which is more prevalent in
      the south and east of the United Kingdom.

PMID- 16414972
TI  - Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin
      and visfatin in patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is a chronic autoimmune inflammatory condition
      characterised by polyarthritis and severe change in body mass and neuroendocrine
      environment. OBJECTIVES: To investigate plasma levels of adipocytokines (leptin,
      adiponectin, visfatin and resistin) in patients with rheumatoid arthritis and to
      compare them with levels in healthy controls. METHODS: Adiponectin, resistin,
      visfatin and leptin concentrations were measured in 31 patients with rheumatoid
      arthritis and 18 healthy controls by using specific enzyme-linked immunosorbent
      assays. RESULTS: Patients with rheumatoid arthritis showed considerably higher
      plasma levels of leptin, adiponectin and visfatin than healthy controls. No
      marked difference was observed in resistin levels between patients and controls.
      CONCLUSION: A marked increase in plasma levels of leptin, adiponectin and
      visfatin was noted in patients with rheumatoid arthritis, whereas resistin levels
      were similar to those observed in healthy controls. Coordinated roles for
      adiponectin, leptin and visfatin are suggested in the modulation of the
      inflammatory environment in patients with rheumatoid arthritis, whereas the lack
      of modulation in resistin levels is predictive of an irrelevant role for this
      peptide, suggesting that resistin level is probably not one of the main signals
      associated with the pathogenesis of this disease.

PMID- 16414973
TI  - Distinct recognition of antibodies to centromere proteins in primary Sjogren's
      syndrome compared with limited scleroderma.
AB  - BACKGROUND: Anticentromere antibodies are characteristically observed in
      scleroderma but have recently been reported in other autoimmune rheumatic
      disorders, including Sjogren's syndrome. It is not known whether distinct
      centromere proteins (CENP) are targeted in primary Sjogren's syndrome (pSS) and
      scleroderma. OBJECTIVE: To determine whether antibodies to CENP-B and CENP-C are
      present in these two disorders. METHODS: Sera from 45 patients with pSS and 33
      with limited scleroderma were studied. All patients met classification criteria
      for pSS and scleroderma, respectively. Sera were used to immunoprecipitate in
      vitro translated CENP-B and CENP-C. The proportions recognising CENP-B or CENP-C
      were compared. RESULTS: 10 of 45 patients (22%) with pSS and 18 of 33 (55%) with
      scleroderma had antibodies recognising CENPs (p = 0.004). Seven of 10 (70%) CENP
      positive patients with pSS recognised CENP-C alone, compared with one of 18 (6%)
      CENP positive patients with scleroderma (odds ratio (OR) = 40 (95% confidence
      interval (CI), 3.5 to 450) (p = 0.003). In contrast, the majority (15 of 18
      (83%)) of CENP positive scleroderma sera recognised both CENP-B and CENP-C,
      compared with none of 10 pSS sera (OR = 93 (95% CI, 4.4 to 1979) (p = 0.0001).
      CONCLUSIONS: The pattern of CENP recognition differs markedly in pSS and limited
      scleroderma. While patients with pSS predominantly recognise CENP-C alone, dual
      recognition of CENP-B and CENP-C is most frequent in scleroderma. These findings
      suggest that obtaining antibodies to specific centromere antigens is useful
      diagnostically, and imply that distinct mechanisms underlie the unique patterns
      of centromere autoreactivity in pSS and scleroderma.

PMID- 16414974
TI  - Immunoproteasome subunit LMP2 expression is deregulated in Sjogren's syndrome but
      not in other autoimmune disorders.
AB  - BACKGROUND: The proteasome system has a pivotal role in the control of the immune
      response, which suggests that it might be involved in the pathogenesis of
      autoimmune disorders. OBJECTIVE: To investigate the expression profile of
      selected proteasomal genes in human peripheral blood mononuclear cells in
      patients with a variety of autoimmune diseases compared with healthy subjects.
      METHODS: Real time quantitative RT-PCR was used to analyse the mRNA expression
      pattern of the proteasome activator subunits PA28alpha and PA28beta and of
      constitutive proteasome and interferon-gamma-inducible immunoproteasome subunits
      in peripheral blood mononuclear cells. Simultaneously, protein expression of
      selected proteasome subunits was quantified by immunoblotting. RESULTS: Under
      systemic inflammatory conditions the proteasome subunits LMP2 (beta1i), LMP7
      (beta5i), MECL1 (beta2i), and PA28alpha were expressed abundantly at the protein
      level in the vast majority of systemic autoimmune disorders. However,
      simultaneous mRNA and protein quantification showed a characteristic proteasome
      expression signature in primary Sjogren's syndrome. At the transcript level, the
      interferon-gamma-responsive subunits LMP2 (beta1i), MECL1 (beta2i), and the
      proteasome activator subunit PA28alpha were markedly up regulated. In contrast,
      LMP2 (beta1i) deficiency was evident at the protein level, indicating
      deregulation of proteasome expression in Sjogren's syndrome. CONCLUSIONS: These
      data provide evidence for a regulatory defect in the proteasome system in human
      autoimmune disorders, pointing to a unique role for LMP2 (beta1i) in the
      pathogenesis of primary Sjogren's syndrome.

PMID- 16414975
TI  - Swedish registers to examine drug safety and clinical issues in RA.
AB  - Data from several different monitoring systems are examined. The potential for
      registers based on data obtained from clinical practice, and linkage of such data
      to national health and population registers, is discussed. The approach described
      is a possible prototype for long term surveillance systems needed for the safe
      introduction of new treatments.

PMID- 16414976
TI  - Radiological hand involvement in systemic sclerosis.
AB  - BACKGROUND: The osteoarticular and soft tissue structures of the hand may be
      involved in systemic sclerosis (SSc), causing functional disability. OBJECTIVE:
      To assess radiological hand features in a cross sectional study of SSc patients
      and in controls. METHODS: Hand radiology was done systematically in patients with
      SSc seen over a two year period and in unselected controls with rheumatoid
      arthritis or digital trauma. Two independent investigators blind to the diagnosis
      carried out the radiological assessment. RESULTS: 120 consecutive SSc patients
      (median (range) age, 56.5 (20 to 90) years; disease duration, 6 (0 to 42) years)
      and 42 controls (22 with rheumatoid arthritis and 20 with digital trauma) were
      studied. Radiological abnormalities in SSc patients included erosion (21%), joint
      space narrowing (28%), arthritis (defined by concomitant erosion and joint space
      narrowing) (18%), radiological demineralisation (23%), acro-osteolysis (22%),
      flexion contracture (27%), and calcinosis (23%). In univariate and multivariate
      analysis, the resorption of distal phalanges was significantly associated with
      digital ulcers, extra-articular calcification, and pulmonary arterial
      hypertension; flexion contracture was associated with the diffuse cutaneous form
      and high HAQ (Health Assessment Questionnaire) disability score. Calcinosis was
      most often seen in patients with digital ulcers, but was similarly observed in
      patients with the diffuse or limited cutaneous subtypes. CONCLUSIONS: Flexion
      contracture was associated with disability and occurred in patients with the
      diffuse cutaneous subtype of SSc, consistent with the tendency towards fibrosis
      and functional impairment of this subtype. Calcinosis and acro-osteolysis were
      both associated with vascular complications, highlighting a potential role of
      vascular injury in such lesions.

PMID- 16414977
TI  - Discordant regulatory changes in monocrotaline-induced megalocytosis of lung
      arterial endothelial and alveolar epithelial cells.
AB  - Monocrotaline (MCT) causes pulmonary hypertension in the rat by a mechanism
      characterized by megalocytosis (enlarged cells with enlarged endoplasmic
      reticulum and Golgi and a cell cycle arrest) of pulmonary arterial endothelial
      (PAEC), arterial smooth muscle, and type II alveolar epithelial cells. In cell
      culture, although megalocytosis is associated with a block in entry into mitosis
      in both lung endothelial and epithelial cells, DNA synthesis is stimulated in
      endothelial but inhibited in epithelial cells. The molecular mechanism(s) for
      this dichotomy are unclear. While MCTP-treated PAEC and lung epithelial (A549)
      cells both showed an increase in the "promitogenic" transcription factor STAT3
      levels and in the IL-6-induced nuclear pool of PY-STAT3, this was
      transcriptionally inactive in A549 but not in PAEC cells. This lack of
      transcriptional activity of STAT3 in A549 cells correlated with the cytoplasmic
      sequestration of the STAT3 coactivators CBP/p300 and SRC1/NcoA in A549 cells but
      not in PAEC. Both cell types displayed a Golgi trafficking block, loss of
      caveolin-1 rafts, and increased nuclear Ire1alpha, but an incomplete unfolded
      protein response (UPR) with little change in levels of UPR-induced chaperones
      including GRP78/BiP. There were discordant alterations in cell cycle regulatory
      proteins in the two cell types such as increase in levels of both cyclin D1 and
      p21 simultaneously, but with a decrease in cdc2/cdk1, a kinase required for entry
      into mitosis. While both cell types showed increased cytoplasmic geminin, the DNA
      synthesis-initiating protein Cdt1 was predominantly nuclear in PAEC but remained
      cytoplasmic in A549 cells, consistent with the stimulation of DNA synthesis in
      the former but an inhibition in the latter cell type. Thus differences in cell
      type-specific alterations in subcellular trafficking of critical regulatory
      molecules (such as CBP/p300, SRC1/NcoA, Cdt1) likely account for the dichotomy of
      the effects of MCTP on DNA synthesis in endothelial and epithelial cells.

PMID- 16414979
TI  - Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial
      cells in vivo.
AB  - Habitual marijuana smoking is associated with inflammation and atypia of airway
      epithelium accompanied by symptoms of chronic bronchitis. We hypothesized that
      Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive component of
      marijuana, might contribute to these findings by impairing cellular energetics
      and mitochondrial function. To test this hypothesis, we examined particulate
      smoke extracts from marijuana cigarettes, tobacco cigarettes, and placebo
      marijuana (0% THC) cigarettes for their effects on the mitochondrial function of
      A549 cells in vitro. Only extracts prepared from marijuana cigarettes altered
      mitochondrial staining by the potentiometric probe JC-1. With the use of a cross
      flow, nose-only inhalation system, rats were then exposed for 20 min to whole
      marijuana smoke and examined for its effects on airway epithelial cells.
      Inhalation of marijuana smoke produced lung tissue concentrations of THC that
      were 8-10 times higher than those measured in blood (75 +/- 38 ng/g wet wt tissue
      vs. 9.2 +/- 2.0 ng/ml), suggesting high local exposure. Intratracheal infusion of
      JC-1 immediately following marijuana smoke exposure revealed a diffuse decrease
      in lung cell JC-1 red fluorescence compared with tissue from unexposed or placebo
      smoke-exposed rats. Exposure to marijuana smoke in vivo also decreased JC-1 red
      fluorescence (54% decrease, P < 0.01) and ATP levels (75% decrease, P < 0.01) in
      single-cell preparations of tracheal epithelial cells. These results suggest that
      inhalation of marijuana smoke has deleterious effects on airway epithelial cell
      energetics that may contribute to the adverse pulmonary consequences of marijuana
      smoking.

PMID- 16414978
TI  - Streptococcus pneumoniae induced p38 MAPK- and NF-kappaB-dependent COX-2
      expression in human lung epithelium.
AB  - Streptococcus pneumoniae is a major cause of community-acquired pneumonia and
      death from infectious diseases in industrialized countries. Lung airway and
      alveolar epithelial cells comprise an important barrier against airborne
      pathogens. Cyclooxygenase (COX)-derived prostaglandins, such as PGE(2), are
      considered to be important regulators of lung function. Herein, we tested the
      hypothesis that pneumococci induced COX-2-dependent PGE(2) production in
      pulmonary epithelial cells. Pneumococci-infected human pulmonary epithelial BEAS
      2B cells released PGE(2). Expression of COX-2 but not COX-1 was dose and time
      dependently increased in S. pneumoniae-infected BEAS-2B cells as well as in lungs
      of mice with pneumococcal pneumonia. S. pneumoniae induced degradation of
      IkappaBalpha and DNA binding of NF-kappaB. A specific peptide inhibitor of the
      IkappaBalpha kinase complex blocked pneumococci-induced PGE(2) release and COX-2
      expression. In addition, we noted activation of p38 MAPK and JNK in pneumococci
      infected BEAS-2B cells. PGE(2) release and COX-2 expression were reduced by p38
      MAPK inhibitor SB-202190 but not by JNK inhibitor SP-600125. We analyzed
      interaction of kinase pathways and NF-kappaB activation: dominant-negative
      mutants of p38 MAPK isoforms alpha, beta(2), gamma, and delta blocked S.
      pneumoniae-induced NF-kappaB activation. In addition, recruitment of NF-kappaB
      subunit p65/RelA and RNA polymerase II to the cox2 promoter depended on p38 MAPK
      but not on JNK activity. In summary, p38 MAPK- and NF-kappaB-controlled COX-2
      expression and subsequent PGE(2) release by lung epithelial cells may contribute
      significantly to the host response in pneumococcal pneumonia.

PMID- 16414980
TI  - Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue:
      roles of mechanical force and the cytoskeleton.
AB  - The viscoelastic and dynamic nonlinear properties of guinea pig tracheal smooth
      muscle tissues were investigated by measuring the storage (G') and loss (G")
      moduli using pseudorandom small-amplitude length oscillations between 0.12 and
      3.5 Hz superimposed on static strains of either 10 or 20% of initial length. The
      G" and G' spectra were interpreted using a linear viscoelastic model
      incorporating damping (G) and stiffness (H), respectively. Both G and H were
      elevated following an increase in strain from 10 to 20%. There was no change in
      harmonic distortion (K(d)), an index of dynamic nonlinearity, between 10 and 20%
      strains. Application of methacholine at 10% strain significantly increased G and
      H while it decreased K(d). Cytochalasin D, isoproterenol, and HA-1077, a Rho
      kinase inhibitor, significantly decreased both G and H but increased K(d).
      Following cytochalasin D, G, H, and K(d) were all elevated when mean strain
      increased from 10 to 20%. There were no changes in hysteresivity, G/H, under any
      condition. We conclude that not all aspects of the viscoelastic properties of
      tracheal smooth muscle strips are similar to those previously observed in
      cultured cells. We attribute these differences to the contribution of the
      extracellular matrix. Additionally, using a network model, we show that the
      dynamic nonlinear behavior, which has not been observed in cell culture, is
      associated with the state of the contractile stress and may derive from active
      polymerization within the cytoskeleton.

PMID- 16414981
TI  - Effects of macrophage inducible nitric oxide synthase in murine septic lung
      injury.
AB  - Inducible nitric oxide synthase (iNOS) contributes importantly to septic
      pulmonary protein leak in mice with septic acute lung injury (ALI). However, the
      role of alveolar macrophage (AM) iNOS in septic ALI is not known. Thus we
      assessed the specific effects of AM iNOS in murine septic ALI through selective
      AM depletion (via intratracheal instillation of clodronate liposomes) and
      subsequent AM reconstitution (via intratracheal instillation of donor iNOS+/+ or
      iNOS-/- AM). Sepsis was induced by cecal ligation and perforation, and ALI was
      assessed at 4 h: protein leak by the Evans blue (EB) dye method, neutrophil
      infiltration via myeloperoxidase (MPO) activity, and pulmonary iNOS mRNA
      expression via RT-PCR. In iNOS+/+ mice, AM depletion attenuated the sepsis
      induced increases in pulmonary microvascular protein leak (0.3 +/- 0.1 vs. 1.4 +/
      0.1 microg EB.g lung(-1).min(-1); P < 0.05) and MPO activity (37 +/- 4 vs. 67 +/
      8 U/g lung; P < 0.05) compared with that shown in non-AM-depleted mice. In AM
      depleted iNOS+/+ mice, septic pulmonary protein leak was restored by AM
      reconstitution with iNOS+/+ AM (0.9 +/- 0.3 microg EB.g lung(-1).min(-1)) but not
      with iNOS-/- donor AM. In iNOS-/- mice, sepsis did not induce pulmonary protein
      leak or iNOS mRNA expression, despite increased pulmonary MPO activity. However,
      AM depletion in iNOS-/- mice and subsequent reconstitution with iNOS+/+ donor AM
      resulted in significant sepsis-induced pulmonary protein leak and iNOS
      expression. Septic pulmonary MPO levels were similar in all AM-reconstituted
      groups. Thus septic pulmonary protein leak is absolutely dependent on the
      presence of functional AM and specifically on iNOS in AM. AM iNOS-dependent
      pulmonary protein leak was not mediated through changes in pulmonary neutrophil
      influx.

PMID- 16414982
TI  - Mechanism of fluoride-induced MAP kinase activation in pulmonary artery
      endothelial cells.
AB  - In this study, we demonstrate that challenge of endothelial cells (EC) with NaF,
      a recognized G protein activator and protein phosphatase inhibitor, leads to a
      significant Erk activation, with increased phosphorylation of the well-known Erk
      substrate caldesmon. Inhibition of the Erk MAPK, MEK, by U0126 produces a marked
      decrease in NaF-induced caldesmon phosphorylation. NaF transiently increases the
      activity of the MEK kinase known as Raf-1 (approximately 3- to 4-fold increase
      over basal level), followed by a sustained Raf-1 inhibition (approximately 3- to
      4-fold decrease). Selective Raf-1 inhibitors (ZM-336372 and Raf-1 inhibitor 1)
      significantly attenuate NaF-induced Erk and caldesmon phosphorylation. Because we
      have previously shown that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      participates in Erk activation in thrombin-challenged cells, we next explored if
      CaMKII is involved in NaF-induced EC responses. We found that in NaF-treated EC,
      CaMKII activity increases in a time-dependent manner with maximal activity at 10
      min (approximately 4-fold increase over a basal level). Pretreatment with KN93, a
      specific CaMKII inhibitor, attenuates NaF-induced barrier dysfunction and Erk
      phosphorylation. The Rho inhibitor C3 exotoxin completely abolishes NaF-induced
      CaMKII activation. Collectively, these data suggest that sequential activation of
      Raf-1, MEK, and Erk is modulated by Rho-dependent CaMKII activation and
      represents important NaF-induced signaling response. Caldesmon phosphorylation
      occurring by an Erk-dependent mechanism in NaF-treated pulmonary EC may represent
      a link between NaF stimulation and contractile responses of endothelium.

PMID- 16414983
TI  - Transforming growth factor-beta1 increases airway wound repair via MMP-2
      upregulation: a new pathway for epithelial wound repair?
AB  - In vivo, transforming growth factor (TGF)-beta1 and matrix metalloproteinases
      (MMPs) present at the site of airway injury are thought to contribute to
      epithelial wound repair. As TGF-beta1 can modulate MMP expression and MMPs play
      an important role in wound repair, we hypothesized that TGF-beta1 may enhance
      airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the
      in vitro influence of TGF-beta1 on wound repair in human airway epithelial cells
      cultured under conditions allowing differentiation. The results showed that TGF
      beta1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented
      this acceleration. In parallel, we examined the effect of TGF-beta1 on the
      expression of MMP-2 and MMP-9. TGF-beta1 induced a dramatic increase of MMP-2
      expression with an increased steady-state level of MMP-2 mRNA, contrasting with a
      slight increase in MMP-9 expression. To confirm the role of MMP-2, we
      subsequently evaluated the effect of MMP-2 on in vitro airway wound repair and
      demonstrated that the addition of MMP-2 reproduced the acceleration of wound
      repair induced by TGF-beta1. These results strongly suggest that TGF-beta1
      increases in vitro airway wound repair via MMP-2 upregulation. It also raises the
      issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the
      cytokine microenvironment.

PMID- 16414984
TI  - Role and mechanism of action of the APOBEC3 family of antiretroviral resistance
      factors.

PMID- 16414985
TI  - Identification of an NF-kappaB-dependent gene network in cells infected by
      mammalian reovirus.
AB  - Reovirus infection activates NF-kappaB, which leads to programmed cell death in
      cultured cells and in the murine central nervous system. However, little is known
      about how NF-kappaB elicits this cellular response. To identify host genes
      activated by NF-kappaB following reovirus infection, we used HeLa cells
      engineered to express a degradation-resistant mutant of IkappaBalpha
      (mIkappaBalpha) under the control of an inducible promoter. Induction of
      mIkappaBalpha inhibited the activation of NF-kappaB and blocked the expression of
      NF-kappaB-responsive genes. RNA extracted from infected and uninfected cells was
      used in high-density oligonucleotide microarrays to examine the expression of
      constitutively activated genes and reovirus-stimulated genes in the presence and
      absence of an intact NF-kappaB signaling axis. Comparison of the microarray
      profiles revealed that the expression of 176 genes was significantly altered in
      the presence of mIkappaBalpha. Of these genes, 64 were constitutive and not
      regulated by reovirus, and 112 were induced in response to reovirus infection. NF
      kappaB-regulated genes could be grouped into four distinct gene clusters that
      were temporally regulated. Gene ontology analysis identified biological processes
      that were significantly overrepresented in the reovirus-induced genes under NF
      kappaB control. These processes include the antiviral innate immune response,
      cell proliferation, response to DNA damage, and taxis. Comparison with previously
      identified NF-kappaB-dependent gene networks induced by other stimuli, including
      respiratory syncytial virus, Epstein-Barr virus, tumor necrosis factor alpha, and
      heart disease, revealed a number of common components, including CCL5/RANTES,
      CXCL1/GRO-alpha, TNFAIP3/A20, and interleukin-6. Together, these results suggest
      a genetic program for reovirus-induced apoptosis involving NF-kappaB-directed
      expression of cellular genes that activate death signaling pathways in infected
      cells.

PMID- 16414986
TI  - Bidirectional virus secretion and nonciliated cell tropism following Andes virus
      infection of primary airway epithelial cell cultures.
AB  - Hantavirus pulmonary syndrome (HPS) is an acute disease resulting from infection
      with any one of a number of New World hantaviruses. HPS has a mortality rate of
      40% and, unlike many other severe respiratory diseases, often occurs in young,
      healthy adults. Infection is usually initiated after inhalation of rodent excreta
      containing virus particles, but human-to-human transmission has been documented.
      Postmortem tissue samples show high levels of viral antigen within the
      respiratory endothelium, but it is not clear how the virus can traverse the
      respiratory epithelium in order to initiate infection in the microvasculature. We
      have utilized Andes virus infection of primary, differentiated airway epithelial
      cells to investigate the ability of the virus to interact with and cross the
      respiratory epithelium. Andes virus infects the Clara and goblet cell populations
      but not the ciliated cells, and this infection pattern corresponds to the
      expression of beta(3) integrin, the viral receptor. The virus can infect via the
      apical or basolateral membrane, and progeny virus particles are secreted
      bidirectionally. There is no obvious cytopathology associated with infection, and
      beta(3) integrins do not appear to be critical for respiratory epithelial cell
      monolayer integrity. Our data suggest that hantavirus infection of the
      respiratory epithelium may play an important role in the early or prodrome phase
      of disease as well as serving as a source of virus involved in transmission.

PMID- 16414987
TI  - Contribution of C/EBP proteins to Epstein-Barr virus lytic gene expression and
      replication in epithelial cells.
AB  - The contribution of C/EBP proteins to Epstein-Barr virus (EBV) lytic gene
      expression and replication in epithelial cells was examined. Nasopharyngeal
      carcinoma cell lines constitutively expressed C/EBPbeta and had limited
      C/EBPalpha expression, while the AGS gastric cancer cell line expressed
      significant levels of both C/EBPalpha and C/EBPbeta. Induction of the lytic cycle
      in EBV-positive AGS/BX1 cells with phorbol ester and sodium butyrate treatment
      led to a transient stimulation of C/EBPbeta expression and a prolonged increase
      in C/EBPalpha expression. In AGS/BX1 cells, endogenous C/EBPalpha and C/EBPbeta
      proteins were detected associated with the ZTA and oriLyt promoters but not the
      RTA promoter. Electrophoretic mobility shift assays confirmed binding of C/EBP
      proteins to multiple sites in the ZTA and oriLyt promoters. The response of these
      promoters in reporter assays to transfected C/EBPalpha and C/EBPbeta proteins was
      consistent with the promoter binding assays and emphasized the relative
      importance of C/EBPs for activation of the ZTA promoter. Mutation of the oriLyt
      promoter proximal C/EBP site had little effect on ZTA activation of the promoter
      in a reporter assay. However, this mutation impaired oriLyt DNA replication,
      suggesting a separate replication-specific contribution for C/EBP proteins.
      Finally, the overall importance of C/EBP proteins for lytic gene expression was
      demonstrated using CHOP10 to antagonize C/EBP DNA binding activity. Introduction
      of CHOP10 significantly impaired induction of the ZTA, RTA, and BMRF1 proteins in
      chemically treated AGS/BX1 cells. Thus, C/EBPbeta and C/EBPalpha expression are
      associated with lytic induction in AGS cells, and expression of C/EBP proteins in
      epithelial cells may contribute to the tendency of these cells to exhibit
      constitutive low-level ZTA promoter activity.

PMID- 16414988
TI  - Activated MEK suppresses activation of PKR and enables efficient replication and
      in vivo oncolysis by Deltagamma(1)34.5 mutants of herpes simplex virus 1.
AB  - Herpes simplex virus mutants lacking the gamma(1)34.5 gene are not destructive to
      normal tissues but are potent cytolytic agents in human tumor cells in which the
      activation of double-stranded RNA-dependent protein kinase (PKR) is suppressed.
      Thus, replication of a Deltagamma(1)34.5 mutant (R3616) in 12 genetically defined
      cancer cell lines correlates with suppression of PKR but not with the genotype of
      RAS. Extensive analyses of two cell lines transduced with either dominant
      negative MEK (dnMEK) or constitutively active MEK (caMEK) indicated that in R3616
      mutant-infected cells dnMEK enabled PKR activation and decreased virus yields,
      whereas caMEK suppressed PKR and enabled better viral replication and cell
      destruction in transduced cells in vitro or in mouse xenografts. The results
      indicate that activated MEK mediates the suppression of PKR and that the status
      of MEK predicts the ability of Deltagamma(1)34.5 mutant viruses to replicate in
      and destroy tumor cells.

PMID- 16414989
TI  - A methionine-rich domain mediates CRM1-dependent nuclear export activity of Borna
      disease virus phosphoprotein.
AB  - Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that
      replicates and transcribes in the nucleus of infected cells. Recently, we have
      demonstrated that BDV phosphoprotein (P) can modulate its subcellular
      localization through binding to the protein X, which is encoded in the
      overlapping open reading frame (T. Kobayashi et al., J. Virol. 77:8099-8107,
      2003). This observation suggested a unique strategy of intracellular trafficking
      of a viral protein that is essential for the formation of a functional BDV
      ribonucleoprotein (RNP). However, neither the mechanism nor the consequences of
      the cytoplasmic retention or nuclear export of BDV X-P complex have been
      elucidated. In this study, we show that BDV P contains a bona fide nuclear export
      signal (NES) and can actively shuttle between the nucleus and cytoplasm. A
      transient transfection analysis of cDNA clones that mimic the BDV bicistronic X/P
      mRNA revealed that the methionine-rich (MetR) domain of P is responsible for the
      X-dependent cytoplasmic localization of the protein complex. Mutational and
      functional analysis revealed that the methionine residues within the MetR domain
      are critical for the activity of the NES of P. Furthermore, leptomycin B or small
      interfering RNA for inhibition of CRM1 strongly suggested that a CRM1-dependent
      pathway mediates nuclear export of P. Fluorescence loss in photobleaching
      analysis confirmed the nucleocytoplasmic shuttling of P. Moreover, we revealed
      that the nuclear export of P is not involved in the inhibition of the polymerase
      activity by X in the BDV minireplicon system. Our results may provide a unique
      strategy for the nucleocytoplasmic transport of viral RNP, which could be
      critical for the formation of not only infectious virions in the cytoplasm but
      also a persistent viral state in the nucleus.

PMID- 16414990
TI  - Protection against respiratory syncytial virus by a recombinant Newcastle disease
      virus vector.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory
      tract disease in infants and the elderly, but no safe and effective RSV vaccine
      is yet available. For reasons that are not well understood, RSV is only weakly
      immunogenic, and reinfection occurs throughout life. This has complicated the
      search for an effective live attenuated viral vaccine, and past trials with
      inactivated virus preparations have led to enhanced immunopathology following
      natural infection. We have tested the hypothesis that weak stimulation of innate
      immunity by RSV correlates with ineffective adaptive responses by asking whether
      expression of the fusion glycoprotein of RSV by Newcastle disease virus (NDV)
      would stimulate a more robust immune response to RSV than primary RSV infection.
      NDV is a potent inducer of both alpha/beta interferon (IFN-alpha/beta) production
      and dendritic cell maturation, while RSV is not. When a recombinant NDV
      expressing the RSV fusion glycoprotein was administered to BALB/c mice, they were
      protected from RSV challenge, and this protection correlated with a robust anti-F
      CD8+ T-cell response. The effectiveness of this vaccine construct reflects the
      differential abilities of NDV and RSV to promote dendritic cell maturation and is
      retained even in the absence of a functional IFN-alpha/beta receptor.

PMID- 16414991
TI  - Myxoma virus M11L blocks apoptosis through inhibition of conformational
      activation of Bax at the mitochondria.
AB  - Many viruses inhibit or retard apoptosis, a strategy that subverts one of the
      most ancient antiviral mechanisms. M11L, a myxoma virus-encoded antiapoptotic
      protein, has been previously shown to localize to mitochondria and block
      apoptosis of virus-infected cells (H. Everett, M. Barry, S. F. Lee, X. J. Sun, K.
      Graham, J. Stone, R. C. Bleackley, and G. McFadden, J. Exp. Med. 191:1487-1498,
      2000; H. Everett, M. Barry, X. Sun, S. F. Lee, C. Frantz, L. G. Berthiaume, G.
      McFadden, and R. C. Bleackley, J. Exp. Med. 196:1127-1139, 2002; and G. Wang, J.
      W. Barrett, S. H. Nazarian, H. Everett, X. Gao, C. Bleackley, K. Colwill, M. F.
      Moran, and G. McFadden, J. Virol. 78:7097-7111, 2004). This protection from
      apoptosis involves constitutive-forming inhibitory complexes with the peripheral
      benzodiazepine receptor and Bak on the outer mitochondrial membrane. Here, we
      extend the study to investigate the interference of M11L with Bax activation
      during the process of apoptosis. Myxoma virus infection triggers an early
      apoptotic signal that induces rapid Bax translocation from cytoplasm to
      mitochondria, despite the existence of various viral antiapoptotic proteins.
      However, in the presence of M11L, the structural activation of Bax at the
      mitochondrial membrane, which is characterized by the occurrence of a Bax
      conformational change, is blocked in both M11L-expressing myxoma-infected cells
      and M11L-transfected cells under apoptotic stimulation. In addition, inducible
      binding of M11L to the mitochondrially localized Bax is detected in myxoma virus
      infected cells and in M11L/Bax-cotransfected cells as measured by
      immunoprecipitation and tandem affinity purification analysis, respectively.
      Importantly, this inducible Bax/M11L interaction is independent of Bak,
      demonstrated by the complete block of Bax-mediated apoptosis in myxoma-infected
      cells that lack Bak expression. Our findings reveal that myxoma M11L modulates
      apoptosis by multiple independent strategies which all contribute to the blockade
      of apoptosis at the mitochondrial checkpoint.

PMID- 16414992
TI  - Transduction of nondividing human macrophages with gammaretrovirus-derived
      vectors.
AB  - It is commonly accepted that infection of nondividing cells by gammaretroviruses
      such as the murine leukemia viruses is inefficient due to their inability to
      cross the nuclear envelope barrier. Challenging this notion, we now show that
      human nondividing macrophages display a specific window of susceptibility to
      transduction with a Friend murine leukemia virus (F-MLV)-derived vector during
      their differentiation from monocytes. This finding suggests that factors other
      than the nuclear membrane govern permissiveness to gammaretroviral infection and
      raises the possibility of using the macrophage tropism of F-MLV in gene therapy.

PMID- 16414993
TI  - Nuclear localization and dynamic properties of the Marek's disease virus oncogene
      products Meq and Meq/vIL8.
AB  - Marek's disease virus (MDV) is an avian herpesvirus that causes T-cell lymphomas
      and immune suppression in susceptible chickens. At least one gene product, MDV
      Eco Q-encoded protein (Meq), is essential for the oncogenicity of MDV.
      Alternative splicing permits the meq gene to give rise to two major transcripts
      encoding proteins designated Meq and Meq/vIL8. Meq is a basic leucine zipper
      protein capable of modulating transcription. The Meq/vIL8 protein retains a
      modified leucine zipper, along with the mature receptor-binding portion of vIL8,
      but lacks the domain of Meq responsible for transcriptional modulation. In this
      report, we describe studies using fusions between either Meq or Meq/vIL8 and
      fluorescent proteins to characterize the distribution and properties of these
      products in chicken embryo fibroblasts (CEFs). Meq and Meq/vIL8 both localized to
      the nucleoplasm, nucleoli, and Cajal bodies of transfected cells. Similar
      distributions were found for fluorescent fusion proteins and native Meq or
      Meq/vIL8. Fluorescence recovery after photobleaching and photoactivatable green
      fluorescent protein revealed that Meq exhibited mobility properties similar to
      those of other transcription factors, while Meq/vIL8 was far less mobile. In
      addition, fluorescence resonance energy transfer studies indicated the formation
      of Meq/vIL8 homodimers in CEFs. Time lapse studies revealed the coordinated
      elimination of a portion of Meq and Meq/vIL8 from the nucleus. Our data provide
      new insight regarding the dynamic cellular properties of two forms of a
      herpesvirus-encoded oncoprotein and suggest that these forms may have
      fundamentally different functions in MDV-infected cells.

PMID- 16414994
TI  - Focal adhesion kinase is critical for entry of Kaposi's sarcoma-associated
      herpesvirus into target cells.
AB  - Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8)
      interacts with cell surface alpha3beta1 integrin early during in vitro infection
      of human endothelial cells and fibroblasts and activates the focal adhesion
      kinase (FAK) that is immediately downstream in the outside-in signaling pathway
      by integrins, leading to the activation of several downstream signaling
      molecules. In this study, using real-time DNA and reverse transcription-PCR
      assays to measure total internalized viral DNA, viral DNA associated with
      infected nuclei, and viral gene expression, we examined the stage of infection at
      which FAK plays the most significant role. Early during KSHV infection, FAK was
      phosphorylated in FAK-positive Du17 mouse embryonic fibroblasts. The absence of
      FAK in Du3 (FAK(-/-)) cells resulted in about 70% reduction in the
      internalization of viral DNA, suggesting that FAK plays a role in KSHV entry.
      Expression of FAK in Du3 (FAK(-/-)) cells via an adenovirus vector augmented the
      internalization of viral DNA. Expression of the FAK dominant-negative mutant FAK
      related nonkinase (FRNK) in Du17 cells significantly reduced the entry of virus.
      Virus entry in Du3 cells, albeit in reduced quantity, delivery of viral DNA to
      the infected cell nuclei, and expression of KSHV genes suggested that in the
      absence of FAK, another molecule(s) may be partially compensating for FAK
      function. Infection of Du3 cells induced the phosphorylation of the FAK-related
      proline-rich tyrosine kinase (Pyk2) molecule, which has been shown to complement
      some of the functions of FAK. Expression of an autophosphorylation site mutant of
      Pyk2 in which Y402 is mutated to F (F402 Pyk2) reduced viral entry in Du3 cells,
      suggesting that Pyk2 facilitates viral entry moderately in the absence of FAK.
      These results suggest a critical role for KSHV infection-induced FAK in the
      internalization of viral DNA into target cells.

PMID- 16414995
TI  - Effect of cell growth on hepatitis C virus (HCV) replication and a mechanism of
      cell confluence-based inhibition of HCV RNA and protein expression.
AB  - An intimate relationship between hepatitis C virus (HCV) replication and the
      physiological state of the host liver cells has been reported. In particular, a
      highly reproducible and reversible inhibitory effect of high cell density on HCV
      replication was observed: high levels of HCV RNA and protein can be detected in
      actively growing cells but decline sharply when the replicon cells reach
      confluence. Arrested cell growth of confluent cells has been proposed to be
      responsible for the inhibitory effect. Indeed, other means of arresting cell
      growth have also been shown to inhibit HCV replication. Here, we report a
      detailed study of the effect of cell growth and confluence on HCV replication
      using a flow cytometry-based assay that is not biased against cytostasis and
      reduced cell number. Although we readily reproduced the inhibitory effect of cell
      confluence on HCV replication, we found no evidence of inhibition by serum
      starvation, which arrested cell growth as expected. In addition, we observed no
      inhibitory effect by agents that perturb the cell cycle. Instead, our results
      suggest that the reduced intracellular pools of nucleosides account for the
      suppression of HCV expression in confluent cells, possibly through the shutoff of
      the de novo nucleoside biosynthetic pathway when cells become confluent. Adding
      exogenous uridine and cytidine to the culture medium restored HCV replication and
      expression in confluent cells. These results suggest that cell growth arrest is
      not sufficient for HCV replicon inhibition and reveal a mechanism for HCV RNA
      inhibition by cell confluence.

PMID- 16414996
TI  - Infection-dependent nuclear localization of US17, a member of the US12 family of
      human cytomegalovirus-encoded seven-transmembrane proteins.
AB  - The human cytomegalovirus (HCMV) US12 gene family is a group of predicted seven
      transmembrane, G-protein-coupled receptor-related proteins, about which little is
      known. Specific rabbit polyclonal antibodies detected US17 and US18 beginning 54
      and 36 h after infection, respectively, with expression of both proteins
      dependent on viral DNA synthesis. While US14 and US18 are expressed exclusively
      in the cytoplasm, we unexpectedly found abundant expression of US17 in both the
      cytoplasm and nucleoplasm. N- and C-terminally tagged versions of US17 were
      readily detected in the cytoplasm of transfected mammalian cells, but not in
      nuclei, suggesting that nuclear localization involves other viral proteins or an
      infection-triggered cellular process. There was no specific colocalization
      between US17 and other nuclear expressed HCMV-encoded proteins (IE-2, DNA
      polymerase processivity factor, and pp28/UL99). To determine whether the observed
      nuclear localization might be the product of a process by which a soluble C
      terminal segment of the full-length protein is expressed, we constructed a
      recombinant virus that incorporates a synthetic epitope at its N terminus, which
      in conjunction with the antipeptide antibody that targets its predicted
      cytoplasmic C-terminal segment, enables simultaneous independent detection of
      both termini. In cells infected with the recombinant, the US17 N and C termini
      had limited colocalization, with the N-terminal segment not detected in nuclei,
      supporting the segmentation hypothesis. Consistent with this, a fragment with an
      apparent molecular size of 10 kDa was detected by immunoblotting. We have
      identified the first viral example of a seven-transmembrane protein that is
      either segmented or expressed in nuclei. Further study will be required to learn
      the mechanism by which this occurs and the function of the nuclear localizing
      segment. This likely represents yet another mechanism by which a virus has
      hijacked or modified cellular regulatory pathways for its benefit.

PMID- 16414997
TI  - Paramyxovirus receptor-binding molecules: engagement of one site on the
      hemagglutinin-neuraminidase protein modulates activity at the second site.
AB  - The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses carries out three
      different activities: receptor binding, receptor cleaving (neuraminidase), and
      triggering of the fusion protein. These three discrete properties each affect the
      ability of HN to promote viral fusion and entry. For human parainfluenza type 3,
      one bifunctional site on HN can carry out both binding and neuraminidase, and the
      receptor mimic, zanamivir, impairs viral entry by blocking receptor binding. We
      report here that for Newcastle disease virus, the HN receptor avidity is
      increased by zanamivir, due to activation of a second site that has higher
      receptor avidity. Only certain receptor mimics effectively activate the second
      site (site II) via occupation of site I; yet without activation of this second
      site, binding is mediated entirely by site I. Computational modeling designed to
      complement the experimental approaches suggests that the potential for small
      molecule receptor mimics to activate site II, upon binding to site I, directly
      correlates with their predicted strengths of interaction with site I. Taken
      together, the experimental and computational data show that the molecules with
      the strongest interactions with site I-zanamivir and BCX 2798-lead to the
      activation of site II. The finding that site II, once activated, shows higher
      avidity for receptor than site I, suggests paradigms for further elucidating the
      regulation of HN's multiple functions in the viral life cycle.

PMID- 16414998
TI  - The complete genome sequence of herpesvirus papio 2 (Cercopithecine herpesvirus
      16) shows evidence of recombination events among various progenitor
      herpesviruses.
AB  - We have sequenced the entire genome of herpesvirus papio 2 (HVP-2; Cercopithecine
      herpesvirus 16) strain X313, a baboon herpesvirus with close homology to other
      primate alphaherpesviruses, such as SA8, monkey B virus, and herpes simplex virus
      (HSV) type 1 and type 2. The genome of HVP-2 is 156,487 bp in length, with an
      overall GC content of 76.5%. The genome organization is identical to that of the
      other members of the genus Simplexvirus, with a long and a short unique region,
      each bordered by inverted repeats which end with an "a" sequence. All of the open
      reading frames detected in this genome were homologous and colinear with those of
      SA8 and B virus. The HSV gene RL1 (gamma(1)34.5; neurovirulence factor) is not
      present in HVP-2, as is the case for SA8 and B virus. The HVP-2 genome is 85%
      homologous to its closest relative, SA8. However, segment-by-segment bootstrap
      analysis of the genome revealed at least two regions that display closer homology
      to the corresponding sequences of B virus. The first region comprises the UL41 to
      UL44 genes, and the second region is located within the UL36 gene. We hypothesize
      that this localized and defined shift in homology is due to recombination events
      between an SA8-like progenitor of HVP-2 and a herpesvirus species more closely
      related to the B virus. Since some of the genes involved in these putative
      recombination events are determinants of virulence, a comparative analysis of
      their function may provide insight into the pathogenic mechanism of
      simplexviruses.

PMID- 16414999
TI  - Perforin-deficient CD8+ T cells mediate fatal lymphocytic choriomeningitis
      despite impaired cytokine production.
AB  - Intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) is
      one of the most studied models for virus-induced immunopathology, and based on
      results from perforin-deficient mice, it is currently assumed that fatal disease
      directly reflects perforin-mediated cell lysis. However, recent studies have
      revealed additional functional defects within the effector T cells of LCMV
      infected perforin-deficient mice, raising the possibility that perforin may not
      be directly involved in mediating lethal disease. For this reason, we decided to
      reevaluate the role of perforin in determining the outcome of i.c. infection with
      LCMV. We confirmed that the expansion of virus-specific CD8(+) T cells is
      unimpaired in perforin-deficient mice. However, despite the fact that the virus
      specific CD8(+) effector T cells in perforin-deficient mice are broadly impaired
      in their effector function, these mice invariably succumb to i.c. infection with
      LCMV strain Armstrong, although a few days later than matched wild-type mice.
      Upon further investigation, we found that this delay correlates with the delayed
      recruitment of inflammatory cells to the central nervous system (CNS). However,
      CD8(+) effector T cells were not kept from the CNS by sequestering in infected
      extraneural organ sites such as liver or lungs. Thus, the observed
      dysfunctionality regarding the production of proinflammatory mediators probably
      results in the delayed recruitment of effector cells to the CNS, and this appears
      to be the main explanation for the delayed onset of fatal disease in perforin
      deficient mice. However, once accumulated in the CNS, virus-specific CD8(+) T
      cells can induce fatal CNS pathology despite the absence of perforin-mediated
      lysis and reduced capacity to produce several key cytokines.

PMID- 16415000
TI  - Screening of the yeast yTHC collection identifies essential host factors
      affecting tombusvirus RNA recombination.
AB  - RNA recombination is a major process in promoting rapid virus evolution in an
      infected host. A previous genome-wide screen with the yeast single-gene deletion
      library of 4,848 strains, representing approximately 80% of all genes of yeast,
      led to the identification of 11 host genes affecting RNA recombination in Tomato
      bushy stunt virus (TBSV), a small model plant virus (E. Serviene, N. Shapka, C.
      P. Cheng, T. Panavas, B. Phuangrat, J. Baker, and P. D. Nagy, Proc. Natl. Acad.
      Sci. USA 102:10545-10550, 2005). To further test the role of host genes in viral
      RNA recombination, in this paper, we extended the screening to 800 essential
      yeast genes present in the yeast Tet-promoters Hughes Collection (yTHC). In
      total, we identified 16 new host genes that either increased or decreased the
      ratio of TBSV recombinants to the nonrecombined TBSV RNA. The identified
      essential yeast genes are involved in RNA transcription/metabolism, in protein
      metabolism/transport, or unknown cellular processes. Detailed analysis of the
      effect of the identified yeast genes revealed that they might affect RNA
      recombination by altering (i) the ratio of the two viral replication proteins,
      (ii) the stability of the viral RNA, and/or (iii) the replicability of the
      recombinant RNAs. Overall, this and previous works firmly establish that a set of
      essential and nonessential host genes could affect TBSV recombination and
      evolution.

PMID- 16415001
TI  - Effects of Gag mutation and processing on retroviral dimeric RNA maturation.
AB  - After their release from host cells, most retroviral particles undergo a
      maturation process, which includes viral protein cleavage, core condensation, and
      increased stability of the viral RNA dimer. Inactivating the viral protease
      prevents protein cleavage; the resulting virions lack condensed cores and contain
      fragile RNA dimers. Therefore, protein cleavage is linked to virion morphological
      change and increased stability of the RNA dimer. However, it is unclear whether
      protein cleavage is sufficient for mediating virus RNA maturation. We have
      observed a novel phenotype in a murine leukemia virus capsid mutant, which has
      normal virion production, viral protein cleavage, and RNA packaging. However,
      this mutant also has immature virion morphology and contains a fragile RNA dimer,
      which is reminiscent of protease-deficient mutants. To our knowledge, this mutant
      provides the first evidence that Gag cleavage alone is not sufficient to promote
      RNA dimer maturation. To extend our study further, we examined a well-defined
      human immunodeficiency virus type 1 (HIV-1) Gag mutant that lacks a functional
      PTAP motif and produces immature virions without major defects in viral protein
      cleavage. We found that the viral RNA dimer in the PTAP mutant is more fragile
      and unstable compared with those from wild-type HIV-1. Based on the results of
      experiments using two different Gag mutants from two distinct retroviruses, we
      conclude that Gag cleavage is not sufficient for promoting RNA dimer maturation,
      and we propose that there is a link between the maturation of virion morphology
      and the viral RNA dimer.

PMID- 16415002
TI  - Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting
      adapter.
AB  - Murine hepatitis coronavirus (MHV)-A59 infection depends on the interaction of
      its spike (S) protein with the cellular receptor mCEACAM1a present on murine
      cells. Human cells lack this receptor and are therefore not susceptible to MHV.
      Specific alleviation of the tropism barrier by redirecting MHV to a tumor
      specific receptor could lead to a virus with appealing properties for tumor
      therapy. To demonstrate that MHV can be retargeted to a nonnative receptor on
      human cells, we produced bispecific adapter proteins composed of the N-terminal
      D1 domain of mCEACAM1a linked to a short targeting peptide, the six-amino-acid
      His tag. Preincubation of MHV with the adapter proteins and subsequent
      inoculation of human cells expressing an artificial His receptor resulted in
      infection of these otherwise nonsusceptible cells and led to subsequent
      production of progeny virus. To generate a self-targeted virus able to establish
      multiround infection of the target cells, we subsequently incorporated the gene
      encoding the bispecific adapter protein as an additional expression cassette into
      the MHV genome through targeted RNA recombination. When inoculated onto murine
      LR7 cells, the resulting recombinant virus indeed expressed the adapter protein.
      Furthermore, inoculation of human target cells with the virus resulted in a His
      receptor-specific infection that was multiround. Extensive cell-cell fusion and
      rapid cell killing of infected target cells was observed. Our results show that
      MHV can be genetically redirected via adapters composed of the S protein binding
      part of mCEACAM1a and a targeting peptide recognizing a nonnative receptor
      expressed on human cells, consequently leading to rapid cell death. The results
      provide interesting leads for further investigations of the use of coronaviruses
      as antitumor agents.

PMID- 16415004
TI  - Functional analyses of RNA structures shared between the internal ribosome entry
      sites of hepatitis C virus and the picornavirus porcine teschovirus 1 Talfan.
AB  - The internal ribosome entry site (IRES) of porcine teschovirus 1 (PTV-1), a
      member of the Picornaviridae family, is quite distinct from other well
      characterized picornavirus IRES elements, but it displays functional similarities
      to the IRES from hepatitis C virus (HCV), a member of the Flaviviridae family. In
      particular, a dominant negative mutant form of eIF4A does not inhibit the
      activity of the PTV-1 IRES. Furthermore, there is a high level (ca. 50%) of
      identity between the PTV-1 and HCV IRES sequences. A secondary-structure model of
      the whole PTV-1 IRES has been derived which includes a pseudoknot. Validation of
      specific features within the model has been achieved by mutagenesis and
      functional assays. The differences and similarities between the PTV-1 and HCV
      IRES elements should assist in defining the critical features of this type of
      IRES.

PMID- 16415003
TI  - JAM-A-independent, antibody-mediated uptake of reovirus into cells leads to
      apoptosis.
AB  - Apoptosis plays a major role in the cytopathic effect induced by reovirus
      following infection of cultured cells and newborn mice. Strain-specific
      differences in the capacity of reovirus to induce apoptosis segregate with the S1
      and M2 gene segments, which encode attachment protein sigma1 and membrane
      penetration protein mu1, respectively. Virus strains that bind to both junctional
      adhesion molecule-A (JAM-A) and sialic acid are the most potent inducers of
      apoptosis. In addition to receptor binding, events in reovirus replication that
      occur during or after viral disassembly but prior to initiation of viral RNA
      synthesis also are required for reovirus-induced apoptosis. To determine whether
      reovirus infection initiated in the absence of JAM-A and sialic acid results in
      apoptosis, Chinese hamster ovary (CHO) cells engineered to express Fc receptors
      were infected with reovirus using antibodies directed against viral outer-capsid
      proteins. Fc-mediated infection of CHO cells induced apoptosis in a sigma1
      independent manner. Apoptosis following this uptake mechanism requires acid
      dependent proteolytic disassembly, since treatment of cells with the weak base
      ammonium chloride diminished the apoptotic response. Analysis of T1L x T3D
      reassortant viruses revealed that the mu1-encoding M2 gene segment is the only
      viral determinant of the apoptosis-inducing capacity of reovirus when infection
      is initiated via Fc receptors. Additionally, a temperature-sensitive, membrane
      penetration-defective M2 mutant, tsA279.64, is an inefficient inducer of
      apoptosis. These data suggest that signaling pathways activated by binding of
      sigma1 to JAM-A and sialic acid are dispensable for reovirus-mediated apoptosis
      and that the mu1 protein plays an essential role in stimulating proapoptotic
      signaling.

PMID- 16415005
TI  - Palmitoylations on murine coronavirus spike proteins are essential for virion
      assembly and infectivity.
AB  - Coronavirus spike (S) proteins are palmitoylated at several cysteine residues
      clustered near their transmembrane-spanning domains. This is achieved by cellular
      palmitoyl acyltransferases (PATs), which can modify newly synthesized S proteins
      before they are assembled into virion envelopes at the intermediate compartment
      of the exocytic pathway. To address the importance of these fatty acylations to
      coronavirus infection, we exposed infected cells to 2-bromopalmitate (2-BP), a
      specific PAT inhibitor. 2-BP profoundly reduced the specific infectivities of
      murine coronaviruses at very low, nontoxic doses that were inert to alphavirus
      and rhabdovirus infections. 2-BP effected only two- to fivefold reductions in S
      palmitoylation, yet this correlated with reduced S complexing with virion
      membrane (M) proteins and consequent exclusion of S from virions. At defined 2-BP
      doses, underpalmitoylated S proteins instead trafficked to infected cell surfaces
      and elicited cell-cell membrane fusions, suggesting that the acyl chain adducts
      are more critical to virion assembly than to S-induced syncytial developments.
      These studies involving pharmacologic inhibition of S protein palmitoylation were
      complemented with molecular genetic analyses in which cysteine acylation
      substrates were mutated. Notably, some mutations (C1347F and C1348S) did not
      interfere with S incorporation into virions, indicating that only a subset of the
      cysteine-rich region provides the essential S-assembly functions. However, the
      C1347F/C1348S mutant viruses exhibited relatively low specific infectivities,
      similar to virions secreted from 2-BP-treated cultures. Our collective results
      indicate that the palmitate adducts on coronavirus S proteins are necessary in
      assembly and also in positioning the assembled envelope proteins for maximal
      infectivity.

PMID- 16415007
TI  - Important role for the transmembrane domain of severe acute respiratory syndrome
      coronavirus spike protein during entry.
AB  - The spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV)
      is responsible for receptor binding and membrane fusion. It contains a highly
      conserved transmembrane domain that consists of three parts: an N-terminal
      tryptophan-rich domain, a central domain, and a cysteine-rich C-terminal domain.
      The cytoplasmic tail of S has previously been shown to be required for assembly.
      Here, the roles of the transmembrane and cytoplasmic domains of S in the
      infectivity and membrane fusion activity of SARS-CoV have been studied. SARS-CoV
      S-pseudotyped retrovirus (SARSpp) was used to measure S-mediated infectivity. In
      addition, the cell-cell fusion activity of S was monitored by a Renilla
      luciferase-based cell-cell fusion assay. S(VSV-Cyt), an S chimera with a
      cytoplasmic tail derived from vesicular stomatitis virus G protein (VSV-G), and
      S(MHV-TMDCyt), an S chimera with the cytoplasmic and transmembrane domains of
      mouse hepatitis virus, displayed wild-type-like activity in both assays. S(VSV
      TMDCyt), a chimera with the cytoplasmic and transmembrane domains of VSV-G, was
      impaired in the SARSpp and cell-cell fusion assays, showing 3 to 25% activity
      compared to the wild type, depending on the assay and the cells used. Examination
      of the oligomeric state of the chimeric S proteins in SARSpp revealed that S(VSV
      TMDCyt) trimers were less stable than wild-type S trimers, possibly explaining
      the lowered fusogenicity and infectivity.

PMID- 16415006
TI  - West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular
      attachment and infection.
AB  - The C-type lectins DC-SIGN and DC-SIGNR bind mannose-rich glycans with high
      affinity. In vitro, cells expressing these attachment factors efficiently
      capture, and are infected by, a diverse array of appropriately glycosylated
      pathogens, including dengue virus. In this study, we investigated whether these
      lectins could enhance cellular infection by West Nile virus (WNV), a mosquito
      borne flavivirus related to dengue virus. We discovered that DC-SIGNR promoted
      WNV infection much more efficiently than did DC-SIGN, particularly when the virus
      was grown in human cell types. The presence of a single N-linked glycosylation
      site on either the prM or E glycoprotein of WNV was sufficient to allow DC-SIGNR
      mediated infection, demonstrating that uncleaved prM protein present on a
      flavivirus virion can influence viral tropism under certain circumstances.
      Preferential utilization of DC-SIGNR was a specific property conferred by the WNV
      envelope glycoproteins. Chimeras between DC-SIGN and DC-SIGNR demonstrated that
      the ability of DC-SIGNR to promote WNV infection maps to its carbohydrate
      recognition domain. WNV virions and subviral particles bound to DC-SIGNR with
      much greater affinity than DC-SIGN. We believe this is the first report of a
      pathogen interacting more efficiently with DC-SIGNR than with DC-SIGN. Our
      results should lead to the discovery of new mechanisms by which these well
      studied lectins discriminate among ligands.

PMID- 16415008
TI  - Dynamic evolution of the human immunodeficiency virus type 1 pathogenic factor,
      Nef.
AB  - The human immunodeficiency virus type 1 (HIV-1) early gene product Nef is a
      multifunctional protein that alters numerous pathways of T-cell function,
      including endocytosis, signal transduction, vesicular trafficking, and immune
      modulation, and is a major determinant of pathogenesis. Individual Nef functions
      include PAK-2 activation, CD4 downregulation, major histocompatibility complex
      (MHC) class I downregulation, and enhancement of viral particle infectivity. How
      Nef accomplishes its multiple tasks presents a difficult problem of mechanistic
      analysis because of the complications associated with multiple, overlapping
      functional domains in the context of significant sequence variability. To address
      these issues we determined the conservation of each Nef residue based on 1,643
      subtype B Nef sequences. Mutational analysis based on conservative substitutions
      and Nef sequence data allowed us to search for amino acids on the surface of Nef
      that are specifically required for PAK-2 activation. We found residues 85, 89,
      and 191 to be highly significant determinants for Nef's PAK-2 activation function
      but functionally unlinked to CD4 and MHC class I downregulation or enhancement of
      infectivity. These residues are not conserved across HIV-1 subtypes but are
      confined to separate sets of surface elements within a subtype. Thus,
      L85/H89/F191 and F85/F89/R191 are dominant in subtype B and subtype E or C,
      respectively. Our results provide support for developing subtype-specific
      interventions in HIV-1 disease.

PMID- 16415010
TI  - Composition of pseudorabies virus particles lacking tegument protein US3, UL47,
      or UL49 or envelope glycoprotein E.
AB  - Proteins located in the tegument layer of herpesvirus particles play important
      roles in the replicative cycle at both early and late times after infection. As
      major constituents of the virion, they execute important functions in particular
      during formation of progeny virions. These functions have mostly been elucidated
      by construction and analysis of mutant viruses deleted in single or multiple
      tegument protein-encoding genes (reviewed in the work of T. C. Mettenleiter,
      Virus Res. 106:167-180, 2004). However, since tegument proteins have been shown
      to be involved in numerous protein-protein interactions, the impact of single
      protein deletions on the composition of the virus particle is unknown, but they
      could impair correct interpretation of the results. To analyze how the absence of
      single virion constituents influences virion composition, we established a
      procedure to assay relative amounts of virion structural proteins in deletion
      mutants of the alphaherpesvirus Pseudorabies virus (PrV) in comparison to wild
      type particles. The assay is based on the mass spectrometric quantitation of
      virion protein-derived peptides carrying stable isotope mass tags. After deletion
      of the US3, UL47, UL49, or glycoprotein E gene, relative amounts of a capsid
      protein (UL38), a capsid-associated protein (UL25), several tegument proteins
      (UL36 and UL47, if present), and glycoprotein H were unaffected, whereas the
      content of other tegument proteins (UL46, UL48, and UL49, if present) varied
      significantly. In the case of the UL48 gene product, a specific increase in
      incorporation of a smaller isoform was observed after deletion of the UL47 or
      UL49 gene, whereas a larger isoform remained unaffected. The cellular protein
      actin was enriched in virions of mutants deficient in any of the tegument
      proteins UL47, UL49, or US3. By two-dimensional gel electrophoresis multiple
      isoforms of host cell-derived heat shock protein 70 and annexins A1 and A2 were
      also identified as structural components of PrV virions.

PMID- 16415009
TI  - Epstein-Barr virus protein can upregulate cyclo-oxygenase-2 expression through
      association with the suppressor of metastasis Nm23-H1.
AB  - Previous studies have demonstrated the interaction between the Epstein-Barr virus
      (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in
      vitro and in vivo (C. Subramanian, M. A. Cotter II, and E. S. Robertson, Nat.
      Med. 7:350-355, 2001). EBNA3C can reverse the ability of Nm23-H1 to suppress
      migration of Burkitt's lymphoma and breast carcinoma cell lines in vitro. EBNA3C
      contributes to EBV-associated human cancers by regulating transcription of a
      number of cellular and viral promoters and by targeting and altering the
      transcription activities of the metastasis suppressor Nm23-H1. Cyclo-oxygenase-2
      (COX-2), an inducible enzyme important in inflammation, is overexpressed in a
      variety of cancers and can influence cell migration. In this report we show that
      Nm23-H1 and EBNA3C can modulate expression of COX-2 in the context of EBV
      infection and transformation. The levels of COX-2 were consistently higher in EBV
      positive cells than in EBV-negative cells. Additionally, we show that Nm23-H1 can
      upregulate the COX-2 promoter element in luciferase reporter assays, whereas
      EBNA3C alone did not affect the level of response but clearly contributed to an
      additive increase when coexpressed with Nm23-H1. The downstream effect of COX-2
      expression was also evaluated and showed that prostaglandin E(2) levels increased
      with Nm23-H1 and that there was some level of cooperativity in the presence of
      EBNA3C. The majority of this response was mediated through the cyclic AMP
      response element and NF-kappaB sites. These studies suggest a potential role for
      COX-2 in EBV-associated human cancers.

PMID- 16415012
TI  - Stable growth of wild-type hepatitis A virus in cell culture.
AB  - Human wild-type (wt) hepatitis A virus (HAV), the causative agent of acute
      hepatitis, barely grows in cell culture and in the process accumulates
      attenuating and cell culture-adapting mutations. This genetic instability of wt
      HAV in cell culture is a major roadblock to studying HAV pathogenesis and
      producing live vaccines that are not overly attenuated for humans. To develop a
      robust cell culture system capable of supporting the efficient growth of wt HAV,
      we transfected different cell lines with in vitro RNA transcripts of wt HAV
      containing the blasticidin resistance gene. Blasticidin-resistant colonies grew
      only in transfected Huh7 cells and produced infectious virus. HAV was genetically
      stable in Huh7 cells for at least nine serial passages and did not accumulate
      attenuating or cell culture-adapting mutations. Treatment with alpha interferon
      A/D cured the blasticidin-resistant Huh7 cells of the HAV infection. The cured
      cells, termed Huh7-A-I cells, did not contain virus or HAV antigens and were
      sensitive to blasticidin. Huh7-A-I cells were more permissive than parental cells
      for wt HAV infection, including a natural isolate from a human stool sample, and
      produced 10-fold-more infectious particles. This is the first report of a cell
      line that allows the genetically stable growth of human wt HAV. The viral vectors
      and cells described here should allow better insight into the pathogenesis of HAV
      and the development of attenuated vaccines. The cell lines susceptible to wt HAV
      growth may also be used to detect and isolate infectious virus from patient and
      environmental samples.

PMID- 16415011
TI  - Antibodies against West Nile Virus nonstructural protein NS1 prevent lethal
      infection through Fc gamma receptor-dependent and -independent mechanisms.
AB  - The flavivirus nonstructural protein NS1 is a highly conserved secreted
      glycoprotein that does not package with the virion. Immunization with NS1 elicits
      a protective immune response against yellow fever, dengue, and tick-borne
      encephalitis flaviviruses through poorly defined mechanisms. In this study, we
      purified a recombinant, secreted form of West Nile virus (WNV) NS1 glycoprotein
      from baculovirus-infected insect cells and generated 22 new NS1-specific
      monoclonal antibodies (MAbs). By performing competitive binding assays and
      expressing truncated NS1 proteins on the surface of yeast (Saccharomyces
      cerevisiae) and in bacteria, we mapped 21 of the newly generated MAbs to three
      NS1 fragments. Prophylaxis of C57BL/6 mice with any of four MAbs (10NS1, 14NS1,
      16NS1, and 17NS1) strongly protected against lethal WNV infection (75 to 95%
      survival, respectively) compared to saline-treated controls (17% survival). In
      contrast, other anti-NS1 MAbs of the same isotype provided no significant
      protection. Notably, 14NS1 and 16NS1 also demonstrated marked efficacy as
      postexposure therapy, even when administered as a single dose 4 days after
      infection. Virologic analysis showed that 17NS1 protects at an early stage in
      infection through a C1q-independent and Fc gamma receptor-dependent pathway.
      Interestingly, 14NS1, which maps to a distinct region on NS1, protected through a
      C1q- and Fc gamma receptor-independent mechanism. Overall, our data suggest that
      distinct regions of NS1 can elicit protective humoral immunity against WNV
      through different mechanisms.

PMID- 16415013
TI  - Identification of gangliosides GD1b and GT1b as receptors for BK virus.
AB  - Gangliosides have been shown to be plasma membrane receptors for both murine
      polyomavirus and SV40, while JC virus uses serotonin receptors. In contrast,
      little is known of the membrane receptor and entry pathway for BK virus (BKV),
      which can cause severe disease in immunosuppressed bone marrow and renal
      transplant patients. Using sucrose flotation assays, we investigated BKV binding
      to and interaction with human erythrocyte membranes and determined that this
      interaction was dependent on a neuraminidase-sensitive, proteinase K-resistant
      molecule. BKV was found to interact with the gangliosides GT1b and GD1b. The
      terminal alpha2-8-linked disialic acid motif, present in both of these
      gangliosides, is likely to be important for this interaction. We also determined
      that the addition of GD1b and GT1b to LNCaP cells, which are normally resistant
      to BKV infection, made them susceptible to the virus. In addition, BKV interacted
      with membranes extracted from the endoplasmic reticulum (ER) and infection was
      blocked by the addition of brefeldin A, which interferes with transport from the
      ER to the Golgi apparatus. These data demonstrate that BKV uses the gangliosides
      GT1b and GD1b as receptors and passes through the ER on the way to the nucleus.

PMID- 16415014
TI  - Divergent patterns of recent retroviral integrations in the human and chimpanzee
      genomes: probable transmissions between other primates and chimpanzees.
AB  - The human genome is littered by endogenous retrovirus sequences (HERVs), which
      constitute up to 8% of the total genomic sequence. The sequencing of the human
      (Homo sapiens) and chimpanzee (Pan troglodytes) genomes has facilitated the
      evolutionary study of ERVs and related sequences. We screened both the human
      genome (version hg16) and the chimpanzee genome (version PanTro1) for ERVs and
      conducted a phylogenetic analysis of recent integrations. We found a number of
      recent integrations within both genomes. They segregated into four groups. Two
      larger gammaretrovirus-like groups (PtG1 and PtG2) occurred in chimpanzees but
      not in humans. The PtG sequences were most similar to two baboon ERVs and a
      macaque sequence but neither to other chimpanzee ERVs nor to any human
      gammaretrovirus-like ERVs. The pattern was consistent with cross-species transfer
      via predation. This appears to be an example of horizontal transfer of
      retroviruses with occasional fixation in the germ line.

PMID- 16415015
TI  - Adenovirus virus-associated RNA is processed to functional interfering RNAs
      involved in virus production.
AB  - Posttranscriptional gene silencing allows sequence-specific control of gene
      expression. Specificity is guaranteed by small antisense RNAs such as microRNAs
      (miRNAs) or small interfering RNAs (siRNAs). Functional miRNAs derive from longer
      double-stranded RNA (dsRNA) molecules that are cleaved to pre-miRNAs in the
      nucleus and are transported by exportin 5 (Exp 5) to the cytoplasm. Adenovirus
      infected cells express virus-associated (VA) RNAs, which are dsRNA molecules
      similar in structure to pre-miRNAs. VA RNAs are also transported by Exp 5 to the
      cytoplasm, where they accumulate. Here we show that small RNAs derived from VA
      RNAs (svaRNAs), similar to miRNAs, can be found in adenovirus-infected cells. VA
      RNA processing to svaRNAs requires neither viral replication nor viral protein
      expression, as evidenced by the fact that svaRNA accumulation can be detected in
      cells transfected with VA sequences. svaRNAs are efficiently bound by Argonaute
      2, the endonuclease of the RNA-induced silencing complex, and behave as
      functional siRNAs, in that they inhibit the expression of reporter genes with
      complementary sequences. Blocking svaRNA-mediated inhibition affects efficient
      adenovirus production, indicating that svaRNAs are required for virus viability.
      Thus, svaRNA-mediated silencing could represent a novel mechanism used by
      adenoviruses to control cellular or viral gene expression.

PMID- 16415016
TI  - Transcriptional regulation of the Kaposi's sarcoma-associated herpesvirus K15
      gene.
AB  - The K15 gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) is a
      transmembrane protein that is encoded by the last open reading frame of the KSHV
      genome. The K15 protein has been implicated in modulation of B-cell signal
      transduction and activation of the Ras/mitogen-activated protein kinase and NF
      kappaB signal transduction pathways. Here we report the identification of the
      transcriptional start site of the full-length K15 gene in KSHV-positive BCBL-1
      cells. We have mapped the K15 transcriptional start site to a position 152
      nucleotides upstream from the translation start site by rapid amplification of
      cDNA ends and RNase protection assays. We have also characterized the K15
      promoter element. To analyze the cis-acting elements necessary to regulate K15
      gene expression, a series of 5' promoter deletion constructs were generated and
      subcloned upstream of the luciferase reporter gene. Transcriptional assays with
      these mutant promoters demonstrated that chemical induction in latently infected
      KSHV-positive BCBL-1 cells activated K15 transcription. In addition, K15 promoter
      transactivation was also mediated by the viral immediate-early protein Orf50/Rta,
      suggesting that the K15 gene is actively transcribed during lytic replication.

PMID- 16415017
TI  - Nuclear export of African swine fever virus p37 protein occurs through two
      distinct pathways and is mediated by three independent signals.
AB  - Nucleocytoplasmic shuttling activity of the African swine fever virus p37
      protein, a major structural protein of this highly complex virus, has been
      recently reported. The systematic characterization of the nuclear export ability
      of this protein constituted the major purpose of the present study. We report
      that both the N- and C-terminal regions of p37 protein are actively exported from
      the nucleus to the cytoplasm of yeast and mammalian cells. Moreover, experiments
      using leptomycin B and small interfering RNAs targeting the CRM1 receptor have
      demonstrated that the export of p37 protein is mediated by both the CRM1
      dependent and CRM1-independent nuclear export pathways. Two signals responsible
      for the CRM1-mediated nuclear export of p37 protein were identified at the N
      terminus of the protein, and an additional signal was identified at the C
      terminal region, which mediates the CRM1-independent nuclear export.
      Interestingly, site-directed mutagenesis revealed that hydrophobic amino acids
      are critical to the function of these three nuclear export signals. Overall, our
      results demonstrate that two distinct pathways contribute to the strong nuclear
      export of full-length p37 protein, which is mediated by three independent nuclear
      export signals. The existence of overlapping nuclear export mechanisms, together
      with our observation that p37 protein is localized in the nucleus at early stages
      of infection and exclusively in the cytoplasm at later stages, suggests that the
      nuclear transport ability of this protein may be critical to the African swine
      fever virus replication cycle.

PMID- 16415018
TI  - Altered proteolysis and global gene expression in hepatitis B virus X transgenic
      mouse liver.
AB  - Hepatitis B virus X (HBX) is essential for the productive infection of hepatitis
      B virus (HBV) in vivo and has a pleiotropic effect on host cells. We have
      previously demonstrated that the proteasome complex is a cellular target of HBX,
      that HBX alters the proteolytic activity of proteasome in vitro, and that
      inhibition of proteasome leads to enhanced viral replication, suggesting that HBX
      and proteasome interaction plays a crucial role in the life cycle and
      pathogenesis of HBV. In the present study, we tested the effect of HBX on the
      proteasome activities in vivo in a transgenic mouse model in which HBX expression
      is developmentally regulated by the mouse major urinary promoter in the liver. In
      addition, microarray analysis was performed to examine the effect of HBX
      expression on the global gene expression profile of the liver. The results showed
      that the peptidase activities of the proteasome were reduced in the HBX
      transgenic mouse liver, whereas the activity of another cellular protease was
      elevated, suggesting a compensatory mechanism in protein degradation. In the
      microarray analysis, diverse genes were altered in the HBX mouse livers and the
      number of genes with significant changes increased progressively with age.
      Functional clustering showed that a number of genes involved in transcription and
      cell growth were significantly affected in the HBX mice, possibly accounting for
      the observed pleiotropic effect of HBX. In particular, insulin-like growth factor
      binding protein 1 was down-regulated in the HBX mouse liver. The down-regulation
      was similarly observed during acute woodchuck hepatitis virus infection. Other
      changes including up-regulation of proteolysis-related genes may also contribute
      to the profound alterations of liver functions in HBV infection.

PMID- 16415019
TI  - Characterization of antibody responses elicited by human immunodeficiency virus
      type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected
      adjuvants.
AB  - We previously reported that soluble, stable YU2 gp140 trimeric human
      immunodeficiency virus type 1 (HIV-1) envelope glycoprotein immunogens could
      elicit improved breadth of neutralization against HIV-1 isolates compared to
      monomeric YU2 gp120 proteins. In this guinea pig immunization study, we sought to
      extend these data and determine if adjuvant could quantitatively or qualitatively
      alter the neutralizing response elicited by trimeric or monomeric immunogens.
      Consistent with our earlier studies, the YU2 gp140 immunogens elicited higher
      titer neutralizing antibodies against homologous and heterologous isolates than
      those elicited by monomeric YU2 gp120. Additionally, the GlaxoSmithKline family
      of adjuvants AS01B, AS02A, and AS03 induced higher levels of neutralizing
      antibodies compared to emulsification of the same immunogens in Ribi adjuvant.
      Further analysis of vaccine sera indicated that homologous virus neutralization
      was not mediated by antibodies to the V3 loop, although V3 loop-directed
      neutralization could be detected for some heterologous isolates. In most gp120
      inoculated animals, the homologous YU2 neutralization activity was inhibited by a
      peptide derived from the YU2 V1 loop, whereas the neutralizing activity elicited
      by YU2 gp140 trimers was much less sensitive to V1 peptide inhibition. Consistent
      with a less V1-focused antibody response, sera from the gp140-immunized animals
      more efficiently neutralized heterologous HIV-1 isolates, as determined by two
      distinct neutralization formats. Thus, there appear to be qualitative differences
      in the neutralizing antibody response elicited by YU2 gp140 compared to YU2
      monomeric gp120. Further mapping analysis of more conserved regions of gp120/gp41
      may be required to determine the neutralizing specificity elicited by the
      trimeric immunogens.

PMID- 16415020
TI  - A tick-borne Langat virus mutant that is temperature sensitive and host range
      restricted in neuroblastoma cells and lacks neuroinvasiveness for immunodeficient
      mice.
AB  - Langat virus (LGT), the naturally attenuated member of the tick-borne
      encephalitis virus (TBEV) complex, was tested extensively in clinical trials as a
      live TBEV vaccine and was found to induce a protective, durable immune response;
      however, it retained a low residual neuroinvasiveness in mice and humans. In
      order to ablate or reduce this property, LGT mutants that produced a small plaque
      size or temperature-sensitive (ts) phenotype in Vero cells were generated using 5
      fluorouracil. One of these ts mutants, clone E5-104, exhibited a more than 10(3)
      fold reduction in replication at the permissive temperature in both mouse and
      human neuroblastoma cells and lacked detectable neuroinvasiveness for highly
      sensitive immunodeficient mice. The E5-104 mutant possessed five amino acid
      substitutions in the structural protein E and one change in each of the
      nonstructural proteins NS3 and NS5. Using reverse genetics, we demonstrated that
      a Lys(46)-->Glu substitution in NS3 as well as a single Lys(315)-->Glu change in
      E significantly impaired the growth of LGT in neuroblastoma cells and reduced its
      peripheral neurovirulence for SCID mice. This study and our previous experience
      with chimeric flaviviruses indicated that a decrease in viral replication in
      neuroblastoma cells might serve as a predictor of in vivo attenuation of the
      neurotropic flaviviruses. The combination of seven mutations identified in the
      nonneuroinvasive E5-104 mutant provided a useful foundation for further
      development of a live attenuated TBEV vaccine. An evaluation of the complete
      sequence of virus recovered from brain of SCID mice inoculated with LGT mutants
      identified sites in the LGT genome that promoted
      neurovirulence/neuroinvasiveness.

PMID- 16415021
TI  - Role of helix P of the human cytomegalovirus DNA polymerase in resistance and
      hypersusceptibility to the antiviral drug foscarnet.
AB  - Mutations in the human cytomegalovirus DNA polymerase (UL54) can not only
      decrease but also increase susceptibility to the pyrophosphate (PP(i)) analogue
      foscarnet. The proximity of L802M, which confers resistance, and K805Q, which
      confers hypersusceptibility, suggests a possible unifying mechanism that affects
      drug susceptibility in one direction or the other. We found that the polymerase
      activities of L802M- and K805Q-containing mutant enzymes were literally
      indistinguishable from that of wild-type UL54; however, susceptibility to
      foscarnet was decreased or increased, respectively. A comparison with the crystal
      structure model of the related RB69 polymerase suggests that L802 and K805 are
      located in the conserved alpha-helix P that is implicated in nucleotide binding.
      Although L802 and K805 do not appear to make direct contacts with the incoming
      nucleotide, it is conceivable that changes at these residues could exert their
      effects through the adjacent, highly conserved amino acids Q807 and/or K811. Our
      data show that a K811A substitution in UL54 causes reductions in rates of
      nucleotide incorporation. The activity of the Q807A mutant is only marginally
      affected, while this enzyme shows relatively high levels of resistance to
      foscarnet. Based on these data, we suggest that L802M exerts its effects through
      subtle structural changes in alpha-helix P that affect the precise positioning of
      Q807 and, in turn, its presumptive involvement in binding of foscarnet. In
      contrast, the removal of a positive charge associated with the K805Q change may
      facilitate access or increase affinity to the adjacent Q807.

PMID- 16415022
TI  - Structure and dynamics of coxsackievirus B4 2A proteinase, an enyzme involved in
      the etiology of heart disease.
AB  - The 2A proteinases (2A(pro)) from the picornavirus family are multifunctional
      cysteine proteinases that perform essential roles during viral replication,
      involving viral polyprotein self-processing and shutting down host cell protein
      synthesis through cleavage of the eukaryotic initiation factor 4G (eIF4G)
      proteins. Coxsackievirus B4 (CVB4) 2A(pro) also cleaves heart muscle dystrophin,
      leading to cytoskeletal dysfunction and the symptoms of human acquired dilated
      cardiomyopathy. We have determined the solution structure of CVB4 2A(pro)
      (extending in an N-terminal direction to include the C-terminal eight residues of
      CVB4 VP1, which completes the VP1-2A(pro) substrate region). In terms of overall
      fold, it is similar to the crystal structure of the mature human rhinovirus
      serotype 2 (HRV2) 2A(pro), but the relatively low level (40%) of sequence
      identity leads to a substantially different surface. We show that differences in
      the cI-to-eI2 loop between HRV2 and CVB4 2A(pro) translate to differences in the
      mechanism of eIF4GI recognition. Additionally, the nuclear magnetic resonance
      relaxation properties of CVB4 2A(pro), particularly of residues G1 to S7, F64 to
      S67, and P107 to G111, reveal that the substrate region is exchanging in and out
      of a conformation in which it occupies the active site with association and
      dissociation rates in the range of 100 to 1,000 s(-1). This exchange influences
      the conformation of the active site and points to a mechanism for how self
      processing can occur efficiently while product inhibition is avoided.

PMID- 16415023
TI  - Infectious molecular clones from a simian immunodeficiency virus-infected rapid
      progressor (RP) macaque: evidence of differential selection of RP-specific
      envelope mutations in vitro and in vivo.
AB  - A minor fraction of simian immunodeficiency virus (SIV)-infected macaques
      progress rapidly to AIDS in the absence of SIV-specific immune responses. Common
      mutations in conserved residues of env in three SIVsmE543-3-infected rapid
      progressor (RP) macaques suggest the evolution of a common viral variant in RP
      macaques. The goal of the present study was to analyze the biological properties
      of these variants in vitro and in vivo through the derivation of infectious
      molecular clones. Virus isolated from a SIVsmE543-3-infected RP macaque, H445 was
      used to inoculate six naive rhesus macaques. Although RP-specific mutations
      dominated in H445 tissues, they represented only 10% of the population of the
      virus stock, suggesting a selective disadvantage in vitro. Only one of these
      macaques (H635) progressed rapidly to AIDS. Plasma virus during primary infection
      of H635 was similar to the inoculum. However, RP-specific mutations were
      apparently rapidly reselected by 4 to 9 weeks postinfection. Terminal plasma from
      H635 was used as a source of viral RNA to generate seven full-length, infectious
      molecular clones. With the exception of one clone, which was similar to SIVsmE543
      3, clones with RP-specific mutations replicated with delayed kinetics in rhesus
      peripheral blood mononuclear cells and human T-cell lines. None of the clones
      replicated in monocyte-derived or alveolar macrophages, and all used CCR5 as
      their major coreceptor. RP variants appear to be well adapted to replicate in
      vivo in RP macaques but are at a disadvantage in tissue culture compared to their
      parent, SIVsmE543-3. Therefore, tissue culture may not provide a good surrogate
      for replication of RP variants in macaques. These infectious clones will provide
      a valuable reagent to study the roles of specific viral variants in rapid
      progression in vivo.

PMID- 16415025
TI  - Canine adenovirus vectors for lung-directed gene transfer: efficacy, immune
      response, and duration of transgene expression using helper-dependent vectors.
AB  - A major hurdle to the successful clinical use of some viral vectors relates to
      the innate, adaptive, and memory immune responses that limit the efficiency and
      duration of transgene expression. Some of these drawbacks may be circumvented by
      using vectors derived from nonhuman viruses such as canine adenovirus type 2 (CAV
      2). Here, we evaluated the potential of CAV-2 vectors for gene transfer to the
      respiratory tract. We found that CAV-2 transduction was efficient in vivo in the
      mouse respiratory tract, and ex vivo in well-differentiated human pulmonary
      epithelia. Notably, the in vivo and ex vivo efficiency was poorly inhibited by
      sera from mice immunized with a human adenovirus type 5 (HAd5, a ubiquitous human
      pathogen) vector or by human sera containing HAd5 neutralizing antibodies.
      Following intranasal instillation in mice, CAV-2 vectors also led to a lower
      level of inflammatory cytokine secretion and cellular infiltration compared to
      HAd5 vectors. Moreover, CAV-2 transduction efficiency was increased in vitro in
      human pulmonary cells and in vivo in the mouse respiratory tract by FK228, a
      histone deacetylase inhibitor. Finally, by using a helper-dependent CAV-2 vector,
      we increased the in vivo duration of transgene expression to at least 3 months in
      immunocompetent mice without immunosuppression. Our data suggest that CAV-2
      vectors may be efficient and safe tools for long-term clinical gene transfer to
      the respiratory tract.

PMID- 16415024
TI  - Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3
      protein kinase and regulates nuclear localization of viral envelopment factors
      UL34 and UL31.
AB  - UL13 and Us3 are protein kinases encoded by herpes simplex virus 1. We report
      here that Us3 is a physiological substrate for UL13 in infected cells, based on
      the following observations. (i) The electrophoretic mobility, in denaturing gels,
      of Us3 isoforms from Vero cells infected with wild-type virus was slower than
      that of isoforms from cells infected with a UL13 deletion mutant virus
      (DeltaUL13). After treatment with phosphatase, the electrophoretic mobility of
      the Us3 isoforms from cells infected with wild-type virus changed, with one
      isoform migrating as fast as one of the Us3 isoforms from DeltaUL13-infected
      cells. (ii) A recombinant protein containing a domain of Us3 was phosphorylated
      by UL13 in vitro. (iii) The phenotype of DeltaUL13 resembles that of a
      recombinant virus lacking the Us3 gene (DeltaUs3) with respect to localization of
      the viral envelopment factors UL34 and UL31, whose localization has been shown to
      be regulated by Us3. UL34 and UL31 are localized in a smooth pattern throughout
      the nuclei of cells infected with wild-type virus, whereas their localization in
      DeltaUL13- and DeltaUs3-infected cells appeared as nuclear punctate patterns.
      These results indicate that UL13 phosphorylates Us3 in infected cells and
      regulates UL34 and UL31 localization, either by phosphorylating Us3 or by a Us3
      independent mechanism.

PMID- 16415026
TI  - The cellular localization pattern of Varicella-Zoster virus ORF29p is influenced
      by proteasome-mediated degradation.
AB  - Varicella-zoster virus (VZV) open reading frame 29 (ORF29) encodes a single
      stranded DNA binding protein. During lytic infection, ORF29p is localized
      primarily to infected-cell nuclei, whereas during latency it appears in the
      cytoplasm of infected neurons. Following reactivation, ORF29p accumulates in the
      nucleus. In this report, we analyze the cellular localization patterns of ORF29p
      during VZV infection and during autonomous expression. Our results demonstrate
      that ORF29p is excluded from the nucleus in a cell-type-specific manner and that
      its cellular localization pattern may be altered by subsequent expression of VZV
      ORF61p or herpes simplex virus type 1 ICP0. In these cases, ORF61p and ICP0
      induce nuclear accumulation of ORF29p in cell lines where it normally remains
      cytoplasmic. One cellular system utilized by ICP0 to influence protein abundance
      is the proteasome degradation pathway. Inhibition of the 26S proteasome, but not
      heat shock treatment, resulted in accumulation of ORF29p in the nucleus, similar
      to the effect of ICP0 expression. Immunofluorescence microscopy and pulse-chase
      experiments reveal that stabilization of ORF29p correlates with its nuclear
      accumulation and is dependent on a functional nuclear localization signal. ORF29p
      nuclear translocation in cultured enteric neurons and cells derived from an
      astrocytoma is reversible, as the protein's distribution and stability revert to
      the previous states when the proteasomal activity is restored. Thus,
      stabilization of ORF29p leads to its nuclear accumulation. Although proteasome
      inhibition induces ORF29p nuclear accumulation, this is not sufficient to
      reactivate latent VZV or target the immediate-early protein ORF62p to the nucleus
      in cultured guinea pig enteric neurons.

PMID- 16415027
TI  - High-resolution molecular and antigen structure of the VP8* core of a sialic acid
      independent human rotavirus strain.
AB  - The most intensively studied rotavirus strains initially attach to cells when the
      "heads" of their protruding spikes bind cell surface sialic acid. Rotavirus
      strains that cause disease in humans do not bind this ligand. The structure of
      the sialic acid binding head (the VP8* core) from the simian rotavirus strain RRV
      has been reported, and neutralization epitopes have been mapped onto its surface.
      We report here a 1.6-A resolution crystal structure of the equivalent domain from
      the sialic acid-independent rotavirus strain DS-1, which causes gastroenteritis
      in humans. Although the RRV and DS-1 VP8* cores differ functionally, they share
      the same galectin-like fold. Differences between the RRV and DS-1 VP8* cores in
      the region that corresponds to the RRV sialic acid binding site make it unlikely
      that DS-1 VP8* binds an alternative carbohydrate ligand in this location. In the
      crystals, a surface cleft on each DS-1 VP8* core binds N-terminal residues from a
      neighboring molecule. This cleft may function as a ligand binding site during
      rotavirus replication. We also report an escape mutant analysis, which allows the
      mapping of heterotypic neutralizing epitopes recognized by human monoclonal
      antibodies onto the surface of the VP8* core. The distribution of escape
      mutations on the DS-1 VP8* core indicates that neutralizing antibodies that
      recognize VP8* of human rotavirus strains may bind a conformation of the spike
      that differs from those observed to date.

PMID- 16415029
TI  - Mutational analysis of the herpes simplex virus triplex protein VP19C.
AB  - Herpes simplex virus type 1 (HSV-1) capsids have an icosahedral structure with
      capsomers formed by the major capsid protein, VP5, linked in groups of three by
      distinctive structures called triplexes. Triplexes are heterotrimers formed by
      two proteins in a 1:2 stoichiometry. The single-copy protein is called VP19C, and
      the dimeric protein is VP23. We have carried out insertional and deletional
      mutagenesis on VP19C and have examined the effects of the mutations on virus
      growth and capsid assembly. Insertional mutagenesis showed that the N-terminal
      approximately 100 amino acids of the protein, which correspond to a region that
      is poorly conserved among herpesviruses, are insensitive to disruption and that
      insertions into the rest of the protein had various effects on virus growth.
      Some, but not all, severely disabled mutants were compromised in the ability to
      bind VP23 or VP5. Analysis of deletion mutants revealed the presence of a nuclear
      localization signal (NLS) near the N terminus of VP19C, and this was mapped to a
      33-amino-acid region by fusion of specific sequences to a green fluorescent
      protein marker. By replacing the endogenous NLS with that from the simian virus
      40 large T antigen, we were able to show that the first 45 amino acids of VP19C
      were not essential for assembly of functional capsids and infectious virus
      particles. However, removing the first 63 amino acids resulted in formation of
      aberrant capsids and prevented virus growth, suggesting that the poorly conserved
      N-terminal sequences have some as-yet-unidentified function.

PMID- 16415028
TI  - Two domains that control prefusion stability and transport competence of the
      measles virus fusion protein.
AB  - Most viral glycoproteins mediating membrane fusion adopt a metastable native
      conformation and undergo major conformational changes during fusion. We
      previously described a panel of compounds that specifically prevent fusion
      induced by measles virus (MV), most likely by interfering with conformational
      rearrangements of the MV fusion (F) protein. To further elucidate the basis of
      inhibition and better understand the mechanism of MV glycoprotein-mediated
      fusion, we generated and characterized resistant MV variants. Spontaneous
      mutations conferring drug resistance were confirmed in transient assays and in
      the context of recombinant virions and were in all cases located in the fusion
      protein. Several mutations emerged independently at F position 462, which is
      located in the C-terminal heptad repeat (HR-B) domain. In peptide competition
      assays, all HR-B mutants at residue 462 revealed reduced affinity for binding to
      the HR-A core complex compared to unmodified HR-B. Combining mutations at residue
      462 with mutations in the distal F head region, which we had previously
      identified as mediating drug resistance, causes intracellular retention of the
      mutant proteins. The transport competence and activity of the mutants can be
      restored, however, by incubation at reduced temperature or in the presence of the
      inhibitory compounds, indicating that the F escape mutants have a reduced
      conformational stability and that the inhibitors stabilize a transport-competent
      conformation of the F trimer. The data support the conclusion that residues
      located in the head domain of the F trimer and the HR-B region contribute jointly
      to controlling F conformational stability.

PMID- 16415030
TI  - A genetic system for rhesus monkey rhadinovirus: use of recombinant virus to
      quantitate antibody-mediated neutralization.
AB  - Rhesus monkey rhadinovirus (RRV), a simian gamma-2 herpesvirus closely related to
      the Kaposi sarcoma-associated herpesvirus, replicates lytically in cultured
      rhesus monkey fibroblasts and establishes persistence in B cells. Overlapping
      cosmid clones were generated that encompass the entire 130-kilobase-pair genome
      of RRV strain 26-95, including the terminal repeat regions required for its
      replication. Cloned RRV that was produced by cotransfection of overlapping
      cosmids spanning the entire RRV26-95 genome replicated with growth kinetics and
      to titers similar to those of the parental, uncloned, wild-type RRV26-95.
      Expression cassettes for secreted-engineered alkaline phosphatase (SEAP) and
      green fluorescent protein (GFP) were inserted upstream of the R1 gene, and the
      cosmid-based system for RRV genome reconstitution was used to generate
      replication-competent, recombinant RRV that expressed either the SEAP or GFP
      reporter gene. Using the SEAP and GFP recombinant RRVs, assays were developed to
      monitor RRV infection, neutralization, and replication. Heat-inactivated sera
      from rhesus monkeys that were naturally or experimentally infected with RRV were
      assayed for their ability to neutralize RRV-SEAP and RRV-GFP infectivity using
      rhesus monkey fibroblasts. Sera from RRV-positive monkeys, but not RRV-negative
      monkeys, were consistently able to neutralize RRV infectivity when assayed by the
      production of SEAP activity or by the ability to express GFP. The neutralizing
      activity was present in the immunoglobulin fraction. Of the 17 rhesus monkeys
      tested, sera from rhesus monkey 26-95, i.e., the monkey that yielded the RRV 26
      95 isolate, had the highest titer of neutralizing activity against RRV26-95. This
      cosmid-based genetic system and the reporter virus neutralization assay will
      facilitate study of the contribution of individual RRV glycoproteins to entry
      into different cell types, particularly fibroblasts and B cells.

PMID- 16415031
TI  - Host-selected amino acid changes at the sialic acid binding pocket of the
      parvovirus capsid modulate cell binding affinity and determine virulence.
AB  - The role of receptor recognition in the emergence of virulent viruses was
      investigated in the infection of severe combined immunodeficient (SCID) mice by
      the apathogenic prototype strain of the parvovirus minute virus of mice (MVMp).
      Genetic analysis of isolated MVMp viral clones (n = 48) emerging in mice,
      including lethal variants, showed only one of three single changes (V325M, I362S,
      or K368R) in the common sequence of the two capsid proteins. As was found for the
      parental isolates, the constructed recombinant viruses harboring the I362S or the
      K368R single substitutions in the capsid sequence, or mutations at both sites,
      showed a large-plaque phenotype and lower avidity than the wild type for cells in
      the cytotoxic interaction with two permissive fibroblast cell lines in vitro and
      caused a lethal disease in SCID mice when inoculated by the natural oronasal
      route. Significantly, the productive adsorption of MVMp variants carrying any of
      the three mutations selected through parallel evolution in mice showed higher
      sensitivity to the treatment of cells by neuraminidase than that of the wild
      type, indicating a lower affinity of the viral particle for the sialic acid
      component of the receptor. Consistent with this, the X-ray crystal structure of
      the MVMp capsids soaked with sialic acid (N-acetyl neuraminic acid) showed the
      sugar allocated in the depression at the twofold axis of symmetry (termed the
      dimple), immediately adjacent to residues I362 and K368, which are located on the
      wall of the dimple, and approximately 22 A away from V325 in a threefold-related
      monomer. This is the first reported crystal structure identifying an infectious
      receptor attachment site on a parvovirus capsid. We conclude that the affinity of
      the interactions of sialic-acid-containing receptors with residues at or
      surrounding the dimple can evolutionarily regulate parvovirus pathogenicity and
      adaptation to new hosts.

PMID- 16415032
TI  - Mass spectrometric analyses of purified rhesus monkey rhadinovirus reveal 33
      virion-associated proteins.
AB  - The repertoire of proteins that comprise intact gammaherpesviruses, including the
      human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), is likely to have
      critical functions not only in viral structure and assembly but also in the early
      stages of infection and evasion of the host's rapidly deployed antiviral
      defenses. To develop a better understanding of these proteins, we analyzed the
      composition of rhesus monkey rhadinovirus (RRV), a close phylogenetic relative of
      KSHV. Unlike KSHV, RRV replicates to high titer in cell culture and thus serves
      as an effective model for studying primate gammaherpesvirus structure and virion
      proteomics. We employed two complementary mass spectrometric approaches and found
      that RRV contains at least 33 distinct virally encoded proteins. We have assigned
      7 of these proteins to the capsid, 17 to the tegument, and 9 to the envelope. Of
      the five gammaherpesvirus-specific tegument proteins, three have no known
      function. We also found three proteins not previously associated with a purified
      herpesvirus and an additional seven that represent new findings for a member of
      the gamma-2 herpesviruses. Detergent extraction resulted in particles that
      contained six distinct tegument proteins in addition to the expected capsid
      structural proteins, suggesting that this subset of tegument components may
      interact more directly with or with higher affinity for the underlying capsid
      and, in turn, may play a role in assembly or transport of viral or subviral
      particles during entry or egress.

PMID- 16415033
TI  - Papillomavirus E1 protein binds to and stimulates human topoisomerase I.
AB  - The papillomavirus (PV) E1 helicase plays a direct role in recruiting cellular
      DNA replication factors, such as replication protein A or polymerase alpha
      primase, to replicate PV genomes. Here, E1 is shown to bind to human
      topoisomerase I and stimulate its relaxation activity up to sevenfold. The
      interaction between E1 and topoisomerase I was mapped to the E1 DNA binding
      domain and C terminus. These findings imply a mechanism for the recruitment of
      topoisomerase I to PV DNA replication forks and for stimulating topoisomerase I
      to allow for efficient relaxation of the torsional stress induced by replication
      fork progression.

PMID- 16415034
TI  - Direct stimulation of translation by the multifunctional herpesvirus ICP27
      protein.
AB  - Herpes simplex virus type 1 (HSV-1) ICP27 protein is an essential regulator of
      viral gene expression with roles at various levels of RNA metabolism in the
      nucleus. Using the tethered function assay, we showed a cytoplasmic activity for
      ICP27 in directly enhancing mRNA translation in vivo in the absence of other
      viral factors. The region of ICP27 required for translational stimulation maps to
      the C terminus. Furthermore, in infected cells, ICP27 is associated with
      polyribosomes, indicating a function in translation during the lytic cycle.

PMID- 16415036
TI  - Rapid expression of human immunodeficiency virus following activation of latently
      infected cells.
AB  - The host cell activation state impacts the nature of human immunodeficiency virus
      infection. Activated cells facilitate productive infections; quiescent cells
      enable the virus to enter a latent state, the major obstacle to viral clearance.
      We wanted to understand how these differences affected viral gene expression. In
      quiescent cells activated prior to infection, viral RNA was seen 12 h
      postinfection; when cells were stimulated postinfection, viral RNA was not seen
      until 36 h postinfection. Up-regulation of viral RNA in latently infected cells
      occurred within 2 h poststimulation. This hierarchy also held true for viral
      protein production. These results may explain the rapid reemergence of viremia
      following termination of therapy.

PMID- 16415037
TI  - Identification and characterization of two internal cleavage and polyadenylation
      sites of parvovirus B19 RNA.
AB  - Polyadenylation of B19 pre-mRNAs at the major internal site, (pA)p1, is
      programmed by the nonconsensus core cleavage and polyadenylation specificity
      factor-binding hexanucleotide AUUAAA. Efficient use of this element requires both
      downstream and upstream cis-acting elements and is further influenced by an
      adjacent AAUAAC motif. The primary hexanucleotide element must be nonconsensus to
      allow efficient readthrough of P6-generated pre-mRNAs into the capsid-coding
      region. An additional cleavage and polyadenylation site, (pA)p2, 296 nucleotides
      downstream of (pA)p1 was shown to be used following both B19 infection and
      transfection of a genomic clone. RNAs polyadenylated at (pA)p2 comprise
      approximately 10% of B19 RNAs that are polyadenylated internally.

PMID- 16415035
TI  - A gammaherpesvirus 68 gene 50 null mutant establishes long-term latency in the
      lung but fails to vaccinate against a wild-type virus challenge.
AB  - The gammaherpesvirus immediate-early genes are critical regulators of virus
      replication and reactivation from latency. Rta, encoded by gene 50, serves as the
      major transactivator of the lytic program and is highly conserved among all the
      gammaherpesviruses, including Epstein-Barr virus, Kaposi's sarcoma-associated
      herpesvirus, and murine gammaherpesvirus 68 (gammaHV68). Introduction of a
      translation stop codon in gammaHV68 gene 50 (gene 50.stop gammaHV68) demonstrated
      that Rta is essential for virus replication in vitro. To investigate the role
      that virus replication plays in the establishment and maintenance of latency, we
      infected mice with gene 50.stop gammaHV68. Notably, the gene 50.stop virus
      established a long-term infection in lung B cells following intranasal infection
      of mice but was unable to establish latency in the spleen. This complete block in
      the establishment of latency in the spleen was also seen when lytic virus
      production was inhibited by treating mice infected with wild-type virus with the
      antiviral drug cidofovir, implicating virus replication and not an independent
      function of Rta in the establishment of splenic latency. Furthermore, we showed
      that gene 50.stop gammaHV68 was unable to prime the immune system and was unable
      to protect against a challenge with wild-type gammaHV68, despite its ability to
      chronically infect lung B cells. These data indicate gammaherpesviruses that are
      unable to undergo lytic replication in vivo may not be viable vaccine candidates
      despite the detection of cells harboring viral genome at late times
      postinfection.

PMID- 16415038
TI  - Egress of alphaherpesviruses.

PMID- 16415039
TI  - Reduction of broad-spectrum antibiotic use with computerized decision support in
      an intensive care unit.
AB  - OBJECTIVE: To implement and evaluate the effect of a computerized decision
      support tool on antibiotic use in an intensive care unit (ICU). DESIGN:
      Prospective before-and-after cohort study. SETTING: Twenty-four bed tertiary
      hospital adult medical/surgical ICU. PARTICIPANTS: All consecutive patients from
      May 2001 to November 2001 (N = 524) and March 2002 to September 2002 (N = 536).
      INTERVENTION: A real-time microbiology browser and computerized decision support
      system for isolate directed antibiotic prescription. MAIN OUTCOME MEASURES:
      Number of courses of antibiotic prescribed, antibiotic utilization (defined daily
      doses (DDDs)/100 ICU bed-days), antibiotic susceptibility mismatches, and system
      uptake. RESULTS: There was a significant reduction in the proportion of patients
      prescribed carbapenems [odds ratio (OR) = 0.61, 95% confidence interval (CI) =
      0.39-0.97, P = 0.04], third-generation cephalosporins (OR = 0.58, 95% CI = 0.42
      0.79, P = 0.001), and vancomycin (OR = 0.67, 95% CI = 0.45-1.00, P = 0.05) after
      adjustment for risk factors including Apache II score, suspected infection,
      positive microbiology, intubation, and length of stay. The decision support tool
      was associated with a 10.5% reduction in both total antibiotic utilization (166
      149 DDDs/100 ICU bed days) and the highest volume broad-spectrum antibiotics.
      There were fewer susceptibility mismatches for initial antibiotic therapy (OR =
      0.63, 95% CI = 0.39-0.98, P = 0.02) and increased de-escalation to narrower
      spectrum antibiotics. Uptake of the program was high with 6028 access episodes
      during the 6-month evaluation period. CONCLUSIONS: This tool streamlined
      collation and clinical use of microbiology results and integrated into the daily
      ICU workflow. Its introduction was accompanied by a reduction in both total and
      broad-spectrum antibiotic use and an increase in the number of switches to
      narrower spectrum antibiotics.

PMID- 16415040
TI  - Mild Nijmegen breakage syndrome phenotype due to alternative splicing.
AB  - Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage
      syndrome (NBS), characterized by microcephaly, chromosomal instability,
      radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of
      NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin;
      however, 10 further truncating mutations have been identified in patients of
      other ethnic origin. Partially functional proteins produced by alternative
      initiation of translation, and possibly diminishing the severity of the NBS
      phenotype, have been described for several NBS1 mutations. Here, we report a 53
      year-old NBS patient, homozygous for the NBS1 mutation, 742insGG, in exon 7 and
      who presents with a particularly mild phenotype. In an attempt to find a
      potential molecular explanation for the mild phenotype observed, we carried out a
      conventional semi-quantitative and quantitative RT-PCR analyses which revealed
      two transcripts of almost equal amounts in the patient and her parents--the
      expected full-length transcript carrying the 742insGG mutation and a second
      transcript with deleted exons 6 and 7. The transcript was also observed in
      controls and other NBS patients, however, at quantities more than 100-fold lower
      than that in the patient described here. Because the skipping of exons 6 and 7
      results in an internal in-frame deletion, which eliminates the truncating GG
      insertion, we propose that this transcript may code for a partially functional
      protein of approximately 70 kDa that could be responsible for the unusually mild
      NBS phenotype observed in this patient. Indeed, complementation analysis of null
      mutant mouse cells indicates that the alternatively spliced mRNA codes for a
      protein with significant functional capacity.

PMID- 16415041
TI  - Genetic variation in DTNBP1 influences general cognitive ability.
AB  - Human intelligence is a trait that is known to be significantly influenced by
      genetic factors, and recent linkage data provide positional evidence to suggest
      that a region on chromosome 6p, previously associated with schizophrenia, may be
      linked to variation in intelligence. The gene for dysbindin-1 (DTNBP1) is located
      at 6p and has also been implicated in schizophrenia, a neuropsychiatric disorder
      characterized by cognitive dysfunction. We report an association between DTNBP1
      genotype and general cognitive ability (g) in two independent cohorts, including
      213 patients with schizophrenia or schizo-affective disorder and 126 healthy
      volunteers. These data suggest that DTNBP1 genetic variation influences human
      intelligence.

PMID- 16415042
TI  - Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan
      type familial partial lipodystrophy.
AB  - Mutations in the LMNA gene encoding A-type lamins cause several diseases,
      including Emery-Dreifuss muscular dystrophy and Dunnigan-type familial partial
      lipodystrophy (FPLD). We analyzed differentiation of 3T3-L1 preadipocytes to
      adipocytes in cells overexpressing wild-type lamin A as well as lamin A with
      amino acid substitutions at position 482 that cause FPLD. We also examined
      adipogenic conversion of mouse embryonic fibroblasts lacking A-type lamins.
      Overexpression of both wild-type and mutant lamin A inhibited lipid accumulation,
      triglyceride synthesis and expression of adipogenic markers. This was associated
      with inhibition of expression of peroxisome-proliferator-activated receptor gamma
      2 (PPARgamma2) and Glut4. In contrast, embryonic fibroblasts lacking A-type
      lamins accumulated more intracellular lipid and exhibited elevated de novo
      triglyceride synthesis compared with wild-type fibroblasts. They also had
      increased basal phosphorylation of AKT1, a mediator of insulin signaling. We
      conclude that A-type lamins act as inhibitors of adipocyte differentiation,
      possibly by affecting PPARgamma2 and insulin signaling.

PMID- 16415043
TI  - Frame shuffling: a novel method for in vitro protein evolution.
AB  - We describe 'frame shuffling', a novel method for preparing artificial protein
      libraries. With this method, a Y-family DNA polymerase known to introduce frame
      shift mutations at high rates is utilized to scramble the reading frames of a
      parental gene. The resultant progeny produce mutant proteins having segmental
      sequence changes. Such frame-shuffled mutant proteins exhibit physicochemical
      properties that differ from those of proteins obtained using conventional
      mutagenesis.

PMID- 16415044
TI  - Morphological and functional analysis of Rac1B in Dictyostelium discoideum.
AB  - Rac1B, a small GTP-binding protein in Dictyostelium discoideum, is involved in
      regulation of the actin cytoskeleton. Scanning electron microscopy revealed
      distinctive phenotypes for the wild-type, constitutively active, constitutively
      inactive and overexpressing cell lines. Immunofluorescence showed constitutively
      active Rac1B localized to lamellipodia and sites of cell-to-cell contact. In
      contrast, constitutively inactive Rac1B was homogeneously distributed throughout
      the cell. Phalloidin staining demonstrated that active Rac1B co-localizes with F
      actin. Amoebae expressing mutant Rac1B exhibited defects in endocytosis,
      cytokinesis and multicellular development. Overexpression of wild-type Rac1B
      positively affected fluid-phase endocytosis, whereas expression of either
      constitutively active or inactive forms of Rac1B inhibited endocytic rates. The
      greatest defects in cytokinesis were observed in amoebae producing constitutively
      active Rac1B or overexpressing wild-type Rac1B. These cells were severely
      multinucleated and divided by traction-mediated cytofission when placed onto a
      solid surface. Cells expressing mutant Rac1B were unable to form viable fruiting
      bodies. Elucidating the role of Rac1B in filamentous actin dynamics will lead to
      a better understanding of cell adhesion, development and cell motility.

PMID- 16415045
TI  - On the origin of HOLZ lines splitting near interfaces: multislice simulation of
      CBED patterns.
AB  - Splitting of HOLZ lines on CBED patterns is systematically observed at the
      proximity of interfaces and prevents local strain measurements by monitoring of
      line shifts. It was previously suggested that such splitting occurs due to
      interface-strain relaxation in thin TEM lamella. Here we confirm this model by
      dynamical simulation of CBED patterns using the multislice algorithm.

PMID- 16415046
TI  - Development of a magnetizing stage for in situ observations with electron
      holography and Lorentz microscopy.
AB  - A magnetizing stage, by which approximately horizontal magnetic fields can be
      applied to thin-foiled specimens, has been developed so that magnetization
      process can be observed in situ with electron holography and Lorentz microscopy.
      It is possible to apply magnetic field up to 200 Oe without serious image
      distortion by utilizing the magnetizing stage, beam-deflection-back coils and a
      magnetically shielded objective lens. The devised system can be used to studies
      of magnetization processes in many soft magnets.

PMID- 16415047
TI  - Characterization and application of a new optical probe for membrane lipid
      domains.
AB  - In this article, we characterize the fluorescence of an environmentally sensitive
      probe for lipid membranes, di-4-ANEPPDHQ. In large unilamellar lipid vesicles
      (LUVs), its emission spectrum shifts up to 30 nm to the blue with increasing
      cholesterol concentration. Independently, it displays a comparable blue shift in
      liquid-ordered relative to liquid-disordered phases. The cumulative effect is a
      60-nm difference in emission spectra for cholesterol containing LUVs in the
      liquid-ordered state versus cholesterol-free LUVs in the liquid-disordered phase.
      Given these optical properties, we use di-4-ANEPPDHQ to image the phase
      separation in giant unilamellar vesicles with both linear and nonlinear optical
      microscopy. The dye shows green and red fluorescence in liquid-ordered and 
      disordered domains, respectively. We propose that this reflects the relative
      rigidity of the molecular packing around the dye molecules in the two phases. We
      also observe a sevenfold stronger second harmonic generation signal in the liquid
      disordered domains, consistent with a higher concentration of the dye resulting
      from preferential partitioning into the disordered phase. The efficacy of the dye
      for reporting lipid domains in cell membranes is demonstrated in polarized
      migrating neutrophils.

PMID- 16415048
TI  - Conditions for propagation and block of excitation in an asymptotic model of
      atrial tissue.
AB  - Detailed ionic models of cardiac cells are difficult for numerical simulations
      because they consist of a large number of equations and contain small parameters.
      The presence of small parameters, however, may be used for asymptotic reduction
      of the models. Earlier results have shown that the asymptotics of cardiac
      equations are nonstandard. Here we apply such a novel asymptotic method to an
      ionic model of human atrial tissue to obtain a reduced but accurate model for the
      description of excitation fronts. Numerical simulations of spiral waves in atrial
      tissue show that wave fronts of propagating action potentials break up and self
      terminate. Our model, in particular, yields a simple analytical criterion of
      propagation block, which is similar in purpose but completely different in nature
      to the "Maxwell rule" in the FitzHugh-Nagumo type models. Our new criterion
      agrees with direct numerical simulations of breakup of reentrant waves.

PMID- 16415049
TI  - A model of the roles of essential kinases in the induction and expression of late
      long-term potentiation.
AB  - The induction of late long-term potentiation (L-LTP) involves complex
      interactions among second-messenger cascades. To gain insights into these
      interactions, a mathematical model was developed for L-LTP induction in the CA1
      region of the hippocampus. The differential equation-based model represents
      actions of protein kinase A (PKA), MAP kinase (MAPK), and CaM kinase II (CAMKII)
      in the vicinity of the synapse, and activation of transcription by CaM kinase IV
      (CAMKIV) and MAPK. L-LTP is represented by increases in a synaptic weight.
      Simulations suggest that steep, supralinear stimulus-response relationships
      between stimuli (e.g., elevations in [Ca(2+)]) and kinase activation are
      essential for translating brief stimuli into long-lasting gene activation and
      synaptic weight increases. Convergence of multiple kinase activities to induce L
      LTP helps to generate a threshold whereby the amount of L-LTP varies steeply with
      the number of brief (tetanic) electrical stimuli. The model simulates tetanic, 
      burst, pairing-induced, and chemical L-LTP, as well as L-LTP due to synaptic
      tagging. The model also simulates inhibition of L-LTP by inhibition of MAPK,
      CAMKII, PKA, or CAMKIV. The model predicts results of experiments to delineate
      mechanisms underlying L-LTP induction and expression. For example, the cAMP
      antagonist RpcAMPs, which inhibits L-LTP induction, is predicted to inhibit ERK
      activation. The model also appears useful to clarify similarities and differences
      between hippocampal L-LTP and long-term synaptic strengthening in other systems.

PMID- 16415050
TI  - Searching for the molecular arrangement of transmembrane ceramide channels.
AB  - Ceramides have been implicated in the initiation of apoptosis by permeabilizing
      the mitochondrial outer membrane to small proteins, including cytochrome c. In
      addition, ceramides were shown to form large metastable channels in planar
      membranes and liposomes, indicating that these lipids permeabilize membranes
      directly. Here we analyze molecular models of ceramide channels and test their
      stability in molecular dynamics simulations. The structural units are columns of
      four to six ceramides H-bonded via amide groups and arranged as staves in either
      a parallel or antiparallel manner. Two cylindrical assemblies of 14 columns (four
      or six molecules per column) were embedded in a fully hydrated palmitoyloleoyl
      phosphatidylcholine phospholipid bilayer, and simulated for 24 ns in total. After
      equilibration, the water-filled pore adopted an hourglass-like shape as
      headgroups of ceramides and phospholipids formed a smooth continuous interface.
      The structure-stabilizing interactions were both hydrogen bonds between the
      headgroups (including water-mediated interactions) and packing of the hydrocarbon
      tails. Ceramide's essential double bond reduced the mobility of the hydrocarbon
      tails and stabilized their packing. The six-column assembly remained stable
      throughout a 10-ns simulation. During simulations of four-column assemblies,
      pairs of columns displayed the tendency of splitting out from the channels,
      consistent with the previously proposed mechanism of channel disassembly.

PMID- 16415051
TI  - Atomistic simulation approach to a continuum description of self-assembled beta
      sheet filaments.
AB  - We investigated the supramolecular structure and continuum mechanical properties
      of a beta-sheet nanofiber comprised of a self-assembling peptide ac-[RARADADA]2
      am using computer simulations. The supramolecular structure was determined by
      constructing candidate filaments with dimensions compatible with those observed
      in atomic force microscopy and selecting the most stable ones after running
      molecular dynamics simulations on each of them. Four structures with different
      backbone hydrogen-bonding patterns were identified to be similarly stable. We
      then quantified the continuum mechanical properties of these identified
      structures by running three independent simulations: thermal motion analysis,
      normal mode analysis, and steered molecular dynamics. Within the range of
      deformations investigated, the filament showed linear elasticity in transverse
      directions with an estimated persistence length of 1.2-4.8 microm. Although side
      chain interactions govern the propensity and energetics of filament self
      assembly, we found that backbone hydrogen-bonding interactions are the primary
      determinant of filament elasticity, as demonstrated by its effective thickness,
      which is smaller than that estimated by atomic force microscopy or from the
      molecular geometry, as well as by the similar bending stiffness of a model
      filament without charged side chains. The generality of our approach suggests
      that it should be applicable to developing continuum elastic ribbon models of
      other beta-sheet filaments and amyloid fibrils.

PMID- 16415052
TI  - Improvement in motion efficiency of the spirochete Brachyspira pilosicoli in
      viscous environments.
AB  - Spirochetes are unique among swimming bacteria in terms of their lack of external
      flagella. They actively move in viscous environments, and, surprisingly, the
      swimming speed of the spirochete Leptospira interrogans has been reported to
      increase with viscosity in methylcellulose solutions. Many researchers consider
      that the presence of a loose, quasi-rigid network formed by linear polymer
      molecules is related to this strange phenomenon. One of the authors has proposed
      a theory that expresses this idea mathematically and successfully explains the
      speed properties of an externally flagellated bacterium in viscous environments.
      This theory predicts that the ratio of swimming speed to wave frequency (v/f
      ratio, motion efficiency in a sense) increases with viscosity. In this study, we
      demonstrated a new method of measuring the swimming speed and wave frequency of
      spirochetes and the motion characteristics of a swine intestinal spirochete,
      Brachyspira pilosicoli strain NK1f, measured in viscous environments. Several
      sets of swimming speed and wave frequency data were simultaneously derived from
      an animation obtained by our method. The v/f ratio of NK1f displayed a tendency
      to increase with increasing viscosity, suggesting the validity of the above
      mentioned theory. Improvement of motion efficiency is at least one of the factors
      that maintain spirochete motility in viscous environments.

PMID- 16415054
TI  - Role of protein flexibility in ion permeation: a case study in gramicidin A.
AB  - Proteins have a flexible structure, and their atoms exhibit considerable
      fluctuations under normal operating conditions. However, apart from some enzyme
      reactions involving ligand binding, our understanding of the role of flexibility
      in protein function remains mostly incomplete. Here we investigate this question
      in the realm of membrane proteins that form ion channels. Specifically, we
      consider ion permeation in the gramicidin A channel, and study how the energetics
      of ion conduction changes as the channel structure is progressively changed from
      completely flexible to a fixed one. For each channel structure, the potential of
      mean force for a permeating potassium ion is determined from molecular dynamics
      (MD) simulations. Using the same molecular dynamics data for completely flexible
      gramicidin A, we also calculate the average densities and fluctuations of the
      peptide atoms and investigate the correlations between these fluctuations and the
      motion of a permeating ion. Our results show conclusively that peptide
      flexibility plays an important role in ion permeation in the gramicidin A
      channel, thus providing another reason--besides the well-known problem with the
      description of single file pore water--why this channel cannot be modeled using
      continuum electrostatics with a fixed structure. The new method developed here
      for studying the role of protein flexibility on its function clarifies the
      contributions of the fluctuations to energy and entropy, and places limits on the
      level of detail required in a coarse-grained model.

PMID- 16415055
TI  - The amplitude distribution of release events through a fusion pore.
AB  - Neurotransmitters, hormones, or dyes may be released from vesicles via a fusion
      pore, rather than by full fusion of the vesicle with the plasma membrane. If the
      lifetime of the fusion pore is comparable to the time required for the substance
      to exit the vesicle, only a fraction of the total vesicle content may be released
      during a single pore opening. Assuming 1), fusion pore lifetimes are
      exponentially distributed (tauP), as expected for simple single channel openings,
      and 2), vesicle contents are lost through the fusion pore with an exponential
      time course (tauD), we derive an analytical expression for the probability
      density function of the fraction of vesicle content released (F): dP/dF=A (1-F)(A
      1), where A=tauD/tauP. If A>1, the maximum of the distribution is at F=0; if A<1,
      the maximum is at F=1; if A=1, the distribution is perfectly flat. Thus, the
      distribution never has a peak in the middle (0<F<1). This should be considered
      when interpreting the distribution of miniature synaptic currents, or the
      fraction of FM dye molecules lost during a single fusion pore opening event.

PMID- 16415053
TI  - Revealing the topography of cellular membrane domains by combined atomic force
      microscopy/fluorescence imaging.
AB  - Simultaneous atomic force microscopy (AFM) and confocal fluorescence imaging were
      used to observe in aqueous buffer the three-dimensional landscape of the inner
      surface of membrane sheets stripped from fixed tumor mast cells. The AFM images
      reveal prominent, irregularly shaped raised domains that label with fluorescent
      markers for both resting and activated immunoglobin E receptors (FcepsilonRI), as
      well as with cholera toxin-aggregated GM1 and clathrin. The latter suggests that
      coated pits bud from these regions. These features are interspersed with flatter
      regions of membrane and are frequently surrounded and interconnected by
      cytoskeletal assemblies. The raised domains shrink in height by approximately 50%
      when cholesterol is extracted with methyl-beta-cyclodextrin. Based on
      composition, the raised domains seen by AFM correspond to the cholesterol
      enriched dark patches observed in transmission electron microscopy (TEM). These
      patches were previously identified as sites of signaling and endocytosis based on
      their localization of activated FcepsilonRI, at least 10 associated signaling
      molecules, and the presence of clathrin-coated pits. Overall the data suggest
      that signaling and endocytosis occur in mast cells from raised membrane regions
      that depend on cholesterol for their integrity and may be organized in specific
      relationship with the cortical cytoskeleton.

PMID- 16415057
TI  - Dynamics of the C-terminal region of TnI in the troponin complex in solution.
AB  - The determination of crystal structures of the troponin complex (Takeda et al.
      2003. Nature. 424:35-41; Vinogradova et al. 2005. Proc. Natl. Acad. Sci. USA.
      102:5038-5043) has advanced knowledge of the regulation of muscle contraction at
      the molecular level. However, there are domains important for actin binding that
      are not visualized. We present evidence that the C-terminal region of troponin I
      (TnI residues 135-182) is flexible in solution and has no stable secondary
      structure. We use NMR spectroscopy to observe the backbone dynamics of skeletal
      [2H, 13C, 15N]-TnI in the troponin complex in the presence of Ca2+ or EGTA/Mg2+.
      Residues in this region give stronger signals than the remainder of TnI, and
      chemical shift index values indicate little secondary structure, suggesting a
      very flexible region. This is confirmed by NMR relaxation measurements. Unlike
      TnC and other regions of TnI in the complex, the C-terminal region of TnI is not
      affected by Ca2+ binding. Relaxation measurements and reduced spectral density
      analysis are consistent with the C-terminal region of TnI being a tethered domain
      connected to the rest of the troponin complex by a flexible linker, residues 137
      146, followed by a collapsed region with at most nascent secondary structure.

PMID- 16415056
TI  - Deterministic model of dermal wound invasion incorporating receptor-mediated
      signal transduction and spatial gradient sensing.
AB  - During dermal wound healing, platelet-derived growth factor (PDGF) serves as both
      a chemoattractant and mitogen for fibroblasts, potently stimulating their
      invasion of the fibrin clot over a period of several days. A mathematical model
      of this process is presented, which accurately accounts for the sensitivity of
      PDGF gradient sensing through PDGF receptor/phosphoinositide 3-kinase-mediated
      signal transduction. Analysis of the model suggests that PDGF receptor-mediated
      endocytosis and degradation of PDGF allows a constant PDGF concentration profile
      to be maintained at the leading front of the fibroblast density profile as it
      propagates, at a constant rate, into the clot. Thus, the constant PDGF gradient
      can span the optimal concentration range for asymmetric phosphoinositide 3-kinase
      signaling and fibroblast chemotaxis, with near-maximal invasion rates elicited
      over a relatively broad range of PDGF secretion rates. A somewhat surprising
      finding was that extremely sharp PDGF gradients do not necessarily stimulate
      faster progression through the clot, because maintaining such a gradient through
      PDGF consumption is a potentially rate-limiting process.

PMID- 16415058
TI  - Molecular dynamics studies of the archaeal translocon.
AB  - The translocon is a protein-conducting channel conserved over all domains of life
      that serves to translocate proteins across or into membranes. Although this
      channel has been well studied for many years, the recent discovery of a high
      resolution crystal structure opens up new avenues of exploration. Taking
      advantage of this, we performed molecular dynamics simulations of the translocon
      in a fully solvated lipid bilayer, examining the translocation abilities of
      monomeric SecYEbeta by forcing two helices comprised of different amino acid
      sequences to cross the channel. The simulations revealed that the so-called plug
      of SecYEbeta swings open during translocation, closing thereafter. Likewise, it
      was established that the so-called pore ring region of SecYEbeta forms an
      elastic, yet tight, seal around the translocating oligopeptides. The closed state
      of the channel was found to block permeation of all ions and water molecules; in
      the open state, ions were blocked. Our results suggest that the SecYEbeta monomer
      is capable of forming an active channel.

PMID- 16415060
TI  - Oligomerization and aggregation of bovine pancreatic ribonuclease A:
      characteristic events observed by FTIR spectroscopy.
AB  - Nonnative protein aggregation, which is a common feature in biotechnology, is
      also a clinical feature in more than 20 serious degenerative diseases. We studied
      the specific events of bovine pancreatic ribonuclease A thermal aggregation by a
      combination of second derivative infrared analysis and two-dimensional infrared
      correlation spectroscopy. By comparing the events that occur in reversible and
      irreversible thermal unfolding processes, certain events that were related to
      protein aggregation were characterized. Particularly, a band that appeared at
      high temperatures was assigned to the cross beta-structures in oligomers. The
      effect of pH, NaCl, and ethanol on ribonuclease A oligomerization as well as
      further aggregation induced by heat were studied and dissimilar effects of these
      additives were found. Basic pH and NaCl could accelerate the thermal aggregation
      but did not affect the formation of oligomers, whereas ethanol could increase
      both the aggregation rate and the population of oligomers. Our results suggested
      that the aggregation of RNase A might be initiated by hydrophobic interactions,
      controlled by oligomerization and mediated by electrostatic interactions.
      Moreover, the strategy of using second derivative and two-dimensional infrared
      analysis might provide a potential powerful tool to study the events that are
      directly related to the initiation of protein aggregation.

PMID- 16415059
TI  - Local structural preferences and dynamics restrictions in the urea-denatured
      state of SUMO-1: NMR characterization.
AB  - We have investigated by multidimensional NMR the structural and dynamic
      characteristics of the urea-denatured state of activated SUMO-1, a 97-residue
      protein belonging to the growing family of ubiquitin-like proteins involved in
      post-translational modifications. Complete backbone amide and 15N resonance
      assignments were obtained in the denatured state by using HNN and HN(C)N
      experiments. These enabled other proton assignments from TOCSY-HSQC spectra.
      Secondary Halpha chemical shifts and 1H-1H NOE indicate that the protein chain in
      the denatured state has structural preferences in the broad beta-domain for many
      residues. Several of these are seen to populate the (phi,psi) space belonging to
      polyproline II structure. Although there is no evidence for any persistent
      structures, many contiguous stretches of three or more residues exhibit
      structural propensities suggesting possibilities of short-range transient
      structure formation. The hetero-nuclear 1H-15N NOEs are extremely weak for most
      residues, except for a few at the C-terminal, and the 15N relaxation rates show
      sequence-wise variation. Some of the regions of slow motions coincide with those
      of structural preferences and these are interspersed by highly flexible residues.
      The implications of these observations for the early folding events starting from
      the urea-denatured state of activated SUMO-1 have been discussed.

PMID- 16415062
TI  - Probing surface structures of Shewanella spp. by microelectrophoresis.
AB  - Long-range electrostatic forces substantially influence bacterial interactions
      and bacterial adhesion during the preliminary steps of biofilm formation. The
      strength of these forces depends strongly on the structure of the bacterium
      surfaces investigated. The latter may be addressed from appropriate analysis of
      electrophoretic mobility measurements. Due to the permeable character of the
      bacterium wall and/or surrounding polymer layer, bacteria may be regarded as
      paradigms of soft bioparticles. The electrophoretic motion of such particles in a
      direct-current electric field differs considerably from that of their rigid
      counterparts in the sense that electroosmotic flow takes place around and within
      the soft surface layer. Recent developments of electrokinetic theories for soft
      particles now render possible the evaluation of the softness degree (or
      equivalently the hydrodynamic permeability) from the raw electrokinetic data. In
      this article, the electrophoretic mobilities of three Shewanella strains (MR-4,
      CN32, and BrY) presenting various and well-characterized phenotypes of polymer
      fringe are reported over a wide range of pH and ionic strength conditions. The
      data are quantitatively analyzed on the basis of a rigorous numerical evaluation
      of the governing electrostatic and hydrodynamic equations for soft particles. It
      is clearly shown how the peculiar surface structures of the bacteria investigated
      are reflected in their electrohydrodynamic properties.

PMID- 16415063
TI  - Action spectrum of photoinhibition in leaves of wild type and npq1-2 and npq4-1
      mutants of Arabidopsis thaliana.
AB  - Photoinhibition is light-induced inactivation of PSII. Hypotheses about the
      photoreceptor(s) of photoinhibition include the Chl antenna of PSII, manganese of
      the oxygen-evolving complex (OEC), uncoupled Chl and iron-sulfur centres. We
      measured the action spectrum of photoinhibition in vivo from wild-type
      Arabidopsis thaliana L. and from the npq1-2 and npq4-1 mutants defective in non
      photochemical quenching (NPQ) of excitations of the PSII antenna. The in vivo
      action spectrum was found to resemble closely the in vitro action spectra
      published for photoinhibition. We compared the action spectrum with absorbance
      spectra of model compounds of the OEC complex and other potential photoreceptors
      of photoinhibition. The comparison suggests that both manganese and Chl function
      as photoreceptors in photoinhibition. In accordance with the function of two
      types of photoreceptors in photoinhibition, NPQ was found to offer only partial
      protection against photoinhibition at visible wavelengths. The low protective
      efficiency of NPQ supports the conclusion that the Chl antenna of PSII is not the
      only photoreceptor of photoinhibition. Comparison of the action spectrum of
      photoinhibition with the emission spectrum of sunlight shows that the UV part of
      sunlight is responsible for the major part of photoinhibition under natural
      conditions.

PMID- 16415061
TI  - Micro- and macrorheological properties of actin networks effectively cross-linked
      by depletion forces.
AB  - The structure and rheology of cytoskeletal networks are regulated by actin
      binding proteins. Aside from these specific interactions, depletion forces can
      also alter the properties of cytoskeletal networks. Here we demonstrate that the
      addition of poly(ethylene glycol) (PEG) as a depletion agent results not only in
      severe structural changes, but also in alterations in mechanical properties of
      actin solutions. In the plateau of the elastic modulus two regimes can be
      distinguished by micro and macrorheological methods. In the first, the elastic
      modulus increases only slightly with increasing depletion agent, whereas above a
      critical concentration c*, a strong increase of cPEG6k3.5 is observed in a
      distinct second regime. Microrheological data and electron microscopy images show
      a homogenous network of actin filaments in the first regime, whereas at higher
      PEG concentrations a network of actin bundles is observed. The concentration
      dependence of the plateau modulus G0, the shift in entanglement time taue, and
      the nonlinear response indicate that below c* the network becomes effectively
      cross-linked, whereas above c* G0(cPEG6k) is primarily determined by the network
      of bundles that exhibits a linearly increasing bundle thickness.

PMID- 16415064
TI  - Contribution of fructose-1,6-bisphosphatase and sedoheptulose-1,7-bisphosphatase
      to the photosynthetic rate and carbon flow in the Calvin cycle in transgenic
      plants.
AB  - To clarify the contributions of fructose-1,6-bisphosphatase (FBPase) and
      sedoheptulose-1,7-bisphosphatase (SBPase) separately to the carbon flux in the
      Calvin cycle, we generated transgenic tobacco plants expressing cyanobacterial
      FBPase-II in chloroplasts (TpF) or Chlamydomonas SBPase in chloroplasts (TpS). In
      TpF-11 plants with 2.3-fold higher FBPase activity and in TpS-11 and TpS-10
      plants with 1.6- and 4.3-fold higher SBPase activity in chloroplasts compared
      with the wild-type plants, the amount of final dry matter was approximately 1.3-,
      1.5- and 1.5-fold higher, respectively, than that of the wild-type plants. At
      1,500 micromol m(-2) s(-1), the photosynthetic activities of TpF-11, TpS-11 and
      TpS-10 were 1.15-, 1.27- and 1.23-fold higher, respectively, than that of the
      wild-type plants. The in vivo activation state of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) and the level of ribulose-1,5-bisphosphate (RuBP)
      in TpF-11, TpS-10 and TpS-11 were significantly higher than those in the wild
      type plants. However, the transgenic plant TpF-9 which had a 1.7-fold higher
      level of FBPase activity showed the same phenotype as the wild-type plant, except
      for the increase of starch content in the source leaves. TpS-11 and TpS-10 plants
      with 1.6- and 4.3-fold higher SBPase activity, respectively, showed an increase
      in the photosynthetic CO(2) fixation, growth rate, RuBP contents and Rubisco
      activation state, while TpS-2 plants with 1.3-fold higher SBPase showed the same
      phenotype as the wild-type plants. These data indicated that the enhancement of
      either a >1.7-fold increase of FBPase or a 1.3-fold increase of SBPase in the
      chloroplasts had a marked positive effect on photosynthesis, that SBPase is the
      most important factor for the RuBP regeneration in the Calvin cycle and that
      FBPase contributes to the partitioning of the fixed carbon for RuBP regeneration
      or starch synthesis.

PMID- 16415065
TI  - Characterization of the preprotein translocon at the outer envelope membrane of
      chloroplasts by blue native PAGE.
AB  - The preprotein translocon at the outer envelope membrane of chloroplasts (Toc)
      mediates the recognition and import of nuclear-encoded preproteins into
      chloroplasts. Two receptor components, Toc159 and Toc34, and the channel Toc75
      form the Toc complex. In this study, we have analyzed the molecular architecture
      and organization of the Toc complex by blue native PAGE (BN-PAGE), which is a
      high-resolution method for separating membrane protein complexes under non
      denaturing conditions. Pea chloroplasts isolated in the presence of a protease
      inhibitor cocktail were directly solubilized in detergent solution and analyzed
      by BN-PAGE and size exclusion chromatography. Subsequent immunoblot analyses
      indicated that the complex composed of Toc75, Toc159 and Toc34 has a molecular
      mass of 800-1,000 kDa. Limited proteolysis revealed a core of the Toc complex,
      which was resistant to proteases and detergent treatments. The stoichiometry of
      the three Toc proteins was calculated as approximately 1 : 3 : 3 between Toc159 :
      Toc75 : Toc34. We have also analyzed the Toc complex of etioplasts and root
      plastids. These plastids were found to have essentially the same sized Toc
      complex as that of the chloroplast.

PMID- 16415066
TI  - Loss of AtPDR8, a plasma membrane ABC transporter of Arabidopsis thaliana, causes
      hypersensitive cell death upon pathogen infection.
AB  - Plants contain a large number of ATP-binding cassette (ABC) transporters
      belonging to different subclasses. AtPDR8 is the only member of the pleiotropic
      drug resistance (PDR) ABC transporter subclass in Arabidopsis that is
      constitutively highly expressed. In transgenic Arabidopsis plants harboring the
      AtPDR8 promoter fused to beta-glucuronidase (GUS), reporter expression was shown
      to be strong in the stomata and hydathode. In the stomata, transcripts of AtPDR8
      were particularly frequent in the cells surrounding air spaces. Subcellular
      fractionation and immunochemical analysis showed that AtPDR8 was localized in the
      plasma membrane. When a knockout mutant of AtPDR8 (atpdr8) was infected with
      bacterial and oomycete pathogens, the plants exhibited chlorotic lesions and a
      hypersensitive response (HR)-like cell death. Cell death was detected in the
      atpdr8 mutants within 10 h of infection with the virulent bacterial pathogen,
      Pseudomonas syringae. As a result, the growth of P. syringae in the leaves of the
      atpdr8 mutant was reduced to 1% of that in the wild type. The defense response
      genes, PR-1, PR-2, PR-5, VPEgamma, AtrbohD and AtrbohF were highly expressed when
      the mutant plants were grown under non-sterile conditions. The expression of the
      AtPDR8 gene was enhanced by infection of virulent and avirulent bacterial
      pathogens. Our results indicate that AtPDR8 is a key factor controlling the
      extent of cell death in the defense response and suggest that AtPDR8 transports
      some substance(s) which is closely related to the response of plants to
      pathogens.

PMID- 16415067
TI  - Ozone-induced expression of the Arabidopsis FAD7 gene requires salicylic acid,
      but not NPR1 and SID2.
AB  - The Arabidopsis FAD7 gene encodes a plastid omega-3 fatty acid desaturase that
      catalyzes the desaturation of dienoic fatty acids to trienoic fatty acids in
      chloroplast membrane lipids. The expression of FAD7 was rapidly and locally
      induced by ozone exposure, which causes oxidative responses equivalent to
      pathogen-induced hypersensitive responses and subsequently activates various
      defense-related genes. This induction was reduced in salicylic acid (SA)
      deficient NahG plants expressing SA hydroxylase, but was unaffected in etr1 and
      jar1 mutants, which are insensitive to ethylene and jasmonic acid (JA),
      respectively. The SA dependence of the FAD7 induction was confirmed by the
      exogenous application of SA. SA-induced expression of FAD7 in the npr1 mutant
      which is defective in an SA signaling pathway occurred to the same extent as in
      the wild type. Furthermore, in the sid2 mutant which lacks an enzyme required for
      SA biosynthesis, the expression of FAD7 was induced by ozone exposure. These
      results suggest that the ozone-induced expression of FAD7 gene requires SA, but
      not ethylene, JA, NPR1 and SID2.

PMID- 16415068
TI  - Polyamines induce rapid biosynthesis of nitric oxide (NO) in Arabidopsis thaliana
      seedlings.
AB  - In this study, we examined the regulation by putrescine, spermidine and spermine
      of nitric oxide (NO) biosynthesis in Arabidopsis thaliana seedlings. Using a
      fluorimetric method employing the cell-impermeable NO-binding dye
      diaminorhodamine-4M (DAR-4M), we observed that the polyamines (PAs) spermidine
      and spermine greatly increased NO release in the seedlings, whereas arginine and
      putrescine had little or no effect. Spermine, the most active PA, stimulated NO
      release with no apparent lag phase. The response was quenched by addition of 2
      aminoethyl-2-thiopseudourea (AET), an inhibitor of the animal nitric oxide
      synthase (NOS) and plant NO biosynthesis, and by 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-1-oxy-3-oxide (PTIO), an NO scavenger. By fluorescence
      microscopy, using the cell-permeable NO-binding dye diaminorhodamine-4M
      acetoxymethyl ester (DAR-4M AM), we observed that PAs induced NO biosynthesis in
      specific tissues in Arabidopsis seedlings. Spermine and spermidine increased NO
      biosynthesis in the elongation zone of the Arabidopsis root tip and in primary
      leaves, especially in the veins and trichomes, while in cotyledons little or no
      effect of PAs beyond the endogenous levels of NO-induced fluorescence was
      observed. We conclude that PAs induce NO biosynthesis in plants.

PMID- 16415069
TI  - Predicting prognosis in stable angina--results from the Euro heart survey of
      stable angina: prospective observational study.
AB  - OBJECTIVES: To investigate the prognosis associated with stable angina in a
      contemporary population as seen in clinical practice, to identify the key
      prognostic features, and from this to construct a simple score to assist risk
      prediction. DESIGN: Prospective observational cohort study. SETTING: Pan-European
      survey in 156 outpatient cardiology clinics. PARTICIPANTS: 3031 patients were
      included on the basis of a new clinical diagnosis by a cardiologist of stable
      angina with follow-up at one year. MAIN OUTCOME MEASURE: Death or non-fatal
      myocardial infarction. RESULTS: The rate of death and non-fatal myocardial
      infarction in the first year was 2.3 per 100 patient years; the rate was 3.9 per
      100 patient years in the subgroup (n = 994) with angiographic confirmation of
      coronary disease. The clinical and investigative factors most predictive of
      adverse outcome were comorbidity, diabetes, shorter duration of symptoms,
      increasing severity of symptoms, abnormal ventricular function, resting
      electrocardiogaphic changes, or not having any stress test done. Results of non
      invasive stress tests did not significantly predict outcome in the population who
      had tests done. A score was constructed using the parameters predictive of
      outcome to estimate the probability of death or myocardial infarction within one
      year of presentation with stable angina. CONCLUSIONS: A score based on the
      presence of simple, objective clinical and investigative variables makes it
      possible to discriminate effectively between very low risk and very high risk
      patients and to estimate the probability of death or non-fatal myocardial
      infarction over one year.

PMID- 16415070
TI  - Estrogen receptor-alpha mediates acute myocardial protection in females.
AB  - Sex differences in myocardial recovery have been reported after acute ischemia
      and reperfusion injury. Estrogen and the estrogen receptor are critical
      determinants of cardiovascular sex differences. However, the mechanistic pathways
      responsible for these differences remain unknown. We hypothesized that estrogen
      receptor-alpha is an important modulator of 1) myocardial functional recovery
      after ischemia and 2) inflammatory signaling via MAPK. To study this, adult male
      and female wild-type (WT) and estrogen receptor-alpha knockout (ER1KO) mouse
      hearts were isolated, perfused via Langendorff model, and subjected to 20 min of
      ischemia and 60 min of reperfusion. Myocardial contractile function (left
      ventricular developed pressure and positive and negative first derivative of
      pressure) was continuously recorded. After ischemia-reperfusion, hearts were
      assessed for expression of inflammatory cytokines (ELISA) and activation of MAPK
      and caspase-3 (Western blot analysis). Data were analyzed with two-way ANOVA or
      Student's t-test, and P < 0.05 was statistically significant. ER1KO females
      exhibited significantly less functional recovery than WT females and were similar
      to WT males. Activated ERK was increased in female WT hearts compared with female
      ER1KO. Activated JNK was decreased in female WT hearts compared with female
      ER1KO. No significant differences were found between male WT, female WT, male
      ER1KO, and female ER1KO in activated p38 MAPK, proinflammatory cytokine
      expression, and proapoptotic signaling. Estrogen receptor-alpha plays a role in
      the protection observed in the female heart. Differential activation of MAPK may
      mediate this protection. Further studies are necessary to delineate these
      mechanistic pathways.

PMID- 16415071
TI  - Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of
      hypertension.
AB  - Cardiac remodeling is a hallmark hypertension-induced pathophysiology. In the
      current study, the role of the angiotensin-(1-7) fragment in modulating cardiac
      remodeling was examined. Sprague-Dawley rats underwent uninephrectomy surgery and
      were implanted with a deoxycorticosterone acetate (DOCA) pellet. DOCA animals had
      their drinking water replaced with 0.9% saline solution. A subgroup of DOCA-salt
      animals was implanted with osmotic minipumps, which delivered angiotensin-(1-7)
      chronically (100 ng.kg(-1).min(-1)). Control animals underwent sham surgery and
      were maintained on normal drinking water. Blood pressure was measured weekly with
      the use of the tail-cuff method, and after 4 wk of treatment, blood pressure
      responses to graded doses of angiotensin II were determined by direct carotid
      artery cannulation. Ventricle size was measured, and cross sections of the heart
      ventricles were paraffin embedded and stained using Masson's Trichrome to measure
      interstitial and perivascular collagen deposition and myocyte diameter. DOCA-salt
      treatment caused significant increases in blood pressure, cardiac hypertrophy,
      and myocardial and perivascular fibrosis. Angiotensin-(1-7) infusion prevented
      the collagen deposition effects without any effect on blood pressure or cardiac
      hypertrophy. These results indicate that angiotensin-(1-7) selectively prevents
      cardiac fibrosis independent of blood pressure or cardiac hypertrophy in the DOCA
      salt model of hypertension.

PMID- 16415072
TI  - Caveolin-1-deficient aortic smooth muscle cells show cell autonomous
      abnormalities in proliferation, migration, and endothelin-based signal
      transduction.
AB  - We previously showed that ablation of caveolin-1 (Cav-1) gene expression in mice
      promotes neointimal hyperplasia in vivo, a phenomenon normally characterized by
      smooth muscle cell (SMC) migration and proliferation. Whether these defects are
      cell autonomous, i.e., due to loss of Cav-1 within SMCs or loss of Cav-1
      expression in other adjacent cell types in vivo, remains unknown. Cav-1 has been
      shown to associate with receptors for many vasoactive factors on the SMC surface.
      Therefore, Cav-1 might be an important regulator of SMC proliferation, migration,
      and signal transduction. To mechanistically dissect the role of Cav-1 in SMC
      signaling, we isolated SMCs from the aortas (AoSMCs) of Cav-1-deficient (Cav-1(-/
      )) mice and characterized these cells with respect to their proliferation,
      migration, and Ca(2+) response to an important vasoactive factor, endothelin-1
      (ET-1). 5-Bromo-2'-deoxyuridine incorporation and a wound-healing assay showed an
      increase in proliferation and migration rates in Cav-1(-/-) compared with wild
      type (Cav-1(+/+)) AoSMCs. Cav-1(-/-) AoSMCs demonstrated upregulation of
      phosphorylated ERK1/2, cyclin D1, and proliferating cell nuclear antigen and
      reduced expression of the cyclin-dependent kinase inhibitor p27(Kip1). The Ca(2+)
      response was examined in the presence of ET-1 and assessed by confocal microscopy
      with the Ca(2+)-sensitive fluorescent probe fluo 3. When treated with ET-1, Cav
      1(-/-) AoSMCs exhibited a faster and larger increase in free intracellular Ca(2+)
      than Cav-1(+/+) cells. The ET-1-induced response in Cav-1(-/-) cells was mediated
      by the ET(B) receptor, as shown using the ET(B) receptor antagonist BQ-788 and
      the ET(A) receptor antagonist BQ-123. In Cav-1(-/-) cells, ET(A) receptor
      expression was reduced and ET(B) receptor expression was upregulated. Therefore,
      Cav-1 ablation increased the ET-1-induced Ca(2+) response in SMCs by altering the
      type and expression level of the ET receptor (i.e., receptor isoform switching).
      These data suggest a novel regulatory role for Cav-1 in SMCs with respect to
      their proliferation, migration, and Ca(2+)-mediated signaling.

PMID- 16415073
TI  - Assessment of parasympathetic reactivation after exercise.
AB  - The objective of this study was to evaluate whether heart rate variability (HRV)
      can be used as an index of parasympathetic reactivation after exercise. Heart
      rate recovery after exercise has recently been shown to have prognostic
      significance and has been postulated to be related to abnormal recovery of
      parasympathetic tone. Ten normal subjects [5 men and 5 women; age 33 +/- 5 yr
      (mean +/- SE)] exercised to their maximum capacity, and 12 subjects (10 men and 2
      women; age 61 +/- 10 yr) with coronary artery disease exercised for 16 min on two
      separate occasions, once in the absence of atropine and once with atropine (0.04
      mg/kg) administered during exercise. The root mean square residual (RMS), which
      measures the deviation of the R-R intervals from a straight line, as well as the
      standard deviation (SD) and the root mean square successive difference of the R-R
      intervals (MSSD), were measured on successive 15-, 30-, and 60-s segments of a 5
      min ECG obtained immediately after exercise. In recovery, the R-R interval was
      shorter with atropine (P < 0.0001). Without atropine, HRV, as measured by the
      MSSD and RMS, increased early in recovery from 4.1 +/- 0.4 and 3.7 +/- 0.4 ms in
      the first 15 s to 7.2 +/- 1.0 and 7.4 +/- 0.9 ms after 1 min, respectively (P <
      0.0001). RMS (range 1.7-2.1 ms) and MSSD were less with atropine (P < 0.0001).
      RMS remained flat throughout recovery, whereas MSSD showed some decline over time
      from 3.0 to 2.2 ms (P < 0.002). RMS and MSSD were both directly related (r(2) =
      0.47 and 0.56, respectively; P < 0.0001) to parasympathetic effect, defined as
      the difference in R-R interval without and with atropine. In conclusion, RMS and
      MSSD are parameters of HRV that can be used in the postexercise recovery period
      as indexes of parasympathetic reactivation after exercise. These tools may
      improve our understanding of parasympathetic reactivation after exercise and the
      prognostic significance of heart rate recovery.

PMID- 16415075
TI  - Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals
      subtle abnormalities in myocardial perfusion and mechanics.
AB  - A decrease in the supply of ATP from the creatine kinase (CK) system is thought
      to contribute to the evolution of heart failure. However, previous studies on
      mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-))
      have not revealed overt left ventricular dysfunction. The aim of this study was
      to employ novel MRI techniques to measure maximal myocardial velocity (V(max))
      and myocardial perfusion and thus determine whether abnormalities in the
      myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after
      myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all
      CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was
      significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-),
      1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI,
      1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial
      perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/
      ), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-)
      MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a
      significantly reduced capillary density (histology). In conclusion, myocardial
      function in transgenic mice may appear normal when only gross indexes of
      performance such as EF are assessed. However, the use of a combination of novel
      MRI techniques to measure myocardial perfusion and mechanics allowed the
      abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK
      deficient mice is characterized by reduced perfusion and reduced maximal
      contraction velocity, suggesting that the myocardial hypertrophy seen in these
      mice cannot fully compensate for the absence of the CK system.

PMID- 16415074
TI  - Regulation of antisense RNA expression during cardiac MHC gene switching in
      response to pressure overload.
AB  - Hypertension has been shown to cause cardiac hypertrophy and a shift in myosin
      heavy chain (MHC) gene expression from the faster alpha- to slower beta-MHC
      isoform. The expression of the beta- and alpha-MHC pre-mRNAs, mRNAs, as well as
      the newly discovered antisense beta-RNA were analyzed in three regions of the
      normal control (NC) and 12-day pressure-overloaded (AbCon) hearts: the left
      ventricle apex, left ventricle base, and the septum. The RNA analyses in the
      AbCon heart targeted both the 5' and the 3' ends of each RNA molecule. beta-MHC
      mRNA expression significantly increased relative to control in all three regions,
      regardless of the target site (5' or 3' end). In contrast, beta-MHC pre-mRNA
      expression in the AbCon heart depended on the site of the measurement (5' vs. 3'
      end). For example, whereas the pre-mRNA did not change when targeted at the 3'
      end (last intron), it increased significantly in the AbCon heart when measurement
      targeted the 5' end (2nd intron) of the 25-kb molecule. Analyses of the antisense
      beta-RNA revealed that its expression in the AbCon heart was significantly
      decreased relative to control regardless of its measurement site. A negative
      correlation was observed between the beta-mRNA expression and the antisense beta
      RNA (P < 0.05), suggesting an inhibitory role of antisense RNA on the sense beta
      MHC gene expression. In contrast, a positive correlation was observed between the
      antisense beta-RNA and the alpha-MHC pre-mRNA (P < 0.05). This latter observation
      along with the alpha-MHC gene position relative to that of the beta-antisense
      suggest that the alpha-MHC sense and beta-antisense transcription are coregulated
      likely via common intergenic regulatory sequences. Our results suggest that the
      increased beta-MHC expression in the AbCon heart not only is the result of
      increased beta-MHC transcription but also involves an antisense beta-RNA
      regulation scheme. Although the exact mechanism concerning antisense regulation
      is not clear, it could involve modulation of both transcriptional activity of the
      beta-MHC gene and posttranscriptional processing.

PMID- 16415076
TI  - Role of adiponectin receptors in endothelin-induced cellular hypertrophy in
      cultured cardiomyocytes and their expression in infarcted heart.
AB  - Adiponectin, an adipocyte-derived protein, has cardioprotective actions. We
      elucidated the role of the adiponectin receptors AdipoR1 and AdipoR2 in the
      effects of adiponectin on endothelin-1 (ET-1)-induced hypertrophy in cultured
      cardiomyocytes, and we examined the expression of adiponectin receptors in normal
      and infarcted mouse hearts. Recombinant full-length adiponectin suppressed the ET
      1-induced increase in cell surface area and [(3)H]leucine incorporation into
      cultured cardiomyocytes compared with cells treated with ET-1 alone. Transfection
      of small interfering RNA (siRNA) specific for AdipoR1 or AdipoR2 reversed the
      suppressive effects of adiponectin on ET-1-induced cellular hypertrophy in
      cultured cardiomyocytes. Adiponectin induced phosphorylation of AMP-activated
      protein kinase (AMPK) and inhibited ET-1-induced ERK1/2 phosphorylation, which
      were also reversible by transfection of siRNA for AdipoR1 or AdipoR2 in cultured
      cardiomyocytes. Transfection of siRNA for alpha(2)-catalytic subunits of AMPK
      reduced the inhibitory effects of adiponectin on ET-1-induced cellular
      hypertrophy and ERK1/2 phosphorylation. Effects of globular adiponectin were
      similar to those of full-length adiponectin, and siRNA for AdipoR1 reversed the
      actions of globular adiponectin. Compared with normal left ventricle, expression
      levels of AdipoR1 mRNA and protein were decreased in the remote, as well as the
      infarcted, area after myocardial infarction in mouse hearts. In conclusion,
      AdipoR1 and AdipoR2 mediate the suppressive effects of full-length and globular
      adiponectin on ET-1-induced hypertrophy in cultured cardiomyocytes, and AMPK is
      involved in signal transduction through these receptors. AdipoR1 and AdipoR2
      might play a role in the pathogenesis of ET-1-related cardiomyocyte hypertrophy
      after myocardial infarction.

PMID- 16415077
TI  - Pressure-calcium relationships in perfused mouse hearts.
AB  - We explored the relationship between left ventricular (LV) pressure and
      intracellular free calcium concentration ([Ca](i)) in the isolated perfused mouse
      heart. [Ca](i) (rhod-2) and LV pressure were recorded simultaneously. In response
      to increases in LV volume (Frank-Starling, FS, protocol), there were increases in
      developed pressure (up to 250%), with no changes in pressure morphology (rise or
      relaxation time) or [Ca](i) (magnitude and morphology) for up to 10 min. During
      transient increases in the stimulus interval at a fixed LV volume (mechanical
      restitution, MR, protocol), developed pressure increased significantly (31.3 +/-
      1.2%), with relatively small changes in peak systolic [Ca](i) (7.4 +/- 1.4%). The
      relaxation of [Ca](i), however, was prolonged (30.0 +/- 5.5%), resulting in
      prolonged pressure relaxation (21.2 +/- 1.9%) and increased area under the
      calcium transient that paralleled the increase in developed pressure (1:1 ratio).
      A model-based analysis showed that changes in LV pressure during the MR protocol
      could be completely explained by altered [Ca](i); it was not necessary to invoke
      any changes in model parameters (i.e., dynamic processes that link calcium to
      pressure). For the FS data, the model predicted only a change in the gain
      parameter; however, this change alone cannot reproduce well-established length
      dependent changes in the steady-state force-pCa relationship. In summary, the
      mouse myocardium appears to be unique in that significant changes in peak
      developed pressure can occur with little or no change in the peak [Ca](i).
      Additionally, unlike other mammalian species, load-dependent prolongation of
      pressure relaxation is absent in the mouse heart, and pressure relaxation is
      primarily governed by intracellular free calcium relaxation.

PMID- 16415078
TI  - Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle.
AB  - The deficiency of dystrophin, a critical membrane stabilizing protein, in the mdx
      mouse causes an elevation in intracellular calcium in myocytes. One mechanism
      that could elicit increases in intracellular calcium is enhanced influx via the L
      type calcium channels. This study investigated the effects of the
      dihydropyridines BAY K 8644 and nifedipine and alterations in dihydropyridine
      receptors in dystrophin-deficient mdx hearts. A lower force of contraction and a
      reduced potency of extracellular calcium (P < 0.05) were evident in mdx left
      atria. The dihydropyridine agonist BAY K 8644 and antagonist nifedipine had 2.7-
      and 1.9-fold lower potencies in contracting left atria (P < 0.05). This
      corresponded with a 2.0-fold reduction in dihydropyridine receptor affinity
      evident from radioligand binding studies of mdx ventricular homogenates (P <
      0.05). Increased ventricular dihydropyridine receptor protein was evident from
      both radioligand binding studies and Western blot analysis and was accompanied by
      increased mRNA levels (P < 0.05). Patch-clamp studies in isolated ventricular
      myocytes showed no change in L-type calcium current density but revealed delayed
      channel inactivation (P < 0.05). This study indicates that a deficiency of
      dystrophin leads to changes in dihydropyridine receptors and L-type calcium
      channel properties that may contribute to enhanced calcium influx. Increased
      influx is a potential mechanism for the calcium overload observed in dystrophin
      deficient cardiac muscle.

PMID- 16415079
TI  - Heterogeneous response of microvascular endothelial cells to shear stress.
AB  - We investigated changes in calcium concentration in cultured bovine aortic
      endothelial cells (BAECs) and rat adrenomedulary endothelial cells (RAMECs,
      microvascular) in response to different levels of shear stress. In BAECs, the
      onset of shear stress elicited a transient increase in intracellular calcium
      concentration that was spatially uniform, synchronous, and dose dependent. In
      contrast, the response of RAMECs was heterogeneous in time and space. Shear
      stress induced calcium waves that originated from one or several cells and
      propagated to neighboring cells. The number and size of the responding groups of
      cells did not depend on the magnitude of shear stress or the magnitude of the
      calcium change in the responding cells. The initiation and the propagation of
      calcium waves in RAMECs were significantly suppressed under conditions in which
      either purinergic receptors were blocked by suramin or extracellular ATP was
      degraded by apyrase. Exogenously applied ATP produced similarly heterogeneous
      responses. The number of responding cells was dependent on ATP concentration, but
      the magnitude of the calcium change was not. Our data suggest that shear stress
      stimulates RAMECs to release ATP, causing the increase in intracellular calcium
      concentration via purinergic receptors in cells that are heterogeneously
      sensitive to ATP. The propagation of the calcium signal is also mediated by ATP,
      and the spatial pattern suggests a locally elevated ATP concentration in the
      vicinity of the initially responding cells.

PMID- 16415080
TI  - Hypoxia promotes relaxation of bovine coronary arteries through lowering
      cytosolic NADPH.
AB  - Hypoxia relaxes endothelium-denuded bovine coronary arteries (BCA) through
      mechanisms that do not appear to involve reactive oxygen species, prostaglandins,
      or nitric oxide. Because of similarities in the relaxation of BCA to hypoxia
      (Po(2) = 8-10 Torr) and inhibitors of the pentose phosphate pathway (PPP)
      including 6-aminonicotinamide and epiandrosterone, we measured NADPH and NADP and
      found that hypoxia caused NADPH oxidation (decreased NADPH/NADP). The relaxation
      to hypoxia was similar to previously reported properties of relaxation to PPP
      inhibitors in that both responses were associated with glutathione oxidation and
      depressed intracellular calcium release and calcium influx-mediated contractile
      responses. Inhibitors of potassium channels had minimal effects on these
      relaxation responses. Relaxation to hypoxia and PPP inhibitors were attenuated by
      a thiol reductant (3 mM dithiothreitol) and by eliciting contraction with an
      activator of protein kinase C (phorbol 12,13-dibutyrate). In the presence of
      contraction to U-46619, relaxation to hypoxia and PPP inhibitors were attenuated
      by the sarco(endo)plasmic reticulum Ca(2+)-ATPase pump inhibitor 200 microM
      cyclopiazonic acid and by 10 mM pyruvate. Hypoxia decreased BCA levels of glucose
      6-phosphate but not ATP. Pyruvate prevented the hypoxia-elicited decrease in
      glucose-6-phosphate and glutathione oxidation, and it increased NADPH levels
      under hypoxia to levels observed under normoxia. Thus hypoxia causes a metabolic
      stress on the PPP that promotes BCA relaxation through processes controlled by
      lowering the levels of cytosolic NADPH.

PMID- 16415081
TI  - Plaque-prone hemodynamics impair endothelial function in pig carotid arteries.
AB  - Hemodynamic forces play an active role in vascular pathologies, particularly in
      relation to the localization of atherosclerotic lesions. It has been established
      that low shear stress combined with cyclic reversal of flow direction
      (oscillatory shear stress) affects the endothelial cells and may lead to an
      initiation of plaque development. The aim of the study was to analyze the effect
      of hemodynamic conditions in arterial segments perfused in vitro in the absence
      of other stimuli. Left common porcine carotid segments were mounted into an ex
      vivo arterial support system and perfused for 3 days under unidirectional high
      and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) and oscillatory shear
      stress (0.3 +/- 3 dyn/cm(2)). Bradykinin-induced vasorelaxation was drastically
      decreased in arteries exposed to oscillatory shear stress compared with
      unidirectional shear stress. Impaired nitric oxide-mediated vasodilation was
      correlated to changes in both endothelial nitric oxide synthase (eNOS) gene
      expression and activation in response to bradykinin treatment. This study
      determined the flow-mediated effects on native tissue perfused with
      physiologically relevant flows and supports the hypothesis that oscillatory shear
      stress is a determinant factor in early stages of atherosclerosis. Indeed,
      oscillatory shear stress induces an endothelial dysfunction, whereas
      unidirectional shear stress preserves the function of endothelial cells.
      Endothelial dysfunction is directly mediated by a downregulation of eNOS gene
      expression and activation; consequently, a decrease of nitric oxide production
      and/or bioavailability occurs.

PMID- 16415083
TI  - Induction of mitochondrial ROS production by electrophilic lipids: a new pathway
      of redox signaling?

PMID- 16415082
TI  - Measurement of myocardial free radical production during exercise using EPR
      spectroscopy.
AB  - Exercise is associated with an increase in oxygen flux through the mitochondrial
      electron transport chain that has recently been demonstrated to increase the
      production of reactive oxygen species (ROS) in skeletal muscle. This study
      examined whether exercise also causes free radical production in the heart. We
      measured ROS production in seven chronically instrumented dogs during rest and
      treadmill exercise (6.4 km/h at 10 degrees grade; and heart rate, 204 +/- 3
      beats/min) using electron paramagnetic resonance spectroscopy in conjunction with
      the spin trap alpha-phenyl-tert-butylnitrone (PBN) (0.14 mol/l) in blood
      collected from the aorta and coronary sinus (CS). To improve signal detection,
      the free radical adducts were deoxygenated over a nitrogen stream for 15 min and
      extracted with toluene. The hyperfine splitting constants of the radicals were
      alpha(N) = 13.7 G and alpha(H) = 1.0 G, consistent with an alkoxyl or carbon
      centered radical. Resting aortic and CS PBN adduct concentrations were 6.7 and
      6.3 x 10(8) arbitrary units (P = not significant). Both aortic and CS adduct
      concentrations increased during exercise, but there was no significant difference
      between the aortic and CS concentrations. Thus, in contrast to skeletal muscle,
      submaximal treadmill exercise did not result in detectable free radical
      production by the heart.

PMID- 16415084
TI  - The use of anthropometric proportion indices in the measurement of facial
      attractiveness.
AB  - This study used anthropometric data in the form of Farkas' proportion indices in
      order to quantify facial attractiveness, and to relate measured change through
      surgery, to clinical judgement. Standardized photographs of 15 orthognathic
      patients were used in album form and rated by 10 experienced clinicians: album 1
      for facial attractiveness (before surgery) and album 2 for improvement in facial
      attractiveness (before and after surgery). Twenty-five proportion indices were
      selected and linear measurements recorded from the pre- and post-surgical
      photographs. The corresponding change in indices and in clinicians' scores were
      compared. The clinicians' assessment of the degree of improvement in facial
      appearance achieved through surgery, related closely to the scores produced by
      the change in proportion indices (r = 0.698, P = 0.004). Clinical assessment
      demonstrated a clear inverse relationship between initial attractiveness rating
      and the degree of improvement achieved through orthognathic surgery (r = -0.781,
      P = 0.001). The results showed good repeatability in terms of clinical
      assessment, photography and digitization. The method would appear to have
      potential for further development, possibly into a 'facial attractiveness index'
      for the objectives of quantification of improvement achieved through treatment.

PMID- 16415085
TI  - Influence of sex hormone disturbances on the internal structure of the mandible
      in newborn mice.
AB  - It has not yet been clarified how sex hormones affect craniofacial bone
      development immediately after birth. The purpose of this study was to examine the
      effects of sex hormone deficiency on craniofacial bone development immediately
      after birth, in terms of the internal structure of the mandible in newborn mice
      with orchiectomy (ORX) and ovariectomy (OVX). ORX, OVX and a sham-operation were
      performed on 40 five-day-old C57BL/6J mice. Eight weeks after surgery, each
      mandible was subjected to histomorphometric analysis of trabecular (Tr) and
      cortical (Ct) bone mineral density (BMD) by peripheral quantitative computed
      tomography (pQCT). In the experimental groups, a significant reduction in BMD was
      found in comparison with the control groups. In histomorphometric analysis, the
      number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the
      condyle and the thickness of the condylar cartilage layer was significantly
      greater in the experimental mice than in the controls. Trabecular bone volume of
      the condyle measured on azocarmine-aniline blue (AZAN) sections was significantly
      less in the experimental mice than in the controls. These results indicate that
      mandibular growth is inhibited by sex hormone disturbances and the relevant
      internal structures changed. The findings show that sex hormones are one of the
      key determinants of mandibular growth and development immediately after birth.

PMID- 16415086
TI  - Nickel in dental plaque and saliva in patients with and without orthodontic
      appliances.
AB  - The aim of this study was to compare the content of nickel in the saliva and
      dental biofilm in young patients with and without orthodontic appliances. The
      possible influence of a dietary intake of nickel on recorded nickel levels was
      examined. Nickel content in unstimulated whole saliva and in dental plaque of 24
      boys and girls (mean age 14.8 years) with intraoral fixed orthodontic appliances
      was compared with 24 adolescents without such an appliance. Sample collection was
      set up to exclude nickel contamination. Diet intake was recorded for the
      preceding 48 hours to account for the influence of recent nickel content in food.
      Saliva and plaque were analysed for nickel content using an electrothermal atomic
      absorption spectrometric (ETAAS) method. The acidified saliva samples were
      analysed as Millipore-filtered saliva with filter-retained fractions and plaque
      following dissolution in acids. No significant difference in nickel content of
      filtered saliva was found between the test and the control samples (P = 0.607);
      the median values of nickel content were 0.005 and 0.004 mug/g saliva,
      respectively. On the other hand, a significant difference was found for the
      filter-retained fraction (P = 0.008); median values for nickel were 25.3 and 14.9
      mug/g, respectively. A significant difference in nickel content between test and
      control samples was also found in plaque collected at various tooth sites (P =
      0.001; median values 1.03 and 0.45 mug/g, respectively). A stronger difference
      was found when comparing plaque collected from metal-covered tooth surfaces than
      from enamel surfaces of orthodontic patients. No association could be found
      between calculated dietary intake of nickel and recorded nickel in the test and
      control samples. It is concluded that nickel release occurs into the dental
      plaque and components of saliva of orthodontic patients, a situation that may
      reflect time dependence of its release from orthodontic appliances into the oral
      cavity and an aggregation of nickel at plaque sites.

PMID- 16415087
TI  - Regulation of volume-sensitive osmolyte efflux from human SH-SY5Y neuroblastoma
      cells following activation of lysophospholipid receptors.
AB  - The ability of the lysophospholipids sphingosine 1-phosphate (S1P) and
      lysophosphatidic acid (LPA) to promote the release of the organic osmolyte
      taurine in response to hypoosmotic stress has been examined. Incubation of SH
      SY5Y neuroblastoma cells under hypoosmotic conditions (230 mOsM) resulted in a
      time-dependent release of taurine that was markedly enhanced (3-7-fold) by the
      addition of micromolar concentrations of either S1P or LPA. At optimal
      concentrations, the effects of S1P and LPA on taurine efflux were additive and
      mediated via distinct receptors. Inclusion of 1,9-dideoxyfoskolin, 5-nitro-2-(3
      phenylpropylamino benzoic acid, or 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3
      dihydro-1-oxo-1H-inden-5-yl)oxy]-butanoic acid blocked the ability of both
      lysophospholipids to enhance taurine release, indicating the mediation of a
      volume-sensitive organic osmolyte and anion channel. Both S1P and LPA elicited
      robust increases in intracellular calcium concentration that were attenuated by
      the removal of extracellular calcium, abolished by the depletion of intracellular
      calcium with thapsigargin, and were independent of phosphoinositide turnover.
      Taurine efflux mediated by S1P and LPA was unaffected by the removal of
      extracellular calcium but was attenuated by depletion of intracellular calcium
      (34-38%) and by inhibition of protein kinase C (PKC) with chelerythrine (38-72%).
      When intracellular calcium was depleted and PKC was inhibited, S1P- or LPA
      stimulated taurine efflux was inhibited by 80%. Pretreatment of the cells with
      pertussis toxin, toxin B, or cytochalasin D had no effect on lysophospholipid
      stimulated taurine efflux. The results indicate that both S1P and LPA receptors
      facilitate osmolyte release via a phospholipase C-independent mechanism that
      requires the availability of intracellular calcium and PKC activity.

PMID- 16415089
TI  - Clozapine modulates aromatic L-amino acid decarboxylase activity in mouse
      striatum.
AB  - Clozapine is efficacious for treating dopaminergic psychosis in Parkinson's
      disease and ameliorates l-DOPA-induced motor complications. Based on its
      pharmacology and reported enhancing effects on dopamine metabolism and tyrosine
      hydroxylase activity, we investigated whether it could modulate the activity of
      aromatic l-amino acid decarboxylase (AAAD), the second enzyme for the
      biosynthesis of catecholamines and indoleamines. A single dose of clozapine
      increased AAAD activity of striatum in a dose- and time-dependent manner. At 1 h,
      enhanced enzyme activity was characterized by an increased V(max) for substrate
      and cofactor and was accompanied by elevated levels of protein in striatum and
      mRNA in substantia nigra, ventral tegmental area, locus coeruleus, and raphe
      nuclei. Acute clozapine increased tyrosine hydroxylase activity in striatum but
      with differing temporal patterns from AAAD and heightened dopamine metabolism.
      Interestingly, the response of the dopaminergic markers to clozapine was greater
      following a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion.
      Chronically administered clozapine increased AAAD activity and protein and
      dopamine metabolism in striatum without affecting tyrosine hydroxylase. Exogenous
      l-DOPA decarboxylation was accelerated in the striatum of intact and MPTP
      lesioned mice following acute clozapine, and the effect was exaggerated in the
      MPTP mice. To identify receptors involved, antagonists of receptors occupied by
      clozapine were employed. D4, 5-HT1(A), and 5-HT2(A), in addition to D1, D2, and
      D3, antagonists, augmented AAAD activity in striatum, whereas 5-HT2(C), 5-HT3,
      muscarinic, and alpha-1 and alpha-2 adrenergic antagonists were ineffective. For
      the first time, these studies provide evidence that clozapine modulates AAAD
      activity in the brain and suggests that dopamine and serotonin receptors are
      involved.

PMID- 16415088
TI  - The pheromone androstenol (5 alpha-androst-16-en-3 alpha-ol) is a neurosteroid
      positive modulator of GABAA receptors.
AB  - Androstenol is a steroidal compound belonging to the group of odorous 16
      androstenes, first isolated from boar testes and also found in humans.
      Androstenol has pheromone-like properties in both animals and humans, but the
      molecular targets of its pheromonal activity are unknown. Androstenol is
      structurally similar to endogenous A-ring reduced neurosteroids that act as
      positive modulators of GABA(A) receptors. Here we show that androstenol has
      neurosteroid-like activity as a GABA(A) receptor modulator. In whole-cell
      recordings from cerebellar granule cells, androstenol (but not its 3beta-epimer)
      caused a concentration-dependent enhancement of GABA-activated currents (EC(50),
      0.4 microM in cultures; 1.4 microM in slices) and prolonged the duration of
      spontaneous and miniature inhibitory postsynaptic currents. Androstenol (0.1-1
      microM) also potentiated the amplitude of GABA-activated currents in human
      embryonic kidney 293 cells transfected with recombinant alpha1beta2gamma2 and
      alpha2beta2gamma2 GABA(A) receptors and, at high concentrations (10-300 microM),
      directly activated currents in these cells. Systemic administration of
      androstenol (30-50 mg/kg) caused anxiolytic-like effects in mice in the open
      field test and elevated zero-maze and antidepressant-like effects in the forced
      swim test (5-10 mg/kg). Androstenol, but not its 3beta-epimer, conferred seizure
      protection in the 6-Hz electroshock and pentylenetetrazol models (ED(50) values,
      21.9 and 48.9 mg/kg, respectively). The various actions of androstenol in the
      whole-animal models are consistent with its activity as a GABA(A) receptor
      modulator. GABA(A) receptors could represent a target for androstenol as a
      pheromone, for which it is well suited because of high volatility and
      lipophilicity, or as a conventional hormonal neurosteroid.

PMID- 16415090
TI  - Verapamil P-glycoprotein transport across the rat blood-brain barrier:
      cyclosporine, a concentration inhibition analysis, and comparison with human
      data.
AB  - To predict the magnitude of P-glycoprotein (P-gp)-based drug interactions at the
      human blood-brain barrier (BBB), rodent studies are routinely conducted where P
      gp is chemically inhibited. For such studies to be predictive of interactions at
      the human BBB, the plasma concentration of the P-gp inhibitor must be comparable
      with that observed in the clinic. Therefore, we determined the in vivo EC(50) of
      P-gp inhibition at the rat BBB using verapamil as a model P-gp substrate and
      cyclosporine A (CsA) as the model P-gp inhibitor. Under isoflurane anesthesia,
      male Sprague-Dawley rats were administered i.v. CsA to achieve pseudo steady
      state CsA blood concentrations ranging from 0 to approximately 12 microM. Then,
      an i.v. tracer dose of [(3)H]verapamil was administered, and 20 min after
      verapamil administration, the animals were sacrificed for determination of blood,
      plasma, and brain (3)H radioactivity by scintillation counting. The percentage
      increase in the brain/blood (3)H radioactivity (relative to 0 microM CsA) was
      described by the Hill equation with E(max), 1290%; EC(50), 7.2 microM; and gamma,
      3.8. Previously, using [(11)C]verapamil, we have shown that the human brain/blood
      (11)C radioactivity was increased by 79% at 2.8 microM CsA blood concentration.
      At an equivalent CsA blood concentration, the rat brain/blood (3)H radioactivity
      was increased by a remarkably similar extent of 75%. This is the first time that
      an in vivo CsA EC(50) of P-gp inhibition at the rat BBB has been determined and
      the magnitude of such inhibition was compared between the rat and the human BBB
      at the same blood CsA concentration.

PMID- 16415091
TI  - Pharmacological and electrophysiological characterization of store-operated
      currents and capacitative Ca(2+) entry in vascular smooth muscle cells.
AB  - Capacitative Ca(2+) entry (CCE) in vascular smooth muscle cells contributes to
      vasoconstrictor and mitogenic effects of vasoactive hormones. In A7r5 rat aortic
      smooth muscle cells, measurements of cytosolic free Ca(2+) concentration
      ([Ca(2+)](i)) have demonstrated that depletion of intracellular Ca(2+) stores
      activates CCE. However, there is disagreement in published studies regarding the
      regulation of this mechanism by the vasoconstrictor hormone [Arg(8)]-vasopressin
      (AVP). We have employed electrophysiological methods to characterize the membrane
      currents activated by store depletion [store-operated current (I(SOC))]. Because
      of different recording conditions, it has not been previously determined whether
      I(SOC) corresponds to CCE measured using fura-2; nor has the channel protein
      responsible for CCE been identified. In the present study, the pharmacological
      characteristics of I(SOC), including its sensitivity to blockade by 2
      aminoethoxydiphenylborane, diethylstilbestrol, or micromolar Gd(3+), were found
      to parallel the effects of these drugs on thapsigargin- or AVP-activated CCE
      measured under identical external ionic conditions using fura-2. Thapsigargin
      stimulated I(SOC) was also measured in freshly isolated rat mesenteric artery
      smooth muscle cells (MASMC). Members of the transient receptor potential (TRP)
      family of nonselective cation channels, TRPC1, TRPC4, and TRPC6, were detected by
      reverse transcription-polymerase chain reaction and Western blot in both A7r5
      cells and MASMC. TRPC1 expression was reduced in a stable A7r5 cell line
      expressing a small interfering RNA (siRNA) or by infection of A7r5 cells with an
      adenovirus expressing a TRPC1 antisense nucleotide sequence. Thapsigargin
      stimulated I(SOC) was reduced in both the TRPC1 siRNA- and TRPC1 antisense
      expressing cells, suggesting that the TRPC1 channel contributes to the I(SOC)/CCE
      pathway.

PMID- 16415092
TI  - The role of prostaglandin E receptor-dependent signaling via cAMP in Mdr1b gene
      activation in primary rat hepatocyte cultures.
AB  - Multidrug resistance (mdr) proteins of the mdr1 type function as multispecific
      xenobiotic transporters in hepatocytes. In the liver, mdr1 overexpression occurs
      during regeneration, cirrhosis, and hepatocarcinogenesis and may contribute to
      primary chemotherapy resistance. Cultured rat hepatocytes exhibit a time
      dependent "intrinsic" increase in functional mdr1b expression, which depends on
      cyclooxygenase-catalyzed prostaglandin E(2) release. In the present study, the
      prostaglandin E (EP) receptor agonist misoprostol (1-10 microg/ml) further
      enhanced intrinsic mdr1b mRNA expression in primary rat hepatocytes. On the other
      hand, [1alpha(z),2beta,5alpha]-(+)-7-[5-[1,1'-(biphenyl)-4-yl]methoxy]-2-(4
      morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848B) (30 microM), an
      antagonist of the cAMP-coupled EP4 receptor, and the protein kinase A (PKA)
      inhibitor, N-(2-[bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H89) (10
      nM), repressed intrinsic mdr1b mRNA up-regulation, whereas the stable cAMP analog
      8-bromo-cAMP (10 microM) and the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX) (100 microM) further enhanced intrinsic mdr1b expression.
      Primary rat hepatocytes, transiently transfected with reporter gene constructs
      controlled by mdr1b 5'-gene-flanking regions [-1074 to +154 base pairs (bp) or 
      250 to +154 bp], demonstrated pronounced mdr1b promoter activity, already without
      the addition of exogenous modulators. Nevertheless, activity was further
      stimulated by misoprostol, 8-bromo-cAMP, or IBMX. Cotransfection with expression
      vectors for PKI, an inhibitor protein of cAMP-dependent PKA, or KCREB, a dominant
      negative mutant of the cAMP-responsive element-binding protein (CREB), decreased
      high-intrinsic mdr1b promoter activity. KCREB also counteracted misoprostol
      induced mdr1b promoter activation. In conclusion, these data provide evidence for
      a pivotal role of EP receptor-stimulated, cAMP-dependent activation of PKA and
      CREB or CREB-related proteins in mdr1b gene activation in primary rat
      hepatocytes. Thus, these data might offer potential new target structures for the
      reversal of primary drug resistance, for example, of liver tumors.

PMID- 16415093
TI  - Pitavastatin effect on ATP binding cassette A1-mediated lipid efflux from
      macrophages: evidence for liver X receptor (LXR)-dependent and LXR-independent
      mechanisms of activation by cAMP.
AB  - The promotion of lipid efflux from macrophages is an important ATP binding
      cassette A1 (ABCA1)-mediated antiatherosclerotic mechanism that prevents
      peripheral tissues from foam cell accumulation. Statins exert beneficial
      antiatherosclerotic effects on cardiovascular disease correlated to the
      cholesterol-lowering properties and the pleiotropic activities. In this work, we
      investigated the ability of statins to modulate ABCA1-mediated lipid efflux from
      macrophages, where the protein expression was differently induced. Pitavastatin
      (0.1-10 microM) and compactin (10 microM) reduced both cholesterol and
      phospholipid efflux up to 60% from macrophages expressing ABCA1 upon treatment
      with 8-(4-chlorophenylthio)-cyclic AMP (cpt-cAMP), and this was secondary to a
      reduction of ABCA1 mRNA and protein content. Conversely, statins did not affect
      ABCA1 activity when the protein was up-regulated by 22-hydroxycholesterol/9-cis
      retinoic acid or through cholesterol loading. Statin inhibition of lipid efflux
      induced by cpt-cAMP was reversed in the presence of mevalonate, 22
      hydroxycholesterol, and cholesterol but not geranyl geraniol. In macrophages
      obtained from liver X receptor (LXR)-deficient mice, cpt-cAMP still promoted
      cholesterol efflux, but pitavastatin did not exert any effect. The present work
      shows that statins may inhibit ABCA1-mediated lipid efflux in macrophages only
      when ABCA1 protein expression is induced by cpt-cAMP and provides evidence that
      cAMP may activate ABCA1 independently of an increase of intracellular sterol
      synthesis but through at least two pathways: one independent of LXR and one
      involving an intracellular sterol(s) acting as LXR ligand(s). In addition, the
      lack of inhibitory effect on lipid efflux in cholesterol-loaded macrophages is
      likely to exclude a potential negative pleiotropic effect by statins.

PMID- 16415094
TI  - Distance from the ostium as an independent determinant of coronary plaque
      composition in vivo: an intravascular ultrasound study based radiofrequency data
      analysis in humans.
AB  - AIMS: Relative plaque composition, more than its morphology alone, is thought to
      play a pivotal role in determining propensity to vulnerability. Thus, we
      investigated in vivo whether the distance from coronary ostium to plaque location
      independently affects plaque composition in humans. This may help explaining the
      recently reported non-uniform distribution of culprit lesions along the vessel in
      acute coronary syndromes. METHODS AND RESULTS: In 51 consecutive patients (45
      men), aged 38-76 years (mean age: 58+/-10), a non-culprit vessel was investigated
      through spectral analysis of IVUS radiofrequency data (IVUS-Virtual Histology).
      The study vessel was the left anterior descending artery in 23 (45%) patients;
      the circumflex artery in nine (18%), and right coronary artery in 19 (37%). The
      overall length of the region of interest, subsequently divided into 10 mm
      segments, was 41.5+/-13 mm long (range: 30.2-78.4). No significant change was
      observed in terms of relative plaque composition along the vessel with respect to
      fibrous, fibrolipidic, and calcified tissue, whereas the percentage of lipid core
      resulted to be increased in the first (median: 8.75%; IQR: 5.7-18) vs. the third
      (median: 6.1%; IQR: 3.2-12) (P=0.036) and fourth (median: 4.5%; IQR: 2.4-7.9)
      (P=0.006) segment. At multivariable regression analysis, distance from the ostium
      resulted to be an independent predictor of relative lipid content [beta=-0.28
      (95%CI: -0.15, -0.41)], together with older age, unstable presentation, no use of
      statin, and presence of diabetes mellitus. CONCLUSION: Plaque distance from the
      coronary ostium, as an independent determinant of relative lipid content, is
      potentially associated to plaque vulnerability in humans.

PMID- 16415095
TI  - Effects of metoprolol therapy on cardiac troponin-I levels after elective
      percutaneous coronary interventions.
AB  - AIMS: Beta-blockers (BBs) have been shown to improve survival and reduce the risk
      of re-infarction in patients following myocardial infarction. There are
      conflicting data about the effects of BB therapy on cardiac biomarkers after
      percutaneous coronary interventions (PCIs). The aim of the study was to
      investigate the effects of BB use on cardiac troponin-I (cTnI) levels in patients
      who had undergone elective PCI. METHODS AND RESULTS: In this prospective study,
      287 patients with coronary artery disease were included. Patients were randomized
      either to BB or control groups prior to the intervention. Blood samples for cTnI
      were obtained before and at 6, 24, and 36 h after the procedure. Of the 287
      patients included, 143 received metoprolol succinate 100 mg/day, and 144 received
      no BB and served as the control group. Baseline clinical characteristics of both
      groups, except for history of coronary artery bypass graft surgery, were similar.
      We observed no significant difference in the elevation of cTnI levels between the
      two groups after PCI (BB group, 17 patients, 11.9%; control group, 10 patients,
      6.9%; P=0.2). CONCLUSION: Metoprolol succinate therapy seems to have no
      cardioprotective effect in limiting troponin-I rise after PCI.

PMID- 16415096
TI  - Pasteurella multocida toxin (PMT) activates RhoGTPases, induces actin
      polymerization and inhibits migration of human dendritic cells, but does not
      influence macropinocytosis.
AB  - Dendritic cells (DCs) are considered as one of the principal initiators of immune
      responses. In their immature state, they migrate into peripheral tissue in order
      to uptake antigen and to patrol for danger signals. Upon maturation, they acquire
      the ability to migrate to the lymph nodes and present the captured antigens to T
      cells in order to direct the development of specific immune responses. There is
      evidence that microbial compounds interfere with proper functions of DCs in order
      to block innate and specific immunity. Here we characterized the influence of
      Pasteurella multocida toxin (PMT) on monocyte-derived DCs. Using pull-down assays
      with recombinant rhotekin or p21-activated kinase, we demonstrated the activation
      of RhoGTPases by PMT in DCs. Moreover, PMT induced changes in DC morphology and
      actin polymerization, impaired chemotaxin-induced actin re-organization and
      inhibited their migration response. However, macropinocytosis was not influenced
      by PMT. In summary, these data indicate that PMT inhibits proper function of the
      motility machinery in DCs, which might limit the development of adaptive immune
      surveillance during infection with Pasteurella multocida.

PMID- 16415097
TI  - Prophylactic fenbendazole therapy does not affect the incidence and onset of type
      1 diabetes in non-obese diabetic mice.
AB  - Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic
      drug used to treat and limit rodent pinworm infections. However, the effect of
      its prophylactic use on the immune response of rodents is largely undefined. The
      non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes
      (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus,
      in the presence of contamination, prophylactic treatment with anthelmintics must
      be considered to maintain experimental research. Herein, we investigated the
      prophylactic use of FBZ in NOD mice to determine its effect on the incidence and
      onset of diabetes, lymphocyte sub-populations and T cell proliferative responses.
      NOD mice were separated into control and treatment groups. The treatment group
      received a diet containing FBZ. Animals were monitored for the incidence and
      onset of T1D. At matched time points, diabetic and non-diabetic mice were killed
      and splenic lymphocytes analyzed for various cell sub-populations and mitogen
      induced proliferative responses using flow cytometry. Treated and control mice
      were monitored >23 weeks with no detectable effects on the incidence or onset of
      diabetes. Moreover, no significant differences were detected in lymphocyte sub
      populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between
      control and treatment groups. These results suggest that prophylactic FBZ
      treatment does not significantly alter the incidence or onset of diabetes in NOD
      mice. The prophylactic use of FBZ, therefore, presents a viable approach for the
      prevention of pinworm infection in precious experimental animals with substantial
      scientific and economic benefits.

PMID- 16415098
TI  - Purification of splenic dendritic cells induces maturation and capacity to
      stimulate Th1 response in vivo.
AB  - Dendritic cell (DC) maturation state is a key parameter for the issue of DC-T
      cell cognate interaction, which determines the outcome of T cell activation.
      Indeed, immature DCs induce tolerance while fully mature DCs generate immunity.
      Here we show that, in the absence of any deliberate activation signal, DCs
      freshly isolated from mouse spleen spontaneously produce IL-12 and tumor necrosis
      factor-alpha and up-regulate co-stimulation molecules, even when directly re
      injected into their natural environment. Furthermore, after their isolation,
      these cells acquire the capacity to induce specific T(h)1 responses in vivo.
      These results demonstrate that the sole isolation of spleen DCs leads to the full
      maturation of these cells, which therefore cannot be considered as immature DCs.
      Moreover, we also show that the kinetics of DC activation do not influence the
      polarization of T(h) response in vivo challenging the idea that exhausted DCs
      induce preferentially T(h)2 response. Altogether, these observations should be
      taken into account in all experiments based on the transfer of ex vivo purified
      DCs.

PMID- 16415099
TI  - The proliferative response of CD4 T cells to steady-state CD8+ dendritic cells is
      restricted by post-activation death.
AB  - CD8(+) splenic dendritic cells (DCs) from steady-state mice are less effective
      than the CD8(-) DC subset in their capacity to stimulate CD4 T cell proliferation
      in culture. However, we found that the two DC subtypes were equally potent at
      activating CD4 T cells, based on up-regulation of CD69 and CD25 expression. Also,
      we found no difference in the rate of T cell death prior to entry into the first
      division. We then tracked carboxyfluorescein diacetate succinimidyl ester-labeled
      T cells and employed a quantitative model to assess in detail the CD4 T cell
      expansion process in response to stimulation with CD8(+) or with CD8(-) DCs. The
      time required for most T cells to replicate their DNA prior to the first division
      was similar in both DC cultures. However, progression of the CD4 T cell
      population through subsequent divisions was reduced in CD8(+) DCs compared with
      CD8(-) DC culture. This was associated with an increased loss of viable T cells
      at each division. Post-activation, division-associated T cell death is therefore
      a major factor in the reduced response of CD4 T cells to CD8(+) DCs.

PMID- 16415100
TI  - An indispensable role of type-1 IFNs for inducing CTL-mediated complete
      eradication of established tumor tissue by CpG-liposome co-encapsulated with
      model tumor antigen.
AB  - We have evaluated the capacity of a novel, nanoparticle-based tumor vaccine to
      eradicate established tumors in mice. C57BL/6 mice were intradermally (i.d.)
      inoculated with ovalbumin (OVA)-expressing EG-7 tumor cells. When the tumor size
      reached 7-8 mm, the tumor-bearing mice were i.d. injected near the tumor-draining
      lymph node (DLN) with liposomes encapsulated with unmethylated cytosine
      phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) (CpG
      liposomes) co-encapsulated with OVA. This vaccination protocol markedly prevented
      the growth of the established tumor mass and approximately 50% of tumor-bearing
      mice became completely cured. Tumor eradication correlated with the generation of
      OVA/H-2K(b)-tetramer(+) CTLs in the tumor DLN and at the tumor site with specific
      cytotoxicity toward EG-7 cells. Interestingly, tetramer(+) CTLs failed to be
      induced in lymph node-deficient Aly/Aly mice. Thus, tetramer(+) CTLs appeared to
      be generated in the tumor DLN and subsequently migrated into the tumor site. In
      vivo antibody blocking experiments revealed that CD8(+) T cells, but not CD4(+)
      T, NK or NKT cells, were the major effector cells mediating tumor eradication.
      CTL induction was also inhibited when vaccinated tumor-bearing mice were treated
      with both anti-IFN-alpha and anti-IFN-beta mAbs but not with anti-IFN-alpha or
      anti-IFN-beta mAb alone. Neither IFN-gamma(-/-) nor IL-12(-/-) mice showed
      impaired induction of tetramer(+) CTLs. Thus, these findings revealed that CpG
      ODN-induced IFN-alpha/beta, but not IL-12 or IFN-gamma, is critical for the
      generation of tumor-specific CTLs in response to vaccination. These results
      highlight the potential utility of CpG-liposomes co-encapsulated with protein
      tumor antigens as therapeutic vaccines in cancer patients.

PMID- 16415101
TI  - The MHC class I-related FcRn ameliorates murine Lyme arthritis.
AB  - The identification of the neonatal FcR (FcRn) as an IgG homeostasis regulator has
      led to research aimed at delineating a role for FcRn in humorally mediated
      disease. FcRn is a class I-related molecule that prolongs the half-life of serum
      IgG by preferentially binding IgG at low pH and inhibiting its degradation. Its
      role in protective immunity to infectious organisms is unknown. We investigated
      the function of FcRn in the murine model of Lyme arthritis, caused by infection
      with Borrelia burgdorferi. We infected FcRn(-/-) and wild-type mice with B.
      burgdorferi and monitored the development of arthritis. Infected FcRn(-/-) mice
      demonstrated decreased serum levels of anti-B. burgdorferi antibodies and
      borreliacidal activity. Moreover, these mutant mice developed increased ankle
      swelling and joint histopathology following infection. Our data suggest that FcRn
      ameliorates murine Lyme arthritis by preventing the degradation of protective
      borreliacidal antibodies.

PMID- 16415102
TI  - Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist
      system is responsible for the development of experimental autoimmune
      encephalomyelitis.
AB  - IL-1 is a pro-inflammatory cytokine that plays an important role in inflammation
      and host responses to infection. We have previously shown that imbalances in the
      IL-1 and IL-1R antagonist (IL-1Ra) system cause the development of inflammatory
      diseases. To explore the role of the IL-1/IL-1Ra system in autoimmune disease, we
      analyzed myelin oligodendrocyte glycoprotein (MOG)-induced experimental
      autoimmune encephalomyelitis (EAE) in mice bearing targeted disruptions of the IL
      1alpha, IL-1beta, IL-1alpha and IL-1beta (IL-1) or IL-1Ra genes. IL-1alpha/beta
      double-deficient (IL-1-/-) mice exhibited significant resistance to EAE induction
      with a significant reduction in disease severity, while IL-1alpha-/- or IL-1beta
      /- mice developed EAE in a manner similar to wild-type mice. IL-1Ra-/- mice also
      developed MOG-induced EAE normally with pertussis toxin (PTx) administration. In
      contrast to wild-type mice, however, these mice were highly susceptible to EAE
      induction in the absence of PTx administration. We found that both IFN-gamma and
      IL-17 production and proliferation were reduced in IL-1-/- T cells upon
      stimulation with MOG, while IFN-gamma, IL-17 and tumor necrosis factor-alpha
      production and proliferation were enhanced in IL-1Ra-/- T cells. These
      observations suggest that the IL-1/IL-1Ra system is crucial for auto-antigen
      specific T cell induction and contributes to the development of EAE.

PMID- 16415103
TI  - Role of T-cell-associated lymphocyte function-associated antigen-1 in the
      pathogenesis of experimental colitis.
AB  - The beta2 integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18)
      is important for lymphocyte trafficking and activation as well as recruitment to
      sites of tissue inflammation. The objective of this study was to assess the role
      of 'T-cell-associated' LFA-1 in the pathogenesis of chronic colitis in vivo.
      Transfer of CD4+CD25- T cells isolated from wild-type (wt) mice into
      immunodeficient recipients [recombinase-activating gene-1-deficient (RAG-1-/-]
      produced moderate to severe colitis, whereas RAG-1-/- mice injected with CD11a
      deficient (CD11a-/-; LFA-1-/-) donor T cells displayed minimal macroscopic and
      histological evidence of colitis. Surface expression of L-selectin, alpha4,
      alpha4beta7 and chemokine receptor-7 were similar for wt and CD11a-/- donor T
      cells. Attenuated disease in the CD11a-/- --> RAG-1-/- animals was associated
      with decreased numbers of CD4+ T cells in the mesenteric lymph nodes (MLNs),
      spleen and intestinal lamina propria (LP). In addition, significant reductions in
      Th1 cytokines were observed following ex vivo stimulation of mononuclear cells
      obtained from the MLNs and colonic LP. Interestingly, mononuclear cells obtained
      from the spleens of CD11a-/- --> RAG-1-/- exhibited enhanced pro-inflammatory
      cytokine production compared with splenocytes obtained from wt --> RAG-1-/-
      colitic mice. Taken together, our data suggest that T-cell-associated CD11a (LFA
      1) expression plays a dual role in the initiation of chronic gut inflammation by
      facilitating naive T-cell priming/activation and expansion within MLNs and by
      augmenting pro-inflammatory cytokine production following secondary stimulation
      by antigen-presenting cells in the colonic interstitium.

PMID- 16415104
TI  - B cell proliferation following CD40 stimulation results in the expression and
      activation of Src protein tyrosine kinase.
AB  - Resting normal human B cells express negligible c-src mRNA or Src protein
      tyrosine kinase; however, upon induction of proliferation, these cells express
      high levels of both mRNA and protein and show a concomitant increase in tyrosine
      kinase activity of immunoprecipitated Src. Src expression was most pronounced
      upon stimulation with CD154, and to a lesser extent CD70, Staphylococcus aureus,
      Cowan strain I and phorbol ester, and correlated with the activation of the
      cells. Transfection of cDNA for human wild-type or kinase-dead Src into Raji B
      cells resulted in an increase and decrease, respectively, of the cell numbers in
      culture, showing a direct correlation of proliferation to the expression of Src
      that was corroborated using anti-sense oligodeoxynucleotides and chemical
      inhibitors. Furthermore, the human B cell lines, Namalwa, Daudi and Raji express
      low levels of Src but express very high levels of Src after stimulation with
      CD154 that showed a correlation with increased activation. This is the first
      report of Src detectable in normal B cells. The finding that Src expression is
      inducible and correlates with stimulation by CD154 and the proliferation of the B
      cells suggests that Src may play a specific role in normal and transformed B cell
      activation/proliferation pathways mediated primarily through CD40 stimulation.

PMID- 16415105
TI  - Mycobacterium tuberculosis in the adjuvant modulates the balance of Th immune
      response to self-antigen of the CNS without influencing a "core" repertoire of
      specific T cells.
AB  - In the present study, we use modified CDR3 beta-chain spectratyping (immunoscope)
      to dissect the effect of Mycobacterium tuberculosis (MT)-derived proteins on
      individual PLP139-151-specific cells in the SJL mouse strain. In this model, the
      immunoscope technique allows the characterization of a public TCR that involves
      rearrangement of Vbeta10 and Jbeta1.1 and a semi-private TCR characterized by
      rearrangement of Vbeta4 and Jbeta1.6. Both rearrangements are specific for PLP139
      151 and sequences of the CDR3 region of the two beta-chains show a conserved
      motif for the public rearrangement and related but more variable sequences for
      the semi-private rearrangement. MT-derived proteins promote increase of IFN-gamma
      secreting cells. However, we observe that the presence and amount of MT used
      during immunization have no effect on the frequency of usage, polarization and in
      vivo expansion of cells carrying the studied rearrangements. Rather, the strong
      Th1-promoting effect of adjuvant is possibly due to recruitment toward Th1 of a
      wider spectrum of TCR repertoires. Therefore, instead of having a comprehensive
      effect on the entire repertoire, MT modulates the immune response by affecting a
      subset of antigen-specific T cells whose polarization can be adapted to the
      environment. This step establishes the final balance between Th1 and Th2 and may
      be essential for the enhancement or protection of disease.

PMID- 16415106
TI  - Transfer of regulatory T cells generated ex vivo modifies graft rejection through
      induction of tolerogenic CD4+CD25+ cells in the recipient.
AB  - Certain CD4+CD25+ T cells can induce and maintain T-cell non-responsiveness to
      donor alloantigens and have therapeutic potential in solid organ transplantation.
      Peripheral CD4+CD25- cells alloactivated with IL-2 and transforming growth factor
      beta (TGF-beta) ex vivo express the transcription factor FoxP3, and become potent
      antigen-specific CD4+CD25- suppressor cells. Here we report that the transfer of
      TGF-beta-induced regulatory CD4+ and CD8+ T cells (Tregs) co-incident with
      transplantation of a histoincompatible heart resulted in extended allograft
      survival. To account for this result, we injected non-transplanted mice with a
      single dose of CD4+ and CD8+ Tregs and transferred donor cells every 2 weeks to
      mimic the continuous stimulation of a transplant. We observed increased splenic
      CD4+CD25+ cells that were of recipient origin. These cells rendered the animals
      non-responsive to donor alloantigens by an antigen-specific and cytokine
      dependent mechanism of action. Both the increased number of CD4+CD25+ cells and
      their tolerogenic effect were dependent on continued donor antigen boosting.
      Thus, Tregs generated ex vivo can act like a vaccine that generates host
      suppressor cells with the potential to protect MHC-mismatched organ grafts from
      rejection.

PMID- 16415107
TI  - S-glutathiolation by peroxynitrite of p21ras at cysteine-118 mediates its direct
      activation and downstream signaling in endothelial cells.
AB  - The highly reactive species, peroxynitrite, is produced in endothelial cells in
      pathological states in which the production of superoxide anion and NO is
      increased. Here, we show that peroxynitrite added exogenously or generated
      endogenously in response to exposure to an NO donor or oxidized low-density
      lipoproteins (oxLDL) increases p21ras activity in bovine aortic endothelial
      cells. The activation is not dependent on upstream elements but rather is due to
      direct targeting of p21ras by reversible S-glutathiolation of cysteine thiols as
      demonstrated by biotin-labeling techniques. The time course of p21ras S
      glutathiolation following peroxynitrite corresponds to the increase in its Raf-1
      binding activity and translocation to the membrane. Moreover, p21ras S
      glutathiolation and activation can be reversed by dithiothreitol, confirming the
      importance of a disulfide bond. S-glutathiolation also promoted guanine
      nucleotide exchange of recombinant p21ras. In addition, the oxidant-induced
      activation of Mek/Erk and PI3 kinase/Akt was abrogated by dominant-negative and
      Cys-118 p21ras mutants, and the latter also prevented S-glutathiolation of
      p21ras. These results indicate that peroxynitrite arising from NO donors or
      pathological stimuli such as oxLDL triggers direct S-glutathiolation of p21ras
      Cys-118, which increases p21ras activity and mediates downstream signaling.

PMID- 16415108
TI  - Cytochrome P450 epoxygenases provide a novel mechanism for penile erection.
AB  - Erectile dysfunction (ED) is estimated to affect more than 30 million American
      men and 152 million men worldwide. Therapeutic agents targeting the nitric
      oxide/cyclic GMP signaling pathway have successfully treated patients with ED;
      however, the efficacies of these treatments are significantly lower in specific
      populations such as patients with diabetes. The goal of this study was to
      discover and identify new endothelium-derived relaxing factors involved in the
      regulation of erectile function, providing alternative therapeutic targets for
      treatment of ED. Immunoblotting results showed that protein expressions of
      epoxygenases from cytochrome P450 (CYP)2B, 2C and 2J subfamilies, as well as
      NADPH CYP reductase were present in rat corpora cavernosa, which was confirmed by
      immunohistochemical analysis. Furthermore, CYP2C was localized in cavernosal
      endothelial cells using double immunolabeling. CYP epoxygenase activity was
      analyzed by reverse-phase high-pressure liquid chromatography; and the results
      showed that 11,12- epoxyeicosatrienoic acid (EET) was the major product
      metabolized by CYP epoxygenases in rat corpora cavernosa. Inhibition of EETs
      function by injection of an EETs antagonist into rat penis significantly
      decreased intracavernosal pressure-induced by electrical stimulation of the major
      pelvic ganglion in vivo. In conclusion, our results suggest that EETs, produced
      by CYP epoxygenases, in penile endothelial cells serve as vasodilators.
      Inhibition of this pathway attenuated erectile function, suggesting that EETs are
      required for normal erection.

PMID- 16415110
TI  - Stereochemical aspects of itraconazole metabolism in vitro and in vivo.
AB  - Itraconazole (ITZ) has three chiral centers and is administered clinically as a
      mixture of four stereoisomers. This study evaluated stereoselectivity in ITZ
      metabolism. In vitro experiments were carried out using heterologously expressed
      CYP3A4. Only (2R,4S,2'R)-ITZ and (2R,4S,2'S)-ITZ were metabolized by CYP3A4 to
      hydroxy-ITZ, keto-ITZ, and N-desalkyl-ITZ. When (2S,4R,2'R)-ITZ or (2S,4R,2'S)
      ITZ was incubated with CYP3A4, neither metabolites nor substrate depletion were
      detected. Despite these differences in metabolism, all four ITZ stereoisomers
      induced a type II binding spectrum with CYP3A4, characteristic of coordination of
      the triazole nitrogen to the heme iron (K(s) 2.2-10.6 nM). All four stereoisomers
      of ITZ inhibited the CYP3A4-catalyzed hydroxylation of midazolam with high
      affinity (IC(50) 3.7-14.8 nM). Stereochemical aspects of ITZ pharmacokinetics
      were evaluated in six healthy volunteers after single and multiple oral doses. In
      vivo, after a single dose, ITZ disposition was stereoselective, with a 3-fold
      difference in C(max) and a 9-fold difference in C(min) between the (2R,4S)-ITZ
      and the (2S,4R)-ITZ pairs of diastereomers, with the latter reaching higher
      concentrations. Secondary and tertiary ITZ metabolites (keto-ITZ and N-desalkyl
      ITZ) detected in plasma were of the (2R,4S) stereochemistry. After multiple doses
      of ITZ, the difference in C(max) and C(min) decreased to 1.5- and 3.8-fold,
      respectively. The initial difference between the stereoisomeric pairs was most
      likely due to stereoselective metabolism by CYP3A4, including stereoselective
      first-pass metabolism as well as stereoselective elimination. However,
      stereoselective elimination was diminished after multiple dosing, presumably as a
      result of CYP3A4 autoinhibition. In conclusion, the metabolism of ITZ is highly
      stereoselective in vitro and in vivo.

PMID- 16415111
TI  - CYP2D6*36 gene arrangements within the cyp2d6 locus: association of CYP2D6*36
      with poor metabolizer status.
AB  - Unexplained cases of CYP2D6 genotype/phenotype discordance continue to be
      discovered. In previous studies, several African Americans with a poor
      metabolizer phenotype carried the reduced function CYP2D6*10 allele in
      combination with a nonfunctional allele. We pursued the possibility that these
      alleles harbor either a known sequence variation (i.e., CYP2D6*36 carrying a gene
      conversion in exon 9 along the CYP2D6*10-defining 100C>T single-nucleotide
      polymorphism) or novel sequences variation(s). Discordant cases were evaluated by
      long-range polymerase chain reaction (PCR) to test for gene rearrangement events,
      and a 6.6-kilobase pair PCR product encompassing the CYP2D6 gene was cloned and
      entirely sequenced. Thereafter, allele frequencies were determined in different
      study populations comprising whites, African Americans, and Asians. Analyses
      covering the CYP2D7 to 2D6 gene region established that CYP2D6*36 did not only
      exist as a gene duplication (CYP2D6*36x2) or in tandem with *10 (CYP2D6*36+*10),
      as previously reported, but also by itself. This "single" CYP2D6*36 allele was
      found in nine African Americans and one Asian, but was absent in the whites
      tested. Ultimately, the presence of CYP2D6*36 resolved genotype/phenotype
      discordance in three cases. We also discovered an exon 9 conversion-positive
      CYP2D6*4 gene in a duplication arrangement (CYP2D6*4Nx2) and a CYP2D6*4 allele
      lacking 100C>T (CYP2D6*4M) in two white subjects. The discovery of an allele that
      carries only one CYP2D6*36 gene copy provides unequivocal evidence that both
      CYP2D6*36 and *36x2 are associated with a poor metabolizer phenotype. Given a
      combined frequency of between 0.5 and 3% in African Americans and Asians,
      genotyping for CYP2D6*36 should improve the accuracy of genotype-based phenotype
      prediction in these populations.

PMID- 16415109
TI  - Callipyge mutation affects gene expression in cis: a potential role for chromatin
      structure.
AB  - Muscular hypertrophy in callipyge sheep results from a single nucleotide
      substitution located in the genomic interval between the imprinted Delta,
      Drosophila, Homolog-like 1 (DLK1) and Maternally Expressed Gene 3 (MEG3). The
      mechanism linking the mutation to muscle hypertrophy is unclear but involves DLK1
      overexpression. The mutation is contained within CLPG1 transcripts produced from
      this region. Herein we show that CLPG1 is expressed prenatally in the hypertrophy
      responsive longissimus dorsi muscle by all four possible genotypes, but postnatal
      expression is restricted to sheep carrying the mutation. Surprisingly, the
      mutation results in nonimprinted monoallelic transcription of CLPG1 from only the
      mutated allele in adult sheep, whereas it is expressed biallelically during
      prenatal development. We further demonstrate that local CpG methylation is
      altered by the presence of the mutation in longissimus dorsi of postnatal sheep.
      For 10 CpG sites flanking the mutation, methylation is similar prenatally across
      genotypes, but doubles postnatally in normal sheep. This normal postnatal
      increase in methylation is significantly repressed in sheep carrying one copy of
      the mutation, and repressed even further in sheep with two mutant alleles. The
      attenuation in methylation status in the callipyge sheep correlates with the
      onset of the phenotype, continued CLPG1 transcription, and high-level expression
      of DLK1. In contrast, normal sheep exhibit hypermethylation of this locus after
      birth and CLPG1 silencing, which coincides with DLK1 transcriptional repression.
      These data are consistent with the notion that the callipyge mutation inhibits
      perinatal nucleation of regional chromatin condensation resulting in continued
      elevated transcription of prenatal DLK1 levels in adult callipyge sheep. We
      propose a model incorporating these results that can also account for the
      enigmatic normal phenotype of homozygous mutant sheep.

PMID- 16415112
TI  - Inhibitory effects of fruit juices on CYP3A activity.
AB  - There have been very limited reports on the effects of commercial fruit juices on
      human CYP3A activity. Therefore, the inhibitory effects of readily available
      commercial fruit juices on midazolam 1'-hydroxylase activity, a marker of CYP3A,
      were evaluated in pooled human liver microsomes. The fruit juices investigated
      were black raspberry, black mulberry, plum, and wild grape. White grapefruit,
      pomegranate, and orange juice were used as positive and negative controls. The
      black mulberry juice showed the most potent inhibition of CYP3A except for
      grapefruit juice. The inhibition depended on the amount of a fruit juice added to
      the incubation mixture. The inhibitory potential of human CYP3A was in the order:
      grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The
      IC(50) values of all fruit juices tested were reduced after preincubation with
      microsomes in the presence of the NADPH-generating system, suggesting that a
      mechanism-based inhibitory component was present in these fruit juices, as in the
      case of grapefruit. The results suggest that, like grapefruit juice, commercial
      fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1'
      hydroxylation. Therefore, in vivo studies investigating the interactions between
      fruit juices such as black mulberry and wild grape and CYP3A substrates are
      necessary to determine whether inhibition of CYP3A activity by fruit juices is
      clinically relevant.

PMID- 16415113
TI  - Mutational analysis of polar amino acid residues within predicted transmembrane
      helices 10 and 16 of multidrug resistance protein 1 (ABCC1): effect on substrate
      specificity.
AB  - Human multidrug resistance protein 1 (MRP1) has a total of 17 transmembrane (TM)
      helices arranged in three membrane-spanning domains, MSD0, MSD1, and MSD2, with a
      5 + 6 + 6 TM configuration. Photolabeling studies indicate that TMs 10 and 11 in
      MSD1 and 16 and 17 in MSD2 contribute to the substrate binding pocket of the
      protein. Previous mutational analyses of charged and polar amino acids in
      predicted TM helices 11, 16, and 17 support this suggestion. Mutation of Trp(553)
      in TM10 also affects substrate specificity. To extend this analysis, we mutated
      six additional polar residues within TM10 and the remaining uncharacterized polar
      residue in TM16, Asn(1208). Although mutation of Asn(1208) was without effect,
      two of six mutations in TM10, T550A and T556A, modulated the drug resistance
      profile of MRP1 without affecting transport of leukotriene C4, 17beta-estradiol
      17-(beta-d-glucuronide) (E(2)17betaG), and glutathione. Mutation T550A increased
      vincristine resistance but decreased doxorubicin resistance, whereas mutation
      T556A decreased resistance to etoposide (VP-16) and doxorubicin. Although
      conservative mutation of Tyr(568) in TM10 to Phe or Trp had no apparent effect on
      substrate specificity, substitution with Ala decreased the affinity of MRP1 for
      E(2)17betaG without affecting drug resistance or the transport of other
      substrates tested. These analyses confirm that several amino acids in TM10
      selectively alter the substrate specificity of MRP1, suggesting that they
      interact directly with certain substrates. The location of these and other
      functionally important residues in TM helices 11, 16, and 17 is discussed in the
      context of an energy-minimized model of the membrane-spanning domains of MRP1.

PMID- 16415114
TI  - In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism.
AB  - A metabolic interaction between stiripentol (STP), an anticonvulsant agent that
      inhibits the activity of several cytochromes P450 (P450s), and clobazam (CLB), a
      1,5-benzodiazepine, used in association with STP in severe myoclonic epilepsy in
      infancy was observed in vivo. This interaction was characterized in vitro using
      cDNA-expressed CYP3A4 and CYP2C19 (main P450 involved in CLB metabolism) to
      calculate K(i) and IC(50) of stiripentol in comparison with ketoconazole (CYP3A4
      inhibitor) and omeprazole (CYP2C19 inhibitor). STP inhibited N-demethylation of
      CLB to N-desmethylclobazam (NCLB) mediated by CYP3A4 (noncompetitively) and
      CYP2C19 (competitively) with K(i) = 1.59 +/- 0.07 and 0.516 +/- 0.065 microM and
      IC(50) = 1.58 microM [95% confidence interval (CI95%) = 1.20-2.08] and 3.29
      microM (CI95% = 1.87-5.79), respectively. STP inhibited also more strongly the 4'
      hydroxylation of NCLB to 4'-hydroxy-N-desmethylclobazam by CYP2C19 [competitive
      interaction with K(i) = 0.139 +/- 0.025 microM and IC(50) = 0.276 microM (CI95% =
      0.206-0.371)]. The inhibitory effect of STP on CLB demethylation by CYP3A4 was
      much weaker than that of ketoconazole [IC(50) = 0.023 microM (CI95% = 0.016
      0.033)], whereas its effect on NCLB hydroxylation by CYP2C19 was much higher than
      that of omeprazole [IC(50) = 2.99 microM (CI95% = 2.11-4.24)]. The major in vitro
      inhibitory effect of STP on CLB metabolism and mostly on NCLB biotransformation
      is consistent with the changes in vivo in CLB and NCLB plasma concentrations in
      children treated by the association CLB/STP.

PMID- 16415115
TI  - Effect of chronic renal insufficiency on hepatic and renal udp
      glucuronyltransferases in rats.
AB  - Significant evidence exists regarding altered CYP450 enzymes in chronic renal
      insufficiency (CRI), although none exists for the phase II enzymes. The objective
      of this study was to investigate the effect of CRI on hepatic and renal UDP
      glucuronyltransferase (UGT) enzymes. Three groups of rats were included: CRI
      induced by the 5/6th nephrectomy model, control, and control pair-fed (CPF) rats.
      UGT activities were determined in liver and kidney microsomes by the 3- and 17
      glucuronidation of beta-estradiol (E2-3G and E2-17G), glucuronidation of 4
      methylumbelliferone (4-MUG), and 3-glucuronidation of morphine (M3G). UGT
      isoforms responsible for these catalytic activities were screened using
      recombinant rat UGT1A1, UGT1A2, UGT1A3, UGT1A7, UGT2B2, UGT2B3, and UGT2B8. UGT
      protein levels were examined by Western blot analysis using polyclonal
      antibodies. There was no significant difference between CRI and CPF rats in
      hepatic and/or renal E2-3G (UGT1A1), E2-17G (UGT2B3), 4-MUG (UGT1A6), and M3G
      (UGT2B1) formation. Formation of E2-17G and 4-MUG in the liver and E2-3G and 4
      MUG in the kidney was significantly reduced (p < 0.05) in CPF and CRI rats
      compared with control rats. The down-regulated glucuronidation activities were
      accompanied by corresponding reductions in protein content of specific UGT
      isoforms. These results suggest that CRI does not seem to influence the protein
      levels or catalytic activity of most of the major hepatic or renal UGT enzymes.
      The observed down-regulation of hepatic and renal UGTs in CRI and CPF rats could
      be caused by restricted food intake in these groups of rats.

PMID- 16415116
TI  - Metabolism of the A(1)1 adenosine receptor positron emission tomography ligand
      [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([18F]CPFPX) in rodents
      and humans.
AB  - Studies of plasma from mice, rats, and human volunteers evaluated methods for the
      extraction and quantification of the positron emission tomography ligand [(18)F]8
      cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([(18)F]CPFPX) and identification
      of its metabolites in plasma by thin-layer chromatography and high-performance
      liquid chromatography (HPLC). Analysis of human, mouse, and rat plasma extracts
      by HPLC identified four identical radioactive metabolites in each species. The
      low mass of radioligand administered to humans (0.5 - 5 nmol) prevented direct
      identification of metabolites. However, incubating liver microsomes with CPFPX
      and analysis by means of liquid chromatography-mass spectrometry (LC-MS)
      identified seven compounds, four having the same retention times as the
      metabolites in human plasma. Analysis of microsomal metabolites by LC-MS
      identified five [M + H](+) ions of m/z equivalent to hydroxy derivatives, 339,
      one of m/z equivalent to an oxo derivative, m/z 337, and one of m/z equivalent to
      a difunctionalized oxo-desaturation species, m/z 335, which is prominent in rat
      and mouse plasma and is the main metabolite in human plasma. An [M + H](+) ion
      corresponding to a N-dealkylated derivative was not detected. Thus, like the
      natural methylxanthines, CPFPX seems to undergo oxidation by liver microsomes
      but, unlike those methylxanthines, dealkylation did not occur. LC-MS experiments
      with "in source" fragmentation identified the cyclopentyl moiety to be the most
      functionalized part of the molecule by liver microsomes and in vivo oxidations.
      Except for two metabolites, hydroxylated at the N1 propyl chain, all oxidative
      modifications found took place at the cyclopentyl ring.

PMID- 16415117
TI  - In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models
      and antimalarial activity of major metabolites on Plasmodium falciparum.
AB  - Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on
      laboratory clones and on field isolates. So far, no resistance was documented in
      Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine,
      based on experiments using animal and human hepatic models, is proposed.
      Ferroquine is metabolized mainly via an oxidative pathway into the major
      metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine.
      Some other minor metabolic pathways were also identified. Cytochrome P450
      isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are
      mainly involved in ferroquine oxidation. The metabolites were synthesized and
      tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P.
      falciparum strains. According to the results, the activity of the two main
      metabolites decreased compared with that of ferroquine; however, the activity of
      the mono-N-demethyl derivative is significantly higher than that of chloroquine
      on both strains, and the di-N-demethyl derivative remains more active than
      chloroquine on the chloroquine-resistant strain. These results further support
      the potential use of ferroquine against human malaria.

PMID- 16415118
TI  - S-2-pentyl-4-pentynoic hydroxamic acid and its metabolite s-2-pentyl-4-pentynoic
      acid in the NMRI-exencephaly-mouse model: pharmacokinetic profiles, teratogenic
      effects, and histone deacetylase inhibition abilities of further valproic acid
      hydroxamates and amides.
AB  - Structure-activity relationship studies of valproic acid (VPA) derivatives have
      revealed a quantitative correlation between histone deacetylase (HDAC) inhibition
      and induction of neural tube defects (NTDs) in the NMRI-exencephaly-mouse model,
      but this correlation has been, so far, limited to congeners with a carboxylic
      acid function. Whereas the classical HDAC inhibitor trichostatin A is active only
      as a hydroxamate but not as a carboxylic acid, we found that neither VPA amides
      nor hydroxamates inhibit HDACs, but can cause NTDs; e.g., 2-pentyl-4-pentynoic
      hydroxamic acid with its S-enantiomer being the potent teratogen. We therefore
      investigated the hypothesis that hydroxamic acid derivatives of VPA might be
      metabolized in vivo and may possibly be pro-teratogenic, as had been shown for
      valpromide but not valproic hydroxamic acid. We developed two stereoselective
      quantification methods based on chiral derivatization of VPA hydroxamates with
      (1R,2S,5R)-(-)-menthylchloroformate and carboxylic acid derivatives with (S)-(-)
      1-naphthylethylamine, followed by gas chromatography-nitrogen phosphor detector
      analysis of biological samples. We then determined the pharmacokinetic profiles
      of S-2-pentyl-4-pentynoic hydroxamic acid and of S-2-pentyl-4-pentynoic acid in
      mice. S-2-Pentyl-4-pentynoic hydroxamic acid was found to be extensively
      metabolized to the corresponding carboxylic acid without affecting the
      stereochemistry at position C2. Furthermore, the metabolite S-2-pentyl-4
      pentynoic acid was found to be very stable in vivo, with an extended half-life of
      4.2 h compared with that of VPA, 1.4 h. Comparison of the individual HDAC
      inhibition abilities of additional VPA amides and hydroxamates, as measured by
      cellular and enzymatic assays, led us to the conclusion that both classes of VPA
      derivatives can be pro-teratogenic.

PMID- 16415119
TI  - Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet
      agent, with the cytochromes P450.
AB  - The biotransformation of prasugrel to R-138727 (2-[1-2-cyclopropyl-1-(2
      fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid) involves
      rapid deesterification to R-95913 (2-[2-oxo-6,7-dihydrothieno[3,2-c]pyridin-5(4H)
      yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone) followed by cytochrome P450 (P450)
      mediated formation of R-138727, the metabolite responsible for platelet
      aggregation. For identification of the P450s responsible for the formation of the
      active metabolite, the current studies were conducted with R-95913 as the
      substrate. Incubations required supplementation with reduced glutathione.
      Hyperbolic kinetics (K(m) 21-30 microM), consistent with a single enzyme
      predominating, were observed after incubations with human liver microsomes.
      Correlation analyses revealed a strong relationship between R-138727 formation
      and CYP3A-mediated midazolam 1'-hydroxylation (r(2) = 0.98; p < 0.001) in a bank
      of characterized human liver microsomal samples. The human lymphoblast-expressed
      enzymes capable of forming R-138727, in rank order of rates, were
      CYP3A4>CYP2B6>CYP2C19 approximately CYP2C9>CYP2D6. A monoclonal antibody to
      CYP2B6 and the CYP3A inhibitor ketoconazole substantially inhibited R-138727
      formation, whereas inhibitors of CYP2C9 (sulfaphenazole) and CYP2C19 (omeprazole)
      did not. Scaling of in vitro intrinsic clearance values from expressed enzymes to
      the whole liver using a relative abundance approach indicated that either CYP3A4
      alone or CYP3A4 and CYP2B6 are the major contributors to R-138727 formation. R
      95913 and R-138727 were also examined for their ability to inhibit metabolism
      mediated by five P450s. R-138727 did not inhibit the P450s tested. In vitro, R
      95913 inhibited CYP2C9, CYP2C19, CYP2D6, and CYP3A, with K(i) values ranging from
      7.2 microM to 82 microM, but did not inhibit CYP1A2. These K(i) values exceed
      circulating concentrations in humans by 3.8- to 43-fold. Therefore, neither R
      95913 nor R-138727 is expected to substantially inhibit the P450-mediated
      metabolism of coadministered drugs.

PMID- 16415120
TI  - Effects of herbal extracts on the function of human organic anion-transporting
      polypeptide OATP-B.
AB  - Most known interactions between herbal extracts and drugs involve the inhibition
      of drug-metabolizing enzymes, but little is yet known about the possible role of
      transporters in these interactions. In this study, we have examined the effects
      of herbal extracts used in dietary supplements on the function of organic anion
      transporting polypeptide B (OATP-B; OATP2B1), which is expressed on human
      intestinal epithelial cells and is considered to be involved in the intestinal
      absorption of various drugs. Specifically, the effects of 15 herbal extracts on
      uptake of estrone-3-sulfate, a typical OATP-B substrate, by human embryonic
      kidney 293 cells stably expressing OATP-B were evaluated. At concentration levels
      considered likely to be attainable in the human intestine, extracts of bilberry,
      echinacea, green tea, banaba, grape seed, ginkgo, and soybean potently inhibited
      estrone-3-sulfate uptake by 75.5, 55.5, 82.1, 61.1, 64.5, 85.4, and 66.8%,
      respectively (P < 0.01). The inhibitory effect of ginkgo leaf extract was
      concentration-dependent (IC(50) = 11.2 +/- 3.3 microg/ml) and reversible.
      Moreover, flavonol glycosides and catechins significantly inhibited the function
      of OATP-B, suggesting that the inhibitory effects of the herbal extracts on OATP
      B may be primarily attributable to flavonoids. The extracts of mulberry, black
      cohosh, and Siberian ginseng moderately (but significantly) inhibited estrone-3
      sulfate uptake by 39.1, 47.2, and 49.2%, respectively (P < 0.05). Extracts of
      barley, Job's tears, rutin, rafuma, and passionflower were ineffective. These
      results suggest that coadministration of some dietary supplements may decrease
      the absorption of orally administered substrates of OATP-B.

PMID- 16415121
TI  - Characterization of cytochrome P450 expression in murine embryonic stem cell
      derived hepatic tissue system.
AB  - An in vitro system for liver organogenesis from murine embryonic stem (ES) cells
      has been recently established. This system is expected to be applied to the
      development of a new drug metabolism assay system that uses ES cells as a
      substitute for animal experiments. The objective of this study was to elucidate
      the drug metabolism profiles of the murine ES cell-derived hepatic tissue system
      compared with those of primary cultures of murine adult and fetal hepatocytes.
      The expression of the genes of the cytochrome P450 (P450) family, such as Cyp2a5,
      Cyp2b10, Cyp2c29, Cyp2d9, Cyp3a11, and Cyp7a1, was observed in the murine ES cell
      derived hepatic tissue system at 16 days and 18 days after plating (A16 and A18).
      To investigate the activities of these P450 family enzymes in the murine ES cell
      derived hepatic tissue system at A16 and A18, testosterone metabolism in this
      system was analyzed. Testosterone was hydroxylated to 6beta-hydroxytestosterone
      (6beta-OHT), 16alpha-OHT, 2alpha-OHT, and 2beta-OHT in this system, and was not
      hydroxylated to 15alpha-OHT, 7alpha-OHT, and 16beta-OHT. This metabolism profile
      was similar to that of fetal hepatocytes and different from that of adult
      hepatocytes. Furthermore, pretreatment with phenobarbital resulted in a 2.5- and
      2.6-fold increase in the production of 6beta-OHT and 16beta-OHT. Thus, evidence
      for drug metabolic activities in relation to P450s has been demonstrated in this
      system. These results in this system would be a stepping stone of the research on
      the development and differentiation to adult liver.

PMID- 16415122
TI  - In silico and in vitro screening for inhibition of cytochrome P450 CYP3A4 by
      comedications commonly used by patients with cancer.
AB  - Cytochrome P450 3A4 (CYP3A4) is the major enzyme responsible for phase I drug
      metabolism of many anticancer agents. It is also a major route for metabolism of
      many drugs used by patients to treat the symptoms caused by cancer and its
      treatment as well as their other illnesses, for example, cardiovascular disease.
      To assess the ability to inhibit CYP3A4 of drugs most commonly used by our
      patients during cancer therapy, we have made in silico predictions based on the
      crystal structures of CYP3A4. From this set of 33 common comedicated drugs, 10
      were predicted to be inhibitors of CYP3A4, with the antidiarrheal drug loperamide
      predicted to be the most potent. There was significant correlation (r(2) = 0.75
      0.66) between predicted affinity and our measured IC(50) values, and loperamide
      was confirmed as a potent inhibitor (IC(50) of 0.050 +/- 0.006 microM). Active
      site docking studies predicted an orientation of loperamide consistent with
      formation of the major (N-demethylated) metabolite, where it interacts with the
      phenylalanine cluster and Arg-212 and Glu-374; experimental evidence for the
      latter interaction comes from the approximately 12-fold increase in K(M) for
      loperamide observed for the Glu-374-Gln mutant. The commonly prescribed drugs
      loperamide, amitriptyline, diltiazem, domperidone, lansoprazole, omeprazole, and
      simvastatin were identified by our in silico and in vitro screens as relatively
      potent inhibitors of CYP3A4 that have the potential to interact with cytotoxic
      agents to cause adverse effects, highlighting the likelihood of drug-drug
      interactions affecting chemotherapy treatment.

PMID- 16415123
TI  - Epidermal growth factor-mediated activation of the map kinase cascade results in
      altered expression and function of ABCG2 (BCRP).
AB  - Epidermal growth factor (EGF) is a multifunctional growth factor known to play a
      major role in proliferation and differentiation processes. EGF-induced
      differentiation is a prerequisite for function of various cell types, among them
      cytotrophoblasts, a functionally important cellular fraction in human placenta.
      Stimulation of cytotrophoblasts with EGF results in formation of a multinuclear
      syncytium representing the feto-maternal interface, which protects the fetus
      against exogenous substances. It is well established that part of this protection
      system is based on ATP-binding cassette (ABC) transporters such as ABCG2 (breast
      cancer resistance protein, BCRP). However, little is known about regulation of
      transport proteins in the framework of EGF-mediated cellular differentiation. In
      the present work we show a significant increase of ABCG2 expression by EGF in
      cytotrophoblasts, BeWo, and MCF-7 cells on both mRNA and protein levels. This
      increase resulted in decreased sensitivity to the ABCG2 substrates mitoxantrone
      and topotecan. In each cell type, EGF increases expression of ABCG2 by activation
      of mitogen-activated protein kinase cascade via phosphorylation of extracellular
      regulated kinase (ERK)1/2 and c-jun NH-terminal kinase/stress-activated protein
      kinase (JNK/SAPK). Consequently, the increase of ABCG2 by EGF was abolished by
      pretreatment of cells with the tyrosine kinase inhibitor 4-(3-chloroanillino)-6,7
      dimethoxyquinazoline (AG1478) or the mitogen-activated protein kinase kinase
      inhibitor 2'-amino-3'methoxyflavone (PD 98059), thereby reestablishing
      sensitivity toward mitoxantrone. Moreover, analysis of ABCG2 expression during
      placental development revealed a significant increase in preterm versus term
      placenta. Taken together, our data show regulation of ABCG2 expression by EGF. In
      view of EGF signal transduction as a target for drugs (e.g., gefitinib), which
      are in turn substrates and/or inhibitors of ABCG2, this regulation has
      therapeutic consequences.

PMID- 16415124
TI  - ATP-dependent transport of rosuvastatin in membrane vesicles expressing breast
      cancer resistance protein.
AB  - MDR1/ABCB1, MRP2/ABCC2, and breast cancer resistance protein (BCRP)/ABCG2 are
      expressed in the liver and intestine and contribute to the disposition of many
      drugs. Rosuvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor for the
      treatment of patients with dyslipidemia, is primarily excreted via bile as
      unchanged drug. The present study was designed to determine whether rosuvastatin
      is transported by MDR1, MRP2, and BCRP. The apparent permeability value for
      rosuvastatin across MDR1-Madin-Darby canine kidney cells was low ( approximately
      8 nm/s), and no directional transport was observed. Rosuvastatin uptake into
      control Sf9 membranes and membranes expressing MRP2 was similar in the presence
      or absence of GSH. In contrast, ATP dramatically stimulated rosuvastatin uptake
      into membranes expressing BCRP, but not control membranes. Rosuvastatin transport
      occurred into an osmotically sensitive space and was saturable. An Eadie-Hofstee
      analysis suggested that there were two transport sites in BCRP, with an apparent
      K(m) of 10.8 muM for the high affinity site and 307 microM for the low affinity
      site. These data demonstrate that rosuvastatin is transported efficiently by BCRP
      and suggest that BCRP plays a significant role in the disposition of
      rosuvastatin.

PMID- 16415126
TI  - Empirical validation of a rat in vitro organ slice model as a tool for in vivo
      clearance prediction.
AB  - Tissue slices have been shown to be a valuable tool to predict metabolism of
      novel drugs. However, besides the numerous advantages of their use for this
      purpose, some potential drawbacks also exist, including reported poor penetration
      of drugs into the inner cell layers of slices and loss of metabolic capacity
      during prolonged incubation, leading to underprediction of metabolic clearance.
      In the present study, we empirically identified (and quantified) sources of
      underprediction using rat tissue slices of lung, intestine, kidney, and liver and
      found that thin liver slices (+/-100 mum) metabolized model substrates (7
      hydroxycoumarin, testosterone, warfarin, 7-ethoxycoumarin, midazolam,
      haloperidol, and quinidine) as rapidly as isolated hepatocytes. Furthermore, it
      was found that organ slices remain metabolically active for sufficient periods of
      incubation, enabling study of the kinetics of low clearance compounds. In
      addition, we determined the influence of albumin on the clearance prediction of
      six model substrates. For three of these substrates, the intrinsic clearance in
      the presence of albumin was approximately 3 times higher than that obtained from
      incubations without albumin, but corrected for unbound fraction. This resulted in
      a much more accurate prediction of in vivo whole body metabolic clearance for
      these compounds. Collectively, these results show that drawbacks of the use of
      slices for clearance prediction are largely surmountable. Provided that thin
      liver slices and physiological albumin concentration are used, whole body
      metabolic clearance is predicted with acceptable (2-fold) accuracy with organ
      slices. These results emphasize the applicability of organ slices in this field
      of research.

PMID- 16415125
TI  - An evaluation of methods for the reconstitution of cytochromes P450 and NADPH
      P450 reductase into lipid vesicles.
AB  - Two methods (cholate dialysis and cholate gel filtration) used to incorporate
      cytochromes P450 (P450s) and reductase into unilamellar phospholipid vesicles
      were compared with a standard reconstituted system (SRS) in which the proteins
      were reconstituted with preformed liposomes. Both cholate dialysis and gel
      filtration methods were comparable in their ability to physically incorporate
      reductase and either CYP2B4 or CYP1A2 into phospholipid, as determined by the
      elution of enzymes in the void volume using size exclusion chromatography (mol.
      wt. cutoff -5,000,000). Incorporation of these proteins was more efficient with
      both cholate methods than when reductase and P450 were mixed with preformed
      vesicles (SRS). Using either cholate method, more than 85% of the P450 was
      physically incorporated into the phospholipid vesicles, whereas less than 40% of
      the P450 was physically incorporated into the phospholipid vesicles using the
      SRS. Catalytic activities of the vesicular preparations of reductase and either
      CYP1A2 or CYP2B4 also were significantly higher than those resulting from the SRS
      using dilaurylphosphatidylcholine. Although both cholate dialysis and gel
      filtration methods improved protein incorporation when compared with
      preincubation of proteins with preformed liposomes, reductase incorporation was
      dependent on the relative amount of reductase used. Reductase incorporation was
      complete at a 0.2:1 reductase/P450 ratio; however, the efficiency of
      incorporation decreased to less than 50% at equimolar reductase/P450.
      Interestingly, reductase incorporation was higher in the presence of CYP1A2 than
      with CYP2B4. Both cholate methods resulted in the loss of a proportion of
      spectrally detectable carbon monoxyferrous P450, resulting from incubation of the
      proteins with detergent.

PMID- 16415129
TI  - CT angiography of peripheral arterial disease.
AB  - Lower-extremity computed tomographic (CT) angiography (ie, peripheral CT
      angiography) is increasingly used to evaluate patients with peripheral arterial
      disease. It is therefore increasingly important for all vascular specialists to
      become familiar with the strengths and limitations of this new technique. The
      aims of this review are to explain the principles of scanning and injection
      technique for a wide range of CT scanners, to explain and illustrate the
      properties of current image postprocessing tools for effective visualization and
      treatment planning, and to provide an overview of current clinical applications
      of peripheral CT angiography.

PMID- 16415127
TI  - Identification of new antimalarial drugs by linear discriminant analysis and
      topological virtual screening.
AB  - OBJECTIVES: A quantitative structure-activity relationship study using a database
      of 395 compounds previously tested against chloroquine-susceptible strains of the
      blood stages of Plasmodium falciparum to predict new in vitro antimalarial drugs
      has been developed. METHODS: Topological indices were used as structural
      descriptors and were related to antimalarial activity by using linear
      discriminant analysis (LDA) and multilinear regression (MLR). Two discriminant
      equations were obtained (FD1 and FD2), which allowed us to carry out successful
      classification of 90% and 80% of compounds, respectively. The IC50 values of the
      compounds were introduced to get an MLR equation model suitable to predict their
      in vitro activities. RESULTS: Using this model, a set of 27 drugs against a
      chloroquine-susceptible clone (3D7) of P. falciparum have been selected and
      evaluated in vitro. Among these drugs are monensin, nigericin, vincristine,
      vindesine, ethylhydrocupreine and salinomycin with in vitro IC50s at nanomolar
      concentrations (0.3, 0.4, 2, 6, 26 and 188 nM, respectively). Other compounds
      such as hycanthone, amsacrine, aphidicolin, bepridil, amiodarone, ranolazine and
      triclocarban showed in vitro IC50 values below 5 microM in the mathematical
      model. CONCLUSIONS: These results demonstrate the usefulness of the approach for
      the selection and design of new lead drugs active against P. falciparum.

PMID- 16415130
TI  - Endovascular and interventional procedures in obese patients: a review of
      procedural technique modifications and radiation management.
AB  - As the prevalence of obesity in the United States continues to increase, the
      volume of endovascular and fluoroscopically guided procedures is also increasing.
      With obese patients, it often seems the only consideration is whether the table
      weight tolerance can accommodate the patient. This is a naive approach to
      performing procedures in obese patients, as there are multiple considerations
      involved in providing state-of-the-art endovascular and interventional care to
      obese patients. A growing collection of literature is beginning to surface
      regarding the appropriate modifications in the interventional care of these
      patients. This article reviews the relevant literature on this important subject.

PMID- 16415132
TI  - Chemoembolization in patients at high risk: results and complications.
AB  - PURPOSE: Transarterial chemoembolization (TACE) has become a standard treatment
      option for unresectable hepatocellular carcinoma (HCC) and is often used to
      palliate hepatic metastases. Many patients who are candidates for TACE present
      with poor hepatic reserve, advanced tumor stage with major portal vein (PV)
      invasion or thrombosis, and/or biliary dilation. These factors have been
      associated with a poor prognosis and increased complications after
      chemoembolization. Accordingly, these patients are classified as being at high
      risk and may not be considered for therapy. The aim of this study is to evaluate
      the results of TACE in these patients. MATERIALS AND METHODS: Over a period of 5
      years, 141 patients underwent 355 TACE procedures. Thirty-six patients (26%) were
      in the high-risk group as a result of major PV thrombosis, increased serum
      bilirubin level (>2 mg/dL), and/or intrahepatic biliary dilation. HCC was the
      underlying tumor in 60% of patients. Thirty-seven percent of patients had Child
      Pugh class B/C disease. Patients in the high-risk group received more selective
      embolization with fewer particles and fewer procedures (2.0 vs 2.7; P < .04).
      RESULTS: Patients in the high-risk group were more likely to have HCC (83% vs
      51%; P < .01) and were also more likely to have advanced disease according to
      Child-Pugh classification versus patients in the low-risk group (49% vs 20%; P <
      .01). The overall complication rate was 4.3%, with no significant difference in
      complication rate between groups (3.2% vs 8.2%; P = .12). The overall 30-day
      mortality rate was 2.3%, and no significant difference in 30-day mortality rate
      was observed between the high- and low-risk groups (5.5% vs 1.4%; P = .11). A
      trend toward increased survival in the low-risk group did not reach statistical
      significance. CONCLUSIONS: These data suggest that patients with advanced disease
      and decreased hepatic reserve who are treated with TACE exhibit no significant
      increase in morbidity or mortality and no significant decrease in survival. With
      variations in technique, TACE can be performed safely in patients with the
      relative risk factors that may classify them in high-risk groups.

PMID- 16415131
TI  - Clinical and anatomic outcomes after embolotherapy of pulmonary arteriovenous
      malformations.
AB  - PURPOSE: To assess long-term clinical and imaging results of technically
      successful pulmonary arteriovenous malformation (AVM) embolization. MATERIALS AND
      METHODS: One hundred fifty-five patients with pulmonary AVMs underwent
      embolization during a period of 3 years. Recommended follow-up included clinical
      assessment, helical computed tomography, and physiologic evaluation within 1 year
      and then every 5 years. RESULTS: Hereditary hemorrhagic telangiectasia was
      present in 148 patients (95%). Four hundred fifteen pulmonary AVMs were occluded
      during 205 procedures. Clinical follow-up was available in all patients over 3-7
      years and imaging follow-up was available in 144 patients (393 lesions) over 1-7
      years (mean, 2.9 y). Problems related to pulmonary AVMs occurred in 35 patients
      (23%) at 42 time points: 22 patients with 23 symptomatic events and 17 patients
      with 19 asymptomatic events. Symptoms resulted from growth of nonembolized
      pulmonary AVMs (n = 19), residual embolized pulmonary AVMs (n = 5), or both (n =
      2). Symptoms consisted of respiratory manifestations (n = 13), cerebral ischemia
      (n = 4), brain abscess (n = 5), hemoptysis (n = 3), and seizure (n = 1). Imaging
      showed pulmonary AVM involution in 97% of embolized lesions and 11 residual
      lesions (2.8%) in 10 patients (6.9%). These were caused by recanalization (n =
      7), presence of an accessory feeding artery (n = 1), pulmonary collateral vessels
      (n = 1), and bronchial collateral vessels (n = 2). CT detected 10 of the 11
      residual lesions. Imaging detected 97 previously small pulmonary AVMs that had
      enlarged to a significant size in 28 patients (18%), 15 of whom were symptomatic
      and 13 of whom were asymptomatic. CONCLUSIONS: Clinical and anatomic evaluation
      after pulmonary AVM embolization is important to detect persistent or reperfused
      lesions and enlarging lesions, with the latter more common. Patients with
      persistent, reperfused, or enlarging lesions often have symptoms, but a
      significant minority of patients are asymptomatic. More frequent assessment may
      improve detection before the onset of symptoms.

PMID- 16415133
TI  - Portal flow and arterioportal shunting after transjugular intrahepatic
      portosystemic shunt creation.
AB  - PURPOSE: It was postulated that a transjugular intrahepatic portosystemic shunt
      (TIPS) produces arterioportal shunting and accounts for reversed flow in the
      intrahepatic portal veins (PVs) after creation of the TIPS. This study sought to
      quantify this shunting in patients undergoing TIPS creation and/or revision with
      use of a direct catheter-based technique and by measuring changes in blood
      oxygenation within the TIPS and the PV. MATERIALS AND METHODS: This prospective
      study consisted of 26 patients. Median Model for End-stage Liver Disease and
      Child-Pugh scores were 13 and 9, respectively. Primary TIPS creation was
      attempted in 21 patients and revision of failing TIPS was undertaken in five. In
      two patients, TIPS creation was unsuccessful. All TIPS creation procedures but
      one were performed with use of polytetrafluoroethylene-covered stent-grafts. Flow
      within the main PV (Q(portal)) was measured with use of a retrograde
      thermodilutional catheter before and after TIPS creation/revision, and TIPS flow
      (Q(TIPS)) was measured at procedure completion. The amount of arterioportal
      shunting was assumed to be the increase between final Q(portal) and Q(TIPS),
      assuming Q(TIPS) was equivalent to the final Q(portal) plus the reversed flow in
      the right and left PVs. Oxygen saturation within the TIPS and the PV was
      determined from samples obtained during TIPS creation and revision. RESULTS: Mean
      Q(portal) before TIPS creation was 691 mL/min; mean Q(portal) after TIPS creation
      was 1,136 mL/min, representing a 64% increase (P = .049). Mean Q(TIPS) was 1,631
      mL/min, a 44% increase from final Q(portal) (P = .0009). Among cases of revision,
      baseline Q(portal) was 1,010 mL/min and mean Q(portal) after TIPS revision was
      1,415 mL/min, a 40% increase. Mean Q(TIPS) was 1,693 mL/min, a 20% increase from
      final Q(portal) (P = .42). Arterioportal shunting rates were 494 mL/min after
      TIPS creation and 277 mL/min after TIPS revision, representing 30% of total
      Q(TIPS) after TIPS creation and 16% of Q(TIPS) after TIPS revision. No increase
      in oxygen tension or saturation was seen in the PV or TIPS compared with initial
      PV levels. Q(TIPS) did not correlate with the portosystemic gradient. CONCLUSION:
      TIPS creation results in significant arterioportal shunting, with less
      arterioportal shunting seen among patients who undergo TIPS revision. Further
      work is necessary to correlate Q(TIPS) with the risk of hepatic encephalopathy
      and liver failure.

PMID- 16415134
TI  - Biliary duct ablation with N-butyl cyanoacrylate.
AB  - PURPOSE: To assess the efficacy of percutaneous insertion of n-butyl
      cyanoacrylate (NBCA) in the ablation of bile ducts in patients with persistent
      postsurgical bile leaks in which traditional means of treatment have failed.
      MATERIALS AND METHODS: Ablation of bile ducts with NBCA was performed in six
      patients (two men and four women). The average length of follow-up was 27 months
      (range, 13-46 months). Four patients presented after hepatic lobectomy with a
      persistent bile leak, one patient presented after cholecystectomy with a
      chronically obstructed bile duct, and one patient presented after cholecystectomy
      from intraoperative bile duct injury. After access to the biliary system was
      obtained, a cholangiogram was obtained. After the desired duct was isolated, it
      was copiously irrigated with saline solution. A glue solution containing NBCA
      glue, Ethiodol, and tantalum powder was delivered into the duct through a
      polyethylene catheter that had been irrigated with dextrose solution. RESULTS:
      Four patients had problems arising from isolated segmental ductal systems that
      had no communication with the normal biliary ductal system and were treated
      successfully on the first attempt. In two patients, there was communication to
      the main biliary ductal system and a persistent bile leak occurred that required
      placement of a coil and a second final gluing procedure. The only complication
      observed was unintentional spillage of glue into the main biliary system in one
      patient, which was ultimately clinically insignificant. CONCLUSIONS: The use of
      NBCA glue in obliteration of bile ducts is a safe procedure with excellent
      results in patients with complications from isolated segmental ducts. Although a
      repeat procedure may be necessary if the duct communicates with the main biliary
      tree, the procedure can decrease the morbidity associated with chronic external
      biliary drainage.

PMID- 16415135
TI  - The risk of new osteoporotic vertebral compression fractures in the year after
      percutaneous vertebroplasty.
AB  - PURPOSE: To prospectively assess the incidence, location, and possible causative
      mechanisms of new vertebral compression fractures (VCFs) in 66 symptomatic
      patients with osteoporotic VCFs treated with percutaneous vertebroplasty (PV) and
      to study the relation between new VCFs and back pain symptoms. MATERIALS AND
      METHODS: Sixty-six patients with 102 painful symptomatic VCFs were treated with
      PV. All patients had baseline total spinal magnetic resonance (MR) imaging.
      Follow-up MR imaging was performed at 3, 6, and 12 months to locate new VCFs.
      Visual analog scales for pain and pain medication consumption were used to assess
      clinical outcomes. The following characteristics were compared in patients with
      new VCFs after PV versus patients without new VCFs: patient age, sex, presence of
      secondary osteoporosis, bone mineral density, number of preexisting VCFs, shape
      and grade of VCFs, type of bone cement used for PV, volume of injected cement,
      and cement leakage in intervertebral disc spaces. RESULTS: Sixteen of 66 patients
      had 26 new VCFs during 1 year of follow-up after PV. Most new VCFs occurred
      within 3 months of PV, half of new VCFs appeared in levels adjacent to treated
      levels, and half of the new VCFs were symptomatic. The presence of more than two
      preexisting VCFs was the only independent risk factor for the development of a
      new VCF. CONCLUSIONS: New VCFs occurred after PV in 24% of patients. Half of new
      VCFs occurred in levels adjacent to treated levels and half were symptomatic. The
      presence of more than two preexisting VCFs was the only independent risk factor
      for the development of a new VCF.

PMID- 16415136
TI  - Radiation dose and risk from fluoroscopically guided percutaneous transhepatic
      biliary procedures.
AB  - PURPOSE: To estimate radiation dose and associated risks after fluoroscopically
      guided percutaneous transhepatic biliary (PTB) drainage and stent implantation
      procedures. MATERIALS AND METHODS: Organ and effective doses, normalized to dose
      area product (DAP), were estimated for PTB procedures with use of a Monte Carlo
      transport code and an adult mathematical phantom. Exposure parameters from 51
      consecutive patients were used to determine average examination parameters for
      biliary drainage and stent implantation procedures. Thermoluminescent dosimeters
      were used in an anthropomorphic phantom to verify Monte Carlo calculations.
      Radiation-induced cancer and genetic risks were estimated. RESULTS: The results
      consist of doses normalized to DAP so patient dose from any technique and x-ray
      unit can be easily calculated for left and right biliary access and for separate
      or combined biliary and metallic stent implantation sessions. A good agreement
      was found between Monte Carlo-calculated data and data derived from
      thermoluminescent dosimetry. The average effective dose varied from 1.8 to 5.4
      mSv depending on procedure approach (left vs right access) and procedure scheme.
      A maximum effective dose of 13 mSv was estimated for 30 minutes of fluoroscopy.
      CONCLUSIONS: Doses delivered to patients undergoing PTB procedures are comparable
      to those that arise from computed tomography protocols. Radiation-induced cancer
      risk may be considerable for young patients undergoing PTB drainage and stent
      implantation procedures.

PMID- 16415137
TI  - Operating expenses for the diagnosis and treatment of peripheral vascular disease
      in an academic interventional radiology department: cost calculations according
      to a microeconomic method.
AB  - PURPOSE: A correct understanding of the true costs of a procedure is necessary to
      make informed decisions in cost-effectiveness analyses. The actual comprehensive
      costs of performing cardiovascular and interventional radiology (CVIR) procedures
      were analyzed in the present study, as opposed to charges or ratios of costs to
      charges (RCCs), as often used in the literature. MATERIALS AND METHODS: Costs
      included labor, equipment, administration, facility establishment and
      maintenance, overhead, and consumable supplies. Cost identification was initially
      performed with use of an hourly rate that reflected the cost of operating the
      CVIR section. This was then combined with the costs of the consumable supplies
      used during each type of procedure. Eight types of vascular procedures were
      studied in 235 consecutive patients to determine mean procedure duration and
      supplies consumption. Costs were then compared with charges and RCCs of these
      procedures. RESULTS: The hourly rate for operating one angiography suite was 690
      dollars. Average cost by procedure, including hourly rate plus consumable
      supplies, were: aortic arteriogram, 1,442 dollars; aortobifemoral arteriogram,
      1,554 dollars; unilateral limb arteriogram, 1,307 dollars; simple iliac or
      femoropopliteal angioplasty, 2,119 dollars; arterial stent placement, 2,780
      dollars; percutaneous thrombectomy, 1,998 dollars; arterial in situ thrombolysis,
      3,133 dollars; and arteriogram after thrombolysis, 926 dollars. RCCs calculated
      for each procedure ranged from 0.39 (thrombectomy) to 1.92 (control arteriography
      during or after thrombolysis) and were lower than expected based on previous
      reports. CONCLUSIONS: The average actual costs of several common diagnostic and
      therapeutic procedures for peripheral vascular occlusive disease were
      established, allowing determination of the relative importance of different cost
      components. This methodology may serve as a template for future cost analyses.

PMID- 16415138
TI  - Contrast material-enhanced visualization of the ablation medium for magnetic
      resonance-monitored ethanol injection therapy: imaging and safety aspects.
AB  - PURPOSE: This study was performed to test whether the dissociation rate of free
      Gd3+ ions from gadoterate meglumine is significantly increased when the contrast
      agent is dissolved in ethanol and whether the magnetic resonance (MR) signal of
      gadolinium/ethanol solutions is enhanced to a degree that promises reliable
      detection during MR imaging-guided intralesional administration, such as for the
      treatment of low-flow venous malformations. MATERIALS AND METHODS: The apparent
      gadoterate meglumine-induced enhancement of the longitudinal proton relaxation
      rate of sterile ethanol/water solutions, stored at a temperature of 24 degrees C
      +/- 5 degrees C in the dark, was monitored for 2 weeks. The content of
      dissociated Gd3+ ions was determined after 6 and 8.5 months of storage. The
      signal difference between contrast agent/ethanol solutions and muscle tissue was
      assessed with imaging at 0.5 T and 1.5 T. RESULTS: Commercialized gadoterate
      meglumine diluted with 94% ethanol was not shown to have released toxic Gd3+
      during storage times that exceed its physiologic circulation and excretion times
      after intravenous injection by a factor of more than 100. A maximum dissociation
      rate of 0.05% per month was estimated from the detection limit of the analysis.
      The apparent molar relaxivity of the contrast agent in the mixtures varied by
      less than 0.1 L/mmol per second with no temporal trend. Gradient-echo
      ethanol/muscle contrast increased with Gd concentrations to maximums of 15 mmol/L
      (at 0.5 T) and 25 mmol/L (at 1.5 T). CONCLUSIONS: Neither limited solubility nor
      release of Gd3+ ions could be identified as a general safety hazard associated
      with the application of gadoterate meglumine/ethanol solutions at Gd
      concentrations of 0.5-25 mmol/L, and such ablation mixtures could be efficiently
      and reliably visualized.

PMID- 16415139
TI  - Measurement of blood flow before and after embolization with use of fluorescent
      microspheres in an animal model.
AB  - PURPOSE: Catheter-directed embolization has become a widespread technique for the
      treatment of benign and malignant neoplasms. The mechanism whereby embolization
      leads to selective atrophy of these neoplasms is largely speculative. As a
      potential model for the large regional perfusion differences between normal and
      neoplastic tissues, renal perfusion was studied before and after catheter
      directed embolization. The working hypothesis was that embolization would create
      measurable changes in blood flow in the renal cortex and medulla. MATERIALS AND
      METHODS: Microspheres (l0 microm in diameter) containing a series of different
      fluorophores were injected into the arterial system before and after the renal
      arteries were embolized with a series of larger (100-300 microm) particulate
      embolic agents. The distribution of the microspheres in the renal cortex, renal
      medulla, and liver was analyzed by fluorescence microscopy as well as by
      extraction of the fluorophores. RESULTS: The distribution of the fluorescent
      microspheres was readily assessed by fluorescence microscopy or extraction of the
      fluorophores. Before embolization, the renal cortex received approximately three
      times more flow than the medulla. After embolization, perfusion of the renal
      cortex and medulla decreased in parallel. CONCLUSIONS: Fluorescent microspheres
      are a powerful tool for measuring the changes in flow that occur after catheter
      directed embolization. The fact that parallel decreases in flow were found in the
      renal cortex and medulla indicates that the distribution of each embolic agent
      was flow-directed. These results might provide insight into the mechanism of
      tumor atrophy after uterine artery embolization or hepatic chemoembolization.

PMID- 16415140
TI  - Placement of self-expanding stents with different diameters in the porcine venous
      system: an experimental study.
AB  - PURPOSE: To study the vascular histologic response after placement of oversized
      self-expanding stents in the porcine venous system. MATERIALS AND METHODS: Twenty
      four oversized stents (range of oversizing, 119.5%-216.0%) were deployed in
      jugular and iliac veins of six miniature pigs divided into two groups with follow
      up times of 1 and 3 months. Necropsy with histologic evaluation of each stent was
      performed, and the areas of neointimal proliferation were calculated with slices
      obtained during follow-up from each stent at 5 mm from the proximal and distal
      edges and at the midpoint. RESULTS: Neointimal proliferation was observed inside
      the stent lumen. All segments were patent in both groups. However, one jugular
      stent in the 1-month group and one jugular stent in the 3-month group had
      migrated at follow-up and were excluded from analysis. There were no significant
      differences in neointimal growth between the stent edges (proximal and distal)
      and middle segments of the stents at follow-up in the 1-month group (P = .970) or
      in the 3-month group (P = .694). Simple linear regression showed strong positive
      correlation between stent oversizing and neointimal proliferation in the 1-month
      model (r = 0.791; P < .001) and the 3-month model (r = 0.718; P < .001). There
      were no significant differences between 1-month and 3-month groups in the degree
      of neointimal proliferation (P = .072). Also, branched vessels showed no
      neointimal proliferation at their intersections with the stent-implanted
      segments. CONCLUSION: Stent oversizing showed a strong positive correlation with
      neointimal growth in each follow-up model in this study.

PMID- 16415141
TI  - Vascular injury caused by mechanical thrombectomy in porcine arteries: AKonya
      eliminator device versus Arrow-Trerotola percutaneous thrombolytic device.
AB  - PURPOSE: To compare vascular injuries induced by a nonrotational thrombectomy
      device equipped with an adjustable basket (the AKonya Eliminator [AKE] device)
      and the Arrow-Trerotola percutaneous thrombolytic device (PTD) in porcine
      external iliac arteries (EIAs). MATERIALS AND METHODS: The EIAs of nine domestic
      pigs underwent simulated thrombectomy with the AKE after the diameter of the
      basket had been adjusted to the vessel's diameter and with the PTD after motor
      activation. Three animals were euthanized immediately after treatment (group 1,
      acute), three after 1 week (group 2, subchronic), and three after 6 weeks (group
      3, chronic). Vessel diameters were measured angiographically at four anatomic
      locations at the three time points. A histologic grading system was established
      to quantify the degree of vascular injury and lumen compromise. Four other EIAs
      were treated with an "oversized" AKE basket and followed for 6 weeks. RESULTS:
      Histologically, the acute lesions in the AKE-treated vessels were more
      superficial than those in the PTD-treated vessels. In group 2, two of three PTD
      treated arteries occluded, and their subchronic injuries were more serious than
      those in the AKE-treated arteries. In group 3, all AKE-treated arteries remained
      patent, but one of the PTD-treated vessels occluded, and the lumen sizes of the
      PTD- and AKE-treated arteries differed significantly. After 6 weeks, there was no
      significant difference between arteries treated with the PTD and those treated
      with the oversized AKE in terms of diameter or histologic grading. CONCLUSIONS:
      The adjustable basket and hand-controlled operation of the AKE were significantly
      less injurious to the arterial wall than the constant-size PTD basket operated at
      3,000 rpm. Damage produced by the oversized AKE basket was similar to that
      produced by the PTD.

PMID- 16415142
TI  - Use of the Amplatzer Vascular Plug for embolization of a large retroperitoneal
      shunt during transjugular intrahepatic portosystemic shunt creation for gastric
      variceal bleeding.
AB  - A patient undergoing transjugular intrahepatic portosystemic shunt (TIPS)
      creation for gastric variceal hemorrhage was found to have a very large
      spontaneous splenorenal shunt requiring embolization after successful TIPS
      creation. The anticipated site of embolization was short and large in diameter
      and was therefore poorly suited for the use of conventional devices such as
      coils. Two Amplatzer Vascular Plugs and two platinum coils were used to occlude
      the shunt rapidly and completely.

PMID- 16415143
TI  - Bilateral multiple pulmonary arteriovenous malformations: endovascular treatment
      with the Amplatzer Vascular Plug.
AB  - Pulmonary arteriovenous malformation (AVM) is a rare vascular malformation of the
      lung that carries a considerable risk of serious complications such as cerebral
      embolism, brain abscess, and pulmonary hemorrhage. Embolization with coils or
      detachable balloons is currently the preferred treatment. Paradoxical
      embolization of coils and balloons may occur, especially in patients with large
      feeding arteries. This report describes an initial experience with the use of the
      Amplatzer Vascular Plug used for endovascular treatment of bilateral multiple
      pulmonary AVMs in an adult patient.

PMID- 16415145
TI  - Difficult retrieval of a retrievable inferior vena cava filter placed in an
      inverted orientation.
AB  - The present report describes a technique of retrieving a retrievable inferior
      vena cava (IVC) filter placed in an inverted orientation that had attached to the
      IVC wall. The filter was removed with difficulty via a combined jugular and
      femoral venous approach.

PMID- 16415144
TI  - Bioptome-assisted coil closure of large pulmonary arteriovenous malformations.
AB  - Large pulmonary arteriovenous malformations (AVMs) with feeding vessels larger
      than 5 mm cause significant right-to-left shunt resulting in cyanosis and need to
      be occluded as soon as they are diagnosed. Occlusion of such AVMs by simultaneous
      delivery of multiple coils was attempted in five patients and was successful in
      completely occluding the AVM in four of them. One patient had transient chest
      pain during the procedure, presumably as a result of coronary air embolism. A
      bioptome was used to hold the multiple coils together for optimal deployment and
      controlled release of the coils.

PMID- 16415147
TI  - Targeted drug delivery for refractory hemorrhagic Crohn disease.
AB  - Focal gastrointestinal inflammation and hemorrhage is a common problem associated
      with Crohn disease. The present report describes a case of chronic hemorrhage
      from an inflamed duodenum that was refractory to all endoscopic and systemic
      therapies, which was successfully treated with chemoembolization of the
      pancreaticoduodenal arcade with use of corticosteroids and gelatin sponge. The
      application of chemoembolization techniques need not be limited to treatment of
      malignancies.

PMID- 16415146
TI  - Management of postsurgical recurrence of hepatocellular carcinoma with rhenium
      188-HDD labeled iodized oil.
AB  - Surgical resection with partial hepatectomy is the treatment of choice in
      patients with hepatocellular carcinoma (HCC). However, after recurrence, which is
      common, such patients have limited therapeutic options. In the present report,
      transarterial radionuclide therapy (TART) with rhenium 188 HDD-labeled Lipiodol
      was used to treat a patient with postsurgical recurrence of HCC. The patient
      tolerated therapy well and the lesions were completely ablated with a single dose
      of 188Re; the patient is free of disease for 14 months. TART with 188Re-HDD
      Lipiodol appears to be a promising new therapy in case of HCC recurrence after
      partial hepatectomy and requires further investigation.

PMID- 16415148
TI  - Transrectal US-guided seminal vesiculography and ejaculatory duct recanalization
      and balloon dilation for treatment of chronic pelvic pain.
AB  - Ejaculatory duct obstruction (EDO) is an uncommon but correctable cause of
      infertility and male chronic pelvic pain. The condition is thought to be
      underdiagnosed, but the increased application of noninvasive imaging tools,
      specifically transrectal ultrasonography (US), has lead to greater recognition of
      EDO. Moreover, the development of minimally invasive therapies now offers
      comprehensive evaluation and treatment options with low morbidity for select
      patient groups. This report describes the technique of transrectal US-guided
      seminal vesiculography, percutaneous recanalization, and ejaculatory duct balloon
      dilation for EDO as a treatment for male chronic pelvic pain.

PMID- 16415149
TI  - Percutaneous CT-guided radiofrequency ablation of symptomatic bilateral adrenal
      metastases in a single session.
AB  - Percutaneous computed tomography (CT)-guided radiofrequency (RF) ablation has
      been used in the palliative treatment of symptomatic bilateral adrenal tumors,
      often with each tumor addressed separately over the course of multiple treatment
      sessions. In the present case, a 71-year-old man with a diagnosis of lung cancer
      and painful bilateral metastases to the adrenal glands underwent percutaneous CT
      guided RF thermal ablation of both adrenal masses in a single session (left
      adrenal mass, 4.7 cm; right adrenal mass, 4.3 cm), without occurrence of blood
      pressure instability or other acute complications. Measurement of plasma levels
      of cortisol, adrenocorticotropic hormone (ACTH), and glucose before and after RF
      ablation revealed transient changes that suggested preservation of endocrine
      feedback mechanisms. The patient experienced marked relief in pain bilaterally.
      By 5 days after the procedure, cortisol, ACTH, and glucose levels returned to
      preprocedural levels. On further follow-up at 6 months, the patient noted a lack
      of endocrine sequelae and continued pain relief.

PMID- 16415152
TI  - Placement of two filters for inferior vena caval duplication via a single femoral
      access and the left renal vein.

PMID- 16415150
TI  - Re: primary failure of uterine artery embolization: use of magnetic resonance
      imaging to select patients for repeated embolization.

PMID- 16415153
TI  - Re: transsternal approach for computed tomography-guided percutaneous
      radiofrequency ablation of a solitary lung metastasis.

PMID- 16415154
TI  - Re: renal artery stent placement: a simple technique to intubate the renal artery
      in difficult situations.

PMID- 16415155
TI  - The tumor suppressor menin regulates hematopoiesis and myeloid transformation by
      influencing Hox gene expression.
AB  - Menin is the product of the tumor suppressor gene Men1 that is mutated in the
      inherited tumor syndrome multiple endocrine neoplasia type 1 (MEN1). Menin has
      been shown to interact with SET-1 domain-containing histone 3 lysine 4 (H3K4)
      methyltransferases including mixed lineage leukemia proteins to regulate homeobox
      (Hox) gene expression in vitro. Using conditional Men1 knockout mice, we have
      investigated the requirement for menin in hematopoiesis and myeloid
      transformation. Men1 excision causes reduction of Hoxa9 expression, colony
      formation by hematopoietic progenitors, and the peripheral white blood cell
      count. Menin directly activates Hoxa9 expression, at least in part, by binding to
      the Hoxa9 locus, facilitating methylation of H3K4, and recruiting the methylated
      H3K4 binding protein chd1 to the locus. Consistent with signaling downstream of
      menin, ectopic expression of both Hoxa9 and Meis1 rescues colony formation
      defects in Men1-excised bone marrow. Moreover, Men1 excision also suppresses
      proliferation of leukemogenic mixed lineage leukemia-AF9 fusion-protein
      transformed myeloid cells and Hoxa9 expression. These studies uncover an
      important role for menin in both normal hematopoiesis and myeloid transformation
      and provide a mechanistic understanding of menin's function in these processes
      that may be used for therapy.

PMID- 16415156
TI  - A neurocomputational hypothesis for nicotine addiction.
AB  - We present a hypothetical neurocomputational model that combines a set of neural
      circuits at the molecular, cellular, and system levels and accounts for several
      neurobiological and behavioral processes leading to nicotine addiction. We
      propose that combining changes in the nicotinic receptor response, expressed by
      mesolimbic dopaminergic neurons, with dopamine-gated learning in action-selection
      circuits, suffices to capture the acquisition of nicotine addiction. We show that
      an opponent process enhanced by persistent nicotine-taking renders self
      administration rigid and habitual by inhibiting the learning process, resulting
      in long-term impairments in the absence of the drug. The model implies distinct
      thresholds on the dosage and duration for the acquisition and persistence of
      nicotine addiction. Our hypothesis unites a number of prevalent ideas on nicotine
      action into a coherent formal network for further understanding of compulsive
      drug addiction.

PMID- 16415157
TI  - Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and
      head and neck cancer.
AB  - The identification of tumor suppressor genes has classically depended on their
      localization within recurrent regions of loss of heterozygosity. According to
      Knudson's two-hit hypothesis, the remaining allele is lost, either genetically
      or, more recently identified, through epigenetic events. To date, retrospective
      analyses have determined promoter methylation as a common alternative alteration
      in cancer cells to silence cancer-related genes. Here we report an application of
      restriction landmark genomic scanning that allows for DNA methylation profiling
      along a region of recurrent loss of heterozygosity at chromosome 6q23-q24. This
      approach resulted in the identification of a tumor suppressor gene, TCF21, which
      is frequently lost in human malignancies. We demonstrate that TCF21 is expressed
      in normal lung airway epithelial cells and aberrantly methylated and silenced in
      the majority of head and neck squamous cell carcinomas and non-small-cell lung
      cancers analyzed. TCF21 is known to regulate mesenchymal cell transition into
      epithelial cells, a property that has been shown to be deficient in carcinomas.
      We further demonstrate that exogenous expression of TCF21 in cells that have
      silenced the endogenous TCF21 locus resulted in a reduction of tumor properties
      in vitro and in vivo.

PMID- 16415158
TI  - Dissociation of face-selective cortical responses by attention.
AB  - We studied attentional modulation of cortical processing of faces and houses with
      functional MRI and magnetoencephalography (MEG). MEG detected an early, transient
      face-selective response. Directing attention to houses in "double-exposure"
      pictures of superimposed faces and houses strongly suppressed the characteristic,
      face-selective functional MRI response in the fusiform gyrus. By contrast,
      attention had no effect on the M170, the early, face-selective response detected
      with MEG. Late (>190 ms) category-related MEG responses elicited by faces and
      houses, however, were strongly modulated by attention. These results indicate
      that hemodynamic and electrophysiological measures of face-selective cortical
      processing complement each other. The hemodynamic signals reflect primarily late
      responses that can be modulated by feedback connections. By contrast, the early,
      face-specific M170 that was not modulated by attention likely reflects a rapid,
      feed-forward phase of face-selective processing.

PMID- 16415159
TI  - Consistent simulations of multiple proxy responses to an abrupt climate change
      event.
AB  - Isotope, aerosol, and methane records document an abrupt cooling event across the
      Northern Hemisphere at 8.2 kiloyears before present (kyr), while separate
      geologic lines of evidence document the catastrophic drainage of the glacial
      Lakes Agassiz and Ojibway into the Hudson Bay at approximately the same time.
      This melt water pulse may have been the catalyst for a decrease in North Atlantic
      Deep Water formation and subsequent cooling around the Northern Hemisphere.
      However, lack of direct evidence for ocean cooling has lead to speculation that
      this abrupt event was purely local to Greenland and called into question this
      proposed mechanism. We simulate the response to this melt water pulse using a
      coupled general circulation model that explicitly tracks water isotopes and with
      atmosphere-only experiments that calculate changes in atmospheric aerosol
      deposition (specifically (10)Be and dust) and wetland methane emissions. The
      simulations produce a short period of significantly diminished North Atlantic
      Deep Water and are able to quantitatively match paleoclimate observations,
      including the lack of isotopic signal in the North Atlantic. This direct
      comparison with multiple proxy records provides compelling evidence that changes
      in ocean circulation played a major role in this abrupt climate change event.

PMID- 16415160
TI  - An auxin-driven polarized transport model for phyllotaxis.
AB  - Recent studies show that plant organ positioning may be mediated by localized
      concentrations of the plant hormone auxin. Auxin patterning in the shoot apical
      meristem is in turn brought about by the subcellular polar distribution of the
      putative auxin efflux mediator, PIN1. However, the question of what signals
      determine PIN1 polarization and how this gives rise to regular patterns of auxin
      concentration remains unknown. Here we address these questions by using
      mathematical modeling combined with confocal imaging. We propose a model that is
      based on the assumption that auxin influences the polarization of its own efflux
      within the meristem epidermis. We show that such a model is sufficient to create
      regular spatial patterns of auxin concentration on systems with static and
      dynamic cellular connectivities, the latter governed by a mechanical model. We
      also optimize parameter values for the PIN1 dynamics by using a detailed auxin
      transport model, for which parameter values are taken from experimental
      estimates, together with a template consisting of cell and wall compartments as
      well as PIN1 concentrations quantitatively extracted from confocal data. The
      model shows how polarized transport can drive the formation of regular patterns.

PMID- 16415161
TI  - A prehistory of Indian Y chromosomes: evaluating demic diffusion scenarios.
AB  - Understanding the genetic origins and demographic history of Indian populations
      is important both for questions concerning the early settlement of Eurasia and
      more recent events, including the appearance of Indo-Aryan languages and settled
      agriculture in the subcontinent. Although there is general agreement that Indian
      caste and tribal populations share a common late Pleistocene maternal ancestry in
      India, some studies of the Y-chromosome markers have suggested a recent,
      substantial incursion from Central or West Eurasia. To investigate the origin of
      paternal lineages of Indian populations, 936 Y chromosomes, representing 32
      tribal and 45 caste groups from all four major linguistic groups of India, were
      analyzed for 38 single-nucleotide polymorphic markers. Phylogeography of the
      major Y-chromosomal haplogroups in India, genetic distance, and admixture
      analyses all indicate that the recent external contribution to Dravidian- and
      Hindi-speaking caste groups has been low. The sharing of some Y-chromosomal
      haplogroups between Indian and Central Asian populations is most parsimoniously
      explained by a deep, common ancestry between the two regions, with diffusion of
      some Indian-specific lineages northward. The Y-chromosomal data consistently
      suggest a largely South Asian origin for Indian caste communities and therefore
      argue against any major influx, from regions north and west of India, of people
      associated either with the development of agriculture or the spread of the Indo
      Aryan language family. The dyadic Y-chromosome composition of Tibeto-Burman
      speakers of India, however, can be attributed to a recent demographic process,
      which appears to have absorbed and overlain populations who previously spoke
      Austro-Asiatic languages.

PMID- 16415162
TI  - Variations in the association of papillomavirus E2 proteins with mitotic
      chromosomes.
AB  - The E2 protein segregates episomal bovine papillomavirus (BPV) genomes to
      daughter cells by tethering them to mitotic chromosomes, thus ensuring equal
      distribution and retention of viral DNA. To date, only the BPV1 E2 protein has
      been shown to bind to mitotic chromosomes. We assessed the localization of 13
      different animal and human E2 proteins from seven papillomavirus genera, and we
      show that most of them are stably bound to chromosomes throughout mitosis.
      Furthermore, in contrast to the random association of BPV1 E2 with mitotic
      chromosomes, several of these proteins appear to bind to more specific regions of
      mitotic chromosomes. Using human papillomavirus (HPV) type 8 E2, we show that
      this region is adjacent to centromeres/kinetochores. Therefore, E2 proteins from
      both HPV and animal papillomavirus bind to mitotic chromosomes, and there are
      variations in the specificity of this binding. Only the alpha-papillomavirus E2
      proteins do not stably associate with mitotic chromatin throughout mitosis. These
      proteins closely associate with prophase chromosomes and bind to chromosomes in
      telophase but not in metaphase. However, extraction of mitotic cells before
      fixation results in alpha-E2 proteins binding to the pericentromeric region of
      metaphase chromosomes, as observed for HPV8 E2. We postulate that this is the
      authentic target of these E2 proteins but that additional factors or a
      specialized cellular environment is required to stabilize this association. Thus,
      E2-mediated tethering of viral genomes to mitotic chromosomes is a common
      strategy of papillomaviruses, but different viruses have evolved different
      variations of this theme.

PMID- 16415163
TI  - Recent behavioral history modifies coupling between cell activity and Arc gene
      transcription in hippocampal CA1 neurons.
AB  - The ability of neurons to alter their transcriptional programs in response to
      synaptic input is of fundamental importance to the neuroplastic mechanisms
      underlying learning and memory. Because of technical limitations of conventional
      gene detection methods, the current view of activity-dependent neural
      transcription derives from experiments in which neurons are assumed quiescent
      until a signaling stimulus is given. The present study was designed to move
      beyond this static model by examining how earlier episodes of neural activity
      influence transcription of the immediate-early gene Arc. Using a sensitive FISH
      method that detects primary transcript at genomic alleles, the proportion of
      hippocampal CA1 neurons that activate transcription of Arc RNA was constant at
      approximately 40% in response to both a single novel exploration session and
      daily sessions repeated over 9 days. This proportion is similar to the percentage
      of active neurons defined electrophysiologically. However, this close
      correspondence was disrupted in rats exposed briefly, but repeatedly, to the same
      environment within a single day. Arc transcription in CA1 neurons declined
      dramatically after as few as four 5-min sessions, despite stable
      electrophysiological activity during all sessions. Additional experiments
      indicate that the decrement in Arc transcription occurred at the cellular, rather
      than synaptic level, and was not simply linked to habituation to novelty. Thus,
      the neural genomic response is governed by recent, but not remote, cell firing
      history in the behaving animal. This state-dependence of neuronal transcriptional
      coupling provides a mechanism of metaplasticity and may regulate capacity for
      synaptic modification in neural networks.

PMID- 16415164
TI  - Cellular identification of water gustatory receptor neurons and their central
      projection pattern in Drosophila.
AB  - Water perception is important for insects, because they are particularly
      vulnerable to water loss because their body size is small. In Drosophila,
      gustatory receptor neurons are located at the base of the taste sensilla on the
      labellum, tarsi, and wing margins. One of the gustatory receptor neurons in
      typical sensilla is known to respond to water. To reveal the neural mechanisms of
      water perception in Drosophila, it is necessary to identify water receptor
      neurons and their projection patterns. We used a Gal4 enhancer trap strain in
      which GAL4 is expressed in a single gustatory receptor neuron in each sensillum
      on the labellum. We investigated the function of these neurons by expressing the
      upstream activating sequence transgenes, shibire(ts1), tetanus toxin light chain,
      or diphtheria toxin A chain. Results from the proboscis extension reflex test and
      electrophysiological recordings indicated that the GAL4-expressing neurons
      respond to water. We show here that the water receptor neurons project to a
      specific region in the subesophageal ganglion, thus revealing the water taste
      sensory map in Drosophila.

PMID- 16415165
TI  - Effector-phase tolerance: another mechanism of how cancer escapes antitumor
      immune response.
AB  - Growth of cancer in rodent models and in patients elicits immune responses
      directed toward various antigens expressed by the transformed cell. Clearly
      though, as most tumors grow, unmanipulated antitumor immune responses are
      incapable of eliminating cancer. Over the past approximately 15 years, antitumor
      immunoglobulin and T cells have been used to identify tumor antigens, which in
      turn, have served as the basis for therapeutic vaccine trials. However,
      experimental cancer vaccines, although in some patients result in elimination of
      large tumor burdens, have a low frequency of long-term cancer remission in most
      patients, ca. <5%. Therefore, as tumors express antigens that distinguish
      themselves from nontransformed cells in immunological terms (i.e., elicit immune
      responses to growth of primary tumor and can target tumor cells in vivo), and
      tumor vaccines prime unsuccessful antitumor immune responses in patients, it is
      likely that growth of cancer induces immune tolerance to tumor cells. Although
      there are several types of T cell tolerance, mature, antigen-specific CD8+ T
      cells isolated from tumors are lytic-defective, implying that the tumor
      microenvironment inactivates the antitumor effector phase. The nature of the
      functional local tolerance to antitumor immune response is the subject of this
      review.

PMID- 16415166
TI  - Mycobacterium paratuberculosis, Mycobacterium smegmatis, and lipopolysaccharide
      induce different transcriptional and post-transcriptional regulation of the IRG1
      gene in murine macrophages.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic enteritis
      in ruminants. In addition, MAP is presently the most favored pathogen linked to
      Crohn's disease. In this study, we were interested in dissecting the molecular
      mechanisms of macrophage activation or deactivation after infection with MAP. By
      subtractive hybridization of cDNAs, we identified the immune-responsive gene 1
      (IRG1), which was expressed substantially higher in lipopolysaccharide (LPS)
      stimulated than in MAP-infected murine macrophage cell lines. A nuclear run-on
      transcription assay revealed that the IRG1 gene was activated transcriptionally
      in LPS-stimulated and MAP-infected macrophages with higher expression in LPS
      stimulated cells. Analysis of post-transcriptional regulation demonstrated that
      IRG1 mRNA stability was increased in LPS-stimulated but not in MAP-infected
      macrophages. Furthermore, IRG1 gene expression of macrophages infected with the
      nonpathogenic Mycobacterium smegmatis differed from those of LPS-stimulated and
      MAP-infected macrophages. At 2 h postinfection, M. smegmatis-induced IRG1 gene
      expression was as low as in MAP-infected, and 8 h postinfection, it increased
      nearly to the level in LPS-stimulated macrophages. Transient transfection
      experiments revealed similar IRG1 promoter activities in MAP- and M. smegmatis
      infected cells. Northern analysis demonstrated increased IRG1 mRNA stability in
      M. smegmatis-infected macrophages. IRG1 mRNA stabilization was p38 mitogen
      activated protein kinase-independent. Inhibition of protein synthesis revealed
      that constitutively expressed factors seemed to be responsible for IRG1 mRNA
      destabilization. Thus, our data demonstrate that transcriptional and post
      transcriptional mechanisms are responsible for a differential IRG1 gene
      expression in murine macrophages treated with LPS, MAP, and M. smegmatis.

PMID- 16415167
TI  - CD13 in cell adhesion: aminopeptidase N (CD13) mediates homotypic aggregation of
      monocytic cells.
AB  - Homotypic aggregation (HA) of cells plays key roles in physiological and
      pathological processes, such as embryogenesis, immune responses, angiogenesis,
      tumor cell invasion, and metastasis. Aminopeptidase N (CD13) has been implicated
      in most of these phenomena, although its participation has been attributed to its
      enzymatic activity, while its role as an adhesion molecule has been almost
      unexplored. Here, we show that certain anti-CD13 monoclonal antibodies induce HA
      of monocytic U-937 cells, independently of their effect on enzymatic activity.
      The phenomenon is related to binding to a specific site on the CD13 molecule and
      is independent of integrins. It is abrogated by low temperature, by the
      glycolysis inhibitor 2-deoxyglucose, and by inhibitors of tyrosine and mitogen
      activated protein kinases. The inhibitor of microtubule polymerization colchicine
      has a synergistic effect on CD13-mediated aggregation, suggesting an inhibitory
      role of microtubules in this process. Finally, during HA, CD13 actively
      redistributes to the zones of cell-cell contact, as determined by live cell
      imaging studies, demonstrating a direct role of CD13 in the adhesion phenomenon.
      Together, these data show for the first time the participation of CD13 in
      monocytic cell adhesion.

PMID- 16415168
TI  - Characterizing the circulating, gliadin-specific CD4+ memory T cells in patients
      with celiac disease: linkage between memory function, gut homing and Th1
      polarization.
AB  - Celiac disease (CD) is a chronic, immune-mediated disorder of the gut, driven by
      T cells reacting locally to a distinct antigen, gliadin. Thus, CD offers the
      opportunity to study the T cell memory response to gliadin and whether gut
      tropism and T helper cell type 1 (Th1) polarization, which characterize the
      effector phase, are preserved in the memory progeny. It is notable that previous
      studies yielded conflicting results as to the presence of gliadin-specific memory
      CD4+ T cells in the peripheral blood of CD patients. However, we used a different
      and highly sensitive approach based on fluorescein-derived label dilution,
      whereby the memory cells are identified operationally by their greater capacity
      to proliferate upon re-encounter with antigen. Thus, using flow cytometry, we
      could resolve multiple successive generations as well as immunophenotype the
      dividing cells. Here, we show that the peripheral blood lymphocyte of some CD
      patients on a gliadin-free diet, but not healthy donors, contains a detectable
      population of CD4+ memory T cells specific for deamidated gliadin. Moreover,
      these gliadin-specific memory T cells are marked by a distinctive phenotype: They
      express high levels of the gut-homing beta7 integrins and primarily produce
      interferon-gamma and tumor necrosis factor alpha. We conclude that memory for
      gliadin-derived antigens within the circulating CD4+ T cells is linked with gut
      tropism as well as Th1 polarization.

PMID- 16415169
TI  - The immunoregulatory effects of gangliosides involve immune deviation favoring
      type-2 T cell responses.
AB  - Gangliosides, sialic acid-containing glycosphingolipids present in most cell
      membranes, are thought to participate in the maintenance of immune privilege and
      tumor-induced immunosuppression. However, the mechanisms responsible for their
      immunomodulatory activity remain poorly understood. The purpose of this study was
      to investigate whether gangliosides are able to modulate the balance of type
      1/type-2 T cell responses and to characterize the cellular mechanisms involved.
      The effects of different gangliosides on anti-CD3-stimulated murine splenocytes
      and purified T cells were studied. The presence of gangliosides during T cell
      activation reduced the expression of interferon-gamma (IFN-gamma) and enhanced
      that of interleukin (IL)-4, suggesting a shift toward a type-2 response.
      Intracellular cytokine staining demonstrated that gangliosides inhibited IFN
      gamma production in CD4+, CD8+, and natural killer (NK)1.1+ cell populations and
      enhanced IL-4 in CD4+ T cells. The ganglioside-mediated enhancement in IL-4
      production was independent of changes in endogenous IFN-gamma, did not occur with
      cells from CD1d-deficient mice, and was partially inhibited by anti-CD1d
      antibodies. The inhibitory effects on IFN-gamma were independent of endogenous IL
      4 or the presence of NKT cells and were unaffected by anti-CD1d antibodies. These
      results suggest that gangliosides may modify the immunological environment by
      promoting immune deviation in favor of type-2 T cell responses.

PMID- 16415170
TI  - H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated
      stimulations, and resistance to activation-induced apoptosis during T cell
      response to mycobacterial antigens.
AB  - Genetic variation in the major histocompatibility complex (MHC) influences
      susceptibility and immune responses to Mycobacterium tuberculosis in mice and
      humans, but connections among the severity of tuberculosis (TB), dynamic changes
      in T cell responses to mycobacteria, and MHC genetic polymorphisms are poorly
      characterized. The overall effect of the MHC genes on TB susceptibility and
      cellular responses to mycobacteria is moderate; thus, such studies provide
      reliable results only if congenic mouse strains bearing a variety of H2
      haplotypes on an identical genetic background are analyzed. Using a panel of H2
      congenic strains on the B10 background, we demonstrate that T cells from mice of
      three different strains, which are resistant to TB infection, readily respond by
      proliferation to repeated stimulations with mycobacterial sonicate, whereas T
      cells from three susceptible mouse strains die after the second stimulation with
      antigen. This difference is specific, as T cells from TB-susceptible and 
      resistant mouse strains do not differ in response to irrelevant antigens. The
      CD4/CD8 ratio in immune lymph nodes correlates strongly and inversely with TB
      susceptibility, being significantly lower in resistant mice as a result of an
      increased content of CD8+ cells. These differences between the two sets of mouse
      strains correlate with an elevated level of activation-induced T cell apoptosis
      in TB-susceptible mice and a higher proportion of activated CD44+ CD62 ligand- T
      cells in TB-resistant mice. These results may shed some light on the nature of
      the cellular basis of MHC-linked differences in susceptibility to TB.

PMID- 16415171
TI  - Platelet binding to monocytes increases the adhesive properties of monocytes by
      up-regulating the expression and functionality of beta1 and beta2 integrins.
AB  - Human monocytes adhere to activated platelets, resulting in the formation of
      platelet-monocyte complexes (PMC). Complex formation depends on the interaction
      between platelet-displayed P-selectin and the specific ligand for P-selectin on
      leukocytes, P-selectin glycoprotein ligand-1 (PSGL-1). We have recently shown
      that monocytes within PMC have increased adhesive capacity to the activated
      endothelium. To better understand the effect of platelet binding on the capacity
      of monocytes to adhere to activated endothelium, the P-selectin-PSGL-1
      interaction-induced changes in integrin functionality were studied. The binding
      of platelets to monocytes via P-selectin-PSGL-1 interactions was shown to
      increase expression and activity of alpha4beta1 and alphaMbeta2integrin, with a
      concomitant decrease in L-selectin expression. Furthermore, the binding of
      platelets to monocytes resulted in increased monocyte adhesion to intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1, and fibronectin. Platelet
      binding was also responsible for an increase in monocyte transendothelial
      migration. Similar effects were observed after engagement of PSGL-1 with specific
      antibodies or with P-selectin immunoglobulin protein. Our data suggest that
      platelets, by binding via P-selectin to PSGL-1 on monocytes, induce up-regulation
      and activation of beta1 and beta2integrins and increased adhesion of monocytes to
      activated endothelium. Hence, monocytes within PMC are in a higher state of
      activation and may have, therefore, an increased atherogenic capacity.

PMID- 16415173
TI  - The effect of PGG-beta-glucan on neutrophil chemotaxis in vivo.
AB  - The beta-glucans are long-chain polymers of glucose in beta-(1,3)(1,6) linkages,
      which comprise the fungal cell wall and stimulate cells of the innate immune
      system. Previous in vitro studies have shown the ability of beta-glucan to
      increase the chemotactic capacity of human neutrophils. The current study
      examined an in vivo correlate of that observation by testing the hypothesis that
      systemic beta-glucan treatment would result in enhanced migration of neutrophils
      into a site of inflammation and improve antimicrobial function. A model of acute
      inflammation was used in which polyvinyl alcohol sponges were implanted
      subcutaneously into the dorsum of rats. Animals treated with beta-glucan showed a
      66 +/- 6% and 186 +/- 42% increase in wound cell number recovered 6 and 18 h
      postwounding, respectively. Increased migration did not correlate with increased
      chemoattractant content of wound fluid, alterations in neutrophil-induced loss of
      endothelial barrier function, or changes in neutrophil adhesion to endothelial
      cells. Systemic administration of SB203580 abrogated the enhanced migration by
      beta-glucan without altering normal cellular entry into the wound. Studies also
      showed a priming effect for chemotaxis and respiratory burst in circulating
      neutrophils isolated from beta-glucan-treated animals. Heightened neutrophil
      function took place without cytokine elicitation. Furthermore, beta-glucan
      treatment resulted in a 169 +/- 28% increase in neutrophil number and a 60 +/- 9%
      decrease in bacterial load in the bronchoalveolar lavage fluid of Escherichia
      coli pneumonic animals. Taken together, these findings demonstrate that beta
      glucan directly affects the chemotactic capacity of circulating neutrophils
      through a p38 mitogen-activated protein kinase-dependent mechanism and
      potentiates antimicrobial host defense.

PMID- 16415172
TI  - The Kupffer cell protects against acute lung injury in a rat peritonitis model:
      role of IL-10.
AB  - The possibility that Kupffer cells (KCs) play key beneficial and deleterious
      roles in multiple organ injury in sepsis has been discussed. The role of KCs in
      lung injury in a rat peritonitis model was investigated. Specifically, the
      involvement of interleukin (IL)-10, which has anti-inflammatory effects, was
      examined. Rats were given saline or gadolinium chloride (GdCl3), a KC toxicant,
      24 h before cecal ligation and puncture (CLP). Survival was assessed for 7 days
      after CLP. The liver, lung, and serum were harvested, and the expression of
      cytokines was assessed. Macrophages were isolated from each organ after CLP, and
      the mRNA expression of inflammatory mediators was assessed. GdCl3 treatment
      increased lung injury and mortality. Plasma endotoxin levels were significantly
      greater, whereas serum IL-10 levels were lower in the GdCl3 than in the control
      group after CLP. IL-10 levels were significantly greater in the aorta than the
      hepatic vein. The mRNA expression of IL-10 was less in KCs from the GdCl3 than
      the control group. In the liver, the expression of IL-10 increased rapidly and
      continuously, up to 9 h in the control group, but values were significantly lower
      in the GdCl3 group. Rabbit anti-rat IL-10 antibodies were injected just after CLP
      to investigate the effects of immunoneutralization of endogenously produced IL
      10. In the antibody-treated group, lung injury and mortality increased compared
      with animals treated with rabbit immunoglobulin G. Taken together, these results
      indicate that KCs play a protective role in lung injury in sepsis by production
      of IL-10.

PMID- 16415174
TI  - MCP-1/CCR2-dependent loop for fibrogenesis in human peripheral CD14-positive
      monocytes.
AB  - Monocyte/macrophage (Momicron) migration to sites of inflammation is a
      prerequisite cause of organ fibrosis. The recruitment and activation of Mo are
      regulated by C-C chemokines, especially monocyte chemoattractant protein-1 [(MCP
      1)/CC chemokine ligand 2], which interacts with CC chemokine receptor 2 (CCR2).
      However, the mechanisms leading to fibrosis via MCP-1/CCR2 signaling in Mo remain
      to be investigated. The effect of MCP-1 on the expression of MCP-1, CCR2,
      transforming growth factor-beta1 (TGF-beta1), and type I collagen in circulating
      human CD14-positive Mo was investigated. In addition, the impact of MCP-1
      specific or TGF-beta1-specific antisense (AS) phosphorothioate
      oligodeoxynucleotides (ODN) was examined to explore the involvement of
      autocrine/paracrine production of MCP-1 and TGF-beta1 by human CD14-positive Mo.
      Furthermore, specific CCR2 inhibitors were applied to examine the involvement of
      CCR2 signaling for the promotion of a fibrogenic response. The stimulation of Mo
      with MCP-1 increased mRNA levels of TGF-beta1 and a pro-alpha1 chain of type I
      collagen (COL1A1) as well as protein synthesis. Similarly, the expression of MCP
      1 and CCR2 was enhanced by the stimulation with MCP-1 in dose- and time-dependent
      manners. This positive loop via MCP-1 was reduced by pretreatment with MCP-1
      specific AS-ODN. It was also noted that pretreatment with TGF-beta1-specific AS
      ODN partially reduced COL1A1 mRNA levels. Finally, transcripts of these molecules
      were suppressed by pretreatment with specific CCR2 inhibitors. The present study
      demonstrated that human peripheral CD14-positive Mo contribute directly to
      fibrogenesis by a MCP-1/CCR2-dependent amplification loop. These data suggest
      that fibrogenic processes in Mo regulated by MCP-1/CCR2 may be novel, therapeutic
      targets for combating organ fibrosis.

PMID- 16415175
TI  - High throughput SNP and expression analyses of candidate genes for non-syndromic
      oral clefts.
AB  - BACKGROUND: Recent work suggests that multiple genes and several environmental
      risk factors influence risk for non-syndromic oral clefts, one of the most common
      birth defects in humans. Advances in high-throughput genotyping technology now
      make it possible to test multiple markers in many candidate genes simultaneously.
      METHODS: We present findings from family based association tests of single
      nucleotide polymorphism (SNP) markers in 64 candidate genes genotyped using the
      BeadArray approach in 58 case-parent trios from Maryland (USA) to illustrate how
      multiple markers in multiple genes can be analysed. To assess whether these genes
      were expressed in human craniofacial structures relevant to palate and lip
      development, we also analysed data from the Craniofacial and Oral Gene Expression
      Network (COGENE) consortium, and searched public databases for expression
      profiles of these genes. RESULTS: Thirteen candidate genes showed significant
      evidence of linkage in the presence of disequilibrium, and ten of these were
      found to be expressed in relevant embryonic tissues: SP100, MLPH, HDAC4, LEF1,
      C6orf105, CD44, ALX4, ZNF202, CRHR1, and MAPT. Three other genes showing
      statistical evidence (ADH1C, SCN3B, and IMP5) were not expressed in the embryonic
      tissues examined here. CONCLUSIONS: This approach demonstrates how statistical
      evidence on large numbers of SNP markers typed in case-parent trios can be
      combined with expression data to identify candidate genes for complex disorders.
      Many of the genes reported here have not been previously studied as candidates
      for oral clefts and warrant further investigation.

PMID- 16415176
TI  - Adenylyl cyclase superactivation induced by long-term treatment with opioid
      agonist is dependent on receptor localized within lipid rafts and is independent
      of receptor internalization.
AB  - Long-term opioid agonist treatment results in adenylyl cyclase superactivation. A
      recent "RAVE" theory implicates a direct correlation between the ability of
      agonist to induce receptor internalization and the magnitude of adenylyl cyclase
      superactivation. We decided to test such a theory by examining the adenylyl
      cyclase superactivation after long-term activation of mu-opioid receptor (MOR) in
      an EcR293 cell model. We examined the magnitudes of adenylyl cyclase
      superactivation in the presence of naloxone after long-term treatment with
      morphine, etorphine, and methadone, three agonists reported to have differential
      activities in promoting MOR internalization. It can be shown that the magnitudes
      of adenylyl cyclase superactivation after treating with these three agonists,
      although different, were dependent on MOR density. Blunting MOR internalization
      with the dominant-negative mutant of dynamin, K44E, did not alter the magnitude
      of either morphine- or etorphine-induced adenylyl cyclase superactivation. In the
      presence of diprenorphine, the magnitude of adenylyl cyclase superactivation
      after etorphine treatment was identical to that observed with morphine. It could
      be demonstrated further that adenylyl cyclase superactivation is dependent on the
      cell surface-located MOR. Sucrose gradient fractionation demonstrated the
      colocalization of MOR and adenylyl cyclase V/VI with caveolin-1, a marker for
      lipid rafts. After long-term agonist treatment, the majority of MOR remained at
      the lipid rafts. Methyl-beta-cyclodextrin (MbetaCD) completely blunted the
      adenylyl cyclase superactivation and agonist-induced receptor internalization.
      These MbetaCD actions were reversed by incubating the cells with cholesterol.
      Thus, the adenylyl cyclase superactivation is not dependent on agonist-induced
      receptor internalization. Rather, the location of MOR at lipid rafts is an
      absolute requirement for the observed adenylyl cyclase superactivation.

PMID- 16415177
TI  - Discovery of naturally occurring splice variants of the rat histamine H3 receptor
      that act as dominant-negative isoforms.
AB  - We described previously the cDNA cloning of three functional rat histamine H3
      receptor (rH3R) isoforms as well as the differential brain expression patterns of
      their corresponding mRNAs and signaling properties of the resulting rH3A, rH3B,
      and rH3C receptor isoforms (Mol Pharmacol 59:1-8). In the current report, we
      describe the cDNA cloning, mRNA localization in the rat central nervous system,
      and pharmacological characterization of three additional rH3R splice variants
      (rH3D, rH3E, and rH3F) that differ from the previously published isoforms in that
      they result from an additional alternative-splicing event. These new H3R isoforms
      lack the seventh transmembrane (TM) helix and contain an alternative, putatively
      extracellular, C terminus (6TM-rH3 isoforms). After heterologous expression in
      COS-7 cells, radioligand binding or functional responses upon the application of
      various H3R ligands could not be detected for the 6TM-rH3 isoforms. In contrast
      to the rH3A receptor (rH3AR), detection of the rH3D isoform using hemagglutinin
      antibodies revealed that the rH3D isoform remains mainly intracellular. The
      expression of the rH3D-F splice variants, however, modulates the cell surface
      expression-levels and subsequent functional responses of the 7TM H3R isoforms.
      Coexpression of the rH3AR and the rH3D isoforms resulted in the intracellular
      retention of the rH3AR and reduced rH3AR functionality. Finally, we show that in
      rat brain, the H3R mRNA expression levels are modulated upon treatment with the
      convulsant pentylenetetrazole, suggesting that the rH3R isoforms described herein
      thus represent a novel physiological mechanism for controlling the activity of
      the histaminergic system.

PMID- 16415178
TI  - The microtubule binding drug laulimalide inhibits vascular endothelial growth
      factor-induced human endothelial cell migration and is synergistic when combined
      with docetaxel (taxotere).
AB  - Laulimalide, a natural product from marine sponges, is a microtubule-stabilizing
      agent that binds to tubulin at a site distinct from that of the taxoids. In the
      present study, we found that laulimalide inhibited human umbilical vein
      endothelial cell (HUVEC) tubule formation and vascular endothelial growth factor
      (VEGF)-induced HUVEC migration, key components of the angiogenic process. These
      occurred at concentrations substantially lower than that which inhibited HUVEC
      proliferation. When combined, laulimalide and docetaxel (Taxotere)
      synergistically inhibited migration and tubule formation, but their combined
      effect on proliferation was antagonistic. Possible mechanism(s) by which
      laulimalide inhibited VEGF-induced HUVEC migration were explored. Similar to
      docetaxel, laulimalide had no effect on the VEGF-induced tyrosine phosphorylation
      of the VEGF receptor Flk-1/KDR (VEGFR-2). Low concentrations of laulimalide
      substantially blocked subsequent VEGFR-2 downstream events, as did docetaxel,
      including the phosphorylation of the Tyr397 and Tyr407 residues of focal adhesion
      kinase (FAK), the association of VEGFR-2 with FAK and Hsp90, and the Tyr31
      phosphorylation of paxillin. Laulimalide inhibited integrin activation; however,
      compared with docetaxel, it had a weaker inhibitory effect on the VEGF-induced
      association of VEGFR-2 with the alpha5beta1 integrin. Compared with docetaxel,
      laulimalide more potently caused a reduction in the constitutive levels (i.e., in
      the absence of VEGF) of phosphorylated paxillin and more potently inhibited the
      association of RhoA with the alpha5beta1 integrin. In conclusion, although both
      docetaxel and laulimalide inhibited integrin-associated signaling pathways that
      mediated VEGF-induced cell migration, their actions on the signaling cascade
      seemed not to be identical. These complementary actions could account for their
      synergistic effects on HUVEC.

PMID- 16415179
TI  - p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone
      interaction.
AB  - The Mi-2/NuRD complex is a multi-subunit protein complex with enzymatic
      activities involving chromatin remodeling and histone deacetylation. Targeting of
      Mi-2/NuRD to methylated CpG sequences mediates gene repression. The function of
      p66alpha and of p66beta within the multiple subunits has not been addressed.
      Here, we analyzed the in vivo function and binding of both p66-paralogs. Both
      factors function in synergy, since knocking-down p66alpha affects the repressive
      function of p66beta and vice versa. Both proteins interact with MBD2 functionally
      and biochemically. Mutation of a single amino acid of p66alpha abolishes in vivo
      binding to MBD2 and interferes with MBD2-mediated repression. This loss of
      binding results in a diffuse nuclear localization in contrast to wild-type
      p66alpha that shows a speckled nuclear distribution. Furthermore, wild-type
      subnuclear distribution of p66alpha and p66beta depends on the presence of MBD2.
      Both proteins interact with the tails of all octamer histones in vitro, and
      acetylation of histone tails interferes with p66 binding. The conserved region 2
      of p66alpha is required for histone tail interaction as well as for wild-type
      subnuclear distribution. These results suggest a two-interaction forward feedback
      binding mode, with a stable chromatin association only after deacetylation of the
      histones has occurred.

PMID- 16415183
TI  - Stamps in cardiology. Millennium stamps.

PMID- 16415180
TI  - Poleta, Polzeta and Rev1 together are required for G to T transversion mutations
      induced by the (+)- and (-)-trans-anti-BPDE-N2-dG DNA adducts in yeast cells.
AB  - Benzo[a]pyrene is an important environmental mutagen and carcinogen. Its
      metabolism in cells yields the mutagenic, key ultimate carcinogen 7R,8S,9S,10R
      anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, (+)-anti-BPDE, which reacts via
      its 10-position with N2-dG in DNA to form the adduct (+)-trans-anti-BPDE-N2-dG.
      To gain molecular insights into BPDE-induced mutagenesis, we examined in vivo
      translesion synthesis and mutagenesis in yeast cells of a site-specific 10S (+)
      trans-anti-BPDE-N(2)-dG adduct and the stereoisomeric 10R (-)-trans-anti-BPDE-N2
      dG adduct. In wild-type cells, bypass products consisted of 76% C, 14% A and 7% G
      insertions opposite (+)-trans-anti-BPDE-N2-dG; and 89% C, 4% A and 4% G
      insertions opposite (-)-trans-anti-BPDE-N2-dG. Translesion synthesis was reduced
      by approximately 26-37% in rad30 mutant cells lacking Poleta, but more deficient
      in rev1 and almost totally deficient in rev3 (lacking Polzeta) mutants. C
      insertion opposite the lesion was reduced by approximately 24-33% in rad30 mutant
      cells, further reduced in rev1 mutant, and mostly disappeared in the rev3 mutant
      strain. The insertion of A was largely abolished in cells lacking either Poleta,
      Polzeta or Rev1. The insertion of G was not detected in either rev1 or rev3
      mutant cells. The rad30 rev3 double mutant exhibited a similar phenotype as the
      single rev3 mutant with respect to translesion synthesis and mutagenesis. These
      results show that while the Polzeta pathway is generally required for translesion
      synthesis and mutagenesis of the (+)- and (-)-trans-anti-BPDE-N2-dG DNA adducts,
      Poleta, Polzeta and Rev1 together are required for G-->T transversion mutations,
      a major type of mutagenesis induced by these lesions. Based on biochemical and
      genetic results, we present mechanistic models of translesion synthesis of these
      two DNA adducts, involving both the one-polymerase one-step and two-polymerase
      two-step models.

PMID- 16415182
TI  - Sex differences and cardiovascular risk.
AB  - Cardiovascular risk factors such as diabetes confer differing degrees of risk in
      men and women.

PMID- 16415184
TI  - B-type natriuretic peptide: a role in selection and follow up of the implantable
      cardioverter-defibrillator patient?
AB  - B-type natriuretic peptide may have a role in predicting the risk of ICD therapy,
      identifying patients with deteriorating clinical status and allowing them to be
      selected for more detailed medical review and, if necessary, drug treatment.

PMID- 16415185
TI  - Images in cardiology. Left ventricular pseudoaneurysm complicating acute
      myocardial infarction: improved diagnosis by real time three dimensional
      echocardiography.

PMID- 16415186
TI  - Images in cardiology. Use of magnetic resonance imaging in the diagnosis of
      aneurysm of fossa ovalis.

PMID- 16415187
TI  - Images in cardiology. Aberrant right coronary artery collaterals to pulmonary
      vascular bed.

PMID- 16415188
TI  - Images in cardiology. Pseudo-supraventricular tachycardia.

PMID- 16415189
TI  - Images in cardiology. False positive massive pulmonary embolus.

PMID- 16415190
TI  - Images in cardiology. Myocardial calcification: a rare cause of diastolic
      dysfunction.

PMID- 16415191
TI  - Images in cardiology. Abnormal left atrial membranous structure in transthoracic
      echocardiography caused by external compression from a large bronchogenic cyst.

PMID- 16415192
TI  - Images in cardiology. Left atrial obliteration after coronary artery perforation.

PMID- 16415193
TI  - Novel anti-inflammatory effect of statins: reduction of CD4+CD28null T lymphocyte
      frequency in patients with unstable angina.

PMID- 16415194
TI  - Randomised comparison of manual compression repair versus ultrasound guided
      compression repair of postcatheterisation femoral pseudoaneurysms.

PMID- 16415195
TI  - Progenitor cell mobilisation in patients with acute and chronic coronary artery
      disease.

PMID- 16415196
TI  - Relation between severity of left ventricular systolic dysfunction and
      repolarisation abnormalities on the surface ECG: a report from the Euro heart
      failure survey.

PMID- 16415197
TI  - Triggering of acute coronary syndromes after a chemical plant explosion.

PMID- 16415198
TI  - Fasting hypertriglyceridaemia increases carotid intima-media thickness and
      impairs coronary microvascular functions in non-obese middle aged women but not
      in men.

PMID- 16415199
TI  - Impact of cinematic viewing on endothelial function.

PMID- 16415200
TI  - Images in cardiology. Intramyocardial bridging of the left anterior descending
      artery: appearance of arterial compression on ECG gated multidetector row CT.

PMID- 16415201
TI  - Magnetic resonance imaging of the brain and haematological profile in adult
      cyanotic congenital heart disease without stroke.

PMID- 16415202
TI  - Images in cardiology. Fistulas from all three major coronaries arteries to the
      left ventricle.

PMID- 16415203
TI  - Catheter and surgical ablation of atrial fibrillation.

PMID- 16415204
TI  - Mitral valve repair: better than replacement.

PMID- 16415205
TI  - Cardiac sarcoidosis.

PMID- 16415206
TI  - Involvement of a glycerol-3-phosphate dehydrogenase in modulating the NADH/NAD+
      ratio provides evidence of a mitochondrial glycerol-3-phosphate shuttle in
      Arabidopsis.
AB  - A mitochondrial glycerol-3-phosphate (G-3-P) shuttle that channels cytosolic
      reducing equivalent to mitochondria for respiration through oxidoreduction of G-3
      P has been extensively studied in yeast and animal systems. Here, we report
      evidence for the operation of such a shuttle in Arabidopsis thaliana. We studied
      Arabidopsis mutants defective in a cytosolic G-3-P dehydrogenase, GPDHc1, which,
      based on models described for other systems, functions as the cytosolic component
      of a G-3-P shuttle. We found that the gpdhc1 T-DNA insertional mutants exhibited
      increased NADH/NAD+ ratios compared with wild-type plants under standard growth
      conditions, as well as impaired adjustment of NADH/NAD+ ratios under stress
      simulated by abscisic acid treatment. The altered redox state of the NAD(H) pool
      was correlated with shifts in the profiles of metabolites concerning
      intracellular redox exchange. The impairment in maintaining cellular redox
      homeostasis was manifest by a higher steady state level of reactive oxygen
      species under standard growth conditions and by a significantly augmented
      hydrogen peroxide production under stress. Loss of GPDHc1 affected mitochondrial
      respiration, particularly through a diminished capacity of the alternative
      oxidase respiration pathway. We propose a model that outlines potential
      involvements of a mitochondrial G-3-P shuttle in plant cells for redox
      homeostasis.

PMID- 16415208
TI  - Members of a novel class of Arabidopsis Rho guanine nucleotide exchange factors
      control Rho GTPase-dependent polar growth.
AB  - Rho family small GTPases are signaling switches controlling many eukaryotic
      cellular processes. Conversion from the GDP- to GTP-bound form is catalyzed by
      guanine nucleotide exchange factors (GEFs). Rho GEFs in animals fall into two
      structurally distinct classes containing DH and DOCKER catalytic domains. Using a
      plant Rho GTPase (ROP1) as bait in yeast two-hybrid screens, we identified a
      family of Rho GEFs, named RopGEFs. The Arabidopsis thaliana RopGEF family of 14
      members contains a conserved central domain, the domain of unknown function 315
      (DUF315), and variable N- and C-terminal regions. In vitro GEF assays show that
      DUF315 but not the full-length version of RopGEF1 has high GEF activity toward
      ROP1. Our data suggest that the variable regions of RopGEF1 are involved in
      regulation of RopGEF through an autoinhibitory mechanism. RopGEF1 overexpression
      in pollen tubes produced growth depolarization, as does a constitutively active
      ROP1 mutant. The RopGEF1 overexpression phenotype was suppressed by expression of
      a dominant-negative mutant of ROP1, probably by trapping RopGEF1. Deletion mutant
      analysis suggested a requirement of RopGEF activity for the function of RopGEF1
      in polar growth. Green fluorescent protein-tagged RopGEF1 was localized to the
      tip of pollen tubes where ROP1 is activated. These results provide strong
      evidence that RopGEF1 activates ROP1 in control of polar growth in pollen tubes.

PMID- 16415207
TI  - The A-type cyclin CYCA2;3 is a key regulator of ploidy levels in Arabidopsis
      endoreduplication.
AB  - Plant cells frequently undergo endoreduplication, a process in which chromosomal
      DNA is successively duplicated in the absence of mitosis. It has been proposed
      that endoreduplication is regulated at its entry by mitotic cyclin-dependent
      kinase activity. However, the regulatory mechanisms for its termination remain
      unclear, although plants tightly control the ploidy level in each cell type. In
      the process of searching for regulatory factors of endoreduplication, the
      promoter of an Arabidopsis thaliana cyclin A gene, CYCA2;3, was revealed to be
      active in developing trichomes during the termination period of endoreduplication
      as well as in proliferating tissues. Taking advantage of the situation that
      plants encode highly redundant cyclin A genes, we were able to perform functional
      dissection of CYCA2;3 using null mutant alleles. Null mutations of CYCA2;3
      semidominantly promoted endocycles and increased the ploidy levels achieved in
      mature organs, but they did not significantly affect the proportion of cells that
      underwent endoreduplication. Consistent with this result, expression of the
      CYCA2;3-green fluorescent protein fusion protein restrained endocycles in a dose
      dependent manner. Moreover, a mutation in the destruction box of CYCA2;3
      stabilized the fusion protein in the nuclei and enhanced the restraint. We
      conclude that CYCA2;3 negatively regulates endocycles and acts as a key regulator
      of ploidy levels in Arabidopsis endoreduplication.

PMID- 16415209
TI  - The epidermis-specific extracellular BODYGUARD controls cuticle development and
      morphogenesis in Arabidopsis.
AB  - The outermost epidermal cell wall is specialized to withstand pathogens and
      natural stresses, and lipid-based cuticular polymers are the major barrier
      against incursions. The Arabidopsis thaliana mutant bodyguard (bdg), which
      exhibits defects characteristic of the loss of cuticle structure not attributable
      to a lack of typical cutin monomers, unexpectedly accumulates significantly more
      cell wall-bound lipids and epicuticular waxes than wild-type plants. Pleiotropic
      effects of the bdg mutation on growth, viability, and cell differentiation are
      also observed. BDG encodes a member of the alpha/beta-hydrolase fold protein
      superfamily and is expressed exclusively in epidermal cells. Using Strep-tag
      epitope-tagged BDG for mutant complementation and immunolocalization, we show
      that BDG is a polarly localized protein that accumulates in the outermost cell
      wall in the epidermis. With regard to the appearance and structure of the
      cuticle, the phenotype conferred by bdg is reminiscent of that of transgenic
      Arabidopsis plants that express an extracellular fungal cutinase, suggesting that
      bdg may be incapable of completing the polymerization of carboxylic esters in the
      cuticular layer of the cell wall or the cuticle proper. We propose that BDG codes
      for an extracellular synthase responsible for the formation of cuticle. The
      alternative hypothesis proposes that BDG controls the
      proliferation/differentiation status of the epidermis via an unknown mechanism.

PMID- 16415210
TI  - Interaction between Arabidopsis Brca2 and its partners Rad51, Dmc1, and Dss1.
AB  - The Arabidopsis (Arabidopsis thaliana) orthologs of Brca2, a protein whose
      mutations are involved in breast cancer in humans, were previously shown to be
      essential at meiosis. In an attempt to better understand the Brca2-interacting
      properties, we examined four partners of the two isoforms of Brca2 identified in
      Arabidopsis (AtRad51, AtDmc1, and two AtDss1 isoforms). The two Brca2 and the two
      Dss1 isoforms are named AtBrca2(IV), AtBrca2(V), AtDss1(I), and AtDss1(V) after
      their chromosomal localization. We first show that both AtBrca2 proteins can
      interact with either AtRad51 or AtDmc1 in vitro, and that the N-terminal region
      of AtBrca2 is responsible for these interactions. More specifically, the BRC
      motifs (so called because iterated in the Brca2 protein) in Brca2 are involved in
      these interactions: BRC motif number 2 (BRC2) alone can interact with AtDmc1,
      whereas BRC motif number 4 (BRC4) recognizes AtRad51. The human Rad51 and Dmc1
      proteins themselves can interact with either the complete (HsRad51) or a shorter
      version of AtBrca2 (HsRad51 or HsDmc1) that comprises all four BRC motifs. We
      also identified two Arabidopsis isoforms of Dss1, another known partner of Brca2
      in other organisms. Although all four Brca2 and Dss1 proteins are much conserved,
      AtBrca2(IV) interacts with only one of these AtDss1 proteins, whereas AtBrca2(V)
      interacts with both of them. Finally, we show for the first time that an AtBrca2
      protein could bind two different partners at the same time: AtRad51 and
      AtDss1(I), or AtDmc1 and AtDss1(I).

PMID- 16415211
TI  - A central role for the nitrate transporter NRT2.1 in the integrated morphological
      and physiological responses of the root system to nitrogen limitation in
      Arabidopsis.
AB  - Up-regulation of the high-affinity transport system (HATS) for NO(3)(-) and
      stimulation of lateral root (LR) growth are two important adaptive responses of
      the root system to nitrogen limitation. Up-regulation of the NO(3)(-) HATS by
      nitrogen starvation is suppressed in the atnrt2.1-1 mutant of Arabidopsis
      (Arabidopsis thaliana), deleted for both NRT2.1 and NRT2.2 nitrate transporter
      genes. We then used this mutant to determine whether lack of HATS stimulation
      affected the response of the root system architecture (RSA) to low NO(3)(-)
      availability. In Wassilewskija (Ws) wild-type plants, transfer from high to low
      NO(3)(-) medium resulted in contrasting responses of RSA, depending on the level
      of nitrogen limitation. Moderate nitrogen limitation (transfer from 10 mm to 1 or
      0.5 mm NO(3)(-)) mostly led to an increase in the number of visible laterals,
      while severe nitrogen stress (transfer from 10 mm to 0.1 or 0.05 mm NO(3)(-))
      promoted mean LR length. The RSA response of the atnrt2.1-1 mutant to low NO(3)(
      ) was markedly different. After transfer from 10 to 0.5 mm NO(3)(-), the
      stimulated appearance of LRs was abolished in atnrt2.1-1 plants, whereas the
      increase in mean LR length was much more pronounced than in Ws. These
      modifications of RSA mimicked those of Ws plants subjected to severe nitrogen
      stress and could be fully explained by the lowered NO(3)(-) uptake measured in
      the mutant. This suggests that the uptake rate of NO(3)(-), rather than its
      external concentration, is the key factor triggering the observed changes in RSA.
      However, the mutation of NRT2.1 was also found to inhibit initiation of LR
      primordia in plants subjected to nitrogen limitation independently of the rate of
      NO(3)(-) uptake by the whole root system and even of the presence of added NO(3)(
      ) in the external medium. This indicates a direct stimulatory role for NRT2.1 in
      this particular step of LR development. Thus, it is concluded that NRT2.1 has a
      key dual function in coordinating root development with external NO(3)(-)
      availability, both indirectly through its role as a major NO(3)(-) uptake system
      that determines the nitrogen uptake-dependent RSA responses, and directly through
      a specific action on LR initiation under nitrogen-limited conditions.

PMID- 16415212
TI  - High-affinity nitrate transport in roots of Arabidopsis depends on expression of
      the NAR2-like gene AtNRT3.1.
AB  - The NAR2 protein of Chlamydomonas reinhardtii has no known transport activity yet
      it is required for high-affinity nitrate uptake. Arabidopsis (Arabidopsis
      thaliana) possesses two genes, AtNRT3.1 and AtNRT3.2, that are similar to the C.
      reinhardtii NAR2 gene. AtNRT3.1 accounts for greater than 99% of NRT3 mRNA and is
      induced 6-fold by nitrate. AtNRT3.2 was expressed constitutively at a very low
      level and did not compensate for the loss of AtNRT3.1 in two Atnrt3.1 mutants.
      Nitrate uptake by roots and nitrate induction of gene expression were analyzed in
      two T-DNA mutants, Atnrt3.1-1 and Atnrt3.1-2, disrupted in the AtNRT3.1 promoter
      and coding regions, respectively, in 5-week-old plants. Nitrate induction of the
      nitrate transporter genes AtNRT1.1 and AtNRT2.1 was reduced in Atnrt3.1 mutant
      plants, and this reduced expression was correlated with reduced nitrate
      concentrations in the tissues. Constitutive high-affinity influx was reduced by
      34% and 89%, respectively, in Atnrt3.1-1 and Atnrt3.1-2 mutant plants, while high
      affinity nitrate-inducible influx was reduced by 92% and 96%, respectively,
      following induction with 1 mm KNO(3) after 7 d of nitrogen deprivation. By
      contrast, low-affinity influx appeared to be unaffected. Thus, the constitutive
      high-affinity influx and nitrate-inducible high-affinity influx (but not the low
      affinity influx) of higher plant roots require a functional AtNRT3 (NAR2) gene.

PMID- 16415213
TI  - A segment of the apospory-specific genomic region is highly microsyntenic not
      only between the apomicts Pennisetum squamulatum and buffelgrass, but also with a
      rice chromosome 11 centromeric-proximal genomic region.
AB  - Bacterial artificial chromosome (BAC) clones from apomicts Pennisetum squamulatum
      and buffelgrass (Cenchrus ciliaris), isolated with the apospory-specific genomic
      region (ASGR) marker ugt197, were assembled into contigs that were extended by
      chromosome walking. Gene-like sequences from contigs were identified by shotgun
      sequencing and BLAST searches, and used to isolate orthologous rice contigs.
      Additional gene-like sequences in the apomicts' contigs were identified by
      bioinformatics using fully sequenced BACs from orthologous rice contigs as
      templates, as well as by interspecies, whole-contig cross-hybridizations.
      Hierarchical contig orthology was rapidly assessed by constructing detailed long
      range contig molecular maps showing the distribution of gene-like sequences and
      markers, and searching for microsyntenic patterns of sequence identity and
      spatial distribution within and across species contigs. We found microsynteny
      between P. squamulatum and buffelgrass contigs. Importantly, this approach also
      enabled us to isolate from within the rice (Oryza sativa) genome contig Rice A,
      which shows the highest microsynteny and is most orthologous to the ugt197
      containing C1C buffelgrass contig. Contig Rice A belongs to the rice genome
      database contig 77 (according to the current September 12, 2003, rice fingerprint
      contig build) that maps proximal to the chromosome 11 centromere, a feature that
      interestingly correlates with the mapping of ASGR-linked BACs proximal to the
      centromere or centromere-like sequences. Thus, relatedness between these two
      orthologous contigs is supported both by their molecular microstructure and by
      their centromeric-proximal location. Our discoveries promote the use of a
      microsynteny-based positional-cloning approach using the rice genome as a
      template to aid in constructing the ASGR toward the isolation of genes underlying
      apospory.

PMID- 16415214
TI  - Nickel deficiency disrupts metabolism of ureides, amino acids, and organic acids
      of young pecan foliage.
AB  - The existence of nickel (Ni) deficiency is becoming increasingly apparent in
      crops, especially for ureide-transporting woody perennials, but its physiological
      role is poorly understood. We evaluated the concentrations of ureides, amino
      acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni
      S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch).
      Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen
      metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle
      intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in
      accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but
      total ureides, urea concentration, and urease activity were reduced. Disruption
      of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine,
      valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids,
      and lower concentrations of histidine and glutamic acid. Ni deficiency also
      disrupted the citric acid cycle, the second stage of respiration, where Ni-D
      foliage contained very low levels of citrate compared to Ni-S foliage. Disruption
      of carbon metabolism was also via accumulation of lactic and oxalic acids. The
      results indicate that mouse-ear, a key morphological symptom, is likely linked to
      the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and
      margins of leaflets. Our results support the role of Ni as an essential plant
      nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan
      is evidence of the existence of unidentified physiological roles for Ni in pecan.

PMID- 16415216
TI  - An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for
      seedling establishment.
AB  - Once the plant coenzyme A (CoA) biosynthetic pathway has been elucidated by
      comparative genomics, it is feasible to analyze the physiological relevance of
      CoA biosynthesis in plant life. To this end, we have identified and characterized
      Arabidopsis (Arabidopsis thaliana) T-DNA knockout mutants of two CoA biosynthetic
      genes, HAL3A and HAL3B. The HAL3A gene encodes a 4'-phosphopantothenoyl-cysteine
      decarboxilase that generates 4'-phosphopantetheine. A second gene, HAL3B, whose
      gene product is 86% identical to that of HAL3A, is present in the Arabidopsis
      genome. HAL3A appears to have a predominant role over HAL3B according to their
      respective mRNA expression levels. The hal3a-1, hal3a-2, and hal3b mutants were
      viable and showed a similar growth rate as that in wild-type plants; in contrast,
      a hal3a-1 hal3b double mutant was embryo lethal. Unexpectedly, seedlings that
      were null for HAL3A and heterozygous for HAL3B (aaBb genotype) displayed a
      sucrose (Suc)-dependent phenotype for seedling establishment, which is in common
      with mutants defective in beta-oxidation. This phenotype was genetically
      complemented in aaBB siblings of the progeny and chemically complemented by
      pantethine. In contrast, seedling establishment of Aabb plants was not Suc
      dependent, proving a predominant role of HAL3A over HAL3B at this stage. Total
      fatty acid and acyl-CoA measurements of 5-d-old aaBb seedlings in medium lacking
      Suc revealed stalled storage lipid catabolism and impaired CoA biosynthesis; in
      particular, acetyl-CoA levels were reduced by approximately 80%. Taken together,
      these results provide in vivo evidence for the function of HAL3A and HAL3B, and
      they point out the critical role of CoA biosynthesis during early postgerminative
      growth.

PMID- 16415215
TI  - Poplar carbohydrate-active enzymes. Gene identification and expression analyses.
AB  - Over 1,600 genes encoding carbohydrate-active enzymes (CAZymes) in the Populus
      trichocarpa (Torr. & Gray) genome were identified based on sequence homology,
      annotated, and grouped into families of glycosyltransferases, glycoside
      hydrolases, carbohydrate esterases, polysaccharide lyases, and expansins. Poplar
      (Populus spp.) had approximately 1.6 times more CAZyme genes than Arabidopsis
      (Arabidopsis thaliana). Whereas most families were proportionally increased,
      xylan and pectin-related families were underrepresented and the GT1 family of
      secondary metabolite-glycosylating enzymes was overrepresented in poplar. CAZyme
      gene expression in poplar was analyzed using a collection of 100,000 expressed
      sequence tags from 17 different tissues and compared to microarray data for
      poplar and Arabidopsis. Expression of genes involved in pectin and hemicellulose
      metabolism was detected in all tissues, indicating a constant maintenance of
      transcripts encoding enzymes remodeling the cell wall matrix. The most abundant
      transcripts encoded sucrose synthases that were specifically expressed in wood
      forming tissues along with cellulose synthase and homologs of KORRIGAN and ELP1.
      Woody tissues were the richest source of various other CAZyme transcripts,
      demonstrating the importance of this group of enzymes for xylogenesis. In
      contrast, there was little expression of genes related to starch metabolism
      during wood formation, consistent with the preferential flux of carbon to cell
      wall biosynthesis. Seasonally dormant meristems of poplar showed a high
      prevalence of transcripts related to starch metabolism and surprisingly retained
      transcripts of some cell wall synthesis enzymes. The data showed profound changes
      in CAZyme transcriptomes in different poplar tissues and pointed to some key
      differences in CAZyme genes and their regulation between herbaceous and woody
      plants.

PMID- 16415217
TI  - Wound-induced terpene synthase gene expression in Sitka spruce that exhibit
      resistance or susceptibility to attack by the white pine weevil.
AB  - We analyzed the expression pattern of various terpene synthase (TPS) genes in
      response to a wounding injury applied to the apical leader of Sitka spruce (Picea
      sitchensis Bong. Carr.) genotypes known to be resistant (R) or susceptible (S) to
      white pine weevil (Pissodes strobi Peck.) attack. The purpose was to test if
      differences in constitutive or wound-induced TPS expression can be associated
      with established weevil resistance. All wounding treatments were conducted on 9
      year-old R and S trees growing under natural field conditions within the range of
      variation for weevil R and S genotypes. Representative cDNAs of the monoterpene
      synthase (mono-TPS), sesquiterpene synthase (sesqui-TPS), and diterpene synthase
      (di-TPS) classes were isolated from Sitka spruce to assess TPS transcript levels.
      Based on amino acid sequence similarity, the cDNAs resemble Norway spruce (Picea
      abies) (-)-linalool synthase (mono-TPS; PsTPS-Linl) and
      levopimaradiene/abietadiene synthase (di-TPS; PsTPS-LASl), and grand fir (Abies
      grandis) delta-selinene synthase (sesqui-TPS; PsTPS-Sell). One other mono-TPS was
      functionally identified as (-)-limonene synthase (PsTPS-Lim). No significant
      difference in constitutive expression levels for these TPSs was detected between
      R and S trees. However, over a postwounding period of 16 d, only R trees
      exhibited significant transcript accumulation for the mono- and sesqui-TPS
      tested. Both R and S trees exhibited a significant accumulation of PsTPS-LASl
      transcripts. An assessment of traumatic resin duct formation in wounded leaders
      showed that both R and S trees responded by forming traumatic resin ducts;
      however, the magnitude of this response was significantly greater in R trees.
      Collectively, our data imply that the induced resinosis response is an important
      aspect of defense in weevil R Sitka spruce trees growing under natural
      conditions.

PMID- 16415219
TI  - Breast implant advisory panel: more study on silicone leakage.

PMID- 16415218
TI  - G-protein-coupled receptor 1, G-protein Galpha-subunit 1, and prephenate
      dehydratase 1 are required for blue light-induced production of phenylalanine in
      etiolated Arabidopsis.
AB  - Different classes of plant hormones and different wavelengths of light act
      through specific signal transduction mechanisms to coordinate higher plant
      development. A specific prephenate dehydratase protein (PD1) was discovered to
      have a strong interaction with the sole canonical G-protein Galpha-subunit (GPA1)
      in Arabidopsis (Arabidopsis thaliana). PD1 is a protein located in the cytosol,
      present in etiolated seedlings, with a specific role in blue light-mediated
      synthesis of phenylpyruvate and subsequently of phenylalanine (Phe). Insertion
      mutagenesis confirms that GPA1 and the sole canonical G-protein-coupled receptor
      (GCR1) in Arabidopsis also have a role in this blue light-mediated event. In
      vitro analyses indicate that the increase in PD1 activity is the direct and
      specific consequence of its interaction with activated GPA1. Because of their
      shared role in the light-mediated synthesis of phenylpyruvate and Phe, because
      they are iteratively interactive, and because activated GPA1 is directly
      responsible for the activation of PD1; GCR1, GPA1, and PD1 form all of or part of
      a signal transduction mechanism responsible for the light-mediated synthesis of
      phenylpyruvate, Phe, and those metabolites that derive from that Phe. Data are
      also presented to confirm that abscisic acid can act through the same pathway. An
      additional outcome of the work is the confirmation that phenylpyruvate acts as
      the intermediate in the synthesis of Phe in etiolated plants, as it commonly does
      in bacteria and fungi.

PMID- 16415220
TI  - Call for ban on the non-therapeutic docking of dogs' tails.

PMID- 16415221
TI  - OIE expresses concern about avian influenza in Turkey.

PMID- 16415223
TI  - Animal Welfare Bill granted second reading.

PMID- 16415224
TI  - Internet consultation reveals EU citizens' interest in welfare.

PMID- 16415225
TI  - Increase in charges for CITES permits.

PMID- 16415227
TI  - Duty of care: new obligations, new challenges.

PMID- 16415231
TI  - Estimation of the relative risk of developing clinical scrapie: the role of prion
      protein (PrP) genotype and selection bias.
AB  - Prion protein (PrP) genotype data from statutory confirmed cases and from three
      non-case datasets have been used to calculate the odds ratio (or) for the
      development of clinical scrapie for an individual sheep of a given PrP genotype,
      compared with one possessing the "wild-type" ARQ/ARQ genotype. Logistic
      regression has been used to estimate the ors, and a multiple-test procedure has
      been used to evaluate the statistical significance of each comparison. The
      results are similar to those observed in other studies: the VRQ/VRQ genotype has
      or point estimates greater than 20; the ARQ/VRQ and ARH/VRQ genotypes have or
      point estimates between 5 and 20; AHQ/VRQ between 0.03 and 0.1; ARR/VRQ 0.4 and
      0.5; all the other PrP genotypes, excluding ARR/ARR, ARR/ARH and AHQ/ARH for
      which no clinical cases have been recorded have or point estimates of less than
      0.3. The estimates derived from each dataset are comparable, but not identical.
      This can be explained by plausible biases inherent in the sampling of the non
      case populations.

PMID- 16415232
TI  - Prevalence of thermophilic Campylobacter species in cats and dogs in two animal
      shelters in Ireland.
AB  - Rectal swabs or faecal samples for the isolation of Campylobacter species were
      taken from 120 dogs and cats in an animal shelter in which only one kitten showed
      signs of gastrointestinal disease, and rectal swabs were taken from 46 dogs, 22
      of which showed signs of gastrointestinal disease, in another shelter. At the
      first shelter, the swabs from 24 of 47 dogs (51.1 per cent) and 36 of 48 cats (75
      per cent) yielded a Campylobacter species. The rate of isolation was
      significantly higher from dogs and cats less than six months old, and
      significantly higher from cats than from dogs (P< or =0.05). At the second
      shelter Campylobacter species were isolated from 40 of 46 dogs (87 per cent), but
      there was no significant difference between the age groups. Campylobacter species
      were isolated from 19 (86.4 per cent) of the 22 dogs with signs of
      gastrointestinal disease and from 21 (87.5 per cent) of the 24 unaffected dogs.
      Several culture methods were applied to the samples collected from both shelters,
      and the combination significantly increased the recovery of Campylobacter
      species.

PMID- 16415233
TI  - Survey of parasite control on sheep farms in south-west England.

PMID- 16415234
TI  - Intracutaneous keratinising epithelioma in a mynah bird (Gracula religiosa).

PMID- 16415235
TI  - Notoedric mange caused by Notoedres cati in a pet African pygmy hedgehog
      (Atelerix albiventris).

PMID- 16415236
TI  - Balantidium, Cryptosporidium and Giardia species infections in indoor and outdoor
      pig production units in Croatia.

PMID- 16415237
TI  - Offering the best to patients: ethical issues associated with the provision of
      veterinary services.
AB  - Veterinary surgeons have long been perceived as animal advocates and yet their
      income is usually dependent on a third party: the owner. Given the ever
      increasing options now available to treat complex clinical conditions, it is
      important to consider which services should, rather than could, be offered to
      clients. Does the professional obligation to act as an animal advocate conflict
      or concord with the desire to operate a successful business? David Main discusses
      the ethical issues associated with the provision of professional services to
      clients and their animals.

PMID- 16415238
TI  - Quality of digital x-ray images.

PMID- 16415239
TI  - Bile fluke in otters and mink.

PMID- 16415242
TI  - Reporting zoonotic diseases.

PMID- 16415243
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16415244
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16415245
TI  - Footrot and interdigital dermatitis in sheep.

PMID- 16415246
TI  - Badger culling and bovine TB.

PMID- 16415251
TI  - Endogenous S-nitrosoglutathione modifies 5-lipoxygenase expression in airway
      epithelial cells.
AB  - S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several
      beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and
      GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is
      the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes
      (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we
      have studied the effect of GSNO on the expression of 5-LO in human airway A549
      cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells
      in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase
      in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO
      expression and LT production. We also found that airway epithelial cells had
      gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on
      5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a
      convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma.
      Our data demonstrate that GSNO levels<or=1 microM, likely recapitulating those in
      the asthmatic airway, increase 5-LO expression, an effect that may increase
      inflammation and bronchoconstriction. However, GSNO at concentrations>5microM
      suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO
      expression in the clinical setting.

PMID- 16415250
TI  - Expression of the reverse tetracycline-transactivator gene causes emphysema-like
      changes in mice.
AB  - The doxycycline-inducible, gene regulatory system allows tight control of
      transgene expression for the study of organ development and disease pathogenesis.
      Multiple recent reports have employed this model to investigate various lung
      diseases including emphysema. For our study, we used this transgenic system to
      test whether prolonged, lung-specific, overexpression of the serine protease
      urokinase plasminogen activator (uPA) would result in alveolar wall destruction.
      Double transgenic mice were generated that possessed: (1) the rat Clara cell
      secretory protein promoter controlling the reverse tetracycline transactivator
      gene (CCSP:rtTA) and (2) the tetracycline operator controlling the murine uPA
      cDNA (tet[O]:muPA). Mice were treated with doxycycline beginning at age 6 wk to
      initiate uPA overexpression. Single transgenic and wild-type animals served as
      controls. A second group of double transgenic and control animals were maintained
      off of doxycycline. At ages 10, 18, and 30 wk, the mice underwent measurements of
      alveolar size, lung compliance, and total lung capacity. We found that, although
      the uPA overexpressing mice demonstrated an emphysema phenotype, similar
      abnormalities occurred in the CCSP-rtTA control animals. These CCSP-rtTA-related
      alterations occurred even without doxycycline exposure. Evaluation of a second
      transgenic line possessing the human surfactant protein C promoter controlling
      rtTA expression also exhibited lung abnormalities consistent with emphysema.
      These findings indicate that pulmonary epithelial expression of rtTA alone causes
      an emphysema phenotype in mice. Therefore, when using this system to study
      emphysema pathogenesis, the inclusion of proper controls is essential for
      accurate data interpretation.

PMID- 16415252
TI  - Surfactant as an airway smooth muscle relaxant.
AB  - A variety of clinical and experimental evidence indicates that surfactant may be
      important in the pathogenesis and treatment of asthma. The purpose of this study
      was to determine the pharmacologic effect of pulmonary surfactant and its major
      lipid and protein constituents on bronchial smooth muscle. First-generation
      bronchi from male Sprague-Dawley rats were contracted with methacholine and
      exposed to two kinds of surfactant: whole rat surfactant and two bovine
      surfactant extracts in clinical use. The latter lack the hydrophilic surfactant
      associated proteins (SP)-A and SP-D. All the surfactants relaxed the rat bronchi
      in a concentration-dependent manner; however, whole rat surfactant was more
      potent than the bovine extracts. Both surfactant lipids and SP-A contributed to
      the bronchial relaxation. The relaxation response produced by the highest
      concentration (0.5 mg/ml) of whole rat surfactant was equivalent to that caused
      by substance P (5 microM) and approximately half of that caused by 1 microM
      isoproterenol. The relaxation response was epithelium-dependent and blocked by
      indomethacin but not by N-omega-nitro-L-arginine methyl ester. We conclude that
      surfactant can relax airway smooth muscle directly via a prostanoid-mediated,
      epithelium-dependent process that does not involve nitric oxide synthase.

PMID- 16415253
TI  - Systematic reviews of meta-analyses: applications and limitations.

PMID- 16415254
TI  - Where now for pharmacist led medication review?

PMID- 16415249
TI  - Airway mucus: From production to secretion.
AB  - Mucus hypersecretion is a phenotype associated with multiple obstructive lung
      diseases. However, in spite of its nefarious reputation under pathologic
      conditions, there are significant benefits to having low levels of mucus present
      in the airways at baseline, such as the ability to trap and eliminate inhaled
      particles and to prevent desiccation of airway surfaces. Mucins are high
      molecular-weight glycoproteins that are the chief components that render
      viscoelastic and gel-forming properties to mucus. Recent advances in animal
      models and in vitro systems have provided a wealth of information regarding the
      identification of the mucin genes that are expressed in the lungs, the signal
      transduction pathways that regulate the expression of these mucins, and the
      secretory pathways that mediate their release into the airways. In addition, the
      clinical and pathologic literature has corroborated many of the basic laboratory
      findings. As a result, mucin overproduction and hypersecretion are moving away
      from being markers of disease and toward being testable as functional components
      of lung disease processes.

PMID- 16415255
TI  - Licensing Britain's alcohol epidemic.

PMID- 16415257
TI  - Paths to and from poverty in late 19th century novels.
AB  - Late 19th century novels provide graphic descriptions of working and living
      conditions and their impact on population health, in particular the detrimental
      effects of hunger, poor housing, environmental conditions, hazardous work and
      poor pay, smoking and alcohol and crime, but also the transformative
      possibilities of social and political action. The popularity of these novels
      helped raise the collective conscience of citizens and illuminated the direction
      for 20th century welfare reforms. Yet many of these problems remain and the
      pathways to and from poverty are still recognisable today. Although novels are
      now less central in conveying social information, re-reading these novels enables
      us to understand how social and economic circumstances were understood at the
      time and what led to social and political change.

PMID- 16415256
TI  - Indicators of socioeconomic position (part 2).
AB  - This is the second part of a glossary on indicators of socioeconomic position
      used in health research (the first part was published in the January issue of the
      journal).

PMID- 16415258
TI  - Do urban regeneration programmes improve public health and reduce health
      inequalities? A synthesis of the evidence from UK policy and practice (1980
      2004).
AB  - OBJECTIVES: To synthesise data on the impact on health and key socioeconomic
      determinants of health and health inequalities reported in evaluations of
      national UK regeneration programmes. DATA SOURCES: Eight electronic databases
      were searched from 1980 to 2004 (IBSS, COPAC, HMIC, IDOX, INSIDE, Medline,
      Urbadisc/Accompline, Web of Knowledge). Bibliographies of located documents and
      relevant web sites were searched. Experts and government departmental libraries
      were also contacted. REVIEW METHODS: Evaluations that reported achievements
      drawing on data from at least two target areas of a national urban regeneration
      programme in the UK were included. Process evaluations and evaluations reporting
      only business outcomes were excluded. All methods of evaluation were included.
      Impact data on direct health outcomes and direct measures of socioeconomic
      determinants of health were narratively synthesised. RESULTS: 19 evaluations
      reported impacts on health or socioeconomic determinants of health; data from 10
      evaluations were synthesised. Three evaluations reported health impacts; in one
      evaluation three of four measures of self reported health deteriorated, typically
      by around 4%. Two other evaluations reported overall reductions in mortality
      rates. Most socioeconomic outcomes assessed showed an overall improvement after
      regeneration investment; however, the effect size was often similar to national
      trends. In addition, some evaluations reported adverse impacts. CONCLUSION: There
      is little evidence of the impact of national urban regeneration investment on
      socioeconomic or health outcomes. Where impacts have been assessed, these are
      often small and positive but adverse impacts have also occurred. Impact data from
      future evaluations are required to inform healthy public policy; in the meantime
      work to exploit and synthesise "best available" data is required.

PMID- 16415259
TI  - Bonding versus bridging social capital and their associations with self rated
      health: a multilevel analysis of 40 US communities.
AB  - STUDY OBJECTIVE: Few studies have distinguished between the effects of different
      forms of social capital on health. This study distinguished between the health
      effects of summary measures tapping into the constructs of community bonding and
      community bridging social capital. DESIGN: A multilevel logistic regression
      analysis of community bonding and community bridging social capital in relation
      to individual self rated fair/poor health. SETTING: 40 US communities.
      PARTICIPANTS: Within community samples of adults (n = 24 835), surveyed by
      telephone in 2000-2001. MAIN RESULTS: Adjusting for community sociodemographic
      and socioeconomic composition and community level income and age, the odds ratio
      of reporting fair or poor health was lower for each 1-standard deviation (SD)
      higher community bonding social capital (OR = 0.86; 95% = 0.80 to 0.92) and each
      1-SD higher community bridging social capital (OR = 0.95; 95% CI = 0.88 to 1.02).
      The addition of indicators for individual level bonding and bridging social
      capital and social trust slightly attenuated the associations for community
      bonding social capital (OR = 0.90, 95% CI = 0.84 to 0.97) and community bridging
      social capital (OR = 0.96, 95% CI = 0.89 to 1.03). Individual level high formal
      bonding social capital, trust in members of one's race/ethnicity, and generalised
      social trust were each significantly and inversely related to fair/poor health.
      Furthermore, significant cross level interactions of community social capital
      with individual race/ethnicity were seen, including weaker inverse associations
      between community bonding social capital and fair/poor health among black persons
      compared with white persons. CONCLUSIONS: These results suggest modest protective
      effects of community bonding and community bridging social capital on health.
      Interventions and policies that leverage community bonding and bridging social
      capital might serve as means of population health improvement.

PMID- 16415260
TI  - Acceptability of domestic violence against women in the European Union: a
      multilevel analysis.
AB  - STUDY OBJECTIVE: The acceptability of domestic violence against women (DVAW)
      plays an important part in shaping the social environment in which the victims
      are embedded, which in turn may contribute either to perpetuate or to reduce the
      levels of DVAW in our societies. This study analyses correlates of the
      acceptability of DVAW in the European Union (EU). DESIGN: Three level ordinal
      logistic regression of 13 457 people nested within 212 localities (cities),
      nested within 15 countries of the EU. Sampling is multistage with random
      probability. All interviews were face to face in people's homes. The outcome
      variable was acceptability of DVAW. Multiple correlates at the individual,
      locality, and country level were analysed. SETTING: European Union, 1999.
      PARTICIPANTS: National data were used of residents 15 years old and above of all
      member states in 1999 (n = 13 457). Average response rate was 47%, although it
      varied across countries (23%-73%). MAIN RESULTS: Higher levels of acceptability
      were reported by those who perceived DVAW as less severe and less frequent.
      Acceptability is higher among men who know a perpetrator and lower among men who
      know a victim. Victim blaming attitude is associated with higher levels of
      acceptability. In countries with higher gender empowerment measure the difference
      in acceptability among those who blame and those who do not blame the victim is
      greater. CONCLUSIONS: There are still widespread attitudes in the EU such as
      victim blaming that condone DVAW, contributing to a climate of social
      acceptability of DVAW. Further efforts to reduce the acceptability of DVAW are
      still needed.

PMID- 16415261
TI  - Socioeconomic determinants of health related quality of life in childhood and
      adolescence: results from a European study.
AB  - STUDY OBJECTIVE: The objective of this study was to investigate the impact of two
      different socioeconomic status (SES) measures on child and adolescent self
      reported health related quality of life (HRQoL). The European KIDSCREEN project
      aims at simultaneous developing, testing, and implementing a generic HRQoL
      instrument. DESIGN AND SETTING: The pilot version of the questionnaire was
      applied in school surveys to students from 8 to 18 years of age, as well as to
      their parents, together with such determinants of health status as two SES
      indicators, the parental educational status and the number of material goods in
      the family (FAS, family affluence scale). PARTICIPANTS: Students from seven
      European countries: 754 children (39.8%; mean: 9.8 years), and 1142 adolescents
      (60.2 %; mean: 14.1 years), as well as their respective parents. MAIN RESULTS: In
      children, a higher parental educational status was found to have a significant
      positive impact on the KIDSCREEN dimensions: physical wellbeing, psychological
      wellbeing, moods and emotions, bullying and perceived financial resources.
      Increased risk of low HRQoL was detected for adolescents in connection with their
      physical wellbeing. Family wealth plays a part for children's physical wellbeing,
      parent relations and home life, and perceived financial resources. For
      adolescents, family wealth furthermore predicts HRQoL on all KIDSCREEN
      dimensions. CONCLUSIONS: There is evidence to suggest that exposure to low
      parental educational status may result in a decreased HRQoL in childhood, whereas
      reduced access to material (and thereby social) resources may lead to a lower
      HRQoL especially in adolescence.

PMID- 16415263
TI  - Could dehydration in infancy lead to high blood pressure?

PMID- 16415262
TI  - Roads, railways, and childhood cancers.
AB  - STUDY OBJECTIVES: To locate geographical sources of engine exhaust emissions in
      Great Britain and to link them with the birth addresses of children dying from
      cancer. To estimate the cancer initiating roles of nearby roads and railways and
      to measure effective ranges. DESIGN: Birth and death addresses of all children
      born between 1955 and 1980 in Great Britain, and dying from leukaemia or other
      cancer during those years, were linked to locations of railway stations, bus
      stations, ferry terminals, railways, roads, canals, and rivers. Nearest distances
      to births and deaths were measured, and migration data relating to children who
      had moved house were analysed. Excesses of close to hazard birth addresses,
      compared with close to hazard death addresses, indicate a high prenatal or early
      postnatal risk of cancer initiation. SETTING AND SUBJECTS: Child cancer birth and
      death addresses and their map references were extracted from an earlier inquiry.
      Map references of putative hazards were downloaded from the Ordnance Survey
      national digital map of Great Britain. These data are recorded to a precision of
      one metre and have ground accuracies around 20 metres. MAIN RESULTS: Significant
      birth excesses were found within short distances of bus stations, railway
      stations, ferries, railways, and A,B class roads, with a relative risk of 2.1
      within 100 m, tapering to neutral after 3.0 km. About 24% of child cancers were
      attributable to these joint birth proximities. Roads exerted the major effect.
      CONCLUSIONS: Child cancer initiations are strongly determined by prenatal or
      early postnatal exposures to engine exhaust gases, probably through maternal
      inhalation and accumulation of carcinogens over many months. The main active
      substance is probably 1,3-butadiene.

PMID- 16415264
TI  - Birth weight, adult blood pressure, and blood pressure reactions to acute
      psychological stress.

PMID- 16415265
TI  - Breast feeding is related to C reactive protein concentration in adult women.
AB  - OBJECTIVE: To assess the influence of infant breast feeding on C reactive protein
      (CRP), a marker of low grade inflammation associated with cardiovascular
      mortality independent of serum cholesterol concentrations. DESIGN: Serum CRP,
      total cholesterol, anthropometric, and blood pressure measurements were performed
      along with assessment of infant breast feeding duration, birth weight, smoking
      status, adult socioeconomic status, number of health problems, and hormonal
      contraceptive use. SETTING: A New Zealand predominantly European descent
      community birth cohort. PARTICIPANTS: 822 men and women aged 26 years. MAIN
      RESULTS: There was a significant linear relation (p<0.001) between duration of
      breast feeding and adult CRP level in women. The geometric means (IQR) for CRP
      were 2.22 (1, 4) mg/l for women breast fed for six months or more and 3.95 (2, 8)
      mg/l for women not breast fed (ratio, 95% confidence interval (CI): 0.69 (0.55 to
      0.87). The linear association between cholesterol and breast feeding was also
      significant (p = 0.01), the geometric mean (IQR) total cholesterol levels being
      4.62 (4.10, 5.10) for those breast fed for six months or more and 5.04 (4.5,
      5.80) for those not breast fed (ratio, 95% CI: 0.92 (0.87, 0.98). There was no
      relation between CRP or total cholesterol and duration of breast feeding in men.
      CONCLUSIONS: The findings of lower CRP with an increased duration of breast
      feeding in women suggest early postnatal nutrition may influence long term
      cardiovascular risk.

PMID- 16415266
TI  - Is there a "school effect" on pupil outcomes? A review of multilevel studies.
AB  - STUDY OBJECTIVE: The school environment is of importance for child outcomes.
      Multilevel analyses can separate determinants operating at an individual level
      from those operating at a contextual level. This paper aims to systematically
      review multilevel studies of school contextual effects on pupil outcomes. DESIGN:
      Key word searching of five databases yielded 17 cross sectional or longitudinal
      studies meeting the inclusion criteria. Results are summarised with reference to
      type of school contextual determinant. MAIN RESULTS: Four main school effects on
      pupil outcomes were identified. Having a health policy or antismoking policy, a
      good school climate, high average socioeconomic status, and urban location had a
      positive effect on pupil outcomes. Outcomes under study were smoking habits,
      wellbeing, problem behaviour, and school achievement. CONCLUSIONS: Despite the
      different pupil outcomes and the variety of determinants used in the included
      papers, a school effect was evident. However, to improve our understanding of
      school effects, presentations of results from multilevel studies need to be
      standardised. Intraclass correlation and explained between school variance give
      relevant information on factors in the school environment influencing pupil
      outcomes, and should be included in all multilevel studies. Inclusion of pupil
      level predictors in the multilevel models should be based on theoretical
      considerations of how schools and communities are interconnected and how pupils
      and their families are influenced by school contextual factors.

PMID- 16415267
TI  - Country material distribution and adolescents' perceived health: multilevel study
      of adolescents in 27 countries.
AB  - OBJECTIVE: To assess the impact of country material distribution on adolescents'
      perceptions of health. DESIGN: Cross sectional multilevel study. SETTING: Data
      were collected from the school based health behaviour in school aged children:
      WHO cross national study 1997/98, which includes students from 27 European and
      North American countries. PARTICIPANTS: 12 0381 students in year 6, 8, and 10 who
      were attending school classes on the day of data collection. MAIN RESULT:
      Adolescents in countries with a high dispersion of family affluence were more
      likely to have self rated poor health even after controlling for individual
      family level of affluence and family social resources. CONCLUSION: There are
      substantial inequalities in subjective health across European and North American
      countries related to the distribution of family material resources in these
      countries.

PMID- 16415268
TI  - Children's use of general practitioner services in the five Nordic countries.
AB  - OBJECTIVE: To compare socioeconomic, sociodemographic, and living area
      differences in children's use of GP services in five Nordic countries from the
      1980s to the 1990s and to analyse trends during the period. DESIGN: Cross
      sectional population surveys using random samples comprising 3000 children aged 2
      17 years were conducted in 1984 and 1996 in five Nordic countries. Time trends in
      use of GP services were studied in each country by age, sex, parents' highest
      level of education, and living area. SETTING: Five Nordic countries, Denmark,
      Finland, Iceland, Norway, and Sweden in 1984 and 1996. PARTICIPANTS: A total
      sample of 15 000 children aged 2-17 years. Altogether 3000 children were selected
      at random from the national population registers of the national bureaus of
      statistics in each country. MAIN OUTCOME: Health services utilisation on the
      basis of responses to a questionnaire item asking whether the parents had
      consulted a GP with regard to their children's health during the previous three
      months. MAIN RESULTS: The prevalence of children's utilisation of GP services
      varied from 14% in 1984 in Sweden to 28% in 1996 in Iceland. A clear time trend
      towards increasing utilisation of GP services (p<0.05) was found in all countries
      except in Denmark. Odds ratios for time trends (1984 = 1.00) varied from 1.22
      (1.02 to 1.46) in Sweden to 1.92 (1.62 to 2.30) in Norway. After adjusting for
      independent variables, a statistically borderline significant declining
      utilisation trend (OR = 0.85 (0.70 to 1.03)) was found for Denmark. CONCLUSION:
      Children's use of GP services has increased significantly in four of the five
      Nordic countries.

PMID- 16415270
TI  - Associations between exposure to ambient photochemical oxidants and the vitality
      or mental health domain of the health related quality of life.
AB  - BACKGROUND: Ambient air pollution may affect the health related quality of life
      (HRQOL) of people, as assessed by the vitality (VT) and mental health (MH)
      domains of the SF-36 health survey (SF-36). METHODS: In a nationwide survey, 4500
      people aged 20 years and older were selected from the entire population of Japan
      by stratified random sampling in October 2002. A total of 2896 subjects filled
      out the self administered questionnaire that included the SF-36 and demographic
      characteristics. Data were linked from the questionnaires with the data on air
      pollutants in the cities where the subjects resided. The paper examined the
      relations between the mean concentration of each air pollutant and the VT or MH
      score on the SF-36 using analysis of covariance. RESULTS: On crude analysis, the
      respondents who were exposed to a higher mean two month concentration of
      photochemical oxidants (Ox) showed a significant linear trend toward lower VT
      score (p = 0.028). This association remained even after adjustment for subjective
      demographic characteristics and meteorological variables (p = 0.033). There was a
      common tendency that subjects who were exposed to higher concentrations of Ox had
      a lower mean VT or MH score; however, there was a significant association only
      between Ox concentration and VT score. CONCLUSION: The score on the VT domain of
      the SF-36 was associated with the mean concentration of Ox during the previous
      two month period. Assessing the health effects of air pollution by measuring the
      HRQOL, such as by using the SF-36, may provide a new method of formulating air
      pollution policies.

PMID- 16415269
TI  - Bladder cancer mortality and private well use in New England: an ecological
      study.
AB  - STUDY OBJECTIVE: To investigate the possible relation between bladder cancer
      mortality among white men and women and private water use in New England, USA,
      where rates have been persistently raised and use of private water supplies
      (wells) common. DESIGN: Ecological study relating age adjusted cancer mortality
      rates for white men and women during 1985-1999 and proportion of persons using
      private water supplies in 1970. After regressing mortality rates on population
      density, Pearson correlation coefficients were computed between residual rates
      and the proportion of the population using private water supplies, using the
      state economic area as the unit of calculation. Calculations were conducted
      within each of 10 US regions. SETTING: The 504 state economic areas of the
      contiguous United States. PARTICIPANTS: Mortality analysis of 11 cancer sites,
      with the focus on bladder cancer. MAIN RESULTS: After adjusting for the effect of
      population density, there was a statistically significant positive correlation
      between residual bladder cancer mortality rates and private water supply use
      among both men and women in New England (men, r = 0.42; women, r = 0.48) and New
      York/New Jersey (men, r = 0.49; women, r = 0.62). CONCLUSIONS: Use of well water
      from private sources, or a close correlate, may be an explanatory variable for
      the excess bladder cancer mortality in New England. Analytical studies are
      underway to clarify the relation between suspected water contaminants,
      particularly arsenic, and raised bladder cancer rates in northern New England.

PMID- 16415271
TI  - Investigating the relation between placement of Quit antismoking advertisements
      and number of telephone calls to Quitline: a semiparametric modelling approach.
AB  - STUDY OBJECTIVES: Quitline-an antismoking advertising and a telephone helpline
      service-is an effective public health intervention strategy for tobacco control.
      The objective of this short report is to model the relation between placement of
      antismoking advertisements and calls to Quitline on a given day. METHODS/DESIGN:
      Data on daily Quitline antismoking advertisements, television target audience
      rating points (TARPS), and calls to Quitline Victoria were studied for the period
      1 August 2000 and 31 July 2001. The outcome-calls to Quitline-is a count and thus
      assumed to follow a Poisson distribution. Generalised partial linear models were
      used to model the logarithm of mean daily calls as a non-parametric function of
      time and a linear parametric function of the day of week, number of
      advertisements, and TARPS. MAIN RESULTS: Peak calls to Quitline Victoria occurred
      during Monday to Wednesday with around three times as many calls compared with
      Sunday. Both placement of Quitline advertisements (p<0.001) and an increase in
      TARPS (p<0.001) on a given day significantly increased the number of calls made
      to Quitline Victoria. The model adequately captured fluctuations in call volume
      and diagnostics showed no model inadequacy. CONCLUSIONS: In this short report the
      emphasis is on modelling the parametric components-day of week, placement of
      advertisements, and TARPS on call volume. The dynamics of the underlying time
      trend in call volume is captured in a non-parametric component. Future analysis
      of hourly data would provide additional information to assess different media
      buying strategies that might increase call volume.

PMID- 16415272
TI  - Change in sex ratio at birth in Sardasht (north west of Iran) after chemical
      bombardment.

PMID- 16415273
TI  - Brain natriuretic peptide is a prognostic parameter in chronic lung disease.
AB  - RATIONALE: The detection of pulmonary hypertension in patients with chronic lung
      disease has prognostic implications. The brain natriuretic peptide (BNP) has been
      suggested as a noninvasive marker for the presence and severity of pulmonary
      hypertension. OBJECTIVES: We evaluated circulating BNP levels as a parameter for
      the presence and severity of pulmonary hypertension in patients with chronic lung
      disease. METHODS: BNP levels were measured in 176 consecutive patients with
      various pulmonary diseases. Right heart catheterization, lung functional testing,
      and a 6-min walk test were performed. The mean follow-up time was nearly 1 yr.
      MEASUREMENTS AND MAIN RESULTS: Significant pulmonary hypertension (mean pulmonary
      artery pressure > 35 mm Hg) was diagnosed in more than one-fourth of patients and
      led to decreased exercise tolerance and life expectancy. Elevated BNP
      concentrations identified significant pulmonary hypertension with a sensitivity
      of 0.85 and specificity of 0.88 and predicted mortality. Moreover, BNP served as
      a risk factor of death independent of lung functional impairment or hypoxemia in
      uni- and multivariate analysis. CONCLUSION: We suggest BNP as a prognostic marker
      and as screening parameter for significant pulmonary hypertension in chronic lung
      disease.

PMID- 16415274
TI  - A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary
      fibrosis via CCL18.
AB  - RATIONALE: Recently, models of macrophage activation have been revised.
      Macrophages stimulated with Th2 cytokines have been classified as alternatively
      activated. OBJECTIVES: This article examines the expression and regulation of CC
      chemokine ligand 18 (CCL18), a marker of alternative activation, by human
      alveolar macrophages (AMs). METHODS: AM were obtained from bronchoalveolar lavage
      (BAL) fluid of patients with idiopathic pulmonary fibrosis, sarcoidosis, or
      hypersensitivity pneumonitis (n = 69) and healthy volunteers (n = 22). Expression
      of CCL18 was determined by quantitative reverse transcriptase-polymerase chain
      reaction, in situ hybridization, flow cytometry, and immunohistochemistry,
      respectively. MEASUREMENTS AND MAIN RESULTS: Spontaneous CCL18 production by BAL
      derived cells was markedly increased in patients with pulmonary fibrosis and
      correlated negatively with pulmonary function test parameters. CCL18 gene
      expression and protein production were up-regulated in normal AMs after Th2
      cytokine stimulation and/or coculture with human lung fibroblasts. Native
      collagen significantly up-regulated CCL18 expression in normal AMs activated with
      Th2 cytokines via a mechanism mediated by beta2-integrin/ scavenger receptor(s).
      Culture supernatants of AMs from patients with idiopathic pulmonary fibrosis
      increased collagen production by normal lung fibroblasts partly mediated via
      CCL18. CONCLUSIONS: Our findings suggest that AMs from patients with pulmonary
      fibrosis disclose a phenotype of alternative activation and might be a part of a
      positive feedback loop with lung fibroblasts perpetuating fibrotic processes.

PMID- 16415275
TI  - Alteration of fibroblast architecture and loss of Basal lamina apertures in human
      emphysematous lung.
AB  - RATIONALE: In normal human lung, single alveolar fibroblasts link capillary
      endothelium to type 2 pneumocytes through apertures in the endothelial and
      epithelial basal laminae. These fibroblasts are hypothesized to play a role in
      cellular communication between the endothelium and epithelium and are positioned
      to provide leukocytes a surface on which they may migrate through the
      interstitium. OBJECTIVES: To determine whether fibroblasts link the endothelium
      to the epithelium in emphysematous lung and to compare basal lamina aperture
      frequency with previously published results. METHODS: We performed transmission
      electron microscopy serial section three-dimensional reconstructions of
      emphysematous regions of human alveolar wall and a quantitative analysis of basal
      lamina apertures beneath 403 type 2 pneumocytes. MEASUREMENTS AND MAIN RESULTS:
      Our three-dimensional reconstruction demonstrated that the fibroblasts subtending
      type 2 pneumocytes in emphysematous lung no longer link these epithelial cells to
      the capillary endothelium through basal lamina apertures. Basal lamina apertures
      may be absent below some type 2 pneumocytes. Our morphometric analysis showed
      that their frequency and area beneath type 2 pneumocytes is significantly reduced
      in emphysematous regions when compared with nonemphysematous regions of matched
      control lung. CONCLUSIONS: We conclude that the endothelial/fibroblast/epithelial
      linkage is disrupted in emphysematous human lungs and postulate this disruption
      may disturb leukocyte migration and account for their accumulation in the
      alveolar interstitium of emphysematous lung tissue.

PMID- 16415276
TI  - Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin
      model.
AB  - RATIONALE: The model most often used to study the pathogenesis of pulmonary
      fibroses is the bleomycin (BLM)-induced lung fibrosis model. Several treatments
      have been efficacious in this model, but not in the clinic. OBJECTIVES: To
      describe the time course of inflammation and fibrosis in the BLM model and to
      study the effect of timing of antiinflammatory and antifibrotic treatments on
      efficacy. METHODS AND MEASUREMENTS: Rats were given single intratracheal
      injections of BLM on Day 0. At specified time points, 10 rats were killed and
      their lungs studied for proinflammatory cytokines and for profibrotic growth
      factor mRNA. After a single intratracheal injection of BLM on Day 0, rats were
      treated from Day 1 or 10 daily with oral prednisolone (10 mg/kg) or oral imatinib
      mesylate (50 mg/kg) for 21 d. RESULTS: After BLM administration, the expression
      of inflammatory cytokines was elevated and returned to background levels at later
      time points. Profibrotic gene expression peaked between Days 9 and 14 and
      remained elevated till the end of the experiment, suggesting a "switch" between
      inflammation and fibrosis in this interval. Antiinflammatory treatment (oral
      prednisolone) was beneficial when commenced at Day 1, but had no effect if
      administered from Day 10 onward. However, imatinib mesylate was effective
      independently of the dosing regime. CONCLUSIONS: The response of the BLM model to
      antifibrotic or antiinflammatory interventions is critically dependent on timing
      after the initial injury.

PMID- 16415277
TI  - Power spectral analysis of heart rate variability in patients with Charcot's
      neuroarthropathy.
AB  - Charcot's or neuropathic osteoarthropathy is one of the most debilitating
      orthopedic sequelae of diabetes mellitus. Distinguishing Charcot's
      neuroarthropathy from clinically similar conditions may be challenging. The
      neurovascular theory postulates that Charcot's neuroarthropathy may be secondary
      to sympathetic denervation of the lower-extremity vasculature. A convenient
      method for assessing autonomic neuropathy in patients with Charcot's
      neuroarthropathy is needed. Short-term power spectral analysis (PSA) of heart
      rate variability (HRV), a noninvasive and quantitative method for assessing
      autonomic neuropathy, may be advantageous compared with the traditionally used
      Ewing's cardiovascular reflex tests. However, there are limitations to the
      clinical use of PSA of HRV because of poor standardization. We standardized PSA
      of HRV and assessed autonomic neuropathy in 17 people with acute Charcot's
      neuroarthropathy using PSA of HRV versus Ewing's tests. More patients with
      Charcot's neuroarthropathy were diagnosed as having autonomic neuropathy with PSA
      of HRV than with Ewing's tests (94% versus 82%); however, no significant
      difference between the two methods was found. The results of this study suggest
      that PSA of HRV requires minimal patient collaboration and time expenditure
      compared with Ewing's tests and may be useful in detecting autonomic neuropathy
      in patients with Charcot's neuroarthropathy.

PMID- 16415278
TI  - Casting methods and plantar pressure: effects of custom-made foot orthoses on
      dynamic plantar pressure distribution.
AB  - Foot orthoses are widely used to treat various foot problems. A literature search
      revealed no publications on differences in plantar pressure distribution
      resulting from casting methods for foot orthoses. Four casting methods were used
      for construction of orthoses. Two foam box techniques were used: accommodative
      full weightbearing method (A) and functional semiweightbearing method (B). Also,
      two suspension plaster casting techniques were used: accommodative casting (C)
      and functional subtalar joint neutral position (Root) method (D). Their effects
      on contact area, plantar pressure, and walking convenience were evaluated. All
      orthoses increased the total contact area (mean, 17.4%) compared with shoes
      without orthoses. Differences in contact areas between orthoses for total plantar
      surface were statistically significant. Peak pressures for the total plantar
      surface were lower with orthoses than without orthoses (mean, 22.8%). Among
      orthoses, only the difference between orthoses A and B was statistically
      significant. Differences between orthoses for the forefoot were small and not
      statistically significant. The gait lines of the shoe without an insole and of
      the accommodative orthoses are more medially located than those of functional
      orthoses. Walking convenience in the shoe was better rated than that with
      orthoses. There were no differences in perception of walking convenience between
      orthoses A, B, and C. Orthosis D had the lowest convenience rating. The four
      casting methods resulted in differences between orthoses with respect to contact
      areas and walking convenience but only slight differences in peak pressures.

PMID- 16415279
TI  - Endoscopic decompression of intermetatarsal nerve entrapment: a retrospective
      study.
AB  - Sixty-nine patients who had 96 interspaces decompressed were retrospectively
      reviewed to assess the efficacy of the endoscopic decompression of the
      intermetatarsal nerve procedure. Cases were evaluated between October 1, 1993,
      and December 31, 1999. Of the 69 patients, 14 were men and 55 were women, and
      their average age was 50.6 years. Of the 96 interspaces released, 39 were second
      interspaces and 57 were third interspaces. Nine interspaces were lost to follow
      up. There were 75 interspaces with excellent or good results (86%) and 12 with
      poor results (14%). Of the interspaces with poor results, five required further
      surgery. Those five interspaces, in five patients, were treated with traditional
      neurectomy. The other patients, accounting for seven interspaces, who classified
      their result as poor declined any further surgery. Evaluation of these cases was
      by means of medical chart review only, where the patient's success or failure was
      based on the patient's subjective assessment. None of the patients who underwent
      decompression developed a true amputation neuroma.

PMID- 16415280
TI  - Clinical and experimental models of the midtarsal joint: proposed terms of
      reference and associated terminology.
AB  - Recent debate and literature have provided impetus to the growing body of thought
      that we should not model the midtarsal joint as having two simultaneous axes of
      rotation but as having a single instantaneous axis of rotation. Building on this
      concept, we present new reference terminology and propose that descriptions of
      midtarsal joint kinetics and kinematics relate to moments and motion in the
      cardinal body planes as defined by the x-, y-, and z-axes of the local reference
      system of the calcaneus. This replaces the existing terminology that describes
      the oblique and longitudinal axes for the midtarsal joint. The purpose of the new
      terms of reference and terminology is to aid in the communication of ideas and
      concepts regarding the biomechanics of the midtarsal joint among clinicians and
      between researchers and clinicians. It will also allow integration of the
      midtarsal joint into the emerging biomechanical model of the lower limb, promote
      consistency in discussions of the joint, and ease understanding of the
      interrelationships between the kinetics and the kinematics of the articulations
      in the foot and lower limb and their relationship to pathology and clinical
      practice.

PMID- 16415281
TI  - Effect of foot posture and inverted foot orthoses on hallux dorsiflexion.
AB  - A pronated foot posture is considered to be a factor in limitation of
      dorsiflexion at the first metatarsophalangeal joint during weightbearing.
      Customized foot orthoses are widely used to increase dorsiflexion at the first
      metatarsophalangeal joint in people with pronated feet. However, the effect of
      foot posture and customized foot orthoses on maximum first metatarsophalangeal
      joint dorsiflexion has not been widely investigated. This study sought to
      determine 1) the relationship between foot posture and static maximum first
      metatarsophalangeal joint dorsiflexion and 2) the effect of customized foot
      orthoses on static maximum first metatarsophalangeal joint dorsiflexion in people
      with pronated feet. Foot posture was assessed using the Foot Posture Index.
      Static maximum first metatarsophalangeal joint dorsiflexion of the right foot was
      determined using a goniometer while participants stood relaxed with and without
      Blake-style inverted (30 degrees) foot orthoses positioned under their feet.
      There was a significant negative correlation between Foot Posture Index and
      static maximum first metatarsophalangeal joint dorsiflexion (r = -0.587).
      Inverted (30 degrees) foot orthoses increased the magnitude of static maximum
      first metatarsophalangeal joint dorsiflexion from 83.4 degrees to 85.3 degrees in
      participants with an excessively pronated foot posture. However, this difference
      was not statistically significant. People with pronated feet are more likely to
      exhibit limitation of dorsiflexion at the first metatarsophalangeal joint during
      gait, and inverted foot orthoses are unlikely to be effective in increasing
      dorsiflexion at the first metatarsophalangeal joint in these people.

PMID- 16415282
TI  - Evaluating costs for onychomycosis treatments: a practitioner's perspective.
AB  - Onychomycosis is a common problem. The desired outcome of treatment for patients
      and clinicians is complete cure (negative culture and negative potassium
      hydroxide examination results plus a completely normal nail). This cost analysis
      sought to determine the cost-effectiveness of treatments for onychomycosis using
      complete cure as a unit of effectiveness. A simplified cost-effectiveness
      analysis was conducted using complete cure rates from randomized, blinded
      clinical trials involving at least 50 participants. Trials were identified by
      searching the literature, manually searching for review articles, and reviewing
      medication package inserts. For each trial that met the entry criteria, three
      levels of cost were used to calculate medication cost per complete cure:
      commercial price, average wholesale price, and Veterans Affairs pharmacy price.
      In addition, a computerized economic model was used to determine total cost per
      complete cure, including all medical costs. The most cost-effective treatments
      were those that involved terbinafine: pulse, continuous, or in combination with
      other agents. Itraconazole, griseofulvin, and fluconazole were less cost
      effective. Ciclopirox nail lacquer was at least three times more expensive than
      all other agents when evaluating total costs per complete cure. Overall, the
      lowest cost per complete cure resulted from terbinafine treatment, with most
      evidence supporting 3 months of continuous therapy.

PMID- 16415283
TI  - Treatment for simple plantar verrucae: monochloroacetic acid and 10% formaldehyde
      versus 10% formaldehyde alone.
AB  - Verrucae are small, benign, highly vascular epithelial neoplasms that occur
      singly or in a multiple presentation. Plantar verrucae are usually caused by
      infection with human papillomavirus types 1, 2, and 4. A clinical trial was
      conducted to assess the safety and efficacy of monochloroacetic acid and 10%
      formaldehyde versus 10% formaldehyde alone in the treatment of simple plantar
      verrucae. Of 57 patients enrolled in the study, 26 were in the monochloroacetic
      acid and 10% formaldehyde group and 31 were in the 10% formaldehyde alone group.
      The overall cure rate for this population was 61.4%. There was no statistically
      significant difference in the cure rate between treatment groups.

PMID- 16415284
TI  - Synovial chondromatosis of the subtalar joint and tenosynovial chondromatosis of
      the posterior ankle.
AB  - Synovial chondromatosis is a rare, generally benign condition characterized by
      the formation of multiple cartilaginous nodules in the synovium of joints and
      occasionally on the tendon sheath or bursae. If the nodules are intra-articular,
      the condition is referred to as synovial chondromatosis; if extra-articular,
      tenosynovial chondromatosis. This space-occupying lesion can lead to chronic pain
      and limit the function of involved joints. We report a case of synovial
      chondromatosis involving the subtalar joint and tenosynovial chondromatosis
      involving the posterior ankle and review current definitions of this uncommon
      lower-extremity condition.

PMID- 16415285
TI  - Stress fractures of the lesser metatarsals after a Wilson osteotomy for
      correction of hallux valgus deformity.
AB  - This article describes a patient with lesser-metatarsal stress fractures
      resulting from an oblique Wilson displacement first metatarsal osteotomy. The
      shortening of the first metatarsal forces the lesser metatarsals to bear the
      weight previously borne by the first ray and increases the compression stress on
      the adjacent metatarsal heads. The proximal displacement of the osteotomy must be
      minimized in order to limit the risk of stress fracture of the lesser
      metatarsals.

PMID- 16415286
TI  - Necrotizing fasciitis in a patient with type 2 diabetes mellitus.
AB  - Necrotizing fasciitis is a soft-tissue infection characterized by extensive
      necrosis of subcutaneous fat, neurovascular structures, and fascia. In general,
      fascial necrosis precedes muscle and skin involvement, hence its namesake.
      Initially, this uncommon and rapidly progressive disease process can present as a
      form of cellulitis or superficial abscess. However, the high morbidity and
      mortality rates associated with necrotizing fasciitis suggest a more serious,
      ominous condition. A delay in diagnosis can result in progressive advancement
      highlighted by widespread infection, multiple-organ involvement, and, ultimately,
      death. We present a case of limb salvage in a 52-year-old patient with type 2
      diabetes mellitus and progressive fascial necrosis. A detailed review of the
      literature is presented, and current treatment modalities are described.
      Aggressive surgical debridement, comprehensive medical management of the sepsis
      and comorbidities, and timely closure of the resultant wound or wounds are
      essential for a successful outcome.

PMID- 16415287
TI  - NuGen Fx bioabsorbable screws: a preliminary report of their use in foot surgery.
AB  - A single prospective group study in adults was performed using a new
      bioabsorbable screw, the NuGen Fx screw (Linvatec Biomaterials Ltd, Tampere,
      Finland). This multisite study included five sites and 50 patients (10 patients
      per site). The goal of this study was to evaluate the efficiency and safety of
      the NuGen Fx screw system in the fixation of osteotomies, arthrodeses, and
      fractures in the foot and ankle. We discuss our own results from 12 patients
      treated at the Kentucky Podiatric Residency Program at Norton Audubon Hospital,
      Louisville. The number of patients in the study, screw sizes, instrumentation,
      radiologic evaluation findings, and our overview of this implant are presented.

PMID- 16415288
TI  - Congenital absence of the lateral sesamoid.
AB  - Congenital absence of the lateral sesamoid is an extremely rare condition. We
      present a case of congenital absence of the lateral sesamoid in which magnetic
      resonance imaging was performed. The literature is reviewed regarding the
      clinical significance of this anomaly.

PMID- 16415289
TI  - Letter to the editor: Maggot therapy in "lower-extremity hospice" wound care.

PMID- 16415294
TI  - A 15-ketosterol is a liver X receptor ligand that suppresses sterol-responsive
      element binding protein-2 activity.
AB  - Hypercholesterolemia is a major risk factor for coronary artery disease.
      Oxysterols are known to inhibit cholesterol biosynthesis and have been explored
      as potential antihypercholesterolemic agents. The ability of 3beta-hydroxy-5alpha
      cholest-8(14)-en-15-one (15-ketosterol) to lower non-HDL cholesterol has been
      demonstrated in rodent and primate models, but the mechanisms of action remain
      poorly understood. Here we show in a coactivator recruitment assay and
      cotransfection assays that the 15-ketosterol is a partial agonist for liver X
      receptor-alpha and -beta (LXRalpha and LXRbeta). The binding affinity for the
      LXRs was comparable to those of native oxysterols. In a macrophage cell line of
      human origin, the 15-ketosterol elevated ATP binding cassette transporter ABCA1
      mRNA in a concentration-dependent fashion with a potency similar to those of
      other oxysterols. We further found that in human embryonic kidney HEK 293 cells,
      the 15-ketosterol suppressed sterol-responsive element binding protein processing
      activity and thus inhibited mRNA expression of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase, LDL receptor, and PCSK9. Our data thus provide a molecular
      basis for the hypocholesterolemic activity of the 15-ketosterol and further
      suggest its potential antiatherosclerotic benefit as an LXR agonist.

PMID- 16415295
TI  - Maturation of human neutrophil phagosomes includes incorporation of molecular
      chaperones and endoplasmic reticulum quality control machinery.
AB  - A Human neutrophils are an essential component of the innate immune response.
      Although significant progress has been made toward understanding mechanisms of
      phagocytosis and microbicidal activity, a comprehensive analysis of proteins
      comprising neutrophil phagosomes has not been conducted. To that end, we used
      subcellular proteomics to identify proteins associated with human neutrophil
      phagosomes following receptor-mediated phagocytosis. Proteins (n = 411 spots)
      resolved from neutrophil phagosome fractions were identified by MALDI-TOF MS
      and/or LC-MS/MS analysis. Those associated with phagocytic vacuoles originated
      from multiple subcellular compartments, including the cytosol, plasma membrane,
      specific and azurophilic granules, and cytoskeleton. Unexpectedly several enzymes
      typically associated with mitochondria were identified in phagosome fractions.
      Furthermore proteins characteristic of the endoplasmic reticulum, including 11
      molecular chaperones, were resolved from phagosome preparations. Confocal
      microscopy confirmed that proteins representing these major subcellular
      compartments were enriched on phagosomes of intact neutrophils. Notably calnexin
      and glucose-regulated protein 78 co-localized with gp91(phox) in human
      neutrophils and were thus likely delivered to phagosomes by fusion of specific
      granules. We conclude that neutrophil phagosomes have heretofore unrecognized
      complexity and function, which includes potential for antigen processing events.

PMID- 16415296
TI  - Quantitative proteomic comparison of rat mitochondria from muscle, heart, and
      liver.
AB  - Mitochondria, through oxidative phosphorylation, are the primary source of energy
      production in all tissues under aerobic conditions. Although critical to life,
      energy production is not the only function of mitochondria, and the composition
      of this organelle is tailored to meet the specific needs of each cell type. As an
      organelle, the mitochondrion has been a popular subject for proteomic analysis,
      but quantitative proteomic methods have yet to be applied to tease apart subtle
      differences among mitochondria from different tissues or muscle types. Here we
      used mass spectrometry-based proteomics to analyze mitochondrial proteins
      extracted from rat skeletal muscle, heart, and liver tissues. Based on 689
      proteins identified with high confidence, mitochondria from the different tissues
      are qualitatively quite similar. However, striking differences emerged from the
      quantitative comparison of protein abundance between the tissues. Furthermore we
      applied similar methods to analyze mitochondrial matrix and intermembrane space
      proteins extracted from the same mitochondrial source, providing evidence for the
      submitochondrial localization of a number of proteins in skeletal muscle and
      liver. Several proteins not previously thought to reside in mitochondria were
      identified, and their presence in this organelle was confirmed by protein
      correlation profiling. Hierarchical clustering of microarray expression data
      provided further evidence that some of the novel mitochondrial candidates
      identified in the proteomic survey might be associated with mitochondria. These
      data reveal several important distinctions between mitochondrial and
      submitochondrial proteomes from skeletal muscle, heart, and liver tissue sources.
      Indeed approximately one-third of the proteins identified in the soluble
      fractions are associated predominantly to one of the three tissues, indicating a
      tissue-dependent regulation of mitochondrial proteins. Furthermore a small
      percentage of the mitochondrial proteome is unique to each tissue.

PMID- 16415297
TI  - Hospital care for children in developing countries: clinical guidelines and the
      need for evidence.

PMID- 16415298
TI  - Another case of missing dentures.

PMID- 16415299
TI  - Six month outcome of extremely old (> or = 95 years) trauma patients.

PMID- 16415300
TI  - Platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment during
      saphenous vein graft stenting: differential effects after randomization to
      occlusion or filter-based embolic protection.
AB  - AIMS: Although embolic protection devices reduce complications during saphenous
      vein graft (SVG) stenting, adverse events still occur in approximately 10% of
      patients. IIb/IIIa antagonists have not been proven effective during SVG
      intervention. We hypothesized that adjunctive use of these agents might enhance
      the efficacy of embolic protection devices. METHODS AND RESULTS: In the
      prospective, multicentre FilterWire EX Randomized Evaluation trial, 651 patients
      undergoing SVG stenting were randomized to either filter-based FilterWire EX or
      balloon occlusion/aspiration GuardWire embolic protection devices. IIb/IIIa
      inhibitor use was at the discretion of the investigator, with randomization
      stratified by intended use. Patients pre-selected for IIb/IIIa inhibitor use (n =
      345) had higher baseline risk, with increased 30-day major adverse cardiac events
      (MACE, 13.0 vs. 8.0%, P = 0.03). GuardWire assigned patients treated with
      IIb/IIIa inhibitors had higher 30-day MACE compared with those not treated with
      IIb/IIIa inhibitors (16.0 vs. 6.3%, P = 0.007). In contrast, MACE in high-risk
      FilterWire patients treated with IIb/IIIa inhibitors were similar to their lower
      risk, untreated counterparts (9.9 vs. 9.5%, P = 0.89). Multivariable analysis
      detected a borderline significant (P = 0.056) interaction for lower MACE between
      FilterWire and IIb/IIIa inhibitor use. Adjustment by the propensity to use
      IIb/IIIa inhibitors resulted in a significant (P = 0.023) interaction for lower
      MACE rates. IIb/IIIa inhibition in conjunction with FilterWire was associated
      with less abrupt closure, no reflow, or distal embolization. CONCLUSION: IIb/IIIa
      antagonists may improve procedural outcome during SVG stenting in high risk
      patients, utilizing filter-based embolic protection devices.

PMID- 16415301
TI  - Coronary artery ectasias: imaging, functional assessment and clinical
      implications.
AB  - Coronary artery ectasia is a relatively common entity characterized by
      inappropriate dilatation of the coronary vasculature. The exact mechanism of its
      development is unknown, but evidence suggests a combination of genetic
      predisposition, common risk factors for coronary artery disease and abnormal
      vessel wall metabolism. It frequently coexists with aneurysms elsewhere, mostly
      involving the aorta. In this review, the flow disturbances that are associated
      with this condition and the imaging modalities, which can be used for diagnosis
      and prospective follow-up are described. The prognosis of coronary ectasias is
      controversial and prospective studies focusing on conservative or invasive
      strategies to prevent cardiac complications are needed.

PMID- 16415302
TI  - Does tibolone exacerbate atherosclerosis?

PMID- 16415303
TI  - Classification of atrial fibrillation.

PMID- 16415305
TI  - Distinct glycoform ratios of protease resistant prion protein associated with
      PRNP point mutations.
AB  - Inherited prion diseases are neurodegenerative disorders caused by autosomal
      dominant mutations in the human prion protein gene (PRNP). Kindred with inherited
      prion disease can show remarkable phenotypic variability that has yet to be
      explained. Here we report analysis of protease resistant disease-related prion
      protein (PrP(Sc)) isoforms from a range of inherited prion disease cases (point
      mutations P102L, D178N, E200K and 2-, 4- and 6-octapeptide repeat insertions) and
      show that the glycoform ratios of PrP(Sc) associated with PRNP point mutations
      are distinct from those observed in sporadic, iatrogenic and variant Creutzfeldt
      Jakob disease. Patients with the same PRNP mutation can also propagate PrP(Sc)
      with distinct conformations. These data extend the spectrum of recognized PrP(Sc)
      types seen in human prion diseases and provide further insight into the
      generation of diverse clinicopathological phenotypes associated with inherited
      prion disease.

PMID- 16415304
TI  - The effect of tibolone and continuous combined conjugated equine oestrogens plus
      medroxyprogesterone acetate on progression of carotid intima-media thickness: the
      Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study.
AB  - AIMS: At the time of the design of the Osteoporosis Prevention and Arterial
      effects of tiboLone (OPAL) study in 1996, oral hormone therapy (HT) was assumed
      to reduce cardiovascular risk. The evidence mainly came from the effects of
      combined conjugated equine oestrogens plus medroxyprogesterone acetate (CEE/MPA)
      therapy. Other HT regimes had not been studied widely. Tibolone, a selective
      tissue oestrogenic activity regulator, has several effects on cardiovascular risk
      factors, one of which is HDL lowering. Because the overall effect of tibolone on
      cardiovascular risk was unknown, the OPAL study was designed. METHODS AND
      RESULTS: The OPAL study was a three-arm, randomized, placebo-controlled, double
      blind study to determine the effect of tibolone (2.5 mg daily) and of CEE/MPA
      (0.625/2.5 mg daily) over 3 years on progression of carotid intima-media
      thickness (CIMT) in 866 healthy post-menopausal women. The women were recruited
      from six US and five European centres. The primary outcome was change in mean
      common CIMT. Annual common CIMT progression rates in the tibolone and CEE/MPA
      groups were higher than in the placebo group: 0.0077 mm [95% confidence interval
      (CI) 0.0051-0.0103] in the tibolone group, 0.0074 mm (0.0048-0.0099) in the
      CEE/MPA group, and 0.0035 mm (0.009-0.0061) in the placebo group. The differences
      with placebo (0.0042 mm/year for tibolone and 0.0039 mm/year for CEE/MPA) were
      statistically significant. HDL cholesterol increased in CEE/MPA group and was
      lowered in the tibolone group. CONCLUSION: Both tibolone and CEE/MPA showed
      increased progression of common CIMT. Translation of the increased common CIMT
      progression of the CEE/MPA group into cardiovascular disease risk could not fully
      explain the observed increased cardiovascular risk as observed in the Women's
      Health Initiative study. This suggests that the net effect of tibolone and
      CEE/MPA on cardiovascular events may depend on the combined effects on the
      arterial wall, clotting factors, and possibly inflammation.

PMID- 16415306
TI  - Disgust-specific impairment of facial expression recognition in Parkinson's
      disease.
AB  - There is contradictory evidence regarding whether the impairments of the
      recognition of emotional facial expressions in Parkinson's disease are specific
      to certain emotions such as disgust and fear. Generally, neurological case
      reports on emotion-specific impairments have been suspected of being confounded
      with the factor of task difficulty. Using a refined assessment method in which
      the difficulty factors were controlled by means of mixed facial expressions and
      item response theory, we attempted to clarify whether Parkinson's disease
      disproportionately impaired the recognition of specific emotions. We studied 14
      patients with Parkinson's disease and 39 healthy controls who were matched in
      terms of gender, age, years of education and intelligence quotient. Whereas the
      refined method revealed that the patients with Parkinson's disease displayed
      significantly lower scores in disgust recognition alone, conventional methods
      failed to detect this impairment. In addition, control measures including face
      recognition abilities did not statistically explain the impairment observed in
      the patients. The results indicate that Parkinson's disease can indeed
      selectively impair the recognition of facial expressions of disgust; this
      provides concrete evidence for emotion-specific impairments that sufficiently
      withstands criticisms regarding the difficulty artefacts. Furthermore, the
      results support the proposed role of the basal ganglia-insula system in disgust
      recognition. This study effectively demonstrates the benefits of refining
      neuropsychological assessment by taking advantage of the modern psychometric
      theory.

PMID- 16415307
TI  - Skin denervation and cutaneous vasculitis in systemic lupus erythematosus.
AB  - To understand the clinical significance and mechanisms of cutaneous denervation
      in systemic lupus erythematosus (SLE), we assessed intraepidermal nerve fibre
      (IENF) density of the distal leg in 45 SLE patients (4 males and 41 females, aged
      38.4 +/- 13.6 years) and analysed its correlations with pathology, lupus
      activity, sensory thresholds and electrophysiological parameters. Compared with
      age- and gender-matched control subjects, SLE patients had lower IENF densities
      (3.08 +/- 2.17 versus 11.27 +/- 3.96 fibres/mm, P < 0.0001); IENF densities were
      reduced in 38 patients (82.2%). Pathologically, 11 patients (24.4%) were found to
      have definite cutaneous vasculitis; the severity and extent of cutaneous
      vasculitis were correlated with IENF densities. Patients with active lupus had
      even lower IENF densities than those with quiescent lupus (1.86 +/- 1.37 versus
      4.15 +/- 2.20 fibres/mm, P = 0.0002). By linear regression analysis, IENF
      densities were negatively correlated with the SLE disease activity index (r =
      0.527, P = 0.0002) and cumulative episodes of lupus flare-up within 2 years
      before the skin biopsy (r = 0.616, P = 0.0014). Clinically, skin denervation was
      present not only in the patients with sensory neuropathy but also in the patients
      with neuropsychiatric syndrome involving the CNS. SLE patients had significantly
      elevated warm threshold temperatures (P = 0.003) and reduced cold threshold
      temperatures (P = 0.048); elevated warm threshold temperatures were associated
      with the reduced IENF densities (P = 0.032). In conclusion, cutaneous vasculitis
      and lupus activities underlie skin denervation with associated elevation of
      thermal thresholds as a major manifestation of sensory nerve injury in SLE.

PMID- 16415308
TI  - Natural history of multiple sclerosis: a unifying concept.
AB  - Multiple sclerosis can follow very different patterns of evolution and variable
      rates of disability accumulation. This raises the issue whether it represents one
      or several distinct diseases. We assessed demographic and clinical
      characteristics in 1844 patients with multiple sclerosis that we categorized
      according to the classification of Lublin and Reingold (1996) into 1066 (58%)
      relapsing-remitting, 496 (27%) secondary progressive, 109 (6%) progressive
      relapsing and 173 (9%) primary progressive cases of multiple sclerosis. Relapsing
      remitting and secondary progressive cases shared similar age at disease onset
      (median = 28.7 versus 29.5 years; P = 0.21), initial symptoms of the relapsing
      remitting phase, degree of recovery from the first neurological episode, and time
      from the first to the second episode. By contrast, disease duration was twice as
      long in secondary progressive than in relapsing-remitting cases (mean +/- SD =
      17.6 +/- 9.6 versus 8.7 +/- 8.6 years; P < 0.001). Progressive relapsing and
      primary progressive cases were essentially similar in their clinical
      characteristics. In patients experiencing a progressive course, median age at
      onset of progressive phase was similar in secondary progressive cases and in
      cases who were progressive from onset (39.1 versus 40.1 years; P = 0.47). The
      proportion of cases with superimposed relapses during progression was
      approximately 40% in both categories. Finally, the 1562 patients with an
      exacerbating-remitting initial course and the 282 patients with a progressive
      initial course of the disease were essentially similar with respect to the time
      course of disability accumulation from assignment to a given disability score,
      and the age at assignment of disability landmarks. These observational data
      suggest that the clinical phenotype and course of multiple sclerosis are age
      dependent. Relapsing-remitting disease can be regarded as multiple sclerosis in
      which insufficient time has elapsed for the conversion to secondary progression;
      secondary progressive forms as relapsing-remitting multiple sclerosis that has
      'grown older'; and progressive from onset cases as multiple sclerosis 'amputated'
      from the usual preceding relapsing-remitting phase. Times to reach disability
      milestones, and ages at which these landmarks are reached, follow a predefined
      schedule not obviously influenced by relapses, whenever they may occur, or by the
      initial course of the disease, whatever its phenotype. This leads to a unifying
      concept of the disease in which primary and secondary progression might be
      regarded as essentially similar. From the clinical and statistical positions,
      multiple sclerosis might be considered as one disease with different clinical
      phenotypes rather than an entity encompassing several distinct diseases-the
      position of complexity rather than true heterogeneity.

PMID- 16415309
TI  - Age at disability milestones in multiple sclerosis.
AB  - Many efforts have been devoted to the description of the prognosis of multiple
      sclerosis and its possible influential factors in terms of time to reach
      disability milestones. By contrast, the age at which patients with multiple
      sclerosis reach these milestones has not yet stirred much interest. We have
      tested the hypothesis whether the prognosis of multiple sclerosis depends on the
      current age of patients and the initial course of the disease. We have assessed
      disease onset and course, and assignment of scores of irreversible disability in
      1844 patients with multiple sclerosis. We have used three scores on the Kurtzke
      Disability Status Scale as benchmarks of disability accumulation: DSS 4 (limited
      walking but without aid), DSS 6 (walking with unilateral aid) and DSS 7
      (wheelchair-bound). We used Kaplan-Meier analyses to estimate the age of the
      patients at assignment of disability milestones. The possible influence of the
      initial course of multiple sclerosis and of other clinical variables early
      assessable in the disease on these outcome measures was also studied, using the
      Kaplan-Meier curves for univariate analyses and Cox models for multivariate
      analyses. For the 1844 patients, median ages at time of assignment of
      irreversible disability were 44.3 years (95% CI 43.3-45.2) for a score of DSS 4,
      54.7 years (95% CI 53.5-55.8) for DSS 6 and 63.1 years (95% CI 61.0-65.1) for DSS
      7. These results were essentially similar whether the initial course of multiple
      sclerosis was exacerbating-remitting or progressive, and whatever the initial
      symptomatology. Females reached disability milestones at an older age than males.
      The most influential clinical factor was age at clinical onset of multiple
      sclerosis: the younger the onset, the younger the age at assignment of disability
      milestones. Therefore, prognosis in multiple sclerosis appears, at least to some
      extent, as age-dependent and not substantially affected by the initial course, be
      it exacerbating-remitting or progressive. Aside acute focal recurrent
      inflammation and diffuse chronic neurodegeneration, accelerated ageing-related
      mechanisms may operate in the central nervous system of multiple sclerosis
      patients.

PMID- 16415310
TI  - Combined use of Bispectral Index and A-Line Autoregressive Index to assess anti
      nociceptive component of balanced anaesthesia during lumbar arthrodesis.
AB  - BACKGROUND: This study evaluated the A-Line Autoregressive Index (AAI) response
      to surgical stimulation during lumbar arthrodesis, as an estimate of the anti
      nociceptive component of a Bispectral Index (BIS) guided anaesthesia combined
      with epidural analgesia. METHODS: An epidural catheter was inserted in 23
      patients allocated randomly to receive ropivacaine plus clonidine (Group R) or
      normal saline (Group S) epidurally. General anaesthesia was induced with
      propofol, cis-atracurium and a remifentanil infusion that was stopped 3 min after
      tracheal intubation, and maintained using sevoflurane to keep BIS at 50 (range 40
      60). Mean arterial pressure, heart rate, end-tidal sevoflurane, BIS and AAI were
      analysed from 2 min before to 17 min after surgical incision. RESULTS: While BIS
      was maintained at 50, AAI significantly increased from a 2 min averaged value of
      12 (4) to 21 (7) in Group S within the first 5 min after surgical incision, but
      did not change in Group R. Maximum AAI values reached during the study period
      were significantly higher in Group S than in Group R [38 (12) and 27 (10),
      respectively]. Binary logistic regression analysis allowed the calculation of AAI
      threshold values above which the probability of predominant nociception over anti
      nociception was higher than 95%. At 1 MAC sevoflurane concentration, a 2 min
      averaged AAI of 35 or an AAI peak value of 62 were associated with such a
      probability. CONCLUSIONS: During a BIS-guided constant level of hypnosis, AAI
      response to the onset of surgical stimulation significantly differs according to
      the analgesic regimen. Further studies are needed to refine the estimation of
      sensitivity and specificity of this variable in assessing the balance between
      nociception and anti-nociception during general anaesthesia.

PMID- 16415311
TI  - Comparison of efficacy of oxybutynin and tolterodine for prevention of catheter
      related bladder discomfort: a prospective, randomized, placebo-controlled, double
      blind study.
AB  - BACKGROUND: Bladder discomfort related to intraoperative catheterization of
      urinary bladder is a distressing symptom and more so in patients awakening from
      anaesthesia. These symptoms are similar to symptoms of overactive bladder.
      Muscarinic receptor antagonists have been reported to be effective in the
      treatment of overactive bladder. This study was therefore undertaken to evaluate
      the efficacy of oxybutynin and tolterodine in preventing catheter related bladder
      discomfort. METHODS: Two hundred and thirty-four consecutive adult patients, ASA
      I and II, of either sex, undergoing elective percutaneous nephrolithotomy surgery
      requiring urinary bladder catheterization were randomized into three equal groups
      of 78 each. Group C (control) received placebo, Group O (oxybutynin) received
      oxybutynin 5 mg and Group T (tolterodine) received tolterodine 2 mg orally 1 h
      before surgery. After induction of anaesthesia patients were catheterized with a
      16 Fr Foley's catheter and the balloon was inflated with 10 ml distilled water.
      The bladder discomfort was assessed at 0, 1, 2 and 6 h after patient's arrival in
      the post-anaesthesia care unit. Severity of bladder discomfort was graded as
      mild, moderate and severe. RESULTS: Incidence of bladder discomfort observed in
      the control group was higher, i.e. 58% (45/78), compared with oxybutynin and
      tolterodine groups where it was 35% (28/78) and 33% (26/78), respectively
      (P<0.05). Significant reduction in the severity of bladder discomfort was also
      observed after oxybutynin and tolterodine therapy compared with control (P<0.05).
      CONCLUSION: Pretreatment with either oxybutynin or tolterodine reduces the
      incidence and severity of catheter related bladder discomfort.

PMID- 16415312
TI  - Adenosine-induced cardiac arrest and EEG changes in patients with thoracic aorta
      endovascular repair.
AB  - BACKGROUND: We studied haemodynamic and metabolic variables, and cerebral
      function after cardiac arrest induced by high dose of adenosine in patients
      undergoing thoracic aorta endovascular repair. METHODS: Arterial blood pressure,
      blood gas values and EEG were recorded continuously in 15 patients undergoing
      anaesthesia (isoflurane) for endovascular thoracic aorta repair. Cardiac arrest
      was induced by different doses of adenosine (Adrekar, Sanofi-Synthelabo, Berlin,
      Germany; 0.4-1.8 mg kg(-1) body weight). Serum concentrations of neurone-specific
      enolase (NSE) were determined before and after stent graft implantation.
      Neurological function was assessed before and after surgery. RESULTS: After
      adenosine, the heart beat stopped immediately for 18-58 s in close relation to
      the adenosine dose. EEG power was significantly reduced to -57%, but reached
      normal values within 5 min after cardiac arrest. In particular, the fast alpha-
      and beta-EEG-frequencies sensitively reflected patients' EEG activity during the
      procedure. No intraoperative increases in NSE concentrations, and no neurological
      dysfunctions after surgery, were observed. CONCLUSION: After adenosine-induced
      cardiac arrest, changes in haemodynamic variables and EEG power spectra reversed
      completely within 1 and 5 min, respectively, without persistent brain dysfunction
      after stent graft implantation.

PMID- 16415313
TI  - The LMA CTrach, a new laryngeal mask airway for endotracheal intubation under
      vision: evaluation in 100 patients.
AB  - BACKGROUND: The LMA CTrach is a new laryngeal mask system consisting of an LMA
      CTrach Airway with integrated fibreoptic channels, and a detachable LMA CTrach
      Viewer. This system enables viewing of the larynx and aids endotracheal
      intubation through a laryngeal mask airway. Method. We used and evaluated this
      system in 100 adult patients undergoing general anaesthesia for elective surgery.
      Our primary outcomes were the success rates of LMA CTrach Airway insertion and
      endotracheal intubation with this system. RESULTS: We were able to insert the LMA
      CTrach Airway in and to ventilate all 100 patients. We were successful in
      endotracheal intubation, either under vision or blind, in 96 patients. We were
      able to view the larynx in 84 patients, but the quality of the best view obtained
      was very variable. The median (inter quartile range) time for the complete
      intubation process was 166 (114-233) s. The system allowed nearly continuous
      ventilation and oxygenation during the process. CONCLUSIONS: The LMA CTrach
      system has potential advantages over the LMA Fastrach system, including the
      ability to align the LMA outlet with the larynx and a high first intubation
      attempt success rate. However, it was difficult to view the larynx with the LMA
      CTrach compared with direct laryngoscopy, and expectations must be moderated.

PMID- 16415314
TI  - Relationship between perioperative troponin elevation and other indicators of
      myocardial injury in vascular surgery patients.
AB  - BACKGROUND: In 2000 the European Society of Cardiology and the American College
      of Cardiology published a consensus document revising the definition of
      myocardial infarction. The usefulness of this revised definition has been
      challenged. It has been suggested that, rather than any release of cardiac
      troponin being potentially diagnostic of myocardial infarction, a diagnostic
      threshold consistent with significant myocardial injury should be defined.
      METHODS: We studied 65 patients undergoing elective major vascular surgery to
      examine the relationship between the magnitude of cardiac troponin I (cTnI) and
      creatine kinase MB fraction (CK-MB) release and clinical signs or symptoms of
      myocardial injury. cTnI and CK-MB concentrations were measured preoperatively and
      on the first 4 postoperative days using the ACCESS assay (Beckmann). Patients
      were considered to have suffered a perioperative myocardial infarction if they
      had either symptoms or ECG changes consistent with this diagnosis, together with
      cTnI release. RESULTS: Peak postoperative cTnI concentrations above the lower
      detection limit of the ACCESS assay (0.06 microg litre(-1)) occurred in 26
      patients. Eight of these patients displayed symptoms or ECG changes consistent
      with myocardial injury. A cTnI level greater than 0.68 microg litre(-1) was found
      to be consistent with the clinical diagnosis of myocardial infarction. The
      optimal cut-off for the diagnosis of MI using CK-MB was 40.4 microg litre(-1).
      CONCLUSIONS: These data suggest that further studies are required to define the
      optimal cardiac troponin diagnostic threshold for the diagnosis of myocardial
      infarction in the non-cardiac surgery population.

PMID- 16415316
TI  - Stimulation induced variability of pulse plethysmography does not discriminate
      responsiveness to intubation.
AB  - BACKGROUND: Hypnotic depth but not haemodynamic response to painful stimulation
      can be measured with various EEG-based anaesthesia monitors. We evaluated the
      variation of pulse plethysmography amplitude induced by an electrical tetanic
      stimulus (PPG variation) as a potential measure for analgesia and predictor of
      haemodynamic responsiveness during general anaesthesia. METHODS: Ninety-five
      patients, ASA I or II, were randomly assigned to five groups [Group 1: bispectral
      index (BIS) (range) 40-50, effect site remifentanil concentration 1 ng ml(
      1);Group 2: BIS 40-50, remifentanil 2 ng ml(-1); Group 3: BIS 40-50, remifentanil
      4 ng ml(-1); Group 4: BIS 25-35, remifentanil 2 ng ml(-1); Group 5: BIS 55-65,
      remifentanil 2 ng ml(-1)]. A 60 mA tetanic stimulus was applied for 5 s on the
      ulnar nerve. From the digitized pulse oximeter wave recorded on a laptop
      computer, linear and non-linear parameters of PPG variation during the 60 s
      period after stimulation were computed. The haemodynamic response to subsequent
      orotracheal intubation was recorded. The PPG variation was compared between
      groups and between responders and non-responders to intubation (anova). Variables
      independently predicting the response were determined by logistic regression.
      RESULTS: The probability of a response to tracheal intubation was 0.77, 0.47,
      0.05, 0.18 and 0.52 in Groups 1-5, respectively (P<0.03). The PPG variability was
      significantly higher in responders than in non-responders but it did not improve
      the prediction of the response to tracheal intubation based on BIS level and
      effect site remifentanil concentration. CONCLUSION: Tetanic stimulation induced
      PPG variation does not reflect the analgesic state in a wide clinical range of
      surgical anaesthesia.

PMID- 16415315
TI  - Pharmacokinetics of S(+) ketamine derived from target controlled infusion.
AB  - BACKGROUND: A computer controlled infusion device for S(+) ketamine was used in
      combination with a Diprifusor device to provide anaesthesia for 20 ASA I or II
      patients undergoing elective colonoscopy. The aim of the study was to assess the
      performance of the pharmacokinetic model for S(+) ketamine used in the delivery
      algorithm of the device. RESULTS: It was observed that during the first 30 min of
      infusion there was systematic underprediction by the delivery system of the
      measured levels of S(+) ketamine. New pharmacokinetic constants were derived from
      the observed data which provided, on pharmacokinetic simulation, improved
      prediction of the measured values of S(+) ketamine. Prospective application of
      this modified model for S(+) ketamine in a further nine study patients was
      performed and the pharmacokinetic performance of the model was reassessed. The
      data from all 29 patients was subsequently used to calculate the population
      distribution of S(+) ketamine clearance. The distribution was found to be normal
      only in the logarithmic domain. In the normal domain the mode of S(+) ketamine
      clearance was found to be 35.8 ml kg(-1) min(-1) with 5 and 95% confidence limits
      of, respectively, 11.5 and 111.1 ml kg(-1) min(-1). CONCLUSION: It was necessary
      to modify the original published pharmacokinetic parameters incorporated into the
      S(+) ketamine delivery system in order to simulate improved PK performance during
      short procedures (<1 h duration) where propofol was concurrently administered.
      This improved performance was confirmed in a further prospective study.

PMID- 16415317
TI  - Anaesthetic management of thoracopagus twins with complex cyanotic heart disease
      for cardiac assessment: special considerations related to ventilation and cross
      circulation.
AB  - We describe the anaesthetic management of a pair of thoracopagus twins of 14
      months of age undergoing complex cardiac evaluation. Synchronous ventilation of
      the twins, needed for the ECG-gated magnetic resonance imaging-angiography, was
      achieved through a Carlens (Y) adaptor during procedures and transport. The
      complex logistical implications are obvious. We also describe the first use of
      bispectral index monitor for detection of cross-circulation in conjoint twins.

PMID- 16415318
TI  - The carina as a radiological landmark for central venous catheter tip position.
AB  - BACKGROUND: Many publications, including the instructions accompanying central
      venous catheters, state that it is negligent to site the catheter tip in the
      right atrium. If the catheter tip is above the carina on a post-procedure
      radiograph then it is generally accepted that the catheter lies outside the right
      atrium. It is also recommended that the catheter tip should lie in the long axis
      of the superior vena cava without acute abutment to the vein wall. We performed a
      retrospective audit of the position of central venous catheter tips on routine
      post-procedure chest radiographs in intensive care unit patients, to see if these
      potentially conflicting requirements had been met. METHODS: We identified 213
      central venous catheters suitable for analysis, within a study population of 200
      consecutive cases. We measured the distance of the central venous catheter tip
      above or below the carina and the angle of the central venous catheter tip to the
      vertical (a surrogate marker for the angle of abutment of the tip to the
      approximately vertical superior vena cava wall). RESULTS: For right-sided
      catheters there was a high (74/163) number placed with their tips below the
      carina, but a very low number (4/163) with their tips at a steep (>40 degrees )
      angle to the vertical. For left-sided catheters very few (7/50) were placed with
      their tips below the carina, but for those 43 sited above the carina most could
      be considered to be in suboptimal positions. This was because they were either
      too high and had not even crossed the midline (9), or had an acute angle (>40
      degrees ) between the tip and the vertical (27). CONCLUSIONS: We suggest that for
      left-sided catheters placement of the tip below the carina is more likely to
      result in a satisfactory placement.

PMID- 16415319
TI  - The classic laryngeal mask airway: a tried and tested airway. What now?

PMID- 16415320
TI  - Gabapentin: a new drug for postoperative pain?

PMID- 16415321
TI  - Migration of interscalene catheter--not proven.

PMID- 16415322
TI  - Relationship between bispectral index and effect-site EC(50) for propofol.

PMID- 16415323
TI  - Acute intracardiac right-to-left shunt in a patient with acute respiratory
      distress syndrome and shock successfully treated with nitric oxide.

PMID- 16415324
TI  - Successful weaning from mechanical ventilation after abdominal lipectomy and
      omentectomy in an obese patient with multiple rib fractures.

PMID- 16415325
TI  - Near misses with prefilled syringes.

PMID- 16415326
TI  - Complexity, simplicity, and epidemiology.

PMID- 16415327
TI  - Effects of perfluorooctanoic acid exposure during pregnancy in the mouse.
AB  - Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have
      wide commercial applications, has recently been detected in humans and wildlife.
      The current study characterizes the developmental toxicity of PFOA in the mouse.
      Timed-pregnant CD-1 mice were given 1, 3, 5, 10, 20, or 40 mg/kg PFOA by oral
      gavage daily from gestational day (GD) 1 to 17; controls received an equivalent
      volume (10 ml/kg) of water. PFOA treatment produced dose-dependent full-litter
      resorptions; all dams in the 40-mg/kg group resorbed their litters. Weight gain
      in dams that carried pregnancy to term was significantly lower in the 20-mg/kg
      group. At GD 18, some dams were sacrificed for maternal and fetal examinations
      (group A), and the rest were treated once more with PFOA and allowed to give
      birth (group B). Postnatal survival, growth, and development of the offspring
      were monitored. PFOA induced enlarged liver in group A dams at all dosages, but
      did not alter the number of implantations. The percent of live fetuses was lower
      only in the 20-mg/kg group (74 vs. 94% in controls), and fetal weight was also
      significantly lower in this group. However, no significant increase in
      malformations was noted in any treatment group. The incidence of live birth in
      group B mice was significantly lowered by PFOA: ca. 70% for the 10- and 20-mg/kg
      groups compared to 96% for controls. Postnatal survival was severely compromised
      at 10 or 20 mg/kg, and moderately so at 5 mg/kg. Dose-dependent growth deficits
      were detected in all PFOA-treated litters except the 1-mg/kg group. Significant
      delays in eye-opening (up to 2-3 days) were noted at 5 mg/kg and higher dosages.
      Accelerated sexual maturation was observed in male offspring, but not in females.
      These data indicate maternal and developmental toxicity of PFOA in the mouse,
      leading to early pregnancy loss, compromised postnatal survival, delays in
      general growth and development, and sex-specific alterations in pubertal
      maturation.

PMID- 16415328
TI  - Increasing exposure levels cause an abrupt change in the absorption and
      metabolism of acutely inhaled benzo(a)pyrene in the isolated, ventilated, and
      perfused lung of the rat.
AB  - The carcinogenic polycyclic aromatic hydrocarbons (PAHs) are active primarily at
      the site of entry to the body. Lung cancer following inhalation of PAH-containing
      aerosols such as tobacco smoke is one likely example. A suggested mechanism for
      this site preference is a slow passage of the highly lipophilic PAHs through the
      thicker epithelia of the conducting airways, accompanied by substantial local
      metabolism in airway epithelium. However, it is likely that the airway epithelium
      will become saturated with PAHs at surprisingly low exposure levels. The purpose
      of this research was to quantify the level of saturation for inhaled
      benzo(a)pyrene (BaP) in the isolated, perfused lung (IPL) of the rat. BaP was
      coated onto carrier particles of silica 3.5 microm diameter at three different
      levels. The DustGun aerosol generator was then used to deliver respectively 2.2,
      36, and 8400 ng of BaP to the IPL with the carrier particles in less than 1 min.
      For 77 min after the exposure, single-pass perfusate was collected from the
      lungs. Lungs were then removed and, with the perfusate, analyzed for BaP and
      metabolites. Results show that the absorption and metabolism of inhaled BaP in
      the lungs was highly dose dependent. At low exposure levels absorption of BaP in
      the mucosa was proportional to the concentration in the air/blood barrier and
      proceeded with substantial local metabolism. At higher exposure levels the
      capacity of the epithelium to dissolve and metabolize BaP became saturated, and
      the absorption rate remained constant until crystalline BaP had dissolved, and
      the process proceeded with much smaller fractions of BaP metabolites produced in
      the mucosa. This phenomenon may explain the well-known difficulties of inducing
      lung cancer in laboratory animals with inhalants containing carcinogenic PAHs,
      where similar lifespan exposures are used as humans may experience but with much
      higher dose rates.

PMID- 16415329
TI  - Unique gene expression and hepatocellular injury in the lipopolysaccharide
      ranitidine drug idiosyncrasy rat model: comparison with famotidine.
AB  - Rats cotreated with lipopolysaccharide (LPS) and ranitidine (RAN) but not LPS and
      famotidine (FAM) develop hepatocellular injury in an animal model of
      idiosyncratic drug reactions. Evaluation of liver gene expression in rats given
      LPS and/or RAN led to confirmation that the hemostatic system, hypoxia, and
      neutrophils (PMNs) are critical mediators in LPS/RAN-induced liver injury. We
      tested the hypothesis that unique gene expression changes distinguish LPS/RAN
      treated rats from rats given LPS or RAN alone and from those cotreated with
      LPS/FAM. Rats were treated with a nonhepatotoxic dose of LPS (44.4 x 10(6)
      endotoxin units/kg, iv) or its vehicle. Two hours thereafter they were given RAN
      (30 mg/kg, iv), FAM (either 6 mg/kg, a pharmacologically equi-efficacious dose,
      or 28.8 mg/kg, an equimolar dose, iv), or vehicle. They were killed 2 or 6 h
      after drug treatment for evaluation of hepatotoxicity (2 and 6 h) and liver gene
      expression (2 h only). At a time before the onset of hepatocellular injury,
      hierarchical clustering distinguished rats treated with LPS/RAN from those given
      LPS alone. 205 probesets were expressed differentially to a greater or lesser
      degree only in LPS/RAN-treated rats compared to LPS/FAM or LPS alone, which did
      not develop liver injury. These included VEGF, EGLN3, MAPKAPK-2, BNIP3, MIP-2,
      COX-2, EGR-1, PAI-1, IFN-gamma, and IL-6. Expression of these genes was confirmed
      by real-time PCR. Serum concentrations of MIP-2, PAI-1, IFN-gamma, and IL-6
      correlated with their respective gene expression patterns. Overall, the
      expression of several gene products capable of controlling requisite mediators of
      injury (i.e., hemostasis, hypoxia, PMNs) in this model were enhanced in livers of
      LPS/RAN-treated rats. Furthermore, enhanced expression of MAPKAPK-2 in RAN
      treated rats and its target genes in LPS/RAN-treated rats suggests that
      p38/MAPKAPK-2 signaling is a regulation point for enhancement of LPS-induced gene
      expression by RAN.

PMID- 16415330
TI  - Differential adaptation of two varieties of common bean to abiotic stress: I.
      Effects of drought on yield and photosynthesis.
AB  - The yield of 24 commercial varieties and accessions of common bean (Phaseolus
      vulgaris) has been determined at different sites in Chile and Bolivia.
      Statistical analysis was performed in order to characterize whether a particular
      variety was more or less stable in yield under different environmental
      conditions. Amongst these, two varieties have been identified for more detailed
      study: one variety has a higher than average yield under unstressed conditions
      but is strongly affected by stress, and another has a reduced yield under
      unstressed conditions but is less affected by stress. The contrasting rate of
      abscission of the reproductive organs under drought stress was clearly consistent
      with these differences. The more tolerant genotype shows a great deal of
      plasticity at the biochemical and cellular level when exposed to drought stress,
      in terms of stomatal conductance, photosynthetic rate, abscisic acid synthesis,
      and resistance to photoinhibition. By contrast, the former lacks such plasticity,
      but shows an enhanced tendency for a morphological response, the movement of
      leaves, which appears to be its principal response to drought stress.

PMID- 16415331
TI  - Differential adaptation of two varieties of common bean to abiotic stress: II.
      Acclimation of photosynthesis.
AB  - The photosynthetic characteristics of two contrasting varieties of common bean
      (Phaseolus vulgaris) have been determined. These varieties, Arroz and Orfeo,
      differ in their productivity under stress conditions, resistance to drought
      stress, and have distinctly different stomatal behaviour. When grown under
      conditions of high irradiance and high temperature, both varieties displayed
      evidence of photosynthetic acclimation at the chloroplast level-there was an
      increase in chlorophyll a/b ratio, a decreased content of Lhcb proteins, and an
      increased xanthophyll cycle pool size. Both varieties also showed reduced
      chlorophyll content on a leaf area basis and a decrease in leaf area. Both
      varieties showed an increase in leaf thickness but only Arroz showed the
      characteristic elongated palisade cells in the high light-grown plants; Orfeo
      instead had a larger number of smaller, rounded cells. Differences were found in
      stomatal development: whereas Arroz showed very little change in stomatal
      density, Orfeo exhibited a large increase, particularly on the upper leaf
      surface. It is suggested that these differences in leaf cell structure and
      stomatal density give rise to altered rates of photosynthesis and stomatal
      conductance. Whereas, Arroz had the same photosynthetic rate in plants grown at
      both low and high irradiance, Orfeo showed a higher photosynthetic capacity at
      high irradiance. It is suggested that the higher yield of Orfeo compared with
      Arroz under stress conditions can be explained, in part, by these cellular
      differences.

PMID- 16415332
TI  - Drought effects on carbon and nitrogen metabolism of pea nodules can be mimicked
      by paraquat: evidence for the occurrence of two regulation pathways under
      oxidative stresses.
AB  - Biological nitrogen fixation (BNF) is dramatically affected by environmental
      constraints such as water stress or heavy metals. It has been reported that these
      stresses induce the over-production of reactive oxygen species (ROS) and, in
      turn, oxidative stress that may be responsible for the above-mentioned BNF
      decline at the molecular level. Oxidative stress, occurring under different
      environmental stresses, has been widely related to physiological damage. However,
      a direct relationship between oxidative stress and the decline of BNF,
      independently from any other cellular damage resulting from adverse environmental
      situations, has yet to be demonstrated. In order to study the likely in vivo
      relationship between ROS and BNF inhibition in the legume-Rhizobium symbiosis,
      two paraquat (PQ) doses, 1 (LPQ) and 10 (HPQ) mmol m(-3), were applied to pea
      roots for 96 h in order to exacerbate ROS production. Whole-plant physiology and
      nodule metabolism parameters were determined every 24 h to monitor the evolution
      of plant responses to ROS. LPQ provoked BNF decline, which was preceded by a
      prior decrease in sucrose synthase (SS) activity. However, HPQ gave rise to a
      faster and more pronounced BNF inhibition, which coincided with a decline in SS
      and also with a reduction in leghaemoglobin (Lb) content. These results indicate
      a likely involvement of ROS in the effects of environmental stresses on BNF.
      Furthermore, these results support the occurrence of two regulation pathways for
      BNF under oxidative stress, one of these involving carbon shortage and the other
      involving Lb/oxygen flux.

PMID- 16415333
TI  - Physiological and molecular aspects of aspartate-derived amino acid metabolism
      during germination and post-germination growth in two maize genotypes differing
      in germination efficiency.
AB  - The Asp-derived amino acid pathway has been studied during the early stages of
      development in two maize genotypes, Io and F2, differing in germination
      efficiency and post-germination growth. In both genotypes expression of Ask2
      (monofunctional Asp-kinase-2), Akh1 and Akh2 (bifunctional Asp-kinase-homo-Ser
      dehydrogenase-1 and 2), increased throughout germination and post-germination
      growth, suggesting a developmental regulation, whereas Ask1 (monofunctional Asp
      kinase-1) was expressed constitutively. The major difference between Io and F2
      concerned genes encoding bifunctional enzymes, particularly Akh2, the expression
      of which was dramatically low in F2. 15N-Asp labelling showed differences in in
      vivo Asp-kinase activities between the genotypes studied. Asp flux through the
      Met/Thr branches was higher in Io than in F2, while the latter exhibited a higher
      flux of Asp through the Lys branch. Physiological results, together with the
      higher Akh2 expression in Io, suggest that bifunctional enzyme activity,
      favourable to Met/Thr, was higher in Io than in F2 and that the monofunctional
      pathway was boosted in F2 because of the lower competition by the bifunctional
      pathway, thus allowing for higher flux of Asp through the Lys branch. In
      conclusion, it is suggested that F2 germination and post-germination growth might
      have been partially inhibited due to a limitation in Met and Thr availability. A
      negative physiological effect related to Lys accumulation in F2 is also
      discussed.

PMID- 16415335
TI  - How not to be a doctor.

PMID- 16415334
TI  - Membrane-type matrix metalloproteinases and vascularization in human endometrium
      during the menstrual cycle.
AB  - Endometrial angiogenesis is essential for a vascularized receptive endometrium.
      Previously, we described that membrane type-3 metalloproteinase (MT3-MMP) is
      associated with endometrial angiogenesis in vitro. The association of MT-MMPs
      with endometrial angiogenesis in vivo is unknown. Therefore, this study analysed
      the presence of MT-MMPs in human endometrium and their correlation with
      neovascularization. RNA/protein expressions of the six MT-MMPs were determined in
      cultured endometrial cells. Vascularization parameters and MT-MMP expressions in
      vivo were evaluated by immunohistochemistry in serial endometrium sections. MT1-,
      MT2-, MT3- and MT4-MMP antigens were expressed in cultured endometrial
      endothelial cells. MT2-, MT3- and MT4-MMP were expressed by endothelium during
      the proliferative and secretory phase. Strikingly, these phases showed elevated
      vascularization, elevated total vascular surface in proliferative phases,
      elevated number of vessels in proliferative/late secretory phases and increased
      luminal surface in the proliferative phases. All MT-MMP antigens were expressed
      in various endometrial cell types in vivo, with decreased levels during the early
      secretory phase. In conclusion, all MT-MMPs are expressed in endometrium in a
      cycle-dependent pattern. The vascular expression of MT2-, MT3- and MT4-MMP
      correlated with angiogenic episodes of the cycle. Since MT2- and MT3-MMP are
      known to regulate tube formation, these findings support earlier in vitro data on
      the role of MT3-MMP in endometrial angiogenesis. Additionally, MT2-MMP appears to
      be associated with endometrial neovascularization also.

PMID- 16415336
TI  - Compliance with QUOROM and quality of reporting of overlapping meta-analyses on
      the role of acetylcysteine in the prevention of contrast associated nephropathy:
      case study.
AB  - OBJECTIVE: To appraise multiple systematic reviews on the same clinical topic,
      focusing on predictors and correlates of quality of reporting of meta-analysis
      (QUOROM) scores. DESIGN: Case study. SETTING: Reviews providing at least
      individual quantitative estimates on role of acetylcysteine in the prevention of
      contrast associated nephropathy. DATA SOURCES: PubMed, the database of abstracts
      of reviews of effects, and the Cochrane database of systematic reviews (updated
      March 2005). MAIN OUTCOME MEASURES: Funding, compliance with the QUOROM
      checklist, scores on the Oxman and Guyatt quality index, and authors'
      recommendations. RESULTS: 10 systematic reviews, published August 2003 to March
      2005, were included. Nine pooled events despite heterogeneity and five
      recommended routine use of acetylcysteine, whereas the remaining studies called
      for further research. Compliance with the 18 items on the QUOROM checklist was
      relatively high (median 16, range 11 to 17), although shorter manuscripts had
      significantly lower scores (R = 0.73; P = 0.016). Reviewers who reported previous
      not for profit funding were more likely to score higher on the Oxman and Guyatt
      quality index. No association was found between QUOROM and Oxman and Guyatt
      scores (R = -0.06; P = 0.86), mainly because of greater emphasis of the Oxman and
      Guyatt scores on the appraisal of bias in selection and validity assessment
      (inadequate in five reviews). CONCLUSIONS: Multiple systematic reviews on the
      same clinical topic varied in quality of reporting and recommendations. Longer
      manuscripts and previous not for profit funding were associated with higher
      quality.

PMID- 16415337
TI  - The impact of hospital management reforms on absenteeism in Costa Rica.
AB  - The reduction of high levels of absenteeism among health care workers was one the
      objectives of the reforms undertaken to improve public hospital performance
      during the 1990s in Costa Rica. This paper attempts to assess the impact of
      changes in reimbursement methods and organizational reform on absence rates among
      health care personnel in Costa Rican public hospitals for the period 1995-2001.
      Our results show the reforms to have had a negative impact on absenteeism, which
      increased throughout the considered period. Results further indicate that the
      policy of not substituting absentee workers, which was introduced through the
      reforms, did not work as expected in a permissive environment in which peer
      pressure mechanisms were lacking. In addition, the explicit incentives for
      workers included in the reforms were retained and used at facility level. There
      is a pressing need in the future for control and disciplinary mechanisms for
      health care personnel and for the introduction of absence rates as an explicit
      goal to be monitored and evaluated.

PMID- 16415338
TI  - The prospects of creating 'fiscal space' for the health sector.

PMID- 16415339
TI  - Improving access to pharmaceuticals in Brazil and Argentina.
AB  - The population of many Latin American countries is having increasing difficulty
      in accessing needed medicines due to the rise in their unitary cost and the
      growing number of poor in most countries of the region. A number of countries
      have taken steps to increase access to pharmaceuticals and have had different
      levels of success. This article reports on two country-wide programmes: the AIDS
      programme in Brazil, which has been judged as being highly successful, and the
      Remediar programme that has been implemented recently in Argentina. Both
      programmes have significantly increased access to needed pharmaceuticals, and
      Argentina has done it in a record time. In the discussion, we suggest that
      pharmaceutical interventions are successful when there is a firm political
      commitment, they are comprehensive, include the participation of civil society,
      and use a combination of methods to control the rising cost of medicines,
      including centralized international competitive bidding processes for drug
      procurement and reliance on multi-source drugs.

PMID- 16415340
TI  - The DNA-binding domain of the yeast Spt10p activator includes a zinc finger that
      is homologous to foamy virus integrase.
AB  - The yeast SPT10 gene encodes a putative histone acetyltransferase that binds
      specifically to pairs of upstream activating sequence (UAS) elements found only
      in the histone gene promoters. Here, we demonstrate that the DNA-binding domain
      of Spt10p is located between residues 283 and 396 and includes a His(2)-Cys(2)
      zinc finger. The binding of Spt10p to the histone UAS is zinc-dependent and is
      disabled by a zinc finger mutation (C388S). The isolated DNA-binding domain binds
      to single histone UAS elements with high affinity. In contrast, full-length
      Spt10p binds with high affinity only to pairs of UAS elements with very strong
      positive cooperativity and is unable to bind to a single UAS element. This
      implies the presence of a "blocking" domain in full-length Spt10p, which forces
      it to search for a pair of UAS elements. Chromatin immunoprecipitation
      experiments indicate that, unlike wild-type Spt10p, the C388S protein does not
      bind to the promoter of the gene encoding histone H2A (HTA1) in vivo. The C388S
      mutant has a phenotype similar to that of the spt10Delta mutant: poor growth and
      global aberrations in gene expression. Thus, the C388S mutation disables the DNA
      binding function of Spt10p in vitro and in vivo. The zinc finger of Spt10p is
      homologous to that of foamy virus integrase, perhaps suggesting that this
      integrase is also a sequence-specific DNA-binding protein.

PMID- 16415341
TI  - PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with
      substrates.
AB  - Many ATP-dependent molecular chaperones, including Hsp70, Hsp90, and the
      chaperonins GroEL/Hsp60, require cofactor proteins to regulate their ATPase
      activities and thus folding functions in vivo. One conspicuous exception has been
      the eukaryotic chaperonin CCT, for which no regulator of its ATPase activity,
      other than non-native substrate proteins, is known. We identify the
      evolutionarily conserved PhLP3 (phosducin-like protein 3) as a modulator of CCT
      function in vitro and in vivo. PhLP3 binds CCT, spanning the cylindrical
      chaperonin cavity and contacting at least two subunits. When present in a ternary
      complex with CCT and an actin or tubulin substrate, PhLP3 significantly
      diminishes the chaperonin ATPase activity, and accordingly, excess PhLP3 perturbs
      actin or tubulin folding in vitro. Most interestingly, however, the Saccharomyces
      cerevisiae PhLP3 homologue is required for proper actin and tubulin function.
      This cellular role of PhLP3 is most apparent in a strain that also lacks
      prefoldin, a chaperone that facilitates CCT-mediated actin and tubulin folding.
      We propose that the antagonistic actions of PhLP3 and prefoldin serve to modulate
      CCT activity and play a key role in establishing a functional cytoskeleton in
      vivo.

PMID- 16415343
TI  - Ionic contacts at DnaK substrate binding domain involved in the allosteric
      regulation of lid dynamics.
AB  - To gain further insight into the interactions involved in the allosteric
      transition of DnaK we have characterized wild-type (wt) protein and three mutants
      in which ionic interactions at the interface between the two subdomains of the
      substrate binding domain, and within the lid subdomain have been disrupted. Our
      data show that ionic contacts, most likely forming an electrically charged
      network, between the N-terminal region of helix B and an inner loop of the beta
      sandwich are involved in maintaining the position of the lid relative to the beta
      subdomain in the ADP state but not in the ATP state of the protein. Disruption of
      the ionic interactions between the C-terminal region of helix B and the outer
      loops of the beta-sandwich, known as the latch, does not have the same
      conformational consequences but results equally in an inactive protein. This
      indicates that a variety of mechanisms can inactivate this complex allosteric
      machine. Our results identify the ionic contacts at the subdomain and interdomain
      interfaces that are part of the hinge region involved in the ATP-induced
      allosteric displacement of the lid away from the peptide binding site. These
      interactions also stabilize peptide-Hsp70 complexes at physiological (37 degrees
      C) and stress (42 degrees C) temperatures, a requirement for productive substrate
      (re)folding.

PMID- 16415344
TI  - Expression profiling of a hypercontraction-induced myopathy in Drosophila
      suggests a compensatory cytoskeletal remodeling response.
AB  - Mutations that alter muscle contraction lead to a large array of diseases,
      including muscular dystrophies and cardiomyopathies. Although the molecular
      lesions underlying many hereditary muscle diseases are known, the downstream
      pathways that contribute to disease pathogenesis and compensatory muscle
      remodeling are poorly defined. We have recently identified and characterized
      mutations in Myosin Heavy Chain (Mhc) that lead to hypercontraction and
      subsequent degeneration of flight muscles in Drosophila. To characterize the
      genomic response to hypercontraction-induced myopathy, we performed expression
      analysis using Affymetrix high density oligonucleotide microarrays in Drosophila
      Mhc hypercontraction alleles. The altered transcriptional profile of dystrophic
      Mhc muscles suggests an actin-dependent remodeling of the muscle cytoskeleton.
      Specifically, a subset of the highly up-regulated transcripts is involved in
      actin regulation and structural support for the contractile machinery. In
      addition, we identified previously uncharacterized proteins with putative actin
      interaction domains that are up-regulated in Mhc mutants and differentially
      expressed in muscles. Several of the up-regulated proteins, including the
      dystrophin-related protein, MSP-300, and the homolog of the neuronal activity
      regulated protein, ARC, localize to specific subcellular muscle structures that
      may provide key structural sites for cytoskeletal remodeling in dystrophic
      muscles. Defining the genome-wide transcriptional response to muscle
      hypercontraction in Drosophila has revealed candidate loci that may participate
      in the pathogenesis of muscular dystrophy and in compensatory muscle repair
      pathways through modulation of the actin cytoskeleton.

PMID- 16415342
TI  - Requirement of the protein B23 for nucleolar disassembly induced by the FRGY2a
      family proteins.
AB  - In Xenopus somatic cell nuclear cloning, the nucleoli of donor nuclei rapidly and
      almost completely disappear in egg cytoplasm. We previously showed that the germ
      cell-specific proteins FRGY2a and FRGY2b were responsible for this unusually
      drastic nucleolar disassembly. The nucleolar disassembly occurs without
      inhibition of pre-rRNA transcription, a well known trigger for nucleolar
      segregation, and the mechanism for the nucleolar disassembly by FRGY2a and FRGY2b
      remains largely unknown. In this study, we searched for FRGY2a-interacting
      proteins and investigated the functional consequences of their interactions
      through a series of experiments. We showed that during the nucleolar disassembly,
      FRGY2a localized to the nucleoli of isolated nuclei and was capable of
      disassembling purified nucleoli, suggesting a direct interaction between FRGY2a
      and nucleolar components. Using a His tag pulldown approach, we identified the
      abundant and multifunctional nucleolar protein B23 as a potential target of
      FRGY2a and its related human protein YB1. A specific interaction between
      FRGY2a/YB1 and B23 was confirmed by co-immunoprecipitation. Finally, B23
      knockdown using short interfering RNA and a subsequent add-back experiment
      confirmed that B23 was necessary for nucleolar disassembly by YB1. We propose
      that FRGY2a and YB1 disassemble nucleoli by sequestering B23, which is associated
      with pre-ribosomes and other structurally important nucleolar components.

PMID- 16415345
TI  - Contact inhibition of hepatocyte growth regulated by functional association of
      the c-Met/hepatocyte growth factor receptor and LAR protein-tyrosine phosphatase.
AB  - Contact inhibition, the inhibition of cell proliferation by tight cell-cell
      contact is a fundamental characteristic of normal cells. Using primary cultured
      hepatocytes, we investigated the mechanisms of contact inhibition that decrease
      the mitogenic activity of hepatocyte growth factor (HGF), focusing on the
      regulation of c-Met/HGF-receptor activation. In hepatocytes cultured at a sparse
      cell density, HGF stimulation induced prolonged c-Met tyrosine phosphorylation
      for over 5 h and a marked mitogenic response. In contrast, HGF stimulation
      induced transient c-Met tyrosine phosphorylation in <3 h and failed to induce
      mitogenic response in hepatocytes cultured at a confluent cell density. Treatment
      of the confluent cells with HGF plus orthovanadate, a broad spectrum protein
      tyrosine phosphatase inhibitor, however, prolonged c-Met tyrosine phosphorylation
      for over 5 h and permitted the subsequent mitogenic response. The mitogenic
      response to HGF was associated with the duration of c-Met tyrosine
      phosphorylation even in the sparse cells. We found that the activity and
      expression of the protein-tyrosine phosphatase LAR increased following HGF
      stimulation specifically in confluent hepatocytes and not in sparse hepatocytes.
      LAR and c-Met were associated, and purified LAR dephosphorylated tyrosine
      phosphorylated c-Met in in vitro phosphatase reactions. Furthermore, antisense
      oligonucleotides specific for LAR mRNA suppressed the expression of LAR, allowed
      prolonged c-Met tyrosine phosphorylation, and led to acquisition of a mitogenic
      response in hepatocytes even under the confluent condition. Thus functional
      association of LAR and c-Met underlies the inhibition of c-Met-mediated mitogenic
      signaling through the dephosphorylation of c-Met, which specifically occurs under
      the confluent condition.

PMID- 16415346
TI  - Drosophila myosin VIIA is a high duty ratio motor with a unique kinetic
      mechanism.
AB  - Mutations of myosin VIIA cause deafness in various species from human and mice to
      Zebrafish and Drosophila. We analyzed the kinetic mechanism of the ATPase cycle
      of Drosophila myosin VIIA by using a single-headed construct with the entire neck
      domain. The steady-state ATPase activity (0.06 s(-1)) was markedly activated by
      actin to yield V(max) and K(ATPase) of 1.72 s(-1) and 3.2 microm, respectively.
      The most intriguing finding is that the ATP hydrolysis predominantly takes place
      in the actin-bound form (actin-attached hydrolysis) for the actomyosin VIIA
      ATPase reaction. The ATP hydrolysis rate was much faster for the actin-attached
      form than the dissociated form, in contrast to other myosins reported so far.
      Both the ATP hydrolysis step and the phosphate release step were significantly
      faster than the entire ATPase cycle rate, thus not rate-determining. The rate of
      ADP dissociation from actomyosin VIIA was 1.86 s(-1), which was comparable with
      the overall ATPase cycle rate, thus assigned to be a rate-determining step. The
      results suggest that Drosophila myosin VIIA spends the majority of the ATPase
      cycle in an actomyosin.ADP form, a strong actin binding state. The duty ratio
      calculated from our kinetic model was approximately 0.9. Therefore, myosin VIIA
      is classified to be a high duty ratio motor. The present results suggested that
      myosin VIIA can be a processive motor to serve cargo trafficking in cells once it
      forms a dimer structure.

PMID- 16415347
TI  - Unusual structural features of the bacteriophage-associated hyaluronate lyase
      (hylp2).
AB  - Hyaluronate lyases are a class of endoglycosaminidase enzymes, which are of
      considerable complexity and heterogeneity. Their primary function is to degrade
      hyaluronan and certain other glycosaminoglycans and facilitate the spread of
      disease. Among hyaluronate lyases, the bacteriophage-associated enzymes are
      unique as they have the lowest molecular mass, very low amino acid sequence
      homology with bacterial hyaluronate lyases, and exhibit absolute specificity for
      one type of glycosaminoglycan, i.e. hyaluronan. Despite such unique
      characteristics significant details on structural features of these lyases are
      not available. The Streptococcus pyogenes bacteriophage 10403 contains a gene,
      hylP2, which encodes for hyaluronate lyase (HylP2) in this organism. HylP2 was
      cloned, overexpressed, and purified to homogeneity. The recombinant HylP2 exists
      as a homotrimer of molecular mass about 110 kDa, under physiological conditions.
      Limited proteolysis and guanidine hydrochloride denaturation studies demonstrated
      that the N-terminal region of the protein is flexible, whereas the C-terminal
      portion has a compact conformation. The enzyme shows sequential unfolding, with
      the N-terminal unfolding first followed by the simultaneous unfolding and
      dissociation of the stabilized trimeric C-terminal domain. We isolated a
      functionally active C-terminal fragment (Ser(128)-Lys(337)) of the protein that
      was stabilized in a trimeric configuration. Comparative functional studies with
      full-length protein, N:C complex, and isolated C-terminal domain demonstrated
      that the active site of HylP2 is present in the C-terminal portion of the enzyme,
      and the N-terminal portion modulates the substrate specificity and enzymatic
      activity of the C-terminal domain.

PMID- 16415348
TI  - Protein kinase-mediated regulation of calcineurin through the phosphorylation of
      modulatory calcineurin-interacting protein 1.
AB  - Calcineurin is a serine/threonine protein phosphatase that plays a critical role
      in many physiologic processes such as T-cell activation, skeletal myocyte
      differentiation, and cardiac hypertrophy. We previously showed that active MEKK3
      is capable of stimulating calcineurin/nuclear factor of activated T-cells (NFAT)
      signaling in cardiac myocytes through phosphorylation of modulatory calcineurin
      interacting protein 1 (MCIP1). However, the protein kinases that function
      downstream of MEKK3 to mediate MCIP1 phosphorylation and the mechanism of MCIP1
      mediated calcineurin regulation have not been defined. Here, we show that MEK5
      and big MAP kinase 1 (BMK1) function downstream of MEKK3 in a signaling cascade
      that induces calcineurin activity through phosphorylation of MCIP1. Genetic
      studies showed that BMK1-deficient mouse lung fibroblasts failed to mediate MCIP1
      phosphorylation and activate calcineurin/NFAT in response to angiotensin II, a
      potent NFAT activator. Conversely, restoring BMK1 to the deficient cells restored
      angiotensin II-mediated calcineurin/NFAT activation. Thus, using BMK1-deficient
      mouse lung fibroblast cells, we provided the genetic evidence that BMK1 is
      required for angiotensin II-mediated calcineurin/NFAT activation through MICP1
      phosphorylation. Finally, we discovered that phosphorylated MCIP1 dissociates
      from calcineurin and binds with 14-3-3, thereby relieving its inhibitory effect
      on calcineurin activity. In summary, our findings reveal a previously
      unrecognized essential regulatory role of mitogen-activated protein kinase
      signaling in calcineurin activation through the reversible phosphorylation of a
      calcineurin-interacting protein, MCIP1.

PMID- 16415349
TI  - Candida albicans Spt23p controls the expression of the Ole1p Delta9 fatty acid
      desaturase and regulates unsaturated fatty acid biosynthesis.
AB  - In Saccharomyces cerevisiae the endoplasmic reticulum membrane proteins scSpt23p
      and scMga2p control the formation of unsaturated fatty acids by a mechanism that
      involves their release from the membrane by ubiquitin-mediated proteolysis. The
      resulting soluble polypeptides act as transcription activators that specifically
      control the expression of scOLE1, a gene that encodes scOle1p, a Delta9 fatty
      acid desaturase that forms cis-monounsaturated fatty acids (9Z-16:1 and 9Z-18:1)
      from saturated fatty acyl-CoA precursors. ScOle1p is the only long chain fatty
      acid desaturase in Saccharomyces and its membrane and storage lipids contain only
      saturated fatty acids and the monounsaturated products of that enzyme. Most other
      fungi, however, express multiple endoplasmic reticulum desaturases, including
      enzymes that form both mono- and polyunsaturated fatty acids. These typically
      include Delta12 and Delta15 enzymes that form the polyunsaturated species, 9Z,12Z
      18:2, and 9Z,12Z,15Z-18:3, which are the most abundant fatty acids in membrane
      and storage lipids. An analysis of genomic DNA sequences shows that Candida
      albicans has a single homologue of the Saccharomyces scSPT23 and scMGA2 genes
      that we designate here as caSPT23. This study describes the characterization of
      the caSPT23 gene product and shows that it can repair the unsaturated fatty acid
      auxotrophy when it is expressed in a Saccharomyces scspt23Delta;scmga2Delta
      strain. In addition we show caSPT23 is essential for the expression of one of the
      two Delta9 desaturase homologues in Candida and potentially other functions
      associated with fatty acid metabolism.

PMID- 16415350
TI  - Formation, structure, and dissociation of the ribonuclease S three-dimensional
      domain-swapped dimer.
AB  - Post-translational events, such as proteolysis, are believed to play essential
      roles in amyloid formation in vivo. Ribonuclease A forms oligomers by the three
      dimensional domain-swapping mechanism. Here, we demonstrate the ability of
      ribonuclease S, a proteolytically cleaved form of ribonuclease A, to oligomerize
      efficiently. This unexpected capacity has been investigated to study the effect
      of proteolysis on oligomerization and amyloid formation. The yield of the RNase S
      dimer was found to be significantly higher than that of RNase A dimers, which
      suggests that proteolysis can activate oligomerization via the three-dimensional
      domain-swapping mechanism. Characterization by chromatography, enzymatic assays,
      and NMR spectroscopy indicate that the structure of the RNase S dimer is similar
      to that of the RNase A C-dimer. The RNase S dimer dissociates much more readily
      than the RNase A C-dimer does. By measuring the dissociation rate as a function
      of temperature, the activation enthalpy and entropy for RNase S dimer
      dissociation were found to resemble those for the release of the small fragment
      (S-peptide) from monomeric RNase S. Excess S-peptide strongly slows RNase S dimer
      dissociation. These results strongly suggest that S-peptide release is the rate
      limiting step of RNase S dimer dissociation.

PMID- 16415351
TI  - The cytotoxic lymphocyte protease, granzyme B, targets the cytoskeleton and
      perturbs microtubule polymerization dynamics.
AB  - Granzyme B, a serine protease derived from cytotoxic T lymphocyte (CTL) and
      Natural Killer (NK) cell granules, plays an important role in coordinating
      apoptosis of CTL and NK target cells. Here, we report that granzyme B targets the
      cytoskeleton by cleaving and removing the acidic C-terminal tail of alpha
      tubulin. Consistent with this, Granzyme B markedly enhanced rates of microtubule
      polymerization in vitro, most likely by removal of an autoinhibitory domain
      within the tubulin C terminus. Moreover, delivery of Granzyme B into HeLa target
      cells promoted dramatic reorganization of the microtubule network in a caspase
      independent manner. These data reveal that granzyme B directly attacks a major
      component of the cell cytoskeleton, which may contribute to the incapacitation of
      target cells during CTL/NK-mediated killing.

PMID- 16415352
TI  - Identification and characterization of an 8-kDa light chain associated with
      Dictyostelium discoideum MyoB, a class I myosin.
AB  - Dictyostelium discoideum MyoB is a single-headed class I myosin. Analysis of
      purified MyoB by SDS-PAGE indicated the presence of an approximately 9-kDa light
      chain. A tryptic digest of MyoB yielded a partial sequence for the light chain
      that exactly matched a sequence in a 73-amino acid, 8,296-Da protein (dictyBase
      number DDB0188713). This protein, termed MlcB, contains two EF-hand motifs and
      shares approximately 30% sequence identity with the N- and C-terminal lobes of
      calmodulin. FLAG-MlcB expressed in Dictyostelium co-immunoprecipitated with MyoB
      but not with the related class myosins and MyoD. Recombinant MlcB bound Ca2+ with
      a Kd value of 0.2 microm and underwent a Ca2+-induced change in conformation that
      increased alpha-helical content and surface hydrophobicity. Mutational analysis
      showed that the first EF-hand was responsible for Ca2+ binding. In the presence
      and absence of Ca2+ MlcB was a monomer in solution and bound to a MyoB IQ motif
      peptide with a Kd value of approximately 0.5 microm. A MyoB head-neck construct
      with a Ser to Glu mutation at the TEDS site bound MlcB and displayed an actin
      activated Mg2+ ATPase activity that was insensitive to Ca2+. We conclude that
      MlcB represents a novel type of small myosin light chain that binds to IQ motifs
      in a manner comparable with a single lobe of a typical four-EF-hand protein.

PMID- 16415353
TI  - Hsp70 chaperone machine remodels protein aggregates at the initial step of Hsp70
      Hsp100-dependent disaggregation.
AB  - Exposure to temperatures over a certain limit leads to massive protein
      aggregation in the cell. Disaggregation of such aggregates is largely dependent
      on the Hsp100 and Hsp70 chaperones. The exact role of the Hsp70 chaperone machine
      (composed of DnaK, DnaJ, and GrpE) in the Hsp100-dependent process remains
      unknown. In this study we focused on the Hsp70 role at the initial step of the
      disaggregation process. Two different aggregated model substrates, green
      fluorescent protein (GFP) and firefly luciferase, were incubated with the Hsp70
      machine resulting in efficient fragmentation of large aggregates into smaller
      ones. Our data suggest that the observed fragmentation is achieved first by
      extraction of polypeptides from aggregates in Hsp70 chaperone machine-dependent
      manner and not by direct fragmentation of large aggregates. In the absence of
      Hsp100 (ClpB) these "extracted" polypeptides were not able to fold properly and
      promptly reassociated into new aggregates. The extracted GFP molecules were
      efficiently recognized and sequestered by a molecular trap, the mutant GroEL
      D87K, which binds stably to unfolded but not to native polypeptides. The binding
      of extracted GFP molecules to the GroEL trap prevented their reaggregation. We
      propose that the Hsp70 machine disentangles polypeptides from protein aggregates
      prior to Hsp100 action.

PMID- 16415354
TI  - Functional and trafficking defects in ATP binding cassette A3 mutants associated
      with respiratory distress syndrome.
AB  - Members of the ATP binding cassette (ABC) protein superfamily actively transport
      a wide range of substrates across cell and intracellular membranes. Mutations in
      ABCA3, a member of the ABCA subfamily with unknown function, lead to fatal
      respiratory distress syndrome (RDS) in the newborn. Using cultured human lung
      cells, we found that recombinant wild-type hABCA3 localized to membranes of both
      lysosomes and lamellar bodies, which are the intracellular storage organelles for
      surfactant. In contrast, hABCA3 with mutations linked to RDS failed to target to
      lysosomes and remained in the endoplasmic reticulum as unprocessed forms.
      Treatment of those cells with the chemical chaperone sodium 4-phenylbutyrate
      could partially restore trafficking of mutant ABCA3 to lamellar body-like
      structures. Expression of recombinant ABCA3 in non-lung human embryonic kidney
      293 cells induced formation of lamellar body-like vesicles that contained lipids.
      Small interfering RNA knockdown of endogenous hABCA3 in differentiating human
      fetal lung alveolar type II cells resulted in abnormal, lamellar bodies
      comparable with those observed in vivo with mutant ABCA3. Silencing of ABCA3
      expression also reduced vesicular uptake of surfactant lipids
      phosphatidylcholine, sphingomyelin, and cholesterol but not
      phosphatidylethanolamine. We conclude that ABCA3 is required for lysosomal
      loading of phosphatidylcholine and conversion of lysosomes to lamellar body-like
      structures.

PMID- 16415355
TI  - Regulation of autophagy by sphingosine kinase 1 and its role in cell survival
      during nutrient starvation.
AB  - The sphingolipid ceramide induces macroautophagy (here called autophagy) and cell
      death with autophagic features in cancer cells. Here we show that overexpression
      of sphingosine kinase 1 (SK1), an enzyme responsible for the production of
      sphingosine 1-phosphate (S1P), in MCF-7 cells stimulates autophagy by increasing
      the formation of LC3-positive autophagosomes and the rate of proteolysis
      sensitive to the autophagy inhibitor 3-methyladenine. Autophagy was blocked in
      the presence of dimethylsphingosine, an inhibitor of SK activity, and in cells
      expressing a catalytically inactive form of SK1. In SK1(wt)-overexpressing cells,
      however, autophagy was not sensitive to fumonisin B1, an inhibitor of ceramide
      synthase. In contrast to ceramide-induced autophagy, SK1(S1P)-induced autophagy
      is characterized by (i) the inhibition of mammalian target of rapamycin signaling
      independently of the Akt/protein kinase B signaling arm and (ii) the lack of
      robust accumulation of the autophagy protein Beclin 1. In addition, nutrient
      starvation induced both the stimulation of autophagy and SK activity. Knocking
      down the expression of the autophagy protein Atg7 or that of SK1 by siRNA
      abolished starvation-induced autophagy and increased cell death with apoptotic
      hallmarks. In conclusion, these results show that SK1(S1P)-induced autophagy
      protects cells from death with apoptotic features during nutrient starvation.

PMID- 16415356
TI  - Hos2 and Set3 promote integration of Ty1 retrotransposons at tRNA genes in
      Saccharomyces cerevisiae.
AB  - The yeast LTR retrotransposon Ty1 integrates preferentially into regions upstream
      of tRNA genes. The chromatin structure of transcriptionally active tRNA genes is
      known to be important for Ty1 integration, but specific chromatin factors that
      enhance integration at tRNA genes have not been identified. Here we report that
      the histone deacetylase, Hos2, and the Trithorax-group protein, Set3, both
      components of the Set3 complex (Set3C), enhance transposition of chromosomal Ty1
      elements by promoting integration into the upstream region of tRNA genes.
      Deletion of HOS2 or SET3 reduced the mobility of a chromosomal Ty1his3AI element
      about sevenfold. Despite the fact that Ty1his3AI RNA, total Ty1 RNA, and total
      Ty1 cDNA levels were not reduced in hos2delta or set3delta mutants, transposition
      of endogenous Ty1 elements into the upstream regions of tRNA(Gly) genes was
      substantially decreased. Furthermore, when equivalent numbers of Ty1HIS3 mobility
      events launched from a pGAL1:Ty1his3AI plasmid were analyzed, only one-quarter to
      one-half as many were found upstream of tRNA(Gly) genes in a hos2delta or
      set3delta mutant than in a wild-type strain. Chromatin immunoprecipitation
      analysis revealed that Hos2 is physically associated with tRNA genes. Taken
      together, our results support the hypothesis that Hos2 and Set3 function at tRNA
      genes to promote Ty1 integration.

PMID- 16415357
TI  - A simple genetic incompatibility causes hybrid male sterility in mimulus.
AB  - Much evidence has shown that postzygotic reproductive isolation (hybrid
      inviability or sterility) evolves by the accumulation of interlocus
      incompatibilities between diverging populations. Although in theory only a single
      pair of incompatible loci is needed to isolate species, empirical work in
      Drosophila has revealed that hybrid fertility problems often are highly polygenic
      and complex. In this article we investigate the genetic basis of hybrid sterility
      between two closely related species of monkeyflower, Mimulus guttatus and M.
      nasutus. In striking contrast to Drosophila systems, we demonstrate that nearly
      complete hybrid male sterility in Mimulus results from a simple genetic
      incompatibility between a single pair of heterospecific loci. We have genetically
      mapped this sterility effect: the M. guttatus allele at the hybrid male sterility
      1 (hms1) locus acts dominantly in combination with recessive M. nasutus alleles
      at the hybrid male sterility 2 (hms2) locus to cause nearly complete hybrid male
      sterility. In a preliminary screen to find additional small-effect male sterility
      factors, we identified one additional locus that also contributes to some of the
      variation in hybrid male fertility. Interestingly, hms1 and hms2 also cause a
      significant reduction in hybrid female fertility, suggesting that sex-specific
      hybrid defects might share a common genetic basis. This possibility is supported
      by our discovery that recombination is reduced dramatically in a cross involving
      a parent with the hms1-hms2 incompatibility.

PMID- 16415358
TI  - Detecting adaptive trait introgression between Iris fulva and I. brevicaulis in
      highly selective field conditions.
AB  - The idea that natural hybridization has served as an important force in
      evolutionary and adaptive diversification has gained considerable momentum in
      recent years. By combining genome analyses with a highly selective field
      experiment, we provide evidence for adaptive trait introgression between two
      naturally hybridizing Louisiana Iris species, flood-tolerant Iris fulva and dry
      adapted I. brevicaulis. We planted reciprocal backcross (BC1) hybrids along with
      pure-species plants into natural settings that, due to a flooding event, favored
      I. fulva. As expected, I. fulva plants survived at much higher rates than I.
      brevicaulis plants. Backcross hybrids toward I. fulva (BCIF) also survived at
      significantly higher rates than the reciprocal backcross toward I. brevicaulis
      (BCIB). Survivorship of BCIB hybrids was strongly influenced by the presence of a
      number of introgressed I. fulva alleles located throughout the genome, while
      survivorship in the reciprocal BCIF hybrids was heavily influenced by two
      epistatically acting QTL of opposite effects. These results demonstrate the
      potential for adaptive trait introgression between these two species and may help
      to explain patterns of genetic variation observed in naturally occurring hybrid
      zones.

PMID- 16415359
TI  - Origin and evolution of processed pseudogenes that stabilize functional Makorin1
      mRNAs in mice, primates and other mammals.
AB  - We investigate the origin and evolution of a mouse processed pseudogene, Makorin1
      p1, whose transcripts stabilize functional Makorin1 mRNAs. It is shown that
      Makorin1-p1 originated almost immediately before the musculus and cervicolor
      species groups diverged from each other some 4 million years ago and that the
      Makorin1-p1 orthologs in various Mus species are transcribed. However, Mus caroli
      in the cervicolor species group expresses not only Makorin1-p1, but also another
      older Makorin1-derived processed pseudogene, demonstrating the rapid generation
      and turnover in subgenus Mus. Under this circumstance, transcribed processed
      pseudogenes (TPPs) of Makorin1 evolved in a strictly neutral fashion even with an
      enhanced substitution rate at CpG dinucleotide sites. Next, we extend our
      analyses to rats and other mammals. It is shown that although these species also
      possess their own Makorin1-derived TPPs, they occur rather infrequently in simian
      primates. Under this circumstance, it is hypothesized that already existing TPPs
      must be prevented from accumulating detrimental mutations by negative selection.
      This hypothesis is substantiated by the presence of two rather old TPPs, MKRNP1
      and MKRN4, in humans and New World monkeys. The evolutionary rate and pattern of
      Makorin1-derived processed pseudogenes depend heavily on how frequently they are
      disseminated in the genome.

PMID- 16415360
TI  - Concerted evolution of two novel protein families in Caenorhabditis species.
AB  - Among a large number of homologous gene clusters in C. elegans, two gene families
      that appear to undergo concerted evolution were studied in detail. Both gene
      families are nematode specific and encode small secreted proteins of unknown
      function. For both families in three Caenorhabditis species, concerted groups of
      genes are characterized by close genomic proximity and by genes in inverted
      orientation. The rate of protein evolution in one of the two families could be
      calibrated by comparison with a closely related nonconcerted singleton gene with
      one-to-one orthologs in all three species. This comparison suggests that protein
      evolution in concerted gene clusters is two- to sevenfold accelerated. A broader
      survey of clustered gene families, focused on adjacent inverted gene pairs,
      identified an additional seven families in which concerted evolution probably
      occurs. All nine identified families encode relatively small proteins, eight of
      them encode putative secreted proteins, and most of these have very unusual amino
      acid composition or sequence. I speculate that these genes encode rapidly
      evolving antimicrobial peptides.

PMID- 16415361
TI  - Regulation of hyphal morphogenesis and the DNA damage response by the Aspergillus
      nidulans ATM homolog AtmA.
AB  - Ataxia telangiectasia (A-T) is an inherited disorder characterized by progressive
      loss of motor function and susceptibility to cancer. The most prominent clinical
      feature observed in A-T patients is the degeneration of Purkinje motor neurons.
      Numerous studies have emphasized the role of the affected gene product, ATM, in
      the regulation of the DNA damage response. However, in Purkinje cells, the bulk
      of ATM localizes to the cytoplasm and may play a role in vesicle trafficking. The
      nature of this function, and its involvement in the pathology underlying A-T,
      remain unknown. Here we characterize the homolog of ATM (AtmA) in the filamentous
      fungus Aspergillus nidulans. In addition to its expected role in the DNA damage
      response, we find that AtmA is also required for polarized hyphal growth. We
      demonstrate that an atmA mutant fails to generate a stable axis of hyphal
      polarity. Notably, cytoplasmic microtubules display aberrant cortical
      interactions at the hyphal tip. Our results suggest that AtmA regulates the
      function and/or localization of landmark proteins required for the formation of a
      polarity axis. We propose that a similar function may contribute to the
      establishment of neuronal polarity.

PMID- 16415362
TI  - Gene expression from random libraries of yeast promoters.
AB  - Genomewide techniques to assay gene expression and transcription factor binding
      are in widespread use, but are far from providing predictive rules for the
      function of regulatory DNA. To investigate more intensively the grammar rules for
      active regulatory sequence, we made libraries from random ligations of a very
      restricted set of sequences. Working with the yeast Saccharomyces cerevisiae, we
      developed a novel screen based on the sensitivity of ascospores lacking
      dityrosine to treatment with lytic enzymes. We tested two separate libraries
      built by random ligation of a single type of activator site either for a well
      characterized sporulation factor, Ndt80, or for a new sporulation-specific
      regulatory site that we identified and several neutral spacer elements. This
      selective system achieved up to 1:10(4) enrichment of the artificial sequences
      that were active during sporulation, allowing a high-throughput analysis of large
      libraries of synthetic promoters. This is not practical with methods involving
      direct screening for expression, such as those based on fluorescent reporters.
      There were very few false positives, since active promoters always passed the
      screen when retested. The survival rate of our libraries containing roughly equal
      numbers of spacers and activators was a few percent that of libraries made from
      activators alone. The sequences of approximately 100 examples of active and
      inactive promoters could not be distinguished by simple binary rules; instead,
      the best model for the data was a linear regression fit of a quantitative measure
      of gene activity to multiple features of the regulatory sequence.

PMID- 16415363
TI  - Constructing genetic linkage maps under a tetrasomic model.
AB  - An international consortium has launched the whole-genome sequencing of potato,
      the fourth most important food crop in the world. Construction of genetic linkage
      maps is an inevitable step for taking advantage of the genome projects for the
      development of novel cultivars in the autotetraploid crop species. However,
      linkage analysis in autopolyploids, the kernel of linkage map construction, is
      theoretically challenging and methodologically unavailable in the current
      literature. We present here a theoretical analysis and a statistical method for
      tetrasomic linkage analysis with dominant and/or codominant molecular markers.
      The analysis reveals some essential properties of the tetrasomic model. The
      method accounts properly for double reduction and incomplete information of
      marker phenotype in regard to the corresponding phenotype in estimating the
      coefficients of double reduction and recombination frequency and in testing their
      significance by using the marker phenotype data. Computer simulation was
      developed to validate the analysis and the method and a case study with 201 AFLP
      and SSR markers scored on 228 full-sib individuals of autotetraploid potato is
      used to illustrate the utility of the method in map construction in
      autotetraploid species.

PMID- 16415364
TI  - Genetically engineered underdominance for manipulation of pest populations: a
      deterministic model.
AB  - We theoretically investigate the potential for introgressing a desired engineered
      gene into a pest population by linking the desired gene to DNA constructs that
      exhibit underdominance properties. Our deterministic model includes two
      independently segregating engineered constructs that both carry a lethal gene,
      but suppress each other. Only genotypes containing both or neither construct are
      viable. Both constructs also carry the desired gene with an independent
      regulatory mechanism. We examine the minimal number of individuals of an
      engineered strain that must be released into a natural population to successfully
      introgress the desired gene. We compare results for strains carrying single and
      multiple insertions of the constructs. When there are no fitness costs associated
      with the inserted constructs (when the lethal sequences are not expressed), the
      number of individuals that must be released decreases as the number of insertions
      in the genome of the released strain increases. As fitness costs increase, the
      number of individuals that must be released increases at a greater rate for
      release strains with more insertions. Under specific conditions this results in
      the strain with only a single insertion of each construct being the most
      efficient for introgressing the desired gene. We discuss practical implications
      of our findings.

PMID- 16415365
TI  - A novel forward genetic screen for identifying mutations affecting larval
      neuronal dendrite development in Drosophila melanogaster.
AB  - Vertebrate and invertebrate dendrites are information-processing compartments
      that can be found on both central and peripheral neurons. Elucidating the
      molecular underpinnings of information processing in the nervous system
      ultimately requires an understanding of the genetic pathways that regulate
      dendrite formation and maintenance. Despite the importance of dendrite
      development, few forward genetic approaches have been used to analyze the latest
      stages of dendrite development, including the formation of F-actin-rich dendritic
      filopodia or dendritic spines. We developed a forward genetic screen utilizing
      transgenic Drosophila second instar larvae expressing an actin, green fluorescent
      protein (GFP) fusion protein (actin::GFP) in subsets of sensory neurons.
      Utilizing this fluorescent transgenic reporter, we conducted a forward genetic
      screen of >4000 mutagenized chromosomes bearing lethal mutations that affected
      multiple aspects of larval dendrite development. We isolated 13 mutations on the
      X and second chromosomes composing 11 complementation groups affecting dendrite
      outgrowth/branching, dendritic filopodia formation, or actin::GFP localization
      within dendrites in vivo. In a fortuitous observation, we observed that the
      structure of dendritic arborization (da) neuron dendritic filopodia changes in
      response to a changing environment.

PMID- 16415366
TI  - A role for the septation initiation network in septum assembly revealed by
      genetic analysis of sid2-250 suppressors.
AB  - In the fission yeast Schizosaccharomyces pombe the septation initiation network
      (SIN) is required for stabilization of the actomyosin ring in late mitosis as
      well as for ring constriction and septum deposition. In a genetic screen for
      suppressors of the SIN mutant sid2-250, we isolated a mutation, ace2-35, in the
      transcription factor Ace2p. Both ace2Delta and ace2-35 show defects in cell
      separation, and both can rescue the growth defects of some SIN mutants at low
      restrictive temperatures, where the SIN single mutants lyse at the time of
      cytokinesis. By detailed analysis of the formation and constriction of the
      actomyosin ring and septum in the sid2-250 mutant at low restrictive
      temperatures, we show that the lysis phenotype of the sid2-250 mutant is likely
      due to a weak cell wall and septum combined with enzymatic activity of septum
      degrading enzymes. Consistent with the recent findings that Ace2p controls
      transcription of genes involved in cell separation, we show that disruption of
      some of these genes can also rescue sid2-250 mutants. Consistent with SIN mutants
      having defects in septum formation, many SIN mutants can be rescued at the low
      restrictive temperature by the osmotic stabilizer sorbitol. The small GTPase Rho1
      is known to promote cell wall formation, and we find that Rho1p expressed from a
      multi-copy plasmid can also rescue sid2-250 at the low restrictive temperature.
      Together these results suggest that the SIN has a role in promoting proper cell
      wall formation at the division septa.

PMID- 16415367
TI  - Suppressor analysis of a histone defect identifies a new function for the hda1
      complex in chromosome segregation.
AB  - Histones are essential for the compaction of DNA into chromatin and therefore
      participate in all chromosomal functions. Specific mutations in HTA1, one of the
      two Saccharomyces cerevisiae genes encoding histone H2A, have been previously
      shown to cause chromosome segregation defects, including an increase in ploidy
      associated with altered pericentromeric chromatin structure, suggesting a role
      for histone H2A in kinetochore function. To identify proteins that may interact
      with histone H2A in the control of ploidy and chromosome segregation, we
      performed a genetic screen for suppressors of the increase-in-ploidy phenotype
      associated with one of the H2A mutations. We identified five genes, HHT1, MKS1,
      HDA1, HDA2, and HDA3, four of which encode proteins directly connected to
      chromatin function: histone H3 and each of the three subunits of the Hda1 histone
      deacetylase complex. Our results show that Hda3 has functions distinct from Hda2
      and Hda1 and that it is required for normal chromosome segregation and cell cycle
      progression. In addition, HDA3 shows genetic interactions with kinetochore
      components, emphasizing a role in centromere function, and all three Hda proteins
      show association with centromeric DNA. These findings suggest that the Hda1
      deacetylase complex affects histone function at the centromere and that Hda3 has
      a distinctive participation in chromosome segregation. Moreover, these
      suppressors provide the basis for future studies regarding histone function in
      chromosome segregation.

PMID- 16415368
TI  - Mapping quantitative trait loci in noninbred mosquito crosses.
AB  - The identification of genes that affect quantitative traits has been of great
      interest to geneticists for many decades, and many statistical methods have been
      developed to map quantitative trait loci (QTL). Most QTL mapping studies in
      experimental organisms use purely inbred lines, where the two homologous
      chromosomes in each individual are identical. As a result, many existing QTL
      mapping methods developed for experimental organisms are applicable only to
      genetic crosses between inbred lines. However, it may be difficult to obtain
      inbred lines for certain organisms, e.g., mosquitoes. Although statistical
      methods for QTL mapping in outbred populations, e.g., humans, can be applied for
      such crosses, these methods may not fully take advantage of the uniqueness of
      these crosses. For example, we can generally assume that the two grandparental
      lines are homozygous at the QTL of interest, but such information is not be
      utilized through methods developed for outbred populations. In addition, mating
      types and phases can be relatively easy to establish through the analysis of
      adjacent markers due to the large number of offspring that can be collected,
      substantially simplifying the computational need. In this article, motivated by a
      mosquito intercross experiment involving two selected lines that are not
      genetically homozygous across the genome, we develop statistical methods for QTL
      mapping for genetic crosses involving noninbred lines. In our procedure, we first
      infer parental mating types and use likelihood-based methods to infer phases in
      each parent on the basis of genotypes of offspring and one parent. A hidden
      Markov model is then employed to estimate the number of high-risk alleles at
      marker positions and putative QTL positions between markers in each offspring,
      and QTL mapping is finally conducted through the inferred QTL configuration
      across all offspring in all crosses. The performance of the proposed methods is
      assessed through simulation studies, and the usefulness of this method is
      demonstrated through its application to a mosquito data set.

PMID- 16415369
TI  - Identification of guanylyl cyclases that function in thermosensory neurons of
      Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans senses temperature primarily via the AFD
      thermosensory neurons in the head. The response to temperature can be observed as
      a behavior called thermotaxis on thermal gradients. It has been shown that a
      cyclic nucleotide-gated ion channel (CNG channel) plays a critical role in
      thermosensation in AFD. To further identify the thermosensory mechanisms in AFD,
      we attempted to identify components that function upstream of the CNG channel by
      a reverse genetic approach. Genetic and behavioral analyses showed that three
      members of a subfamily of gcy genes (gcy-8, gcy-18, and gcy-23) encoding guanylyl
      cyclases were essential for thermotaxis in C. elegans. Promoters of each gene
      drove reporter gene expression exclusively in the AFD neurons and, moreover,
      tagged proteins were localized to the sensory endings of AFD. Single mutants of
      each gcy gene showed almost normal thermotaxis. However, animals carrying double
      and triple mutations in these genes showed defective thermotaxis behavior. The
      abnormal phenotype of the gcy triple mutants was rescued by expression of any one
      of the three GCY proteins in the AFD neurons. These results suggest that three
      guanylyl cyclases function redundantly in the AFD neurons to mediate
      thermosensation by C. elegans.

PMID- 16415370
TI  - Maize adaptation to temperate climate: relationship between population structure
      and polymorphism in the Dwarf8 gene.
AB  - To investigate the genetic basis of maize adaptation to temperate climate,
      collections of 375 inbred lines and 275 landraces, representative of American and
      European diversity, were evaluated for flowering time under short- and long-day
      conditions. The inbred line collection was genotyped for 55 genomewide simple
      sequence repeat (SSR) markers. Comparison of inbred line population structure
      with that of landraces, as determined with 24 SSR loci, underlined strong effects
      of both historical and modern selection on population structure and a clear
      relationship with geographical origins. The late tropical groups and the early
      "Northern Flint" group from the northern United States and northern Europe
      exhibited different flowering times. Both collections were genotyped for a 6-bp
      insertion/deletion in the Dwarf8 (D8idp) gene, previously reported to be
      potentially involved in flowering time variation in a 102 American inbred panel.
      Among-group D8idp differentiation was much higher than that for any SSR marker,
      suggesting diversifying selection. Correcting for population structure, D8idp was
      associated with flowering time under long-day conditions, the deletion allele
      showing an average earlier flowering of 29 degree days for inbreds and 145 degree
      days for landraces. Additionally, the deletion allele occurred at a high
      frequency (>80%) in Northern Flint while being almost absent (<5%) in tropical
      materials. Altogether, these results indicate that Dwarf8 could be involved in
      maize climatic adaptation through diversifying selection for flowering time.

PMID- 16415371
TI  - Snf1-dependent and Snf1-independent pathways of constitutive ADH2 expression in
      Saccharomyces cerevisiae.
AB  - The transcription factor Adr1 directly activates the expression of genes encoding
      enzymes in numerous pathways that are upregulated after the exhaustion of glucose
      in the yeast Saccharomyces cerevisiae. ADH2, encoding the alcohol dehydrogenase
      isozyme required for ethanol oxidation, is a highly glucose-repressed, Adr1
      dependent gene. Using a genetic screen we isolated >100 mutants in 12
      complementation groups that exhibit ADR1-dependent constitutive ADH2 expression
      on glucose. Temperature-sensitive alleles are present among the new constitutive
      mutants, indicating that essential genes play a role in ADH2 repression. Among
      the genes we cloned is MOT1, encoding a repressor that inhibits TBP binding to
      the promoter, thus linking glucose repression with TBP access to chromatin. Two
      genes encoding proteins involved in vacuolar function, FAB1 and VPS35, and CDC10,
      encoding a nonessential septin, were also uncovered in the search, suggesting
      that vacuolar function and the cytoskeleton have previously unknown roles in
      regulating gene expression. Constitutive activation of ADH2 expression by Adr1 is
      SNF1-dependent in a strain with a defective MOT1 gene, whereas deletion of SNF1
      did not affect constitutive ADH2 expression in the mutants affecting vacuolar or
      septin function. Thus, the mutant search revealed previously unknown Snf1
      dependent and -independent pathways of ADH2 expression.

PMID- 16415374
TI  - Adult hypertension and kidney disease: the role of fetal programming.
AB  - Hypertension (HTN) and chronic kidney disease are highly prevalent diseases that
      tend to occur more frequently among disadvantaged populations, in whom prenatal
      care also tends to be poor. More and more evidence is emerging highlighting the
      important role of fetal programming in the development of adult disease,
      suggesting a possible common pathophysiologic denominator in the development of
      these disorders. Epidemiologic evidence accumulated over the past 2 decades has
      demonstrated an association between low birth weight and subsequent adult HTN,
      diabetes, and cardiovascular disease. More recently, a similar association has
      been found with chronic kidney disease. Animal studies and indirect evidence from
      human studies support the hypothesis that low birth weight, as a marker of
      adverse intrauterine circumstances, is associated with a congenital deficit in
      nephron number. The precise mechanism of the reduction in nephron number has not
      been established, but several hypotheses have been put forward, including changes
      in DNA methylation, increased apoptosis in the developing kidney, alterations in
      renal renin-angiotensin system activity, and increased fetal glucocorticoid
      exposure. A reduction in nephron number is associated with compensatory
      glomerular hypertrophy and an increased susceptibility to renal disease
      progression. HTN in low birth weight individuals also appears to be mediated in
      part through a reduction in nephron number. Increased awareness of the
      implications of low birth weight and inadequate prenatal care should lead to
      public health policies that may have long-term benefits in curbing the epidemics
      of HTN, diabetes, and kidney disease in generations to come.

PMID- 16415373
TI  - Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows
      the progression of renal damage in salt-sensitive hypertension.
AB  - We hypothesized that the downregulation of Cyp2c by tumor necrosis factor (TNF)
      alpha contributes to hypertension and renal injury in salt-sensitive angiotensin
      hypertension. Male Sprague-Dawley rats were fed a high-salt diet (8% NaCl), and
      osmotic minipumps were implanted to deliver angiotensin II for 14 days. Rats were
      divided into 3 groups: high salt, angiotensin high salt, and angiotensin high
      salt administered the TNF-alpha blocker, etanercept. Arterial pressure increased
      from 94+/-5 to 148+/-7 mm Hg during week 1 in the angiotensin high-salt group,
      whereas etanercept slowed blood pressure elevation during the first week in the
      treated group (90+/-2 to 109+/-6 mm Hg). After 2 weeks, arterial pressure
      increased to 156+/-11 mm Hg in the angiotensin high-salt group and 141+/-6 mm Hg
      in the etanercept-treated group. Albuminuria and proteinuria were significantly
      elevated in angiotensin high-salt rats and were reduced in the etanercept-treated
      rats. Urinary monocyte chemoattractant protein-1 excretion significantly
      increased in the angiotensin high-salt group (275+/-47 versus 81+/-19 ng/day) and
      was decreased in the etanercept-treated group (153+/-31 ng/day). Angiotensin high
      salt rats also had a significant increase in renal monocyte/macrophage
      infiltration, and this was again attenuated by etanercept treatment. Renal
      expression of Cyp2c23 decreased, whereas renal epoxide hydrolase expression
      increased in angiotensin high-salt rats. Etanercept treatment increased Cyp2c23
      expression and lowered epoxide hydrolase expression. These data suggest that TNF
      alpha contributes to downregulation of Cyp2c23, blood pressure regulation, and
      renal injury in angiotensin high-salt hypertension.

PMID- 16415372
TI  - Presenilin-based genetic screens in Drosophila melanogaster identify novel notch
      pathway modifiers.
AB  - Presenilin is the enzymatic component of gamma-secretase, a multisubunit
      intramembrane protease that processes several transmembrane receptors, such as
      the amyloid precursor protein (APP). Mutations in human Presenilins lead to
      altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play
      an essential role in Notch receptor cleavage and signaling. The Notch pathway is
      a highly conserved signaling pathway that functions during the development of
      multicellular organisms, including vertebrates, Drosophila, and C. elegans.
      Recent studies have shown that Notch signaling is sensitive to perturbations in
      subcellular trafficking, although the specific mechanisms are largely unknown. To
      identify genes that regulate Notch pathway function, we have performed two
      genetic screens in Drosophila for modifiers of Presenilin-dependent Notch
      phenotypes. We describe here the cloning and identification of 19 modifiers,
      including nicastrin and several genes with previously undescribed involvement in
      Notch biology. The predicted functions of these newly identified genes are
      consistent with extracellular matrix and vesicular trafficking mechanisms in
      Presenilin and Notch pathway regulation and suggest a novel role for gamma
      tubulin in the pathway.

PMID- 16415375
TI  - Community lay rescuer automated external defibrillation programs: key state
      legislative components and implementation strategies: a summary of a decade of
      experience for healthcare providers, policymakers, legislators, employers, and
      community leaders from the American Heart Association Emergency Cardiovascular
      Care Committee, Council on Clinical Cardiology, and Office of State Advocacy.
AB  - Cardiovascular disease is a leading cause of death for adults > or =40 years of
      age. The American Heart Association (AHA) estimates that sudden cardiac arrest is
      responsible for about 250,000 out-of-hospital deaths annually in the United
      States. Since the early 1990s, the AHA has called for innovative approaches to
      reduce time to cardiopulmonary resuscitation (CPR) and defibrillation and improve
      survival from sudden cardiac arrest. In the mid-1990s, the AHA launched a public
      health initiative to promote early CPR and early use of automated external
      defibrillators (AEDs) by trained lay responders in community (lay rescuer) AED
      programs. Between 1995 and 2000, all 50 states passed laws and regulations
      concerning lay rescuer AED programs. In addition, the Cardiac Arrest Survival Act
      (CASA, Public Law 106-505) was passed and signed into federal law in 2000. The
      variations in state and federal legislation and regulations have complicated
      efforts to promote lay rescuer AED programs and in some cases have created
      impediments to such programs. Since 2000, most states have reexamined lay rescuer
      AED statutes, and many have passed legislation to remove impediments and
      encourage the development of lay rescuer AED programs. The purpose of this
      statement is to help policymakers develop new legislation or revise existing
      legislation to remove barriers to effective community lay rescuer AED programs.
      Important areas that should be considered in state legislation and regulations
      are highlighted, and sample legislation sections are included. Potential sources
      of controversy and the rationale for proposed legislative components are noted.
      This statement will not address legislation to support home AED programs. Such
      recommendations may be made after the conclusion of a large study of home AED
      use.

PMID- 16415376
TI  - Common sodium channel promoter haplotype in asian subjects underlies variability
      in cardiac conduction.
AB  - BACKGROUND: Reduced cardiac sodium current slows conduction and renders the heart
      susceptible to ventricular fibrillation. Loss of function mutations in SCN5A,
      encoding the cardiac sodium channel, are one cause of the Brugada syndrome,
      associated with slow conduction and a high incidence of ventricular fibrillation,
      especially in Asians. In this study, we tested the hypothesis that an SCN5A
      promoter polymorphism common in Asians modulates variability in cardiac
      conduction. METHODS AND RESULTS: Resequencing 2.8 kb of SCN5A promoter identified
      a haplotype variant consisting of 6 polymorphisms in near-complete linkage
      disequilibrium that occurred at an allele frequency of 22% in Asian subjects and
      was absent in whites and blacks. Reporter activity of this variant haplotype,
      designated HapB, in cardiomyocytes was reduced 62% compared with wild-type
      haplotype (P=0.006). The relationship between SCN5A promoter haplotype and PR and
      QRS durations, indexes of conduction velocity, was then analyzed in a cohort of
      71 Japanese Brugada syndrome subjects without SCN5A mutations and in 102 Japanese
      control subjects. In both groups, PR and QRS durations were significantly longer
      in HapB individuals (P< or =0.002) with a gene-dose effect. In addition, up to
      28% and 48% of variability in PR and QRS durations, respectively, were
      attributable to this haplotype. The extent of QRS widening during challenge with
      sodium channel blockers, known to be arrhythmogenic in Brugada syndrome and other
      settings, was also genotype dependent (P=0.002). CONCLUSIONS: These data
      demonstrate that genetically determined variable sodium channel transcription
      occurs in the human heart and is associated with variable conduction velocity, an
      important contributor to arrhythmia susceptibility.

PMID- 16415378
TI  - Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right
      ventricular cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an
      inherited cardiac disorder characterized by loss of cardiomyocytes and their
      replacement by adipose and fibrous tissue. It is considered a disease of cell
      adhesion because mutations in desmosomal genes, desmoplakin and plakoglobin, have
      been implicated in the pathogenesis of ARVC. In a recent report, mutations in
      plakophilin-2, a gene highly expressed in cardiac desmosomes, have been shown to
      cause ARVC. METHODS AND RESULTS: We investigated 100 white patients with ARVC for
      mutations in plakophilin-2. Nine different mutations were identified by direct
      sequencing in 11 cases. Five of these mutations are novel (A733fsX740,
      L586fsX658, V570fsX576, R413X, and P533fsX561) and predicted to cause a premature
      truncation of the plakophilin-2 protein. Family studies showed incomplete disease
      expression in mutation carriers and identified a number of individuals who would
      be misdiagnosed with the existing International Task Force and modified
      diagnostic criteria for ARVC. CONCLUSIONS: In this study, we provide new evidence
      that mutations in the desmosomal plakophilin-2 gene can cause ARVC. A systematic
      clinical evaluation of mutation carriers within families demonstrated variable
      phenotypic expression, even among individuals with the same mutation, and
      highlighted the need for a more accurate set of diagnostic criteria for ARVC.

PMID- 16415379
TI  - Impact of prosthesis-patient mismatch on long-term survival in patients with
      small St Jude Medical mechanical prostheses in the aortic position.
AB  - BACKGROUND: The impact of aortic prosthesis-patient mismatch (P-PtM) on long-term
      survival is unclear. METHODS AND RESULTS: Between 1985 and 2000, 388 patients at
      Mayo Clinic in Rochester, Minn, underwent aortic valve replacement (AVR) with 19-
      or 21-mm St Jude Medical prostheses and had transthoracic echocardiography within
      1 year after AVR. Mean age of patients was 62+/-13 years; 69% were female.
      Prosthesis effective orifice area (EOA) was derived from the continuity equation.
      P-PtM was classified as severe (indexed EOA < or =0.60 cm2/m2), moderate (0.60
      cm2/m2<indexed EOA< or =0.85 cm2/m2), or not hemodynamically significant (indexed
      EOA >0.85 cm2/m2). P-PtM was severe in 66 patients (17%), moderate in 168 (43%),
      and not hemodynamically significant in 154 (40%). Patients with severe P-PtM had
      a significantly larger body surface area (P<0.0001), higher mean gradient
      (P<0.0001), lower preoperative (P<0.0001) and postoperative (P<0.0001) ejection
      fractions, and lower stroke volume (P<0.0001) and more often received a 19-mm
      prosthesis (P=0.0008) than patients with moderate or no hemodynamically
      significant mismatch. For patients with severe mismatch, 5-year survival rates
      (72+/-6%) and 8-year survival rates (41+/-8%) were significantly less than for
      patients with moderate mismatch (80+/-3% and 65+/-5%; P=0.026) or no
      hemodynamically significant mismatch (85+/-3% and 74+/-5%; P=0.002). On
      multivariate analysis after adjustment for other predictors of outcome, severe
      mismatch was associated with higher mortality (hazard ratio 2.18; 95% confidence
      interval 1.24 to 3.85; P=0.007) and higher incidence of congestive heart failure
      (hazard ratio 3.1; 95% confidence interval 1.3 to 7.4; P=0.009) than no
      hemodynamically significant mismatch. CONCLUSIONS: Severe P-PtM is an independent
      predictor of higher long-term mortality and congestive heart failure in patients
      with small St Jude Medical aortic valve prostheses. For patients undergoing AVR
      who are at risk of severe mismatch, every effort should be made to use a larger
      prosthesis or to consider a prosthesis with a larger EOA.

PMID- 16415380
TI  - Adalimumab for treatment of cutaneous sarcoidosis.

PMID- 16415377
TI  - Effect of intensive versus standard lipid-lowering treatment with atorvastatin on
      the progression of calcified coronary atherosclerosis over 12 months: a
      multicenter, randomized, double-blind trial.
AB  - BACKGROUND: Recent clinical trials have suggested that intensive versus standard
      lipid-lowering therapy provides for additional benefit. Electron-beam computed
      tomography provides the opportunity to quantify the progression of coronary
      artery calcification (CAC) in serial measurements. METHODS AND RESULTS: In a
      multicenter, randomized, double-blind trial, 471 patients (age 61+/-8 years) who
      had no history of coronary artery disease and no evidence of high-grade coronary
      stenoses (>50% diameter reduction) were randomized if they had > or =2
      cardiovascular risk factors and moderate calcified coronary atherosclerosis as
      evidenced by a CAC score > or =30. Patients were assigned to receive 80 mg or 10
      mg of atorvastatin per day over 12 months. Progression of CAC volume scores could
      be analyzed in 366 patients. After pretreatment with 10 mg of atorvastatin for 4
      weeks, 12 months of study medication reduced LDL cholesterol from 106+/-22 to
      87+/-33 mg/dL in the group randomized to receive 80 mg of atorvastatin (P<0.001),
      whereas levels remained stable in the group randomized to receive 10 mg (108+/-23
      at baseline, 109+/-28 mg/dL at the end of the study, P=NS). The mean progression
      of CAC volume scores, corrected for the baseline CAC volume score, was 27% (95%
      CI 20.8% to 33.1%) in the 80-mg atorvastatin group and 25% (95% CI 19.1% to
      30.8%) in the 10-mg atorvastatin group (P=0.65). CAC progression showed no
      relationship with on-treatment LDL cholesterol levels. CONCLUSIONS: We did not
      observe a relationship between on-treatment LDL cholesterol levels and the
      progression of calcified coronary atherosclerosis. Over a period of 12 months,
      intensive atorvastatin therapy was unable to attenuate CAC progression compared
      with standard atorvastatin therapy. The possibility remains that the time window
      was too short to demonstrate an effect.

PMID- 16415381
TI  - Thalidomide for the treatment of refractory necrobiosis lipoidica.

PMID- 16415383
TI  - Defining urticarial dermatitis: a subset of dermal hypersensitivity reaction
      pattern.
AB  - BACKGROUND: Urticarial dermatitis may represent a useful term for a subset of a
      reaction pattern designated most commonly as dermal hypersensitivity by
      pathologists. The term is not commonly used, and requires definition to determine
      whether it is clinically relevant. OBJECTIVES: To define urticarial dermatitis
      and distinguish it from other urticarial reaction patterns and to review the
      frequency with which dermatologists can recognize clinical settings that match
      the biopsy findings of urticarial dermatitis. DESIGN: Retrospective analysis of
      clinical and/or histological diagnosis of urticarial dermatitis, applying strict
      histological criteria in a center using urticarial dermatitis as a diagnostic
      term in 190 archived reports. SETTING: Tertiary referral dermatopathology service
      reporting for dermatological practices in Sydney, Australia. MAIN OUTCOME
      MEASURES: The correlation between clinical and histological diagnoses of
      urticarial dermatitis and alternate diagnoses was analyzed. The frequency of
      positive immunofluorescence findings for bullous pemphigoid was determined in a
      subset of patients with urticarial dermatitis in whom this test was ordered to
      exclude prodromal bullous pemphigoid. RESULTS: Urticarial dermatitis was the
      histological diagnosis in at least 1 biopsy result in 148 patients, and matched
      the provisional clinical diagnosis in 49 (33.1%) patients. Urticarial dermatitis
      was the only diagnosis provided in 21 patients. The main alternate clinical
      diagnoses provided were early bullous pemphigoid or dermatitis herpetiformis (47
      patients [31.8%]), dermatitis (39 patients [26.4%]), drug reaction (35 patients
      [23.6%]), urticarial vasculitis (24 patients [16.2%]), and urticaria (12 patients
      [8.1%]). In 91 patients with a clinical diagnosis of urticarial dermatitis, the
      histological diagnosis in at least 1 biopsy result was matched in 49 patients
      (53.8%); other histological diagnoses included dermatitis (21 patients [23.1%]),
      papular urticaria (12 patients [13.2%]), drug reaction (6 patients [6.6%]), and
      urticaria (3 patients [3.3%]). Review of 38 direct immunofluorescent results for
      prodromal bullous pemphigoid and a biopsy finding of urticarial dermatitis
      revealed only 3 positive results (7.9%). CONCLUSIONS: Urticarial dermatitis seems
      to be a useful histological and clinical term for a subset of the dermal
      hypersensitivity reaction pattern. Although the clinical presentation is not
      restricted to a specific entity, eczema and drug reactions seem to be the most
      frequent clinical associations; and in a subset of patients, urticarial
      dermatitis remains as a recognizable reaction pattern. Urticarial dermatitis
      without eosinophilic spongiosis is not a reliable indicator for bullous
      pemphigoid, because the findings of immunofluorescence are often negative.

PMID- 16415382
TI  - Tzanck smear as a rapid diagnostic tool for disseminated cryptococcal infection.

PMID- 16415384
TI  - Cross-sectional study of bisphosphonate use in dermatology patients receiving
      long-term oral corticosteroid therapy.
AB  - OBJECTIVE: To examine whether patients had received bisphosphonates at the
      beginning of planned long-term glucocorticoid therapy, which is recommended by
      the guidelines from the American College of Rheumatology to prevent
      glucocorticoid-induced osteoporosis, prior to referral to a tertiary dermatology
      clinic. DESIGN: Cross-sectional study. SETTING: Tertiary referral center.
      PATIENTS: We reviewed 35 patients from an established cohort of patients referred
      with chronic skin diseases that require prolonged glucocorticoid use. MAIN
      OUTCOME MEASURE: The use of osteoporosis prophylaxis was determined by medical
      chart review and communication with patients. RESULTS: Of 35 patients, 28 (80%)
      were not receiving any bisphosphonates at referral. These patients began
      glucocorticoid therapy 17 months (median, 6 months; range, 1-102 months) prior to
      referral. The proportion of patients treated with bisphosphonates in our cohort
      did not change after the guidelines of the American College of Rheumatology were
      published. CONCLUSIONS: For patients of non-child-bearing potential with
      dermatological diseases in which prolonged oral corticosteroid treatment is
      anticipated, bisphosphonates should be prescribed concomitantly with the
      initiation of glucocorticoid therapy.

PMID- 16415385
TI  - Consistent cutaneous imaging with commercial digital cameras.
AB  - OBJECTIVE: To demonstrate how to improve the reproducibility and accuracy of
      digital images of the skin taken with commercially available digital cameras by
      transforming them to a standard color space, sRGB. METHODS: Our computer
      algorithm transforms digital images to the standard sRGB color space. It is based
      on a card with a number of color squares with known colorimetric properties that
      is included in the image, thereby removing any ambiguity about the color
      information in the image. Reproducibility and accuracy of the method were
      assessed by comparing images of color squares with known colorimetric properties
      taken with different digital cameras at different exposures and zoom settings.
      RESULTS: Although calibrated images exhibit markedly improved precision and
      accuracy compared with noncalibrated images, all variability of the imaging
      process cannot be eliminated. CONCLUSION: With a little care and effort, a
      calibrated color chart, and computer software, it is possible to greatly improve
      the quality of clinical imaging in dermatology and possibly other fields of
      medicine.

PMID- 16415386
TI  - Acute-onset, painful acral granuloma annulare: a report of 4 cases and a
      discussion of the clinical and histologic spectrum of the disease.
AB  - BACKGROUND: Granuloma annulare is a benign cutaneous inflammatory disease of
      unknown etiology most commonly presenting on the hands and feet and consisting of
      asymptomatic to mildly pruritic, flesh-colored to erythematous annular plaques.
      To our knowledge, an acute-onset, painful acral eruption has not been previously
      recognized. OBSERVATIONS: We report 4 patients who presented with acute-onset,
      painful acral granuloma annulare. CONCLUSIONS: It is possible for granuloma
      annulare to present as a painful eruption with an acute onset and an acral
      distribution. Biopsy results are a crucial factor when establishing the diagnosis
      of this atypical clinical presentation of granuloma annulare.

PMID- 16415387
TI  - The relationship between neutrophilic dermatosis of the dorsal hands and sweet
      syndrome: report of 9 cases and comparison to atypical pyoderma gangrenosum.
AB  - BACKGROUND: Neutrophilic dermatoses are a collection of diseases with varying
      presentation unified by clinical and histologic features. Neutrophilic dermatosis
      of the dorsal hands is a recently described clinical entity and an evolving
      disease concept. Its relationship to acute febrile neutrophilic dermatosis (Sweet
      syndrome), pyoderma gangrenosum, and a primary vasculitis has been debated.
      OBSERVATIONS: We present 9 cases (8 women and 1 man) of neutrophilic dermatosis
      of the dorsal hands, all with consistent histologic features. Two cases had
      histologic evidence of vasculitis, and 3 had clinical extension of lesions onto
      the forearms. Most showed fever, leukocytosis, and/or elevated erythrocyte
      sedimentation rate. Individual cases were associated with leukemia, lung
      carcinoma, and inflammatory bowel disease. All 9 patients responded to systemic
      corticosteroid therapy, with additional response to dapsone, methotrexate, and
      potassium iodide therapies in several cases. Of the 9 patients, 5 showed complete
      resolution of their skin disease, whereas 4 required ongoing therapy. We assessed
      the 43 cases previously reported in the literature. CONCLUSION: The clinical
      presentation, laboratory data, histologic features, and response to
      corticosteroid therapy offer strong evidence that neutrophilic dermatosis of the
      dorsal hands is a localized variant of Sweet syndrome and is also identical to
      atypical pyoderma gangrenosum when that condition presents on the hands.

PMID- 16415388
TI  - Mycophenolate mofetil as an effective corticosteroid-sparing therapy for
      recalcitrant dermatomyositis.
AB  - BACKGROUND: Dermatomyositis (DM) is a multisystem idiopathic inflammatory
      disorder that most commonly affects the muscles and skin. Systemic
      corticosteroids are the mainstay of therapy but are limited by their long-term
      adverse effects. OBSERVATIONS: We sought to evaluate the effectiveness of oral
      mycophenolate mofetil in patients with cutaneous lesions of DM recalcitrant to
      other therapies through an open-label retrospective medical chart review of
      patients in a university-affiliated private practice setting. Twelve patients
      with DM who had skin lesions recalcitrant to traditional therapies or who
      developed toxic effects from traditional therapies began mycophenolate mofetil
      treatment at doses ranging from 500 mg to 1 g twice a day. Response was based on
      improvement in skin disease as judged clinically, an increase in strength, and/or
      an ability to decrease or discontinue concomitant therapies. Improvement was seen
      in 10 of the 12 patients, most within 4 to 8 weeks. Most patients tolerated
      mycophenolate mofetil treatment without problem; however, 1 patient developed a B
      cell lymphoma of the central nervous system, and another developed abnormal
      levels of hepatic enzymes along with urinary symptoms. Resolution of these toxic
      reactions occurred with cessation of mycophenolate mofetil treatment in each
      patient. CONCLUSION: Mycophenolate mofetil may be an effective corticosteroid
      sparing therapy for the treatment of some patients with DM.

PMID- 16415389
TI  - Improvement in dermatomyositis rash associated with the use of antiestrogen
      medication.
AB  - BACKGROUND: Dermatomyositis (DM) is an autoimmune disorder that occurs more often
      in women than men and causes highly symptomatic and inflammatory cutaneous and
      proximal muscle disease. Corticosteroids have been the treatment of choice for
      myositis in DM, and antimalarial agents for the skin disease of DM, with
      methotrexate sodium, azathioprine, mycophenolate mofetil, cyclosporine, and
      intravenous immunoglobulin used as steroid-sparing agents. Recently, reports
      supporting a role for anti-tumor necrosis factor alpha (TNF-alpha) therapy in the
      treatment of DM have emerged. OBSERVATIONS: We describe 2 women who experienced
      an improvement in their DM-associated skin eruptions while taking antiestrogen
      medication. The first patient was taking tamoxifen, a selective estrogen receptor
      modulator that has been found to have anti-TNF-alpha properties. The second was
      taking anastrozole, an aromatase inhibitor. When tamoxifen therapy was
      discontinued after 4 years of use in the first patient, her DM rash worsened and
      remained difficult to control with conventional immunosuppressant medication.
      CONCLUSIONS: With the limited number of therapies available to manage DM skin
      eruptions, the discovery of novel agents effective in treating this disease is
      vital. Using antiestrogen medication in women with DM may result in a significant
      improvement in their rash, possibly via the inhibition of TNF-alpha production by
      immune or other cells. Further investigation into the use of antiestrogen therapy
      in DM is merited to evaluate long-term risks and benefits.

PMID- 16415390
TI  - Warfarin therapy for livedoid vasculopathy associated with cryofibrinogenemia and
      hyperhomocysteinemia.
AB  - BACKGROUND: Livedoid vasculopathy is an idiopathic, chronic disorder manifested
      by painful, purpuric macules on the lower extremities that superficially
      ulcerate, resulting in atrophic, stellate scars with peripheral telangiectasias
      and hyperpigmentation. OBSERVATIONS: A 50-year-old man presented with recurrent,
      painful ulcerations on the medial aspect of his malleoli and calves. The clinical
      presentation, histologic findings, and results of laboratory evaluation confirmed
      the diagnosis of livedoid vasculopathy in this case. Despite being refractory to
      treatment with multiple other medications, the lesions responded dramatically to
      oral warfarin sodium therapy. CONCLUSION: Treatment with warfarin may be a
      beneficial therapy for patients with livedoid vasculopathy.

PMID- 16415392
TI  - The era of cooperation.

PMID- 16415391
TI  - Glucocorticoid-induced bone loss in dermatologic patients: an update.
AB  - OBJECTIVE: To raise awareness of the new treatment options and current
      recommendations among dermatologists treating patients with systemic
      corticosteroids. DATA SOURCES: MEDLINE peer-reviewed publications. STUDY
      SELECTION: English language and clinical pertinence to corticosteroid-induced
      osteoporosis. DATA EXTRACTION: Pertinent information on pathophysiologic,
      epidemiologic, clinical trial, cost-effectiveness, and treatment option data
      regarding corticosteroid-induced osteoporosis. DATA SYNTHESIS: Comprehensive
      summary of published data on the pathophysiologic, epidemiologic, clinical, and
      treatment data and current practice guidelines regarding corticosteroid-induced
      osteoporosis; creation of an algorithmic management approach for patients treated
      with long-term oral corticosteroids. CONCLUSIONS: Glucocorticoid-induced bone
      loss is the most predictable and debilitating complication of prolonged
      administration of systemic corticosteroids. Every dermatologist prescribing
      systemic corticosteroids must be aware of corticosteroid-induced osteoporosis and
      ensure that every patient is receiving general measures to prevent it. Despite
      efficacious preventive and therapeutic options, actual implementation of these
      strategies remains unacceptably low. Based on currently available evidence, the
      first choice for prevention and treatment of glucocorticoid-induced osteoporosis
      should be a potent oral bisphosphonate such as alendronate (70 mg/wk) or
      risedronate sodium (35 mg/wk). For patients with severe osteoporosis or patients
      with active osteoporotic fractures, the anabolic agent teriparatide (recombinant
      fragmented parathyroid hormone) should be considered as a first-line option for
      up to 2 years.

PMID- 16415393
TI  - The clinical image: archiving clinical processes and an entire specialty.

PMID- 16415394
TI  - Asymptomatic lesions on the hands.

PMID- 16415396
TI  - Breast erythema and induration in a 77-year-old woman.

PMID- 16415395
TI  - A papule arising in irradiated breast tissue.

PMID- 16415397
TI  - Chronic foot infection in a Mexican immigrant.

PMID- 16415398
TI  - Liver enzyme abnormalities in patients with atopic dermatitis treated with
      mycophenolate mofetil.

PMID- 16415399
TI  - Validating standardized acquisition of digital dermatologic images for use in the
      national health and nutrition examination survey.

PMID- 16415400
TI  - Alopecia impairs the quality of life of patients with lupus erythematosus.

PMID- 16415402
TI  - An unusual presentation of amyopathic dermatomyositis associated with fatal
      interstitial lung disease.

PMID- 16415401
TI  - Dermatomyositis and nasopharyngeal carcinoma: report of 8 cases.

PMID- 16415403
TI  - Infliximab-induced lupus erythematosus tumidus in a patient with rheumatoid
      arthritis.

PMID- 16415405
TI  - The Department of Surgery, Indiana University School of Medicine, Indianapolis.

PMID- 16415404
TI  - Dermoscopy of atypical dermatofibroma: central white network.

PMID- 16415406
TI  - Changes in breathing control and mechanics after laparoscopic vs open
      cholecystectomy.
AB  - HYPOTHESIS: We hypothesized that there might be different effects on breathing
      control and respiratory mechanics after laparoscopic vs open cholecystectomy.
      DESIGN: Randomized clinical trial. SETTING: A general hospital in Greece.
      PATIENTS: Of 53 patients assessed for eligibility, 18 and 10 were randomly
      allocated to the laparoscopic and open cholecystectomy groups, respectively.
      These 28 patients had normal spirometry measurements and American Society of
      Anesthesiologists' class I physical status. MAIN OUTCOME MEASURES: Measurements
      of breathing control and mechanics variables. Tidal volume, inspiratory time,
      breathing frequency, mean inspiratory flow, duty cycle, central respiratory
      drive, and mean inspiratory impedance were recorded before surgery on the second
      and eighth postoperative days. Airway resistance was recorded before surgery and
      on the eighth postoperative day, with all measurements being performed under no
      influence of analgesia. RESULTS: Two days after surgery, inspiratory time,
      breathing frequency, and central respiratory drive were significantly changed
      compared with preoperative values for both methods, whereas mean inspiratory
      impedance was significantly increased (P<.001) for the laparoscopic procedure.
      Eight days after surgery, changes were seen only for the laparoscopic group: duty
      cycle and airway resistance were significantly reduced (P = .01) and increased (P
      = .04), respectively, compared with preoperative data. CONCLUSION: Laparoscopic
      cholecystectomy seems to be associated with small but sustained alterations in
      the control of breathing and mechanics, which might have an unfavorable clinical
      impact on patients with compromised lung function.

PMID- 16415407
TI  - Role of the rectosigmoidal junction in fecal continence: concept of the primary
      continent mechanism.
AB  - HYPOTHESIS: At mass contraction of the descending colon, the colonic contents
      stop at the sigmoid colon (SC) and do not pass directly to the rectum. We
      investigated the hypothesis that a continent mechanism seems to exist at the
      rectosigmoidal junction (RSJ), preventing the direct passage of stools from the
      descending colon to the rectum. METHODS: The SC in 16 healthy volunteers (mean +/
      SD age, 38.6 +/- 10.2 years; 9 men and 7 women) was distended with an isotonic
      sodium chloride solution-filled balloon, and the pressure response of the RSJ and
      the rectum was recorded at rapid and gradual filling of the balloon. The test was
      repeated after the SC and RSJ were anesthetized separately. RESULTS: Rapid SC
      balloon distension with a mean +/- SD of 52.1 +/- 3.6 mL of isotonic sodium
      chloride solution effected an RSJ pressure increase to a mean +/- SD of 67.8 +/-
      18.4 cm H(2)O (P<.01) with no rectal pressure response (P>.05). Slow SC filling
      produced a progressive increase in RSJ pressure but no rectal pressure change. At
      a mean +/- SD SC distending volume of 86.3 +/- 4.1 mL, the RSJ pressure decreased
      to 9.6 +/- 2.8 (P<.01), and the balloon was dispelled to the rectum; rectal
      pressure increased (P<.001), and the balloon was expelled to the exterior. The
      RSJ pressure did not respond to distension of the anesthetized SC. CONCLUSIONS:
      Contraction of the RSJ at rapid SC distension with big volumes implies a reflex
      relationship that we call the RSJ guarding reflex. This reflex seems to prevent
      the descending colon contents from passing directly to the rectum. It is
      considered the first continent reflex and may serve as an investigative tool in
      the study of fecal incontinence.

PMID- 16415408
TI  - Creating arteriovenous fistulas in 132 consecutive patients: exploiting the
      proximal radial artery arteriovenous fistula: reliable, safe, and simple forearm
      and upper arm hemodialysis access.
AB  - HYPOTHESIS: Dialysis by native arteriovenous fistula (NAVF) clearly offers lower
      infection rates, fewer procedures, and lower mortality risk compared with access
      by catheter or graft, in addition to lower cost. However, NAVFs are utilized for
      vascular access in only 30% of hemodialysis patients in the United States. Wrist
      NAVFs are not feasible or successful in many patients and upper arm brachial
      artery NAVFs may be impractical or lead to additional procedures or
      complications. Careful preoperative evaluation of all options for NAVF
      construction including the proximal radial artery (PRA) as an arterial inflow
      site will find most, if not all, patients to be candidates for successful NAVFs.
      DESIGN: Retrospective review of consecutive operations for hemodialysis access
      preformed by an individual surgeon from May 2003 to November 2004. SETTING: Two
      university-affiliated tertiary medical centers. PATIENTS: All patients underwent
      preoperative ultrasound evaluation by the operating surgeon. A wrist fistula was
      first choice for access when success was predicted by ultrasound and physical
      examination. The second choice, and most common operation, was a PRA NAVF with
      distal forearm (retrograde) flow established by disrupting the initial venous
      valve using a vessel probe. RESULTS: One hundred thirty-two patients aged 11 to
      90 years (mean = 61) were reviewed. Sixty-eight patients had diabetes and 61 were
      female. Thirty-four had previous failed access surgery. Native arteriovenous
      fistulas were created in all patients. No grafts were used. A PRA NAVF was
      utilized in 105 operations. Overall (assisted) patency was 97%, with a mean
      follow-up of 11 months. Importantly, there were no infections or hospitalizations
      due to the NAVF access operations. CONCLUSIONS: No grafts were used in this
      series of 132 consecutive patients. The PRA NAVF was the most common operation
      and an important addition to wrist, brachial, and transposition fistulas.
      Proximal radial artery NAVFs increase the opportunity for construction of
      successful NAVFs and are reliable, safe, and simple procedures with access sites
      often available in both the forearm and in the upper arm.

PMID- 16415409
TI  - Parathyroid graft function after presternal subcutaneous autotransplantation for
      renal hyperparathyroidism.
AB  - HYPOTHESIS: Presternal subcutaneous autotransplantation of parathyroid tissue
      after total parathyroidectomy for renal hyperparathyroidism could be at least as
      effective as intramuscular grafting, without its complications. DESIGN:
      Prospective study of a postoperative diagnostic method of monitoring intact
      parathyroid hormone (iPTH) levels among a cohort of surgical patients, without
      loss to follow-up. SETTING: Hemodialysis unit in a university hospital. PATIENTS:
      Twenty-five patients (17 women and 8 men) underwent total parathyroidectomy and
      presternal subcutaneous autotransplantation for renal hyperparathyroidism at
      Donostia Hospital, San Sebastian, Spain, between January 1, 2002, and June 30,
      2004. MAIN OUTCOME MEASURES: Evaluation of parathyroid graft function by
      measurement of serum iPTH levels at admission and 24 hours and 1, 3, 5, 15, 30,
      and 60 weeks after surgery. RESULTS: The mean +/- SD preoperative serum iPTH
      level was 1302 +/- 425 pg/mL; the iPTH level was undetectable in all patients 24
      hours after surgery. Subsequent mean +/- SD iPTH levels obtained were 14 +/- 10
      pg/mL after 1 week, 54 +/- 1 pg/mL after 5 weeks, 64 +/- 9 pg/mL after 15 weeks,
      77 +/- 8 pg/mL after 30 weeks, and 106 +/- 21 pg/mL after 60 weeks.
      Autotransplanted parathyroid tissue appears to be adequately functional at week 5
      (criterion level of adequate functioning, 50 pg/mL). CONCLUSIONS: Presternal
      subcutaneous autotransplantation after total parathyroidectomy for renal
      hyperparathyroidism may be an alternative to avoid musculus brachialis grafting
      and its complications. Our functional results compare favorably with the
      published data on other surgical techniques for the treatment of renal
      hyperparathyroidism. Long-term follow-up of this series is planned.

PMID- 16415410
TI  - A double-blind randomized controlled trial of toremifen therapy for mastalgia.
AB  - HYPOTHESIS: Toremifen is effective in reducing breast pain and does not increase
      the incidence of adverse events as a therapy for moderate to severe mastalgia.
      DESIGN AND PATIENTS: In a double-blind randomized controlled trial, patients with
      moderate to severe mastalgia received toremifen citrate, 30 mg daily, or a
      placebo tablet for 3 menstrual cycles and were followed up for breast pain score
      and adverse events. The serum levels of estradiol, progesterone, and prolactin
      were examined before treatment and correlated with the response rate to toremifen
      treatment. RESULTS: Seventy-two (69.2%) of 104 patients receiving toremifen and
      29 (31.9%) of 91 receiving placebo responded to the treatment, with reduction in
      breast pain score of more than 50% (P<.001). Among the patients with cyclical
      mastalgia, the response rate for toremifen was 76.7% (59/77), whereas the
      response rate for placebo was 34.8% (23/66; P<.001). In contrast, the response
      rate of patients with noncyclical mastalgia was 48.1% (13/27) for toremifen and
      24.0% (6/25) for placebo (P = .09). Adverse events were observed in 44 (42.9%) of
      104 patients receiving placebo and 46 (50.5%) of 91 patients receiving toremifen
      (P = .45). A positive correlation between baseline breast pain score and serum
      estradiol level was observed in patients with cyclical mastalgia (r = 0.35, P =
      .003). CONCLUSIONS: Toremifen effectively relieves moderate and severe cyclical
      mastalgia and tends to exert a positive therapeutic effect on noncyclical
      mastalgia. In addition, toremifen therapy does not increase the incidence of
      intolerable adverse event. Therefore, it is a feasible therapy for mastalgia,
      especially cyclical mastalgia.

PMID- 16415411
TI  - High incidence of extrapancreatic neoplasms in patients with intraductal
      papillary mucinous neoplasms.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are associated with
      a high incidence of extrapancreatic neoplasms. DESIGN: Retrospective study.
      SETTING: Tertiary care referral center. PATIENTS: Sixty-one patients underwent
      surgical resection for IPMN between January 1, 1993, and June 30, 2004. Thirty
      eight patients with mucinous cystic neoplasms and 50 patients with pancreatic
      ductal adenocarcinoma also were examined for development of extrapancreatic
      neoplasms. MAIN OUTCOME MEASURES: The incidence and clinicopathological features
      of extrapancreatic neoplasms with IPMNs were compared with those with mucinous
      cystic neoplasm and pancreatic ductal adenocarcinoma. RESULTS: Of the 61 patients
      with IPMNs, 24 (39%) developed 26 extrapancreatic neoplasms, and 18 (30%) had
      extrapancreatic malignancies. Gastric adenocarcinoma (33%) and colorectal
      adenocarcinoma (17%) were the most common neoplasms in the 24 patients. During
      postoperative follow-up, 3 patients died of malignant IPMNs, 3 of associated
      malignancies, and 1 of a nonmalignancy-related cause. Comparisons of the
      clinicopathological features in patients with IPMNs with and without associated
      malignancies revealed no significant differences in age, sex, family history of
      malignancy, history of cigarette smoking or alcohol abuse, or type of IPMN. The
      incidence of extrapancreatic neoplasms in patients with IPMN was significantly
      higher than in those with other pancreatic diseases such as mucinous cystic
      neoplasm (8%) or pancreatic ductal adenocarcinoma (10%). CONCLUSIONS: Frequently,
      IPMNs are associated with the development of extrapancreatic neoplasms.
      Considerable attention should be paid to the possible occurrence of other
      associated malignancies in patients with IPMNs, either concurrently or
      postoperatively. Further molecular studies may be necessary to elucidate the
      unusual association between IPMN and other primary neoplasms.

PMID- 16415412
TI  - Laparoscopic ventral hernia repair in obese patients: a new standard of care.
AB  - HYPOTHESIS: Ventral abdominal hernias represent a frequent and often formidable
      clinical problem, especially in obese patients. Because laparoscopic ventral
      hernia repair (LVHR) results in few complications and a low recurrence rate, the
      use of minimally invasive techniques in this subgroup of patients may minimize
      perioperative complications and failure rates. DESIGN: Retrospective review of
      prospectively collected data. SETTING: Tertiary care hospital. PATIENTS: One
      hundred sixty-three obese patients (body mass index [calculated as weight in
      kilograms divided by the square of height in meters], > or =30) who underwent
      LVHR at our institution between July 1, 1998, and December 31, 2003.
      INTERVENTION: Laparoscopic ventral hernia repair with an expanded
      polytetrafluoroethylene mesh. MAIN OUTCOME MEASURES: Patient age, sex, body mass
      index, size of fascial defect and mesh, operating time, operative blood loss,
      length of hospitalization, complications, and hernia recurrences. RESULTS: Ninety
      eight women and 65 men, with a mean body mass index of 38, underwent LVHR. Twenty
      patients (12.3%) had 21 postoperative complications. There was no perioperative
      mortality. The mean length of hospital stay was 2.6 days. The recurrence rate was
      5.5% at a mean follow-up of 25 months (range, 1-73 months). CONCLUSIONS: A low
      rate of conversion to laparotomy, minimal perioperative morbidity, and the
      absence of perioperative mortality in this series indicate the safety of LVHR in
      obese patients with complex hernias. In addition, a success rate of more than
      94.5% suggests improved efficacy of LVHR compared with the historical rates among
      control subjects undergoing open surgery. In experienced hands, LVHR may be the
      approach of choice for most patients with a body mass index of 30 or more.

PMID- 16415413
TI  - Interdisciplinary work flow assessment and redesign decreases operating room
      turnover time and allows for additional caseload.
AB  - HYPOTHESIS: Operating room turnover time (TOT) and daily caseload can be improved
      by analyzing the routine tasks of the operating team and minimizing
      inefficiencies. DESIGN: In this prospective study, the assigned tasks and work
      flow patterns of the anesthesiologist, circulating nurse, and surgical
      technologist during operations and operating room turnover were studied and
      changes were implemented where inefficiencies were observed. A brief pilot
      followed by a broader-scale study was conducted. SETTING: Tertiary care center.
      PARTICIPANTS: Circulating nurses and surgical technicians were routinely assigned
      to work with one anesthesiologist and one surgeon during the pilot study; 4
      surgeons and 32 anesthesiologists participated in the follow-up study.
      INTERVENTIONS: The work flow diagram of each individual was redrawn, and changes
      were implemented. Critical moments were identified, in which brief assistance
      from other personnel was needed to improve efficiency. MAIN OUTCOME MEASURES:
      Operative TOT and number of daily operations were the main outcomes. A 2-tailed t
      test was used to compare the TOTs; chi(2) analysis was used to compare the number
      of cases completed. Significance was defined as P<.05. RESULTS: A total of 401
      operations and 253 turnovers were evaluated. Redesign decreased operating room
      TOT from 43.7 to 27.7 minutes (P<.001). The mean number of cases completed per
      day increased from 1.78 to 2.34 (P<.001). CONCLUSION: Interdisciplinary work flow
      assessment and redesign resulted in decreased operating room TOTs and additional
      cases being completed each day for 4 different surgeons.

PMID- 16415414
TI  - National trends in bariatric surgery, 1996-2002.
AB  - BACKGROUND: Surgical therapy for the long-term treatment of obesity ("bariatric
      surgery") in individuals whose body mass index (calculated as weight in kilograms
      divided by the square of height in meters) is 40 or higher or in those who have
      significant obesity-related comorbidities and a body mass index of 35 or higher
      is one of few interventions shown to be effective. Many aspects of recent
      national bariatric surgery trends are unclear, including the ages of individuals
      undergoing such procedures and the economic burden borne by public vs private
      payers. HYPOTHESIS: Population-adjusted rates of bariatric surgery are rapidly
      increasing and have economic implications that differ for private vs public
      payers. DESIGN AND SETTING: We examined hospitalization and charge data from the
      Nationwide Inpatient Sample from 1996 through 2002, representative of national
      patterns for children and adults. We derived nationally weighted estimates of
      population-adjusted hospitalization rates and inflation-adjusted charges for
      bariatric surgery. We also examined the relative economic burden for public vs
      private payers for bariatric surgery discharges. RESULTS: Population-adjusted
      rates of bariatric surgery in the overall sample increased more than 7-fold in
      the study period, from 3.5 per 100 000 US population in 1996 to 24.0 per 100 000
      in 2002. During this period, among youth (<20 years old), rates increased from
      0.23 per 100 000 to 0.73 per 100 000; and among elderly persons (>65 years old),
      rates increased from 0.30 per 100 000 to 1.69 per 100 000. The rate increased
      most dramatically among those aged 20 to 65 years, who composed 97% or more of
      bariatric surgery discharges annually. Increases in bariatric surgical volume
      corresponded with increasing economic consequences overall, exceeding USD $2
      billion in annual charges by 2002 (mean, USD $29,107 per discharge). Since 2000,
      private payers have been charged for more than 80% of the national total; annual
      charges to Medicare and Medicaid have been comparatively modest, but each
      exceeded USD $100 million by 2002. CONCLUSIONS: National rates of bariatric
      surgery have increased markedly among children and adults, with attendant
      economic consequences, principally for private insurers. This trend may reflect
      the dearth of effective primary care and preventive interventions to address the
      obesity epidemic.

PMID- 16415415
TI  - Prevalence of meperidine use in older surgical patients.
AB  - HYPOTHESIS: The unique toxic and adverse effects of meperidine hydrochloride have
      prompted a number of expert panels convened by national health care policy
      organizations to recommend that meperidine not be used in older patients. We
      hypothesized that the prescription of meperidine was less likely to reflect these
      recommendations in older surgical patients than in older medical patients. The
      current study examined the use of meperidine in 2 urban hospitals as 1 quality
      indicator of the care of older adults, measuring the prevalence of its use and
      characteristics of the patients to whom it is administered. DESIGN: Retrospective
      analysis. SETTING: Two urban hospitals: a large private tertiary care teaching
      hospital and a smaller academically affiliated Veterans Affairs medical center.
      PATIENTS: Patients 65 years or older and hospitalized on medical and surgical
      services between February 19, 2001, and February 14, 2003. MAIN OUTCOME MEASURES:
      Patient demographics, medication administration, and department of admitting
      physician. RESULTS: Meperidine was administered to approximately 1 in 8 older
      surgical patients at both institutions. Surgical patients were more likely than
      medical patients to receive a dose of meperidine (hospital A, 12.2% vs 4.3%,
      P<.001; hospital B, 12.9% vs 1.9%, P<.001). Of those administered meperidine,
      surgical patients were also more likely than medical patients to receive multiple
      doses (hospital A, 86.0% vs 65.5%, P = .045; hospital B, 73.8% vs 48.4%, P =
      .02). CONCLUSIONS: Contrary to national recommendations, meperidine continues to
      be administered to many hospitalized older adults, particularly those on surgical
      services. Several alternatives to meperidine exist that provide equal or better
      pain relief with fewer toxic effects. Hospitals and, in particular, departments
      of surgery should address this cause of preventable morbidity in this vulnerable
      population.

PMID- 16415416
TI  - Increased mortality and morbidity associated with thyroidectomy for intrathoracic
      goiters reaching the carina tracheae.
AB  - HYPOTHESIS: Complications associated with thyroidectomy for intrathoracic goiters
      have been underestimated because of the lack of a precise definition of high-risk
      patients. DESIGN: Retrospective multicenter multinational review of medical
      records and radiographic images of patients who underwent thyroidectomy for
      intrathoracic goiters reaching the carina tracheae. Demographic, clinical,
      operative, anatomical, and pathological data were recorded. RESULTS: There were
      35 patients (mean +/- SE age, 63 +/- 11 years) included in the study. In 4
      patients, the goiter was asymptomatic; 10 patients had dysphagia, 24 patients had
      dyspnea, and 3 patients had superior vena cava syndrome. A median sternotomy was
      required in 12 patients and a right-sided thoracotomy in 1 patient. The mean +/-
      SE operative time was 145 +/- 72 minutes (range, 50-360 minutes). Transient
      hypoparathyroidism developed in 13 patients. Four patients experienced transient
      hoarseness, and 1 patient had permanent vocal cord paralysis. There were no
      significant differences between the proportion of patients who underwent or did
      not undergo sternotomy or thoracotomy regarding vocal cord dysfunction (2 [15%]
      of 13 patients vs 3 [13%] of 22 patients) or hypoparathyroidism (5 [38%] of 13 vs
      6 [28%] of 22 patients). The mean postoperative hospital stay was 10 days (range,
      2-84 days). Four patients required reoperation. Two patients died. Nine of 14
      patients with thyroid glands weighing at least 260 g required sternotomy vs 3 of
      14 patients with thyroid glands weighing less than 260 g (P = .02). Overall, 18
      [52%] of 35 patients were discharged without any complication. CONCLUSION:
      Intrathoracic goiters reaching the carina tracheae carry a high unreported risk
      of sternotomy, postoperative complications, reoperation, and death.

PMID- 16415417
TI  - Patient-centered informed consent in surgical practice.
AB  - OBJECTIVES: To review the medical, ethical, and legal basis of the doctrine of
      informed consent for surgery and its complications, particularly for an
      incapacitated patient who requires a surrogate decision maker; to discuss the
      elasticity of the consent doctrine, whether surgical consent encompasses consent
      for surgical complications, and emphasize the importance of communication and
      shared decision making in the context of the patient-surgeon relationship; and to
      discuss patient and surrogate refusal of treatment, standards of surrogate
      decision making, barriers to effective communication, the role of the hospital
      ethics committee in resolving disputes over treatment, and how to reconceptualize
      surgical consent in the context of patient-centered medicine. DATA SOURCES: We
      reviewed PubMed citations for informed consent in surgery, patient-physician
      communication, shared decision making, patient-centered medicine, and consent
      guidelines published by specialty societies, particularly the American College of
      Surgeons and the Society for Critical Care Medicine. STUDY SELECTION: We selected
      articles in which issues of consent for surgical treatment were discussed or
      measured. DATA EXTRACTION: We extracted data relevant to questions of consent in
      surgical practice. DATA SYNTHESIS: We studied qualitative aspects of the consent
      doctrine. CONCLUSIONS: Surgical consent is not an event or a signature on a form
      but is an ongoing process of communication that continues throughout
      preoperative, perioperative, and postoperative care. In the context of patient
      centered medicine, consent is best conceptualized as shared decision making with
      patients or their surrogates.

PMID- 16415418
TI  - Colon cancer metastatic to the lung and the thyroid gland.
AB  - The clinical diagnosis of primary thyroid cancer is uncommon, constituting 1.5%
      of all cancers in the United States. Clinically diagnosed metastatic cancer to
      the thyroid gland is rare. Colon cancer is one of the most common cancers in the
      United States, with a high propensity to metastasize; 30% to 40% of patients have
      metastatic disease at the initial diagnosis. The most common sites of metastasis
      from colon cancer are the regional lymph nodes, the liver, the lung, and the
      peritoneum. Colon cancer metastasis to the thyroid gland is rare, with only a few
      reported cases, mainly in the pathology literature. These cases describe
      metastasis from colon cancer to the thyroid gland that became apparent years
      after the initial diagnosis of colon cancer and were usually associated with
      dissemination to the liver, the lung, or both. We report a case of colonic
      adenocarcinoma metastatic to the thyroid gland and lung without involvement of
      the liver. A review of the literature is also included.

PMID- 16415419
TI  - Ileal perforation secondary to Clostridium difficile enteritis: report of 2
      cases.
AB  - Two cases of small-bowel perforation secondary to Clostridium difficile enteritis
      are described and compared with the 8 cases of C difficile enteritis reported in
      the medical literature. The cause of small-bowel involvement with C difficile is
      unknown, but prior antibiotic use, prior colectomy, chronic alterations in small
      bowel flora, and other host factors are discussed.

PMID- 16415420
TI  - Image of the month: acute and chronic cholecystitis with abscess formation.

PMID- 16415421
TI  - No nonagenarians please!

PMID- 16415422
TI  - Venous bicarbonate correlates linearly with arterial base deficit only if pH is
      constant.

PMID- 16415423
TI  - The role of positron emission tomography and computed tomography fusion in the
      management of early-stage and advanced-stage primary head and neck squamous cell
      carcinoma.
AB  - OBJECTIVE: To evaluate the role of positron emission tomography and computed
      tomography (PET-CT) fusion in the management of early-stage and advanced-stage
      primary head and neck squamous cell cancer. DESIGN: Retrospective analysis, with
      a blinded evaluation of clinical data and formation of a treatment plan. SETTING:
      Single tertiary academic medical institution. Patients Thirty-six patients with
      previously untreated head and neck squamous cell carcinoma who underwent staging
      CT or magnetic resonance imaging of the neck prior to undergoing PET-CT as part
      of their initial diagnostic evaluation between July 2000 and January 2005. MAIN
      OUTCOME MEASURES: Confirmation or alteration of the treatment plan with the
      addition of the PET-CT information compared with traditional clinical and
      radiological data alone for early-stage and advanced-stage disease. When
      available, histopathological results were correlated with the PET-CT findings.
      RESULTS: Among the 36 patients, PET-CT provided additional information that
      confirmed the treatment plan in 25 patients (69%) and altered the treatment plan
      in 11 patients (31%). Six of 11 patients in the altered-treatment group had their
      tumors upstaged. Four of 8 patients with early-stage tumors had their treatment
      plan altered, compared with 7 of 28 patients with advanced-stage disease. Among
      18 patients who underwent a surgical intervention for their primary tumor, PET-CT
      identified the primary tumor in all 18 patients and, based on histopathological
      findings, correctly staged the regional nodal disease in 9 of 16 patients who had
      their nodal disease addressed. CONCLUSION: The use of PET-CT is important in the
      initial treatment planning of early-stage and advanced-stage head and neck
      squamous cell carcinoma.

PMID- 16415424
TI  - Hyaluronan-CD44 promotes phospholipase C-mediated Ca2+ signaling and cisplatin
      resistance in head and neck cancer.
AB  - OBJECTIVE: To investigate whether hyaluronan (HA)-CD44 promotes head and neck
      squamous cell carcinoma (HNSCC) cisplatin resistance and whether HA-CD44 promotes
      phospholipase C (PLC)-mediated Ca2+ signaling to alter cisplatin sensitivity in
      HNSCC. DESIGN: Cell line study. MAIN OUTCOME MEASURES: Tumor cell growth with the
      chemotherapeutic drug cisplatin was measured in the presence or absence of HA,
      anti-CD44 antibody plus HA, and other inhibitors of the PLC-mediated Ca2+
      signaling pathway. Ca2+ mobilization was measured with fluorescence
      spectrophotometry using the Ca2+ binding dye Fura/2AM. RESULTS: In the absence of
      HA, cisplatin inhibited tumor cell growth. The addition of HA, but not HA plus
      anti-CD44 antibody, resulted in a 5-fold reduced ability of cisplatin to cause
      HNSCC cell death, suggesting that HA can promote CD44-dependent cisplatin
      resistance. Fluorescence spectrophotometry demonstrated that HA can promote CD44
      dependent Ca2+ mobilization in HNSCC. On the other hand, the presence of U73122,
      a PLC inhibitor, and 2-aminoethoxydiphenyl borate, an inositol-1,4,5-triphosphate
      receptor inhibitor, eliminated HA-mediated Ca2+ mobilization and HA-mediated
      cisplatin resistance in these cell lines. CONCLUSIONS: Our results indicate that
      HA-CD44 signaling influences cisplatin sensitivity in HNSCC cell growth. In
      particular, HA-CD44 promotion of PLC-mediated Ca2+ signaling plays a role in
      cisplatin resistance in HNSCC cells. Perturbation of this HA-CD44-mediated
      signaling pathway may be a promising target to overcome cisplatin resistance in
      HNSCC.

PMID- 16415426
TI  - Socioeconomic effects of and risk factors for disability in long-term survivors
      of head and neck cancer.
AB  - OBJECTIVE: To evaluate the socioeconomic effect of and risk factors for work
      related disability due to head and neck cancer and its treatment. DESIGN: Cross
      sectional analysis of a consecutive series of patients. SETTING: Tertiary cancer
      center hospital. PATIENTS: Eligible patients had squamous cell carcinoma of the
      upper aerodigestive tract, were employed or had an active professional career at
      the time of initial diagnosis, and were disease free for at least 2 years at the
      time of interview. The survey instruments were a specific questionnaire to
      evaluate patient socioeconomic status and a Portuguese version of the University
      of Washington Quality of Life questionnaire. MAIN OUTCOME MEASURES: Descriptive
      analysis of the results and associations between clinical, social, and quality of
      life variables with work disability. RESULTS: A total of 301 patients were
      studied. There were 236 (78.4%) men (median age, 52 years). The tumor sites were
      the oral cavity in 158 (52.5%), oropharynx in 55 (18.3%), larynx in 78 (25.9%),
      and hypopharynx in 10 (3.3%). Most patients presented with advanced clinical
      disease and underwent surgical treatment initially. There were 36 (12.0%)
      illiterate patients, and only 23 (7.6%) patients had completed college. Ninety
      nine patients (32.9%) became unable to work, and 126 (41.9%) reported a
      significant decrease in household income. Multivariate analysis showed that
      advanced clinical stage (P = .02), alcohol consumption (P = .02), and low
      educational level (P = .007) were associated independently with work disability.
      CONCLUSIONS: We observed a high rate of work-related disability that led to
      significant decrease in household income. Several clinical, social, and quality
      of life variables were associated with this degree of disability. These results
      could be used to better define who should undergo more intensive rehabilitation
      aiming to reduce work disability. If intensive rehabilitation is unsuccessful,
      these patients should receive more comprehensive social support.

PMID- 16415425
TI  - Does quality of life predict long-term survival in patients with head and neck
      cancer?
AB  - OBJECTIVE: To assess whether pretreatment and posttreatment quality of life (QOL)
      is associated with long-term survival in patients with head and neck cancer.
      DESIGN: Ten-year follow-up of an inception cohort. SETTING: Regional tertiary
      referral center. PATIENTS: The study included 200 consecutive patients with
      primary epithelial head and neck cancer. INTERVENTIONS: Quality of life and
      several recognized risk factors for death were assessed prospectively using the
      Auckland QOL questionnaire before treatment and 12 months after treatment;
      survival was determined at 10 years. MAIN OUTCOME MEASURES: Survival and odds of
      death (hazards ratio) were measured. RESULTS: At 10 years, 136 patients (68%)
      were deceased, 48 patients (24%) were alive, and the status of 16 patients (8%)
      was unknown. Median survival was 6 years (interquartile range, 4.4-7.7). Before
      treatment, patients with low QOL had no significantly increased odds of death
      (hazard ratio, 1.4; 95% confidence interval, 0.8-2.4). In contrast, after
      treatment, patients with low QOL at 1 year had significantly increased odds of
      death (2.5; 95% confidence interval, 1.4-4.3; P = .001) even after adjustment for
      covariates. CONCLUSIONS: Findings suggest potential survival benefits from
      improvements in QOL. However, the observed associations between survival benefit
      and QOL at 1 year may be confounded by comorbidity, which was not measured and
      deserves further investigation.

PMID- 16415427
TI  - Risk factors for the development of hypothyroidism after hemithyroidectomy.
AB  - OBJECTIVES: To assess the incidence of hypothyroidism after hemithyroidectomy and
      to identify risk factors for the development of hypothyroidism. DESIGN:
      Retrospective analysis. SETTING: A tertiary care academic medical center.
      PATIENTS: The study included 90 patients who underwent a hemithyroidectomy from
      1999 to 2004. MAIN OUTCOME MEASURES: Hypothyroidism was defined as a serum
      thyrotropin level greater than 6.0 mIU/L at least 8 weeks after
      hemithyroidectomy. All patients were analyzed for age, sex, surgical indications,
      preoperative and postoperative thyrotropin levels, weight of resected specimen,
      final pathologic analysis, and length of follow-up. Multivariate analysis was
      performed to identify multiple risk factors for the development of
      hypothyroidism. RESULTS: The final pathologic analysis demonstrated 49 follicular
      adenomas, 17 cases of Hashimoto thyroiditis, 10 multinodular goiters, and 14
      other abnormalities. The overall incidence of the development of hypothyroidism
      after hemithyroidectomy was 27% (24 of 90 patients). When the groups were broken
      down by pathologic diagnosis, the incidence of hypothyroidism developing during
      follow-up among the Hashimoto thyroiditis and multinodular goiter groups was 59%
      and 50%, respectively. Also, the patients who developed hypothyroidism were noted
      to have statistically significant higher preoperative serum thyrotropin levels
      (3.15 mIU/L vs 1.95 mIU/L; P<.001) than those who remained euthyroid. There was
      no relationship between age, sex, or weight of the resected tissue and the
      subsequent risk of hypothyroidism. CONCLUSIONS: The overall incidence of
      posthemithyroidectomy hypothyroidism was 27%, and the majority of cases developed
      in the first 6 to 12 months after surgery. Risk factors for the development of
      hypothyroidism include pathologic diagnosis (Hashimoto thyroiditis and
      multinodular goiter) as well as a high-normal serum thyrotropin level. Routine
      monitoring of serum thyrotropin levels should be performed in all patients who
      undergo a hemithyroidectomy.

PMID- 16415428
TI  - Prospective study of perioperative factors predicting hypocalcemia after thyroid
      and parathyroid surgery.
AB  - OBJECTIVE: To identify whether perioperative 1,25-dihydroxyvitamin D or
      parathyroid hormone (PTH) levels will predict the development of hypocalcemia
      after thyroid and parathyroid surgery. DESIGN: Prospective study. SETTING:
      University hospital. PATIENTS: The study included 103 patients who underwent
      thyroid or parathyroid surgery between 2002 and 2004, with a comparison of the
      patients who underwent thyroid lobectomy (TL; n = 34), total thyroidectomy (TT; n
      = 27), parathyroid adenoma excision (PAE; n = 34), and subtotal parathyroidectomy
      for hyperplasia (SP; n = 8). MAIN OUTCOME MEASURES: Preoperative 1,25
      dihydroxyvitamin D levels, number of patients requiring calcium replacement, and
      postoperative PTH and calcium levels. RESULTS: No patients in the TL or PAE group
      developed postoperative hypocalcemia that required calcium replacement. Six
      patients (22%) in the TT group and 3 patients (38%) in the SP group required
      calcium replacement for clinically significant hypocalcemia (P<.001). All
      patients who required calcium replacement had PTH levels of less than 15 pg/mL
      (1.6 pmol/L) 8 hours after surgery. Among the patients with postoperative PTH
      levels of less than 15 pg/mL (1.6 pmol/L) 8 hours after surgery, no patients in
      the PAE group required calcium replacement, compared with 75% of patients in the
      TT and SP groups (P<.001). The patients in the TT group had significantly lower
      postoperative calcium levels than those in the TL (P<.001) or the PAE (P<.005)
      group. The patients in the TL group reached stable calcium levels significantly
      earlier than those in the other groups (15.8 hours after surgery; P<.05). There
      was no relationship between preoperative 1,25-dihydroxyvitamin D levels and
      postoperative calcium levels. CONCLUSIONS: Preoperative 1,25-dihydroxyvitamin D
      levels were not predictive of postoperative calcium levels. Patients who undergo
      PAE or TL are at extremely low risk for requiring calcium replacement. Patients
      who undergo TT or SP with 8-hour postoperative PTH levels greater than or equal
      to 15 pg/mL (1.6 pmol/L) are at low risk for developing postoperative
      hypocalcemia, whereas those with PTH levels less than 15 pg/mL (1.6 pmol/L) have
      a high risk of developing hypocalcemia.

PMID- 16415429
TI  - The cost-effectiveness of additional preoperative ultrasonography or sestamibi
      SPECT in patients with primary hyperparathyroidism and negative findings on
      sestamibi scans.
AB  - OBJECTIVE: To determine whether the use of additional preoperative imaging was
      cost-effective compared with bilateral neck exploration (BNE) for the treatment
      of primary hyperparathyroidism in patients with negative findings on scans with
      technetium Tc 99m sestamibi. DESIGN: We performed a cost-effectiveness analysis.
      The decision whether to proceed to BNE or obtain additional preoperative imaging
      using ultrasonography (US) or single-photon emission computed tomography with
      technetium Tc 99m sestamibi (SPECT) was modeled using decision analysis. We
      obtained probabilities of cure, detection of pathologic glands, and the correct
      side of the neck from recent literature. MAIN OUTCOME MEASURES: Expected cost,
      cure rate, and the incremental cost per cured case using the preoperative imaging
      strategies compared with BNE. RESULTS: The US strategy dominated the SPECT and
      BNE strategies, with a lower expected cost (USD $6030 vs USD $7131 and $8384,
      respectively) and a greater expected cure rate (99.42% vs 99.26% and 97.69%,
      respectively). Threshold analysis suggests that the preoperative imaging
      strategies continued to dominate unless the cost of BNE was less than USD $5400
      or the cost of unilateral neck exploration exceeded USD $6500. The US strategy
      dominated SPECT as a preoperative imaging strategy if the cost of SPECT exceeded
      $12 or the cost of a US test was less than $1300. CONCLUSIONS: For the treatment
      of primary hyerparathyroidism in the patient with negative findings on technetium
      Tc 99m sestamibi scans, a strategy that uses additional preoperative US imaging
      appears to be cost-effective compared with SPECT or BNE.

PMID- 16415430
TI  - Hurthle cell tumors: applying molecular markers to define a new management
      algorithm.
AB  - OBJECTIVE: To design a new management algorithm for all Hurthle cell tumors and
      variants based on histopathologic findings and the ret/PTC molecular marker.
      DESIGN: A retrospective medical record review. SETTING: A large tertiary care
      teaching center. PATIENTS: Forty-five consecutive cases of Hurthle cell carcinoma
      were gathered from a database of 661 patients with well-differentiated epithelial
      thyroid cancers compiled over 22 years. Data collected included patient
      information, tumor information, and treatment factors. MAIN OUTCOME MEASURES:
      Outcome parameters included tumor and treatment variables, which were analyzed
      statistically using the chi(2) and t tests. Disease-free survival and disease
      specific survival analyses were performed using Kaplan-Meier analysis. RESULTS: A
      female-male ratio of 3:1 was found, with a median patient age of 57 years. Twenty
      three patients had American Joint Commission on Cancer stage II disease.
      Treatment factors had no significant effect on disease recurrence or survival.
      More than half of the patients had histologically proved regional metastases.
      Vascular invasion significantly diminished disease-specific survival and disease
      free interval. CONCLUSIONS: We found a high incidence of Hurthle cell carcinoma
      with cervical metastasis. On the basis of findings of this study and our previous
      clinical and molecular findings, we propose a treatment algorithm that combines
      histologic examination and molecular assays for the ret/PTC gene rearrangements
      specific to papillary thyroid carcinoma. After permanent section analysis
      demonstrating Hurthle cell metaplasia, the algorithm mandates completion
      thyroidectomy in patients with ret/PTC-positive Hurthle cell tumors and clinical
      observation for ret/PTC-negative Hurthle cell adenomas. We recommend more
      aggressive treatment of ret/PTC-positive Hurthle cell lesions (or Hurthle cell
      papillary thyroid cancer), because of the higher incidence of regional metastatic
      disease.

PMID- 16415432
TI  - Complications in head and neck surgery: a meta-analysis of postlaryngectomy
      pharyngocutaneous fistula.
AB  - OBJECTIVE: To summarize the potential risk factors for postlaryngectomy
      pharyngocutaneous fistula. DATA SOURCES: Observational studies in the English
      language literature about postlaryngectomy pharyngocutaneous fistula from January
      1, 1970, to March 31, 2003. Studies were identified through a MEDLINE search with
      relevant key words; additional studies were identified through references. STUDY
      SELECTION: We included studies about the site of primary malignancy, type of
      procedure, and type of closure; studies had to have been based on individual
      level data, with a comparison group for each risk factor evaluated. DATA
      EXTRACTION: Data required to calculate the relative risk of fistula associated
      with commonly reported risk factors were abstracted from the studies, and a meta
      analysis using a random-effects approach was performed to estimate a summary
      relative risk of fistula for each risk factor. The statistical significance of
      heterogeneity of effects among studies was assessed. DATA SYNTHESIS: Of 65
      studies identified, 26 met the inclusion criteria. Significant risk factors
      identified in the pooled analysis included postoperative hemoglobin level less
      than 12.5 g/dL, prior tracheotomy, preoperative radiotherapy, and preoperative
      radiotherapy and concurrent neck dissection. The degree of heterogeneity of
      effects among studies was significant for postoperative hemoglobin level,
      preoperative radiotherapy, concurrent neck dissection, and comorbid illness. The
      severity of fistula was greater in patients with a history of radiotherapy.
      CONCLUSIONS: This meta-analysis identified several significant risk factors for
      postlaryngectomy pharyngocutaneous fistula. The clinical implications of these
      findings and the potential sources of heterogeneity of effects among studies are
      discussed.

PMID- 16415431
TI  - Results of surgical salvage after failure of definitive radiation therapy for
      early-stage squamous cell carcinoma of the glottic larynx.
AB  - OBJECTIVE: To report the outcome of surgical salvage performed for early-stage
      squamous cell carcinoma of the glottic larynx that recurred or progressed after
      definitive radiotherapy. DESIGN: Retrospective outcome analysis. SETTING:
      Tertiary referral center specializing in head and neck cancer. PATIENTS: Forty
      three patients who underwent salvage surgery after definitive radiation therapy
      for early-stage (T1-T2) glottic cancer were identified from a preexisting
      database of 662 patients with squamous cell carcinoma of the larynx treated at
      Memorial Sloan-Kettering Cancer Center between the years 1984 and 1998. The T
      stage at initial presentation was T1 in 20 (18%) and T2 in 23 (32%). Twenty-one
      patients (49%) were amenable to salvage partial laryngectomy (SPL), but 22 (51%)
      required salvage total laryngectomy (STL). Details on patient characteristics,
      tumor characteristics, postoperative complications, and survival outcome were
      extracted from the database. MAIN OUTCOME MEASURES: Overall survival, disease
      specific survival, neck recurrence-free survival, and distant recurrence-free
      survival. RESULTS: No postoperative death occurred following salvage surgery. The
      overall incidence of complications was 21%, with no difference between the SPL
      and STL groups. Patients who required STL had poorer overall survival and disease
      specific survival compared with patients who required SPL (overall survival, 50%
      vs 89%; P = .003; disease-specific survival, 51% vs 93%; P = .002). This
      difference in survival was associated with a poorer neck recurrence-free survival
      and distant recurrence-free survival in the STL group compared with the SPL group
      (neck recurrence-free survival, 80% vs 100%; P = .04; distant recurrence-free
      survival, 71% vs 93%; P = .06). Univariate analysis showed that age and clinical
      T stage at recurrence were predictors of overall survival, disease-specific
      survival, and distant recurrence-free survival. CONCLUSIONS: Careful selection of
      patients with early-stage glottic tumors that recur or progress after radiation
      allows patients to be successfully treated by partial laryngectomy with excellent
      survival outcome. However, despite an aggressive policy of performing partial
      laryngectomy when feasible, up to 50% of patients will require a total
      laryngectomy owing to progression of disease. These patients have poorer survival
      outcomes manifested by local, regional, and distant disease progression.

PMID- 16415433
TI  - Craniofacial resection for malignant melanoma of the skull base: report of an
      international collaborative study.
AB  - OBJECTIVE: To report postoperative mortality, complications, and outcomes in a
      subset of patients with the histologic diagnosis of malignant melanoma extracted
      from an existing database of a large cohort of patients accumulated from multiple
      institutions. DESIGN: Retrospective outcome analysis. SETTING: Seventeen
      international tertiary referral centers performing craniofacial surgery for
      malignant skull base tumors. PATIENTS: A total of 53 patients were identified
      from a database of 1307 patients who had craniofacial resection for malignant
      tumors at 17 institutions. The median age was 63 years. Of the 53 patients, 25
      (47%) had had prior single modality or combined treatment, which included surgery
      in 22 (42%), radiation in 11 (21%), and chemotherapy in 2 (4%). The margins of
      resection were close or microscopically positive in 7 (13%). Adjuvant
      radiotherapy was given in 22 (42%), chemotherapy in 3 (6%), and vaccine or
      interferon therapy in 2 (4%). Complications were classified into overall, local,
      central nervous system, systemic, and orbital. Overall survival (OS), disease
      specific survival (DSS), and recurrence-free survival (RFS) were determined using
      the Kaplan-Meier method. Predictors of outcome were identified by multivariate
      analysis. RESULTS: Postoperative mortality occurred in 3 patients (6%) and
      postoperative complications were reported in 14 patients (26%). Local wound
      complications occurred in 6 patients (11%), central nervous system in 7 (13%),
      systemic in 3 (6%), and orbital in 1 (2%). With a median follow-up of 10 months
      (range, 1-159 months), the 3-year OS, DSS, and RFS rates were 28.2%, 29.7%, and
      25.5%, respectively. The extent of orbital involvement and adjuvant postoperative
      radiation therapy (PORT) were independent predictors of DSS and OS on
      multivariate analysis, whereas only PORT was an independent predictor of RFS.
      Patients treated with PORT had significantly better 3-year OS (39% vs 18%;
      relative risk, 2.9; P = .007), DSS (41% vs 19%; relative risk, 3.0; P = .007),
      and RFS (39% vs 15%; relative risk, 4.2; P = .001). CONCLUSIONS: Craniofacial
      resection in patients with malignant melanoma of the skull base has mortality
      (6%) and complication rates (26%) comparable to other malignant tumors of the
      skull base. However, malignant melanoma is associated with a much poorer OS, DSS,
      and RFS. Adjuvant PORT correlated with improved 3-year OS, DSS, and RFS on
      multivariate analysis. These factors must be taken into account when considering
      craniofacial resection in a patient with malignant melanoma invading the skull
      base.

PMID- 16415435
TI  - Familial nasopharyngeal carcinoma in a cohort of 200 patients.
AB  - OBJECTIVES: To describe the characteristics of familial nasopharyngeal carcinoma
      (NPC) in a high-risk population and to determine the role of screening first
      degree relations. DESIGN: An analysis on a cohort of 200 patients newly diagnosed
      as having NPC. SETTING: A tertiary-level institution. PATIENTS: The patients were
      divided into 2 groups. Patients in group 1 had a first-degree relative with NPC,
      and those in group 2 did not. For patients in group 1, the relationship and the
      time interval between affected relatives were noted. The clinical and
      pathological factors of the 2 groups were obtained and statistically analyzed.
      RESULTS: There were 15.5% of NPC patients who had an affected first-degree
      relative. Of the affected relatives, 71% were siblings and 29% were parents. The
      mean interval between affected siblings was 5.3 years, while that between an
      affected parent and a child was 24.5 years. No differences were noted in the
      clinical factors between familial and nonfamilial NPC patients. Most patients in
      both groups were diagnosed as having stage III or IV NPC. CONCLUSIONS: The rate
      of familial NPC in our study is 15.5%. Siblings are more commonly affected, and
      the interval between 2 affected siblings is relatively short. No distinct
      clinical pattern exists in familial NPC. We recommend that siblings of NPC
      patients be screened as soon as possible once the index case is diagnosed.

PMID- 16415434
TI  - Selective neck dissection for node-positive necks in patients with head and neck
      squamous cell carcinoma: a word of caution.
AB  - OBJECTIVE: To evaluate the regional recurrence (RR) rate in a consecutive series
      of patients with node-positive head and neck squamous cell carcinoma (N(+) HNSCC)
      who underwent selective neck dissection (SND) as part of their treatment in a
      single institution. DESIGN: Retrospective case series with 2 years of follow-up.
      SETTING: Tertiary care university hospital. PATIENTS: One hundred ninety-one
      patients with N(+) HNSCC underwent 256 neck dissections (NDs) between 1999 and
      2002. Of these, 17 had unilateral SNDs and 11 had bilateral NDs (6 patients,
      bilateral SND; 5 patients, radical ND and SND). There were 22 men and 6 women,
      ranging in age from 37 to 79 years (median age, 53 years), with 17 laryngeal, 5
      hypopharyngeal, 4 oral cavity, 1 oropharyngeal, and 1 nasopharyngeal primary
      tumors, which were classified as follows: T1 (n=2 [7.1%]), T2 (n=2 [7.1%]), T3
      (n=7 [25.0%]), and T4 (n=17 [60.8%]). The neck stages were N1 (n=8 [28.6%]), N2a
      (n=2 [7.1%]), N2b (n=7 [25.0%]), and N2c (n=11 [39.3%]). Most patients had tumors
      that were stage III (14.3%) or stage IV (85.7%) and had undergone postoperative
      radiotherapy. The minimum follow-up period was 2 years (median follow-up period,
      36 months). Two patients (7.1%) died of postoperative complications, and 2 became
      unavailable for follow-up before 12 months. MAIN OUTCOME MEASURE: The RR rate.
      RESULTS: There were 4 RRs (11.8%) among 34 patients who underwent SND, and 2 RRs
      (40%) among 5 patients who underwent radical ND. None of the patients with T1 or
      T2 tumors had recurrences; 1 (14.3%) of 7 patients with T3 tumors and 3 (17.6%)
      of 17 patients with T4 disease had RRs. One (12.5%) of 8 patients with N1 stage
      cancer, none of 2 patients with N2a stage cancer, 2 (28.6%) of 7 patients with
      N2b stage cancer, and 1 (9.1%) of 11 patients with N2c stage cancer had RRs.
      CONCLUSIONS: The RR rate was acceptable in patients with T1/T2 tumors and N1
      nodal stage disease. However, it was higher in those with advanced T tumors
      and/or N2b stage cancer.

PMID- 16415436
TI  - Aberrant internal carotid artery in the temporal bone: imaging findings and
      management.
AB  - OBJECTIVES: To describe the clinical and radiological features of the vascular
      anomaly aberrant internal carotid artery (ICA) in the temporal bone and to
      discuss management strategies. DESIGN: Retrospective study. PATIENTS: Sixteen
      cases of aberrant ICA were diagnosed between 1982 and 2003. RESULTS: Of 16 cases,
      11 were recognized by imaging assessment, 4 were recognized during middle ear
      surgery, and 1 was recognized clinically. Among the 11 cases, 8 malformations
      were diagnosed because of otologic symptoms related to the abnormal ICA or
      chronic otitis, while the other 3 were identified incidentally because of an
      underlying accompanying disease. In 4 cases, the diagnosis was made during
      surgery related to chronic otitis media (n = 2) or conductive hearing loss (n =
      2). In these 4 cases, massive bleeding resulted from surgical injury to the
      vessel. Packing the external auditory canal and the middle ear first controlled
      the bleeding. Endovascular procedure was required in 2 cases to exclude an
      aneurysm or to control bleeding but was followed by anterior cerebral stroke in 1
      case. The aberrant ICA could be identified on computed tomographic scan by the
      following features: intratympanic mass, enlarged inferior tympanic canaliculus,
      absence of the vertical segment of the ICA canal, and absence of bone covering
      the tympanic portion of the ICA. Conventional angiography was mandatory when
      intervention was planned to control bleeding or aneurysm. CONCLUSIONS: This study
      highlights that aberrant ICA has to be identified before any middle ear surgery
      because misdiagnosis may lead to dramatic surgical complications, whereas
      diagnosis with computed tomographic scan is easy. Bleeding is a minor
      complication compared with the putative neurologic deficit due to endovascular
      occlusion.

PMID- 16415437
TI  - Lymphocytopenia in children with lymphatic malformation.
AB  - OBJECTIVE: To determine whether an immunologic abnormality exists in patients
      with lymphatic malformation (LM). DESIGN: Retrospective case series. SETTING:
      Tertiary care pediatric hospital. PATIENTS: Twenty-one consecutive patients (11
      male and 10 female) undergoing LM treatment. INTERVENTIONS: Clinical data (ie,
      age, clinical LM stage, radiographic appearance, and histologic findings) were
      correlated with complete blood cell count and detailed lymphocyte differential.
      Complete blood cell counts and lymphocyte subsets were measured in 21 and 18
      patients, respectively. RESULTS: The average age at the time of testing was 67
      months (range, 1-231 months). The patients were categorized according to LM
      stage, including 4 (19%) with stage 1, 4 (19%) with stage 2, 4 (19%) with stage
      3, 7 (33%) with stage 4, and 2 (10%) with stage 5 disease. Radiographic LM
      appearance was macrocystic in 6 patients (29%), mixed macrocystic and microcystic
      in 8 (38%), and microcystic in 7 (33%). Complete blood cell count data
      demonstrated lymphocytopenia in 6 patients (29%). The results of the lymphocyte
      subset tests showed concomitant T-, B-, and natural killer (NK)-cell deficiency
      in 6 (33%) of 18 patients. All 6 patients with T-cell lymphocytopenia had normal
      neutrophil and platelet counts. Spearman rank and chi(2) analyses showed that LM
      stage 4 or 5 and microcystic LM were significantly associated with
      lymphocytopenia (P = .002 and P = .008, respectively). Histologic analysis did
      not demonstrate increased lymphocytes in any LM specimens. CONCLUSION: We found
      T, B, and NK lymphocytopenia in patients with large bilateral or microcystic LM.
      Although the relationship between lymphocytopenia and infection was not addressed
      in this study, the recognition of lymphocytopenia in patients with LM may have
      important clinical and prognostic implications.

PMID- 16415438
TI  - A glottic wood chip presenting as chronic dysphonia: report of a case and review
      of the literature.

PMID- 16415439
TI  - Radiology quiz case 1: Intracranial schwannoma originating from the greater
      petrosal nerve.

PMID- 16415440
TI  - Radiology quiz case 2: Cystic schwannoma of the lingual nerve.

PMID- 16415441
TI  - Pathology quiz case: Metastatic osteosarcoma of the external auditory canal.

PMID- 16415442
TI  - Negative-pressure pulmonary edema after routine septorhinoplasty: discussion of
      pathophysiology, treatment, and prevention.
AB  - OBJECTIVE: To provide rhinologic surgeons with an understanding of acute negative
      pressure pulmonary edema (NPPE) and its treatment. DESIGN: Case report and
      literature review of all published adult cases of NPPE. Patient factors,
      anesthetic variables, and outcomes are assessed. RESULTS: A total of 146 cases in
      45 case reports and series were compiled. There was approximately a 2:1 male
      female patient ratio. The average age of the patients was 33 years. Fifty percent
      of patients had surgery on the upper aerodigestive tract, and 8% had intranasal
      surgery. No patients received laryngotracheal anesthesia, and 5 of the 146
      received intravenous lidocaine prior to extubation. One patient had NPPE
      following laryngeal mask airway treatment, and 2 patients experienced this
      complication after conversion from monitored anesthesia care to general
      endotracheal anesthesia; 33.5% of patients were treated with continuous positive
      airway pressure alone, while 66.5% required intubation and mechanical
      ventilation. The average time to resolution was 11.75 hours. Three patients died.
      CONCLUSIONS: It is known that surgical procedures involving the upper
      aerodigestive tract have a higher risk of NPPE than other procedures. Rapid
      diagnosis and treatment is necessary to achieve early resolution and avoid
      significant patient morbidity. A thorough understanding is integral to the
      practice of nasal and paranasal sinus surgery, especially with the rising use of
      outpatient and office-based surgical suites. Therefore, we present a review of
      pathophysiologic mechanisms, possible risk factors, treatment options, and
      potential steps that can be taken to minimize this potentially devastating
      complication of general anesthesia.

PMID- 16415443
TI  - The M-Arch model: a new concept of nasal tip dynamics.
AB  - The M-Arch Model introduced herein expands on the utility and simplicity of the
      tripod concept to consider the overall length of the cartilaginous tripod arch as
      the major determinant of nasal tip parameters. Surgeons may exploit this powerful
      tool using modern grafting, suture, and cartilage-cutting techniques to
      predictably achieve desired tip alterations and, by extension, more consistently
      satisfactory aesthetic outcomes.

PMID- 16415444
TI  - Quantitative assessment of nasal changes after maxillomandibular surgery using a
      3-dimensional digital imaging system.
AB  - OBJECTIVE: To evaluate nasal changes after maxillomandibular surgery by means of
      images taken with a 3-dimensional digital camera. DESIGN: Thirty-two patients (26
      female and 6 male) with preoperative and postoperative 3-dimensional photographs
      were studied. The patients underwent maxillary movement with impaction (upward
      rotation), maxillary movement with lengthening (downward rotation), or maxillary
      movement without rotation. With the 3-dimensional imaging software, preoperative
      and postoperative calculations were performed for interalar width, internostril
      width, nasal tip projection, and columellar length from the 3-dimensional digital
      images. The nasolabial angle was also measured. RESULTS: Postoperative interalar
      and internostril widening was significant (P<.05) for all 3 categories of
      maxillary movement. However, there was no statistically significant change in
      nasal tip projection and columellar length. Interestingly, movement of the
      maxilla with upward rotation did show a statistically significant decrease in the
      nasolabial angle. CONCLUSIONS: Changes to the nose clearly occur after
      orthognathic surgery. There was a statistically significant increase in
      postoperative interalar width and internostril width with maxillary movement.
      However, no clear correlation could be determined between amount of change and
      maxillary movement. Interestingly, maxillary advancement did not show any
      significant change in nasal tip projection or columellar length, with data
      showing both increases and decreases in measurements. The nasolabial angle in
      patients who underwent maxillary advancement with impaction (upward rotation) was
      the only measurement that showed a statistically significant increase.

PMID- 16415445
TI  - Internal brow elevation at blepharoplasty.
AB  - OBJECTIVE: To present data on a transblepharoplasty technique that provides a
      safe and reliable brow elevation and glabellar furrow reduction by releasing
      inferior tethering and weakening the brow depressor muscles. DESIGN:
      Nonrandomized retrospective case series and surgical technique description.
      RESULTS: One thousand patients who underwent internal brow elevation for cosmesis
      associated with upper blepharoplasty over the past 9 years were reviewed. Follow
      up ranged from 6 months to 9 years. There were no serious long-term
      complications. All patients experienced forehead hypesthesia, which was temporary
      in most patients. Only 2 patients complained of prolonged and bothersome forehead
      hypesthesia lasting longer than 2 years. CONCLUSION: The internal brow elevation
      at blepharoplasty is a reproducibly safe and effective technique to improve
      eyebrow appearance without fixation.

PMID- 16415446
TI  - Concentric and eccentric carved costal cartilage: a comparison of warping.
AB  - OBJECTIVE: To determine if a systematic, concentric graft-carving technique
      results in less warping than eccentric carving. METHODS: Costal cartilage from
      ribs 3 through 9 were harvested from fresh human cadavers. Concentric dorsal
      grafts were carved from cartilage obtained from one side of the cadaver (n = 7)
      and eccentric grafts were carved from the opposite side (n = 11). After carving,
      grafts were placed in saline sponges (isotonic sodium chloride) for 1 hour, and
      photographs were then taken from a lateral and a frontal view. Identical
      photographs were taken after 2 weeks of incubation in saline (36.7 degrees C).
      The angle of curvature was measured from the photographs. RESULTS: More warping
      occurred in the eccentric group than the concentric group on lateral view at 1
      hour (4.4 degrees vs 0.4 degrees; P<.001) and at 2 weeks (5.8 degrees vs 1.4
      degrees; P = .003). Eccentric grafts progressively warped between the 1-hour and
      2-week points. CONCLUSION: Meticulous concentric carving of costal cartilage
      grafts may minimize the complication of graft warping.

PMID- 16415447
TI  - Duration of anesthesia as an indicator of morbidity and mortality in office-based
      facial plastic surgery: a review of 1200 consecutive cases.
AB  - OBJECTIVE: To define whether duration of anesthesia is an indicator of patient
      morbidity and mortality in facial plastic surgery performed in an accredited
      office-based surgical facility. DESIGN: A prospective and retrospective outcomes
      analysis of 1200 consecutive patients who underwent facial plastic surgery from
      July 1995 to February 2005. Outcomes of patients who underwent surgery with
      anesthesia for less than 240 minutes were compared with those of patients who
      underwent surgery with anesthesia for more than 240 minutes. RESULTS: Of the 1200
      cases analyzed, in 1032 (86%), duration of anesthesia was longer than 240
      minutes. There were no deaths and no cases of myocardial infarction or pulmonary
      embolism in this study group. Morbidity in the 1200 cases was reported as
      follows: 1 case of respiratory failure, 1 case of central nervous system deficit,
      1 case of adverse reaction to medication, and 1 case that required transfer to a
      hospital. There were 6 cases of prolonged recovery from anesthesia. Incidences of
      major morbidity in the group of 168 patients (14%) whose anesthesia lasted less
      than 240 minutes were the same as in the group whose anesthesia lasted more than
      240 minutes. CONCLUSIONS: In an accredited office-based facial plastic surgery
      facility, anesthesia duration is not an indicator of patient morbidity and
      mortality. Combined facial plastic surgery procedures, using general anesthesia,
      can be accomplished safely in the office-based environment, and inpatient care
      would not have altered morbidity in this study group.

PMID- 16415448
TI  - Effect of homeopathic Arnica montana on bruising in face-lifts: results of a
      randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVES: To design a model for performing reproducible, objective analyses of
      skin color changes and to apply this model to evaluate the efficacy of
      homeopathic Arnica montana as an antiecchymotic agent when taken perioperatively.
      METHODS: Twenty-nine patients undergoing rhytidectomy at a tertiary care center
      were treated perioperatively with either homeopathic A. montana or placebo in a
      double-blind fashion. Postoperative photographs were analyzed using a novel
      computer model for color changes, and subjective assessments of postoperative
      ecchymosis were obtained. RESULTS: No subjective differences were noted between
      the treatment group and the control group, either by the patients or by the
      professional staff. No objective difference in the degree of color change was
      found. Patients receiving homeopathic A. montana were found to have a smaller
      area of ecchymosis on postoperative days 1, 5, 7, and 10. These differences were
      statistically significant (P<.05) only on postoperative days 1 (P<.005) and 7
      (P<.001). CONCLUSIONS: This computer model provides an efficient, objective, and
      reproducible means with which to assess perioperative color changes, both in
      terms of area and degree. Patients taking perioperative homeopathic A. montana
      exhibited less ecchymosis, and that difference was statistically significant
      (P<.05) on 2 of the 4 postoperative data points evaluated.

PMID- 16415449
TI  - Mandibular lengthening in micrognathic infants with the internal distraction
      device.

PMID- 16415450
TI  - Management of the overprojected nasal tip.

PMID- 16415451
TI  - A prospective examination of the efficacy of 2 noninvasive devices for treatment
      of the aging face.

PMID- 16415453
TI  - Election promises: moving beyond health care.

PMID- 16415454
TI  - HTLV-1 virus detected in Nunavut.

PMID- 16415456
TI  - The evolving TNM cancer staging system: an essential component of cancer care.

PMID- 16415457
TI  - Prevalence of class I, II and III obesity in Canada.

PMID- 16415458
TI  - Headache and failure to thrive.

PMID- 16415459
TI  - Taking away the sting of malaria.

PMID- 16415460
TI  - An elderly man with fever and hypodense lesions in the spleen and liver.

PMID- 16415461
TI  - Dose-response relation between sulfonylurea drugs and mortality in type 2
      diabetes mellitus: a population-based cohort study.
AB  - BACKGROUND: Over the past 30 years, the relation between use of sulfonylureas to
      treat type 2 diabetes and the risk of cardiovascular events has been vigorously
      debated. The purpose of this study was to determine if the risk of death changes
      with level of exposure to sulfonylurea drugs. METHODS: This was a retrospective,
      inception cohort study using administrative data from Saskatchewan Health (1991
      1999). The 5795 subjects, identified by their first-ever dispensation for an oral
      antidiabetic agent, were grouped according to their use of such agents during
      follow-up. Potential subjects using insulin or combination therapy were excluded.
      Exposure level was defined by daily dose and degree of adherence. Separate
      multivariate Cox proportional-hazard models were constructed for each monotherapy
      group and used to calculate the risk of death associated with higher versus lower
      exposure category. Disease severity indicators were identified among the
      administrative data and entered as covariates in each model. The main outcomes
      were all-cause mortality and death from an acute ischemic event. RESULTS: The
      mean age of the cohort members was 66.3 (standard deviation [SD] 13.4) years;
      43.4% were female; and their mean duration of follow-up was 4.6 (SD 2.1) years.
      First-generation sulfonylureas were used exclusively by 120 subjects; glyburide,
      by 4138; and metformin, by 1537. A greater risk of death was associated with
      higher daily doses of the first-generation sulfonylureas (adjusted hazard ratio
      [HR] 2.1, 95% confidence interval [CI] 1.0-4.7) and glyburide (HR 1.3, 95% CI 1.2
      1.4), but not metformin (HR 0.8, 95% CI 0.7-1.1). Similar associations were
      observed for death caused by an acute ischemic event. INTERPRETATION: Higher
      exposure to sulfonylureas was associated with increased mortality among patients
      newly treated for type 2 diabetes. The same relation was not observed with
      metformin. This implies that the manner in which blood glucose concentration is
      lowered may be as important as achieving recommended glucose targets.

PMID- 16415463
TI  - Do sulfonylurea drugs increase the risk of cardiac events?

PMID- 16415462
TI  - Inequalities in access to medical care by income in developed countries.
AB  - BACKGROUND: Most of the member countries of the Organization for Economic
      Cooperation and Development (OECD) aim to ensure equitable access to health care.
      This is often interpreted as requiring that care be available on the basis of
      need and not willingness or ability to pay. We sought to examine equity in
      physician utilization in 21 OECD countries for the year 2000. METHODS: Using data
      from national surveys or from the European Community Household Panel, we
      extracted the number of visits to a general practitioner or medical specialist
      over the previous 12 months. Visits were standardized for need differences using
      age, sex and reported health levels as proxies. We measured inequity in doctor
      utilization by income using concentration indices of the need-standardized use.
      RESULTS: We found inequity in physician utilization favouring patients who are
      better off in about half of the OECD countries studied. The degree of pro-rich
      inequity in doctor use is highest in the United States and Mexico, followed by
      Finland, Portugal and Sweden. In most countries, we found no evidence of inequity
      in the distribution of general practitioner visits across income groups, and
      where it does occur, it often indicates a pro-poor distribution. However, in all
      countries for which data are available, after controlling for need differences,
      people with higher incomes are significantly more likely to see a specialist than
      people with lower incomes and, in most countries, also more frequently. Pro-rich
      inequity is especially large in Portugal, Finland and Ireland. INTERPRETATION:
      Although in most OECD countries general practitioner care is distributed fairly
      equally and is often even pro-poor, the very pro-rich distribution of specialist
      care tends to make total doctor utilization somewhat pro-rich. This phenomenon
      appears to be universal, but it is reinforced when private insurance or private
      care options are offered.

PMID- 16415464
TI  - Income and equity of access to physician services.

PMID- 16415465
TI  - Is the current approach to reviewing new drugs condemning the victims of rare
      diseases to death? A call for a national orphan drug review policy.

PMID- 16415466
TI  - Is there still a role for spontaneous reporting of adverse drug reactions?

PMID- 16415468
TI  - Clarifying a misunderstanding on clinical trial registry.

PMID- 16415467
TI  - The use of antidepressants to treat depression in children and adolescents.
AB  - The dramatic increase over the past 10 years in the amount of available clinical
      research on the use of antidepressants to treat major depression in children and
      adolescents has substantially improved our knowledge of the safety and efficacy
      of these medications in the pediatric population. Many questions remain, however,
      that highlight the need to continue research in this patient population rather
      than relying on the extrapolation of data from trials involving adults. In this
      article, we review the current state of research into antidepressant therapy for
      major depression in children and adolescents. In addition, we discuss
      methodologic issues and clinical implications specific to the pediatric
      population.

PMID- 16415470
TI  - Sharpening the point.

PMID- 16415471
TI  - Reducing procedural pain.

PMID- 16415474
TI  - Getting a grip on waiting lists.

PMID- 16415476
TI  - Coupling of two pools of P2X7 receptors to distinct intracellular signaling
      pathways in rat submandibular gland.
AB  - The plasma membrane of cells from rat submandibular glands was isolated and
      extensively sonicated. The homogenate was centrifuged at high speed in a
      discontinuous sucrose gradient. Light fractions contained vesicles analogous to
      rafts: they were rich in cholesterol, they contained GM1 and caveolin-1, and P2X7
      receptors were detected in these fractions. The location of the P2X7 receptors in
      rafts was abolished when cellular cholesterol was removed by methyl-beta
      cyclodextrin (MCD). ATP activated neutral sphingomyelinase (N-SMase), which
      provoked a decrease of the cellular content of sphingomyelin and an increase of
      ceramide levels in these cells and in the rafts. Treatment with MCD and filipin
      (but not with alpha-cyclodextrin) abolished the increase of the intracellular
      concentration of calcium ([Ca2+]i) in response to epinephrine but not to ATP. MCD
      and filipin also inhibited the activation by ATP of phospholipase A2 (PLA2).
      Inhibition of N-SMase with glutathione or GW4869 prevented the activation of PLA2
      by P2X7 agonists without affecting [Ca2+]i levels. We conclude that P2X7
      receptors are present in both raft and nonraft compartments of plasma membranes;
      the receptors forming a nonselective cation channel are located in the nonraft
      fraction. P2X7 receptors in the rafts are coupled to the activation of N-SMase,
      which increases the content of ceramides in rafts. This may contribute to the
      activation of PLA2 in response to P2X7 receptor occupancy.

PMID- 16415477
TI  - Toward a new generation of therapeutics: artificial cell targeted delivery of
      live cells for therapy.
AB  - Scientific evidence in the prevention and treatment of various disorders is
      accumulating regarding probiotics. The health benefits supported by adequate
      clinical data include increased resistance to infectious disease, decreased
      duration of diarrhea, management of inflammatory bowel disease, reduction of
      serum cholesterol, prevention of allergy, modulation of cytokine gene expression,
      and suppression of carcinogen production. Recent ventures in metabolic
      engineering and heterologous protein expression have enhanced the enzymatic and
      immunomodulatory effects of probiotics and, with time, may allow more active
      intervention among critical care patients. In addition, a number of approaches
      are currently being explored, including the physical and chemical protection of
      cells, to increase probiotic viability and its health benefits. Traditional
      immobilization of probiotics in gel matrices, most notably calcium alginate and
      kappa-carrageenan, has frequently been employed, with noted improvements in
      viability during freezing and storage. Conflicting reports exist, however, on the
      protection offered by immobilization from harsh physiologic environments. An
      alternative approach, microencapsulation in "artificial cells," builds on
      immobilization technologies by combining enhanced mechanical stability of the
      capsule membrane with improved mass transport, increased cell loading, and
      greater control of parameters. This review summarizes the current clinical status
      of probiotics, examines the promises and challenges of current immobilization
      technologies, and presents the concept of artificial cells for effective delivery
      of therapeutic bacterial cells.

PMID- 16415478
TI  - Continuous biotreatment of copper-concentrated solutions by biosorption with
      Sargassum sp.
AB  - Seaweed Sargassum sp. biomass proved to be useful for the recovery of ionic
      copper from highly concentrated solutions simulating effluents from semiconductor
      production. In the case of solutions containing copper in the form of chloride,
      sulfate, and nitrate salts, the best pH for the recovery of copper was 4.5. It
      was observed that copper biosorption from copper nitrate solutions was higher
      than the recovery of copper from copper chloride or copper sulfate solutions. The
      continuous system used was constituted of four column reactors filled with the
      biomass of Sargassum sp. and showed high operational stability. The biomass of
      Sargassum sp. in the reactors was gradually saturated from the bottom to the top
      of each column reactor. The biomass of Sargassum sp. in the first column
      saturated first, followed by a gradual saturation of the remaining columns owing
      to preconcentration performed by the biomass in the first column. The biomass of
      Sargassum in the bioreactors completely biosorbed the ionic copper contained in
      63 L of copper sulfate solution, 72 L of copper chloride solution, and 72 L of
      copper nitrate solution, all the solutions containing copper at 500 mg/L.
      Effluents produced after biosorption presented copper concentrations < 0.5 mg/L.

PMID- 16415479
TI  - Contribution of cell-surface components to Cu2+ adsorption by Pseudomonas putida
      5-x.
AB  - The contribution of various cell-surface components to Cu2+ adsorption by a Gram
      negative bacterium, Pseudomonas putida 5-x, that was isolated from local
      electroplating effluent with a high capability to accumulate heavy metal ions was
      studied. The cell superficial layer had a negative effect on Cu2+ adsorption of
      the bacterial cells. Cu2+ adsorption capacity of the separated cell envelopes was
      fivefold more than that of the intact cells, owing to the liberation of more and
      more binding sites during the separation process. Some main components in the
      cell envelope, such as the peptidoglycan (PEG) layer, outer membrane, and inner
      membrane, provide the capability for Cu2+ adsorption. The content of the
      components in the cell envelope is in the order inner membrane > outer membrane >
      PEG layer, and their Cu2+ adsorption capacity was in the order PEG layer > outer
      membrane > inner membrane. The total contribution of the separated PEG layer
      material to Cu2+ adsorption by the cell envelope was no more than 15%, and the
      outer membrane and inner membrane contributed about 30-35% and 25-30%,
      respectively. The relatively high phospholipid content in the outer membrane may
      be the major reason for the higher adsorption capacity of the outer membrane to
      Cu2+ and, hence, such a high Cu2+ adsorption capacity of P. putida 5-x cell
      envelope.

PMID- 16415480
TI  - The future of coproducts from corn processing.
AB  - Increased demand for ethanol as a fuel additive has resulted in dramatic growth
      in ethanol production. Ethanol is produced from corn by either wet milling or dry
      grind processing. In wet milling, the corn kernel is fractionated into different
      components, resulting in several coproducts. Wet-milling plants are capital
      intensive because of equipment requirements; they produce large volumes of
      ethanol and are corporate owned. In dry-grind processing, the corn kernel is not
      fractionated and only one coproduct, distillers' dried grains with solubles
      (DDGS), is generated. Dry-grind plants require less equipment and capital than
      wet mills. They generate smaller volumes of ethanol, are producer owned, and add
      direct benefits to rural economies. Most of the increase in ethanol production
      during the past decade is attributed to growth in the dry-grind industry. The
      marketing of coproducts provides income to offset processing costs. For dry-grind
      plants, this is especially important, because only one coproduct is available.
      Several issues could affect DDGS marketing. The increasing volume of DDGS
      accompanying ethanol production could reduce market value; high phosphorous
      content could limit the use of DDGS, because of animal waste disposal issues.
      Water removal is a costly processing step and affects the economics of ethanol
      processing. Technologies to remove germ and fiber from DDGS could produce a new
      coproduct suitable for feeding to nonruminants; this would expand the markets for
      DDGS. Reducing phosphorus in DDGS would sustain markets for conventional DDGS.
      The development of more efficient methods of water removal would increase the
      efficiency of ethanol processing and reduce the costs of processing. New
      technologies could contribute to greater stability of dry-grind plants.

PMID- 16415481
TI  - Effect of copper and manganese ions on activities of laccase and peroxidases in
      three Pleurotus species grown on agricultural wastes.
AB  - Copper (Cu2+) and manganese (Mn2+) ions influenced laccase (Lac) and peroxidase
      production in Pleurotus eryngii, Pleurotus ostreatus, and Pleurotus pulmonarius.
      In P. eryngii, the optimum Cu2+ concentration for Lac production was 1 mM and for
      peroxidases 10 mM, and Mn2+ concentration of 5 mM led to peaks of Lac and
      peroxidase activity. In P. ostreatus HAI 493, the highest level of Lac activity
      was at Cu2+ concentrations of 1 and 10 mM and Mn2+ concentration of 1 mM,
      respectively. The absence of Cu2+ and Mn2+ caused the highest levels of
      peroxidase production. In P. ostreatus HAI 494, the highest level of Lac activity
      was at a Cu2+ concentration of 5 mM and at Mn2+ concentration of 1 mM,
      respectively. High levels of peroxidase activity were found in the medium without
      and with 1 mM Cu2+, and at 1 and 5 mM Mn2+, respectively. In P. pulmonarius, the
      highest Lac activity was found in the presence of 5 mM Cu2+ and 5 mM Mn2+,
      respectively. The absence of Cu2+ and Mn2+ as well as their presence at a
      concentration of 1 mM led to the peaks of peroxidase activities.

PMID- 16415482
TI  - Large and micro coronary vascular involvement in diabetes.
AB  - Diabetes, with hyperglycemia as its hallmark, is a major risk factor for ischemic
      heart disease. The role of coronary disease in the adverse prognosis of diabetes
      is controversial although the higher prevalence and extension of coronary
      atherosclerosis is well recognized. The paper reviews the available evidence of
      coronary involvement in diabetes with particular emphases on microcirculation.
      Several studies, mainly in type 2 diabetes, have documented a reduced coronary
      flow reserve even in absence of coronary obstructive disease and using different
      techniques. Microcirculatory dysfunction affects the left ventricle globally as
      well as regionally. However, neither the prevalence of such abnormality in the
      diabetic population nor its time course and its prognostic value have been
      investigated in specifically addressed studies. In fact, a relatively large
      number of studies on myocardial perfusion performed by single-photon myocardial
      scintigraphy in asymptomatic diabetics rather address the problem of the
      prevalence of silent ischemia and its prognostic value. In spite of such
      limitation it can be speculated from the few available studies with known
      coronary anatomy that the prevalence of exclusively regional disturbances of
      perfusion (scintigraphic defects) in absence of obstructive coronary disease is
      not marginal as it ranges from 11 to 63%. Extensive research is still required to
      define the pathogenesis and the actual clinical relevance of coronary
      microcirculatory dysfunction in diabetes.

PMID- 16415483
TI  - Treatment of dyslipidemia in patients with diabetes mellitus.
AB  - The article reviews the key aspects of pathophysiology of diabetic dyslipidemia,
      its treatment and associated risk of cardiovascular complications. It examines
      the difference in lipid metabolism between type 1 and type 2 diabetes mellitus.
      The diagnostic values of particular lipid abnormalities as risk predictors for
      cardiovascular events are analyzed. Guidelines on hypolipemic treatment in
      diabetes are summarized and commented on. Standard and newly introduced methods
      as well as new opportunities of hypolipemic treatment are presented.

PMID- 16415484
TI  - Type 2 diabetes mellitus: from genes to disease.
AB  - The development of type 2 diabetes (T2DM) is determined by two factors: genetics
      and environment. The genetic background of T2DM is undoubtedly heterogeneous.
      Most patients with T2DM exhibit two different defects: the impairment of insulin
      secretion and decreased insulin sensitivity. This means that there are at least
      two pathophysiological pathways and at least two groups of genes that may be
      involved in the pathogenesis of T2DM. As far as genetic background [corrected] of
      T2DM is concerned, the disease may be divided into two large groups: monogenic
      and polygenic forms. In this review, we present genes known to cause rare
      monogenic forms of diabetes with predominant insulin deficiency (MODY - maturity
      onset diabetes of the young, MIDD - maternally inherited diabetes with deafness)
      and uncommon syndromes of severe insulin resistance. We also describe some of the
      main approaches used to identify genes involved in the more common forms of T2D
      and the reasons for the lack of spectacular success in this field. Although major
      genes for T2DM still await to be discovered, we have probably established a "road
      map" that we should follow.

PMID- 16415485
TI  - Aspirin resistance.
AB  - Aspirin protects many though not all patients from acute cardiovascular events.
      It is generally accepted that such prophylactic effect depends mainly on the
      antithrombotic action involving inhibition of thromboxane A(2) production and
      platelet aggregation. In many patients aspirin failure to protect against
      cardiovascular event is obvious, as their symptoms simply cannot be controlled by
      the administration of a single drug. Others do not adhere properly to the
      treatment regimen. There is, however, a group of subjects, in which aspirin fails
      to inhibit platelet function (measured by various in vitro tests) and thromboxane
      A(2)(TxA(2)) formation (measured either in whole blood or as urinary TXA(2)
      metabolite excretion). There is evidence that such impairment of biochemical
      aspirin effect may be of importance in predicting future cardiovascular events.
      Several factors can influence antiplatelet effectiveness of aspirin; among them:
      hypercholesterolemia, increased expression of the isoform 2 of cyclooxygenase,
      genetic factors (polymorphisms of beta(3) integrin, and factor XIII A-subunit),
      use of other nonsteroidal anti-inflammatory use, and possibly others. Still,
      several questions remain unanswered. While biochemical aspirin resistance can
      predict major cardiovascular events we are still lacking a reliable test to
      predict such a risk in an individual patient. In addition, we do not know whether
      any alteration in therapy may improve clinical outcome in a subject identified as
      aspirin-resistant.

PMID- 16415486
TI  - Blood platelet abnormalities and pharmacological modulation of platelet
      reactivity in patients with diabetes mellitus.
AB  - The overall picture of platelet abnormalities in diabetes mellitus (DM),
      including altered adhesion and aggregation, is hypersensitivity of diabetic
      platelets to agonists. "Primed" diabetic platelets respond more frequently even
      to subthreshold stimuli, sooner become exhausted, consumed and finally
      hyposensitive, thus contributing to accelerated thrombopoiesis and release of
      'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid
      metabolism may lead to physicochemical changes in cell membrane dynamics, and
      consequently result in altered exposure of surface membrane receptors. These
      phenomena, together with increased fibrinogen binding, prostanoid metabolism,
      phosphoinositide turnover and calcium mobilization often present in diabetic
      patients, contribute to enhanced risk of small vessel occlusions and accelerated
      development of atherothrombotic disease of coronary, cerebral and other vessels
      in diabetes. The paper concentrates on the role of dynamic, physico-chemical
      properties of platelet membrane lipid bilayer, as a major determinant of platelet
      hypersensitivity in diabetic patients. As a pharmacological response to platelet
      hypersensitivity in DM, making a major contribution to enhanced risk of
      thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality
      in diabetic individuals, we have a variety of antiplatelet agents, and
      acetylsalicylic acid (ASA) is no doubt most commonly used worldwide. Everyday
      clinical practice shows that antiplatelet pharmacological approach may not always
      be efficient enough in people with diabetes. Although we are at the very
      beginning of complete understanding of so-called 'aspirin-resistance', several
      potential molecular mechanisms of this phenomenon in diabetes have been
      evidenced.

PMID- 16415487
TI  - Endothelial nitric oxide synthase (eNOS) in platelets: how is it regulated and
      what is it doing there?
AB  - Platelets express the endothelial form of the nitric oxide synthase (eNOS) and
      generate NO. However, in contrast to eNOS in endothelial cells, eNOS in platelets
      is largely Ca(2+)-independent and the activity is regulated by phosphorylation.
      Platelet-derived NO plays an important role in the regulation of platelet
      aggregation and secretion. Changes in the activity of platelet eNOS are
      responsible for the abnormal platelet activation encountered in different
      pathological situations (e.g. hypertension and diabetes). In this review, we will
      summarize the current knowledge of the role of platelet eNOS and the regulation
      of its activity as well as the fate of platelet-derived NO in physiological and
      pathological situations.

PMID- 16415488
TI  - The future of traditional nonsteroidal antiinflammatory drugs and cyclooxygenase
      2 inhibitors in the treatment of inflammation and pain.
AB  - Prostanoids act leading roles in a myriad of physiologic and pathologic processes
      because these autacoids participate in the amplification of biological responses
      induced by innumerable stimuli. The formation of prostanoids is operated by two
      synthases named cyclooxygenase(COX)-1 and COX-2. Traditional nonsteroidal
      antiinflammatory drugs (tNSAIDs) and COX-2 inhibitors (coxibs) give rise to
      antipyretic, analgesic, and antiinflammatory actions, through their reversible
      clogging of the COX channel of COX-2 - apart from aspirin which modifies
      irreversibly the catalytic activity of COX-2. tNSAIDs and COX-2 inhibitors
      resulted clinically equivalent for the relief of acute pain and symptoms of
      arthropathies but they failed to modify disease progression. Clinical evidence of
      the possible contribution of COX-1 in inflammation and pain in some occasion - as
      suggested by experimental and pharmacology studies - is orphan because none
      efficacy trial with COX inhibitors was designed to establish it. COX-2 inhibitors
      were developed with the aim to reduce the incidence of serious gastrointestinal
      (GI) adverse effects associated with the administration of tNSAIDs ensued as a
      consequence of the inhibition of cytoprotective COX-1-derived prostanoids.
      However, the reduced incidence of serious GI adverse effects compared to tNSAIDs
      demonstrated for 2 COX-2 inhibitors (e.g. rofecoxib and lumiracoxib) has been
      countered by an increased incidence of myocardial infarction and stroke detected
      in 5 placebo controlled trials involving the COX-2 inhibitors celecoxib,
      rofecoxib and valdecoxib. The future of COX-2 inhibitors will be an example of
      personalised medicine as their use will be restricted to patients who do not
      respond to tNSAIDs or with increased risk of GI complications.

PMID- 16415489
TI  - Angiotensin converting enzyme (ACE) and HydroxyMethylGlutaryl-CoA (HMG-CoA)
      reductase inhibitors in the forefront of pharmacology of endothelium.
AB  - Healthy endothelium is essential for undisturbed functioning of the
      cardiovascular system, while endothelial dysfunction leads to its various
      pathologies. For example endothelial dysfunction precedes clinical symptoms of
      atherothrombosis, such as acute coronary syndrome, ischemic stroke, peripheral
      arterial disease or diabetic microangiopathies e.g. retinopathy and nephropathy.
      Accordingly, pharmacological reversal of endothelial dysfunction may represent a
      new approach in preventing the aforementioned vasculopathies. In modern
      cardiovascular pharmacology, inhibitors of angiotensin converting enzyme (ACE-I)
      or inhibitors of HydroxyMethylGlutaryl-CoA (HMG-CoA) reductase (statins) are
      among the most widely used cardiovascular drugs. Originally, ACE-I and statins
      were introduced to clinical medicine to lower arterial blood pressure or to lower
      blood LDL cholesterol levels, respectively. They were respectively targeted to
      inhibit ACE in blood or to inhibit HMG-CoA reductase in the liver. Surprisingly,
      these two classes of drugs apart from their classic mechanisms of action exert
      pleiotropic endothelial actions, which involve the inhibition of ACE or HMG-CoA
      reductase within the endothelium, as well as other less understood endothelial
      mechanisms. Typically, therapeutic effectiveness of ACE-I by far exceeds the
      benefits expected from their hypotensive effect or as the matter of fact of other
      hypotensive drugs. Similarly, statins offer cardiovascular protection
      irrespective of initial LDL cholesterol levels in patients. In our view, it is
      the endothelial action of ACE-I or statins that contributes significantly to
      their anti-inflammatory, anti-thrombotic, and vasculoprotective actions.
      Importantly, actions of ACE-I or statins are not limited to the correction of
      functioning of a single endothelial mediator, but they do possess a broader
      spectrum of endotheliotropic properties that proved efficient in preventing
      atherothrombosis and other vasculopathies. Quite surprisingly, the history of ACE
      I and statins has a major impact for the future development in pharmacology of
      endothelium.

PMID- 16415490
TI  - Polyphenols as potential therapeutical agents against cardiovascular diseases.
AB  - Increasing evidence suggests that polyphenols from fruits, vegetables and
      beverages such as wine and tea may exert protective effects on the cardiovascular
      system. Indeed, research in the field of polyphenols points out their antioxidant
      and free radical scavenging properties, leading to lower low-density lipoprotein
      (LDL) oxidation and platelet aggregation. These compounds are also able to
      modulate the generation of nitric oxide (NO) from vascular endothelium and to
      interfere with the mechanisms leading to inflammation and endothelial apoptosis,
      contributing to the prevention of the endothelial dysfunction, known to play a
      central role in the pathogenesis of cardiovascular diseases. This article reviews
      the potential targets of polyphenols involved in the complex pathophysiological
      events occurring in cardiovascular diseases, such as hypertension,
      atherosclerosis and stroke.

PMID- 16415491
TI  - Role of nitric oxide, nitroxidative and oxidative stress in wound healing.
AB  - Redox-regulated processes are relevant to wound healing. A balance between
      bioavailable nitric oxide (NO) concentration and a level of oxidative and
      nitroxidative stress in wounds may be crucial in wound repair. The highly
      beneficial effect of bioavailable NO is attributed to scavenging of superoxide,
      which is the main component of oxidative stress. Also, the high level of NO can
      influence angiogenesis and endothelial/skeletal muscle cell remodeling and
      proliferation. However, under conditions of excessive and prolonged production of
      O(2)(-) in wounds, the supplementation of NO can be evolved in significant
      increase in nitroxidative stress due to production of peroxynitrite (ONOO(-)) and
      peroxynitrous acid (ONOOH). ONOOH can trigger a cascade of events leading to the
      generation of highly reactive and damaging radicals and oxidative species. These
      species (mainly CO(3)(.-), NO(2)(+), NO(2), N(2)O(3), OH(.)) can impose
      significant damage in biological milieu and impair the process of wound healing.
      Therefore, a general strategy for an acceleration of the wound healing process
      may include an intervention(s) leading to the decrease in oxidative stress
      (treatment with antioxidants and/or prevention of O(2)(-) generation by uncoupled
      constitutive nitric oxide synthase, cNOS) and delivery of NO (treatment with NO
      donors, cNOS gene therapy). Here we briefly review the role of NO, and focus on
      O(2)(-) and ONOOH (major components of oxidative and nitroxidative stress
      respectively) in the normal and impaired process of wound healing.

PMID- 16415492
TI  - Prostacyclin in the cardiovascular system: new aspects and open questions.
AB  - Several indications exist that prostacyclin (PGI(2)) release in the
      cardiovascular system might be affected by cyclooxygenase (COX)-2-specific
      inhibitors. This could reflect an inhibition of PGI(2) synthesis in the
      endothelium although in these cells mainly COX-1 is expressed. Inflammation and
      stress induce COX-2 in smooth muscle cells which could have happened in patients
      with cardiac diseases. Herein, we show that also cardiomyocytes contain PGI(2)
      synthase in intercalated discs as a third source of PGI(2) in the cardiovascular
      system. Another aim of this study was to explain the finding that PGI(2) synthase
      in lipopolysaccharide (LPS)-treated smooth muscle cells, in contrast to
      endothelial cells, is resistant to nitration and inhibition by peroxynitrite. By
      using redox cyclers, the nitration occurred and confirmed our previous hypothesis
      that a high peroxidative activity of such cells keeps peroxynitrite below the
      effective levels of 50 nM. Considering enhanced oxidative stress in aged vessels,
      we postulated and verified that endothelial dysfunction in aged vessels is due to
      nitration and inhibition of PGI(2) synthase. Such data underline the role of
      PGI(2) as a potent mediator for regaining and maintaining the normal resting
      state of cells in a COX-2 dependent fashion.

PMID- 16415493
TI  - Hypertriglyceridemia but not hypercholesterolemia induces endothelial dysfunction
      in the rat.
AB  - In humans, hypercholesterolemia and hypertriglyceridemia induce endothelial
      dysfunction and therefore lead to atherosclerosis. In contrast, rats are
      resistant to atherosclerosis. Here we analyze whether rats respond to
      hypercholesterolemia and hypertriglyceridemia by developing of endothelial
      dysfunction. To induce hypercholesterolemiaWistar-Kyoto (WKY) and spontaneous
      hypertensive (SHR) rats were fed for 12 weeks with AIN93 diet supplemented with
      cholesterol (1%) and butter (20%). To induce hypertriglyceridemiaWistar were fed
      for 8 weeks with AIN93 diet supplemented with 60% fructose. In all experimental
      groups nitric oxide (NO)-dependent and prostacyclin (PGI(2))-dependent function
      was assessed in the isolated aorta. Additionally in hypertriglyceridemic rats
      endothelial function in the isolated mesenteric resistance artery was analyzed.
      NO-dependent vasodilation induced by acetylcholine or histamine in aorta of SHR
      and WKY rats was modestly impaired. Hypercholesterolemic diet fed to WKY and SHR
      rats induced a rise in total cholesterol and low-density lipoproteins (LDL)
      cholesterol by 2.5 and 4.5 fold, respectively, but did not further impair NO
      dependent vasodilation. Although basal production of PGI(2) in aortic rings from
      SHR rats was five fold higher than in aortic rings from WKY rats, the
      hypercholesterolemic diet did not further affect aortic PGI(2) production in
      either rat strain. Endothelium-independent vasodilation induced by SNAP remained
      also unchanged. On the other hand, the hypertriglyceridemic diet given to Wistar
      rats led to a selective 1.5-2 fold elevation of triglycerides that was associated
      with the impairment of NO-dependent relaxation in aorta as well as in the
      mesenteric resistance artery. Interestingly, the basal production PGI(2) by
      aortic rings was not modified by hypertriglyceridemic diet. Again endothelium
      independent relaxation induced by S-nitroso-N-acetyl-penicilamine (SNAP) was not
      affected. In summary, although in humans both hypercholesterolemia and
      hypertriglyceridemia are associated with endothelial dysfunction, in rats
      hypertriglyceridemia only led to the impairment of NO-dependent vasodilation.
      Hypercholesterolemia did not modify endothelial function even in hypertensive
      rats that display pre-existing alterations in vasodilator function.

PMID- 16415494
TI  - Opposite effects of beta amyloid on endothelial cell survival: role of fibroblast
      growth factor-2 (FGF-2).
AB  - Amyloid beta-peptides (Abeta) aggregate during Alzheimer's disease contributing
      to the development of the pathology. At micromolar concentration Abeta is toxic
      and accumulates in neurons and in the vasculature. However, Abeta is found at
      nanomolar concentrations in the plasma of healthy individuals and is also
      produced by endothelial cells. Here, we investigate the dual role exerted by
      Abeta(1-40) on endothelial cell functions. Coronary vascular endothelial cells
      were utilized to study whether Abeta affects endothelial cell growth and its
      action was compared with the effect of fibroblast growth factor-2 (FGF-2). In a
      range from 5 to 100 nM, Abeta(1-40) concentration-dependently increased cell
      growth, whereas higher concentrations of Abeta(1-40) reduced cell number compared
      to control. At nanomolar concentration of the peptide Abeta(1-40) also stimulated
      FGF-2mRNA expression and protein production, which was negatively affected by
      micromolar concentration of the peptide. The dual role observed on endothelial
      cell growth, was mediated by FGF-2 biodisponibility. In fact, neutralizing anti
      FGF-2 antibody inhibited Abeta(1-40)-induced ERK1/2 phosphorylation at 50 nM. 5
      muM inhibited ERK1/2 activation over control and this was reflected by diminished
      cell growth which was recovered by exogenous FGF-2 administration. These results
      suggest that low Abeta concentrations stimulate endothelial cells to acquire an
      angiogenic phenotype through interaction with endogenous FGF-2 and induction of
      its synthesis. In contrast, accumulation of Abeta results toxic for endothelial
      cells and at these concentrations Abeta peptide looses its ability to prime FGF-2
      cycle. This may be a fundamental pathological event which might contribute to the
      worsening of the pathology.

PMID- 16415495
TI  - Abnormalities of the resistance vasculature in hypertension: correction by
      vasodilator therapy.
AB  - The structure of the resistance vessels in patients with essential hypertension
      is altered, with reduction of the lumen diameter and increase in wall-to-lumen
      ratio without change in wall mass, known as eutrophic remodelling. The alteration
      appears to cause a reduction in the vascular reserve, in particular the coronary
      reserve (the ability to increase blood flow during hyperaemia). Successful
      treatment of hypertension should therefore seek not only to reduce blood pressure
      but also to normalize the structure of the resistance vessels. The available
      evidence shows that the effect of antihypertensive treatment on resistance vessel
      structure is variable and not related to the reduction in blood pressure. Instead
      it appears that the key feature allowing normalization of vascular structure is
      the ability of the treatment to cause a reduction in total peripheral resistance.
      Thus beta-blocker treatment is apparently unable to correct the abnormal vascular
      structure, although vasodilator treatment - for example with angiotensin
      coverting enzyme (ACE)-inhibitors - is able to do this. In vivo studies in rats,
      and in vitro organ culture experiments have suggested that the remodelling is
      related to the activation of the vascular smooth muscle. The process seems to be
      mediated at least in part by tissue transglutaminase, an enzyme which
      specifically controls the interaction of smooth muscle with the extracellular
      matrix. Taken together the data support the desirability of vasodilator therapy
      in the treatment of essential hypertension.

PMID- 16415496
TI  - Coronary microvascular dysfunction and idiopathic dilated cardiomyopathy.
AB  - There is growing evidence of the presence and relevance of coronary microvascular
      abnormalities in many cardiac diseases. In particular, it has been recently shown
      that dilated cardiomyopathy (DCM) is characterized by dysfunction of the coronary
      microvessels since its very early onset. Coronary microcirculatory dysfunction is
      not an effect of myocardial damage but seems in turn to cause progressive
      contractile impairment, ventricular dilation and heart failure. The mechanisms of
      the progressive deterioration of cardiac function in DCM are largely unknown but
      both myocardial hypoperfusion and myocardial ischemia at the microvascular level
      are most probably involved. It has been demonstrated that the presence and the
      extent of coronary microcirculatory dysfunction in patients with early stage DCM
      is an independent and relevant predictor of worse prognosis. From these studies
      it is more and more evident that the coronary microcirculation is involved in the
      pathogenesis ofDCMand should be considered a new target of treatment in those
      cardiac diseases at risk to evolve towards heart failure.

PMID- 16415497
TI  - Advanced glycation and retinal pathology during diabetes.
AB  - Of all microvascular complications of diabetes mellitus, retinopathy remains the
      most common. This disease presents major therapeutic problems for the
      ophthalmologist and despite many decades of intense research it still constitutes
      a major cause of blindness in the Western world. This review outlines the
      pathological characteristics of diabetic retinopathy and proposes a link between
      disease progression with the formation and accumulation of advanced glycation
      endproducts (AGEs). AGEs form in vivo from the reaction of glucose and/or alpha
      oxaloaldehydes leading to chemical modifications on the amino groups of proteins,
      lipids and DNA. These heterogenous adducts can modify the structure and function
      of proteins and lead to intra-molecular and intermolecular cross-link formation.
      As reported in a range of clinical investigations and determined by mechanistic
      in vitro and in vivo studies, AGEs accumulate in the diabetic retina where they
      may be effectors of retinal vascular and neural cell dysfunction. Evidence now
      points towards a pathogenic role for advanced glycation in the initiation and
      progression of diabetic retinopathy and this review will examine the current
      state of knowledge of AGE-related pathology in the retina at a cellular and
      molecular level. It will also describe how ongoing pharmaceutical strategies to
      inhibit AGE formation and thereby attenuate their pathogenic influence during
      chronic hyperglycemia may play a significant role in the treatment of diabetic
      retinopathy.

PMID- 16415498
TI  - Inflammatory lipid mediators in ischemic retinopathy.
AB  - Ischemic proliferative retinopathy develops in various retinal disorders,
      including retinal vein occlusion, diabetic retinopathy and retinopathy of
      prematurity. Ischemic retinopathy remains a common cause of visual impairment and
      blindness in the industrialized world due to relatively ineffective treatment.
      Oxygen-induced retinopathy (OIR) is an established model of retinopathy of
      prematurity associated with vascular cell injury culminating in microvascular
      degeneration, which precedes an abnormal neovascularization. The retina is a
      tissue particularly rich in polyunsaturated fatty acids and the ischemic retina
      becomes highly sensitive to lipid peroxidation initiated by oxygenated free
      radicals. Retinal tissue responds to physiological and pathophysiological stimuli
      by the activation of phospholipases and the consequent release from membrane
      phospholipids of biologically active metabolites. Activation of phospholipase
      A(2) is the first step in the synthesis of two important classes of lipid second
      messengers, the eicosanoids and a membrane-derived phospholipid mediator platelet
      activating factor (PAF). These lipid mediators accumulate in the retina in
      response to injury and a physiologic role of these metabolites in retinal
      vasculature remains for the most part to be determined; albeit proposed roles
      have been suggested for some. The eicosanoids, in particular the prostanoids,
      thromboxane A(2) (TXA(2)) and PAF are abundantly generated following an oxidant
      stress and contribute to neurovascular injury. TXA(2) and PAF play an important
      role in the retinal microvacular degeneration of OIR by directly inducing
      endothelial cell death and potentially could contribute to the pathogenesis of
      ischemic retinopathies. This review focuses on mechanisms that precede the
      development of neovascularization, most notably regarding the role of lipid
      mediators that partake in microvascular degeneration.

PMID- 16415499
TI  - Purinoceptors in renal microvessels: adenosine-activated and cytochrome P450
      monooxygenase-derived arachidonate metabolites.
AB  - Cytochrome P450 (CYP)-dependent epoxyeicosatrienoic acids (EETs) dilate rat
      preglomerular microvessels (PGMVs) when adenosine 2A receptors (A(2A)R) are
      stimulated. As high salt intake increases epoxygenase activity and adenosine
      levels, we hypothesized that renal adenosine responses would be greater in high
      salt-fed rats. We have obtained evidence supporting this hypothesis in rats fed a
      high salt diet for 7 days. Stimulation of adenosine receptors with 2
      chloroadenosine in kidneys obtained from rats on high salt (4%) intake produced
      an increase in EET release that was several-fold greater than in kidneys of rats
      on normal salt (0.4% NaCl) diets, which was associated with a sharp decline in
      renovascular resistance. Under conditions of high salt intake, an associated
      upregulation of A(2A)R and 2C23 protein expression was observed. As EETs are
      renal vasodilator and natriuretic eicosanoids, the antipressor response to salt
      loading may operate through an A(2A)R - EET mechanism. These findings expand the
      role of adenosine-related mechanisms in protecting renal function.

PMID- 16415500
TI  - Inflammatory pathways and microvascular responses in the lung.
AB  - Neutrophil granulocytes constitute an important host defense mechanism, but may
      at the same time damage functional tissue and propagate acute organ failure. This
      balance is particularly vulnerable in the lung which provides a large surface
      area for invading pathogens and microorganisms, and simultaneously harbors a
      large pool of physiologically marginated neutrophils within its microvascular
      bed. Pathophysiological stimuli further amplify this accumulation of blood cells
      and promote the emigration of neutrophils into the pulmonary interstitium and the
      airspaces by different mechanisms depending on the pathophysiological stimulus,
      its route of entry into or site of production in the lung, and the time course of
      its action. Importantly, the pulmonary microvascular endothelium plays a key role
      in regulating not only sequestration and emigration of neutrophils, but by
      initiating the inflammatory response to a variety of diverse stimuli many of
      which do not directly target the circulating neutrophil, but elicit microvascular
      reactions by primarily acting on the endothelium. This review highlights the
      inflammatory process in the pulmonary microvasculature with special emphasis on
      the role of the pulmonary endothelium.

PMID- 16415501
TI  - Mechanisms of platelet-activating factor (PAF)-mediated responses in the lung.
AB  - Platelet-activating factor (PAF) is a potent lipid mediator that has been
      implicated in asthma, sepsis, acute lung injury and ischemia/reperfusion injury.
      Its actions in the lungs include vasoconstriction, bronchoconstriction, and edema
      formation. Despite the fact that PAF exerts these actions within minutes, they
      are mediated by other lipid mediators, in particular eicosanoids generated by
      cyclooxygenase and lipoxygenase enzymes and sphingolipids generated by acid
      sphingomyelinase.We will discuss the mechanisms of the PAF-induced pressor
      responses that are triggered by thromboxane A(2) and leukotrienes, as well the
      PAF-induced increase in vascular permeability that is mediated by prostaglandin
      E(2) (PGE(2)) and ceramide.

PMID- 16415503
TI  - Atherosclerosis and angiogenesis: what do nerves have to do with it?
AB  - Neuropeptide Y (NPY) is a sympathetic neurotransmitter and a stress mediator with
      pleiotropic activities mediated by multiple receptors, Y1-Y5. Originally known as
      an appetite stimulant and a vasoconstrictor, NPY has recently emerged as a growth
      factor for a variety of cells from vascular smooth muscle to neural precursors -
      implicating the peptide in atherosclerosis and tissue remodeling. NPY is also
      potently angiogenic, and was hailed as a potential candidate for a nerve-driven
      ischemic revascularization. To determine if the latter, beneficial activity of
      the peptide can be separated from its deleterious pro-atherosclerotic action -
      receptor specificity and mechanisms of this "Janus phenomenon" were studied.
      Expression of Y2 receptors on the endothelium, and Y1 receptors on vascular
      smooth muscle, were required for angiogenic and pro-atherosclerotic activities,
      respectively. Amplification of both activities was provided by co-expression of
      Y5 receptors. In rodent models, limb ischemia up-regulated the NPY-Y2 system,
      which contributed to post-ischemic revascularization; exogenous NPY further
      augmented it and nearly normalized blood flow and function of ischemic tissues.
      NPY-induced angiogenesis was also dependent on nitric oxide and endothelial
      dipeptidyl peptidase IV (DPPIV, which converts NPY to Y2/Y5-selective agonist),
      but resistant to Y1 receptor blockade. Conversely, vascular angioplasty up
      regulated the NPY-Y1 system and promoted atherosclerosis and hyperplastic
      remodeling, and these activities were blocked by Y1 receptor antagonist and
      augmented by DPPIV inhibitors. Thus, drugs targeting specific NPY receptors may
      become new therapeutics against atherosclerosis/restenosis (Y1-selective
      antagonists) or for ischemic revascularization (Y2-selective agonists). Such
      drugs may be particularly beneficial for patients with elevated circulating NPY
      levels e.g. by chronic stress.

PMID- 16415504
TI  - Lidocaine-induced apoptosis and necrosis in U937 cells depending on its dosage.
AB  - Local anesthetics are known to affect a variety of cellular responses other than
      the action of anesthetics through the Na(+) channel blockade. In this study, we
      examined the effect of a common local anesthetic lidocaine on the cellular
      activity and viability of human histiocytic lymphoma U937 cells. The cellular
      activity and viability were assessed by WST-1 reduction activity and trypan blue
      exclusion test, respectively. Induction of apoptosis was monitored by DNA ladder
      formation, reduction of mitochondrial transmembrane potential (DeltaPsim),
      caspase-3 activity and nuclear morphology. Lidocaine at concentrations below 12
      mM induced apoptosis characterized by DNA fragmentation and chromatin
      condensation dose- and time-dependently. A pan-caspase inhibitor and a caspase-3
      inhibitor blocked DNA ladder formation followed by the reduction of cell death.
      However, the caspase inhibitors did not affect the DeltaPsim, but cyclosporin A
      inhibited the collapse of DeltaPsim followed by a reduction of cell death.
      Lidocaine-induced apoptosis was mitochondria- and caspase-dependent, but the
      collapse of DeltaPsim was independent of caspase activation. At concentrations
      above 15 mM, lidocaine induced necrosis with early disruption of membrane
      integrity. These results indicate that lidocaine induced apoptosis and necrosis
      in U937 cells depending on its dosage.

PMID- 16415502
TI  - Rabbit erythrocytes possess adenylyl cyclase type II that is activated by the
      heterotrimeric G proteins Gs and Gi.
AB  - Adenosine triphosphate (ATP) release from rabbit erythrocytes occurs in response
      to deformation or reduced oxygen tension. A signal transduction pathway that
      relates these stimuli to ATP release has been proposed. This pathway includes the
      heterotrimeric G proteins, Gs and Gi, adenylyl cyclase, protein kinase A, and the
      cystic fibrosis transmembrane conductance regulator. Importantly, adenylyl
      cyclase types II, IV and VII have been reported to be activated by both Gs and
      Gi. Here, we demonstrate that rabbit erythrocytes possess an adenylyl cyclase
      subtype that is activated both by the alpha subunit and the betagamma subunit of
      Gs and Gi, respectively. Washed rabbit erythrocytes released ATP when exposed to
      the beta adrenergic receptor-mediated activator of Gs, isoproterenol (ISO, 10
      microM, n = 8, p < 0.05) as well as in response to incubation with a direct
      activator of Gi, mastoparan 7 (MAS7, 10 microM, n = 12, p < 0.05). In contrast,
      an inactive mastoparan derivative, mastoparan 17 (MAS 17, 10 microM, n = 6) did
      not stimulate ATP release. Importantly, incubation of washed rabbit erythrocytes
      with either isoprotenerol (ISO) (10 microM, n = 7) or MAS7 (10 microM, n = 11)
      resulted in increases in cyclic adenosine monophosphate (cAMP) (p < 0.01).Western
      analysis was used to determine if an adenylyl cyclase capable of being activated
      by both Gs and Gi was a component of rabbit erythrocyte membranes. We identified
      adenylyl cyclase type II with two antibodies generated against different epitopes
      of the protein. These results provide support for the hypothesis that, in rabbit
      erythrocytes, activation of either Gs or Gi results in the stimulation of
      adenylyl cyclase resulting in increases in cAMP leading, ultimately, to the
      release of ATP.

PMID- 16415505
TI  - Cannabinoid suppressed bicuculline-induced convulsion without respiratory
      depression in the brainstem-spinal cord preparation from newborn rats.
AB  - Previous studies have suggested that cannabinoid compounds are anticonvulsants
      and that these compounds depress respiratory activity. However, the
      anticonvulsant potential of cannabinoids and their depressive effect on
      respiration have not been evaluated simultaneously. In the present study, we used
      a brainstem-spinal cord preparation model to investigate changes in inspiratory
      activity and the anticonvulsant effects of a cannabinoid receptor agonist, WIN
      55, 212-2, in bicuculline-induced convulsion. Application of 10 microM WIN 55,
      212-2 caused no change in inspiratory activity (6.9+/- 0.89 bursts/min vs. 8.0+/-
      1.3 bursts/min, not significant) and decreased bicuculline-induced seizure-like
      nerve activity (number of seizure-like activities in 10 min, 11+/- 7.4 bursts vs.
      1.5+/- 1.6 bursts, P< 0.01; average duration of seizure-like activity, 8.9+/- 4.0
      sec vs. 4.7+/- 2.1 sec, P> 0.01). Our results suggest that administration of an
      appropriate dose of cannabinoid receptor agonist WIN 55,212-2 has an
      anticonvulsant effect but does not cause respiratory depression.

PMID- 16415507
TI  - Characterization of the peri-implant epithelium in hamster palatine mucosa:
      behavior of Merkel cells and nerve endings.
AB  - The purpose of this study was to investigate the relationship between Merkel
      cells and nerve elements during tissue regeneration after receiving dental
      implants. Golden hamsters were divided into 3 groups and titanium alloy implants
      were fixed in their left-side maxilla through the third palatine rug. Animals
      were sacrificed at 1, 2, 3, 4, 5, 6, and 7 days after the implantation and
      tissues were characterized at the immunohistochemical and morphological levels.
      CK 20 and PGP 9.5 antibodies which react with Merkel cells and nerve fibers were
      used. Immunohistochemically, no CK 20-positive Merkel cells were seen in the peri
      implant epithelium throughout the 7 days. However, starting at day 4, PGP 9.5
      positive nerve fibers appeared in the connective tissue, and by day 7, nerve
      fibers had invaded the more superficial layer of the peri-implant epithelium
      compared to the mucosa removal control group. At the electron microscopic level,
      the intercellular spaces of the regenerating epithelium in the mucosa removal
      control group were small. In contrast, intercellular spaces of the peri-implant
      epithelium tended to be wide and regenerating nerve fibers invaded those
      intercellular spaces. In both the mucosa removal control group and the
      implantation group, the basal lamina and connective tissues regenerated
      completely. However, clear Merkel cells containing neurosecretory granules were
      not observed. Taken together, our results indicate that Merkel cells in the
      hamster palatine mucosa do not regenerate in the peri-implant epithelium.
      However, regenerative nerve fibers seem to play essential roles as part of the
      defense and sensory systems around the peri-implant epithelium to compensate for
      the weakened defense mechanism.

PMID- 16415506
TI  - Intraperitoneal injection of lactoferrin ameliorates severe albumin extravasation
      and neutrophilia in LPS-induced inflammation in neonatal rats.
AB  - Lactoferrin (LF) plays various anti-inflammatory roles in inflammation
      experimentally induced by lipopolysaccharides (LPS). But the effects of LF on
      albumin extravasation and neutrophilia have not been elucidated. We aimed to
      study the effects of LF on albumin extravasation, neutrophilia and/or on other
      symptoms in inflammation caused by LPS in rats. Human lactoferrin (hLF) was
      injected (10 mg/100 mL in PBS) 18 h, or 15 min prior to, or 60 min after
      intraperitoneal injection of LPS in 13 days old Sprague Dawley rats. Prophylactic
      injection of hLF significantly ameliorated albumin extravasation in ascitic fluid
      at 5 h and neutrophilia in the blood at 24 h after LPS injection, but the after
      injection of hLF did not. Interestingly, an injection of rat anti-TNFalpha IgG 15
      min prior to LPS injection did not ameliorate albumin extravasation. Prophylactic
      injection of hLF significantly ameliorated other symptoms like mortality, and the
      decrease of phagocytotic activity of peritoneal polymorpho-nuclear leukocytes
      (PMNL), but did not ameliorate the decrease of platelets in the plasma. These
      findings suggest that hLF may be available as a medical treatment prior to
      surgery for prophylaxis of side effects like albumin extravasation or
      neutrophilia.

PMID- 16415508
TI  - Cellular distribution of glutamate transporters in the gastrointestinal tract of
      mice: an immunohistochemical and in situ hybridization approach.
AB  - L-Glutamate transport by intestinal epithelial cells is an initial step of the
      entire glutamate metabolism pathway in the gut mucosa. The present study examined
      the cellular distribution of glutamate transporters in the digestive tract of
      adult mice using immunohistochemistry and in situ hybridization technique.
      Expression of EAAC1 mRNA was more intense in the ileum, where the epithelium in
      crypts and the basal half of intestinal villi showed high levels of transcripts,
      suggesting an essential role of EAAC1 in differentiating or premature epithelial
      cells. Electron-microscopically, EAAC1 immunoreactivity was predominantly
      localized in the striated border of enterocytes. Immunoreactivity for GLT-1 was
      found in the lateral membrane of epithelial cells at the bottom of gastric glands
      and at the intestinal crypts, and also in the lateral membrane of secretory cells
      at the duodenal gland. GLAST immunoreactivity was restricted to the fundic and
      pyloric glands, and was especially intense in the neck portion of both glands.
      However, in situ hybridization analysis failed to confirm the expression of GLT-1
      and GLAST at the mRNA level, possibly due to limited sensitivity. The strong and
      specific luminal localization of EAAC1 in the intestinal epithelium suggests that
      EAAC1 is a predominant transporter of glutamate, at least in the lower part of
      the small intestine.

PMID- 16415509
TI  - Structure and component alteration of rabbit Achilles tendon in tissue culture.
AB  - The aim of this study was to investigate alterations of cultured tendon tissues
      to determine whether tissue culture is a useful method for biological analyses of
      the tendon. Tendon tissues for tissue culture were isolated from Achilles tendons
      of rabbits. The tendon segments were placed one segment per well and incubated in
      growth medium consisting of Dullbecco's modified Eagle's medium supplemented with
      5% fetal bovine serum at 37 degrees C in a humidified atmosphere with 5% CO(2)
      for various periods. The alignment of collagen fibrils was preserved for 48 h,
      but tendon structure has disintegrated at 96 h. Alcian blue staining and gelatine
      zymography revealed that proteoglycan markedly diminished and that matrix
      metalloproteinase (MMPs) activity was upregulated sharply at 72 and 96 h. The
      ratio of collagen fibrils with large diameter had increased and the mean diameter
      and mass average diameter value had reached maximum at 48 h. The values then
      decreased and mean diameters at 72 and 96 h were significantly different from
      that at 48 h. At 96 h, the ratio of collagen fibrils with small diameters had
      increased and collagen fibrils with large diameters had disappeared. These
      findings indicate that structural alteration is possible to be induced by
      disintegration of collagen fibrils and disappearance of glycosaminoglycans from
      extracellular matrix (ECM), subsequent of upregulation of MMPs activity. Although
      the study period is limited, the tissue culture method is available for
      investigating cell-ECM interaction in tendons.

PMID- 16415510
TI  - Demonstration of microvessel networks and endothelial cell phenotypes in the
      normal murine lung.
AB  - The vascular endothelial cells (ECs) express various antigens related to
      coagulation factors, including factor VIII-related antigen or von Willebrand
      factor (vWF) in the cytoplasm and thrombomodulin (TM; a thrombin receptor)along
      the plasma membrane. CD34 (a hematogenic stem cell marker) is also expressed
      along the surface membrane of the ECs. Using these EC markers and fluorescein
      isothiocyanate-labeled dextran (FITC-dextran)(Sigma Co., St. Louis, MO), we
      attempted to demonstrate the complex network of microvessels and their EC
      phenotypes in tracheo-bronchial trees and lung parenchyma of the normal adult ICR
      male mice. Under anesthesia, saline with heparin was infused slowly through left
      ventricle to drain off the blood. Following brief fixation with 4% buffered
      paraformaldehyde solution (PFA) through the same route, one group of animals
      received, 1) FITC-dextran injection via left ventricle, and the large airways and
      lungs were further fixed in PFA, or 2) The airways and lungs of the other group
      were rapidly frozen, and the thin sections were stained with two antibodies of
      vWF and Alexa Fluor 594-labeled CD34. The vWF antibody was later labeled by FITC.
      The microvessels of airways and lungs were observed by a laser scanning confocal
      microscope (TC-SP, Leica, Heidelberg, Germany). The phenotypic characteristics of
      microvessel ECs appeared mostly identical with those described previously in the
      human lung, although CD34 was applied instead of TM in the present study. The
      topographical heterogeneity of immunohistochemical properties of ECs would
      suggest functional differences at different sites of the lung, that would provide
      a novel insight for understanding the pathogenesis of human lung diseases.

PMID- 16415511
TI  - Steroid Hormones, their receptors and neuroendocrine system.
AB  - The brain is an important target organ for circulating steroid hormones secreted
      from peripheral organs such as the adrenal cortex, testis and/or ovary. In other
      words, these peripheral organs control the central nervous system. Steroid
      hormones substantially influence brain development, reproduction, sexual
      differentiation, cognition, memory, behavior, and so on. These effects are
      mediated by steroid hormone receptors, which directly regulate gene expression.
      The steroid hormone receptor superfamily is an intracellular ligand-regulated
      transcription factor. All members, including the glucocorticoid receptors (GR),
      mineralocoroticoid receptors (MR), estrogen receptors (ER), progesterone
      receptors (PR) and androgen receptor (AR), mediate the expression of a gene by
      binding to hormone responsive elements (HREs) as dimmers in a ligand-dependent
      manner. In particular, steroid hormones have an important role for the regulating
      neurons and cells, which are associated with the neuroendocrine and endocrine
      regulation system, because many neuroendocrine neurons and cells express the
      steroid hormone receptors, such as estrogen receptor (ER), androgen receptor (AR)
      and corticosteroid receptors. In this review, first the localization of GR and MR
      immunoreactivities in the brain is introduced, and secondly, the effects of
      change of GR expression in neurons are examined by several morphological
      approaches. Third, the interaction of GR expression and pituitary cell function
      is introduced. Finally, the recent topics on the control system of feeding
      regulation in the central nervous system, which also closely involves steroid
      hormone action, are discussed.

PMID- 16415512
TI  - Modifier genes and oligogenic disease.
AB  - It is now increasingly apparent that modifier genes have a considerable role to
      play in phenotypic variations of single-gene disorders. Intrafamilial variations,
      altered penetrance, and altered severity are now common features of single gene
      disorders because of the involvement of several genes in the expression of the
      disease phenotype. Oligogenic disorders occur because of a second gene modifying
      the action of a dominant gene. It is now certain that cancer occurs due to the
      action of the environment acting in combination with several genes. Although
      modifier genes make it impossible to predict phenotype from the genotype and
      cause considerable difficulties in genetic counseling, they have their uses. In
      the future, it is hoped that modifier genes will allow us to understand cell and
      protein interactions and thus allow us to understand the pathogenesis of disease.

PMID- 16415513
TI  - Growth hormone enhances natural killer cell activity against glioma.
AB  - Although it is now known that pituitary hormones activate the immune system,
      there are still numerous questions to be answered with regard to the mechanisms
      involved. In this study, which focuses on growth hormone (GH) and natural killer
      (NK) cells, the latter's antitumor effects on glioma were investigated. Using
      fluorescein isothiocyanate-labeled rat 9L glioma and NK-receptive YAC-1 cells as
      target cells and rat splenocytes as effector cells, a cytotoxicity assay was
      carried out with the fluorescence-activated cell sorter method, which stains dead
      cells with propidium iodide. The effector cells were pretreated 48 hours in
      advance with various concentrations of GH. A similar experiment was also carried
      out in the presence of anti-asialo-GM1 antibodies. When the GH concentration of
      9L was 10 to 40 microg/ml, cytotoxicity was confirmed to have been enhanced 17%
      to 39%. This enhancement disappeared in the presence of anti-asialo-GM1
      antibodies. A similar increase in cytotoxic activity was also confirmed in YAC-1
      cells. In this experiment we observed GH enhancement of natural killer activity
      against glioma.

PMID- 16415514
TI  - Helicobacter pylori Infection among patients visiting a clinic in Kasama City,
      Ibaraki Prefecture.
AB  - We examined Helicobacter pylori infection in patients who visited the Iso Clinic
      (Kasama City, Ibaraki Prefecture) with abdominal complaints, and determined the
      prevalence of H. pylori infection by age, sex, endoscopic diagnosis, abdominal
      complaint, gastric mucosa, and living environment. Peptic ulcer disease was
      observed in 23.2% of the patients examined with endoscopy, but there was no
      association between abdominal complaints and the prevalence of H. pylori
      infection. The prevalence of H. pylori infection was high among patients with
      peptic ulcer disease and atrophic gastritis. The prevalence of H. pylori
      infection was higher in the generation born before tae start of the period of
      rapid economic growth (71.5%) than in the generation born afterward (64.8%). No
      significant difference was observed between males and females. The prevalence of
      H. pylori infection was high in those who drank well water during childhood and
      those who were raised in a house with a nonflushing of toilet (67.2% and 67.5%,
      respectively). There were no associations with river basin of residence, alcohol
      consumption, or smoking. The prevalence of H. pylori infection among patients who
      visited Iso Clinic was higher than that among patients seen at Tama-Nagayama
      Hospital, Nippon Medical School (Tama City, Tokyo). The difference is
      attributable to the higher prevalence of H. pylori infection in the elderly.

PMID- 16415515
TI  - Clinical aspects of infant leukemia--experiences of a single institution of
      Japan: high level of serum immunoglobulin M in infant leukemia.
AB  - The prognosis and clinical and biological characteristics of infant leukemia
      differ from those of leukemia in children 1 year or older. We reviewed the charts
      of patients younger than 1 year in whom leukemia was diagnosed from January 1981
      through December 2003 at our institution. Fourteen infants had leukemia, 6 had
      acute lymphoblastic leukemia (ALL), and 8 had acute myeloid leukemia (AML). The
      age of patients at diagnosis ranged from 2 to 11 months. Five of 8 AML patients
      presented with cutaneous manifestations, such as erythema and nodules, at
      diagnosis. Central nervous system (CNS) involvement was seen in 1 AML patient at
      diagnosis. Hyperleukocytosis of more than 50 x 10(9)/L was seen in 4 of 6 ALL
      patients and in 4 of 8 AML patients at diagnosis. All ALL patients showed a
      morphological diagnosis of L1 using the French-America-British classification
      system. For patients with AML, the morphological diagnoses were M0 for 1 patient,
      M2 for 1 patient, M4 for 2 patients (1 with eosinophilia), M5b for 2 patients,
      and M7 for 2 patients. One patient showing M7 morphology had Down syndrome.
      Surface markers were examined in 5 of 6 ALL patients and all AML patients. Five
      ALL patients showed a B-cell precursor immunophenotype. Two of 5 patients with
      ALL had CD10-positive leukemic cells and 3 of 5 patients with ALL had CD10
      negative leukemic cells. All AML patients were positive for CD13 or CD33 or both.
      Three of 5 patients with ALL showed abnormal chromosomes related to 11q. Six of 7
      patients with AML showed abnormal karyotypes. MLL gene rearrangements were seen
      in 3 (2 ALL, 1 AML) of 5 (2 ALL, 3 AML) patients. Serum immunoglobulin M levels
      were increased in 9 of 14 patients. Complete remission (CR) was achieved in all
      infants with ALL. Three patients relapsed and then died of the original disease.
      One of these 3 patients died after cord blood transplantation. Three ALL patients
      are alive without leukemia. CR was achieved in 6 of 8 AML patients. Four of 6
      patients are alive without leukemia. Infant leukemia patients in our institution
      had some special features. CNS involvement at diagnosis was seen in only 1
      patient and serum IgM levels were higher than those in children whose leukemia
      was diagnosed at 1 to 10 years of age.

PMID- 16415516
TI  - Effect of bicarbonated Ringer's solution on the acid-base balance in patients
      undergoing abdominal aortic aneurysm repair.
AB  - AIM: The present study was designed to assess whether prophylactic use of
      bicarbonated Ringer's solution ameliorates metabolic acidosis in patients
      undergoing aortic surgery. METHODS: Twenty patients undergoing elective
      infrarenal aortic aneurysm repair were randomly assigned to receive either
      bicarbonated Ringer's solution or acetated Ringer's solution. The pH, PaCO(2),
      and base excess (BE) were measured before surgical incision (T0), 5 min before
      reperfusion (T1), 5 min after reperfusion (T2), and 30 min after reperfusion
      (T3). Data were compared between the two groups. RESULTS: Both pH and BE
      initially showed a slight decrease in both groups during clamping. After
      unclamping of the aorta, an additional decrease in pH was observed in both groups
      (T0 to T2, and T3). There were no significant differences in pH between the
      groups throughout the study period. CONCLUSIONS: Aortic cross-clamping leads to
      the development of metabolic acidosis, with a decrease in pH and BE. The effect
      of administration of bicarbonated infusion fluid during elective abdominal aortic
      surgery had not significant compared with that of acetated Ringer's solution with
      respect to acid-base homeostasis.

PMID- 16415518
TI  - Three cases of retroesophageal right subclavian artery.
AB  - We have experienced three cases of retroesophageal right subclavian artery. Two
      cases were cadavers, and one case was a live human. In the two cadavers of a 68
      year-old and a 76-year-old, respectively Japanese and European males, the right
      subclavian artery originated from the aorta after the aorta branched the right
      carotid artery, the left carotid artery and the left subclavian artery. The right
      carotid artery immerged solely from the aorta. Where the right subclavian artery
      originated from the aorta, the artery took a dorsal direction. It passed between
      the esophagus and the vertebral column. The esophagus was compressed from the
      dorsal side by the right subclavian artery. The structural anomaly of the right
      subclavian artery accompanied the cephalad recurrence of the branch from the
      right vagal nerve toward the larynx. In the live human case, we obtained CT
      views. The patient was a 41-year-old Japanese, who complained of dysphagia
      lusoria. We found that the right subclavian artery was anomalous and originated
      from the aorta as the last cardinal branch in the thorax.

PMID- 16415517
TI  - Primary pulmonary mucosa-associated lymphoid tissue lymphoma combined with
      idiopathic thrombocytopenic purpura and amyloidoma in the lung.
AB  - Three abnormal shadows were detected in the right lung on chest X-ray films and
      computed tomography in a 75-year-old woman during follow-up for idiopathic
      thrombocytopenic purpura. Because a definitive diagnosis was not obtained through
      general examinations, exploratory thoracotomy was performed for diagnosis and
      treatment. The main lesion in the right middle lobe was diagnosed as mucosa
      associated lymphoid tissue (MALT) lymphoma according to histopathological
      findings, cytogenic studies and reverse transcriptase-polymerase chain reaction
      analysis, and nodular lesions in S(3) and S(7) were diagnosed with Congo-red
      staining as local deposition of amyloid. The patient had no recurrence of the
      MALT lymphoma of the lung or other organs for 4 years after surgery. To our
      knowledge, this is the first reported case of primary pulmonary MALT lymphoma
      combined with idiopathic thrombocytopenic purpura/lung amyloidoma.

PMID- 16415519
TI  - A case of Henoch-Schonlein purpura with rare complications: necrosis of the small
      intestine, neurological symptoms, and pericardial tamponade.
AB  - A case of Henoch-Schonlein purpura (HSP) with necrosis of the small intestine,
      neurological symptoms, and pericardial tamponade after frequent recurrence is
      described. Neurological symptoms were controlled well with steroid pulse therapy,
      and pericardial tamponade was treated successfully with pericardiocentesis and
      steroid pulse therapy. To treat necrosis of the small intestine, the necrotic
      tissue was excised and artificial anuses were constructed. Five months later, the
      small intestine was anastomosed in a curative operation. Periodic administration
      of coagulation factor XIII was required from the onset of symptoms until curative
      surgery, but the activity of this factor returned to normal levels after surgery
      operation. We report a case of Henoch-Schonlein purpura with extremely rare
      complications: necrosis of the small intestine, neurological symptoms, and
      pericardial tamponade.

PMID- 16415520
TI  - An asymptomatic heterozygous female with fabry disease: implications for enzyme
      replacement therapy.
AB  - We report an asymptomatic female with Fabry disease immunohistochemically
      diagnosed by renal biopsy. She was initially diagnosed as having nephrotic
      syndrome, and renal biopsy was performed for pathological diagnosis. The renal
      specimen revealed non-specific findings (minor glomerular abnormalities) for
      nephrotic syndrome. Numerous laminated bodies in glomerular epithelial cells in
      electron microscopic findings and accumulations of ceramidetrihexoside
      immunohistochemically were observed and she was diagnosed with Fabry disease.
      However, no other laboratory data or clinical findings supported the diagnosis of
      Fabry disease. Since the efficacy of recombinant human alpha-galactosidase
      replacement therapy in this disease has been reported, whether enzyme replacement
      therapy for subclinical Fabry female patients is indicated or not is an important
      issue.

PMID- 16415521
TI  - Use of microsatellite markers to detect quantitative trait loci in Yorkshire
      pigs.
AB  - To identify genetic markers associated with economic traits in pigs, 157
      microsatellite markers were examined in Yorkshire pigs. Thirty eight female
      Yorkshire pigs were initially examined and six of them were selected as
      progenitors; half were more than 1.5 standard deviations (SD) above the mean for
      average daily gain (ADG) and backfat thickness (BFT), and the remaining half were
      more than 1.5 SD below the mean. These pigs were then mated to male Duroc pigs,
      and 200 F2 pig offspring were examined for the association of specific alleles
      with ADG and BFT. To confirm the specific markers identified in the initial
      analysis, associations of significant markers with economic traits were further
      examined in 228 additional performance-tested purebred pigs. Twenty-five
      microsatellite markers were significantly associated with either ADG or BFT, and
      among these, 17 were associated with both traits. The markers with the highest
      association to ADG were also associated with BFT. Our study reveals that specific
      markers could be used to predict economic significance, and confirms several
      quantitative trait loci (QTL) identified in previous studies. However, further
      analysis with more closely-spaced microsatellite markers is required to refine
      predictive values for economic traits and positions of QTL that are reliable for
      actual phenotypic prediction.

PMID- 16415522
TI  - Expression of fibroblast growth factor 1 (FGF1) and FGF7 in mature follicles
      during the periovulatory period after GnRH in the cow.
AB  - The aim of this study was to evaluate the expression pattern of mRNA for
      fibroblast growth factor 1 (FGF1), FGF7, and their receptor variants (FGFR2IIIb)
      in time-defined follicle classes before LH surge, between LH surge and ovulation,
      and in the early corpus luteum (CL) in the cow. The ovaries were collected by
      transvaginal ovariectomy (n=5 cows/group), and the follicles (n=5, one
      follicle/cow) were classified into the following groups: before GnRH
      administration (before LH surge); 3-5 h after GnRH (during LH surge); 10 h after
      GnRH; 20 h after GnRH; 25 h after GnRH (periovulation), and early CL (Days 2-3).
      The mRNA expression was analyzed by quantitative real-time PCR (RotorGene 3000).
      The mRNA expression of FGF1 showed no significant differences in the follicle
      groups examined, but increased significantly at the early CL phase. A transient
      increase in FGF7 mRNA expression was observed 3-5 h after GnRH and again in the
      early CL phase. In contrast, the expression of FGFR2IIIb was constant throughout
      the period from the final growth of the follicle to early CL formation. The
      results of this study suggest that FGF1 and FGF7 may be involved differently in
      the process of follicle maturation and CL formation, which is strongly dependent
      on angiogenesis.

PMID- 16415523
TI  - Improvement of cumulus-free oocyte maturation in vitro and its application to
      microinsemination with primary spermatocytes in mice.
AB  - In micromanipulation experiments using immature oocytes, final ooplasmic
      maturation is often compromised because the oocytes are usually first freed from
      their nurturing cumulus cells. This study was undertaken to determine whether
      cumulus-free in vitro maturation (IVM) in mice could be improved by modifying IVM
      medium having defined components. Cumulus-free germinal vesicle (GV) stage
      oocytes were subjected to IVM in either alphaMEM medium, TYH medium, or a 1:1
      mixture of the two (termed TaM). TYH medium produced a better maturation rate
      (181/196; 92.3%) than alphaMEM (184/257; 71.6%). However, alphaMEM supported
      better embryo development to the morula/blastocyst stage than TYH following in
      vitro fertilization (93.3% vs. 76.5%) or parthenogenetic activation (82.4% vs.
      60.4%). Mitochondrial distribution in MII oocytes was diffuse following IVM in
      alphaMEM, but was aggregated with TYH. The maturation promoting factor (MPF)
      activity in MII oocytes was significantly higher in TYH than in alphaMEM
      (P<0.05). Oocytes cultured in TaM had intermediate characteristics and
      essentially resembled in vivo matured oocytes, with the mitochondrial
      distribution pattern being most typical of that condition. The highest rate of
      development from GV oocytes to full-term fetuses following in vitro fertilization
      and embryo transfer to foster mothers (23.8%) was obtained using TaM. When this
      IVM system was applied to MI oocytes injected with spermatocytes, offspring were
      first obtained without cytoplasmic replacement at MII. Thus, optimization of the
      culture medium can considerably improve the quality of cumulus-free oocyte IVM in
      mice.

PMID- 16415525
TI  - MDR1 genotype-related pharmacokinetics: fact or fiction?
AB  - Multidrug resistant transporter MDR1/P-glycoprotein, the gene product of MDR1, is
      a glycosylated membrane protein of 170 kDa, belonging to the ATP-binding cassette
      superfamily of membrane transporters. A number of various types of structurally
      unrelated drugs are substrates for MDR1, and MDR1 and other transporters are
      recognized as an important class of proteins for regulating pharmacokinetics. The
      first investigation of the effects of MDR1 genotypes on pharmacotherapy was
      reported in 2000; a silent single nucleotide polymorphism (SNP), C3435T in exon
      26, was found to be associated with the duodenal expression of MDR1, and thereby
      the plasma concentration of digoxin after oral administration. In the last 5
      years, clinical studies have been conducted around the world on the association
      of MDR1 genotype with MDR1 expression and function in tissues, and with the
      pharmacokinetics and pharmacodynamics of drugs; however, there are still
      discrepancies in the results on C3435T. In 1995, a novel concept to predict in
      vivo oral pharmacokinetic performance from data on in vivo permeability and in
      vitro solubility has been proposed, and this Biopharmaceutical Classification
      System strongly suggested that the effects of intestinal MDR1 on the intestinal
      absorption of substrates is minimal in the case of commercially available oral
      drugs, and therefore MDR1 genotypes are little associated with the
      pharmacokinetics after oral administration. This review summarizes the latest
      reports for the future individualization of pharmacotherapy based on MDR1
      genotyping, and attempts to explain discrepancies.

PMID- 16415524
TI  - Effects of experimental cryptorchidism on sperm motility and testicular
      endocrinology in adult male rats.
AB  - The effect of induced cryptorchidism on testicular function and sperm motility
      was investigated. Bilateral cryptorchidism was created surgically in adult male
      rats (treated group), and sham-operated rats were used as a control group. Five
      rats from each group were sacrificed on days 1, 3, 5, and 7 after surgery. The
      percentage of motile spermatozoa began to decrease 1 day after the operation,
      followed by an abrupt decline 3 and 5 days later in cryptorchid rats.
      Furthermore, there were significant decreases in the other sperm motility
      parameters 5 days after inducement of cryptorchidism. In cryptorchid rats, plasma
      concentrations of LH, FSH, testosterone, and inhibin B were significantly lower
      than in the control group 1 day after the operation. Thereafter, plasma
      concentrations of LH, FSH, and testosterone gradually increased in the
      cryptorchid rats. On the other hand, plasma concentrations of inhibin B showed a
      further decline from day 3 after the operation onward. Concentrations of
      immunoreactive (ir)-inhibin, but not testosterone, in testicular interstitial
      fluid were remarkably increased until 3 days after surgery in the cryptorchid
      rats, and declined thereafter. Testicular response to human chorionic
      gonadotropin (hCG) for testosterone release was decreased in the cryptorchid rats
      compared with the control rats, indicating that heat stress to testes resulted in
      a reduction of the activity of Leydig cells and Sertoli cells. These results
      clearly indicate that heat stress to the testes resulted in a significant
      reduction of sperm activity within 3 days, and this was followed by changes in
      testicular endocrine function.

PMID- 16415526
TI  - Evaluation of Bayesian predictability of vancomycin concentration using
      population pharmacokinetic parameters in pediatric patients.
AB  - The objective of this study was to evaluate the Bayesian predictability of
      vancomycin (VCM) pharmacokinetics in Japanese pediatric patients using one
      compartment population pharmacokinetic (PPK) parameters, which we reported
      previously. The validity of the PPK model was evaluated by bootstrap method and
      cross validation method, and the Bayesian predictive performance was examined.
      The predictive performance of the PPK model for premature patients was also
      examined. The cross validation method showed the predictability to be acceptable
      for practical use, especially for predicting trough concentration using other
      trough data. However, for the external premature patient data, this PPK model did
      not seem to be adequate. A theoretical approach using a simulation technique was
      also examined to evaluate the predictive performance. The results suggested that
      the predictability at the peak was not necessarily good at all sampling times and
      the predictability at the trough was better when a later time point was used. The
      optimal sampling time for prediction of VCM concentration in pediatric patients
      is discussed.

PMID- 16415527
TI  - Stereoselective effect of amiodarone on the pharmacokinetics of racemic
      carvedilol.
AB  - We investigated whether there was a stereoselective effect of amiodarone on the
      pharmacokinetics of carvedilol. Among a series of 106 inpatients with heart
      failure, 52 received carvedilol monotherapy (carvedilol group) and 54 received
      carvedilol plus amiodarone (carvedilol+amiodarone group). The serum carvedilol
      concentration administered/dose ratio was compared between the two groups based
      on HPLC measurement of the serum levels of carvedilol, amiodarone, and
      desethylamiodarone. In 6 patients from the carvedilol group, serum carvedilol
      levels were compared before and after coadministration of amiodarone. There was
      no significant between-group difference of the serum concentration to dose (C/D
      ratio) for the R-enantiomer carvedilol, however, the C/D ratio for the S
      enantiomer and the serum S-carvedilol to R-carvedilol (S/R) ratio were both
      significantly lower in the carvedilol group than in the carvedilol+amiodarone
      group(47.8+/-56.7 versus 95.3+/-105 ng/mg/kg, P=0.0048 and 0.460+/-0.207 versus
      0.879+/-0.377 ng/mg/kg, P<0.001), respectively. Furthermore, the mean S
      carvedilol concentration over 14 days of coadministration with amiodarone was
      higher than that before coadministration (6.54+/-1.73 ng/mL versus 3.03+/-0.670
      ng/mL, P<0.001). These results suggest that metabolism of S-carvedilol was
      markedly inhibited by coadministration of amiodarone.

PMID- 16415528
TI  - Prediction of absorbability of poorly water-soluble drugs based on permeability
      obtained through modified in vitro chamber method.
AB  - Permeability is an underlying parameter to control drug absorption. For highly
      water-soluble drugs, the high correlation between their permeability and fraction
      absorbed in humans is reported. In the present study, to predict the
      absorbability of poorly water-soluble drugs in humans, a new experimental method
      of the permeation study was proposed and subjected to examination. Firstly, using
      the in vitro chamber method modified to contain 5% (final concentration) dimethyl
      sulufoxide (DMSO) in both compartments of the chamber (DMSO-MS), the effect of
      DMSO on membrane integrity was evaluated. Secondly, the correlation between the
      apparent permeability coefficients (Papp) obtained through DMSO-M or DMSO-MS and
      fractions absorbed in humans were investigated using 7 poorly water-soluble
      drugs. Membrane integrity of the rat intestinal tissues was maintained after
      using DMSO-MS, as with that after using the conventional in vitro chamber method.
      Papp of two paracellular markers obtained through DMSO-MS was not different from
      that obtained through the conventional chamber method. In the permeation study of
      the P-glycoprotein substrate, Papp from both mucosal to serosal and serosal to
      mucosal sides obtained through DMSO-MS was not significantly different from that
      obtained through the conventional chamber method. The correlation between Papp
      obtained through DMSO-MS and Fa which was expressed by the equation of Fa=1-exp (
      Pappx1.38x10(5)) (r2=0.980), was more favorable than the correlation between Papp
      obtained through DMSO-M and Fa which was expressed by the equation of Fa=1-exp (
      Pappx2.12x10(5)) (r2=0.875). These results showed that DMSO-MS was a useful
      method for predicting the absorbability of poorly water-soluble drugs.

PMID- 16415529
TI  - Pharmacokinetics and biodisposition of poly(vinyl alcohol) in rats and mice.
AB  - Poly(vinyl alcohol) (PVA) of various molecular weight (MW=10,560-116,600) was
      successfully labeled with fluorescein isothiocyanate isomer I (FITC) according to
      the method of de Belder and Granath. A high-performance size-exclusion
      chromatographic procedure was developed for the quantitative analysis of FITC
      labeled poly(vinyl alcohol) (F-PVA) in biological samples. F-PVA (80 K)
      disappeared slowly from the blood circulation according to the first-order
      kinetics (t1/2=7 h) after intravenous injection to rats. A dose-independent
      behavior of F-PVA (80 K) was observed in the blood circulation, in the tissue
      distribution and in the urinary and fecal excretions. This suggested that PVAs
      are eliminated exclusively by the mechanisms that do not involve saturable
      transport processes. Furthermore, it was found that PVAs are very stable in the
      body because no degradation product was detected in the urine and feces. 125I
      labeled poly(vinyl alcohol) (125I-PVA) was prepared by introducing tyramine
      residues to the hydroxyl groups of PVA molecules by the 1,1'-cabonyldiimidazole
      (CDI) activation method. 125I-PVA (80 K) was retained in the blood circulation
      for several days after intravenous injection to mice. Although the tissue
      distribution of PVAs was small, a significant accumulation into the liver and the
      spleen was observed. Fluorescence microscopic examination of paraffin section of
      the liver revealed that F-PVA (80 K) was endocytosed by the liver parenchymal
      cells. 125I-PVA (80 K) captured by liver was slowly transported via the bile
      canaliculi and gall bladder to the intestine and excreted in the feces. It was
      suggested, therefore, a long time is necessary for 125I-PVA (80 K) to be excreted
      perfectly from the body.

PMID- 16415530
TI  - Na+/H+ exchanger 3 affects transport property of H+/oligopeptide transporter 1.
AB  - Oligopeptide transporter PEPT1 is thought to be involved in the intestinal
      absorption and renal reabsorption of peptides and therapeutic agents. The driving
      force of PEPT1 is H+ gradient, a part of which is supplied by Na+/H+ exchanger
      (NHE) expressed on the apical surface of the epithelium although molecular
      identification of NHE has not yet been fully clarified. Here we examined the
      effect of NHE3 coexpression on the function of PEPT1 to support the hypothesis
      that NHE3 regulates PEPT1 function by supplying its driving force. HEK293 cells
      expressing PEPT1 alone exhibited Na+-independent but pH-dependent uptake of
      glycylsarcosine (GlySar), whereas those coexpress PEPT1 and NHE3 showed an
      increase in GlySar uptake and conferred Na+-dependence on the uptake of GlySar.
      The increase in GlySar transport by PEPT1 depended on the expression level of
      NHE3 and was found at various levels of PEPT1 expression. Kinetic analysis of
      GlySar uptake in HEK293 cells expressing both PEPT1 and NHE3 or those expressing
      PEPT1 alone revealed an approximately 3 times increase in the transport capacity
      in the presence of NHE3, as normalized by PEPT1 mRNA expression. Confocal
      microscopy indicated that both PEPT1 and NHE3 are colocalized on the cell-surface
      of HEK293 cells. Thus, the present findings are the first to specify that NHE3
      exerts post-transcriptional stimulation of PEPT1-mediated transport and can
      affect cellular uptake of the substrates by PEPT1 expressed on apical membranes
      in the body.

PMID- 16415531
TI  - Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute
      carrier transporter superfamilies.
AB  - Pairs of forward and reverse primers and TaqMan probes specific to each of 46
      human ATP-binding cassette (ABC) transporters and 108 human solute carrier (SLC)
      transporters were prepared. The mRNA expression level of each target transporter
      was analyzed in total RNA from single and pooled specimens of various human
      tissues (adrenal gland, bone marrow, brain, colon, heart, kidney, liver, lung,
      pancreas, peripheral leukocytes, placenta, prostate, salivary gland, skeletal
      muscle, small intestine, spinal cord, spleen, stomach, testis, thymus, thyroid
      gland, trachea, and uterus) by real-time reverse transcription PCR using an ABI
      PRISM 7700 sequence detector system. In contrast to previous methods for
      analyzing the mRNA expression of single ABC and SLC genes such as Northern
      blotting, our method allowed us to perform sensitive, semiautomatic, rapid, and
      complete analysis of ABC and SLC transporters in total RNA samples. Our newly
      determined expression profiles were then used to study the gene expression in 23
      different human tissues, and tissues with high transcriptional activity for human
      ABC and SLC transporters were identified. These results are expected to be
      valuable for establishing drug transport-mediated screening systems for new
      chemical entities in new drug development and for research concerning the
      clinical diagnosis of disease.

PMID- 16415532
TI  - Localization of rat cytochrome P450 in various tissues and comparison of
      arachidonic acid metabolism by rat P450 with that by human P450 orthologs.
AB  - Metabolites of arachidonic acid produced by P450 are interesting substances with
      prominent physiological functions. To elucidate the physiological function of
      P450, it is necessary to identify a specific P450 in a particular tissue or organ
      and to characterize its catalytic activities. In this study, the expression of
      CYP2A1, 2B1, 2C23, 2J3, and 4F1 was investigated in liver, lung, kidney, spleen,
      heart, brain, and testis of rats by RT-PCR. Furthermore, arachidonic acid
      metabolism was investigated using the rat P450s described above and human CYP2A6,
      2B6, 2C9, 2C18, 2C19, 2J2, and 4F2. Among the rat P450s, CYP2B1 and 2C23
      efficiently produced EETs and CYP4F1 produced 19/20-HETE in abundace. CYP2B1 was
      specifically expressed in the lung. CYP2C23 was detected in all tissues used in
      this study. CYP4F1 was expressed in the kidney as well as in the liver. Among the
      human P450s, CYP2C9 and 2C19 efficiently produced EETs. CYP4F2 produced 19/20
      HETE. The catalytic properties of rat CYP2C23 were similar to those of human
      CYP2C9 and 2C19. The catalytic properties of CYP4F isoforms were also similar
      between humans and rats. A systematic analysis of P450 expression in various
      tissues and of its catalytic property may provide valuable information on the
      physiological roles of P450s in each tissue.

PMID- 16415533
TI  - Pharmacokinetics of fluconazole and fosfluconazole after intraperitoneal
      administration to peritoneal dialysis rats.
AB  - Fluconazole (FLCZ) is an antifungal agent that is efficacious in the treatment of
      fungal peritonitis. Fosfluconazole (F-FLCZ) is the phosphate prodrug of FLCZ,
      which is highly soluble compared with FLCZ. F-FLCZ is useful against fungal
      peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients because
      it has a high water solubility. The aims of the present study were to
      characterize the peritoneal permeability of FLCZ and the pharmacokinetics of FLCZ
      and F-FLCZ after intraperitoneal (i.p.) administration to peritoneal dialysis
      rats. FLCZ or F-FLCZ was administered intravenously and intraperitoneally. After
      the i.p. administration of F-FLCZ, FLCZ was detected in circulating blood and the
      dialyzing fluid in peritoneal dialysis rats. The concentration of plasma FLCZ
      after the i.p. F-FLCZ administration was lower than that after the intravenous
      (i.v.) F-FLCZ administration. It is considered that the dose should be increased
      appropriately when F-FLCZ is administered intraperitoneally. The profiles of
      plasma FLCZ after i.v. and i.p. administrations were analyzed using a two
      compartment model in which the distribution volume of the peripheral compartment
      was fixed at a volume of the dialyzing fluid (peritoneal dialysis PK model). The
      peritoneal dialysis PK model could describe the profiles of plasma and dialyzing
      fluid FLCZ. These results suggest that FLCZ and F-FLCZ could be administered
      intraperitoneally for the treatment of fungal peritonitis in CAPD patients.

PMID- 16415534
TI  - Carrier-mediated uptake of grepafloxacin, a fluoroquinolone antibiotic, by the
      isolated rat lung cells.
AB  - Grepafloxacin (GPFX) is a new quinolone antibiotic (NQ) which is highly
      distributed to the lung and other tissues. In the present study, to characterize
      the distribution mechanism of GPFX to the lung, the uptake of GPFX by isolated
      rat lung cells was examined in vitro. GPFX was rapidly taken up by the cells, and
      the uptake reached a steady-state within 5 min. The cell-to-medium concentration
      ratio at equilibrium was 56.8+/-1.9 microL/mg protein, which was much higher than
      the cellular volume. GPFX uptake consisted of a saturable component (Km: 264+/
      181 microM, Vmax: 2.94+/-2.33 nmol/min/mg protein) and a nonsaturable component
      (Pdif: 7.04+/-2.17 microL/min/mg protein). The uptake of GPFX was reduced in the
      presence of ATP-depletors (FCCP and Rotenone) and by the replacement of sodium
      with choline in the medium, suggesting that GPFX uptake is at least partially
      mediated by an Na+- and energy-dependent process. GPFX uptake tended to be
      reduced in the presence of other NQs such as levofloxacin, lomefloxacin and
      sparfloxacin, but was only minimally affected by the substrates of several uptake
      mechanisms already identified in the liver and kidney such as taurocholate, p
      aminohippurate, L-carnitine and tetraethylammonium. These results suggested that
      GPFX is taken up by the lung partially via carrier-mediated transport system(s),
      distinct from the identified transporters, and such active transport systems may
      at least partially account for the efficient distribution of GPFX to the lung.

PMID- 16415535
TI  - Molecular dissection of ARP1 regions required for nuclear migration and cell wall
      integrity checkpoint functions in Saccharomyces cerevisiae.
AB  - The dynactin complex is one of the components required for the regulation of the
      cell wall integrity checkpoint, which ensures the completion of cell wall
      remodeling before mitosis. The core of the dynactin complex is a backbone
      filament composed of monomers of an actin-related protein, Arp1, which is also
      involved in nuclear migration. To examine the molecular basis for the dual
      functions of the dynactin core subunit Arp1p in yeast, we constructed 32 mutated
      arp1 alleles. We assessed the effects of the mutations on cell wall integrity
      checkpoint and nuclear migration functions and identified four categories of
      mutants: 1) those showing no change from the wild type; 2) those resulting in a
      defective cell wall integrity checkpoint but normal nuclear migration; 3) those
      with a normal cell wall integrity checkpoint but defective nuclear migration; and
      4) those defective in both the cell wall integrity checkpoint and nuclear
      migration functions. Our results show a separation of the two functions in the
      molecular structure of Arp1p and indicate that a local surface region of Arp1p is
      important in maintaining the cell wall integrity checkpoint function.

PMID- 16415536
TI  - Remember typhoid fever as a cause of acute nephritic syndrome even in Japan.

PMID- 16415537
TI  - Cholesterol embolization syndrome: how to recognize and prevent this potentially
      catastrophic iatrogenic disease.

PMID- 16415538
TI  - "Cocktail" antihypertensive chronotherapy for perfect control of morning
      hypertension in diabetic patients.

PMID- 16415539
TI  - Dehydroepiandrosterone sulfate (DHEAS) therapy for myotonic dystrophy type 1 and
      myotonia.

PMID- 16415540
TI  - Autoimmune pancreatitis.
AB  - Although the pathogenesis of autoimmune pancreatitis is unclear, recent evidence
      of clinical aspects are presented: (i) mild abdominal symptoms, usually without
      acute attacks of pancreatitis; (ii) occasional existence of obstructive jaundice;
      (iii) increased levels of serum gammaglobulin, IgG or IgG4; (iv) presence of
      autoantibodies; (v) diffuse enlargement of the pancreas; (vi) irregularly
      narrowing of the pancreatic duct (sclerosing pancreatitis) with often intra
      pancreatic biliary stenosis or coexistence of biliary lesions (sclerosing
      cholangitis similar to primary sclerosing cholangitis: PSC) on endoscopic
      retrograde cholangiopancreatographic (ERCP) images; (vii) fibrotic changes with
      lymphocyte and IgG4-positive plasmacyte infiltration, and obliterative thrombo
      phlebitis; (viii) occasional association with other systemic lesions such as
      sialoadenitis, retroperitoneal fibrosis, interstitial renal tubular disorders,
      and (ix) effective steroid therapy. In addition to pancreatic and extra
      pancreatic lesions, diabetes mellitus is occasionally responsive to steroid
      therapy. Further studies are needed to clarify the pathogenesis.

PMID- 16415541
TI  - The Brugada syndrome--an update.
AB  - Brugada syndrome is characterized by ST-segment elevation in the right precordial
      leads (V1-V3) and an episode of ventricular fibrillation (VF) in the absence of
      structural heart disease. A number of reports from the world have unveiled the
      clinical, electrocardiographic, electrophysiologic and prognostic features of
      Brugada syndrome, and two recent consensus reports have suggested the diagnostic
      criteria of Brugada syndrome and the risk stratification for the identification
      of high risk Brugada patients for sudden cardiac death. SCN5A, the gene encoding
      the alpha subunit of the sodium channel, is the only gene thus far linked to
      Brugada syndrome; its prognostic value remains unclear. On the other hand,
      advances in the understanding of the cellular mechanism for Brugada phenotype
      derived from experimental studies have suggested possibilities for the
      development of strategies for managing and treating patients with Brugada
      syndrome. In this review, the recent understanding and knowledge of Brugada
      syndrome will be updated.

PMID- 16415542
TI  - Metabolic syndrome amplifies the LDL-cholesterol associated increases in carotid
      atherosclerosis.
AB  - OBJECTIVE: Carotid intima-media thickness (IMT) is a useful surrogate marker of
      cardiovascular disease. In addition to low-density lipoprotein cholesterol (LDL
      C), metabolic syndrome has been linked to the pathogenesis of atherosclerosis.
      The present study investigated whether the clustering of multiple components of
      metabolic syndrome has a greater impact on vascular parameters than individual
      components of metabolic syndrome, and assessed the association between carotid
      IMT and LDL-C and metabolic syndrome. METHODS: Carotid IMT was evaluated on B
      mode ultrasonography in 760 patients (340 men aged 64+/-16 years and 420 women
      aged 69+/-13 years) in the Medical Department of Seiyo Municipal Nomura Hospital.
      The subjects did not demonstrate any clinical signs of cardiovascular disease. We
      investigated the association between carotid IMT and confounding risk factors
      including LDL-C and metabolic syndrome using the 2005 Japanese criteria. RESULTS:
      Carotid IMT increased with increasing numbers of metabolic syndrome components (p
      for trend<0.001). Multiple regression models, including age, sex, body mass
      index, smoking status, LDL-C, diabetes mellitus as well as each individual
      component of metabolic syndrome as continuous variables, showed that both
      metabolic syndrome (beta=0.100; p=0.029) and LDL-C (beta=0.210, p<0.001) were
      independent determinants of carotid IMT. Metabolic syndrome amplified the LDL-C
      associated increases in carotid atherosclerosis. CONCLUSIONS: Even after taking
      into account each individual component of MS, the clustering of visceral obesity
      with at least 2 of the 3 components, and LDL-C are independently associated with
      increased carotid IMT. This suggests that the components of metabolic syndrome
      interact to synergistically impact vascular thickness.

PMID- 16415544
TI  - The effect of dehydroepiandrosterone sulfate (DHEAS) on myotonia: intracellular
      studies.
AB  - OBJECTIVE: In order to find some appropriate medicine to suppress myotonia
      without decreasing muscle strength experiments were performed on myotonic (mto)
      mice whose Cl channel does not develop due to stop codon and serves as an animal
      model of myotonia. In myotonic dystrophy dehydroepiandrosterone is low in the
      serum and it has been reported that intravenous injections of DHEAS to human
      cases improves myotonia and activities of daily living. MATERIALS AND METHODS:
      Three pairs of heterozygote mto mice, SWR/J-Clcn1(adr-mto/+) and ten Wistar rats
      were used. We performed intracellular recordings of myotonia from mto mice and
      the drug effects on insertion myotonia were recorded from the hemidiaphragm
      preparations of mto mice with different concentrations of DHEAS. Isometric twitch
      tension was recorded from rat hemidiaphragm preparations in Tyrode's solution and
      the effect of DHEAS on the muscle twitch tension was measured at different
      concentrations of DHEAS from 100 mg/l to 300 mg/l. The effect of mexiletine on
      ITT was also measured. RESULTS: In mto mice insertion myotonia was recorded as
      soon as the microelectrode was inserted in the muscle cells. When DHEAS was added
      to Tyrode's solution, insertion myotonia was suppressed. DHEAS decreased ITT up
      to 70% of the original value, though mexiletine decreased ITT to 30% of the
      original value. Therefore, the decrement of the muscle strength in DHEAS solution
      is much smaller than that of mexiletine. CONCLUSION: Since myotonic dystrophy
      shows progressive muscle weakness in addition to myotonia, medications like DHEAS
      are more favorable than the typical Na channel blocker.

PMID- 16415543
TI  - Morning blood pressure predicts hypertensive organ damage in patients with renal
      diseases: effect of intensive antihypertensive therapy in patients with diabetic
      nephropathy.
AB  - Blood pressure (BP) measured at home early in the morning (HBP) has been
      recognized as a useful predictor for organ damage and has been viewed as an
      important therapeutic target in patients with hypertension. The present study was
      aimed to determine whether this notion holds true in patients with progressive
      renal disease. The study enrolled patients with mild to moderate renal
      impairment. They were all directed to record self-measured HBP to evaluate the
      adequacy of BP control. In addition to the conventional antihypertensive therapy,
      intensive treatment to more efficiently reduce elevated morning HBP was applied,
      especially in patients with diabetic nephropathy. The results were as follows: 1)
      The status of BP control assessed using HBP and office/clinic BP (OBP) shows
      predominance of morning hypertension. The prevalence of patients with well
      controlled systolic HBP was 38%, those with poorly-controlled HBP 30%, masked
      hypertension 20% and white coat hypertension 12%. 2) Early morning systolic HBP
      in diabetics was significantly higher than that in non-diabetics. However, when
      evaluated on systolic OBP, both groups were comparable.3)Logistic regression
      analysis showed that the predictive variables to explain morning hypertension
      (more than 130 mmHg and increased systolic HBP) were age, amount of daily urinary
      protein excretion and left ventricular mass index (LVMI).4)Following conventional
      therapy, intensive antihypertensive therapy consisting of calcium channel
      blockers (CCB) and/or diuretics given in the morning, and angiotensin receptor
      blockers (ARB) given in the evening, together with alpha1-blockers given at
      bedtime, efficaciously reduced elevated HBP in the morning. This result was
      associated with significant reduction in daily urinary protein excretion and in
      serum plasminogen-activator inhibitor (PAI-1) concentration. The present study
      indicates that, regardless of ongoing conventional antihypertensive therapy, the
      majority of patients with renal disease had morning hypertension, suggesting that
      these patients are at a higher risk for cardiovascular disease. For the purpose
      of improving morning hypertension, intensive treatments with combined CCB, ARB
      and alpha1-blockers could have substantial benefit on the morbidity and prognosis
      in patients with diabetic nephropathy.

PMID- 16415545
TI  - Clinical characteristics of first-ever atherothrombotic infarction or lacunar
      infarction with hyperlipidemia (J-STARS-C): an analysis of data from the stroke
      data bank of Japan.
AB  - OBJECTIVE: The clinical trial, Japan Statin Treatment Against Recurrent Stroke (J
      STARS), is being carried out to investigate the efficacy of statin treatment
      against recurrent stroke. To participate in J-STARS, patients must have a past
      history of ischemic stroke excluding cardioembolic events, and must be clinically
      diagnosed with hyperlipidemia (HL). Before starting J-STARS, we needed to be
      aware of the clinical characteristics of the patients who were eligible to
      participate in this study. METHODS: Between 1999 and 2002, 7,149 patients with
      ischemic stroke were enrolled in a stroke data bank developed by the Japan
      Standard Stroke Registry Study Group. From this, we acquired the data on 1,487
      patients with first-ever atherothrombotic infarction (ATI) or lacunar infarction
      (LI) with a satisfactory functional outcome on discharge. RESULTS: Patients with
      HL were significantly younger (65.3+/-11.0 vs 68.4+/-10.9, p<0.0001) and showed a
      higher frequency of concomitant hypertension (70.9% vs 61.0%, p=0.0002), diabetes
      mellitus (42.2% vs 25.7%, p<0.0001) or both (31.7% vs 16.4%, p<0.0001) compared
      to those without HL. The ratio of ATI to LI and the frequency of prior ischemic
      heart disease (IHD) did not differ between the 2 groups. Among 467 patients with
      HL, 52.7% did not receive treatment on admission. CONCLUSION: ATI or LI patients
      with HL had an earlier age of onset and higher frequency of other lifestyle
      related diseases, and this probably includes many with metabolic syndrome,
      whereas the frequency of IHD was not different between these 2 groups.

PMID- 16415546
TI  - Treatment of chronic fatigue syndrome with antibiotics: pilot study assessing the
      involvement of Coxiella burnetii infection.
AB  - OBJECTIVE: To examine whether Coxiella burnetii (C. burnetii) is involved in
      chronic fatigue syndrome (CFS), we administered tetracycline antibiotics to
      subjects with CFS, and followed changes in clinical symptoms, PCR findings, and
      C. burnetii antibody titers. PATIENTS AND METHODS: The subjects were 8 patients
      with CFS and 213 with nonspecific complaints such as chronic fatigue and low
      grade fever for several months or longer but not meeting the diagnostic criteria
      for CFS. All were examined for C. burnetii infection by nested PCR and the
      indirect immunofluorescence test (IF). RESULTS: Four CFS patients (the CFS group)
      and 54 controls [the post-Q fever fatigue syndrome (QFS) group] positive for C.
      burnetii were treated mainly with minocycline or doxycycline (100 mg/day) for 3
      months. After treatment, all 58 patients tested negative for C. burnetii
      infection. In the CFS group, no significant difference was noted between the mean
      pre- and post-treatment temperatures or headache scores. Similarly, there was no
      significant improvement in performance status (PS) scores. In the QFS group,
      however, mean temperatures and headache scores were significantly decreased after
      treatment (p<0.001). PS scores were also improved. CONCLUSION: These results
      suggest the possibility of direct involvement of C. burnetii in the pathological
      state of CFS to be low, despite the C. burnetii infection rate being high in CFS
      patients. This is a pilot study and further larger investigations are necessary
      to confirm our preliminary results.

PMID- 16415547
TI  - Progressive facilitation of antegrade conduction via an accessory pathway in a
      patient with Wolff-Parkinson-White syndrome and permanent atrial fibrillation.
AB  - The case of a 64-year-old man with Wolff-Parkinson-White syndrome and permanent
      atrial fibrillation (AF) is reported. The patient was admitted due to
      electrocardiographic feature of AF with rapid conduction over the left-sided
      accessory pathway. Administration of pirmenol effectively suppressed the
      ventricular response via an accessory pathway. A transesophageal echocardiography
      detected an uncertain thrombus in the left atrial appendage. During the 33-month
      follow-up period, the ventricular response via an accessory pathway was
      progressively facilitated. Radiofrequency catheter ablation using a transseptal
      approach was performed during AF, resulting in complete elimination of the
      antegrade accessory pathway conduction.

PMID- 16415548
TI  - Multiple bone fractures found in a young sarcoidosis patient with long stable
      disease.
AB  - A 22-year-old Japanese man was found to have bilateral hilar lymphadenopathy
      (BHL), and was diagnosed with sarcoidosis in 1995. He was followed without
      treatment until 2002, when a bone fracture due to osseous sarcoidosis was found
      in his left thumb. Despite systemic treatment with corticosteroid and
      methotrexate, a new bone lesion developed in his right foot and his right middle
      finger was fractured. The patient also suffered multiple organ involvements
      including brain and muscle lesions. This is the first report of a sarcoidosis
      patient who presented with BHL, and developed bone fractures after a long stable
      period of more than 5 years.

PMID- 16415549
TI  - Inhaled corticosteroid rapidly improved pulmonary sarcoidosis.
AB  - We report two cases in whom inhaled corticosteroid rapidly improved pulmonary
      sarcoidosis. In the first case, fluticasone at 400 microg/day was initiated,
      because dry cough and small nodular shadows on chest X-ray persisted for six
      months. But her cough and the nodular shadows were persisted, therefore the
      treatment was replaced with budesonide at 800 microg/day. Two months later, her
      dry cough subsided and pulmonary shadows improved. Serum angiotensin-converting
      enzyme (ACE) level was decreased and pulmonary function improved. In the second
      case, bumethasone was already administered at a local clinic. Budesonide at 400
      microg/day was combined with oral steroid, because pulmonary shadows continued
      for eight years. Also two months later, the serum ACE level was decreased and the
      pulmonary shadows slightly improved. Inhaled corticosteroid therapy for two to
      three months is tolerable, and may be a useful treatment option in some patients
      with sarcoidosis.

PMID- 16415551
TI  - A variant form of nasogastric tube syndrome.
AB  - Nasogastric tube syndrome named by Sofferman et al in 1981 is a laryngeal
      complication presenting with life-threatening vocal cord abductor paralysis
      derived from peroforation of the NG tube-induced esophageal ulcer. As compared
      with the previously reported cases of this syndrome, our 4 autopsied patients
      were so peculiar in the following two points that vocal cord abductor paralysis
      developed repeatedly and no esophageal ulcer was present in spite of the presence
      of the laryngeal abductor muscle injury. We hypothesized that the etiology of
      such a variant form was circulatory injury of the laryngeal abductor muscle which
      was caused by the compression of the postcricoid blood vessels perfusing this
      muscle. Nasogastric tube syndrome, which is treatable by decannulation, cannot be
      ruled out even if no esophageal ulcer is detected by fiberoptic laryngoscopy.

PMID- 16415550
TI  - Two cases of hemiballism-hemichorea with T1-weighted MR image hyperintensities.
AB  - Two cases of hemiballism-hemichorea have been reported in woman patients with
      hyperglycemia; this was a feature of striatal hyperintensity on the T1-weighted
      MRI. In the first case, strict management of diabetes and treatment with pimozide
      effectively suppressed the movement disorder. The Z-score Imaging System revealed
      hyperperfusion in the bilateral dentate nuclei, left striatum, and bilateral
      motor cortices. In the second case, painful hemiballism-hemichorea limb, followed
      by the upper limb. The severity of HB-HC corresponded to the expansion of the
      striatal lesion. The mechanism of HB-HC by using statistical cerebral blood flow
      evaluation has also been discussed.

PMID- 16415552
TI  - Encephalopathy with isolated reversible splenial lesion of the corpus callosum.
AB  - We report a 51-year-old Japanese man with chronic alcoholism who complained of
      mental confusion following respiratory and intestinal infections. The splenium of
      the corpus callosum showed hyperintensity on both diffusion-weighted MR images
      and fluid-attenuated inversion recovery images and hypointensity on T1-weighted
      images. These findings were resolved on MR images obtained 3 days later. He
      showed complete neurological recovery within 2 months. We suspected that he had
      mild encephalopathy with a reversible splenial lesion after systemic viral or
      bacterial infection.

PMID- 16415553
TI  - Lateropulsion due to a lesion of the dorsal spinocerebellar tract.
AB  - We report three cases showing body lateropulsion as the sole or predominant
      symptom of caudal lateral medullary infarction. All of them presented a small
      infarction on the lateral surface of the caudal medulla corresponding to the
      dorsal spinocerebellar tract (DSCT). Disturbed unconscious proprioception of the
      lower trunk and the lower limb conveyed by the DSCT might have been responsible
      for the isolated lateropulsion. Although lateropulsion itself improved within two
      weeks, one patient's condition progressed to typical lateral medullary
      infarction. Lateropulsion caused by DSCT infarction could be a prodromal symptom
      of perfusion failure of a vertebral artery or the posterior inferior cerebellar
      artery.

PMID- 16415555
TI  - Clubbed fingers in a patient with inflammatory gingival hyperplasia.
AB  - The association of clubbing with miscellaneous diseases and its diagnostic
      implications are such that its detection should prompt consideration of the
      underlying etiology. We encountered a 48-year-old woman with clubbed fingers and
      a cauliflower-like gingival swelling on the hard palate of the upper jaw. There
      were no conventionally well-known causes for clubbing. Histological examination
      of gum biopsy specimen revealed a diagnosis of inflammatory gingival hyperplasia.
      As an etiology of clubbed fingers, gingivitis was suggested, since clubbing was
      regressed in parallel with remission of the gingivitis after the treatment by
      extraction of anterior teeth. Possible involvement of an autoimmune process in
      the pathogenesis was also considered, because of concomitant elevation of serum
      anti-double strand DNA antibodies. We recommend examination of the oral cavity
      for search of an inflammatory disease in cases with clubbed fingers, particularly
      when other common causes are not apparent.

PMID- 16415554
TI  - Two cases of systemic lupus erythematosus complicated with colonic ulcers.
AB  - We report two cases of systemic lupus erythematosus (SLE) complicated with
      colonic ulcerations. One patient was successfully cured by steroid therapy, while
      the other did not respond to steroid but oral mesalazine was effective. Systemic
      lupus erythematosus is frequently accompanied by gastrointestinal symptoms, but
      colonic lesions are quite rare, and the regular treatment is not fixed yet. The
      high-dose steroidal regimen may be effective for microvasculitis, although it may
      increase the risk of perforated ulcer of the intestinal tract, which is a life
      threatening complication. Further analysis of its outcomes, and establishment of
      the regular guideline for its treatment are expected.

PMID- 16415556
TI  - Autoimmune hemolytic anemia in an elderly patient with primary Sjogren's
      syndrome.
AB  - Primary Sjogren's syndrome is an autoimmune disease characterized by lymphocytic
      infiltration of the salivary glands and lacrimal glands. The histological
      features of chronic inflammation in primary Sjogren's syndrome may be associated
      with B cell hyper-reactivity. This syndrome also has various manifestations
      associated with other exocrine glands and nonglandular tissues. The hematological
      abnormalities usually seen in Sjogren's syndrome are lymphopenia, leucopenia, and
      thrombocytopenia. Although the direct Coomb's test is often positive, the
      occurrence of autoimmune hemolytic anemia (AIHA) is rare. Here, we report an
      elderly patient with primary Sjogren's syndrome who developed AIHA during the
      clinical course.

PMID- 16415557
TI  - Sepsis caused by food-borne infection with Escherichia coli.
AB  - We report a case of sepsis caused by Escherichia coli (E. coli) of serotype O
      143. A 78-year-old man developed symptoms of gastroenteritis after ingesting raw
      meat on noodles. He rapidly developed respiratory failure. Blood culture grew E.
      coli. The sepsis seemed to have directly spread from a food-borne infection. The
      development of primary sepsis after ingesting E. coli is very rare. We suspect
      that bacterial translocation played a major role. Serotype O-143 is recognized in
      enteroinvasive E. coli (EIEC) as well as in Shigella dysenteriae. The pathogen in
      the present case is suspected of being EIEC although the isolated E. coli strain
      was negative for the inv and ipa genes.

PMID- 16415558
TI  - Carotid ultrasonographic appearance of the rupture of an unstable atheromatous
      plaque in a patient with acute ischemic stroke.

PMID- 16415559
TI  - Effect of metal halide light source on hardness, water sorption and solubility of
      indirect composite material.
AB  - This study evaluates the effects of a metal halide light source on the post
      polymerization properties of the Sinfony indirect composite material. Two
      polymerization systems were employed: the Hyper LII system, comprising a metal
      halide polymerization unit, and the Visio system, comprising two proprietary
      units designed for polymerizing the Sinfony composite. The composite material was
      polymerized for 60, 120 or 180 s with the LII system. As a control, the composite
      was polymerized for 15 min with the Visio system. Knoop hardness, water sorption
      and solubility were determined. The results were analyzed by Dunnett's T3
      multiple comparison test (P<0.05). Knoop hardness was greater for polymerization
      with the LII unit than for that with the Visio system. Water sorption was greater
      for polymerization with the Visio system than that with the LII unit. For
      polymerization with the LII unit for 180 s, solubility was significantly reduced
      as compared with the Visio system. Within the limitations of the current
      experiment, it can be concluded that the metal halide unit exhibited better
      polymerizing performance for the composite material than the proprietary units.

PMID- 16415560
TI  - Effect of metal conditioners on polymerization behavior of bonding agents.
AB  - This study aimed to determine the influence of metal conditioners on the
      polymerization behavior of bonding agents. Bonding agents of two-step self
      etching primer systems and metal conditioners for adhesion of dental metal alloys
      were used. Double bond conversion was determined by Fourier transform-ation
      infrared spectroscopy. The percentage of residual double bonds, including pendant
      and monomeric double bonds, was calculated by comparing the obtained ratio with
      that of the uncured bonding agent. The degree of conversion of the bonding agents
      was obtained by subtracting the remaining double bonds from 100%. ANOVA followed
      by a Tukey HDS test was performed. Degree of conversion of the bonding agents
      ranged from 86.0 to 87.8%. When the bonding agents were mixed with metal
      conditioners or solvents of the metal conditioners, double bond conversion of the
      bonding agents tended to decrease. Within the limitations of this study, which
      was far removed from clinical situations, the presence of metal conditioners and
      remaining solvents had adverse effects on the polymerization reaction of bonding
      agents. Clinicians should be cognizant of the various factors that can influence
      bond strength of restorative resins to dentin.

PMID- 16415561
TI  - Establishment of immortalized clonal cells derived from periodontal ligament
      cells by induction of the hTERT gene.
AB  - Since the periodontal ligament (PDL) contains a heterogeneous cell population, it
      is challenging to identify all cell types within the tissue and to determine
      whether they function alone to produce tissue components or interact with other
      cell types. Further, it is difficult to isolate and expand single cell clones
      from PDL cells, as normal cells have a limited life span and are phenotypically
      unstable. In the present study, we inserted the human telomerase reverse
      transcriptase (hTERT) gene, which encodes the catalytic subunit of the telomerase
      holoenzyme, into normal human periodontal ligament (HPL) cells and successfully
      obtained single cell clones. Expression of the inserted gene and telomerase
      activity in each of the clones was confirmed. Unlike the original HPL cells, at
      the end of the study (day 120), clone populations continued to actively double
      without phenotypic alteration. Osteogenic characteristics were present in some
      but not all clones. In conclusion, immortalization of HPL cells was successfully
      accomplished by transduction with the hTERT gene. This is the first report of
      immortalization of different cell types derived from PDL.

PMID- 16415562
TI  - Effects of alpha-methyl-p-tyrosine on extracellular dopamine levels in the
      nucleus accumbens and the dorsal striatum of freely moving rats.
AB  - Alpha-methyl-p-tyrosine (AMPT) is known to inhibit the formation of dopamine (DA)
      in the cytosol of dopaminergic neurons and is therefore used to study the role of
      the cytosolic DA pools. AMPT is usually administered systemically. In the present
      study, however, the effects of locally infused AMPT on the efflux of DA from the
      nucleus accumbens and dorsal striatum were analyzed, using in vivo brain
      microdialysis in unanesthetized rats. The administration of AMPT (100 microM, 4
      h) into the nucleus accumbens reduced accumbal DA output to 30% of its baseline
      level. When it was infused into the dorsal striatum, however, it reduced striatal
      DA output to 60% of its baseline level. At first sight, these data suggest that
      the amount of DA available from the AMPT-sensitive pool is larger in the nucleus
      accumbens than in the striatum. However, this cannot be the case, as the decrease
      in accumbal and striatal DA efflux induced by systemic administration of AMPT
      (250 mg/kg given intra-peritoneally) was identical. These results show that local
      infusion of AMPT is a valuable tool for analyzing the role of AMPT-sensitive
      pools within a particular brain area, but it cannot be used to compare effects
      across different brain structures because a fixed dose of AMPT differentially
      affected the nucleus accumbens and the dorsal striatum.

PMID- 16415563
TI  - Gene expression profiling and characterization under hemin limitation in
      Porphyromonas gingivalis.
AB  - Hemin is an important nutrient for Porphyromonas gingivalis growth and
      pathogenicity. We examined the gene expression profile of P. gingivalis,
      including genes involved in its pathogenicity, at various growth stages under
      hemin-standard and limited conditions by using a custom-made microarray. The
      transcription of many genes decreased after late-log and mid-log phases under
      hemin-standard and limited conditions, respectively. We focused on two groups of
      genes while comparing gene expression profiles under hemin-standard and limited
      conditions by gene tree analysis. Genes belonging to group A maintained high
      transcriptional levels, whereas genes in group B were expressed at low levels
      under standard hemin conditions. However, group B genes increased remarkably
      under hemin-limited conditions. Groups A and B contained genes involved in
      regulatory functions and protein fate, respectively. Genes related to energy
      metabolism, transport, and protein binding were present in both groups. Our
      results suggest that P. gingivalis experienced severe stress under hemin-limited
      conditions, and growth phase-dependent changes in transcription levels were
      observed for many genes. Moreover, increased expression of genes involved in
      energy metabolism suggests that hemin is related not only to pathogenicity, but
      also energy metabolism.

PMID- 16415564
TI  - Autoregulatory mechanism of Runx2 through the expression of transcription factors
      and bone matrix proteins in multipotential mesenchymal cell line, ROB-C26.
AB  - Runx2 is essential for osteoblast differentiation and gene expression of bone
      matrix proteins, however, little is known about the mechanism regulating its
      activity. In this study, the role of Runx2 on gene expression of transcription
      factors, AJ18, Msx2, and Dlx5, was examined in vitro. It is known that AJ18 and
      Msx2 act as repressors to inhibit activity of Runx2, whereas Dlx5 promotes its
      activity. An expression vector inserted Runx2 cDNA was transiently overexpressed
      in a rat multipotential mesenchymal cell line, ROB-C26 (C26). Real time reverse
      transcription-PCR analysis showed that, in exogenous Runx2-overexpressing C26
      cells (C26-Rx), AJ18 expression increased 1.8-fold, Msx2 expression increased 3.0
      fold, and Dlx5 expression increased 2.7-fold compared to the cells transfected
      with vector alone (C26-Co). Luciferase assay also showed that, in C26-Rx, AJ18
      promoter activity increased 2.1-fold compared to C26-Co. Furthermore, gene
      expression of alkaline phosphatase (ALP) and bone matrix proteins including type
      I collagen (Col1), osteocalcin (OC), osteopontin (OPN), and matrix Gla protein
      (MGP) was examined. In C26-Rx, MGP expression increased 1.8-fold, and OPN
      expression increased 1.4-fold compared to C26-Co. However, no significant
      difference in Col1, ALP, and OC expressions was detected between C26-Rx and C26
      Co. These results suggest that the existence of autoregulatory feed back loops,
      which inhibit Runx2 activity through the interaction of AJ18, Dlx5, and Msx2
      cooperating with that of MGP and OPN, interferes with the differentiation of C26
      cells toward mature osteoblasts.

PMID- 16415566
TI  - Unusual cyst-like lesions in the parapharyngeal space associated with recurrence
      of tongue carcinoma.
AB  - A 54-year-old male presented with the complaint of a painful sore on the left
      side of his tongue. Our examination found an ulcer 15 x 20 mm in size on the left
      edge of the tongue, with peripheral indurations. The lesion was diagnosed
      histopathologically as squamous cell carcinoma (T2N0M0). Consequently, the lesion
      was surgical removed and radical neck dissection was performed. Four months after
      the operation, two unusual cyst-like lesions were identified in the
      parapharyngeal space by CT and MRI. A biopsy specimen revealed recurrent
      carcinoma with a cyst-like structure. The route of the tumor metastasis into the
      parapharyngeal space was obscured, but it was speculated that the excessive lymph
      accumulation was due to a lymphatic occlusion caused by the surgical procedure,
      proliferation of the metastatic carcinoma, or stagnation and accumulation of
      tissue fluid caused by parapharyngeal invasion by the recurrent lesion.

PMID- 16415565
TI  - Effects of the enamel matrix derivative and beta-tricalcium phosphate on bone
      augmentation within a titanium cap in rabbit calvarium.
AB  - In vitro studies suggest that enamel matrix derivative (EMD) affects the early
      stages of osteogenic maturation by stimulating bone cell proliferation. In the
      present study, we evaluated the effects of EMD and beta-tricalcium phosphate
      (beta-TCP) on bone augmentation within a titanium cap in rabbit calvaria, using
      14 adult male Japanese white rabbits. The calvarium was exposed, a circular
      groove prepared, the marrow penetrated, and a standard hemispherical titanium cap
      placed in the groove. The cap was filled with a mixture of beta-TCP and EMD at
      the experimental site, and was filled with beta-TCP alone at the control site. At
      1 and 3 months after cap implantation, animals were euthanized, and histological
      sections prepared. The sections were stained with basic fuchsin and methylene
      blue, and were examined using light microscopy. At 1 month, EMD tended to
      increase the amount of bone, but there was no significant difference in the
      amount of new tissue and mineralized bone between the experimental and control
      sites. The present findings indicate that the present mixture of EMD and beta-TCP
      does not accelerate bone formation, compared with beta-TCP alone.

PMID- 16415567
TI  - Tumor necrosis factor-alpha induces apoptosis in cultured porcine luteal cells.
AB  - Some studies in mammalian species recently demonstrated that tumor necrosis
      factor (TNF)-alpha plays an important role for corpus luteum (CL) function by way
      of apoptosis during the estrous cycle. The objectives of this study were to
      clarify the induction of apoptosis in cultured porcine luteal cells by TNF-alpha
      treatment. Luteal cells prepared from porcine ovaries collected from crossbred
      mature gilts on Days 10-14 of the estrous cycle were isolated and examined as
      follows: 1) Flow cytometric analysis was carried out to determine apoptosis in
      cultured luteal cells. 2) Single-cell gel electrophoresis (comet assay) was
      performed to investigate apoptotic DNA fragmentation in luteal cells. The results
      of the flow cytometric analysis and comet assay demonstrated coincidentally that
      TNF-alpha induces DNA fragmentation in luteal cells causing apoptosis. These
      results revealed that TNF-alpha is an inducing factor of apoptosis in luteal
      cells.

PMID- 16415568
TI  - Tonic activation of brain GnRH immunoreactivity despite reduction of peripheral
      reproductive parameters in opportunistically breeding zebra finches.
AB  - Opportunistically breeding species offer the unique opportunity to understand
      mechanisms in reproductive physiology that allow for extreme flexibility in the
      regulation of reproduction. We studied a well-known opportunistic breeder, the
      zebra finch (Taeniopygia guttata) to test the hypothesis that the reproductive
      axis of opportunists is in a constant state of 'near-readiness'. In wild zebra
      finches, reproduction is highly correlated with rainfall, and in the laboratory,
      water availability and humidity are the strongest cues to affect reproductive
      activation. We therefore subjected individuals to water restriction for eleven
      weeks followed by a two week period of ad libitum access to water. The control
      group had water freely available for the entire experiment. We measured the state
      of activation of the hypothalamo-pituitary gonad (HPG) axis at three levels: in
      the hypothalamus by measuring immunoreactive (ir) cGnRH-I and cGnRH-II; in the
      anterior pituitary gland by measuring plasma luteinizing hormone (LH); and in the
      gonads by measuring gonadal volume and function. We found that water restriction
      caused a reduction in circulating LH concentrations and that testis volume was
      more likely to decrease in water restricted than in control birds. Subsequent
      short-term return to ad libitum water availability caused LH to return to
      baseline in water restricted birds. These changes occurred without significant
      changes in ir-cGnRH-I, ir-cGnRH-II, or in testis function. These data suggest
      that in these opportunistic breeders, an inhibition of parts of the reproductive
      axis is not necessarily correlated with full inactivation of reproductive
      potential. GnRH-ir cells in the hypothalamus appear to remain active and able to
      respond to subsequent stimulation.

PMID- 16415570
TI  - Distribution of neuropeptide FF-like immunoreactivity in the brain of Dermophis
      mexicanus (Amphibia; Gymnophiona): comparison with FMRFamide immunoreactivity.
AB  - Neuropeptide FF (NPFF) is an FMRFamide-related peptide widely distributed in the
      mammalian brain. NPFF immunohistochemistry labeled cell bodies in a few locations
      and dense fiber networks throughout the brain. Recently, the distribution of NPFF
      immunoreactive (NPFF-ir) cells and fibers in the brain of anuran and urodele
      amphibians was studied and, as in mammals, significant species differences were
      noted. To further assess general and derived features of the NPFF-containing
      neuron system in amphibians, we have investigated the distribution of NPFF-ir
      cell bodies and fibers in the brain of the gymnophionan Dermophis mexicanus by
      means of an antiserum against bovine NPFF. This distribution was compared to that
      of FMRFamide immunoreactivity. Major traits shared with anurans and urodeles were
      the abundant fiber labeling in the ventral telencephalon, hypothalamus, isthmus,
      ventrolateral medulla and dorsal spinal cord. In addition, in the three amphibian
      orders the majority of the NPFF-ir cells were located in the preoptic
      hypothalamic region. However, distinct particular features were present in the
      gymnophionan such as the lack of NPFF-ir cells in the telencephalon, brainstem
      and spinal cord and the absence of NPFF-ir fibers in the hypophysis and the
      olfactory bulbs. This pattern was distinct from that observed for FMRFamide
      distribution. Striking differences were noted in the pallium, caudal hypothalamus
      and midbrain tegmentum where FMRFamide-containing cells were localized. The
      present results in Dermophis support the idea that data from gymnophionans must
      be included when stating the amphibian condition of a given system because
      important variations are obvious when gymnophionans are compared with anurans and
      urodeles.

PMID- 16415569
TI  - Neuroanatomical distribution of cannabinoid receptor gene expression in the brain
      of the rough-skinned newt, Taricha granulosa.
AB  - Type I cannabinoid receptor (CB1) is a G-protein coupled receptor with a
      widespread distribution in the central nervous system in mammals. In a urodele
      amphibian, the rough-skinned newt (Taricha granulosa), recent evidence indicates
      that endogenous cannabinoids (endocannabinoids) mediate behavioral responses to
      acute stress and electrophysiological responses to corticosterone. To identify
      possible sites of action for endocannabinoids, in situ hybridization using a gene
      and species specific cRNA probe was used to label CB1 mRNA in brains of male T.
      granulosa. Labeling of CB1 mRNA in the telencephalon was observed in the
      olfactory bulb and all areas of the pallium, as well as the bed nucleus of the
      stria terminalis and nucleus amygdalae dorsolateralis. The labeling of CB1 mRNA
      was also found in regions of the preoptic area, thalamus, midbrain tegmentum and
      tectum, cerebellum, and the stratum griseum of the hindbrain. A notable
      difference in CB1 labeling between this amphibian and mammals is the abundance of
      labeling in areas associated with olfaction (anterior olfactory nuclei, nucleus
      amygdalae dorsolateralis, and lateral pallium), which hints that endocannabinoids
      might modulate responses to odors as well as pheromones. This widespread
      distribution of CB1 labeling, particularly in sensory and motor control centers,
      fits with prior results showing that endocannabinoids modulate sensorimotor
      processing and behavioral output in this species. The distribution of CB1 in the
      brain of T. granulosa was in many of the same sites previously observed in the
      brain of the anuran amphibian, Xenopus laevis, as well as those of different
      species of mammals, suggesting that endocannabinoid signaling pathways are
      conserved.

PMID- 16415572
TI  - Structural changes of the corpus callosum in mild cognitive impairment and
      Alzheimer's disease.
AB  - BACKGROUND: Although previous studies demonstrate significant atrophy of the
      corpus callosum (CC) in patients with Alzheimer's disease (AD), CC alterations in
      mild cognitive impairment have not been investigated yet. METHODS: 21 subjects
      with mild cognitive impairment, 10 with AD and 21 healthy controls were
      investigated using magnetic resonance imaging. In the mid-sagittal slice the CC
      was traced manually. Additionally, voxel-based morphometry (VBM) was performed.
      RESULTS: The CC was significantly smaller in patients with AD compared to healthy
      controls in both manual tracing and VBM. The atrophy was prominent in rostral
      parts of the CC. In subjects with mild cognitive impairment, the two rostral CC
      segments were smaller compared to controls when manually traced. In contrast, VBM
      revealed no significant difference between subjects with mild cognitive
      impairment and controls. CONCLUSION: Manual tracing was more sensitive in
      detecting discrete structural CC changes than VBM. Alterations of the CC in mild
      cognitive impairment rank in between normal aging and AD, supporting the
      hypothesis that mild cognitive impairment most often represents a preclinical
      stage of AD.

PMID- 16415571
TI  - Behavioral flexibility positively correlated with relative brain volume in
      predatory bats.
AB  - We investigated the potential relationships between foraging strategies and
      relative brain and brain region volumes in predatory (animal-eating) echolocating
      bats. The species we considered represent the ancestral state for the order and
      approximately 70% of living bat species. The two dominant foraging strategies
      used by echolocating predatory bats are substrate-gleaning (taking prey from
      surfaces) and aerial hawking (taking airborne prey). We used species-specific
      behavioral, morphological, and ecological data to classify each of 59 predatory
      species as one of the following: (1) ground gleaning, (2) behaviorally flexible
      (i.e., known to both glean and hawk prey), (3) clutter tolerant aerial hawking,
      or (4) open-space aerial hawking. In analyses using both species level data and
      phylogenetically independent contrasts, relative brain size was larger in
      behaviorally flexible species. Further, relative neocortex volume was
      significantly reduced in bats that aerially hawk prey primarily in open spaces.
      Conversely, our foraging behavior index did not account for variability in
      hippocampus and inferior colliculus volume and we discuss these results in the
      context of past research.

PMID- 16415574
TI  - The concept of cathemerality: history and definition.
AB  - During a field study in 1974 it was noticed, and further fieldwork in 1977 and
      1980 confirmed, that the activity of the Mayotte lemur, Eulemur fulvus fulvus, is
      distributed fairly evenly throughout the daily 24-hour cycle: by a very crude
      approximation the daytime activity:rest ratio averages 0.271, while the night
      time ratio averages 0.283. In 1978 I proposed the new word 'cathemeral',
      compounded from the Greek roots kappaalphataualpha (through) and
      etamuepsilonrhoalpha (the day), to describe this unusual activity pattern, though
      for reasons described in this article the term was not formally published until
      1988. Since then cathemeral activity has been routinely recorded, with some
      variation, in species of the strepsirhine genera Eulemur and Hapalemur; and in
      one form or another it apparently also occurs, at least occasionally, among
      platyrrhines (species of Aotus and Alouatta) as well as among a variety of non
      primate mammals. It may well thus be a more widespread activity pattern than
      earlier appreciated.

PMID- 16415575
TI  - Polyphasic activity patterns in small mammals.
AB  - Cathemeral species are routinely active during the day, the night and at
      twilight. For the majority of species it is advantageous to specialize on the
      environmental conditions of a particular phase of the 24-hour day, so this rather
      uncommon type of activity must be a consequence of specific constraints. Good
      examples are the polyphasic activity patterns found in some small mammals. In
      shrews, with small body size and extremely high metabolic rate, polyphasic
      activity represents a simple short-term hunger cycle. In voles the short-term
      rhythm is triggered by an additional endogenous ultradian clock that interacts
      with the common circadian system, which probably is functionally related to
      endosymbiont digestion of cellulose-rich food. The activity bouts of individuals
      are synchronized on the population level to spread predation risk. As cathemeral
      species, voles are not specifically adapted to particular light conditions, but
      they are also not restricted to a particular activity phase. Therefore, the
      benefits from flexible responses in activity timing to environmental challenges
      may compensate for the disadvantages of not being specialized.

PMID- 16415576
TI  - Eye morphology in cathemeral lemurids and other mammals.
AB  - The visual systems of cathemeral mammals are subject to selection pressures that
      are not encountered by strictly diurnal or nocturnal species. In particular, the
      cathemeral eye and retina must be able to function effectively across a broad
      range of ambient light intensities. This paper provides a review of the current
      state of knowledge regarding the visual anatomy of cathemeral primates, and
      presents an analysis of the influence of cathemerality on eye morphology in the
      genus Eulemur. Due to the mutual antagonism between most adaptations for
      increased visual acuity and sensitivity, cathemeral lemurs are expected to
      resemble other cathemeral mammals in having eye morphologies that are
      intermediate between those of diurnal and nocturnal close relatives. However, if
      lemurs only recently adopted cathemeral activity patterns, then cathemeral
      lemurids would be expected to demonstrate eye morphologies more comparable to
      those of nocturnal strepsirrhines. Both predictions were tested through a
      comparative study of relative cornea size in mammals. Intact eyes were collected
      from 147 specimens of 55 primate species, and relative corneal dimensions were
      compared to measurements taken from a large sample of non-primate mammals. These
      data reveal that the five extant species of the cathemeral genus Eulemur have
      relative cornea sizes intermediate between those of diurnal and nocturnal
      strepsirrhines. Moreover, all Eulemur species have relative cornea sizes that are
      comparable to those of cathemeral non-primate mammals and significantly smaller
      than those of nocturnal mammals. These results suggest that Eulemur species
      resemble other cathemeral mammals in having eyes that are adapted to function
      under variable environmental light levels. These results also suggest that
      cathemerality is a relatively ancient adaptation in Eulemur that was present in
      the last common ancestor of the genus (ca. 8-12 MYA).

PMID- 16415577
TI  - A re-evaluation of the role of vision in the activity and communication of
      nocturnal primates.
AB  - This paper examines the importance of vision in the lives of nocturnal primates
      in comparison to diurnal and cathemeral species. Vision is the major sense in all
      primates and there is evidence that the eyesight of nocturnal species is more
      acute and variable than has previously been recognized. Case studies of the
      behaviour of a galago and a loris in open woodland habitats in relation to
      ambient light show that Galago moholi males are more likely to travel between
      clumps of vegetation along the ground when the moon is up, and during periods of
      twilight, whereas they retreat to more continuous vegetation and travel less when
      the moon sets. This is interpreted as a strategy for avoiding predators that hunt
      on the ground when it is dark. The travel distances of Loris lydekkerianus are
      not affected by moonlight but this species reduces its choice of food items from
      more mobile prey to mainly ants when the moon sets, indicating the importance of
      light when searching for high-energy supplements to its staple diet. Evidence is
      presented for the first time to indicate key aspects of nocturnal vision that
      would benefit from further research. It is suggested that the light and dark
      facial markings of many species convey information about species and individual
      identity when animals approach each other at night. Differences in the colour of
      the reflective eye-shine, and behavioural responses displayed when exposed to
      white torchlight, point to different kinds of nocturnal vision that are suited to
      each niche, including the possibility of some degree of colour discrimination.
      The ability of even specialist nocturnal species to see well in broad daylight
      demonstrates an inherent flexibility that would enable movement into diurnal
      niches. The major differences in the sensitivity and perceptual anatomy of
      diurnal lemurs compared to diurnal anthropoids, and the emergence of
      cathemerality in lemurs, is interpreted as a reflection of evolution from
      different ancestral stocks in very different ecosystems, and not a recent shift
      towards diurnality due to human disturbance.

PMID- 16415579
TI  - Chronobiological background to cathemerality: circadian rhythms in Eulemur fulvus
      albifrons (Prosimii) and Aotus azarai boliviensis (Anthropoidea).
AB  - Cathemeral activity, in which the animals' motor activity is almost evenly
      distributed throughout the dark and the light portion of the day, has been
      described in various lemur genera (Eulemur, Hapalemur) and in the owl monkey
      Aotus azarai of the Argentinean Chaco. Proximate and ultimate factors responsible
      for this behaviour are still being debated. However, the chronobiological
      background of the behaviour has largely been ignored. We studied E. fulvus
      albifrons and A. a. boliviensis under controlled laboratory conditions to assess
      whether their activity rhythm is endogenously regulated by a circadian timing
      system that obeys general rules found in other mammals, or whether there are
      characteristic differences. To this end, we carried out long-term activity
      recordings on individuals of both subspecies kept under constant light and
      various light-dark cycles (LDs) using a PC-controlled electro-acoustic device in
      combination with telemetric body temperature measurements. Both subspecies
      developed free-running circadian activity and body temperature rhythms with
      periods deviating from 24 h in constant light, and LDs turned out to be the most
      efficient Zeitgeber synchronizing this endogenous rhythmicity to the external 24
      hour day. The luminosity prevailing during the dark time of the LD had a decisive
      effect on levels of activity in the lemurs and induced strong masking effects on
      their circadian activity pattern. The results indicate that, from a
      chronobiological viewpoint, both species should be considered as dark active
      primates. Their diel activity rhythm is regulated by a normally responding
      circadian timing system and strong activity inhibiting or enhancing direct
      effects of light intensity. Thus, hypotheses on proximate and/or ultimate factors
      of cathemerality in primates must also consider its circadian background.

PMID- 16415578
TI  - Why be diurnal? Or, why not be cathemeral?
AB  - As a behavioural strategy, cathemerality is thought to confer considerable
      advantages by allowing animals to extend activity flexibly into either the
      diurnal or nocturnal phase in response to the prevailing ecological conditions.
      Factors such as temperature, access to food sources and minimising the risk of
      predation are all thought to be important in promoting cathemerality, although
      previous studies have produced inconsistent results. This paper adopts a
      different approach by first asking whether an obligate diurnal species, the
      chacma baboon (Papio hamadryas ursinus), exhibits seasonal variation in
      behavioural flexibility in response to annual cycles of day length. While short
      day lengths are an important constraint on the activity of the baboons at De Hoop
      Nature Reserve, South Africa, long summer days permit considerable flexibility in
      thermoregulatory response, diet selection and patterns of habitat choice. Given
      that baboons adapt flexibly in response to a relaxation of time constraints, the
      question thus arises as to why diurnal and nocturnal primates do not adopt
      cathemeral activity patterns when time is constrained? For baboons, the costs of
      predation appear to prohibit exploitation of the nocturnal phase and it is likely
      that such constraints are true of most primates. It thus follows that
      Madagascar's predatory environment must in some way permit or select for a
      cathemeral lifestyle. The importance of the predation by fossa (Cryptoprocta
      ferox) on the evolution of cathemerality is discussed.

PMID- 16415580
TI  - Influence of abiotic factors on cathemeral activity: the case of Eulemur fulvus
      collaris in the littoral forest of Madagascar.
AB  - The role environmental factors play in influencing circadian rhythms in natural
      habitats is still poorly described in primates, especially for those taxa with an
      activity cycle extended over the 24-hour cycle. In this paper, we elucidate the
      importance of abiotic factors in entraining the activity of cathemeral primates,
      focussing on results from a long-term study of Eulemur fulvus collaris (collared
      brown lemur) in south-eastern Malagasy littoral forest. Two groups of lemurs were
      followed for 60 whole-day and 59 whole-night observation periods over 14 months.
      Diurnal and nocturnal observations were equally distributed among moon phases and
      seasons. Temperature and humidity were recorded hourly by automatic data loggers.
      The littoral forest has a climatic environment where rainfall and humidity are
      uncorrelated with temperature and photoperiod. Diurnal and nocturnal activity
      varied seasonally, with the former increasing significantly with extended day
      length and the latter increasing significantly with shortened day length. Dusk
      seemed to act as a primary zeitgeber for these lemurs, coordinating the onset of
      evening activity throughout the entire year. Lunar phase and the nocturnal
      luminosity index correlated positively with the duration of nocturnal activity
      and negatively with the length of diurnal activity. Temperature was positively
      associated with diurnal activity but did not seem to influence lemur rhythms at
      night. Finally, lemur nocturnal activity significantly decreased when levels of
      humidity and rainfall were high. Cathemeral biorhythm is triggered by zeitgebers
      and influenced by masking factors. The activity of collared brown lemurs appears
      to be seasonally influenced by photoperiod and directly modulated by nocturnal
      ambient luminosity. These results are discussed by comparing data from other
      cathemeral species living in various climatic situations.

PMID- 16415581
TI  - Cathemerality and lunar periodicity of activity rhythms in owl monkeys of the
      Argentinian Chaco.
AB  - Although most South American owl monkeys are mainly nocturnal, Aotus azarai
      azarai of the Argentinean Chaco regularly shows diurnal activity. In this study
      we examined the strong influence of moonlight on its diurnal and nocturnal
      activity, as well as the interaction of moonlight effects with other exogenous
      factors. We analyzed long-term automated activity recordings obtained with
      accelerometer collars from 7 owl monkeys during 2003 and 2004. Our data show
      marked lunar periodic and seasonal modulations of the owl monkeys' activity
      pattern. On full moon days they were active throughout the whole night and
      displayed reduced activity during the day. With a new moon, activity decreased
      during the dark portion of the night, peaked during dawn and dusk and extended
      over the bright morning hours. Waxing and waning moons induced a significant
      increase in activity during the first and the second half of the night,
      respectively. During the cold winter months the monkeys displayed twice as much
      activity throughout the warmer bright part of the day than during the rest of the
      year. These findings indicate that A. a. azarai is mainly a dark-active species,
      but is still able to shift a considerable portion of activity into the bright
      part of the day if unfavourable lighting and/or temperature conditions prevail
      during the night.

PMID- 16415582
TI  - A note on the activity cycle of captive white-fronted lemurs (Eulemur fulvus
      albifrons).
AB  - We studied the activity cycle of captive-born white-fronted lemurs (Eulemur
      fulvus albifrons) at Zurich Zoo with the aim to discuss current hypotheses on the
      evolution of cathemerality in lemurs. In contrast to their relatives in the wild,
      these lemurs were active exclusively during the day. If cathemerality is a
      strategy to increase food intake or to avoid predators, then nocturnal activity
      is not essential for captive animals and may be suppressed simply due to the
      absence of stimuli. This suggests that cathemerality includes a distinct element
      of flexibility regarding the distribution of diurnal and nocturnal activity, with
      the option to omit nightly activities.

PMID- 16415583
TI  - Predation and cathemerality. Comparing the impact of predators on the activity
      patterns of lemurids and ceboids.
AB  - The removal, or absence, of predatory species could be a contributing proximate
      factor to the rise of primate cathemerality. But predators themselves can also be
      cathemeral, so cathemerality could well be an evolutionary stable strategy. From
      a comparative perspective, it appears that the effect of predatory species cannot
      provide a unitary explanation for cathemerality. Varying distributions and
      population densities of predators, especially raptors, may be key factors in owl
      monkey (Aotus) cathemerality, but temperature and lunar cycle variation have also
      been implicated. In Madagascar, while raptors are potential predators of lemur
      species, the cathemerality of Eulemur species coincides with that of the fossa
      (Cryptoprocta ferox), a major predatory threat to lemurs. Thus, lemurid
      cathemerality may be more parsimoniously explained as an evolutionary stable
      strategy.

PMID- 16415584
TI  - Cathemerality in the Mayotte brown lemur (Eulemur fulvus): seasonality and food
      quality.
AB  - In past decades, cathemerality--as defined by Tattersall [1987]--has been
      documented in two primate families: Cebidae and Lemuridae. In the Lemuridae, in
      particular the genus Eulemur, cathemeral activity seems to be a regular
      behavioural trait. Nevertheless, ultimate and proximate determinants responsible
      for this behaviour remain unclear. In this study, in a dry and deciduous forest
      on Mayotte (Comoro Archipelago), activities of 4 female brown lemurs (Eulemur
      fulvus fulvus) were recorded by focal animal sampling during the daylight period
      and by scan sampling on their respective groups during the night. Horizontal
      distances travelled by females and groups were measured using GPS. During the
      daylight period, food intakes were estimated in grams by extrapolation of
      counting of mouthfuls after weighing a large sample of plant parts eaten. Crude
      protein, crude lipid, soluble sugar and crude fibre were analyzed for each
      seasonal reconstituted diet. Records of temperature and rainfall were supplied by
      a local meteorological station. Observations confirmed cathemerality in the
      Mayotte brown lemur as reported by Tattersall in 1977. During the dry season, the
      animals increased their nocturnal activity--substantially increasing the time
      devoted to feeding and moving overall, but especially at night--and were less
      active during the daylight period. The quality of their diet in the dry season
      was poorer than that in the wet season, with soluble sugar content and protein
      content decreasing and fibre content increasing slightly. As a result, Mayotte
      brown lemurs may need to extend their foraging activity over the 24-hour cycle to
      balance nutritional requirements.

PMID- 16415585
TI  - The evolution of cathemerality in primates and other mammals: a comparative and
      chronoecological approach.
AB  - Non-primate mammalian activity cycles are highly variable across and within
      taxonomic groups. In contrast, the order Primates has historically been
      recognized as displaying a diurnal-nocturnal dichotomy that mapped, for the most
      part, onto the taxonomic division between haplorhines and strepsirhines. However,
      it has become clear over the past two decades that activity cycles in primates
      are not quite so clear cut. Some primate species--like many large herbivorous
      mammals, mustelids, microtine rodents, and shrews--exhibit activity both at night
      and during the day. This activity pattern is often polyphasic or ultradian
      (several short activity bouts per 24-hour period), in contrast to the generally
      monophasic pattern (one long bout of activity per 24-hour period) observed in
      diurnal and nocturnal mammals. Alternatively, it can vary on a seasonal basis,
      with nocturnal activity exhibited during one season, and diurnal activity during
      the other season. The term now generally employed to describe the exploitation of
      both diurnal and nocturnal phases in primates is 'cathemeral'. Cathemerality has
      been documented in one haplorhine, the owl monkey, Aotus azarai, in the
      Paraguayan and Argentinian Chaco and in several Malagasy strepsirhines, including
      Eulemur spp., Hapalemur sp. and Lemur catta. In this paper, we review patterns of
      day-night activity in primates and other mammals and investigate the potential
      ecological and physiological bases underlying such 24-hour activity. Secondly, we
      will consider the role of cathemerality in primate evolution.

PMID- 16415586
TI  - Ser/Thr/Tyr protein phosphorylation in bacteria - for long time neglected, now
      well established.
AB  - The first clearly established example of Ser/Thr/Tyr phosphorylation of a
      bacterial protein was isocitrate dehydrogenase. In 1979, 25 years after the
      discovery of protein phosphorylation in eukaryotes, this enzyme was reported to
      become phosphorylated on a serine residue. In subsequent years, numerous other
      bacterial proteins phosphorylated on Ser, Thr or Tyr were discovered and the
      corresponding protein kinases and P-protein phosphatases were identified. These
      protein modifications regulate all kinds of physiological processes. Ser/Thr/Tyr
      phosphorylation in bacteria therefore seems to play a similar important role as
      in eukaryotes. Surprisingly, many bacterial protein kinases do not exhibit any
      similarity to eukaryotic protein kinases, but rather resemble nucleotide-binding
      proteins or kinases phosphorylating diverse low-molecular-weight substrates.

PMID- 16415587
TI  - Control of isocitrate dehydrogenase catalytic activity by protein phosphorylation
      in Escherichia coli.
AB  - During aerobic growth of Escherichia coli on acetate as sole source of carbon and
      energy, the organism requires the operation of the glyoxylate bypass enzymes,
      namely isocitrate lyase (ICL) and the anaplerotic enzyme malate synthase (MS).
      Under these conditions, the glyoxylate bypass enzyme ICL is in direct competition
      with the Krebs cycle enzyme isocitrate dehydrogenase (ICDH) for their common
      substrate and although ICDH has a much higher affinity for isocitrate, flux of
      carbon through ICL is assured by virtue of high intracellular level of isocitrate
      and the reversible phosphorylation/inactivation of a large fraction of ICDH.
      Reversible inactivation is due to reversible phosphorylation catalysed by ICDH
      kinase/phosphatase, which harbours both catalytic activities on the same
      polypeptide. The catalytic activities of ICDH kinase/phosphatase constitute a
      moiety conserved cycle, require ATP and exhibit 'zero-order ultrasensitivity'.
      The structural gene encoding ICDH kinase/phosphatase (aceK) together with those
      encoding ICL (aceA) and MS (aceB) form an operon (aceBAK; otherwise known as the
      ace operon) the expression of which is intricately regulated at the
      transcriptional level by IclR, FadR, FruR and IHF. Although ICDH, an NADP(+)
      dependent, non-allosteric dimer, can be phosphorylated at multiple sites, it is
      the phosphorylation of the Ser-113 residue that renders the enzyme catalytically
      inactive as it prevents isocitrate from binding to the active site, which is a
      consequence of the negative charge carried on phosphoserine 113 and the
      conformational change associated with it. The ICDH molecule readily undergo
      domain shifts and/or induced-fit conformational changes to accommodate the
      binding of ICDH kinase/phosphatase, the function of which has now been shown to
      be central to successful adaptation and growth of E. coli and related genera on
      acetate and fatty acids.

PMID- 16415588
TI  - Factors that modulate the Pkn4 kinase cascade in Myxococcus xanthus.
AB  - Myxococcus xanthus, a gram-negative developmental bacterium, contains a large
      number of protein Ser/Thr kinases (PSTKs). Among these PSTKs, Pkn4 is shown to be
      6-phosphofructokinase (PFK) kinase. PFK associates with the regulatory domain of
      Pkn4 (Pkn4RD) and is activated 2.7-fold upon phosphorylation at Thr-226 by Pkn4.
      The activation of PFK is required to consume glycogen accumulated during early
      development and is essential for efficient sporulation. Three new factors, MkapA,
      MkapB and MkapC have been identified that associate with Pkn4 by the yeast two
      hybrid screen and each contains well-known protein-protein interaction domains.
      MkapB interacts with Pkn4 in a phosphorylation-dependent manner and remains
      associated with Pkn4 after its phosphorylation. Binding of MkapB to Pkn4 prevents
      the interaction of Pkn4 with PFK and consequently PFK phosphorylation and
      activation. A pfk-pkn4 deletion mutant accumulates glycogen at a rate two folds
      higher than the parent strain, DZF1, at the stationary phase and early
      development stage, it is unable to consume glycogen during development and
      produces only 3.4% of the DZF1 spore yield. In contrast, an mkapB deletion mutant
      exhibits a 24 h delay in fruiting body formation, accumulates less glycogen in
      the stationary phase and gives rise to 6.4% of the DZF1 spore yield. In addition
      to Pkn4, MkapA associates with other membrane-associated PSTKs, Pkn1, Pkn2, Pkn8
      and Pkn9, while MkapB associates with Pkn8 and Pkn9, and MkapC with Pkn8. These
      results indicate that there are complex PSTK networks in M. xanthus sharing
      common modulating factors.

PMID- 16415589
TI  - Protein phosphorylation on Ser, Thr and Tyr residues in cyanobacteria.
AB  - Cyanobacteria belong to an extremely diverse group of gram-negative prokaryotes.
      They are all able to perform oxygen-evolving photosynthesis, but differ in
      morphology, ecological habitats, and physiology. This diversity is also reflected
      in the complexity of regulatory proteins involved in protein phosphorylation on
      Ser, Thr and Tyr residues. For those strains whose genomes are completely
      sequenced, for example, the number of genes identified so far that encode Ser/Thr
      and Tyr kinases range from none to 52. Genetic, molecular as well as functional
      genomic analyses demonstrate that Ser/Thr and Tyr kinases and phosphatases are
      involved in the regulation of a variety of activities according to changes in
      growth conditions or cell metabolism, such as cell motility, carbon and nitrogen
      metabolism, photosynthesis and stress response. The major challenge in the near
      future is to integrate these components into signaling pathways and identify
      their targets. Some of the Ser/Thr and Tyr kinases and phosphatases are expected
      to interact with classical two-component signaling pathways.

PMID- 16415590
TI  - Structure/function studies of Ser/Thr and Tyr protein phosphorylation in
      Mycobacterium tuberculosis.
AB  - Many bacterial species express 'eukaryotic-like' Ser/Thr or Tyr protein kinases
      and phosphatases that are candidate mediators of developmental changes and
      host/pathogen interactions. The biological functions of these systems are largely
      unknown. Recent genetic, biochemical and structural studies have begun to
      establish a framework for understanding the systems for Ser/Thr and Tyr protein
      phosphorylation in Mycobacterium tuberculosis (Mtb). Ser/Thr protein kinases
      (STPKs) appear to regulate diverse processes including cell division and
      molecular transport. Proposed protein substrates of the STPKs include putative
      regulatory proteins, as well as six proteins containing Forkhead-associated
      domains. Structures of domains of receptor STPKs and all three Mtb Ser/Thr or Tyr
      phosphatases afford an initial description of the principal modules that mediate
      bacterial STPK signaling. These studies revealed that universal mechanisms of
      regulation and substrate recognition govern the functions of prokaryotic and
      eukaryotic STPKs. Several structures also support novel mechanisms of regulation,
      including dimerization of STPKs, metal-ion binding to PstP and substrate mimicry
      in PtpB.

PMID- 16415592
TI  - Protein-tyrosine phosphorylation in Bacillus subtilis.
AB  - In recent years bacterial protein-tyrosine kinases have been found to
      phosphorylate a growing number of protein substrates, including RNA polymerase
      sigma factors, UDP-glucose dehydrogenases and single-stranded DNA-binding
      proteins. The activity of these protein substrates was affected by tyrosine
      phosphorylation, indicating that this post-translational modification could
      regulate physiological processes ranging from stress response and
      exopolysaccharide synthesis to DNA metabolism. Some interesting work in this
      field was done in Bacillus subtilis, and we here present the current state of
      knowledge on protein-tyrosine phosphorylation in this gram-positive model
      organism. With its two kinases, two kinase modulators, three phosphatases and at
      least four different tyrosine-phosphorylated substrates, B. subtilis is the
      bacterium with the highest number of presently known participants in the global
      network of protein-tyrosine phosphorylation. We discuss the approaches currently
      used to chart this network: ranging from studies of substrate specificity and the
      physiological role of tyrosine phosphorylation of individual enzymes to the
      global approaches at the level of systems biology.

PMID- 16415591
TI  - A new tyrosine phosphorylation mechanism involved in signal transduction in
      Bacillus subtilis.
AB  - A new kind of prokaryotic protein tyrosine kinase was recently discovered,
      utilizing a guanidino-phosphotransferase domain for its kinase activity.
      Guanidino kinase domains originate from eukaryotic phosphagen kinases, a family
      of phosphoryl transfer enzymes with no homology to the serine/threonine and
      tyrosine kinase superfamily. Nevertheless, this kinase, McsB, exhibits the main
      structural and functional properties of prokaryotic tyrosine kinases. Tyrosine
      phosphorylation in bacteria is predominantly described to be involved in the
      regulation of exopolysaccharide synthesis and is therefore required for biofilm
      formation and virulence. McsB on the other hand modulates together with its
      activator protein, McsA, the activity of the repressor of the class III heat
      shock genes in B. subtilis. The analogy of the kinase mechanism of McsB to
      tyrosine kinases implicates that tyrosine kinases may harbor various and
      independently evolved domains for ATP-binding/hydrolysis and the transfer of the
      gamma-phosphate of ATP onto tyrosine residues.

PMID- 16415593
TI  - Role of protein phosphorylation on serine/threonine and tyrosine in the virulence
      of bacterial pathogens.
AB  - Bacterial pathogens have developed a diversity of strategies to interact with
      host cells, manipulate their behaviors, and thus to survive and propagate. During
      the process of pathogenesis, phosphorylation of proteins on hydroxyl amino acids
      (serine, threonine, tyrosine) occurs at different stages, including cell-cell
      interaction and adherence, translocation of bacterial effectors into host cells,
      and changes in host cellular structure and function induced by infection. The
      phosphorylation reactions are catalyzed in a reversible fashion by specific
      protein kinases and phosphatases that belong to either the invading bacterial
      cells or the infected eukaryotic host cells. Among the various virulence factors
      involved in bacterial pathogenesis, special attention has been paid recently to
      the cell wall components, exopolysaccharides. A major breakthrough has been made
      by showing the existence of a biological link between the activity of certain
      protein-tyrosine kinases/phosphatases and the production and/or transport of
      surface polysaccharides. In addition, genetic studies have revealed a key role
      played by some serine/threonine kinases in pathogenesis. Considering the
      structural organization and membrane topology of these different kinases, it can
      be envisaged that they operate as one-component systems in signal transduction
      pathways, in the form of single proteins containing input and output domains on
      the same polypeptide chain. From a general standpoint, the demonstration of a
      direct relationship between protein phosphorylation on serine/threonine/tyrosine
      and bacterial virulence represents a novel concept of great importance in
      deciphering the molecular and cellular mechanisms that underlie pathogenesis.

PMID- 16415594
TI  - Interaction between the Yersinia tyrosine phosphatase YopH and its macrophage
      substrate, Fyn-binding protein, Fyb.
AB  - Pathogenic Yersinia species can evade phagocytosis by injecting virulence
      effectors that interfere with the phagocytic machinery of host cells. One of
      these virulence effectors is the protein tyrosine phosphatase YopH. Through its
      enzymatic activity, YopH interferes with the initial phagocytic process by
      affecting signalling for cytoskeletal rearrangements. Fyb (Fyn-binding protein),
      which is an immune cell-specific adaptor protein, has been identified as a
      substrate of YopH in macrophages. In this study, the interaction between YopH and
      Fyb is studied. We show that YopH binds to Fyb via different regions in both
      phosphotyrosine-dependent and phosphotyrosine-independent ways. The
      phosphotyrosine substrate binding N-terminal part (1-130) of YopH as well as the
      C-terminal catalytic region binds to Fyb in a phosphotyrosine-dependent manner.
      We also show that a central part of YopH (130-260) interacts with the Fyb C
      terminus (548-783) in a phosphotyrosine-independent manner. Further, we
      demonstrate that the N-terminal binding region of YopH is important for YopH
      mediated functions on macrophages such as dephosphorylation of Fyb, blockage of
      phagocytosis, and cytotoxic effects.

PMID- 16415595
TI  - How seryl-phosphorylated HPr inhibits PrfA, a transcription activator of Listeria
      monocytogenes virulence genes.
AB  - Listeria monocytogenes PrfA, a transcription activator for several virulence
      genes, including the hemolysin-encoding hly, is inhibited by rapidly
      metabolizable carbon sources (glucose, fructose, etc.). This inhibition is not
      mediated via the major carbon catabolite repression mechanism of gram-positive
      bacteria, since inactivation of the catabolite control protein A (CcpA) did not
      prevent the repression of virulence genes by the above sugars. In order to test
      whether the catabolite co-repressor P-Ser-HPr might be involved in PrfA
      regulation, we used a Bacillus subtilis strain (BUG1199) containing L.
      monocytogenes prfA under control of pspac and the lacZ reporter gene fused to the
      PrfA-activated hly promoter. Formation of P-Ser-HPr requires the bifunctional HPr
      kinase/phosphorylase (HprK/P), which, depending on the concentration of certain
      metabolites, either phosphorylates HPr at Ser-46 or dephosphorylates P-Ser-HPr.
      The hprKV267F allele codes for an HprK/P leading to the accumulation of P-Ser
      HPr, since it has normal kinase, but almost no phosphorylase activity.
      Interestingly, introducing hprKV267F into BUG1199 strongly inhibited
      transcription activation by PrfA. Preventing the accumulation of P-Ser-HPr in the
      hprKV267F mutant by replacing Ser-46 in HPr with an alanine restored PrfA
      activity, while ccpA inactivation had no effect. Interestingly, disruption of
      ccpA in the hprK wild-type strain BUG1199 also led to inhibition of PrfA. The
      lowered lacZ expression in the ccpA strain is probably also due to elevated
      amounts of P-Ser-HPr, since it disappeared when Ser-46 in HPr was replaced with
      an alanine. To carry out its catalytic function in sugar transport, HPr of the
      phosphotransferase system (PTS) is also phosphorylated by phosphoenolpyruvate and
      enzyme I at His-15. However, P-Ser-HPr is only very slowly phosphorylated by
      enzyme I, which probably accounts for PrfA inhibition. In agreement with this
      concept, disruption of the enzyme I- or HPr-encoding genes also strongly
      inhibited PrfA activity. PrfA activity therefore seems to depend on a fully
      functional PTS phosphorylation cascade.

PMID- 16415596
TI  - Absence of a difference in the neurosecretory activity of supraoptic nucleus
      vasopressin neurons of neuroleptic-treated schizophrenic patients.
AB  - Dysfunction in water intake and metabolism has frequently been reported in
      schizophrenia. The general population of schizophrenics under neuroleptic
      treatment secretes lower amounts of vasopressin than controls at comparable
      values of plasma osmolality. The purpose of the present study was to investigate
      the synthetic activity of vasopressin neurons of the dorsolateral supraoptic
      nucleus in schizophrenia on postmortem material using a battery of histochemical
      activity markers. Our material consisted of formalin-fixed and paraffin-embedded
      hypothalami from 5 schizophrenic patients under neuroleptic treatment and from 5
      matched controls, obtained from The Netherlands' Brain Bank. DSM-III or DSM-IV
      criteria were used for the clinical diagnosis. The histochemical markers used to
      study the neuronal activity of the magnocellular vasopressin-synthesizing neurons
      were: cell size, size of the Golgi apparatus, and expression of vasopressin and
      tyrosine hydroxylase mRNA by in situ hybridization. Morphometric evaluation and
      statistical analysis (Mann-Whitney U test) were performed. Our results showed no
      statistically significant differences in any of the neuronal activity markers
      between schizophrenic patients and controls. Therefore, the neurosecretory
      activity of vasopressin neurons of the dorsolateral part of the supraoptic
      nucleus does not appear to be changed in schizophrenic patients under medication.
      Since our sample did not include patients with reported polydipsia or
      hyponatremia, prospective investigation is needed to evaluate the above-mentioned
      neuronal activity markers in such a particular subgroup of schizophrenic
      patients.

PMID- 16415597
TI  - Histaminergic neurons are involved in the orexigenic effect of orexin-A.
AB  - Orexin-A is an orexigenic peptide expressed mainly in the hypothalamus. Orexin-A
      increases and anti-orexin-A antibodies decrease food intake. However, the exact
      mechanism by which orexin-A exerts its orexigenic action is not fully elucidated.
      The histaminergic system is known to play a role in feeding behavior and we
      hypothesized that it could be involved in the orexigenic effect of orexin-A. To
      study this, we used histamine knockout animals and pharmacological blockade of
      the histaminergic system and studied the effect of orexin-A on feeding behavior
      and gene expression of neuropeptide Y (NPY). Orexin-A was administered
      intracerebroventricularly and food intake measured in wild-type, histamine H(1)
      receptor knockout or histidine decarboxylase knockout mice. Additionally, we
      administered orexin-A to wild-type mice with pharmacologically blocked H(1)
      receptors or pharmacologically stimulated autoinhibitory H(3)-receptors. By
      quantitative real-time PCR we measured the effect of orexin-A on NPY mRNA
      expression in wild-type and knockout mice. Orexin-A dose-dependently stimulated
      food intake when administered to wild-type mice in doses up to 0.03 microg.
      Orexin-A in a dose of 0.01 microg increased food intake 10-fold in wild-type
      mice, whereas no increase in food intake was seen in either knockout mice or
      pharmacologically manipulated mice. Orexin-A increased NPY mRNA 4-fold in wild
      type mice, whereas no change was observed in knockout mice. We conclude that the
      orexigenic effect of orexin-A is dependent on an intact histaminergic neuronal
      system and seems to involve an H(1)-receptor mechanism.

PMID- 16415598
TI  - Sex differences in methamphetamine-evoked striatal dopamine output are abolished
      following gonadectomy: comparisons with potassium-evoked output and responses in
      prepubertal mice.
AB  - Sex differences are reported for methamphetamine (MA)-induced neurotoxicity of
      the nigrostriatal dopaminergic system. In an attempt to understand some of the
      bases for these differences, we investigated MA-evoked dopamine (DA) responses
      from superfused striatal tissue fragments of intact and male and female CD-1
      mice. These responses were compared with that of gonadectomized mice, potassium
      evoked DA responses in intact mice and responses in prepubertal mice. In
      experiment 1, DA responses were tested using infusion of MA at doses of 1, 10,
      100 and 1,000 microM. In intact mice, mean peak MA-evoked DA responses were
      consistently increased and significantly greater in male vs. female mice at the
      1,000 microM dose. No such significant differences were observed between
      gonadectomized male vs. female mice (experiment 2). In contrast to MA, potassium
      stimulated DA responses were increased in intact female mice, with statistically
      significant differences at doses of 30 and 60 mM (experiment 3). No statistically
      significant differences between intact prepubertal male and female mice were
      obtained in response to a 1,000 microM dose of MA (experiment 4) or to a 60 mM
      dose of potassium (experiment 5). These results indicate that intact male mice
      show greater sensitivity to MA-evoked DA output. This sex difference is abolished
      following gonadectomy, is not observed with potassium, nor is it present in
      prepubertal mice. The increased sensitivity to MA shown by intact males may be
      related to the greater degree of striatal dopaminergic neurotoxicity observed in
      male mice in response to this psychostimulant and appears to be attributable to
      differences in gonadal steroid hormones between male and female mice.

PMID- 16415600
TI  - World No Tobacco Day 2005: the role of health professionals.

PMID- 16415599
TI  - Who needs family medicine? (In the curriculum).

PMID- 16415601
TI  - Can we improve survival of patients with heart failure?

PMID- 16415604
TI  - A comparative study of pre-operative with operative diagnosis in acute abdomen.
AB  - In this observational study (from August 2000 to January 2001) 102 patients of
      all age group with non-traumatic acute abdomen were studied to see the negative
      laparotomy rate and the diagnostic accuracy and predictive values of different
      investigations in acute abdomen. The disease was most common in the age group 20
      29 years with male predominance. More than half of the acute abdomen was due to
      the acute appendicitis. Neutrophil leucocyte count had the highest sensitivity
      (91.5%) while Plain X-ray abdomen showed the highest specificity (88.8%) and
      positive predictive value (88.6%) in diagnosing acute abdomen. Urinalysis showed
      the highest negative predictive value (93.3%). Overall diagnostic accuracy was
      78.4%, which was statistically significant (p<0.05). Diagnostic accuracy was
      highest in bowel obstruction (82.4%) and lowest in peritonitis due to viscus
      perforation (69.0%). Negative laparotomy rate was 17.6% in the study, which was
      statistically significant (p<0.05). It was highest with peritonitis due to viscus
      perforation (20.7%), and lowest in bowel obstruction (11.8%).

PMID- 16415606
TI  - Accidental out-of-hospital deliveries: factors influencing delay in arrival to
      maternity hospital.
AB  - OBJECTIVE: To find out various factors influencing delay in arrival to Shree
      Panch Ratna Rajya Laxmi Maternity Hospital leading to accidental - out - of
      hospital delivery. METHODOLOGY: This was a hospital based cross sectional
      descriptive study conducted at maternity hospital, Kathmandu. Women who delivered
      on the way to the maternity hospital during the time period- 060/9/1 to 060/12/
      31 (4 months) were interviewed using a structured questionnaire. RESULTS: The
      prevalence of such deliveries was 45 out of 5703 deliveries i.e. 0.78%. Majority
      of women (n= 37) who had accidental - out - of hospital delivery were of parity 1
      2 group (82.22%), whereas 2 of them were primigravida (4.44%) and 6 of them were
      of group parity 3-4 (13.33%). Economic factor was not responsible for delay for
      majority of women as they could arrange money immediately in emergency situation
      (88.88%) and majority of women had personal money saved for use in emergency
      (71.11%). Accessibility to the hospital was difficult for few women (21.00%) only
      as many women lived within the ring road of Kathmandu valley (48.88%) or outside
      the ring road but within municipality area of Kathmandu valley (31.11%). Only 60%
      of women could get transport easily during daytime only. Eight of them were late
      due to delay in getting transport (17.77%), whereas five patients were late due
      to disturbed / diverted traffic (11.11%). In three cases, transport was not
      available due to Nepal Bundh and delay was due to time taken to arrange ambulance
      (6.66%). Majority of women came for antenatal visits (84.44%) and most of them
      came to maternity hospital for antenatal visits (73.33%). Lack of birth
      preparedness and inadequate counselling during antenatal visits probably
      contributed towards many A-O-H (65.78%). More than half of patients were not
      satisfied with health staff during ANC (63.15%). Many women did not have any
      discussion about place of birth during ANC (73.68%) and many of them had no
      discussion even in the family (36.84%). Seven patients had probably precipitate
      labour (15.55%). 4 patients were returned back home with diagnosis of false
      labour pain (8.88%) and later on they delivered on the way to the hospital.
      SUMMARY AND CONCLUSION: Lack of birth preparedness that involves adequate
      counselling during ANC about symptoms and signs of onset of labour pain and prior
      decision about place of birth together with delay in getting transport or delay
      due to diverted traffic were important factors leading to A-O-H. In addition,
      unusually short duration of labour or dismissing the diagnosis of true onset of
      labour may have accounted for few cases of A-O-H.

PMID- 16415603
TI  - Propranolol is effective in decreasing stress response due to airway manipulation
      and CO2 pneumoperitoneum in patients undergoing laparoscopic cholecystectomy.
AB  - PURPOSE: to study the effect of Propranolol on hemodynamic response due to airway
      manipulation and carbon dioxide pneumoperitoneum on laparoscopic cholecystectomy
      cases. METHODS: 63 patients undergoing laparoscopic cholecystectomy under general
      anaesthesia were randomly divided into 3 groups; group 1 received 1.0 mg of
      Propranolol, group 2 received 0.5 mg of Propranolol and group 3 received 1 ml
      saline 5 minutes before induction of anaesthesia. Haemodynamic parameters were
      recorded for every 5 minutes from basal to 5 minutes after extubation and
      analyzed. RESULTS: Balanced anaesthesia used in our set up is effective in
      decreasing stress response due to airway manipulation (laryngoscopy and
      endotracheal intubation) but not effective in that due to CO2 pneumoperitoneum.
      Propranolol 1 mg 5 minutes before anaesthesia is effective in decreasing stress
      response due to airway manipulation and CO2 pneumoperitoneum in these groups of
      patients. CONCLUSION: Propranolol effectively blunts the stress response due to
      CO2 pneumoperitoneum during laparoscopic cholecystectomy.

PMID- 16415605
TI  - Upper GI endoscopy in children- in an adult suite.
AB  - Although Upper GI endoscopy is commonly performed in adults, paediatric endoscopy
      is not available in many of our referral centres. The efficacy and safety of
      upper GI endoscopy in paediatric age group performed in adult suite of Kathmandu
      Medical College is reviewed. PATIENTS AND METHOD: A retrospective study of
      endoscopies performed on children aged up to 15 years in an adult endoscopy suite
      of Kathmandu medical college over last one year is presented. All cases were the
      referred cases from paediatric unit for various problems. RESULTS: Endoscopy in
      paediatric group comprises only 6% of total upper GI endoscopies performed during
      the same year. Sex ratio was almost equal. Most cases (87%) were performed under
      local anaesthetic and well tolerated by the patients. Recurrent abdominal pain
      (RAP) was the commonest indication and among them one third of cases had
      significant positive finding. CONCLUSION: Upper GI endoscopy is a useful
      diagnostic tool in children. Where specialized paediatric endoscopy units are not
      feasible i.e. developing countries, endoscopic services to children can be safely
      provided in adult endoscopy suite with or without sedation. Upper GI endoscopy is
      well tolerated by children even without sedation.

PMID- 16415607
TI  - A study of sensitivity and resistance of pathogenic micro organisms causing UTI
      in Kathmandu valley.
AB  - A retrospective study was conducted in five hospitals to observe the prevalence
      of organisms causing UTI and their sensitivity to antibiotics. METHODOLOGY:
      Altogether, data from five hundred samples of urine from five hospitals in
      Kathmandu was collected for this study from January 2005 to April 2005. RESULT: A
      total of 244 samples were found to be positive. Altogether six types of organisms
      were isolated as the causative factors. E. coli (49%), S. aureus, (coagulase
      positive) (23%), Proteus species (3.6%), Klebsiella (9.71%), Pseudomonas (0.8%)
      and Citrobacter (2.8%). Analysis of the samples showed that UTI was more common
      in females of younger age group as compared to males. The common age group for
      females was 21-30 years, whereas that for males was 31-40 years in all the
      hospitals except in hospital A, where the maximum number of females was from 31
      40 years and males were between 71-80 years. The most common organism to cause
      UTI was found to be E. coli (49%), followed by S. aureus (23%) and Klebsiella
      (9.71%). All the organisms causing UTI were sensitive to nitrofurantoin and
      amoxycillin and ciprofloxacin was found to be least effective. Similarly, in
      three hospitals, B (88.2%), D (64.7%) and E (65.3%), amoxycillin was found to be
      most effective, amikacin and gentamycin (92.5%) was most effective in hospital C,
      and nitrofurantoin in hospital A (78%). The second commonest organism, i.e., S.
      aureus (23%) was most sensitive to cephalosporin (88.8%) of second generation,
      followed by nitrofurantoin (77.7%), amikacin (80.6%) and norfloxacin (65.5%). The
      third common organism, Klebsiella (9.71%) was most sensitive to norfloxacin (75%)
      and nitrofurantoin (75%). Lastly, Pseudomonas was resistant to all the
      antibiotics in hospital A, D and E, nil in hospital B and sensitive to amikacin
      (100%) in hospital C.

PMID- 16415608
TI  - Intensive care unit drug utilization in a teaching hospital in Nepal.
AB  - OBJECTIVES: The intensive care unit (ICU) is a setting where a large number of
      drugs are administered to patients and the costs of hospitalization and drug
      treatment are high. Information on drug utilization in intensive care units
      (ICUs) are lacking in western Nepal. The present study was carried out to obtain
      information on the basic demographic pattern of the respondents, drug utilization
      during the study period, the antibiotic sensitivity patterns of isolated
      microorganisms and measure drug consumption in defined daily dose (DDD)/ 100 bed
      days. METHODS: A retrospective analysis of patients admitted to the ICU of the
      Manipal Teaching hospital, Pokhara, Nepal during the time period from 01/02/2002
      to 31/05/2002 was carried out. The ICU mortality rate, length of stay greater
      than 7 days and median length of stay were calculated. RESULTS: A total of 259
      individuals were admitted. The ICU mortality rate was 15.4%; median length of
      stay was 4 days. E.coli, H.influenzae, K.pneumoniae, S.aureus and P.aeruginosa
      were the common organisms isolated and were found to be resistant to some of the
      commonly used antibiotics. Mean +/- SD number of drugs and cost of drugs were 5.1
      +/- 2.7 and 1958.5 +/- 1267.8 Nepalese rupees (25.1 +/- 16.2 US dollars). Total
      drug consumption was 356.4 DDD/100 bed-days. Consumption of intravenous fluids
      was 25.8 litres/100 bed-days. CONCLUSIONS: An antibiotic use policy should be
      framed. Formation of a multidisciplinary team to oversee drug use and
      periodically review microbial sensitivity patterns will be helpful. Longitudinal
      surveillance of ICU drug use should be carried out.

PMID- 16415609
TI  - An outbreak of El Tor cholera in Kavre district, Nepal.
AB  - Outbreak of cholera still remains major public health problem in most of the
      developing countries including Nepal. A prospective study was carried out at
      Dhulikhel Hospital, Kathmandu University Teaching Hospital, Kavrepalanchok during
      1st May 2004 to 31st October 2004. A total of 148 stool samples from patients
      with acute diarrhea were collected and further investigated for cholera. The
      study was conducted to establish the causes of the outbreak of acute diarrheal
      disease, antimicrobial profiles of the stool isolates and parasitic co-infection
      in cholera cases. The samples were subjected to standard recommended microbial
      procedures and confirmation of the isolates was done by seroagglutination using
      V.cholerae polyvalent O1 and 0139 antisera and monovalent Ogawa and Inaba
      antisera. Out of the 148 stool samples, 46 cases (31%) were found to be positive
      for V.cholerae serogroup O1, biotype ElTor, serotype Ogawa. Both sexes were
      equally affected. Young age group of less than 30 years were mostly affected.
      Brahmin was the most affected ethnic group. The isolates were sensitive to all
      the antibiotics tested except co-trimoxazole. Among the laboratory confirmed
      cholera cases 30% exhibited co-infection with other parasites among which Giardia
      lamblia and Ascaris lumbricoides were the most common.

PMID- 16415610
TI  - Emotional impact of cadaver dissection: a survey in a medical college in western
      Nepal.
AB  - OBJECTIVES: Adverse physical and psychological effects to human dissection have
      been reported in many studies. In Nepal, the basic science subjects are taught in
      an integrated manner in the first four semesters of the MBBS course. Studies on
      the attitudes of medical students towards anatomy dissection are lacking in
      Nepal. The present study was carried out to obtain information on the present and
      initial perception of medical students on exposure to anatomy dissection and the
      association, if any, of the perception with demographic factors. METHODS: The
      study was carried out among the first, second and third semester students at the
      Manipal College of Medical Sciences, Pokhara using the appraisal of life events
      (ALE) scale in February 2005. Sixty-three first semester, 57 second and 65 third
      semester students successfully completed the questionnaire and their responses
      were taken up for analysis. Information on sex, age, nationality, religion, food
      habits, occupation of parents and selection procedures of respondents was
      collected. The parameters loss, challenge and threat were measured on first
      exposure to dissection and at the time of the study. The scores were compared
      among different categories of students (p< 0.05). RESULTS: 185 of the 225
      students (82.2%) successfully completed the questionnaire. The median initial
      loss, challenge and threat scores were 2, 19 and 4 respectively. The median
      present loss, challenge and threat scores were 1, 20 and 0 respectively. The
      present threat score was higher among second semester students. The initial loss
      was higher among Indians and the present challenge score was higher among
      vegetarians. CONCLUSIONS: The loss and threat score were low compared to that
      reported in a previous study. The challenge scores were higher than those
      reported previously. Majority of students considered anatomy dissection as a
      significant life experience and one which was largely positive. Further studies
      with a larger student population and in other medical colleges are required.

PMID- 16415611
TI  - Trends of acute poisoning in south Karnataka.
AB  - BACKGROUND: In recent times poisoning with agricultural chemicals either
      accidental or suicidal has become common due to easy availability and low cost.
      So it has become essential to find out the burden of poisoning to the victims,
      family and to hospital and morbidity and mortality among the victims. AIMS: To
      determine the trends of poisoning along with various parameters such as mode of
      poisoning, type of poison used, outcome of the poisoning, the most vulnerable age
      group, occupation of the victim, and the marital status. METHOD: A 5 year
      retrospective study in which all the patients of acute poisoning admitted to
      Govt. Wenlock Hospital, Mangalore during the period from 1st Jan 1999 to 31st
      December 2003 were included. A total of 546 cases were admitted due to acute
      poisoning during the study period. RESULTS: Three hundred and eighty (69.6%)
      males and one hundred and sixty six (30.4%) females were admitted to the hospital
      due to poisoning. Organophosphates were the most commonly used suicidal poison
      irrespective of age, sex and occupation of the victim. There were two hundred and
      thirty five cases of male suicidal poisoning and one hundred and twenty six
      female cases of suicidal poisoning. Majority of poisoning cases were seen in
      manual labourers. The increasing trend of poisoning was observed for the period
      of 1999 to 2003 except for the year of 2003. CONCLUSION: The study highlights
      about the problem of poisoning in the region. Since the majority of the victims
      of the poisoning are from low socio economic status. There is economic burden on
      the family members of the victim of poisoning as the earning member of the family
      becomes ill (for treatment), dies (loss of earning member) and also emotional
      setback and disturbance.

PMID- 16415613
TI  - Medical education - changing perspectives.
AB  - Various aspects of medical education have been reviewed with special reference to
      medical institutions in Nepal. The newer trends in teaching methodology like
      audiovisual and computer aided methods are being followed in most of the
      institutions of Nepal. Similarly, attempts are being made to implement integrated
      teaching which, though not perfect, differs from institution to institution. The
      attempts seem to be more or less satisfactory with awareness amongst most of the
      teachers and planners. However, the methods of assessment of the students at
      every level, call for changes and improvement, in the light of modern trends.
      Similarly, the process of selection in medical colleges needs change. The replies
      to the questionnaire given to the students of two batches were very interesting
      and it is worthwhile to undertake such studies in other institutions as well.
      Valid suggestions opined by them should be implemented.

PMID- 16415612
TI  - Anatomic characteristics of foramen vesalius.
AB  - OBJECTIVES: Foramen Vesalius is an inconstant foramen that gives passage to an
      emissary vein that connects pterygoid venous plexus with cavernous sinus, the
      importance of which lies in the fact that an infected thrombus from an
      extracranial source may reach cavernous sinus. This study presents some data on
      characteristics of foramen vesalius. METHODS: We studied 70 sides of 35 dried
      adult human skulls available in the Department of Anatomy, Manipal College of
      Medical Sciences, Pokhara, Nepal. Variation in number and incidence of foramen
      Vesalius were noted. Differences between the right and the left side and between
      the male and the female sex are discussed. MAIN FINDINGS: Foramen Vesalius was
      present in 23 sides (14 right, 9 left) out of the 70 sides observed, the
      incidence being 32.85% (20.0% right side, 12.85% left side) of all the sides
      observed. Incidence of bilateral and unilateral foramen vesalius was 22.85% (8
      out of 35 skulls) and 20% (7 out of 35 skulls) respectively. Foramen vesalius was
      found in 10 sides in males and in 13 sides in females. No remarkable differences
      were observed in the incidence of foramen vesalius between the sides within same
      sex but the incidence was more in females compared to male skulls. SIGNIFICANCE
      OF FINDINGS: Anatomic variations of the foramen vesalius could be explained by
      developmental reasons. Knowledge about characteristics of foramen vesalius and
      its incidence is not only important for anatomists but equally essential for an
      operating surgeon.

PMID- 16415614
TI  - Nepalese medical websites: online Nepalese medical libraries.

PMID- 16415615
TI  - Omental torsion: a case report.
AB  - Omental torsion is a rare cause of acute abdomen. Most often it presents with
      sign and symptoms of acute appendicitis. It is seldom considered in the
      differential diagnosis preoperatively based on clinical findings and the
      diagnosis is only established during surgery. We present a case of omental
      torsion in a middle aged male patient who presented with findings suggestive of
      appendicular perforation and underwent emergency laparotomy.

PMID- 16415617
TI  - Delayed presentation of Sheehan's syndrome: a case report.
AB  - Sheehan's syndrome, though rare, is still one of the commonest causes of
      hypopituitarism in developing countries like ours. The clinical presentation is
      variable with abrupt or insidiously developing pituitary insufficiency after a
      heavy intrapartum or postpartum haemorrhage. We present an elderly lady with this
      syndrome who had slowly progressive panhypopituitarism 24 years after a severe
      haemorrhage associated with the delivery of triplets.

PMID- 16415616
TI  - An unusual presentation of huge cervical fibroid.

PMID- 16415618
TI  - Liver diseases in Nepal.

PMID- 16415619
TI  - A role for trichloroethylene in developing nation anaesthesia.

PMID- 16415620
TI  - Need for renal transplantation programme in Bir Hospital.

PMID- 16415621
TI  - General practice (family medicine): meeting the health care needs of Nepal and
      enriching the medical education of undergraduates.

PMID- 16415622
TI  - Somewhere in the vicinity of Nepal's capital.

PMID- 16415623
TI  - AIDS at altitude.

PMID- 16415624
TI  - Predictors of suicidal ideation for adolescents by gender.
AB  - PURPOSE: The purposes of this study were 1) to examine the differences in
      suicidal ideation and psychological variables by gender, 2) compare the
      contribution of demographic-behavioral variables and psychosocial variables in
      explaining the variance in suicidal ideation, and 3) identify the most important
      predictors of suicidal ideation for male adolescents and female adolescents.
      METHODS: The subjects consisted of 271 male adolescents and 230 female
      adolescents. Data were collected through self-report questionnaires, which were
      constructed to include SSI-C, DEP subscale of the SCL-90-R, PACI, and SWLS. The
      data were analyzed by the SPSS/WIN program. RESULTS: Suicidal ideation differed
      by gender. Depression and family communication differed by gender. The unique
      contribution of demographic-behavioral variables and psychosocial variables in
      explaining the variance in suicidal ideation differed between male adolescents
      and female adolescents. The significant predictors of suicidal ideation for male
      adolescents were life satisfaction, depression, and family communication,
      explaining 28% of the variance in suicidal ideation. The significant predictors
      of suicidal ideation for female adolescents were depression, smoking, and life
      satisfaction, explaining 38% of the variance in suicidal ideation. CONCLUSION:
      The findings of this study suggest that the approach to effective suicide
      prevention program for adolescents should consider gender differences.

PMID- 16415626
TI  - The effect of infant massage on weight gain, physiological and behavioral
      responses in premature infants.
AB  - PURPOSE: The purpose of this study was to evaluate the premature infants'
      responses to infant massage (tactile and kinesthetic stimulation). These
      responses measured by weight, physiological (vagal tone, heart rate, oxygen
      saturation) and behavioral responses (behavioral states, motor activities, and
      behavioral distress). METHODS: This study was conducted using an equivalent
      control pretest-posttest design. The sample was divided into two groups of 13
      infants with gestational age less than 36 weeks at birth, birth weight less than
      2000 g, and no congenital anomalies. The experimental group received the massage
      intervention twice daily for 10 days. The data were collected for 10 minutes
      prior to and 10 minutes after the massage. RESULTS: The vagal tone was
      significantly higher after massage than before massage in the experimental group,
      while no change in the control group. The experimental group had significantly
      higher scores for awake state and motor activity than the control group.
      Significantly greater awake state, more fidgeting or crying, and increased motor
      activity were reported after massage than before massage. CONCLUSIONS: The
      results of this study showed that massage therapy might enhance optimal
      physiological responses and behavioral organization of premature infants. Nursing
      staff in the NICU can use massage to promote the infant's capability to respond
      positively to his environment and to provide developmental support for healthy
      premature infants.

PMID- 16415625
TI  - Predictors of mammography participation among rural Korean women age 40 and over.
AB  - PURPOSE: The study was conducted to identify predictors of mammography screening
      for rural Korean women according to 'Stage of Change' from the Transtheoretical
      Model which, along with the Health Belief Model, formed the theoretical basis for
      this study. METHODS: A cross-sectional descriptive design was utilized. Through
      convenience sampling 432 women were selected from 2 rural areas. Data were
      collected by survey. Health beliefs constructs were measured with Champion's HBM
      Scale-Korea version. Mammography participation was measured using the Stage of
      Mammography Adoption Scale developed by Rakowski, et al. (1992). RESULTS: The
      most frequent stage of mammography adoption was 'contemplation' (40.5%).
      Predictors of stage of mammography adoption included 'mammogram recommended by
      health professional' (beta=0.59, t=16.12, p=.000), 'perceived benefits'
      (beta=0.09, t=2.21, p=.050), 'perceived susceptibility' (beta=0.09, t=1.98,
      p=.050), and 'perceived barriers' (beta= 0.07, t= -2.05, p=.041). 'Mammogram
      recommended by health professional' demonstrated the greatest association with
      having a mammogram. CONCLUSION: Health professionals play key roles in improving
      mammography participation and should recognize the importance of their role in
      cancer prevention and be more actively involved in education and counseling on
      prevention of breast cancer.

PMID- 16415627
TI  - The experiences of family caregiving in a chronic care unit.
AB  - PURPOSE: The main purpose of this critical ethnography was to examines the
      process and discourses through which family caregivers experience while caring
      for their sick family member in a hospital. METHODS: This was achieved by
      conducting in-depth interviews with 12 family caregivers, and by observing their
      caring activities and daily lives in natural settings. The study field was a unit
      for neurologic patients. Data was analyzed using taxonomy, discourse analysis,
      and proxemics. All research work was iteratively processed from March 2003 to
      December 2004. RESULTS: Constant comparative analysis of the data yielded the
      process of becoming a successful family caregiver: encountering the differences
      and chaos as novice; constructing their world of skilled caregivers; and becoming
      a hospital family as experienced caregivers. During the process of becoming an
      experienced hospital family, the discourse of family centered idea guided their
      caring behaviors and daily lives. CONCLUSION: The paternalistic family caregivers
      struggled, cooperated, and harmonized with the patriarchal world of professional
      health care system. During this process of becoming hospital family, professional
      nurses must act as cultural brokers between the lay family caring system and the
      professional caring system.

PMID- 16415628
TI  - Effectiveness of a behavioral intervention program for urinary incontinence in a
      community setting.
AB  - PURPOSE: The purposes of this study were to examine the effectiveness of a
      behavioral intervention program combining pelvic floor muscle exercise with
      bladder training for urinary incontinence and also to conduct follow-up
      assessment after self-training. METHODS: This study was conducted using a non
      equivalent control group, pretest-posttest design. The subjects were 60 middle
      aged women (control group, n=30; intervention group, n=30) who experienced an
      episode of urinary incontinence at least once a week. The program was run over a
      4 week period (once a week) and composed of urinary incontinence education,
      pelvic floor muscle exercise, and bladder training. RESULTS: Overall, there was a
      significant difference in urinary incontinence symptoms and psycho-social
      wellbeing related to urinary incontinence between the treatment and control
      group. Of the variables, weekly leakage frequencies, leakage amounts on each
      occasion, leakage index, frequencies of nocturia, and quality of life were
      significantly different between the groups. Follow-up assessment (9th week)
      indicated that overall incontinence symptoms and psycho-social well-being were
      significantly different between the posttest and follow-up assessments. Most
      variables of incontinence symptoms and psycho-social well-being were
      significantly improved at follow-up assessment versus posttest. CONCLUSIONS: The
      program was overall effective in terms of relieving symptoms and improving psycho
      social well-being related to urinary incontinence, and this effect continued
      after a 4-weeks self-training period. In the respect that this is a community
      based application study, the results can be meaningful and applicable.

PMID- 16415629
TI  - Effectiveness of reality therapy program for schizophrenic patients.
AB  - PURPOSE: The present study aims to verify the effectiveness of the reality
      therapy for patients with schizophrenia. METHODS: It is designed as a quasi
      experimental study by which a nonequivalent control group pretest-posttest is
      conducted. The test was conducted with 30 patients with schizophrenia who were
      hospitalized at a mental hospital in South Korea. Fifteen of the patients
      participated in the reality therapy program while another 15 in the control
      group. The effects are measured by marking scores in the areas of the locus of
      control, self-esteem, and problem-focused stress coping of each participant.
      RESULTS: The general characteristics and dependent variables related to outcome
      variables were controlled to be equal between the two groups. It turns out that
      the internal locus of control, self-esteem, and problem-focused stress coping are
      statistically significant. CONCLUSION: Findings show that the reality therapy
      caused positive changes in terms of the internal locus of control, self-esteem,
      and problem-focused stress coping of the observed schizophrenic patients.

PMID- 16415631
TI  - Comparison of cardiovascular risk profile clusters among industrial workers.
AB  - PURPOSE: The purpose of this study was to identify subgroups of the physical and
      behavioral risk profiles for cardiovascular disease among industrial workers, and
      to examine predicting factors for the subgroups. SAMPLE AND METHOD: Health
      records of 2,616 male and female workers aged 19-56 years who were employed in an
      airplane manufacturing industry were analyzed. Data were analyzed using the
      Latent class cluster analysis. RESULTS: Four different clusters (two high-risk
      groups, one low-risk group, and one normal group) were found and these clusters
      were significantly different by age, gender, and work type (p<.05). The two high
      risk groups had higher chances of drinking alcohol, elevated BMI, FBS, total
      cholesterol, having hypertension, and were significantly older, and had
      relatively high chances of being day workers rather than other groups. The low
      risk group had higher chances of drinking alcohol, higher BMI and total
      cholesterols compared to normal group, and highest portions of current smokers
      and shift workers in the four clusters and their mean BP was within
      prehypertension criteria. CONCLUSION: Industrial nurses should guide the
      lifestyle behaviors and risk factors of the high risk groups for CVD and need to
      intervene early for behavioral change for the low-risk group who are young and
      shift workers. Age, and work environment should be considered in planning for
      targeted preventive interventions for industrial workers.

PMID- 16415630
TI  - Factors related to nurse staffing levels in tertiary and general hospitals.
AB  - BACKGROUND: Adequate staffing is necessary to meet patient care needs and provide
      safe, quality nursing care. In November 1999, the Korean government implemented a
      new staffing policy that differentiates nursing fees for inpatients based on
      nurse-to-bed ratios. The purpose was to prevent hospitals from delegating nursing
      care to family members of patients or paid caregivers, and ultimately
      deteriorating the quality of nursing care services. PURPOSE: To examine nurse
      staffing levels and related factors including hospital, nursing and medical
      staff, and financial characteristics. METHODS: A cross-sectional design was
      employed using two administrative databases, Medical Care Institution Database
      and Medical Claims Data for May 1-31, 2002. Nurse staffing was graded from 1 to
      6, based on grading criteria of nurse-to-bed ratios provided by the policy. The
      study sample consisted of 42 tertiary and 186 general acute care hospitals.
      RESULTS: None of tertiary or general hospitals gained the highest nurse staffing
      of Grade 1 (i.e., less than 2 beds per nurse in tertiary hospitals; less than 2.5
      beds per nurse in general hospitals). Two thirds of the general hospitals had the
      lowest staffing of Grade 6 (i.e., 4 or more beds per nurse in tertiary hospitals;
      4.5 or more beds per nurse in general hospitals). Tertiary hospitals were better
      staffed than general hospitals, and private hospitals had higher staffing levels
      compared to public hospitals. Large-sized general hospitals located in
      metropolitan areas had higher staffing than other general hospitals. Occupancy
      rate was positively related to nurse staffing. A negative relationship between
      nursing assistant and nurse staffing was found in general hospitals. A greater
      number of physician specialists were associated with better nurse staffing.
      CONCLUSIONS: The staffing policy needs to be evaluated and modified to make it
      more effective in leading hospitals to increase nurse staffing.

PMID- 16415634
TI  - Applying the strategy of combination antihypertensive therapy to special
      populations.

PMID- 16415632
TI  - Benign prostatic hyperplasia in community-dwelling elderly in Korea.
AB  - BACKGROUND: This study was done to identify the prevalence of benign prostatic
      hyperplasia (BPH) and BPH-related symptoms among community-dwelling elderly men
      in Korea. In addition, quality of life and health care-seeking behavior were
      explored. METHODS: A total of 417 elderly men were surveyed using the IPSS
      (International Prostatic Symptom Score) and a structured questionnaire on health
      care-seeking behaviors. RESULTS: The prevalence of BPH was 19.7%. Of those with
      BPH, 80.3% reported mild symptoms, 13.2% moderate symptoms, and 6.5% severe
      symptoms. The severity of BPH-related symptoms was significantly correlated with
      quality of life. Among those with BPH, 42.7% had never consulted with anyone
      about their symptoms. CONCLUSIONS: BPH has emerged as a serious public health
      problem in elderly men. Elderly people who experience worse symptoms of BPH have
      a lower quality of life. Many elderly with BPH do not seek health care, mainly
      due to misconceptions about BPH. The provision of educational programs for BPH
      may significantly improve the quality of life of elderly men.

PMID- 16415633
TI  - Nurses' perception of performance and responsibility of patient education.
AB  - PURPOSE: This paper is derived from a larger study of nurses perceptions of their
      role as patient educators. The focus is to examine nurses performance in patient
      education in relation to issues of their perceived responsibility and their
      ability to prioritize patient education. METHOD: A multiple-method survey design,
      using a questionnaire and in-depth interviews, is used to produce a comprehensive
      picture of the research problem examined. RESULT: The findings suggest that
      although nurses consider patient education as an integral part of their care,
      they fail to deliver as much as they desire in the face of work constraints.
      Nurses patient education activities are mainly informal and reactional, in which
      case they can be easily regarded as a low priority when faced with time
      constraints. CONCLUSION: The findings suggest that there is a need for systematic
      approaches that enable the inculcation of patient education into routine daily
      care.

PMID- 16415635
TI  - Dispelling the myth of "aggressive" antihypertensive therapy.
AB  - Data from well designed randomized trials have proven the effectiveness of an
      intensive approach to hypertension management in reducing morbidity and
      mortality. Based on these data, guidelines recommend a blood pressure goal of
      <140/90 mm Hg in the general population, with lower goals for high-risk patients.
      Clinical trials also show that most patients will require at least two
      antihypertensive agents to reach goal. Despite this evidence base, only about one
      third of individuals with hypertension receive sufficient therapy to attain a
      blood pressure of <140/90 mm Hg. Physicians may be reluctant to use multiple
      antihypertensive agents to achieve this goal because they may consider it to be
      "aggressive" and not always in the best interests of the patient, especially in
      those deemed at low risk. Such perceptions may be founded on several myths: 1)
      the approach demands a complex, time-consuming titration-to-response strategy,
      during which the patient may be lost to follow-up; 2) it increases the pill
      burden, which will decrease patient compliance; 3) it increases treatment-related
      side effects; and 4) it is not cost-effective. The availability of fixed-dose
      combinations containing two antihypertensive agents should help to dispel these
      myths. Careful selection of efficacious, well tolerated, once-daily, fixed-dose
      combinations allows goal blood pressure to be achieved quickly in a broad range
      of patients and encourages patient concordance with therapy. Such formulations
      are also cost-effective. Thus, reducing blood pressure using multiple drugs as
      fixed-dose combinations is a strategy that recognizes the multiple
      pathophysiologic changes that lead to hypertension.

PMID- 16415636
TI  - Hypertension--a treatable component of the cardiometabolic syndrome: challenges
      for the primary care physician.
AB  - Patients with the cardiometabolic syndrome (CMS) have an adverse cardiovascular
      risk factor profile, placing them at increased risk of stroke, coronary artery
      disease, chronic kidney disease, and type 2 diabetes mellitus. Although no
      specific treatments for CMS are available per se, prompt recognition and
      treatment of the individual components of the condition can prevent or delay the
      development of comorbidities. Primary care physicians are ideally positioned to
      identify patients with CMS and implement early intervention strategies.
      Hypertension contributes to many complications of CMS, and rigorous blood
      pressure control will help to delay or prevent end-organ vascular damage.
      Achieving blood pressure control to current guideline standards should be eagerly
      sought in the majority of patients through a combination of lifestyle
      modifications and appropriate pharmacologic therapy. Antihypertensive drug choice
      should be personalized, taking into account the CMS determinants present and any
      compelling indications for specific agents. As an initial approach, a thiazide
      diuretic is suitable for most cases of uncomplicated hypertension, although many
      patients will require additional antihypertensives from other classes to achieve
      their blood pressure goal. It is predicted that, due to the increase in unhealthy
      lifestyles, the prevalence of CMS will rise in the coming years. Therefore, by
      meeting the challenge of attaining and maintaining blood pressure control in
      patients with CMS, primary care physicians have the unique opportunity to
      markedly improve the health of the nation.

PMID- 16415637
TI  - Hypertension-related morbidity and mortality in African Americans--why we need to
      do better.
AB  - Almost one third of adults in the United States have hypertension. Prevalence
      data among different racial or ethnic groups indicate that a disproportionate
      number of African Americans have hypertension compared with non-Hispanic whites
      and Mexican Americans. Earlier onset of high blood pressure and greater severity
      of hypertension contribute to a greater burden of hypertensive target organ
      damage in African Americans and may be a factor in the shorter life expectancy of
      this population compared with white Americans. There is a clear need for improved
      management of hypertension in African Americans via therapeutic lifestyle
      interventions and pharmacotherapy. While there is some evidence that particular
      antihypertensive agent classes provide blood pressure-lowering advantages over
      others, there is no support for withholding agents of any one class. When given
      as monotherapy, diuretics and calcium channel blockers may be relatively more
      effective in lowering blood pressure in African Americans than beta blockers,
      angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers.
      However, when combined with a diuretic, African Americans respond as well to
      these agents as other racial groups. Combination therapy using antihypertensive
      agents with differing modes of action provides additive antihypertensive efficacy
      and is well tolerated. Recent guidelines recommend combination therapy as the
      standard of care for patients with significant blood pressure elevation,
      especially those with diabetes mellitus and renal disease. These comorbidities
      are more common in African Americans and indicate the potential need for initial
      therapy with more than one agent or a combination of agents in one pill.

PMID- 16415638
TI  - Building on the specialist's antihypertensive treatment recommendation: it's just
      the beginning.
AB  - Patients with established cardiovascular disease are a top priority for
      preventive medicine. Evidence from clinical trials supports the merits of
      aggressive risk reduction therapies in survivors of an acute event. Improving
      their cardiovascular risk factor profile prolongs survival, reduces the incidence
      of recurrent atherosclerotic events, and improves quality of life. Blood pressure
      (BP) control is an essential component of cardiovascular disease secondary
      prevention programs; however, many patients are not receiving adequate
      antihypertensive therapy to meet their BP goal. By building on the specialist's
      discharge antihypertensive prescription, primary care physicians are ideally
      positioned to assume responsibility for ensuring BP goals are achieved and
      maintained over the long term in patients who have survived an acute event.
      Current hypertension management guidelines define appropriate BP goals and
      incorporate clear advice on how these goals can be met. BP should be lowered
      slowly and carefully through lifestyle modifications and pharmacologic therapy.
      Antihypertensive treatment should be given according to guidelines for primary
      prevention, although specific antihypertensive classes are indicated for initial
      use in post-myocardial infarction and post-stroke patients. In many cases, BP
      goal attainment will require the use of combination therapy with two or more
      drugs from different classes. With the availability of effective and safe
      antihypertensive drug therapies, including fixed-dose combinations, a BP goal of
      <140/90 mm Hg should be achievable in most patients.

PMID- 16415641
TI  - What is the optimal reperfusion strategy for elderly patients with acute MI?
AB  - The overview of the Fibrinolytic Therapy Trialists' (FTT) Collaborative Group
      showed that, in more than 3000 elderly patients, thrombolytic treatment is
      effective in reducing mortality of patients with acute myocardial infarction with
      ST elevation within 12 hours from the onset of symptoms. Small-scale clinical
      trials confirmed the superiority of primary percutaneous coronary intervention
      even in older patients. However, clinical practice largely differs from the
      setting of clinical trials and, specifically, with respect to primary
      percutaneous coronary intervention. As a consequence, the results observed with
      percutaneous coronary intervention in "real world" patients seem to be less
      favorable than those obtained in trials. For this reason, reperfusion therapy
      with fibrinolytic agents remains the first choice of therapy for ST elevation
      myocardial infarction in the majority of hospitals where direct percutaneous
      coronary intervention facilities are not available.

PMID- 16415639
TI  - Acute coronary artery disease in the elderly: less ventured, less gained.

PMID- 16415640
TI  - Epidemiology, clinical features, and prognosis of acute myocardial infarction in
      the elderly.
AB  - The incidence and prevalence of acute myocardial infarction (MI) increase
      progressively with age. In the United States, over 60% of acute MIs occur in
      patients 65 years of age or older, and approximately one third occur in persons
      over age 75. In addition, mortality rates following acute MI increase
      exponentially with age, such that approximately 60% of all MI deaths in the
      United States occur in the 6% of the population 75 years of age or older. The
      clinical features of acute MI vary by age. In particular, very elderly patients
      are less likely than younger patients to report chest pain. Conversely, confusion
      or altered mental status may be the presenting manifestation of acute MI in up to
      20% of patients over 85 years of age. Older patients are also more likely to have
      "silent" or unrecognized MIs, as well as MIs without ST-segment elevation,
      compared with younger patients. Elderly patients with acute MI are more likely
      than younger patients to experience heart failure, atrial fibrillation, cardiac
      rupture, and shock, all of which are associated with increased mortality. Other
      factors contributing to the poor prognosis following acute MI in elderly
      individuals include a marked decline in cardiovascular reserve in the elderly,
      increased prevalence of comorbid conditions, underutilization of evidence-based
      therapies, and increased risk of iatrogenic complications.

PMID- 16415642
TI  - Primary percutaneous coronary intervention vs. fibrinolytic therapy for acute ST
      elevation myocardial infarction in the elderly.
AB  - Advanced age is associated with worse prognosis among patients with acute ST
      elevation myocardial infarction. Many eligible elderly patients with acute ST
      elevation myocardial infarction, however, do not receive any reperfusion therapy
      at all. The risk of intracranial hemorrhage complicating fibrinolytic therapy
      increases with age. Furthermore, routine adjunctive stenting has made coronary
      angioplasty safer. In total, primary percutaneous coronary intervention is the
      preferred reperfusion strategy among elderly patients with acute ST-elevation
      myocardial infarction, provided that it can be performed without excessive delay.
      The break-even incremental delay with primary percutaneous coronary intervention
      compared with fibrinolytic therapy is not clear at this point and will need to be
      elucidated by future investigation.

PMID- 16415643
TI  - Cardiac rehabilitation in the elderly: patient selection and outcomes.
AB  - In Western countries, the aging and improving survival of patients with coronary
      heart disease are responsible for an increasing number of older adults (65 years
      of age and older) who are eligible for cardiac rehabilitation. The elderly with
      coronary heart disease represent a special population with changes induced by
      aging and lifestyle, comorbidity, cognitive dysfunction, and high risk of
      disability. Although the elderly account for the majority of cardiac admissions
      and procedures, studies on cardiac rehabilitation have traditionally focused on
      younger patients. In aged experimental animals, there is evidence that exercise
      training is able to improve hemodynamic parameters and biologic markers.
      Moreover, in older patients, exercise improves functional capacity and reduces
      myocardial work, similar to that seen in younger patients. As for younger
      patients, cardiac rehabilitation requires a multidisciplinary approach, including
      comprehensive assessment, treatment of risk factors and comorbidity, and
      psychosocial assessment. Cardiac rehabilitation is safe and helpful for elderly
      coronary patients. Physicians must be encouraged to prescribe cardiac
      rehabilitation programs for the elderly following major coronary events and
      coronary revascularization procedures.

PMID- 16415644
TI  - Lifestyle and prevention of cardiovascular disease in the elderly: an Italian
      perspective.
AB  - The life span of human beings is partially influenced by genetic factors, but
      outcomes of aging are profoundly influenced by lifestyle and other environmental
      factors. Age-related modifications of the cardiovascular system are preserved by
      antiaging lifestyle interventions such as physical activity and caloric
      restriction. Accordingly, physical activity and low body mass index reduce
      mortality in older men with cardiovascular diseases. Several mechanisms have been
      proposed to explain the protective effect of lifestyle interventions against
      cardiovascular diseases in the elderly, including a reduction of vulnerability
      (i.e., the age-related reduction of endogenous mechanisms protective against
      pathologic insults). The age-related reduction of ischemic preconditioning, the
      most powerful endogenous protective mechanism against myocardial ischemia, is
      restored by both physical activity and caloric restriction. Thus, older persons
      can implement lifestyle practices that minimize their risk of death from
      cardiovascular diseases.

PMID- 16415645
TI  - Age and comorbidity in acute myocardial infarction: a report from the AMI
      Florence Italian registry.
AB  - A total of 930 cases of ST-segment elevation myocardial infarction were
      prospectively recorded in the Florence health district. Factors influencing
      survival or those associated with use of revascularization (percutaneous coronary
      intervention, 91%) were identified through multivariate analyses (Cox and
      logistic regression, respectively). The independent protective effect of coronary
      reperfusion therapy (CRT) was evident at 36 months (39% reduction in the risk of
      death). After adjusting for all multivariate predictors, CRT use was 63% less
      likely at age 85 years and older than at under 65 years (p<0.001). Since beyond
      advancing age, comorbidity appeared to be associated with a reduced chance of
      CRT, three chronic comorbidity score categories were calculated using information
      on past medical history. Increased 1-year mortality in patients with higher
      comorbidity score categories derives, at least in part, from underutilization of
      CRT. Results confirm that although they might potentially benefit from CRT during
      ST-segment elevation myocardial infarction, older and frail patients are excluded
      from CRT, even when eligible.

PMID- 16415646
TI  - Treatment of non-ST-elevation acute coronary syndrome in the elderly: current
      practice and future opportunities.
AB  - The care of elderly patients with non-ST-elevation acute coronary syndrome is
      challenging, given the wide variability in physiologic condition and preferences
      among this patient group. Due to a higher burden of comorbidity, the elderly face
      high risks for death and complications from non-ST-elevation acute coronary
      syndrome relative to younger patients. Accordingly, they also have greater
      potential benefits from effective therapies. Antithrombotic therapy, invasive
      cardiac care, lipid lowering, and prevention advice, however, are all used less
      often in the elderly, even when no contraindications exist. Attention to
      individualized dosing and safety monitoring is also important for elderly
      patients. Increased awareness of the beneficial impact of therapies on outcomes
      in the elderly, along with vigilance for adverse events, should enable care to
      move from the state of uncertainty to opportunity in this high-risk population.

PMID- 16415648
TI  - Mitral "annular" calcium forming a complete circle "O" causing mitral stenosis in
      association with a stenotic congenitally bicuspid aortic valve and severe
      coronary artery disease.

PMID- 16415647
TI  - A clinical algorithm to differentiate heart failure with a normal ejection
      fraction by pathophysiologic mechanism.
AB  - The incidence and prevalence of heart failure are increasing as the population
      ages. Epidemiologic studies demonstrate that more than half of heart failure
      patients have a normal ejection fraction. The pathophysiology of this disorder is
      not completely understood. It is primarily attributed to left ventricular
      diastolic dysfunction (a leftward- and upward-shifted end-diastolic pressure
      volume relation), where left ventricular diastolic chamber size is normal or
      reduced despite greater-than-normal filling pressures, resulting in reduced
      stroke volume and cardiac output. Using classic measures derived from pressure
      volume analysis, we delineate other possible combinations of the end-systolic and
      end-diastolic pressure-volume relation, and hence possible pathophysiologic
      mechanisms that could underlie the syndrome of heart failure with normal ejection
      fraction. We propose an algorithm for identifying the primary pathophysiologic
      mechanism of heart failure in the setting of a normal ejection fraction using
      three simple factors: blood pressure, electrocardiographic/echocardiographic
      evidence of left ventricular hypertrophy, and left ventricular size. The
      application of this algorithm may aid in guiding management and targeting much
      needed therapies for this population.

PMID- 16415649
TI  - Live/real time three-dimensional transthoracic echocardiographic detection of
      vegetation on a pacemaker/defibrillator lead.

PMID- 16415650
TI  - Pulmonary artery catheters for the management of heart failure.

PMID- 16415654
TI  - I look forward to the challenge of serving as Editor and the arrival of The
      American Journal of the Medical Sciences on our campus.

PMID- 16415651
TI  - Second-degree atrioventricular block and the haystack principle.

PMID- 16415655
TI  - The bird flu conundrum.

PMID- 16415653
TI  - The years during which I have had the privilege of serving as editor of AJMS have
      provided a wonderful experience.

PMID- 16415656
TI  - High prevalence of systemic lupus erythematosus in 78 myasthenia gravis patients:
      a clinical and serologic study.
AB  - OBJECTIVE: The objective of this study was to define the prevalence of systemic
      lupus erythematosus (SLE) in patients with myasthenia gravis (MG). METHODS:
      Seventy-eight MG patients recruited unselectively from Israeli MG database were
      evaluated by medical history, physical examination and serology (ANA at 1:100 and
      anti-ds-DNA at 1:10 dilution) for the presence of SLE, which was defined by the
      presence of four or more American College of Rheumatology diagnostic criteria.
      RESULTS: Thirty-one (40%) of our patients were males and 47 (60%) were females.
      Their mean age at time of the study was 51.5 +/- 14.5 years. Forty patients (51%)
      had an early-onset disease (<40 years); 90% had generalized and 10% had limited
      ophthalmic MG. Significant titers of ANA and ds-DNA autoantibodies were observed
      in 38.5% and 19.2% of the patients. In six (7.7%), a definitive diagnosis of SLE
      was established (MG was first diagnosed; there was no association with previous
      thymectomy), three of them revealed lupus-related neurologic manifestations. All
      six patients were females with an early onset generalized MG. CONCLUSION: High
      prevalence of SLE and lupus-related autoantibodies exist in female MG patients.
      Thus, MG patients should be evaluated for the coexistence of SLE, and assessment
      for MG is suggested in lupus patients with unexplained muscular weakness.

PMID- 16415657
TI  - Postprandial lipemia in postmenopausal women with high fasting high-density
      lipoprotein cholesterol.
AB  - BACKGROUND: Several groups of patients at high risk for cardiovascular disease
      have been found to show an exaggerated postprandial hypertriglyceridemia.
      Postprandial lipemia (PPL) therefore has been implicated as a potential
      additional risk factor that has been evading us. The purpose of this study was to
      test the effect of high fasting high-density lipoprotein cholesterol (HDL-C)
      levels on PPL in postmenopausal females. METHODS: Oral fat tolerance test, as
      quantified by the areas under the curve (AUC) of triglyceride (TG) levels, was
      given to 3 groups: normal postmenopausal females (control), postmenopausal
      females with exceptionally high HDL-C and a familial history of longevity
      (longevity syndrome), and postmenopausal females that were heterozygotes of
      familial hypercholesterolemia (hFH) with exceptionally high HDL-C. RESULTS: The
      PPL was not different between the control and longevity syndrome groups but was
      significantly higher in the hFH group; AUC (SD), in mg/dl/h; 749 (195), 882 (278)
      and 1244 (497) respectively, p=0.002. In linear regression analysis only fasting
      TG levels were a significant predictor of the AUC (Coefficient B = 11.779, p <
      0.001). CONCLUSIONS: In subjects with longevity syndrome the PPL is similar to
      controls, which means that high fasting HDL-C has not any beneficial influence on
      PPL. The fasting TG concentration is the main determinant of PPL. Furthermore,
      postmenopausal females with hFH have higher TG response postprandially, even in
      the case of high fasting HDL-C. Whether there is a threshold below or above,
      where HDL-C becomes a significant independent determinant of PPL is a question to
      be answered by future research.

PMID- 16415658
TI  - Pseudohyperkalemia in patients with increased cellular components of blood.
AB  - OBJECTIVE: We performed a study to investigate the difference between serum and
      plasma potassium concentration in patients with increase in one or more of the
      cellular components of blood. DESIGN AND METHODS: This study was performed in two
      phases. During the first phase, we performed a cross-sectional comparison of the
      difference between serum and plasma potassium concentration (Dk) in 341 patients
      with the various clinical conditions where pseudohyperkalemia has been described,
      as well as with secondary or spurious erythrocytosis and in 30 normal controls. A
      cut-off value of Dk discriminating polycythemia vera from other erythrocytoses
      was estimated. In the second phase we studied the significance of this cut-off
      value as predictor of polycythemia vera in 90 naive patients who were referred
      with an elevated hematocrit. RESULTS: Dk was significantly increased in the
      groups with platelet, erythrocyte or with a mixed type disorder compared to the
      controls (P < 0.01). Among these groups, Dk was significantly increased in the
      groups with thrombocytosis and mixed type disorder, compared to the group with
      erythrocytosis (both P < 0.01). A cut-off value of Dk discriminating polycythemia
      vera from other erythrocytoses was estimated (0.70 mmol/L). Dk (> or = 0.70
      mmol/L), platelet and white blood cell count were identified as significant
      independent predictors of polycythemia vera. CONCLUSIONS: The Dk is increased in
      patients with erythrocytoses, thrombocytoses or both. This phenomenon is more
      profound in patients with a mixed type disorder, such as polycythemia vera
      patients, compared to those with erythrocytoses alone.

PMID- 16415659
TI  - The pharmacist-physician relationship in the detection of ambulatory medication
      errors.
AB  - BACKGROUND: Expenditures on outpatient prescription drugs have increased
      enormously in the last decade. Despite this growth in expenditures, prescription
      medication safety in the ambulatory setting is lacking. Prior research in
      outpatient care has centered around the physician-patient encounter. What remains
      unexamined in the ambulatory care literature is the pharmacist's role as
      interceptor, detector, and reporter of medication errors to the physician.
      METHODS: Data about the role, responsibilities, and expectations to inform
      physicians about this subject were collected from pharmacist (N = 30) and patient
      (N = 31) focus groups conducted between July 2002 and July 2003. Pharmacists in
      outpatient practices and patients were randomly selected from the state licensure
      database and the Jackson Metropolitan phonebook, respectively. ANALYSIS: Grounded
      theory provided the perspective on which data were interpreted. Data patterns
      were linked using key words and phrases for theme analysis. Arbitration between
      coders resulted in an inter-rater reliability of 0.85. RESULTS: : Three
      complementary patterns were identified from the data: 1) patients likely see
      multiple physicians and only one pharmacist; 2) patients are more likely to
      report medication errors to the pharmacist than to the physician; and 3)
      pharmacists are the final interceptors, detecting medication errors before they
      reach patients. CONCLUSIONS: Ambulatory pharmacists are in a privileged position
      to gather data regarding adverse responses to prescribed medication or incidents
      of medication mishaps. The failure of pharmacists to report information back to
      physicians is a missed opportunity to improve patient safety.

PMID- 16415661
TI  - Secondary hyperparathyroidism in patients with untreated and treated congestive
      heart failure.
AB  - BACKGROUND: The congestive heart failure syndrome includes a systemic illness
      with wasting of soft tissues and bone. We hypothesized secondary
      hyperparathyroidism (HPT) would be found in hospitalized patients with
      decompensated congestive heart failure (CHF), where secondary aldosteronism is
      expected, and who were either untreated or treated medically. METHODS: In 9
      consecutive patients (7 males, 2 females; 8 African-American, 1 Caucasian; 33-60
      yrs) admitted to the Regional Medical Center during a 28-day period with chronic
      left ventricular systolic dysfunction (EF<35%) and decompensated CHF (5
      untreated; 4 treated with an angiotensin converting enzyme inhibitor, furosemide,
      and small-dose spironolactone), we measured: plasma parathyroid hormone (PTH);
      serum calcium corrected for albumin, magnesium, and phosphorus; serum creatinine
      and calculated creatinine clearance. RESULTS: Plasma PTH was elevated above the
      normal range (6-65 pg/mL) in both untreated and treated patients with CHF (204+/
      60 and 134+/-14 pg/mL, respectively). Serum corrected calcium was normal (8.4
      10.2 mg/dL) in both untreated and treated CHF (9.7+/-0.l and 9.1+/-0.2 mg/dL,
      respectively) as were serum magnesium and phosphorus. Calculated creatinine
      clearance did not differ between untreated and treated patients (74+/-15 and 83+/
      21 mL/min, respectively). CONCLUSIONS: Secondary HPT was found in 5 untreated and
      4 treated patients consecutively hospitalized over a 28-day period with
      decompensated CHF. Corrected serum calcium was normal. Plasmaionized calcium, a
      determinant of PTH secretion, was not measured. Although vitamin D levels were
      not assessed, the presence of hypovitaminosis D in these housebound patients with
      symptomatic CHF cannot be discounted. HPT may contribute to the systemic illness
      that accompanies CHF, including bone wasting.

PMID- 16415660
TI  - The prevalence and prognosis of a Brugada-type electrocardiogram in a population
      of middle-aged Japanese-American men with follow-up of three decades.
AB  - BACKGROUND: The Brugada syndrome is an inherited arrhythmogenic and nonstructural
      heart disease associated with an increased risk of sudden cardiac death from
      ventricular fibrillation. There are conflicting data about its prevalence and
      prognosis. Particularly, population-based studies are lacking in the United
      States and other countries. METHODS: A total of 8006 Japanese-American men aged
      45 to 68 years participated in the initial examination of the Honolulu Heart
      Program during the period of 1965 through 1968. After excluding prevalent cases
      with coronary heart disease, 864 electrocardiograms coded as right bundle branch
      block were reviewed using the specified criteria for Brugada-type
      electrocardiogram. Baseline characteristics and the prognosis of Brugada-type
      electrocardiogram were compared with 5983 control subjects who had
      electrocardiograms coded as normal at the initial examination. RESULTS: There
      were 12 typical cases and 11 atypical cases of Brugada-type electrocardiogram at
      the initial examination (prevalence, 0.15% and 0.14%, respectively). Analysis of
      baseline characteristics revealed no difference between control cases and either
      typical or atypical Brugada-type electrocardiogram cases except significantly
      lower body mass index in subjects with Brugada-type electrocardiogram. During the
      30-year follow-up period, none of the subjects died suddenly within 24 hours
      after the onset of symptoms. Survival analysis revealed no significant difference
      between case and control groups. CONCLUSIONS: Brugada-type electrocardiograms
      among middle-aged or elderly Japanese-American men are uncommon and are not
      associated with increased risk of either sudden death or total mortality.

PMID- 16415662
TI  - A case of acute hypersensitivity pneumonitis associated with an oil fan heater.
AB  - We report here a case of acute hypersensitivity pneumonitis induced by an oil fan
      heater. A 57-year-old man was admitted to our hospital because of fever,
      nonproductive cough, and dyspnea. Paeccilomyces variotii and Paeccilomyces nivea
      were identified from an oil fan heater in his house. The result of an
      environmental challenge test was positive. Intradermal reaction and precipitin
      results to sugar antigen of those fungi were positive only in the patient. This
      is the first described case of acute hypersensitivity pneumonitis caused by an
      oil fan heater.

PMID- 16415663
TI  - Recurrent hyponatremia after intrathecal methotrexate not related to antidiuretic
      hormone: is a natriuretic peptide activated?
AB  - We report the development of recurrent hyponatremia after intrathecal
      methotrexate that was not associated with elevated levels of antidiuretic
      hormone. We speculate that a central nervous system natriuretic peptide may be
      involved in the pathogenesis of the naturesis following intrathecal methotrexate.

PMID- 16415664
TI  - Acute cytomegalovirus infection associated with the onset of inflammatory bowel
      disease.
AB  - A 29-year-old man was admitted with high-grade fever, crampy abdominal pain, and
      watery diarrhea that had persisted for 2 weeks before his admission. Symptomatic
      treatment (acetaminophen only) was of no benefit. On physical examination, there
      was diffuse abdominal tenderness. Laboratory tests showed a leukomoid reaction
      with atypical lymphocytosis, and serology tests revealed acute cytomegalovirus
      infection. Abdominal computed tomography and colonoscopy revealed an inflammatory
      process involving the large intestine. On histologic examinations of intestinal
      biopsy samples, there was an active inflammation with no inclusion bodies. The
      patient was treated with ganciclovir with only mild improvement. Adding 5
      aminosalicylic acid caused little further improvement. Repeated colonoscopy
      performed 2 months later showed severe chronic ulcerative colitis. Only the
      addition of systemic steroids caused complete resolution of the symptoms. On
      review of the literature (Medline search for cytomegalovirus colitis in
      immunocompetent patients), 18 cases were found. On follow-up, 10 of these
      patients were found to have inflammatory bowel disease.

PMID- 16415665
TI  - Central nervous system infection caused by Morganella morganii.
AB  - Central nervous system (CNS) infection with Morganella morganii is very rare. We
      describe a 38-year-old female patient with frontal brain abscess caused by M
      morganii who was unsuccessfully treated. We also review all reported cases of
      Morganella CNS infections with an emphasis on treatment modalities and outcomes.
      Aggressive surgical management and appropriate antimicrobial therapy can lead to
      cure, but the mortality rate for these infections remains high.

PMID- 16415666
TI  - Ehlers-Danlos type IV syndrome in a patient with Down syndrome: simple co
      occurrence or true association?
AB  - Down syndrome, a common chromosome aneuploidy, has been associated with an
      increased incidence of cutaneous disorders. The simultaneous occurrence with
      Ehlers-Danlos syndrome (EDS) is rare. We report here the clinical case of a 19
      year-old female patient with Down syndrome (trisomy 21) who was also affected by
      EDS type IV. She died from spontaneous bleeding due to rupture of nonaneurysmal
      abdominal aorta. Since the affected chromosomes in these two syndromes are
      different (21 and 2, respectively), the concomitant appearance of Down syndrome
      and EDS type IV in our patient, though clinically intriguing, most likely
      represents a co-occurrence. However, the possibility that a presently unknown
      link may exist between these syndromes cannot be ruled out.

PMID- 16415667
TI  - Abdominal Castleman disease with mixed histopathology in a patient with iron
      deficiency anemia, growth retardation and peliosis hepatis.
AB  - In Castleman disease, also known as giant lymph node hyperplasia, lesions are
      usually located in the chest. Peliosis hepatis is the presence of multiple blood
      filled cysts in the liver. The combination of these two disorders in one patient
      is rare, with only three cases reported to date. We report the case of a 21-year
      old man who presented with growth retardation and iron deficiency anemia. Work-up
      revealed hepatomegaly and multiple conglomerated giant lymph nodes near the
      splenic hilum. Once the mass was surgically removed, the patient's anemia rapidly
      resolved and he showed catch-up growth. The lymphoid tissue exhibited mixed
      histologic type, so the patient was diagnosed with both hyaline vascular type and
      plasma cell type Castleman disease. A liver biopsy obtained at surgery showed
      sinusoidal dilatation and blood-filled cysts, indicating peliosis hepatis. This
      is the fourth documented case of peliosis hepatis associated with Castleman
      disease. In addition to describing the case features, we discuss the possible
      pathogenesis of peliosis hepatis in the setting of Castleman disease.

PMID- 16415668
TI  - Metformin-associated lactic acidosis precipitated by acute renal failure.
AB  - Metformin-associated lactic acidosis (MALA) is a rare but serious clinical
      entity. It is almost always seen in patients with a serious underlying medical
      disorder, most often a degree of renal impairment or other factors that are known
      to predispose to the lactic acidosis. We report a case of MALA in which acute
      renal failure resulting from hypovolemia secondary to acute gastroenteritis
      likely precipitated the condition. Early recognition of this condition and
      initiation of treatment are important. Bicarbonate hemodialysis is the treatment
      of choice.

PMID- 16415670
TI  - Sudden deafness.

PMID- 16415672
TI  - Hemispatial neglect, balance and eye-movement control.
AB  - PURPOSE OF REVIEW: Disorders of spatial awareness and balance following stroke
      are common but often under-diagnosed. They lead to poor outcome and frequently
      coexist. Here we focus on recent progress in the understanding of the mechanisms
      underlying these disorders and potential therapeutic advances. RECENT FINDINGS:
      Right-hemisphere networks are important for both spatial attention and postural
      awareness. Neglect patients show multiple oculomotor impairments including
      reduced saccade amplitude and difficulty retaining spatial locations across
      saccades. There has been controversy regarding the brain regions associated with
      neglect, although most studies show the right inferior parietal lobe to be
      crucial and new imaging modalities have provided insight into neglect caused by
      subcortical stroke. The 'pusher syndrome' is a poorly understood balance disorder
      where patients push towards their paretic side, resulting in falls. It may
      involve impairment of subjective verticality but experimental studies have
      reported diverse findings. Advances in treatment for neglect include the
      successful use of prism adaptation and pilot data suggesting noradrenergic
      stimulation may improve search in selected patients. SUMMARY: New experimental
      techniques have provided insight into the debilitating disorders of spatial and
      postural awareness that often follow stroke. There are currently no widely used
      therapies for neglect but both new behavioural techniques and pharmacological
      methods are promising.

PMID- 16415673
TI  - Function tests of the otolith or statolith system.
AB  - PURPOSE OF REVIEW: This review aims to provide an overview of recent advances in
      tests to evaluate otolith function over the last 2 years. RECENT FINDINGS: Over
      the last 2 years, many papers have focused on the application of the vestibular
      evoked myogenic potentials (VEMP). Several aspects are under survey: a search for
      optimal stimuli, search for normative data, search for which labyrinthine
      function losses and what kind of pathologies induce abnormal VEMPs. The review
      shows that some fundamental problems still have to be solved to improve
      reproducibility and to increase sensitivity. Other research and modelling is
      performed to find out how the brain distinguishes tilts from translations.
      Several papers support routine implementation of subjective visual vertical (SVV)
      measurements (in rest and during centrifugation) in the standard vestibular test
      battery. Interesting reports mention short latency vestibulo-ocular reflex
      induced by taps and short auditory stimuli. One report mentions the impact of
      otolith dysfunction upon spontaneous nystagmus and head shaking nystagmus.
      SUMMARY: Although validation is still needed and in progress, the state of the
      art laboratory should consider the following tests for an evaluation of otolith
      function as relevant: slow tandem gait, VEMP, SVV during centrifugation.

PMID- 16415671
TI  - Current concepts of mechanical and neural factors in ocular motility.
AB  - PURPOSE OF REVIEW: The oculomotor periphery was classically regarded as a simple
      mechanism executing complex behaviors specified explicitly by neural commands. A
      competing view has emerged that many important aspects of ocular motility are
      properties of the extraocular muscles and their associated connective tissue
      pulleys. This review considers current concepts regarding aspects of ocular
      motility that are mechanically determined versus those that are specified
      explicitly as innervation. RECENT FINDINGS: While it was established several
      years ago that the rectus extraocular muscles have connective tissue pulleys,
      recent functional imaging and histology has suggested that the rectus pulley
      array constitutes an inner mechanism, analogous to a gimbal, that is rotated
      torsionally around the orbital axis by an outer mechanism driven by the oblique
      extraocular muscles. This arrangement may account mechanically for several
      commutative aspects of ocular motor control, including Listing's Law, yet permits
      implementation of non-commutative motility. Recent human behavioral studies, as
      well as neurophysiology in monkeys, are consistent with implementation of
      Listing's Law in the oculomotor periphery, rather than centrally. SUMMARY: Varied
      evidence now strongly supports the conclusion that Listing's Law and other
      important ocular kinematics are mechanically determined. This finding implies
      more limited possibilities for neural adaptation to some ocular motor
      pathologies, but indicates possibilities for surgical treatments.

PMID- 16415674
TI  - Immune-mediated inner-ear disorders in neuro-otology.
AB  - PURPOSE OF REVIEW: Immune-mediated inner-ear disorders may present to different
      medical disciplines and new research findings emerge rapidly. The purpose of this
      review is to draw the different strands together to produce an overview
      describing the clinical presentation of immune-mediated inner-ear disorders and
      to discuss useful diagnostic criteria with a focus on tissue-specific and tissue
      non-specific antibodies. RECENT FINDINGS: The importance of diagnosing an immune
      mediated inner-ear disorder is highlighted in the context of it being one of few
      forms of treatable inner-ear disorder with a good response to immunosuppressive
      therapy. Due to a lack of reliable tests, the criteria upon which the diagnosis
      of immune-mediated inner-ear disease is based are often arbitrary. Previous and
      current research focuses mainly on the investigation of the aetiology of immune
      mediated disorders, studying the presence of autoantibodies and the antigens
      responsible for their production. The prognostic and therapeutic values of inner
      ear-specific antibodies are still unclear. Various antigens have been suggested.
      However, most antigens identified have been ubiquitous proteins not specific to
      the inner ear and therefore lack logical association with localized inner-ear
      pathology. SUMMARY: Early diagnosis of immune-mediated inner-ear disorders with
      prompt treatment may prevent irreversible damage to inner-ear structures.
      Accordingly, it is important to include immune-mediated inner-ear disorders in
      the differential diagnosis of patients presenting with 'idiopathic'
      audiovestibular dysfunction. To enable early diagnosis, we recommend that the
      current available routine immunological laboratory tests (antinuclear,
      antineutrophil cytoplasmic, antiendothelial cell,
      antiphospholipid/anticardiolipin and antithyroid antibodies) are used when
      assessing a patient with suspected immune-mediated inner-ear disorder.

PMID- 16415675
TI  - Pharmacological advances in the treatment of neuro-otological and eye movement
      disorders.
AB  - PURPOSE OF REVIEW: First, to describe the current pharmacological treatment
      options for peripheral and central vestibular, cerebellar, and ocular motor
      disorders. Second, to identify vestibular and ocular motor disorders in which
      treatment trials are warranted. RECENT FINDINGS: Peripheral vestibular disorders:
      In vestibular neuritis recovery of the peripheral vestibular function can be
      improved by treatment with oral corticosteroids. In Meniere's disease treatment
      strategies range from low-salt diet, diuretics, and betahistine, to intratympanic
      injection of corticosteroids or gentamicin. Unfortunately most of the trials on
      Meniere's disease do not have an up-to-date design. In bilateral vestibulopathy
      steroids do not seem to improve vestibular function.Central vestibular,
      cerebellar, and ocular motor disorders: The use of aminopyridines introduced a
      new therapeutic principle in the treatment of downbeat and upbeat nystagmus and
      episodic ataxia type 2 (EA2). These potassium channel blockers presumably
      increase the activity and excitability of cerebellar Purkinje cells, thereby
      augmenting the inhibitory influence of these cells on vestibular and cerebellar
      nuclei. A few studies showed that baclofen improves periodic alternating
      nystagmus, and gabapentin and memantine, pendular nystagmus. Many other eye
      movement disorders, however, such as ocular flutter, opsoclonus, central
      positioning, or see-saw nystagmus are still difficult to treat. SUMMARY: Although
      progress has been made in the treatment of vestibular neuritis, downbeat and
      upbeat nystagmus, as well as EA2, state-of-the-art trials must still be performed
      on many vestibular and ocular motor disorders, namely Meniere's disease,
      bilateral vestibulopathy, vestibular paroxysmia, vestibular migraine, and many
      forms of central eye movement disorders.

PMID- 16415677
TI  - Disability and rehabilitation in the dizzy patient.
AB  - PURPOSE OF REVIEW: This review focuses on prospective studies of vertigo and
      balance therapy in the past 3 years, including advances in vertigo-habituation
      exercises for adults, pediatric intervention, and virtual reality techniques,
      and, in more depth, the literature pertinent to driving motor vehicles. RECENT
      FINDINGS: Increased support has been generated for the efficacy of a minimal,
      home-based vertigo-habituation program for adults with peripheral vestibular
      disorders. Vestibular rehabilitation has been shown to be associated with
      improvements in independence and dynamic visual acuity. Community-based
      vestibular rehabilitation has been shown to be efficacious for selected patients,
      after careful screening, when trained personnel provide intervention. Vestibular
      rehabilitation has been incorporated into the rehabilitation program for head
      injured military personnel who will be returned to duty, and multifactorial
      balance rehabilitation has been shown to be useful for children with hearing and
      balance impairments. Virtual reality techniques have made significant advances,
      so immersive environments have potential for rehabilitation for patients with
      vestibular disorders and for developing training regimens for astronauts to
      ameliorate some effects of exposure to microgravity. Driving skill, in general,
      is affected by use of benzodiazepines. For many patients with vestibular
      impairments driving is a particularly problematic activity of daily living.
      SUMMARY: Progress has been made in studies of acute care, community-based, and
      pediatric vestibular rehabilitation. Work on simulator-based paradigms has moved
      toward readiness for implementation. Studies of driving have provided some
      insight into the problems of these patients. More work remains to be done on all
      of these problems.

PMID- 16415676
TI  - Chronic dizziness: the interface between psychiatry and neuro-otology.
AB  - PURPOSE OF REVIEW: This paper reviews the often-enigmatic relationships between
      dizziness and psychiatric symptoms. Psychiatric causes of dizziness, neuro
      otologic causes of anxiety, underrecognized co-morbid conditions, and medical
      illnesses that masquerade as 'psychogenic' dizziness are examined. Key clinical
      features and data from recent treatment trials are presented with potential
      pathophysiologic mechanisms. RECENT FINDINGS: Investigations at the interface
      between psychiatry and neuro-otology have identified the distinguishing features
      of several clinical conditions that present with non-vertiginous dizziness,
      subjective imbalance, and psychiatric symptoms. The most common condition is
      chronic subjective dizziness; a refinement of earlier concepts of psychogenic
      dizziness, phobic postural vertigo, and space-motion phobia. Chronic subjective
      dizziness is consistent with advancing research on anxiety and somatoform
      disorders and offers greater insights into the relationships between neuro
      otologic illnesses and anxiety. Migraine, post-concussional syndrome, and
      dysautonomias also cause persistent dizziness and may be misdiagnosed or
      malingering or psychogenic dizziness because they often present with comorbid
      psychiatric symptoms in the absence of identifiable vestibular deficits. SUMMARY:
      Recent research has defined the key features of several medical-psychiatric
      conditions that cause chronic dizziness, permitting greater diagnostic precision
      and insight into underlying pathophysiologic processes. Treatment studies have
      identified potentially effective interventions, which must be evaluated in
      controlled clinical trials.

PMID- 16415678
TI  - Cerebral small vessel diseases: manifestations in young women.
AB  - PURPOSE OF REVIEW: Cerebral small vessel diseases are responsible for 20-30% of
      ischemic strokes as well as for a considerable proportion of cerebral hemorrhages
      and encephalopathies. Less known than the manifestations in old age are those in
      young women comprising posterior encephalopathy and Susac's syndrome. RECENT
      FINDINGS: Magnetic resonance imaging has allowed us to identify posterior
      encephalopathy, characterized by headache, seizures, visual disturbances and
      hypertension, as a frequent complication of preeclampsia/eclampsia syndrome in
      the perinatal and postpartum period. Magnetic resonance findings are
      pathognomonic with bilateral cortical-subcortical lesions in the posterior
      hemispheres typically sparing the calcarine fissure. Conversely, white matter
      lesions on magnetic resonance imaging particularly involving the corpus callosum,
      and a (subclinical) sensorineural hearing loss are diagnostic of the
      retinocochleocerebral vasculopathy called Susac's syndrome. SUMMARY: Posterior
      encephalopathy can also follow from a broad spectrum of endotheliotoxic
      conditions like chemotherapy, immunosuppression and sepsis. Early recognition of
      the disorder is decisive for a benign outcome since therapy consists of removal
      of precipitating factors, lowering of blood pressure and treatment with magnesium
      sulfate. The retinocochleocerebral vasculopathy appears to be underdiagnosed. An
      autoimmune-mediated arteriolopathy is presumed and the disease is nearly always
      monophasic. A variety of therapeutic approaches have been recommended, none of
      which, however, is based on anything other than anecdotal evidence.

PMID- 16415680
TI  - Spinal dural arteriovenous fistula.
AB  - PURPOSE OF REVIEW: To summarize clinical key points, diagnostic features, and
      results of imaging and therapy of spinal dural arteriovenous fistula (SDAVF).
      RECENT FINDINGS: SDAVF accounts for 70% of spinal arteriovenous malformation with
      an annual incidence of 5-10 cases per million. At least 80% of patients are male,
      and more than 66% of patients are in the sixth and seventh decade of life
      indicating preponderance of gender and age. Thrombophilia is not a predisposing
      factor of disease. Clinical course is predominated by symptoms of congestive
      myelopathy, but subarachnoid hemorrhage may occur. Double SDAVF is a rare problem
      in the management of disease. Magnetic resonance imaging has replaced myelography
      as screening procedure. Contrast-enhanced magnetic resonance angiography and
      multislice computerized tomographic angiography may facilitate diagnostic
      procedure, however, spinal angiography is still required to confirm diagnosis.
      Treatment by permanent occlusion of fistula results in clinical improvement in
      70% of cases. Microsurgical shunt interruption has proven secure and reliable.
      Endovascular shunt embolization has been established as a standardized procedure,
      but occlusion rates are still lower than in surgical treatment. SUMMARY: Advances
      have been made in diagnosis and treatment of SDAVF, but the disease is still not
      completely understood.

PMID- 16415679
TI  - Invasive treatment of unruptured brain arteriovenous malformations is
      experimental therapy.
AB  - PURPOSE OF REVIEW: Brain arteriovenous malformations (AVMs) are currently being
      treated in a variety of ways, including medical management, endovascular
      procedures, neurosurgery and radiotherapy. The widespread diffusion of these
      various treatment approaches is partially driven by the existence of variations
      in the perception about the risks of rupture, and how devastating such events
      would be. RECENT FINDINGS: Data from the most recent studies suggest the majority
      of AVM patients are diagnosed without signs of hemorrhage, further, that the
      natural history risk for the unruptured cohort is far more benign than for those
      presenting with rupture. In cases where hemorrhage occurs, the clinical syndrome
      is significantly less disabling than in patients with non-AVM related hemorrhage.
      For unruptured AVMs, current morbidity data suggest a higher risk for invasive
      management than for the natural history of untreated patients. SUMMARY: No
      randomized clinical trial data exist on the benefit of invasive AVM treatment,
      and the most contentious issue at present is whether intervention should be
      considered for AVMs that have not bled. In a scientific sense, invasive treatment
      for unruptured brain AVMs may be considered experimental therapy awaiting the
      results from 'A Randomized Trial of Unruptured Brain AVMs' (ARUBA), which is
      currently underway.

PMID- 16415681
TI  - Mechanisms of recovery in stroke patients with hemiparesis or aphasia: new
      insights, old questions and the meaning of therapies.
AB  - PURPOSE OF REVIEW: The mechanisms responsible for recovery after stroke in
      patients with hemiparesis or aphasia are under intense study, since knowledge of
      these mechanisms is a prerequisite for choosing which therapy a patient receives
      and when to apply it. RECENT FINDINGS: Most of the recent insights are obtained
      with longitudinal studies using functional imaging and direct cortical
      stimulation during the process of recovery. They reveal that reorganization is a
      highly dynamic process, involving the establishment of new communications in the
      remaining system and showing similarities to learning processes in healthy
      individuals. Lesion localization is a major determinant for recovery and the
      pattern of reorganization. Neurobiological hypotheses lead to clinical studies,
      which in turn are now used to confirm or reject these hypotheses. SUMMARY:
      Although our understanding of the mechanisms responsible for recovery is
      increasing, the application of this knowledge in daily praxis is still limited. A
      better understanding of the underlying mechanisms, however, can lead to
      appropriate therapies for individual patients.

PMID- 16415682
TI  - Motor learning: its relevance to stroke recovery and neurorehabilitation.
AB  - PURPOSE OF REVIEW: Much of neurorehabilitation rests on the assumption that
      patients can improve with practice. This review will focus on arm movements and
      address the following questions: (i) What is motor learning? (ii) Do patients
      with hemiparesis have a learning deficit? (iii) Is recovery after injury a form
      of motor learning? (iv) Are approaches based on motor learning principles useful
      for rehabilitation? RECENT FINDINGS: Motor learning can be broken into kinematic
      and dynamic components. Studies in healthy subjects suggest that retention of
      motor learning is best accomplished with variable training schedules. Animal
      models and functional imaging in humans show that the mature brain can undergo
      plastic changes during both learning and recovery. Quantitative motor control
      approaches allow differentiation between compensation and true recovery, although
      both improve with practice. Several promising new rehabilitation approaches are
      based on theories of motor learning. These include impairment oriented-training
      (IOT), constraint-induced movement therapy (CIMT), electromyogram (EMG)-triggered
      neuromuscular stimulation, robotic interactive therapy and virtual reality (VR).
      SUMMARY: Motor learning mechanisms are operative during spontaneous stroke
      recovery and interact with rehabilitative training. For optimal results,
      rehabilitation techniques should be geared towards patients' specific motor
      deficits and possibly combined, for example, CIMT with VR. Two critical questions
      that should always be asked of a rehabilitation technique are whether gains
      persist for a significant period after training and whether they generalize to
      untrained tasks.

PMID- 16415683
TI  - Bibliography. Current world literature. Neuro-ophthalmology and neuro-otology.

PMID- 16415684
TI  - Severe Pseudomonas aeruginosa keratitis shortly after initiation of corneal
      refractive therapy.
AB  - PURPOSE: To report the development of severe ulcerative keratitis in an
      adolescent, shortly after initiating corneal refractive therapy. METHODS: A
      teenager developed severe ulcerative keratitis shortly after being fitted with
      reverse-geometry contact lenses. The contact lenses were worn daily and only one
      night before the occurrence of severe ulcerative keratitis. Pseudomonas
      aeruginosa was identified as the causative organism. RESULTS: The patient was
      treated with intensive, fortified antibiotics with gradual resolution of the
      corneal ulcer, leaving a permanent central stromal scar. CONCLUSIONS: Corneal
      refractive therapy contact lenses can cause severe bacterial keratitis even after
      a short wearing time. Significant caution should be used before prescribing
      corneal refractive therapy lenses, and informed consent should include potential
      sight-threatening infectious keratitis.

PMID- 16415686
TI  - The effect of multipurpose solutions on the ocular surface.
AB  - PURPOSE: We aimed to determine if multipurpose contact lens solutions could
      solely contribute to adverse ocular surface effects. Three specific multipurpose
      solutions were evaluated: Bausch & Lomb ReNu MultiPlus (ReNu with MoistureLoc was
      not evaluated in this study), Alcon No Rub Opti-Free Express, and Advanced
      Medical Optics Complete Moisture Plus. The impact that solutions have on the
      ocular surface, if negative, could be adverse. Nearly all recent studies examine
      the effects of solutions through the contact lens as a vehicle for delivery. The
      lens itself cannot be completely ruled out as a causal factor. METHODS: 21
      subjects were randomized to one of the three solution groups. Subjects self
      administered a solution to their treatment eye four times daily, with the fellow
      eye serving as the control. Solutions and the test eye were masked to the subject
      and examiner. A battery of ocular surface testing was conducted at the baseline
      examination and at every week interval by masked examiner. RESULTS: Non
      parametric data was analyzed by Friedman 1-way ANOVA and parametric data by the 1
      way repeated measures ANOVA. A reduction in tear breakup time was found to be
      statistically significant for the ReNu group (P < 0.05). CONCLUSIONS: ReNu has
      frequently been cited as being more cytotoxic. We propose that when used at a
      high frequency, ReNu preservatives and additives are adverse. Contact lens
      dropout and/or clinical signs noted by the examiner may be linked to the use of
      ReNu.

PMID- 16415685
TI  - Bcl-2 and Bax regulation of corneal homeostasis in genetically altered mice.
AB  - PURPOSE: The antiapoptotic protein Bcl-2 and its proapoptotic counterpart Bax may
      play an important role in the regulation of corneal epithelial renewal. To
      understand the physiologic importance of Bcl-2 and Bax in the healthy cornea,
      epithelial and stromal thickness, proliferation, and surface cell exfoliation
      rates were examined in the central cornea of genetically altered mice
      overexpressing Bcl-2 and lacking Bax. METHODS: Adult Bcl-2 transgenic (n = 55)
      and Bax knockout (n = 82) mice and wild-type controls were clinically prescreened
      at no less than 2 months of age for any ocular developmental abnormalities.
      Polymerase chain reaction was used to confirm genotype. Corneal epithelial
      renewal was examined by in vivo tandem scanning confocal microscopy to measure
      total corneal and sublayer thickness and by immunohistochemistry on whole mount
      corneal tissues to determine basal epithelial cell proliferation using 5-bromo-2
      deoxyuridine (BrdU) and surface cell exfoliation with a Calcein AM-Ethidium
      homodimer assay (live/dead). Stained corneas were scanned with a laser scanning
      confocal microscope, and images were digitized, and cell counts were obtained.
      Levels of Bcl-2 protein were assessed by Western blots. RESULTS: No significant
      changes in proliferation or cell death were found in either group compared to
      wild-type littermate controls; however, epithelial and stromal thicknesses were
      greater in the Bcl-2 transgenic group compared to wild-type and decreased in the
      Bax knockout. Western blotting confirmed that there was no change in the level of
      Bcl-2 expression in the corneal epithelium in the Bcl-2 transgenic or Bax
      knockout strains. CONCLUSIONS: The significant difference in epithelial and
      stromal thickness suggests a functional role for Bcl-2 and Bax in the maintenance
      of corneal homeostasis; however, the lack of significant alterations in
      proliferation, cell exfoliation, and levels of Bcl-2 protein in the adult corneal
      epithelium suggest that these phenotypic changes are a result of a new stable
      homeostatic equilibrium (proliferation + migration = shedding). Additional
      experiments to delineate the role of Bcl-2 and Bax during development and in the
      adult cornea are necessary.

PMID- 16415689
TI  - An evaluation of the efficacy of a cyclosporine-based dry eye therapy when used
      with marketed artificial tears as supportive therapy in dry eye.
AB  - PURPOSE: To evaluate the efficacy of marketed artificial tears in relieving the
      signs and symptoms of dry eye when used as supportive therapy to a cyclosporine
      based ophthalmic emulsion. METHODS: Sixty-one patients were enrolled in this
      randomized, investigator-masked, parallel study of 6 months' duration. Eligible
      patients needed a Schirmer I score without anesthesia of 7 mm or less at day -7
      and to answer that they needed artificial tears at least "some of the time."
      Corneal staining of 3 or more (National Eye Institute grid, 15 points) at day -7
      and day 0 in the same eye was also required. Patients were randomized to one of
      three regimens: Restasis (0.05% cyclosporine) twice per day with Systane used a
      minimum of once per day (Restasis + Systane); Restasis twice per day with Refresh
      Tears used a minimum of once per day (Restasis + Refresh); and Systane alone used
      four times per day. Signs and symptoms were measured at days -7, 0, 7, 14, 28,
      42, 120, and 180. RESULTS: A statistical difference was seen in favor of Restasis
      + Systane versus Restasis + Refresh for corneal staining (P = 0.0048) change from
      baseline and a trend (P = 0.0725) for increased tear film breakup time at 6
      months. There were no differences between treatment groups for Schirmer score,
      conjunctival staining, or conjunctival injection. Significant differences were
      seen in favor of Restasis + Systane versus Restasis + Refresh for less ocular
      burning (P = 0.0210), stinging (P = 0.0314), grittiness (P = 0.0128), and dryness
      (P = 0.0132). Systane was better than Restasis + Refresh for less burning (P =
      0.0288), dryness (P = 0.0480), and scratchiness (P = 0.0294). CONCLUSIONS:
      Results indicate that the choice of concomitant therapy used with Restasis has
      significant effects on outcome measures. Both supportive therapies were
      compatible with Restasis.

PMID- 16415690
TI  - Combining central and peripheral videokeratoscope maps to investigate total
      corneal topography.
AB  - PURPOSE: To extend the area of standard corneal topography maps, one central map
      is combined with six peripheral maps after correlating them in a custom written
      computer program. METHODS: The point corresponding to the vertex normal of the
      central map is found in each of the peripheral maps. Data from the peripheral
      maps can then be added on to the edges of the central map to create a topography
      map that extends from limbus to limbus horizontally and vertically. RESULTS: The
      average size of the combined maps from 15 subjects was 11.3 +/- 0.3 mm
      horizontally and 10.3 +/- 0.3 mm vertically, compared to 9.2 +/- 0.4 mm
      horizontally and 7.5 +/- 0.7 mm vertically for the standard single maps. These
      values represent an increase in surface area of approximately 70%. CONCLUSIONS:
      The topography of the entire cornea can be represented by combining multiple
      measurements from a Placido videokeratoscope. Conic fits based on central
      topography data are a poor representation of the total corneal shape.

PMID- 16415688
TI  - Daytime orthokeratology associated with infectious keratitis by multiple gram
      negative bacilli: Burkholderia cepacia, Pseudomonas putida, and Pseudomonas
      aeruginosa.
AB  - PURPOSE: To report a case of a corneal ulcer in a patient who wore
      orthokeratology contact lenses during the day. METHODS: Case report. RESULTS: A
      16-year-old girl who underwent orthokeratology treatment developed a corneal
      ulcer in her right eye. The refractive status of the affected eye was -5.75 -1.75
      x 180, and the best-corrected visual acuity was 20/40. Corneal topography showed
      the temporal upper dislocation of a central flattened zone in the right eye. The
      patient had worn orthokeratology contact lenses during the day for more than 4
      years. Her ulcer became worse after treatment with tobramycin and gentamicin for
      1 day. After treatment with ciprofloxacin, the ulcer healed, and visual acuity
      returned to 20/20 with spectacle correction. Cultures of the cornea, contact
      lens, and lens solution all grew Burkholderia cepacia, Pseudomonas putida, and
      Pseudomonas aeruginosa. CONCLUSIONS: Improper fitting of lenses and contamination
      of lenses or solutions in orthokeratology therapy are risk factors for a corneal
      ulcer, even when patients wear orthokeratology lenses only during the day.

PMID- 16415691
TI  - Use of intralimbal rigid gas-permeable lenses for pellucid marginal degeneration,
      keratoconus, and after penetrating keratoplasty.
AB  - PURPOSE: To discuss the results of fitting Dyna Intra-Limbal lenses (Lens
      Dynamics, Inc., Golden, CO) (DIL) for pellucid marginal degeneration (PMD),
      keratoconus, and after penetrating keratoplasty (PK). METHODS: The charts of
      patients fitted with DILs between January 2003 and December 2004 were
      retrospectively reviewed. Ocular diagnosis, indication for DIL, flat and steep
      curvatures by corneal topography, and age at the time of initial fitting were
      noted. The DIL data included initial base curve, power, and the number of changes
      made in parameters during the follow-up. The outcome data included visual acuity
      and the duration of follow-up and lens wear. Complications and complaints were
      also noted. RESULTS: Twenty-seven eyes of 22 patients were reviewed. Fourteen
      eyes had PMD; seven had keratoconus; and six eyes had undergone PK. The mean age
      of patients was 52.7 +/- 13.1 years. The mean follow-up was 8.9 +/- 7.4 months.
      Nine (33.3%) eyes achieved 20/20 visual acuity; 13 (48.1%) eyes achieved 20/25 to
      20/40; and five (18.5%) eyes achieved 20/50 to 20/70. Fifteen (55.6%) eyes
      achieved visual improvement (two lines or more). The mean number of refits was
      1.1 +/- 0.9. No infection or neovascularization was noted; a corneal abrasion
      occurred in one eye. Good wearing time was achieved in 18 (66.7%) eyes of 13
      patients, who were still wearing DILs at the last follow-up. CONCLUSIONS: DILs
      may be a good alternative in selected patients with flat central and superior
      corneas and inferior peripheral steepening.

PMID- 16415687
TI  - Pseudomonas aeruginosa-induced inflammation in the rat extended-wear contact lens
      model.
AB  - PURPOSE: To examine the early host response to Pseudomonas aeruginosa challenge
      in the extended contact lens-wearing rat model. METHODS: Lewis rats were fitted
      with extended-wear lotrafilcon A hydrogel lenses in the left eye, and the right
      eye served as the control. Bacterial challenge was initiated in the experimental
      eye by fitting a bacteria-soaked contact lens and by topical delivery of the
      bacteria. On first detection of corneal opacity, slitlamp examination,
      histopathologic examination, viable bacteria counts, enzyme-linked immunosorbent
      assay, myeloperoxidase, Langerhans cell detection, and multiprobe ribonuclease
      protection assays were used to evaluate the early corneal response. RESULTS:
      Analysis of bacterially challenged contact lens-wearing versus control rats
      showed Langerhans cells and polymorphonuclear neutrophils only in the
      experimentally challenged cornea. In addition, in the experimentally challenged
      cornea, ribonuclease protection and enzyme-linked immunosorbent analyses showed
      an upregulation of proinflammatory cytokines, including interleukins 1beta and 6,
      suggesting that with contact lens wear, these cytokines contribute to the early
      corneal response and, potentially, disease. CONCLUSIONS: The contact lens-wearing
      rat model allows a unique analysis of the early effects of bacterial challenge in
      extended-wear contact lenses in the absence of corneal scarring, used in most
      rodent models. The rat model should be valuable to delineate further the effects
      of contact lens wear, including the testing of additional contact lens-related
      complications.

PMID- 16415692
TI  - A case of acanthamoeba keratitis as a result of a cosmetic contact lens.
AB  - PURPOSE: To describe a case of Acanthamoeba keratitis that resulted from a
      cosmetic contact lens purchased from an unlicensed vendor. METHODS: Case report.
      RESULTS: A 26-year-old man developed Acanthamoeba keratitis from a cosmetic
      contact lens and ultimately required a penetrating keratoplasty. The patient then
      developed angle-closure glaucoma and required a trabeculectomy. CONCLUSIONS: This
      case shows the potential ocular danger involved with unauthorized sale of
      cosmetic contact lenses.

PMID- 16415693
TI  - Overnight orthokeratology experience with XO material.
AB  - PURPOSE: To evaluate long-term safety and effectiveness of overnight
      orthokeratology in a large sample of myopes by using three different lens designs
      and the highly gas-permeable Boston XO material (Bausch & Lomb, Rochester, NY).
      METHODS: A total of three hundred forty-two subjects, 99 of whom were juveniles,
      were enrolled in the investigation at 26 clinical centers in the United States
      and Canada. Three different lens designs in Boston XO material were used.
      Subjects were limited to a measured visual need for correction of myopia less
      than or equal to 4.00 diopters and astigmatism less than or equal to 1.50
      diopters with best-corrected Snellen visual acuity of 20/40 or better. Refractive
      error and unaided visual acuity were used to determine the effectiveness of the
      procedure at short-term (1 month) and long-term (12 months). The safety of the
      procedure was determined by the symptoms reported, and slitlamp findings
      suggested physiologic rejection of the procedure. RESULTS: One hundred thirty
      three adults and 68 juveniles completed the 12-month study. More than 60% of the
      subjects reached 20/20 vision or better at the end of 1 month of overnight lens
      wear, and this number remained stable during the next 11 months. A reduction in
      myopia of 70% and of more than 90% was measured at the 1- and 12-month visits,
      respectively. Safety data indicate a decrease in symptoms and in general a
      decrease in positive slitlamp findings with time. CONCLUSIONS: The procedure with
      all three lenses in Boston XO material is effective. However, the safe use of
      orthokeratology lenses is predicated on the emphasis of clear patient direction
      on how to wear and take care of the lenses followed by regular examinations by an
      eye care practitioner.

PMID- 16415695
TI  - Biomechanically coupled curvature transfer in normal and keratoconus corneal
      collagen.
AB  - PURPOSE: To examine the hypotheses that a "pushed" biomechanically coupled
      intrafibrillar transfer of curvature may be involved in corneal warpage (pseudo
      cone) development, which is observed with superior cornea-bearing rigid contact
      lens fittings, and that a "pulled" biomechanically coupled intrafibrillar
      transfer of curvature may be involved in keratoconus cone development. METHODS:
      The mechanical properties of corneal stromal fibrils have been reviewed to
      examine the histologic basis for fibril inextensibility and the associated
      potential for them to demonstrate biomechanical coupling. DISCUSSION: The
      hypothesis that apical clearance rigid contact lenses may promote pushed
      biomechanical responses that aid cone development in some normal or keratoconic
      corneas is examined. CONCLUSIONS: Stromal fibrils that run limbus to limbus and
      have circumferential stability at the limbus, appear to be relatively
      inextensible: a finding that is consistent with the need for stable refraction.
      The property of inextensibility could also support intrafibrillar biomechanically
      coupled curvature transfer. For example, in some normal corneas, definite apical
      clearance fittings may be associated with biomechanically coupled push forces
      generated by midperipheral bearing that squeeze the central cornea to greater
      curvature. A disease-related biomechanically coupled pull mechanism for cone
      formation may be accelerated by an apical clearance fitting push mechanism, with
      additional synergy generated by subatmospheric pressure in the postlens tear
      pool. These fitting-related mechanisms appear likely to increase with the degree
      of apical clearance. Cone formation in keratoconus and models of external forces
      acting on the cornea (tonometry and contact lens-related) are mathematically
      analyzed for an idealized one-dimensional elastic model of a corneal stromal
      fibril. The classic theory of "elastic rods" is adopted, and despite the
      nonlinear nature of the differential equations involved, a method of dealing with
      biomechanically coupled curvature transfer in an "exact" manner is described and
      used to model the related clinical phenomena.

PMID- 16415694
TI  - A comparison of gatifloxacin to ciprofloxacin in the prophylaxis of Streptococcus
      pneumoniae in rabbits in a LASIK model.
AB  - PURPOSE: To investigate the efficacy of the fourth-generation fluoroquinolone,
      gatifloxacin 0.3%, compared to ciprofloxacin 0.3%, in preventing Streptococcus
      pneumoniae keratitis in a rabbit laser in situ keratomileusis (LASIK) model.
      METHODS: Twelve albino rabbits had bilateral lamellar flaps created. Group A
      (eight eyes) was given gatifloxacin 0.3%; group B (eight eyes) was given
      ciprofloxacin 0.3%; and group C (eight eyes) served as the controls. Groups A and
      B received one drop of antibiotic 20 minutes before the creation of the lamellar
      flap, at the conclusion of flap formation, and four times per day for 3 days. All
      corneas were inoculated with 0.1 mL of 4 x 10 organisms/mL of S. pneumoniae
      immediately after flap formation. On day 3, all corneas were examined and
      cultured. RESULTS: Group A (gatifloxacin) had no infiltrates and three areas of 1
      mm central corneal haze. On day 3, one of eight corneas had a positive culture.
      Group B (ciprofloxacin) had seven infiltrates, including one perforation, and six
      of eight corneas had positive cultures. Group C (control) had eight corneal
      infiltrates, and all eight corneas had positive cultures. The data show a
      statistically significant difference between gatifloxacin and ciprofloxacin and
      gatifloxacin and control for mean infiltrate size and mean culture scores.
      CONCLUSIONS: The fourth-generation fluoroquinolone, topical gatifloxacin 0.3%, is
      superior to topical ciprofloxacin 0.3% for prophylaxis against a clinical isolate
      of S. pneumoniae in a rabbit LASIK model.

PMID- 16415696
TI  - Pharmacologic management of dental anxiety: conscious versus unconscious
      sedation.

PMID- 16415697
TI  - Pharmacokinetics and clinical effects of multidose sublingual triazolam in
      healthy volunteers.
AB  - Triazolam is increasing in popularity as a premedication prescribed by dentists
      to help their fearful and anxious patients tolerate the potentially aversive
      nature of some dental procedures. Recent anecdotal reports suggest that
      incremental sublingual dosing of triazolam may be an effective technique for
      producing conscious sedation in the dental setting. Although promising, no
      laboratory or clinical data have been available to evaluate the efficacy or
      safety of this approach. This study was designed to determine the
      pharmacokinetics and sedative effects of incremental sublingual dosing of
      triazolam (total, 1.0 mg) in healthy adults. Ten healthy adult volunteers
      received sublingual triazolam (0.25 mg) followed by additional doses after 60
      (0.50 mg) and 90 (0.25 mg) minutes. Plasma triazolam concentrations, clinical
      effects (Observer's Assessment of Alertness/Sedation score), and processed
      electroencephalogram (bispectral index score) were measured intermittently for 3
      hours. Plasma triazolam concentrations (mean +/- SD, 5.1 +/- 1.1 ng/mL) and drug
      effects (Observer's Assessment of Alertness/Sedation score, 2 +/- 1; and the
      bispectral index score, 62 +/- 16) were greatest in all subjects at the end of
      the 3-hour evaluation period. Eight of the subjects had Observer's Assessment of
      Alertness/Sedation scores consistent with the definition of deep sedation or
      general anesthesia (Observer's Assessment of Alertness/Sedation score, <3) at
      some of the later time points in the 180 minutes of data collection. In
      comparison, 4 of the subjects had bispectral index scores less than 60 during
      these later time points of data collection. Given the considerable intersubject
      variability in triazolam concentrations and effects, additional research is
      needed to assess this multidosing strategy before it can be endorsed as a useful
      and safe sedation technique for managing fearful and anxious patients in dental
      practice.

PMID- 16415698
TI  - The efficacy of olanzapine for decreasing cue-elicited craving in individuals
      with schizophrenia and cocaine dependence: a preliminary report.
AB  - OBJECTIVE: Although a growing body of research suggests that atypical neuroleptic
      medications are efficacious in the treatment of cocaine addiction among
      individuals with schizophrenia, more rigorously controlled trials are needed. To
      extend this research, we performed a 6-week double-blind study comparing
      olanzapine to haloperidol with the primary objective of reducing cue-elicited
      cocaine craving and the secondary aims of decreasing substance use, improving
      psychiatric symptoms, and determining an effect size for future studies. METHODS:
      Thirty-one subjects with cocaine dependence and schizophrenia were randomized to
      olanzapine or haloperidol, underwent a cue-exposure procedure, and completed
      psychiatric and substance abuse ratings. RESULTS: Individuals in the olanzapine
      group who completed the study had a significant reduction on the energy subscale
      of the Voris Cocaine Craving Scale at study completion compared with individuals
      in the haloperidol group. The olanzapine-treated group also had lower, but not
      statistically significant, PANSS General Psychopathology Subscale scores and
      fewer positive urine toxicology screens compared with those in the haloperidol
      group. CONCLUSION: This small, but rigorously controlled, pilot trial provides
      additional evidence for the use of atypical antipsychotics for the treatment of
      individuals with co-occurring schizophrenia and cocaine dependence. Reductions in
      craving were associated with medium to large effect sizes.

PMID- 16415699
TI  - Sertraline treatment of co-occurring alcohol dependence and major depression.
AB  - BACKGROUND: Major depressive disorder occurs commonly in association with alcohol
      dependence, both in clinical samples and in the community. Efforts to treat major
      depressive disorder in alcoholics with antidepressants have yielded mixed
      results. This multicenter, double-blind, placebo-controlled trial of sertraline
      was designed to address many of the potential methodological shortcomings of
      studies of co-occurring disorders. METHOD: Following a 1-week, single-blind,
      placebo lead-in period, 328 patients with co-occurring major depressive disorder
      and alcohol dependence were randomly assigned to receive 10 weeks of treatment
      with sertraline (at a maximum dose of 200 mg/d) or matching placebo.
      Randomization was stratified, based on whether initially elevated scores on the
      17-item Hamilton Depression Rating Scale declined with cessation of heavy
      drinking, resulting in a sample of 189 patients with Hamilton Depression Rating
      Scale scores > or =17 (group A) and 139 patients with Hamilton Depression Rating
      Scale scores < or =16 (group B). RESULTS: Both depressive symptoms and alcohol
      consumption decreased substantially over time in both groups. There were no
      reliable medication group differences on depressive symptoms or drinking behavior
      in either group A or B patients. CONCLUSION: Despite careful attention to
      methodological considerations, this study does not provide consistent support for
      the use of sertraline to treat co-occurring major depressive disorder and alcohol
      dependence. The high rate of response among placebo-treated patients may help to
      explain these findings. Further research is needed to identify efficacious
      treatments for patients with these commonly co-occurring disorders.

PMID- 16415700
TI  - Bupropion improves sexual functioning in depressed minority women: an open-label
      switch study.
AB  - Minority women often have a unique set of beliefs and expectations about medical
      treatment. At this time, there is a dearth of research looking at how depressed
      minority women respond to pharmacological interventions for the sexual
      concomitants of depression. This was the first study to examine the impact of a
      medication switch, from a selective serotonin reuptake inhibitor to bupropion SR,
      on the sexual functioning of depressed minority women. Eighteen minority women (5
      Hispanic, 10 African American, 2 Asian American, and 1 Native American), who were
      experiencing poor tolerability and/or lack of efficacy on an adequate trial of a
      selective serotonin reuptake inhibitor for depression, along with low sexual
      desire, were enrolled in this prospective open-label study. The selective
      serotonin reuptake inhibitor and bupropion SR were cross-tapered with a target
      dose of 150 to 300 mg of bupropion SR. The patients were followed for 10 weeks,
      and measures of sexual functioning and depression (Hamilton Rating Scale for
      Depression) were administered in an academic medical setting. Data were collected
      from July 2003 to December 2004. In the group as a whole, there were significant
      improvements in desire (F1,17 = 34.86, P < 0.001), arousal (F1,17 = 25.99, P <
      0.001), and orgasm (F1,17 = 20.16, P < 0.001), on the Changes in Sexual
      Functioning Questionnaire. African-American women demonstrated the greatest
      improvement in depression (F1,16 = 9.55, P = 0.006), desire (F1,16 = 8.62, P =
      0.01), and arousal (F1,16 = 8.83, P = 0.009) after the medication switch.
      Overall, this intervention appeared to be an effective treatment of low sexual
      desire in a diverse group of depressed minority women. The majority of women
      successfully completed the trial and planned to continue using bupropion SR after
      their participation in the study.

PMID- 16415702
TI  - Safety and efficacy of tramadol in the treatment of premature ejaculation: a
      double-blind, placebo-controlled, fixed-dose, randomized study.
AB  - PURPOSE: To evaluate the efficacy and safety of a new serotonergic centrally
      acting drug tramadol in delaying ejaculation in patients with premature
      ejaculation. MATERIALS AND METHODS: Sixty-four potent men with premature
      ejaculation were randomly assigned to receive 50 mg tramadol (group 1, n = 32) or
      placebo (group 2, n = 32) approximately 2 hours before planned sexual activity,
      for 8 weeks. Pretreatment evaluation included history and physical examination,
      intravaginal ejaculatory latency time, International Index of Erectile Function,
      and Meares-Stamey test. The efficacy of 2 treatments was assessed using responses
      to International Index of Erectile Function, intravaginal ejaculatory latency
      time evaluation, and several general assessment questions. RESULTS: Fifty-seven
      (89%) completed the whole treatment schedule. The mean intravaginal ejaculatory
      latency time after tramadol and placebo increased from 19 and 21 seconds to
      approximately 243 and 34 seconds, respectively (P < 0.001). The mean weekly
      intercourse episodes increased from pretreatment values of 1.07 and 1.1 to 2.3
      and 1.3, for tramadol and placebo, respectively (P < 0.05). Baseline mean
      intercourse satisfaction domain values of International Index of Erectile
      Function 10 and 11 reached to 14 and 10 at 8-week treatment in groups 1 and 2,
      respectively (P < 0.05). There was no withdrawal caused by adverse effects with
      tramadol or placebo, but more adverse events were associated with tramadol
      treatment (P < 0.05). CONCLUSIONS: Tramadol seems to provide significantly better
      results in terms of intravaginal ejaculatory latency time and intercourse
      satisfaction versus placebo. Further studies are required to draw final
      conclusions on the efficacy of this drug in premature ejaculation.

PMID- 16415703
TI  - The effects of sertraline on severe tinnitus suffering--a randomized, double
      blind, placebo-controlled study.
AB  - OBJECTIVE: The relationship between tinnitus and anxiety and depressive disorders
      has been frequently alluded to, but there are few studies on antidepressants in
      the treatment of tinnitus, and the efficacy of sertraline on severe refractory
      tinnitus has not been reported. METHOD: Consecutive tinnitus patients (n = 76)
      considered to be at high risk for severe and disabling tinnitus according to a
      recently developed screening procedure were randomly assigned to 16 weeks of
      double-blind treatment with placebo (n = 38) or sertraline (n = 38) at a fixed
      dose (25 mg/d on the first week and 50 mg/d on the following 15 weeks). Between
      group comparisons of Tinnitus Severity Questionnaire scores over 16 weeks were
      made as the primary outcome measure. Secondary outcomes of tinnitus loudness and
      tinnitus annoyance were also measured using a visual analogue scale. Severity of
      depressive and anxiety symptoms was evaluated using the Hamilton rating scales
      (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, interview
      based ratings) and the Comprehensive Psychopathological Rating Scale (self
      ratings). RESULTS: The intention-to-treat analysis showed sertraline to be more
      effective than placebo (P = 0.024) in decreasing reported tinnitus severity
      according to the Tinnitus Severity Questionnaire at 16 weeks' follow-up. There
      was also more improvement (P = 0.014) in perceived tinnitus loudness. There were
      significant correlations between reduction of tinnitus according to the Tinnitus
      Severity Questionnaire over 16 weeks and improvements in depressive (r = 0.42
      0.46) and anxiety symptoms (r = 0.34-0.42). Sertraline was well tolerated after a
      somewhat high (17%) dropout rate within the first 2 weeks. CONCLUSIONS:
      Sertraline is more effective than placebo in the treatment of severe refractory
      tinnitus.

PMID- 16415704
TI  - Is quality of life among minimally symptomatic patients with schizophrenia better
      following withdrawal or continuation of antipsychotic treatment?
AB  - This secondary report from our 52-week, double-blind, relapse prevention trial
      tested whether stable patients with schizophrenia who were taken off active drug
      treatment would experience greater improvements in long-term quality of life than
      those who were continued on antipsychotic treatment. On average, Heinrichs
      Carpenter Quality-of-Life Scale total scores improved by 4.3 +/- 10.6 points
      during treatment with olanzapine (10-20 mg/d; n = 212), but decreased by 7.1 +/-
      14.6 points during treatment with placebo (n = 92; P < 0.001). Mean Quality-of
      Life Scale total scores worsened in both treatment groups for the relapsing
      patient subgroup, whereas for nonrelapsing patients, those treated with
      olanzapine had significantly improved mean Quality-of-Life Scale total scores
      compared with those given placebo. For a subset of nonrelapsing patients who were
      considered "nonexacerbating" on the basis of minimal non-clinically relevant
      increases in psychopathology, Quality-of-Life Scale total mean change was no
      better (P = 0.066) for those given placebo (2.7 +/- 11.0; n = 40) than those
      treated with olanzapine (5.7 +/- 8.9; n = 174). Path analysis indicated a direct
      effect of treatment (approximately 29%) on quality of life that was not accounted
      for by differential changes in psychopathology. In conclusion, stable patients
      with schizophrenia who were taken off active drug treatment experienced no
      greater improvements in long-term quality of life than those who were continued
      on antipsychotic treatment, even in the absence of psychotic symptoms.

PMID- 16415706
TI  - Reducing the dose of antipsychotic agents ameliorates visual hypersensitivity
      attack: an ideal treatment option in terms of the adverse effect.
AB  - There are sporadic reports of antipsychotic-induced visual hypersensitivity
      attack (VHA). VHA is characterized by hypersensitivity of perception mainly in
      the visual modality and sometimes accompanied by an oculogyric crisis. However,
      some researchers regard VHA as a schizophrenia symptom. To determine whether VHA
      is an adverse effect of antipsychotic agents, we examined the effect of dose
      reduction on VHA. This was an open-label 36-week study. We randomized 34 patients
      with VHA to a reduced-dose group and a fixed-dose group. Primary outcome measures
      were the frequency and duration of VHA, assessed with patients' self-reports, and
      the Clinical Global Impressions (CGI). Assessment also included the Drug-induced
      Extrapyramidal Symptoms Scale for extrapyramidal symptoms, the Positive and
      Negative Syndrome Scale (PANSS) for schizophrenia, and the CGI for other
      diagnoses. Data were collected from August 2000 to April 2005 at 4 psychiatric
      hospitals in Tokyo.VHA diminished in 16 patients (94.1%) in the reduced-dose
      group in the CGI score, the frequency (number of episodes per week), and the
      duration of the episodes (from 4.06 to 1.77, P < 0.001; from 2.59 to 0.82, P =
      0.001; and from 1.92 to 0.66 hours, P = 0.007, respectively), but there were no
      changes in the fixed-dose group. There were no changes in the underlying illness
      as measured by the PANSS in both groups. Reducing the dose of antipsychotic
      agents ameliorates VHA and represents the ideal treatment option for patients
      with VHA.

PMID- 16415705
TI  - Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed
      dose, open-label trial.
AB  - The purpose of our study was to evaluate the efficacy and tolerability of low
      dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)
      resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open
      label study, 31 adult outpatients with treatment-resistant PD who had previously
      failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5
      mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and
      Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire
      (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale
      for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the
      Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed
      the trial period with a dropout rate of 16.1%. At week 12, 21 patients were
      responders (81.8%), and an overall improvement on all rating scales was observed
      in all patients both with or without agoraphobia. Fifteen patients (57.7%)
      achieved remission. Olanzapine was well tolerated and the most frequent adverse
      effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal
      symptoms were reported. Olanzapine appears to be effective as augmentation
      strategy in the treatment of SSRI-resistant PD, but study limitations must be
      considered and placebo-controlled studies are needed.

PMID- 16415707
TI  - A meta-analysis of early sustained response rates between antidepressants and
      placebo for the treatment of major depressive disorder.
AB  - CONTEXT: Pattern analysis suggests that "true" drug response is characterized by
      clinical improvement that is not subsequently followed by a worsening of symptoms
      (sustained clinical response). To date, several reports demonstrate that early
      response rates are equivalent between antidepressant-treated and placebo-treated
      groups of patients with major depressive disorder, suggesting that patients who
      demonstrate significant and sustained symptom improvement during the first 2
      weeks of treatment are not responding to the antidepressant itself, but to
      nonspecific, placebo-like factors. OBJECTIVE: To compare early sustained response
      rates between antidepressant- and placebo-treated adults with major depressive
      disorder. DATA SOURCES: Medline/Pubmed were searched. No year of publication
      limits were used. STUDY SELECTION: Randomized, double-blind, placebo-controlled
      antidepressant trials or pooled reports/meta-analyses of such trials reporting
      early sustained response rates for major depressive disorder. The decision to
      include studies in the meta-analysis was performed by 2 reviewers. DATA
      EXTRACTION: Data were extracted with the use of a precoded form. DATA SYNTHESIS:
      Analyses were performed on the proportion of patients who achieved a sustained
      response the first 2 weeks of treatment, as well as the first week of treatment.
      A random-effects model with fixed drug effects was used to combine the studies
      and make comparisons of sustained early response rates between antidepressant-
      and placebo-treated groups. Data from 8 reports involving a total of 7121 major
      depressive disorder patients (4076 randomized to treatment with an antidepressant
      and 3045 randomized to placebo) were analyzed. Antidepressant-treated patients
      were more likely to demonstrate sustained clinical response by 2 weeks (odds
      ratio 2.06, 95% CI: 1.52-2.8) or 1 week of treatment (odds ratio 1.50, 95% CI:
      1.08-2.08) than placebo-treated patients. CONCLUSIONS: The results of the present
      analysis suggest that "true" drug response can occur the first 2 week as well as
      the first week of treatment of major depressive disorder with conventional
      antidepressants.

PMID- 16415708
TI  - Topiramate treatment for women with borderline personality disorder: a double
      blind, placebo-controlled study.
AB  - Borderline personality disorder is a common and severe psychiatric illness. The
      goal of this study was to determine whether topiramate can influence patients'
      borderline psychopathology, health-related quality of life, and interpersonal
      problems. Women meeting the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition Structured Clinical Interview II criteria for
      borderline personality disorder were randomly assigned in a 1:1 ratio to
      topiramate titrated from 25 to 200 mg/d (n = 28) or placebo (n = 28) for 10
      weeks. Primary outcome measures were changes on the Symptom-Checklist, on the SF
      36 Health Survey, and on the Inventory of Interpersonal Problems. Body weight and
      additional side effects were assessed weekly. According to the intent-to-treat
      principle, significant changes (all P < 0.001) on the somatization, interpersonal
      sensitivity, anxiety, hostility, phobic anxiety, and Global Severity Index scales
      of the Symptom Checklist were observed in the topiramate-treated subjects after
      10 weeks (no significant changes on the obsessive-compulsive, depression,
      paranoid ideation, and psychoticism scales). In the SF-36 Health Survey,
      significant differences were observed on all 8 scales (all P < 0.01 or P <
      0.001). In the Inventory of Interpersonal Problems, significant differences (all
      P < 0.001) were found in the scales for overly autocratic, overly competitive,
      overly introverted, and overly expressive (no significant differences in the
      scales for overly cold, overly subassertive/subservient, overly
      exploitable/compliant, and overly nurturant/friendly). Weight loss was
      additionally observed (p < 0.001). Topiramate appears to be a safe and effective
      agent in the treatment in women with borderline personality disorder. Additional
      weight loss can be expected.

PMID- 16415709
TI  - New possibilities of treatment for panic attacks in elderly patients:
      escitalopram versus citalopram.
AB  - PURPOSE: Panic attacks may represent additional therapeutic problems in the
      elderly. The utility of citalopram in panic attacks has been widely investigated.
      Here, we compare the efficacy and safety of citalopram, with its S-enantiomer
      escitalopram at half dosage as to citalopram, in elderly patients who have panic
      attacks. METHODS: This was an open community-based study. Forty patients who have
      panic attacks, according to Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria, were enrolled. Fifty percent of the patients
      were assigned for 8 weeks' treatment with escitalopram, and the remaining 50%
      were assigned to treatment with citalopram. The primary outcome measure was the
      weekly rate of panic attacks. The secondary outcome measures were the Hamilton
      scale for anxiety and depression and the Cooper Disability Scale. Analysis of
      variance by repeated measures was applied to calculate differences between
      groups. RESULTS: A similar decrease in weekly rate of panic attacks, in the
      scores of Hamilton Scale for anxiety and depression and in the Cooper Disability
      Scale scores, was observed in both groups after 8 weeks, but a significant
      variation of outcome measures from baseline was observed already after 2 weeks in
      the escitalopram group (P < 0.001) and only after 4 weeks in the citalopram group
      (P < 0.01). CONCLUSIONS: Escitalopram could be considered among the drugs of
      first choice in elderly patients with panic attacks because of its good efficacy
      and safety and for the advantage of reducing the total dose and of a more rapid
      onset of action as compared with citalopram, although further studies are needed
      to confirm these results.

PMID- 16415710
TI  - Rating the raters: assessing the quality of Hamilton rating scale for depression
      clinical interviews in two industry-sponsored clinical drug trials.
AB  - OBJECTIVE: The quality of clinical interviews conducted in industry-sponsored
      clinical drug trials is an important but frequently overlooked variable that may
      influence the outcome of a study. We evaluated the quality of Hamilton Rating
      Scale for Depression (HAM-D) clinical interviews performed at baseline in 2
      similar multicenter, randomized, placebo-controlled depression trials sponsored
      by 2 pharmaceutical companies. METHODS: A total of 104 audiotaped HAM-D clinical
      interviews were evaluated by a blinded expert reviewer for interview quality
      using the Rater Applied Performance Scale (RAPS). The RAPS assesses adherence to
      a structured interview guide, clarification of and follow-up to patient
      responses, neutrality, rapport, and adequacy of information obtained. RESULTS:
      HAM-D interviews were brief and cursory and the quality of interviews was below
      what would be expected in a clinical drug trial. Thirty-nine percent of the
      interviews were conducted in 10 minutes or less, and most interviews were rated
      fair or unsatisfactory on most RAPS dimensions. CONCLUSIONS: Results from our
      small sample illustrate that the clinical interview skills of raters who
      administered the HAM-D were below what many would consider acceptable. Evaluation
      and training of clinical interview skills should be considered as part of a rater
      training program.

PMID- 16415712
TI  - Pulse-loaded intravenous clomipramine in treatment-resistant obsessive-compulsive
      disorder.
AB  - INTRODUCTION: Small studies have suggested that intravenous clomipramine (CMI)
      may be more effective and induce faster improvement in obsessive-compulsive
      disorder than do orally administered serotonin reuptake inhibitors. OBJECTIVE: To
      test these hypotheses, we conducted a randomized, double-blind, double-dummy
      study of pulse-loaded intravenous versus oral CMI, followed by open-label oral
      CMI for 12 weeks. METHODS: We enrolled a volunteer and referred group of 34
      adults with a primary diagnosis of Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition obsessive-compulsive disorder of > or =1-year duration
      and Yale-Brown Obsessive Scale score of > or =20. Eligible subjects had failed >
      or =2 adequate serotonin reuptake inhibitor trials. Subjects received pulse
      loaded CMI 150 mg by vein or by mouth on day 1 and 200 mg on day 2. Oral CMI
      began on day 6 at 200 mg/d and was increased by 25 mg every 4 days to 250 mg/d,
      as tolerated, for 12 weeks. RESULTS: Adverse events led to one withdrawal during
      oral pulse loading and 5 during open-label oral treatment. Intravenous pulse
      loading did not induce a more rapid or greater Yale-Brown Obsessive Scale score
      decrease than oral pulse loading at day 6 or by week 12. Day 6 and week 12
      improvement were unrelated to plasma drug or metabolite concentrations. Pulse
      loading itself seemed to induce more rapid and greater improvement than expected
      in treatment-resistant obsessive-compulsive disorder. CONCLUSIONS: Further
      investigation of oral pulse-loading regimens in treatment-resistant obsessive
      compulsive disorder is warranted.

PMID- 16415711
TI  - Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a
      double-blind, randomized multicenter trial comparing the onset of antidepressant
      response in patients with major depressive disorder.
AB  - This randomized, multicenter, double-blind study was designed to compare
      specifically the onset of antidepressant action of mirtazapine orally
      disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation
      in outpatients with major depression. Both treatments were administered in a
      rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD;
      venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary
      efficacy parameter [the average of the change in HAM-D (17-item) total score on
      days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine
      XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items
      resulted in significant reductions in favor of mirtazapine ODT on days 8 (P =
      0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or
      =50% from baseline) was higher in the mirtazapine ODT group on all assessment
      days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P =
      0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D
      total score of < or =7) up to day 29, and the difference was statistically
      significant on day 15 (P = 0.016). Significant differences in favor of
      mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P =
      0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11
      (P = 0.033). Both treatments were well tolerated. These results indicate that
      mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR
      in patients with major depressive disorder, and that this effect is independent
      of its sleep-improving properties.

PMID- 16415713
TI  - Treatment of chronic posttraumatic stress disorder in combat veterans with
      citalopram: an open trial.
AB  - Posttraumatic stress disorder (PTSD) is a serious mental illness which exhibits
      significant impairment of psychosocial and occupational function. At present,
      serotonin reuptake inhibitors (SRIs) show therapeutic promise for the treatment
      of PTSD. However, results in the veteran population have been less robust or
      often negative. In this study, a relatively new and the most selective SRI,
      citalopram, was evaluated for the treatment of PTSD. Veterans with chronic PTSD
      (N = 18) were enrolled in an 8-week open trial of citalopram after providing
      written informed consent. The primary outcome measures were the Clinician
      Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Anxiety (HAM-A),
      and the Clinical Global Impression Scale (CGI). Seventeen patients completed at
      least 4 weeks of the 8-week trial. During treatment, there was a moderate
      response with 42% of patients demonstrating a > or =30% reduction in total CAPS
      score at week 8. Comparable results were demonstrated in the Hamilton Depression
      Rating Scale (HAM-D), HAM-A, Global Assessment of Function (GAF), and CGI rating
      scales. In a follow-up analysis, a treatment effect was shown for CAPS B at week
      4, but was not sustained at week 8. Overall, citalopram was generally well
      tolerated with reported adverse events being benign in nature. These pilot
      results demonstrate a moderate effect of citalopram in the treatment of combat
      induced PTSD. However, the sample size was small and patient population is
      limited to veterans with combat-induced PTSD. Further study in a larger and more
      diverse patient sample is warranted prior to final conclusions on efficacy of
      citalopram for the treatment of PTSD.

PMID- 16415714
TI  - Clozapine-associated pseudomembranous colitis: a case report and review of the
      literature.

PMID- 16415715
TI  - An open trial of olanzapine in children and adolescents with Asperger Disorder.

PMID- 16415716
TI  - Diabetic ketoacidosis and severe dyslipidemia in an adult psychotic man with
      olanzapine treatment.

PMID- 16415717
TI  - Neuroleptic malignant syndrome and aripiprazole in an antipsychotic-naive
      patient.

PMID- 16415718
TI  - An open-label trial of adjunctive oxcarbazepine for bipolar disorder.

PMID- 16415719
TI  - Venlafaxine and the rapid development of anasarca.

PMID- 16415720
TI  - Response to SSRI-induced enuresis: a case report.

PMID- 16415721
TI  - Treatment of psychogenic polydipsia with pindolol.

PMID- 16415722
TI  - Priapism and quetiapine in an HIV-positive male.

PMID- 16415723
TI  - Aripiprazole as a dopamine partial agonist: positive and negative effects.

PMID- 16415724
TI  - The interaction between superoxide dismutase and prolactin is involved in
      response to haloperidol and risperidone treatment in schizophrenia: a double
      blind and randomized study.

PMID- 16415725
TI  - Pharmacokinetic profile of an oral loading dose of divalproex sodium during acute
      alcohol withdrawal.

PMID- 16415726
TI  - Amputation and the diabetic foot: learning from a case study.
AB  - Diabetic foot disease causes more amputations than any other lower limb disease.
      Management of the diabetic foot requires a thorough knowledge of the risk factors
      for ulceration and amputation, the most common of which are neuropathy, ischaemia
      and infection. Amputations are not inevitable, however; early detection and
      appropriate treatment of ulcers can prevent up to 85% of amputations. This has
      been demonstrated in the formation of multidisciplinary diabetic foot clinics,
      which have been shown to reduce the number of amputations across the world.
      Adherence to a systematic regime of organization, education, screening and
      intervention can improve communication between patients, GPs, community nursing
      and diabetes sub-specialists to facilitate appropriate treatment and prevention
      of complications. The case discussed here demonstrates how inadequate and
      disjointed management through lack of communication, education and knowledge of
      diabetic foot disease can lead to complications requiring amputation and
      debridement.

PMID- 16415727
TI  - A static-led approach to effective equipment management.
AB  - Ashton, Leigh and Wigan Primary Care Trust has a static-led approach to the
      provision of pressure-relieving equipment in the community. This means that
      product selection must result from an individualized clinical assessment of the
      patients needs and not reliant on a blanket approach. The limitations of dynamics
      should be considered and the delivery of essential nursing care should be deemed
      paramount, rather than products. The emphasis within the PCT is on holistic
      assessment and informed clinical decision-making, combined with education of
      patients and carers in use of equipment. This article sets out the rationale for
      a static-led approach, and reports the results of a survey of district nurses
      which looked at their practice in this area.

PMID- 16415728
TI  - Politics and the future of wound care.

PMID- 16415730
TI  - A bumper gift for community nursing.

PMID- 16415732
TI  - Removing indwelling catheters: trial without catheter in the community.
AB  - Indwelling urinary catheters are inserted to drain the bladder for a variety of
      reasons, but are an intervention of last resort. Unless contraindicated, patients
      with an indwelling catheter should therefore have at least one trial without
      catheter to assess if they can pass urine without having a catheter in situ. The
      commonest method in undertaking trial without catheter is to remove a indwelling
      urethral catheter and monitor urinary output over a period of time. Another
      method is when the catheter is not removed in patients who have a suprapubic
      catheter. Instead the catheter is clamped, and urethral urine output monitored.
      This is followed by immediately measuring any residue of urine drained via the
      supra-pubic catheter. This article looks at undertaking a 'trial without
      catheter' using both methods and examines the arguments concerning when to remove
      catheters, midnight or early in the morning.

PMID- 16415731
TI  - Long-term conditions: making sense of the current policy agenda.
AB  - This article is first of a series focusing on long-term conditions and aims to
      guide district nurses through the whole raft of policies that are currently
      emerging from the Department of Health for England and Wales. The article
      provides an overview of current policy by taking the reader through the
      initiatives, starting with population-wide prevention and concluding with
      policies focusing on clients with complex needs. The main triggers for government
      health strategies and the influence of models from the United States are
      discussed. The national service framework for long term conditions is explained
      and used as an example of the current emphasis on generic, rather than condition
      specific, initiatives. The article concludes by drawing the initiatives together
      within the most recent model to come out of the Department of Health--the NHS and
      Social Care Model.

PMID- 16415729
TI  - Improving pressure ulcer prevention in a nursing home: action research.
AB  - A study conducted in Sunderland investigated how staff in a private sector care
      home manage pressure ulcer prevention and what staff perceive to be the reasons
      why residents in their care develop pressure ulcers. It also identified how using
      a collaborative action research study design (utilizing an action research cycle
      with collaborative focus groups) can bring about an improvement in practice, by
      allowing the staff to reflect on and analyse the way they work and develop and
      implement strategies to provide solutions to the problems they identify.

PMID- 16415733
TI  - The progress of family health nursing in remote and rural Scotland.
AB  - Since 2001 the World Health Organization Europe's family health nurse (FHN) role
      has been developing in remote and rural areas of Scotland. In 2003, an
      independent evaluation identified a need for facilitation of the FHN role and
      family-health orientated approaches with local primary health care teams. The
      Scottish Executive Health Department appointed three part-time, regionally-based
      family health practice development facilitators (FHPDFs) in December 2003 to work
      over an 18-month period. This article presents findings from a small study which
      sought these FHPDFs' judgements on individual FHN autonomy and supportive
      colleague action at 24 sites where FHNs were practising. These judgements reveal
      a picture of mixed progress that is consistent with findings from other related
      research. This collective overview is presented in the form of a new typology and
      the resultant implications for future development of family health nursing are
      discussed.

PMID- 16415734
TI  - Managing student transitions into primary care.
AB  - In response to its specific recruitment needs, Walsall teaching primary care
      trust has implemented a new final placement programme for community nursing
      students that focuses on providing students with hands-on experience in the
      community setting. This article presents the results of an evaluation of the
      programme. Outcomes of the programme are discussed and analysis is drawn from all
      key participants. This has been the first stage of a career pathway for 80% of
      these students, who are now successfully employed as community staff nurses
      within the PCT.

PMID- 16415735
TI  - District nursing support for patients with cancer requiring palliative care.
AB  - Patients with cancer spend the majority of the last year of life at home, with
      district nurses (DNs) as the main care coordinators and providers. However, there
      is a relative lack of empirical work on the DN role in this area. This study used
      qualitative, case-study methods to explore the role of district nurses caring for
      patients with cancer who require palliative care. The study focused on three
      patient cases and the researcher visited each patient with the DN on several
      occasions. The sample was three DNs and the principal data collection methods
      were episodes of participant observation (n=11) and in-depth interviews (n=12).
      The findings suggest that DN role was as linchpin or coordinator of palliative
      care at home. They were the main providers of physical and emotional support for
      the patients and families in this study. The supportive role of the DN involved
      referral to other agencies. Patient and carer preferences impacted on decision
      making and care planning and reaching a compromise was often necessary.

PMID- 16415737
TI  - Nurse prescribing: a delightful surprise.

PMID- 16415736
TI  - Public health 3: Legal regulation of tattooing and body art.
AB  - District nurse Mandy Grey is currently treating a thirteen year old girl who has
      a seriously infected tattoo on her buttock and infected tongue and nipple
      piercing all of which were performed at a local tattoo parlour. The teenager
      wanted the tattoo and piercing as all her friends have had similar body art and
      she felt pressured into having the same. Sister Grey wonders how this ever
      popular and increasingly intimate form of bodily adornment is regulated.

PMID- 16415738
TI  - 'Winter Blues 2006' have arrived with a vengeance.

PMID- 16415739
TI  - Kuwait: first world wealth, third world nursing.

PMID- 16415742
TI  - Analysis of patients' rights: dementia and PEG insertion.
AB  - The decision to provide or withhold artificial feeding in patients with advanced
      dementia presents a multifaceted ethical dilemma. This article analyses the
      issues of rights regarding such patients and explores the ethical principles of
      beneficence, non-maleficence, respect/autonomy, justice and veracity. Evidence
      points strongly to hand-feeding being the method of choice for these patients
      (Finucane et al, 1999; Li, 2002). However, for each case there is no right or
      wrong answer and the physical and psychological wellbeing of the individual
      patient must be taken into account.

PMID- 16415741
TI  - Renal dysfunction in liver cirrhosis.
AB  - Liver cirrhosis is an escalating health problem attributed to numerous causes,
      including an increase in alcohol consumption, morbid obesity and chronic viral
      hepatitis. The circulatory disturbances seen in advanced cirrhosis lead to the
      development of ascites, which often lead to progressive renal impairment or the
      development of hepatorenal syndrome. Furthermore, cirrhotic patients commonly
      experience clinical situations that predispose them to the development of pre
      renal failure, such as dehydration, hypovolaemia, septic shock, or exposure to
      nephrotoxic drugs. This article provides an overview of the main causes of acute
      renal failure in liver cirrhosis and describes the current medical and nursing
      management.

PMID- 16415743
TI  - Clinical Corner: an observation of Bowen's disease in wound care.

PMID- 16415744
TI  - Caring for people with carotid artery rupture.
AB  - In the second of three articles, the authors discuss the care of people with
      carotid artery rupture. Carotid artery rupture is a potentially fatal condition
      that requires swift action on the part of the nurse who is present. The size of
      the rupture and the prognosis for the individual patient determines whether or
      not active resuscitation is undertaken. The multi-professional team should
      decide, in advance of an impending rupture, on the optimum plan of care. Calm,
      careful explanations should be given to patients and relatives and the decision
      regarding resuscitation should be recorded in the patient's notes. In the event
      of unforeseen circumstances where a rupture occurs, an active nursing care plan
      should be instituted and care taken to keep relatives well informed. The
      patient's airway should be kept clear through the use of suctioning, inflation of
      tracheostomy tube cuff and correct positioning. Sedative drugs and palliative
      care may subsequently be necessary. Support and help should be given to all who
      witness or are involved in the care of these patients.

PMID- 16415740
TI  - End-of-life care in end-stage renal disease: renal and palliative care.
AB  - The numbers of patients with end-stage renal disease are growing, with a
      disproportionate increase among those who are elderly, dependent and with
      multiple co-morbidities. More of these patients are choosing to be managed
      conservatively, without dialysis. Palliative provision for these patients within
      UK renal services is limited, but the recent National Service Framework for Renal
      Services (Department of Health, 2005) has promoted service development. However,
      few models of service provision have been described. This article describes a
      retrospective review of a new service for conservatively-managed patients with
      end-stage renal disease. The range and complexity of the health needs of this
      population is demonstrated, and an example of service development described. A
      model of the stages of the conservative pathway and appropriate interventions was
      developed. The absence of research evidence prevented development of formal audit
      standards, and highlighted the urgent need for evaluation of models of care.

PMID- 16415745
TI  - Nurse whose attitude towards drug administration put patients at risk.

PMID- 16415746
TI  - Implementation and clinical audit of alcohol detoxification guidelines.
AB  - This article describes the implementation and clinical audit of alcohol
      detoxification guidelines at the Royal Cornwall Hospital. The progress in
      developing a hospital alcohol strategy as recommended by the Royal College of
      Physicians (2001) is also reviewed. The Clinical Institute Withdrawal Assessment
      for Alcohol (revised) (Sullivan et al, 1989) is used to assess the alcohol
      dependent patient's baseline requirement for their detoxification regimen in the
      first 24 hours of their care. The prevention and treatment of Wernicke's
      encephalopathy by parenteral and oral vitamin supplementation is also given a
      high priority in the guidelines. The clinical audit demonstrates high levels of
      compliance with the guidelines that were used effectively by the nursing and
      medical staff in their care of patients with alcohol withdrawal, with high levels
      of referral to the psychiatric liaison nurse service for brief intervention
      alcohol counselling and referral to community alcohol services.

PMID- 16415747
TI  - Health and safety records.
AB  - Records relating to health and safety risk assessments are vital in informing
      staff of inherent risks and securing the safety of colleagues, patients and the
      general public. In addition, since many of the statutory duties in health and
      safety laws must be complied with 'as far as is reasonably practicable' often the
      only way in which the employer can prove, on a balance of probabilities, that he
      did all that was reasonably practicable is by referring to the records relating
      to risk assessments, etc. If prosecuted by the Health and Safety Executive, the
      employer would find it very difficult to achieve an acquittal in the criminal
      courts, if the records are not present.

PMID- 16415748
TI  - A concept analysis of spirituality.
AB  - According to the holistic model of care, nurses must consider their patients'
      spiritual needs in order to provide total patient care (Govier, 2000). There is
      growing awareness of the contribution that spiritual wellbeing can make to a
      patient's actual and perceived health and quality of life (Chibnall et al, 2002;
      Mount, 2003). Spirituality and spiritual care has gained much momentum in the
      current nursing arena. Draper and McSherry (2002) assert that it has emerged from
      the shadows to occupy a prominent part of contemporary health care. Moreover,
      within the nursing profession, a focus on individuals as biopsychosocial
      spiritual beings is gaining recognition. This notion is based on the premise that
      there should be balance of mind, body and spirit for the maintenance of health in
      a person (Stoll, 1989; Stooter, 1995). However, there is evidence that many
      nurses, including nurse educators, have difficulty with the concept of
      spirituality and consequently, may neglect this aspect of care (Greenstreet,
      1999; McSherry, 2000). The aim of this article is to contribute towards
      clarifying the concept of spirituality.

PMID- 16415749
TI  - Multiple sclerosis: living the reality.
AB  - Multiple sclerosis (MS) is a highly variable and unpredictable disease and is
      considered one of the most life-altering diagnoses a person can receive (Holland
      and Madonna, 2005). The hallmark of this disorder is its unpredictability. This
      article explores the journey one individual (ML) takes from the time that
      seemingly trivial symptoms took on a new and disturbing meaning to the point
      where, as someone newly diagnosed with MS, the potential challenges of the
      journey ahead have to be viewed with realism, optimism, and meaning.

PMID- 16415752
TI  - Evaluation of the Bereavement Risk Index (BRI): a community hospice care
      protocol.
AB  - AIM: to test the validity, reliability and feasibility of using a modified
      version of Parkes' (1993) Bereavement Risk Index (BRI) and bereavement support
      protocol in an Australian home hospice care setting. In addition, the study aimed
      to explore what types of family members are most likely to experience a more
      difficult grief reaction. DESIGN: a prospective, descriptive study was used. One
      hundred and fifty bereaved family members participated. Bereaved family members
      were classified as high, medium or low risk and received a structured bereavement
      support protocol based on their level of risk as measured by the BRI. FINDINGS:
      results indicated that a shorter 4-item version of the BRI was more internally
      consistent than the longer version and demonstrated good predictive validity when
      correlated with outcome measures at 3 months following the patient's death.
      CONCLUSION: the modified 4-item BRI demonstrated acceptable reliability and
      validity and was brief and simple to use. Nurses were able to use the instrument
      with minimal training and were able to adhere to a matched bereavement support
      protocol.

PMID- 16415750
TI  - The art and science of drug administration.

PMID- 16415751
TI  - Providing total patient care: the power of reflection.

PMID- 16415753
TI  - Dying in prison: providing palliative care in challenging environments.
AB  - Prison health care in the UK is currently experiencing a period of change and,
      therefore, there are opportunities for the development of palliative care
      services. Some of the challenges of providing this element of care to dying
      prisoners are highlighted in this article.

PMID- 16415754
TI  - Seeking and using families' views to shape children's hospice services.
AB  - Child and family involvement is key to improving the quality of children's
      hospice services. This article reports on a quality assurance initiative
      undertaken as one component of a clinical governance strategy. Service users
      participated in focus groups followed by lunch to discuss how staff communicated
      with them about their child's care, their family support needs, and how staff
      liaised with other professionals and organizations. There was general
      commendation of hospice services (in-house and community), but parents wished for
      more quantity and consistency with all elements of the care model. There was
      tension between respite and end-of-life care needs. Parents considered that the
      myth of hospices being 'just for death' needed dispelling and wanted other
      professionals to be more aware of its role, and the choice of earlier referral.
      Transition, both age and prognosis related, caused concern, with anxiety about
      long-term future or loss of support when prognosis improved. Parents also wanted
      better information about practical help and psycho-social support as well as up
      to-date information about their child's treatment and management from all care
      providers.

PMID- 16415755
TI  - Bereavement and palliative care in China.

PMID- 16415756
TI  - Nursing documentation: non-physical dimensions of end-of-life care in acute
      wards.
AB  - AIM: to explore discrepancies between nurses' knowledge and their documentation
      of issues of psychosocial, spiritual and cultural aspects of palliative care,
      evidenced clearly in recent nursing research into end-of-life care in an acute
      care, teaching hospital. DESIGN: the study involved a retrospective patient case
      note audit of an opportunistic sample of 20 patients deceased recently and
      interviews of the two nurses most involved in the care of each patient (n=40).
      FINDINGS: this research indicates that nurses in acute care settings often
      recognize, sometimes explore, but infrequently document psychosocial, spiritual
      and cultural aspects of care. CONCLUSION: there is a strong need for: (1)
      education about both the impact of non-physical dimensions of patients' lives and
      the effective documentation of these dimensions; and (2) up-grading of
      documentation tools to better facilitate documentation of non-physical aspects of
      palliative care.

PMID- 16415757
TI  - Bridging the specialist-generalist divide: a creative Master's programme
      initiative.
AB  - This article outlines the development of a new Master's programme that is
      suitable particularly for those who are interested in managing palliative care in
      generalist care contexts. Disseminating the essence of excellent palliative care
      provision, accessible by the minority to the majority in need, has been an issue
      for some time. National Service Frameworks identify the contribution of both
      education and workforce planning to facilitate such provision. A gradual shift in
      design of palliative programme provision has seen the emergence of education that
      is more malleable to varied practice contexts. This new MSc Palliative Care
      Programme is centred on interprofessional education, and through collaborative
      working, shares modules with a neighbouring university to produce financially
      viable provision. Essential palliative content is delivered in compulsory taught
      modules, however, elective options include open or work-based modules that
      facilitate palliative practice development tailored to specific context need.
      Postgraduate study, associated with leading practice, means that a few key staff
      can significantly impact disseminating enhanced palliative practice across care
      environments. In this way, in the community and in institutions where the
      majority of older people dying of chronic illness are cared for, resources can be
      used purposefully to maximize the chance of 'a good enough death' (McNamara,
      2001).

PMID- 16415758
TI  - Is fear of death itself a rational preoccupation?

PMID- 16415759
TI  - An aged people is wandering in the desert of ignorance: the land of elderly
      patients with diabetes mellitus.

PMID- 16415760
TI  - A new challenge for diabetologists and geriatricians!
AB  - The "Societe Francaise de Geriatrie et Gerontologie" (SFGG) and "Association de
      Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques" (ALFEDIAM)
      have decided to join their efforts in actions to improve the management and
      treatment of the elderly diabetic patients. New knowledge brought by the
      fundamental research in the domains of longevity genes made possible to discover
      genetic ways, like IGF-1 (insulin-like growth factor 1) which play a regulating
      role between adequacy of the external food availabilities and nutritional body
      needs. Others discovery in the field of the epigenetic regulation of the
      nutrition have consequences on pathology such as the metabolic syndrome. New
      therapeutic prospects and a better definition of the clinical feature will allow
      better prevention and management in prediabetic patients.

PMID- 16415761
TI  - Caring the elderly diabetic patient with respect to concepts of successful aging
      and frailty.
AB  - Successful aging and frailty are emerging constructs becoming necessary to define
      prevention and treatment goals in elderly subjects. Frailty corresponds to the
      stages between full autonomy or successful aging and irreversible functional
      dependency or pathological aging. However its definition is imprecise and
      potential clinical criteria are numerous and interrelated. Diabetes decreases the
      likelihood for successful aging and particularly increases the risk for
      functional dependency. One major end-point in the care of elderly diabetic
      subjects is to investigate the impact of blood glucose control on progression of
      disability. Geriatric intervention based on comprehensive geriatric assessment
      (CGA) in the frail elderly population has been shown effective to prevent the
      loss of autonomy and to improve quality of life, but seems ineffective on
      mortality. It is now recommended to screen elderly diabetic patients for frailty
      criteria. The effect of combined individualized diabetes care and CGA on the
      aging profile should be investigated.

PMID- 16415762
TI  - Insulin resistance: a contributing factor to age-related muscle mass loss?
AB  - Structural and functional modifications occur in skeletal muscle during aging.
      These defects lead to impairment in muscle strength, contractile capacity and
      performance. Among factors implicated in this age-related loss of muscle mass, a
      dysregulation of protein synthesis and breakdown has frequently been reported.
      Insulin plays a major role in regulating muscle protein metabolism, since its
      action contributes to increase net gain of muscle protein in animal and humans.
      More recently, specific actions of insulin on various muscle proteins, notably
      mitochondrial proteins, have been demonstrated, suggesting that insulin is also a
      major regulating factor of mitochondrial oxidative phosphorylation in human
      skeletal muscle. Insulin resistance develops with aging, classically involving
      changes in glucose tolerance. However, the effect of insulin on protein
      metabolism is less well documented, and insulin resistance could be involved in
      age-related muscle protein loss, progressively leading to sarcopenia. Therefore
      in a more general concept, insulin resistance found in many clinical settings,
      could be considered as a contributor to muscle wasting.

PMID- 16415763
TI  - Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin
      secretion?
AB  - Elderly people are more glucose intolerant and insulin resistant than young
      individuals, and many of them will develop type 2 diabetes. It remains, however,
      controversial whether this decrease in function is due to an inevitable
      consequence of "biological aging" or due to environmental or lifestyle variables.
      Indeed, increased adiposity/altered fat distribution, decreased fat free
      mass/abnormal muscle composition, poor dietary habits and physical inactivity all
      contribute to reduce insulin sensitivity. Insulin resistance in elderly people
      appears to predominate in skeletal muscle, whereas hepatic glucose output seems
      to be almost unaffected. Several abnormalities in islet beta-cell and insulin
      secretion were also pointed out in elderly people such as increased amyloid
      deposition and decreased amylin secretion, impaired insulin secretion
      pulsatility, decreased insulin sensitivity of pancreatic beta-cells to
      insulinotropic gut hormones and diminished insulin response to non-glucose
      stimuli such as arginine. Controversial results were reported concerning the
      effects of aging on absolute insulin secretion in response to oral or intravenous
      glucose. However, insulin secretion appears to decrease with age, with
      significantly diminished beta-cell sensitivity and acute insulin response to
      glucose, provided it is analyzed relative to concomitant decreased insulin
      sensitivity. Thus, there is an interplay between decreased insulin secretion and
      increased insulin resistance that largely explains the abnormal glucose
      metabolism seen in elderly. Weight loss, especially reduction of abdominal
      adiposity, and increased physical activity may contribute to improve insulin
      sensitivity and glucose tolerance, and prevent the development of type 2 diabetes
      in elderly people.

PMID- 16415764
TI  - Burden of diabetes in an aging population: prevalence, incidence, mortality,
      characteristics and quality of care.
AB  - The purpose of this work is to review the recent publications on prevalence,
      incidence, mortality, characteristics and quality of care related to diabetes in
      the elderly population. In France, the prevalence of drug-treated diabetes peaks
      at 14% by age 75-79 years, and at least one million people aged over 65 years
      have diabetes. Incidence rates for Northern Europeans rank between 3 and 7 per
      1,000 person-years. The World Health Organization expects prevalent cases to
      further increase, due to better case ascertainment, better survival of people
      with diabetes, increase in obesity leading to a true increase in diabetes
      incidence, and, in developed countries, the important impact of population aging.
      The burden of diabetes in the elderly population is already high. Even in the
      oldest age-groups, excess mortality risks associated with diabetes are
      significant and mostly related to cardiovascular disease, accounting for the loss
      of 3 to 6 years of life. The cardiovascular risk of elderly people with diabetes
      is poorly controlled, increasing risks of diabetes complications, loss of
      cognitive functions and mobility, and dependency. Screening for lipid
      abnormalities and diabetes complications to prevent further damage is
      insufficient, and antihypertensive and hypolipidemic treatments are, in this
      population, underused, as in other countries. Specific adjustments of medical
      nutrition therapy are lacking. In long-term care facilities where the prevalence
      of diabetes is especially high (8 to 25%), quality of diabetes care is often
      poorer. As the burden of diabetes is becoming heavier, specific monitoring of the
      health, quality of care and needs of elderly people with diabetes is required for
      adequate public health planning.

PMID- 16415765
TI  - Hypoglycaemia in elderly diabetic patients.
AB  - Occurring in the elderly diabetic patients, hypoglycaemia may have serious
      consequences in terms of morbidity and mortality, but this severe prognosis is
      nowadays less frequently observed. The clinical manifestations may be somewhat
      different from those observed in young subjects: symptoms are less frequent,
      generally neurologic manifestations. The rate of severe hypoglycaemia remains low
      (about 1.4 episode per 100 patient-years), but increases rapidly in the very
      elderly and also with insulin therapy, co-morbid conditions especially renal
      insufficiency, and associated treatments, as well as with unawareness of
      symptoms. Prevention requires reinforced education for the patient and caregiver,
      particularly concerning diet, knowledge of signs of hypoglycaemia, and
      appropriate treatment. Self-monitoring of blood glucose, by the patient when
      possible, or by a familial or medical caregiver, should be encouraged in order to
      detect asymptomatic episodes of hypoglycaemia and better adapt antidiabetic
      treatment.

PMID- 16415766
TI  - Plasma glucose goals and therapeutic management in elderly diabetic patients.
AB  - In the elderly diabetic patient, therapeutic decision making is not entirely
      based on evidence acquired from large-scale studies conducted in young adults. In
      this population autonomy, co-morbidity and prognosis are all objective parameters
      which must be taken into consideration. Frail patients run the risk of
      hypoglycaemia if the therapeutic goal is too strict. Frail patients can be
      distinguished from autonomous patients free of serious co-morbidity using
      evaluation scales validated for geriatric patients enabling the establishment of
      appropriate goals for the treatment of diabetes without compromising the
      patients' quality-of-life.

PMID- 16415767
TI  - Diabetic hyperosmolarity: a consequence of loss of autonomy.
AB  - Diabetic hyperosmolarity is a serious acute metabolic disorder mainly occurring
      in the frail elderly subject presenting age-related favoring factors (reduced
      sensation of thirst, altered endocrine regulation), disease-related favoring
      factors (cognitive impairment, poor nutritional status and/or loss of autonomy),
      and a triggering factor, generally infection. Diabetic hyperosmolarity can occur
      in a previously non-diabetic patient. Intense dehydration dominants the clinical
      picture. The prognosis depends largely on the underlying chronic disease.

PMID- 16415768
TI  - Mitochondrial function, energy expenditure, aging and insulin resistance.
AB  - Mitochondria are the cells' powerhouse that produce the ubiquitous energy
      currency (ATP) by consuming oxygen, producing water and building up the proton
      motive force. Oxygen consumption is a classical means of assessing energy
      expenditure, one component of energy balance. When energy balance is positive,
      weight increases. This is observed during the dynamic phase of obesity, and
      during body composition changes associated with aging. Whether intrinsic defaults
      in mitochondria occur is the matter of this review. Indeed, the ratio of ATP over
      oxygen consumed, which is not fixed, is one way of regulating heat release and
      ATP flux, but can also be the consequence of environmental conditions of
      mitochondrial work. For example, various hormones (T3, glucocorticoids), changes
      in lipid membrane composition, changes in food intake and exercise, and various
      drugs, can modify the ratio of ATP over oxygen consumed. Aging and insulin
      resistance are other regulators of this ratio. Finally there is a rising body of
      evidence linking diabetes to mitochondrial functions.

PMID- 16415769
TI  - Management of dyslipidemia in elderly diabetic patients.
AB  - The prevalence of diabetes increases with age, potentially affecting 20% of the
      75 years and older elderly population. Overmortality and increased cardiovascular
      morbidity-mortality are common in diabetic populations, including elderly
      diabetes. This increased cardiovascular risk must therefore be taken into
      consideration when discussing management of dyslipidemia in elderly diabetics.
      Should dyslipidemia be treated in elderly diabetics? What are the objectives and
      with what means? Whether the significance of dyslipidemia is different in this
      growing population compared with younger subjects remains unknown due to the lack
      of specific studies. The only results available come from a few primary or
      secondary cardiovascular prevention trials using statins or fibrates with
      subgroups of elderly diabetic patients, or subgroups of diabetic patients and
      also subgroups of patients aged over 65. Three recent studies detailed the
      potential benefit of such treatment: PROSPER in elderly subjects aged 70-82
      years, HPS in diabetics before and after the age of 70 years and CARDS in
      diabetics aged up to 75 years. The results of these studies provide a few
      indirect elements of interest, keeping in mind the generally higher iatrogenic
      risk of treatment in elderly populations.

PMID- 16415771
TI  - The brain of the elderly diabetic patient.
AB  - All available estimations agree that the French population is aging and that the
      proportion of diabetics in the elderly population is increasing. The prevalence
      of diabetes could be about 10% in the over 65 y population. The fact that
      diabetes has an effect on brain function is widely accepted, but there are very
      few studies providing pertinent details. Diabetes is known to affect brain
      function, potential consequences including cognitive decline, dementia,
      depression, and stroke. These complications are frequently associated, leading to
      poor quality-of-life with considerable social and economic impact. While the
      results of different studies can be contradictory, there is an overall trend
      towards the conclusion that diabetes, often associated with high blood pressure,
      contributes to cognitive decline in elderly diabetics as well as to an increased
      frequency and severity of cerebral vascular events. These considerations point
      out the importance of proper management of diabetes in the elderly population and
      the need for cooperative studies to determine the role of diabetes and different
      cardiovascular risk factors in the development of dementia, stroke, and
      depressive syndromes whose consequences are probably underestimated.

PMID- 16415770
TI  - Management of hypertension in elderly diabetic patients.
AB  - Hypertension is a major vascular risk factor in the elderly diabetic. The benefit
      of proper management is well recognized, even if treatment has no influence on
      overall mortality or might even tend to increase it in very elderly subjects.
      Globally, the efficacy of the major classes of antihypertensive drugs, diuretics,
      beta-blockers, calcium channel blockers, angiotensin converting enzyme
      inhibitors, or angiotensin II receptor antagonists appears to be equivalent so
      that the therapeutic choice depends on the type of hypertension, systolic or
      systolic-diastolic, and the rapidity of the desired effect, co-morbid conditions,
      particularly coronary or renal disease, or drug tolerance. Blood pressure goals
      are similar to those in middle-aged persons, except in very old, frail or sick
      subjects.

PMID- 16415773
TI  - Diabetes in the elderly: considerations for clinical practice.

PMID- 16415772
TI  - Use of antidiabetic drugs in elderly patients.
AB  - The objective of this review of the literature is to analyze the results of
      studies including diabetic patients aged 70 years and older. Although the risk of
      treatment is greater in this population because of co-morbid conditions and
      altered renal function, information on the pharmacokinetics and pharmacodynamics
      of antidiabetic drugs remains limited. Long-term experience with sulfonylureas is
      sufficient to establish certain general rules of use; but for biguanides and
      alpha-glucosidase inhibitors, problems of tolerance limit use; further data are
      needed on glinides and glitazones. Use of insulin or insulin analogs is frequent
      and prescription should be adapted to achieve an acceptable balance between the
      risk of hypoglycaemia and therapeutic goals.

PMID- 16415774
TI  - [Journal de Radiologie: even more!].

PMID- 16415775
TI  - [Imaging of salivary lithiasis].
AB  - Lithiasis is the most common disease of salivary glands after mumps. The purpose
      of this review is to analyze the respective role of the different available
      imaging techniques for the diagnosis of lithiasis and related complications since
      the treatment of salivary lithiasis has evolved with the emergence of minimally
      invasive and non surgical techniques. In spite of its limitations, US represents
      an excellent first line imaging technique because it is non-invasive and widely
      available. Non contrast helical CT with multiplanar reconstructions seems to be
      the gold standard for the diagnosis of lithiasis, especially when small and
      poorly calcified since these may not be visible on standard radiographs. CT
      allows accurate characterization of the number and position of lithiasis. MR
      Sialography is increasingly replacing the more invasive conventional sialography
      for the non invasive visualization of the ductal system of major salivary glands
      even though conventional sialography has a higher spatial resolution.

PMID- 16415777
TI  - [Value of vacuum assisted biopsies under sonography guidance: results from a
      multicentric study of 650 lesions].
AB  - OBJECTIVE: With this retrospective, multi-centric study, the authors are showing
      the technique of Vacuum assisted biopsies under ultrasound guidance and comparing
      it with the other widely used diagnostic techniques. Material and method. Six
      hundred and fifty biopsies were performed between May 2000 and December 2004, on
      644 patients, in 3 centres, following a unique protocol. Lesions were
      categorized, using the classification from Stavros, between "probably benign",
      "indeterminate", "probably malignant" and "malignant" Histology was validated
      only after review of the clinical and radiological data, as well as surgical data
      when available. All benign cases were included in an on-going follow-up protocol.
      RESULTS: We have identified 471 benign lesions and 179 malignant lesions. The
      mean size of the lesions was 9 mm. Three cancers were diagnosed in the cases of
      "probably benign lesions" and in the cases of "probably malignant lesions" 18
      (27%) were inflammatory disorders. In 5 cases vacuum biopsy underestimated the
      pathology with regard to surgery: 2 cases of atypical duct hyperplasia (HCA) were
      in situ ductal carcinoma (DCIS) at surgery and 3 cases of DCIS were infiltrative
      ductal carcinoma (DCI) at surgery. With this technique we have avoided surgery
      for 71% of all women who presented an "indeterminate" or "probably malignant"
      condition. Specificity is excellent with no cancer detected so far among the
      patients with benign findings, under follow-up. CONCLUSION: Ultrasound guided
      Vacuum assisted biopsy is a fairly recent minimally invasive technique, with
      short learning curve. The ability to collect a larger volume of tissue overcomes
      the targeting issues on small lesions and avoids underestimation of heterogeneous
      and larger abnormalities and some specific at-risk lesions such as papilloma.
      This technique thus appears indicated in such cases because it overcomes some of
      the limitations of core needle biopsy and should be considered as an alternative
      to surgical biopsy.

PMID- 16415778
TI  - [Discoid menisci in children: ultrasonographic features].
AB  - OBJECTIVE: Discoid meniscus is a rare congenital pathology affecting mainly the
      lateral meniscus. Radiological diagnosis, initially based on arthrographic
      findings, is now established on well defined MRI criteria. In this study,
      ultrasonography (US) was the modality proposed for diagnosing discoid meniscus
      and compared to the normal sonographic meniscal pattern. Subjects and methods. 8
      children aged from 6 to 11 years, with a symptomatology highly suggestive of
      meniscal pathology, were investigated by US of both knees, followed by MRI in 3
      and arthroscopy in all cases. RESULTS: In all 8 cases, a meniscus was diagnosed
      as discoid when it no longer had its normal triangular shape, was abnormally
      elongated and thick and demonstrated a heterogeneous central pattern. Associated
      lesions (fracture, cystic degeneration) were well demonstrated on US. The lateral
      meniscus was involved in all 8 cases, the pathology was bilateral in 5 cases and
      MRI/US correlation was good in 3 cases. Arthroscopy confirmed US findings in all
      cases. CONCLUSION: US, a more widely available imaging modality, is a reliable
      technique for the diagnosis of discoid meniscus in children.

PMID- 16415776
TI  - [Vascular tumours and malformation of the orbit].
AB  - Vascular diseases are an important part of orbital pathology. We describe
      vascular tumours of the orbit and vascular diseases with repercussion on the
      orbit, from intra or extra orbital origin. The classification of these
      abnormalities is difficult and several terms are used to describe the same
      histological entity. The objective of this work is, using the current
      classification, to illustrate the different imaging aspects of the most frequent
      vascular diseases of the orbit.

PMID- 16415779
TI  - [Mangafodipir trisodium-enhanced magnetic resonance cholangiography for detection
      of bile leaks].
AB  - PURPOSE: To assess the value of contrast-enhanced magnetic resonance
      cholangiography with Teslascan perfusion for the detection and localization of
      trauma-induced and postoperative bile leaks. MATERIALS AND METHODS: Between
      October 2002 and December 2004, 7 patients with suspected bile duct leaks after
      trauma (n = 2) or surgery (n = 5) requiring morphological evaluation were
      included. MRI examination included single shot fast spin- echo T2 weighted and
      gradient echo T1 weighted images prior to and 112 minutes in average after IV
      administration of mangafodipir trisodium. The results of contrast enhanced MR
      cholangiography were correlated to surgery (n = 3), clinical course (n = 3) and
      percutaneous drainage (n = 1). RESULTS: Mangafodipir trisodium-enhanced imaging
      showed extravasated Teslascan in collections in 6 patients (86%) whereas the
      combination of T2 weighted images and mangafodipir trisodium enhanced images
      revealed biliary collections in 7 patients (100%). The fistula between bile duct
      and collection was visualized in 4 patients (57%) before mangafodipir trisodium
      perfusion and in 3 patients (43%) after injection. In one patient the fistula was
      visible only after injection. Combination of both pre- and post injection MR
      correctly depicted the origin of bile leak in 5 cases (71%). CONCLUSION:
      Mangafodipir trisodium-enhanced magnetic resonance cholangiography is a non
      invasive technique that can successfully detect the presence of bile duct leaks.
      The combination of T2 weighted MR cholangiography and mangafodipir trisodium
      enhanced T1 weighted MR cholangiography increases the sensitivity in detection
      and localization of the site of bile leak.

PMID- 16415780
TI  - [Sonographic cerebral sulcal pattern in normal fetuses].
AB  - PURPOSE: Define normal sulcation patterns and their chronological order of
      appearance on transabdominal ultrasound by comparing them with brain maturation
      references available in fetopathological studies and MRI findings. PATIENTS AND
      METHODS: By means of a prospective study, 158 normal fetal brains aged 21 to 34
      gestational weeks have been analyzed with standardized data by transabdominal
      ultrasound in eleven different views using axial, coronal and sagittal
      orientation. RESULTS: The sequential development of cerebral sulci has been
      described according to the gestational age. This chronology was consistent with
      anatomo-pathologic references presenting a mean late period of one week and with
      MRI but without any late period. This study is available on the following
      website: CONCLUSION: This ultrasound study provides accurate landmarks and
      imaging features of normal fetal brain sulcation. The analysis and the knowledge
      of this sulcation provide better understanding of the brain cortex maturation and
      may be helpful in diagnosing brain diseases.

PMID- 16415782
TI  - [Unusual location of a parathyroid adenoma: the carotid sheath].
AB  - We report the imaging features of an occult parathyroid adenoma with unusual
      location in the carotid sheath. Our patient presented with primary
      hyperparathyroidism. Following negative neck ultrasound and scintigraphy,
      exploratory neck dissection with partial thyroidectomy was performed twice over a
      2 day period without biological response. Cervical and mediastinal CT and MRI
      were performed with no result. Digital angiography showed a tumoral blush
      supplied by the left inferior thyroid artery and located in close contact with
      the carotid artery. Venous sampling of the neck confirmed the left location of
      the adenoma and a third surgical intervention found the adenoma embedded in the
      left carotid sheath. This is an unusual case of parathyroid adenoma that
      necessitated the use of several imaging techniques.

PMID- 16415781
TI  - [Isolated congenital left ventricular diverticulum: report of a paediatric case].
AB  - Congenital cardiac diverticulum is a rare malformation formed by an outpouching
      of the ventricular wall, in particular the left ventricle. The thoraco-abdominal
      type is more frequent than the isolated thoracic type. Topographical and imaging
      considerations regarding an isolated congenital left ventricular diverticulum
      incidentally discovered in a 9-year-old-boy are reviewed.

PMID- 16415783
TI  - [Occipital osteosarcoma of a 33 years old man: a case report].
AB  - Cranial localization of osteosarcoma is rare, representing only 0,7-3% of cranial
      primary tumours. The authors present the case of a 33 year old man with occipital
      osteosarcoma diagnosed by CT scan, MRI and angiography. The radiological features
      of this pathology are discussed.

PMID- 16415784
TI  - [Isolated synovial chondromatosis of the subacromial bursa: report of a new case
      and review of the literature].
AB  - Synovial chondromatosis is a rare metaplasia of the synovium of unknown etiology
      that may involve occasionally the subacromial bursa. We report a new case
      diagnosed by ultrasound in a 30-year-old man and we present pathogenetic,
      diagnostic and therapeutic features of this disease with a literature review.

PMID- 16415785
TI  - [Gastroduodenal intussusception complicating Menetrier's disease].
AB  - The authors report a very rare case of gastroduodenal intussusception
      complicating Menetrier's disease. This uncommon condition of unknown aetiology is
      characterized by hyperplasia of the gastric mucosal folds. Computed Tomography
      (CT) in high resolution mode can be helpful for diagnosis by showing the
      cerebriform surface of the giant mucosal folds. Filling the gastoduodenal tract
      with water is useful in non complicated cases.

PMID- 16415786
TI  - [Atypical back pain].

PMID- 16415787
TI  - [Consensus recommendations from the French Society of Radiology and French
      Society of Cardiology for appropriate management of patients requiring CT or
      MRI].

PMID- 16415790
TI  - Maintenance of plastid RNA editing activities independently of their target
      sites.
AB  - RNA editing in plant organelles is mediated by site-specific, nuclear-encoded
      factors. Previous data suggested that the maintenance of these factors depends on
      the presence of their rapidly evolving cognate sites. The surprising ability of
      allotetraploid Nicotiana tabacum (tobacco) to edit a foreign site in the
      chloroplast ndhA messenger RNA was thought to be inherited from its diploid male
      ancestor, Nicotiana tomentosiformis. Here, we show that the same ndhA editing
      activity is also present in Nicotiana sylvestris, which is the female diploid
      progenitor of tobacco and which lacks the ndhA site. Hence, heterologous editing
      is not simply a result of tobacco's allopolyploid genome organization. Analyses
      of other editing sites after sexual or somatic transfer between land plants
      showed that heterologous editing occurs at a surprisingly high frequency. This
      suggests that the corresponding editing activities are conserved despite the
      absence of their target sites, potentially because they serve other functions in
      the plant cell.

PMID- 16415788
TI  - Tudor, MBT and chromo domains gauge the degree of lysine methylation.
AB  - The post-translational modification of histones regulates many cellular
      processes, including transcription, replication and DNA repair. A large number of
      combinations of post-translational modifications are possible. This cipher is
      referred to as the histone code. Many of the enzymes that lay down this code have
      been identified. However, so far, few code-reading proteins have been identified.
      Here, we describe a protein-array approach for identifying methyl-specific
      interacting proteins. We found that not only chromo domains but also tudor and
      MBT domains bind to methylated peptides from the amino-terminal tails of histones
      H3 and H4. Binding specificity observed on the protein-domain microarray was
      corroborated using peptide pull-downs, surface plasma resonance and far western
      blotting. Thus, our studies expose tudor and MBT domains as new classes of methyl
      lysine-binding protein modules, and also demonstrates that protein-domain
      microarrays are powerful tools for the identification of new domain types that
      recognize histone modifications.

PMID- 16415789
TI  - Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+
      oscillations.
AB  - Although many cell functions are regulated by Ca(2+) oscillations induced by a
      cyclic release of Ca(2+) from intracellular Ca(2+) stores, the pacemaker
      mechanism of Ca(2+) oscillations remains to be explained. Using green fluorescent
      protein-based Ca(2+) indicators that are targeted to intracellular Ca(2+) stores,
      the endoplasmic reticulum (ER) and mitochondria, we found that Ca(2+) shuttles
      between the ER and mitochondria in phase with Ca(2+) oscillations. Following
      agonist stimulation, Ca(2+) release from the ER generated the first Ca(2+)
      oscillation and loaded mitochondria with Ca(2+). Before the second Ca(2+)
      oscillation, Ca(2+) release from the mitochondria by means of the Na(+)/Ca(2+)
      exchanger caused a gradual increase in cytoplasmic Ca(2+) concentration, inducing
      a regenerative ER Ca(2+) release, which generated the peak of Ca(2+) oscillation
      and partially reloaded the mitochondria. This sequence of events was repeated
      until mitochondrial Ca(2+) was depleted. Thus, Ca(2+) shuttling between the ER
      and mitochondria may have a pacemaker role in the generation of Ca(2+)
      oscillations.

PMID- 16415791
TI  - Histological types and significance of bronchial epithelial dysplasia.
AB  - Pulmonary epithelium is known to undergo a preneoplastic process prior to the
      development of lung carcinoma. Squamous dysplasia and atypical adenomatous
      hyperplasia have been identified and classified as preinvasive lesions of
      squamous cell carcinoma and peripheral pulmonary adenocarcinoma, respectively.
      However, these commonly recognized preinvasive lesions do not completely explain
      the development of all histological types of lung carcinoma. By examining 114
      resection lung specimens, we concluded that there are four histological patterns
      of bronchial epithelial dysplasia based on morphological features (basal cell
      dysplasia, columnar cell dysplasia, bronchial epithelial dysplasia with
      transitional differentiation, and squamous dysplasia). The histological patterns
      were further characterized by immunohistochemistry. Basal cell dysplasia was
      focally positive for cytokeratin (CK) 17 and 10/13; columnar cell dysplasia was
      generally positive for CK7, 8, and 18; bronchial epithelial dysplasia with
      transitional differentiation had a heterogeneous immunoprofile, while squamous
      dysplasia was positive for CK10/13 and focally positive for CK17. Various degrees
      of abnormal expression of p53 and Ki-67 were found in the different types of
      bronchial epithelial dysplasia. The cases were divided into three groups based on
      degree and extent of bronchial epithelial dysplasia. By Crosstabs McNemar test,
      the Mann-Whitney U-test (for two independent groups), the Kruskal-Wallis one-way
      nonparametric ANOVA (for >2 independent groups) and Spearman correlation
      analysis, the degree and extent of bronchial epithelial dysplasia was shown to be
      positively correlated with the incidence of bronchogenic carcinoma and multifocal
      primary lung carcinoma (P<0.05). These findings indicated the following: (1)
      bronchial epithelium can develop various patterns of dysplasia with
      abnormal/ambiguous cell differentiation and abnormal expressions of p53 and Ki
      67. Thus, these bronchial epithelial dysplastic lesions may represent a
      preneoplastic process. (2) The degree of bronchial epithelial dysplasia may
      significantly predispose individuals to bronchogenic carcinoma and multifocal
      primary lung carcinoma.

PMID- 16415792
TI  - Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in
      cervical low-grade lesions.
AB  - The p16(INK4a) is a cyclin-dependent kinase inhibitor that decelerates the cell
      cycle by inactivating the cyclin-dependent kinases involved in the
      phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7
      oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16
      pathway, leads to p16 upregulation. Although it is widely reported that p16 is
      overexpressed in a high percentage of preneoplastic lesions and in almost all
      carcinomas of the uterine cervix, protein upregulation and its correlation with
      HPV infection in low-grade lesions is still being debated. In this study, we
      investigated in parallel, p16 expression and HPV infection in 100 cervical
      biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous
      cancers). Results obtained demonstrated that none of the 17 normal cervical
      tissues, evaluated by immunohistochemistry, presented p16 positivity whereas,
      starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a
      constant and significant increase of protein overexpression (P<0.0001) was
      observed. In addition, p16 overexpression consistently showed elevated
      sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high
      positive predictive value (97%) and negative predictive value (86%). Of interest,
      93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed
      that p16 overexpression is associated to high-grade precancerous lesions and
      cervical carcinomas, and further demonstrated that immunohistochemical evaluation
      of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade
      lesions.

PMID- 16415793
TI  - Local recurrence of myxofibrosarcoma is associated with increase in tumour grade
      and cytogenetic aberrations, suggesting a multistep tumour progression model.
AB  - Myxofibrosarcoma is one of the most frequent soft tissue tumours in elderly
      patients, mostly arising in the extremities. Grade I lesions are only locally
      aggressive whereas grade II and grade III lesions have metastatic potential. The
      differential diagnosis contains several other (benign) myxoid soft tissue
      tumours. A number of sarcomas are characterised by specific cytogenetic
      aberrations, giving not only insight in their biological pathways; they also
      serve as molecular markers in difficult diagnoses. Cytogenetic data on
      myxofibrosarcoma are scarce with only few isolated cases described in the
      literature. No specific chromosomal aberrations have been detected so far.
      Moreover, molecular pathways in tumorigenesis and progression of myxofibrosarcoma
      are barely understood. We studied the clinicopathologic data and karyotypes of 32
      myxofibrosarcomas using conventional banding and multicolour COmbined Binary
      RAtio labelling fluorescence in situ hybridisation technique. We included eight
      grade I, eight grade II and 16 grade III lesions. In all, 22 were primary
      tumours, nine were local recurrences and one a lymph node metastasis. The
      myxofibrosarcomas showed equal sex distribution, were mostly located at the
      extremities with two thirds deep-seated and had an average age of occurrence of
      66 years. We found normal karyotypes in eight cases and clonal beside nonclonal
      aberrations in 22 cases. Complex cytogenetic anomalies were found in all grades.
      However, no tumour-specific chromosomal abnormalities could be withdrawn. Local
      recurrences showed increase in grade compared to their primary lesions.
      Interestingly, these recurrences showed more complex cytogenetic aberrations.
      Increase in grade seems to parallel increase in cytogenetic aberrations and
      malignant potential. Since the chromosomal aberrations found were not tumour type
      specific, they seem to be rather the result of secondary events in tumour
      progression and tumour genetic instability. Based on these findings, we suggest
      that tumorigenesis of myxofibrosarcoma is mainly a multistep genetic process,
      probably ruled by genetic instability caused by targeted checkpoint genes.

PMID- 16415794
TI  - The diagnostic utility of immunohistochemistry in distinguishing between
      epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative
      study.
AB  - As both mesotheliomas and squamous carcinomas can present a wide variety of
      morphological patterns, they can on occasion be confused. Recently, some groups
      of investigators have called attention to the difficulties that sometimes exist
      in distinguishing between these malignancies and the need to define a panel of
      markers that can assist in reaching the correct diagnosis. The aim of the present
      study is to compare the value of the various immunohistochemical markers
      currently available for the diagnosis of mesothelioma and squamous carcinoma of
      the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or
      predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the
      lung were investigated for the expression of the following markers: podoplanin,
      calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic
      antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis(y)), leu-M1 (CD15), and
      thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas
      reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1
      and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for
      B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were
      positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8,
      77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27%
      for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing
      the results, it is concluded that from a practical point-of-view, a combination
      of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two
      negative mesothelioma markers (p63 and MOC-31) would allow the differential
      diagnosis to be established between epithelioid mesotheliomas and squamous
      carcinomas of the lung in nearly all instances.

PMID- 16415796
TI  - Older oral health.

PMID- 16415795
TI  - Calretinin, CD34, and alpha-smooth muscle actin in the identification of
      peritoneal invasive implants of serous borderline tumors of the ovary.
AB  - The correct identification of invasive implants in the peritoneum in serous
      borderline tumors (SBTs) of the ovary is an important determinant of diagnosis,
      treatment, and prognosis. Although the histologic criteria to distinguish
      noninvasive from invasive implants have been defined, the distinction can still
      be difficult. We examined the presence and distribution of mesothelial cells,
      stromal fibrocytes, and myofibroblasts in invasive and noninvasive peritoneal
      implants in 100 noninvasive, 100 invasive, and 100 metastatic nests/foci from 20
      cases of SBTs with peritoneal implants, 10 serous carcinomas with peritoneal
      metastasis, and 10 cases of endosalpingiosis by immunostaining for calretinin,
      CD34, and alpha-SMA. All 100 invasive nests from seven SBTs and all 100
      metastatic nests from the cases of serous carcinoma showed loss of calretinin+
      mesothelial cells and stromal CD34+ fibrocytes around the nests. In contrast,
      72/100 noninvasive nests displayed the presence of mesothelial cells around the
      nests and 68 displayed preservation of surrounding stromal fibrocytes. Alpha
      smooth muscle actin positive myofibroblasts were present as a stromal response in
      100/100 metastatic nests, 100/100 invasive nests and 54/100 noninvasive nests.
      The loss of mesothelial cells and stromal fibrocytes surrounding invasive nests
      together with a proliferation of myofibroblasts as demonstrated by immunostaining
      proved to be a sensitive and specific tool to separate invasive from noninvasive
      implants and represents an important adjunct to morphologic diagnosis. Combined
      sensitivity and specificity of the three antibodies was 100 and 81%,
      respectively. These methods, however, may not be helpful for small biopsies of
      noninvasive desmoplastic implants. The distribution of these cells provides some
      insights into the histogenesis of invasive and noninvasive implants in SBTs.

PMID- 16415797
TI  - Restrain or refer?

PMID- 16415798
TI  - Dumbing down dentistry.

PMID- 16415799
TI  - Manpower position.

PMID- 16415800
TI  - No miracles.

PMID- 16415801
TI  - Outside the box.

PMID- 16415802
TI  - Encouraging prognostic sign.

PMID- 16415804
TI  - BADN membership.

PMID- 16415803
TI  - The BDJ is 134.

PMID- 16415805
TI  - Skulduggery in the NHS.

PMID- 16415806
TI  - The burden of proof.

PMID- 16415807
TI  - Exercising the tongue.

PMID- 16415808
TI  - Antibiotic prophylaxis: a myth?

PMID- 16415809
TI  - Women in practice.

PMID- 16415822
TI  - Oral medicine--update for the dental practitioner oral cancer.
AB  - This series provides an overview of current thinking in the more relevant areas
      of oral medicine for primary care practitioners, written by the authors while
      they were holding the Presidencies of the European Association for Oral Medicine
      and the British Society for Oral Medicine, respectively. A book containing
      additional material will be published. The series gives the detail necessary to
      assist the primary dental clinical team caring for patients with oral complaints
      that may be seen in general dental practice. Space precludes inclusion of
      illustrations of uncommon or rare disorders, or discussion of disorders affecting
      the hard tissues. Approaching the subject mainly by the symptomatic approach--as
      it largely relates to the presenting complaint--was considered to be a more
      helpful approach for GDPs rather than taking a diagnostic category approach. The
      clinical aspects of the relevant disorders are discussed, including a brief
      overview of the aetiology, detail on the clinical features and how the diagnosis
      is made. Guidance on management and when to refer is also provided, along with
      relevant websites which offer further detail.

PMID- 16415823
TI  - The role of competence and capacity in relation to consent for treatment in adult
      patients.
AB  - Obtaining informed consent for dental and medical treatment is a fundamental
      ethical and legal responsibility for all clinicians. It is an opportunity for
      patients to have healthcare that is based on their informed choice. The
      assessment of a patient's competence is an essential part of the consent process
      and clinicians need to be aware that patients can be misunderstood and wrongly
      deemed incompetent. This paper aims to aid the clinician to better understand the
      concept of patient competency and capacity in relation to obtaining valid
      consent.

PMID- 16415831
TI  - Sugar and cancer.

PMID- 16415832
TI  - No to chlorhexidine.

PMID- 16415833
TI  - Address the real cause.

PMID- 16415834
TI  - A cephalometric comparison of skulls from the fourteenth, sixteenth and twentieth
      centuries.
AB  - OBJECTIVES: To evaluate changes in the size and shape of the skull and jaws in
      British populations between the thirteenth and twentieth centuries. METHOD:
      Lateral cephalometric radiograms were obtained from skulls of three groups of
      subjects: 30 skulls were from the remains of those who died in the London Black
      Death epidemic of 1348, 54 skulls were recovered from the wreck of the Mary Rose
      which sank in 1545 and 31 skulls were representative of modern cephalometric
      values. RESULTS: Horizontal measurements in the base of the anterior cranial
      fossa and in the maxillary complex were greater in the modern group than in the
      medieval skulls. Cranial vault measurements were significantly higher (P=0.000)
      in the twentieth century skulls, especially in the anterior cranial fossa.
      CONCLUSION: Results suggest that our medieval ancestors had more prominent faces
      and smaller cranial vaults than modern man.

PMID- 16415835
TI  - Dental anxiety, distress at induction and postoperative morbidity in children
      undergoing tooth extraction using general anaesthesia.
AB  - OBJECTIVE: To report on the prevalence of postoperative morbidity in children
      undergoing tooth extraction under chair dental general anaesthetic (CDGA) in
      relation to pre-operative dental anxiety and anaesthetic induction distress.
      DESIGN: A prospective national study. SETTING: Twenty-five Scottish DGA centres
      in 2001. SUBJECTS AND METHOD: Four hundred and seven children (mean age 6.6
      years; range: 2.3 to 14.8 years; 52% male). Before CDGA, the Modified Child
      Dental Anxiety (MCDAS) and Modified Dental Anxiety (MDAS) Scales were completed
      for children and accompanying adult respectively; the latter also returned a
      morbidity questionnaire 24 hours and one week post-operatively. Anaesthetic
      induction distress was scored immediately before CDGA induction using the
      Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The mean
      MCDAS score was 24.2 (population norm 18.2); 21% of adults were anxious. Forty
      two per cent of children had induction distress; this related to their MCDAS
      scores (r=0.43, p<0.001, Pearson Product Moment Correlation Coefficient).
      Morbidity at 24 hours and seven days was 63% and 24% respectively; this related
      to MCDAS scores (r=0.15, p=0.029 and r=0.17, p=0.009, Pearson Product Moment
      Correlation Coefficient) and to induction distress (chi2=7.14, p=0.007 and
      chi2=11.70, p=0.001). CONCLUSION: The majority of children suffered next day
      morbidity and many still had symptoms a week later. Most children were dentally
      anxious; this related to induction distress and postoperative morbidity.

PMID- 16415836
TI  - An investigation of the relationship between untreated decayed teeth and dental
      sepsis in 5-year-old children.
AB  - OBJECTIVES: To investigate the prevalence of dental sepsis in 5-year-old children
      in Scotland and the relationship between sepsis, treated and untreated decayed
      teeth, oral cleanliness (visible plaque on anterior teeth) and socio-economic
      deprivation. SUBJECTS AND METHODS: Six thousand, nine hundred and ninety-four
      children of mean age 5.3 years were examined as part of a survey conducted under
      the Scottish Health Board's Dental Epidemiological Programme. The presence of
      dental sepsis was recorded, in addition to caries status, and presence of plaque.
      Postal code information was used to obtain a measure of material deprivation.
      Relationships between sepsis and its possible contributory factors were explored
      using stepwise logistic regression. MAIN RESULTS: In the whole sample, 4.8% of
      children examined had dental sepsis, ranging from 2% in the most affluent areas
      to 11% in the most deprived. Children with sepsis had much higher caries
      experience (mean dmft 6.30) than those without sepsis (mean dmft 2.36). However,
      when these factors and the presence of plaque were entered into a logistic
      regression model to predict presence or absence of dental sepsis, the most
      important factor was not deprivation, but untreated decay. CONCLUSIONS: The
      proportion of children with sepsis increases markedly with caries experience.
      This disadvantage can be mitigated if more of the caries experience is treated.
      These findings would not support a policy of non-intervention for deciduous
      caries if oral sepsis is to be minimised.

PMID- 16415849
TI  - Tsunami--a first hand account.
AB  - In the first of two reports on the tsunami and its effects, to mark its first
      anniversary, young UK dentist Bob Bhamra describes first hand how and his wife
      Sukhi found themselves caught up in Thailand in the terrifying events of Boxing
      Day 2004.

PMID- 16415852
TI  - Nanospring behaviour of ankyrin repeats.
AB  - Ankyrin repeats are an amino-acid motif believed to function in protein
      recognition; they are present in tandem copies in diverse proteins in nearly all
      phyla. Ankyrin repeats contain antiparallel alpha-helices that can stack to form
      a superhelical spiral. Visual inspection of the extrapolated structure of 24
      ankyrin-R repeats indicates the possibility of spring-like behaviour of the
      putative superhelix. Moreover, stacks of 17-29 ankyrin repeats in the cytoplasmic
      domains of transient receptor potential (TRP) channels have been identified as
      candidates for a spring that gates mechanoreceptors in hair cells as well as in
      Drosophila bristles. Here we report that tandem ankyrin repeats exhibit tertiary
      structure-based elasticity and behave as a linear and fully reversible spring in
      single-molecule measurements by atomic force microscopy. We also observe an
      unexpected ability of unfolded repeats to generate force during refolding, and
      report the first direct measurement of the refolding force of a protein domain.
      Thus, we show that one of the most common amino-acid motifs has spring properties
      that could be important in mechanotransduction and in the design of nanodevices.

PMID- 16415853
TI  - The Dam1 kinetochore ring complex moves processively on depolymerizing
      microtubule ends.
AB  - Chromosomes interact through their kinetochores with microtubule plus ends and
      they are segregated to the spindle poles as the kinetochore microtubules shorten
      during anaphase A of mitosis. The molecular natures and identities of coupling
      proteins that allow microtubule depolymerization to pull chromosomes to poles
      during anaphase have long remained elusive. In budding yeast, the ten-protein
      Dam1 complex is a critical microtubule-binding component of the kinetochore that
      oligomerizes into a 50-nm ring around a microtubule in vitro. Here we show, with
      the use of a real-time, two-colour fluorescence microscopy assay, that the ring
      complex moves processively for several micrometres at the ends of depolymerizing
      microtubules without detaching from the lattice. Electron microscopic analysis of
      'end-on views' revealed a 16-fold symmetry of the kinetochore rings. This out-of
      register arrangement with respect to the 13-fold microtubule symmetry is
      consistent with a sliding mechanism based on an electrostatically coupled ring
      microtubule interface. The Dam1 ring complex is a molecular device that can
      translate the force generated by microtubule depolymerization into movement along
      the lattice to facilitate chromosome segregation.

PMID- 16415854
TI  - Engineered membrane superchannel improves bioremediation potential of dioxin
      degrading bacteria.
AB  - Sphingomonas sp. A1 possesses specialized membrane structures termed
      'superchannels' that enable the direct incorporation of macromolecules into the
      cell. We have engineered two related sphingomonads, the dioxin-degrading S.
      wittichii RW1 and the polypropylene glycol-degrading S. subarctica IFO 16058(T),
      to incorporate this superchannel into their cell membranes. In both cases the
      bioremediation capability of the organisms was substantially increased pointing
      at the potential of this approach as a general strategy to improve bacterial
      degradation of hazardous compounds in the environment.

PMID- 16415855
TI  - Characterization and identification of vaccine candidate proteins through
      analysis of the group A Streptococcus surface proteome.
AB  - We describe a proteomic approach for identifying bacterial surface-exposed
      proteins quickly and reliably for their use as vaccine candidates. Whole cells
      are treated with proteases to selectively digest protruding proteins that are
      subsequently identified by mass spectrometry analysis of the released peptides.
      When applied to the sequenced M1_SF370 group A Streptococcus strain, 68 PSORT
      predicted surface-associated proteins were identified, including most of the
      protective antigens described in the literature. The number of surface-exposed
      proteins varied from strain to strain, most likely as a consequence of different
      capsule content. The surface-exposed proteins of the highly virulent M23_DSM2071
      strain included 17 proteins, 15 in common with M1_SF370. When 14 of the 17
      proteins were expressed in E. coli and tested in the mouse for their capacity to
      confer protection against a lethal dose of M23_DSM2071, one new protective
      antigen (Spy0416) was identified. This strategy overcomes the difficulties so far
      encountered in surface protein characterization and has great potential in
      vaccine discovery.

PMID- 16415856
TI  - G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early
      embryogenesis.
AB  - Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and
      in early embryonic cells, where it has been shown to be important for maintaining
      pluripotency. Following implantation, this gene undergoes a novel multi-step
      programme of inactivation. Transcriptional repression is followed by a pronounced
      increase in histone H3 methylation on Lys 9 that is mediated by the SET
      containing protein, G9a. This step sets the stage for local
      heterochromatinization via the binding of HP1 and is required for subsequent de
      novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show
      that these epigenetic changes actually have an important role in the inhibition
      of Oct-3/4 re-expression, thereby preventing reprogramming.

PMID- 16415857
TI  - The Polycomb group protein Eed protects the inactive X-chromosome from
      differentiation-induced reactivation.
AB  - The Polycomb group (PcG) encodes an evolutionarily conserved set of chromatin
      modifying proteins that are thought to maintain cellular transcriptional memory
      by stably silencing gene expression. In mouse embryos that are mutated for the
      PcG protein Eed, X-chromosome inactivation (XCI) is not stably maintained in
      extra-embryonic tissues. Eed is a component of a histone-methyltransferase
      complex that is thought to contribute to stable silencing in undifferentiated
      cells due to its enrichment on the inactive X-chromosome in cells of the early
      mouse embryo and in stem cells of the extra-embryonic trophectoderm lineage.
      Here, we demonstrate that the inactive X-chromosome in Eed(-/-) trophoblast stem
      cells and in cells of the trophectoderm-derived extra-embryonic ectoderm in Eed(
      /-) embryos remain transcriptionally silent, despite lacking the PcG-mediated
      histone modifications that normally characterize the facultative heterochromatin
      of the inactive X-chromosome. Whereas undifferentiated Eed(-/-) trophoblast stem
      cells maintained XCI, reactivation of the inactive X-chromosome occurred when
      these cells were differentiated. These results indicate that PcG complexes are
      not necessary to maintain transcriptional silencing of the inactive X-chromosome
      in undifferentiated stem cells. Instead, PcG proteins seem to propagate cellular
      memory by preventing transcriptional activation of facultative heterochromatin
      during differentiation.

PMID- 16415859
TI  - Ever-fluctuating single enzyme molecules: Michaelis-Menten equation revisited.
AB  - Enzymes are biological catalysts vital to life processes and have attracted
      century-long investigation. The classic Michaelis-Menten mechanism provides a
      highly satisfactory description of catalytic activities for large ensembles of
      enzyme molecules. Here we tested the Michaelis-Menten equation at the single
      molecule level. We monitored long time traces of enzymatic turnovers for
      individual beta-galactosidase molecules by detecting one fluorescent product at a
      time. A molecular memory phenomenon arises at high substrate concentrations,
      characterized by clusters of turnover events separated by periods of low
      activity. Such memory lasts for decades of timescales ranging from milliseconds
      to seconds owing to the presence of interconverting conformers with broadly
      distributed lifetimes. We proved that the Michaelis-Menten equation still holds
      even for a fluctuating single enzyme, but bears a different microscopic
      interpretation.

PMID- 16415858
TI  - V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the
      protein degradative pathway.
AB  - The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal
      membranes is driven by V-ATPase-dependent intra-endosomal acidification. The
      molecular mechanism that mediates this pH-sensitive recruitment and its role are
      unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO
      with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes,
      interacts with ARNO in an intra-endosomal acidification-dependent manner, and
      disruption of this interaction results in reversible inhibition of endocytosis.
      Inhibition of endosomal acidification abrogates protein trafficking between early
      and late endosomal compartments. These data demonstrate the crucial role of early
      endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of
      the endocytic degradative pathway. They also indicate that V-ATPase could
      modulate membrane trafficking by recruiting and interacting with ARNO and Arf6;
      characteristics that are consistent with the role of V-ATPase as an essential
      component of the endosomal pH-sensing machinery.

PMID- 16415860
TI  - Dynamic polymorphism of single actin molecules in the actin filament.
AB  - Actin filament dynamics are critical in cell motility. The structure of actin
      filament changes spontaneously and can also be regulated by actin-binding
      proteins, allowing actin to readily function in response to external stimuli. The
      interaction with the motor protein myosin changes the dynamic nature of actin
      filaments. However, the molecular bases for the dynamic processes of actin
      filaments are not well understood. Here, we observed the dynamics of rabbit
      skeletal-muscle actin conformation by monitoring individual molecules in the
      actin filaments using single-molecule fluorescence resonance energy transfer
      (FRET) imaging with total internal reflection fluorescence microscopy (TIRFM).
      The time trajectories of FRET show that actin switches between low- and high-FRET
      efficiency states on a timescale of seconds. If actin filaments are chemically
      cross-linked, a state that inhibits myosin motility, the equilibrium shifts to
      the low-FRET conformation, whereas when the actin filament is interacting with
      myosin, the high-FRET conformation is favored. This dynamic equilibrium suggests
      that actin can switch between active and inactive conformations in response to
      external signals.

PMID- 16415861
TI  - Microarray-based method for monitoring yeast overexpression strains reveals small
      molecule targets in TOR pathway.
AB  - Identification of the cellular targets of small-molecule hits in phenotypic
      screens is a central challenge in the development of small molecules as
      biological tools and potential therapeutics. To facilitate the process of small
      molecule target identification, we developed a global, microarray-based method
      for monitoring the growth of pools of yeast strains, each overexpressing a
      different protein, in the presence of small molecules. Specifically, the growth
      of Saccharomyces cerevisiae strains harboring approximately 3,900 different
      overexpression plasmids was monitored in the presence of rapamycin, which
      inhibits the target of rapamycin (TOR) proteins. TOR was successfully identified
      as a candidate rapamycin target, and many additional gene products were
      implicated in the TOR signaling pathway. We also characterized the mechanism of
      LY-83583, a small-molecule suppressor of rapamycin-induced growth inhibition.
      These data enabled functional links to be drawn between groups of genes
      implicated in the TOR pathway, identified several candidate targets for LY-83583,
      and suggested a role for mitochondrial respiration in mediating rapamycin
      sensitivity.

PMID- 16415862
TI  - Alkylation of duplex DNA in nucleosome core particles by duocarmycin SA and
      yatakemycin.
AB  - (+)-Yatakemycin (1, Fig. 1) and (+)-duocarmycin SA (2) are exceptionally potent,
      naturally occurring antitumor agents that derive their biological properties
      through a characteristic sequence-selective DNA-alkylation reaction. Studies have
      shown that both the AT-rich binding selectivity (shape-selective recognition) and
      the alkylation catalysis (shape-dependent catalysis) that contribute to the
      alkylation selectivity are dependent on the DNA minor groove shape and size
      characteristics of an AT-rich sequence (ref. 6 and references therein; refs.
      7,8). Here we report the alkylation properties of yatakemycin and duocarmycin SA
      on free DNA (alpha-satellite DNA) and the same sequence bound in a nucleosome
      core particle (NCP) modeling the state of DNA in eukaryotic cells. Both compounds
      showed a clear, relatively unaltered ability to alkylate DNA packaged in NCPs in
      terms of both alkylating efficiency and sequence selectivity, despite the steric
      and conformational perturbations imposed by NCP packaging. These findings
      highlight the dynamic nature of NCP-bound DNA and illustrate that cell- and
      protein-free DNA-alkylation studies of members of this class of antitumor drugs
      provide valuable insights into their properties.

PMID- 16415863
TI  - Allosteric inhibitors of Bcr-abl-dependent cell proliferation.
AB  - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized
      at the molecular level by the expression of Bcr-abl, a 210-kDa fusion protein
      with deregulated tyrosine kinase activity. Encouraged by the clinical validation
      of Bcr-abl as the target for the treatment of CML by imatinib, we sought to
      identify pharmacological agents that could target this kinase by a distinct
      mechanism. We report the discovery of a new class of Bcr-abl inhibitors using an
      unbiased differential cytotoxicity screen of a combinatorial kinase-directed
      heterocycle library. Compounds in this class (exemplified by GNF-2) show
      exclusive antiproliferative activity toward Bcr-abl-transformed cells, with
      potencies similar to imatinib, while showing no inhibition of the kinase activity
      of full-length or catalytic domain of c-abl. We propose that this new class of
      compounds inhibits Bcr-abl kinase activity through an allosteric non-ATP
      competitive mechanism.

PMID- 16415864
TI  - An essential role for DeltaFosB in the nucleus accumbens in morphine action.
AB  - The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) and
      dorsal striatum by the repeated administration of drugs of abuse. Here, we
      investigated the role of DeltaFosB in the NAc in behavioral responses to opiates.
      We achieved overexpression of DeltaFosB by using a bitransgenic mouse line that
      inducibly expresses the protein in the NAc and dorsal striatum and by using viral
      mediated gene transfer to specifically express the protein in the NAc. DeltaFosB
      overexpression in the NAc increased the sensitivity of the mice to the rewarding
      effects of morphine and led to exacerbated physical dependence, but also reduced
      their sensitivity to the analgesic effects of morphine and led to faster
      development of analgesic tolerance. The opioid peptide dynorphin seemed to be one
      target through which DeltaFosB produced this behavioral phenotype. Together,
      these experiments demonstrated that DeltaFosB in the NAc, partly through the
      repression of dynorphin expression, mediates several major features of opiate
      addiction.

PMID- 16415865
TI  - Selective elimination of glutamatergic synapses on striatopallidal neurons in
      Parkinson disease models.
AB  - Parkinson disease is a common neurodegenerative disorder that leads to difficulty
      in effectively translating thought into action. Although it is known that
      dopaminergic neurons that innervate the striatum die in Parkinson disease, it is
      not clear how this loss leads to symptoms. Recent work has implicated
      striatopallidal medium spiny neurons (MSNs) in this process, but how and
      precisely why these neurons change is not clear. Using multiphoton imaging, we
      show that dopamine depletion leads to a rapid and profound loss of spines and
      glutamatergic synapses on striatopallidal MSNs but not on neighboring
      striatonigral MSNs. This loss of connectivity is triggered by a new mechanism
      dysregulation of intraspine Cav1.3 L-type Ca(2+) channels. The disconnection of
      striatopallidal neurons from motor command structures is likely to be a key step
      in the emergence of pathological activity that is responsible for symptoms in
      Parkinson disease.

PMID- 16415866
TI  - Role of p21-activated kinase pathway defects in the cognitive deficits of
      Alzheimer disease.
AB  - Defects in dendritic spines are common to several forms of cognitive deficits,
      including mental retardation and Alzheimer disease. Because mutation of p21
      activated kinase (PAK) can lead to mental retardation and because PAK-cofilin
      signaling is critical in dendritic spine morphogenesis and actin dynamics, we
      hypothesized that the PAK pathway is involved in synaptic and cognitive deficits
      in Alzheimer disease. Here, we show that PAK and its activity are markedly
      reduced in Alzheimer disease and that this is accompanied by reduced and
      redistributed phosphoPAK, prominent cofilin pathology and downstream loss of the
      spine actin-regulatory protein drebrin, which cofilin removes from actin. We
      found that beta-amyloid (Abeta) was directly involved in PAK signaling deficits
      and drebrin loss in Abeta oligomer-treated hippocampal neurons and in the Appswe
      transgenic mouse model bearing a double mutation leading to higher Abeta
      production. In addition, pharmacological PAK inhibition in adult mice was
      sufficient to cause similar cofilin pathology, drebrin loss and memory
      impairment, consistent with a potential causal role of PAK defects in cognitive
      deficits in Alzheimer disease.

PMID- 16415867
TI  - Immune cells contribute to the maintenance of neurogenesis and spatial learning
      abilities in adulthood.
AB  - Neurogenesis is known to take place in the adult brain. This work identifies T
      lymphocytes and microglia as being important to the maintenance of hippocampal
      neurogenesis and spatial learning abilities in adulthood. Hippocampal
      neurogenesis induced by an enriched environment was associated with the
      recruitment of T cells and the activation of microglia. In immune-deficient mice,
      hippocampal neurogenesis was markedly impaired and could not be enhanced by
      environmental enrichment, but was restored and boosted by T cells recognizing a
      specific CNS antigen. CNS-specific T cells were also found to be required for
      spatial learning and memory and for the expression of brain-derived neurotrophic
      factor in the dentate gyrus, implying that a common immune-associated mechanism
      underlies different aspects of hippocampal plasticity and cell renewal in the
      adult brain.

PMID- 16415868
TI  - Bidirectional behavioral plasticity of memory reconsolidation depends on
      amygdalar protein kinase A.
AB  - Reconsolidation-the stabilization of a memory after retrieval-is hypothesized to
      be a critical and distinct component of memory processing, the disruption of
      which results in memory impairment. In the rat, we found that activation of
      amygdalar protein kinase A (PKA) was sufficient to enhance memory only when it
      was retrieved; in contrast, PKA inhibition impaired reconsolidation. This study
      demonstrates both a selective enhancement and an impairment of memory
      reconsolidation dependent on amygdalar PKA.

PMID- 16415869
TI  - Serum response factor controls neuronal circuit assembly in the hippocampus.
AB  - Higher organisms rely on multiple modes of memory storage using the hippocampal
      network, which is built by precisely orchestrated mechanisms of axonal outgrowth,
      guidance and synaptic targeting. We demonstrate essential roles of the
      transcription factor serum response factor (SRF), a sensor of cytoskeletal actin
      dynamics, in all these processes. Conditional deletion of the mouse Srf gene
      reduced neurite outgrowth and abolished mossy fiber segregation, resulting in
      ectopic fiber growth inside the pyramidal layer. SRF-deficient mossy fibers
      aberrantly targeted CA3 somata for synapse formation. Axon guidance assays showed
      that SRF was a key mediator of ephrin-A and semaphorin guidance cues; in SRF
      deficient neurons, these resulted in the formation of F-actin-microtubule rings
      rather than complete growth cone collapse. Dominant-negative variants of the SRF
      cofactor megakaryocytic acute leukemia (MAL) severely impeded neurite outgrowth
      and guidance. These data highlight essential links between SRF-mediated
      transcription and axon guidance and circuit formation in the hippocampus.

PMID- 16415870
TI  - Molecular disruption of hypothalamic nutrient sensing induces obesity.
AB  - The sensing of circulating nutrients within the mediobasal hypothalamus may be
      critical for energy homeostasis. To induce a sustained impairment in hypothalamic
      nutrient sensing, adeno-associated viruses (AAV) expressing malonyl-coenzyme A
      decarboxylase (MCD; an enzyme involved in the degradation of malonyl coenzyme A)
      were injected bilaterally into the mediobasal hypothalamus of rats. MCD
      overexpression led to decreased abundance of long-chain fatty acyl-coenzyme A in
      the mediobasal hypothalamus and blunted the hypothalamic responses to increased
      lipid availability. The enhanced expression of MCD within this hypothalamic
      region induced a rapid increase in food intake and progressive weight gain.
      Obesity was sustained for at least 4 months and occurred despite increased plasma
      concentrations of leptin and insulin. These findings indicate that nutritional
      modulation of the hypothalamic abundance of malonyl-coenzyme A is required to
      restrain food intake and that a primary impairment in this central nutrient
      sensing pathway is sufficient to disrupt energy homeostasis and induce obesity.

PMID- 16415871
TI  - Systemic activation of dendritic cells by Toll-like receptor ligands or malaria
      infection impairs cross-presentation and antiviral immunity.
AB  - The mechanisms responsible for the immunosuppression associated with sepsis or
      some chronic blood infections remain poorly understood. Here we show that
      infection with a malaria parasite (Plasmodium berghei) or simple systemic
      exposure to bacterial or viral Toll-like receptor ligands inhibited cross
      priming. Reduced cross-priming was a consequence of downregulation of cross
      presentation by activated dendritic cells due to systemic activation that did not
      otherwise globally inhibit T cell proliferation. Although activated dendritic
      cells retained their capacity to present viral antigens via the endogenous major
      histocompatibility complex class I processing pathway, antiviral responses were
      greatly impaired in mice exposed to Toll-like receptor ligands. This is
      consistent with a key function for cross-presentation in antiviral immunity and
      helps explain the immunosuppressive effects of systemic infection. Moreover,
      inhibition of cross-presentation was overcome by injection of dendritic cells
      bearing antigen, which provides a new strategy for generating immunity during
      immunosuppressive blood infections.

PMID- 16415872
TI  - Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor
      signaling by mediating Mal degradation.
AB  - Toll-like receptor (TLR) signals that initiate innate immune responses to
      pathogens must be tightly regulated to prevent excessive inflammatory damage to
      the host. The adaptor protein Mal is specifically involved in signaling via TLR2
      and TLR4. We demonstrate here that after TLR2 and TLR4 stimulation Mal becomes
      phosphorylated by Bruton's tyrosine kinase (Btk) and then interacts with SOCS-1,
      which results in Mal polyubiquitination and subsequent degradation. Removal of
      SOCS-1 regulation potentiates Mal-dependent p65 phosphorylation and
      transactivation of NF-kappaB, leading to amplified inflammatory responses. These
      data identify a target of SOCS-1 that regulates TLR signaling via a mechanism
      distinct from an autocrine cytokine response. The transient activation of Mal and
      subsequent SOCS-1-mediated degradation is a rapid and selective means of limiting
      primary innate immune response.

PMID- 16415874
TI  - Achieving centimetre-scale supercollimation in a large-area two-dimensional
      photonic crystal.
AB  - Diffraction, a fundamental process in wave physics, leads to spreading of the
      optical beams as they propagate. However, new photonic crystal (PhC) meta
      materials can be nano-engineered to generate extreme anisotropy, resulting in
      apparent propagation of light without diffraction. This surprising phenomenon,
      called supercollimation, effectively freezes the spatial width of a light beam
      inside a PhC, observed over a few isotropic diffraction-lengths. However, using
      such experiments to predict the behaviour for longer propagation lengths is
      difficult, as a tiny error in a measured width can extrapolate to order unity
      uncertainty in the width at distances over hundreds of diffraction-lengths. Here,
      supercollimation is demonstrated in a macroscopic PhC system over centimetre
      scale distances, retaining spatial width confinement without the need for
      waveguides or nonlinearities. Through quantitative studies of the beam evolution
      in a two-dimensional PhC, we find that supercollimation possesses unexpected but
      inherent robustness with respect to short-scale disorder such as fabrication
      roughness, enabling supercollimation over 600 isotropic diffraction-lengths. The
      effects of disorder are identified through experiments and understood through
      rigorous simulations. In addition, a supercollimation steering capability is
      proposed.

PMID- 16415873
TI  - The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via
      Toll-like receptors 3, 7 and 9.
AB  - Here we have identified 'triple D' (3d), a recessive N-ethyl-N-nitrosourea
      induced mutation and phenotype in which no signaling occurs via the intracellular
      Toll-like receptors 3, 7 and 9 (sensors for double-stranded RNA, single-stranded
      RNA and unmethylated DNA, respectively). The 3d mutation also prevented cross
      presentation and diminished major histocompatibility complex class II
      presentation of exogenous antigen; it also caused hypersusceptibility to
      infection by mouse cytomegalovirus and other microbes. By positional
      identification, we found 3d to be a missense allele of Unc93b1, which encodes the
      12-membrane-spanning protein UNC-93B, a highly conserved molecule found in the
      endoplasmic reticulum with multiple paralogs in mammals. Innate responses to
      nucleic acids and exogenous antigen presentation, which both initiate in
      endosomes, thus seem to depend on an endoplasmic reticulum-resident protein,
      which suggests communication between these organellar systems.

PMID- 16415875
TI  - Electric-field-induced redistribution of polar nano-regions in a relaxor
      ferroelectric.
AB  - Relaxor ferroelectrics, with their strong dependence of polarization on the
      applied electric field, are of considerable technological importance. On a
      microscopic scale, however, there exists competition as well as coexistence
      between short-range and long-range polar order. The conventional picture is that
      the polar nano-regions (PNRs) that appear at high temperatures beyond the Curie
      transition, form nuclei for the field-induced long-range order at low
      temperatures. Here, we report high-energy X-ray diffuse-scattering measurements
      on the relaxor Pb(Zn(1/3)Nb(2/3))O(3) (PZN) to study the short-range polar order
      under an electric field applied along the [111] direction. In contrast to
      conventional expectations, the overall diffuse-scattering intensity is not
      suppressed. On the other hand, the field induces a marked change on the shape of
      the three-dimensional diffuse-scattering intensity pattern, corresponding to a
      redistribution of PNRs in real space. We show that these surprising results are
      consistent with a model in which the PNRs with [110]-type polarizations,
      orthogonal to that of the surrounding environment, are embedded and persist in
      the [111]-polarized ferroelectric order of the bulk.

PMID- 16415876
TI  - Chiral switching by spontaneous conformational change in adsorbed organic
      molecules.
AB  - Self-assembly of adsorbed organic molecules is a promising route towards
      functional surface nano-architectures, and our understanding of associated
      dynamic processes has been significantly advanced by several scanning tunnelling
      microscopy (STM) investigations. Intramolecular degrees of freedom are widely
      accepted to influence ordering of complex adsorbates, but although molecular
      conformation has been identified and even manipulated by STM, the detailed
      dynamics of spontaneous conformational change in adsorbed molecules has hitherto
      not been addressed. Molecular surface structures often show important
      stereochemical effects as, aside from truly chiral molecules, a large class of so
      called prochiral molecules become chiral once confined on a surface with an
      associated loss of symmetry. Here, we investigate a model system in which
      adsorbed molecules surprisingly switch between enantiomeric forms as they undergo
      thermally induced conformational changes. The associated kinetic parameters are
      quantified from time-resolved STM data whereas mechanistic insight is obtained
      from theoretical modelling. The chiral switching is demonstrated to enable an
      efficient channel towards formation of extended homochiral surface domains. Our
      results imply that appropriate prochiral molecules may be induced (for example,
      by seeding) to assume only one enantiomeric form in surface assemblies, which is
      of relevance for chiral amplification and asymmetric heterogenous catalysis.

PMID- 16415877
TI  - Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2
      dependent.
AB  - Control of inflammation is crucial to prevent damage to the host during
      infection. Lipoxins and aspirin-triggered lipoxins are crucial modulators of
      proinflammatory responses; however, their intracellular mechanisms have not been
      completely elucidated. We previously showed that lipoxin A4 (LXA4) controls
      migration of dendritic cells (DCs) and production of interleukin (IL)-12 in vivo.
      In the absence of LXA4 biosynthetic pathways, the resulting uncontrolled
      inflammation during infection is lethal, despite pathogen clearance. Here we show
      that lipoxins activate two receptors in DCs, AhR and LXAR, and that this
      activation triggers expression of suppressor of cytokine signaling (SOCS)-2. SOCS
      2-deficient DCs are hyper-responsive to microbial stimuli, as well as refractory
      to the inhibitory actions of LXA4, but not to IL-10. Upon infection with an
      intracellular pathogen, SOCS-2-deficient mice had uncontrolled production of
      proinflammatory cytokines, decreased microbial proliferation, aberrant leukocyte
      infiltration and elevated mortality. We also show that SOCS-2 is a crucial
      intracellular mediator of the anti-inflammatory actions of aspirin-induced
      lipoxins in vivo.

PMID- 16415878
TI  - Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in
      human renal transplants.
AB  - De novo lymphangiogenesis influences the course of different human diseases as
      diverse as chronic renal transplant rejection and tumor metastasis. The cellular
      mechanisms of lymphangiogenesis in human diseases are currently unknown, and
      could involve division of local preexisting endothelial cells or incorporation of
      circulating progenitors. We analyzed renal tissues of individuals with gender
      mismatched transplants who had transplant rejection and high rates of overall
      lymphatic endothelial proliferation as well as massive chronic inflammation.
      Donor-derived cells were detected by in situ hybridization of the Y chromosome.
      We compared these tissues with biopsies of essentially normal skin and intestine,
      and two rare carcinomas with low rates of lymphatic endothelial proliferation
      that were derived from individuals with gender-mismatched bone marrow
      transplants. Here, we provide evidence for the participation of recipient-derived
      lymphatic progenitor cells in renal transplants. In contrast, lymphatic vessels
      of normal tissues and those around post-transplant carcinomas did not incorporate
      donor-derived progenitors. This indicates a stepwise mechanism of inflammation
      associated de novo lymphangiogenesis, implying that potential lymphatic
      progenitor cells derive from the circulation, transmigrate through the connective
      tissue stroma, presumably in the form of macrophages, and finally incorporate
      into the growing lymphatic vessel.

PMID- 16415879
TI  - Reconstitution of chromatin transcription with purified components reveals a
      chromatin-specific repressive activity of p300.
AB  - Here we describe an in vitro chromatin transcription system in which chromatin
      assembly and transcription are carried out with purified and defined factors.
      With basal (also known as general) transcription factors and sequence-specific
      DNA-binding activators, we observed chromatin-specific, activation domain
      dependent transcription. We then examined the biochemical function of purified
      p300 in the absence of the endogenous factor and other related activities and
      found, unexpectedly, that p300 has a chromatin-specific, transcriptional
      repression activity that can be relieved by the addition of acetyl-CoA. This p300
      mediated repression is reversible, requires the p300 bromodomain but not the
      acetyltransferase region, and does not involve the formation of a stable,
      nuclease-resistant nucleoprotein complex. Hence, the mechanism of transcriptional
      repression by p300 is distinct from that of histone H1, PARP-1 or Sir2. These
      findings reveal a novel chromatin-specific repressive function of p300.

PMID- 16415880
TI  - Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in
      complex with RNA.
AB  - Bacterial tRNA adenosine deaminases (TadAs) catalyze the hydrolytic deamination
      of adenosine to inosine at the wobble position of tRNA(Arg2), a process that
      enables this single tRNA to recognize three different arginine codons in mRNA. In
      addition, inosine is also introduced at the wobble position of multiple
      eukaryotic tRNAs. The genes encoding these deaminases are essential in bacteria
      and yeast, demonstrating the importance of their biological activity. Here we
      report the crystallization and structure determination to 2.0 A of Staphylococcus
      aureus TadA bound to the anticodon stem-loop of tRNA(Arg2) bearing nebularine, a
      non-hydrolyzable adenosine analog, at the wobble position. The cocrystal
      structure reveals the basis for both sequence and structure specificity in the
      interactions of TadA with RNA, and it additionally provides insight into the
      active site architecture that promotes efficient hydrolytic deamination.

PMID- 16415881
TI  - Structural basis for the methylation site specificity of SET7/9.
AB  - Human SET7/9 is a protein lysine methyltransferase (PKMT) that methylates histone
      H3, the tumor suppressor p53 and the TBP-associated factor TAF10. To elucidate
      the determinants of its substrate specificity, we have solved the enzyme's
      structure bound to a TAF10 peptide and examined its ability to methylate histone
      H3, TAF10 and p53 substrates bearing either mutations or covalent modifications
      within their respective methylation sites. Collectively, our data reveal that
      SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and
      has a propensity to bind aspartates and asparagines on the C-terminal side of the
      lysine target. We then used a sequence-based approach with this motif to identify
      novel substrates for this PKMT. Among the putative targets is TAF7, which is
      methylated at Lys5 by the enzyme in vitro. These results demonstrate the
      predictive value of the consensus motif in identifying novel substrates for
      SET7/9.

PMID- 16415882
TI  - A global transcription cofactor bound to juxtaposed strands of unwound DNA.
AB  - The 1.74-A crystal structure of the human transcription cofactor PC4 in complex
      with a single-stranded 20-mer oligonucleotide reveals how symmetry-related beta
      surfaces of the protein homodimer interact with juxtaposed 5-nucleotide DNA
      regions running in opposite directions. The structure explains high-affinity
      binding of PC4 to the complementary strands of unwinding duplex DNA, and it
      suggests the cofactor may have a role in relaxing negative supercoils or exposing
      unpaired bases for sequence-specific recognition by other biomolecules.

PMID- 16415883
TI  - Structural definition of the F-actin-binding THATCH domain from HIP1R.
AB  - Huntingtin-interacting protein-1 related (HIP1R) has a crucial protein
      trafficking role, mediating associations between actin and clathrin-coated
      structures at the plasma membrane and trans-Golgi network. Here, we characterize
      the F-actin-binding region of HIP1R, termed the talin-HIP1/R/Sla2p actin
      tethering C-terminal homology (THATCH) domain. The 1.9-A crystal structure of the
      human HIP1R THATCH core reveals a large sequence-conserved surface patch created
      primarily by residues from the third and fourth helices of a unique five-helix
      bundle. Point mutations of seven contiguous patch residues produced significant
      decreases in F-actin binding. We also show that THATCH domains have a conserved C
      terminal latch capable of oligomerizing the core, thereby modulating F-actin
      engagement. Collectively, these results establish a framework for investigating
      the links between endocytosis and actin dynamics mediated by THATCH domain
      containing proteins.

PMID- 16415884
TI  - Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2
      diabetes.
AB  - We have previously reported suggestive linkage of type 2 diabetes mellitus to
      chromosome 10q. We genotyped 228 microsatellite markers in Icelandic individuals
      with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A
      microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2
      gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(
      9)). This was replicated in a Danish cohort (P = 4.8 x 10(-3)) and in a US cohort
      (P = 3.3 x 10(-9)). Compared with non-carriers, heterozygous and homozygous
      carriers of the at-risk alleles (38% and 7% of the population, respectively) have
      relative risks of 1.45 and 2.41. This corresponds to a population attributable
      risk of 21%. The TCF7L2 gene product is a high mobility group box-containing
      transcription factor previously implicated in blood glucose homeostasis. It is
      thought to act through regulation of proglucagon gene expression in
      enteroendocrine cells via the Wnt signaling pathway.

PMID- 16415885
TI  - Evolution of new protein topologies through multistep gene rearrangements.
AB  - New protein folds have emerged throughout evolution, but it remains unclear how a
      protein fold can evolve while maintaining its function, particularly when fold
      changes require several sequential gene rearrangements. Here, we explored
      hypothetical evolutionary pathways linking different topological families of the
      DNA-methyltransferase superfamily. These pathways entail successive gene
      rearrangements through a series of intermediates, all of which should be
      sufficiently active to maintain the organism's fitness. By means of directed
      evolution, and starting from HaeIII methyltransferase (M.HaeIII), we selected all
      the required intermediates along these paths (a duplicated fused gene and
      duplicates partially truncated at their 5' or 3' coding regions) that maintained
      function in vivo. These intermediates led to new functional genes that resembled
      natural methyltransferases from three known classes or that belonged to a new
      class first seen in our evolution experiments and subsequently identified in
      natural genomes. Our findings show that new protein topologies can evolve
      gradually through multistep gene rearrangements and provide new insights
      regarding these processes.

PMID- 16415886
TI  - MKS1, encoding a component of the flagellar apparatus basal body proteome, is
      mutated in Meckel syndrome.
AB  - Meckel syndrome (MKS) is a severe fetal developmental disorder reported in most
      populations. The clinical hallmarks are occipital meningoencephalocele, cystic
      kidney dysplasia, fibrotic changes of the liver and polydactyly. Here we report
      the identification of a gene, MKS1, mutated in MKS families linked to 17q. Mks1
      expression in mouse embryos, as determined by in situ hybridization, agrees well
      with the tissue phenotype of MKS. Comparative genomics and proteomics data
      implicate MKS1 in ciliary functions.

PMID- 16415888
TI  - Joint analysis is more efficient than replication-based analysis for two-stage
      genome-wide association studies.
AB  - Genome-wide association is a promising approach to identify common genetic
      variants that predispose to human disease. Because of the high cost of genotyping
      hundreds of thousands of markers on thousands of subjects, genome-wide
      association studies often follow a staged design in which a proportion
      (pi(samples)) of the available samples are genotyped on a large number of markers
      in stage 1, and a proportion (pi(samples)) of these markers are later followed up
      by genotyping them on the remaining samples in stage 2. The standard strategy for
      analyzing such two-stage data is to view stage 2 as a replication study and focus
      on findings that reach statistical significance when stage 2 data are considered
      alone. We demonstrate that the alternative strategy of jointly analyzing the data
      from both stages almost always results in increased power to detect genetic
      association, despite the need to use more stringent significance levels, even
      when effect sizes differ between the two stages. We recommend joint analysis for
      all two-stage genome-wide association studies, especially when a relatively large
      proportion of the samples are genotyped in stage 1 (pi(samples) >or= 0.30), and a
      relatively large proportion of markers are selected for follow-up in stage 2
      (pi(markers) >or= 0.01).

PMID- 16415887
TI  - The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome
      and the wpk rat.
AB  - Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder
      characterized by bilateral renal cystic dysplasia, developmental defects of the
      central nervous system (most commonly occipital encephalocele), hepatic ductal
      dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three
      loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We
      have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic
      to the Wpk locus in rat, which is a model with polycystic kidney disease,
      agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk
      gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic
      mutations for five MKS3-linked consanguineous families. MKS3 is a previously
      uncharacterized, evolutionarily conserved gene that is expressed at moderate
      levels in fetal brain, liver and kidney but has widespread, low levels of
      expression. It encodes a 995-amino acid seven-transmembrane receptor protein of
      unknown function that we have called meckelin.

PMID- 16415890
TI  - Long-term donor health and its relationship with outcome of allogeneic
      hematopoietic stem cell transplantation.
AB  - Data on long-term follow-up of donors for hematopoietic stem cell transplantation
      (HSCT) are limited. Donors of 612 adult allogeneic HSCT were studied, at a median
      of 81 (14-181) months post-HSC donation. Nine donors had severe health problems.
      Five donors died from aggressive malignancies or terminal illness, at a median of
      41 (16-57) months post-donation. Notably, all their recipients had leukemic
      relapses. In contrast, donors of recipients in remission were all living. This
      observation might be due to an inherent depressed immunosurveillance in the
      donors, or selection of donors with suboptimal health for desperate patients with
      poor risks pre-HSCT.

PMID- 16415891
TI  - Long-term remission in a patient with hepatosplenic gammadelta T cell lymphoma
      after cord blood stem cell transplantation following autologous peripheral blood
      stem cell transplantation.

PMID- 16415889
TI  - Physiogenomic resources for rat models of heart, lung and blood disorders.
AB  - Cardiovascular disorders are influenced by genetic and environmental factors. The
      TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray
      hybridizations, involving over 800 animals from 18 different rat strains. These
      strains comprise genetically diverse parental animals and a panel of chromosomal
      substitution strains derived by introgressing individual chromosomes from
      normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt
      sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in
      both genders, four tissues (heart, lung, liver, kidney) and two environmental
      conditions (normoxia, hypoxia). This translates into almost 400 high-quality
      direct comparisons (not including replicates) and over 100,000 pairwise
      comparisons. As each individual chromosomal substitution strain represents on
      average less than a 5% change from the parental genome, consomic strains provide
      a useful mechanism to dissect complex traits and identify causative genes. We
      performed a variety of data-mining manipulations on the profiles and used
      complementary physiological data from the PhysGen resource to demonstrate how
      TREX can be used by the cardiovascular community for hypothesis generation.

PMID- 16415892
TI  - Successful cord blood transplantation in a minor BCR-ABL+ CML patient who had
      been in lymphoid blast crisis at presentation.

PMID- 16415893
TI  - Autologous stem cell transplantation in elderly (>60 years) patients with non
      Hodgkin's lymphoma: a nation-wide analysis.
AB  - Limited experience is available on the feasibility and efficacy of autologous
      stem cell transplantation (ASCT) in elderly patients with non-Hodgkin's lymphoma
      (NHL). In 1994-2004 altogether 88 NHL patients > 60 years old received ASCT in
      six Finnish transplant centres. There were 57 male and 31 female patients with a
      median age of 63 years (range 60-70 years); 17 patients were>65 years. The
      histology included diffuse large B cell (n = 29), mantle cell (n = 27),
      follicular (n = 15), peripheral T cell (n = 12) and other (n = 5). Disease status
      at ASCT was I complete remission/partial remission (CR/PR) in 53 patients, II
      CR/PR in 30 patients and other in five patients. The conditioning regimens
      included BEAC (n = 49), BEAM (n = 34), TBI-CY (n = 4) and other (n = 1). Eighty
      four patients received PB grafts. The medians to reach neutrophils > 0.5 and
      platelets > 20 were 10 and 14 days, respectively. The early treatment-related
      mortality (TRM) (<100 days) was 11%. With a median follow-up of 21 months for all
      patients, 45 patients (51%) are alive. A relapse or progression after ASCT has
      been observed in 32 patients (36%). ASCT is feasible in selected elderly patients
      with NHL, but the early TRM seems to be higher than in younger patients.

PMID- 16415894
TI  - Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic
      transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism
      and survival.
AB  - Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled
      in a single-institution protocol for allogeneic transplantation with adjusted non
      myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and
      MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were
      unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg x 3 days), the
      subsequent 26 had Campath 30 mg x 3 days subcutaneously, and the final cohort of
      14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and
      risk factors. Campath-patients had no acute toxicity, fewer days with fever and
      antibiotics, and required fewer transfusions than ATG-treated patients. 3-d
      Campath patients showed lower lymphocyte counts from day +4, and CD4+, CD8+,
      CD19+ and NK cells recovered slower than in ATG-treated patients. More Campath
      patients developed mixed chimerism that required DLI. 3-d-Campath induced more
      serious and opportunistic infections than ATG, which resulted in a greater non
      relapse mortality and an impaired overall survival despite a low tumor-related
      mortality. The change of the Campath dosing schedule to one dose abrogated the
      deleterious effect of 3-d-Campath on immune recovery, severe infections and
      survival. Subcutaneous Campath is simple and provides strong immune suppression
      with no early toxicity, but dose limitation to 30 mg once is recommended.

PMID- 16415895
TI  - Prospective evaluation of procalcitonin in adults with non-neutropenic fever
      after allogeneic hematopoietic stem cell transplantation.
AB  - The aim of this study was to analyze whether procalcitonin (PCT) is a diagnostic
      marker of infectious diseases during the non-neutropenic period in patients who
      have received an allogeneic hematopoietic stem cell transplant (HSCT). We
      included 65 patients in whom an allogeneic HSCT was performed in a 2-year period
      (April 2002-July 2004). PCT levels were monitored in every febrile episode by an
      immunoluminometric assay. Febrile episodes were classified according to the final
      diagnosis in: fever of unknown origin, microbiologically or clinically documented
      infection and non-infectious fever. Fifty-two febrile episodes in the non
      neutropenic period were included in the study. Out of these 52, 26 had an
      infectious etiology: 11 fulfilled criteria for probable or proven invasive
      aspergillosis (IA), three were classified as possible invasive fungal infection
      (IFI) and 12 episodes were caused by other infections. Mean values of PCT on the
      first day of admission were: 8.0 (+/- 4.9) in probable-proven IA (P = 0.013,
      Kruskall-Wallis), 4.5 (+/- 3.4) in possible IFI and 1.5 (+/- 0.9) in infections
      other than IFI. Therefore, we could conclude that during the non-neutropenic
      phases of allogeneic HSCT, a high PCT value is associated significantly with IA.

PMID- 16415896
TI  - Catheter-related bacteremia due to Chryseobacterium indologenes in a bone marrow
      transplant recipient.

PMID- 16415897
TI  - Increased acute GvHD and higher transplant-related mortality in non-caucasians
      undergoing standard sibling allogeneic stem cell transplantation.
AB  - We conducted a retrospective study to compare outcome in Caucasians and non
      Caucasians undergoing standard sibling allogeneic SCT. End points of the study
      were to compare graft-versus-host disease (GvHD) occurrence and transplant
      related mortality (TRM). There were 251 patients, 43 non-Caucasian and 208
      Caucasian. A higher proportion of non-Caucasian patients developed acute GvHD
      (aGvHD) grade 2 or greater as compared to the Caucasian group (48 vs 26%,
      respectively) P = 0.02. With a median follow-up of 27 months, 26% (11/43) of non
      Caucasians and 14% (29/208) of Caucasian patients had died from TRM, which
      accounted for 55% of all deaths in the non-Caucasian group compared to 33% in
      Caucasians, P = 0.02. Overall survival 12 months post transplant was 64 vs 69% in
      the non-Caucasian and Caucasian groups, respectively (P = 0.43). Although there
      were higher numbers of CMV-positive patients in the non-Caucasian group, there
      were no deaths from CMV reactivation in this subgroup. We conclude that there is
      increased TRM and aGvHD following standard sibling allograft in the non-Caucasian
      population and this could be due to either differences in tumour biology or
      extrinsic factors such as socio-economic factors, nutritional status, post
      transplant care or presenting with late stage disease.

PMID- 16415898
TI  - Reduced-toxicity conditioning with treosulfan, fludarabine and ATG as preparative
      regimen for allogeneic stem cell transplantation (alloSCT) in elderly patients
      with secondary acute myeloid leukemia (sAML) or myelodysplastic syndrome (MDS).
AB  - We investigated a dose-reduced conditioning regimen consisting of treosulfan and
      fludarabine followed by allogeneic stem cell transplantation (SCT) in 26 patients
      with secondary AML or MDS. Twenty patients were transplanted from matched or
      mismatched unrelated donors and six from HLA-identical sibling donors. The median
      age of the patients was 60 years (range, 44-70). None of the patients was
      eligible for a standard myeloablative preparative regimen. No graft-failure was
      observed, and leukocyte and platelet engraftment were observed after a median of
      16 and 17 days, respectively. Acute graft-versus-host disease (GvHD) grade II-IV
      was seen in 23% and severe grade III GvHD in 12% of the patients. No patients
      experienced grade IV acute GvHD. Chronic GvHD was noted in 36% of the patients,
      which was extensive disease in 18%. The 2-year cumulative incidence of relapse
      was 21%. The relapse rate was higher in patients beyond CR1 or with intermediate
      two or high risk MDS (P = 0.02). The treatment-related mortality at day 100 was
      28%. The 2-year estimated overall and disease-free survival was 36-34%,
      respectively. No difference in survival was seen between unrelated and related
      SCT.

PMID- 16415899
TI  - Increased risk for treatment-related mortality after bone marrow transplantation
      in GSTM1-positive recipients.
AB  - Treatment-related mortality (TRM) is a major obstacle to successful allogeneic
      hematopoietic stem cell transplantation (HSCT). A variety of drugs are used in
      allogeneic HSCT, and a genetic polymorphism in metabolic enzymes could affect the
      metabolism of drugs and potentially influence TRM. Here, we focused attention on
      GSTM1 and GSTT1 enzymes, which metabolize chemotherapeutic agents, chemical
      carcinogens and by-products of oxidative stress and are absent from more than 50%
      of some populations. To assess the significance of homozygous GSTM1 and GSTT1
      gene deletion in HSCT, we analyzed DNA from 373 patients with hematological
      disease and their HLA-identical unrelated bone marrow donors using PCR.
      Homozygous GSTM1 and GSTT1 gene deletions were observed in 56 and 45% of
      patients, respectively, and 57 and 46% of donors, respectively. There was no
      significant association between GSTT1 polymorphism and any outcome. However, a
      GSTM1-positive genotype in recipients was significantly associated with higher
      TRM and lower survival. These results suggest that a GSTM1-null genotype in
      recipients protects against TRM after allogeneic HSCT. Further studies are needed
      to elucidate a mechanism of increased risk for TRM in GSTM1-positive recipients.

PMID- 16415900
TI  - Infections after allogeneic hematopoietic stem cell transplantation with a
      nonmyeloablative conditioning regimen.
AB  - Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning
      (NMSCT) may be associated with a reduced risk of infection compared to standard
      allogeneic HCT. We retrospectively analyzed incidence and risk factors of
      infection in 62 patients undergoing NMSCT with low-dose TBI +/- fludarabine and
      postgrafting CsA and MMF. The proportion of patients with any infection was 77%,
      but the majority of infectious events occurred beyond day 30. Donor other than
      sibling, older age, early disease and male gender were significant risk factors.
      The incidence of bacteremia was 55% at 1 year and the number of bacteremic
      episodes was 0.9 per patient (0.08 before day 30). The risk of bacteremia
      increased with older age and the use of a donor other than an HLA-identical
      sibling, but not with neutropenia. The incidence of infections other than
      bacteremia correlated with the use of corticosteroids. The risk of CMV infection
      increased with high-risk CMV serology, and risk of CMV disease with high-risk CMV
      serology, older age, first transplantation and a diagnosis of lymphoma. In
      conclusion, after NMSCT, infections are not frequent in the first 30 days post
      transplant but careful long-term monitoring is necessary thereafter.

PMID- 16415901
TI  - Reliability and validity of a patient self-administered daily questionnaire to
      assess impact of oral mucositis (OM) on pain and daily functioning in patients
      undergoing autologous hematopoietic stem cell transplantation (HSCT).
AB  - Oral mucositis (OM) is a frequent complication of myeloablative therapy and HSCT.
      We evaluated the feasibility, reliability, and validity of a new patient self
      reported daily questionnaire on OM and its impact on daily functions. This OM
      Daily Questionnaire (OMDQ), containing 10 items, was developed for use in
      palifermin clinical trials. In a phase 3 study, 212 patients received palifermin
      or placebo for three consecutive days before conditioning and three consecutive
      days after HSCT. Compliance rates were consistently >80% for most patients. Mouth
      and throat soreness (MTS) and MTS-Activity Limitations (MTS-AL) (swallowing,
      drinking, eating, talking, and sleeping) scores on consecutive days were highly
      correlated (days 7,8 = 0.70-0.86; test-retest reliability). Correlations among
      items measuring the same construct ranged between 0.5 and 0.8 (internal
      consistency reliability). The WHO Oral Toxicity scale was the clinical comparator
      to assess the criterion, discriminative, and evaluative validities of MTS-related
      questions. Most correlation coefficients between the WHO and MTS ranged between
      0.45 and 0.55. Patients with more severe WHO OM grades had higher MTS mean
      scores. Changes in MTS scores were similar, but patients detected changes 1-3
      days earlier than clinicians. In conclusion, the OMDQ is a feasible, reliable,
      valid, and responsive patient-reported measure of OM severity.

PMID- 16415902
TI  - The basic secretagogue compound 48/80 activates G proteins indirectly via
      stimulation of phospholipase D-lysophosphatidic acid receptor axis and 5-HT1A
      receptors in rat brain sections.
AB  - The basic secretagogues, such as compound 48/80 (c48/80) and mastoparans, are
      widely used histamine-releasing agents and their mechanism of action is commonly
      attributed to a direct, receptor-bypassing property to activate the G(i/o) class
      of G proteins. We tested here whether c48/80 could directly stimulate
      [(35)S]guanosine-5'-[gamma-thio]triphosphate ([(35)S]GTPgammaS) binding to rat
      brain sections in an attempt to visualize the entire signaling pool of G(i/o) in
      its native neuroanatomical context. Instead of direct G(i/o) activation, c48/80
      (100 microg ml(-1)) from various suppliers stimulated brain phospholipase D (PLD)
      activity, leading to the generation of endogenous phospholipids capable of
      activating brain white matter-enriched, G(i/o)-coupled lysophosphatidic acid
      (LPA) receptors. This response was sensitive to 1-butanol and was potently
      reversed by the LPA(1)/LPA(3) receptor-selective antagonist Ki16425 (IC(50) 59+/
      13 nM, mean+/-s.e.m.), and showed age-dependent decline, closely reflecting known
      developmental regulation of the PLD-LPA(1) receptor axis in the CNS. In addition,
      c48/80 was found to modestly activate hippocampal 5-HT(1A) receptors in a pH
      dependent and antagonist-sensitive manner. Consistent with the lack of direct
      G(i/o)-activating properties in brain sections, c48/80 showed no activity in
      classical membrane [(35)S]GTPgammaS binding assays. Instead, c48/80 from one
      particular manufacturer elicited non-specific effect in these assays, therefore
      challenging the previous interpretations regarding the compound's ability to
      activate G proteins directly. We conclude that c48/80 is not a receptor-bypassing
      general G protein activator but rather activates PLD, leading to generation of
      endogenous LPA receptor-activating phospholipids. This property may also
      contribute to the compound's ability to release histamine from mast cells.

PMID- 16415903
TI  - Differential activation of G-proteins by mu-opioid receptor agonists.
AB  - We investigated the ability of the activated mu-opioid receptor (MOR) to
      differentiate between myristoylated G(alphai1) and G(alphaoA) type G(alpha)
      proteins, and the maximal activity of a range of synthetic and endogenous
      agonists to activate each G(alpha) protein. Membranes from HEK293 cells stably
      expressing transfected MOR were chaotrope extracted to denature endogenous G
      proteins and reconstituted with specific purified G-proteins. The G(alpha)
      subunits were generated in bacteria and were demonstrated to be recognised
      equivalently to bovine brain purified G(alpha) protein by CB(1) cannabinoid
      receptors. The ability of agonists to catalyse the MOR-dependent
      GDP/[(35)S]GTP(gamma)S exchange was then compared for G(alphai1) and G(alphaoA).
      Activation of MOR by DAMGO produced a high-affinity saturable interaction for
      G(alphaoA) (K(m)=20+/-1 nM) but a low-affinity interaction with G(alphai1)
      (K(m)=116+/-12 nM). DAMGO, met-enkephalin and leucine-enkephalin displayed
      maximal G(alpha) activation among the agonists evaluated. Endomorphins 1 and 2,
      methadone and beta-endorphin activated both G(alpha) to more than 75% of the
      maximal response, whereas fentanyl partially activated both G-proteins.
      Buprenorphine and morphine demonstrated a statistically significant difference
      between the maximal activities between G(alphai1) and G(alphaoA). Interestingly,
      DAMGO, morphine, endomorphins 1 and 2, displayed significant differences in the
      potencies for the activation of the two G(alpha). Differences in maximal activity
      and potency, for G(alphai1) versus G(alphaoA), are both indicative of agonist
      selective activation of G-proteins in response to MOR activation. These findings
      may provide a starting point for the design of drugs that demonstrate greater
      selectivity between these two G-proteins and therefore produce a more limited
      range of effects.

PMID- 16415904
TI  - Angiotensin II acutely decreases myocardial stiffness: a novel AT1, PKC and
      Na+/H+ exchanger-mediated effect.
AB  - Acute effects of angiotensin II (AngII) on diastolic properties of the myocardium
      were investigated. Increasing concentrations of AngII (10(-9) to 10(-5) M) were
      added to rabbit papillary muscles in the absence (n=11) or presence of: (i) AT1
      receptor antagonists, losartan (10(-6) M; n=7) or ZD-7155 (10(-7) M; n=8); (ii)
      ZD-7155 (10(-7) M) plus AT2 receptor antagonist PD-123,319 (2 x 10(-6) M; n=6);
      (iii) PKC inhibitor, chelerythrine (10(-5) M; n=8); or (iv) Na(+)/H(+) exchanger
      (NHE) inhibitor, 5-(N-methyl-N-isobutyl)-amiloride (10(-6) M; n=10). Passive
      length-tension relations were constructed before and after a single concentration
      of AngII (10(-5) M, n=6). Effects of AngII infusion (10 microg kg(-1) min(-1))
      were evaluated in in situ rabbit hearts. AngII concentration dependently
      increased inotropy and resting muscle length (RL). At 10(-5) M, active tension
      increased 43.3+/-6.25% and RL 1.96+/-0.4%. Correcting RL to its initial value
      resulted in a 46+/-4% decrease of resting tension, indicating decreased muscle
      stiffness, as confirmed by the right and downward shift of the passive length
      tension relation promoted by AngII. In the intact heart, at matched systolic
      pressures of 112 mmHg, AngII decreased end-diastolic pressures from 10.3+/-0.3 to
      5.9+/-0.5 mmHg, and minimal diastolic pressures from 8.4+/-0.5 to 4.6+/-0.6 mmHg.
      AT1 blockade inhibited AngII effects on myocardial inotropy and stiffness, while
      PKC or NHE inhibition only significantly attenuated its effects on resting length
      and tension. In conclusion, AngII decreases myocardial stiffness, an effect that
      requires AT1 receptor activation and is mediated by PKC and NHE. This represents
      a novel mechanism of acute neurohumoral modulation of diastolic function,
      suggesting that AngII is a powerful regulator of cardiac filling.

PMID- 16415905
TI  - A3 adenosine receptor antagonists delay irreversible synaptic failure caused by
      oxygen and glucose deprivation in the rat CA1 hippocampus in vitro.
AB  - The role of adenosine A3 receptor activation during ischaemia-like conditions
      produced by oxygen and glucose deprivation (OGD) was evaluated with extracellular
      recordings from the CA1 region of rat hippocampal slices. In all, 7 min of OGD
      evoked tissue anoxic depolarisation (AD, peak at approximately 7 min from OGD
      start, n=20) and were invariably followed by irreversible loss of electrically
      evoked field epsps (fepsps, n=42).The selective adenosine A3 antagonists 3-propyl
      6-ethyl-5[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523,
      1-100 nM, n=31), N-[9-chloro-2-(2-furanyl)[1,2,4]-triazolo[1,5-c]quinazolin-5
      yl]benzeneacetamide (MRS 1220, 100 nM, n=7), N-(2-methoxyphenyl)-N'-[2-(3
      pyrindinyl)-4-quinazolinyl]-urea, (VUF 5574, 100 nM, n=3) and 5-[[(4
      pyridyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,3-e]1,2,4
      triazolo[1,5-c]pyrimidine hydrochloride (1 nM, n=4), prevented the irreversible
      failure of neurotransmission induced by 7 min OGD (n=45) and the development of
      AD in 20 out of 22 monitored slices. When tested on OGD episodes of longer
      duration (8-10 min, n=18), 100 nM MRS 1523 prevented or delayed the appearance of
      AD and exerted a protective effect on neurotransmission for episodes of up to 9
      min duration. In the absence of AD, the fepsp recovery was almost total,
      regardless of OGD episode duration. These findings support the notion that A3
      receptor stimulation is deleterious during ischaemia and suggest that selective
      A3 receptor block may substantially increase the resistance of the CA1
      hippocampal region to ischaemic damage.

PMID- 16415906
TI  - A role for voltage-gated, but not Ca2+-activated, K+ channels in regulating
      spontaneous contractile activity in myometrium from virgin and pregnant rats.
AB  - The roles of voltage-gated (K(V)) and large conductance Ca2+-activated K+
      (BK(Ca)) channels in regulating basal contractility in myometrial smooth muscle
      are unresolved. The aim of this study was to determine the effects of inhibition
      of these channels on spontaneous rhythmic contraction in myometrial strips from
      four groups of rats: nonpregnant and during early (day 7), mid- (day 14), and
      late (day 21) pregnancy. BK(Ca) channels were inhibited using iberiotoxin (1-100
      nM), paxilline (1-10 microM) or penitrem A (1-500, or 3000 nM); K(V) channels
      were inhibited using tetraethylammonium (TEA; 1-10 mM) and/or 4-aminopyridine (4
      AP; 1-5 mM). Contractility was assessed as mean integral tension (MIT).
      Time/vehicle controls were also performed. None of the selective BK(Ca) channel
      inhibitors significantly affected contractility in myometrial strips from either
      nonpregnant or pregnant animals. 4-AP caused concentration-dependent increases in
      MIT in myometrium in all four groups. TEA (5 and 10 mM) significantly increased
      MIT in myometrium from nonpregnant, and mid- and late pregnant rats, but not in
      myometrium from early pregnant rats. TEA and 4-AP still caused an increase in MIT
      following treatment with 3000 nM penitrem A or a combination of propranolol,
      phentolamine, atropine (all 1 microM) and capsaicin (10 microM) in myometrial
      strips from nonpregnant rats. These results indicate that whereas BK(Ca) channels
      play little or no part in controlling basal rhythmicity in rat myometrium, K(V)
      channels appear to play a crucial role in this regard, especially during mid- and
      late pregnancy.

PMID- 16415907
TI  - Vasorelaxant effects of oleamide in rat small mesenteric artery indicate action
      at a novel cannabinoid receptor.
AB  - Oleamide (cis-9-octadecenoamide) exhibits some cannabimimetic responses despite
      its low affinities at the currently known cannabinoid receptors. Here we have
      investigated whether or not it is a vasorelaxant in rat small mesenteric
      arteries. Oleamide elicited vasorelaxation (EC50=1.2+/-0.2 microM, Rmax=99.1+/
      3.9%, n=8) which was reduced by endothelial removal. Nitric oxide synthase
      inhibition reduced the response (EC50=5.3+/-1.6 microM, Rmax=59.2+/-7.7%, n=7;
      P<0.01) as did blockade of Ca2+-sensitive K+ channels (KCa) with apamin plus
      charybdotoxin (both 50 nM) (EC50=2.1+/-0.2 microM, Rmax=58.4+/-1.9%, n=5;
      P<0.05). Desensitisation of vanilloid receptors with capsaicin (10 microM for 30
      min) shifted the oleamide concentration-response curve approximately 30-fold to
      the right (n=7; P<0.01). Pertussis toxin (400 ng ml-1 for 2 h) caused a two-fold
      shift in the response curve (EC50=2.2+/-0.4 microM, Rmax=66.8+/-4.5%, n=6;
      P<0.01). Rimonabant (CB1 cannabinoid receptor antagonist; SR141716A; 3 microM)
      significantly inhibited relaxation induced by oleamide (EC50=3.5+/-0.3 microM,
      Rmax=75.1+/-1.9%; n=8; P<0.05). In contrast, neither the more selective CB1
      receptor antagonist, AM251 (1 microM), nor the CB2 antagonist, SR144528 (1
      microM), had significant effects. O-1918 (10 microM), a putative antagonist at a
      novel endothelial cannabinoid receptor (abnormal-cannabidiol site), markedly
      reduced the relaxation to oleamide (n=7; P<0.01). It is concluded that oleamide
      responses in the rat isolated small mesenteric artery are partly dependent on the
      presence of the endothelium, activation of Ca2+-sensitive K+ channels (KC)) and
      involve capsaicin-sensitive sensory nerves. Oleamide may share a receptor
      (sensitive to rimonabant and O-1918, and coupled to KC) and Gi/o) with anandamide
      in this vessel. This might be distinct from both of the known cannabinoid
      receptors and the novel abnormal-cannabidiol site.

PMID- 16415908
TI  - Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2
      deficient mice.
AB  - Based on pharmacological criteria, we previously suggested that in the mouse
      aorta, endothelium-dependent relaxation by nucleotides is mediated by P2Y1
      (adenosine diphosphate (ADP)), P2Y2 (adenosine triphosphate (ATP)) and P2Y6
      (uridine diphosphate (UDP)) receptors. For UTP, it was unclear whether P2Y2, P2Y6
      or yet another subtype was involved. Therefore, in view of the lack of selective
      purinergic agonists and antagonists, we used P2Y2-deficient mice to clarify the
      action of UTP. Thoracic aorta segments (width 2 mm) of P2Y2-deficient and wild
      type (WT) mice were mounted in organ baths to measure isometric force development
      and intracellular calcium signalling. Relaxations evoked by ADP, UDP and
      acetylcholine were identical in knockout and WT mice, indicating that the
      receptors for these agonists function normally. P2Y2-deficient mice showed
      impaired ATP- and adenosine 5'[gamma-thio] triphosphate (ATPgammaS)-evoked
      relaxation, suggesting that in WT mice, ATP and ATPgammaS activate predominantly
      the P2Y2 subtype. The ATP/ATPgammaS-evoked relaxation and calcium signals in the
      knockout mice were partially rescued by P2Y1, as they were sensitive to 2'-deoxy
      N6-methyladenosine 3',5'-bisphosphate (MRS2179), a P2Y1-selective antagonist. In
      contrast to ATP, the UTP-evoked relaxation was not different between knockout and
      WT mice. Moreover, the action of UTP was not sensitive to MRS2179. Therefore, the
      action of UTP is probably mediated mainly by a P2Y6(like) receptor subtype. In
      conclusion, we demonstrated that ATP-evoked relaxation of the murine aorta is
      mainly mediated by P2Y2. But this P2Y2 receptor has apparently no major role in
      UTP-evoked relaxation. The vasodilator effect of UTP is probably mediated mainly
      by a P2Y6(like) receptor.

PMID- 16415909
TI  - Effects of haloperidol and clozapine on sensorimotor gating deficits induced by 5
      hydroxytryptamine depletion in the brain.
AB  - Evidence is increasing for a role of brain 5-hydroxytryptamine (5-HT) systems in
      schizophrenia. We previously showed that brain 5-HT depletion causes disruption
      of prepulse inhibition, a measure of sensorimotor gating that is deficient in
      schizophrenia. Antipsychotic treatment has been reported to reverse these
      deficits in patients with schizophrenia. The present study was designed to
      investigate the ability of antipsychotic drugs to reverse prepulse inhibition
      deficits caused by lesions of the brain 5-HT system in rats. In male Sprague
      Dawley rats, selected parts of the brain 5-HT systems were lesioned by micro
      injection of the 5-HT neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe
      nucleus (DRN) or median raphe nucleus (MRN). The effects of antipsychotic drugs
      on lesion-induced changes in prepulse inhibition were examined 2 weeks after the
      surgery. There was significant disruption of prepulse inhibition in the MRN
      lesioned group compared to sham-operated controls. This deficiency in prepulse
      inhibition was restored by clozapine (1 and 5 mg kg(-1)) treatment, and by
      treatment with a relatively high dose of haloperidol (0.25 mg kg(-1)). There was
      no significant effect of the DRN lesions on prepulse inhibition compared with
      sham-operated controls. These results indicate that 5-HT depletion in MRN
      innervated brain structures leads to disruption of prepulse inhibition. Treatment
      with both antipsychotic drugs, haloperidol and clozapine, significantly increased
      prepulse inhibition in these animals back to the level seen in sham-operated
      controls. The present findings highlight the importance of the 5-HT systems in
      cognitive models of schizophrenia.

PMID- 16415910
TI  - Activation of insulin-like growth factor I receptor-mediated pathway by
      ginsenoside Rg1.
AB  - Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a
      novel class of potent phytoestrogen. The present study aims at investigating the
      molecular mechanisms involved in mediating its actions in human breast cancer
      (MCF-7) cells. Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen
      responsive pS2 mRNA expression (P<0.05) without alteration of estrogen receptor
      alpha (ERalpha) protein or mRNA expression in MCF-7 cells. In addition, 10(-14)
      10(-4) M of Rg1 does not demonstrate specific binding to ERalpha. We hypothesize
      that Rg1 may exert its actions in MCF-7 cell via the activation of crosstalk
      between ER- and insulin growth factor I receptor (IGF-IR)-dependent pathways. The
      results indicate that Rg1 significantly increases IGF-IR expression and IGF-IR
      promoter activity in MCF-7 cells (P<0.05). Cotreatment of MCF-7 cells with 1 muM
      of estrogen antagonist ICI 182,780 completely abolishes the effects of Rg1 on IGF
      IR expression.Furthermore, Rg1 enhances tyrosine phosphorylation of IRS-1 in MCF
      7 cells upon IGF-I stimulation and the activation of IRS-1 phosphorylation is
      also ER-dependent. Taken together, our results suggest that Rg1 not only
      increases IGF-IR expression but also enhances IGF-IR-mediated signaling pathways
      in MCF-7 cells. The stimulation of IGF-IR expression by Rg1 in MCF-7 cells
      appears to require ER, and its actions might involve ligand-independent
      activation of ER.

PMID- 16415911
TI  - Depletion of intracellular Ca2+ stores enhances flow-induced vascular dilatation
      in rat small mesenteric artery.
AB  - The effect of depleting intracellular Ca2+ stores on flow-induced vascular
      dilatation and the mechanism responsible for the vasodilatation were examined in
      rat isolated small mesenteric arteries. The arteries were pressurized to 50 mmHg
      and preconstricted with phenylephrine. Intraluminal flow reversed the effect of
      phenylephrine, resulting in vasodilatation. Flow dilatation consisted of an
      initial transient peak followed by a sustained plateau phase. The magnitude of
      dilatation was markedly reduced by removing Ca2+ from the intraluminal flow
      medium. Depletion of intracellular Ca2+ stores with either cyclopiazonic acid
      (CPA, 2 microM) or 1,4-dihydroxy-2,5-di-tert-butylbenzene (BHQ, 10 microM)
      significantly augmented the magnitude of flow dilatation. Flow-induced
      endothelial cell Ca2+ influx was also markedly enhanced in arteries pretreated
      with CPA or BHQ.Flow-induced dilatation was insensitive to Nw-nitro-L-arginine
      methyl ester (100 microM) plus indomethacin (3 microM) or to oxyhemoglobin (3
      microM), but was markedly reduced by 30 mM extracellular K+ or 2 mM
      tetrabutylammonium (TBA), suggesting an involvement of EDHF. Catalase at 1200 U
      ml-1 abolished the flow-induced dilatation, while the application of exogenous
      H2O2 (90-220 microM) induced relaxation in phenylephrine-preconstricted arteries.
      Relaxation to exogenous H2O2 was blocked in the presence of 30 mM extracellular
      K+, and H2O2 (90 microM) hyperpolarized the smooth muscle cells, indicating that
      H2O2 can act as an EDHF. In conclusion, flow-induced dilatation in rat mesenteric
      arteries can be markedly enhanced by prior depletion of intracellular Ca2+
      stores. Furthermore, these data are consistent with a role for H2O2 as the
      vasodilator involved.

PMID- 16415912
TI  - Actions of flecainide on susceptibility to phase-2 ventricular arrhythmias during
      infarct evolution in rat isolated perfused hearts.
AB  - The mechanism of flecainide-induced unexpected death remains uncertain. Phase-2
      ventricular arrhythmias occur during infarct evolution. We examined whether
      flecainide (0.74 and 1.48 microM, representing the peak unbound plasma and total
      blood concentrations, respectively, at 'therapeutic' dosage) has proarrhythmic
      activity on phase-2 arrhythmia susceptibility during infarct evolution. To
      achieve this, we used the Langendorff-perfused rat heart preparation (n=8 per
      group) in which baseline phase-2 arrhythmia susceptibility is low. Left main
      coronary occlusion evoked phase-1 (acute ischaemia-induced) ventricular
      arrhythmias including fibrillation (VF) in all hearts. By 90 min, hearts were
      relatively arrhythmia-free. Randomized and blinded switch of perfusion to
      flecainide at 90 min caused no increase over baseline in the incidence of VF,
      tachycardia (VT) or premature beats (VPB) during the following 150 min of
      ischaemia, or during reperfusion (begun 240 min after the onset of ischaemia). In
      separate hearts, catecholamines (313 nM norepinephrine and 75 nM epinephrine)
      were co-perfused with flecainide from 90 min of ischaemia. Catecholamine
      perfusion increased heart rate, coronary flow and QT interval, and shortened PR
      interval (all P<0.05), actions that were not altered by flecainide. Catecholamine
      perfusion caused a weak nonsignificant increase in phase-2 VPB, VT and VF
      incidence, but there was no proarrhythmic interaction with flecainide. In
      conclusion, the present findings suggest that the increased risk of death
      associated with clinical use of flecainide is not due to facilitation of phase-2
      ventricular arrhythmias.

PMID- 16415913
TI  - The antiarrhythmic peptide rotigaptide (ZP123) increases gap junction
      intercellular communication in cardiac myocytes and HeLa cells expressing
      connexin 43.
AB  - We investigated the effects of rotigaptide (ZP123), a stable hexapeptide with
      antiarrhythmic properties, on gap junction mediated intercellular communication
      in contracting rat neonatal cardiac myocytes, HL-1 cells derived from cardiac
      atrium and in HeLa cells transfected with cDNA encoding Cx43-GFP, Cx32-GFP, Cx26
      GFP, wild-type Cx43 or wild-type Cx26. Intercellular communication was monitored
      before and after treatment with rotigaptide following microinjection of small
      fluorescent dyes (MW<1 kDa). The communication-modifying effect of rotigaptide
      was confined to cells expressing Cx43 since the peptide had no effect on dye
      transfer in HeLa cells expressing Cx32-GFP, Cx26-GFP or wild-type Cx26. In
      contrast, HeLa cells expressing Cx43-GFP exposed to 50 nM rotigaptide for 5 h
      showed a 40% increase in gap junction mediated communication. Rotigaptide (50 nM)
      increased intercellular dye transfer in myocytes and atrial HL-1 cells, where
      Cx43 is the dominant connexin. However, it caused no change in cell beating rates
      of cardiac myocytes. Western blot analysis showed that rotigaptide did not modify
      the overall level of Cx43 expression and changes in the phosphorylation status of
      the protein were not observed.We conclude that the effects of rotigaptide were
      confined to cells expressing Cx43.

PMID- 16415915
TI  - Neural stem cell proliferation is decreased in schizophrenia, but not in
      depression.
AB  - The phenomenon of adult neurogenesis (AN), that is, the generation of functional
      neurons from neural stem cells in the dentate gyrus of the hippocampus, has
      attracted remarkable attention, especially as it was shown that this process is
      also active in the human brain. Based on animal studies, it has been suggested
      that reduced AN is implicated in the etiopathology of psychiatric disorders, and
      that stimulation of AN contributes to the mechanism of action of antidepressant
      therapies. As data from human post-mortem brain are still lacking, we
      investigated whether the first step of AN, that is, the level of neural stem cell
      proliferation (NSP; as quantified by Ki-67 immunohistochemistry), is altered in
      tissue from the Stanley Foundation Neuropathology Consortium comprising brain
      specimens from patients with bipolar affective disorder, major depression,
      schizophrenia as well as control subjects (n=15 in each group). The hypothesis
      was that stem cell proliferation is reduced in affective disorders, and that
      antidepressant treatment increases NSP. Neither age, brain weight or pH, brain
      hemisphere investigated nor duration of storage had an effect on NSP. Only in
      bipolar disorder, post-mortem interval was a significant intervening variable. In
      disease, onset of the disorder and its duration likewise did not affect NSP.
      Also, cumulative lifetime dose of fluphenazine was not correlated with NSP, and
      presence of antidepressant treatment did not result in an increase of NSP.
      Concerning the different diagnostic entities, reduced amounts of newly formed
      cells were found in schizophrenia, but not in major depression. Our findings
      suggest that reduced NSP may contribute to the pathogenesis of schizophrenia,
      whereas the rate of NSP does not seem to be critical to the etiopathology of
      affective disorders, nor is it modified by antidepressant drug treatment.

PMID- 16415916
TI  - Pharmacovigilance in a genomic era.

PMID- 16415914
TI  - Multiple signalling pathways involved in beta2-adrenoceptor-mediated glucose
      uptake in rat skeletal muscle cells.
AB  - 1. Beta-adrenoceptor (AR) agonists increase 2-deoxy-[3H]-D-glucose uptake (GU)
      via beta2-AR in rat L6 cells. The beta-AR agonists, zinterol (beta2-AR) and (-)
      isoprenaline, increased cAMP accumulation in a concentration-dependent manner
      (pEC50=9.1+/-0.02 and 7.8+/-0.02). Cholera toxin (% max increase 141.8+/-2.5) and
      the cAMP analogues, 8-bromo-cAMP (8Br-cAMP) and dibutyryl cAMP (dbcAMP), also
      increased GU (196.8+/-13.5 and 196.4+/-17.3%). 2. The adenylate cyclase
      inhibitor, 2',5'-dideoxyadenosine (50 microM), significantly reduced cAMP
      accumulation to zinterol (100 nM) (109.7+35.0 to 21.6+4.5 pmol well(-1)), or
      forskolin (10 microM) (230.1+/-58.0 to 107.2+/-26.3 pmol well(-1)), and partially
      inhibited zinterol-stimulated GU (217+/-26.3 to 176.1+/-20.4%). The protein
      kinase A (PKA) inhibitor, 4-cyano-3-methylisoquinoline (100 nM), did not inhibit
      zinterol-stimulated GU. The PDE4 inhibitor, rolipram (10 microM), increased cAMP
      accumulation to zinterol or forskolin, and sensitised the GU response to
      zinterol, indicating a stimulatory role of cAMP in GU. 3. cAMP accumulation
      studies indicated that the beta2-AR was desensitised by prolonged stimulation
      with zinterol, but not forskolin, whereas GU responses to zinterol increased with
      time, suggesting that receptor desensitisation may be involved in GU. Receptor
      desensitisation was not reversed by inhibition of PKA or Gi. 4. PTX pretreatment
      (100 ng ml(-1)) inhibited insulin or zinterol-stimulated but not 8Br-cAMP or
      dbcAMP-stimulated GU. The PI3K inhibitor, LY294002 (1 microM), inhibited insulin-
      (174.9+/-5.9 to 142.7+/-2.7%) and zinterol- (166.9+/-7.6 to 141.1+/-8.1%) but not
      8 Br-cAMP-stimulated GU. In contrast to insulin, zinterol did not cause
      phosphorylation of Akt. 5. The results suggest that GU in L6 cells involves three
      mechanisms: (1) an insulin-dependent pathway involving PI3K, (2) a beta2-AR
      mediated pathway involving both cAMP and PI3K, and (3) a receptor-independent
      pathway suggested by cAMP analogues that increase GU independently of PI3K. PKA
      appears to negatively regulate beta2-AR-mediated GU.

PMID- 16415917
TI  - Topiramate stimulates glucose transport through AMP-activated protein kinase
      mediated pathway in L6 skeletal muscle cells.
AB  - The use of topiramate (TPM) in the treatment of binge-eating disorder, bulimia
      nervosa, and antipsychotic-induced weight gain has recently increased, however,
      the exact molecular basis for its effects on body weight reduction and improved
      glucose homeostasis, is yet to be elucidated. Here we investigated the effect and
      signaling pathway of TPM on glucose uptake in L6 rat skeletal muscle cells, which
      account for >70% of glucose disposal in the body. Intriguingly, we found that TPM
      (10 microM) stimulated the rate of glucose uptake up to twofold increase. And TPM
      stimulated glucose transport was inhibited with the overexpression of dominant
      negative form of AMP-activated protein kinase (AMPK), an important mediator in
      glucose transport, implicating that AMPK-mediated pathway is involved. The TPM
      stimulated glucose transport was blocked by SB203580, a specific inhibitor of
      AMPK downstream mediator, p38 mitogen-activated protein kinase (MAPK) protein.
      LY294002, an inhibitor of phosphatidylinositol (PI) 3-kinase, which is another
      crucial mediator in independent glucose transport pathway, did not inhibit TPM
      stimulated glucose transport. We also found that TPM increased the
      phosphorylation level of AMPK and p38 MAPK, whereas no effect on the activity of
      PI 3-kinase of TPM, when assessed by PI 3-kinase assay, was observed. These
      results together suggest that TPM stimulates glucose transport, not via PI 3
      kinase mediated, but via AMPK-mediated pathway in skeletal muscle cells, thereby
      contributing to the body weight regulation and glucose homeostasis.

PMID- 16415918
TI  - Pharmacogenomics and regulatory decision making: an international perspective.

PMID- 16415919
TI  - Relevance of frequent mu-opioid receptor polymorphisms for opioid activity in
      healthy volunteers.
AB  - Polymorphisms in the mu-opioid receptor gene (OPRM1) are primary candidate
      sources of clinical variability in opioid therapy. Apart from the 118A>G single
      nucleotide polymorphism, nothing is known about the role of OPRM1 mutations in
      opioid therapy. The influence of the OPRM1 mutations on opioid pharmacodynamics
      was assessed in pooled data from 31 healthy volunteers obtained in previous
      studies with available plasma concentrations and pupil diameters after
      intravenous administration of morphine or morphine-6-glucuronide (M6G). A total
      of 24 candidate ORPM1 mutations were screened for and those found at an allelic
      frequency of at least 5% in the 31 subjects were analyzed for functional
      consequences, using population pharmacokinetic-pharmacodynamic modeling of the
      miotic effects of the opioids as a reliable and sensitive surrogate parameter of
      the central nervous opioid effects. Polymorphisms at an allelic frequency of > or
      =5% (n=310) were 118A>G in exon 1 (11.5%), the IVS2-31G>A (8.9%) and IVS2-691C>G
      (44.5%) SNPs in intron 2. The 118A>G SNP significantly increased the values of
      EC50 by a factor of more than 2 (non-mutated: EC50,morphine=30 nmol/l,
      EC50,M6G=750 nmol/l, 118G carriers: EC50,morphine=66 nmol/l, EC50,M6G=1650
      nmol/l), whereas the IVS2-691C>G SNP had no effect. Based on morphine and M6G,
      the present analysis encourages focusing on the 118A>G SNP when investigating the
      role of OPRM1 mutations for the activity of opioid analgesics. Other OPRM1
      mutations are probably less important either owing to low allelic frequency or
      due to poor indications for functional consequences. This applies to opioid
      potency in the context of opioid therapy but not to pain processing or substance
      addiction, in which opioid receptors are involved but other or additional OPRM1
      mutations may be important.

PMID- 16415920
TI  - Pharmacogenetics and pharmacogenomics: origin, status, and the hope for
      personalized medicine.
AB  - Pharmacogenetics arose with studies of single genes, which had major effects on
      the action of particular drugs. It turned into pharmacogenomics through
      realization that the controls of most drug responses are multifactorial. Then,
      variable gene expression posed new problems, for example what do drugs do to
      genes, or how useful is any genetic pretesting of a person? A common disease may
      be caused by different groups of genes in different people, who therefore require
      different drugs for treatment. Personalized medicine is currently represented by
      a physician's attention to a patients age, sex, or ethnic background, that is
      groups showing smaller genetic variation than is typical for general humanity.
      Occasionally, there is also the use of single-gene pretesting of a patient before
      drug administration. Over time, improvements in multigenic testing promise to
      increase the role of personalized medicine. However, the many pharmacogenomic
      complexities, and particularly time-dependent changes of gene expression, will
      never allow personalized medicine to become an error-free entity.

PMID- 16415921
TI  - A marker for Stevens-Johnson syndrome ...: ethnicity matters.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but
      severe cutaneous adverse drug reactions, which can be caused by a certain number
      of specific drugs among which is carbamazepine, an antiepileptic agent. A very
      strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been
      described in the Han Chinese population. Here in, we report preliminary results
      from a European study (RegiSCAR) of 12 carbamazepine-induced SJS/TEN cases (nine
      French and three German). Among these only four had a HLA-B*1502 allele.
      Remarkably, these four patients had an Asian ancestry, whereas the others did not
      as far as we have ascertained. This shows that although the HLA region may
      contain important genes for SJS, the HLA-B*1502 allele is not a universal marker
      for this disease and that ethnicity matters.

PMID- 16415922
TI  - Use of genomic signatures in therapeutics development in oncology and other
      diseases.
AB  - Pharmacogenomics is the science of determining how the benefits and adverse
      effects of a drug vary among a target population of patients based on genomic
      features of the patient's germ line and diseased tissue. By identifying those
      patients who are most likely to respond while eliminating serious adverse
      effects, the therapeutic index of a drug can be substantially increased. This may
      facilitate demonstrating the effectiveness of the drug and may avoid subsequent
      problems due to serious adverse events. Our objective here is to provide clinical
      trial designs and analysis strategies for the utilization of genomic signatures
      as classifiers for patient stratification or patient selection in therapeutics
      development. We review methods for the development of genomic signature
      classifiers of treatment outcome in high-dimensional settings, where the number
      of variables available for prediction far exceeds the number of cases. The split
      sample and cross-validation methods for obtaining estimates of prediction
      accuracy in developmental studies are described. We present clinical trial
      designs for utilizing genomic signature classifiers in therapeutics development.
      The purpose of the classifier is to facilitate the identification of groups of
      patients with a high probability of benefiting from it and avoiding serious
      adverse events. We distinguish exploratory analysis during the development of the
      genomic classifier from prospective planning and rigorous testing of therapeutic
      hypotheses in studies that utilize the genomic classifier in therapeutics
      development. We discuss a variety of clinical trial designs including those
      utilizing specimen collection and assay prospectively for newly accrued patients
      and those involving a prospectively planned analysis of archived specimens from a
      previously conducted clinical trial. Our discussion of the development and use of
      classifiers of efficacy is mostly focused on applications in oncology using
      classifiers based on biomarkers measured in tumors. Some of the same
      considerations apply, however, to development of efficacy and safety classifiers
      in nononcologic diseases based on single-nucleotide germline polymorphisms.

PMID- 16415923
TI  - Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after
      spinal cord injury in rats.
AB  - STUDY DESIGN: An experimental animal model was used to assess spinal cord injury
      following lateral hemitransection at thoracic spinal cord level. OBJECTIVE: To
      determine whether extract of Ginkgo biloba (EGb) could have a neuroprotective
      effect in spinal cord injury (SCI) in rats. SETTING: Department of Biological
      Sciences and Biotechnology, Tsinghua University, China. METHODS: A total of 72
      adult rats were divided randomly into three groups: the EGb group, normal saline
      (NS) group, and sham operation group (sham group). After thoracic spinal cord
      hemitransection was performed at the level of the 9th thoracic vertebra (T9),
      rats in the EGb group were given 100 mg/kg EGb 761 daily, while rats in the NS
      group received NS. The rats in the sham group only underwent laminectomy without
      spinal cord hemitransection. At various time points after surgery, thoracic
      spinal cords were sampled and sliced for histochemistry, immunohistochemistry of
      inducible nitric oxide synthase (iNOS), and terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL) of apoptotic cells. RESULTS: Myelin
      staining showed that the area of cavities was small and the demyelinated zones
      were limited at and around the injury site of the spinal cord in the EGb group,
      while the area of cavities was large and the demyelinated zones were serious in
      the NS group. Nissl staining showed that the ratio of bilateral ventral horn
      neurons (transection side/uninjured side) in the EGb group was higher than that
      in the NS group (P<0.05). The apoptotic index and the percentage of iNOS-positive
      cells were lower in the EGb group than in the NS group. Furthermore, the
      percentage of iNOS-positive cells positively correlated with the apoptotic index
      (r( 2)=0.729, P<0.01) after SCI. CONCLUSION: This study demonstrated that EGb 761
      could inhibit iNOS expression and have neuroprotective effect by preventing nerve
      cells from apoptosis after SCI in rats.

PMID- 16415924
TI  - Leisure satisfaction and psychiatric morbidity among informal carers of people
      with spinal cord injury.
AB  - STUDY DESIGN: Cross sectional survey. OBJECTIVE: To examine the nature and
      prevalence of common mental disorders among informal carers of people with Spinal
      Cord Injury (SCI) and the association with their leisure satisfaction. SETTING:
      Christian Medical College, Vellore, Tamilnadu, India. METHODS: A cross-sectional
      survey of informal carers of people SCI at the Department of Physical Medicine
      and Rehabilitation. Fifty-three informal carers of people with SCI were
      interviewed using the Revised Clinical Interview Schedule to assess psychiatric
      morbidity, and using the Leisure Satisfaction Scale to measure leisure and
      contentment. Data on carers with psychiatric morbidity were compared to those
      without common mental disorders using univariate and multivariate statistics.
      RESULTS: Study reported a high morbidity (53%), with most consistent diagnoses of
      depression and anxiety. Carers who were spouses, women, currently married and
      those with lower education had greater psychiatric morbidity and lesser leisure
      satisfaction, even after adjusting for age and education using logistic/linear
      regression. Age, occupation, residence, socioeconomic status, type and duration
      of SCI were not associated with either morbidity or leisure satisfaction.
      CONCLUSION: Many carers of people with SCI suffer from psychiatric morbidity and
      also have low scores on leisure satisfaction.

PMID- 16415925
TI  - Actin-dependent movement of bacterial pathogens.
AB  - Listeria, Rickettsia, Burkholderia, Shigella and Mycobacterium species subvert
      cellular actin dynamics to facilitate their movement within the host cytosol and
      to infect neighbouring cells while evading host immune surveillance and promoting
      their intracellular survival. 'Attaching and effacing' Escherichia coli do not
      enter host cells but attach intimately to the cell surface, inducing motile actin
      rich pedestals, the function of which is currently unclear. The molecular basis
      of actin-based motility of these bacterial pathogens reveals novel insights about
      bacterial pathogenesis and fundamental host-cell pathways.

PMID- 16415926
TI  - Microbial biogeography: putting microorganisms on the map.
AB  - We review the biogeography of microorganisms in light of the biogeography of
      macroorganisms. A large body of research supports the idea that free-living
      microbial taxa exhibit biogeographic patterns. Current evidence confirms that, as
      proposed by the Baas-Becking hypothesis, 'the environment selects' and is, in
      part, responsible for spatial variation in microbial diversity. However, recent
      studies also dispute the idea that 'everything is everywhere'. We also consider
      how the processes that generate and maintain biogeographic patterns in
      macroorganisms could operate in the microbial world.

PMID- 16415927
TI  - Long-term survival during stationary phase: evolution and the GASP phenotype.
AB  - The traditional view of the stationary phase of the bacterial life cycle,
      obtained using standard laboratory culture practices, although useful, might not
      always provide us with the complete picture. Here, the traditional three phases
      of the bacterial life cycle are expanded to include two additional phases: death
      phase and long-term stationary phase. In many natural environments, bacteria
      probably exist in conditions more akin to those of long-term stationary-phase
      cultures, in which the expression of a wide variety of stress-response genes and
      alternative metabolic pathways is essential for survival. Furthermore, stressful
      environments can result in selection for mutants that express the growth
      advantage in stationary phase (GASP) phenotype.

PMID- 16415928
TI  - Coronavirus infection of the central nervous system: host-virus stand-off.
AB  - Several viruses infect the mammalian central nervous system (CNS), some with
      devastating consequences, others resulting in chronic or persistent infections
      associated with little or no overt pathology. Coronavirus infection of the murine
      CNS illustrates the contributions of both the innate immune response and specific
      host effector mechanisms that control virus replication in distinct CNS cell
      types. Despite T-cell-mediated control of acute virus infection, host regulatory
      mechanisms, probably designed to protect CNS integrity, contribute to the failure
      to eliminate virus. Distinct from cytolytic effector mechanisms expressed during
      acute infection, non-lytic humoral immunity prevails in suppressing infectious
      virus during persistence.

PMID- 16415929
TI  - The bacterial segrosome: a dynamic nucleoprotein machine for DNA trafficking and
      segregation.
AB  - The genomes of unicellular and multicellular organisms must be partitioned
      equitably in coordination with cytokinesis to ensure faithful transmission of
      duplicated genetic material to daughter cells. Bacteria use sophisticated
      molecular mechanisms to guarantee accurate segregation of both plasmids and
      chromosomes at cell division. Plasmid segregation is most commonly mediated by a
      Walker-type ATPase and one of many DNA-binding proteins that assemble on a cis
      acting centromere to form a nucleoprotein complex (the segrosome) that mediates
      intracellular plasmid transport. Bacterial chromosome segregation involves a
      multipartite strategy in which several discrete protein complexes potentially
      participate. Shedding light on the basis of genome segregation in bacteria could
      indicate new strategies aimed at combating pathogenic and antibiotic-resistant
      bacteria.

PMID- 16415930
TI  - Helicobacter pylori phase variation, immune modulation and gastric autoimmunity.
AB  - Helicobacter pylori can be regarded as a model pathogen for studying persistent
      colonization of humans. Phase-variable expression of Lewis blood-group antigens
      by H. pylori allows this microorganism to modulate the host T-helper-1-cell
      versus T-helper-2-cell response. We describe a model in which interactions
      between host lectins and pathogen carbohydrates facilitate asymptomatic
      persistence of H. pylori. This delicate balance, favourable for both the pathogen
      and the host, could lead to gastric autoimmunity in genetically susceptible
      individuals.

PMID- 16415931
TI  - [Medicine and science in perspective].

PMID- 16415932
TI  - [It was not possible to save the life--or?].

PMID- 16415933
TI  - [Organisation of trauma services--major improvements over four years].
AB  - BACKGROUND: Despite recent developments in trauma care, it is estimated that 10
      to 15% of deaths after injury are avoidable and caused by errors in the initial
      hospital phase of treatment. In 2000 it was found that a number of Norwegian
      hospitals lacked procedures and protocols. The situation in all hospitals
      delivering trauma care in Norway was reassessed. MATERIAL AND METHODS: In autumn
      of 2004, all 50 Norwegian trauma care hospitals were surveyed. Response was
      obtained from all. RESULTS: Trauma teams were found in 88% of all hospitals,
      compared to 52% in 2000. A parallel improvement was found in the use of paging
      criteria for trauma teams, use of trauma manuals and protocols, and designated
      patient charts. Targeted training of teams was done in 88% of the hospitals and
      54 % had arranged practical drills of trauma teams in the six months prior to the
      survey. Only minor differences were found between hospitals at different levels.
      Systematic audits were performed in only 27% of hospitals. INTERPRETATION: A
      major improvement has taken place during four years, and it is now possible to
      implement national trauma care guidelines. There is still a need for improved use
      of audits and team training.

PMID- 16415934
TI  - [Quality assessment of urine dip-slides in primary care].
AB  - BACKGROUND: In Norway, approximately 35% of surgery laboratories use dip-slides
      to assess bacteriuria. From 2000 to 2004 the Norwegian centre for quality
      assurance in primary health care (NOKLUS) has evaluated how office laboratories
      assess urine dip-slides. MATERIAL AND METHODS: Once a year participants receive
      inoculated and incubated dip-slides to read and report to NOKLUS. Target values
      are determined from assessments in four large microbiological laboratories.
      RESULTS: Knowledge of reading dip-slides is insufficient. Only 40% of the
      participants in the quality assessment program evaluate whether growth is gram
      negative or gram-positive, or take into account whether the growth is mono
      bacterial or mixed. Many participants send the dip-slide to microbiological
      laboratories for evaluation whenever growth is significant, also when the growth
      is mixed. INTERPRETATION: The programme shows that Norwegian office laboratories
      do not use all the information they can get from the dip-slide. There is a need
      for guidelines on this topic in general practice.

PMID- 16415935
TI  - [Patient satisfaction with two different types of bladder catheters].
AB  - BACKGROUND: The insertion of a urinary catheter may cause some discomfort or
      pain. This study was done in order to compare patient-perceived discomfort with
      two commonly used coated urinary catheters for in-out catheterisation. MATERIAL
      AND METHODS: A total of 196 women were randomised to be catheterised with one of
      two coated, hydrophilic catheters, either a Lofric or a SpeediCath catheter.
      Degree of discomfort was recorded on a 10 cm visual analogue scale. RESULTS AND
      INTERPRETATION: There was no difference in patient-perceived discomfort between
      the two catheters. The degree of discomfort was small with both catheters, with a
      median score of only 0.75 cm on the scale.

PMID- 16415936
TI  - [Advanced glycation end products and hyperglycaemia].
AB  - Hyperglycaemia leads to increased formation and accumulation of advanced
      glycation end products, and these molecules play an important role in the
      development of micro- and macrovascular complications in diabetes. The formation
      of advanced glycation end products are complex reactions that take place both
      intra- and extracellularly. Advanced glycation end products affect gene
      regulation by binding to receptors, but can also modify proteins, DNA and lipids
      directly. The amount in serum and tissues depends upon several factors. The
      extent of hyperglycaemia is the main determining factor for levels of glycation
      products in the body, but the ability to break down and excrete these products in
      the urine is also important. The most effective way of preventing late
      complications in diabetes caused by glycation products is strict regulation of
      blood sugar levels. Drugs that inhibit advanced glycation end products could
      potentially be important in the prevention of late complications in diabetes, but
      this needs further investigation.

PMID- 16415937
TI  - [Could intake of vitamins C and E inhibit development of Alzheimer dementia?].
AB  - BACKGROUND: Alzheimer dementia is a neurodegenerative disease characterised by
      loss of memory and other cognitive functions. Oxidative stress is a possible
      pathogenetic factor and the anti-oxidating vitamins C and E could therefore have
      a beneficial effect and reduce the damage caused by beta-amyloid. MATERIALS AND
      METHODS: The relevant literature (several observational studies and two clinical
      controlled trials) describing effects of vitamin C and E in Alzheimer dementia
      have been evaluated. RESULTS: Several observational studies in mostly healthy,
      elderly individuals have indicated that vitamin C and E, mainly from food as well
      as the combination of high doses of the same vitamins, may have beneficial effect
      on the development of Alzheimer dementia. One clinical controlled trial in
      patients with manifest Alzheimer dementia, in which vitamin E 2000 mg/day was
      given as the only vitamin, has to a certain extent confirmed these results.
      INTERPRETATION: A causal relationship between intake of the vitamins and
      Alzheimer dementia has not been clarified. The correct dosages are not known, but
      a diet rich in these vitamin could probably reduce the risk of dementia. With a
      high intake of vitamin E, the addition of vitamin C is necessary.

PMID- 16415938
TI  - [Warfarin treatment in a general practice].
AB  - BACKGROUND: Warfarin treatment gives a well-documented reduction of the risk of
      thrombosis, but makes the patients more liable to bleedings. In Norway most
      patients are treated in general practice. MATERIAL AND METHODS: This study
      describes a 16-year-material (1988-2003) of 427 patients on warfarin in a
      practice with five general practitioners, based on retrospective analysis of
      patient files. A more detailed survey was done for the last four years (260
      patients). RESULTS: The prevalence of warfarin treatment in the practice
      increased from 0.9% to 2.7%, mostly because of increased treatment of atrial
      fibrillation. The average age of patients increased from 64 years to 72 years.
      57% of the INR measurements were within therapeutic range. There were 16
      haemorrhages pr 100 patient years with the majority occurring on therapeutic INR
      values. 14 serious haemorrhages were registered (2.4 pr 100 patient years),
      including seven cerebral haemorrhages resulting in three permanent cases of
      paralysis and one death. 14 patients had new disease diagnosed due to the
      bleeding. Only 1 patient experienced a venous thrombosis during 572 patient years
      of treatment. However, on 3 occasions thrombosis occurred shortly after
      termination of warfarin treatment. INTERPRETATION: Prevalence of warfarin
      treatment was higher than usual. The numbers of INR values within therapeutic
      range and numbers of serious bleedings were comparable to other studies. In spite
      of risk of haemorrhage, warfarin is a worthwhile treatment and can be carried out
      in general practice.

PMID- 16415939
TI  - [Medico-legal assessments of complaints against general practitioners].
AB  - BACKGROUND: The aim of this study was to assess the predictability in the
      processing of complaints from patients against general practitioners. We also
      wanted to identify medical issues and situations prone to elicit complaints and
      possible reactions. MATERIAL AND METHODS: This study includes cases received by
      the Norwegian Board of Health from county governors during two years (n = 107).
      One half of the cases consists of complaints that were remitted due to the
      complainants' objection to county governors' rejections. The other half is cases
      remitted when county governors assumed that the GP should be given a reaction. In
      the medico-legal assessment of the cases it was checked whether the guidelines
      for such cases had been observed. RESULTS: The guidelines had been observed in
      all but two cases. The relation between indefensible action and insufficient
      clinical judgment is highly significant (p < 0.001). This also holds for the
      relation between reactions following an on call-situation and the general
      practitioner not having Norwegian as his or hers first language. The handling of
      female patients leads to significantly less reactions than those of male
      patients. The county governors' assessments coincided to a limited degree with
      the assessments made by the Norwegian Board of Health. INTERPRETATIONS: The
      assessments of complaints made against GPs are coherent and predictable and may
      be a source of learning from mistakes. The relation between reaction following an
      on call-situation and the GP not having Norwegian as his/hers first language
      should elicit actions on several levels. The lack of conformity between the
      county governors and the Norwegian Board of Health in assessing these cases
      indicates that a two-step processing is not appropriate.

PMID- 16415940
TI  - [A midwife-led birthing unit].
AB  - BACKGROUND: The Alternative Birth Centre (ABC) is a midwife-led unit which offers
      low-risk women integrated, individualised antenatal, intrapartum and postpartum
      care. MATERIAL AND METHODS: The study included 432 women who received their care
      at the ABC from November 1997 until July 2000. Demographic information and
      details about antenatal care were recorded for all women. Information about
      labour, delivery and the postnatal period were recorded for the 341 women who
      started their labour at the ABC. RESULTS: Of the 432 women who started their care
      at the ABC, 265 (61.3 %) gave birth there, 100 (38 %) were primiparous while 165
      (62.3 %) were multiparous. 84 (19.4 %) women were not suitable for birth at the
      ABC for reasons such as preterm birth, postterm pregnancies, breech presentation
      and preeclampsia, and were referred back to their own hospital during pregnancy.
      Among the 341 women that started labour at the ABC, 76 (22 %) were transferred to
      the obstetrical department during labour. Three reasons accounted for 88 % off
      all transfers during labour: failure to progress (n = 34, 44.7 %), need for
      continuous fetal monitoring (n = 20, 26.3 %), and the need for pharmacological
      pain relief (n = 13, 17.1 %). Of the 76 women transferred in labour, 42 had a
      spontaneous vaginal birth while 36 (44.7 %) women had an operative delivery, 14
      caesarean section, 16 vacuum extraction and 1 of them forceps delivery. One baby
      born at the ABC had an Apgar score below 7 at 5 min. ABC is a safe alternative to
      standard care for low-risk women.

PMID- 16415941
TI  - [The breakthrough series on Cesarean section].
AB  - BACKGROUND: The "breakthrough series" on caesarean section was organised in
      Norway in 1998/99 in response to professional concerns about rising caesarean
      section rates and the public debate about the topic. The aim was to gain more
      information and to reduce the inter-hospital variation of caesarean section
      rates. MATERIAL AND METHODS: Detailed information about 3000 caesarean sections
      (70% of all caesarean sections in Norway during the study period of 7 months) was
      collected. Twenty-four departments participated and were involved in a quality
      improvement process. RESULTS: In 1998 the caesarean section rate among the
      participating departments was 13.5% (inter-hospital variation 8.6% to 20.4%). In
      2002 the rate was 15.7% (inter-hospital variation 11.0%-24.5%). The most frequent
      indications were fetal stress, prolonged labour, previous caesarean section,
      breech presentation and maternal request. Of the women with a previous caesarean
      section, 45.5% had a new caesarean section in their next pregnancy. Complications
      occurred in 21% of all procedures; risk factors were general anaesthesia, low
      gestational age, fetal macrosomia and degree of cervical dilation.
      INTERPRETATION: The project highlighted quality improvement work and
      interdisciplinary working processes and led to more knowledge about caesarean
      section. The inter-hospital variation was unchanged four years after the project.

PMID- 16415942
TI  - [Self-reported walking, balance testing and risk of fall among the elderly].
AB  - BACKGROUND: Falls represent an important health problem among the elderly.
      Balance testing as well as registration of self-reported balance problems may be
      appropriate in order to predict the risk of future falls. MATERIALS AND METHODS:
      Self-reported walking was assessed in 307 randomly selected women 75 years or
      older living at home. The women underwent testing of gait and balance and were
      followed up for one year with respect to falls and fall-related injuries.
      RESULTS: 155 of the women fell during the observation period; 308 falls were
      reported. 13% of the falls resulted in a fracture. Factor analysis identified
      five anamnestic questions measuring the same latent construct. The sum score of
      this self-reported walking index correlated highly with simple balance tests. A
      poor result on the walking index indicated a high risk of falling (odds ratio
      (OR) 1.83, 95% confidence interval 1.41-2.30) and of fall-related fractures (OR
      2.65, 95 % CI 1.27-5.05) the subsequent year. The areas under the ROC curves
      (receiver-operating characteristics) were, however, only .57 for falls and .61
      for fractures. INTERPRETATION: Simple questions give useful information on the
      risk of falls and fall-related fractures among elderly women.

PMID- 16415943
TI  - [Hyperprolactinemia induced by antipsychotic agents].

PMID- 16415944
TI  - [Intelligent design].

PMID- 16415945
TI  - [How to make warfarin treatment successful?].

PMID- 16415946
TI  - [Statistics and Tidsskriftet].

PMID- 16415948
TI  - [Sense and sensibility in delivery care].

PMID- 16415949
TI  - [Statistics in medical research].

PMID- 16415953
TI  - [Productivity and quality].

PMID- 16415954
TI  - [Treatment of patients with acute coronary syndrome in Norwegian hospitals].

PMID- 16415964
TI  - N-terminal segments are the functional domains of CLN3-encoded battenin for
      protein interactions.
AB  - OBJECTIVE: Batten disease (BD), the juvenile form of neuronal ceroid
      lipofuscinosis (NCLs), is pathological characterized by finding lysosomal storage
      of autofluorescent lipofuscins with unique ultrastructural profiles. The gene
      underlying BD is designated CLN3 and encodes a protein, Battenin, of unknown
      function that localizes in lysosomes and/or mitochondria. Previously, we
      hypothesized that Battenin associates with other membrane protein(s) to form a
      membrane complex. Dysfunction of this complex could result in the pathological
      changes of BD, and possibly in other NCLs. Two such membranous proteins, the slow
      and fast Battenin-interactive proteins (BIPs and BIPf) of unknown functions, have
      been identified. In this study, we have characterized the functional domains of
      Battenin that interact with both BIP proteins. METHODS: Protein-protein
      interactions with a yeast two-hybrid system were employed. A "deletion assay" was
      employed to localize the interactive segment(s). Different lengths of cDNA
      sequences lacking exon 1-5 were used to express CLN3-encoded proteins lacking N
      terminal segments in the yeast two-hybrid system. N-terminal exons of CLN3 were
      deleted with PCR-cloning strategies. RESULTS: We eliminated the possibility of
      interacting domains from the exon 7-encoded region because both Battenin and
      mBattenin interact with the BIP proteins. We have shown that peptide sequences
      encoded by exons 2 and 4 of CLN3 gene include the functional domains by which
      Battenin interacts with the BIP proteins. CONCLUSION: Our studies provide
      evidence that the N-terminus of Battenin is the functional domain for these
      protein interactions.

PMID- 16415965
TI  - Genotype-phenotype analyses of classic neuronal ceroid lipofuscinosis (NCLs):
      genetic predictions from clinical and pathological findings.
AB  - OBJECTIVE: Genotype-phenotype associations were studied in 517 subjects
      clinically affected by classical neuronal ceroid lipofuscinosis (NCL). METHODS:
      Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological
      symptoms, and electron microscope (EM) profiles. RESULTS: The most common initial
      symptom leading to a clinical evaluation was developmental delay (30%) in NCL1,
      seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent
      of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing
      EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing
      profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles.
      The mixed-type EM profile was found in approximately one-third of the NCL cases.
      DNA mutations within a specific CLN gene were further correlated with NCL
      phenotypes. Seizures were noticed to associate with common mutations 523G>A and
      636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in
      NCL1. Vision loss was the initial symptom in all types of mutations in NCL3.
      Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1
      (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of
      NCL3 (juvenile form) cases. CONCLUSION: Our data provide an overall picture
      regarding the clinical recognition of classical childhood NCLs. This may assist
      in the prediction and genetic identification of NCL1-3 via their characteristic
      clinical features.

PMID- 16415966
TI  - Chromosomal abnormalities and adverse pregnancy outcome with maternal serum
      second trimester triple screening test for fetal Down syndrome in 4,860 Chinese
      women.
AB  - OBJECTIVE: To investigate the efficiency of maternal serum triple screening for
      the genetic abnormality in second-trimester and the morbidity of adverse
      pregnancy outcome in false positive results of the test. METHODS: A total of
      4,680 pregnant women with singleton pregnancies assigned in Obs & Gyn Hospital,
      Fudan University, underwent triple screening test (alpha fetoprotein, AFP; human
      chorionic gonadotropin, HCG and unconjugated estriol, uE3) by fluorescence enzyme
      immunoassay between 2003 and 2005. The valid MoM (Multiples of Median) value of
      mid-trimester serum AFP, uE3, and hCG and risk assessments was provided by
      Beckman Coulter Co. when applied in the prenatal Down syndrome screening service.
      The study compares the incidence of chromosomal abnormalities with Down syndrome
      in screen positive women and compares to the MoM value established in the
      literature. The risks of having a fetus with congenital abnormalities or of
      developing obstetric complications in the screen positive women with their
      matched controls. RESULTS: The MoM values for the triple tests of our study are
      similar to established values of literature. Only 51.01% women with pregnancies
      agree to receive screening. Amniocentesis utilization rate was 55.12% in the
      screen-positive pregnancies. The false positive rate was 6.89% and the median of
      maternal age of the women was 28.13 (range 19 to 49) years old. Chromosomal
      abnormalities were identified in 21 pregnancies, including 9 cases of trisomy 21.
      The detection rate was 77.77%. Pregnancies with positive screening results had a
      significantly higher risk of adverse outcomes than those with negative results
      (P< 0.05). Whereas there was no difference in the incidences of fetal congenital
      appearance or skeleton abnormality. CONCLUSION: Adjusting MoM values of local
      unaffected populations is limited to increasing the detection rate. Because
      chromosomal defects have variable exhibitions, amniocentesis utilization is still
      a choice for screen-positive pregnancies. Screen-positive pregnancies had
      increased risk of chromosomal abnormalities.

PMID- 16415967
TI  - Prenatal molecular diagnosis of Duchenne and Becker muscular dystrophy.
AB  - OBJECTIVE: Duchenne and Becker muscular dystrophy (DMD/BMD) is an X-linked lethal
      recessive disease caused by mutations in the dystrophy gene. There is no
      efficient treatment for this serious and disabling disease. We established a
      combination method to detect carriers and perform prenatal diagnosis. METHODS: In
      our study, from 1994 to 2005, using a different combination of 5 methods,
      including SRY gene amplification, multiplex PCR, multiplex Fluorescence PCR
      capillary electrophoresis, multiplex ligation-dependent probe amplification
      (MLPA) and linkage analysis of short tandem repeats (STR), 36 prenatal diagnosis
      were performed for pregnancies at risk of having a DMD/BMD baby through
      amniocentesis. RESULTS: Fourteen out of 21 male fetuses were found to be affected
      and respective pregnancies were terminated. A combined diagnostic rate of 83% was
      achieved for 30 cases with deletions, duplications, and non-deletion mutations
      after tested by more than one method. CONCLUSION: Using a combined method, we can
      diagnoses patients and carriers in DMD families, and perform prenatal diagnosis
      for the risk fetus. MLPA provides a simple, rapid and accurate method for
      deletions and duplications of all the 79 DMD exons. MLPA method for DMD diagnosis
      is the first report in our country.

PMID- 16415968
TI  - The frequency of chromosome 7q interstitial deletions associated with B-cell
      lymphoproliferative disorders is substantially high among hematological
      malignancies.
AB  - OBJECTIVE: To study the frequency of interstitial 7q deletions in B-cell
      lymphoproliferative disorders (B-LPDs). METHODS: Cases were collected from the
      clinical laboratory diagnosis database at USLabs/LabCorp over the past two years
      (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were
      then reviewed. Interstitial deletions in the long arm of chromosome 7 were
      further investigated according to the indications for clinical laboratory studies
      and flow cytometry findings. The final clinical diagnosis for each case was
      obtained from the referring physician. RESULTS: A total of 19,483 cases were
      included in this series. Eighty-five cases were observed to have either terminal
      or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had
      interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs
      were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated
      with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic
      leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome
      7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32
      region. CONCLUSION: (1) The frequency of 7q interstitial deletions associated
      with B-LPDs is substantially high; (2) 7q interstitial deletions are not uncommon
      in B-CLL.

PMID- 16415969
TI  - Study of microsatellite instability in epithelial ovarian tumors.
AB  - OBJECTIVE: To evaluate the frequency of MSI in epithelial ovarian tumors and its
      relationship with clinicopathologic features. METHODS: Ninety fresh specimens of
      epithelial ovarian tumors, including 74 primary and 16 secondary tumors, were
      collected. Microsatellite analysis was carried out using 5 mono-and dinucleotide
      markers from the National Cancer Institute Consensus Panel by fluorescence
      labeled polymerase chain reaction. RESULTS: Of 90 epithelial ovarian tumors
      analyzed, 18 demonstrated a high level of microsatellite instability (MSI-H), 30
      demonstrated a low level of microsatellite instability (MSI-L), and the remaining
      42 exhibited microsatellite stability (MSS). Frequency of microsatellite
      instability (MSI) at loci BAT-25 was higher than that at any other loci. No
      correlation was found between MSI level and patient age, tumor type, tumor
      differentiation (P>0.05). But the microsatellite instability-high phenotype
      correlates with clinical stage. It tended to occur more frequently in early-stage
      tumors (P=0.03). CONCLUSION: The frequent MSI in epithelial ovarian tumors
      suggests that it is an early event to involve in the development of epithelial
      ovarian tumors.

PMID- 16415970
TI  - The genotype and phenotype studies of 40 Chinese patients with X-linked
      adrenoleukodystrophy (X-ALD).
AB  - OBJECTIVE: To elucidate the phenotype and the genotype-phenotype correlations in
      Chinese patients with X-linked adrenoleukodystrophy (X-ALD). METHODS: Clinical
      features of 40 Chinese patients with X-ALD were studied and mutation spectrums
      were investigated by polymerase chain reaction (PCR) and sequencing. RESULTS:
      Among these patients, four were siblings from two unrelated families, the others
      were unrelated. There were 31 cases with childhood cerebral (CCALD), 8 cases with
      adolescent cerebral (ACALD) and 1 case with adrenomyeloneuropathy (AMN). Visual
      impairment, which presented in 12 cases (30%), was the most common initial
      symptom. Nine (69%) of 13 cases who had hydrocortisone and ACTH measured showed
      adrenal insufficiency. By follow-up date, 19 cases (47.5%) were dead. The
      interval from onset to death varied from 1 to 6 years and the average were 3.3
      years. The mean age at death was 10.5 years. Eleven cases (27.5%) were in
      vegetable state. The mean interval from onset to apparently vegetable state was
      2.8 years (range from 1 to 6 years). Four cases had progressive neurological
      disability. Four cases were lost follow-up. One case with CCALD and one case with
      ACALD progressed slowly. The courses of the disease of these two patients were 5
      years and 15 years respectively. Thirty five mutations were identified in 40
      cases. Most were located within exon 1-3 (40%, 16/40) and exon 6-8 (42%, 17/40).
      There is a distinct clustering of missense mutations in exon 6 (17%, 7/40). Five
      types of mutations were associated with CCALD, three with ACALD and a missense
      mutation was identified in the patients with AMN. The two patients with long
      disease courses had a missense mutation c.1559 T>A and a nonsense mutation c.1785
      G>A respectively. The siblings with similar manifestations and onset age were
      observed in two families, whose mutations were c.887 A>G and c.1028 G>T.
      CONCLUSION: The phenotypes, disease severity and rate of neurodegeneration could
      not be predicted by the nature of mutations.

PMID- 16415971
TI  - Decision forest analysis of large-scale sib-pair identical-by-decent profiles for
      locating the underlying disease genes for alcoholism in human.
AB  - OBJECTIVE: To extract the relevant SNPs for alcoholism using sib-pair IBD
      profiles of pedigrees. METHODS: We used the ensemble decision approach, a
      supervised learning approach based on decision forests, to locate alcoholism
      relevant SNPs using genome-wide SNP data. RESULTS: Application to a publicly
      available large dataset of 100 simulated replicates for three American
      populations (http://www.gaworkshop.org/) demonstrates that the proposed approach
      has successfully located all of the simulated true loci. CONCLUSION: The
      numerical results establish the proposed decision forest analysis to be a
      powerful and practical alternative for large-scale family-based association
      study.

PMID- 16415973
TI  - No mutation was detected in the LMNA gene among sporadic Charcot-Marie-Tooth
      patients.
AB  - OBJECTIVE: To intensively investigate sporadic CMT patients, we have analyzed the
      LMNA gene in this study in a series of 32 unrelated CMT patients. METHODS: Twelve
      exons of the LMNA gene were amplified from genetic DNA. PCR products of each exon
      were analyzed by single strand conformational polymorphism (SSCP). RESULTS: No
      abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected.
      CONCLUSION: The CMT diseases resulted from the mutations of LMNA gene were rare.

PMID- 16415972
TI  - Novel strategies to identify relevant molecular signatures for complex human
      diseases based on data of identical-by-decent profiles and genomic context.
AB  - OBJECTIVE: To develop novel strategies to identify relevant molecular signatures
      for complex human diseases based on data of identical-by-decent profiles and
      genomic context. METHODS: In the proposed strategies, we define four relevancy
      criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference,
      averaged IBD difference for window, Z curve and averaged slope for window.
      RESULTS: Application of these criteria and permutation test to 100 simulated
      replicates for two hypothetical American populations to extract the relevant SNPs
      for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the
      proposed strategies have successfully identified most of the simulated true loci.
      CONCLUSION: The data mining practice implies that IBD statistic and genomic
      context could be used as the informatics for locating the underlying genes for
      complex human diseases. Compared with the classical Haseman-Elston sib-pair
      regression method, the proposed strategies are more efficient for large-scale
      genomic mining.

PMID- 16415974
TI  - Prognostic factors and survival of stage IB-IIA cervical cancer.
AB  - OBJECTIVE: This study investigated the prognostic significance of age at
      diagnosis, stage, tumor subtype, pelvic lymph node metastasis (PLNM), lymph
      vascular space involvement (LVSI), presence or absence of deep cervical stromal
      invasion (DCSI) in stage IB-IIA cervical cancer patients. It also investigated
      the inter-relationship among these factors. METHODS: 152 patients treated with
      radical hysterectomy plus pelvic lymphadenectomy were followed up for a median of
      49 months and were evaluated retrospectively. RESULTS: The 5-year overall
      survival rate was 84.8%. The distribution of age at diagnosis is of bimodal
      shape, peaking at 42 and 68 years, respectively. Tumor subtype, PLNM, DCSI, and
      LVSI were found to be significant prognostic factors individually. After
      multivariate analysis, only tumor subtype and PLNM were found to be independent,
      significant prognostic factors for survival. The prognostic importance of LVSI
      appeared to be eclipsed by the presence of PLNM. DCSI was statistically related
      with FIGO stage, LVSI and PLNM. CONCLUSION: Tumor subtype and PLNM are the two
      most important independent prognostic factors for stages IB-IIA cervical cancer.
      Some prognostic factors are inter-related and may reflect different facets of
      tumor progression.

PMID- 16415976
TI  - 9p subtelomere deletion: pathogenic mutation or normal variant?
AB  - We report an apparently benign familial 9p subtelomere deletion identified using
      chromosome-arm-specific subtelomere probes in a patient with multiple congenital
      anomalies. Our experience demonstrated that the discovery of a subtelomeric
      deletion and/or duplication does not always guarantee the identification of the
      etiology for the patients phenotype and a positive finding with subtelomere
      probes should always be followed by parental study with the same probe in order
      to distinguish a disease causing alteration from a benign familial polymorphism.

PMID- 16415975
TI  - Comparison of efficacy and toxicity profile between intraperitoneal and
      intravenous topotecan in human ovarian cancer xenografts.
AB  - OBJECTIVE: To compare the therapeutic and toxic profile of topotecan given
      intraperitoneally with intravenously in human ovarian cancer xenografted into
      athymic nude mice. METHOD: Eighty female Balb-c/nu-nu mice were randomized
      assigned into eight groups (n=10). Xenografts resulted from intramesentery
      injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of
      intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on
      day 7. Animals scheduled for topotecan i.p. received intraperitoneal application
      of topotecan (1.5 mg/kg x 2, 3.0 mg/kg x 2, 6.0 mg/kg x 2 or 10.0 mg/kg x 1).
      Animals scheduled for topotecan i.v. received intravenous administration of
      topotecan (6.0 mg/kg x 2 or 10.0 mg/kg x 1). Two weeks after drug application
      animals were killed. Tumor growth inhibition were assessed and compared with
      untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity
      was determined by loss of body weight. Cell cycle division and apoptosis after
      drug administration was determined by flow cytometric analysis. RESULTS: In a
      panel of ten tumour xenografts, intraperitoneal topotecan was significantly more
      effective than intravenous administration. The toxicity profile suggested a
      better tolerability in terms of weight loss after intraperitoneal administration
      than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an
      optimal treatment for ovarian cancer and well tolerated by mice with no signs of
      acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent
      apoptosis. No significant difference among mice treated with topotecan
      intraperitoneally or intravenously or cisplatin was observed in term of apoptosis
      and cell cycle perturbation. CONCLUSION: The results may have implications for
      the future design of clinical studies on intraperitoneal application of
      topotecan. It suggests that apoptosis and cell cycle perturbation play an limited
      role in the mechanism of topotecan administration.

PMID- 16415977
TI  - Medical genetic issues in clinical of pediatric neurology practice:a history of
      pediatrics in Peking University First Hospital.
AB  - The Department of Pediatrics of Peking University First Hospital has a long term
      of outstanding history. It was established about 60 years ago. After the division
      of pediatric neurology (DPN) had been established in 1960s, it had been assigned
      to cover genetic disorders. During the recent 20 years, efforts have been put on
      three aspects: (1) Pediatric neurology clinical service and education; (2)
      research studies of childhood epilepsies and pediatric neurogenetic disorders;
      and (3) development of a strong DPN team to establish a comprehensive pediatric
      neurological program. In this paper, we reviewed the history of the pediatric
      neurology division in our department, our clinical and research work and
      achievements for neurogenetic diseases.

PMID- 16415978
TI  - Lysosomal storage disorders.
AB  - Lysosomal storage disorders (LSDs) are genetic defects caused by lysosomal
      hydrolase deficiencies. These deficiencies lead to substrate accumulation
      affecting cells, tissues and organs. Detecting abnormal compound excretion and
      deficient enzymes assist diagnosis of these disorders for treatment and
      prevention. This mini review summarizes clinical presentations and diagnostic
      workup of LSDs and updates the new development in the area.

PMID- 16415979
TI  - Newborn screening of inherited metabolic diseases by tandem mass spectrometry.
AB  - Application of TMS technology in newborn screening has resulted in major
      expansion of disorder panel for metabolic diseases in recent years. This
      automated, multiplex testing methodology detects multiple analytes from single
      analysis of one blood spot, which leads to detection of 30-35 disorders of amino
      acids, organic acids, and fatty acids metabolism. The early identification of
      persons affected with inborn errors of metabolism has led to unexpected
      discoveries related to the natural history of the disorder or options for
      therapy. This article summarized (1) the basic principles of this technology and
      methodology. (2) Current status of application of this methodology in the United
      States, European countries and in China. (3) The positive impacts on the public
      health and advances in medical genetics. Finally (4) Challenges, issues and
      possible solutions. The purpose of this article aimed at introducing new
      technology and exploring the possibilities of implementing into developing
      countries where medical genetics is not developed and foreseeing the possible
      problems and obstacles.

PMID- 16415980
TI  - Clinical and genetic features of DYT1 and DYT5.
AB  - Dystonia is a syndrome which is characterized by sustained muscle contractions,
      producing twisting, repetitive, and patterned movements, or abnormal postures.
      According to genetic basis, dystonia is classified into 13 subtypes. We mainly
      discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary
      dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal.
      GTP cyclohydrolase 1 (GTPCH1)-deficient DRD (DYT5) is caused by the mutations of
      GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype
      and develop prenatal diagnosis for it.

PMID- 16415981
TI  - Principal genetic syndromes and autism: from phenotypes, proteins to genes.
AB  - Autism is a neurodevelopmental disorder characterized by impairments in social
      skills, language, and behavior. It is now clear that autism is not a disease, but
      a syndrome characterized by phenotypic and genetic complexity. The etiology of
      autism is still poorly understood. Available evidence from a variety of sources
      strongly suggests that many genetic disorders are frequently associated with
      autism for their similar phenotypes. Based on this fact, this review begins by
      highlighting several principal genetic syndromes consistently associated with
      autism (fragile X, tuberous sclerosis, Angelman syndrome, Pader-Willi syndrome,
      Rett syndrome, Down syndrome and Turner syndrome). These genetic disorders
      include both chromosome disorders and single gene disorders. By comparing the
      similar phenotype, protein marker and candidate genes, we might make some
      breakthrough in the mechanism of autism and other genetic disorders.

PMID- 16415982
TI  - Gene-specific countermeasures against Ebola virus based on antisense
      phosphorodiamidate morpholino oligomers.
AB  - The filoviruses Marburg virus and Ebola virus (EBOV) quickly outpace host immune
      responses and cause hemorrhagic fever, resulting in case fatality rates as high
      as 90% in humans and nearly 100% in nonhuman primates. The development of an
      effective therapeutic for EBOV is a daunting public health challenge and is
      hampered by a paucity of knowledge regarding filovirus pathogenesis. This report
      describes a successful strategy for interfering with EBOV infection using
      antisense phosphorodiamidate morpholino oligomers (PMOs). A combination of EBOV
      specific PMOs targeting sequences of viral mRNAs for the viral proteins (VPs)
      VP24, VP35, and RNA polymerase L protected rodents in both pre- and post-exposure
      therapeutic regimens. In a prophylactic proof-of-principal trial, the PMOs also
      protected 75% of rhesus macaques from lethal EBOV infection. The work described
      here may contribute to development of designer, "druggable" countermeasures for
      filoviruses and other microbial pathogens.

PMID- 16415983
TI  - Genome-scale identification of membrane-associated human mRNAs.
AB  - The subcellular localization of proteins is critical to their biological roles.
      Moreover, whether a protein is membrane-bound, secreted, or intracellular affects
      the usefulness of, and the strategies for, using a protein as a diagnostic marker
      or a target for therapy. We employed a rapid and efficient experimental approach
      to classify thousands of human gene products as either "membrane
      associated/secreted" (MS) or "cytosolic/nuclear" (CN). Using subcellular
      fractionation methods, we separated mRNAs associated with membranes from those
      associated with the soluble cytosolic fraction and analyzed these two pools by
      comparative hybridization to DNA microarrays. Analysis of 11 different human cell
      lines, representing lymphoid, myeloid, breast, ovarian, hepatic, colon, and
      prostate tissues, identified more than 5,000 previously uncharacterized MS and
      more than 6,400 putative CN genes at high confidence levels. The experimentally
      determined localizations correlated well with in silico predictions of signal
      peptides and transmembrane domains, but also significantly increased the number
      of human genes that could be cataloged as encoding either MS or CN proteins.
      Using gene expression data from a variety of primary human malignancies and
      normal tissues, we rationally identified hundreds of MS gene products that are
      significantly overexpressed in tumors compared to normal tissues and thus
      represent candidates for serum diagnostic tests or monoclonal antibody-based
      therapies. Finally, we used the catalog of CN gene products to generate sets of
      candidate markers of organ-specific tissue injury. The large-scale annotation of
      subcellular localization reported here will serve as a reference database and
      will aid in the rational design of diagnostic tests and molecular therapies for
      diverse diseases.

PMID- 16415985
TI  - [Arbovirus survey in some regions in Heilongjiang province].
AB  - BACKGROUND: Mosquitoes were collected in Heilongjiang province in 2002, four
      virus strains were isolated by inoculation of homogenates onto BHK cell lines.
      The viruses were identified. Multiple alignment and phylogenetic analysis were
      carried out by Clustal X (1.8) program.Amino acid (AA) analysis was carried out
      by GENEDOS (3.2). RESULTS: Biological characters of four newly isolated strains
      were examined and it was found that all of them could produce cytopathogenic
      effect (CPE) in BHK cells, killing sucking mice. Serological tests showed that
      all of these stains reacted positively to JEV antibodies. PrM and E gene regions
      were amplified and sequenced. Phylogenic analysis showed that all the newly
      isolated JEV strains belong to genotype III. Using the vaccine strains (SA14-14
      2) as control, analysis of the E gene of the new strains and two JEV strains (47,
      Ha-3) isolated previously from Heilongjiang province showed that these new
      strains' nucleotide sequence had a homology of up to 99.9% and the amino acid
      sequence homology up to 99.8%, respectively. Compared with the standard JE
      vaccine strain SA-14-14-2 and the four new strains, the nucleotide sequence
      homology was 97.3% and amino acid sequence homology was between 96.8% and 97.0%,
      respectively. Compared with vaccine strain, there were seven common variations in
      all the four newly isolated strains. CONCLUSION: Four JE virus strains were
      isolated in Heilongjiang province. As compared to the vaccine strain, six
      variations were found in the newly isolated strains at the eight sites relevant
      to the virulence of the virus.

PMID- 16415984
TI  - Comparative genomics of multidrug resistance in Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria
      commonly found in water and soil. This organism was susceptible to most
      antibiotics in the 1970s. It has now become a major cause of hospital-acquired
      infections worldwide due to its remarkable propensity to rapidly acquire
      resistance determinants to a wide range of antibacterial agents. Here we use a
      comparative genomic approach to identify the complete repertoire of resistance
      genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is
      epidemic in France, as well as to investigate the mechanisms of their acquisition
      by comparison with the fully susceptible A. baumannii strain SDF, which is
      associated with human body lice. The assembly of the whole shotgun genome
      sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb,
      respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a
      resistance island--the largest identified to date--in which 45 resistance genes
      are clustered. At the homologous location, the SDF strain exhibits a 20 kb
      genomic island flanked by transposases but devoid of resistance markers. Such a
      switching genomic structure might be a hotspot that could explain the rapid
      acquisition of resistance markers under antimicrobial pressure. Sequence
      similarity and phylogenetic analyses confirm that most of the resistance genes
      found in the A. baumannii strain AYE have been recently acquired from bacteria of
      the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in
      the discovery of 19 new putative resistance genes. Whole-genome sequencing
      appears to be a fast and efficient approach to the exhaustive identification of
      resistance genes in epidemic infectious agents of clinical significance.

PMID- 16415986
TI  - [Molecular epidemiology of Xinjiang hemorrhagic fever viruses].
AB  - BACKGROUND: To study the molecular biology of Xinjiang hemorrhagic fever (XHF)
      viruses, to explore its relationship with other Crimean-Congo hemorrhagic fever
      viruses, analyzing the epidemic origin and the tendency of geographic
      distribution of XHF. METHODS: The S partial segment from the patient and tick
      samples collected in 2001 and 2002 was tested by RT-PCR, the positive samples
      were sequenced directly. The nucleotide homology of S partial segment as well as
      the whole segments were analyzed and the phylogenetic tree of S and M gene
      segments was drawn by computer. RESULTS: All compared sequences of S partial
      segments from the patient and tick samples showed a high homology of nucleotide
      sequences. Phylogenetic tree divided all the analyzed viruses into three groups;
      Europe, African and Asian group. The Asian group can be divided further into
      another two branches: the middle Asian branch and the Chinese branch. All the
      Chinese isolates were clustered into one single group and was easy to be
      discriminated from the other isolates. The dividing of M segments seemed not
      completely related to the geographic origin of the viruses. CONCLUSION: M segment
      classification was not consistent to the geographic distribution of the viruses.
      S segments analysis showed the close relationship of genetic background between
      the patient isolates and the tick isolates. Besides, all the Chinese isolates
      have the common evolution route and the gene structure characteristics displayed
      the regional distribution pattern.

PMID- 16415987
TI  - [Isolation and identification of arboviruses from mosquito pools in Yunnan
      Province].
AB  - BACKGROUND: To survey arboviruses in Yunnan province. METHODS: Mosquitoes were
      collected from Yunnan Province in 2002 and 2004. Virus strains were isolated by
      the inoculation of homogenates of the mosquitoes onto BHK cell line. The isolated
      strains and their molecular biological characteristics were identified by real
      time PCR, reverse transcription-polymerase chain reaction (RT-PCR) and
      immunofluorescent antibody technique. RESULTS: Twelve strains of viruses
      producing CPE in BHK cells were isolated from 4810 mosquitoes. All the 12
      isolates were identified to be Japanese encephalitis viruses. Genotype analysis
      showed the new virus (DL-0437 strain) belonged to genotype III. CONCLUSION:
      Twelve strains of Japanese encephalitis viruses were isolated from mosquito pools
      collected in Yunnan. It was the first isolation of genotype III Japanese
      encephalitis viruses in Yunnan Province in recent years.

PMID- 16415988
TI  - [Molecular biological survey of tick-born arboviruses in southern part of
      Xinjiang].
AB  - BACKGROUND: To disclose the species and distribution of tick-borne arboviruses in
      the southern part of Xinjiang. METHOD: Totally 5045 ticks were collected from 36
      collecting sites of 23 places in the southern Xinjiang, which were made into cDNA
      pools with pd(N)6 primer through RT-PCR method. Then PCR was used to detect viral
      nucleotide sequence from cDNA. RESULTS: All 34 cDNAs showed negative to
      flavivirus and California serogroup virus primers; but nairovirus and primers
      derived from Xinjiang hemorrhagic fever virus had amplified and yielded some
      obvious bands corresponding to the nucleotide sequences of Xinjiang hemorrhagic
      fever virus. A phylogenetic analysis was done to the obtained partial sequences
      of L and S segments. CONCLUSION: Nucleotide sequences of Neither flaviviruses nor
      California serogroup viruses were detected from the samples. However partial L
      segment sequence was first reported in China. Phylogenetic analysis of partial L
      and S segments disclosed the molecular characteristic of Xinjiang hemorrhagic
      fever virus.

PMID- 16415989
TI  - [Molecular biological identification of Batai virus isolated in China].
AB  - BACKGROUND: To study the molecular characteristics of YN92-4 strain isolated from
      mosquitoes in Yunnan Province and define its classification. METHODS: The S
      segment of YN92-4 strain was amplified and sequenced by 2 different sets of
      primers. The phylogenic tree of S fragment was constructed by Phylip bio
      software. The amino acid sequences of N and NSs proteins were also studied.
      RESULTS: YN92-4 strain could be amplified by 2 sets of primers respectively, S
      segment showed a highest homology with Batai virus (X73464), reached 96.4%, the
      homology of protein N and NSs amio-acid sequence with Batai virus was 99.1% and
      98% respectively. CONCLUSION: The YN92-4 strain belongs to Batai virus, this is
      the first report of molecular biological identification of Batai virus in China.

PMID- 16415991
TI  - [Comparison and discrimination of the biological characteristics between West
      Nile virus and Japanese encephalitis virus].
AB  - BACKGROUND: To compare the biological characteristics of West Nile virus (WNV)
      and Japanese encephalitis virus (JEV), including cells sensitivity,
      pathogenicity, viral morphology, as well as the results of immunological and
      molecular biological detection. METHODS: Cytopathic effect (CPE) and
      pathogenicity were observed in C6/36 cells and in suckling mice inoculated
      intracerebrally with the WNV or JEV, respectively. The sliced tissue samples for
      electron microscopic examination were prepared for the morphologic observation of
      the viruses. Serum antibody to WNV or JEV was detected using indirect
      immunofluorescence assay (IFA), and the viral RNA was analyzed by RT-PCR method.
      RESULTS: WNV or JEV-caused CPE was characterized by cell fusion and cell
      shedding, respectively. There was no significant difference in the pathogenicity
      to suckling mice between WNV and JEV. The morphologic observation showed that the
      shape and size of the two virions were similar. WNV and JEV were found to have
      antigenic cross-reactivity. The viral RNA could be detected from both WNV and JEV
      samples with universal primer set, but only nucleoside fragments of corresponding
      virus could be amplified when specific primers were used. CONCLUSION: CPE in
      C6/36 cell and detection of the viral RNA should be useful in discrimination of
      WNV and JEV, and simultaneously examining the titers of serum antibodies against
      WNV and JEV may be helpful to diagnosis of infection with these agents.

PMID- 16415990
TI  - [Expression of tick-borne encephalitis virus prM-E protein in insect cells and
      studies on its antigenicity].
AB  - BACKGROUND: To express the prM-E protein in Sf9 cells, and lay a basis for
      further study on the function of the viral proteins and development of specific
      diagnostic reagents. METHODS: The recombinant prM-E protein of tick-borne
      encephalitis virus was expressed in insect cell Sf9 by RT-PCR amplification of
      prM-E gene, construction of donor plasmid of Bac-to-Bac baculovirus expression
      system, homologous recombination of donor plasmid with bacmid DNA at the site of
      Tn7 and transfection of insect cell Sf9. RESULTS: Recombinant subviral particles,
      about 30 nm in diameter, consisting of prM-E were observed by electron microscope
      in the supernatant of infected cells, which indicated that infected cells
      released virus-like particles (VLPs) into the culture medium. The results of
      Western-blot and the indirect immunofluorescence assay (IFA) showed that the
      recombinant proteins retained antigenic and conformational structures similar to
      those of native virus proteins. Using the recombinant prM-E as antigens to detect
      samples of patient sera by ELISA and IFA, all of 16 sera from patients with tick
      borne encephalitis were positive and all of 6 sera from other patients were
      negative. CONCLUSION: The prM-E protein expressed in insect cells retains good
      antigenicity.

PMID- 16415992
TI  - [Research on Culex tritaeniorhynchus and Culex pipiens quinquefasciatus
      intrathoracically infected with attenuated Japanese encephalitis virus SA14-14-2
      vaccine strain].
AB  - BACKGROUND: To determine if the attenuated Japanese encephalitis (JE) virus SA14
      14-2 vaccine strain interacts efficiently with Culex tritaeniorhynchus and Culex
      pipiens quinquefasciatus, and further to acquire a new knowledge of its
      characteristics and safety for human beings. METHODS: Laboratory colonies of the
      two species of mosquitoes were set up and were inoculated intrathoracically with
      the attenuated vaccine virus and wild JE virus (Nak), both of which were used
      with different dilution from 10(-1) to 10(-9). Subsequently, the virus titers in
      the mosquitoes were detected by the plaque assay. RESULTS: Inoculated with the
      vaccine strain, two species of mosquitoes were infected with the titers ranged
      from 10(0)-10(-3), and the maximum titers in Culex tritaeniorhynchus and Culex
      pipiens quinquefasciatus were 4.48 logPFU/ml and 5.63 logPFU/ml, respectively.
      Inoculated with wild JE virus, Culex pipiens quinquefasciatus was infected with
      titers ranged from 10(0)-10(-5), and the maximum titer in the mosquitoes was
      6.59; Culex tritaeniorhynchus was infected with titers ranged from 10(0)-10(-4)
      and the maximum titer was 5.74 logPFU/ml. CONCLUSION: By intrathoracic infection,
      the attenuated JE virus SA14-14-2 vaccine strain can replicate in both species of
      mosquitoes.

PMID- 16415993
TI  - [Detection of Sindbis virus-specific nucleic acid with SYBR GREEN I real time PCR
      assay].
AB  - BACKGROUND: To develop a rapid, specific and sensitive method for detecting
      Sindbis virus (SINV) with SYBR GREEN I real time PCR. METHODS: Total RNA of
      strains of Sindbis virus and a related virus were extracted and reverse
      transcribed to cDNAs. With the cDNAs as template, the SYBR GREEN I real time PCR
      assay was developed and optimized on ABI 7300 apparatus for specific-detection of
      Sindbis virus, and the sensitivity, specificity and reproducibility were
      evaluated. RESULTS: For the PCR, 55 degrees C was chosen as the optimal anneal
      temperature and 0.5 micromol/L as the optimal primer concentration. Using this
      method, all the selected SINV were detected as positive, while the results of
      control arboviruses such as Geta virus, Japanese encephalitis virus (JEV), Batai
      virus, Seadornavirus Orbiviruses and synthesized WEEV cDNA were negative. With
      this system, 0.1 PFU/ml SINV cDNA could be detected; The sensitivity of this
      assay was about 100 times higher than standard RT-PCR. All the results were
      reproducible within two compatible tests, and the stability of the detection
      system was very good. The test results of simulated infection human serum samples
      showed that human serum had no obvious interference with this system. With this
      system, 6 of 151 clinical samples with unknown fever or encephalitis were
      determined as positive. CONCLUSION: The developed SYBR GREEN I real time PCR
      assay for detecting Sindbis virus was highly sensitive, specific and showed a
      good reproducibility and stability. It is our belief that the present method can
      be further used in clinic sample to verify its stringency.

PMID- 16415994
TI  - [Receptor-binding ability of fragments 260-600 and 397-796 of SARS-associated
      coronavirus spike protein].
AB  - BACKGROUND: To investigate the interaction between the host cell and the
      truncated S fragments to identify the receptor-binding domain of the spike (S)
      protein of SARS-associated coronavirus (SARS-CoV). METHODS: Two different
      fragments S260-600 and S397-796 of the SARS-CoV S protein were expressed in
      Escherichia coli (E.coli) using a pET expression vector, respectively. The two
      recombinant proteins were separately verified by Western blot, purified by nickel
      affinity chromatography, and incubated with Vero cells, a susceptible cell line
      of SARS-CoV infection, for cell binding assay. After the sequential probing with
      sera from convalescent SARS-patients and FITC-labeled anti-human IgG, the cells
      were analyzed by flow cytometry. The NIH 3T3 cell, a non-permissive cell line of
      SARS-CoV infection, was used as controls. RESULTS: The recombinant proteins S260
      600 and S397-796 were efficiently expressed in an insoluble form in E.coli. The
      appropriate expression of the proteins was confirmed by Western blotting using
      both SARS patients' sera and anti-6 x histidine antibody. The flow cytometry
      results showed that the both proteins were able to bind Vero cells, but the
      binding ability of S260-600 was somewhat stronger than that of S397-796. In
      contrast, the S260-600 protein did not bind NIH3T3 cells. CONCLUSION: Both S260
      600 and S397-796 exhibited different receptor binding activity. The S260-600
      fragment probably contains the important receptor binding domain and could be a
      potential candidate for the development of SARS vaccine and anti-SARS
      therapeutics.

PMID- 16415996
TI  - [Antigenic and genetic study of hemagglutinin gene of influenza virus (H3N2)
      circulated in China in 2004].
AB  - BACKGROUND: To study the antigenic and genetic characteristics of influenza
      (H3N2) virus circulated in China in 2004. METHODS: Single-way and cross-way
      hemagglutination inhibition (HI) tests were firstly used to determine the
      reactivity with the reference serum of virus isolates. Based on the serological
      results, virus isolates were selected according to the different time and
      location in China in 2004. The HA1 domain of HA gene of those virus isolates were
      then sequenced in order to analyze the gene characterization. RESULTS: Single-way
      HI test results showed that 52.3% of isolates showed 4 folds or more HI titer
      difference compared to A/Fujian/411/2002 (H3N2) itself (international reference
      strain in 2004). Cross-way HI test results showed that the antigenic ratio was 4.
      The nucleic acid and amino acid sequence data of HA1 domain showed that the
      mutated virus appeared in early February of 2004, and became the dominant
      circulating strain gradually. There were four important mutant positions, they
      were 159 Y>F, 189 S>N, 145 K>N, 226 V>I, respectively. The results also indicated
      that the mutated viruses originated from southern China, then transmitted to
      northern China, according to the analysis of time and location distribution.
      CONCLUSION: The HA1 domain of HA gene of influenza virus (H3N2) isolated from
      2004 in China showed mutation and antigenic drift, and the mutated viruses were
      becoming the dominant circulating strain in China, and showed amino acid sequence
      difference compared to A/Fujian/411/2002 (H3N2) A/Wellington/1/2004 (H3N2), the
      vaccine components pronounced by WHO for 2004-2005 northern hemisphere and 2005
      southern hemisphere respectively, which suggested that further surveillance
      should be conducted to monitor the virus mutation in circulation.

PMID- 16415995
TI  - [Origin of internal genes of two strains of swine influenza A (H1N1) virus].
AB  - BACKGROUND: Through the analysis of internal genes of viruses to understand
      whether the internal genes of two strains of swine influenza A(H1N1) virus
      contain the gene segment deriving from avian influenza A viruses, and whether the
      reassortment of the internal genes occurred between swine H1N1 and swine H9N2
      viruses. METHODS: Viruses were passaged in embryonated hen eggs and virion RNA
      was extracted from allantoic fluids and reverse transcribed to synthesize cDNA.
      cDNA was amplified by PCR and the PCR product was purified with a purification
      kit. Afterwards, RNA sequence analysis was performed by dideoxynucleotide chain
      termination and a cloning method. Finally, phylogenetic analysis of the
      sequencing data was performed with MegAlign (version 1.03). RESULTS: All the six,
      but PB2 gene segment internal gene segments were the same between
      A/swine/Beijing/1/2002(H1N1) and A/Swine/Beijing/3/2002(H1N1) viruses. Whereas
      all the six internal gene segments in two trains of swine (H1N1) virus were
      similar to those of swine H1N1 viruses, but different from those of classical
      strain of swine (H1N1) virus. CONCLUSION: Two strains of Beijing swine H1N1
      influenza A virus were not reassortant, All the six internal gene segments were
      closely related to swine influenza A (H1N1) viruses.

PMID- 16415997
TI  - [Expression of HBV S and preS1 fusion gene in Pichia pastoris expression system].
AB  - BACKGROUND: To clone and express the ss1 recombinant gene containing S gene and
      preS1 (10-50 AA) gene in P. pastoris expression system. METHODS: The fusion gene
      ss1 containing the S (1-222 AA) gene and preS1 (10-50 AA) gene was constructed
      with PCR method. The fusion ss1 gene was cloned into the expression vector of
      pPIC3.5k. The linear vector DNA was transformed into the host cell of GS115 with
      electroporation method. After screening with G418, the product was induced to
      express with methanol and its antigenicity was analyzed. RESULTS: The molecular
      weight of expressed ss1 protein was about 30,000 dalton. The product was reactive
      to anti-HBs and anti-preS1 mAb. CONCLUSION: The fusion gene was efficiently
      expressed in P. pastoris expression system.The expressed products have the
      antigenicity of both S and preS1 protein.

PMID- 16415998
TI  - [Relationship among HPV16 infection and Expression of hTERT, p21waf1, Ki67 in
      cervical intraepithelial neoplasias and squamous cell carcinomas of cervix
      uteri].
AB  - BACKGROUND: To investigate the relationship among human papillomavirus (HPV)16
      infection and the expression of telomerase catalytic protein subunit (hTERT),
      tumor suppressor gene p21waf1, proliferation antigen Ki67 in cervical
      intraepithelial neoplasias (CIN) and squamous cell carcinomas (SCC) of cervix
      uteri and their significance. METHODS: Tissue microarray combined with in situ
      hybridization (ISH) and immunohistochemical staining (EliVision plus method) was
      used to detect the expression of HPV16 RNA, hTERT, Ki67 and p21waf1 proteins in
      the cervix uteri specimens from 130 subjects, including normal cervical tissue
      (n=26), CIN (n=46) and SCC (n=58). RESULTS: (1) The positive rate of HPV16
      hybridization signals and expression of hTERT, Ki67 in CINII-III, in situ
      carcinoma and invasive SCC were all significantly higher than in normal cervical
      tissue (P < 0.05 for all), and was also higher in SCC than in CIN (P < 0.05 for
      all). There was a significant difference among CIN I, II and III (P < 0.05 for
      all). (2) The positive expression of p21waf1 protein only in SCC was
      significantly lower than in normal cervical tissue (P < 0.05), but there was no
      significant differences among other groups (all P > 0.05). (3) The positive rate
      of HPV16 and the expression of Ki67 showed respectively positive being correlated
      with the expression of hTERT (P < 0.05, r=0.339; P < 0.05, r=0.398); HPV16, hTERT
      and Ki67 showed respectively negative correlation with the expression of p21waf1
      (P < 0.05, r=-0.337; P < 0.05, r=-0.248; P < 0.05, r=-0.446); There was no
      significant relation between HPV16 and Ki67 (P > 0.05). CONCLUSION: The results
      suggest that in tissues of CIN and SCC changes in hTERT, p21waf1 and Ki67
      expression may be associated with HPV16 infection and they interact with each
      other, which can influent the progression of CIN and carcinogenesis of SCC. These
      biomarkers may be analyzed comprehensively to reveal the detailed mechanism by
      which HPV16 participate in malignant transformation and to provide some
      informations on the diagnosis of patients with high risk for malignant
      progression. Tissue microarray is an efficient platform for high-throughput
      analysis of genes and their expression products in investigations.

PMID- 16415999
TI  - [Safety and tolerance study of single oral dose of adefovir dipivoxil tablets in
      healthy volunteers].
AB  - BACKGROUND: To assess the safety and tolerance of adefovir dipivoxil tablet in
      Chinese healthy volunteers. METHODS: Totally 42 healthy volunteers were enrolled
      in the study, 21 were female and 21 were male and their age ranged from 19 to 26
      years. The subjects were randomly divided into 5, 10, 20, 40 and 60 mg dose
      groups (6-10 subjects in each group) based on sex and weight, beginning with the
      5 mg dose-group. Clinical symptoms, vital signs, electrocardiogram, routine blood
      test, routine urine test, prothrombin time and blood biochemical tests were
      recorded and evaluated. RESULTS: No significant changes were found in clinical
      symptoms, vital signs and laboratory tests after dosing, except slight elevations
      of alanine aminotransferase in 2 subjects and bilirubin in 6 subjects observed
      and some gastrointestinal symptoms such as nausea and diarrhea found in 3
      subjects, but the frequency and severity of all the adverse reactions were not
      found to be related to the dosages. CONCLUSION: The results showed that single
      oral dose of adefovir dipivoxil 60 mg or less was safe and tolerable.

PMID- 16416000
TI  - [Study on treatment effectiveness and safety in children with chronic hepatitis B
      or C using bicyclo tablets].
AB  - BACKGROUND: To evaluate treatment effectiveness and safety of bicyclo tablets in
      children with chronic hepatitis B or C. METHODS: A randomized controlled trial
      was conducted in 148 children with chronic hepatitis B or C for evaluating
      safety, tolerability, and efficacy of treatment with bicyclo tablets or Hugan
      tablets. Children in therapy group were treated with bicyclo tablets and control
      group treated with Hugan tablets. RESULTS: (1) ALT and AST level decreased more
      prominently in therapy group than in control group (P<0.01). (2) Bicyclo was more
      effective than Hugan tablets (P<0.01). (3) Symptoms were ameliorated more
      prominently in bicyclo group than in control group (P<0.01). (4) Both groups had
      no significant adverse events. CONCLUSION: Satisfactory therapeutic effect and
      safety were obtained with bicyclo tablets in children with chronic hepatitis B or
      C.

PMID- 16416002
TI  - [Sequential analyses of circulating HBV specific T helper cell response in
      chronic hepatitis B patients receiving antiviral treatment].
AB  - BACKGROUND: To investigate the frequency of circulating HBV specific T helper
      cell and evaluate its association with serum levels of HBV DNA before and during
      lamivudine treatment in patients with chronic hepatitis B. METHODS: The frequency
      of circulating HBV specific T helper cells in response to HBcAg in 25 chronic HBV
      infected patients was determined by Elispot assay; serum HBV DNA was quantitated
      by real-time PCR. RESULTS: The frequency of HBV specific T helper cell before
      antiviral treatment (47.30 +/- 25.50 SFCs /1 x 10(6) PBMC) was significantly
      higher than that at the third month of therapy (23.10 +/- 18.45 SFCs /1 x 10(6)
      PBMC, P < 0.05). All 8 patients observed dynamically had decreased frequency of
      HBV specific T helper cell at the third month of therapy; six patients with serum
      HBV DNA level reduced had higher frequency of HBV specific T helper cell before
      treatment than 2 patients without serum HBV DNA level decrease. CONCLUSION: HBV
      specific T helper cell response at the time of hepatitis flare in chronic
      hepatitis B patients was significantly augmented compared to that at the time of
      catabasis.

PMID- 16416001
TI  - [A clinical study on CD178 positive T lymphocyte in hemorrhagic fever with renal
      syndrome].
AB  - BACKGROUND: To further probe into the role of CD178 in the pathogenesis of
      hemorrhagic fever with renal syndrome (HFRS). METHODS: The expression of CD178
      and HLA-DR on T cell subsets in peripheral blood of patients with HFRS and their
      dynamic changes were detected by Flow cytometry. RESULTS: CD4+ CD178+ and CD8+
      CD178+ T lymphocytes both in fever and polyuria phases were significantly higher
      than those in normal controls, while there was no significant difference between
      the both phases of HFRS (P > 0.05). CD178 expression on CD4+ HLA-DR+ and CD8+ HLA
      DR+ T lymphocytes were significantly higher than those in normal controls (P <
      0.05, P < 0.01, P < 0.001, P < 0.001), while there was no significant difference
      between CD4+ HLA-DR+ and CD8+ HLA-DR+ T lymphocytes (P > 0.05). CONCLUSION: CD178
      was expressed on both CD4+ and CD8+ T cell subsets, but mainly on CD8+ T cell
      subsets both in early stage and in later stage in the pathogenesis of HFRS.
      Cytotoxic T lymphocyte (CTL) might kill target cells infected by hantavirus (HV)
      and eliminate HV via cell apoptosis mediated by CD178 in early stage of HFRS. In
      later stage of HFRS, CD178 might reduce antigen-specific T lymphocytes by
      activation induced cell death (AICD) and help to maintain the homeostasis of
      immune system.

PMID- 16416003
TI  - [Dynamic expression of hepatitis B virus covalently closed circular DNA in 2.2.15
      cell].
AB  - BACKGROUND: To determine the presence of covalently closed circular DNA (cccDNA),
      and to investigate the expression kinetics of HBV DNA, HBsAg and HBeAg in 2.2.15
      cell. METHODS: HBV cccDNA was assessed by polymerase chain reaction, HBV DNA was
      measured by Taqman quantitative PCR and HBsAg and HBeAg was measured by EIA.
      RESULTS: HBV cccDNA was found in both intracellular and extracellular space.
      There was a good correlation between HBsAg, HBeAg and HBV DNA in the supernatant
      of 2.2.15 cell (r= 0.833, P < 0.05 and r= 0.939, P < 0.01 for HBsAg and HBeAg,
      respectively), whereas there was no significant correlation between intracellular
      HBV DNA levels and virus antigen levels (r= 0.024, P= 0.955 and r= 0.177; P=
      0.625 for HBsAg and HBeAg, respectively). CONCLUSION: HBV cccDNA was detectable
      in the culture medium and intracellularly in 2.2.15 cells, and these data
      provided an indication of HBV replication in 2.2.15 cell.

PMID- 16416004
TI  - [Antiviral therapy of chronic hepatitis B patients resistant to lamivudine].
AB  - BACKGROUND: To evaluate the efficacy of alpha-2b interferon alone or combined
      with alpha1-thymosin in treatment of patients with chronic hepatitis B (CHB)
      resistant to lamivudine. METHODS: Sixty six patients with CHB resistant to
      lamivudine were enrolled and randomized into treatment group A, treatment group B
      and control group. In the treatment group A 26 cases, after giving interferon
      alpha alone for 1 month, lamivudine was withdrawn and continuously treated with
      interferon-alpha for 5 months. In the treatment group B 10 cases, after treatment
      with interferon-alpha and thymosin-alpha1 for 1 month, lamivudine was withdrawn
      and continuously treated with interferon-alpha and thymosin-alpha1 for 5 months.
      In control group (30 cases), after lamivudine was directly withdrawn, no anti
      virus drug was given. Hepatic function tests and serum virological index were
      detected at regular intervals in all patients. RESULTS: Normalization rate of
      hepatic function, HBV DNA seroconversion rate and HBeAg/HBeAb seroconversion rate
      in two treatment groups were significantly higher than those in control group.
      CONCLUSION: The study suggested that interferon-alpha alone or combined with
      thymosin-alpha1 in treatment of patients with chronic hepatitis B resistant to
      lamivudine showed a beneficial effect.

PMID- 16416005
TI  - Suppression of glucosylceramide synthase by RNA interference reverses multidrug
      resistance in human breast cancer cells.
AB  - Glucosylceramide synthase (GCS), the enzyme that converts ceramide to
      glucosylceramide, induce multidrug resistance (MDR) in cancer cells. Recently,
      RNA interference (RNAi) is a powerful strategy for gene therapy by introducing
      double-stranded RNA and leading to the sequence-specific destruction. We have
      designed two different short hairpin RNAs (shRNAs) targeting GCS and introduced
      them into adriamycin- resistant human breast cancer cells (MCF-7/AdrR cells) to
      inhibit GCS expression. The results demonstrated that the shRNAs targeting GCS
      decreased GCS mRNA, abolished GCS protein levels and restored the sensitivity of
      MCF-7/AdrR cells to several antineoplastic drugs. This study revealed that this
      approach can reverse MDR effectively and it may be applicable to cancer patients
      as a specific means to restore the sensitivity to chemotherapy.

PMID- 16416007
TI  - Silencing of DMBT1 in neuroblastoma cell lines is not due to methylation of CCWGG
      motifs on its promoter.
AB  - DMBT1 is one of the putative suppressor genes on 10q25-qter, which frequently
      lacks expression in many different kind of tumors, such as glioblastoma, and
      lung, esophageal and colorectal cancer. However, little is known about the
      reasons for this lack of expression in neoplasia. In a previous report, our group
      demonstrated how MC-IXC, a neuroblastoma cell line which lacked DMBT1 expression,
      restored it after a 5-Aza-2'-deoxycitidine treatment. So, we wondered whether
      DMBT1 aberrant promoter methylation could be responsible for DMBT1 silencing in
      several tumor cell lines, in spite of the fact that there is no CpG island near
      the 5' end of the gene. We studied the possibility that methylation in CCWGG
      sequences of the DMBT1 promoter (where "W" means "A" or "T") is able to silence
      the gene, as had previously been reported for TP53 in leukemia. We digested
      genomic DNA by the methylation sensitive restriction enzyme EcoR II (C|CWGG), and
      made two PCRs to amplify the three CCWGG domains placed in the 1 kb upstream
      DMBT1 5' end. After the PCRs, we could not find correlation between methylation
      in CCWGG domains and DMBT1 lack of expression. A positive regulator of DMBT1
      might be silenced by aberrant methylation.

PMID- 16416006
TI  - Prognostic significance of tyrosinase mRNA detected by nested RT-PCR in patients
      with malignant melanoma.
AB  - The aim of this study was to evaluate the role of tyrosinase mRNA appearance in
      blood of malignant melanoma (MM) patients, especially with advanced stages, for
      predicting the disease progression, and consequently the survival. The tyrosinase
      mRNA was measured by nested RT-PCR in peripheral venous blood samples obtained
      from 86 patients (53 male and 33 female) with mainly stage III and IV MM. The
      data were analyzed using standard methods for survival analysis and logistic
      regression. Tyrosinase was negative in the MM patients with the disease stage I
      or II, positive tyrosinase was in 11/50 patients with stage III and in 5/22
      patients with stage IV. Systemic metastases developed in 14/16 patients with
      positive tyrosinase and in 41/70 with negative tyrosinase. The 3-year survival
      was 8% and 28% among the patients with positive and the patients with negative
      tyrosinase, respectively. The log rank test showed statistically significant
      better survival of tyrosinase negative patients when compared to tyrosinase
      positive patients (p=0.039). Multivariate analysis using logistic regression
      indicated tyrosinase to be a statistically significant prognostic factor for the
      survival of MM patients after controlling for Breslow and ulceration values
      (p=0.006). Positive tyrosinase in peripheral venous blood is statistically
      significant, and more importantly independent negative predictor of survival.

PMID- 16416008
TI  - Current trends and perspectives in nutrition and cancer prevention.
AB  - There is an increasing evidence that dietary phytochemicals may play important
      roles as chemopreventive or chemotherapeutic agents in prevention of many
      diseases, including tumors. The purpose of this study was to examine
      antimutagenic effects and effect on the immune response of representative series
      of substances which commonly occur in human diet. Using the Ames bacterial
      mutagenicity test and in vivo chemiluminescence test, we investigated
      antigenotoxic and immunomodulatory effects of juices and vegetable homogenates
      (carrot + cauliflower, cauliflower, red cabbage, broccoli, onion, garlic) on the
      genotoxicity of AFB1 and pyrolysates of aminoacids. Using the Ames test and in
      vivo micronucleus, the chemiluminescence test, the blastic transformation test
      and the comet assay we examined antimutagenic effects of chemically identified
      chemoprotective substances in the pure form (resveratrol, diallylsulphide,
      phenethyl isothiocyanate, ellagic acid, epigallocatechin gallate, genistein and
      curcumin) on mutagenicity induced by three reference mutagens: aflatoxin B1
      (AFB1), 2-amino-3-metylimidazo[4,5,-f] chinolin (IQ) and N-nitroso- N-metylurea
      (MNU) and effect of phytochemicals on the immunosuppression caused by these
      mutagens. All complete vegetable homogenates and substances of plant origin
      tested, showed a clear antimutagenic and immunomodulatory activities on
      mutagenicity and immunosuppression induced by reference mutagens. Only in the
      Ames test the effect of some phytochemicals against direct mutagen MNU was lower
      compared to indirect mutagens AFB1 and IQ. Similarly, resveratrol and
      epigallocatechin gallate had no inhibitory effect on mutagenicity MNU in the Ames
      test.

PMID- 16416009
TI  - The significance of soluble CD138 in diagnosis of monoclonal gammopathies.
AB  - Report is summary of the results of study designed to ascertain the significance
      of soluble CD138 (sCD138) assessment in patients with different monoclonal
      gammopathies. Previous studies have shown that sCD138 is shed from the surface of
      myeloma cells into serum and that this marker is a new independent prognostic
      parameter in multiple myeloma. In presented study was evaluated serum sCD138
      level in 14 patients with monoclonal gammopathy of undetermined significance
      (MGUS) and in 17 patients with multiple myeloma (MM), all MM patients were
      treated by high-dose chemotherapy regimen with subsequent autologous
      transplantation of peripheral blood stem cells. To determine the sCD138 level we
      used a rapid and simple ELISA procedure. The mean serum sCD138 level of patients
      with MGUS was 32 ng/ml (range: 5-128). Soluble CD138 levels were elevated in the
      sera of 10 out of 17 (59%) multiple myeloma patients, the mean baseline sCD138
      concentration was 1542 ng/ml (range: 10-17300). In spite of small number of
      patients the difference between MGUS and MM group was highly statistically
      significant (p<0.001). Multiple myeloma patients with high level of sCD138 at
      diagnosis (cut-off value: 500 ng/ml) had worse prognosis despite of good response
      to chemotherapy in some of them (p=0.029). It seems that determination of sCD138
      can be recommended as a helpful and reliable marker for differential diagnosis as
      well as prognosis of monoclonal gammopathies.

PMID- 16416010
TI  - The addition of induction chemotherapy with etoposide, ifosfamide, and cisplatin
      failed to improve therapeutic outcome of concurrent chemoradiotherapy in patients
      with locally advanced non-small cell lung cancer -- single institution
      retrospective analysis.
AB  - Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally
      advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be
      determined. We retrospectively compared the treatment results of induction
      chemotherapy followed by concurrent CRT (induction group, 32 patients) with those
      of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage
      IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy
      (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed
      by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the
      same concurrent CRT was administered in concurrent group. Clinicopathologic
      characteristics including age, weight loss, histologic types, and clinical stage
      did not show significant differences between two groups except for a higher
      proportion of patients with ECOG performance status 2 in concurrent group (3% vs.
      27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related
      death from tracheoesophageal fistula in induction group. The response rates after
      concurrent CRT were 41% for induction group and 54% for concurrent group, which
      showed no significant difference (p=0.560). With median follow-up of 13 (1-92)
      months, there was a trend toward an advantage for concurrent group in median
      progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival
      (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than
      10% weight loss within 6 months was significantly associated with poor survival
      (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent
      CRT did not show any advantage over concurrent CRT alone in locally advanced
      NSCLC.

PMID- 16416011
TI  - The relevance of the corticographic median nerve somatosensory evoked potentials
      (SEPs) phase reversal in the surgical treatment of brain tumors in central
      cortex.
AB  - Tumors of the central brain cortex change the original anatomy of this important
      area and so an intraoperative localization of the perirolandic structures is
      crucial in decision concerning the way and the extent of tumor resection. The
      phase reversal of median nerve SEPs is an essential tool for neurosurgical
      procedures in and around the perirolandic gyri. This study examines the relevance
      of the method in a group of 62 patients having surgery of tumors in and around
      the central region. A success rate in obtaining the SEP phase reversal was 94%.
      In all groups of patients the complete resection of tumor was achieved in 58% ,
      subtotal resection in 19% and partial or biopsy only in 23%. The long term
      impairment of neurological status was observed in 6% of patients. Compared to the
      recently published studies our results are acceptable both in completeness of
      tumor resection and relatively low ratio of impaired postoperative neurological
      deficit despite the fact, that in the majority of patients the phase reversal
      mapping was the only method guiding the surgical procedure. Our study supports
      the crucial role of the central cortex mapping using the SEP phase reversal
      method in the surgery for the tumors of the primary sensorimotor cortex.

PMID- 16416012
TI  - P53 correlates positively with VEGF in preoperative sera of colorectal cancer
      patients.
AB  - Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type
      P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant
      P53 upregulates it. Therefore, we aimed at uncovering relations between
      preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients.
      Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers
      were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not
      correlate with VEGF in the whole group of CRC patients. However, P53 associated
      with VEGF in case of colorectal cancer patients, whose serum values of VEGF were
      higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a
      positive correlation between P53 and VEGF{H} in subsets of poorly differentiated
      (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients
      (p<0.004) without analogous relation in moderately differentiated (G2) tumors,
      node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively
      correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4
      (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive
      correlation between serum P53 and VEGF points at mutation of P53 and is a highly
      probable sign of poor prognosis in colorectal cancer. For now it can not be
      excluded that the binary analysis of serum P53 and VEGF could help select CRC
      patients endangered by rapid growth and lymph node metastases.

PMID- 16416013
TI  - HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a
      population-based case-control study in Slovakia.
AB  - Breast cancer belongs to the most frequent types of cancer affecting women and it
      occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak
      republic. One of the most important factors in connection with cancer genesis
      refers to changes in specific genes. HER-2 proto-oncogene belongs to low
      penetrating genes, which increase susceptibility to breast cancer genesis.
      Clinical studies demonstrated an association between polymorphism at codon 655 of
      this gene and increased risk for breast cancer development. The aim of this case
      control based prospective study was to determine the distribution of HER-2
      genotype and its association with risk factors of breast cancer in the population
      of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP
      method. The DNA was isolated from white blood cell nuclei. The frequency of Val
      allele in the cancer group was 29.79% and was higher than in the control group
      15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was
      identified in 46.81% of patients in the case group and in 28.33% in healthy
      individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67,
      respectively (p<0.01). The risk of breast cancer development for carriers of one
      valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers
      of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele
      carriers was higher in multiparas (OR=2.90), among women with positive family
      history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5).
      Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val
      allele carriers (OR=0.3). In conclusion, this study revealed relatively high
      frequency of the Val allele among the women population of the Slovak republic.
      Ile655Val polymorphism of HER-2 gene was associated with a statistically
      significantly increased risk of breast cancer all above in homozygotes for Val
      allele.

PMID- 16416014
TI  - Reorganization of actin in K-562 and HL-60 cells treated with taxol.
AB  - Influence of taxol, microtubular poison, has been studied on distribution of
      actin. K-562 and HL-60 cells were treated with taxol in a range of concentrations
      0.02-10 microM for 72 hours. The reorganization of F-actin was dependent on its
      dose. Phalloidin conjugated to TRITC was used to evaluate actin distribution by
      classical fluorescence and confocal microscopy. Actin was visualized at
      ultrastructural level by using a postembedding streptavidin-gold method. The
      treatment of K-562 and HL-60 cells with 2-10 microM of taxol resulted in an
      increase of F- actin in the cytoplasm, with intense labeling as a ring close to
      surface of the cell. In HL-60 cells a concentration of F- actin at the site of
      apoptotic bodies was often observed. Immunogold labeling of actin was localized
      in the nuclei and cytoplasm in control cells and cells treated with all doses of
      taxol. At higher doses, compaction of chromatin in the nucleus with strong actin
      labeling was observed. These observations at the ultrastructural level suggest
      actin involvement in chromatin reorganization during the process of apoptosis.
      The present study demonstrated a dose dependent reorganization of actin after
      treatment with taxol.

PMID- 16416015
TI  - Echocardiographic evaluation of early and chronic cardiotoxicity in adult
      patients treated for Hodgkin's disease with ABVD regimen.
AB  - The prospective study was conducted to determine whether standard regimen ABVD
      used in the treatment of Hodgkin's disease is accompanied by the presence of
      early and chronic myocardial impairment. The study comprised 52 patients (30 male
      and 22 female) aged 34+/-15 years (range 18-71; median 30) with Hodgkin's disease
      and the control group with 40 healthy volunteers (21 male and 19 female) aged
      40+/-8 years (range 20-70; median 38). The maximal administered cumulative dose
      (CD) of doxorubicin was 297+/-50 mg/m2 (range 150-450; median 300). Radiotherapy
      of the mediastinum was delivered to 27 (52%) patients with a mean dose 41+/-4 Gy
      (range 30-46; median 42). Echocardiography was performed at baseline and before
      each course of chemotherapy. The control examination was done at one month after
      the treatment and after one year. The stress echocardiography was performed at
      one-year control. Significant change of ejection fraction (EF) during the
      treatment was observed only in 10 (18%) patients (7 male/3 female) aged 29+/-13
      years (range 18-56; median 22). The mean toxic CD of doxorubicin was 170+/-33
      mg/m2 (range 100-200; median 175) and the mean time of the onset EF decline was
      13.3+/-3 weeks (range 8-16; median 14). These changes were asymptomatic, and all
      patients completed the treatment successfully. Four patients (8%) demonstrated
      significant asymptomatic decline of EF after the chemotherapy. When compared the
      value of EF after one-year examination, a stable significant decline of EF in the
      sub-group with early toxicity was found. Despite a difference in the rest EF, the
      exercise increment of EF did not reveal any significant difference among tested
      groups and the contractile reserve of the left ventricle in patients was not
      impaired. The present data shows that the treatment of Hodgkin's disease with the
      standard ABVD regimen is accompanied with mild early and chronic asymptomatic
      changes of the left ventricular function. These changes were not reversible
      during one-year follow-up.

PMID- 16416016
TI  - Risk of malignant tumors in first-degree relatives of patients with
      differentiated thyroid cancer -- a hospital based study.
AB  - In presented study the risk of incidence of familial differentiated thyroid
      cancer as well as the risk of other malignant tumors in families of DTC patients
      was evaluated. 999 patients with differentiated thyroid cancer and 825 persons
      without any history of malignant disease were evaluated on the occurrence of
      malignant neoplasm within their families. Information about 6614 first degree
      relatives of DTC index patients and 4939 first degree relatives of control
      persons were recorded. The incidence of cancers at various sites was compared
      between first-degree relatives of index patients and control persons and odds
      ratio with 95% confidence intervals (CI) were calculated for thyroid cancer and
      other cancer sites. Within 999 families of thyroid cancer index patients 23
      families with more than one case of DTC were found. The risk of the development
      of thyroid cancer in the first degree was 6 (95% CI 1.8-19) times greater in the
      index group than in the control group. No increased risk for development of other
      malignancies was observed. Results of our study confirm previous reports of
      increased risk of thyroid cancer in first-degree relatives of differentiated
      thyroid cancer patients. However, the relatively small number of first-degree
      relatives affected with thyroid cancer (24/6614) does not justify at present any
      screening in the first-degree relatives of patients affected with differentiated
      thyroid cancer. Simultaneously, no increased risk of other malignant neoplasm was
      observed in the differentiated cancer families.

PMID- 16416017
TI  - Comparison of NAT1, NAT2 and GSTT2-2 activities in normal and neoplastic human
      breast tissues.
AB  - In this study, arylamine N-acetyltransferases, NATs (E.C.2.3.1.5) and glutathione
      S-transferase-T2-2, GSTT2-2 (E.C.2.5.1.18) enzyme activities in the breast tumor
      and surrounding tumor-free tissues of 22 female breast cancer patients with
      infiltrating ductal carcinoma were measured. The possible impacts of grade of
      malignancy, chemotherapy treatment, estrogen receptor status and menopausal
      status on all enzyme activities were evaluated. The results showed that, both
      NAT2 and GSTT2-2 display significant differences between tumor and tumor-free
      breast tissues, while no difference was observed in NAT1. Grade of malignancy
      seems to be positively associated with NAT1 and negatively associated with GSTT2
      2. Though, both NAT2 and GSTT2-2 have increased mean tumor activities, the grade
      of malignancy, chemotherapy status, menopausal status or estrogen receptor status
      are not correlated statistically.

PMID- 16416018
TI  - Some biological actions of PEG-conjugated RNase A oligomers.
AB  - Previously we have shown that monomeric RNase A has no significant biological
      activity, whereas its oligomers (dimer to tetramer) prepared by lyophilizing from
      50% acetic acid solutions, show remarkable aspermatogenic and antitumor
      activities. Furthermore, conjugates prepared by chemical binding of native RNase
      A to polyethylene glycol (PEG) have shown a significant aspermatogenic and
      antitumor activities. In this work we show that the chemical conjugation of PEG
      to the RNase A C-dimer, and to the two RNase A trimers (NC-trimer and C- trimer)
      decreases the aspermatogenic activity of the oligomers while increasing their
      inhibitory activity on the growth of the human UB900518 amelanotic melanoma
      transplanted in athymic nude mice. Moreover, the PEG-conjugated RNaseA oligomers
      are devoid, like the free oligomers, of any embryotoxic activity.

PMID- 16416019
TI  - Detecting natural selection at the molecular level: a reexamination of some
      "classic" examples of adaptive evolution.
AB  - An important criterion used to detect adaptive evolution in DNA sequence data is
      omega(i) > 1, where omega(i) is the ratio of nonsynonymous to synonymous
      substitution rates in lineage i. However, the evaluation of multiple omega(i)
      within a phylogenetic tree can easily inflate the statistical type I error rate.
      We developed two rigorous methods of analysis that avoid this and other potential
      pitfalls. We applied these methods to four published examples of adaptive
      evolution. One case was strongly supported by our reanalysis (abalone sperm
      lysin), and one was weakly supported (baboon alpha-globin), but two examples
      (primate lysozyme and Antarctic fish beta-globin) did not show significant
      evidence of adaptive evolution. Our first method is a "bottom-up" hierarchical
      maximum likelihood approach, which (1) tests for significant heterogeneity in
      omega across the phylogeny, (2) locates its source using a sequence of planned
      comparisons, and (3) tests homogeneous groups of omega for omega > 1, using a
      modified level of significance that incorporates the pretesting. The second
      method is a "top-down" log-linear analysis based on estimates of nonsynonymous
      and synonymous substitutions in pairs of lineages. The log-linear test is applied
      to pairs of lineages joined at progressively deeper nodes. For each pair, the
      analysis simultaneously tests for adaptive evolution (omega > 1), a shift in
      natural selection (omega1 does not = omega2), and unequal evolution rate (the
      relative rate test). In both tests, we emphasized that the criterion omega1 not
      equal omega2 is an important additional indicator of a phylogenetic shift in the
      balance between natural selection and genetic drift between two related lineages.

PMID- 16416020
TI  - The mutually exclusive flip and flop exons of AMPA receptor genes were derived
      from an intragenic duplication in the vertebrate lineage.
AB  - The incomplete correlation between the organismal complexities and the number of
      genes among eukaryotic organisms can be partially explained by multiple protein
      products of a gene created by alternative splicing. One type of alternative
      splicing involves alternative selection of mutually exclusive exons and creates
      protein products with substitution of one segment of the amino acid sequence for
      another. To elucidate the evolution of the mutually exclusive 115-bp exons,
      designated flip and flop, of vertebrate AMPA receptor genes, the gene structures
      of chordate (tunicate, cephalochordate, and vertebrate) and protostome
      (Drosophila and Caenorhabditis elegans) AMPA receptor subunits were compared.
      Phylogenetic analysis supports that the vertebrate flip and flop exons evolved
      from a common sequence. Flip and flop exons exist in all vertebrate AMPA receptor
      genes but only one 115-bp exon is present in the genes of tunicates and
      cephalochordates, suggesting that the exon duplication event occurred at the
      ancestral vertebrate AMPA receptor gene after the separation of vertebrates from
      primitive chordates. The structures of animal AMPA receptor genes also suggest
      that an intron insertion to separate the primordial flip/flop exon from the M4
      coding exon occurred before the exon duplication event and probably at the
      chordate lineage.

PMID- 16416021
TI  - The effect of the enkephalin DADLE on transcription does not depend on opioid
      receptors.
AB  - [D-Ala(2),D-Leu(5)] enkephalin (DADLE) is a synthetic peptide capable of inducing
      a hibernation-like state in mammals in vivo and in cultured cells in vitro. The
      effects of DADLE seem to be due to its binding to opioid receptors; however, it
      inhibits the growth of LNCaP cells, devoid of opioid receptors. We have
      investigated the effects of DADLE on this cell line using transmission electron
      microscopy, immunocytochemistry and cytometry, in order to elucidate the general
      mechanism(s) by which this enkephalin affects cell metabolism. We demonstrated
      that, similar to cell lines provided with opioid receptors, in LNCaP cells DADLE
      induces structural modifications of cytoplasmic and nuclear constituents, as well
      as a decrease in transcription and proliferation. However, DADLE does not provoke
      an increase in apoptotic or necrotic cell fraction, and, after removing the
      enkephalin from the culture medium, all effects disappear. We also demonstrated
      that DADLE molecules enter the cytoplasm and the nucleus of LNCaP cells, mostly
      binding to perichromatin fibrils and dense fibrillar component, where
      transcription and early splicing of pre-mRNAs and pre-rRNAs occur. In conclusion,
      our data demonstrate that the effect of DADLE on transcription and on cultured
      cells does not depend on opioid receptors. DADLE can, therefore, be envisaged as
      an extremely promising molecule to be used for inducing a reversible
      hypometabolic state in various cultured cells, without provoking cell damage or
      death.

PMID- 16416022
TI  - Sphingosine-1-phosphate signaling regulates lamellipodia localization of
      cortactin complexes in endothelial cells.
AB  - Sphingosine-1-phosphate (S1P), a serum-borne lipid mediator, was demonstrated to
      be a potent chemoattractant of endothelial cells. It was recently shown that the
      colocalization of cortactin and actin related protein 2/3 (Arp2/3) in the
      lamellipodia is critical to S1P-induced endothelial chemotaxis. In this report,
      we describe that S1P-stimulated cortactin translocation to the cell periphery to
      form lamellipodia is specifically mediated by the endothelial S1P1 G-protein
      coupled receptor, and is regulated by G(i)-mediated Akt-dependent S1P1 receptor
      phosphorylation and Cdc42/Rac activation pathways. In contrast to Src-dependent
      fibroblast growth factor-induced cortactin translocation, tyrosine
      phosphorylation cascades are not required for S1P-mediated lamellipodia formation
      and chemotaxis. Furthermore, we also demonstrate that S1P signaling, via the
      G(i)/Akt/S1P1 phosphorylation/Rac pathway, regulates the cortactin-Arp2/3 complex
      formation, which ultimately results in membrane ruffling, formation of the
      lamellipodia and endothelial migration.

PMID- 16416023
TI  - Protein kinase C-mediated endothelial barrier regulation is caveolin-1-dependent.
AB  - Protein kinase C (PKC) is activated in response to various inflammatory mediators
      and contributes significantly to the endothelial barrier breakdown. However, the
      mechanisms underlying PKC-mediated permeability regulation are not well
      understood. We prepared microvascular myocardial endothelial cells from both wild
      type (WT) and caveolin-1-deficient mice. Activation of PKC by phorbol myristate
      acetate (PMA) (100 nM) for 30 min induced intercellular gap formation and
      fragmentation of VE-cadherin immunoreactivity in WT but not in caveolin-1
      deficient monolayers. To test the effect of PKC activation on VE-cadherin
      mediated adhesion, we allowed VE-cadherin-coated microbeads to bind to the
      endothelial cell surface and probed their adhesion by laser tweezers. PMA
      significantly reduced bead binding to 78+/-6% of controls in WT endothelial cells
      without any effect in caveolin-1-deficient cells. In WT cells, PMA caused an 86+/
      18% increase in FITC-dextran permeability whereas no increase in permeability was
      observed in caveolin-1-deficient monolayers. Inhibition of PKC by staurosporine
      (50 nM, 30 min) did not affect barrier functions in both WT and caveolin-1
      deficient MyEnd cells. Theses data indicate that PKC activation reduces
      endothelial barrier functions at least in part by the reduction of VE-cadherin
      mediated adhesion and demonstrate that PKC-mediated permeability regulation
      depends on caveolin-1.

PMID- 16416024
TI  - Fibroblast spreading induced by connective tissue stretch involves intracellular
      redistribution of alpha- and beta-actin.
AB  - Mechanical stretching of connective tissue occurs with normal movement and
      postural changes, as well as treatments including physical therapy, massage and
      acupuncture. Connective tissue fibroblasts were recently shown to respond
      actively to short-term mechanical stretch (minutes to hours) with reversible
      cytoskeletal remodeling, characterized by extensive cell spreading and
      lamellipodia formation. In this study, we have examined the effect of tissue
      stretch on the distribution of alpha- and beta-actin in subcutaneous tissue
      fibroblasts ex vivo. Normal fibroblasts uniformly exhibited alpha-smooth muscle
      actin (alpha-SMA) immunoreactivity. Unlike cultured fibroblasts and smooth muscle
      cells, alpha-SMA in these fibroblasts was not in F-actin form (indicated by lack
      of phalloidin co-localization) nor was it organized into distinct stress fibers.
      The lack of stress fibers and fibronexus was confirmed by electron microscopy,
      indicating that these cells were not myofibroblasts. In unstretched tissue, the
      pattern of alpha-actin was diffuse and granular. With tissue stretch (30 min),
      alpha-actin formed a star-shaped pattern centered on the nucleus, while beta
      actin extended throughout the cytoplasm including lamellipodia and cell cortex.
      This dual response pattern of alpha- and beta-actin may be an important component
      of cellular mechanotransduction mechanisms relevant to physiologic and
      therapeutic mechanical forces applied to connective tissue.

PMID- 16416025
TI  - Clostridial neurotoxins: structure-function led design of new therapeutics.
AB  - The neurotoxins produced by various species of Clostridia are the causative
      agents of botulism and tetanus. The ability of the toxins, specifically those of
      the botulinum neurotoxin family, to disrupt neurotransmission has been exploited
      for use in several medical indications and now represents the therapeutic option
      of choice in a number of cases. Clostridial neurotoxins have been discovered to
      have a multi-domain structure that is shared between the various proteins of the
      family, and it has also been determined that each domain contributes a specific
      role to the holotoxin. The extensive use of recombinant expression approaches,
      along with solution of multiple crystallographic structures of individual
      domains, has enabled researchers to explore structurefunction relationships of
      the toxin domains more closely. These advances have facilitated a greater
      understanding of the potential use of individual domains for a wide variety of
      purposes, including the development of new therapeutics.

PMID- 16416026
TI  - Heterogeneous bioenergetic behaviour of subsarcolemmal and intermyofibrillar
      mitochondria in fed and fasted rats.
AB  - This study was designed to examine energetic behaviour of skeletal muscle
      subsarcolemmal and intermyofibrillar mitochondrial populations. The data show
      that subsarcolemmal mitochondria exhibited a lower degree of coupling and
      efficiency than intermyofibrillar ones, and can therefore be considered less
      efficient at producing ATP. In addition, subsarcolemmal mitochondria showed an
      increased sensitivity to palmitate-induced uncoupling, in line with high adenine
      nucleotide translocator content and decreased oxidative damage. We then
      determined the effect of 24 h fasting on energetic characteristics of skeletal
      muscle mitochondrial populations. We found that fasting enhanced proton leak and
      decreased the degree of coupling and efficiency, both in the absence and in the
      presence of palmitate only in subsarcolemmal mitochondria. Moreover, this
      mitochondrial population showed lower oxidative damage, probably due to a counter
      regulatory mechanism mediated by uncoupling protein 3. Subsarcolemmal and
      intermyofibrillar mitochondria appear to exhibit different energetic
      characteristics and can be differently affected by physiological stimuli.

PMID- 16416027
TI  - Intra-vascular glucocorticoid metabolism as a modulator of vascular structure and
      function.
AB  - The ability of glucocorticoids to directly alter arterial function, structure and
      the inflammatory response to vascular injury may contribute to their well
      established link with the development of cardiovascular disease. Recent studies
      have emphasised the importance of tissue-specific regulation of glucocorticoid
      availability by the 11 beta-hydroxysteroid dehydrogenase (11HSD) isozymes, which
      inter-convert active glucocorticoids and their inactive metabolites. The
      expression of both type 1 and type 2 11HSDs in the arterial wall suggests that
      prereceptor metabolism of glucocorticoids may have a direct impact on vascular
      physiology. Indeed there is evidence that 11HSDs influence glucocorticoid
      mediated changes in vascular contractility, vascular structure, the inflammatory
      response to injury and the growth of new blood vessels. Hence, inhibition of
      11HSD isozymes may provide a novel therapeutic target in vascular disease.

PMID- 16416028
TI  - Genetics of early mammalian folliculogenesis.
AB  - Early ovarian folliculogenesis begins with the breakdown of germ cell clusters
      and formation of primordial follicles. Primordial follicles are the smallest
      ovarian follicle units continuously recruited to grow into primary and more
      advanced ovarian follicles. Genes expressed in the germ cells such as Figla,
      Nobox, Kit and Ntrk2, as well as genes expressed in the surrounding somatic cells
      such as Foxl2, Kitl and Ngf, play critical functions during early
      folliculogenesis. Transgenic mice continue to provide important insights into the
      genetic pathways that regulate early mammalian folliculogenesis. Genes critical
      in early folliculogenesis are important determinants of reproductive life span
      and represent candidate genes for human ovarian failure.

PMID- 16416029
TI  - Antimicrobial skin peptides and proteins.
AB  - Human skin is permanently exposed to microorganisms, but rarely infected. One
      reason for this natural resistance might be the existence of a 'chemical barrier'
      consisting in constitutively and inducibly produced antimicrobial peptides and
      proteins (AMPs). Many of these AMPs can be induced in vitro by proinflammatory
      cytokines or bacteria. Apart from being expressed in vivo in inflammatory
      lesions, some AMPs are also focally expressed in skin in the absence of
      inflammation. This suggests that non-inflammatory stimuli of endogenous and/or
      exogenous origin can also stimulate AMP synthesis without inflammation. Such
      mediators might be ideal 'immune stimulants' to induce only the innate
      antimicrobial skin effector molecules without causing inflammation.

PMID- 16416030
TI  - Metastasis: cell-autonomous mechanisms versus contributions by the tumor
      microenvironment.
AB  - The fatality of cancer predominantly results from the dissemination of primary
      tumor cells to distant sites and the subsequent formation of metastases. During
      tumor progression, some of the primary tumor cells as well as the tumor
      microenvironment undergo characteristic molecular changes, which are essential
      for the metastatic dissemination of tumor cells. In this review, we will discuss
      recent insights into pro-metastatic events occurring in tumor cells themselves
      and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of
      cell polarity and alterations in cell-cell and cell-matrix adhesion as well as
      deregulated receptor kinase signaling, which together support detachment,
      migration and invasion of tumor cells. On the other hand, the tumor stroma,
      including endothelial cells, fibroblasts and cells of the immune system, is
      engaged in an active molecular crosstalk within the tumor microenvironment.
      Subsequent activation of blood vessel and lymph vessel angiogenesis together with
      inflammatory and immune-suppressive responses further promotes cancer cell
      migration and invasion, as well as initiation of the metastatic process.

PMID- 16416032
TI  - Peritoneal mesothelioma: an unusual cause of an acute phase response presenting
      to the rheumatologist.
AB  - The presence of an acute phase response may pre-date the eventual diagnosis of
      malignant disease by months or even years. We describe two patients referred to
      the rheumatology clinic, in which extensive investigation failed to identify an
      underlying cause to account for the presenting symptoms and an associated acute
      phase response. Several months later, repeated abdominal CT scans revealed an
      abnormality and subsequent laparoscopic biopsy confirmed a diagnosis of
      peritoneal mesothelioma.

PMID- 16416031
TI  - Texture analysis of X-ray radiographs of iliac bone is correlated with bone micro
      CT.
AB  - INTRODUCTION: Alteration of bone trabecular architecture is a predictor of
      fracture risk in osteoporosis. Until now, microarchitecture can only be measured
      on a bone biopsy, thus limiting microarchitecture analysis in routine clinical
      practice for osteoporosis. Texture analysis on X-ray images has been advocated to
      be a suitable means to assess two-dimensional (2-D) microarchitecture in the
      research field. But little is known about the relationships between three
      dimensional (3-D) architecture and texture analysis, particularly in clinical
      practice. The purposes of the study were: (1) to explore the relationship between
      3-D histomorphometric parameters and 2-D texture analysis, and (2) to see if
      cortical assessment may influence results. METHODS: In this study, the
      anterosuperior part of the iliac bone was removed from 24 cadavers. Large samples
      were prepared and comprised of the crest and a strip of bone approximately 3 cm
      wide and 5 cm long. These large specimens were used in order to preserve bone
      architecture; they also corresponded to the location used by histomorphometrists
      for the diagnosis of metabolic bone diseases on iliac crest biopsies. Bone
      samples were examined with a microcomputed tomograph for 3-D microarchitecture
      [BV/TV, C.BV/C.TV, Tb.P(f), structure model index (SMI), Tb.Th, Tb.N, Tb.Sp].
      Texture analysis was done by several methods (skeletonization, run lengths,
      fractal techniques) from X-ray projection images. No correlation was found
      between bone mass parameters (BV/TV and C.BV/C.TV, which take into account both
      cortical and trabecular bone) and texture parameters. RESULTS: However, when
      specific descriptors of trabecular bone microarchitecture were used, several
      relationships with texture parameters were found [(Tb.N)/BOUND, r=0.628;/VGLN,
      r=0.596;/Fractal D, r=0.569]. CONCLUSION: When multiple correlations were used,
      the correlation coefficients were markedly improved with trabecular
      characteristics. X-ray texture analysis seemed to be a suitable approach for 2-D
      bone microarchitecture assessment. Furthermore, there is a good correlation
      between texture analysis of X-ray radiographs and 3-D bone microarchitecture
      assessed by microcomputed tomography.

PMID- 16416033
TI  - Unusually diffuse idiopathic calcinosis cutis.
AB  - Calcifications in idiopathic calcinosis cutis are most commonly localized to one
      area. We herein report a 66-year-old woman with idiopathic calcinosis cutis who
      unusually exhibited widespread calcific deposits. In this report, we will also
      briefly discuss the pathogenesis, differential diagnosis, and current treatment
      of this disease.

PMID- 16416034
TI  - Treatment of intracranial aneurysms: techniques and specialisation and debate.

PMID- 16416035
TI  - The aneurysm "clip or coil" debate.

PMID- 16416036
TI  - Intracranial aneurysms: is there still a place for neurosurgery?

PMID- 16416037
TI  - Managed care, inter-agency linkages, and outpatient substance abuse treatment.
AB  - : Although treatment of co-occurring behavioral and physical health problems
      could be facilitated by the linkages between health care providers, it is
      uncertain how such inter-agency linkages are affected by managed care. We used a
      sample of 167 service linkages to examine the effects of managed care
      arrangements on inter-agency communication, coordination, and perceived
      effectiveness. These linkages were identified based on interviews with 62
      outpatient substance abuse treatment units in 2000. Results indicate that
      frequency of communication and inter-agency coordination are positively related
      to several managed care arrangements and may moderate the relationships between
      managed care arrangements and perceived effectiveness.

PMID- 16416038
TI  - Cardiovascular risk in Cushing's syndrome.
AB  - Chronic cortisol hypersecretion causes central obesity, hypertension, insulin
      resistance, dyslipidemia, protrombotic state, manifestations which form a
      metabolic syndrome in all patients with Cushing's syndrome. These associated
      abnormalities determine an increased cardiovascular risk not only during the
      active phase of the disease but also long after the "biomedical remission".
      Clinical management of these patients should be particularly careful in
      identifying global cardiovascular risk. Considering that remission from
      hypercortisolism is often difficult to achieve care and control of all
      cardiovascular risk factors should be one of the primary goals during the follow
      up of these patients. Extending the indications of the recent consensus on
      Cushing's syndrome, we suggest to carry out an OGTT to avoid underestimation of
      diabetes mellitus, an echocardiography and Doppler ultrasonography of the
      epiaortic vessels in all patients at diagnosis and during follow-up.

PMID- 16416040
TI  - Sarcomeric proteins in hypertrophied and failing myocardium: an overview.
AB  - This collection of papers covers developments in a rapidly growing area,
      sarcomeric proteins in hypertrophied and failing myocardium. Advances in our
      understanding of the biochemistry and biophysics of crossbridge cycling,
      contributions of thick versus thin filament and the emerging role of titin, the
      importance and mechanisms of mutations in causing disease, and an integrated
      understanding of the consequences of sarcomeric protein alterations at the organ
      level are discussed.

PMID- 16416039
TI  - PPAR-gamma in Cushing's disease.
AB  - The majority of pituitary tumors that cause Cushing's disease are small (<1 cm
      diameter), and most disease morbidity is due to the effects of elevated, non
      suppressible, ACTH levels that these tumors secrete. Tumor-derived ACTH leads to
      adrenal-derived steroid hypersecretion and results in many disabling and
      sometimes life-threatening symptoms including abnormal fat deposition, skin
      thinning, psychological disturbances, hypertension, diabetes, osteoporosis and
      muscle weakness. Cushing's disease is associated with high morbidity and
      ultimately mortality. In experienced specialized centers, 70% of corticotroph
      microadenomas can be successfully resected by transsphenoidal pituitary surgery.
      However, surgical "cure" rates for larger ACTH-secreting pituitary tumors are
      achieved in only 30% of cases, and recent reports highlight a significant
      recurrence rate after longer term follow-up even in smaller tumors. Post-surgical
      persistence of ACTH hypersecretion may require pituitary-directed radiation, but
      this treatment may take some time to be effective, and like extensive surgical
      pituitary tumor resection, ultimately leads to partial- or total hypopituitarism
      in approximately 80% of cases. Although hypercortisolism may be completely
      resolved by adrenalectomy, this procedure does not suppress, and may act as a
      stimulus to pituitary tumor growth, and is associated with other co-morbidity.
      Although some currently available drug-based treatments for Cushing's disease
      effectively control hypercortisolism, their drawback has been that they do not
      impact on pituitary tumor growth. Recent studies have identified the potential
      utility of peroxisome-proliferator activating receptor-gamma (PPAR-gamma) novel
      ligands in in vitro, and in vivo Cushing's disease models, and have paved the way
      for early clinical studies to develop novel therapeutic approaches in Cushing's
      disease.

PMID- 16416041
TI  - Kinetics and energetics of the crossbridge cycle.
AB  - Myosin heads interacting with actin filaments, a process fueled by MgATP and
      regulated by calcium, powers the pump-like action of the human heart. Hydrolysis
      of MgATP, the competition between MgATP, its products of hydrolysis, and actin
      for binding to myosin, and the sequence of shifting affinities in that
      competition, constitute the central mechanism of muscular contraction. The force,
      work, and power produced during the cardiac cycle stems from an isomerization of
      the myosin head that is closely associated with strong binding of myosin to actin
      and release of phosphate. While fluctuations of intracellular [Ca2+] bound to
      troponin and related shifts in tropomyosin on the thin filaments regulate the
      number of crossbridges on a beat-to-beat basis, the oscillatory work produced is
      augmented by a delayed force response to stretch that develops during diastole.
      This stretch-activated myogenic response is facilitated by specialized
      myofilament structures, including actin-binding portions of the myosin essential
      light chain and myosin binding protein C, which are thought to guide and orient
      the myosin head or enhance thin filament activation. Phosphorylation of the
      myosin regulatory light chain, myosin binding protein C, and troponin T also
      assist in this regard. Animal models show isoform shifts in myosin and other
      myofibrillar proteins have major effects on power output, but isoform shifts in
      human myocardium are modest at best and are therefore likely to play only a minor
      role in modulating crossbridge kinetics compared to disease-related post
      translational modifications of the contractile proteins and to changes in their
      chemical environment.

PMID- 16416042
TI  - Thick filament proteins and performance in human heart failure.
AB  - Modifications in thick filament protein content and performance are thought to
      underlie contraction-relaxation dysfunction in human heart failure. It has been
      found that myofibrillar Mg.ATPase is reduced in failing myocardium, which may be
      due in part to the reduction in alpha-myosin heavy chain (MHC) isoform content
      from approximately 5-10% in normal myocardium to <2% in failing myocardium. The
      physiological importance of this seemingly small amount of alpha-MHC appears
      substantiated by the development of cardiopathologies in humans with mutated
      alpha-MHC at normal abundance. Therefore, the replacement of alpha-MHC by beta
      MHC (possessing slower actomyosin enzymatic kinetics) may underlie to a
      significant degree the reduced myocardial shortening velocity and reduced
      relaxation function in human heart failure. The atrial isoform of myosin
      essential light chain (ELC) may replace up to 25% of the ventricular isoform in
      failing ventricles and in so doing promotes myocardial shortening velocity. An
      elevated accumulation of the higher performing atrial-ELC, unlike the reduced
      content of the higher performing alpha-MHC, is therefore considered a
      compensatory response in heart failure. Phosphorylation of the myofilament
      proteins myosin regulatory light chain and troponin-I are both reduced in heart
      failure and collectively result in an elevated myofilament sensitivity to calcium
      activation, which inhibits relaxation function. These and other modifications in
      thick filament proteins, as discussed in this review, directly affect mechanical
      power output and relaxation function of the myocardium and thereby may be
      considered to cause or in some cases to compensate for the otherwise ineffective
      myocardial performance in heart failure.

PMID- 16416043
TI  - Thin filament remodeling in failing myocardium.
AB  - While the remodeling process in myocardial failure involves changes in
      ventricular structure and performance, it is now appreciated that it is also
      associated with changes in thin filament composition and function. As is
      discussed, changes at the level thick filament may affect thin filament
      activation in heart failure. Alterations in actin, troponin and tropomyosin
      isoform composition do not appear to be significant factors in human heart
      failure. In contrast, proteolytic degradation of troponin subunits are likely to
      be playing a functional role in some forms of cardiomyopathy (e.g. ischemic).
      Finally, phosphorylation of troponin I and troponin T by kinases (most notably
      protein kinase C) substantially affect thin filament function in failing human
      myocardium. These findings indicate that functional deficits in thin filament
      function in failing myocardium are largely reversible and create the potential
      for future targeted therapies in the treatment of this deadly disease.

PMID- 16416044
TI  - Titin: physiological function and role in cardiomyopathy and failure.
AB  - Titin is a giant protein that constitutes the third myofilament of the sarcomere.
      Single titin molecules anchor in the Z-disk and extend all the way to the M-line
      region of the sarcomere. Successive titin molecules are arranged head-to-head and
      tail-to-tail, providing a continuous filament along the full length of the
      myofibril. The majority of titin's I-band region is extensible and functions as a
      molecular spring that when extended develops passive force. We will discuss
      mechanisms for adjusting titin-based force, including alternative splicing and
      posttranslational modifications. Multiple biological functions can be assigned to
      different regions of the titin molecule. In addition to titin's role in
      determining passive muscle stiffness, recent evidence suggests a role in protein
      metabolism, compartmentalization of metabolic enzymes, binding of chaperones, and
      positioning of the membrane systems of the T-tubules and sarcoplasmic reticulum.
      We will also discuss titin-based force adjustments that occur in various muscle
      diseases and several disease-causing titin mutations that have been discovered.
      We will focus on the role of titin in heart failure patients that was recently
      investigated in patients with end-stage heart failure due to non-ischemic dilated
      cardiomyopathy. In end-stage failing hearts, compliant titin isoforms comprise a
      greater percentage of titin and changes in titin isoform expression in heart
      failure patients with DCM significantly impact diastolic filling by lowering
      myocardial stiffness.

PMID- 16416045
TI  - Sarcomeric protein mutations in dilated cardiomyopathy.
AB  - This review aims to provide a concise summary of the DCM associated mutations
      identified in the proteins of the sarcomere and cytoskeleton, and discuss the
      reported effects of the mutations, as determined by functional studies, and in
      relation to the known structure of the protein affected. The mechanisms by which
      single missense mutations in the proteins of the sarcomere can lead to similar
      diseases as those caused by mutations in the proteins of the sarcolemma and
      cytoskeleton, are still unknown. However, a wide variety of mutations being
      associated with DCM suggests a complex mechanism shared by the proteins affected.
      The DCM mutations reviewed here are those of the beta-myosin heavy chain (beta
      MHC), myosin binding protein-C (MyBP-C), actin, alpha- tropomyosin (Tm), troponin
      T (TnT), troponin I (TnI), troponin C (TnC), of the sarcomere, and titin, T-cap,
      desmin, vinculin, and muscle LIM protein (MLP) of the cytoskeleton.

PMID- 16416046
TI  - Sarcomeric proteins and familial hypertrophic cardiomyopathy: linking mutations
      in structural proteins to complex cardiovascular phenotypes.
AB  - Hypertrophic Cardiomyopathy (HCM) is a relatively common primary cardiac disorder
      defined as the presence of a hypertrophied left ventricle in the absence of any
      other diagnosed etiology. HCM is the most common cause of sudden cardiac death in
      young people which often occurs without precedent symptoms. The overall clinical
      phenotype of patients with HCM is broad, ranging from a complete lack of
      cardiovascular symptoms to exertional dyspnea, chest pain, and sudden death,
      often due to arrhythmias. To date, 270 independent mutations in nine sarcomeric
      protein genes have been linked to Familial Hypertrophic Cardiomyopathy (FHC),
      thus the clinical variability is matched by significant genetic heterogeneity.
      While the final clinical phenotype in patients with FHC is a result of multiple
      factors including modifier genes, environmental influences and genotype, initial
      screening studies had suggested that individual gene mutations could be linked to
      specific prognoses. Given that the sarcomeric genes linked to FHC encode proteins
      with known functions, a vast array of biochemical, biophysical and physiologic
      experimental approaches have been applied to elucidate the molecular mechanisms
      that underlie the pathogenesis of this complex cardiovascular disorder. In this
      review, to illustrate the basic relationship between protein dysfunction and
      disease pathogenesis we focus on representative gene mutations from each of the
      major structural components of the cardiac sarcomere: the thick filament (beta
      MyHC), the thin filament (cTnT and Tm) and associated proteins (MyBP-C). The
      results of these studies will lead to a better understanding of FHC and
      eventually identify targets for therapeutic intervention.

PMID- 16416047
TI  - Functional consequences of sarcomeric protein abnormalities in failing
      myocardium.
AB  - Sarcomeric protein abnormalities have been recognized for many years in heart
      failure due to dilated cardiomyopathy (DCM). In contrast, virtually nothing is
      known about myofilament abnormalities in heart failure occurring in association
      with diastolic dysfunction. With the exception of sarcomeric protein mutations
      that cause DCM, the most important mechanism of myofilament dysfunction in DCM is
      probably altered post-translational modification, in particular the
      phosphorylation state of troponins I and T and possibly myosin light chain. Other
      modifications, including oxidation and glycation, may also play a role. Myosin
      heavy chain isoform switching occurs in human heart failure, but its functional
      significance is uncertain. Myofilament abnormalities contribute significantly to
      myocardial dysfunction in DCM, although their relative importance compared with
      abnormal calcium handling is debated. One consistent functional abnormality in
      DCM is increased myofilament calcium sensitivity of tension generation, which
      contributes to slowed or incomplete relaxation. More recently, decreases in the
      optimal frequency of myofilament work and power generation have been recognized.
      These changes may contribute to depression of the force-frequency relation in
      DCM. Altered mechanoenergetics constitute one of the most important
      manifestations of myofilament dysfunction in heart failure. DCM and hemodynamic
      overload are associated with more economical and efficient energy utilization by
      the contractile machinery, which may be protective of the myocardium. This change
      is strongly associated with depressed myofibrillar ATPase activity. We speculate
      that the effectiveness of mechanical therapies such as resynchronization may at
      least in part be related to improved mechanical function without loss of this
      mechanoenergetic advantage.

PMID- 16416048
TI  - The re-assimilation of ammonia produced by photorespiration and the nitrogen
      economy of C3 higher plants.
AB  - Photorespiration involves the conversion of glycine to serine with the release of
      ammonia and CO(2). In C(3) terrestrial higher plants the flux through glycine and
      serine is so large that it results in the production of ammonia at a rate far
      exceeding that from reduction of new nitrogen entering the plant. The
      photorespiratory nitrogen cycle re-assimilates this ammonia using the enzymes
      glutamine synthetase and glutamine:2-oxoglutarateaminotransferase.

PMID- 16416049
TI  - The influence of bridging ligand electronic structure on the photophysical
      properties of noble metal diimine and triimine light harvesting systems.
AB  - This manuscript discusses the photophysical behavior of transition metal
      complexes of Ru(II) and Os(II) employed in development of light harvesting arrays
      of chromophores. Particular emphasis is placed on the relationship between the
      photophysical behavior of complexes having metal-to-ligand charge transfer (MLCT)
      excited states and the electronic characteristics of bridging ligands used in
      preparing oligometallic complexes. Examples are presented that discuss
      intramolecular energy migration in complexes having two distinct MLCT
      chromophores with bridging ligands that only very weakly couple the two
      chromophores. In addition, systems having bridging ligands with localized triplet
      excited states lower in energy than the MLCT state of the metal center to which
      they are attached are discussed. These systems very often have excited states
      localized on the bridging ligand with excited state lifetimes on the order of
      tens of microseconds. Finally, systems having Fe(II) metal centers, with very low
      energy MLCT states, are discussed. In complexes also containing bridging ligands
      with low energy triplet states, energy partitioning between the Fe center MLCT
      state (or Fe localized ligand field states) and the ligand triplet state is
      observed; the two states relax to the ground state via parallel pathways, but the
      Fe(II) center does not serve as an absolute excitation energy sink.

PMID- 16416050
TI  - Mimicking the electron donor side of Photosystem II in artificial photosynthesis.
AB  - This review focuses on our recent efforts in synthetic ruthenium-tyrosine
      manganese chemistry mimicking the donor side reactions of Photosystem II.
      Tyrosine and tryptophan residues were linked to ruthenium photosensitizers, which
      resulted in model complexes for proton-coupled electron transfer from amino
      acids. A new mechanistic model was proposed and used to design complexes in which
      the mechanism could be switched between concerted and step-wise proton-coupled
      electron transfer. Moreover, a manganese dimer linked to a ruthenium complex
      could be oxidized in three successive steps, from Mn (2) (II,II) to Mn (2)
      (III,IV) by the photo-oxidized ruthenium sensitizer. This was possible thanks to
      a charge compensating ligand exchange in the manganese complex. Detailed studies
      of the ligand exchange suggested that at high water concentrations, each
      oxidation step is coupled to a proton-release of water-derived ligands, analogous
      to the oxidation steps of the manganese cluster of Photosystem II.

PMID- 16416051
TI  - Uphill energy transfer from long-wavelength absorbing chlorophylls to PS II in
      Ostreobium sp. is functional in carbon assimilation.
AB  - From the algal genus Ostrobium two species are known which express a chlorophyll
      antenna absorbing between 710 and 725 nm to a different extent. In a comparative
      study with these two species it is shown that quanta absorbed by this long
      wavelength antenna can be transferred to PS II leading to significant PS II
      related electron transfer. It is documented that under monochromatic far red
      light illumination growth continues with rather high efficiency. The data show
      that the uphill-energy transfer to PS II reduces the quantum yield under white
      light significantly. It is discussed that this strategy of energy conversion
      might play a role in special environments where far red light is the predominant
      energy source.

PMID- 16416052
TI  - Monte Moses and Adelaide Carpenter: Duke, 1974-1976.
AB  - This memoir recounts the scientific threads in Monte Moses's laboratory during
      1974-1976.

PMID- 16416054
TI  - [Family doctor-based health care].
AB  - The idea of family doctor-based health care corresponds to a social necessity for
      economical health care and a basic requirement for family doctors. However, this
      request is turned into the opposite by the legal description of a "particularly
      qualified family doctor". Economic interests dominate, dissect the family doctor
      level and influence long-standing family doctor-patient relationships and put the
      performance of social goals into question. Against that, the Family Doctor
      Association is setting the concept for family doctor-based integrated care, which
      also places quality demands, but does not exclude physicians basically or by
      selection of the compulsory health insurance fund.

PMID- 16416053
TI  - In vivo effects of antiviral acyclic nucleoside phosphonate 9-[2
      (phosphonomethoxy)ethyl]adenine (adefovir) on cytochrome P450 system of rat liver
      microsomes.
AB  - Interference of antiviral agent adefovir, i.e. 9-[2
      (phosphonomethoxy)ethyl]adenine (PMEA) with microsomal drug metabolizing system
      was investigated in rats. The content of total liver cytochrome P450 (CYP) was
      lowered while that of its denaturated form, P420, was elevated in animals
      intraperitoneally treated with PMEA (25 mg/kg). Similar effect was observed after
      treatment with a prodrug of adevofir, adefovir dipivoxil (bisPOM-PMEA). The
      CYP2E1-dependent formation of 4-nitrocatechol from p-nitrophenol was diminished,
      though the specific activity of p-nitrophenol hydroxylase remained unchanged.
      PMEA had no influence on expression of CYP2E1 protein and mRNA and mRNAs of other
      P450 isoenzymes (1A1, 1A2, 2C11, 3A1, 3A2, and 4A1). It may be concluded that
      repeated systemic administration of higher doses of PMEA results in a partial
      degradation of rat CYP protein to inactive P420.

PMID- 16416055
TI  - [Potentials and limitations of stem cell therapy in myocardial disease].
AB  - Acute myocardial infarction (MI) leads to myocardial necrosis and is, by nature,
      an irreversible injury. The major goal to reverse left ventricular remodeling
      would be the enhancement of regeneration of cardiac myocytes as well as the
      stimulation of neovascularization within the infarct area, by repopulation of the
      injured myocardium with healthy autologous cells. In March 2001, the first
      patient was treated with direct intracoronary administration of autologous
      mononuclear bone marrow cells after acute MI. As improvements in myocardial
      function and perfusion could be detected 3 months later without any complications
      - a study was initiated in Dusseldorf. Until now 40 patients have been
      investigated. After a three month follow-up period, significant improvements
      concerning myocardial function, perfusion and metabolism could be obtained. This
      therapeutical effect may be attributed to bone marrow cell-associated myocardial
      regeneration and neovascularization. These results demonstrate that functional
      and metabolic regeneration of infarcted myocardium can be safely realized in
      humans by bone marrow mononuclear cell transplantation.

PMID- 16416056
TI  - [Modern supplying concepts--what has been achieved with medical supplying
      centers].
AB  - In the first quarter of this year, the number of medical supplying centers rose
      from around 50 to 126, and in September 2005, 192 medical supplying centers
      existed in Germany. These medical supplying centers predominantly include working
      groups of physician communities. The number of medical supplying centers with
      working groups in hospitals will continue to increase. A medical establishment
      wave is however not expected. The investment and initial costs represent a high
      risk. Established physicians often feel a medical supplying center as
      competition. The hospital must consider the effects on the number of patients
      being referred as a carrier medical supplying center therefore compellingly. The
      medical supplying center extends the forms of the ambulatory care. They cannot
      guarantee complete covering supply. The establishment of medical supplying
      centers does not have recognizable effects on the problem of a lack of physicians
      in the new states of the Federal Republic.

PMID- 16416057
TI  - [18 months law for the modernisation of the SHI--review and prospects].
AB  - Balance of the law for the modernisation of the statutory health insurance (SHI)
      (GKV-Modernisierungsgesetz-GMG) is contradictory as measured by the original
      objectives. Although the legislators curtailed benefits and raised the co
      payments, those insured could not profit from lower contributions. The
      anticipated lowering of the ancillary wage costs was missing thereby. However,
      many SHI funds could settle debts, but the expenditures rose again in 2005. The
      financial situation of most SHI funds is still strained. The new federal
      government will have to tackle a further and sustainable reform of the statutory
      health insurance soon.

PMID- 16416058
TI  - [Risk adapted therapy in vascular diseases: antihypertensive treatment in
      peripheral arterial disease].
AB  - Arterial hypertension must also be consistently treated in patients with PAD.
      Current guidelines and recommendations have to be considered, although in some
      patients the walk performance may be affected temporary by blood pressure
      dropping. In PAD, ideal antihypertensives are ACE inhibitors, AT1 receptor
      antagonists, calcium channel blockers and also alpha receptor blockers in
      combination. Beta receptor blockers-indicated in coronary heart disease-do not
      influence pain-free walking distance (PFWD) in patients with PAD. Diuretics
      should only be given in low dosage and in combination with other antihypertensive
      drugs in order to avoid a decrease of blood flow ability with clinical events.

PMID- 16416059
TI  - [Risk adapted therapy of vascular diseases--basic therapy of dys- and
      hyperlipoproteinemia].
AB  - The target values in the treatment of patients with dys- and hyperlipoproteinemia
      are dependent on the underlying risk factors and the already existing vascular
      complications, respectively. The target value for patients with manifest vascular
      complications and for diabetics is <2.6 mmol/l (100 mg/dl) for LDL cholesterol.
      Results of recent studies show that in these high risk patients the target value
      for LDL Cholesterol should be </=1.8 mmol/l (70 mg/dl). Triglycerides should
      generally be lowered to <1.7 mmol/l (150 mg/dl) and HDL cholesterol should be
      >1.0 mmol/l (40 mg/dl). In high risk patients even higher HDL levels should be
      reached (men: >1,2 mmol/l (45 mg/dl), women: >1,4 mmol/l (55 mg/dl)). Basic
      therapy measurements of hyperlipoproteinemia are changes in diet, reduction of
      body weight and physical training after exclusion of contraindications. If the
      goals of therapy cannot be reached with these measures, drug therapy is
      indicated. In hypercholesterolemia the first choice are statins, which show the
      best data concerning endpoint studies. Other therapeutic options are ezetimibe,
      nicotinic acid derivates with retarded release marketed in Germany as Niaspan,
      fibrates and in single cases anion exchanger. In patients with
      hypertriglyceridemia fibrates are effective, but there exist very few endpoint
      studies for this substance group. Fish oils can also be used in this case. Mixed
      forms of hyperlipoproteinemia are the most difficult disorders to treat, in these
      cases the therapeutic decision should depend on whether the hypercholesterolemia
      or the hypertriglyceridemia is dominating.

PMID- 16416060
TI  - [Management of diabetes mellitus in patients with angiopathies].
AB  - Nowadays, about 6-8% of the German population suffers from diabetes mellitus
      mostly type 2 but in patients with angiopathies about 30% have known diabetes and
      a further 30% have newly diagnosed diabetes or impaired glucose tolerance.
      Therefore diagnosis and therapy of glucose impairment play a central role for
      management of these patients. The antidiabetic therapy for secondary prevention
      of cardiovascular disease has to be embedded in a multifactorial concept with
      management of hypertension, hyperlipidemia and hypercoagulability. The management
      of diabetes following guidelines is a stepwise therapy with lifestyle
      interventions (diet, exercise) and oral drugs or insulin. Metformin has shown
      favorable outcome in overweight patients if aware of side effects; insulin is a
      safe drug in multimorbid patients and with planned interventions or operations.
      We are awaiting the results of multiple endpoint studies with newer antidiabetic
      drugs which may change our current concept of management of diabetes mellitus in
      these patients in the near future.

PMID- 16416061
TI  - [Improved analysis of left ventricular function using three-dimensional
      echocardiography].
AB  - Left ventricular geometry and function are important pathophysiologic and
      prognostic parameters. However, especially in patients with cardiac pathologies
      left ventricular geometry can be complex. Quantification of left ventricular
      volumes using conventional two-dimensional echocardiography is only possible when
      simplifying assumptions of left ventricular geometry are made. In contrast three
      dimensional echocardiography allows direct quantification of left ventricular
      volumes even in complex distortions of left ventricular shape. The availability
      of real-time three-dimensional echocardiography has brought this technique into
      clinical practice. Three-dimensional echocardiography is a technique that may be
      used as a routine echocardiographic method in the near future.

PMID- 16416062
TI  - [Tissue doppler for the assessment of LV function--what makes sense?].
AB  - Tissue Doppler based velocity and deformation measurements allow the quantitative
      and thus objective assessment of myocardial function. So far, many techniques and
      parameters have been developed, most of which require an explanation for the
      clinical user. This article reviews relevant tissue Doppler parameters and gives
      examples of the current clinical usage of this technique.

PMID- 16416063
TI  - [Implementing integrated health care--current state and progress].
AB  - The legal framework for Integrated Health Care since 2004 offers many
      opportunities for health professionals and insurers in the competition for "high
      quality care". Germany's largest statutory health insurance fund, BARMER, has
      already developed around 100 Integrated Health Care Projects for a wide range of
      conditions. One important issue is the relationship to disease management
      programs. Our program "integrated cardiological care" combines both DMP and
      integrated health care and thus already shows good results with respect to
      patient acceptance as well as savings trough the changing patterns in
      interventional cardiology.

PMID- 16416064
TI  - [Quantification of valvular lesions in patients with left ventricular
      dysfunction].
AB  - Echocardiography is the preferred method for assessment of aortic and mitral
      valvular lesions. The pressure gradient in aortic stenosis may be misleading in
      patients with poor left ventricular function. Aortic valve area planimetry by
      transesophageal echocardiography results in a flow independent anatomic
      measurement. Low-dose dobutamine stress echocardiography provides important
      prognostic information. Quantitative Doppler echocardiography allows accurate
      assessment of mitral regurgitation severity. However, the definition of what is
      severe mitral regurgitation is different in patients with left ventricular
      dysfunction.

PMID- 16416065
TI  - [Atrial fibrillation: rate or rhythm control--individual patient management].
AB  - The treatment of atrial fibrillation still remains challenging in everyday
      practice. Even after the introduction of catheter ablation, the decision-making
      process about the type of therapy became more complex. The recently published
      guidelines of the American Heart Association, the American College of Cardiology,
      and the European Society of Cardiology clearly show therapeutic approaches for
      different types of atrial fibrillation. The fear of thromboembolism still forces
      the physician to restore sinus rhythm and achieve optimized anticoagulation.
      Based on large studies, we are able to decide for each patient individually
      whether oral anticoagulation or ASA is required. Future studies in a large cohort
      of patients are still necessary to clarify the value of interventional therapy in
      conjunction with antiarrhythmic drug therapy. These will provide patients with
      safe therapy and high quality of life despite presenting paroxysmal or persistent
      atrial fibrillation.

PMID- 16416066
TI  - [The role of cardiac pacing in atrial arrhythmia prevention].
AB  - Pathophysiological considerations, animal data and acute clinical tests suggest
      some benefit of cardiac pacing in the prevention of paroxysmal atrial
      tachyarrhythmia. While early clinical studies confirm this notion, data of
      randomized prospective trials at least are mixed. The equivocal effects of using
      alternative atrial pacing sites and/or dedicated preventive pacing algorithms
      leaves the question of how to predict the beneficial effect of antitachycardia
      pacing strategies in the individual patient. Since the answer is lacking, the
      mere intention to prevent atrial arrhythmias is not a valid pacing indication.
      Pacing for the bradycardia tachycardia syndrome, however, may benefit from
      preventive techniques in individual cases.

PMID- 16416067
TI  - [Cardiac resynchronization therapy: who is suitable? Who requires an additional
      ICD as a backup?].
AB  - Cardiac resynchronization therapy (CRT) has significant positive effects on the
      quality of life, enables patients to cope more efficiently with cardiopulmonary
      stress and leads to a reduction of total mortality in patients suffering from
      congestive heart failure NYHA classes III and IV, reduced ventricular function
      and left bundle branch block with a QRS complex wider than 150 ms. In a large
      number of patients suited for CRT, an additional defibrillator function seems to
      work out well concerning an additional prognostic improvement by means of
      reducing sudden cardiac death. Due to partially contradictory study outcomes, it
      still remains to be discussed whether all patients suited for CRT really need an
      ICD.

PMID- 16416068
TI  - [Use of risk factors in determining individual coronary risk].
AB  - The "Deutschland SCORE" has low predictive power and greatly overestimates the
      true risk of coronary heart disease in Germany. Widespread use of this score
      would lead to massive over-treatment. For this reason, we cannot recommend this
      score for general use.

PMID- 16416069
TI  - [Modern concepts of medical care--what has been achieved by the implementation of
      disease management programs?].
AB  - Since 2003, structured treatment programs for chronically ill patients (disease
      management programs; DMPs) have been under development in Germany. Virtually
      nationwide, programs in which physicians and patients can register are being
      offered for diabetes mellitus types 1 and 2, breast cancer, coronary heart
      disease and asthma/COPD. The medical content of the programs is determined on the
      basis of evidence-based medicine. Even though the effectiveness of structured
      treatment programs is documented for diabetes, adequate studies confirming the
      overall transferability of results to the German health care system are as yet
      lacking. Physicians above all strongly criticise the coupling of DMPs with the
      risk adjustment scheme of the statutory health insurance funds, as well as the
      large amount of paperwork involved.

PMID- 16416071
TI  - [Value of gated SPECT myocardial perfusion imaging for individual cardiac risk
      assessment].
AB  - Myocardial perfusion imaging enables not only accurate diagnosis of disease but
      also entails prognostic value. Myocardial perfusion SPECT contributes to
      assessment of future cardiac events independently of other clinical parameters. A
      normal stress myocardial perfusion scan is associated with a favorable prognosis
      independent of history, symptoms, and exercise electrocardiography test
      variables. Cardiac risk and benefit from invasive therapeutic strategies increase
      in relation to the severity of the abnormality of perfusion and function assessed
      by gated myocardial perfusion SPECT. Thus, stress myocardial perfusion imaging
      may serve as a gatekeeper for referral to coronary angiography enabling effective
      risk stratification in patients with suspected or documented coronary artery
      disease.

PMID- 16416070
TI  - [Impact of both cardiac-CT and cardiac-MR on the assessment of coronary risk].
AB  - Today's definition of coronary artery disease (CAD) comprises two forms:
      obstructive and non-obstructive CAD. The 31-72% chance of a life-threatening
      event-like a myocardial infarction-with non-obstructive CAD is well documented in
      numerous studies. The objective in modern strategies of diagnosis and therapy
      should therefore be expedient identification of patients at high risk for
      coronary events, who will benefit from a customized therapy. Before initiating
      diagnostic procedures of CAD, a well defined strategy should be pursued. There
      are two possible primary objectives: ASSESSMENT OF THE INDIVIDUAL RISK FOR A
      CORONARY EVENT: Assessment of the individual "absolute" risk for a coronary event
      is not possible using single traditional risk factors. The individual risk can be
      estimated by integrating several of the traditional risk factors into a scoring
      system. These so-called risk scores (e.g. Framingham score and Procam score),
      however, have been associated with shortcomings: insufficient discrimination of
      high-risk from low-risk individuals. The calcium score has therefore become
      increasingly established; this Agatston score is independent of the traditional
      risk factors, so there is no correlation between Agatston and Procam scores.
      Today, the calcium score is considered the superior test for identifying
      individuals at high risk for a coronary event and its use is recommended by the
      European Society of Cardiology (ESC) guidelines for prevention of cardiovascular
      diseases. PROOF OR EXCLUSION OF A HEMODYNAMICALLY SIGNIFICANT CORONARY STENOSIS:
      Another concept is the definitive proof or exclusion of a hemodynamically
      "significant" coronary narrowing. The probability of an obstructive CAD is
      traditionally assessed by the type of chest pain, age, gender and stress-ECG. In
      patients with a low probability of an obstructive CAD, cardiac catheterization is
      not indicated, whereas in patients with a high probability of a hemodynamically
      significant coronary stenosis, an invasive strategy should be performed. Since
      non-invasive coronary angiography (CTA) with cardiac-CT has been shown to provide
      a high negative predictive value, CTA (with good imaging quality) is suitable for
      ruling out a significant obstructive CAD in the group at intermediate risk for an
      obstructive CAD. Another approach could be a functional test to initially prove a
      relevant, inducible myocardial ischemia: In a large cohort it was shown that
      patients will only prognostically benefit from revascularization procedures if
      the ischemic myocardial area is greater than 10%. Therefore, the assessment of
      the extent of myocardial ischemia is the domain of modern stress imaging tests.
      Stress-echocardiography and myocardial scintigraphy have almost the same
      sensitivity (74-80%, 84-90%, respectively) and specificity (84-89%, 77-86%,
      respectively), which are considerably higher than for stress-ECG. Cardiac MR is
      most suitable for the assessment of myocardial perfusion, because it traces the
      first pass dynamics of gadolinium at rest and during stress in reproducible
      slices at an acceptable spatial and a high temporal resolution without ionizing
      radiation. Whether the non-invasive coronary angiography with cardiac-CT and the
      Adenosin-perfusion imaging with cardiac-MR will completely replace diagnostic
      cardiac catheterization and stress-echocardiography as well as myocardial
      scintigraphy remains to be evaluated in further studies.

PMID- 16416073
TI  - ["Integrated care"--the Essen concept: organizational strategies in the treatment
      of acute myocardial infarction].
AB  - The German "GKV-Modernisierungsgesetz" offers new opportunities for patient care.
      The concept of "integrated care" provides organizational structures for an
      standardized treatment of myocardial infarction by bridging the different sectors
      of the German health care system. Apart from guideline-based therapy, innovative
      diagnostic (cardiac MRI) and therapeutic (drug-eluting stents) techniques are
      implemented in the "integrated care" model as well. The "Herzinfarktverbund
      Essen" is the first national real world experience of the integrated care concept
      in the treatment of myocardial infarction.

PMID- 16416072
TI  - [Interventional therapy of acute ST-elevation myocardial infarction in a regional
      network].
AB  - BACKGROUND AND OBJECTIVES: Management of acute ST-elevation myocardial infarction
      (STEMI) demands rapid and complete reflow to the infarct related artery (IRA).
      Primary PCI (percutaneous coronary intervention) performed by experienced
      operators is superior to thrombolytic thrombolytic therapy and reduces mortality,
      occurrence of non-fatal reinfarction and stroke, but is not available in rural
      Germany. We established a regional infarction-network using established
      therapeutic guidelines comprising of 1 interventional center and 7 referring
      community hospitals without PCI facilities. PATIENTS AND METHODS: We analyzed 322
      patients with STEMI treated by PCI within the network; 160 patients were
      transferred from a community hospital without PCI facilities (transfer group
      (TG): 63.4 yrs., 71.8% men) and 162 patients were admitted directly to the
      interventional center (center group (CG): 61.7 yrs., 73.8% men). The interval
      from onset of symptoms to first medical contact was 205 minutes in TG, and 195
      minutes in CG (n.s.); 7.8% of the CG and 7.2% of the TG patients were in
      cardiogenic shock; 95% of patients completed 12- months of follow-up. RESULTS: In
      the TG, median transportation time to PCI was 54 minutes. PCI of the infarct
      related artery (IRA) was performed in 95.1% of TG patients and in 94.1% of CG
      patients. In addition, 96% of all patients received a GP IIb/IIIa receptor
      inhibitor. In case of pre-interventional application of GP IIb/IIIa receptor
      inhibitor 22.3% of patients revealed TIMI-3 flow of the IRA before PCI. After
      PCI, normalized flow to the IRAwas documented in 87.5% of CG versus 86.3% of TG.
      There were no differences between groups with respect to infarct size (TG vs. CG:
      CK 2482 vs. 2481 U/I; CKMB 302 vs. 264 U/I), mortality (30 days: 5.3 vs. 5.2%, 6
      months: 7.3 vs. 7.1%, 12 months: 7.9 vs. 7.8%); NYHA (1.41 vs. 1.43) and left
      ventricular ejection fraction (0.41 vs. 0.43). CONCLUSIONS: The organization of a
      regional STEMI-network with logistic alliance of community hospitals and one
      experienced interventional center ensures timely PCI treatment of patients with
      STEMI according to present guidelines even in rural areas, and relegates
      thrombolytic treatment to bail-out scenarios only.

PMID- 16416074
TI  - [MRI in chronic myocarditis].
AB  - In most cases inflammatory changes of the myocardium are asymptomatic. If
      inflammatory changes of the myocardium manifest with clinical symptoms, the
      condition is termed myocarditis. Myocarditis is regarded as a major cause for
      sudden death of young adults and accounts for up to 20% of the cases. In Europe
      viral infections represent the most important cause of myocarditis. In chronic
      myocarditis, viremia is often absent and myocardial fibrosis and dilated
      cardiomyopathy (DCM) resulting in heart failure can occur. The role of cardiac
      MRI in chronic myocarditis is not yet well understood. MRI is a sensitive tool
      detecting myocardial fibrosis on late images after application of paramagnetic
      contrast agents. The region of contrast accumulation is defined as "late
      enhancement" (LE). Data are available now suggesting that differentiating
      fibrosis due to myocardial infarction from inflammatory causes is facilitated
      using MRI late images. Fibrosis after ischemic infarction includes the
      subendocardial layer of the myocardium. If the subendocardial layer of the
      myocardium is not involved in the fibrosis, infarction is unlikely and can be
      reliably excluded as an important differential diagnosis in the vast majority of
      affected patients.

PMID- 16416075
TI  - [Surgical therapy of infective endocarditis].
AB  - Therapy of infective endocarditis (IE) remains a particular challenge due to a
      relative high morbidity and mortality. Cardiac surgery is established as a
      cornerstone in therapy for native valve endocarditis (NVE) as well as for
      prosthetic valve endocarditis (PVE) and is required in 30% of patients with
      active IE. The basic aim of surgery in IE is the radical debridement of infected
      tissue and reconstruction of valve function either by reconstructive valve
      surgery or valve replacement. Indication for surgery depends on several clinical
      variables, the main indication remains heart failure due to severe heart valve
      defects or prosthetic valve dysfunction. Surgical therapy of NVE can be performed
      with good clinical results in the early and late follow-up. Surgical therapy of
      PVE is still associated with quite high mortality up to 80% in some risk groups.
      This indicates the particular importance of focus evaluation and antibiotic
      prophylaxis after primary surgery for infective endocarditis.

PMID- 16416079
TI  - Formalin application in the treatment of chronic radiation-induced hemorrhagic
      proctitis induces acute deterioration of mucosal blood flow.

PMID- 16416080
TI  - Palliative laparoscopic resections for Stage IV colorectal cancer.
AB  - PURPOSE: Issues surrounding the safety and efficacy of palliative laparoscopic
      resections for patients with Stage IV colorectal cancer have not been explicitly
      examined in the literature. This article describes our experience with
      laparoscopic procedures for patients with Stage IV colorectal cancer and compares
      their perioperative outcomes to a contemporaneous group of patients with
      clinically curable (Stages I-III) disease. METHODS: A prospective database of
      laparoscopic resections for colorectal cancer performed between 1991 and 2002 was
      reviewed. Data regarding patient demographics, perioperative morbidity and
      mortality, operative times, conversion rates, and length of stay were extracted.
      Statistical analysis included chi-squared and Student's t-tests as required and
      P<or=0.05 was considered significant. RESULTS: A total of 375 cases were
      identified, of these 49 (13 percent) underwent laparoscopic palliative resections
      while 326 (87 percent) patients had resections for cure. When comparing
      palliative to curative procedures, there were no differences in intraoperative (4
      percent vs. 9 percent) or postoperative complications (14 percent vs. 12
      percent), perioperative mortality (8 percent vs. 4 percent), or length of
      hospital stay. Patients with Stage IV disease had larger tumors (5.4+/-2.3 cm vs.
      4.6+/-2.6 cm, P=0.04) which contributed to an increased rate of conversion (22
      percent vs. 11 percent, P=0.05) with most conversions secondary to tumor fixation
      or bulk (64 percent) preventing determination of resectability. CONCLUSIONS: A
      palliative laparoscopic resection is a safe and feasible option and presents
      acceptable morbidity and mortality in patients with Stage IV colorectal cancer.
      Importantly, in this difficult group of patients, our results compare favorably
      with those from previously published series of open procedures.

PMID- 16416081
TI  - Twelve years of endoscopic surveillance in a family carrying biallelic Y165C MYH
      defect: report of a case.
AB  - PURPOSE: We report the case of two siblings, clinically andendoscopically
      followed for 12 years, who displayed anattenuated adenomatous polyposis coli
      phenotype. METHODS: On workup for rectal bleeding with colonoscopy, we found
      multiple adenomas mainly right-sided in a 21-year-old female and the same colonic
      phenotype was observed in her 27-year-old brother. We made a clinical diagnosis
      of attenuated adenomatous polyposis coli and performed APC gene testing. Because
      they had refused the proposed ileorectal anastomosis surgical option, we planned
      a periodic, endoscopic follow-up. RESULTS: Gene testing did not confirm the
      clinical suspicion of attenuated adenomatous polyposis coli. Actually, we did not
      find anypathogenic mutation in APC gene and we recently identified a biallelic
      Y125C MYH defect. During the endoscopic follow-up, a progressive reduction of
      adenomas was seen. CONCLUSIONS: New insight colorectal cancer genetics have
      allowed definition of a new class of polyposis that applies to some patients with
      attenuated adenomatous polyposis coli phenotype as in the siblings we have
      described. To prevent colorectal cancer without recurring to surgery,
      colonoscopic polypectomy may be a suitable tool in controlling MYH polyposis.

PMID- 16416085
TI  - Meeting report for the 4th annual Complex Trait Consortium meeting: from QTLs to
      systems genetics.
AB  - The fourth annual meeting of the Complex Trait Consortium (CTC) was held in
      Groningen, the Netherlands on June 26-29, 2005. This meeting, which set a new
      attendance record, followed three previous and highly successful meetings. The
      focus at this meeting was on continued resource development and the exiting new
      field of systems genetics, the integration and anchoring of multi-dimensional
      data-types to underlying genetic variation. A new aspect at the meeting was the
      three-minute, 'come see my poster' presentations that generated significant
      interaction at the poster sessions. If the 2005 meeting is an indicator of things
      to come, future meetings promise to offer even more exciting research efforts to
      integrate high-throughput biological measurements with genetic variation to
      unravel the mechanisms responsible for inter-individual variation.

PMID- 16416086
TI  - Expression of a modified H19 RNA does not cause embryonic lethality in mice.
AB  - The imprinted H19 gene produces a noncoding RNA of unknown function. Targeted and
      transgenic mouse mutations have shown that this RNA can be deleted and
      overexpressed without adverse effect. Yet one mutation of the H19 gene displayed
      an embryonic lethal phenotype in the mouse--the expression of an RNA modified by
      a short insertion near the 5' end of the transcript (H19(Xba) allele). Expression
      of this RNA in transgenic mice conferred lethality at day 14 of development. The
      potential for this mutant to elucidate the function of the H19 RNA supported
      further investigation of the H19(Xba) phenotype. Since all H19(Xba) transgenic
      founders died as embryos, an experiment was designed to generate H19(Xba)
      expressing mice that could be maintained as an established line. This strategy
      took advantage of the maternal-specific expression of H19, passing an H19(Xba)
      knockin allele silently through males and transferring it to females only to
      generate animals for study. Surprisingly, H19(Xba) knockin mice are fully viable,
      whether the H19(Xba) allele is inherited paternally or maternally. Experiments to
      reproduce the original transgene-based lethality were also performed and yielded
      live-born transgene-expressing animals. These data demonstrate that, contrary to
      published reports, expression of the H19(Xba) RNA does not cause embryonic
      lethality in mice.

PMID- 16416087
TI  - Inefficient purifying selection: the mammalian Y chromosome in the rodent genus
      Mus.
AB  - Two related genes with potentially similar functions, one on the Y chromosome and
      one on the X chromosome, were examined to determine if they evolved differently
      because of their chromosomal positions. Six hundred fifty-seven base pairs of
      coding sequence of Jarid1d (Smcy) on the Y chromosome and Jarid1c (Smcx) on the X
      chromosome were sequenced in 13 rodent taxa. An analysis of replacement and
      silent substitutions, using a counting method designed for samples with small
      evolutionary distances, showed a significant difference between the two genes.
      The different patterns of replacement and silent substitutions within Jarid1d and
      Jarid1c may be a result of evolutionary mechanisms that are particularly strong
      on the Y chromosome because of its unique properties. These findings are similar
      to results of previous studies of Y chromosomal genes in these and other
      mammalian taxa, suggesting that genes on the mammalian Y evolve in a chromosome
      specific manner.

PMID- 16416088
TI  - Quantitative trait locus analysis for obesity reveals multiple networks of
      interacting loci.
AB  - Obesity is a highly heritable and genetically complex trait with hundreds of
      potential loci identified. An intercross of 513 F2 progeny between the SM/J x
      NZB/BINJ inbred mouse strains was generated to identify quantitative trait loci
      (QTL) that are involved in the weight of four fat pads: mesenteric, inguinal,
      gonadal, and retroperitoneal. Sex and lean body weight were treated as covariates
      in the analysis of these fat pads. This analysis uncoupled genetic effects
      related to overall body size from those influencing the adiposity of a mouse. We
      identified multiple significant QTL. QTL alleles associated with increased lean
      body weight and individual fat pad weights are contributed by the NZB background.
      Adiposity loci are distinct from these body size QTLs and high-adiposity alleles
      are contributed by the SM background. An extended network of epistatic QTL is
      also observed. A QTL on Chr 19 is the center of a network of eight interacting
      QTL, Chr 4 is the center of six, and Chr 17 the center of four interacting QTL.
      We conclude that interacting networks of multiple genes characterize the
      regulation of fat pad depots and body weight. Haplotype patterns and a literature
      driven approach were used to generate hypotheses regarding the identity of the
      genes and pathways underlying the QTL.

PMID- 16416089
TI  - Development of a deer mouse whole-genome radiation hybrid panel and comparative
      mapping of Mus chromosome 11 loci.
AB  - A 5000-rad whole-genome radiation hybrid cell panel (BW5000) was developed for
      mapping the deer mouse (Peromyscus maniculatus bairdii) genome. The panel
      consists of 103 cell lines and has an estimated marker retention frequency of
      63.9% (range, 28%-88%) based on PCR typing of 30 Type I (coding gene) and 25 Type
      II (microsatellite) markers. Using the composite Mus map, Type I markers were
      selected from six Mus chromosomes, 22 of which are on Mus Chr 11. Fifteen of the
      Mus Chr 11 markers were simultaneously mapped on an interspecific (P. maniculatus
      x P. polionotus) backcross panel to test the utility of the radiation hybrid
      panel, create a framework map, and help establish gene order. The radiation
      hybrids have effectively detected linkage in the deer mouse genome between
      markers as far apart as 6.7 cM and resolved markers that are, in the Mus genome,
      as close as 0.2 Mb. Combined results from both panels have indicated a high
      degree of gene order conservation of the telomeric 64 cM of Mus Chr 11 in the
      deer mouse genome. The remaining centromeric portion also shows gene order
      conservation with the deer mouse but as a separate linkage group. This indicates
      a translocation of that portion of Mus Chr 11 in P. maniculatus and is consistent
      with rearrangement breakpoints observed between Mus and other mammalian genomes,
      including rat and human. Furthermore, this separate linkage group is likely to
      reside in a chromosomal region of inversion polymorphism between P. maniculatus
      and P. polionotus.

PMID- 16416090
TI  - Angiogenesis and capillary maturation phenotypes associated with the Edpm3 locus
      on rat chromosome 3.
AB  - The quantitative trait locus (QTL) Edpm3 is one of a group of additively acting
      QTL ?responsible for the difference in estrogen-induced pituitary tumor growth
      between the tumor-susceptible F344 and tumor-resistant BN rat strains. The
      F344.BN-Edpm3(BN) rat strain was produced by moving the segment of rat Chr 3
      between D3Mgh7 and D3Mgh13, which contains the Edpm3 QTL, from the BN strain into
      the F344 genetic background. In a previous study, we used this congenic line to
      find that the BN allele of the Edpm3 QTL reduces tissue mass and S-phase fraction
      in the estrogen-induced rat pituitary tumor. We now report on the use of this
      congenic line to investigate the linkage of Edpm3 to tumor angiogenesis. Contrary
      to expectation, the F344.BN-Edpm3(BN) strain has significantly greater angiogenic
      activity than does F344 in both treated and untreated rats. Microvessel count
      (MVC), perivascular space, and number of nonattached pericytes/pericapillary
      fibroblasts are all elevated in the pituitary by chronic estrogen treatment and
      their values are significantly greater in F344.BN-Edpm3(BN) than F344. Thus,
      although there is greater angiogenic activity in the pituitary of estrogen
      treated F344.BN-Edpm3(BN) rats, there is a deficiency in capillary maturation
      compared with F344.

PMID- 16416091
TI  - The mutation causing the black-and-tan pigmentation phenotype of Mangalitza pigs
      maps to the porcine ASIP locus but does not affect its coding sequence.
AB  - The gene for agouti signaling protein (ASIP) is centrally involved in the
      expression of coat color traits in animals. The Mangalitza pig breed is
      characterized by a black-and-tan phenotype with black dorsal pigmentation and
      yellow or white ventral pigmentation. We investigated a Mangalitza x Pietrain
      cross and observed a coat color segregation pattern in the F2 generation that can
      be explained by virtue of two alleles at the MC1R locus and two alleles at the
      ASIP locus. Complete linkage of the black-and-tan phenotype to microsatellite
      alleles at the ASIP locus on SSC 17q21 was observed. Corroborated by the
      knowledge of similar mouse coat color mutants, it seems therefore conceivable
      that the black-and-tan pigmentation of Mangalitza pigs is caused by an ASIP
      allele a(t), which is recessive to the wild-type allele A. Toward positional
      cloning of the a(t) mutation, a 200-kb genomic BAC/PAC contig of this chromosomal
      region has been constructed and subsequently sequenced. Full-length ASIP cDNAs
      obtained by RACE differed in their 5' untranslated regions, whereas they shared a
      common open reading frame. Comparative sequencing of all ASIP exons and ASIP
      cDNAs between Mangalitza and Pietrain pigs did not reveal any differences
      associated with the coat color phenotype. Relative qRT-PCR analyses showed
      different dorsoventral skin expression intensities of the five ASIP transcripts
      in black-and-tan Mangalitza. The a(t) mutation is therefore probably a regulatory
      ASIP mutation that alters its dorsoventral expression pattern.

PMID- 16416092
TI  - Fine-mapping and candidate gene analysis of bovine spinal muscular atrophy.
AB  - Bovine spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative
      disease, has been mapped at moderate resolution to the distal part of Chromosome
      24. In this article we confirm this location and fine-map the SMA locus to an
      interval of approximately 0.8 cM at the very distal end of BTA24. Despite
      remarkable similarity to human SMA, the causative gene SMN can be excluded in
      bovine SMA. However, the interval where the disease now has been mapped contains
      BCL2, like SMN an antiapoptotic factor, and shown to bind to SMN. Moreover,
      knockout mice lacking the BCL2 gene show rapid motor neuron degeneration with
      early postnatal onset, as observed in bovine SMA. A comparative cattle/human map
      of the distal end of BTA24, based on the emerging bovine genome sequencing data,
      shows conserved synteny to HSA18 with hints of a segmental duplication and
      pericentric inversion just after the last available bovine marker DIK4971. This
      synteny lets us conclude that SMA is in immediate vicinity of the telomere.
      Candidate gene analysis of BCL2, however, excludes most of this gene, except its
      promoter region, and draws attention to the neighboring gene VPS4B, part of the
      endosomal protein-sorting machinery ESCRT-III which is involved in several
      neurodegenerative diseases.

PMID- 16416093
TI  - Mutation in the Sp1 motif of the bovine leptin gene affects its expression.
AB  - Leptin is expressed mainly by adipocytes and plays a crucial role in the
      regulation of energy expenditure, food intake, and adiposity. Using PCR
      heteroduplex analysis and sequencing, we investigated a C/G substitution in the
      promoter region of the bovine leptin gene. Application of the electrophoretic
      mobility shift assay showed that the C-->G transversion decreased the leptin gene
      promoter binding capacity for nuclear proteins. With real-time PCR and Western
      blotting, we showed that the leptin expression level was higher in cattle with
      the CC than with the GG genotype.

PMID- 16416094
TI  - Characterization of the bovine PRKAG3 gene: structure, polymorphism, and
      alternative transcripts.
AB  - The bovine PRKAG3 gene encodes the AMPK gamma3 subunit, one isoform of the
      regulatory gamma subunit of the AMP-activated protein kinase (AMPK). The AMPK
      plays a major role in the regulation of energy metabolism and mutations affecting
      the genes encoding the gamma subunits have been shown to influence AMPK activity.
      The gamma3 subunit is involved in the regulation of AMPK activity in skeletal
      muscle and strongly influences glycogen metabolism. Glycogen content in muscle is
      correlated to meat quality in livestock because it influences postmortem
      maturation process and ultimate pH. Naturally occurring mutations in the porcine
      PRKAG3 gene highly affect meat quality by influencing glycogen content before
      slaughter. We present the characterization of the bovine PRKAG3 gene and a
      polymorphism analysis in three cattle breeds. Thirty-two SNPs were identified
      among which 13 are in the coding region, one is in the 3' UTR, and 18 are in the
      introns. Five of them change an amino acid in the PRKAG3 protein sequence.
      Allelic frequencies were determined in the three breeds considered, and mutant
      alleles affecting the coding sequence are found at a very low frequency.
      Alternative splicing sites were identified at two positions of the gene,
      introducing heterogeneity in the population of proteins translated from the gene.

PMID- 16416095
TI  - Determination of resorcylic acid lactones in biological samples by GC-MS.
      Discrimination between illegal use and contamination with fusarium toxins.
AB  - An EU project, FAIR5-CT-1997-3443, has been undertaken to distinguish illegal use
      of zeranol from consumption of food contaminated with Fusarium spp. toxin. One of
      the tasks was development of screening and confirmatory methods of analysis. This
      paper describes a new method based on two-step clean-up and GC-MS analysis. The
      first clean-up step is matrix-dependant; the second is applicable to both urine
      and meat. The MS is operated in negative chemical ionisation mode. The method is
      quantitative for zeranol and taleranol, alpha- and beta-zearalenol, and
      zearalenone and qualitative for zearalanone. Validation was performed according
      to the latest EU performance criteria (Commission Decision 2002/657). For
      analysis of urine CC(alpha) and CC(beta) for the method (microg L(-1)) were 0.06
      0.11 for zeranol, 0.07-0.12 for taleranol, 0.07-0.11 for alpha-zearalenol, 0.21
      0.36 for beta-zearalenol, 0.35-0.60 for zearalenone, and 0.19-0.33 zearalanone.
      Within-laboratory reproducibility was 16.2, 11.2, 31.9, 30.1, 26.6, and 54.2% for
      zeranol, taleranol, alpha-zearalenol, beta-zearalenol, zearalenone, and
      zearalanone, respectively. It was found that all the compounds are stable in
      urine at -20 degrees C for at least a year. Part of the validation program was
      organisation of a small proficiency study (ringtest) and a correlation study with
      an LC-MS-MS method developed by the Veterinary Science Division (VSD; Belfast, UK
      NI). This study showed there was good correlation between results from both
      laboratories. The method can be used for quantitative analysis discriminating
      illegal use of zeranol from consumption of zearalenone-contaminated food.

PMID- 16416096
TI  - Eu3+-doped Gd2O3 nanoparticles as reporters for optical detection and
      visualization of antibodies patterned by microcontact printing.
AB  - Lanthanide oxide nanoparticles are promising luminescent probes in bioanalysis,
      because of their unique spectral properties, photostability, and low-cost
      synthesis. We report for the first time the application of europium-doped
      gadolinium oxide (Eu:Gd2O3) nanoparticles to the optical imaging of antibody
      micropatterns. The nanoparticles were synthesized by spray pyrolysis and coated
      with antibody (IgG) molecules by physical adsorption. Our experiments showed that
      the Eu:Gd2O3 is a good biocompatible solid support for antibody immobilization.
      The antibodies (anti-rabbit IgG) immobilized on the nanoparticles had excellent
      biological activity in the specific recognition reaction with rabbit IgG
      patterned in line strips (10 micromx10 microm) on a glass substrate by use of a
      micro-contact printing technique. The specific immunoreaction was confirmed by
      two independent microscopic techniques-fluorescence and scanning electron
      microscopy (SEM). Both microscopic images revealed that the nanoparticles were
      organized into designated structures as defined by the microcontact printing
      process with negligible non-specific binding. The nanoparticles can be used as
      fluorescent markers in a variety of immunosensing applications in a microscale
      format.

PMID- 16416097
TI  - SEM-FTIR spectroscopic evaluation of deterioration in an historic coffered
      ceiling.
AB  - Microorganisms generally degrade wood when moisture, oxygen and other
      environmental factors provide favorable growing conditions. Scanning electron
      microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to
      study the development and transformation of the products formed during the
      biomineralization process that follows the deterioration of wood from an
      historical coffered ceiling (Cloister of St Francesc (XIV century), Palma de
      Mallorca, Spain). After fungi colonization, cellulose and lignin disappear and
      inorganic salts are formed. Thus, the secretion of numerous acids (initially
      oxalic acid) by fungal hyphae also leads to the precipitation of authigenic
      salts. Damaged cells or tissues enhance the formation and growth of crystals,
      which is strongly favored by fungi that function as calcification nuclei.
      Finally, the presence of dihydrated calcium sulfate reveals the contribution of
      environmental factors to the weathering of wood.

PMID- 16416098
TI  - Phospholipids from some common fungi associated with damp building materials.
AB  - Methods for the analysis of fungal biomass in contaminated building materials
      have been limited to methods that use viable propagules as well as indicators of
      total biomass such as fungal glucan and ergosterol. Because of large differences
      in the survival times of spores, and limitations imposed by the use of agar media
      to assess fungal cells for the former approach, no quantitative information and
      poor qualitative information is obtained. The use of the biochemical indicators
      provides reliable quantitative information but no qualitative data. Analysis of
      phospholipids of various bacteria and, recently, of fungi common in outdoor air
      has provided both qualitative and quantitative data on their distributions in
      various substrates including in outdoor air samples. In this report, we provide
      new data on the signature lipids of some fungi common on moldy building
      materials. Using the LC/MS/MS analysis described, an estimate can be made of the
      fresh weight of fungal cells and the relative abundance of the common genera of
      fungi typically found on moldy materials.

PMID- 16416099
TI  - An immunoassay for a urinary metabolite as a biomarker of human exposure to the
      pyrethroid insecticide permethrin.
AB  - Permethrin is the most popular synthetic pyrethroid insecticide used in
      agriculture and public health. For the assessment of human exposure to
      permethrin, a competitive indirect enzyme-linked immunosorbent assay (ELISA) for
      the detection of the glycine conjugate of a major metabolite, cis-/trans-3-(2,2
      dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), of permethrin
      was developed based on a polyclonal antibody. An assay based on an antibody with
      a high sensitivity was optimized and characterized. The IC50 value and the
      detection range for trans-DCCA-glycine, in the assay buffer were 1.2 and 0.2-7.0
      microg/L, respectively. The antibody recognized trans-DCCA-glycine and the
      mixture of cis-/trans-DCCA-glycine with an isomer range from 30:70 to 50:50
      nearly equally. Little or no cross-reactivity to permethrin and its other free
      metabolites or glycine conjugates was measured. The integration of the ELISA and
      solid-phase extraction which was used to reduce the matrix effect from human
      urine samples provided for analysis of total cis-/trans-DCCA-glycine at low parts
      per billion levels in the samples. The limit of quantitation of the target
      analyte was 1.0 microg/L in urine with a limit of detection of 0.1 microg/L in
      buffer. This assay might be a useful tool for monitoring human exposure to
      permethrin.

PMID- 16416100
TI  - [Sex as a factor in pain studies of women 's accounts or pain after arthroscopy
      compared with men].

PMID- 16416101
TI  - [Unique children -- unique headaches. Case reports of pediatric headache patients
      from an outpatient children's pain department].
AB  - In the industrialized nations headache prevalence is increasing in children and
      adolescents. The nosologic classification determines the therapeutic strategy to
      follow. Three case reports illustrate the optimal cooperation of both a pediatric
      outpatient pain clinic and a pediatric psychosomatic pain clinic. We report on
      (1) a girl aged 2 years and 7 months with a 4-month history of headache episodes
      lasting about 15 min each with concomitant symptoms; (2) an 11-year-old boy with
      Schimmelpenning-Feuerstein-Mims syndrome, symptomatic focal epilepsy, psychomotor
      retardation, mild postinfectious internal hydrocephalus, and repeated heat
      triggered episodes of right-sided headache beginning suddenly with a duration of
      5-30 min and concomitant flush of his hemiface; and (3) a 12-year-old boy who for
      about 2 years has suffered from "migraine" 3 times a week, significantly
      impairing his quality of life. We discuss the patients' courses, diagnostic
      pitfalls, and therapeutic options. For the optimal treatment of children with
      headache not easily fitting into one of the categories, with significant
      comorbidity present, or if there is no adequate response to therapy conforming
      with guidelines, the help of an interdisciplinary pediatric pain clinic is
      invaluable.

PMID- 16416102
TI  - A comparison of two different intra-articular hyaluronan drugs and physical
      therapy in the management of knee osteoarthritis.
AB  - The aim of this study was to compare the effects of physical therapy agents (PTA)
      and two different intra-articular hyaluronan drugs (sodium hyaluronate (NaHA) and
      hylan G-F 20) on knee osteoarthritis (OA). The randomised, single-blind study,
      with 12 months of follow-up, was performed on 80 patients diagnosed as knee OA.
      The patients were randomly divided into two treatment groups: patients in group 1
      were given weekly intra-articular hyaluronan treatment which consisted of either
      hylan G-F 20 or NaHA during the first 3 weeks and in the sixth month; PTA was
      applied to each patient in group 2 five times a week for 3 weeks with a series of
      infrared, short-wave diathermy-pulsed patterns and interferential therapy.
      Clinical assessments for each patient were made at 1, 3, 6, 9 and 12 months using
      the following measures: spontaneous pain, pain at rest, pain at night, pain on
      touch, pain on movement, 15 m walking time, range of motion, short form 36 (SF
      36), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) global
      assessment. There was significant improvement in all variables measured in both
      groups during the follow-up except the WOMAC-stiffness and range of the motion.
      The improvement of pain (at night, at rest, SF-36) and SF-36 social functioning
      subscales was greater in the PTA group. Consequently, in the subgroup analyses,
      there was no difference between PTA and hylan groups for this improvement. In the
      comparison of two drugs, the reduction of pain on touch and WOMAC-function was
      greater in hylan group than that of NaHA. No serious local or systemic effects
      were observed following injections. Although all patients had improvement, PTA
      was superior to hyaluronan group for no activity-related pain and functional
      performance. On the other hand, this study supports the preferential use of hylan
      over NaHA in patients with knee OA.

PMID- 16416103
TI  - The role of the follow-up chest radiograph in suspected non-accidental injury.
AB  - BACKGROUND: Rib fractures in children under the age of 2 years have a strong
      correlation with non-accidental injury (NAI). Follow-up radiographs can improve
      detection. OBJECTIVE: To evaluate the value of the follow-up chest radiograph in
      suspected non-accidental injury. MATERIALS AND METHODS: The study included all
      children less than 2 years of age who were investigated for suspected NAI in our
      institution between January 1998 and October 2003. Prior to January 2000, only
      selected patients were asked to attend for a follow-up chest radiograph. From
      January 2000 onwards all children were asked to reattend. RESULTS: Of 200
      children included in the study, 59 (29.5%) reattended for a follow-up chest
      radiograph. The follow-up film provided useful additional information in 7 (12%)
      of the 59 children. In two children rib fractures were noted only on the follow
      up chest radiograph. In a further two patients additional rib fractures were
      noted. Additional dating information was obtained for two patients. For one child
      both additional fractures and dating information were noted. CONCLUSIONS: The
      follow-up chest radiograph provides useful information in children with suspected
      NAI and it is recommended that it should be included routinely in the imaging
      investigations of these children.

PMID- 16416104
TI  - Diagnosis of perfusion abnormality of the pulmonary artery in Takayasu's
      arteritis using contrast-enhanced MR perfusion imaging.
AB  - To determine the clinical efficacy of contrast-enhanced magnetic resonance (MR)
      perfusion imaging in the diagnosis of perfusion abnormality in the pulmonary
      artery (PA) in Takayasu's arteritis (TA). Twenty-one patients were evaluated.
      Pulmonary MR perfusion images were acquired using a 2-dimensional (2D) fast
      spoiled gradient echo sequence with single-slice technique (TR/TE, 5.3/1.3; flip
      angle, 30 degrees; receiver bandwidth, 31.2 kHz/pixel; acquisition time, 0.7 s;
      and total acquisition time, 49 s). Seventy continuous subtracted MR images were
      evaluated, and the presence of perfusion abnormality was determined in lobe-based
      (n=126) and patient-based (n=21) analyses. Sensitivity, specificity, positive
      predictive value (PPV), and negative predictive values (NPV) were calculated
      using perfusion scintigraphy as a standard reference. For lobe-based analysis,
      sensitivity was 91.7-95.8%, specificity was 92.2-93.7%, and PPV and NPV were 73.3
      76.7% and 97.9-99.0%, respectively. For patient-based analyses, sensitivity was
      100%, specificity was 72.7%, and PPV and NPV were 76.9% and 100%, respectively.
      Kappa values for each analysis were between 0.78-1.00. In conclusion, MR
      perfusion imaging appears to be a valuable, noninvasive method to estimate PA
      involvement in patients with TA.

PMID- 16416106
TI  - Spatial encoding by bumblebees (Bombus impatiens) of a reward within an
      artificial flower array.
AB  - We presented bumblebees a spatial memory task similar to that used with other
      species (e.g., cats, dogs, and pigeons). In some conditions we allowed for
      presence of scent marks in addition to placing local and global spatial cues in
      conflict. Bumblebees (Bombus impatiens) were presented an array of artificial
      flowers within a flight cage, one flower offering reward (S+), while the others
      were empty (S-). Bees were tested with empty flowers. In Experiment 1, flowers
      were either moved at the time of testing or not. Bees returned to the flower in
      the same absolute position of the S+ (the flower-array-independent (FAI)
      position), even if it was in the wrong position relative to the S- and even when
      new flower covers prevented the use of possible scent marks. New flower covers
      (i.e., without possible scent marks) had the effect of lowering the frequency of
      probing behavior. In Experiment 2, the colony was moved between training and
      testing. Again, bees chose the flower in the FAI position of the S+, and not the
      flower that would be chosen using strictly memory for a flight vector. Together,
      these experiments show that to locate the S+ bees did not rely on scent marks nor
      the positions of the S-, though the S- were prominent objects close to the goal.
      Also, bees selected environmental features to remember the position of the S+
      instead of relying upon a purely egocentric point of view. Similarities with
      honeybees and vertebrates are discussed, as well as possible encoding mechanisms.

PMID- 16416105
TI  - Modern cross-sectional imaging in the diagnosis and follow-up of intracranial
      aneurysms.
AB  - Digital subtraction angiography (DSA) is still considered the gold standard for
      most applications in neurovascular imaging. However, with the ongoing development
      of cross-sectional imaging modalities DSA is increasingly being replaced by less
      invasive methods. This contribution describes the diagnostic value and the
      increasing potential of computed tomography angiography (CTA) and magnetic
      resonance angiography (MRA) in the diagnosis and follow-up of intracranial
      aneurysms. The main role of CTA is in the diagnosis and therapy planning of
      ruptured aneurysms; in contrast, MRA plays an increasingly important role in the
      screening for asymptomatic aneurysms (especially in cases of familial
      subarachnoid hemorrhage) and in the follow-up after endovascular therapy with
      coils and/or intracranial stents. Technical issues concerning examination
      technique are covered here as well as an approach to advanced postprocessing of
      the image data. Furthermore, a brief outlook on the impact of new developments
      (MRA with parallel imaging and at 3.0 T) is given.

PMID- 16416109
TI  - [Research on health care for the elderly. Prevention, case management, and care
      for patients with dementia].
AB  - Three examples serve to highlight challenges for health care that stem from
      population ageing and the health situation of the elderly. The first challenge is
      to develop and evaluate prevention and health promotion programmes for the
      elderly. Two promising interventions are outlined: 'preventive home visits' and
      'active health promotion in old age'. The second challenge is to improve the
      coordination of health and social care measures. Case management is presented as
      one adequate approach in this regard. The third challenge stems from the
      increasing prevalence of age-specific diseases. In terms of dementia it is
      pointed out that it is important to improve early diagnosis and to integrate self
      help groups and counselling services into therapy.

PMID- 16416107
TI  - Short-term monitoring of cognitive functions before and during the first course
      of treatment.
AB  - PURPOSE: Side effects of chemotherapy on cognitive functions in older patients
      have rarely been investigated. Addressing this lack of research, the present
      study evaluated cognitive functions in older cancer patients. METHODS: A total of
      130 younger (n=59; age<60) and older (n=71; age>or=60) cancer patients with
      hematological disease or cancer of the intestinal tract took part in the study.
      To explore short-term effects of chemotherapy, a group of patients assessed
      before the start of chemotherapy was compared with patients who already received
      their first course of chemotherapy. RESULTS: Cognitive impairments of verbal
      learning, word fluency, and memory were observed following the first few days
      after treatment onset. Older patients showed stronger memory impairments after
      start of chemotherapy than younger cancer patients. Additionally, depression was
      neither associated with short-term effect of chemotherapy nor with age.
      CONCLUSIONS: The results suggest that chemotherapy has negative short-term
      effects on some cognitive functions. But age-dependent effects were only found
      for memory.

PMID- 16416110
TI  - [Health services research in surgery: the example of breast cancer surgery].
AB  - The epidemiological relevance of breast cancer in Germany has led to a number of
      initiatives actually changing the processes and structures of care. The ultimate
      aim of health services research in surgery is to evaluate the impact of these
      initiatives on the effectiveness and efficiency of the respective health care
      services. Results of international studies show for instance breast-conserving
      therapy to be related to the patients' socioeconomic status. In addition, breast
      specialists tend to operate more in adherence to practice guidelines and to
      implement new procedures like sentinel lymph node biopsies earlier. Preliminary
      results from Germany also demonstrate a considerable practice variation in breast
      cancer surgery. Causes and effects of such variation still have to be explored.
      For that purpose, newly available data sources on health care services in
      relation to breast cancer surgery in Germany could be used. The inherent
      challenge is to combine data from tumour registries, statutory comparative
      quality assurance activities and inpatient remuneration via DRGs for health
      services research in surgery.

PMID- 16416108
TI  - Tumor-associated carbonic anhydrases are linked to metastases in primary cervical
      cancer.
AB  - PURPOSE: Carbonic anhydrase IX (CA9) has emerged as an important surrogate marker
      for hypoxia in solid tumors. CA12 shares a role with CA9 in acidification of
      micromilieu but it is less strictly regulated by hypoxia than CA9. In this study,
      we investigated expression of CA9 and CA12 mRNA in primary cervical cancer. We
      also examined whether CA9 expression can be an indicator of reoxygenation of
      tumor by measuring its mRNA expression during fractionated radiotherapy. METHODS:
      Tumor tissues were obtained from 59 patients with uterine cervical cancer who
      underwent radiotherapy, and a second biopsy was taken after patients had received
      either 10 or 20 Gy of radiation. The follow-up period ranged from 2.4 to 75
      months (median=23 months). The ratio of CA9 and beta-actin mRNA expression was
      determined both pre- and during radiation treatment by RT-PCR. RESULTS: CA9 and
      CA12 mRNA expression was detected in 62.7 and 88.1% of tumors (i.e. patients),
      respectively, and co-expression was observed in 61% of patients. Multivariate
      analysis revealed that CA9 expression was the most significant factor associated
      with metastasis-free survival (P=0.008, hazard ratio 34.8), whereas CA12 mRNA
      expression was linked to a lower risk of metastasis (P=0.007, hazard ratio of
      0.07). Tumor CA9 expression was not altered following either 10 or 20 Gy of
      radiotherapy. CONCLUSION: The strong correlation between CA9 expression and
      metastasis suggests that CA9 expression might be an important indicator for
      identifying patients who require more aggressive systemic therapy.

PMID- 16416111
TI  - Family history may be misleading in the diagnosis of Dent's disease.
AB  - The rare Dent's disease manifests with medullary nephrocalcinosis,
      nephrolithiasis, hypercalciuria, low molecular weight proteinuria and other
      tubular dysfunctions, rickets or osteomalacia, and renal failure, in various
      combinations. It is a recessive X-linked condition. Clinicians consider family
      history a fundamental pointer to its diagnosis, but this is not invariably the
      case as clearly pointed out by the two reported cases.

PMID- 16416112
TI  - In vitro calcium oxalate crystallisation methods.
AB  - In vitro calcium oxalate crystallisation has been, and will continue to be, of
      fundamental importance to urolithiasis research. Many different methods have been
      employed which differ qualitatively and quantitatively in the extent that they
      reproduce aspects of the renal system or in their ability to distinguish
      different aspects of crystallisation activity. Whatever system is used there are
      three key aspects that are worth bearing in mind. Firstly, a major controlling
      factor will be the prevailing supersaturation and other physicochemical
      considerations, secondly, during the course of the reaction different processes
      may come into play and thirdly, the processes we are trying to model take place
      in a dynamic biological environment. Different approaches to the study of
      crystallisation can be classified in many ways, such as the process or analytical
      technique but at a more fundamental level it is helpful to focus on the changes
      in supersaturation during the course of the reaction. A steady state
      supersaturation is more likely to be representative of the intra-renal situation
      than a system which decays to the equilibrium position. The constant composition
      method and the mixed suspension mixed product removal method both achieve a
      steady supersaturation.

PMID- 16416113
TI  - Lithiasis in cystic kidney disease and malformations of the urinary tract.
AB  - The prevalence of renal stones in renal cystic and malformative conditions
      exceeds the prevalence of renal stones in the general population, suggesting that
      the above-mentioned cystic and malformative disorders favor stone formation.
      Urinary stasis is generally assumed to play a major part in the pathogenesis of
      the nephrolithiasis associated with distorted renal anatomy due to a delayed
      washout of crystals and risk of urinary infections. However metabolic factors are
      also important in the pathogenesis of stones in these conditions. Indeed,
      metabolic abnormalities have been observed in the majority of stone-forming
      patients with conditions such as horseshoe kidney and ureteropelvic junction
      obstruction. Five different models of stone formation can be identified,
      depending on stone composition, risk of infection stones, and pathogenesis of
      renal cystic and malformative conditions. A proper metabolic evaluation should be
      conducted to diagnose specific, treatable metabolic disorders, thereby reducing
      the frequency of recurrent stone disease in these conditions as well.

PMID- 16416115
TI  - Plasma cell leukemia: a rare condition.
AB  - Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized
      by a malignant proliferation of plasma cells in the bone marrow and peripheral
      blood. PCL is also characterized by a fulminant course and poor prognosis.
      Diagnosis of PCL is established based on Kyle's criteria which include an
      absolute plasma cell number comprising greater than 20% of peripheral blood
      cells. PCL has two variants: the primary form presents de novo in patients with
      no previous history of multiple myeloma (MM) and the secondary form consists of a
      leukemic transformation in a previously recognized MM. In this paper, we report
      ten cases of PCL occurring since 1994 to 2005 in a Mexican health institution.
      Median age at presentation in our study was 58 years, most of them were female
      (70%). Primary PCL (PPCL) represented 80% and secondary PCL (SPCL) 20%. We
      describe clinical characteristics, stage, and response to treatment.
      Interestingly, we report a patient who presented a secondary PCL and acquired
      activated protein C resistance (APC-R). Additionally, we found an incidence of
      20% of venous thrombosis events in two patients with PPCL. Mean survival was 5.9
      months (range 2-17) for both PPCL and SPCL. Mean survival for PPCL was 6.75
      months and for SPCL 2.0 months, similar to previous literature reports.

PMID- 16416114
TI  - Addition of cyclosporin-A to chemotherapy in secondary (post-MDS) AML in the
      elderly. A multicenter randomized trial of the Leukemia Working Group of the
      Hellenic Society of Hematology.
AB  - In elderly patients with secondary leukemia, poor therapeutic response and low
      overall survival have been attributed mainly to age and to the primary resistance
      of leukemic cells to chemotherapy. Modulation of resistance has been attempted in
      different studies, but the results have been contradictory. We conducted an open,
      randomized multicenter clinical trial involving patients more than 60 years old
      with secondary leukemia preceded by a myelodysplastic syndrome. The induction
      chemotherapy regimen included idarubicin, cytarabine, and etoposide (group A);
      randomization involved simultaneous administration of cyclosporin-A per os (group
      B). Fifty-five patients were evaluated, 26 in group A and 29 in group B. Overall
      complete remission was achieved in 40% of the patients, 27% vs 52% in groups A
      and B, respectively (p=0.01). Leukemia-free survival was more favorable in
      patients who received cyclosporin-A, 12 vs 7 months for groups B and A,
      respectively (p=0.03). In a follow up period of 30 months, 7 out of 55 patients
      (13%) were alive, 4 of whom were in complete remission. Five out of the 7 alive
      patients were randomized in group B and had received cyclosporin-A. Treatment
      failure was higher in group A [19 of 26 patients (73%)] than in group B with CsA
      [14 of 29 patients (48%)] (p<0.0001). Treatment-related toxicity/mortality was
      13%. Modulation of drug resistance by CsA in elderly people suffering from
      secondary acute leukemia may improve the outcome of chemotherapy without
      increasing drug toxicity and treatment-related mortality.

PMID- 16416116
TI  - Taenia solium cysticerci synthesize androgens and estrogens in vitro.
AB  - Cysticerci from Taenia solium develop in the pig muscle and cause severe diseases
      in humans. Here we report on the capacity of T. solium cysticerci to synthesize
      sex steroid hormones. T. solium cysticerci were dissected from infected pork
      meat. Parasites were incubated for different periods in culture media plus
      antibiotics and tritiated steroid precursors. Blanks and parasite culture media
      were extracted and analyzed by thin-layer chromatography (TLC) in two different
      solvent systems. In some experiments, the scoleces were incubated separately.
      Results showed that T. solium cysticerci transform [(3)H]androstenedione to
      [(3)H]testosterone in a time-dependent manner. The production was confirmed in
      two different solvent systems. The incubation with [(3)H]testosterone yielded
      only small amounts of [(3)H]androstenedione. The recrystallization procedure
      further demonstrated that the metabolite identified by TLC was testosterone. The
      isolated scoleces incubated in the presence of [(3)H]androstenedione yielded
      [(3)H]testosterone and small quantities of [(3)H]17beta-estradiol. The results
      reported here demonstrate that T. solium cysticerci have the capacity to
      synthesize steroid hormones.

PMID- 16416117
TI  - Light and transmission electron microscopic studies of a haemogregarine in
      naturally infected fan-footed gecko (Ptyodactylus hasselquistii).
AB  - The present study focuses on and describes the developmental stages of a
      haemogregarine species in the blood and tissues of the gecko Ptyodactylus
      hasselquistii. The blood stages were differentiated into two forms: a short
      gamont measuring 11.87 x 6.42 microm and a banana-shaped mature gamont measuring
      14.13 x 10.03 microm in length and width, respectively. Both erythrocytes and
      leucocytes had been invaded. The parasitaemia level is up to 410 per 10,000
      erythrocytes counted. The gamont has a karyolytic effect on the host cell
      nucleus. Merogony occurred in the parenchyma cells of liver and the endothelial
      cells of the lung. The meronts in the lung were found in two forms: the
      micromeront measured 14.93x13.14 microm and produced a few numbers (average 4) of
      macromerozoites. The macromeront measured 26.3 x 16 microm and produced more
      small-sized merozoites (average 11.5), or micromerozoites. On the ultrastructural
      level, merozoites have a pellicle, which consists of an outer and inner membrane.
      The merozoites are nearly identical to the blood stages of the parasite.

PMID- 16416118
TI  - Cercarial production of Fascioloides magna in the snail Galba truncatula
      (Gastropoda: Lymnaeidae).
AB  - Single-miracidium infections of Fascioloides magna in two populations of Galba
      truncatula were carried out under laboratory conditions to count free rediae and
      cercariae in snail cadavers just after death. Cercaria-shedding snails were in
      low numbers, and their shell height at day 60 p.e. was significantly greater than
      that of numerous infected snails that died without cercarial shedding. In snails
      that died between days 44 and 60 p.e. (at 20 degrees C), the numbers of second
      generation rediae significantly increased with increasing shell heights of
      infected snails. First-generation rediae showed insignificant, quantitative
      variations, while scarce rediae of the third generation were only found in the
      highest snails. Cercariae were only produced by the second redial generation. In
      both groups of snails, free cercariae appeared from 6 mm of shell height, and
      their numbers increased in the upper classes up to 32.9 per snail. Metacercariae
      were only found from 9 mm of shell height and were in low numbers. The global
      cercarial production ranged from 163.5 to 210.0 in the highest classes of snail
      size from both groups and was limited, whereas the mean burdens of free rediae
      fluctuated from 39.5 to 43.9. The death of numerous infected snails without
      cercarial shedding might be explained by the presence of a very high number of
      second-generation rediae simultaneously growing within the body of these snails.

PMID- 16416119
TI  - Random amplified polymorphic DNA profiles of Trypanosoma cruzi isolates from
      chagasic patients with different clinical forms.
AB  - The genetic variability of 61 Trypanosoma cruzi isolates from 47 chronic chagasic
      patients of Minas Gerais state was analyzed by random amplified polymorphic DNA
      polymerase chain reaction (RAPD-PCR) using M13-40, lambdagt11-F, and L15996
      primers. Cluster analysis by unweighted pair group method analysis was applied to
      RAPD profiles, and cluster analysis used to verify a possible correlation among
      different clinical forms of the disease from these patients. The T. cruzi
      isolates showed distinct grouping on tree topology, with the isolates not being
      possible to establish a correlation to the clinical forms of Chagas' disease.
      These data showed that the T. cruzi isolates from these patients would compose a
      group of populations well correlated genetically.

PMID- 16416121
TI  - Effect of artificial gastrointestinal fluids on the excystation and metacystic
      development of Entamoeba invadens.
AB  - The effect of artificial gastric fluid (AGF), containing 0.5% pepsin and 0.6%
      hydrochloric acid, pH 1.8, in distilled water, on the excystation and metacystic
      development of Entamoeba invadens was examined. Excystation, which was assessed
      by counting the number of metacystic amoebae after inducing excystation, was
      enhanced by pretreatment of cysts with AGF for 30 to 60 min at 37 degrees C but
      not 26 degrees C. Longer exposure of cysts to AGF significantly reduced their
      viability. Significant enhancement of excystation was observed by pretreatment of
      cysts with distilled water only at 37 degrees C. In addition, 0.6% hydrochloric
      acid had a comparable enhancing effect on excystation to AGF. Metacystic
      development, when determined by the number of nuclei in amoeba, was slightly
      enhanced by pretreatment with AGF. An artificial intestinal fluid (AIF),
      containing 1% pancreatin, 1% sodium bicarbonate, and 5% ox bile, pH 8.0, in
      distilled water, had a significant toxic effect on cysts, where 1% pancreatin had
      neither an enhancing effect on excystation nor a toxic effect on cysts, whereas
      5% ox bile had a toxic effect on cysts. Pretreatment of cysts with AGF followed
      by AIF had a similar toxic effect on cysts to that by AIF only. These results
      suggest that gastric fluid but not intestinal fluid at 37 degrees C contributes
      to enhancing excystation for Entamoeba infection.

PMID- 16416120
TI  - The putative telomerase reverse transcriptase component of Leishmania
      amazonensis: gene cloning and characterization.
AB  - The Leishmania amazonensis telomerase gene was cloned by a polymerase chain
      reaction-based strategy using primers designed from a Leishmania major sequence
      that shared similarities with conserved telomerase motifs. The genes from three
      other species were cloned for comparative purposes. A ClustalW multiple-sequence
      alignment demonstrated that the Leishmania telomerases show greater homology with
      each other than with the proteins of other kinetoplastids and eukaryotes.
      Characterization experiments indicated that the putative Leishmania telomerase
      gene was probably in single copy and located in the largest chromosomes. A single
      messenger ribonucleic acid transcript was found in promastigotes. Phylogenetic
      analysis suggested that Leishmania telomerase might represent a liaison between
      the oldest and the newest branches of telomerases.

PMID- 16416122
TI  - Patterns in the distribution of avian lice (Phthiraptera: Amblycera, Ischnocera)
      living on the great grey shrike Lanius excubitor.
AB  - The lice parasite community of great grey shrike Lanius excubitor collected in NE
      Slovakia during 1962-1974 was quantitatively studied. Lice fauna comprised of
      three species: Docophorulus coarctatus, Bruelia cruciata (Ischnocera) and
      Lanicanthus camelinus (Amblycera). All these species were previously indicated as
      characteristic for that host. The prevalence of lice was high--lice were
      recovered from 96.3% (n=108) host specimens. Distributions of lice on the great
      grey shrike, a strictly territorial bird, were aggregated, indicating substantial
      variation in the abundance of lice. Sex ratios of lice were biased towards
      females and not correlated with the subpopulation size of lice on individual
      hosts.

PMID- 16416123
TI  - Malaria in a holoendemic area of Burkina Faso: a cross-sectional study.
AB  - A malaria survey of the entire population of a village in Western Burkina Faso
      (n=1,561) was conducted to assess malaria endemicity. The study population was
      examined for symptoms characteristic of malaria including fever, anaemia,
      splenomegaly and parasites present in thick blood films. In the overall study
      population, the prevalence of Plasmodium spp. infection by microscopic
      examination of thick blood films was 79.0% (1,233/1,561). In a subcohort with 201
      individuals, PCR techniques found a prevalence rate for all Plasmodium spp. of
      92.0% (185/201), while microscopy found one of 80.6% (162/201). A combination of
      both methods gives a rate of 95.5% (192/201). Though univariate logistic analyses
      of elevated body temperature, anaemia, splenomegaly and age showed them all to be
      predictors of or risk factors for an infection, only elevated body temperature
      and age were predictors in multivariate logistic analysis. However, the symptom
      of splenomegaly did show a highly significant association with infection by
      multiple species of Plasmodium.

PMID- 16416124
TI  - Eprinomectin in dairy zebu Gobra cattle (Bos indicus): plasma kinetics and
      excretion in milk.
AB  - The pharmacokinetics and mammary excretion of eprinomectin were determined in
      zebu Gobra following topical administration of 0.5 mg kg(-1). The kinetics of
      plasma and milk was analysed using a one-compartment model. The maximum plasma
      concentration of 8.83+/-2.15 ng ml(-1) occurred 1.30 days post-administration.
      The area under the plasma concentration-time curve was 30.63+/-5.56 ng day(-1)
      ml(-1) and the mean residence time was 3.38+/-0.60 days. Eprinomectin was
      detected in milk at the first sampling time and thereafter for at least 8 days.
      The systemic availability of eprinomectin was significantly lower than that for
      other breeds of cattle. Comparison of the milk and plasma data demonstrated the
      parallel disposition of the drug in the milk and plasma with a milk/plasma ratio
      of 0.094. The very low extent of mammary excretion supports the permitted use of
      eprinomectin in lactating zebu Gobra.

PMID- 16416125
TI  - Surface ultrastructure of the puparia of the blow fly, Lucilia cuprina (Diptera:
      Calliphoridae), and flesh fly, Liosarcophaga dux (Diptera: Sarcophagidae).
AB  - Surface ultrastructure of the puparia of the blow fly, Lucilia cuprina, and flesh
      fly, Liosarcophaga dux, are presented utilizing scanning electron microscopy
      (SEM). Emphasis was focused on characteristic features of the puparia that could
      be used for differentiation from other forensically important fly species. The
      puparium of L. cuprina typically measures 6.2+/-0.2 mm in length and 2.3+/-0.1 mm
      in width. Each anterior spiracle contains a single row of 5-7 papillae. The
      intersegmental spines between the prothorax and mesothorax are triangular with
      constricted tips. A clustered bubble membrane, comprising about 30 mammillate
      structures, is positioned dorsolaterally on each side of the first abdominal
      segment in young puparia but is replaced by short, tubular respiratory horns in
      aged puparia. The posterior end of the puparium is broadly truncate and bears a
      pair of medially positioned posterior spiracles that each contains three straight
      spiracular slits. The puparium of L. dux is larger in comparison to L. cuprina
      and typically measures 9.9+/-0.3 mm in length and 3.8+/-0.2 mm in width. An
      anterior spiracle of this species contains 14-17 papillae. The intersegmental
      spines between the prothorax and mesothorax are broad and triangular. A
      convoluted structure of unknown function was observed at the dorsolateral edge of
      segments 5-11. In L. dux, the caudal segment of the puparium is slightly tapered
      and abruptly truncated and contains a pair of posterior spiracles that are
      located within a deep concavity in the terminal end. Each posterior spiracular
      disc appears D-shaped, with a pronounced medial projection and three vertically
      oriented long, narrow spiracular slits. The anatomical features presented herein
      may be useful for identification of fly puparia of these two species in future
      forensic entomological investigations.

PMID- 16416126
TI  - Ultrastructure of adhesive device in fly in families calliphoridae, muscidae and
      sarcophagidae, and their implication as mechanical carriers of pathogens.
AB  - The ultrastructure of adhesive device or the pulvilli, pad-like structure between
      the tarsal claws of the legs, is presented in the blowfly (Calliphoridae),
      housefly and relatives (Muscidae), and flesh fly (Sarcophagidae) through scanning
      electron microscopy. The blowfly species were Chrysomya chani, Chrysomya
      nigripes, Chrysomya pinguis, and Chrysomya villeneuvi; while those of the
      housefly and relatives were Musca domestica and Hydrotaea chalcogaster,
      respectively. Fresh fly species included Boettcherisca peregrina and
      Liosarcophaga dux. Numerous tenent setae were observed on the ventral side of the
      pulvilli. Two features of the tip of the tenent setae were found as a spatula
      like (in C. chani, C. pinguis, C. nigripes, M. domestica, H. chalcogaster, B.
      peregrina, and L. dux) and spoon-like tip (in C. villeneuvi). Transmission
      electron microscopy of the tenent setae in M. domestica revealed the electron
      lucent centrally located, suggesting an adhesive substance. These results
      provided anatomical information that allow us to not only understand the
      successful attachment of flies to smooth surfaces but also clarify their role as
      a mechanical carrier of microorganisms.

PMID- 16416127
TI  - Effect of glucose limitation and specific mutations in the module 5 enoyl
      reductase domains in the nystatin and amphotericin polyketide synthases on
      polyene macrolide biosynthesis.
AB  - Enoyl reductase (ER) domains in module 5 of nystatin and amphotericin polyketide
      synthase (PKS) are responsible for reduction of the C28-C29 unsaturated bond on
      the nascent polyketide chain during biosynthesis of both macrolides, resulting in
      production of tetraenes nystatin A(1) and amphotericin A, respectively. Data
      obtained in fermentations under glucose limitation conditions demonstrated that
      the efficiency of the ER5 domain can be influenced by carbon source availability
      in the amphotericin producer Streptomyces nodosus, but not in the nystatin
      producer Streptomyces noursei. Two S. noursei ER5 domain mutants were
      constructed, GG5073SP and S5016N, both producing the heptaene nystatin analogue
      S44HP with unsaturated C28-C29 bond. While the GG5073SP mutant, with altered ER5
      NADPH binding site, produced S44HP exclusively, the S5016N mutant synthesized a
      mixture of nystatin and S44HP. Comparative studies on the S5016N S. noursei
      mutant and S. nodosus, both producing mixtures of tetraenes and heptaenes,
      revealed that the ratio between these two types of metabolites was significantly
      more affected by glucose limitation in S. nodosus. These data suggest that
      mutation S5016N in NysC "locks" the ER5 domain in a state of intermediate
      activity which, in contrast to the ER5 domain in the amphotericin PKS, is not
      significantly influenced by physiological conditions.

PMID- 16416128
TI  - Molecular characterisation of ABC transporter type FtsE and FtsX proteins of
      Mycobacterium tuberculosis.
AB  - Elicitation of drug resistance and various survival strategies inside host
      macrophages have been the hallmarks of Mycobacterium tuberculosis as a successful
      pathogen. ATP Binding Cassette (ABC) transporter type proteins are known to be
      involved in the efflux of drugs in bacterial and mammalian systems. FtsE, an ABC
      transporter type protein, in association with the integral membrane protein FtsX,
      is involved in the assembly of potassium ion transport proteins and probably of
      cell division proteins as well, both of which being relevant to tubercle
      bacillus. In this study, we cloned ftsE gene of M. tuberculosis, overexpressed
      and purified. The recombinant MtFtsE-6xHis protein and the native MtFtsE protein
      were found localized on the membrane of E. coli and M. tuberculosis cells,
      respectively. MtFtsE-6xHis protein showed ATP binding in vitro, for which the K42
      residue in the Walker A motif was found essential. While MtFtsE-6xHis protein
      could partially complement growth defect of E. coli ftsE temperature-sensitive
      strain MFT1181, co-expression of MtFtsE and MtFtsX efficiently complemented the
      growth defect, indicating that the MtFtsE and MtFtsX proteins might be performing
      an associated function. MtFtsE and MtFtsX-6xHis proteins were found to exist as a
      complex on the membrane of E. coli cells co-expressing the two proteins.

PMID- 16416130
TI  - Effect of previous argon laser trabeculoplasty on the ocular hypotensive action
      of latanoprost.
AB  - PURPOSE: To study the effect of previous argon laser trabeculoplasty (ALT) on the
      hypotensive activity of latanoprost in primary open-angle glaucoma (POAG).
      METHODS: This was a prospective, observer-masked study. We measured the
      intraocular pressure (IOP) before and after 3 months of monotherapy with
      latanoprost in 43 eyes that had undergone a previous ALT, and in a control group
      (not treated with ALT) of 43 IOP-matched eyes with POAG. RESULTS: Latanoprost
      induced a 17.4+/-16.6% IOP decrease in the study group (ALT-treated eyes) and a
      25.8+/-17.2% IOP reduction in the control eyes (P=0.02, unpaired Student's t
      test). CONCLUSIONS: Latanoprost is less effective in ALT-treated eyes than in
      eyes with POAG not treated with ALT.

PMID- 16416132
TI  - Adverse neonatal outcome after maternal biliopancreatic diversion operation:
      report of nine cases.

PMID- 16416131
TI  - Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: a case
      report.
AB  - A 44-day-old male infant with familial hemophagocytic lymphohistiocytosis (FHL)
      associated with the MUNC13-4 mutation is reported. He presented with fever and
      poor feeding, lymphocytosis with thrombocytopenia and CSF pleocytosis without
      virological explanation. On the basis of progressive hyperferritinemia (1323
      ng/ml), anemia (hemoglobin: 5.2 g/dl), hypertriglyceridemia (547 mg/dl) and
      increased LDH (1063 IU/l) with hemophagocytosis in the bone marrow,
      hemophagocytic lymphohistiocytosis was diagnosed. He showed a good response to
      corticosteroid therapy and the disease was stable for more than 5 months.
      Thereafter, he suffered from central nervous system complications, and
      successfully underwent unrelated cord blood stem cell transplantation. A
      remission was observed for more than 2 years, with mild mental retardation.
      Genetic analysis revealed that he had a compound heterozygous mutation of MUNC13
      4; namely a novel 2163G>A mutation resulting in W721X, and 754-1G>C resulting in
      a premature stop codon in this gene. Western blot analysis showed the complete
      loss of the MUNC13-4 protein, whereas other molecules associated with the SNARE
      systems were detected at normal levels. Conclusion. FHL may have a broad clinical
      spectrum, and further analysis on its phenotype-genotype association is required
      to establish an appropriate treatment strategy, including immunochemotherapy and
      stem cell transplantation in the future.

PMID- 16416133
TI  - CDG: a new case of a combined defect in the biosynthesis of N- and O-glycans.

PMID- 16416134
TI  - Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with
      locally advanced rectal cancer previously treated by preoperative
      radiochemotherapy and curative tumor resection.
AB  - BACKGROUND AND AIMS: The role of postoperative adjuvant chemotherapy in patients
      with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and
      curative surgery is still poorly investigated. PATIENTS AND METHODS: We pooled
      data from both arms of a phase III trial in which patients with locally advanced
      (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with
      pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were
      scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic
      acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5).
      Reasons preventing initiation of chemotherapy and treatment-related toxicities
      were evaluated. Patients' characteristics and survival parameters were compared
      between the treated and untreated patient groups. RESULTS: Out of 93 patients, 73
      (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to
      perioperative complications and refusal. Chemotherapy-related toxicities were
      mild to moderate in most cases, but--together with protracted postoperative
      complications--prevented the intended dose escalation of 5-FU in 71% of patients.
      Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the
      chemotherapy group, although there was a negative selection of patients with
      unfavourable characteristics into the untreated patient group.
      INTERPRETATION/CONCLUSION: Adjuvant chemotherapy using FA and 5-FU can be safely
      applied to the majority of patients with rectal cancer pretreated by RCT and
      surgery. Survival data are not suitable to allow far-reaching conclusions, but
      are in line with suggestions of a favourable effect of adjuvant chemotherapy in
      these patients.

PMID- 16416135
TI  - Prospective casemix-based funding, analysis and financial impact of cost outliers
      in all-patient refined diagnosis related groups in three Belgian general
      hospitals.
AB  - This study examined the impact of cost outliers in term of hospital resources
      consumption, the financial impact of the outliers under the Belgium casemix-based
      system, and the validity of two "proxies" for costs: length of stay and charges.
      The cost of all hospital stays at three Belgian general hospitals were calculated
      for the year 2001. High resource use outliers were selected according to the
      following rule: 75th percentile +1.5 xinter-quartile range. The frequency of cost
      outliers varied from 7% to 8% across hospitals. Explanatory factors were: major
      or extreme severity of illness, longer length of stay, and intensive care unit
      stay. Cost outliers account for 22-30% of hospital costs. One-third of length-of
      stay outliers are not cost outliers, and nearly one-quarter of charges outliers
      are not cost outliers. The current funding system in Belgium does not penalize
      hospitals having a high percentage of outliers. The billing generated by these
      patients largely compensates for costs generated. Length of stay and charges are
      not a good approximation to select cost outliers.

PMID- 16416136
TI  - ParaHox gene expression in the polychaete annelid Capitella sp. I.
AB  - Hox and ParaHox genes are transcriptional regulators vital for many aspects of
      embryonic development in bilaterian animals and are considered to have originated
      from one ancestral proto-Hox/ParaHox cluster. Hox genes are clustered in the
      genome of both protostomes and deuterostomes, and there is a specific
      relationship between the position of a gene in the cluster and the position of
      its expression along the animal body axis (colinearity). It is not clear whether
      the ParaHox genes Gsx, Xlox, and, Cdx generally exhibit a similar phenomenon
      since developmental expression for all three ParaHox genes within a single
      species has not yet been described for any protostome animal. Here we show the
      spatial and temporal localization for all three ParaHox genes in the polychaete
      Capitella sp. I, a member of one of the morphologically most diverse and
      understudied groups within the Metazoa, the Lophotrochozoa. Our data demonstrate
      that although both CapI-Xlox and CapI-Cdx are regionally expressed in the gut,
      the three Capitella sp. I ParaHox genes as a group do not perfectly fit
      predictions of temporal or spatial colinearity. Instead, there is a conservation
      of expression across species associated with development of particular tissues,
      and the relative order of initiation of ParaHox gene expression likely reflects
      the relative order of species-specific tissue development during ontogenesis.

PMID- 16416137
TI  - Gastrulation in the sea anemone Nematostella vectensis occurs by invagination and
      immigration: an ultrastructural study.
AB  - The sea anemone Nematostella vectensis has recently been established as a new
      model system for the understanding of the evolution of developmental processes.
      In particular, the evolutionary origin of gastrulation and its molecular
      regulation are the subject of intense investigation. However, while molecular
      data are rapidly accumulating, no detailed morphological data exist describing
      the process of gastrulation. Here, we carried out an ultrastructural study of
      different stages of gastrulation in Nematostella using transmission electron
      microscope and scanning electron microscopy techniques. We show that presumptive
      endodermal cells undergo a change in cell shape, reminiscent of the bottle cells
      known from vertebrates and several invertebrates. Presumptive endodermal cells
      organize into a field, the pre-endodermal plate, which undergoes invagination. In
      parallel, the endodermal cells decrease their apical cell contacts but remain
      loosely attached to each other. Hence, during early gastrulation they display an
      incomplete epithelial-mesenchymal transition (EMT). At a late stage of
      gastrulation, the cells eventually detach and fill the interior of the blastocoel
      as mesenchymal cells. This shows that gastrulation in Nematostella occurs by a
      combination of invagination and late immigration involving EMT. The comparison
      with molecular expression studies suggests that cells expressing snailA undergo
      EMT and become endodermal, whereas forkhead/brachyury expressing cells at the
      ectodermal margin of the blastopore retain their epithelial integrity throughout
      gastrulation.

PMID- 16416138
TI  - Calculation of polyamides melting point by quantum-chemical method and BP
      artificial neural networks.
AB  - Quantitative structure-property relationships (QSPR) for the melting point of the
      polyamides have been determined. All descriptors were calculated from molecular
      structures at the B3LYP/6-31G(d) level and a QSPR model was generated by multiple
      linear regression (MLR). The important molecular descriptors for polyamide
      melting-point temperatures (T (m)) are the number of benzene rings in the
      backbone chain, the proportion of methylene and acylamino in the backbone chain,
      the total molecular energy and the atomic charge for the oxygen atom in the
      acylamino group. The MLR determination coefficient (r2) and the standard error of
      estimation for the model are 0.865 and 21.34 K, respectively. In addition to the
      nonlinear regression technique, error back-propagation artificial neural networks
      (BPANN) was used to study the relationships between molecular structures and
      melting-point temperatures. It is concluded that melting-point temperatures for
      polyamides can be described by molecular chain rigidity and interchain attractive
      interactions. The more accurate predicted results were obtained from BPANN.
      Figure Experimental vs calculated Tm using BPANN. [Figure: see text].

PMID- 16416139
TI  - Density functional computations of enantioselective alkynylation of aldehyde
      catalyzed by chiral zinc(II)-complexes.
AB  - The enantioselective alkynylation of aldehyde catalyzed by chiral zinc(II)
      complexes was studied by means of the density functional theory (DFT). All the
      structures were optimized completely at the B3LYP/6-31G(d,p) level. To obtain
      more exact energies, single-point energy calculations at B3LYP/6-31+G(d,p) level
      were carried out on the B3LYP/6-31G(d,p) geometries. As shown, this
      enantioselective alkynylation was endothermic. The chirality-determining step for
      the alkynylation was the formation of the catalyst-ethanol complexes and the
      transition states for this step involved a six-membered ring. The dominant
      products predicted theoretically were of (R)-chirality, in good agreement with
      experiment. [Structure: see text].

PMID- 16416140
TI  - A target function for quaternary structural refinement from small angle
      scattering and NMR orientational restraints.
AB  - We present a novel target function based on atomic coordinates that permits
      quaternary structural refinement of multi-domain protein-protein or protein-RNA
      complexes. It requires that the high-resolution structures of the individual
      domains are known and that small angle scattering (SAS) data as well as NMR
      orientational restraints from residual dipolar couplings (RDCs) of the complex
      are available. We show that, when used in combination, the translational and
      rotational restraints contained in SAS intensities and RDCs, respectively, define
      a target potential function that permits to determine the overall topology of
      complexes made up of domains with low internal symmetry. We apply the target
      function on a modestly anisotropic model system, the Barnase/Barstar complex, and
      discuss factors that influence the structural refinement such as data errors and
      the geometrical properties of the individual domains.

PMID- 16416142
TI  - [Peyronie's disease. Conservative and surgical therapy].
AB  - Peyronie's disease is characterized by the formation of a plaque of the tunica
      albuginea that leads to a mainly dorsally directed penile curvature and penile
      shortening due to scarification. The exact ethiopathology remains unclear. The
      natural history of the disease is variable, ranging from spontaneous remissions
      to chronic, and including severe penile curvature. Therapy should be conservative
      in the early, painful, progressive phase. No conservative medical or semi
      invasive treatment modality, such as extracorporeal shock wave therapy or
      radiation therapy, is currently available for curing all of the symptoms of this
      disorder in all patients. All studies with a controlled design showed poor
      therapeutic outcomes that are frequently identical to the natural course.
      Surgical therapy should only be performed in the stable stage of the disease.
      This means that Peyronie's disease should have been present for at least 12
      months, and the patient should not have suffered from pain or the progression of
      symptoms for at least 6 months. The surgical treatment modalities comprise
      plication procedures (Essed-Schroeder, Nesbit), plaque-incisions with grafting,
      and the insertion of penile implants with simultaneous correction of the
      curvature by "penile cracking" or incisions of the plaque.

PMID- 16416143
TI  - [Loss of vision after non-ophthalmic surgery: systematic review of the literature
      on incidence, pathogenesis, treatment and prevention].
AB  - BACKGROUND AND GOAL: Postoperative loss of vision is a rare, but devastating
      complication after non-ocular surgery. It can occur partially or completely and
      may involve one or both eyes. Since its etiology has not yet been solved, the
      purpose of this review was to extract potential causes from the case collections
      reported to propose prophylactic measures. METHODS: A literature search was
      performed using the "Pubmed" database of the US National Library of Medicine.
      MeSH terms and combinations used were: blindness, postoperative complications,
      ischemic optic neuropathy, not ophthalmological surgical procedures, not
      neurosurgical procedures. Additionally, the results of the interim analysis of
      the postoperative visual loss (POVL) registry of the ASA were considered.
      RESULTS: The incidence of permanent loss of vision after non-ophthalmologic
      surgery is reported to be 0.0008%. However, it is elevated up to 0.11% after
      cardiac and 0.08% after spine surgery. Risk factors seem to be perioperative
      anemia, arterial hypotension and prone position, but also pre-existing diseases
      such as arteriosclerosis. Thus hemodynamic stabilization or correction of anemia
      may be successful in therapy. CONCLUSION: Patients with pre-existing
      arteriosclerotic disease scheduled for spine or cardiac surgery, but also for
      bilateral neck dissection should be informed preoperatively about the rare
      possibility of POVL. Postoperatively any visual changes should be immediately
      referred to an ophthalmologist and treated accordingly.

PMID- 16416144
TI  - Why does the phonological similarity effect reverse with nonwords?
AB  - The detrimental phonological similarity effect (PSE), a robust finding in serial
      recall of words, sometimes reverses with nonwords. The current study tested the
      hypothesis that nonwords benefit from phonological similarity because they are
      harder to retrieve. In two experiments serial recall and serial reconstruction of
      visually presented words and nonwords were compared. Phonological similarity is
      known to have a positive effect on item memory and a negative effect on position
      accuracy in serial recall, and the demands on item retrieval were greatly reduced
      in the latter task. PSE occurred for words in both tasks and was reversed for
      nonwords in serial recall, but not in serial reconstruction-a new finding in the
      literature. The following conclusions can be made: (1) the detrimental PSE on
      order retrieval occurs irrespective of lexicality, in accordance with prominent
      short-term memory models; and (2), the positive PSE on item retrieval is
      crucially affected by lexicality, a finding less well explained by the existing
      models.

PMID- 16416145
TI  - The market in diabetes.

PMID- 16416147
TI  - Cold defect on bone scan in a vertebral body after percutaneous vertebroplasty.
AB  - Percutaneous vertebroplasty using bone cements is increasingly being used to
      stabilize osteoporotic spinal compression fractures. Although the scintigraphic
      appearance of compression fractures has been well-described, the post
      vertebroplasty bone scan appearance has not. This case report describes a
      characteristic cold defect of a vertebral body after percutaneous vertebroplasty.

PMID- 16416146
TI  - Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005.
AB  - The incretin hormones are intestinal polypeptides that enhance postprandial
      insulin secretion. Gastric inhibitory polypeptide (GIP) was initially thought to
      regulate gastric acid secretion, whereas glucagon-like peptide-1 (GLP-1) was
      discovered as a result of a systematic search for intestinal insulinotropic
      products of proglucagon gene expression. The incretin effect is markedly impaired
      or absent in patients with type 2 diabetes because of decreased secretion of GLP
      1 and a loss of the insulinotropic effects of GIP. Metabolic control can be
      restored or greatly improved by administration of exogenous GLP-1, but this
      peptide is almost immediately degraded by dipeptidyl peptidase IV (DPP-IV), and
      therefore has little clinical value. DPP-IV-resistant analogues (incretin
      mimetics) have been identified or developed, and inhibitors of DPP-IV have also
      proved effective in protecting endogenous GLP-1 (and GIP) from degradation. Both
      principles have been tested in clinical studies. The incretin mimetics,
      administered by sc injection, have demonstrated lasting improvement in HbA(1)c in
      patients insufficiently treated with conventional oral therapy, and their use has
      been associated with steady weight loss for up to 2 years. The DPP-IV inhibitors,
      given once or twice daily by mouth, also appear to provide lasting improvement in
      HbA(1)c, but are weight-neutral. The first incretin mimetic has reached the
      market in the US, and applications for approval of the first inhibitors are
      expected to be filed early in 2006.

PMID- 16416148
TI  - Epidermal inclusion cyst of phalanx: a case report and review of the literature.
AB  - Epidermal cyst within a toe phalanx is an extremely rare condition. It is
      important to differentiate this benign lesion, which can be easily treated by
      curettage, from other benign and malignant lesions of the bone with a similar
      clinical presentation, and which may require amputation of the toe. This report
      describes one such lesion in the mid-phalanx of the fourth toe in a 48-year-old
      woman, and which was successfully identified by intra-operative frozen diagnosis
      and treated by curettage.

PMID- 16416149
TI  - Recovery of hand grip strength and hand steadiness after exhausting manual
      stretcher carriage.
AB  - Rescue activities frequently require not only substantial and sustained hand-grip
      forces but also a subtle coordination of hand and finger muscles, e.g. when
      manipulating injection syringes after manual stretcher carriage. We investigated
      the recovery kinetics of manual coordination and muscle strength after exhausting
      stretcher carriage (4.5 km/h, load at each handle bar: 25 kg). Hand steadiness
      (frequency and duration of wall contacts when holding a metal pin into a small
      bore) and parameters of hand-grip strength were determined in 15 male volunteers
      before and immediately after the stretcher carriage. Measurements were repeated
      after 0.5, 1, 4 and 24 h of recovery. Mean carrying time was 215+/-87 s (SD),
      mean transport distance amounted to 264+/-104 m. During the carriage test, forces
      at the stretcher handles oscillated in the order of +/-50 N within each gait
      cycle. Immediately after exhaustion, hand steadiness was significantly
      deteriorated (threefold increase in frequency and duration of wall contacts),
      maximum and mean hand-grip force over 15 s were reduced by almost 20%. While the
      recovery of hand steadiness was complete by minute 30 after stretcher carriage, a
      significant reduction in maximum and mean hand-grip force by 12% could still be
      observed after 24 h. The present findings demonstrate that hand steadiness
      recovers much faster than maximum hand-grip strength after exhaustive manual
      stretcher carriage (less than 30 min vs. more than 24 h). Probably, muscle damage
      induced in particular by the eccentric components during stretcher transport
      seems to affect only the generation of large forces. By contrast, the generation
      and coordination of the much lower forces required for hand-steadiness appears to
      be impaired only during the short transient of metabolic recovery.

PMID- 16416150
TI  - Diurnal normobaric moderate hypoxia raises serum erythropoietin concentration but
      does not stimulate accelerated erythrocyte production.
AB  - This study was performed to examine the effect of diurnal normobaric hypoxia on
      hematological parameters. Eleven healthy male volunteers were randomly selected
      to be in either the hypoxic group (n=6) or the control group (n=5). The hypoxic
      group was exposed to 8 h of normobaric hypoxia in hypoxic tent systems that
      elicited a target peripheral O(2) saturation of 81+/-2% on three consecutive
      days. The control group spent three consecutive 8-h days in modified tent systems
      that delivered normoxic air into the tent. Venous blood samples were collected
      before the exposure (days -5, 0), after each day of the exposure (days 1, 2, 3),
      and for 3 weeks after the exposure (days 7, 10, 13, 17, 24). Serum erythropoietin
      concentration significantly increased from 9.1+/-3.3 U.L(-1) to 30.7+/-8.6 U.L(
      1) in the hypoxic group. Although there were significant increases in hematocrit
      (4%), hemoglobin concentration (5%), red blood cell count (4%) on day 7 in the
      hypoxic group, these observations were likely due to dehydration or biological
      variation over time. There was no significant change in early erythropoietic
      markers (reticulocyte counts or serum ferritin concentration), which provided
      inconclusive evidence of accelerated erythroid differentiation and proliferation.
      The results suggest that the degree of hypoxia was sufficient to stimulate
      increased erythropoietin production and release. However, the duration of hypoxic
      exposure was insufficient to propagate the erythropoietic cascade.

PMID- 16416151
TI  - Adrenomedullin and elements of orthostatic competence after 41 h of voluntary
      submersion in water as measured in four healthy males.
AB  - Four men established a new score (Guinness Book of Records) by staying submersed
      in thermoneutral water (average diving depth 2.5 m) for 41 h without sleeping.
      The aim of this study is to measure circulating hormones together with plasma
      mass density and total protein concentration as indices of plasma volume change
      to test the hypotheses that (1) blood volume and related hormones are influenced
      by prolonged water submersion the same way as observed after short-term water
      immersion, and (2) plasma adrenomedullin levels change in an opposite fashion as
      with orthostatic stimulation. We also studied effects on cortisol and
      testosterone levels. Water submersion led to a 19% increase in plasma protein
      concentration and a 2.5 g/l rise in plasma mass density, corresponding to a
      15.6+/-1.1% plasma volume decrease (P=0.00). We therefore individually corrected
      (c) the observed post-submersion hormone values for plasma volume contraction.
      Based on this correction, we found a rise of plasma adrenomedullin from 7.9+/-0.9
      to 12.5(c)+/-2.3 pg/ml. Aldosterone rose from 123+/-14 to 186(c)+/-24 ng/ml
      (P=0.029); plasma renin activity increased in all four persons but the type I
      error was >0.05. Plasma testosterone decreased from 3.5+/-0.4 to 2.2(c)+/-0.6
      ng/ml (P=0.009) while plasma cortisol stayed unchanged. The daily salivary
      cortisol rhythm was preserved. We conclude that long-term water submersion has
      endocrine as well as plasma volume effects that are opposite to those seen after
      short-term immersion, and which increases plasma adrenomedullin. Circadian
      cortisol rhythm seems to be conserved even under extreme circumstances as those
      of this study.

PMID- 16416152
TI  - Meningeal solitary fibrous tumour in a child.
AB  - INTRODUCTION: Meningeal solitary fibrous tumour is a relatively recent
      pathological entity that has rarely been described in children. With radiological
      techniques, it cannot be distinguished from meningiomas, and the diagnosis has to
      be confirmed histologically. CASE REPORT: We discuss the possible histogenesis of
      this tumour and the need for recognizing this lesion as a separate entity. We
      report the case of a 12-year-old boy who developed a meningeal solitary fibrous
      tumour; the main clinical symptoms were progressive headaches for a long period
      and recent transient hemiparesis. CONCLUSION: This child presents an uneventful
      evolution without additional therapy 3.5 years after surgery.

PMID- 16416153
TI  - Functional mapping in pea, as an aid to the candidate gene selection and for
      investigating synteny with the model legume Medicago truncatula.
AB  - The identification of the molecular polymorphisms giving rise to phenotypic trait
      variability-both quantitative and qualitative-is a major goal of the present
      agronomic research. Various approaches such as positional cloning or transposon
      tagging, as well as the candidate gene strategy have been used to discover the
      genes underlying this variation in plants. The construction of functional maps,
      i.e. composed of genes of known function, is an important component of the
      candidate gene approach. In the present paper we report the development of 63
      single nucleotide polymorphism markers and 15 single-stranded conformation
      polymorphism markers for genes encoding enzymes mainly involved in primary
      metabolism, and their genetic mapping on a composite map using two pea
      recombinant inbred line populations. The complete genetic map covers 1,458 cM and
      comprises 363 loci, including a total of 111 gene-anchored markers: 77 gene
      anchored markers described in this study, 7 microsatellites located in gene
      sequences, 16 flowering time genes, the Tri gene, 5 morphological markers, and 5
      other genes. The mean spacing between adjacent markers is 4 cM and 90% of the
      markers are closer than 10 cM to their neighbours. We also report the genetic
      mapping of 21 of these genes in Medicago truncatula and add 41 new links between
      the pea and M. truncatula maps. We discuss the use of this new composite
      functional map for future candidate gene approaches in pea.

PMID- 16416154
TI  - Incidence of recurrent venous thromboembolism of patients after termination of
      treatment with ximelagatran.
AB  - OBJECTIVE: Recurrent thromboembolic events may occur after termination of
      anticoagulant therapy for acute venous thromboembolism (VTE) using oral direct
      thrombin inhibitor ximelagatran. METHODS: Patients with VTE recruited at the
      German study centres were followed-up for an additional 18 months, treated
      initially with 2x36 mg ximelagatran daily or with enoxaparin/warfarin over 6
      months (THRIVE Treatment study) and 2x24 mg ximelagatran daily or placebo over 18
      months (THRIVE III study). Recurrent VTE and the combined outcome events
      consisting of recurrent VTE, other thrombotic complication, major bleeding and
      mortality were analysed. RESULTS: In the THRIVE Treatment study, no patient
      suffered from a recurrent VTE, but 1 patient randomised to enoxaparin/warfarin
      experienced major bleeding. During follow-up, 4/32 and 3/32 patients initially
      randomised to ximelagatran and enoxaparin/warfarin developed recurrent VTE
      (p=0.7024). No major bleed occurred. One patient in each group died. The
      incidences of the combined outcome events were not different (p=0.9326). In the
      THRIVE III study, 0/9 versus 5/14 patients randomised to ximelagatran and placebo
      developed recurrent VTE including 1 fatal pulmonary embolism (p=0.0501). During
      follow-up, 3/9 and no patients initially randomised to ximelagatran and placebo
      developed recurrent VTE. One and 3 other outcome events occurred in patients
      initially randomised to ximelagatran or placebo. During follow-up, recurrent VTE
      (p=0.6893) and combined outcome events (p=0.3642) were not different between the
      groups. CONCLUSION: The results of the follow-up studies suggest that
      thromboembolic events may re-occur in patients with acute VTE after termination
      of treatment with both vitamin K-antagonists and ximelagatran.

PMID- 16416155
TI  - The utility of functional capacity evaluation: the opinion of physicians and
      other experts in the field of return to work and disability claims.
AB  - OBJECTIVES: This qualitative study explored how Dutch experts perceive the
      utility of functional capacity evaluation (FCE) for return to work (RTW) and
      disability claim (DC) assessment purposes. METHODS: Twenty-one RTW case managers
      and 29 DC experts were interviewed by telephone using a semi-structured interview
      schedule. RESULTS: The RTW case managers valued the utility of FCE on a scale of
      0-10. Their mean valuation was 6.5 (SD 1.5). The average valuation for DC experts
      was 4.8 (SD 2.2). Arguments in favor of FCE were (1) its ability to confirm own
      opinions and (2) the objectivity of its measurement method. Arguments against FCE
      were (1) the redundancy of the information it provides and (2) the lack of
      objectivity. Indications for FCE were musculoskeletal disorders, a positive
      patient self-perception of ability to work, and the presence of an actual job.
      Contraindications for FCE were medically unexplained disorders, a negative
      patient self-perception of ability to work, and the existence of disputes and
      legal procedures. CONCLUSIONS: The responding RTW case managers perceived FCE to
      be more useful than the responding DC experts. The question of whether the
      arguments presented for and against the utility of FCE are valid is one that
      should be addressed in a future study.

PMID- 16416156
TI  - The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is
      required for nicotine-conditioned place preference in mice.
AB  - RATIONALE: Tobacco use is implicated in approximately 440,000 deaths per year,
      making it the leading cause of preventable death in the United States. Although
      it is generally recognized that tobacco use is correlated with a variety of
      health-related complications, many smokers are unsuccessful in their efforts to
      stop smoking using current cessation therapies. OBJECTIVES: Given that nicotine
      is the addictive component of tobacco, successful smoking cessation therapies
      must address the various processes, including reward, which contribute to
      nicotine addiction. As such, determining the nicotinic receptor subtypes involved
      in nicotine reward is of utmost importance to understanding how nicotine
      addiction progresses. METHODS: Conditioned place preference (CPP) in three
      chamber conditioning boxes was performed. For antagonist studies, drug was given
      on all conditioning sessions 10 min before nicotine or saline injection and
      placement in the boxes. RESULTS: We have demonstrated that a pretreatment with
      the alpha4beta2 subunit of the nicotinic acetylcholine receptor (nAChR)
      antagonist dihydro-beta-erythroidine (2.0 mg/kg, s.c.) blocked nicotine (0.5
      mg/kg, s.c.) CPP in wild-type mice (C57BL/6 mice). In contrast, pretreatment with
      an antagonist of the alpha7 subunit of the nAChR, methyllycaconitine (MLA, 5.0 or
      10.0 mg/kg, s.c.), had no effect on this behavior. Finally, we showed that mice
      lacking the beta2 subunit of the nAChR did not exhibit nicotine CPP while alpha7
      knock-out mice did. CONCLUSION: Taken together, these data suggest that the beta2
      subunit of the nAChR is critically involved in nicotine reward as measured by
      CPP.

PMID- 16416157
TI  - Discrete-trials heroin self-administration produces sensitization to the
      reinforcing effects of cocaine in rats.
AB  - RATIONALE: The prevalence of cocaine use in opioid-dependent individuals is
      reportedly high, and the associated negative health and social consequences are
      severe and well documented. Sensitization of the reinforcing effects of cocaine
      has been demonstrated following noncontingent opioid exposure in animals;
      however, no preclinical studies have investigated the impact of opioid self
      administration on cocaine's reinforcing effects. OBJECTIVE: Experiments were
      designed to investigate whether access to heroin self-administration altered the
      subsequent reinforcing effects of cocaine. METHODS: Baseline responding for
      cocaine under a progressive ratio schedule was first established. Heroin was then
      self-administered under a 24-h discrete-trials procedure (DT5; access to heroin
      five times per hour). Subsequently, cocaine-maintained responding was reassessed.
      RESULTS: Here we demonstrate that 10 days of DT5 heroin self-administration (50
      microg/kg per infusion) resulted in an increase in cocaine's reinforcing effects
      at several doses across the cocaine dose-effect curve (0.38-3.0 mg/kg per
      infusion). These increases were relatively long lasting, exceeding the time
      course of a mild withdrawal syndrome. CONCLUSIONS: The DT5x10-day history of
      heroin self-administration resulted in an upward shift in the cocaine dose-effect
      curve, suggesting that DT5 heroin self-administration produced an increase in
      potency and sensitization of the maximal effectiveness with which cocaine
      functions as a reinforcer. The present experiments contribute to a growing amount
      of preclinical evidence suggesting an impact of opioid exposure on the
      reinforcing effects of cocaine, which may partially explain the high incidence of
      cocaine use in opioid-dependent individuals.

PMID- 16416159
TI  - Role of the cannabinoid system in the effects induced by nicotine on anxiety-like
      behaviour in mice.
AB  - RATIONALE: Acute behavioural effects and motivational responses induced by
      nicotine can be modulated by the endocannabinoid system supporting the existence
      of a physiological interaction between these two systems. OBJECTIVES: The present
      study was designed to examine the possible involvement of the cannabinoid system
      in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice.
      METHODS: Animals were only exposed once to nicotine. The acute administration of
      low (0.05) or high (0.8 mg/kg, s.c.) doses of nicotine produced opposite effects
      in the elevated plus-maze, i.e. anxiolytic- and anxiogenic-like responses,
      respectively. The effects of the pretreatment with the CB1 cannabinoid receptor
      antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, i.p.), and the cannabinoid
      agonist, delta9-tetrahydrocannabinol (delta9-THC, 0.1 mg/kg, ip), were evaluated
      on the anxiolytic- and anxiogenic-like responses induced by nicotine. RESULTS:
      Rimonabant completely abolished nicotine-induced anxiolytic-like effects and
      increased the anxiogenic-like responses of nicotine, suggesting an involvement of
      CB1 receptors in these behavioural responses. On the other hand, delta9-THC
      failed to modify nicotine anxiolytic-like responses but attenuated its anxiogenic
      like effects. In addition, the association of non-effective doses of delta9-THC
      and nicotine produced clear anxiolytic-like responses. CONCLUSIONS: These results
      demonstrate that the endogenous cannabinoid system is involved in the regulation
      of nicotine anxiety-like behaviour in mice and provide new findings to support
      the use of cannabinoid antagonists in the treatment of tobacco addiction.

PMID- 16416160
TI  - Evaluating disorders with a complex genetics basis. the future roles of meta
      analysis and systems biology.
AB  - Growing evidence suggests that complex gene and environment interactions underlie
      a number of diseases including chronic inflammatory diseases of the digestive
      system. The rapid advances in information and technology provide opportunities to
      discover the risks or etiology for a variety of disorders within individual
      patients. However, the availability of new data and new technology has
      outstripped the conceptual framework of simple disorders and challenges current
      statistical approaches. Here we address the issues surrounding study design and
      sample size for complex genetic traits, with special attention to meta-analysis
      and systems biology. We conclude that meta-analysis should play a limited role in
      evaluating studies of complex genetic diseases. Instead, systems biology-based
      approaches should be developed to integrate multiple, focused, and mechanistic
      association studies with the goal of assisting in the risk assessment of patients
      on a person-by-person basis.

PMID- 16416158
TI  - Developmental exposure to corticosterone: behavioral changes and differential
      effects on leukemia inhibitory factor (LIF) and corticotropin-releasing hormone
      (CRH) gene expression in the mouse.
AB  - RATIONALE: Cytokines are found in both the peripheral and central nervous system.
      There has been increasing interest in their potential role in some of the
      behavioral features of depressive disorders. Leukemia inhibitory factor (LIF), a
      proinflammatory cytokine, produces stimulation of adrenocorticotropic hormone
      (ACTH) secretion in response to emotional and inflammatory stress and recently
      has been linked to depressive-type behavior. Both the hypothalamic-pituitary
      adrenal axis and the immune system, including cytokine-mediated responses, appear
      to be susceptible to long-term programming during fetal and neonatal development.
      OBJECTIVE: The present study was designed to characterize the effects of
      perinatal exposure to corticostereone on behavior, hypothalamic LIF and
      corticotropin-releasing hormone (CRH) mRNA expression, and basal plasma
      corticosterone levels in adult female mice. METHODS: Corticosterone was added to
      the drinking water beginning the last week of gestation and continued until
      weaning. Behavior in the open field and forced swim tests, baseline plasma
      corticosterone levels, and hypothalamic LIF and CRH gene expression were
      evaluated in the adult offspring. RESULTS: Mice exposed to perinatal
      corticosterone showed increased immobility in the forced swim test and increased
      locomotor activity in the open field test. Although there were no differences
      between treatment groups in terms of basal plasma levels of corticosterone or
      hypothalamic CRH mRNA, LIF mRNA expression was increased in the hypothalamus.
      CONCLUSIONS: These results show that perinatal exposure to glucocorticoids can
      produce long-term behavioral changes and upregulation of central LIF mRNA
      expression.

PMID- 16416162
TI  - Clinical presentation and delayed treatment of cholangitis in older people.
AB  - Acute cholangitis is more common in older people, and increasing age is a
      determinant of morbidity and mortality, as is early biliary decompression by
      ERCP. This study aims to identify factors that may contribute to delays in the
      diagnosis and treatment of older people with acute cholangitis. Case notes of 122
      patients (45 aged < 75 years, 77 > 75 years) with a final diagnosis of acute
      cholangitis who underwent ERCP were reviewed for presenting clinical features
      (pain, jaundice, rigors, fever, falls, incontinence, confusion), liver function
      tests, blood count, and the interval from admission to diagnosis,
      ultrasonography, and ERCP. The most common symptom at presentation was abdominal
      pain (81%), followed by jaundice (55%). These symptoms were no less common in
      older patients. Charcot's triad was present in only 15.6% of young and 18.8% of
      older patients. Jaundice was not detected in 16% of significantly
      hyperbilirubinemic older patients, but only the presence of functional symptoms
      was associated with significant diagnostic delay (median, 1 day [range: 0-11] vs.
      9.5 days [3-25]; P< 0.001) and delay in performing ERCP (median: 4 days [0-24]
      vs. 16.5 days [2-29], P< 0.001). Overall mortality was 10%, and the incidence of
      septic shock was similar in both groups. Charcot's classical triad is infrequent
      in patients suffering from acute cholangitis. Given the greater difficulty
      assessing jaundice in older people and the confounding effect of falls,
      incontinence, and confusion, a routine policy of liver function tests, with
      further investigation of abnormal results in such presentations, may reduce
      delays in diagnosing and treating acute cholangitis.

PMID- 16416161
TI  - Calcitonin-secreting VIPoma.

PMID- 16416163
TI  - A gastric fistula with a pancreatic mucinous tumor.

PMID- 16416164
TI  - Primary malignant fibrous histiocytoma of the pancreas: a case with K-ras
      mutation and a review of the literature.

PMID- 16416165
TI  - A phase II trial of irinotecan in patients with previously untreated advanced
      esophageal and gastric adenocarcinoma.
AB  - Chemotherapy options for esophagogastric adenocarcinoma remain limited.
      Irinotecan has demonstrated broad activity in a variety of epithelial
      malignancies. Forty-six patients with previously untreated, measurable,
      unresectable, or metastatic esophagogastric adenocarcinoma were enrolled.
      Patients received irinotecan (125 mg/m2 intravenously over 90 min weekly) for 4
      consecutive weeks followed by a 2-week rest. Forty-three patients received at
      least one treatment and were evaluable for response and toxicity. One complete
      and five partial responses were observed, for an overall response rate of 14%
      (95% CI, 4-24%). Median survival for all 43 patients was 6.4 months (95% CI, 4.6
      8.2 months). Grade 3 to 4 toxicity included 10 patients (23%) with neutropenia,
      13 patients (30%) with late diarrhea, 6 patients (14%) with vomiting, and 6
      patients (14%) with fatigue. We conclude that although single-agent irinotecan is
      an active agent for esophagogastric adenocarcinoma, the schedule utilized in this
      trial is associated with moderate toxicity. When used as a single-agent, a tri
      weekly schedule may be preferable for this patient population.

PMID- 16416166
TI  - CD54 expression is predictive for lymphatic spread in human gastric carcinoma.
AB  - Even among gastric carcinoma cases with a similar extent of lymphatic invasion,
      the number of diseased lymph nodes may vary. Other factors might also contribute
      to the process of lymphangitic metastasis. Primary gastric tumors with the same
      extent of pathologic lymphatic invasion were studied in 78 patients. We
      investigated the correlation between CD54 expression on cancer cells and
      clinicopathologic features. Decreased CD54 expression on cancer cells was
      significantly correlated with the number of involved lymph nodes and the extent
      of lymph node spread. The number of diseased lymph nodes was associated with the
      prognosis of patients with gastric carcinoma. The CD54-negative group had a
      significantly worse prognosis than the CD54-positive group. These findings
      suggested that CD54 expression is predictive for lymphatic spread and prognosis
      in human gastric carcinoma.

PMID- 16416167
TI  - Magnitude of combination therapy of radical resection and external beam
      radiotherapy for patients with carcinomas of the extrahepatic bile duct and
      gallbladder.
AB  - The present study sought to identify the therapeutic efficacy of adjuvant
      external beam radiotherapy (EBRT) for carcinomas of the extrahepatic bile duct
      (EHBD) and gallbladder. Twenty-one patients with pathologically verified EHBD
      carcinoma and 18 patients with gallbladder carcinoma were analyzed
      retrospectively by Cox regression analysis for predictors of survival. The
      overall 5-year survival rates after resection were 33% for EHBD carcinoma and 56%
      for gallbladder carcinoma. The overall 5-year survival rate for EHBD carcinoma
      was 60% in 8 patients without microscopic residual disease (R0), 15% in 9
      patients with microscopic residual tumor (R1), and 0% in 4 patients with
      macroscopic residual tumor (R2). The overall 5-year survival rate of gallbladder
      carcinoma patients was also decreased with R status equal to 73%, 40%, and 0% for
      R0, R1 and R2, respectively. Adjuvant radiotherapy significantly improved the 5
      year survival rate in 7 patients with R1 disease of EHBD carcinoma (P = .035),
      compared with survival in 2 patients who underwent resection alone. However, no
      significant difference was noted in the 5-year survival rate between the
      resection plus EBRT group and the resection alone group for gallbladder
      carcinoma. Multivariate analysis revealed that histopathologic grade (G) was an
      independent predictor of survival for EHBD carcinoma and that direct invasion of
      liver parenchyma was a predictor of survival for gallbladder carcinoma. This
      study suggests that curative resection provides the best survival for patients
      with EHBD and gallbladder carcinoma, and that radiotherapy may play a beneficial
      role in controlling local-regional residual EHBD carcinoma tumors. However, new
      strategies for adjuvant therapy are needed to improve survival in patients with
      gallbladder carcinoma.

PMID- 16416169
TI  - Semiurgent endoscopic PEG tube replacement as a treatment for early initial PEG
      tube dislodgement in the immune-compromised patient.

PMID- 16416170
TI  - Small intestinal lipoma as a cause of massive gastrointestinal bleeding
      identified by intraoperative enteroscopy. A case report and review of the
      literature.

PMID- 16416168
TI  - Primary colon lymphoma in Korea: a KASID (Korean Association for the Study of
      Intestinal Diseases) Study.
AB  - Although almost all primary colorectal lymphomas are of B-cell lineage in Western
      countries, primary colorectal T-cell lymphomas are not uncommon in the East. The
      aim of this study was to review the clinical characteristics and treatment
      outcomes of primary colorectal lymphomas, with special emphasis on the
      differences between T-cell and B-cell lymphomas. Ninety-five cases of primary
      colorectal lymphomas that satisfied Dawson's criteria were identified from the
      clinical databases of 13 university hospitals in Korea. The mean age at the time
      of presentation was 51.1 years and the male:female ratio was 64:31. The clinical
      information, including endoscopic and histological characteristics, was
      retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%)
      were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T
      cell lymphomas presented at a younger age than patients with B-cell lymphomas
      (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom
      was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night
      fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The
      most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and
      ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas.
      Intussusception was more common in B-cell lymphomas than in T-cell lymphomas
      (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T
      cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005).
      The prognosis was significantly worse for T-cell lymphomas than for B-cell
      lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by
      multifocal ulcerative lesions in relatively young patients, a high rate of
      hematochezia, fever, or perforation, and a poor prognosis even for cases of
      localized disease.

PMID- 16416171
TI  - EUS diagnosis of an unusual case of pylephlebitis mimicking metastatic pancreatic
      cancer.

PMID- 16416172
TI  - Laparoscopic radiofrequency-assisted liver resection (LRR): a report of two
      cases.

PMID- 16416173
TI  - A possible role of GLP-1 in the pathophysiology of early dumping syndrome.
AB  - Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after
      oral glucose in gastrectomy patients, resulting in late dumping syndrome.
      Recently, we showed that GLP-1 elicits the activation of sympathetic outflow.
      Because sympathetic activation is thought to be a cause of early dumping, we
      hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of
      early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood
      pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine,
      GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In
      gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min
      after oral glucose. Significant positive correlations were found among GLP-1,
      norepinephrine, and heart rate at 30 min, and these parameters at 30 min were
      significantly higher in patients with early dumping syndrome. These results
      suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.

PMID- 16416174
TI  - The incidence of abdominal and pelvic surgery among patients with irritable bowel
      syndrome.
AB  - Rates of abdominopelvic surgery, with a particular focus on gallbladder
      procedures, were measured in patients with irritable bowel syndrome (IBS) (n =
      108,936) and compared with those in a general population sample (n = 223,082).
      The patient sample was selected from persons who were members of a managed care
      organization during the years 1995-2000. Medical records from a randomly selected
      subset of IBS patients were reviewed to confirm the diagnosis. Crude and
      standardized rates and adjusted rate ratios for surgery were calculated. The
      incidence of abdominopelvic surgery, excluding gallbladder procedures, was 87%
      higher in patients with IBS than that for the general population. The incidence
      of gallbladder surgery was threefold higher in IBS patients than the general
      population. Patients with IBS have an increased risk for abdominopelvic and
      gallbladder surgery and, thus, an associated risk for experiencing morbidity and
      mortality associated with these surgical procedures.

PMID- 16416175
TI  - Regional postprandial differences in pH within the stomach and gastroesophageal
      junction.
AB  - Our objective was to determine regional differences in intragastric pH after
      different types of meals. Ten normal subjects underwent 27-hr esophagogastric pH
      monitoring using a four-probe pH catheter. Meals were a spicy lunch, a high-fat
      dinner, and a typical bland breakfast. The fatty dinner had the highest
      postprandial buffering effect, elevating proximal and mid/distal gastric pH to
      4.9 +/- 0.4 and 4.0 +/- 0.4, respectively, significantly (P < 0.05) higher
      compared to 4.2 +/- 0.3 and 3.0 +/- 0.4 for the spicy lunch and 3.0 +/- 0.3 and
      2.5 +/- 0.8 for the breakfast. The buffering effect of the high-volume fatty meal
      to pH > 4 was also longer (150 min) compared to that of the spicy lunch (45 min)
      and the bland breakfast, which did not increase gastric pH to > 4 at any time.
      Proximal gastric acid pockets were seen between 15 and 90 min postprandially.
      These were located 3.4 +/- 0.8 cm below the proximal LES border, extending for a
      length of 2.3 +/- 0.8 cm, with a drop in mean pH from 4.7 +/- 0.4 to 1.5 +/- 0.9.
      Acid pockets were seen equally after the spicy lunch and fatty dinner but less
      frequently after the bland breakfast. We conclude that a high-volume fatty meal
      has the highest buffering effect on gastric pH compared to a spicy lunch or a
      bland breakfast. Buffering effects of meals are significantly higher in the
      proximal than in the mid/distal stomach. Despite the intragastric buffering
      effect of meals, focal areas of acidity were observed in the region of the cardia
      gastroesophageal junction during the postprandial period.

PMID- 16416176
TI  - Natural course of functional dyspepsia after Helicobacter pylori eradication: a
      seven-year survey.
AB  - The role of Helicobacter pylori(Hp) in functional dyspepsia (FD) is controversial
      and previously published data do not help to clarify whether Hp eradication
      affects the natural course of FD. The aim of this study was to assess the
      clinical course of FD during a long follow-up period of 7 years in a homogeneous
      sample of Hp-eradicated patients. Among patients referred between 1991 and 1996,
      patients with FD and infected with Hp were enrolled. Patients were administered a
      structured symptom questionnaire and evaluated after Hp eradication at each 12
      month time points. Patients were divided into three FD subgroups: predominantly
      ulcer-like, dismotility-like, and reflux-like symptom clusters. A composite
      symptom score ranging from 0 (no symptom) to 3 (severe symptoms) was assigned to
      each FD cluster. Of the 1685 screened patients, 405 had FD and 211 of them
      (52.1%) were also Hp-positive. During the follow-up, the amount of missing
      information varied from 10% to 17.5% within the first 6 years and was 30.8% at 7
      years. The rates of improved patients ranged from 33% (reflux-like) to 34.9%
      (dismotility-like) to 47.3% (ulcer-like). However, only a proportion of 10%-50%
      of them was symptom-free after eradication and also at each 12-month evaluation,
      whereas the other patients became symptomatic at different times. FD symptoms
      slightly improve after Hp eradication over a long period of time but a large
      percentage of these improved patients may experience FD symptoms again, even
      after some years of well-being after Hp eradication.

PMID- 16416178
TI  - Oral vaccination against Helicobacter pylori infection is not effective in mice
      with Fas ligand deficiency.
AB  - The aim of this study was to delineate the role of the Fas pathway in vaccination
      against Helicobacter pylori. C57BL/6 and Fas ligand-deficient (gld) mice were
      divided into 3 groups: control, H. pylori infected, and orally vaccinated (H.
      pylori whole cell sonicate and cholera toxin adjuvant). Oral vaccination
      prevented H. pylori colonization in 78% of C57BL/6 mice compared to only 18% of
      gld mice. Vaccination did not alter the degree of apoptosis in either strain of
      mice. Vaccination led to significant increase in interleukin (IL)-5 and IL-10 in
      C57BL/6 but not gld mice. H. pylori infection increased interferon (IFN)-gamma
      levels in C57BL/6 but not in gld mice while vaccination had no effect on IFN
      gamma levels in either strain. Oral vaccination is not effective in Fas ligand
      deficient mice likely owing to lack of effective cytokine responses. This
      indicates that the Fas pathway plays a critical role in promoting an appropriate
      effector response following H. pylori vaccination.

PMID- 16416177
TI  - Association of adenosine deaminase, superoxide dismutase, and catalase activities
      with Helicobacter pylori.
AB  - Our purpose was to investigate associations between adenosine deaminase (ADA),
      superoxide dismutase (SOD), and catalase (CAT) activities and H. pylori.Ninety
      nine patients were studied. Eight antral mucosal biopsies were taken for
      biochemical assessment of ADA, CAT, AND SOD activity and histological assessment.
      H. pylori density wAS evaluated according to the updated Sydney system. Patients
      were divided into three groups according to Sydney classification. ADA activity
      was found to be higher in patients having H. pylori in the present study. Also,
      ADA activity was higher in patients with a severe density of H. pylori. SOD level
      was found to be significantly higher with increased H. pylori density in our
      study (P < 0.05). In addition, SOD activity was higher in it H. Pylori-positive
      than H. pylori-negative patients. We did not find CAT activity in some antral
      tissue specimens. The significantly high levels of ADA activity in patients with
      H. pylori infection may reflect the regulator role of ADA in acid secretion. The
      higher ADA level with increased H. pylori density and H. pylori positivity
      indicate the probable malign lymphoid process of the stomach. But these findings
      must be confirmed with larger studies that include different gastric lesions.

PMID- 16416179
TI  - Inadequate use of acid-suppressive therapy in hospitalized patients and its
      implications for general practice.
AB  - Acid-suppressive therapy (AST) is largely prescribed in both hospital and general
      practice setting but few data are available on appropriateness of AST use in
      hospitalized patients and its fallout on prescribing in general practice. We
      assessed AST in patients consecutively admitted to an internal medicine
      department to determine the type and timing of prescription and indication for
      use according to widely accepted guidelines. Prescriptions were rated as
      indicated, acceptable, or not indicated. Overall, 58.7% of 834 admitted patients
      received AST, mainly proton pump inhibitors. The prescriptions were indicated in
      50.1% of patients, not indicated in 41.5%, and acceptable in 6.5%. The main
      reason for inappropriate use was prophylaxis in low-risk patients (64.8%). On
      admission, 35.7% of 112 patients already on AST were judged to receive
      inappropriate prescription; of 348 patients discharged on AST, overuse was
      identified in 38.5%. No significant difference was observed for inappropriate use
      at admission, during hospitalization, and at discharge. In 64 inpatients (7.7%)
      AST, although indicated, mainly for ulcer prophylaxis in high-risk patients, was
      not prescribed. In conclusion, AST is substantially over-used in both hospital
      and general practice settings, mainly for ulcer prophylaxis in low-risk patients.
      On the other hand, AST is underused in a small, but not negligible proportion of
      high-risk patients.

PMID- 16416180
TI  - A higher dose requirement of tacrolimus in active Crohn's disease may be related
      to a high intestinal P-glycoprotein content.
AB  - Tacrolimus, a relatively new therapeutic option for patients with corticosteroid
      refractory Crohn's disease or ulcerative colitis, is a substrate for the apically
      directed efflux transporter P-glycoprotein (P-gp). Duodenal biopsy specimens
      obtained from a patient with corticosteroid-refractory Crohn's disease and with
      significantly higher-than-average tacrolimus dose requirements were analyzed for
      P-gp by Western blot. The P-gp content in this patient was more than double that
      in specimens obtained from 9 of 10 healthy subjects. Elevated intestinal P-gp
      could have resulted in decreased tacrolimus absorption, thereby leading to
      decreased blood concentration and decreased efficacy in this patient. The cause
      and prevalence of this phenomenon are unknown.

PMID- 16416181
TI  - Gastroduodenal Crohn's disease is associated with NOD2/CARD15 gene polymorphisms,
      particularly L1007P homozygosity.
AB  - Limited data exist on the specific association between gastroduodenal Crohn's
      disease (GDCD) and NOD2/CARD15 gene polymorphisms. The aim of this study was to
      assess the association between NOD2 polymorphisms and GDCD, and to assess the
      specific association between each of the 3 major allelic variants G908R, L1007P,
      and R702W and the clinical features of Crohn's disease. We retrospectively
      reviewed the records of 202 patients with confirmed Crohn's disease and complete
      data was performed. Seventy-one patients (35%) had at least 1 allelic variant: 55
      had 1 variant, 4 were homozygous for L1007fs, 2 homozygous for R702W, and 10 were
      compound heterozygous. Eighteen patients with confirmed GDCD were identified; 10
      (56%) had wild type, 4 (22%) had 1 variant, and 4 (22%) had 2 allelic variants (2
      were L1007P homozygous and 2 compound heterozygous). Compared to patients without
      gastroduodenal involvement, those with GDCD were more likely to have 2 allelic
      variants (22% vs. 6%; odds ratio [OR] 2.7; 95% confidence interval [CI] 1.6-7.3)
      and to be homozygous for L1007P (11% vs. 1%; OR 5.2; 95% CI 2.5-9.4). G908R
      heterozygosity was associated with ileal involvement (OR 1.4; 95% CI 1.1-2.9) and
      smoking habits (OR 2.4; 95% CI 1.2-3.8), whereas L1007P homozygosity was
      associated with GDCD (OR 5.8; 95% CI 2.6-10.8). L1007P variation was associated
      with younger age at diagnosis as well. There was no specific association between
      R702W homo- or heterozygosity and any of the characteristics examined. In
      conclusion, GDCD is associated with double dose of the NOD2/CARD15 gene variants,
      particularly L1007P homozygosity. There is evidence of specific variant-phenotype
      associations. G908R heterozygosity is associated with ileal involvement and
      smoking, whereas L1007P homozygosity is strongly associated with GDCD and younger
      age at diagnosis.

PMID- 16416182
TI  - Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis:
      a prospective study report.
AB  - Rebamipide has a broad spectrum of pharmacological actions that include
      suppression of neutrophil functions and stimulation of mucosal epithelial cell
      regeneration by increasing the expression of epithelial growth factor (EGF) and
      the EGF receptor. Sixteen patients with active ulcerative colitis (UC; mild in 1
      patient, moderate in 11, and severe in 4) were recruited. Enemas containing 150
      mg rebamipide per dosing were administered during the daytime after passage of
      stool, twice a day for 4 weeks. UC disease activity index (UC-DAI), endoscopic
      activity index (EAI), and Floren's grading (FG) of mucosal biopsy specimens were
      measured at entry and at 4 weeks. Five of 16 patients did not complete the study,
      and therefore, final efficacy assessment was done on 11 patients who completed
      the 4 weeks of treatment. Improvements were observed in UC-DAI (P = 0.0049), EAI
      (P = 0.0043), and FG (P = 0.0084). There was no serious rebamipide-related side
      effect in any of the 16 patients. In conclusion, rebamipide topical therapy
      appears to be effective for the treatment of mildly to moderately active distal
      UC. Further controlled studies are warranted for this promising drug.

PMID- 16416183
TI  - Pancreatic autoantibodies in Greek patients with inflammatory bowel disease.
AB  - Pancreatic autoantibodies (PAbs) have been suggested as a specific but not
      sensitive marker for Crohn's disease (CD). The aim of this study was to assess
      the value of detecting PAbs in Greek patients with ulcerative colitis (UC) and
      CD. Sera were collected from 150 patients with IBD (73 with UC and 77 with CD),
      31 cases with non-IBD intestinal inflammation, 16 cases with other autoimmune
      diseases, and 104 healthy controls. Determination of PAbs was performed by a
      standard indirect immunofluorescence technique. PAbs were detected in 18 of 73
      (24.7%) samples from UC patients and in 32 of 77 (41.6%) samples from CD
      patients. The prevalence of positive PAbs was significantly higher in CD than in
      UC (P = 0.04). None of the 104 samples from healthy controls and the 31 cases
      with non-IBD intestinal inflammation had detectable PAbs. One patient with
      Sjogren's syndrome was PAbs positive. No association of PAbs with IBD activity,
      IBD localization, or medical treatment was found. Patients with stenotic CD had a
      significantly higher prevalence of PAbs positivity (60%) compared with patients
      with inflammatory (28.6%) and fistulizing (41.2%) disease (P = 0.02). The
      prevalence of PAbs in Greek CD patients was found to be similar to that in
      previous reports. In contrast to these studies we found also increased prevalence
      of PAbs in UC patients. These findings suggest that PAbs should be considered as
      a specific marker for IBD rather than for CD.

PMID- 16416184
TI  - Development of primary biliary cirrhosis in a patient with Crohn's disease: a
      case report and review of the literature.

PMID- 16416185
TI  - Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a term often used to describe two
      related conditions: a relatively benign, nonalcoholic fatty liver (NAFL) and
      potentially aggressive, nonalcoholic steatohepatitis (NASH). Both conditions
      (NAFL and NASH) occur in the setting of peripheral insulin resistance. Recently,
      obstructive sleep apnea (OSA) has been proposed as an independent risk factor for
      insulin resistance. To date, few studies have documented the prevalence of OSA or
      symptoms of OSA (SOSA) in NAFLD patients. The objectives of this study were (1)
      to document the prevalence of SOSA in patients with NAFLD and (2) to determine
      whether prevalence rates for SOSA differ in NAFL versus NASH patients. One
      hundred ninety biochemically defined NAFLD patients (116 NAFL and 74 NASH), of
      whom 50 (18 NAFL and 32 NASH) had undergone liver biopsy, completed a Modified
      Berlin Sleep Apnea Questionnaire for SOSA. Risk factors for NAFLD were also
      documented in NAFL and NASH patients. Eighty-seven of the 190 (46%) NAFLD
      patients met questionnaire criteria for SOSA. The prevalence of SOSA was similar
      in both biochemically (45% versus 49%, respectively; P = 0.66) and histologically
      (39% versus 63%, respectively; P = 0.11) defined NAFL and NASH patients. Other
      risk factors for NAFLD such as body mass index, plasma cholesterol and
      triglyceride levels, and prevalence of diabetes were also similar in the two
      groups. Approximately one-half of NAFLD patients, whether NAFL or NASH, have
      SOSA. Further studies are required to determine whether a causal link exists
      between NAFLD and OSA.

PMID- 16416186
TI  - Effects of combined antiviral therapy on asymptomatic mixed cryoglobulinemia in
      naive patients with chronic hepatitis C virus infection: a preliminary study.
AB  - The clinical spectrum of mixed cryoglobulinemia embraces several manifestations:
      recurrent vascular purpura, weakness, arthralgia/arthritis, glomerulonephritis,
      peripheral neuropathies, and Raynaud's phenomenon. Mixed cryoglobulinemia is
      currently treated with steroids, low-antigen content diet, immunosuppressors,
      plasma exchange, and antiviral therapy, namely, alpha -interferon alone or, more
      recently, in association with ribavirin. In the present research, we verified the
      effectiveness of combined therapy with interferon and ribavirin on asymptomatic
      mixed cryoglobulinemia in naive (never treated before) patients with chronic
      hepatitis C. We enrolled 50 consecutive patients, 31 males and 19 females, with
      chronic hepatitis C who showed a sustained response to combined antiviral therapy
      (interferon and ribavirin). Before treatment, cryoglobulins were detected in 25
      subjects (50%). Only 1 of the 25 patients with asymptomatic mixed
      cryoglobulinemia had persistence of cryoglobulins at the end of the follow-up
      period. Unexpectedly, in 7 of 25 subjects without mixed cryoglobulinemia before
      treatment, cryoglobulins became detectable after antiviral therapy. Our present
      study first reports the onset of asymptomatic mixed cryoglobulinemia in hepatitis
      C virus patients after clearance of the virus from blood obtained with a combined
      antiviral treatment. Possible explanations are discussed. Our data also suggest
      that the appearance of a clinically evident mixed cryoglobulinemia cannot be
      excluded in this kind of subject.

PMID- 16416187
TI  - Hepatitis C virus genotype 5 in southern belgium: epidemiological characteristics
      and response to therapy.
AB  - Data are scarce on patients infected with hepatitis C virus of genotype 5, due to
      the low prevalence of this genotype around the world. To better define the
      characteristics of these patients, we reviewed the files of 16 genotype 5
      patients. Mean age was 38 +/- 14. All patients were of European origin. Most of
      them (75%) had been contaminated by transfusion within a short time period
      (between 1980 and 1991). There were no intravenous drug addicts. Seven patients
      received treatment. One patient did not respond to interferon (IFN) monotherapy.
      Of four patients treated with IFN and ribavirin, three became sustained viral
      responders. Two patients treated with pegylated IFN and ribavirin became
      sustained viral responders. In our region, genotype 5 patients seem to have been
      contaminated within a relatively short time period. Treatment with IFN or
      pegylated IFN and ribavirin gave a high rate (83%) of sustained viral responses.

PMID- 16416188
TI  - Hepatitis C virus risk factors in the Turkish community.
AB  - Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the
      worldwide. This infection is often insidious and one-half of infected patients
      are asymptomatic. Determination of risk factors for HCV transmission is very
      important. The aim of this study was to assess the risk factors, transmission to
      spouses and children for HCV infection in Turkish population. One hundred and
      fifty-one patients with chronic hepatitis C and 151 control cases were
      investigated for the probable risk factors of HCV infection. Complete blood
      count, ALT, AST, albumin, prothrombin time, upper abdomen ultrasonography
      assessment and percutaneous liver biopsy (not for cirrhotics) were performed in
      all patients with chronic hepatitis C. Anti-HCV testing was done by using second
      generation ELISA in 302 cases. Minor surgical operation (p < 0.001), major
      surgical operation (p = 0.001), blood transfusion (p < 0.001), multi-partner sex
      (p < 0.05), frequent dental therapy (p < 0.05), and dental extraction (p < 0.001)
      in patients with a chronic HCV infection were found to be higher than the control
      group. No significant difference was found in other risk factors. The rate of
      hepatitis C virus in index cases was found to be 1.8% in their spouses and 1.2%
      in their children. Our study showed that surgical operation, frequent dental
      therapy, dental extraction, multi-partner sex, and blood transmission are the
      main risk factors for HCV infection in Turkish community.

PMID- 16416189
TI  - Emergent stent occlusion for TIPS-induced liver failure.

PMID- 16416190
TI  - Intestinal B cell lymphoma associated with chronic hepatitis C and celiac
      disease.

PMID- 16416191
TI  - Portal vein thrombosis due to hyperhomocysteinemia caused by vitamin B-12
      deficiency.

PMID- 16416192
TI  - Acute icteric hepatitis induced by a short course of low-dose cyclophosphamide in
      a patient with lupus nephritis.

PMID- 16416193
TI  - NF-kappaB activation precedes increases in mRNA encoding neurokinin-1 receptor,
      proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium
      induced colitis in rats.
AB  - Nuclear factor kappa B (NF-kappa B) plays a key role in initiating inflammation
      associated with colitis. A systematic study was conducted in the rat DSS colitis
      model to determine the temporal relationship between NF-kappa B activation and
      expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory
      cytokines, and adhesion molecules. Rats were given 5% DSS in their water and
      sacrificed daily for 6 days. Colon tissue was collected for assessment of
      histological changes, NF-kappa B activation, myeloperoxidase (MPO) activity, and
      expression of NK-1R, SP, TNFalpha, IL-1beta, VCAM-1, ICAM-1, E-selectin, CINC-1,
      MIP-1alpha, and iNOS. NF-kappa B activation increased, biphasically, on Day 1 and
      again on Days 4-6. The mRNA levels for ICAM-1, CINC-1, IL-1beta, TNFalpha, VCAM
      1, and NK-1R rose significantly (P < 0.05) by 2-4 days. Increased iNOS mRNA
      levels, MPO activity, and mucosal damage occurred on Day 6. These data
      demonstrate that NF-kappa B activation substantially precedes the onset of
      physical disease signs and active inflammation.

PMID- 16416194
TI  - Oral insulin enhances intestinal regrowth following massive small bowel resection
      in rat.
AB  - Experimental studies have suggested that insulin (INS) plays an important role in
      small intestinal growth and development. In the present study we investigated the
      effect of oral INS on structural intestinal adaptation and enterocyte
      proliferation and loss via apoptosis in a rat model of short bowel syndrome
      (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham
      rats underwent bowel transection, SBS rats underwent 75% small bowel resection,
      and SBS-INS rats underwent bowel resection and were treated with oral INS given
      in the drinking water from the 3rd to the 15th postoperative day. Parameters of
      intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villous
      height, and crypt depth), enterocyte proliferation, and apoptosis were determined
      on day 15. SBS-INS rats demonstrated a significant increase (vs SBS rats) in
      jejunal and ileal overall bowel and mucosal weight, ileal mucosal DNA and
      protein, ileal villous height, and crypt depth. SBS-INS rats also showed an
      increased cell proliferation index in jejunum and ileum and decreased apoptotic
      index in jejunum compared to SBS animals. In conclusion, in a rat model of SBS,
      oral INS strongly enhances intestinal adaptation. Possible mechanisms may include
      increased cell proliferation and decreased enterocyte loss via apoptosis.

PMID- 16416195
TI  - Essential fatty acid deficiency in a severely malnourished patient receiving
      parenteral nutrition.

PMID- 16416196
TI  - Two cases of eosinophilic gastroenteritis and malabsorption due to Enterobious
      vermicularis.

PMID- 16416200
TI  - Pancreaticopleural fistula: report of two cases and review of the literature.
AB  - Pancreaticopleural fistulas are a rare complication of pancreatitis. We report
      two cases from our institution and review 37 cases of pancreaticopleural fistulas
      identified in the literature. Endoscopic retrograde cholangiopancreatography was
      more sensitive compared to computed tomography in demonstrating
      pancreaticopleural fistulas (79% versus 43%, respectively). Medical therapy with
      total parenteral nutrition, octreotide, and/or chest tube placement was
      successful in resolving the pancreaticopleural fistula in up to 33% of cases.
      None of the patients who underwent pancreatic duct stent and/or nasopancreatic
      drain placement required surgical intervention. Endoscopic retrograde
      cholangiopancreatography is the initial test of choice when the diagnosis of
      pancreaticopleural fistula is suspected. Early endoscopic intervention with
      pancreatic duct stent placement is recommended given its high success rate in
      fistula closure. Medical therapies are useful adjuncts to endoscopic therapy, but
      rarely result in pancreaticopleural fistula closure alone. Surgical interventions
      should only be considered after failure of endoscopic and medical therapies.

PMID- 16416202
TI  - Anticoagulation therapy may reverse biliary abnormalities due to acute portal
      thrombosis.

PMID- 16416201
TI  - Clinical significance of pulmonary function tests in patients with acute
      pancreatitis.
AB  - The aim of the present study was to investigate changes in pulmonary function
      tests (PFTs) in patients with acute pancreatitis (AP), to compare them with those
      changes in healthy controls, and to analyze the relationship between these
      parameters and computed tomography severity index (CTSI) and Ranson's criteria
      scores as markers of disease severity. This study included 40 patients with AP
      without a diagnosis of any pulmonary disease and 40 sex- and age-matched healthy
      controls. All participants were evaluated with simple PFTs and single-breath
      carbon monoxide (CO) diffusion tests. Patients with AP were also evaluated
      according to their CTSI and Ranson's criteria scores as markers of disease
      severity. The forced vital capacity (FVC), forced expiratory volume in the first
      second (FEV(1)), FEV(1)/FVC, and peak expiratory flow, which determine lung
      capacity, were similar in the two groups. The forced expiratory volume during the
      middle half of the FVC (FEF(25 - 75%)), CO diffusing capacity (D(LCO)), and ratio
      of D(LCO) to alveolar ventilation (D(LCO)/V(A)), which determines alveolar
      membrane permeability, revealed a statistically significant decline in pulmonary
      gas exchange in patients with AP (P < 0.05). Correlation analysis showed that
      there is a significant negative relationship between CTSI and Ranson's criteria
      scores with FEF(25 - 75%), D(LCO), and D(LCO)/V(A) (P < 0.05). We suggest that AP
      may cause impaired alveolar gas exchange without manifest pulmonary diseases. The
      effect of AP on FEF(25 - 75%), D(LCO), and D(LCO)/V(A) appears to be dependent
      not only on the disease, but also on its severity. FEF(25 - 75%), D(LCO), and
      D(LCO)/V(A) may give additional prognostic information in patients with AP in the
      initial evaluation.

PMID- 16416203
TI  - Biliocutaneous fistula following alveolar hydatid disease surgery treated
      successfully with percutaneous cyanoacrylate.

PMID- 16416204
TI  - Nonalcoholic fatty liver disease treated by gastroplasty.
AB  - Nonalcoholic steatohepatitis (NASH), which is the most severe histologic form of
      nonalcoholic fatty liver disease (NAFLD), is emerging as the most common
      clinically important form of liver disease in obese patients. The prevalence of
      NASH may increase with the rise in the rate of obesity and metabolic syndrome in
      affluent communities. The aim of this work is to describe clinical and
      histopathologic findings and correlate liver tissue damage to the length of
      duration of the obesity in the group of patients who underwent surgery as obesity
      treatment. Eighty-seven severely or morbidly obese patients underwent
      gastroplasty. Each patient was evaluated with complete clinical and laboratory
      medical assessment together with wedge liver biopsy taken from 59 unselected
      patients during the surgery. Patients were followed up for 41 months. Repeat
      liver biopsy was taken from 10 patients. Pathologic analysis recorded the
      presence and degree of steatosis, portal and lobular inflammation and fibrosis.
      Age, body mass index (BMI), and laboratory assessment correlated with pathologic
      data. Male patients showed more pronounced metabolic syndrome and fatty liver
      damage. Patients who become obese in childhood or as teenagers showed no
      differences in metabolic syndrome and NAFLD in mature age. There was
      statistically significant association between BMA, elevated transaminases, NAFLD,
      and fibrosis. Significant weight reduction was observed within first year after
      surgery, was slower in the second year, and stabilized within third year.
      Remarkable improvement followed in biological markers of metabolic syndrome.
      Ninety-six percent of initial liver biopsies had steatosis; 16% developed
      steatohepatitis and mild perivenular fibrosis. Significant improvement of the
      degenerative and inflammatory hepatic lesions in repeated biopsies and liver
      function readings was noted within 8 months after surgery. Obesity is a major and
      independent risk factor for the metabolic syndrome, NAFLD, NASH, and fibrosis.
      Surgical treatment improves metabolic abnormalities and hepatic lesions in long
      term observations.

PMID- 16416205
TI  - Effects of esophageal varice eradication on portal hypertensive gastropathy and
      fundal varices: a retrospective and comparative study.
AB  - Esophageal varice eradication results in gastric hemodynamic changes. The aim of
      this study was to detect the influence of variceal eradication on portal
      hypertensive gastropathy (PHG) and fundal varices and to compare the results of
      two therapeutic methods (endoscopic variceal ligation and endoscopic
      sclerotherapy). A total of 114 consecutive patients with cirrhosis and portal
      hypertension who underwent elective endoscopic variceal ligation (EVL) (85
      patients) or endoscopic sclerotherapy (EST) (29 patients) for obliteration of
      esophageal varices were selected for this study. Both groups were compared for
      PHG and fundal varice formation before and after eradication. Fifty-eight (68.2%)
      patients in the EVL and 18 (62.1%) patients in the EST group had PHG before
      esophageal varice eradication (P > 0.05). PHG grade after eradication of
      esophageal varices by both EVL and EST was significantly higher compared to pre
      eradication. PHG grade and aggregation were similar in both groups. Thirty-seven
      patients (34 F(1), 3 F(2)) in the EVL group and 13 patients (10 F(1), 3 F(2)) in
      the EST group had fundal varices before variceal eradication (P > 0.05). Fundal
      varices were detected in 46 (35 F(1), 11F(2)) and 19 (11F(1), 8F(2)) patients in
      the EVL and EST groups after eradication, respectively. There was a statistically
      significant increment in occurrence of fundal varices after eradication with EVL
      and EST groups. There was no significant difference regarding fundal varice
      development after esophageal variceal eradication in both groups. After varical
      eradication, PHG was found in 57 (87.7%) and 39 (79.6%) patients with and without
      fundal varices, respectively (P > 0.05). Esophageal eradication with EVL and EST
      increases both the incidence and the severity of PHG and fundal varice formation.
      Both methods have comparable influences on PHG and fundal varices.

PMID- 16416206
TI  - Achalasia in a patient with gastroesophageal varices: problematic treatment
      decisions.
AB  - The coexistence of achalasia and gastroesophageal varices has been reported
      sporadically in the English medical literature. We report the case of a 60-year
      old Hispanic woman with cryptogenic cirrhosis who was referred for a liver
      transplant evaluation and subsequently developed progressive dysphagia to both
      solids and liquids as well as substernal chest pain and weight loss. Endoscopy
      revealed the presence of grade I esophageal varices and large fundic varices, as
      well as retained liquid and solid food in the distal esophagus. Radiographic and
      manometric studies were consistent with achalasia. After botulinum toxin (Botox)
      injections were no longer effective a transjugular intrahepatic portosystemic
      shunt was performed for portal decompression before proceeding with pneumatic
      dilation. Optimal treatment of these 2 conditions, when they occur
      simultaneously, is problematic. We discuss this patient's management and our
      approach to this infrequent combination of diseases.

PMID- 16416208
TI  - Hepatic involvement in a patient with giant cell arteritis.

PMID- 16416209
TI  - Risk factors and ultrasound can predict chronic hepatitis caused by nonalcoholic
      fatty liver disease.
AB  - The diagnosis of nonalcoholic fatty liver disease (NAFLD) is under-recognized.
      The aim of this study was to develop a scoring system that separates NAFLD
      diagnosis as a cause of chronic hepatitis from controls by using clinical
      features and liver ultrasound. A retrospective review of consecutive NAFLD cases
      and other liver disease controls was undertaken selecting patients from an
      abnormal liver function test code. To qualify for analysis all patients had to
      have elevated liver injury tests for more then 6 months, a biopsy-confirmed
      diagnosis, and an ultrasound as part of the evaluation. There were 84 cases of
      NAFLD and 75 liver disease controls. The NAFLD group had a larger body mass index
      (BMI) (34.9 versus 26.1; P < or = 0.0001), a larger liver span (9.8 versus 8.1
      cm; P < or = 0.0001), and higher triglycerides (252 versus 142.6; P < or =
      0.0001). The ultrasound reports recorded features consistent with fatty
      infiltration in 65.5% of NAFLD cases, compared to 5.3% of other liver diseases (P
      < or = 0.0001). Diabetes mellitus was found in 35% of NAFLD and 6.7% of other
      cases (P < or = 0.0001). The BMI was >30 in 79.8% of NAFLD cases and 22.7% of
      other liver disease cases (P < or = 0.0001). The liver span was >8 cm in 78.6% of
      NAFLD cases and in only 16% of controls (P = 0.0001). On multivariate analysis
      using logistic regression, the odds ratio of having ultrasound report findings
      suggestive of fatty infiltration was 15.9 (CI, 4.1-60). The odds ratio was 9.4
      (CI, 2.3-37.9) for diabetes, 5.0 (CI, 1.7-14.6) for BMI >30, and 2.3 for liver
      span >8 cm (CI, 1.36-3.90). A scoring system using clinical features and
      ultrasound was shown to reliably separate NAFLD from other cases of chronic
      hepatitis.

PMID- 16416207
TI  - A new mutation of Wilson's disease P-type ATPase gene in a patient with cirrhosis
      and coombs-positive hemolytic anemia.

PMID- 16416210
TI  - Occurrence of autoimmune hepatitis during the course of primary biliary
      cirrhosis: report of two cases.

PMID- 16416211
TI  - Fulminant hepatic failure bridged to liver transplantation with a molecular
      adsorbent recirculating system: a single-center experience.
AB  - We herein describe the clinical course of a consecutive series of fulminant
      hepatic failure patients treated with a molecular adsorbent recirculating system
      (MARS), a cell-free albumin dialysis technique. From November 2000 to September
      2002, seven adult patients ages 22-61 (median, 41), one male (14.2%) and six
      females (85.7%), affected by fulminant hepatic failure underwent seven courses
      (one to five sessions each, 6 hr in duration) of extracorporeal support using the
      MARS technique. Pre- and posttreatment blood glucose, liver function tests,
      ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood
      gases, liver histology, Glasgow Coma Scale, and coagulation studies were
      reviewed. No adverse side effects such as generalized bleeding on noncardiogenic
      pulmonary edema, often seen during MARS treatment, occurred in the patients
      included in this study. Six patients (85.7%) are currently alive and well, and
      one (14.2%) died. Four patients (57%) were successfully bridged (two patients in
      1 day and two other patients in 4 days) to liver transplantation, while two (5%)
      recovered fully without transplantation. All the measured variables stabilized
      after commencement of the MARS. No differences were noted between the pre- and
      the post-MARS histology. We conclude that the MARS is a safe, temporary life
      support mechanism for patients awaiting liver transplantation or recovering from
      fulminant hepatic failure.

PMID- 16416214
TI  - Desmoid tumor presenting as intra-abdominal abscess.

PMID- 16416212
TI  - Opposite association of serum prolactin and survival in patients with colon and
      rectal carcinomas: influence of preoperative radiotherapy.
AB  - Prolactin (PRL) is a pleiotropic hormone associated with the progression of
      various cancers, including colorectal cancer (CRC). Here we investigate whether
      the association of serum PRL concentration and survival is affected by tumor
      location and preoperative radiotherapy (PRERT) in patients with CRC cancer. Serum
      PRL was determined in 82 CRC patients without previous treatment. Patients with
      PRL concentrations at and above the 75th percentile (high PRL) or below this
      level (low PRL), had a significant correlation with overall survival determined
      using the Kaplan-Meier method. In colon cancer, there was an increased risk of
      mortality when PRL values were at and above the highest quartile (22% vs. 73%; P
      = 0.01). In contrast, in rectal cancer, high PRL values were associated with a
      significant overall survival advantage (88% vs. 44%; P = 0.05), which became more
      significant (100% vs. 34%; P = 0.005) when only rectal cancer patients receiving
      PRERT were compared. These findings suggest that tumor location and adjuvant
      radiotherapy influence the association between circulating PRL and survival in
      CRC.

PMID- 16416213
TI  - Acute liver failure as an initial manifestation of an infiltrative hematolymphoid
      malignancy.

PMID- 16416215
TI  - Coexistence of splenic non-Hodgkin's lymphoma with hepatocellular carcinoma in a
      patient with chronic hepatitis C.

PMID- 16416216
TI  - Primary esophageal lymphoma: case series and review of the literature.

PMID- 16416217
TI  - Validation of the blood quininium resin test for assessing gastric
      hypochlorhydria.
AB  - Although gastric hypochlorhydria is a risk factor for gastroenteritis and for
      gastric cancer, no reliable, inexpensive, noninvasive test exists for screening
      or epidemiologic studies. We aimed to evaluate the sensitivity and specificity of
      the blood quininium resin test (bQRT) for hypochlorhydria, against pH monitoring.
      Twelve fasting adult volunteers-seven with and five without H. pylori infection
      ingested 80 mg/kg of quininium resin twice, once with and once without acid
      suppression. Gastric pH was monitored for 75 minutes; serum samples were obtained
      at times 0 and 75 minutes. The bQRT levels were compared to gastric pH,
      controlling for omeprazole use and H. pylori infection. Subjects with a median
      recorded pH > or =3.5 were considered hypochlorhydric. Using a bQRT level of 10
      as a cutoff for hypochlorhydria, the sensitivity and specificity of the bQRT were
      100% and 37.5%, respectively. The bQRT predicted omeprazole use more accurately
      than pH monitoring. In conclusions, The bQRT has a high sensitivity for
      hypochlorhydria, making it potentially useful in populations with a high
      prevalence of hypochlorhydria. In its current formulation, the bQRT's low
      specificity makes it less useful in low-risk population.

PMID- 16416218
TI  - Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in
      a population with a high prevalence of infection: results of a 12-month
      randomized, double blind, placebo-controlled study.
AB  - Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were
      randomized to receive either lansoprazole, amoxicillin, and clarithromycin or
      lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms
      at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed
      at baseline and at 3 and 12 months. There was an overall trend, although not
      statistically significant, for a benefit of H. pylori eradication. Of the
      patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement,
      versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis,
      it was found that of the patients without endoscopic gastric erosions, 15 of 34
      (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic
      improvement (P = 0.015). Helicobacter pylori eradication did not prove to be
      clinically beneficial, although a tendency to symptomatic benefit was detected.
      Further studies are necessary to confirm the implications of endoscopic gastric
      erosions in these patients.

PMID- 16416220
TI  - Muscle shortening along the normal esophagus during swallowing.
AB  - Longitudinal shortening of the esophagus during peristaltic contraction has been
      previously analyzed globally using spaced mucosal clips. This method gives a
      relatively crude measurement. In this study, local longitudinal shortening (LLS)
      was evaluated using simultaneous high-resolution endoluminal ultrasound (HREUS)
      and manometry based on basic principles of muscle mechanics. We sought to
      determine if there are regional differences in LLS of the esophageal muscle
      during swallow-induced peristaltic contraction and evaluate shortening of the
      circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the
      esophagus. Twenty normal subjects underwent simultaneous HREUS/manometry at 4
      levels (5, 10, 15, and 20 cm above the upper border of the lower esophageal
      sphincter [LES] high-pressure zone) in the esophagus with 5-mL swallows of water.
      Ultrasound images were recorded with synchronized manometric pressure data. The
      images were digitized and the cross-sectional surface area (CSA) of the LSM, CSM,
      and total muscle (TM) were measured at baseline (at rest) and at peak
      intraluminal pressure (implying peak CSM contraction) during swallowing. LLS was
      calculated for the CSM and LSM using the principle of mass conservation, whereby
      the change in CSA relative to the resting CSA is quantitatively equal to the
      relative change in length of a local longitudinal muscle segment.CSM, LSM, and TM
      all shortened longitudinally, with the circular muscle shortening more than the
      longitudinal muscle, LLS of the CSM and TM layers at 5 cm above the LES was
      significantly greater than at 20 cm (CSM: 30% difference, P < .001; TM: 18%
      difference, P < .05). The greater shortening of LSM at 5 versus 20 cm was found
      not to be statistically significant (11% difference, P > .05). Peak intraluminal
      pressure strongly correlated with peak muscle thickness of all layers at all
      levels (r = 0.96-0.98).LLS increases from the proximal to the distal esophagus
      during bolus transport. CSM and LSM both shorten longitudinally, with CSM
      shortening more than LSM. The increase in LLS increases the efficiency of
      peristaltic contraction and likely contributes to the axial displacement of the
      LES preceding hiatal opening and esophageal emptying.

PMID- 16416221
TI  - TP53 gene mutations are rare in nondysplastic Barrett's esophagus.
AB  - In search of potential prognostic markers, we analyzed a large series of tissues
      of Barrett's esophagus and samples of adenocarcinomas arising in the terrain of
      Barrett's esophagus for TP53 gene mutations by direct sequencing of exons 5 to 9
      of the TP53 gene. While 9 of 21 adenocarcinomas tested (42.9%) contained a TP53
      mutation, none of 24 samples from Barrett's esophagus were mutated. This
      observation suggests that TP53 gene mutation may be a relatively late event in
      the progression from nondysplastic Barrett's esophagus to adenocarcinoma of
      esophagus. Therefore, TP53 gene mutations alone are not likely to represent a
      widely useful prognostic marker of the risk of progression to malignancy, at
      least not in Barrett's esophagus without dysplasia.

PMID- 16416219
TI  - Association between gastric atrophy and Helicobacter pylori infection in Japanese
      children: a retrospective multicenter study.
AB  - The purpose of this study was to determine whether Helicobacter pylori infection
      and mucosal inflammation result in gastric atrophy in Japanese children. A total
      of 196 patients ages 1-16 years were retrospectively studied: 131 patients were
      infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and
      corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney
      system. In both the antrum and corpus, H. pylori-infected patients showed
      significantly higher degrees of inflammation and activity of gastritis, compared
      with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum
      was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P <
      .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of
      intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and
      0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the
      antrum showed significantly higher degrees of H. pylori density, inflammation and
      activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was
      significantly correlated with activity, whereas in the corpus, atrophy correlated
      with H. pylori density, inflammation, and activity. H. pylori-induced gastric
      inflammation can cause atrophy in Japanese children, predominantly in the antrum.
      It remains to be determined whether H. pylori-infected children with gastric
      atrophy are at increased risk for gastric cancer.

PMID- 16416222
TI  - Lafutidine, a newly developed antiulcer drug, elevates postprandial intragastric
      pH and increases plasma calcitonin gene-related peptide and somatostatin
      concentrations in humans: comparisons with famotidine.
AB  - Lafutidine, a newly developed histamine H(2)-receptor antagonist, inhibits
      daytime (i.e., postprandial) as well as nighttime gastric acid secretion in
      clinical studies. It also has gastroprotective activity that particularly affects
      mucosal blood flow in rats. This study focused on the efficacy of lafutidine on
      plasma concentrations of gastrointestinal peptides in humans. Six healthy male
      volunteers aged 23-32 years without Helicobacter pylori infection were orally
      administered either 10 mg lafutidine, 20 mg famotidine, or water only (control)
      30 min after a standard meal (650 kcal). Plasma concentrations of lafutidine and
      famotidine were highest from 90 to 150 min after administration. Intragastric pH
      was elevated after both lafutidine and famotidine compared with the control.
      Plasma concentrations of calcitonin gene-related peptide (CGRP) and somatostatin
      were significantly increased after lafutidine at 60 and 90 min. We concluded that
      lafutidine increases plasma concentrations of CGRP and somatostatin in humans,
      which may result in inhibition of postprandial acid secretion and
      gastroprotective activity.

PMID- 16416223
TI  - Reversible edema in a male patient taking parenteral pantoprazole infusion for
      pyloric stenosis.

PMID- 16416224
TI  - Inhibition of pentagastrin-stimulated gastric acid secretion by pantoprazole and
      omeprazole in healthy adults.
AB  - Our objective was to compare the onset and duration of a single dose of
      pantoprazole or omeprazole on maximally stimulated gastric acid secretion. This
      double-blind, randomized, placebo-controlled study involved 36 healthy adults and
      utilized continuous pentagastrin infusion to stimulate acid secretion after
      administration of pantoprazole, 40 mg, omeprazole, 20 mg, or placebo. Gastric
      aspirates were collected over 24 hr and analyzed for volume, pH, and hydrogen ion
      concentration, and gastric acid outputs (GAO) were calculated. Comparison between
      GAO and intragastric pH was performed. Pantoprazole resulted in significantly
      greater inhibition of GAO than omeprazole. Mean cumulative 24-hr GAO was 164 +/-
      130 mEq for pantoprazole versus 283 +/- 159 mEq for omeprazole (P = 0.031).
      Pantoprazole patients reached and maintained GAO levels below the 10-mEq/hr
      threshold at 5.7 hr, whereas omeprazole patients never reached this threshold. We
      conclude that pantoprazole significantly suppressed gastric acid secretion
      compared to omeprazole. Comparisons between pH and GAO showed that GAO was a more
      appropriate measure of gastric acid secretion than intragastric pH.

PMID- 16416225
TI  - Achalasia in a patient with adult-onset Tay-Sachs disease.

PMID- 16416226
TI  - Three-hour hydrogen breath test for assessing lactose malabsorption in clinical
      practice: to give 50 or 20 grams of lactose?

PMID- 16416227
TI  - Effect of high- and low-caloric mixed liquid meals on intestinal gas dynamics.
AB  - High-caloric meals can evoke postprandial abdominal complaints involving
      disturbances in intestinal gas balance. We aimed to determine the influence of
      the caloric content of meals on intestinal gas dynamics. Eight healthy subjects
      (five women, three men; age range, 25-43 years) underwent paired studies with low
      (1 kcal/min)- and high (3 kcal/min)-caloric meal infusion 35% fat, (45%
      carbohydrate, 20% protein) into the duodenum in random order and proximal jejunal
      gas infusion. Gas evacuation, perception, and abdominal girth were assessed. The
      low-caloric meal caused neither gas retention (-7 +/- 58 ml) nor girth changes (0
      +/- 0 mm). In contrast, the high-caloric meal led to significant gas retention
      (705 +/- 56 ml) and increased abdominal perimeter (7 +/- 1 mm; P < 0.001 vs. the
      low-caloric meal for both). Thus, a high caloric load of nutrients arriving at
      the duodenum modulates both intestinal gas transit and abdominal perimeter.

PMID- 16416228
TI  - Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal
      transit in healthy volunteers.
AB  - Although malabsorption of small amounts of fructose-sorbitol mixtures occurs
      frequently in healthy humans, insights into their effects on gastrointestinal
      motility are poor. The present study addresses the hypothesis that malabsorption
      of a fructose-sorbitol challenge changes the small intestinal transit rate.
      Eleven healthy volunteers participated in a double-blind crossover investigation.
      In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose
      and 5 g sorbitol as 10% solutions. As a radiolabeled marker, (99m)Tc
      diethylenetriaminepentaacetic acid was added to each test solution. Breath
      hydrogen and methane concentrations and gastrointestinal progress of the
      radiolabeled marker were followed for the next 6-hr period. Malabsorption of
      small amounts of the fructose-sorbitol mixture was evident in all subjects. The
      area under the gastric radioactivity-time curve after ingestion of glucose did
      not differ from that after ingestion of the fructose-sorbitol mixture (P =
      0.7897). However, the mouth-to-cecum transit of the radiolabeled marker was
      faster (P = 0.0033) and the percentage content of the marker in colon was higher
      after ingestion of the fructose-sorbitol mixture than after ingestion of glucose
      (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose
      sorbitol mixture accelerates small bowel transit.

PMID- 16416229
TI  - Cecostomy in children with defecation disorders.
AB  - Administration of antegrade enemas through a cecostomy is a therapeutic option
      for children with severe defecation disorders. The purpose of this study is to
      report our 4-year experience with the cecostomy procedure in 31 children with
      functional constipation (n = 9), Hirschsprung's disease (n = 2), imperforate anus
      (n = 5), spinal abnormalities (n = 8), and imperforate anus in combination with
      tethered spinal cord (n = 7). Data regarding complications, antegrade enemas
      used, symptoms, and quality of life were retrospectively obtained. Placement of
      cecostomy tubes was successful in 30 of 31 patients. Soiling episodes decreased
      significantly in children with functional constipation (P = 0.01), imperforate
      anus (P < 0.01), and spinal abnormalities (P = 0.04). Quality of life improved in
      patients with functional constipation and imperforate anus. No difference in
      complications was found between percutaneous and surgical placement. Use of
      antegrade enemas via cecostomy improved symptoms and quality of life in children
      with a variety of defecation disorders.

PMID- 16416231
TI  - Relapse of inflammatory bowel disease associated with use of nonsteroidal anti
      inflammatory drugs.
AB  - To determine whether an association exists between relapse in inflammatory bowel
      disease and use of nonsteroidal anti-inflammatory drugs (NSAIDs), a retrospective
      records review was conducted of patients with Crohn's disease, ulcerative
      colitis, or indeterminate colitis examined at an outpatient tertiary care center
      between July 17, 2000, and November 1, 2001. Extracted data collected during the
      patient's last visit included medication use, maintenance therapy, disease
      activity, and smoking status. Use of NSAIDs was defined as a daily dose or more
      of any type the month before relapse. Of 60 patients (22, relapse; 38,
      remission), 9 (41%) in relapse and 10 (26%) in remission used NSAIDs. Maintenance
      therapy varied from 68% (relapse) to 92% (remission). The adjusted odds ratio
      between medication use and relapse was 6.31 (95% confidence interval, 1.16-34.38;
      P = .03). Use of NSAIDs was associated with relapse. A prospective cohort study
      that corrects for maintenance therapy is needed to evaluate this relationship.

PMID- 16416230
TI  - Double-blind pilot study of mesalamine vs. placebo for treatment of chronic
      diarrhea and nonspecific colitis in immunocompetent HIV patients.
AB  - Chronic diarrhea and colitis are common in patients positive for human
      immunodeficiency virus (HIV) under highly active antiretroviral treatment
      (HAART). This prospective double-blind study explores the effect of mesalamine
      vs. placebo in HIV-positive patients. Thirteen HIV-infected patients with
      noninfectious chronic diarrhea and > 250 CD4+ cells/mm(3) were randomized to
      mesalamine (2.4 g/day; n = 9) or placebo (n = 4) for 6 weeks. Colonoscopy was
      performed at baseline and week 6, and biopsies were obtained to calculate the
      Biopsy Activity Index (BAI). Diarrhea was assessed at baseline and end of
      treatment using the Disease Activity Index (DAI). Patients and clinicians
      completed Patient Global Improvement index (PGI) and Clinical Global Improvement
      index (CGI) at weeks 2 and 6. Comparisons at week 6 were statistically
      significant between mesalamine and placebo groups for BAI (P = 0.03), DAI (P =
      0.007), PGI (P = 0.008), and CGI (P = 0.008). Furthermore, major improvements
      were documented in the mesalamine group at week 6 compared to baseline for all
      variables, whereas the placebo group did not have any. Mesalamine was effective
      for treatment of chronic diarrhea and moderate nonspecific colitis in HIV
      patients.

PMID- 16416232
TI  - Increased circulating concentrations of growth-related oncogene (GRO)-alpha in
      patients with inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory state associated with
      increased risk of intestinal cancers. The aim of this study is to examine serum
      concentrations of growth-related oncogene (GRO)-alpha, a cytokine with
      inflammatory and growth-regulatory properties, in patients with IBD. We measured
      serum concentrations of GRO-alpha in 60 patients with ulcerative colitis, 42
      patients with Crohn's disease, 16 patients with other colitides, 12 patients with
      colorectal cancer, and 40 normal subjects using an enzyme-linked immunosorbent
      assay. We then analyzed how the cytokine was related to clinical and laboratory
      variables. Serum GRO-alpha concentrations in patients with active IBD were
      significantly higher than those in patients with quiescent disease, which in turn
      were higher than those in normal controls. Concentrations in patients with active
      ulcerative colitis were higher than in patients with active Crohn's disease.
      Analysis of paired serum samples showed a decrease in GRO-alpha after initiation
      of therapy. Furthermore, serum GRO-alpha correlated well with laboratory markers
      of IBD activity. We conclude that GRO-alpha may have an important role in
      development of IBD, and might itself be used as a marker of activity.
      Manipulation of GRO-alpha function might prove therapeutically useful.

PMID- 16416234
TI  - Pneumatosis coli in the setting of severe ulcerative colitis: a case report.

PMID- 16416233
TI  - Flow cytometric analysis of expression of transforming growth factor-beta and
      glucocorticoid-induced tumor necrosis factor receptor on CD4(+) CD25(+) T cells
      of patients with inflammatory bowel disease.
AB  - To determine whether human CD4(+)CD25(+) cells express glucocorticoid-induced
      tumor necrosis factor receptor (GITR) and transforming growth factor-beta (TGF
      beta) and the difference in CD4(+)CD25(+) cells between patients with
      inflammatory bowel diseases and healthy subjects, peripheral blood lymphocytes
      were obtained from patients with ulcerative colitis (UC; n = 50), Crohn's disease
      (CD; n = 49), and healthy volunteers (control; n = 50) and flow cytometric
      analysis was performed. In control subjects, the expression of GITR on
      CD4(+)CD25(+) cells (41.8 +/- 10.5%) was significantly higher than on CD4(+)CD25(
      ) cells (11.1 +/- 7.4%). Similarly, TGF-beta expression on CD4(+)CD25(+) cells
      (5.3 +/- 4.6%) was higher than on CD4(+)CD25(-) cells (1.2 +/- 1.4%). There were
      no significant differences among UC, CD, and control in CD4(+)CD25(+)/CD4(+)
      ratio. However, there was a significant difference in the CD4(+)CD25(+) TGF
      beta+/CD4(+)CD25(+) ratio between active UC and inactive UC (2.7 +/- 2.6 and 7.2
      +/- 3.9%, respectively). The results suggest that TGF-beta is involved in the
      induction or sustained remission of UC.

PMID- 16416235
TI  - Recurrent abdominal pain: what determines medical consulting behavior?
AB  - Recurrent abdominal pain (RAP) is associated with increased health care visits
      and school absences. In adults suffering from functional pain, psychosocial
      factors determine illness behavior and we aimed to investigate its role among
      children. A community sample of 40 RAP consulters, 41 RAP nonconsulters, and 36
      pain-free controls and their mothers completed questionnaires on GI and non-GI
      symptoms, school absences, psychological symptoms, coping, self-esteem, and
      behavioral and cognitive responses to RAP. T-tests showed significant differences
      between RAP and controls in (1) GI and non-GI symptoms and school absences, (2)
      child distress and passive coping, and (3) mother's IBS severity, somatization,
      and fears about RAP. RAP consulters reported the same levels of GI symptoms and
      psychological distress as nonconsulters but missed significantly more school and
      their mothers reported more fears about RAP. Severity of symptoms and
      psychological distress did not predict consulting behavior. Only maternal fears
      about abdominal symptoms differentiated consulters from nonconsulters.

PMID- 16416237
TI  - Differing clinical manifestations of celiac disease transmitted by bone marrow
      transplantation.

PMID- 16416238
TI  - Liver dysfunction after a gluten-free diet in a patient with celiac disease: a
      new link?

PMID- 16416236
TI  - Intestinal T cell responses to cereal proteins in celiac disease.
AB  - Celiac disease is caused by sensitivity to wheat gluten in genetically
      susceptible individuals. The etiological role of the other wheat-related cereals,
      barley, rye, and oats, is still debated. In order to investigate this issue
      further, in this study we examined the immune response of celiac mucosal T cell
      lines to fractions from all four cereals. Cell stimulation was assessed by
      measuring proliferation (employing (3)H-thymidine incorporation) or cytokine (IL
      2, IFN-gamma) production. All five T cell lines demonstrated immunoreactivity to
      protein fractions from the four related cereals. In some cell lines, reactivity
      to wheat, barley, and rye was only evident when these cereal fractions had been
      pretreated with tissue transglutaminase. This study confirms the similar T cell
      antigenic reactivity of these four related cereals and has implications for their
      exclusion in the gluten-free diet. However, despite oats stimulation of T cell
      lines, this cereal does not activate a mucosal lesion in most celiac patients.

PMID- 16416239
TI  - Acute abdomen associated with schistosomiasis of the appendix.

PMID- 16416240
TI  - Racial differences in epidemiology of irritable bowel syndrome alone, un
      investigated dyspepsia alone, and "overlap syndrome" among african americans
      compared to Caucasians: a population-based study.
AB  - There is A paucity of data on racial differences in epidemiology of irritable
      bowel syndrome (IBS) alone and un-investigated dyspepsia (UD) alone compared to
      "overlap syndrome" (OS). We conducted a random survey (n = 990). Subjects
      completed a questionnaire which included Rome II criteria for IBS and functional
      dyspepsia (FD). Among African Americans, the prevalence of IBS alone, UD alone,
      and OS was 0.6%, 17%, and 7.3%, respectively. It was 0%, 13%, and 13% among
      Caucasian Americans. All but four patients with IBS had UD. Among patients with
      UD, OS was seen in 30% of African Americans, compared to 50% among Caucasian
      Americans. Among African Americans, UD patients were younger compared to OS
      patients. African Americans with UD were more likely than OS patients to have
      children. Marital status, education, and household income were not a factor among
      Caucasians. African Americans patients below poverty level were more likely to
      have UD than OS (22% vs 10%). Considering patients with UD alone, race, age, sex,
      marital status, number of children, education, and income level were not
      different between African Americans and Caucasians. Compared to African
      Americans, Caucasians with OS were likely to be married and live in an urban
      area. There was a higher prevalence of OS among Caucasians with lower education.
      OS is 2.5 times more likely to occur among Caucasians compared to African
      Americans. We conclude that OS is more common among Caucasians than African
      Americans. IBS and OS are virtually synonymous.

PMID- 16416243
TI  - Change in children's emotional and behavioural problems over a one-year period:
      Associations with parental problem recognition and service use.
AB  - Although children with emotional or behavioural problems are at increased risk of
      future problems, knowledge of factors associated with persistence and change in
      child problems, once these problems exist, is limited. Using repeated measures
      analyses of variance, the present study investigated the association of parental
      problem recognition, professional and informal service use, and sociodemographic
      factors with change in child problems over a one-year period, in a sample of 360
      children and adolescents with emotional and behavioural problems. Higher overall
      problem levels were found in children (aged 4-11 years at baseline) versus
      adolescents (aged 12-17 years), in boys, and in children with less educated
      parents, which indicates the need to address preventive actions at these groups.
      Although rates of service use were low, children who had been in contact with
      general practitioners or mental health services had higher overall problem
      levels, suggesting that children who need it most end up receiving professional
      care. Although child emotional and behavioural problems decreased significantly
      over time, this change was not associated with utilisation of professional or
      informal services. Our findings imply the need for methodologically sound
      research into the effectiveness of professional and informal services for child
      emotional and behavioural problems.

PMID- 16416241
TI  - The efficacy of octreotide in pancreatic and intestinal changes: radiation
      induced enteritis in animals.
AB  - Radiation enteritis occurs during the radiotherapy of many intraabdominal
      malignancies. Radiation induces cellular injury directly and through the
      generation of free radicals. In the present study we aimed to investigate the
      effect of octreotide (OCT) pretreatment in irradiation-induced enteritis. For
      this aim, rats were injected with 50 microg/kg OCT 4 days before irradiation and
      continued for 3 more days, until sacrifice. Then intestinal and pancreatic
      myeloperoxidase (MPO) activities and intestinal malondialdehyde (MDA) levels of
      the rats were measured. Irradiation significantly increased intestinal and
      pancreatic MPO activities and MDA levels of intestinal tissues in comparison to
      those of the sham group. OCT treatment improved this elevation. The
      histopathologic evaluation of the mucosal structure was also preserved in the OCT
      treated group. Inflammation of pancreatic tissue was also confirmed with
      histopathological examinations. In the irradiation group, NFkappa-B
      overexpression was detected. OCT treatment decreased the end organ damage and
      inflammation of the small intestine. In conclusion, OCT appears to have
      beneficial effects on intestinal and pancreatic damage in abdominal irradiation
      through the inflammatory process.

PMID- 16416244
TI  - Easy access echocardiography for the general practitioner: results from the
      Parkstad area in the Netherlands.
AB  - Heart failure has a low incidence in general practice but is not easy to
      recognize in this setting. Frequently a normal electrocardiogram and a normal
      level of brain natriuretic peptide can exclude heart failure as a cause for
      dyspnea. Unfortunately the positive predictive value of both techniques is low.
      Imaging with echocardiography can then give the clue to the correct diagnosis.
      Also correct diagnosis of cardiac murmurs is not easy in general practice.
      Therefore an open access echocardiographic service was established in the south
      of the Netherlands. According to the existing services in the United Kingdom
      general practitioners in this area were able to ask for an echocardiogram without
      referring the patient to the cardiologist. During a period of 19 months 131
      patients were referred to the Centre of Medical Diagnostics for an
      echocardiogram. In 12% of the patients referred for dyspnea a left ventricular
      ejection fraction lower than 40% was found. Fourty nine percent of the patients
      had diastolic dysfunction. In 33% heart failure could be excluded. In 62% of the
      patients referred for a cardiac murmur cardiac pathology could be found. In 38%
      of the patients the cardiac murmur could be established as a functional murmur.
      The service was found to improve practice by most of the general practitioners.

PMID- 16416246
TI  - Glass transition and the origin of poly(p-phenylene sulfide) secondary
      crystallization.
AB  - The effect of low temperature cold-crystallization on quenched poly(p-phenylene
      sulfide) (PPS) amorphous phase behaviour was systematically investigated by
      differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis
      (DMTA) over the entire range of the process, from its early stage to the end. For
      the first time a well resolved double glass transition of partially cold
      crystallized samples was evidenced. A T(g) steady increase was observed during
      the primary crystallization process, due to the reduction of amorphous chain
      segmental mobility imposed by the growing rigid phase. A shift of the relaxation
      temperature of about 10 degrees C was recorded at the end of the primary
      crystallization process. As the secondary crystallization takes place a new glass
      transition appears at higher temperature. For longer annealing time the lower
      T(g) disappears while the intensity of the upper one increases. The upper
      temperature glass transition of semi-crystalline PPS is explained as a
      consequence of the PPS secondary cold-crystallization process. In the light of
      the thermal and dynamic mechanical results, an interpretation is given of step
      wise double crystallization, evidenced in non-isothermal cold-crystallization
      experiments carried out at low heating rate and followed by means of FT-IR
      techniques.

PMID- 16416245
TI  - Automated QSPR through Competitive Workflow.
AB  - This paper describes a novel software architecture, Competitive Workflow, which
      implements workflow as a distributed and competitive multi-agent system. The
      implementation of a competitive workflow architecture designed to model important
      computer-aided molecular design workflows, the Discovery Bus, is described. QSPR
      modelling results for three example ADME datasets, for solubility, human plasma
      protein binding and P-glycoprotein substrates using an autonomous QSPR modelling
      workflow implemented on the Discovery Bus are presented. The autonomous QSPR
      system allows exhaustive exploration of descriptor and model space, automated
      model validation and continuous updating as new data and methods are made
      available. Prediction of properties of novel structures by an ensemble of models
      is also a feature of the system.

PMID- 16416247
TI  - Commentary on the observations of solid-like rheological response in unentangled
      polymer melts by H. Mendil, P. Baroni, L. Noirez, D. Collin, P. Martinoty.

PMID- 16416249
TI  - Drainage induced convection rolls in foams I. Convective bubble motion in a
      tilted tube.
AB  - When liquid is added to a foam at sufficiently large flow rates, convective
      bubble motion will occur. Experiments are described in which the foam is confined
      in a tube which is tilted from the vertical. The theory of foam drainage is
      applied to this problem to show that the critical angle of tilt theta(c) at which
      convection occurs is related to the liquid flow-rate Q by theta(c) proportional
      to Q(-3/4).

PMID- 16416250
TI  - Commentary on "Solid-like rheological response of non-entangled polymers in the
      molten state" by H. Mendil et al.
AB  - We discuss the rheology experiments on classical and liquid crystal polymer melts
      by Mendil et al., in the light of the old and new piezorheometry experiments we
      have carried out on both types of melt. The mechanical behavior we have observed
      in the linear and non-linear regimes are independent of the melt studied
      (classical or liquid crystal), and of their nature (siloxane-type, acrylate-type
      and styrene-type). In the linear regime, the mechanical behavior of the melts
      presents two components: the first one is the conventional contribution. It is
      due to polymer chains, and is independent of sample thickness. The second one,
      which can be observed only when a strong interaction between the compound and the
      substrate exists, is associated with the glass transition. This component
      displays an elastic response depending on the sample thickness, and disappears at
      high temperature. It can be explained by assuming the presence of long-range
      density fluctuations, which are associated with the glass transition, and frozen
      at the frequencies used in the experiments. The experiments as a function of the
      applied strain show that the value of the elastic component decreases when the
      applied strain increases. This slipping transition occurs progressively, which
      highlights the heterogeneous nature of the anchoring. The results on the
      classical polymer by Mendil et al. can be considered to be consistent with ours.
      In contrast, their results on the liquid crystal polymer differ markedly from
      ours, showing that the elastic response of this sample has not the same origin.

PMID- 16416251
TI  - A multiscale molecular dynamics approach to contact mechanics.
AB  - The friction and adhesion between elastic bodies are strongly influenced by the
      roughness of the surfaces in contact. Here we develop a multiscale molecular
      dynamics approach to contact mechanics, which can be used also when the surfaces
      have roughness on many different length-scales, e.g., for self affine fractal
      surfaces. As an illustration we consider the contact between randomly rough
      surfaces, and show that the contact area varies linearly with the load for small
      load. We also analyze the contact morphology and the pressure distribution at
      different magnification, both with and without adhesion. The calculations are
      compared with analytical contact mechanics models based on continuum mechanics.

PMID- 16416253
TI  - Screened electrostatics of charged particles on a water droplet.
AB  - We study the electrostatic properties of charged particles trapped at an
      interface in a water-in-oil microemulsion. The electrostatic potential and the
      counterion distribution in the water droplet are given in terms of the ratio of
      the Debye screening length kappa(-1) and the droplet radius R. In the limit R-
      >infinity we recover the well-known results for a flat interface. Finite-size
      corrections are obtained in terms of the small parameter 1/kappaR. Part of the
      counterions spread along the interface and form a charged layer of one Debye
      length thickness. In particular, there is a uniform surface charge contribution.
      We derive explicit expressions for the electric field, the mobile charge density,
      and the charge-induced pressure on the interface.

PMID- 16416254
TI  - The immunity of polymer-microemulsion networks.
AB  - The concept of network immunity, i.e., the robustness of the network connectivity
      after a random deletion of edges or vertices, has been investigated in biological
      or communication networks. We apply this concept to a self-assembling, physical
      network of microemulsion droplets connected by telechelic polymers, where more
      than one polymer can connect a pair of droplets. The gel phase of this system has
      higher immunity if it is more likely to survive (i.e., maintain a macroscopic,
      connected component) when some of the polymers are randomly degraded. We consider
      the distribution p(sigma) of the number of polymers between a pair of droplets,
      and show that gel immunity decreases as the variance of p(sigma) increases.
      Repulsive interactions between the polymers decrease the variance, while
      attractive interactions increase the variance, and may result in a bimodal
      p(sigma).

PMID- 16416255
TI  - Commentary on rheology of polymers in narrow gaps.

PMID- 16416256
TI  - A risk profile for identifying community-dwelling elderly with a high risk of
      recurrent falling: results of a 3-year prospective study.
AB  - INTRODUCTION: The aim of the prospective study reported here was to develop a
      risk profile that can be used to identify community-dwelling elderly at a high
      risk of recurrent falling. MATERIALS AND METHODS: The study was designed as a 3
      year prospective cohort study. A total of 1365 community-dwelling persons, aged
      65 years and older, of the population-based Longitudinal Aging Study Amsterdam
      participated in the study. During an interview in 1995/1996, physical, cognitive,
      emotional and social aspects of functioning were assessed. A follow-up on the
      number of falls and fractures was conducted during a 3-year period using fall
      calendars that participants filled out weekly. Recurrent fallers were identified
      as those who fell at least twice within a 6-month period during the 3-year follow
      up. RESULTS: The incidence of recurrent falls at the 3-year follow-up point was
      24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87
      fractures that resulted from a fall, including 20 hip fractures, 21 wrist
      fractures and seven humerus fractures. Recurrent fallers were more prone to have
      a fall-related fracture than those who were not defined as recurrent fallers
      (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis
      identified the following predictors in the risk profile for recurrent falling:
      two or more previous falls, dizziness, functional limitations, weak grip
      strength, low body weight, fear of falling, the presence of dogs/cats in the
      household, a high educational level, drinking 18 or more alcoholic consumptions
      per week and two interaction terms (high education x 18 or more alcohol
      consumptions per week and two or more previous falls x fear of falling)
      (AUC=0.71). DISCUSSION: At a cut-off point of 5 on the total risk score (range 0
      30), the model predicted recurrent falling with a sensitivity of 59% and a
      specificity of 71%. At a cut-off point of 10, the sensitivity and specificity
      were 31% and 92%, respectively. A risk profile including nine predictors that can
      easily be assessed seems to be a useful tool for the identification of community
      dwelling elderly with a high risk of recurrent falling.

PMID- 16416257
TI  - Duloxetine treatment for women awaiting continence surgery.
AB  - The study assessed the effect of offering a 4-week course of duloxetine therapy
      to 73 women awaiting a tension-free vaginal tape (TVT) operation. Twenty-seven
      women (37%) declined taking the drug, leaving 46 women (63%) willing to take drug
      therapy. Thirteen women were scheduled for a TVT with concurrent prolapse
      surgery, and 1 of these women decided that she no longer needed the surgery.
      Eight of the 33(24%) women scheduled for a TVT without concurrent prolapse
      surgery came off the waiting list. Nine women of the 33 women scheduled for a TVT
      without concurrent surgery (27%) found that the medication did not work
      sufficiently well. Sixteen of the 33 women (48%) discontinued medication due to
      side-effects. Women on a waiting list for surgery may be unwilling to take
      duloxetine therapy and less tolerant of side-effects.

PMID- 16416258
TI  - A lifetime of metabolism.

PMID- 16416260
TI  - Endothelial nitric oxide synthase: insight into cell-specific gene regulation in
      the vascular endothelium.
AB  - The vascular endothelium plays a crucial role in regulating normal blood vessel
      physiology. The gene products responsible are commonly expressed exclusively, or
      preferentially, in this cell type. However, despite the importance of regulated
      gene expression in the vascular endothelium, relatively little is known about the
      mechanisms that restrict endothelial-specific gene expression to this cell type.
      While significant progress has been made towards understanding the regulation of
      endothelial genes through cis/trans paradigms, it has become apparent that
      additional mechanisms must also be operative. For example, chromatin-based
      mechanisms, including cell-specific DNA methylation patterns and post
      translational histone modifications, have recently been demonstrated to play
      important roles in the cell-specific expression of endothelial nitric oxide
      synthase (eNOS). This review investigates the involvement of epigenetic
      regulatory mechanisms in vascular endothelial cell-specific gene expression using
      eNOS as a prototypical model, and will address the possible contributions of
      these pathways to diseases of the vasculature.

PMID- 16416259
TI  - Size matters: a view of selenocysteine incorporation from the ribosome.
AB  - This review focuses on the known factors required for selenocysteine (Sec)
      incorporation in eukaryotes and highlights recent findings that have compelled us
      to propose a new model for the mechanism of Sec incorporation. In light of this
      data we also review the controversial aspects of the previous model specifically
      regarding the proposed interaction between SBP2 and eEFSec. In addition, the
      relevance of two recently discovered factors in the recoding of Sec are reviewed.
      The role of the ribosome in this process is emphasized along with a detailed
      analysis of kinkturn structures present in the ribosome and the L7Ae RNA-binding
      motif present in SBP2 and other proteins.

PMID- 16416264
TI  - Death of neuronal clusters contributes to variance of age at onset in
      Huntington's disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disease caused by an
      expanded polyglutamine (polyQ) repeat in the protein huntingtin. Due to selective
      neuronal loss in the cortex and striatum, HD patients develop various movement
      disturbances, psychological changes, and dementia. Symptoms usually appear in
      individuals between 30 and 50 years of age. The principal cause of variability of
      age at onset (AO) is the length of the polyQ repeat. Several additional genetic
      factors contributing to the variance have been identified. At least 35% of the
      variance, however, remains unexplained. Using a stochastic model, we show that
      the pattern of cell death of striatal neurons might contribute up to 20% of
      variance of AO.

PMID- 16416265
TI  - PLP1 and GPM6B intragenic copy number analysis by MAPH in 262 patients with
      hypomyelinating leukodystrophies: Identification of one partial triplication and
      two partial deletions of PLP1.
AB  - The proteolipid protein 1 (PLP1) gene is known to be mutated in the X-linked
      disorders of myelin formation Pelizaeus-Merzbacher disease (PMD) and spastic
      paraplegia type 2. The most commonly found PLP1 mutations are gene duplications
      (60-70%) and point mutations (20%). About 20% of patients with a PMD phenotype do
      not present identified PLP1 mutation, thus suggesting genetic heterogeneity
      and/or undetected PLP1 abnormalities. Except the recently described MLPA
      screening the seven exonic regions, the currently used techniques to quantify
      PLP1 gene copy number do not investigate small intragenic PLP1 rearrangements.
      Using the multiplex amplifiable probe hybridization (MAPH) technique, we looked
      simultaneously for intragenic rearrangements along the PLP1 gene (exonic and
      regulatory regions) and for rearrangements in the GPM6B candidate gene (a member
      of the proteolipid protein family). We tested 262 hypomyelinating patients: 56
      PLP1 duplicated patients, 1 PLP1 triplicated patient, and 205 patients presenting
      a leukodystrophy of undetermined origin with brain MRI suggesting a defect in
      myelin formation. Our results show that MAPH is an alternative reliable technique
      for diagnosis of PLP1 gene copy number. It allows us (1) to demonstrate that all
      PLP1 duplications previously found encompass the whole gene, (2) to establish
      that copy number changes in GPM6B and intragenic duplications of PLP1 are very
      unlikely to be involved in the etiology of UHL, and (3) to identify one partial
      triplication and two partial deletions of PLP1 in patients presenting with a PMD
      phenotype.

PMID- 16416266
TI  - Lipid-lowering actions of imidazoline antihypertensive agents in metabolic
      syndrome X.
AB  - Agonists active at I1-imidazoline receptors (I1R) not only lower blood pressure
      but also ameliorate glucose intolerance, insulin resistance, and hyperlipidemia
      with long-term treatment. We sought to determine the possible mechanism for the
      lipid-lowering actions of imidazolines in a model of metabolic Syndrome X, the
      spontaneously-hypertensive obese (SHROB) rat. The acute actions of moxonidine and
      rilmenidine, selective I1R agonists, were compared to a specific alpha2
      adrenergic receptor agonist, guanabenz, with and without selective receptor
      blockers. Moxonidine and rilmenidine rapidly reduced plasma triglyceride (20+/-4%
      and 21+/-5%, respectively) and cholesterol (29+/-9% and 27+/-9%). In contrast,
      the specific alpha2-adrenergic receptor agonist guanabenz failed to reduce plasma
      lipids. Blocking experiments showed that moxonidine's actions were mediated by
      I1R and not alpha2-adrenergic receptors. To evaluate a hepatic site of action,
      radioligand binding studies with liver plasma membranes confirmed the presence of
      I1R. Intraportal moxonidine reduced plasma triglycerides by 23+/-3% within 10
      min. Moxonidine inhibited hepatic triglyceride secretion by 75% compared to
      vehicle treatment. Tracer studies with 2H2O suggested that moxonidine inhibits de
      novo fatty acid synthesis. Thus, activation of I1R lowers plasma lipids, with the
      main site of action probably within the liver to reduce synthesis and secretion
      of triglycerides. More selective I1R agonists might provide monotherapy for
      hyperlipidemic hypertension.

PMID- 16416268
TI  - Evaluation of a novel kit for the rapid detection of extended-spectrum beta
      lactamases.
AB  - Since a method of rapidly detecting extended-spectrum beta-lactamase (ESBL)
      production in gram-negative isolates from patients with severe infection is
      urgently required, the present study of a novel commercial kit was conducted. The
      Cica-Beta Test I (Kanto Chemical, Tokyo, Japan) is designed for the rapid
      detection of ESBL in gram-negative bacteria directly from isolated colonies in a
      15-min protocol. In this study, a total of 304 strains of Klebsiella spp.,
      Escherichia coli and Proteus mirabilis were tested using the novel kit and the
      phenotypic confirmatory disk test using cefotaxime and ceftazidime with and
      without clavulanate. The kit showed 95.5 and 98.1% sensitivity and specificity,
      respectively, as compared to the disk test, and thus proved to be an appropriate
      tool for the rapid detection of ESBL.

PMID- 16416269
TI  - Critical comment: analyzing the effect of novel therapies on cytokine expression
      in inflammatory bowel disease: do cytokine levels reflect clinical response?
AB  - Over the past several years, research in the field of cytokine production and
      function has become indispensable to understand the immunopathology of chronic
      intestinal inflammation. Thereupon, clinical studies analyzing cytokine
      production have generated a tremendous amount of data. In patients with
      inflammatory bowel disease, several studies examined pro-inflammatory cytokines
      in gut tissue and plasma, but a clear interpretation of the results with respect
      to disease activity or therapeutic response has been hampered by patient- and
      sample-related pitfalls.

PMID- 16416267
TI  - Diagnosis of invasive aspergillosis and mucormycosis in immunocompromised
      patients by seminested PCR assay of tissue samples.
AB  - Aspergillosis and mucormycosis are the most common mold infections in patients
      with hematological malignancies. Infections caused by species of the genus
      Aspergillus and the order Mucorales require different antifungal treatments
      depending on the in vitro susceptibility of the causative strain. Cultures from
      biopsy specimens frequently do not grow fungal pathogens, even from
      histopathologically proven cases of invasive fungal infection. Two seminested PCR
      assays were evaluated by amplifying DNA of zygomycetes and Aspergillus spp. from
      organ biopsies of 21 immunocompromised patients. The PCR assays correctly
      identified five cases of invasive aspergillosis and six cases of mucormycosis.
      They showed evidence of double mold infection in two cases. Both assays were
      negative in five negative controls and in two patients with yeast infections.
      Sequencing of the PCR products was in accordance with culture results in all
      culture-positive cases. In six patients without positive cultures but with
      positive histopathology, sequencing suggested a causative organism. Detection of
      fungal DNA from biopsy specimens allows rapid identification of the causative
      organism of invasive aspergillosis and mucormycosis. The use of these PCR assays
      may allow guided antifungal treatment in patients with invasive mold infections.

PMID- 16416270
TI  - New complete orthonormal sets of hyperspherical harmonics and their one-range
      addition and expansion theorems.
AB  - In this study, the complete orthonormal sets of phi(alpha)-momentum space
      orbitals (where alpha = 1, 0, -1, -2, ...) obtained from the psi(alpha)-ETO in
      coordinate representation (I.I. Guseinov, J. Mol. Model., 9 (2003) 135) are
      reduced to the complete orthonormal sets of hyperspherical harmonics (HSH) by
      means of a Fock transformation of the radial momentum to an angular variable. It
      is shown that the group of transformations is the four-dimensional rotation group
      O(4) and, therefore, the HSH presented in this work are the complete orthonormal
      sets of functions. For these functions, the one-range addition and expansion
      theorems are obtained. The formulae for HSH and their addition and expansion
      theorems derived in this work can be used to evaluate the multicenter integrals
      that arise when exponential-type basis functions are used in atomic and molecular
      calculations.

PMID- 16416273
TI  - Female hydrocele of the canal of Nuck: a case report.
AB  - The processus vaginalis is an evagination of parietal peritoneum which
      accompanies the round ligament through the inguinal ring into the inguinal canal.
      The portion of processus vaginalis within the inguinal canal in women is called
      'the canal of Nuck'. When the processus vaginalis fails to close, it can result
      in a hernia or hydrocele, both in women and men. Female hydrocele of the canal of
      Nuck is uncommon. A literature search revealed that little has been published on
      this condition. We present a case of a hydrocele of the canal of Nuck in a 5
      month-old female infant.

PMID- 16416272
TI  - Direct regulation of insulin secretion by angiotensin II in human islets of
      Langerhans.
AB  - AIMS/HYPOTHESIS: This study aimed to identify the expression of angiotensin II
      receptors in isolated human islets and beta cells and to examine the functional
      consequences of their activation. MATERIALS AND METHODS: Single-cell RT-PCR was
      used to identify whether human islet cells express mRNA for type 1 angiotensin II
      receptors (AT(1)), and western blotting was used to determine AT(1) protein
      expression by human islets and MIN6 beta cells. We measured changes in
      intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and
      human islet cells. Dynamic insulin secretory responses were determined by RIA
      following perifusion of human islets and MIN6 cells. RESULTS: Human islets
      expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for
      angiotensin-converting enzyme. In addition, human and mouse beta cells expressed
      AT(1). These were functionally coupled to increases in intracellular calcium,
      which occurred at least in part through phospholipase-C-sensitive mechanisms and
      calcium influx through voltage-operated calcium channels. Short-term exposure of
      human islets and MIN6 cells to angiotensin II caused a rapid, short-lived
      initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin
      secretion induced by glucose (at 8 and 16.7 mmol/l). CONCLUSIONS/INTERPRETATION:
      These data demonstrate that the AT(1) is expressed by beta cells and that
      angiotensin II effects a short-lived and direct stimulation of human and mouse
      beta cells to promote insulin secretion, most probably through elevations in
      intracellular calcium. Locally produced angiotensin II may be important in
      regulating a coordinated insulin secretory response from beta cells.

PMID- 16416274
TI  - The carina as a landmark for central venous catheter placement in small children.
AB  - Central venous devices are frequently used in children to monitor haemodynamic
      status, to administer fluids, medication, parenteral nutrition and for blood
      sampling. Life-threatening complications that may occur on insertion if the
      central venous catheter (CVC) is misplaced, are cardiac tamponade or a hydro
      /haemopericardium. There is still controversy over the optimum catheter tip
      position in paediatric patients, whether to place the CVC tip in the superior
      vena cava, outside the pericardial boundaries or in the right atrium. However,
      the exact location of the pericardium cannot be seen on a normal chest x-ray. The
      carina is a radiographic marker for CVC placement, suggested on the basis of
      studies with conserved and fresh adult cadavers. In order to confirm this
      landmark for children, the present study was performed with 31 fresh cadavers of
      small children (mean age 12.5+/-3.4 months) that had been selected for autopsy in
      the Institute of Legal Medicine. Results clearly demonstrate that the carina was
      0.5+/-0.04 cm above the pericardial duplication as it transversed the SVC. In no
      infant cadaver was the carina inferior to the pericardium. Thus, the results are
      analogous to those in adults and confirm that the carina is a simple anatomical
      radiological landmark, superior to the pericardial reflection, that can be used
      to identify the placement of CVC even in newborn and small children.

PMID- 16416271
TI  - Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through
      protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of
      apoptosis.
AB  - AIMS/HYPOTHESIS: Benfotiamine, a vitamin B1 analogue, reportedly prevents
      diabetic microangiopathy. The aim of this study was to evaluate whether
      benfotiamine is of benefit in reparative neovascularisation using a type I
      diabetes model of hindlimb ischaemia. We also investigated the involvement of
      protein kinase B (PKB)/Akt in the therapeutic effects of benfotiamine. METHODS:
      Streptozotocin-induced diabetic mice, given oral benfotiamine or vehicle, were
      subjected to unilateral limb ischaemia. Reparative neovascularisation was
      analysed by histology. The expression of Nos3 and Casp3 was evaluated by real
      time PCR, and the activation state of PKB/Akt was assessed by western blot
      analysis and immunohistochemistry. The functional importance of PKB/Akt in
      benfotiamine-induced effects was investigated using a dominant-negative
      construct. RESULTS: Diabetic muscles showed reduced transketolase activity, which
      was corrected by benfotiamine. Importantly, benfotiamine prevented ischaemia
      induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored
      endothelium-dependent vasodilation. Histological studies revealed the improvement
      of reparative neovascularisation and the inhibition of endothelial and skeletal
      muscle cell apoptosis. In addition, benfotiamine prevented the vascular
      accumulation of advanced glycation end products and the induction of pro
      apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in
      ischaemic muscles. The benefits of benfotiamine were nullified by dominant
      negative PKB/Akt. In vitro, benfotiamine stimulated the proliferation of human
      EPCs, while inhibiting apoptosis induced by high glucose. In diabetic mice, the
      number of circulating EPCs was reduced, with the deficit being corrected by
      benfotiamine. CONCLUSIONS/INTERPRETATION: We have demonstrated, for the first
      time, that benfotiamine aids the post-ischaemic healing of diabetic animals via
      PKB/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. In
      addition, benfotiamine combats the diabetes-induced deficit in endothelial
      progenitor cells.

PMID- 16416275
TI  - CAD for mammography: the technique, results, current role and further
      developments.
AB  - CAD systems, developed to assist the radiologist in the detection of suspicious
      lesions on mammograms, are currently controversially discussed. The highly
      sensitive detection of malignant structures including priors by CAD is linked
      with a low specific performance and a high rate of falsely positive markings.
      This causes controversial results regarding the effect of CAD systems for the
      diagnosing radiologist. This review aims to give an overview of the current
      literature, to state the currently discussed controversial results of CAD and to
      give an outlook on the next developments, which are not limited to senology, but
      include many other applications of CAD systems in radiology.

PMID- 16416277
TI  - The lucent rim: a radiographic and computed tomography sign of Paget's disease of
      the skull.
AB  - In seven of eight patients with osteoporosis circumscripta of the cranial vault,
      the pagetic bone lacunae were separated from the normal bone by a lucent rim
      visible on conventional radiographs and computed tomography scans. The contour of
      the rim was sharp on the side of the healthy surrounding bone and hazy on the
      side of the defect. To our knowledge, this sign has been reported in one single
      previous article dealing with two pagetic patients with the bisphosphonate escape
      phenomenon.

PMID- 16416276
TI  - Preoperative staging of rectal cancer: accuracy of 3-Tesla magnetic resonance
      imaging.
AB  - The purpose of this study was to evaluate the accuracy of 3-Tesla magnetic
      resonance imaging (MRI) for the preoperative staging of rectal cancer. Thirty
      five patients with a primary rectal cancer who underwent preoperative 3-T MRI
      using a phased-array coil and had a surgical resection were enrolled in the study
      group. Preoperatively, three experienced radiologists independently assessed the
      T and N staging. A confidence level scoring system was used to determine if there
      was any perirectal invasion, and receiver operating characteristic (ROC) curves
      were generated. The interobserver agreement was estimated using kappa statistics.
      The overall accuracy rate of T staging for rectal cancer was 92%. The diagnostic
      accuracy was 97% for T1, 89% for T2 and 91% for T3, respectively. The predictive
      accuracy for perirectal invasion by the three observers was high (Az>0.92). The
      interobserver agreement for T staging was moderate to substantial. The overall
      sensitivity, specificity, and accuracy for the detection of mesorectal nodal
      metastases were 80%, 98%, and 95%, respectively. In conclusion, preoperative 3-T
      MRI using a phase-array coil accurately indicates the depth of tumor invasion for
      rectal cancer with a low variability.

PMID- 16416278
TI  - Long-term follow-up of surgically excluded popliteal artery aneurysms with multi
      slice CT angiography and Doppler ultrasound.
AB  - The purpose of this study was to evaluate the role of multi-slice computed
      tomography (MSCT) angiography in the follow-up of popliteal artery aneurysms
      (PAAs) that have been operated on. Aneurysm exclusion and progression, graft
      patency and graft-related complications were analyzed. Fourteen patients with 21
      surgically excluded PAAs were evaluated with MSCT angiography with slice
      thickness of 1.25 mm. The mean follow-up time was 67 months. MSCT demonstrated
      blood flow in six non-excluded PAAs (24%), with an average increase in the
      diameter of 21 mm over time. Fifteen PAAs demonstrated no blood flow and revealed
      an average decrease of 7 mm in diameter. The origin of this residual perfusion
      was demonstrated, and collaterals were involved in five of six non-excluded PAAs.
      In addition, MSCT demonstrated three graft stenoses. Furthermore, two occluded
      grafts were visualized. Twenty-four percent of the patients after surgical
      exclusion of PAAs revealed residual perfusion within the aneurysmal sac during
      follow-up, with a significant increase in the aneurysmal size with MSCT.
      Moreover, evaluation of the graft patency could also be done as could
      demonstration of anastomotic abnormalities. Thus, MSCT might be considered as a
      new tool to evaluate residual collateral feeding of popliteal aneurysmal sac and
      could be useful in identification and localization of feeding vessels.

PMID- 16416279
TI  - A multicenter reproducibility study of single-voxel 1H-MRS of the medial temporal
      lobe.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) has provided evidence for a
      reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in
      cerebral disorders such as Alzheimer's Disease. Within the (1)H-MRS study of the
      German Research Network on Dementia, we determined the multicenter
      reproducibility of single-voxel (1)H-MRS of the MTL. At five sites with 1.5T MR
      systems, single-voxel (1)H spectra from the MTL of an identical healthy subject
      were measured. The same subject was also examined at one of the sites five times
      to assess intracenter stability. The protocol included water-suppressed spectra
      with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification
      of metabolite concentrations. The intracenter reproducibility of absolute NAA
      concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the
      concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the
      ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for
      NAA and were below 10% for all other metabolites and metabolic ratios. Our study
      demonstrates that quantitative assessment of NAA with single-voxel MRS can be
      performed with high intercenter reproducibility. This is the basis for applying
      (1)H-MRS in large-scale early recognition and treatment studies in MTL affecting
      disorders.

PMID- 16416280
TI  - Exploratory laparoscopy for recurrent right lower quadrant pain in a pediatric
      population.
AB  - Recurrent or chronic abdominal pain can be a challenging problem when
      conventional diagnostic studies fail to identify the cause. It is estimated that
      up to one-third of children suffer from abdominal pain, and in this population
      recurrent pain can be even more challenging. Although recurrent right lower
      quadrant (RLQ) or periumbilical pain may be attributed to chronic appendicitis,
      this diagnosis remains controversial. Our aim was to evaluate pediatric patients
      who had undergone laparoscopic exploration for chronic RLQ abdominal pain to
      determine their histologic diagnosis, etiology of pain, and contributing factors
      that may predict a positive outcome. Patients with abdominal pain greater than 1
      month in duration who ultimately underwent laparoscopic exploration and
      appendectomy were included in the study. Patients were excluded if an identified
      source of pain was discovered during preoperative workup, or if postoperative
      follow-up was less than 2 years. Intraoperative findings were noted, and all
      specimens were histologically examined with additional, subsequent independent
      review. Pertinent findings from preoperative diagnostic tests, mental health
      history, and pre and postoperative symptomatology were noted. Patient outcomes
      were recorded at the time of follow-up and after 2 years to assess resolution of
      their symptoms. Of the 44 patients studied, 31 (70.5%) had partial or complete
      resolution of symptoms at 2 years. Thirteen (29.5%) continued to have pain.
      Twenty-eight patients (63.6%) had abnormal histology identified on appendiceal
      examination, and 14 had other abnormalities found at laparoscopy (31.8%).
      Eighteen patients were being treated for psychiatric diagnosis, and 21 suffered
      from chronic headaches. There were no long-term complications from surgery. Long
      term follow-up revealed that 70% reported complete or partial relief of their RLQ
      pain at 2 years. No factors were identified that may be helpful in predicating
      outcome in this population. While exploration was beneficial for a majority of
      this population, patients and parents should be warned that this intervention
      might not provide the relief of symptoms or provide the diagnostic answer to
      their pain.

PMID- 16416281
TI  - Mucinous cystadenoma of the ovary in perimenarchal girls.
AB  - Ovarian masses in children are an uncommon occurrence. They represent less than
      2% of all tumours in girls less than 16 years of age. Mucinous tumours of the
      ovary occur principally in middle adult life and are extremely rare prior to
      menarche. To the best of our knowledge, there are only 13 previous cases of
      benign mucinous cystadenoma (MCA) of the ovary in perimenarchal girls reported in
      the literature. We present six cases of this rare tumour. We reviewed the charts
      of six patients who presented with large MCA of the ovary. The patient's ages
      ranged from 13 to 14 years (mean 13.6 years). Two were premenarchal and four were
      within 1 year of menarche. All children presented with marked abdominal
      distension and discomfort. Except for one child who had ultrasound scan alone,
      all the others had either CT or MRI scan as well. Ultrasound demonstrated a large
      multiloculated cystic mass arising from the pelvis reaching the level of the
      xiphoid. CT demonstrated an enormous mass occupying almost the entire abdomen.
      The mass was partly solid, partly cystic and the cystic elements were
      multiloculated in all patients. Three patients demonstrated contralateral
      hydronephrosis on imaging. Laparotomy revealed a tumour arising from the left
      ovary in five patients and from the right ovary in one. Several litres of fluid
      were aspirated in order to deliver the tumour from the abdomen. All patients
      underwent oophorectomy or salpingo-oophorectomy. Histology revealed benign MCA of
      the ovary in all cases. On follow up, ranging from 2.4 to 5 years, all patients
      were well with no evidence of recurrence. MCA in perimenarchal girls usually
      affects the left ovary. Although this tumour is rare, this diagnosis should be
      considered in 11 to 15-year-old girls presenting with a very large abdominal
      mass.

PMID- 16416282
TI  - Catheterless and drainless open suprapubic cystolithotomy in children: a safe
      procedure.
AB  - The objective of this study is to compare the outcome of the children with
      vesical stones undergoing conventional open suprapubic cystolithotomy with those
      undergoing catheterless and drainless suprapubic cystolithotomy. The study
      included 176 children aged 1-15 years with bladder stones. It was a prospective
      study stretching over 14 years (1991-2003). In the initial years (1991-1994), 40
      patients were used to put a urethral catheter for 5 days and retropubic drain for
      48 h post-operatively, as has been recommended conventionally. From 1995 onwards
      we resorted to a catheterless-drainless (no suprapubic drain) suprapubic
      cystolithotomy in children with bladder stones. In all the patients, two-layered
      closure of bladder with absorbable sutures was done. The results of both
      protocols with regards to duration of hospitilisation and complications were
      compared. We observed that if the bladder is closed meticulously in two layers
      and complete haemostasis is achieved, bladder drainage by means of a catheter and
      drainage of retropubic space is not required. This approach allowed an early post
      operative recovery without increasing the risks of complications. However, the
      catheterisation was required for patients with infected urine, recurrent stones
      and those operated earlier for ano-rectal malformations. The authors feel that
      for vesical stones, the catheterless-drainless suprapubic cystolithotomy in
      children is a safe procedure barring a few above-stated situations. The
      advantages of this procedure are a shorter hospital stay, early mobility and
      decreased morbidity.

PMID- 16416283
TI  - Combined CYP1A1/GSTM1 at-risk genotypes are overrepresented in squamous cell lung
      carcinoma patients but underrepresented in elderly tumor-free subjects.
AB  - PURPOSE: Polycyclic aromatic hydrocarbons are activated by cytochrome P450 1A1
      (CYP1A1) and inactivated by glutathione S-transferase mu (GSTM1). Therefore, it
      is expected that a combination of proficient CYP1A1 genotype with deficient GSTM1
      variant would result in particularly elevated lung cancer (LC) risk, especially
      for squamous cell carcinoma (SCC). This study was aimed to validate whether the
      CYP1A1-C (3801) (CYP1A1*2) allele has an unfavorable significance alone and/or in
      combination with the GSTM1 deficiency. METHODS: We compared the distribution of
      CYP1A1 and GSTM1 genotypes in LC patients (n=141), healthy donors (HD, n=204),
      and elderly tumor-free smokers and non-smokers (ED, n=246). RESULTS: CYP1A1*2
      allele carriers demonstrated a clear-cut association with SCC: the adjusted odds
      ratios (OR) were 2.22 (95% CI=1.06-4.63) and 2.27 (95% CI=1.14-4.52) when HD and
      ED were used as referents, respectively. CYP1A1*2(+)/GSTM1(-) combined genotypes
      were overrepresented in the SCC patients (14/70, 20.0%) and underrepresented in
      the ED (19/246, 7.7%) as compared to the intermediate prevalence in the HD
      (26/204, 12.7%); the adjusted OR for SCC versus ED reached 3.85 (95% CI=1.43
      10.33). CONCLUSIONS: In agreement with some literature data, our results support
      the concerted role of CYP1A1 and GSTM1 at-risk genotypes in SCC predisposition.

PMID- 16416285
TI  - Influence of cyclic hydrostatic pressure on fibrocartilaginous metaplasia of
      achilles tendon fibroblasts.
AB  - The goal of this study was to demonstrate whether cyclically imposed hydrostatic
      pressure, compressive in nature, could induce fibrocartilaginous metaplasia in a
      purely tendinous cell source in vitro. The effect of short-duration cyclic
      hydrostatic pressure on tendon fibroblasts (tenocytes) expanded from rat Achilles
      tendon was studied. Total RNA was isolated either immediately after loading or 24
      h later. The mRNA expression of tendon and cartilage specific markers - Collagen
      types I and II, Sox9, and Aggrecan was quantified by real-time reverse
      transcription polymerase chain reaction over multiple biological samples (n=6).
      For immediately isolated RNA samples, there were statistically significant
      increases in mRNA expression of Aggrecan and Collagen type II, while Collagen
      type I significantly decreased. Noticeably, for RNA samples isolated 24 h later,
      there were further increases in mRNA expression of Aggrecan and Collagen type II,
      whereas Collagen type I increased roughly three-fold relative to the non-loaded
      control. These findings support the hypothesis that cyclic hydrostatic
      pressurization can induce fibrocartilaginous metaplasia in tenocytes by
      upregulation of cartilaginous gene expression. Also, it was demonstrated that
      changes in mRNA expression as a result of single 2 h pressurization persist even
      up to 24 h.

PMID- 16416284
TI  - Long-term refractive and visual outcome after penetrating keratoplasty only
      versus the triple procedure in Fuchs' dystrophy.
AB  - BACKGROUND: Long-term refractive and visual outcome after penetrating
      keratoplasty (PK) only and the triple procedure in eyes with Fuchs' endothelial
      dystrophy were assessed and compared. DESIGN: Retrospective, non-randomized,
      cross-sectional, clinical, single-centre study. METHODS: Ninety-two eyes of 87
      patients were divided into two groups. Group 1 consisted of 28 eyes (mean age
      62+/-13 years) that had undergone PK only and group 2 consisted of 64 eyes (mean
      age 69+/-10 years) that had undergone the triple procedure. Inclusion criteria
      were: (1) Fuchs' dystrophy, (2) central nonmechanical trephination, (3) double
      running suturing technique and (4) availability of 'two-sutures-out' findings. In
      all eyes, a central trephination was performed (donor trephination from the
      epithelial side) using the 193-nm excimer laser along metal masks with eight
      'orientation teeth/notches'. A double-running 10-0 nylon suture was applied in
      all eyes. Subjective refractometry (trial glasses), standard keratometry (Zeiss)
      and corneal topography analysis (TMS-1, Tomey) were performed in all eyes with
      'two-sutures-in', 'one-suture-out', and 'two-sutures-out'. Main outcome measures
      included refractive cylinder, keratometric and topographic net astigmatism,
      keratometric and topographic central power, best-corrected visual acuity (BCVA),
      spherical equivalent (SE) of manifest refraction, surface regularity index (SRI),
      surface asymmetry index (SAI), and regularity of keratometry mires. RESULTS: The
      results were compared between the two groups (i.e. group 1 vs group 2) at various
      stages (i.e. 'two-sutures-in', 'one-suture-out', 'two-sutures-out'). Refractive
      cylinder in dioptres [D] was 2.5/2.0/2.5 vs 2.0/1.5/3.0, keratometric astigmatism
      [D] was 3.5/2.6/3.0 vs 3.5/3.1/3.5 and topographic astigmatism [D] was
      3.9/4.1/4.9 vs 4.2/5.0/5.1. Keratometric central power [D] was 41.7/42.4/43.8 vs
      41.5/41.9/43.3 and topographic central power [D] was 42.3/43.6/43.7 vs
      42.6/41.8/44.3. BCVA was 0.5/0.6/0.6 vs 0.5/0.5/0.5. SE [D] was 0.0 /0.0/-0.5 vs 
      0.5/-0.5/-1.1. SRI was 1.5/1.1/1.0 vs 1.4/1.4/1.2 and SAI was 1.0/0.8/1.0 vs
      1.3/1.2/1.0. The proportion of 'regular' and 'mildly irregular' keratometry mires
      was 44% / 69% / 68% vs 29% / 46% / 66%. The differences between the two groups
      did not reach statistical significance at any of the stages. CONCLUSIONS:
      Refractive and visual outcome after the triple procedure did not differ
      significantly from that after PK only. Therefore, we recommend the triple
      procedure in elderly patients with Fuchs' dystrophy and cataract to avoid delayed
      visual rehabilitation and a second surgical procedure.

PMID- 16416286
TI  - Accurate quantification of PAHs in water in the presence of dissolved humic acids
      using isotope dilution mass spectrometry.
AB  - The effect of dissolved humic acids on the recovery of PAHs from water samples
      has been investigated using a commercially available humic acid preparation as
      colloid model and a mixture containing the 16 EPA PAHs. The presence of humic
      acid reduced the extraction efficiency down to between 10 and 75%. An analytical
      protocol was therefore developed for the accurate determination of PAHs in the
      presence of humic acids based on isotope dilution mass spectrometry. The
      procedure compensates for losses due to sorption of PAHs and can be used for the
      determination of the total PAH concentration in water, i.e. dissolved PAHs plus
      PAHs adsorbed on colloids. To obtain reliable estimates it is essential to allow
      a certain time for equilibration between the isotope spike and the aqueous matrix
      which may vary between 5 and 24 h, in correlation with the water solubility of
      PAHs. The protocol allows one to recover the 16 PAHs studied at 94 to 105%. The
      expanded uncertainty of the measurements was 5-7% for all PAHs. Liquid-liquid
      extraction and solid-phase extraction in combination with the developed isotope
      dilution protocol performed equally well for the quantification of PAHs from
      water samples rich in colloidal material.

PMID- 16416287
TI  - Effects of three simultaneous demands on glucose transport, resting metabolism
      and morphology of laboratory mice.
AB  - In nature, animals must successfully respond to many simultaneous demands from
      their environment in order to survive and reproduce. We examined physiological
      and morphological responses of mice given three demands: intestinal parasite
      infection with Heligmosomoides polygyrus followed by caloric restriction (70% of
      ad libitum food intake versus ad libitum for 10 days) and/or cold exposure (5
      degrees C vs. 23 degrees C for 10 days). We found significant interactions
      between these demands as well as independent effects. Small intestine structure
      and function changed with demands in both independent and interactive ways. Body
      mass decreased during caloric restriction and this decrease was greater for cold
      exposed than warm-exposed mice. In ad libitum fed mice, body mass did not change
      with either cold exposure or parasite infection but body composition (fat versus
      lean mass of whole body or organs) changed with both demands. Generally, organ
      masses decreased with caloric restriction (even after accounting for body mass
      effects) and increased with cold exposure and parasite infection whereas fat mass
      decreased with both caloric restriction and parasite infection. Mass adjusted
      resting metabolic rate (RMR) increased with cold exposure, decreased with caloric
      restriction but, unlike previous studies with laboratory mice, did not change
      with parasite infection. Our results demonstrate that the ability of mice to
      respond to a demand is influenced by other concurrent demands and that mice show
      phenotypic plasticity of morphological and physiological features ranging from
      the tissue level to the level of the whole organism when given three simultaneous
      demands.

PMID- 16416288
TI  - Evaluation of peripheral blood neutrophil leucocytes in lead-exposed workers.
AB  - BACKGROUND: Inorganic lead can interfere with humoral and especially cell
      mediated immunity even at frequently occurring (<50 microg/dl) blood lead (Pb-B)
      levels. Occupational exposure to lead causes a primary impairment of the
      chemotactic and phagocytic activities of neutrophil leucocytes. OBJECTIVE: To
      verify whether, after taking into account the main confounding factors,
      occupational lead exposure is shown to induce changes in the number of blood
      neutrophil leucocytes, and to assess a possible dose-response relationship
      between Pb-B and the circulating neutrophil count in exposed workers. SUBJECTS
      AND METHODS: The study included 68 male lead-exposed (E) workers and 59 male
      workers in a food plant, recruited as controls (NE). A standardized questionnaire
      probing work, social, familial and personal medical history was administered to
      all the subjects. Blood and urine samples were collected to determine the dose
      and effect biological indices of lead and the total white blood cell and
      neutrophil counts. RESULTS: Pb-B levels were significantly higher in E (geometric
      mean (GM): 20.5 microg/dl; 3.2-120 microg/dl) than in NE workers (GM: 3.5
      microg/dl; 1-11 microg/dl). The mean absolute neutrophil count (ANC) was
      significantly higher in E workers with respect to NE workers. ANC correlated
      significantly with the biological lead dose and effect indices. Moreover, there
      was a dose-dependent increase of ANC with increasing Pb-B levels. The linear
      relationship between ANC and Pb-B was confirmed even after correction for age,
      body mass index and smoking habit. We also found an interaction between Pb-B
      level and smoking habit in increasing the number of blood neutrophils in lead
      exposed workers. CONCLUSION: Our study is the first to describe a dose-dependent
      effect of lead on ANC in exposed workers. Our results underline the importance of
      promoting a further reduction of occupational lead exposure levels, adopting
      adequate individual protection means, as well as conducting medical campaigns
      against smoking, at the workplace.

PMID- 16416289
TI  - Cryptosporidium parvum bovine genotype oocysts in the respiratory samples of an
      AIDS patient: efficacy of treatment with a combination of azithromycin and
      paromomycin.
AB  - Cryptosporidium has been recognized as an emerging zoonotic agent of intestinal
      cryptosporidiosis leading to diarrhea, malabsorption syndrome, and weight loss in
      AIDS patients. In the present case, oocysts of zoonotic Cryptosporidium parvum
      were detected in the sputum and stool samples of an AIDS patient with a 3-month
      history of intestinal cryptosporidiosis. The oocysts were detected by modified
      Ziehl-Neelsen staining; confirmation was achieved by nested polymerase chain
      reaction (PCR), targeting the most polymorphic region of the 18S rRNA gene.
      Genotyping was done by restriction endonuclease digestion of the PCR product. The
      zoonotic C. parvum bovine genotype was identified in both intestinal and
      respiratory samples. Treatment with both azithromycin and paromomycin resulted in
      improvement of both intestinal and respiratory symptoms, as well as the
      elimination of the parasite. This is the first report of the identification of
      Cryptosporidium sp. oocysts in the respiratory samples obtained from an AIDS
      patient in Iran. Pulmonary cryptosporidiosis should be considered whenever an
      AIDS patient with intestinal cryptosporidiosis develops respiratory symptoms.

PMID- 16416290
TI  - Fine structure and cytochemical analysis of the intestinal wall along the body of
      adult female of Litomosoides chagasfilhoi (Nematoda: Filarioidea).
AB  - Litomosoides chagasfilhoi is a filariid nematode parasite of the abdominal cavity
      of the wild rodent Akodon cursor (Winge, 1887), that has been described and used
      in Brazil as a new model for human filariasis. The fine structure of the
      intestine of this nematode was analyzed based on observations made by light and
      transmission electron microscopies of serial sections along the body.
      Cytochemical analysis was carried out to investigate the composition of the
      intestinal wall. This structure consisted of a basal lamina and an epithelium of
      variable thickness, composed of cells that have an irregular shape. The cytoplasm
      of intestinal cells contains few organelles: vacuoles, lysosomal bodies, spheroid
      bodies, endoplasmic reticulum, and many large lipid droplets. In the anterior
      portion of the intestine, the lysosomal bodies, spheroid bodies, and vacuoles
      presented positive reaction for acid phosphatase, and carbohydrates were detected
      in lysosomal bodies. The midbody and posterior regions presented less organelles
      and lipid droplets, and nuclei were more abundant. Residues of L-fucose were
      detected by Ulex europaeus lectin binding in the midbody sections. Basic proteins
      were associated to lipid droplets, in the posterior region. In the whole
      extension of the intestine, carbohydrates were detected on tight junctions. These
      results indicate that the metabolized material in the epithelium can contribute
      to the microfilariae development and also probably can be involved with the
      excretory/secretory mechanism of these nematodes.

PMID- 16416291
TI  - Humoral response of chicken infected with the microsporidium Encephalitozoon
      hellem.
AB  - Chicken (Gallus gallus) were used as the experimental model for study of immune
      response against the microsporidium Encephalitozoon hellem (Didier et al., J Inf
      Dis 163:617-621, 1991) infection in birds. Two-day-old chicken were infected
      perorally or intraperitoneally with a dose of 10(7) spores of E. hellem. The anti
      E. hellem immunoglobulin (Ig)A, IgY, and IgM antibody responses in sera and
      dropping sample extracts were determined by enzyme-linked immunosorbent assay.
      Results have shown specific antibody production in sera and intestinal secretions
      of infected birds. Chicken inoculated perorally developed the lowest antibody
      response. Microsporidian spores were not identified in the smears from cloacal
      swab samples of individual chicken. Intestinal segment cultures of perorally
      infected chicken cultivated in vitro showed the highest production of specific
      IgY and IgA antibodies in jejunum segments. In the further course of infection,
      the colon produced the highest amount of IgA, and the ileum and colon produced
      the highest amount of IgY.

PMID- 16416292
TI  - Standardization of a very specific and sensitive single PCR for detection of
      Plasmodium vivax in low parasitized individuals and its usefulness for screening
      blood donors.
AB  - Here, we describe the standardization of a very sensitive and specific single
      Plasmodium vivax polymerase chain reaction (PCR) and its usefulness for diagnosis
      and screening procedures when a Plasmodium falciparum PCR was also utilized. The
      P. vivax PCR sensitivity threshold was 0.019 parasites per microliter, and a PCR
      fragment was only detected when P. vivax DNA was present. Among the 11 febrile
      patients with negative parasitological examination that attended the malaria
      service of Fundacao de Medicina Tropical do Amazonas, we diagnosed one P. vivax
      malaria by PCR. Among the 286 individuals considered suitable for blood donation,
      we also detected by PCR an individual with P. vivax malaria, and conversely, we
      did not detect any malaria infection in blood donor candidates considered
      unsuitable due to its past malaria history. We conclude that PCR is the method of
      choice for low-parasitized individuals and could therefore represent a
      complementary tool to safely rescue blood donor candidates considered unsuitable
      on the basis of malaria history.

PMID- 16416293
TI  - Effect of rSAG-1(P30) immunisation on the circulating and tissue parasites in
      guinea pigs as determined by quantitative PCR.
AB  - The efficacy of immunisation with Toxoplasma gondii recombinant protein (rSAG-1)
      was evaluated in the guinea pig model. For the infectious challenge, two strains,
      namely, strain C56 (10,000 tachyzoites) and strain 76K (100 cysts), were used to
      infect a group of 32 guinea pigs each. The circulating, cerebral and pulmonary
      parasite loads were determined with the real-time polymerase chain reaction (PCR)
      after immunisation. With the C56 strain, immunisation showed high activity with a
      reduction of greater than 1 log of the circulating and tissue parasite loads.
      Thus, there was a significantly lower circulating parasite load in the rSAG-1 +
      adjuvant group (0.5+/-1.5 Eq parasites/ml) as compared to that in the control
      group (67+/-110 Eq parasites/ml; p<0.05). In the same manner, the cerebral
      parasite load was much lower in the rSAG-1 + adjuvant group (10+/-20 Eq
      parasites/g) than that in the control group (339+/-291 Eq parasites/g; p<0.01).
      On the other hand, with the 76K strain, the effect of immunisation was much less
      and that only on the pulmonary parasite load [p(lung)<0.05]. This could be due to
      the use of different strains and stages of the parasite and/or the difference in
      the route of administration for challenge. The quantitative PCR technique used
      has shown a good correlation with animal inoculation, and when associated with
      the guinea pig model, it seems to be a useful and reproducible technique for
      future vaccine studies.

PMID- 16416294
TI  - Protective effect of egg-propagated Eimeria tenella (local isolates) gametocytes
      as vaccine(s) against mixed species of coccidia in chickens.
AB  - Egg propagated gametocytes of Eimeria tenella (local isolates) were used to
      prepare the adjuvanted (Amphigen) and nonadjuvanted vaccine(s) and evaluated on
      the basis of cellular, humoral, and challenge responses. Modified splenic cell
      migration inhibition test and enzyme-linked immunosorbant assay were used to
      assess the cellular and humoral responses, respectively. Chicken in groups A, B,
      C, and D were given adjuvanted vaccine (orally), adjuvanted vaccine
      (subcutaneously, s/c), nonadjuvanted vaccine (orally), and nonadjuvanted vaccine
      s/c, respectively. Control groups E, F, G, and H were given adjuvant (orally),
      adjuvant (s/c), phosphate-buffered saline (PBS) + adjuvant (orally), and PBS +
      adjuvant (s/c), respectively. On 5 and 15 days post vaccination after boosting,
      significantly higher (P<0.05) cell-mediated and humoral responses were detected
      in vaccinated chicken compared to control. No significant effect of adjuvant and
      vaccination route on the immune responses was found. Maximum percent protection
      (survivors after challenge) against mixed species of genus Eimeria was observed
      in group A (71.42%) followed by group C (63.63%), B (59.09%), and group D
      (54.54). Significantly higher (P<0.05) oocysts per gram (OPG) of droppings was
      observed in the control groups compared to the vaccinated chickens. Maximum
      percent reduction in OPG was also recorded in group A (86) followed by group C
      (84), group B (83), and group D (82). From these results, it was concluded that
      egg-propagated gametocytes (E. tenella) that gave protection upon challenge may
      be due to the control of E. tenella. Further studies on its feasibility as
      commercial vaccine are underway.

PMID- 16416295
TI  - Molecular cloning and characterization of cDNA encoding a novel cytosolic
      glutathione transferase from Clonorchis sinensis.
AB  - Glutathione transferases (GSTs) are a group of multifunction isoenzymes coded by
      many genes. A cDNA encoding a novel cytosolic GST enzyme was cloned from a
      Clonorchis sinensis (Cs) adult worm cDNA library by large-scale sequencing. This
      new cDNA contains 786 bp with a putative open reading frame of 212 amino acids.
      The deduced amino acid sequence exhibits 61% identity to C. sinensis cytosolic 28
      kDa GST. Recombinant CsGST was overexpressed in Escherichia coli BL21(DE3) and
      was purified by Ni-NTA Agarose. Enzymatic assays showed that the recombinant
      CsGST had a high activity of 22.7 U mg(-1). The average K (m) of the CsGST for 1
      chloro-2,4-dinitrobenzene is 111 microM. Cibacron blue F3GA and albendazole
      inhibited the CsGST activity with respective average IC(50) of 1.1 and 247.1
      microM. It provides a model for the structure and physiological function analysis
      on CsGST. The nucleotide sequence reported in this paper has been submitted to
      the GenBank Database with accession number DQ179264.

PMID- 16416296
TI  - Correlation of invasion and metastasis of cancer cells, and expression of the
      RAD21 gene in oral squamous cell carcinoma.
AB  - Although RAD21 is involved in the repair of double-strand breaks in DNA and is
      essential for mitotic growth, its role in cancer has been unclear. In this study,
      the relevance of RAD21 gene expression to the invasion and metastasis of oral
      squamous cell carcinoma was clarified using laser microdissection and real-time
      polymerase chain reaction (PCR). Using two different metastatic potential oral
      squamous cells [high-metastatic-potential squamous cell carcinoma cells (SAS-Ly)
      and low-metastatic-potential squamous cell carcinoma cells (SAS)], the relation
      of RAD21 gene expression to apoptosis, invasion, and metastasis was examined. The
      results showed that RAD21 gene expression was significantly decreased in oral
      squamous cell carcinoma when it expressed the INFbeta and INFgamma invasion
      patterns in comparison with the INFalpha invasion pattern (p<0.01). In addition,
      in comparison with SAS cells, SAS-Ly cells indicated tolerance to cell death
      induced by an apoptosis induction reagent, while the expression level of the
      RAD21 gene in SAS cells was increased by the apoptosis induction reagent.
      However, in SAS-Ly cells, the reagent induced no significant difference. Our
      findings indicate that the RAD21 gene was closely related to the invasion and
      metastasis of cancer cells.

PMID- 16416297
TI  - High-level heterologous production and functional expression of the sec-dependent
      enterocin P from Enterococcus faecium P13 in Lactococcus lactis.
AB  - Enterocin P (EntP), a sec-dependent bacteriocin from Enterococcus faecium P13,
      was produced by Lactococcus lactis. The EntP structural gene (entP) with or
      without the EntP immunity gene (entiP) was cloned in (1), plasmid pMG36c under
      control of the lactococcal constitutive promoter P32, (2) in plasmid pNG8048e
      under control of the inducible PnisA promoter, and (3) in the integration vector
      pINT29. Introduction of the recombinant vectors in L. lactis resulted in
      production of biologically active EntP in the supernatants of L. lactis subsp.
      lactis IL1403 and L. lactis subsp. cremoris NZ9000, and the coproduction of nisin
      A and EntP in L. lactis subsp. lactis DPC5598. The level of production of EntP,
      detected and quantified by specific anti-EntP antibodies and a noncompetitive
      indirect enzyme-linked immunosorbent assay, by the recombinant L. lactis strains
      depended on the host strain, the expression vector, and the presence of the entiP
      gene in the constructs of the recombinant L. lactis strains. The highest amount
      of EntP was produced with derivatives containing entP and entiP, for both L.
      lactis IL1403 and L. lactis NZ9000. These derivatives produced up to five- to six
      fold more EntP than E. faecium P13. Mass spectrometry analysis revealed that EntP
      purified from L. lactis IL1403 (pJP214) has a molecular mass identical to that
      purified from E. faecium P13, suggesting that the synthesis, processing, and
      secretion of EntP progresses efficiently in recombinant L. lactis hosts.

PMID- 16416298
TI  - [Prevention of microalbuminuria in type 2 diabetes. BENEDICT study].

PMID- 16416299
TI  - [Obesity in children and adolescents: current recommendations for prevention and
      treatment].
AB  - Overweight and obesity in children and adolescents represent significant health
      disorders, which until recently had received little attention. Germany's
      lifestyle has changed considerably since the 1980s. Children spend more time than
      ever in front of the television or computer and do not exercise enough. So-called
      children's food often contains too much fat and sugar. Overweight children turn
      into overweight adults with a high risk of developing type 2 diabetes mellitus,
      cardiovascular and orthopedic disorders as well as other diseases. Therapeutic
      behavioral interventions only meet with medium-term success in a minority of
      highly motivated families. The sole solution to this increasing problem appears
      to lie in primary prevention. Appropriate measures cannot, however, be introduced
      into the healthcare system by individual persons or groups alone. Concerted
      cooperation between those involved in politics, science, and healthcare is needed
      to support the goal of changing those living conditions that influence the
      nutritional and exercise behavior of children in our country.

PMID- 16416301
TI  - [20-year old woman with diarrhea of unknown etiology].
AB  - We report on a 20-year old woman who suffered from watery diarrhea. The results
      of the histology and the serology as well as clinical symptoms lead us to the
      diagnosis of sprue. Under specific gluten-free diet the diarrhea frequency was
      reduced. After a few weeks the patient returned to hospital again because of
      watery diarrhea. Histological examination of duodenal biopsy specimen showed a
      protracted infectious duodenitis and a secondary villous flattening of the small
      bowel. This diagnosis was a life-threatening illness that needed antibiotic
      treatment. These patients receive parenteral nutrition as long as the villous
      have not been recovered from the flattening. Additionally octreotid can be given
      to reduce the frequency of the diarrhea.

PMID- 16416300
TI  - [Evidence based therapy of obesity].
AB  - For medical reasons, subjects with a BMI > or =30 kg/m(2) or a BMI > or =25
      kg/m(2) and comorbidities such as type 2 diabetes mellitus should be considered
      for participation in a weight loss program. At present, there is a broad spectrum
      of measures to reduce body weight which have been validated in randomized
      controlled trials. The primary target of all intervention programs is to change
      lifestyle in order to establish an adequate calorie intake and an increase in
      physical activity. Other more aggressive options to escalate the efforts for
      reducing body weight include very low calorie diets, weight-lowering drugs and
      for the extreme forms of obesity surgical techniques. The treatment should be
      tailored to the "real world" and wishes of the individual patient. Patient
      empowerment is essential to achieve long-term self management of the weight
      problem. To effectively control the obesity epidemic it is of critical importance
      to establish preventive measures in the society. There is an urgent need to
      improve the structural prerequisites for a better treatment of people with
      overweight/obesity.

PMID- 16416302
TI  - Quantitative prediction of macrolide drug-drug interaction potential from in
      vitro studies using testosterone as the human cytochrome P4503A substrate.
AB  - OBJECTIVE: Macrolide antibiotics are mechanism-based inactivators of CYP3A
      enzymes that exhibit varying degrees of inhibitory potency. Our aim was to
      predict quantitatively the drug-drug interaction (DDI) potential of five
      macrolides from in vitro studies using testosterone as the CYP3A substrate, and
      to compare the predictions generated from human liver microsomal and recombinant
      CYP3A4 data. METHODS: The in vitro kinetic constants of CYP3A inactivation (K (I)
      and k (inact)) were estimated by varying the time of pre-incubation and the
      concentration of troleandomycin, erythromycin, clarithromycin, roxithromycin or
      azithromycin. CYP3A activity was determined from the measurement of testosterone
      6beta-hydroxylation with human liver microsomes (HLM) and recombinant CYP3A4 as
      the enzyme sources. The mechanism-based pharmacokinetic model was fitted with
      inactivation data to predict the increase in oral area under the plasma
      concentration-time curve (AUC) for midazolam. RESULTS: All five macrolides
      inactivated testosterone 6beta-hydroxylation by HLM and recombinant CYP3A4 with k
      (inact) values in the range of 0.023 to 0.058 min(-1). The potency of
      inactivation (K (I)) was higher using recombinant CYP3A4 as the enzyme source.
      The oral AUCs for midazolam were predicted from HLM data to increase 16.6, 5.3,
      4.6, 1.6 and 1.2-fold due to the inhibition of metabolic clearance by
      troleandomycin, erythromycin, clarithromycin, roxithromycin and azithromycin,
      respectively. These results are within the range of the AUC ratios reported for
      clinical DDI studies. The predicted AUC increases generated using recombinant
      CYP3A4 overestimated the magnitude of the DDIs. CONCLUSIONS: The DDI potential of
      five macrolide antibiotics was quantitatively predicted from in vitro studies
      using testosterone as the CYP3A substrate with HLM as the enzyme source.

PMID- 16416304
TI  - Gastro-intestinal problems and concomitant medication in NSAID users: additional
      findings from a questionnaire-based survey in Italy.
AB  - BACKGROUND: In a previous questionnaire-based survey, we found extensive use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with risk factors for
      serious gastrointestinal complications. AIM: This study focused on the use of
      NSAIDs in subjects who reported either (a) pre-existing disorders which would
      have required caution in using NSAIDs (e.g. dyspepsia/heartburn or peptic ulcer)
      or (b) co-medication with drugs having a high risk of interacting with NSAIDs.
      METHODS: Between March and September 2002, 65 general practitioners (GPs)
      submitted a validated self-administered questionnaire on health status and drug
      use to 3,250 subjects (age >or=18 years, stratified by sex and age). The
      questionnaire was divided into three parts: (1) sociodemographic information, (2)
      symptoms/illnesses (in the previous 6 months) and (3) drugs taken during the
      previous week. RESULTS: Of the 2,738 subjects who filled in the questionnaire
      (84% of responders), 633 (23%) used NSAIDs and, among them, 114 (18%) were
      chronic users. Among the subjects reporting dyspepsia/heartburn or ulcer (n=909
      of 2,738), 24% were occasional NSAID users and 6% chronic users. Of the chronic
      NSAID users reporting gastrointestinal symptoms, 35% also used a drug for acid
      related disorders, but only 14% used daily a proton pump inhibitor (PPI). One
      hundred six subjects used concomitantly more than one NSAID. Eighteen percent of
      the subjects using corticosteroids also reported NSAID use; similar proportions
      were seen in subjects using selective serotonin reuptake inhibitor (SSRI)
      antidepressants or calcium channel blockers, whereas 6% of the subjects with oral
      anticoagulants used NSAIDs. CONCLUSIONS: Our study shows that NSAIDs are
      frequently used in patients with upper gastrointestinal complaints or in
      combination with potentially interacting medications. Adverse effects and
      untoward drug interactions should be monitored in patients treated with NSAIDs in
      order to minimise their occurrence.

PMID- 16416303
TI  - Influence of HCV or HBV coinfection on adverse drug reactions to antiretroviral
      drugs in HIV patients.
AB  - OBJECTIVE: To compare the profile of adverse drug reactions (ADRs) to
      antiretroviral (ARV) drugs in patients coinfected with hepatitis C virus (HCV) or
      hepatitis B virus (HBV) versus non-coinfected patients with human
      immunodeficiency virus (HIV) infection. METHODS: We used the French
      Pharmacovigilance Database from 2000 to 2002. Selected patients were classified
      into four groups: HIV+HCV, HIV+HBV, HIV+HBV+HCV and HIV patients. We compared
      patients' characteristics and profiles of ADRs to ARV drugs between the four
      groups. RESULTS: We identified 1,068 HIV, 172 HIV+HCV, 72 HIV+HBV and 26
      HIV+HBV+HCV patients with 2,398, 446, 183 and 70 ADRs related to ARV drugs,
      respectively. The "seriousness" of these ADRs was similar in HIV and coinfected
      patients but death related to the ADRs was more frequent in HIV+HCV (9.4%) than
      in HIV (3.6%) patients (p<0.001). "Liver and bile system disorders" were more
      frequently reported in HIV+HCV and HIV+HBV patients than in HIV patients (17.3%
      and 20.8%, respectively, versus 8.9%, p<0.001). In HIV+HBV patients, the
      occurrence of these ADRs was independently associated in a logistic regression
      model to male gender [odds ratio (OR): 9.28, 95% confidence interval (CI): 2.74
      31.36], exposure to zalcitabine (OR: 17.82, 95% CI: 1.49-212.95) or efavirenz
      (OR: 5, 95% CI: 1.44-17.33). "Red blood cell disorders" were also more frequent
      in HIV+HCV (7.4%) than in HIV (4.4%) patients (p<0.01). CONCLUSION: Hepatic or
      haematological (mainly anaemia) ADRs to ARV drugs are more frequent in coinfected
      patients than in HIV patients. This study underlines the importance of hepatitis
      B or C in the occurrence of ADRs in HIV patients on ARV drugs.

PMID- 16416305
TI  - Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam
      and quazepam.
AB  - OBJECTIVE: Grapefruit juice (GFJ) inhibits cytochrome P450 (CYP) 3A4 in the gut
      wall and increases blood concentrations of CYP3A4 substrates by the enhancement
      of oral bioavailability. The effects of GFJ on two benzodiazepine hypnotics,
      triazolam (metabolized by CYP3A4) and quazepam (metabolized by CYP3A4 and
      CYP2C9), were determined in this study. METHODS: The study consisted of four
      separate trials in which nine healthy subjects were administered 0.25 mg
      triazolam or 15 mg quazepam, with or without GFJ. Each trial was performed using
      an open, randomized, cross-over design with an interval of more than 2 weeks
      between trials. Blood samples were obtained during the 24-h period immediately
      following the administration of each dose. Pharmacodynamic effects were
      determined by the digit symbol substitution test (DSST) and utilizing a visual
      analog scale. RESULTS: GFJ increased the plasma concentrations of both triazolam
      and quazepam and of the active metabolite of quazepam, 2-oxoquazepam. The area
      under the curve (AUC)(0-24) of triazolam significantly increased by 96% (p<0.05).
      The AUC(0-24) of quazepam (+38%) and 2-oxoquazepam (+28%) also increased;
      however, these increases were not significantly different from those of
      triazolam. GFJ deteriorated the performance of the subjects in the DSST after the
      triazolam dose (-11 digits at 2 h after the dose, p<0.05), but not after the
      quazepam dose. Triazolam and quazepam produced similar sedative-like effects,
      none of which were enhanced by GFJ. CONCLUSION: These results suggest that the
      effects of GFJ on the pharmacodynamics of triazolam are greater than those on
      quazepam. These GFJ-related different effects are partly explained by the fact
      that triazolam is presystemically metabolized by CYP3A4, while quazepam is
      presystemically metabolized by CYP3A4 and CYP2C9.

PMID- 16416306
TI  - Immunocytochemical study of glycine receptors in the retina of the frog Xenopus
      laevis.
AB  - The expression of glycine receptors in the retina of clawed frog, Xenopus laevis
      was studied immunocytochemically. Glycine receptors (GlyRs), as revealed by means
      of several different antibodies, were mainly distributed in the inner (IPL) and
      the outer plexiform layers. Their composition was determined to include alpha2
      and alpha3 subunits. Typical punctate appearance and specific lamination in the
      IPL were seen with each of the antibodies directed against the different GlyRs'
      subunits. A notion for diversity of the glycine receptors was put forward,
      according to which the alpha2 and alpha3 subunits are located in different
      subtypes of glycine synapses.

PMID- 16416308
TI  - Heterogeneous occurrence of aquaporin-4 in the ependyma and in the
      circumventricular organs in rat and chicken.
AB  - Aquaporins are selective water channel proteins critical in volume homeostasis.
      In the CNS AQP4 predominates, localized mainly in the glia limitans, the
      perivascular endfeet and ependyma. The present immunofluorescent study reveals
      the distribution of aquaporin-4 in the circumventricular organs in rat and
      chicken brains. The ventricular ependyma (especially in the third one), the
      subfornical organ, the area postrema, the rat pineal body (in part), and the
      vascular organ of lamina terminalis were marked by intense immunopositivity.
      Several areas, however, proved to be immunonegative: the central canal, the
      subcommissural organ, the ependymal zone of the median eminence in rat but its
      whole thickness in chicken, the subtrochlear organ, and the paraventricular
      organ. The immunostaining of the lateral septal and subseptal organs were similar
      to their environment. Results on developing rats suggested that the aquaporin-4
      immunonegativity is a secondary phenomenon. Surveying other structural and
      functional features, no clear explanation of the heterogeneous occurrence of
      aquaporin-4 was found. The absence of aquaporin-4 seems to correlate with some
      features of the "ependymal organs" (thickened, pseudostratified ependyma,
      presence of blood-brain barrier) and with the avoidance of GFAP. On the other
      hand, the organs rich in aquaporin-4 have features of the "hypendymal organs"
      (glial and vascular plexus but no blood-brain barrier). There are organs,
      however, which do not fit into either group completely, i.e. the lateral septal
      and subseptal organs. Presence of tight junctions coincides with the absence of
      aquaporin-4 in the ependyma of spinal cord, the subcommissural organ and the
      ependyma of median eminence.

PMID- 16416307
TI  - Dual odontogenic origins develop at the early stage of rat maxillary incisor
      development.
AB  - Developmental process of rat maxillary incisor has been studied through
      histological analysis and investigation of tooth-related gene expression patterns
      at initial tooth development. The tooth-related genes studied here are fibroblast
      growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog
      (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone
      morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium
      and/or ectomesenchyme at the stage of epithelial thickening to the early bud
      stage of tooth development. Both the histological observation and tooth-related
      gene expression patterns during early stage of maxillary incisor development
      demonstrate that dual odontogenic origins aligned medio-laterally in the medial
      nasal process develop, subsequently only single functional maxillary incisor
      dental placode forms. The cascade of tooth-related gene expression patterns in
      rat maxillary incisor studied here is quite similar to those of the previous
      studies in mouse mandibular molar, even though the origins of oral epithelium and
      ectomesenchyme involved in development of maxillary incisor and mandibular molar
      are different. Thus, we conclude that maxillary incisor and mandibular molar
      share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4
      genes at the stage of oral epithelial thickening to the early bud stage of tooth
      development.

PMID- 16416309
TI  - [Methods of burn treatment. Part II: Technical aspects].
AB  - The best treatment for burns and scalds depends on the depth of the skin
      necrosis. Epidermal and superficial dermal burn injuries (IIa) can heal
      spontaneously with conservative treatment without scar development, but deep
      dermal or full-thickness burns constitute an absolute indication for surgery.
      Full-thickness or split-thickness skin grafts are used for wound closure. In the
      case of extensive burn injuries allografts are used for temporary wound closure.
      In certain licensed laboratories autologous keratinocytes can be cultured for
      transplantation. In circumferential burn injuries affecting the extremities or
      the trunk the rigid eschar has to be incised to relieve the pressure behind it.
      Following a debridement conservative treatment of superficial dermal burns
      involving wound coverage with biosynthetic dressings or nanocristalline silver
      gauze dressings or use of special disinfecting ointments can be implemented.

PMID- 16416310
TI  - Quantitative assessment of DNA methylation: Potential applications for disease
      diagnosis, classification, and prognosis in clinical settings.
AB  - Deregulation of the epigenome is now recognized as a major mechanism involved in
      the development and progression of human diseases such as cancer. As opposed to
      the irreversible nature of genetic events, which introduce changes in the primary
      DNA sequence, epigenetic modifications are reversible and leave the original DNA
      sequence intact. There is now evidence that the epigenetic landscape in humans
      undergoes modifications as the result of normal aging, with older individuals
      exhibiting higher levels of promoter hypermethylation compared to younger ones.
      Thus, it has been proposed that the higher incidence of certain disease in older
      individuals might be, in part, a consequence of an inherent change in the control
      and regulation of the epigenome. These observations are of remarkable clinical
      significance since the aberrant epigenetic changes characteristic of disease
      provide a unique platform for the development of new therapeutic approaches. In
      this review, we address the significance of DNA methylation changes that result
      or lead to disease, occur with aging, or may be the result of environmental
      exposure. We provide a detailed description of quantitative techniques currently
      available for the detection and analysis of DNA methylation and provide a
      comprehensive framework that may allow for the incorporation of protocols which
      include DNA methylation as a tool for disease diagnosis and classification, which
      could lead to the tailoring of therapeutic approaches designed to individual
      patient needs.

PMID- 16416312
TI  - Fibroblast migration after myocardial infarction is regulated by transient SPARC
      expression.
AB  - Secreted protein, acidic, and rich in cysteine (SPARC) is thought to regulate
      cell matrix interaction during wound repair. We hypothesized that SPARC might
      promote migration via integrin-dependent mechanisms. The present study was
      designed to clarify the contribution of SPARC in the wound healing process after
      myocardial infarction (MI). Adult mice received a specific alpha(v) integrin
      inhibitor or vehicle through osmotic mini pumps. Mice of each group were either
      sham-operated or MI was induced. SPARC expression was investigated 2 days, 7
      days, and 1 month after the surgical procedure. For migration assays, a modified
      Boyden chamber assay was used. A transient increase of SPARC levels was observed,
      starting at day 2 (2.55+/-0.21), day 7 (3.72+/-0.28), and 1 month (1.9+/-0.16)
      after MI. After 2 months, SPARC expression dropped back to normal levels compared
      to sham-operated hearts. Immunofluorescence analysis showed an increase of SPARC
      in the infarcted area 2 days after MI, a strong increase in the scar area 7 days
      after MI, and only low levels in the scar area 2 months after MI. Integrin
      alpha(v) inhibition abolished the up-regulation of SPARC. In vitro migration
      assays demonstrated that fibronectin-stimulated haptotaxis of fibroblasts was
      modulated by SPARC. This study provides evidence that SPARC is significantly up
      regulated in the infarcted region after MI. This up-regulation is dependent on
      alpha(v) integrins. As SPARC is found to regulate fibroblast migration, it
      appears to play an important role in the injured myocardium with regard to
      healing and scar formation.

PMID- 16416313
TI  - Variation in the lipoprotein lipase gene influences exercise-induced left
      ventricular growth.
AB  - The adult heart relies predominantly on fatty acids (FA) for energy generation,
      and defects in FA catabolism cause dramatic left ventricular (LV) growth in early
      age. Since lipoprotein lipase (LPL) is the key enzyme in plasma triglyceride
      catabolism and is highly expressed in the myocardium, we investigated an
      association between the functional LPL gene serine 447 stop (S447X) variant and
      exercise-induced LV growth. The S447X variant was genotyped in 146 British Army
      recruits undergoing a 10-week exercise programme. Over the training period, X447
      allele carriers showed less LV growth than S447 homozygotes (SS, 5.8+/-0.7%; SX,
      2.2+/-1.5%; P=0.03) and a decrease in systolic blood pressure (DeltaSBP: SS,
      1.9+/-1.3 mmHg; SX, -5.7+/-2.2 mmHg; P=0.015). Although LPL genotype did not
      significantly predict LV growth with DeltaSBP in statistical modelling (LPL,
      P=0.14; DeltaSBP, P=0.06), regression analysis indicated that LPL S447X genotype
      effect on DeltaSBP accounted for only 20% of the effect on LV growth. In
      multivariate analysis, LPL, peroxisome-proliferator-activated receptor alpha and
      angiotensin-converting enzyme genotypes were independent predictors of cardiac
      growth. Thus, LPL S447X genotype influenced exercise-induced changes in LV mass
      and SBP. Change in blood pressure accounted for a proportion of LV growth. These
      data suggest that increased myocardial FA availability may reduce exercise
      induced LV growth.

PMID- 16416314
TI  - Lipoprotein lipase and heart size.

PMID- 16416315
TI  - Tetranucleotide repeats in coding regions: no evidence for involvement in EMAST
      carcinogenesis.
AB  - Genetic instability is a hallmark of malignancy. In the majority of malignant
      tumors, chromosomal instability leads to major numerical and structural
      chromosomal aberrations. In contrast, some tumors have a deficient DNA mismatch
      repair system and accumulate mutations particularly in repetitive mono- and
      dinucleotide sequences, a phenomenon referred to as microsatellite instability
      (MSI). Recently, a novel phenotype of tumors presenting with elevated
      microsatellite alterations at selected tetranucleotide repeats (EMAST) has been
      reported. To date, not much is known about the molecular mechanisms of EMAST
      tumorigenesis. In MSI tumors, instability at specific mono- and dinucleotide
      repeats leads to alteration of genes carrying these repeats and thus may
      contribute to MSI tumorigenesis. We hypothesized that, similarly to the MSI
      phenotype, development of EMAST cancers may be promoted by mutations affecting
      tetranucleotides located in coding regions of the genome. To test this
      hypothesis, we performed a genome-wide database search to identify
      tetranucleotides in gene-encoding regions. Only seven tetranucleotide repeats
      located in predicted gene-encoding regions were retrieved. Allele length analysis
      yielded three remaining candidates with a monomorphic pattern in healthy
      individuals. Mutation analysis revealed that none of these three candidates
      displayed mutations in EMAST-positive bladder cancers. These data suggest that
      mutational inactivation of tetranucleotide-containing genes is very unlikely to
      contribute to the progression of EMAST tumors.

PMID- 16416311
TI  - The sarcomeric Z-disc: a nodal point in signalling and disease.
AB  - The perception of the Z-disc in striated muscle has undergone significant changes
      in the past decade. Traditionally, the Z-disc has been viewed as a passive
      constituent of the sarcomere, which is important only for the cross-linking of
      thin filaments and transmission of force generated by the myofilaments. The
      recent discovery of multiple novel molecular components, however, has shed light
      on an emerging role for the Z-disc in signal transduction in both cardiac and
      skeletal muscles. Strikingly, mutations in several Z-disc proteins have been
      shown to cause cardiomyopathies and/or muscular dystrophies. In addition, the
      elusive cardiac stretch receptor appears to localize to the Z-disc. Various
      signalling molecules have been shown to interact with Z-disc proteins, several of
      which shuttle between the Z-disc and other cellular compartments such as the
      nucleus, underlining the dynamic nature of Z-disc-dependent signalling. In this
      review, we provide a systematic view on the currently known Z-disc components and
      the functional significance of the Z-disc as an interface between biomechanical
      sensing and signalling in cardiac and skeletal muscle functions and diseases.

PMID- 16416316
TI  - Regulation of ethylene levels in canola (Brassica campestris) by 1
      aminocyclopropane-1-carboxylate deaminase-containing Methylobacterium
      fujisawaense.
AB  - We report the presence of ACC deaminase in Methylobacterium fujisawaense and its
      lowering of ethylene levels and promotion of root elongation in canola seedlings
      under gnotobiotic conditions. To test a part of the previous model proposed for
      ACC deaminase producing bacteria with Methylobacterium, ACC levels and various
      enzyme activities were monitored in canola. Lower amounts of ACC were present in
      the tissues of seeds treated with M. fujisawaense strains than in control seeds
      treated with MgSO(4). Though the increased activities of ACC synthase in the
      tissue extracts of the treated seedlings might be due to bacterial indole-3
      acetic acid, the amount of ACC was reduced due to bacterial ACC deaminase
      activity. The activities of ACC oxidase, the enzyme catalyzing conversion of ACC
      to ethylene remained lower in M. fujisawaense treated seedlings. This
      consequently lowered the ethylene in plants and prevented ethylene inhibition of
      root elongation. Our results collectively suggest that Methylobacterium commonly
      found in soils, as well as on the surfaces of leaves, seeds, and in the
      rhizosphere of a wide variety of plants could be better exploited to promote
      plant growth.

PMID- 16416317
TI  - Function of mitochondria during the transition of barley protoplasts from low
      light to high light.
AB  - Mitochondrial contribution to photosynthetic metabolism during the transition
      from low light (25-100 micromol quanta m(-2) s(-1), limiting photosynthesis) to
      high light (500 micromol quanta m(-2) s(-1), saturating photosynthesis) was
      investigated in protoplasts from barley (Hordeum vulgare) leaves. After the light
      shift, photosynthetic oxygen evolution rate increased rapidly during the first 30
      40 s and then declined up to 60-70 s after which the rate increased to a new
      steady-state after 80-110 s. Rapid fractionation of protoplasts was used to
      follow changes in sub-cellular distribution of key metabolites during the light
      shift and the activation state of chloroplastic NADP-dependent malate
      dehydrogenase (EC 1.1.1.82) was measured. Although oligomycin (an inhibitor of
      the mitochondrial ATP synthase) affected the metabolite content of protoplasts
      following the light shift, the first oxygen burst was not affected. However, the
      transition to the new steady-state was delayed. Rotenone (an inhibitor of
      mitochondrial complex I) had similar, but less pronounced effect as oligomycin.
      From the analysis of metabolite content and sub-cellular distribution we suggest
      that the decrease in oxygen evolution following the first oxygen burst is due to
      phosphate limitation in the chloroplast stroma. For the recovery the control
      protoplasts can utilize ATP supplied by mitochondrial oxidative phosphorylation
      to quickly overcome the limitation in stromal phosphate and to increase the
      content of Calvin cycle metabolites. The oligomycin-treated protoplasts were
      deficient in cytosolic ATP and thereby unable to support Calvin cycle operation.
      This resulted in a delayed capacity to adjust to a sudden increase in light
      intensity.

PMID- 16416318
TI  - Cardiac vagal outflow after aerobic training by analysis of high-frequency
      oscillation of the R-R interval.
AB  - This study was designed to assess the effect of aerobic training on the dynamics
      between the R-R interval length and the high-frequency (HF) oscillation of the R
      R interval. Seventeen healthy males (26+/-2 years) participated in an 8-week
      aerobic training intervention. The mean HF spectral power (0.15-0.4 Hz) of the R
      R interval and the mean R-R interval length were analyzed from 24-h recordings.
      HF power was also analyzed in 5-min sequences and plotted as a function of the
      corresponding mean R-R interval length. The relationship between the R-R interval
      length and the HF power was analyzed by a quadratic regression model. The
      relationship was defined as saturated if the distinct deflection point of the
      model occurred before the maximum R-R interval. Otherwise, the relationship was
      defined as linear. Additionally, the mean HF power was calculated from the linear
      portion of the R-R interval versus the HF power regression curve (HF index).
      Before the training intervention, seven subjects had a saturated HF power. After
      the intervention, five new cases of saturated HF power were observed. The mean HF
      power of the 24-h recording did not change in the group with a saturated HF power
      before training (7.4+/-0.8 vs. 7.6+/-0.8 ms(2)), but the HF index increased
      (6.7+/-0.7 vs. 7.1+/-0.7 ms(2), P<0.05). We conclude that enhanced vagal activity
      due to aerobic training increases the prevalence of the saturation of the HF
      oscillation of the R-R interval variability in healthy subjects. HF power
      calculated from unsaturated area detects more accurately subtle changes in the
      vagally mediated beat-to-beat variability of the R-R interval after aerobic
      training than the mean 24-h HF power.

PMID- 16416319
TI  - Maximal force during eccentric and isometric actions at different elbow angles.
AB  - The purpose of this study was to examine a course of force potentiation and/or
      inhibition during maximal voluntary eccentric action. Maximal voluntary force
      (MVC) of elbow flexion of ten healthy male volunteers was measured during
      isometric and isokinetic eccentric action starting from 80 degrees or 110 degrees
      and ending at 140 degrees elbow angle. Surface EMG was recorded from biceps
      brachii (BB) and brachioradialis (BR) muscles. Maximal voluntary eccentric force
      during the first 10 degrees of the movement was higher (P<0.001) than the maximal
      voluntary isometric preactivation force both in 80 degrees and in 110 degrees
      starting position at all three velocities (1, 2, and 4 rad s(-1)). The relative
      force potentiation was velocity dependent being smallest at the lowest stretching
      speed (P<0.01). Average EMG (aEMG) of BB and BR decreased as the joint angle
      increased both in eccentric and in isometric actions but the decrease in aEMG
      towards extension was somewhat higher in eccentric actions as compared to
      isometric. It was concluded that the force measured during the first 10 degrees
      of eccentric contraction always exceeded the maximal voluntary isometric
      preactivation force regardless of the joint angle or of the movement velocity.
      When maximal voluntary preactivation preceded the stretch, the relative force
      potentiation seemed to be greater at higher stretching velocities (velocity
      dependent) while at lower preactivation levels, the velocity dependence was not
      observed. Decreased muscle activation and lower maximal voluntary force towards
      the end of the movement suggested inhibition during maximal voluntary eccentric
      actions.

PMID- 16416320
TI  - K+ potentiates hyperosmolarity-induced vasorelaxations in rat skeletal muscle
      arterioles.
AB  - Several regulatory mechanisms have been proposed for the exercise hyperemia in
      skeletal muscles. Since different vasoactive factors might interact during the
      hyperemic response, we investigated the influence of elevated K(+) concentrations
      on hyperosmolarity (HO)-induced vasorelaxations. Small gluteal rat arteries were
      isolated and mounted in an organ bath for isometric tension recording. After
      precontraction with norepinephrine, 20 (S20), 40 (S40) or 60 mM (S60) sucrose was
      added in control conditions (5 mM K(+); K5) or in the presence of additional 3
      (K8) or 5 mM (K10) K(+). Removal of the endothelium and the addition of ouabain,
      Ba(2+), iberiotoxin or 18-alpha glycyrrhetinic acid (alphaGA) were used to study
      the underlying mechanisms. Sucrose evoked significant concentration-dependent
      vasorelaxations (S20 15.62+/-1.61%; S40 26.47+/-1.71%; S60 43.66+/-2.50%), which
      were significantly increased on addition of 3 and 5 mM. After removal of the
      endothelium and in the presence of 5 x 10(-5) M alphaGA, the influence of K(+)
      was significantly blocked but not in the presence of 5 x 10(-5) M ouabain. The
      K(IR) channel inhibitor Ba(2+) and BK(Ca) channel inhibitor iberiotoxin totally
      abolished the potentiating effect. We conclude that K(+) significantly enhances
      the relaxing effect of HO in gluteal blood vessels. We hypothesize that K(+) may
      stimulate the endothelial K(IR) channels which elicits the release of a mediator
      of the BK(Ca) channels. This factor may be transferred through myo-endothelial
      gap-junctions to the smooth muscle cells where modulation of the BK(Ca) channels
      sensitizes the arteries for hyperosmolarity-induced relaxations.

PMID- 16416321
TI  - Effects of the transition time between muscle-tendon stretch and shortening on
      mechanical efficiency.
AB  - The net mechanical efficiency of positive work (eta(pos)) has been shown to
      increase if it is immediately preceded by negative work. This phenomenon is
      explained by the storage of elastic energy during the negative phase and its
      release during the subsequent positive phase. If a transition time (T) takes
      place, the elastic energy is dissipated into heat. The aim of the present study
      was to investigate the relationship between eta(pos) and T, and to determine the
      minimal T required so that eta(pos) reached its minimal value. Seven healthy male
      subjects were tested during four series of lowering-raising of the body mass. In
      the first series (S (0)), the negative and positive phases were executed without
      any transition time. In the three other series, T was varied by a timer (0.12,
      0.24 and 0.56 s for series S (1), S (2) and S (3), respectively). These exercises
      were performed on a force platform sensitive to vertical forces to measure the
      mechanical work and a gas analyser was used to determine the energy expenditure.
      The results indicated that eta(pos) was the highest (31.1%) for the series
      without any transition time (S (0)). The efficiencies observed with transition
      times (S (1), S (2) and S (3)) were 27.7, 26.0 and 23.8%, respectively,
      demonstrating that T plays an important role for mechanical efficiency. The
      investigation of the relationship between eta(pos) and T revealed that the
      minimal T required so that eta(pos) reached its minimal value is 0.59 s.

PMID- 16416322
TI  - The effects of soccer training and timing of balance training on balance ability.
AB  - The purpose of the present study was to investigate the effects of a soccer
      training session on the balance ability of the players and assess whether the
      effectiveness of a balance program is affected by its performance before or after
      the regular soccer training. Thirty-nine soccer players were randomly divided
      into three subject groups (n=13 each), one control group (C group), one training
      group that followed a balance program (12 weeks, 3 times per week, 20 min per
      session) before the regular soccer training (TxB group), and one training group
      that performed the same balance program after the soccer training (TxA group).
      Standard testing balance boards and the Biodex Stability System were used to
      assess balance ability in the C, TxB, and TxA groups at baseline (T0) and after
      completing the balance program (T12). The same tests and additional isokinetic
      knee joint moment measurements were carried out in the TxB and TxA groups pre-
      and post-soccer training. Two main results were obtained: (1) No differences
      (p>0.05) were found in balance ability and knee joint moment production between
      pre- and post-soccer training. (2) The balance program increased (p<0.01) the
      balance ability in the TxB and TxA groups, and the improvement in the TxA group
      was greater (p<0.05) than that in the TxB group post-soccer training. Result (1)
      is in contrast to the notion of a link between fatigue induced by a soccer
      training session or game and injury caused by impaired balance, and result (2)
      has implications for athletic training and rehabilitation.

PMID- 16416323
TI  - Multi-slice DCE-MRI data using P760 distinguishes between metastatic and non
      metastatic rodent prostate tumors.
AB  - An intermediate molecular weight contrast agent P760 was used to investigate the
      ability of multi-slice dynamic contrast-enhanced MRI (DCE-MRI) to distinguish
      metastatic from non-metastatic rodent prostate tumors. Non-metastatic AT2.1 and
      metastatic AT3.1 prostate tumors originally derived from the Dunning prostate
      cancer model were implanted on the hind leg of Copenhagen rats. Multi-sliced DCE
      MRI data were acquired on a SIGNA 1.5 T scanner and analyzed using a recently
      developed empirical mathematical model. The P760 multi-slice DCE-MRI data in
      combination with the empirical mathematical model successfully distinguished
      between metastatic and non-metastatic rodent prostate tumors. Specifically,
      fitting the data with the empirical model showed that metastatic tumors had
      significantly faster contrast media uptake (p<0.001) and slower washout rates
      (p<0.01) than non-metastatic tumors.

PMID- 16416324
TI  - Error images for spectroscopic imaging by LCModel using Cramer-Rao bounds.
AB  - The results of spectroscopic imaging (SI) measurements are often presented as
      metabolic images. If the spectra quality is not sufficient, the calculated
      concentrations are biased and the metabolic images show an incorrect metabolite
      distribution. To simplify the quality analysis of spectra measured by SI, an
      error image, reflecting the accuracy of the computed concentrations, can be
      displayed along with the metabolite image. In this paper the relevance of Cramer
      Rao bounds (CRBs) calculated by the LCModel program to describe errors in
      estimated concentrations is validated using spectra simulations. The relation
      between the average CRBs and standard deviations (STD) of metabolite
      concentrations from 100 simulated spectra for various signal to noise ratio and
      line broadening conditions is evaluated. A parameter for calculating error images
      for metabolite ratios is proposed and an effective way to display error images is
      shown. The results suggest that the average CRBs are strongly correlated with the
      standard deviations and hence that CRB values reflect the relative uncertainty of
      the calculated concentrations. The error information can be integrated directly
      into a metabolite image by displaying only those areas of the metabolite image
      with corresponding CRBs below a selected threshold or by mapping CRBs as a
      transparency of the metabolite image. The concept of error images avoids
      extensive examination of each SI spectrum and helps to reject low quality
      spectra.

PMID- 16416325
TI  - Diagnostic errors in polytrauma: a structured review of the recent literature.
AB  - Clinically important diagnostic errors are relatively common among polytrauma
      patients (2-40%). Errors are not random; they are more frequent in the spine and
      periarticular appendicular skeleton, especially in hemodynamically unstable
      patients who require resuscitation or operative intervention before completion of
      secondary or tertiary clinical survey. Misleading history, distracting findings,
      and misjudgments all contribute to risks of diagnostic errors.

PMID- 16416326
TI  - Back pain and degenerative abnormalities in the spine of young elite divers: a 5
      year follow-up magnetic resonance imaging study.
AB  - Several studies have been published on disc degeneration among young athletes in
      sports with great demands on the back, but few on competitive divers; however,
      there are no long-term follow-up studies. Twenty elite divers between 10 and 21
      years of age, with the highest possible national ranking, were selected at random
      without knowledge of previous or present back injuries or symptoms for an MRI
      study of the thoraco-lumbar spine in a 5-year longitudinal study. The occurrence
      of MRI abnormalities and their correlation with back pain were evaluated. Eighty
      nine percent of the divers had a history of back pain and the median age at the
      first episode of back pain was 15 years. Sixty-five percent of the divers had MRI
      abnormalities in the thoraco-lumbar spine already at baseline. Only one diver
      without abnormalities at baseline had developed abnormalities at follow-up.
      Deterioration of any type of abnormality was found in 9 of 17 (53%) divers.
      Including all disc levels in all divers, the total number of abnormalities
      increased by 29% at follow-up, as compared to baseline. The most common
      abnormalities were reduced disc signal, Schmorl's nodes, and disc height
      reduction. Since almost all divers had previous or present back pain, a
      differentiated analysis of the relationship between pain and MRI findings was not
      possible. However, the high frequency of both back pain and MRI changes suggests
      a causal relationship. In conclusion, elite divers had high frequency of back
      pain at young ages and they run a high risk of developing degenerative
      abnormalities of the thoraco-lumbar spine, probably due to injuries to the spine
      during the growth spurt.

PMID- 16416328
TI  - Cloning of the astaxanthin synthase gene from Xanthophyllomyces dendrorhous
      (Phaffia rhodozyma) and its assignment as a beta-carotene 3-hydroxylase/4
      ketolase.
AB  - A gene has been cloned from Xanthophyllomyces dendrorhous by complementation of
      astaxanthin formation in a beta-carotene accumulating mutant. It consists of
      3,166 bp and contains 17 introns. For the beta-carotene mutant ATCC 96815, a
      single point mutation in the splicing sequence of intron 8 was found. The
      resulting improper splicing of the mRNA results in an inactive protein. The cDNA
      of this beta-carotene oxygenase encodes a cytochrome P450 monooxygenase belonging
      to the 3A subfamily. P450-specific domains were identified including a cytochrome
      P450 and an oxygen binding motif. Electrons are provided by a cytochrome P450
      reductase. Functional characterization of the enzyme by genetic modification of
      X. dendrorhous demonstrated that this P450 monooxygenase is multifunctional
      catalyzing all steps from beta-carotene to astaxanthin formation by oxygenation
      of carbon 3 and 4. The reaction sequence is first 4-ketolation of beta-carotene
      followed by 3-hydroxylation. A hydroxylation mechanism at allylic carbon atoms
      has been proposed for the generation of 4-keto and 3-hydroxy groups at both beta
      ionone ends.

PMID- 16416329
TI  - Respiratory gating of cardiac PET data in list-mode acquisition.
AB  - PURPOSE: Respiratory motion has been identified as a source of artefacts in most
      medical imaging modalities. This paper reports on respiratory gating as a means
      to eliminate motion-related inaccuracies in PET imaging. METHODS: Respiratory
      gating was implemented in list mode with physiological signal recorded every
      millisecond together with the PET data. Respiration was monitored with an
      inductive respiration monitor using an elasticised belt around the patient's
      chest. Simultaneous ECG gating can be maintained independently by encoding ECG
      trigger signal into the list-mode data. Respiratory gating is performed in an off
      line workstation with gating parameters defined retrospectively. The technique
      was applied on a preliminary set of patient data with C(15)O. RESULTS: Motion was
      visually observed in the cine displays of the sagittal and coronal views of the
      reconstructed respiratory gated images. Significant changes in the cranial-caudal
      position of the heart could be observed. The centroid of the cardiac blood pool
      showed an excursion of 4.5-16.5 mm (mean 8.5+/-4.8 mm) in the cranial-caudal
      direction, with more limited excursion of 1.1-7.0 mm (mean 2.5+/-2.2 mm) in the
      horizontal direction and 1.3-3.7 mm (mean 2.4+/-0.9 mm) in the vertical
      direction. CONCLUSION: These preliminary data show that the extent of motion
      involved in respiration is comparable to myocardial wall thickness, and
      respiratory gating may be considered in order to reduce this effect in the
      reconstructed images.

PMID- 16416330
TI  - Uptake of bone-seekers is solely associated with mineralisation! A study with
      99mTc-MDP, 153Sm-EDTMP and 18F-fluoride on osteoblasts.
AB  - PURPOSE: Although polyphosphonates (PPs) were introduced as bone imaging agents
      in nuclear medicine in the early 1970s, the mechanisms involved in their uptake
      still remain unclear. Suggested mechanisms range from mineral adsorption with
      disputed binding to the organic phase, over incorporation into the mineralisation
      process to a combination of both mechanisms. Thus, our investigations aimed to:
      (1) evaluate adsorption parameters of (99m)Tc-MDP, (153)Sm-EDTMP and (18)F
      fluoride on mineralising osteoblast cultures, (2) correlate the radiotracer
      binding measured in the cell cultures with binding values from our previously
      presented mineral model and (3) compare binding with cell number. METHODS:
      Primary osteoblasts were obtained by sequential digestion of foetal mice
      calvariae. The cells were incubated with 0.3 mumol of radiolabelled PPs or 25 MBq
      (18)F-fluoride for 120 min. Gamma signals from labelled samples were detected
      with a Millennium Hawkeye SPECT camera or with a dedicated Advance full-ring PET
      scanner and the binding percentages were calculated. RESULTS: From days 8 to 15
      of culture, the percent binding of all evaluated tracers increased significantly,
      whereas the protein concentration showed insignificant changes. Additional
      comparisons of the binding values with our recently published pre-vivo model
      revealed remarkable agreement, suggesting solely bone-forming minerals to be
      responsible for radiotracer binding. CONCLUSION: This study provides evidence
      that binding of the evaluated radiotracers is not associated with osteoblast
      numbers but only with the concentration of bone-forming minerals. The presented
      correlations substantiate our recently presented pre-vivo model for the
      evaluation of bone-seekers: mechanisms associated with the uptake of bone-seekers
      are irreversible and mineral-associated processes.

PMID- 16416331
TI  - Neonatal treatment with a competitive NMDA antagonist results in response
      specific disruption of conditioned fear in preweanling rats.
AB  - RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been implicated in
      processes of neurodevelopment, including cell proliferation, synaptogenesis, and
      apoptosis. Several studies have reported that administration of NMDA antagonists
      early in development can cause long-lasting changes in behavior. For example,
      Gould and Cameron [Behav Neurosci 111:49-56 (1997a)] have shown that a single
      injection of the competitive NMDA antagonist CGP 43487 on postnatal day (PD) 5
      affected behavioral immobility in young rats exposed to the odor of a natural
      predator. OBJECTIVES: This experiment was undertaken to determine whether the
      behavioral effects previously reported would also be seen with conditioned cues.
      Both stimulus-elicited behavioral immobility (freezing) and changes in heart rate
      were recorded to examine impairments in responding across multiple measures.
      METHODS: Animals were given a single injection of 0, 2.5, or 5.0 mg/kg CGP 43487
      on PD 5. On PD 20 subjects were given paired or unpaired presentations of either
      an olfactory or auditory conditioned stimulus (CS) with a 110-dB-white-noise
      unconditioned stimulus. CS-elicited freezing and changes in heart rate were
      measured. RESULTS: Pups treated with CGP exhibited impairments in conditioned
      freezing, but were unaffected in their expression of conditioned changes in heart
      rate, to both olfactory and auditory stimuli. CONCLUSIONS: These results indicate
      that neonatal treatment with an NMDA antagonist affects the expression of fear in
      a response-specific manner. The data suggest that antagonist-induced alterations
      in neural systems involved in the expression of freezing are affected by NMDA
      receptor blockade early in life.

PMID- 16416332
TI  - Effect of creatine supplementation and sleep deprivation, with mild exercise, on
      cognitive and psychomotor performance, mood state, and plasma concentrations of
      catecholamines and cortisol.
AB  - RATIONALE: Sleep deprivation has a negative effect on cognitive and psychomotor
      performance and mood state, partially due to decreases in creatine levels in the
      brain. Therefore, creatine supplementation should lessen the negative effects of
      sleep deprivation. OBJECTIVES: The objective of this study was to examine the
      effect of creatine supplementation and sleep deprivation, with mild exercise, on
      cognitive and psychomotor performance, mood state, and plasma concentrations of
      catecholamines and cortisol. METHOD: Subjects were divided into a creatine group
      (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a
      placebo, dependent on their group, four times a time a day for 7 days,
      immediately prior to the experiment. The study was double blind. Subjects
      undertook tests of random movement generation (RMG), verbal and spatial recall,
      choice reaction time, static balance and mood state pre-test (0 h), after 6, 12
      and 24 h of sleep deprivation, with intermittent exercise. They were tested for
      plasma concentrations of catecholamines and cortisol at 0 and 24 h. RESULTS: At
      24 h, the creatine group demonstrated significantly less change in performance
      from 0 h (delta) in RMG, choice reaction time, balance and mood state. There were
      no significant differences between groups in plasma concentrations of
      catecholamines and cortisol. Norepinephrine and dopamine concentrations were
      significantly higher at 24 h than 0 h, but cortisol were lower. CONCLUSIONS:
      Following 24-h sleep deprivation, creatine supplementation had a positive effect
      on mood state and tasks that place a heavy stress on the prefrontal cortex.

PMID- 16416334
TI  - Phase I/II study of weekly docetaxel dose escalation in combination with fixed
      weekly cisplatin and concurrent thoracic radiotherapy in locally advanced non
      small cell lung cancer.
AB  - PURPOSE: We conducted a phase I study to determine the maximum-tolerated dose
      (MTD) and dose-limiting toxicities (DLT) of weekly docetaxel and cisplatin
      (DOC/CDDP) with concurrent thoracic radiotherapy (TRT) in patients with
      unresectable stage III non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS:
      The DOC/CDDP administration schedules consisted of a split schedule (SS) with
      administration in 3 out of every 4 weeks, and a continuous schedule (CS) with
      administration every week. TRT was given to a total dose of 60 Gy at 2 Gy per
      fraction over 6 weeks. RESULTS: Twenty-one patients entered the study. The
      patient characteristics were: PS 0/1/2, 6/13/2; Sq/Ad, 16/5; stage IIIA/IIIB,
      4/17. The principal DLT was grade3 esophagitis. The MTD of DOC on the SS and CS
      in combination with CDDP (25 mg/m2/week) was 25 and 20 mg/m(2)/week,
      respectively. We determined the RD and schedule of DOC/CDDP on the SS to be 20/25
      mg/m(2)/week. The serum alpha-1-acid glycoprotein (AAG) concentration values were
      found to be negatively correlated with the grade of esophagitis. The median
      survival time was 23.1 months. CONCLUSION: The chemoradiation regimen tested in
      this study has promising activity and manageable toxicity. The continuous
      schedule could not be recommended due to excessive toxicity. The main DLT was
      esophagitis, and it significantly correlated with the plasma AAG concentration.

PMID- 16416335
TI  - Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with
      urothelial cancer who had received prior cisplatin-based therapy.
AB  - BACKGROUND AND AIMS: The aim of the present phase II study was to evaluate the
      efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin
      (PIN regimen) in patients with recurrent urothelial cancer who had been treated
      with cisplatin-based chemotherapy. PATIENTS/METHODS: Eligible patients were those
      with histologically confirmed urothelial cancer who had progressed or relapsed
      after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175
      mg/m(2) on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and
      nedaplatin 70 mg/m(2) on day 1; PIN was given every 28 days. RESULTS: Among the
      32 patients enrolled in the study (median age, 66 years), complete and partial
      responses were obtained in 5 patients and 19 patients, respectively, with an
      overall response rate of 75% (95% confidence interval [CI], 59-91%). The median
      time to progression was 8 months (range, 0-50+ months) and the median survival
      was 22 months (range, 4-52+ months). The 1- and 2-year overall survival rates
      were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4
      neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3
      or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient,
      for whom the PIN therapy was discontinued. There were no treatment-related
      deaths. CONCLUSION: The PIN combination was highly active and tolerable in
      previously treated patients with urothelial cancer as a second-line treatment.

PMID- 16416336
TI  - Stimulation of the epithelial sodium channel (ENaC) by the serum- and
      glucocorticoid-inducible kinase (Sgk) involves the PY motifs of the channel but
      is independent of sodium feedback inhibition.
AB  - The epithelial sodium channel (ENaC) is the major mediator of sodium transport
      across the apical membranes of the distal nephron, the distal colon, the
      respiratory tract and the ducts of exocrine glands. It is subject to feedback
      inhibition by increased intracellular Na+, a regulatory system wherein the
      ubiquitin protein ligases, Nedd4 and Nedd4-2, bind to conserved PY motifs in the
      C-termini of ENaC and inactivate the channel. It has been proposed recently that
      the kinase Sgk activates the channel as a consequence of phosphorylating Nedd4-2,
      thus preventing it from inhibiting the channels. This proposal predicts that Sgk
      should interfere with Na+ feedback regulation of ENaC. We have tested this
      prediction in Xenopus laevis oocytes and in mouse salivary duct cells and found
      that in neither system did increased activity of Sgk interrupt Na+ feedback
      inhibition of ENaC. We found, however, that Sgk stimulation was largely abolished
      in oocytes expressing ENaC channels with C-terminal truncations or mutated PY
      motifs. We were also unable to confirm that Sgk directly interacts with Nedd4-2
      in vitro. We conclude that the stimulatory effect of Sgk on ENaC requires the
      presence of the channel's PY motifs, but it is not due to the interruption of Na+
      feedback regulation.

PMID- 16416342
TI  - [Mild cognitive impairment].

PMID- 16416333
TI  - Neurosteroids and cholinergic systems: implications for sleep and cognitive
      processes and potential role of age-related changes.
AB  - RATIONALE: The neurosteroids pregnenolone sulfate (PREGS), dehydroepiandrosterone
      sulfate (DHEAS) and allopregnanolone (3alpha,5alpha THPROG) have been implicated
      as powerful modulators of memory processes and sleep states in young and aged
      subjects with memory impairment. As these processes depend on the integrity of
      cholinergic systems, a specific effect of neurosteroids on these systems may
      account for their effects on sleep and memory. OBJECTIVE: To review the evidence
      for a specific and differential effect of neurosteroids on cholinergic systems.
      METHODS: We carried out keyword searches in "Medline" to identify articles
      concerning (1) the effects of neurosteroids on cholinergic systems, sleep and
      memory processes, and (2) changes in neurosteroid concentrations during aging.
      Few results are available for humans. Most data concerned rodents. RESULTS:
      Peripheral and central administrations of PREGS, DHEAS, and 3alpha,5alpha THPROG
      modulate the basal forebrain and brainstem projection cholinergic neurons but not
      striatal cholinergic interneurons. Local administration of neurosteroids to the
      basal forebrain and brainstem cholinergic neurons alters sleep and memory in
      rodents. There are a few conflicting reports concerning the effects of aging on
      neurosteroid concentrations in normal and pathological conditions. CONCLUSIONS:
      The specific modulation of basal forebrain and brainstem cholinergic systems by
      neurosteroids may account for the effects of these compounds on sleep and memory
      processes. To improve our understanding of the role of neurosteroids in
      cholinergic systems during normal and pathological aging, we need to determine
      whether there is specific regionalization of neurosteroids, and we need to
      investigate the relationship between neurosteroid concentrations in cholinergic
      nuclei and age-related sleep and memory impairments.

PMID- 16416343
TI  - [Thymoma].
AB  - Thymoma is a rare epithelial tumor of the thymus, but the most common malignancy
      in the anterior mediastinum. A unique feature is its association with
      paraneoplastic syndromes, in particular myasthenia gravis. According to the WHO
      classification 6 histologic types of thymic epithelial tumors can be
      discriminated. Tumor stage according to MASAOKA is the most important prognostic
      factor. Non-invasive tumors (stage I) are usually completely resected and no
      further therapy is warranted. For incompletely resected tumors and locally
      advanced invasive thymomas (stage Ill-IV) postoperative radiotherapy with 50-60
      Gy is advisable. Chemotherapy, preferably with Cisplatinum, is indicated with
      inoperable thymomas or metastatic disease. In general thymomas have a fair
      prognosis even in advanced stage. Long term follow-up is mandatory up to 10
      years.

PMID- 16416344
TI  - Periosteal ganglion of the tibia.

PMID- 16416337
TI  - Improved therapeutic outcomes of DLBCL after introduction of rituximab in Korean
      patients.
AB  - The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP) has been shown to improve the outcome in all age groups with
      newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a
      retrospective analysis to evaluate the impact of this combination therapy on
      DLBCL outcomes in Korea. From October 2001 to June 2004, newly diagnosed DLBCL
      patients in nine Korean institutes were included. All of these 81 patients were
      treated with three or more cycles of rituximab plus CHOP (R-CHOP) combination
      chemotherapy (R group), and followed for a minimum of 12 months. For comparison,
      a historical cohort of patients was used and analyzed for "Clinicopathologic
      characteristics of Korean non-Hodgkin's lymphomas (NHLs) based on Revised
      American Lymphoma (REAL) classification" in 1999. Among the 1,098 NHL patients,
      the data of 214 DLBCL patients, who were treated with CHOP chemotherapy in first
      line, were analyzed (C group). We compared outcomes between the C group and the R
      group. A total of 295 patients were evaluated (C group, 214; R group, 81). The
      complete response (CR) rate was higher in R group (73 vs 91%, p=0.001). The 2
      year event-free survival (EFS) rate was significantly higher in R group (78 vs
      85%, p=0.0194). This survival benefit was maintained in high-risk patients
      according to the international prognostic index (IPI) (p=0.0039), regardless of
      age. However, there was no significant difference in low-risk patients. The
      addition of rituximab to CHOP combination chemotherapy for DLBCLs showed improved
      outcomes, particularly in high-risk group according to the IPI. Long-term follow
      up results will be needed to confirm these results.

PMID- 16416345
TI  - Annual conversion to alzheimer disease among patients with memory complaints
      attending an outpatient memory clinic: the influence of amnestic mild cognitive
      impairment and the predictive value of neuropsychological testing.
AB  - OBJECTIVE: The goals of this study were to determine the annual conversion rate
      to Alzheimer disease (AD) among patients reporting memory problems, including a
      subgroup with amnestic mild cognitive impairment (aMCI), and to investigate the
      predictive value of neurocognitive testing for future dementia. METHODS: A
      prospective study was carried out in an outpatient memory clinic. One hundred and
      seven patients underwent a clinical examination and completed a battery of
      standard cognitive tests at study entry and two years later. The conversion rate
      to clinically manifested AD two years later was investigated and sensitivity,
      specificity, receiver operating characteristics (AUC), positive predictive value
      and negative predictive value for each neuropsychological test were determined.
      RESULTS: We found an annual rate of conversion to AD of 6.5% among patients
      reporting memory decline in the setting of our clinic. Specifically, patients
      with aMCI had an annual conversion rate of approximately 20%. The annual
      conversion rate for patients reporting memory problems but showing no memory
      deficit at memory testing was approximately 3%. Receiver operating
      characteristics (AUC) of the neuropsychological tests ranged from 0.60 to 0.94.
      CONCLUSIONS: Patients with aMCI have 8.6-fold higher odds of developing AD
      compared with patients without evident memory impairment on neuropsychological
      testing. Although the risk of developing AD among patients without objective
      memory decline is small, some patients in this group still convert to AD and
      therefore close clinical monitoring of patients is necessary.

PMID- 16416346
TI  - TSH may not be a good marker for adequate thyroid hormone replacement therapy.
AB  - The objective of this study was to evaluate parameters of thyroid function and
      indices of peripheral thyroid hormone action (such as SHBG) in patients whose
      hypothyroidism was considered well controlled under current criteria. Eighty-five
      patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared
      with 114 normal individuals with the same TSH levels. T3 levels were
      significantly lower in hypothyroidism although mean T4 and fT4 levels were
      significantly higher. Furthermore, mean SHBG levels were significantly lower in
      hypothyroidism independently of age. The difference remained when stricter
      criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant
      negative correlations were found between logTSH and T3. The slopes of the
      regression lines of T3 to TSH were significantly different in the control group
      and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in
      the hypothyroid group. We conclude that patients with T4-treated hypothyroidism
      have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals
      with the same TSH, perhaps indicating relative tissue hypothyroidism in the
      liver. TSH levels used to monitor substitution, mostly regulated by intracellular
      T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone
      action in all tissues. The co-administration of T3 may prove more effective in
      this respect, provided novel suitable preparations are developed. Until this is
      accomplished, substitution in hypothyroidism should aim at low normal TSH, to
      ensure normal T3 levels.

PMID- 16416347
TI  - [Evaluation of the Austrian Newborn Hearing Screening Program].
AB  - BACKGROUND: Universal Neonatal Hearing Screening (UNHS) has been gradually
      implemented since the mid-nineties in Austrian maternity wards and neonatal
      intensive care units. This study evaluated the effect of UNHS on reducing age at
      identification as well as age of intervention for children with congenital and
      perinatal sensorineural hearing impairment. METHODS: This was a retrospective
      analysis of clinical data of 394 Austrian children diagnosed with an at least
      mild degree (> 20 dB hearing level) of permanent sensorineural hearing loss. Age
      at identification and age at intervention were compared between children who
      underwent UNHS ('with UNHS') and those who did not undergo UNHS ('without UNHS').
      RESULTS: The median of age of identification was 37.6 months in children without
      UNHS, and 3.9 months in children with UNHS. By six months of age, 69% of hearing
      impaired children who underwent UNHS, were identified but only 6% of those
      without UNHS. At one year, the corresponding percentages are 80% and 12%,
      respectively. In children without UNHS, the degree of hearing loss was the most
      predictive factor of age at identification (median of age at diagnosis for
      profound hearing loss: 15 months; severe: 26 months; moderate: 52 months; mild:
      73 months). In children with UNHS, age of identification was unrelated to degree
      of hearing loss (medians between 3.7 and 4.4 months). In the majority of children
      intervention began within one month after diagnosis, regardless of whether or not
      the child was identified by UNHS. DISCUSSION: UNHS greatly increases the
      proportion of children whose hearing impairment is diagnosed before six months of
      age. However, in some 20% of children, hearing impairment was diagnosed later
      than one year of age, despite having failed the screening. Additionally, data
      from this study suggest that about 15% of childhood hearing losses manifest
      themselves after the hearing screening period. Efforts are thus required for the
      early detection of these children as well.

PMID- 16416348
TI  - Recurrent symptomatic bradycardia due to secret ingestion of beta-blockers--a
      rare manifestation of cardiac Munchhausen syndrome.
AB  - The term Munchhausen syndrome was established in 1951 by Asher to describe a
      severe psychiatric illness in which patients simulate false symptoms and signs.
      We report on a female general practitioner who repeatedly ingested high doses of
      beta-blockers in order to simulate symptomatic sick-sinus syndrome. She had been
      admitted to intermediate care units in several hospitals before the correct
      diagnosis was made by finding the tablets in her toilet bag. Following
      psychiatric exploration and psychotherapy, she has been working in her community
      again for about a year. This is the first report on the clinical presentation and
      course of disease in a patient with cardiac Munchhausen syndrome who secretly
      ingested beta-blockers to provoke a menacing bradycardia. The follow-up indicates
      that frequent and intense symptomatic episodes of this remarkable psychiatric
      disease can be interrupted by long normal intervals.

PMID- 16416349
TI  - [Examination of pulmonary circulation using right heart catheterization. Position
      paper of the Cardiopulmonary Task Force of the Austrian Society for Pneumology
      and the Austrian Society for Cardiology].

PMID- 16416352
TI  - [The first preimplantation diagnosis in Austria].

PMID- 16416353
TI  - [Strontium ranelate: a novel concept for the treatment of osteoporosis].
AB  - The di-strontium salt strontium ranelate, a novel orally active agent consisting
      of two atoms of stable strontium and the organic moiety ranelic acid, has been
      developed for the treatment of osteoporosis. It has been shown to enhance
      osteoblastic cell replication and increase collagen synthesis while decreasing
      pre-osteoclast differentiation and bone-resorbing activity of mature osteoclasts
      in vitro. Studies performed in healthy animals have shown that strontium ranelate
      not only increases bone mass at various skeletal sites but also improves
      mechanical properties of femoral, humeral and vertebral bones. In estrogen
      deficient animals, strontium ranelate effectively inhibits increased bone
      resorption while maintaining bone formation. Similar results have been obtained
      from studies in hind limb-immobilized animals. Strontium ranelate has been
      investigated in a large phase III program which includes two extensive
      multinational, randomized, double-blind, placebo-controlled clinical trials for
      the treatment of severe postmenopausal osteoporosis. Before inclusion in these
      two studies, patients were subjected to a run-in study in order to initiate
      normalization of their calcium and vitamin D status. The SOTI study, aimed at
      assessing strontium ranelate's effect on the risk of vertebral fractures,
      revealed a significant reduction in the risk of new vertebral fractures in the
      group treated with strontium ranelate. The TROPOS study, which aimed at
      evaluating the effect of strontium ranelate on nonvertebral fractures, showed a
      significant reduction in the risk of new nonvertebral fractures and also, in a
      high-risk subgroup, a significant reduction in the risk of hip fractures. In both
      studies, the reduction in fracture risk was accompanied by an increase in bone
      mineral density. The increase remained significant also after correction of the
      bone mineral density for the higher atomic mass of strontium compared to calcium.
      Furthermore, an increase in serum levels of a bone formation marker and a
      decrease in serum levels of a bone resorption marker were observed. The spectrum
      of side effects comprised mild diarrhea, particularly within the first weeks of
      treatment, and also a slightly increased risk of venous thromboembolic events.
      Strontium ranelate thus appears to be a new, effective treatment to prevent
      fractures in postmenopausal osteoporosis with a novel mechanism of action. It can
      be expected for the near future that strontium ranelate will also be evaluated
      for other types of osteoporosis, such as male osteoporosis.

PMID- 16416354
TI  - Pneumococcal meningoencephalitis.

PMID- 16416355
TI  - Mortality and morbidity in extremely preterm infants (22 to 26 weeks of
      gestation): Austria 1999-2001.
AB  - OBJECTIVE: The aim of this retrospective study was to analyze the mortality and
      morbidity for extremely preterm infants with a gestational age from 22 to 26
      weeks. All infants were born in Austria during the years 1999-2001. METHODS: Data
      were collected from 16 neonatal intensive care units in Austria. Main outcome
      criteria were mortality, the rates of chronic lung disease (CLD) and severe
      retinopathy of prematurity (ROP, stage > or =3) to determine the short-term
      outcome; the rate of cerebral palsy (CP) at the corrected age of twelve months to
      assess the long-term outcome. RESULTS: Overall, 796 preterm infants with a
      gestational age less than 27 weeks were born in Austria and 581 (73%) were
      registered as live-born infants. Of those live born, 508 (87%) were analyzed. The
      mortality rates were 83%, 76%, 43%, 26% and 13% for 22, 23, 24, 25 and 26 weeks'
      gestation, respectively. The rates of CLD were 33% (22 weeks), 36% (23 weeks),
      42% (24 weeks), 31% (25 weeks) and 22% (26 weeks). The rates of ROP of stage > or
      =3 were 0% (22 weeks), 29% (23 weeks), 23% (24 weeks), 18% (25 weeks) and 10% (26
      weeks). The rates of CP at the corrected age of 12 months were 33%, 50%, 33%, 26%
      and 25% for 22, 23, 24, 25 and 26 weeks' gestation, respectively. CONCLUSIONS:
      The results of this national study are in accordance with the international
      literature: mortality and morbidity increased with decreasing gestational age.

PMID- 16416356
TI  - Efficacy of a neuropsychological training programme for patients with multiple
      sclerosis -- a randomised controlled trial.
AB  - BACKGROUND: One aim of this project was to investigate the efficacy of a specific
      training programme for MS patients which also contained compensation strategies
      and relaxation exercises relevant to everyday life. The other aim was to check
      the programme's relevance to everyday life. METHOD: 19 patients, randomised into
      two groups, took part in the study. The participants in the treated group
      completed a specific neurological training programme which began immediately
      after the basic testing (visit 1) and lasted 4 weeks, with a total of 12
      sessions. The monitoring test was done immediately after the training programme
      (at visit 2) and the follow-up was 3 months later (visit 3). Both study groups
      were fully comparable as regards clinical and socio-demographic data and baseline
      intelligence level. RESULTS: The results of the cognitive training programme were
      especially evident in the significant improvements in executive functions (CKV)
      and spatial-constructional abilities (HAWIE-R). Comparison between the treated
      and the control group showed no significant difference in the fatigue values
      (MFIS). However, when the treated group was examined over the three times of
      measurements, the symptoms of fatigue had diminished significantly. Regarding
      memory, comparison of the groups showed no changes; within the treated group;
      however, the verbal (VLT) and nonverbal learning and memory (NVLT) improved
      significantly. The results for sustained attention improved in both groups over
      time. It must be assumed that a learning effect had occurred here. The depression
      values (BDI) also improved in both study groups. The follow-up questionnaire
      showed that 60% (6) attributed an average to above-average benefit to the
      training. CONCLUSION: To summarise, it is apparent that MS patients with mild to
      moderate cognitive impairment are able to profit from even a fairly brief
      neuropsychological training programme and to integrate much of it into their
      everyday lives. In view of this, it would seem appropriate to offer such a
      programme as standard, associated with medication.

PMID- 16416357
TI  - No cognitive deficits in men formerly exposed to lead.
AB  - OBJECTIVES: The objective of the study was to investigate long-term cognitive
      effects resulting from low to moderate lead exposure below current threshold
      values. Executive functions, attention, visuospatial and visuomotor functioning
      in workers formerly exposed to lead were investigated. METHODS: 48 men formerly
      exposed to lead and with a mean current blood level (PbB) of 5.4 microg Pb/100 ml
      were investigated, together with 48 matched controls (PbB, 4.7 microg Pb/100 ml)
      out of a pool of 61 males. The two groups were matched for age, years spent in
      education, verbal intelligence and gram alcohol consumption per week. The
      following neuropsychological tests were used: modified Wisconsin card sorting
      test, block design test, visual recognition test, simple reaction time, choice
      reaction and digit-symbol substitution. Lead exposure was assessed using both
      current and cumulative measurements. RESULTS: There were no significant
      differences in cognitive parameters between the two groups. When analyzing dose
      response relationships, negative correlations were found between PbB and
      performance in the block design test, and between PbB and scores in the visual
      recognition and digit-symbol substitution tests. High cumulative exposure (IBL,
      >5000; duration of exposure, >5 years) correlated only with wrong reactions in
      the choice reaction test. CONCLUSIONS: The results of our study indicate that
      cognitive deficits resulting from low-level exposure to lead are reversible. The
      study was limited to low-level long-term exposure (all PbB values were always
      below 55 microg Pb/100 ml), and extrapolation of these results to persons heavily
      exposed to lead is not possible.

PMID- 16416358
TI  - Chronic pelvic pain treated with gabapentin and amitriptyline: a randomized
      controlled pilot study.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and side effects of
      gabapentin, amitriptyline, and their combination in women with chronic pelvic
      pain. METHODS: In this open-label, prospective, randomized trial, 56 women with
      chronic pelvic pain were investigated with a two-year follow-up at the Vienna
      Medical University Hospital. If pain intensity assessed by a visual analog scale
      (VAS) was 5 or more (0, no pain; 10, maximal pain), despite analgesic therapy
      using the nonopioid drug metamizol together with weak opioids, patients were
      randomized to receive gabapentin (n = 20), amitriptyline (n = 20), or a
      combination of both drugs (n = 16). Doses of gabapentin and amitriptyline were
      increased to maximum daily doses of 3600 mg and 150 mg, respectively, until
      sufficient pain relief or the occurrence of side effects. VAS and side effects
      were evaluated before treatment and at 1, 3, 6, 12 and 24 months afterwards.
      RESULTS: All patients experienced significant pain relief during the observation
      period. However, after 6, 12 and 24 months, pain relief was significantly better
      in patients receiving gabapentin either alone or in combination with
      amitriptyline than in patients receiving monotherapy with amitriptyline
      (gabapentin: 0 months, 7.7 +/- 1.5; 6 months, 1.6 +/- 0.9; 12 months, 1.5 +/-
      0.9; 24 months, 1.9 +/- 0.9; amitriptyline: 0 months, 7.3 +/- 1.5; 6 months, 2.2
      +/- 1.6; 12 months, 2.2 +/- 1.6; 24 months; 3.4 +/- 0.9; amitriptyline
      gabapentin: 0 months, 7.6 +/- 0.8; 6 months, 1.3 +/- 0.9; 12 months, 1.7 +/- 1.0;
      24 months, 2.3 +/- 0.9). Side effects were lower in the gabapentin group than in
      the two other groups, the difference reaching statistical significance after
      three months (P < 0.05). CONCLUSION: Gabapentin alone or in combination with
      amitriptyline is better than amitriptyline alone in the treatment of female
      chronic pelvic pain.

PMID- 16416359
TI  - Comparison of mouth-to-mouth resuscitation and Combitube ventilation in a bench
      model.
AB  - CONTEXT: In addition to heart massage, the primary goal of cardiopulmonary
      resuscitation is efficient oxygenation and ventilation. OBJECTIVE: To compare the
      ease of learning and handling of standard mouth-to-mouth resuscitation with the
      Combitube (Tyco Healthcare Nellcor, Pleasanton, CA) ventilation. METHODS: After a
      30 minute theoretical introduction and demonstration of mouth-to-mouth
      resuscitation and use of the Combitube in mannequins, following American Heart
      Association guidelines, 26 adolescent school children (15 of them 14 years old,
      11 of them 10 years old) undertook two ventilation trials, each consisting of
      five single ventilations, with each technique. Only the second trial with each
      technique was evaluated. Qualitative implementation (grades: very good, good,
      failed) was evaluated, several procedure-related time points were recorded, and
      tidal volumes (ml) were measured. RESULTS: With mouth-to-mouth resuscitation, the
      time interval until start of first ventilation was 36.5 seconds shorter than with
      the Combitube (P < 0.001). With the Combitube, the time needed for five single
      ventilations was 6.4 seconds less than with mouth-to-mouth resuscitation (P <
      0.001) and mean tidal volumes were higher (mouth-to-mouth resuscitation, 450 +/-
      384 ml, versus Combitube, 735 +/- 358 ml; P < 0.05). CONCLUSION: Most of the
      school children performed both techniques to a high qualitative level. The study
      shows that mouth-to-mouth resuscitation and use of the Combitube have equal ease
      of learning, a precondition for proficient retention of skills. Tidal volumes
      were significantly higher with the Combitube and, not surprisingly, the time
      interval until the start of first ventilation was significantly shorter with
      mouth-to-mouth resuscitation. Regardless of the ventilation technique or device,
      we believe that subsequent retraining of ventilation skills is very important.

PMID- 16416360
TI  - Annoying vacation souvenir: Fish tapeworm (Diphyllobothrium sp.) infestation in
      an Austrian fisherman.
AB  - Diphyllobothriosis is infestation with the fish tapeworm. Although the worldwide
      incidence has decreased in recent decades, increased travel and the new
      popularity of dishes involving raw fish (e.g. sushi) may provide a higher risk of
      infestation in formerly low-risk areas. We report an Austrian fisherman who
      passed a 75 cm tapeworm segment in his stool. Infestation presumably occurred 14
      months earlier during a fishing tour in Alaska. At presentation, the patient was
      asymptomatic, reported no weight loss and showed neither anaemia nor
      eosinophilia. He was cured with a single dose of 10 mg/kg body weight
      praziquantel.

PMID- 16416361
TI  - Large complex odontoma of the left maxillary sinus.
AB  - Odontomas as a group are the most common odontogenic neoplasms. They are mixed
      lesions containing fully formatted dental tissues, both epithelial and
      mesenchymal, and are usually found during a routine radiographic examination or
      as a factor in noneruption. Odontomas can be divided into two types: the complex
      and the compound odontoma. Both types are composed of enamel, dentin, cementum
      and pulp tissues, but in complex odontomas the tissues are arranged in a
      haphazard fashion with no discernible dental structures, whereas in compound
      odontomas the dental tissues exist in a more regular pattern so that the lesion
      consists of tooth-like structures. We report a case of a 23-year-old man with a
      large complex odontoma involving the left maxilla and maxillary sinus with
      clinical, radiographic and histological findings. Because of the size of the mass
      and its clinical course, benign neoplasms were considered in the differential
      diagnosis. Surgery was the treatment of choice, and recurrence of the lesion is
      not expected.

PMID- 16416364
TI  - [Diet therapy for cancer patients--"in the beginning for few, in the end for
      many"].

PMID- 16416365
TI  - [L-arginine: an amino acid with multiple effects].

PMID- 16416366
TI  - [Guidelines for the planning and implementation of telemedical applications].
AB  - Before a telemedical application can be implemented in practice, various
      technical, organisational, and legal questions have to be solved. The answers to
      these questions are, however, in most cases not very obvious. Telemedicine
      guidelines which could provide a path to follow currently exist only for selected
      medical fields and are frequently customized for particular medical and technical
      scenarios. The use of existing telemedicine guidelines in Austrian health care is
      further complicated by the fact that most of them are based on foreign legal
      systems. This paper therefore aims to develop general telemedicine guidelines
      which are appropriate for all application areas of telemedicine in Austrian
      health care. From nine existing telemedicine guidelines for individual medical
      fields, two generally applicable guidelines were derived. The corresponding
      abstraction process was based on a categorization of telemedical applications,
      which is oriented on the communication partners involved. The derived, general
      guidelines address seven typical problem domains in the practical application of
      a telemedical application. As opposed to the existing guidelines, they (1) are
      independent of special medical fields and are therefore appropriate for all
      application areas of telemedicine -- also in medical fields where no specific
      guidelines have existed before; (2) are adapted to the Austrian legal system; (3)
      provide additional insight for medical fields where specific guidelines have
      already existed, as they can benefit from recommendations of other medical fields
      where equivalent telemedical applications are employed.

PMID- 16416367
TI  - Faint and dyspnea as the first clue to diagnosis of pulmonary carcinoid.

PMID- 16416368
TI  - Effects of a high-fat diet on body composition in cancer patients receiving
      chemotherapy: a randomized controlled study.
AB  - BACKGROUND: Patients with cancer are characterized by a profound impairment of
      glucose utilization, with lipids being the preferred metabolic fuel. In contrast,
      the energy needs of malignant tumors are almost entirely met by glucose. We
      therefore studied the effects of a high-fat diet, particularly on body
      composition. PATIENTS AND METHODS: Twenty-three moderately malnourished patients
      with gastrointestinal carcinomas were randomized to receive either a conventional
      diet supplying 35 nonprotein kcal and 1.1 g of protein/kg per day (group A, n =
      11) or a fat-enriched artificial liquid diet (20 nonprotein kcal/kg per day) plus
      normal meals (group B, n = 12) for a period of eight weeks, i.e., from the first
      to the third chemotherapy cycle. The fat content of the artificial diet was 66%
      of the nonprotein calories. The day before the nutritional interventions, and
      again after four and eight weeks, body compartments were determined using
      bioelectrical impedance analysis, lymphocyte subpopulations were quantified using
      flow cytometry, and some aspects of the quality of life were rated using four
      linear analog self-assessment (LASA) scales. The statistical calculations were
      done as an exploratory data analysis. RESULTS: The consumption of non-protein
      calories did not differ significantly between the two patient groups. An average
      weight gain in group B contrasted with an average weight loss in group A after
      four (P < 0.01) and eight weeks (P < 0.05). Fat-free mass showed an intergroup
      difference in favor of group B after eight weeks (P < 0.05). Body cell mass was
      maintained throughout the study in group B, but declined significantly up to
      weeks 4 and 8 in group A (intergroup difference: P < 0.05 and 0.01,
      respectively). A decrease in the total lymphocyte count by 559 cells/mul occurred
      with the fat-enriched diet (P < 0.05). Several aspects of the quality of life
      were rated to be better in group B than in group A, although not all differences
      reached statistical significance. CONCLUSION: In patients with cancer, a high-fat
      diet may possibly support the maintenance of both body weight and body cell mass.
      However, monitoring the lymphocyte count is advisable.

PMID- 16416369
TI  - The influence of oral L-arginine on fracture healing: an animal study.
AB  - BACKGROUND: The known biological activities of nitric oxide suggest a role in
      bone healing. We hypothesized that L-arginine, a source of nitric oxide,
      expedites the healing process of stabilized diaphyseal defects. TYPE OF STUDY:
      Prospective blinded animal study. METHODS: Using a guinea-pig model, a 7 mm
      diaphyseal and periosteal defect was produced in the right femur and splinted
      intramedullary with a 1.4 mm K-wire. The guinea pigs (n = 44) were treated orally
      in three parallel groups: two treatment groups received high doses of L-arginine
      (one group for 2 weeks and the other for 4 weeks) and a control group received
      vehicle only. After four weeks, all animals were killed and both femora
      explanted. Radiological, histological, histomorphometric and mechanical
      evaluation was performed blinded. RESULTS: Radiographs showed significantly more
      healing in the treatment groups (2 weeks, 10/15; 4 weeks, 11/15) than in the
      control group (3/14). The mechanical energy necessary for femur failure was
      significantly higher in the 4-week treatment group than in the control group (P <
      0.05). Histology and histomorphometry showed significantly increased coverage of
      nonvascularized bone fragments with newly formed bone in the treatment groups (P
      < or = 0.05). The contralateral uninjured femora did not show significant
      differences between groups. CONCLUSIONS: Oral L-arginine expedites healing in
      stabilized diaphyseal defects in guinea pigs without detrimentally affecting
      uninjured counterparts.

PMID- 16416370
TI  - [Referral to the pediatric dialysis unit -- the earlier the better?].
AB  - Whereas recent research has demonstrated clear evidence for beneficial effects of
      early referral to the nephrologist in chronic renal insufficiency in adults, no
      such data exist for the pediatric population. In this study, we therefore
      correlated patient age and residual renal function at first presentation to a
      specialized pediatric nephrologist with the extent of secondary uremic
      complications and the further course of renal function. From March 2003 until
      March 2004, 43 children (34 boys, aged 10.1 +/- 6.3 yrs) with congenital-urologic
      (n = 26), congenital-nephrologic (n = 13) or acquired (n = 4) renal diseases had
      been followed for 3.9 yrs (14 days to 17.5 yrs) at the Kinderdialyse Wien, with a
      residual renal function of 35 +/- 20.5 ml/min/1.73 m(2) at first presentation.
      With regards to uremic secondary complications, the majority of children
      exhibited involvement of at least two systems at first presentation. Thereafter,
      children with congenital diseases who were referred to the specialized pediatric
      nephrology unit within the first year of live demonstrated a significantly better
      course of residual renal function (1.8% vs -0.7%, p = 0.034) than children who
      were referred later. These data confirm recent registry reports on chronic renal
      insufficiency in children. Only about a third of the children of our population
      were presented to a specialized pediatric nephrology center within their first
      year of life (despite a congenital disease in 90% of them). Thus, therapeutic
      interventions might be currently offered at a delayed time point in the majority
      of children.

PMID- 16416371
TI  - PAI-1 4G/5G insertion/deletion promoter polymorphism and microvascular
      complications in type 2 diabetes mellitus.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in
      the regulation of fibrinolysis and extracellular matrix turnover. PAI-1 4G/5G
      insertion/deletion polymorphism in the PAI-1 promoter region has been shown to
      modulate PAI-1 plasma levels. We investigated the relationship between this
      polymorphism and the prevalence of diabetic nephropathy and retinopathy in
      patients with type 2 diabetes in the Austrian population. PATIENTS AND METHODS:
      147 consecutive patients with type 2 diabetes mellitus (96 men, 51 women; median
      age, 65 years; IQR, 59-71) were analyzed for the PAI-1 4G/5G genotype. RESULTS:
      The genotype distribution in the individuals tested was as follows: 17% (n = 25)
      5G/5G, 54% (n = 80) 4G/5G, and 29% (n = 42) 4G/4G. Patients homozygous for allele
      4G had a significantly higher risk of diabetic proliferative retinopathy than
      patients without signs of diabetic retinopathy or nonproliferative retinopathy
      (OR, 7.3; 95% CI, 1.4-38.8; P = 0.02). No significant associations were observed
      between the PAI-1 genotype and the presence of albuminuria. CONCLUSION: According
      to our results, diabetic proliferative retinopathy might be associated with the
      prevalence of PAI-1 genotype 4G/4G.

PMID- 16416372
TI  - Color Doppler ultrasonography is reliable in assessing the risk of esophageal
      variceal bleeding in patients with liver cirrhosis.
AB  - PURPOSE: The aim of the study was to examine the role of Doppler ultrasonography
      of the portal vein in predicting esophageal variceal bleeding in patients with
      liver cirrhosis and portal hypertension by comparing the ultrasound data to the
      endoscopic findings. PATIENTS AND METHODS: 99 patients with liver cirrhosis and
      esophageal varices underwent color Doppler ultrasonography and
      esophagogastroduodenoscopy. The following portal hemodynamic parameters were
      analyzed: diameter and cross-sectional area, mean blood flow velocity, blood flow
      volume, perfusion pressure gradient, congestion index, and platelet count-to
      spleen diameter ratio. Variceal characteristics, the size and the presence of red
      signs, were determined by endoscopic examination. RESULTS: Patients with variceal
      red signs had significantly higher values of portal diameter (1.538 +/- 0.246 vs.
      1.243 +/- 0.167), cross-sectional area (1.286 +/- 0.448 vs. 0.945 +/- 0.256),
      blood flow volume (965.520 +/- 432.728 vs. 625.117 +/- 320.999) and congestion
      index (0.165 +/- 0.068 vs. 0.126 +/- 0.051) than patients without red signs,
      while the perfusion pressure gradient (0.260 +/- 0.087 vs. 0.447 +/- 0.271) and
      the platelet-to-spleen ratio (522.424 +/- 222.823 vs. 708.921 +/- 230.769) were
      lower. The same pattern of differences between the ultrasound parameters was
      found in patients with large varices comparing ones with red signs to the ones
      without them (diameter, 1.567 +/- 0.234 vs. 1.258 +/- 0.175; cross-section, 1.313
      +/- 0.455 vs. 1.061 +/- 0.264; flow volume, 988.195 +/- 443.353 vs. 739.423 +/-
      414.281; congestion index, 0.171 +/- 0.067 vs. 0.130 +/- 0.058; perfusion
      pressure gradient 0.247 +/- 0.078 vs. 0.501 +/- 0.379 and platelet-to-spleen
      ratio 479.930 +/- 184.302 vs. 699.094 +/- 316.171). Differences in values of
      ultrasonographic parameters were less obvious among groups of patients with
      different variceal sizes: only the diameter, cross-sectional area and blood flow
      volume were significantly different. The mean blood flow velocity did not depend
      on the variceal size or on the presence of red signs. The sensitivities and
      specificities of the analyzed parameters were 60-80% and 48.6-78.4%,
      respectively. CONCLUSIONS: Results suggest that color Doppler ultrasonography is
      a useful noninvasive method for evaluating the risk of esophageal variceal
      bleeding in patients with liver cirrhosis.

PMID- 16416373
TI  - Laryngocele in association with ankylosing spondylitis.
AB  - A laryngocele is a cystic dilatation of the laryngeal saccule. The etiology of
      laryngoceles is unclear, but congenital and acquired factors are considered to
      play a role in their development. An acquired laryngocele may develop when the
      laryngeal ventricle becomes functionally obstructed as a result of an increase in
      intraglottic pressure, such as that caused by excessive coughing, playing a wind
      instrument, glass blowing or obstruction of appendicular ostium. We present a
      case of laryngocele in a patient with ankylosing spondylitis. To the authors'
      knowledge, and from a review of the literature, this combination has not been
      previously described. The laryngocele was also infected in this case. We believe
      that development of the laryngocele might be a result of increased intra
      abdominal pressure, caused by rheumatoid arthritis, with associated increased
      intralaryngeal pressure.

PMID- 16416374
TI  - Surgical treatment of femoral bending deformity in a patient with vitamin D
      resistant rickets.
AB  - Surgical treatment of patients with vitamin D-resistant rickets is reserved for
      management of severe deformities or pathological fractures of the lower limbs.
      This case report describes the operative management of a child with vitamin D
      resistant rickets suffering from a pathological fracture and a bending deformity
      of the right femoral bone. A modified technique of fragmentation and realignment
      by intramedullary fixation was performed using an unreamed humerus nail. We
      corrected the anatomical proximal femoral shaft angle (aMPFA) from 68 degrees to
      84 degrees and achieved three more centimetres of femoral length. The same
      procedure was performed on the left femur and corrected the aMPFA from 108
      degrees to 89 degrees and gained 2.5 more centimetres of femoral length. Thus the
      legs were almost equal in length. We preferred the modified technique of multiple
      osteotomies and intramedullary fixation by nailing (originally described by
      Sofield and Millar) because the correction of angulation and rotation of the
      femoral shaft in one step appeared to be much easier than with plate fixation.
      Moreover, this method seems to reduce the number of refractures and enables the
      patients to approach the normal activities of growing children.

PMID- 16416378
TI  - [The classical parasite: from appreciative partners of the gods to serving as
      jesters].
AB  - A [pialpharhoalphasigmaiotatauomicronzeta] = parasitos = parasite of the
      classical Greek antiquity was a tolerated, but not invited co-eater during a
      guest meal. Usually a parasite was an illegitimate, incapable to inherit or
      anyway pauperised, free, young man who had to pay for his meal with exhilaration
      of the guests, adulation, maintenance art, and humiliation. However, during the
      more than two millennia lasting development of the classical antique society,
      even this little prestigious profession was preceded by a stupendous development,
      reflecting an unprecedented devaluation of this socially enforced activity. At
      the outset of the development there stood the archaic, neolithic social order of
      Greece, within which a parasitos was the selected partner of the divinity and at
      the same time a civil servant of a municipality and an outstanding citizen of a
      community. In the classical antiquity the term parasitos had a socio-political
      contents above all; the term incorporated itself into the ancient sacral, social,
      and constitutional spheres. The transformation to a medical word meaning took
      originally place in the course of an erroneous reception during the 17th century.

PMID- 16416379
TI  - [New vaccines for travelers].
AB  - The title "new vaccines" allows different approaches, such as the first option to
      vaccinate against a specific disease, new compositions and new ways of the
      application of vaccines, new target groups and indications, new combinations of
      compounds already on the market or new ways to trigger defense mechanisms. This
      article is focused on products that were recently launched in Austria: vaccines
      providing combined protection against hepatitis A and typhoid fever, a vaccine
      against cholera and ETEC (enterotoxigenic Escherichia coli) (in comparison to
      another cholera vaccine), vaccines against Japanese encephalitis and a conjugated
      vaccine against meningococcal disease (in comparison to a polysaccharide
      vaccine), respectively.

PMID- 16416380
TI  - [Travel vaccination recommendations for Central and Eastern European countries
      based on country-specific risk profiles].
AB  - Within the last years, an increasing trend of voyages to Central and Eastern
      European destinations could be observed. However, Europeans travelling within
      their own continent do not consider themselves as travellers exposed to possibly
      travel-associated infections since problem awareness among tourists as well as
      consulting doctors is rather scanty. The objective of this expert statement is to
      outline country-specific risk profiles as well as guidelines with regard to
      relevant travel immunizations for this region. These recommendations are mainly
      based on risk estimates according to national incidences and prevalences of
      vaccine-preventable diseases such as hepatitis A, hepatitis B, typhoid fever,
      meningococcal meningitis, rabies, and tick-borne encephalitis.

PMID- 16416381
TI  - [Toxoplasmosis round-robin test in Austria: results and limits of the
      toxoplasmosis screening].
AB  - In 1983 the Osterreichische Gesellschaft fur Qualitatssicherung und
      Standardisierung medizinisch-diagnostischer Untersuchungen (OQUASTA) has invited
      the Department of Medical Parasitology of the Clinical Institute of Hygiene and
      Medical Microbiology, University of Vienna (today: Medical University of Vienna),
      to establish an external quality assessment service on the detection of specific
      antibodies against Toxoplasma gondii, one of the most prevalent protozoic
      parasites in the world. The objective of this project was the support of Austrian
      laboratories in standardising their test methods for the detection of specific
      antibodies against T. gondii. Between 1983 and 2004, 45 collaborating studies
      were carried out. During this period, the number of participating laboratories
      has increased from 10 in 1983 to about 50 in recent years. In total, the test
      results produced by the laboratories matched with the nominal values in more than
      90%. On the examples of three human cases we demonstrate that externally
      validated serological methods alone, despite their great benefit, are not enough
      for a sufficient serodiagnosis of toxoplasmosis; unusually complicated
      serological situations do arise and can only be met by the knowledge about
      special tests, the application of an appropriate examination strategy and -- last
      but not least -- by many years of experience.

PMID- 16416382
TI  - Toxoplasmosis surveillance during pregnancy and quality assurance of methods in
      Hungary.
AB  - In Hungary, screening programs have been performed for the early detection of
      toxoplasmosis in pregnant women in three different counties. The results of a
      screening program performed in the town of Szeged are discussed in details. The
      pregnant women are screened by serological and molecular biological methods (anti
      Toxoplasma CFT, IgG, IgM, anti-P30 IgA ELISA, IgG avidity test, PCR
      amplification). The women are first screened within the first 16 weeks of
      gestation. Seronegative cases are retested for seroconversion in every second
      month. Appropriate treatment is immediately started both in the mothers
      suspicious of acute toxoplasmosis and in their offspring. The urine samples of
      the babies are examined by nested PCR specific to B1 gene of Toxoplasma gondii.
      No cases of congenital toxoplasmosis have been detected among the screened and
      treated children so far. Thus, we consider the program as highly successful for
      screening of congenital toxoplasmosis. To insure the quality of the applied
      laboratory diagnostic methods, the QualiCont Company organizes two quality
      control investigations yearly in the laboratories involved.

PMID- 16416383
TI  - Drug sensitivity of Plasmodium falciparum along the Thai-Myanmar border using the
      new field-deployable HRP2 in vitro assay.
AB  - Drug resistance in Plasmodium falciparum has turned into a major problem
      throughout the malaria endemic regions of the world. Surveillance of antimalarial
      drug resistance is therefore essential for early changes in drug policies. In the
      course of this first major application of the new field-deployable histidine-rich
      protein 2 (HRP2) in vitro drug sensitivity assay, we investigated the current
      status of drug sensitivity to the standard antimalarial drugs dihydroartemisinin,
      mefloquine, quinine, and chloroquine in an area with an exceptionally high level
      of multidrug resistance in Thailand. The geometric mean of 50 and 90% inhibitory
      concentrations determined for 44 successfully tested samples by the HRP2 assay
      were comparable to earlier published results from the same area suggesting
      relatively little change in the local drug resistance pattern during the past
      years. The HRP2 field test was found to be highly sensitive and simple enough to
      be entirely performed in the field.

PMID- 16416384
TI  - Synergism of desbutyl-benflumetol and retinol against Plasmodium falciparum in
      vitro.
AB  - This in vitro study was conducted to assess the blood schizontocidal activity of
      desbutyl-benflumetol (DBB), a new benzindene derivative, retinol and a
      combination of both compounds. The tests were carried out according to the
      methodology of the WHO standard test Mark II, measuring the drug-dependent
      inhibition of schizont maturation, and using 43 fresh isolates of Plasmodium
      falciparum from northwestern Thailand, an area with established multidrug
      resistance. DBB and retinol showed a mean 50% effective concentration (EC-50) of
      3.73 nM and 466.86 nM and 90% effective concentration (EC-90) of 19.83 nM and
      5531.69 nM respectively. The combination of DBB and 3.50 muM retinol showed
      strong inhibition of schizont maturation, with an EC-90 for DBB of 0.67 nM. At
      the therapeutically relevant EC-99, the combination was about 10 times more
      effective than expected, suggesting that retinol potentiated the effect of DBB. A
      concentration of 3.50 muM retinol corresponds to the 95th percentile of the
      physiological serum levels. It is well known that retinol levels are
      significantly decreased in acute falciparum malaria. Supplementation with retinol
      during malaria treatment may improve the therapeutic results of blood
      schizontocides of the fluorene class.

PMID- 16416385
TI  - In vitro activity of artemisinin alone and in combination with retinol against
      Plasmodium falciparum.
AB  - Increasing resistance of Plasmodium falciparum to antimalarial drugs is an
      important public health problem, demanding novel therapeutic approaches. This
      study had the objective of assessing the in vitro activity of artemisinin and its
      combination with retinol in fresh isolates of P. falciparum in an area with a
      high proportion of multidrug-resistant strains. The tests were based on the
      inhibition of schizont maturation. In 45 successfully tested isolates, the mean
      effective concentrations (ECs) of artemisinin were 10.29 nM for the EC-50 and
      34.86 nM for the EC-90. The EC50 and EC90 for artemisinin in the artemisinin
      retinol mixture were 2.71 nM and 13.37 nM, respectively. The combination showed
      synergistic activity. Retinol appears to be a promising partner for the
      antimalarial therapy with artemisinins.

PMID- 16416387
TI  - [Holiday dreams with a downside: uncommon tapeworm infection in an infant].
AB  - Eight weeks after his return from Mauritius, a 2.5-year-old boy started to show
      signs of gastrointestinal illness including diarrhoea with frequent ill-smelling
      stools as well as restlessness, insomnia and apathy. Proglottids excreted with
      the faeces were diagnosed as Raillietina madagascariensis (Davain, 1870), the
      tropical rat tapeworm. Treatment with praziquantel (10 mg/kg BW) proved to be
      efficient.

PMID- 16416386
TI  - Clinical features, aetiology and short-term outcome of interstitial pneumonitis
      in HIV/AIDS patients at Bamrasnaradura Hospital, Nonthaburi, Thailand.
AB  - This prospective study was conducted at Bamrasnaradura Hospital from November 11,
      2002, until January 5, 2003, in order to describe the clinical manifestations and
      determine the aetiologies as well as to assess the short-term outcome of
      interstitial pneumonitis in HIV/AIDS patients. 59 patients with interstitial
      infiltrates on chest radiographs were included in the study. Tuberculosis (TB)
      was the most common diagnosis (44%), followed by Pneumocystis pneumonia (PCP)
      (25.4%), bacterial pneumonia (20.3%) and fungal pneumonia (10.2%). In TB,
      compared to other diagnoses, a mild cough (p = 0.031), pallor (p = 0.021),
      lymphadenopathy (p < 0.001), an absence of skin lesions (p = 0.003), a higher
      mean body temperature (p = 0.004) and an absence of dyspnoea on exertion (p =
      0.042) were significant findings. In PCP, compared to other diagnoses, dyspnoea
      on exertion (p = 0.014), nonpurulent sputum production (p = 0.047), a higher mean
      respiratory rate (p < 0.001), and an absence of lymphadenopathy (p < 0.001) were
      significant factors. In bacterial pneumonia, compared to other diagnoses,
      production of purulent sputum (p = 0.014), haemoptysis (p = 0.006), skin lesions
      (p = 0.002) and severe cough (p = 0.040) were significantly associated factors.
      In fungal pneumonia, compared to other diagnoses, headache and papulonecrotic
      skin lesions were common findings, but no factor showed a significant
      association. After four weeks, 59.3% patients were alive and 13.6% had died.
      Among those alive, 88.6% had clinically improved. The cumulative survival after
      28 days was highest among PCP patients, followed by bacterial pneumonia, TB and
      fungal pneumonia, but these differences were statistically not significant (p =
      0.453).

PMID- 16416388
TI  - Neurodegeneration and oxidative stress: prion disease results from loss of
      antioxidant defence.
AB  - Prion diseases or transmissible spongiform encephalopathies (TSEs) are rare
      neurodegenerative disorders that can be acquired either by direct transmission,
      inherited through dominant mutations in the prion protein gene or via an unknown
      sporadic cause. This latter group constitutes the vast majority of cases. Like
      many neurodegenerative diseases the hallmarks of oxidative damage can be readily
      detected throughout the brain of the affected individual. However, unlike most
      other neurodegenerative diseases, prion diseases are connected with a dramatic
      loss of antioxidant defence. As abnormal protein accumulates in the diseased
      brain there is both an increase of oxidative substances and a loss of the
      defences that keep them in check. In particular the normal cellular prion protein
      has been shown to be an antioxidant. Conversion of this protein to the protease
      resistant isoform is accompanied by a loss of this antioxidant activity. This
      change creates a paradox as the loss of activity is not accompanied by a loss of
      protein expression. It is likely that this prevents other cellular defences from
      responding sufficiently to protect neurons from the heightened oxidative burden.
      Recent experiments with transgenic mice have shown that when prion protein
      expression is switched off during the course of prion disease, cell death is
      dramatically halted and the mouse recovers from the disease. This result clearly
      illustrates that the continued expression of non-function prion protein is
      essential for disease progression. This implies that the presence of this
      abnormal protein during prion disease causes a failure of cellular antioxidant
      defence. This failed defence is the fundamental cause of the massive
      neurodegeneration that results in the fatal nature of TSEs. The role of oxidative
      stress in TSEs and other neurodegenerative disorders are discussed in this
      review.

PMID- 16416389
TI  - Tauopathies: recent insights into old diseases.
AB  - Neurofibrillary tangles are brain lesions that have been discovered at the
      beginning of the 20th century, using histological silver staining. Tangles are
      intra-neuronal hallmarks of a degenerating process: neurofibrillary degeneration
      (NFD). The basic component involved in tangle formation is tau protein. Tangles
      are found in more than 20 different neurodegenerative disorders, suggesting that
      NFD is a unique consequence to different types of etiological factors. However,
      tangles have a morphological and biochemical signature which is disease-specific.
      They are made up of different types of filaments such as paired helical filaments
      (PHFs) in Alzheimer's disease or straight filaments in progressive supranuclear
      palsy. Tau aggregates have a disease-specific biochemical bar-code due to the
      aggregation of specific sets of tau isoforms. Tau lesions have also a disease
      specific pattern of spatio-temporal progression in the human brain which is well
      correlated to cognitive impairment. At last, pathological tau mutations are at
      the origin of familial fronto-temporal diseases with parkinsonism (FTDP-17).
      Together, these observations have generated the concept of tauopathies. Indeed,
      each tauopathy is defined by a combination of clinical, neuropathological,
      biochemical and genetic features. Most of them have a specific defect on tau
      (mutation, aberrant splicing, abnormal phosphorylation, abnormal processing,
      neuronal or genotypic vulnerability), suggesting that, in fact, the etiology of
      most tauopathies is directly linked to tau dysfunction. In conclusion, we observe
      that most dementing disorders are tauopathies and that most demented patients
      have a tauopathy.

PMID- 16416390
TI  - Frontotemporal dementia and parkinsonism linked to chromosome 17.
AB  - Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an
      autosomal dominant neurodegenerative disorder caused by mutations in the MAPT
      gene which encodes the microtubule-associated protein tau. This hereditary
      tauopathy is a rare clinical syndrome, affecting approximately two hundred
      kindreds and about six hundred individuals bearing thirty nine known MAPT
      mutations. The disorder is thought to be related to the altered proportion of tau
      protein isoforms or the ability of tau to bind to microtubules and to promote
      microtubule assembly and organization. The clinical presentation of FTDP-17
      includes behavioral, cognitive and motor abnormalities. This disorder has both a
      variable course and phenotype. Gross neuropathological examination reveals brain
      atrophy, especially of the frontal and temporal lobes, and selective atrophy of
      the basal ganglia and brainstem nuclei. The major microscopic features of FTDP-17
      demonstrate the presence of neurofibrillary tangles, neuropil threads and glial
      inclusions composed of insoluble tau protein. Distribution and amount of tau
      deposits vary, depending on the type of MAPT mutation. The definitive diagnosis
      of FTDP-17 requires a set of clinical and pathological features combined with a
      molecular genetic analysis. Currently, there is no known effective treatment for
      FTDP-17.

PMID- 16416391
TI  - Risks of transmission of variant Creutzfeldt-Jakob disease by blood transfusion.
AB  - Variant Creutzfeldt-Jakob disease (vCJD) was first identified in 1996 in the UK,
      and results from human exposure to the bovine spongiform encephalopathy (BSE)
      agent. vCJD has subsequently been identified in 10 additional countries, and
      numbers continue to increase in the UK. Unlike other human prion diseases,
      infectivity and the disease-associated form of the prion protein are readily
      detected in lymphoid tissues in vCJD. In experimental BSE infection in a sheep
      model, infectivity has been transmitted by blood transfusion from asymptomatic
      infected animals to normal recipient animals, indicating that infectivity is
      present in blood during the incubation period. Recently, two cases of apparent
      iatrogenic vCJD infection by blood transfusion from asymptomatic donors who
      subsequently died from vCJD have been reported from the UK. The first case
      resulted in clinical illness identical to other cases of vCJD, while the second
      case was an asymptomatic infection detected at autopsy. Sensitive means of
      detection of disease-associated prion protein in the blood are required in order
      to be employed for screening purposes, both individually at the time of blood
      donation, and to help ascertain future numbers of vCJD cases in the UK and
      beyond.

PMID- 16416392
TI  - Creutzfeldt-Jakob disease in Hungary.
AB  - Human prion diseases or transmissible spongiform encephalopathies are progressive
      fatal neuropsychiatric diseases. In addition to the evaluation of clinical
      features, a common diagnostic procedure includes examination of the protein 14-3
      3 in the cerebrospinal fluid, performing EEG to detect periodic sharp wave
      complexes with triphasic morphology, and cranial MRI to demonstrate high signal
      intensity in the basal ganglia or thalamus. The definite diagnosis requires a
      neuropathological examination. The analysis of the prion protein gene (PRNP) is
      initiated mainly after suspicion of a positive family history or an atypical
      presentation. In Hungary collecting data and setting up the neuropathological
      diagnosis in suspect prion disease cases originates from the late 1960s.
      Systematic surveillance was established in 1994 and since 2001 reporting of
      Creutzfeldt-Jakob disease has been compulsory. According to our database, the
      incidence of genetic prion disease is increased in Hungary. The most frequent
      mutation in the PRNP is at codon 200. This might be linked to migration from the
      Slovakian focus. Acquired forms of prion disease were not detected in our
      country. The surveillance system is based on referrals from clinicians and
      pathologists and the aim is to perform the neuropathological examination and
      analysis of the PRNP on the majority of suspect cases.

PMID- 16416394
TI  - Autophagy--a basic mechanism and a potential role for neurodegeneration.
AB  - Autophagy constitutes a fundamental survival strategy of cells; its disturbance
      contributes to the pathogenesis of cancer, liver and immune disease, pathogen
      infection, myopathies as well as neurodegenerative disorders such as Amyotrophic
      lateral sclerosis, Parkinson;s, Huntington;s and Alzheimer;s disease. The
      pathogenesis of neurodegenerative diseases also involves a gradual and
      progressive loss of neuronal cells. Cells may use different pathways for active
      self-destruction as reflected by different morphology: while in apoptosis (or
      "type I") nuclear fragmentation associated with cytoplasmic condensation but
      preservation of organelles is predominant, autophagic degradation of the
      cytoplasmic structures preceding nuclear collapse is a characteristic of a second
      type of programmed cell death (PCD). Linking autophagy to programmed cell death
      initiated a controversial discussion on how a suggested role of autophagy in cell
      suicide might meet with its established survival function. To some extent, the
      diverse morphologies can be associated with distinct biochemical and molecular
      events [caspase-dependent and -independent death programs, DAP-kinase activity,
      Ras-expression, induction of autophagy genes, fate of cytoskeleton, among
      others]. However, there is a broad overlap between cell death pathways.
      Conceivably, diverse PCD programs emerged during evolution, the conservation of
      which allows eukaryotic cells a flexible response to physiological or
      pathological demands.

PMID- 16416395
TI  - Microglial cells in neurodegenerative disorders.
AB  - Microglia are resident immune cells of the CNS. They are involved in the
      pathogenesis of diverse neurodegenerative diseases such as Alzheimer's disease,
      Parkinson's disease, prion diseases as well as multiple sclerosis, amyotrophic
      lateral sclerosis and AIDS dementia complex. It is widely accepted that microglia
      contribute to the neurodegeneration through a release of a variety of
      proinflammatory substances. In fact, they are not the only cells which contribute
      to immunological processes inside the nervous system. The CNS is composed of
      different cell populations that answer to pathological factors and influence each
      other and modulate their reactions. These complex interactions are responsible
      for the development of brain pathology. This paper reviews the available
      information on microglial cells contribution to AD, PD and prion diseases
      development.

PMID- 16416393
TI  - Neurodegeneration with brain iron accumulation.
AB  - Neurodegeneration with brain iron accumulation (NBIA) describes a group of
      progressive extrapyramidal disorders with radiographic evidence of focal iron
      accumulation in the brain, usually in the basal ganglia. Patients previously
      diagnosed with Hallervorden-Spatz syndrome fall into this category. Mutations in
      the PANK2 gene account for the majority of NBIA cases and cause an autosomal
      recessive inborn error of coenzyme A metabolism called pantothenate kinase
      associated neurodegeneration (PKAN). PKAN is characterized by dystonia and
      pigmentary retinopathy in children or speech and neuropsychiatric disorders in
      adults. In addition, a specific pattern on brain MRI, called the eye-of-the-tiger
      sign, is virtually pathognomonic for the disease. Pantothenate kinase is
      essential to coenzyme A biosynthesis, and the PANK2 protein is targeted to the
      mitochondria. Hypotheses of PKAN pathogenesis are based on the predictions of
      tissue-specific coenzyme A deficiency and the accumulation of cysteine-containing
      substrates. Identification of the major NBIA gene has led to more accurate
      clinical delineation of the diseases that comprise this group, a molecular
      diagnostic test for PKAN, and hypotheses for treatment.

PMID- 16416396
TI  - The role of excitotoxicity in neurodegeneration.
AB  - A body of evidence suggests that the mechanisms of excitotoxic neuronal damage
      evoked by excessive or prolonged activation of the excitatory amino acid
      receptors may be involved in pathogenesis of brain damage in acute insults and in
      chronic neurodegenerative diseases. In this review we briefly discuss several
      selected mechanisms of the excitotoxicity, focusing attention on the role of
      ionotropic glutamate receptors, calcium transients and calcium-mediated cell
      injury. In the second part of this paper we provide information on elements of
      excitotoxicity in brain diseases.

PMID- 16416397
TI  - Short-term treatment with rivastigmine and plasma levels of Abeta peptides in
      Alzheimer's disease.
AB  - Deregulation of APP metabolism is considered to be a key pathogenic event in
      Alzheimer's disease. Data from cell cultures indicate that the secretion of
      Abeta1-42 might be inhibited by cholinesterase inhibitors, possibly via M1
      receptors stimulation. Treatment with tacrine, a dual acetyl- and
      butyrylcholinesterase inhibitor, had no significant effect on mean plasma Abeta
      species concentrations. However, a correlation was observed between higher drug
      concentrations and lower Abeta levels that might indicate an effect on APP
      metabolism with an increased alpha-cleavage. Abeta1-40 and Abeta1-42 levels were
      measured in the plasma of 28 AD subjects by means of a commercially available
      ELISA before rivastigmine treatment and at week 2 after the first dose of the
      drug (3 mg/day) had been administered. Treatment with rivastigmine exhibited a
      significant effect on mean plasma concentrations of Abeta1-42 (mean difference
      7.8+/-8.4, t=-4.9, pmean difference 7.8+/-8.4, t=-4.9, p<0.001) with a negative
      correlation with the patients age (Pearson's R=-0.40, p=0.035). No significant
      effect on plasma Abeta1-40 was observed. The observed increase of mean levels of
      plasma Abeta1-42 after rivastigmine treatment might indicate an effect of the
      drug on Abeta metabolism, mobilization of Abeta1-42 from deposits in the affected
      brain areas and a consecutive Ab1-42 brain-to-plasma efflux. The negative
      correlation between Abeta1-42 plasma levels changes and age may be a sign of
      impairment of this process in the older patients. A large individual variation of
      the observed response, however, excludes drawing definite conclusions. Whether
      those subjects who respond to rivastigmine in terms of Abeta1-42 plasma levels
      changes also respond clinically needs to be established.

PMID- 16416398
TI  - Sneddon's syndrome as a disorder of small arteries with endothelial cells
      proliferation: ultrastructural and neuroimaging study.
AB  - We report a 18-year-old female patient with livedo reticularis and neurological
      disturbances. CT scan showed two big ischemic focuses in the pons, moreover MRI
      revealed small disseminated ischemic focuses in the pons and deep structures of
      both brain hemispheres. MRA demonstrated no changes in the big extracranial and
      intracranial arteries. Since the clinical data and neuroimaging results suggested
      Sneddon's syndrome, the skin and skeletal muscle biopsy was taken to examine. The
      immunohistochemical and ultrastructural investigations of the skin biopsy
      revealed a significant reduction of the lumen of the capillaries and small to
      medium-sized arteries. Cells surrounding the vascular lumen, frequently with
      multilayer arrangement and their nuclei placed perpendicularly to the lumen, were
      CD31, CD34, and sporadically SMA positive. At the ultrastructural level, these
      proliferating cells showed typical features of endothelial cells: abundant
      intermediate filaments and Weibel-Palade bodies. Between the endothelial cells
      some junctions were detached as well in the capillaries as in the small arteries.
      The smooth muscle cells of the small arteries were electron denser than usual and
      their cytoplasmic protrusions penetrated to the endothelial cells. The
      ultrastructural picture of some vessels with a considerably narrow lumen was
      typical of vessels newly formed during angiogenesis. Neuroimaging including TC,
      MRI, MRA besides histological, immunohistochemical and ultrastructural evaluation
      may be useful for diagnosis of Sneddon's syndrome.

PMID- 16416401
TI  - A dynamic model for estimating changes in health status and costs.
AB  - We develop an innovative method to assess total treatment costs over a finite
      period of time while incorporating the dynamics of change in the health status of
      patients. Costs are incurred through medical care use while patients sojourn in
      health states. Because complete ascertainment of costs and observation of events
      are not always feasible, some patient utilization will be incomplete and events
      will also be censored. A Markov model is used to estimate the transition
      probabilities between health states and the impact of patient variables on
      transition intensities. A mixed-effects model is used for sojourn costs with
      transition times as random effects and patient variables as fixed effects. The
      models are combined to estimate net present values (NPVs) of expenditures over a
      finite time interval as a function of patient characteristics. The method is
      applied to a data set of 624 incident cases of cancer. Physical functioning after
      cancer diagnosis was assessed periodically through structured interviews. The
      outcomes of interest are normal physical function, impaired physical function, or
      the terminal state, dead. Charges were obtained from Medicare claim files for 2
      years following cancer diagnosis. For demonstration purposes, we estimate NPVs
      for charges incurred over 2 years by cancer site and cancer stage. Our method, a
      joint regression model, provides a flexible approach to assessing the influence
      of patient characteristics on both cost and health outcomes while accommodating
      heteroscedasticity, skewness and censoring in the data.

PMID- 16416402
TI  - Intraclass correlation coefficients and bootstrap methods of hierarchical binary
      outcomes.
AB  - Intraclass correlation coefficients are designed to assess consistency or
      conformity between two or more quantitative measurements. When multistage cluster
      sampling is implemented, no methods are readily available to estimate intraclass
      correlations of binomial-distributed outcomes within a cluster. Because
      statistical distribution of the intraclass correlation coefficients could be
      complicated or unspecified, we propose using a bootstrap method to estimate the
      standard error and confidence interval within the framework of a multilevel
      generalized linear model. We compared the results derived from a parametric
      bootstrap method with those from a non-parametric bootstrap method and found that
      the non-parametric method is more robust. For non-parametric bootstrap sampling,
      we showed that the effectiveness of sampling on the highest level is greater than
      that on lower levels; to illustrate the effectiveness, we analyse survey data in
      China and do simulation studies.

PMID- 16416403
TI  - Bayesian semi-parametric ROC analysis.
AB  - This paper describes a semi-parametric Bayesian approach for estimating receiver
      operating characteristic (ROC) curves based on mixtures of Dirichlet process
      priors (MDP). We address difficulties in modelling the underlying distribution of
      screening scores due to non-normality that may lead to incorrect choices of
      diagnostic cut-offs and unreliable estimates of prevalence of the disease. MDP is
      a robust tool for modelling non-standard diagnostic distributions associated with
      imperfect classification of an underlying diseased population, for example, when
      a diagnostic test is not a gold standard. For posterior computations, we propose
      an efficient Gibbs sampling framework based on a finite-dimensional approximation
      to MDP. We show, using both simulated and real data sets, that MDP modelling for
      ROC curve estimation closely parallels the frequentist kernel density estimation
      (KDE) approach.

PMID- 16416404
TI  - Folding with downhill behavior and low cooperativity of proteins.
AB  - The downhill folding observed experimentally for a small protein BBL is studied
      using off-lattice Go-like model. Our simulations show that the downhill folding
      has low cooperativity and is barrierless, which is consistent with the
      experimental findings. As an example of comparison in detail, the two-state
      folding behavior of proteins, for example, protein CI2, is also simulated. By
      observing the formation of contacts between the residues for these two proteins,
      it is found that the physical origin of the downhill folding is due to the
      deficiency of nonlocal contacts which determine the folding cooperatively. From a
      statistics on contacts of the native structures of 17 well-studied proteins and
      the calculation of their cooperativity factors kappa2 based on folding
      simulations, a strong correlation between the number of nonlocal contacts per
      residue NN and the factors kappa2 is obtained. Protein BBL with a value of NN =
      0.73 has the lowest cooperativity factor kappa2 = 0.34 among all 17 proteins. A
      crossover around NNc approximately 0.9 could be defined to separate the two-state
      folders and the downhill folder roughly. A protein would behave downhill folding
      when its NN = NNc. For proteins with their NN values are about (or slightly
      larger than) NNc, the folding behaves with low cooperativity and the barriers are
      small, showing a weak two-state behavior or a downhill-like behavior.
      Furthermore, simulations on mutants of a two-state folder show that a mutant
      becomes a downhill folder when its NN is reduced to a value smaller than NNc.
      These could enable us to identify the downhill folding or the cooperative two
      state folding behavior solely from the native structures of proteins.

PMID- 16416405
TI  - Some indicators of socio-economic status may not be reliable and use of indices
      with these data could worsen equity.
AB  - Socio-economic status (SES) indices are increasingly being used to characterise
      (in)equity, with the assumption that SES indices are reliable. However, the
      accuracy of such SES indices is questionable if they are unreliable. We examined
      the inter-rater and test-retest reliability of a range of indicators commonly
      used to generate SES indices as well as the composite SES indices. Results from
      research in southeast Nigeria showed considerable variation, with some indicators
      having only low to moderate reliability (reliability coefficients 0.25-0.77).
      Inter-rater and test-retest reliability of SES indices was 0.63 in both cases.
      Many households were misclassified because of the unreliable SES indices.
      Analyses of the distribution of resources based on such indicators could lead to
      inaccuracies in benefit incidence estimates and policy decisions based on low to
      moderately reliable SES indicators could worsen equity in access to and use of
      resources. Greater rigour is needed in conceptualising as well as undertaking SES
      measurements.

PMID- 16416406
TI  - Assessing genetic effects in survival data by correlating martingale residuals
      with an application to age at onset of Huntington disease.
AB  - Genetic models for survival data are hard to formulate and hard to fit. For
      example, the popular gamma-frailty model for sib-pair data does not generalize
      easily to extended pedigrees and is not easy to fit. In this paper we show how
      martingale residuals from a (marginal) Cox model can be employed to estimate the
      presence of a genetic effect and to estimate genetic correlations depending on
      the genetic distance (kinship). The methodology is applied to age at onset of
      Huntington disease (HD) in carriers of the HD gene. The number of CAG repeats in
      the HD gene is a well-known predictor for age at onset of the disease. However,
      there is an indication that other genes might be involved as well; leading to
      unexplained familial clustering. Using our methodology, we found a clearly
      significant genetic association between the martingale residuals with
      correlations of about 0.6 for relatives that share 50 per cent of their genes
      (sib-pairs and parent-child) and about 0.3 for relatives that share 25 per cent
      of their genes (grandparent-grandchild, uncle/aunt-niece/nephew).

PMID- 16416399
TI  - Deciphering the ancient and complex evolutionary history of human arylamine N
      acetyltransferase genes.
AB  - The human N-acetyltransferase genes NAT1 and NAT2 encode two phase-II enzymes
      that metabolize various drugs and carcinogens. Functional variability at these
      genes has been associated with adverse drug reactions and cancer susceptibility.
      Mutations in NAT2 leading to the so-called slow-acetylation phenotype reach high
      frequencies worldwide, which questions the significance of altered acetylation in
      human adaptation. To investigate the role of population history and natural
      selection in shaping NATs variation, we characterized genetic diversity through
      the resequencing and genotyping of NAT1, NAT2, and the pseudogene NATP in a
      collection of 13 different populations with distinct ethnic backgrounds and
      demographic pasts. This combined study design allowed us to define a detailed map
      of linkage disequilibrium of the NATs region as well as to perform a number of
      sequence-based neutrality tests and the long-range haplotype (LRH) test. Our data
      revealed distinctive patterns of variability for the two genes: the reduced
      diversity observed at NAT1 is consistent with the action of purifying selection,
      whereas NAT2 functional variation contributes to high levels of diversity. In
      addition, the LRH test identified a particular NAT2 haplotype (NAT2*5B) under
      recent positive selection in western/central Eurasians. This haplotype harbors
      the mutation 341T-->C and encodes the "slowest-acetylator" NAT2 enzyme,
      suggesting a general selective advantage for the slow-acetylator phenotype.
      Interestingly, the NAT2*5B haplotype, which seems to have conferred a selective
      advantage during the past approximately 6,500 years, exhibits today the strongest
      association with susceptibility to bladder cancer and adverse drug reactions. On
      the whole, the patterns observed for NAT2 well illustrate how geographically and
      temporally fluctuating xenobiotic environments may have influenced not only our
      genome variability but also our present-day susceptibility to disease.

PMID- 16416407
TI  - NADPH-diaphorase activity in the superficial layers of the superior colliculus of
      rats during aging.
AB  - Neurons in the superficial layers of the superior colliculus are key elements in
      the visual system of rodents since they receive extensive afferent projections
      from retinal ganglion cells. The NADPH-diaphorase histochemical technique was
      used to detect differences in neuronal nitric oxide synthase (nNOS) in the
      superficial layers of the superior colliculus (sSC) of young adult (3 months) and
      aged (24 and 26 months) rats. The orientation of the dendritic processes of NADPH
      diaphorase-positive neurons, cross-sectional area, and number of neurons per mm2
      were analyzed. NADPH-d histochemistry revealed a high number of NADPH-d-positive
      cells in the stratum zonale and stratum griseum superficiale in adult and aged
      animals. NADPH-d-positive neurons were classified into the following
      morphological types: marginal, horizontal, pyriform, narrow-field vertical, wide
      field vertical, and stellate. During aging, narrow field vertical and wide field
      vertical neurons present somatic atrophy and an increase in dendritic processes
      with dorsoventral orientation, whereas wide field vertical neurons show a
      decrease in those with lateromedial orientation. Marginal neurons undergo somatic
      hypertrophy at 26 months when compared with those at 3 months. The remaining
      types of neurons do not undergo size changes. Finally, the number of NADPH-d
      positive neurons per mm2 in the various types of morphology does not
      significantly change with age. It is suggested to be likely that the aging
      process in the nitrergic neurons of the sSC does not lead to significant changes
      in the synthesis of NO from the constitutive NOS isoforms.

PMID- 16416408
TI  - Effects of aging and HIF-1alpha deficiency on permeability of hippocampal
      vessels.
AB  - We examined age-related changes in the blood-brain barrier (BBB) of neural cell
      specific hypoxia inducible factor-1alpha (HIF-1alpha) deficient mice, which
      showed hydrocephalus with neuronal cell loss, to investigate an effect of neural
      cell-specific HIF-1alpha deficiency or hydrocephalus on vascular function.
      Vascular permeability of horseradish peroxidase (HRP) and binding of cationized
      ferritin (CF) particles to the endothelial cell luminal surface, as a marker of
      glycocalyx, were investigated. The thickness of CF-labeled glycocalyx was
      significantly decreased in the cortex in mutant mice compared with that of
      control mice, although it was not paralleled by increased vascular permeability.
      In addition, strong staining for HRP was seen around vessels located along the
      hippocampal fissure in 24-month-old mutant mice. The reaction product of HRP
      appeared in an increasing number of the endothelial cell abluminal vesicles and
      within the thickened basal lamina of arterioles in the hippocampus, showing
      increased vascular permeability. There were no leaky vessels in 10-week-old
      mutant mice or 10-week-old and 24-month-old control mice. These findings suggest
      the necessity of two factors, aging and hydrocephalus, for BBB dysfunction in HIF
      1alpha deficient mice.

PMID- 16416409
TI  - Image adaptive point-spread function estimation and deconvolution for in vivo
      confocal microscopy.
AB  - Visualizing deep inside the tissue of a thick biological sample often poses
      severe constraints on image conditions. Standard restoration techniques
      (denoising and deconvolution) can then be very useful, allowing one to increase
      the signal-to-noise ratio and the resolution of the images. In this paper, we
      consider the problem of obtaining a good determination of the point-spread
      function (PSF) of a confocal microscope, a prerequisite for applying
      deconvolution to three-dimensional image stacks acquired with this system.
      Because of scattering and optical distortion induced by the sample, the PSF has
      to be acquired anew for each experiment. To tackle this problem, we used a
      screening approach to estimate the PSF adaptively and automatically from the
      images. Small PSF-like structures were detected in the images, and a theoretical
      PSF model reshaped to match the geometric characteristics of these structures. We
      used numerical experiments to quantify the sensitivity of our detection method,
      and we demonstrated its usefulness by deconvolving images of the hearing organ
      acquired in vitro and in vivo.

PMID- 16416410
TI  - Arrangement and fine structure of collagen fibrils in the decidualized mouse
      endometrium.
AB  - The adaptations of the mouse uterus to pregnancy include extensive modifications
      of the cells and extracellular matrix of the endometrial connective tissue that
      surround the embryos. Around each implanted embryo this tissue redifferentiates
      into a transient structure called decidua, which is formed by polygonal cells
      joined by intercellular junctions. In the mouse, thick collagen fibrils with
      irregular profile appear in decidualized areas of the endometrium but not in the
      nondecidualized stroma and interimplantation sites. The fine organization of
      these thick fibrils has not yet been established. This work was addressed to
      understand the arrangement and fine structure of collagen fibrils of the decidua
      of pregnant mice during the periimplantation stage. Major modifications occurred
      in collagen fibrils that surrounded decidual cells: (1) the fibrils, which were
      arranged in parallel bundles in nonpregnant animals, became organized as baskets
      around decidual cells; (2) very thick collagen fibrils with very irregular
      profiles appeared around decidual cells. Analysis of replicas and serial sections
      suggests that the thick collagen fibrils form by the lateral aggregation of
      thinner fibrils to a central fibril resulting in very irregular profile observed
      in cross sections of thick fibrils. The sum of modifications of the collagen
      fibrils seem to represent an adaptation of the endometrium to better support the
      decidual cells while they hold the embryos during the beginning of their
      development. The deposition of thick collagen fibrils in the decidua may
      contribute to form a barrier that impedes leukocyte migration within the decidua,
      preventing immunological rejection of genetically dissimilar embryonic tissues.

PMID- 16416411
TI  - Compression of fluorescence microscopy images based on the signal-to-noise
      estimation.
AB  - Modern microscopic techniques like high-content screening (HCS), high-throughput
      screening, 4D imaging, and multispectral imaging may involve collection of
      thousands of images per experiment. Efficient image-compression techniques are
      indispensable to manage these vast amounts of data. This goal is frequently
      achieved using lossy compression algorithms such as JPEG and JPEG2000. However,
      these algorithms are optimized to preserve visual quality but not necessarily the
      integrity of the scientific data, which are often analyzed in an automated
      manner. Here, we propose three observer-independent compression algorithms,
      designed to preserve information contained in the images. These algorithms were
      constructed using signal-to-noise ratio (SNR) computed from a single image as a
      quality measure to establish which image components may be discarded. The
      compression efficiency was measured as a function of image brightness and SNR.
      The alterations introduced by compression in biological images were estimated
      using brightness histograms (earth's mover distance (EMD) algorithm) and textures
      (Haralick parameters). Furthermore, a microscope test pattern was used to assess
      the effect of compression on the effective resolution of microscope images.

PMID- 16416412
TI  - Dynamic-SIMS imaging and quantification of inorganic ions in frozen-hydrated
      plant samples.
AB  - We present here SIMS images of the distribution of inorganic cations (Na, K, Mg
      and Ca) in frozen-hydrated samples of three plant species, ivy, camomile, and
      flax. The samples were cryofixed using fast plunge-freezing. Stigmatic images
      were obtained, at 100 K, under dynamic SIMS conditions by fast atom bombarding
      (FAB). Even though the images obtained with the frozen-hydrated plant samples are
      still not of upper quality, they show that the method used to prepare these
      samples preserves existing ionic gradients between the outer and the inner part
      of the cells, between adjacent cells, including cells with the same type of
      differentiation, and between tissues. We also describe the quantification of the
      relative proportions of the ions in the vacuoles of flax. The reasonable accuracy
      achieved for quantification of the vacuole ion ratios permitted to show (i) that
      radial gradients of ion ratios in hypocotyls change when the plant is becoming
      older and (ii) that large differences may exist between adjacent cortical cells
      of the same type. The role of these substantial differences in vacuole ion
      balance ratios is a largely unexplored issue in plant physiology.

PMID- 16416414
TI  - A unique case of reversible hyperglycemic Holmes' tremor.
AB  - Various movement disorders are known manifestations of nonketotic hyperglycemia
      (NKH). Hyperglycemic tremors are rare, with only two cases resembling flapping
      tremors reported in literature. We present a unique case of reversible
      hyperglycemic Holmes' tremor associated with NKH and postulate the underlying
      pathophysiology of this condition.

PMID- 16416413
TI  - A discrete-state discrete-time model using indirect observation.
AB  - This research was motivated by a desire to model the progression of a chronic
      disease through various disease stages when data are not available to directly
      estimate all the transition parameters in the model. This is a common occurrence
      when time and expense make it unfeasible to follow a single cohort to estimate
      all the transition parameters. One difficulty of developing a model of chronic
      disease progression from such data is that the available studies often do not
      include the transitions of interest. For example, in our model of diabetic
      nephropathy, many clinical studies did not differentiate between patients without
      nephropathy and those who had microalbuminuria (a pre-clinical stage of
      nephropathy). Another difficulty was a lack of data to directly estimate
      parameters of interest. We consider models which can accommodate such
      difficulties. In this paper we consider the problem of estimating parameters of a
      discrete-time Markov process when longitudinal data describing the entire process
      are not available. First, we present a likelihood approach to estimate parameters
      of a discrete-time Markov model. Next, we use simulation to investigate the
      finite-sample behaviour of our approach. Finally, we present two examples: a
      model of diabetic nephropathy and a model of cardiovascular disease in diabetes.

PMID- 16416415
TI  - Painless legs moving toes in a patient with Wilson's disease.
AB  - We describe and present a video of a 20-year-old woman with Wilson's disease (WD)
      who developed the painless variant of painful legs and moving toes (PLMT)
      syndrome. The symptoms appeared during a subsequent minor exacerbation of her
      extrapyramidal symptomatology, only to gradually disappear 3 to 4 months later.
      We suggest that, in our case, a structural central nervous system lesion caused
      by WD may have been associated with the development of PLMT.

PMID- 16416416
TI  - Non-linearity in the cost-effectiveness frontier.
AB  - Conventional cost-effectiveness decision rules rely on the assumptions that all
      health care programmes are divisible and exhibit constant returns to scale for a
      homogeneous population; hence, the path between adjacent programmes on a cost
      effectiveness frontier must be linear. In this paper we build a framework to
      analyse non-linear 'expansion' paths. We model the impact of two key sources of
      non-linearity: economies of scale or scope in the production of health care; and
      prioritisation of patients who are most likely to benefit from more expensive and
      more effective treatments. We conclude that the expansion path might be linear,
      convex or concave, depending on the situation. The path might also exhibit
      vertical discontinuity due to fixed costs or horizontal discontinuity due to
      indivisibility. The efficiency of resource allocation might be improved by
      empirical estimation of expansion paths. We discuss the advantages and
      disadvantages of this approach compared with a standard stratified analysis.

PMID- 16416417
TI  - Interembryonic regions of the uterus of the viviparous lizard Mabuya brachypoda
      (Squamata: Scincidae).
AB  - Analysis of the structure and physiology of the uterine incubation chambers of
      viviparous squamates has provided insight concerning adaptations for gestation.
      However, the literature addressing the biology of the interembryonic regions of
      the uterus is very limited, presumably because it has been assumed that this area
      has little role in the development and support of embryos in viviparous
      squamates. This study was undertaken to examine the histology of the
      interembryonic regions of Mabuya brachypoda, a viviparous lizard with
      microlecithal ova and consequently substantial matrotrophic activity. The
      incubation chambers are oval, distended zones of the uterus, adjacent to the
      interembryonic regions. The wall of the interembryonic regions includes: mucosa,
      formed by a cuboidal or columnar epithelium with ciliated and nonciliated cells,
      and a lamina propria of vascularized connective tissue containing abundant acinar
      glands; myometrial smooth muscle consisting of inner circular and outer
      longitudinal layers; and serosa. The segment of the interembryonic region
      adjacent to the incubation chamber forms a transitional segment that displays
      folds of the mucosa that protrude into the uterine lumen. The limit of the
      incubation chamber is well defined by the long mucosal folds of the transitional
      segment. Long and thin extensions of extraembryonic membranes are present in the
      lumen of the transitional segment, outside of the incubation chamber region. The
      presence of abundant uterine glands and extraembryonic membranes in the
      interembryonic regions during gestation suggests uterine secretory activity and
      histotrophic transfer of nutrients to embryos in these regions.

PMID- 16416418
TI  - Antennal and cephalic organelles in the social wasp Paravespula germanica
      (Hymenoptera, Vespinae): form and possible function.
AB  - This paper deals with hairs and organelles present on the head and antennae of
      the German wasp, Paravespula germanica, and their possible role in sensing the
      physical and chemical ambience, as well as in intercommunicating both while in
      flight outside or in the nest. Via scanning electron microscope photography, we
      detected on the frons plate of the wasp's head, hairs that were about 300 microm
      long and comprised the longest hairs on the body of the wasps. Additionally, the
      two antennae bore along their entire length photoreceptors, placoids,
      campaniforms, trichoids, and agmons. These organelles are located at high but
      variable density along the antennal segments. The paper provides the dimensions
      of each of the mentioned organelles, and discusses the possible functions of the
      organelles as well as of the hairs on the frons. Photographs taken via atomic
      force microscope reveal that the epicuticle of the antenna is of two typical
      shapes; one, bearing both longitudinal stripes as well as transverse bands that
      are about 1 mum in width, and a second granulated form. Conceivably, the wasp
      uses the various organelles mentioned to communicate with its mates that are some
      distance away, somewhat like the use of radar by humans.

PMID- 16416419
TI  - Fetal and neonatal histiocytoses.
AB  - PURPOSE: The histiocytoses are a group of disorders of the monophagocytic system
      having a variety of clinical and pathological findings. They occur less often
      during the perinatal period than later in life. Their biologic behavior, response
      to therapy, and histologic types are not the same. METHODS: The study consisted
      of 221 fetuses and neonates collected from the literature and from personal
      files. RESULTS: Langerhans' cell histiocytosis (LCH), the hemophagocytic
      lymphohistiocytoses (HLH), and juvenile xanthogranuloma (JXG), in order of rank,
      were the main histiocytoses occurring in the perinatal period. HLH accounted for
      the highest mortality (74%) followed by disseminated LCH (52%) and JXG (11%). All
      neonates with LCH and JXG limited to the skin and/or subcutaneous tissue survived
      with or without treatment. CONCLUSIONS: This study suggests that there is an
      increased incidence of spontaneous regression of certain histiocytic lesions in
      neonates as compared to older individuals. Cutaneous forms JXG and LCH had the
      highest incidence of regression followed by infection associated HLH.

PMID- 16416420
TI  - Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits
      Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism.
AB  - The beta-cell ATP-sensitive potassium channel is a key component of stimulus
      secretion coupling in the pancreatic beta-cell. The channel couples metabolism to
      membrane electrical events, bringing about insulin secretion. Given the critical
      role of this channel in glucose homeostasis, it is not surprising that mutations
      in the genes encoding for the two essential subunits of the channel can result in
      both hypo- and hyperglycemia. The channel consists of four subunits of the
      inwardly rectifying potassium channel Kir6.2 and four subunits of the
      sulfonylurea receptor 1. It has been known for some time that loss of function
      mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1,
      can cause oversecretion of insulin and result in hyperinsulinemia (HI) of
      infancy; however, heterozygous activating mutations in KCNJ11 that result in the
      opposite phenotype of diabetes have recently been described. This review focuses
      on reported mutations in both genes, the spectrum of phenotypes, and the
      implications for treatment when patients are diagnosed with mutations in these
      genes.

PMID- 16416421
TI  - Application of a geographic information system to explore associations between
      air pollution and micronucleus frequencies in African American children and
      adults.
AB  - Exposure to air pollution has been associated with adverse respiratory and
      cardiovascular health outcomes in both children and adults. In this study, we
      used geographic information systems (GISs) to explore possible associations
      between chromosomal damage in 65 African American children and their mothers from
      Oakland, California, and both proximity to traffic and regional ozone levels.
      Study participants were interviewed at the Healthy Child Clinic of Children's
      Hospital, Oakland, and their blood and buccal cells were collected for assessment
      of chromosomal damage by the micronucleus (MN) assay. Regional ozone levels,
      which decreased from April to November with a secondary peak in late summer, were
      highly correlated with season by month (r=-0.84, P=0.02) and strongly associated
      with MN frequency (frequency ratio (FR): 3.37, 95% confidence interval (CI): 1.30
      8.72) in both cell types of children and adults. Additionally, MN frequencies
      were modestly associated with individual measures of traffic density in children
      (FR=2.45, 95% CI=0.86-7.10), but not in adults; this suggests a greater
      vulnerability to traffic-related air pollution in children. Smoking in the
      household also increased MN frequency in the lymphocytes of children (FR: 1.13,
      95%CI: 1.01-1.24) and adults (FR: 1.06, 95%CI: 0.99-1.13), whereas vitamin use in
      adults decreased MN frequency in both lymphocytes and buccal cells (FR: 0.17,
      95%CI: 0.02-1.31; FR: 0.18, 95%CI: 0.03-1.18, respectively). Our data indicate
      that GIS-generated measures of traffic density for individual households augment
      regional ozone monitoring data used to assess effects of air pollution. This
      approach helped to demonstrate elevated cytogenetic damage in exposed minority
      children.

PMID- 16416422
TI  - Conditional gene recombination by adenovirus-driven Cre in the mouse uterus.
AB  - Cre-mediated conditional gene targeting has been shown to be successful in many
      cell and tissue types. However, gene recombination in the uterus with
      heterogeneous cell types by Cre activation is not yet well established. Using
      recombinant adenoviruses expressing a functional Cre (ADV-Cre) and ROSA26
      reporter mice, we show here that ADV-Cre infused intraluminally in a small volume
      (10 microl) conditionally excises the loxP site, resulting in lacZ expression in
      uterine luminal epithelial cells without significantly affecting pregnancy. In
      contrast, a similar intraluminal infusion of ADV-Cre in a larger volume (50
      microl) damages the normal architecture and integrity of the luminal epithelium,
      inducing gene recombination in the underneath stromal cells, with disruption of
      pregnancy. Further, decidualizing stromal cells at the implantation sites can be
      targeted by ADV-Cre after intravenous administration on days 5-6. This route of
      administration also elicits Cre activity in other tissues, including the liver,
      spleen, ovary, and, more remarkably, in the adrenal cortex. These findings
      demonstrate the feasibility of achieving conditional expression or deletion of
      specific genes in uterine cells at desired times and physiological states.

PMID- 16416423
TI  - Monoclonal antibodies to distinct regions of human myelin proteolipid protein
      simultaneously recognize central nervous system myelin and neurons of many
      vertebrate species.
AB  - Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a
      member of the proteolipid gene family (pgf). It is an evolutionarily conserved
      polytopic integral membrane protein and a potential autoantigen in multiple
      sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ,
      monoclonal antibodies (mAbs) specific for different regions of human PLP (50-69,
      100-123, 139-151, 178-191, 200-219, 264-276) were generated and used to
      immunostain CNS tissues of representative vertebrates. mAbs to each region
      recognized whole human PLP on Western blots; the anti-100-123 mAb did not
      recognize DM-20, the PLP isoform that lacks residues 116-150. All of the mAbs
      stained fixed, permeabilized oligodendrocytes and mammalian and avian CNS tissue
      myelin. Most of the mAbs also stained amphibian, teleost, and elasmobranch CNS
      myelin despite greater diversity of their pgf myelin protein sequences. Myelin
      staining was observed when there was at least 40% identity of the mAb epitope and
      known pgf myelin proteins of the same or related species. The pgf myelin proteins
      of teleosts and elasmobranchs lack 116-150; the anti-100-123 mAb did not stain
      their myelin. In addition to myelin, the anti-178-191 mAb stained many neurons in
      all species; other mAbs stained distinct neuron subpopulations in different
      species. Neuronal staining was observed when there was at least approximately 30%
      identity of the PLP mAb epitope and known pgf neuronal proteins of the same or
      related species. Thus, anti-human PLP epitope mAbs simultaneously recognize CNS
      myelin and neurons even without extensive sequence identity. Widespread anti-PLP
      mAb recognition of neurons suggests a novel potential pathophysiologic mechanism
      in MS patients, i.e., that anti-PLP antibodies associated with demyelination
      might simultaneously recognize pgf epitopes in neurons, thereby affecting their
      functions.

PMID- 16416424
TI  - Inhibitors of the alpha-ketoglutarate dehydrogenase complex alter [1-13C]glucose
      and [U-13C]glutamate metabolism in cerebellar granule neurons.
AB  - Diminished activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), an
      important component of the tricarboxylic acid (TCA) cycle, occurs in several
      neurological diseases. The effect of specific KGDHC inhibitors [phosphonoethyl
      ester of succinyl phosphonate (PESP) and the carboxy ethyl ester of succinyl
      phosphonate (CESP)] on [1-13C]glucose and [U-13C]glutamate metabolism in intact
      cerebellar granule neurons was investigated. Both inhibitors decreased formation
      of [4-13C]glutamate from [1-13C]glucose, a reduction in label in glutamate
      derived from [1-13C]glucose/[U-13C]glutamate through a second turn of the TCA
      cycle and a decline in the amounts of gamma-aminobutyric acid (GABA), aspartate,
      and alanine. PESP decreased formation of [U-13C]aspartate and total glutathione,
      whereas CESP decreased concentrations of valine and leucine. The findings are
      consistent with decreased KGDHC activity; increased alpha-ketoglutarate
      formation; increased transamination of alpha-ketoglutarate with valine, leucine,
      and GABA; and new equilibrium position of the aspartate aminotransferase
      reaction. Overall, the findings also suggest that some carbon derived from alpha
      ketoglutarate may bypass the block in the TCA cycle at KGDHC by means of the GABA
      shunt and/or conversion of valine to succinate. The results suggest the potential
      of succinyl phosphonate esters for modeling the biochemical and
      pathophysiological consequences of reduced KGDHC activity in brain diseases.

PMID- 16416425
TI  - Optimization of chronic stress paradigms using anxiety- and depression-like
      behavioral parameters.
AB  - Chronic stress is a risk factor for psychiatric illnesses, such as anxiety and
      depression disorders. To understand the underlying mechanism regarding how
      chronic stress triggers such psychiatric dysfunctions, restraint-based chronic
      stress models have been attempted in the past. However, total durations of
      repeated restraint stress and the evaluation time points used after the last
      restraint application vary from experiment to experiment. One reason for these
      methodological heterogeneities is related to considerable ambiguity concerning
      the definition of chronic stress, particularly in animal models. In the present
      study, we used behavioral traits, anxiety and depression, as stress-assessment
      parameters that meet operationally useful requirements for the definition of the
      chronic stress state. We demonstrate that restraint treatment for 2 or 8 hr daily
      for 14 days is enough to produce anxiety- and depression-like behaviors, whereas
      a 2 hr-10 days restraint was marginally effective. cDNA microarray analysis
      identified 34 genes in the hippocampus and 72 genes in the amygdala with
      expression levels that were up- or down-regulated by >2.0-fold. Among the wide
      range of genes identified in this analysis, genes required for energy metabolism,
      signal transduction, transcription, synaptic plasticity, and remodeling of the
      brain architecture were notable. Our results suggest that the psychiatric
      criteria of anxiety and depression can be used as chronic stress-assessment
      parameters and that a restraint stress paradigm consisting of restraint treatment
      for 2 or 8 hr daily for 14 days could be used as a prototype paradigm for chronic
      stress studies.

PMID- 16416426
TI  - In vivo detection of single cells by MRI.
AB  - The use of high-relaxivity, intracellular contrast agents has enabled MRI
      monitoring of cell migration through and homing to various tissues, such as
      brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect
      single cells in vivo, homing to tissue, following cell labeling and
      transplantation. Primary mouse hepatocytes were double-labeled with green
      fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal
      labeling dye, and injected into the spleens of recipient mice. This is a common
      hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from
      the spleen to the liver as single cells. One month later the animals underwent in
      vivo MRI and punctuated, dark contrast regions were detected scattered through
      the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in
      combination with histological evaluation confirmed the presence of dispersed
      single hepatocytes grafted into the livers. Appropriate controls were used to
      determine whether the observed contrast could have been due to dead cells or free
      particles, and the results confirmed that the contrast was due to disperse,
      single cells. Detecting single cells in vivo opens the door to a number of
      experiments, such as monitoring rare cellular events, assessing the kinetics of
      stem cell homing, and achieving early detection of metastases.

PMID- 16416427
TI  - No association of endometriosis with galactose-1-phosphate uridyl transferase
      mutations in a Chinese population.
AB  - The linkage between endometriosis and galactose-1-phosphate uridyl transferase
      gene (GALT) mutations is controversial. In this study, the prevalence of the most
      common GALT mutations, Q188R and N314D, was assessed in women with endometriosis
      in a Chinese population. Three hundred twenty five unrelated women with
      endometriosis were enrolled. Samples of umbilical cord blood obtained from 310
      female newborn infants were used as population controls. Genomic DNA isolated
      from endometriosis patients and controls were subjected to multiple polymerase
      chain reactions to determine the Q188R and N314D mutations. There was no
      significant difference in the frequencies of the Q188R and N314D mutations
      between endometriosis patients and controls. The endometriosis patients were
      further divided into subgroups of stage III and IV disease, but still no
      statistically significant differences were observed in the frequency of the Q188R
      and N314D mutations between any of these groups and the controls. These findings
      suggest that Q188R and N314D mutations are not likely to be associated with an
      increased risk of endometriosis among Chinese Women.

PMID- 16416428
TI  - Quercetin reduces chromosome aberrations induced by atrazine in the Allium cepa
      test.
AB  - Quercetin is a widely distributed plant flavonoid possessing a variety of
      chemical and biological activities, including chelation, free-radical scavenging,
      and antioxidant activity. Atrazine is a selective triazine herbicide that has
      been the subject of an international revision program for human and ecological
      health risks because of its persistence in the environment. In a previous study,
      we demonstrated that atrazine was clastogenic in the Allium cepa test. In this
      present study, we investigated whether quercetin affords protection from the
      chromosome breaks induced by atrazine. In a preliminary assay, 0.1-20 microg/ml
      quercetin produced no toxicity or clastogenic activity in the Allium cepa test.
      Subsequently, we evaluated the effects of 0.5 and 5 microg/ml quercetin on the
      clastogenicity of 2.5, 5.0, and 7.5 microg/l atrazine. Quercetin (0.5 microg/ml)
      significantly reduced the frequency of total aberrations induced by 7.5 microg/l
      atrazine, while both concentrations of quercetin significantly decreased the
      frequency of fragments induced by 7.5 microg/l atrazine. The results of this
      study indicate that plant flavonoids such as quercetin may protect against the
      genotoxic effects of atrazine. Efforts to understand the extent to which plant
      flavonoids influence the biological activities of genotoxicants and the
      mechanisms involved in the interactions could help to better discern the
      advantages and disadvantages of their use and to clarify their possible
      protective role against pollutants.

PMID- 16416429
TI  - Searching PubMed for molecular epidemiology studies: the case of chromosome
      aberrations.
AB  - The available tools for searching literature in the field of Molecular
      Epidemiology are largely unsatisfactory. To identify major problems in retrieving
      information on this discipline, we comment here on the results of a literature
      search on cytogenetic biomarkers in children exposed to environmental pollutants.
      The search, done on the PubMed/MedLine database, was based on a strategy
      combining descriptors listed in the PubMed Medical Subject Headings (MeSH)
      Thesaurus and other available tools (free text or phrase search tools). 178
      articles were retrieved by searching the period from January 1, 1980 to November
      30, 2004. Only 2 of the 178 articles were indexed by the MeSH term "Epidemiology,
      molecular" (introduced in 1994) and 30 of 178 by the MeSH term "Biological
      markers" (introduced in 1989). The case of chromosome aberration (CA) was
      emblematic of the problem: 44 of 78 articles (56.4%) were not pertinent to the
      search. The reasons for this poor performance are reported and discussed. Authors
      and indexers may be able to improve the efficiency of article retrieval in the
      field of molecular epidemiology by using relevant terms in the title and
      abstract. This may suggest appropriate MeSH terms to the indexers for the
      indexing process. As regards the difficulty in identifying population studies
      using CA, the introduction of a specific MeSH term for chromosome aberrations
      when used as a biomarker would improve the search process.

PMID- 16416431
TI  - Balanced alternating steady-state elastography.
AB  - A conventional balanced steady-state free precession (b-SSFP) sequence scheme was
      modified such that the dynamic equilibrium becomes very sensitive to small cyclic
      displacements, generating two distinct and alternating steady states. This novel
      technique is proposed for the visualization of propagating transverse acoustic
      shear waves, as used in MR elastography (MRE) to determine the mechanical
      properties of materials or in vivo soft tissue. Experiments with tissue-like
      agarose gel phantoms and simulations demonstrate that the novel sequence offers
      an increase in phase sensitivity by about one order in magnitude compared to
      standard motion-encoding methods. In addition, the new method benefits from the
      very short acquisition times achieved by b-SSFP protocols.

PMID- 16416430
TI  - Model-free arterial spin labeling quantification approach for perfusion MRI.
AB  - In this work a model-free arterial spin labeling (ASL) quantification approach
      for measuring cerebral blood flow (CBF) and arterial blood volume (aBV) is
      proposed. The method is based on the acquisition of a train of multiple images
      following the labeling scheme. Perfusion is obtained using deconvolution in a
      manner similar to that of dynamic susceptibility contrast (DSC) MRI. Local
      arterial input functions (AIFs) can be estimated by subtracting two perfusion
      weighted images acquired with and without crusher gradients, respectively.
      Furthermore, by knowing the duration of the bolus of tagged arterial blood, one
      can estimate the aBV on a voxel-by-voxel basis. The maximum of the residue
      function obtained from the deconvolution of the tissue curve by the AIF is a
      measure of CBF after scaling by the locally estimated aBV. This method provides
      averaged gray matter (GM) perfusion values of 38 +/- 2 ml/min/100 g and aBV of
      0.93% +/- 0.06%. The average CBF value is 10% smaller than that obtained on the
      same data set using the standard general kinetic model (42 +/- 2 ml/min/100 g).
      Monte Carlo simulations were performed to compare this new methodology with
      parametric fitting by the conventional model.

PMID- 16416432
TI  - Influence of SENSE on image properties in high-resolution single-shot echo-planar
      DTI.
AB  - Limited spatial resolution is a key obstacle to the study of brain white matter
      structure with diffusion tensor imaging (DTI). In its frequent implementation
      with single-excitation spin-echo echo-planar sequences, DTI's ability to resolve
      small structures is strongly restricted by T2 and T2* decay, B0 inhomogeneity,
      and limited signal-to-noise ratio (SNR). In this work the influence of
      sensitivity encoding (SENSE) on diffusion-weighted (DW) image properties is
      investigated. Computer simulations showed that the PSF becomes narrower with
      increasing SENSE reduction factors, R, enhancing the intrinsic resolution. After
      a brief theoretical discussion, we describe the estimation of SNR on a pixel-by
      pixel basis as a function of R. The mean image SNR behavior is manifold: SENSE is
      capable of increasing SNR efficiency by reducing the echo time (TE). Each SNR(R)
      curve reveals a maximum that depends on the amount of partial Fourier encoding
      used. The overall best SNR efficiency for an eight-element head coil array and a
      b-factor of 1000 s/mm2 is achieved at R = 2.1 and partial Fourier encoding of
      60%. In vivo tensor maps of volunteers and a patient, with an in-plane resolution
      of 0.78 x 0.78 mm2, are also presented to demonstrate the practical
      implementation of the parallel approach.

PMID- 16416433
TI  - 2D axial moving table acquisitions with dynamic slice adaptation.
AB  - A method for axial multi-slice imaging during continuous table motion has been
      developed and implemented on a clinical scanner. Multiple axial slice packages
      are acquired consecutively and combined to cover an extended longitudinal FOV. To
      account for the table motion during the acquisition, the RF pulse frequencies are
      continuously updated according to the actual table velocity and slice position.
      Different strategies for the spatial-temporal acquisition sequence with extended
      FOV are proposed. They cover different regimes of scan requirements regarding
      table velocity, used scan range, and slice resolution. The method is easy to
      implement and compatible with most kinds of sequences. The robustness of the
      proposed approach has been tested in phantom studies and healthy volunteers using
      T1-, T2-, and STIR-weighted multi-slice techniques that are based on gradient and
      turbo spin echo sequences and compared to a stationary approach usually used in
      clinical routine. The method provides artifact free gradient echo based images
      during continuous table motion, while for turbo spin echo sequences limitations
      in choosing table translations occur due to gradient non-linearity effects.

PMID- 16416434
TI  - Optimized clinical T2 relaxometry with a standard CPMG sequence.
AB  - PURPOSE: To optimize the accuracy and precision of T2 measurements using the
      standard Carr-Purcell-Meiboom-Gill (CPMG) sequence. T2 values obtained with this
      technique are normally sensitive to imperfect refocusing due to the formation of
      unwanted stimulated echoes. MATERIALS AND METHODS: Modifications are made to the
      refocusing slice selection width and the interleaving scheme. A widened
      refocusing slice improves the uniformity of the refocusing flip angle across the
      slice. A slow spin echo acquisition provided "gold standard" T2 values. Repeated
      T2 measurements in phantom and human studies are used to compare the accuracy and
      precision of the optimized and non-optimized CPMG implementations. RESULTS: The
      required slice thickness ratio between refocusing and excitation slice widths is
      found to be 3:1 for typical optimized radiofrequency pulses. T2 values obtained
      using this optimized implementation more closely correspond to "gold standard"
      values. Repeated T2 measurements indicate significantly improved correspondence
      between data and model. A reduction in the fitting error of approximately 70% is
      demonstrated for phantoms. CONCLUSION: We demonstrate that a relatively simple
      change to the CPMG relaxometry sequence parameters from the default setup yields
      significant improvements in the accuracy and precision of T2 measurements.

PMID- 16416435
TI  - A parallel approach to STAP implementation for fMRI data.
AB  - PURPOSE: To exploit the capabilities of parallel processing in applying the space
      time adaptive processing (STAP) algorithm, previously explored on a small scale
      for functional magnetic resonance imaging (fMRI) applications, to conventional
      size fMRI data sets. MATERIALS AND METHODS: STAP is a two-dimensional filter that
      is able to locate fMRI activations in both space and frequency. It is applied
      here for the construction of brain activation maps in fMRI using Visual Age C,
      incorporating Engineering and Scientific Subroutine Library (ESSL) functions,
      compiled in 64-bit, and executed on an IBM SP supercomputer. RESULTS: Computer
      simulations incorporating actual MRI noise indicate that STAP, incorporated using
      the method of steepest descent, is feasible on conventional size data sets and
      exhibits an improvement in detecting activations over the more traditional cross
      correlation method of fMRI analysis when the response is unknown. CONCLUSION:
      STAP is feasible on traditional size fMRI data sets and useful in elucidating
      spatial and temporal connectivity.

PMID- 16416436
TI  - Repeatability of functional MRI for conformal avoidance radiotherapy planning.
AB  - PURPOSE: To establish the repeatability of functional magnetic resonance imaging
      (fMRI) examinations in order to develop an appropriate margin for functional
      organs at risk (fOAR) in the radiotherapy planning process. MATERIALS AND
      METHODS: This work investigates the variability of motor cortex activation in the
      left and right hemispheres of 15 normal subjects. The uncertainty of the absolute
      position and volume of the activation was determined for each volunteer by
      repeating the fMRI examination three times in a single scan session. RESULTS: Our
      study proposes the use of 2.9 mm and 2.2 mm margins for the left and right motor
      cortices, respectively. CONCLUSION: From the sample of 15 volunteers we
      established an appropriate planning margin that is considered to represent the
      uncertainty in spatially measuring the fOAR for a single fMRI examination. The
      work will be of interest to anyone investigating the clinical robustness of fMRI.

PMID- 16416437
TI  - Feasibility of k-t BLAST technique for measuring "seven-dimensional" fluid flow.
AB  - PURPOSE: To investigate the feasibility of rapid MR measurement of "seven
      dimensional" (three velocity components, three dimensions, and time) fluid flow
      using the k-t Broad-use Linear Acquisition Speed-Up Technique (BLAST). MATERIALS
      AND METHODS: Complete k-space data were acquired for pulsatile fluid flow in a
      model of a stenosed carotid bifurcation. The data was subsampled to simulate
      "training" and "accelerated acquisition" data for reconstruction using k-t BLAST.
      RESULTS: Flow waveforms estimated from k-t BLAST reconstructions were in good
      agreement with those measured from the full data set for overall speedup factors
      up to approximately four times when slice-by-slice undersampling in k(y) was
      used. Accuracy was better than 25 mm/second or 7% (root-mean-square error) for
      individual time frames under these conditions. Flow patterns in the plane of
      symmetry, near the bifurcation, and in the stenosis were also in good agreement
      with those reconstructed from the full data set. Improved performance was
      obtained from undersampling in both k(y) and k(z), when acceleration factors up
      to 12 times gave acceptable results. CONCLUSION: The k-t BLAST technique can be
      applied to flow quantification, and may make feasible the acquisition of time
      resolved blood flow from extended arterial regions within acceptable examination
      times.

PMID- 16416439
TI  - Hepatocellular carcinoma missed on gadolinium enhanced MR imaging, discovered in
      liver explants: retrospective evaluation.
AB  - The main purpose of this study was to determine if hepatocellular carcinomas
      (HCCs) missed on prospective magnetic resonance (MR) study could be identified on
      retrospective MR analysis, and to determine the cause for misdiagnosis. Among 555
      patients who underwent liver transplantation between 1993 and 2004, 279 were
      imaged with MR imaging and four of these revealed HCCs in explanted livers that
      were not reported on prospective MR reading. The main cause of missed lesions
      were suboptimal image quality due to inability of patients to suspend
      respiration; other causes were HCC misinterpreted as high-grade dysplastic nodule
      and isoenhancement of HCC on early phase images.

PMID- 16416438
TI  - Subjects' expectations in neuroimaging research.
AB  - PURPOSE: To explore subjects' attitudes and expectations concerning the detection
      and management of incidental findings in neuroimaging research. MATERIALS AND
      METHODS: Healthy control subjects (N = 105) who previously participated in
      neuroimaging studies in medical and nonmedical settings were surveyed about their
      expectations and attitudes toward unexpected clinical findings on their research
      brain scans. We hypothesized that even though the participants consented to a
      scanning procedure for research purposes alone, they would still expect
      pathology, if present, to be detected and reported to them. RESULTS: Fifty-four
      percent of participants reported that they expected research scans to detect
      abnormalities if they existed. Nearly all subjects (>90%) reported that they
      would want findings communicated to them, and many (59%) preferred this to be
      done by a physician affiliated with the research team. The participants responded
      in similar ways whether they were scanned in medical or nonmedical settings.
      CONCLUSION: Clarity about procedures for handling incidental findings when
      obtaining written and verbal informed consent is essential to ensure that the
      subjects' expectations are consistent with the purpose and scope of the research.

PMID- 16416440
TI  - Magnetic resonance imaging of myocardial infarction using a manganese-based
      contrast agent (EVP 1001-1): preliminary results in a dog model.
AB  - PURPOSE: To investigate the MRI characteristics of an intracellular manganese
      based contrast agent, EVP 1001-1 (Eagle Vision Pharmaceutical Corp.), in a canine
      model of myocardial infarction. MATERIALS AND METHODS: Three dogs were imaged 14
      37 days following permanent ligation of the left anterior descending coronary
      artery (LAD). Measurements of the longitudinal relaxation rate R(1) were made
      prior to EVP 1001-1 administration (20 micromol/kg i.v.) and for one hour
      thereafter. Triphenyl tetrazolium chloride (TTC) staining was used to document
      infarction. RESULTS: In normal myocardium, EVP 1001-1 produced a substantial
      increase in the longitudinal relaxation rate, which remained fairly constant over
      the postcontrast imaging period (DeltaR1= 1.47 +/- 0.58 sec(-1) (mean +/- SD) at
      35 minutes, P < 0.05). In the infarct, the response to EVP 1001-1 was small or
      negligible (DeltaR1= 0.27 +/- 0.28 sec(-1)). This resulted in a significant
      postcontrast difference in relaxation rate between normal and infarcted tissue
      (R1(normal) - R1(infarct) = 1.08 +/- 0.26 sec(-1), P < 0.05). The infarct
      remained clearly delineated in all animals throughout the steady-state imaging
      period, and qualitatively matched TTC results. CONCLUSION: The persistent
      enhancement pattern revealed by MRI following EVP 1001-1 administration may be
      beneficial for identifying and characterizing myocardial infarction.

PMID- 16416442
TI  - Quantitative phase-contrast flow MRI measurements in the presence of a second
      vessel closely positioned to the examined vessel.
AB  - PURPOSE: To examine the influence of the truncated sampling of k-space data on
      the accuracy of phase-contrast (PC) flow quantifications in the presence of
      nearby vessels. MATERIALS AND METHODS: Computer simulations were performed along
      with some experimental validations on a flow phantom and a normal subject.
      RESULTS: The accuracy of the PC flow quantification decreased when a second
      vessel was positioned closely to the examined vessel. The effect strongly
      depended on the peak flow velocity in the second vessel relative to the velocity
      encoding (venc) level of the MRI acquisition, and on the position and area of the
      second vessel. CONCLUSION: Due to the truncated sampling of the k-space data,
      signal leaked from nearby vessels and distorted the PC flow quantification in the
      examined vessel. The presented results suggest specific experimental conditions
      to minimize this flow quantification error.

PMID- 16416441
TI  - Toward rapid high resolution in vivo intravascular MRI: evaluation of vessel wall
      conspicuity in a porcine model using multiple imaging protocols.
AB  - PURPOSE: To assess magnetic resonance (MR) pulse sequences for high resolution
      intravascular imaging. MATERIALS AND METHODS: Intravascular imaging of the
      abdominal aorta and iliac arteries was performed in vivo in a porcine model at
      1.5 T using catheter-mounted micro-receive coils. Ten protocols, including spin
      echo (SE)-echo planar imaging (SE-EPI), segmented EPI, half-Fourier single-shot
      turbo spin-echo (HASTE), fast imaging with steady-state free precession
      (TrueFISP), turbo spin-echo (TSE), and SE acquisition schemes were employed in 13
      trials. Images were analyzed by six expert raters with respect to wall
      conspicuity, wall-to-lumen/tissue contrast, visible layers of the arterial wall,
      anticipated clinical usefulness, and overall image quality. Mean differences
      between sequence-types were evaluated using analysis of variance (ANOVA) between
      groups with planned comparisons. RESULTS: The vessel wall was delineated in
      almost all protocols. Motion artifacts from physiological and device motion were
      reduced in fast techniques. The best contrast between the wall and surrounding
      tissue was provided by a HASTE protocol. Anatomic layers of the vessel wall were
      best depicted on dark blood T2-weighted TSE. Overall, TrueFISP was ranked highest
      on the remaining measures. CONCLUSION: Dedicated catheter-coils combined with
      fast sequences have potential for in vivo characterization of vessel walls.
      TrueFISP offered the best overall image quality and acquisition speed, but
      suffered from the inability to delineate the multiple layers of the wall, which
      seems associated with dark blood- and T2-weighted contrast. We believe future
      intra-arterial trials should proceed from this study in normal artery imaging and
      initially focus on fast T2-weighted dark blood techniques in trials with
      pathology.

PMID- 16416443
TI  - Substrate-free structure of a monomeric NADP isocitrate dehydrogenase: an open
      conformation phylogenetic relationship of isocitrate dehydrogenase.
AB  - Both monomeric and dimeric NADP+-dependent isocitrate dehydrogenase (IDH) belong
      to the metal-dependent beta-decarboxylating dehydrogenase family and catalyze the
      oxidative decarboxylation from 2R,3S-isocitrate to yield 2-oxoglutarate, CO2, and
      NADPH. It is important to solve the structures of IDHs from various species to
      correlate with its function and evolutionary significance. So far, only two
      crystal structures of substrate/cofactor-bound (isocitrate/NADP) NADP+-dependent
      monomeric IDH from Azotobacter vinelandii (AvIDH) have been solved. Herein, we
      report for the first time the substrate/cofactor-free structure of a monomeric
      NADP+-dependent IDH from Corynebacterium glutamicum (CgIDH) in the presence of
      Mg2+. The 1.75 A structure of CgIDH-Mg2+ showed a distinct open conformation in
      contrast to the closed conformation of AvIDH-isocitrate/NADP+ complexes.
      Fluorescence studies on CgIDH in the presence of isocitrate/or NADP+ suggest the
      presence of low energy barrier conformers. In CgIDH, the amino acid residues
      corresponding to the Escherichia coli IDH phosphorylation-loop are alpha-helical
      compared with the more flexible random-coil region in the E. coli protein where
      IDH activation is controlled by phosphorylation. This more structured region
      supports the idea that activation of CgIDH is not controlled by phosphorylation.
      Monomeric NADP+-specific IDHs have been identified from about 50 different
      bacterial species, such as proteobacteria, actinobacteria, and planctomycetes,
      whereas, dimeric NADP+-dependent IDHs are diversified in both prokaryotes and
      eukaryotes. We have constructed a phylogenetic tree based on amino acid sequences
      of all bacterial monomeric NADP+-dependent IDHs and also another one with
      specifically chosen species which either contains both monomeric and dimeric
      NADP+-dependent IDHs or have monomeric NADP+-dependent, as well as NAD+-dependent
      IDHs. This is done to examine evolutionary relationships.

PMID- 16416444
TI  - Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain:
      a comparison of the agonist radioligand [11C]MNPA and antagonist [11C]raclopride.
AB  - PET measurements of stimulant-induced dopamine (DA) release are typically
      performed with antagonist radioligands that bind to both the high- and low
      affinity state of the receptor. In contrast, an agonist radioligand binds
      preferentially to the high-affinity state and is expected to have greater
      sensitivity to DA, which is the endogenous agonist. [(11)C]MNPA, (R)-2-CH(3)O-N-n
      propylnorapomorphine (MNPA), is a D(2) agonist radioligand with subnanomolar
      affinity to the D(2) receptor. The aim of the present study is to assess and
      compare the sensitivity of the agonist radioligand [(11)C]MNPA and antagonist
      radioligand [(11)C]raclopride to synaptic DA levels. Four cynomolgus monkeys were
      examined with [(11)C]MNPA and [(11)C]raclopride (16 PET measurements with each
      tracer) at baseline and after pretreatment with various doses of amphetamine. The
      effect of amphetamine was calculated by the change in binding potential (BP)
      analyzed with the multilinear reference tissue model (MRTM2). Amphetamine caused
      a reduction in [(11)C]MNPA BP of 4% at 0.1, 23% at 0.2, 25% at 0.5, and 46% at
      1.0 mg/kg. [(11)C]Raclopride BP was reduced to a lesser extent by 2% at 0.1, 16%
      at 0.2, 15% at 0.5, and 23% at 1.0 mg/kg. The data were used to estimate the in
      vivo percentage of high-affinity state receptors to be approximately 60%. These
      results demonstrate that [(11)C]MNPA is more sensitive than [(11)C]raclopride to
      displacement by endogenous DA, and that it may provide additional information
      about the functional state of the D(2) receptor in illnesses such as
      schizophrenia and Parkinson's disease.

PMID- 16416445
TI  - Alterations in alcohol consumption, withdrawal seizures, and monoamine
      transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan.
AB  - We have previously shown that coadministration of the dopamine (DA) agonist
      phentermine plus the serotonergic agonist fenfluramine suppresses alcohol intake
      and withdrawal seizures in rats. In the present study, phentermine and the
      serotonin (5-HT) precursor, 5-hydroxy-L-tryptophan (5-HTP), were administered
      alone, or in combination, to rats fed on a 6% alcohol-containing diet or an
      isocaloric control diet. Following a 9-h withdrawal period from the alcohol
      containing diet, phentermine enhanced the effects of 5-HTP on both reduction of
      alcohol withdrawal seizures as well as changes in striatal serotonin. Food intake
      was monitored for 24 h after drug treatment, and neurochemical measures were
      examined at various time points. Phentermine alone reduced food intake in all
      diet conditions, but this anorectic effect was followed by hyperphagia in control
      rats. Phentermine plus 5-HTP reduced the consumption of the alcohol-containing
      diet, while its effects on consumption of control diets were mixed. In vivo
      microdialysis in rat nucleus accumbens revealed that phentermine increased
      extracellular DA, whereas 5-HTP caused marked elevations in extracellular 5-HT.
      Coadministration of phentermine and 5-HTP evoked simultaneous elevations in
      extracellular DA and 5-HT that mirrored the effects of each drug alone.
      Collectively, these findings show that coadministered phentermine plus 5-HTP is
      effective in reducing alcohol intake and suppressing alcohol withdrawal seizures.
      These therapeutic actions may be related to elevations in synaptic DA and 5-HT in
      critical brain regions.

PMID- 16416447
TI  - Role of integrin beta1-like protein in proliferation and differentiation of
      cultured stem cells from midgut of Heliothis virescens.
AB  - Cultured midgut cells from Heliothis virescens larvae were incubated with anti
      human integrin beta1 made in rabbit and then passed over a column of magnetic
      beads bound to anti-rabbit IgG (MACS, Miltenyi Bergisch Gladbach, Germany). Cells
      bound to integrin beta1 antibody also bound to the anti-rabbit IgG on the
      magnetic beads (MACS) and were retained in the column while it remained in the
      magnetic field. Non-bound cells were eluted at this time. They did not stain with
      anti-integrin antibody just after elution. Removing the column from the magnetic
      field allowed cells bound to the beads-integrin beta1 antibody to be eluted. All
      of these cells stained with human anti-integrin beta1 upon elution. Each cell
      fraction was cultured in medium for 3 days. During this time, the populations of
      cells tended to return to heterogeneous staining patterns characteristic of
      control populations. However, cells that did not stain immediately with anti
      integrin beta1 antibody exhibited double the rate of multiplication and 8 times
      more differentiation than the integrin-antibody positive cells that eluted later,
      as well as the non-treated control cells. In a second experiment, midgut cells
      were incubated for 4 days with various titers of human anti-integrin beta1 to
      block surface integrin beta1-like reactive sites. Stem cells blocked with anti
      integrin beta1 antibody during incubation exhibited double the rate of
      differentiation than non-treated control cells and those showing anti-integrin
      beta1-positive stain upon elution.

PMID- 16416446
TI  - Effects of COX-1 and COX-2 inhibitors on the firing of rat midbrain dopaminergic
      neurons--possible involvement of endogenous kynurenic acid.
AB  - Kynurenic acid (KYNA) is an endogenous glutamate-receptor antagonist with a
      preferential action at the glycine-site of the NMDA-receptor. In the present in
      vivo study, the importance of brain KYNA to modulate the activity of dopamine
      (DA) neurons in the ventral tegmental area (VTA) was analyzed by utilizing the
      decrease in brain KYNA formation induced by the cyclooxygenase (COX)-2 inhibitor
      parecoxib. A reduction in brain KYNA concentration (39-44%) by parecoxib (25
      mg/kg, i.v., 1 h or, i.p., 3.5 h) was associated with a decreased firing rate and
      burst firing activity. In concordance, an increase in brain KYNA concentration
      (150-300%), induced by the COX-1 inhibitor indomethacin (50 mg/kg, i.v., 1 h or,
      i.p., 3.5 h), produced opposite effects, that is, increased firing rate and burst
      firing activity. The decrease and increase in neuronal firing of VTA DA neurons
      by the COX-inhibitors was reversed by L-701,324 (antagonist at the NMDA-glycine
      site; 0.06-2 mg/kg, i.v.) and by D-cycloserine (partial agonist at the NMDA
      glycine site; 2-32 mg/kg, i.v.), respectively. In addition, the parecoxib-induced
      decrease in firing rate and burst firing activity was effectively blocked by
      pretreatment with kynurenine (5 mg/kg, i.p., 30 min), the immediate precursor of
      KYNA. Present results suggest that the action of COX-inhibitors on the firing of
      VTA DA neurons are linked to their effects on KYNA formation and that endogenous
      KYNA is tonically modulating the neuronal activity of VTA DA neurons. Such a
      modulatory action of KYNA should be of importance for the functioning of
      mesocorticolimbic DA pathway.

PMID- 16416448
TI  - Structure and enzyme properties of Zabrotes subfasciatus alpha-amylase.
AB  - Digestive alpha-amylases play an essential role in insect carbohydrate
      metabolism. These enzymes belong to an endo-type group. They catalyse starch
      hydrolysis, and are involved in energy production. Larvae of Zabrotes
      subfasciatus, the Mexican bean weevil, are able to infest stored common beans
      Phaseolus vulgaris, causing severe crop losses in Latin America and Africa. Their
      alpha-amylase (ZSA) is a well-studied but not completely understood enzyme,
      having specific characteristics when compared to other insect alpha-amylases.
      This report provides more knowledge about its chemical nature, including a
      description of its optimum pH (6.0 to 7.0) and temperature (20-30 degrees C).
      Furthermore, ion effects on ZSA activity were also determined, showing that three
      divalent ions (Mn2+, Ca2+, and Ba2+) were able to enhance starch hydrolysis. Fe2+
      appeared to decrease alpha-amylase activity by half. ZSA kinetic parameters were
      also determined and compared to other insect alpha-amylases. A three-dimensional
      model is proposed in order to indicate probable residues involved in catalysis
      (Asp204, Glu240, and Asp305) as well other important residues related to starch
      binding (His118, Ala206, Lys207, and His304).

PMID- 16416449
TI  - Molecular cloning and expression of protein kinase C from Bombyx mori.
AB  - Two partial cDNA clones (Protein kinase C alpha and Protein kinase C iota), each
      of which encoded a different member of PKC-protein family, were isolated using RT
      PCR from mRNA of Bombyx mori. The full-length cDNAs were isolated using SMART
      RACE. The cDNAs were expressed in HepG2 cells and the recombinant proteins were
      partially purified using an affinity chromatography. Protein kinase C alpha (BPKC
      alpha) showed a calcium-dependent kinase activity of histones. Whereas protein
      kinase C iota (BPKC iota) showed a calcium-independent activity. Bisindolyl
      maleimide I, a PKC inhibitor, inhibited these kinase activities. Furthermore, in
      vitro BPKC alpha interacted and phosphorylated two proteins expressed in the
      brain of Bombyx mori: Rab protein, which plays important roles in the vesicle
      transport in the brain, and bMBD2/3, which is a methyl DNA-binding protein and
      regulates transcription. These results suggest that these PKCs phosphorylate
      various substrate proteins and function in the brain of Bombyx mori.

PMID- 16416451
TI  - Identification of methyl farnesoate from in vitro culture of the retrocerebral
      complex of adult females of the moth, Heliothis virescens (Lepidoptera:
      Noctuidae) and its conversion to juvenile hormone III.
AB  - Gas chromatographic-mass spectral analysis of extracts obtained from in vitro
      culture of isolated retrocerebral complexes obtained from adult females of the
      moth Heliothis virescens resulted in identification of methyl farnesoate as well
      as juvenile hormone III (JH III) but not JH III acid. Inhibition of JH
      biosynthesis by incubation of tissue in synthetic Manduca sexta allatostatin
      (Manse-AST, pGlu-Val-Arg-Phe-Arg-Gln-Cys-Tyr-Phe-Asn-Pro-Ile-Ser-Cys-Phe-COOH)
      reduced production of these chemicals to negligible levels. However, incubation
      of tissue in the presence of Manse-AST plus farnesol resulted in production of
      significant amounts of both methyl farnesoate and JH III. Tissue incubated in the
      presence of Manse-AST plus methyl farnesoate produced only JH III. The results
      indicated that methyl farnesoate is naturally produced by the corpora allata of
      adult females of Heliothis virescens. However, tissue incubated in the presence
      of Manse-AST plus JH III acid also produced JH III in amounts equivalent to that
      produced by tissue incubated with methyl farnesoate. Thus, both methyl farnesoate
      and JH III acid could serve as a precursor for biosynthesis of JH III.

PMID- 16416450
TI  - In vivo and in vitro activity of venom from the endoparasitic wasp Pimpla
      turionellae (L.) (Hymenoptera: Ichneumonidae).
AB  - The biological activity of venom from Pimpla turionellae L. (Hymenoptera:
      Ichneumonidae) was examined in vivo toward larvae and pupae of Galleriae
      mellonella L. (Lepidoptera: Pyralidae), and in vitro toward bacterial and fungal
      cultures, as well as cultured insect cells. Pupae of G. mellonella were far more
      susceptible to the venom than larvae. At low doses of venom [0.1 venom reservoir
      equivalents (VRE)], pupal abdominal mobility was inhibited within 30 min, and by
      24 h, all pupae injected with venom concentrations >0.5 VRE were completely
      paralyzed. These same doses of venom resulted in an inhibition of adult
      emergence. Host larvae were far less sensitive to wasp venom as evidenced by all
      venom injected larvae remaining responsive to mechanical stimulation by 1 h post
      injection, even at concentrations equivalent to 1 venom reservoir. Eventually (>2
      h at 25 degrees C), venom-injected larvae became immobile, then flaccid, and all
      died within 24 h post-injection. At lower concentrations of wasp venom, the onset
      of paralysis was delayed by comparison to that evoked by 1 VRE, and few host
      larvae were able to pupate. Development of host larvae to adult emergence was
      also reduced in a dose-dependent manner, with eclosion completely prevented at
      high concentrations (>0.5 VRE) of venom. Venom doses <0.5 VRE did not appear to
      induce paralysis or alter larval development. When venom was incubated with
      bacterial or fungal cultures, no antimicrobial activity was detected. However,
      wasp venom was found to be cytotoxic and cytolytic to cultured cells derived from
      the cabbage looper Trichoplusia ni Hubner (Lepidoptera: Noctuidae) and the yellow
      fever mosquito, Aedes aegypti (L.) (Diptera: Culcidae). Though both cell types
      displayed similar susceptibility in terms of LC50s, the lepidopteran cells
      responded much more rapidly with regard to the onset of morphological changes and
      the timing of cell death. A possible mode of action for the venom is discussed.

PMID- 16416452
TI  - Photochemical approach to probing different DNA structures.
AB  - The various conformations of DNA--the A, B, and Z forms, the protein-induced DNA
      kink, and the G-quartet form--are thought to play important biological roles in
      processes such as DNA replication, gene expression and regulation, and the repair
      of DNA damage. The investigation of local DNA conformational changes associated
      with biological events is therefore essential for understanding the function of
      DNA. In this Minireview, we discuss the use of photochemical dehalogenation of 5
      halouracil-containing DNA to probe the structure of DNA. Hydrogen abstraction by
      the resultant uracil-5-yl radicals is atom-specific and highly dependent on the
      structure of the DNA, suggesting that this photochemical approach could be
      applied as a probe of DNA conformations in living cells.

PMID- 16416453
TI  - Surface versus molecular siloxy ligands in well-defined olefin metathesis
      catalysts: [{(RO)3SiO}Mo(=NAr)(=CHtBu)(CH2tBu)].

PMID- 16416454
TI  - A novel electrochemical information storage system based on stripping voltammetry
      of metals.

PMID- 16416455
TI  - Conditionally replicative adenoviral vectors for malignant glioma.
AB  - High-grade gliomas constitute an important challenge to modern medicine, and
      although great effort has been made to prolong patient survival, the prognosis
      for this disease remains poor. Due to recent discoveries in the molecular basis
      of gliomas, gene therapy is becoming a promising alternative. In this review, we
      discuss the use of conditionally replicative adenoviral vectors (CRAd) and their
      applications in neuro-oncology. Such vectors, when rendered conditionally
      replicative via transductional and transcriptional modifications, offer great
      promise for patients with malignant brain tumours. We review data from
      preclinical and clinical studies utilising such vectors and discuss the
      limitations and future perspectives of CRAd oncolytic therapy for malignant
      glioma.

PMID- 16416456
TI  - Metal ions-dependent peroxidase and oxidoreductase activities of polyclonal IgGs
      from the sera of Wistar rats.
AB  - We present evidence showing that a small fraction of electrophoretically
      homogeneous IgGs from the sera of healthy Wistar rats is bound with several
      different Me2+ ions and oxidizes 3,3'-diaminobenzidine through a peroxidase
      activity in the presence of H2O2 and through an oxidoreductase activity in the
      absence of H2O2. During purification on Protein A-Sepharose and gel filtration,
      the polyclonal IgGs partially lose the Me2+ ions. Therefore, in the absence of
      external metal ions, the specific peroxidase activity of IgGs from the sera of
      different rats varied in the range 1.6-26% and increased up to 13-198% after
      addition of Fe2+ or Cu2+ ions as compared with horseradish peroxidase (HRP, taken
      for 100%). The oxidoreductase activity of HRP is 24-fold lower than its
      peroxidase activity, while oxidoreductase and peroxidase activities of IgGs are
      comparable. Oxidoreductase activities of different IgGs in the absence of
      external metal ions varied from 22 to 800%, and in the presence of Fe2+ or Cu2+
      ions, from 37 to 1100% in comparison with the HRP oxidoreductase activity (100%).
      Chromatography of the IgGs on Chelex-100 leads to the adsorption of a small IgG
      fraction bound with metal ions and to its separation to many different
      subfractions demonstrating various affinities to the chelating resin and
      increased levels of the specific oxidoreductase and peroxidase activities.
      Antioxidant enzymes such as superoxide dismutases, catalases, and glutathione
      peroxidases are known to represent critical defense mechanisms for preventing
      oxidative modifications of DNA, proteins, and lipids. Peroxidase and
      oxidoreductase activity of antibodies may play an important role in the
      protection of organisms from oxidative stress and toxic compounds.

PMID- 16416457
TI  - Well-being, physical functioning, and use of health services in the elderly with
      PTSD and subthreshold PTSD.
AB  - OBJECTIVE: To measure the impact of PTSD and subthreshold PTSD on daily life
      functioning, well-being and health care use in a community based-sample of the
      elderly population in the Netherlands. METHODS: Consequences of PTSD were
      investigated in an elderly community-based population (LASA study) by comparing
      three groups: subjects with PTSD, with subthreshold PTSD, and a reference group.
      Indicators of well-being (loneliness, self-perceived health and satisfaction with
      life), disability (days spent in bed and disability days) and use of health care
      (general practitioners, medical specialists, psychiatrists, mental health care,
      social workers and professional home care) were investigated. RESULTS: In
      comparison to the reference group, subjects with PTSD or subthreshold PTSD spent
      more days in bed due to illness and had more disability days, even when corrected
      for concurring other diseases or functional limitations. They were less satisfied
      with life in general, used health care for predominantly somatic care and
      evaluated the care they received to be inadequate. Psychotropic drugs, if
      prescribed, were predominantly benzodiazepines and seldom antidepressants.
      CONCLUSIONS: The findings strongly suggest that elderly with either PTSD or
      subthreshold PTSD suffer grave impairments in daily life, are less satisfied with
      life and do not receive optimum treatment. Especially elderly with PTSD
      frequently visit medical specialists but are rarely treated by psychiatrists or
      other mental health professionals, nor do they receive antidepressant treatment
      from their GP. Lack of adequate treatment may be the cause of dissatisfaction
      with the care they receive.

PMID- 16416459
TI  - Ethically justified clinical strategies for promoting geriatric assent.
AB  - OBJECTIVE: To develop ethically justified clinical strategies for promoting
      geriatric assent with a focus on the application of professional virtues. METHOD:
      The concept of geriatric assent was extended to all geriatric patients
      incapacitated by cognitive impairments, including dementias, and practical
      clinical steps for promoting geriatric assent were developed. RESULTS: A four
      step-process for promoting geriatric assent is proposed by balancing the
      principles of beneficence and respect for autonomy within the context of the
      psychiatrist's virtues. These four steps include identifying the patient's long
      standing values and preferences; assessing plans of care in terms of
      biopsychosocial safety and independence along with the patient's values and
      preferences; protecting remaining autonomy; and cultivating the professional
      virtues of steadiness, self-effacement, and self-sacrifice when making decisions
      that risk the patient's future health and safety. CONCLUSIONS: In promoting
      geriatric assent, psychiatrists are obligated to support and directively counsel
      the patient's surrogate to adopt care plans that promote the patient's values and
      preferences to the extent possible. These clinical strategies for promoting
      geriatric assent should serve to enhance the patient's remaining sense of
      integrity and dignity. These strategies should also protect remaining health
      status and therefore protect remaining autonomy.

PMID- 16416458
TI  - A comparison of the efficacy and safety of olanzapine and risperidone in the
      treatment of elderly patients with schizophrenia: an open study of six months
      duration.
AB  - BACKGROUND: Following an earlier study in which elderly patients with
      schizophrenia had their typical antipsychotic medication changed to olanzapine or
      risperidone, the 61 patients were followed for up to a further six months to see
      if either treatment was superior in terms of efficacy or side effects. AIMS: To
      determine whether either olanzapine or risperidone was superior in terms of
      efficacy or side effects when treating schizophrenia in late life. METHODS:
      Psychiatric symptoms, side effects and quality of life were rated every six weeks
      for 24 weeks of open label comparative treatment using standard measures. Group
      differences were examined using analysis of covariance and within-group changes
      over time were assessed using paired t-tests. RESULTS: There were 34 olanzapine
      and 32 risperidone patients who entered the study, but intention to treat data
      was only available for 61 of the 66 patients. There were no clinical or
      demographic differences between the groups. Parkinsonism, positive and negative
      symptoms of schizophrenia improved in both groups both from baseline switch to
      olanzapine or risperidone and during the six month follow-up after completion of
      crossover. No significant differences were seen between groups on most measures.
      However, patients treated with olanzapine showed a significantly greater
      improvement in quality of life from baseline compared to risperidone patients.
      CONCLUSIONS: Both drugs were well tolerated and their use was associated with
      fewer symptoms of schizophrenia and less adverse effects than were seen when the
      patients were taking a typical antipsychotic at baseline. Olanzapine appears to
      have particular benefit with regard to quality of life.

PMID- 16416460
TI  - Differences in heart rate variability between depressed and non-depressed
      elderly.
AB  - OBJECTIVE: To determine whether older primary care patients with a Major
      Depressive Disorder (MDD) have lower heart rate variability (HRV) compared to non
      depressed patients. HRV is a measure of cardiac autonomic functioning. METHOD: A
      cross-sectional comparison of 136 elderly persons with MDD and 136 non-depressed
      controls (matched for age and gender) recruited in family practices in the
      Netherlands. Depression was determined according to the DSM-IV criteria using the
      PRIME-MD. HRV was measured with an electrocardiogram (ECG) during a 5-minute
      supine rest. RESULTS: Multivariate analyses showed statistically significant
      decrease in HRV in MDD patients compared with controls. CONCLUSION: Older primary
      care patients with MDD have a reduced HRV. This may explain why depression is a
      risk factor for cardiovascular disease and mortality.

PMID- 16416461
TI  - Can risperidone and olanzapine in elderly patients with dementia and other mental
      disorders be discontinued?
AB  - BACKGROUND: In March 2004, the UK Committee of Safety of Medicines (CSM) informed
      clinicians that risperidone and olanzapine should not be used to treat
      behavioural and psychological symptoms of dementia (BPSD) because of increased
      risk of strokes with both drugs and increased risk of mortality with olanzapine.
      An audit to examine the implications of the implementation of the CSM guidance
      was undertaken. METHODS: All patients receiving these two drugs, in one
      psychogeriatric service, at the time of CSM guidance were identified and
      reviewed. Data on clinical and demographic features, patient and carer
      involvement in the review and clinical outcome of the efficacy of the overall
      treatment package at 6 month follow-up was ascertained from the case-notes.
      RESULTS: The main findings were: (i) all patients receiving risperidone or
      olanzapine were identified and reviewed at a median interval of 8 days after the
      CSM guidance; (ii) most patients and carers were involved in the initial review;
      (iii) risperidone and olanzapine were discontinued in 22 and 12 of the patients
      respectively, and in 19 of these patients another neuroleptic was substituted;
      (iv) there was no relationship between discontinuation of these two drugs and
      presence of cerebrovascular and cardiovascular risk factors; and, (v) there was
      no relationship between the clinical outcome of efficacy at six months and
      discontinuation of these two drugs. CONCLUSIONS: This study illustrates that it
      is possible to identify, review and follow-up patients on these two drugs and
      involve the patient and carer in the review, and clinical outcome of efficacy of
      the overall treatment package is not adversely affected by continuation or
      discontinuation of these two drugs.

PMID- 16416462
TI  - Biocompatibility of nanofilm-encapsulated silicone and silicone-hydrogel contact
      lenses.
AB  - A material placed in or in contact with a biological system, that causes the
      minimum perturbation that can be tolerated by the host biological system, can be
      considered to be biocompatible. The major effects caused by a contact lens can be
      considered to be 1) the blocking of the natural supply of oxygen to the
      epithelium cells of the cornea, 2) interference with the normal evaporation of
      water from the tear fluid layer, and 3) hindrance of the normal functions of
      blinking for replenishing oxygen-saturated tear fluid and removing dead
      epithelium cells, which result from apoptosis. The encapsulation of a highly
      oxygen-permeable contact lens by a nanofilm with an imperturbable surface state
      minimizes all these terms. The encapsulated contact lens can be worn safely in
      extended wear.

PMID- 16416463
TI  - Novel water-soluble quaternary piperazine derivatives of chitosan: synthesis and
      characterization.
AB  - Novel synthesis methods for the preparation of quaternary piperazine derivatives
      of chitosan were developed. Quaternary ammonium moiety can be selectively
      inserted into either one or both of the piperazine nitrogens, yielding
      structurally uniform chitosan derivative structures. Water-soluble end products
      were thoroughly characterized with FT-IR, 1H NMR, 13C NMR and 2D 1H-13C HSQC NMR.
      The molecular weights of the end products were determined by GPC with triple
      detection.

PMID- 16416464
TI  - Use of home care services effectively reduces feelings of burden among family
      caregivers of disabled elderly in Japan: preliminary results.
AB  - BACKGROUND: Relatively few observational studies have been conducted on the
      impact of home care services on burden or other aspects of the caregiver's
      experience. OBJECTIVES: To examine whether the use of care services reduces the
      feelings of burden among family caregivers in Japan. Specifically, the study was
      aimed at testing the following three hypotheses: (1) The severity of impairment
      and the dementia among the disabled elderly increases the feelings of burden
      among family caregivers and the support from family members decreases burden: (2)
      the amount of services used by older people and their caregivers is affected by
      the severity of dementia and ADL deficiencies among the disabled elderly and the
      amount of support from family members: and (3) controlling for severity, the use
      of care services under the LTC insurance program serves to reduce the feelings of
      burden among family caregivers. METHODS: A structural equation model using the
      data obtained from 82 pairs of community-dwelling disabled elderly and their
      principal family caregivers. The model included the following variables: age of
      the disabled elderly; the severity of ADL deficiency and behavioral disturbances;
      use of formal (public) care services; support from family members; and feelings
      of burden among family caregivers. RESULTS: The structural equation model
      revealed that, after controlling for the effects of severity on service use, home
      care services effectively reduce feelings of burden among family caregivers.
      CONCLUSIONS: The findings suggest that care services provided under the LTC
      insurance have been successfully reducing burden among family caregivers in the
      study area.

PMID- 16416465
TI  - Life-time history of suicide attempts and coronary artery disease in a community
      dwelling elderly population.
AB  - BACKGROUND: Numerous studies have observed a strong relationship between coronary
      artery disease (CAD) and psychiatric disorder; notably depression, anxiety and
      panic attacks. No study has, however, explored the question of whether persons
      suffering from CAD might also be at high risk of suicide attempts. OBJECTIVE: The
      aim of the present study is to examine the relationship between CAD within a
      general population cohort and life-time history of psychiatric disorder and
      suicidal behaviour. METHOD: A representative sample of 1,843 non
      institutionalized persons over 65, drawn at random from the electoral roll, was
      given a standardized neurological and psychiatric examination based on DSM-IV
      criteria. The clinical examination also included an electrocardiogram (ECG) and a
      questionnaire relating to life-time medical history. Cardiac events were
      validated by the general practitioner. RESULTS: Within this general population
      sample the prevalence of suicide attempts was 3.9%. A significant positive
      association was observed between life-time prevalence of CAD and suicide attempts
      (p<0.04). Suicide attempts were associated with major depression (p<0.001) co
      morbid anxiety and depression (p<0.001) but not anxiety alone (p=0.16). A
      logistic regression analysis showed that the relationship between suicide
      attempts and CAD persists after adjustment for depression and anxiety.
      CONCLUSION: CAD is associated with suicidal behaviour independently of
      depression, however, longitudinal studies are required to clarify the direction
      of causality and to integrate genetic, biological, environmental and
      psychological factors into an aetiological model.

PMID- 16416466
TI  - A longitudinal study regarding conversion from mild memory impairment to dementia
      in a Japanese community.
AB  - OBJECTIVE: To estimate the rate that subjects with Mild Memory Impairment /Not
      Dementia (MMI/ND) shifted to dementia in a population-based cohort and to
      establish simple diagnostic methods for identification of high-risk persons for
      dementia. METHODS: Subjects in a community-based elderly cohort of MMI/ND were
      followed longitudinally. Subjects were selected from the participants in the
      first Nakayama study. MMI/ND was defined as memory deficit with objective memory
      assessment, without dementia, impairment of general cognitive function, or
      disability in activities of daily living. The conversion rate was calculated
      using the person-year method. RESULTS: At baseline, the sample consisted of 104
      subjects (59 female; 45 male) selected from 1,162 community dwellers aged over 65
      year. During the five-year follow-up, 14 subjects died, 13 moved to other
      communities, and six refused to participate further. Eleven (10.6%) subjects were
      diagnosed with Alzheimer's disease (AD), five (4.8%) were diagnosed with vascular
      dementia (VaD), and six (5.8%) were diagnosed with dementia of other etiology.
      The annual conversion rate that MMI/ND shifted to AD is calculated on 8.5% per
      100 person-year, and shifted to dementia on 16.1% per 100 person-year in this
      survey. CONCLUSIONS: The rate at which subjects with MMI/ND whose conditions
      shifted to dementia was the same as the rate that subjects with mild cognitive
      impairment (MCI) shifted to dementia in a previous report. It would be useful to
      identify groups of high-risk individuals for dementia by simple diagnostic
      methods.

PMID- 16416467
TI  - Use of an Italian version of the telephone interview for cognitive status in
      Alzheimer's disease.
AB  - OBJECTIVES: Validation of an Italian version of the Telephone Interview for
      Cognitive Status (I-TICS). METHODS: Telephone administration of the I-TICS within
      6 weeks of face-to-face testing with the Mini Mental State Examination (MMSE), in
      Probable Alzheimer's disease (AD) patients and healthy controls. Two hundred and
      seven consecutive outpatients with cognitive impairment were recruited from
      Dementia Clinic of University Campus BioMedico. Of these, 45 probable AD patients
      with complete data were analyzed. Other dementias, Mild Cognitive Impairment
      (MCI), and patients with incomplete data were excluded. The control sample
      consisted of 64 age- and sex-matched healthy subjects. For diagnosis, an
      extensive clinical evaluation, laboratory testing, brain imaging, EEG,
      neuropsychological battery and a depression scale were used. For I-TICS
      validation, telephone I-TICS and face-to-face MMSE were administered. RESULTS:
      The I-TICS correlated highly and linearly with the MMSE (Pearson's r=0.904).
      Conversion equations are provided. Sensitivity and specificity were similar
      between tests (area under curve=0.894 for the I-TICS; 0.966 for the MMSE). I-TICS
      sensitivity was 84% and specificity 86% at a cut-off score of 28. No significant
      difference in accuracy with the MMSE was present. Total agreement between I-TICS
      and MMSE was 'substantial' at 86% (Cohen's K=0.717). Repeated testing in a subset
      of patients showed a disease progression related decrease of 4.2 points/year
      (t=2.664; p=0.018) in I-TICS scores. CONCLUSION: The I-TICS is a valid instrument
      in clinical and research screening and monitoring of AD. Potential applications
      in other dementias and MCI are worth further studies.

PMID- 16416468
TI  - Depressive symptoms and white matter changes in patients with dementia.
AB  - OBJECTIVE: The aim of the present study was to investigate if depressive symptoms
      in demented patients are associated with white matter changes (WMCs) in the
      brain. BACKGROUND: WMCs are frequently found in patients with dementia, as well
      as among elderly nondemented patients with depressive symptoms. However, it is
      less established whether or not WMCs are related to depressive symptoms in
      demented patients. METHODS: 67 (26 men, 41 women) patients with primary
      degenerative dementia (Alzheimer's disease, frontotemporal dementia), vascular
      dementia (VaD), or mixed Alzheimer/VaD dementia were included in the study. The
      patients were young-old (mean 68.1, SD 7.3). All patients underwent a
      standardized examination procedure and MRI of the brain. The degree of WMCs was
      visually rated, blindly. Depressive symptoms were rated according to the
      Gottfries-Brane-Steen scale (anxiety, fear-panic, depressed mood). RESULTS: No
      significant relationship was found between WMCs and depressive symptoms in the
      demented patients. CONCLUSION: The possible involvement of WMCs in the
      pathogenesis of depressive symptoms in dementia is unclear. A link between
      disruptions of frontal-subcortical pathways, due to WMCs, and depressive
      symptomatology in dementia has been hypothesised from earlier findings, which
      would imply common elements of pathogenesis for depressive symptomatology and
      cognitive impairment in dementia. However, the results of the present study do
      not add further support to this hypothesis.

PMID- 16416469
TI  - Elderly suicide and the 2003 SARS epidemic in Hong Kong.
AB  - BACKGROUND: Hong Kong was struck by the community outbreak of Severe Acute
      Respiratory Syndrome (SARS) in 2003. In the same year, the elderly suicide rate
      in Hong Kong showed a sharp upturn from a previous downward trend. METHODS:
      Secondary analyses using Poisson Regression Models on the suicide statistics from
      the Census and Statistics Department of the Hong Kong Government were performed.
      RESULTS: In a Poisson Regression Model on the annual suicide rates in elders aged
      65 and over in years 1986-2003, 2002 served as the reference year. Suicide rates
      in 1986-1997 were significantly higher than the reference year, with an Incident
      Rate Ratio (IRR) of 1.34 to 1.61. However, rates in 1998-2001 did not differ from
      the reference year significantly, representing stabilization of suicide rates for
      4 years after 1997. The elderly suicide rate increased to 37.46/100,000 in 2003,
      with an IRR of 1.32 (p=0.0019) relative to 2002. Such trend is preserved when
      female elderly suicide rates in 1993-2003 were analyzed, while suicide rates in
      elderly men and younger age groups did not follow this pattern. DISCUSSIONS:
      Mechanistic factors such as breakdown of social network and limited access to
      health care might account for the findings. These factors could have potentiated
      biopsychosocial risk factors for suicide at individual levels, particularly in
      elderly. Female elders, by way of their previous readiness to utilize social and
      health services instituted in the past decade, are thus more susceptible to the
      effects of temporary suspension of these services during the SARS epidemic.
      CONCLUSIONS: The SARS epidemic was associated with increased risk of completed
      suicide in female elders, but not in male elders or the population under 65 years
      of age.

PMID- 16416470
TI  - Impairment of activities of daily living requiring memory or complex reasoning as
      part of the MCI syndrome.
AB  - BACKGROUND: Mild Cognitive Impairment (MCI) is a borderline state between age
      associated cognitive decline and mild dementia. MCI is separated from mild
      dementia by an absence of global intellectual deterioration and the preservation
      of activities of daily living (ADL). However, even mild degrees of cognitive
      deterioration are known to have negative effects on complex ADL. OBJECTIVES: To
      examine whether patients with MCI have impaired ADL as compared to healthy
      controls, which areas of ADL are particularly involved, and whether limitations
      on ADL are associated with demographical or clinical data. METHODS: Forty-eight
      patients with MCI diagnosed according to research criteria and 42 cognitively
      unimpaired controls were enrolled. Cognitive function was inter alia assessed by
      the MMSE, complex ADL by the ADCS-MCI-ADL scale. Frequency distributions were
      compared between patients and controls using chi-square tests. Mean values were
      examined for statistically significant differences using Kruskal-Wallis tests. A
      Bonferroni correction for multiple comparisons was applied to the comparison of
      the 18 areas of the ADCS-MCI-ADL scale. Associations between ADL and biographical
      or clinical data were analysed using non-parametric correlations. RESULTS: The
      overall score on the ADCS-MCI-ADL scale was significantly lower in the MCI group.
      Patients performed significantly worse on 14 out of 18 activities. Activities
      involving memory or complex reasoning were particularly impaired, whereas more
      basic activities were unimpaired. There were no statistically significant
      associations of the ADCS-MCI-ADL overall score with age, years of formal
      education, gender, or number of cognitive domains affected in the group of MCI
      patients. However, there was a statistically significant association between the
      ADCS-MCI-ADL and the MMSE score. CONCLUSION: MCI patients may be impaired in
      complex ADL.

PMID- 16416473
TI  - Prehospital administration of enoxaparin before primary angioplasty for ST
      elevation acute myocardial infarction.
AB  - We hypothesized that primary percutaneous coronary intervention (PCI) could be
      performed with prehospital injections of enoxaparin for ST segment elevation
      myocardial infarction (STEMI). Enoxaparin has been studied in combination with
      fibrinolysis in STEMI, but has not been evaluated as anticoagulant regimen for
      primary PCI. In a prospective registry, 143 consecutive patients with STEMI
      received prehospital 0.5 mg/kg intravenous (i.v.) bolus followed by 1 mg/kg
      subcutaneous enoxaparin before immediate transport for PCI. We focused on anti-Xa
      activities before and after PCI, bleedings, infarct-related artery patency, and
      major adverse cardiac events at day 30. Anti-Xa activity was at the target level
      (>0.5 IU/ml) in 99% of patients during PCI, and in 100% 4 hr after injections;
      over-anticoagulation (>1.5 IU/ml) was noted in 9 and 2%, respectively at start
      and 4 hr after injections. Bleeding complications with enoxaparin were rare:
      major in 1.4% (no intracranial hemorrhages), minor in 2.1%. A patent infarct
      related artery (TIMI 2 + 3) was observed in 40.6% of the patients before PCI.
      TIMI 3 flow was obtained in 88.1% of the cases after PCI. Major adverse cardiac
      events at 30 days occurred in 5.6% of cases: death 2.8%, reinfarction 3.5%, and
      target lesion revascularisation 3.5%. Prehospital i.v. and subcutaneous
      enoxaparin provides simple and rapid anticoagulation for PCI in STEMI patients.
      Enoxaparin dose needs to be reduced regarding the 9% of over-anticoagulation.
      This study suggests the potential of enoxaparin as an alternative anticoagulant
      regimen for primary PCI.

PMID- 16416471
TI  - Assessing quality of life in Taiwanese patients with Alzheimer's disease.
AB  - OBJECTIVE: To measure differences in patients with Alzheimer's disease (AD) and
      caregiver assessments of the patients' quality of life (QOL) and to identify the
      patient characteristics, caregiver characteristics, or patient-caregiver
      interactions responsible for these differences. METHODS: We recruited consecutive
      patients with AD and their caregivers from an outpatient clinic of a teaching
      hospital in Taiwan. Each patient and caregiver rated the patient's quality of
      life (QOL) using the Quality of Life-Alzheimer's Disease (QOL-AD) questionnaire.
      Additional measures included the Mini-Mental State Examination (MMSE), Clinical
      Dementia Rating, Blessed Activities of Daily Living assessment, and the
      Neuropsychiatric Inventory. Only patients with MMSE score >or= 10 were enrolled.
      RESULTS: Of the 94 patients enrolled, 81 with reliable caregivers were included.
      The internal consistency was good within both patient and caregiver reports
      (alpha=0.83 and 0.79, respectively). The agreement between patient and caregiver
      QOL-AD reports was moderate (absolute intraclass correlation coefficient: 0.41).
      Regression analyses indicated that caregiver distress was the most consistent
      predictor of QOL rating discrepancy between the patient and caregiver, and
      patient depressive disorder was the most significant predictor of QOL.
      CONCLUSIONS: Similar to previous studies in different ethnic groups, the QOL
      perception differed between the Taiwanese patients with AD and their caregivers.
      Medical professionals should be cautious if they try to use a caregiver-reported
      QOL to replace the patient-reported QOL among AD patients of mild to moderate
      severity.

PMID- 16416474
TI  - Percutaneous closure of atrial septal defect type ostium secundum using the new
      Intrasept occluder: initial experience.
AB  - We report the first experience obtained with the new Intrasept device. We
      attempted to treat 35 patients with a mean age of 43 +/- 21 years. The mean size
      of the defect was 17/15 mm. It was successfully closed in 31 patients. In the
      remaining four the device could not be stabilized because of excessive defect
      size. A small residual shunt was present immediately following implantation in
      three patients. No complications occurred during the procedure and at 6 months,
      31 patients had an uneventful outcome. Only one patient had a small residual
      shunt. No thrombus, embolization, or device fracture was documented during a mean
      follow-up of 17 +/- 11 months. Percutaneous closure of ASD ostium secundum is
      feasible with the Intrasept device with a high success rate and very good medium
      term outcome. Our initial experience and results were excellent with small to
      medium size defects, however, large defects (>20 mm) remain challenging.

PMID- 16416475
TI  - The impact of interventional cardiology for the management of adults with
      congenital heart defects.
AB  - The objective of this study is to assess the impact of interventional cardiology
      procedures for the management of ACHD. The interventional approach to the
      management of CHD in the adult population is becoming increasingly recognized as
      the preferred treatment option for a wide number of congenital cardiac
      conditions. The files of all consecutive patients over 18 years of age who were
      hospitalized in our department from January 2000 to December 2004 were reviewed.
      Over the study period, 1,115 ACHD (583 women; mean age 41 +/- 13.8, years, range
      18-72 years) were hospitalized in our department; 752 patients underwent cardiac
      catheterization and 82.4% of them had an interventional procedure carried out.
      ASD (329/620) and PFO (159/620) closure account for 78% of all the procedures
      carried out, with a 2.7% of major complications incidence (all of them closing
      ASDs). Other procedures such as stenting aortic coarctation (40/620), ventricular
      septal defect closure (33/620), patent ductus arteriosus embolization (30/620),
      pulmonary valvuloplasty (12/620), stenting pulmonary artery branches (8/620), etc
      (5/620) were carried out. The most important complication was one death, which
      occurred in the case of a 22-year-old woman after stent implantation for a
      recurrent aortic coarctation. A trivial residual shunt was detected in only 5% of
      the patients who had a 6-month follow-up after VSD closure; no residual shunt was
      found after PDA embolization during the 12-month follow-up. In conclusion, we
      believe that the interventional approach is a safe and successful treatment
      option for a wide number of congenital cardiac conditions. The increasing use of
      catheter interventions for these patients will be responsible for an increase of
      complex cases in surgery.

PMID- 16416476
TI  - Tea, obesity, and diabetes.
AB  - Tea has been found to possess widespread biological functions based on a variety
      of laboratory data. The effects of tea on obesity and diabetes have received
      increasing attention. This paper reviews the evidence for the connections among
      tea catechins, and obesity and diabetes. Tea catechins, especially (-)
      epigallocatechin gallate (EGCG), appear to have antiobesity and antidiabetic
      effects. While few epidemiological and clinical studies show the health benefits
      of EGCG on obesity and diabetes, the mechanisms of its actions are emerging based
      on the various laboratory data. These mechanisms may be related to certain
      pathways, such as through the modulations of energy balance, endocrine systems,
      food intake, lipid and carbohydrate metabolism, the redox status, and activities
      of different types of cells (i. e., fat, liver, muscle, and beta-pancreatic
      cells). Because the EGCG receptor, the so-called 67-kDa laminin receptor (LR),
      has been discovered with colocalization of other types of LR and cytoskeleton in
      both cancer cells and normal cells, this may explain that EGCG possesses numerous
      actions. The mechanistic results of this review may possibly be utilized in the
      treatment of obesity, diabetes, and other related diseases using tea- and EGCG
      based folk medicines.

PMID- 16416477
TI  - Di- and tridysprosium endohedral metallofullerenes with cages from C94 to C100.

PMID- 16416478
TI  - Structural investigation of cisplatin-protein interactions: selective platination
      of His19 in a cuprozinc superoxide dismutase.

PMID- 16416479
TI  - Correlation of metal spin state with catalytic reactivity: polymerizations
      mediated by alpha-diimine-iron complexes.

PMID- 16416480
TI  - Synthesis, stability, and surface plasmonic properties of rhodium multipods, and
      their use as substrates for surface-enhanced Raman scattering.

PMID- 16416481
TI  - Straightforward one-pot synthesis of trifluoromethyl sulfonium salts.

PMID- 16416482
TI  - Chemoselective amide ligations by decarboxylative condensations of N
      alkylhydroxylamines and alpha-ketoacids.

PMID- 16416483
TI  - Primary-amine-specific lactamization of omega-amino acids by an artificial
      cyclotransferase based on [18]crown-6.

PMID- 16416484
TI  - Cathodic electrochemiluminescence of acetonitrile, acetonitrile-1,10
      phenanthroline and acetonitrile-ternary Eu(III) complexes at a gold electrode.
AB  - Cathodic electrochemiluminescence (ECL) behaviours of the acetonitrile,
      acetonitrile-1,10-phenanthroline (phen) and acetonitrile-ternary Eu(III) complex
      systems at a gold electrode were studied. One very weak cathodic ECL-2 at -3.5 V
      was observed in 0.1 mol/L tetrabutylammonium tetrafluoroborate (TBABF(4))
      acetonitrile solution. When 10 mmol/L tetrabutylammonium peroxydisulphate
      [(TBA)(2)S(2)O(8)] was added to 0.1 mol/L TBABF(4) acetonitrile solution, another
      cathodic ECL-1 at -2.7 V appeared and the potential for ECL-2 was shifted from 
      3.5 to -3.1 V. Furthermore, ECL-2 intensity was enhanced about 20-fold. When 1 x
      10(-4) mol/L phen was added to 0.1 mol/L TBABF(4) + 10 mmol/L (TBA)(2)S(2)O(8)
      acetonitrile solution, the ECL intensities of ECL-1 and ECL-2 were enhanced about
      20-fold compared with those of 0.1 mol/L TBABF(4) + 10 mmol/L (TBA)(2)S(2)O(8)
      acetonitrile solution. The maximum emission peaks of ECL-1 and ECL-2 in the three
      systems mentioned above appeared at about 530 nm. The products obtained by
      electrolysing 0.1 mol/L TBABF(4) acetonitrile solution at -3.5 V for 20 min were
      analysed by Fourier Transform Infrared (FTIR) spectra and gas chromatography-mass
      spectrometry (GC-MS) and the emitter of ECL-1 and ECL-2 was identified as excited
      state polyacetonitrile. When ternary Eu(III) complexes were presented in 0.1
      mol/L TBABF(4) + 10 mmol/L (TBA)(2)S(2)O(8) acetonitrile solution, another
      maximum emission peak with a narrow band centred at about 610 nm appeared in ECL
      1 in addition to the maximum emission peaks at about 530 nm for ECL-1 and ECL-2.
      The emitter of ECL emission at 610 nm was identified as the excited states
      Eu(III)*. The mechanisms for cathodic ECL behaviours of the acetonitrile,
      acetonitrile-phen and acetonitrile-ternary Eu(III) complex systems at a gold
      electrode have been proposed. The extremely sharp emission bands for ternary
      Eu(III) complexes may have analytical potential.

PMID- 16416485
TI  - Anti-oxidant and pro-oxidant behaviour of bucillamine.
AB  - Bucillamine (BUC) is used clinically for the treatment of rheumatoid arthritis.
      Some of the pharmacological action of BUC has been reported as being dependent on
      the production of reactive oxygen species (ROS). In this paper the reactivity of
      BUC with superoxide anion radical (O(2) (*-)) generated from potassium
      superoxide/18-crown-6 ether dissolved in DMSO, hydroxyl radical (HO(*)) produced
      in the Cu(2+)-H(2)O(2) reaction, peroxyl radical (ROO(*)) from 2,2'-azobis (2
      amidino-propane) dichloride decomposition, and singlet oxygen ((1)O(2)) from a
      mixture of alkaline aqueous H(2)O(2) and acetonitrile, have been investigated.
      Chemiluminescence, fluorescence, electron paramagnetic resonance (EPR) spin
      trapping techniques and the deoxyribose and oxygen radical absorbance capacity
      towards ROO(*) (ORAC(ROO)) assays were used to elucidate the anti- and pro
      oxidative behaviours of BUC towards ROS. The results indicated that BUC
      efficiently inhibited chemiluminescence from the O(2) (*-)-generating system at
      relatively high concentrations (0.5-2 mmol/L); however, at lower concentrations
      (<0.5 mmol/L) the drug enhanced light emission. The behaviour of BUC was
      correlated with a capacity to decrease the chemiluminescence signal from the
      Cu(2+)-H(2)O(2) system; scavenging HO(*) was effective only at high
      concentrations (1-2 mmol/L) of the drug. Bucillamine also prevented deoxyribose
      degradation induced by HO(*) in a dose-dependent manner, reaching maximal
      inhibition (24.5%) at a relative high concentration (1.54 mmol/L). Moreover, BUC
      reacts with ROO(*); the relative ORAC(ROO) was found to be 0.34 micromol/L Trolox
      equivalents/micromol sample. The drug showed quenching of (1)O(2)-dependent
      2,2,6,6-tetramethylpiperidine-N-oxide radical formation from 2,2,6,6-tetramethyl
      piperidine (e.g. 90% inhibition was found at 1 mmol/L concentration). The results
      showed that BUC may directly scavenge ROS or inhibit reactions generating them.
      However, the drug may have pro-oxidant activity under some reaction conditions.

PMID- 16416486
TI  - The influence of preparation conditions on the fluorescence properties of
      Eu(Sal)(3)Phen.
AB  - The influence of the synthesis conditions (method and sequence of adding
      reagents, reaction temperature, stirring rate) on the luminescence performance of
      the rare earth ternary complex compound europium-salicylic acid-(1,10
      phenanthroline) [Eu(Sal)(3)Phen] was studied. We show that the method and
      sequence of adding reagents greatly affects the luminescence properties of the
      products. Within the range of synthesis temperatures (30-70 degrees C), the
      complex has a better luminescence performance at the lower temperature. However,
      performance decreased when the temperature decreased to 20 degrees C. Increase of
      stirring rate led to better performance in the range 200-700 r.p.m. Infrared (IR)
      spectroscopy, scanning electron microscopy (SEM) and wide-angle X-ray diffraction
      (WAXD) were utilized to characterize the structure and morphology of
      Eu(Sal)(3)Phen. The studies demonstrate that the crystallization of the product
      increased with increasing luminescence of the product. Therefore, it is proposed
      that increasing the crystallization of the product will enhance its luminescence
      performance.

PMID- 16416487
TI  - Bioluminescent monitoring of turbulent bioconvection.
AB  - Under adjusted experimental conditions, open-to-air cultures of lux gene
      engineered Ralstonia eutropha (wholecell biosensors of copper) exhibit
      bioconvection, which accounts for fluctuating bioluminescence. The power spectrum
      of bioluminescence intensity fluctuations recorded from a cylindrical sample 9 mm
      in diameter and approximately 10 mm in height is characterized by a dominant low
      frequency oscillation (with a characteristic period of approximately 8-12 min),
      which is occasionally accompanied by a few weaker oscillations. The corresponding
      spectral peaks emerge on a high-noise background. The spectra of bioluminescence
      intensity fluctuations qualitatively resemble the spectra of temperature or fluid
      velocity fluctuations in an appropriate turbulent thermal convection system. It
      has been suggested that in a bioconvective system, like in thermal convection
      systems, the emergence of oscillation reflects the large-scale convective
      circulation that spans the height of the cylindrical cell. The velocity of large
      scale bioconvective circulation was estimated to be 37-48 microm/s. The
      occasional emergence of weaker-than-dominant oscillations was explained through
      the coexistence and interaction of the large-scale circulation with, presumably,
      a gene-expression-related cyclic process (with a characteristic period of
      approximately 25-50 min).

PMID- 16416488
TI  - Effect of the solvent on the conformation of a depsipeptide: NMR-derived solution
      structure of hormaomycin in DMSO from residual dipolar couplings in a novel DMSO
      compatible alignment medium.
AB  - The macrocyclic compound hormaomycin has been investigated by NMR spectroscopy
      and by restrained molecular-dynamics simulations. Measurement of residual dipolar
      couplings induced by dissolving the depsipeptide in a polyacrylamide gel
      compatible with DMSO and their incorporation into the structure calculation of
      the title compound improved the precision of the family of structures. In DMSO
      the macrocyclic ring shows two beta-turns, whose positions in the sequence differ
      from those found in the CDCl3 solution structure and in the crystal structure
      obtained from hexylene glycol/H2O (50:50). The bulky side chain consisting of a 3
      (2-nitrocyclopropyl)alanine and a chlorinated N-hydroxypyrrole moiety is flexible
      in DMSO.

PMID- 16416489
TI  - omega-Hydrazino linear polyethylenimine: a monoconjugation building block for
      nucleic acid delivery.
AB  - Nonviral gene therapy requires efficient vectors that are able to deliver nucleic
      acids inside the targeted cell nucleus. Developing new tools for the synthesis of
      supramolecular vectors with improved transfection efficiency and better
      biodistribution is therefore a crucial issue. Here we describe the synthesis of a
      140-mer linear polyethylenimine (L-PEI) terminated at one end by a highly
      nucleophilic hydrazine residue. This cationic polymer, whose backbone is well
      known for its remarkable gene-delivery efficiency, constitutes a building block
      for omega-regioselective conjugation to molecules through the formation of stable
      linkages such as the hydrazone bonds. To demonstrate the potential of the omega
      hydrazino linear polyethylenimine, human serum transferrin, a ligand that is well
      know to improve gene-delivery systems, was used as a model of sensitive material.
      The blood protein was oxidized to generate an aldehyde function and was
      subsequently conjugated to hydrazino PEI. The new polyethylenimine-transferrin
      (PEI-Tf) vector was purified and was shown to condense plasmid DNA into compact
      superstructures compatible with cellular uptake. Finally, the cellular-binding
      and gene-delivery properties of PEI/DNA polyplexes incorporating different
      quantities of transferrin were evaluated by FACS analysis and luciferase assay.

PMID- 16416490
TI  - Identification of new acceptor specificities of glycosyltransferase R with the
      aid of substrate microarrays.
AB  - Finding opportunities to construct sugar motifs and to transfer them to targets
      of biological relevance and rapid identification of glycosylation events are
      important goals for glycobiology and a field of increasing interest. Here we have
      applied an enzyme microarray screening system for the identification of new
      acceptor specificities of the glycosyltransferase R (GTFR) from Streptococcus
      oralis (E.C. 2.4.1.5), which was able to effect the synthesis of sugar motifs in
      short times and with low amounts of substrate. These observations resulted in the
      development of a convenient alpha-glycosylation by the non-Leloir
      glycosyltransferase GTFR, with sucrose as substrate and with different alcohols
      and amino acid derivatives as acceptors, for the synthesis of glycoethers and
      glycosylated amino acids not observed with the use of familiar GTFs with high
      sequence homology.

PMID- 16416491
TI  - Effect of alkali metal coordination on gas-phase chemistry of the diphosphate
      ion: the MH(2)P(2)O(7) (-) ions.
AB  - Systematic experimental and theoretical studies on anionic phosphate species in
      the gas phase are almost nonexistent, even though they could provide a benchmark
      for enhanced comprehension of their liquid-phase chemical behavior. Gaseous
      MH(2)P(2)O(7) (-) ions (M=Li, Na, K, Rb, Cs), obtained from electrospray
      ionization of solutions containing H(4)P(2)O(7) and MOH or M salts as a source of
      M(+) ions were structurally assayed by collisionally activated dissociation (CAD)
      mass spectrometry and theoretical calculations at the B3LYP/6-31+G* level of
      theory. The joint application of mass spectrometric techniques and theoretical
      methods allowed the MH(2)P(2)O(7) (-) ions to be identified as having a structure
      in which the linear diphosphate anion is coordinated to the M(+) ion (I) and
      provides information on gas-phase isomerization processes in the
      [PO(3)...MH(2)PO(4)](-) clusters II and the [P(2)O(6)...M...H(2)O](-) clusters
      IV. Studies of gas-phase reactivity by Fourier transform ion cyclotron resonance
      (FTICR) and triple quadrupole (TQ) mass spectrometry revealed that the
      MH(2)P(2)O(7) (-) ions react with selected nucleophiles by clustering, proton
      transfer and addition-elimination mechanisms. The influence of the coordination
      of alkali metal ions on the chemical behavior of pyrophosphate is discussed.

PMID- 16416492
TI  - Scope and mechanism of the Pd(II)-catalyzed arylation/carboalkoxylation of
      unactivated olefins with indoles.
AB  - Treatment of 1-methyl-2-(4-pentenyl)indole (5) with a catalytic amount of
      [PdCl2(MeCN)2] (2; 5 mol %) and a stoichiometric amount of CuCl2 (3 equiv) in
      methanol under CO (1 atm) at room temperature for 30 min gives methyl (9-methyl
      2,3,4,9-tetrahydro-4-carbazolyl)acetate (6), which was isolated in 83% yield. A
      number of 2- and 3-alkenyl indoles undergo a similar palladium-catalyzed
      cyclization/carboalkoxylation to give the corresponding polycyclic indole
      derivatives in moderate to excellent yields with excellent regio- and
      diastereoselectivity. Under similar conditions, vinyl arenes undergo
      intermolecular arylation/carboalkoxylation with indoles to give 3-(1-aryl-2
      carbomethoxyethyl) indoles in moderate yield with high regioselectivity.
      Stereochemical analyses of the palladium-catalyzed cyclization/carboalkoxylation
      of both 2- and 3-alkenyl indoles are in agreement with mechanisms involving outer
      sphere attack of the indole on a palladium-olefin complex followed by alpha
      migratory insertion of CO and methanolysis of the resulting acyl palladium
      intermediate. CuCl2 functions as the terminal oxidant in this palladium-catalyzed
      cyclization/carboalkoxylation of alkenyl indoles and also significantly increases
      the rate of reaction of 2 with the alkenyl indole to form the corresponding acyl
      palladium complex. Spectroscopic studies are in agreement with the intermediacy
      of a heterobimetallic Pd/Cu complex as the active catalyst in this reaction.

PMID- 16416493
TI  - Atropisomeric discrimination in new Ru(II) complexes containing the C(2)
      symmetric didentate chiral phenyl-1,2-bisoxazolinic ligand.
AB  - A new family of Ru(II) complexes containing the tridentate meridional 2,2':6',2''
      terpyridine (trpy) ligand, a C(2)-symmetric didentate chiral oxazolinic ligand
      1,2-bis[4'-alkyl-4',5'-dihydro-2'-oxazolyl]benzene (Phbox-R, R = Et or iPr), and
      a monodentate ligand, of general formula [Ru(Y)(trpy)(Phbox-R)](n+) (Y = Cl,
      H(2)O, py, MeCN, or 2-OH-py (2-hydroxypyridine)) have been prepared and
      thoroughly characterized. In the solid state the complexes have been
      characterized by IR spectroscopy and by X-ray diffraction analysis in two cases.
      In solution, UV/Vis, cyclic voltammetry (CV), and one-dimensional (1D) and two
      dimensional (2D) NMR spectroscopy techniques have been used. We have also
      performed density functional theory (DFT) calculations with these complexes to
      interpret and complement experimental results. The oxazolinic ligand Phbox-R
      exhibits free rotation along the phenyloxazoline axes. Upon coordination this
      rotation is restricted by an energy barrier of 26.0 kcal mol(-1) for the case of
      [Ru(trpy)(Phbox-iPr)(MeCN)](2+) thus preventing its potential interconversion.
      Furthermore due to steric effects the two atropisomers differ in energy by 5.7
      kcal mol(-1) and as a consequence only one of them is obtained in the synthesis.
      Subtle but important structural effects occur upon changing the monodentate
      ligands that are detected by NMR spectroscopy in solution and interpreted by
      using their calculated DFT structures.

PMID- 16416495
TI  - A novel method for time-resolved fluorimetric determination and imaging of the
      activity of peroxidase, and its application to an enzyme-linked immunosorbent
      assay.
AB  - A new type of fluorescence assay for the determination of peroxidase (POx)
      activity is presented. The assay is based on the indication of the enzymatic
      consumption of H(2)O(2) (HP), using a fluorescent europium-tetracycline (Eu(3)TC)
      complex as indicator. On addition of HP, this complex forms a highly fluorescent
      adduct (Eu(3)TC-HP), which is decomposed in the presence of POx to form the
      weakly fluorescent europium-tetracycline (Eu(3)TC). Hence, the activity of the
      enzyme can be directly determined by means of the luminescent Eu(3)TC complex as
      indicator. The POx assay demonstrated herein was elaborated starting from a
      spectral characterization of the complex systems involved. Due to the long
      lifetime of lanthanide luminescence, both steady-state and time-resolved
      luminescence assays can easily be performed. The time-resolved assay can quantify
      POx in the range from 4.0 x 10(-5) to 5.9 x 10(-3) U mL(-1), with a limit of
      detection of 1.0 x 10(-5) U mL(-1). The effects of POx inhibitors such as
      cyanide, hydroxylamine, and azide have also been studied. In addition, a time
      resolved fluorescent detection method for a POx-based enzyme-linked immunosorbent
      assay (ELISA) has been developed, which is demonstrated in a sandwich model assay
      with bovine IgG serving as analyte. Furthermore, a time-resolved fluorescent
      imaging method is demonstrated that makes use of a straightforward imaging set-up
      adjusted to the optical properties of the europium reagent.

PMID- 16416494
TI  - Noncovalent synthesis in aqueous solution and spectroscopic characterization of
      multi-porphyrin complexes.
AB  - The interactions of the tetracationic meso-tetrakis(N-methyl-4-pyridyl)porphyrin
      (H(2)TMPyP) and its metallo derivatives (MTMPyP) (where M=copper(II), zinc(II),
      and gold(III) with the octa-anionic form (at neutral pH) of 5,11,17,23
      tetrasulfonato-25,26,27,28-tetrakis(hydroxycarbonylmethoxy)calix[4]arene
      (C(4)TsTc) lead to a series of complex species whose stoichiometry and porphyrin
      sequence can be easily tuned. Crystallographic, spectroscopic, and diffusion NMR
      studies converge towards a common picture in which a central 1:4
      porphyrin/calixarene unit serves as a template for the formation of more complex
      species. These species arise by successive, stepwise addition of single porphyrin
      molecules above and below the plane of the 1:4 central core to ultimately give a
      7:4 complex. Noticeably, the stoichiometry of the various complex species
      corresponds to the actual concentration ratio of porphyrins and calixarenes in
      solution allowing the stoichiometry of these species to be easily tuned. This
      behavior and the remarkable stability of these species allow homo-porphyrin and
      hetero-(metallo)porphyrin species to be formed with control of not only the
      stoichiometry but also the sequence of the porphyrin array. The flexibility and
      ease of this approach permit, in principle, the design and synthesis of porphyrin
      arrays for predetermined purposes. For example, we have shown that it is very
      easy to design and obtain mixed porphyrin species in which a foreseen
      photoinduced electron-transfer is indeed observed.

PMID- 16416496
TI  - Competition of proton and electron transfers in gas-phase reactions of hydrogen
      containing dications CHX2+ (X = F, Cl, Br, I) with atoms, nonpolar and polar
      molecules.
AB  - The competition between proton and electron transfer in reactions of mass
      selected dications CHX2+ (X = F, Cl, Br, and I) with rare gas atoms (Ne, Ar, Kr,
      and Xe) and selected molecular reagents (N2, O2, CO, H2O, and HCl) is studied in
      the gas phase. In the ion-molecule reactions of CHX2+ dications with atoms and
      nonpolar molecules, it is the energy balance of electron transfer that acts as
      the decisive factor: when the exothermicity of electron transfer exceeds 2 eV,
      this process predominates at the expense of bond-forming proton transfer. In
      marked contrast, the reactions between these triatomic dications and polar
      molecules are governed for the benefit of the thermochemically more favored
      products resulting from proton transfer.

PMID- 16416497
TI  - Towards polyoxometalate-integrated nanosystems.
AB  - Polyoxometalates represent a diverse range of molecular clusters with an almost
      unmatched range of physical properties and the ability to form structures that
      can bridge several length scales. The new building block principles that have
      been discovered are beginning to allow the design of complex clusters with
      desired properties and structures; several structural types and novel physical
      properties are examined herein. The overall message that is presented throughout
      is the possibility that polyoxometalate clusters could be excellent candidates to
      be exploited in the development of functional nanosystems or nanodevices. The
      concepts that underpin the development of nanoscale devices are discussed
      briefly, as are the considerable challenges that must be overcome to realise
      polyoxometalate-based functional nanosystems.

PMID- 16416499
TI  - Can substituted cyclopentadiene become aromatic or antiaromatic?
AB  - Cyclopentadiene derivatives with electronegative (F, Cl) or electropositive
      (H(3)Si, Me(3)Si) bis-5,5-substituents were studied at the B3LYP/6-311G* level of
      theory. It was found that there is no special stabilization or destabilization
      for any of the derivatives; the energetic effects that were previously attributed
      to aromatic stabilization or antiaromatic destabilization are the result of
      interactions in the reference systems. A nucleus-independent chemical shift
      (NICS) scan study at the HF-GIAO/6-311+G* theoretical level of these and similar
      derivatives suggest that they all show different magnitudes of diamagnetic ring
      current. None of the derivatives shows a paramagnetic ring current. Thus,
      cyclopentadienes are neither aromatic nor antiaromatic. It is also concluded that
      a diamagnetic ring current is perhaps necessary but certainly not a sufficient
      condition for aromaticity. The NICS scan procedure describes the type of ring
      current in the system, whereas a single isotropic NICS value (i.e., NICS(1)) may
      wrongly assign the type of ring current. It is shown that neither NICS(1) nor the
      NICS scan procedure can be used as a single aromaticity criterion.

PMID- 16416498
TI  - Micelle-to-vesicle transition induced by organic additives in catanionic
      surfactant systems.
AB  - A micelle-to-vesicle transition (MVT) induced by the addition of a series of
      apolar hydrocarbons (n-butylbenzene, n-hexane, n-octane, and n-dodecane) to the
      catanionic surfactant system n-dodecyltriethylammonium bromide/sodium n
      dodecylsulfate (DTEAB/SDS) has been investigated for the first time by means of
      rheology and turbidity measurements, dynamic light scattering (DLS), and
      transmission electron microscopy (TEM). Interestingly, a MVT can take place
      within certain micellar regions, which are dependent on the structure and chain
      length of the hydrocarbon. However, these hydrocarbons are unable to induce a MVT
      in another catanionic surfactant system, namely, n-dodecyltriethylammonium
      bromide/sodium n-dodecylsulfonate (DTEAB/SDSO(3)), in which the molecular
      interactions are weaker than in the DTEAB/SDS system. On the other hand, polar
      additives, such as n-octanol and n-octylamine, exhibit much higher efficiency and
      activity in inducing MVT than hydrocarbons in both DETAB/SDS and DTEAB/SDSO(3).
      Moreover, DLS, TEM, and time-resolved fluorescence quenching (TRFQ) results
      demonstrate that the ratio of vesicles to micelles in the system can be actively
      controlled by addition of polar additives. Possible mechanisms for the above
      phenomena are presented, and the potential application of controllable
      micelle/vesicle systems in the synthesis of tailored bimodal mesoporous materials
      is discussed.

PMID- 16416500
TI  - Optical processing with photochromic switches.
AB  - The absorbance, fluorescence, and refractive index of a photochromic material can
      be modulated under the influence of optical stimulations. The reversible
      modification of these macroscopic properties is a result of photoinduced
      transformations at the molecular level. These processes can be exploited to
      mediate the interplay of optical signals and offer the opportunity to design and
      implement photonic devices for optical processing based on molecular components.

PMID- 16416501
TI  - Synthesis of fullerene adducts with terpyridyl- or pyridylpyrrolidine groups in
      trans-1 positions.
AB  - Two C(60) hexakis-adducts (2 and 3) were synthesized by using a protection
      deprotection strategy. The symmetric fullerene tetrakis-adduct 8 was obtained by
      anthracene removal from the hexakis-adduct 7. Reaction of 8 with
      terpyridylglycine or pyridylglycine afforded two hexakis-adducts, 2 and 3. By
      using the retro-cyclopropanation reaction, the four malonate addends located on
      the equatorial belt of the hexakis-adducts were removed to afford two trans-1 bis
      adducts, 4 and 5, with terpyridyl- or pyridylpyrrolidine groups. The structures
      of 2 and 3 were confirmed by matrix-assisted laser desorption ionization time-of
      flight (MALDI-TOF) mass spectrometry, and (1)H, (13)C, and COSY NMR, and UV
      visible spectroscopy. The cyclic voltammograms of fullerene multiadducts 2, 3,
      and 9 show irreversible reductions. Self-assembled monolayers (SAMs) of 1 and 3
      were formed on gold surfaces through nitrogen adsorption. SAMs of 3 represent the
      first example of a fullerene hexakis-adduct formed on gold surfaces through
      nitrogen adsorption. Controlled potential electrolyses (CPE) were conducted to
      prepare trans-1 bis-adducts 4 and 5 modified with terpyridyl and pyridyl groups.

PMID- 16416502
TI  - Manganese-substituted carbonic anhydrase as a new peroxidase.
AB  - Carbonic anhydrase is a zinc metalloenzyme that catalyzes the hydration of carbon
      dioxide to bicarbonate. Replacing the active-site zinc with manganese yielded
      manganese-substituted carbonic anhydrase (CA[Mn]), which shows peroxidase
      activity with a bicarbonate-dependent mechanism. In the presence of bicarbonate
      and hydrogen peroxide, (CA[Mn]) catalyzed the efficient oxidation of o
      dianisidine with kcat/KM=1.4 x 10(6) m(-1) s(-1), which is comparable to that for
      horseradish peroxidase, kcat/KM=57 x 10(6) m(-1) s(-1). CA[Mn] also catalyzed the
      moderately enantioselective epoxidation of olefins to epoxides (E=5 for p
      chlorostyrene) in the presence of an amino-alcohol buffer, such as N,N-bis(2
      hydroxyethyl)-2-aminoethanesulfonic acid (BES). This enantioselectivity is
      similar to that for natural heme-based peroxidases, but has the advantage that
      CA[Mn] avoids the formation of aldehyde side products. CA[Mn] degrades during the
      epoxidation limiting the yield of the epoxidations to <12 %. Replacement of
      active-site residues Asn62, His64, Asn67, Gln92, or Thr200 with alanine by site
      directed mutagenesis decreased the enantioselectivity demonstrating that the
      active site controls the enantioselectivity of the epoxidation.

PMID- 16416503
TI  - Profiling in vitro drug release from subcutaneous implants: a review of current
      status and potential implications on drug product development.
AB  - This review presents current methods and strategies for studying the release
      characteristics of drugs from subcutaneous implant dosage forms. Implants are
      dosage forms that are subcutaneously placed with the aid of surgery or a
      hypodermic needle, and are designed to release drugs over a prolonged period of
      time. In most cases, the objective of a release test is to identify sufficiently
      discriminatory procedures that in turn would provide data to set meaningful
      specifications. Additional information obtained from successful in vitro-in vivo
      correlations (IVIVC) and accelerated drug release tests are extremely useful
      during drug product development. Although several workers have employed different
      methods to monitor drug release from these dosage forms, the use of the
      compendial Apparatus 4 (flow-through) device has been recommended in a
      publication on FIP/AAPS Guidelines for drug release testing of modified release
      dosage forms. However, most of method development with this device has focused on
      oral immediate or controlled release dosage forms and little published
      information is available on implants. Two recent reports on workshops provide
      useful information on methods to evaluate drug release from controlled-release
      parenterals such as implants, including IVIVC and accelerated release testing.
      Details on such studies, however, are generally not found in the literature;
      possibly because of the high proprietary value of methodologies for establishing
      release specifications of implant dosage forms. This article reviews the current
      status of methodologies used in the investigation of drug release from
      subcutaneous implants with an emphasis on mechanistic, product development and
      regulatory perspectives.

PMID- 16416504
TI  - Determination of tetracycline, chlortetracycline and oxytetracycline by flow
      injection with inhibitory chemiluminescence detection using copper(II) as a probe
      ion.
AB  - This paper reports an indirect flow-injection (FI) method for the determination
      of the tetracycline drugs (TCs), tetracycline (TC), chlortetracycline (CTC) and
      oxytetracycline (OTC), using copper(II) as a probe ion. The method was based on
      the inhibition caused by these TCs to the copper(II)-catalysed chemiluminescence
      (CL) reaction between luminol and H(2)O(2). The CL reaction was induced on-line
      and injection of the sample produced negative peaks as a result of the copper(II)
      complexation or displacement by the analytes. The height of the peaks was
      proportional to the drug concentration in the sample. The choice of the catalyst
      ion, the concentration of luminol, H(2)O(2) and copper(II) are discussed. The
      linear range was 3.6 x 10(-8)-1.0 x 10(-5), 1.1 x 10(-7)-1.0 x 10(-5) and 1.9 x
      10(-7)-1.0 x 10(-5) mol/L for TC, CTC and OTC, respectively. The detection limit
      was 5.0 x 10(-9) mol/L for TC, 1.0 x 10(-8) mol/L for CTC and 2.0 x 10(-8) mol/L
      for OTC (3sigma), respectively. The method was applied to the determination of
      TCs in pharmaceutical preparations and human urine with recoveries in the range
      95-105%.

PMID- 16416505
TI  - Recombinant polymer-protein fusion: a promising approach towards efficient and
      targeted gene delivery.
AB  - BACKGROUND: Synthetic vectors such as polymers have the potential to reduce the
      safety problems associated with viral vectors; however, their low transfection
      efficiency limits their clinical utility. To study the critical steps involved in
      an efficient transgene expression, there is a need for creative approaches that
      allow a systematic correlation between gene carrier structure and properties
      necessary for successful gene transfer. Using recombinant techniques a prototype
      vector comprised of tandem repeating units fused to a targeting moiety was
      biosynthesized to mediate gene transfer in mammalian cell lines. The carrier was
      designed to have the structure of (KHKHKHKHKK)6-FGF2 where lysine (K) residues
      would allow complexation with plasmid DNA, basic fibroblast growth factor (FGF2)
      to target cells over-expressing FGF2 receptors (FGFR), and histidine (H) residues
      to facilitate escape from the endosomal compartments. METHODS: The gene carrier
      was biosynthesized in E. coli, purified using a Ni-NTA column, characterized,
      complexed with pDNA, and the complexes were used to transfect NIH 3T3, T-47D and
      COS-1 mammalian cell types known to express FGFR. RESULTS: Results demonstrate
      the successful cloning and expression of the gene carrier with over 95% purity.
      The molecular weight of the gene carrier was determined by MALDI-TOF to be 27
      402. Amino acid content analysis and Western blot confirmed the expression of the
      gene carrier in E. coli. The vector was able to condense pDNA, induce cell
      proliferation in NIH 3T3 fibroblasts, and mediate transgene expression in NIH
      3T3, T-47D and COS-1 mammalian cell types. CONCLUSION: Genetic engineering
      techniques show promise for systematic investigation of structure-activity
      relationships of non-viral gene delivery vectors.

PMID- 16416506
TI  - Flow-injection chemiluminescence determination of catecholamines based on their
      enhancing effects on the luminol-potassium periodate system.
AB  - A rapid and sensitive chemiluminescence (CL) method using flow injection analysis
      is described for the determination of four catecholamines, dopamine, adrenaline,
      isoprenaline and noradrenaline, based on their greatly enhancing effects on the
      CL reaction of luminol-potassium periodate in basic solutions. The optimized
      chemical conditions for the chemiluminescence reaction were 1.0 x 10(-4) mol/L
      luminol and 1.0 x 10(-5) mol/L potassium periodate in 0.2 mol/L sodium hydroxide
      (NaOH). Under the optimized conditions, the calibration graphs relating the CL
      signal intensity (peak height) to the concentration of the analytes were
      curvilinear and they were suitable for determining dopamine, adrenaline,
      isoprenaline, and noradrenaline in the range 0.1-10 ng/mL, 0.1-100 ng/mL, 1-100
      ng/mL and 5-50 ng/mL, respectively, with the relative standard deviations of 0.8
      1.7%. The detection limits of the method are 0.02 ng/mL for dopamine, 0.01 ng/mL
      for adrenaline, 0.1 ng/mL for isoprenaline and 2.0 ng/mL for noradrenaline. The
      sampling frequency was calculated to be about 60/h. The selectivity of the method
      was good, because a series of common ions or excipients, such as K(+), Ba(2+),
      CO(3)(2-), NO(3)(-), SO(4)(2-), PO(4)(3-), sodium citrate, sodium bisulphite,
      oxidate dopamine, starch, lactose, carbamide and gelatin, could not produce
      interference when their concentrations were 1000-fold than those of dopamine. The
      present method was successfully applied to the determination of the four
      catecholamines in pharmaceutical injections.

PMID- 16416507
TI  - Generation of free radicals and electrochemiluminescence from simple aromatic
      molecules in aqueous solutions.
AB  - Oxide-covered aluminium electrodes were used to demonstrate that aromatic
      compounds, such as the simple derivatives of benzene, can be electrochemically
      excited at cathodically pulse-polarized conductor/insulator/electrolyte (C/I/E)
      tunnel junction electrodes (e.g. oxide-covered aluminium electrodes). The primary
      cathodic process at these electrodes was a tunnel emission of hot electrons into
      an aqueous electrolyte solution. Fluorescence (FL) and electrochemiluminescence
      (ECL) spectra were compared and the dependence of the electrochemiluminescence on
      the concentrations of benzene, toluene, phenol, p-cresol and aniline were
      measured and detailed mechanisms for the present electrochemiluminescence are
      proposed.

PMID- 16416508
TI  - Parent-teen disagreement of parent-imposed restrictions on teen driving after one
      month of licensure: is discordance related to risky teen driving?
AB  - The purpose of the investigation was to determine if parent-teen discordance for
      parent-imposed restrictions on driving conditions, driving rules, and the
      consequences for driving rule violations were related to risky teen driving. A
      total of 579 parents and their newly licensed teens were interviewed by
      telephone, 1 month after teens obtained provisional licenses. In multiple
      regression analyses, the degree of disagreement with parent restrictions on
      driving conditions and parent-imposed consequences for driving rule violations
      were negatively associated with a composite measure of teen risky driving. Female
      parents were negatively associated and male teens were positively associated with
      risky driving, but discordance with restricted driving conditions was the most
      important predictor. Discordance may reflect poor parent-teen relations or
      inadequate communication about parental expectations. The findings suggest that
      increasing parent-teen concordance on parent-imposed driving restrictions may
      help reduce risky teen driving.

PMID- 16416509
TI  - Re: Characteristics and relevance of clustering ventricular arrhythmias in
      defibrillator recipients.

PMID- 16416510
TI  - Tension-free vaginal tape (TVT) procedure.
AB  - OBJECTIVE: To provide an introduction to the tension-free vaginal tape(TVT)
      procedure, placing it in the context of minimally invasive surgeries for the
      treatment of urinary stress incontinence in women, and to provide guidance to
      surgeons counseling women on the merits of this surgical choice. OPTIONS: This
      discussion is limited to surgical treatment of urinary stress incontinence in
      women. EVIDENCE: A search of both MEDLINE and the Cochrane Library identified the
      most relevant medical evidence. This document represents an abstraction of the
      evidence rather than a methodological review. VALUES: This update is the
      consensus of the Sub-Committee on Urogynaecology of the Society of Obstetricians
      and Gynaecologists of Canada (SOGC). BENEFITS, HARMS, AND COSTS: Counseling for
      the surgical treatment of urinary incontinence should consider the harms-benefits
      ratios of various options and include a measure of the"weight" of the evidence.
      RECOMMENDATIONS: 1. The Burch procedure should be offered as the gold standard.
      The TVT procedure is promising but currently under evaluation in trials that will
      establish its efficacy and safety (II-3A). 2. Proper training is recommended
      prior to performing TVT procedures. 3. Long-term trial results are needed before
      the TVT procedure can be offered to patients as an equal alternative to the Burch
      procedure. VALIDATION: This technical update has been approved by the Sub
      Committee on Urogynaecology and Executive and Council of the SOGC.

PMID- 16416511
TI  - IX International Congress on Reproductive Immunology, 11-15 October 2004, Hakone,
      Japan.

PMID- 16416512
TI  - Recent publications in hematological oncology.

PMID- 16416513
TI  - Equal, but different? Ecological, individual and instrumental approaches to
      understanding determinants of health.

PMID- 16416514
TI  - Commentary: lay health workers in primary and community health care.

PMID- 16416515
TI  - Visualizing sense of community and social fragmentation.

PMID- 16416536
TI  - Images in Hematology. Gaucher cells and HIV.

PMID- 16416537
TI  - Focusing on this year's flu...use healthy handwashing...and when soap and water
      aren't handy, hand gels work well, too.

PMID- 16416538
TI  - When adults wear bike helmets, so do kids.

PMID- 16416539
TI  - Hyperactivity really IS common...and a new warning about treatment.

PMID- 16416540
TI  - Another approach to lice: fine-tooth comb.

PMID- 16416541
TI  - Recalls: Perrigo infant pain, cough/cold drops..."Bottle Sippers" pull-up bottle
      caps... Pottery Barn Kids Spindle Cribs...children's folding chairs...and Radio
      Flyer Classic Walker Wagon.

PMID- 16416542
TI  - Link found between over-the-counter pain relievers and hypertension.

PMID- 16416543
TI  - Unlocking the mysteries of memory. Recent studies focus on sensory memory
      restoration: audio, visual, and olfactory. The results could aid in the
      development of drugs to treat mental disorders.

PMID- 16416544
TI  - Frontotemporal dementia: faster progression than AD. Often characterized by
      bizarre behavioral changes, patients can also develop attendant ALS.

PMID- 16416545
TI  - Alcohol's double benefit: new brain cells, less dementia.

PMID- 16416546
TI  - New alcohol abuse drugs emerging. Anti-craving meds are finally here to treat
      alcohol dependence, recognized as a disease of the brain.

PMID- 16416547
TI  - Does what you eat cause IBS? Common foods, including chicken, eggs, milk and
      wheat, may be the culprits.

PMID- 16416548
TI  - Heart failure treatment guidelines often ignored. But medical centers with
      highest adherence had shorter lengths of stay and lower mortality rates.

PMID- 16416549
TI  - Beta-blockers enable safer non-cardiac surgery for high-risk patients.

PMID- 16416550
TI  - Exercise can relieve low back pain. The benefits of a physical therapy program
      are similar to those of spinal fusion surgery.

PMID- 16416552
TI  - Mammograms continue to be the front line of detection. Screening leads to better
      outcomes, beats other methods for detecting early or slow-growing tumors.

PMID- 16416551
TI  - Acupuncture helps ease knee osteoarthritis pain.

PMID- 16416554
TI  - Radiotherapy immediately after prostate surgery controls disease progression.

PMID- 16416553
TI  - Anastrozole called breast cancer "lifesaver". Recipients showed a 40 percent
      decrease in relapse risk when switched to anastrazole after tamoxifen.

PMID- 16416555
TI  - Will my nutrition improve quickly if I eat foods with a low glycemic index?

PMID- 16416556
TI  - [The impact of electromagnetic radiation at microwave frequency (9.8 HhZ)on the
      embryonic and postembryonic development of the tick Hyalomma asiaticum (Acarina,
      Ixodidae)].
AB  - Low-power (20 microW/cm2) microwave-modulated radiation at a carrier frequency of
      9.8 Hhz is shown to affect the course and specific features of ontogenesis of the
      ick H. asiaticum. The actin of microwave radiation on the development of H.
      asiaticum substantially depends on the frequency of microwave modulation of a
      signal and on the temperatures of an experiment. When the temperature is 22
      degrees C, there is a significant suppression of development of fed larvae and
      nymphs after exposure to microwave radiation at modulated signal frequencies of 3
      and 5 Hz/ The whole range of the tested modulation frequencies was 2 to 16 Hz.
      The hungry species of all developmental phases in H. asiaticum were virtually
      unresponsive to exposures. At 14 degrees C (a perithreshold temperature of H.
      asiaticum development), the action of microwave radiation changed from inhibitory
      to stimulating. At modulation frequencies of 3, 5 and 7 Hz, the proportion of
      hatching larvae was 42.5, 67.5 and 80.0%, respectively, and that of controls was
      2.5%. Whether the size of a H.asiaticum population can be controlled by a radar
      that provokes the development of ticks before winter by its radiation is
      discussed.

PMID- 16416557
TI  - False positive viral load results: recent problems and solutions.

PMID- 16416558
TI  - Johns Hopkins University  Center for Clinical Global Health Education is
      established.

PMID- 16416559
TI  - HIV update from the 43rd annual meeting of the Infectious Disease Society of
      America.

PMID- 16416561
TI  - Proceedings of the 2nd Alcala International Conference on Mathematical Ecology, 5
      9 September 2003, Madrid, Spain.

PMID- 16416560
TI  - Past Trends Assessment and Future Forecasts of Health Workforce, 21-23 April
      2005, Barcelona, Spain. Abstracts.

PMID- 16416562
TI  - [Proceedings of the National Conference: Environmental and occupational exposure
      to inorganic lead: assessment of toxic effects of current doses and related
      preventive measures. Brescia, Italy, 28-29 June 2004].

PMID- 16416563
TI  - Institute for the Study of Aging (ISOA) 5th annual investigators meeting: Recent
      Advances in Drug Discovery and Development for Alzheimer's Disease.

PMID- 16416565
TI  - Abstracts of the XXIII Annual Scientific Meeting of the British Blood Transfusion
      Society, Telford, UK, 1-4 December 2005.

PMID- 16416564
TI  - [Treatment of ST-elevation acute coronary syndrome with the aim of reperfusion].

PMID- 16416566
TI  - Abstracts of the 2005 Australian Conference of Science and Medicine in Sport, 5th
      National Physical Activity Conference, 4th National Sports Injury Prevention
      Conference. Melbourne, Australia, 13-16 October 2005.

PMID- 16416567
TI  - Clinical laboratory reference 2005-2006.

PMID- 16416568
TI  - VEITHsymposium 2005. Abstracts.

PMID- 16416569
TI  - [90-year-old male with a hyperkeratotic lichenoid skin eruption].

PMID- 16416570
TI  - ISOBM 2005. Abstracts of the XXXIII Meeting of the International Society for
      Oncodevelopmental Biology and Medicine, Rhodes, Greece, September 24-28, 2005.

PMID- 16416571
TI  - [Cryotherapy in dermatology].

PMID- 16416572
TI  - Abstracts of the 4th Croatian Congress of Nephrology, Dialysis and
      Transplantation, Rovinj, Croatia, 7-10 October 2005.

PMID- 16416573
TI  - [Re: Restless legs syndrome and periodic limb movements during sleep in a patient
      with obstructive sleep apnea].

PMID- 16416574
TI  - Abstracts of the 5th IASSCS Conference: Sexual Rights and Moral Panics. San
      Francisco, California, USA, June 21-24, 2005.

PMID- 16416575
TI  - [130th anniversary of the birth of Dr. Otakar Srdinko].

PMID- 16416576
TI  - Abstracts of the 14th Annual Meeting of the Israel Society for Neuroscience and
      the Joint Germany-Israel Meeting on the Neural Basis of Behavior, Eilat, Israel,
      December 11-14, 2005.

PMID- 16416578
TI  - [Abstracts of the 2nd German Congress for Perinatal Medicine, Berlin, Germany, 1
      3 December 2005].

PMID- 16416577
TI  - Cardiac Surgery in the 3rd Millennium--Biological Solutions. Abstracts of the 1st
      International Congress,, November 30-December 2, 2005, Salzburg, Austria.

PMID- 16416579
TI  - [Author and subject index. Czech and Slovak Ophthalmology volumes 5-10 (1995
      2004)].

PMID- 16416580
TI  - Quality patient care is a team effort.

PMID- 16416581
TI  - What coaching methods work best with employees?

PMID- 16416583
TI  - Month-end numbers.

PMID- 16416582
TI  - Less is more. Why physicians should take their own vitals.

PMID- 16416584
TI  - Power to the consumers. General session speakers describe assertive shopping for
      health care.

PMID- 16416585
TI  - Medicare drug program just around the corner. What your practice needs to know.

PMID- 16416586
TI  - Why nonphysician providers?

PMID- 16416587
TI  - CMS delays full release of much-publicized VistA-office EHR.

PMID- 16416588
TI  - Turn, turn, turn. An introduction to the revenue cycle.

PMID- 16416589
TI  - Out of their pockets. 10 ways to improve collections from self-pay patients.

PMID- 16416590
TI  - Medical management and business ethics. Building a culture of trust.

PMID- 16416591
TI  - Stepping stones. Assess, learn, certify and excel on your pathway to professional
      development.
AB  - Here's a guided tour of the process of pursuing professional development in
      medical practice management--and achieving measurable success. Peers describe
      what they did to broaden their knowledge and work toward certification in the
      field. They describe the many resources available to members of the Medical Group
      Management Association and its certification body, the American College of
      Medical Practice Executives.

PMID- 16416593
TI  - Fraud and abuse enforcement trends. What's hot for physicians and physician
      practices.
AB  - The Department of Health and Human Services Office of Inspector General (OIG) has
      dramatically expanded the scope and frequency of physician fraud and abuse
      investigations. Further, OIG has increasingly extracted financial settlements and
      obtained sanctions against physicians. This article identifies seven areas of
      investigation that will be given highest priority.

PMID- 16416592
TI  - 'Tablet' makes for good medicine. Case study: tablet-style computers can enhance
      physician satisfaction, revenue stream.
AB  - Shawnee Mission (Kan.) Medical Center's affiliated medical practice, Shawnee
      Mission Physicians Group, is developing an inexpensive, cost-effective solution
      for electronic patient charge capture. It helps physicians track their inpatient
      services and billable encounters, integrates with their medical practice
      information technology scheduling and billing systems, and can incorporate
      forthcoming hospital-based digital radiology viewing and an electronic medical
      record. Learn how the system works and how the technology benefits the two
      organizations.

PMID- 16416594
TI  - Map quest.

PMID- 16416595
TI  - Characterization of polyclonal antibodies raised against a linear peptide
      determinant of desmoglein-3.
AB  - Our labs are pursueing the goal of exactly defining the qualities of peptide
      antigenicity, immunogenicity and pathogenicity in order to develop safe specific
      immunotherapies by utilizing specific portions of disease-associated-proteins
      (DAPs). Using as a model the Pemphigus vulgaris antigen (PVA) desmoglein 3
      (Dsg3), we have studied the murine humoral response against the Dsg3 amino acid
      49-60 peptide sequence, previously characterized as sequence having low
      similarity to the mouse proteome. The results show that the low-similarity
      Dsg3(49-60)REWVKFAKPCRE peptide does not elicit pathogenic antibodies.

PMID- 16416596
TI  - Correlation between crystal violet dissolution assay and manual colony counting
      on the in vitro effects of Hsp90-inhibitors.
AB  - Radiobiological experiments routinely require the estimation of cellular
      survival. Several cytotoxicity assays have been proposed, which have inherent
      advantages and disadvantages. The performance of one of them, the crystal violet
      dissolution assay, was examined under a broad range of conditions. PC-3M prostate
      carcinoma cells were exposed to ionizing radiation in the presence or absence of
      heat shock protein 90-inhibiting drugs. Colony formation as assessed by
      traditional manual counting was compared with the results from the crystal violet
      dissolution assay. The overall bivariate correlation of the data was determined
      (r = 0.743, p < 0.01). The variabilities of the data distributions from two
      different observers were quantitated and found to agree fairly. Ionizing
      radiation has a scattering-reducing effect that if plotted as Pearson-coeffcient
      versus radiation energy dose yields a sigmoidal distribution of data points. The
      crystal violet dissolution assay is a convenient tool for the rapid and
      reproducible determination of cellular survival and under appropriate conditions
      exerts a reasonable correlation to colony number.

PMID- 16416597
TI  - Antitumor activity of Nitronaphthal-NU, a novel mixed-function agent.
AB  - Nitronaphthal-NU (Compound 1) was synthesized as a mixed-function antitumor agent
      based on the structures of the clinical drug CCNU and experimental compound
      Mitonafide. In vitro screening in four human tumor cell lines namely SNB-78 CNS,
      HOP-62 Lung, T47D Breast and SiHa - cervix revealed significant cytotoxicity in
      the former two cell lines much greater than CCNU and comparable to Mitonafide
      used as standards. In vivo antitumoral potency assessed in the murine ascites
      tumors Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the
      increase in median survival times of drug treated (T) over untreated control (C)
      mice, revealed highly significant (p<0.001) tumor regression effects greater than
      standards. Life span of mice bearing advanced tumor for 10 days before the drug
      challenge was also considerably increased. Its toxicity was assessed in vivo in
      normal and S-180 bearing mice by measuring drug-induced changes in haematological
      parameters, femoral bone marrow and splenic cellularities as well as
      hepatotoxicity and nephrotoxicity sequentially on days 9, 15 and 21 following
      drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. Results indicate
      that it did not adversely affect haematopoiesis. The other parameters were within
      normal limit. The compound comparable to standards inhibited the synthesis of DNA
      and RNA in S-1 80 tumor cells.

PMID- 16416598
TI  - Actin content and actin polymerization in hepatoma Morris 5123 tumor bearing rats
      after treatment with cysteine protease inhibitor and vitamin E.
AB  - AIM: Actin microfilaments are components of cytoskeleton, the structure involved
      in many cellular functions, including cell motility, and morphology, its
      necessary for tumor progression and metastasis. We investigated the effects of
      vitamin E and human placetal cysteine protease inhibitor (CPI) on actin content
      and polymerization after implantation the hepatoma Morris 5123 tumor in Buffalo
      rat. METHODS: We measured the size and survival animals treated with human
      placental cysteine protease inhibitor (CPI) plus vitamin E and none treated rats.
      Also measured the actin content and polymerization in the tumor and liver tissues
      by the inhibition of DNase I from bovine pancreas under standard assay conditions
      RESULTS: We observed that the combination 10 mg of vitamin E plus 200 microg CPI
      obtained the best results than authors. In those cases the animals survived for
      longer than 4 weeks. In numerous cases the 70 % of tumors disappeared following
      CPI and vitamin E application. The number of complete tumor responses was higher
      after combination 10 mg of vitamin E plus CPI 200 microg i.e. 5/7 rats than
      others group. We showed statistically significant decrease of monomeric (G),
      filamentous (F) and total actin as well as the F:G ratio level in tumor tissues
      after the rats was treated with CPI plus vitamin E in comparison with control
      animals. CONCLUSIONS: The new therapy may be the way for therapeutic
      intervention, aimed at stopping and possibly reversing the process of metastatic
      growth, with the use of drugs affecting actin polymerization.

PMID- 16416599
TI  - Differential proteomic serum pattern of low molecular weight proteins expressed
      by adenocarcinoma lung cancer patients.
AB  - Based on the assumption that proteins can emanate from tumour to serum, we
      investigated whether serum low molecular weight proteins (LMW) can discriminate
      lung cancer patients from healthy donors. Pooled sera from 20 lung cancer
      patients matched in sex (men), histological type (adenocarcinoma) and stage (IIIB
      and IV) and from 20 healthy donors (men) were submitted to 2-DE coupled to MALDI
      TOF peptide mass fingerprinting. Results of 2D-E/ MALDI-TOF showed five up
      regulated proteins (immunoglobulin lambda chain, transthyretin monomer,
      haptoglobin-alfa 2 and two isoforms of serum amyloid protein) and one down
      regulated (fragment of apolipoprotein A-I) in patients. All differentially
      expressed proteins, except immunoglobulin, may be acting as a non-specific sign
      of inflammation in cancer and transthyretin monomer may act as a possible blood
      marker to CSF barrier disruption that occurs, e.g., in cerebral metastasis. In
      conclusion, this work shows the usefulness of 2D-gel electrophoresis and mass
      spectrometry proteomic techniques for the identification of up- and down
      regulated proteins in serum from adenocarcinoma lung cancer patients.

PMID- 16416600
TI  - Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated
      apoptosis through activation of procaspases and release of cytochrome c from
      mitochondria.
AB  - Malignant glioma cells are generally resistant or only weakly sensitive to tumor
      necrosis factor family of cell death-inducing ligands, including TNF-related
      apoptosis-inducing ligand (TRAIL)/Apo2L. The chemopreventive activity of
      polyphenolic compounds present in plant-derived food products has been well
      recognized in epidemiological studies; however, the mechanism of chemoprevention
      by these dietary constituents largely remains unknown. Curcumin, the yellow
      pigment in the spice turmeric, has profound anti-inflammatory activity and
      exhibits chemopreventive and tumor growth inhibitory activity. In the present
      study, we investigated whether curcumin sensitizes malignant glioma cell lines
      U251MG and U87MG to TRAIL-induced apoptosis. Treatment with low concentrations (5
      20 microM) of curcumin alone had no effect on the viability of either cell line.
      At low concentration (5 ng/ml) TRAIL induced cytotoxicity in U251MG cells but not
      in U87MG cells. Whereas curcumin at subtoxic concentration sensitized U87MG cells
      to TRAIL-induced cytotoxicity, it had no effect on TRAIL-mediated cytotoxicity in
      U251MG cells. The combined curcumin and TRAIL treatment enhanced accumulation of
      hypo-diploid U87MG cells in sub G1 cell cycle phase and induced the cleavage of
      procaspases-3, -8, -9 and release of cytochrome c from mitochondria. These data
      indicate that curcumin differentially sensitizes glioma cells to TRAIL-induced
      apoptosis through the activation of both extrinsic (receptor-mediated) and
      intrinsic (chemical-induced) pathways of apoptosis. These results define a
      potential use of curcumin to sensitize glioma cells for TRAIL-mediated
      immunotherapy.

PMID- 16416601
TI  - Expression of cystatin C in clinical human colorectal cancer tissues.
AB  - We studied the relation between the antipapain activity of cysteine proteinase
      inhibitors (CPI) and immunohistochemical staining for cystatin C, using anti
      chicken cystatin antibodies, in the colorectal cancer tissues. In primary tumour
      tissues immuno-peroxidase reactivity was present in the cytoplasm and on the cell
      surface membranes. Sections of non malignant tissues showed no staining. The
      percentages of positive staining were greater for adenocarcinoma than
      carcinoma,100% and 77% respectively. Antipapain activity which was increased in
      malignant tissues in comparison to control, rose successively from well
      differentiated carcinomas through moderately to poor differentiated. Invasive
      adenocarcinomas had higher antipapain activity than noninvasive ones. The results
      indicated that immunohistochemical detection of cystatin using anti-chicken
      cystatin antibodies could be useful in studying the prognostic significance of
      cystatin C expression in colorectal cancer.

PMID- 16416602
TI  - Evaluation of targeted arterial delivery of the branched chain fatty acid 12
      methyltetradecanoic acid as a novel therapy for solid tumors.
AB  - The purpose of this research was to evaluate the effects of targeted arterial
      delivery of the branched chain fatty acid 12-methyltetradecanoic acid (12-MTA) on
      the VX2 squamous cell carcinoma in rabbits. An intramuscular VX2 squamous cell
      carcinoma was induced at a single site in the right thigh of 39 New Zealand white
      rabbits. Approximately 10 days after inoculation, a 3-French catheter was
      introduced into the right common carotid artery and positioned using fluoroscopic
      guidance in the right deep femoral artery, which was the main, if not exclusive,
      artery supplying the tumor. Ethiodol alone (targeting agent), Ethiodol containing
      12-MTA, or Ethiodol containing myristic acid was then injected through the
      catheter. Tumor growth and histopathology were evaluated 7-8 days after
      treatment. Caspase-3 activity was evaluated 2 days after therapy, and tumor
      tissues were assayed for eicosanoid metabolites 2 and 7 days after treatment to
      assess the effects of the branched chain fatty acid on the lipoxygenase (LOX) and
      cyclooxygenase-2 (COX-2) enzyme systems. Targeted arterial delivery of 12-MTA
      resulted in dose-dependent growth inhibition of intramuscular rabbit VX2 tumors
      while myristic acid, a saturated fatty acid of the same carbon length as 12-MTA,
      was found to stimulate tumor growth. Two and 7 days following treatment, tumors
      treated with 12-MTA showed a significant decrease in 5-hydroxyeicosatetraenoic
      acid (5-HETE) and a concomitant increase in 15-HETE levels while tumors treated
      with myristic acid exhibited a significant increase in prostaglandin E2 (PGE2)
      levels. Western blot as well as immunohistochemical analysis showed that 5-LOX
      and COX-2 proteins were present in the VX2 tumors. No alterations in tumor/tumor
      cell morphology or caspase-3 activity were evident on microscopic examination
      following treatment. These studies suggest that targeted arterial delivery of
      branched chain fatty acids such as 12-MTA may be considered as a potential new
      therapy for treatment of solid tumors. The exact mechanism(s) responsible for the
      observed inhibition of VX2 tumor growth by 12-MTA is unclear. Additional in vivo
      studies are warranted to elucidate 12-MTA's mechanism of action and further
      investigate the branched chain fatty acid's antitumor effects.

PMID- 16416604
TI  - Evaluation of the American Joint Committee on Cancer staging system for cutaneous
      squamous cell carcinoma and proposal of a new staging system.
AB  - PURPOSE: To identify and propose corrections for deficiencies in the American
      Joint Committee on Cancer (AJCC) system for staging cutaneous squamous cell
      carcinoma (CSCC). MATERIALS AND METHODS: Prognostic factors for CSCC were
      identified by retrospective analysis of the published literature. Limitations and
      deficiencies in the current AJCC staging system for CSCC were then determined
      using these prognostic factors. RESULTS: Size, histologic differentiation,
      location, previous treatment, depth of invasion, tumor thickness, histologic
      subtype, perineural spread, and scar etiology are the most powerful tumor
      prognostic indicators in patients with localized disease. The most important
      prognostic factors for patients with nodal metastases are the location, number,
      and size of the positive lymph nodes. Proposed changes for the T classification
      include increased stratification of tumor size, identification of patients with
      perineural invasion, and the addition of tumor thickness or depth of invasion.
      The N classification has been expanded to include the number and size of nodal
      metastases. CONCLUSION: The current AJCC staging system for carcinoma of the skin
      has deficiencies that limit its use for CSCC. The proposed TMN staging system for
      CSCC more accurately reflects the prognosis and natural history of CSCC.

PMID- 16416603
TI  - EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human
      colon cancer cells.
AB  - Increased expression of COX-2 appears to play an important role in the
      development of colorectal cancer. The level of COX-2 expression is regulated by
      various factors including activation of members of the EGFR family of RTKs. We
      previously reported that in HT29 human colon cancer cells EGCG, the major
      biologically active component of green tea, inhibits activation of two members of
      this family, EGFR and HER2, and multiple downstream signaling pathways. In this
      study we examined the effects of EGCG on the HER3 RTK and on COX-2 expression in
      the SW837 human colon cancer cell line that expresses a high level and
      constitutive activation of HER3 and also expresses a high level of COX-2.
      Treatment of these cells with 20 microg/ml of EGCG (the IC50 concentration for
      growth inhibition) caused, within 6 hours, a decrease in the phosphorylated (i.e.
      activated) forms of not only EGFR and HER2, but also HER3. At 6 to 12 hours there
      was a decrease in the phosphorylated forms of the downstream signaling proteins
      ERK and Akt. Within 6 to 12 hours there was a decrease in cellular levels of both
      COX-2 protein and mRNA, and within 48 hours the cells displayed apoptosis.
      Reporter assays indicated that EGCG inhibited the transcriptional activities of
      the COX-2, AP-1, and NF-kappaB promoters. EGCG also caused a decrease in
      production of PGE2, a major product of COX-2. With a longer incubation time, 96
      hours, a very low dose (1.0 microg/ml) of EGCG also caused inhibition of cell
      growth, inhibition of activation of EGFR, HER2, and HER3, a decrease in the
      levels of COX-2 and Bcl-xL proteins, and apoptosis. These results provide the
      first evidence that a low concentration of EGCG can inhibit activation of, at
      least, three members of the EGFR family of RTKs, and also inhibit COX-2
      expression in colon cancer cells. These findings extend our previous evidence
      that EGCG may be useful in the chemoprevention and/or treatment of colorectal
      cancer.

PMID- 16416605
TI  - Single-institution experience in the management of patients with clinical stage I
      and II cutaneous melanoma: results of sentinel lymph node biopsy in 240 cases.
AB  - BACKGROUND: Lymphatic mapping and sentinel lymph node biopsy (SLNB) has been
      developed as a minimally invasive technique to determine the pathologic status of
      regional lymph nodes in patients without clinically palpable disease and
      incorporated in the latest version of the American Joint Committee on Cancer
      (AJCC) staging system for cutaneous melanoma. OBJECTIVE: To analyze the results
      of SLNB and the prognostic value of the micrometastases and the pattern of early
      recurrences in patients according to sentinel lymph node (SLN) status. METHOD:
      Patients with cutaneous melanoma in stages I and II (AJCC 2002) who underwent
      lymphatic mapping and SLNB from 1997 to 2003 were included in a prospective
      database for analysis. RESULTS: The rate of identification of the SLN was 100%.
      Micrometastases to SLN were found in 20.8% of patients. The rate of SLN
      micrometastases increased according to Breslow thickness and clinical stage.
      Breslow thickness of 0.99 mm was the optimal cutpoint for predicting the SLNB
      result. Twenty-four patients (12.3%) developed a locoregional or distant
      recurrence at a median follow-up of 31 months. Recurrences were more frequent in
      patients with a positive SLN. Among patients who had a recurrence, those with a
      positive SLN were more likely to have distant metastases than those with negative
      SLN. Nodal recurrences were more frequent in patients with a negative SLN
      compared with those with a positive SLN. CONCLUSIONS: The status of the SLN
      provides accurate staging for identifying patients who may benefit from further
      therapy and is the most important prognostic factor of relapse-free survival.

PMID- 16416606
TI  - Postsurgical use of imiquimod 5% cream in the prevention of earlobe keloid
      recurrences: results of an open-label, pilot study.
AB  - BACKGROUND: Traditional surgical modalities for the management of earlobe keloids
      are often associated with high recurrence rates. A recent report suggests that
      imiquimod 5% cream can be effective in the prevention of keloid recurrences after
      surgical excision. OBJECTIVES: To establish the safety and efficacy of imiquimod
      5% cream in the prevention of recurrences of excised earlobe keloids. METHODS:
      Patients who attended a dermatologic surgery clinic for the treatment of earlobe
      keloids were recruited into the study. Earlobe keloids underwent parallel shave
      excision. Imiquimod 5% cream was applied daily for 8 weeks followed by an
      observation period of 16 weeks. In patients who presented with bilateral earlobe
      keloids, paired comparisons of imiquimod versus intralesional steroid injections
      were performed. RESULTS: Eight earlobes were treated with imiquimod 5% cream
      after parallel keloid removal. Twenty-four weeks after surgery, six (75%)
      remained recurrence free. Four patients underwent bilateral paired comparisons.
      At the end of the observation period, two patients (50%) remained recurrence free
      in the imiquimod-treated areas while experiencing recurrences in the
      intralesional steroid-treated areas. Local irritation secondary to imiquimod
      application required rest periods in three cases. In all cases, patients were
      able to resume therapy and completed the study without further complications.
      CONCLUSION: Although small and uncontrolled, the results of this open-label,
      pilot study suggest that imiquimod 5% cream may prove to be a reasonably
      effective adjuvant therapeutic alternative for the prevention of recurrences in
      excised earlobe keloids.

PMID- 16416607
TI  - Double-blind, randomized, placebo-controlled, prospective study evaluating the
      tolerability and effectiveness of imiquimod applied to postsurgical excisions on
      scar cosmesis.
AB  - BACKGROUND: It has been reported that topical application of imiquimod 5% cream
      induces interferon-alpha, an antifibrotic cytokine. OBJECTIVE: To determine the
      tolerability and effectiveness on the cosmetic outcome of the application of
      imiquimod to postsurgical excision sites. MATERIALS AND METHODS: A prospective,
      double-blinded, randomized, vehicle-controlled trial was conducted among 20
      patients with two skin lesions clinically diagnosed as melanocytic nevi.
      Imiquimod 5% cream was applied to one of the sutured surgical wounds starting the
      night of the excision nightly for a period of 4 weeks. The second sutured
      excision site was treated with vehicle cream. Scar cosmesis, erythema, pigmentary
      alterations, induration, tenderness, and pain were assessed using a visual
      analogue scale 2, 4, and 8 weeks after surgery. RESULTS: Eighteen subjects
      completed the study, with a total of 36 excision sites; no wound site dehisced,
      and no signs of infection were noted. Surgical wounds treated with imiquimod had
      more erythema, pigmentary alterations, and lower cosmesis rated by the
      investigator compared with wounds treated with placebo, both becoming
      nonsignificant in further evaluations. For pigmentary alterations, induration,
      and cosmesis rated by the patients, no statistically significant difference
      between treatment groups was observed at week 8. CONCLUSION: Treatment of
      surgical excision-site wounds with imiquimod was well tolerated and without
      serious adverse events. Evaluations for cosmesis of placebo-treated surgical
      sites were better than imiquimod-treated sites at week 8, becoming nonsignificant
      later.

PMID- 16416608
TI  - Induction of vascular endothelial growth factor messenger ribonucleic acid
      expression in stored micrografts by aminoguanidine.
AB  - BACKGROUND AND OBJECTIVES: Aminoguanidine (AMG) has been found to inhibit
      apoptotic cell death in hair follicle micrografts and improves the viability of
      isolated micrografts during the storage period in hair restoration surgery. In
      this study, we investigated the effect of AMG on messenger ribonucleic acid
      (mRNA) synthesis of growth factors in stored micrografts and primary cultures of
      follicle-derived cell populations. METHOD: Hair follicles were obtained from 10
      different patients undergoing routine micrograft transplant and were stored for 5
      hours at room temperature in phosphate-buffered saline containing different
      concentrations of AMG. After a culture period of 72 hours, quantitative changes
      of mRNA for basic fibroblast growth factor (bFGF), insulin-like growth factor 1
      (IGF-1), and vascular endothelial growth factor (VEGF) were determined by real
      time reverse transcriptase-polymerase chain reaction (RT-PCR). Primary cell
      cultures of dermal papilla and outer root sheath cells were stimulated for 72
      hours with AMG followed by RT-PCR measurement of growth factor mRNA. RESULTS: A
      dose-dependent induction of VEGF mRNA could be demonstrated in stored micrografts
      after stimulation with AMG (unstimulated: 1.0 [0.7-2.2]; AMG 10 pg/mL: 5.6 [3.1
      9.7], p < .05; AMG 50 pg/mL: 6.9 [5.7-10.0], p < .05; AMG 100 microg/mL: 17.1
      [14.1-22.3], p < .001). Expression of bFGF mRNA and IGF-1 mRNA levels was not
      influenced by AMG stimulation. Stimulation of cultured dermal papilla and outer
      root sheath cells demonstrated 14-fold induction of VEGF mRNA by AMG in outer
      root sheath cells (unstimulated: 1.0 [0.8-1.4]; AMG 100 pg/mL: 14.0 [12.5-16.1],
      p < .01), and no changes in VEGF mRNA levels were detected in dermal papilla
      cells. CONCLUSIONS: Our study demonstrated induction of VEGF mRNA in stored
      micrografts by AMG. Although the clinical relevance in post-transplant hair
      growth and wound healing needs further evaluation, the possibility of actively
      influencing growth factor production in isolated micrografts during the storage
      period is the basis for the development of hair follicle growth-promoting storage
      solutions in the future.

PMID- 16416609
TI  - The undesirable influence of reconstructive procedures on the symmetry of the
      nasolabial folds.
AB  - BACKGROUND AND OBJECTIVES: Although considerable attention has been directed
      toward the nasolabial fold in the esthetic surgery literature, there are
      infrequent discussions of the fold's importance in reconstructive surgery of the
      face. Because the use of common reconstructive techniques for wounds of the
      central face often introduces undesirable asymmetry to the nasolabial folds,
      reconstructive surgeons should be more aware of the esthetic consequences of
      manipulating the nasolabial folds. METHODS: The influence of selected
      reconstructive procedures of the central face on the form and symmetry of the
      nasolabial folds is analyzed through the examination of multiple clinical
      examples of reconstructive successes and failures in this area. RESULTS: Many
      commonly performed reconstructive procedures of the face introduce changes in the
      nasolabial fold's depth, slope, and location. The inherent asymmetries that such
      procedures introduce frequently detract from their overall esthetic results.
      CONCLUSIONS: The nasolabial fold is a visually distinct unit of the face that
      deserves more attention from reconstructive surgeons. When possible, surgical
      alterations of the fold should be minimized to preserve facial symmetry.

PMID- 16416610
TI  - Role of multiple scouting biopsies before Mohs micrographic surgery for
      extramammary Paget's disease.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) frequently extends subclinically,
      resulting in high recurrence rates after surgical excision. Mohs micrographic
      surgery (MMS) improves cure rates but may require time-consuming reexcision of
      subclinical extension. A mechanism to estimate the location and extent of
      subclinical extension would be helpful. OBJECTIVE: To describe and evaluate a
      technique for multiple scouting biopsies before MMS for EMPD. METHOD: A
      retrospective review of patients at Mayo Clinic who had multiple scouting
      biopsies before MMS for EMPD without dermal invasion. TECHNIQUE: The clinical
      extent of EMPD is identified. The scouting biopsy sites are determined and
      documented with photographs. The scouting biopsy specimens are sent for permanent
      sections. The results of the scouting biopsies help guide the extent of the
      initial Mohs layer. The tumor is cleared with MMS. An additional 1 mm peripheral
      margin of tissue is usually submitted for permanent sections. RESULTS: Multiple
      scouting biopsies were done in five patients. Four of the five patients had at
      least one true-positive result. At least one true-negative result was obtained in
      all five patients. Two patients had at least one false-negative result.
      CONCLUSION: Multiple scouting biopsies before MMS for EMPD without dermal
      invasion can be a beneficial adjuvant technique.

PMID- 16416611
TI  - Squamous cell carcinoma of the auricle and Mohs micrographic surgery.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) of the ear compared with SCC occurring
      at other skin sites has an increased incidence of recurrence following treatment.
      OBJECTIVE: To determine the following variables: patient age and gender, life
      status, tumor location, and recurrence rate following Mohs micrographic surgery
      (MMS). METHODS: The charts of 117 patients with 144 invasive SCCs of the auricle
      were reviewed. The patients were contacted by telephone to confirm tumor
      recurrence and patients' life status. The range of follow-up was 7 to 67 months
      (average 34.6 months) after MMS. RESULTS: The patients' ages ranged from 34 to 90
      years (mean age 71 years). The male to female ratio was 22:1. The helix was the
      most common site of occurrence (50.7%). Local recurrence after MMS was found in
      four patients (five tumors). MMS was performed on these five recurrent tumors,
      with no further recurrences. Telephone confirmation was obtained on 91 patients
      (26 patients could not be contacted) with 122 tumors, which included the 4
      patients with 5 recurrent tumors. There were no additional recurrences. Of these
      122 tumors, 35 were followed for less than 2 years (average 16.6 months), and 87
      were followed for 2 years or more (average 41.8 months). From the chart review
      and telephone contact, the 2-year local recurrence rate was 5.7% (5 of 87 tumors)
      after MMS. The average size of these 87 tumors was 3.5 cm2. Twelve of 91 patients
      had died with evidence of active disease from causes unrelated to SCC.
      CONCLUSION: Invasive SCC of the ear was once a formidable disease with a severe
      prognosis. The course of this disease has been appreciably improved by early
      diagnosis and treatment with MMS.

PMID- 16416612
TI  - Management of scalp dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans is a relatively rare, locally
      aggressive soft tissue tumor. Less than 5% of these tumors are located on the
      scalp; however, the recurrence rates for this region are high compared with those
      of more common locations, such as the trunk and proximal extremities. Standards
      for the management of dermatofibrosarcoma protuberans in general have been
      established in the literature, including wide local excision and Mohs
      micrographic surgery. OBJECTIVE: To describe optimum treatment options for
      primary and recurrent dermatofibrosarcoma protuberans of the scalp based on cases
      from Roswell Park Cancer Institute (RPCI) and from the literature. METHODS: Five
      cases from RPCI and 23 cases from the literature were reviewed. Age, sex,
      history, tumor size and level of invasion, treatment, reconstruction method, and
      follow-up were compiled from each case. RESULTS: Twenty-eight cases of scalp
      dermatofibrosarcoma protuberans were found; 13 were primary, 8 were recurrent,
      and 3 had persistent positive margins. Fifty-eight percent had classic histologic
      findings; seven tumors invaded beyond the periosteum. Twenty tumors were treated
      by surgical excision, whereas eight tumors were treated with Mohs micrographic
      surgery, requiring between two and four layers. Advanced surgical reconstruction
      was used in most cases to close the defects. Four patients experienced one tumor
      recurrence, whereas three other patients had several local recurrences. One
      patient died of his disease, and one died during surgical treatment of
      dermatofibrosarcoma protuberans. CONCLUSIONS: Mohs micrographic surgery or a
      modified version may be the best treatment option for scalp dermatofibrosarcoma
      protuberans to ensure complete removal of tumor and minimize recurrence. Surgeons
      should be prepared for advanced reconstruction following tumor removal.

PMID- 16416613
TI  - Are patients better than the laboratory in assessing sweating? Validation study.
AB  - BACKGROUND: Primary focal hyperhidrosis is a hereditary condition characterized
      by excessive sweating affecting a variety of areas, including the palms. In most
      cases, the decision to treat a patient is based only on the patient's own
      description of the symptoms because laboratory tests have not been established in
      clinical practice. OBJECTIVE: To validate a subjective self-assessment scale for
      sweating in comparison with an objective method of quantifying evaporation from
      the skin surface. METHODS: We studied palmar sweating in 20 patients with primary
      focal hyperhidrosis and 20 age- and gender-matched controls. Four times in each
      subject, we obtained measurements of the evaporation in palms and the self
      evaluation scale (SES) scores on a proportional scale from 0 (no sweating) to 10
      (worst imaginable sweating). RESULTS: Good correlation was found between the SES
      score and evaporation assessment (R = .65). The SES score was easier to obtain
      and provided better diagnostic sensitivity and specificity. They leveled out at
      over 80% when a score of 3 was used as the threshold level; for evaporimetry,
      sensitivity equalled specificity at 70% at the threshold 90 mg -2h(-1).
      CONCLUSION: We confirm the usefulness of the SES in assessing palmar sweating and
      discuss the current restrictions in its use in clinical diagnosis. We propose
      that the scale can be added effortlessly to research or clinical protocols to
      provide the necessary validation in wider spectra of patients.

PMID- 16416614
TI  - Cotton-tipped applicators used in surgery of the nose.
AB  - BACKGROUND: A variety of uses have been described for cotton-tipped applicators.
      OBJECTIVE: We describe an additional application in surgeries involving the nose.
      This technique uses 8-inch obstetrics-gynecology applicators with oversized
      cotton tips, unlike most articles, which report the use of 6-inch applicators
      with smaller cotton heads. The applicators function to stabilize and support the
      nasal structures and thus provide a steadier operating field. CONCLUSION: It can
      be used in procedures of the nose, including curettage, electrocautery,
      hemostasis, and Mohs and other surgical excisions.

PMID- 16416615
TI  - Use of a deep polypropylene suture during earlobe repair: a method to provide
      permanent reinforcement in the prevention of recurrent earlobe tract elongation.
AB  - BACKGROUND: Cosmetic repair of elongated or lacerated earlobe tracts is a
      commonly encountered dermatologic procedure. For esthetic purposes, patients may
      choose to repierce the repaired lobe over the original site. Subsequent piercing
      within a scarred area potentially increases the risk of recurrent tract
      elongation secondary to the reduced tensile strength of the scar. OBJECTIVE: To
      strengthen a damaged earlobe by incorporating a nonabsorbable, dermal
      polypropylene suture during earlobe METHODS: The technique is described within
      the text. RESULTS: A deep polypropylene suture placed within a repaired earlobe
      tract provides a permanent barrier above which repiercing can be performed.
      CONCLUSION: Permanent reinforcement of the repaired earlobe serves to reduce the
      possibility of recurrent elongation of the earlobe tract. The technique is
      relevant when repeat piercing is desired over the original site.

PMID- 16416616
TI  - Hereditary inheritance of nevus sebaceus.

PMID- 16416617
TI  - Perialar crescentic advancement flap for upper cutaneous lip defects.

PMID- 16416618
TI  - Dermoscopic evolution of a congenital combined nevus in childhood.
AB  - BACKGROUND: A combined nevus most commonly consists of a blue nevus in
      combination with a Clark or Spitz nevus. Dermoscopically, combined nevus can
      mimic melanoma owing to the presence of dermoscopic features common to both types
      of lesions. Benign clinical and dermoscopic changes can occur in nevi over time,
      especially in children and young adults. OBJECTIVE: To describe the dermoscopic
      evolution of a congenital combined nevus showing unusual dermoscopic features.
      METHODS: Digital dermoscopic analysis was performed at the initial visit and
      after 8 months. The lesion was surgically excised and histopathologically
      examined. RESULTS: An asymptomatic plaque with a central blue area and peripheral
      brown pigmentation located on the back of a 13-year-old boy was diagnosed
      dermoscopically as combined nevus. Dermoscopic analysis 8 months later showed
      color changes from steel blue to gray-blue and black in the central area of the
      lesion, an increased number of blue-black dots or globules, and peripheral
      irregular streaks. Histopathology revealed typical features of a congenital
      combined nevus (blue nevus + compound nevus). CONCLUSION: Over time, congenital
      combined nevus may show clinical and dermoscopic changes in size, color, and
      structure. Surgical excision is recommended when clinical and dermoscopic
      features are equivocal and the diagnosis of melanoma cannot be ruled out.

PMID- 16416619
TI  - Treatment of unusual vascular lesions: usefulness of sclerotherapy in
      lymphangioma circumscriptum and acquired digital arteriovenous malformation.
AB  - BACKGROUND: Sclerotherapy is used in venous malformations and hemangiomas, as
      well as chronic venous insufficiency and hemorrhoids. OBJECTIVE: To report on the
      usefulness of sclerotherapy in the treatment of unusual vascular lesions, such as
      lymphangioma circumscriptum and acquired digital arteriovenous malformation.
      METHODS: Two unusual cases were treated with a sclerosant, sodium tetradecyl
      sulfate. RESULTS: The patients were almost cleared with several treatments of
      sclerotherapy. CONCLUSION: Sclerotherapy can be recommended as an effective
      treatment method for unusual vascular lesions, such as lymphangioma
      circumscriptum and acquired digital arteriovenous malformation.

PMID- 16416620
TI  - Erythroplasia of Queyrat with urethral involvement: treatment with carbon dioxide
      laser vaporization.
AB  - BACKGROUND: Erythroplasia of Queyrat is an uncommon carcinoma in situ that
      usually arises on the mucosa of the glans penis or prepuce as red, shiny, sharply
      demarcated velvety plaques. The treatment is often difficult and associated with
      significant recurrence rates, especially in cases with urethral involvement.
      OBJECTIVE: To evaluate carbon dioxide laser treatment in a case of erythroplasia
      of Queyrat with urethral involvement. MATERIALS AND METHODS: We report a patient
      with erythroplasia of Queyrat involving the urethra who was treated with carbon
      dioxide laser vaporization. RESULTS: Treatment with carbon dioxide laser
      vaporization resulted in an excellent cosmetic and functional status outcome for
      the glans penis and urethral lesions. CONCLUSION: Carbon dioxide laser
      vaporization is probably the initial elective treatment for erythroplasia of
      Queyrat with urethral involvement in young immunocompetent patients. A follow-up
      is necessary, and new sessions of treatment should be quickly performed if
      recurrence occurs.

PMID- 16416621
TI  - Mohs surgical extirpation of a basal cell carcinoma in a patient with familial
      multiple trichoepitheliomas.
AB  - BACKGROUND: The success of Mohs surgery relies on the ability to histologically
      differentiate tumor from the normal background tissue of the patient. In most
      cases of basal cell carcinoma and nonmelanoma skin cancer, this is a relatively
      straightforward process. However, in distinction, when only subtle
      histopathologic features differentiate the background tissue from the tumor of
      interest, the determination of a tumor-free margin becomes more challenging.
      OBJECTIVE: Our objective is to highlight the histopathologic features that we
      used to differentiate our patient's near-confluent background of
      trichoepitheliomas from the basal cell carcinoma that we were extirpating.
      METHODS: Case report. RESULTS: A 41-year-old white female with a history of
      familial multiple facial trichoepitheliomas presented for removal of a basal cell
      carcinoma on her right lower cutaneous lip. Mohs surgery was used to remove the
      tumor. The characteristic features of basal cell carcinoma and trichoepithelioma
      were used to differentiate the basal cell carcinoma that we were removing from
      the surrounding trichoepitheliomatous neoplasia. CONCLUSION: Mohs surgical
      extirpation of a basal cell carcinoma in a patient with multiple familial
      trichoepitheliomas requires a clear understanding of the histopathologic features
      that differentiate a trichoepithelioma from a basal cell carcinoma.

PMID- 16416622
TI  - Mohs micrographic surgery for squamoid eccrine ductal carcinoma.
AB  - BACKGROUND: Squamoid eccrine ductal carcinoma is a rare cutaneous malignancy.
      There are no accepted standards for surgical margins in eccrine carcinomas.
      OBJECTIVE: We report a case of squamoid eccrine ductal carcinoma resembling
      squamous cell carcinoma and discuss Mohs micrographic surgery as a surgical
      modality for eccrine carcinomas. METHOD: The patient was a 30-year-old Korean
      woman with a 4-year history of a nodule on her neck. Following primary diagnosis
      of squamous cell carcinoma by punch biopsy, the tumor was completely removed by
      Mohs micrographic surgery with a 2 mm cancer-free margin. RESULT: A one-stage
      Mohs micrographic surgical procedure was performed, and the size of the tumor
      mass was 2.3 x 2.5 cm in width and 1.5 cm in depth. On histopathologic
      examination, the tumor was characterized by both eccrine and squamous
      differentiation. The squamous cells expressed epithelial membrane antigen and
      cytokeratin 5 and 6, and the cells forming ductal structures expressed anti
      carcinoembryonic antigen. Although eccrine carcinomas show a generally aggressive
      clinical course, the patient was disease free at 14 months after surgery.
      DISCUSSION: Squamoid eccrine ductal carcinoma should be considered in the
      differential diagnosis of squamous cell carcinoma and other cutaneous adnexal
      neoplasms showing squamoid and ductal features of differentiation. In addition,
      Mohs micrographic surgery can be an option sufficient for complete surgical
      removal of eccrine carcinomas such as squamoid eccrine ductal carcinoma.

PMID- 16416623
TI  - Severe complete pachydermoperiostosis (Touraine-Solente-Gole syndrome).
AB  - BACKGROUND: The thickened, folded skin of Touraine-Solente-Gole syndrome
      (pachydermoperiostosis) can result in cosmetic and fuctional deformities.
      OBJECTIVE: To illustrate that simple surgical procedures can improve cosmetic and
      functional status. METHODS: Case report of a 33-year-old male with bilateral
      eyelid ptosis, enlargement of the eyelids, and a leonine facies owing to deep
      skin furrows managed with bilateral blepharoplasties and tarsal wedge resections,
      along with excision of multiple skin furrows. RESULTS: A greatly improved
      cosmetic appearance was achieved with these standard procedures. CONCLUSIONS: The
      appearance of patients with pachydermoperiostosis can be greatly improved with
      standard surgical procedures.

PMID- 16416624
TI  - Aggressive and neglected basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy
      and usually has a benign coarse. Rarely, examples of aggressive and neglected
      types of this tumor are seen. OBJECTIVE: To present an interesting and dramatic
      example of how some people neglect their tumors and how devastating the sequelae
      can be. METHODS: We report a 58-year-old man with an extensive BCC and signs of
      cranial nerve involvement. RESULTS: The patient had a large, infected ulcer on
      his scalp. He also had skull bone destruction, osteomyelitis, mastoiditis,
      cranial nerve paralysis, and radiographic features of the skull base and upper
      cervical soft tissue involvement. Pathologic studies revealed an infiltrating
      form of BCC. CONCLUSIONS: If left untreated and neglected, as in this case, BCC
      can become inoperable and complicated.

PMID- 16416625
TI  - Microcystic adnexal carcinoma involving a large portion of the face: when is
      surgery not reasonable?
AB  - BACKGROUND: We report a case of microcystic adnexal carcinoma (MAC) involving a
      large portion of the face, one of the largest of any MAC reported thus far in
      this area, and review the literature regarding the nature of the tumor and
      available treatments. We also review all of the reported cases of metastases and
      the possible role of radiation in the etiopathogenesis of this tumor. OBJECTIVE:
      To review the literature about what is known about therapy for MAC and what
      options are available to patients who have this disease. MATERIALS AND METHODS:
      Case report and review of the literature. RESULTS: Of the 274 cases of MAC thus
      far reported, there are 6 cases of metastases, only 1 of which resulted in death.
      CONCLUSION: Mohs surgery should be the treatment of choice for this tumor;
      however, when extirpation entails sufficiently large morbidity, given the low
      rate of metastases and mortality, observation is a reasonable alternative.

PMID- 16416626
TI  - Decreased efficacy of topical anesthetic creams in presence of benzoyl peroxide.
AB  - BACKGROUND: Topical anesthetics are widely used to diminish the sensation of pain
      from various medical cutaneous procedures. Any topical agent that reduces the
      desired effect has clinical ramifications. MATERIALS AND METHODS: Topical 6%
      benzocaine cream was applied to both inner forearms of five persons and covered
      with a bandage. One of the arms was additionally treated simultaneously with 5%
      benzoyl peroxide. The areas were tested with a pinprick examination every 10
      minutes for the ensuing hour. RESULTS: There was an estimated 75% increased
      perception of pain on the forearm to which benzoyl peroxide was applied in
      consort with the topical anesthetic at all examination times. CONCLUSIONS:
      Benzoyl peroxide chemically reacts with topical anesthetics such as tetracaine,
      procaine, pramoxine, prilocaine, and lidocaine, causing a significant reduction
      in their numbing effect. Clinically, make sure that the skin area to be topically
      anesthetized is devoid of any previous treatment with benzoyl peroxide or insist
      that the skin is thoroughly washed prior to application of the anesthetic.

PMID- 16416627
TI  - To the editor: incompletely excised basal cell carcinoma treated with 5%
      imiquimod cream.

PMID- 16416628
TI  - To the editor: effect of single pulsed dye laser treatment on acne vulgaris.

PMID- 16416629
TI  - Minimally invasive esthetics: my life's journey.

PMID- 16416630
TI  - Fat autograft muscle injection (FAMI): new technique for facial volume
      restoration.
AB  - BACKGROUND: Restoration of depleted facial volume is becoming increasingly
      recognized by cosmetic surgeons as a necessary component of facial rejuvenation.
      Autologous fat has been used for years, but asymmetry and transient duration have
      been problematic. OBJECTIVE: To describe a new procedure called fat autograft
      muscle injection (FAMI), which is designed to maximize the survival of the
      adipocyte by placement within the muscles of facial expression. METHODS: The
      technique involves gentle harvesting of fat and centrifugation for 3 minutes. Fat
      is transferred to 1 cc syringes and attached to one of nine different cannulas
      shaped to conform to musculoskeletal contours. The muscle is injected with 1 to 3
      cc of fat in a retrograde fashion from the insertion to origin or vice versa.
      Each syringe is emptied in one to three passes. The full face or regions of the
      face may be treated. RESULTS: FAMI offers soft, natural rejuvenation of depleted
      facial volume.

PMID- 16416631
TI  - Panfacial volume restoration with fat.
AB  - BACKGROUND: A careful look at the aging face shows it to consist of more than
      loose skin and rhytids. With aging, the face loses its anterior projection, with
      a resultant displacement of skin inferiorly. There is mimetic muscular
      accentuation and an abundance of deep grooves and shadows. In addition, fat
      redistributes in specific patterns in overweight versus lean individuals.
      OBJECTIVE: To restore the three-dimensional projection and overall shape of the
      face to more youthful contours and to eliminate shadowing and muscle to skin
      interactions. METHODS: Autologous fat is harvested with an open-tipped, blunt
      cannula under tumescent anesthesia. It is then transferred to 1 mL syringes for
      injection into the face under local anesthesia. Fat is woven into the deep
      tissues of the face using a small-bore blunt cannula. The entire face is
      addressed by filling one cosmetic unit at a time. Fat is anchored deep to the
      muscles, in the muscles, and subcutaneously depending on the anatomic site and
      desired result. RESULTS: Dramatic changes in contour are achieved with judicious
      placement of fat. Skin redraping and the interruption of muscle to skin
      interactions occur when autologous fat is infiltrated in small aliquots, with
      specific direction at appropriate tissue levels. Complications are rare and minor
      with this technique. CONCLUSIONS: Autologous fat is an excellent tool for
      replacing volume and restoring contour to the aging face.

PMID- 16416632
TI  - Cryopreservation of human fat for soft tissue augmentation: viability requires
      use of cryoprotectant and controlled freezing and storage.
AB  - BACKGROUND: Autologous fat transfer for soft tissue augmentation has been
      increasing in recent years. Graft longevity may vary greatly from patient to
      patient, requiring repeat procedures, often using frozen adipose tissue. Storage
      usually involves placing syringes of fat directly into a -20 degrees C freezer.
      However, the viability of fat frozen in this way is controversial. OBJECTIVE:
      This study tested methods for the optimal storage of adipose tissue harvested by
      tumescent liposuction. MATERIALS AND METHODS: Aliquots of washed adipose tissue
      were frozen directly at -20 degrees C or mixed with cryoprotectants, frozen at 1
      degree C/min, and subsequently stored in liquid nitrogen vapor phase. Aliquots
      were subsequently thawed, and adipocyte viability was determined by staining and
      culture methods. RESULTS: Viability of adipocytes frozen at -20 degrees C was
      very low when analyzed by staining, and no cultures could be established from any
      of the specimens. In contrast, viable adipocytes were recovered from samples that
      were controlled-rate frozen in the presence of cryoprotectants and stored in
      nitrogen vapor. CONCLUSION. Our results indicate that fat frozen at -20 degrees C
      is not viable and thus provides no advantage over inert fillers. The methods here
      described could readily be transferred to the clinical setting after further
      laboratory study.

PMID- 16416633
TI  - Facial volumetric correction with injectable poly-L-lactic acid.
AB  - BACKGROUND: Polymers of lactic acid'have been widely used for many years in
      different types of medical devices, such as resorbable sutures, intrabone
      implants, and soft tissue implants. Injectable poly-L-lactic acid (PLLA;
      Sculptra), a synthetic, biodegradable polymer, has gained widespread popularity
      in Europe for the treatment of facial changes associated with aging. OBJECTIVE:
      To provide background information on injectable PLLA and to describe clinical
      experience with its use in Europe for facial volume enhancement. METHODS:
      Technique varies with site of injection. Generally, the product is implanted
      subcutaneously or intradermally in a series of treatments. No allergy testing is
      required. RESULTS: Based on experience in more than 2,500 patients, injectable
      PLLA has been used successfully for the correction of nasolabial folds, mid- and
      lower facial volume loss, jawline laxity, and other signs of facial aging.
      Correction lasts for 18 to 24 months in most patients. CONCLUSIONS: Injectable
      PLLA treatment provides an excellent and prolonged correction of a variety of
      facial wrinkles, depressions, and laxity with a minimally invasive procedure that
      does not require allergy testing or a recovery period.

PMID- 16416635
TI  - Liquid silicone for soft tissue augmentation.
AB  - BACKGROUND: The use of liquid silicone for soft tissue augmentation has been
      associated with a great deal of controversy and negative publicity. It is hoped
      that this monograph will clarify some of the substantive issues behind the
      controversy. OBJECTIVE: To outline and discuss the history, legal status,
      indications, contraindications, technique, and complications associated with the
      use of liquid silicone for soft tissue augmentation. METHODS: Impressions derived
      from a 22-year experience involving the treatment of over 3000 patients using
      liquid silicone are presented, along with data abstracted from the scientific and
      the lay literature. CONCLUSION: Pure liquid silicone may be superior to any
      currently available agent in properly selected patients for permanent correction
      of certain types of defects. Physicians who use it, however, must be advised that
      the misuse of this agent or other materials masquerading as liquid silicone have
      created a pervasive climate of distrust and a veritable minefield of
      extraordinarily unpleasant medicolegal possibilities.

PMID- 16416634
TI  - HIV facial lipoatrophy: causes and treatment options.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-associated facial lipoatrophy is
      becoming epidemic and may seriously affect quality of life. OBJECTIVE: To review
      the possible causes and treatment options for HIV facial lipoatrophy. METHODS:
      This article is based on a review of the medical literature and the author's
      clinical experience in treating HIV facial CONCLUSION: Although absorbable
      injectable fillers and implants are helpful in treating HIV facial lipoatrophy,
      they are limited by cost and the short duration of correction. Newer forms of
      longer-lasting fillers (poly-L-lactic acid [Sculptra]) and permanent injectable
      fillers (liquid injectable silicone) are proving useful for treatment of this
      condition.

PMID- 16416636
TI  - Treatment of acne scars with liquid silicone injections: 30-year perspective.
AB  - BACKGROUND: This article addresses the use of liquid injectable silicone as both
      an immediate and long-lasting treatment for broad-based, depressed acne scars.
      The only filler substance that maintains precision and permanence in improving
      and/or correcting these types of acne scar defects is medical-grade liquid
      silicone. OBJECTIVE: We describe five patients with a history of acne scarring
      who showed improvements from injections of liquid silicone at the initial
      treatment session and lasting over a 10-, 15-, and 30-year follow-up period.
      METHODS: Monthly liquid silicone injections using a technique known as the
      microdroplet, multiple-injection approach. RESULTS: This article documents the
      safety, effectiveness, and precision of silicone in addition to highlighting the
      fact that its permanence is what distinguishes it from other filler materials.
      CONCLUSION: As a precise and permanent filling substance used for soft tissue
      augmentation, liquid injectable silicone can improve and/or eliminate depressed,
      broad-based acne scars through a technique known as the microdroplet, multiple
      injection

PMID- 16416637
TI  - Ten-year experience using injectable silicone oil for soft tissue augmentation in
      the Philippines.
AB  - BACKGROUND: No ideal, permanent filler is approved by the U.S. Food and Drug
      Administration. Repeated injections of new temporary fillers make this cosmetic
      procedure expensive. OBJECTIVE: To show that silicone oil is effective, safe,
      economical, and permanent. MATERIALS AND METHOD: The age, sex, number,
      indications, sites, adverse reactions, total amounts injected, and clinical
      cosmetic results of 206 cases were tallied. RESULTS: Females (82%) outnumbered
      males (18%). The majority were in the 21- to 30-year age group. Fifty-five
      percent had acne scars, 42% nasolabial grooves, 13.5% marionette lines, 12.6%
      glabellar lines, 9.8% postvaricella scars, 9.3% inframalar depressions, 1.8% post
      traumatic scars, 1.4% lipodystrophy, 1% lip augmentation, 0.9% sleep lines, and
      0.4% contour defect. Fifty-one percent had < or = 0.5 cc, 22% 1 cc, 7% < or = 1.5
      cc, 7% < or = 2 cc, and 12% >2 cc. Clinical improvement was graded excellent (76
      100%), good (50-75%), fair (26-50%), and poor (< 25%). Seventy-two percent had
      excellent results, 18% good, 2% fair, and 0.5% poor. Seven percent were lost to
      follow-up. Two percent (n=5) had transient erythematous papules lasting 2 to 6
      weeks, with the exception of two patients. CONCLUSION: Silicone oil injected with
      the correct indications and techniques and with microdroplet injections is a
      safe, economical, and permanent dermal and subcutaneous filler. Rare permanent
      erythematous papules and transient ecchymoses appear on deep dermal injections.

PMID- 16416639
TI  - Polymethylmethacrylate microspheres/collagen as a tissue augmenting agent:
      personal experience over 5 years.
AB  - BACKGROUND: Polymethylmethacrylate microspheres/collagen has been used in Canada
      since 1998. A closely related product will probably be approved in the United
      States shortly. Concerns have been expressed about the use of permanent fillers
      such as this. OBJECTIVE: This retrospective study of the authors' clinical
      practice is designed to reflect their experience with this agent. In particular,
      the authors describe some of the problems they have seen. RESULTS:
      Polymethylmethacrylate microspheres/collagen has behaved as a satisfactory long
      term tissue augmenting agent in the authors' practice. They have had the
      opportunity of managing any number of patients with Artecoll granulomas and
      describe these patients. CONCLUSION: When polymethylmethacrylate
      microspheres/collagen is introduced to the United States, practitioners will need
      to learn how to use this exacting agent and will obtain excellent results with
      careful use.

PMID- 16416638
TI  - Injectable silicone and the foot: a 41-year clinical and histologic history.
AB  - BACKGROUND: Since 1964, the author has investigated injectable liquid silicone as
      a soft tissue substitute for the loss of plantar fat. This form of fatty tissue
      depletion over the sole is closely linked to a common painful weight-bearing foot
      disorder, metatarsalgia, and to painless diabetic foot ulcers. OBJECTIVES: To
      present the history of injectable silicone, corporate interest, individuals who
      helped pursue approval, its misuses, and events that have delayed its
      availability. MATERIALS AND METHODS: Dow Corning Corporation's 360 Medical Fluid
      of 350 centistoke was injected beneath corns and calluses in 1585 patients.
      Diabetic neuropathic foot ulcers were injected after healing in an effort to
      prevent their recurrence. Surgical and postmortem specimens were gathered for
      histologic analysis. RESULTS: There was no evidence of significant adverse
      response in long-term clinical follow-up. Silicone specimens studied by two
      departments of pathology found no inflammation, infection, allergy, or
      granulomas. CONCLUSIONS: Medical Fluid silicone appears to be safe, effective,
      and stable biomaterial for treating weight-bearing loss of plantar fat.
      Trademarked PodiSil (Richard-James Inc., Peabody, MA, USA), a 350-centistoke
      injectable silicone has been approved for marketing in Europe for the prevention
      of diabetic foot ulcers.

PMID- 16416640
TI  - Artecoll: the Arizona experience and lessons learned.
AB  - BACKGROUND: Artefill is one of several new materials being introduced to the U.S.
      market as a soft tissue augmenting agent. OBJECTIVE: The objectives were to
      evaluate the safety and efficacy of injecting Artecoll (Rofil Medical
      International Breda, the Netherlands) in facial wrinkles compared with injecting
      Zyderm or Zyplast (INAMED, Santa Barbara, CA, USA) and discuss the practical
      lessons learned. METHODS: Thirty-eight patients were randomly selected to receive
      Artecoll or Zyderm/Zyplast into facial defects. Wrinkles were evaluated by the
      treating physician, the subject, and masked physician evaluators. Similar
      evaluations were performed on several collagen patients crossing over to
      Artecoll. Adverse reactions were recorded. RESULTS. All evaluators felt Artecoll
      to be superior to collagen in all treated areas except for the glabella and upper
      lip lines. In these areas, differentiation by photographs between the two
      products became more difficult for the masked evaluators. The adverse side
      effects of Artecoll were almost equal with those of collagen, but most were of
      minimal consequence. Three patients developed persistent nodules (all in perioral
      sites), which were treatable with intralesional steroids. CONCLUSION. Artecoll
      treatment of wrinkles and folds was found to be effective, long lasting, safe,
      and associated with a high percentage of patient acceptance. There is a learning
      curve in injecting this thicker, more permanent product.

PMID- 16416641
TI  - Lip augmentation with liquid silicone.
AB  - BACKGROUND: Many fillers have been used to augment the lips. One of these that
      has provided long-term satisfactory results is liquid silicone. OBJECTIVE: To
      demonstrate the efficacy and safety of lip augmentation with liquid silicone.
      METHOD: Following a discussion of the benefits and risks of the procedure and the
      benefits and risks of alternatives and after answering all of the patients'
      questions, an informed consent form was signed. After obtaining anesthesia with a
      regional nerve block of the infraorbital and mental nerves, 0.25 to 0.5 cc of
      liquid silicone (1,000 centistokes) was injected using the microdroplet technique
      into the vermilion border of both the upper and lower lips. Depending on the
      desire of the patient, the procedure was repeated monthly. The augmentation of
      the lips was documented with histology, micrometry, and digital photography.
      RESULTS: Lip augmentation was achieved gradually during the months following
      liquid silicone injections into the vermilion border of the lips in the 608
      patients studied. Most of the patients requested a second and third injection
      session. The results were most dramatic in the patients with type I and type II
      lips and less satisfactory in patients with type III lips. Bruising occurred in
      the majority of the patients. Eleven patients (2%) developed small palpable
      granulomas. These granulomas either required no treatment, responded to steroid
      injections, or were excised. CONCLUSION: The use of liquid silicone remains an
      effective method of lip augmentation. It returns the adolescent vermilion curl to
      the lips.

PMID- 16416642
TI  - Clinical comparison between two hyaluronic acid-derived fillers in the treatment
      of nasolabial folds: hylaform versus restylane.
AB  - BACKGROUND: Hyaluronic acid-derived injectible fillers are ideal to reduce the
      appearance of nasolabial folding because their effect is relatively long-lasting,
      the material is malleable and easy to use, and there is a very low incidence of
      allergic reaction. OBJECTIVE: To compare the tolerability and efficacy of two
      commercially available hyaluronic acid-based fillers, Hylaform (INAMED
      Aesthetics, Inc., Santa Barbara, CA, USA) and Restylane (Medicis Pharmaceutical
      Corporation, Scottsdale, AZ, USA), in the treatment of nasolabial folds. METHODS:
      Eight healthy adult female subjects underwent filler injection therapy for tissue
      augmentation of their nasolabial folds. Each subject was randomized to receive
      Restylane 0.7 mL to either the right or the left nasolabial fold and Hylaform 1.0
      mL to the contralateral side. High-quality digital photography was performed both
      at baseline and at 12 weeks post-treatment. These photographs were assessed by
      four blinded, independent dermatologist reviewers for improvement. Subjects
      completed questionnaires to document tolerability and satisfaction. RESULTS: All
      subjects found the procedure to be tolerable and completely pain free after the
      use of oral infraorbital regional anesthesia blocks. The average subject
      satisfaction score was 3.00 of 5 for Hylaform and 3.78 of 5 for Restylane. The
      blinded, independent reviewer panel attributed an average improvement score of
      2.86 of 5 for Hylaform and 3.78 of 5 for Restylane. CONCLUSION: Both Hylaform and
      Restylane are effective fillers for tissue augmentation of the nasolabial folds.
      Restylane demonstrated higher efficacy and subject satisfaction than Hylaform.
      With regional nerve blocks prior to injection, both agents are completely
      painless.

PMID- 16416643
TI  - Randomized, double-blind comparison of the efficacy of two hyaluronic acid
      derivatives, restylane perlane and hylaform, in the treatment of nasolabial
      folds.
AB  - BACKGROUND: Cross-linked hyaluronic acid gels may offer longer-lasting cosmetic
      correction and a lower risk of immunogenicity than other soft tissue augmentation
      agents. OBJECTIVE: To compare the efficacy and safety of a non-animal-stabilized
      hyaluronic acid gel (Restylane Perlane, Q-Med, Uppsala, Sweden) with that of a
      hylan B gel (Hylaform, Genzyme Corp., Cambridge, MA, USA), a cross-linked
      hyaluronic acid from chicken combs, for treatment of nasolabial folds. METHODS:
      One hundred fifty patients with moderate or severe nasolabial folds were
      randomized to contralateral treatment with Restylane Perlane and Hylaform.
      Efficacy was assessed using semi-objective outcome instruments at 3, 4.5, and 6
      months after achievement of an "optimal cosmetic result". Patients subsequently
      underwent open-label bilateral retreatment with Restylane Perlane (if required)
      and were followed up for a further 6 months. RESULTS: The two products were
      equally effective in producing an optimal cosmetic result, although fewer
      treatment sessions were required with Restylane Perlane. At 6 months post
      treatment, a higher proportion of patients showed a > or = 1-grade improvement in
      Wrinkle Severity Rating Scale (WSRS) score with Restylane Perlane (75%) than with
      Hylaform (38%). Restylane Perlane was considered superior in 64% of patients,
      whereas Hylaform was superior in 8% of patients. Treatment-related adverse events
      tended to be more frequent with Restylane Perlane. Local injection-site reactions
      were generally transient and mild or moderate in intensity and were no more
      frequent after Restylane Perlane retreatment. CONCLUSIONS: Restylane Perlane
      provides a more durable esthetic improvement than Hylaform and offers acceptable
      tolerability.

PMID- 16416644
TI  - In search of the perfect lip: 2005.

PMID- 16416645
TI  - Facial sculpting and tissue augmentation.
AB  - BACKGROUND: Until recently, deep facial sculpting was exclusively the domain of
      surgical interventions. Recent advances in the available array of dermal and
      subdermal fillers combined with an esthetic appreciation by both surgeons and
      nonsurgeons alike of the positive effect of filling the volume-depleted face have
      led to an expansion in the indications for the use of soft tissue augmenting
      agents. METHOD: Subdermal support of the lateral two-thirds of the brow, the
      nasojugal fold, the malar and buccal fat pads, the lateral lip commissures, and
      the perioral region, including the pre-jowl sulcus, all restore youthful facial
      contour and harmony. An important advance in technique is the subdermal rather
      than the intradermal injection plane. RESULTS: "Instant" facial sculpting giving
      a brow-lift, cheek-lift, lip expansion, and perioral augmentation is possible
      using modern soft tissue augmenting agents. The softer, more relaxed appearance
      contrasts to the somewhat "pulled" appearance of subjects who have had surgical
      overcorrections. Treatments can be combined with botulinum toxin and other
      procedures if required. CONCLUSION: Newer advances in the use of fillers include
      the use of fillers injected in the subdermal plane for "lunchtime" facial
      sculpting. Using the modern esthetic filler compounds, which are biodegradable
      but longer lasting, subjects can have a "rehearsal" treatment or make it ongoing.
      Some individuals, such as those with human immunodeficiency virus (HIV)-related
      lipoatrophy or those who desire to obtain a longer-lasting effect, may elect to
      use a nonbiodegradable filling agent.

PMID- 16416646
TI  - Who is still using expanded polytetrafluoroethylene?
AB  - BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) is a permanent, solid
      implant that has been used for facial soft tissue augmentation. The implants are
      generally used in the lower third of the face for filling lips, nasolabial folds,
      and deeper facial lines. Many physicians have noted complications with this use.
      OBJECTIVE: To determine physician satisfaction trends for ePTFE. METHODS. A
      physician satisfaction survey was sent out in February 2000. Information
      regarding perceived patient and physician satisfaction regarding favored sites
      for the use of augmentation with ePTFE, the quantity used, and revision rates was
      assessed. A second survey was mailed in July 2003 to the same physicians to gain
      information regarding long-term satisfaction with ePTFE. RESULTS: The results
      from the first survey revealed that 10 of 12 physicians perceived that their
      patients were satisfied with ePTFE implants in all locations with the exception
      of the lips. There was a wide variation in the number of cases of ePTFE performed
      per year among the different physicians. Reported revision rates varied from less
      than 1 to 100% in the lips. The majority of the physicians found that removal of
      the implant was easy. The results from the second survey in 2003 revealed that
      100% of the physicians were disappointed with these products. Physicians'
      assessments of their patients' satisfaction revealed that one-third were mildly
      disappointed and two-thirds were satisfied. Revision rates in all cases were
      increased between the first and second survey. A subjective patient satisfaction
      survey was not done during either of these time periods. CONCLUSIONS: New
      procedures are often quickly embraced by both physicians and patients. It is
      crucial that we reevaluate and report long-term experience and satisfaction.
      Although this informal survey has limitations, it appears that some physicians
      are less satisfied with ePTFE as a soft tissue implant. Larger studies including
      objective measurements delineating the degree of improvement and subjective
      patient satisfaction would be welcomed.

PMID- 16416647
TI  - Adverse reactions to dermal fillers: review.
AB  - BACKGROUND: For many patients, injectable filling agents offer the promise of
      facial rejuvenation while offering reduced risks compared with more invasive
      surgery. With the increase in products available and the rise in the number of
      patients seeking this type of intervention, it is crucial that both the physician
      and the patient are fully cognizant of the risks involved with each product.
      OBJECTIVE: To review the incidences and types of reaction to various commonly
      used injectable products. METHODS: A literature review and personal experiences
      (gained largely in Europe over the past 8 years) of dermal fillers from 1996 to
      the present, including illustrative case reviews. RESULTS: Reactions can be
      attributed to the procedure itself, the procedural technique, and the agent
      injected. Some of these reactions are preventable, whereas others are inevitable;
      most are mild and transient. Improving product formulations, altering the
      concentration of product injected, or changing the injection technique can
      dramatically reduce the incidence of adverse reactions. Since its reformulation
      in mid-1999, the biologically engineered hyaluronic acid filler Restylane
      (Medicis Pharmaceuticals, Scottsdale, AZ, USA) elicits less than one allergic
      reaction in 1600 treatments. Skin reactions with poly-L-lactic acid (New
      Fill/Sculptra, Dermik Laboratories, Berwyn, PA, USA) are considerably less likely
      if a greater dilution and deeper injection technique are employed. CONCLUSION:
      Different injectable products have highly divergent properties, associated risks,
      and injection requirements. The dermasurgeon should be suitably experienced to
      select and use these products correctly.

PMID- 16416648
TI  - Complications of fillers: overview.
AB  - BACKGROUND: Avoiding complications requires thorough training and medical,
      anatomic, and esthetic common sense. Complications can occur as a function of
      anatomic location, technique deficiencies, the type of defect treated,
      identifiable host factors, infectious processes, and allergies as a consequence
      of intrinsic characteristics of any particular filler. They can also occur in the
      absence of any identifiable host factors and flawless technique. Complications
      following temporary fillers often occur soon after augmentation, may resolve
      spontaneously, and are usually easy to treat. Conversely, complications that
      occur after using permanent or semipermanent fillers can appear months to years
      after augmentation and prove very difficult to treat. OBJECTIVE: To analyze and
      describe complications that have occurred following soft tissue augmentation and
      to present strategies for avoiding, recognizing, and treating them. METHODS:
      Protocols and observations derived from a 24-year experience using a wide variety
      of soft tissue augmenting agents are presented in association with pertinent
      clinical literature. Characteristic complications associated with specific types
      of soft tissue augmenting agents are presented in tabular form. CONCLUSION:
      Tissue fillers offer patients an opportunity for instant gratification with
      minimum downtime and, in general, an extremely favorable risk-to-benefit ratio.
      The best way to minimize complications in both your patients and yourself is to
      avoid them.

PMID- 16416649
TI  - Human collagen reactions.

PMID- 16416650
TI  - Five percent lidocaine cream applied simultaneously to the skin and mucosa of the
      lips creates excellent anesthesia for filler injections.
AB  - BACKGROUND: Injection of filler substances into the lips is painful, and many
      patients also find the injection of local or regional anesthesia into the lips
      painful. OBJECTIVE: To develop a highly effective and painless form of anesthesia
      to facilitate injection of filler substances into the lips. METHODS: Five percent
      lidocaine cream was applied simultaneously to the skin, vermilion, and mucosa of
      the lips (with the use of a barrier to keep the cream in contact with the mucosa
      and out of the rest of the mouth) for 20 to 30 minutes. RESULTS: Profound
      anesthesia of the lips was reliably produced, with no complications. CONCLUSIONS:
      This "anesthetic cream block" is easier to perform and better tolerated than
      injectable anesthetics. Use of this technique is likely to expand the range of
      physicians who perform filler injections on the lips and will probably also
      expand the range of patients who wish to have filler injections done on their
      lips and who (because they had little or no discomfort) are willing to return for
      additional filler injections in the future.

PMID- 16416651
TI  - Economic justification for a public school of pharmacy: lessons for Nevada.
AB  - There is a nationally recognized shortage of pharmacists in the United States
      that is more pronounced in the West. This shortage will worsen with the rapid
      growth and aging of the population. Demand for traditional pharmaceutical care
      services has grown faster in the last decade than predicted and is projected to
      outpace the entry of pharmacists into the workforce. The growth of direct patient
      care roles for pharmacists, together with the increasing need for pharmacist
      services in the management of health care, threatens to overpower the present
      capacity of pharmaceutical education. Healthcare officials and consumers alike
      are becoming increasingly concerned about the pressure on pharmacist services
      leading to decreased access to pharmaceutical care and an increase in the
      frequency of medication errors both having a major impact on the health of
      patients. While the impact of the pharmacist shortage on the quality of
      pharmaceutical care has been the subject of recent concern, the role of
      pharmacists in economic development has not been adequately addressed. In this
      review, we examine the impact of the shortage of pharmacists and apply economic
      principals to the impact created by the addition to a state economy of a public
      school of pharmacy. We apply this analysis to the proposed addition of a public
      school of pharmacy in Nevada, the fastest growing state in the nation, which
      currently has a single, private pharmacy school.

PMID- 16416652
TI  - Participation of epidermal langerhans cells in human pathology and their
      potential as targets for drug development: a review of literature.
AB  - Langerhans cells (LC) are antigen presenting cells of the epidermis originated
      from bone marrow progenitors that arrive into the epidermis through the blood
      vessels LC are also referred to as dendritic cells. In the presence of antigens
      LC become activated and migrate from the skin to the lymph nodes where they
      induce T cells responses, therefore, LC function as sentinels of the epidermis
      and constitute, in part the Skin Immune System (SIS). LC have been implicated in
      the pathogenesis and pathophysiology of diverse diseases such as atopic
      dermatitis, alopecia areata, human immunodeficiency virus infection (HIV) and
      melanoma, among others. The aim of this review is to draw the attention of
      pharmacologists towards LC as targets for drug action and drug development due to
      their immunesurveillance function. LC modulate the SIS as an endogenous mechanism
      of defense against many infectious agents, xenobiotics, and for the treatment of
      cancer, infections, and autoimmune diseases. A review of the literature on LC is
      presented here giving emphasis to LC cell cycle and cellular and molecular
      characteristics, LC possible role in human pathologies, and LC therapeutic
      potential.

PMID- 16416653
TI  - Polyamines, their biochemistry and role in neoplasia.

PMID- 16416654
TI  - Significance of targeting polyamine metabolism as an antineoplastic strategy:
      unique targets for polyamine analogues.
AB  - The polyamines, putrescine, spermidine, and spermine, are naturally occurring
      polycationic alkylamines that are absolutely required for eukaryotic cell growth.
      Importantly, the polyamine metabolic pathway, as well as the requirement of
      polyamines for cell growth, is frequently dysregulated in cancer cells, thus
      providing a unique set of targets for therapeutic intervention. Ornithine
      decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis, is
      frequently up-regulated in preneoplastic cells, and has been implicated as an
      oncogene in multiple tumor types. Several model systems have demonstrated that
      inhibition of ODC's enzymatic activity and down-regulation of its expression are
      rational strategies for both chemotherapy and chemoprevention. Specific
      inhibitors of ODC, most notably 2-difluoromethylornithine (DFMO), have been used
      experimentally to validate polyamine metabolism as an antineoplastic strategy.
      However, multiple biochemical and clinical limitations to these ODC-targeting
      strategies minimize their value as therapeutic tools. Included among these
      limitations are poor bioavailability of the inhibitor, and the compensatory up
      regulation of polyamine metabolism and transport that allow tumor cells to escape
      the growth inhibitory effects of blockers specifically targeting ODC. As a
      strategy to overcome the limitations of direct enzyme inhibition, several groups
      have pursued the design of polyamine analogues that specifically target the
      dysregulated polyamine metabolism found in tumors. These analogues have been
      developed specifically to target the specific polyamine transporter, thus
      competing with circulating natural polyamines. Additionally, most of the
      analogues examined thus far maintain the regulatory function of the natural
      polyamines, but are unable to functionally substitute for them in promoting
      growth. Specifically, individual analogues have demonstrated the ability to down
      regulate each of the biosynthetic enzymes without causing compensatory increases
      in parallel systems or increases in polyamine uptake. Additionally, specific
      analogues produce tumor specific up regulation of the rate-limiting enzymes in
      polyamine catabolism. These results are particularly significant in that the
      products of polyamine catabolism, including H2O2, have been demonstrated to
      participate in the tumoricidal activity of specific analogues.

PMID- 16416655
TI  - Emerging concepts in GPCR function--the influence of cell phenotype on GPCR
      pharmacology.
AB  - G protein coupled receptors (GPCRs) are an important class of ligand-activated
      proteins that regulate cellular metabolism. It is now appears that GPCR function
      is highly dependent upon the cellular environment in which it is expressed.
      Indeed, the cell phenotype influences several sequelae of GPCR activation,
      including GPCR oligomerization, G protein coupling, spatial organization of
      signaling proteins and inactivation and internalization processes. The cell
      phenotype, consequently, modulates both the affinity and efficacy of endogenous
      agonists and synthetic compounds. Emerging data suggests a complex function of
      GPCR signaling resulting in tissue specific responses, even those emanating from
      the same GPCR subtype. This short review describes some phenotypic influences on
      GPCR function and their implications for the use of cell-based assays used to
      identify and characterize GPCR ligands.

PMID- 16416656
TI  - The angiotensin-II (AT-II) receptor blocker olmesartan reduces renal damage in
      animal models of hypertension and diabetes.
AB  - The development of angiotensin receptor blockers (ARBs) has resulted in effective
      oral treatment for hypertension. One of the most recent members of this
      therapeutic class is olmesartan medoxomil (OM). The active metabolite,
      olmesartan, produces insurmountable AT1 receptor blockade and dose-dependently
      reduces BP. In both experimental and clinical studies, ARBs have been shown to
      exert renoprotective effects in addition to antihypertensive activity. In an SHR
      model of hypertensive renal injury, OM (3.0 and 10.0 mg/kg/day) dose-dependently
      reduced BP but also reduced urinary protein excretion by 65% and 75%,
      respectively (P < 0.05). Similar doses of OM, in a DOCA-salt hypertensive rat
      model, did not affect BP but reduced urinary protein excretion by 26% and 39%
      when compared to control hypertensive animals (P < 0.05). Hypertension is a major
      pathophysiological determinant of progressive arterial damage that can accelerate
      the development of diabetic nephropathy. At doses of 0.6 and 6.0 mg/kg/day, OM
      significantly reduces hypertension associated with type 2 diabetes. These doses
      of OM reduced BP and dose-dependently reduced proteinuria 31% and 76%,
      respectively, in hypertensive ZDF rats (P < 0.01). OM also reduced renocortical
      and renomedulla injury by 19% and 50% at doses of 0.6 and 6.0 mg/kg/day. The
      glomerular sclerosis index (GSI) was also reduced by 25% and 37% (P < 0.05).
      Thus, OM improves both functional and morphologic damage associated with diabetic
      nephropathy. These studies demonstrate that OM, a potent ARB, dose-dependently
      reduces BP and also provides a dose-related nephroprotective effect in animal
      models of diabetes. These studies show that the antihypertensive affect of OM is
      renoprotective but suggest that these renal benefits may also occur independently
      from a reduction in BP. A further evaluation of the effects of OM in diabetes is
      warranted.

PMID- 16416657
TI  - In vitro translation and computational analyses of human profilin multimers.
AB  - Profilin is an ubiquitous intracellular G-actin and PIP2-binding protein that is
      a pan-allergen. Functional native human profilin multimers have recently been
      described, implicating regulatory roles in cell morphology, signaling and
      allergies. Considering the potential importance of profilin self-association in
      nature, multimerization was examined using cDNAs to human profilin I (P1) and II
      (P2) by employing a plasmid (pCITE2a+) for in vitro transcription/radiolabeled
      translation. Autoradiography of affinity column purified 35S-met-P1 or -P2
      revealed predominant -14.8, 30 and 58 kDa bands that corresponded to parallel
      immunoblots using rabbit anti-human profilin antibodies. Reducing agents had no
      significant effect on the ratios of cpm associated with gel slices corresponding
      to 14.8/30/58 kDa profilin bands. Computer-based molecular modeling was used to
      further analyze a hypothetical structure for profilin multimers resistant to
      reducing agents. The crystalline P1 structure was downloaded and analyzed for
      likely sulphydryl bonding via the three integral cysteines (C16, C70, C127). All
      possible combinations of SH-bonds were investigated. The energetically most
      favorable dimer involved C16 + C127. 3-Dimensional conformation also revealed a
      protective pocket around the S-S bonds. The data show that, similar to native
      human and plant profilins, P1 and P2 cDNAs encode proteins that form fastidious
      multimers. A structure is proposed with relatively protected disulfide bridges
      between individual profilin moieties consistent with existing biochemical data.

PMID- 16416658
TI  - Expression of stretch-activated potassium channels in human myometrium.
AB  - Using RT-PCR and a semiquantitative method to detect relative differences in mRNA
      expression, we examined uterine smooth muscle from both pregnant and non-pregnant
      women for the expression of members of weak inwardly rectifying 2-pore potassium
      channel family (TWIK), TREK and TRAAK. We show for the first time that TRAAK
      transcript is present in uterine smooth muscle, albeit at relatively low levels.
      The expression of TREK is far more robust. Trek-1 but not TREK-2 was expressed in
      both pregnant and non-pregnant myometrium. Comparison of TREK-1 expression in
      several hysterectomy samples relative to 18S ribosomal mRNA suggested that
      expression may be regulated or could vary from subject to subject since
      expression was not see in some women. A similar result was obtained in pregnant
      samples. When all samples expressing TREK-1 were compared, a significant increase
      in TREK-1 expression was seen in pregnant term tissues from women not in labor.

PMID- 16416659
TI  - Renal vascular responses in an experimental model of preeclampsia.
AB  - In pregnancy there is an attenuated response to vasoconstrictors and pressor
      agents, including Angiotensin II (Ang II). This effect is reverted in
      preeclampsia. We evaluated the renal pressor response induced by Ang II in an
      experimental model of preeclampsia based on the development of feto-placental
      ischemia produced by a subrenal aortic coarctation (SRAC). Dose-response curves
      for Ang II were obtained in an isolated perfused kidney preparation comparing
      groups of SRAC pregnant and non-pregnant rats in the presence and absence of
      losartan (AT1 antagonist) or PD123319 (AT2 antagonist). Kidneys from the
      experimental model of pre-eclampsia showed an enhanced response to AngII. In
      addition, losartan (10 nM) inhibited the vasopressor effect to Ang II in this
      model but not in the control group. PD 123319 (1 nM), increased the response in
      both groups, but the effect was more evident in the pre-eclamptic group. This
      suggests modifications in the relative participation of renal vascular receptors
      AT1/AT2 induced by an experimental model of pre-eclampsia, with an increased
      participation of AT1 and a decreased participation of AT2.

PMID- 16416660
TI  - Selective decrease of Na+/k+ -ATPase activity in the brain of hypothyroid rats.
AB  - The present work was performed in order to know if mild hypothyroidism in rats
      modifies the activity of the Na+/K+ -ATPase in different regions of the brain.
      Male Wistar rats (300-350 g) were randomly divided into three groups: (1) control
      group (n=8) drank tap water. (2) hypothyroid group (n=8) treated with 60 mg/kg of
      methimazole in drinking water; and (3) replaced group (n=8) treated with 60 mg/kg
      of methimazole plus 35 microg/kg of thyroid hormone (T3) in drinking water. After
      four weeks of treatment, the rats of all groups were sacrificed by decapitation.
      The cortex, amygdala, hippocampus and cerebellum were dissected and frozen at -70
      degrees C until assay. For enzymatic assay, the tissues were homogenized. The
      Na+/K+ -ATPase activity was determined by quantifying inorganic phosphate after
      the samples were incubated with ATP in the presence and absence of 1 mM ouabain.
      The Na+/K+ -ATPase activity is expressed as pmoles Pi/hr/mg protein. The results
      showed that the Na+/K+ -ATPase activity in the cortex, amygdala and hippocampus,
      but not in cerebellum, was lower in hypothyroid group than in control group
      (p<0.05). The co-administration of methimazole and T3 avoided the decrease of
      Na+/K+ -ATPase activity, except in amygdala. According to the results obtained we
      concluded that methimazole treatment decreased the Na+/K+- ATPase activity in the
      brain's regions which are related to seizures onset. That decrement in enzyme
      activity was avoided with the coadministration of thyroid hormone.

PMID- 16416661
TI  - Pinacidil increases diclofenac antinociception in the formalin test.
AB  - Evidence suggests that the ATP-sensitive K+ channels are important in the
      peripheral antinociceptive effect of diclofenac. Combinations of nonsteroidal
      anti-inflammatory drugs (NSAIDs) with other different drugs are currently used in
      clinical practice to increase the analgesic efficacy and to reduce adverse
      events. We evaluated the effect of the combination of diclofenac and the
      activator of K+ channels pinacidil in the formalin test. Female Wistar rats (180
      200 g) were injected in the dorsal surface of the right hind paw with 50 microl
      of formalin (1%). Nociception was quantified as the number of flinches of the
      injected paw during the next 60 mins, while reduction of flinches was considered
      antinociception. Ipsilateral, but not contralateral, pretreatment with diclofenac
      (25-200 microg/paw) or pinacidil (5-50 microg/paw) significantly reduced, in a
      dose-dependent manner the formalin-induced flinching behavior during the second
      phase of the test. To determine if pinacidil was able to increase the effect of
      diclofenac, noneffective increasing doses of pinacidil were coadministered with
      an ineffective dose of diclofenac (25 microg). The local co-administration of
      pinacidil and diclofenac produced a significant reduction in the number of
      flinches during phase 2, but not during phase 1 of the test compared to the
      effect of either drug alone. In conclusion, the combination of individually
      ineffective doses of diclofenac and pinacidil produce an antinociceptive effect
      in the formalin test. In addition, pinacidil increased the action of diclofenac,
      probably through the activation of K+ channels.

PMID- 16416662
TI  - Acute interactive effects of estradiol and benzodiazepines on the central nervous
      system.

PMID- 16416664
TI  - Effects of mesocaval shunt on the pharmacokinetics of metronidazole in young
      rats.
AB  - Prophylactic and therapeutic management of portosystemic encephalopathies is
      based on protein restriction in the diet, and the use of lactulose and
      antibiotics such as metronidazole. These actions intend to reduce the main source
      of intestinal ammonia production and release into the systemic circulation. The
      aim of this study was to evaluate the medium-term effects of mesocaval shunt on
      the pharmacokinetics of metronidazole in rats with healthy livers. Male Lewis
      rats were divided into two groups. The first group was subjected to mesocaval
      shunt (MCS) and the other employed as a control. The following tests were carried
      out in both groups: metronidazole pharmacokinetics, determination of ALT, AST,
      albumin, urea and ammonium, liver weight and histomorphology. A loss in body and
      liver weight was registered in rats subjected to MCS. AST levels also increased
      compared to controls. Significant differences in almost all pharmacokinetic
      parameters were detected between MCS and control rats, especially in Kel, AUC and
      Cmax. Modifications in metronidazole pharmacokinetics and liver weight changes
      without microstructural modification secondary to MCS were found. We suggest that
      individual drug-monitoring and pharmacokinetic analysis must be carried out in
      metronidazole medicated patients with modifications in portal circulation with or
      with out macro or micro liver structural alterations.

PMID- 16416663
TI  - Analgesic efficacy of tramadol by route of administration in a clinical model of
      pain.
AB  - The objective of this study was to evaluate the analgesic efficacy produced by
      tramadol given by two different routes of administration in patients experiencing
      pain after removal of an impacted mandibular third molar under local anesthesia.
      A double-blind, randomized, placebo-controlled clinical trial was conducted.
      Patients were assigned into four groups of treatment, twelve subjects per group:
      Group A, tramadol 50 mg IM one hr before surgery; group B, tramadol 50 mg into
      the surgical site; group C, tramadol by both routes of administration, 50 mg IM
      one hr before surgery plus 50 mg into the surgical site; and group D, control. We
      evaluated intensity of pain and analgesic consumption as was requested.
      Demographic characteristics and variables describing the difficulty of the
      surgical procedure were similar between groups. The duration of the anesthetic
      effect was significantly longer in the groups where tramadol was injected into
      the surgical site (215 and 252 min). Administration of systemic and local
      tramadol (50 mg) suppressed the pain intensity values in comparison to the
      control group (p < 0.05). Also, tramadol in both routes of administration
      suppressed the pain intensity values in comparison to all groups (p < 0.05). A
      significant reduction in the consumption of ketorolac was seen in all treatments
      as compared to the control group. However, only in the route combination group
      was a significant reduction in the requirement of acetaminophen observed. Nine
      patients requiring additional medication were treated with ketorolac 30 mg
      injected intramuscularly; 2 in the systemic group, 2 in the local group, 4 in the
      control group and only 1 in the combination group. Adverse events were minimal
      and similar in all groups.

PMID- 16416665
TI  - Antinociceptive effect of selected Mexican traditional medicinal species.
AB  - Pain is considered one of the most common complaints worldwide for which patients
      seek treatment. Conventional analgesic agents have played an important role in
      modern pain therapy, but they cause several adverse effects. Therefore, the
      search for new and better analgesics agents continues. The present study was
      designed to investigate the antinociceptive potential of six Mexican medicinal
      herbs commonly employed for the treatment of anti-inflammatory diseases and pain.
      The antinociceptive effect was tested in male mice using the writhing test. In
      this test intraperitoneal administration of acetic acid (0.6%) provokes abdominal
      contractions, movements of the body as a whole (particularly of the hind paws),
      twisting of dorsoabdominal muscles, and reduction in motor activity. Reduction of
      stretching per unit of time was considered as antinociception. Methanol
      chloroform extract of the plants Exostema caribaeum, Brickellia veronicaefolia,
      Scaphyglottis livida, Ligusticum porteri, Gnaphalium spp, and Amphipterygium
      adstringens were prepared by maceration. After eliminating the solvent in vacuo,
      the extracts were administered orally and the antinociceptive activity
      determined. The results indicated that the extracts of Exostema caribaeum,
      Gnaphalium spp, and Amphipterygium adstringens did not produce an antinociceptive
      effect. However, those of Brickellia veronicaefolia, Scaphyglottis livida and
      Ligusticum porteri produced a significant reduction in the number of stretches in
      the acetic acid-induced writhing test.

PMID- 16416666
TI  - Pontine norepinephrine content after motor cortical ablation in rats.
AB  - It has been reported that norepinephrine (NE) plays an important role in recovery
      after brain damage. However, the role of the pons, the site where the
      norepinephrinergic locus coeruleus (LC) is located, has not been elucidated. In
      order to study the changes in the pontine NE content in either noninjured,
      injured or recovered rats, we used 35 animals trained to walk across to a walkway
      where their footprints were recorded. Subsequently, 17 trained rats were sham
      operated while 18 were injured by means of an ablation of the right motor cortex
      representative of the hindlimb. From the injured rats, 6 were sacrificed 6 hr
      before surgery in order to obtain the pons, while all the remaining rats were
      recorded in the walkway 6, 24 and 48 hr post-surgery. Then, rats were sacrificed
      by decapitation, the pons was removed and each hemisphere was prepared for the
      chromatographic analysis of NE. Results showed that after cortical brain damage,
      the length of the stride decreased while the angle of the stride increased 6 hr
      post-surgery. Recovery was observed after 24 hr. NE increased in the pons after 6
      hr and returned to normal levels when rats had recovered. This suggests that
      cortical damage elicits NE changes in the LC that could reorganize the system to
      lead the recovery process. Such findings must be taken in account when
      pharmacotherapy with antidepressants or antipsychotics that act on norepinephrine
      containing neuronal systems are prescribed in patients after stroke.

PMID- 16416667
TI  - Plant products with anti-cancer properties employed in the treatment of bowel
      cancer: literature review 1985 and 2004.
AB  - The use of extracts of plant origin for the treatment of cancer has seen renewed
      interest. In Mexico, "Herbalists" have practiced since before Spanish times, but
      now at Mexican medical schools the alternative medicines are not taught. The aim
      of this work was to carry out a review of the international literature to
      identify and analyze the use of articles in the treatment of cancer with
      principles of plant origin. An online review was conducted of citations published
      between 1985 and 2004, selecting those works in which plant products demonstrated
      pharmacological activity useful against cancer with particular reference to bowel
      carcinoma. In 45 articles, we looked for common and scientific names, part of
      plant and/or its products used as treatment or preventive, used in an
      experimental in vivo or in vitro model, pharmacological effects and actions,
      human or animal species studied and apparent efficacy. Fifty-five percent used
      human cancer cell lines as a model, incubated with plant extracts; 40% used
      animal species to induce tumors and protect them with plant extracts; only 5%
      were clinical studies. Additionally, we determined which of these natural
      products are included in relevant references: two are marketed in Mexico; none
      were listed in the academic Mexican book "Vademecum Academico de Medicamentos";
      one was found in Goodman Gilman's The Pharmacologic Basis of Therapeutics, while
      three were listed in Katzung's Medical Pharmacology. Experimental data support
      the empirical use of natural plant products against cancer by their
      chemopreventive effects, but they are not considered drugs. Despite not being
      listed as drugs, these remedies should be covered in pharmacology courses when
      evidence of mechanisms of action is available. Our review suggests that medical
      schools should review "traditional medicines" in order that graduates know what
      treatments patients are using and those that may be of value.

PMID- 16416668
TI  - Effect of age on the pharmacokinetics of ranitidine in healthy Mexican
      volunteers.
AB  - Numerous reports in the literature have demonstrated changes in drug
      pharmacokinetics that result with age. Ranitidine is a drug commonly used in
      Mexico. However no reports on the pharmacokinetics of ranitidine in the Mexican
      population are available in the literature. The objective of this clinical trial
      was to evaluate the effect of age on the pharmacokinetics of ranitidine in
      healthy Mexican volunteers. METHODS: Twenty-one healthy Mexican volunteers were
      included, who were divided into three groups G1 (18-30 y), G2 (31-50 y) and G3
      (51-60 y). The volunteers were given a single oral dose of 300 mg of ranitidine
      and blood samples were obtained, and some pharmacokinetic parameters were
      correlated with age. RESULTS: Statistically significant differences were noted in
      the distribution volume (4.00 +/- 1.11 L/kg in G1, vs 2.15 +/- 1.12 L/kg in G3)
      of the drug. Clearance was faster among the G1 (1.11 +/- 0.12 mL/hr) group
      compared to the G3 group (0.58 +/- 0.19 mL/hr). Differences for AUC, t1/2 and
      Cmax are more evident between G1 and G3. DISCUSSION: The results of our study
      indicated that in patients over 50 years of age who are treated with ranitidine,
      the dosage of this agent should be appropriately adjusted in order to avoid
      adverse effects that may develop with prolonged use of the drug. However it is
      very important to consider that our result only reflect observations made from a
      single dose study, thus it is necessary to carry out study under chronic dosage
      treatment.

PMID- 16416669
TI  - Chronic exposure to arsenic sensitizes CD3+ and CD56+ human cells to sodium
      arsenite-mediated apoptosis.
AB  - Despite the relevance of immune responses in cancer development, little is known
      about arsenite-induced apoptosis on different immune effectors cells. In this
      work, we determined the effect of in vitro exposure to sodium arsenite on
      apoptosis rates of blood lymphocytes, monocytes and NK cells. Blood was obtained
      from six healthy non-exposed donors, and also from a woman chronically exposed to
      arsenic. The results indicated that in vitro exposure of mononuclear cells (MNC)
      from non-exposed donors to sodium arsenite showed no increase in apoptosis as
      compared to non-treated cells. In contrast, cells obtained from the exposed-donor
      showed a significant increase in apoptosis after the treatment with sodium
      arsenite as compared to non-treated cells. This effect was observed in CD3+ and
      CD56+ but not in CD14+ cells. In addition, we found a preexisting high basal
      level of apoptosis in MNC from the exposed-donor. These results indicate that
      chronic exposure to arsenic increases the sensitivity of immune cells to in vitro
      sodium arsenite-mediated apoptosis.

PMID- 16416670
TI  - Effect of oral chronic intoxication with sodium arsenite on murine giardiasis.
AB  - Chronic exposure to toxicants alters immune function that can affect the ability
      of the host to mount a response to infection. Giardiasis is a gastrointestinal
      disease in which subtle alteration in immunity of the host can transform the
      normal acute infection into a chronic one. In this work we used a murine
      giardiasis model to evaluate the effect of chronic oral intoxication with sodium
      arsenite on the characteristics of giardiasis. BALB/c mice were intoxicated
      during 45 days with water containing 50, 125 or 250 microg/mL sodium arsenite.
      Each group was then inoculated with G. muris cysts. Cysts excreted in the feces
      were isolated and quantified. The toxic effect of arsenic on intestinal
      trophozoites was evaluated using G. lamblia trophozoites cultured in vitro with
      different arsenic concentrations, corresponding to equivalent concentrations of
      arsenic found in the gut lumen of intoxicated mice. Mice intoxicated with 125 and
      250 microg/mL of sodium arsenite and infected with G. muris cysts displayed a
      shorter period of cysts excretion and were resistant to secondary infection with
      the parasite. In vitro studies showed that G. lamblia trophozoites were able to
      grow in presence of high sodium arsenite concentrations, suggesting the absence
      of a direct toxic effect on the parasite in the gut. Since a longer period of
      Giardia cysts excretion is associated with suppression of the immune system, the
      earlier clearance of primary G. muris infection in intoxicated mice suggests the
      induction of an immune modification that leads to an improved ability of mice to
      overcome the infection.

PMID- 16416671
TI  - A pilot study of pharmacokinetics of ethanol after oral administration to healthy
      Mexican volunteers.

PMID- 16416672
TI  - Phenotypical expression of CYP2D6 in amerindians of tepehuano origin from
      Durango, Mexico.
AB  - Cytochrome P4502D6 (CYP2D6) shows genetic polymorphism, which is clinically
      important in the metabolism of drugs and other xenobiotics. Dextrometorphan (DM)
      has been used as a test compound to evaluate the in vivo activity of CYP2D6.
      Phenotypical frequencies of CYP2D6 have been determined in some populations, but
      little is known about them in native populations. The object of this study was to
      characterize the phenotypical expression of CYP2D6 in Amerindian subjects of
      Tepehuano origin from the State of Durango, using DM as metabolic marker, as well
      as the effect of age, sex and nutritional status on this activity. Three hr after
      oral administration of a single 30 mg dose of DM, the plasma concentration of DM
      and its metabolite dextrophan (DX) were determined with HPLC in 55 Tepehuano
      subjects. All subjects were extensive metabolizers (metabolic ratio MR < 0.3). No
      correlation of age, sex or nutritional status was found with the DM/DX metabolic
      ratio. However, we found a monoexponential relationship between the metabolic
      ratio of DM and DX, and their concentrations respectively, which can have
      clinical applications, since metabolic ratio can be predicted from a known DM or
      DX concentration. Three hr after ingestion of DM, 18 individuals showed DM plasma
      concentrations of 5 to 10 ng/mL, 15 subjects of 11 to 20 ng/mL, 8 subjects of 21
      to 50 ng/mL and 14 subjects >51 ng/mL pointing out that DM concentrations and MR
      must be determined to establish toxicity risk levels.

PMID- 16416673
TI  - Metabolism of omeprazole after two oral doses in children 1 to 9 months old.
AB  - Proton pump inhibitors (PPIs) have been used recently for gastrointestinal
      esophageal reflux disease (GERD) in children older than one year with good
      results. However, the pharmacokinetics of PPIs have not been studied in children
      less than two years old. The aim of our study was to evaluate the frequency of
      the main phenotypes of the metabolizing enzymes CYP2C19 and CYP3A4 in Mexican
      infants. Our results indicate no significant difference between the 0.5 and the
      1.5 mg/kg doses. The percentage of CYP2C19-poor metabolizers was 17% in babies
      below 4 months and was not detected in children above 3 months. When a combined
      CYP2C19- and CYP3A4- phenotype was estimated, omeprazole levels were
      significantly higher in poor metabolizers than in extended metabolizers. The
      percentage of ultra-extensive metabolizers in children older than 3 months were
      20% and 33% for CYP2C19 and CYP3A4 respectively, compared to only 6% and 9%
      respectively, in babies between 1 and 3 months old. In general children, under 4
      months had higher omeprazole levels and an immature metabolism. Studies in
      children older than 2 years old have showed similar pharmacokinetics to adults.
      For children between 1 month old and up to 9 months, we suggest the use of the
      0.5 mg/kg dose, since it prevents accumulation in poor metabolizers, caution is
      recommended to identify ultra-fast metabolizers, but this would require new
      studies.

PMID- 16416674
TI  - c-Abl is required for staurosporine-induced caspase activity.
AB  - Caspases are the intracellular molecular machinery responsible for apoptotic cell
      death. The regulation of these critical proteolytic enzymes is known to occur on
      multiple levels. While their expression as inactive precursors exhibits a primary
      level of control, other types of regulation such as post-translational
      modifications also play a role. Nuclear c-Abl, a nonreceptor tyrosine kinase,
      plays a role in the regulation of apoptosis in response to DNA damage. The
      function of cytoplasmic c-Abl in cell death is not fully understood. Here, we
      report c-Abl dependent caspase-3 and caspase-8 activity in response to
      staurosporine. Despite the presence and apparent activation of the mitochondrial
      dependent apoptotic pathway and cellular demise, we find no caspase-3 activity in
      cells lacking the Abl gene (Abl(-/-)). These findings demonstrate a novel
      tyrosine kinase dependent regulation of caspase-mediated cell death.

PMID- 16416675
TI  - Effect of nutritional status and ozone exposure on Na+/K+ ATPpase and lipid
      peroxidation in rat brain.
AB  - The aim of this study was to analyze the effect of nutritional status and
      exposure to ozone on the activity of Na+/K+ ATPase and lipid peroxidation in rat
      brain. Male Wistar rats were fed 7% and 23% protein diets. Two groups were formed
      for each nutritional status: one group was exposed for 15 successive days to 0.75
      ppm of ozone in air and the other was exposed to air. Subsequently, the brain was
      dissected and cortex, hemispheres, cerebellum and brainstem separately
      homogenized to measure the activity of thiobarbituric acid reactive substances
      (TBARS) and ATPase in the presence and absence of ouabain. The activity of Na+/K+
      ATPase increased in cerebellum of well-nourished rats exposed to ozone, while
      total ATPase and TBARS decreased in all studied areas in the malnourished groups.
      These results suggest that nutritional status and exposure to ozone generate
      changes in lipid membrane composition, in turn changing the activity of sodium
      pump with similar consequences for brain metabolism.

PMID- 16416676
TI  - Bromocriptine induces regression of left ventricular hypertrophy in peritoneal
      dialysis patients.
AB  - Left ventricular hypertrophy (LVH) prevalence is very high in end stage renal
      disease (ESRD). It's a predictor of cardiac death in peritoneal dialysis
      patients. Noradrenalin, Angiotensin II and aldosterone are involved incardiac
      hypertrophy. Dopamine, acting at DA2 receptors inhibits norephinephrin release,
      antagonizes aldosterone and down-regulates AT1 receptor numbers, suggesting that
      DA2 agonists, like bromocriptine (BEC) could regress LVH. The objective of this
      study was to evaluate the changes in left ventricular mass in patients with ESRD
      in continuous ambulatory peritoneal dialysis (CAPD), by adding BEC to the
      treatment. An open clinical trial was conducted. Twenty patients were enrolled.
      Five formed the control group. Fifteen patients in the experimental group
      received BEC 2.5 mg three times daily over three months. M mode echocardiography
      and prolactin plasma levels were measured at the beginning and at the end of the
      study. The statistical analysis was performed using Student t test. The
      echocardiography reports showed a 24.4% decreased in left ventricular mass index
      (LVMI); the interventricular septum decreased 11.3%, the ejection fraction was
      not modified. The control group showed no difference. BEC-mediated decreases in
      left-ventricular mass in LVH patients on dialysis suggest that Dopaminergic
      agonists could be useful in caring for patients with ESRD and LVH.

PMID- 16416677
TI  - Cholesterol depletion enhances both spontaneous and agonist-evoked uterine smooth
      muscle contractions in a reversible manner.
AB  - In experiments designed to determine the consequence of cholesterol depletion on
      relaxation signaling in the uterus, we treated isolated strips of guinea pig
      myometrium in organ baths with beta-methyl cyclodextrin (beta-MeCD) to remove
      cholesterol expecting suppression of spontaneous activity and uncoupling of
      agonist specific relaxation as we have shown in vascular muscle (Circulation
      Research 91:292-299, 2002). Treatment of myometrium with 15 mM beta-MeCD for 15
      min led to enhancement of spontaneous activity that was further increased
      following a second beta-MeCD treatment. beta-MeCD treated tissues developed
      increased force on top of that already present basally when stimulated by OT, but
      reached the same maximum as control tissues. Washout of OT relaxed control but
      not beta-MeCD pretreated tissues. When cholesterol depleted tissues were repleted
      with cholesterol using a water-soluble preparation, they immediately relaxed to
      baseline. Overloading of cholesterol to beta-MeCD-naive tissues suppressed
      spontaneous contractions and diminished responses to OT. These findings suggest
      that cholesterol selectively uncouples relaxation signaling. We propose that
      myometrial activity may be altered in women acutely by changes in serum
      cholesterol and that understanding the distinctions between myometrial smooth
      muscle and other smooth muscles may reveal heretofore unknown therapeutic targets
      for the treatment of uterine dysfunction.

PMID- 16416678
TI  - Effects of single administration of diethylstilbestrol on murine langerhans
      cells.
AB  - Diethylstilbestrol (DES) is a synthetic compound with potent estrogenic actions
      useful in the treatment of prostate carcinoma despite the fact that it can also
      induce some forms of neoplasia. Both effects are thought to be related to its
      estrogenic actions and very little attention has been focused on the possible
      effect of DES on the immune response. Skin is the largest organ of the body and
      constitutes the first line of defense against xenobiotics. The Skin Immune System
      (SIS) has become the center of attention of research for the development of new
      therapeutic approaches for neoplasic diseases. Langerhans cells (LC), as an
      element of SIS, are "professional" antigen presenting cells resident in the skin
      that participate in the immune response associated with tolerance and acquired
      immunity to antigens. Hence in this work we studied the effect of DES on LC of
      murine skin as a model to analyze the possible effect of DES on the immune
      response. Male CD-1 mice (20 to 35 g body weight) were treated topically (TO) or
      subcutaneously (SC) with DES (10 and 100 mg/kg, dissolved in ethanol) and
      sacrificed at 12, 84 and 228 hr. LC were quantified in the ear skin of mice using
      both an enzymatic histochemical technique to demonstrate ATP-ase activity; and an
      indirect immunohistochemical assay for detecting class II molecules of the major
      histocompatibility complex (MHC-II). DES induced a significant time- and dose-
      dependent reduction in the number of LC (P < 0.05). Data presented here suggest
      that estrogens may exert a modulatory action on LC.

PMID- 16416679
TI  - Nephropathy in critically Ill patients without preexisting renal disease.
AB  - Contrast-induced nephropathy (CIN) remains a common complication of radiographic
      procedures. Isovue (lopamidol) is a low-osmolality nonionic monomeric tri
      iodinated water soluble agent widely used as a contrast medium in radiographic
      procedures for intravascular, intrathecal, and body cavity administration. The
      purpose of this study was to evaluate the effect of lopamidol on renal function
      in patients without any preexisting renal condition who were undergoing
      radiographic imaging with the iodine contrast. Seventy-five patients admitted to
      the Intensive Care Unit (ICU) had CT-scans with intravenous lopamidol contrast.
      All the patients had a normal serum creatinine before administration of the
      contrast media. Serum creatinine was recorded for three consecutive days after
      the CT-scan. The control group consisted of medical ICU patients that were not
      administered iodine contrast during their stay in the unit. There was no change
      from the baseline in the control group. A significant increase in serum
      creatinine was recorded in patients undergoing CT-scan with lopamidol contrast.
      In 18% of the patients, creatinine was elevated more than 25% from the baseline.
      This level of creatinine elevation indicated a significant decrease in glomerular
      filtration, and thus fulfilled the criteria for contrast-induced nephropathy. Our
      data demonstrates that iodine contrast media for CT in ICU patients without
      preexisting kidney disease can precipitate clearly measurable nephropathic
      changes.

PMID- 16416680
TI  - Correlation between cardiac enzyme elevation and the duration of cardiopulmonary
      resuscitation.
AB  - Cardiovascular disease is the leading cause of death in the United States. Acute
      myocardial infarction (MI) is defined as necrosis of myocardial cells. Several
      studies have shown that cardiac markers are elevated after successful
      cardiopulmonary resuscitation (CPR) due to physical as well as electrical trauma.
      Correlation has never been established between an elevation in cardiac markers
      and patient age, the amount of trauma induced during resuscitation, or the
      duration of chest compression. Previous studies have determined that cardiac
      troponin (cTnl) is the most sensitive marker in cardiac injury. In this study, we
      hypothesized that the duration of CPR and the patient's age had a direct
      correlation with cardiac injury demonstrated as an elevation of cTnl. We analyzed
      retrospectively 81 patients that underwent successful CPR in an in-hospital
      setting. 13 patients were excluded from the analysis due to positive cTnl prior
      to cardiac arrest. Duration of CPR, as well as cTnl levels before and after
      cardiac arrest were recorded and analyzed in the remaining 68 patients. Patients
      with a negative cTnl after successful CPR (n=30) were stratified into Group A.
      The remaining patients (Group B) had a positive cTnl ranging from 2.2-31 ng/ml.
      The mean age and the mean duration of CPR in minutes were calculated and compared
      using t-Test analysis. There was no statistical difference in age between Group A
      and Group B. Patients in Group A had a mean CPR duration of 12.2 minutes, while
      patients in Group B had a mean CPR duration of 19.8 minutes (p < 0.02). We found
      that the duration of cardiopulmonary resuscitation was positively associated with
      the elevation of cardiac markers.

PMID- 16416681
TI  - Etiology of cerebrovascular accidents in octogenarians.
AB  - Stroke is the third leading cause of death in the United States, after coronary
      heart disease and cancer. Many survivors are left with mental and physical
      impairment and require assistance with activities of daily living. Twenty-eight
      percent of patients with stroke are under 65 years of age. We analyzed
      retrospectively 213 elderly patients with the diagnosis of ischemic
      cerebrovascular event that were consecutively admitted to the stroke unit of our
      institution between January 2002 and December 2004. Patient age varied from 65 to
      100 years (mean = 79.8 years), and there were 66.19% females and 33.81% males. We
      analyzed the head CT findings of all the patients and separated the patients into
      two groups based on the results. Patients in Group I had large infarcts on CT and
      extensive neurological deficits, while patients in Group II had small lacunar
      infarcts and minor neurological findings. The charts of all the patients were
      reviewed retrospectively and data on hypertension, diabetes mellitus, carotid
      stenosis, atrial fibrillation, left ventricular hypertrophy and anticoagulation
      were retrieved and analyzed. Our results showed that 35.6% (76) of the patients
      suffered a major stroke (Group 1) and the remainder 64.4% (137) suffered small
      lacunar strokes (Group 2). More than half (57.9%) of the patients in Group I were
      found to have atrial fibrillation and significant carotid stenosis (35.5%) and
      22.4%), respectively. The remaining patients (28) were hypertensive and 12% had
      diabetes mellitus, but no extracerebral source of embolism was found. In Group
      II, only 13.1% were found to have atrial fibrillation or significant carotid
      stenosis, but all were hypertensive and 86% suffered from diabetes. Our results
      indicate that major strokes are less prevalent in the geriatric population than
      small lacunar strokes and tend to be more related to hypertension and diabetes.

PMID- 16416682
TI  - Troponin I as a marker of doxorubicin induced cardiotoxicity.
AB  - Doxorubicin is a chemotherapeutic agent successfully used in the treatment of a
      wide range of cancers. However, with cumulative doses, doxorubicin also is known
      to have cardiotoxic effects, including cardiomyopathy and heart failure.
      Identification and quantification of myocardial cell damage has been a point of
      Controversy. We sought to identify these changes by measuring the levels of
      troponin I both 24 and 48 hr after the administration of doxorubicin as part of
      an antineoplastic treatment regimen. Thirty-eight patients scheduled to undergo
      treatment with doxorubicin were screened and approached for enrollment in the
      study. Thirty-one of them fulfilled all the inclusion criteria and also signed
      informed consent. All the patients enrolled in the study had blood drawn before
      the administration of doxorubicin and also 24 and 48 hr later. Electrocardiograms
      were performed prior to and 48 hr following the administration of chemotherapy.
      The dose of doxorubicin administered was calculated by the oncologist and ranged
      from 450 mg/m2-650 mg/m2 (mean 520 mg/m2). Only one patient was found to have en
      elevation of troponin levels both 24 and 48 hr (2.3 ng/mL and 2.1 ng/mL,
      respectively) after the administration of the drug. During that time, the patient
      denied any chest pain, shortness of breath or palpitations. Repeat ECG did not
      show any changes from the baseline. The remaining participants continued to
      maintain a troponin level of less than 0.3 ng/mL during the follow-up. In these
      patients, no electrocardiographic changes were noted in the follow-up ECG
      compared to the baseline; however, a slight drop in the ejection fraction without
      any impact on the clinical presentation was recorded. We concluded that the cTnl
      level does not change after the administration of doxorubicin, and thus cannot be
      used as a predictor of doxorubicin-induced cardiotoxicity.

PMID- 16416683
TI  - Unique case of thrombotic thrombocytopenic purpura and diabetes insipidus.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare and often fatal disorder
      characterized by thrombocytopenia, microangiopathic hemolytic anemia, mental
      status changes, and renal dysfunction. Central diabetes insipidus (CDI) is a rare
      disease due to anatomic lesions of the hypothalamicpituitary system associated
      with various underlying diseases, or trauma. We present an unusual case of TTP
      and CDI in a 47 year-old African American female who was admitted to our hospital
      with crampy abdominal pain and nausea. The patient had tachycardia, fever and
      hypotension. The patient subsequently became confused, developed seizures, and
      her renal function deteriorated. Bone marrow analysis showed adequate
      megakaryocytes while a peripheral smear revealed severe thrombocytopenia,
      polychromasia and schistocytes. The diagnosis of thrombotic thrombocytopenic
      purpura (TTP) was made and plasmapharesis initiated. Over the next few days, the
      patient developed severe polyuria with a rise in serum sodium. Central diabetes
      insipidus was diagnosed and DDAVP (desmopressin acetate, 1-deamino-8-D-arginine
      vasopressin) was given. However, DDAVP was stopped several times due to worsening
      thrombocytopenia. Renal function worsened and the patient expired. A review of
      the literature revealed only one case of report of TTP and central diabetes
      insipidus. Our case was the only one reporting the use of DDAVP in such a
      setting.

PMID- 16416684
TI  - Prolonged requirement for ventilatory support in a patient with Eskalith
      overdose.
AB  - Lithium (Eskalith) is commonly used in the treatment of depressive and bipolar
      affective disorders, in a population at relatively high risk for overdose.
      Lithium may help correct a chemical imbalance in the brain; however, it has a
      comparatively narrow therapeutic index. Thus, lithium intoxication is a frequent
      complication of chronic lithium therapy. The central nervous system (CNS) is the
      major organ system affected, although the renal, gastrointestinal (GI),
      endocrine, and cardiovascular (CV) systems also may be involved. Here we present
      a forty-two-year-old Caucasian female with altered mental status, inability to
      eat, speak or walk properly, with shaking and vomiting for three days. Past
      medical history was significant for hepatitis C and bipolar disorder. Vital signs
      were within normal limits. Physical exam revealed a patient with aphasia, tremor,
      and an expressionless face, able to make eye contact and move all four
      extremities. However, she was unable to follow commands and she expressed
      rigidity of extremities, mild tachycardia, and stupor. Severely elevated serum
      lithium levels were found. A diagnosis of severe lithium toxicity was made and
      the patient was admitted to the telemetry unit. Intravenous hydration with normal
      saline was initiated as the patient had normal kidney function, and urinary
      output was monitored. All psychotropic medications were held except for a
      benzodiazepine. In the meantime the patient developed acute respiratory distress,
      was intubated on clinical grounds and was transferred to the intensive care unit.
      Acute cardiogenic pulmonary edema and other causes of respiratory distress were
      ruled out; diagnosis of Adult Respiratory Distress Syndrome (ARDS) was made.
      After two months of mechanical ventilation, the patient was stabilized. Mental
      status, vital signs, and all laboratory parameters including thyroid function
      tests, normalized. The patient was transferred to a rehabilitation center. This
      is a rare case of ARDS associated with lithium intoxication.

PMID- 16416685
TI  - Detection of cytotoxic activity of Psacalium palladium on normal mouse spleen
      cells and transformed human cells.
AB  - A decoction from roots and rhizomes of Psacalium palladium is used in Mexico for
      the treatment of tumors and for control of diabetes mellitus, among other
      ailments. Although hypoglycemic activity has been demonstrated in various
      experimental models and some compounds have been detected in the roots and
      rhizomes, such as alkaloids, glycosides and tannins, toxicity studies have not
      yet been performed. Moreover, since various species taxonomically related to P.
      palladium have pyrrolizidine alkaloids (hepatotoxic, carcinogenic and mutagenic
      agents) it is possible that these species also contain potentially toxic
      substances, which represents a risk for users. The aim of this investigation was
      study the cytotoxicity of P. palladium on mouse hematopoietic cells and
      transformed human cells, evaluating the cell proliferation by the technique of
      sulforhodamine B. An aqueous fraction (AS) reduced population of both types of
      cells by over 50%; meanwhile the other extracts did not alter cell number.
      Fraction AP was cytotoxic for DU-145 cells at 10 microg/mL, whereas the remaining
      extracts acted like cytostatic agents.

PMID- 16416686
TI  - Cervical cancer screening among elderly urban women in a primary care setting.
AB  - Cervical cancer remains an important cause of morbidity and mortality in older
      women. The cancer screening by means of Papanicolaou (Pap) smear testing has been
      shown to improve early detection. One quarter of new cases of invasive cervical
      cancer occur in women age 65 and older, yet only 52% of this population has had
      cervical cytology within the past 3 years, and approximately 25% of elderly women
      have never been screened. Other populations found to be at risk for
      underutilization of screening include the uninsured, the poor, and ethnic
      minorities, especially Hispanics and elderly Blacks. In this study, we examined
      the prevalence of abnormal Pap smears in various primary care settings in the New
      York City borough of Queens. The majority of abnormal Pap smears were found in
      the 65-70 year age group. This group also had the most advanced lesions. The 76
      80 year age group had the lowest rate: 13.4 per 1000. The highest abnormal Pap
      smear rate was in the >86 year age group: 85.7 per 1000. However, none were high
      grade lesions. Overall, the rate of abnormal Pap smears was 31.5/1000 for all
      patients > age 65. This study of Pap smears in a multi-ethnic sample of elderly
      urban women found the prevalence of abnormal smears to be higher than in prior
      studies. The ramifications of this may be that Pap smear screening should
      continue beyond the age of 65, especially if the patient has not had negative
      screening results in the past. In addition, the alarming rate of abnormal Pap
      smears in the Black and "Other" populations in this study reinforces the need for
      culturally appropriate health screening measures for these patients.

PMID- 16416687
TI  - Selection of information resources for education in medical pharmacology.
AB  - Pharmacology is the foundation science of medical pharmacotherapy. Education in
      medical pharmacology (EP) requires the use of information resources (IR) to meet
      the challenge of the continuous introduction of new drugs and new educational,
      didactic and pedagogical theories to enhance knowledge. Hence criteria for
      selecting bibliographic material for EP should be clearly outlined and
      implemented. In this work we present a method to select IR for EP based on
      systems theory and focusing on the factors determining: (a) the integration of a
      list of recommended IR for EP; (b) the design of the acquisition list for faculty
      and students work; (c) the overall organization of the resources available for
      its optimal use and benefit in the educational process; and (d) a general
      strategy for assessing the impact of the bibliographic infrastructure. The
      proposal is based on information from: (i) lists of recommended readings in the
      academic program of the Pharmacology course given at the School of Medicine of
      UNAM in the last 30 years; (ii) the extent of discipline development measured by
      two indexes derived from the contents of Goodman and Gilman's "Pharmacological
      Basis of Therapeutics" (G & G); (iii) the number of texts currently found in the
      collection of FM-UNAM which are classified in the section of Pharmacology using
      the Library of Congress Classification System (LCCS); and (iv) the comparison of
      academic versus standardized classification of pharmacology topics, such as
      Medical Subject Heading (MESH) and LCCS The importance of this proposal relates
      to its usefulness for EP and for other medical disciplines.

PMID- 16416688
TI  - The diagnosis and management of sinusitis: a practice parameter update.

PMID- 16416689
TI  - Demonstrating excellence in practice-based research for public health.
AB  - This document explores the opportunity for scholarship to enhance the evidence
      base for academic public health practice and practice-based research.
      Demonstrating Excellence in Practice-Based Research for Public Health defines
      practice-based research; describes its various approaches, models, and methods;
      explores ways to overcome its challenges; and recommends actions for its
      stakeholders in both academic and practice communities. It is hoped that this
      document will lead to new partnership opportunities between public health
      researchers and public health practitioners to strengthen the infrastructure of
      public health and add new dimensions to the science of public health practice.
      Demonstrating Excellence in Practice-Based Research for Public Health is intended
      for those who produce, participate in, and use practice-based research. This
      includes academic researchers and educators, public health administrators and
      field staff, clinical health professionals, community-based organizations and
      professionals, and interested members of the public.

PMID- 16416690
TI  - Bioterrorism preparedness.

PMID- 16416691
TI  - Depression and hip fracture.

PMID- 16416692
TI  - Pregnancy Risk Assessment Monitoring System (PRAMS): possible new roles for a
      national MCH data system.
AB  - The Pregnancy Risk Assessment Monitoring System (PRAMS) was established by the
      Centers for Disease Control and Prevention (CDC) in 1987 in five states, and
      today 32 states participate. Using states' vital statistics (birth certificates)
      as its population-based sampling frame, PRAMS "follows back" a stratified sample
      of women several months post-partum, surveying them about their own and their
      infant's prenatal, birth, and post-partum behavior and experiences. It uses a
      standardized protocol and multiple data collection modalities. PRAMS was
      initiated in an era of intense state and national interest in infant mortality,
      racial disparities reduction, and publicly supported prenatal care program
      expansion-and a lack of state-specific information available to inform local and
      state program development and assessment. The PRAMS format allows more in-depth
      inquiry about reproductive health topics than is possible from the more
      widespread but limited set of information available on birth certificates. PRAMS
      carries on a long, proud tradition of follow-back studies in the maternal and
      child health (MCH) field. In the 1920s, the U.S. Children's Bureau conducted the
      nation's first major in-depth study on infant mortality using a similar follow
      back methodology. In each of 10 cities, every woman whose infant had died in the
      past year was systematically surveyed. The results provided an initial
      understanding of the nature of infant mortality in the U.S., indicating that
      infant deaths occurred more often in lower-income than higher-income families,
      among bottle-fed than breast-fed infants, and among twins than singletons.
      Beginning in 1964 and every eight years thereafter through 1988, the National
      Center for Health Statistics (NCHS) conducted intensive national follow-back
      studies of live births and infant/fetal deaths, which has provided much of our
      more recent national epidemiologic information about pregnancy and births,
      especially concerning smoking, prenatal care usage, etc. A similar Department of
      Education/NCHS national follow-back and longitudinal follow-up study, the Early
      Childhood Longitudinal Study-Birth Cohort (ECLS-BC) was begun in 2001 and will
      survey 10,000 mothers and their infants through kindergarten age.

PMID- 16416693
TI  - Why choice of survey mode makes a difference.

PMID- 16416694
TI  - Measuring the public's health.
AB  - Allocation of public health resources should be based, where feasible, on
      objective assessments of health status, burden of disease, injury, and
      disability, their preventability, and related costs. In this article, we first
      analyze traditional measures of the public's health that address the burden of
      disease and disability and associated costs. Second, we discuss activities that
      are essential to protecting the public's health but whose impact is difficult to
      measure. Third, we propose general characteristics of useful measures of the
      public's health. We contend that expanding the repertoire of measures of the
      public's health is a critical step in targeting attention and resources to
      improve health, stemming mounting health care costs, and slowing declining
      quality of life that threatens the nation's future.

PMID- 16416695
TI  - Surveillance programs for chronic viral hepatitis in three health departments.
AB  - Although chronic hepatitis B and chronic hepatitis C are diseases of public
      health importance, only a few health departments nationally have chronic viral
      hepatitis under surveillance; these programs rely primarily on direct reporting
      by medical laboratories. We conducted an evaluation to determine if lessons from
      these programs can guide other health departments. Between December 2002 and
      February 2003, we visited the Connecticut Department of Public Health, the
      Multnomah County Health Department in Portland, Oregon, and the Minnesota
      Department of Health to determine the capacity of their chronic hepatitis
      registries to monitor trends and provide case management. We found that the
      registries facilitated investigations of potentially acute cases by identifying
      previously known infections, and aided prevention planning by pinpointing areas
      where viral hepatitis was being diagnosed. For chronic cases, case management
      (defined as the process of ensuring that infected individuals and their partners
      receive medical evaluation, counseling, vaccination, and referral to specialists
      for treatment when indicated) was provided for hepatitis B in Multnomah County,
      but was limited in other programs; barriers included resource constraints,
      difficulties confirming chronic infection, and privacy concerns. Finding
      innovative ways to overcome these barriers and improve case management is
      important if chronic hepatitis surveillance is to realize its full potential.

PMID- 16416696
TI  - Blackout of 2003: public health effects and emergency response.
AB  - We examined the public health effects of the Northeast blackout of August 2003
      and the emergency response to the blackout by the New York City Department of
      Health and Mental Hygiene (DOHMH). We reviewed departmental documents from the
      DOHMH Emergency Operations Center and surveyed DOHMH employees to identify
      deficiencies in the response and elicit suggestions for improvement. DOHMH
      deployed its all-hazards, scalable public health Incident Management System to
      respond to several impacts: (1) failure of multiple hospital emergency
      generators; (2) patients dependent on electrically powered equipment; (3) loss of
      electronic data input to the DOHMH syndromic surveillance system from hospital
      emergency departments; (4) potential for vaccine spoilage due to loss of
      refrigeration; (5) beach contamination with untreated sewage; (6) heat-related
      health effects and increase of foodborne disease; and (7) potential for an
      increased rodent population as a result of increased amounts of discarded
      perishables. Areas identified for improvement included communications during the
      event, DOHMH dependence on an external source of electricity, facility management
      during the response, and lack of readily available and appropriate emergency
      supplies.

PMID- 16416697
TI  - Validity of self-assessment of skin reaction after smallpox vaccination.
AB  - OBJECTIVE: Smallpox vaccinees should be evaluated for the presence of a major
      skin reaction ("take") one week after vaccination, but this could prove to be
      logistically infeasible in the context of an emergency mass-vaccination campaign.
      We validated a tool for self-evaluation of the vaccination site for presence of
      take. METHODS: We conducted a prospective, double-blinded, paired-measurement
      validation study of 174 non-naive adult vaccinees and their physician evaluators.
      Subjects provided paired, blinded, independent assessments of take 7-9 days after
      vaccination. RESULTS: Overall, vaccinees and evaluators agreed on 157 of 174
      (90.2%) take assessments. Sensitivity of the tool was 99.1%, and specificity was
      75%. The positive predictive value of self-assessment was 87.2% and the negative
      predictive value was 98%. Specificity of the tool and measures of agreement were
      significantly modified by age, education, and occupation. When adjusted for the
      expected take rate among a population including naive vaccinees, positive
      predictive value and overall agreement increased significantly. CONCLUSIONS: Self
      assessment may be a feasible option for evaluation of take in the event of mass
      smallpox vaccination. The predictive values and overall agreement of the tool are
      satisfactory, and can be expected to increase when used in a largely naive
      population.

PMID- 16416698
TI  - Socioeconomic status and breastfeeding initiation among California mothers.
AB  - Objectives. To examine multiple dimensions of socioeconomic status and
      breastfeeding among a large, random sample of ethnically diverse women. METHODS:
      This study used logistic regression analysis to examine the influence of a range
      of socioeconomic factors on the chances of ever breastfeeding among a stratified
      random sample of 10,519 women delivering live births in California for 1999
      through 2001. Measures of socioeconomic status included family income as a
      percentage of the federal poverty level, maternal education, paternal education,
      maternal occupation, and paternal occupation. RESULTS: Consistent with previous
      research, there was a marked socioeconomic gradient in breastfeeding. Women with
      higher family incomes, those who had or whose partners had higher education
      levels, and women who had or whose partners had professional or executive
      occupations were more likely than their counterparts to breastfeed. After
      adjustment for many potential confounders, maternal and paternal education
      remained positively associated with breastfeeding, while income and occupation
      were no longer significant. Compared with other racial or ethnic groups, foreign
      born Latina women were the most likely to breastfeed. CONCLUSIONS: The
      significant association of maternal and paternal education with breastfeeding,
      even after adjustment for income, occupation, and many other factors, suggests
      that social policies affecting educational attainment may be important factors in
      breastfeeding. Breastfeeding rates may be influenced by health education
      specifically or by more general levels of schooling among mothers and their
      partners. The continuing importance of racial/ethnic differences after adjustment
      for socioeconomic factors could reflect unmeasured socioeconomic effects,
      cultural differences, and/or policies in Latin American countries.

PMID- 16416699
TI  - Acculturation and diabetes among Hispanics: evidence from the 1999-2002 National
      Health and Nutrition Examination Survey.
AB  - OBJECTIVE: Hispanic individuals in the United States have a greater prevalence of
      diabetes mellitus than non-Hispanic white individuals; however, it is unclear
      whether Hispanics' risk of diabetes differs based on their level of
      acculturation. The purpose of our research was to examine acculturation among
      Hispanic Americans with respect to prevalence and control of diabetes. METHODS:
      We conducted an analysis of the National Health and Nutrition Examination Survey
      (NHANES), 1999-2002, a nationally representative sample of the
      noninstitutionalized U.S. population. We evaluated data on Hispanic adults (> or
      = 18 years of age, unweighted n=2,696), analyzing diagnosed diabetes, glycemic
      blood pressure and lipid control, and diabetes complications according to
      acculturation as measured by language and birth outside the United States.
      RESULTS: Hispanics with low acculturation were more likely to be without a
      routine place for health care, have no health insurance, and have low levels of
      education. In adjusted analyses, individuals with low acculturation, measured by
      language, were more likely to have diabetes (odds ratio [OR] 1.90, 95% confidence
      interval [CI] 1.02, 3.54). Among individuals with diagnosed diabetes, no
      significant association was yielded between acculturation and diabetes control.
      However, individuals with low language acculturation were more likely to have the
      diabetes complication of peripheral neuropathy (OR 4.01, 95% CI 1.40, 11.48).
      CONCLUSIONS: Acculturation as measured through language is associated with
      diabetes and complications among Hispanics even after controlling for a variety
      of demographic characteristics including health insurance and education. The
      findings suggest that even within a "single" minority ethnic group, there are
      differences in disease prevalence and complications and access to health care.

PMID- 16416700
TI  - Health characteristics of U.S. adults by body mass index category: results from
      NHANES 1999-2002.
AB  - OBJECTIVES: We examined self-reported health characteristics, health care
      utilization, activity patterns, and demographic characteristics of U.S. adults 20
      years and over by body mass index (BMI) category. We hypothesized that overweight
      and obese adults would report fair/poor health more often, report more health
      provider visits annually, experience more joint pain, report greater limitations
      in their daily activities, and report more hours of sedentary leisure-time
      activity than normal-weight adults. METHODS: Self-reported health characteristics
      of U.S. adults from the National Health and Nutrition Examination Survey (NHANES)
      1999-2002 were examined for three BMI categories: normal weight (BMI 18.5-24.9),
      overweight (BMI 25.0-29.9), and obese (BMI > or = 30.0). Covariates included
      gender, race/ethnicity, cigarette smoking, and educational attainment. We
      examined BMI group differences using descriptive and regression methods. RESULTS:
      Compared to normal-weight individuals, overweight individuals reported fair/poor
      health more often, more limitations in daily activities, and more health provider
      contacts. Overweight and obese subjects reported more hours of television
      watching and video game use compared to normal-weight subjects. CONCLUSION: Our
      findings are useful to describe the health characteristics of U.S. adults and may
      be used to anticipate future demand for health services and to support
      intervention programs that help individuals achieve desirable weight status.

PMID- 16416702
TI  - The myth of the actuary: life insurance and Frederick L. Hoffman's race traits
      and tendencies of the American Negro.

PMID- 16416701
TI  - The Pregnancy Risk Assessment Monitoring System (PRAMS): current methods and
      evaluation of 2001 response rates.
AB  - OBJECTIVES: Our objectives were to describe the methodology of the Pregnancy Risk
      Assessment Monitoring System (PRAMS), examine recent response rates, determine
      characteristics associated with response, and track response patterns over time.
      METHODS: PRAMS is a mixed-mode surveillance system, using mail and telephone
      surveys. Rates for response, contact, cooperation, and refusal were computed for
      2001. Logistic regression was used to examine the relationship between maternal
      and infant characteristics and the likelihood of response. Response patterns from
      1996 to 2001 were compared for nine states. RESULTS: The median response rate for
      the 23 states in 2001 was 76% (range: 49% to 84%). Cooperation rates ranged from
      86% to 97% (median 91%); contact rates ranged from 58% to 93% (median 82%).
      Response rates were higher for women who were older, white, married, had more
      education, were first-time mothers, received early prenatal care, and had a
      normal birthweight infant. Education level was the most consistent predictor of
      response, followed by marital status and maternal race. From 1996 to 2001,
      response to the initial mailing decreased in all states compared, but the
      decrease was offset by increases in mail follow-up and telephone response rates.
      Overall response rates remained unchanged. CONCLUSIONS: The PRAMS mail/telephone
      methodology is an effective means of reaching most recent mothers in the 23
      states examined, but some population subgroups are more difficult to reach than
      others. Through more intensive follow-up efforts, PRAMS states have been able to
      maintain high response rates over time despite decreases in response to the
      initial mailing.

PMID- 16416703
TI  - Legal issues in newborn screening: implications for public health practice and
      policy.

PMID- 16416704
TI  - Translating scientific discoveries into public health action: how can schools of
      public health move us forward?

PMID- 16416705
TI  - Sleep and psychiatry.
AB  - Psychiatric disorders constitute 15.4% of the disease burden in established
      market economies. Many psychiatric disorders are associated with sleep
      disturbances, and the relationship is often bidirectional. This paper reviews the
      prevalence of various psychiatric disorders, their clinical presentation, and
      their association with sleep disorders. Among the psychiatric disorders reviewed
      are affective disorders, psychosis, anxiety disorders (including posttraumatic
      stress disorder), substance abuse disorders, eating disorders, and attention
      deficit/hyperactivity disorders. The spectrum of associated sleep disorders
      includes insomnia, hypersomnia, nocturnal panic, sleep paralysis, hypnagogic
      hallucinations, restless legs/periodic limb movements of sleep, obstructive sleep
      apnea, and parasomnias. The effects on sleep of various psychotropic medications
      utilized to treat the above psychiatric disorders are summarized.

PMID- 16416706
TI  - Contribution of sleep research to the development of new antidepressants.
AB  - Several sleep anomalies are known to accompany depression and other psychiatric
      disorders, and to be partially modified by drugs efficient on clinical symptoms.
      Many puzzling theoretical questions remain, even after 30 years of research,
      because these drugs do not act in a uniform way: some reduce slow-wave sleep
      while others increase it some prolong rapid-eye movement sleep latency, while
      others do not. The relationship between insomnia and depression is likely to be a
      close one, since a large majority of patients with depression suffer insomnia,
      and that insomnia can predate depression by a few years. However, questions
      remain here, too, since sleep deprivation is also an effective means to combat
      depression, and some patients present with hypersomnia rather than insomnia. This
      review details the action of all current classes of antidepressants on sleep. It
      examines the predictive value of baseline electronencephalographic sleep symptoms
      or early modifications due to treatment for eventual clinical efficiency. We will
      also discuss the two main theories on the relationship between sleep and
      depression. The action on sleep of all new drugs-and antidepressants in
      particular-is carefully examined during development, for insomnia is currently
      considered to be a major health con-insomnia is currently considered to be a
      major health concern in industrialized countries.

PMID- 16416707
TI  - Alteration of sleep microstructure in psychiatric disorders.
AB  - Macrostructure describes the temporal organization of sleep based on successive
      epochs of conventional length, while microstructure, which is analyzed on the
      basis of the scoring of phasic events, provides additional important dynamic
      characteristics in the evaluation of both normal and pathological sleep
      processes. Relationships between sleep, sleep disorders, and psychiatric
      disorders are quite complex, and it clearly appears that both the macrostructure
      and the microstructure of sleep are valuable physiologically and clinically.
      Psychiatric patients often complain about their sleep, and they may show sleep
      abnormalities that increase with the severity of their illness. Changes in the
      occurrence and frequency of phasic events during sleep may be associated with
      specific psychiatric disorders, and may provide valuable information for both
      diagnosis and prognosis of these disorders.

PMID- 16416708
TI  - Sleep disturbances, psychiatric disorders, and psychotropic drugs.
AB  - Brain neurotransmitter dysfunctions involved in the pathophysiological processes
      of psychiatric disorders are likely to be reflected by concomitant alterations in
      sleep continuity and architecture. Since the corrective effects of psychotropic
      drugs on dysfunctional neurotransmission systems can be evidenced through
      polysomnographic recordings, one may consider sleep as a kind of "window" on the
      neurobiology of psychiatric disorders. During the last 10 years, major
      breakthroughs in our understanding of sleep-wake mechanisms have provided some
      indications on how psychotropic drugs could influence the sleep-wake cycle. In
      this review, recent inroads into the understanding of sleep regulatory neural
      mechanisms are introduced and discussed in terms of the effects of psychotropic
      drugs. The relationship between the pathophysiological process of a disease, its
      consequence on sleep, and the corrective effect of a psychotropic drug are
      exemplified by two psychopathological states: substance withdrawal and major
      depression. One may conclude that polysomnographic recordings are a unique
      noninvasive tool to analyze brain functioning, and are particularly well suited
      to evaluating the objective effects of new psychotropic drugs.

PMID- 16416710
TI  - Hypersomnia.
AB  - Hypersomnia, a complaint of excessive daytime sleep or sleepiness, affects 4% to
      6% of the population, with an impact on the everyday life of the patient
      Methodological tools to explore sleep and wakefulness (interview, questionnaires,
      sleep diary, polysomnography, Multiple Sleep Latency Test, Maintenance of
      Wakefulness Test) and psychomotor tests (for example, psychomotor vigilance task
      and Oxford Sleep Resistance or Osler Test) help distinguish between the causes of
      hypersomnia. In this article, the causes of hypersomnia are detailed following
      the conventional classification of hypersomnic syndromes: narcolepsy, idiopathic
      hypersomnia, recurrent hypersomnia, insufficient sleep syndrome, medication- and
      toxin-dependent sleepiness, hypersomnia associated with psychiatric disorders,
      hypersomnia associated with neurological disorders, posttraumatic hypersomnia,
      infection (with a special emphasis on the differences between bacterial and viral
      diseases compared with parasitic diseases, such as sleeping sickness) and
      hypersomnia, hypersomnia associated with metabolic or endocrine diseases,
      breathing-related sleep disorders and sleep apnea syndromes, and periodic limb
      movements in sleep.

PMID- 16416711
TI  - Behavioral and psychiatric consequences of sleep-wake schedule disorders.
AB  - Circadian rhythm sleep disorders (CRSDs) arise when an individual's sleep-wake
      rhythm mismatches the environmental 24-h schedule. Physiological data and genetic
      studies in patients with CRSDs suggest that these disorders result from abnormal
      functioning of the circadian timing system. Diagnosis involves recognition of the
      characteristics of CRSDs, which can be achieved by clinical interview and
      actigraphic monitoring of rest-activity patterns. Bright-light therapy and
      melatonin administration have proved to be the most effective treatment
      modalities of CRSDs. In psychiatric practice, CRSDs can be encountered on various
      occasions. Some evidence indicates that a deviant sleep-wake schedule might be a
      predisposing factor to personality disorders. CRSDs can emerge as an iatrogenic
      effect of certain psychoactive drugs, such as haloperidol and fluvoxamine. It is
      not uncommon that the daytime functional difficulties that accompany CRSDs are
      misinterpreted as symptoms of psychopathology. Recognition and awareness of these
      disorders should prevent years of erroneous diagnosis and treatment in these
      patients.

PMID- 16416712
TI  - The dental implications of bisphosphonates and bone disease.
AB  - In 2002/2003 a number of patients presented to the South Australian Oral and
      Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the
      jaws. All were middle-aged to elderly, medically compromised and on
      bisphosphonates for bone pathology. Review of the literature showed similar cases
      being reported in the North American oral and maxillofacial surgery literature.
      This paper reviews the role of bisphosphonates in the management of bone disease.
      There were 2.3 million prescriptions for bisphosphonates in Australia in 2003.
      This group of drugs is very useful in controlling bone pain and preventing
      pathologic fractures. However, in a small number of patients on bisphosphonates,
      intractable, painful, non-healing exposed bone occurs following dental
      extractions or denture irritation. Affected patients are usually, but not always,
      over 55 years, medically compromised and on the potent nitrogen containing
      bisphosphonates pamidronate (Aredia/Pamisol), alendronate (Fosamax) and
      zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no
      simple, effective treatment and the painful exposed bone may persist for years.
      The main complications are marked weight loss from difficulty in eating and
      severe jaw and neck infections. Possible preventive and therapeutic strategies
      are presented although at this time there is no evidence of their effectiveness.
      Dentists must ask about bisphosphonate usage for bone disease when recording
      medical histories and take appropriate actions to avoid the development of this
      debilitating condition in their patients.

PMID- 16416713
TI  - Drugs for pain management in dentistry.
AB  - Pain is one of the most common reasons patients seek dental treatment. It may be
      due to many different diseases/conditions or it may occur after treatment.
      Dentists must be able to diagnose the source of pain and have strategies for its
      management. The '3-D's' principle--diagnosis, dental treatment and drugs--should
      be used to manage pain. The first, and most important, step is to diagnose the
      condition causing the pain and identify what caused that condition. Appropriate
      dental treatment should then be undertaken to remove the cause of the condition
      as this usually provides rapid resolution of the symptoms. Drugs should only be
      used as an adjunct to the dental treatment. Most painful problems that require
      analgesics will be due to inflammation. Pain management drugs include non
      narcotic analgesics (e.g., non-steroidal anti-inflammatory drugs, paracetamol,
      etc) or opioids (i.e., narcotics). Non-steroidal anti-inflammatory drugs (NSAIDs)
      provide excellent pain relief due to their anti-inflammatory and analgesic
      action. The most common NSAIDs are aspirin and ibuprofen. Paracetamol gives very
      effective analgesia but has little anti-inflammatory action. The opioids are
      powerful analgesics but have significant side effects and therefore they should
      be reserved for severe pain only. The most commonly-used opioid is codeine,
      usually in combination with paracetamol. Corticosteroids can also be used for
      managing inflammation but their use in dentistry is limited to a few very
      specific situations.

PMID- 16416709
TI  - Psychiatric aspects of organic sleep disorders.
AB  - In recent years, a number of studies have attempted to characterize psychological
      disturbances related to various sleep disorders. The objective of this type of
      research is to investigate the possibility that psychopathology may represent an
      etiological factor, a complication, and/or a target for treatment. In addition,
      disordered sleep can present itself in a complex and atypical fashion in which
      the primary sleep-related component may not be immediately apparent. This article
      reviews the evidence for a relationship between organic sleep disorders and
      psychiatric morbidity. Generally, it can be concluded that organic sleep
      disorders have a profound negative impact on most domains of health-related
      quality of life. Results for the sleep disorders that have been studied
      (narcolepsy idiopathic hypersomnia, sleep apnea/hypopnea syndrome, restless legs
      syndrome, periodic limb movement disorder, and circadian sleep disorders) show
      strong evidence for an association with mood disorders. After treatment,
      depression scores may or may not improve to the level of population norms,
      suggesting that this relationship is more complex than one of mere cause and
      effect.

PMID- 16416714
TI  - A concise review of the basic biology and pharmacology of local analgesia.
AB  - Local analgesics are the most commonly used group drugs in dental practice.
      However, due to their frequent use and high margin of safety, often dental
      practitioners neglect to properly understand the biology and pharmacology of
      these drugs. This article reviews the basic concepts of pain, pain pathways, the
      mode of action of local analgesics and factors which affect their usage. Specific
      details and properties of some currently available solutions are also outlined. A
      greater understanding of the biology and pharmacology of local anaesthetics will
      ultimately lead to safer and more effective use in everyday clinical practice.

PMID- 16416715
TI  - Oral viral infections and the therapeutic use of antiviral agents in dentistry.
AB  - This paper reviews the current concepts of viral classification, infection and
      replication. The clinical presentation of common oral viral infections
      encountered in the dental practice are discussed, including: herpes simplex virus
      types 1 and 2; Epstein-Barr virus; varicella-zoster virus; Coxsackie virus; human
      papilloma virus; and human immunodeficiency virus. The diagnosis, principles of
      management and pharmacological agents available for the treatment of oral viral
      infections are also discussed.

PMID- 16416716
TI  - Oral candidosis and the therapeutic use of antifungal agents in dentistry.
AB  - This paper reviews the current concepts of mycology and candidal infections as
      they relate to the oral cavity. Proposed classification for the presentation of
      oral candidosis is outlined as are examples of these topical infections, such as
      erythematous, pseudomembranous and hyperplastic candidosis, as well as angular
      chelitis and median rhomboid glossitis. The diagnosis and principles of
      management of oral candidosis are discussed, the therapeutic agents available for
      the management of these infections are presented and a treatment protocol for the
      management of patients with oral candidosis is given.

PMID- 16416717
TI  - Topical corticosteroids in dental practice.
AB  - Topical corticosteroids represent an important therapeutic aid in the management
      of a range of oral mucosal disease conditions. Like all medications, their
      successful use depends upon an understanding of the disease process. This
      includes an appropriate diagnosis, a clear view of the desirable treatment
      outcomes and knowledge of whether treatment is aimed at management of a chronic
      disease or enhanced resolution of a short-term condition. This paper reviews the
      use of topical corticosteroids and their possible roles in the management of oral
      disease.

PMID- 16416718
TI  - Patients with artificial joints: do they need antibiotic cover for dental
      treatment?
AB  - This study reviews whether patients with artificial joints need antibiotic cover
      for dental treatment. Generally in Australia the practice has developed of giving
      most patients with artificial joints antibiotic prophylaxis for a wide range of
      dental procedures. This is partly on anecdotal grounds, partly historical and
      partly for legal concerns. It has been encouraged by some guidelines.
      Scientifically, the risk and the benefit of each step in the process needs to be
      analysed. This review shows that the risk of an artificial joint becoming
      infected from a bacteraemia of oral origin is exceedingly low whereas the risk of
      an adverse reaction to the antibiotic prophylaxis is higher than the risk of
      infection. If all patients with artificial joints receive antibiotic prophylaxis
      then more will die from anaphylaxis than develop infections. Factors which
      balance the risk benefit are if the patient is seriously immunocompromised, if
      the joint prosthesis is failing or chronically inflamed and if the dental
      procedures, such as from extractions and deep periodontal scaling, produce high
      level bacteraemias. Recommendations to rationalize antibiotic prophylaxis for
      patients with artificial joints are presented.

PMID- 16416719
TI  - Antibiotic prophylaxis for dentoalveolar surgery: is it indicated?
AB  - Usually dentists in Australia give patients oral antibiotics after dentoalveolar
      surgery as a prophylaxis against wound infection. When this practice is compared
      to the principle of antibiotic prophylaxis in major surgery it is found to be at
      variance in a number of ways. In major surgery, the risk of infection should be
      high, and the consequences of infection severe or catastrophic, before antibiotic
      prophylaxis is ordered. If it is provided then a high dose of an appropriate
      spectrum antibiotic must be present in the blood prior to the first incision.
      Other factors which need to be considered are the degree of tissue trauma, the
      extent of host compromise, other medical comorbidities and length of
      hospitalization. Standardized protocols of administration have been determined
      and evaluated for most major surgical procedures. Dentoalveolar surgery is
      undoubtedly a skilled and technically challenging procedure. However, in contrast
      to major surgical procedures, it has a less than five per cent infection rate and
      rarely has severe adverse consequences. Dentoalveolar surgery should be of short
      duration with minimal tissue damage and performed in the dental chair under local
      anaesthesia. Controlled studies for both mandibular third molar surgery and
      placement of dental implants show little or no evidence of benefit from
      antibiotic prophylaxis and there is an adverse risk from the antibiotic. This
      review concludes that there is no case for antibiotic prophylaxis for most
      dentoalveolar surgery in fit patients. In the few cases where it can be
      considered, a single high preoperative dose should be given.

PMID- 16416720
TI  - Antibiotic prophylaxis for endocarditis: time to reconsider.
AB  - Some cardiac conditions require antibiotic prophylaxis for some types of dental
      treatment to reduce the risk of infective endocarditis (IE). All medical and
      dental practitioners are familiar with this practice but tend to use different
      regimens in apparently similar circumstances. Generally, the trend has been to
      prescribe antibiotics if in doubt. This review explores the evidence for
      antibiotic prophylaxis to prevent IE: does it work and is it safe? The changing
      nature of IE, the role of bacteraemia of oral origin and the safety of
      antibiotics are also reviewed. Most developed countries have national guidelines
      and their points of similarity and difference are discussed. One can only agree
      with the authority who describes antibiotic guidelines for endocarditis as being
      'like the Dead Sea Scrolls, they are fragmentary, imperfect, capable of various
      interpretations and (mainly) missing!' Clinical case-controlled studies show that
      the more widely antibiotics are used, the greater the risk of adverse reactions
      exceeding the risk of IE. However, the consensus is that antibiotic prophylaxis
      is mandatory for a small number of high-risk cardiac and high-risk dental
      procedures. There are a large number of low-risk cardiac and dental procedures in
      which the risk of adverse reactions to the antibiotics exceeds the risk of IE,
      where prophylaxis should not be provided. There is an intermediate group of
      cardiac and dental procedures for which careful individual evaluation should be
      made to determine whether IE or antibiotics pose the greater risk. These
      categories are presented. All medical and dental practitioners need to reconsider
      their approach in light of these current findings.

PMID- 16416721
TI  - Cardiac murmurs: echocardiography in the assessment of patients requiring
      antibiotic prophylaxis for dental treatment.
AB  - BACKGROUND: Traditionally patients who indicate that they have a heart murmur or
      who indicate that they have had rheumatic fever are given antibiotic prophylaxis
      for dental treatment. This is commonly done without further assessment of the
      patient's actual endocarditis risk. Echocardiography is a non-invasive method of
      assessing cardiac valve function and haemodynamics. METHODS: Consecutive patients
      who were referred to a private practice oral and maxillofacial surgeon for
      dentoalveolar surgery and indicated that they had a cardiac problem and usually
      had antibiotic prophylaxis, were evaluated. Those with a clear indication for
      prophylaxis, for example had prosthetic heart valves or previous infective
      endocarditis, received antibiotic prophylaxis. Where there was uncertainty, they
      were referred for an echocardiogram, and if abnormal, a formal cardiology review.
      RESULTS: Three hundred and seventy patients out of approximately 20 000 (1.85 per
      cent) indicated that they had a cardiac murmur and usually received antibiotic
      prophylaxis for dental treatment between 1 February 1997 and 1 February 2005. Two
      hundred and sixty-two (71 per cent) were female and 108 (29 per cent) were male;
      age range 0.7 to 98 years, average 37.6 years. Two hundred and seventy (72 per
      cent) had normal hearts with no indication for antibiotic prophylaxis. Of the 100
      (28 per cent) patients with abnormal findings, they were on average older; 49.5
      years, range 0.7 to 87 years. Of these, 50 (14 per cent) met current indications
      for antibiotic prophylaxis. CONCLUSION: Patients who present for dental treatment
      indicating that they require antibiotic prophylaxis for cardiac condition need to
      be fully evaluated. In this study only 50 of 370 patients (14 per cent) required
      antibiotic prophylaxis. The remaining 320 (86 per cent) would have no benefit but
      a risk of adverse reaction to the antibiotic.

PMID- 16416722
TI  - Severe odontogenic infections.
AB  - BACKGROUND: Severe odontogenic infections are serious potentially lethal
      conditions. Following the death of a patient in the authors' institution this
      study was initiated to determine the risk factors, management and outcome of a
      consecutive series of patients. METHODS: All patients admitted to the Royal
      Adelaide Hospital under the care of the Oral and Maxillofacial Surgery Unit with
      odontogenic infections in calendar year 2003 were investigated. Detailed
      information relative to their pre-presentation history, surgical and anaesthetic
      management and outcome was obtained and analysed. RESULTS: Forty-eight patients,
      32M, 16F, average age 34.5, range 19 to 88 years were treated. All presented with
      pain and swelling, with 21 (44 per cent) having trismus. Forty-four (92 per cent)
      were as a result of dental neglect and four (8 per cent) were regular dental
      patients having endodontic treatment which failed. Of those known to have been
      treated prior to presentation, most had been on antibiotics. Most patients had
      aggressive surgical treatment with extraction, surgical drainage, high dose
      intravenous antibiotics and rehydration. The hospital stay was 3.3 (range 1-16)
      days. Patients requiring prolonged intubation and high dependency or intensive
      care (40 per cent) had longer hospitalization. No patient died and all fully
      recovered. CONCLUSION: Severe odontogenic infections are a serious risk to the
      patient's health and life. Management is primarily surgical with skilled
      anaesthetic airway management. Antibiotics are required in high intravenous doses
      as an adjunct and not as a primary treatment.

PMID- 16416723
TI  - [Atrial fibrillation].

PMID- 16416724
TI  - [Reconvalescence in Goethes "Wilhelm Meister"].

PMID- 16416725
TI  - [Goethe and the heart].

PMID- 16416726
TI  - [Goethes scientific method and modern medicine].

PMID- 16416727
TI  - ["A man is being made"].

PMID- 16416729
TI  - [Solution to the medical image puzzle].

PMID- 16416728
TI  - [CME radiology solution. Known coronary heart disease, myocardial infarct].

PMID- 16416730
TI  - Endometrial cells and the Papanicolaou test.

PMID- 16416731
TI  - The clinical significance of benign-appearing endometrial cells on a Papanicolaou
      test in women 40 years or older.
AB  - The 2001 Bethesda System revision recommends reporting benign-appearing
      endometrial cells (BAEMC) in all women 40 years or older, not just in
      postmenopausal women. We studied the influence of this change on clinical
      practice and the detection of endometrial neoplasia. Women 40 years or older were
      selected for study if BAEMC were reported on a cervical cytologic specimen. Cases
      were stratified by implementation of the 2001 guidelines. Results of endometrial
      biopsies within 18 months, with special attention to the frequency of
      adenocarcinoma and hyperplasia, were assessed. In the preimplementation group,
      BAEMC were reported as an epithelial cell abnormality in 154 postmenopausal women
      and as an incidental finding in 636 premenopausal women (total = 790). In the
      postimplementation group, BAEMC were reported in 836 women. The proportion of
      endometrial biopsies in these cohorts was significantly increased (P < .05).
      After implementation of the 2001 guidelines, the detection of endometrial cancer
      increased (6 vs 3 cases, not significant). Of the women with cancer, 3 were
      premenopausal, 5 were asymptomatic, and 2 were premenopausal and asymptomatic.
      All cancers were identified in women older than 45 years, suggesting that the
      Bethesda cutoff of 40 years is safe and conservative.

PMID- 16416732
TI  - Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in
      normal pancreas and chronic pancreatitis.
AB  - Mesothelin, a cell surface glycoprotein present on normal mesothelial cells, has
      been reported to be expressed in pancreatic adenocarcinomas. We conducted this
      study to fully characterize mesothelin expression in surgically resected,
      formalin-fixed, paraffin-embedded tissue specimens of 18 pancreatic
      adenocarcinomas, 9 adenocarcinomas of the ampulla of Vater, 12 adenocarcinomas of
      the common bile duct, and 17 cases of chronic pancreatitis. Mesothelin
      immunostaining was performed using the antimesothelin monoclonal antibody 5B2.
      All 18 cases (100%) of pancreatic adenocarcinomas showed mesothelin expression,
      as did 8 (89%) of 9 cases of ampullar adenocarcinoma and all 12 cases (100%) of
      common bile duct adenocarcinoma. In all cases of pancreaticobiliary
      adenocarcinoma, the adjacent normal pancreas did not stain for mesothelin. Of 17
      specimens of chronic pancreatitis, 16 were negative for mesothelin expression,
      and 1 case showed weak mesothelin staining of fewer than 5% of normal pancreatic
      ducts. Our results demonstrated mesothelin expression in the majority of
      pancreaticobiliary adenocarcinomas and no expression in normal pancreatic tissues
      and in chronic pancreatitis.

PMID- 16416733
TI  - Iron accumulation in chronic hepatitis C: relation of hepatic iron distribution,
      HFE genotype, and disease course.
AB  - The aim of the present study was to describe the histopathologic features of
      hepatic iron accumulation in patients with chronic hepatitis C (CH-C) infection,
      the relation between HFE mutations and hepatic iron location and among iron
      distribution, HFE, and hepatic damage. We studied 206 patients with CH-C
      infection. Of 101 patients with hemosiderin deposits, 90.1% had iron deposits in
      hepatocytes (alone or with sinusoidal and/or portal involvement). The hepatic
      iron score increased significantly as iron accumulation involved sinusoidal and
      portal tract compartments and according to HFE genotypes. Severe fibrosis and
      cirrhosis were associated more markedly with the presence of hemosiderin iron in
      the 3 hepatic compartments, HFE mutations, and high alcohol intake. We suggest
      that part of the iron accumulation in CH-C infection derives from increased iron
      absorption and release from storage cells and that the amount and distribution of
      hepatic iron deposits is related to hepatic damage. HFE mutations favor both
      processes, but other factors, genetic or acquired, are involved.

PMID- 16416734
TI  - Analysis of polyomavirus-infected renal transplant recipients' urine specimens:
      correlation of routine urine cytology, fluorescence in situ hybridization, and
      digital image analysis.
AB  - Urinary polyomavirus subtype BK (BKV)-infected urothelial and renal tubular
      cells, "decoy cells," have been shown to be aneuploid with digital image analysis
      (DIA). We wanted to determine whether decoy cells cause false-positive
      fluorescence in situ hybridization (FISH) results in BKV-infected urine samples.
      Urine samples from 38 renal transplant recipients were split 3 ways and evaluated
      for number of decoy cells per 10 high-power fields by routine cytology, total
      nuclear DNA content by DIA, and chromosomal abnormalities by FISH. For DIA,
      Feulgen-stained cells were quantified with a CAS 200 image analyzer (Bacus
      Laboratories, Lombard, IL), and for FISH, the UroVysion probe set (Vysis, Downers
      Grove, IL) consisting of chromosome enumeration probes 3, 7, 17, and locus
      specific identifier probe 9p21 (p16 gene) was used. Of the 38 specimens, 32
      (84.2%) had evidence of BKV infection by routine cytology. DIA and FISH results
      were aneuploid/aneusomic in 30 (93.8%) and 4 (12.5%) cases, respectively. All
      aneusomic FISH specimens occurred in men older than 52 years of age and who also
      had 4 of the 6 highest PCR-BKV titers. To date, no patient has clinical evidence
      of malignancy. The 6 specimens without decoy cells were DNA diploid/disomic by
      DIA and FISH. Abnormal FISH results of urinary decoy cells occur much less
      frequently than aneuploidy by DIA in renal transplant recipients and might merit
      close follow-up in some transplant recipients.

PMID- 16416735
TI  - Immunohistochemical staining for cyclin D1 and Ki-67 aids in the stratification
      of atypical ductal hyperplasia diagnosed on breast core biopsy.
AB  - A diagnosis of atypical ductal hyperplasia (ADH) after breast core biopsy usually
      is followed by an excisional biopsy to exclude the presence of a more significant
      lesion. To determine whether the immunohistochemical expression of cyclin D1
      (CyD1) and Ki-67 can aid in case stratification for the likelihood of finding
      ductal carcinoma in situ (DCIS) on subsequent excision, we immunohistochemically
      stained 21 consecutive ADH cases diagnosed by core biopsy, and proliferation
      indices (PIs) were calculated for each case. Fluorescence in situ hybridization
      to detect CCND1 amplification was performed in 10 cases. In 5 cases, DCIS (with
      or without invasive carcinoma) was identified in the subsequent excision. The
      mean PICyD1 and PIKi-67 for these cases were significantly higher than in the
      remainder (P = .03 and P = .05, respectively). The sensitivities of PICyD1 and
      PIKi-67 for the presence of DCIS on subsequent excision were 100%, and the
      specificities were 75% and 69%, respectively. The specificity of the 2 markers
      combined was 88%. The number of cells with CCND1 amplification was higher in
      cases with DCIS or ADH on subsequent excision. Immunostaining for CyD1 and Ki-67
      might help stratify cases of ADH on core biopsy and identify patients unlikely to
      have DCIS found on excision.

PMID- 16416736
TI  - AP-2gamma protein expression in intratubular germ cell neoplasia of testis.
AB  - Although activator protein 2gamma (AP-2gamma) has been reported to be a marker of
      germ cell tumors of the testis, its relationship to placental alkaline
      phosphatase (PLAP) and KIT (CD117) protein expression in intratubular germ cell
      neoplasia (ITGCN) has not been directly compared. In this study, staining of AP
      2gamma in 30 cases of ITGCN was examined and compared with that of PLAP and KIT.
      Both PLAP and KIT were positive in 29 (97%) of 30 cases, whereas AP-2gamma was
      expressed in 100%. All 3 markers were negative in normal testis (0 of 11 cases).
      DNA binding sites in the promoter region forAP-2gamma in the PLAP and c-kit genes
      might explain the concordance of protein expression.

PMID- 16416737
TI  - Comparison of disagreement and error rates for three types of interdepartmental
      consultations.
AB  - Previous studies have documented a relatively high rate of disagreement for
      interdepartmental consultations, but follow-up is limited. We reviewed the
      results of 3 types of interdepartmental consultations in our hospital during a 2
      year period, including 328 incoming, 928 pathologist-generated outgoing, and 227
      patient- or clinician-generated outgoing consults. The disagreement rate was
      significantly higher for incoming consults (10.7%) than for outgoing pathologist
      generated consults (5.9%) (P = .06). Disagreement rates for outgoing patient- or
      clinician-generated consults were not significantly different from either other
      type (7.9%). Additional consultation, biopsy, or testing follow-up was available
      for 19 (54%) of 35, 14 (25%) of 55, and 6 (33%) of 18 incoming, outgoing
      pathologist-generated, and outgoing patient- or clinician-generated consults with
      disagreements, respectively; the percentage of errors varied widely (15/19 [79%],
      8/14 [57%], and 2/6 [33%], respectively), but differences were not significant (P
      >.05 for each). Review of the individual errors revealed specific diagnostic
      areas in which improvement in performance might be made. Disagreement rates for
      interdepartmental consultation ranged from 5.9% to 10.7%, but only 33% to 79%
      represented errors. Additional consultation, tissue, and testing results can aid
      in distinguishing disagreements from errors.

PMID- 16416738
TI  - Improving the quality of cytology diagnosis: root cause analysis for errors in
      bronchial washing and brushing specimens.
AB  - Detailed root cause analysis to determine causes of pulmonary cytology errors has
      not been used to design specific practice changes. We performed root cause
      analysis of all false-negative bronchial brushing and washing specimen errors (n
      = 32) detected by the cytologic-histologic correlation process in 2002. Medical
      records and all slides were reviewed. Based on the correlation process, 10 errors
      were interpretive, 16 sampling, and 6 combined interpretive/sampling. Root cause
      analysis showed that the lesion was not accessible in 8 cases and tumor was
      readily identified on the slides in only 1 case. In 11 cases, the malignant cells
      were few and not recognized, and in 13 cases, obscuring artifacts (eg, cellular
      crushing and air drying) limited interpretation. Sampling issues had a major role
      in the misdiagnosis in 31 cases (97%), and recommendations for error reduction
      include immediate interpretation and the use of transmucosal fine-needle
      aspiration.

PMID- 16416739
TI  - A simplified algorithm for the laboratory detection of lupus anticoagulants:
      utilization of two automated integrated tests.
AB  - Diagnosis of antiphospholipid antibody syndrome includes laboratory testing for
      lupus anticoagulants (LAs). Guidelines for testing have been published, but
      approaches vary, often incorporating multiple tests. We evaluated the performance
      of the activated partial thromboplastin time using 2 reagents, a dilute Russell
      viper venom time, and a hexagonal phospholipid assay for detecting LAs in 105
      adults. Of the patients, 26 were taking anticoagulants at the time of testing.
      Based on findings, an algorithm was derived for optimal detection of LAs using 2
      easily performed, automated, integrated test systems. Of 105 patient samples, 30
      (28.6%) were positive for LAs, using the algorithm interpretive criteria. Of
      these 30 positive results, 10 were detected in the 26 patients taking
      anticoagulants. Analysis by chi2 showed no difference in performance of the
      integrated tests between samples from patients taking and not taking
      anticoagulants. The algorithm is offered as a means for standardization of
      laboratory testing for LAs.

PMID- 16416740
TI  - Clinically relevant differences in prothrombin time and INR values related to
      blood sample collection in plastic vs glass tubes.
AB  - We compared prothrombin times (PTs) and international normalized ratios (INRs)
      for blood samples drawn into plastic vs glass collection tubes. We collected 60
      venous blood samples into 4.5-mL glass and 2 plastic tubes (2.7 and 3.5 mL). An
      additional 153 samples, including 63 from warfarin-anticoagulated patients, were
      collected only in glass and 2.7-mL plastic tubes. The PTs and INRs were
      determined following routine laboratory procedures. A subset of 35 frozen aliquot
      samples was analyzed with a different instrument-reagent combination. The PTs and
      INRs for samples in plastic tubes were significantly lower than for samples in
      glass tubes. The mean INR differences increased with INR magnitude from
      approximately -0.1 (INR, 1.5) to -0.7 (INR, 4.5). Of the plastic tube INRs, 50%
      were more than 10% lower than INRs from samples collected in glass tubes.
      Therapeutic monitoring based on plastic-tube INRs could result in higher doses of
      warfarin.

PMID- 16416741
TI  - Reassessment of ABO blood group, sex, and age on laboratory parameters used to
      diagnose von Willebrand disorder: potential influence on the diagnosis vs the
      potential association with risk of thrombosis.
AB  - We reassessed the influence of ABO blood group, sex, and age on plasma levels of
      von Willebrand factor (vWF) antigen, vWF:ristocetin cofactor, vWF:collagen
      binding assay, and factor VIII coagulant (FVIII:C). Data show that levels of vWF
      and FVIII:C increase with increasing age (P < .001 for all parameters) and that
      the ABO blood group influences plasma levels such that O group levels are
      significantly less than non-O group levels. There was no significant association
      with sex and Rh status. The selection of normal ranges based on ABO blood groups
      may influence the clinical diagnosis of von Willebrand disease (vWD) but might
      not be clinically relevant or help identify people at increased risk of bleeding.
      Differences in ABO-related ranges were more extensive at the high end of the
      ranges. This is of particular interest because high levels of vWF and FVIII are
      associated with thrombosis risk, and an ABO relationship also has been described.
      O group individuals may or may not be at greater risk for bleeding (they have
      lower levels of vWF and FVIII:C) and are more likely to be diagnosed with vWD. It
      also is possible that O group status may be protective for thrombosis.

PMID- 16416742
TI  - Proteomic profiling of mature CD10+ B-cell lymphomas.
AB  - Proteomic profiling with protein-chip technology has been used successfully to
      discover biomarkers with potential clinical usefulness in several cancer types.
      Little proteomic study has been done in B-cell lymphomas. We determined whether
      the expression of a set of proteins by protein-chip technology coupled with new
      informatics tools could be used to build a model to molecularly classify B-cell
      lymphoma subgroups. We used surface-enhanced laser desorption/ionization time-of
      flight mass spectrometry to analyze 18 CD10+ B-cell lymphomas, including 6 grade
      1 (G1) follicular lymphomas (FLs), 7 grade 3 (G3) FLs, and 5 Burkitt lymphomas.
      We used 7 reactive follicular hyperplasia cases as a control group. By using SAX2
      ProteinChip arrays (Ciphergen Biosystems, Fremont, CA), we found a unique protein
      expression profile for each type of lesion. Two-way hierarchical clustering
      analysis of these protein expression profiles differentiated reactive follicular
      hyperplasia, FL, and Burkitt lymphoma, with 5 major clusters of differentially
      expressed protein peaks. In addition, we identified histone H4 as a potential
      differentially expressed protein marker that seems to distinguish G1 from G3 FL.
      To our knowledge, this is the first proteomic study using protein-chip technology
      for molecular classification of B-cell lymphoma subtypes with clinical samples.

PMID- 16416743
TI  - Flow cytometric analysis of different CD14 epitopes can help identify immature
      monocytic populations.
AB  - Accurate diagnosis of monocytic neoplasms often is dependent on quantitating
      monoblasts, promonocytes, and monocytes. However, distinguishing these
      populations by morphologic assessment alone can be difficult and subject to
      significant intraobserver variability. We evaluated a 4-color flow cytometry
      technique using different anti-CD14 antibodies that recognize the MO2 and MY4
      epitopes to identify monoblasts, promonocytes, and monocytes. Normal control
      specimens and 18 cases of monocytic neoplasia were evaluated and results
      correlated with morphologic findings. We found the MY4 epitope first appearing at
      the early promonocyte stage and the MO2 epitope appearing only on mature
      monocytes after the promonocyte stage. Expression of the MY4 and MO2 epitopes by
      neoplastic monocyte populations was found to usually parallel the normal monocyte
      differentiation patterns, although exceptions were noted. Our study suggests that
      4-color flow cytometry may be an especially useful adjunct for morphologically
      difficult cases by providing an immunophenotypic measure of neoplastic monoblasts
      and promonocytes.

PMID- 16416744
TI  - T-cell large granular lymphocyte leukemias have multiple phenotypic abnormalities
      involving pan-T-cell antigens and receptors for MHC molecules.
AB  - T-cell large granular lymphocyte (T-LGL) leukemias represent monoclonal T-cell
      expansions that express CD16, CD56, or CD57 and cause cytopenias. The
      identification of T-LGL leukemias can be difficult because reactive T-LGL cells
      also can express CD16, CD56, and CD57, and many leukemia cases show only mild
      lymphocytoses. In this study, 23 T-LGL leukemia cases were analyzed by 3- and 4
      color flow cytometry to identify markers that could aid in discriminating
      leukemic from normal T-LGL. In most cases (18/23), abnormalities (bright, dim, or
      negative expression) of 2 or more pan-T-cell antigens were identified, with all
      cases showing abnormal CD5 levels. Abnormal expression of CD94 was identified in
      22 of 23 cases, and 15 of 21 cases also showed abnormal expression of class 1 MHC
      receptor molecules identified by antibodies against CD158a, CD158b, CD158e,
      CD158i, CD158k, and CD94. These studies help define abnormal phenotypic features
      typical of T-LGL leukemia that may have important diagnostic value.

PMID- 16416745
TI  - Cold-dependent loss of factor VIII von Willebrand factor activities in citrated
      whole blood is reversed by rewarming.

PMID- 16416746
TI  - The coming flu pandemic?

PMID- 16416747
TI  - Malocclusion and uptake of orthodontic treatment in Taranaki 12-13-year-olds.
AB  - OBJECTIVES: To describe the occurrence of malocclusion and the uptake of
      orthodontic treatment among 12-13-year-olds in the province of Taranaki, New
      Zealand. DESIGN: Cross-sectional descriptive study using a random sample of 12-13
      year-olds attending Intermediate schools. METHODS: Parents or caregivers
      completed a postal questionnaire. Children (N = 430; participation rate 74.1
      percent) completed a questionnaire and were dentally examined. MAIN OUTCOME
      MEASURES: Malocclusion, using the Dental Aesthetic Index, or DAI (Cons et al,
      1986), recorded by a single calibrated examiner, and the use of orthodontic
      services as reported by parents or caregivers. RESULTS: The mean DAI score was
      28.3 (sd = 7.8). Females and non-Maori had greater mean DAI scores than males and
      Maori, respectively. A high proportion of the children needed orthodontic
      treatment (60.5 percent in the "definite", "severe" or "handicapping"
      categories), and 17 percent had a "handicapping" malocclusion. While over one
      third of the children had been advised to seek an orthodontic consultation, a
      proportion (23.4 percent) did not. Of those who did, a similar proportion did not
      proceed with care because of financial considerations. Children of low socio
      economic status (SES) were disproportionately represented in these groups.
      Children with "severe" or "handicapping" malocclusions who did not proceed with
      treatment came predominantly from low-SES households and high-deprivation areas.
      CONCLUSIONS: Cost was a barrier to orthodontic treatment for low-SES, high
      deprivation children and Maori. Social and ethnic inequalities exist in
      orthodontic treatment need in Taranaki. The utilisation of orthodontic treatment
      appeared to be largely neither equitable nor rational.

PMID- 16416749
TI  - DDE index.

PMID- 16416748
TI  - Radiographic recognition and distribution of approximal carious lesions in New
      Zealand undergraduate dental students.
AB  - Bitewing radiographs are widely used to detect caries on the approximal surfaces
      of teeth. The aim of this study was to determine the prevalence of approximal
      caries in an educated young adult (New Zealand dental student) population, and to
      compare the diagnostic decisions of students and university teachers. A total of
      123 students aged from 18 to 25 years (mean age 21 years) participated, having
      given their informed consent. Their bitewings were digitised and assessed for
      approximal carious lesions from the distal surface of the first premolars to the
      mesial surface of the second molars on the same computer screen. The following
      criteria were used: (0) no detectable radiolucency, (R1) lesion confined to the
      outer half of the enamel, (R2) lesion into the inner half of the enamel, (R3)
      lesion into the outer half of dentine along the amelodentinal junction, (R4)
      lesion beyond the outer part of the dentine. The views were assessed by two final
      year dental students and two experienced university teachers, and results were
      compared. A total of 2710 surfaces were examined; restored and missing surfaces
      (tooth absent, off film or surface unreadable) were excluded. Carious lesions
      were found in 173 (6.38 percent) of the surfaces. Only 57 subjects presented with
      carious lesions radiographically, but 16 (13 percent) of subjects had 87 percent
      of all the lesions. Seventy-nine percent of the lesions were enamel lesions (R1
      and R2), with 21 percent of the lesions having dentine involvement (R3 and R4).
      Inter-examiner agreement was high, Pearson's correlation coefficient r = 0.8237,
      and Cohen's kappa kappa = 0.76.

PMID- 16416750
TI  - The mental and physical health outcomes of green exercise.
AB  - Both physical activity and exposure to nature are known separately to have
      positive effects on physical and mental health. We have investigated whether
      there is a synergistic benefit in adopting physical activities whilst being
      directly exposed to nature ('green exercise'). Five groups of 20 subjects were
      exposed to a sequence of 30 scenes projected on a wall whilst exercising on a
      treadmill. Four categories of scenes were tested: rural pleasant, rural
      unpleasant, urban pleasant and urban unpleasant. The control was running without
      exposure to images. Blood pressure and two psychological measures (self-esteem
      and mood) were measured before and after the intervention. There was a clear
      effect of both exercise and different scenes on blood pressure, self-esteem and
      mood. Exercise alone significantly reduced blood pressure, increased self-esteem,
      and had a positive significant effect on 4 of 6 mood measures. Both rural and
      urban pleasant scenes produced a significantly greater positive effect on self
      esteem than the exercise-only control. This shows the synergistic effect of green
      exercise in both rural and urban environments. By contrast, both rural and urban
      unpleasant scenes reduced the positive effects of exercise on self-esteem. The
      rural unpleasant scenes had the most dramatic effect, depressing the beneficial
      effects of exercise on three different measures of mood. It appears that threats
      to the countryside depicted in rural unpleasant scenes have a greater negative
      effect on mood than already urban unpleasant scenes. We conclude that green
      exercise has important public and environmental health consequences.

PMID- 16416751
TI  - Occurrence of Cryptosporidium and Giardia in irrigation water and its impact on
      the fresh produce industry.
AB  - In Mexico, relatively few studies have examined the presence of protozoan
      parasites from surface waters with irrigation and wash-water applications in the
      fresh produce industry. In this study, the presence of Cryptosporidium oocysts
      and Giardia cysts in surface water for irrigation, washing and disinfecting
      applications was evaluated. In addition, the occurrence of Cryptosporidium
      oocysts and Giardia cysts was determined in wash-water tanks at selected
      packinghouses. The occurrence of both Cryptosporidium and Giardia was determined
      by an immunofluorescent technique. Forty-eight percent of the surface water
      samples tested positive for Cryptosporidium oocysts and 50% tested positive for
      Giardia cysts. Concentration ranges for Cryptosporidium oocysts and Giardia cysts
      were 17-200 and 17-1633 per 100 litres, respectively. Sixteen percent of the wash
      water tanks tested positive for Cryptosporidium oocysts and 83% were positive for
      Giardia cysts with concentrations ranging from 1-133 oocysts and 100-533 cysts
      per 100 litres, respectively. The presence of protozoan parasites in surface
      water for irrigation and packinghouse operations suggests that there may be a
      risk of contamination of fresh produce as protozoan oocysts/cysts might come in
      contact with and attach to crop surfaces posing a risk of infection to consumers
      who eat these products.

PMID- 16416752
TI  - Synoptic weather patterns and modification of the association between air
      pollution and human mortality.
AB  - To assess whether meteorological conditions modify the relationship between short
      term exposure to ambient air pollution and mortality, an examination of air
      pollution and human mortality associations (ecologic) using hybrid spatial
      synoptic classification procedures was conducted. Concentrations of air
      pollutants and human mortality from all non-accidental and cardiorespiratory
      causes were examined according to typical winter and summer synoptic
      climatologies in Toronto, Canada, between 1981 and 1999. Air masses were derived
      using a hybrid spatial synoptic classification procedure associating each day
      over the 19-year period with one of six different typical weather types, or a
      transition between two weather types. Generalized linear models (GLMs) were used
      to assess the risk of mortality from air pollution within specific air mass type
      subsets. Mortality follows a distinct seasonal pattern with a maximum in winter
      and a minimum in summer. Average air pollution concentrations were similar in
      both seasons with the exception of elevated sulfur dioxide levels in winter and
      elevated ozone levels in summer. Subtle changes in meteorological composition can
      alter the strength of pollutant associations with health outcomes, especially in
      the summer season. Although there does not appear to be any systematic patterning
      of modification, variation in pollutant concentrations seems dependent on the
      type of synoptic category present.

PMID- 16416754
TI  - General health status of residents of the Selebi Phikwe Ni-Cu mine area,
      Botswana.
AB  - Residents of the Selebi Phikwe area, Botswana where nickel-copper (Ni-Cu) is
      being exploited often exhibit symptoms of varied degrees of ailments, sicknesses
      and diseases. A need to investigate their general health status was therefore
      eminent. Primary data was obtained by means of a questionnaire and structured
      interviews conducted with individuals, health service providers, business
      enterprises and educational Institutions. The generated data revealed common
      ailments, sicknesses and diseases in the area with the four most frequent health
      complaints being frequent coughing headaches, influenza/common colds and rampant
      chest pains. Research findings indicated that residents had respiratory tract
      related problems, suspected to be linked to the effects of air pollution caused
      by the emission of sulphur dioxide (SO2) from mining and smelting activities.
      Residents were frequently in contact with SO2 and related gases and fumes,
      mineral and silica dust generated from the mining processes. No clearly
      demarcating differences were noticed in the health status of residents living in
      the control site from those in the main study area. However, sites most affected
      were those close to where Ni-Cu is exploited. Environmental factors resulting
      from mining and smelting activities, among others, could be contributory to the
      negative health effects occurring at Selebi Phikwe.

PMID- 16416753
TI  - Acceptability of solar disinfection of drinking water treatment in Kathmandu
      Valley, Nepal.
AB  - This research examines the acceptability of solar disinfection of drinking water
      (SODIS) in a village in Kathmandu Valley, Nepal, using constructs from the Health
      Belief Model as a framework to identify local understandings of water, sanitation
      and health issues. There has been no published research on the acceptability of
      SODIS in household testing in Nepal. Understanding the context of water and water
      purity in Nepalese villages is essential to identify culturally appropriate
      interventions to improve the quality of drinking water and health. Forty
      households from the village census list were randomly selected and the senior
      woman in each household was asked to participate. Baseline data on water sources
      and behaviors were collected in March 2002, followed by training in SODIS. Follow
      up data were collected in June and July 2002. Only 9% of households routinely
      adopted SODIS. Participants mentioned the benefit of treating water to reduce
      stomach ailments, but this did not outweigh the perceived barriers of heavy
      domestic and agricultural workloads, other cultural barriers, uncertainty about
      the necessity of treating the water, and lack of knowledge that untreated
      drinking water causes diarrhea. Strategies for developing safe water systems must
      include public health education about waterborne diseases, source water
      protection, and a motivational component to achieve implementation and sustained
      use. In addition, other options for disinfecting water should be provided, given
      the women's work constraints and low level of formal education.

PMID- 16416755
TI  - Association between ambient air pollution and health-related quality of life in
      Japan: ecological study.
AB  - To assess the association between air pollution and health-related quality of
      life (HRQOL), we performed an ecological study by a two-stage stratified random
      sampling of the Japanese general population. A total of 3395 subjects, aged 16
      and older, filled out questionnaires, including the Medical Outcomes Study Short
      Form-36 Health Survey (SF-36). Air pollutants examined in this study were
      nitrogen oxides (NOx) and suspended particulate matter (SPM). We used analysis of
      covariance to estimate the mean differences for each SF-36 domain among four
      groups categorized according to concentrations of air pollutants to which they
      were exposed. We observed a significant linear trend of a lower 'vitality' domain
      score in the SF-36 in groups exposed to higher concentrations of NOx (p = 0.013).
      The results of the present study are important for, and needed by, public health
      policy makers, because assessing the health effects of air pollution by measuring
      the HRQOL would provide a new method for formulating air pollution policies.

PMID- 16416756
TI  - First report of cryptosporidiosis in paediatric patients in Swaziland.
AB  - Diarrhoeal disease is a significant cause of morbidity and mortality in many
      African countries, especially among the immunocompromised and the under five
      population. Over the last decade, the protozoan parasite Cryptosporidum spp. has
      been shown to be a significant cause of gastro-enetritis in the immunocompetent
      and immunocompromised in both the developed and developing world. This study
      reports the first finding of Cryptosporidum spp. oocysts in 2 of 48 (4.2%) faecal
      samples obtained from Swazi paediatric outpatients (two year old male and three
      year old female), presenting with diarrhoea at Mbabane Government Hospital
      between the months July-August 2003. Oocysts were detected using a standard anti
      Cryptosporidium immunofluorescence and nuclear staining technique (after formal
      ether concentration). Oocysts ranged in size from 4-6 microm with between 1-4
      oocysts per field of view (x 400). The precise species was not determined.
      Further studies are required to determine the public health significance of
      Cryptospoirdium in Swaziland.

PMID- 16416757
TI  - Cost effectiveness of long-acting risperidone: what can pharmacoeconomic models
      teach us?

PMID- 16416758
TI  - Pharmacoeconomics of long-acting risperidone: results and validity of cost
      effectiveness models.
AB  - Relapse is the primary cost driver in schizophrenia and is closely related to
      levels of adherence (compliance) with therapy. Both atypical antipsychotic agents
      and depot preparations have been shown to be useful in improving therapeutic
      adherence compared with oral conventional antipsychotic agents. Long-acting
      risperidone is a new formulation of an atypical antipsychotic agent that combines
      the pharmacological advantages of the atypical drugs with those of its mode of
      administration. The likelihood of improved compliance compared with existing
      treatment regimens implies that the higher acquisition costs would be offset by
      reduced rates of relapse. Economic models, which represent the health and
      economic outcomes of patients or populations under a variety of scenarios, are
      used to evaluate the economic implications of schizophrenia treatment. These
      models need to reflect clinical reality while simultaneously remaining as simple
      as possible. The assumptions and results need to be made transparent; data
      quality must be described explicitly; areas of uncertainty must be
      comprehensively explored through sensitivity analysis; and individual models must
      be validated, for example by comparing them with others in the therapeutic area.
      In this article, cost-effectiveness models of long-acting risperidone developed
      for different countries are discussed in terms of design, data sources and
      robustness, and the implications of the results for the treatment of
      schizophrenia are also reviewed. A discrete event simulation (DES) model that was
      developed using UK cost and treatment assumptions, in order to provide a 'proof
      of concept', is described. Country-specific models forthe United States, Canada,
      Germany, the Netherlands, France, Belgium, Italy and Portugal, using either DES
      or decision analytical structures, are then discussed. Comprehensive sensitivity
      analyses were conducted to assess the robustness of the results. In each case,
      long-acting risperidone produced additional clinical benefit and cost savings
      compared with other treatment strategies, despite significant variations in cost
      effectiveness and therapeutic approaches. In particular, improved adherence
      arising through the use of long-acting risperidone provides a cost-effective
      strategy for treating patients with schizophrenia, irrespective of the country
      analysed. The information generated in this analysis therefore provides one
      potential method for improving resource allocation and reducing the health burden
      related to schizophrenia.

PMID- 16416759
TI  - Modelling the treated course of schizophrenia: development of a discrete event
      simulation model.
AB  - In schizophrenia, modelling techniques may be needed to estimate the long-term
      costs and effects of new interventions. However, it seems that a simple direct
      link between symptoms and costs does not exist. Decisions about whether a patient
      will be hospitalized or admitted to a different healthcare setting are based not
      only on symptoms but also on social and environmental factors. This paper
      describes the development of a model to assess the dependencies between a broad
      range of parameters in the treatment of schizophrenia. In particular, the model
      attempts to incorporate social and environmental factors into the decision-making
      process for the prescription of new drugs to patients. The model was used to
      analyse the potential benefits of improving compliance with medication by 20% in
      patients in the UK. A discrete event simulation (DES) model was developed, to
      describe a cohort of schizophrenia patients with multiple psychotic episodes. The
      model takes into account the patient's sex, disease severity, potential risk of
      harm to self and society, and social and environmental factors. Other variables
      that change over time include the number of psychiatric consultations, the
      presence of psychotic episodes, symptoms, treatments, compliance, side-effects,
      the lack of ability to take care of him/herself, care setting and risk of harm.
      Outcomes are costs, psychotic episodes and symptoms. Univariate and multivariate
      sensitivity analyses were performed. Direct medical costs were considered (year
      of costing 2002), applying a 6.0% discount rate for costs and a 1.5% discount
      rate for outcome. The timeframe of the model is 5 years. When 50% of the
      decisions about the patient care setting are based on symptoms, a 20% increase in
      compliance was estimated to save 16,147 pounds and to avoid 0.55 psychotic
      episodes per patient over 5 years. Sensitivity analysis showed that the costs
      savings associated with increased compliance are robust over a range of
      variations in parameters. DES offers a flexible structure for modelling a
      disease, taking into account how a patient's history affects the course of the
      disease over time. This approach is particularly pertinent to schizophrenia, in
      which treatment decisions are complex. The model shows that better compliance
      increases the time between relapses, decreases the symptom score, and reduces the
      requirement for treatment in an intensive patient care setting, leading to cost
      savings. The extent of the cost savings depends on the relative importance of
      symptoms and of social and environmental factors in these decisions.

PMID- 16416760
TI  - Long-acting risperidone compared with oral olanzapine and haloperidol depot in
      schizophrenia: a Belgian cost-effectiveness analysis.
AB  - Patients with schizophrenia suffer numerous relapses and rehospitalizations that
      are associated with high direct and indirect medical expense. Suboptimal
      therapeutic efficacy and, in particular, problems with compliance are major
      factors leading to relapse. Atypical antipsychotic agents offer improved efficacy
      and a lower rate of extrapyramidal adverse effects compared with conventional
      antipsychotic drugs. Long-acting intramuscular risperidone combines these
      benefits with improvements in compliance associated with depot injections. To
      assist decision making regarding the place of long-acting risperidone in therapy,
      a cost-effectiveness analysis of strategies involving first-line treatment with
      long-acting risperidone, oral olanzapine or depot haloperidol was performed from
      the perspective of the Belgian healthcare system. A decision tree model was
      created to compare the cost effectiveness of three first-line treatment
      strategies in a sample of young schizophrenic patients who had been treated for 1
      year and whose disease had not been diagnosed for longer than 5 years. The model
      used a time horizon of 2 years, with health state transition probabilities,
      resource use and cost estimates derived from clinical trials, expert opinion and
      published prices. The four health states in the model were derived from an
      analysis of the literature. The principal efficacy measure was the proportion of
      patients successfully treated, defined as those who responded to initial
      treatment and who had none to two episodes of clinical deterioration without
      needing a change of treatment over the 2-year period. Comprehensive sensitivity
      analysis was carried out to test the robustness of the model. A greater
      proportion of patients were successfully treated with long-acting risperidone
      (82.7%) for 2 years, compared with those treated with olanzapine (74.8%) or
      haloperidol (57.3%). Total mean costs per patient over 2 years were 16,406 Euro
      with long-acting risperidone, 17,074 Euro with olanzapine and 21,779 Euro with
      haloperidol (year of costing 2003). The mean cost-effectiveness ratios were
      19,839 Euro, 22,826 Euro and 38,008 Euro per successfully treated patient for
      long-acting risperidone, olanzapine and haloperidol, respectively. Results of the
      sensitivity analysis confirmed that the results were robust to a wide variation
      of different input variables (effectiveness, dosing distribution, patient status
      according to healthcare system). Long-acting risperidone was the dominant
      strategy, being both more effective and less costly than either oral olanzapine
      or depot haloperidol. Long-acting risperidone appears to represent a favourable
      first-line strategy for patients with schizophrenia requiring long-term
      maintenance treatment.

PMID- 16416761
TI  - Costs and effects of long-acting risperidone compared with oral atypical and
      conventional depot formulations in Germany.
AB  - Schizophrenia is one of the most expensive psychiatric conditions because of high
      direct and indirect costs associated with the nature of the illness, its
      resistance to treatment and the consequences of relapse. Long-acting risperidone
      is a new formulation of an atypical antipsychotic drug that also offers the
      improvements in compliance associated with haloperidol depot. The aim of this
      simulation study was to compare the benefits and costs of three pharmacological
      treatment strategies comprising first-line treatment with long-acting risperidone
      injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5
      year period in Germany. A discrete event simulation model was developed to
      compare three treatment scenarios from the perspective of major third-party
      payers (sickness funds and social security 'Sozialversicherung'). The scenarios
      comprised first-line treatment with haloperidol depot (scenario 1), long-acting
      risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or
      third-line options were allowed when side-effects occurred or a patient suffered
      more than a fixed number of relapses. The model accounted for fixed patient
      characteristics, and on the basis of these, simulated patient histories according
      to several time-dependent variables. The time horizon for this model was limited
      to 5 years, and in accordance with German guidelines, costs and effects were
      discounted by between 3 and 10%. Direct costs included medication, type of
      physician visits and treatment location. Indirect costs were not included.
      Information on treatment alternatives, transition probabilities, model structure
      and healthcare utilization were derived from the literature and an expert panel.
      Outcomes were expressed in terms of the number and duration of psychotic
      episodes, cumulative symptom scores, costs, and quality-adjusted life-years
      (QALY). Univariate sensitivity analyses were carried out, as were subgroup
      analyses based on disease severity and for patients at high risk of being non
      compliant. The long-acting risperidone strategy was calculated to avoid 0.23 and
      0.33 relapses per patient, decrease the cumulative symptom score by 25 and 33
      points, and decrease the costs by 2017 Euro and 6096 Euro per patient (1608 Euro
      and 5422 Euro discounted), compared with the haloperidol depot and olanzapine
      strategies, respectively, over a 5-year period (year of costing 2004). Among high
      risk non-compliant patients, long-acting risperidone was estimated to avoid 0.23
      and 0.47 relapses and save 4822 Euro and 10,646 Euro per patient (4107 Euro and
      9490 Euro discounted), compared with the haloperidol depot and olanzapine
      strategies, respectively. Sensitivity analyses showed that the results were
      robust and mainly sensitive to changes in the reported relative effectiveness of
      atypical and conventional formulations for preventing symptom recurrence, and in
      the relative compliance with oral and long-acting formulations. In this model,
      long-acting risperidone is a dominant strategy compared with a haloperidol depot
      or oral atypical antipsychotic agent, being both more effective and less costly
      over a 5-year period. Results for long-acting risperidone are even more
      favourable among patients at high risk of being noncompliant or with more severe
      disease.

PMID- 16416762
TI  - Modelling the impact of compliance on the costs and effects of long-acting
      risperidone in Canada.
AB  - Schizophrenia is a chronic, relapsing disease that requires more healthcare
      resources to manage than any other single psychiatric illness. The main cost of
      treatment is hospitalization as a result of the exacerbation of symptoms often
      caused by poor compliance. Although the costs of hospitalization and relapse have
      been well documented, the differential effects of various medications on
      healthcare expenditure are still being determined. The aim of the present study
      was to estimate the cost effectiveness of long-acting risperidone in the
      treatment of high-risk, non-compliant patients with schizophrenia over a 5-year
      period in Canada. A discrete event model was developed comparing three scenarios,
      each with a different starting treatment: haloperidol depot, long-acting
      risperidone or oral risperidone. Second and third-line treatment options were
      olanzapine and clozapine, respectively, for all three scenarios. On the basis of
      3000 simulated patient characteristics, the model generated individual patient
      histories. Outcomes included the number and duration of psychotic episodes, the
      cumulative Positive and Negative Syndrome Scale (PANSS) score and direct medical
      costs. The time horizon of the model was 5 years and a 5% discount rate was used
      for costs and effects. The perspective of the model was that of the Canadian
      healthcare system. After 5 years, treatment with long-acting risperidone saved
      Canada dollars 6908 and Canada dollars 13,130 (discounted) and avoided 0.28 and
      0.54 relapses per patient, compared with haloperidol depot and oral risperidone,
      respectively. In this model, initiating treatment of high-risk, non-compliant
      patients with schizophrenia with long-acting risperidone was the dominant
      strategy. With long-acting risperidone, direct costs were lower and clinical
      effectiveness was greater, compared with haloperidol depot or oral risperidone,
      during years 4 and 5.

PMID- 16416764
TI  - [Guidelines on genetic research and genetic testing].

PMID- 16416765
TI  - [Ethical, legal and social implication of genetic testing].

PMID- 16416763
TI  - Cost effectiveness of long-acting risperidone injection versus alternative
      antipsychotic agents in patients with schizophrenia in the USA.
AB  - The availability of long-acting risperidone injection may increase adherence and
      lead to improved clinical and economic outcomes for individuals with
      schizophrenia. The objective of this study was to assess the cost effectiveness
      of long-acting risperidone, oral risperidone, olanzapine, quetiapine,
      ziprasidone, aripiprazole, and haloperidol depot in patients with schizophrenia
      over 1 year from a healthcare system perspective. Published medical literature,
      unpublished data from clinical trials and a consumer health database, and a
      clinical expert panel were utilized to populate a decision analytical model
      comparing the seven treatment alternatives. The model captured rates of patient
      compliance, the rates, frequency and duration of relapse, incidence of adverse
      events, and healthcare resource utilization and associated costs. Primary
      outcomes were expressed in terms of percentage of patients relapsing per year,
      number of relapse days per year (number and duration of relapses per patient per
      year), and total direct 2003 medical cost per patient per year. On the basis of
      model projections, the proportions of patients experiencing a relapse requiring
      hospitalization in 1 year were 66% for haloperidol depot, 41% for oral
      risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 26% for
      long-acting risperidone, whereas the proportions of patients with an exacerbation
      not requiring hospitalization were 60% for haloperidol depot, 37% for oral
      risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 24% for
      long-acting risperidone. The mean number of days of relapse requiring
      hospitalization per patient per year were 28 for haloperidol depot, 18 for oral
      risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 11 for
      long-acting risperidone, whereas the mean number of days of exacerbation not
      requiring hospitalization were eight for haloperidol depot, five for oral
      risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and three for
      long-acting risperidone. This would translate into direct medical cost savings
      with long-acting risperidone compared with oral risperidone, olanzapine,
      quetiapine, ziprasidone, aripiprazole, and haloperidol depot of US dollars 161,
      1425, 508, 259, 1068, and 8224, respectively. These findings were supported by
      sensitivity analyses. The utilization of long-acting risperidone is predicted to
      result in better clinical outcomes and lower total healthcare costs than its
      comparators, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole,
      and haloperidol depot. Long-acting risperidone may therefore be a cost saving
      therapeutic option for patients with schizophrenia.

PMID- 16416766
TI  - [Currents state and future prospects of certified genetic counselor in Japan].

PMID- 16416768
TI  - [BioBank Japan project].

PMID- 16416767
TI  - [International HapMap project].

PMID- 16416769
TI  - [Cancer genomics in post-sequence era].

PMID- 16416770
TI  - [Pharmacogenomics: current status and future prospectives].

PMID- 16416771
TI  - [Single gene disorder].

PMID- 16416772
TI  - [Chromosomal abnormalities and genomic disorders].

PMID- 16416773
TI  - [Multifactorial disease].

PMID- 16416774
TI  - [Mitochondrial genetic diseases].

PMID- 16416775
TI  - [Somatic mosaicism in genetic diseases].

PMID- 16416776
TI  - [Genetic test for symptomatic patients].

PMID- 16416777
TI  - [Presymptomatic testing and predictive testing].

PMID- 16416778
TI  - [Carrier testing].

PMID- 16416779
TI  - [Neonatal screening].

PMID- 16416780
TI  - [Prenatal diagnosis and screening].

PMID- 16416781
TI  - [Preimplantation genetic diagnosis].

PMID- 16416782
TI  - [Advances in biotechnologies for molecular diagnostics].

PMID- 16416783
TI  - [Standardization and quality control in gene--based testing].

PMID- 16416784
TI  - [Methods for the specimen preparation for molecular diagnostic tests].

PMID- 16416785
TI  - [Southern hybridization, northern hybridization].

PMID- 16416786
TI  - [Gene amplification method].

PMID- 16416787
TI  - [In situ hybridization: a molecular histochemical technique to analyze the
      expression of specific RNA in cells].

PMID- 16416788
TI  - [Cytogenetic analysis (chromosome analysis and FISH analysis)].

PMID- 16416789
TI  - [Microarray CGH].

PMID- 16416790
TI  - [Functional genomic analysis with microarray technology].

PMID- 16416791
TI  - [DNA methylation analysis].

PMID- 16416792
TI  - [Genetic testing for neuromuscular disorders].

PMID- 16416793
TI  - [Genetic testing and gene-based testing for familial tumor].

PMID- 16416794
TI  - [Molecular genetics of cardiovascular diseases].

PMID- 16416795
TI  - [Genetic testing and gene-based testing for endocrine disorders].

PMID- 16416796
TI  - [Gene-based testing for respiratory disease].

PMID- 16416797
TI  - [Genetic testing and gene--based testing for colorectal cancer].

PMID- 16416798
TI  - [Genetic testing and gene-based testing for inherited renal and vascular
      diseases].

PMID- 16416799
TI  - [Molecular genetics of rheumatic diseases].

PMID- 16416800
TI  - [Genetic testing and gene-based testing forAllergic disorders].

PMID- 16416801
TI  - [Genetic testing and gene-based testing for hematological disorder].

PMID- 16416802
TI  - [Molecular diagnosis of malignant lymphoma].

PMID- 16416803
TI  - [Genetic testing and gene-based testing for mental disorders].

PMID- 16416804
TI  - [Genetic diagnosis of deafness].

PMID- 16416805
TI  - [Molecular genetic analysis of inherited ocular diseases].

PMID- 16416806
TI  - [Inborn errors of metabolism].

PMID- 16416807
TI  - [Genetic testing and gene-based testing of life-style related disease].

PMID- 16416808
TI  - [Genetic testing and gene-based testing for obesity].

PMID- 16416809
TI  - [Genetic testing and gene-based testing for hyperuricemia and gout].

PMID- 16416810
TI  - [Genetic testing and gene-based testing for hypertension].

PMID- 16416811
TI  - [Genetic testing and gene-based testing for type 2 diabetes].

PMID- 16416812
TI  - [Genetic testing and gene-based testing for hyperlipidemia and lipid metabolism
      disorders].

PMID- 16416813
TI  - [Diagnosis of infectious diseases by nucleic acid amplifications].

PMID- 16416814
TI  - [Nucleic acid-based testing for hepatitis B viruss infectious disease].

PMID- 16416815
TI  - [Nucleic acid-based testing for hepatitis C virus infection].

PMID- 16416816
TI  - [Nucleic acid -based testing for HIV infection].

PMID- 16416817
TI  - [Nucleic acid-based testing for cytomegalovirus infection].

PMID- 16416818
TI  - [Gene-based testing of Mycobacterium tuberculosis].

PMID- 16416819
TI  - [Genetic diagnosis of H. pylori infection].

PMID- 16416820
TI  - [Detection of SARS coronavirus RNA].

PMID- 16416821
TI  - [Sepsis--diagnostic approaches for bacterial sepsis].

PMID- 16416822
TI  - [Nucleic acid-based testing for methicillin-resistant Staphylococcus aureus
      infection].

PMID- 16416823
TI  - [Nucleic acid-based testing for vancomycin-resistant enterococcal infection].

PMID- 16416824
TI  - [Forensic medicine and genetic testing].

PMID- 16416825
TI  - [Organ transplant and genetic testing].

PMID- 16416827
TI  - [Positional cloning of disease gene].

PMID- 16416826
TI  - [Analysis of the genes mediating antibiotic resistance in causative
      microorganisms of respiratory tract infections].

PMID- 16416828
TI  - [Genetic testing for Marfan syndrome].

PMID- 16416829
TI  - [Molecular diagnosis of multiple malformation syndrome].

PMID- 16416830
TI  - [Susceptibility genes for schizophrenia].

PMID- 16416831
TI  - [Gene analysis of blood groups].

PMID- 16416832
TI  - [Cytochrome P450 2C19 genotype -based second line therapy with amoxicillin and
      lansoprazole after failure of initial helicobacter pylori eradication therapy].

PMID- 16416833
TI  - [TSLC1/IGSF4, a potential target of suppression for the invasion and metastasis
      of human cancer].

PMID- 16416834
TI  - [Identification of asporin, a susceptibility gene for osteoarthritis].

PMID- 16416835
TI  - [Genetic analyses of morphine sensitivity].

PMID- 16416836
TI  - [Current status and future prospective of gene therapy].

PMID- 16416837
TI  - [Guidelines on clinical research of gene therapy].

PMID- 16416838
TI  - [Bioethics in gene diagnosis and gene therapy].

PMID- 16416839
TI  - [Methods of gene transfer].

PMID- 16416840
TI  - [Strategies for gene therapy].

PMID- 16416841
TI  - [Translational research in gene therapy].

PMID- 16416843
TI  - [Gene therapy for lung cancer].

PMID- 16416842
TI  - [Current status of gene therapy in oversea countries].

PMID- 16416844
TI  - [Gene therapy for hepatocellular carcinoma].

PMID- 16416845
TI  - [Gene therapy for esophageal cancer].

PMID- 16416846
TI  - [Gene therapy for breast cancer].

PMID- 16416847
TI  - [Gene therapy of cancer: renal cell carcinoma].

PMID- 16416848
TI  - [Gene therapy for colon cancer].

PMID- 16416849
TI  - [Gene therapy for liver metastasis of colon cancer].

PMID- 16416850
TI  - [Prostate cancer gene therapy].

PMID- 16416851
TI  - [Gene therapies for bladder cancer].

PMID- 16416852
TI  - [Gene therapy for ovarian cancer].

PMID- 16416853
TI  - [Gene therapy for glioma].

PMID- 16416854
TI  - [Gene therapy for patients with malignant melanoma].

PMID- 16416855
TI  - [Gene therapy for hematopoietic malignancy].

PMID- 16416856
TI  - [Future view of gene therapy in cardiovascular field].

PMID- 16416857
TI  - [Gene therapy for peripheral arterial disease].

PMID- 16416858
TI  - [Therapeutic angiogenesis for ischemic heart disease induced by gene transfer].

PMID- 16416859
TI  - [Gene therapy in congestive heart failure].

PMID- 16416860
TI  - [Overview of gene transfer in the area of respiratory diseases].

PMID- 16416861
TI  - [Cystic fibrosis and gene therapy].

PMID- 16416862
TI  - [Gene therapy for respiratory tract infection].

PMID- 16416863
TI  - [Gene therapy for Parkinson's disease].

PMID- 16416864
TI  - [Molecular therapy for duchenne muscular dystrophy].

PMID- 16416865
TI  - [Gene therapy for stroke].

PMID- 16416866
TI  - [Gene therapy for leukemia].

PMID- 16416867
TI  - [Gene therapy for primary immunodeficiency diseases].

PMID- 16416868
TI  - [Gene therapy for hemophilia].

PMID- 16416869
TI  - [Gene therapy for rheumatoid arthritis].

PMID- 16416870
TI  - [NFkappaB decoy DNA for treatment of atopic dermatitis].

PMID- 16416871
TI  - [Immunogene therapy against allergic asthma].

PMID- 16416872
TI  - [Gene therapy for lysosomal disorders].

PMID- 16416873
TI  - [Gene therapy for retinal disease].

PMID- 16416874
TI  - [Experimental gene therapy for Alzheimer's disease--animal models].

PMID- 16416875
TI  - [Gene therapy for diabetes mellitus].

PMID- 16416876
TI  - [Genetic, genomic and nucleic acid testing services provided by commercial
      laboratories].

PMID- 16416877
TI  - [Molecular mechanisms of kinetchore microtubule interaction].

PMID- 16416878
TI  - [Tumor suppression by cellular senescence: molecular link between aging and
      cancer].

PMID- 16416879
TI  - [New role of voltage sensor: voltage-regulated phosphatase recently identified
      from ascidian genome].

PMID- 16416880
TI  - [Establishment and progress of Sendai virus engineering].

PMID- 16416881
TI  - [Shoot branching and plant form].

PMID- 16416882
TI  - [tRNA shuttling between the nucleus and cytoplasm].

PMID- 16416883
TI  - [Role of RNA polymerase II in RNAi-dependent heterochromatin formation].

PMID- 16416884
TI  - [A whole genome cloning in the BGM vector].

PMID- 16416885
TI  - [Molecular machinery governing GABAergic neuron production in the cerebellum].

PMID- 16416886
TI  - Healthcare safety--what does managed care have to do with it?

PMID- 16416887
TI  - Measuring quality in nurse-managed centers using HEDIS measures.
AB  - Nurse-managed centers (NMCs) provide viable options for primary healthcare and
      contribute substantially to filling access gaps for vulnerable populations. The
      purposes of this paper are to (a) describe a pilot application and adaptation of
      eight Health Plan Employer Data and Information Set (HEDIS) measures to six NMCs,
      (b) report the findings from the quality assessments, and (c) compare findings to
      national HEDIS data. The eight quality assessment areas are asthma, cervical
      cancer screening, childhood immunizations, depression, diabetes, hypertension,
      mammography screening, and smoking cessation. The NMCs achieved or exceeded HEDIS
      50th percentile levels in a number of important clinical areas, but did not
      attain the 50th percentile level in others. Thus, HEDIS measures are relevant for
      the assessment of care quality and provide useful data for quality improvement in
      NMCs.

PMID- 16416889
TI  - Diffusion of information technology supporting the Institute of Medicine's
      quality chasm care aims.
AB  - This article examines the degree to which healthcare information technology (HIT)
      supporting the Institute of Medicine's (IOM) six care aims is utilized in the
      hospital setting and explores organizational factors associated with HIT use.
      Guided by the IOM's Crossing the quality chasm report and associated literature,
      27 applications and/or capabilities are classified according to one or more of
      the six care aims. A structured survey of Florida hospitals identified the use of
      HIT. Results suggest that, on average, hospitals have not yet embraced HIT to
      support the IOM's care aims and that associated organizational factors vary
      according to care aim.

PMID- 16416888
TI  - Development and implementation of an interdisciplinary plan of care.
AB  - In January 2002 Aurora Health Care Metro Region chartered an interdisciplinary
      team to develop a process and structure for patient-centered interdisciplinary
      care planning. This unique endeavor created a process that includes the patient,
      family, and all clinical disciplines involved in planning and providing care to
      patients from system point of entry throughout the entire acute care episode. The
      interdisciplinary plan of care (IPOC) demonstrates the integration of prioritized
      problems, outcomes, and measurement toward goal attainment. This article focuses
      on the journey of this team to the successful implementation of an IPOC.

PMID- 16416890
TI  - Palliative care as a quality improvement strategy for advanced, chronic illness.
AB  - Palliative care is medical care that provides relief from suffering and support
      for the best possible quality of life for patients facing advanced chronic
      illness and for their families. Healthcare organizations use palliative care to
      improve quality of care, because it is an effective approach to relieving pain,
      discomfort, and stress; improving patient and family satisfaction; improving
      continuity and reducing fragmentation of care delivery; and contributing to
      efficient and effective use of healthcare resources. As a result of these
      outcomes, palliative care programs help hospitals meet pain management and other
      quality accreditation standards. This article summarizes the data, provides case
      examples of the effect of palliative care, and identifies resources for
      implementing programs.

PMID- 16416892
TI  - The Kaiser Permanente FMEA model--simplified for healthcare personnel.

PMID- 16416891
TI  - Simulation of begin and end ages for mammography screening.
AB  - This article is designed to assist healthcare professionals in identifying begin
      and end ages for annual breast cancer mammography screening through the use of
      cost-effectiveness and computer modeling. With a limit of acceptability of
      $50,000 per life-year saved, the ages of screening were found to be 35 to 85. The
      present study identifies the end age for screening more clearly than currently
      available evidence while meeting the societal limits of $50,000 per life-year
      saved and equitable spending for the young and old alike.

PMID- 16416893
TI  - A comparison of the survival in feces and water of Escherichia coli O157:H7 grown
      under laboratory conditions or obtained from cattle feces.
AB  - Escherichia coli O157:H7 is an important foodborne pathogen that can cause
      hemorrhagic colitis and hemolytic uremic syndrome. Cattle feces and fecally
      contaminated water are important in the transmission of this organism on the
      farm. In this study, the survival of E. coli O157:H7 in feces and water was
      compared following passage through the animal digestive tract or preparation in
      the laboratory. Feces were collected from steers before and after oral
      inoculation with a marked strain of E. coli O157:H7. Fecal samples collected
      before cattle inoculation were subsequently inoculated with the marked strain of
      E. coli O157:H7 prepared in the laboratory. Subsamples were taken from both
      animal and laboratory-inoculated feces to inoculate 5-liter volumes of water. E.
      coli O157:H7 in feces survived up to 97 days, and survival was not affected by
      the method used to prepare the inoculating strain. E. coli O157:H7 survived up to
      109 days in water, and the bacteria collected from inoculated cattle were
      detected up to 10 weeks longer than the laboratory-prepared culture. This study
      suggests that pathogen survival in low-nutrient conditions may be enhanced by
      passage through the gastrointestinal tract.

PMID- 16416894
TI  - Inactivation of Escherichia coli (ATCC 4157) in diluted apple cider by dense
      phase carbon dioxide.
AB  - Dense-phase carbon dioxide (CO2) treatments in a continuous flow through system
      were applied to apple cider to inactivate Escherichia coli (ATCC 4157). A
      response surface design with factors of the CO2/product ratio (0, 70, and 140
      g/kg), temperature (25, 35, and 45 degrees C), and pressure (6.9, 27.6, and 48.3
      MPa) were used. E. coli was very sensitive to dense CO2 treatment, with a more
      than 6-log reduction in treatments containing 70 and 140 g/kg CO2, irrespective
      of temperature and pressure. The CO2/product ratio was the most important factor
      affecting inactivation rate of E. coli. No effect of temperature and pressure was
      detected because of high sensitivity of the cells to dense CO2. Dense CO2 could
      be an alternative pasteurization treatment for apple cider. Further studies
      dealing with the organoleptic quality of the product are needed.

PMID- 16416895
TI  - Survey of Japanese layer farms for Salmonella enteritidis with vaccination- and
      infection-specific antigens for egg yolk antibodies.
AB  - Japanese layer farms were surveyed for Salmonella Enteritidis vaccination and
      infection with specific antigens for egg yolk antibodies with the use of
      vaccination-specific antigen Salmonella Enteritidis FliC-specific 9-kDa
      polypeptide (SEP9) and infection-specific antigen deflagellated Salmonella
      Enteritidis whole cell (DEWC). The specific antibodies in eggs from 201
      commercial layer farms throughout Japan were surveyed. The percentages of farm
      flocks with a mean enzyme-linked immunosorbent assay (ELISA) titer of over 0.1
      were 56.2% (113 of 201) in DEWC-ELISA and 22.3% (45 of 201) in SEP9-ELISA. Flocks
      indicating high titers in SEP9-ELISA always showed high titers in DEWC-ELISA.
      Because both specific antibody titers of the vaccinated flocks monitored long
      term remained high throughout life, flocks with high titers of both ELISAs in
      this survey must be vaccinated. On the other hand, 34.3% (69 of 201) of flocks
      had high titers of DEWC-specific antibody alone. Because Salmonella Enteritidis
      infection induces the DEWC-specific antibody but not the SEP9-specific antibody,
      detecting only high ELISA titers of DEWC-specific antibody can be an effective
      monitoring tool for Salmonella Enteritidis exposure rather than vaccination.
      These results suggest that vaccination programs in Japanese layer farms would be
      insufficient to control Salmonella Enteritidis infection, and egg screening to
      detect specific antibodies would be valuable in obtaining the necessary
      information to control Salmonella Enteritidis infection.

PMID- 16416896
TI  - Antibiotic resistance of Campylobacter jejuni and Campylobacter coli isolated
      from hog, beef, and chicken carcass samples from provincially inspected abattoirs
      in Ontario.
AB  - Campylobacterjejuni is one of the most common causes of bacterial foodborne
      infection in the United States, and there are reports of resistance of
      Campylobacter spp. to antimicrobial agents used for the treatment of
      gastroenteritis. The purpose of this study was to determine the antimicrobial
      resistance patterns of Campylobacter spp. isolated from hog, beef, and chicken
      carcasses from provincially inspected abattoirs in Ontario. The agar dilution
      method was performed to measure antimicrobial resistance of the isolates.
      Antimicrobial resistance of Campylobacter isolates from hogs (n = 401), beef (n =
      21), and chicken (n = 435) to ampicillin, azithromycin, chloramphenicol,
      ciprofloxacin, clindamycin, erythromycin, gentamicin, nalidixic acid,
      streptomycin, and tetracycline was determined. Resistance of chicken, hog, and
      beef isolates was 14.3, 18.2, and 9.5% to ampicillin; 17.9, 67.3, and 38.1% to
      azithromycin; 0, 0.5, and 0% to chloramphenicol; 3.7, 1.2, and 0% to
      ciprofloxacin; 2.3, 46.6, and 4.8% to clindamycin; 6.7, 43.6, and 4.8% to
      erythromycin; 0.2, 0, and 0% to gentamicin; 5.1, 10.7, and 0% to nalidixic acid;
      13.6, 57.4, and 4.8% to streptomycin; and 52.6, 44.1, 42.9% to tetracycline,
      respectively. The hog isolates had the greatest resistance to seven of the ten
      antimicrobials tested. Results of this study confirm the existence of
      antimicrobial resistance of Campylobacter to various antimicrobial
      agents,especially ciprofloxacin and erythromycin, commonly used for treatment of
      campylobacteriosis in humans.

PMID- 16416897
TI  - Campylobacter contamination during poultry slaughter in Belgium.
AB  - The relation between internal carriage and surface contamination with
      thermophilic Campylobacter species in broilers was examined by molecular typing
      methods. Samples from 39 flocks were collected in three Belgian poultry
      slaughterhouses. From each flock, crop swabs before slaughter and intestines and
      neck skins during slaughter were collected. A total of 309 isolates were
      identified at species level and further characterized by flagellin gene A
      PCR/restriction fragment length polymorphism and pulsed-field gel
      electrophoresis. Isolates were identified as Campylobacter jejuni (90%),
      Campylobacter coli (8.7%), and Campylobacter lari (2.2%), and 27 genotypes could
      be distinguished by combining the two molecular methods. Seventy-two percent of
      the flocks arriving at the abattoir were colonized with campylobacters. After
      slaughter, 79% of the flocks had contaminated neck skins. In six flocks,
      genotypes isolated from the neck skins were also found in the alimentary tract
      from previously slaughtered flocks. Four of these flocks were initially free of
      Campylobacter. These four flocks might have had no contaminated carcasses after
      logistic slaughtering.

PMID- 16416898
TI  - Growth of Campylobacter in media supplemented with organic acids.
AB  - The growth of Campylobacter spp. in media supplemented with organic acids was
      examined. A Bioscreen C Microbiology Reader was used to measure growth of
      cultures incubated at 37 degrees C for 48 h in a tryptose-yeast extract basal
      broth medium and in basal broth supplemented with 10, 20, 30, 40, or 50 mM
      citric, fumaric, lactic, malic, or succinic acid. Growth of three of six isolates
      was significantly greater (P < or = 0.05) in media supplemented with 20 to 50 mM
      citric acid than in nonsupplemented media, growth of five of six isolates was
      significantly greater in media supplemented with 10 to 50 mM succinic acid than
      in nonsupplemented media, and growth of six of six isolates was significantly
      greater in media supplemented with 10 to 50 mM fumaric or malic acid or with 20
      to 50 mM lactic acid than in nonsupplemented media. Isolates were also cultured
      in basal media supplemented with a mixture of 10, 20, 30, 40, or 50 mM fumaric,
      malic, lactic, and succinic acids. Results indicated that the growth of all
      Campylobacter isolates was significantly greater in media supplemented with
      mixtures containing each of these organic acids at 10 to 40 mM than in
      nonsupplemented media. These findings indicate that in vitro growth of
      Campylobacter spp. may be significantly enhancedin media supplemented with
      organic acids that support the growth of these bacteria.

PMID- 16416899
TI  - Hot water postprocess pasteurization of cook-in-bag turkey breast treated with
      and without potassium lactate and sodium diacetate and acidified sodium chlorite
      for control of Listeria monocytogenes.
AB  - Surface pasteurization and food-grade chemicals were evaluated for the ability to
      control listeriae postprocess on cook-in-bag turkey breasts (CIBTB). Individual
      CIBTB were obtained directly from a commercial manufacturer and surface
      inoculated (20 ml) with a five-strain cocktail (ca. 7.0 log) of Listeria innocua.
      In each of two trials, the product was showered or submerged for up to 9 min with
      water heated to 190, 197, or 205 degrees F (ca. 87.8, 91.7, or 96.1 degrees C) in
      a commercial pasteurization tunnel. Surviving listeriae were recovered from CIBTB
      by rinsing and were then enumerated on modified Oxford agar plates following
      incubation at 37 degrees C for 48 h. As expected, higher water temperatures and
      longer residence times resulted in a greater reduction of L. innocua. A ca. 2.0
      log reduction was achieved within 3 min at 205 and 197 degrees F and within 7 min
      at 190 degrees E In related experiments, the following treatments were evaluated
      for control of Listeria monocytogenes on CIBTB: (i) a potassium lactate-sodium
      diacetate solution (1.54% potassium lactate and 0.11% sodium diacetate) added to
      the formulation in the mixer and 150 ppm of acidified sodium chlorite applied to
      the surface with a pipette, or (ii) a potassium lactate-sodium diacetate solution
      only, or (iii) no potassium lactate-sodium diacetate solution and no acidified
      sodium chlorite. Each CIBTB was inoculated (20 ml) with ca. 5 log CFU of a five
      strain mixture of L. monocytogenes and then vacuum sealed. In each of two trials,
      half of the CIBTB were exposed to 203 degrees F water for 3 min in a
      pasteurization tunnel, and the other half of the CIBTB were not; then, all CIBTB
      were stored at 4 degrees C for up to 60 days, and L. monocytogenes was enumerated
      by direct plating onto modified Oxford agar. Heating resulted in an initial
      reduction of ca. 2 log CFU of L. monocytogenes per CIBTB. For heated CIBTB, L.
      monocytogenes increased by ca. 2 log CFU per CIBTB in 28 (treatment 1), 28
      (treatment 2), and 14 (treatment 3) days. Thereafter, pathogen levels reached ca.
      7 log CFU per CIBTB in 45, 45, and 21 days for treatments 1, 2, and 3,
      respectively. In contrast, for nonheated CIBTB, L. monocytogenes levels increased
      from ca. 5 log CFU per CIBTB to ca. 7 log CFU per CIBTB in 28, 21, and 14 days
      for treatments 1, 2, and 3, respectively. Lastly, in each of three trials, we
      tested the effect of hot water (203 degrees F for 3 min) postprocess
      pasteurization of inoculated CIBTB on the lethality of L. monocytogenes and
      validated that it resulted in a 1.8-log reduction in pathogen levels.
      Collectively, these data establish that hot water postprocess pasteurization
      alone is effective in reducing L. monocytogenes on the surface of CIBTB. However,
      as used in this study, the potassium lactate-sodium diacetate solution and
      acidified sodium chlorite were only somewhat effective at controlling the
      subsequent outgrowth of this pathogen during refrigerated storage.

PMID- 16416900
TI  - Combining organic acid treatment with steam pasteurization to eliminate Listeria
      monocytogenes on fully cooked frankfurters.
AB  - An organic acid solution of 2% acetic, 1% lactic, 0.1% propionic, and 0.1%
      benzoic acids was combined with steam surface pasteurization to treat
      frankfurters during vacuum packaging to eliminate potential postcook
      contamination with Listeria monocytogenes. The thermal lethality of L.
      monocytogenes from steam was evaluated at an inoculation concentration of 1 to 6
      log CFU/cm2. About 3-log reductions of L. monocytogenes were achieved when
      frankfurters were treated by steam for 1.5 s. Combining organic acid treatment
      with steam pasteurization further inhibited the growth of surviving L.
      monocytogenes cells for 19 and 14 weeks when the packaged frankfurters were
      stored at 4 and 7 degrees C, respectively. The results from this study provide
      meat processors with useful information for controlling L. monocytogenes on ready
      to-eat meats.

PMID- 16416901
TI  - Post process control of Listeria monocytogenes on commercial frankfurters
      formulated with and without antimicrobials and stored at 10 degrees C.
AB  - The antilisterial effect of postprocess antimicrobial treatments on commercially
      manufactured frankfurters formulated with and without a 1.5% potassium lactate
      0.05% sodium diacetate combination was evaluated. Frankfurters were inoculated
      (ca. 3 to 4 log CFU/cm2) with 10-strain composite Listeria monocytogenes cultures
      originating from different sources. The inocula evaluated were cells grown
      planktonically in tryptic soy broth plus 0.6% yeast extract (30 degrees C, 24 h)
      or in a smoked sausage homogenate (15 degrees C, 7 days) and cells that had been
      removed from stainless steel coupons immersed in an inoculated smoked sausage
      homogenate (15 degrees C, 7 days). Inoculated frankfurters were dipped (2 min, 25
      +/- 2 degrees C) in acetic acid (AA; 2.5%), lactic acid (LA; 2.5%), potassium
      benzoate (PB; 5%), or Nisaplin (commercial form of nisin; 0.5%, equivalent to
      5,000 IU/ml of nisin) solutions, or in Nisaplin followed by AA, LA, or PB, and
      were subsequently vacuum packaged and stored for 48 days at 10 degrees C. In
      addition to microbiological analyses, sensory evaluations were performed with
      uninoculated samples that had been treated with AA, LA, or PB for 2 min. Initial
      L. monocytogenes populations were reduced by 1.0 to 1.8 log CFU/cm2 following
      treatment with AA, LA, or PB solutions, and treatments that included Nisaplin
      reduced initial levels by 2.4 to >3.8 log CFU/ cm2. All postprocessing treatments
      resulted in some inhibition of L. monocytogenes during the initial stages of
      storage of frankfurters that were not formulated with potassium lactate-sodium
      diacetate; however, in all cases, significant (P < 0.05) growth occurred by the
      end of storage. The dipping of products formulated with potassium lactate-sodium
      diacetate in AA or LA alone--or in Nisaplin followed by AA, LA, or PB-increased
      lag-phase durations and lowered the maximum specific growth rates of the
      pathogen. Moreover, depending on the origin of the inoculum, this dipping of
      products led to listericidal effects. In general, differences in growth kinetics
      were obtained for the three inocula that were used to contaminate the
      frankfurters. Possible reasons for these differences include the presence of
      stress-adapted subpopulations and the inhibition of the growth of the pathogen
      due to high levels of spoilage microflora. The dipping of frankfurters in AA, LA,
      or PB did not (P > 0.05) affect the sensory attributes of the product when
      compared to the control samples. The data generated in this study may be useful
      to U.S. ready-to-eat meat processors in their efforts to comply with regulatory
      requirements.

PMID- 16416902
TI  - A predictive model for the effect of temperature and predrying treatments in
      reducing Listeria monocytogenes populations during drying of beef jerky.
AB  - The objective of this study was to model the effect of drying temperatures (52,
      57, and 63 degrees C) and predrying treatments on the inactivation of Listeria
      monocytogenes on beef jerky. Before drying, beef slices were inoculated with a 10
      strain composite of L. monocytogenes and then treated with the following: (i)
      nothing (C), (ii) traditional marinade (M), or (iii) dipping in 5% acetic acid
      solution for 10 min, followed by M (AM). In addition, sequential stresses
      (exposure to 10% NaCl, followed by an adjustment of the pH to 5.0 and,
      subsequently, a water bath at 45 degrees C) were applied to the inocula before
      beef contamination and drying at 63 degrees C. Surviving L. monocytogenes were
      determined on tryptic soy agar plus 0.6% yeast extract (TSAYE) and on PALCAM agar
      at 0, 2, 4, 6, 8, and 10 h during drying. Data were modeled by a linear
      regression (treatment AM) and a logistic-based equation capable of fitting
      biphasic inactivation curves without initial shoulder (treatments C and M). The
      total log reductions expressed as the CFU per square centimeter of L.
      monocytogenes (3.9 to 5.1) for the samples treated with M (3.5 to 5.4) when
      compared with C were similar, whereas AM-treated samples had higher (6.1 to 6.8)
      reductions. All survival curves were characterized by an initial rapid decrease
      in populations within the first 2 h, which was followed by a secondary death
      phase at a lower rate. No significant (P > or = 0.05) differences in inactivation
      were observed due to drying temperatures in the range (52 to 63 degrees C)
      tested. Inactivation differences between recovered counts of stressed and
      unstressed cells were significant (P < 0.05) in PALCAM but not in TSAYE. The
      acidified predrying treatment (AM) had higher pathogen inactivation during drying
      than other treatments, regardless of drying temperature. The models developed may
      be useful in designing effective drying processes for beef jerky.

PMID- 16416903
TI  - Cross-contamination between processing equipment and deli meats by Listeria
      monocytogenes.
AB  - Contamination of luncheon meats by Listeria monocytogenes has resulted in
      outbreaks of listeriosis and major product recalls. Listeriae can survive on
      processing equipment such as meat slicers which serve as a potential
      contamination source. This study was conducted to determine (i) the dynamics of
      cross-contamination of L. monocytogenes from a commercial slicer and associated
      equipment onto sliced meat products, (ii) the influence of sample size on the
      efficacy of the BAX-PCR and U.S. Department of Agriculture-Food Safety and
      Inspection Service enrichment culture assays to detect L. monocytogenes on deli
      meat, and (iii) the fate of L. monocytogenes on sliced deli meats of different
      types during refrigerated storage. Three types of deli meats, uncured oven
      roasted turkey, salami, and bologna containing sodium diacetate and potassium
      lactate, were tested. A five-strain mixture of L. monocytogenes was inoculated at
      ca.10(3) CFU onto the blade of a commercial slicer. Five consecutive meat slices
      were packed per package, then vacuum sealed, stored at 4 degrees C, and sampled
      at 1 and 30 days postslicing. Two sample sizes, 25 g and contents of the entire
      package of meat, were assayed. Total numbers of L. monocytogenes-positive
      samples, including the two sample sizes and two sampling times, were 80, 9, and 3
      for turkey, salami, and bologna, respectively. A higher percentage of turkey meat
      samples were L. monocytogenes positive when contents of the entire package were
      assayed than when the 25-g sample was assayed (12.5 and 7.5%, respectively).
      Lower inoculum populations of ca. 10(1) or 10(2) CFU of L. monocytogenes on the
      slicer blade were used for an additional evaluation of oven-roasted turkey using
      two additional sampling times of 60 and 90 days postslicing. L. monocytogenes
      positive samples were not detected until 60 days postslicing, and more positive
      samples were detected at 90 days than at 60 days postslicing. When BAX-PCR and
      enrichment culture assays were compared, 12, 8, and 2 L. monocytogenes-positive
      samples were detected by both the enrichment culture and BAX-PCR, BAX-PCR only,
      and enrichment culture only assays, respectively. The number of L. monocytogenes
      positive samples and L. monocytogenes counts increased during storage of turkey
      meat but decreased for salami and bologna. Significantly more turkey samples were
      L. monocytogenes positive when the contents of the entire package were sampled
      than when 25 g was sampled. Our results indicate that L. monocytogenes can be
      transferred from a contaminated slicer onto meats and can survive or grow better
      on uncured oven-roasted turkey than on salami or bologna with preservatives.
      Higher L. monocytogenes cell numbers inoculated on the slicer blade resulted in
      more L. monocytogenes-positive sliced meat samples. In addition, the BAX-PCR
      assay was better than the enrichment culture assay at detecting L. monocytogenes
      on turkey meat (P < 0.05).

PMID- 16416904
TI  - Combined effects of antimicrobial coating, modified atmosphere packaging, and
      gamma irradiation on Listeria innocua present in ready-to-use carrots (Daucus
      carota).
AB  - The objective of this study was to evaluate the effect of an edible antimicrobial
      coating combined with modified atmosphere (MA) packaging (60% O2, 30% CO2, and
      10% N2) and gamma irradiation on peeled minicarrots inoculated with Listeria
      innocua. Carrots were inoculated with L. innocua (10(3) CFU/g) and then coated
      with an antimicrobial coating based on calcium caseinate containing trans
      cinnamaldehyde. The same formulation without trans-cinnamaldehyde was used as an
      inactive coating. Coated and uncoated carrots were packed under the MA or under
      air, irradiated at 0.25 or 0.5 kGy, and stored at 4 +/- 1 degrees C for 21 days.
      Samples were evaluated periodically for enumeration of L. innocua. Unirradiated
      carrots stored under air had the highest concentrations of L. innocua after 21
      days of storage: 2.23 CFU/g in the uncoated samples and 2.26 CFU/ g in samples
      coated with the inactive coating. These results suggest that the inactive coating
      did not have any antimicrobial effect against L. innocua. However, the addition
      of the antimicrobial coating resulted in a 1.29-log reduction in the
      concentration of L. innocua in carrots packed under air after 21 days of storage
      and a 1.08-log reduction in carrots packed under MA after 7 days of storage.
      After 7 days of storage, no L. innocua was detected in samples treated at 0.5 kGy
      under air or in samples treated at 0.25 kGy under MA. A complete inhibition of L.
      innocua was also observed during all storage periods in uncoated and coated
      samples treated at 0.5 kGy under MA. These results indicate that the combination
      of irradiation and MA conditions play an important role in the radiosensitization
      of L. innocua.

PMID- 16416905
TI  - Inactivation of Listeria innocua in milk and orange juice by ultrahigh-pressure
      homogenization.
AB  - The aim of this work was to evaluate the bactericidal efficacy of ultrahigh
      pressure homogenization (UHPH) against Listeria innocua ATCC 33090 inoculated
      into milk and orange juice. We also intended to study the effect of inlet
      temperature on the lethality and production of sublethal injuries in this
      microorganism and its ability to survive, repair, and grow in refrigerated
      storage after UHPH treatment. Samples of ultrahigh-temperature whole milk and
      ultrahigh-temperature orange juice inoculated at a concentration of approximately
      7.0 log (CFU per milliliter) were immediately pressurized at 300 MPa on the
      primary homogenizing valve and at 30 MPa on the secondary valve, with inlet
      temperatures of 6.0 +/- 1.0 degrees C and 20 +/- 1.0 degrees C. L. innocua viable
      counts and injured cells were measured 2 h after UHPH treatment and after 3, 6,
      and 9 days of storage at 4 degrees C for milk and after 3, 6, 9, 12, 15, 18, and
      21 days of storage at 4 degrees C for orange juice. Both the inlet temperature
      and the food matrix influenced significantly (P < 0.05) the inactivation of L.
      innocua, which was higher in whole milk at the 20 degrees C inlet temperature.
      The UHPH treatment caused few or no sublethal injuries in L. innocua. During
      storage at 4 degrees C after treatments, counts increased by approximately 2
      logarithmic units from day 0 to 9 in whole milk, whereas in orange juice counts
      diminished by approximately 2.5 logarithmic units from day 0 to 18.

PMID- 16416907
TI  - Real-time quantitative PCR of Staphylococcus aureus and application in restaurant
      meals.
AB  - Staphylococcus aureus is considered the second most common pathogen to cause
      outbreaks of food poisoning, exceeded only by Campylobacter. Consumption of foods
      containing this microorganism is often identified as the cause of illness. In
      this study, a rapid, reliable, and sensitive real-time quantitative PCR was
      developed and compared with conventional culture methods. Real-time quantitative
      PCR was carried out by purifying DNA extracts of S. aureus with a Staphylococcus
      sample preparation kit and quantifying it in the LightCycler system with
      hybridization probes. The assay was linear from a range of 10 to 10(6) S. aureus
      cells (r2 > 0.997). The PCR reaction presented an efficiency of >85%. Accuracy of
      the PCR-based assay, expressed as percent bias, was around 13%, and the
      precision, expressed as a percentage of the coefficient of variation, was 7 to
      10%. Intraday and interday variability were studied at 10(2) CFU/g and was 12 and
      14%, respectively. The proposed method was applied to the analysis of 77 samples
      of restaurant meals in Valencia (Spain). In 11.6% of samples S. aureus was
      detected by real-time quantitative PCR, as well as by the conventional
      microbiological method. An excellent correspondence between real-time
      quantitative PCR and microbiological numbers (CFU/g) was observed with deviations
      of < 28%.

PMID- 16416906
TI  - Molecular characterization of Listeria monocytogenes from natural and urban
      environments.
AB  - Characterization of 80 Listeria monocytogenes isolates from urban and natural
      environments differentiated 7 and 26 EcoRI ribotypes, respectively. Whereas the
      majority of isolates from the natural environment represented L. monocytogenes
      lineage II (12 of 13 isolates), urban isolates grouped evenly into lineages I and
      II (32 and 33 isolates, respectively) and included two lineage III isolates.
      Multilocus sequence typing of all natural isolates and a randomly selected subset
      of 30 urban isolates showed a higher overall diversity (Simpson index of
      discrimination [D] of 0.987 and 0.920, respectively) than did EcoRI ribotyping (D
      = 0.872 and 0.911, respectively). Combined analysis with ribotype and lineage
      data for 414 isolates from farm sources, 165 isolates from foods and food
      processing environments, and 342 human clinical isolates revealed that lineage I
      was significantly more common among human (P < 0.0001) isolates, whereas lineage
      II was more common among isolates from the natural environment, farms, and foods
      (P < or = 0.05). Among a total of 92 ribotypes, 31 showed significant
      associations with specific isolate sources. One ribotype (DUP-1039C) was
      significantly associated with both natural environments and farms. A spatial
      analysis showed a marginal association between locations in the natural
      environment positive for L. monocytogenes and a proximity to farms. Our data
      indicate that (i) L. monocytogenes strains from different sources show a high
      level of diversity; (ii) L. monocytogenes subtypes differ significantly in their
      associations with different environments, even though populations overlap; and
      (iii) a higher proportion of isolates from environmental sources than from human
      clinical cases can be classified into L. monocytogenes lineage II, which supports
      the classification of this lineage as an environmentally adapted subgroup.

PMID- 16416908
TI  - Influence of four retail food service cooling methods on the behavior of
      Clostridium perfringens ATCC 10388 in turkey roasts following heating to an
      internal temperature of 74 degrees C.
AB  - The influence of four food service cooling methods (CM) on growth of Clostridium
      perfringens ATCC 10388 in cooked turkey roasts was evaluated. Raw whole turkey
      roasts were inoculated with C. perfringens spores (approximately 4.23 log CFU per
      roast), vacuum packaged, and heated to an internal temperature of 74 degrees C.
      The cooked roasts were cooled as follows: whole roast cut into four quarters and
      held at 4 degrees C (CM1); whole roast held in a blast chiller (CM2); whole roast
      loosely wrapped and held at 4 degrees C (CM3); and whole roasts (three per bag)
      held at 4 degrees C (CM4). The roasts were analyzed for C. perfringens using
      Shahidi-Ferguson perfringens agar and anaerobic incubation (37 degrees C, 24 h).
      None of the cooling methods met the amended 2001 U.S. Food and Drug
      Administration Food Code guidelines for safe cooling of potentially hazardous
      foods. Times taken for roasts to cool from 57 to 21 degrees C using CM1, CM2,
      CM3, and CM4 were 2.27, 3.11, 6.22, and 8.71 h, respectively. Times taken for
      roasts (21 degrees C) to reach 5 degrees C ranged from 6.33 (CM1) to 19.45 h
      (CM4). Based on initial numbers of C. perfringens, no growth occurred in roasts
      cooled by CM1 or CM2, whereas numbers increased by 1.5 and 4.0 log in whole
      roasts cooled via CM3 and CM4, respectively. These findings indicate that certain
      food service cooling methods for whole cooked turkey roasts may result in
      proliferation of C. perfringens and increase the risk of foodborne illness by
      this pathogen.

PMID- 16416910
TI  - Sensitivities of foodborne pathogens to pressure changes.
AB  - Eight foodborne pathogens were suspended in ultrahigh-temperature whole milk and
      treated at pressure levels of 0.1 to 690 MPa at 21.5 degrees C for 10 min. There
      was no clear trend in pressure resistance between gram-negative and gram-positive
      organisms. The order of the single strains tested, from most to least pressure
      sensitive, was Vibrio parahaemolyticus < Yersinia enterocolitica < Listeria
      monocytogenes < Salmonella enterica serovar Typhimurium < S. enterica serovar
      Enteritidis < Escherichia coli O157:H7 approximately equal to Staphylococcus
      aureus < Shigella flexneri. For each organism there existed a pressure range in
      which log(number of survivors) had a near linear relationship when plotted versus
      treatment pressure level. In this study, a decimal reduction pressure (Dp) value
      was defined and used to measure the sensitivity of these pathogens to pressure
      changes. L. monocytogenes and V. parahaemolyticus were most sensitive to pressure
      changes, and S. flexneri was most resistant. The D(P) values were 16.3 MPa for L.
      monocytogenes, 21.7 MPa for V. parahaemolyticus, and 127.0 MPa for S. flexneri.
      The most pressure-resistant gram-negative bacterium, S. flexneri, and most
      pressure-resistant gram-positive bacterium, S. aureus, were treated at 50 degrees
      C and pressures of 0.1 to 650 MPa for 10 min. High temperature considerably
      enhanced pressure inactivation of these two organisms and affected their
      sensitivities to pressure changes. The effect of treatment time on the D(P)
      values of L. monocytogenes and V. parahaemolyticus was also determined, and it
      was found that it did not significantly affect their D(P) values.

PMID- 16416909
TI  - A probabilistic modeling approach in thermal inactivation: estimation of
      postprocess Bacillus cereus spore prevalence and concentration.
AB  - The survival of spore-forming bacteria is linked to the safety and stability of
      refrigerated processed foods of extended durability (REPFEDs). A probabilistic
      modeling approach was used to assess the prevalence and concentration of Bacillus
      cereus spores surviving heat treatment for a semiliquid chilled food product.
      This product received heat treatment to inactivate nonproteolytic Clostridium
      botulinum during manufacture and was designed to be kept at refrigerator
      temperature postmanufacture. As key inputs for the modeling, the assessment took
      into consideration the following factors: (i) contamination frequency
      (prevalence) and level (concentration) of both psychrotrophic and mesophilic
      strains of B. cereus, (ii) heat resistance of both types (expressed as decimal
      reduction times at 90 degrees C), and (iii) intrapouch variability of thermal
      kinetics during heat processing (expressed as the time spent at 90 degrees C).
      These three inputs were established as statistical distributions using expert
      opinion, literature data, and specific modeling, respectively. They were analyzed
      in a probabilistic model in which the outputs, expressed as distributions as
      well, were the proportion of the contaminated pouches (the likely prevalence) and
      the number of spores in the contaminated pouches (the likely concentration). The
      prevalence after thermal processing was estimated to be 11 and 49% for
      psychrotrophic and mesophilic strains, respectively. In the positive pouches, the
      bacterial concentration (considering psychrotrophic and mesophilic strains
      combined) was estimated to be 30 CFU/g (95th percentile). Such a probabilistic
      approach seems promising to help in (i) optimizing heat processes, (ii)
      identifying which key factor(s) to control, and (iii) providing information for
      subsequent assessment of B. cereus resuscitation and growth.

PMID- 16416911
TI  - Potential sources of microbial contamination in unpasteurized apple cider.
AB  - A study was conducted to identify possible sources of microbial contamination and
      to assess the effect of good cleaning and sanitation practices on the microbial
      quality and safety of unpasteurized apple cider. Raw unwashed apples, washed
      apples, cleaning water, fresh cider, and finished cider samples were collected
      from five Ontario producers over 4 months and microbiologically tested. Total
      coliforms were found in 31, 71 and 38% of the unwashed apple, water, and washed
      apple samples, respectively. Escherichia coli was found in 40% of the water
      samples from one producer alone. The washing step was identified as a potential
      source of contamination, possibly due to water in the dump tanks seldom being
      refreshed, and because scrubbers, spray nozzles, and conveyors were not properly
      cleaned and sanitized. Higher total coliform counts (P < 0.0001) and prevalence
      (P < 0.0001) in fresh cider compared with those in unwashed apples and washed
      apples indicated considerable microbial buildup along the process, possibly
      explained by the lack of appropriate equipment sanitation procedures. Results
      showed that producers who had better sanitary practices in place had lower (P <
      0.001) total coliform prevalence than the rest of the producers. Overall results
      show that good sanitation procedures are associated with improved microbial
      quality of fresh cider in terms of total coliforms and that operators who
      pasteurize and/or UV treat their product should still be required to have a sound
      good manufacturing practices program in place to prevent recontamination.
      Cryptosporidium parvum, an important pathogen for this industry, was found in
      different sample types, including washed apples, water, and fresh and finished
      cider.

PMID- 16416912
TI  - An assessment of sampling methods and microbiological hygiene indicators for
      process verification in poultry slaughterhouses.
AB  - Studies to determine the appropriateness of the use of populations of indicator
      bacteria on poultry carcasses for process verification were undertaken in
      commercial slaughterhouses. Samples were collected from neck skin by excision or
      from whole carcass rinses and were examined for a range of presumptive process
      hygiene indicator bacteria. Coefficients of variation were calculated for each
      bacterial indicator and were significantly lower in excised samples, indicating
      more reproducible bacterial recovery by this sampling method. Total viable counts
      of aerobic bacteria, Enterobacteriaceae, and Pseudomonas in samples collected by
      excision had the lowest coefficients of variation when compared with other
      indicators and were therefore used for further study. The uncertainties
      associated with the quantification of each bacterial indicator were calculated
      and were lowest overall for total viable counts of aerobic bacteria. In general,
      uncertainty was higher for lower bacterial numbers. Results of microbiological
      testing on pooled excised neck skin samples were not significantly different from
      the mean of individually analyzed samples. Bacterial numbers increased by 1 log
      unit when cultures were stored under chilled conditions typical of those used for
      transporting samples to external laboratories, but the increases were not
      significant for Pseudomonas and aerobic bacteria when storage time was less than
      17 h. Weak relationships were identified between bacterial indicator numbers and
      duration of processing, although cleanliness of the processing environment
      diminished visibly during this time. In the plants visited for this study, there
      was a poor relationship between presumptive bacterial indicator numbers and
      process hygiene. Consequently, bacterial analyses for process verification
      purposes may be of limited value.

PMID- 16416913
TI  - Effect of ozonated water treatment on microbial control and on browning of
      iceberg lettuce (Lactuca sativa L.).
AB  - We examined the effect of ozonated water treatment on microbial control and
      quality of cut iceberg lettuce (Lactuca sativa L.). Fresh-cut lettuce was washed
      in ozonated water (3, 5, and 10 ppm) for 5 min at ambient temperature. The native
      bacterial population on the lettuce declined in response to a rise in ozone
      concentration. However, there was no further bacterial reduction (1.4 log CFU/g)
      above 5 ppm ozone. Although ozonated water treatment increased the phenylalanine
      ammonia lyase (PAL) activity of the lettuce stored at 10 degrees C compared with
      the water wash treatment after 1 day of storage, the concentration of ozone did
      not affect PAL activity. The a* value of the residue of the lettuce methanol
      extracts, which reflects the extent of browning, increased dramatically in
      lettuce treated with 10 ppm ozonated water compared with other treatments.
      Treatment with 3 or 5 ppm ozonated water resulted in more rapid changes in the a*
      value than after the water treatment. The combined treatment of hot water (50
      degrees C, 2.5 min) followed by ozonated water (5 ppm, 2.5 min) had the same
      bactericidal effect as treatment with ozonated water (5 ppm, 5 min) or sodium
      hypochlorite (NaOCl, 200 ppm, 5 min), giving a reduction in bacteria numbers of
      1.2 to 1.4 log CFU/g. The ascorbic acid content of the lettuce was not affected
      by these treatments. The combined treatment of hot water followed by ozonated
      water greatly inhibited PAL activity for up to 3 days of storage at 10 degrees C.
      Treatment with this combination greatly suppressed increases in the a* value,
      thus retarding the progress of browning compared with other treatments throughout
      the 6-day storage. NaOCl treatment also inhibited browning for up to 3 days of
      storage. Bacterial populations on the lettuce treated with sanitizers were
      initially reduced but then showed rapid growth compared with that of the water
      wash treatment, which did not reduce bacterial counts initially.

PMID- 16416914
TI  - Pediococcus parvulus gtf gene encoding the GTF glycosyltransferase and its
      application for specific PCR detection of beta-D-glucan-producing bacteria in
      foods and beverages.
AB  - Exopolysaccharide production by lactic acid bacteria is beneficial in the dairy
      and oat-based food industries and is used to improve the texture of the fermented
      products. However, beta-D-glucan-producing bacteria are considered spoilage
      microorganisms in alcoholic beverages because their secreted exopolysaccharides
      alter the viscosity of cider, wine, and beer, rendering them unpalatable. The
      plasmidic glycosyltransferase (gtf) gene of the Pediococcus parvulus 2.6 strain
      isolated from ropy cider has been cloned and sequenced, and its GTF product was
      functionally expressed in Streptococcus pneumoniae. The GTF protein, which has
      glycosyltransferase activity, belongs to the COG1215 membrane-bound
      glycosyltransferase family, and agglutination tests revealed that the enzyme
      enables S. pneumoniae to synthesize beta-D-glucan. PCR amplification and Southern
      blot hybridization showed that the gtf gene is also present at different genomic
      locations in the beta-D-glucan producers Lactobacillus diolivorans G77 and
      Oenococcus oeni I4 strains, also isolated from ropy cider. A PCR assay has been
      developed for the detection of exopolysaccharide-producing bacteria. Forward and
      reverse primers, included respectively in the coding sequences of the putative
      glycosyltransferase domain and the fifth trans-membrane segment of the GTF, were
      designed. Analysis of 76 ropy and nonropy lactic acid bacteria validated the
      method for specific detection of beta-D-glucan homopolysaccharide producer
      Pediococcus, Lactobacillus, and Oenococcus strains. The limit of the assay in
      cider was 3 X 10(2) CFU/ml. This molecular method can be useful for the detection
      of ropy bacteria in cider before spoilage occurs, as well as for isolation of new
      exopolysaccharide-producing strains of industrial interest.

PMID- 16416915
TI  - Rapid separation and counting of viable microbial cells in food by nonculture
      method with bioplorer, a focusing-free microscopic apparatus with a novel cell
      separation unit.
AB  - A nonculture method utilizing a novel apparatus, the bioplorer, was developed.
      The bioplorer is composed of an efficient cell separation unit, a focusing-free
      microscopic device, and an image analysis program. A meat or vegetable suspension
      is poured into the cell separation funnel, and insoluble matter in the sample
      suspension is trapped by prefilters. Microbial cells passing through the two
      prefilters are then trapped by the membrane filter (pore size, 0.4 microm).
      Trapped cells are double-stained with 4',6'-diamidino-2-phenylindole and
      propidium iodide, and the membrane filter is removed and set on the focusing-free
      microscope. A fluorescent image is then recorded. Total numbers of viable and
      dead cells on the membrane filter can thus be determined automatically. One assay
      can be performed within 10 min, which is much faster than the culture method. The
      results obtained with both the nonculture method and the culture method for meat
      and vegetable samples were highly correlated (r = 0.953 to 0.998). This method is
      feasible for the practical purpose of food safety control.

PMID- 16416916
TI  - Efficacy of natural grassland buffers for removal of Cryptosporidium parvum in
      rangeland runoff.
AB  - Our goal for this project was to estimate the retention efficiency of natural
      grassland buffers for Cryptosporidium parvum. Three sets of 16 plots (2.0 by 3.0
      m) were established at 5, 20, and 35% slopes. Within each set of 16 plots,
      residual dry vegetation matter treatments of 225, 560, and 900 kg/ha were
      implemented, along with a noncut control averaging 4,500 kg/ ha. Buffer width
      treatments were implemented by placing cattle fecal material containing known
      loads of C. parvum 0.1, 1.1, or 2.1 m up-slope of the runoff collector. Grassland
      buffers of 1.1 and 2.1 m generated 3.2- to 8.8-log and 3.6- to 8.8-log retention
      of C. parvum, respectively, across the range of residual dry vegetation matter,
      land slope, rainfall, and runoff conditions examined during this project. Buffers
      with an increased percent land slope exhibited improved the retention
      efficiencies, whereas buffers experiencing larger maximum annual runoff events
      exhibited reduced retention efficiencies. Water-quality data from the 0.1-m-wide
      buffer plots (effectively no buffer) demonstrated that the majority of C. parvum
      oocysts (98 to 99.999%) were retained in the fecal matrix for the duration of the
      storm season, irrespective of the presence of a vegetated buffer. In conclusion,
      these results support the assertion that grassland buffers are an effective
      method for reducing animal agricultural inputs of waterborne C. parvum into
      drinking and irrigation water supplies.

PMID- 16416917
TI  - Cryptosporidium contamination in harvesting areas of bivalve molluscs.
AB  - Cryptosporidium contamination was evaluated in areas in Galicia (northwestern
      Spain) where bivalve molluscs are harvested. Galicia is the main mussel-producing
      region in Europe. Data were collected on water contamination of effluents that
      are discharged into these areas. Cryptosporidium spp. were detected by
      immunofluorescence microscopy and molecular methods in 71% of the river water
      samples (n = 7), 64% of raw sewage samples (n = 11), 50% of effluents from
      wastewater treatment plants (n = 16), and 29.3% of the mussel samples (Mytilus
      galloprovincialis, n = 184). Cryptosporidium parvum was identified in all samples
      of contaminated mussels, Cryptosporidium muris was found in three samples of
      effluent from wastewater treatment plants, and Cryptosporidium baileyi was found
      in a sample of raw sewage. Further studies are needed to determine the
      parasitological quality of water in these shellfish harvesting and recreational
      areas. Cryptosporidium could be a public health risk from consumption of raw or
      undercooked contaminated molluscs and use of contaminated waters for recreational
      purposes.

PMID- 16416918
TI  - Evaluation of performance of a commercial monoclonal antibody-based fenitrothion
      immunoassay and application to residual analysis in fruit samples.
AB  - The performance of a commercially available enzyme-linked immunosorbent assay
      (ELISA) kit containing highly sensitive monoclonal antibodies against
      fenitrothion was assessed. The experimentally estimated dynamic range (0.087 to 2
      ng/g) agreed with that established by the kit manufacturer (0.075 to 1 ng/g). The
      linearity of the standard curve produced for the kit-assembled standard solutions
      (slope = -0.3829) agreed with that of the curve produced for the self-made
      standard solutions (slope = -0.3619). The sensitivity (I50 value) and the limit
      of detection for the kit were 0.23 and 0.033 ng/g, respectively. Selectivity of
      the ELISA indicates that the monoclonal antibody can readily distinguish the
      target pesticide from other structurally related analogs and some metabolites
      (oxon forms), with the exception of ethyl O-(p-nitrophenyl) phenyl
      phosphonothionate (EPN), parathion-methyl, and parathion. Methanol was the best
      organic solvent for the kit, with optimal sensitivity observed at a final
      concentration in the well of 10% (vol/vol) or less. Matrix interferences were
      minimized by direct dilution with water (60-fold) of the methanolic extracts
      fromapple and peach samples. To extract fenitrothion from these two agricultural
      products as simply and rapidly as possible, three extraction methods were used.
      The extraction method that involved shaking by hand for 3 min was the best among
      the three methods. High recovery percentages (116.6% for apple and 110.8% for
      peach) were obtained. Validation of the ELISA method was carried out using the
      gas chromatography-mass spectrometry method, resulting in high recovery and close
      correlation of results (r > 0.95). These findings strongly suggest that the ELISA
      kit may be routinely employed for on-site fenitrothion screening of fruit
      samples.

PMID- 16416919
TI  - Polycyclic aromatic hydrocarbons in frying oils and snacks.
AB  - The high incidence of lung cancer observed among Chinese women has been
      associated with exposure to fumes from cooking oil. Polycyclic aromatic
      hydrocarbons (PAHs) are a class of potentially mutagenic substances emitted from
      cooking oils heated at high temperatures. The objective of this study was to
      investigate whether deep frying with different oils under different conditions
      leads to the development of PAHs either in the oil or in the fried product
      (snacks). PAH analysis was carried out with solid-phase extraction followed by
      reverse-phase high-performance liquid chromatography and spectrofluorometric
      detection. Different oils were used to fry chips and extruded snacks in different
      industrial plants (continuous frying) at temperatures between 170 and 205 degrees
      C, and peanut oil was used to fry French fries and fish (discontinuous frying) at
      temperatures between 160 and 185 degrees C. No appreciable differences in PAH
      load was observed in the same oil before and after frying. Both before and after
      frying, the benzo[a]pyrene concentration in oils ranged from trace to 0.7 ppb.
      All the analyzed samples, including oils from fried snacks, had benzo[a]pyrene
      concentrations well below the 2 ppb limit recently proposed by the European
      Community.

PMID- 16416920
TI  - Validation of a PCR-based method for the detection of various rendered materials
      in feedstuffs using a forensic DNA extraction kit.
AB  - A method trial was initiated to validate the use of a commercial DNA forensic kit
      to extract DNA from animal feed as part of a PCR-based method. Four different PCR
      primer pairs (one bovine pair, one porcine pair, one ovine primer pair, and one
      multispecies pair) were also evaluated. Each laboratory was required to analyze a
      total of 120 dairy feed samples either not fortified (control, true negative) or
      fortified with bovine meat and bone meal, porcine meat and bone meal (PMBM), or
      lamb meal. Feeds were fortified with the animal meals at a concentration of 0.1%
      (wt/wt). Ten laboratories participated in this trial, and each laboratory was
      required to evaluate two different primer pairs, i.e., each PCR primer pair was
      evaluated by five different laboratories. The method was considered to be
      validated for a given animal source when three or more laboratories achieved at
      least 97% accuracy (29 correct of 30 samples for 96.7% accuracy, rounded up to
      97%) in detecting the fortified samples for that source. Using this criterion,
      the method was validated for the bovine primer because three laboratories met the
      criterion, with an average accuracy of 98.9%. The average false-positive rate was
      3.0% in these laboratories. A fourth laboratory was 80% accurate in identifying
      the samples fortified with bovine meat and bone meal. A fifth laboratory was not
      able to consistently extract the DNA from the feed samples and did not achieve
      the criterion for accuracy for either the bovine or multispecies PCR primers. For
      the porcine primers, the method was validated, with four laboratories meeting the
      criterion for accuracy with an average accuracy of 99.2%. The fifth laboratory
      had a 93.3% accuracy outcome for the porcine primer. Collectively, these five
      laboratories had a 1.3% false-positive rate for the porcine primer. No laboratory
      was able to meet the criterion for accuracy with the ovine primers, most likely
      because of problems with the synthesis of the primer pair; none of the positive
      control DNA samples could be detected with the ovine primers. The multispecies
      primer pair was validated in three laboratories for use with bovine meat and bone
      meal and lamb meal but not with PMBM. The three laboratories had an average
      accuracy of 98.9% for bovine meat and bone meal, 97.8% for lamb meal, and 63.3%
      for PMBM. When examined on an individual laboratory basis, one of these four
      laboratories could not identify a single feed sample containing PMBM by using the
      multispecies primer, whereas the other laboratory identified only one PMBM
      fortified sample, suggesting that the limit of detection for PMBM with this
      primer pair is around 0.1% (wt/wt). The results of this study demonstrated that
      the DNA forensic kit can be used to extract DNA from animal feed, which can then
      be used for PCR analysis to detect animal-derived protein present in the feed
      sample.

PMID- 16416921
TI  - Comparative analysis of a modified ecolite method, the colicomplete method, and a
      most-probable-number method for detecting Escherichia coli in orange juice.
AB  - The Ecolite High Volume Juice (HVJ) presence-absence method for a 10-ml juice
      sample was compared with the U.S. Food and Drug Administration Bacteriological
      Analytical Manual most-probable-number (MPN) method for analysis of artificially
      contaminated orange juices. Samples were added to Ecolite-HVJ medium and
      incubated at 35 degrees C for 24 to 48 h. Fluorescent blue results were positive
      for glucuronidase- and galactosidase-producing microorganisms, specifically
      indicative of about 94% of Escherichia coli strains. Four strains of E. coli were
      added to juices at concentrations of 0.21 to 6.8 CFU/ ml. Mixtures of enteric
      bacteria (Enterobacter plus Klebsiella, Citrobacter plus Proteus, or Hafnia plus
      Citrobacter plus Enterobacter) were added to simulate background flora. Three
      orange juice types were evaluated (n = 10) with and without the addition of the
      E. coli strains. Ecolite-HVJ produced 90 of 90 (10 of 10 samples of three juice
      types, each inoculated with three different E. coli strains) positive (blue
      fluorescent) results with artificially contaminated E. coli that had MPN
      concentrations of <0.3 to 9.3 CFU/ml. Ten of 30 E. coli ATCC 11229 samples with
      MPN concentrations of <0.3 CFU/ml were identified as positive with Ecolite-HVJ.
      Isolated colonies recovered from positive Ecolite-HVJ samples were confirmed
      biochemically as E. coli. Thirty (10 samples each of three juice types) negative
      (not fluorescent) results were obtained for samples contaminated with only
      enteric bacteria and for uninoculated control samples. A juice manufacturer
      evaluated citrus juice production with both the Ecolite-HVJ and Colicomplete
      methods and recorded identical negative results for 95 20-ml samples and
      identical positive results for 5 20-ml samples artificially contaminated with E.
      coli. The Ecolite-HVJ method requires no preenrichment and subsequent transfer
      steps, which makes it a simple and easy method for use by juice producers.

PMID- 16416922
TI  - Antimicrobial resistance types and genes in Salmonella enterica infantis isolates
      from retail raw chicken meat and broiler chickens on farms.
AB  - Salmonella enterica subsp. enterica serotype Infantis isolates from retail raw
      chicken meat (n = 98) and broiler chickens on farms (n = 70) were examined for
      antimicrobial susceptibility and antimicrobial resistance genes. A total of 15
      antimicrobial resistance types, 14 in meat and 10 in broiler isolates, were
      identified, and 9 of the 15 types were indistinguishable between meat and broiler
      isolates. Resistance to both oxytetracycline and dihydrostreptomycin accounted
      for 94.0% of the resistance types in meat and broiler isolates, and each type
      harbored aadA1 within 1.0 kb of class 1 integron and tetA. Of nalidixic acid
      resistance types, point mutations at 87Asp (GAC) to Tyr (TAC) in the quinolone
      resistance-determining region of gyrA was detected in 10 of 13 meat isolates and
      at 87Asp to Asn (AAC) in four of seven broiler isolates. These findings suggest
      that the antimicrobial resistance of Salmonella Infantis in retail chicken meat
      predominantly originates from broiler chickens.

PMID- 16416923
TI  - Comparison of methods for recovering Vibrio cholerae O1 from ice.
AB  - Alkaline peptone water (1% peptone, 1% NaCl, pH 8.5) and Trypticase soy yeast
      extract broth (TSYB) supplemented with 2.5% NaCl (pH 8.5) or 1% NaCl (pH 7.5)
      were evaluated as enrichment broths for the isolation of Vibrio cholerae O1 from
      ice. Thirty samples of sterile and nonsterile mineral water were inoculated with
      cell suspensions of this bacterium, quickly frozen, and stored for 3 days at--18
      degrees C. After thawing, samples were analyzed by a three-tube most-probable
      number technique. Incubation in TSYB with 2.5% NaCl (pH 8.5) for 18 h at 37
      degrees C yielded the highest recovery of V. cholerae O1 cells (P < 0.05), a
      result that might be attributable to the nutrients and to the NaCl concentration
      of the TSYB, both of which would promote V. cholerae O1 growth and prevent the
      growth of competitive microbiota.

PMID- 16416924
TI  - Influence of antimicrobial compounds and modified atmosphere packaging on
      radiation sensitivity of Listeria monocytogenes present in ready-to-use carrots
      (Daucus carota).
AB  - Radiosensitization of Listeria monocytogenes was determined in the presence of
      trans-cinnamaldehyde, Spanish oregano, winter savory, and Chinese cinnamon on
      peeled minicarrots packed under air or under a modified atmosphere (60% O2, 30%
      CO2, and 10% N2). Samples were inoculated with L. monocytogenes HPB 2812 serovar
      1/2a (106 CFU/g) and were coated separately with each active compound (0.5%,
      wt/wt) before being packaged under air or the modified atmosphere and irradiated
      at doses from 0.07 to 2.4 kGy. Results indicated that the bacterium was more
      resistant to irradiation under air in the absence of active compound. The dose
      required to reduce L. monocytogenes population by 1 log CFU (D10) was 0.36 kGy
      for samples packed under air and 0.17 kGy for those packed under the modified
      atmosphere. The active compounds evaluated in this study had an effect on the
      radiation sensitivity of L. monocytogenes on carrots. The most efficient compound
      was trans-cinnamaldehyde, where a mean 3.8-fold increase in relative radiation
      sensitivity was observed for both atmospheres compared with the control. The
      addition of winter savory and Chinese cinnamon produced a similar increase in
      relative radiation sensitivity but only when samples where packed under modified
      atmosphere conditions.

PMID- 16416925
TI  - Dereplication by automated ribotyping of a competitive exclusion culture
      bacterial isolate library.
AB  - Concerns over the development of antibiotic-resistant bacteria within the food
      animal industry have intensified the search for natural approaches to the
      prevention and treatment of bacterial diseases. Competitive exclusion cultures
      are the foundation of a disease-management strategy based on the use of benign
      bacterial strains to prevent the establishment of pathogenic bacteria within a
      specific host. Differentiation of phenotypically ambiguous isolates is a critical
      step in establishing a manageable library of bacteria for use in the development
      of defined competitive exclusion cultures. We used automated ribotyping
      techniques to dereplicate a large collection of phenotypically ambiguous isolates
      from a continuous-flow competitive exclusion culture. A total of 157 isolates
      were screened following an EcoRI restriction enzyme digestion. The 157 isolates
      were resolved into 23 ribogroups, which represents an 85% reduction in the number
      of isolates in the bacterial isolate library. Seventy-six percent of the isolates
      fit into one of five ribogroups. This work demonstrated that automated ribotyping
      is an effective and efficient tool for dereplication of diverse bacterial isolate
      libraries.

PMID- 16416926
TI  - Recalls of spices due to bacterial contamination monitored by the U.S. Food and
      Drug Administration: the predominance of Salmonellae.
AB  - From 1980 to 2000, the annual per capita consumption of spices in the United
      States increased by 60% (from 1.0 to 1.6 kg per person per year). Although spices
      are known to harbor various molds, fungi, and bacteria, relatively few reports
      have documented this group of foods as the cause of human illness. In recent
      years, however, the U.S. Food and Drug Administration (FDA) has noted an
      increased number of recalls of dried spices due to bacterial contamination.
      Accordingly, we reviewed spice recalls that took place in the United States from
      fiscal years 1970 to 2003. During the study period, the FDA monitored 21 recalls
      involving 12 spice types contaminated with bacterial pathogens; in all but one
      instance, the recalled spices contained Salmonella. Paprika was the spice most
      often involved in the recalls. A wide variety of countries were the source of the
      recalled spices. Using data from the Centers for Disease Control and Prevention
      National Salmonella Surveillance System, we were unable to discern any increases
      in the reported incidence of laboratory-confirmed salmonellosis in states that
      received spices contaminated with selected rare Salmonella serotypes. A variety
      of effective methods exist to disinfect spices, procedures that have attained
      increased importance given the frequent use of spices in ready-to-eat foods and
      the potential for contaminated spices to cause widespread outbreaks.

PMID- 16416927
TI  - [Surgical therapy of colorectal liver metastases].
AB  - The liver is the most common organ of distant colorectal metastases. Liver
      resection currently represents the best and only potentially curative treatment
      for metastatic colorectal cancer isolated to the liver. Five-year survival rates
      of 30 to 40% are reported after curative liver resection. Unfortunately, only 10
      to 20% of patients with liver metastases without extraheaptic disease are
      amenable to surgical resection. Novel therapy strategies to improve
      respectability such as neoadjuvant chemotherapy, portal vein embolisation or
      ligature, resection combined with ablation and two-stage hepatectomy are
      currently evaluated. The overall goal of these treatments is to increase the
      proportion of patients with isolated colorectal liver metastases that can undergo
      curative resection. Despite curative resection, 60 to 70% of patients will
      develop recurrent disease. In case of isolated recurrence to the liver that is
      resectable, repeat liver resection is the treatment of choice. Adjuvant
      chemotherapy is directed to reduce the risk of recurrence after resection.
      Despite few encouraging randomised trials on adjuvant chemotherapy, there are no
      definitive recommendations for adjuvant chemotherapy.

PMID- 16416928
TI  - [Therapy for advanced colorectal carcinoma--new developments and standards].
AB  - Colorectal carcinoma is the second common cause of death from cancer. For a long
      period patients with metastatic disease were considered incurable except for a
      small subgroup with isolated surgically complete removable lesions in the lungs
      and the liver. Chemotherapy was a treatment of unproven value, beneficial in very
      few patients. However, in the last two decades it has become a well-documented
      survival prolonging treatment, postponing tumor symptoms in the majority of
      patients, and potentially curing some patients if combined with aggressive
      surgery.

PMID- 16416929
TI  - [Colorectal carcinoma in elderly patients].
AB  - The median age of patients with newly diagnosed colorectal carcinoma is about 70
      years. Due to a steady rise of the life expectancy in the Western world the group
      of patients being older than 70 to 75 years will grow substantially. This will
      result in increased numbers of colorectal cancers. Patients in this age group are
      underrepresented in controlled clinical trials if not excluded to begin with.
      This is particularly true for trials conducted for adjuvant or palliative
      chemotherapy for colorectal cancer. Partly due to this lack of data leading to
      uncertainty chemotherapy is offered tients. However, the present data for
      patients >70 years show equall effectivity with regard to tumor response. This is
      true for all standard chemotherapy agents, such as 5-FU, folinic acid,
      capecitabine, irinotecan and oxaliplatin. With respect to toxicity some trials
      show an increased risk in toxic side effects for 5-FU-based combination
      therapies. There are no age-specific differences for the other drugs. Therefore,
      patients who are older than 70 years should be offered state-of-the-art
      chemotherapy in the adjuvant as well as palliative setting. For a balanced
      treatment decision one has to take into account the overall performance and
      organfunction alongside the mental and social capacity of the elderly patient.

PMID- 16416930
TI  - [When the tongue impairs breathing].

PMID- 16416931
TI  - [Mountain bike accident].

PMID- 16416932
TI  - ["As soon as you close your eyes, the adventure of sleep begins"].

PMID- 16416933
TI  - [Brazilian Consensus on Chagas disease].

PMID- 16416934
TI  - Evidence-based development of a diagnosis-dependent therapy planning system and
      its implementation in modern diagnostic software.
AB  - The prerequisite for structured individual therapy of craniomandibular
      dysfunctions is differential diagnostics. Suggestions for the structured
      recording of findings and their structured evaluation beyond the global diagnosis
      of "craniomandibular disorders" have been published. Only this structured
      approach enables computerization of the diagnostic process. The respective
      software is available for use in practice (CMDcheck for CMD screening, CMDfact
      for the differential diagnostics). Based on this structured diagnostics,
      knowledge-based therapy planning is also conceivable. The prerequisite for this
      would be a model of achieving consensus on the indicated forms of therapy related
      to the diagnosis. Therefore, a procedure for evidence-based achievement of
      consensus on suitable forms of therapy in CMD was developed first in multicentric
      cooperation, and then implemented in corresponding software. The clinical
      knowledge of experienced specialists was included consciously for the consensus
      achievement process. At the same time, anonymized mathematical statistical
      evaluations were used for control and objectification. Different examiners form
      different departments of several universities working independently of one
      another assigned the theoretically conceiveable therapeutic alternatives to the
      already published diagnostic scheme. After anonymization, the correlation of
      these assignments was then calculated mathematically. For achieving consensus in
      those cases for which no agreement initally existed, agreement was subsequently
      arrived at in the course of a consensus conference on the basis of literature
      evaluations and the discussion of clinical case examples. This consensus in turn
      finally served as the basis of a therapy planner implemented in the above
      mentioned diagnostic software CMDfact. Contributing to quality assurance, the
      principles of programming this assistant as well as the interface for linking
      into the diagnostic software are documented and also published here.

PMID- 16416935
TI  - Designing a framework of intelligent information processing for dentistry
      administration data.
AB  - OBJECTIVES: This study was designed to test a cumulative view of current data in
      the clinical database at the Faculty of Dentistry, Dalhousie University. We
      planned to examine associations among demographic factors and treatments.
      METHODS: Three tables were selected from the database of the faculty: patient,
      treatment and procedures. All fields and record numbers in each table were
      documented. Data was explored using SQL server and Visual Basic and then cleaned
      by removing incongruent fields. After transformation, a data warehouse was
      created. This was imported to SQL analysis services manager to create an OLAP
      (Online Analytic Process) cube. RESULTS: The multidimensional model used for
      access to data was created using a star schema. Treatment count was the
      measurement variable. Five dimensions--date, postal code, gender, age group and
      treatment categories--were used to detect associations. Another data warehouse of
      8 tables (international tooth code # 1-8) was created and imported to SAS
      enterprise miner to complete data mining. Association nodes were used for each
      table to find sequential associations and minimum criteria were set to 2% of
      cases. Findings of this study confirmed most assumptions of treatment planning
      procedures. There were some small unexpected patterns of clinical interest.
      Further developments are recommended to create predictive models. CONCLUSIONS:
      Recent improvements in information technology offer numerous advantages for
      conversion of raw data from faculty databases to information and subsequently to
      knowledge. This knowledge can be used by decision makers, managers, and
      researchers to answer clinical questions, affect policy change and determine
      future research needs.

PMID- 16416936
TI  - Clinical long-term results with 617 Cerec veneers: a nine-year report.
AB  - There are no long-term clinical studies concerning the treatment outcome of
      CAD/CAM generated porcelain laminate veneers. The objective of this study was to
      conduct a longitudinal evaluation of CAD/CAM fabricated porcelain laminate
      veneers. A single practitioner placed 715 CAD/CAM generated porcelain laminate
      veneers produced chairside with the Cerec system on 307 patients between December
      1989 and December 1997. 260 patients with 617 veneers were available for recall
      examination. Forty-seven patients with 98 veneers (13.7%) were unable to be
      located or return for recall examination. Fourteen restorations had been lost.
      The Kaplan-Meier survival rate was 94% after up to 9 years (95% confidence
      interval: 90.7 to 97.8%). Of the surviving restorations, 98% were classified as
      clinically acceptable after 9 years. 97.3% of the teeth examined tested vital,
      96.2% of the veneers were asymptomatic since their production, 98.8% of the
      veneers were considered successful by the patient. CAD/CAM veneers fabricated
      with the Cerec System achieved comparable long-term clinical results to those
      reported for laboratory processed porcelain laminate veneers. The high survival
      rate and favorable clinical results would support the use of CAD/CAM porcelain
      laminate veneers in clinical situations similar to those for laboratory processed
      porcelain veneers. CAD/CAM generated porcelain laminate veneers may provide
      equally good clinical results and longevity as conventional laboratory-processed
      porcelain laminate veneers.

PMID- 16416937
TI  - Is there an ironic tone of voice?
AB  - Research on nonverbal vocal cues and verbal irony has often relied on the concept
      of an ironic tone of voice. Here we provide acoustic analysis and experimental
      evidence that this notion is oversimplified and misguided. Acoustic analyses of
      spontaneous ironic speech extracted from talk radio shows, both ambiguous and
      unambiguous in written form, revealed only a difference in amplitude variability
      compared to matched nonironic speech from the same sources, and that was only
      among the most clear-cut items. In a series of experiments, participants rated
      content-filtered versions of the same ironic and nonironic utterances on a range
      of affective and linguistic dimensions. Listeners did not rely on any set of
      vocal cues to identify verbal irony that was separate from other emotional and
      linguistic judgments. We conclude that there is no particular ironic tone of
      voice and that listeners interpret verbal irony by combining a variety of cues,
      including information outside of the linguistic context.

PMID- 16416938
TI  - English-learning infants' segmentation of verbs from fluent speech.
AB  - Two experiments sought to extend the demonstration of English-learning infants'
      abilities to segment nouns from fluent speech to a new lexical class: verbs.
      Moreover, we explored whether two factors previously shown to influence noun
      segmentation, stress pattern (strong-weak or weak-strong) and type of initial
      phoneme (consonant or vowel), also influence verb segmentation. Our results
      establish the early emergence of verb segmentation in English: by 13.5 months for
      strong-weak consonant- or vowel-initial verbs and for weak-strong consonant
      initial verbs; and by 16.5 months for weak-strong verbs beginning with a vowel.
      This generalizes previous reports of early segmentation to a new lexical class,
      thereby providing additional evidence that segmentation is likely to contribute
      to lexical acquisition. The effects of stress pattern and onset type found are
      similar to those previously obtained for nouns, in that verbs with a weak-strong
      stress pattern and verbs beginning with a vowel appear to be at a disadvantage in
      segmentation. Finally, we present prosodic analyses that suggest a possible
      effect of prosodic boundary and pitch accent distribution on segmentation. These
      prosodic differences potentially explain a developmental lag in verb segmentation
      observed in the present study compared to earlier findings for noun segmentation.

PMID- 16416939
TI  - Judgment of disfluency in people who stutter and people who do not stutter:
      results from magnitude estimation.
AB  - Two experiments used a magnitude estimation paradigm to test whether perception
      of disfluency is a function of whether the speaker and the listener stutter or do
      not stutter. Utterances produced by people who stutter were judged as "less
      fluent," and, critically, this held for apparently fluent utterances as well as
      for utterances identified as containing disfluency. Additionally, people who
      stutter tended to perceive utterances as less fluent, independent of who produced
      these utterances. We argue that these findings are consistent with a view that
      articulatory differences between the speech of people who stutter and people who
      do not stutter lead to perceptually relevant vocal differences. We suggest that
      these differences are detected by the speech self-monitoring system (which uses
      speech perception) resulting in covert repairs. Our account therefore shares
      characteristics with the Covert Repair (Postma & Kolk, 1993) and Vicious Circle
      (Vasic & Wijnen, 2005) hypotheses. It differs from the Covert Repair hypothesis
      in that it no longer assumes an additional deficit at the phonological planning
      level. It differs from the Vicious Circle hypothesis in that it no longer
      attributes hypervigilant monitoring to unknown, external factors. Rather, the
      self-monitor becomes hypervigilant because the speaker is aware that his/her
      speech is habitually deviant, even when it is not, strictly speaking, disfluent.

PMID- 16416940
TI  - The perception of phonological quantity based on durational cues by native
      speakers, second-language users and nonspeakers of Finnish.
AB  - Some languages, such as Finnish, use speech-sound duration as the primary cue for
      a phonological quantity distinction. For second-language (L2) learners, quantity
      is often difficult to master if speech-sound duration plays a less important role
      in the phonology of their native language (L1). By comparing the categorization
      performance of native speakers of Finnish, Russian L2 users of Finnish, and non
      Finnish-speaking Russians, the present study aimed to determine whether the L2
      users, whose native language does not have a quantity distinction, have been able
      to establish categories for Finnish quantity. The results suggest that the native
      speakers and some of the L2 users that have been exposed to Finnish for a longer
      time have access to phonological quantity categories, whereas the L2 users with
      shorter exposure and the non-Finnish-speaking subjects do not. In addition, by
      comparing categorization and discrimination tasks it was found that the native
      speakers show a phoneme-boundary effect for quantity that is cued by duration
      only, whereas the non-Finnish-speaking subjects and the subjects with low
      proficiency in Finnish do not.

PMID- 16416941
TI  - [Refugee politics need to be reformed. Mental health of refugees is promoted by
      prompt access to the same rights as the resident population--also in the long
      run].

PMID- 16416942
TI  - [The apathetic children--a challenge for Swedish child health services].

PMID- 16416943
TI  - [Words can hurt. Well-meaning standardized phrases can increase both pain and
      anxiety].

PMID- 16416944
TI  - [The asylum seeking process a breeding ground for apathy among certain children.
      A negative answer concerning the residence permit is often a triggering factor].
AB  - In this study, 124 of 1,299 children from asylum seeking families living in
      northern Sweden required psychiatric help. Compared to Swedish children a larger
      proportion seeks psychiatric help. In the last few years more children seeking
      asylum have had severe generalised losses of functions and need help with
      activity of daily life. Almost every child's health condition improves when they
      get permission to stay in Sweden. Children from the former Soviet Union seek help
      more frequently than children from other countries do.

PMID- 16416945
TI  - [Quinolones--a cure which became a threat. Accelerating resistance development
      demands stricter indications].
AB  - Fluoroquinolones are important antibiotics for treatment of serious infections.
      Increased usage has, in many countries, resulted in rapid development of
      resistance towards this class of antibiotics. Moreover, it has been shown that
      use of fluoroquinolones is associated with selection of multi-resistant bacteria,
      such as methicillin-resistant S. aureus and vancomycin-resistant enterococci. The
      risks related to overuse of fluoroquinolones among both humans and animals are
      reviewed and strict indications for use are suggested.

PMID- 16416946
TI  - [Rare bacteria species found in wounds of tsunami patients. Predominance of gram
      negative rods, increased antibiotic resistance].
AB  - Microbiological cultures from 229 patients seeking medical advise in Stockholm
      after the tsunami catastrophe December 2004 were analysed at the Clinical
      microbiology laboratory, Karolinska University Hospital, Stockholm, Sweden. Gram
      negative rods were the most common findings from wound cultures. Common human
      pathogens as Escherichia coli, Proteus species, Klebsiella spp, and Pseudomonas
      aeruginosa were isolated. However, more rare species of gram-negative rods were
      also isolated, e.g. Myroides odoratus, Sphingomonas paucimobilis and Bergeyella
      zoohelcum. Resistance towards ordinary antibiotics was higher compared to our
      Swedish reference material for Escherichia coli, Klebsiella pneumoniae, Proteus
      mirabilis and Acinetobacter spp, but not for Pseudomonas aeruginosa. Possibly,
      this reflects that the resistant isolates were nosocomially acquired in Asia.

PMID- 16416947
TI  - ["Not the doctor's pigeon"--a common dilemma in sick-listing consultations].
AB  - The role played by doctors in the high sick-listing figures is a subject of
      vigorous discussion. The point of departure for the course "The
      generalpractitioner and the medical certificate" is that the doctor can combine
      concern for the patient with objective assessment. With the course participants'
      own sick-listing cases as material, it has been possible to categorize the
      difficulties. One such category is "Not the doctor's pigeon", when the doctor
      sees that the patients' problems concerning sick-listing would be better handled
      by, for example, the employer, the employment office, the social insurance
      office, or the patient himself. The categories found can be regarded as a
      practical support for the doctor in considering and discovering alternative
      actions.

PMID- 16416948
TI  - [Abortion--a taboo right. Women's complex experiences include both relief and
      pain].
AB  - Women resort to abortion in all possible contexts and the motives for abortion
      reflect the need of women for planned parenthood. Women's experiences of abortion
      are complex; the abortion is experienced as a relief and regarded as a form of
      exercising responsibility. This does not exclude ethical reasoning or
      simultaneous painful feelings. As long as abortion is understood primarily as a
      last resort among special risk groups and not as a phenomenon which reflect
      reproductive expectations among all groups in society, abortion will retain its
      image as something taboo. In addition, as long as women's complex considerations
      and experiences in relation to abortion remain hidden the myths about abortion
      will live on.

PMID- 16416949
TI  - [A denial with catastrophic consequences].

PMID- 16416950
TI  - [The Annual Meeting of the Medical Society: psychiatry of tomorrow in focus].

PMID- 16416951
TI  - [Time for Sweden to recognize the right to health care in other European Union
      countries].

PMID- 16416952
TI  - [The "Refugee children with apathetic symptoms" by the National Board of Health
      and Welfare: An inadequate official document--where is the child, the care?].

PMID- 16416954
TI  - [The JO company's reply on juice and sugar: the label symbol is for misinformed
      consumer].

PMID- 16416953
TI  - [If good hand hygiene routines are not followed no private rooms in the world
      will help].

PMID- 16416955
TI  - Position of SARB in regard to premedication.

PMID- 16416956
TI  - Basic principles of disaster medical management.

PMID- 16416957
TI  - ATLS approach to trauma management.

PMID- 16416958
TI  - The cervical spine in trauma: implications for the anaesthesiologist.
AB  - In this paper, the authors review the most recent literature concerning the
      management of the cervical spine in trauma patients. They address the main topics
      of concern for the anaesthesiologist including pre-hospital care, clearance of
      the cervical spine, neuroprotective therapies, difficult tracheal intubation, and
      management during general anaesthesia, in the intensive care unit and in
      paediatric patients. The most widely accepted strategies are provided as well as
      alternative options.

PMID- 16416959
TI  - Pediatric trauma.

PMID- 16416960
TI  - Mechanisms of injury in vehicular trauma.

PMID- 16416961
TI  - [Mass casualty management: lessons for the future].

PMID- 16416962
TI  - [sdt1, a novel Arabidopsis mutant tolerant to drought and high-salinity
      stresses].
AB  - Among the 20000 independent Arabidopsis activation tagging lines, we screened a
      novel mutant with high-salinity and drought tolerance, namely sdt1 (high-salinity
      and drought tolerant 1). sdt1 kept normal growth under drought stress by
      consecutively withholding water for 26d, while all the wild type wilted to death.
      Furthermore, the same result was repeated under high-salinity stress when sdtl
      and wild type were treated with 150 mmol/L NaCl. Seeds germination test on the
      medium indicated that the response of sdt1 to endogenous or exogenous ABA was
      reduced as compared with wild type. Under drought stress conditions the rates of
      water loss of sdt1 rosette leaves were significantly lower than that of wild
      type. Southern hybridization of sdt1 and the result of high-salinity tolerance
      genetic analysis showed that two copies of T-DNA were inserted into the two
      linking sites by shoulder to shoulder.

PMID- 16416963
TI  - [Study on identification, colonization and reorganization of rice endophytic
      bacteria].
AB  - Endophytic SR-15, SR-25 and SL-37 strains screened from rice hybrid D you 527 in
      Sichuan were analyzed. Through penetration and microscopic test, the strains were
      found be mainly located in the cell gap, vacuole and cytoplasm. PUC18
      transferring and ERIC-PCR showed that the recombination strain SR-15 could grow
      in the plant stably. The strain was identified as Bacillus halmapalus based on
      its chemical components of cell wall, physiological and biochemical characters.
      It was also shown that the strain was not injurious to rice plant, instead, it
      promoted rice plant growth by penetration. The Cry1Ac gene was transferred into
      the stain and verified by Southern analysis. Cry1Ac-transferred SR-15 was toxic
      to the Chilo suppressalis, brought about death ratio as high as 84.2%.

PMID- 16416964
TI  - [A new culture method for primordial germ cell].
AB  - To investigate the new method that the primordial germ cells (PGCs) can long time
      propagate, grow and keep potency of differentiation in vitro. PGCs were co
      cultured with Sertoli cells (SCs) or with homologue fibroblasts from genital
      ridge. When co-cultured with SCs, PGCs colonies and times of transfer of culture
      were greater than those co-cultured with homologue fibroblasts. At present PGCs
      of co-cultured with SCs have succeeded in subculturing to the 51 generation. SCs
      can availably enhance propagating ability as well as a long period of time
      maintain the characteristic of PGCs.

PMID- 16416965
TI  - [An anti-tumor research of recombinant phage vaccine expressed xenogenic EGFR].
AB  - A recombinant phage vaccine expressing EGFR on it's capsid was constructed and
      used to study the anti-tumor effect. The T7 phage display system was applied to
      display seven xenogenic (human, chicken) epidermal growth factor receptor
      extracellular domain fragments. The EGFR fragment was expressed as fused protein
      with 10B capsid on the surface of T7 phage. The T7-EGFR phage vaccines were
      injected into C57BL/6J mice, and then Lewis lung cancer cells were inoculated
      after 4 weeks immunization. The tumor tissue was excised and weighed after 10
      days to evaluate the anti-tumor effect of each experimental group. The EGFR
      expression of the phage vaccine was verified by western-blot analysis. The A431
      cells with high expressed EGFR was used to detect the anti-EGFR antibody by flow
      cytometry analysis. The results showed that the A431 cell can react with the
      serum obtained from the mice after three-week immunization. The experimental
      results confirmed that special EGFR antibody could be induced by the T7-EGFR
      phage vaccine. The T7-EGFR phage vaccine can elicit endogenous special EGFR
      antibody in mice and is capable of suppressing the tumor proliferation and
      retarding the growth of Lewis lung cancer. This research can be used to develop
      an anti-tumor vaccine for the target-therapy of EGFR(+) tumor.

PMID- 16416966
TI  - [Studies on the megasporogenesis and microsporogenesis and the development of
      their female and male gametophyte in Magnolia biloba].
AB  - The anther of Magnolia biloba is tetrasporangiate with glandular tapetum, which
      consists of one or two layers of cells. Cytokinesis during meiosis of its
      microspore mother cell is modified simultaneous type, and the microspore tetrads
      are isobilateral. Mature pollen grains are two-celled. Tetrad cells and
      microspores are irregularly shaped during the microsporogenesis. There were two
      ovules on the ventral surface of unicarpellate ovary wall. Ovules were
      anatropous, bitegmnous and crassinucellar. Archesporial cell was one cell and
      differentiated from cell in the second layer beneath epidermis. The development
      of the embryo sac conformed to the polygonum type. The embryological
      characteristics of Magnolia biloba are very similar to those of other species in
      Magnoliaceae. The megasporogenesis and microsporogenesis and the development of
      their female and male gametophyte are partially abnormal. Abnormal phenomena in
      the process of reproduction of Magnolia biloba causing this species to be
      endangered was discussed.

PMID- 16416967
TI  - [The ultrastructural observation of anthers of Chinese cabbage's mail-sterility].
AB  - The fertile and sterile anthers of a Chinese cabbage (Brassica campestris L. ssp.
      chinensis Makino) were observed using electron microscope to find the
      ultrastructural feature of sterile anthers. The earliest abnormal phenomenon in
      sterile anther was nucleolus of sporogenous cells locating in the edge of
      nucleus. During microspore mother cell development, callus wall surrounding the
      cell displayed uneven in the thick ness and was discontinuous,and the some
      cytoplasm leaked out of the cell from some rifts in the wall. After meiosis of
      microspore mother cells, the cells of tetrad were irregular and some of them
      contained several nuclei. The exine of pollen began to be formed in tetrad in
      this cabbage. The evident disorder during exine formation in the sterile pollen
      occurred during its primexine formation and then the sporopollenin was
      irregularly deposited to form a layer of uneven and discontinuous pollen exine.
      Cytoplasm of aborting microspores contracted and finally degenerated after them
      released from tetrad. The tapetal cells of fertile anther began to synthesis
      abundant lipid material during microspore development. However, the tapetal cells
      of sterile anther did not synthesis lipid material during microspore aborting.
      The microspore abortion was first and tapetal degeneration second. Therefore,
      aborting microspore induced the functional default of tapetal cells synthesizing
      lipid material. The ultrastructural results on this study further complete and
      correct our previous results obtained by light microscope.

PMID- 16416968
TI  - [Expression patterns of GCN5 and HDAC1 in preimplantational mouse embryos and
      effects of in-vitro cultures on their expressions].
AB  - To investigate the expression patterns of histone acetyltransferase (GCN5) and
      histone deacetylase 1 (HDAC1) in preimplantation mouse embryos and the effects of
      in-vitro cultures on their expressions, immunocytochemistry was used to detect
      the expressions of GCN5 and HDAC1 in mouse embryos at the stages of two-cell,
      four-cell, eight-cell, morula and blastocyst in both in-vivo and invitro groups.
      In in-vivo group, the obvious expressions of GCN5 were observed in the cytoplasm
      of all kinds of mouse embryos but blastocysts. Meanwhile, HDAC1 was highly
      expressed in the nuclei of four and eight-cell embryos and morula but mainly seen
      in the cytoplasm of two-cell embryos. In blastocysts, the HDAC1 fluorescence was
      limited to the nuclei of trophoblast cells. In in-vitro group, there were no
      obvious GCN5 expressions in all kinds of embryos and the expression of HDAC1 was
      significantly reduced although its expression pattern was similar to that of in
      vivo group. Those results showed that in -vitro culture environments could
      inhibit GCN5 expression and decrease the expression of HDAC1 in mouse
      preimplantation embryos, which might affect the correct embryonic gene
      expression.

PMID- 16416969
TI  - [Cytokinin changes of root exudates, leaves and grains in inter-subspecific
      hybrid rice].
AB  - Using inter-subspecific hybrid rice of IIyou 2070 and IIyou 419 , their restorer
      lines 2070 and Zhong419, the various forms and levels of root-derived
      cytokinins(CTKs) in root exudates, and changes of various forms of cytokinins in
      rice flag leaves and grains were analyzed by HPLC and ELISA after initial heading
      stage. The results indicated that zeatin had 62.8% to 89.1% of total cytokinins
      and was the dominant form of cytokinins in root exudates during early grain
      filling, whereas, the contents of diHZ and diHZR greatly increased during milk
      ripening. This change was consistent with the dynamic changes of ZRs (Z+ZR)and
      diHZRs (diHZ+diHZR)in flag leaves of IIyou 2070 and 2070. Different from main
      cytokinin composition in root exudates, IPAs took high proportion of total CTKs
      in leaf and grain. We suggested that there were changes of various forms and
      activities of root-derived cytokinins in root exudates, and this change was
      related to catabolic enzymes of cytokinins and the different expression of enzyme
      genes. Meanwhile, the relationship between cytokinin changes of vigorous and weak
      spikelets and grain filling was disscused.

PMID- 16416970
TI  - [Hyperplasia and aggregation of mitochondrion in Pisum sativum leaf cells
      infected with BBWV 2].
AB  - The alteration of mitochondrion in Pisum sativum leaf cells infected with
      B935,isolates of BBWV 2, were investigated by electron microscopy, immunogold
      labeling technique and stereologic quantity. The results showed that mitochondria
      were hyperplastic and aggregated nearby the membranous proliferation in
      cytoplasm. Many mitochondria were enlarged and distorted. There are some square
      paracrystalline inclusions within abnormal mitochondria. The difference between
      infected and healthy leaf cells at mitochondrion was observed to reveal
      significances in volume density (V(V)), surface density (S(V)), numerical density
      (Nv)(P < 0.01), but it was varied in form factor (PE), circumference index (CI),
      ratio of surface to volume (R(SV)). Some immunogold particles were localized to
      the crystal substance between the mitochondria. A high density of immunogold
      particles were localized to the crystalline aggregates and tubules composed of
      virus particles. This indicated that hyperplasia and aggregation of mitochondrion
      related to the assembly of virion in infection cells. BBWV 2 particles were
      assembled at the position of adherent mitochondria. The paracrystalline
      inclusions within mitochondria could represent the accumulation of a certain
      protein.

PMID- 16416971
TI  - [Cloning and expression of murine alpha1,2-fucosyltransferase gene].
AB  - MFUT-II, a DNA fragment encoding murine alpha1,2-fucosyltransferase,was cloned by
      RT-PCR. The open-reading frame was ligated into mammalian expression vector pcDNA
      3.1 (pcDNA3.1-MFUT-II) and was transiently transfected into COS-7 cells using a
      Cellphect Transfection kit. Moreover, the expression of the gene in murine
      tissues was analyzed with Northern hybridization showing a 3.5-Kb mRNA transcript
      product in several tissues. The existence of MFUT-II was detected by Southern
      blot. MFUT-II was found to be a new member of the murine alpha1,2-FT gene family.
      Its open reading frame encoded 347 amino acids with a predicted molecular mass of
      39.21 kDa and exhibited sequence homology with murine H & Sec1 gene. MFUT-II also
      exhibited sequence homology with Human Se gene (79.0%), Rat FTB gene (89.0%) and
      Rabbit FT-III gene (77.0%), respectively. COS-7 cells transfected with pcDNA3.1
      MFUT- II showed alpha 1,2-fucosyltransferase activity. Southern analysis revealed
      that MFUT-II was present in the mouse genome as a single-copy gene. In
      conclusion, MFUT-II was a murine Se gene.

PMID- 16416972
TI  - [Immunocytochemical localization of estrogen receptor in the oogenesis of
      termites].
AB  - The expression of estrogen receptor(ER) was examined in the oogenesis of termites
      (Reticulitermes aculabialis) with immunocytochemical localization method. The
      results showed ER existed in oocytes at the process of differentiation and the
      process of growth. ER immunopositive substance was localized in the nucleus of
      oocytes at the differentiation stage and (the cytoplasm of oocytes at the growth
      stage. On the other hand,previous studies have demonstrated the procerebrum of
      termites could secrete FSH (Follicle Stimulating Hormone)and LH (Luteinizing
      Hormone) which stimulated estrogen secreting. These results provide a new
      morphological proof that "brain-gonad" participates in the regulation of the
      oogenesis of termites, as have been shown in mammal.

PMID- 16416973
TI  - [Prokaryotic expression, antiserum preparation and cytochemical analysis of
      TaMlo3 in wheat].
AB  - Mlo gene in wheat is critical to determine wheat broad spectrum disease
      resistance against the pathogenic powdery mildew fungus. According to wheat
      TaMlo3 cDNA sequence, the two DNA fragments encoding the intracellular loop 2 and
      C-terminus of wheat Mlo protein were cloned respectively into the vector pET-30a,
      and then the fusion polypeptides were expressed in E. coli BL21. The recombinant
      proteins were purified by Ni2+ -NTA agarose column, and then were used to
      immunize the rabbits respectively. Two polyclonal antisera were obtained and they
      could be specifically bound on the extrahaustorial membrane and extrahaustorial
      matrix of the powdery mildew fungus by immuno-gold labeling.

PMID- 16416974
TI  - Study on total cell antioxidant capacity in Leber's hereditary optic neuropathy.

PMID- 16416975
TI  - Ethical footprints: finding a way through the research process.

PMID- 16416976
TI  - A critical account of obtaining research governance approval.
AB  - Research governance strategies, as currently operated are potentially limiting
      the conduct of research, especially multi-centre studies. The authors provide an
      overview of the current research governance framework in the UK and, using the
      example of one study as an illustrative case, describe and discuss a research
      team's experience of gaining research governance approval for a multi-centre
      study.

PMID- 16416977
TI  - Patient confidentiality, clinical data and NHS research--a researcher's guide.
AB  - More stringent research governance in the NHS has led to an increased focus on
      the importance of patient confidentiality. But relatively low levels of knowledge
      of the Data Protection Act and common law duty of confidentiality among some
      researchers and research managers cause difficulties in getting research projects
      off the ground. The authors outline the main issues surrounding research, data
      protection and patient confidentiality, and provide guidance for researchers,
      clinicians and managers on how to conduct research appropriately.

PMID- 16416978
TI  - Reflections on how to write and organise a research thesis.
AB  - Writing up research projects and presenting a thesis are among the most
      challenging and time-consuming elements of the research process. The authors
      provide a structured guideline to help students, particularly those undertaking
      Master's degrees while still practising in clinical areas, to overcome the
      challenges of writing their thesis and produce a cogent, logical and reflective
      piece of work.

PMID- 16416979
TI  - Non-participant observation: using video tapes to collect data in nursing
      research.
AB  - Observation is a highly valued and effective research method, as well as being an
      essential part of nursing practice. The authors explore the way in which non
      participant observation as a research method might be enhanced by the use of
      video recording. The utility, ethical considerations and constraints of video
      recording as a data collection tool are discussed, with examples from a research
      study. The authors argue that the use of videos can enhance the credibility of
      non-participant observation studies through the minimisation of selectivity and
      bias and the opportunity to employ more rigorous strategies for ensuring
      reliability.

PMID- 16416980
TI  - Using the Internet to conduct research.
AB  - The internet has become an everyday communication tool for countless people
      throughout the world. It has a variety of potential uses in education, practice
      and research, but only in the last decade have nurse researchers begun to take
      advantage of the multiple uses the internet has to offer. The author reviews the
      uses of the internet to conduct research and addresses challenges and issues that
      currently influence web-based research.

PMID- 16416981
TI  - Triangulation as a method for contemporary nursing research.
AB  - The complex nature of phenomena investigated by nurses demands the use of a
      multifaceted approach to develop nursing knowledge. Triangulation offers a
      rigorous methodological framework by which to achieve this aim. The authors
      describe the historical and philosophical underpinnings of triangulation and
      outline considerations in relation to applying it in contemporary nursing
      research.

PMID- 16416982
TI  - Making the most of opportunities...

PMID- 16416983
TI  - [The influence of the estrogens on a retinal blood vessels].
AB  - PURPOSE: To define the influence of the estrogens on a retinal blood vessels.
      MATERIAL AND METHODS: 20 healthy women, mean age 23.5 +/- 1.55 with normal
      laboratory investigations and with regular fundus and blood vessels appearance,
      participated in our study. Fundus examination was performed with fundus camera
      Canon NF 505 and with HRT II. The measurements were made before estrogens
      application (300 microg dermal plasters) and 36 hours after the application in
      4th and 6th day of a period. RESULTS: The difference between the size of the
      retinal vessels before and after estrogens application was significant in all
      cases. In the main branches the increase of a vessel's diameter was 4.4% to
      11.22% (mean 7.61% +/- 3.210%), p<0.05. The increase in a smaller branches of
      central retinal artery balanced from 1.2% to 9.2% (mean 5.47 +/- 4.11%), p<0.05.
      CONCLUSIONS: Estrogens have a great vasodilatation effect on a retinal blood
      vessels. The level of the dilatation after the estrogens' application is about 8%
      in main branches and about 5% in a smaller vessels.

PMID- 16416984
TI  - [Influence of prenatal exposition for selenium on visual evoked potentials (FVEP)
      in rats].
AB  - Selenium is an essential trace element in lower concentration and toxic in higher
      one. The aim of the study was to find out if the small doses of selenium taken by
      pregnant rats change the visual evoked potential (FVEP) curve in newborns. The
      FVEP was done in 4-6 month old white, Wistar, offsprings rats. 8 rats were from
      the mothers which drank water solution of natrium selenosum in dose 1.5 ppm
      through the whole pregnant time ( selen group) and 8 rats were from the pure farm
      (control group). The shortened of the latencies and increased of the amplitudes
      of N1 and P1 waves were observed in the selenium exposed group in comparison to
      the control, but only the changes between amplitudes of N1 and P1 were
      statistically significant. The small doses of selenium by improving the VEP may
      probably change for the better vision too.

PMID- 16416985
TI  - [Bacterial flora of conjunctival sac in patients with cataract. Methods of
      disinfection and evaluation of their efficiency].
AB  - PURPOSE: 1) To evaluate the microbacterial flora of the conjunctival sac and the
      sensitivity of the isolated microorganisms to 0.3% gentamicin solution and 5.0%
      PVP-Jodi solution, which is used to disinfect conjunctival sac. 2) To evaluate
      the role of the adhesive foil in prevention of the infection of the operative
      field. MATERIAL AND METHODS: 170 patients with senile cataract were examined.
      Before admission to Ophthalmology Department each patient received 0.3%
      gentamicin solution three times a day. All patients had their conjunctival sac
      disinfected with the use of 5% PVP-Jodi before surgery. Patients were divided
      into two groups. In the first group (120 patients), first samples were taken on
      admission to the Ophthalmology Department. Next in the day of the procedure, in
      the operation room--first before and second after disinfection of conjunctival
      sac. Adhesive foil was not used in this group. In the second group (50 patients),
      we used adhesive foil before surgery and samples were taken before and after
      disinfection of conjunctival sac. RESULTS: On admission, positive cultures were
      obtained in 40.0% cases. Most of the bacterial flora were Gram-positive bacteria.
      The number of the positive cultures before disinfection with 5.0% PVP-Jodi
      solution diminished to 5.8%, compared with positive results obtained on admission
      to the Ophthalmology Department. Secondary infection of the conjunctival sac has
      been revealed in 10% after disinfection with the use of the 5.0% PVP Jodi. It was
      due to bacterial flora coming from the skin and limbs of the lids (in the group
      without adhesive foil), whereas positive samples were obtained in 2.0% in the
      group where adhesive foil was used. CONCLUSIONS: 1) Gentamicin significantly
      reduces the amount of bacterial flora in conjunctival sac in patients before
      cataract surgery. 2) Adhesive foil is efficient to protect operative field from
      infection.

PMID- 16416986
TI  - [Bacteriological contents of conjunctival sac in patients with cataract in the
      early post-operative period].
AB  - PURPOSE: Evaluation of conjunctival microflora in patients with cataract, during
      the early post-operative period. MATERIAL AND METHODS: One hundred twenty
      patients scheduled for cataract extraction were evaluated. In each patient,
      conjunctival swab was taken directly after cataract surgery and two to three days
      postoperatively. Following surgical procedure all patients received topical
      antibiotics alone or along with steroids. The agents were placed into
      conjunctival sac of the operated eye. Ophthalmic ointments were administered HS
      and eye drops QID. RESULTS: 9.2% (11 patients) of the cultures of conjunctival
      swabs collected right after surgical procedure were positive for growth with
      predominantly Gram-positive organisms, mainly Staphyloccocus spp. These, were
      compared with 24.2% (29 patients) of positive cultures from conjunctival swabs
      collected two to three days later. 4.2% of the latter were also positive when
      taken in the operating room, immediately after a surgical procedure. The
      remaining 20.0% of positive cultures swabbed two to three days after surgery were
      resulted from the contamination of conjunctival sac with germs during the
      postoperative hospitalisation. CONCLUSIONS: There is a risk of early post
      operative infection in patients undergoing cataract surgery. It is caused by the
      appearance of microflora in the conjunctival sac.

PMID- 16416987
TI  - [Antibiotic resistance of conjunctival bacterial flora in children].
AB  - PURPOSE: To evaluate conjunctival bacterial flora in children and its resistance
      to the most frequently antibiotics used by the ophthalmologists in Poland.
      MATERIAL AND METHODS: Bacterial conjuntival cultures obtained in 593 children
      without ocular infections. RESULTS AND CONCLUSIONS: Pathogenic bacterial isolates
      were identified in 26.3% children. Most frequently isolated were Gram-positive
      cocci (70.5%). Significant resistance of Gram-positive cocci to aminoglicosides
      (5% to 65%) was observed. Emerging resistance to fluoroquinolones, especially of
      coagulase-negative staphylococci (in 21%), was also observed.

PMID- 16416988
TI  - Comparative analysis of the eye function and complications after removal of
      complicated cataract due to uveitis and senile cataract.
AB  - PURPOSE: retrospective, comparative analysis of the effectiveness of the results
      among patients who underwent removal of complicated cataract due to uveitis and
      senile cataract. MATERIAL AND METHODS: Patients with cataract enrolled in this
      study were divided into two groups. Group 1 comprised 30 eyes with complicated
      cataract due to uveitis. The main causes of uveitis were: rheumatoid arthritis in
      8 eyes, ankylosing spondylitis in 7, Reiter syndrome in 3, psoriatic arthritis in
      3, systemic sarcoidosis in 2, post-traumatic uveitis in 1. In 6 patients (6 eyes)
      the etiology of uveitis was unknown. Group 2 comprised 30 eyes with senile
      cataract. In 5 patients in each group there were coexisting glaucoma. In both
      groups phacoemulsification or phacoaspiration and foldable three piece IOL
      implantation were performed. The follow-up period was 12 months. Best corrected
      visual acuity and intra and postoperative complications were taken into
      consideration. RESULTS: There were no differences in gender and cataract hardness
      between the two groups. Significantly younger patients were in group 1 p< 0.01.
      Mean preop./ postop. visual acuity was better in group 2 as compared with group
      1: 0.4/ 0.8 and 0.2/ 0.5, respectively, p < 0.01. In both groups however, the
      preoperative visual acuity was significantly lowest in patients with coexisting
      glaucoma: group 1, 0.1 p < 0.01 and in group 2: 0.25 p < 0.001. Significantly
      more frequent intraoperative complications were observed in group 1 as compared
      with group 2 e.g., corneal burn 10% and 6.6%, local sphincter damage 10% and 0%,
      zonular rupture 10% and 3.3% respectively. Similarly, in the late postoperative
      period more frequent complications were observed in group 1 than in group 2 e.g.:
      secondary cataract 50% and 13.3%, IOL decentration 40% and 6.6%, capsule
      contraction 80% and 10%, glaucoma 10% and 3.3% respectively. Recurrence of
      uveitis was observed in 30% of eyes in group 1. CONCLUSIONS: Although the modern
      microsurgical technology and IOL implantation have led to more effective
      treatment of senile cataract, the surgery of complicated cataract due to uveitis
      is still not free from complications. Future surgical strategy of complicated
      cataract owing to uveitis has to comprise the most adequate qualification
      criteria e.g. choice of the optimal period for surgery and the most convenient
      surgical technique as well as the most effective perioperative anti-inflammatory
      treatment.

PMID- 16416989
TI  - [Microincision cataract surgery].
AB  - PURPOSE: To describe the technique of microincision cataract surgery and to
      present own initial results of this procedure. MATEDAL AND METHODS: 73 eyes with
      senile uncomplicated cataract were operated. In 35 eyes traditional
      phacoemulsification was performed, in another 35 eyes phacoemulsification through
      microincision was done with implantation of Acri. Smart 46S and in 3 eyes with
      implantation of AcrySof SA30AL. RESULTS: In first part the differences between
      traditional phacoemulsification and through microincision, were described in
      detail. In our material we noted that microincision cataract surgery gives better
      visual acuity and less astigmatism in early postoperative period. CONCLUSIONS:
      Phacoemulsification of cataract through microincision seems to be a promising
      technique, with some advantages over traditional phacoemulsification.

PMID- 16416990
TI  - [Ophthalmological tests value in detection of the optic neuropathy associated
      with pituitary tumours].
AB  - PURPOSE: To evaluate the value of ophthalmological tests in detection of the
      optic neuropathy associated with pituitary tumours. MATERIAL AND METHODS: 38
      patients with pituitary tumours in 21-73 years old, were examined. Routine
      ophthalmological examination, kinetic and static perimetry (screening test,
      "white-on-white" and "blue-on-yellow") and PVEP were performed. RESULTS: In
      patients with recurrent tumours (group II) more changes was observed in routine
      ophthalmological examination, perimetry and PVEP compared to patients with early
      detected pituitary tumours (group I). No patient of group I present changes in
      routine ophthalmological examination, but they had visual field defects and/or
      abnormal PVEP. In group I in Ps B-Y more visual field defects was detected than
      in kinetic perimetry (p<0.025). In the same group hemifield PVEP was more often
      abnormal than full-field PVEP (p<0.01). In group II similar differences were not
      observed. CONCLUSIONS: In patients with pituitary tumours the most useful test in
      the optic neuropathy diagnosis are "blue-on-yellow" static perimetry and
      hemifield PVEP.

PMID- 16416991
TI  - Applicability of ultrasound in ocular tumors in children and adolescents.
AB  - PURPOSE: Evaluation of the applicability of ultrasound in children diagnosed for
      neoplasm of the eye. Evaluation of Doppler ultrasound in visualizing blood
      vessels within the lesion in eye ball, eye socket and eye lids. Establishing the
      value of the obtained data concerning the image of vessels and blood flow for the
      diagnosis, monitoring the course of disease and results of treatment. MATERIAL
      AND METHODS: The study comprised 80 patients diagnosed and treated for neoplasm
      of the eye. The study group included 48 girls and 32 boys aged 2 weeks to 18
      years. All the patients were subject to full ophthalmologic examination,
      ultrasound and other imaging techniques. RESULTS: Echogenicity of lesions,
      focality of growth and the comparison of echostructure did not allow for
      establishing the degree of malignancy. The presence of vessels in tumor mass and
      blood flow in tumors were useful for differentiation between malignant and benign
      tumors. CONCLUSIONS: Ultrasound methods used significantly improve diagnostic
      possibilities in orbital tumors in children. The obtained pictures of vessels and
      flow character are typical for some tumors, which together with histopathology of
      tumors enables establishing of correct diagnosis. CD/PD ultrasound is helpful in
      monitoring treatment of selected orbital tumors, enables evaluation of biological
      evolution of capillary hemangioma and assessment of vascularization degree of
      tumors treated with chemo- and radiotherapy.

PMID- 16416992
TI  - [Central corneal thickness measurements in children].
AB  - PURPOSE: To evaluate central corneal thickness in children. MATERIAL AND METHODS:
      Central corneal thickness was measured with the use of ultrasound pachymeter in
      360 children aged 0-14 years. RESULTS: Mean central corneal thickness was 537
      microm after the birth and 567 microm in the age of 14 years. Wide differences
      between minimum and maximum recorded values were observed (410-650 microm) in
      first 2 years of life, and 420-640 microm in years 2-14. CONCLUSIONS: 1. Mean
      central corneal thickness in children (even in small one's) does not differ
      significantly from adults and does not change with age. 2. Great differences
      between minimum and maximum recorded values were observed in children (especially
      in first two years of life), exceeding the range in adults. 3. IOP measurements
      in children should be corrected according to the results of central corneal
      thickness.

PMID- 16416993
TI  - [Central corneal thickness in children with congenital glaucoma].
AB  - PURPOSE: To evaluate central corneal thickness in children with congenital
      glaucoma. MATERIAL AND METHODS: Central corneal thickness was measured with the
      use of ultrasound pachymeter in 49 eyes of 30 children, with congenital glaucoma
      aged 0-12 years. RESULTS: Mean central corneal thickness was 462 microm. Very
      wide differences between minimum and maximum recorded values were observed (380
      780 microm). Three groups of patients could be distinguished: with very thin
      cornea of 380-450 microm (73% children), with normal corneal thickness of about
      550 microm (15%) and with very thick cornea of 680-780 microm (12% patients).
      CONCLUSIONS: 1. Mean central corneal thickness in children with congenital
      glaucoma is significantly thinner than in healthy children in the same age and in
      adult patients with glaucoma. A very wide differences between minimum and maximum
      recorded values, are observed in these patients. 2. The results of applanation
      tonometric measurements are underestimated in most cases or less frequently
      overestimated. 3. The measurements of central corneal thickness should be
      performed in every patient with congenital glaucoma to correct the IOP values.

PMID- 16416994
TI  - [Corneal endothelial density in glaucoma patients].
AB  - PURPOSE: To asses mean endothelial cell density in glaucoma patients. MATERIAL
      AND METHODS: Examinations were conducted and registered using the Noncon Robo
      (Konan) non-contact specular microscope between years 2000 and 2004, in Tadeusz
      Krwawicz Chair of Ophthalmology and 1st Eye Hospital, Medical University of
      Lublin. The results of 159 patients (233 eyes) with glaucoma and 37 patients (44
      eyes) with pseudoexfoliation syndrome were analyzed. Patients, 22-91 years old,
      were divided into 8 groups according to the clinical diagnosis and for each group
      an adequate control group was matched. Statistical analysis was carried out to
      compare the examined and control groups using the non-parametric U Mann-Whitney
      test. RESULTS: Corneal endothelial cell density were significantly lower in all
      groups of glaucoma patients. There was a significant reduction in cell count in
      patients with chronic angle-closure glaucoma: 2333 +/- 476/mm2, control group
      (C): 2809 +/- 378/mm2, p< 0.001), acute angle-closure glaucoma 2136 +/- 620/mm2,
      C. 2780 +/- 384/mm2, p< 0.001, pigmentary glaucoma 2537 +/- 355/mm2, C. 3003 +/-
      335/mm2, p< 0.05, juvenile glaucoma 2337 +/- 277/mm2, C. 3001 +/- 168/mm2, p<
      0.001, primary open angle glaucoma 2326 +/- 231/mm2, C. 2779 +/- 398/mm2, p<
      0.001, normal tension glaucoma 2343 +/- 394/mm2, C. 2732 +/- 356/mm2, p< 0.01,
      capsular glaucoma 2128 +/- 483/mm2, C. 2753 +/- 354/mm2, p< 0.001 and in patients
      with pseudoexfoliation syndrome 2255 +/- 299/mm2, C. 2721 +/- 352/mm2, p< 0.001.
      CONCLUSIONS: Patients with glaucoma have lower mean corneal endothelial cell
      density than control groups. The density of corneal endothelial cells depends on
      the type of glaucoma.

PMID- 16416995
TI  - [Objective retinal nerve fiber laser assessment by scanning laser polarimetry in
      patients with chiasmal compression].
AB  - PURPOSE: To assess the evaluation ability of retinal nerve fiber layer (RNFL) in
      patients with visual tracts' compression and to assess the correlation between
      visual field loss and changes in RNFL. MATERIAL AND METHODS: Polarimetric RNFL
      analysis (scanning laser polarimeter- NFA/GDx, software version 1.0.16, LDT(inc))
      and kinetic perimetry were done in 41 eyes with different types of optic chiasma
      compression and in 40 healthy eyes, age matched controls. RESULTS: In eyes with
      optic chiasma compression most of the GDx parameters were statistically different
      from the control group (P<0.05). In eyes with normal visual fields and with optic
      chiasma compression most of GDx parameters were statistically different from the
      other analyzed groups. CONCLUSIONS: GDx may be a helpful tool in diagnosis of
      optic chiasma diseases. GDx is a useful visual prognostic indicator in the
      preoperative assessment of optic chiasma compression. Objective RNFL assessment
      is especially important in patients with serious visual field loss and poor
      visual acuity.

PMID- 16416996
TI  - [Surgical treatment of lens dislocation in children--analysis of complications].
AB  - PURPOSE: To present the surgical complications in eyes with ectopia lentis in
      children. MATERIAL AND METHODS: 116 eyes of 65 children were operatively treated
      for lens dislocation. Pars plana lensectomy, vitrectomy and IOL implantation with
      scleral fixation were done in all eyes. Time of observation ranged between 1-6
      years (mean 3.4). RESULTS: There were no serious intraoperative complication
      (mainly hemorrhage to anterior and posterior chamber). Postoperative
      complications included retinal detachement in 3 (2.6%) eyes and endophthalmitis
      in 1 (0.8%) eye, were the major complications observed in all patients.
      Complications related to scleral fixation included exposure of the scleral
      fixation suture in 8 (6.9%) eyes, lens decentration in 9 (7.8%) eyes, pupil
      capture in 3 (2.6%). CONCLUSIONS: The surgical procedure is useful and safe in
      the management of subluxated lenses in children.

PMID- 16416997
TI  - [The estimation of functional results after surgical treatment for ectopia lentis
      in children].
AB  - PURPOSE: To review the visual outcome of planned pars plana lensectomy and
      vitrectomy with posterior chamber intraocular lens implantation for ectopia
      lentis in children. MATERIAL AND METHODS: Between 1997-2002, 116 eyes were
      operated because of lens subluxation, mainly because of decreased visual acuity
      (<0.4). Lens subluxation was associated with homocystinuria in 4 patients (8
      eyes), Marfan's syndrome in 30 (54 eyes), congenital simple ectopia lentis in 16
      (31 eyes), post trauma in 6 (6 eyes), and congenital ectopia lentis and pupillae
      in 9 (17 eyes). Time of observation ranged between 1 to 6 years (mean 3.4).
      RESULTS: After surgery, we achieved best-corrected visual acuity improvement in
      89%. Unsatisfactory visual results were due to amblyopia (9 eyes), complications
      of retinal detachement surgery (3 eyes), uveitis (2 eyes), glaucoma (1 eye).
      CONCLUSIONS: Pars plana lensectomy, vitrectomy and scleral-fixated IOL
      implantation give quick and good functional results. To achieve these results,
      visual rehabilitation and amblyopia treatment is necessary.

PMID- 16416998
TI  - [Changes of eye refraction, corneal power and lens power during growth in
      emmetropia, myopia and hyperopia].
AB  - PURPOSE: The aim of this study was to evaluate changes of eye refraction, corneal
      power and lens power during growth in emmetropia, myopia and hyperopia. MATERIAL
      AND METHODS: We examined 183 children (363 eyes) aged 4 to 19 with emmetropia,
      myopia and hyperopia. All measurements were performed after cycloplegia with 1%
      tropicamidum. Total refraction and corneal power was examined with
      autokeratorefractometer. Then we used ultrasound biometer Ocuscan (Alcon, USA),
      to measure axial length of the eye. Lens power was calculated with use of SRK II
      formula. RESULTS AND CONCLUSIONS: Mean refractive error in whole group in the age
      of 4 was +2,86D and was gradually decreasing to reach OD in the age of 14.
      Between 4th and 14th years old, myopia increases slowly and then acceleration of
      this process was observed. In hyperopic eyes between 4th and 16th years old,
      refractive error decreases gradually and then stabilization was noted. Mean
      corneal power between 4th and 19th years old, decreased in emmetropia and myopia
      by 1.24D and 2.19D respectively, and increased by 0.38D in children with
      hyperopia. This changes took place before 10th years old. Mean lens power between
      4th and 19th years old, decreased in emmetropia by 2.01 D, in myopia by 1.43D and
      in hyperopia by 1.78D. This changes took place before 12th years old.

PMID- 16416999
TI  - [Frequency and incidence of myopia among medical students].
AB  - PURPOSE: To estimate the frequency and dynamic changes in refractive errors in
      population of students of medical (MF) and dental (DF) faculties of Pommeranian
      Medical Academy in Szczecin. MATERIAL AND METHODS: Medical records from
      ophthalmic examinations performed in 176 medical students (117 females and 59
      males) during the 2nd and 4th course of studies were analyzed (2-years long
      observation). RESULTS: Refractive error was found in 42% of MF students and 39.5%
      of DF students on the 2nd course and in 51% and 47% on the 4th course
      respectively. Myopia was found in 75% of ametropic eyes. In 2 years observation
      time, there was a statistically significant progression of refracive error in 50%
      of myopic students (from -2.9 +/- 2.3 D to -3.4 +/- 1.9D in MF and from -2.0 +/-
      1.5 to -2.4 +/- 1.5D in DF). Myopia developed in 13% of initially emmetropic
      students.

PMID- 16417000
TI  - [The relation between the clinical state of the premature and the development of
      3rd stage of retinopathy of prematurity].
AB  - The aim of the study was to determine the prognostic value of some pathologies
      related to prematurity in the development of stage 3 ROP in children with
      extremely low birth-weight. The group of 35 prematures with diagnosed 3rd stage
      ROP and 64 prematures without ROP was examined. The presence of the respiratory
      distress syndrome (RDS), persistent ductus arteriosus (PDA), necrotizing
      enterocolitis (NEC) and intraventricular haemorrhages (IVH) were analyzed. RDS
      was more frequent in prematures with 3rd stage ROP (p=0.005, OR=3.59). There was
      significant difference between the frequency of IVH in both groups (p = 0.03),
      but the odds ratio was significantly high only in the children with the 3rd stage
      IVH (OR=2.42). PDA was diagnosed more frequently in children with 3rd stage ROP
      but the difference was not statistically significant (p= 0.1 52, OR=1.80). There
      was significant difference between the groups when comparing the incidence of NEC
      (p=0.03, OR=3.34). The pathologies of the prematurity such as RDS, NEC and grade
      III IVH are the predictive factors for the development of stage 3 ROP (p=0.03,
      OR=3.34).

PMID- 16417001
TI  - [Tumors and tumor-like lesions of eyelids collected at Department of Pathological
      Anatomy, Wroclaw Medical University, between 1946 and 1999].
AB  - PURPOSE: To determine the histopathological, epidemiological and clinical
      characteristics of benign, malignant and tumor-like lesions of the eyelid
      collected in Department of Pathological Anatomy, Wroclaw Medical University.
      MATERIAL AND METHODS: Department of Pathological Anatomy, Wroclaw Medical
      University, has been collecting data of all tumors and tumor-like lesions of the
      eye and ocular adnexa diagnosed at the department during the 54-year interval
      from 1946 through 1999. Retrospective analysis of all eyelid biopsy specimens
      submitted to the department between January 1, 1946, and December 31, 1999 were
      performed. RESULTS: There were 4818 cases of the eye and ocular adnexa lesions
      diagnosed at the department since 1946 and 1999, what made up 0.262% of all
      diagnosed cases. Of 4818 total number of cases there were 2416 women and 2392
      men. In 10 cases sex was unknown. The eyelids were the most common localization
      of malignant tumors (39.9% cases of all eye regions). The incidence cohort of all
      eyelid lesions included 2031 cases what made up 42.15% of all diagnosed lesions
      within the eye and it's adnexa. Benign tumors were the most common lesions
      (n=1262; 62.2%). Among all them papillomas were the most commonly found (n=659;
      52.3%). Malignant tumors constituted 21,3% (n=433). Of the 433 malignancies, 314
      were basal cell carcinomas (72.5%). Malignant tumors developed most commonly on
      the lower eyelid (n=303; 70%) but involved the right and left sides with equal
      frequency. Almost 2/3 of all tumor-like lesions in both genders were cysts
      including atheromas. CONCLUSIONS: Benign eyelid tumors compose the majority of
      all eyelid lesions. The eyelids are the most common localization of malignant
      tumors within the eye and it's adnexa. Basal cell carcinoma is the most common
      malignant eyelid tumor. The lower eyelid is the most frequent site of origin in
      cases of malignant tumors. Men and women are equally affected.

PMID- 16417002
TI  - [Tear film profile in patients with active thyroid orbithopathy].
AB  - Dry eye symptoms and tear film profile were examined in 21 patients with Graves'
      disease complicated by active thyroid orbitopathy (OT). Dry eye symptoms and
      clinical tests: break-up time (BUT), Schirmer I, fluorescein and lissamine green
      staining in OT patients, were comparable with control group. Dry eye symptoms
      were present in 85% of OT patients compared with 30% in control group. BUT (5.84
      +/- 3,31sec.) and Schirmer test (11.11 +/- 9,14mm) were significantly lower when
      compared with control group (11.4 +/- 3,75sec and 20.5 +/- 9,65mm). Lissamin
      green staining intensity score (3.61 +/- 1,74) as well as positive fluorescein
      staining in OT patients, were significantly higher when compared with control.

PMID- 16417003
TI  - [The usefulness of thermography in the diagnostics of dry eye syndrome].
AB  - PURPOSE: The aim of the study was to evaluate corneal temperature in patients
      with dry eye syndrome, and in normal subjects by measuring with infrared
      radiation thermography. MATERIAL AND METHODS: Each eye of 9 patients with dry eye
      syndrome and each eye of 13 normal subjects, were evaluated in this study. The
      corneal surface temperature was measured during 15 seconds after opening the eye.
      RESULTS: Mean corneal temperature was lower in the dry eye syndrome patients
      compared with the control group. Decrease in time of mean corneal temperature in
      patients with dry eye syndrome, was lesser than in the control group.
      CONCLUSIONS: The study shows the usefulness of thermography in the diagnosis of
      dry eye syndrome.

PMID- 16417004
TI  - [Mono- and multislice computed tomography of the orbita injury].
AB  - PURPOSE: To evaluate the reliability of the mono- (SCT) and multisliced CT (MSCT)
      imaging and their post-processing reconstructions in the cases of orbital trauma.
      MATERIAL AND METHODS: the spiral monoslice (n=20) and spiral multisliced (n=5) CT
      studies were performed in patients suffered from orbits' injuries. CT data were
      reconstructed in the 2D and 3D mode. The CT original images and the 2D and 3D
      reconstructions were evaluated according to the quality of visualization of a
      pathological lesions. Surgery was the method of reference. RESULTS: The
      reconstructed 3D images in 16 patients examined in SCT mode and in 5 patients
      examined in MSCT mode allowed to recognize properly the fracture. In the 13
      patients SCT and in the 3 ones MSCT revealed the bone fragments and orbital soft
      tissues prolapse towards maxilla sinus; including the lower rectus muscle in 6
      cases. In 1 patient evaluation of the 3D model allowed to exclude communication
      with intracranial space. The surgery correlated well with the source images and
      2D/3D SCT and MSCT models. The diagnostic quality of the raw SCT vs MSCT images
      was evaluated as equal, but MSCT proved to be the better source for the post
      processing reconstruction, because of higher resolution and better smoothing.
      CONCLUSIONS: - Spiral CT 2D and 3D reconstructed images, especially generated
      from the MSCT, more clearly than the source data depict anatomical spatial
      relationships; - 2D/3D reconstructions revealed the position, course and
      displacement of a fractured fragments; thus it supports the surgery.

PMID- 16417006
TI  - [The picture of visual evoked potentials in type 2 diabetes mellitus].
AB  - The aim of this study was to assess frequency of abnormal visual evoked
      potentials in type 2 diabetic patients and the correlation between patients' age,
      duration of the disease, metabolic control and coexisting clinical complications
      on the abnormal recordings. 41 diabetic patients, aged 35 to 62 years were
      examined. The VEP recordings were performed four times, each time using a pattern
      made up of elements of another size (18, 36, 72 and 144 angular minutes). With
      this method the abnormal VEP were recorded in 22% of the cases. The abnormal VEP
      recordings with a single size pattern were in 8% to 14% of the cases. The P100
      latency increased in 33% of the pathological recordings and in about 66% of the
      cases there was a significant difference between the latencies from both eyes.
      There was no statistically significant correlation between the age, duration of
      the disease, coexisting clinical complications or metabolic compensation and the
      abnormal recordings.

PMID- 16417005
TI  - [The picture of visual evoked potentials in type 1 diabetes mellitus].
AB  - The aim of this study was to assess frequency of abnormal visual evoked
      potentials in type 1 diabetic patients and the correlation between patients' age,
      duration of the disease, metabolic control and coexisting clinical complications
      on the abnormal recordings. The investigation was carried out in a group of 50
      diabetic patients, aged from 16 to 55 years. The VEP recordings were performed
      four times, each time using a pattern made up of elements of another size (18,
      36, 72 and 144 angular minutes). With this method the abnormal VEP were recorded
      in 26% of the cases and it was possible to find 10% patients who had more than
      one abnormal test. In VEP recorded with stimulation with a single size pattern,
      abnormal results were recorded from 8% to 14% of the cases. The pathological VEP
      were recorded as elongation of P100 latency in 86% type 1 diabetic patients, and
      as significant difference between the latencies from both eyes in 14% cases.
      There was no statistically significant correlation between the age, duration of
      the disease, coexisting clinical complications or metabolic compensation and the
      abnormal recordings.

PMID- 16417007
TI  - [Ocular manifestations in bone marrow transplantation--case report].
AB  - We present two cases of patients who developed keratitis sicca (dry eyes) and
      pemphigoid-like symptoms after allogeneic bone marrow transplantation. Skin
      biopsy revealed changes typical of GVHD. In both cases immunosuppressive
      treatment, systemic and local, produced improvement of the clinical condition.

PMID- 16417008
TI  - [Progression of diabetic retinopathy in patient with Graves' disease].
AB  - The authors present the case of 16-year old girl with diabetes mellitus type 1.
      She had progression of diabetic retinopathy because of occurrence of Graves'
      disease. Surgical intervention (strumectomy subtotal, bilateral), was performed
      and regression of retinal changes was observed.

PMID- 16417009
TI  - Dry eye syndrome and cataract as ocular manifestations of Crohn's disease.
AB  - PURPOSE: Crohn's disease is disorder classified under inflammatory bowel disease.
      Apart from the classic features of the inflamed bowel, patients may develop
      widespread systemic manifestations, including ocular changes. The authors present
      a case of ocular complaints in patient with Crohn's disease. MATERIAL AND
      METHODS: Case report of 11-year-old girl with Crohn's disease. We perform
      complete ophthalmologic examination and dry eye syndrome tests. RESULTS: A female
      patient with symptoms of dry eye syndrome and cataract in the both eyes was
      reported. CONCLUSIONS: Crohn's disease may be associated with ocular findings,
      such dry eye syndrome and cataract. Evaluation of the eye should be a routine
      component in the care of patients with Crohn's disease.

PMID- 16417010
TI  - [The Vogt-Koyanagi-Harada syndrome in 11-year-old girl].
AB  - PURPOSE: The Vogt-Koyanagi-Harada syndrome is an idiopathic, multisystem disorder
      which typically affects pigmented individuals between 20-50 years old. The
      typical symptoms include granulomatous panuveitis with characteristic extraocular
      dermato-neurological manifestations. The case of VKH syndrome affecting Polish
      girl is very rare. CASE REPORT: A 11-year-old girl had an important decrease of
      visual acuity in both eyes (RE 0.1 and LE 0.2), with the presence of bullous
      serous retinal detachment in both eyes. Besides, in right eye some keratic
      precipitates were noted. The routine laboratory evaluation failed to provide a
      diagnosis. The patient was treated with an intravenous bolus of corticosteroid
      therapy and then, high dose of oral prednisone. RESULTS: After administered
      therapy the visual acuity improved rapidly in both eyes (RE 1.0 and LR 0.9), and
      the exudative retinal detachment resolved. After 5 months, the patient's
      examination showed a sunset glow fundus with several whitish rounded lesions in
      peripheral fundus, which is typical for the VKH syndrome. CONCLUSIONS: The VKH
      syndrome rarely affects young children, so the diagnosis may be difficult in the
      absence of the typical extraocular manifestations. In such atypical cases the
      diagnosis is based on the clinical evolution of the disease.

PMID- 16417011
TI  - [Ocular complications in course of idiopathic retroperitoneal fibrosis].
AB  - Idiopathic retroperitoneal fibrosis is a rare collagen vascular disease of still
      unclear, immunological etiology. One of the first descriptions of this pathology
      was derived from Ormond and the Ormond's disease became its second name. It is
      characterized by a chronic, non-specific inflammation of the retroperitoneum,
      which obstructs retroperitoneal structures. The most frequent complication is the
      ureteric obstruction with hydronephrosis and renal failure. The fibrotic process
      may develop in different, even remote sites, including ophthalmic system. We have
      presented a 50-year-old woman with Ormond's disease and anterior uveitis. We have
      also described the other ocular complications of this disease.

PMID- 16417012
TI  - [Intraorbital foreign body--three years follow-up].
AB  - A case of patient with metallic intraorbital foreign body, was described. The
      foreign body went trough the eye and finally was situated close to the optic
      nerve. After three years, no signs of siderosis were found (ERG). The patient is
      still under control.

PMID- 16417013
TI  - [Local involvement of the optic nerve by acute lymphoblastic leukemia].
AB  - The leucemias quite commonly involve the eyes and adnexa. In some cases it causes
      visual complants. Both, the anterior chamber of the eye and the posterior portion
      of the globe may sites of acute or chronic leukemia and leucemic relapse. We
      report an unique case of a 14 years old leucemic patient who suffered visual loss
      and papilloedema, due to a unilateral local involvement within optic nerve,
      during second relapse of acute lymphocytic leuemia. In spite of typical treatment
      of main disease, the boy had died. The authors present typical ophthalmic
      features of the leucemia, too.

PMID- 16417014
TI  - [Present views concerning surgery treatment of keratoconus].
AB  - Keratoconus is a noninflammatory, progressive disease with ectasia and thinning
      of the corneal stroma, leading to decrease visual acuity related to asymmetrical
      irregular astigmatism and myopia. Currently, patients with keratoconus who are
      contact lens intolerant, are primarily treated by penetrating keratoplasty. When
      the cornea is transparent, other options may be considered. There are several
      studies about intrastromal rings implantation, in eyes with keratoconus. The
      major objective of corneal ring implantation is to reshape the abnormal cornea
      without removing corneal tissue or touching the central cornea.

PMID- 16417015
TI  - [Choroidal detachment--pathogenesis, etiology and clinical features].
AB  - Serous choroidal detachment is characterized by exudative detachment of the
      retina and choroid following leakage of fluid from the choriocapillaris into
      suprachoroidal space. This accumulation of fluid has been known to be a
      complication of various intraocular surgeries (cataract, glaucoma and retinal
      detachment surgery), where hypotony is combined with postoperative inflammation.
      Among other non surgical conditions associated with uveal effusion are idiopathic
      (uveal effusion syndrome, microphthalmia) and inflammatory diseases (scleritis,
      sympathic ophthalmia, pars planitis, Harada's disease). Idiopathic serous
      detachment of choroids is caused by scleral abnormalities associated with
      hypoplasia or partial absence of the vortex venous system. The most cases of
      postoperative choroidal detachment resolve spontaneously. Resolution is usually
      associated with rapid normalization of the intraocular pressure and reduction of
      intraocular inflammation. The natural course of idiopathic condition is variable
      but tends to be prolonged with remissions and exacerbations. Surgical management
      involving vortex vein decompression and/or sclerotomy is the most effective
      treatment in this patients.

PMID- 16417016
TI  - [Role of nitric oxide in ophthalmic diseases].
AB  - Nitric oxide is a unique molecule with simple chemical structure and
      sophisticated and heterogeneous functions in human organism. In this article, we
      reviewed possible participations of nitric oxide in physiological and
      pathological states inside the eye (eg. glaucoma, cataract, uveitis and retinal
      disorders).

PMID- 16417017
TI  - [The role of the oxidative mechanisms in the pathogenesis of age related macular
      degeneration].
AB  - Oxidative stress, are believed to be an important factor in the pathogenesis of
      age related diseases e.g. age related macular degeneration (AMD) and age related
      cataract. The is strong evidence suggesting that antioxidants can protect against
      development of this diseases, how ether experimental and clinical data have often
      been inconsistent. In this paper authors presents the review of the literature
      concerning on the connections between oxidative mechanisms and AMD and protective
      role of the antioxidative vitamin and other antioxidative factors supplementation
      in this disorder. This publication tries to estimate the anti-pericyte
      autoantibodies role in progression of diabetic retinopathy.

PMID- 16417018
TI  - [The role of anti-pericyte antibodies in the development of diabetic
      retinopathy].
AB  - Diabetic retinopathy is one of the most common devastating complications of
      diabetes. Pericyte loss, microaneurysms and acellular capillaries are
      characteristic for the diabetic retina. Researches have provided evidence that
      hyperglycaemia is one of the main factors driving the onset and progression of
      diabetic retinopathy. Although it has been shown that tight metabolic control has
      beneficial effects on the development and progression of this complication, the
      increase of blood glucose concentrations does not account for all the risk for
      development and progression to sight threatening retinopathy. A number of reports
      suggest that autoimmune mechanism play a role in diabetic microangiopathy
      (circulating antiendothelial cells autoantibodies, antiphospholipid antibodies,
      presence of immunoglobulins, lymphocytes and cytokines in diabetic retinal
      tissue). Diabetic subjects were also found to have autoantibodies to
      microvascular pericytes in their circulation. These results may contribute to
      understanding why retinopathy progresses in some patients, despite consistent
      reduction of blood sugar. This publication tries to estimate the anti-pericyte
      autoantibodies role in progression of diabetic retinopathy.

PMID- 16417019
TI  - [Fundus autofluorescence examination using a confocal scanning laser
      ophthalmoscope HRA (Heidelberg Retina Angiograph)].
AB  - PURPOSE: To present application of a confocal Scanning Laser Ophthalmoscope
      (cSLO) for fundus autofluorescence examination, as a new method of visualization
      of retinal pigment epithelium and its possible significance in the diagnosis of
      different retinal diseases. MATERIAL AND METHODS: Typical autofluorescence images
      in age-related macular degeneration (AMD), Stargardt disease, Best disease and
      pattern dystrophies are presented, based on the own experience and literature
      data. Autofluorescence images were obtained with a cSLO using an argon laser for
      generation of excitation light at 488 nm and a barrier filter >500 nm for the
      detection of the emitted signals. RESULTS: A variety of autofluorescence
      patterns, associated with the accumulation of lipofuscin in RPE cells, was found
      in the above entities. CONCLUSIONS: Presented method of fundus autofluorescence
      examination gives new possibilities in studying the pathogenetic mechanisms in
      various retinal diseases and may be useful in monitoring the follow-up and the
      effects of the treatment.

PMID- 16417020
TI  - [Neuronal and hormonal regulatory mechanisms of tears production and secretion].
AB  - The ocular surface, tear film, lacrimal glands act as a functional unit to
      preserve the quality of the refractive surface of the eye, and to resist injury
      and protect the eye against bodily and environmental conditions. Homeostasis of
      this functional unit involves neuronal and hormonal regulatory mechanisms. The
      eye appears to be a target organ for sex hormones particulary the androgen, as
      they modulate the immune system and trophic functions of the lacrimal and
      Meibomian glands.

PMID- 16417021
TI  - [Immunological aspects of tear fluid].
AB  - The eye is linked to the common mucosal immune system. This system play the part
      in preservation of the ocular surface. Tear fluid contains pro and anty
      inflammatory factors such as lactoferrin, plasmin, immunoglobulins, and a lot of
      cytokines (interleukins, GM-CSF, TGF alfa and beta). The cornea is immunologicaly
      preferred, as a result of lack of resident lymphoreticular cells.

PMID- 16417022
TI  - [Is it possible to diagnose lymphoproliferative lesions by fine needle aspiration
      biopsy?].
AB  - Despite the fact that fine needle aspiration biopsy (FNAB) is a commonly employed
      method in modern oncological diagnostic management, it has found no extensive use
      to diagnose lymphoproliferative lesions of the orbit and eye adnexa. Benign and
      malignant lymphoproliferative lesions and pseudotumor have a very similar
      clinical course. Microscopicaly, the lesions are also similar and hence even on
      histology it is difficult to differentiate between these conditions based on the
      morphology. We believed, that routine cytology and flow cytometry and/or PCR
      method in materials obtained in the course of FNAB are fast and sensitive methods
      and in many cases allow to avoid a surgical biopsy.

PMID- 16417023
TI  - [Ophthalmic manifestations of Turner's syndrome].
AB  - Authors present pathogenesis, clinical manifestations, ocular findings, diagnosis
      and treatment of patients with Turner's syndrome.

PMID- 16417024
TI  - [Visual system involvement in selected zoontic diseases. III. Cysticercosis T.
      solium].
AB  - Cysticercosis of visual system is a serious clinical problem. Cysticercosis
      (cysticercus cellulose) may cause damage to different structures of this system,
      leading sometimes to dangerous consequences (phthisis and total blindness).
      Involvement of visual system may coexist with cysticercosis of central nervous
      system. In current paper we present parasytologic and epidemiologic aspects, as
      well as clinical pathology of T. solium cysticercosis with special attention
      directed to lesions within visual system. Current laboratory methods (immuno- and
      radiologic) indispensable for diagnosis of cysticercosis, as well as outline of
      therapy (pharmacological and surgical), are also presented.

PMID- 16417025
TI  - [Jacques Daviel--the inventor of the extracapsular cataract extraction surgery].
AB  - On April 8, 1747, Jacques Daviel called to operate on M. Garion, a master
      wigmaker, whose cataracts appeared very favorable for surgery. Nevertheless, the
      expert Daviel was unable to depress lens. At that moment, he decided on a
      deliberate extraction. After widely opening the right cornea, he passed a small
      spatula through the pupil and extracted from the posterior chamber the lens. Thus
      was initiated the first significant advance in cataract surgery since the
      invention of couching in ancient India.

PMID- 16417026
TI  - [Report about the activity of the Department and Ophthalmological Clinic of the
      Medical Academy in Slansk in Katowice].

PMID- 16417027
TI  - [Report from the Second Symposium of the Military Ophthalmological Section in
      Poland].

PMID- 16417028
TI  - Air, hair, knees, nose.

PMID- 16417029
TI  - Preoperative low molecular weight heparin as venous thromboembolism prophylaxis
      in patients at risk for prosthetic infection after knee arthroplasty.
AB  - OBJECTIVE: To investigate the effect of preoperative initiation of low molecular
      weight heparin as prophylaxis for deep venous thrombosis in patients at risk of
      developing surgical-site infections after knee arthroplasty. DESIGN: Case-control
      study nested in a cohort. The incidence of surgical-site infection in the cohort
      was calculated. With the use of data extracted from medical histories and after
      adjustment for other risk factors, the effect of preoperative heparinization on
      the risk of incisional and prosthetic infection among case-patients and control
      patients (1:3 ratio) was assessed. SETTING: Orthopedic department in a tertiary
      care referral hospital. PATIENTS: A cohort of 160 consecutive patients who had
      received prosthetic knee implants between October 1, 2001, and November 30, 2003.
      RESULTS: Eighteen patients with surgical-site infections were identified,
      yielding an incidence of incisional and prosthetic infection of 6.9 (95%
      confidence interval [CI95], 3.5 to 12.0) and 4.4 (CI95, 1.8 to 8.8) cases per 100
      patients undergoing surgery, respectively. Surgical-site infection was associated
      with preoperative use of low molecular weight heparin (odds ratio [OR], 6.2 after
      adjustment for medical and surgical factors; CI95 1.5 to 23). Prosthetic
      infection was strongly associated with preoperative use of prophylaxis (OR,
      undetermined [100% exposure in case-patients vs 35% exposure in control
      patients]; P = .002), but incisional surgical-site infection was not. CONCLUSION:
      The use of low molecular weight heparins immediately before knee arthroplasty as
      prophylaxis for deep venous thrombosis should be questioned because of probable
      increased risk of prosthetic infection.

PMID- 16417030
TI  - Infection control practices to reduce airborne bacteria during total knee
      replacement: a hospital survey in four states.
AB  - OBJECTIVE: To describe the use of laminar airflow, body exhaust, and ultraviolet
      lights during total knee replacement (TKR) in four U.S. states. DESIGN: Survey of
      healthcare facilities. SETTING: Hospitals in Illinois, North Carolina, Ohio, and
      Tennessee that performed TKR during 2000 as identified by Medicare claims data.
      PARTICIPANTS: Hospitals responding to a mailed questionnaire. RESULTS: Two
      hundred ninety-five (73%) of 405 eligible hospitals that performed 18,374 primary
      and revision TKR procedures responded to the questionnaire. Among responding
      hospitals, 30% reported regular use (for > 75% of procedures) of laminar airflow,
      42% reported regular use of body exhaust, and 5% reported regular use of
      ultraviolet lights. Among hospitals providing complete data, 150 (58%) performing
      66% of procedures reported regular use of at least one of these techniques. On
      regression analyses, laminar airflow was used more often by hospitals with a TKR
      volume greater than 25 procedures per year (odds ratio [OR], 2.0; 95% confidence
      interval [CI95], 1.1-3.7) and orthopedic residency programs (OR, 2.8; CI95, 1.3
      6.3), but its use was not significantly related to hospital setting or ownership
      status. CONCLUSIONS: Although these clean air practices are not recommended by
      any U.S. governmental or professional organization, they are used in nearly two
      thirds of TKR procedures. Better information about their impact on current
      practice and more explicit guidelines may aid decisions about the use of these
      resource-intensive infection control practices.

PMID- 16417031
TI  - Perioperative intranasal mupirocin for the prevention of surgical-site
      infections: systematic review of the literature and meta-analysis.
AB  - OBJECTIVE: To review the evidence evaluating perioperative intranasal mupirocin
      for the prevention of surgical-site infections according to type of surgical
      procedure. DESIGN: Systematic review and meta-analysis of published clinical
      trials. SETTING: Studies included were either randomized clinical trial or
      prospective trials at a single institution that measured outcomes both before and
      after an institution-wide intervention (before-after trial). In all studies,
      intervention and control groups differed only by the use of perioperative
      intranasal mupirocin in the intervention group. PATIENTS: Patients undergoing
      general or nongeneral surgery (eg, cardiothoracic surgery, orthopedic surgery,
      and neurosurgery). MAIN OUTCOME MEASURE: Risk of surgical-site infection
      following perioperative intranasal mupirocin versus usual care. RESULTS: Three
      randomized and four before-after trials met the inclusion criteria. No reduction
      in surgical-site infection rate was seen in randomized general surgery trials
      (summary estimates: 8.4% in the mupirocin group and 8.1% in the control group;
      relative risk [RR], 1.04; 95% confidence interval [CI95], 0.81 to 1.33). In
      nongeneral surgery, the use of mupirocin was associated with a reduction in
      surgical-site infection in randomized trials (summary estimates: 6.0% in the
      mupirocin group and 7.6% in the control group; RR, 0.80; CI95, 0.58 to 1.10) and
      in before-after trials (summary estimates: 1.7% in the mupirocin group and 4.1%
      in the control group; RR, 0.40; CI95, 0.29 to 0.56). CONCLUSIONS: Perioperative
      intranasal mupirocin appears to decrease the incidence of surgical-site infection
      when used as prophylaxis in nongeneral surgery. Given its low risk and low cost,
      use of perioperative intranasal mupirocin should be considered in these settings.

PMID- 16417032
TI  - Hair removal policies in clean surgery: systematic review of randomized,
      controlled trials.
AB  - OBJECTIVE: To determine whether certain hair removal policies are better than
      others to prevent surgical-site infections in patients undergoing clean surgery.
      METHODS: Publications were retrieved by a systematic search of Medline, the
      Cochrane Library, and EMBASE up to February 2005. Additionally, the reference
      lists of all identified trials were examined. All randomized trials, quasi
      randomized trials, and systematic reviews or meta-analyses of randomized or quasi
      randomized trials comparing hair removal policies in clean surgery were selected.
      Trials involving patients undergoing cranial neurosurgery were excluded. Two
      reviewers independently assessed trial quality and extracted data. Disagreements
      were resolved by discussion with a third reviewer. Data from the original
      publications were used to calculate the relative risk or risk difference of
      surgical-site infection. Data for similar outcomes were combined in the analysis,
      where appropriate, with the use of a random effects model. RESULTS: Four trials
      were included in the review. No eligible systematic review or meta-analysis of
      randomized or quasi-randomized trials was found. The quality of the trials and
      how they were reported were generally unsatisfactory. Evidence regarding whether
      preoperative hair removal has any effect was inconclusive. When hair removal was
      considered necessary, evidence about the best time for removal was inconclusive.
      There was some evidence that hair removal by clipper is superior to removal by
      razor. CONCLUSIONS: Because of insufficient evidence as a basis for
      recommendations, the practical consequences for ward management were essential
      when the Dutch Working Party on Infection Prevention formulated its
      recommendations for hair removal policies. Large randomized, controlled trials
      are needed to determine the optimal policy for preoperative hair removal.

PMID- 16417033
TI  - Overview: Using mode of action and life stage information to evaluate the human
      relevance of animal toxicity data.
AB  - A complete mode of action human relevance analysis--as distinct from mode of
      action (MOA) analysis alone--depends on robust information on the animal MOA, as
      well as systematic comparison of the animal data with corresponding information
      from humans. In November 2003, the International Life Sciences Institute's Risk
      Science Institute (ILSI RSI) published a 2-year study using animal and human MOA
      information to generate a four-part Human Relevance Framework (HRF) for
      systematic and transparent analysis of MOA data and information. Based mainly on
      non-DNA-reactive carcinogens, the HRF features a "concordance" analysis of MOA
      information from both animal and human sources, with a focus on determining the
      appropriate role for each MOA data set in human risk assessment. With MOA
      information increasingly available for risk assessment purposes, this article
      illustrates the further applicability of the HRF for reproductive, developmental,
      neurologic, and renal endpoints, as well as cancer. Based on qualitative and
      quantitative MOA considerations, the MOA/human relevance analysis also
      contributes to identifying data needs and issues essential for the dose-response
      and exposure assessment steps in the overall risk assessment.

PMID- 16417034
TI  - DNA-reactive carcinogens: mode of action and human cancer hazard.
AB  - It has been known for decades that mutagenicity plays an important role in the
      activity of most carcinogens. This mutagenicity can result from direct damage to
      DNA through a chemical being DNA reactive or from indirect effects, such as
      through the production of oxygen radicals that then react with DNA. This article
      presents a set of key events whereby DNA reactivity initiates the process of
      carcinogenicity that leads to the subsequent mutation induction and enhanced cell
      proliferation that ultimately results in tumor development. This set of key
      events for DNA-reactive chemicals was applied to two case studies (aflatoxin B1
      and dichloromethane) with the aim of assessing the utility of the Human Relevance
      Framework (HRF) for this class of chemicals. The conclusions were that the HRF
      was a viable approach for the use of mechanistic data for DNA-reactive chemicals
      obtained from both laboratory animals and human cells in vivo and in vitro for
      predicting human carcinogenicity. In the case of aflatoxin B1, the HRF could be
      used to predict that carcinogenicity in humans was a likely outcome. In contrast,
      the HRF predicted that the human carcinogenic potential of dichloromethane was at
      best less likely than in rodents; this conclusion was supported by the available
      epidemiological data.

PMID- 16417035
TI  - Mode of action: reduction of testosterone availability--molinate-induced
      inhibition of spermatogenesis.
AB  - Molinate is a preemergent herbicide that has been demonstrated to affect
      reproduction in the rat via alterations in sperm production. A wealth of standard
      toxicological studies and targeted research efforts relating to this adverse
      effect is available, and these were used to evaluate the utility of the Human
      Relevance Framework (HRF) for noncancer health effects. The hypothesized mode of
      action involved inhibition of the hydrolysis of cholesterol from high-density
      lipoprotein in the rat testes, followed by an androgen withdrawal syndrome on
      spermatogenesis. Some evidence is available that a similar mode of action would
      not be operable in humans. Despite the wealth of studies conducted in the rat,
      the weight of evidence is insufficient to define the mode of action for
      reproductive toxicity in the male rat. A principal deficiency in the database was
      discordance between the exposure levels observed to cause biochemical
      disturbances in the testes related to the hypothesized mode of action and the
      dose levels observed to induce the adverse outcome on spermatogenesis. For this
      reason, a complete MOA/human relevance analysis is not possible and, based on
      traditional risk assessment principles, any toxic effects are assumed to be
      relevant for human risk assessment.

PMID- 16417036
TI  - Mode of action: oxalate crystal-induced renal tubule degeneration and glycolic
      acid-induced dysmorphogenesis--renal and developmental effects of ethylene
      glycol.
AB  - Ethylene glycol can cause both renal and developmental toxicity, with metabolism
      playing a key role in the mode of action (MOA) for each form of toxicity. Renal
      toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates
      in the kidney in the form of calcium oxalate crystals and is believed to cause
      physical damage to the renal tubules. The human relevance of the renal toxicity
      of ethylene glycol is indicated by the similarity between animals and humans of
      metabolic pathways, the observation of renal oxalate crystals in toxicity studies
      in experimental animals and human poisonings, and cases of human kidney and
      bladder stones related to dietary oxalates and oxalate precursors. High-dose
      gavage exposures to ethylene glycol also cause axial skeletal defects in rodents
      (but not rabbits), with the intermediary metabolite, glycolic acid, identified as
      the causative agent. However, the mechanism by which glycolic acid perturbs
      development has not been investigated sufficiently to develop a plausible
      hypothesis of mode of action, nor have any cases of ethylene glycol-induced
      developmental effects been reported in humans. Given this, and the variations in
      sensitivity between animal species in response, the relevance to humans of
      ethylene glycol-induced developmental toxicity in animals is unknown at this
      time.

PMID- 16417037
TI  - Mode of action: disruption of brain cell replication, second messenger, and
      neurotransmitter systems during development leading to cognitive dysfunction-
      developmental neurotoxicity of nicotine.
AB  - Developmental exposure to nicotine in rats results in neurobehavioral effects
      such as reduced locomotor and cognitive function. Key events in the animal mode
      of action (MOA) include binding to the nicotinic cholinergic receptor during
      prenatal and/or early postnatal development. This leads to premature onset of
      cell differentiation at the expense of cell replication, which leads to brain
      cell death or structural alterations in regional brain areas. Other events
      include an initial increase followed by a decrease in adenyl cyclase activity, as
      well as effects on the noradrenergic, dopaminergic, and serotonergic
      neurotransmitter systems. Because the nicotine receptor is also present in the
      developing human brain and the underlying biology for DNA synthesis and cell
      signaling is comparable, this MOA is likely to be relevant for humans. Although
      the effects of nicotine exposure in developing humans is not well documented,
      nicotine exposure as a result of cigarette smoking during pregnancy is associated
      with several physiological and behavioral outcomes that are reminiscent of the
      effects of nicotine alone in animal models. As data become available with the
      advent of the use of the nicotine patch in pregnant humans, the question as to
      the relative importance of smoking per se versus nicotine alone may be
      determined.

PMID- 16417038
TI  - Mode of action: impaired fetal leydig cell function--effects on male reproductive
      development produced by certain phthalate esters.
AB  - Certain phthalate esters (di-2-ethylhexyl; di-n-butyl and butyl benzyl) have
      profound effects on the developing male reproductive system when administered
      orally to pregnant experimental animals during a critical window of development.
      These esters produce a syndrome of adverse effects that are characteristic of a
      disturbance in androgen-mediated development and include a variety of
      reproductive tract malformations and effects on developmental phenotypic markers.
      A testicular dysgenesis syndrome has been proposed to explain the secular
      increases in a number of human male reproductive deficits, including decreased
      semen parameters, increased incidence of cryptorchidism and hypospadias (two of
      the most common human birth defects), and increased incidence of testicular (germ
      cell derived) cancer. The rodent phthalate data lend support to the hypothesis.
      This example illustrates a number of points in the use of the Human Relevance
      Framework. First, chemical agents may have more than one mode of action (MOA):
      for example, phthalate-induced peroxisome proliferation leading to
      hepatocarcinogensis, compared with the induction of developmental effects via
      effects on androgen signaling. Second, the case demonstrates the life-stage
      sensitivity of the response to these compounds. Third, because humans may be
      exposed to multiple phthalate esters producing adverse effects on reproductive
      development, these compounds may be useful in testing the utility of the Human
      Relevance Framework (HRF) approach for evaluating cumulative and aggregate risk.

PMID- 16417039
TI  - Mode of action: inhibition of androgen receptor function--vinclozolin-induced
      malformations in reproductive development.
AB  - Vinclozolin is a fungicide that has been shown to cause Leydig cell tumors and
      atrophy of the accessory sex glands in adult rodents. In addition, exposure of
      rats during pregnancy causes a pattern of malformations in the male urogenital
      tract. A wealth of standard toxicological studies and targeted research efforts
      is available related to this adverse effect, and these were used to evaluate the
      Human Relevance Framework (HRF) for noncancer health effects. Vinclozolin and two
      of its metabolites, designated M1 and M2, have been shown to bind and inhibit the
      function of the rat and human androgen receptor. Other means of interfering with
      androgen receptor function (e.g., by exposure to the pharmaceutical agent
      flutamide) lead to similar adverse health outcomes. There is direct in vivo
      evidence in the rat prostate that androgen-dependent gene expression changes
      occur after exposure to vinclozolin. There are no proposed alternatives to the
      androgen receptor-mediated mode of action. Based on what is known about kinetic
      and dynamic factors, confidence is high that the animal mode of action (MOA) for
      vinclozolin-induced malformation of the male reproductive tract is highly
      plausible in humans.

PMID- 16417041
TI  - Mode of action: yolk sac poisoning and impeded histiotrophic nutrition--HBOC
      related congenital malformations.
AB  - Rodents form an early inverted yolk sac placenta (invYSP) by apposing the yolk
      sac to the uterine wall. The invYSP supplies nutrients via histiotrophic
      nutrition involving pinocytosis of materials from uterine gland secretions,
      lysosomal degradation, and transfer of the products to the embryo. Interference
      with histiotrophic trafficking through the invYSP by high-molecular-weight
      molecules (such as trypan blue) causes malformations and resorptions. Later in
      gestation, rodents form a definitive chorioallantoic placenta (CAP). By contrast,
      humans and dogs never develop an invYSP, relying exclusively on the CAP. Given
      their large size (approximately 250 kD), hemoglobin-based oxygen carriers (HBOC),
      being developed as blood substitutes, could be expected to interfere with
      histiotrophic trafficking through the invYSP. During initial toxicity testing,
      intravenous infusions of HBOC caused pronounced developmental toxicity in rats
      exposed during the pre-CAP period. Assuming that HBOC interfered with invYSP
      function, we hypothesized that these findings would not apply to humans or dogs,
      which lack an invYSP. Subsequent extensive developmental toxicity studies in dogs
      produced no developmental toxicity after intravenous infusion at the maximum
      tolerated dose. In view of the existing species-specific placental differences
      and HBOC's demonstrated, exclusive interference with invYSP histiotrophic
      nutrition, HBOC is not expected to cause abnormal development in humans or other
      mammals that do not develop an invYSP.

PMID- 16417040
TI  - Mode of action: inhibition of histone deacetylase, altering WNT-dependent gene
      expression, and regulation of beta-catenin--developmental effects of valproic
      acid.
AB  - Valproic acid (VPA) has long been known to cause spina bifida, a neural tube
      defect, and other effects in fetuses of women treated with this drug.
      Toxicological tests in laboratory mice and rats at human therapeutic doses also
      show neural tube and other defects. Studies show that VPA alters Wnt signaling in
      human and animal cells, inducing Wnt-dependent gene expression at doses that
      cause developmental effects. Structural analogues of VPA that do not have this
      effect on Wnt signaling do not cause developmental effects. Similarly,
      Trichostatin A, a compound that mimics VPA in its effects on Wnt gene expression,
      also causes similar developmental effects. Alteration of Wnt signaling is
      empirically well supported as the postulated mode of action (MOA) for VPA's
      developmental effects in animals. VPA causes alteration of Wnt signaling in both
      human and animal cells systems at the same dose levels. The correspondence of
      effects on signaling and of effects on development in animals and humans supports
      the view that alteration of Wnt signaling is a relevant MOA in humans.

PMID- 16417042
TI  - Mode of action: angiotensin-converting enzyme inhibition--developmental effects
      associated with exposure to ACE inhibitors.
AB  - Relative to species tested in laboratory studies, the human fetus displays higher
      vulnerability to enalapril and other angiotensin-converting enzyme inhibitors
      (ACEI) exhibiting a malformative syndrome that does not appear to have a similar
      counterpart in experimental animals. An important reason for this higher
      vulnerability is the earlier intrauterine development of the kidney and the renin
      angiotensin-aldosterone (RAS) system in humans, organ systems that are specific
      targets of ACEI's pharmacological effect. In humans, these systems begin
      developing prior to the onset of skeletal ossification at the end of the first
      trimester, with continuing vulnerability throughout the pregnancy. In most animal
      species tested, these target systems develop close to term, when the fetus is
      relatively more mature and less vulnerable to the effects of developmental
      toxicants. For this reason, animal studies that follow standard protocols and
      evaluate developmental toxicity only for exposures during embryogenesis will miss
      developmental effects arising secondary to disruption of target systems that
      develop after the period of major organogenesis. Thus, although the animal mode
      of action (MOA) for enalapril and other ACEI is plausible in humans, differences
      in the timing of development of critical target organ systems, particularly the
      renal system and RAS, explain the absence of definitive structural abnormalities
      in test animals.

PMID- 16417043
TI  - Mode of action: neurotoxicity induced by thyroid hormone disruption during
      development--hearing loss resulting from exposure to PHAHs.
AB  - An increasing incorporation of mode of action (MOA) information into risk
      assessments has led to examination of animal MOAs to determine relevance to
      humans. We examined a specific MOA for developmental neurotoxicity using the
      MOA/Human Relevance Framework (Meek et al., 2003). The postulated MOA of
      ototoxicity in rats involves early postnatal exposure to polychlorinated
      biphenyls (PCBs) via lactation, an upregulation of hepatic uridine
      diphosphoglucuronyltransferases (UGTs), and subsequent hypothyroxinemia during a
      critical period of cochlear development, with the ultimate neurotoxic consequence
      of hearing loss. This review concludes with high confidence in the animal MOA and
      medium confidence for the interspecies concordance for the key events in the MOA.
      Possible interspecies differences in toxicodynamic factors moderate confidence in
      some key events. In addition, there is a question of whether ambient human
      exposures are large enough to cause human fetal hypothyroxinemia to the degree
      needed to cause hearing loss. Data gaps identified by this analysis include a
      need to characterize the induciblity of human fetal UGTs and the comparative
      sensitivity of UGT induction by xenobiotics in rats and humans. Research on these
      areas of uncertainty will increase confidence that this MOA for PCBs is not
      likely to not occur in humans, assuming normal conditions of limited ambient
      exposure.

PMID- 16417044
TI  - Mode of action: developmental thyroid hormone insufficiency--neurological
      abnormalities resulting from exposure to propylthiouracil.
AB  - Because thyroid hormone is essential for normal brain development before and
      after birth, environmental chemicals that interfere with thyroid hormone
      signaling can adversely affect brain development. Adverse consequences of thyroid
      hormone insufficiency depend both on severity and developmental timing,
      indicating that environmental antithyroid factors may produce different effects
      at different developmental windows of exposure. Mechanistic studies can provide
      important insight into the potential impact of chemicals on human thyroid
      function, but relevance to humans must be systematically evaluated. This kind of
      analysis depends on data sets that include information about animals and humans.
      The drug 6-n-propyl-2-thiouracil (PTU) is used in animals to experimentally
      manipulate serum thyroid hormone levels, and in humans to treat patients,
      including pregnant women, with Graves' disease. A systematic analysis of the mode
      of action (MOA) of PTU in rats and in humans discloses similar modes of action.
      While the analysis predicts that PTU doses that produce thyroid hormone
      insufficiency in humans would adversely affect the developing brain, careful
      monitoring of PTU administration in pregnant and lactating humans keeps infant
      serum thyroid hormone levels within the normal range.

PMID- 16417045
TI  - Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects
      on human health.
AB  - Aldehydes are organic compounds that are widespread in nature. They can be formed
      endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate
      autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed
      metabolic activation. This review compares the reactivity of many aldehydes
      towards biomolecules particularly macromolecules. Furthermore, it includes not
      only aldehydes of environmental or occupational concerns but also dietary
      aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs
      that are aldehydes or form reactive aldehyde metabolites that cause side-effect
      toxicity are also included. The effects of these aldehydes on biological
      function, their contribution to human diseases, and the role of nucleic acid and
      protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms,
      respectively, as well as carbonyl signal transduction and gene expression, are
      reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes
      are also reviewed, as well as the toxicological and anticancer therapeutic
      effects of metabolizing enzyme inhibitors. The human health risks from clinical
      and animal research studies are reviewed, including aldehydes as haptens in
      allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic
      drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and
      the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity,
      diabetes/hypertension, sclerosing peritonitis, cerebral
      ischemia/neurodegenerative diseases, and other aging-associated diseases.

PMID- 16417047
TI  - Common sense for a common problem: the question of screening the average-risk
      population for colorectal neoplasia.

PMID- 16417048
TI  - Polling surgeons.

PMID- 16417049
TI  - Colorectal cancer screening: practices and attitudes of gastroenterologists,
      internists and surgeons.
AB  - BACKGROUND: The Canadian Task Force on Preventive Health Care has recommended the
      use of annual or biennial fecal occult blood testing (FOBT) and flexible
      sigmoidoscopy in the periodic health examination of asymptomatic people over 50
      years of age. Therefore, we decided to ascertain the current colorectal cancer
      (CRC) screening practices and attitudes of surgeons, gastroenterologists and
      internists. METHODS: In June 2002 (with a final mailing in December 2002), a
      questionnaire was sent to all gastroenterologists, internists and surgeons in
      Alberta. It included items on demographic and practice characteristics, CRC
      screening practices and opinions about CRC screening. RESULTS: Responses were
      received from 42 gastroenterologists, 83 internists and 68 surgeons. Overall, 141
      of 187 respondents (75.4%, 95% confidence interval [CI] 68.6%-81.4%) recommended
      that average-risk adults undergo CRC screening. Internists were less likely to
      recommend screening than either gastroenterologists or surgeons (95% CI for the
      difference 7.2%-32.8%). The most commonly recommended screening test was
      colonoscopy (70%), followed by FOBT (65%), flexible sigmoidoscopy (47%) and air
      contrast barium enema (31%). Colonoscopy was the only test recommended by 7
      (22.6%) of 33 gastroenterologists, 9 (16.4%) of 59 surgeons and 3 (6.1%) of 49
      internists. Respondents were more likely to list barriers to the use of
      colonoscopy (mean 5 barriers) for screening than for either FOBT or flexible
      sigmoidoscopy (mean 2 barriers for both tests). Only 3 respondents indicated that
      they themselves would not undergo screening. Colonoscopy was the only screening
      test that 135 (70.0%) of the 193 would themselves undergo. CONCLUSIONS: The
      majority of Alberta specialists recommend CRC screening for average-risk adults.
      Colonoscopy was the most commonly recommended test, despite the perception of
      more barriers to that technique and the 2001 guidelines prepared by the Canadian
      Task Force for Preventive Health Care, which did not support colonoscopy.

PMID- 16417050
TI  - Development of quality indicators for colorectal cancer surgery, using a 3-step
      modified Delphi approach.
AB  - BACKGROUND: Little performance measurement has been undertaken in the area of
      oncology, particularly for surgery, which is a pivotal event in the continuum of
      cancer care. This work was conducted to develop indicators of quality for
      colorectal cancer surgery, using a 3-step modified Delphi approach. METHODS: A
      multidisciplinary panel, comprising surgical and methodological co-chairs, 9
      surgeons, a medical oncologist, a radiation oncologist, a nurse and a
      pathologist, reviewed potential indicators extracted from the medical literature
      through 2 consecutive rounds of rating followed by consensus discussion. The
      panel then prioritized the indicators selected in the previous 2 rounds. RESULTS:
      Of 45 possible indicators that emerged from 30 selected articles, 15 were
      prioritized by the panel as benchmarks for assessing the quality of surgical
      care. The 15 indicators represent 3 levels of measurement (provincial/regional,
      hospital, individual provider) across several phases of care (diagnosis, surgery,
      adjuvant therapy, pathology and follow-up), as well as broad measures of access
      and outcome. The indicators selected by the panel were more often supported by
      evidence than those that were discarded. CONCLUSIONS: This project represents a
      unique initiative, and the results may be applicable to colorectal cancer surgery
      in any jurisdiction.

PMID- 16417051
TI  - Prospective evaluation of hand-held focused abdominal sonography for trauma
      (FAST) in blunt abdominal trauma.
AB  - BACKGROUND: Ultrasonography (US) has become indispensable in assessing the status
      of the injured patient. Although hand-held US equipment is now commercially
      available and may expand the availability and speed of US in assessing the trauma
      patient, it has not been subjected to controlled evaluation in early trauma care.
      METHODS: A 2.4-kg hand-held (HH) US device was used to perform focused abdominal
      sonography for trauma (FAST) on blunt trauma victims at 2 centres. Results were
      compared with the "truth" as determined through formal FAST examinations (FFAST),
      CT, operative findings and serial examination. The ability of HHFAST to detect
      free fluid, intra-abdominal injuries and injuries requiring therapeutic
      interventions was assessed. RESULTS: HHFAST was positive in 80% of 313 patients
      who needed surgery or angiography. HHFAST test performances (sensitivity,
      specificity, positive and negative predictive values, likelihood ratios of
      positive and negative test results) were 77%, 99%, 96%, 94%, 95%, 95 and 0.2,
      respectively, for free fluid, and 64%, 99%, 96%, 89%, 90%, 74 and 0.4,
      respectively, for documented injuries. HHFAST missed or gave an indeterminate
      result in 8 (3%) of 270 patients with injuries who required therapeutic
      intervention and 25 (9%) of 270 patients who did not require intervention. FFAST
      performance was comparable. CONCLUSIONS: HHFAST performed by clinicians detects
      intraperitoneal fluid with a high degree of accuracy. All FAST examinations are
      valuable tests when positive. They will miss some injuries, but the majority of
      the injuries missed do not require therapy. HHFAST provides an early extension of
      the physical examination but should be complemented by the selective use of CT,
      rather than formal repeat US.

PMID- 16417052
TI  - Intra-articular steroid hip injection for osteoarthritis: a survey of orthopedic
      surgeons in Ontario.
AB  - BACKGROUND: Intra-articular steroid hip injection (IASHI) has been prescribed for
      painful hip arthritis since the 1950s, but with advances in medical and surgical
      management its role is less certain today. There are very few published data on
      the utility or prescribing patterns of IASHI. METHODS: We developed a
      questionnaire to seek expert opinion on IASHI that we distributed to practising
      Ontario-based members of the Canadian Orthopaedic Association. We systematically
      describe the current practices and expert opinion of 99 hip surgeons (73%
      response rate), focusing on indications, current use and complications
      experienced with IASHI. RESULTS: Only 56% of surgeons felt that IASHI was
      therapeutically useful, with 72% of surgeons estimating that 60% or less of their
      patients achieved even transient benefit from IASHI. One-quarter of the surgeons
      believe that IASHI accelerates arthritis progression, most of whom had stated
      that it would be no great loss if IASHI was no longer available. Nineteen percent
      of the surgeons believed that the infection rate related to total hip
      arthroplasty (THA) may be increased after IASHI, and this was associated with
      fewer IASHIs ordered per year, compared with the number prescribed by those who
      did not feel that infection rates would increase. CONCLUSIONS: This systematic
      collection of expert opinions demonstrates that substantial numbers of surgeons
      felt that, in their patients, IASHI was not therapeutically helpful, may
      accelerate arthritis progression or may cause increased infectious complications
      after subsequent THA.

PMID- 16417053
TI  - A mathematical model for fresh frozen plasma transfusion strategies during major
      trauma resuscitation with ongoing hemorrhage.
AB  - BACKGROUND: Randomized controlled trials of how best to administer fresh frozen
      plasma (FFP) in the presence of ongoing severe traumatic hemorrhage are difficult
      to execute and have not been published. Meanwhile, coagulopathy remains a common
      occurrence during major trauma resuscitation and hemorrhage remains a major cause
      of traumatic deaths, suggesting that current coagulation factor replacement
      practices may be inadequate. METHODS: We used a pharmacokinetic model to simulate
      the dilutional component of coagulopathy during hemorrhage and compared different
      FFP transfusion strategies for the prevention or correction, or both, of
      dilutional coagulopathy. Assuming the rates of volume replacement and loss are
      roughly equal, we derived the hematocrit and plasma coagulation factor
      concentration over time based on the rate of blood loss and replacement, the
      hematocrit and coagulation factor concentration of the transfusate, and the
      hematocrit and plasma factor concentration at the time when FFP transfusion
      begins. RESULTS: Once excessive deficiency of factors has developed and bleeding
      is unabated, 1-1.5 units of FFP must be given for every unit of packed red blood
      cells (PRBC) transfused. If FFP transfusion should start before plasma factor
      concentration drops below 50% of normal, an FFP:PRBC transfusion ratio of 1:1
      would prevent further dilution. CONCLUSION: During resuscitation of a patient who
      has undergone major trauma, the equivalent of whole-blood transfusion is required
      to correct or prevent dilutional coagulopathy.

PMID- 16417054
TI  - Review of a Canadian forum on international surgery: the Bethune Round Table.
AB  - The Bethune Round Table is an annual conference on international surgery that is
      unique in North America. Hosted by the Office of International Surgery at the
      University of Toronto, the conference provides a forum for profiling the global
      realities of surgical need, particularly as they relate to vulnerable and
      disadvantaged people of low-income countries. The 2004 Bethune Round Table,
      drawing on input from 4 continents, highlighted "emerging directions".
      Presentations and discussions focused on the themes of current surgical
      realities, the implications for surgical education, the role of specialized
      surgical services and the function of surgical partnerships.

PMID- 16417055
TI  - Radiology for the surgeon. Musculoskeletal case 36. Primary leiomyosarcoma of the
      tibia.

PMID- 16417056
TI  - Posterolateral approach for open reduction and internal fixation of trimalleolar
      ankle fractures.

PMID- 16417057
TI  - Canadian Association of General Surgeons and American College of Surgeons
      evidence based reviews in surgery. 15. Biphasic CT with mesenteric CT angiography
      in the evaluation of acute mesenteric ischemia: initial experience.

PMID- 16417058
TI  - Total knee arthroplasty in Klippel-Trenaunay syndrome.

PMID- 16417060
TI  - NIDA campaign to raise awareness of drug abuse--HIV connection.

PMID- 16417059
TI  - Soft-tissue textiloma: a potential diagnostic pitfall.

PMID- 16417061
TI  - Government-controlled health care is not the solution.

PMID- 16417062
TI  - Making psychotherapy work in primary care medicine.

PMID- 16417063
TI  - The 2006 Childhood and Adolescent Immunization Schedule: reflections at the 50th
      anniversary of the polio vaccine.

PMID- 16417064
TI  - IVF therapy for unexplained infertility.

PMID- 16417065
TI  - Is oral vitamin B12 as effective as intramuscular injection?

PMID- 16417066
TI  - Anticholinergic drugs for overactive bladder.

PMID- 16417067
TI  - Medications for migraine prophylaxis.
AB  - Sufficient evidence and consensus exist to recommend propranolol, timolol,
      amitriptyline, divalproex, sodium valproate, and topiramate as first-line agents
      for migraine prevention. There is fair evidence of effectiveness with gabapentin
      and naproxen sodium. Botulinum toxin also has demonstrated fair effectiveness,
      but further studies are needed to define its role in migraine prevention. Limited
      evidence is available to support the use of candesartan, lisinopril, atenolol,
      metoprolol, nadolol, fluoxetine, magnesium, vitamin B2 (riboflavin), coenzyme
      Q10, and hormone therapy in migraine prevention. Data and expert opinion are
      mixed regarding some agents, such as verapamil and feverfew; these can be
      considered in migraine prevention when other medications cannot be used. Evidence
      supports the use of timed-release dihydroergotamine mesylate, but patients should
      be monitored closely for adverse effects.

PMID- 16417068
TI  - Information from your family doctor. Medicines to prevent migraine headaches.

PMID- 16417069
TI  - Cognitive therapy for depression.
AB  - Cognitive therapy is a treatment process that enables patients to correct false
      self-beliefs that can lead to negative moods and behaviors. The fundamental
      assumption is that a thought precedes a mood; therefore, learning to substitute
      healthy thoughts for negative thoughts will improve a person's mood, self
      concept, behavior, and physical state. Studies have shown that cognitive therapy
      is an effective treatment for depression and is comparable in effectiveness to
      antidepressants and interpersonal or psychodynamic therapy. The combination of
      cognitive therapy and antidepressants has been shown to effectively manage severe
      or chronic depression. Cognitive therapy also has proved beneficial in treating
      patients who have only a partial response to adequate antidepressant therapy.
      Good evidence has shown that cognitive therapy reduces relapse rates in patients
      with depression, and some evidence has shown that cognitive therapy is effective
      for adolescents with depression.

PMID- 16417070
TI  - Information from your family doctor. Cognitive therapy for depression: what you
      should know.

PMID- 16417071
TI  - Cerebral palsy: an overview.
AB  - The presentation of cerebral palsy can be global mental and physical dysfunction
      or isolated disturbances in gait, cognition, growth, or sensation. It is the most
      common childhood physical disability and affects 2 to 2.5 children per 1,000 born
      in the United States. The differential diagnosis of cerebral palsy includes
      metabolic and genetic disorders. The goals of treatment are to improve
      functionality and capabilities toward independence. Multispecialty treatment
      teams should be developed around the needs of each patient to provide
      continuously updated global treatment care plans. Complications of cerebral palsy
      include spasticity and contractures; feeding difficulties; drooling;
      communication difficulties; osteopenia; osteoporosis; fractures; pain; and
      functional gastrointestinal abnormalities contributing to bowel obstruction,
      vomiting, and constipation. Valid and reliable assessment tools to establish
      baseline functions and monitor developmental gains have contributed to an
      increasing body of evidenced-based recommendations for cerebral palsy. Many of
      the historical treatments for this ailment are being challenged, and several new
      treatment modalities are available. Adult morbidity and mortality from ischemic
      heart disease, cerebrovascular disease, cancer, and trauma are higher in patients
      with cerebral palsy than in the general population.

PMID- 16417072
TI  - Information from your family doctor. Cerebral palsy in children: what you should
      know.

PMID- 16417073
TI  - Management of histologic abnormalities of the cervix.
AB  - The American Society for Colposcopy and Cervical Pathology sponsored a consensus
      conference in 2001 to develop evidence-based guidelines for women with histologic
      abnormalities of the cervix. The options for management of cervical
      intraepithelial neoplasia 1, 2, and 3 are ranked according to the strength of the
      recommendation and the quality of the evidence. Follow-up with repeat cytology at
      six and 12 months or DNA testing for high-risk types of human papillomavirus at
      12 months is the preferred management approach for women with cervical
      intraepithelial neoplasia 1 and satisfactory initial colposcopy. If results from
      repeat cytology are reported as atypical squamous cells of undetermined
      significance or greater, or if DNA human papillomavirus testing is positive for
      oncogenic types of the virus, repeat colposcopy is preferred. When the initial
      colposcopy is unsatisfactory, a diagnostic excisional procedure is preferred.
      Follow-up without treatment is acceptable only in women who are pregnant and
      adolescents with cervical intraepithelial neoplasia 1 who had unsatisfactory
      colposcopy. Biopsy-confirmed cervical intraepithelial neoplasia 2 and 3 requires
      treatment except during pregnancy and in compliant adolescents with cervical
      intraepithelial neoplasia 2 and negative endocervical curettage. When colposcopy
      is satisfactory, treatment includes ablative or excisional procedures. A
      diagnostic excisional procedure is recommended in women with biopsy-confirmed
      cervical intraepithelial neoplasia 2 or 3 and unsatisfactory colposcopy.

PMID- 16417074
TI  - Screening and interventions for overweight in children and adolescents:
      recommendation statement.

PMID- 16417075
TI  - Urine dipstick for diagnosing urinary tract infection.

PMID- 16417076
TI  - Itchy and painful ulceration on the penis.

PMID- 16417077
TI  - Physicians who do not follow screening guidelines.

PMID- 16417078
TI  - [PvuII genetic polymorphism of estrogen receptor alpha in the group of
      postmenopausal women with osteopenia and osteoporosis].
AB  - DESIGN: It was suggested that genetic factors play an important role in the
      regulation of bone mineral density and in the pathogenesis of bone fracture in
      osteoporosis. PvuII restriction polymorphism in the intron 1 of the gene coding
      estrogen receptor alpha (ER-alpha) is indicated to play a significant role in
      osteopenia and osteoporosis development. The goal of our study was to determine
      the frequency and the significance of PvuII polymorphism of the ER-alpha gene in
      the group of postmenopausal women with osteopenia and osteoporosis. MATERIALS AND
      METHODS: 93 postmenopausal women with osteopenia and osteoporosis (t-score lower
      than (-1), and 141 healthy postmenopausal women have been investigated for PvuII
      polymorphism of the ER-a gene using polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) assays. RESULTS: We have observed
      higher frequency of homozygous genotype PP (25.8 vs. 19.8%) and P allele (50.6
      vs. 46.1%) in the group of women with low level of t-score. In the osteopenic
      women (-2.5 < T-score < -1.0) the significant difference in the distribution of t
      score index and genotypes has been found. t-score index correlated with body mass
      index (BMI), mean body weight, BMD aged matched (AM) and BMD young adults (YA)
      index. The AM and YA index correlated with the number of pregnancies.
      CONCLUSIONS: The presence of PP genotype and P allele could be connected with
      higher bone loss and with the development of osteopenia and osteoporosis in
      postmenopausal women.

PMID- 16417079
TI  - [The effect of estrogen deficiency, estrogen and estro-progestagene therapy on
      total plasma homocysteine and serum lipid peroxide levels in postmenopausal
      women].
AB  - OBJECTIVES: Elevated plasma homocysteine (Hcy) concentration is a risk factor for
      atherosclerosis and venous thrombosis. DESIGN: an observational study. MATERIALS
      AND METHODS: 120 healthy women were recruited and divided in two subgroups-
      postmenopausal women (M-80 women) and premenopausal women (40 women) with normal
      menstruation as control group. 26 women with surgical menopause were treated with
      percutaneous estrogen therapy and remaining 54 women were treated with estro
      progestagen replacement therapy. Measurements of FSH and estradiol was made using
      radioimmunoassay. HCY was assessed using enzymatic conversion method. RESULTS:
      Concentrations of Hcy and lipid peroxides (LPO) in postmenopausal study group
      were higher than in the premenopausal. Treatment with estradiol (E2) alone or in
      combination with medroxyprogesterone acetate decreased LPO and Hcy concentrations
      to levels observed in premenopausal group. CONCLUSIONS: Our results suggest that
      estrogens have a profound influence on Hcy and LPO levels. Reduction in Hcy
      levels after treatment lowers the production of free radicals and thus
      contributes to lipid peroxidation decrease and LPO levels reduction after
      therapy. A practical conclusion may be proposed: in postmenopausal women with
      elevated Hcy levels who require hormonal replacement therapy, Hcy level control
      is indicated in order to administer such a therapy, which decreases Hcy
      concentrations.

PMID- 16417080
TI  - [Estimated results of prophylactic physical examinations detecting cervical
      cancer in Center of Oncology in Bydgoszcz in years 2001-2003].
AB  - OBJECTIVES: Kujawsko-pomorskie province is a region with high morbidity and death
      rate from uterine cervix cancer. One of the methods of improve this situation is
      to perform prophylactic physical examinations to find the least advanced stages
      as possible. DESIGN: The aim of the study was to estimate the results of
      prophylactic physical examinations for cervical cancer that took place in Center
      of Oncology in Bydgoszcz between 2001-2003. MATERIALS AND METHODS: Pap Smear with
      prophylactic examination for breast cancer were taken in 3 medical centers. First
      on, according to called "mobile", was localized in the health service center,
      second one in the bus with the mammography, reaching distant areas and third one
      was performing examinations locally. Cytologic examinations were rated Bethesda
      system and according to Papanicolau. There were 28372 women examined (age 30-60).
      8996 medical examinations were performed by "mobile" device, 6726 in the second
      center and 12650 locally. 8237 examinations were performed in 2001 year, 9444 in
      2002, and 10691 in 2003. RESULTS: Among all the Pap Smears the results were as
      following: I group--14267, II group--14017, III group--73, IV group--13, V group-
      2.43 (0.15%)intraepithelial dysplasia was found in them CIN I--23 (0.08%), CIN II
      -10 (0.035%), CIN III--10 (0.35%).21 (0.1%) cervical cancers were detected, 12 of
      them were praeinvasive cancers. 0.31% of the all Pap Smears were abnormal.
      CONCLUSIONS: (1) The number of abnormal Pap Smears and severe dysplastic lesions
      proves the usefulness of the prophylactic physical examinations. (2) The above
      programme shows the that the access to oncological care for women living in rural
      areas, has a social aspect and should have affect the health awareness of the
      potential patients.

PMID- 16417081
TI  - [Factors influencing total fertility rate (TFR) in Africa].
AB  - AIM: The aim of the study was to estimate how the cultural and religious factors
      contribute to high total fertility rate in Africa and to denying the use of
      contraceptives. MATERIAL AND METHOD: A group of 100 women, mainly from rural
      areas, was interviewed in Southern Africa during the period of 1996-2002.
      Questions concerned motivation to high total fertility rate (average number of
      lifetime births per woman in particular country or population) and low rate of
      contraception use. RESULTS AND CONCLUSIONS: The main motivating factors to high
      TFR were cultural and religious beliefs, like the value of children as carriers
      of traditions, religion, genetics and also the emphasis on Old Testament in
      African Christianity. In 92 cases husbands played dominant role in deciding about
      the size of the family and denying the use of free contraceptives by women.

PMID- 16417082
TI  - [Usefulness assessment of selected proinflammatory cytokines' level in cervico
      vaginal fluid of pregnant women as an early marker of preterm delivery].
AB  - OBJECTIVES: Recent studies have suggested that proinflammatory cytokines might
      play a crucial role in the mechanism of preterm labour and delivery. The main aim
      of this prospective study was to evaluate the usefulness of selected
      proinflammatory cytokines' (IL-1 alpha, IL-1 beta, IL-6 and IL-8) levels in
      cervico-vaginal fluid of pregnant women as an early marker of preterm delivery.
      MATERIAL AND METHODS: Cervico-vaginal fluids were obtained from 107 pregnant
      women at 22 to 34 weeks' gestation, including 61 women with threatened preterm
      labour (TPL) and 46 women with physiological course of pregnancy (reference
      group). Those samples were analyzed for the concentrations of selected cytokines
      using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital
      tract microbiology was diagnosed using Gram stain method according to Spiegel's
      criteria and by culture. RESULTS: Mean gestational age at the time of sampling
      was 28.6 weeks. Mean time between sampling and delivery was 8,24 weeks in TPL
      group and 10.2 weeks in reference group. BV was diagnosed in 25.2% of subjects
      under study. M. hominis and U. urealyticum were diagnosed more frequently among
      women from TPL group (25.9% vs 14.9% and 36.2% vs 17.0%, respectively). Out of
      107 women 15 (14.0%) delivered before 37th week of gestation. The rate of
      preterem delivery was significantly higher in threatened preterm labour group-
      21.3% is comparison to reference group--4.3%. Median cervico-vaginal
      concentration of IL-1 alpha, IL-1 beta, IL-6 and IL-8 did not differ between
      preterm and term delivery group. Only women with lower genital tract infection
      and one cytokine's low concentration (below 25th percentile) presented a higher
      risk of preterm delivery--OR=2,91. If IL-1 alpha and IL-1 beta concentrations
      were below 25th percentile, the calculated risk of preterm delivery was OR =
      4.65. The highest risk was noted for women with lower genital tract infection and
      low cervico-vaginal concentrations of IL-1 alpha and IL-8--OR = 8.0 (3.20-20.01).
      CONCLUSIONS: The early gestation cytokines' levels in cervico-vaginal fluid of
      pregnant women could be useful for prediction of preterm delivery only among
      women with lower genital tract infection.

PMID- 16417083
TI  - [Relationship between doppler velocimetry at middle cerebral artery and umbilical
      artery and status of newborn after delivery].
AB  - OBJECTIVES: Aim of research was estimation of correlation between doppler
      parameters and fetal state after delivery. MATERIAL AND METHODS: One hundred
      fifty-one pregnancies treated in Dept. of Obstetrics and Gynecology of Medical
      Academy in Bydgoszcz was investigated between 1998-2002. Pregnancies were
      estimated between 27 and 43 Hbd. Ultrasound examination using pulse and color
      Doppler was performed (ACUSON XP 128) and PI, RI, S/D, MCA, UA were estimated.
      DESIGN: Following doppler parameters were analyzed: pulsatile index (PI),
      resistance index (RI) and systolic/diastolic ratio (S/D) in middle cerebral
      artery (MCA) and in umbilical cord artery (UA). The newborn children were
      estimated by Apgar score in first minute of life (AP1). Correlation between
      amount of amniotic fluid index (AFI) and newborn state in first minute after
      delivery was investigated too. RESULTS: There were following correlations in this
      investigation: (1) negative between UA PI and AP1 (-0.26); (2) negative between
      UA RI and AP1 (-0.23); (3) negative between UAS/D and AP1 (-0.16); (4) negative
      between AFI and API (-0.06); (5) lack of statistical correlation between MCA PI,
      MCA RI, MCA S/D and AP1. We considered following covariancies: (1) negative
      between AFI and AP1 (-1.03); (2) negative between UA S/D and AP1 (-0.42); (3)
      negative between UA PI and AP1 (-0.23); (4) negative between UA RI and AP1 (
      0.09). CONCLUSIONS: We concluded that Doppler investigations by measure of
      parameters of blood flow in umbilical cord artery (PI, RI, S/D) can be predictive
      to fetal threat and useful in estimation of newborn state.

PMID- 16417084
TI  - [Mast cells as a source of nitric oxide in the human placenta--morphometric
      analysis in preeclampsia complicated pregnancy].
AB  - The aim of the study was to test hypothesis, that in placenta mast cells are
      significant source of iNOS. MATERIAL: Placentas were collected after term
      delivery from healthy (control, n=13) and preeclamptic (n=11) women. Mast cells
      and iNOS expression were detected in obtained samples with monoclonal anti-iNOS
      and anti-tryptase antibodies. Next, morphometric analysis were performed. There
      were no significant difference between iNOS expression and number of iNOS
      positive cells in normal and preeclamptic placentas. There was a significant
      increase in mast cells number in preeclamptic placentas (8.32 +/- 1.3 SD vs 5.14
      +/- 1.2 SD in control) and decrease in percentage of iNOS positive cells among
      them (68.1% vs 23.6%). We conclude, that in uncomplicated pregnancies, mast cells
      are the main source of iNOS in placenta while in preeclampsia they loss their
      potential to synthetase iNOS.

PMID- 16417085
TI  - [Mast cells, histamine and development of the placental vascular network in
      pregnancies complicated by preeclampsia and intrauterine growth retardation].
AB  - Importance of angiogenesis in proper development of placenta is unquestioned.
      Abnormalities in vascular development are typical for complications of pregnancy:
      intrauterine growth retardation (IUGR) and preeclampsia (PE). As mast cells are
      involved in new vessels sprouting and development we tried to disclose if they
      can be involved in etiology or pathogenesis of IUGR and/or PE. MATERIAL AND
      METHODS: Placentas from PE-complicated pregnancies (n=11), IUGR-complicated
      pregnancies (n=10), and from healthy women--controls (n=13) were obtained after
      cesarean sections. Histamine concentration was measured and immunohistochemical
      staining for mast cell tryptase was performed. Microscopic slides of placental
      tissue were analyzed with morphometric software. RESULTS: We disclosed increased
      histamine concentration in PE group--227.3 +/- 17.7 (in ng of histamine per 1 g
      of tissue) and decreased concentration in IUGR group 114.3 +/- 13.5 vs control-
      178.1+/- 18.9. Histamine concentration corresponded with density of mast cells in
      examined groups: PE group--8.32 cells/mm2 +/- 1.3, IUGR--3.07 +/- 1.05 and
      control--5.14 +/- 1.2. The mean area of mast cells identified in PE as well as in
      IUGR group was smaller than the mean area of mast cells in controls. V/EVT index
      was decreased in PE and IUGR group in comparison to controls, respectively: 0.15
      +/- 0.018; 0.12 +/- 0.014; 0.23 +/- 0.029. CONCLUSIONS: We suggest that
      differences in mast cells density and corresponding differences in histamine
      concentration are associated with pathogenesis of PE and IUGR or are consequence
      of primary cause.

PMID- 16417086
TI  - [Sister Mary Joseph's nodule disclosing an ovarian cancer].
AB  - A case report of the patient with umbilical tumor--metastasis and the first
      symptom of an ovarian carcinoma. Anatomical and embryological origin of umbilical
      metastases, clinical picture, diagnostic procedure and therapeutic management
      were presented.

PMID- 16417087
TI  - [Heterotopic pregnancy].
AB  - We report a case of combined intrauterine and extrauterine (tubal) pregnancy in
      24-year-old woman. The patient was admitted to the Clinic at 9 weeks gestational
      age with abdominal pain lasting 2 hours. Pelvic ultrasonography revealed alive 9
      week intrauterine pregnancy, free fluid in the peritoneal cavity and left adnexal
      mass. A left salpingectomy was performed, with removal of ruptured ampulla with
      ectopic pregnancy, without complications. The intrauterine pregnancy proceeded
      uneventfully to 39 weeks, was terminated by cesarean section, resulting in birth
      of a healthy female infant of 3630 grams.

PMID- 16417088
TI  - [Subsequent pregnancy (twin) in woman with autoimmunological hepatitis].
AB  - Autoimmunological hepatitis is a long lasting disease with periods of recurrences
      and remissions. There is a limited knowledge on this subject during the
      pregnancy. We present a case of a subsequent pregnancy (twin) in woman with
      autoimmunological hepatitis. The patient's condition between both pregnancies was
      so severe that she was assigned for organ transplantation. However after
      treatment with prednisolone and azathioprine patient's outcome improved. The
      patient got pregnant in a short time after remission. Pregnancy did not have any
      negative influence on symptoms of the disease in this case; moreover we observed
      complete remission of the disease.

PMID- 16417089
TI  - [Contemporary methods of treating age-related infertility].
AB  - Age-related infertility that is caused by diminished reproductive potential is
      both medical and social problem of a great concern. Changes in modern ways of
      life make women postpone the decision of starting up a family, what may reduce
      their chances of having a healthy baby. It is also a problem of subfertile
      couples who after many years of insufficient treating approach the period where
      the age imposes on primary causes of infertility, what even more reduces the
      chance of pregnancy. The main reason of this is increased number of chromosomal
      abnormalities resulting in lower quality of oocytes. There is a lot of research
      being held on the reconstruction of gametes by transferring the nucleus or
      cytoplasm among the oocytes derived from young and older patients. However, it
      has not brought the expected results so far. The method of preimplantation
      genetic diagnosis--aneuploidy screening (PGD-AS) in patients older than 35 gives
      some hope for improving the efficiency of infertility treatment. Nevertheless,
      oocyte donation still remains the most effective and applied method of assisted
      reproduction in the group of older patients.

PMID- 16417090
TI  - [Resuscitation of a pregnant woman].
AB  - Most pregnant women have little interest in thinking about the prospect of death.
      Mortality related to the pregnancy itself is rare, occurring in an estimated 1 of
      every 30 000 deliveries. Although cardiopulmonary arrest rarely occurs in
      pregnant women, it is important that the health care team knows the appropriate
      actions to take in such an event, to promote positive outcomes for both mother
      and fetus. We discuss important pathophysiological alterations during pregnancy
      and, including recommendations in the available literature, we present a
      standardized protocol for life support for mother. Perimortem cesarean section is
      rarely required, but it is important topic for two reasons. First, there is a
      clear imperative to promptly decide and act when PMCD is indicated. As in all
      emergency care, knowledge must precede the crisis rather than await it. Second,
      indications for PMCD have broadened considerably since 1980s, and the procedure
      may attain a more prominent role in the future. We believe that prompt cesarean
      delivery is the key to maternal and infant survival in such cases.

PMID- 16417091
TI  - [Cervical glandular intraepithelial neoplasia topography and the risk of
      conisation].
AB  - OBJECTIVES: The frequency of endocervical adenocarcinoma is increasing in
      comparison with squamous cell carcinoma and it presents a very difficult
      diagnostic and therapeutic problem. DESIGN: The aim of this study was: 1)
      Evaluation of topography of the cervical glandular intraepithelial neoplasia
      (CGIN) 2) An analysis of the Human Papillomavirus (HPV) infection rate in
      samples. MATERIALS AND METHODS: 360 amputated uterine cervix samples with
      histologically-proven diagnosis of cervical intraepithelial neoplasia (CIN-3)
      were evaluated. The coexistence of pre-invasive lesions in squamous epithelium
      and endocervical columnar cell were investigated. Moreover CGIN topography and
      retrospective histopathological analysis were determined. A polymerase chain
      reaction (PCR) was performed using commercially available PCR Human
      Papillomavirus Typing Set to detect HPV infection. RESULTS: Among 360 positive
      cervical intraepithelial glandular neoplasia samples (CIN-3) 71 (19.7%) showed
      coexisting glandular lesions (CGIN-1, 2, 3). The lesions in endocervical
      glandular cells of CIGN-type were distributed from the distance up to 14 mm from
      the surface of cervix. Most of them were located no deeper than 1 mm from the
      surface of canal epithelium. HPV DNA was found in more than 90 preneoplastic
      glandular proliferations. The frequency of oncogenic HPV-16 and 18 presence was
      higher than non-oncogenic HPV. CONCLUSIONS: 1. CIN-3 is associated in about 20%
      with cervical glandular intraepithelial neoplasia (CGIN). 2. Topography of CGIN
      is important in planning the management. 3. Most of CIGN are associated with HPV
      infection.

PMID- 16417092
TI  - [Is glycodelin an important marker of endometrial receptivity?].
AB  - OBJECTIVE: Glycodelin A (GdA) is viewed as a uterine endometrium receptivity
      marker. The expression of GdA in the endometrium is mirrored in uterine fluid and
      in the serum. Thanks to its immunosuppressive properties GdA might regulate
      mechanisms of fertilization, implantation and further development of the embryo.
      DESIGN: The authors assessed the GdA concentration during implantation window of
      nonconceptional cycles in women with impaired reproduction. MATERIAL AND METHODS:
      Fluid from uterine cavity, serum and endometrial samples were obtained from 116
      women, among them 43 have had 2 or more miscarriages, while 52 were infertile.
      Control constituted 21 fertile women. In uterine fluid and serum the GdA
      concentration was assessed with ELISA Bioserv Diagnostic kits, and progesterone
      with electrochemiluminescence. Endometria obtained during hysteroscopy were
      evaluated in terms of conformity with the cycle dating. RESULTS: Statistically
      lower (p < 0,0001) compared to control GdA concentration in uterine fluid was
      found in infertile women. The lowest GdA values were obtained in women with
      idiopathic infertility and infertile women with endometriosis. GdA level of women
      with 2 or more miscarriages was no statistically significant different compared
      to control. The lowest concentration of GdA in this group of patients was found
      in women with luteal phase deficiency. The GdA concentration in the serum was
      three times lower compared to values noted in uterine fluid, and there was no
      difference between studied groups. CONCLUSION: Based on our research we might
      conclude that GdA has a more important role during implantation than in further
      development of the embryo.

PMID- 16417093
TI  - [Clinical analysis of patients with recurrences of borderline ovarian tumors
      including surgical treatment].
AB  - OBJECTIVES: Risk of recurrences of borderline ovarian tumors is low (7-10%) but
      the cases with incidence of recurrence have worse prognosis. The time between
      primary operation and the first diagnosis of recurrence and treatment is
      different. DESIGN: The purpose of the current study was to evaluate frequency and
      the methods of treatment patients with recurrences of borderline ovarian tumors.
      MATERIALS AND METHODS: The analyzing group consists of 129 patients with
      borderline tumors of the ovary (BTO) diagnosed and treated in Department of
      Gynecology between years 1978-2000. RESULTS: In our recurrences developed in 7%
      of patients. The recurrences in BTO were connected with stage of BTO, types of
      primary operations and residual disease. Recurrences developed in 5,9% patients
      with stage I and in 18,1% patients with stage II/III. Similarly recurrences
      developed in 5,8% patients with no residual disease and in 20% patient with
      residual disease. A higher relapse rate was observed in patients treated
      conservatively but recurrences was quickly recognized and efficaciously treated.
      5 years survival of patients without recurrences was 91,7% and with recurrences
      was 72,9%. CONCLUSIONS: 1. Risk of recurrences of BTO is low (7%) and depends on
      stage and residual disease. 2. Risk of recurrences is higher after primary
      conservative operation but long follow-up and regular gynecological examinations
      allows to early diagnosis and treatment of recurrences. 3. Prognosis of patients
      with recurrences of BTO is good. 5-years survival was 90,6% of group without and
      72,9% of group with recurrences of BTO.

PMID- 16417094
TI  - [Are the hormonal status or psychosocial conditions the major cause of female
      depressive disorders after menopause?].
AB  - The study was aimed to assess if the prevalence of female depressive disorders
      after menopause depends on their hormonal status (E2, FSH, testosterone, DHEAS)
      or psychosocial conditions, Moreover, the influence of HRT on female mood
      disorders was estimated. One hundred women (44=65 ys old) were included into the
      study. Ali patients were complaining of hot flushes for at least 6 months. Among
      these women 31% had depressive disorders at baseline. The hormonal status,
      psychosocial conditions and mood disorders (Beck's and Haniilton's scales) were
      assessed at the baseline and after 12 months in 50 women on HRT and in 20 control
      patients. After 1 year the depressive mood disappeared in 59% and worsened in
      5,9% of women taking HRT, whereas in the control group 35% of patient experienced
      depression. Among women on HRT the significant increase of serum DHEAS was
      observed in patients with improvement of mood as well as in depressed ones. Serum
      testosterone, 17P-estradiol and FSH levels did not differ between both groups.
      The higher scores of Beck's and Hamilton's scales were not associated with
      hormonal status but correlated with worsening of psychosocial conditions. The
      female depressive disorders after menopause are associated with their
      psychosocial conditions but not with their hormonal status.

PMID- 16417095
TI  - [Pregnancy outcome in five women after autologous bone marrow transplantation for
      acute lymphoblastic leukaemia].
AB  - There are reports of successful pregnancies in women with haematological
      malignancies after either autologous or allogeneic bone marrow transplantation
      (BMT). We report six cases of uncomplicated pregnancies in five women treated
      with high-dose chemotherapy, radiotherapy and autologous bone marrow
      transplantation (ABMT) for acute lymphoblastic leukaemia. One patient was
      diagnosed as having leukaemia during pregnancy. The pregnancy ended with medical
      termination. Each woman received conditioning regimens without total body
      irradiation (TBI). Of five women, who received AMBT, all resumed spontaneous
      cyclical menstruation post transplantation. All of them conceived naturally
      between 15-52 months following ABMT. We noted one miscarriage in our 29-year-old
      patient. Six pregnancies went to term and each resulted in the successful
      delivery of a full-term baby. We did not notice any case of relapse of leukaemia
      in pregnancy.

PMID- 16417096
TI  - [Epidural analgesia and the course of delivery in term primiparas].
AB  - OBJECTIVES: Epidural analgesia provides the most effective pain control during
      labor. Of great concern is its influence on the course of delivery and perinatal
      complications. DESIGN: The aim of the study was to assess the effect of epidural
      analgesia on the course of delivery and perinatal outcome. MATERIALS AND METHODS:
      609 deliveries among 1334 (323 women with epidural analgesia (53%) and 548
      without epidural analgesia (47%)) met the following criteria: primipara,
      singleton, live pregnancy, > =37 weeks' gestation, cephalic presentation of a
      fetus, lack of contraindication for vaginal delivery. The incidence of
      instrumental deliveries and fetal distress, duration of the first, second and
      third stage of labor, perinatal outcome, perinatal complications and perinatal
      blood loss and were analyzed. RESULTS: The incidence of fetal distress during
      second stage of labor was significantly higher in the epidural group (12.69 vs.
      6.99%, P=0.02). The incidence of fetal distress during first stage of labor did
      not differ in both groups (10.53% vs. 8.74%, NS). Cesarean sections rate was
      similar in epidural and non-epidural group (17.7 vs. 18.2%, NS). Among vaginal
      deliveries duration of the first and second stage of labor was longer in epidural
      group (6.5+/-2.4 vs. 5.4+/-2.5 godz., P=0,000003 and 47.3+/-34.8 vs. 29.1+/-25.8
      min., P=0.000003) and this was independent of period of time between onset of
      first stage of labor and epidural analgesia. Oxitocin use was significantly more
      frequent in the epidural group (20.6 vs. 10.3%, P<0.004). There were no
      statistically significant differences in the rates of instrumental vaginal
      deliveries, 1 and 5-minute Apgar scores, length of third stage of labor and
      perinatal blood loss in patients with and without epidural analgesia. Perinatal
      outcome did not depend on previous use of epidural analgesia or mode of analgesia
      for the operation in cesarean section subgroup. CONCLUSION: Epidural labor
      analgesia is associated with slower progress of labor but has no adverse effect
      on perinatal outcome and perinatal complications.

PMID- 16417097
TI  - [Can we expect decreasing the incidence of patent ductus arteriosus (PDA) in the
      population of premature neonates who had received antenatal steroid therapy?].
AB  - OBJECTIVES: The efficacy of antenatal steroid therapy (ANS--use with the
      recommendation from 1999; therapy repeated every 7-10 days; dexamethasone was
      used) on the incidence of RDS in neonates born before 34 weeks of gestation has
      been well documented in several studies. However, we know very little about the
      influence of ANS on patent ductus arteriosus (PDA). DESIGN: The purpose of this
      study was to assess the influence of ANS on the incidence of PDA in neonates born
      before 35 weeks of gestation. MATERIALS AND METHODS: The analysed population
      consisted of 425 newborns delivered at Research Institute Polish Mother's
      Memorial Hospital between 1996-1998. Patients were enrolled in three groups
      according to mode of ANS: Group I--complete ANS; Group II--partial ANS; Group III
      -without ANS (reference group, OR = 1). The complete ANS consisted of at least 24
      mg of dexamethasone with a first dose given not earlier then 24 hours before
      delivery. The analysis was based on retrospective evaluation of patient's medical
      records. PDA was diagnosed during echocardiographic examination or during
      autopsy. The incidence and risk of significant PDA in enrolled groups were
      estimated. RESULTS: Use of complete ANS has no influence of the incidence of PDA.
      In the partial ANS group the risk of PDA (OR 1,89; p = 0,052 vs group III) was
      increased. Risk of PDA was also higher in patients born before 29 weeks of
      gestation, especially from the partial ANS group. CONCLUSIONS: The antenatal
      steroid therapy has influence of the incidence of PDA. We observed higher risk of
      PDA in the group of neonates born before 29 weeks of gestation and in the partial
      ANS group.

PMID- 16417098
TI  - [Delayed positioning of multifilament tape (IVS transobturator tape) in treatment
      of stress urinary incontinence caused by the radiotherapy].
AB  - Radiotherapy is used to treat advanced stages of cervical cancer. Despite
      optimization of the doses delivered during radiotherapy chronic urinary tract
      complications still occur in 1-5% of patients. We report a case of 60 years old
      woman, treated 10 years ago for stage III cervical carcinoma. She received both
      intracavitary brachytherapy and external teletherapy. Since irradiation patient
      suffered from the stress urinary incontinence (SUI). She was diagnosed in our
      department and underwent successful anti-incontinence surgery. Because of
      oncological history and urodynamic parameters (markedly lowered closing urethral
      pressure) she was assigned to intravaginal slingplasty transobturator (IVS-OT)
      procedure with delayed positioning of the tape. There were no intra- or
      postoperative complication. The check-up done four months following surgery
      revealed that patient have full control of micturition and markedly improved
      quality of life.

PMID- 16417099
TI  - [Bernard-Soulier syndrome during pregnancy: a case report].
AB  - The Bernard-Soulier syndrome (B-S s.) is rare autosomal recessive bleeding
      disorder. It is characterized by prolonged bleeding time, fail to agglutinate
      with ristocetin and a normal to decreased number of unusually large platelets
      whose membrane lack glycoproteins complex GP Ib/IX/V. The manifestation of the
      disease may differ in consecutive pregnancies of the same patient. Presently we
      describe 24 years old white women diagnosed with B-S s. at the age of 22. Two
      years later she become pregnant. During the pregnancy platelet counts ranged from
      26 x 10(9)/1 to 51 x 10(9)/1, without sings of bleeding. Because of the risk of
      immunization against GP Ib/IX, with might lead to severe isoimmune neonatal
      thrombocytopenia, 4 times during pregnancy she had done MAIPA-test (monoclonal
      antibody immobilization of platelet antigens). Specific antibodies were not
      detected. Subsequent ultrasounds with biophysical profile revealed normal fetus
      growth. Spontaneous labour in 38th week of gestation. The use of single-donor
      platelets, intravenous desmopressin and tranexamic acid was found to be useful in
      controlling postpartum vaginal bleeding in the patient.

PMID- 16417101
TI  - [Angiogenesis-prognostic factor in patients with endometrial cancer].
AB  - Endometrial carcinoma is one of the most commonly found cancers. In numerous
      kinds of cancers, tumor microvessel density correlates with clinical stage of
      disease and is considered as an independent prognostic factor. Evaluation of
      angiogenesis intensity in endometrial cancer also seems to be an independent
      prognostic factor and statistically correlates with FIGO stage of disease,
      histological type and grade of tumor, depth of myometrial invasion and
      metastasis. Activity of angiogenic factors in human tissues and serum provides
      additional reference concerning the growth and progression of endometrial cancer.

PMID- 16417100
TI  - [Fetal cardiac defects in pregnancy complicated by diabetes mellitus].
AB  - Diabetic pregnancy cause a lot of complications where fetal malformation is one
      of the most serious. Cardiac defects are besides the neural tube ones the most
      often in this group of pathology. Lack of pregnancy planning and thanks to it
      hyperglycemia during conceptive period and early embryogenesis increases the risk
      of fetal defect. We describe some typical cardiac malformation and functional
      disturbances connected with fetal heart. In our research we show the basic scheme
      of obstetrical fetal echocardiography and some common diagnostic problems we meet
      during our examinations. In conclusion references were reviewed which described
      the new approach for clinical assessment of the fetal heart like 3D and STIC; and
      the early diagnostic fetal echocardiography turn of the 1st and 2nd trimester.

PMID- 16417102
TI  - Craniectomy for middle cerebral artery infarction.

PMID- 16417103
TI  - Visual impairment in the elderly.

PMID- 16417104
TI  - The glaucomas.

PMID- 16417105
TI  - Diabetic eye disease.

PMID- 16417106
TI  - Age-related macular degeneration.

PMID- 16417107
TI  - Visual loss as a result of age-related cataract.

PMID- 16417108
TI  - Clinical audit.

PMID- 16417110
TI  - Interpretation of the abdominal radiograph: 2.

PMID- 16417109
TI  - A broad complex tachycardia.

PMID- 16417111
TI  - Metacarpal and phalangeal injuries.

PMID- 16417112
TI  - How to perform an arteriovenous fistula.

PMID- 16417113
TI  - Delirium.

PMID- 16417114
TI  - So you want to be... an orthopaedic surgeon.

PMID- 16417116
TI  - Non-pharmacological treatment of arrhythmias.

PMID- 16417115
TI  - Bivalirudin: role in current percutaneous coronary intervention practice.

PMID- 16417117
TI  - General practice in the foundation programme: evaluation of a brief embedded
      experience.

PMID- 16417118
TI  - Superior mesenteric artery syndrome in a young girl following spinal surgery for
      scoliosis.

PMID- 16417119
TI  - Panda eyes and heart failure.

PMID- 16417120
TI  - Craniectomy for middle cerebral artery infarction.

PMID- 16417121
TI  - Coexistent gout and rheumatoid arthritis: a case report.

PMID- 16417123
TI  - New retirement planning opportunities.

PMID- 16417122
TI  - Gulf War illness.

PMID- 16417124
TI  - Who should transfer children with an acute neurosurgical emergency?

PMID- 16417125
TI  - Chemical partitioning to foliage: the contribution and legacy of Davide Calamari.
AB  - BACKGROUND: Davide Calamari and his colleagues were among the first to appreciate
      that vegetation could play a key role in determining the fate and effects of
      organic contaminants. They conducted pioneering experiments to investigate the
      uptake of contaminants by plants from the atmosphere and they sought to model the
      observed phenomena. In the nearly two decades since there has been a marked
      increase in understanding of these phenomena as a result of both experimental and
      modelling studies. GOAL: In this study we briefly review our current
      understanding of chemical partitioning between foliage and air. A model in both
      fugacity and concentration format is described, based on that of Tolls and
      McLachlan (1994), in which the leaf is treated as consisting of two layers, a
      waxy cuticle with an underlying 'reservoir' layer, the cuticle being surrounded
      by an air boundary layer and containing stomata that provide direct access from
      the air to the 'reservoir'. The model quantifies the dynamic penetration of a
      defined chemical into a defined leaf as a function of time. MAIN FEATURES: The
      model is applied for illustrative purposes to a hypothetical but typical leaf for
      a set of illustrative chemicals to demonstrate the effect of changes in physical
      chemical properties and leaf characteristics. DISCUSSION: The results are
      compared qualitatively with a variety of field and laboratory studies of foliage
      uptake and clearance of chemicals. CONCLUSION: It is concluded that the model
      yields results that are generally consistent with observations. It is suggested
      that with appropriate parameterisation and validation, the model can contribute
      to an improved understanding of the process of foliage uptake from the atmosphere
      and to the development of an improved predictive capability.

PMID- 16417126
TI  - The evolution of the Environmental Quality concept: from the US EPA Red Book to
      the European Water Framework Directive.
AB  - BACKGROUND: Water Quality Criteria were firstly defined in the 1970s by the EPA
      in the USA and the EIFAC in Europe, recognizing the need for protecting water
      quality in order to allow the use of water resources by man. In the 1990s, the
      European Commission emphasized the importance of safeguarding structure and
      function of biologic communities. These approaches were chemically-based. The
      European Water Framework Directive (WFD) substantially changes the concept of
      Water Quality, by assuming that a water body needs to be protected as an
      environmental good and not as a resource to be exploited. In this frame, the
      biological-ecological quality assumes a prevailing role. MAIN FEATURES: The Water
      Quality concept introduced by the WFD is a challenge for environmental sciences.
      Reference conditions should be defined for different typologies of water bodies
      and for different European ecoregions. Suitable indicators should be developed in
      order to quantify ecological status and to define what a 'good' ecological status
      is. Procedures should be developed for correlating the deviation from a good
      ecological to the effects of multiple stressors on function and structure of the
      ecosystem. The protection of biodiversity becomes a key objective. In this frame,
      the traditional procedures for ecotoxicological risk assessment, mainly based on
      laboratory testing, should be overcome by more site-specific approaches, taking
      into account the characteristics and the homeostatic capabilities of natural
      communities. In the paper an overview of the present knowledge and of the new
      trends in ecotoxicology to get these objectives will be given. A procedure is
      suggested based on the concept of Species Sensitivity Distribution (SSD).
      RECOMMENDATIONS AND PERSPECTIVES: The need for more site-specific and
      ecologically-oriented approaches in ecotoxicology is strongly recommended. The
      development of new tools for implementing the concept of 'Stress Ecology' has
      been recently proposed by van Straalen (2003). In the same time, more 'cological
      realism' is needed in practically applicable procedures for regulatory purposes.

PMID- 16417127
TI  - Pharmaceuticals in the environment in Italy: causes, occurrence, effects and
      control.
AB  - BACKGROUND, AIM AND SCOPE: Environmental contamination by pharmaceuticals is an
      emerging issue. Until recently, information on medicinal substances released into
      the environment was scant, but several studies have now been published. Data are,
      however, usually scattered and a systematic approach to this subject is generally
      lacking. Moreover, because of differences in the prevalence of diseases,
      treatment habits and options, or simply for market reasons, the pollution profile
      can differ significantly in different countries. The aim of this work is to
      review the papers dealing with environmental contamination by pharmaceuticals in
      Italy, with the aim of providing a comprehensive view on a national scale.
      METHODS: Papers related to environmental contamination by pharmaceuticals in
      Italy were reviewed, in order to offer a comprehensive view of this subject.
      Topics included analysis, occurrence, monitoring, modelling, treatment, control
      of the emissions, and ecotoxicological effects of pharmaceuticals in the
      environment. RESULTS AND CONCLUSION: The literature suggests that pharmaceuticals
      are widespread contaminants, entering the environment from a myriad of scattered
      points. Patients, in case of drugs for human use, or animals for veterinary
      drugs, are the main sources of contamination. Pharmaceuticals can be ranked
      according to environmental loads, predicted by multiplying sales figures by the
      rate of metabolism in man or animals. Priority pharmaceuticals, i.e. the
      molecules of concern for the environment, can be measured in waste and surface
      water by liquid chromatography-tandem mass spectrometry, and the loads detected
      are generally comparable to the predicted ones. Pharmaceuticals are designed to
      stimulate a response in humans and animals at low doses, with a very specific
      target, so the implications for human health and the environment need to be
      assessed. In vitro and in vivo studies suggest that pharmaceutical principles,
      taken singularly or in combinations, and concentrations close to those detected
      in the environment, may have ecotoxicological effects. The sewage system is an
      important point in the control of contamination, but sewage treatment plants are
      not able efficiently to abate a substantial part of water-borne pharmaceuticals.
      Several variables play a role, however, in the processes of waste water
      treatment, and could be specifically adjusted to improve the efficiency of drug
      abatement, mitigating the potential environmental hazards. RECOMMENDATION AND
      PERSPECTIVE: Pharmaceuticals in the environment are becoming a subject of global
      concern, with potential environmental consequences. Further knowledge of the
      causes, occurrence and effects of drugs as environmental pollutants is necessary
      for a better understanding of this ecological issue, as well as to improve
      abatement strategies, and to mitigate subtle environmental consequences.

PMID- 16417128
TI  - Toxicity of selected pharmaceuticals to the anostracan crustacean Thamnocephalus
      platyurus: comparison of sublethal and lethal effect levels with the 1h
      Rapidtoxkit and the 24h Thamnotoxkit microbiotests.
AB  - BACKGROUND, AIMS AND SCOPE: In view of the limited amount of information on the
      potential hazard of the ever increasing amounts of drugs in surface waters to
      aquatic biota, a study was undertaken to determine the effect levels of 28
      selected pharmaceuticals to the crustacean test species Thamnocephalus platyurus.
      The drugs belong to 5 different groups: non steroidal anti-inflammatory agents,
      biocides, cardiovascular compounds, nervous system drugs and pu rine alkaloids
      METHODS: Toxicity tests were carried out with the 1h Rapidtoxkit and the 24h
      Thamnotoxkit microbiotests in order to make a comparison of sublethal effects
      (visible as stress through absence of feeding) measured after a very short time
      of exposure (1h) and lethal effects after prolonged exposure (24h). Dilution
      series starting at 200 mg l(-1) were prepared and applied, and median effects
      levels were calculated and transformed into Toxic Units (TU) for easy data
      comparison. RESULTS AND DISCUSSION: The toxic effects found have been ranked into
      4 arbitrary toxicity classes: not toxic (TU<0.2), low toxicity (0.2<TU<1.0),
      toxic (1.0<TU<10) and very toxic (TU>10). The toxicity levels noted ranged from
      virtually no effects for a few of the pharmaceuticals, at the highest
      concentration tested out, to LC50's below 1 mg l(-1) (>100 TU) for 3 nervous
      system drugs (Amitryptiline, Thioridazine and Chlorpromazine). According to the
      toxicity classification, 17 of the 28 compounds (i.e. 67%), belong to the same
      class for the lethal and the sublethal tests. More pronounced differences in
      effect levels between the two assays were observed mainly for the pharmaceuticals
      which were either not toxic or only slightly toxic at the 200 mg l(-1) level. For
      90% of the toxic drugs the ratio between the toxicity values for both tests is
      below 5. CONCLUSION: An overall correlation coefficient of 0.96 was found between
      the 2 microbiotests, confirming the good predictive potential of the 1h stress
      based Rapidtoxkit in revealing important biological effects (mortality) after
      more prolonged exposure of the crustacean test species to chemical compounds.
      RECOMMENDATION AND OUTLOOK: The present study clearly shows that new
      microbiotests such as the 1h Rapidtoxkit and the 24h Thamnotoxkit are attractive
      tools for rapid cost-effective screening of 'new' pollutants such as drugs which
      may threaten the biological communities of the aquatic environment.

PMID- 16417129
TI  - Analysis of mosses and soils for quantifying heavy metal concentrations in
      Sicily: a multivariate and spatial analytical approach.
AB  - BACKGROUND: The use of vegetal organisms as indicators of contamination of the
      environment is partially replacing traditional monitoring techniques. Amongst the
      vegetal organisms available, mosses appear to be good bioindicators and are used
      for monitoring anthropogenic and natural fall-out on soils. This study has two
      objectives: the evaluation of the concentrations of heavy metals in soils and
      mosses of the Sicily Region, in Italy and the identification of the origin of
      fall-out of heavy metals. METHODS: Mosses and the surface soil were sampled at 28
      sites, only the youngest segments of Hylocomium splendens and Hypnum
      cupressiforme, corresponding to the plant tissues produced during the last 3
      years, were taken. The elements Cd, Cu, Ni, Pb and Zn were analysed by ICP-MS and
      Hg by AAS. Statistical analysis was by PCA and spatial representation by GIS.
      RESULTS AND DISCUSSION: In the mosses sampled in Sicily, the highest
      concentrations of Cd were found around the cities of Palermo and Messina. The
      highest concentrations of Hg were recorded in the northern part of the island
      between Trapani and Messina, similar to the distribution of Cu. Different areas
      with the highest concentrations of Ni were found near the south coast, in the
      vicinity of Palermo and around the Volcano Etna. The highest concentrations of Pb
      were found in the south-west coast near Agrigento, where important chemical
      plants and petroleum refineries are located. Except for a few locations, Zn fall
      out was found to be evenly distributed throughout Sicily. CONCLUSION: The sites
      where the concentrations of heavy metals cause greatest concern have been
      revealed by the PCA analysis and portrayed using GIS. Also of some concern is the
      diffuse and anthropogenic origin of Hg and Cd. The combined approach of using
      soil and mosses, together with pedological interpretation and application of
      multivariate statistical techniques has provided valuable insight into the
      environmental aspects of heavy metal deposition in a region of southern Europe.
      RECOMMENDATIONS AND OUTLOOK: Further insight into the deposition of heavy metals
      will require more detailed sampling of soils and mosses in both new and previous
      study areas. This needs to be complemented by detailed pedological investigations
      in the study areas. Future research programmes will address these issues.

PMID- 16417130
TI  - Water security in Uzbekistan: implication of return waters on the Amu Darya water
      quality.
AB  - GOAL, SCOPE AND BACKGROUND: Amu Darya river, one of the main water resources of
      Uzbekistan, shows a relevant longitudinal enrichment of soluble contents which
      strongly limits the human uses of its waters. Because of the low natural run-off
      processes, salts and pollutants are mainly driven to the river by the return
      waters used for washing and irrigating the surrounding lands. The influence of
      return waters on stream quality is dramatically relevant in the lower reaches of
      the river where almost all the flowing waters have been previously used for the
      agriculture practises. To provide analytical evidence on the potential effects of
      return waters on the quality of the Amu Darya river, the paper reports and
      comments data on salinity and metals contents of the waters flowing in the
      artificial channel network of Bukhara and in the Amu Darya river, from Bukhara up
      to the dam forming the Tuyamuyn Hydro Complex (THC). METHODS: A total of 15
      sampling sites were selected for the analytical survey: Two sites were located on
      the Amu Darya river downstream from the inflow of the return waters from Bukhara,
      two in the river entering in the THC, and three downstream from the dam forming
      the reservoir complex. The waters entering and leaving the Bukhara agricultural
      area were sampled in two main collectors, while the waters flowing in the channel
      system were sampled in six distinct collectors. The following parameters were
      considered in the survey: pH, Oxygen, Hardness, Salinity, Conductivity, P-PO4(3
      ), P tot, N tot, N-NO3(2-), N-NO2-, COD, Ca2+, Mg2+, Fe, Mn, Zn, Cr, Cu, Ni, Cd,
      Pb. RESULTS AND DISCUSSION: Salt concentrations below 1000 mg/l were measured in
      the Amu Darya waters upstream to Bukhara. In the drainage system, salinity
      exceeds the palatability limit and reaches the maximum peak of 3200 mg/l in the
      outflow collector. Due to dilution effects, salinity returns to lower values (400
      700 mg/l) along the Amu Darya river downstream from Bukhara; calcium and
      magnesium resulted the major constituents of the overall salinity. No serious
      metal contaminations were detected in the waters entering and leaving the
      examined channel system. Differently, the Amu Darya waters upstream to the THC
      showed a relevant metal contamination, with Cr, Ni, Fe concentrations exceeding
      the limits for human consumption. In the downstream sites, located in the
      Tuyamuyn Hydro Complex and in the Amu Darya river flowing out from this
      reservoir, excluding Fe, all the examined metals showed lover concentrations and
      values below the normative limits. CONCLUSION: The direct human consumption of
      the lower Amu Darya waters is strongly limited by salinity and by metal
      contamination. Although the salinity of the return waters from the Bukhara
      drainage system results in above normal limits, no corresponding increases were
      measured in the Amu Darya river downstream from the return water inflow at the
      time of the survey. As for the metal contamination of the Amu Darya river, the
      survey revealed the presence of relevant sources of metal contamination
      downstream from Bukhara external to the agricultural drainage system. This
      contamination resulted in reduced sedimentation processes taking place in the
      limnetic zones of the Amu Darya river upstream to the dam forming the Tuyamuyn
      Hydro Complex. RECOMMENDATION AND OUTLOOK: To fully understand the longitudinal
      increase of Amu Darya salinity, an evaluation of the cumulative effects of the
      loads from the main agricultural areas is required, also by using mass-balance
      models. As for the metals, an investigation should be addressed to identify the
      anthropogenic sources of contaminations present in the lower Amu Darya region and
      the metal loads should be diverted.

PMID- 16417131
TI  - Environmental persistence of chemicals.
AB  - BACKGROUND: The hazard criterion of persistence as it applies to chemicals in the
      environment is reviewed and discussed. This quantity can not be measured directly
      in the environment, thus it must be estimated using models that synthesise
      information on chemical half-lives and partitioning properties, the nature of the
      environment and how the chemical is released into the environment. MAIN FEATURES:
      It is suggested that the preferred criterion is the average residence time of the
      chemical in the environment, i.e. conceptually the sum of the life-times of all
      molecules (attributable only to losses by degrading reactions) divided by the
      number of molecules. If all chemical fate processes are first order, this
      persistence is independent of the quantity of chemical introduced and whether
      introduction is steady- or unsteady-state in nature. It is shown that in a
      multimedia environment persistence is affected not only by degradation kinetics,
      but also by mode-of-entry and partitioning. For screening level purposes a Level
      II equilibrium model may be adequate but a Level III model is generally
      preferable for estimating the average persistence. If a distribution of
      persistences is required a dynamic Level IV model must be used. DISCUSSION: The
      implications for regulating chemicals on the basis of persistence are discussed.
      CONCLUSION: It is concluded that the preferred strategy is to use Level II, III,
      and IV models and that the use of only degradation kinetics or media-specific
      half-lives can be misleading and uneconomical.

PMID- 16417132
TI  - Development of a dynamic aquatic model (DynA Model): estimating temporal
      emissions of DDT to Lake Maggiore (N. Italy).
AB  - BACKGROUND, AIMS AND SCOPE: Most existing models used to describe the fate of
      chemicals in surface water and sediment generally consider a 'static scenario',
      in which a contaminant is discharged at a constant rate and environmental input
      parameters do not change during the simulation time. This approach is not
      suitable in environmental scenarios characterized by daily or periodic changes of
      several input parameters. The aim of this study is to estimate approximate
      emissions of DDT lo Lake Maggiore using a new surface water model, (DynA Model)
      that describes the fate of a chemical in a dynamic scenario. METHODS: The model
      is developed on the grounds of an existing and validated model (QWASI). A
      numerical solution was adopted to build the fully dynamic version of the model.
      RESULTS AND DISCUSSION: The model was applied to Lake Maggiore emitting DDT at a
      constant rate until steady-state was reached. Emissions were stopped and later
      sporadic 'pulse' emissions were added. This was done to calculate the amount of
      DDT needed to simulate concentrations close to those measured in water and
      sediments. This allowed the evaluation of the order of magnitude of emissions. An
      uncertainty analysis for sediment resuspension was also performed, given the lack
      of measured resuspension rates. CONCLUSION: The model showed the time response of
      the Lake Maggiore system to varying emission scenarios and provided what are
      regarded as reasonable estimates of DDT emissions. The model demonstrated the
      importance of sediment-water exchange. RECOMMENDATION AND OUTLOOK: In order to
      better calculate DDT concentrations the model should be run with different
      discharge scenarios to clarify the time trends of concentrations, possibly with
      the use of different sets of measured data (such as biota and sediment
      deposition/resuspension rates).

PMID- 16417134
TI  - Polychlorinated biphenyls (PCBs) in mussels along the Chilean coast.
AB  - GOAL, SCOPE AND BACKGROUND: Chile signed the Stockholm Convention, which
      establishes measures to reduce or eliminate Persistent Organic Pollutants (POPs)
      release into the environment, including the prohibition of their use and
      reduction of secondary products release, as well as management related with waste
      treatment. Among POPs, PCBs are a family of 209 compounds that differ in chlorine
      level and position. These substances present a wide variability in their
      physicochemical properties such as vapor pressure, water solubility and partition
      coefficients that determine their behavior and mobility within the different
      environmental compartments. In Chile, as in other countries, the use of these
      compounds were and continue to occur in diverse industrial applications such as
      dielectric fluid in transformers and condensers, with a use in Chile of
      approximately 550,000 L. A sampling of bivalves was performed during the years
      2000-2002 in order to obtain information on the spatial distribution of the PCB
      levels for the length of the long Chilean coast (18 degrees-54 degrees South
      latitude, 4,200 km), contributing in this way to a better understanding of the
      PCB trend and eventual fractionation along latitudinal gradients in Chile, using
      as the bivalve Perumytilus purpuratus ('Chorito Maico') bioindicator. METHODS:
      The marine bivalves Perumytilus purpuratus were collected in 16 localities in
      northern and southern Chile. All samples were lyophilized, and PCBs (51
      congeners) were extracted in a Soxhlet system (24 h) with n-hexane. Samples were
      cleaned in florisil and analyzed by GC-ECD. Blanks, certified reference materials
      and standards were processed along with the samples. RESULTS AND DISCUSSION: The
      results obtained for P. purpuratus indicate a congeneric distribution profile
      associated to a latitudinal gradient, and the statistical analysis of the
      congeneric composition of the PCBs indicated five groups in relation to the
      molecular weight (number of chlorines), where the lighter congeners were observed
      in areas corresponding to high latitudes with total PCB values of 298 ng/g dry
      weight. CONCLUSION: P. purpuratus turns out to be a good bioindicator of PCB
      levels in the coastal areas of Chile due to its wide distribution. The highest
      concentrations and the more volatile congeners were found in southern Chile,
      which could be the result of processes of long-range transport or illegal
      discharge occurring in such remote areas. These results confirm previous data
      from the International Mussel Watch project ten years ago. RECOMMENDATION AND
      OUTLOOK: Future studies are needed to confirm our findings utilizing another
      environmental matrix such as soil/sediments and air samples.

PMID- 16417133
TI  - Pp'DDT and pp'DDE accumulation in a food chain of Lake Maggiore (Northern Italy):
      testing steady-state condition.
AB  - BACKGROUND, AIMS AND SCOPE: Although pp'DDT usage was strongly limited or banned
      in most parts of the world during the last three or four decades, the parent
      compound, its homologues and their metabolites still occur at levels which might
      pose a risk for many ecosystem components. A case of DDT pollution of industrial
      origin was discovered in 1996 in Lake Maggiore, the second largest (212 km2) and
      deepest (370 m) lake in Italy, causing concern for wildlife and human health. The
      extensive monitoring of many biotic and abiotic compartments which followed from
      1998 in order to assess the pollution level and its trend in time, provided a
      great availability of data referring to DDT contamination of the different fish
      species of the lake. In this study, the recent contamination levels in selected
      fish species were compared to those measured in 1998 to evaluate the temporal
      pollution trend of the lake and its natural recovery, given that no remediation
      measures were carried out on the contaminated soils and sediments in this time
      span. Moreover, a modelling approach to test the equilibrium condition between
      water and pelagic fish species was used. Analytical results of pp'DDT and pp'DDE
      concentrations in lake water were used as input data in the bioenergetic model by
      Connolly & Pedersen (1988) to calculate concentrations in two fish species and to
      compare the predicted and the measured contamination. METHODS: Sampling and
      analytical determination of DDT homologues in lake water: Five water sampling
      campaigns were carried out from May 2002 to February 2004 in three sampling sites
      of Lake Maggiore. Suspended and dissolved pollutants were determined separately.
      Quantitative DDT homologue analyses were performed by HRGC coupled with ECD
      detection by the external standard method. Single water extracts were put
      together in correspondence with the stratification zones of the water column
      inferred on the basis of the temperature profile to improve analytical
      sensitivity. Selection of fish data: Concentrations of DDT and DDE in fishes were
      selected from recent literature (CIPAIS 2003, 2004). Bioaccumulation model: The
      bioenergetic model proposed by Connolly & Pedersen (1988) was used to assess the
      bioaccumulation of pp'DDT and pp'DDE of Alosa fallax (landlocked shad) and
      Coregonus spp. (whitefish), selected among the different species as
      representative of a secondary consumer level. RESULTS AND DISCUSSION: The average
      concentrations of pp'DDT and pp'DDE in water to be used as input data in the
      bioenergetic model were obtained considering all the concentrations measured at
      the three sampling stations in the epylimnion where the fish species considered
      in this study spend most of their life. The resulting values were 0.05 and 0.16
      ng/L for pp'DDT and pp'DDE, respectively. Average measured pp'DDT and pp'DDE
      concentrations in landlocked shad were 0.81 +/- 0.39 and 1.69 +/- 0.71 mg/kg
      lipids, respectively, and were 0.29 +/- 0.12 and 1.06 +/- 0.41 mg/kg lipids for
      the whitefish. Calculated and measured values turned out to be in quite good
      agreement for pp'DDT, while measured pp'DDE concentrations were higher than
      expected on the basis of the bioenergetic model in both species. Probably
      metabolic transformations of pp'DDT accumulated in fish tissues in the past are
      responsible for the observed differences between calculated and expected pp'DDE
      concentrations in fish. CONCLUSIONS: Pelagic fishes of Lake Maggiore seem to
      maintain the DDT accumulated during their life time and the most efficient
      mechanism responsible for the fish population recoveries is probably their
      generation changes; for this reason, equilibrium models cannot be used until
      negligible pp'DDT concentrations are reached in fish tissues. RECOMMENDATIONS AND
      OUTLOOK: The limit proposed for pp'DDT in water by the EU Directive 2000/60,
      which will come in force in 2008, is 0.2 ng/L, four times higher than the average
      concentration measured in Lake Maggiore waters. Nevertheless, concentrations
      measured in Lake Maggiore fish were very close and sometimes exceeded the Maximum
      residue limits (MRLs) settled by the Italian legislation for foods (0.1 mg/kg
      w.w. for fish containing 5-20% lipid). It seems, therefore, that the
      'environmental quality standard' of 0.2 ng/L cannot guarantee the suitability of
      fish for human consumption.

PMID- 16417135
TI  - Reevaluating Harris lines--a comparison between Harris lines and enamel
      hypoplasia.
AB  - This study examines the association between Harris lines and enamel hypoplasia.
      This association is analyzed in terms of: 1) presence/absence of these markers in
      each individual, and 2) age of the individuals at the time of Harris lines and
      enamel hypoplasias formation. Data from two archaeological groups (Azapa-71 and
      Azapa-140) from northern Chile were analyzed. The results indicate Harris lines
      and enamel hypoplasias are not associated in terms of presence/absence. Moreover,
      the estimated age of the individuals at the time of Harris lines and enamel
      hypoplasia formation shows that these two markers have a very different
      distribution. While enamel hypoplasias clustered between ages 3 and 5, Harris
      lines were more commonly formed during the first year of life, as well as during
      adolescence, which are the periods of most accelerated growth. We propose that
      Harris lines are a result of a normal, rather than abnormal, saltatory growth
      process.

PMID- 16417136
TI  - Variations of femoral condyle shape.
AB  - The aim of this study is to mathematically approximate the shape of the femoral
      articulating line and compare radiuses of condylar curves within and between
      males and females. Ten male and ten female participants were included in the
      study. Radiuses of medial and lateral condylar curves were calculated from the
      side view knee X-ray by original mathematical equation. Average radiuses of
      condylar curves were between 4.5 and 1.7 cm medially, and between 3.2 and 1.8 cm
      laterally, for 0 degrees and 90 degrees flexion contact point respectively. Males
      had longer curve radiuses of both condyles (p < 0.05). Differences turned out to
      be statistically insignificant after adjusting to body height. Even small changes
      in the joint geometry during lifetime could make a joint susceptible to
      osteoarthritis or injuries. Approximation of the radiuses of femoral condyle
      curves is a useful method in anthropometric, radiological and virtual
      calculations of the knee geometry, and other ellipsoidal structures in human
      body, like wrist, scull segments, dental arches, etc.

PMID- 16417137
TI  - Visualizing facial shape regression upon 2nd to 4th digit ratio and testosterone.
AB  - Sex steroids are supposed to moderate the differences between male and female
      facial characteristics. Studies on women's preferences for male faces reported
      increased preferences for facial architecture developed under the influence of
      testosterone as this may indicate masculinity, dominance and social status.
      Recent research demonstrates that facial sexual dimorphism does not only develop
      at puberty but may be organized much earlier in ontogeny. However, the actual
      cause and timing of variation in facial shape due to sex-steroids remains
      speculative. This study uses data from Neave and colleagues who measured digit
      ratio (2D:4D) as a proxy to prenatal testosterone and also salivary testosterone
      samples in order to study differential effects of androgens on perceived male
      facial shape. Male facial shape was regressed upon 2D:4D ratio and circulating
      levels of testosterone by means of geometric morphometric methods. We found some
      evidence for opposite effects of early androgen action (via 2D:4D ratio) on the
      upper and the lower face respectively (i.e. low 2D:4D ratio results in a
      relatively robust and prominent lower face), whereas circulating testosterone
      seems to cause a rather uniform elongation of the face. Local deformations
      primarily show pronounced and medially tailed eyebrows for the shapes associated
      with increasing salivary testosterone. These preliminary results suggest that
      prenatal and pubertal testosterone have differential effects on male facial shape
      that should be considered in future studies on women's preferences towards male
      facial appearance.

PMID- 16417138
TI  - Dental arch relations analysed in a 14th century fossil skull of the Sao tribe,
      Cameroon.
AB  - Dental occlusal relations are rarely reported in paleo-anthropology. The
      manipulation of hemi-arch replicas, as well as the superimposition of drawings on
      calques traced from photographs, facilitated the description of the intra- and
      interarch relations. The occlusal interarch confrontation and the intermolar
      relation were observed and assessed in the horizontal, frontal and sagittal
      planes. Some measurements were helpful in the functional study. On the basis of
      knowledge in mandible kinematics a movement envelope of the first molar
      displacement during mastication was proposed. The dentition studied here was
      highly regular. It was a fine example of balanced wear for post-canine sectors.
      In spite of the lower canine extrusion, due to tribal mutilation of anterior
      teeth and to subsequent labret wearing, the interarch relations seemed not to
      have been altered.

PMID- 16417139
TI  - The influence of incompetent lip seal on the growth and development of
      craniofacial complex.
AB  - Abnormal orofacial functions in the period of growth and development can cause
      morphological anomalies of the craniofacial complex. The aim of this study was to
      determine the correlation between open mouth posture and morphology of
      craniofacial complex. The shape, size and relationships of skeletal parts of
      craniofacial complex were determined by analysis of lateral cephalograms in the
      sample of 84 children--45 girls and 39 boys (aged 8.96 +/- 0.66 years). The
      sample was divided into two groups--lip competence and lip incompetence group.
      Differences in cephalometric values between observed groups were found. The
      values of inclination of lower central incisors (angle ILi/NB), interbasal angle
      (NL/NSL), angle between occlusal and mandibular plane and anterior lower facial
      height were significantly higher in the group with open mouth posture. It can be
      concluded that lip incompetence plays an important role in growth and development
      of craniofacial complex.

PMID- 16417140
TI  - Proinflammatory factors in saliva as possible markers for periodontal disease.
AB  - Studies have indicated that host inflammatory proteins, enzymes and indicators of
      bone metabolism present in saliva differ in different types of periodontal
      disease. However, the number of markers analyzed was limited and the effect of
      edentulousness was not examined. We measured the concentration of host
      inflammatory proteins: C-reactive protein (CRP), C3 and C4 complement components,
      alpha-2-macroglobulin (alpha-2M) and tumor-necrosis factor (TNF) in unstimulated
      saliva of 14 periodontally healthy (PH), 9 edentulous persons (EP), 10 patients
      with chronic periodontitis (CP) and 18 with aggressive periodontitis (AgP). TNF
      was below the level of detection in all samples except one. Edentulous persons
      and patients with CP had significantly reduced concentrations of CRP, C3 and
      alpha-2M. Edentulous persons and AgP patients had lower C4 concentrations. We can
      conclude that edentulous persons and CP patients have reduced salivary
      concentrations of host inflammatory proteins. These findings suggest that a
      reduction in host responsiveness might play a role in the pathogenesis of CP.

PMID- 16417141
TI  - Oral health status and temporomandibular disorders in multiple sclerosis
      patients.
AB  - Multiple sclerosis (MS) is an inflammatory disease of unknown etiology involving
      the central nervous system. Certain clinical manifestations affect the oro-facial
      region. Three in particular should be of interest to the dentist: trigeminal
      neuralgia, sensory neuropathy of the trigeminal nerve and facial palsy. The aim
      of this study was to determine the oral health status, the frequency of
      subjective symptoms and temporomandibular disorders (TMD) subtype according to
      Research diagnostic criteria for temporomandibular disorders (RDC/TMD) among MS
      patients. Examinees in this study were 50 patients suffering from MS, who were at
      least once treated during their disease in the Clinic Hospital Center, Rijeka,
      Clinic for Neurology. All examinees had to meet the diagnostic criteria for
      clinically and laboratory confirmed MS, according to Poser. The results show the
      difference in mean DMFT (decayed, missing, filled teeth) between MS and the
      control group. The number of decayed and missing teeth was higher, but the number
      of filled teeth was significantly lower in MS group. Eighty-two per cent of the
      subjects with MS had a least one symptom of dysfunction compared with 24% of the
      subjects in the healthy control group. In the present study, pain, the pain
      during mouth opening, the difficulty with mouth opening and temporomandibular
      joint (TMJ) sounds were more commonly reported in the MS group than in the
      control group. This study shows a statistically significant excess of dental
      caries and temporomandibular disorders among MS patients compared with the
      control group. These results suggest that MS is a possible etiological factor in
      temporomandibular disorders.

PMID- 16417142
TI  - The mortality of two groups of infants in Spanish rural region.
AB  - In this study the structure of the mortality of two groups of infants settled in
      the same environmental context is analysed: the comarca (a typical Spanish sub
      division of territory) of La Cabrera (province of Leon, Spain) between the years
      1880 and 1932. In this geographical region of the northwest of Spain two
      communities of infants from different origins are found in this time period. On
      the one hand, an autochthonous infant population from the births of the
      legitimately constituted families settled in this territory. On the other, an
      infant population represented by a group of children who were abandoned in a
      foundling hospital situated in a nearby city (Ponferrada) and who were sent to
      this rural "comarca" to be breast-fed by wet-nurses being paid certain quantities
      of money. The mortality rates and the seasonality of the deaths have been
      analysed for both the autochthonous and non-autochthonous children. Thus we have
      been able to test whether differences in the structure of mortality exist.
      Throughout the study, the possibility that these differences in mortality could
      be attributed to discriminative cultural factors, expressed through preferential
      care and/or attention and which show in the different models of infant mortality,
      is considered.

PMID- 16417143
TI  - A cross-cultural analysis of positive illusions and sport performance levels in
      American, Croatian, and Norwegian basketball players.
AB  - The present study examined the degree to which positive illusion is associated
      with sport performance in basketball players among 3 different cultures: The
      United States of America, Croatia, and Norway. Positive illusion is a cognitive
      characteristic that is common in mentally healthy individuals, and becomes
      especially important in the athletic arena. The model tested in this study
      depicts the level of positive illusion as the main predictor variable and the
      performance of the basketball players as the criterion variable. The Positive
      Illusion Sports Scale was used to measure the predictor variable while The
      Basketball Evaluation System was used to measure the criterion variable.
      Participants were 239 competitive male basketball players, 122 from USA, 57 from
      Croatia and 60 from Norway. Results showed that positive illusion was directly
      (positively) related to actual success and that these relationships were
      statistically significant and consistent with positive illusion as a theoretical
      construct for predicting behavior and success.

PMID- 16417144
TI  - Inbreeding depression in anthropometric traits among Telaga boys of Kharagpur,
      West Bengal, India.
AB  - Inbreeding depression in phenotypic variations as well as reproductive capacity
      was reported in animals. Depression of physical measurements in human beings
      especially among infants and adults due to inbreeding has also been reported all
      over the world. The present study is an attempt to examine the nature of
      inbreeding effect on growing children at each yearly age with increase of
      inbreeding intensity in a local endogamous population based on pedigree data. In
      general, mean values of measurements appear to be smaller in higher levels of
      inbreeding from that of lower levels of inbreeding in each yearly age. These
      differences are even more marked when grouped as low and high inbreeding level.
      The percent of inbreeding depression tends to be larger in post adolescent boys
      than in younger children.

PMID- 16417145
TI  - Ultrasonographic estimation of fetal weight--residents accuracy.
AB  - The aim of this retrospective study was to evaluate the accuracy of gynecology
      and obstetrics residents when performing ultrasonographic estimation of fetal
      weight. The total of 400 ultrasonographic estimations of fetal weight and
      corresponding neonatal weight were collected and divided into 3 groups according
      to physicians' experience (junior and senior residents, staff physicians). The
      accuracy of fetal weight estimation correlated positively with the level of
      physicians'experience. The proportional difference between ultrasound estimation
      and actual birth weight varied from 8.45% to 6.88% (junior residents 8.45%,
      senior residents 6.95%, staff physicians 6.88%). The proportion of
      ultrasonograhic estimates that fell within 10% of birth weight varied from 59.09%
      to 79.21% (junior residents 59.09%, senior residents 78.44%, staff physicians
      79.21%). Senior residents reach a highly acceptable accuracy in ultrasonographic
      estimation of fetal weight which is comparable to staff physicians.

PMID- 16417146
TI  - Estimating height from arm span measurement in Malawian children.
AB  - Arm span and standing height were measured in 289 boys and 337 girls aged 6-15
      years who were free from physical deformities which can affect stature or arm
      span. The arm span exceeded height in all age groups of boys and in older girls.
      At the age of 7, 11 and 12 years girls were significantly taller than the boys
      and had longer arm span while at the age of 15 years, the trend was opposite. The
      mean difference between the two anthropometric parameters for boys was 5.45 +/-
      4.21 cm (t = 3.556, p < 0.001) and for girls was 4.94 +/- 4.96 cm (t = 3.542, p <
      0.001). Correlation coefficient between height and arm span measurements for
      Malawian boys was 0.983 and for girls was 0.986. Height, arm span and height-arm
      span difference increased with age of children while height to arm span ratio
      decreased. The gender difference in height-arm span differences was only
      significant at the age of 15 years. Multiple regression and cross validation were
      performed. Height of Malawian children of both sexes can be estimated from
      equation: Height (cm) = 15.756 + (0.168 x age) + (0.839 x arm span) (SEE = 0.760,
      R2 = 0.988).

PMID- 16417147
TI  - Sources of infection in childhood tuberculosis in a region of east Croatia.
AB  - Possible sources of tuberculosis (TBC) infection in children have been assessed
      in a retrospective epidemiological study covering a north-east region of Croatia
      in which the incidence of childhood tuberculosis has been increasing since the
      war in 1991-1995. During the past decade (1993-2003), 271 children up to 18 years
      of age have been referred for hospital care because of known contacts with
      tuberculosis (142 children, group A) or because of indicative clinical signs and
      symptoms (129 children, group B). Possible sources of infection were identified
      on the basis of medical documentation and field investigations. Frequencies of
      source identification for different age groups were compared. In group A, the
      exposure took place most often within the family (parents, grandparents,
      siblings, 129 of 142 children, 90.87%). Relatives, neighbors, friends and
      schoolmates accounted for 9.2%. In group B, possible sources of infection were
      identified for 44 of 129 children (34.1%) and were within the family for 16 of
      those 44 (36.4%). Evidenced contact with tuberculosis was more usual among
      younger children (0-9 years of age, 65.5%) in group A than among the older ones
      (10-18 years of age, 34.5%). In group B, contacts with tuberculosis were equally
      distributed (50.0%) among younger and older children. High proportion of
      unrecognized contacts in children having clinical signs and symptoms indicative
      of tuberculosis (group B, 85 of 129, 65.9%) opens the possibility that extra
      familial exposure to tuberculosis occurs more often than expected regardless of
      the age of children.

PMID- 16417148
TI  - Associations between parental and child overweight and obesity.
AB  - Results of the analysis showed that parents and children overweight/obesity were
      significantly correlated. The sample includes 318 pairs of mothers and children,
      and 336 pairs of fathers and children at the age 11.3 +/- 0.4 years in Trogir,
      Croatia. Child overweight and obesity were defined according to body mass index
      (BMI) 25 and 30 equivalents (kg/m2). The prevalence of total overweight in girls
      was 25.6% and among boys was 20.5%. Mother's weight (p = 0.003) and BMI (p =
      0.006) were greater in obese than in other groups of children. Overweight/obese
      children were more often found among overweight/obese mothers (p = 0.009) and
      fathers (p = 0.039). Correlation between overweight/obese children and their
      father (odds ratio 3.2, 95% CI 1.5-6.8) was stronger than between
      overweight/obese children and their mothers (odds ratio 2.2, 95% CI 1.2-3.9).
      Associations with mothers' and daughters' overweight/obesity were stronger (p =
      0.017) than mothers' and sons'(p = 0.12). Correlations between children's BMI and
      fathers' BMI (r = 0.265, p < 0.0001) and between children's BMI and mothers' BMI
      (r = 0.173, p = 0.002) were significant. Children whose parents are
      overweight/obese look for greater attention in future preventive programme.

PMID- 16417149
TI  - Regional adiposity, body composition and central body fat distribution of 10-16
      years old Bengalee boys of Nimta, North 24 Parganas, West Bengal, India.
AB  - A cross-sectional study of 502 Bengalee boys aged 10-16 years of Nimta, North 24
      Parganas, West Bengal, India, was undertaken to study regional adiposity, body
      composition and central body fat distribution. The subjects were classified into
      seven age groups: 10-10.9 years (n = 74), 11-11.9 (n = 53), 12-12.9 (n = 87), 13
      13.9 (n = 116), 14-14.9 (n = 58), 15-15.9 (n = 57), 16-16.9 (n = 57). In general,
      there was a significant linear increasing trend from 10 to 16 years for all the
      anthropometric variables. There was a net increase of 30.5 cm and 22.8 kg in mean
      height and weight, respectively, between 10 and 16 years of age. Mean BMI
      increased by 3.7 kg/m2 during the same period. Among circumferences, the largest
      increase was in hip followed by chest while the smallest increase was in mid
      upper arm, between 10 and 16 years of age. Subscapular skinfold showed the
      largest increase followed by abdomen and suprailiac skinfolds, while the increase
      was least in forearm skinfold. Significant linear increasing trend was observed
      for all the body composition measures. The largest increase in percent of body
      fat (PBF) was observed between ages 10 and 11 years while mean fat mass (FM), fat
      free mass (FFM) and fat mass index (FMI) increased the most between 14 to 15
      years. However, an overall decreasing trend was observed, in mean waist-to-hip
      ratio (WHR) from 10 to 16 years. Boys aged 10 years had the highest mean WHR
      while those aged 15 years had the lowest mean WHR. There was an increase in mean
      WHR among 16 years old boys.

PMID- 16417150
TI  - Body composition and fat distribution pattern of urban elderly females, Delhi,
      India.
AB  - The present study was conducted on females (n = 279) in the age range of 51-89
      year, living in the urban dwellings of Delhi, India. Another group of 21-25 years
      old young adult females was taken as a control group. A total of 14
      anthropometric measurements were taken: stature, sitting height, weight, skinfold
      thickness at nine different sites over the body and body girths such as upper
      arm, waist and hip circumference. Indices like body mass index, grand mean
      thickness, waist-hip ratio were computed to assess the body composition. Fat
      profile and responsiveness of different skinfold sites towards fat accumulation
      were studied to find out the regional fat distribution with advancing age.
      Redistribution of body fat was found to take place with increasing age. A
      relative preponderance of upper body fat was visible among elderly subjects.
      However, a clear reverse trend was observed in the young control group females.
      Significant differences were observed with regards to the body composition and
      fat profile between young adult females and test group females. Abdomen and the
      sub-scapular area were reported to be the most sensitive sites for fat deposition
      as the age advanced. The stature and sitting height showed significant decline
      with age. All the indices of adiposity i.e. grand mean thickness, waist-hip ratio
      and body mass index revealed significant changes in elderly females when compared
      with young adult control group females.

PMID- 16417151
TI  - Validity of optical device lipometer and bioelectric impedance analysis for body
      fat assessment in men and women.
AB  - The aims of this study were to validate different subcutaneous adipose tissue
      layers (SAT-layers) measured by lipometer for body fat percentage (BF%)
      assessment with dual-energy X-ray absorptiometry (DXA) and to compare the
      validity of lipometer and bioelectrical impedance analysis (BIA). The subjects
      were 21 male (18-60 years) and 19 female (23-54 years) healthy Estonian
      volunteers. SAT-layers were measured by lipometer using 15 standardized SAT
      layers. Sum of arms, legs and trunk SAT-layers were calculated and compared with
      arms, legs and trunk fat percentage measured by DXA. BF% was calculated by BIA
      using the equations of Lukaski et al. and Chumlea et al. for both genders and the
      equations of Segal et al. for males and Van Loan and Mayclin for females. BF%
      measured by DXA was significantly higher than calculated by Lukaski et al. and
      Chumlea et al. in both genders. The correlation was highest between the BF%
      measured by DXA and using Segal et al. equation in males (r = 0.94) and Van Loan
      and Mayclin equation in females (r = 0.84). High relationship was observed
      between BF% measured by DXA and sum of 15 SAT-layers (r = 0.88 in males and r =
      0.91 in females). Stepwise multiple regression analysis indicated that two
      selected SAT-layers explained 85.9% and 86.7% (R2 x 100) of the total variance in
      BF% measured by DXA in males and females, respectively: [BF% = 1.308 neck + 0.638
      hip + 6.971 (males; SEE = 2.59) and BF% = 1.152 hip + 1.797 calf + 12.347
      (females; SEE = 3.46)]. In conclusion, lipometer and BIA give a similar mean
      estimation of BF% when compared with DXA. However, there is a wide range of
      variance for the upper and lower limits of agreement between the methods, and the
      methods are not interchangeable. Lipometer seems to be superior to BIA.

PMID- 16417152
TI  - Calcium intake, food sources and seasonal variations in eastern Croatia.
AB  - The objective of this study was to examine the quantity of calcium intake among
      adults, the sources of calcium, differences among seasons, as well as the
      differences between sexes, correlation with body mass index (BMI), and age. The
      study included 161 healthy volunteers from the eastern part of Croatia. Each
      subject completed three food frequency questionnaires (FFQ) with 150 items, at an
      interval of 3-4 months. The mean calcium intake for whole population for all
      three FFQs was 965 mg/day. At the same time, the quantity of calcium for all
      subjects was 14.2 mg/kg, women 14.5 mg/kg, and men 13.6 mg/kg, respectively.
      There was an inverse relation between calcium intake and age for men (r = -0.32 p
      = 0.028), but not for women. Correlation between calcium intake and BMI was
      negative, but not significantly. Milk and dairy products were the main source of
      calcium. Marginally low mean calcium intake goes to show the needful to educate
      the population.

PMID- 16417153
TI  - The effectiveness of a 40-year long iodine prophylaxis in endemic goitre region
      of Grobnik, Croatia.
AB  - The region of Grobnik, in the north west of Croatia, 15 km away from the Adriatic
      coast and 400 meters above the sea level, used to be known as a centre of endemic
      goitre. Iodine prophylaxis of 10 mg KJ added per kilo salt started in Croatia
      during the year 1953 and it was increased to 25 mg KJ per kilo in 1996. During
      1961, the prevalence of goitre among Grobnik school children was 63%, while in
      the adult population it was 34%. In 1981, 18% of goitrous school children and 11%
      of goitrous adults were found in the same region, which shows the fall in goitre
      prevalence in the twenty-year period, from a severe to a mild one. The aim of
      this study was to estimate the effectiveness of iodine prophylaxis in goitre
      eradication and to compare the obtained results to those found in the same region
      20 and 40 years ago, namely, in 1961 and 1981. The research was conducted in
      2001. We examined 472 Grobnik inhabitants, 378 children (196 girls and 182 boys,
      aged 7-15 years) and 94 adults. Regarding their size thyroid glands were graded
      according to WHO and PAHO classification. Data regarding lifestyles and health
      conditions were collected by individual and family questionnaires. The prevalence
      of goitre in 2001 was 6.6% in school children and 6.4% in adults. In relation to
      1981, we found a statistically significant fall of goitre in school children at
      the level of p < 0.01 (chi2 = 23.65), but the prevalence change was not
      statistically significant in adults (p > 0.01, chi2 = 1.419). The frequency of
      thyroid gland hereditary diseases in native inhabitants was high, 11.7%. There
      were no statistically significant differences in the prevalence of goitre or
      thyroid hereditary diseases between groups of native and newcomers' children.
      According to our results, in the year 2001 the area of Grobnik was still was a
      region of a mildly expressed endemic goitre. This study presents final results of
      a 40-year long follow up of endemic goitre eradication, demonstrating the long
      term effectiveness of iodine prophylaxis.

PMID- 16417155
TI  - Epidemiological study of suicide in Croatia (1993-2003)--comparison of
      Mediterranean and continental areas.
AB  - The aim of this study is to analyze eventual differences in characteristic of
      suicide between two areas of the Republic of Croatia, mediterranean and
      continental, according to the following variables: suicidal rates, season, month,
      day, method, places, socioeconomic variables such as gender, ages, marital
      status, employment, education, and psychiatric or medical characteristic. Data
      were collected from the Suicide register of the Ministry of Interior, and
      Croatian Bureau of Statistic. Analysis was done on all suicide cases committed in
      the period 1993-2003. According to the Suicide Register of Ministry of Interior,
      11,359 suicides were reported in period between 1993 and 2003. The average
      suicide rate in the Mediterranean area was lower (16.44 suicides per year) than
      in continental area of Croatia (26.34 suicides per year). Suicide committers in
      the Mediterranean area was statistically significant younger than suicide
      committers in the continental area of Croatia. In the continental area male
      suicide committers were more often than in the Mediterranean area of Croatia. In
      the Mediterranean area suicide committers were in most cases with high school
      education while in continental area of Croatia most cases of suicide committers
      were with elementary school education. Alcohol dependence, family conflicts, and
      medical disorders were more often present as suicidal motive in suicide
      committers in continental area of Croatia than in the Mediterranean area where
      undefined and unknown reason of suicide is present in majority of suicide cases.
      Cold steel, drowning, and jumping from height were more often present as suicidal
      method in the Mediterranean area of Croatia opposite to continental area of
      Croatia where jumping in front of car or train and suicide with firearms and
      explosive were more often. Also, in the Mediterranean area of Croatia suicides
      was mostly committed on open spaces and public places while in continental area
      of Croatia suicides was mostly committed in private plot.

PMID- 16417154
TI  - Mood effects of weather conditions of the Zagreb population, Croatia.
AB  - The level of information on biometeorologic reports and mood effects of weather
      conditions on the Zagreb population were assessed in a sample of 782 subjects.
      Only 103 (13.2%) study subjects had not been informed on biometeorologic reports.
      Mood effects of weather conditions were reported by more than 76% of study
      subjects, 18.3% of them reporting meteorosensitivity. Meteorosensitivity showed a
      female predominance, and increased with age and level of education. 88% of
      chronic patients reported discomforts caused by changes in atmospheric
      conditions. Apathy and sleepiness were the most common mood changes associated
      with weather changes, whereas humid weather was indicated as a weather type that
      caused most discomforts in study subjects.

PMID- 16417156
TI  - Suicidal thought and behavior in high school students in Adana, Turkey.
AB  - Fifty years ago adolescents mostly died of natural causes, whereas they now die
      from more preventable causes. Part of this change has been a worldwide rise in
      adolescent suicide rates in both developed and developing countries. Suicides are
      probably under reported due to cultural and religious stigma attached to self
      destruction. Objectives of this study were to collect data about suicidal
      thoughts, plans and attempts and related sociodemographic details in high school
      students. The population comprised 2,480 randomly selected students among 46,271
      students from 72 high schools in 1999-2000 in Adana and 2,352 (94.8%) students
      from 10 schools were reached and given a questionnaire modified using Youth Risk
      Behavior Survey Questionnaire (YRBSQ). Chi2 and Kolmogorov-Smirnov tests were
      used. Mean age was 16.5 +/- 1 (14-21) year, 1,187 (50.5%) students reported
      severe desperation, 526 students (22.4%) had suicidal thoughts, 332 (14.1%)
      planned committing suicide, 145 (6.2%) attempted suicide. The occurrence rate of
      desperation, suicidal thoughts, plans, attempts and the mean number of attempts
      were significantly higher in females than males. Adolescent suicide is a tragedy
      affecting individual, family, peers, and community. Families, teachers, and
      physicians should be aware of risk factors for suicide.

PMID- 16417157
TI  - Influence of alcohol abuse of the father on the intensity of clinical picture of
      posttraumatic stress disorder.
AB  - The subject of the study is the influence of alcohol abusing father on the
      clinical picture of PTSD patient. The father plays an important identification
      role in the psychological development of his son. Therefore it is to be expected
      that an alcohol abusing father will become a (negative) role model for his son
      and that he will also later on in stressful situations try to reduce the anxiety
      and depression by consuming larger quantities of alcoholic drinks. The aim of the
      study is to find out whether there are differences in PTSD clinical picture in
      patients whose fathers abused alcohol and in those whose fathers did not have
      such problem. The participating patients were from the Psychiatric hospital
      "Sveti Ivan". Mississippi and Watson scales were applied, as well as a
      questionnaire named "Early traumas" from which the variable "alcohol abuse of the
      father" was selected. The analysis shows that the participants who in their
      family histories had fathers who abused alcohol developed a milder clinical
      picture of PTSD, i.e. they reactions to the stress later on were less sensitive
      compared to the control group of participants whose fathers did not abuse alcohol
      and whose clinical pictures of the disorder were more severe.

PMID- 16417158
TI  - The mental health of children upon their return home after a long displacement
      period.
AB  - The aim of this study was to determine the different levels of depression,
      hopelessness and post-traumatic stress disorder between two groups of
      adolescents, those who returned to Baranja and those from Osijek. The first group
      consisted of 57 adolescents (32 female and 25 male) with the mean age of 17.36,
      who were grammar school students in Beli Manastir (Gimnazija, Beli Manastir). The
      mean duration of displacement period was 7 years. The second group consisted of
      58 adolescents of grammar school students in Osijek (III. gimnazija, Osijek) (32
      female and 26 male) with the mean age of 17.28. All examinees filled in the
      Croatian version of the Children's Depression Inventory (CDI), the Hopelessness
      Scale for Children (HSC) and Children's Post-Traumatic Stress Disorder (PTSD)
      Inventory. The analysis of the results did not show any statistically significant
      difference between these two groups regarding levels of depression, hopelessness
      and post-traumatic stress disorder. The results point out rather good
      psychosocial adjustment of adolescents upon their return home after 4 years.

PMID- 16417159
TI  - Implementation of first Croatian Law on Protection of Persons with Mental
      Disorders.
AB  - The aim of this article was to examine Croatian psychiatric practice regarding
      involuntary hospitalization, after the Law on Protection of Persons with Mental
      Disorders became effective, on January 1, 1998. Data on the practice of
      involuntary hospitalizations of patients with mental disorders in Vrapce
      Psychiatric Hospital were collected from the medical records, for the years 1998
      and 1999. Data regarding involuntary hospitalizations from other Croatian
      hospitals and departments were obtained from heads of psychiatric hospitals and
      departments for the first five months of 1998. The rate of involuntarily
      hospitalized patients in Vrapce Psychiatric Hospital rose significantly from 1998
      to 1999 (p < 0.01). The rate of patients involuntarily hospitalized under section
      21, subsection 3 rose significantly from 1998 to 1999 (p < 0.01), while rate of
      patients involuntarily hospitalized under section 22, subsection 1 decreased
      significantly in the same period (p < 0.01) in Vrapce Psychiatric Hospital. The
      implementation of the Law on protection of persons with mental disorders was not
      applied uniformly in all Croatian psychiatric institutions during first five
      months of 1998. Further analyses on this subject are necessary in order to
      investigate the influence of changes and supplements to the Law on the protection
      of persons with mental disorders on the practice of involuntary hospitalizations.

PMID- 16417160
TI  - Changes of defense mechanisms and personality profile during group analytic
      treatment.
AB  - Researching efficiency of group-analytic treatment and following Foulkes'
      principle of the "group-as-a-whole", the methodology was applied. That enabled
      the evaluation of expected changes of group members individually, as well as the
      group-as-a-whole. In this study three small groups (20 patients) were followed up
      and changes were evaluated after second and after fourths years of group
      analysis. Two measuring instruments--The Life Style Index and Defence Mechanisms
      Scale (LS-DM) and Minnesota Multiphase Personality Inventory (MMPI-201) were
      applied. Each member of the group was assessed by self-evaluation as well as the
      group-as-a-whole. The results of the research indicated that changes of the
      personality occurred. Changes consisted in lowering of defensive activities that
      was tending towards more mature defences. Changes also consisted in lowering
      ratings on the pathological parts of the MMPI-scales reflecting shifting of the
      conflict level. The results could be predictive for positive outcome of group
      analysis. More studies are needed.

PMID- 16417161
TI  - Morbidity and mortality in the city of Zagreb, Croatia--health needs and demands.
AB  - The aim of the study was to assess health indicators in the city of Zagreb in
      order to evaluate the population health status and health needs. A descriptive
      method was used to analyze data from regular health statistics. In the population
      of Zagreb, the life expectancy at birth is longer than the European average but
      shorter than that recorded in Austria and Slovenia. The standardized mortalitay
      rates of tracheal, bronchial and lung cancer, and of malignant diseases in the
      Zagreb population exceed the European average, whereas those of ischemic heart
      disease, cerebrovascular disease, uterine cervix carcinoma and breast cancer are
      lower than the European average. Circulatory diseases and neoplasms, the two most
      important groups of death causes, showed a constant rise during the 30-year
      period (1971-2001). The highest index of primary health care utilization (98.8%)
      was recorded for the > or = 65 age group, with a mean of 7.5 primary health care
      visits per capita. The prevalence of hypertensive disorders and of intervertebral
      disk diseases and other dorsopathies was significantly higher in the oldest
      population group (chi2 = 27.3 and chi2 = 13.43, respectively, p < 0.05 both).
      Considering the predominance of chronic widespread diseases that substantially
      influence the patient's quality of life, public health actions should primarily
      be focused on preserving personal autonomy of the old and sick man for as long as
      possible. As the standardized mortality rates of ischemic heart disease,
      cerebrovascular diseases, tracheal, bronchial and lung cancer, and malignant
      diseases exceed those reported from some neighboring countries, the highest
      priority and needs are now related to coping with unhealthy behavior of the
      population such as smoking, physical inactivity, and dietary issues that should
      be modified and controlled through implementation of preventive programs, along
      with appropriate organization and management of public health services.

PMID- 16417162
TI  - Effects of smoking and alcohol consumption on vertebral deformity in the elderly-
      an epidemiological study.
AB  - The aim of the study was to assess the role of smoking and alcohol consumption as
      possible risk factors for vertebral deformities in an elderly Croatian population
      sample. Data on smoking habit, alcohol consumption, body mass index, and overall
      life activity were collected in 425 randomly chosen community dwelling subjects.
      Radiographic morphometric method was used to assess vertebral deformities of
      thoracic and lumbar spine. Men smoked and drank significantly more than women.
      There was no association of either smoking status or number of cigarettes, or
      frequency of alcohol intake with prevalent vertebral deformities. There was a
      tendency of an increased risk of vertebral deformities in heavy drinkers (OR =
      1.69; 95% CI = 0.98-2.91), and a reduced risk of these deformities in female
      regular drinkers (OR = 0.72; 95% CI = 0.14-3.66). Further studies in the Croatian
      population are needed to establish the association of smoking and alcohol
      consumption with vertebral deformities.

PMID- 16417163
TI  - Influence of the war in Croatia on the frequency of gynecological cancer in the
      University Hospital Osijek in the period from 1985 to 2002.
AB  - The aim of this study is to estimate the influence of war in Croatia on the
      frequency of gynecological cancer (cancer of corpus and cervix uteri and ovary)
      in the Clinical Hospital Osijek, particularly the relation between the pre-war
      and post-war period. We analyzed 1455 patients with corpus uteri and cervix uteri
      cancer and ovarian cancer treated in the Clinical Hospital Osijek in the period
      1985-2002 (group I). Patients from Osjecko-Baranjska County were analyzed
      separately--1273 women, (group II) and in the group III there were 182 patients
      from other counties. The analyzed period was divided into: pre-war 1985-1990, war
      1991-1993 and post-war period 1997-2002. In all three groups the number of
      patients treated for gynecological cancer was significantly larger in the post
      war period (group I, N = 611, group II, N = 498, group III, N = 113) than in the
      pre-war period (group I, N = 457, group II, N = 433, group III, N = 24). The
      analysis of cancer frequency in relation to the site shows that a total number of
      patients treated for cervical cancer was larger in the post-war (N = 229) than in
      the pre-war period (N = 214), but the difference wasn't significant. However, the
      number of patients from Osjecko-baranjska County treated for cervical cancer was
      larger in the pre-war (N = 207) than in the post-war period (N = 178) but still,
      the difference wasn't significant. The number of patients treated for corpus
      uteri cancer and ovarian cancer was significantly larger for the I group in the
      post-war (N = 225 and N = 157 respectively) than in the pre-war period (N = 136,
      and N = 107 respectively). In the group II the number of patients treated for
      corpus uteri cancer and ovarian cancer was larger in the post-war (N = 196 and N
      = 124 respectively) than in the pre-war period (N = 130 and N = 96 respectively)
      but the difference was significant only for corpus uteri cancer. Significantly
      more women were treated for gynecological cancer in the post-war than in the pre
      war period. However, the war had probably an indirect influence on the increased
      number of patients treated for gynecological cancer mainly because many more
      women arrived from other counties.

PMID- 16417164
TI  - Patients review: drug-induced movement disorders.
AB  - Objective of this paper is to review drug-induced movement disorders (D-IMD)
      treated patients on Department of Neurology in University Hospital Osijek. We
      reviewed patients treated during 10 years period (from 1992 to 2002). Analysed
      group consisted of 14 patients. Reasons for hospitalisation were swallowing
      problems in 6 patients, neuroleptic malignant syndrome (NMS) in 3 patients,
      stroke in 2 patients, bolus choking in 2 patients, and speech disturbance in 1
      patient. Working diagnosis for most of our patients was neurological disease, yet
      only later D-IMD diagnosis was established excluding primary neurological
      disease, or as associated disease to basic neurological disorder. Nine patients
      have diagnosed as Parkinson syndrome, 3 patients as NMS, and 4 as orolingual
      dyskinesia, either autonomously, or in combination with Parkinson syndrome. D-IMD
      was most frequently caused by neuroleptics. Thus the small number of patients
      hospitalised regarding this syndrome on Department of Neurology.

PMID- 16417165
TI  - Gemcitabine in the first and second-line chemotherapy of advanced non-small cell
      lung cancer.
AB  - Aim of this study was to estimate efficacy of gemcitabine in first and the second
      line chemotherapy for patients with advanced non-small cell lung cancer (stage
      III and IV). In first-line chemotherapy, 120 patients were treated with different
      chemotherapy regimens. Fifty-nine patients were treated with gemcitabine /
      cisplatin (PG), 41 with cisplatin / etoposide (PE) and 20 with mitomycin /
      ifosfamide / cisplatin (MIC). Forty patients, unsuccessfully treated with PE and
      MIC in first-line therapy were treated with PG (24 pts) and with best supportive
      care (BSC) (16 pts). In first-line therapy PG was superior to PE and MIC protocol
      (mean survival (MS) 10 vs. 7 vs. 8.5 months). Response rate (RR) for PG in first
      line therapy was 46% and 21% in second-line. We showed also significantly better
      survival in patients treated with PG in second-line chemotherapy comparing to
      best supportive care (MS 9 vs. 5.5 months). Toxic side effects for combination PG
      was acceptable. This study confirmed that PG combination is safe and effective as
      first and second-line chemotherapy for patients with advanced non-small cell lung
      cancer.

PMID- 16417167
TI  - Migrations in clinical and pathological stage of prostatic carcinoma in patients
      undergoing radical prostatectomy in the period between 1993 and 2003.
AB  - The aim of this study based on an analysis of personal material was to establish
      stage migration in a relatively large number of patients who had undergone
      radical retropubic ascendant prostatectomy (RRP). Between 01.07.1993. and
      31.06.2003. RRP was performed in 801 patients at the urology department of the
      Kliniken-Essen-Mitte. Data regarding diagnostic workup, treatment and
      postoperative course were collected prospectively into a database. An analysis
      was made regarding clinical and pathological stage and numbers of patients with
      positive lymph nodes. During the observation period the number of radical
      prostatectomies increased significantly from 8 in 1993 to 130 in 2002. The number
      of organ-confined tumors increased continuously between 1997 and 2003. In
      contrast to this, advanced and metastatic tumors showed a continuous decrease
      from 76% in 1997 to 66% in 2002. Between 1994 and 2003 the number of T1c tumors
      increased by 20%. Introduction of systematic 12-cylinder biopsy (S12C) increased
      the detection of prostatic carcinoma by 38% and the number of diagnosed tumors of
      a lower clinical stage increased. These facts confirm a trend towards clinical
      and pathological stage migration resulting from extensive use of prostate
      specific antigen (PSA) and S12C biopsy in the diagnosis of prostatic carcinoma.

PMID- 16417166
TI  - Changes in bone mineral density in patients with prostate cancer treated with
      androgen deprivation therapy.
AB  - Osteoporosis is a complication of permanent androgen deprivation in men with
      prostate carcinoma, following either bilateral orchiectomy or treatment with GnRH
      agonists. The present approach to the problem of osteoporosis includes
      prevention, adequate follow-up and appropriate treatment as an imperative of
      contemporary urological and endocrinological management of these patients. Bone
      densitometry was performed in 18 patients who were on GnRH agonists treatment
      during 1-3 years. The patients under therapy were followed clinically, PSA
      (prostate-specific antigen) values were determined and bone scintigraphy was
      performed. The bone mineral density values in 13 patients indicated osteopenia,
      whereas in one patient the finding was compatible with osteoporosis. Four
      patients had normal bone mineral density findings. Bone densitometry should be
      performed before initiation of treatment with GnRH agonists in order to quantify
      the therapy-related bone loss. Prevention of development of osteoporosis and its
      complications depends on the assessment of pharmacological treatment in this
      group of patients, including e.g. bisphosphonates and possible intermittent
      androgen deprivation.

PMID- 16417168
TI  - Choice of age cut-off for endoscopy in dyspepsia in developing countries
      according to incidence of gastric cancer.
AB  - Endoscopic examination of all patients with dyspepsia is hard to perform, because
      of high annual prevalence of dyspepsia and limited resource availability,
      especially in developing countries. Aim was to establish age cut off for upper
      endoscopy in dyspeptic patients without alarming features according on incidence
      of gastric cancer in western Herzegovina in Bosnia and Herzegovina. Group of 2697
      (1536 males, 1161 females) patients over 15 with chronic dyspepsia without
      alarming features and symptoms of gastroesophageal reflux disease, had been
      referred for a diagnostic upper endoscopy during 4 years. Study was prospective.
      All 34 gastric cancers were diagnosed in male patients above 55 years, and in
      female ones above 60. In the same age groups two thirds of gastric ulcers were
      found out. If the age cut off for dyspeptic patients had been 55 years for male
      and 60 for female gender, the workload could be decreased by 50%. The choice of
      alternative approaches is possible, depending on the level of diagnostic
      uncertainty, the patient and his physician are prepared to accept. Age cut off
      determines diagnostic approach in chronic dyspepsia, and greatly decreases the
      endoscopy workload.

PMID- 16417169
TI  - The amputees and quality of life.
AB  - The application of highly sophisticated computer technology and high technology
      materials allows production of quality prosthetic replacements both in the
      functional and esthetic sense. The basic prerequisite for successful use of
      prostheses is an adequately shaped stump, which can be achieved using new
      operative technique used for extremity amputation. In this way, the possibilities
      of prosthetic device usage are enlarged to fulfill not only basic daily needs but
      also highly active work-related, sports-related or recreational needs of the
      modern man. However, the adequate and successfully performed operative procedure
      and the implementation of a quality prosthetic device do not guarantee that all
      patient requirements for improved quality of life are fulfilled. The aim of this
      study was to examine therapeutic effects of the applied method of surgical and
      prosthetic treatment, with a special focus on the improvement of patient's
      quality of life. The research was conducted in a sample of healthy and active
      patients with trauma-related lower extremity amputation. Following a positive
      objective evaluation by the physician, who stated that surgical and prosthetic
      treatment was satisfactory, the subjective evaluation was performed by the
      patient using a specially designed questionnaire. The factors possibly
      influencing the overall satisfaction of the patient with therapy were analyzed.
      The satisfaction with prosthesis function was evaluated as very good by 63.5% of
      the patients, excellent by 9.6% and good by 26.9% of the patients.

PMID- 16417171
TI  - Patients' satisfaction with prosthetic devices.
AB  - The purpose of the paper was to ascertain the factors which affect the
      satisfaction of patients with the prosthetic therapy. The purpose of the paper
      was also to ascertain if there are common factors characteristic for patients
      dissatisfied with the prosthetic therapy although the specialist appraises it as
      objectively successful. 52 patients of the Clinical Institute for Rehabilitation
      and Orthopedic Devices were participating in the research, to which, after
      unsuccessful surgical-prosthetic rehabilitation, reamputation and prosthetic
      provision was carried out, which was appraised successful by the doctor. It was
      endeavored to appraise to what extent the appraisal by the doctor corresponds to
      patient's satisfaction. On the basis of the questionnaire elaborated specifically
      for this research and the statistical processing, it was concluded that where the
      doctor appraised the prosthetic therapy as successful, the same opinion was
      shared by the majority of the patients (92.3%). Patients are similarly satisfied
      with the function and the esthetic quality of the prosthesis (73%). The reason
      why 7.7% of patients are dissatisfied in cases when the doctor considers that
      there are no objective reasons for that should be sought in non-medical factors.
      The age, the education, the marital status, the income state, the size of the
      residence and the regional affiliation do not have a significant influence on the
      satisfaction of patients with the prosthesis (p > 0.05). Patients with a minor
      handicap achieve satisfaction with the prosthetic therapy faster, as well as the
      right-handed persons if the prosthesis on the right-hand extremity is in question
      (p < 0.05). This investigation showed that the responsibility of not wearing
      prosthetic aids, both orthopedic, and dental prostheses, couldn't be only
      neuroticism by prosthetic patients, because that connection is not statistically
      significant (p < 0.09).

PMID- 16417170
TI  - Socio-demographic characteristics and lifestyle habits of pregnant women smokers.
AB  - The aim of this study was to describe anthropometric, clinical, socio-demographic
      characteristics and lifestyle habits of pregnant smokers in comparison to
      pregnant nonsmokers. During years 1999-2003, 1,435 pregnant smokers and 4,772
      pregnant nonsmokers were interviewed after delivery with a questionnaire. They
      were recorded clinical, anthropometric and socio-demographic data, smoking
      status, labor outcome, maternal and fetal hemoglobin concentrations for each
      patient. The two groups were comparable in anthropometric and clinical
      characteristics, duration of pregnancy and mode of delivery, except for birth
      weights, which were significantly lower in newborns of smokers. Maternal
      hemoglobin concentrations were significantly lower in smokers, but fetal
      hemoglobin concentrations were significantly higher in babies of smokers. The
      proportion of pregnant women who smoked during pregnancy was higher among urban
      women, among women with lower educational level and among unemployed subjects in
      comparison with nonsmokers. The pregnant women who smoked during pregnancy were
      more often caffeine and alcohol consumers. To further reduce smoking during
      pregnancy it is important to continue to promote smoking cessation among
      teenagers.

PMID- 16417172
TI  - The dissections of craniocervical arteries.
AB  - Dissection of craniocervical arteries internal carotid artery (ICA), or vertebral
      artery (VA) is an increasingly recognized entity and infrequent cause of stroke.
      We investigated 8 patients (4 women and 4 men) with dissections of the
      craniocervical arteries. Diagnostic procedures for detection of craniocervical
      dissection included: extracranial ultrasound-color Doppler flow imaging (CDFI) of
      carotid and vertebral arteries, transcranial Doppler sonography (TCD) and
      radiological computed tomography (CT) and digital subtractive angiography (DSA)
      examinations. Ultrasound findings (CDFI of carotid and vertebral arteries) were
      positive for vessel dissection in seven patients (or 87.5 per cent) and negative
      in one patient. DSA was consistent with dissection in five patients (or 62.5 per
      cent), negative in one, while in two patients the examination was not performed
      due to known allergy to contrast media. Five patients (62.5 per cent) were
      treated with anticoagulants, one with suppressors of platelet aggregation, and
      two patients were operated. Six patients (75 per cent) after the treatment showed
      partial recovery of neurological defects, and an improvement of ultrasound
      finding of dissected arteries. In one patient, following operation, stroke
      developed with deterioration of motor deficit, and one patient was readmitted
      three months later due to a newly developed stroke and soon died. The diagnosis
      should be suspected in any young or middle-age patient with new onset of
      otherwise unexplained unremitting headache or neck ache, especially in
      association with transient or permanent focal neurological deficits.

PMID- 16417173
TI  - Carotid bifurcation position and branching angle in patients with atherosclerotic
      carotid disease.
AB  - Carotid artery bifurcation (CB) is the preferred site for development of
      atherosclerosis (AS) in extracranial cerebral arteries; internal carotid artery
      stenosis is the most common cause of ischemic stroke. The frequent
      atherosclerotic disease of CB may best be explained by the hemodynamic influence
      of complex blood flow that results from the unique geometry of the bifurcation.
      Few papers analyze all possible geometric structural characteristics of this
      bifurcation. While performing many carotid endarterectomies, we noticed that a
      certain correlation between CB height in the neck and its angle existed, that a
      larger angle is accompanied with increased frequency of elongation and kinking
      and that CB shape influences distribution of atherosclerosis. The purpose of this
      paper is to quantify and evaluate these clinical observations. Radiogrametric
      analysis of 154 bi-plane orthogonal aortic arch arteriograms of patients with
      symptomatic atherosclerotic carotid artery disease was performed and a total of
      289 CBs were analyzed. The CB height in relation to cervical spine segments was
      measured and real angles of each bifurcation were calculated. A positive linear
      correlation between CB height and angle exists: the CB angle increases /decreases
      3.34 degrees for each third of the cervical vertebral body height or
      intervertebral space height. The CB is positioned a little higher on the left
      side. The proximal border of the atherosclerotic process is found at the level of
      intersection of the axes of the common carotid artery branches in 92.6% of
      examined CBs. In lower CBs (with smaller angles) the proximal border was located
      in the last segment of the common carotid artery, while in high bifurcations
      (wider angles) the proximal border of the AS process is more distally in the
      blood flow, in the beginning of the internal carotid artery, and the process was
      more extensive. High CBs are more suitable for eversion endarterectomy while
      normal and low CBs are more suitable for open (classic) carotid endarterectomy.
      The influence of the geometric risk factor demands further investigation.

PMID- 16417174
TI  - The correlation of changes of the optic nerve diameter in the acute retrobulbar
      neuritis with the brain changes in multiple sclerosis.
AB  - The aim of this paper is to compare diameter of healthy and affected optic nerve
      determined by ultrasound with brain lesions in acute retrobulbar neuritis in
      patients with multiple sclerosis. In this prospective study 20 patients with
      multiple sclerosis and acute retrobulbar neuritis were examined. Optic nerve
      diameter was measured by ultrasound. Brain lesions were detected by magnetic
      resonance. Correlation between demyelinating lesions of the brain in multiple
      sclerosis and optic nerve diameter was tested by Kruskal-Wallis test. Significant
      difference in diameter between healthy and affected optic nerve in acute
      retrobulbar neuritis was found. Demyelinating brain changes examined by magnetic
      resonance revealed periventricular lesions, subcortical lesions and lesions in
      corpus callosum. There is statistically significant correlation between optic
      nerve diameter and number of brain lesions in multiple sclerosis, p < 0.05.
      Diameter of optic nerve in retrobulbar neuritis measured by ultrasound correlates
      with brain lesions detected by magnetic resonance in multiple sclerosis.

PMID- 16417175
TI  - Analysis of the quantitative dermatoglyphic traits of the digito-palmar complex
      in patients with primary open angle glaucoma.
AB  - Patient with primary open angle glaucoma (PAOG), which is known to have a genetic
      predisposition, and their immediate relatives unaffected with PAOG, may have some
      changes in dermatoglyphic traits of the digito-palmar complex, since the
      trabecular meshwork develops at the same time and with the same hereditary base
      like dermatoglyphs, which have high genetic transmission. The objective of this
      study is to determine whether differences in quantitative dermatoglyphic traits
      of the digito-palmar complex exist between patients with glaucoma and the
      phenotipically healthy population and whether their family members have the same
      dermatoglyphic changes. The quantitative dermatoglyphic traits in patients
      suffering from glaucoma, first-degree members of their family and the
      phenotypically healthy population have been screened in this study. Descriptive
      statistics, univariate analysis of variance (ANOVA) and post hoc (Tukey HSD)
      method have been used. The results have shown that there is a link between the
      quantitative dermatoglyphic traits of the digito-palmar complex in patients
      affected by glaucoma and a first-degree healthy member of their family, as well
      as the difference between patients with glaucoma and their first-degree
      relatives, which may discriminate them from the phenotypically healthy
      population. The results of the study mostly affirm the existence of genetic
      predisposition for the development of primary open-angle glaucoma, thus
      emphasizing the relevance of hereditary factors in the etiopathogenesis of this
      disease.

PMID- 16417176
TI  - Thrombus size is associated with etiology of deep venous thrombosis--a cross
      sectional study.
AB  - The aim of this study was to evaluate the impact of risk factors for deep vein
      thrombosis (DVT) on thrombus sizes in lower extremities. The size and extent of
      thrombus was scored according to International Consensus Committee for venous
      disease classification. After the diagnosis of DVT was established and its size
      scored, predominant risk factors for DVT in each patient were identified
      (malignant disease, thrombophilia, postoperative state, hormonal therapy,
      heredity, limb trauma, immobilization, others and unknown risk factors). The
      average thrombus score was 6 (95% CI 5.47-6.53). The analysis of thrombus size
      indicated that the largest thrombi were found in patients with malignancy. Their
      average score was 8.5 (95% CI 7-10) and was significantly higher than in patients
      with other risk factors for deep vein thrombosis. There was no significant
      correlation between numbers of days from the onset of symptoms to the moment of
      DVT diagnosis and thrombus score (r = -0.08, p = 0.38). Age was very slightly
      correlated to thrombus size (r = 0.19; p = 0.046), while the gender did not have
      significant impact on thrombus score (p = 0.074). The conclusion of our study was
      that etiology of thrombosis and particularly malignant diseases has the largest
      impact on venous thrombus size.

PMID- 16417177
TI  - The renal parenchyma evaluation: MAG3 vs. DMSA.
AB  - Scintigraphy with Tc-99m dimercaptosuccinic acid (DMSA) is considered a reference
      method for assessment of parenchymal lesions and estimation of differential
      kidney function. The aim of study was to evaluate Tc-99m mercaptoacetyltriglycine
      (MAG3) dynamic renal scintigraphy for the same purpose. 188 patients, submitted
      to both studies within three months, were divided in two groups. In the first, 83
      DMSA images were compared to parenchymal phase of MAG3 scintigraphy. Kidney
      morphology was independently evaluated by four observers. In the second group (N
      = 105), differential function was calculated in MAG3 and DMSA studies and the
      respective results were compared. Findings corresponded completely in 85% of
      patients. There were no statistically significant differences between calculated
      differential function on DMSA and MAG3 images. The results showed that most of
      parenchymal lesions detected on DMSA scans can be identified on MAG3 parenchymal
      scans. Both studies can be equally used for the calculation of differential
      kidney function.

PMID- 16417178
TI  - Epidemiology of Campylobacter jejuni and Campylobacter coli infections in the
      Zenica--Doboj Canton, Bosnia and Herzegovina--a laboratory based surveillance in
      the 1999-2001 period.
AB  - Previous studies in the Zenica--Doboj Canton, Bosnia and Herzegovina, indicated
      some different epidemiological features of Campylobacter infections and high
      degree of antimicrobial resistance. Therefore, it was important to investigate
      epidemiology of Campylobacter jejuni and Campylobacter coli infections by
      demographic features and antimicrobial resistance in the 1999-2001 period. A
      total number of 40 (75.5%) C. jejuni and 13 (24.5%) C. coli non-repeated clinical
      isolates were analyzed. More than half of isolates, 30 (56.6%) were from urban
      dwellers. Campylobacter isolates mainly obtained from children under 6 years of
      age, 42 (79.2%), resulting in far off highest incidence rate of 41.4/100,000/year
      in this age group. There was noted high degree of resistance to ciprofloxacin in
      children less than 6 years of age (14.3%), and extremely high overall
      erythromycin-resistance rate (30%). Campylobacteriosis in this region is a public
      health concern not in the term of the number reported cases, but of distinctive
      epidemiologic features.

PMID- 16417179
TI  - A comparison of lymphocyte subpopulations simultaneously on local and systemic
      levels in acute rheumatoid arthritis patients.
AB  - Rheumatoid arthritis (RA) is one of the most destructive inflammatory and
      autoimmune joint diseases, most frequently accompanied by extraarticular
      complications. The pathophysiologic mechanism and the importance of cell
      subpopulations in the initiation and perpetuation of synovitis are not
      sufficiently understood. In this study the frequency of lymphocyte subpopulations
      simultaneously in the synovial fluid (SF), the synovial membrane (SM) and
      peripheral blood (PB) of acute RA patients is determined, using flow cytometry
      procedures. The changes in the distribution of T lymphocyte subpopulations were
      significant on local levels in acute RA patients, resulting in a decreased
      CD4/CD8 ratio in SF, but an increased CD4/CD8 ratio in SM, compared to the ratio
      found in PB. The differences observed in the frequency of cells positive on
      natural killer (NK) cell markers suggest the role of CD16-CD56+ NK cell
      population in SF of RA patients. Significant differences in the observed
      frequency of lymphatic subpopulations suggest certain specificities of local
      immunological events in SM and SF in acute RA. These results confirm the T
      lymphocyte hypothesis in initial pathogenic events in RA.

PMID- 16417180
TI  - Poaceae pollen concentrations in the atmosphere of three inland Croatian sites
      (2003-2004).
AB  - The aim of the study was to determine the length of Poaceae pollen season,
      intradiurnal, daily and monthly pollen variation, and the effect of some
      meteorological parameters on atmospheric pollen concentration, at three
      monitoring sites in inland Croatia during the 2003-2004 period. Seven-day Hirst
      volumetric pollen and spore traps were used for pollen sampling. At all three
      monitoring sites considerably higher precipitation and lower average temperature
      in 2004 led to a marked decrease in the grass pollen concentration in the air at
      all three monitoring sites. The highest grass pollen concentrations were recorded
      in Ivanic Grad (typical rural area), considerably lower in Samobor (effect of
      forest vegetation), and lowest in Zagreb (urban area). The highest atmospheric
      Poaceae pollen concentrations in inland Croatia were generally recorded in May
      and June. The highest intradiurnal concentrations were recorded between 8.00 and
      12.00 a.m. Results of this aeropalynologic study are expected to help in
      preventing the symptoms of allergic reaction in individuals with Poaceae pollen
      hypersensitivity.

PMID- 16417181
TI  - Association between childhood atopic disease and parental atopic disease in a
      population with high consanguinity.
AB  - The aim of the study was to investigate the association between asthma, allergic
      rhinitis, and eczema in Qatari schoolchildren with allergic conditions in their
      parents. A cross-sectional study was conducted among 3500 Qatari schoolchildren
      aged 6-14 years in period: February, 2003-February, 2004. A questionnaire was
      used to collect the clinical history of asthma and allergic rhinitis in their
      parents and siblings. It was found that 21.6% of asthmatic children had mothers
      with asthma and 18.2% fathers with asthma. This contrasted with 6.8% of non
      asthmatic children who had fathers with asthma and 9.4% mothers with asthma. As
      for allergic rhinitis, 26.5% of asthmatic children had mothers with allergic
      rhinitis and 25.3% fathers with allergic rhinitis. The frequency of either parent
      of the asthmatic children having allergic rhinitis was 41.8% and for both parents
      was 10.0%. The frequency of siblings having asthma was 36.6%, allergic rhinitis
      16.4%, and eczema 29.1%. The present study revealed a strong association between
      respiratory allergies and eczema in parents, and their asthmatic children.

PMID- 16417182
TI  - Montelukast in asthma treatment in Croatia.
AB  - The aim of this study was to determine the efficacy and safety of montelukast
      added to previous medication in the treatment of a mild and moderate asthma. Data
      were obtained via questionnaires given to the physicians and given further to
      their patients. Patients were divided in two groups, first followed 4 weeks (612
      patients) and second followed 8 weeks (91 patients). We found out that there was
      a significant improvement in FEV1 (forced expiratory volume in first second) and
      general condition of patients and decreased number of salbutamol inhalations
      after using montelukast. In the second group of patients we find out the same
      significant improvement in FEV1, general condition and decrease in salbutamol
      inhalations after 4 weeks of using montelukast and further improvement after the
      next month of therapy. We conclude that montelukast is an efficient drug with
      little side effects and with a good compliance. Montelukast managed to achieve a
      good asthma control; therefore it has a significant place in asthma therapy.

PMID- 16417184
TI  - Effects of vanadate on glucose production in cultured hepatocytes isolated from
      rats on high saturated fat diet.
AB  - Insulin resistance is a common phenomenon in obesity and Type 2 diabetes. Common
      factor important for development of diabetes and insulin resistance is intake of
      saturated fat. Vanadate treatment improves glucose homeostasis in vivo. The aim
      of this study was to find out changing of hepatic glucose output in dependence of
      saturated fat diet and possible direct action of vanadate in cultured
      hepatocytes. Hepatocytes were isolated by a collagenase perfusion technique and
      cultured for 24 h in M 199 serum-free medium. The glucose production in
      hepatocytes isolated from rats on high saturated fat diet was significantly 139%
      higher comparable to standard controls. Glucagon 100% increased glucose
      production in hepatocytes from rats on standard diet and 200% in hepatocytes on
      saturated high fat diet. The addition vanadate significantly decreased basic
      glucose production and did not influence glucagon stimulated glucose production.
      Presence of insulin did not influence either glucagon or vanadate effect. High
      saturated fat diet not only increases insulin resistance but also decreases
      chances of successful therapy of diabetes.

PMID- 16417183
TI  - Met-enkephalin effects on histamine-induced bronchoconstriction in guinea pigs.
AB  - We investigated the effects of the neuropeptide met-enkephalin on histamine
      induced bronhoconstriction in an experimental model of asthma. Classic Konzett
      and Rossler's method of whole body plethysmography modified by Gjuris, was
      applied in the study. This method represents a standard experimental model of
      bronchoconstriction, suitable for the evaluation of peptide effects on the
      histamine-induced bronchoconstriction. The results of the measurements implicate
      a dose-related modulatory effect of met-enkephalin on the bronchoconstrictor
      action of histamine. Met-enkephalin doses of 1 mg/kg and 10 mg/kg, respectively,
      caused statistically significant reduction of the histamine-induced
      bronchoconstriction. Estimated ED50 dose was 0.235 mg/kg. Further studies are
      needed to define practical and therapeutical use of the presented observations in
      respiratory pharmacology.

PMID- 16417186
TI  - Some anthropologic characteristics of elite female handball players at different
      playing positions.
AB  - Differences in motor and psychologic variables according to playing positions
      were analyzed in a sample of 53 elite female handball players, members of junior
      and senior national team. Motor status included 8 variables for assessment of
      explosive strength of landing and throwing, agility, speed strength, movement
      frequency, and flexibility. Psychologic status was analyzed through 4 dimensions
      according to Eysenck: extroversion, psychotic behavior, neurotic behavior, and
      lie. The anthropologic features analyzed showed statistically significant
      differences. Considering motor abilities, differences were recorded in the
      variables for assessment of speed strength, agility and leg movement frequency,
      where wings predominated, whereas goalkeepers showed predominance in flexibility.
      In psychologic status, differences were present in the variable for assessment of
      extroversion, which was most pronounced in wings, whereas psychotic behavior was
      more expressed in those at pivot position. The differences were primarily
      consequential to the selection of players of a specific anthropologic profile for
      particular playing positions. The hypothesis of the impact of kinesiologic
      specificities of a particular playing position on the formation of the players'
      anthropologic profile should be scientifically tested. Study results may found
      application in training and contest practice, especially in forming anthropologic
      models for particular positions during the process of player selection.

PMID- 16417185
TI  - Anthropological determinants of success in young judoists.
AB  - There is an evident lack of experimental studies dealing with the anthropological
      determinants of success in judo, especially concerning young athletes. In this
      paper we have attempted to establish some of the anthropological factors
      potentially related to judo competition achievement in 15-16 year old athletes. A
      set of 14 anthropometric and 12 motor-endurance variables was tested on the best
      young judoists in Croatia (all males, N = 34). All the subjects had competed on
      the National Championship (NC), and the criterion was defined according to their
      final NC achievement. Factor analysis and discriminant canonical analysis
      (DISCRA) were calculated separately on the motor-endurance and anthropometric
      status variables. DISCRA showed the successful judoists as dominant in strength
      and endurance status. In contrast, there were no significant differences in the
      anthropometric dimensions regarding any differentiation between the more and less
      successful athletes. Possible explanations are discussed.

PMID- 16417187
TI  - Integration of coordination into the morphological-motor system in male children
      aged 7-11 years.
AB  - The study objective was to analyze the integration of psychomotor coordination
      into other dimensions evaluated. Four morphologic variables (stature, body mass,
      forearm circumference and triceps skinfold) and 7 motor variables (hand tapping,
      standing jump, sit-ups, forward bow, bent arm hang, 3-min run and polygon
      backward) were assessed in a sample of 2205 male children (subdivided into 4
      groups) aged 7-11 years, elementary school first- to fourth-graders from the
      Primorje - Gorski Kotar County, Republic of Croatia. Relations between the set of
      morphologic-motor variables and the coordination variable (of backward polygon)
      as a criterion were analyzed Data were processed by use of regression analysis.
      Study results clearly indicated the values of the criterion variable
      (coordination) to rise and the criterion prediction using the set of variables to
      improve with age. Explosive strength, movement frequency and static strength were
      the best positive criterion predictors, whereas body weight at age 7-10, and
      skeletal longitudinality and subcutaneous adipose tissue at age 10-11 were the
      best negative criterion predictors. Also, developmental characteristics of
      coordination were found to be a major determinant on programming the work in
      kinesiologic education of elementary school children.

PMID- 16417188
TI  - Effect of new rules on the correlation between situation parameters and
      performance in beach volleyball.
AB  - The aim of the study was to assess the effect of basic technical-tactical
      elements, i.e. specific motor abilities, on performance in beach volleyball, with
      special reference to differences between the old and new official rules. Analysis
      of variance for 6 variables of technical-tactical elements between the winning
      and defeated teams included a sample of 129 sets played according to the old
      official rules (1995 and 1996) and 74 sets played according to the new official
      rules (2003). This was followed by regression analysis between these technical
      tactical elements as predictors and a variable, i.e. score difference at which
      the team won or lost the game, as a criterion. Results of the analysis of
      variance between the winning and defeated teams showed highest differences in the
      performance of attack-hit, followed by counterattack-hit and blocking in both
      game types. However, difference in the performance of serve reception, serve, and
      field defense between the winning and defeated teams decreased significantly with
      the use of new rules as compared with the old ones. Results of regression
      analysis indicated the sets played according to the new rules relative to old
      ones to increase the predominant impact of technical-tactical elements in the
      above-net actions, especially attack-hit and block, on the final result in beach
      volleyball.

PMID- 16417189
TI  - Non linear relationships between anthropometric and motor-endurance variables.
AB  - Nonlinear regressions are rare in anthropology. In this paper we have tried to
      identify the significance and the character of the linear and non-linear
      relations between some anthropometric measures and the motor-endurance status.
      All subjects (300 moderately physically active males, mean aged 24 +/- 3.4 years)
      were measured for body weight, body height, body mass index, push-ups, sit ups,
      standing high jump, 50 meters swimming, and 1500 meters running. Linear (general
      model: y = a+bx) and nonlinear regression (general model: y = a+bx+cx2) was
      calculated simultaneously. According to the presented results the non-linear
      square relation between variables can be expected: a) if there is evident cause
      why two absolutely different sub-groups of subjects should reach equal results in
      the criterion, b) if a non-linear-square basis for the established relationship
      can be found. In conclusion, simple linear and non linear regression procedures
      are to be used for the identification of linear and nonlinear predictors in
      nonlinear multiple regressions.

PMID- 16417190
TI  - Causal Bayesian network for tagging syntactical structure of Croatian sentences.
AB  - Paper describes tagging syntactical structure of Croatian language sentences
      using causal Bayesian network. In the first part of the paper we describe
      Bayesian model for tagging sentences. Base on this idea, we will test our model
      on Croatian language sentences on Database of grammatical sentences of Croatian
      language (http://infoz.ffzg.hr / tepes /). This paper is result of our new
      research connected with the paper hidden Markov model for tagging of Croatian
      language texts for project Linguistic Analysis of The European languages and the
      paper Probability distribution on the parse trees for the project Annotated
      database and syntactic structure of Croatian languages.

PMID- 16417191
TI  - Probability distribution on the parse trees.
AB  - Paper describes probability distribution on the parse trees of natural language
      by using Bayesian networks. First parts of the paper describes probabilistic
      context-free grammar and parse trees. In the second part of the paper, Bayesian
      network was modelled and joint probability distribution on their vertex. On these
      theoretical ideas, in the third part, we describe our model tested on Database of
      grammatical sentences of Croatian language (http:/ /infoz.ffzg.hr / tepes /). At
      the end was presented a backward procedure and evaluation of our results.

PMID- 16417192
TI  - Comparison of fetal plasma cortisol level between eutrophic and hypotrophic
      newborns.
AB  - We tested two groups of singletons born at term: fifty-six eutrophic newborns and
      56 hypotrophic subjects. They were selected randomly from all newborns delivered
      by vaginal route between 8 and 14 hours. Excluded were preeclampsia, diabetes,
      labours longer than 12 hours and newborns with malformations. Written informed
      consent was obtained from all women and data were collected before and after
      labour. Umbilical cord blood samples were obtained immediately following the
      delivery and plasma cortisol concentrations were measured by radioimmunoassay.
      The groups did not differ significantly regarding maternal age, parity,
      gestational age and Apgar score, but birth weight was significant differed (p <
      0.001). In addition, eutrophic newborns had significantly elevated cortisol
      levels (457.7 nmol/L, 321.8-696.6 nmol/L) compared with hypotrophic newborns
      (320.5 nmol/L, 215.1-578.7 nmol/L, p < 0.001). The role of fetal cortisol in
      intrauterine growth restriction (IUGR) pregnancy and labour is uncertain, but
      fetal plasma cortisol levels may be lower in IUGR newborns.

PMID- 16417193
TI  - Septic acromioclavicular arthritis in a patient with diabetes mellitus.
AB  - A 44-year-old diabetic man with isolated septic arthritis of the left
      acromioclavicular joint (A-C) caused by Staphylococcus aureus is described. He
      was admitted to the Department of Rheumatology with clinical symptoms of left
      shoulder arthritis and fever. Laboratory findings showed leukocytosis, elevated
      levels of erythrocyte sedimentation rate and C-reactive protein, all indicating
      septic arthritis. Blood culture was positive for Staphylococcus aureus. Left A-C
      joint x-ray and ultrasonography, and whole body scintigraphy with 99 mTc
      radiolabeled autologous leukocytes pointed to septic arthritis of the A-C joint.
      The patient was treated for six weeks with antibiotics successfully. Infection of
      the A-C joint is uncommon, even in conditions such as immunodeficiency, renal
      dialysis and intravenous drug abuse which are associated with unusual joint
      infections, and can be differentiated from shoulder joint infection, by maximal
      tenderness over the A-C joint on examination, and findings of A-C joint widening,
      effusion, and bony erosions on imaging studies.

PMID- 16417194
TI  - Anthropology and psychiatry.
AB  - In this paper anthropology and psychiatry are defined as well as their scientific
      area, their methods and research objectives; the high level of their mutual
      thematic and methodological complementarity has been emphasized. The
      sociocultural factors which are inherent in the area of cultural anthropology can
      affect mental health in a number of ways: by forming a certain personality type
      that is predisposed for a certain type of disorder, by an education model which
      increases the frequency of some disorders, by criticism and sanctions of a
      certain behaviour that is actually desirable from the point of view of mental
      health preservation, by supporting and rewarding a behaviour model that is
      harmful for mental health; by its complexity and, in some of the segments, by
      mutual contradictions they can cause mental disorders; by forming symptoms of
      mental disorders i.e. by a pathoplastic action through which they become an area
      of scientific interest of cultural psychiatry. Anthropology directs psychiatry
      towards creating preventive and therapeutic programs that accept the mutual
      influence and interconnectedness of socio-cultural conditions and the mental
      health status.

PMID- 16417195
TI  - Virilizing adrenal cancer and bail-out nephrectomy.
AB  - We report a rare case of virilizing adrenal cancer with tumorous invasion of the
      left renal vein in which a retroperitoneal adrenalectomy with bail-out
      nephrectomy was performed. A tumor thrombus infiltrated the wall of the left
      adrenal vein and extended into the left renal vein. Initially, a kidney sparing
      procedure with partial tangential excision of the involved renal vein wall was
      performed. After positive vein margins were confirmed with intraoperative
      histology, the indication for nephrectomy was made. To the authors' awareness,
      this is the first report of a virilizing adrenal cancer with a tumor thrombus
      infiltration of the renal vein and surgical tendency for kidney preservation.

PMID- 16417196
TI  - Massacre over civilians during the war in Croatia.
AB  - The 1991-1995 War for independence of Croatia was a cruel armed conflict,
      provoked by the conquering aspirations of the "Yugoslav Federal Army" under
      Serbian command and Serbian terrorists. It took place on the territory of the
      Republic of Croatia and gave rise to a mass destruction of civilian and sacral
      buildings and civilian massacres. Here we present three representative cases as
      an example of the massacre over civilians that happened in the vicinity of
      Vrhovine, in northwestern Croatia. Seven civilians were taken from their homes in
      the village of Dabar, exposed to unprecedented, savage torture and cruel
      execution. Forensic medicine experts revealed that victims were beaten with blunt
      objects, probably the butt end of rifles or high boots, stabbed with sharp
      objects as they were dying, and finally killed by gunshots. Their dead bodies
      were mutilated by cutting auricles and exposed to post-mortem humiliation. Events
      at Vrhovine have all the characteristics of crimes against humanity and
      inapprehensible breaches of the Geneva Convention at the very end of 20th
      century.

PMID- 16417198
TI  - Papers on human evolution published in Collegium Antropologicum from 1977-2004.
AB  - Papers on human evolution published in Collegium Antropologicum in the period
      from 1977 to 2004 are listed in this review.

PMID- 16417197
TI  - Bioarchaeological research in Croatia--a historical review.
AB  - The study of human skeletal remains from archaeological sites gives us the
      opportunity to answer important questions about the lifestyle of past
      populations. The discipline that studies human skeletal remains is known as
      bioarchaeology. This paper provides a historical review of bioarchaeological
      research in Croatia. It is based on the available published material that
      analyzes human skeletal remains from archaeological sites located on the Croatian
      territory covering time span from the Neolithic period to the late Middle Ages.

PMID- 16417199
TI  - Trichinella spiralis and breast carcinoma--a case report.
AB  - Authors report about a patient with recurrent ductal invasive breast carcinoma
      and trichinosis. The patient underwent mastectomy of the left breast with
      evacuation of the axilla because of the cancer. Radiation therapy was received.
      An infestation with Trichinella spiralis was diagnosed two years after The
      patient was treated with mebendazole. A local recurrence of the tumor was found
      on the chest wall six years after the surgery. Tumor excision was performed.
      Histological analysis pointed at a ductal invasive carcinoma with numerous
      parasites of Trichinella spiralis present within both the muscle and the tumor
      tissue. The finding of parasites in the tumor tissue witnesses in favor of
      infestation, and the parasite morphology preserved in the tumor shows at the
      protective effects of the cysts, i.e. preventing parasite necrosis.

PMID- 16417200
TI  - Identification of brucella species and biotypes using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP).
AB  - Brucellosis is a worldwide zoonosis causing reproductive failures in livestock
      and a severe multi-organ disease in humans. The genus Brucella is divided into
      seven species and various biotypes differing in pathogenicity and host
      specificity. Although Brucella spp. represent a highly homogenous group of
      bacteria, RFLPs of selected genes display sufficient polymorphism to distinguish
      Brucella species and biovars. PCR-RFLP analysis shows excellent typeability,
      reproducibility, stability, and epidemiological concordance. Consequently, PCR
      RFLP assays of specific gene loci can serve as tools for diagnostic,
      epidemiological, taxonomic, and evolutionary studies. Various PCR-RFLPs used for
      the identification of Brucella species and biotypes are reviewed.

PMID- 16417201
TI  - Fungal diversity and use in decomposition of environmental pollutants.
AB  - This article presents a critical review of the actual state of fungal activities
      on environmental pollutants, fungal diversity, the use of fungi in the
      degradation of chemical pollutants, enzyme degrading systems and perspectives on
      the use of fungi in bioremediation and unexplored research. The ability of fungi
      to transform or metabolize chemical pollutants has received much attention due to
      environmental persistence and chemical toxicity. The fungal degradation of
      xenobiotics is looked upon as an effective method of removing these pollutants
      from the environment by a process which is currently known as bioremediation.
      This review summarizes information from fundamental works that have revealed that
      a wide variety of fungi are capable of degrading an equally wide range of toxical
      chemical. The capacity of non-ligninolytic and ligninolytic fungi in the
      bioremediation of polycyclic aromatic hydrocarbon (PAHs), benzene-toluene
      ethylbenzene-xylene (BTEX), chlorophenols, polychlorinated biphenyl, munitions
      waste and pesticides have been discussed. Besides this, several extracellular
      enzymes are involved in the metabolism of xenobiotic compounds as well as other
      factors related to these processes.

PMID- 16417202
TI  - Biofouling and biocorrosion in industrial water systems.
AB  - Corrosion associated with microorganisms has been recognized for over 50 years
      and yet the study of microbiologically influenced corrosion (MIC) is relatively
      new. MIC can occur in diverse environments and is not limited to aqueous
      corrosion under submerged conditions, but also takes place in humid atmospheres.
      Biofouling of industrial water systems is the phenomenon whereby surfaces in
      contact with water are colonized by microorganisms, which are ubiquitous in our
      environment. However, the economic implications of biofouling in industrial water
      systems are much greater than many people realize. In a survey conducted by the
      National Association of Corrosion Engineers of the United States ten years ago,
      it was found that many corrosion engineer did not accept the role of bacteria in
      corrosion, and many of then that did, could not recognize and mitigate the
      problem. Biofouling can be described in terms of its effects on processes and
      products such as material degradation (bio-corossion), product contamination,
      mechanical blockages, and impedance of heat transfer. Microorganisms distinguish
      themselves from other industrial water contaminants by their ability to utilize
      available nutrient sources, reproduce, and generate intra- and extracellular
      organic and inorganic substances in water. A sound understanding of the molecular
      and physiological activities of the microorganisms involved is necessary before
      strategies for the long term control of biofouling can be format. Traditional
      water treatment strategies however, have largely failed to address those factors
      that promote biofouling activities and lead to biocorrosion. Some of the major
      developments in recent years have been a redefinition of biofilm architecture and
      the realization that MIC of metals can be best understood as biomineralization.

PMID- 16417203
TI  - Genetic analysis and attribution of microbial forensics evidence.
AB  - Because of the availability of pathogenic microorganisms and the relatively low
      cost of preparing and disseminating bioweapons, there is a continuing threat of
      biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the
      full and robust forensic exploitation and interpretation of microbial evidence
      from acts of bioterrorism or biocrimes. To respond to the need, greater resources
      and efforts are being applied to the burgeoning field of microbial forensics.
      Microbial forensics focuses on the characterization, analysis and interpretation
      of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or
      inadvertent agent release. To enhance attribution capabilities, a major component
      of microbial forensics is the analysis of nucleic acids to associate or eliminate
      putative samples. The degree that attribution can be addressed depends on the
      context of the case, the available knowledge of the genetics, phylogeny, and
      ecology of the target microorganism, and technologies applied. The types of
      genetic markers and features that can impact statistical inferences of microbial
      forensic evidence include: single nucleotide polymorphisms, repetitive sequences,
      insertions and deletions, mobile elements, pathogenicity islands, virulence and
      resistance genes, house keeping genes, structural genes, whole genome sequences,
      asexual and sexual reproduction, horizontal gene transfer, conjugation,
      transduction, lysogeny, gene conversion, recombination, gene duplication,
      rearrangements, and mutational hotspots. Nucleic acid based typing technologies
      include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and
      microarrays.

PMID- 16417211
TI  - Inhibition of pemphigus vulgaris by targeting of the CD40-CD154 co-stimulatory
      pathway: a step toward antigen-specific therapy?
AB  - The signaling of CD40 by its ligand, CD154, between T and B cells is required for
      humoral immune responses. Thus, blockade of this ligand-receptor interaction can
      prevent the development of antibody-mediated autoimmune diseases through
      different mechanisms.

PMID- 16417212
TI  - UVA-irradiated pheomelanin alters the structure of catalase and decreases its
      activity in human skin.
AB  - More than 40 years ago Aronoff showed that catalase structure and activity is
      seriously affected by photo-oxidation of its own substrate, hydrogen peroxide,
      owing to cleavage of its porphyrin active site. Here we support the results of
      Maresca et al. and expand on them by using structural modeling of native catalase
      and its photo-oxidation product, where both methionine and tryptophan residues
      are oxidized, yielding a deactivated enzyme.

PMID- 16417213
TI  - Regulatory T cells.
AB  - Immunologic self-tolerance is critically dependent on the induction but also on
      the downregulation of immune responses. Though ignored and neglected for many
      years, suppressor T cells, now renamed regulatory T cells (Tregs), play an
      important role in the negative regulation of immune responses. Several subsets of
      Tregs have been described. Naturally occurring CD4(+)CD25(+) Tregs are important
      in the prevention of autoimmune diseases. Type 1 Tregs, another subtype of Treg
      that is inducible, exert their suppressive activity primarily via the release of
      IL-10. Detailed knowledge about the phenotype and mode of action of these cells
      will significantly increase our understanding of the pathogenesis of autoimmune
      diseases and will also help to identify new therapeutic strategies.

PMID- 16417214
TI  - Immunosurveillance and immunoregulation by gammadelta T cells.
AB  - Whereas the vast majority of T cells express a T-cell receptor (TCR) composed of
      alphabeta heterodimers, a smaller population expresses a gammadelta TCR. In
      contrast to alphabeta T cells, gammadelta T cells show less TCR diversity, are
      particularly enriched at epithelial surfaces and appear to respond to self
      molecules that signal potential danger or cellular stress. In addition, various
      subsets of gammadelta T cells have shown antitumor and immunoregulatory
      activities. This review considers what has been discovered about the important
      cutaneous functions of gammadelta T cells through the study of mutant mice and
      offers perspectives on the roles of gammadelta T cells in human disease.

PMID- 16417215
TI  - Cytotoxic T cells.
AB  - The immune system is a complex arrangement of cells and molecules that preserve
      the integrity of the organism by elimination of all elements judged dangerous.
      Within the immune system, a humoral and a cellular as well as an innate and an
      adaptive arm can be differentiated. The key players of adaptive cellular immune
      responses are T lymphocytes in general and, for the effector function, cytotoxic
      T lymphocytes (CTLs) in particular. T lymphocytes arise in the bone marrow and
      migrate to the thymus for maturation. During this process, T cells somatically
      rearrange gene segments, eventually leading to the expression of a unique antigen
      binding molecule, the T-cell receptor (TCR). This receptor allows them to monitor
      all cells of the body, ready to destroy any cell posing a threat to the organism.
      Cytotoxicity is exerted directly through the Fas or perforin pathway and/or
      indirectly by the release of cytokines. Obviously, the activity of such a potent
      cell is tightly regulated. Indeed, a predominance of stimulatory over inhibitory
      signals is required for effective immune responses to pathogens, and a
      predominance of inhibitory over stimulatory signals is required for maintenance
      of self-tolerance. Still, several situations occur in which an inappropriate CTL
      response leads to either autoimmune disease or persistence of pathogens.

PMID- 16417216
TI  - Involvement of PPARgamma in oxidative stress-mediated prostaglandin E(2)
      production in SZ95 human sebaceous gland cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is thought to play a
      role in sebaceous gland cell function. We previously demonstrated in human
      epidermoid carcinoma KB cells that UVB irradiation activates PPARgamma via the
      generation of multiple oxidized glycerophosphocholine species with PPARgamma
      ligand activity. UVB-induced cyclooxygenase 2 (COX-2) expression was also shown
      to be PPARgamma-dependent. We therefore reasoned that PPARgamma activation and
      PPARgamma-dependent COX-2 expression may occur as a general consequence of
      oxidative stress. The present studies were designed to examine the effects of the
      oxidant tert-butylhydroperoxide (TBH) on PPARgamma activation and COX-2
      expression in SZ95 sebocytes. We first verified that functional PPARgamma is
      expressed and activated by UVB irradiation in these cells. We next demonstrated
      that TBH increased PPARgamma reporter activity in SZ95 sebocytes. Increased COX-2
      protein, mRNA expression, and prostaglandin E(2) (PGE(2)) production was observed
      after TBH or PPARgamma agonist treatment. The ability of PPARgamma agonists and
      TBH to induce COX-2 expression and PGE(2) production was blocked by pretreatment
      with the specific PPARgamma antagonist GW9662. Finally, TBH and PPARgamma
      agonists failed to elicit a PGE(2) response in SZ95 sebocytes stably expressing a
      dominant-negative PPARgamma. This study illustrates the importance of the
      PPARgamma system in regulating cellular responses to oxidative stress.

PMID- 16417218
TI  - Role of matrix metalloproteinases in HaCaT keratinocytes apoptosis induced by
      loxosceles venom sphingomyelinase D.
AB  - Envenomation by the spider Loxosceles (brown spider) can result in dermonecrosis
      and severe ulceration. We have previously shown that Loxosceles sphingomyelinase
      D (SMaseD), the enzyme responsible for these pathological effects, induced
      expression of matrix metalloproteinase-9 (MMP-9), which is possibly one of the
      main factors involved in the pathogenesis of the cutaneous loxoscelism. The aim
      of this study was to further investigate the molecular mechanisms triggered by
      Loxosceles SMaseD involved in the initiation of the dermonecrotic lesion, using
      HaCaT cultures, a human keratinocyte cell line, as an in vitro model for
      cutaneous loxoscelism. We show here that SMaseD from Loxosceles spider venom
      induces apoptosis in human keratinocytes, which is associated with an increased
      expression of metalloproteinase-2 and -9, and that the use of metalloproteinase
      inhibitors, such as tetracycline, may prevent cell death and potentially may
      prevent tissue destruction after envenomation.

PMID- 16417217
TI  - Regulatory role for Kruppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA
      treated and psoriatic epidermis.
AB  - In this study, we analyze the expression and potential function of the Kruppel
      like zinc-finger protein Gli-similar protein 1 (Glis1) in normal and inflammatory
      skin and in the differentiation of epidermal keratinocytes. Glis1 mRNA is not
      expressed in normal human epidermis, but is significantly induced in psoriatic
      epidermis and in mouse skin upon treatment with the tumor promoter phorbol-12
      myristate-13-acetate (PMA). The expression of Glis1 is restricted to the
      suprabasal layers. These observations suggest that Glis1 expression is associated
      with hyperplastic, inflammatory epidermis. Consistent with these findings, Glis1
      mRNA is not expressed in undifferentiated or differentiated normal human
      epidermal keratinocytes (NHEK) in culture, but is dramatically induced after the
      addition of PMA or interferon gamma. A similar induction of Glis1 mRNA by PMA
      treatment was observed in the immortalized epidermal keratinocyte cell line NHEK
      HPV, whereas PMA did not induce Glis1 in HaCaT cells or in several squamous cell
      carcinoma cell lines. To obtain insight into its function, Glis1 and a C-terminal
      deletion mutant Glis1DeltaC were expressed in NHEK-HPV cells and changes in
      epidermal differentiation and gene expression examined. Microarray analysis
      revealed that Glis1DeltaC promoted PMA-induced epidermal differentiation, as
      indicated by increased expression of many differentiation-specific genes. This,
      in association with its induction in psoriasis, suggests that transcriptional
      factor Glis1 is involved in the regulation of aberrant differentiation observed
      in psoriatic epidermis.

PMID- 16417220
TI  - Major histocompatibility complex class I chain-related gene A polymorphisms and
      extended haplotypes are associated with familial alopecia areata.
AB  - Alopecia areata (AA) is characterized by hair loss in patches and may progress to
      total loss of scalp hair, or total loss of scalp and body hair. The major
      histocompatibility complex (HLA) is associated with susceptibility to AA, as well
      as other autoimmune diseases. In addition to HLA molecules, non-HLA molecules
      including the major histocompatibility complex class I chain-related gene A
      (MICA), a stress-inducible antigen, are also associated with several autoimmune
      diseases. To investigate associations between AA and the HLA loci, two genes and
      eight microsatellite markers spanning the HLA region were genotyped. MICA(*)6 was
      significantly associated with all phenotypes of AA (P=0.0083), whereas MICA(*)5.1
      was significantly associated with patchy AA (P=0.029). Extended haplotype
      analysis shows the significant associations of haplotypes HLA-DQ1-DR6-MICA(*)5.1
      (P=0.004) and HLA-DQB1*0201-DR3-MICA(*)5.1 (P=0.009) with AA. These results
      suggest that MICA is both a potential candidate gene and part of an extended HLA
      haplotype that may contribute to susceptibility to and severity of AA.

PMID- 16417221
TI  - A novel mutation and large size polymorphism affecting the V2 domain of keratin 1
      in an African-American family with severe, diffuse palmoplantar keratoderma of
      the ichthyosis hystrix Curth-Macklin type.
AB  - Keratin gene mutations affecting nonhelical head and tail domains are not usually
      associated with prominent skin blistering and keratin filament clumping. Instead,
      they have been associated with several distinct clinical phenotypes, such as
      epidermolysis bullosa simplex with mottled pigmentation (mutation P25L in the V1
      domain of keratin 5), epidermolysis bullosa simplex with migratory circinate
      erythema (frameshift mutation c1649delG in the V2 domain of keratin 5), striate
      palmoplantar keratoderma (PPK), and ichthyosis hystrix Curth-Macklin (different
      frameshift mutations in the V2 domain of keratin 1 (K1)). We have studied a
      family with severe, diffuse, nonepidermolytic PPK and verrucous hyperkeratotic
      plaques over the joints and in flexures and identified a new KRT1 gene mutation
      that is predicted to completely alter the K1 tail domain. In addition, a new K1
      size polymorphism has been detected, which is especially prevalent among the
      African-American population. These results further emphasize the functional
      importance of the nonhelical tail domain in keratin molecules despite the obvious
      variability in the number of glycine loop motifs and underscore the broad
      phenotypic spectrum of disorders due to dominant keratin tail mutations.

PMID- 16417219
TI  - The requirement for perp in postnatal viability and epithelial integrity reflects
      an intrinsic role in stratified epithelia.
AB  - Mice lacking the desmosome protein Perp exhibit blistering in their stratified
      epithelia and display postnatal lethality. However, it is unclear if these
      phenotypes are strictly related to Perp function in stratified epithelia, as Perp
      expression is not restricted to these tissues during embryogenesis, and certain
      desmosomal blistering diseases such as pemphigus vulgaris and pemphigus foliaceus
      have non-cell-intrinsic bases. Furthermore, we show here that Perp is expressed
      in the heart, raising the possibility that defects in heart function could
      account for lethality in the Perp-deficient mice. To determine conclusively if
      Perp function in stratified epithelia is crucial for postnatal survival and
      epithelial adhesion, we specifically ablated Perp in stratified epithelia by
      breeding conditional Perp knockout mice to keratin 5 (K5)-Cre transgenic mice. We
      found that the majority of mice lacking Perp in stratified epithelia die within
      10 days after birth, accompanied by blistering and hyperproliferation in the
      epithelia, similar to the constitutive Perp null mice. Together, these findings
      indicate that Perp's requirement for both viability and epithelial integrity
      reflects a role in the stratified epithelial compartment.

PMID- 16417222
TI  - Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak
      syndrome type 1 and 3 mutations in Puerto Rico.
AB  - Hermansky-Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of
      autosomal recessive disorders characterized by oculocutaneous albinism (OCA),
      bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico
      (PR), particularly in the northwest part of the island, with a frequency of
      approximately 1:1,800. Two HPS genes and mutations have been identified in PR, a
      16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto
      Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR)
      (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto
      Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We
      found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D
      mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto
      Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR
      (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most
      frequent in central PR (1:32; 3.1%). Our findings provide insights into the
      genetics of albinism and HPS in PR, and provide the basis for genetic screening
      for these disorders in this minority population.

PMID- 16417223
TI  - Bullous allergic hypersensitivity to bed bug bites mediated by IgE against
      salivary nitrophorin.
AB  - In Central Europe, bites from the common bed bug (Cimex lectularius) are nowadays
      rather uncommon. Nevertheless, infestations are sometimes observed in old
      framehouses and by immigration due to international travel and migration. The
      clinical picture of bug bites substantially varies between individuals, depending
      upon previous exposure and the degree of an immune response. The host immune
      response and potential protein antigens present in the saliva of C. lectularius
      or specific antibodies have not been characterized thus far. We describe a
      patient with bullous bite reactions after sequential contact with C. lectularius
      over a period of 1 year. In skin tests, we observed immediate reactions to the
      salivary gland solution of C. lectularius, which were followed by a pronounced
      partially blistering late-phase response. Immunoblot analysis of the patient's
      serum with salivary gland extracts and recombinant C. lectularius saliva proteins
      revealed specific IgE antibodies against the 32 kDa C. lectularius nitrophorin,
      but not to 37 kDa C. lectularius apyrase. Our data demonstrate that bullous
      cimicosis may be the late-phase response of an allergic IgE-mediated
      hypersensitivity to C. lectularius nitrophorin.

PMID- 16417224
TI  - Antigen-specific peripheral tolerance induced by topical application of NF-kappaB
      decoy oligodeoxynucleotide.
AB  - Activation and maturation of dendritic cells (DC) are crucial for the
      establishment of delayed-type hypersensitivity (DTH). However, antigen
      presentation by immature DC (iDC) might lead to antigen-specific peripheral
      tolerance. NF-kappaB plays significant roles in upregulation of co-stimulatory
      molecules and cytokines in DC and therefore we investigated whether NF-kappaB
      decoy oligodeoxynucleotide (ODN) might induce tolerance to DTH. NF-kappaB decoy
      ODN suppressed ovalbumin (OVA)-induced DTH responses not only in naive but also
      in presensitized mice. The suppressive effect was found to be antigen-specific.
      NF-kappaB decoy ODN-induced tolerance involved CD4(+)CD25(+) regulatory T cells
      (Treg), because in vivo depletion of CD25(+) T cells abrogated the tolerance,
      whereas adoptive transfer of such T cell population from tolerant mice induced
      tolerance. Furthermore, the induction of Treg was related to insufficient
      migration and/or maturation of DC, because a sizable DC population still remained
      in peripheral tissue even after exposure to exogenous antigen in NF-kappaB decoy
      ODN-treated mice. Even if they migrated into lymph nodes, they showed
      insufficient upregulation of co-stimulatory molecules and impaired antigen
      specific activation of T cells. Topical application of NF-kappaB decoy ODN might
      thus be a new approach to induce antigen-specific peripheral tolerance.

PMID- 16417225
TI  - Tolerance induction by the blockade of CD40/CD154 interaction in pemphigus
      vulgaris mouse model.
AB  - Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by IgG
      autoantibodies against desmoglein 3 (Dsg3). We have recently developed an active
      disease mouse model for PV by adoptive transfer of splenocytes from Dsg3(-/-)
      mice. The purpose of this study was to determine the role of CD40/CD154
      interaction in the pathogenic antibody production and development of the disease
      in PV model mice. When anti-CD154 monoclonal antibody (mAb) was administered to
      recipient mice prior to adoptive transfer, anti-CD154 mAb almost completely
      blocked the anti-Dsg3 IgG production and prevented blister formation. The
      blockade of CD40/CD154 interaction induced tolerance against Dsg3 as the
      suppression of antibody production was observed through day 70, and it was
      maintained even after challenge by immunization with recombinant mouse Dsg3 or by
      adoptive transfer of immunized Dsg3(-/-) splenocytes. Furthermore, the tolerance
      to Dsg3 was transferable because cotransfer of splenocytes from anti-CD154 mAb
      treated mice and naive Dsg3(-/-) splenocytes significantly suppressed anti-Dsg3
      IgG production in recipient mice. In contrast, when anti-CD154 mAb was injected
      after the mice had developed the PV phenotype, no significant suppression of the
      production of anti-Dsg3 IgG was observed. These findings indicate that the
      CD40/CD154 interaction is essential for the induction of pathogenic anti-Dsg3 IgG
      antibodies and that antigen-specific immune-regulatory cells induced by anti
      CD154 mAb would hold a therapeutic option for autoimmune diseases.

PMID- 16417226
TI  - Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell
      like dendritic cells from M-CSF-conditioned precursors.
AB  - GM-CSF and transforming growth factor beta (TGFbeta ) are required for the
      generation of Langerhans cells (LC), members of the dendritic cell (DC) family.
      Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation
      from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC
      precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and
      readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin,
      CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck
      granules. TNFalpha and IL-4, added separately or together, have an inhibitory
      effect on LC differentiation. Cells differentiated in the presence of IL-4 and
      TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC
      precursors retain the capacity to efficiently undergo a differentiation program,
      giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.

PMID- 16417227
TI  - Pseudomonas aeruginosa- and IL-1beta-mediated induction of human beta-defensin-2
      in keratinocytes is controlled by NF-kappaB and AP-1.
AB  - Human beta-defensin-2 (hBD-2) is an inducible epithelial peptide antibiotic
      involved in cutaneous defense. Expression of hBD-2 in keratinocytes is strongly
      induced by IL-1beta and culture supernatants of Pseudomonas aeruginosa (PA). The
      use of an IL-1 receptor antagonist revealed that PA-mediated induction of hBD-2
      is not dependent on IL-1. Luciferase gene reporter experiments, demonstrated that
      a 2,338 bp promoter fragment of hBD-2 containing three putative NF-kappaB as well
      as one activator protein-1 (AP-1) binding site was strongly activated by IL-1beta
      and PA. Mutation of all NF-kappaB binding sites together with mutation of the AP
      1 binding site completely abolished hBD-2 promoter activation by IL-1beta and PA.
      Treatment with the NF-kappaB inhibitor Helenalin as well as with the c-Jun N
      terminal kinase (JNK) inhibitor SP600125 and the p38 mitogen-activated protein
      kinase inhibitor SB 202190 blocked hBD-2 induction by IL-1beta and PA. PD 98059,
      a selective inhibitor of extracellular signal-regulated kinase 1/2 demonstrated
      no significant influence. Transcription factor ELISAs indicated that the NF
      kappaB heterodimer p50-p65 binds to all three NF-kappaB sites in the hBD-2
      promoter upon stimulation of primary keratinocytes with IL-1beta and PA. We
      conclude that the activation of NF-kappaB (p50-p65) and AP-1 are crucial events
      for induction of hBD-2 in keratinocytes upon IL-1beta and PA stimulation.

PMID- 16417228
TI  - Local expression of indoleamine 2,3-dioxygenase protects engraftment of
      xenogeneic skin substitute.
AB  - The expression of indoleamine 2,3-dioxygenase (IDO), which metabolizes
      tryptophan, an essential amino acid, into kynurenine, has been identified as
      having a key role in the prevention of the immune rejection of the semi
      allogeneic fetus during pregnancy. We have previously demonstrated that IDO
      expressed in fibroblasts causes bystander CD4(+) T cell damage as well as THP-1
      cell damage by apoptosis. As T cells are primarily responsible for graft
      rejection, here, we asked the question of whether engraftment of IDO-expressing
      xenogeneic fibroblasts populated in a collagen matrix can be immuno-protected in
      an animal model. The results show a significant reduction in the number of
      infiltrated CD3(+) T lymphocytes on days 14 and 28 post-transplantation in the
      wounds receiving IDO-expressing fibroblasts relative to controls. IDO-expressing
      human fibroblasts embedded in bovine collagen on wounds in a rat model
      accelerates wound healing by promoting neovascularization during the early stages
      and providing protection of the xenograft fibroblasts. Using a co-culture system,
      we further confirm that IDO can induce angiogenesis through the depletion of
      tryptophan. These findings suggest that IDO may have an application in promoting
      the engraftment of skin substitutes and other transplanted organs.

PMID- 16417229
TI  - Dysregulation of TAp63 mRNA and protein levels in psoriasis.
AB  - Psoriasis is a chronic and excessive inflammation of the skin and is currently
      incurable. The cause of psoriasis remains poorly understood and a central and
      cooperative role for keratinocytes and T-cells in triggering the disease is
      highlighted. The p63 gene encodes six different proteins with homology to the
      tumor suppressor protein p53 that are crucial for normal development of
      ectodermally derived structures such as skin and oral mucosa. In this study, we
      have analyzed levels of the different p63 isoforms using quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 15
      patients diagnosed with psoriasis. Quantitative RT-PCR results showed
      downregulation of the full-length TAp63 in psoriatic lesions compared to both
      clinically normal skin from patients (P<0.001) and matched healthy controls
      (P<0.001); however, p63 protein levels detected by immunohistochemistry were
      similar. All psoriasis lesions also had detectable levels of activated Stat3, a
      protein indicated in development of the disease, whereas control tissue lacked
      this protein. The present data show a different regulation of TAp63 in psoriasis,
      where the discrepancy between mRNA levels and protein expression indicates a post
      transcriptional regulation analogous to that seen in p53.

PMID- 16417230
TI  - Melanoma, a tumor based on a mutant stem cell?
AB  - Stem cells play a critical role in normal tissue maintenance, and mutations in
      these stem cells may give rise to cancer. We hypothesize that melanoma develops
      from a mutated stem cell and therefore residual stem cell characteristics should
      be able to be identified in melanoma cell lines. We studied three metastatic
      melanoma cell lines that exhibited multiple morphologic forms in culture and
      demonstrated the capacity to pigment. We used the ability to efflux Hoechst 33342
      dye, a technique known to enrich for stem cells in many tissues, to segregate
      cell populations. The cells with the greatest ability to efflux the dye were (1)
      small in size, (2) had the capacity to give rise to larger cell forms, and (3)
      had the greatest ability to expand in culture. The small cells were found to have
      a decreased proliferative rate and were less melanized. Large dendritic cells
      that appeared to be nonproliferative were identified in cultures. Treatment with
      cytosine beta-D-arabinofuranoside hydrochloride (Ara-C) expanded the large cell
      population but the residual proliferative capacity, both in vitro and in vivo,
      remained concentrated in the smaller cell fraction. Antigenic staining patterns
      were variable and heterogeneous. Nestin (a neural stem cell marker) and gp100
      (premelanosomal marker) favored the smaller cell population, while nerve growth
      factor receptor often labeled larger cells. Morphologic and antigenic
      heterogeneity remained intact after clonal purification. These findings are
      consistent with the behavior expected for a tumor based on stem cell biology;
      this finding has diagnostic and therapeutic implications for melanocytic
      neoplasias.

PMID- 16417231
TI  - Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma.
AB  - Frequent somatic mutation of v-raf murine sarcoma viral oncogene homolog B
      (BRAF), a downstream effector of the rat sarcoma oncogene (RAS) signaling
      pathway, is described in melanoma and other tumors. Our analysis of melanoma cell
      lines suggests that activating mutations in BRAF can occur simultaneously with
      inactivation of phosphatase and tensin homolog (PTEN), but neuroblastoma RAS
      (NRAS) mutations are not coincident. We determined the concurrent prevalence of
      mutations in BRAF and NRAS, and alteration of PTEN expression in 69 primary
      cutaneous melanomas. BRAF mutations were seen in 57% of cases. NRAS was mutated
      in 17% of samples, exclusively in exon 2. Two cases showed concurrent BRAF and
      NRAS mutations. Using immunohistochemistry, PTEN protein expression was lost or
      greatly reduced in 19% of tumors. Seven tumors with reduced PTEN yielded DNA
      amenable to sequencing, and three also showed mutation in BRAF but none in NRAS.
      In all, 11 (85%) of 13 tumors showing reduced PTEN expression were greater than
      3.5 mm thick, and the association of increasing Breslow thickness and loss or
      reduction of PTEN expression was statistically significant (P<0.0001). Mutations
      in NRAS were not coincident with reduced PTEN expression, and the concurrent
      mutation of NRAS and BRAF was rare.

PMID- 16417232
TI  - Lack of association between BRAF mutation and MAPK ERK activation in melanocytic
      nevi.
AB  - The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase
      signaling pathway can be activated through mutations of V-RAF murine sarcoma
      viral oncogene homolog B1 (BRAF) oncogene, frequently found in melanoma (60%),
      common nevi (CN) (73-82%), and atypical nevi (AN) (52-80%). MAPK activation has
      been reported between 0 and 22% in nevi, and 86% of primary melanoma, without any
      knowledge of BRAF mutational status. We studied the correlation of MAPK
      activation status, BRAF mutation, and B-Raf expression in CN, AN, and melanoma.
      Using immunohistochemistry, phosphorylated (active) MAPK and B-Raf expression was
      studied in 24 CN, 21 AN, and 26 primary cutaneous melanomas (PM). BRAF mutations
      at codon 600 were assessed by PCR-RFLP. Active MAPK was detected in 29% of CN,
      48% of AN, and 85% of PM. BRAF mutation was found in 67% of CN, 62% of AN, and
      58% of PM. In all, 23% of CN, 54% of AN, and 93% of PM with BRAF mutation have
      activated MAPK. All lesions expressed B-Raf. BRAF mutation does not seem to be
      sufficient to produce MAPK activation in melanocytic nevi, and it is suggested
      that other events are needed to induce MAPK activation, that is, B-Raf
      overexpression, inhibition of MAPK phosphatases, or suppression of RAF kinase
      inhibitors.

PMID- 16417233
TI  - Promoter hypermethylation of the O(6)-methylguanine DNA methyltransferase gene
      and microsatellite instability in metastatic melanoma.
AB  - Tumor spread to distant organs is the most serious consequence of melanoma, as
      only 10-20% of stage IV patients respond to current chemotherapies. Tumor
      sensitivity to alkylating agents is affected by the activity of cellular DNA
      repair proteins, such as O(6)-methylguanine DNA methyltransferase (MGMT) and the
      DNA mismatch repair proteins. Chemosensitivity may be enhanced by reduced MGMT
      activity, but the frequency of MGMT promoter silencing through hypermethylation
      is unknown in distant melanoma metastases. The frequency and significance of
      microsatellite instability (MSI) in metastatic melanoma is also unclear, and it
      has been suggested that MSI frequency increases during the metastatic process. We
      undertook an analysis of 84 melanoma metastases from 47 patients. MGMT
      methylation was detected using methylation-specific PCR in 26 of the 84
      metastases (31%), but there was discordance between individual metastases from
      the same patient. Therefore, as a result of this variation, MGMT methylation may
      have only limited value as a predictor of chemosensitivity. High MSI involving
      mononucleotide repeat markers was not found. Low MSI was detected in five of 50
      metastases (10%) and only one of the five metastases also had MGMT methylation.
      These results demonstrate that in contrast to some previous reports, these tumors
      have a low frequency of MSI.

PMID- 16417234
TI  - Dimerization of the human melanocortin 1 receptor: functional consequences and
      dominant-negative effects.
AB  - The melanocortin 1 receptor (MC1R), a G(S)-protein-coupled receptor (GPCR), is a
      key regulator of proliferation and differentiation of epidermal melanocytes, and
      a determinant of human skin phototype and cancer risk. Homodimerization has been
      demonstrated for several GPCRs, but little information is available for MC1R. SDS
      PAGE analysis of melanoma cells and heterologous cells expressing epitope-tagged
      MC1R revealed dimeric and oligomeric species in detergent-solubilized extracts,
      confirmed by co-immunoprecipitation of differentially tagged MC1R forms.
      Dimerization occurs early during MC1R biosynthesis, and is seen for mutants
      displaying intracellular retention. These mutants exerted dominant-negative
      effects on wild-type (WT) MC1R. Conversely, partial functional trans
      complementation of selected loss-of-function mutants was observed. WT-MC1R lacks
      cooperativity in agonist binding, yet coexpression of WT and a C-terminal
      deletion mutant yielded a form of different pharmacological properties. The
      natural diminished function alleles R151C, R160W, and D294H, associated with red
      hair, displayed dimerization and heterodimerization with WT. Coexpression of WT
      and R151C or R160W reduced the density of binding sites on the plasma membrane of
      transfected cells, whereas D294H mediated a dominant-negative effect on
      functional coupling to adenylyl cyclase. Therefore, subtle changes of functional
      properties may be associated with different MC1R haplotypes, contributing to the
      complexity of skin phenotype.

PMID- 16417235
TI  - UVA-induced modification of catalase charge properties in the epidermis is
      correlated with the skin phototype.
AB  - The harmful effects of UVA radiation (320-400 nm) on the skin have been related
      to the generation of reactive oxygen species. Pheomelanin, the pigment
      characteristic of fair-skinned individuals, amplifies these effects. In vitro, in
      the presence of photosensitizing agents, UVA light produces singlet oxygen, which
      reacts with several targets. We have investigated a possible correlation between
      melanin-type and the antioxidant defense system after UV, focusing on the
      activities of superoxide dismutase and catalase, which correlated with the
      phototype of epidermal reconstructs. UVA was more effective than UVB in damaging
      these enzymatic activities, especially catalase. Furthermore, UVA irradiation
      induced a free-radical-mediated damage in the cells, leading to an oxidation of
      cell proteins. On catalase, synthetic pheomelanin amplified this effect on
      specific targets, such as residues of tryptophan and methionine. UVA irradiation
      of low phototype reconstructed epidermis and of U937 through synthetic
      pheomelanin induced a modification in the electrophoretic properties of native
      catalase, which was counteracted by histidine, a quencher of singlet oxygen.
      These results demonstrate that pheomelanin could act as a photosensitizing agent,
      following UVA irradiation, inducing charge modifications of native catalase, by a
      mechanism involving singlet oxygen or its downstream products.

PMID- 16417236
TI  - Photoimmunoprotection by UVA (320-400 nm) radiation is determined by UVA dose and
      is associated with cutaneous cyclic guanosine monophosphate.
AB  - The immunomodulating properties of UVA radiation remain controversial. Here, we
      demonstrate in female inbred Skh:hr-1 mice that single subinflammatory UVA
      exposures between 1.61 and 580.5 kJ/m(2) are not immunosuppressive. Furthermore,
      UVA exposures between 16.13 and 580.5 kJ/m(2) provided dose-related
      immunoprotection against UVB-induced immunosuppression. Higher UVA exposures
      (870.8-1,161 kJ/m(2)) became inflammatory and immunosuppressive alone, and lost
      the photoimmunoprotective capacity. We previously reported that UVA
      photoimmunoprotection depends on the induction of cutaneous heme oxygenase-1,
      particularly its enzymatic product, carbon monoxide (CO). CO was suggested to
      activate cutaneous guanylyl cyclase (GC), as the specific GC inhibitor, 1H
      (1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), abrogated CO
      photoimmunoprotection in the mouse. This study shows that cutaneous cyclic
      guanosine monophosphate (cGMP) concentration increased only following
      immunoprotective UVA doses, or immunoprotective topical CO treatment, and cGMP
      production was inhibited by ODQ. Conversely, cGMP concentration was increased by
      inhibition of its degradative phosphodiesterase (PDE) with topical sildenafil.
      The PDE-5 isoform was identified in normal mouse skin. Subsequently, a moderate
      concentration of sildenafil was shown to simulate the effect of UVA in protecting
      against photoimmunosuppression by solar-simulated UV radiation or its mediator
      cis-urocanic acid. Thus, cutaneous cGMP, controlled by its synthesis via CO
      activated GC and its degradation by PDE-5, is strongly associated with UVA
      photoimmunoprotection.

PMID- 16417237
TI  - Isoflavonoid photoprotection in mouse and human skin is dependent on
      metallothionein.
AB  - Previous studies report that selected topical isoflavonoids are immunoprotective
      in both mice and humans, when applied following UV irradiation. Isoflavonoids
      have documented antioxidant activity, but their mechanism of immunomodulation
      remains unclear. This study examines whether photoimmunoprotection by the
      isoflavonoids might result from their interaction with one cutaneous antioxidant
      known to modulate UV photodamage, metallothionein (MT). In mice bearing a null
      mutation for MT-I and -II, we found that immunoprotection by the isoflavonoid
      4',7-dihydroxyisoflavane (equol) against solar-simulated UV radiation (SSUV) or
      exogenous cis-urocanic acid was abrogated. Topical equol did not activate MT
      expression in normal mouse skin, but markedly enhanced the increase in MT
      expression in murine epidermis following SSUV irradiation. Normal human skin,
      unlike murine, expressed MT in the basal epidermis. Following SSUV irradiation,
      topical application of the related synthetic isoflavonoid NV-07alpha to human
      skin also markedly enhanced epidermal MT expression. The NV-07alpha has been
      reported previously to protect humans against the UV suppression of Mantoux
      reactions. Thus, epidermal MT expression appears to protect against
      photoimmunosuppression in both human and mouse skin. We speculate that equol and
      its related derivative NV-07alpha may activate the MT gene synergistically with
      SSUV, to produce the enhanced immunoprotective effect.

PMID- 16417238
TI  - Importance of the EP(1) receptor in cutaneous UVB-induced inflammation and tumor
      development.
AB  - Chronic exposure to UV light, the primary cause of skin cancer, results in the
      induction of high levels of cyclooxygenase-2 (COX-2) expression in the skin. The
      involvement of COX-2 in the carcinogenesis process is mediated by its enzymatic
      product, prostaglandin E(2) (PGE(2)). PGE(2) has been shown to have a variety of
      activities that can contribute to tumor development and growth. The effects of
      PGE(2) on different cell types are mediated by four E prostanoid (EP) receptors,
      EP(1)-EP(4). While recent studies have demonstrated the importance of EP(1) in
      the development of colon and breast cancer, the extent of EP(1) involvement in
      the cutaneous photocarcinogenesis process is unknown. This study found that
      topical treatment with celecoxib or the specific EP(1) antagonist ONO-8713
      decreased acute UVB-induced inflammation in the skin and significantly reduced
      the number of tumors per mouse following 25 weeks of UVB exposure and topical
      treatment. This study suggests that drugs designed to block EP(1) may have the
      potential to be used as anti-inflammatory and/or chemopreventive agents that
      reduce the risk of skin cancer development.

PMID- 16417240
TI  - Characterization of a "blanch-blush" mechano-response in palmar skin.
AB  - Palmar finger skin reacts to extension under mechanical load -- blanching over
      proximal (intercrease skin, ICS) and middle phalanges, while blushing in crease
      skin (CS), which we have called the Blanch-Blush Reaction (BBR). The idea that
      the BBR is a result of surface capillary blood flow changes that relate to
      predictable deformation of aligned collagen matrices under applied uniaxial loads
      was tested. Nondestructive techniques, digital image analysis (DIA), laser
      Doppler scanning, and elastic scatter spectroscopy (ESS) were used to measure
      color and blood flow changes in healthy fingers when at rest and extended. Skin
      strain increased directly with applied load and DIA identified blanching (loss of
      redness) in the ICS, reflected by a decrease in hemoglobin (by ESS). Laser
      Doppler flowmetry identified an increase in blood flow in the CS zone on
      extension, with a minor increase in blood flow in the ICS zone, apparently due to
      diversion of flow to deeper vessels, when monitored by this technique. These
      changes correlated with the BBR, owing to altered capillary flow in the ICS and
      CS. The histology of orientation of collagen fibers and vessels in the two zones
      was consistent with this mechanism. This study demonstrates the interdependence
      between matrix orientation, applied load, and flow. It represents an elegant
      demonstration of collagenous tissue function through an everyday tissue reaction,
      which has not been described previously.

PMID- 16417239
TI  - Increased expression of CTLA-4 in malignant T-cells from patients with mycosis
      fungoides -- cutaneous T cell lymphoma.
AB  - Mycosis fungoides (MF) is a low-grade lymphoma of cluster of differentiation
      (CD)4+, CD45RO+, cutaneous leukocyte antigen (CLA)+ T cells that homes to the
      skin. To understand the functional abnormalities in this disease, we study the
      regulation of cytotoxic T-lymphocyte antigen (CTLA)-4 in peripheral blood
      mononuclear cells (PBMCs) from patients with MF. CTLA-4 is a costimulatory
      molecule for T cells that functions in immunoregulation. Unlike the expression of
      CD28, which is expressed constitutively on T cells, CTLA-4 expression is highly
      regulated. In the analysis of PBMCs in MF, we found that CTLA-4 is stimulated by
      phorbol myristate acetate/A23187 to a greater level when compared to normals.
      This defect was seen in the dominant clones of T cells. The increased CTLA-4
      expression was significant between normal and MF, with a correlation between
      higher expression of CTLA-4 and a higher grade of MF. In a patient whose disease
      progressed, the CTLA-4 level increased. The abnormal level of CTLA-4 was
      confirmed at both the transcription and translation levels. Although MF is
      associated with a Th2 bias, Th1 cytokines IL-2 and IFN-gamma enhanced CTLA-4
      expression, while IL-4 did not. These findings reveal an abnormal regulation of
      CTLA-4 expression in MF and show that PBMCs from patients with MF have properties
      that are divergent from those of normal T cells.

PMID- 16417241
TI  - Circulating CLA(+) T cells from acute and chronic psoriasis patients manifest a
      different activation state and correlation with disease severity and extension.

PMID- 16417242
TI  - Aminoglycosides as potential pharmacogenetic agents in the treatment of Hailey
      Hailey disease.

PMID- 16417243
TI  - Protein structural analysis of BP180 mutant isoforms linked to non-Herlitz
      junctional epidermolysis bullosa.

PMID- 16417245
TI  - Synthesis and characterization of a head-tail type polycation block copolymer as
      a nonviral gene vector.
AB  - A head-tail type polycation block copolymer, which is composed of the
      polyamidoamine (PAMAM) dendron and poly(L-lysine) (PLL) blocks, was newly
      designed as a nonviral gene vector in this study. This block copolymer (PAMAM
      dendron-PLL) was successfully synthesized in two steps: the synthesis of the
      PAMAM dendron block and the polymerization of the PLL block from the PAMAM
      dendron block. PAMAM dendron and PLL blocks in block copolymer showed independent
      deprotonation behavior, and their pK(a) were determined to be 6.8 and 9.0,
      respectively. The complexation with pDNA was evaluated by gel retardation assay
      and dye exclusion assay, and both assays indicated that pDNA was selectively
      complexed with PLL block of block copolymer. Also, the PAMAM dendron-PLL
      poplyplexes showed 10(2) fold higher transfection efficiency to HeLa cells as
      that for PLL polyplexes. This might be due to the buffering effect of the PAMAM
      dendron block. This block copolymer could produce a function share in each block,
      i.e., tail block complexed with pDNA and head block showed a buffering effect.
      This molecular design of the head-tail type block copolymer might provide a new
      approach for realizing in vivo gene therapy.

PMID- 16417246
TI  - Water-soluble dendrigrafts bearing saccharidic moieties: elaboration and
      application to enzyme linked OligoSorbent Assay (ELOSA) diagnostic tests.
AB  - The synthesis of a series of water-soluble galactopyranose-functionalized
      polystyrene-polyvinyl ether dendrigrafts and their characterization (in solution
      and thin solid deposits) have been achieved. The presence of external
      galactopyranose groups on dendritic polymers has been exploited to prepare
      dendrigraft-oligonucleotide conjugates using a simple one-step coupling procedure
      with amino-ended oligonucleotides (ODNs). Several parameters such as the
      peripherical density of hydrophilic branches, the polymerization degree of
      polystyrene or poly(hydroxyethyl vinyl ether) blocks, and the number of
      galactopyranose groups were tuned. A capture test with short labeled
      complementary ODNs (25 bases) confirmed the presence of covalently bound ODNs on
      various kinds of dendrigrafts. The ability of the dendritic polymers to enhance
      the sensitivity of enzyme-linked oligosorbent assay (ELOSA) diagnostic tests
      (detection of hepatitis B virus, DNA target of 2400 bases) was then evaluated,
      especially the influence of the macromolecular architecture and the impact of the
      structural parameters. The dendrigraft-ODN conjugate with the lower saccharide
      external density was found to lead to a very significant amplification of the
      fluorescence signal, corresponding to a limit of sensitivity of 10(9) DNA copies
      per milliliter (instead of 10(11) DNA copies per milliliter without using
      dendrigrafts). Conversely, the dendrigrafts exhibiting a very high number of
      branches and galactopyranose groups at their periphery were not able to induce a
      better sensitivity due to steric hindrance generated by the peripheral congestion
      on these polymers.

PMID- 16417247
TI  - Unilamellar liposomes with enhanced boron content.
AB  - A new type of boron-rich, DSPC-free, unilamellar liposomes was formed using the
      novel dual-chain, ionic, nido-carborane lipid, K[nido-7-(C16H33OCH2)2CHOCH2-7,8
      C2B9H11] (DAC-16), and cholesterol for encapsulation of an aqueous buffer core.
      Since DSPC was not necessary for the formation of stable DAC-16 liposomes, the
      boron concentration of these vesicles was increased dramatically to approximately
      8.8 wt % in the dry lipid; these liposomes had a high bilayer boron incorporation
      efficiency of 98%. DSPC-free liposomes exhibited a size distribution pattern of
      40-60 nm, which was in the range normally associated with selective tumor uptake.
      This size distribution was maintained throughout storage at room temperature for
      several months. Additionally, optimized liposome formulations incorporating DAC
      16, DSPC, and cholesterol were identified having stable size distribution
      patterns after storage for more than two months at a variety of temperatures.
      Although animal studies indicate that DAC-16 liposomes are toxic, this new ionic
      nido-carborane lipid allows the formation of liposomes of high boron content for
      in vitro applications that require the delivery of large amounts of boron.

PMID- 16417248
TI  - Generic bioaffinity silicone surfaces.
AB  - Synthetic polymer surfaces require surface modification to improve
      biocompatibility. A generic route to biocompatible silicone elastomers is
      described involving high yield surface functionalization of standard silicones
      with hydrosilanes, hydrosilylation using asymmetric, allyl-, NSC-terminated PEO
      of narrow molecular weight, and covalent modification in one step with amine
      containing biological molecules including oligopeptides (YIGSR, RGDS), proteins
      (EGF, albumin, fibrinogen, mucin), and glycosaminoglycans (heparin). Efficient,
      high-density binding (e.g., 0.2 EGF molecules/nm2) was demonstrated using
      radiolabeling studies. The resulting surfaces were demonstrated to be
      biocompatible by further reaction with biomolecules, for example, thrombosis
      suppression on surfaces modified by heparin + ATIII, and the formation of
      confluent corneal epithelial cell layers on EGF, RGDS, or YIGSR surfaces.

PMID- 16417249
TI  - Synthesis and evaluation of novel dendrimers with a hydrophilic interior as
      nanocarriers for drug delivery.
AB  - Novel polyester-co-polyether dendrimers consisting of a hydrophilic core were
      synthesized by a combination of convergent and divergent syntheses. The core was
      synthesized from biocompatible moieties, butanetetracarboxylic acid and aspartic
      acid, and the dendrons from PEO (poly(ethylene oxide)), dihydroxybenzoic acid or
      gallic acid, and PEG monomethacrylate. The dendrimers, Den-1-(G 2) (second
      generation dendrimer-1) and Den-2-(G 2) (second generation dendrimer-2)
      consisting of 16 and 24 allyl surface groups, respectively, were obtained by
      coupling the dendrons to the core. The dendrimer (Den-1-(G 2)-OH) with hydroxyl
      groups at the surface was synthesized by oxidation of the allyl functional groups
      of Den-1-(G 2), which was divergently coupled to the dendrons to obtain the third
      generation dendrimer Den-1-(G 3) consisting of 32 surface groups. The
      modifications in surface groups and generation of dendrimers were shown to
      influence the shape of dendrimers in the AFM studies. The aggregation as well as
      self-assembly of dendrimers was observed at high concentration in water by light
      scattering studies; however, it was reduced on dilution and in the presence of
      sodium chloride. Dendrimers demonstrated good ability to encapsulate the guest
      molecule, with loading of 15.80 and 6.47% w/w for rhodamine and beta-carotene,
      respectively. UV spectroscopy proved the absence of any pi-pi complexation
      between the dendrimer and encapsulated compounds. (1)H NMR and FTIR studies
      showed that the physical entrapment and/or hydrogen bonding by PEO in the
      interior and branch of the dendrimer are the mechanisms of encapsulation. The
      release of the encapsulated compounds was found to be slow and sustained,
      suggesting that these dendrimers can serve as potential drug delivery vehicles.

PMID- 16417250
TI  - Synthesis and characterization of HE-24.8: a polymeric contrast agent for
      magnetic resonance angiography.
AB  - The physical and biological properties of a water-soluble polymeric contrast
      agent based on a complex of N-(2-hydroxypropyl)methacrylamide copolymer with
      gadolinium (HE-24.8) were investigated, and its potential for experimental
      magnetic resonance (MR) angiography was assessed. Relaxivities of Gd-DTPA-BMA, Gd
      DTPA-HSA (human serum albumin), and HE-24.8 were determined at 1.5 T. Thermic
      stability and biocompatibility of HE-24.8 were assessed in vitro and by analyzing
      kinetics and organ distribution in rats for up to 2 weeks. For comparison, HE
      24.8- and Gd-DTPA-HSA-enhanced micro-MR angiographies of brain, chest, and
      subcutaneous tumors in rats were performed. T1 relaxivity of HE-24.8 (21.3 +/-
      1.1 mM(-1) s(-1)) was 5-fold higher than that of Gd-DTPA-BMA (4.1 +/- 0.1 mM(-1)
      s(-1)) and twice as high as that of Gd-DTPA-HSA (12.4 +/- 0.2 mM(-1) s(-1)).
      Varying the molecular weight of the polymer (15-46 kDa) did not significantly
      change the T1 relaxivity. In rats, 20 and 10% of the injected dose of HE-24.8 was
      detected at 24 and 168 h postinjection, respectively. Upon a relatively rapid
      initial renal clearance, no specific retention in any organ was noted, with some
      exception for the reticulo-endothelial system. No measurable release of
      gadolinium from the polymer-Gd complex or cell toxicity was observed during its
      incubation in aqueous environment. Excellent display of rat and tumor
      vascularization was achieved with Gd-DTPA-HSA and HE-24.8; however, contrast of
      vessels was higher in HE-24.8-enhanced scans. HE-24.8 is considered a
      macromolecular contrast agent highly suited for experimental MR studies.

PMID- 16417251
TI  - Carbohydrate and protein immobilization onto solid surfaces by sequential Diels
      Alder and azide-alkyne cycloadditions.
AB  - We demonstrate the applicability of sequential Diels-Alder and azide-alkyne [3 +
      2] cycloaddition reactions (click chemistry) for the immobilization of
      carbohydrates and proteins onto a solid surface. An alpha,omega-poly(ethylene
      glycol) (PEG) linker carrying alkyne and cyclodiene terminal groups was
      synthesized and immobilized onto an N-(epsilon-maleimidocaproyl) (EMC)
      functionalized glass slide via an aqueous Diels-Alder reaction. In the process,
      an alkyne-terminated PEGylated surface was provided for the conjugation of azide
      containing biomolecules via click chemistry, which proceeded to completion at low
      temperature and in aqueous solvent. As anticipated, alkyne, azide, cyclodiene,
      and EMC are independently stable and do not react with common organic reagents
      nor functional groups in biomolecules. Given an appropriate PEG linker,
      sequential Diels-Alder and azide-alkyne [3 + 2] cycloaddition reactions provide
      an effective strategy for the immobilization of a wide range of functionally
      complex substances onto solid surfaces.

PMID- 16417252
TI  - Bright oligothiophene N-succinimidyl esters for efficient fluorescent labeling of
      proteins and oligonucleotides.
AB  - The synthesis of multicolor fluorescent oligothiophene N-succinimidyl esters
      (TSEs) is reported, and their optical properties are discussed with the aid of ab
      initio calculations. The esters were coupled to proteins and to 3'-amino-modified
      oligonucleotides in mild conditions and with similar modalities. A comparative
      study of the bioconjugate of IgG1 anti-CD3 antibody labeled with a blue
      fluorescent TSE and with fluorescein isothiocyanate (FITC) is reported, showing
      that the former achieves higher photoluminescence intensity and optical stability
      than the latter. Fluorescence resonance energy transfer experiments with TSE
      labeled oligonucleotides and examples of cellular imaging via TSE-labeled
      proteins are reported.

PMID- 16417253
TI  - Improved biodistribution and radioimmunoimaging with poly(ethylene glycol)-DOTA
      conjugated anti-CEA diabody.
AB  - Diabodies are single chain antibody fragments (scFvs) that spontaneously form
      bivalent dimers of molecular size 50-55000. Radiolabeled diabodies are almost
      ideal tumor targeting agents due to their high avidity (bivalent) binding to
      tumor antigens and small size (50-55000) that leads to improved tumor-to-blood
      ratio compared to intact antibodies (150000). However, due to their high
      retention and metabolism in the kidney, radioiodine is the current radiolabel of
      choice for diabodies since radioiodine is rapidly excreted from the kidney once
      metabolized. We have previously shown that 111In-DOTA-diabody gives higher tumor
      uptake in nude mouse xenografts than 125I-diabody, but has extremely high kidney
      retention since its 111In-labeled metabolites are retained by and only slowly
      excreted from the kidney. When a diabody is conjugated to a bifunctional PEG-3400
      derivative followed by reaction with cysteinyl-DOTA, the resulting product has an
      apparent molecular size of 75000 and a Stokes radius of 35 angstroms on size
      exclusion chromatography, compared to a Stokes radius of 25 angstroms for intact
      diabody. When radiolabeled, the conjugate gives high yields of 111In-labeled
      product, retains high immunoreactivity, and gives improved biodistributions (30
      40%ID/g, 12-48 h) compared to 111In-DOTA-diabody (12-13%ID/g, 6-12 h). We show
      that the improved biodistribution is due to an increase in Stokes radius caused
      by the linear PEG-3400 since conjugation of diabody with multiple (PEG)12 linkers
      followed by reaction with cysteinyl-DOTA does not reduce kidney accumulation. We
      also show that 111In-cysteinyl-DOTA-PEG3400-diabody gives excellent tumor images
      in the nude mouse xenograft model and that 125I-PEG3400-diabody gives equivalent
      images to 125I-minibody (molecular size, 80000), but improved tumor-to-liver
      ratios, suggesting that this imaging agent can be used to image liver metastases.

PMID- 16417254
TI  - Tunable DNA release from cross-linked ultrathin DNA/PLL multilayered films.
AB  - A novel ultrathin enzymatically degradable multilayered film using DNA as
      building blocks was fabricated by the layer-by-layer (LbL) technique. The UV-vis
      spectrometry and AFM experiments showed that the buildup of DNA and poly-L-lysine
      (PLL) was a kind of "exponentially growing films". The dye adsorption experiment
      suggested that the DNA molecules in the multilayered films were effectively
      protected by PLL. The films were further cross-linked by glutaraldehyde (GA). The
      cross-linking density of the films was modulated through the simple controlling
      of the time of the GA incubation process. An in vitro enzymatic degradation was
      carried out to investigate the DNA release profiles. The UV-vis spectrometry and
      fluorescence measurements indicated that the DNA release profiles were
      accordingly changed with the cross-linking density of the films. The nanoscale,
      easily processed enzymatically biodegradable PLL/DNA film with the ability to
      precisely control DNA release profiles may serve as a novel DNA delivery system,
      which may have great potential for gene therapy applications in implantable
      materials and biomedical devices.

PMID- 16417255
TI  - Ferrocene-assisted stabilization of collagen mimetic triple helices: solid-phase
      synthesis and structure.
AB  - A series of ferrocene-containing collagen models Fc-CO-(Pro-Hyp-Gly)n-Cys (n = 4
      (1), 6 (2), 7 (3), 8 (4), 9 (5)) were synthesized by solid-phase synthesis.
      Biophysical studies using circular dichroism (CD) show that these collagen
      analogues form triple-helical conformations, and the peptides showed a range of
      thermal stabilities ((T(m)), 38-74 degrees C). Results also indicate that the
      ferrocene (Fc)-labeled collagen models possesses a higher triple-helical
      propensity than the unlabeled collagen models as demonstrated by the higher
      melting temperatures and thermodynamic parameters, and we conclude that the Fc
      group at the N-terminal position of the peptide strands increases the stability
      of the triple helix.

PMID- 16417256
TI  - Intracellular traffic and fate of protein transduction domains HIV-1 TAT peptide
      and octaarginine. Implications for their utilization as drug delivery vectors.
AB  - Transduction domains such as those derived from the HIV-TAT protein are candidate
      vectors for intracellular delivery of therapeutic macromolecules such as DNA and
      proteins. The mechanism by which they enter cells is controversial, and very
      little spatial information regarding the downstream fate of these peptides from
      the plasma membrane is available. We studied endocytic traffic of fluorescent
      conjugates of HIV-TAT peptide and octaarginine in human hematopoietic cell lines
      K562 (CD34-) and KG1a (CD34+) and substantiated our findings in epithelia cells.
      Both peptides were efficiently internalized to endocytic pathways of both
      hematopoietic cell lines; however, comparative analysis of the intracellular
      location of the peptides with endocytic probes revealed major differences in
      spatial organization of their endocytic organelles and their interaction with the
      peptides at low temperatures. Double labeling confocal microscopy demonstrates
      that prelabeled lysosomes of all the tested cells are accessible to internalized
      peptides within 60 min of endocytic uptake. Incubation of cells with nocodazole
      and cytochalasin D inhibited peptide traffic from early to late endosomal
      structures, demonstrating a cytoskeletal requirement for lysosomal delivery.
      Disruption of Golgi and endoplasmic reticulum dynamics was without effect on
      peptide localization, suggesting that endosomes and lysosomes rather than these
      organelles are the major acceptor compartments for these molecules.

PMID- 16417257
TI  - Poly(glycoamidoamine)s for gene delivery: stability of polyplexes and efficacy
      with cardiomyoblast cells.
AB  - Polymeric vectors have potential as nucleic acid delivery vehicles for novel gene
      therapy and oligonucleotide treatments for cardiovascular disease. In this
      report, poly(glycoamidoamine)s that contain four secondary amines and either two
      or four hydroxyl units in the repeat unit with D-glucarate (D4), meso-galactarate
      (G4), D-mannarate (M4), and l-tartarate (T4) stereochemistry have been
      investigated for their pDNA-binding affinity, DNase protection effect, and
      polyplex stability in the presence of salt and serum. Also, the luciferase gene
      delivery and cellular internalization of polyplexes formed with these polymers
      have been investigated with rat cardiomyoblast [H9c2(2-1)] cells. The results
      demonstrate that the number of hydroxyl groups and the stereochemistry affect the
      biological properties. Polymers T4 and G4 have higher pDNA binding affinity,
      protect pDNA from nuclease degradation, and do not release pDNA in the presence
      of serum. Polymers D4 and M4 bind pDNA with lower affinity, which allows for some
      pDNA degradation and release in the presence of serum. Although T4 forms the most
      stable polyplexes, vector G4 reveals the highest luciferase gene expression in
      serum-free media and the greatest cellular internalization of fluorescein-labeled
      pDNA both in serum-free and serum-supplemented media. The results of these
      studies indicate that the polymer-DNA binding affinity, nuclease protection
      capability, and polyplex stability are important parameters to facilitate
      effective pDNA delivery with poly(glycoamidoamine)s in cultured cardiomyoblast
      cells. The carbohydrate type also plays an important role to increase cellular
      uptake and gene expression where the polymer with the galactarate stereochemistry
      (in G4) is found to be the most effective vector for pDNA delivery to
      cardiomyoblast cells in vitro.

PMID- 16417258
TI  - Development of nanoparticle libraries for biosensing.
AB  - Magnetic and magnetofluorescent nanoparticles have become important materials for
      biological applications especially for sensing, separation, and imaging. To
      achieve target specificity, these nanomaterials are often covalently modified
      with binding proteins such as antibodies or proteins. Here we report on the
      creation of nanoparticle libraries that achieve specificity through multivalent
      modification with small molecules. We explore different synthetic routes to
      attach small molecules with anhydride, amine, hydroxyl carboxyl, thiol, and epoxy
      handles. We show that the derived nanomaterials have unique biological functions,
      possess different behaviors in cell screens, and can be used as substrates for
      biological screens.

PMID- 16417260
TI  - Linear polyethyleneimine grafted to a hyperbranched poly(ethylene glycol)-like
      core: a copolymer for gene delivery.
AB  - A block copolymer of a hyperbranched poly(ethylene glycol)-like core and linear
      polyethylenimine (HBP) was synthesized by a facile synthetic route that included
      (1) a single-step cationic copolymerization of diepoxy and polyhydroxyl monomers,
      (2) derivatization of hydroxyl groups of the core HBPEG copolymer with either
      tosyl or chloromethylbenzoyl chlorides resulting in a corresponding
      macroinitiator, and (3) synthesis of HBPEG-block-poly(alkyl oxazolines). HBPEG
      block-linear polyethyleneimine (HBP) was obtained by hydrolysis of HBPEG-block
      poly(alkyl oxazolines). Linear PEI-bearing hyperbranched polycations (HBP) had
      lower inherent toxicity in cell culture than PEG-grafted linear
      polyethyleneimines (PEGLPEI). PEGLPEI formed a complex with DNA with an average
      diameter of 250 nm. The complexes were loosely condensed and formed aggregates
      and precipitates during storage. By contrast, hyperbranched polycations (HBP)
      formed approximately 50 nm nanocomplexes with DNA that were stable for several
      weeks and showed resistance to DNAse I-mediated degradation. The 'inverted' block
      copolymers showed several orders of magnitude higher transfection efficiency than
      PEGLPEI in vitro. Because of the biocompatibility and higher transfection
      efficiency, the 'inverted' block copolymer merits further investigation as a gene
      carrier.

PMID- 16417259
TI  - Enhanced activity of monomethylauristatin F through monoclonal antibody delivery:
      effects of linker technology on efficacy and toxicity.
AB  - We have previously shown that antibody-drug conjugates (ADCs) consisting of cAC10
      (anti-CD30) linked to the antimitotic agent monomethylauristatin E (MMAE) lead to
      potent in vitro and in vivo activities against antigen positive tumor models.
      MMAF is a new antimitotic auristatin derivative with a charged C-terminal
      phenylalanine residue that attenuates its cytotoxic activity compared to its
      uncharged counterpart, MMAE, most likely due to impaired intracellular access. In
      vitro cytotoxicity studies indicated that mAb-maleimidocaproyl-valine-citrulline
      p-aminobenzyloxycarbonyl-MMAF (mAb-L1-MMAF) conjugates were >2200-fold more
      potent than free MMAF on a large panel of CD30 positive hematologic cell lines.
      As with cAC10-L1-MMAE, the corresponding MMAF ADC induced cures and regressions
      of established xenograft tumors at well tolerated doses. To further optimize the
      ADC, several new linkers were generated in which various components within the L1
      linker were either altered or deleted. One of the most promising linkers
      contained a noncleavable maleimidocaproyl (L4) spacer between the drug and the
      mAb. cAC10-L4-MMAF was approximately as potent in vitro as cAC10-L1-MMAF against
      a large panel of cell lines and was equally potent in vivo. Importantly, cAC10-L4
      MMAF was tolerated at >3 times the MTD of cAC10-L1-MMAF. LCMS studies indicated
      that drug released from cAC10-L4-MMAF was the cysteine-L4-MMAF adduct, which
      likely arises from mAb degradation within the lysosomes of target cells. This new
      linker technology appears to be ideally suited for drugs that are both relatively
      cell-impermeable and tolerant of substitution with amino acids. Thus, alterations
      of the linker have pronounced impacts on toxicity and lead to new ADCs with
      greatly improved therapeutic indices.

PMID- 16417261
TI  - RNAi silencing of exogenous and endogenous reporter genes using a macrocyclic
      octaamine as a "compact" siRNA carrier. Studies on the nonsilenced residual
      activity.
AB  - A macrocyclic octaamine 1 having a covalently linked lipid-bundle structure was
      introduced as a new type of siRNA carrier. Gel electrophoresis, DLS, and SPR
      results indicate that it strongly binds to a luciferase-targeting 21-mer (42P)
      siRNA with a ratio of 1/P congruent with 0.3 (1/N congruent with 2.4) to give
      remarkably compact 1-siRNA complexes with an average size of approximately 10 nm.
      The 1-mediated siRNA silencing of the exogenous luciferase gene occurs with a 90
      95% efficiency. The overall suppression-[siRNA] profile with a 5-10% residual
      activity in the saturation region is commonly observed irrespective of the cell
      type (HeLa, HepG2, or HEK293), the order, or timing (stepwise or simultaneous) of
      supply of the siRNA and that of the luciferase-encoding plasmid, the level of
      mRNA transcribed, or the type of carriers (1 vs lipofectamine 2000). The
      silencing of the endogenous DsRed2 gene stably incorporated in the genome of HeLa
      cells also has a similar overall profile. These results suggest that (1) the
      cellular uptake of the plasmid and that of the siRNA are basically independent of
      each other and (2) the incomplete silencing is not due to insufficient siRNA
      delivery. Implication of item 2 is briefly discussed.

PMID- 16417262
TI  - Biodegradable nanoparticles for direct or two-step tumor immunotargeting.
AB  - In this study, selective cancer cell targeting of biodegradable poly(lactic acid)
      (PLA) nanoparticles (NPs) has been investigated in vitro. SKOV-3 (HER2 positive)
      ovarian cancer and Daudi (CD20 positive) lymphoma cell targeting was mediated by
      anti-HER2 (trastuzumab, Herceptin) and anti-CD20 (rituximab, Mabthera) monoclonal
      antibodies (mAbs), respectively. The mAb against nonexpressed antigen serving on
      each cell as isotype matched irrelevant control. Two different targeting
      approaches have been studied, a direct method using antibody-labeled NPs (mAb
      NPs) and a pretargeting method using the avidin-biotin technology. For the direct
      protocol, fluorescent PLA-NPs were prepared including 10% 1-pyrenebutanol (PB)
      labeled PLA in the NP-preparation (PB-NP). Thiol groups were covalently bound to
      the PB-NP, and the resulting thiolated PB-NP were coupled with the two mAbs using
      a bifunctional cross-linker. The effective targeting of cells by mAb-PB-NP was
      shown by flow cytometry analysis. Clearly anti-HER2-PB-NP specifically bound to
      the SKOV-3 cells and not to the Daudi cells, while anti-CD20-PB-NPs bound to
      Daudi cells but not to SKOV-3 cells. Specific mAb-PB-NP binding to tumor cells
      produced a mean 10-fold or higher signal increase compared to irrelevant IgG-PB
      NPs. For the pretargeting protocol, plain PLA-NPs were also thiolated and
      NeutrAvidin-Rhodamine Red-X (NAR) coupled to the functionalized PLA-NPs with
      sulfo-MBS. The two-step method was evaluated in vitro by incubating SKOV-3 cells
      first with biotinylated mAbs followed by NAR-NPs. The relative fluorescence
      associated to the specific binding of NPs produced a 6-fold increase in flow
      cytometry signal compared to nonspecific binding. In conclusion, these
      experiments have shown that NPs covalently coupled with antibodies or NAR can
      specifically and efficiently bind to cancer cells in both a pretargeting and a
      direct approach, suggesting that functionalized NPs may be a useful drug carrier
      for tumor targeting.

PMID- 16417263
TI  - Human serum albumin hybrid incorporating tailed porphyrinatoiron(II) in the
      alpha,alpha,alpha,beta-conformer as an O2-binding site.
AB  - We have found that recombinant human serum albumin (HSA) incorporating tailed
      porphyrinatoiron(II) in the alpha,alpha,alpha,beta-conformer can reversibly bind
      and release O2 under physiological conditions (pH 7.3, 37 degrees C) like
      hemoglobin and myoglobin. beta-2-Methylimidazolyl-tailed porphyrinatoirons (6a,
      6b) are synthesized via four steps from the atropisomers of tetrakis(o
      aminophenyl)porphyrin. The stereochemistry of the alpha,alpha,alpha,beta
      conformer has been determined by NMR spectroscopy. 6a and 6b form stable O2
      adduct complexes in toluene solution at room temperature. The association rate
      constants of O2 are 3.1- and 1.9-fold lower than those of the corresponding
      alpha,alpha,alpha,alpha-conformers (1a, 1b), indicating that the three
      substituents (cyclohexanamide or pivalamide groups) are close to each other on
      the porphyrin platform and construct a narrow encumbrance around the O2
      coordination site. Although 6a and 6b are incorporated into the hydrophobic
      domains of HSA to produce the albumin-heme hybrid, only HSA-6a can bind O2 in
      aqueous medium. The cyclohexanamide fences are necessary for the tailed
      porphyrinatoiron to form a stable O2-adduct complex under physiological
      conditions. The O2-binding affinity (P(1/2)) of HSA-6a is 45 Torr (37 degrees C),
      and the O2 transporting efficiency between lungs and muscle tissues in the human
      body is estimated to be identical to that of human red blood cells. The HSA-6a
      solution will become one of the most promising materials for red blood cell
      substitutes, which can be manufactured on an industrial scale.

PMID- 16417264
TI  - PEI-g-chitosan, a novel gene delivery system with transfection efficiency
      comparable to polyethylenimine in vitro and after liver administration in vivo.
AB  - Polyethylenimine-graft-chitosan (PEI-g-chitosan) was synthesized by performing
      cationic polymerization of aziridine in the presence of water-soluble oligo
      chitosan (M(n) = 3400). The absolute molecular weight and chemistry of the PEI-g
      chitosan obtained were characterized using GPC, 13C and 1H NMR, respectively. The
      results indicated that all the amines of chitosan were grafted with oligo-PEI,
      and the average length of the oligo-PEI side chains was determined by the feed
      molar ratio of aziridne/amine in chitosan. PEI-g-chitosan of M(n) = 7400 with a
      polydispersity index (PDI) of 1.50, and PEI side chains of M(n) = 206 was
      prepared for gene delivery. Gel electrophoresis showed that DNA migration was
      retarded completely at a N/P ratio of 2.5/1, indicating good DNA condensation
      capability of PEI-g-chitosan. The sizes and the zeta-potentials of the complexes
      of PEI-g-chitosan/DNA were characterized. The cytotoxicity of PEI-g-chiotsan was
      evaluated, and the results reflected that PEI-g-chitosan had a lower cytotoxicity
      than PEI (25 K). Gene transfection efficiency of PEI-g-chitosan in HepG2, HeLa,
      and primary hepatocytes cells and after administration in the common bile duct of
      rat liver was determined. Remarkably, PEI-g-chitosan showed a higher transfection
      efficiency than that of PEI (25 K) both in vitro and in vivo. The systematic
      distribution and the distribution in liver of the gene expression of the
      complexes of PEI-chitosan/DNA were determined as well.

PMID- 16417265
TI  - In vitro gene transfer efficacies and serum compatibility profiles of novel mono
      , di-, and tri-histidinylated cationic transfection lipids: a structure-activity
      investigation.
AB  - Recently, we demonstrated that covalent grafting of an endosome-disrupting single
      histidine functionality in the headgroup region imparts high gene transfer
      properties to cationic amphiphiles (Kumar, V. V., et al. Gene Ther. 2003, 10,
      1206-1215). However, whether covalent attachment of multiple histidine
      functionalities in the headgroup region are capable of further enhancing the gene
      transfer efficacies of cationic amphiphiles remains to be explored. To this end,
      herein, we report on the design, syntheses, physicochemical characterizations, in
      vitro gene transfer properties, and serum compatibilities of three novel nontoxic
      cationic transfection amphiphiles containing mono-, di-, and tri-histidine
      functionalities in their headgroup regions (lipids 1-3) in multiple cultured
      cells. Significantly, findings in both the reporter gene expression assay and the
      whole cell histochemical X-gal staining assay support the notion that there is no
      linear correlation between the in vitro transfection efficacies and the number of
      histidine functionalities in the polar headgroup regions for histidinylated
      cationic amphiphiles. The relative gene transfer efficiencies, as well as the
      serum compatibilities, of the present histidinylated cationic amphiphiles were
      found to be strikingly dependent on the medium of lipoplex formation. Most
      importantly, high serum compatibilities (up to 50% added serum) of the lipoplexes
      of lipids 1 and 3 make them promising nonviral transfection vectors for future
      systemic applications.

PMID- 16417266
TI  - Dendrons with spermine surface groups as potential building blocks for nonviral
      vectors in gene therapy.
AB  - This paper investigates a series of dendrons based on the Newkome dendritic
      scaffold that displays a naturally occurring polyamine (spermine) on their
      surface. These dendrons have previously been shown to interact with DNA in a
      generation dependent manner with the more highly branched dendrons exhibiting a
      strong multivalency effect for the spermine surface groups. In this paper, we
      investigate the ability of these dendrons to transfect DNA into cells (human
      breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as
      determined by the luciferase assay. Although the dendrons are unable to transfect
      DNA in their own right, they are capable of delivering DNA in vitro when
      administered with chloroquine, which assists with escape from endocytic vesicles.
      The cytotoxicity of the dendrons was determined using the XTT assay, and it was
      shown that the dendrons were nontoxic either alone or in the presence of DNA.
      However, when administered with DNA and chloroquine, the most highly branched
      dendron did exhibit some cytotoxicity. This paper elucidates the relationship
      between in vitro transfection efficiency and toxicity. While transfection
      efficiencies are modest, the low toxicity of the dendrons, both in their own
      right, and in the presence of DNA, provides encouragement that this type of
      building block, which has a relatively high affinity for DNA, will provide a
      useful starting point for the further synthetic development of more effective
      gene transfection agents.

PMID- 16417268
TI  - Cellular delivery of polyheteroaromate-peptide nucleic acid conjugates mediated
      by cationic lipids.
AB  - In the search of facile and efficient methods for PNA cellular delivery, we have
      tested a series of PNA conjugates based on (hetero) aromatic, lipophilic
      compounds such as 9-aminoacridine, benzimidazoles, carbazole, anthraquinone,
      porphyrine, psoralen, pyrene, and phenyl-bis-benzimidazole ("Hoechst"). These
      chemically modified PNAs were delivered to cultured pLuc705HeLa cells mediated by
      cationic liposomes (LipofectAMINE or LiofectAMINE2000), and their nuclear
      delivery was inferred from induced luciferase activity as a consequence of pre
      mRNA splicing correction by the antisense-PNA. PNAs modified with 9
      aminoacridine, "Hoechst", or acetyl-"Hoechst" showed highest antisense activities
      (while unmodified PNA failed to show any significant antisense activity). In
      particular, bis-acridine-conjugated PNA showed nearly 60% splicing correction at
      250 nM concentration in combination with LipofectAMINE2000. Interestingly,
      relative differences between the derivatives were observed when LipofectAMINE was
      used as compared to LipofectAMINE2000, but in general the latter yielded the
      higher antisense activity. The most active modifications of these PNA constructs
      were further tested for antisense down-regulation of luciferase in p53R cells in
      order to evaluate the cytoplasmic activity (uptake) of the PNAs. A dose-dependent
      down regulation of luciferase was demonstrated also in this system. The PNA
      conjugated to acetyl-Hoechst caused a reduction of luciferase activity to less
      than 40% of the control at a concentration of 1 muM. These results indicate that
      conjugation of (hetero) polyaromatic compounds to PNA can dramatically improve
      liposome-mediated cellular delivery both to cytoplasm as well as to the nucleus.
      However, no clear structure/activity relations are apparent from the present
      results, except that both 9-aminoacridine and "Hoechst" are also nucleic acid
      binding ligands.

PMID- 16417267
TI  - N-terminally PEGylated human interferon-beta-1a with improved pharmacokinetic
      properties and in vivo efficacy in a melanoma angiogenesis model.
AB  - PEGylation of IFN-alpha has been used successfully to improve the pharmacokinetic
      properties and efficacy of the drug. To prepare a PEGylated form of human
      interferon-beta-1a (IFN-beta-1a) suitable for testing in vivo, we have
      synthesized 20 kDa mPEG-O-2-methylpropionaldehyde and used it to modify the N
      terminal alpha-amino group of the cytokine. The PEGylated protein retained
      approximately 50% of the activity of the unmodified protein and had significantly
      improved pharmacokinetic properties following intravenous administration in rats.
      The clearance and volume of distribution at steady state were reduced
      approximately 30-fold and approximately 4-fold, respectively, resulting in a
      significant increase in systemic exposure as determined by the area under the
      curve. The elimination half-life of the PEGylated protein was approximately 13
      fold greater than for the unmodified protein. The unmodified and PEGylated
      proteins were tested for their ability to inhibit the formation of radially
      oriented blood vessels entering the periphery of human SK-MEL-1 melanoma tumors
      in athymic nude homozygous (nu/nu) mice. In a single dose comparison study,
      administration of 1 x 10(6) units of unmodified IFN-beta-1a resulted in a 29%
      reduction in vessel number, while 1 x 10(6) units of PEGylated IFN-beta-1a
      resulted in a 58% reduction. Both treatments resulted in statistically
      significant reductions in mean vessel number as compared to the vehicle (control)
      treated mice, with the PEGylated IFN-beta-1a-treated mice showing a statistically
      significantly greater reduction in mean vessel number as compared to the
      unmodified IFN-beta-1a-treated mice. In a multiple versus single dose comparison
      study, daily administration of 1 x 10(6) units of unmodified IFN-beta-1a for 9
      days resulted in a 51% reduction in vessel number, while a single dose of 1 x
      10(6) units of the PEGylated protein resulted in a 66% reduction. Both treatments
      resulted in statistically significant reductions in mean vessel number as
      compared to the vehicle-treated mice, with the PEGylated IFN-beta-1a-treated mice
      showing a statistically significantly greater reduction in mean vessel number as
      compared to the unmodified IFN-beta-1a-treated mice. Therefore, the improved
      pharmacokinetic properties of the modified protein translated into improved
      efficacy. Since unmodified IFN-beta is used for the treatment of multiple
      sclerosis and hepatitis C virus infection, a PEGylated form of the protein such
      as 20 kDa mPEG-O-2-methylpropionaldehyde-modified IFN-beta-1a may serve as a
      useful adjunct for the treatment of these diseases. In addition, the
      antiangiogenic effects of PEGylated IFN-beta-1a may be harnessed for the
      treatment of certain cancers, either as a sole agent or in combination with other
      antitumor drugs.

PMID- 16417269
TI  - Synthesis and evaluation of glycosylated octreotate analogues labeled with
      radioiodine and 211At via a tin precursor.
AB  - Carbohydration of N-terminus and substitution of a threonine for the threoninol
      residue at the C-terminus of Tyr3-octreotide (TOC) has resulted in improved
      pharmacokinetics and tumor targeting of its radioiodinated derivatives. Yet,
      these peptides are very susceptible to in vivo deiodination due to the similarity
      of monoiodotyrosine (MIT) to thyroid hormone. The goal of this work was to
      develop octreotate analogues containing both a sugar moiety and a nontyrosine
      prosthetic group on which a radioiodine or 211At can be introduced. Solid-phase
      synthesis and subsequent modifications delivered an iodo standard of the target
      peptide N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(3-iodobenzoyl)-Lys0-octreotate
      (GIBLO) and the corresponding tin precursor N(alpha)-(1-deoxy-D-fructosyl)
      N(epsilon)-[(3-tri-n-butylstannyl)benzoyl]-Lys0-octreotate (GTBLO). GIBLO
      displaced [125I]TOC from somatostatin receptor subtype 2 (SSTR2)-positive AR42J
      rat pancreatic tumor cell membranes with an IC50 of 0.46 +/- 0.05 nM suggesting
      that GIBLO retained affinity to SSTR2. GTBLO was radiohalogenated to [131I]GIBLO
      and N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(3-[211At]astatobenzoyl)-Lys0
      octreotate ([211At]GABLO) in 21.2 +/- 4.9% and 46.8 +/- 9.5% radiochemical
      yields, respectively. From a paired-label internalization assay using D341 Med
      medulloblastoma cells, the maximum specific internalized radioactivity from
      [131I]GIBLO was 1.78 +/- 0.8% of input dose compared to 9.67 +/- 0.43% for
      N(alpha)-(1-deoxy-D-fructosyl)-[125I]iodo-Tyr3-octreotate ([125I]I-Gluc-TOCA).
      Over a 4 h period, the extent of internalization of [131I]GIBLO and [211At]GABLO
      was similar in this cell line. In D341 Med murine subcutaneous xenografts, the
      uptake of [125I]I-Gluc-TOCA at 0.5, 1 and 4 h was 21.5 +/- 4.0% ID/g, 18.8 +/-
      7.7% ID/g, and 0.9 +/- 0.4% ID/g, respectively. In comparison, these values for
      [131I]GIBLO were 6.9 +/- 1.2% ID/g, 4.7 +/- 1.4% ID/g, and 0.8 +/- 0.5% ID/g.
      Both in vitro and in vivo catabolism studies did not suggest the severance of the
      lys0 along with its appendages from the peptide. Taken together, although GIBLO
      maintained affinity to SSTR2, its tumor uptake both in vitro and in vivo was
      substantially lower than that of I-Gluc-TOCA suggesting other factors such as net
      charge and overall geometry of the peptide may be important.

PMID- 16417270
TI  - Use of the Sonogashira coupling reaction for the "two-step" labeling of
      phenylalanine peptide side chains with organometallic compounds.
AB  - The Pd-catalyzed Sonogashira coupling of ferrocene alkyne derivatives as metal
      probes to iodophenylalanine containing peptides is described. 4-Iodophenylalanine
      was incorporated into dipeptides and the neuropeptide [Leu5]-enkephalin (Enk) by
      solid phase peptide synthesis, thereby creating a functional group suitable for
      the Sonogashira coupling. The reaction with two different ferrocene alkynes
      resulted in the corresponding ferrocene-labeled derivatives, which were obtained
      in good yield and purity. All new compounds were comprehensively characterized,
      including elemental analysis, 1D and 2D NMR, EI-, FAB- or ESI-MS, IR and UV-vis
      spectroscopy, and electrochemistry of the ferrocene label. Unlike well
      established conjugation methods for peptide side chains such as lysine and
      cystein, the phenyl group in Phe is not readily available for derivatization.
      This work presents a versatile procedure for the regioselective introduction of
      an organometallic label into biologically relevant peptides as exemplified for
      enkephalin.

PMID- 16417271
TI  - PNA-nitrogen mustard conjugates are effective suppressors of HER-2/neu and
      biological tools for recognition of PNA/DNA interactions.
AB  - Peptide nucleic acids (PNAs) are promising tools for gene regulation. One of the
      challenges of using PNAs as gene regulators is the need to optimize the
      efficiency of interaction with critical sequences of DNA. To improve the
      efficiency of binding between PNAs and the HER-2/neu promoter, mono- and bis
      pyrimidine-rich PNAs were conjugated to a nitrogen mustard at either the amino or
      carboxy terminus. Gel shift analysis demonstrated that conjugation to an
      alkylating agent slowed PNA binding and favored PNA:DNA:DNA triplex helix
      formation while preserving a high binding affinity. Sites of DNA alkylation were
      visualized by piperidine cleavage and showed PNA binding first by Hoogsteen bond
      formation with the target duplex to form a stable PNA:DNA:DNA triplex structure
      which is later converted to a PNA:DNA:PNA triple helix by strand invasion and
      Watson-Crick base pairing by a second PNA molecule. In this way, PNA-directed DNA
      alkylation was used to deduce the mode of PNA binding. Transient transfection
      experiments demonstrated that the PNA-nitrogen mustard conjugates suppressed HER
      2/neu expression by up to 80%. In comparison with an unmodified mono-PNA or a bis
      PNA, these results indicate that the covalent adducts stabilized PNA binding in
      cells and suggest that the conjugation of PNAs to nitrogen mustards is a robust
      strategy for developing antigene PNA oligonucleotides to prevent transcription.

PMID- 16417272
TI  - Novel and efficient preparation of precursor [188Re(OH2)3(CO)3]+ for the labeling
      of biomolecules.
AB  - A novel and efficient method for preparing 188Re(I) tricarbonyl precursor
      [188Re(OH2)3(CO)3]+ has been developed by reacting [188Re]perrhenate with
      Schibli's kit in the presence of borohydride exchange resin (BER) as a reducing
      agent and an anion scavenger. The precursor was produced in more than 97% yield
      by reacting a solution of tetrahydroborate exchange resin (BER, 3 mg), borane
      ammonia (BH3.NH3, 3 mg), and potassium boranocarbonate (K2[H3BCO2], 3 mg) in 0.9%
      saline with a solution of sodium perrhenate (Na188ReO4) with up to 50 MBq and
      concentrated phosphoric acid (85%, 7 microL) at 60 degrees C for 15 min. HPLC and
      TLC revealed 0% unreacted [188Re]perrhenate ion and <3% of colloidal 188ReO2.
      Since the precursor is produced with high radiochemical purity and labeling
      efficiency under the milder conditions than those required for the conventional
      reducing agents, the latter can be replaced.

PMID- 16417273
TI  - A solid-phase labeling strategy for the preparation of technetium and rhenium
      bifunctional chelate complexes and associated peptide conjugates.
AB  - A new solid-phase labeling strategy for the preparation of (99m)Tc and Re chelate
      complexes and associated peptide derivatives, was developed. Resin-bound
      monoamide monoamine (MAMA) chelates were prepared in such a manner that upon the
      addition of a suitable Re(V) and Tc(V) precursor the target metal complexes were
      selectively released from the resin. The desired products were isolated from
      unreacted ligand by a simple filtration/solid-phase extraction procedure. In
      addition to the preparation of a series of functionalized ligands, a peptide
      conjugate was constructed from one of the resin-bound chelates using a
      conventional automated peptide synthesizer. The yields of the Re chelate
      complexes were typically greater than 70%, while the maximum yield for reactions
      run at the tracer level using (99m)Tc was 50%. The reported approach has a number
      of attractive features, including the opportunity to prepare libraries of novel
      agents, the ability to isolate macroscopic amounts of Re complexes for use in in
      vitro screening studies and as well-characterized standards for tracer level
      work, and the ability to produce (99m)Tc complexes that are free of any unreacted
      starting material without having to employ preparative HPLC.

PMID- 16417274
TI  - Encapsulation of myoglobin with a mesoporous silicate results in new
      capabilities.
AB  - A metmyoglobin (Fe3+), an oxidized form of myoglobin (Fe2+), was confined in
      nanospaces of about 4 nm in diameter in mesoporous silica (FSM; folded-sheet
      mesoporous material), forming a metmyoglobin (Fe3+)-FSM nanoconjugate. The
      spectral characteristics of metmyoglobin (Fe3+)- and myoglobin (Fe2+)-FSM show an
      absorption curve quite similar to that of native metmyoglobin, indicating that
      myoglobin retains its higher-order structure in the pores of FSM. The
      metmyoglobin (Fe3+)-FSM conjugate had not only a peroxidase-like activity in the
      presence of hydrogen peroxide (a hydrogen acceptor) and 2,2-azino-bis(3
      ethylbenzothiazoline)-6-sulfomic acid (ABTS) or guaiacol (a hydrogen donor) but
      also an advanced molecular recognition ability enabling it to distinguish between
      ABTS and guaiacol. Furthermore, the metmyoglobin (Fe3+)-FSM showed the peroxidase
      like activity even in an organic media using benzoyl peroxide as the hydrogen
      acceptor and leucocrystal violet as the hydrogen donor. The simple immobilization
      of metmyoglobin (Fe3+) into FSM results in enhanced catalytic activity in organic
      media compared to that of native metmyoglobin (Fe3+).

PMID- 16417275
TI  - Comparative evaluation of target-specific GFP gene silencing efficiencies for
      antisense ODN, synthetic siRNA, and siRNA plasmid complexed with PEI-PEG-FOL
      conjugate.
AB  - Cell specific gene silencing effects of antisense oligodeoxynucleotide (AS-ODN),
      synthetic small interfering RNA (siRNA-S), and siRNA expressing plasmid (siRNA-P)
      were comparatively evaluated. Poly(ethylenimine) (PEI) and PEI-graft
      poly(ethylene glycol)-folate (PEI-PEG-FOL) conjugate were used to form nanosized
      polyelectrolyte complexes with the above three nucleic acids coding for
      inhibition of green fluorescent protein (GFP) expression. The three nucleic acid
      complexes formulated with either PEI or PEI-PEG-FOL had comparable sizes and
      surface zeta potential values. Among the three inhibitory nucleic acids, siRNA-S,
      when complexed with PEI-PEG-FOL, exhibited the most dose-effective and fastest
      gene silencing effect for FOL receptor overexpressing KB cells, because the siRNA
      S could be directly delivered, via FOL receptor-mediated endocytosis, into the
      cytoplasm compartment where the degradation processing of target GFP mRNA
      occurred in a sequence-specific manner.

PMID- 16417276
TI  - Microstructured liposome array.
AB  - Conversion of a DNA chip to a nanocapsule array was performed by grafting on a
      liposome an oligonucleotide complementary to an oligonucleotide bound to the
      array. Each liposome may be loaded by a soluble molecule or may present a
      hydrophobic or amphiphilic molecule inserted in its wall. To detect liposomes on
      the chip, we used fluorescent dyes encapsulated in the liposome internal volume
      or fluorescent lipids. We observed that an oligonucleotide-grafted liposome
      containing a defined dye specifically accumulated on the area where its
      complementary oligonucleotide had been spotted on the array. The virtually
      unlimited amount of addresses allows the specific binding of large amounts of
      liposomes in one single batch.

PMID- 16417277
TI  - Synthesis of acid-cleavable light isotope-coded affinity tags (ICAT-L) for
      potential use in proteomic expression profiling analysis.
AB  - A convenient synthesis of some homologous light isotope-coded affinity tags (ICAT
      L) containing an acid-labile moiety between the affinity component biotin and an
      electrophilic polar linker is described. These light ICAT reagents give smooth
      mass spectral signals in tandem mass spectrometry (MS/MS) analyses of some
      commercially available cysteine-containing peptides. However, these ICAT
      molecules are designed for use in identification and relative quantification of
      whole or partially purified cellular and tissue proteomes. Since the biotin
      moiety can be readily cleaved off the reagent after mass tagging, undesired
      residual fragmentation patterns caused by biotin of derived peptides, as normally
      observed using biotin-containing ICAT reagents, are effectively eliminated. This
      strategy should enhance peptide sequence coverage significantly which, in turn,
      should result in improving the quality of data obtained during data-dependent
      peptide mass and tandem mass spectral analysis of whole proteomes.

PMID- 16417278
TI  - Cell bioassay for paralytic shellfish poisoning (PSP): comparison with postcolumn
      derivatization liquid chromatographic analysis and application to the monitoring
      of PSP in shellfish.
AB  - We performed a neuroblastoma cell (Neuro2a) culture assay modified slightly from
      a method reported previously to provide a simple and sensitive evaluation of
      paralytic shellfish poisoning (PSP) toxicity in shellfish. The cell bioassay was
      just as sensitive for C-toxins as for gonyautoxins. The sensitivity of our cell
      bioassay was 4 times that of the current standard mouse bioassay. Using the cell
      bioassay, we evaluated PSP toxicity in 361 shellfish samples collected from
      Mikawa Bay and Ise Bay, Aichi Prefecture, Japan, from April 1999-March 2002. The
      results were compared with those obtained in a postcolumn derivatization liquid
      chromatographic analysis. PSP toxins were detected in 236/361 samples by both
      assays, and there was a fairly good correlation (r = 0.9001, n = 236, p < 0.001)
      between the results from the two assays. We applied this cell bioassay when short
      necked clams in the bay turned poisonous in 2001. The chronological changes in
      PSP toxicity in the short-necked clams were analyzed and compared with those of
      the cell density of poisonous plankton (Alexandrium tamarense) occurring in the
      bay. The PSP toxicity in shellfish peaked 2 weeks after the cell density reached
      a maximum. We recommend using the cell bioassay for routine monitoring of PSP
      toxicity in shellfish living in natural marine environments.

PMID- 16417279
TI  - Liquid chromatography/mass spectrometry and liquid chromatography/nuclear
      magnetic resonance as complementary analytical techniques for unambiguous
      identification of polymethoxylated flavones in residues from molecular
      distillation of orange peel oils (Citrus sinensis).
AB  - Liquid chromatography/mass spectrometry and liquid chromatography/nuclear
      magnetic resonance techniques with ultraviolet/diode array detection were used as
      complementary analytical tools for the reliable identification of
      polymethoxylated flavones in residues from molecular distillation of cold-pressed
      peel oils of Citrus sinensis. After development of a liquid chromatographic
      separation procedure, the presence of several polymethoxy flavones such as
      sinensetin, nobiletin, tangeretin, quercetogetin, heptamethoxyflavone, and other
      derivatives was unambiguously confirmed. In addition, proceranone, an acetylated
      tetranortriterpenoid with limonoid structure, was identified for the first time
      in citrus.

PMID- 16417280
TI  - Study of the influence of alcoholic fermentation and distillation on the oxygen
      18/oxygen-16 isotope ratio of ethanol.
AB  - A laboratory procedure for the analysis of the oxygen-18/oxygen-16 isotope ratios
      of ethanol derived from sugars and fruit juices by pyrolysis-isotope ratio mass
      spectrometry (IRMS) has been applied to the study of isotopic fractionation
      induced by the isotope effects of fermentation and distillation. For both
      processes, an experimental model has been established to describe and explain the
      observed fractionation phenomena. It is shown that reproducible results can be
      obtained when appropriate analytical conditions are used. Moreover, the ability
      of ethanol to act as a reliable indicator of the (18)O/(16)O ratio of sugars in
      orange juice (and therefore to be used as an internal reference for detecting
      water addition) is demonstrated both in theory and in practice.

PMID- 16417281
TI  - An isotopically labeled internal standard liquid chromatography-tandem mass
      spectrometry method for determination of ephedrine alkaloids and synephrine in
      dietary supplements.
AB  - We report a simplified analytical procedure for determination of ephedrine
      alkaloids and synephrine in dietary supplements. Cleanup by simple filtration,
      when combined with tandem mass spectrometry (MS/MS) detection, provided results
      comparable to our published method with solid phase extraction (SPE) cleanup and
      single-stage MS detection with in-source fragmentation. We also compared three
      mass spectrometric experimental configurations: electrospray (ESI) and
      atmospheric pressure chemical ionization (APCI) with MS/MS and APCI-MS with
      fragmentation provided by increasing cone voltage. Because these methods used one
      isotopically labeled internal standard to determine several different analytes,
      quantitation errors may arise from susceptibility to ionization suppression
      caused by the matrix. We therefore compared the results obtained by ESI and APCI
      ionization.

PMID- 16417282
TI  - Near-infrared spectroscopy for measurement of total dietary fiber in homogenized
      meals.
AB  - Near-infrared (NIR) reflectance spectroscopy was investigated as a method for
      prediction of total dietary fiber (TDF) in mixed meals. Meals were prepared for
      spectral analysis by homogenization only (HO), homogenization and drying (HD),
      and homogenization, drying, and defatting (HDF). The NIR spectra (400-2498 nm)
      were obtained with a dispersive NIR spectrometer. Total dietary fiber was
      determined in HDF samples by an enzymatic-gravimetric assay (AOAC 991.43), and
      values were calculated for HD and HO samples. Using multivariate analysis
      software and optimum processing, partial least squares models (n = 114) were
      developed to relate NIR spectra to the corresponding TDF values. The HO, HD, and
      HDF models predicted TDF in independent validation samples (n = 37) with a
      standard error of performance of 0.93% (range 0.7-8.4%), 1.90% (range 2.2-18.9%),
      and 1.45% (range 2.8-23.3%) and r(2) values of 0.89, 0.92, and 0.97,
      respectively. Compared with traditional analysis of TDF in mixed meals, which
      takes 4 days, NIR spectroscopy provides a faster method for screening samples for
      TDF. The accuracy of prediction was greatest for the HDF model followed by the HD
      model.

PMID- 16417283
TI  - Noninvasive evaluation of the degree of ripeness in grape berries (vitis vinifera
      L. Cv. Bacchus and silvaner) by chlorophyll fluorescence.
AB  - The use of chlorophyll fluorescence measurements to noninvasively evaluate
      degrees of ripeness was investigated in berries at various stages of ripening
      from two white grapevine cultivars (Vitis vinifera L. Cv. Bacchus and Silvaner).
      Berries were characterized by diameter, weight, and density and by concentrations
      of fructose, glucose, sucrose, and total sugars, as well as fructose/glucose
      ratios, and also by chlorophyll fluorescence at F(0) and F(M) levels and the
      fluorescence ratio F(V)/F(M). Pearson product moment correlation analysis on data
      from both cultivars revealed clear negative associations between F(0) and
      concentrations of fructose, glucose, and total sugars, and fructose/glucose
      ratios (correlation coefficient < -0.89). Curvilinear trend-lines were
      established for plots of F(0) versus concentrations of fructose, glucose, and
      total sugars, but a linear relationship between F(0) and fructose/glucose ratios
      was found: the corresponding coefficients of determination were always >0.82.
      Therefore, chlorophyll fluorescence measurements are well-suited to determine
      noninvasively sugar accumulation in grape berries during ripening.

PMID- 16417284
TI  - Study on the antiinflammatory activity of methanol extract from seagrass Zostera
      japonica.
AB  - Methanolic extracts from the seagrass Zostera japonica were extracted
      successively using n-hexane (n-C(6)H(14)), dichloromethane (CH(2)Cl(2)), ethyl
      acetate (EtOAc), and water to give the n-C(6)H(14) (16.8%), CH(2)Cl(2) (40.6%),
      EtOAc (34.1%), and H(2)O (8.5%) soluble fractions, respectively. We have
      demonstrated that the hexane fraction has the highest capacity to inhibit proIL
      1beta expression as compared to other fractions in lipopolysaccharides (LPS)
      stimulated J774A.1 murine macrophages. Further analysis of the composition and
      antiinflammatory activity of the subfraction H5 from hexane fraction showed that
      it had the best antiinflammatory capacity and that it's major constituents were
      fatty acids, including palmitic acid methyl ester (21.5%), palmitic acid
      (24.02%), linoleic acid methyl ester (13.09%), oleic acid methyl ester (8.41%),
      and linoleic acid (7.93%), respectively. H5 inhibited LPS-induced TNFalpha, IL
      1beta, and IL-6 in a dose-dependent manner, suggesting that H5 is bioactive in
      antiinflammation in vitro. This study is the first to report the antiinflammatory
      activity of extracts obtained from the seagrass Z. japonica.

PMID- 16417285
TI  - Antioxidant polyphenols in almond and its coproducts.
AB  - Antioxidant efficacy of defatted almond whole seed, brown skin, and green shell
      cover extracts was evaluated by monitoring inhibition of human low-density
      lipoprotein (LDL) oxidation, inhibition of DNA scission, and metal ion chelation
      activities. The total phenolic contents of ethanolic extracts of brown skin and
      green shell cover of almond were 10 and 9 times higher than that of the whole
      seed, respectively. Brown skin extract at 50 ppm effectively inhibited copper
      induced oxidation of human LDL cholesterol compared to whole seed and green shell
      cover extracts, which reached the same level of efficacy at 200 ppm. Green shell
      cover extract at 50 ppm level completely arrested peroxyl radical-induced DNA
      scission, whereas 100 ppm of brown skin and whole seed extracts was required for
      similar efficiencies. All three almond extracts exhibited excellent metal ion
      chelation efficacies. High-performance liquid chromatographic (HPLC) analysis
      revealed the presence of quercetin, isorhamnetin, quercitrin, kaempferol 3-O
      rutinoside, isorhamnetin 3-O-glucoside, and morin as the major flavonoids in all
      extracts.

PMID- 16417286
TI  - Commercial dietary ingredients from Vitis vinifera L. leaves and grape skins:
      antioxidant and chemical characterization.
AB  - This paper reports an attempt to functionally and chemically characterize
      commercial ingredients from Vitis vinifera L. grape skins, grape pomace, and
      leaves, which are used in the formulation of dietary antioxidant supplements. The
      antioxidant capacity of these ingredients was assessed for the first time by the
      oxygen radical absorbance capacity (ORAC) methodology. Ingredients from grape
      skins and pomace (n = 17) showed ORAC values from 1.38 to 21.4 mumol Trolox
      equivalents/mg whereas ingredients from leaves (n = 4) showed ORAC values from
      1.52 to 2.55 mumol Trolox equivalents/mg. The high-performance liquid
      chromatography-diode array detection/electrospray ionization-mass sprectrometry
      analysis of anthocyanins and flavonols revealed the authenticity of the
      ingredients as derived from V. vinifera L. and confirmed large differences in
      their phenolic content and distribution. A progressive decline in both
      antioxidant capacity and total anthocyanin content of a grape skin ingredient (43
      and 40% decrease, respectively) was observed over a 60 day storage period (45
      degrees C and 75% relative humidity), demonstrating its poor stability under
      these conditions.

PMID- 16417287
TI  - The effect of temperature, photoperiod, and light quality on gluconasturtiin
      concentration in watercress (Nasturtium officinale R. Br.).
AB  - The effects of different growth regimes on gluconasturtiin concentration in
      watercress (Nasturtium officinale R. Br.) were investigated. Watercress plantlets
      at the 5th mature leaf stage (ca. 2 weeks old) were exposed to different day and
      night temperatures, to long (16 h) or short (8 h) days, to red (R) or far-red
      (FR) light given during the main long day photoperiod, and finally to R or FR
      light given at the end of the main photoperiod. Watercress plants grown under
      long days contained a 30-40% higher gluconasturtiin concentration and had a
      higher fresh weight than watercress plants grown under short days. Watercress
      plants grown under long days and temperatures of 15 or 10 degrees C had at least
      a 50% higher gluconasturtiin concentration, but a lower fresh weight, than that
      of plants grown at 20 or 25 degrees C. Watercress plants grown under metal halide
      light enriched with R light had approximately a 25-40% higher concentration of
      gluconasturtiin as compared to the FR-enriched plants. Likewise, a brief R light
      exposure at the end of the main photoperiod resulted in approximately a 25% or
      higher concentration of gluconasturtiin as compared to a FR end-of-day exposure.
      These data indicate that the concentration of gluconasturtiin in watercress can
      be significantly increased by growing plants at lower temperatures, under long
      days, and by exposure to R light.

PMID- 16417288
TI  - Lupane-type saponins from leaves of Acanthopanax sessiliflorus and their
      inhibitory activity on pancreatic lipase.
AB  - Three known saponins, chiisanoside, 11-deoxyisochiisanoside, and isochiisanoside,
      and one novel saponin, 3,4-seco-4(23),20(29)-lupadiene-3,28-dioic acid 28-O-alpha
      l-rhamnopyranosyl (1-->4)-beta-d-glucopyranosyl (1-->6)-beta-d-glucopyranoside,
      referred to as sessiloside, were isolated from a hot water extract of
      Acanthopanax sessiliflorus leaves. All of these saponins were lupane-type
      triterpene triglycosides, and their concentrations were 4.1, 1.0, 0.5, and 0.4%
      (w/w) of the total extract, respectively. Sessiloside and chiisanoside inhibited
      pancreatic lipase activity in vitro, and addition of the saponin-rich fraction to
      a high-fat diet suppressed the body weight gain of mice. The possibility of
      application of the lupane-type saponins from A. sessiliflorus leaves to the
      treatment of obesity is discussed.

PMID- 16417289
TI  - Antioxidant activity of a catechol derived from abietic acid.
AB  - The demand for novel effective antioxidant-based drugs has led to the synthesis
      and evaluation of the antioxidant potential in several molecules derived from
      natural compounds. In this work the in vitro antioxidant activity of an abietic
      acid-derived catechol (methyl 11,12-dihydroxyabietate-8,11,13-trien-18-oate,
      MDTO) was evaluated. This substance, possessing important biological properties,
      is similar to carnosic acid, a natural antioxidant from rosemary or sage leaves.
      Aiming to understand the antioxidant activity of MDTO, the energetics of its O-H
      bond, using time-resolved photoacoustic calorimetry (TR-PAC), was investigated.
      On energetic grounds it is predicted that MDTO is a good free radical scavenger,
      although its activity is lower than that of quercetin, a very effective
      antioxidant, which was used for comparison. In agreement with these predictions,
      the DPPH(*) and ABTS(*+) radical scavenging activities are lower than those of
      quercetin. In addition, MDTO also reacts with HOCl, a powerful proinflammatory
      oxidant produced by activated neutrophils, and protects liposomes against iron
      ascorbate-induced oxidation. The discussion of these results foresees potential
      applications of MDTO as an antioxidant.

PMID- 16417290
TI  - Thermoformed wheat gluten biopolymers.
AB  - The quantity of available wheat gluten exceeds the current food use markets.
      Thermoforming is an alternative technical means for transforming wheat gluten.
      Thermoforming was applied here to wheat gluten under chemically reductive
      conditions to form pliable, translucent sheets. A wide variety of conditions,
      i.e., temperature, reducing agents, plasticizers and additives were tested to
      obtain a range of elastic properties in the thermoformed sheets. These properties
      were compared to those of commercially available polymers, such as polypropylene.
      Elasticity of the gluten formulations were indexed by Young's modulus and were in
      the range measured for commercial products when tested in the 30-70% relative
      humidity range. Removal of the gliadin subfraction of gluten yielded polymers
      with higher Young's modulus since this component acts as a polymer-chain
      terminator. At relative humidity less than 30% all whole gluten-based sheets were
      brittle, while above 70% they were highly elastic.

PMID- 16417291
TI  - Native or raw starch digestion: a key step in energy efficient biorefining of
      grain.
AB  - Improved molecular disassembly and depolymerization of grain starch to glucose
      are key to reducing energy use in the bioconversion of glucose to chemicals,
      ingredients, and fuels. In fuel ethanol production, these biorefining steps use
      10-20% of the energy content of the fuel ethanol. The need to minimize energy use
      and to raise the net yield of energy can be met by replacing high-temperature,
      liquid-phase, enzymatic digestion with low temperature, solid-phase, enzymatic
      digestion. Also called cold hydrolysis, the approach is a step toward a "green"
      method for the production of fuel ethanol. There has been substantial prior and
      increased recent interest in this approach that is presented in this first review
      of the subject. We include incentives, developmental research, fundamental
      factors of raw starch digestion, and novel approaches in enzymology and
      processing. The discussion draws on resources found in enzymology, engineering,
      plant physiology, cereal chemistry, and kinetics.

PMID- 16417292
TI  - Physicochemical properties of natural phenolics from grapes and olive oil
      byproducts and their antioxidant activity in frozen horse mackerel fillets.
AB  - The reducing and chelating capacities and the affinity for the incorporation into
      the fish muscle of grape procyanidins, hydroxytyrosol, and propyl gallate were
      studied together with their antioxidant activity in frozen horse mackerel
      (Trauchurus trauchurus) fillets. Fillets were supplemented with phenolic
      antioxidants by (a) spraying an aqueous phenolic solution, (b) glazing with an
      aqueous phenolic solution, and (c) a previous washing of fillets with water plus
      spraying an aqueous phenolic solution. The effect of washing on the endogenous
      pro-oxidant/antioxidant balance of the fillets was also determined. All phenolic
      compounds were effective delaying lipid oxidation in the fish fillets. The order
      of antioxidant efficiency in spraying and glazing was propyl gallate >
      hydroxytyrosol > procyanidins, which was similar to the reducing power of these
      phenolics, but did not show any correlation with their chelating capacity and
      their affinity to the fish muscle. Washing the fillets with water prior to
      spraying phenols increased synergistically the antioxidant activity of grape
      procyanidins and changed the relative antioxidant efficiency to propyl gallate
      approximately procyanidins > hydroxytyrosol. This synergism may be a result of a
      better distribution of the procyanidins onto the fillet surface because of the
      residual water that remained on the fillets surface after washing.

PMID- 16417293
TI  - Chlorogenic acids and lactones in regular and water-decaffeinated arabica
      coffees.
AB  - The market for decaffeinated coffees has been increasingly expanding over the
      years. Caffeine extraction may result in losses of other compounds such as
      chlorogenic acids (CGA) and, consequently, their 1,5-gamma-quinolactones (CGL) in
      roasted coffee. These phenolic compounds are important for flavor formation as
      well as the health effects of coffee; therefore, losses due to decaffeination
      need to be investigated. The present study evaluates the impact of decaffeination
      processing on CGA and CGL levels of green and roasted arabica coffees.
      Decaffeination produced a 16% average increase in the levels of total CGA in
      green coffee (dry matter), along with a 237% increase in CGL direct precursors.
      Different degrees of roasting showed average increments of 5.5-18% in CGL levels
      of decaffeinated coffee, compared to regular, a change more consistent with
      observed levels of total CGA than with those of CGL direct precursors in green
      samples. On the other hand, CGA levels in roasted coffee were 3-9% lower in
      decaffeinated coffee compared to regular coffee. Although differences in CGA and
      CGL contents of regular and decaffeinated roasted coffees appear to be relatively
      small, they may be enough to affect flavor characteristics as well as the
      biopharmacological properties of the final beverage, suggesting the need for
      further study.

PMID- 16417294
TI  - Effect of high-pressure treatment and a bacteriocin-producing lactic culture on
      the odor and aroma of hispanico cheese: correlation of volatile compounds and
      sensory analysis.
AB  - The effect on the volatile compounds and on the odor and aroma of Hispanico
      cheese of a high-pressure (HP) treatment (400 MPa for 5 min at 10 degrees C,
      applied to 15-day-old cheeses), by itself or combined with the addition of a
      bacteriocin-producing (BP) culture to milk, was investigated. HP-treated cheeses
      showed higher levels of hexanal, 3-hydroxy-2-pentanone, 2-hydroxy-3-pentanone,
      and hexane and lower levels of ethanal, ethanol, 1-propanol, ethyl acetate, ethyl
      butanoate, ethyl hexanoate, 2-pentanone, and butanoic acid than untreated
      cheeses. HP cheeses received higher "milky" odor descriptor scores and lower
      scores for odor quality and intensity and for "buttery", "yogurt-like", and
      "caramel" odor descriptors. Addition of the BP culture enhanced the formation of
      three aldehydes, three alcohols, three ethyl esters, and three ketones but
      decreased the levels of seven ketones and butanoic acid. BP cheeses received
      higher scores for aroma intensity and for "yogurt-like" and "cheesy" aroma
      descriptors. Principal component analysis showed the correlation between
      diketones and aroma descriptors "caramel", "buttery", and "milky" and between 3
      methylbutanal and the odor and aroma intensity scores and aroma descriptors
      "sheepy" and "meat broth".

PMID- 16417295
TI  - Stability and color changes of thermally treated betanin, phyllocactin, and
      hylocerenin solutions.
AB  - Thermal degradation of betanin, phyllocactin (malonyl-betanin), and hylocerenin
      (3' '-hydroxy-3' '-methyl-glutaryl-betanin) solutions isolated from purple pitaya
      (Hylocereus polyrhizus [Weber] Britton and Rose) was monitored by
      spectrophotometric and high-performance liquid chromatography-diode array
      detection (HPLC-DAD) analyses. For betanin and phyllocactin solutions, the color
      shift upon thermal treatment was found to be nearly identical, while hylocerenin
      samples exhibited an intelligibly higher chromatic steadiness. Betanin proved to
      be the most stable individual pigment structure, while the enhanced tinctorial
      stability of the integral phyllocactin and especially hylocerenin solutions was
      due to the formation of red degradation products exhibiting improved color
      retention as opposed to their respective genuine pigments. Individual structure
      related stability characteristics can exclusively be assessed by HPLC-DAD
      analyses and may not be noticed by mere spectrophotometric assessment of color
      and tinctorial strength.

PMID- 16417296
TI  - Effect of far-infrared irradiation on catechins and nitrite scavenging activity
      of green tea.
AB  - The processed green tea leaves were irradiated by far-infrared (FIR) at eight
      temperatures (80, 90, 100, 110, 120, 130, 140, and 150 degrees C) for 10 min.
      After FIR irradiation, green teas were prepared by soaking the leaves in boiling
      water, and the physicochemical characteristics of the green tea were determined.
      FIR irradiation at 90 degrees C increased total phenol contents of green tea from
      244.7 to 368.5 mg/g and total flavanol contents from 122.0 to 178.7 mg/g,
      compared with non-irradiated control. FIR irradiation also significantly affected
      the amounts of epigallocatechin and epigallocatechin gallate. Nitrite scavenging
      activity also increased with increasing FIR irradiation until the temperature
      reached 110 degrees C. However, the overall color changes of green tea irradiated
      with FIR at 90 and 100 degrees C were negligible. These results indicate that the
      chemical quality of green tea is significantly affected by FIR irradiation
      temperature of the green tea leaves.

PMID- 16417297
TI  - Influence of fertilization on acrylamide formation during frying of potatoes
      harvested in 2003.
AB  - The quality of the potato has been found to vary, when grown under different
      agricultural and environmental conditions, such as the level of fertilization.
      Consequently these factors may influence the acrylamide formation during the
      preparation of French fries. These assumptions were studied on three varieties:
      Bintje, Ramos, and Saturna from the harvest of 2003. Decreasing N fertilization
      caused increases in the reducing sugar concentration from 60% up to 100% on DM
      for all varieties studied. Due to a high correlation between the reducing sugar
      content and the generation of acrylamide during frying, this resulted in a
      parallel increase in the acrylamide concentration of the French fries. Thus by
      lowering the amount of N fertilizer, an increase of 30-65% of the acrylamide
      generation during frying could be observed. It seems of extreme importance to
      find an appropriate balance between the level of N fertilizer in order to
      diminish acrylamide formation but on the other hand to obtain an acceptable tuber
      and to consider the environmental impact. All results reported should be seen in
      the perspective of the warm growing season of 2003.

PMID- 16417298
TI  - Oxygen deficiency in barley (Hordeum vulgare) grain during malting.
AB  - The steep water is generally aerated in industrial barley malting. However, it is
      questionable whether oxygen actually reaches the embryo, which remains entrapped
      under the husk, testa, and pericarp until chitting occurs. The aim of our study
      was to investigate whether barley embryos experience oxygen deficiency during
      steeping, and whether various steeping conditions affect the oxygen deficiency.
      Alcohol dehydrogenase Adh2 was induced in all steeping conditions studied.
      Therefore, oxygen deficiency occurred regardless of the steeping conditions.
      However, steeping conditions affected the rate of recovery from oxygen
      deficiency, germination rate, and onset of alpha-amylase production. When barley
      was subjected to oxygen deficiency by applying N(2) gas during steeping, the
      timing of the treatment determined its effects. The importance of aeration
      increased as the process proceeded. Oxygen deprivation at the beginning of the
      process had little effect on malt quality. Therefore, the timing of aeration is
      important in the optimization of germination during the steeping stage of
      malting.

PMID- 16417300
TI  - Genetic variation in pea seed globulin composition.
AB  - A quantitative characterization of seeds from 59 pea (Pisum sativum L.) lines and
      relative taxa with various external characteristics and wide geographical origin
      was performed to explore the genetic variation of pea concerning its starch and
      protein contents and globulin composition. Pea lines, which produce round,
      wrinkled, flat, and round-dimpled seeds, have starch as the major reserve, with
      an average content of 46%. Protein content varied from 13.7 to 30.7% of the seed
      dry matter, with an overall average of 22.3%. Densitometric quantification of the
      individual globulins (legumin, vicilin, convicilin, and globulin-related
      proteins) based on SDS-PAGE gels showed no lines lacking any particular globulin.
      Among the lines tested, variation was shown in both their total globulins content
      and their globulin composition. The total globulin content ranged from 49.2 to
      81.8% of the total pea protein extract (TPPE). Legumin content varied between 5.9
      and 24.5% of the TPPE. Vicilin was the most abundant protein of pea, and its
      content varied between 26.3 and 52.0% of the TPPE. Both processed and
      nonprocessed vicilins occurred. The processed vicilin was the predominant one,
      with values between 17.8 and 40.8%, whereas the nonprocessed ones constituted
      between 3.1 and 13.5% of the TPPE. Convicilin was the least abundant globulin,
      and its content ranged from 3.9 to 8.3%. Finally, the globulin-related proteins
      were present in amounts ranging from 2.8 to 17.3%. They were less abundant in
      comparison with legumin and vicilin, but they showed the largest relative
      variation of the four globulin classes. Correlations between the different
      external characteristics and globulin composition were determined. Comparison
      with soybean showed that pea lines show more variety in the abundance of globulin
      proteins, enabling a wider range of food application.

PMID- 16417299
TI  - Properties of low moisture composite materials consisting of oil droplets
      dispersed in a protein-carbohydrate-glycerol matrix: effect of continuous phase
      composition.
AB  - The influence of continuous phase composition on the properties of low moisture
      (<3% water) composite materials consisting of oil droplets dispersed in a protein
      carbohydrate-glycerol matrix was investigated. These composites were produced by
      blending canola oil (62.3%), whey protein concentrate (1.7%, WPC), and corn syrup
      and glycerol together (36.0% combined) using a high speed mixer equipped with a
      whisk. The polyol composition was varied by changing the ratio of corn syrup to
      glycerol in the system while keeping the total concentration of these two polyol
      components constant. Some composites were analyzed directly after preparation
      ("unbaked"), while others were analyzed after heating at 176 degrees C for 10 min
      to simulate baking of a food product ("baked"). The "lightness" of the composites
      was greater before baking (higher L value), but the color intensity of the
      composites was greater after baking (higher b value), which was attributed to
      Maillard browning reactions. The brownness of the baked composites increased with
      increasing corn syrup concentration, which was attributed to Maillard browning
      reactions. Squeezing flow viscometry indicated that the consistency and yield
      stress of the composites increased with baking, which was attributed to whey
      protein unfolding and aggregation. These rheological parameters also increased
      with increasing corn syrup concentration, which was attributed to its influence
      on the continuous phase rheology and on the interactions between the whey
      proteins. This study shows that the continuous phase composition and thermal
      history of low moisture composite materials have a large impact on their final
      physicochemical properties.

PMID- 16417301
TI  - Factors affecting the contents of iridoid oleuropein in olive leaves (Olea
      europaea L.).
AB  - In this study, for the first time, the impact of the genetic factor on the
      contents of oleuropein in olive leaves was not only evaluated but the influence
      exerted by the color/age of leaves (green, green-yellowish, and yellow) and the
      collecting period (spring or autumn) was also evaluated. A repetitive high
      resolution gas chromatographic quantitation method and an accurate high
      performance liquid chromatographic method were developed. These analytical
      methods gave results showing a highly linear relationship. Samples of olive
      leaves were taken from seven major Italian olive cultivars, such as Dritta,
      Leccino, Caroleo, Coratina, Castiglionese, Nebbio, and Grossa di Cassano. Such a
      vegetal raw material could actually be exploited for recovering oleuropein,
      considered to be a high-added value molecule. This could be converted into
      hydrxytyrosol, a compound known to possess strong bioactive properties. Olive
      leaves showed considerable contents of oleuropein, which with some cultivars were
      even higher with respect to those present in the corresponding olive fruits
      (reported in the literature). The amounts of oleuropein in the collected leaves
      were markedly modified by the color/age and genetic factors, whereas meaningless
      variations were ascribable to the quantitation method and the collecting period
      factors. Various chemometrics, applied to the obtained analytical data, appeared
      to be effective in discriminating the samples on the basis of the above-examined
      experimental factors, thus confirming how these should be taken into account in
      future industrial recovery of oleuropein from olive leaves.

PMID- 16417302
TI  - The influence of different electrical conductivity values in a simplified
      recirculating soilless system on inner and outer fruit quality characteristics of
      tomato.
AB  - Irrigation with saline water affects tomato fruit quality. While total fruit
      yield decreases with salinity, inner quality characterized by taste and health
      promoting compounds can be improved. For a detailed description of this
      relationship, the influence of three different salt levels [electrical
      conductivity (EC) 3, 6.5, and 10] in hydroponically grown tomatoes was
      investigated. Rising salinity levels in the nutrient solution significantly
      increased vitamin C, lycopene, and beta-carotene in fresh fruits up to 35%. The
      phenol concentration was tendentiously enhanced, and the antioxidative capacity
      of phenols and carotenoids increased on a fresh weight basis. Additionally, the
      higher EC values caused an increase of total soluble solids and organic acids,
      parameters determining the taste of tomatoes. Total fruit yield, single fruit
      weight, and firmness significantly decreased with rising EC levels. Regression
      analyses revealed significant correlations between the EC level and the dependent
      variables single fruit weight, total soluble solids, titrable acids, lycopene,
      and antioxidative capacities of carotenoids and phenols, whereas vitamin C and
      phenols correlated best with truss number, and beta-carotene correlated best with
      temperature. Only pressure firmness showed no correlation with any of the
      measured parameters. As all desirable characteristics in the freshly produced
      tomato increased when exposed to salinity, salinity itself constitutes an
      alternative method of quality improvement. Moreover, it can compensate for the
      loss of yield by the higher inner quality due to changing demands by the market
      and the consumer. This investigation is to our knowledge the first comprehensive
      overview regarding parameters of outer quality (yield and firmness), taste (total
      soluble solids and acids), nutritional value (vitamin C, carotenoids, and
      phenolics), as well as antioxidative capacity in tomatoes grown under saline
      conditions.

PMID- 16417303
TI  - Influence of Cultivar and Environmental Conditions on the Triacylglycerol Profile
      of Hazelnut (Corylus avellana L.).
AB  - The oil of several hazelnut (Corylus avellana L.) samples was extracted and
      evaluated for their triacylglycerol (TAG) composition. Trials were conducted in
      two Portuguese localities (Vila Real and Felgueiras) during three consecutive
      years and involved a total of 19 cultivars. The samples were analyzed by reversed
      phase high-performance liquid chromatography with evaporative light-scattering
      detection. Sample preparation was fast and simple, consisting only of the
      dissolution of the oil in acetone, homogenization, and filtration, allowing this
      technique to be suitable for routine analyses. All samples presented a similar
      qualitative profile composed of eleven compounds: LLL, OLL, PLL, OOL, POL, PPL,
      OOO, POO, PPO, SOO and PSO (P, palmitoyl; S, stearoyl; O, oleoyl; and L,
      linoleoyl). The main components were OOO, LOO, and POO, reflecting the high
      content of oleic acid in hazelnut oils. A total of 79 different samples were
      studied, and the obtained data were statistically analyzed. Significant
      differences were verified in canonical variate plots when cultivars were grouped
      by country of origin. In general, the American cultivars were richer in TAGs with
      saturated fatty acids moieties, and the group of French, German, and English
      cultivars was richer in TAGs containing linoleic acid moieties. Differences were
      also significant when cultivars were grouped by year of production, showing that
      besides genetic factors, the TAG composition can be influenced by environmental
      factors.

PMID- 16417304
TI  - Cutin composition of five finnish berries.
AB  - The raw cutin (i.e., extractive-free isolated cuticular membrane) fraction from
      Finnish berries, sea buckthorn (Hippophae rhamnoides), black currant (Ribes
      nigrum), cranberry (Vaccinium oxycoccos), lingonberry (Vaccinium vitis-idaea),
      and bilberry (Vaccinium myrtillus), was depolymerized by NaOMe-catalyzed
      methanolysis. The composition of cutin monomers was determined by GC-(EI)MS
      analysis either as methyl esters or as TMSi esters, with OH groups derivatized to
      TMSi ethers. There was a notable difference in the degree of depolymerization,
      ranging from 6 to 47%. The extractive-free berry cuticle, that is, raw cutin,
      thus contains <50% polyester polymer cutin. The predominant cutin monomers were
      C(16) and C(18) omega-hydroxy acids with midchain functionalities, mainly epoxy
      and hydroxyl groups. Typically, the major compounds were 9,10-epoxy-18
      hydroxyoctadecanoic acid, 10,16-dihydroxyhexadecanoic acid, 9,10,18
      trihydroxyoctadecanoic acid, 9,10-epoxy-18-hydroxyoctadec-12-enoic acid, and 18
      hydroxyoctadec-9-enoic acid. The amount of epoxyacids was rather high in sea
      buckthorn ( approximately 70%) and cranberry ( approximately 60%), compared with
      the other berries. The black currant cutin differed from that of the other
      berries with a significant portion of hydroxyoxohexadecanoic acid ( approximately
      12% of total monomers). This investigation of the cuticular hydroxy acids of five
      Finnish berries is part of the exploitation of the northern natural resources
      related to the chemical composition, nutritional value, and sensory properties.

PMID- 16417305
TI  - Vitamin k contents of meat, dairy, and fast food in the u.s. Diet.
AB  - The purpose of this study was to determine the contents of three forms of vitamin
      K [phylloquinone, dihydrophylloquinone, and menaquinone-4 (MK-4)] in
      representative samples (including different samples within the same food
      category) of meat (n = 128), dairy and eggs (n = 24), and fast foods (n = 169)
      common to the U.S. diet. The findings of our analysis indicate that no single
      food item in these categories is a rich dietary source of any one form of vitamin
      K. However, these foods are often consumed in large quantities; hence, they may
      be of importance in overall contribution to total vitamin K intake. The presence
      of MK-4 in meat, eggs, and dairy foods could be important as physiologic
      functions unique to MK-4 are identified.

PMID- 16417306
TI  - Fungicidal sesquiterpene dialdehyde cinnamates from Pseudowintera axillaris.
AB  - Bioactivity-directed separation of a foliage extract from the New Zealand shrub
      Pseudowintera axillaris led to a compound with fungicidal activity against the
      plant pathogen Phytophthora infestans. This was identified as a new sesquiterpene
      dialdehyde cinnamate named paxidal. Two 6-hydroxy derivatives were present at
      lower levels in the extract. A further nine derivatives were synthesized from
      these natural products for a structure-activity study against a range of
      important food crop pathogens. The cinnamate group was important for fungicidal
      effects, and protection of the dialdehyde as a dimethyl acetal gave more potent,
      broader spectrum activity.

PMID- 16417307
TI  - Photodegradation of fenitrothion and parathion in tomato epicuticular waxes.
AB  - Photodegradation of (14)C-labeled fenitrothion ([O,O-dimethyl O-(3-methyl-4
      nitrophenyl) phosphorothioate]) and parathion ([O,O-diethyl O-(4-nitrophenyl)
      phosphorothioate]) was conducted on a series of solid surfaces including isolated
      tomato fruit and leaf cuticle waxes. The wax-coated glass plate gave the
      comparative degradation of fenitrothion observed for the intact plant but both
      surfaces of octadecyl-capped silica gel and poly(tetrafluoroethylene) enhanced
      its volatilization. Photoinduced desulfuration and ester cleavage were common to
      both pesticides in waxes, but formation of the azo derivative was found to be a
      major degradation pathway characteristic of parathion. The modified electronic
      states of the nitro group by introduction of m-methyl group accounted for this
      different photoreactivity based on molecular orbital calculations.

PMID- 16417308
TI  - Use of a complexation of tebuconazole with beta-cyclodextrin for controlling foot
      and crown rot of durum wheat incited by Fusarium culmorum.
AB  - The methodology for the inclusion of tebuconazole (TBC) in beta-cyclodextrin
      (betaCD), spectroscopic characterization of the inclusion complex, and its
      activity for the control of a major soilborne disease of wheat caused by Fusarium
      culmorum are reported. Controlled release measured by chemical shift of the
      diagnostic protons H(3) and H(5) of betaCD confirmed stability of the complex at
      the solid state and in aqueous solution. Greenhouse and field experiments were
      conducted on durum wheat (Triticum durum cv. Prometeo) sown in substrate or in
      soil artificially infested with a virulent strain of F. culmorum. The inclusion
      complex betaCD-TBC, applied as seed dressing in combination or not with
      carboxymethylcellulose, reduced the disease incidence caused by F. culmorum and
      improved grain yield, showing effects that were generally comparable to those
      observed upon application of a commercial formulation of TBC. In the field
      experiment, only seed treatment with the inclusion complex betaCD-TBC allowed
      yield that was not different from that obtained from the uninoculated control.
      These results prove that by the use of the betaCD-TBC complex it is possible to
      obtain release of TBC and bioavailabilty of the fungicide without compromising
      its effectiveness.

PMID- 16417309
TI  - Characterization of cachaca and rum aroma.
AB  - Cachaca, the most popular alcoholic beverage in Brazil, is a sugar cane spirit
      similar to rum. Its production is around 2 billion liters per year, of which <1%
      is exported. Although rum is similar to cachaca its flavor difference is easily
      recognizable. Using gas chromatography-olfactometry (GCO) to separate and
      characterize the odorants present in cachaca and rum, these two sugar cane
      products were compared and standards identified to use in a descriptive sensory
      analysis (DSA). In the DSA cachaca was more intense in the grassy, spicy,
      sulfury, and vinegar descriptors, whereas apple and caramel were the same in both
      rum and cachaca. The GCO data for the apple-smelling compounds beta-damascenone
      along with ethyl butyrate, isobutyrate, and 2-methylbutyrate were at the same
      potency in both cachaca and rum, whereas the spicy-smelling eugenol, 4
      ethylguaiacol, and 2,4-nonadienal were much more potent in cachaca.

PMID- 16417311
TI  - Identification of components responsible for the odor of cigar smoker's breath.
AB  - Following smoking 1/2 of a cigar, the most odorous cigar tobacco smoke components
      extracted from the surface of the tongue by nylon-meshed swabs and then extracted
      from the swab headspace by solid phase microextraction were ethyl pyrrole, 2,3
      dimethyl pyrazine, and 2-ethyl pyridine. Similar classes of compounds were
      identified from the headspace of an aqueous simulated saliva solution treated
      with cigar smoke. The most odorous compounds were 2,3,5-trimethyl pyridine, 2,5
      dimethyl pyrazine, and 2-ethyl-3,5-dimethyl pyridine. Pyridines and pyrazines,
      the most prominent classes of odorous compounds identified in this experiment,
      may be generated during cigar pyrrolysis by cleavage of nicotine or by Maillard
      reaction.

PMID- 16417310
TI  - Intensity and persistence profiles of flavor compounds in synthetic solutions.
      Simple model for explaining the intensity and persistence of their aftersmell.
AB  - Hydroalcoholic solutions containing a single aroma-active compound were evaluated
      by a sensory panel to determine the difference between ortho and retronasal odor
      intensities (DeltaI(ro)), buccal savoring, and aftersmell duration. Eight
      compounds were used. Buccal perception seems to be just a physiologically
      restricted form of retronasal perception. DeltaI(ro) values were dependent on the
      panel, although results from the two panels were significantly correlated. Such
      differences and the aftersmell persistence were also significantly correlated
      with different physicochemical parameters related to volatility. A simple model
      to explain such dependence is proposed. The model considers the mouth-throat
      system as a perfect mixing tank with a finite amount of odorants being
      progressively diluted by swallowing and purging (both taken as continuous
      processes). Retronasal intensity is modeled from the odor properties of the
      liquid in such a tank calculated from orthonasal odor intensity versus
      concentration (I/log C) curves. The model explains successfully experimental
      results and has also been successfully applied to instrumental data from other
      authors.

PMID- 16417312
TI  - Reduction of stale flavor development in low-heat skim milk powder via
      epicatechin addition.
AB  - The influence of epicatechin (EC) on off-flavor development in low-heat skim milk
      powder samples during processing and storage was investigated. Milk powder
      samples were prepared from a concentrated skim milk (control) plus a concentrated
      skim milk with EC (treatment). Volatile extracts of the powders were analyzed by
      aroma extract dilution analysis (AEDA) at 0 days and after 17 months of storage
      in conjunction with sensory analysis of the flavor attributes. The treatment milk
      powders with EC added prior to drying reported a reduction in the formation of
      three main compounds, 4-hydroxy-2,5-dimethyl-3-(2H)-furanone, o
      aminoacetophenone, and furfural, by 8-, 4-, and 4-fold for the 0 day old samples,
      while for the 17 month aged samples o-aminoacetophenone was the major compound
      reduced in formation by 8-fold, respectively, based on the flavor dilution
      factors reported. The sensory evaluations indicated that the treatment milk
      powders for 0 day old and 17 month aged samples were statistically lower (alpha =
      0.05) in stale flavor intensity in comparison to the respective control samples,
      while no differences were noted in bitterness intensity.

PMID- 16417313
TI  - Characterization of odor-active volatiles in champa (Campomanesia lineatifolia R.
      and P.).
AB  - Volatile extracts from pulp, peels, leaves, and seeds of champa (Campomanesia
      lineatifolia R. and P.) were obtained by continuous liquid-liquid extraction with
      pentane/dichloromethane (1:1), and their chemical composition was determined by
      using HRGC and HRGC-MS. Differences between C. lineatifolia volatile extracts
      with regard to the identified compounds are presented; however, in all of them
      the beta-triketones were detected as major constituents (between 50 and 60% of
      total extract). An odor profile description of volatiles isolated in all of the
      extracts was obtained by HRGC-O. These analyses showed that beta-triketones
      contributed to the fruity, floral, and green odor notes in the flavor of fruit.
      Application of AEDA to pulp volatile extract revealed 2,5-dimethyl-4-methoxy
      3(2H)-furanone, 2-phenylethanol, and 2,3-dihydro-5-hydroxy-6,8,8-trimethyl-2
      phenyl-4H-1-benzopyran-4,7(8H)-dione (champanone C) to have the highest flavor
      dilution factors. In a similar way, (E)-cinnamyl alcohol, 2,5-dimethyl-4-methoxy
      3(2H)-furanone, and 2,3-dihydro-5-hydroxy-6,8,8-trimethyl-2-phenyl-4H-1
      benzopyran-4,7(8H)-dione (champanone C) were identified as key odorant compounds
      in the fruit peel volatile extract. This is the first time that the volatile
      composition in champa is reported and also the sensory odor importance of beta
      triketones.

PMID- 16417314
TI  - Zein dynamic adsorption to carboxylic and alkyl coated surfaces.
AB  - The adsorption of a commercial zein sample on carboxylic (COOH) and alkyl (CH(3))
      surfaces was monitored by high time resolution surface plasmon resonance. Zein
      showed higher affinity and higher mass adsorption on carboxylic than alkyl
      surfaces. A zein layer specific for each surface was obtained after flushing off
      loosely bound zein with 75% 2-propanol solutions. Zein deposits were examined
      under atomic force microscopy. Differences in layer thickness between carboxylic
      and alkyl surfaces were explained in terms of zein adsorption footprint.

PMID- 16417315
TI  - Starch properties of mutant rice high in resistant starch.
AB  - As the staple food of over half the world's population, hot cooked rice high in
      resistant starch (RS) is of particular interest, which will have greater impact
      in the dietary prevention of diabetes and hyperlipidemia. A mutant rice high in
      RS in hot cooked rice, described as RS111, was comparatively studied with the
      wild type and common rice. Despite obviously low RS content in the raw milled
      rice, the RS content in the hot cooked rice of mutant RS111 was significantly
      higher than that of the wild type and common rice and, correspondingly, in vitro
      starch hydrolysis by porcine pancreatic alpha-amylase tends to be incomplete with
      low hydrolysis extent for the cooked mutant rice high in RS. Obvious differences
      in physicochemical properties, starch granule morphology, pasting properties,
      thermal properties, and X-ray diffraction pattern were observed among the mutant
      RS111, wild type, and common indica rice. The high-RS mutant was characterized by
      significantly higher apparent amylose content and crude lipid content, higher
      percentage of oval-shaped granules and bigger oval size, reduced paste viscosity,
      and low onset temperature, peak temperature, final temperature, enthalpy of
      gelatinization, and crystallinity.

PMID- 16417316
TI  - Influence of crystallization on the oxidative stability of extra virgin olive
      oil.
AB  - The aim of this study was to evaluate the influence of the extra virgin olive oil
      (EVOO) physical state on the kinetics of oxidative reactions. To this purpose,
      EVOO was stored at increasing temperatures from 3 to 60 degrees C and the
      oxidation was followed by measuring both primary and secondary oxidation
      products. Results highlighted that crystallization plays an important role in
      determining EVOO stability. Below the melting point, the oxidation rate was found
      to be higher than that expected on the basis of the Arrhenius equation. The
      observed deviation from the Arrhenius equation was attributed to the
      physicochemical changes occurring as a consequence of phase transitions. In
      particular, the increase in unsaturated triacylglycerol concentration and the
      decrease of polyphenol content in the liquid phase surrounding fat crystals were
      indicated as the main factors causing the deviation. By taking into account these
      changes it was possible to describe the temperature dependence of the oxidation
      rate in the entire range of temperatures considered. This model appears to be
      promising in the challenge to find mathematical models able to predict the
      stability and, hence, the shelf life of lipid-containing foods.

PMID- 16417317
TI  - New flavanol-anthocyanin condensed pigments and anthocyanin composition in
      guatemalan beans (Phaseolus spp.).
AB  - It has long been considered that the pigments resulting from direct condensation
      between anthocyanins and flavanols were formed exclusively during storage and
      processing, both in plant-derived foods and in drinks. Recently, however, the
      minor presence of this type of pigment has been shown in different plant
      extracts, among them beans. In this work we have studied this family of pigments
      in beans from Guatemala belonging to two distinct species of the genus Phaseolus,
      confirming the presence of (epi)gallocatechin carbon-carbon linked to the
      aglycone of delphinidin and (epi)catechin-cyanidin-3-glucoside. Furthermore, for
      the first time in this foodstuff another three flavanol-anthocyanin condensed
      pigments formed by the linkage of (epi)catechin with the corresponding aglycones
      of cyanidin, petunidin, and peonidin have been described. Also, the natural
      occurrence of anthocyanidins in this matrix has been confirmed in some of the
      samples analyzed in this work, the majority being components of their anthocyanin
      composition. The corresponding aglycones of delphinidin, cyanidin, petunidin,
      pelargonidin, and malvidin have been identified as well as two aglycones with
      identical mass to those of peonidin and petunidin, but with different retention
      times, which leads to the supposition that they are probably methylated
      derivatives of cyanidin and delphinidin, respectively.

PMID- 16417318
TI  - Structural characterization of alpha-zein.
AB  - A variety of published physical measurements, computational algorithms, and
      structural modeling methods have been used to create a molecular model of 19 kDa
      alpha-zein (Z19). Zetaeins are water-insoluble storage proteins found in corn
      protein bodies. Analyses of the protein sequence using probability algorithms,
      structural studies by circular dichroism, infrared spectroscopy, small-angle X
      ray scattering (SAXS), light scattering, proton exchange, NMR, and optical
      rotatory dispersion experiments suggest that Z19 has approximately 35-60% helical
      character, made up of nine helical segments of about 20 amino acids with
      glutamine-rich "turns" or "loops". SAXS and light-scattering experiments suggest
      that in alcohol/water mixtures alpha-zein exists as an oblong structure with an
      axial ratio of approximately 6:1. Furthermore, ultracentifugation, birefringence,
      dielectric, and viscosity studies indicate that alpha-zein behaves as an
      asymmetric particle with an axial ratio of from 7:1 to 28:1. Published models of
      alpha-zein to date have not been consistent with the experimental data, and for
      this reason the structure was re-examined using molecular mechanics and dynamics
      simulations creating a new three-dimensional (3D) structure for Z19. From the
      amino acid sequence and probability algorithms this analysis suggested that alpha
      zein has coiled-coil tendencies resulting in alpha-helices with about four
      residues per turn in the central helical sections with the nonpolar residue side
      chains forming a hydrophobic face inside a triple superhelix. The nine helical
      segments of the 19 kDa protein were modeled into three sets of three interacting
      coiled-coil helices with segments positioned end to end. The resulting structure
      lengthens with the addition of the N- and C-terminal sections, to give an axial
      ratio of approximately 6 or 7:1 in agreement with recent experiments. The natural
      carotenoid, lutein, is found to fit into the core of the triple-helical segments
      and help stabilize the configuration. Molecular dynamics simulations with
      explicit methanol/water molecules as solvent have been carried out to refine the
      3D structure.

PMID- 16417319
TI  - Effect of lectins on the transport of food factors in caco-2 cell monolayers.
AB  - The effect of three plant lectins, soybean lectin (SBA), Japanese jack bean
      lectin (CGA), and wheat germ lectin (WGA), on the transport of various food
      factors, such as isoflavones, quercetin, dipeptides, and calcium ions, were
      investigated by use of an intestinal tract model, Caco-2 cell monolayers. The
      lectins increased the isoflavone transport but had no effect on aglycon
      transport. SBA increased the transport of quercetin glycosides, whereas CGA and
      WGA had no effect. The lectins increased the transport of calcium ions but showed
      no effect on the transport of dipeptides, carnosine, and anserine. Although SBA
      did not change the transepithelial electrical resistance (TER) value of the Caco
      2 cell monolayers, CGA and WGA decreased the TER value. These results indicate
      that plant lectins affect the transport of food factors in different manners,
      presumably due to their specific sugar binding activity.

PMID- 16417320
TI  - Study of thermal aggregation of globulin from common buckwheat (Fagopyrum
      esculentum Moench) by size-exclusion chromatography and laser light scattering.
AB  - The heat-induced aggregation of common buckwheat (Fagopyrum esculetum Moench)
      globulin (BWG) was studied using size-exclusion chromatography (SEC) combined
      with on-line multiangle laser light scattering (MALLS) and quasielastic light
      scattering (QELS). The unheated BWG was found to exist mainly as a hexamer, with
      an estimated weight-average molecular weight (M(w)) of 342 000, close to that
      deduced from the genomic cloned data of 13S buckwheat globulin. The QELS data
      predicted that the hexamer exists as two annular trimeric rings (diameter
      approximately 10.8 nm) placed on top of each other, forming an oblate cylinder
      (height approximately 9.1 nm). Upon heating, hexamers and trimers were
      dissociated and then associated to form extended small aggregates, finally
      forming compact, large macroaggregates. N-Ethylmaleimide would favor
      macroaggregate formation and increased the molar masses and hydrodynamic radii of
      the soluble aggregates, suggesting a different aggregation process in the
      presence of the sulfhydryl-blocking agent. A plot of log hydrodynamic radius
      versus log molar mass showed changes in the slope during heat treatment,
      suggesting conformational transformation in the heat-denatured and aggregated BWG
      molecules.

PMID- 16417321
TI  - Purification and characterization of novel proteinase inhibitors from dried figs.
AB  - Two types of the natural organic matter P and B were isolated from dried figs by
      gel permeation and high-performance liquid chromatography. The characterizations
      of their molecular structures were also performed using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and infrared absorption
      spectrometry. As a result, these samples were revealed to inhibit the serine and
      cysteine proteinases chymotrypsin and papain (K(i) = 10(-)(6)-10(-)(4) M). The
      optimal inhibitory pH values of the P and B samples were observed to be
      approximately 5.5 and 5.0, respectively. The analyses of their UV-vis absorption
      spectra and infrared absorption spectra indicated that they would be a kind of
      humic substance. The mass spectrometry analyses showed that they possessed
      relatively small heterogeneous molecules with molecular masses around 692, 845,
      and 1389 Da for the P sample and around 551, 704, and 909 Da for the B sample.

PMID- 16417323
TI  - Role of the solvent glycerol in the Maillard reaction of d-fructose and l
      alanine.
AB  - The volatiles in the headspace above a solution of [(13)C(6)]fructose and alanine
      in glycerol/water, heated in a closed vial at 130 degrees C for 2 h, were
      analyzed by solid-phase microextraction in tandem with GC-MS. Carbonyl compounds
      and pyrazines were among the detected components. The examination of their mass
      spectra showed that most of the 1-hydroxy-2-propanone and 2,3-pentanedione were
      (13)C(3)-labeled, the majority of the 2-methylpyrazine and 2-ethyl-3
      methylpyrazine were (13)C(5)-labeled, and 2,5-dimethylpyrazine and 3-ethyl-2,5
      dimethylpyrazine were mainly (13)C(6)-labeled. This is in agreement with the
      literature, and corresponds to the incorporation of fructose carbons, and in the
      case of 2,3-pentanedione, 2-ethyl-3-methylpyrazine, and 3-ethyl-2,5
      dimethylpyrazine alanine carbons, into the molecules. However, minority fractions
      of 1-hydroxy-2-propanone (10%) and 2,3-pentanedione (14%) were found unlabeled, 2
      methylpyrazine (10%) and 2-ethyl-3-methylpyrazine (11%) only doubly labeled, and
      2,5-dimethylpyrazine (20%) and 3-ethyl-2,5-dimethylpyrazine (27%) only triply
      labeled, suggesting they contain carbons originating from the solvent glycerol.
      This could be confirmed by reaction of fructose and alanine in
      [(13)C(3)]glycerol/water, which produced the same volatiles, with 11-27% existent
      in their (13)C(3)-labeled form. Hence, glycerol participated not only as a
      solvent but also as a precursor in the reaction.

PMID- 16417322
TI  - Incorporation of alpha-tocopherol and linoleic acid in fresh lambs by feeding
      chemically treated dietary supplements containing dl-alpha-tocopheryl acetate and
      sunflower oil.
AB  - The effects of feeding chemically treated dietary supplements (CTDS) containing
      sunflower oil and dl-alpha-tocopheryl acetate (TA) on alpha-tocopherol content
      and fatty acid profile in edible tissues of lambs were estimated. Compared with
      lambs fed control diet (CD), lambs fed CD plus 250 IU of either TA or CTDS
      increased serum alpha-tocopherol. The CTDS-fed lambs further increased serum
      alpha-tocopherol by 29% over those fed CD plus 250 IU of TA. Lambs supplemented
      with TA or CTDS increased alpha-tocopherol in muscle and adipose tissues as
      compared with lambs fed CD. The CTDS-fed lambs had higher levels of alpha
      tocopherol in gluteus medius (7.55 vs 6.05 mug/g), psoas major (7.43 vs 6.02
      mug/g), and subcutaneous fat (12.6 vs 9.98 mug/g) compared with the TA-fed lambs.
      Feeding lambs CTDS also substantially increased levels of linoleic acid in the
      adipose tissues while decreasing the content of palmitic and oleic acids.

PMID- 16417324
TI  - Ingested delphinidin-3-rutinoside is primarily excreted to urine as the intact
      form and to bile as the methylated form in rats.
AB  - Many reports have described the bioavailability of anthocyanins; however, most of
      these reports investigated only the amount of anthocyanins excreted in urine. In
      the present study, we calculated the pharmacokinetic bioavailability of
      anthocyanins in rats by measuring the plasma concentration of delphinidin-3
      rutinoside that had been administered orally or intravenously. Delphinidin-3
      rutinoside was primarily absorbed in the blood and excreted into urine as
      unmetabolized forms with a T(max) of 26.3 min and a C(max) of 0.285 +/- 0.071
      micromol/L. We detected small amounts of the metabolite 4'-O-methyl-delphinidin-3
      rutinoside in the plasma, but we detected neither anthocyanidin (aglycone) nor
      glucuro- or sulfoconjugates. For the 8 h period after intake, delphinidin-3
      rutinoside and 4'-O-methyl-delphinidin-3-rutinoside were excreted to urine at 795
      +/- 375 and 12.3 +/- 2.91 nmol, respectively. Relative to intravenous injection,
      oral administration of delphinidin-3-rutinoside resulted in complete
      bioavailability (0.49 +/- 0.06%). Analysis of delphinidin-3-rutinoside plasma
      concentrations in bile cannulated rats revealed that, for the 8-h period after
      intake, the intact delphinidin-3-rutinoside excretion ratio in bile was 11% of
      the excretion ratio of 4'-O-methyl-delphinidin-3-rutinoside, 1.91 +/- 0.35 nmol
      versus 17.4 +/- 8.67 nmol, respectively. Setting the bile duct cannulation in a
      Bollman-type cage, however, significantly increased the bioavailability of orally
      administered delphinidin-3-rutinoside (18.14 +/- 6.24%). This effect appears to
      stem immobilization stress by reducing gastrointestinal motility. The cumulative
      excretion of delphinidin-3-rutinoside and 4'-O-methyl-delphinidin-3-rutinoside in
      urine and bile was 2.67 +/- 1.24% (w/w) of the dose ingested. Studies report that
      several metabolites are formed after oral ingestion of anthocyanins. Examples
      include glucuronyl from cyanidin-3-glucoside and both glucuronyl and sulfate
      conjugates from pelargonidin-3-glucoside. Our results indicate that delphinidin-3
      rutinoside might be metabolized differently from cyanidin-3-glucoside and
      pelargonidin-3-glucoside.

PMID- 16417325
TI  - Fate of anthocyanins and antioxidant capacity in contents of the gastrointestinal
      tract of weanling pigs following black raspberry consumption.
AB  - Many fruits are rich in anthocyanins (ACNs). ACNs have high antioxidant capacity,
      but because of their apparent low bioavailability, their possible roles in health
      promotion in vivo are still in question. The objectives of these studies were to
      determine the fate of ACNs within the gastrointestinal (GI) tract and the effect
      on the bioavailability and subsequent metabolism of ACNs. Five weanling pigs were
      fed freeze-dried black raspberry (Rubus occidentalis L.) powder by oral
      administration, which provided 1146.1 +/- 44.6 micromol TE of oxygen radical
      absorbance capacity with fluorescein as a fluorescent probe (ORAC(FL)) per kg and
      50.5 +/- 3.7 mg per kg total ACNs. After 4 h, the pigs were sacrificed and the
      contents of five GI segments (duodenum, jejunum, ileum, cecum, and colon) were
      collected and analyzed for their total antioxidant capacity (TAC, measured as
      ORAC(FL)) and ACNs. The recoveries of TAC and total ACNs were 46.5 +/- 3.5 and
      41.7 +/- 4.9%, respectively. Both total ACNs and TAC were recovered primarily in
      the ileum, cecum, and colon at 4 h after a meal. Cyanidin aglycone with different
      sugar moieties showed significant differences in their recovery within the GI
      tract with sambubiose > sambubiose-rhamnose = rutinose >> glucose. Recovery of
      ACNs within the GI tract was positively and linearly associated with urinary ACN
      recovery, which suggests that stability within the GI tract and not decreased
      absorption accounts for the increased recovery. The environment of different
      segments of the GI tract may determine the stability of individual ACNs. Complex
      ACNs containing di- or triglycosides disappeared more slowly in the GI tract than
      simple ACNs such as a monoglycoside. TAC and total ACNs remained high 4 h after
      feeding, which indicates that ACNs provide significant antioxidant protection in
      the environment of the gut epithelium.

PMID- 16417326
TI  - Enzymatic and mechanistic studies on the formation of N-phenylglycolohydroxamic
      acid from nitrosobenzene and pyruvate in spinach leaf homogenate.
AB  - The biotransformation mechanism of an unknown metabolite formed enzymatically
      from nitrosobenzene (NOB) and pyruvate in spinach (Spinacea oleracea L.) was
      investigated using spinach leaf homogenate. The unknown metabolite was identified
      as N-phenylglycolohydroxamic acid (PGA). The activity of PGA formation was
      decreased by l-alanine, increased by l-serine, and completely inhibited by
      aminooxyacetic acid, an inhibitor of transaminases. These results indicate that
      the transaminase participates in PGA formation. Indeed, hydroxypyruvate and
      alanine were produced in the transamination between pyruvate and serine.
      Hydroxypyruvate served as a direct-acting glycoloyl donor for PGA formation. A
      good correlation between the activities of the 200 g supernatant of spinach
      homogenate and commercial yeast transketolase for PGA formation from several
      glycoloyl donors was obtained. These results suggest the following mechanism for
      PGA formation from NOB and pyruvate: transamination of l-serine into
      hydroxypyruvate, which serves as a glycoloyl donor to NOB.

PMID- 16417327
TI  - Dehydration in the folding of reduced cytochrome c revealed by the electron
      transfer-triggered folding under high pressure.
AB  - We determined the activation volume associated with protein folding of reduced
      cytochrome c from the collapsed intermediate to the native state. The folding
      rate was followed by a change in the absorption (420 nm) at various pressures
      between 0.1 and 200 MPa and at various concentrations of denaturant (guanidine
      hydrochloride) between 3.2 and 4.0 M. Dependence of the folding rate on both
      these factors revealed that the activation volume at ambient pressure in the
      absence of denaturant is negative (DeltaVf0 = -14 (+/-8) cm3.mol-1). Such a
      negative activation volume can be accounted for by a decrease in volume resulting
      from the dehydration of hydrophobic groups, primarily the heme group.
      Dehydration, which increases the entropy of the protein system, compensates for a
      decrease in the entropy accompanying the formation of the more compact and
      ordered transition state. We, therefore, propose that the positive change in the
      activation entropy for the folding reaction is due to the dehydration of
      hydrophobic groups. Furthermore, dehydration entropically promotes the protein
      folding reaction.

PMID- 16417328
TI  - Folding and unfolding of chromophoric foldamers show unusual colorful single
      molecule spectral dynamics.
AB  - A series of well-defined linear multichromophoric foldamers with a specific
      sequence of alternating rigid perylene chromophores and flexible ethylene glycol
      chains were studied by single molecule fluorescence spectroscopy. Monomer showed
      minor spectral fluctuations compared to trimer and hexamer, which showed unusual
      and colorful spectral dynamics attributed to a stochastic photoinduced
      unfolding/folding phenomenon. The range of spectral shapes observed indicates
      varying degrees of pi-pi interaction between adjacent chromophores, with
      vibronically resolved green emission indicating completely unfolded structures
      and broad red emission indicating highly coupled and extensively folded pi
      stacks. The rate of switching between different spectral shapes in the spectral
      trajectories suggests the existence of multiple pathways between the folded and
      unfolded states.

PMID- 16417329
TI  - Solvent-tuned azido-bridged Co2+ layers: square, honeycomb, and Kagome.
AB  - Three azido-bridged Co2+ complexes with square, honeycomb, and Kagome layered
      structures were synthesized and structurally characterized. Crystallization
      solvents are found to be critical in generating the observed topologies. These
      structurally related complexes are of significance in studying two-dimensional
      antiferromagnetism and geometric frustration.

PMID- 16417330
TI  - Fabrication of antibody arrays using thermally responsive elastin fusion
      proteins.
AB  - A general method has been developed to immobilize antibodies onto an array
      surface by employing fusion proteins consisting of an elastin domain with tunable
      hydrophobic properties and an antibody-binding domain with high binding affinity
      and specificity for antibodies. Antibodies conjugated with the elastin fusion
      proteins can be directly printed on a self-assembled monolayer-modified glass
      slide in a functionally active orientation with a spatially defined pattern. An
      antibody array sensor for detection of tumor markers was fabricated to
      demonstrate the utility of the method. We expect that the method presented here
      could be a simple and universal platform to immobilize antibodies for the
      fabrication of a variety of antibody array sensors.

PMID- 16417332
TI  - Efficient intramolecular energy transfer in single endcapped conjugated polymer
      molecules in the absence of appreciable spectral overlap.
AB  - Intramolecular energy transfer is investigated in an endcapped conjugated polymer
      on the single molecule level at low temperature. While light harvesting in one
      dimension is on average inefficient in the ensemble, the efficiency scatters
      widely on the single molecule level, with some molecules exhibiting near-unity
      transfer probability from the polymer backbone donor to the acceptor endcap. This
      transfer occurs in the absence of spectral overlap between donor and acceptor, as
      the electronic and vibronic transitions narrow substantially at low temperatures
      once inhomogeneous disorder broadening is overcome. The results illustrate how
      far-field absorption and emission characteristics of molecular transitions are
      insufficient to describe resonant energy transfer processes following Forster
      theory in multichromophoric aggregates. Rather, exciton trapping due to efficient
      multiphonon emission has to be invoked with a possible contribution of strong
      polaronic coupling.

PMID- 16417331
TI  - NMR imino proton exchange experiments on duplex DNA primarily monitor the opening
      of purine bases.
AB  - Molecular dynamics simulations were performed to investigate GC and AT base
      opening events in DNA. Calculated equilibrium constants between the base open (or
      flipped) and closed states were shown to be in good agreement with experimental
      data from NMR imino proton exchange experiments. Analysis of the computed results
      indicates that the equilbrium constants are dominated by the opening of the A and
      G bases in the AT and GC base pairs, respectively. Thus, the present results
      predict that NMR imino proton exchange experiments of base opening are primarily
      monitoring the opening of purine bases.

PMID- 16417333
TI  - Gluing Langmuir-Blodgett monolayers onto hydrocarbon surfaces.
AB  - This paper describes a new approach for modifying hydrophobic surfaces that is
      based on the use of ionically cross-linked (i.e., "glued") Langmuir-Blodgett
      monolayers. Specifically, this work shows how monolayers of 5,11,17,23,29,35
      hexa(trimethylammonium methyl)-37,38,39,40,41,42-hexakis-n-hexadecyloxy
      calix[6]arene (1a), which have been ionically cross-linked with poly(4-styrene
      sulfonate) (PSS, MW 30,000-50,000), can be deposited onto silylated silicon
      wafers with their polar headgroups extending outward into air. This work also
      demonstrates the feasibility of using glued monolayers of 1a as "anchors" for
      attaching alternating layers of poly(diallyldimethylammonium) [PDADMA] and PSS
      ions onto these same hydrocarbon surfaces.

PMID- 16417334
TI  - Photoresponsive multilayer spiral nanotubes: intercalation of polyfluorinated
      cationic azobenzene surfactant into potassium niobate.
AB  - The first successful synthesis of photoresponsive multilayer spiral nanotubes by
      the introduction of polyfluorinate cationic azobenzene derivative, trans-[2
      (2,2,3,3,4,4,4-heptafluorobutylamino)ethyl]-{2-[4-(4-hexyphenylazo)
      phenoxy]ethyl}dimethylammonium (abbreviated as C3F7-Azo+), into layered niobate
      interlayer I by a two-step guest-guest exchange method using the intercalation
      compound, methyl viologen (MV2+)-K4Nb6O17, as precursor is reported.

PMID- 16417335
TI  - Fractal-like self-assembly of oligo(p-phenylene vinylene) capped gold
      nanoparticles.
AB  - Reversible interparticle self-organization is reported for gold nanoparticles
      functionalized with an oligo(p-phenylene vinylene) moiety in butanol. The
      aggregates show a clear melting temperature at 80 degrees C, and atomic force
      microscopy and transmission electron microscopy indicate a fractal-like
      organization of the particles.

PMID- 16417336
TI  - Magnetic fluorescent delivery vehicle using uniform mesoporous silica spheres
      embedded with monodisperse magnetic and semiconductor nanocrystals.
AB  - We synthesized uniform pore-sized mesoporous silica spheres embedded with
      magnetite nanocrystal and quantum dots. The magnetic separation, luminescent
      detection, and controlled release of drugs were demonstrated using the uniform
      mesoporous silica spheres embedded with monodisperse nanocrystals.

PMID- 16417337
TI  - Intramolecular pi-dimerization in a 1,1'-bis(verdazyl)ferrocene diradical.
AB  - The solid state structure of 1,1'-bis(verdazyl)ferrocene reveals the two radical
      moieties associated intramolecularly to give the first example of a pi-dimer of a
      stable verdazyl radical. The pi-dimer structure is not maintained in solution.
      Magnetic characterization indicates that the radicals are sufficiently strongly
      antiferromagnetically coupled so as to render the molecule diamagnetic at room
      temperature.

PMID- 16417338
TI  - Electrochemical evaluation of alternating duplex-triplex conversion effect on the
      anthraquinone-photoinjected hole transport through DNA duplex immobilized on a
      gold electrode.
AB  - Amperometry was employed to characterize the anthraquinone (AQ)-photoinjected
      hole transport through a 20-mer oligodeoxynucleotide (ODN) duplex, as immobilized
      on the surface of a gold electrode, and its triplex forms converted by
      association with several third oligopyrimidine (OPD) short strands. While the
      cathodic photocurrent was observed upon irradiation at 365 nm of the AQ
      photosensitizer linked to the end of DNA duplex, a marked lowering of the current
      density was identified to occur by the triplex formation of a duplex with a given
      third OPD short strand. The photocurrent through the DNA duplex showed a
      reversible fall-rise response concomitant with alternating association
      dissociation cycle of the OPD short-strand, as regulated by temperature change
      around the corresponding melting temperature of the DNA triplex. Both the
      switched photoirradiation and the thermally alternating duplex-triplex conversion
      could provide tools of regulating the DNA hole transport.

PMID- 16417339
TI  - Intercepting palladacycles derived by C-H insertion. A mechanism-driven entry to
      heterocyclic tetraphenylenes.
AB  - Mechanistic support for the intermediacy of a palladacycle, which has been
      implicated in the crossover Heck reaction, has been obtained by intercepting this
      species using biphenylene. This leads to the formation of heterocyclic
      tetraphenylene derivatives. Three examples of this process are reported, and in
      two cases, the product structures have been confirmed by X-ray crystallographic
      analysis.

PMID- 16417341
TI  - Permeability of a seemingly nonporous crystal formed by a discrete metallocyclic
      complex.
AB  - We describe the structure and permeability of a crystalline material that appears
      to be nonporous in a conventional sense. The material is initially formed as a
      solvate, and removal of the solvent molecules under relatively mild conditions
      proceeds via a single-crystal to single-crystal transformation, leaving the host
      structure intact. Although discrete unoccupied voids of 108 A3 are present in the
      structure, it is not possible to map open channels that represent an intuitive
      pathway for guest diffusion. Despite the apparent absence of pores, the material
      is permeable to a variety of gases including H2, O2, N2, CO, CH4, CO2, and I2.
      These findings show that porosity in crystalline systems cannot always be
      rationalized by considering the static structures and that as-yet unknown dynamic
      and cooperative mechanisms prevail by which porosity can be induced.

PMID- 16417340
TI  - "Click peptide" based on the "o-acyl isopeptide method": control of A beta1-42
      production from a photo-triggered A beta1-42 analogue.
AB  - A clear understanding of the dynamic events of amyloid beta peptide (Abeta) 1-42,
      such as the folding, self-assembly, and aggregation processes, would be of great
      significance in Alzheimer's disease (AD) research. However, elucidation of these
      Abeta1-42 dynamic events is a difficult issue due to uncontrolled polymerization,
      which also poses a significant obstacle for establishing an experimental system
      that clarifies the pathological function of Abeta1-42. On the basis of the O-acyl
      isopeptide method, we herein developed a novel photo-triggered "click peptide" of
      Abeta1-42, for example, 26-N-Nvoc-26-AIAbeta42, in which the photocleavable 6
      nitroveratryloxycarbonyl (Nvoc) group was introduced at the alpha-amino group of
      Ser26 in 26-O-acyl isoAbeta1-42 (26-AIAbeta42). From the results, (1) the click
      peptide did not exhibit the self-assembling nature under physiological conditions
      due to one single modified ester; (2) photoirradiation of the click peptide and
      subsequent O-N intramolecular acyl migration afforded the intact Abeta1-42 with a
      quick and one-way conversion reaction (so-called "click"), while the click
      peptide was stable under nonphotolytic or storage conditions. In addition, it is
      advantageous that no additional fibril inhibitory auxiliaries were released
      during conversion to Abeta1-42. This method provides a novel system useful for
      investigating the dynamic biological functions of Abeta1-42 in AD by inducible
      activation of Abeta1-42 self-assembly.

PMID- 16417342
TI  - Direct formation of micro-/nanocrystalline 2,5-dimethyl-N,N'
      dicyanoquinonediimine complexes on SiO2/Si substrates and multiprobe measurement
      of conduction properties.
AB  - Multiprobe measurements were performed on tiny single crystals of DMe-DCNQI
      complexes prepared directly on SiO2/Si substrates. The differences in conduction
      properties between the micro- and nanocrystals and bulk crystals were observed.

PMID- 16417343
TI  - Twisted, Z-shaped perylene bisimide.
AB  - The first derivative of a new class of perylene bisimide chromophores, N,N'
      bis(octyl)-3,9-bis(phenyl)perylene-1,2,7,8-tetracarboxyl bisimide, 1, has been
      synthesized and its fundamental photophysical and electrochemical properties
      assessed. The extended, Z-shaped structure was achieved by use of the classic
      photoenolization of an o-methylbenzophenone analogue, 1,5-dibenzoyl-9,10
      dihydroanthracene, and in situ Diels-Alder trapping of the resulting o-xylylenol
      intermediates with N-octylmaleimide. Subsequent dehydration and aromatization of
      the resulting bisadduct afforded 1. In dichloromethane, bisimide 1 has an
      absorption lambdamax at 491 nm (epsilon = 29,600 M-1 cm-1), a fluorescence
      lambdamax at 517 nm with a high quantum yield (Phi = 0.70), and a single
      exponential fluorescence decay (tau = 5.01 ns). Pure crystals of 1 have red
      emission, suggesting exciplex formation in the solid state. X-ray
      crystallographic analysis of 1 revealed significant twisting of its perylene
      core.

PMID- 16417344
TI  - Crystal structures of the chiral lithiosilanes [(Lis)-PhMe2SiLi x THF x (-)
      sparteine] and [Ph2(NEt2)SiLi x (-)-sparteine].
AB  - The (-)-sparteine-coordinated lithiosilanes (Lis)-4 and 5 crystallize as monomers
      with coordination numbers of 4 and 3 on lithium and represent the first
      structurally characterized enantiopure lithiosilanes. Both systems are also
      monomeric in solution with Si-Li contacts detected by 29Si-7Li couplings in the
      29Si NMR spectrum (for 5 even at room temperature).

PMID- 16417345
TI  - BiScO3: centrosymmetric BiMnO3-type oxide.
AB  - With neutron powder diffraction, electron diffraction, and second-harmonic
      generation, we have shown that BiScO3 has a structure closely related to that of
      multiferroic BiMnO3, but BiScO3 crystallizes in the centrosymmetric space group
      of C2/c. These results bring up a question about the origin of ferroelectricity
      in BiMnO3. BiScO3 may serve as a model system to understand the role of Mn3+ ions
      in the ferroelectricity of BiMnO3.

PMID- 16417346
TI  - Helix-sense controlled polymerization of a single phenyl isocyanide enantiomer
      leading to diastereomeric helical polyisocyanides with opposite helix-sense and
      cholesteric liquid crystals with opposite twist-sense.
AB  - We report the unprecedented helix-sense controlled polymerization of
      enantiomerically pure phenyl isocyanides bearing an l- or d-alanine pendant with
      a long alkyl chain. The polymerization with an achiral nickel catalyst
      diastereoselectively proceeds, resulting in either a right- or left-handed
      helical polymer, whose helix-sense can be controlled by the polymerization
      solvent and temperature. Both the diastereomeric right- and left-handed helical
      polymers further self-assemble into lyotropic cholesteric liquid crystals with
      opposite twist-senses. Consequently, the macromolecular helicity and mesoscopic,
      supramolecular cholesteric twist can be controlled by the molecular chirality of
      the pendant of a single enantiomeric phenyl isocyanide through the polymerization
      under either kinetic or thermodynamic control assisted by hydrogen bonds. High
      resolution atomic force microscopy revealed their helical conformations and
      enabled the determination of the helical sense.

PMID- 16417347
TI  - The square-planar cytotoxic [Cu(II)(pyrimol)Cl] complex acts as an efficient DNA
      cleaver without reductant.
AB  - Chemical nucleases based on the transition-metal ions cleave DNA hydrolytically
      and/or oxidatively, with or without added reductant. We report here the novel DNA
      cleavage properties of the highly water-soluble, square-planar [Cu(Hpyrimol)Cl]
      complex, together with the results of cytotoxicities toward selected cancer cell
      lines. The copper complex cleaves PhiX174 supercoiled DNA efficiently without any
      reductant and shows high cytotoxicities toward L1210 murine leukemia and A2780
      human ovarian carcinoma cancer cell lines that are sensitive and resistant to
      cisplatin. The IC50 values obtained for the copper complex in the sensitive cell
      lines are in the range of cisplatin, and for the cisplatin-resistant leukemia
      cell line, this value is even better.

PMID- 16417348
TI  - Multi-electron transfer from heme-functionalized nanocrystalline TiO2 to
      organohalide pollutants.
AB  - Hemin (iron protoporphyrin IX) has been anchored to approximately 15 nm TiO2
      nanocrystallites (anatase) in approximately 8 mum thick mesoporous thin films.
      Band gap excitation of these materials in methanol or aqueous (pH 4 or 8)
      solutions leads to the reduction of hemin to heme (FeIII --> FeII) and the
      production of TiO2(e-), heme/TiO2(e-). The mechanisms and second-order rate
      constants for the reduction of bromobenzene, chlorobenzene, dichlorobenzene, and
      trichloroethylene were quantified. In all cases, the concentration of TiO2(e-)
      was found to decrease to near zero before the hemes were oxidized to hemin.
      Comparative studies with TiO2(e-) that were not functionalized with hemes
      indicate that organohalide reduction is mediated by the hemes. Reactions of 6
      bromo-1-hexene with heme/TiO2(e-) demonstrate multi-electron transfer reactivity
      and show that heme/TiO2(e-) nanocrystallites deliver two electrons to RX within
      4.5 mus.

PMID- 16417349
TI  - J-coupling nuclear magnetic resonance spectroscopy of liquids in nT fields.
AB  - In ultralow magnetic fields, liquid state nuclear magnetic resonance (NMR)
      spectra of homonuclear spin systems exhibit line widths dominated by their
      natural lifetime. Chemical shifts become negligible, and heteronuclear NMR
      spectra show predominantly the electron-mediated field-independent J-coupling.
      However, weak polarization and Larmor frequencies down to a few hertz require
      special detectors, such as Superconducting Quantum Interference Devices (SQUID),
      that also enable the simultaneous detection of broad band spectra of
      heteronuclear spin systems. We acquired spectra of 2,2,2-trifluoroethanol and
      trimethyl phosphate at detection fields varying from 444 nT to 3.34 muT after
      prepolarizing the sample in a field of 250 muT. Down to a 1H Larmor frequency of
      40 Hz, the spectra of trifluoroethanol exhibited four clearly resolvable peaks.
      The numerical simulation agreed well with the measured spectra. Trimethyl
      phosphate exhibited two major groups of nonresolved proton lines. At 1H Larmor
      frequencies below 150 Hz, the separation of the two groups decreased, reflecting
      the transition from weakly to strongly coupled spin systems. Direct determination
      of 3J(H,P) from the peak separation is possible only at Larmor frequencies above
      150 Hz. The experimental setup allowed an easy adjustment of the detection field
      over several octaves. This enabled us to adapt the detection field to the best
      suited measurement window providing the maximum spectral information. Low-field
      NMR may open new applications, such as monitoring heteronuclear reactions, low
      field imaging, simultaneous NMR/magnetoencephalography measurements, or quantum
      computing.

PMID- 16417350
TI  - Heterogeneous hydrogenation catalyses over recyclable Pd(0) nanoparticle
      catalysts stabilized by PAMAM-SBA-15 organic-inorganic hybrid composites.
AB  - Pd(0) nanoparticle catalysts stabilized by Gn-PAMAM-SBA-15 (n = 1-4) organic
      inorganic hybrid composites were successfully prepared. Heterogeneous
      hydrogenation reaction of allyl alcohol over the Pd(0)-Gn-PAMAM-SBA-15 catalysts
      showed their high activities with TOFs of 2185, 2266, 711, and 739 and
      selectivities of 79.0, 82.0, 93.4, and 91.4%, respectively. The activity over the
      Pd(0)-G4-PAMAM-SBA-15 catalyst was 1.5 times that over the fourth generation
      PAMAM encapsulated Pd(0) homogeneous catalyst. These catalysts can be easily
      recovered, reused multiple times, and preserved for one month in the air,
      maintaining high catalytic efficiencies.

PMID- 16417351
TI  - Highly enantioselective direct reductive coupling of conjugated alkynes and alpha
      ketoesters via rhodium-catalyzed asymmetric hydrogenation.
AB  - Catalytic hydrogenation of 1,3-enynes 1a-7a in the presence of ethyl pyruvate and
      related activated ketones using chirally modified cationic rhodium catalysts
      results in reductive coupling to afford dienylated alpha-hydroxy esters 1b-7b and
      3c-3f with exceptional levels of regio- and enantiocontrol. These studies
      represent the first highly enantioselective direct catalytic reductive couplings
      of alkynes to ketones. As illustrated by the conversion of 6b to 6c-6h, the diene
      containing the side chain of the coupling products is subject to diverse chemo-
      and regioselective manipulation. Reductive coupling of enyne 6a and ethyl
      pyruvate using elemental deuterium provides the monodeuterated product deuterio
      6b, consistent with a catalytic mechanism involving alkyne-carbonyl oxidative
      coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle, as
      corroborated by ESI-MS analysis.

PMID- 16417352
TI  - Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase
      2.
AB  - 5-Lipoxygenase and cyclooxygenase-2 (COX-2) initiate the biosynthesis of distinct
      families of mediators from arachidonic acid (leukotrienes and prostaglandins,
      respectively) and are each the target of anti-inflammatory medications. Here we
      show that the product of 5-lipoxygenase, 5S-hydroxyeicosatetraenoic acid, is
      selectively and efficiently triply oxygenated by COX-2, implicating a cross
      pathway interaction. The product is a unique diendoperoxide, potentially
      representing the parent compound of a novel group of lipid mediators.

PMID- 16417353
TI  - A simple catalytic synthesis of condensed pyridones from o-bromoarylcarboxamides
      involving ipso substitution via palladacycles.
AB  - A catalytic synthesis of condensed pyridones starting from o-bromoaromatic
      carboxamides is reported using Pd(OAc)2/TFP as catalyst, K2CO3 as a base in DMF
      at 105 degrees C. Under these conditions an unprecedented reaction sequence
      occurs leading to condensed pyridones in 23-86% yield. The proposed pathway
      proceeds through palladacycle-catalyzed homocoupling of the bromoamide, followed
      by intramolecular carbon-nitrogen bond-forming reaction with the carbon atom
      bearing the aminocarbonyl group, which is easily eliminated under palladium
      catalysis.

PMID- 16417354
TI  - Enzymatic assembly of the bis-indole core of rebeccamycin.
AB  - Rebeccamycin is a member of the family of indolocarbazole antibiotics with broad
      spectrum antitumor activity. The indolocarbazole framework is derived from two
      molecules of tryptophan, but very little is known about the enzymes involved in
      rebeccamycin biosynthesis. Here, we show that RebD is responsible for all
      catalytic steps forming the central pyrrole ring of chlorochromopyrrolic acid
      from two molecules of chloroindolepyruvic acid. This transformation does not
      require any additional cofactors and constitutes the first step of bis-indole
      formation in the biosynthesis of rebeccamycin.

PMID- 16417355
TI  - Significantly enhanced hydrogen storage in metal-organic frameworks via
      spillover.
AB  - The utilization of hydrogen in fuel-cell powered vehicles is limited by the lack
      of a safe and effective system for hydrogen storage. At the present time, there
      is no viable storage technology capable of meeting the DOE targets. Porous metal
      organic frameworks (MOFs) are novel and potential candidates for hydrogen
      storage. Until now it is still not possible to achieve any significant hydrogen
      storage capacity in MOFs at ambient temperature. Here, we report, for the first
      time, significant amounts of hydrogen storage in MOF-5 and IRMOF-8 at ambient
      temperature by using a very simple technique via hydrogen dissociation and
      spillover. Thus, hydrogen uptakes for MOF-5 and IRMOF-8 can be enhanced by a
      factor of 3.3 and 3.1, respectively (to nearly 2 wt % at 10 MPa and 298 K).
      Furthermore, the isotherms are totally reversible. These findings suggest that
      our technique is suitable for hydrogen storage in a variety of MOF materials
      because of their similar structures as MOF-5 and IRMOF-8.

PMID- 16417356
TI  - Thiocyanate hydrolase is a cobalt-containing metalloenzyme with a cysteine
      sulfinic acid ligand.
AB  - Thiocyanate hydrolase (SCNase) purified from Thiobacillus thioparus THI115
      hydrolyzes thiocyanate to carbonyl sulfide and ammonia. DNA sequences of the
      cloned genes revealed the close relation of SCNase to nitrile hydratase (NHase).
      The consensus sequences for coordination of the metal ion found in NHases were
      also conserved in the gamma subunit of SCNase. Here, we showed that the SCNase
      contained one cobalt atom per alphabetagamma heterotrimer. UV-vis absorption
      spectrum suggested that the cobalt exists as a non-corrin ion. Reduced SCNase
      showed an ESR signal characteristic of low-spin Co2+, which closely resembled
      that of the Co-type NHases. Mass spectrometry for the peptide fragment containing
      the metal-binding motif of the SCNase gamma subunit indicated that the cysteine
      residue at position 131 was post-translationally oxidized to a cysteine-sulfinic
      acid. From these results, we concluded that SCNases and NHases form a novel non
      corrin and/or non-heme protein family having post-translationally modified
      cysteine ligands.

PMID- 16417357
TI  - Real-time sizing of nanoparticles in microfluidic channels using confocal
      correlation spectroscopy.
AB  - This Communication reports real-time sizing of nanoparticles in microfluidic
      systems using confocal correlation spectroscopy (CCS). CCS can be used to measure
      the size of both fluorescent and nonfluorescent particles at low concentrations
      (<nanomolar) and in small volumes (<femtoliters). With advances in nonfluorescent
      modes of single-particle and single-molecule detection, we anticipate CCS will
      find broad use in the real-time measurements of nanoparticles and macromolecules.

PMID- 16417358
TI  - Enantioselective nitroaldol reaction of alpha-ketoesters catalyzed by cinchona
      alkaloids.
AB  - The development of highly enantioselective and general catalytic nitroaldol
      (Henry) reactions with ketones is a challenging yet desirable task in organic
      synthesis. In this communication, we report an asymmetric nitroaldol reaction
      with alpha-ketoesters catalyzed by a new C6'-OH cinchona alkaloid catalyst. This
      is the first highly efficient organocatalytic asymmetric Henry reaction with
      ketones. This reaction is operationally simple and affords high
      enantioselectivity as well as good to excellent yield for a broad range of alpha
      ketoesters.

PMID- 16417359
TI  - Organocatalytic direct asymmetric aldol reactions in water.
AB  - We have developed direct asymmetric cross-aldol reactions that can be performed
      in water without addition of organic solvents. A bifunctional catalyst with a
      long hydrophobic alkyl chain efficiently catalyzed the reactions and afforded the
      desired aldol products in excellent yield with high enantiomeric excess, even
      when only an equal molar ratio of the donor and acceptor was used. These results
      reveal an effective design strategy for the development of aqueous
      organocatalytic systems.

PMID- 16417360
TI  - Deuterium kinetic isotope effects in gas-phase S(N)2 and E2 reactions: comparison
      of experiment and theory.
AB  - The competition between bimolecular nucleophilc substitution and base-induced
      elimination is investigated through kinetic isotope effect measurements for gas
      phase reactions of RCl + ClO- (R = methyl, ethyl, isopropyl, and tert-butyl)
      utilizing a FA-SIFT instrument. The overall reaction rate constants and the
      kinetic isotope effect for the reaction of C2H5Cl + ClO- are compared to
      computational results. [Hu, W. P.; Truhlar, D. G. J. Am. Chem. Soc. 1996, 118,
      860.] Experimental results show that as the degree of substitution in the neutral
      reactant increases the E2 channel becomes dominant. The systematic change in the
      overall kinetic isotope effects indicates that, for the reaction of ClO- with
      C2H5Cl, both the SN2 and E2 pathways do occur, as predicted by computation;
      however the experimental reaction rate constants and KIE deviate strongly from
      the computational result.

PMID- 16417361
TI  - cis-[Rh2(mu-O2CCH3)2(CH3CN)6]2+ as a photoactivated cisplatin analog.
AB  - The complex cis-[Rh2(mu-O2CCH3)2(CH3CN)6]2+ (1) exchanges the two axial CH3CN
      ligands for solvent molecules in water to yield cis-[Rh2(mu
      O2CCH3)2(CH3CN)4(H2O)2]2+ (2). Photolysis of 2 in H2O results in the
      photoaquation of two equatorial acetonitrile ligands to yield [Rh2(mu
      O2CCH3)2(CH3CN)2(H2O)4]2+ (3), which is able to covalently bind to free 2,2'
      bipyridine (bpy) and 9-ethylguanine in solution, as well as double-stranded DNA
      (lambdairr >/= 455 nm). Complex 2 exhibits 20-fold lower cytotoxicity towards
      human skin cells than hematoporphyrin in the dark, and its toxicity increases by
      a factor of 34 when irradiated with visible light (400-700 nm, 30 min). This
      increase in cytotoxicity by 2 upon irradiation is approximately 7 times greater
      than that measured for hematoporphyrin. These properties make 2 a promising photo
      cisplatin analog and a potential agent for photodynamic therapy. To our
      knowledge, 2 is the first metal-metal bonded complex to bind to DNA upon
      irradiation with visible light.

PMID- 16417362
TI  - Concise total syntheses of palominol, dolabellatrienone, beta-araneosene, and
      isoedunol via an enantioselective Diels-Alder macrobicyclization.
AB  - Concise total syntheses of four members of the dolabellane family of diterpenoid
      natural products are reported. Key features of the developed route include the
      first demonstration of an enantioselective, intramolecular Type I Diels-Alder
      macrobicyclization, the first example of a stereoselective pi-allyl Stille
      coupling reaction involving a farnesyl-derived intermediate, a powerful new
      reagent for the formation of dithianes with acid-sensitive molecules, and a
      unique and highly efficient ring-contraction sequence based on a modified Wolff
      photochemical rearrangement.

PMID- 16417363
TI  - Sliding behavior of water droplets on flat polymer surface.
AB  - Flat films of methyl methacrylate-fluoroalkyl methacrylate copolymers were
      prepared, and their hydrophobicity was investigated. It was revealed that the F
      concentration directly affects the static hydrophobicity on the flat polymer
      surface in a systematic manner. Furthermore, the sliding behavior of a water
      droplet on these surfaces depends on the static hydrophobicity; the sliding
      motion changes from constant velocity to constant acceleration with an increase
      in the water contact angle.

PMID- 16417364
TI  - Multiple wurtzite twinning in CdTe nanocrystals induced by methylphosphonic acid.
AB  - Branching in semiconductor nanocrystals, which leads to tetrapods and to more
      complex architectures, is the subject of intensive investigation. Here we support
      the model according to which branching in CdTe nanocrystals is driven by the
      formation of multiple wurtzite twins. This is in contrast to previous models for
      this material. We found that twinning, as well as anisotropic growth, can be
      triggered by the presence of suitable molecules, such as for instance
      methylphosphonic acid. In the case of CdTe nanocrystals, we designed a robust
      growth scheme in which the variation of a single parameter (the concentration of
      methylphosphonic acid in solution) leads to the controlled formation of
      nanocrystals with shapes ranging from spheres to anisotropic structures with
      varying level of branching, as both twinning and anisotropic growth are
      progressively favored. We believe that these concepts can be extended to other
      nanocrystal systems.

PMID- 16417365
TI  - Studies of low-coordinate iron dinitrogen complexes.
AB  - Understanding the interaction of N2 with iron is relevant to the iron catalyst
      used in the Haber process and to possible roles of the FeMoco active site of
      nitrogenase. The work reported here uses synthetic compounds to evaluate the
      extent of NN weakening in low-coordinate iron complexes with an FeNNFe core. The
      steric effects, oxidation level, presence of alkali metals, and coordination
      number of the iron atoms are varied, to gain insight into the factors that weaken
      the NN bond. Diiron complexes with a bridging N2 ligand, L(R)FeNNFeL(R) (L(R) =
      beta-diketiminate; R = Me, tBu), result from reduction of [L(R)FeCl]n under a
      dinitrogen atmosphere, and an iron(I) precursor of an N2 complex can be observed.
      X-ray crystallographic and resonance Raman data for L(R)FeNNFeL(R) show a
      reduction in the N-N bond order, and calculations (density functional and
      multireference) indicate that the bond weakening arises from cooperative back
      bonding into the N2 pi orbitals. Increasing the coordination number of iron from
      three to four through binding of pyridines gives compounds with comparable N-N
      weakening, and both are substantially weakened relative to five-coordinate iron
      N2 complexes, even those with a lower oxidation state. Treatment of
      L(R)FeNNFeL(R) with KC8 gives K2L(R)FeNNFeL(R), and calculations indicate that
      reduction of the iron and alkali metal coordination cooperatively weaken the N-N
      bond. The complexes L(R)FeNNFeL(R) react as iron(I) fragments, losing N2 to yield
      iron(I) phosphine, CO, and benzene complexes. They also reduce ketones and
      aldehydes to give the products of pinacol coupling. The K2L(R)FeNNFeL(R)
      compounds can be alkylated at iron, with loss of N2.

PMID- 16417366
TI  - Carboxylic acid chemistry at the Ge(100)-2 x 1 interface: bidentate bridging
      structure formation on a semiconductor surface.
AB  - The reactions of acetic acid, acetic-d3 acid-d, and formic acid with the Ge(100)
      2 x 1 surface have been investigated using multiple internal reflection Fourier
      transform infrared (MIR-FTIR) spectroscopy, X-ray photoelectron spectroscopy
      (XPS), and density functional theory (DFT) calculations. The infrared and
      photoelectron data provide experimental evidence for an O-H dissociation product
      at 310 K. DFT calculations indicate that the O-H dissociation pathway is
      significantly favored, both kinetically and thermodynamically, over other
      potential reaction pathways. All of the carboxylic acids studied exhibit
      unexpected vibrational modes between 1400 and 1525 cm(-1), which are attributed
      to the presence of a bidentate bridging structure where both oxygen atoms
      interact directly with the surface.

PMID- 16417367
TI  - Quenching of fluorophore-labeled DNA oligonucleotides by divalent metal ions:
      implications for selection, design, and applications of signaling aptamers and
      signaling deoxyribozymes.
AB  - Recent years have seen a dramatic increase in the use of fluorescence-signaling
      DNA aptamers and deoxyribozymes as novel biosensing moieties. Many of these
      functional single-stranded DNA molecules are either engineered to function in the
      presence of divalent metal ion cofactors or designed as sensors for specific
      divalent metal ions. However, many divalent metal ions are potent fluorescence
      quenchers. In this study, we first set out to examine the factors that contribute
      to quenching of DNA-bound fluorophores by commonly used divalent metal ions, with
      the goal of establishing general principles that can guide future exploitation of
      fluorescence-signaling DNA aptamers and deoxyribozymes as biosensing probes. We
      then extended these studies to examine the effect of specific metals on the
      signaling performance of both a structure-switching signaling DNA aptamer and an
      RNA-cleaving and fluorescence-signaling deoxyribozyme. These studies showed
      extensive quenching was obtained when using divalent transition metal ions owing
      to direct DNA-metal ion interactions, leading to combined static and dynamic
      quenching. The extent of quenching was dependent on the type of metal ion and the
      concentration of supporting monovalent cations in the buffer, with quenching
      increasing with the number of unpaired electrons in the metal ion and decreasing
      with the concentration of monovalent ions. The extent of quenching was
      independent of the fluorophore, indicating that quenching cannot be alleviated
      simply by changing the nature of the fluorescent probe. Our results also show
      that the DNA sequence and the local secondary structure in the region of the
      fluorescent tag can dramatically influence the degree of quenching by divalent
      transition metal ions. In particular, the extent of quenching is predominantly
      determined by the fluorophore location with respect to guanine-rich and duplex
      regions within the strand sequence. Examination of the effect of both the type
      and concentration of metal ions on the performance of a fluorescence-signaling
      aptamer and a signaling deoxyribozyme confirms that judicious choice of divalent
      transition metal ions is important in maximizing signals obtained from such
      systems.

PMID- 16417368
TI  - Crossover from superexchange to hopping as the mechanism for photoinduced charge
      transfer in DNA hairpin conjugates.
AB  - The mechanism and dynamics of photoinduced charge separation and charge
      recombination have been investigated in synthetic DNA hairpins possessing donor
      and acceptor stilbenes separated by one to seven A:T base pairs. The application
      of femtosecond broadband pump-probe spectroscopy, nanosecond transient absorption
      spectroscopy, and picosecond fluorescence decay measurements permits detailed
      analysis of the formation and decay of the stilbene acceptor singlet state and of
      the charge-separated intermediates. When the donor and acceptor are separated by
      a single A:T base pair, charge separation occurs via a single-step superexchange
      mechanism. However, when the donor and acceptor are separated by two or more A:T
      base pairs, charge separation occurs via a multistep process consisting of hole
      injection, hole transport, and hole trapping. In such cases, hole arrival at the
      electron donor is slower than hole injection into the bridging A-tract. Rate
      constants for charge separation (hole arrival) and charge recombination are
      dependent upon the donor-acceptor distance; however, the rate constant for hole
      injection is independent of the donor-acceptor distance. The observation of
      crossover from a superexchange to a hopping mechanism provides a "missing link"
      in the analysis of DNA electron transfer and requires reevaluation of the
      existing literature for photoinduced electron transfer in DNA.

PMID- 16417370
TI  - Computational design of heterochiral peptides against a helical target.
AB  - Polypeptides incorporating D-amino acids occasionally occur in nature and are an
      important class of pharmaceutical molecules. With the use of heterochiral Monte
      Carlo (HCMC), a method inspired by the de novo design of proteins, we develop
      peptide scaffolds for interacting with a molecular target, a left-handed alpha
      helix. The HCMC approach concurrently seeks to optimize a peptide sequence, its
      internal conformation, and its docked conformation with a target surface. Several
      major classes of interactions are observed: (1) homochiral interactions between
      two alphaL helices, (2) heterochiral interactions between an alphaL and an alphaR
      helix, and (3) heterochiral interactions between the alphaL target and novel
      nonhelical structures. We explore the application of HCMC to simulating the
      preferential enantioselectivity of heterochiral complexes. Implications for
      biomimetic design in molecular recognition are discussed.

PMID- 16417369
TI  - Ultrafast excited-state dynamics in vitamin B12 and related cob(III)alamins.
AB  - Femtosecond transient IR and visible absorption spectroscopies have been employed
      to investigate the excited-state photophysics of vitamin B12 (cyanocobalamin,
      CNCbl) and the related cob(III)alamins, azidocobalamin (N3Cbl), and aquocobalamin
      (H2OCbl). Excitation of CNCbl, H2OCbl, or N3Cbl results in rapid formation of a
      short-lived excited state followed by ground-state recovery on time scales
      ranging from a few picoseconds to a few tens of picoseconds. The lifetime of the
      intermediate state is influenced by the sigma-donating ability of the axial
      ligand, decreasing in the order CNCbl > N3Cbl > H2OCbl, and by the polarity of
      the solvent, decreasing with increasing solvent polarity. The peak of the excited
      state visible absorption spectrum is shifted to ca. 490 nm, and the shape of the
      spectrum is characteristic of weak axial ligands, similar to those observed for
      cob(II)alamin, base-off cobalamins, or cobinamides. Transient IR spectra of the
      upper CN and N3 ligands are red-shifted 20-30 cm(-1) from the ground-state
      frequencies, consistent with a weakened Co-upper ligand bond. These results
      suggest that the transient intermediate state can be attributed to a corrin ring
      pi to Co 3d(z2) ligand to metal charge transfer (LMCT) state. In this state bonds
      between the cobalt and the axial ligands are weakened and lengthened with respect
      to the corresponding ground states.

PMID- 16417371
TI  - Polyanionic hydrides from polar intermetallics AeE2 (Ae = Ca, Sr, Ba; E = Al, Ga,
      In).
AB  - The hydrogenation behavior of the polar intermetallic systems AeE2 (Ae = Ca, Sr,
      Ba; E = Al, Ga, In) has been investigated systematically and afforded the new
      hydrides SrGa2H2 and BaGa2H2. The structure of these hydrides was characterized
      by X-ray powder diffraction and neutron diffraction of the corresponding
      deuterides. Both compounds are isostructural to previously discovered SrAl2H2
      (space group P3m1, Z = 1, SrGa2H2/D2: a = 4.4010(4)/4.3932(8) A, c =
      4.7109(4)/4.699(1) A; BaGa2H2/D2: a = 4.5334(6)/4.5286(5) A, c =
      4.9069(9)/4.8991(9) A). The three hydrides SrAl2H2, SrGa2H2, and BaGa2H2
      decompose at around 300 degrees C at atmospheric pressure. First-principles
      electronic structure calculations reveal that H is unambiguously part of a two
      dimensional polyanion [E2H2]2- in which each E atom is tetrahedrally coordinated
      by three additional E atoms and H. The compounds AeE2H2 are classified as
      polyanionic hydrides. The peculiar feature of polyanionic hydrides is the
      incorporation of H in a polymeric anion where it acts as a terminating ligand.
      Polyanionic hydrides provide unprecedented arrangements with both E-E and E-H
      bonds. The hydrogenation of AeE2 to AeE2H2 takes place at low reaction
      temperatures (around 200 degrees C), which suggests that the polyanion of the
      polar intermetallics ([E2]2-) is employed as precursor.

PMID- 16417373
TI  - Ab initio calculations of the reaction mechanisms for metal-nitride deposition
      from organo-metallic precursors onto functionalized self-assembled monolayers.
AB  - An atomistic mechanism has been derived for the initial stages of the adsorption
      reaction for metal-nitride atomic layer deposition (ALD) from alkylamido
      organometallic precursors of Ti and Zr on alkyltrichorosilane-based self
      assembled monolayers (SAMs). The effect of altering the terminal functional group
      on the SAM (including -OH, -NH2, -SH, and -NH(CH3)) has been investigated using
      the density functional theory and the MP2 perturbation theory. Reactions on amine
      terminated SAMs proceed through the formation of a dative-bond complex with an
      activation barrier of 16-20 kcal/mol. In contrast, thiol-terminated SAMs form
      weak hydrogen-bonded intermediates with activation barriers between 7 and 10
      kcal/mol. The deposition of Ti organometallic precursors on hydroxyl-terminated
      SAMs proceeds through the formation of stronger hydrogen-bonded complexes with
      barriers of 7 kcal/mol. Zr-based precursors form dative-bonded adducts with near
      barrierless transitions. This variety allows us to select a kinetically favorable
      substrate for a chosen precursor. The predicted order of reactivity of
      differently terminated SAMs and the temperature dependence of the initial
      reaction probability have been confirmed for Ti-based precursors by recent
      experimental results. We predict that the replacement of methyl groups by
      trifluoromethyl groups on the SAM backbone decreases the activation barrier for
      amine-terminated SAMs by 5 kcal/mol. This opens a route to alter the native
      reactivities of a given SAM termination, in this case making amine termination
      energetically viable. The surface distribution of SAM molecules has a strong
      effect on the adsorption kinetics of Ti-based precursors. Unimolecular side
      decomposition reactions were found to be kinetically competitive with adsorption
      at 400 K.

PMID- 16417372
TI  - Photoregulated transmembrane charge separation by linked spiropyran-anthraquinone
      molecules.
AB  - Amide-linked spiropyran-anthraquinone (SP-AQ) conjugates were shown to mediate
      ZnTPPS(4-)-photosensitized transmembrane reduction of occluded Co(bpy)3(3+)
      within unilamellar phosphatidylcholine vesicles by external EDTA. Overall quantum
      yields for these reactions were dependent upon the isomeric state of the dye;
      specifically, 30-35% photoconversion of the closed-ring spiropyran (SP) moiety to
      the open-ring merocyanine (MC) form caused the quantum yield to decrease by 6
      fold in the simple conjugate and 3-fold for an analogue containing a lipophilic 4
      dodecylphenoxy substituent on the anthraquinone moiety. Transient spectroscopic
      and fluorescence quenching measurements revealed that two factors contributed to
      these photoisomerization-induced changes in quantum yields: increased
      efficiencies of fluorescence quenching of 1ZnTPPS4- by the merocyanine group and
      lowered transmembrane diffusion rates of the merocyanine-containing redox
      carriers. Transient spectrophotometry also revealed the sequential formation and
      decay of two reaction intermediates, identified as 3ZnTPPS4- and a species with
      the optical properties of a semiquinone radical. Kinetic profiles for
      Co(bpy)3(3+) reduction under continuous photolysis in the presence and absence of
      added ionophores indicated that transmembrane redox mediated by SP-AQ was
      electroneutral, but reaction by the other quinone-containing mediators was
      electrogenic. The minimal reaction mechanism suggested from the combined studies
      is oxidative quenching of vesicle-bound 3ZnTPPS4- by the anthraquinone unit,
      followed by either H+/e- cotransport by transmembrane diffusion of SP-AQH* or,
      for the other redox mediators, semiquinone anion-quinone electron exchange
      leading to net transmembrane electron transfer, with subsequent one-electron
      reduction of the internal Co(bpy)3(3+). Thermal one-electron reduction of
      Co(bpy)3(3+) by EDTA is energetically unfavorable; the photosensitized reaction
      therefore occurs with partial conversion of photonic energy to chemical and
      transmembrane electrochemical potentials.

PMID- 16417374
TI  - Molecular dynamics simulations of surfactant self-organization at a solid-liquid
      interface.
AB  - Self-organization of aqueous surfactants at a planar graphite-like surface is
      studied by means of coarse-grain molecular dynamics simulations. The nonionic
      surfactant, n-alkyl poly(ethylene oxide), and water are both represented by
      coarse-grain models while an implicit representation is used for the graphite
      surface. The observed morphology of the aggregated surfactants depends on the
      alkyl chain length. Surfactants with a short chain form a monolayer on the
      graphite surface with a thickness roughly equal to that of the alkane tail. On
      the other hand, longer-tail surfactants form continuous hemicylinders on the
      surface with diameter approximately 5.0 +/- 0.5 nm, in good agreement with
      experimental AFM data.

PMID- 16417375
TI  - The C(2v) structure of enolic acetylacetone.
AB  - It has often been postulated that the lowest energy enolic form of Acetylacetone
      (AcAc) assumes C(s) symmetry, i.e., has a double-minimum potential possibly
      exhibiting a low barrier to internal proton transfer and not a single minimum,
      C(2v). Recent theoretical calculations and experimental work support the C(s)
      hypothesis but the literature on this fascinating molecule is divided. Toward
      this objective, the high-resolution rotational spectra of enolic acetylacetone
      and 3 isotopologues have been obtained, revealing C(2v) symmetry. The two methyl
      groups exhibit a very low barrier to internal rotation, thus making AcAc
      internally highly dynamic.

PMID- 16417376
TI  - Light stamping lithography: microcontact printing without inks.
AB  - We report a new patterning method, called light-stamping lithography (LSL), that
      uses UV-induced adhesion of poly(dimethylsiloxane) (PDMS). LSL is based on the
      direct transfer of the contact surface of the PDMS stamp to a substrate via a UV
      (254 nm)-induced surface bonding between the stamp and the substrate. This
      procedure can be adopted in automated printing machines that generate patterns
      with a wide range of feature sizes on diverse substrates. To demonstrate its
      usefulness, the LSL method was applied to prepare several PDMS patterns on a
      variety of substrates. The PDMS patterns were then used as templates for
      selective deposition of TiO2 thin film using atomic layer deposition as well as
      resists for selective wet etching.

PMID- 16417377
TI  - Zwitterionic metalates of group 11 elements and their use as metalloligands for
      the assembly of multizwitterionic clusters.
AB  - Reaction of RNHC(S)PPh2NPPh2C(S)NR (HRSNS; R = Me, Et) with M(I) (M = Cu, Ag, Au)
      salts afforded zwitterionic complexes of the general formula [M(RSNS)] (M = Cu,
      Ag, Au). The ligand was found in the solid state in S,S-kappa2 and S,N,S-kappa3
      coordination fashions. [Cu(RSNS)] and [Ag(RSNS)] can be used as metalloligand
      building blocks for the assembly of pentanuclear multizwitterionic Cu5, Cu3Ag2
      and Ag5 core clusters of the general formula [M'2{M(RSNS)}3]2+ (M = Cu, M' = Cu,
      Ag; M = M' = Ag) upon reaction with suitable M' salts. The crystal structures of
      the most significant compounds are reported herein. Compound
      [Ag2{Ag(RSNS)}2(OTf)2] was also isolated and structurally characterized,
      representing a model for the intermediate species of the aforementioned assembly.

PMID- 16417378
TI  - Rapid access to unexplored chemical space by ligand scanning around a ruthenium
      center: discovery of potent and selective protein kinase inhibitors.
AB  - An important objective for the discovery of compounds with unique biological
      activities is the development of methods for the synthesis of molecular scaffolds
      with defined three-dimensional shapes. We are currently investigating the scope
      of using metal complexes to accomplish this goal. In these compounds, the metal
      center has the role of organizing the orientation of the organic ligands, thus
      defining the overall shape of the molecule. A strategy is presented that allows a
      rapid scanning of ligands around a ruthenium center in the search for ligand
      spheres that are complementary in shape and functional group presentation to ATP
      binding sites of protein kinases. Following this approach, we have identified
      octahedral ruthenium complexes as potent inhibitors for the protein kinases Pim1,
      MSK1, and GSK3alpha.

PMID- 16417380
TI  - Synthesis, structural, and electron topographical analyses of a dialkylbiaryl
      phosphine/arene-ligated palladium(I) dimer: enhanced reactivity in Suzuki-Miyaura
      coupling reactions.
AB  - The treatment of bis(2-(dicyclohexylphosphino)-2',6'-dimethoxybiphenyl)PdCl2 with
      AgBF4 produces an air-stable phosphine/arene-ligated Pd(I) dimer with two
      seemingly identical Pd-arene interactions by X-ray crystallography. However, NMR
      and theoretical electron topographical analyses of this complex distinguish
      between these two interactions. One interaction is classified as an arenium-like
      complex, while the other is classified as a pi-interaction. Additionally, this
      complex is a suitable precatalyst for high yielding Suzuki-Miyaura coupling
      reactions in short reaction times.

PMID- 16417381
TI  - Infrared spectroscopy of hydrated amino acids in the gas phase: protonated and
      lithiated valine.
AB  - We report here infrared spectra of protonated and lithiated valine with varying
      degrees of hydration in the gas phase and interpret them with the help of DFT
      calculations at the B3LYP/6-31++G** level. In both the protonated and lithiated
      species our results clearly indicate that the solvation process is driven first
      by solvation of the charge site and subsequently by formation of a second
      solvation shell. The infrared spectra of Val x Li+ (H2O)4 and Val x H+ (H2O)4 are
      strikingly similar in the region of the spectrum corresponding to hydrogen-bonded
      stretches of donor water molecules, suggesting that in both cases similar
      extended water structures are formed once the charge site is solvated. In the
      case of the lithiated species, our spectra are consistent with a conformation
      change of the amino acid backbone from syn to anti accompanied by a change in the
      lithium binding from a NO coordination to OO coordination configuration upon
      addition of the third water molecule. This change in the mode of metal ion
      binding was also observed previously by Williams and Lemoff [J. Am. Soc. Mass
      Spectrom. 2004, 15, 1014-1024] using blackbody infrared radiative dissociation
      (BIRD). In contrast to the zwitterion formation inferred from results of the BIRD
      experiments upon addition of a third water molecule, our spectra, which are a
      more direct probe of structure, show no evidence for zwitterion formation with
      the addition of up to four water molecules.

PMID- 16417379
TI  - Chemical synthesis and molecular recognition of phosphatase-resistant analogues
      of phosphatidylinositol-3-phosphate.
AB  - The remodeling of phosphatidylinositol polyphosphates in cellular membranes by
      phosphatases and kinases orchestrates the signaling by these lipids in space and
      time. To provide chemical tools to study the changes in cell physiology mediated
      by these lipids, three new metabolically stabilized (ms) analogues of
      phosphatidylinositol-3-phosphate (PtdIns(3)P) were synthesized. We describe
      herein the total asymmetric synthesis of 3-methylphosphonate, 3
      (monofluoromethyl)phosphonate and 3-phosphorothioate analogues of PtdIns(3)P.
      From differentially protected D-myo-inositol key intermediates, a versatile
      phosphoramidite reagent was employed in the synthesis of PtdIns(3)P analogues
      with diacylglyceryl moieties containing dioleoyl, dipalmitoyl, and dibutyryl
      chains. In addition, we introduce a new phosphorylation reagent,
      (monofluoromethyl)phosphonyl chloride, which has general applications for the
      preparation of "pKa-matched" monofluorophosphonates. These ms-PtdIns(3)P
      analogues exhibited reduced binding activities with 15N-labeled FYVE and PX
      domains, as significant 1H and 15N chemical shift changes in the FYVE domain were
      induced by titrating ms-PtdIns(3)P analogues into membrane-mimetic
      dodecylphosphocholine micelles. In addition, the PtdIns(3)P analogues with
      dioleoyl and dipalmitoyl chains were substrates for the 5-kinase enzyme PIKfyve;
      the corresponding phosphorylated ms-PI(3,5)P2 products were detected by radio-TLC
      analysis.

PMID- 16417382
TI  - Support effect in high activity gold catalysts for CO oxidation.
AB  - In this work, we present a detailed study concerning the evaluation of the metal
      support interaction in high activity gold catalysts for CO oxidation. Using the
      colloidal deposition method, model catalysts were prepared, which allow the
      isolation of the effect of the support on the catalytic activity. Prefabricated
      gold particles were thus deposited on different support materials. Since the
      deposition process did not change the particle sizes of the gold particles, only
      the influence of the support could be studied. TiO2, Al2O3, ZrO2, and ZnO were
      used as support materials. Catalytic tests and high resolution transmission
      electron microscopy clearly show that the support contributes to the activity.
      However, our results are not in line with the distinction between active and
      passive supports based on the semiconducting properties of the oxidic material.
      The most active catalysts were obtained with TiO2 and Al2O3, while ZnO and ZrO2
      gave substantially less active catalysts. Furthermore, the effect of other
      important parameters on the catalytic activity (i.e., particles size
      distribution, calcination temperature, and aging time for a Au/TiO2 catalyst) has
      also been studied. Using this preparation route, the catalysts show high
      temperature stability, size dependent activity, and a very good long-term
      stability.

PMID- 16417384
TI  - Effect of functional group (fluorine) of aromatic thiols on electron transfer at
      the molecule-metal interface.
AB  - Electron transfer at the molecule-metal interface of self-assembled monolayers of
      1,1';4',1''-terphenyl-4''-thiol (BBB) and its partially fluorinated counterpart
      (BFF: p-thiophenyl-nonafluorobiphenyl) on Au(111) is investigated by core-hole
      clock spectroscopy. Ultrafast electron transfer at the BBB/Au(111) interface in
      the low-femtosecond regime (on the same time scale as the C 1s core-hole
      lifetime, approximately 6 fs) was observed. In contrast, for BFF/Au(111), the
      interface electron transfer was forbidden during the core-hole decay. This
      strongly suggests that fluorination of phenyl rings significantly enhances the
      localization of the excited electrons in the LUMO.

PMID- 16417385
TI  - A nitridoniobium(V) reagent that effects acid chloride to organic nitrile
      conversion: synthesis via heterodinuclear (Nb/Mo) dinitrogen cleavage,
      mechanistic insights, and recycling.
AB  - The transformation of acid chlorides (RC(O)Cl) to organic nitriles (RC[triple
      bond]N) by the terminal niobium nitride anion [N[triple bond]Nb(N[Np]Ar)3]- ([1a
      N]-, where Np = neopentyl and Ar = 3,5-Me2C6H3) via isovalent N for O(Cl)
      metathetical exchange is presented. Nitrido anion [1a-N]- is obtained in a
      heterodinuclear N2 scission reaction employing the molybdenum trisamide system,
      Mo(N[R]Ar)3 (R = t-Bu, 2a; R = Np, 2b), as a reaction partner. Reductive scission
      of the heterodinuclear bridging N2 complexes, (Ar[R]N)3Mo-(mu-N2)Nb(N[Np]Ar)3 (R
      = t-Bu, 3b; R = Np, 3c) with sodium amalgam provides 1 equiv each of the salt
      Na[1a-N] and neutral N[triple bond]Mo(N[R]Ar)3 (R = t-Bu, 2a-N; R = Np, 2b-N).
      Separation of 2-N from Na[1a-N] is readily achieved. Treatment of salt Na[1a-N]
      with acid chloride substrates in tetrahydrofuran (THF) furnishes the
      corresponding organic nitriles concomitant with the formation of NaCl and the oxo
      niobium complex O[triple bond]Nb(N[Np]Ar)3 (1a-O). Utilization of 15N-labeled
      15N2 gas in this chemistry affords a series of 15N-labeled organic nitriles
      establishing the utility of anion [1a-N]- as a reagent for the 15N-labeling of
      organic molecules. Synthetic and computational studies on model niobium systems
      provide evidence for the intermediacy of both a linear acylimido and
      niobacyclobutene species along the pathway to organic nitrile formation. High
      yield recycling of oxo 1a-O to a niobium triflate complex appropriate for
      heterodinuclear N2 scission has been developed. Specifically, addition of triflic
      anhydride (Tf2O, where Tf = SO2CF3) to an Et2O solution of 1a-O provides the
      bistriflate complex, Nb(OTf)2(N[Np]Ar)3 (1a-(OTf)2), in near quantitative yield.
      One-electron reduction of 1a-(OTf)2 with either cobaltocene (Cp2Co) or
      Mg(THF)3(anthracene) provided the monotriflato complex, Nb(OTf)(N[Np]Ar)3 (1a
      (OTf)), which efficiently regenerates complexes 3b and 3c when treated with the
      molybdenum dinitrogen anions [N2Mo(N[t-Bu]Ar)3]- ([2a-N2]-) or [N2Mo(N[Np]Ar)3]-
      ([2b-N2]-), respectively.

PMID- 16417383
TI  - Enantioselective TADMAP-catalyzed carboxyl migration reactions for the synthesis
      of stereogenic quaternary carbon.
AB  - The chiral, nucleophilic catalyst TADMAP [1, 3-(2,2,2-triphenyl-1-acetoxyethyl)-4
      (dimethylamino)pyridine] has been prepared from 3-lithio-4
      (dimethylamino)pyridine (5) and triphenylacetaldehyde (3), followed by acylation
      and resolution. TADMAP catalyzes the carboxyl migration of oxazolyl, furanyl, and
      benzofuranyl enol carbonates with good to excellent levels of enantioselection.
      The oxazole reactions are especially efficient and are used to prepare chiral
      lactams (23) and lactones (30) containing a quaternary asymmetric carbon. TADMAP
      catalyzed carboxyl migrations in the indole series are relatively slow and
      proceed with inconsistent enantioselectivity. Modeling studies (B3LYP/6-31G*)
      have been used in qualitative correlations of catalyst conformation, reactivity,
      and enantioselectivity.

PMID- 16417386
TI  - Real-time monitoring of chemical transformations by ultrafast 2D NMR
      spectroscopy.
AB  - An approach enabling the acquisition of 2D nuclear magnetic resonance (NMR)
      spectra within a single scan has been recently proposed. A promising application
      opened up by this "ultrafast" data acquisition format concerns the monitoring of
      chemical transformations as they happen, in real time. The present paper
      illustrates some of this potential with two examples: (i) following an H/D
      exchange process that occurs upon dissolving a protonated protein in D2O, and
      (ii) real-time in situ tracking of a transient Meisenheimer complex that forms
      upon rapidly mixing two organic reactants inside the NMR observation tube. The
      first of these measurements involved acquiring a train of 2D 1H-15N HSQC NMR
      spectra separated by ca. 4 s; following an initial dead time, this allowed us to
      monitor the kinetics of hydrogen exchange in ubiquitin at a site-resolved level.
      The second approach enabled us to observe, within ca. 2 s after the triggering of
      the reaction, a competition between thermodynamic and kinetic controls via
      changes in a series of 2D TOCSY patterns. The real-time dynamic experiments
      hereby introduced thus add to an increasing family of fast characterization
      techniques based on 2D NMR; their potential and limitations are briefly
      discussed.

PMID- 16417387
TI  - Triplet diphenylcarbenes protected by trifluoromethyl and bromine groups. A
      triplet carbene surviving a day in solution at room temperature.
AB  - Two types of diphenyldiazomethanes having two trifluoromethyl and two bromine
      groups at the ortho positions, either in unsymmetrical or in symmetrical fashion,
      that is, (2,6-dibromo-4-phenylphenyl)[4-phenyl-2,6
      bis(trifluoromethyl)phenyl]diazomethane (U-1-N2) and bis(2-bromo-4-phenyl-6
      trifluoromethylphenyl)diazomethane (S-1-N2), are prepared. Triplet
      diphenylcarbenes (U-(3)1 or S-(3)1) are generated from those precursors and are
      characterized by ESR, UV/vis spectroscopy at low temperature, as well as time
      resolved UV/vis spectroscopy at room temperature. Those carbenes are shown to be
      at least 2 orders of magnitude less reactive than the most stable triplet
      diphenylcarbene thus far known, that is, bis(2,6-dibromo-4-phenylphenyl)carbene.
      It has been also shown that S-(3)1 is significantly more stable than U-(3)1 even
      though both have the same two kinds of substituents. It is suspected that the
      perpendicular alignment of the two most bulky groups is a more effective way to
      shield the carbenic center than the planar one. By this way, triplet substituted
      diphenylcarbene surviving nearly a day in solution at room temperature is
      realized for the first time.

PMID- 16417388
TI  - Shape and aggregation control of nanoparticles: not shaken, not stirred.
AB  - The aggregation of nanoparticles during synthesis, particularly the effect of
      mechanical agitation, is investigated from a viewpoint of nucleation using a
      conjugated polymer, polyaniline, as an example. Homogeneous nucleation of
      polyaniline results in nanofibers, while heterogeneous nucleation leads to
      granular particulates. Mechanical agitation, which is a common method for
      disrupting aggregates, instead dramatically triggers aggregation during the
      synthetic process and favors the formation of granular particulates. Correlating
      the shape and aggregation of polyaniline nanoparticles with the mode of
      nucleation, a new aggregation mechanism is proposed in which aggregation is
      triggered by heterogeneous nucleation. The mechanism may be quite general as
      indicated by experiments with other materials such as silica nanoparticles.
      Highly dispersible polyaniline nanofibers can now be reproducibly prepared from a
      conventional reaction simply by not mechanically agitating the reaction and
      carrying it out at an elevated temperature. This work may prove to be of great
      value in reproducibly synthesizing nanoparticles with well-controlled sizes and
      shapes and in effectively preventing aggregation in chemical, pharmaceutical, and
      materials production processes.

PMID- 16417389
TI  - Coupled cluster and density functional theory studies of the vibrational
      contribution to the optical rotation of (S)-propylene oxide.
AB  - In a previous study (Chemical Physics Letters 2005, 401 , 385) we computed the
      optical rotatory dispersion of (S)-propylene oxide in gas phase and solution
      using the hierarchy of coupled cluster models CCS, CC2, CCSD, and CC3. Even for
      the highly correlated CC3 model combined with a flexible basis set, the
      theoretical gas-phase specific rotation at 355 nm was found to be negative in
      contrast to the experimental result. We argued that vibrational contributions
      could be crucial for obtaining a complete understanding of the experimental
      result. Here, we show that this indeed is the case by using coupled cluster
      models and density functional theory methods to calculate the vibrational
      contributions to the gas-phase specific rotation at 355, 589.3, and 633 nm. While
      density functional theory (B3LYP and SAOP functionals) overestimates the specific
      rotation at 355 nm by approximately 1 order of magnitude and yields an incorrect
      sign at 589.3 and 633 nm, the coupled cluster results are in excellent agreement
      with the experimentally measured optical rotations. We find that all vibrational
      modes contribute significantly to the optical rotation and that temperature
      effects must be taken into account.

PMID- 16417390
TI  - Toward functional pi-conjugated organophosphorus materials: design of phosphole
      based oligomers for electroluminescent devices.
AB  - The photophysical, electrochemical, and optoelectronic properties of conjugated
      systems incorporating dibenzophosphole or phosphole moieties are described.
      Dibenzophosphole derivatives are not suitable materials for OLEDs due to their
      weak photoluminescence (PL) in the solid state and the instability of the
      devices. Variation of the substitution pattern of phospholes and chemical
      modification of their P atoms afford thermally stable derivatives, which are
      photo- and electroluminescent. Comparison of the optical properties of solution
      and thin film of thioxophospholes shows that these compounds do not form
      aggregates in the solid state. This property, which is also supported by an X-ray
      diffraction study of three novel derivatives, results in an enhancement of the
      fluorescence quantum yields in the solid state. In contrast, (phosphole)gold(I)
      complexes exhibit a broad emission in thin film, which is due to the formation of
      aggregates. Single- and multilayer OLEDs using these P derivatives as the
      emissive layer have been fabricated. The emission color of these devices and
      their performances vary with the nature of the P material. Interestingly, di(2
      thienyl)thiooxophosphole is an efficient host for the red dopant DCJTB, and
      devices using the gold complexes have broad emission spectra.

PMID- 16417391
TI  - Room-temperature high-spin organic single molecule: nanometer-sized and
      hyperbranched poly[1,2,(4)-phenylenevinyleneanisylaminium].
AB  - Poly[1,2,(4)-phenylenevinyleneanisylaminium] 1 was synthesized by one-pot
      palladium-catalyzed polycondensation of N-(3-bromo-4-vinylphenyl)-N-(4
      methoxyphenyl)-N-(4-vinylphenyl)amine 3 and subsequent oxidation with the
      thianthrene cation radical tetrafluoroborate: compound 1 three-directionally
      satisfies a non-Kekule-type pi-conjugation and the ferromagnetic connectivity of
      the unpaired electrons of the triarylaminium cationic radical. The average
      molecular weight of the polymer was 4700-5900 (degree of polymerization = 11-14),
      which gave a single molecular-based and globular-shaped image of ca. 15 nm
      diameter by atomic and magnetic force microscopies under ambient conditions. The
      aminium polyradical 1 with a spin concentration (determined by iodometry) of 0.65
      spin/unit displayed an average S (spin quantum number) value of 7/2 even at 70
      degrees C according to NMR and magnetization measurements.

PMID- 16417392
TI  - Time-resolved thermodynamics: heat capacity change of transient species during
      photoreaction of PYP.
AB  - Heat capacity changes of short-lived transient species in different time ranges
      were measured for the first time by using the thermal component of the transient
      grating and transient lens signals at various temperatures. This method was
      applied to the transient intermediates of Photoactive Yellow Protein (PYP). The
      temperature dependence of the enthalpy change shows that the heat capacity of the
      short-lived intermediate pR2 (also called I1 or PYP(L)) species is the same as
      that of the ground state (pG) species within our experimental accuracy, whereas
      that of the long-lived intermediate pB (I2 or PYP(M)) is much larger (2.7 +/- 0.4
      kJ/mol K) than that of pG. The larger heat capacity is interpreted in terms of
      the conformational change of the pB species such as melted conformation and/or
      exposure of the nonpolar residues to the aqueous phase. This technique can be
      used for photochemical reactions in general to investigate the conformational
      change and the hydrophobic interaction in a time domain.

PMID- 16417393
TI  - Azobenzene-tethered T7 promoter for efficient photoregulation of transcription.
AB  - Azobenzene was additionally introduced into side chain of T7 promoter for the
      photocontrol of transcription reaction by T7 RNA polymerase (T7 RNAP). When a
      single azobenzene molecule was introduced into the T7 promoter either at the loop
      binding region of the RNAP (-7 to -11 position) or at the unwinding region (-1 to
      -4 position), transcription was suppressed in the trans-form but proceeded faster
      in the cis-form. The amount of transcripts after UV irradiation with respect to
      that in the dark was 1.5-2.0-fold. Kinetic analysis of the transcription reaction
      revealed that the photoregulatory mechanism was different in these positions. The
      photoisomerization of an azobenzene at the loop-binding region primarily affected
      Km. On the other hand, the isomerization of an azobenzene at the unwinding region
      mainly affected kcat. Still more clear-cut photoregulation was achieved when two
      azobenzenes were introduced into both loop-binding and unwinding regions,
      respectively: transcription proceeded 7.6-fold faster after UV irradiation than
      that in the dark. This synergistic effect was observed only when two azobenzenes
      were introduced into these two different regions, respectively, and introduction
      of them into the same loop-binding region drastically lowered the transcription
      activity. The cooperation of two azobenzenes at loop-binding and unwinding
      regions would contribute to the clear-cut photoregulation of transcription.

PMID- 16417394
TI  - Total synthesis of (+/-)-jiadifenin and studies directed to understanding its
      SAR: probing mechanistic and stereochemical issues in palladium-mediated
      allylation of enolate-like structures.
AB  - The total synthesis of jiadifenin has been accomplished. The synthesis allows us
      to build an SAR profile which suggests that the jiadifenin skeleton may be less
      desirable from the standpoint of nominating a potential drug than that of its
      prerearrangement precursor. The key steps of the jiadifenin problem involve the
      construction of two 1,3-related quaternary carbons. The paper describes how the
      stereochemistry was managed in this context. The issue was studied in
      considerable detail at the level of a then new allyl transfer reaction arising
      from a palladium-mediated transfer process of an allyl carbonate. By use of
      externally deuterated diallyl carbonate, we could probe, for the first time, the
      stereochemical relationship between the inter- and intramolecular versions of
      this process. The existence of concurrent inter- and intramolecular allylation
      reactions was demonstrated by deuteration experiments. While in the particular
      case at hand, we find very little difference in stereochemical outcome as one
      partitions between the inter- and intramolecular pathways, the techniques
      employed are applicable to other systems.

PMID- 16417395
TI  - Synthesis and properties of a new kinetically stabilized digermyne: new insights
      for a germanium analogue of an alkyne.
AB  - The reduction of an overcrowded (E)-1,2-dibromodigermene, Bbt(Br)Ge=Ge(Br)Bbt (2)
      [Bbt = 2,6-bis[bis(trimethylsilyl)methyl]-4-[tris(trimethylsilyl)methyl]phenyl],
      with KC8 afforded a stable digermyne, BbtGe[triple bond]GeBbt (1). The Ge[triple
      bond]Ge triple-bond characters of 1 were revealed by the X-ray crystallographic
      analysis and spectroscopic studies (UV/vis and Raman spectra) together with
      theoretical calculations. The Ge[triple bond]Ge bond lengths of the two
      nonidentical molecules of 1 observed in the unit cell were shorter than that of
      the previously reported digermyne, Ar'Ge[triple bond]GeAr' (Ar' = 2,6-Dip2C6H3,
      Dip = 2,6-diisopropylphenyl).

PMID- 16417396
TI  - Hypofractionated stereotactic radiotherapy for low grade glioma at McGill
      University: long-term follow-up.
AB  - Small, well-defined, unresectable low-grade gliomas are attractive targets for
      stereotactic irradiation. Fractionated stereotactic irradiation of these targets
      has the theoretical benefit of increased normal tissue sparing beyond that
      provided by the physical characteristics of stereotactic radiosurgery. From July
      1987 to November 1992, 21 patients were treated for low-grade glioma at our
      institution using a hypofractionated regimen of stereotactic radiotherapy. All
      patients had well-circumscribed, < 40 mm tumors. No patient had had prior
      radiotherapy. All lesions were histologically proven WHO grade I or II glial
      tumors. Lesions involved sensitive brain structures and were deemed unresectable.
      A typical dose of 42 Gy was delivered in 6 fractions over a two-week period using
      rigid immobilization and a linac-based dynamic stereotactic radiosurgical
      technique. Patients had a median age of 23 years (9-74) and were predominantly
      female (60%). Median tumor diameter was 20 mm. With a median follow-up for living
      patients of 13.3 years, the actuarial 5, 10, and 15-year overall survival rates
      are 76%, 71%, and 63%, respectively. Treatment was acutely well tolerated
      although three patients experienced late post-therapy complications. Our results
      and those of 241 patients treated in nine other institutional series are
      reviewed. Despite some examples of favorable short-term outcomes, all reported
      series are highly selected and thus likely biased. The data regarding the use of
      SRS is limited and, in our opinion, insufficient to claim a clear therapeutic
      advantage to SRS in the initial management of low-grade glioma. Our own results
      with hypofractionated stereotactic radiotherapy are similar to those expected
      with standard therapy.

PMID- 16417397
TI  - Technical note: gold marker implants and high-frequency jet ventilation for
      stereotactic, single-dose irradiation of liver tumors.
AB  - With reference to radiosurgery of the liver, we describe techniques designed to
      solve the methodological problem of striking targets subject to respiratory
      motion with the necessary precision. Implanting a gold marker in the vicinity of
      the liver tumor was the first step in ensuring the reproducibility of the
      isocenter's position. An 18-karat gold rod measuring 1.9 x 3 mm was implanted
      approximately 2 cm from the edge of the tumor as this was displayed in the
      spiral, thin-slice CT with contrast media. Both the implantation of the marker
      and the required, CT-controlled biopsy of the liver tumor can be achieved
      simultaneously with the same puncture needle. The efficiency of high-frequency
      jet ventilation (HFJV) in neutralizing the targeted organ's respiratory motion
      during stereotactic single-dose irradiation was evaluated. The procedure was
      carried out on ten patients without any complications. In the time between
      treatment planning and irradiation (3 days), no significant marker migration was
      observable. In all cases, the gold marker (volume: 7.5 mm(3)) was readily
      observable in the treatment beam using portal imaging. HFJV provided reliable
      immobilization. The liver motion in each anesthetized patient was limited to
      under 3.0 mm in all directions. Thus, the correct field settings and target
      reproducibility were able to be analyzed and documented during the irradiation.
      The combination of marker and HFJV enables the determination of stereotactic
      coordinates directly related to the liver itself and, in this way, stereotactic
      radiation treatment of liver tumors is freed from the uncertainties involved in
      orientation to bony landmarks, in respiratory motion, and in changes of position
      in the stereotactic body frame. The method is feasible and can improve the
      accuracy of stereotactic body radiation therapy.

PMID- 16417398
TI  - Implementation of talairach atlas based automated brain segmentation for
      radiation therapy dosimetry.
AB  - Radiotherapy for brain cancer inevitably results in irradiation of uninvolved
      brain. While it has been demonstrated that irradiation of the brain can result in
      cognitive deficits, dose-volume relationships are not well established. There is
      little work correlating a particular cognitive deficit with dose received by the
      region of the brain responsible for the specific cognitive function. One obstacle
      to such studies is that identification of brain anatomy is both labor intensive
      and dependent on the individual performing the segmentation. Automatic
      segmentation has the potential to be both efficient and consistent. Brains2 is a
      software package developed by the University of Iowa for MRI volumetric studies.
      It utilizes MR images, the Talairach atlas, and an artificial neural network
      (ANN) to segment brain images into substructures in a standardized manner. We
      have developed a software package, Brains2DICOM, that converts the regions of
      interest identified by Brains2 into a DICOM radiotherapy structure set. The
      structure set can be imported into a treatment planning system for dosimetry. We
      demonstrated the utility of Brains2DICOM using a test case, a 34-year-old man
      with diffuse astrocytoma treated with three-dimensional conformal radiotherapy.
      Brains2 successfully applied the Talairach atlas to identify the right and left
      frontal, parietal, temporal, occipital, subcortical, and cerebellum regions.
      Brains2 was not successful in applying the ANN to identify small structures, such
      as the hippocampus and caudate. Further work is necessary to revise the ANN or to
      develop new methods for identification of small structures in the presence of
      disease and radiation induced changes. The segmented regions-of-interest were
      transferred to our commercial treatment planning system using DICOM and dose
      volume histograms were constructed. This method will facilitate the acquisition
      of data necessary for the development of normal tissue complication probability
      (NTCP) models that assess the probability of cognitive complications secondary to
      radiotherapy for intracranial and head and neck neoplasms.

PMID- 16417399
TI  - Expanding the therapeutic index of radiation therapy by combining in situ gene
      therapy in the treatment of prostate cancer.
AB  - The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation
      to be delivered with the least possible associated toxicity. However, the
      persistence of cancer (local recurrence after radiotherapy) despite these
      increased doses as well as distant failure suggesting the existence of micro
      metastases, especially in the case of higher risk disease, have underscored the
      need for continued improvement in treatment strategies to manage local and micro
      metastatic disease as definitively as possible. This has prompted the idea that
      an increase in the therapeutic index of radiotherapy might be achieved by
      combining it with in situ gene therapy. The goal of these combinatorial therapies
      is to maximize the selective pressure against cancer cell growth while minimizing
      treatment-associated toxicity. Major efforts utilizing different gene therapy
      strategies have been employed in conjunction with radiotherapy. We reviewed our
      and other published clinical trials utilizing this combined radio-genetherapy
      approach including their associated pre-clinical in vitro and in vivo models. The
      use of in situ gene therapy as an adjuvant to radiation therapy dramatically
      reduced cell viability in vitro and tumor growth in vivo. No significant
      worsening of the toxicities normally observed in single-modality approaches were
      identified in Phase I/II clinical studies. Enhancement of both local and systemic
      T-cell activation was noted with this combined approach suggesting anti-tumor
      immunity. Early clinical outcome including biochemical and biopsy data was very
      promising. These results demonstrate the increased therapeutic efficacy achieved
      by combining in situ gene therapy with radiotherapy in the management of local
      prostate cancer. The combined approach maximizes tumor control, both local
      regional and systemic through radio-genetherapy induced cytotoxicity and anti
      tumor immunity.

PMID- 16417401
TI  - Evaluations of the renal cell carcinoma model Caki-1 using a silicon based
      microvascular casting technique.
AB  - The vascular development of orthotopically grown human renal cell carcinoma (Caki
      1) was examined using a silicon based casting technique in nude mice. Images
      taken of these vascular casts showed Caki-1 tumors to be highly vascularized and
      invasive. The spread of the tumor within the cortex of the kidney revealed that
      Caki-1 recruits the kidney's own vasculature, destroying the functional glomeruli
      in the process. The loss of these glomeruli was further highlighted by the
      presence of enlarged glomeruli resulting from the development of super nephrons.
      Vessel size and density measurements were then made in this model. This was done
      using both computer-based and manual measurement methods. In the vessel size
      studies the computer-based method tended to overestimate the number of larger
      diameter vessels whereas the vessels density assessment showed good agreement
      between the two techniques. Nevertheless, both methods showed that Caki-1 tumors
      possessed a higher proportion of larger diameter vessels and a lower vessel
      density than normal kidney cortex. In summary, silicon based vascular casting
      proved to be a simple and effective tool for the study of tumor vasculature. In
      particular this technique could readily be used to examine the invasion of tumor
      into normal tissue. The computer-based technique for evaluating vessel number and
      vascular density was found to have merit in both normal and tumor tissues,
      particularly in the vascular density studies. However, in both settings this
      technique did tend to overestimate the number of larger diameter vessels.

PMID- 16417400
TI  - PET/CT in the evaluation of response to treatment of liver metastases from
      colorectal cancer with bevacizumab and irinotecan.
AB  - The present approach at our institution for the treatment of patients with
      colorectal (CRC) cancer and with liver metastases planned for metastasectomy is
      the neoadjuvant administration of Bevacizumab with Irinotecan based therapy.
      Metabolic imaging of tumor viability with 18F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET), and simultaneous anatomic localization provided by low
      dose non-enhanced computed tomography (CT), can be obtained in a combined
      modality FDG-PET/CT scan. The purpose of this study was to evaluate the possible
      contribution of FDG-PET/CT as a surrogate marker to evaluate treatment response
      of liver metastases in vivo. This is a retrospective evaluation of 18F-FDG PET
      and CT findings in the first seven consecutive patients. FDG-PET/CT scans were
      performed before the start of the neoadjuvant and after four cycles of therapy,
      just prior to surgery. Results were compared to concurrent contrast-enhanced CT,
      when required, and pathology. Response to treatment was determined according to
      RECIST size criteria obtained from data from thin (3-5mm) slice CT, and changes
      in uptake of 18F-FDG uptake on PET. A total of 20 liver lesions were evaluated in
      seven patients. Overall, 6/7 patients had favorable response to treatment, and
      only one had progression of disease. One patient was found to be inoperable at
      surgery. Biopsy was obtained in 1/4 lesions in this patient, while pathology was
      unable for the remaining three lesions. As such, pathologic validation of
      findings was available for 17/20 lesions. Complete response (CR) was evident on
      FDG-PET in 10/17 (58%) lesions, whereas only 4/17(23%) were deemed CR by CT.
      Similarly, only 1/17 (6%) lesion appeared stable by FDG-PET criteria, whereas
      three (18%) were termed stable disease (SD) according to size on CT. FDG-PET
      findings correlated better than CT with pathology, and were more indicative of
      pathology. Overall PET/CT correctly predicted necrosis at pathology in 70% vs.
      35% by CT. Our results suggest that 18F-FDG PET may be instrumental for
      predicting the pathologic response to Bevacizumab based therapy.

PMID- 16417402
TI  - Ultrasound: a chemotherapy sensitizer.
AB  - Chemotherapy plays a very important role in cancer treatment. However, there are
      still some barriers in the successful use of such therapies, mainly because of
      the adverse side effects of the anticancer agents and due to the development of
      chemoresistance. This paper focuses on the use of ultrasound to enhance
      chemotherapy and to overcome drug resistance. The action of many anticancer
      agents can be improved with the use of ultrasonic exposure either in vitro or in
      vivo. Drug resistance can be circumvented using ultrasound alone. Furthermore,
      the reversal attributable to chemoresistance modifiers, such as verapamil and PSC
      833, is augmented by ultrasound. Ultrasound-mediated chemosensitization is
      usually achieved via increasing intracellular drug accumulation, although other
      mechanisms are also involved. Ultrasound also can play a role in targeted
      chemotherapy, releasing anticancer chemicals directly and efficiently into the
      lesions. However, this promising modality has not been clinically adopted so far
      and the reasons are discussed.

PMID- 16417403
TI  - Serum proteomic pattern analysis for early cancer detection.
AB  - The ability of physicians to effectively treat and cure cancer is directly
      dependent on their ability to detect cancers at their early stages. The early
      detection of cancer has the potential to dramatically reduce mortality. Recently,
      the use of mass spectrometry to develop profiles of patient serum proteins has
      been reported as a promising method to achieve this goal. In this paper, we
      analyzed the ovarian cancer and prostate cancer data sets using support vector
      machine (SVM) to detect cancer at the early stages based on serum proteomic
      pattern. The results showed that SVM, in general, performed well on these two
      data sets, as measured by sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy. Linear kernel worked the best on ovarian
      cancer data with a sensitivity of 0.99 and an accuracy of 0.97, while polynomial
      kernel worked the best on prostate cancer data with a sensitivity of 0.79 and an
      accuracy of 0.82. When redial kernel was applied to either of the two data sets,
      all the samples were predicted as cancer samples, with a sensitivity of 1 and a
      specificity of 0. Furthermore, feature selection did not improve SVM performance.

PMID- 16417404
TI  - Protein profiling of bladder cancer using the 2D-PAGE and SELDI-TOF-MS technique.
AB  - Protein profiling is a promising tool for tumor characterization and the
      detection of tumor markers in bladder cancer. Techniques for 2-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) and surface-enhanced laser
      desorption/ionization with time-of-flight mass spectrometry (SELDI-TOF-MS) have
      improved; both were evaluated using bladder tumor tissue. Normal urothelium and
      pTa G2, pT1 G3, and >or=pT3 G3 tissues were obtained from the operating room and,
      after macrodissection, subjected to 2D-PAGE and to SELDI-TOF-MS ProteinChip. 2D
      PAGE gels expressed significantly different protein patterns for pTa G2 and pT3
      G3 tumors. pT1 G3 tumors showed expression profiles similar to those of the
      invasive tumors, with upregulation of galectin 3, gelsolin, villin 2, moesin, and
      annexin 6. Similarly, distinct protein peaks were detected for superficial and
      muscle-invasive urothelial cancers by SELDI-TOF-MS. Six of seven superficial pTa
      G2 tumors showed an intense peak at 6.7 and 10.1 kD, while invasive carcinomas
      showed an intense peak near 9.5 kD. No disturbing influence of surrounding tissue
      on the results was detected. It was shown that both techniques (2D-PAGE and
      ProteinChip) work well, and especially ProteinChip analysis seems promising for
      clinical application.

PMID- 16417405
TI  - Genetic signature of anthropogenic population collapse in orang-utans.
AB  - Great ape populations are undergoing a dramatic decline, which is predicted to
      result in their extinction in the wild from entire regions in the near future.
      Recent findings have particularly focused on African apes, and have implicated
      multiple factors contributing to this decline, such as deforestation, hunting,
      and disease. Less well-publicised, but equally dramatic, has been the decline in
      orang-utans, whose distribution is limited to parts of Sumatra and Borneo. Using
      the largest-ever genetic sample from wild orang-utan populations, we show strong
      evidence for a recent demographic collapse in North Eastern Borneo and
      demonstrate that this signature is independent of the mutation and demographic
      models used. This is the first demonstration that genetic data can detect and
      quantify the effect of recent, human-induced deforestation and habitat
      fragmentation on an endangered species. Because current demographic collapses are
      usually confounded by ancient events, this suggests a much more dramatic decline
      than demographic data alone and emphasises the need for major conservation
      efforts.

PMID- 16417406
TI  - Hem-1 complexes are essential for Rac activation, actin polymerization, and
      myosin regulation during neutrophil chemotaxis.
AB  - Migrating cells need to make different actin assemblies at the cell's leading and
      trailing edges and to maintain physical separation of signals for these
      assemblies. This asymmetric control of activities represents one important form
      of cell polarity. There are significant gaps in our understanding of the
      components involved in generating and maintaining polarity during chemotaxis.
      Here we characterize a family of complexes (which we term leading edge
      complexes), scaffolded by hematopoietic protein 1 (Hem-1), that organize the
      neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin
      homologous protein (WAVE)2 complex, which mediates activation of actin
      polymerization by Rac, is only one member of this family. A subset of these
      leading edge complexes are biochemically separable from the WAVE2 complex and
      contain a diverse set of potential polarity-regulating proteins. RNA interference
      mediated knockdown of Hem-1-containing complexes in neutrophil-like cells: (a)
      dramatically impairs attractant-induced actin polymerization, polarity, and
      chemotaxis; (b) substantially weakens Rac activation and phosphatidylinositol
      (3,4,5)-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5)
      tris-phosphate)/Rac/F-actin-mediated feedback circuit that organizes the leading
      edge; and (c) prevents exclusion of activated myosin from the leading edge,
      perhaps by misregulating leading edge complexes that contain inhibitors of the
      Rho-actomyosin pathway. Taken together, these observations show that versatile
      Hem-1-containing complexes coordinate diverse regulatory signals at the leading
      edge of polarized neutrophils, including but not confined to those involving
      WAVE2-dependent actin polymerization.

PMID- 16417407
TI  - Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in
      sepsis in humans.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a devastating
      complication of numerous underlying conditions, most notably sepsis. Although
      pathologic vascular leak has been implicated in the pathogenesis of ARDS and
      sepsis-associated lung injury, the mechanisms promoting leak are incompletely
      understood. Angiopoietin-2 (Ang-2), a known antagonist of the endothelial Tie-2
      receptor, was originally described as a naturally occurring disruptor of normal
      embryonic vascular development otherwise mediated by the Tie-2 agonist
      angiopoietin-1 (Ang-1). We hypothesized that Ang-2 contributes to endothelial
      barrier disruption in sepsis-associated lung injury, a condition involving the
      mature vasculature. METHODS AND FINDINGS: We describe complementary human,
      murine, and in vitro investigations that implicate Ang-2 as a mediator of this
      process. We show that circulating Ang-2 is significantly elevated in humans with
      sepsis who have impaired oxygenation. We then show that serum from these patients
      disrupts endothelial architecture. This effect of sepsis serum from humans
      correlates with measured Ang-2, abates with clinical improvement, and is reversed
      by Ang-1. Next, we found that endothelial barrier disruption can be provoked by
      Ang-2 alone. This signal is transduced through myosin light chain
      phosphorylation. Last, we show that excess systemic Ang-2 provokes pulmonary leak
      and congestion in otherwise healthy adult mice. CONCLUSIONS: Our results identify
      a critical role for Ang-2 in disrupting normal pulmonary endothelial function.

PMID- 16417408
TI  - Gene expression programs in response to hypoxia: cell type specificity and
      prognostic significance in human cancers.
AB  - BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response
      that has important roles in normal physiology and in many human diseases. A
      transcription factor, hypoxia-inducible factor (HIF), plays a central role in the
      hypoxia response; its activity is regulated by the oxygen-dependent degradation
      of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia
      responses, little is known about the variation in the global transcriptional
      response to hypoxia among different cell types or how this variation might relate
      to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the
      temporal changes in global transcript levels in response to hypoxia in primary
      renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle
      cells, and endothelial cells with DNA microarrays. The extent of the
      transcriptional response to hypoxia was greatest in the renal tubule cells. This
      heightened response was associated with a uniquely high level of HIF-1alpha RNA
      in renal cells, and it could be diminished by reducing HIF-1alpha expression via
      RNA interference. A gene-expression signature of the hypoxia response, derived
      from our studies of cultured mammary and renal tubular epithelial cells, showed
      coordinated variation in several human cancers, and was a strong predictor of
      clinical outcomes in breast and ovarian cancers. In an analysis of a large,
      published gene-expression dataset from breast cancers, we found that the
      prognostic information in the hypoxia signature was virtually independent of that
      provided by the previously reported wound signature and more predictive of
      outcomes than any of the clinical parameters in current use. CONCLUSIONS: The
      transcriptional response to hypoxia varies among human cells. Some of this
      variation is traceable to variation in expression of the HIF1A gene. A gene
      expression signature of the cellular response to hypoxia is associated with a
      significantly poorer prognosis in breast and ovarian cancer.

PMID- 16417411
TI  - Chronic disease-related behaviors in U.S. older women: Behavioral Risk Factor
      Surveillance System, 2003.
AB  - OBJECTIVES: To estimate the prevalence of selected behaviors related to chronic
      diseases among women > or =65 years old using the 2003 Behavioral Risk Factor
      Surveillance System (BRFSS) data. METHODS AND RESULTS: Seven behaviors were
      assessed: having a healthy weight, current cigarette smoking status, consumption
      of at least five fruits or vegetables daily, leisure time physical activity in
      the the past month, moderate-to-vigorous physical activity during the average
      week, influenza immunization in the past year, and lifetime pneumococcal
      immunization. With increasing age, women > or =65 years old were more likely to
      have a healthy weight, to be a nonsmoker, and to consume at least five fruits or
      vegetables daily and less likely to participate in any leisure time or moderate
      to-vigorous physical activities. Women with higher incomes and educational
      attainment were more likely to engage in most healthful behaviors and to have a
      healthy weight. However, black non-Hispanic women were less likely than white
      women or those of other race or ethnicity to engage in most healthful behaviors
      and to have a healthy weight. Women who rated their health as fair or poor were
      more likely to receive a pneumococcal immunization, and those who rated their
      health as excellent were least likely to receive an influenza immunization in the
      past year. CONCLUSIONS: BRFSS data can be used to monitor the prevalence of
      behaviors related to chronic disease of women aged > or =65 years and to develop
      programs and polices that promote and reinforce healthful behaviors. These
      measures have the potential to help reduce morbidity and morality from chronic
      disease in older women, thereby minimizing the discrepancy between years of
      healthy life expectancy and life expectancy.

PMID- 16417412
TI  - Toward optimal health: Daniel Hanley, M.D. discusses issues of stroke management
      in women. Interviewed by Jodi R Godfrey.

PMID- 16417414
TI  - Cross-sectional association between markers of inflammation and serum sex steroid
      levels in the postmenopausal estrogen/progestin interventions trial.
AB  - BACKGROUND: Standard risk factors do not adequately capture cardiovascular risk
      in postmenopausal women. We sought to determine the associations between levels
      of sex steroids and levels of inflammatory markers in postmenopausal women.
      METHODS: We analyzed baseline data from a subset of postmenopausal women aged 45
      64 years who had stored samples during a randomized controlled trial. We measured
      levels of C-reactive protein (CRP), interleukin-6 (IL-6), matrix
      metalloproteinase-9 (MMP-9), soluble intercellular adhesion molecule (sICAM), and
      circulating sex steroids. Multiple linear regression models were created with
      each of the following hormone levels as the primary exposure variable: estrone,
      total estradiol, bioavailable estradiol, total testosterone, bioavailable
      testosterone, progesterone, and sex hormone-binding globulin (SHBG).
      Sociodemographic and lifestyle covariates were derived from standardized self
      report questionnaires and direct measurement (weight, height). RESULTS: Mean age
      of the 623 women was 56 years. After adjustment for age, body mass index (BMI),
      physical activity, alcohol consumption, and smoking, the bioavailable
      testosterone level (p = 0.03) was positively and the SHBG level (p < 0.001) was
      negatively associated with the logCRP level. The increment in CRP level between
      the highest and lowest quartile of bioavailable testosterone was 1.28 microg/mL.
      The increment in CRP level between the lowest and highest quartile of SHBG was
      2.62 microg/mL. Compared with SHBG or bioavailable testosterone as predictors of
      logCRP in separate regression models, when both SHBG and bioavailable
      testosterone were included in the same multivariate linear regression model, only
      SHBG remained a statistically significant predictor of logCRP. Progesterone level
      was positively associated with the logMMP-9 level (p < 0.001); no other sex
      steroid level was associated with the logMMP-9 level. In multiply adjusted
      models, no association was found between levels of any sex steroid and IL-6 or
      sICAM level.

PMID- 16417409
TI  - Associations among race/ethnicity, ApoC-III genotypes, and lipids in HIV-1
      infected individuals on antiretroviral therapy.
AB  - BACKGROUND: Protease inhibitors (PIs) are associated with hypertriglyceridemia
      and atherogenic dyslipidemia. Identifying HIV-1-infected individuals who are at
      increased risk of PI-related dyslipidemia will facilitate therapeutic choices
      that maintain viral suppression while reducing risk of atherosclerotic diseases.
      Apolipoprotein C-III (apoC-III) gene variants, which vary by race/ethnicity, have
      been associated with a lipid profile that resembles PI-induced dyslipidemia.
      However, the association of race/ethnicity, or candidate gene effects across
      race/ethnicity, with plasma lipid levels in HIV-1-infected individuals, has not
      been reported. METHODS AND FINDINGS: A cross-sectional analysis of
      race/ethnicity, apoC-III/apoA-I genotypes, and PI exposure on plasma lipids was
      performed in AIDS Clinical Trial Group studies (n = 626). Race/ethnicity was a
      highly significant predictor of plasma lipids in fully adjusted models.
      Furthermore, in stratified analyses, the effect of PI exposure appeared to differ
      across race/ethnicity. Black/non-Hispanic, compared with White/non-Hispanics and
      Hispanics, had lower plasma triglyceride (TG) levels overall, but the greatest
      increase in TG levels when exposed to PIs. In Hispanics, current PI
      antiretroviral therapy (ART) exposure was associated with a significantly smaller
      increase in TGs among patients with variant alleles at apoC-III-482, -455, and
      Intron 1, or at a composite apoC-III genotype, compared with patients with the
      wild-type genotypes. CONCLUSIONS: In the first pharmacogenetic study of its kind
      in HIV-1 disease, we found race/ethnic-specific differences in plasma lipid
      levels on ART, as well as differences in the influence of the apoC-III gene on
      the development of PI-related hypertriglyceridemia. Given the multi-ethnic
      distribution of HIV-1 infection, our findings underscore the need for future
      studies of metabolic and cardiovascular complications of ART that specifically
      account for racial/ethnic heterogeneity, particularly when assessing candidate
      gene effects.

PMID- 16417415
TI  - Waist circumference predicts cardiometabolic and global Framingham risk among
      women screened during National Woman's Heart Day.
AB  - PURPOSE: To evaluate the cardiometabolic risk profiles of 6938 women (mean age
      49.2 +/- 14.6 years) attending the 2005 Sister to Sister: Everyone Has a Heart
      Foundation free public health standardized cardiovascular disease (CVD) risk
      factor screening events in 12 cities across the United States by race/ethnicity
      and waist circumference. MAIN FINDINGS: Among women without a history of CVD or
      diabetes (n = 6327), 90% were found to have at least one major modifiable CVD
      risk factor, with one-third of women having three or more major risk factors.
      Nearly half of all women with elevated total cholesterol (> or = 200 mg/dL) or
      low high-density lipoprotein (HDL)-cholesterol (< 50 mg/dL) did not report a
      known history of abnormal cholesterol. Among women with no history of
      hypertension, 16% had a blood pressure > or = 140/90 mm Hg. Unrecognized diabetes
      and glucose intolerance were striking among fasting women (n = 1218; 9% had a
      blood glucose > or = 126 mg/dL and 43% had a blood glucose > or = 100 mg/dL). In
      adjusted logistic regression models, women with a waist circumference > or = 35
      inches were more likely to have blood pressure > or = 140/90 (OR = 1.9, p <
      0.0001), total cholesterol > or = 200 mg/dL (OR = 1.2, p = 0.006), HDL
      cholesterol < 50 mg/dL (OR = 2.5, p < 0.0001), fasting glucose > or = 100 mg/dL
      (OR = 2.0, p < 0.0001), and Framingham global risk score > or = 10%, CVD or
      diabetes (OR = 2.0, p < 0.0001). Waist circumference was significantly correlated
      with Framingham global risk (r = 0.24, p < 0.001) and number of risk factors (r =
      0.24, p < 0.0001). Increased clustering of risk factors was predictive of waist
      size > or = 35 inches vs. < 35 inches in logistic models (p for trend > 0.0001).
      Among a subsample of women who underwent standardized screening for stress and
      depression, 62% had stress levels associated with increased cardiac risk, and 27%
      met criteria for clinical depression. CONCLUSIONS: Hypertension, dyslipidemia,
      and/or impaired fasting glucose were newly identified in approximately half the
      women screened. Waist size significantly correlated with clustering of risk
      factors, global Framingham risk score, CVD and diabetes, suggesting it may be an
      easily measured surrogate for women at increased risk of future cardiovascular
      clinical events who may benefit from further assessment and intervention.

PMID- 16417416
TI  - Hormone therapy and coronary heart disease: the role of time since menopause and
      age at hormone initiation.
AB  - BACKGROUND: Apparently discrepant findings have been reported by the Women's
      Health Initiative (WHI) trial compared with observational studies of
      postmenopausal hormone therapy (HT) and coronary heart disease (CHD). METHODS: We
      prospectively examined the relation of HT to CHD, according to timing of hormone
      initiation relative to age and time since menopause. Participants were
      postmenopausal women in the Nurses' Health Study, with follow-up from 1976 to
      2000. Information on hormone use was ascertained in biennial, mailed
      questionnaires. We used proportional hazards models to calculate multivariable
      adjusted relative risks (RR) and 95% confidence intervals (CI). We also conducted
      sensitivity analyses to determine the possible influence of incomplete capture of
      coronary events occurring shortly after initiation of HT. RESULTS: Women
      beginning HT near menopause had a significantly reduced risk of CHD (RR = 0.66,
      95% CI 0.54-0.80 for estrogen alone; RR = 0.72, 95% CI 0.56-0.92 for estrogen
      with progestin). In the subgroup of women demographically similar to those in the
      WHI, we found no significant relation between HT and CHD among women who
      initiated therapy at least 10 years after menopause (RR = 0.87, 95% CI 0.69-1.10
      for estrogen alone; RR = 0.90, 95% CI 0.62-1.29 for estrogen with progestin).
      Among women who began taking hormones at older ages, we also found no relation
      between current use of estrogen alone and CHD (for women aged 60+ years, RR =
      1.07, 95% CI 0.65-1.78), although there was a suggestion of possible reduced risk
      for combined HT (RR = 0.65, 95% CI 0.31-1.38). In sensitivity analyses, we found
      that the incomplete capture of coronary events occurring shortly after initiation
      of HT could not explain our observation of a reduced risk of coronary disease for
      current users of HT. CONCLUSIONS: These data support the possibility that timing
      of HT initiation in relation to menopause onset or to age might influence
      coronary risk.

PMID- 16417417
TI  - Self-reported physical activity and myocardial flow reserve in postmenopausal
      women at risk for cardiovascular disease.
AB  - BACKGROUND: Regular exercise protects against coronary heart disease (CHD) events
      and improves vascular reactivity. Exercise effects on myocardial flow reserve
      (MFR) are not well studied. METHODS: We performed dynamic N-13 ammonia positron
      emission tomography (PET) in 16 postmenopausal women (60 +/- 6 years) to measure
      myocardial blood flow (MBF) and MFR. We also obtained information from each woman
      on her self-reported physical activity. RESULTS: Of the 16 patients, 6 reported
      moderate regular physical activity, and 10 did not. Women who reported regular,
      at least moderate physical activity had a higher percentage increase in adenosine
      MBF from rest compared with women who did not exercise (268% vs. 129%, p = 0.04)
      and had a significantly higher mean maximal MFR (3.68 vs. 2.29, p = 0.04).
      CONCLUSIONS: These findings provide further mechanistic support for the
      beneficial cardiovascular effects of exercise.

PMID- 16417418
TI  - Coronary heart disease and postmenopausal hormone therapy: conundrum explained by
      timing?

PMID- 16417419
TI  - Limitations of current cardiovascular disease risk assessment strategies in
      women.

PMID- 16417420
TI  - Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the
      role of SSRIs.
AB  - The hallmark feature of premenstrual syndrome (PMS) and premenstrual dysphoric
      disorder (PMDD) is the predictable, cyclic nature of symptoms or distinct
      on/offness that begins in the late luteal phase of the menstrual cycle and remits
      shortly after the onset of menstruation. PMDD is distinguished from PMS by the
      severity of symptoms, predominance of mood symptoms, and role dysfunction,
      particularly in personal relationships and marital/family domains. Several
      treatment modalities are beneficial in PMDD and severe PMS, but the selective
      serotonin reuptake inhibitors (SSRIs) have emerged as first-line therapy. The
      SSRIs can be administered continuously throughout the entire month,
      intermittently from ovulation to the onset of menstruation, or semi
      intermittently with dosage increases during the late luteal phase. These
      guidelines present practical treatment algorithms for the use of SSRIs in women
      with pure PMDD or severe PMS, PMDD and underlying subsyndromal clinical features
      of mood or anxiety, or premenstrual exacerbation of a mood/anxiety disorder.

PMID- 16417422
TI  - Menopausal Vasomotor Symptoms (MVS) survey for assessment of hot flashes.
AB  - OBJECTIVES: During the menopause, 65%-80% of women experience hot flashes. Hot
      flashes can also occur after hysterectomy and may be experienced during cancer
      therapy. A very limited assessment of hot flashes is provided by currently
      available menopausal instruments. This study was performed to evaluate a new
      Menopausal Vasomotor Symptoms (MVS) survey as an instrument for a comprehensive
      and subjective assessment of hot flashes. METHODS: The MVS survey was designed to
      assess multiple dimensions of hot flashes and to be simple and easy to
      administer. Hot flashes and associated conditions were addressed with 39 closed
      ended questions. Sixty-one qualified women, 40-58 years old, from the Dallas,
      Fort Worth Metroplex area were enrolled. Women experiencing hot flashes took the
      survey at baseline and then 14 days, 2 months, and 6 months later. Factor
      analysis was performed. Face and content validity, internal consistency, test
      retest reliability, and sensitivity to changes were evaluated. RESULTS: Fifty-two
      women (85.2%) completed all study sessions. The MVS survey was found to have good
      face and content validity and good internal consistency (rhoKR = 0.87). Spearman
      rank-order correlation coefficients at the 14-day retest varied from 0.58 to
      1.00. As a result of these analyses, the MVS survey was further refined.
      CONCLUSIONS: The MVS survey was found to be comprehensive, simple, valid,
      reliable, sensitive, and a convenient instrument for subjective assessment of
      various characteristics of hot flashes. The MVS survey may serve as a valuable
      clinical and research tool for measurement of hot flashes.

PMID- 16417421
TI  - Social support and prenatal alcohol use.
AB  - BACKGROUND: Lack of social support during pregnancy may be associated with the
      prenatal use of alcohol. The purpose of this study is to evaluate the degree,
      predictors, and consequences of social support in a cohort of 200 pregnant women
      who scored 2 or more on the T-ACE, a 4-item screening questionnaire for prenatal
      drinking. METHODS: The pregnant women completed the Maternal Social Support Index
      (MSSI). Their partners completed the same measure, which was modified to reflect
      their status as the biological fathers. RESULTS: Despite having similar overall
      MSSI scores, there was only slight to fair agreement on the level of support
      received by the pregnant women for most daily tasks when their responses were
      compared with their partners. Predictors of increased maternal social support
      included the woman's being married and having more education and a more
      prestigious job than her partner. Social support was not predictive of either
      subsequent prenatal alcohol use or newborn birth weight. CONCLUSIONS: Regardless
      of social support, previous, prepregnancy, and early pregnancy drinking were the
      most predictive factors for subsequent prenatal alcohol consumption in this
      sample, underscoring the importance of screening pregnant women for drinking.

PMID- 16417423
TI  - Effect of relationship factors on safer sex decisions in older inner-city women.
AB  - OBJECTIVES: Heterosexual transmission of the human immunodeficiency virus (HIV)
      in older women is on the rise, yet little is known about safer sex practices in
      these women. We sought to determine the prevalence of and effect of relationship
      factors on safer sex practices among older women living in a high HIV incidence
      region. METHODS: In a cross-sectional study at an ambulatory medicine clinic of a
      large inner-city hospital, participants were women over age 50 seeking medical
      services at the study site. Measurements included (1) partner trust, (2)
      dependence on partner, (3) personally obtaining condoms, (4) safer sex (frequent
      condom use or abstinence), (5) knowledge of condom efficacy, and (6) perceived
      HIV risk. RESULTS: Of 155 participants in a current relationship, 81% were
      sexually active; however, only 13% of these women used condoms frequently. No
      significant differences were found between participants who did and did not
      practice safer sex with respect to their age, race, employment, marital status,
      knowledge of condom efficacy, or perceived HIV risk. Trust in partner was
      independently associated with lower odds of safer sex (OR 0.3, 95% CI 0.08-1.06).
      Personally obtaining condoms (OR 9.2, 95% CI 1.9-44.2) and dependence on partner
      for condoms (OR 12.3, 95% CI 3.0-50.3) were independently associated with higher
      odds of safer sex. CONCLUSIONS. Few older women in high HIV incidence areas
      practice safer sex. Relationship factors impact the risk of acquiring HIV through
      safer sex decisions. HIV prevention messages geared to older women should
      incorporate references to the role these factors can play in reducing their HIV
      risk.

PMID- 16417424
TI  - Cancer incidence among female flight attendants: a meta-analysis of published
      data.
AB  - BACKGROUND: Flight attendants are exposed to cosmic ionizing radiation and other
      potential cancer risk factors, but only recently have epidemiological studies
      been performed to assess the risk of cancer among these workers. The aim of the
      present work was to evaluate the incidence of various types of cancer among
      female cabin attendants by combining cancer incidence estimates reported in
      published studies. METHODS: All follow-up studies reporting standardized
      incidence ratio (SIR) for cancer among female flight attendants were obtained
      from online databases and analyzed. A metaanalysis was performed by applying
      Bayesian hierarchical models, which take into account studies that reported SIR =
      0 and natural heterogeneity of study-specific SIRs. RESULTS: A total of seven
      published studies reporting SIR for several cancer types were extracted. Meta
      analysis showed a significant excess of melanoma (meta-SIR 2.15, 95% posterior
      interval [PI] 1.56-2.88) and breast carcinoma (meta-SIR 1.40; PI 1.19-1.65) and a
      slight but not significant excess of cancer incidence across types (meta-SIR
      1.11, PI 0.98-1.25). CONCLUSIONS: Although further studies are necessary to
      clarify the exact role of occupational exposure, all airlines should, as some
      companies do, estimate radiation dose, organize the schedules of crew members in
      order to reduce further exposure in highly exposed flight attendants, inform crew
      members about health risks, and give special protection to pregnant women.

PMID- 16417426
TI  - Fluctuating rodent populations and risk to humans from rodent-borne zoonoses.
AB  - The fluctuations in abundance of a wildlife reservoir are an attractive
      explanation for temporal variation in primary human cases of a zoonosis. This is
      because high abundance may lead to more contact between humans and animals, but
      also to outbreaks of disease within the reservoir population. We propose a
      mathematical framework that sets out the consequences of correlation between
      reservoir abundance and reservoir prevalence for how numbers of human cases are
      related to reservoir abundance. The fluctuations of rodent populations are well
      studied and often dramatic. A review of field studies of rodent reservoirs for
      plague, hantaviruses, and other zoonoses shows that, at a seasonal time scale, a
      positive correlation between host abundance and host prevalence is rarely
      observed. More commonly, there is an inverse relationship or negative correlation
      such that a seasonal increase in rodent abundance is not accompanied by a
      corresponding increase in the abundance of infectious animals. Seasonal changes
      in rodent abundance are hence unlikely to fully explain seasonal variation in
      primary human cases. The few longer field studies (>5 years) show a positive but
      delayed relationship between reservoir abundance and reservoir prevalence.

PMID- 16417427
TI  - Habitat factors associated with bank voles (Clethrionomys glareolus) and
      concomitant hantavirus in northern Sweden.
AB  - Puumala virus (PUUV), genus hantavirus, causes nephropathia epidemica, a mild
      form of hemorrhagic fever with renal syndrome in humans. In this study, bank
      voles, the natural reservoir of PUUV, were captured at locations of previous
      human PUUV exposure and paired controls within a region of high incidence in
      northern Sweden. The aim of the study was to evaluate the influence of
      environmental factors on the abundance of bank voles and the occurrence of PUUV.
      The total number of voles and the number of PUUV-infected voles did not differ
      between locations of previous human PUUV exposure and paired controls. The number
      of bank voles expressing antibodies to PUUV infection increased linearly with
      total bank vole abundance implying density independent transmission. Using
      principal component and partial correlation analysis, we found that particular
      environmental characteristics associated with old-growth moist forests (i.e.,
      those dominated by Alectoria spp., Picea abies, fallen wood, and Vaccinium
      myrtillus) were also associated with increased abundance of bank vole and hence
      the number of PUUV-infected bank voles, whereas there were no correlations with
      factors associated with dry environments (i.e., Pinus sylvestris and V. vitis
      idea). This suggests that circulation and persistence of PUUV within bank vole
      populations was influenced by habitat factors. Future modeling of risk of
      exposure to hantavirus and transmission of PUUV within vole populations should
      include the influence of these factors.

PMID- 16417428
TI  - Immunological responses and the pattern of disease in mice infected with
      transfected Leishmania major constitutively expressing active IL-1alpha.
AB  - Immunity against leishmaniasis is mediated mainly by CD4+ T lymphocytes, which
      function by secreting cytokines, which in turn activate various effector
      mechanisms. Interleukin 1 (IL-1) represents one of the most pleiotropic
      proinflammatory cytokines and is required for normal regulation of Th1/Th2
      responses. The aim of this study was to induce the expression of the inflammatory
      cytokine IL-1alpha by Leishmania parasites and to determine its effect on the
      parasite development. Leishmania constitutively producing IL-1alpha was
      engineered, using the pX63Hyg-IL-1alpha vector. IL-1alpha was produced by both
      promastigotes and amastigotes, and remained unchanged after transformation and
      development in mice. The protection against the disease achieved in BALB/c mice
      by the transfected parasites was superior to that obtained with the wild type.
      One month after infection a nodule was demonstrated in 22% and 60% of the mice
      inoculated with transfected parasites and the wild type, respectively. This
      tendency continued for an additional 2.5 months, after which the rate of
      infection increased to 90% and 100% in these two groups, respectively. The
      present study suggests that, during initial infection, the pathway of IL-1alpha
      production and its accessibility to the immunological cells might be important in
      the outcome of leishmanial infection.

PMID- 16417429
TI  - Genetic divergence of rabies viruses from bat species of Colorado, USA.
AB  - Molecular epidemiological studies have linked many cryptic human rabies cases in
      the United States with exposure to rabies virus (RV) variants associated with
      insectivorous bats. In Colorado, bats accounted for 98% of all reported animal
      rabies cases between 1977 and 1996. The genetic divergence of RV was investigated
      in bat and terrestrial animal specimens that were submitted for rabies diagnosis
      to the Colorado Department of Public Health and Environment (CDPHE), Colorado,
      USA. RV isolates from animal specimens across the United States were also
      included in the analysis. Phylogenetic analyses were performed on partial
      nucleoprotein (N) gene sequences, which revealed seven principal clades. RV
      associated with the colonial big brown bat, Eptesicus fuscus, an bats of the
      genus Myotis were found to segregate into two distinct clades (I and IV). Clade I
      was harbored by E. fuscus and Myotis species, but was also identified in
      terrestrial animals such as domestic cats and striped skunks (Mephitis mephitis).
      Clade IV was divided into subclades IVA, IVB, and IVC; IVA was identified in E.
      fuscus, and Myotis species bats, and also in a fox; subclades IVB and IVC
      circulated predominantly in E. fuscus. Clade II was formed by big free-tailed bat
      (Nyctinomops macrotis) and striped skunk (Mephitis mephitis) samples. Clade III
      included RVs that are maintained by generally solitary, migratory bats such as
      the silver-haired bat (Lasionycteris noctivagans) and bats of the genus Lasiurus.
      Big brown bats were found to harbor this RV variant. None of the Colorado
      specimens segregated with clades V and VII that harbor RVs associated with
      terrestrial animals. Different species of bats had the same RV variant,
      indicating active inter-species rabies transmission. In Colorado, animal rabies
      occurs principally in bats, and the identification of bat RVs in cat, gray fox
      Urocyon cinereoargenteus), and striped skunks demonstrated the importance of
      rabies spillover from bats to domestic and terrestrial wildlife species.

PMID- 16417430
TI  - Eastern cottontail rabbits (Sylvilagus floridanus) develop West Nile virus
      viremias sufficient for infecting select mosquito species.
AB  - The potential of the eastern cottontail rabbit (CTR; Sylvilagus floridanus) to
      contribute to an enzootic West Nile virus (WNV) cycle was demonstrated by
      characterizing the WNV viremia profile of 15 CTRs and demonstrating that
      mosquitoes could become infected by feeding on these CTRs. Eight CTRs were
      infected with a titer of 10(5.0) cell-infectious dose 50% endpoints (CID50s) of
      WNV (NY99-Crow) by needle and seven CTRs by bite of one or more WNV-infected
      mosquitoes. There were no marked differences between the WNV viremia profiles of
      CTRs infected by either method. West Nile virus was detected in serums of all
      CTRs by 24 h p.i. The daily mean titers of all 15 CTRs on days 1-4 p.i. were
      10(4.1+/-0.4), 10(4.7+/-0.3), 10(4.1+/-0.6), and 10(3.7+/-0.6) respectively,
      declining to 10(1.2+/-0.1) CID50s/ml of serum by day 6 p.i. No virus was detected
      in the blood of any CTR on day 7 p.i. The average duration of WNV titers of
      >or=10(4.3) and <10(5.0) CID50s/mL for all CTRs was 2.2 +/- 0.6 and 1.0 +/- 0.1
      days, respectively. The minimum estimated infection rates (MEIRs) of Culex
      pipiens (L.) and Culex salinarius (Coq.) that fed on CTRs with titers of
      >or=10(4.3) and >10(5.0) were 11.5 +/- 5.5 and 21 +/- 6.0%, respectively. These
      rates increased to 20.5 +/- 6.4% and 25.0 +/- 3.0% when CTR serum titers were
      >10(5.0) CID50s/mL. Neither Aedes aegypti (L.) nor Aedes albopictus (Skuse) were
      infected by feeding on CTRs with titers of <10(5.0) CID50s/mL. The MEIRs of these
      two species were 11.5 +/- 3.5% and 1.5 +/- 0.5% after feeding on CTRs with titers
      of >10(5.0) CID50s/ml. None of the CTRs infected by mosquito bite or by needle
      showed any symptoms of WNV disease.

PMID- 16417432
TI  - Experimental infection models of ticks of the Rhipicephalus sanguineus group with
      Rickettsia conorii.
AB  - Rhipicephalus sanguineus group ticks collected on dogs in Thailand were
      maintained in the laboratory over several generations to test methods to infect
      these ticks with Rickettsia conorii, the agent of Mediterranean spotted fever.
      Three methods were tested: (1) infection of adults and nymphs through
      artificially induced bacteremic rabbit, (2) capillary feeding of solution
      containing 5 x 10(3) and 5 x 10(5)pfu/mL of R. conorii to adult female ticks, and
      (3) immersion of engorged nymphs which were "one leg-cut," "two leg-cut," or
      "cuticle cut" in solution containing R. conorii. The most efficient method to
      infect adult ticks with R. conorii was infection of ticks through the bacteremic
      rabbit (71.4%). The best method to infect nymphs with R. conorii was immersion of
      "one leg-cut" engorged nymphs in solution containing R. conorii (30%).
      Interestingly, a high mortality of the ticks infected with R. conorii was
      observed regardless of the method used. The harmful effect of R. conorii on Rh.
      sanguineus group ticks from Thailand is discussed including the role of the
      geographic origin of the ticks and the difficulties to identify ticks within this
      group to the species level.

PMID- 16417431
TI  - Evidence of tick-borne organisms in mule deer (Odocoileus hemionus) from the
      western United States.
AB  - Free-ranging mule deer (MD; Odocoileus hemionus) from Arizona and California were
      tested for evidence of infection with several tick-borne pathogens, including
      species of Ehrlichia, Anaplasma, Babesia, and Borrelia. Of 125 mule deer tested
      from Arizona, 29 (23%) and 11 (9%) had antibodies reactive to E. chaffeensis and
      A. phagocytophilum by indirect immunofluorescent antibody testing, respectively;
      none of the six MD tested from California were seropositive. Using a commercial
      competitive ELISA kit, antibodies reactive to Anaplasma spp. were detected in 19
      (15%) MD from Arizona and four of six (67%) MD from California. Polymerase chain
      reaction (PCR) testing for tick-borne pathogens was conducted on blood samples
      from 29 MD from Arizona and 11 MD from California. Twenty-two of 29 (75.9%) MD
      from Arizona had PCR evidence of infection with at least one tick-borne pathogen.
      We detected an Anaplasma sp. in 19 of 29 (65.5%) MD and a Babesia sp. in 10 of 29
      (34%) MD. Sequencing of these amplicons indicated that the Anaplasma sp. was the
      same that had previously been detected in MD from California and the Babesia sp.
      was similar to one previously detected in a reindeer (Rangifer tarandus tarandus)
      from California. All of the California MD had evidence of infection with a tick
      borne pathogen. Two different species of Anaplasma spp. were detected in MD from
      California, eight of of 11 MD were infected with an Anaplasma sp., and three of
      11 MD were infected with A. ovis. This is the first report of a mule deer
      naturally infected with A. ovis. Ten of 11 MD from California were infected with
      a Babesia-like organism previously associated with human disease, and a single MD
      was PCR positive for Borrelia coriaceae, which has been associated with epizootic
      bovine abortion. Together, these data suggest that MD in northern Arizona and
      eastern California are exposed to several pathogens of human and veterinary
      importance.

PMID- 16417433
TI  - West Nile virus in host-seeking mosquitoes within a residential neighborhood in
      Grand Forks, North Dakota.
AB  - West Nile virus (WNV) was first recovered in North Dakota near the city of Grand
      Forks in June 2002. During 2002, 2003, and 2004, we collected mosquitoes from
      Grand Forks using Mosquito Magnet traps and tested them for WNV. The seasonal
      abundance, species composition, and reproductive status of female mosquitoes were
      correlated with local environmental temperature and state surveillance data on
      WNV to determine the factors affecting local transmission of WNV. Over 90% of the
      mosquitoes collected were Aedes vexans, Ochlerotatus dorsalis, and Culex
      tarsalis, but WNV was detected only in Cx. tarsalis. Average summertime
      temperatures and relative abundance of mosquitoes were highest in 2002 but no WNV
      positive mosquitoes were detected until the following summer. In 2003,
      nulliparous Cx. tarsalis appeared in mid-June (first summer brood), and parous
      Cx. tarsalis appeared in mid-July. The first WNV-positive pool occurred 21 July,
      and minimum daily infections rates increased thereafter until 27 August. The
      minimum infection rate (MIR) for Cx. tarsalis during the season was 5.7 infected
      mosquitoes per 1,000 tested, with the highest infection rates occurring at the
      end of the season as Cx. tarsalis populations started to decline. Mid-to-late
      August was identified as the period of highest risk for being bitten by a WNV
      infected mosquito in Grand Forks during 2003. In 2004, viral activity in Grand
      Forks was low, due to very cool temperatures throughout the summer. To examine
      the genetic diversity of the 2003 WNV isolates from Grand Forks, we sequenced a
      366-nucleotide region of the capsid and premembrane gene. Thirteen (46%) of the
      28 WNV isolates contained at least one nucleotide substitution when compared to
      the homologous region of the progenitor WN NY-99 strain, and seven of these 13
      substitutions coded for amino acid changes. Thus, WNV is established in North
      Dakota, it appears to be evolving and it is vectored primarily by Cx. tarsalis.

PMID- 16417434
TI  - Distribution of borreliae among ticks collected from eastern states.
AB  - Lyme disease is the most commonly reported vector-borne disease in the United
      States and is transmitted by Borrelia burgdorferi-infected Ixodes species. The
      disease is typically characterized by an erythema migrans (EM) rash at the site
      of tick feeding. EM rashes have also been associated with feeding by Amblyomma
      americanum ticks despite evidence suggesting that they are incompetent vectors
      for Lyme disease. In 1996, a Borrelia organism only recently cultivated in the
      laboratory was described in A. americanum ticks and designated B. lonestari. This
      Borrelia is believed to be the etiologic agent of a novel Lyme-like disease,
      southern tick associated rash illness (STARI). This study examined ticks
      collected from eight eastern states to evaluate the epidemiology of B. lonestari,
      B. burgdorferi, and their tick hosts. Three hundred individual or small pool
      samples were evaluated from tick genera that included Amblyomma, Ixodes, and
      Dermacentor. DNA was extracted following tick homogenization and the polymerase
      chain reaction (PCR) was performed using primers derived from the flagellin gene
      that amplify sequences from both B. burgdorferi and B. lonestari. Species
      specific digoxigenin labeled probes were designed and used to differentiate
      between B. burgdorferi and B. lonestari. Borrelia DNA was detected in
      approximately 10% of the A. americanum and I. scapularis tick samples, but none
      was present in any of the Dermacentor samples tested. Positive samples were
      detected in ticks collected from Kentucky, Maryland, Massachusetts, New Jersey,
      New York, and Virginia. This is the first known report of B. lonestari from
      Massachusetts and New York and the first detection in I. scapularis. This
      suggests that B. lonestari and its putative association with STARI may be more
      widespread than previously thought.

PMID- 16417435
TI  - Potential vertebrate reservoir hosts and invertebrate vectors of Anaplasma
      marginale and A. phagocytophilum in central Spain.
AB  - Organisms in the genus Anaplasma are obligate intracellular pathogens that
      multiply in both vertebrate and invertebrate hosts. The type species, A.
      marginale, causes bovine anaplasmosis and only infects ticks and ruminants. A.
      phagocytophilum causes human and animal granulocytic anaplasmosis, and
      genetically closely related strains show a wide host range, including ticks,
      ruminants, rodents, equids, canids, birds, and humans. Recent reports
      demonstrated that A. marginale and A. phagocytophilum co-exist in geographic
      areas and that concurrent infections occur in ruminants and ticks. In this study,
      we characterized A. marginale and A. phagocytophilum infections in wild and
      domestic animals, and ticks collected in central Spain by serology, PCR, and
      sequence of 16S rRNA genotypes. Species tested included humans, cattle, dogs,
      rodents, Iberian red deer, European wild boar, birds, and ticks. Species of
      hematophagous Diptera were analyzed as potential mechanical vectors of Anaplasma
      spp. A. marginale was detected in tabanids, ticks, cattle, and deer, while A.
      phagocytophilum was detected in ticks, deer, cattle, and birds. Concurrent
      infections of the two Anaplasma were found in cattle and deer. These results
      illustrate the complexity of the epizootiology of A. marginale and A.
      phagocytophilum in regions where both pathogens co-exist and share common
      reservoir hosts and vectors. The increasing contact between wildlife, domestic
      animals, and human populations increases the risk of outbreaks of human and
      bovine anaplasmosis, and the difficulty of implementing surveillance and control
      measures.

PMID- 16417436
TI  - Rodent-associated Bartonella in Saskatchewan, Canada.
AB  - Six species of wild rodents were sampled at 10 sites in 2002 and 2003 to
      determine the prevalence of Bartonella infections in rodent communities near
      Saskatoon, Saskatchewan, Canada. Isolates were characterized genotypically and
      compared with isolates found at other locations. Of 104 wild rodents examined,
      57% were infected with Bartonella and prevalence within species varied from 49%
      for Richardson's ground squirrels (Spermophilus richardsonii) to 90% for
      Franklin's ground squirrels (S. franklinii). Infected rodents were found at all
      sites. Sequencing of a 379-bp portion of the citrate synthase gene was performed
      on 54 isolates and revealed 13 distinct genotypes, eight of which had not been
      described previously. The most common genotype detected in red-backed voles
      (Clethrionomys gapperi) was 99.1% similar to B. grahamii, a known human pathogen.
      Two of 10 Franklin's ground squirrels were concurrently infected with multiple
      Bartonella genotypes. All genotypes, with the exception of one detected in both
      Franklin's and thirteen-lined ground squirrels (S. tridecemlineatus), were found
      in only one host, and all genotypes from each species, with the exception of
      genotypes detected in red-backed voles, clustered together within the same
      relatedness group, suggesting that at least some Bartonella genotypes are
      specific to some rodent hosts.

PMID- 16417437
TI  - West Nile virus in Southern Portugal, 2004.
AB  - West Nile virus (WNV) genomic RNA was detected by reverse transcription
      polymerase chain reaction (RT-PCR) in six out of 57 mosquito pools collected in
      Southern Portugal, during the summer of 2004, yielding an infection rate (IR) of
      2.8/1,000 mosquitoes. Phylogenetic analysis of a 217-nucleotide fragment of the
      NS5 coding region, amplified from Culex pipiens s.l. and Culex univittatus unfed
      females, demonstrated a close relationship with WNV strains circulating in the
      Mediterranean basin (Italy, 1998; France, 2000; Morocco, 2003). The data in this
      short report demonstrate the presence of WNV in mosquitoes in Southern Portugal
      and the need of permanent surveillance for viral activity within the country.

PMID- 16417438
TI  - Interview with Robert K. Washino, Ph.D. Interview by Vicki Glaser.

PMID- 16417439
TI  - PooledInfRate software.

PMID- 16417441
TI  - Can immunonutrients reduce rejection rates in African Americans?
AB  - OBJECTIVES: African-American kidney allograft recipients have higher rates of
      rejection than do white patients. This study was performed to determine whether
      the use of immunonutrients may reduce the incidence of rejection in African
      Americans. MATERIALS AND METHODS: Two studies have been done at our institution
      that demonstrate that immunonutrients can reduce the incidence of rejection,
      calcineurin inhibitor toxicity, and cardiovascular risk factors. The data were
      analyzed to determine whether or not a preferential benefit exists for race.
      RESULTS: Twenty-four African-American patients received supplements and 28 did
      not. One patient (4.2%) who had received supplements had a rejection episode in
      the first year compared with 7 patients (25%) who did not receive supplements (P
      < .011). This compares with our rejection rate of 25% (14/56) for African
      Americans on other protocols without concurrent immunonutrients (P < .003).
      CONCLUSIONS: Immunonutrients appear to have a preferential beneficial response in
      reducing rejection in African-American patients. A randomized, prospective,
      clinical trial is warranted to further elucidate these results.

PMID- 16417442
TI  - Transplant tourism and the Iranian model of renal transplantation program:
      ethical considerations.
AB  - Currently, the buying and selling of kidneys through "transplant tourism" is
      occurring at an increasing rate, both in developed and developing countries.
      Since 1988, Iran has adopted a compensated and regulated living-unrelated donor
      renal transplant program, and by providing financial incentives to volunteer
      living donors, has eliminated the renal transplant waiting list. In the Iranian
      model of renal transplantation program, regulations have been put in place to
      prevent transplant tourism. Foreigners are not allowed to undergo renal
      transplantation from Iranian living-unrelated donors. They also are not permitted
      to volunteer as kidney donors for Iranian patients. A study at the transplant
      unit of Hashemi Nejad Kidney Hospital in Tehran, Iran, showed that of 1881 renal
      transplant recipients, 19 (1%) were Afghani or Iraqi refugees, 11 (0.6%) were
      other foreign nationals, and 18 (0.9%) were Iranian immigrants. Renal
      transplantations seemed ethically acceptable to all refugees and foreign
      nationals. However, transplantation of Iranian immigrants who had been residing
      abroad for years constituted true transplant tourism.

PMID- 16417443
TI  - Mycophenolic acid plasma trough level: correlation with clinical outcome.
AB  - OBJECTIVES: Assess the relationship between clinical diagnosis, state of
      immunosuppression, mycophenolic acid (MPA) plasma trough levels (MPACmin), and
      mycophenolate mofetil (MMF) dosage in renal transplant recipients. MATERIALS AND
      METHODS: MPACmin were determined in 30 kidney transplant patients, of whom 7
      exhibited biopsy-proven acute rejection. The remaining 23 had normal graft
      function. Graft outcome, defined by clinical diagnosis and serum creatinine
      level, was compared according to MPACmin, MMF dosage, and total lymphocyte count
      (LC). RESULTS: Patients with acute rejection had similar MPACmin (2.4 +/- 1.7
      microg/mL), MMF dosages (1.7 +/- 0.5 g), and LCs (0.001165 +/- 0.0040 x 10(9)/L)
      when compared with normal patients (2.2 +/- 0.7 microg/mL, 1.7 +/- 0.4 g and
      0.001160 +/- 0.00527 x 10(9)/L) respectively. Rejection rates were comparable
      irrespective of MPACmin)ranges and higher in those receiving the 1-g dose (30%)
      when compared with those receiving 1.5-g and 2-g doses (12.5% and 11.7%). No
      relationship was observed between MPACmin and MMF doses, and neither parameter
      correlated with LC. CONCLUSIONS: These results suggest that MPACmin is a poor
      correlate of clinical outcome and state of immunosuppression. Although the
      usually recommended dosage of MMF (2 g) may be associated with acute rejection,
      low-dose MMF (1 g) seems to constitute a higher risk.

PMID- 16417444
TI  - Intravenous mycophenolate mofetil with low-dose oral tacrolimus and steroid
      induction for live donor liver transplantation.
AB  - OBJECTIVES: Mycophenolate mofetil (MMF) is used in liver transplantation (LTx) to
      reduce rejection, nephrotoxicity, neurotoxicity, and the need for steroids. Lower
      trough concentrations and bioavailability have been reported with oral MMF in
      first week after LTx. These parameters improve after the first month
      postoperatively. Previously published studies have used oral formulations of MMF.
      In this study, we sought to examine survival, rejection, and nephrotoxicity rates
      using IV MMF in live donor liver transplantation (LDLT). PATIENTS AND METHODS:
      Twenty-eight patients (mean age, 50.1 years; 15 men, 13 women) were examined
      between January 2000 and January 2004 with a mean follow-up of 17 months for
      survival, rejection, and renal function. RESULTS: Four patients died at 2, 5, 8,
      and 18 months after LDLT from sepsis (n = 3) and recurrent hepatocellular
      carcinoma (n = 1). There were no retransplants; hence, patient and graft survival
      rates were the same (82.4%). Three patients (10.7%) experienced acute cellular
      rejection requiring treatment. The mean serum creatinine level prior to LDLT was
      0.9 +/- 0.4 mg/dL, which remained stable throughout the study. One patient
      required hemodialysis during the perioperative period for 8 days. CONCLUSIONS: In
      the current study, we demonstrate a new strategy of IV MMF administration with
      low-dose tacrolimus that provides for lower rates of acute rejection, better
      preservation of renal function, and one that is better tolerated compared with
      historical treatments after LTx.

PMID- 16417445
TI  - Complete regression of visceral Kaposi's sarcoma after conversion to sirolimus.
AB  - The prevalence of Kaposi's sarcoma (KS) is much greater in organ transplant
      recipients than it is in the general population. Its etiology appears to be
      related to geographic, genetic, and viral factors. Treatment of transplant
      related KS has, until now, consisted mainly of reduction of, or withholding of,
      immunosuppression, often with deleterious effects on both graft and patient
      survival. In recent years, the immunosuppressive drug, sirolimus, has been
      demonstrated as possessing anti-neoplastic properties in both in vitro and animal
      models. In view of these properties and some preliminary clinical experience, we
      postulated that sirolimus would be beneficial in our patients who developed
      transplant-related KS. Here, we report the first case of a patient with both
      cutaneous and visceral KS who was successfully treated in the Middle East by
      conversion from a cyclosporine-based to a sirolimus-based immunosuppression
      regimen. The KS regressed completely within a few months after the conversion.
      The chronologic events and the extensive documentation, which included repeat
      computed tomography scans, are very suggestive of a selective anti-neoplastic
      effect of sirolimus.

PMID- 16417446
TI  - In vitro influence of polyclonal anti-thymocyte globulins on leukocyte expression
      of adhesion molecules.
AB  - OBJECTIVES: Polyclonal anti-thymocyte globulins (ATGs) are drugs used in the
      induction of immunosuppression, in the treatment of acute rejection, and in the
      therapy of hematologic disorders. Treatment with ATGs can produce adverse effects
      due to cross-reacting antibodies directed against nonmyeloid cells. This study
      sought to evaluate the interaction of ATGs and some adhesion molecules expressed
      on the surface of neutrophils and lymphocytes. MATERIALS AND METHODS: We
      determined the effects of different doses of 3 polyclonal ATGs on the activation
      and expression of lymphocyte and neutrophil adhesion molecules in whole blood by
      means of flow cytometry. RESULTS: ATG treatment reduced the percentage of
      lymphocytes gated for CD18 and CD62L, as well as the expression of CD11b, CD18,
      and CD62L in a dose-dependent manner. ATGs modulated the percentage of gated
      neutrophils for CD18. Although ATG treatment did not affect CD11b or CD62L gating
      in neutrophils, it did regulate expression of these adhesion markers.
      CONCLUSIONS: Our results show that ATGs can modify the expression levels of some
      of the main leukocyte adhesion molecules that are responsible for the
      characteristic cellular adhesion after ischemia/ reperfusion. These properties of
      ATGs may contribute to reduced leukocyte infiltration after solid-organ
      transplantation.

PMID- 16417447
TI  - The effect of machine perfusion on the arteries of porcine kidneys.
AB  - OBJECTIVES: Machine perfusion is an excellent method of assessing the viability
      of a kidney graft and can also potentially improve the quality of an equivocal
      kidney. Several authors have expressed concerns that machine perfusion can
      potentially damage the vessels of the kidney but until now, no studies have been
      performed to clarify this issue. We aimed to examine the effect of machine
      perfusion on the renal arteries of porcine kidneys. MATERIALS AND METHODS: Eight
      pairs of kidneys were removed from pigs in the abattoir. One kidney of each pair
      was preserved on ice for 24 hours. The other kidney from the same animal was
      initially stored on ice until arrival at the laboratory when it was perfused on
      the RM3 machine for 4 hours and then stored again on ice for the remainder of the
      24 hours. After 24 hours, since the retrieval and initial storage on ice at the
      abattoir, tissue samples were obtained from all renal arteries at 3 different
      sites. These samples were sent for histologic evaluation. RESULTS: Machine
      perfusion caused more damage at a statistically significant level compared with
      simple cold storage only for the first sample site, which was the part of the
      renal artery closest to the perfusion cannula. CONCLUSIONS: Our experiments
      suggest that machine perfusion, even when it is done lege artis, can damage the
      part of the renal artery closest to the adaptor, which can potentially result in
      a higher incidence of posttransplant arterial thrombosis. Therefore, excision of
      the first part of the renal artery should be considered prior to transplantation,
      and modifications of the perfusion technique must be developed to minimize damage
      to the renal arteries.

PMID- 16417448
TI  - Novel treatment with rituximab of oropharyngeal posttransplant
      lymphoproliferative disorder after heart transplantation.
AB  - Posttransplant lymphoproliferative disorders are severe complications that arise
      after solid organ transplantation, which are often related to Epstein- Barr
      virus. Reports are anecdotal, and a standardized therapy does not exist. We
      report a case of a 36-year-old man who developed posttransplant
      lymphoproliferative disorder of the oropharynx 1 year after receiving a heart
      transplant. A short review of the literature is presented, after which a new
      therapeutic approach that combines antiviral therapy, monoclonal antibodies, and
      a sirolimus-based maintenance immunosuppression regimen with reduced target
      trough levels of tacrolimus is introduced. The patient achieved complete
      remission and was free from recurrence 18 months after the therapy was initiated.

PMID- 16417449
TI  - Fungal infections in solid organ recipients.
AB  - BACKGROUND: Fungal infections are a major cause of morbidity and mortality after
      organ transplantation. The incidence of these infections has increased
      considerably over the last decade. OBJECTIVES: The aim of this study was to
      evaluate the incidence of fungal infections, to identify the most common fungal
      pathogens, and to determine the associated risk factors in solid organ
      recipients. METHODS: One hundred twenty renal and 50 liver recipients were
      transplanted at the organ transplant unit of Nemazi Hospital in Shiraz, Iran,
      from September 2004 to August 2005 and were followed for fungal infections for at
      least 6 months. On admission to the hospital, all patients were evaluated for
      fungal colonization by mouth, vagina, urine, and rectal swabs cultured in
      Sabouraud Dextrose Agar. Samples of sputum, bronchoalveolar lavage, urine,
      cerebrospinal fluid (CSF), pleural tap, and tissue biopsy were evaluated by
      direct microscopic examination and were cultured for any clinical signs of fungal
      infections. RESULTS: Fifty-four kidney recipients (45%) had Candida colonization
      in different sites of their bodies. Fungal infections presented in 13 of 120
      recipients (10.8%). Five recipients had invasive fungal infections (3 had fungal
      pneumonitis and 2 had severe esophagitis), and 8 patients had cutaneous and
      mucocutaneous infections. All of the recipients with invasive fungal infections
      were colonized with Candida, and 2 of them died. Forty-two (84%) liver recipients
      had Candida colonization in different sites of their bodies. Fungal infections
      presented in 6 liver recipients. In 4 patients, invasive fungal infections
      occurred (2 fungal pneumonitis, 1 meningitis, and 1 severe esophagitis), 2
      patients showed mucocutaneous infections. Three recipients with invasive fungal
      infections had Candida colonization. The mean time to diagnosis was 70 days after
      transplantation. The most common etiologic agent for fungal infections was
      Candida albicans. CONCLUSIONS: Renal and liver recipients with Candida
      colonization are at high risk for fungal infections and therefore, control of
      fungal colonization in liver and renal transplant candidates would reduce the
      risk of invasive fungal infections after transplantation.

PMID- 16417450
TI  - Successful ABO-incompatible liver transplantation with pre- and postoperative
      plasmapheresis, triple immunosuppression, and splenectomy for fulminant hepatic
      failure.
AB  - Fulminant hepatic failure continues to be a challenge to hepatologists and
      surgeons. Because of the rapid deterioration in the clinical condition of
      patients with fulminant hepatic failure and the scarcity of available grafts, an
      ABO-incompatible liver donor may be the only choice for a patient with life
      threatening hepatic insufficiency. Here, we report a patient with fulminant
      hepatic failure who received an ABO-incompatible liver transplantation who was
      treated with pre- and posttransplantation double-volume total plasma exchange,
      splenectomy, and triple immunosuppression (tacrolimus, mycophenolate mofetil, and
      prednisone) in July 2003. At 26 months' follow-up, the patient's postoperative
      course has been uneventful. Using protocols aimed at removing existing
      isohemagglutinins and reducing further antibody production, ABO-incompatible
      liver transplantation may be performed as a life-saving procedure in patients
      with fulminant hepatic failure.

PMID- 16417451
TI  - WASP family proteins act between cytoskeleton and cellular signaling pathways.
AB  - This review considers the proteins of the WASP (Wiskott-Aldrich syndrome protein)
      family and their role in the regulation of actin-based motility. It contains
      detailed classification of the WASP family proteins and data on their subcellular
      localization. Impairments of expression of the WASP family proteins cause certain
      cell pathologies. The review also deals with domain organization of these
      proteins and proteins interacting with various domains of the WASP proteins.
      Special attention is given to analysis of the role of the WASP family proteins in
      initiating directed actin assembly in the leading edge of the migrating cell and
      on the surface of some bacteria. Putative pathways of regulation of WASP proteins
      by various protein ligands and their links with cell signaling systems are
      considered.

PMID- 16417452
TI  - Immunology of apoptosis and necrosis.
AB  - A complex of reactions regulating the number of cells in organs and tissues under
      normal and pathologic conditions is one of the most important systems of
      multicellular organisms. In this system, which controls both cell proliferation
      and clearance, clearance has been given special attention during the last three
      decades. Some stages of the clearance are known (the choice of "unwanted" cells,
      their destruction not affecting the surrounding tissue, and, finally, removal of
      the corpses), and undeniable progress has been achieved in the understanding of
      the second stage mechanisms, whereas mechanisms of elimination per se of cells or
      their fragments still continue to be terra incognita. The clearance of such cells
      is mainly determined by different components of natural and adaptive immunity:
      phagocytes, complement, opsonins, antigen-presenting cells, etc. Recently
      specific "danger signals", such as hydrolases, DNA, heat shock proteins, and
      other potential immunogens released by cells during their elimination have been
      discovered. Entering the extracellular space, these signals induce inflammation
      and injury of the surrounding tissues, i.e., autoimmune reactions. Heat shock
      proteins, in addition to chaperon activity, act as signaling, costimulating, and
      antigen-carrying molecules in the interactions of dying cells and the immune
      system.

PMID- 16417453
TI  - Effect of enzyme preparation from the marine mollusk Littorina kurila on fucoidan
      from the brown alga Fucus distichus.
AB  - A fucoidanase preparation from the marine mollusk Littorina kurila cleaved some
      glycosidic bonds in fucoidan from the brown alga Fucus distichus, but neither
      fucose nor lower oligosaccharides were produced. The main product isolated from
      the incubation mixture was a polysaccharide built up of disaccharide repeating
      units -->3)-alpha-L-Fucp-(2,4-di-SO3(-))-(1-->4)-alpha-L-Fucp-(2SO3(-))-(1-->,
      the structure coinciding with the idealized formula proposed for the initial
      substance. A polymer fraction with the same carbohydrate chain but sulfated only
      at positions 2 and nonstoichiometrically acetylated at positions 3 and 4 of
      fucose residues was isolated as a minor component. It is suggested that the
      native polysaccharide should contain small amounts of non-sulfated and non
      acetylated fucose residues, and only their glycosidic bonds are cleaved by the
      enzyme. The enzymatic hydrolysis showed that irregular regions of the native
      polysaccharide containing acetylated and partially sulfated repeating units were
      assembled in blocks.

PMID- 16417454
TI  - Use of modified flap structures for study of base excision repair proteins.
AB  - To investigate interactions between proteins participating in the long-patch
      pathway of base excision repair (BER), DNA duplexes with flap strand containing
      modifications in sugar phosphate backbone within the flap-forming
      oligonucleotides were designed. When the flap-forming oligonucleotide consisted
      of two sequences bridged by a decanediol linker located in the flap strand near
      the branch point, the efficiency and position of cleavage by flap endonuclease 1
      (FEN1) differed from those for natural flap. The cleavage rate of chimeric
      structure by FEN1 was lower than that of a normal substrate. When we introduced
      the second modification in the flap-forming oligonucleotide, the cleavage rate
      decreased significantly. To estimate efficiency of recognition and processing of
      the chimeric structures by BER proteins, we studied the rate of DNA synthesis by
      DNA polymerase beta (Pol beta) and the rate of nucleotide excision at the 3'-end
      of the initiating primer by apurinic/apyrimidinic endonuclease 1 (APE1) compared
      with those for the natural DNA duplexes. Efficiency of strand-displacement DNA
      synthesis catalyzed by Pol beta was shown to be higher for flap structures
      containing non-nucleotide linkers. The chimeric structures were processed by the
      3'-exonuclease activity of APE1 with efficiency lower than that for a normal flap
      structure. Thus, DNA duplexes with modifications in sugar phosphate backbone can
      be used to mimic intermediates of the long-patch pathway of BER in reconstituted
      systems containing FEN1. Based on chimeric and natural oligonucleotides,
      photoreactive DNA structures were designed. The photoreactive dCMP moiety was
      introduced into the 3'-end of DNA primer via the activity of Pol beta. The
      photoreactive DNA duplexes--3'-recessed DNA, nicked DNA, and flap structures
      containing natural and chimeric oligonucleotides--were used for photoaffinity
      labeling of BER proteins.

PMID- 16417455
TI  - Changes in superoxide dismutase activity and peroxynitrite content in rat
      peritoneal macrophages exposed to He-Ne laser radiation.
AB  - The formation of reactive oxygen and nitrogen species by rat peritoneal
      macrophages induced by a low-intensity He-Ne laser radiation (LR) was studied in
      this work. It was found that the formation of reactive oxygen species, nitric
      oxide, and peroxynitrite as well as changes in the activity of superoxide
      dismutase (SOD) depended to a large extent on the LR dose. In particular, it was
      found that activation of SOD at low LR doses was accompanied by nitric oxide
      level increase, while the level of peroxynitrite showed no significant changes.
      On the other hand, an enhanced LR dose inhibited the enzyme, and this was
      accompanied by peroxynitrite accumulation. All the measurements were carried out
      the day after LR treatment. The revealed regularities consequently demonstrate
      the existence of a deferred LR action on macrophages associated with the
      production of reactive oxygen and nitrogen species.

PMID- 16417456
TI  - Functional expression and properties of Sec14p-like protein with molecular mass
      45 kD from rat olfactory epithelium.
AB  - cDNA of Sec14p-like water-soluble protein with molecular mass 45 kD from rat
      olfactory epithelium was expressed in Escherichia coli Rosetta cells. The
      expression product was purified by a two-step chromatographic procedure on DEAE
      Sepharose and Sephacryl S-200. The identity of structural and functional
      characteristics of the recombinant and native proteins was demonstrated by CD,
      mass spectrometry, and Western blotting. Using several lipids immobilized on
      nitrocellulose membranes, it was shown that phosphatidylinositol-3,4,5
      triphosphate is the specific ligand for the studied protein.

PMID- 16417457
TI  - Electrogenic protonation of the secondary quinone acceptor Q(B) in spinach
      photosystem II complexes incorporated into lipid vesicles.
AB  - The generation of transmembrane electric potential difference (delta psi) in
      quinone acceptor complex of proteoliposomes containing core complexes of
      photosystem II from spinach was studied using for the measurements a direct
      electrometric technique. Besides the fast increase in the membrane potential
      associated with the electron transfer between the redox-active tyrosine 161
      residue (Y(Z)) in D1 polypeptide and the primary quinone acceptor Q(A), an
      additional electrogenic phase with tau approximately 0.85 msec at pH 7.3 and the
      maximal relative amplitude of approximately 11% of the Y(Z)ox Q(A)- phase was
      observed after the second light flash. The sensitivity of this phase to diuron
      (an inhibitor of electron transfer between Q(A) and the secondary quinone
      acceptor Q(B)), the dependence of its amplitude on the light flash parity, and
      also a decrease in its rate constant with increase in pH indicated that it was
      due to dismutation of Q(A)- and Q(B)- with the subsequent protonation of a doubly
      reduced plastoquinone molecule: Q(A)- Q(B)- + 2H+ --> Q(A)Q(B)H2.

PMID- 16417458
TI  - Functional coupling between nucleoside diphosphate kinase of the outer
      mitochondrial compartment and oxidative phosphorylation.
AB  - In rat liver mitochondria all nucleoside diphosphate kinase of the outer
      compartment is associated with the outer surface of the outer membrane (Lipskaya,
      T. Yu., and Plakida, K. N. (2003) Biochemistry (Moscow), 68, 1136-1144). In the
      present study, three systems operating as ADP donors for oxidative
      phosphorylation have been investigated. The outer membrane bound nucleoside
      diphosphate kinase was the first system tested. Two others employed yeast
      hexokinase and yeast nucleoside diphosphate kinase. The two enzymes exhibited the
      same activity but could not bind to mitochondrial membranes. In all three
      systems, muscle creatine phosphokinase was the external agent competing with the
      oxidative phosphorylation system for ADP. Determination of mitochondrial
      respiration rate in the presence of increasing quantities of creatine
      phosphokinase revealed that at large excess of creatine phosphokinase activity
      over other kinase activities (of the three systems tested) and oxidative
      phosphorylation the creatine phosphokinase reaction reached a quasi-equilibrium
      state. Under these conditions equilibrium concentrations of all creatine
      phosphokinase substrates were determined and K(eq)app of this reaction was
      calculated for the system with yeast hexokinase. In samples containing active
      mitochondrial nucleoside diphosphate kinase the concentrations of ATP, creatine,
      and phosphocreatine were determined and the quasi-equilibrium concentration of
      ADP was calculated using the K(eq)app value. At balance of quasi-equilibrium
      concentrations of ADP and ATP/ADP ratio the mitochondrial respiration rate in the
      system containing nucleoside diphosphate kinase was 21% of the respiration rate
      assayed in the absence of creatine phosphokinase; in the system containing yeast
      hexokinase this parameter was only 7% of the respiration rate assayed in the
      absence of creatine phosphokinase. Substitution of mitochondrial nucleoside
      diphosphate kinase with yeast nucleoside diphosphate kinase abolished this
      difference. It is concluded that oxidative phosphorylation is accompanied by
      appearance of functional coupling between mitochondrial nucleoside diphosphate
      kinase and the oxidative phosphorylation system. Possible mechanisms of this
      coupling are discussed.

PMID- 16417459
TI  - Purification and characterization of an intracellular beta-glucosidase from the
      methylotrophic yeast Pichia pastoris.
AB  - Pichia pastoris beta-glucosidase was purified to apparent homogeneity by salting
      out with ammonium sulfate, gel filtration, and ion-exchange chromatography with Q
      Sepharose and CM-Sepharose. The enzyme is a tetramer (275 kD) made up of four
      identical subunits (70 kD). The pH optimum is 7.3, and it is fairly stable in the
      pH range 5.5-9.5. The temperature optimum is 40 degrees C. The purified beta
      glucosidase is effectively active on p-/o-nitrophenyl-beta-D-glucopyranosides (p
      /o-NPG) and 4-methylumbelliferyl-beta-D-glucopyranoside (4-MUG) with Km values of
      0.12, 0.22, and 0.096 mM and Vmax values of 10.0, 11.7, and 6.2 micromol/min per
      mg protein, respectively. It also exhibits different levels of activity against p
      nitrophenyl-1-thio-beta-D-glucopyranoside, cellobiose, gentiobiose, amygdalin,
      prunasin, salicin, and linamarin. The enzyme is competitively inhibited by
      gluconolactone, p-/o-nitrophenyl-beta-D-fucopyranosides (p-/o-NPF), and glucose
      against p-NPG as substrate. o-NPF is the most effective inhibitor of the enzyme
      activity with Ki value of 0.41 mM. The enzyme is more tolerant to glucose
      inhibition with Ki value of 7.2 mM for p-NPG. Pichia pastoris has been employed
      as a host for the functional expression of heterologous beta-glucosidases and the
      risk of high background beta-glucosidase activity is discussed.

PMID- 16417460
TI  - Antioxidant status, alpha-amylase production, growth, and survival of hemoglobin
      bearing Escherichia coli exposed to hypochlorous acid.
AB  - In the present work, two matched strains of E. coli that bear a recombinant R
      amylase gene (MK57) or the R-amylase gene and vgb (MK79-hemoglobin expressing
      strain) were exposed to HOCl. In these cells, glutathione (GSH), superoxide
      dismutase (SOD), catalase (CAT), alpha-amylase production, growth and lethality
      were assessed in the presence and absence of HOCl. It was observed that the
      hemoglobin makes cells highly susceptible to killing by HOCl. The maximum
      survival for both strains was with stationary phase cells at any concentration of
      HOCl. Both strains grown in the presence of 0.0125-0.075 mg/liter HOCl showed a
      substantial increase in SOD activity and GSH level, with MK79 being the most
      increased strain in this respect, while the level of CAT activity was decreased
      in a dose depended manner. Growth of MK57 and MK79 strains decreased as HOCl
      concentration increased. However, HOCl at concentration above zero enhanced alpha
      amylase production (about 2-fold) in both MK79 and MK57. Furthermore, total
      amylase production (at all HOCl concentrations) by MK79 was always greater than
      that by MK57. The results indicate that except for survival, the hemoglobin helps
      cells to grow better and produces more recombinant products and activates general
      defense systems more in response to oxidative stress when compared with the non
      hemoglobin-containing counterpart.

PMID- 16417461
TI  - New theoretical schemes of the simplest chemical oscillators.
AB  - Based on the sufficient conditions for existence of concentration oscillations of
      the components of bicomponent reaction, all possible chemical reactions with two,
      three, or four intermediate stages proceeding via the mass-action expression are
      considered. About forty new schemes of chemical/biochemical oscillators are
      developed.

PMID- 16417462
TI  - Molecular weight and subunit composition of the sensitive to GABA-ergic ligands
      Cl-/HCO3(-)-stimulated Mg2+-ATPase from plasma membrane of rat brain.
AB  - The molecular weight and subunit composition of Cl-,HCO3(-)- and picrotoxin
      stimulated Mg2+-ATPase from rat brain plasma membrane solubilized in sodium
      deoxycholate were studied by gel filtration chromatography. The enzyme activity
      eluted from a Sephacryl S-300 column in a single peak associated with a protein
      of molecular weight approximately 300 kD and a Stokes radius of 5.4 nm. The
      enzyme-enriched fraction, concentrated and denatured by SDS, migrated through a
      Sephacryl S-200 column as three peaks with molecular weights of approximately 57,
      53, and 45 kD. SDS-PAGE also showed three major protein bands with molecular
      weights of about 57, 53, and 48 kD. The molecular weight and subunit composition
      of the Cl- and HCO3(-)-stimulated Mg2+-ATPase from neuronal membrane of rat brain
      are similar with the molecular properties of GABA(A)-benzodiazepine receptor
      complex from mammalian brain but are different from those of P-type transport
      ATPases.

PMID- 16417463
TI  - Effects of dark adaptation on light-induced electron transport through
      photosystem I in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - Kinetics of the redox reactions in the reaction center (P700) of photosystem I
      (PSI) of the cyanobacterium Synechocystis sp. PCC 6803 have been studied by EPR
      spectroscopy. The redox kinetics were recorded based on accumulation of the EPRI
      signal when the final signal was the sum of individual signals produced in
      response to illumination of the cells. After prolonged (more than 3 sec) dark
      intervals between illuminations, the kinetic curve of the EPR signal from P700+
      was multiphasic. After a sharp increase in the signal amplitude at the beginning
      of illumination (phase I), the amplitude rapidly (for 0.1-0.2 sec) decreased
      (phase II). Then the signal amplitude gradually increased (phase III) until the
      steady rate of electron transfer was established. With short-term (1 sec) dark
      intervals between the flashes and also in the presence of 3-(3,4-dichlorophenyl)
      1,1-dimethylurea (DCMU), the kinetics of the light-induced increase in the EPR
      signal from P700+ were monophasic. Inhibition with iodoacetamide of electron
      transport on the acceptor side of PSI under anaerobic conditions or an increase
      in the amount of respiration substrates on addition of glucose into a suspension
      of DCMU-treated wild-type cells increased the level of P700 reduction in phase
      III. The findings suggest that the kinetic curve of the EPR signal from P700+ is
      determined by both the electron entrance onto P700+ on the donor side of PSI and
      activity of electron acceptors of PSI.

PMID- 16417464
TI  - Lipoxygenase pathway of arachidonic acid metabolism in growth control of tumor
      cells of different type.
AB  - The influence of inhibitors of different lipoxygenases (LOX) on the growth of
      human tumor cells with different profiles of synthesized eicosanoids was studied.
      The studied LOX inhibitors had virtually no influence on the growth of A549 cells
      actively synthesizing cyclooxygenase and lipoxygenase metabolites of arachidonic
      acid (AA). The inhibitor of 12-LOX, baicalein, significantly inhibited
      proliferation in cultures of A431 epidermoid carcinoma cells with a
      characteristic domination of the major lipoxygenase metabolite of AA, 12
      hydroxyeicosatetraenoic acid (12-HETE), in the profile of synthesized eicosanoids
      and reduced to 70% the incorporation of [3H]thymidine into DNA. Treatment of
      these cultures with 12-HETE virtually restored the growth potential of the tumor
      cells. The findings suggest that the lipoxygenase metabolite of AA, 12-HETE, is a
      growth-limiting factor for tumor cells of definite type.

PMID- 16417465
TI  - Small RNAs in human brain development and disorders.
AB  - Small RNA is a variable and abundant type of non-coding RNAs in brain. The
      function of these RNAs is mainly unknown. A specific class of small RNA,
      microRNA, is dynamically regulated in neurogenesis and in embryo brain
      development. The genes for synaptic formation and some mental retardation
      disorders are putative targets for microRNA predicted by computational
      algorithms. The molecular pathways for mental development, common forms of
      autisms, schizophrenia, and affective disorders have yet to be elucidated. The
      hypothesis proposed here is that small regulatory RNAs, specifically microRNAs,
      play a role in human brain development and pathogenesis of brain disorders,
      especially of neurodevelopmental conditions. Pilot tests using comprehensive
      arrays of microRNAs demonstrate that microRNAs derived from postmortem human
      brains are applicable for microRNA expression profiling. The abundant expression
      of many regulatory small RNAs in human brain implies their biological role that
      must be tested by functional assays in neurons and by genetic and comparative
      expression profiling.

PMID- 16417466
TI  - Endothelin-1 (ET-1) promotes MMP-2 and MMP-9 induction involving the
      transcription factor NF-kappaB in human osteosarcoma.
AB  - In the present study, we have investigated the effect of (i) ET-1 (endothelin-1)
      and its precursor, big ET-1, on MMP (matrix metalloproteinase)-2 and MMP-9
      synthesis and activity in osteosarcoma tissue, and (ii) ET-1 receptor antagonists
      on cell invasion. Using Western blotting, zymography, RT-PCR (reverse
      transcription-PCR), immunohistochemistry, immunofluorescence and Northern
      blotting, we have shown that ET-1 and ET-1 receptors (ET(A) and ET(B)) were
      expressed in these cells. Additionally, we have demonstrated that ET-1 markedly
      induced the synthesis and activity of MMP-2, which was significantly increased
      when compared with MMP-9. Furthermore, inhibition of NF-kappaB (nuclear factor
      kappaB) activation blocked MMP-2 production and activity, indicating the
      involvement of NF-kappaB, a ubiquitous transcription factor playing a central
      role in the differentiation, proliferation and malignant transformation. Since ET
      1 acts as an autocrine mediator through gelatinase induction and because
      inhibition of ET(A) receptor is beneficial for reducing both basal and ET-1
      induced osteosarcoma cell invasion, targeting this receptor could be an
      attractive therapeutic alternative for the successful treatment of osteosarcoma.

PMID- 16417467
TI  - Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple
      organ failure.
AB  - Novel therapies for the treatment of MOF (multiple organ failure) are required.
      In the present study, we examined the effect of synthetic GHRP-6 (growth hormone
      releasing peptide-6) on cell migration and proliferation using rat intestinal
      epithelial (IEC-6) and human colonic cancer (HT29) cells as in vitro models of
      injury. In addition, we examined its efficacy when given alone and in combination
      with the potent protective factor EGF (epidermal growth factor) in an in vivo
      model of MOF (using two hepatic vessel ischaemia/reperfusion protocols; 45 min of
      ischaemia and 45 min of reperfusion or 90 min of ischaemia and 120 min of
      reperfusion). In vitro studies showed that GHRP-6 directly influenced gut
      epithelial function as its addition caused a 3-fold increase in the rate of cell
      migration of IEC-6 and HT29 cells (P<0.01), but did not increase proliferation
      ([3H]thymidine incorporation). In vivo studies showed that, compared with
      baseline values, ischaemia/reperfusion caused marked hepatic and intestinal
      damage (histological scoring), neutrophilic infiltration (myeloperoxidase assay;
      5-fold increase) and lipid peroxidation (malondialdehyde assay; 4-fold increase).
      Pre-treatment with GHRP-6 (120 microg/kg of body weight, intraperitoneally) alone
      truncated these effects by 50-85% (all P<0.05) and an additional benefit was seen
      when GHRP-6 was used in combination with EGF (1 mg/kg of body weight,
      intraperitoneally). Lung and renal injuries were also reduced by these pre
      treatments. In conclusion, administration of GHRP-6, given alone or in
      combination with EGF to enhance its effects, may provide a novel simple approach
      for the prevention and treatment of MOF and other injuries of the
      gastrointestinal tract. In view of these findings, further studies appear
      justified.

PMID- 16417468
TI  - Forgotten and novel aspects in pancreas development.
AB  - Diseases related to the pancreas are of highest importance in public health. It
      is anticipated that a detailed understanding of the molecular events that govern
      the embryonic development of this organ will have an immediate impact on clinical
      research relating to this issue. One major aim is the reconstruction of embryonic
      development in vitro with appropriate precursor cells, a second strategy is aimed
      at understanding the transdifferentiation of non-pancreatic into pancreatic
      tissue, and a third avenue is defined by the stimulation of the intrinsic ability
      of the pancreas to regenerate. Recent progress in developmental biology with
      respect to these different topics is reviewed in the present article. In
      addition, we also address evolutionary aspects of pancreas development,
      emphasizing the role of the South African clawed frog, Xenopus laevis, as an
      additional useful model system to study the molecular control of pancreas
      development.

PMID- 16417469
TI  - Alternative trans-splicing: a novel mode of pre-mRNA processing.
AB  - Alternative splicing is an important process contributing to proteome diversity
      without involving an increase in the number of genes. In some cases, alternative
      splicing is carried out under 'trans-mode', called alternative trans-splicing, in
      which exons located on separate pre-mRNA molecules are selectively joined to
      produce mature mRNAs encoding proteins with distinct structures and functions.
      However, it is not known how widespread or how frequently trans-splicing occurs
      in vivo. Recently, trans-allelic trans-splicing has been unambiguously
      demonstrated in Drosophila using a SNP (single nucleotide polymorphism) as a
      marker. In this review, we provide an overview of alternative trans-splicing in
      Drosophila and mammals, and discuss its mechanisms.

PMID- 16417478
TI  - Molecules of the mind: integrating synaptic biochemistry to understand brain
      function.
AB  - The focused meeting entitled 'Molecular Determinants of Synaptic Function:
      Molecules and Models' brought together several molecules and experimental models
      that are furthering our understanding of the biochemical basis of integrative
      brain function. Invited speakers and short communications from more junior
      scientists highlighted how individual molecules or protein networks underlie
      defined subcellular functions (e.g. transmitter release, receptor activation and
      transmitter uptake) can be used to unravel integrative function at cellular,
      systems and behavioural levels.

PMID- 16417479
TI  - Gephyrin: does splicing affect its function?
AB  - Gephyrin is a protein involved in both synaptic anchoring of inhibitory ligand
      gated ion channels and molybdenum cofactor synthesis. Substantial progress has
      been made in understanding its gene and protein structures. Furthermore, numerous
      binding partners of gephyrin have been identified. The mechanisms by which these
      interactions occur are unclear at present. Alternative splicing has been proposed
      to contribute to gephyrin's functional diversity within single cells as well as
      in different cell types and tissues.

PMID- 16417480
TI  - GRIF-1-kinesin-1 interactions: a confocal microscopy study.
AB  - GRIF-1 [GABA(A) (gamma-aminobutyric acid(A)) receptor interacting factor-1] is a
      member of a coiled-coil family of proteins thought to function as adaptors in the
      anterograde trafficking of organelles utilizing the kinesin-1 motor proteins to
      synapses. To study in more detail the molecular interaction between GRIF-1 and
      the kinesin-1 family member KIF5C, fluorescent yellow- and fluorescent cyan
      tagged GRIF-1, KIF5C, the KIF5C MD (motor domain) and the KIF5C NMD (non-motor
      domain) fusion proteins were generated. Each was characterized with respect to
      size and ability to co-associate by immunoprecipitation following expression in
      HEK-293 (human embryonic kidney 293) cells. Further, their distribution in
      transfected HEK-293 and transformed African green monkey kidney (COS-7) cells was
      analysed by confocal microscopy. The fluorescent GRIF-1 and KIF5C fusion proteins
      were all found to behave as wild-type. Double GRIF-1/KIF5C transfectants revealed
      co-localization. The GRIF-1/KIF5C and GRIF-1/KIF5C NMD double transfectants
      showed different subcellular distributions compared with single GRIF-1, KIF5C or
      KIF5C NMD transfections. These studies confirm the association between GRIF-1 and
      kinesin-1 NMDs. Fluorescence resonance energy transfer studies are ongoing to
      characterize this interaction in more detail.

PMID- 16417481
TI  - Increased expression of glial fibrillary acidic protein fragments and mu-calpain
      activation within the hippocampus of prion-infected mice.
AB  - Prion diseases are characteristically accompanied by marked astrocytic
      activation, which is initiated relatively early in the disease process. Using the
      intracerebrally injected ME7 strain of prion agent to model disease, we
      identified an expected increase in GFAP (glial fibrillary acidic protein) but
      additionally noted an accumulation of GFAP cleavage fragments in hippocampal
      homogenates. A time-dependent increase in hippocampal mu-calpain immunoreactivity
      within astrocytes suggests that its proteolytic activity may account for the
      cleavage of GFAP that is observed in the ME7 model. It may therefore contribute
      to the reactive gliosis that is characteristic of prion diseases.

PMID- 16417482
TI  - Glycine transporters: essential regulators of synaptic transmission.
AB  - Glycine is a major inhibitory neurotransmitter in the mammalian CNS (central
      nervous system). Glycinergic neurotransmission is terminated by the uptake of
      glycine into glycinergic nerve terminals and neighbouring glial cells. This
      uptake process is mediated by specific Na(+)/Cl(-)-dependent GlyTs (glycine
      transporters), GlyT1 and GlyT2. GlyT1, in addition, is thought to regulate the
      concentration of glycine at excitatory synapses containing NMDARs (N-methyl-D
      aspartate receptors), which require glycine as a co-agonist. We have analysed the
      physiological roles and regulation of GlyT1 and GlyT2 by generating transporter
      deficient mice and searching for interacting proteins. Our genetic results
      indicate that at glycinergic synapses, the glial transporter GlyT1 catalyses the
      removal of glycine from the synaptic cleft, whereas GlyT2 is required for the re
      uptake of glycine into nerve terminals, thereby allowing for neurotransmitter
      reloading of synaptic vesicles. Both GlyT1 and GlyT2 are essential for CNS
      function, as revealed by the lethal phenotypes of the respective knockout mice.
      Mice expressing only a single GlyT1 allele are phenotypically normal but may have
      enhanced NMDAR function. GlyT2 is highly enriched at glycinergic nerve terminals,
      and Ca(2+)-triggered exocytosis and internalization are thought to regulate GlyT2
      numbers in the pre-synaptic plasma membrane. We have identified different
      interacting proteins that may play a role in GlyT2 trafficking and/or pre
      synaptic localization.

PMID- 16417483
TI  - The synapse proteome and phosphoproteome: a new paradigm for synapse biology.
AB  - Synapse proteomics has recently resulted in a quantum leap in knowledge of the
      protein composition of brain synapses and its phosphorylation. We now have the
      first draft picture of the synapse, comprising approximately 1000 proteins. This
      is not matched by available methods of functional analysis either in reduced
      systems or in whole animals. Fewer than 20% of synapse proteome proteins have a
      known function in the nervous system. A concerted effort is required to establish
      new technical approaches before we can understand the diversity of functions
      conferred by the synapse proteome on the synapse, the neuron and the animal. This
      review will highlight this change in knowledge and discuss current technical and
      interpretative limitations challenged by synapse proteomics.

PMID- 16417484
TI  - Building a synapse: genetic analysis of glutamatergic neurotransmission.
AB  - Ionotropic glutamate receptors (iGluRs) are a critical component of the
      vertebrate central nervous system and mediate the majority of rapid excitatory
      neurotransmission. However, iGluRs are not self-regulating molecules and require
      additional proteins in order to function properly. Understanding the molecular
      architecture of functional glutamatergic synapses is therefore an important
      challenge in neurobiology. To address this question, we combine the techniques of
      genetics, molecular biology and electrophysiology in the nematode Caenorhabditis
      elegans. To date, genetic analysis has identified a number of genes required to
      build a glutamatergic synapse, including the CUB-domain transmembrane protein,
      SOL-1, which is thought to act as an auxiliary subunit that directly modifies
      iGluR function. Identifying and characterizing new proteins, such as SOL-1, in
      the relatively simple nervous system of the worm can contribute to our
      understanding of how more complex vertebrate nervous systems function.

PMID- 16417486
TI  - WAVE signalling: from biochemistry to biology.
AB  - The small GTPases Rho, Rac and Cdc42 (cell-division cycle 42) function as
      molecular switches to modulate the actin cytoskeleton. They achieve this by
      modulating the activity of downstream cellular targets. One group of Rho GTPase
      effectors, WAVE (Wiskott-Aldrich syndrome protein verprolin homologous)-1, WAVE-2
      and WAVE-3, function as scaffolds for actin-based signalling complexes. The
      present review highlights current knowledge regarding the biochemistry of the
      WAVE signalling complexes and their biological significance.

PMID- 16417485
TI  - Clathrin and synaptic vesicle endocytosis: studies at the squid giant synapse.
AB  - The role of clathrin-mediated endocytosis in SV (synaptic vesicle) recycling has
      been studied by combining molecular biology, physiology and electron microscopy
      at the squid giant synapse. Procedures that prevent clathrin from assembling into
      membrane coats, such as impairment of binding of the AP180 and AP-2 adaptor
      proteins, completely prevent membrane budding during endocytosis. These
      procedures also reduce exocytosis, presumably an indirect effect of a reduction
      in the number of SVs following block of endocytosis. Disrupting the binding of
      auxilin to Hsc70 (heat-shock cognate 70) prevents clathrin-coated vesicles from
      uncoating and also disrupts SV recycling. Taken together, these results indicate
      that a clathrin-dependent pathway is the primary means of SV recycling at this
      synapse under physiological conditions.

PMID- 16417487
TI  - Polyunsaturated fatty acids and neurotransmission in Caenorhabditis elegans.
AB  - Changes in PUFA (polyunsaturated fatty acid) metabolism can cause mental
      retardation and cognitive impairment. However, it is still unclear why altered
      levels of PUFAs result in neuronal dysfunction. Recent studies on the nematode
      Caenorhabditis elegans suggest that PUFA depletion may cause cognitive impairment
      by compromising communication among neurons. Pharmacological and
      electrophysiological experiments showed that animals devoid of most PUFAs release
      abnormally low levels of neurotransmitters. In addition, ultrastructural analysis
      revealed that synapses in these mutants are severely depleted of synaptic
      vesicles. The conclusion of these studies is that PUFAs are required to maintain
      a normal pool of synaptic vesicles at pre-synaptic sites, thus ensuring efficient
      neurotransmission.

PMID- 16417488
TI  - Temperature-sensitive paralytic mutants: insights into the synaptic vesicle
      cycle.
AB  - Forward genetic screens have identified numerous proteins with critical roles in
      neurotransmission. One particularly fruitful screening target in Drosophila has
      been TS (temperature-sensitive) paralytic mutants, which have revealed proteins
      acutely required in neuronal signalling. In the present paper, we review recent
      insights and current questions from one recently cloned TS paralytic mutant, rbo
      (rolling blackout). The rbo mutant identifies a putative integral lipase of the
      pre-synaptic plasma membrane that is required for the SV (synaptic vesicle)
      cycle. Identification of this mutant adds to a growing body of evidence that
      lipid-modifying enzymes locally control specialized lipid microenvironments and
      lipid signalling pathways with key functions regulating neurotransmission
      strength. The RBO protein is absolutely required for phospholipase C signalling
      in phototransduction. We posit that RBO might be required to regulate the
      availability of fusogenic lipids such as phosphatidylinositol 4,5-bisphosphate
      and diacylglycerol that may directly modify membrane properties and/or activate
      lipid-binding fusogenic proteins mediating SV exocytosis.

PMID- 16417489
TI  - Overexpression of tau results in defective synaptic transmission in Drosophila
      neuromuscular junctions.
AB  - Synaptic dysfunction is believed to be an early pathological change in
      neurodegenerative diseases and may cause the earliest clinical symptoms. We have
      used Drosophila to model a tauopathy in order to analyse the earliest neuronal
      and synaptic dysfunction. Our work has shown that overexpression of human tau
      (0N3R) in larval motor neurons causes a disruption of axonal transport and a
      morphological and functional disruption of NMJs (neuromuscular junctions). Tau
      expressing NMJs are smaller with an abnormal structure. Despite abnormal
      morphology, tau-expressing NMJs retain synaptotagmin expression and can form
      active zones. Tau-expressing NMJs are functionally abnormal and exhibit disrupted
      vesicle cycling and synaptic transmission. At low-frequency stimulation (1 Hz),
      ESPs (evoked synaptic potentials) produced by tau-expressing motor neurons were
      indistinguishable from wild-type; however, following high-frequency stimulation
      (50 Hz), ESPs from tau-expressing NMJs were significantly decreased in amplitude.
      To investigate the mechanism underlying the change in ESPs, we analysed the
      relative numbers and distribution of mitochondria. This revealed that motor
      neurons expressing tau had a significant reduction in the number of detectable
      mitochondria in the pre-synaptic terminal. Our results demonstrate that tau
      overexpression results in synaptic dysfunction, associated with a reduced
      complement of functional mitochondria. These findings suggest that disruption of
      axonal transport and synaptic transmission may be key components of the
      pathogenic mechanism that underlie neuronal dysfunction in the early stages of
      tauopathies.

PMID- 16417490
TI  - The Escherichia coli cytochrome c maturation (Ccm) apparatus can mature
      cytochromes with an extra cysteine within or adjacent to the CXXCH motif.
AB  - c-Type cytochromes are characterized by covalent attachment of haem to protein
      through thioether bonds between the vinyl groups of the haem and the thiols of a
      Cys-Xaa-Xaa-Cys-His motif. Proteins of this type play crucial roles in the
      biochemistry of the nitrogen cycle. Many Gram-negative bacteria use the Ccm
      (cytochrome c maturation) proteins for the post-translational haem attachment to
      their c-type cytochromes. The Ccm system can correctly mature c-type cytochromes
      with CCXXCH, CCXCH, CXCCH and CXXCHC motifs, even though these are not found
      naturally and the extra cysteine might, in principle, disrupt the biogenesis
      proteins. The non-occurrence of these motifs probably relates to the destructive
      chemistry that can occur if a free thiol reacts with haem iron to generate a
      radical.

PMID- 16417491
TI  - Specificity of FNR-type regulators in Paracoccus denitrificans.
AB  - The three FNR (fumarate and nitrate reductase regulatory protein)-type
      transcription activators of Paracoccus denitrificans, NarR, NnrR and FnrP, appear
      to have specific tasks in gene regulation during the switch from aerobic growth
      to denitrification. We here set out a series of experiments to get a fundamental
      understanding of the mechanism underlying this specificity. In one of these, we
      changed the nucleotide sequence of an NnrR box, the binding site for NnrR, into
      one found in FnrP-regulated promoters. As a result, we observed a change in
      regulation of that promoter from NnrR to FnrP. In a second series, we constructed
      hybrid promoters of NnrR-, NarR- and FnrP-regulated promoters and analysed their
      expression profiles in cells grown under various growth conditions. Our results
      indicate that the specificity of the FNR-type regulators is determined in part by
      the quality of the FNR box and in part by the sequences downstream of the FNR
      box. The latter suggests that specific sigma factors are involved in binding any
      of the Fnr-type regulators in P. denitrificans.

PMID- 16417493
TI  - Use of functional genes to quantify denitrifiers in the environment.
AB  - During the last decade, application of molecular methods using cultivation
      independent approaches has provided new insights into the composition and
      structure of denitrifying communities in various environments. However, little is
      known about their abundance, and quantification is still performed using
      cultivation-based approaches, which are not only biased by the inability to
      cultivate of many micro-organisms but also fastidious and time-consuming. Two
      types of cultivation-independent approaches have recently been developed to
      quantify denitrifiers. The first type, which is based on the hybridization
      technique, comprises the use of Southern hybridization and DNA arrays. The second
      type, based on PCR, comprises the use of MPN (most probable number)-PCR,
      competitive PCR or real-time PCR. In this review, these different approaches will
      be presented with examples of their application in environmental studies.

PMID- 16417492
TI  - Biochemical and regulatory properties of a respiratory island encoded by a
      conjugative plasmid in the extreme thermophile Thermus thermophilus.
AB  - In the present paper, we summarize the current knowledge on the first step of the
      denitrification pathway in the ancestral extreme thermophilic bacterium Thermus
      thermophilus. In this organism, nitrate respiration is performed by a mobilizable
      respiratory island that encodes a new type of respiratory NADH dehydrogenase as
      electron donor, a tetrameric membrane nitrate reductase as final electron
      acceptor, two nitrate/nitrite transporters and the transcription factors required
      for their expression in response to nitrate and anoxia.

PMID- 16417494
TI  - Microarray analysis of gene regulation by oxygen, nitrate, nitrite, FNR, NarL and
      NarP during anaerobic growth of Escherichia coli: new insights into microbial
      physiology.
AB  - RNA was isolated from cultures of Escherichia coli strain MG1655 and derivatives
      defective in fnr, narXL, or narXL with narP, during aerobic growth, or anaerobic
      growth in the presence or absence of nitrate or nitrite, in non-repressing media
      in which both strain MG1655 and an fnr deletion mutant grew at similar rates.
      Glycerol was used as the non-repressing carbon source and both trimethylamine-N
      oxide and fumarate were added as terminal electron acceptors. Microarray data
      supplemented with bioinformatic data revealed that the FNR (fumarate and nitrate
      reductase regulator) regulon includes at least 104, and possibly as many as 115,
      operons, 68 of which are activated and 36 are repressed during anaerobic growth.
      A total of 51 operons were directly or indirectly activated by NarL in response
      to nitrate; a further 41 operons were repressed. Four subgroups of genes
      implicated in management of reactive nitrogen compounds, NO and products of NO
      metabolism, were identified; they included proteins of previously unknown
      function. Global repression by the nitrate- and nitrite-responsive two-component
      system, NarQ-NarP, was shown for the first time. In contrast with the frdABCD,
      aspA and ansB operons that are repressed only by NarL, the dcuB-fumB operon was
      among 37 operons that are repressed by NarP.

PMID- 16417495
TI  - The Bradyrhizobium japonicum napEDABC genes are controlled by the FixLJ-FixK(2)
      NnrR regulatory cascade.
AB  - Nitrate respiration by the N(2)-fixing symbiotic bacteria Bradyrhizobium
      japonicum USDA110 is mediated by a Nap (periplasmic nitrate reductase) encoded by
      the napEDABC genes. Expression of a transcriptional fusion of the nap promoter
      region to the reporter gene lacZ, P(napE)-lacZ, was very low in aerobically grown
      cells of USDA110, but expression was induced approx. 3-fold when the cells were
      cultured under microaerobic conditions, and 12-fold when nitrate was added to the
      microaerobic incubation medium. The P(napE)-lacZ fusion was not expressed in the
      fixL 7403, fixJ 7360 and fixK(2) 9043 mutant strains. Microaerobic induction of
      the P(napE)-lacZ fusion was retained in the nnrR 8678 mutant, but no increase in
      beta-galactosidase activity was observed upon nitrate addition. Western-blot and
      Methyl Viologen-dependent nitrate reductase activity assays showed that synthesis
      and activity of the catalytic NapA subunit in USDA110 was similar to that in the
      napC 0906 and nirK GRK308 mutant strains incubated microaerobically with nitrate.
      These results suggest that nitrate and nitrite, which are not reduced by the napC
      0906 and nirK GRK308 mutant cells respectively, induced the synthesis and
      activity of NapA; conversely, formation of endogenous NO was not required for
      induction of Nap expression.

PMID- 16417496
TI  - Different responses to nitrate and nitrite by the model organism Escherichia coli
      and the human pathogen Neisseria gonorrhoeae.
AB  - The ability of Escherichia coli to use both nitrate and nitrite as terminal
      electron acceptors during anaerobic growth is mediated by the dual-acting two
      component regulatory systems NarX-NarL and NarQ-NarP. In contrast, Neisseria
      gonorrhoeae responds only to nitrite: it expresses only NarQ-NarP. We have shown
      that although N. gonorrhoeae NarQ can phosphorylate E. coli NarL and NarP, the N.
      gonorrhoeae NarP is unable to regulate gene expression in E. coli. Mutagenesis
      experiments have revealed residues in E. coli NarQ that are essential for nitrate
      and nitrite sensing. Chimaeric proteins revealed domains of NarQ that are
      important for ligand sensing.

PMID- 16417497
TI  - Respiratory nitrate and nitrite pathway in the denitrifier haloarchaeon Haloferax
      mediterranei.
AB  - Haloferax mediterranei cells are able to use high nitrate or nitrite
      concentrations as electron acceptors under anoxic conditions. The nar operon,
      which has eight open reading frames, has been sequenced and its regulation has
      been characterized at the transcriptional level. The narG and narH genes encode
      the Nar (respiratory nitrate reductase) catalytic subunit (NarG) and the electron
      transfer Nar subunit (NarH) respectively. Nar has been purified and characterized
      in vitro. This characterization has included protein-film voltammetry and
      preliminary EPR studies.

PMID- 16417498
TI  - Developing structure-based models to predict substrate specificity of D-group
      (Type II) molybdenum enzymes: application to a molybdo-enzyme of unknown function
      from Archaeoglobus fulgidus.
AB  - The AF0174-AF0176 gene cluster in Archaeoglobus fulgidus encodes a putative
      oxyanion reductase of the D-type (Type II) family of molybdo-enzymes. Sequence
      analysis reveals that the catalytic subunit AF0176 shares low identity (31-32%)
      and similarity (41-42%) to both NarG and SerA, the catalytic components of the
      respiratory nitrate and selenate reductases respectively. Consequently,
      predicting the oxyanion substrate selectivity of AF0176 has proved difficult
      based solely on sequence alignments. In the present study, we have modelled both
      AF0176 and SerA on the recently determined X-ray structure of the NAR (nitrate
      reductase) from Escherichia coli and have identified a number of key amino acid
      residues, conserved in all known NAR sequences, including AF0176, that we
      speculate may enhance selectivity towards trigonal planar (NO(3)(-)) rather than
      tetrahedral (SeO(4)(2-) and ClO(4)(-)) substrates.

PMID- 16417499
TI  - Evolution of the soluble nitrate reductase: defining the monomeric periplasmic
      nitrate reductase subgroup.
AB  - Bacterial nitrate reductases can be classified into at least three groups
      according to their localization and function, namely membrane-bound (NAR) or
      periplasmic (NAP) respiratory and cytoplasmic assimilatory (NAS) enzymes.
      Monomeric NASs are the simplest of the soluble nitrate reductases, although
      heterodimeric NASs exist, and a common structural arrangement of NAP is that of a
      NapAB heterodimer. Using bioinformatic analysis of published genomes, we have
      identified more representatives of a monomeric class of NAP, which is the
      evolutionary link between the monomeric NASs and the heterodimeric NAPs. This has
      further established the monomeric structural clade of NAP. The operons of the
      monomeric NAP do not contain NapB and suggest that other redox partners are
      employed by these enzymes, including NapM or NapG predicted proteins. A
      structural alignment and comparison of the monomeric and heterodimeric NAPs
      suggests that a difference in surface polarity is related to the interaction of
      the respective catalytic subunit and redox partner.

PMID- 16417500
TI  - The assimilatory nitrate reduction system of the phototrophic bacterium
      Rhodobacter capsulatus E1F1.
AB  - The phototrophic bacterium Rhodobacter capsulatus E1F1 assimilates nitrate under
      anaerobic phototrophic growth conditions. A 17 kb DNA region encoding the nitrate
      assimilation (nas) system of this bacterium has been cloned and sequenced. This
      region includes the genes coding for a putative ABC (ATP-binding cassette)-type
      nitrate transporter (nasFED) and the structural genes for the enzymes nitrate
      reductase (nasA), nitrite reductase (nasB) and hydroxylamine reductase (hcp).
      Three genes code for putative regulatory proteins: a nitrite-sensitive repressor
      (nsrR), a transcription antiterminator (nasT) and a nitrate sensor (nasS). Other
      genes probably involved in nitrate assimilation are also present in this region.
      The sequence analysis of these genes and the biochemical properties of the
      purified nitrate, nitrite and hydroxylamine reductases are reviewed.

PMID- 16417501
TI  - Investigation into the role of the truncated denitrification chain in Rhizobium
      sullae strain HCNT1.
AB  - Most denitrifying bacteria reduce nitrate to the inert gases nitrous oxide or
      nitrogen. A remarkable exception to this is Rhizobium sullae strain HCNT1, which
      catalyses only a single step in the denitrification pathway, the reduction of
      nitrite to the reactive molecule nitric oxide. Further study demonstrated that
      HCNT1 does not encode the genes for NO reductase. Prolonged incubation of HCNT1
      under anoxic conditions revealed that the cells had reduced culturability but not
      viability when nitrite was present. This may indicate an adaptation to anoxic
      conditions to provide resistance to environmental stresses. A closely related
      strain of R. sullae, strain CC1335, which is unable to denitrify, was found to
      lose culturability but not viability irrespective of the presence of nitrite.
      When the gene for nitrite reductase was mobilized into CC1335, this increased
      culturability with or without nitrite. These results indicate that the presence
      of nitrite reductase can influence the long-term survival of R. sullae strains
      and may provide an explanation as to why HCNT1 possesses this unusual truncation
      of its denitrification electron transport chain.

PMID- 16417502
TI  - Inhibiting Escherichia coli cytochrome c nitrite reductase: voltammetry reveals
      an enzyme equipped for action despite the chemical challenges it may face in
      vivo.
AB  - Escherichia coli cytochrome c nitrite reductase is one of a large family of
      homologous enzymes that are particularly prevalent in pathogenic enterobacteria.
      The enzymes are periplasmic and in vivo may find themselves challenged by
      molecules that could enhance or compromise their performance. In the present
      study, we describe protein film voltammetry in which the activity of E. coli
      cytochrome c nitrite reductase is challenged by the presence of a number of small
      molecules. These results are discussed in light of the environment(s) that the
      enzyme may face before and after colonization of a human host.

PMID- 16417503
TI  - Low-temperature kinetic measurements of microsecond freeze-hyperquench (MHQ)
      cytochrome oxidase monitored by UV-visible spectroscopy with a newly designed
      cuvette.
AB  - A special cuvette was designed to measure optical changes of MHQ (microsecond
      freeze-hyperquench) powder samples at temperatures below approx. 250 K. Reduced
      cytochrome c oxidase from Paracoccus denitrificans was reacted with O(2) for 100
      micros, frozen as a powder and transferred to the cuvette. Subsequently,
      cytochrome oxidase was allowed to react further following stepwise increments of
      the temperature from 100 K up to 250 K while recording spectra between 300 and
      700 nm. The temperature was raised only when no further changes in the spectra
      could be detected. The experiment yielded spectra of the A, P(M), F and O
      intermediate states. This demonstrated that the catalytic cycle of cytochrome
      oxidase at low temperature is similar to that at room temperature and so verifies
      the suitability of this method for the study of enzymes with high catalytic
      centre activity.

PMID- 16417504
TI  - Organization of the respiratory chain of Neisseria meningitidis.
AB  - The ability of Neisseria meningitidis to utilize both oxygen and nitrogen oxides
      as respiratory substrates allows it to thrive in the diverse environment of the
      human host. Genome analysis highlighted genes encoding a cbb(3) cytochrome
      oxidase, the aniA nitrite reductase gene and the norB nitric oxide reductase
      gene. In the present study, we used myxothiazol as an inhibitor of the bc(1)
      complex in intact cells and demonstrated that electron flow to nitrite reductase
      and the cytochrome oxidase, but not NO reductase, passes via the cytochrome bc(1)
      complex. UV-visible spectrophotometry of intact cells demonstrated that oxygen
      oxidizes c-type and b-type cytochromes. Oxidation of cytochromes by nitrite was
      only seen in microaerobically precultured whole cells, and the predominant
      oxidizable cytochromes were b-type. These are likely to be associated with the
      oxidation of a b-haem-containing nitric oxide reductase. Nitrite inhibits the
      oxidation of cytochromes by oxygen in a nitrite reductase-independent manner,
      indicating that nitrite may inhibit oxidase activity directly, as well as via the
      intermediate of denitrification, nitric oxide.

PMID- 16417505
TI  - Comparison of the structural and kinetic properties of the cytochrome c nitrite
      reductases from Escherichia coli, Wolinella succinogenes, Sulfurospirillum
      deleyianum and Desulfovibrio desulfuricans.
AB  - The recent crystallographic characterization of NrfAs from Sulfurospirillum
      deleyianum, Wolinella succinogenes, Escherichia coli and Desulfovibrio
      desulfuricans allows structurally conserved regions to be identified. Comparison
      of nitrite and sulphite reductase activities from different bacteria shows that
      the relative activities vary according to organism. By comparison of both amino
      acid sequences and structures, differences can be identified in the monomer
      monomer interface and the active-site channel; these differences could be
      responsible for the observed variance in substrate activity and indicate that
      subtle changes in the NrfA structure may optimize the enzyme for different roles.

PMID- 16417507
TI  - What is the substrate specificity of the System I cytochrome c biogenesis
      apparatus?
AB  - c-Type cytochromes are characterized by covalent attachment of haem to protein
      through thioether bonds between the vinyl groups of the haem and the thiols of a
      CXXCH motif. Proteins of this type play crucial roles in the biochemistry of the
      nitrogen cycle. Many Gram-negative bacteria use the Ccm (cytochrome c maturation)
      proteins for the post-translational haem attachment to their c-type cytochromes;
      in the present paper, we discuss the substrate specificity of the Ccm apparatus.
      The main conclusion is that the feature recognized and required in the
      apocytochrome is simply the two cysteines and the histidine of the haem-binding
      motif.

PMID- 16417506
TI  - Multiple haem lyase genes indicate substrate specificity in cytochrome c
      biogenesis.
AB  - c-Type cytochromes are a widespread class of proteins that play a vital role in
      the energy-conserving metabolism of prokaryotic and eukaryotic organisms. The key
      event in cytochrome c biogenesis is the covalent attachment of the haem cofactor
      to two (or rarely one) cysteine residues arranged in a haem c-binding motif such
      as CX(2-4)CH, CXXCK or X(3)CH. This reaction is catalysed by the membrane-bound
      enzyme CCHL (cytochrome c haem lyase). Different CCHLs have been described and
      some of them are dedicated to distinct haem c-binding motifs of cytochromes that
      are encoded in the vicinity of the respective CCHL gene. Various bacterial
      genomes contain multiple copies of CCHL-encoding genes, suggesting the presence
      of non-conventional or even as yet unrecognized haem c-binding motifs. This
      assumption is exemplified in the present study using the proteobacterium
      Wolinella succinogenes as a model organism whose genome encodes three CCHL
      isoenzymes. The discovery of a novel conserved multihaem cytochrome c (MccA) is
      described.

PMID- 16417508
TI  - Cyanide metabolism of Pseudomonas pseudoalcaligenes CECT5344: role of
      siderophores.
AB  - Cyanide is one of the most potent and toxic chemicals produced by industry. The
      jewelry industry of Cordoba (Spain) generates a wastewater (residue) that
      contains free cyanide, as well as large amounts of cyano-metal complexes. Cyanide
      is highly toxic to living systems because it forms very stable complexes with
      transition metals that are essential for protein function. In spite of its
      extreme toxicity, some organisms have acquired mechanisms to avoid cyanide
      poisoning. The biological assimilation of cyanide needs the concurrence of three
      separate processes: (i) a cyanide-insensitive respiratory chain, (ii) a system
      for iron acquisition (siderophores) and (iii) a cyanide assimilation pathway.
      Siderophores are low-molecular-mass compounds (600-1500 Da) that scavenge iron
      (Fe(3+)) ions (usually with extremely high affinity) from the environment under
      iron-limiting conditions. There are two main classes of siderophores: catechol
      and hydroxamate types. The catechol-type siderophores chelate ferric ion via a
      hydroxy group, whereas the hydroxamate-type siderophores bind iron via a carbonyl
      group with the adjacent nitrogen. In the presence of cyanide, bacterial
      proliferation requires this specific metal uptake system because siderophores are
      able to break down cyano-metal complexes. Pseudomonas pseudoalcaligenes CECT5344
      is able to use free cyanide or cyano-metal complexes as nitrogen source. A
      proteomic approach was used for the isolation and identification, in this strain,
      of a protein that was induced in the presence of cyanide, namely CN0, that is
      involved in siderophore biosynthesis in response to cyanide. An overview of
      bacterial cyanide degradation pathways and the involvement of siderophores in
      this process are presented.

PMID- 16417509
TI  - A multitude of CRP/FNR-like transcription proteins in Bradyrhizobium japonicum.
AB  - In Bradyrhizobium japonicum, the nitrogen-fixing soya bean endosymbiont and
      facultative denitrifier, three CRP (cAMP receptor protein)/FNR (fumarate and
      nitrate reductase regulatory protein)-type transcription factors [FixK(1),
      FixK(2) and NnrR (nitrite and nitric oxide reductase regulator)] have been
      studied previously in the context of the regulation of nitrogen fixation and
      denitrification. The gene expression of both fixK(1) and nnrR depends on FixK(2),
      which acts as a key distributor of the 'low-oxygen' signal perceived by the two
      component regulatory system FixLJ. While the targets for FixK(1) are not known,
      NnrR transduces the nitrogen oxide signal to the level of denitrification gene
      expression. Besides these three regulators, the complete genome sequence of this
      organism has revealed the existence of 13 additional CRP/FNR-type proteins whose
      functions have not yet been studied. Based on sequence similarity and
      phylogenetic analysis, we discuss in this paper the peculiarities of these
      additional factors.

PMID- 16417510
TI  - Metabolic regulation of nitrogen fixation in Rhodospirillum rubrum.
AB  - Nitrogenase activity in Rhodospirillum rubrum is post-translationally regulated
      by DRAG (dinitrogenase reductase glycohydrolase) and DRAT (dinitrogenase
      reductase ADP-ribosylation transferase). When a sudden increase in fixed nitrogen
      concentration or energy depletion is sensed by the cells, DRAG is inactivated and
      DRAT activated. We propose that the regulation of DRAG is dependent on its
      location in the cell and the presence of an ammonium-sensing protein.

PMID- 16417511
TI  - Role of the central region of NifL in conformational switches that regulate
      nitrogen fixation.
AB  - The NifL regulatory protein is an anti-activator that tightly regulates
      transcription of genes required for nitrogen fixation in Azotobacter vinelandii
      by controlling the activity of its partner protein NifA through the formation of
      a protein-protein complex. NifL modulates the activity of NifA in response to the
      redox, carbon and nitrogen status to ensure that nitrogen fixation occurs only
      under physiological conditions that are appropriate for nitrogenase activity. The
      domain architecture of NifL is similar to that of some histidine protein kinases,
      with two N-terminal PAS (PER, ARNT, SIM) domains, one of which contains an FAD
      cofactor that senses the redox status, and a C-terminal domain containing
      conserved residues that constitutes the nucleotide-binding domain of the GHKL
      (gyrase, Hsp90, histidine kinase, MutL) superfamily of ATPases. We have evidence
      that the central region of NifL, which is located between the PAS domains and the
      C-terminal GHKL nucleotide-binding domain, plays a crucial role in the
      propagation of signals perceived in response to the redox and fixed nitrogen
      status and that this region participates in conformational changes that switch
      NifL between active and inactive states. We have identified a critical arginine
      residue in the central region of NifL that participates in the conformational
      switch that activates NifL. Mutations in the central region of NifL that disable
      the redox-sensing function of NifL but leave the protein competent to respond to
      the nitrogen signal conveyed by the signal transduction protein GlnK have also
      been isolated. Our results suggest that the topological relationship between the
      central region and the GHKL domain may alter as a consequence of conformational
      changes induced in response to signal perception.

PMID- 16417512
TI  - Analysis of community composition of biofilms in a submerged filter system for
      the removal of ammonia and phenol from industrial wastewater.
AB  - The bacterial diversity of a submerged filter, used for the removal of ammonia
      and phenol from an industrial wastewater with high salinity, was studied by a
      cultivation-independent approach based on PCR/TGGE (temperature-gradient gel
      electrophoresis). The wastewater treatment plant (laboratory scale) combined the
      nitrification and denitrification processes and consisted of two separated
      columns (one anoxic and one aerated) connected through a valve. The spatial
      diversity of bacterial communities in the plant biofilms was analysed by taking
      samples at four different heights in the system. TGGE profiles of PCR-amplified
      sequences of the 16 S rRNA gene (V3-hypervariable region) showed significant
      variations of the bacterial diversity, mainly depending on the concentration of
      O(2) along the system. Several bands separated by TGGE were reamplified and
      sequenced, in order to explore the composition of the microbial communities in
      the biofilms. Most of the sequenced bands (10 out of 13) were closely related to
      the 16 S rRNA gene of marine alpha-proteobacteria, mainly grouping in the
      periphery of the genus Roseobacter. Other sequences were related to those of
      gamma-proteobacteria, the nitrite oxidizer Nitrospira marina and anaerobic phenol
      degrading bacteria of the Desulfobacteraceae.

PMID- 16417513
TI  - Approaches to assess the biodiversity of bacteria in natural habitats.
AB  - Any attempt to characterize a bacterial community and their functional genes
      coding for enzymes of the nitrogen cycle is faced with its extreme biodiversity.
      Novel techniques, based on PCR amplification of target genes in DNA from
      environmental samples, have been developed for characterizing both cultured and
      as yet uncultured bacteria in the last few years. Computer-based assignment tools
      have now been developed utilizing terminal restriction fragments obtained from
      digestions with multiple restriction enzymes. Such programs allow the gross
      characterization of bacterial life in any complex bacterial community with
      confidence.

PMID- 16417514
TI  - Global impact and application of the anaerobic ammonium-oxidizing (anammox)
      bacteria.
AB  - In the anaerobic ammonium oxidation (anammox) process, ammonia is oxidized with
      nitrite as primary electron acceptor under strictly anoxic conditions. The
      reaction is catalysed by a specialized group of planctomycete-like bacteria.
      These anammox bacteria use a complex reaction mechanism involving hydrazine as an
      intermediate. The reactions are assumed to be carried out in a unique prokaryotic
      organelle, the anammoxosome. This organelle is surrounded by ladderane lipids,
      which make the organelle nearly impermeable to hydrazine and protons. The
      localization of the major anammox protein, hydrazine oxidoreductase, was
      determined via immunogold labelling to be inside the anammoxosome. The anammox
      bacteria have been detected in many marine and freshwater ecosystems and were
      estimated to contribute up to 50% of oceanic nitrogen loss. Furthermore, the
      anammox process is currently implemented in water treatment for the low-cost
      removal of ammonia from high-strength waste streams. Recent findings suggested
      that the anammox bacteria may also use organic acids to convert nitrate and
      nitrite into dinitrogen gas when ammonia is in short supply.

PMID- 16417515
TI  - Role of nitrogen oxides in the metabolism of ammonia-oxidizing bacteria.
AB  - Ammonia-oxidizing bacteria (AOB) can use oxygen and nitrite as electron
      acceptors. Nitrite reduction by Nitrosomonas is observed under three conditions:
      (i) hydrogen-dependent denitrification, (ii) anoxic ammonia oxidation with
      nitrogen dioxide (NO(2)) and (iii) NO(x)-induced aerobic ammonia oxidation. NO(x)
      molecules play an important role in the conversion of ammonia and nitrite by AOB.
      Absence of nitric oxide (NO), which is generally detectable during ammonia
      oxidation, severely impairs ammonia oxidation by AOB. The lag phase of recovery
      of aerobic ammonia oxidation was significantly reduced by NO(2) addition.
      Acetylene inhibition tests showed that NO(2)-dependent and oxygen-dependent
      ammonia oxidation can be distinguished. Addition of NO(x) increased specific
      activity of ammonia oxidation, growth rate and denitrification capacity.
      Together, these findings resulted in a hypothetical model on the role of NO(x) in
      ammonia oxidation: the NO(x) cycle.

PMID- 16417516
TI  - NO-dependent transcriptional activation of gene expression in Ralstonia eutropha
      H16.
AB  - The sigma54-dependent transcriptional regulator NorR of Ralstonia eutropha H16
      activates gene expression in response to nitric oxide (NO). The N-terminal domain
      of NorR is thought to be involved in signal perception. A C112S exchange within
      this domain abolished promoter activation by the mutated protein, indicating that
      Cys(112) is essential for the signalling mechanism of NorR. The DNA region
      recognized by NorR contains three copies of a conserved element termed the NorR
      box. Alteration of bases within any of the NorR-boxes resulted in a significant
      decrease in promoter activation. Therefore all three boxes have to be recognized
      by NorR to activate its target promoter. NorR controls expression of an operon
      that encodes a redox-active non-haem-iron protein NorA and an NO reductase NorB.
      NorA exerts a negative effect on signal-dependent promoter activation by NorR.
      Optical spectroscopy of purified NorA indicates that the reduced protein can
      react with NO to form a ferrous nitrosyl adduct. Hence, NO binding by NorA opens
      up the possibility that NorA and NorR compete for NO in the cytoplasm.

PMID- 16417517
TI  - N-oxide sensing and denitrification: the DNR transcription factors.
AB  - All denitrifiers can keep the steady-state concentrations of nitrite and nitric
      oxide (NO) below cytotoxic levels by controlling the expression of
      denitrification gene clusters by redox signalling through transcriptional
      regulators belonging to the CRP (cAMP receptor protein)/FNR (fumarate and nitrate
      reductase regulator) superfamily.

PMID- 16417518
TI  - Proton transfer in bacterial nitric oxide reductase.
AB  - The NOR (nitric oxide reductase) from Paracoccus denitrificans catalyses the two
      electron reduction of NO to N(2)O (2NO+2H(+)+2e(-)-->N(2)O+H(2)O). The NOR is a
      divergent member of the superfamily of haem-copper oxidases, oxygen-reducing
      enzymes which couple the reduction of oxygen with translocation of protons across
      the membrane. In contrast, reduction of NO catalysed by NOR is non-electrogenic
      which, since electrons are supplied from the periplasmic side of the membrane,
      implies that the protons needed for NO reduction are also taken from the
      periplasm. Thus NOR must contain a proton-transfer pathway leading from the
      periplasmic side of the membrane into the catalytic site. The proton pathway has
      not been identified, and the mechanism and timing of proton transfer during NO
      reduction is unknown. To address these questions, we have studied the reaction
      between NOR and the chemically less reactive oxidant O(2). When fully reduced NOR
      reacts with O(2), proton-coupled electron transfer occurs in a reaction that is
      rate-limited by internal proton transfer from a group with a pK(a) of 6.6. This
      group is presumably an amino acid residue close to the active site that acts as a
      proton donor also during NO reduction. The results are discussed in the framework
      of a structural model that identifies possible candidates for the proton donor as
      well as for the proton-transfer pathway.

PMID- 16417519
TI  - Mechanism of transcriptional regulation by the Escherichia coli nitric oxide
      sensor NorR.
AB  - Nitric oxide (NO) is a highly reactive water-soluble gas encountered by bacteria
      endogenously as an intermediate of denitrification and exogenously as one of the
      radical species deployed by macrophages against invading pathogens. Bacteria
      therefore require a mechanism to detoxify NO. Escherichia coli flavorubredoxin
      and its associated oxidoreductase, encoded by the norV and norW genes
      respectively, reduces NO to nitrous oxide under anaerobic conditions.
      Transcription of the norVW genes is activated in response to NO by the sigma(54)
      dependent regulator NorR, a member of the prokaryotic enhancer binding protein
      family. NorR binds co-operatively to three enhancer sites to regulate
      transcription of both norVW and the divergently transcribed norR gene. In the
      present paper, we show that disruption of any one of the three GT-(N(7))-AC NorR
      binding sites in the norR-norVW intergenic region prevents both activation of
      norVW expression and autogenous repression of the norR promoter by NorR. We have
      recently demonstrated that the N-terminal GAF (cGMP-specific and -stimulated
      phosphodiesterases, Anabaena adenylate cyclases and Escherichia coli FhlA) domain
      of NorR contains a non-haem mononuclear iron centre and senses NO by formation of
      a mono-nitrosyl iron complex. Site-directed mutagenesis has identified candidate
      protein ligands to the ferrous iron centre in the GAF domain.

PMID- 16417520
TI  - The role of Bradyrhizobium japonicum nitric oxide reductase in nitric oxide
      detoxification in soya bean root nodules.
AB  - The identification of nitric oxide-bound leghaemoglobin within soya bean nodules
      has led to the question of how Bradyrhizobium japonicum bacteroids overcome the
      toxicity of this nitric oxide. It has previously been shown that one candidate
      for nitric oxide detoxification, the respiratory nitric oxide reductase, is
      expressed in soya bean nodules from plants supplied with nitrate. In this paper,
      the role of this enzyme in nitric oxide detoxification is assessed and discussion
      is provided on other possible B. japonicum nitric oxide detoxification systems.

PMID- 16417521
TI  - Effect of combined oxidative and nitrosative stress on Neisseria meningitidis.
AB  - Reactive oxygen and nitrogen species are produced by the human immune system in
      response to infection. Methods to detoxify these reactive species are vital to
      the survival of human pathogens, such as Neisseria meningitidis, which is the
      major aetiological agent of bacterial meningitis. Following activation,
      macrophages produce superoxide (O(2)(-)), hydrogen peroxide (H(2)O(2)) and nitric
      oxide (NO). The toxicity of O(2)(-), generated using X/Xo (xanthine/xanthine
      oxidase), and H(2)O(2) was investigated in the presence and absence of the NO
      donor DEA-NONOate [2-(N,N-diethylamino)-diazenolate-2-oxide diethylammonium
      salt]. Most of the toxicity from X/Xo was due to H(2)O(2). In N. meningitidis, NO
      decreased the toxicity of the H(2)O(2). In contrast, in the enteric bacterium
      Escherichia coli, NO increased the toxicity of the H(2)O(2).

PMID- 16417522
TI  - Nitric oxide-sensing mechanisms in Escherichia coli.
AB  - Exposure of Escherichia coli to nitric oxide (NO) or nitrosating agents causes
      significant changes in patterns of gene expression. Three recent studies have
      used microarrays to analyse the response of the E. coli transcriptome to NO and
      nitrosative stress. Drawing on the array data, I review our current understanding
      of the E. coli regulatory systems that are involved.

PMID- 16417523
TI  - The chemical chaperone CFcor-325 repairs folding defects in the transmembrane
      domains of CFTR-processing mutants.
AB  - Most patients with CF (cystic fibrosis) express a CFTR [CF TM (transmembrane)
      conductance regulator] processing mutant that is not trafficked to the cell
      surface because it is retained in the endoplasmic reticulum due to altered
      packing of the TM segments. CL4 (cytoplasmic loop 4) connecting TMs 10 and 11 is
      a 'hot-spot' for CFTR processing mutations. The chemical chaperone CFcor-325 (4
      cyclohexyloxy-2-{1-[4-(4-methoxy-benezenesulphonyl)piperazin-1-yl]-ethyl}
      quinazoline) rescued most CL4 mutants. To test if CFcor-325 promoted correct
      folding of the TMDs (TM domains), we selected two of the CL4 mutants (Q1071P and
      H1085R) for disulphide cross-linking analysis. Pairs of cysteine residues that
      were cross-linked in mature wild-type CFTR were introduced into mutants Q1071P
      and H1085R. The cross-linking patterns of the Q1071P or H1085R double cysteine
      mutants rescued with CFcor-325 were similar to those observed with mature wild
      type double cysteine proteins. These results show that CFcor-325 rescued CFTR
      mutants by repairing the folding defects in the TMDs.

PMID- 16417525
TI  - Who's afraid of status epilepticus?

PMID- 16417524
TI  - Akt phosphorylates and suppresses the transactivation of retinoic acid receptor
      alpha.
AB  - The transactivation of nuclear receptors is regulated by both ligand binding and
      phosphorylation. We previously showed that RARalpha (retinoic acid receptor
      alpha) phosphorylation by c-Jun N-terminal kinase contributes to retinoid
      resistance in a subset of NSCLC cells (non-small cell lung cancer cells), but the
      aetiology of this resistance in the remainder has not been fully elucidated
      [Srinivas, Juroske, Kalyankrishna, Cody, Price, Xu, Narayanan, Weigel and Kurie
      (2005) Mol. Cell. Biol. 25, 1054-1069]. In the present study, we report that Akt,
      which is constitutively activated in NSCLC cells, phosphorylates RARalpha and
      inhibits its transactivation. Biochemical and functional analyses showed that Akt
      interacts with RARalpha and phosphorylates the Ser96 residue of its DNA-binding
      domain. Mutation of Ser96 to alanine abrogated the suppressive effect of Akt.
      Overexpression of a dominant-negative form of Akt in an NSCLC cell line decreased
      RAR phosphorylation, increased RAR transactivation and enhanced the growth
      inhibitory effects of an RAR ligand. The findings presented here show that Akt
      inhibits RAR transactivation and contributes to retinoid resistance in a subset
      of NSCLC cells.

PMID- 16417526
TI  - Pharmacodynamic and pharmacokinetic characterization of interactions between
      levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock
      seizure model: an isobolographic analysis.
AB  - PURPOSE: Approximately 30% of patients with epilepsy do not experience
      satisfactory seizure control with antiepileptic drug (AED) monotherapy and often
      require polytherapy. The potential usefulness of AED combinations, in terms of
      efficacy and adverse effects, is therefore of major importance. The present study
      sought to identify potentially useful AED combinations with levetiracetam (LEV)
      METHODS: With isobolographic analysis, the mouse maximal electroshock (MES)
      induced seizure model was investigated with regard to the anticonvulsant effects
      of carbamazepine (CBZ), phenytoin, phenobarbital (PB), valproate, lamotrigine,
      topiramate (TPM), and oxcarbazepine (OXC), administered singly and in combination
      with LEV. Acute adverse effects were ascertained by use of the chimney test
      evaluating motor performance and the step-through passive-avoidance task
      assessing long-term memory. Brain AED concentrations were determined to ascertain
      any pharmacokinetic contribution to the observed antiseizure effect. RESULTS: LEV
      in combination with TPM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, was
      supraadditive (synergistic) in the MES test. Likewise, the combination of LEV
      with CBZ (at the fixed ratio of 16:1) and LEV with OXC (8:1 and 16:1) were
      supraadditive. In contrast, all other LEV/AED combinations displayed additivity.
      Furthermore, none of the investigated LEV/AED combinations altered motor
      performance and long-term memory. LEV brain concentrations were unaffected by
      concomitant AED administration, and LEV had no significant effect on brain
      concentrations of concomitant AEDs. CONCLUSIONS: These preclinical data would
      suggest that LEV in combination with TPM is associated with beneficial
      anticonvulsant pharmacodynamic interactions. Similar, but less profound effects
      were seen with OXC and CBZ.

PMID- 16417527
TI  - Evidence supporting a role of serotonin in modulation of sudden death induced by
      seizures in DBA/2 mice.
AB  - PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is a serious concern for
      epilepsy patients. DBA/2 mice are proposed as a SUDEP model, because these mice
      exhibit respiratory arrest (RA) after audiogenic seizures (AGSs), and RA is also
      implicated in human SUDEP. Respiratory mechanisms are modulated, in part, by
      serotonin. Therefore we evaluated the effects of serotoninergic agents on RA
      incidence in DBA/2 mice. METHODS: DBA/2 mice (75%) exhibited AGS and RA, and
      approximately 99% of animals could be resuscitated. The mice exhibiting RA were
      given a selective serotonin reuptake inhibitor, fluoxetine, 24 h after the
      initial AGS, and RA susceptibility was evaluated 30 min later. Ten percent of
      DBA/2 mice exhibited tonic hindlimb extension (TE) without RA, and a serotonin
      antagonist (cyproheptadine) was administered to these mice. RESULTS: Fluoxetine
      (15-25 mg/kg, i.p.) significantly reduced the incidence of RA in DBA/2 mice after
      AGSs, and this effect was reversible by 72 h. Only the 25-mg/kg dose reduced AGS
      severity. In mice exhibiting TE without RA, the incidence of RA was significantly
      increased 30 min after cyproheptadine (1-2 mg/kg i.p.). Most of these mice
      exhibited AGSs without RA again by 72 h. CONCLUSIONS: These findings indicate
      that fluoxetine reduced RA in DBA/2 mice at doses that did not reduce seizure
      severity. Because DBA/2 mice are a proposed model for human SUDEP, these data
      support evaluation of fluoxetine for SUDEP prevention in the patient population
      most susceptible to SUDEP. The data raise concern about the use of serotonin
      antagonists in this patient population.

PMID- 16417528
TI  - Chronic bilateral stimulation of the anterior thalamus of kainate-treated rats
      increases seizure frequency.
AB  - PURPOSE: Electrical stimulation of the anterior nucleus of the thalamus (ANT) is
      receiving increased attention as a novel means of controlling intractable
      epilepsy, and has entered human clinical trial. Animal data supporting the
      anticonvulsant benefit of ANT stimulation, however, has been obtained from acute
      chemoconvulsant models of epilepsy rather than models of chronic epilepsy with
      spontaneous seizures. It is unknown whether ANT stimulation is effective in
      models of chronic epilepsy. METHODS: Bilateral ANT stimulation was evaluated in
      rats with chronic epilepsy following acute status epilepticus (SE) produced by
      systemic kainic acid (KA) administration. The evolution of epilepsy following KA
      SE and the effects of ANT stimulation were monitored by continuous video-EEG.
      RESULTS: Following KA SE, most rats have 2-8 seizures per day, and the average
      seizure rate increases over time, doubling over the course of 14 weeks.
      Behavioral seizure severity, after the initial development of epilepsy, remains
      stable. Seizure frequency during ANT stimulation was 2.5 times the baseline
      seizure frequency. In some cases stimulation triggered seizures were observed.
      The effects of stimulation were specific to the ANT. Stimulation applied to
      electrodes placed outside the ANT did not significantly worsen seizure frequency.
      CONCLUSIONS: ANT stimulation exacerbated seizure frequency in rats with chronic
      epilepsy following kainate status epilepticus.

PMID- 16417529
TI  - Amygdala kindling in the WAG/Rij rat model of absence epilepsy.
AB  - PURPOSE: The kindling model in rats with genetic absence epilepsy is suitable for
      studying mechanisms involved in the propagation and generalization of seizure
      activity in the convulsive and nonconvulsive components of epilepsy. In the
      present study, we compared the amygdala kindling rate and afterdischarge
      characteristics of the nonepileptic Wistar control rat with a well-validated
      model of absence epilepsy, the WAG/Rij rat, and demonstrated the effect of
      amygdala kindling on spike-and-wave discharges (SWDs) in the WAG/Rij group.
      METHODS: Electrodes were stereotaxically implanted into the basolateral amygdala
      of rats for stimulation and recording and into the cortex for recording. After a
      recovery period, the animals were stimulated at their afterdischarge thresholds.
      EEG was recorded to analyze SWDs and afterdischarge durations. The seizure
      severity was evaluated by using Racine's 5-stage scale. RESULTS: All nonepileptic
      control and four of seven WAG/Rij animals reached a stage 5 seizure state,
      whereas three animals failed to reach stage 3, 4, or 5 and stayed at stage 2
      after application of 30 stimulations. Interestingly, WAG/Rij rats, resistant to
      kindling, demonstrated a significantly longer duration of SWDs on the first day
      of the experiment before kindling stimulation than did the kindled WAG/Rij
      animals. Additionally, the cumulative total duration and the number of SWDs after
      the kindling stimulation were statistically increased compared with SWDs before
      kindling stimulation. CONCLUSIONS: The results of our study demonstrate that the
      progress of amygdala kindling is changed in rats with genetic absence epilepsy,
      perhaps as a consequence of the hundreds of daily SWDs.

PMID- 16417530
TI  - Hippocampal T2 signal change during amygdala kindling epileptogenesis.
AB  - PURPOSE: The rat electrical amygdala kindling model is one of the most widely
      studied animal models of temporal lobe epilepsy (TLE); however, the processes
      underlying epileptogenesis in this model remain incompletely understood. Magnetic
      resonance imaging (MRI) is a powerful method to investigate epileptogenesis,
      allowing serial imaging of associated structural and functional changes in vivo.
      Here we report on the results of serial MRI acquisitions during epileptogenesis
      in this model. METHODS: Serial T2-weighted MR images were acquired before,
      during, and after the induction of kindling, to investigate the development and
      progression of imaging abnormalities. RESULTS: T2-weighted acquisitions
      demonstrated the development of regions of increased signal in the rostral
      ipsilateral regions of CA1 and dentate gyrus in kindled (five of seven) but not
      in control rats (p < 0.05). Quantification of the T2 signal demonstrated a
      significant increase in kindled animals when compared with controls, 2 weeks
      after kindling ceased, in the ipsilateral hippocampus and the hippocampal sub
      regions of CA1 and the dentate gyrus (p < 0.05). No significant difference was
      observed in hippocampal volumes between kindled or control animals at any of the
      times. CONCLUSIONS: The results of this study validate a method for acquiring
      serial MRI during amygdala kindling and demonstrate the induction of T2 signal
      abnormalities in focal regions of the hippocampus. These regions may be important
      sites for the neurobiologic changes that contribute to epileptogenesis in this
      model.

PMID- 16417531
TI  - Epileptiform activity induced by pharmacologic reduction of M-current in the
      developing hippocampus in vitro.
AB  - PURPOSE: Benign familial neonatal convulsions (BFNCs), an inheritable epilepsy
      that occurs in neonates but not in adults, is caused by hypofunctional mutations
      in genes codifying for the M-type K+ current. In an attempt to develop an in
      vitro model of this disease, we tested whether blocking M-current with
      linopirdine induces epileptiform activity in brain slices from animals of
      different ages. METHODS: Horizontal hippocampus-entorhinal cortex slices were
      obtained from neonatal (1-2 weeks after birth) and adult (8-9 weeks after birth)
      rats. Extracellular field recordings of the CA1 region were performed. After
      recording control conditions, linopirdine was added to the bath, and field
      activity was recorded continuously for 3 h. 4-Aminopyridine, a drug commonly used
      to induce epileptiform activity in vitro, was used as a control for our
      experimental conditions. RESULTS: Bath perfusion of linopirdine induced
      epileptiform activity only in slices from neonatal rats. Epileptiform activity
      consisted of interictal-like and ictal-like activity. In slices from adult rats,
      linopirdine induced erratic interictal-like activity. In contrast, 4
      aminopyridine was able to induce epileptiform activity in slices from both
      neonatal and adult rats. CONCLUSIONS: We demonstrated that blockade of M-current
      in vitro produces epileptiform activity with a developmental pattern similar to
      that observed in BNFCs. This could be an in vitro model that can be used to study
      the cellular mechanisms of epileptogenesis and the developmental features of
      BFNCs, as well as to develop some therapeutic strategies.

PMID- 16417532
TI  - Open-field behaviors and water-maze learning in the F substrain of Ihara
      epileptic rats.
AB  - PURPOSE: Genetically epileptic model rats, Ihara epileptic rat (IER/F substrain),
      have neuropathologic abnormalities and develop generalized convulsive seizures
      when they reach the age of approximately 5 months. Because the neuromorphologic
      abnormalities are centered in the hippocampus, we expected to observe spatial
      cognitive deficits. The present study aimed to evaluate emotionality and learning
      ability of the F substrain of IER. METHODS: To determine whether deficits are
      caused by inborn neuropathologic abnormalities or by repeated generalized
      convulsions, we tested nine 6- to 12-week-old IER/F rats that had not yet
      experienced seizures (experiment 1) and nine 7- to 9-month-old IER/F rats that
      had repeatedly experienced seizures (experiment 2) with identical tasks: an open
      field test and the Morris water-maze place and cue tasks. RESULTS: Both groups of
      IER/Fs showed behaviors that were different from those of control rats in the
      open-field test, and extensive learning impairments were seen in both the place
      task, which requires spatial cognition, and the cue task, which does not require
      spatial cognition but requires simple association learning. Their impaired
      performance of the cue task indicates that their deficiency was not limited to
      spatial cognition. CONCLUSIONS: Because young IER/F rats without seizure
      experiences also showed severe learning impairments, genetically programmed
      microdysgenesis in the hippocampus was suspected as a cause of the severe
      learning deficits of IER/Fs.

PMID- 16417533
TI  - Reduction of AEDs in postsurgical patients who attain remission.
AB  - PURPOSE: Little evidence guides practice regarding the reduction of antiepileptic
      drugs (AEDs) in individuals who achieve significant periods of remission after
      resective surgery. METHODS: In a prospective study of 396 individuals who
      underwent resective surgery for intractable seizures, the impact of reducing AEDs
      on relapse and predictors of relapse were examined. RESULTS: Of 301 study
      subjects who attained a 1-year seizure remission after surgery, 129 reduced from
      two to one or from one to no AEDs after achieving remission, and 162 did not
      reduce drugs. Ten patients who stopped all AEDs before attaining remission were
      excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in
      the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02).
      Patients who reduced drugs were more likely to have remitted immediately after
      hospital discharge (p<0.0001). After adjustment for this factor, little or no
      apparent impact of drug reduction on the rate of relapse was noted [rate ratio
      (RR), 1.1; 95% CI, 0.72-1.71; p=0.64 for reducing from two to one AED, and RR,
      0.85; 95% CI, 0.50-1.45; p=0.56 for reducing from one to no AEDs]. Within the 129
      patients who reduced AEDs, only delayed remission after hospital discharge was
      significantly associated with an increased rate of relapse (RR, 2.26; 95% CI,
      1.15- 4.48; p=0.02). Continued auras had a marginally significant association
      with relapse (RR, 2.06; p=0.07) CONCLUSIONS: Although many relapses in this
      cohort of postsurgical patients who achieved remission occurred in the context of
      reducing or completely eliminating AEDs, the risk was no higher than in those who
      continued AEDs. Randomized studies are needed to test the impact of drug
      reduction in seizure-free postsurgical patients.

PMID- 16417534
TI  - Efficacy and safety of levetiracetam (up to 2000 mg/day) in Taiwanese patients
      with refractory partial seizures: a multicenter, randomized, double-blind,
      placebo-controlled study.
AB  - PURPOSE: To assess the efficacy and safety of adjunctive levetiracetam (LEV)
      therapy in controlling partial-onset seizures refractory to other antiepileptic
      drugs (AEDs) in a multicenter study in Taiwanese adults. METHODS: Ninety-four
      patients aged 16-60 years with refractory partial seizures were randomized to
      receive LEV (n = 47) or placebo (47) for 14 weeks and composed the intention-to
      treat (ITT) population. After the first 2 weeks, LEV patients had their dosage
      increased from 500 mg twice daily to 1,000 mg twice daily. A 12-week maintenance
      phase followed, after which patients switched to long-term, open-label LEV
      therapy or entered a 4-week phase of medication discontinuation. RESULTS: All
      patients from the ITT population, except one LEV-treated patient with missing
      seizure-count data, were included in the primary efficacy analysis. The least
      square mean of logarithmically transformed weekly partial-seizure frequency was
      significantly lower in the LEV than in the placebo group (0.813 vs. 1.085; p =
      0.001). LEV reduced log-transformed weekly partial-seizure frequency by 23.8%
      (95% confidence interval, 10.4-35.2%) relative to placebo. Significantly more LEV
      than placebo patients (43.5% vs. 10.6%) experienced a response of a >or=50%
      decrease from baseline in weekly frequency of partial seizures [odds ratio, 6.5
      (95% CI, 2.2-19.3); p < 0.001]. Adverse events were reported in 34 (72.3%) of 47
      LEV-treated patients and 32 (68.1%) of 47 placebo patients. The three most common
      adverse events in the LEV and placebo groups were somnolence (40.4% and 14.9%),
      dizziness (14.9% and 8.5%), and headache (10.6% and 8.5%), respectively. Only
      four patients (three LEV-treated patients and one placebo patient) were withdrawn
      from the study because of adverse events. CONCLUSIONS: Adjunctive LEV therapy,
      <or=1,000 mg twice daily, was significantly more effective than placebo and was
      generally well tolerated in Taiwanese adults with treatment-resistant partial
      onset seizures.

PMID- 16417535
TI  - Effects of levetiracetam on nocturnal sleep and daytime vigilance in healthy
      volunteers.
AB  - PURPOSE: Individuals with epilepsy commonly report daytime sleepiness, attributed
      to sleep disruption (frequent arousals, awakenings, and stage shifts) induced by
      ictal and interictal activity or antiepileptic drugs (AEDs) or both. To study the
      effect of levetiracetam (LEV) on sleep, at full doses but without the
      interference of epilepsy, we investigated the sleep architecture and daytime
      vigilance in healthy adults after 3 weeks of treatment. METHODS: The study was of
      a double-blind crossover design with random allocation of multiple doses of two
      different treatments (randomly first LEV <or=2,000 mg/day or placebo for 3 weeks,
      washout for 4 weeks, and then the alternative treatment for another 3 weeks).
      Fourteen healthy volunteers were studied with polysomnography (PSG) and the
      Multiple Sleep Latency Test (MSLT). Epworth Sleepiness Scale (ESS) and sleep log
      also were evaluated. RESULTS: After treatment with LEV, statistically significant
      increases were observed in total sleep time, sleep efficiency, and time spent in
      non-rapid eye movement (NREM) sleep stages 2 and 4. Stage shifts and wake after
      sleep onset were significantly decreased. Sleep latency was normal at PSG and
      MSLT in all subjects and did not statistically differ between placebo and LEV. No
      changes were found in the ESS. CONCLUSIONS: Our findings show that in healthy
      volunteers, LEV consolidates sleep and does not modify vigilance, two appreciated
      qualities in epilepsy patients with sleep disturbance and daytime sleepiness.

PMID- 16417536
TI  - Periventricular nodular heterotopia: classification, epileptic history, and
      genesis of epileptic discharges.
AB  - PURPOSE: Periventricular nodular heterotopia (PNH) is among the most common
      malformations of cortical development, and affected patients are frequently
      characterized by focal drug-resistant epilepsy. Here we analyzed clinical, MRI,
      and electrophysiologic findings in 54 PNH patients to reevaluate the
      classification of PNH, relate the anatomic features to epileptic outcome, and
      ascertain the contribution of PNH nodules to the onset of epileptic discharges.
      METHODS: The patients were followed up for a prolonged period at the Epilepsy
      Center of our Institute. In all cases, we related MRI findings to clinical and
      epileptic outcome and analyzed interictal and ictal EEG abnormalities. In one
      patient, EEG and stereo-EEG (SEEG) recordings of seizures were compared. RESULTS:
      We included cases with periventricular nodules, also extending to white matter
      and cortex, provided that anatomic continuity was present between nodules and
      malformed cortex. Based on imaging and clinical data, patients were subdivided
      into five PNH groups: (a) bilateral and symmetrical; (b) bilateral single
      noduled; (c) bilateral and asymmetrical; (d) unilateral; and (e) unilateral with
      extension to neocortex. The latter three groups were characterized by worse
      epileptic outcome. No differences in outcome were found between unilateral PNH
      patients regardless the presence of cortical involvement. Interictal as well as
      ictal EEG abnormalities were always related to PNH location. CONCLUSIONS: The
      distinctive clinical features and epileptic outcomes in each group of patients
      confirm the reliability of the proposed classification. Ictal EEG and SEEG
      recordings suggest that seizures are generated by abnormal anatomic circuitries
      including the heterotopic nodules and adjacent cortical areas.

PMID- 16417537
TI  - Involvement of medial pulvinar thalamic nucleus in human temporal lobe seizures.
AB  - PURPOSE: Several animal studies suggest that the thalamus might be involved in
      the maintenance and propagation of epileptic seizures. However,
      electrophysiologic evidence for this implication in human partial epileptic
      seizures is still lacking. Considering the rich and reciprocal connectivity of
      the medial pulvinar (PuM) with the temporal lobe, we evaluated a potential
      participation of this thalamic nucleus in temporal lobe epilepsy (TLE). METHODS:
      The electrophysiologic activity of PuM was recorded during
      stereoelectroencephalographic exploration of spontaneous temporal lobe seizures
      in 14 patients referred for presurgical assessment of refractory TLE. RESULTS: We
      recorded PuM ictal activity in 80% of the 74 seizures that we analyzed. This
      activity was characterized by rhythmic slow-waves or rhythmic spikes (RSW-RS) or
      both or by low-voltage fast activity (LVFA) in 64% and 36% of seizures,
      respectively. RSW-RS occurred mostly in seizures arising from mesiotemporal
      structures, whereas LVFA was more frequently observed in seizures of neocortical
      origin. In the 15 seizures without PuM ictal activity, spreading of the seizure
      outside the onset zone never occurred, whereas it did in 78% of seizures with PuM
      ictal involvement. Discharge propagation was systematic when PuM involvement
      corresponded to LVFA, whatever the seizure onset zone was, whereas it represented
      only 66% of the seizures when PuM exhibited RSW-RS. CONCLUSIONS: This study shows
      that ictal changes in PuM activity are frequently observed during temporal lobe
      seizures and suggests that this thalamic nucleus might participate in their
      propagation.

PMID- 16417538
TI  - Identification of the epileptogenic tuber in patients with tuberous sclerosis: a
      comparison of high-resolution EEG and MEG.
AB  - PURPOSE: We compared epileptiform activity recorded with EEG and
      magnetoencephalography (MEG) in 19 patients with tuberous sclerosis complex (TSC)
      and epilepsy. METHODS: High-resolution (HR) EEG, HR-MEG, and 1.5-T MRI scans were
      performed. Epileptiform spikes were identified in EEG and MEG recordings offline
      by three observers. Spikes for which the interobserver agreement (spike
      consensus) was >0.40 were used for source localization with CURRYV 3.0 software.
      MUSIC analysis was performed. The distance between the source determined from EEG
      and MEG recordings and the border of the closest tuber was calculated and
      compared. RESULTS: Consensus spikes (kappa >0.4) were identified in 12 patients
      in the EEG recording and in 14 patients in the MEG recording. MEG sources were
      closer to tubers in all but one patient. Three patients underwent epilepsy
      surgery, two of whom are seizure free after complete resection of the tuber.
      CONCLUSIONS: In patients with TSC, epileptogenic sources identified on MEG are
      closer to the presumed epileptogenic tuber than are similar sources identified on
      EEG. Moreover, spike consensus is greater with MEG. Clear identification of the
      epileptogenic zone may offer opportunities for surgery in patients with TSC with
      intractable epilepsy.

PMID- 16417539
TI  - Refractory generalized seizures: response to corpus callosotomy and vagal nerve
      stimulation.
AB  - PURPOSE: The vagal nerve stimulator (VNS) and corpus callosotomy can reduce
      seizure frequency when seizures are refractory to medications. However, the
      efficacy and safety of these two procedures have not been compared. This study
      evaluates the two procedures for generalized seizures. METHODS: All patients with
      refractory generalized seizures (generalized tonic-clonic, tonic, or atonic) who
      underwent a corpus callosotomy (anterior or complete) (n = 53) without other
      forms of epilepsy surgery and those who underwent VNS placement (n = 25) were
      evaluated for this study. Seizure response and procedure complications were
      evaluated. RESULTS: For those with a corpus callosotomy and generalized tonic
      clonic seizures (n = 50), 79.5% had >or=50% decrease in the frequency of
      generalized tonic-clonic seizures, and 60% had >or=80% seizure reduction. For
      those with a VNS and generalized tonic-clonic seizures (n = 21), 50% had >or=50%
      seizure reduction, and 33% had >or=80% seizure reduction. Tonic and atonic
      seizures decreased after either VNS or a corpus callosotomy. The complication
      rate for corpus callosotomy was higher (21% all complications, 3.8% permanent)
      than that for VNS (8%; none permanent), but complications for both corpus
      callosotomy and VNS were rarely permanent. CONCLUSIONS: Both corpus callosotomy
      and VNS are effective in reducing generalized seizures. Corpus callosotomy is
      associated with greater efficacy but higher risk for complications, although
      these were generally transient.

PMID- 16417540
TI  - Ictal brain hyperperfusion contralateral to seizure onset: the SPECT mirror
      image.
AB  - PURPOSE: Ictal single-photon emission computed tomography (SPECT) may help
      localize the seizure-onset zone (SOZ) by detecting changes in regional cerebral
      blood flow induced by epileptic discharges. This imaging method also reveals
      hyperperfusions in areas of seizure propagation, including the hemisphere
      contralateral to the SOZ. We have studied the occurrence, the topography, and the
      clinical value of such contralateral ictal hyperperfusion areas (HPAs). METHODS:
      We examined data from presurgical evaluations of 36 consecutive patients with
      pharmacoresistant partial epilepsy of various localizations. Ictal and interictal
      SPECT examinations were made with 99mTc-ECD, and the scans were processed for
      coregistration, normalization, subtraction, and merging with MRI images. RESULTS:
      Contralateral HPAs were observed in 72% of the patients: 50% of mesiotemporal
      epilepsy cases with hippocampal sclerosis, 85.7% of the other mesiotemporal
      epilepsies, 85.7% of neocortical lateral temporal epilepsies, and 87.5% of
      extratemporal epilepsies. Contralateral HPAs were usually symmetrical to the SOZ,
      forming a mirror image, observed in 57.1% of the patients. They could be slightly
      asymmetrical in mesiotemporal epilepsies, perhaps because of the particular
      anatomic pathways linking temporal lobes. In neocortical epilepsies, they were
      located in the cortex homotopic to the SOZ. CONCLUSIONS: We show that the
      symmetrical nature of the mirror image usually does not disturb SPECT
      interpretation. It can confirm the location of the SOZ (11 patients) and even
      occasionally improve the precision of its definition (nine patients) by
      restraining several potential SOZ-related HPAs to a single one or by permitting a
      restricted localization of the SOZ in a large HPA.

PMID- 16417541
TI  - In vivo profiling of focal cortical dysplasia on high-resolution MRI with
      computational models.
AB  - PURPOSE: On MRI, focal cortical dysplasia (FCD) is characterized by a combination
      of increased cortical thickness, hyperintense signal within the dysplastic
      lesion, and blurred transition between gray and white matter (GM-WM). The visual
      identification of these abnormal characteristics may be difficult, and it is
      unclear to what degree these features occur among different FCD lesions. Our
      purpose was to investigate the pattern of occurrence of abnormal MRI
      characteristics in FCD by using a set of computational models and to generate
      quantitative lesion profiling. METHODS: A set of voxel-wise operators was applied
      to high-resolution 3D T1-weighted MRI in 23 patients with histologically proven
      FCD and 39 healthy controls, creating maps of GM thickness, maps of relative
      intensity highlighting areas with hyperintense signal, and maps of gradient
      magnitude modeling the GM-WM transition. All FCD lesions were segmented manually
      on the T1-weighted MRI. RESULTS: FCD volumes ranged from 734 mm3 to 80,726 mm3
      (mean, 8,629 mm3 +/- 16,238). The manually segmented FCD lesions were used to
      estimate features in the lesional area and to determine possible local variations
      of each feature by means of a histogram. In 78% of the patients, FCD lesions were
      characterized by simultaneous GM thickening, hyperintense signal, and blurring of
      the GM-WM transition. Moreover, in all patients, the FCD lesion had at least two
      of these three characteristics. CONCLUSIONS: The three features occurred
      regardless of the lesion volume, and they characterized not only large FCD
      lesions, but also subtle ones that had been overlooked by conventional radiologic
      inspection before surgery.

PMID- 16417542
TI  - Quantitative MRI biomarkers of cognitive morbidity in temporal lobe epilepsy.
AB  - PURPOSE: To determine the relation between neuropsychological morbidity,
      quantitative magnetic resonance imaging (MRI) measures of whole brain structure,
      and clinical seizure factors reflecting epilepsy cause, course, and treatment.
      METHODS: Quantitative MRI measurements of total (whole brain) cerebrospinal fluid
      (CSF) and gray- and white-matter volumes and clinical seizure features were
      examined in relation to summary indices of cognitive morbidity in 96 patients
      with temporal lobe epilepsy. MRI volumes were adjusted for intracranial volume
      (ICV), and cognitive scores were adjusted for age, education, and gender, based
      on a sample of 82 healthy controls. RESULTS: Whole-brain volumes (gray, white,
      and CSF) were abnormal in chronic temporal lobe epilepsy patients compared with
      controls and were related significantly to neuropsychological morbidity,
      especially total CSF. Statistical modeling demonstrated that markers of total
      atrophy (CSF) was the primary mediator of the relation between clinical seizure
      variables and neuropsychological morbidity. CONCLUSIONS: Quantitative
      measurements of overall brain abnormality (atrophy) in temporal lobe epilepsy are
      clinically meaningful markers that are associated with increased cognitive
      morbidity. These biomarkers appear to mediate the adverse effects of some
      clinical seizure variables on cognition.

PMID- 16417543
TI  - Cognitive functions in juvenile and adult patients with gelastic epilepsy due to
      hypothalamic hamartoma.
AB  - PURPOSE: To describe extend and severity of cognitive deficits in juvenile and
      adult patients with gelastic seizures and hypothalamic hamartoma (HH) and to
      analyze the impact of epilepsy-related variables on cognitive performance.
      METHODS: Thirteen juvenile and adult patients (mean age, 25 years; seven men)
      underwent comprehensive neuropsychological testing assessing intellectual
      performance, attention and executive functions, verbal and visual memory, and
      visuospatial abilities. RESULTS: Intellectual abilities ranged from moderate
      mental retardation to good average performance; 54% of the patients displayed
      below-average global intellectual abilities. Attentional and executive functions
      were impaired in 23% to 46% of the patients. Below-average visuospatial
      capabilities were observed in 39% of the cases. Memory functions were impaired
      regarding both visual (77%) and verbal learning (62%). Nonparametric correlation
      analysis revealed a significant relation between monthly partial seizure
      frequency and reduced cognitive flexibility and reduced performance in mental
      rotation. In addition, HH volume was significantly negatively correlated with
      cognitive flexibility, whereas age at onset and duration of epilepsy did not show
      significant correlation to cognitive performance. CONCLUSIONS: More than half of
      the adult patients with gelastic seizures and HH displayed deficits in a broad
      range of cognitive functions, expressed mostly in visual and verbal learning and
      memory. Some of the deficits could be shown to correlate with disease-related
      characteristics representing the severity of the epilepsy or the size of the
      underlying lesion. These findings prompt for a longitudinal investigation of the
      development of these cognitive deficits to analyze further the relevant factors
      contributing to this wide spectrum of cognitive impairments.

PMID- 16417544
TI  - Hippocampal sclerosis in children with lesional epilepsy is influenced by age at
      seizure onset.
AB  - PURPOSE: Hippocampal sclerosis (HS) is the most common lesion underlying drug
      resistant temporal lobe epilepsy. Whether HS is a developmental or acquired
      pathology remains unclear. Whereas HS has been causally linked to prolonged
      febrile convulsions in childhood, evidence also exists that it may coexist with
      extrahippocampal abnormalities, the concept of "dual pathology." The aims of this
      study were to address whether hippocampal abnormality consistent with HS (a)
      occurs in children with lesional extrahippocampal epilepsy, (b) is more commonly
      seen in association with developmental rather than acquired extrahippocampal
      pathologies, and (c) whether any effect of age at seizure onset is found on the
      occurrence of HS in lesional extrahippocampal epilepsy. METHODS: Clinical and
      histopathologic data of patients having resective surgery for extrahippocampal
      epilepsy that included the hippocampus were investigated. RESULTS: Twenty-nine
      children were retrospectively included in this study, and 21 (72%) of 29 were
      found to have a hippocampal abnormality consistent with HS. No relation was noted
      between developmental or acquired extrahippocampal pathologies and the presence
      of hippocampal abnormality. Children with normal hippocampi on visual histologic
      assessment had a significantly younger age at seizure onset (p < 0.001). Duration
      of epilepsy was not correlated with the presence of hippocampal abnormality.
      CONCLUSIONS: Hippocampal abnormalities are seen in similar proportions with both
      acquired and developmental extra-hippocampal pathologies, suggesting that these
      abnormalities are the result of seizures from the focus that is remote from the
      hippocampus. In addition, children who have their initial seizure at an early age
      are less likely to develop seizure-induced hippocampal injury.

PMID- 16417545
TI  - Hippocampal and thalamic diffusion abnormalities in children with temporal lobe
      epilepsy.
AB  - PURPOSE: Previous studies using diffusion MRI in patients with temporal lobe
      epilepsy have shown abnormal water diffusion in the hippocampus. Because thalamus
      and lentiform nuclei are considered important for the regulation of cortical
      excitability and seizure propagation, we analyzed diffusion tensor imaging (DTI)
      abnormalities in these subcortical structures and in hippocampus of children with
      partial epilepsy with and without secondary generalization. METHODS: Fourteen
      children with partial epilepsy involving the temporal lobe underwent MRI
      including a DTI sequence. Fractional anisotropy (FA) and apparent diffusion
      coefficient (ADC) values were obtained in the hippocampus, thalamus, and
      lentiform nucleus, and compared with DTI data of 14 control children with no
      epilepsy, as well as glucose positron emission tomography (PET) findings.
      RESULTS: Decreased FA (p < 0.001) and increased ADC (p = 0.003) values were found
      in the hippocampi ipsilateral to the seizure focus. Significant FA decreases (p =
      0.002) also were seen in the contralateral hippocampi, despite unilateral seizure
      onset and excellent surgical outcome in patients who underwent surgery. ADC
      values showed a trend for increase in the thalami ipsilateral to the epileptic
      focus in the seven children with secondarily generalized seizures (p = 0.09). No
      group differences of ADC or FA were found in the lentiform nuclei. The DTI
      variables did not correlate with regional glucose metabolism in any of the
      structures analyzed. CONCLUSIONS: Increased ADC values in hippocampus can assist
      in lateralizing the seizure focus, but decreased FA in the contralateral
      hippocampus suggests that it too may be dysfunctional despite unilateral seizure
      onset. Less-robust thalamic abnormalities of water diffusion in patients with
      secondarily generalized seizures suggest secondary involvement of the thalamus,
      perhaps due to recruitment of this structure into the epileptic network; however,
      this must be confirmed in a larger population. DTI appears to be a sensitive
      method for detection abnormalities in children with partial epilepsy, even in
      structures without apparent changes on conventional MRI.

PMID- 16417546
TI  - Efficacy of dexamathasone on cerebral swelling and seizures during subdural grid
      EEG recording in children.
AB  - PURPOSE: To evaluate the impact of steroid treatment on cerebral swelling and
      seizures during subdural grid EEG (SGEEG) monitoring. METHODS: We reviewed data
      from 37 pediatric patients with intractable epilepsy who underwent SGEEG
      monitoring and divided the patients into those who received dexamethasone and
      those who did not. We then correlated administration of steroids to incidence of
      cerebral swelling on computed tomography (CT) scans and to frequency of seizures
      during SGEEG. RESULTS: Twenty-three patients received dexamethasone
      prophylactically every 6 hours (dosage range, 1-7.5 mg; mean, 3.2 mg) from the
      first day of SGEEG placement (group A); 14 patients received no dexamethasone
      (group B). Eight (21.6%) of 37 patients experienced cerebral swelling on CT: two
      (9%) were in group A, and six (42.9%) were in group B (p < 0.05). SGEEG
      monitoring time for recording habitual seizures that localized cortical areas for
      surgical excision was longer in group A (1-6 days; mean, 3.0) than it was in
      group B (1-3 days; mean, 2.2), (p < 0.05). Habitual seizures were recorded in 36
      patients. One group A patient experienced obtundation due to cerebral swelling,
      and monitoring in this patient was discontinued. CONCLUSIONS: The prophylactic
      administration of steroids to pediatric patients during SGEEG monitoring is
      efficacious for reducing cerebral swelling. Although it decreases the frequency
      of habitual seizures and increases seizure-monitoring time, dexamethasone reduces
      the risk of complications from cerebral swelling during the SGEEG procedure.

PMID- 16417547
TI  - Long-term follow-up of patients with benign partial epilepsy in infancy.
AB  - PURPOSE: The aim of this study was to investigate the long-term outcome of
      children with benign partial epilepsy in infancy (BPEI). METHODS: A telephone
      interview survey using a structured questionnaire was conducted with patients who
      were diagnosed as having possible BPEI at age 2 years and who were 8 years or
      older at the time of the survey. The data from 39 of 48 patients were available.
      The median age at the time of the survey was 11.3 years; 18 boys and 21 girls
      were included. RESULTS: Three patients had a recurrence of unprovoked seizure
      beyond age 2 years. Four patients had cognitive problems (mild mental retardation
      in three and Asperger syndrome in one). An association of paroxysmal kinesigenic
      choreoathetosis was observed in three patients, and another three had experienced
      seizures associated with mild gastroenteritis. Major behavioral problems were not
      recognized in any patients. Four patients were excluded from having definite BPEI
      at age 5 years, and another two were excluded for having definite BPEI at the
      last follow-up. Eventually, 33 of 39 patients were categorized as having definite
      BPEI beyond 8 years of age. CONCLUSIONS: A large majority of patients diagnosed
      as possibly having BPEI at age 2 years did not have a recurrence of unprovoked
      seizures and cognitive problems beyond 8 years of age.

PMID- 16417549
TI  - Epilepsy in Colombia: epidemiologic profile and classification of epileptic
      seizures and syndromes.
AB  - PURPOSE: A national study was performed in Colombia to determine the general and
      regional prevalence of epilepsy, clinical profiles, seizure types, and clinical
      syndromes. METHODS: Based on the National Epidemiological Study of Neurological
      Diseases (EPINEURO), we evaluated and followed up for 1 year all the subjects
      with epilepsy from the National Sample. Clinical profiles were further assessed.
      Seizure types and epilepsy syndromes were established according to the
      international classifications. RESULTS: General prevalence was found to be 11.3
      per 1,000, with little variation among regions, except the eastern region, where
      prevalence was 23 per 1,000; prevalence for active epilepsy was 10.1 per 1,000.
      Women have a slightly greater (not statistically significant) risk. Most seizures
      are focal (partial), frequently with secondary generalization. The most frequent
      epilepsy syndrome encountered was partial symptomatic/cryptogenic (80%). Epilepsy
      onset in Colombia occurs most frequently in childhood. CONCLUSIONS: Prevalence
      rates of epilepsy in Colombia are similar to those reported in nations with
      comparable developmental status and have diminished over time. The study presents
      the distribution of seizures and syndromes. The most frequent types are focal
      syndromes.

PMID- 16417548
TI  - Community-based, prospective, controlled study of obstetric and neonatal outcome
      of 179 pregnancies in women with epilepsy.
AB  - PURPOSE: This study evaluated obstetric and neonatal outcome in a community-based
      cohort of women with active epilepsy (WWAE) compared with the general pregnant
      population receiving modern obstetric care. METHODS: We reviewed the total
      population who gave birth between January 1989 and October 2000 at Kuopio
      University Hospital. Obstetric, demographic, and epilepsy data were collected
      prospectively from 179 singleton pregnancies of women with epilepsy and from
      24,778 singleton pregnancies of unaffected controls. The obstetric data from the
      pregnancy register was supplemented with detailed neurologic data retrieved from
      the medical records. The data retrieved were comprehensive because of a follow-up
      strategy according to a predecided protocol. RESULTS: During pregnancy, the
      seizure frequency was unchanged, or the change was for the better in the majority
      (83%) of the patients. We found no significant differences between WWAE and
      controls in the incidence of preeclampsia, preterm labor, or in the rates of
      caesarean sections, perinatal mortality, or low birth weight. However, the rate
      of small-for-gestational-age infants was significantly higher, and the head
      circumference was significantly smaller in WWAE. Apgar score at 1 min was lower
      in children of WWAE, and the need for care in the neonatal ward and neonatal
      intensive care were increased as compared with controls. The frequency of major
      malformations was 4.8% (-0.6-10.2%; 95% confidence interval) in the 127 children
      of WWAE. CONCLUSIONS: Pregnancy course is uncomplicated and neonatal outcome is
      good in the majority of cases when a predecided protocol is used for the follow
      up of WWAE in antenatal and neurologic care. Long-term follow-up of the
      neurologic and cognitive development of the children of WWAE is still needed.

PMID- 16417550
TI  - Somatosensory auras in refractory temporal lobe epilepsy.
AB  - PURPOSE: To determine the prevalence, manifestations, lateralizing value, and
      surgical prognostic value of somatosensory auras (SSAs) in patients with
      refractory temporal lobe epilepsy (TLE). METHODS: Eighty-one consecutive patients
      undergoing temporal lobectomy for refractory complex-partial seizures were
      screened for SSAs. The characteristics of the somatosensory phenomena, occurrence
      of other aura types, seizure semiology, findings of EEG and imaging studies,
      temporal lobe neuropathology, and postoperative seizure outcome were determined
      in each patient with SSAs. RESULTS: Nine (11%) of 81 patients with refractory
      temporal lobe seizures reported distinct SSAs as part of their habitual seizures.
      The most common manifestation of SSAs was tingling (eight of nine, 89%), but
      sensory loss (one of nine, 11%) and pain (one of nine, 11%) also were reported.
      Five patients had unilateral somatosensory symptoms, and four patients had
      bilateral somatosensory symptoms. Seizure origin was in the contralateral
      temporal lobe in four (80%) of five patients with unilateral SSAs, including all
      patients with unilateral SSAs affecting a limb. Partial temporal lobe resection
      produced complete seizure remission in all nine (100%) patients 1 year after
      surgery and in seven (78%) of nine patients 2 years after surgery. CONCLUSIONS:
      SSAs occur more frequently than previously appreciated in patients with
      refractory temporal lobe seizures and usually manifest as either unilateral or
      bilateral tingling. In patients with temporal lobe seizures, unilateral SSAs
      involving a limb suggest a seizure origin in the contralateral temporal lobe. The
      surgical outcome of TLE patients with SSAs is favorable. Thus the presence of
      SSAs should not serve as a deterrent to temporal lobe resection in patients with
      clearly defined TLE.

PMID- 16417551
TI  - Beta activity in status epilepticus.
AB  - Focal beta activity on scalp EEG is a rare seizure pattern that has most
      extensively been studied in patients undergoing evaluation for epilepsy surgery.
      However, ictal beta activity is uncommon beyond this population and has not been
      reported in human status epilepticus. We observed ictal focal beta activity as
      the predominant seizure pattern in a patient with refractory status epilepticus.
      Continuous left temporal beta activity clinically correlated with complex partial
      semiology on video-EEG.

PMID- 16417552
TI  - Mutation in filamin A causes periventricular heterotopia, developmental
      regression, and West syndrome in males.
AB  - PURPOSE: Familial periventricular heterotopia (PH) represents a disorder of
      neuronal migration resulting in multiple gray-matter nodules along the lateral
      ventricular walls. Prior studies have shown that mutations in the filamin A
      (FLNA) gene can cause PH through an X-linked dominant pattern. Heterozygotic
      female patients usually remain asymptomatic until the second or third decade of
      life, when they may have predominantly focal seizures, whereas hemizygotic male
      fetuses typically die in utero. Recent studies have also reported mutations in
      FLNA in male patients with PH who are cognitively normal. We describe PH in three
      male siblings with PH due to FLNA, severe developmental regression, and West
      syndrome. METHODS: The study includes the three affected brothers and their
      parents. Video-EEG recordings and magnetic resonance image (MRI) scanning were
      performed on all individuals. Mutations for FLNA were detected by using
      polymerase chain reaction (PCR) on genomic DNA followed by single-stranded
      conformational polymorphism (SSCP) analysis or sequencing. RESULTS: Two of the
      siblings are monozygotic twins, and all had West syndrome with hypsarrhythmia on
      EEG. MRI of the brain revealed periventricular nodules of cerebral gray-matter
      intensity, typical for PH. Mutational analyses demonstrated a cytosine-to
      thymidine missense mutation (c. C1286T), resulting in a threonine-to-methionine
      amino acid substitution in exon 9 of the FLNA gene. CONCLUSIONS: The association
      between PH and West syndrome, to our knowledge, has not been previously reported.
      Males with PH have been known to harbor FLNA mutations, although uniformly, they
      either show early lethality or survive and have a normal intellect. The current
      studies show that FLNA mutations can cause periventricular heterotopia,
      developmental regression, and West syndrome in male patients, suggesting that
      this type of FLNA mutation may contribute to severe neurologic deficits.

PMID- 16417553
TI  - Beta-ureidopropionase deficiency presenting with febrile status epilepticus.
AB  - Beta-ureidopropionase is the third enzyme in the catabolic pathway of uracil and
      thymine. To date, only three other patients are reported with this inborn error
      of metabolism. We report the clinical presentation of a male patient who
      presented at the age of 4 months after an ALTE-like event (ALTE = acute life
      threatening event) with febrile status epilepticus. Such a clinical presentation
      has not been reported before in this condition. Diagnosis was based on
      biochemical, enzymatic and molecular studies. MRI (magnetic resonance imaging) at
      the age of 11 months demonstrated large subdural hematomata and global
      supratentorial atrophy. At that time the patient showed severe psychomotor
      retardation with muscular hypotonia, extremely limited visual contact and poorly
      controlled epilepsy. CONCLUSIONS: Pyrimidine degradation defects should be
      included in the differential diagnosis of convulsions, (febrile) status
      epilepticus, psychomotor retardation and possibly also ALTE-like events.

PMID- 16417555
TI  - Occipital seizures and visual evoked potentials.

PMID- 16417554
TI  - A novel SCN2A mutation in family with benign familial infantile seizures.
AB  - Benign familial infantile seizures (BFIS) is a clinical entity characterized by
      focal seizures with or without secondary generalization, occurring mostly in
      clusters, and usually first seen between 4 and 8 months of life. Psychomotor
      development is normal, and seizures usually resolve within the first year of
      life. BFIS is a genetically heterogenous condition with loci mapped to
      chromosomes 19 and 16. Mutations in the voltage-gated sodium channel alpha2
      subunit (SCN2A) gene on chromosome 2 were recently identified in families
      affected by neonatal and infantile seizures (benign familial neonatal-infantile
      seizures, BFNIS) with typical onset before 4 months of life. The identification
      of SCN2A mutations in families with only infantile seizures indicated that BFNIS
      and BFIS show overlapping clinical features. We report a pedigree showing three
      affected individuals over three generations. All subjects experienced clusters of
      focal seizures with or without secondary generalization and onset between 4 and
      12 months of life. Response to antiepileptic drugs and the outcome were good. No
      subjects had other forms of epilepsy later in the life. Neonatal or febrile
      seizures did not occur in the family. Genetic study in this family revealed a
      novel heterozygous mutation c.3003 T>A in the SCN2A gene. Comparative analysis of
      different sodium channel alpha subunits indicates that the mutated residue is
      highly conserved throughout the evolution, suggesting an important functional
      role for this domain. Additional families with the infantile form of benign
      familial seizures should be investigated to corroborate that BFIS and BFNIS may
      share the same genetic abnormality.

PMID- 16417557
TI  - Nonconvulsive status epilepticus after temporal lobectomy.

PMID- 16417559
TI  - Molecular diagnostics of non-small cell lung cancer using mediastinal lymph nodes
      sampled by endoscopic ultrasound-guided needle aspiration.
AB  - Non-small cell lung cancer is a common cancer with significant mortality.
      Accurate and early staging of this cancer has a significant impact on outcome.
      Endoscopic ultrasound-guided fine needle aspiration of involved mediastinal lymph
      nodes is critical for staging. Several molecular markers have been identified
      recently in association with non-small cell carcinoma of the lung that are
      promising to make early detection of metastatic disease more reliable.

PMID- 16417560
TI  - Endoscopic ultrasound-guided fine needle aspiration cytology of pancreatic
      neuroendocrine tumours: cytomorphological and immunocytochemical evaluation.
AB  - OBJECTIVES: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is
      increasingly used in preoperative localization and diagnosis of pancreatic
      neoplasms including neuroendocrine tumours (NETs). The objective of the present
      study was to identify the cytological features of pancreatic NETs obtained by EUS
      FNA. METHODS: The study group consisted of nine cases of pancreatic tumours
      correctly diagnosed or strongly suggestive of NETs based on EUS-FNA. Cytological
      smears were retrospectively reviewed. The clinical data and immunocytochemical
      stains applied to the cell block preparations were also reviewed and examined.
      RESULTS: All cases except one showed characteristic cytomorphological features
      sufficient for their recognition and separation from pancreatic adenocarcinoma
      and other lesions. The most helpful cytological features that facilitated the
      cytological diagnosis of NET were a richly cellular aspirate with a monotonous,
      poorly cohesive population of small cells with a speckled or dusty chromatin
      pattern and plasmacytoid morphology. The neuroendocrine differentiation of these
      tumours was further confirmed by immunocytochemistry. CONCLUSION: EUS-FNA is a
      valuable method in the recognition of pancreatic NETs. By adherence to the
      characteristic cytomorphological criteria of pancreatic NET together with
      collection of suitable material for ancillary immunocytochemical stains,
      cytopathologists could reach a correct diagnosis in most instances.

PMID- 16417561
TI  - Impact of cytopathologist expert on diagnosis and treatment of pancreatic lesions
      in current clinical practice. A series of 106 endoscopic ultrasound-guided fine
      needle aspirations.
AB  - OBJECTIVES: To evaluate the role of a cytopathologist expert in interpreting
      difficult pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS
      FNA) in terms of impact on diagnostic yield and therapy in current clinical
      practice. METHODS: Retrospective study of 106 EUS-FNA performed between January
      2002 and September 2004. Forty-seven cases of difficult interpretation by the
      local cytopathologist were mailed to an expert cytopathologist. The final
      diagnosis was established by histology obtained by either surgery (n=30), non
      equivocal FNA (n=40) or core (n=8) biopsies, or by a mean follow-up of 14 months
      (n=28). RESULTS: EUS-FNA involved 68 solid lesions (SL). Specimens collected were
      adequate in 63%. The overall sensitivity of EUS-FNA for the diagnosis of
      malignancy of SL was 88% versus 72% for local cytopathologist and 89% for expert.
      EUS-FNA with the reevaluation by expert of 39 SL gave a therapeutic impact in 47%
      of SL. Thirty-eight cystic lesions (CL) were evaluated. Specimens collected were
      adequate for cytology in 84% of cases and for biochemistry in 79%. The
      sensitivity of imaging+EUS-FNA+/-biochemistry for the diagnosis of a surgical CL
      was 58% with a therapeutic impact in 39.5%. CONCLUSION: Pancreatic EUS-FNA is an
      easy technique for experienced endosonographers, which can be safely performed on
      an outpatient basis. The possibility of mailing difficult cases to an expert
      cytopathologist increases the diagnostic yield. In these circumstances, EUS-FNA
      has a therapeutic impact in current practice in nearly one out of two pancreatic
      lesions.

PMID- 16417562
TI  - Endoscopic ultrasound-guided tissue sampling by combined fine needle aspiration
      and trucut needle biopsy: a prospective study.
AB  - BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS
      FNA) has a diagnostic accuracy of 70-90%, depending on the site under evaluation.
      In order to improve EUS-guided tissue sampling a novel 19-gauge trucut-type
      needle has been designed to obtain core biopsies during EUS. We prospectively
      evaluated the safety and accuracy of EUS-FNA alone versus combined EUS-FNA and
      trucut needle biopsy (TNB) in patients referred to our Unit over a 3-year period.
      PATIENTS AND METHODS: A total of 159 patients underwent EUS-FNA alone (lesions<2
      cm) or the combination of both sampling modalities (lesions>or=2 cm). The
      adequacy of sampling, sensitivity, specificity and overall accuracies of EUS-FNA
      or EUS-TNB alone and combined EUS-FNA/TNB were determined. RESULTS: Adequate
      samples were obtained by EUS-FNA, EUS-TNB and EUS-FNA/TNB in 91%, 88% and 97% of
      patients, respectively. From the pancreas (n=83), adequate samples were obtained
      by FNA in 94% and by TNB in 81%, compared with 87% and 92% from non-pancreatic
      sites (n=76), respectively. The combination of both techniques resulted in more
      adequate samples from non-pancreatic cases than EUS-FNA alone (P=0.044). The
      specificity was 100%. Overall accuracy for EUS-FNA alone was 77%, for EUS-TNB
      alone 73% and for EUS-FNA/TNB 91% (P=0.008). For pancreatic sampling, the
      accuracy of EUS-FNA alone was 77%, for EUS-TNB alone 56% and for EUS-FNA/TNB 83%.
      For non-pancreatic sampling, the accuracy for EUS-FNA alone was 78%, for EUS-TNB
      alone 83% and for EUS-FNA/TNB 95% (P=0.006). The complication rate was 0.6%.
      CONCLUSIONS: Combined EUS-FNA/TNB for lesions>or=2 cm improves adequacy of
      sampling and diagnostic accuracy compared with either technique alone and is
      safe.

PMID- 16417563
TI  - Endoscopic ultrasound-guided fine needle aspiration of the pancreas:
      cytomorphological evaluation with emphasis on adequacy assessment, diagnostic
      criteria and contamination from the gastrointestinal tract.
AB  - OBJECTIVE: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has
      been proved to be safe, efficient and reliable in the diagnosis of pancreatic
      lesions. This study evaluated specimen adequacy, diagnostic criteria of various
      pancreatic neoplasms and contamination from the gastrointestinal (GI) tract.
      METHODS: EUS-guided FNA of the pancreas and subsequent surgical resections
      performed at the University of California Irvine Medical Center during February
      1996-October 2000 were retrospectively selected. Modified Papanicolaou staining
      method was used for immediate evaluation and cell block prepared. RESULTS: A
      total of 267 cases were available for review, including 147 (55.1%)
      positive/suspicious, 10 (3.7%) atypical, 96 (36.0%) negative and 14 (5.2%)
      unsatisfactory cases. Eighty-six (58.5%) positive/suspicious cases had
      histological confirmation and 12 (8.3%) had lymph node or distant metastases by
      cytology. Three atypical, two negative, and two unsatisfactory cases proved to
      have adenocarcinoma. Contamination from duodenum, stomach or pancreas was found
      in 77 positive/suspicious, three atypical and 90 negative cases. The sensitivity,
      specificity, diagnostic accuracy, positive and negative predictive values were
      94.6%, 100%, 95.6%, 100%, 82% respectively. CONCLUSIONS: EUS FNA is efficient and
      accurate in the diagnosis of pancreatic neoplasms in adequate samples.
      Contamination from the GI tract should be well recognized to avoid
      misinterpretation.

PMID- 16417564
TI  - Endoscopic ultrasound-guided FNA biopsy of bile duct and gallbladder: analysis of
      53 cases.
AB  - OBJECTIVE: Endoscopic retrograde cholangiopancreaticography (ERCP)-guided
      brushing has been the standard of practice for surveillance and detection of
      carcinoma in the biliary tree. Few studies have evaluated the role of endoscopic
      ultrasound-guided fine needle aspiration (EUS-FNA) in diagnosing clinically
      suspected cholangiocarcinoma. The role of this method in diagnosing clinically
      suspected gallbladder malignancies has not been extensively evaluated in the USA.
      This study investigates the role of EUS-FNA in the diagnosis of clinically
      suspected biliary tree and gallbladder malignancies in a large patient series.
      METHODS: EUS-FNAs were obtained from 46 bile duct and seven gallbladder lesions.
      On-site rapid interpretation was provided using air-dried Diff Quik stained
      smears. In addition, alcohol fixed Papanicoloau stained smears and Thin Prep
      preparations (Cytye Corp., Marlborough, MA, USA) were evaluated before providing
      a final cytological diagnosis. Tissue biopsies and/or clinical follow-up were
      used as the standards to determine operating characteristics for EUS-FNA.
      RESULTS: The mean ages for bile duct and gallbladder lesions were 66 years
      (range: 37-84 years), and 69 years (range 49-86 years), respectively. All cases
      diagnosed as suspicious/malignant on preliminary evaluation were confirmed on
      final cytological interpretation (27/27). The operating characteristics show that
      EUS-FNA is highly specific (100%) with sensitivity rates of 87% and 80% from
      clinically suspected malignancies of biliary tract and gallbladder, respectively.
      Sampling error in three cases and associated acute inflammation in two cases
      resulted in false-negative diagnoses. CONCLUSIONS: EUS-FNA of biliary tree and
      gallbladder carcinoma is highly specific and should be considered for evaluation
      of clinically suspicious lesions. Marked inflammation may result in false
      negative diagnoses.

PMID- 16417565
TI  - Primary cytological diagnosis of jaw tumour.

PMID- 16417566
TI  - Axillary mass without a primary tumour.

PMID- 16417568
TI  - Protein kinase C enhances glycine-insensitive desensitization of NMDA receptors
      independently of previously identified protein kinase C sites.
AB  - Protein kinase C (PKC) phosphorylates the NR1 and NR2A subunits of NMDARs at
      consensus sites located within their intracellular C-terminal tails. However, the
      functional consequences of these biochemical events are not well understood. In
      HEK293 cells expressing NR1/NR2A, activation of endogenous PKC by 4beta-phorbol
      12-myristate 13-acetate (PMA) increased NMDAR desensitization as evidenced by a
      reduced steady-state current without any change in peak. The effects of PMA on
      NMDAR-mediated responses were prevented by specific PKC inhibitors and were not
      mimicked by an inactive enantiomer of PMA. The effects of PMA were preserved
      despite mutagenesis of the major PKC sites on the NR1 subunit (S889A, S890A,
      S896A and S897A) or removal of the entire NR1 C-terminal tail (NR1(stop838)).
      When co-expressing NR1(stop838)/NR2A the effects of PMA could only be observed
      with agonist concentrations sufficient to induce glycine-insensitive
      desensitization. Moreover, the effects of PMA were observed in receptors composed
      of NR1/NR2A and NR1/NR2B, but not NR1/NR2C, a subunit combination in which
      desensitization is absent. The NR2 subunit dependence suggested that the actions
      of PMA might require specific PKC sites previously identified within NR2A.
      However, a C-terminal truncated form of NR2A (NR2A(stop905)) remained responsive
      to PMA. We conclude that activation of PKC increases NMDAR glycine-insensitive
      desensitization independently of previously identified sites located within the
      NR1 C-terminus and distal segment of the NR2A C-terminus.

PMID- 16417569
TI  - Copper (II) ions potently inhibit purified PrPres amplification.
AB  - The structural conversion of a host protein, PrP(C), into a protease-resistant
      isoform, PrPres, is the central event in the pathogenesis of infectious prion
      diseases. Purification of native PrP(C) molecules from hamster brain by either
      cation exchange or immobilized chelator chromatographic resins yielded
      preparations that supported efficient amplification of scrapie-induced PrPres in
      vitro. Using these purified preparations, we determined that in vitro PrPres
      amplification was inhibited by CuCl2 and ZnCl2 at IC50 concentrations of
      approximately 400 nm and 10 microM, respectively. In contrast, 100 microM MnCl2
      did not directly inhibit PrPres amplification or block Cu2+-mediated inhibition.
      Additionally, the inhibition of PrPres amplification by Cu2+ ions could be
      reversed by addition of either neocuproine or imidazole. Cu2+ inhibited PrPres
      amplification in both the presence and absence of stimulatory polyanion
      molecules. These biochemical findings support the hypothesis that Cu2+ ions might
      regulate the pathogenesis of prion diseases in vivo.

PMID- 16417570
TI  - Modifications of the iron-neuromelanin system in Parkinson's disease.
AB  - Parkinson's disease is a common neurodegenerative disorder with a mainly sporadic
      aetiology, although a number of monogenic familiar forms are known. Most of the
      motor symptoms are due to selective depletion of dopaminergic, neuromelanin
      containing neurones of the substantia nigra pars compacta. Neuromelanin is the
      dark insoluble macromolecule that confers the black (substantia nigra) or grey
      (locus coeruleus) colour to monoaminergic basal ganglia. In particular, nigral
      neurones are pigmented because of the accumulation of by-products of oxidative
      metabolism of the neurotransmitter dopamine. The occurrence of dopamine (and all
      the enzymatic machinery required for dopamine synthesis, re-uptake and disposal)
      and neuromelanin, and a large amount of iron ions that interact with them, makes
      dopaminergic nigral neurones peculiarly susceptible to oxidative stress
      conditions that, in turn, may become amplified by the iron-neuromelanin system
      itself. In this mini-review we describe biophysical evidence for iron
      neuromelanin modifications that support this hypothesis. Furthermore, we discuss
      the formation of the covalent linkage between alpha-synuclein and neuromelanin
      from the early stages of the disease.

PMID- 16417571
TI  - Intracellular trafficking in neurones and glia of fibroblast growth factor-2,
      fibroblast growth factor receptor 1 and heparan sulphate proteoglycans in the
      injured adult rat cerebral cortex.
AB  - The potent gliogenic and neurotrophic fibroblast growth factor (FGF)-2 signals
      through a receptor complex comprising high-affinity FGF receptor (FGFR)1 with
      heparan sulphate proteoglycans (HSPGs) as co-receptors. We examined the
      intracellular dynamics of FGF-2, FGFR1 and the HSPGs syndecan-2 and -3, glypican
      1 and -2, and perlecan in neurones and glia in and around adult rat cerebral
      wounds. In the intact cerebral cortex, FGF-2 and FGFR1 mRNA and protein were
      constitutively expressed in astrocytes and neurones respectively. FGF-2 protein
      was localized exclusively to astrocyte nuclei. After injury, expression of FGF-2
      mRNA was up-regulated only in astrocytes, whereas FGFR1 mRNA expression was
      increased in both glia and neurones, a disparity indicating that FGF-2 may act as
      a paracrine and autocrine factor for neurones and glia respectively. FGF-2
      protein localized to both cytoplasm and nuclei of injury-responsive neurones and
      glia. There was weak or no staining of HSPGs in the normal cerebral neuropil and
      glia nuclei, with a few immunopositive neurones. Specific HSPGs responded to
      injury by differentially co-localizing with trafficked intracellular FGF-2 and
      FGFR1. The spatiotemporal dynamics of FGF-2-FGFR1-HSPG complex formation implies
      a role for individual HSPGs in regulating FGF-2 storage, nuclear trafficking and
      cell-specific injury responses in CNS wounds.

PMID- 16417574
TI  - Methamphetamine-induced spectrin proteolysis in the rat striatum.
AB  - Methamphetamine (METH) is a widely abused psychostimulant. Multiple high doses of
      METH cause long-term toxicity to dopamine (DA) and serotonin (5-HT) nerve
      terminals in the brain, as evidenced by decreases in DA and 5-HT content,
      decreases in tyrosine and tryptophan hydroxylase activities, decreases in DA and
      5-HT re-uptake sites, and nerve terminal degeneration. Multiple high doses of
      METH are known to elicit a rapid increase in DA release and hyperthermia.
      Although METH also produces a delayed and sustained rise in glutamate, no studies
      have shown whether METH produces structural evidence of excitotoxicity in
      striatum, or identified the receptors that mediate this toxicity directly,
      independent of alterations in METH-induced hyperthermia. These experiments
      investigated whether METH can cause excitotoxicity as evidenced by cytoskeletal
      protein breakdown in a glutamate receptor-dependent manner. METH increased
      calpain-mediated spectrin proteolysis in the rat striatum 5 and 7 days after METH
      administration without affecting caspase 3-dependent spectrin breakdown. This
      effect was completely blocked with the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor antagonist, GYKI 52466, but not the NMDA
      receptor antagonist, MK-801. However, AMPA or NMDA receptor antagonism did not
      attenuate the METH-induced depletions of the dopamine transporter (DAT).
      Independent mechanisms involved in mediating spectrin proteolysis and DAT protein
      loss are discussed.

PMID- 16417575
TI  - The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of
      A beta precursors.
AB  - The presenilin (PS)/gamma-secretase system promotes production of the A beta (A
      beta) peptides by mediating cleavage of amyloid precursor protein (APP) at the
      gamma-sites. This system is also involved in the processing of type-I
      transmembrane proteins, including APP, cadherins and Notch1 receptors, at the
      epsilon-cleavage site, resulting in the production of peptides containing the
      intracellular domains (ICDs) of the cleaved proteins. Emerging evidence shows
      that these peptides have important biological functions, raising the possibility
      that their inhibition by gamma-secretase inhibitors may be detrimental to the
      cell. Here, we show that peptide E-Cad/CTF2, produced by the PS1/gamma-secretase
      processing of E-cadherin, promotes the lysosomal/endosomal degradation of the
      transmembrane APP derivatives, C99 and C83, and inhibits production of the APP
      ICD (AICD). In addition, E-Cad/CTF2 decreases accumulation of total secreted A
      beta. These data suggest a novel method to promote the non-amyloidogenic
      degradation of A beta precursors and to inhibit A beta production.

PMID- 16417576
TI  - Altered neuropeptide processing in prefrontal cortex of Cpe (fat/fat) mice:
      implications for neuropeptide discovery.
AB  - The biosynthesis of most neuropeptides and peptide hormones requires a
      carboxypeptidase such as carboxypeptidase E, which is inactive in Cpe(fat/fat)
      mice due to a naturally occurring point mutation. To assess the role of
      carboxypeptidase E in the processing of peptides in the prefrontal cortex, we
      used a quantitative peptidomics approach to examine the relative levels of
      peptides in Cpe(fat/fat) versus wild-type mice. Peptides representing internal
      fragments of prohormones and other secretory pathway proteins were decreased two-
      to 10-fold in the Cpe(fat/fat) mouse prefrontal cortex compared with wild-type
      tissue. Degradation fragments of cytosolic proteins showed no major differences
      between Cpe(fat/fat) and wild-type mice. Based on this observation, a search
      strategy for neuropeptides was performed by screening for peptides that decreased
      in the Cpe(fat/fat) mouse. Altogether, 32 peptides were identified, of which
      seven have not been previously reported. The novel peptides include fragments of
      VGF, procholecystokinin and prohormone convertase 2. Interestingly, several of
      the peptides do not fit with the consensus sites for prohormone convertase 1 and
      2, raising the possibility that another endopeptidase is involved with their
      biosynthesis. Taken together, these findings support the proposal that
      carboxypeptidase E is the major, but not the only, peptide-processing
      carboxypeptidase and also demonstrate the feasibility of searching for novel
      peptides based on their decrease in Cpe(fat/fat) mice.

PMID- 16417577
TI  - Galanin attenuates cyclic AMP regulatory element-binding protein (CREB)
      phosphorylation induced by chronic morphine and naloxone challenge in Cath.a
      cells and primary striatal cultures.
AB  - Repeated morphine administration leads to molecular alterations of the neural
      circuitry in the locus coeruleus and nucleus accumbens. These changes include
      increased activity of several components of the cAMP signaling pathway that are
      thought to be associated with psychological and somatic signs of opiate
      withdrawal. The neuropeptide galanin has been shown to attenuate cAMP signaling
      in multiple cell types. The current study demonstrates that acute galanin
      treatment blocks the consequences of increased cAMP signaling following chronic
      opiate administration and withdrawal in Cath.a cells and primary cultures of
      striatal neurons as measured by phosphorylation of the transcription factor cAMP
      regulatory element-binding protein (CREB). In addition, galanin-mediated
      attenuation of CREB phosphorylation is independent of galanin-induced
      extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in Cath.a cells.
      These data suggest that galanin receptors may serve as an additional potential
      therapeutic target for the treatment of opiate withdrawal.

PMID- 16417578
TI  - Hydrogen ion concentration differentiates effects of methamphetamine and dopamine
      on transporter-mediated efflux.
AB  - Methamphetamine (METH) causes release of stored intracellular dopamine (DA). We
      explored the interactions of METH with the recombinant human vesicular monoamine
      (hVMAT2) and/or human DA transporters (hDAT) in transfected mammalian (HEK293)
      cells and compared the findings with those for DA. In 'static' release assays at
      37 degrees C, less than 20% of pre-loaded [(3)H]DA was lost after 60 min, while
      nearly 80% of pre-loaded [(3)H]METH was lost at 37 degrees C under non-stimulated
      conditions. Results obtained by measuring substrate release using a superfusion
      apparatus revealed an even greater difference in substrate efflux. At pH 7.4,
      nearly all of the pre-loaded [(3)H]METH was lost after just 6 min, compared with
      the loss of 70-80% of pre-loaded [(3)H]DA (depending on cell type) after
      superfusion for 32 min. Increasing the extracellular pH from 7.4 to 8.6 had
      opposite effects on [(3)H]DA and [(3)H]METH retention. At pH 8.6, [(3)H]METH was
      retained more effectively by both hDAT and hDAT-hVMAT2 cells, compared with
      results obtained at extracellular pH 7.4. [(3)H]DA, however, was more effectively
      retained at pH 7.4 than at pH 8.6. These data suggest that DA and METH interact
      differently with the DAT and VMAT2, and require different H(+) concentrations to
      exert their effects.

PMID- 16417579
TI  - Alternative splicing of human metabotropic glutamate receptor 3.
AB  - The metabotropic glutamate receptor 3 (GRM3, mGluR3) is important in regulating
      synaptic glutamate. Here, we report the existence of three splice variants of
      GRM3 in human brain arising from exon skipping events. The transcripts are
      expressed in prefrontal cortex, hippocampus and cerebellum, and in B
      lymphoblasts. We found no evidence for alternative splicing of GRM2. The most
      abundant GRM3 variant lacks exon 4 (GRM3Delta4). In silico translation analysis
      of GRM3Delta4 predicts a truncated protein with a conserved extracellular ligand
      binding domain, absence of a seven-transmembrane domain, and a unique 96-amino
      acid C-terminus. When expressed in rat hippocampal neurons, GRM3Delta4 is
      translated into a 60 kDa protein. Immunostaining and cell fractionation data
      indicate that the truncated protein is primarily membrane-associated. An antibody
      developed against the GRM3Delta4 C-terminus detects a protein of approximately 60
      kDa in human brain lysates and in B lymphoblasts, suggesting translation of
      GRM3Delta4 in vivo. The existence of the GRM3Delta4 isoform is relevant in the
      light of the reported association of non-coding single nucleotide polymorphisms
      (SNPs) in GRM3 with schizophrenia, and with the potential of GRM3 as a
      therapeutic target for several neuropsychiatric disorders.

PMID- 16417580
TI  - Characterization of the REST/NRSF-interacting LIM domain protein (RILP):
      localization and interaction with REST/NRSF.
AB  - We previously identified a nuclear envelope protein repressor element-1 silencing
      transcription factor (REST)/neuron-restrictive silencer factor (NRSF)-interacting
      Lin-11, Isl-1 and Mec-3 (LIM) domain protein (RILP) that we proposed functions in
      the nuclear translocation of the transcriptional repressor REST/NRSF. In this
      study we assessed the functionality of the prenylation motif, protein kinase A
      (PKA) phosphorylation sites and nuclear localization sequences (NLSs) of RILP.
      [(3)H]-mevalonolactone labeled endogenous RILP, showing that RILP is indeed
      prenylated, while phosphorylation analysis showed that the two PKA sites are
      phosphorylated. Blocking RILP prenylation, mutating the NLSs or mutating the PKA
      phosphorylation sites caused RILP to mislocalize to the cytosol. Concurrent with
      this mislocalization of RILP, REST/NRSF and REST4, which are normally found in
      the nucleus, co-localized in the cytosol with the RILP mutants. This provides
      additional evidence that RILP interacts with REST/NRSF and REST4 in vivo, and is
      involved in the nuclear localization of REST/NRSF and REST4. Reporter gene
      analysis using the promoter region of the human cholinergic gene locus revealed
      that these RILP mutants prevented repression of the reporter gene. By trapping
      REST/NRSF in the cytosol, the RILP mutants prevented translocation to the nucleus
      where REST/NRSF binds to an RE-1/NRSE element to repress gene transcription.
      These results show that RILP is required for REST/NRSF nuclear targeting and
      function.

PMID- 16417581
TI  - Wild-type huntingtin protects neurons from excitotoxicity.
AB  - Huntingtin is a caspase substrate, and loss of normal huntingtin function
      resulting from caspase-mediated proteolysis may play a role in the pathogenesis
      of Huntington disease. Here we tested the hypothesis that increasing huntingtin
      levels protect striatal neurons from NMDA receptor-mediated excitotoxicity.
      Cultured striatal neurons from yeast artificial chromosome (YAC)18 transgenic
      mice over-expressing full-length wild-type huntingtin were dramatically protected
      from apoptosis and caspase-3 activation compared with cultured striatal neurons
      from non-transgenic FVB/N littermates and YAC72 mice expressing mutant human
      huntingtin. NMDA receptor activation induced by intrastriatal injection of
      quinolinic acid initiated a form of apoptotic neurodegeneration within the
      striatum of mice that was associated with caspase-3 cleavage of huntingtin in
      neurons and astrocytes, decreased levels of full-length huntingtin, and the
      generation of a specific N-terminal caspase cleavage product of huntingtin. In
      vivo, over-expression of wild-type huntingtin in YAC18 transgenic mice conferred
      significant protection against NMDA receptor-mediated apoptotic
      neurodegeneration. These data provide in vitro and in vivo evidence that
      huntingtin may regulate the balance between neuronal survival and death following
      acute excitotoxic stress, and that the levels of huntingtin may modulate neuronal
      sensitivity to excitotoxic neurodegeneration. We suggest that further study of
      huntingtin's anti-apoptotic function will contribute to our understanding of the
      pathogenesis of Huntingdon's disease and provide insights into the selective
      vulnerability of striatal neurons to excitotoxic cell death.

PMID- 16417582
TI  - Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C
      adrenergic receptors.
AB  - The norepinephrine transporter (NET) is responsible for the rapid removal of
      norepinephrine released from sympathetic neurons; this release is controlled by
      inhibitory alpha(2)-adrenergic receptors (alpha(2)ARs). Long-term inhibition of
      the NET by antidepressants has been reported to change the density and function
      of pre- and postsynaptic ARs, which may contribute to the antidepressant effects
      of NET inhibitors such as desipramine. NET-deficient (NET-KO) mice have been
      described to behave like antidepressant-treated mice. By means of quantitative
      real-time PCR we show that mRNAs encoding the alpha(2A)-adrenergic receptor
      (alpha(2A)AR) and the alpha(2C)-adrenergic receptor (alpha(2C)AR) are up
      regulated in the brainstem, and that alpha(2C)AR mRNA is also elevated in the
      hippocampus and striatum of NET-KO mice. These results were confirmed at the
      protein level by quantitative autoradiography. The NET-KO mice showed enhanced
      binding of the selective alpha(2)AR antagonist [(3)H]RX821002 in several brain
      regions. Most robust increases (20-25%) in alpha(2)AR expression were observed in
      the hippocampus and in the striatum. Significant increases (16%) were also seen
      in the extended amygdala and thalamic structures. In an 'in vivo' test, the
      alpha(2)AR agonist clonidine (0.1 mg/kg) caused a significantly greater reduction
      of locomotor activity in NET-KO mice than in wild-type mice, showing the
      relevance of our findings at the functional level.

PMID- 16417583
TI  - Intrinsic and extrinsic erythropoietin enhances neuroprotection against ischemia
      and reperfusion injury in vitro.
AB  - This study was designed to investigate the neuroprotective effect of intrinsic
      and extrinsic erythropoietin (EPO) against hypoxia/ischemia, and determine the
      optimal time-window with respect to the EPO-induced neuroprotection. Experiments
      were conducted using primary mixed neuronal/astrocytic cultures and neuron-rich
      cultures. Hypoxia (2%) induces hypoxia-inducible factor-1alpha (HIF-1alpha)
      activity followed by strong EPO expression in mixed cultures and weak expression
      in neuron-rich cultures as documented by both western blot and RT-PCR.
      Immunoreactive EPO was strongly detected in astrocytes, whereas EPOR was only
      detected in neurons. Neurons were significantly damaged in neuron-rich cultures
      but were distinctly rescued in mixed cultures. Application of recombinant human
      EPO (rhEPO) (0.1 U/mL) within 6 h before or after hypoxia significantly increased
      neuronal survival compared with no rhEPO treatment. Application of rhEPO after
      onset of reoxygenation achieved the maximal neuronal protection against
      ischemia/reperfusion injury (6 h hypoxia followed 24 h reoxygenation). Our
      results indicate that HIF-1alpha induces EPO gene released by astrocytes and acts
      as an essential mediator of neuroprotection, prove the protective role of
      intrinsic astrocytic-neuronal signaling pathway in hypoxic/ischemic injury and
      demonstrate an optimal therapeutic time-window of extrinsic rhEPO in
      ischemia/reperfusion injury in vitro. The results point to the potential
      beneficial effects of HIF-1alpha and EPO for the possible treatment of stroke.

PMID- 16417584
TI  - Cleavage of the membrane-bound transcription factor OASIS in response to
      endoplasmic reticulum stress.
AB  - When unfolded or misfolded proteins accumulate in the endoplasmic reticulum (ER),
      unfolded protein response (UPR) signals are transmitted from the ER to the
      nucleus and cytoplasm to facilitate protein folding. OASIS (old astrocyte
      specifically induced substance) is an ER stress transducer in astrocytes, a
      membrane-bound transcription factor that activates genes in the ER stress
      response. When unfolded proteins accumulate in the ER, OASIS is cleaved at the
      membrane to release its cytoplasmic domain, which then enters the nucleus and
      activates target genes. Here, we showed that OASIS is processed by Site-1 and -2
      proteases (S1P and S2P), enzymes that reside at the Golgi apparatus and process
      activating transcription factor 6 (ATF6), in response to ER stress. We also
      showed that the cleavage of OASIS is triggered by its translocation to the Golgi
      apparatus. All deletion mutants for luminal domain of OASIS showed that
      proteolytic processing and translocation to the Golgi apparatus remained intact,
      indicating that OASIS does not have significant sequences for Golgi localization
      signals, different from the case of ATF6, and that there could be other systems
      for translocation of OASIS to the Golgi apparatus in response to ER stress.

PMID- 16417587
TI  - Nitric oxide down-regulates caveolin-1 expression in rat brains during focal
      cerebral ischemia and reperfusion injury.
AB  - As a signalling molecule of the integral membrane protein family, caveolin
      participates in cellular signal transduction via interaction with other
      signalling molecules. The nature of interaction between nitric oxide (NO) and
      caveolin in the brain, however, remains largely unknown. In this study we
      investigated the role(s) of NO in regulating caveolin-1 expression in rat
      ischemic brains with middle cerebral artery occlusion (MCAO). Exposure to 1 h
      ischemia induced the increases in neuronal nitric oxide synthase (nNOS) and NO
      concentration with concurrent down-regulation of caveolin-1 expression in the
      ischemic core of rat brains. Subsequent 24 h or more reperfusion time led to an
      increase in inducible NOS (iNOS) expression and NO production, as well as a
      decline of caveolin-1 protein at the core and penumbra of the ischemic brain.
      Afterwards, NOS inhibitors and an NO donor were utilized to clarify the link
      between NO production and caveolin-1 expression in the rats with 1 h ischemia
      plus 24 h reperfusion. N(G)-nitro-l-arginine methyl ester (L-NAME, a non
      selective NOS inhibitor), N(6)-(1-iminoethyl)-lysine (NIL, an iNOS inhibitor),
      and 7-nitroindazole (7-NI, a nNOS inhibitor) prevented the loss of caveolin-1 in
      the core and penumbra of the ischemic brain, whereas l-N(5)-(1-iminoethyl)
      ornithine (L-NIO, an endothelial NOS inhibitor) showed less effect than the other
      NOS inhibitors. S-Nitroso-N-acetylpenicillamine (SNAP, a NO donor) down-regulated
      the expression of caveolin-1 protein in normal and ischemic brains. These
      results, when taken together, suggest that NO modulates the expression of
      caveolin-1 in the brain and that the loss of caveolin-1 is associated with NO
      production in the ischemic brain.

PMID- 16417588
TI  - Differential negative coupling of type 3 metabotropic glutamate receptor to
      cyclic GMP levels in neurons and astrocytes.
AB  - Metabotropic receptors may couple to different G proteins in different cells or
      perhaps even in different regions of the same cell. To date, direct studies of
      group II and group III metabotropic glutamate receptors' (mGluRs) relationships
      to second messenger cascades have reported negative coupling of these receptors
      to cyclic AMP (cAMP) levels in neurons, astrocytes and transfected cells. In the
      present study, we found that the peptide neurotransmitter N
      acetylaspartylglutamate (NAAG), an mGluR3-selective agonist, decreased sodium
      nitroprusside (SNP)-stimulated cyclic GMP (cGMP) levels in cerebellar granule
      cells and cerebellar astrocytes. The mGluR3 and group II agonists FN6 and
      LY354740 had similar effects on cGMP levels. The mGluR3 and group II antagonists
      beta-NAAG and LY341495 blocked these actions. Treatment with pertussis toxin
      inhibited the effects of NAAG on SNP-stimulated cGMP levels in rat cerebellar
      astrocytes but not in cerebellar neurons. These data support the conclusion that
      mGluR3 is also coupled to cGMP levels and that this mGluR3-induced reduction of
      cGMP levels is mediated by different G proteins in cerebellar astrocytes and
      neurons. We previously reported that this receptor is coupled to a cAMP cascade
      via a pertussis toxin-sensitive G protein in cerebellar neurons, astrocytes and
      transfected cells. Taken together with the present data, we propose that mGluR3
      is coupled to two different G proteins in granule cell neurons. These data
      greatly expand knowledge of the range of second messenger cascades induced by
      mGluR3, and have implications for clinical conditions affected by NAAG and other
      group II mGluR agonists.

PMID- 16417589
TI  - Activation of JAK/STAT signalling in neurons following spinal cord injury in
      mice.
AB  - The Janus kinase (JAK)/signal transducer and activator of transcription (STAT)
      signalling pathway is one of the most important in transducing signals from the
      cell surface to the nucleus in response to cytokines. In the present study, we
      investigated chronological alteration and cellular location of JAK1, STAT3,
      phosphorylated (p)-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and interleukin-6 (IL-6)
      following spinal cord injury (SCI) in mice. Western blot analysis showed JAK1 to
      be significantly phosphorylated at Tyr1022/1023 from 6 h after SCI, peaking at 12
      h and gradually decreasing thereafter, accompanied by phosphorylation of STAT3 at
      Tyr705 with a similar time course. ELISA analysis showed the concentration of IL
      6 in injured spinal cord to also significantly increase from 3 h after SCI,
      peaking at 12 h, then gradually decreasing. Immunohistochemistry revealed p
      Tyr1022/1023-JAK1, p-Tyr705-STAT3, and IL-6 to be mainly expressed in neurons of
      the anterior horns at 12 h after SCI. Pretreatment with a JAK inhibitor, AG-490,
      suppressed phosphorylation of JAK1 and STAT3 at 12 h after SCI, reducing recovery
      of motor functions. These findings suggest that SCI at the acute stage produces
      IL-6 mainly in neurons of the injured spinal cord, which activates the JAK/STAT
      pathway, and that this pathway may be involved with neuronal response to SCI.

PMID- 16417591
TI  - Pharmacology of botulinum toxin: differences between type A preparations.
AB  - Different types of botulinum neurotoxin (BoNT) block different proteins of the
      soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE)
      protein complex within cholinergic nerve terminals, producing blockade of
      cholinergic neuromuscular and autonomic synapses. Animal studies indicate the
      longest duration of action for BoNT type A (BoNTA) followed by types B, F, and E.
      Diffusion to adjacent and remote muscles may be related to protein composition,
      dilutions, volume, target muscle selection, and injection technique. A review of
      head-to-head, randomized, controlled trials of BoNTA preparations (Botox and
      Dysport) suggests that Dysport tends to have higher efficacy, longer duration,
      and higher frequency of adverse effects. Conversion factors between the
      preparations varied, however, and remain controversial. In clinical settings, a
      Botox:Dysport conversion ratio of 1:3 may be appropriate. Animal studies suggest
      a conversion ratio of 1:2.5-3. When therapeutic effects between these
      preparations are attempting to be equalized, Dysport seems to produce more
      adverse effects. In mice, Botox appears to have a better safety margin than
      Dysport and BoNTB. In rats, diffusion margins are similar for Botox and Dysport.
      Jitter derived from stimulation single-fiber EMG of injected and remote muscles
      show no differences between Botox and Dysport. Atrophy of extrafusal muscle
      fibers of injected and remote muscles do not differ between the BoNTA
      preparations.

PMID- 16417592
TI  - Immunological aspects of Botox, Dysport and Myobloc/NeuroBloc.
AB  - In some patients treated with botulinum toxin (BT), antibodies are produced in
      association with certain treatment parameters, patient characteristics and
      immunological properties of the BT preparation used. Therapeutic BT preparations
      are comprised of botulinum neurotoxin, non-toxic proteins and excipients.
      Antibodies formed against botulinum neurotoxin can block BT's biological
      activity. The antigenicity of a BT preparation depends on the amount of botulinum
      neurotoxin presented to the immune system. This amount is determined by the
      specific biological activity, the relationship between the biological activity
      and the amount of botulinum neurotoxin contained in the preparation. For Botox
      the specific biological activity is 60 MU-EV/ng neurotoxin, for Dysport 100 MU
      EV/ng neurotoxin and for Myobloc/NeuroBloc 5 MU-EV/ng neurotoxin. For
      Myobloc/NeuroBloc this translates into an antibody-induced therapy failure rate
      of 44% in patients treated for cervical dystonia, whereas for BT type A
      preparations this figure is approximately 5%. No obvious differences in
      antigenicity of BT type A preparations have been detected thus far. For the
      current formulation of Botox, the rate of antibody-induced therapy failure is
      reportedly less than 1%. To determine the antigenicity of different BT
      preparations in more detail, prospective studies on large series of unbiased
      patients with sensitive and specific BT antibody tests are necessary.

PMID- 16417593
TI  - Treatment of cervical dystonia with botulinum toxins.
AB  - Botulinum toxin (BoNT) treatment has been used extensively for the treatment of
      cervical dystonia. In most studies, there is significant improvement following
      treatment for head posture and pain. The common side effects following treatment
      include dysphagia, dry mouth, and neck weakness. There are five brands and two
      serotypes of BoNT available. The dosing of each serotype and brand differs.
      Perhaps more importantly, each brand and serotype may differ in immunogenic
      potential and occurrence of secondary unresponsiveness, an issue that is
      currently under active investigation. Although many aspects of the technique of
      injection have not been adequately studied, general guidelines are available.

PMID- 16417594
TI  - Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different
      botulinum toxin preparations.
AB  - Amongst all regions of the body, the craniocervical region is the one most
      frequently affected by dystonia. Whilst blepharospasm--involuntary bilateral eye
      closure--is produced by spasmodic contractions of the orbicularis oculi muscles,
      oromandibular dystonia may cause jaw closure with trismus and bruxism, or
      involuntary jaw opening or deviation, interfering with speaking and chewing. Both
      forms of dystonia can be effectively treated with botulinum toxin injection. This
      article summarizes injection techniques in both forms of dystonia and compares
      doses, potency and efficacy of different commercially available toxins, including
      Botox, Dysport, Xeomin and Myobloc/NeuroBloc.

PMID- 16417595
TI  - Botulinum toxin therapy of hemifacial spasm: comparing different therapeutic
      preparations.
AB  - Hemifacial spasm (HFS) is characterized by involuntary irregular clonic or tonic
      movements of the muscles innervated by cranial nerve VII on one side of the face,
      and is most often a result of vascular compression of the facial nerve at the
      root exit zone (Muscle and Nerve 1998;21:1740). Disability associated with this
      disorder ranges from social embarrassment to interference with vision resulting
      from involuntary eye closure. Treatment of HFS most often involves botulinum
      toxin injections, but may also include medications and surgery. We describe
      treatment with the three types of botulinum toxin currently commercially
      available--Botox, Dysport and Myobloc/NeuroBloc.

PMID- 16417596
TI  - Botulinum toxin therapy of laryngeal muscle hyperactivity syndromes: comparing
      different botulinum toxin preparations.
AB  - Spasmodic dysphonia (SD) is a focal dystonia characterized by a strained,
      strangled voice. Botulinum toxin is a symptomatic treatment for SD and has become
      the mainstay of therapy over the last two decades. In this manuscript, we briefly
      review different laryngeal muscle hyperactivity syndromes, their injection
      techniques and toxins currently available. Adductor SD is the most common
      indication for botulinum toxin treatment in the larynx. All studies report
      similar results with regard to improvement, patient satisfaction and side
      effects. We describe different injection techniques to treat this disorder such
      as the percutaneous, transoral, transnasal, point-touch techniques. In abductor
      SD, a subtype of SD, the treatment is aimed at the posterior cricoarytenoid
      muscle. Other applications of botulinum toxin in the larynx include spasmodic
      laryngeal dyspnea and voice tremors. We also review injection techniques, the
      different toxin types used, and toxin doses.

PMID- 16417597
TI  - Management of spasticity in adults: practical application of botulinum toxin.
AB  - Spasticity, characterized by increased muscle tone, exaggerated stretch reflexes,
      and abnormal limb posture, is a common sequel of central nervous system
      pathology. Historically, medicinal treatments have been of limited efficacy. This
      review discusses the clinical features of spasticity, the functional and
      pathological consequences, and treatment. It reviews the most common patterns of
      spasticity encountered in the upper and lower limbs and focuses on focal
      treatment of spastic muscles with the three commercially available botulinum
      toxins Botox, Dysport, and Myobloc/NeuroBloc. It addresses practical details such
      as muscle selection and identification, drug dilution, and doses.

PMID- 16417598
TI  - Botulinum toxin therapy of migraine and tension-type headache: comparing
      different botulinum toxin preparations.
AB  - Most of the initial reports on botulinum toxin in tension-type headache (TTH) and
      in migraine were positive. Unfortunately, these results were not reproduced in
      well-designed, randomized controlled trials. So far, doses from 20 U (Botox) to
      500 U (Dysport) have been studied in patients with chronic TTH, and doses from 16
      to 200 U (Botox) in patients with migraine. Overall, there is no evidence for a
      beneficial effect of botulinum toxin, although trends favoring botulinum toxin
      were reported. Experience with botulinum toxin type B (Myobloc/NeuroBloc) is
      limited and similar to the experience with the type A. Thus, a widespread use of
      botulinum toxin therapy in headache can currently not be recommended.

PMID- 16417599
TI  - Botulinum toxin therapy of writer's cramp.
AB  - The pathophysiology and management of writer's cramp is one of the most
      challenging amongst the various forms of focal dystonias. Frequently, the
      dystonic postures are confounded by compensatory muscle activity. Correct
      identification of target muscles for botulinum toxin (BT) injections determines
      the treatment success. The dosages of different preparations vary, with 1 unit of
      Botox roughly equalling 3.5 units of Dysport. Electromyographic guided injections
      yield better results and may also decrease the amount of toxin required. Weakness
      of target muscles interfering with other non-writing activities is a frequently
      encountered adverse effect. Studies have shown that BT is a safe long-term
      therapy option.

PMID- 16417600
TI  - Botulinum toxin treatment of sialorrhea: comparing different therapeutic
      preparations.
AB  - In recent years, a number of potential new therapeutic indications of botulinum
      toxin injections have emerged, amongst which sialorrhea has attracted
      considerable attention. Based on open-label and controlled studies, botulinum
      toxin can be used to improve sialorrhea in patients with Parkinson's disease,
      parkinsonian syndromes, motor neuron disease and cerebral palsy. The toxin can be
      injected blindly based on anatomic landmarks of the salivary glands, or
      localization can be facilitated by use of ultrasound guidance. There are few
      reported adverse effects. However, many more carefully designed, controlled
      studies are still required to address the specific questions related to selection
      of patients, the optimal injection technique, the appropriate dose of botulinum
      toxin and its long-term effects.

PMID- 16417601
TI  - Other indications of botulinum toxin therapy.
AB  - The therapeutic possibilities of botulinum toxin are manifold and certainly not
      yet fully exhausted. Apart from the classical indications--focal dystonia and
      focal spasticity--its use in the management of wrinkles has become well known.
      Moreover, the toxin is now being administered in many medical fields, including
      many other kinetic disorders like rare dystonias and tremor. The toxin is also
      used in a great number of autonomic disorders such as focal hyperhidrosis and
      even rhinitis. Substantial advances have been made in the field of urology after
      injections into the sphincter and detrusor muscle. Studies for approval are
      meanwhile under way concerning the treatment of detrusor hyperreflexia.
      Gastroenterology is another important field for application of botulinum toxin-
      be it to the esophagus (e.g. achalasia), stomach, gallbladder, or anorectum. Anal
      fissure is considered a particularly common indication. Controlled studies for
      many indications are frequently lacking because of the limited incidence of some
      of these disorders and symptoms.

PMID- 16417602
TI  - Peer review.

PMID- 16417603
TI  - Patellar luxation in 70 large breed dogs.
AB  - OBJECTIVES: To report the signalment, history, clinical features, and outcome in
      dogs weighing greater than 15 kg, treated surgically and non-surgically for
      patellar luxation. Risk factors for the development of patellar luxation,
      postoperative complications, and outcome were evaluated. METHODS: Details
      regarding signalment, bodyweight, breed, aetiology, unilateral or bilateral
      luxation, duration of lameness, grade of luxation, direction of luxation, grade
      of lameness at presentation, concomitant cranial cruciate ligament rupture,
      method of treatment, surgical technique, surgeon, and complications were obtained
      from the medical records. Outcome was graded as excellent, good, fair, or poor,
      according to the degree of lameness. RESULTS: Seventy dogs (45 males and 25
      females) were included. Thirty-five had bilateral luxations (105 limbs). Mean age
      was two years, and mean weight was 30 kg. The relative risk for Labrador
      retrievers was 3.3 (P<0.001). All luxations were developmental. Luxations were
      medial in 102 stifles and lateral in three. Fourteen stifles had concomitant
      cranial cruciate ligament rupture. As the grade of patellar luxation increased,
      so did the grade of lameness (P<0.001). Surgery was performed in 70 stifles, and
      outcome was excellent/good in 94 per cent and fair/poor in 6 per cent of stifles.
      Complications occurred in 29 per cent of stifles, and increasing bodyweight was
      found to be a risk factor (P=0.03). Thirty-five stifles were managed non
      surgically, and outcome was excellent/good in 86 per cent and fair/poor in 14 per
      cent of stifles. CLINICAL SIGNIFICANCE: In view of the potential risk of
      postoperative complications, all surgically treated cases of patellar luxation in
      large breed dogs should be managed with a femoral trochleoplasty, a tibial
      tuberosity transposition (stabilised with K-wires and a tension band wire), and
      soft tissue releasing and tightening procedures.

PMID- 16417604
TI  - Frequencies of blood type A, B and AB in non-pedigree domestic cats in Turkey.
AB  - OBJECTIVES: To determine the distribution of blood types and to estimate the
      proportion of matings at risk for neonatal isoerythrolysis in non-pedigree
      domestic cats. METHODS: The present survey determined the frequency of blood
      types in 301 cats from four distinct regions of Turkey.
      Ethylenediaminetetraacetic acid-anticoagulated blood samples were typed by simple
      tube and slide agglutination assays. Serum obtained from type B cats and an anti
      B solution, prepared with Triticum vulgaris, were used to determine type A and
      type B blood, respectively. RESULTS: Of the 301 cats typed, 220 had type A blood,
      74 had type B and seven had type AB. There was a significant difference (P<0.01)
      between the locations of the cats, with fewer type B cats in the eastern than in
      the western parts of Turkey. Risk for the development of neonatal isoerythrolysis
      due to A-B mismatch was estimated to be 18.6 per cent. CLINICAL SIGNIFICANCE: The
      overall type B frequency in Turkish domestic cats is high. Thus, untyped
      transfusions in these cats carry a high risk of life-threatening acute haemolytic
      transfusion reactions and neonatal isoerythrolysis. It is therefore strongly
      recommended that blood typing be performed before breeding or transfusing in
      order to minimise blood type incompatibility risks.

PMID- 16417605
TI  - The in vitro effects of piroxicam and meloxicam on canine cell lines.
AB  - OBJECTIVES: To analyse the direct antiproliferative effects of both piroxicam and
      meloxicam at a variety of concentrations on a series of canine cancer cell lines
      and the mechanism of cell death. METHODS: The in vitro effects of piroxicam and
      meloxicam at various concentrations on canine cell cultures (Madin-Darby canine
      kidney cells, osteosarcoma, mammary carcinoma, and lymphoma) were assessed with
      respect to proliferation inhibition and apoptosis induction. Western blot
      analysis of cyclooxygenase-1 and cyclooxygenase-2 expression was performed on all
      cell lines. RESULTS: All cell lines used in this study were cyclooxygenase-1 and
      cyclooxygenase-2 positive apart from Madin-Darby canine kidney cells which were
      negative for both cyclooxygenase-1 and cyclooxygenase-2. Both meloxicam and
      piroxicam were able to inhibit proliferation in cell lines in a dose-dependent
      manner. However, the drug concentration required for a given effect was cell line
      dependent. CLINICAL SIGNIFICANCE: The results suggest that significant inhibition
      of proliferation and induction of apoptosis would only occur when drug
      concentrations were in excess of those that can be achieved in vivo following
      maximum recommended dose rates. It is possible, however, that local or topical
      treatment or altered dosing regimens may offer alternative approaches to the use
      of these drugs as antineoplastic agents.

PMID- 16417607
TI  - Progressive dysphagia in a dog caused by a scirrhous, poorly differentiated
      perioesophageal carcinoma.
AB  - Investigation of canine dysphagia is performed by a combination of diagnostic
      imaging, direct visualisation of the upper gastrointestinal tract, and ancillary
      diagnostic testing to differentiate between structural and functional causes.
      Video fluoroscopy may be especially helpful. The case of a seven-year-old Border
      collie that presented with a history of progressive pharyngeal dysphagia is
      described. Fluoroscopic investigation was initially suggestive of functional
      pharyngeal disease, but magnetic resonance imaging and surgical exploration
      demonstrated the presence of a diffuse, scirrhous, poorly differentiated
      carcinoma with extensive oesophageal involvement. This case highlights that, in
      some circumstances, fluoroscopy may occasionally be of limited use in the
      investigation of dysphagia in the dog.

PMID- 16417606
TI  - Evaluation of colonoscopic allergen provocation as a diagnostic tool in dogs with
      proven food hypersensitivity reactions.
AB  - OBJECTIVE: To evaluate the colonoscopic allergen provocation (COLAP) test as a
      new tool for the diagnosis of IgE-mediated food allergy. METHODS: Oral food
      challenges as well as COLAP testing were performed in a colony of nine research
      dogs with proven immediate-type food allergic reactions. In addition, COLAP was
      performed in five healthy dogs. RESULTS: When compared with the oral challenge
      test, COLAP accurately determined 18 of 23 (73 per cent) positive oral challenge
      reactions (73 per cent) in dogs with food allergies and was negative in the
      healthy dogs. CLINICAL SIGNIFICANCE: The accuracy of this new test may be higher
      than that for gastric sensitivity testing. Therefore, COLAP holds promise as a
      new test to confirm the diagnosis of suspect IgE-mediated food allergy in dogs.

PMID- 16417608
TI  - Symmetrical double aortic arch in a beagle puppy.
AB  - Double aortic arch denotes the persistence of both fourth aortic arches and has
      been reported as 'very rare' in the dog. Most reported cases have been seen in
      German shepherd dogs. An eight-week-old, male, 1.5-kg beagle presented with a
      three-week history of regurgitation and dyspnoea. A barium oesophagram showed
      severe oesophageal constriction cranial to the base of the heart, and a
      provisional diagnosis of a persistent right aortic arch was made. A left-sided
      fourth intercostal thoracotomy was performed. The ligamentum arteriosum was
      ligated and divided. The oesophagus was seen lying on the right-hand side of the
      aorta. Postoperatively, the puppy deteriorated and was euthanized. Postmortem
      revealed a double aortic arch entrapping both the oesophagus and trachea. The
      inexperienced surgeon could consider computed tomography or angiography to
      determine the exact vascular ring, and other possible concurrent vascular
      anomalies present, before surgery.

PMID- 16417611
TI  - Candidate gene studies in the 21st century: meta-analysis, mediation, moderation.
AB  - The results of a large body of candidate gene studies of behavioural and
      psychiatric phenotypes have been largely inconclusive, with most findings failing
      to replicate reliably. A variety of approaches that augment the 'traditional'
      candidate gene approach are discussed, including the use of meta-analysis to
      combine findings from existing published reports, the investigation of mediating
      variables (including the use of intermediate phenotypes or endophenotypes) and
      the awareness of possible moderating influences (such as sex or ethnicity) and
      gene-environment interactions on genetic associations, possibly via epigenetic
      mechanisms. Advances in genotyping technology will also allow the routine use of
      haplotype analysis and linkage disequilibrium mapping. Examples of how these
      approaches may improve our understanding of how genetic associations with
      behavioural and psychiatric phenotypes obtain are given.

PMID- 16417609
TI  - Surgical removal of a canine orbital lipoma.
AB  - A 10-year-old, female, neutered Cairn terrier was presented with a progressively
      enlarging, cream-white fluctuant subconjunctival swelling in the right eye. A
      fine-needle aspirate performed under topical anaesthesia showed that the mass
      contained lipomatous tissue. Orbital ultrasonography showed the mass to have a
      distinct border and to extend into the posterior orbit. The mass was removed via
      a conjunctival incision. It had a distinct capsule anteriorly, while the border
      of the mass was less readily identified in the posterior orbit. Histopathological
      examination showed the mass to be a lipoma. The dog recovered uneventfully from
      surgery, and no recurrence has been noted after 12 months.

PMID- 16417612
TI  - Disputes over memory ownership: What memories are disputed?
AB  - The ownership of memories is sometimes disputed, particularly by twins.
      Examination of 77 disputed memories, 71 provided by twins, showed that most of
      the remembered events are negative and that the disputants appear to be self
      serving. They claim for themselves memories for achievements and suffered
      misfortunes but are more likely to give away memories of personal wrongdoing. The
      research suggests that some of the memories in which we play a leading role might
      in fact have been the experiences of others.

PMID- 16417613
TI  - Characterization of allelic variants at chromosome 15q14 in schizophrenia.
AB  - Evidence of genetic linkage for schizophrenia at chromosome 15q14 has been
      reported in nine independent studies, but the molecular variants responsible for
      transmission of genetic risk are unknown. National Institute of Mental Health
      Schizophrenia Genetics Initiative families were genotyped for single nucleotide
      polymorphisms (SNPs) and dinucleotide repeat markers in the 15q14 linkage region
      and analyzed based on the presence of particular alleles of the dinucleotide
      repeat marker D15S165 in the 15q14 region. Two alleles showed both familial
      transmission disequilibrium and population-wide association with schizophrenia.
      The two groups identified by these two D15S165 alleles differ in age of onset,
      number of hospitalizations and intensity of nicotine abuse, as well as in
      predominant ethnicity. Variations in the frequency of SNPs in CHRNA7, the alpha-7
      nicotinic acetylcholine receptor subunit gene at 15q14, were found in each group.
      Further sequencing in these two groups may yield more definitive identification
      of the molecular pathology.

PMID- 16417614
TI  - Influence and interactions of cathepsin D, HLA-DRB1 and APOE on cognitive
      abilities in an older non-demented population.
AB  - Cathepsin D (CTSD), human leukocyte antigen DRB1 (HLA-DRB1) and apolipoprotein E
      (APOE) have all been associated with cognitive ability in both demented and non
      demented individuals. CTSD is a pleiotrophic protein whose functions include the
      processing of proteins prior to presentation by HLA. Several studies have also
      reported that a functional exon 2 polymorphism in the CTSD gene interacts with
      APOEepsilon4 resulting in an increased risk of developing Alzheimer's disease
      (AD). We have previously reported that the CTSD exon 2 polymorphism regulates
      fluid intelligence. In this study, we extend this finding to other cognitive
      domains and investigate interactions with APOE and HLA-DRB1. Using a cohort of
      766 non-demented volunteers, we found that the CTSD exon 2 T allele was
      associated with a decrease in several cognitive domains that comprise processing
      speed [random letters (RLs) test, P = 0.012; alphabet-coding task (ACT), P =
      0.001], spatial recall (SR) (P = 0.016) and an additional test of fluid
      intelligence (P = 0.010). We also observed that the HLA-DR1 was associated with
      enhanced cumulative recall ability (P = 0.006), and conversely HLA-DR5 was
      associated with diminished delayed verbal recall and SR abilities (P = 0.014 and
      P = 0.003, respectively). When analysed independently, APOEepsilon4 did not
      influence any cognitive domains. In contrast, CTSD T/APOEepsilon4-positive
      volunteers scored lower on tests of fluid intelligence (P = 0.015), processing
      speed (ACT, P = 0.001; RL, P = 0.013) and immediate recall (P = 0.029). Scores
      were lower for all these tests than when CTSD and APOE were analysed
      independently. This supports previous findings in AD that have also reported an
      epistatic interaction. In addition, we found that CTSD T/HLA-DR2-positive
      volunteers had reduced processing speed (ACT, P = 0.040; RL, P = 0.014) and had
      significantly lower cumulative and SR abilities (P = 0.003 and P = 0.001,
      respectively). Biological interaction between these two proteins has previously
      been shown where HLA-DR2 binds more readily to the myelin basic protein (MBP)
      compared with other DR antigens, preventing MBP cleavage by CTSD.

PMID- 16417615
TI  - Quantitative trait loci for IQ and other complex traits: single-nucleotide
      polymorphism genotyping using pooled DNA and microarrays.
AB  - Similar to other complex traits, it is likely that many DNA polymorphisms of
      small effect size [quantitative trait loci (QTLs)] are responsible for the high
      heritability of intelligence, in addition to many rare monogenic disorders known
      to contribute to lowered intelligence. We review the current status of approaches
      to identify QTLs associations for intelligence employing genome-wide strategies
      using pooled DNA from many individuals and evaluate the innovative approach of
      microarray analysis to genotype DNA pools for large numbers of single nucleotide
      polymorphisms.

PMID- 16417616
TI  - Gene expression profiling of primate neocortex: molecular neuroanatomy of
      cortical areas.
AB  - One hundred years have passed since Brodmann's mapping of the mammalian
      neocortex. Solely on the basis of morphological observations, he envisaged the
      conservation and differentiation of cortical areal structures across various
      species. We now know that neurochemical, connectional and functional
      heterogeneity of the neocortex accompanies the morphological divergence observed
      in such cytoarchitectonic studies. Nevertheless, we are yet far from fully
      understanding the biological significance of this cortical heterogeneity. In this
      article, we review our past works on the gene expression profiling of the
      postnatal primate cortical areas, by quantitative real-time polymerase chain
      reaction (PCR), DNA array, differential display PCR and in situ hybridization
      analyses. These studies revealed both the overall homogeneity of gene expression
      across different cortical areas and the presence of a small number of genes that
      show markedly area-specific expression patterns. In situ hybridization showed
      that, among such genes, occ1 and retinol-binding protein (RBP) mRNAs are
      selectively expressed in the neuronal populations that seem to be involved in
      distinct neural processing such as sensory reception (for occ1) and associative
      function (for RBP). Such a molecular neuroanatomical approach has the promise to
      provide an important link between structure and function of the cerebral cortex.

PMID- 16417617
TI  - Investigating cognitive genetics and its implications for the treatment of
      cognitive deficit.
AB  - Cognitive impairment in the elderly, caused by either normal ageing process or
      dementia, is an increasing problem in developed countries that has enormous
      social and economic considerations. Research investigating the genetic basis of
      cognition is a new and rapidly developing field that may aid in the development
      of new treatments for age-related cognitive deficit. Over the past 6 years, a
      number of quantitative trait loci (QTLs) have been associated with cognitive
      functioning in humans including loci within the genes catechol-o
      methyltransferase, brain-derived neurotrophic factor, muscle segment homeobox 1,
      serotonin transporter 2A (HTR2A), cholinergic muscarinic receptor 2, cathepsin D,
      metabotrophic glutamate receptor and most recently the class II human leukocyte
      antigens. Unfortunately, inconsistency within the literature, which is a hallmark
      of almost all association studies investigating complex diseases and traits, is
      casting doubt as to which genes are truly associated with cognition and which are
      a result of Type 2 error. This review will highlight implicated intelligence
      QTLs, examine the probable reasons for the current discrepancies between reports
      and discuss the potential advantages that may be procured from the study of
      cognitive genetics.

PMID- 16417618
TI  - Deconstructing language by comparative gene expression: from neurobiology to
      microarray.
AB  - Language is a defining characteristic of our species that has emerged quite
      recently on an evolutionary timescale. Understanding the neurobiological
      substrates and genetic underpinnings of language constitutes a basic challenge
      for both neuroscience and genetics. The functional localization of language in
      the brain has been progressively refined over the last century through studies of
      aphasics and more recently through neuroimaging. Concurrently, structural
      specializations in these brain regions have been identified by virtue of their
      lateralization in humans and also through comparisons with homologous brain
      regions in non-human primate species. Comparative genomics has revealed the
      genome of our closest living relative, the chimpanzee, to be astonishingly
      similar to our own. To explore the role that changes in the regulation of gene
      expression have had in recent human evolution, several groups have used
      microarrays to compare expression levels for thousands of genes in the brain
      between humans and chimpanzees. By applying this approach to the increasingly
      refined peri-sylvian network of brain regions involved in language, it may be
      possible to discern functionally significant changes in gene expression that are
      universal among humans but unique to our species, thus casting light on the
      molecular basis of language in the brain.

PMID- 16417620
TI  - Comparative gene expression in brain regions of human alcoholics.
AB  - The mesocorticolimbic system is the reward centre of the brain and the major
      target for drugs of abuse including alcohol. Neuroadaptive changes in this region
      are thought to underlie the process of tolerance and dependence. Recently,
      several research groups have searched for alcohol-responsive genes using high
      throughput microarrays and well-characterized human post-mortem material.
      Comparison of data from these studies of cortical regions highlights the
      differences in experimental approach and selection of cases. However, alcohol
      responsive gene sets associated with transcription, oxidative stress and energy
      production were common to these studies. In marked contrast, alcohol-responsive
      genes in the nucleus accumbens and the ventral tegmental area are primarily
      associated with changes in neurotransmission and signal transduction. These data
      support the concept that, within cortical regions, changes in gene expression are
      associated with alcoholism-related pathology. In the dopaminergic tract of the
      mesocorticolimbic system, alcohol-responsive gene sets suggest long-term
      neuroplastic changes in synaptic transmission.

PMID- 16417621
TI  - European active surveillance study of women taking HRT (EURAS-HRT): study
      protocol [NCT00214903].
AB  - BACKGROUND: The post marketing safety surveillance program for a drug containing
      a new chemical entity should assess both, the safety outcomes that relate
      specifically to the targeted population, as well as those that could potentially
      be related to special pharmacological characteristics of the drug. Active safety
      surveillance using valid epidemiological study designs has been proven to be a
      pertinent and reliable method to approach this endeavor. METHODS/DESIGN: The
      primary objective of the study is to compare incidence rates of serious adverse
      events in users of all types of newly prescribed oral HRT products. This active
      surveillance study will assess pertinent cardiovascular outcomes--in particular
      venous and arterial thromboembolism--and other serious adverse events (SAEs) in
      new HRT users over a period of several years. One product under surveillance is
      Angeliq, which contains the novel progestagen drospirenone (DRSP) combined with
      estradiol. In addition, all other oral combined HRT products with a novel
      progestagen or estrogen that will be newly marketed during the study period will
      be studied. These new HRT products will be compared with established HRT
      products. The combined cohort will include at least 30,000 women recruited in
      several European countries. At least 90,000 years of observation are expected
      from the field work which started in early 2002 and will end around 2008. The
      participating women will complete a baseline survey using a self-administered
      questionnaire to describe the baseline risk. After 6 months, 12 months, and then
      on an annual basis, they will fill out a questionnaire in which they record
      complaints and events during the use of the prescribed HRTs. All adverse outcomes
      occurring during the observational period will be evaluated. DISCUSSION: A
      complete lifetime medical history, individually validated SAEs over time, and a
      low loss to follow-up rate are essential for a robust safety assessment.
      Therefore, the lifetime history of diseases and relevant medications will be
      documented. Reported SAEs will be validated and analyzed. A four level, multi
      faceted follow-up process was established to ensure low loss to follow-up rates
      (e.g., 3-5% after three years of follow up). Multivariate methods will be used to
      adjust for confounding.

PMID- 16417619
TI  - Exploiting human anatomical variability as a link between genome and cognome.
AB  - Although talents and disabilities appear to run in families, direct links between
      genes and cognitive ability are difficult to establish. Investigators are
      currently searching for intermediate phenotypes with plausible links to both
      genome and cognome (the cognitive phenotype). Cortical anatomy could provide one
      such intermediate phenotype. Variation in cortical size, asymmetry and sulcal
      pattern is influenced by genetic variation in neurotrophic factors and can
      predict variation in verbal and mathematical talent. Anecdotal evidence suggests
      that individuals with a rare morphological variant of Sylvian fissure sometimes
      have superior visualization ability combined with verbal deficits. Documentation
      of such 'cognitive cortical syndromes' might prove as genetically informative as
      the identification of dysmorphic syndromes associated with mental retardation. A
      necessary prerequisite for the establishment of such syndromes is a reliable
      technique for the identification of cortical patterns. Recent technical advances
      in software for automatically labeling and measuring cortical sulci now provide
      the possibility of establishing standard measures for their shape, size and
      location. Such measures are a prerequisite for genetic studies of cortical
      patterns that could illuminate the neurodevelopmental pathways by which genes
      affect cognitive ability.

PMID- 16417623
TI  - Dose-response characteristics of methylphenidate on locomotor behavior and on
      sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving
      rats.
AB  - BACKGROUND: Methylphenidate (MPD) is a psychostimulant commonly prescribed for
      attention deficit/hyperactivity disorder. The mode of action of the brain
      circuitry responsible for initiating the animals' behavior in response to
      psychostimulants is not well understood. There is some evidence that
      psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens
      (NAc), and prefrontal cortex (PFC). METHODS: The present study was designed to
      investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on
      locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and
      PFC in freely behaving rats previously implanted with permanent electrodes. For
      locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline
      on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5,
      or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2
      h post injection on both days using an automated, computerized activity
      monitoring system. Electrophysiological recordings were also performed in the
      adult male WKY rats (n = 10). Five to seven days after the rats had recovered
      from the implantation of electrodes, each rat was placed in a sound-insulated,
      electrophysiological test chamber where its sensory evoked field potentials were
      recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time
      interval between injections was 90 min. RESULTS: Results showed an increase in
      locomotion with dose-response characteristics, while a dose-response decrease in
      amplitude of the components of sensory evoked field responses of the VTA, NAc,
      and PFC neurons. For example, the P3 component of the sensory evoked field
      response of the VTA decreased by 19.8% +/- 7.4% from baseline after treatment of
      0.6 mg/kg MPD, 37.8% +/- 5.9% after 2.5 mg/kg MPD, and 56.5% +/- 3.9% after 10
      mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC.
      Differences in the intensity of MPD-induced attenuation were also found among
      these brain areas. CONCLUSION: These results suggest that an acute treatment of
      MPD produces electrophysiologically detectable alterations at the neuronal level,
      as well as observable, behavioral responses. The present study is the first to
      investigate the acute dose-response effects of MPD on behavior in terms of
      locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and
      PFC neurons in intact, non-anesthetized, freely behaving rats previously
      implanted with permanent electrodes.

PMID- 16417622
TI  - Evaluation of methods for oligonucleotide array data via quantitative real-time
      PCR.
AB  - BACKGROUND: There are currently many different methods for processing and
      summarizing probe-level data from Affymetrix oligonucleotide arrays. It is of
      great interest to validate these methods and identify those that are most
      effective. There is no single best way to do this validation, and a variety of
      approaches is needed. Moreover, gene expression data are collected to answer a
      variety of scientific questions, and the same method may not be best for all
      questions. Only a handful of validation studies have been done so far, most of
      which rely on spike-in datasets and focus on the question of detecting
      differential expression. Here we seek methods that excel at estimating relative
      expression. We evaluate methods by identifying those that give the strongest
      linear association between expression measurements by array and the "gold
      standard" assay. Quantitative reverse-transcription polymerase chain reaction
      (qRT-PCR) is generally considered the "gold-standard" assay for measuring gene
      expression by biologists and is often used to confirm findings from microarray
      data. Here we use qRT-PCR measurements to validate methods for the components of
      processing oligo array data: background adjustment, normalization, mismatch
      adjustment, and probeset summary. An advantage of our approach over spike-in
      studies is that methods are validated on a real dataset that was collected to
      address a scientific question. RESULTS: We initially identify three of six
      popular methods that consistently produced the best agreement between oligo array
      and RT-PCR data for medium- and high-intensity genes. The three methods are
      generally known as MAS5, gcRMA, and the dChip mismatch mode. For medium- and high
      intensity genes, we identified use of data from mismatch probes (as in MAS5 and
      dChip mismatch) and a sequence-based method of background adjustment (as in
      gcRMA) as the most important factors in methods' performances. However, we found
      poor reliability for methods using mismatch probes for low-intensity genes, which
      is in agreement with previous studies. CONCLUSION: We advocate use of sequence
      based background adjustment in lieu of mismatch adjustment to achieve the best
      results across the intensity spectrum. No method of normalization or probeset
      summary showed any consistent advantages.

PMID- 16417624
TI  - Departure from multiplicative interaction for catechol-O-methyltransferase
      genotype and active/passive exposure to tobacco smoke among women with breast
      cancer.
AB  - BACKGROUND: Women with homozygous polymorphic alleles of catechol-O
      methyltransferase (COMT-LL) metabolize 2-hydroxylated estradiol, a suspected
      anticarcinogenic metabolite of estrogen, at a four-fold lower rate than women
      with no polymorphic alleles (COMT-HH) or heterozygous women (COMT-HL). We
      hypothesized that COMT-LL women exposed actively or passively to tobacco smoke
      would have higher exposure to 2-hydroxylated estradiol than never-active/never
      passive exposed women, and should therefore have a lower risk of breast cancer
      than women exposed to tobacco smoke or with higher COMT activity. METHODS: We
      used a case-only design to evaluate departure from multiplicative interaction
      between COMT genotype and smoking status. We identified 502 cases of invasive
      incident breast cancer and characterized COMT genotype. Information on tobacco
      use and other potential breast cancer risk factors were obtained by structured
      interviews. RESULTS: We observed moderate departure from multiplicative
      interaction for COMT-HL genotype and history of ever-active smoking (adjusted
      odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 0.7, 3.8) and more
      pronounced departure for women who smoked 40 or more years (aOR = 2.3, 95% CI:
      0.8, 7.0). We observed considerable departure from multiplicative interaction for
      COMT-HL genotype and history of ever-passive smoking (aOR = 2.0, 95% CI: 0.8,
      5.2) or for having lived with a smoker after age 20 (aOR = 2.8, 95% CI: 0.8, 10).
      CONCLUSION: With greater control over potential misclassification errors and a
      large case-only population, we found evidence to support an interaction between
      COMT genotype and tobacco smoke exposure in breast cancer etiology.

PMID- 16417625
TI  - HIV/AIDS mitigation strategies and the State in sub-Saharan Africa--the missing
      link?
AB  - BACKGROUND: The HIV/AIDS pandemic in sub-Saharan Africa is widely recognised as a
      development disaster threatening poverty reduction, economic growth and not
      merely a health issue. Its mitigation includes the societal-wide adoption and
      implementation of specific health technologies, many of which depend on
      functional institutions and State. DISCUSSION: Donor and International
      Institutions' strategies to mitigate HIV/AIDS in sub-Saharan Africa are premised
      on a single optimal model of the State, one which focuses on the decentralised
      delivery of public goods alone (such as healthcare) - the service delivery state.
      The empirical evidence, though sparse, of "successful" and "unsuccessful" sub
      Saharan Africa states' performance in mitigating HIV/AIDS does not support this
      model. Rather, the evidence suggests an alternative model that takes a country
      context specific approach - encompassing political power, institutional
      structures and the level of health technology needed. This model draws on the
      historical experience of East Asian countries' rapid development. SUMMARY: For
      international public health policies to be effective, they must consider a
      country tailored approach, one that advocates a coordinated strategy designed and
      led by the State with involvement of wider society specific to each country's
      particular history, culture, and level of development.

PMID- 16417626
TI  - Defining localities of inadequate treatment for childhood asthma: a GIS approach.
AB  - BACKGROUND: The use of Geographic Information Systems (GIS) has great potential
      for the management of chronic disease and the analysis of clinical and
      administrative health care data. Asthma is a chronic disease associated with
      substantial morbidity, mortality, and health care use. Epidemiologic data from
      all over the world show an increasing prevalence of asthma morbidity and
      mortality despite the availability of effective treatment. These facts led to the
      emergence of strategies developed to improve the quality of asthma care. THE
      OBJECTIVE: To develop an efficient tool for quality assurance and chronic disease
      management using a Geographic Information System (GIS). GEOGRAPHIC LOCATION: The
      southern region of Israel. January 1998 - October 2000. DATABASES: Administrative
      claims data of the largest HMO in Israel: drug dispensing registry, demographic
      data, Emergency Room visits, and hospitalization data bases. METHODS: We created
      a list of six markers for inadequate pharmaceutical treatment of childhood asthma
      from the Israeli clinical guidelines. We used this list to search the drug
      dispensing registry to identify asthmatic children who received inadequate
      treatment and to assess their health care utilization and bad outcomes: emergency
      room visits and hospitalizations. Using GIS we created thematic maps on which we
      located the clinics with a high percentage of children for whom the treatment
      provided was not in adherence with the clinical guidelines. RESULTS: 81% of the
      children were found to have at least one marker for inadequate treatment; 17.5%
      were found to have more than one marker. Children with markers were found to have
      statistically significant higher rates of Emergency Room visits, hospitalizations
      and longer length of stay in hospital compared with children without markers. The
      maps show in a robust way which clinics provided treatment not in accord with the
      clinical guidelines. Those clinics have high rates of Emergency Room visits,
      hospitalizations and length of stay. CONCLUSION: Integration of clinical
      guidelines, administrative data and GIS can create an efficient interface between
      administrative and clinical information. This tool can be used for allocating
      sites for quality assurance interventions.

PMID- 16417628
TI  - The relationship between obesity, hyperglycemia symptoms, and health-related
      quality of life among Hispanic and non-Hispanic white children and adolescents.
AB  - BACKGROUND: The current study was conducted to evaluate the effects of
      overweight, hyperglycemia symptoms, Hispanic ethnicity, and language barriers on
      health-related quality of life (HRQoL) among children and adolescents. METHODS:
      Parents'/guardians of a population based sample of 5530 children between ages 3
      and 18 were administered the parents' version of the KINDL survey instrument to
      assess HRQoL in children and adolescents. Multiple linear regression analysis was
      used to assess relationships between HRQoL, body mass index, and hyperglycemia
      symptoms categories. RESULTS: The mean age of children was 10.6 (SD = 4.3). The
      mean KINDL total score was 79.7 (SD = 11.6) and the mean physical functioning
      score was 81.9 (SD = 20.3). Male children exhibited better physical health as
      compared to the female children (p < 0.001). Overweight children had lower
      overall HRQoL (p = 0.008). However, the association was not significant for the
      four of the six subscales including the physical health domain. Children with
      hyperglycemia symptoms and a family history of diabetes also had significantly
      lower overall and physical health HRQoL (p < 0.05). Children diagnosed with
      diabetes and in lower income strata also had significantly lower overall HRQoL (p
      < 0.05). No significant association between the Hispanic ethnicity and HRQoL was
      observed. However, those who reported mostly speaking Spanish exhibited
      significantly lower overall HRQoL (p = 0.001). CONCLUSION: Results suggest that
      overweight may reduce overall quality of life among children, though it does not
      directly influence physical functioning. However, hyperglycemia symptoms may
      affect both overall health and physical functioning. Findings also suggest the
      need for developing programs directed at overcoming language barriers that may
      face Spanish-speaking children or their parents. Furthermore, targeting children
      who have hyperglycemia symptoms with public information campaigns may be more
      appropriate than targeting overweight children.

PMID- 16417627
TI  - Does tumorigenesis select for or against mutations of the DNA repair-associated
      genes BRCA2 and MRE11?: considerations from somatic mutations in microsatellite
      unstable (MSI) gastrointestinal cancers.
AB  - BACKGROUND: The BRCA2 and MRE11 proteins participate in the repair of double
      strand DNA breaks by homologous recombination. Germline BRCA2 mutations
      predispose to ovarian, breast and pancreatic cancer, while a germline MRE11
      mutation is associated with an ataxia telangiectasia-like disorder. Somatic
      mutations of BRCA2 are rare in typical sporadic cancers. In tumors having
      microsatellite instability (MSI), somatic truncating mutations in a poly [A]
      tract of BRCA2 are reported on occasion. RESULTS: We analyzed gastrointestinal
      MSI cancers by whole gene BRCA2 sequencing, finding heterozygous truncating
      mutations in seven (47%) of 15 patients. There was no cellular functional defect
      in RAD51 focus-formation in three heterozygously mutated lines studied, although
      other potential functions of the BRCA2 protein could still be affected. A prior
      report of mutations in primary MSI tumors affecting the IVS5-(5-15) poly [T]
      tract of the MRE11 gene was confirmed and extended by analysis of the genomic
      sequence and protein expression in MSI cancer cell lines. Statistical analysis of
      the published MRE11 mutation rate in MSI tumors did not provide evidence for a
      selective pressure favoring biallelic mutations at this repeat. CONCLUSION:
      Perhaps conflicting with common suspicions, the data are not compatible with
      selective pressures during tumorigenesis promoting the functional loss of BRCA2
      and MRE11 in MSI tumors. Instead, these data fit closely with an absence of
      selective pressures acting on BRCA2 and MRE11 gene status during tumorigenesis.

PMID- 16417629
TI  - Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and
      apoptosis in human colon cancer cell lines.
AB  - BACKGROUND: Mediterranean societies, with diets rich in vitamin E isoforms, have
      a lower risk for colon cancer than those of northern Europe and the Americas.
      Vitamin E rich diets may neutralize free radicals generated by fecal bacteria in
      the gut and prevent DNA damage, but signal transduction activities can occur
      independent of the antioxidant function. The term vitamin E represents eight
      structurally related compounds, each differing in their potency and mechanisms of
      chemoprevention. The RRR-gamma-tocopherol isoform is found primarily in the US
      diet, while RRR-alpha-tocopherol is highest in the plasma. METHODS: The
      effectiveness of RRR-alpha- and RRR-gamma-tocopherol at inhibiting cell growth
      and inducing apoptosis in colon cancer cell lines with varying molecular
      characteristics (SW480, HCT-15, HCT-116 and HT-29) and primary colon cells (CCD
      112CoN, nontransformed normal phenotype) was studied. Colon cells were treated
      with and without RRR-alpha- or RRR-gamma-tocopherol using varying tocopherol
      concentrations and time intervals. Cell proliferation and apoptosis were measured
      using the trypan blue assay, annexin V staining, DNA laddering and caspase
      activation. RESULTS: Treatment with RRR-gamma-tocopherol resulted in significant
      cell death for all cancer cell lines tested, while RRR-alpha-tocopherol did not.
      Further, RRR-gamma-tocopherol treatment showed no cytotoxicity to normal colon
      cells CCD-112CoN at the highest concentration and time point tested. RRR-gamma
      tocopherol treatment resulted in cleavage of PARP, caspase 3, 7, and 8, but not
      caspase 9. Differences in the percentage cell death and apoptosis were observed
      in different cell lines suggesting that molecular differences in these cell lines
      may influence the ability of RRR-gamma-tocopherol to induce cell death.
      CONCLUSION: This is the first study to demonstrate that multiple colon cancer
      cell lines containing varying genetic alterations will under go growth reduction
      and apoptosis in the presence of RRR-gamma-tocopherol without damage to normal
      colon cells. The amount growth reduction was dependent upon the molecular
      signatures of the cell lines. Since RRR-gamma-tocopherol is effective at
      inhibition of cell proliferation at both physiological and pharmacological
      concentrations dietary RRR-gamma-tocopherol may be chemopreventive, while
      pharmacological concentrations of RRR-gamma-tocopherol may aid chemotherapy
      without toxic effects to normal cells demonstrated by most chemotherapeutic
      agents.

PMID- 16417631
TI  - Single dose targeted intraoperative radiotherapy (TARGIT) for breast cancer can
      be delivered as a second procedure under local anaesthetic.
AB  - BACKGROUND: Intraoperative radiotherapy (IORT) is promising approach that is
      being tested in randomised clinical trials. In the Targit (TARGeted
      Intraopeartive radioTherapy) trial IORT can be delivered at the time of primary
      surgery or as a second procedure. Patients prefer the single procedure of
      intraoperative radiotherapy even if it is under general anaesthetic to 6-weeks of
      daily visits for conventional external beam radiotherapy. CASE PRESENTATION: We
      report a case of a 70 year lady who underwent lumpectomy and axillary sampling
      and in whom we successfully administered IORT under local anaesthetic.
      CONCLUSION: In selected patients, this attractive option may make the procedure
      even more widely applicable.

PMID- 16417630
TI  - Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after
      TNBS induced colitis in rats.
AB  - BACKGROUND: N-methyl-D-aspartic acid (NMDA) spinal cord receptors play an
      important role in the development of hyperalgesia following inflammation. It is
      unclear, however, if changes in NMDA subunit receptor gene expression in the
      colonic myenteric plexus are associated with colonic inflammation. We
      investigated regulation of NMDA-NR1 receptor gene expression in TNBS induced
      colitis in rats. Male Sprague-Dawley rats (150 g-250 g) were treated with 20 mg
      trinitrobenzene sulfonic acid (TNBS) diluted in 50% ethanol. The agents were
      delivered with a 24 gauge catheter inserted into the lumen of the colon. The
      animals were sacrificed at 2, 7, 14, 21, and 28 days after induction of the
      colitis, their descending colon was retrieved for reverse transcription
      polymerase chain reaction; a subset of animals' distal colon was used for two
      dimensional (2-D) western analysis and immunocytochemistry. RESULTS: NR1-exon 5
      (N1) and NR1-exon 21 (C1) appeared 14, 21 and 28 days after TNBS treatment. NR1
      pan mRNA was up-regulated at 14, 21, and 28 days. The NR1-exon 22 (C2) mRNA did
      not show significant changes. Using 2-D western analysis, untreated control rats
      were found to express only NR1001 whereas TNBS treated rats expressed NR1001,
      NR1011, and NR1111. Immunocytochemistry demonstrated NR1-N1 and NR1-C1 to be
      present in the myenteric plexus of TNBS treated rats. CONCLUSION: These results
      suggest a role for colonic myenteric plexus NMDA receptors in the development of
      neuronal plasticity and visceral hypersensitivity in the colon. Up-regulation of
      NMDA receptor subunits may reflect part of the basis for chronic visceral
      hypersensitivity in conditions such as post-infectious irritable bowel syndrome.

PMID- 16417632
TI  - HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes
      heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1.
AB  - BACKGROUND: Heparin/heparan sulfate (HS) proteoglycans are found in the
      extracellular matrix (ECM) and on the cell surface. A considerable body of
      evidence has established that heparin and heparan sulfate proteoglycans (HSPGs)
      interact with numerous protein ligands including fibroblast growth factors,
      vascular endothelial growth factor (VEGF), cytokines, and chemokines. These
      interactions are highly dependent upon the pattern of sulfation modifications
      within the glycosaminoglycan chains. We previously cloned a cDNA encoding a novel
      human endosulfatase, HSulf-2, which removes 6-O-sulfate groups on glucosamine
      from subregions of intact heparin. Here, we have employed both recombinant HSulf
      2 and the native enzyme from conditioned medium of the MCF-7-breast carcinoma
      cell line. To determine whether HSulf-2 modulates the interactions between
      heparin-binding factors and heparin, we developed an ELISA, in which soluble
      factors were allowed to bind to immobilized heparin. RESULTS: Our results show
      that the binding of VEGF, FGF-1, and certain chemokines (SDF-1 and SLC) to
      immobilized heparin was abolished or greatly diminished by pre-treating the
      heparin with HSulf-2. Furthermore, HSulf-2 released these soluble proteins from
      their association with heparin. Native Sulf-2 from MCF-7 cells reproduced all of
      these activities. CONCLUSION: Our results validate Sulf-2 as a new tool for
      deciphering the sulfation requirements in the interaction of protein ligands with
      heparin/HSPGs and expand the range of potential biological activities of this
      enzyme.

PMID- 16417635
TI  - Saline Systems highlights for 2005.
AB  - On the 4th of July, 2005, the Saline Systems editorial group launched the new
      online open access journal, Saline Systems, with BioMed Central as the publisher.
      The scope of the journal includes both basic and applied research on halophilic
      organisms and saline environments, from gene systems to ecosystems. The stated
      goal of the journal is to meet publication needs for researchers working in
      coastal and inland saline environments and provide an interdisciplinary and
      readily accessible forum for scientists worldwide. The inaugural volume of the
      journal contains a significant number of high quality original research papers
      and reviews on a wide range of relevant topics. At the end of the launch period,
      from January 1, 2006 onwards, the journal will be introducing article-processing
      charges to cover the cost of publication. Charges will be partly or completely
      waived for authors from BioMed Central institutional subscribers and in cases of
      financial hardship.

PMID- 16417633
TI  - Administration of zoledronic acid enhances the effects of docetaxel on growth of
      prostate cancer in the bone environment.
AB  - BACKGROUND: After development of hormone-refractory metastatic disease, prostate
      cancer is incurable. The recent history of chemotherapy has shown that with
      difficult disease targets, combinatorial therapy frequently offers the best
      chance of a cure. In this study we have examined the effects of a combination of
      zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP
      23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when
      grown in the bone environment. METHODS: Intra-tibial injections of LuCaP 23.1
      cells were used to generate tumors in the bone environment, and animals were
      treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor
      were evaluated by measurements of bone mineral density and histomorphometrical
      analysis. RESULTS: ZOL decreased proliferation of LuCaP 23.1 in the bone
      environment, while docetaxel at a dose that effectively inhibited growth of
      subcutaneous tumors did not show any effects in the bone environment. The
      combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors
      in the bone. CONCLUSION: In conclusion, the use of the osteolysis-inhibitory
      agent ZOL in combination with docetaxel inhibits growth of prostate tumors in
      bone and represents a potential treatment option.

PMID- 16417636
TI  - GenoLink: a graph-based querying and browsing system for investigating the
      function of genes and proteins.
AB  - BACKGROUND: A large variety of biological data can be represented by graphs.
      These graphs can be constructed from heterogeneous data coming from genomic and
      post-genomic technologies, but there is still need for tools aiming at exploring
      and analysing such graphs. This paper describes GenoLink, a software platform for
      the graphical querying and exploration of graphs. RESULTS: GenoLink provides a
      generic framework for representing and querying data graphs. This framework
      provides a graph data structure, a graph query engine, allowing to retrieve sub
      graphs from the entire data graph, and several graphical interfaces to express
      such queries and to further explore their results. A query consists in a graph
      pattern with constraints attached to the vertices and edges. A query result is
      the set of all sub-graphs of the entire data graph that are isomorphic to the
      pattern and satisfy the constraints. The graph data structure does not rely upon
      any particular data model but can dynamically accommodate for any user-supplied
      data model. However, for genomic and post-genomic applications, we provide a
      default data model and several parsers for the most popular data sources.
      GenoLink does not require any programming skill since all operations on graphs
      and the analysis of the results can be carried out graphically through several
      dedicated graphical interfaces. CONCLUSION: GenoLink is a generic and interactive
      tool allowing biologists to graphically explore various sources of information.
      GenoLink is distributed either as a standalone application or as a component of
      the Genostar/Iogma platform. Both distributions are free for academic research
      and teaching purposes and can be requested at academy@genostar.com. A commercial
      licence form can be obtained for profit company at info@genostar.com. See also
      http://www.genostar.org.

PMID- 16417637
TI  - An extensible spatial and temporal epidemiological modelling system.
AB  - BACKGROUND: This paper describes the Spatiotemporal Epidemiological Modeller
      (STEM) which is an extensible software system and framework for modelling the
      spatial and temporal progression of multiple diseases affecting multiple
      populations in geographically distributed locations. STEM is an experiment in
      developing a software system that can model complex epidemiological scenarios
      while also being extensible by the research community. The ultimate goal of STEM
      is to provide a common modelling platform powerful enough to be sufficient for
      all modelling scenarios and extensible in a way that allows different researchers
      to combine their efforts in developing exceptionally good models. RESULTS: STEM
      is a powerful modelling system that allows researchers to model scenarios with
      unmixed populations that are not uniformly distributed and in which multiple
      populations exist that are being infected with multiple diseases. It's underlying
      representational framework, a graph, and its software architecture allow the
      system to be extended by incorporating software components developed by different
      researchers. CONCLUSION: This approach taken in the design of STEM creates a
      powerful platform for epidemiological research collaboration. Future versions of
      the system will make such collaborative efforts easy and common.

PMID- 16417634
TI  - Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and
      mediated via a mitochondrial death pathway.
AB  - BACKGROUND: The anticancer drug Ukrain (NSC-631570) which has been specified by
      the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid
      chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic
      effects on human tumour cell lines in vitro. Few clinical trials suggest
      beneficial effects in the treatment of human cancer. Aim of the present study was
      to elucidate the importance of apoptosis induction for the antineoplastic
      activity of Ukrain, to define the molecular mechanism of its cytotoxic effects
      and to identify its active constituents by mass spectrometry. METHODS: Apoptosis
      induction was analysed in a Jurkat T-lymphoma cell model by fluorescence
      microscopy (chromatin condensation and nuclear fragmentation), flow cytometry
      (cellular shrinkage, depolarisation of the mitochondrial membrane potential,
      caspase-activation) and Western blot analysis (caspase-activation). Composition
      of Ukrain was analysed by mass spectrometry and LC-MS coupling. RESULTS: Ukrain
      turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed
      that Ukrain induced depolarisation of the mitochondrial membrane potential and
      activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance
      to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced
      apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced
      apoptosis pointing to a death receptor independent signalling pathway. In
      contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced
      cell death. Moreover, over-expression of Bcl-2 or Bcl-xL and expression of
      dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing
      to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric
      analysis of Ukrain failed to detect the suggested trimeric chelidonine
      thiophosphortriamide or putative dimeric or monomeric chelidonine
      thiophosphortriamide intermediates from chemical synthesis. Instead, the
      Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine,
      protopine and allocryptopine were identified as major components of Ukrain. Apart
      from sanguinarine and chelerythrine, chelidonine turned out to be a potent
      inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while
      protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis
      signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and
      caspase-activation. CONCLUSION: The potent proapoptotic effects of Ukrain are not
      due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy of
      Chelidonium majus L. alkaloids including chelidonine.

PMID- 16417638
TI  - Expanding access to HIV prevention.

PMID- 16417639
TI  - Tooth loss and obstructive sleep apnoea.
AB  - BACKGROUND: Complete tooth loss (edentulism) produces anatomical changes that may
      impair upper airway size and function. The aim of this study was to evaluate
      whether edentulism favours the occurrence of obstructive sleep apnoea (OSA).
      METHODS: Polysomnography was performed in 48 edentulous subjects on two
      consecutive nights, one slept with and the other without dentures. Upper airway
      size was assessed by cephalometry and by recording forced mid-inspiratory airflow
      rate (FIF50). Exhaled nitric oxide (eNO) and oral NO (oNO), were measured as
      markers of airway and oropharyngeal inflammation. RESULTS: The apnoea/hypopnoea
      index (AHI) without dentures was significantly higher than with dentures (17.4 +/
      3.6 versus 11.0 +/- 2.3. p = 0.002), and was inversely related to FIF50 (p =
      0.017) and directly related to eNO (p = 0.042). Sleeping with dentures, 23
      subjects (48%) had an AHI over 5, consistent with OSA, but sleeping without
      dentures the number of subjects with abnormal AHI rose to 34 (71%). At
      cephalometry, removing dentures produced a significant decrease in
      retropharyngeal space (from 1.522 +/- 0.33 cm to 1.27 +/- 0.42 cm, p = 0.006).
      Both morning eNO and oNO were higher after the night slept without dentures (eNO
      46.1 +/- 8.2 ppb versus 33.7 +/- 6.3 ppb, p = 0.035, oNO 84.6 +/- 13.7 ppb versus
      59.2 +/- 17.4 ppb, p = 0.001). CONCLUSION: These findings suggest that complete
      tooth loss favours upper airway obstruction during sleep. This untoward effect
      seems to be due to decrease in retropharyngeal space and is associated with
      increased oral and exhaled NO concentration.

PMID- 16417641
TI  - Study protocol--diabetes and related conditions in urban indigenous people in the
      Darwin, Australia region: aims, methods and participation in the DRUID Study.
AB  - BACKGROUND: Diabetes mellitus is a serious and increasing health problem in
      Australia and is a designated national health priority. Diabetes and related
      conditions represent an even greater health burden among Indigenous Australians
      (Aborigines and Torres Strait Islanders), but there are critical gaps in
      knowledge relating to the incidence and prevalence, aetiology, and prevention of
      diabetes in this group, including a lack of information on the burden of disease
      among Indigenous people in urban areas. The DRUID Study (Diabetes and Related
      conditions in Urban Indigenous people in the Darwin region) was designed to
      address this knowledge gap. METHODS/DESIGN: The study was conducted in a
      specified geographic area in and around Darwin, Australia. Eligible participants
      underwent a health examination, including collection of blood and urine samples,
      clinical and anthropometric measurements, and administration of questionnaires,
      with an additional assessment for people with diabetes. The study was designed to
      incorporate local Indigenous leadership, facilitate community engagement, and
      provide employment and training opportunities for local Indigenous people. A
      variety of recruitment methods were used. A total of 1,004 eligible people gave
      consent and provided at least one measurement. When compared with census data for
      the Indigenous population living in the study area, there was a marked under
      representation of males, but no substantial differences in age, place of
      residence, Indigenous group, or household income. Early participants were more
      likely than later participants to have previously diagnosed diabetes. DISCUSSION:
      Despite lower than anticipated recruitment, this is, to our knowledge, the
      largest study ever conducted on the health of Indigenous Australians living in
      urban areas, a group which comprises the majority of Australia's Indigenous
      population but about whose health and wellbeing relatively little is known. The
      study is well-placed to provide new information that can be used by policy makers
      and service providers to improve the delivery of services and programs that
      affect the health of Indigenous people. It also represents a valuable opportunity
      to establish an urban Indigenous cohort study, provided participants can be
      followed successfully over time.

PMID- 16417642
TI  - Breast papillomas: current management with a focus on a new diagnostic and
      therapeutic modality.
AB  - Breast papilloma is a term that describes an intraductal papillary configuration
      of the mammary epithelium on macroscopic or microscopic examination. It includes
      solitary intraductal papillomas, multiple papillomas, papillomatosis, and
      juvenile papillomatosis (JP).Recent advances in mammary ductoscopy (MD) have
      raised new possibilities in the diagnosis and treatment of breast papillomas.
      This technique represents an important diagnostic adjunct in patients with
      pathological nipple discharge (PND) by allowing direct visualisation and biopsy
      of intraductal lesions and guiding duct excision surgery. Treatment of breast
      papillomas often entails surgical duct excision for symptomatic relief and
      histopathological examination. Recently, more conservative approach has been
      adapted. MD-assisted microdochectomy should be considered the procedure of choice
      for a papilloma-related single duct discharge. Furthermore, there is increasing
      evidence that MD has the potential to reduce the number of duct excision
      procedures and minimise the extent of surgical resection. Imaging-guided vacuum
      assisted core biopsy can be diagnostic and therapeutic for papillomas seen on
      mammography and/or ultrasound. Patients with multiple papillomas do have an
      increased risk of developing cancer and should be kept under annual review with
      regular mammography (preferably digital mammography) if treated conservatively.
      Magnetic resonance (MR) can be also used in surveillance in view of its high
      sensitivity. Because the risk is small, long term and affects both breasts, long
      term follow-up is more appropriate than prophylactic mastectomy. Patients who
      prove to have solitary duct papilloma have insufficient increase in the risk of
      subsequent malignancy to justify routine follow-up.

PMID- 16417643
TI  - preAssemble: a tool for automatic sequencer trace data processing.
AB  - BACKGROUND: Trace or chromatogram files (raw data) are produced by automatic
      nucleic acid sequencing equipment or sequencers. Each file contains information
      which can be interpreted by specialised software to reveal the sequence (base
      calling). This is done by the sequencer proprietary software or publicly
      available programs. Depending on the size of a sequencing project the number of
      trace files can vary from just a few to thousands of files. Sequencing quality
      assessment on various criteria is important at the stage preceding clustering and
      contig assembly. Two major publicly available packages--Phred and Staden are used
      by preAssemble to perform sequence quality processing. RESULTS: The preAssemble
      pre-assembly sequence processing pipeline has been developed for small to large
      scale automatic processing of DNA sequencer chromatogram (trace) data. The Staden
      Package Pregap4 module and base-calling program Phred are utilized in the
      pipeline, which produces detailed and self-explanatory output that can be
      displayed with a web browser. preAssemble can be used successfully with very
      little previous experience, however options for parameter tuning are provided for
      advanced users. preAssemble runs under UNIX and LINUX operating systems. It is
      available for downloading and will run as stand-alone software. It can also be
      accessed on the Norwegian Salmon Genome Project web site where preAssemble jobs
      can be run on the project server. CONCLUSION: preAssemble is a tool allowing to
      perform quality assessment of sequences generated by automatic sequencing
      equipment. preAssemble is flexible since both interactive jobs on the preAssemble
      server and the stand alone downloadable version are available. Virtually no
      previous experience is necessary to run a default preAssemble job, on the other
      hand options for parameter tuning are provided. Consequently preAssemble can be
      used as efficiently for just several trace files as for large scale sequence
      processing.

PMID- 16417645
TI  - Physical anhedonia in the acute phase of schizophrenia.
AB  - BACKGROUND: The aim of the current study is to investigate the relationship
      between physical anhedonia and psychopathological parameters, pharmacological
      parameters or motor side-effects in a sample of inpatients with schizophrenia in
      an acute episode of their illness. METHOD: Eighty one patients with
      schizophrenia, consecutively admitted, with an acute episode of their illness, at
      the Eginition Hospital, Department of Psychiatry, University of Athens, during a
      one-year period were investigated regarding possible relationships between
      physical anhedonia, social-demographic data and clinical parameters as well as
      motor side-effects, induced by antipsychotic agents. All patients were assessed
      using the Chapman Revised Physical Anhedonia Scale (RPAS), the Positive and
      Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side-Effects
      (EPSE), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary
      Movement Scale (AIMS). Simple cross tabulations were initially employed.
      Subsequently, multiple regression analysis was performed. RESULTS: Both positive
      and negative symptoms were associated with physical anhedonia. A positive
      association between physical anhedonia and the non-paranoid sub-category of
      schizophrenia was also proved. CONCLUSION: According to these results, it seems
      that in the acute phase of schizophrenia, physical anhedonia may be a
      contributing factor to patient's psychopathology.

PMID- 16417644
TI  - Evidence of host-virus co-evolution in tetranucleotide usage patterns of
      bacteriophages and eukaryotic viruses.
AB  - BACKGROUND: Virus taxonomy is based on morphologic characteristics, as there are
      no widely used non-phenotypic measures for comparison among virus families. We
      examined whether there is phylogenetic signal in virus nucleotide usage patterns
      that can be used to determine ancestral relationships. The well-studied model of
      tail morphology in bacteriophage classification was used for comparison with
      nucleotide usage patterns. Tetranucleotide usage deviation (TUD) patterns were
      chosen since they have previously been shown to contain phylogenetic signal
      similar to that of 16S rRNA. RESULTS: We found that bacteriophages have unique
      TUD patterns, representing genomic signatures that are relatively conserved among
      those with similar host range. Analysis of TUD-based phylogeny indicates that
      host influences are important in bacteriophage evolution, and phylogenies
      containing both phages and their hosts support their co-evolution. TUD-based
      phylogeny of eukaryotic viruses indicates that they cluster largely based on
      nucleic acid type and genome size. Similarities between eukaryotic virus
      phylogenies based on TUD and gene content substantiate the TUD methodology.
      CONCLUSION: Differences between phenotypic and TUD analysis may provide clues to
      virus ancestry not previously inferred. As such, TUD analysis provides a
      complementary approach to morphology-based systems in analysis of virus
      evolution.

PMID- 16417646
TI  - A case of bone metastasis of colon cancer that markedly responded to S-1/CPT-11
      combination chemotherapy and became curable by resection.
AB  - BACKGROUND: An oral combined fluoropyrimidine anticancer drug,
      tegafur/gimeracil/oteracil potassium (S-1), has recently been used alone or in
      combination for colon cancer. CASE PRESENTATION: The patient was a 42-year-old
      man with sigmoid colon cancer with direct invasion of the urinary bladder and
      multiple costal metastases. A diagnosis of T4, M1, stage IV sigmoid colon cancer
      was made, and curative resection was considered impossible. S-1 at 50 mg/m2 was
      administered by oral route from day 1 to day 14. Irinotecan (CPT-11) at 40 mg/m2
      was administered by intravenous day 1 and 15. This treatment was followed by 2
      weeks absent period, and repeated every 4 weeks. Six cycles of administration
      were performed in total. Following this treatment, the multiple costal metastases
      resolved. Down-staging to T3, M0, stage IIA was achieved, and curative resection
      was judged to be possible. CONCLUSION: Occasional cases in which S-1/CPT-11
      therapy was effective have been recently reported. The patient's tumor became
      resectable despite the discovery of colon cancer associated with bone metastasis
      at the initial examination, offering hope for cancer patients.

PMID- 16417647
TI  - Recovery and evolutionary analysis of complete integron gene cassette arrays from
      Vibrio.
AB  - BACKGROUND: Integrons are genetic elements capable of the acquisition,
      rearrangement and expression of genes contained in gene cassettes. Gene cassettes
      generally consist of a promoterless gene associated with a recombination site
      known as a 59-base element (59-be). Multiple insertion events can lead to the
      assembly of large integron-associated cassette arrays. The most striking examples
      are found in Vibrio, where such cassette arrays are widespread and can range from
      30 kb to 150 kb. Besides those found in completely sequenced genomes, no such
      array has yet been recovered in its entirety. We describe an approach to
      systematically isolate, sequence and annotate large integron gene cassette arrays
      from bacterial strains. RESULTS: The complete Vibrio sp. DAT722 integron cassette
      array was determined through the streamlined approach described here. To place it
      in an evolutionary context, we compare the DAT722 array to known vibrio arrays
      and performed phylogenetic analyses for all of its components (integrase, 59-be
      sites, gene cassette encoded genes). It differs extensively in terms of genomic
      context as well as gene cassette content and organization. The phylogenetic tree
      of the 59-be sites collectively found in the Vibrio gene cassette pool suggests
      frequent transfer of cassettes within and between Vibrio species, with slower
      transfer rates between more phylogenetically distant relatives. We also identify
      multiple cases where non-integron chromosomal genes seem to have been assembled
      into gene cassettes and others where cassettes have been inserted into
      chromosomal locations outside integrons. CONCLUSION: Our systematic approach
      greatly facilitates the isolation and annotation of large integrons gene cassette
      arrays. Comparative analysis of the Vibrio sp. DAT722 integron obtained through
      this approach to those found in other vibrios confirms the role of this genetic
      element in promoting lateral gene transfer and suggests a high rate of gene
      gain/loss relative to most other loci on vibrio chromosomes. We identify a
      relationship between the phylogenetic distance separating two species and the
      rate at which they exchange gene cassettes, interactions between the non-mobile
      portion of bacterial genomes and the vibrio gene cassette pool as well as
      intragenomic translocation events of integrons in vibrios.

PMID- 16417648
TI  - Spontaneous apoptosis of blood dendritic cells in patients with breast cancer.
AB  - INTRODUCTION: Dendritic cells (DCs) are key antigen-presenting cells that play an
      essential role in initiating and directing cellular and humoral immunity,
      including anti-tumor responses. Due to their critical role in cancer, induction
      of DC apoptosis may be one of the central mechanisms used by tumors to evade
      immune recognition. METHODS: Spontaneous apoptosis of blood DCs (lineage negative
      HLA-DR positive cells) was assessed in peripheral blood mononuclear cells (PBMCs)
      using Annexin-V and TUNEL assays immediately after blood collection. The role of
      tumor products was assessed by culturing cells with supernatants derived from
      breast cancer cell lines (TDSN) or PBMCs (PBMC-SN, as a control). The capacity of
      DC stimulation to prevent apoptosis was assessed by incubating DC with
      inflammatory cytokines, poly I:C, IL-12 or CD40 ligand (CD40L) prior to culture
      with TDSN. Apoptosis was determined by flow cytometry and microscopy, and Bcl-2
      expression determined by intracellular staining. RESULTS: In this study we
      document the presence of a significantly higher proportion of apoptotic (Annexin
      V+ and TUNEL+) blood DCs in patients with early stage breast cancer (stage I to
      II; n = 13) compared to healthy volunteers (n = 15). We examined the role of
      tumor products in this phenomenon and show that supernatants derived from breast
      cancer lines induce apoptosis of blood DCs in PBMC cultures. Aiming to identify
      factors that protect blood DC from apoptosis, we compared a range of clinically
      available maturation stimuli, including inflammatory cytokines (tumor necrosis
      factor-alpha, IL-1beta, IL-6 and prostaglandin (PG)E2 as a cytokine cocktail),
      synthetic double-stranded RNA (poly I:C) and soluble CD40 ligand. Although
      inflammatory cytokines and poly I:C induced robust phenotypic maturation, they
      failed to protect blood DCs from apoptosis. In contrast, CD40 stimulation induced
      strong antigen uptake, secretion of IL-12 and protected blood DCs from apoptosis
      through sustained expression of Bcl-2. Exogenous IL-12 provided similar Bcl-2
      mediated protection, suggesting that CD40L effect is mediated, at least in part,
      through IL-12 secretion. CONCLUSION: Cumulatively, our results demonstrate
      spontaneous apoptosis of blood DCs in patients with breast cancer and confirm
      that ex vivo conditioning of blood DCs can protect them from tumor-induced
      apoptosis.

PMID- 16417649
TI  - New role for nuclear hormone receptors and coactivators in regulation of BRCA1
      mediated DNA repair in breast cancer cell lines.
AB  - INTRODUCTION: The breast cancer susceptibility gene BRCA1 is involved in the
      repair of double-strand breaks induced by ionizing radiation and chemotherapy
      drugs. BRCA1 interacts with coactivators such as p300 and CREB-binding protein
      (CBP) to activate target gene transcription. Estrogen and retinoic acid receptors
      (ER and RAR) also require coactivator proteins for their ligand-dependent
      functions. Few studies have suggested a role for nuclear hormone receptors in DNA
      repair. METHODS: DNA damage and repair activity were quantified with the use of
      single-cell gel electrophoresis and plasmid end-joining assays. Cell cycle
      progression and apoptosis were determined by bromodeoxyuridine and TdT-mediated
      dUTP nick end labelling assays. Stable transfection was accomplished with the
      lipofection procedure. Protein interaction and expression were determined by
      immunoprecipitation and western blotting. RESULTS: 17beta-estradiol (E2) and all
      trans retinoic acid (RA) had opposing effects on DNA damage and breast cancer
      cell survival after double-strand break damage. Treatment with E2, but not with
      RA, resulted in complex formation between ERalpha, CBP, and BRCA1 in ER-positive
      cell lines. Mutant BRCA1 reduced the expression and activity of DNA damage repair
      proteins but did not block nuclear hormone-dependent effects. Mutant BRCA1 failed
      to form complexes with ERalpha and CBP, which correlated with its ability to
      exert E2-independent effects on DNA repair. Mutant BRCA1 inhibited cell cycle
      progression and produced increased survival in cells with double-strand breaks.
      Ectopic ERalpha expression reproduced the E2-mediated effects on DNA damage,
      repair, and survival. CONCLUSION: The present study proposes a new mechanism by
      which ER and RAR regulate BRCA1-mediated DNA repair by means of CBP.

PMID- 16417650
TI  - Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen
      receptor-positive breast cancer cell lines.
AB  - INTRODUCTION: Bisphosphonates are inhibitors of osteoclast-mediated tumor
      stimulated osteolysis, and they have become standard therapy for the management
      of bone metastases from breast cancer. These drugs can also directly induce
      growth inhibition and apoptosis of osteotropic cancer cells, including estrogen
      receptor-positive (ER+) breast cancer cells. METHODS: We examined the anti
      proliferative properties of ibandronate on two ER+ breast cancer cell lines (MCF
      7 and IBEP-2), and on one ER negative (ER-) cell line (MDA-MB-231). Experiments
      were performed in steroid-free medium to assess ER regulation and the effect of
      ibandronate in combination with estrogen or antiestrogens. RESULTS: Ibandronate
      inhibited cancer cell growth in a dose- and time-dependent manner (approximate
      IC50: 10(-4) M for MCF-7 and IBEP-2 cells; 3 x 10(-4) M for MDA-MB-231 cells),
      partly through apoptosis induction. It completely abolished the mitogenic effect
      induced by 17beta-estradiol in ER+ breast cancer cells, but affected neither ER
      regulation nor estrogen-induced progesterone receptor expression, as documented
      in MCF-7 cells. Moreover, ibandronate enhanced the growth inhibitory action of
      partial (4-hydroxytamoxifen) and pure (ICI 182,780, now called fluvestrant or
      Faslodex) antiestrogens in estrogen-sensitive breast cancer cells. Combination
      analysis identified additive interactions between ibandronate and ER antagonists.
      CONCLUSION: These data constitute the first in vitro evidence for additive
      effects between ibandronate and antiestrogens, supporting their combined use for
      the treatment of bone metastases from breast cancer.

PMID- 16417651
TI  - Hormone replacement therapy and false positive recall in the Million Women Study:
      patterns of use, hormonal constituents and consistency of effect.
AB  - INTRODUCTION: Current and recent users of hormone replacement therapy (HRT) have
      an increased risk of being recalled to assessment at mammography without breast
      cancer being diagnosed ('false positive recall'), but there is limited
      information on the effects of different patterns of HRT use on this. The aim of
      this study is to investigate in detail the relationship between patterns of use
      of HRT and false positive recall. METHODS: A total of 87,967 postmenopausal women
      aged 50 to 64 years attending routine breast cancer screening at 10 UK National
      Health Service Breast Screening Units from 1996 to 1998 joined the Million Women
      Study by completing a questionnaire before screening and were followed for their
      screening outcome. RESULTS: Overall, 399 (0.5%) participants were diagnosed with
      breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users
      of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62
      (1.43-1.83), 1.80 (1.62-2.01) and 0.76 (0.52-1.10) in current users of oestrogen
      only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity)
      < 0.0001); 1.65 (1.43-1.91), 1.49 (1.22-1.81) and 2.11 (1.45-3.07) for current
      HRT used orally, transdermally or via an implant, respectively (p (heterogeneity)
      = 0.2); and 1.84 (1.67-2.04) and 1.75 (1.49-2.06) for sequential and continuous
      oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative
      risk of false positive recall among current users appeared to increase with
      increasing time since menopause, but did not vary significantly according to any
      other factors examined, including duration of use, hormonal constituents, dose,
      whether single- or two-view screening was used, or the woman's personal
      characteristics. CONCLUSION: Current use of oestrogen-only and oestrogen
      progestagen HRT, but not tibolone, increases the risk of false positive recall at
      screening.

PMID- 16417652
TI  - BRCA1 and BRCA2 mutation predictions using the BOADICEA and BRCAPRO models and
      penetrance estimation in high-risk French-Canadian families.
AB  - INTRODUCTION: Several genetic risk models for breast and ovarian cancer have been
      developed, but their applicability to specific populations has not been
      evaluated. We used data from French-Canadian families to evaluate the mutation
      predictions given by the BRCAPRO and BOADICEA models. We also used this data set
      to estimate the age-specific risks for breast and ovarian cancer in BRCA1 and
      BRCA2 mutation carriers. METHODS: A total of 195 families with multiple affected
      individuals with breast or ovarian cancer were recruited through the INHERIT
      (INterdisciplinary HEalth Research International Team on BReast CAncer
      susceptibility) BRCAs research program. Observed BRCA1 and BRCA2 mutation status
      was compared with predicted carrier probabilities under the BOADICEA and BRCAPRO
      models. The models were assessed using Brier scores, attributes diagrams and
      receiver operating characteristic curves. Log relative risks for breast and
      ovarian cancer in mutation carriers versus population risks were estimated by
      maximum likelihood, using a modified segregation analysis implemented in the
      computer program MENDEL. Twenty-five families were eligible for inclusion in the
      BRCA1 penetrance analysis and 27 families were eligible for the BRCA2 penetrance
      analysis. RESULTS: The BOADICEA model predicted accurately the number of BRCA1
      and BRCA2 mutations for the various groups of families, and was found to
      discriminate well at the individual level between carriers and noncarriers.
      BRCAPRO over-predicted the number of mutations in almost all groups of families,
      in particular the number of BRCA1 mutations. It significantly overestimated the
      carrier frequency for high predicted probabilities. However, it discriminated
      well between carriers and noncarriers. Receiver operating characteristic (ROC)
      curves indicate similar sensitivity and specificity for BRCAPRO and BOADICEA. The
      estimated risks for breast and ovarian cancer in BRCA1 and BRCA2 mutation
      carriers were consistent with previously published estimates. CONCLUSION: The
      BOADICEA model predicts accurately the carrier probabilities in French-Canadian
      families and may be used for counselling in this population. None of the
      penetrance estimates was significantly different from previous estimates,
      suggesting that previous estimates may be appropriate for counselling in this
      population.

PMID- 16417653
TI  - Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced
      breast cancer patients exposed to trastuzumab plus chemotherapy.
AB  - INTRODUCTION: The amounts of estrogen receptor (ER) and progesterone receptor
      (PgR) in a primary tumor are predictive of the response to endocrine therapies of
      breast cancer. Several patients with ER-positive primary tumors relapse after
      adjuvant endocrine therapy with no ER expression in the recurrent tissue; much
      fewer with a recurrent disease after an ER-negative primary tumor may become
      endocrine responsive. These sequences of events indicate that a phenotype based
      on ER expression may not be a permanent feature of breast cancer. METHODS: Ten
      patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER
      or PgR, were treated with weekly trastuzumab at standard doses with or without
      chemotherapy. RESULTS: Three out of 10 patients showed overexpression of ERs
      first appearing after 9, 12 and 37 weeks, respectively, from the initiation of
      trastuzumab. Two of these patients were subsequently treated with endocrine
      therapy alone: one of them received letrozole for 3 years without evidence of
      progression. CONCLUSION: Therapeutic targets enabling the appearance of an
      endocrine responsive disease may increase treatment options for patients with
      breast cancer. Furthermore, these clinical data suggest that an ER-negative
      phenotype is a multi-step process with a reversible repression modality, and that
      some ER-negative tumors may either revert to an ER-positive phenotype, allowing
      an endocrine treatment to be effective.

PMID- 16417654
TI  - Hormones, receptors, and growth in hyperplastic enlarged lobular units: early
      potential precursors of breast cancer.
AB  - INTRODUCTION: The hyperplastic enlarged lobular unit (HELU) is a common
      alteration in adult female human breast and is the earliest histologically
      identifiable lesion with premalignant potential. Growth and differentiation in
      normal epithelium are regulated by estrogen and progesterone, whose effects are
      mediated through estrogen receptor (ER)-alpha and progesterone receptor (PR). We
      assessed correlations between growth (proliferation and apoptosis), endogenous
      hormone levels (using age as a surrogate for menopausal/estrogen status), and ER
      alpha/PR expression in HELUs versus adjacent normal terminal duct lobular units
      (TDLUs) to gain insight into potentially premalignant hyperplasia. METHODS:
      Proliferation (Ki67 antigen), ER-alpha, and PR were assessed by
      immunohistochemistry, apoptosis using the TUNEL (terminal transferase-mediated
      dUTP nick end-labeling) assay, and nuclear colocalization of ER-alpha and Ki67 by
      dual-labeled immunofluorescence in HELUs and adjacent TDLUs (n = 100-584,
      depending on the factor) from 324 breasts. All factors were quantified under
      direct microscopic visualization. ER-alpha/PR expression was semiquantified by
      estimating the proportion of positive cells (0 = none, 1 = or <1/100, 2 = 1/100
      to 1/10, 3 = 1/10 to 1/3, 4 = 1/3 to 2/3, and 5 = or >2/3). Ki67, TUNEL, and
      colocalization of ER-alpha and Ki67 were scored by absolute counting (%positive).
      RESULTS: ER-alpha and PR expression were significantly elevated in HELUs versus
      adjacent TLDUs (average score: 4.5 versus 3.1 and 3.5 versus 2.1; P < 0.0001).
      Proliferation was also significantly higher in HELUs versus TDLUs (average 6.3%
      versus 2.0%; P < 0.0001). In contrast, apoptosis was significantly lower in HELUs
      versus TDLUs (average 0.61% versus 0.22%; P < 0.0001). Changes in proliferation
      and receptor expression were similar between premenopausal and postmenopausal
      TDLUs and HELUs, suggesting that hyperplastic cells remain responsive to
      regulation by estrogen. The proportion of ER-positive/proliferating cells was
      much higher in HELUs than TDLUs (27.6% vs. 4.9%; P < .0001). CONCLUSION:
      Development of HELUs is associated with increased proliferation and decreased
      cell death relative to normal cells. ER-alpha and PR are highly elevated in
      HELUs, which may contribute to the hyperplasia because they mediate hormonal
      regulation of growth. An understanding of the fundamental causes of increased
      levels of receptors and growth may lead to new strategies to prevent breast
      cancer.

PMID- 16417655
TI  - Comprehensive copy number profiles of breast cancer cell model genomes.
AB  - INTRODUCTION: Breast cancer is the most commonly diagnosed cancer in women
      worldwide and consequently has been extensively investigated in terms of
      histopathology, immunochemistry and familial history. Advances in genome-wide
      approaches have contributed to molecular classification with respect to genomic
      changes and their subsequent effects on gene expression. Cell lines have provided
      a renewable resource that is readily used as model systems for breast cancer cell
      biology. A thorough characterization of their genomes to identify regions of
      segmental DNA loss (potential tumor-suppressor-containing loci) and gain
      (potential oncogenic loci) would greatly facilitate the interpretation of
      biological data derived from such cells. In this study we characterized the
      genomes of seven of the most commonly used breast cancer model cell lines at
      unprecedented resolution using a newly developed whole-genome tiling path genomic
      DNA array. METHODS: Breast cancer model cell lines MCF-7, BT-474, MDA-MB-231,
      T47D, SK-BR-3, UACC-893 and ZR-75-30 were investigated for genomic alterations
      with the submegabase-resolution tiling array (SMRT) array comparative genomic
      hybridization (CGH) platform. SMRT array CGH provides tiling coverage of the
      human genome permitting break-point detection at about 80 kilobases resolution.
      Two novel discrete alterations identified by array CGH were verified by
      fluorescence in situ hybridization. RESULTS: Whole-genome tiling path array CGH
      analysis identified novel high-level alterations and fine-mapped previously
      reported regions yielding candidate genes. In brief, 75 high-level gains and 48
      losses were observed and their respective boundaries were documented. Complex
      alterations involving multiple levels of change were observed on chromosome arms
      1p, 8q, 9p, 11q, 15q, 17q and 20q. Furthermore, alignment of whole-genome
      profiles enabled simultaneous assessment of copy number status of multiple
      components of the same biological pathway. Investigation of about 60 loci
      containing genes associated with the epidermal growth factor family (epidermal
      growth factor receptor, HER2, HER3 and HER4) revealed that all seven cell lines
      harbor copy number changes to multiple genes in these pathways. CONCLUSION: The
      intrinsic genetic differences between these cell lines will influence their
      biologic and pharmacologic response as an experimental model. Knowledge of
      segmental changes in these genomes deduced from our study will facilitate the
      interpretation of biological data derived from such cells.

PMID- 16417656
TI  - CD24 staining of mouse mammary gland cells defines luminal epithelial,
      myoepithelial/basal and non-epithelial cells.
AB  - INTRODUCTION: Breast cancer is thought to arise in mammary epithelial stem cells.
      There is, therefore, a large amount of interest in identifying these cells. The
      breast is a complex tissue consisting of two epithelial layers (an outer
      myoepithelial/basal layer and an inner luminal epithelial layer) as well as a
      large non-epithelial component (fibroblasts, endothelial cells, lymphocytes,
      adipocytes, neurons and myocytes). The definitive identification of a mammary
      epithelial stem cell population is critically dependent on its purity. To date,
      this has been hampered by the lack of suitable markers to separate out the two
      epithelial layers, and to remove contaminating non-epithelial cells. METHODS:
      Mouse mammary glands were dissociated and stained with CD24. Cells were sorted
      into separate populations based on CD24 expression and assessed for luminal
      epithelial and myoepithelial/basal markers by direct fluorescent microscopy and
      real time PCR. The stem/progenitor potential of these cell populations was
      assessed in vivo by cleared mammary fat pad transplantation. RESULTS: Three
      populations of CD24 expressing cells were identified: CD24Negative, CD24Low and
      CD24High. Staining of these cells with cytokeratin markers revealed that these
      populations correspond to non-epithelial, myoepithelial/basal and luminal
      epithelial cells, respectively. Cell identities were confirmed by quantitative
      PCR. Cleared mammary fat pad transplantation of these cell populations revealed
      that extensive mammary fat pad repopulation capacity segregates with the CD24Low
      cells, whilst CD24High cells have limited repopulation capacity. CONCLUSION:
      Differential staining of mammary epithelial cells for CD24 can be used to
      simultaneously isolate pure populations of non-epithelial, myoepithelial/basal
      and luminal epithelial cells. Furthermore, mammary fat pad repopulation capacity
      is enriched in the CD24Low population. As separation is achieved using a single
      marker, it will be possible to incorporate additional markers to further
      subdivide these populations. This will considerably facilitate the further
      analysis of mammary epithelial subpopulations, whilst ensuring high purity, which
      is key for understanding mammary epithelial stem cells in normal tissue biology
      and carcinogenesis.

PMID- 16417657
TI  - The evolving paradigm of tissue-specific metastasis.

PMID- 16417659
TI  - Light at the end of the tunnel for the blind leading the blind?

PMID- 16417658
TI  - Co-expression of estrogen receptor-alpha and targets of estrogen receptor action
      in proliferating monkey mammary epithelial cells.
AB  - INTRODUCTION: Failure to detect co-expression of estrogen receptor-alpha
      (ERalpha) and proliferation 'markers' such as Ki67 in human mammary epithelium
      led to the view that estrogen acts indirectly to stimulate mammary epithelial
      proliferation. The mitotic index was so low in prior studies, however, that
      transient co-expression of ERalpha and Ki67 during the cell cycle could have been
      below detection limits. METHODS: Immunohistochemistry was used on mammary tissue
      sections from estrogen treated rhesus monkeys to investigate co-expression of
      ERalpha and the proliferation antigen Ki67. Using the same methods, we
      investigated the cell localization of proteins involved in estrogen-induced
      proliferation, including cyclin D1, stromal cell-derived factor (SDF)-1, and MYC.
      RESULTS: ERalpha was co-expressed with the proliferation marker Ki67 as well as
      with SDF-1, MYC and cyclin D1 in mammary epithelial cells from estrogen-treated
      monkeys. CONCLUSION: ERalpha is expressed in proliferating mammary epithelial
      cells together with the estrogen-induced proteins MYC, cyclin D1 and SDF-1,
      consistent with a direct mitogenic action by estrogen in primate mammary
      epithelium.

PMID- 16417660
TI  - Autism and newborn encephalopathy.

PMID- 16417662
TI  - Long-term survival for a cohort of adults with cerebral palsy.
AB  - The aim of this study was to investigate long-term survival and examine causes of
      death in adult patients with cerebral palsy (CP). A 1940-1950 birth cohort based
      on paediatric case referral allows for long-term survival follow-up. Survival is
      analyzed by birth characteristics and severity of disability from age 20 years
      (and age 2y for a subset of the data). Survival outcome compared with that
      expected in the general population based on English life tables. The main cohort
      consisted of 341 individuals, with 193 males and 148 females. Conditional on
      surviving to age 20 years, almost 85% of the cohort survived to age 50 years (a
      comparable estimate for the general population is 96%). Very few deaths were
      attributed to CP for those people dying over 20 years of age. Females survived
      better than males. However, females faced a greater increase in risk relative to
      the general population than did males. We conclude that survival outlook is good
      though lower than in the general population. The relative risk of death compared
      with the UK population decreases with age, although it shows some indication of
      rising again after age 50 years. Many more deaths were caused by diseases of the
      respiratory system among those dying in their 20s and 30s than would be expected
      in the general population. Many fewer deaths than expected in this age group are
      caused by injuries and accidents. For those people who die in their 40s and 50s,
      an increase in deaths due to diseases of the circulatory system and neoplasms is
      observed. More deaths than expected in this age group are due to diseases of the
      nervous system.

PMID- 16417661
TI  - Autism following a history of newborn encephalopathy: more than a coincidence?
AB  - Between June 1993 and December 1996, 276 term newborn infants with encephalopathy
      and 564 randomly selected term controls were enrolled in a population-based study
      of moderate and severe term newborn encephalopathy (NE) in Western Australia.
      During comprehensive neurobehavioural and cognitive follow-up of all patients and
      controls at 3 years and again at 5 years of age we found an unexpected but strong
      association between NE and autism spectrum disorders (ASDs). A diagnosis of ASD
      by age 5 years was reached using criteria according of the Diagnostic Statistical
      Manual, 4th edition. Linking records to the Western Australian Disability
      Services Commission Register ensured that no child in the study with ASD was
      missed. By age 5 years, 37 (13.4%) infants with NE and one (0.2%) control had
      died. Among the 239 survivors of NE, 12 (5%) were diagnosed with an ASD. Of
      these, 10 (4.2%) met the full criteria for autism, one had pervasive
      developmental disorder-not otherwise specified, and one had Asperger syndrome.
      Among the 563 surviving controls, five (0.8%) were diagnosed with an ASD: three
      with autism, one with autism/possible Asperger syndrome, and one with Asperger
      syndrome. Compared with the controls, the children who had experienced NE were
      5.9 times (95% confidence interval 2.0-16.9) more likely to have been diagnosed
      with an ASD.

PMID- 16417663
TI  - Transient dystonic toe-walking: differentiation from cerebral palsy and a rare
      explanation for some unexplained cases of idiopathic toe-walking.
AB  - We report on seven children (five males, two females) who presented with marked,
      often asymmetrical, toe-walking from onset of independent walking, associated
      with abnormal foot postures and increased tone at the ankles with characteristics
      of dystonia. Most of the children had presented with unusual pre-walking
      locomotion and a mild delay in independent walking. They did not fit into the
      usual categories of 'habitual' toe-walking or congenital short tendo calcaneus
      but nor did they have the clinical signs of spastic diplegia or of a peripheral
      neuromuscular disease. Normalization occurred progressively in the second to
      fourth years of life. The children were re-examined several years later (1 to
      11y) and were normal. We believe that their persistent toe-walking corresponded
      to a variant of 'transient focal dystonia of infancy'. Knowledge of its existence
      may justify a period of observation without special investigations, surgery, or
      casting.

PMID- 16417664
TI  - Drooling in children with cerebral palsy: effect of salivary flow reduction on
      daily life and care.
AB  - The purpose of this study was to investigate the effect of salivary flow
      reduction on daily life and provision of care in children with cerebral palsy
      (CP). Parents of children with CP were asked to fill in a questionnaire on the
      impact of drooling on the daily life of their children and their families and the
      data were then analyzed. Forty-five children with severe drooling (28 males, 17
      females; mean age 9y 5mo [SD 3y 7mo]; range 3 to 16y) were monitored before and
      after receiving medication (scopolamine and botulinum toxin) to reduce salivary
      flow. Type of CP included hypotonia (n = 1), spastic paresis (n = 27), and mixed
      motor disorders with spastic and dyskinetic paresis (n = 17). Eight children were
      independently ambulant and 37 children were wheelchair users. Thirty-four
      children had learning disability with a developmental age of below 6 years. Six
      participants dropped out of the study; data on 39 children were analyzed. Results
      showed that anticholinergic agents effectively reduced salivary flow. Drooling
      diminished substantially and this was accompanied by a significant reduction in
      care needs, making daily care less demanding. The amount of reported damage to
      communication devices and computers decreased. In addition to the evaluation of
      primary variables, such as the salivary flow rate, investigation of impact of
      drooling on daily life provides useful information about the outcome of treatment
      for reduction in drooling.

PMID- 16417665
TI  - Questionnaire for assessing parents' concerns about their child with
      hydrocephalus.
AB  - The many concerns of parents of children with hydrocephalus have not previously
      been assessed using a reliable, quantitative measurement. The development and
      preliminary use of a questionnaire to measure the concerns of these parents is
      reported. A general health status measure for hydrocephalus was developed
      concurrently. Items were generated primarily from parent focus groups resulting
      in a comprehensive list of 22 unique parental concern items. The most important
      of these items, as selected by another sample of parents of 60 children (27
      females, 33 males; mean age 8y 4mo, [SD 4y 6mo]) were retained for the final
      questionnaire. This 9-item parental concerns questionnaire was tested for
      reliability and construct validity (by assessing correlations with various
      independent measures of health status, including Health Utilities Index-2 and
      Impact-on-Family Scale) using a cohort consisting of the parents of 80 children
      (39 females, 41 males; mean age 10y, [SD 3y 6mo]). An exploratory analysis was
      performed to determine which patient variables were associated with greater
      parental concern. The parental concerns questionnaire demonstrated excellent test
      retest reliability (0.86, 95% CI 0.77-0.92) and internal consistency (Cronbach's
      alpha=0.89). As expected, interrater reliability was somewhat lower (0.67, 95% CI
      0.49-0.79). Construct validity was demonstrated by consistently moderate
      Pearson's correlations with several independent measures of the child's health.
      The presence of epilepsy and younger patient age appeared to be significantly
      associated with greater parental concern. This new questionnaire has demonstrated
      very good psychometric properties. It can be used to broaden the scope of future
      clinical research in pediatric hydrocephalus to include the impact on parents.

PMID- 16417666
TI  - Functional independence among young adults with spina bifida, in relation to
      hydrocephalus and level of lesion.
AB  - Knowledge about the level of functional independence that can be expected in
      adulthood might support decisions on the treatment of newborn infants with spina
      bifida. This study determined functional independence among young adults with
      spina bifida and its relationships with pathological characteristics known from
      birth (hydrocephalus and level of lesion). Data were collected from medical
      records and by physical examination. Functional independence was assessed on six
      domains (self-care, sphincter control, transfers, locomotion, communication, and
      social cognition) using the Functional Independence Measure (FIM). Participants
      were 165 patients with spina bifida (69 males, 96 females; age range 16 to 25y,
      mean 20y 9mo [SD 2.9]; 117 with hydrocephalus). Patients without hydrocephalus
      were independent for all FIM domains except sphincter control, as were patients
      with hydrocephalus with a lesion level below L2. Most patients with hydrocephalus
      and a lesion at L2 or above were dependent as regards sphincter control (98%),
      locomotion (79%), and self-care (54%), and quite a few needed support in
      transfers (38%), social cognition (29%), and communication (15%).

PMID- 16417667
TI  - Assessment of unilateral spatial neglect in children using the Teddy Bear
      Cancellation Test.
AB  - The purpose of the study was to provide normative data for the Teddy Bear
      Cancellation Test (TBCT) and to evaluate prospectively the frequency of
      unilateral spatial neglect (USN) in children with acquired brain injury (ABI). In
      the control group (n = 419; 218 males, 201 females; mean age 5y 1mo [SD 1y 4mo];
      range 3 to 8y) omissions were rare and decreased with age. A left displacement of
      the first three teddy bears cancelled was observed with increasing age. This
      preferential left-to-right cancelling strategy was interpreted as learned under
      the influence of reading habits. The same test was used prospectively in 41
      children with ABI (24 males, 17 females; mean age 5y 5mo [SD 2y]; range 3 to 8y)
      admitted to a paediatric rehabilitation department specializing in acquired brain
      lesions. In patients and controls, children under 6 years of age omitted more
      items than older children. The localization of omissions was skewed significantly
      to the left in children with right-sided lesions compared with children with left
      sided lesions. USN was observed in seven patients with ABI. Left USN was found in
      three of the 10 patients with right-sided ABI. Right USN was present in two of
      the patients with 15 left-sided ABI and two of the 16 patients with non
      lateralized ABI. Left USN is frequent in children after right-sided brain injury.
      The relatively high incidence of right spatial neglect in children is discussed
      in relation to the development of hemispheric specialization.

PMID- 16417668
TI  - Evidence from two genetic syndromes for the independence of spatial and visual
      working memory.
AB  - This study aimed at investigating the possible dissociation between visual-object
      and visual-spatial working memory (WM) in individuals with Williams syndrome (WS)
      and Down syndrome (DS). Four study groups were included: WS group (10 males, 5
      females) with a mean chronological age (CA) of 19 years 8 months (SD 6y 1mo) and
      a mean mental age (MA)of 6 years 11 months (SD 1y 5mo); WS comparison group (7
      males, 8 females) comprised of typically developing children with a mean CA of 6
      years 10 months (SD 10mo) and a mean MA of 6 years 11 months (SD 8mo)matched as a
      group with the participants with WS on the basis of mental age; DS group (11
      males, 7 females) with a mean CA of 15 years 10 months (SD 5y 8mo) and a mean MA
      of 5 years 2 months (SD 8mo); and DS comparison group (10 males, 8 females) with
      a mean CA of 5 years and 1 month (SD 7mo)and a mean MA of 5 years 2 months (SD
      8mo) selected to match the DS group on the basis of mental age. They were all
      administered tests that explored visual perception (Visual Perception Test -
      Subtest 4 and Line Orientation tests), visual imagery (imaging the colour of
      objects and the tail length of well-known animals), spatial imagery (mental
      rotation of visually presented or verbally evoked objects), and WM for visual
      object and visual-spatial information. Individuals with WS exhibited specific
      difficulties in the visual-spatial, but not the visual-object, WM task. Instead,
      people with DS showed reduced performance in both tests. However, whereas the
      observed deficit in individuals with DS persisted when perceptual abilities were
      taken into account, the deficit in individuals with DS was compensated when their
      scores were adjusted for performance on perceptual tasks. These results support
      the hypothesis of a dissociation within the sketch-pad slave system in the WM
      model and reinforce the view of intellectual disability as a non-unitary
      condition.

PMID- 16417670
TI  - Visual side-effects from transdermal scopolamine (hyoscine).
AB  - Transdermal scopolamine may be used to reduce drooling in children with
      disabilities. Side-effects include dilated pupils and a reduction in the near
      point of accommodation (the closest point at which clear vision is possible). Two
      male children with epilepsy, one with spinal dysraphism (aged 7y 6mo) and one
      with cerebral palsy (aged 5y 8mo), who have undergone treatment for drooling with
      transdermal scopolamine are described. Near visual acuity was reduced, and both
      children showed dilated pupils with reduced or no response to light. These
      responses became normal on cessation of the scopolamine patch. As the effect of
      this drug may be cumulative, and many patients are unable to communicate
      difficulties, clinicians need to be aware of these possible side-effects.

PMID- 16417669
TI  - Decreased activities of mitochondrial respiratory chain complexes in non
      mitochondrial respiratory chain diseases.
AB  - The aim of this study was to illustrate the difficulties in establishing a
      diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical
      grounds in combination with intermediate activities of the MRC enzyme complexes.
      We reviewed retrospectively all medical and laboratory records of patients
      initially considered likely to have MRC disorders on clinical grounds, and
      subsequently diagnosed with other disorders (n = 20; 11 males, 9 females). Data
      were retrieved from hospital records, referral letters, and results of enzymatic
      analysis at a reference laboratory. Clinical symptoms included developmental
      delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany,
      microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss,
      muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and
      cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively.
      One or more MRC complex activities (expressed as ratios relative to citrate
      synthase and/or complex II activity) were less than 50% of control mean activity
      in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase
      complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl
      CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One
      patient had a pattern suggestive of mitochondrial proliferation. We conclude that
      intermediate results of MRC enzymes should be interpreted with caution and
      clinicians should be actively looking for other underlying diagnoses.

PMID- 16417671
TI  - Post-varicella intracranial haemorrhage in a child.
AB  - We report a case of a 7-month-old male with primary intracranial haemorrhage 2
      months after infection with varicella zoster virus (VZV). His initial clinical
      course was complicated by seizures and right hemiparesis; when last seen at 22
      months the only positive finding was of left hand preference. Although the
      literature has recently established the association of arterial ischaemic stroke
      and VZV infection, primary intracranial haemorrhage has been reported only in one
      case. The child reported here had anterior interhemispheric haemorrhage due to a
      focal arteritis of the left anterior cerebral artery. The vascular abnormality
      was transient and had radiological features compatible with either a focal
      arteritis or vasospasm as a direct result of blood surrounding the vessels. We
      postulate that direct invasion of VZV caused extensive inflammation of the vessel
      wall and aggressive tissue penetration resulting in necrotizing angiitis and
      intracranial haemorrhage. We suggest that VZV infection should be considered a
      potential risk factor for intracranial haemorrhage in children.

PMID- 16417672
TI  - Predicting additional care in young children with neurodevelopmental disability:
      a systematic literature review.
AB  - Children with developmental disabilities often show a variety of associated
      impairments that lead to a lifelong need for additional care. Careful assessment
      of these impairments is required not only for diagnostic purposes but also to
      inform the parents about the expected additional care needs in the future. We
      present a systematic review of the literature to identify instruments that
      classify the type and amount of this care for the individual child. A literature
      search was performed in the Medline database (January 1966 - June 2005) on
      instruments that classify the type and amount of expected additional care needs
      in the future. Seven standardized measurement instruments describing current
      additional care needs were identified, but none of these instruments was
      developed to provide information about the expected need for additional care in
      the future. For parents of young children with non-progressive developmental
      disorders it is essential to be informed on the expectations of required
      additional care in the future. However, comprehensive instruments providing such
      information are currently lacking and, thus, need to be developed.

PMID- 16417673
TI  - A systematic review of the self-concept of children with cerebral palsy compared
      with children without disability.
AB  - Young people with cerebral palsy (CP) are often assumed to have low self-concept,
      in other words, they do not feel good about themselves. We systematically
      searched the literature to determine whether this assumption was supported by
      empirical research. Relevant trials were identified by searching electronic
      databases, and this was supplemented by citation tracking. Of 1355 papers
      initially identified, six met the criteria for review. Results showed that
      adolescent females with CP have a lower self-concept than females without
      disability in the domains of physical appearance (d = -1.16; 95% confidence
      interval [CI] -2.06 to -0.26); social acceptance (d = -1.24; 95% CI -2.15 to 
      0.33); athletic competence (d = -0.93; 95% CI -1.79 to -0.07); and scholastic
      competence (d = -0.86; 95% CI, -1.71 to -0.01). Adolescent females with CP may be
      an at-risk group owing to their vulnerable self-concept. Clinicians may need to
      monitor and implement appropriate intervention strategies with this group. There
      was insufficient evidence to conclude that children with CP, in general, have a
      lower global self-concept compared with those without disability.

PMID- 16417675
TI  - Assessing functional differences in gross motor skills in children with cerebral
      palsy who use an ambulatory aid or orthoses: can the GMFM-88 help?

PMID- 16417677
TI  - Synthetic peptides of actin-tropomyosin binding region of troponin I and heat
      shock protein 20 modulate the relaxation process of skinned preparations of
      taenia caeci from guinea pig.
AB  - To explore the possible role of the thin filament-linked regulation of cross
      bridge cycling in living smooth muscle contraction, we studied the effects of
      TnIp and HSP20p, a synthetic peptide originating from an actin tropomyosin
      binding region of rabbit cardiac troponin I (residues 136-147; GKFKRPTLRRVR), and
      that of human heat shock protein 20 (residues 110-121; GFVAREFHRRYR) on the
      relaxation of skinned (cell membrane ilized) preparations from guinea pig taenia
      caeci. An active stress of the skinned preparations, resulting from actin-myosin
      interaction, rapidly decayed following Ca(2+) removal (relaxation). TnIp
      accelerated the initial rapid phase and slowed the following slow phase of the
      relaxation. On the other hand, HSP20p only slowed the whole process of the
      relaxation. The relaxation time courses were well fitted in a double exponential
      manner, and the double exponential decay of the stress could be explained as a
      portion of fast-detaching cross bridges not to dissociate rapidly by Ca(2+)
      removal, but to transfer to latch bridges dissociating very slowly. Our present
      results suggested that (i) TnIp and HSP20p accelerated transferring from fast
      detaching cross bridges to slow-detaching (latch) bridges, and (ii) TnIp
      accelerated dissociation of the fast-detaching cross bridges and the latch
      bridges, while HSP20p slowed dissociation the fast-detaching cross bridges. Since
      TnIp and HSP20p are thought to bind to actin and tropomyosin, but not to myosin,
      we concluded that through thin-filament-dependent mechanisms these peptides
      regulated the formation and/or deformation of latch bridges in smooth muscle. The
      thin-filament-dependent regulation might physiologically control the stress
      maintenance and relaxation in smooth muscle cells.

PMID- 16417678
TI  - Effects of attention on neuroelectric correlates of auditory stream segregation.
AB  - A general assumption underlying auditory scene analysis is that the initial
      grouping of acoustic elements is independent of attention. The effects of
      attention on auditory stream segregation were investigated by recording event
      related potentials (ERPs) while participants either attended to sound stimuli and
      indicated whether they heard one or two streams or watched a muted movie. The
      stimuli were pure-tone ABA--patterns that repeated for 10.8 sec with a stimulus
      onset asynchrony between A and B tones of 100 msec in which the A tone was fixed
      at 500 Hz, the B tone could be 500, 625, 750, or 1000 Hz, and--was a silence. In
      both listening conditions, an enhancement of the auditory-evoked response (P1-N1
      P2 and N1c) to the B tone varied with Deltaf and correlated with perception of
      streaming. The ERP from 150 to 250 msec after the beginning of the repeating ABA-
      patterns became more positive during the course of the trial and was diminished
      when participants ignored the tones, consistent with behavioral studies
      indicating that streaming takes several seconds to build up. The N1c enhancement
      and the buildup over time were larger at right than left temporal electrodes,
      suggesting a right-hemisphere dominance for stream segregation. Sources in
      Heschl's gyrus accounted for the ERP modulations related to Deltaf-based
      segregation and buildup. These findings provide evidence for two cortical
      mechanisms of streaming: automatic segregation of sounds and attention-dependent
      buildup process that integrates successive tones within streams over several
      seconds.

PMID- 16417679
TI  - Dissociating task-set selection from task-set inhibition in the prefrontal
      cortex.
AB  - Patients with focal lesions in the left (n=7) and right (n=4) prefrontal cortex
      were compared with controls (n=16) in a task-switching experiment using four
      different, simple spatial tasks. Each of these tasks involved a left-right
      decision, either regarding an arrow, the word "left" or "right," a circle
      position, or the direction of a moving line. We compared performance on trials
      that required rule switches versus rule repetitions (local switch costs) and we
      compared performance between blocks with bivalent stimuli (two dimensions
      present) and blocks with univalent stimuli (only one dimension present) to assess
      global switch costs. Patients with left prefrontal lesions, but not patients with
      right prefrontal lesions, exhibited increased costs on trials in which the
      relevant dimension switched (local switch costs), but also on no-switch trials
      with bivalent stimuli (global costs). We also assessed task-set inhibition in the
      form of the backward-inhibition effect [increased response times to recently
      abandoned tasks; Mayr, U., & Keele, S. Changing internal constraints on action:
      The role of backward inhibition. Journal of Experimental Psychology: General,
      129, 4-26, 2000]. Although left frontal patients showed normal inhibition, right
      frontal patients showed no evidence for inhibition. These results suggest a
      neurocognitive dissociation between task-set selection and inhibition.

PMID- 16417680
TI  - Neural mechanisms of cognitive control: an integrative model of stroop task
      performance and FMRI data.
AB  - We address the connection between conceptual knowledge and cognitive control
      using a neural network model. This model extends a widely held theory of
      cognitive control [Cohen, J. D., Dunbar, K., & McClelland, J. L. On the control
      of automatic processes: A parallel distributed processing model of the Stroop
      effect. Psychological Review, 97, 332-361, 1990] so that it can explain new
      empirical findings. Leveraging other computational modeling work, we hypothesize
      that representations used for task control are recruited from preexisting
      representations for categories, such as the concept of color relevant to the
      Stroop task we model here. This hypothesis allows the model to account for
      otherwise puzzling fMRI results, such as increased activity in brain regions
      processing to-be-ignored information. In addition, biologically motivated changes
      in the model's pattern of connectivity show how global competition can arise when
      inhibition is strictly local, as it seems to be in the cortex. We also discuss
      the potential for this theory to unify models of task control with other forms of
      attention.

PMID- 16417681
TI  - Intact recollection memory in high-performing older adults: ERP and behavioral
      evidence.
AB  - Numerous behavioral studies have suggested that normal aging has deleterious
      effects on episodic memory and that recollection is disproportionately impaired
      relative to familiarity-based recognition. However, there is a wide degree of
      variability in memory performance within the aging population and this
      generalization may not apply to all elderly adults. Here we investigated these
      issues by using event-related potentials (ERPs) to measure the effects of aging
      on the neural correlates of recollection and familiarity in older adults with
      recognition memory performance that was equivalent to (old-high) or lower than
      (old-low) that of young adults. Results showed that, behaviorally, old-high
      subjects exhibited intact recollection but reduced familiarity, whereas old-low
      subjects had impairments in both recollection and familiarity, relative to the
      young. Consistent with behavioral results, old-high subjects exhibited ERP
      correlates of recollection that were topographically similar to those observed in
      young subjects. However, unlike the young adults, old-high subjects did not
      demonstrate any neural correlates of familiarity-based recognition. In contrast
      to the old-high group, the old-low group exhibited neural correlates of
      recollection that were topographically distinct from those of the young. Our
      results suggest that the effects of aging on the underlying brain processes
      related to recollection and familiarity are dependent on individual memory
      performance and highlight the importance of examining performance variability in
      normal aging.

PMID- 16417682
TI  - Perceptual expertise effects are not all or none: spatially limited perceptual
      expertise for faces in a case of prosopagnosia.
AB  - We document a seemingly unique case of severe prosopagnosia, L. R., who suffered
      damage to his anterior and inferior right temporal lobe as a result of a motor
      vehicle accident. We systematically investigated each of three factors associated
      with expert face recognition: fine-level discrimination, holistic processing, and
      configural processing (Experiments 1-3). Surprisingly, L. R. shows preservation
      of all three of these processes; that is, his performance in these experiments is
      comparable to that of normal controls. However, L. R. is only able to apply these
      processes over a limited spatial extent to the fine-level detail within faces.
      Thus, when the location of a given change is unpredictable (Experiment 3), L. R.
      exhibits normal detection of features and spatial configurations only for the
      lower half of each face. Similarly, when required to divide his attention over
      multiple face features, L. R. is able to determine the identity of only a single
      feature (Experiment 4). We discuss these results in the context of forming a
      better understanding of prosopagnosia and the mechanisms used in face recognition
      and visual expertise. We conclude that these mechanisms are not "all-or-none,"
      but rather can be impaired incrementally, such that they may remain functional
      over a restricted spatial area. This conclusion is consistent with previous
      research suggesting that perceptual expertise is acquired in a spatially
      incremental manner [Gauthier, I., & Tarr, M. J. Unraveling mechanisms for expert
      object recognition: Bridging brain activity and behavior. Journal of Experimental
      Psychology: Human Perception & Performance, 28, 431-446, 2002].

PMID- 16417683
TI  - Effect of language switching on arithmetic: a bilingual FMRI study.
AB  - The role of language in performing numerical computations has been a topic of
      special interest in cognition. The "Triple Code Model" proposes the existence of
      a language-dependent verbal code involved in retrieving arithmetic facts related
      to addition and multiplication, and a language-independent analog magnitude code
      subserving tasks such as number comparison and estimation. Neuroimaging studies
      have shown dissociation between dependence of arithmetic computations involving
      exact and approximate processing on language-related circuits. However, a direct
      manipulation of language using different arithmetic tasks is necessary to assess
      the role of language in forming arithmetic representations and in solving
      problems in different languages. In the present study, 20 English-Chinese
      bilinguals were trained in two unfamiliar arithmetic tasks in one language and
      scanned using fMRI on the same problems in both languages (English and Chinese).
      For the exact "base-7 addition" task, language switching effects were found in
      the left inferior frontal gyrus (LIFG) and left inferior parietal lobule
      extending to the angular gyrus. In the approximate "percentage estimation" task,
      language switching effects were found predominantly in the bilateral posterior
      intraparietal sulcus and LIFG, slightly dorsal to the LIFG activation seen for
      the base-7 addition task. These results considerably strengthen the notion that
      exact processing relies on verbal and language-related networks, whereas
      approximate processing engages parietal circuits typically involved in magnitude
      related processing.

PMID- 16417684
TI  - Automatic drive of limb motor plasticity.
AB  - The ability to perform accurate limb movements may require learning mechanisms
      that continually tune the motor system. In the current study, we isolate a form
      of pure limb motor plasticity. Participants reached to targets that were turned
      off just after the onset of an initial eye movement, reappearing at a new
      location at the end of the reaching movement. In contrast to classical prism or
      virtual reality paradigms, our task eliminated sensory adaptation by always
      maintaining a congruency between the seen and felt limb position. We also
      minimized awareness and potential adaptation processes on the basis of volitional
      strategies by progressively increasing the size of the target perturbations. In
      this manner, our adaptation procedure mimicked conditions used to study saccadic
      adaptation. The results indicated that adaptation under these conditions led to a
      robust after-effect that generalized to a large range of movements within the
      workspace. This fully natural, nonimposed generalization of adaptation is not
      expressed in a spatial coordinate system, but more likely in a joint-centered
      coordinate space.

PMID- 16417685
TI  - Access to lexical information in language comprehension: semantics before syntax.
AB  - The recognition of a word makes available its semantic and syntactic properties.
      Using electrophysiological recordings, we investigated whether one set of these
      properties is available earlier than the other set. Dutch participants saw nouns
      on a computer screen and performed push-button responses: In one task,
      grammatical gender determined response hand (left/right) and semantic category
      determined response execution (go/no-go). In the other task, response hand
      depended on semantic category, whereas response execution depended on gender.
      During the latter task, response preparation occurred on no-go trials, as
      measured by the lateralized readiness potential: Semantic information was used
      for response preparation before gender information inhibited this process.
      Furthermore, an inhibition-related N2 effect occurred earlier for inhibition by
      semantics than for inhibition by gender. In summary, electrophysiological
      measures of both response preparation and inhibition indicated that the semantic
      word property was available earlier than the syntactic word property when
      participants read single words.

PMID- 16417686
TI  - The representation of polysemy: MEG evidence.
AB  - Most words in natural language are polysemous, that is, they can be used in more
      than one way. For example, paper can be used to refer to a substance made out of
      wood pulp or to a daily publication printed on that substance. Although virtually
      every sentence contains polysemy, there is little agreement as to how polysemy is
      represented in the mental lexicon. Do different uses of polysemous words involve
      access to a single representation or do our minds store distinct representations
      for each different sense? Here we investigated priming between senses with a
      combination of behavioral and magnetoencephalographic measures in order to test
      whether different senses of the same word involve identity or mere formal and
      semantic similarity. Our results show that polysemy effects are clearly distinct
      from similarity effects bilaterally. In the left hemisphere, sense-relatedness
      elicited shorter latencies of the M350 source, which has been hypothesized to
      index lexical activation. Concurrent activity in the right hemisphere, on the
      other hand, peaked later for sense-related than for unrelated target stimuli,
      suggesting competition between related senses. The obtained pattern of results
      supports models in which the representation of polysemy involves both
      representational identity and difference: Related senses connect to same abstract
      lexical representation, but are distinctly listed within that representation.

PMID- 16417687
TI  - An onset advantage without a preview benefit: neuropsychological evidence
      separating onset and preview effects in search.
AB  - Visual search is facilitated if half the distractors are presented as a preview
      prior to the presentation of the target and second set of distractors--the
      preview benefit [Watson, D. G., & Humphreys, G. W. Visual marking: Prioritizing
      selection for new objects by top-down attentional inhibition of old objects.
      Psychological Review, 104, 90-122, 1997]. On one account, the preview advantage
      is due to automatic capture of attention by the onsets in the second, search
      display [Donk, M., & Theeuwes, J. Visual marking beside the mark: Prioritizing
      selection by abrupt onsets. Perception & Psychophysics, 93, 891-900, 2001]. We
      provide a neuropsychological test of this assertion. We examined onset capture
      and preview benefits in search in a group of neuropsychological patients with
      unilateral parietal damage. We demonstrate a normal pattern of performance when
      patients detected targets defined by onsets relative to those defined by offsets,
      irrespective of whether the onset target fell contra- or ipsilateral to the
      lesion. In contrast, there was a normal preview benefit in search only for
      ipsilesional targets, and preview search was impaired in the contralesional
      field. The data demonstrate that the preview benefit can dissociate from the
      onset advantage in search, and that onsets remain strongly weighted for attention
      even in the contralesional field of patients with parietal lesions.

PMID- 16417688
TI  - Morphological processing in a second language: behavioral and event-related brain
      potential evidence for storage and decomposition.
AB  - This study reports the results of two behavioral and two event-related brain
      potential experiments examining the processing of inflected words in second
      language (L2) learners with Russian as their native language. Two different
      subsystems of German inflection were studied, participial inflection and noun
      plurals. For participial forms, L2 learners were found to widely generalize the 
      t suffixation rule in a nonce-word elicitation task, and in the event-related
      brain potential experiment, they showed an anterior negativity followed by a P600
      both results resembling previous findings from native speakers of German on the
      same materials. For plural formation, the L2 learners displayed different
      preference patterns for regular and irregular forms in an off-line plural
      judgment task. Regular and irregular plural forms also differed clearly with
      regard to their brain responses. Whereas overapplications of the -s plural rule
      produced a P600 component, overapplications of irregular patterns elicited an
      N400. In contrast to native speakers of German, however, the L2 learners did not
      show an anterior negativity for -s plural overapplications. Taken together, the
      results show clear dissociations between regular and irregular inflection for
      both morphological subsystems. We argue that the two processing routes posited by
      dual-mechanism models of inflection (lexical storage and morphological
      decomposition) are also employed by L2 learners.

PMID- 16417689
TI  - Prefrontal activity and diagnostic monitoring of memory retrieval: FMRI of the
      criterial recollection task.
AB  - According to the distinctiveness heuristic, subjects rely more on detailed
      recollections (and less on familiarity) when memory is tested for pictures
      relative to words, leading to reduced false recognition. If so, then neural
      regions that have been implicated in effortful postretrieval monitoring (e.g.,
      dorsolateral prefrontal cortex) might be recruited less heavily when trying to
      remember pictures. We tested this prediction with the criterial recollection
      task. Subjects studied black words, paired with either the same word in red font
      or a corresponding colored picture. Red words were repeated at study to equate
      recognition hits for red words and pictures. During fMRI scanning, alternating
      red word memory tests and picture memory tests were given, using only white words
      as test stimuli (say "yes" only if you recollect a corresponding red word or
      picture, respectively). These tests were designed so that subjects had to rely on
      memory for the criterial information. Replicating prior behavioral work, we found
      enhanced rejection of lures on the picture test compared to the red word test,
      indicating that subjects had used a distinctiveness heuristic. Critically,
      dorsolateral prefrontal activity was reduced when rejecting familiar lures on the
      picture test, relative to the red word test. These findings indicate that
      reducing false recognition via the distinctiveness heuristic is not heavily
      dependent on frontally mediated postretrieval monitoring processes.

PMID- 16417690
TI  - Prophylactic vaccines for human papillomavirus: a bright future for cervical
      cancer prevention.

PMID- 16417691
TI  - Screening for congenital hypothyroidism: the value of retesting after four weeks
      in neonates with low and very low birth weight.
AB  - OBJECTIVES: Thyroid-stimulating hormone (TSH), normally a reliable screening test
      for congenital hypothyroidism (CH), may fail to detect cases among infants who
      have low and very low birth weight. The purpose of this study was to identify
      neonates with false-negative screening results. SETTING: A province in Poland in
      which 3,854 neonates had body weight <or=2,500 g, between 1999 and 2001. METHODS:
      TSH levels in blood on filter paper were measured in all neonates between the
      third and sixth days after birth, but were repeated in low and very low birth
      weight infants after four weeks of age. RESULTS: The repeat test showed TSH
      levels >or= 10 mIU/L in 19 of the 3,854 low birth weight neonates. The final
      diagnosis in these neonates was permanent CH in two, transient CH in five,
      possible compensated CH in six and transient high TSH in six. Of the 19, 16 (84%)
      required iodine and/or thyroxine replacement therapy. CONCLUSIONS: In neonates
      with low and very low birth weight, normal TSH levels measured between the third
      and sixth day of life do not exclude thyroid dysfunction, but a repeat TSH
      measurement after the fourth week of life identifies the false-negative results.
      In our data, the prevalence of primary and secondary hypothyroidism (both
      permanent and transient) was about 0.5%.

PMID- 16417692
TI  - Neonatal screening of glucose-6-phosphate dehydrogenase deficiency in Yanbu,
      Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of glucose-6-phosphate dehydrogenase
      (G6PD) deficiency in the population tested, and to evaluate the prevalence of
      neonatal jaundice in newborns with G6PD deficiency. METHODS: Cord blood of all
      babies born between October 1996 and October 1998 at the Royal Commission Medical
      Center in Yanbu, Saudi Arabia, was screened for G6PD deficiency by fluorescent
      spot test. The results of screening of cord blood samples were reported to the
      physician in charge, and also placed on the files of the babies and their
      mothers. These babies were observed for 72 h and discharged if no jaundice
      developed. RESULTS: During this two-year period, 2,505 neonatal cord blood
      samples from 1,278 boys and 1,227 girls were screened for G6PD. There were 50
      positive results for G6PD deficiency (39 boys and 11 girls), and the prevalence
      was estimated to be around 2%. The sex-specific prevalence for boys was 3.05%,
      and for girls 0.9%. Male to female ratio was 3:1. Neonatal jaundice developed in
      six (12%) babies, five male and one female. All were treated with phototherapy
      and discharged within one week of birth. CONCLUSION: The prevalence of G6PD is
      relatively high in Yanbu. Routine neonatal screening in areas with a high
      prevalence of G6PD in Saudi Arabia is justifiable.

PMID- 16417693
TI  - Estimating mean sojourn time and screening test sensitivity in breast cancer
      mammography screening: new results.
AB  - OBJECTIVE: To assess if new screening techniques, increased use of hormone
      replacement therapy, or the transition from breast cancer screening trials to
      large scale screening programmes may influence the average time in preclinical
      screening detectable phase (mean sojourn time [MST]) or screening test
      sensitivity (STS). SETTING: Screening and interval data for 395,188 women
      participating in the Norwegian Breast Cancer Screening Programme (NBCSP).
      METHODS: Weighted non-linear least-square regression estimates using a tree step
      Markov chain model, and a sensitivity analysis of the possible impact by
      opportunistic screening between ordinary breast cancer screening rounds. RESULTS:
      MST was estimated to 6.1 (95% confidence interval [CI] 5.1-7.0) years for women
      aged 50-59 years, and 7.9 (95% CI 6.0-7.9) years for those aged 60-69 years.
      Correspondingly, STS was estimated to 58% (95% CI 52-64 %) and 73 % (67-78 %),
      respectively. Simulations revealed that opportunistic screening may give a
      moderate estimation bias towards higher MST and lower STS. Assuming a probable
      21% higher background incidence, due to increased hormone replacement therapy
      use, MST estimates decreased to 3.9 and 5.0 years for the two age groups, and STS
      increased to 75 and 85%. CONCLUSIONS: The new estimates indicate that screening
      detectable phase is longer than that found in previous mammography
      trials/programmes, but also that the sensitivity of the screening test is lower.
      Overall, the NBCSP detects more cancer cases than most previous
      trials/programmes.

PMID- 16417694
TI  - The West Midlands breast cancer screening status algorithm - methodology and use
      as an audit tool.
AB  - OBJECTIVES: To illustrate the ability of the West Midlands breast screening
      status algorithm to assign a screening status to women with malignant breast
      cancer, and its uses as a quality assurance and audit tool. METHODS: Breast
      cancers diagnosed between the introduction of the National Health Service [NHS]
      Breast Screening Programme and 31 March 2001 were obtained from the West Midlands
      Cancer Intelligence Unit (WMCIU). Screen-detected tumours were identified via
      breast screening units, and the remaining cancers were assigned to one of eight
      screening status categories. Multiple primaries and recurrences were excluded.
      RESULTS: A screening status was assigned to 14,680 women (96% of the cohort
      examined), 110 cancers were not registered at the WMCIU and the cohort included
      120 screen-detected recurrences. CONCLUSIONS: The West Midlands breast screening
      status algorithm is a robust simple tool which can be used to derive data to
      evaluate the efficacy and impact of the NHS Breast Screening Programme.

PMID- 16417695
TI  - Improving uptake of cervical cancer screening in women with prolonged history of
      non-attendance for screening: a randomized trial of enhanced invitation methods.
AB  - OBJECTIVE: To compare the effectiveness and cost-effectiveness of three methods
      of inviting women with a long history of non-attendance to undergo cervical
      screening. METHODS: Randomized controlled trial and cost-effectiveness analysis.
      In all, 1140 women were identified from routine NHS screening records as having
      no smear for at least 15 years and randomly allocated to receive a telephone call
      from a nurse, a letter from a well-known celebrity (Claire Rayner) or letter from
      the local NHS Cervical Screening Commissioner. Uptake of screening was measured
      using routine data and attributed to interventions if occurring within three
      months. Uptake was compared with a control group. Costs of carrying out the
      interventions were noted from the perspective of the NHS and cost-effectiveness,
      as cost per additional attender, calculated. RESULTS: Uptake following all
      interventions was low: telephone call (1.4, 95% confidence interval [CI] 0.38
      3.6%); celebrity letter (1.8, 95% CI 0.57-4.0%); commissioner letter (4.6, 95% CI
      2.5-7.7%); control group (1.8, 95% CI 0.57-4.0%). There were no significant
      differences between groups. Telephone intervention was not possible in a quarter
      of women whose numbers were unlisted. Telephone intervention was the most
      expensive and least effective of the interventions. The commissioner letter
      yielded an additional attender within three months at an incremental cost of
      23.21 pounds compared with taking no action. CONCLUSIONS: Neither a telephone
      call from a nurse nor a letter from a celebrity to encourage attendance for
      cervical screening were effective or cost-effective in women with a prolonged
      history of non-participation in the screening programme. A letter from the local
      cervical screening programme commissioner resulted in a small, non-significant
      increase in uptake. The low cost and ease of implementation of this intervention
      supports further research into its use in routine practice.

PMID- 16417696
TI  - A study of Pap test history and histologically determined cervical cancer in NSW
      women, 1997-2003.
AB  - OBJECTIVES: To determine the risk of a histological diagnosis of cervical cancer
      following a given Pap test result and for a given history of Pap test results in
      a screened population across the full spectrum of possible cytological results.
      METHODS: All the Pap screening results held on the New South Wales Pap Test
      Register for 1997-2003 (five million tests for 1.87 million women) were analysed
      using Cox proportional hazards regression to estimate the odds of having a
      histologically determined cervical cancer for a given Pap test result and test
      result history. The hazard ratios of having cervical cancer in relation to Pap
      test result histories were estimated: (i) in regard only to the last Pap test
      result adjusting for age, frequency of Pap testing and proportion of high grade
      (>or=cervical intraepithelial neoplasia 2 [CIN2]) abnormalities found in a
      woman's total recorded test result history; and (ii) with regard to the last Pap
      test result against the highest grade of cytological abnormality found prior to
      the last Pap test result. The hazard ratios are for a cancer diagnosis occurring
      before the next Pap test and were adjusted for age, quintile of socioeconomic
      status of residence, frequency of past Pap testing and proportion of high-grade
      abnormalities detected in each woman's prior Pap test history. The adjusted
      hazard ratios were then applied to the tabulated proportions of referent women
      with negative cytology in each broad age group, and for all women, to estimate
      the '1 in n' odds of being diagnosed histologically with cervical cancer for a
      given last Pap test result, and by a given last Pap test result for various prior
      Pap test result histories. RESULTS: After adjusting for age, socioeconomic
      status, frequency of previous Pap testing and proportion of past high-grade
      screen-detected abnormalities, the adjusted hazard ratio of having a subsequent
      cervical cancer diagnosis for women with a negative Pap test result was 1 in
      5,546, compared with 1 in 833 for a low-grade epithelial abnormality (atypia,
      CIN1), 1 in 56 for a high-grade epithelial abnormality and 1 in seven for a
      cytological prediction of cervical cancer. These odds estimates were
      significantly modified by age and by the highest Pap test result prior to the
      most recent Pap test result: the higher the age and, less consistently, the
      higher the previous highest Pap test result for a given last Pap test result, the
      shorter the odds of having a subsequent histological diagnosis of cervical
      cancer. CONCLUSIONS: The results presented here will enable clinicians to inform
      their patients of their chances of being diagnosed with cervical cancer for a
      given Pap test result, and for some combinations of the last Pap test result and
      highest recorded prior Pap test result.

PMID- 16417697
TI  - The efficacy of combining several risk factors as a screening test.
AB  - OBJECTIVE: To determine the quantitative effect on overall screening performance
      (detection rate for a given false-positive rate) of using several moderately
      strong, independent risk factors in combination as screening markers. SETTING:
      Theoretical statistical analysis. METHODS: For the purposes of this analysis, it
      was assumed that all risk factors were independent, had Gaussian distributions
      with the same standard deviation in affected and unaffected individuals and had
      the same screening performance. We determined the overall screening performance
      associated with using an increasing number of risk factors together, with each
      risk factor having a detection rate of 10%, 15% or 20% for a 5% false-positive
      rate. The overall screening performance was estimated as the detection rate for a
      5% false-positive rate. RESULTS: Combining the risk factors increased the
      screening performance, but the gain in detection at a constant false-positive
      rate was relatively modest and diminished with the addition of each risk factor.
      Combining three risk factors, each with a 15% detection rate for a 5% false
      positive rate, yields a 28% detection rate. Combining five risk factors increases
      the detection rate to 39%. If the individual risk factors have a detection rate
      of 10% for a 5% false-positive rate, it would require combining about 15 such
      risk factors to achieve a comparable overall detection rate (41%). CONCLUSION: It
      is intuitively thought that combining moderately strong risk factors can
      substantially improve screening performance. For example, most cardiovascular
      risk factors that may be used in screening for ischaemic heart disease events,
      such as serum cholesterol and blood pressure, have a relatively modest screening
      performance (about 15% detection rate for a 5% false-positive rate). It would
      require the combination of about 15 or 20 such risk factors to achieve detection
      rates of about 80% for a 5% false-positive rate. This is impractical, given the
      risk factors so far discovered, because there are too few risk factors and their
      associations with disease are too weak.

PMID- 16417698
TI  - Corrections to maternal age-specific live birth prevalence of Down's syndrome.

PMID- 16417699
TI  - Trisomy 18 fetuses with cystic hygroma linked to positive maternal serum Down's
      syndrome Triple test screening result.

PMID- 16417701
TI  - UK Health Technology Assessment (HTA) Programme.

PMID- 16417700
TI  - An evaluation of a social marketing campaign to reduce the number of London women
      who have never been screened for cervical cancer.

PMID- 16417702
TI  - The Nord-Trondelag Norway Audiometric Survey 1996-98: unscreened thresholds and
      prevalence of hearing impairment for adults > 20 years.
AB  - As supplement to a general health screening examination (HUNT-II), we conducted a
      puretone audiometry study in 1996-98 on adults (>20 years) in 17 of 23
      municipalities in Nord-Trondelag, Norway, including questionnaires on
      occupational and leisure noise exposure, medical history, and symptoms of hearing
      impairment. The study aims to contribute to updated normative hearing thresholds
      for age and gender, while evaluating the effects of noise exposure, medical
      history, and familial or genetic influences on hearing. This paper presents the
      unscreened hearing threshold data and prevalence of hearing impairment for
      different age groups and by gender. Valid audiometric data were collected from
      62% (n=50,723) of 82,141 unscreened invited subjects (age-range 20-101 years,
      mean=50.2 years, SD=17.0 years). Two ambulant audiometric teams each conducted 5
      parallel self-administered, pure-tone hearing threshold examinations with the
      standard test frequencies 0.25-0.5-1-2-3-4-6-8 kHz (manual procedure when
      needed). Tracking audiometers were used in dismountable booths with in-booth
      noise levels well within ISO criteria, except being at the criterion around 200
      Hz. The data were electronically transferred to a personal computer. Test-retest
      correlations for 99 randomly drawn subjects examined twice were high. The mean
      thresholds recorded were some dB elevated from "audiometric zero" even for age
      group 20-24 years. As also found in other studies, this might indicate too
      restrictive audiometric reference thresholds. Males had slightly better hearing <
      or =0.5 kHz for all age groups. Mean thresholds were poorer in males > or = 30
      years from > or =2 kHz, with maximal gender differences of approximately 20 dB at
      3-4 kHz for subjects aged 55-74 years. Weighted prevalence data averaged over 0.5
      1-2-4 kHz showed hearing impairment >25 dB hearing threshold level of 18.8%
      (better ear) and 27.2% (worse ear) for the total population--for males 22.2% and
      32.0%, for females 15.9% and 23.0%, respectively. Mean hearing loss > or =10 dB
      at 6 kHz registered for both genders even in age groups 20-24 years may be partly
      due to calibration artefacts, but might possibly also reflect noise-related socio
      acusis.

PMID- 16417703
TI  - Combined effects of noise and gentamicin on hearing in the guinea pig.
AB  - The last ten years, the use of gentamicin has increased due to antibiotic
      resistance among bacterial pathogens. One of the side effects of gentamicin is
      its toxicity on hearing. Several authors had even pointed out synergistic effects
      of gentamicin and noise on hearing. It was therefore reasonable to think that the
      damaging effects of noise could be emphasized by a gentamicin treatment of the
      subjects. In order to test the applicability of the Leq8h for estimating the
      hazard of noise on animals treated with a non-ototoxic dose of gentamicin (40
      mg/kg for 8 days), two experiments were carried out with guinea pigs. The animals
      were exposed to octave band noises centred at 8 kHz and treated with gentamicin
      either simultaneously or sequentially with regard to the noise exposure. Two
      noise exposures having different acoustic energy, respectively Leq8h = 85 dB and
      98.8 dB SPL, were tested. The auditory function of the guinea pigs was tested by
      recording auditory-evoked potentials. The electrophysiological findings were
      completed by histological data. The gentamicin treatment tested in the current
      studies did not cause any auditory permanent threshold shift neither cochlear
      disruptions, although the treatment could be considered as approximately ten
      times the therapeutic dose used in human. The auditory deficit induced by the
      mixed exposures to noise and gentamicin did not worsen the noise effect alone in
      our experimental conditions. As a result, the European value recommended for
      noise exposure (Leq8h=85 dB) seems to be robust enough to protect gentamicin
      treated workers.

PMID- 16417704
TI  - Confounding or aggravating factors in noise-induced health effects: air
      pollutants and other stressors.
AB  - Different scientific groups have studied and continue to study the health impacts
      of physical and chemical agents in the environment. In most cases, every study
      group has considered the health effect as being solely due to the air
      pollutant(s) under investigation, for example air pollution without due regard
      for the simultaneous presence of noise pollution whereas both have an impact on
      the cardiovascular system. Or in the case of noise studies the contribution of
      solvent, asphyxiant or metal exposures has not been considered, which can have an
      impact on hearing impairment. One can, therefore, question the stringency of the
      available evidence of epidemiological studies in both fields to warrant the
      consideration of air pollutants as confounding or aggravating factors in studies
      of specific effects due to noise (and vice versa). In this paper we weigh the
      existing evidence on the association of noise and air pollutant exposure and
      associated health impacts. In forthcoming publications, the authors will consider
      the influence of other factors, which can confound noise studies but are
      currently not included in the analysis.

PMID- 16417705
TI  - Hearing protector performance and standard deviation.
AB  - The attenuation performance of a hearing protector is used to estimate the
      protected exposure level of the user. The aim is to reduce the exposed level to
      an acceptable value. Users should expect the attenuation to fall within a
      reasonable range of values around a norm. However, an analysis of extensive test
      data indicates that there is a negative relationship between attenuation
      performance and the standard deviation. This result is deduced using a variation
      in the method of calculating a single number rating of attenuation that is more
      amenable to drawing statistical inferences. As performance is typically specified
      as a function of the mean attenuation minus one or two standard deviations from
      the mean to ensure that greater than 50% of the wearer population are well
      protected, the implication of increasing standard deviation with decreasing
      attenuation found in this study means that a significant number of users are, in
      fact, experiencing over-protection. These users may be disinclined to use their
      hearing protectors because of an increased feeling of acoustic isolation. This
      problem is exacerbated in areas with lower noise levels.

PMID- 16417706
TI  - The first century.

PMID- 16417707
TI  - The efficacies of artesunate-sulfadoxine-pyrimethamine and artemether
      lumefantrine in the treatment of uncomplicated, Plasmodium falciparum malaria, in
      an area of low transmission in central Sudan.
AB  - In an efficacy trial of artemisinin-based combination treatments (ACT) in central
      Sudan, cases of uncomplicated, Plasmodium falciparum malaria were given
      artesunate-sulfadoxine-pyrimethamine (ASP) or artemether-lumefantrine (AL) as
      first-line treatment. On enrolment, the 71 patients given ASP were similar to the
      72 given AL, apart from having generally lower parasitaemias (geometric mean
      counts of 4893 nu. 10,215 asexual parasites/microl) and having a lower mean age
      (15 nu. 23 years). Each patient was treated on days 0, 1 and 2, and all 137 who
      completed follow-up without further, unscheduled treatment were found
      aparasitaemic and afebrile from day 2 until the last follow-up, on day 28. No
      moderate or severe adverse side-effects, clinical failures or parasitological
      failures were observed among these 137 patients. ACT therefore appear both
      efficacious and safe for the treatment of uncomplicated malaria in central Sudan.

PMID- 16417708
TI  - Monitoring of the therapeutic efficacy of chloroquine for the treatment of
      uncomplicated, Plasmodium falciparum malaria in Iran.
AB  - Between 2002 and 2004, the standardized 28-day protocol recently developed by the
      World Health Organization was used to explore the efficacy of chloroquine, in the
      treatment of uncomplicated, Plasmodium falciparum malaria, in five sentinel sites
      in southern Iran. All but 14 of the 158 patients enrolled (128, 28 and two from
      the provinces of Sistan-Baluchestan, Hormozgan and Kerman, respectively) were
      successfully followed-up. The overall frequency of treatment failure by day 28
      was 78.5%, with 17.4% of the patients being classed as early treatment failures,
      34.7% as late clinical failures, and 26.4% as late parasitological failures.
      There appeared to be no significant change in the frequency of treatment failure
      between the 2002-2003 and 2003-2004 transmission seasons, nor any significant
      between-site variation in the efficacy of chloroquine. Given these observations,
      the replacement of chloroquine, as the first-line drug for the treatment of
      uncomplicated, P. falciparum malaria in Iran, was inevitable. Artesunate
      sulfadoxine-pyrimethamine is now the recommended first-line treatment, with
      artemether-lumefantrine used for second-line treatment. The efficacies of these
      combination therapies are currently being evaluated and monitored.

PMID- 16417709
TI  - Fractions of an antimalarial neem-leaf extract have activities superior to
      chloroquine, and are gametocytocidal.
AB  - The antimalarial activities of two fractions (IRDN-A and IRDN-B) of an extract
      from the leaves of the neem tree (Azadirachta indica) were compared with those of
      chloroquine, in in-vitro assays against Plasmodium falciparum. The asexual stages
      of a chloroquine-sensitive clone (ITG2F6) and a chloroquine-resistant isolate
      (W2) and the gametocytes of the NF 54 (BD-7) isolate of P. falciparum were used
      as the drug targets. Activity against the asexual stages was generally evaluated
      as the concentrations inhibiting the parasitaemias recorded in the control
      cultures, after an incubation of 48-72 h, by 50% (IC50) or 100% (IC100). For the
      ITG2F6 strain, the IC50 and IC100 (in microg/ml) were, respectively, 10(-5) and
      10(-4) for IRDN-A, 10(-3) and 10(-2) for IRDN-B, and 10(-2) and 1.0 for
      chloroquine. The corresponding values for the W2 strain were 10(-5) and 1.0 for
      IRDN-A, and 10.0 and >100 for chloroquine (even at 100 microg/ml, chloroquine
      only inhibited the parasitaemia by 85%). Each of the two neem-leaf fractions
      lysed 50% and 100% of developing gametocytes, at 10(-3) and 1.0 microg/ml,
      respectively; and 50% and 100% of mature gametocytes at 10(-3) and 10(2)
      microg/ml, respectively. If they are found safe and effective in vivo, the neem
      leaf fractions may form the basis of new antimalarial drugs that not only cure
      chloroquine-sensitive and chloroquine-resistant malaria but also markedly reduce
      transmission.

PMID- 16417711
TI  - Possible mechanisms of action of the compounds injected intralesionally in the
      treatment of cutaneous leishmaniasis, in addition to their direct effects on the
      parasites.
AB  - By injecting uninfected rabbits intradermally with one of the test compounds or
      the isotonic saline (0.9% NaCl) used as a control, the possible mechanisms of the
      indirect action of some drugs used intralesionally in the treatment of human
      cutaneous leishmaniasis [sodium stibogluconate, 2% zinc sulphate, and hypertonic
      (7% NaCL) saline] were explored. The 24 injected rabbits (six for the control and
      six for each test compound) were followed up for 30 days, both macroscopically,
      with checks for erythema and increases in skin thickness, and microscopically,
      with the histopathological examination of sections of biopsies from the injection
      sites. Although the microscopy revealed inflammatory-cell infiltration, beginning
      with eosinophils, followed by lymphocytes and finally by the proliferation of
      fibroblasts, at all of the injection sites, these changes were most intense with
      the sodium stibogluconate and 2% zinc sulphate, less marked with the hypertonic
      saline, and minimal and relatively short-lived with the isotonic saline.
      Presumably as a result of their metal content, sodium stibogluconate and zinc
      sulphate each probably induce tissue damage and, subsequently, severe
      inflammatory changes. The antileishmanial activity of hypertonic saline, however,
      may be entirely attributable to its osmotic effects.

PMID- 16417710
TI  - The flow-cytometry-based evaluation of cellular immunity in cases of cutaneous
      leishmaniasis and healthy controls from the endemic area in southern Israel.
AB  - Only limited data are available on the early immunological events associated with
      human cutaneous leishmaniasis (CL). In this study, peripheral-blood mononuclear
      cells were obtained from 66 individuals (34 patients with cutaneous lesions and
      32 apparently healthy controls) who had each spent no more than 3 months in the
      endemic region of Qetzioth, in southern Israel. These cells' responses to
      Leishmania major antigen were then explored, by the flow-cytometry-based
      evaluation of blast transformation (BT). The lymphocytes from 17 (50%) of the
      patients but only one (3%) of the controls displayed BT. When, in an ELISA, most
      (52) of the subjects were checked for anti-L. major antibodies, none of the 22
      controls investigated but 19 (63%) of the 30 patients were found seropositive.
      Although 14 (47%) of the 30 patients who were checked for antibodies were BT
      positive, the seropositive patients were not significantly more or less likely to
      be BT-positive than the seronegative patients (P<0.919). These data indicate
      that, in CL, the hosts' cellular and humoral responses develop independently
      within the first 3 months post-infection, but further investigation is required
      to confirm this hypothesis.

PMID- 16417712
TI  - Evaluation of ELISA and dot blots for the serodiagnosis of neurocysticercosis, in
      children found to have single or multiple enhancing lesions in computerized
      tomographic scans of the brain.
AB  - Although human neurocysticercosis (NCC) is being increasingly recognized in
      children, diagnosis of the disease can be difficult, and the 'gold standard'
      criteria that indicate an unambiguous case have still to be established. In the
      present study, the performances of an ELISA and dot-blot assay, for the detection
      of antibodies against antigens from larval Taenia solium, were investigated and
      compared, using sera, from children aged 5-12 years, that were diluted to at
      least 1:400. Eighty of the subjects (20 aged 5-<8 years and 60 older children)
      each had the signs and symptoms of NCC, including one brain lesion (N=69) or
      multiple brain lesions (N=11) that were visible by computed tomography. Another
      100 sera, from children who had tubercular meningitis (N=20) or a parasitic
      disease other than taeniasis/cysticercosis (N=20) or, apart from a minor
      respiratory-tract infection, appeared healthy (N=60), were also investigated.
      Most (86%) of the cases of NCC had presented with focal seizures. Analysis of
      antibody response indicated that the optimum threshold titres for seropositivity
      were 1:800 for the ELISA and 1:6400 for the dot-blot assays. When used with these
      thresholds, the ELISA gave a sensitivity, specificity, positive and negative
      predictive values and diagnostic efficacy of 89%, 81%, 79%, 90%, 85%,
      respectively. The corresponding values for the dot-blot assay were similar, at
      89%, 73%, 72.5%, 89%, 82%, respectively. Both assays were more sensitive, in the
      detection of the specific antibody response, when used among the paediatric cases
      of NCC who had multiple brain lesions (100%) than when used among the single
      lesion cases (87%). As the ELISA gave higher specificity and diagnostic efficacy
      than the dot-blot assay, it should be considered the better method for the
      serological confirmation of NCC in children.

PMID- 16417713
TI  - Absence of cervical schistosomiasis among women from two areas of north-eastern
      Brazil with endemic Schistosoma mansoni.
AB  - Genital manifestations in schistosomiasis haematobium are common and are
      associated with considerable morbidity. Although Schistosoma mansoni may also
      cause genital disease, the frequency of this complication is not known. Cervical
      biopsies (N=401) and Pap smears (N=981) were therefore collected from women
      living in two S. mansoni-endemic areas (in the states of Alagoas and Ceara, in
      north-eastern Brazil). The women were screened for the presence of sexually
      transmitted diseases and for the presence, in their cervical smears and/or
      biopsies, of S. mansoni eggs. Attempts at schistosomiasis control, which began in
      both study areas in 1977, have led to generally low intensities of infection (<30
      eggs/g faeces in 99% of infections) and community prevalences of infection that
      range between 1% and 52%. As no schistosome ova were detected in any of the
      biopsies or smears, it appears that the risk, among women, of genital
      manifestations of S. mansoni infection is small in areas where the parasite load
      in the population is low (as the result of interventions to control intestinal
      schistosomiasis).

PMID- 16417714
TI  - Carriage by the German cockroach (Blattella germanica) of multiple-antibiotic
      resistant bacteria that are potentially pathogenic to humans, in hospitals and
      households in Tripoli, Libya.
AB  - Using standard bacteriological procedures, 403 cockroaches (Blattella germanica)
      collected in Tripoli, from hospitals or the households surrounding the hospitals,
      were examined for bacteria that are potentially pathogenic to humans. Almost all
      of the cockroaches (96.1% of the 253 from hospitals and 98.7% of the 150 from
      households) were found to be carrying potentially pathogenic bacteria, with
      similar mean burdens of 3.2 x 10(5) colony-forming units (cfu) (range=0-1.4 x
      10(7)) for each hospital cockroach and 1.9 x 10(5) cfu (range=0-3.1 x 10(6)) for
      each household cockroach (P>0.05). Overall, 27 and 25 species of potential
      pathogen were isolated from the hospital and household cockroaches, respectively,
      with Klebsiella, Enterobacter, Serratia and Streptococcus predominant. Carriage
      of species of Serratia was significantly more common among the hospital
      cockroaches than among the household cockroaches, whereas carriage of Klebsiella,
      Enterobacter, Citrobacter and Aeromonas was significantly more common among the
      household cockroaches than among the hospital. Multiple resistance, to at least
      six different antibiotics, was more commonly observed among the enteric bacteria
      isolated from the hospital cockroaches than among those recovered from the
      household cockroaches. Overall, >30% of the isolates of Enterobacteria recovered
      were each resistant to at least four antimicrobial agents, and 95% of the
      Pseudomonas isolates were each resistant to at least eight such agents.
      Cockroaches may play an important role in the spread of multiple-antibiotic
      resistant, bacterial pathogens within the hospitals and surrounding communities
      of Tripoli and other, similar cities. The local health and environmental
      authorities need to be encouraged to treat B. germanica infestations seriously
      and to control them quickly and effectively.

PMID- 16417715
TI  - Phlebotomus (Paraphlebotomus) alexandri: a probable vector of Leishmania infantum
      in Iran.
AB  - The incidence of human visceral leishmaniasis (VL) caused by Leishmania infantum,
      which is endemic in several parts of Iran, has recently increased in the Nourabad
      Mamassani district of Fars province, in the south of the country. Between 2003
      and 2005, 12,688 sandflies were caught in this focus, using CDC miniature light
      traps, sticky traps and aspirators, in an attempt to identify the main vector of
      L. infantum. When 120 of the parous, female Phlebotomus (Paraphlebotomus)
      alexandri caught were individually checked for Leishmania infection, in an assay
      based on PCR and kinetoplast minicircle primers (LINR4 and LIN17), five (4.2%) of
      the flies were found to be infected with L. infantum. Thirty-nine (32.5%) of the
      120 blood-fed Ph. alexandri checked in an ELISA were found positive for human
      blood. Since Ph. alexandri was the third-most common species caught (representing
      over 17% of the total catch), was clearly anthropophilic, and was not
      infrequently infected with L. infantum, it is probably an important vector in the
      Nourabad-Mamassani focus. Although other sandfly species have been found
      naturally infected with promastigotes in Iran, Ph. alexandri is the first that
      has been proven to harbour L. infantum in the country.

PMID- 16417716
TI  - Antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract
      of Laportea ovalifolia (Urticaceae), measured in rats with alloxan-induced
      diabetes.
AB  - A decoction of the leaves of Laportea ovalifolia is widely used in Cameroon for
      the treatment of several illnesses, including diabetes mellitus. The antidiabetic
      and hypolipidaemic effects of a methanol/methylene-chloride extract of the aerial
      parts of L. ovalifolia have now been investigated, in normal rats and rats with
      diabetes induced by the intraperitoneal injection of alloxan (at 150 mg/kg
      bodyweight). In the diabetic rats, 2 weeks of daily, intragastric treatment with
      the L. ovalifolia extract not only produced a significant reduction in the
      fasting serum glucose concentrations but also lowered the serum concentrations of
      total cholesterol, triglycerides, and low-density-lipoprotein cholesterol,
      lowered the ratio of total cholesterol to high-density-lipoprotein (HDL)
      cholesterol, and increased the serum concentration of HDL cholesterol. At least
      in rats with alloxan-induced diabetes, the methanol/methylene-chloride extract of
      L. ovalifolia therefore appears to possess antidiabetic and hypolipidaemic
      properties.

PMID- 16417717
TI  - The schistosome intermediate host, Bulinus nyassanus, is a 'preferred' food for
      the cichlid fish, Trematocranus placodon, at Cape Maclear, Lake Malawi.
AB  - Over the last decade, transmission of the schistosome parasites of humans has
      increased in parts of Lake Malawi, possibly because over-fishing has led to a
      decline in the numbers of molluscivorous fish. The stomach contents of 51 wild
      caught Trematocranus placodon from the Cape Maclear area of Lake Malawi have now
      been investigated and compared with the field abundance of snail species at two
      sites, close to where the fish were caught. The snails found in the fish stomachs
      were identified to genus or species on the basis of their shell fragments and/or
      opercula. The sizes of the prosobranchs consumed by the T. placodon were
      determined from their operculum sizes whereas the Bulinus nyassanus ingested by
      the fish were categorized as small (<4 mm) or large (> or =4 mm) on the basis of
      their shell fragments. The proportion of the Bu. nyassanus ingested that were
      categorized as large increased with fish size. Furthermore, the relative
      abundance of Bu. nyassanus in the guts of the fish was considerably higher than
      in the field, indicating that the T. placodon had a 'preference' for Bu.
      nyassanus over the Melanoides species that dominated the snail fauna. Small
      specimens of Bellamya species were also consumed in a greater proportion than
      found in field.

PMID- 16417718
TI  - Microculture for the isolation of Leishmania, modified to increase efficacy: a
      follow-up to a previous study.

PMID- 16417721
TI  - The Italian law on assisted reproduction: a view from Spain.
AB  - Despite the pessimistic concerns about the outcome of assisted reproduction in
      Italy after the application of the new law, initial reports show similar
      pregnancy rates. However, with increasing numbers, the deleterious effect of such
      a restrictive law will show up. Moreover, it may seriously affect the scientific
      production of Italian groups, which may be forced to migrate to other countries
      to maintain their independence and scientific freedom.

PMID- 16417722
TI  - Effect of Italian referendum on global IVF: a comment from Turkey.
AB  - The recent referendum results on the Italian law on assisted conception have
      created an intense debate among IVF researchers. Since controversy can exist
      regarding scientific, ethical and moral issues, as well as how things can be
      perceived differently in different countries, and as the authors practise IVF in
      a secular country where approximately 95% of the population is Muslim, this paper
      aims to discuss and comment on this issue as a response to the article by Manna
      and Nardo.

PMID- 16417723
TI  - To add or not to add LH: consideration of LH concentration changes in individual
      patients.
AB  - The availability of recombinant FSH and LH opens an opportunity to individualize
      ovarian stimulation. While the need for FSH is universal, a question remains
      whether exogenous LH is beneficial. Previous research on adding LH to an
      unselected group of patients failed to demonstrate any advantage. Indeed, it may
      seem presumptuous to expect that all patients will respond in the same manner.
      Recent studies hint that LH supplementation should be individualized. These
      studies indirectly suggest that the changes in LH concentration may be more
      important than the concentration per se. The growing follicle, and particularly
      oestradiol biosynthesis, may be sensitive to decreases in LH concentrations. The
      challenge is to identify the patient whose LH will drop during stimulation. This
      individualized approach will assure that supplemented LH will only be given to
      those who need it.

PMID- 16417724
TI  - Genetic testing of embryos: a critical need for data.
AB  - Preimplantation genetic diagnosis (PGD), the genetic testing of embryos developed
      through IVF is one of the fastest growing techniques in reproductive medicine and
      IVF. Some suggest that PGD will become part of every IVF cycle in the future. The
      growing popularity of PGD has highlighted the fact that there are no
      comprehensive data available about the use of PGD, its accuracy, or the health
      outcomes of babies born following PGD. For patients, practitioners, and
      policymakers alike, such information is critical. To address the gaps in
      knowledge, a working group of the leading experts in the development and practice
      of PGD and IVF has begun to design a database to collect information about PGD as
      practised in the United States.

PMID- 16417726
TI  - Non-invasive screening and rapid QF-PCR assay can greatly reduce the need for
      conventional cytogenetic analyses in prenatal diagnosis.
AB  - In 2004, the UK National Screening Committee suggested that rapid screening
      tests, such as fluorescence in-situ hybridization (FISH) and/or quantitative
      fluorescence PCR (QF-PCR), should replace prenatal diagnosis of Down syndrome
      performed by conventional karyotyping. However, doubts have been expressed that
      replacement of conventional cytogenetic investigations would result in a
      substantial number of infants affected by preventable handicaps. Based on a brief
      analysis of 28,000 prenatal tests performed in genetic units, this paper
      discusses the advantages of using QF-PCR. All normal fetuses were correctly
      diagnosed without false positive results and approximately 93% major chromosome
      disorders were detected by the molecular approach. The need for cytogenetic tests
      was thus greatly reduced, since pregnancy can be terminated, if necessary,
      without the need to confirm the results. A careful combination of accurately
      performed non-invasive ultrasound and maternal blood tests, eventually followed
      by QF-PCR, should reduce the need for conventional chromosome analyses.

PMID- 16417727
TI  - Vaginal lactobacilli, probiotics, and IVF.
AB  - Perturbation of the normal lactobacilli-dominated vaginal microflora is
      associated with reproductive failure and adverse pregnancy outcomes, ranging from
      early pregnancy loss to late miscarriage and preterm birth. As high rates of
      bacterial vaginosis are observed with IVF patients, abnormal vaginal microflora
      presumably explain, at least to some extent, reproductive failure as well as the
      increased risk of adverse pregnancy outcome seen in these patients. Accordingly,
      there may be a window of opportunity for improving IVF success rates and
      outcomes. At present, a screen-and-treat procedure to restore the normal vaginal
      microflora is not a routine part of the infertility work-up and treatment. While
      Gram staining of vaginal smears would offer an inexpensive and validated means
      for screening and diagnosis, probiotics that contain live lactobacilli capable of
      re-colonizing the vagina may offer an elegant and safe choice of treatment.
      Carefully designed trials using well characterized probiotic strains and
      treatment regimens are still required to evaluate the effect of probiotics on IVF
      embryo transfer pregnancy rates.

PMID- 16417728
TI  - International egg-sharing to provide donor oocytes for clinical assisted
      reproduction and derivation of nuclear transfer stem cells.
AB  - Recent advances in nuclear transfer technology for derivation of patient-specific
      stem cells have opened up new avenues of therapy for various human diseases.
      However, a major bottleneck is the severe shortage of human donor oocytes. Egg
      sharing in return for subsidized fertility treatment has been suggested as an
      ethically justifiable and practical solution to ease the shortage of donor
      oocytes both for derivation of nuclear transfer stem cells and assisted
      reproduction. However, it is envisioned that many patients would be more
      comfortable with their supernumerary oocytes going into derivation of nuclear
      transfer stem cells, rather than having another potential anonymous offspring in
      assisted reproduction. Nevertheless in more economically developed countries,
      fertility treatment is easily affordable to a large segment of the population,
      which reduces the pool of available egg-sharers. In less affluent countries,
      fertility treatment is often beyond the financial resources of most sub-fertile
      couples. Hence, a possible solution may be to allow egg-sharing across
      international borders. Potential egg-sharers would come from less economically
      developed countries that are more in need of financial subsidies for sub-fertile
      couples seeking clinically assisted conception. This is ethically justifiable
      because it makes fertility treatment affordable to childless couples from poorer
      countries, while at the same time easing the shortage of donor oocytes in more
      affluent countries.

PMID- 16417730
TI  - Reproductive outcome using a GnRH antagonist (cetrorelix) for luteolysis and
      follicular synchronization in poor responder IVF/ICSI patients treated with a
      flexible GnRH antagonist protocol.
AB  - To investigate the possible beneficial effect of a new stimulation protocol
      (termed 'CRASH') on the outcome of poor responder patients, a multicentre,
      prospective longitudinal study including a total of 36 women undergoing 72
      IVF/intracytoplasmic sperm injection (ICSI) cycles with patients serving as their
      own controls, was conducted. A poor responder patient was defined as a patient
      with four or fewer oocytes extracted from five or fewer follicles and with a
      total FSH consumption exceeding 2000 IU in a preceding long agonist down
      regulation protocol. The CRASH protocol included 3 mg of the gonadotrophin
      releasing hormone (GnRH) antagonist cetrorelix given in the late luteal phase on
      cycle day 23. Stimulation with recombinant human FSH (rhFSH) started on cycle day
      2, followed by a flexible GnRH antagonist protocol. The results showed
      significantly more follicles (5.4 versus 3.5), oocytes (4.3 versus 2.4) and
      transferable embryos (1.8 versus 0.8) with the CRASH protocol as compared with
      the preceding long protocol (P < 0.005 in all cases). The implantation rate and
      pregnancy rate per transfer was 18.4 and 38.5% respectively, approaching the
      clinical outcome of normal responder patients. The CRASH protocol thus may
      constitute an attractive alternative to conventional protocols for low responder
      patients, improving their clinical outcome.

PMID- 16417731
TI  - Controlled natural cycle IVF with antagonist use and blastocyst transfer.
AB  - A method of controlled natural cycle IVF (CONCIVF) was sought to provide simpler
      and shorter treatment without the risks of ovarian hyperstimulation syndrome and
      multiple pregnancies. A total of 138 couples with normal ovulation and normal
      sperm parameters, in whom the women were <40 years old, were the candidates for
      this study. Gonadotrophin-releasing hormone antagonist was used before human
      chorionic gonadotrophin (HCG) administration if LH increased to a concentration
      of 10 mIU/ml before HCG injection. Treatment was initiated at > or =16 mm
      follicular growth and at oestradiol concentrations > or =400 pmol/l with 5000 IU
      HCG induction. All the embryos were cultured to the blastocyst stage and
      transferred only if they reached early or advanced blastulation. A total of 126
      patients underwent oocyte retrieval. In 102 cases, one oocyte was retrieved; 95%
      of the oocytes fertilized, 99% cleaved and 47.9% achieved the blastocyst stage.
      The implantation rate per blastocyst transfer was 53.3% and the live-birth rate
      per embryo transfer was 40%. Therefore, CONCIVF with blastocyst transfer gives
      acceptable blastocyst development and implantation rates without the long- or
      short-term side effects of ovulation induction.

PMID- 16417732
TI  - Influence of oral contraceptive pills on phenotype expression in women with
      polycystic ovary syndrome.
AB  - Polycystic ovarian syndrome (PCOS) is characterized by a heterogeneous phenotype
      including chronic anovulation, hyperandrogenism and polycystic ovaries. The use
      of oral contraceptive pills (OCP) alters features characteristic for the
      syndrome. In the present study, PCOS features were compared between women using
      or not using OCP at the time of the study. One hundred and one women diagnosed
      with normogonadotrophic anovulatory infertility were included. A total of 81
      (80%) women were diagnosed with PCOS (revised 2003 criteria). From these women, a
      total of 54 did not use OCP, whereas 27 women did. Corrected for age, women
      taking OCP had increased serum concentrations of sex hormone-binding globulin (P
      < 0.001). Serum concentrations of testosterone (P = 0.04) and androstenedione (P
      = 0.01) were decreased. These differences resulted in a decreased free androgen
      index for women currently taking OCP compared with women without (P < 0.001). The
      mean ovarian volume/ovary and the mean follicle number/ovary were not different.
      Use of OCP influences phenotype expression (the observable trait) of individual
      women known to suffer from PCOS by reducing hyperandrogenism. Despite taking OCP,
      women still fulfilled the revised 2003 criteria for the syndrome, as PCO
      morphology was still present. Hence, OCP use does not appreciably affect the PCOS
      phenotype.

PMID- 16417734
TI  - Comparison of effects of zona drilling by non-contact infrared laser or acid
      Tyrode's on the development of human biopsied embryos as revealed by blastomere
      viability, cytoskeletal analysis and molecular cytogenetics.
AB  - Use of a non-contact infrared laser (IRL) or acid Tyrode's for zona drilling
      before embryo biopsy was compared by assessing blastomere viability using various
      fluorescent markers or culture of the single biopsied blastomere, and, by
      cytoskeletal and molecular cytogenetic analysis of the biopsied embryos following
      culture to the blastocyst stage. There was no significant difference in the
      proportion of biopsied embryos that showed no damage in both the biopsied
      blastomere and in the remaining embryo (acid Tyrode's: 75% versus IRL: 68%), or
      in the proportion of single biopsied blastomeres that divided in culture (P >
      0.05). However, single biopsied blastomeres from laser drilled embryos showed a
      greater tendency to form miniblastocysts. The proportion of laser or acid
      Tyrode's biopsied embryos that reached the blastocyst stage by day 6 was similar,
      although evident earlier (day 5) in the laser biopsied embryos. Spindle
      abnormalities at the blastocyst stage included tripolar and tetrapolar spindles,
      but their incidence was not significantly different from controls. In addition,
      no significant difference was observed in the incidence of chromosomal
      abnormalities and mosaicism between the two groups. It is concluded that using an
      IRL at a safe working distance does not cause adverse immediate or longer term
      effects on the development of human biopsied embryos, although damage can occur
      if drilling within this distance is unavoidable. Acid Tyrode's drilling can also
      cause damage, and tended to retard blastocyst development.

PMID- 16417735
TI  - Cryopreservation of biopsied cleavage stage human embryos.
AB  - The aim was to develop a method to optimize cryopreservation of biopsied multi
      celled human embryos. Human day 3 embryos that were donated to research, along
      with those found to be chromosomally abnormal after blastomere biopsy and
      fluorescence in-situ hyridization (FISH), were cryopreserved using a slow
      freezing protocol in either standard embryo cryopreservation solution [embryo
      transfer freezing medium (ETFM), a conventional sodium-based medium] or CJ3 (a
      choline-based, sodium-free medium). After thawing, the number of intact cells was
      recorded and the previously biopsied embryos were re-analysed using FISH.
      Biopsied embryos had a lower proportion of intact blastomeres after
      cryopreservation as compared with intact embryos. However, a significantly (P <
      0.05) higher proportion of blastomeres from intact and biopsied embryos
      cryopreserved in CJ3 (84.1 and 80.1% respectively) survived after thaw than those
      in ETFM (73.6 and 50.5% respectively). The proportion of aneuploid and mosaic
      embryos was not statistically different between the two groups. In addition, the
      frequency of lost cells by aneuploid and mosaic embryos was similar. This study
      describes a new method that improves the survival of cryopreserved biopsied
      embryos, and shows that it may also be beneficial for the storage of intact human
      multi-celled embryos.

PMID- 16417736
TI  - Efficient blastomere biopsy for mouse embryo splitting for future applications in
      human assisted reproduction.
AB  - The objective of the current study was to establish a safe, efficient biopsy
      procedure for embryo splitting using the mouse model for future applications in
      human assisted reproduction. From mouse embryos at the 2-, 4-, 6- and 8-cell
      stage, half the number of blastomeres were microsurgically biopsied and
      transferred into empty mouse zonae pellucidae. Twin embryonic development was
      monitored during in-vitro culture. Blastocyst developmental rate using 2-, 4-, 6
      , and 8-cell splitting was 74.4, 75.0, 66.7 and 38.4 respectively, with
      corresponding hatching rates of 94.9, 97.5, 92.7 and 83.8%. Blastocysts from 2-,
      4-, and 6-cell splitting resulted in elevated hatching rates compared with non
      operated blastocysts (87.5%), due to the Tyrode-assisted hatching effect.
      Blastocyst morphology was superior from 2- and 4-cell splitting when compared
      with 6- and 8-cell splitting. Furthermore, outgrowth of twin blastocysts from 2-
      and 4-cell splitting showed well-developed colonies with trophoblast cells and
      clusters of ICM cells, whereas those obtained from 6- and 8-cell splitting
      frequently formed small-sized colonies. Due to the high twinning success rate
      obtained under the experimental conditions employed in this study, it appears
      that with further modifications and proper safeguards, such embryo splitting
      efforts could have potential applications in humans.

PMID- 16417737
TI  - Polymorphic variants on chromosomes probably play a significant role in
      infertility.
AB  - Polymorphic variants on chromosomes are considered 'normal', as heterochromatin
      has no coding potential and nucleolar organizing regions (NOR) contain genes
      coding for rRNA. Variants have been reported in infertility and recurrent
      abortions. With refined molecular techniques, genes for fertility and viability
      are now thought to reside in heterochromatin. DNA sequence analysis of human
      chromosome 9 has shown that it is highly structurally polymorphic, with many
      intrachromosomal and interchromosomal duplications, and contains the largest
      autosomal block of heterochromatin. Transcriptional activation of constitutive
      heterochromatic domains of the human genome in response to environmental stress
      was reported recently. Heat shock triggers the assembly of nuclear stress bodies
      on the pericentromeric heterochromatin of human chromosomes including chromosome
      9. These are characterized by an epigenetic status typical of euchromatic
      regions. On acrocentric chromosomes, NOR-associated protein count and morphology
      was reported to separate benign and malignant melanocytic lesions. Hence all
      variants may not be 'normal'. The present study of karyotyping 842 individuals
      attending an IVF clinic with primary infertility or repeated miscarriages, showed
      polymorphic variants in 28.82% of males and 17.19% of females, which was quite
      high. It is suggested that variants should not be ignored by cytogeneticists.
      Screening prospective gamete donors for chromosome variants may help enhance the
      success of IVF.

PMID- 16417738
TI  - Improved cryopreservation of human embryonic stem cells with trehalose.
AB  - Human embryonic stem (ES) cells have been established either from fresh or frozen
      embryos. The recovery rates of undifferentiated human ES cells after
      cryopreservation with conventional slow-rate freezing and rapid-thawing methods
      are relatively low. The purpose of this study was to improve cryopreservation
      efficiency by modifying conventional methods with addition of trehalose. Immature
      oocytes donated from patients undergoing IVF treatment were utilized to generate
      blastocysts. One human ES cell line (named hES1) was established and
      characterized in detail. The hES1 cells expressed regular human ES cell markers,
      including stage-specific embryonic antigens SSEA-3, SSEA-4, tumour rejection
      antigens TRA-1-60, TRA-1-81 and octamer-binding transcription factor Oct-4 with
      high levels of alkaline phosphatase and telomerase activities. Cells could be
      differentiated to form teratomas in vivo. With slow-rate freezing and rapid
      thawing methods modified by adding trehalose, the recovery rate of
      undifferentiated hES1 cells has been greatly improved from 15 to 48%. Cells
      retained pluripotency with normal karyotype after thawing. The results indicated
      that the use of trehalose is efficient and convenient for cryopreservation of
      human ES cells.

PMID- 16417739
TI  - Poor development of human nuclear transfer embryos using failed fertilized
      oocytes.
AB  - Failed fertilized human oocytes from IVF were enucleated and used as recipients
      for somatic cell nuclear transfer. The reconstructed embryos frequently formed an
      expanded nucleus from the injected genome after activation. However, subsequent
      development beyond the 1-cell stage was poor, and the resulting embryos showed
      chromosomal abnormalities. Poor development of oocytes after nuclear transfer
      contrasted with that of control, sperm-injected oocytes, which often progressed
      to cleavage stages. These results suggest that failed fertilized oocytes are not
      effective recipients for somatic cell nuclear transfer.

PMID- 16417740
TI  - Treatment of recurrent IVF failure and human leukocyte antigen similarity by
      intravenous immunoglobulin.
AB  - This study sought to assess the efficacy of intravenous immunoglobulin (IVIg) in
      improving pregnancy rates and outcome, in a select group of patients with
      repeated IVF failure and human leukocyte antigen (HLA) similarity. Couples
      suffering from recurrent IVF failure, defined as at least seven attempts at
      embryo transfer with no successful implantations, who were found to share at
      least three HLA loci, and a negative cross-match test, were included in the
      study. The treatment consisted of two 30 g IVIg doses: one before oocyte
      retrieval, and a second as soon as a fetal pulse was identified on ultrasound.
      Ten couples comprised the study group. In total, these couples had undergone 98
      IVF cycles with no successful pregnancies prior to initiation of the study.
      Following a total of 18 IVIg courses, seven women conceived, two women twice. Up
      to date, five women have delivered at least one live fetus, at 27 weeks or later.
      One woman is currently in the early third trimester of a twin pregnancy, and one
      woman had a late abortion at 19 weeks. The results suggest that couples with
      recurrent IVF failure and HLA similarity, may benefit from IVIg treatment.

PMID- 16417742
TI  - Changing genetic world of IVF, stem cells and PGD. A. Early methods in research.
AB  - Genetics proved essential to introduce IVF, preimplantation diagnosis (PGD) and
      embryo stem cells in the 1960s. Its small input in early years was confined to
      aspects such as timing follicle growth and ovulation. Modest understanding in the
      mid- to late 1980s, mostly on studies in mice, involved the actions of single
      genes and the balance between maternal and zygotic transcripts in preimplantation
      stages. Human IVF began after human oocytes were matured in vitro, and their
      meiotic chromosomes analysed. Their fertilization in vitro led to PGD and embryo
      stem cells. Unlike mouse embryos, most human embryos failed to implant, so the
      best had to be selected to improve IVF pregnancy rates. Initially, faster-growing
      embryos proved superior. Later, patterns of polarized nucleoli in pronuclei, the
      degree of blastomere fragmentation and growth of embryos in vitro to blastocysts
      provided excellent markers. Single cells could be isolated from embryos using
      micromanipulation. Stem cells from inner cell mass, a branch of IVF,
      differentiated into immortal stem cell lines in vitro if disaggregated. They
      formed virtually all body tissues in blastocysts cultured intact or when injected
      singly into recipient blastocysts. Later, the genetic controls of ES cell
      differentiation were assessed, together with factors switching them along
      specific differentiation pathways. Marker genes identified ES cells
      differentiating into various tissues.

PMID- 16417744
TI  - Changing genetic world of IVF, stem cells and PGD. B. Polarities and gene
      expression in differentiating embryo cells and stem cells.
AB  - Novel genetic techniques in the later twentieth century led to new analytical
      methods for assessing the growth of embryos and stem cells and improve
      preimplantation diagnosis. Increasing attention to the nature of polarities in
      mouse and human embryos revealed the existence of an animal-vegetal axis in human
      oocytes and embryos. Combinations of meridional and transverse cleavage
      divisions, the latter due to spindle rotation, determined the unequal division of
      ooplasm to embryonic blastomeres. Blastomeres with differing functions were
      accordingly formed in 4-cell embryos, including founders of inner cell mass and
      trophectoderm. New forms of gene analysis led to the polymerase chain reaction,
      while fluorescence in-situ hybridization revealed astonishingly high degrees of
      heteroploidy in human embryos. Developmental genetics gained immense analytical
      power as cDNA libraries, microarrays, transcriptomes RNAi and other methods
      clarified the roles of hundreds of genes in pre- and early post-implantation
      embryos and stem cells.

PMID- 16417746
TI  - Changing genetic world of IVF, stem cells and PGD. C. Embryogenesis and the
      differentiation of the haemopoietic system.
AB  - In this final review, attention is focused on the formation of several
      haemopoietic systems and their genetic markers. Very early haemopoietic
      precursors have been identified in mesoderm and yolk sac, as interactions arise
      between haemopoietic stem cells (HSC) and mesenchymal stem cells (MSC). The
      foundation cell for the haemopoietic system has not been identified, although
      several candidate cells carrying specific markers have been recognized and are
      highly pluripotent. Haemangioblasts were proposed as the founder haemopoietic
      stem cell. They may be the source of pluripotent haemopoietic cells formed in
      blastocyst injection chimaeras, a characteristic typical of ES cells. Their role
      as the founder cell of haemopoietic and mesenchymal tissues is discussed.

PMID- 16417747
TI  - Economic evaluations in healthcare: comments on a recent article.

PMID- 16417748
TI  - Adolescent bariatric surgery: treatment delayed, treatment denied, a crisis
      invited.
AB  - Adolescent obesity has serious immediate and long-term health consequences. There
      are no effective behavioral or pharmacologic treatments of extreme obesity among
      adolescents. Bariatric surgery is the most effective means to achieve durable
      weight loss, with amelioration or resolution of most obesity-related co
      morbidities. Surgery should be performed when: 1) the risk of operative
      complications and of recidivism is lowest; 2) the outcomes of the operation are
      likely to be the best possible; and 3) there is little need to consider
      subsequent bariatric surgery for weight regain and reappearance of co
      morbidities. A higher BMI is an independent risk factor for operative morbidity
      and mortality, and is associated with less weight loss and greater likelihood of
      weight regain. The higher BMI criterion for adolescent bariatric surgery exposes
      the adolescent to a higher risk for operative death and complications, and
      suboptimal outcomes following bariatric surgery.

PMID- 16417749
TI  - The plastic surgeon in the treatment of obesity.
AB  - Obesity is an increasingly common disease, whose complex treatment often
      terminates with the patient's discontinuation of therapies. The authors suggest
      how to improve a multidisciplinary approach to the obese, to increase compliance
      with therapy. A characterization of obesity is a helpful initial step. It
      consists of an accurate anatomic definition of fat distribution, which can more
      accurately be performed by imaging (U/S, CT, MRI). The patient's obesity should
      also be identified based on the physical characteristics that we propose. The
      plastic surgeon's intervention is often required and beneficial in every type of
      obesity. Many body areas are appropriate for contouring. Apart from providing a
      gain in esthetic appearance, plastic surgery also results in several benefits for
      the patient's general health.

PMID- 16417751
TI  - Outcome and complications of gastric bypass in super-super obesity versus morbid
      obesity.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) reduces the co-morbidities of
      obesity. Patients with super-super obesity (BMI>or=60) present additional
      technical and medical challenges. This study compares the results in super-super
      obese patients with patients with a BMI of <60 over a 5.5-year period. METHODS:
      Retrospective analysis was performed of the 504 patients who underwent open RYGBP
      from January 1999 through June 2004. Patients were divided into 2 groups: Group A
      (444 patients) had a BMI <60, and Group B (60 patients) had a BMI>or=60, and also
      had a greater percentage of males. The groups were otherwise similar in
      demographics and co-morbidities. RESULTS: Concomitant ventral herniorrhaphy was
      performed in 23 patients (5%) in Group A and in 3 patients (5%) in Group B.
      Concomitant cholecystectomy was done in 11.2% in Group A and 10% in Group B.
      Group A patients had an incidence of leaks of 1.3%, and there were no leaks in
      Group B. Wound infection rate for Group A was 5% vs 1.7 % in Group B (NS).
      Mortality for both groups was similar. The stricture rate for Group A was 0.9%
      compared with 1.7 % for Group B. After 1 year, excess weight lost was 41.7% in
      Group A and 38.3% in Group B. The development of anemia was not statistically
      different (8.3% vs 11.0 %). Incidence of postoperative gallbladder disease and
      incisional hernia was similar. CONCLUSIONS: Super-super-obese patients should not
      be excluded from RYGBP because of a perceived increased risk based upon BMI.

PMID- 16417750
TI  - Jejunojejunal anastomotic obstruction following laparoscopic Roux-en-Y gastric
      bypass due to non-absorbable suture: a report of seven cases.
AB  - INTRODUCTION: Small bowel obstruction (SBO) is a well-known complication of
      laparoscopic Roux-en-Y gastric bypass (LRYGBP). We describe 7 cases of
      jejunojejunal anastomotic obstruction related to adhesion formation after closure
      of the mesenteric "leaves" defect with non-absorbable suture. METHODS: All
      patients undergoing LRYGBP from October 2002 until February 2005 were entered
      into a prospective, longitudinal database. All patients who subsequently
      presented with SBO were analyzed. RESULTS: Jejunojejunal anastomotic obstruction
      occurred in 7 out of 152 patients (4.6%) in whom LRYGBP was performed from
      October 2002 to February 2004. Since February 2004, the suture used to close the
      jejunojejunal mesenteric leaves defect was changed from non-absorbable Dacron
      (Surgidac) to absorbable suture material. The mean interval between initial
      LRYGBP and subsequent SBO was 153 days. Operative findings common to all 7 cases
      were dilated loops of proximal small bowel, and a single adhesion just distal to
      the Roux-Y anastomosis. Following adhesiolysis, each patient had prompt return of
      bowel function without recurrence of obstruction. Of the 156 patients who have
      since undergone LRYGBP, none have presented with SBO, and this difference is
      statistically significant (P=0.008). CONCLUSIONS: The overall rate of SBO (2.3%)
      is consistent with the previous literature, although the incidence of adhesions
      specifically at the jejunojejunal anastomosis is higher than that previously
      encountered. It appears that the incidence of postoperative SBO at the
      jejunojejunal anastomosis is directly linked to the choice of suture material
      intraoperatively. As such, absorbable suture should be used to close the
      jejunojejunal mesenteric leaves defect.

PMID- 16417752
TI  - Gastrointestinal quality of life after laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is a commonly
      performed bariatric surgical procedure for the treatment of morbid obesity (MO).
      Obesity-related co-morbidities reduce the quality and expectancy of life. We
      assessed gastrointestinal quality of life in patients following LRYGBP. METHODS:
      The Gastrointestinal Quality of Life Index (GIQLI test) was used in this study. A
      higher score correlates with better quality of life. The GIQLI test was
      administered to 3 non-selected groups: 100 morbidly obese patients (MO group),
      100 patients who had undergone LRYGBP (LRYGBP group); and a control group of 100
      individuals (CO group). The CO group was composed of healthy individuals with a
      BMI<30 kg/m2, consecutively recruited among the companions of patients who came
      for a surgery consultation for obesity or other pathologies. Overall test and
      specific dimensions scores were evaluated for each group. RESULTS: Overall test
      and specific dimensions scores were significantly lower in patients with MO when
      compared to the CO and LRYGBP groups. There were no differences between the CO
      and LRYGBP groups in the overall score with regard to disease-specific digestive
      symptoms and the psychological and social dimensions. CONCLUSIONS: The quality of
      life of morbidly obese patients is worsened not only because of the presence of
      digestive symptoms but also because of their emotional, physical and social
      impact. Patients operated on by LRYGBP experience an improvement in their quality
      of life, with good tolerance of the anatomical changes.

PMID- 16417753
TI  - Impact of varying levels of protein intake on protein status indicators after
      gastric bypass in patients with multiple complications requiring nutritional
      support.
AB  - BACKGROUND: <6% of patients who undergo Roux-en-Y gastric bypass (RYGBP) for
      morbid obesity require nutritional support after surgery. Protein and caloric
      needs have been estimated as 14-21 kcal, 1.2 g protein/kg/current body weight/day
      in uncomplicated morbidly obese patients. This study assesses the effect of
      varying protein-calorie intake in complicated patients after RYGBP on two markers
      of protein status: thyroxine-binding prealbumin (TBPA) and serum albumin.
      METHODS: This 25-month retrospective study consisted of 22 patients with
      postoperative complications. Serum albumin, TBPA, medical nutrition care-plans,
      laboratory data and history were reviewed. These post-RYGBP patients who had
      BMI>35 and no multi-system organ failure or fistulas, had complications after
      surgery requiring nutrition support services (NSS). Serum albumin and TBPA were
      matched to fed levels of protein using random coefficient regression analysis.
      RESULTS: Mean incremental increases of 2.34 mg/dl (TBPA, P=0.0113) and 0.11 g/dl
      (serum albumin, P=0.0272) were found with each 0.5 g protein intake increase/kg
      ideal body weight/day (kg/IBW/day). Patients required NSS for 23+/-21 (mean+/-SD)
      days, with 15+/-19 days fed at goal rate. Initial serum albumin was 2.3+/-0.5,
      with a final measure of 2.7+/-0.5 g/dl. Goal protein and calorie intake were 2.1
      g and 17 kcal/kg IBW/day versus actual intake of 1.6 g and 13 kcal/kg IBW/day.
      CONCLUSION: Morbidly obese patients requiring NSS following RYGBP risk iatrogenic
      protein malnutrition. There was a positive linear relationship between protein
      status and protein intake that warrants further study of higher protein feeding
      in complicated post-RYGBP patients.

PMID- 16417754
TI  - Past use of amphetamines in candidates for gastric bypass surgery in a university
      hospital.
AB  - BACKGROUND: The authors evaluated the history of treatment in a population of
      patients awaiting gastric bypass surgery. METHODS: A standard questionnaire was
      used to evaluate the history of different therapeutic methods for weight loss in
      312 patients between 13 and 70 years of age: 247 (79.2%) women and 66 (20.8%)
      men. RESULTS: BMI varied between 33.0 to 100.0 kg/m2. The most common therapeutic
      method for losing weight was the use of formulae containing amphetamines, n=270
      (86.5%). Only a tendency could be found towards a difference between women and
      men regarding amphetamine utilization respectively: 218 (88.3%) vs 52 (80.0%);
      P=0.066. Patients used formulae for the first time at an average age of 22.5+/
      8.0 years old (from 8 to 57 years old). 43.7% (n=118) of the patients who used
      amphetamines have never received any information about the drug, and 80.6%
      (n=216) regret using this option. Dry mouth was the most common side-effect
      reported, n=205 (81%). Women had more frequent reports of depression and tremors
      than men, 58.6% vs 40.0% (P=0.017) and 44% vs 25% (P=0.011) respectively.
      CONCLUSIONS: Amphetamines were used on a large scale in this population and a
      high level of side-effects were observed. Women used them more frequently than
      men, and noted a higher level of side-effects.

PMID- 16417755
TI  - Long-term outcome of total knee replacement: does obesity matter?
AB  - BACKGROUND: Although arthritic complications are common in the obese, many
      surgeons are reluctant to perform joint replacements in this population. We
      compared outcomes of total knee arthroplasties (TKAs) in normal weight and obese
      patients. METHODS: 30 TKAs in 21 obese patients with BMI 30-49 (Group A--mainly
      mildly and moderately obese) were compared to a matched group of 53 TKAs in 41
      non-obese patients with BMI 16-29.9 (Group B). Outcome measures included the Knee
      Society Score (a composite of clinical and functional parameters), radiographic
      results, and the need for revision or reoperation. RESULTS: Median follow-up was
      11.3 years; no patients were lost to follow-up during this time. The Knee Society
      Score rose 92 points in Group A to a final score of 184, and 95 points in Group B
      to a score of 193. There was no statistical difference in Groups A and B between
      the improvement in scores or the final score achieved. Osteolysis rates were not
      significantly different between the 2 groups (5% vs 13%), nor were radiolucency
      rates (0% vs 9.7%). Median alignment was also similar in both groups (8.1 degrees
      vs 8.0 degrees valgus). 13.3% of Group A required reoperation while none required
      revision, and 13.2% of Group B required reoperation with 3.8% requiring revision.
      Survival rates were similar in both groups (71.4% vs 61.5%). CONCLUSIONS:
      Moderate obesity does not affect the clinical and radiologic outcome of TKA.
      However, TKA results in improved mobility, enhancing the success of subsequent
      weight loss therapy.

PMID- 16417756
TI  - Is collagen a good banding material for outlet control of vertical gastroplasty?
      Preliminary study in pigs.
AB  - BACKGROUND: To maintain the long-term effects of a gastric bariatric operation,
      bands are often placed to control the restriction. Erosion into the gastric wall
      by these devices remains a problem. A soft resiliant prosthesis of animal origin,
      constituted by a network of non-absorbable collagen fibres, may be a solution to
      this problem. This study assessed, in a porcine model, the histological reaction
      of the gastric wall following apposition of a band of porcine collagen (Pelvicol,
      Bard). METHODS: 15 female pigs weighing on average 21 kg underwent vertical
      banded gastroplasty (VBG). Stoma control was achieved with a band of porcine
      collagen (2 cm wide, 7 cm long and 2 mm thick). The pigs were sacrificed 1 month
      after VBG, and histological analysis was performed at a macroscopic and
      microscopic level. RESULTS: There was no peri-operative death, although 2 pigs
      died in the postoperative period (the first case developed a bowel fistula and
      sepsis, and the second pig died of unrelated causes). There were 2 additional
      morbidities (gastric fistula on the linear staple-line away from the Pelvicol
      band) that led to an early euthanasia of 2 pigs. Post-mortem macroscopic analyses
      in the remaining 11 pigs did not reveal migration of the device, and there was no
      tissue reaction on postoperative microscopic analyses. 10 of the pigs had lost
      weight at 1 month, averaging 3.42 kg. CONCLUSION: Porcine collagen appears to be
      an effective and safe alternative to the current methods of control of pouch
      outlet. The flexibility and homogeneity of this prosthesis may be useful to limit
      the risk of erosion of the gastric wall. Although these properties have been
      assessed in pelvic operations in humans, this work needs to be studied in a
      prospective long-term study in humans.

PMID- 16417757
TI  - Is routine preoperative upper endoscopy in gastric banding patients really
      necessary?
AB  - BACKGROUND: Preoperative evaluation for bariatric surgery is complex. Our
      investigation focused on the necessity for upper gastrointestinal (GI) endoscopy
      as a routine procedure before performing gastric banding. METHODS: A consecutive
      series of 145 patients underwent laparoscopic adjustable gastric banding (LAGB).
      Gastroscopy was performed routinely before LAGB. All patients were interviewed
      before gastroscopy regarding gastroesophageal symptoms. Gastroscopic findings and
      the results of the interview were blinded and set in comparison. Furthermore, we
      analyzed whether upper GI symptoms, BMI, age or gender were predictive parameters
      for pathological findings on gastroscopy. Small hiatal hernia was not considered
      a clinically relevant finding. RESULTS: Gastroscopy yielded abnormal findings in
      only 15 patients (10%). There were 8 patients with hiatal hernia, 4 patients with
      esophagitis, 1 gastric ulcer, 1 erosive gastritis, and 1 gastric polyp. Abnormal
      findings on gastroscopy did not correlate with age, BMI, or gender. The 18
      patients who reported gastroesophageal symptoms were more likely to have abnormal
      gastroscopic findings (P<0.001). Gastroesophageal symptoms had a sensitivity of
      80% and a specificity of 98% in the prediction of a GI abnormality. CONCLUSIONS:
      The data suggest that it may not be necessary to continue performing gastroscopy
      in all patients preparing for gastric banding. The data collected support the
      policy of a selective use of gastroscopy, only focusing on patients suffering
      from gastroesophageal symptoms. By following this strategy, the rate of
      preoperative gastroscopies can be reduced safely by 80%.

PMID- 16417758
TI  - A rat model of restrictive bariatric surgery with gastric banding.
AB  - BACKGROUND: Gastric banding is a well established weight reduction operation that
      is effective in the treatment of severe obesity. Its metabolic and endocrine
      mechanisms of action, however, remain unclear. The aim of this study was to
      establish a rat model of gastric banding that would replicate the procedure
      performed in human obese patients. METHODS: Male Wistar rats were submitted
      either to gastric banding (n=5) or sham gastric banding (n=4), and were followed
      for 21 days. Detailed description on how to perform gastric banding in rats are
      herein described. RESULTS: The Wistar rats submitted to gastric banding showed a
      decrease in weight gain and food intake when compared to sham-operated rats. The
      cumulative weight gain during the 21 days after the surgical procedure was 143+/
      2.58 g for the gastric banded rats and 162+/-2.48 g for the sham-operated animals
      (P=0.001). The cumulative food intake was 329+/-0.53 g for the gastric banded
      rats and 380+/-15.22 g for the sham-operated animals, also statistically
      significant (P=0.025). CONCLUSION: A rat model to study gastric banding is
      described. This model can now be used for experimental investigation of
      biochemical and molecular mechanisms of weight loss resulting from this type of
      surgery.

PMID- 16417759
TI  - Effect of laparoscopic gastric banding on esophageal motility.
AB  - BACKGROUND: Alterations in esophageal motility may occur after placement of an
      adjustable gastric band as treatment for morbid obesity, near the gastro
      esophageal junction. It causes an outlet obstruction, especially during follow-up
      after the band is filled. METHODS: 29 morbidly obese patients underwent
      conventional manometry preoperatively, 6 weeks postoperatively before and after
      filling the band and at 6 months postoperatively. A questionnaire was used to
      assess upper gastrointestinal symptoms during follow-up. RESULTS: After band
      placement, there was a significant increase in lower esophageal sphincter (LES)
      end-expiratory pressure at 6 weeks with an empty band: 1.3 (0.9-1.9) kPa (median
      (interquartile range) (P=0.003), 6 weeks with a filled band: 2.1 (1.5-2.8) kPa
      (P=0.0001), and at 6 months: 1.5 (1.3-1.9) kPa (P=0.001), compared to the
      preoperative pressure: 0.8 (0.6-1.3) kPa. Also after band placement, the high
      pressure zone length increased (preop 5.0 (4.3-6.0) cm vs 6 weeks 6.0 (5.0-6.5)
      cm (P=0.003). The propagation of peristaltic contractions was not significantly
      altered after band placement. Heartburn decreased 6 weeks postoperatively
      (P=0.04) but increased at 6 months. Heartburn at 6 months was correlated with
      pouch formation (0.667; P<0.01). CONCLUSION: Adjustable gastric band placement
      causes an increase in LES pressure and length of the high pressure zone. It
      decreases reflux symptoms in the short-term, but this effect appears not to be
      related to an effect on LES pressure or length. Pouch formation increases reflux
      symptoms without having any relationship to LES pressure and length. Band
      placement in the short-term does not disturb propagation of esophageal
      contractions.

PMID- 16417760
TI  - The use of multidisciplinary teams to evaluate bariatric surgery patients:
      results from a national survey in the U.S.A.
AB  - BACKGROUND: The degree to which U.S. bariatric surgeons use multidisciplinary
      methods to evaluate patients is unknown. METHODS: We conducted a national survey
      of practising bariatric surgeons, mailed in 3 waves from September-December 2004,
      to describe and determine predictors of surgeons' approach to the
      multidisciplinary evaluation of prospective bariatric surgery patients.
      Multivariate analyses were performed to determine patterns and predictors of
      multidisciplinary methods. RESULTS: The response rate was 62% (813/1,312).
      Although 95% of respondents reported using a multidisciplinary team, only 53% had
      a general physician, nutritionist, and mental health specialist (NIH-recommended
      team). Just 47% mandated primary care, nutrition, and mental health evaluations
      (NIH-recommended evaluations). Practice type, size, and location as well as
      membership in the American Society for Bariatric Surgery did not influence these
      outcomes. General surgery board certification reduced the odds of having an NIH
      recommended team (OR=0.56, 95%CI 0.35-0.92). Practicing bariatric surgery for >8
      years decreased the odds of reported multidisciplinary team use (OR=0.29, 95%CI
      0.10-0.82) and requiring NIH-recommended evaluations (OR=0.36, 95%CI 0.24-0.53).
      Medium volume surgeons had increased odds of reporting use of a team (OR=2.96,
      95%CI 1.22-7.18) and decreased odds of requiring NIH-recommended evaluations
      (OR=0.65, 95%CI 0.44-0.92). CONCLUSION: Inconsistent and unpredictable patterns
      of multidisciplinary methods were found. Further research should explore the
      impact of different methods on outcomes. New policies should detail a minimum
      standard for the multidisciplinary evaluation of bariatric surgery patients.
      Health professionals across disciplines are needed to assist surgeons in
      evaluating prospective bariatric surgery patients.

PMID- 16417761
TI  - Psychological profile of candidates for vertical banded gastroplasty.
AB  - BACKGROUND: Because bariatric surgery is a forced behavior modification and the
      operation represents only one element in it, behavioral and psychological factors
      play an important role in its results. Consequently, better understanding of
      candidates for bariatric surgery may improve selection for and success with this
      intervention. METHODS: In this study, the psychological profile of candidates for
      vertical banded gastroplasty (VBG) was investigated. In the context of
      preoperative psychological evaluation, 153 patients were interviewed by a
      psychologist and completed a battery of psychological tests. RESULTS: Compared to
      varying samples of the general population, candidates for VBG, especially
      females, experienced more psychological difficulties, more disturbed eating
      patterns, poor body attitude, and poor quality of life (QoL). In addition, 3
      subgroups could be identified, ranging from relatively good to relatively poor
      psychological functioning. CONCLUSION: Preoperatively, candidates for VBG
      struggle with a diversity of problems; however, some patients are less negatively
      affected by their obesity than others.

PMID- 16417762
TI  - One-year cost-effectiveness of surgical treatment of morbid obesity: vertical
      banded gastroplasty versus Lap-Band.
AB  - BACKGROUND: This study was designed as an economic evaluation alongside a
      randomized clinical trial. The object of this study was to evaluate the 1-year
      cost-effectiveness of surgical treatment of morbid obesity comparing two
      operations. METHODS: 100 patients were assigned randomly to vertical banded
      gastroplasty (VBG) or Lap-Band surgery. Both medical and non-medical costs were
      identified and measured. Costs data were combined with percentage Excess Weight
      Loss (%EWL) and with Quality Adjusted Life Years (QALYs) to obtain cost per %EWL
      and cost per QALY ratios. RESULTS: At 1 year, the total costs were not
      significantly different between both groups (95% confidence interval E5,999
      E1,765). Also, the QALY gain after surgery was not significantly different
      between the two groups. However, %EWL was significantly higher in the VBG group
      compared to the Lap-Band group, P-value .0001. The estimated incremental cost per
      %EWL was E105.83 (E1,885.91/-17.82). For the costs per QALY, the estimated ratio
      was dominant. The overall mortality in this study was 2%. 2 patients in the VBG
      group died within 30 days after surgery; 1 of these deaths was possibly related
      to the VBG procedure. CONCLUSION: At 1 year after surgery, the costs and QoL of
      the two treatment modalities were found to be equal. Therefore, the selection of
      the procedure can be based on the clinical aspects, effectivity and safety at 1
      year. In addition, the results of a long-term cost-effectiveness analysis (e.g.
      with a follow-up of 36 months) planned in the future can also be helpful in the
      selection of the preferred treatment.

PMID- 16417763
TI  - Incidental splenic artery aneurysm during laparoscopic gastric banding.
AB  - Splenic artery aneurysm occurs in approximately 1% of the population, and is four
      times more common in females. Women with a history of multiple pregnancies carry
      the highest risk. These aneurysms are usually incidental findings. Rupture
      carries a substantial mortality. Management choices include open, laparoscopic,
      and endovascular procedures. We report a 44-year-old female with a BMI of 56 who
      underwent laparoscopic gastric banding. Upon exploring the abdomen, a 4-cm
      splenic artery aneurysm was discovered. The aneurysm was excluded by proximal and
      distal surgical clips. The patient's postoperative course was unremarkable. This
      surgical technique is simple, safe, minimally invasive, and provides adequate
      therapy without incurring the morbidity associated with aneurysmectomy and
      splenectomy. It is likely that this problem will be encountered again by
      bariatric surgeons, because this area is commonly exposed. Therefore, this is
      something that bariatric surgeons should be aware of, be able to recognize, and
      understand the various therapeutic options.

PMID- 16417764
TI  - Pseudosarcoma: massive localized lymphedema of the morbidly obese.
AB  - Massive localized lymphedema is a term used to describe a benign overgrowth of
      lymphoproliferative tissue in morbidly obese patients, which is characterized by
      fibrotic and edematous fibroadipose tissue. Because of its large size and similar
      appearance to sarcomas, it has often been termed a pseudosarcoma. Patients tend
      to seek treatment only when the masses reach a sufficient size to alter their
      activities of daily living or have problems with excoriation or wound breakdown.
      Resection is indicated in these cases or if there is any question as to
      underlying malignancy of the lesion. Although recurrence is common, overall
      prognosis is good, with only anecdotal reports of transformation to angiosarcoma
      in the literature. We report a patient afflicted with this unique disorder.

PMID- 16417765
TI  - Remission of psoriasis after open gastric bypass.
AB  - Psoriasis is a frequent skin disease, affecting 2% of the world's population.
      Stress, alcohol, smoking and obesity may be associated with psoriasis. A 56-year
      old man with BMI 46.9 kg/m(2), hypertension and gastroesophageal reflux, had
      severe psoriasis for the last 39 years, without any remission on multiple
      treatments. Psoriatic papules and plaques were noted on his face, dorsum of
      hands, buttocks, knees, and elbows. He underwent open Roux-en-Y gastric bypass.
      At 4-month follow-up, the patient had lost 23 kg or 34.8% of excess weight, and
      presented complete remission of the psoriasis without medications. Bariatric
      surgery for positive metabolic, psychological and lifestyle consequences should
      be considered a treatment of psoriasis. Long-term observation is necessary.

PMID- 16417766
TI  - Laparoscopic adjustable gastric banding in a patient with an incidental para
      hiatal hernia.
AB  - Laparoscopic adjustable gastric banding (LAGB) in patients with a sliding hiatus
      hernia has become an accepted procedure. However, LAGB in patients with less
      common types of diaphragmatic hernia is rarely described. We report a super-super
      obese woman with a para-hiatal hernia (non-hiatal, diaphragmatic hernia) where
      LAGB was performed. The para-hiatal hernia was successfully repaired
      laparoscopically at the same time that the LAGB was performed. A para-hiatal
      hernia is not a contraindication to LAGB and can be repaired at the same
      operation.

PMID- 16417767
TI  - Intra-abdominal abscess in the course of intragastric migration of an adjustable
      gastric band: a potentially life-threatening complication.
AB  - Intragastric band migration is a potential complication of adjustable gastric
      banding. A 39-year-old morbidly obese female underwent laparoscopic adjustable
      gastric banding. After uneventful postoperative follow-up of 4 years, she had
      slow, steady failure of the restrictive effect, associated with regain of weight.
      Intragastric band migration was confirmed on GI series, and the patient was
      admitted to the hospital for revision. The patient presented no symptoms of acute
      abdomen. Intraoperatively, a huge intra-abdominal abscess was discovered in the
      epigastric area. The stomach with the band and tubing were involved in the
      inflammatory process. Labtobacillus acidofilus was found to be the causative
      organism. Removal of the gastric band with simultaneous resectional gastric
      bypass was performed. The recovery proceeded with no complications. Intragastric
      band migration can cause intra-abdominal abscess; thus, we believe that every
      case of band migration should be treated without delay to avoid further
      complications.

PMID- 16417769
TI  - A plan to establish private pay bariatric surgery in the U.S.A.

PMID- 16417768
TI  - Outcome of portal injuries following bariatric operations.
AB  - BACKGROUND: Portal vein thrombosis is rare following Roux-en-Y gastric bypass
      (RYGBP). Its natural history is dependent on the etiology of the thrombosis.
      Iatrogenic injuries at bariatric operations resulting in portal vein thrombosis
      are lethal complications typically necessitating a liver transplant, whereas
      postoperative portal vein thrombosis without an injury to the portal vein has a
      benign course. There are currently no data on management or prognostic factors of
      portal vein thrombosis after bariatric operations. METHODS: 3 patients referred
      for liver transplantation secondary to portal vein injury following bariatric
      surgery between 2000 and 2003 are presented. RESULTS: 2 super-obese (BMI>or=50
      kg/m2) and 1 morbidly obese (BMI 44 kg/m2) patients sustained portal vein
      injuries during bariatric surgery (RYGBP 2, VBG 1) by experienced bariatric
      surgeons. In each case, the portal injury was identified and repaired. Thrombosis
      followed reconstruction in all 3 patients. All 3 underwent emergency liver
      transplantation, but died of sepsis and multi-organ failure following
      transplantation. Review of the literature found no cases of traumatic portal vein
      injuries following bariatric operations and 2 cases of postoperative portal vein
      thrombosis: 1 following LRYGBP (BMI 46) and one after a Lap-Band (BMI 41).
      CONCLUSION: Injury to the portal vein resulting from difficulty in discerning the
      anatomy of the intra-abdominal structures in the morbidly obese, is a lethal
      complication of bariatric surgery. Super-obese patients submitting to bariatric
      surgery should lose weight, undergo a two-stage bariatric procedure, or undergo
      laparoscopic RYGBP to minimize the risk of portal injury. Postoperative portal
      vein thrombosis has a benign course and can be managed conservatively.

PMID- 16417771
TI  - Study of traditional chinese medicine-which is after all the right way?

PMID- 16417772
TI  - Evaluation of the clinical efficacy of Qingqiao capsule in treating patients with
      secretory otitis media.
AB  - OBJECTIVE: To observe the clinical efficacy of Qingqiao Capsule (QQC) in treating
      patients with secretory otitis media (SOM). METHODS: A total of 90 patients were
      randomly assigned into the treated group (n = 45) and the control group (n = 45).
      Patients in the treated group were administrated with QQC, 5 capsules each time,
      3 times a day for totally 10-14 days, and those in the control group were given
      per os cefaclor capsules 0.5 g each time for adult, 3 times a day, or 20
      mg/(kg.d) for children, for 10-14 days. The therapeutic efficacy of treatment on
      the patients was observed and compared after treatment and followed up for 3-6
      months. RESULTS: (1) The clinical efficacy in the treated group was superior to
      that in the control group with significant statistical difference (P < 0.01); (2)
      Comparison of the efficacies in patients of three different TCM syndrome types
      (the external pathogenic wind invasion caused auditory orifice stuffiness type,
      the Gan-Dan damp-heat steaming up auditory orifice type and the Pi-deficiency
      dysfunction induced dirty dampness blocking ear type) showed no statistically
      significant difference (P > 0.05); (3) The vanishing rate and time needed of the
      main symptoms and signs in the treated group were superior to those in the
      control group on ear muffle, tinnitus, hearing impairment, hydrotypanum, pure
      tone threshold and abnormal tongue figure, and the difference was statistically
      significant (P < 0.05 or P < 0.01), only those of earache, otopiesis and abnormal
      pulse figure were insignificantly different between the two groups (P > 0.05).
      CONCLUSION: QQC is an effective Chinese composite medicine on patients with SOM,
      and shows no obvious adverse reaction.

PMID- 16417773
TI  - A clinical study on the treatment of chronic pelvic inflammation of Qi-stagnation
      with blood stasis syndrome by Penyanqing capsule.
AB  - OBJECTIVE: To observe the clinical efficacy of Penyanqing Capsule (PYQC) in
      treating pelvic inflammation of Qi-stagnation with blood stasis syndrome.
      METHODS: The randomized, single blinded, parallel positive drug controlled method
      was adopted, with 82 patients assigned into two groups by envelop method. The 42
      patients in the treated group received PYQC 3 times a day, 4 capsules each time
      taken orally; the 40 patients in the control group were given orally Fuyankang
      tablets (FYKT) 3 times a day, 6 tablets each time. The therapeutic course for
      both groups was 2 months, and 2 courses of treatment were given successively to
      observe the comprehensive effect, changes of symptoms and signs before and after
      treatment. The effects of PYQC on hemorrheological character in part of the
      patients and on the pathogenetic chlamydia and mycoplasma were also observed.
      RESULTS: The total effective rate in the treated group was 83.3%, which was
      insignificantly different from that in the control group (77.5%, P > 0.05).
      However, PYQC could significantly lower the hemorrheologic indexes in patients
      and showed definite influence on the pathogenetic chlamydia and mycoplasma.
      CONCLUSION: PYQC has good therapeutic effect in treating chronic pelvic
      inflammation of Qi-stagnation with blood stasis syndrome, and showed definite
      effect on chlamydia and mycoplasma.

PMID- 16417774
TI  - A clinical study of Suogudan granule in the treatment of rheumatoid arthritis.
AB  - OBJECTIVE: To study the clinical efficacy of Suogudan Granule (SGDG) in the
      treatment of rheumatoid arthritis (RA). METHODS: Ninety patients with RA were
      randomly divided into the treated group and the control group. The treated group
      was administered orally with SGDG 6 g each time, thrice a day, while the control
      group with the combined therapy of Fenbid Capsules 0.3 g each time, twice a day
      and Tripterygium tablet 20 mg each time, thrice a day. The treatment course for
      both groups was 6 weeks. The changes of clinical symptoms and signs, and
      laboratory indices such as erythrocyte sedimentation rate (ESR), rheumatoid
      factor (RF), antistreptolysin O (ASO), routine examination of blood and urine,
      liver and kidney function, etc. before and after treatment were observed.
      RESULTS: (1) The total effective rate in the treated group (88.0%) was obviously
      higher than that in the control group (67.5%) with significant difference (P <
      0.05). (2) The improvement in arthralgia, joint swelling, time of morning
      stiffness, 15-meter walking, analgesia initiation and persistence in the treated
      group was better than that in the control group (P < 0.05, P < 0.01), but there
      was no obvious difference in improvement of joint tenderness, range of joint
      motion, grip strength, and initiating detumescence time (P > 0.05). (3) The
      improvement in ESR and RF in the treated group was better than that in the
      control group with significant difference (P < 0.05). The negative-conversion
      rate of ASO in the treated group was also higher than that in the control group
      (P < 0.01). (4) No evident abnormality in blood, urine, liver or kidney function
      was found in either group. CONCLUSION: SGDG is effective and safe for the
      treatment of RA.

PMID- 16417775
TI  - Effects of Ginkgo leaf extract on function of dendritic cells and Th1/Th2
      cytokines in patients with unstable angina pectoris.
AB  - OBJECTIVE: To investigate the effects of Ginkgo leaf extract (GLE) on function of
      dendritic cells (DC) and Th1/Th2 cytokines in patients with unstable angina
      pectoris (UAP). METHODS: Fifty-four patients with UAP were equally assigned into
      two groups, the treated group and the control group, both treated with
      conventional Western medicine, but with GLE given additionally to the treated
      group. Blood of all patients was taken before and 4 weeks after treatment to
      prepare the peripheral mononuclear cells, then which were incubated in the
      completed medium containing granulocyte-macrophage colony stimulatory factor (GM
      CSF) and interleukin-4 (IL-4) to induce mature DC. The expression of co
      stimulating factor CD86 (B7-2) on the surface of DC was detected by flow
      cytometry, and the stimulating capacity of DC was determined by mixed lymphocyte
      reaction (MLR). The blood levels of cytokines, interferon-gamma (IFN-gamma), and
      IL-4, were analyzed by ELISA, and blood C-reactive protein (CRP) level by
      turbidimetry. Moreover, the direct effect of Ginkgolide B on CD86 expression on
      DC were also tested in vitro. RESULTS: After treatment, CD86 expression on DC,
      the stimulating capacity of DC as well as levels of IFN-gamma and CRP were
      lowered in both groups (P < 0.05 or P < 0.01), but the changes were much more
      significant in the treated group than those in the control group. Ginkgolide B
      showed a direct inhibitory effect on the CD86 expression on DC. CONCLUSION: The
      inhibition of GLE on DC and thereby the suppression on inflammatory reaction may
      be one of the mechanisms of GLE in treating patients with UAP.

PMID- 16417776
TI  - Effect of Weikangfu granule on the physiopathologic figure of precancerosis of
      gastric mucosa in patients of chronic gastritis with Pi-deficiency syndrome.
AB  - OBJECTIVE: To study the physiopathologic basis of Weikangfu Granule (WKFG) in
      treating precancerosis of gastric mucosa in patients of chronic gastritis with Pi
      deficiency syndrome (CG-PDS). METHODS: One hundred and fifteen patients of CG-PDS
      who suffered from intestinal metaplasia (IM) and atypical hyperplasia (ATHP) of
      gastric mucosa, were divided into two groups. The treated group (n = 61) was
      treated by WKFG with its ingredients modified according to the syndrome type of
      patients. The control group (n = 54) was treated with Weishu granule. The
      histopathological and subcellular ultrastructural changes were detected by
      optical microscope, screening electronic microscope, transmission electronic
      microscope and histochemical staining; the nuclear and mitochondrial
      ultrastructure of gastric mucosa were analyzed with energy dispersion X-ray
      analyser and image analysis system. And the changes of cAMP, lipid peroxide
      (LPO), superoxide dismutase (SOD) before and after treatment in the treated group
      were measured and compared with those of the health control group consisting of
      15 volunteers. RESULTS: The symptomatic and pathological therapeutic effect in
      the treated group were significantly superior to those in the control group (P <
      0.05). The contents of Zn, Cu, cAMP, SOD and (3)H-TdR LCT in gastric mucosa of
      the treated group before treatment were all lower than those of the healthy
      control group, yet all these indexes markedly increased after treatment, while
      serum LPO level, which increased before treatment was lowered after treatment.
      All the changes showed statistical significance (P < 0.05 or P < 0.01).
      CONCLUSION: WKFG can reverse IM and ATHP in patients of CG-PDS, and the effect
      may be realized by way of increasing the level of Zn, Cu, cAMP and SOD in gastric
      mucosa, promoting cell differentiation, enhancing cellular immunity and reducing
      oxygen free radicals and lipid peroxidation.

PMID- 16417777
TI  - Charge couple device-based system for 3-dimensional real time positioning on the
      assessment of segmental range of motion of lumbar spine.
AB  - OBJECTIVE: To observe the tested results of the segmental range of motion (ROM)
      of lumbar spine by charge couple device (CCD)-based system for 3-dimensional real
      time positioning (CCD system), and to analyze its clinical significance. METHODS:
      Seven patients with lumbar joint dysfunction and 8 healthy subjects were tested
      twice by the CCD-based system with an interval of 10 min. RESULTS: The ROM of the
      patients was obviously lesser than that of the healthy subjects. The measuring
      data of segmental ROM of lumbar spine by CCD system is correlated significantly
      to the same data checked later on the same subjects in every direction of the
      movements. The differences between two checks are usually less than 1 degree.
      CONCLUSION: Specially designed CCD based system for 3-dimensional real-time
      positioning could objectively reflect the segmental ROM of lumbar spine. The
      system would be of great clinical significance in the assessment of the
      biomechanical dysfunction of lumbar spine and the effect of the treatment
      applied.

PMID- 16417778
TI  - Analysis of the therapeutic effect of sodium copper chlorophyllin tablet in
      treating 60 cases of leukopenia.
AB  - OBJECTIVE: To evaluate the efficacy and safety of sodium copper chlorophyllin
      (trademarked as "Yebaike Tablet which is abbreviated as YBK in treating
      leukopenia. METHODS: One hundred and five patients with leukopenia caused by
      various factors were randomized into 3 groups. The 60 patients in the YBK group
      took orally YBK Tablets at the dose of 40 mg, three times per day, the 30
      patients in the leucogen group were treated with Leucogen Tablets at the dose of
      20 mg, three times per day, and the 15 patients in the placebo group were
      administered with vitamin C tablets 100 mg, three times per day. All the subjects
      were treated for 1 month. The change of peripheral leucocytes count after
      treatment and adverse drug reaction that occurred in patients were studied.
      RESULTS: In the 60 patients treated with YBK, the treatment proved to be markedly
      effective in 34 cases, effective in 17 and ineffective in 9, the total effective
      rate being 85%, which was significantly higher than that in the placebo group
      (26.7%, P < 0.01) and similar to that in the leucogen group (83.3%, P > 0.05). No
      adverse reaction was found in the treatment course. CONCLUSION: YBK can be used
      in the treatment of leukopenia caused by various factors, satisfactory in
      efficacy and safe in use.

PMID- 16417779
TI  - Study on the effects of Guiqi Oral Liquid in promoting recovery of hematopoiesis
      in acute irradiation injured mice.
AB  - OBJECTIVE: To explore the effects and possible mechanisms of Guiqi Oral Liquid
      (GQOL) on the recovery of hematopoiesis in acute irradiation injured mice.
      METHODS: The acute irradiation injured mice were randomly divided into 2 groups:
      the treated group and the control group, and also a normal control group was set
      up with 6 mice in it receiving no treatment. After the mice in the former two
      groups were irradiated by 6.0 Gy (60)Co gamma-ray, every one of them was given
      0.4 ml GQOL or saline in equal volume through a gastric tube twice a day for 14
      days. On the 4th, 8th and 14th day after irradiation, the bone marrow mononuclear
      cells (BMMNC) and megakaryocytes in bone marrow tissues of the mice were counted,
      the proportion of hematopoietic tissues (by area) was measured, and the
      expression of adhesion molecules, CD44 and CD54, in bone marrow were estimated by
      immunochemistry. The colony forming unit of spleen (CFU-S) in the mice were
      counted on the 8th day after irradiation. RESULTS: On the 4th, 8th, 14th day
      after irradiation, the count of BMMNC and megakaryocyte, and the proportion of
      hematopoietic tissues in the treated group were higher than those in the control
      group (P < 0.01 or P < 0.05). CD44 and CD54 expression in the treated group were
      higher than those in the control group on the 4th and 8th day (P < 0.01), but
      near normal on the 14th day (P < 0.01). On the 8th day, CFU-S count in the
      treated group was higher than that in the control group (P < 0.01). CONCLUSION:
      GQOL can regulate the expression of adhesion molecules, CD44 and CD54, in the
      bone marrow of the acute irradiation injured mice, which may be one of the
      mechanisms of GQOL in accelerating the early phase hematopoiesis recovery of
      mice.

PMID- 16417780
TI  - Effects of total flavonoids of Hippophae rhamnoides L. on intracellular free
      calcium in cultured vascular smooth muscle cells of spontaneously hypertensive
      rats and Wistar-Kyoto rats.
AB  - OBJECTIVE: To explore the effects of total flavonoids of Hippophae rhamnoides L.
      (TFH), quercetin (Que) and isorhamnetin (Isor) on the intracellular free calcium
      ([Ca(2+)](i)) in vascular smooth muscle cells (VSMC) of spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). METHODS: Fluo 3
      acetoxymethylester (Fluo-3/AM) was used to observe the effects of TFH (100 mg/L)
      and its essential monomers, namely Que (10(-4) mol/L) and Isor (10(-4) mol/L) on
      changes of [Ca(2+)](i) in cultured SHR and WKY VSMC (abbr. to Ca-SHR & Ca-WKY)
      following exposure to high K(+), norepinephrine (NE) and angiotensin II (Ang II),
      and to compare with the effects of verapamil (Ver). RESULTS: (1) TFH, Que and
      Isor had inhibitory effects on resting Ca-SHR (P < 0.05), but had no significant
      effects on Ca-WKY (P > 0.05). (2) High K(+) could increase Ca-SHR more
      significantly than Ca-WKY (P < 0.05); TFH, Que and Isor could inhibit the
      elevation of [Ca(2+)](i) induced by high K(+)-depolarization, with the effects
      similar to that of Ver, and the effect on Ca-SHR was more significant than that
      on Ca-WKY (P < 0.05). (3) NE and Ang II could increase Ca-SHR more significantly
      than Ca-WKY (P < 0.05), TFH, Que and Isor had remarkably inhibitory effect on the
      elevation of Ca-SHR and Ca-WKY induced by NE or Ang II. (4) In the absence of
      extracellular Ca(2+), TFH, Que and Isor also had certain inhibitory effect on Ca
      SHR and Ca-WKY induced by NE, and the effect on the former was more significant
      than that on the latter (P < 0.05). CONCLUSION: TFH, Que and Isor might decrease
      the levels of [Ca(2+)](i) in VSMCs by blocking both voltage-dependent calcium
      channels (VDC) and receptor-operated calcium channels (ROC) in physiological or
      pathological state, which may be one of the important mechanisms of their
      hypotensive and protective effects on target organs in patients with
      hypertension.

PMID- 16417781
TI  - Protective effect of ecdysterone on PC12 cells cytotoxicity induced by beta
      amyloid25-35.
AB  - OBJECTIVE: To examine the protective effect of ecdysterone (ECR) against beta
      amyloid peptide fragment(25-35) (Abeta(25-35))-induced PC12 cells cytotoxicity,
      and to further explore its mechanism. METHODS: Experimental PC12 cells were
      divided into the Abeta group (treated by Abeta(25-35) 100 micromol/L), the blank
      group (untreated), the positive control group (treated by Vit E 100 micromol/L
      after induction) and the ECR treated groups (treated by ECR with different
      concentrations of 1, 50 and 100 micromol/L). The damaged and survival condition
      of PC12 cells in various groups was monitored by lactate dehydrogenase (LDH)
      release and MTT assay. The content of malondialdehyde (MDA) was measured by
      fluorometric assay to indicate the lipid peroxidation. And the antioxidant
      enzymes activities in PC12 cells, including superoxide dismutases (SOD), catalase
      (CAT) and glutathione peroxidase (GSH-Px), were detected respectively. RESULTS:
      After PC12 cells were treated with Abeta(25-35) (100 micromol/L) for 24 hrs, they
      revealed a great decrease in MTT absorbance and activity of antioxidant enzymes,
      including SOD, CAT and GSH-Px as well as a significant increase of LDH activity
      and MDA content in PC12 cells (P < 0.01). When the cells was pretreated with 1
      100 micromol/L ECR for 24 hrs before Abeta(25-35) treatment, the above-mentioned
      cytotoxic effect of Abeta(25-35) could be significantly attenuated dose
      dependently, for ECR 50 micromol/L, P < 0.05 and for ECR 100 micromol/L, P <
      0.01. Moreover, ECR also showed significant inhibition on the Abeta(25-35)
      induced decrease of SOD and GSH-Px activity, but not on that of CAT. CONCLUSION:
      ECR could protect PC12 cells from cytotoxicity of Abeta(25-35), and the
      protective mechanism might be related to the increase of SOD and GSH-Px
      activities and the decrease of MDA resulting from the ECR-pretreatment.

PMID- 16417782
TI  - Clinical study on effect of Osteoking in preventing postoperational deep venous
      thrombosis in patients with intertrochanteric fracture.
AB  - OBJECTIVE: To evaluate the effect of Osteoking ( masculine(1)i) in preventing
      postoperational deep venous thrombosis (DVT) in patients with intertrochanteric
      fracture (ITF). METHODS: With prospective and randomized controlled clinical
      design adopted, 62 patients with ITF after operation were assigned into 2 groups,
      the tested group and the control group, Osteoking (25 ml every other day) and
      Sanchi-dansheng tablets (3 tablets thrice a day) were given orally to them
      respectively for 10 days. Difference of round length of thighs and shanks between
      two sides were measured on the 10th day and Doppler ultrasonic examination on the
      fractured leg was carried out. RESULTS: The occurrence rate of DVT in the tested
      group was 9.4%, which was lower than that in the control group (30.0%, P < 0.05).
      All the difference of round lengths, either that of the thigh or the shank, was
      less in the tested group than that in the control group, showing statistical
      significance (P < 0.05). CONCLUSION: Osteoking has a satisfactory effect in
      preventing postoperational DVT in patients with ITF.

PMID- 16417783
TI  - Preliminary study on treatment of partial androgen deficiency in aging males with
      Jingui Shenqi Pill.
AB  - OBJECTIVE: To observe the efficacy and safety of Jingui Shengqi Pill in treating
      partial androgen deficiency in aging males (PADAM), and to explore the new
      approach in improving the quality of life in PADAM patients. METHODS: Forty
      patients with PADAM were treated with JSP, the efficacy was evaluated with
      international index of erectile function (IIEF) scoring, PADAM questionnaire
      scoring, hormone, prostatic specific antigen (PSA), etc., and the data before
      treatment were compared with those after treatment in the same group. RESULTS:
      After 3 months of treatment, PADAM scoring and IIEF scoring were all
      significantly improved. Symptoms regarding physical ability, vasomotion, and
      psychical and mental condition all got improved more markedly than symptoms
      regarding sexual hypofunction. The serum level of testosterone was 3.85 +/- 0.36
      before treatment and 5.02 +/- 0.83 after treatment (P < 0.05); luteinizing
      hormone of 7.33 +/- 2.14 and 4.84 +/- 1.43 (P < 0.01), follicle-stimulating
      hormone of 10.22 +/- 4.48 and 6.47 +/- 3.28 (P < 0.01), respectively. The level
      of PSA failed to change significantly (1.94 +/- 0.55 and 2.06 +/- 0.47, P >
      0.05). CONCLUSION: JSP is effective and safe in treating PADAM, the mechanism of
      it is different from supplementing extrinsic androgen. It may have produced the
      effect by means of favorably regulating the condition of sex hormone to improve
      the balance of pituitary-sex gland axis, so it has more extensive clinical
      application.

PMID- 16417786
TI  - Extracts of Monascusus purpureus beyond statins--profile of efficacy and safety
      of the use of extracts of Monascus purpureus.
AB  - Extracts of Monascus purpureus have always been considered a natural source of
      lovastatin, the precursor of the world's largest selling class of drugs. In
      actual fact, the fungus contains many other substances (flavonoids,
      polyunsaturated fats, pyrrolinic compounds etc.) with a wide variety of other
      actions. The most recent studies have shown that it has an action on the glycemic
      metabolism, and on the mechanisms of adipogenesis, also an effects on the
      endothelium and on postprandial vasodilation. These effects are more extensive
      and complex than those of statins alone. And new strains of Monascus purpureus
      have recently been patented where the presence of statins is only one of the
      therapeutic components of the fungus. In particular, the increase in secondary
      components, such as flavonoids, which coincides with a more complex therapeutic
      action, probably making the new extracts of Monascus purpureus, the ideal
      candidate for the treatment of the metabolic syndrome.

PMID- 16417813
TI  - Editorial: Licensing and Use of New Therapies in MS: Where Are We Going?

PMID- 16417814
TI  - Neurodegeneration and clinical relevance for early treatment in multiple
      sclerosis.
AB  - The treatment of MS with immunomodulatory agents such as interferon beta and
      glatiramer acetate, early in the disease course, is increasingly recognized as
      benefiting patient outcome. MS is a chronic inflammatory disease of the central
      nervous system with morphological hallmarks of inflammation, demyelination,
      axonal loss and gliosis. While inflammation and demyelination induce neurological
      deficit, which is at least partly reversible, axonal loss beyond the threshold of
      compensation is always accompanied by irreversible clinical disease progression.
      These neuropathological findings suggest that, in addition to reducing the impact
      of inflammation, the ability to prevent axonal degeneration is a vital component
      of MS treatment. Approved immunomodulatory therapies shift immunological status
      from a pro-inflammatory response toward more beneficial anti-inflammatory
      conditions. Clinical studies also suggest that beta interferon helps to prevent,
      and may at least partially reverse, axonal injury. Future work in this area will
      be aided by using magnetic resonance imaging (MRI) to follow hypointense lesions
      and quantification of N-acetyl aspartate by MR spectroscopy, both of which are
      potential markers of structural damage. The urgent need to identify definitive
      markers of neuroprotection in humans remains. Such markers explain more about the
      underlying mechanisms of early MS pathophysiology.

PMID- 16417815
TI  - Cyclophosphamide therapy for MS.
AB  - Cyclophosphamide has been widely studied for the treatment of MS and the
      effective stabilization of selected patients on therapy has been suggested in
      several studies. This drug has selective effects on the immune response, such as
      suppression of helper Th1 activity and enhancement of helper Th2 responses; both
      of these processes are thought to be involved in the beneficial effect of
      cyclophosphamide in MS. Over the years, especially with the advent of magnetic
      resonance imaging (MRI), there has been an improved understanding of the profound
      anti-inflammatory effect of cyclophosphamide, evidenced by its effect on clinical
      relapses and contrast-enhancing lesions on MRI. Toxic effects on the bladder and
      the risk of malignancy prevent the widespread use of cyclophosphamide in early
      MS; however, it can be dosed safely and is usually well tolerated in actively
      progressing relapsing-remitting or early secondary progressive MS cases that are
      unresponsive to beta interferon and glatiramer acetate.

PMID- 16417816
TI  - Managing specific symptoms in people with multiple sclerosis.
AB  - Besides immunomodulation and immunosuppression, symptomatic treatment is an
      important part of MS therapy. Its goals are the elimination and reduction of
      symptoms that impair functional ability and quality of life, and also the
      avoidance of secondary complications. There are many treatment recommendations
      for MS symptoms, therefore clear and consensually developed therapeutic
      strategies are needed. This paper reviews some recommendations for the treatment
      of MS-related spasticity, fatigue, pain and neurogenic bladder dysfunction that
      have been established by the Multiple Sclerosis Treatment Consensus Group of the
      German MS Society.

PMID- 16417817
TI  - Therapeutic developments in MS: report from the 57th Annual Meeting of the
      American Academy of Neurology (AAN), 9-15 April 2004, Miami, Florida, USA.
AB  - Over 6000 neurologists and neuroscientists from around the world gathered in
      April at the 57th Annual Meeting of the American Academy of Neurology (AAN).
      There were several scientific platform sessions devoted to MS at the meeting,
      concentrating on recent clinical trials (including new natalizumab data),
      outcomes assessment, imaging, surrogate markers and mechanism of action of
      current therapeutics. During the meeting, the 2005 John Dystel Prize for MS
      Research was awarded to Jack Antel of McGill University, Montreal, Canada.
      Professor Antel was honoured for his major contributions to research into
      interactions between the immune system and the brain, and its application to MS,
      and for his role as a leading MS clinician and investigator. Additional
      activities devoted to MS were posters, educational courses and seminars covering
      a wide variety of topics. This report focuses on some of the key studies
      presented in the field of therapeutic developments in MS.

PMID- 16417818
TI  - Treatment of multiple sclerosis with human beta interferon.
AB  - The present manuscript uses an evidence-based approach to review and analyse
      evidence for the use of human beta interferon in the treatment of MS. Human beta
      interferon modulates many of the biological processes believed to be involved in
      MS development. Beta interferon is a member of a large family of secreted
      proteins that are involved in an organisms defence against viral infections, cell
      growth regulation and in modulation of immune response. The therapeutic efficacy
      of beta interferon in relapsing-remitting and secondary progressive MS has been
      established in several clinical trials, and evidence indicates that the total
      weekly dosage of beta interferon and/or the frequency of beta interferon
      administration are important factors in its clinical use. Future therapeutic
      developments in MS will be fuelled by our increasing understanding of the
      physical and biological roles of the interferons, in health and in MS
      pathogenesis.

PMID- 16417819
TI  - Motivating MS patients: the Annual Convention 2005 of the MS Forum, 22 May 2005,
      St Julians, Malta.
AB  - Motivation is a key issue for everyone caring for people with MS. One needs to
      consider how best to motivate healthcare professionals so that optimum patient
      management is maintained over the long term. In addition, there is the aspect of
      patient motivation, so that people continue the treatments available to them.
      This report focuses on three plenary presentations given when the extended MS
      Forum group discussed patient motivation, during the Annual Convention 2005.

PMID- 16417820
TI  - Treatment adherence: what is the best that can be achieved?
AB  - The modest effectiveness of disease modifying therapies (DMTs) in MS has been
      amply illustrated by a series of pivotal trials, albeit short term in the context
      of a life-long disease. Most neurologists and people with MS welcome the
      opportunity to affect the course of this disorder. However, the individual with
      MS might not be fully aware of the importance of continuing treatment with these
      drugs in the absence of feeling better (and often feeling worse) while taking
      therapy.

PMID- 16417821
TI  - Mitoxantrone in the treatment of multiple sclerosis.
AB  - Mitoxantrone is useful for the treatment of cancer and MS and, as with other
      chemotherapeutic agents, many studies have examined its tolerability. The
      suitability of mitoxantrone in MS is particularly interesting because of its role
      in treating various stages of the disease. Evidence shows that mitoxantrone could
      be a first-line treatment for malignant forms of MS, and a second-line drug in
      relapsing-remitting or secondary progressive MS that is unresponsive to
      interferon beta-1a, -1b or glatiramer acetate. Mitoxantrone should, however, be
      restricted to patients with demonstrable inflammatory disease activity, and
      should only be prescribed by neurologists with previous experience in both MS and
      mitoxantrone therapy. This review examines the properties of mitoxantrone, its
      tolerability, and discusses its suitability for treating various forms of MS,
      referring to several important studies.

PMID- 16417822
TI  - Polyunsaturated fatty acid supplementation in MS.
AB  - This article focuses on polyunsaturated fatty acid (PUFA) supplementation, which
      is a popular form of complementary and alternative therapy among people with MS.
      Owing to their popularity, clinicians should be knowledgeable about the PUFA
      supplements that are widely available, and the efficacy and safety data from
      clinical studies. Small-scale studies have demonstrated trends towards some
      beneficial effects. PUFA supplementation is generally well tolerated, although
      some specific supplements are best avoided and some clinical situations warrant
      caution. A review of the efficacy and safety data suggests that PUFA
      supplementation may be a promising approach. Large-scale trials are required to
      confirm the benefits.

PMID- 16417823
TI  - Use and abuse of lasers in periodontics.

PMID- 16417824
TI  - Noncarious cervical lesions: graft or restore?

PMID- 16417825
TI  - Chairside replacement of posterior teeth using a prefabricated fiber-reinforced
      resin composite framework technique: a case report.
AB  - The fixed replacement of a single posterior missing tooth for those patients who
      cannot have either implants or conventional laboratory-generated fixed prostheses
      has always been a challenge to clinicians. The development of fiber-reinforced
      composites (FRCs) has opened up new possibilities of chairside treatment options
      to manage these types of clinical situations. Techniques using FRCs as frameworks
      with traditional restorative resin composites as veneering materials can provide
      chairside fixed prostheses that are esthetic and potentially durable, with
      minimal abutment tooth loss. A clinical case is presented that will illustrate a
      novel concept for tooth replacement--the use of an FRC prefabricated framework-
      to allow for a single visit, chairside replacement of a missing molar. The
      assembly of the framework and the clinical steps used in the framework placement
      and pontic fabrication are shown in detail. CLINICAL SIGNIFICANCE: The
      combination of FRC technology and adhesive techniques can provide minimally
      invasive and cost-effective treatment options for the chairside replacement of
      missing posterior teeth.

PMID- 16417827
TI  - Effect on enamel microhardness of two consumer-available bleaching solutions when
      compared with a dentist-prescribed, home-applied bleaching solution and a
      control.
AB  - BACKGROUND: There exists limited data in the literature regarding the efficacy
      and safety of consumer-available, paint-on bleaching solutions. PURPOSE: The
      purpose of this in vitro study was to evaluate the effect of two consumer
      available, paint-on bleaching products on enamel microhardness against a control
      and a dentist-prescribed, home-applied (DPHA) bleaching product. MATERIALS AND
      METHODS: Eighty enamel slabs were obtained from extracted human teeth and
      randomly divided into four treatment groups: (1) control; (2) Opalescence
      (Ultradent Products, Inc., South Jordan, UT, USA); (3) Crest Night Effects
      (Procter & Gamble, Cincinnati, OH, USA); and (4) Colgate Simply White Night
      (Colgate-Palmolive Co., Piscataway, NJ, USA). Opalescence is a carbamide peroxide
      DPHA product, whereas Crest Night Effects and Colgate Simply White Night are
      consumer-available products. The specimens in groups 2 to 4 underwent 2 weeks of
      treatment for 8 h/d. Specimens were maintained in artificial saliva at 37 degrees
      C between treatments. Subsequently, one-half of the specimens in groups 2 to 4
      (n=10) underwent an additional seven treatments for 8 h/d, while the other half
      were stored in artificial saliva, receiving no further treatment. Microhardness
      was measured as Knoop hardness numbers (KHNs) at baseline and after 1, 7, 14, and
      21 treatment days. The results were analyzed for statistical significance both
      intra- and intergroups using analysis of variance (p=.05). RESULTS: A
      statistically significant reduction in mean KHN was observed compared with
      baseline at 1, 7, 14, and 21 treatment days for group 4 and at 7 treatment days
      for group 3. When compared with the control or DPHA product, group 4 was the only
      treatment that resulted in significantly lower mean KHNs at 7, 14, and 21
      treatment days. CONCLUSION: When evaluating enamel microhardness, consumer
      available, paint-on bleaching solutions may adversely affect enamel microhardness
      compared to a control and 10% carbamide peroxide DPHA bleaching solution.
      CLINICAL SIGNIFICANCE: With numerous consumer-available bleaching products on the
      market, it is crucial to be judicious in their selection and use. The results of
      this in vitro study showed that the consumer-available, paint-on bleaching
      solutions adversely affected enamel microhardness at some time during the study.
      Consumers should be made aware of this effect on enamel.

PMID- 16417829
TI  - Clinical color match of porcelain visual shade-matching systems.
AB  - BACKGROUND: Accuracy of the total color replication process has not been
      clinically evaluated for various porcelain visual shade-matching systems.
      PURPOSE: The purpose of this study was to evaluate the final color replication
      process of three porcelain visual shade-matching systems. Subjects' natural
      dentition was compared with laboratory-fabricated individualized porcelain shade
      tabs. MATERIALS AND METHODS: Shade matches of 10 subjects' incisors were obtained
      using three different porcelain visual shade-matching systems. Commercial
      laboratories fabricated one corresponding individualized porcelain shade tab for
      each incisor per visual shade-matching system selection. Color-match evaluations
      of the fabricated individualized porcelain shade tabs to the corresponding teeth
      were completed by prosthodontists' consensus and by subjects' self-evaluation
      using the US Public Health Service criteria. Statistical analysis was carried out
      on the combined evaluations with logistic regression and the Generalized
      Estimating Equation for repeated measures. RESULTS: The Vitapan 3D Master/Omega
      900 system (Vident Inc., Brea, CA, USA) was significantly more likely than the
      Vita Lumin Vacuum/VMK 68 system (Vident Inc.) to obtain a clinically acceptable
      color match (odds ratio [OR]=6.31; 95% CI=1.24-32.07). The likelihood of
      obtaining a clinically acceptable color match through subjects' self-evaluation
      was found to be significantly higher compared with prosthodontists' consensus
      (OR=2.75; 95% CI=1.27-5.94). CONCLUSIONS: Within the limits of this preliminary
      study, significant differences in clinical acceptability were seen between the
      color matches of the fabricated individualized porcelain shade tabs from
      different systems and subjects' central incisors. Subjects' range of
      acceptability was much broader compared with that of the prosthodontists in
      assessing the color match of the fabricated porcelain shade tabs. CLINICAL
      SIGNIFICANCE: The use of certain porcelain visual shade-matching systems may
      result in a clinically acceptable color match of the final restoration more
      readily than the use of other systems. Color-match evaluation of final
      restorations should be accomplished through a consensus between prosthodontists
      and patients, given the difference in thresholds of acceptability.

PMID- 16417831
TI  - Flexural strength and modulus properties of carbamide peroxide-treated bovine
      dentin.
AB  - BACKGROUND: The effects of carbamide peroxide bleach on tooth structure are
      uncertain. PURPOSE: The purpose of this study was to investigate the effects of
      direct or indirect carbamide peroxide application on dentin flexural strength and
      modulus in vitro. MATERIALS AND METHODS: Dentin bars were machined from bovine
      incisors and treated with 10% carbamide peroxide for 6 h/d for 14 days. Four
      groups were created, with eight bars in each group: group 1-direct bleach
      application only; group 2-indirect bleach application only; group 3-direct bleach
      application followed by a 2-week storage in artificial saliva; group 4-direct
      bleach application followed by a 2-week storage in artificial saliva and daily
      topical fluoride treatments. The specimens' flexural strength and modulus were
      tested after 24 hours, and the results were compared with water controls using
      independent t-tests (p < .05). RESULTS: Flexural strength results (in
      megapascals) for bleached versus control dentin (1=205+/-26 vs 215+/-14, 2=257+/
      25 vs 261+/-14, 3=180+/-22 vs 193+/-36, 4=157+/-18 vs 184+/-11) were
      significantly lower in group 4 (p=.005). Modulus results (in gigapascals) for
      bleached versus control dentin (1=10.7+/-1.4 vs 12.2+/-0.6, 2=14.2+/-1.7 vs
      14.4+/-1.6, 3=10.0+/-2.0 vs 10.9+/-1.3, 4=9.0+/-1.2 vs 11.1+/-1.0) were
      significantly lower in groups 1 and 4 (p=.013 and p=.003, respectively). There
      were no significant differences in strength and modulus results between the
      bleached and control dentin in groups 2 and 3. A direct application of carbamide
      peroxide to bovine dentin significantly decreased some dentin mechanical
      properties in vitro. An indirect application of carbamide peroxide to dentin did
      not significantly decrease dentin strength and stiffness. CLINICAL SIGNIFICANCE:
      This in vitro study suggests that a bleaching treatment, when applied to the
      enamel of intact teeth, does not significantly affect the mechanical properties
      of the underlying dentin. However, when applied directly to dentin in clinical
      situations such as root exposure or occlusal attrition, the bleaching treatment
      may result in altered mechanical properties of dentin. The clinical consequences
      of this observation are, however, unknown.

PMID- 16417835
TI  - Critical appraisal: tooth whitening in children and adolescents.

PMID- 16417833
TI  - Two-year clinical evaluation of nonvital tooth whitening and resin composite
      restorations.
AB  - BACKGROUND: Adhesive systems, resin composites, and light curing systems
      underwent continuous improvement in the past decade. The number of patients
      asking for ultraconservative treatments is increasing; clinicians are starting to
      reevaluate the dogma of traditional restorative dentistry and look for
      alternative methods to build up severely destroyed teeth. PURPOSE: The purpose of
      this study was to evaluate the efficacy of nonvital tooth whitening and the
      clinical performance of direct composite restorations used to reconstruct
      extensive restorations on endodontically bleached teeth. MATERIALS AND METHODS:
      Twenty-one patients 18 years or older were included in this clinical trial, and
      26 endodontically treated and bleached maxillary and mandibular teeth were
      restored using a microhybrid resin composite. Patients with severe internal
      (tetracycline stains) and external discoloration (fluorosis), smokers, and
      pregnant and nursing women were excluded from the study. Only patients with A3 or
      darker shades were included. Teeth having endodontic access opening only to be
      restored were excluded; conversely, teeth having a combination of endodontic
      access and Class III/IV cavities were included in the study. A Vita shade guide
      (Vita Zahnfabrik, Bad Sackingen, Germany) arranged by value order was used to
      record the shade for each patient. Temporary or existing restorations were
      removed, along with a 1 mm gutta-percha below the cementoenamel junction (CEJ),
      and a resin-modified glass ionomer barrier was placed at the CEJ. Bleaching
      treatment was performed using a combination of in-office (OpalescenceXtra,
      Ultradent Products, South Jordan, UT, USA) and at-home (Opalescence 10% PF,
      Ultradent Products) applications. Two weeks after completion of the bleaching,
      the teeth were restored using a combination of PQ1 adhesive system and Vit-l
      escence microhybrid resin composite (Ultradent Products). Wedge-shaped increments
      were placed and cured using the VIP Light (Bisco, Inc Schaumburg, IL, USA)
      through a combination of pulse and progressive curing techniques. RESULTS: All
      but one restoration were evaluated by two independent evaluators every 6 months
      during a 2-year period using modified US Public Health Service criteria. No
      restoration failed and "alpha" scores were recorded for all parameters but color
      stability, which was scored "bravo." Analysis of variance showed a significant
      shade change between baseline (mean=14.4+/-1.9) versus 2 weeks (mean=1.6+/-0.7)
      and 2 years (mean=2.8+/-1.7) (p<.0001). Although a significant shade change was
      observed between 2 weeks and the 2-year follow-up (p=.008), no significant
      difference was reported between the baseline and 2 weeks (12.9+/-2) versus
      baseline and 2 years (11.9+/-2.3). CONCLUSIONS: Significant tooth lightening was
      reported after the completion of whitening therapy on devitalized teeth; shade
      rebound was reported in less than 50% of the treated teeth and was limited to a
      maximum of four shades. A microhybrid resin composite demonstrated excellent
      clinical performance in the restoration of all endodontically treated and
      bleached teeth after a 2-year evaluation period. CLINICAL SIGNIFICANCE: Nonvital
      tooth whitening is responsible for a significant change in color of
      endodontically stained teeth. Successful nonvital tooth-whitening therapy allows
      for conservative tooth preparation, preserving and reinforcing sound tooth
      structure. The proper use of modern adhesive systems along with resin composite
      restorations precludes the use of more extensive restorative treatment, delaying
      expensive crown and bridge procedures.

PMID- 16417836
TI  - Talking with Patients. Microabrasion.

PMID- 16417839
TI  - Neuroimaging in cerebral palsy: Patterns of brain dysgenesis and injury.
AB  - Despite advances in obstetric and neonatal care, the overall prevalence of
      cerebral palsy has remained stable, supporting the belief that pathogenesis is
      primarily due to prenatal brain dysgenesis and injury. Neuroimaging studies have
      consistently shown abnormalities in 70% to 90% of affected children, facilitating
      clinical classification into groups with early brain malformations, white-matter
      injury, neonatal encephalopathies, and a heterogeneous group of postnatally
      acquired disorders. White-matter injury, well seen on conventional magnetic
      resonance imaging (MRI), is the leading cause of cerebral palsy in children born
      preterm. As many as 20% of very low birthweight infants have cystic and/or
      diffuse white-matter injury, termed periventricular leukomalacia, with evidence
      of associated pathology in other cortical and subcortical structures. In the
      group with acute, term perinatal pathology, a variety of imaging modalities, in
      addition to MRI, have diagnostic utility. In general, when added to conventional
      MRI, advanced techniques, such as diffusion tensor imaging, diffusion-weighted
      imaging, and magnetic resonance spectroscopy, provide a more complete picture of
      structural and functional brain abnormalities. The results have led to improved
      understanding of pathogenesis, especially in regard to periventricular
      leukomalacia and hypoxic-ischemic encephalopathy. This information might lead to
      interventions preventing brain injury in preterm infants and asphyxiated term
      newborns.

PMID- 16417840
TI  - Neuropathologic substrate of cerebral palsy.
AB  - Animal models have assisted in understanding the mechanisms of brain injury
      underlying cerebral palsy. Nevertheless, no such models replicate every aspect of
      the human disease. This review summarizes the classic and more recent studies of
      the neuropathology of human perinatal brain injury most commonly associated with
      cerebral palsy, for use by researchers and clinicians alike who need to analyze
      published animal models with respect to their fidelity to the human disorder. The
      neuropathology underlying cerebral palsy includes white-matter injury, known as
      periventricular leukomalacia, as well as germinal matrix hemorrhage with
      intraventricular extension, and injury to the cortex, basal ganglia, and
      thalamus. Each has distinctive features while sharing some risk factors, such as
      prematurity and/or hypoxia-ischemia in the perinatal period. Periventricular
      leukomalacia consists of diffuse injury of deep cerebral white matter, with or
      without focal necrosis. Recent work directly in human postmortem tissue has
      focused on the role of free radical injury, cytokine toxicity (especially in
      light of the epidemiologic association of periventricular leukomalacia with
      maternofetal infection), and excitotoxicity in the development of periventricular
      leukomalacia. Premyelinating oligodendrocytes, which predominate in
      periventricular regions during the window of vulnerability to periventricular
      leukomalacia (24-34 postconceptional weeks), are the targets of free radical
      injury, as determined by immunocytochemical markers of lipid peroxidation and
      protein nitration. This maturational susceptibility can be attributed in part to
      a relative deficiency of superoxide dismutases in developing white matter.
      Microglia, which respond to cytokines and to bacterial products such as
      lipopolysaccharide via Toll-like receptors, are increased in periventricular
      leukomalacia white matter and can contribute to cellular damage. Indeed, several
      cytokines, including tumor necrosis factor-a and interleukins 2 and 6, as well as
      interferon-g, have been demonstrated in periventricular leukomalacia. Preliminary
      work suggests a role for glutamate receptors and glutamate transporters in
      periventricular leukomalacia based on expression in human developing
      oligodendrocytes. Germinal matrix hemorrhage, with or without intraventricular
      hemorrhage, occurs in premature infants and can coexist with periventricular
      leukomalacia. Studies in human germinal matrix tissue have focused on maturation
      based vascular factors, such as morphometry and expression of molecules related
      to the structure of the blood-brain barrier. Gray-matter injury, seen more
      commonly in term infants, includes cortical infarcts and status marmoratus.
      Subtle cortical injury overlying periventricular leukomalacia is the subject of
      current interest as a possible substrate for the cognitive difficulties seen in
      patients with cerebral palsy. In summary, it is hoped that work in human tissue,
      in conjunction with experimental animal models, will lead to eventual therapeutic
      or preventive strategies for the perinatal brain injury underlying cerebral
      palsy.

PMID- 16417841
TI  - Role of glutamate receptors in periventricular leukomalacia.
AB  - Periventricular leukomalacia is a form of white-matter injury that occurs in the
      setting of either primary or secondary hypoxia-ischemia in the premature infant.
      Hypoxia-ischemia induces increases in cerebral extracellular glutamate levels,
      thereby activating glutamate receptors on a variety of cell types within the
      white matter. This review examines the evidence of a role for glutamate receptors
      in white-matter injury and periventricular leukomalacia. Multiple glutamate
      receptor subtypes exist, and these appear to play differential roles depending on
      cell type and time after injury. Glutamate receptors are developmentally
      regulated on neurons and glia, and certain subtypes are transiently overexpressed
      in developing rodent brain and are expressed on immature oligodendrocytes in
      human white matter in the premature period. Pharmacologic agents acting on
      glutamate receptors might represent age-specific therapeutic strategies for the
      treatment of periventricular leukomalacia.

PMID- 16417842
TI  - Maturational effects of lipopolysaccharide on white-matter injury in fetal sheep.
AB  - White-matter damage has been associated with the development of cerebral palsy in
      children born both prematurely and at term, and it has been suggested that
      intrauterine infection can contribute to the brain injury. However, the relative
      importance of age on white-matter injury following infectious exposure in utero
      remains unclear. In this study, fetal sheep were exposed to systemic endotoxemia
      by administration of Escherichia coli lipopolysaccharide (88.7 +/- 7.7 ng/kg) at
      65% or 85% of gestation. These gestational ages approximately correspond to human
      brain development in preterm and near-term infants respectively. White-matter
      injury was evaluated 3 days after lipopolysaccharide exposure with regard to
      microglia activation and loss of neurofilament and myelin basic protein. The
      expression of oligodendrocytes at different maturational stages was demonstrated
      in preterm and near-term fetuses with the oligodendroglial markers O4 and 2 ,3 
      cyclic nucleotide 3 -phospodiesterase. Forty percent of the fetuses in the
      preterm group and 22% in the near-term group died within 8 hours of the endotoxin
      exposure. Three of six preterm and two of seven near-term surviving fetuses
      demonstrated pathologic changes in the brain with regard to increased microglia
      activation and loss of neurofilament staining. The number of activated microglia
      was enhanced in the subcortical white matter in both the preterm
      lipopolysaccharide-exposed fetuses (lipopolysaccharide: 235 +/- 64 cells/mm2;
      control: 72 +/- 28 cells/mm2; P = .0374) and the near-term fetuses
      (lipopolysaccharide: 180 +/- 40 cells/mm2; control 23 +/- 16 cells/mm2; P =
      .0152). There was a loss of neurofilament staining in both preterm fetuses
      (lipopolysaccharide: 2.20 +/- 0.77 pixel units; control: 0.20 +/- 0.10 pixel
      units; P = .0306) and near-term fetuses (lipopolysaccharide: 1.15 +/- 0.48 pixel
      units; control: 0.06 +/- 0.06 pixel units; P = .0285). O4-positive cells were
      detected at both gestational ages, whereas 2,3-cyclic nucleotide 3
      phospodiesterase-positive cells and myelin basic protein staining were mainly
      detected in the near-term fetuses. In summary, we found white-matter injury in a
      proportion of both preterm and near-term fetuses after administration of
      lipopolysaccharide. These results are in agreement with clinical evidence
      suggesting that both preterm and term infants are at risk of periventricular
      leukomalacia in association with intrauterine infection.

PMID- 16417843
TI  - Patterns of cerebral injury in a primate model of preterm birth and neonatal
      intensive care.
AB  - Very preterm birth is associated with significant neurodevelopmental morbidity,
      with 10% to 15% of these infants later developing cerebral palsy and up to 50%
      experiencing learning disabilities. The nature of the cerebral lesion
      predisposing these infants to such impairments is not fully understood but is
      likely related to both cerebral injury and alterations in cerebral development
      associated with neonatal intensive care. To study the impact of both preterm
      birth and neonatal intensive care on the immature brain, we are studying a
      preterm primate model delivered at 125 days of a 184-day gestational period and
      cared for in a neonatal intensive care unit for 2 to 4 weeks in a fashion highly
      similar to that for human preterm infants. The most common neuropathology in this
      model is white-matter damage manifested by reactive astrogliosis or activated
      microglia and enlarged ventricular size. Subarachnoid, germinal matrix, and
      intraventricular hemorrhages are also common. These preliminary results support
      the similarity of this model to both the alterations in cerebral developmental
      and the pattern of cerebral injury found in human preterm infants. We are now
      investigating the impact of randomized respiratory therapies on the pattern of
      cerebral injury. The prematurely born baboon appears to be an accurate and
      relevant model for the study of preterm human birth.

PMID- 16417844
TI  - Neuronal migration disorders.
AB  - Improvement in imaging techniques has provided new classifications of neuronal
      migration disorders and their diagnosis in the developing or adult brain. Control
      of neuronal migration involves different cell populations, including Cajal
      Retzius neurons, subplate neurons, neuronal precursors, or radial glia. The
      integrity of multiple molecular mechanisms, such as cell-cycle control, cell-cell
      adhesion, interaction with extracellular matrix protein, neurotransmitter
      release, growth factor availability, platelet-activating factor degradation,
      peroxisomal metabolism, or transduction pathways, seems to be critical for normal
      neuronal migration. The present review focuses on animal models of neuronal
      migration disorders.

PMID- 16417845
TI  - Model of cerebral palsy in the perinatal rabbit.
AB  - Perinatal brain injury results in one of the highest burdens of disease in view
      of the lifelong consequences and is of enormous cost to society. This makes it
      imperative to develop better animal models that mimic the human condition. Many
      neurodevelopmental deficits, such as cerebral palsy, are believed to be a result
      of prenatal hypoxia-ischemia in humans. Fetal global hypoxia-ischemia is most
      commonly a consequence of acute placental insufficiency. Our laboratory has
      modeled in utero sustained and repetitive hypoxia-ischemia in the pregnant rabbit
      to mimic the insults of abruptio placenta and labor, respectively. Sustained
      hypoxia-ischemia at 70% (22 days' gestation) and 79% (25 days' gestation) and
      repetitive hypoxia-ischemia at 90% gestation (28 days' gestation) caused
      stillbirths and multiple deficits in the postnatal survivors. The deficits
      included impairment in multiple tests of spontaneous locomotion, reflex motor
      activity, motor responses to olfactory stimuli, and the coordination of suck and
      swallow. Hypertonia was observed in the 22 and 25 days' gestation survivors but
      not in the 28 days' gestation group. Hypertonic survivors were artificially fed
      and found to have the motor deficits persist for at least 11 postnatal days. A
      spectrum of brain abnormalities is found on magnetic resonance imaging. This is
      the first animal model to mimic cerebral palsy. The findings also suggest a
      window of vulnerability during brain development when the injury results in
      hypertonia in newborn pups.

PMID- 16417846
TI  - Immature mouse unilateral carotid ligation model of stroke.
AB  - Cerebral palsy in humans results from a diverse group of disorders that produce
      nonprogressive motor impairments in the developing brain. Stroke is an important
      cause of hemiparetic cerebral palsy in neonates and young children. We recently
      developed a new immature mouse model of stroke that demonstrates seizures, the
      severity of which correlates with brain injury. This model has strengths compared
      with other immature rodent models of ischemic injury, such as relative technical
      ease and the presence of seizures, as is seen in humans. This model also has
      relative weaknesses, such as the inability to titrate the severity of the injury
      with different periods of hypoxia. In addition, more work is needed to delineate
      the long-term consequences of the insult in this new model.

PMID- 16417847
TI  - Models of cerebral palsy: which ones are best?

PMID- 16417848
TI  - Multiple cardiac rhabdomyomas as a sole symptom of tuberous sclerosis complex:
      case report with molecular confirmation.
AB  - We report a child in whom multiple cardiac rhabdomyomas were identified on
      routine fetal ultrasonography. Molecular genetic studies identified the TSC2 gene
      missense mutation (E36; 4672 G>A, 1558 E>K TSC2). Both general and
      neurodevelopment of the patient have been normal. When last examined at age 6
      years, he had no skin manifestations of tuberous sclerosis complex. Computed
      tomography of the brain revealed two periventricular calcifications consistent
      with the molecular diagnosis. This is the first report of molecularly confirmed
      tuberous sclerosis complex in a child with multiple cardiac rhabdomyomas and no
      other clinical manifestations of the disease. We propose that all cases of
      multiple cardiac rhabdomyomas in an infant be given a tentative diagnosis of
      tuberous sclerosis complex.

PMID- 16417849
TI  - Reversible posterior leukoencephalopathy syndrome: report of three cases.
AB  - Reversible posterior leukoencephalopathy syndrome is characterized clinically by
      headache, abnormalities of mental status and visual perception, and seizures.
      Despite its diverse causes, common precipitating factors are defined as abrupt
      elevations of blood pressure, renal decompensation, fluid retention, and
      immunosuppressive therapy. We report three children with reversible posterior
      leukoencephalopathy syndrome presenting with generalized seizures and headache.
      The causes of reversible posterior leukoencephalopathy syndrome were considered
      to be acute hypertension and immunosuppressive therapy in case 1 with systemic
      lupus erythematosus, chemotherapy (vincristine and/or actinomycin-D) and
      hyponatremia in case 2, and acute hypertension in case 3, admitted with a
      familial Mediterranean fever attack. In light of these cases, we review the
      literature for the etiology, clinical and laboratory findings, and pathogenetic
      mechanisms of the disease.

PMID- 16417850
TI  - What is attention-deficit hyperactivity disorder (ADHD)?
AB  - Attention-deficit hyperactivity disorder (ADHD) is described as the most common
      neurobehavioral condition of childhood. We raise the concern that ADHD is not a
      disease per se but rather a group of symptoms representing a final common
      behavioral pathway for a gamut of emotional, psychological, and/or learning
      problems. Increasing numbers of children, especially boys, are diagnosed with
      ADHD and treated with stimulant medications according to a simplified approach.
      Methodical review of the literature, however, raised concerning issues. "Core"
      ADHD symptoms of inattentiveness, hyperactivity and impulsivity are not unique to
      ADHD. Rates of "comorbid" psychiatric and learning problems, including depression
      and anxiety, range from 12 to 60%, with significant symptom overlap with ADHD,
      difficulties in diagnosis, and evidence-based treatment methods that do not
      include stimulant medications. No neuropsychologic test result is pathognomic for
      ADHD, and structural and functional neuroimaging studies have not identified a
      unique etiology for ADHD. No genetic marker has been consistently identified, and
      heritability studies are confounded by familial environmental factors. The
      validity of the Conners' Rating Scale-Revised has been seriously questioned, and
      parent and teacher "ratings" of school children are frequently discrepant,
      suggesting that use of subjective informant data via scale or interview does not
      form an objective basis for diagnosis of ADHD. Empiric diagnostic trials of
      stimulant medication that produce a behavioral response have been shown not to
      distinguish between children with and without "ADHD." In summary, the working
      dogma that ADHD is a disease or neurobehavioral condition does not at this time
      hold up to scrutiny of evidence. Thorough evaluation of symptomatic children
      should be individualized, and include assessment of educational, psychologic,
      psychiatric, and family needs.

PMID- 16417851
TI  - Aphasia owing to subcortical brain infarcts in childhood.
AB  - The aim of this study was to further define the clinical features of subcortical
      aphasia in children with deep brain infarcts and to define the sequelae
      associated with childhood strokes. We retrospectively studied nine children with
      left subcortical brain infarcts who presented with acquired language disorder and
      underwent language investigations based on standardized tests. Stroke in these
      patients involved the left internal capsule, lenticular or thalamic nuclei, or a
      combination of these. Early aphasic manifestations following the deep cerebral
      infarcts affected language expression. These included mutism, nonfluent speech,
      word finding difficulties, and phonemic and semantic paraphasia. Speech
      comprehension was generally more preserved. All patients subsequently improved,
      although variably; sequelae such as dysfluency, word finding difficulties, and
      written language learning impairment could be detected through standardized tests
      in six of them (all younger than 6 years at the time of the infarct). Two of the
      three remaining patients (both older than 6 years at the time of the infarct) had
      a full recovery. Our study confirms the concept of childhood subcortical aphasia,
      depicts the linguistic profile in these patients, and sustains the indication of
      systematic formal language assessment during the follow-up of all children with
      subcortical infarct involving the dominant hemisphere.

PMID- 16417853
TI  - Robert H.A. Haslam's fascinating autobiography.

PMID- 16417854
TI  - Diagnostic approach to cerebellar disease in children.
AB  - We reviewed the clinical records of 51 extensively investigated pediatric
      patients with structural abnormalities of the cerebellum as revealed by magnetic
      resonance imaging (MRI). Ten had hypoplasia of the vermis, 21 had hypoplasia of
      the vermis and cerebellar hemispheres, 2 had pontocerebellar hypoplasia, and 18
      had progressive cerebellar atrophy. A clear diagnosis was reached in 37 (72.5%).
      Initial characterization of the cerebellar alterations by MRI separated
      hypoplastic from atrophic cases and confirmed MRI as an essential preliminary
      means for distinguishing malformations from metabolic-degenerative conditions.
      However, the diagnostic possibilities are so numerous that it is not feasible to
      propose a standardized diagnostic protocol for pediatric patients with an altered
      cerebellum. Subsequent investigations should be suggested by the neuroradiologic
      and clinical peculiarities of each case.

PMID- 16417855
TI  - Quantitative analysis of cerebral cortical atrophy and correlation with clinical
      severity in unilateral Sturge-Weber syndrome.
AB  - Sturge-Weber syndrome is a neurocutaneous disorder with vascular malformations of
      the skin, brain, and eye. The objective of this study was to determine whether
      cortical atrophy in patients with Sturge-Weber syndrome correlates with clinical
      severity. Eighteen subjects (age 4 months-35 years) with unilateral Sturge-Weber
      syndrome received a neurologic examination and submitted previous magnetic
      resonance imaging (MRI) films. A blinded investigator assigned clinical severity
      scores based on seizures, hemiparesis, visual field cut, and cognitive
      impairments. Computer-aided analysis of MRIs produced laterality scores for
      cortical volume asymmetry. A significant relationship existed between clinical
      severity and laterality scores (Spearman's rho = -0.804; P < .001). Laterality
      scores also correlated well with hemiparesis subscores and weakly with cognitive
      impairment subscores (Kendall's tau b; P < .05). Using this simple, computer
      aided analysis, cortical volume asymmetry correlated with clinical status. This
      method offers the advantages of relative simplicity, objectivity, and wide
      applicability to films from outside institutions, as would be encountered in
      clinical practice.

PMID- 16417856
TI  - beta2-adrenergic receptor activation and genetic polymorphisms in autism: data
      from dizygotic twins.
AB  - Gestational and genetic factors can contribute to autism during infancy and early
      childhood through their effects on fetal brain development. Previous twin studies
      have shown strong genetic components for the development of autism, a disorder
      that can have multiple causes. We investigated the effects of prenatal
      overstimulation of the beta2-adrenergic receptor in dizygotic twins who were
      exposed to terbutaline, a selective beta2-adrenergic receptor agonist used to
      treat premature labor, as a gestational factor. As a possible genetic mechanism,
      we studied two beta2-adrenergic receptor polymorphisms in twins from whom DNA was
      available: glycine substitution at codon 16 (16G) and glutamic acid substitution
      at codon 27 (27E), which show diminished desensitization in vivo compared with
      the wild-type receptor. Continuous terbutaline exposure for 2 weeks or longer was
      associated with increased concordance for autism spectrum disorders in dizygotic
      twins (relative risk = 2.0), with a further increase in the risk for male twins
      with no other affected siblings (relative risk = 4.4). A significant association
      was found between the presence of 16G and 27E polymorphisms in autistic patients
      compared with population controls (P = .006). Prenatal overstimulation of the
      beta2-adrenergic receptor by terbutaline or by increased signaling of genetic
      polymorphisms of the beta2-adrenergic receptor that have diminished
      desensitization can affect cellular responses and developmental programs in the
      fetal brain, leading to autism.

PMID- 16417857
TI  - Finger cold-induced vasodilatation, sympathetic skin response, and R-R interval
      variation in patients with progressive spinal muscular atrophy.
AB  - To elucidate autonomic function in spinal muscular atrophy, we evaluated finger
      cold-induced vasodilatation, sympathetic skin response, and R-R interval
      variation in 10 patients with spinal muscular atrophy: 7 of type 1, 2 of type 2,
      and 1 of type 3. Results of finger cold-induced vasodilatation, sympathetic skin
      response, and R-R interval variation were compared with those of healthy
      children. Finger cold-induced vasodilatation was abnormal in 6 of 10 patients
      with spinal muscular atrophy; it was normal in the healthy children. The mean
      sympathetic skin response latency and amplitude did not differ significantly from
      those of the healthy children. Amplitudes of sympathetic skin response to sound
      stimulation were absent or low in all six patients with spinal muscular atrophy.
      No significant difference was found in the mean R-R interval variation of
      patients with spinal muscular atrophy and healthy children. Results show that
      some patients with spinal muscular atrophy have autonomic dysfunction, especially
      sympathetic nerve hyperactivity, that resembles dysfunction observed in
      amyotrophic lateral sclerosis.

PMID- 16417858
TI  - Identifying the primary epileptogenic hemisphere from electroencephalographic
      (EEG) and magnetoencephalographic dipole lateralizations in children with
      intractable epilepsy.
AB  - We used electroencephalographic (EEG) and magnetoencephalographic dipole
      lateralizations to identify the primary epileptogenic hemisphere in 41 children
      with intractable localization-related epilepsy. We compared EEG and
      magnetoencephalographic dipole lateralizations, EEG ictal onsets, and magnetic
      resonance images (MRIs). Concordant lateralization of EEG and
      magnetoencephalographic dipoles (> 50% of each lateralizing to the same
      hemisphere) occurred in 34 patients, with EEG ictal onsets in the same hemisphere
      in 23 (68%) and concordant MRI lesions in 23 (68%). Focal resection in 16 of 20
      patients resulted in a good surgical outcome. Of the seven children with
      nonconcordant magnetoencephalographic and EEG lateralizations, one (14%) had EEG
      ictal onset and one (14%) had MRI lesions that lateralized; none had surgery. The
      relationship between lateralized EEG and magnetoencephalographic dipoles
      forecasts surgical candidacy. Concordant lateralizations predict good seizure
      control after surgery by identifying the primary epileptogenic hemisphere.
      Discordant lateralizations signify an undetermined epileptogenic hemisphere and
      contraindicate surgery without further testing.

PMID- 16417859
TI  - Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term
      follow-up study.
AB  - This study aimed to evaluate the long-term efficacy and safety of topiramate in
      treating children with drug-resistant epilepsy. A multicentric, retrospective,
      open-label, add-on study was undertaken of 277 children (mean age 8.4 years;
      range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy
      was rated according to the seizure types and epilepsy syndrome. After a mean
      period of 27.5 months of treatment (range 24-61 months), 11 patients (4%) were
      seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The
      efficacy of topiramate treatment was noted in localization-related epilepsy and
      in generalized epilepsy. In addition, in a group of 114 patients, we compared the
      initial efficacy (evaluated after a mean of 9 months of follow-up) and the
      retention at a mean of 30 months of topiramate with regard to loss of efficacy
      (defined as the return to the baseline seizure frequency). Fifty-five (48%) of
      114 patients were initial responders. The retention at a mean of 30 months was 23
      of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of
      efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in
      patients with generalized epilepsy, such as symptomatic infantile spasms and
      Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a
      well-sustained topiramate efficacy was noted among patients with localization
      related epilepsy. Globally, adverse events were observed in 161 patients (58%)
      and were mainly represented by weight loss, hyperthermia, sedation, and
      nervousness, which, in most cases, disappeared after slowing titration or
      reducing the dosage of the drug. In conclusion, the present long-term study
      confirms that topiramate represents a useful drug effective in a wide range of
      seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that
      the efficacy of topiramate, when evaluated in the long-term perspective, is more
      sustained in localization-related epilepsy than in generalized epilepsy.

PMID- 16417860
TI  - Factors predictive of outcome in childhood epilepsy.
AB  - To identify early predictive factors of outcome in childhood epilepsy, the case
      records of all children with new-onset epilepsy presenting to a single neurology
      practice over a 10-year interval were reviewed. Only children with more than 2
      years of follow-up were included. Cox regression analysis was used to identify
      factors predictive of remission (successful cessation of medication). One hundred
      ninety-six children (mean age 7.6 +/- 3.7 years at first seizure, mean follow-up
      55 +/- 30 months) were identified. Ninety-eight of 196 children (50%) had an
      idiopathic epilepsy, 63 of 196 (32.1%) had cryptogenic epilepsy, and 35 of 196
      (17.9%) had remote symptomatic epilepsy. At final assessment, 52.6% were in
      remission, 12.8% had a poor outcome (recurrent seizures on therapeutic
      antiepileptic drug levels within 6 months prior to the final assessment), and
      6.9% were intractable (more than one seizure/month over 1 year with failure of
      three or more anticonvulsants). One year after initiating treatment, factors
      associated with a lower probability of remission included seizure recurrence in
      the 6- to 12-month interval after therapy initiation (hazard ratio 0.24),
      multiple seizure types (hazard ratio 0.40), and mental retardation at onset
      (hazard ratio 0.19). Factors predictive of a poor outcome included seizure
      recurrence in the 6- to 12-month interval after therapy initiation (odds ratio
      21.6), more than one seizure type (odds ratio 8.9), and global developmental
      delay at onset (odds ratio 8.9). Factors predictive of intractability included
      multiple seizure types (hazard ratio 6.5), mental retardation at onset (hazard
      ratio 7.2), and seizure recurrence in the first 6 to 12 months of treatment
      (hazard ratio 70). It appears that response in the first 6 to 12 months on
      antiepileptic medication is predictive of outcome. Clinical features of the
      underlying epilepsy and concurrent neurologic conditions were independently
      associated with intractability and a lower probability of remission.

PMID- 16417861
TI  - Where do families of children with epilepsy obtain their information?
AB  - A structured interview of 84 families of children with epilepsy followed through
      the neurology clinic of a tertiary care children's hospital was conducted to
      assess the epilepsy-specific information sources accessed and the perceived
      accuracy of these sources. Families accessed a mean of 3.5 sources from or
      specifically recommended by the clinic or family doctor and 4.1 sources outside
      these areas. Families of children with intractable epilepsy and higher-educated
      parents, but not those of higher socioeconomic status, consulted more
      extensively. The perceived accuracy of information rated highest for clinic
      recommended Internet sites (100%), the clinic nurse (97%), and the neurologist
      (93%). Sources external to the clinic had variable ratings; those with the
      greatest perceived accuracy included other Internet sites or family members
      within the medical profession (85% for both) and lay organizations (84%). Friends
      within the medical profession, other families, and complementary health care
      providers also ranked highly. Recommendation of sites and books by epilepsy
      clinics is more helpful than general handouts.

PMID- 16417862
TI  - Neuroradiologic findings in a young patient with characteristics of Sturge-Weber
      syndrome and Klippel-Trenaunay syndrome.
AB  - The patient presented here has extensive hemangiomata plana, especially on the
      right forehead, right upper eyelid, and right leg, as well as right leg
      hypertrophy and macrocephaly. Cerebral magnetic resonance imaging (MRI) showed
      abnormalities in only one occipital lobe consisting of focal cortical atrophy,
      leptomeningeal enhancement, and ipsilateral choroid plexus enlargement. Mental
      and motor development is normal, and he has no seizures. The parents are
      consanguineous. Leg hypertrophy associated with ipsilateral cutaneous vascular
      malformations is suggestive of Klippel-Trenaunay syndrome. The patient's central
      nervous system abnormalities on MRI and the hemangiomata plana on the ipsilateral
      upper eyelid and forehead point to Sturge-Weber syndrome. We conclude that the
      patient has an overlap syndrome between Klippel-Trenaunay syndrome and Sturge
      Weber syndrome.

PMID- 16417863
TI  - Cerebellar pilocytic astrocytoma with auditory presentation: case study.
AB  - An 8-year-old girl complained of decreased hearing and difficulty hearing from
      her right ear while on the telephone. Pure-tone and speech audiometry, immittance
      (tympanometry, acoustic reflex thresholds), auditory brainstem response, and
      transient click-evoked otoacoustic emissions were administered. The results were
      suggestive of a space-occupying lesion, and the patient was referred to a
      pediatric neurologist and neurosurgeon. A cerebellar pilocytic astrocytoma was
      found. The patient's audiologic profile is described, along with implications for
      pediatric neurologic evaluations.

PMID- 16417864
TI  - Case of Aicardi-Goutieres syndrome with long-lasting increase of cerebrospinal
      interferon-alpha.
AB  - Aicardi-Goutieres syndrome is a rare progressive encephalopathy characterized by
      a typical clinical picture, bilateral basal ganglia calcifications,
      leukodystrophy and brain atrophy, lymphocytosis, and elevated interferon-alpha in
      the cerebrospinal fluid. Among the cases described to date, variability in the
      clinical expression or in the cerebrospinal fluid abnormalities has been
      reported. We present a case with a delayed diagnosis at the age of 8 years, when
      brain computed tomography was done because there was no first image from the age
      of 8 months, when the disease started. Symmetric basal ganglia calcifications
      were visualized and led to purposeful investigation of the cerebrospinal fluid.
      It revealed an interferon-alpha titer of 103 IU/mL, which, together with the
      progressive brain damage and disease course, was crucial for the diagnosis. This
      rare finding of long-term highly elevated interferon-alpha in the cerebrospinal
      fluid is discussed with respect to the clinical course.

PMID- 16417865
TI  - Case of desmoplastic infantile ganglioglioma secreting ceruloplasmin.
AB  - Desmoplastic infantile ganglioglioma is a rare World Health Organization (WHO)
      grade I tumor commonly arising in early infancy and usually presenting with both
      solid and cystic components. We report a case of a large midline-enhancing
      desmoplastic infantile ganglioglioma in which newly formed cysts in communication
      with lateral ventricles contained highly proteinaceous fluid. Proteomic analysis
      of the fluid showed three proteins not normally found in cerebrospinal fluid.
      Immunohistochemical analysis of the tumor sample showed that the desmoplastic
      infantile ganglioglioma produced a high concentration of ceruloplasmin, which
      probably accounts for most of the 30- to 40-fold increase in protein compared
      with normal cerebrospinal fluid. To our knowledge, this is the first report of
      ceruloplasmin secretion by a brain tumor, and ongoing studies on the mechanism
      might yield novel approaches to reducing cyst production and protein content in
      an otherwise stable solid tumor.

PMID- 16417866
TI  - Hypomelanosis of Ito and Moyamoya disease.
AB  - Moyamoya disease is a cerebrovascular disease characterized by stenosis and
      occlusion of the arteries of the circle of Willis, with abnormal telangiectatic
      collateral circulation at the base of the brain. An association between moyamoya
      disease and neurofibromatosis 1, a neurocutanoeus disorder, is well established
      in the literature. However, its association with other neurocutaneous syndromes
      is infrequently reported. Hypomelanosis of Ito, another neurocutaneous syndrome,
      is characterized by macular hypopigmented skin whorls and variable neurologic
      involvement. Only one case study of an association between hypomelanosis of Ito
      and moyamoya disease has been reported in the English literature. We report a 17
      year-old girl with both hypomelanosis of Ito and angiographic moyamoya disease.
      She presented with intractable seizures, progressive left hemiparesis, and skin
      manifestations of hypomelanosis of Ito. Although one might consider a
      coincidental association, this second case points to an association between the
      two disorders. Detailed neuroimaging, in particular angiography, should be
      considered in children with hypomelanosis of Ito and abnormal neurologic
      findings.

PMID- 16417867
TI  - Hippocampal dysgenesis associated with temporal lobe hypoplasia and arachnoid
      cyst of the middle cranial fossa.
AB  - We describe two children with left hippocampal dysgenesis in association with
      temporal lobe hypoplasia and arachnoid cyst of the middle cranial fossa. The
      hippocampus showed an abnormal globular shape and blurred internal structure in
      both patients. One of the patients had juvenile myoclonic epilepsy without
      evidence of seizure onset in the abnormal temporal region. The other patient did
      not have epilepsy; however, he showed developmental language disorder with a
      probable relationship to the left temporal abnormalities.

PMID- 16417868
TI  - Answer to hypotonia: a simple hemogram.
AB  - A 1-year-old boy with weight loss, decreased activity, and psychomotor regression
      is presented. He was subjected to an extremely detailed evaluation, including
      electroencephalography (EEG) and magnetic resonance imaging (MRI), until a simple
      hemogram in our center revealed that he had macrocytic anemia with megaloblastic
      changes in the bone marrow. His history revealed that he had been exclusively
      breast-fed by his vegetarian mother. Further investigations showed low serum
      vitamin B12 concentration, methylmalonic aciduria, and homocysteinemia,
      indicating that the macrocytic anemia was due to vitamin B12 deficiency. This boy
      represents a case of macrocytic anemia and hypotonia owing to vitamin B12
      deficiency that developed because of exclusive breast-feeding by a vegetarian
      mother.

PMID- 16417869
TI  - Ratio of motor seizure components in childhood temporal lobe epilepsy.

PMID- 16417871
TI  - N. Paul Rosman, MD: scholar, teacher, clinician, and humanist.

PMID- 16417872
TI  - Association of Duchenne muscular dystrophy with autism spectrum disorder.
AB  - We hypothesize that Duchenne muscular dystrophy and autism spectrum
      disorder/pervasive developmental disorder co-occur with a greater than random
      frequency. In this study, we set out to reject the hypothesis that Duchenne
      muscular dystrophy and autism spectrum disorder/pervasive developmental disorder
      co-occur no more often than expected by chance. Two index cases and six
      additional boys with concomitant Duchenne muscular dystrophy and autism spectrum
      disorder were identified in a muscular dystrophy clinic that approximates the
      total number of Duchenne muscular dystrophy boys (158) in the state of
      Massachusetts. The rate of prevalence (6 of 158) was compared with the prevalence
      rate of autism spectrum disorder in boys in the general population (1.6 in
      1,000). We rejected the hypothesis that Duchenne muscular dystrophy and autism
      spectrum disorder co-occurrence was likely to be explained by chance (P = .006).
      We identify a previously unrecognized association of Duchenne muscular dystrophy
      with autism spectrum disorder. Further work might elucidate the level of
      association between these two conditions, either at the genetic or at the protein
      level, and might clarify, at least partially, the neurobiologic mechanisms
      associated with autism spectrum disorder.

PMID- 16417873
TI  - Environmental enrichment reverses the impaired exploratory behavior and altered
      gene expression induced by early-life seizures.
AB  - Behavioral problems, school failure, and memory impairment are common among
      children with epilepsy. Currently, no effective treatment exists to promote
      recovery and neuron regeneration after seizures. To investigate the efficacy of
      environmental enrichment in reversing early-life seizure-induced changes in
      exploratory behavior and gene expression, we injected postnatal day 20 to 25 rats
      with kainic acid or saline and placed them either singly in a cage or as a group
      of eight in an enriched environment for 7 to 10 days. Exploratory behavior was
      quantified in an open field, and hippocampal gene analysis was performed on
      oligonucleotide microarrays. Exploratory behavior in kainic acid isolated rats
      were decreased in open field, whereas kainic acid rats exposed to an enriched
      environment behaved similarly to controls (n = 37, analysis of variance, P <
      .001). Correlated with an improvement in behavior, genes involved in synaptic
      plasticity and memory consolidation, such as Arc, Homer1a, and Egr1, were
      significantly increased in rats exposed to environmental enrichment. Real-time
      quantitative reverse transcriptase-polymerase chain reaction confirmed our
      microarray data on select genes. Our results provide an experimental basis for
      promoting enriching education programs for children with epilepsy.

PMID- 16417874
TI  - The floppy infant: retrospective analysis of clinical experience (1990-2000) in a
      tertiary care facility.
AB  - We describe the results of a retrospective study of floppy infants evaluated at
      the Children's Hospital of Winnipeg, a tertiary care children's facility. Cases
      were ascertained by a systematic search of clinical databases, hospital and
      electromyographic records for "floppy" infants age < 1 year, referred over a
      period of 11 years (1990-2000). Eighty-nine infants, 42 female (47.2%) and 47
      male (52.8%), were included in the study. A definitive diagnosis was established
      in 60 (67.4%) cases, in 24 cases (40%) on purely clinical grounds, whereas in 36
      (60%) cases, additional investigations were necessary. Karyotype, molecular
      diagnostics, cranial imaging, and muscle and skin biopsy provided diagnostic
      information. Genetic disorders in 18 of 60 (20.2%), congenital or acquired
      disorders of the central nervous system in 22 of 60 (24.7%), and disorders of the
      lower motor unit in 9 of 60 (10.1%) contributed to the majority of diagnoses.
      Eight of 89 (8.9%) infants died in the first year, and 2 of 89 (2.6%) were on
      home ventilation. Of the 61 infants surviving beyond 12 months, 38 of 61 (62.3%)
      were found to be globally delayed, and only 30 of 61 (49.2%) achieved independent
      ambulation at their last clinical evaluation. Systematic evaluation of a floppy
      infant followed by careful selection of investigations (karyotype, DNA-based
      diagnostic tests, and cranial imaging) can maximize diagnostic yield.

PMID- 16417875
TI  - Serial headache drawings by children with migraine: correlation with clinical
      headache status.
AB  - Children's artistic self-depictions of headache provide valuable insights into
      their experience of pain and aid in the diagnostic differentiation of headache
      types. In a previous study, we compared the clinical diagnosis (gold standard)
      and artistic diagnosis of headaches in 226 children. In approximately 90% of
      cases, the drawing predicted the clinical diagnosis of migraine versus
      nonmigraine headache correctly. In the present study, we explored whether
      headache drawings correlate with clinical improvement after treatment in children
      with migraine headaches followed longitudinally. Children seen in the Pediatric
      Neurology Clinic with the chief complaint of headache were asked to draw a
      picture of what their headache feels like. On subsequent clinic visits, children
      with the clinical diagnosis of migraine were asked to draw another picture
      depicting their current headache. The two drawings were compared to assess
      whether there was improvement; this "artistic response" was then correlated with
      the child's clinical status (ie, whether the headaches were improved clinically).
      One hundred eleven children (66 girls, 45 boys) participated in the study, with a
      mean interval of 5.3 +/- 2.3 (standard error of the mean) months between the
      first and second visits. The mean age at the first visit was 11.6 +/- 3.1 years.
      The raters agreed that serial drawings were both improved or both not improved in
      99 of the 111 cases (89%; interrater reliability kappa score of 0.767). Fifty
      three children had improvements in their headaches and drawings, 3 children had
      an improved drawing but no clinical headache improvement, 32 children had no
      improvement in either their drawing or clinical headaches, and 11 children had
      improved headaches but no improvement in their drawing. The sensitivity of the
      drawings for clinical improvement was 0.83, and the specificity was 0.91. The
      predictive value of an improved headache drawing for an improved clinical
      response was 0.946. There was no correlation between specific treatment modality
      and artistic response. We concluded that children's headache drawings are a
      useful adjunct for the diagnosis of headache type and provide valuable insights
      into their experience of pain. The present data show that headache drawings can
      be used longitudinally to provide additional information about the clinical
      course. The technique is simple, inexpensive, and enjoyable for children and can
      be applied in a variety of clinical settings.

PMID- 16417876
TI  - Novel form of intermediate salla disease: clinical and neuroimaging features.
AB  - The objective of this article is to describe the clinical, radiographic, and
      molecular genetic features of a new intermediate form of free sialic storage
      disease. Free sialic storage disease is a rare autosomal recessive lysosomal
      disorder that results from mutations in SLC17A5, a gene that codes for sialin, a
      lysosomal membrane sialic acid transporting protein. Infantile sialic acid
      storage disease has a severe phenotype, and Salla disease (Finnish variant) is
      generally milder in phenotype; intermediate forms have also been described. There
      have been few reports of magnetic resonance imaging (MRI) in the sialic acid
      storage disorders; leukodystrophy has been the characteristic finding, along with
      hypoplasia of the corpus callosum. An 8-month-old non-Finnish child presented
      with hypotonia and global developmental delay. Serial MRIs with magnetic
      resonance spectroscopy at 9 and 16 months revealed severe hypomyelination and
      hypogenesis of the corpus callosum. There was mild elevation of urinary sialic
      acid (4.5 times above normal). Electron microscopy of a skin biopsy showed
      lysosomal enlargement with oligosaccharide storage, and confirmatory molecular
      genetic testing revealed compound heterozygosity for two new SLC17A5 mutations.
      Free sialic storage disease of the intermediate type is an important part of the
      differential diagnosis of a hypotonic, delayed child with abnormal white matter
      on MRI. Intermediate types of free sialic acid overlap in phenotype with
      infantile sialic acid storage disease and the milder Salla disease and thus might
      be more difficult to identify clinically; the lack of Finnish ethnicity should
      not preclude testing for this probably under-recognized disorder. White-matter
      abnormalities appear to be characteristic of the entire phenotypic spectrum.

PMID- 16417877
TI  - Novel motor and somatosensory activity is associated with increased cerebral
      cortical blood volume measured by near-infrared optical topography.
AB  - Recent reports suggest that learning is enhanced by emotion, spontaneity, and
      play. The mechanisms of this enhancement are unclear and might involve increased
      cortical stimulation by the limbic system. Since neuronal activity is tightly
      coupled to changes in cerebral blood flow and volume, the demonstration of
      increased cortical blood volume during playful versus routine motor and
      somatosensory activity would imply enhanced neuronal activity and provide insight
      into the complex interaction between play and learning. Near-infrared
      spectroscopy was used to detect changes in cortical blood volume during
      performance of (1) rudimentary visual, motor, and speech tasks; (2) integration
      of the tasks in a familiar routine manner; and (3) integration of the tasks in a
      novel, spontaneous, playful manner. No significant differences in cortical blood
      volume were found during the performance of the individual rudimentary tasks and
      their routine integration. However, the novel integration activity was associated
      with a significantly greater increase in frontal lobe oxyhemoglobin,
      deoxyhemoglobin, and total hemoglobin, as well as parietal lobe total hemoglobin.
      This small pilot study provides a limited measure of physiologic support for a
      relationship between play and learning.

PMID- 16417878
TI  - Tau, phospho-tau, and S-100B in the cerebrospinal fluid of children with multiple
      sclerosis.
AB  - Axonal injury and glial activation are an early neuropathologic event in adults
      with multiple sclerosis. To investigate whether markers of axonal injury and
      glial activation are already elevated in the cerebrospinal fluid of children with
      multiple sclerosis, we studied the cerebrospinal fluid of 25 children with
      multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S
      100B proteins using specific enzyme-linked immunoabsorbent assays. In general,
      tau, phospho-tau, and S-100B protein levels did not differ significantly between
      groups. However, in a subgroup of nine children with multiple sclerosis, all of
      whom had prominent clinical symptoms at the time of lumbar puncture and
      radiologic disease activity, tau protein levels were significantly elevated when
      compared with other controls. These data indicate that axonal injury is not
      restricted to adult multiple sclerosis but can already occur in children with
      multiple sclerosis.

PMID- 16417879
TI  - Krabbe disease: severe neonatal presentation with a family history of multiple
      sclerosis.
AB  - Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal
      recessive disorder caused by a deficiency of a lysosomal enzyme,
      galactocerebrosidase. This defect prevents normal turnover of the galactolipids
      and results in progressive demyelination. In the infantile form, symptoms
      typically present at 3 to 6 months of age with subsequent neurologic
      deterioration. We report a case with presentation on day 7 of life and rapid
      progression culminating in death at 10 weeks. Galactocerebrosidase activity was
      absent in the leukocytes, and a 30 kb deletion in the GALC gene was found. To our
      knowledge, this is the earliest reported death from Krabbe disease. Several
      family members have multiple sclerosis, which is also a demyelinating disorder.
      We propose that the neonatal expression could be an example of complementary gene
      interaction in which coinheritance of a predisposition to multiple sclerosis led
      to the unusual early manifestation and rapid course of Krabbe disease in this
      infant.

PMID- 16417881
TI  - Sydenham's chorea: positron emission tomographic (PET) scan studies.
AB  - Two patients with Sydenham's chorea were evaluated with positron emission
      tomographic (PET) scans in the active phase of the disease. One patient had
      repeat scanning in the recovery phase. PET scans showed hypermetabolic changes of
      the caudate nuclei and putamen in the active phase of Sydenham's chorea. The scan
      reverted to normal in the recovery phase. These changes can afford a basis for
      comparing concurrent serum antibody studies in the acute and recovery phases of
      Sydenham's chorea.

PMID- 16417880
TI  - Video and CD-ROM as a training tool for performing neurologic examinations of 1
      year-old children in a multicenter epidemiologic study.
AB  - In lieu of traditional training of examiners to identify cerebral palsy on a
      neurologic examination at age 1 year, we proposed an alternative approach using a
      multimedia training video and CD-ROM we developed after a two-step validation
      process. We hypothesized that use of CD-ROM interactive training will lead to
      reliable and valid performance of the neurologic examination by both pediatric
      neurologists and nonpediatric neurologists. All examiners were asked to take one
      of six interobserver variability tests found on the CD-ROM on two occasions. In
      the first interobserver variability evaluation, 89% (531 of 594) of the responses
      agreed with the gold standard responses. Following annotated feedback to the
      examiners about the two items that had a 60% correct rate, the correct response
      rate rose to 93% (114 of 123). In the second interobserver variability
      evaluation, 88% (493 of 560) of the responses agreed with the gold standard
      responses. Following annotated feedback to the examiners about the four items
      that had a 70% correct rate, the correct response rate rose to 96% (104 of 108).
      Interactive CD-ROM examination training is an efficient and cost-effective means
      of training both neurologists and non-neurologists to perform structured
      neurologic examinations in 1-year-old children. It provides an effective means to
      evaluate interobserver variability, offers a route for feedback, and creates an
      opportunity to reevaluate variability, both immediately and at periodic
      intervals.

PMID- 16417882
TI  - Postictal paresis in children with benign rolandic epilepsy.
AB  - Following a search for the presence of postictal paresis in a cohort of 70
      patients with benign rolandic epilepsy of childhood, the symptomatology of the
      seizures and the presence of postictal paresis were reviewed. All children
      underwent a neurologic evaluation, including electroencephalography (EEG) and
      neuroimaging. Eight of the 70 patients (3 girls and 5 boys) were found to have
      postictal paresis. All patients had partial motor seizures involving
      predominantly the upper extremities and, to a lesser degree, the face and lower
      extremities. In all eight patients, the motor deficits resolved within 60
      minutes. Follow-up neurologic examination was nonfocal in all patients. Seven of
      the eight patients experienced postictal paresis once, and one patient had two
      such episodes. Three of the eight patients experienced a brief speech arrest. The
      EEG in all patients demonstrated centrotemporal sharp waves. In seven patients,
      the sharp waves were bilateral and independent, and in one patient, the rolandic
      sharp waves were unilateral. A horizontal dipole with positivity at the central
      region was found in all patients using an average montage. In conclusion, we
      found an 11.5% association of postictal paresis in children with benign rolandic
      epilepsy of childhood, whereas 38% of children also had a brief speech arrest.
      The EEG was characteristic for benign rolandic epilepsy of childhood with
      bilateral asynchronous discharges in seven of eight patients (83%) and the
      presence of dipole in all patients. The presence of postictal paresis should not
      exclude the diagnosis of benign rolandic epilepsy of childhood.

PMID- 16417883
TI  - Prognostic significance of tuber count and location in tuberous sclerosis
      complex.
AB  - The objectives of this study were (1) to test the utility of tuber count and
      tuber location as biomarkers of disease severity in patients with tuberous
      sclerosis complex and (2) to examine the relationship between gene mutation,
      tuber count, and tuber location. We found that an increased tuber count per lobe
      and in total was associated with an increased risk of infantile spasms (P < .01).
      Increased tuber count in the occipital lobe was associated with an increased risk
      of pervasive developmental disorder (P = .0074). The mean tuber count per lobe
      and in total was higher in those with poorly controlled seizures and those with
      off-track development; however, these differences were not statistically
      significant (P > .01). The TSC2 gene mutation was associated with a significant
      increase in the tuber count per lobe and in total (P < .01). In summary,
      increased tuber count is strongly associated with infantile spasms and a TSC2
      gene mutation. Seizure control and developmental delay do not show the strong
      association with tuber count suggested by the earlier literature.

PMID- 16417884
TI  - Magnetic resonance imaging study of brain asymmetries in dyslexic patients.
AB  - Research studies suggest that the left hemisphere is involved in the
      pathophysiology of dyslexia. Thus far, the exact location and nature of the
      purported lesion(s) remain a matter of contention. The present study describes
      the distribution of structural abnormalities as related to brain symmetry in the
      brains of dyslexic individuals. High-resolution three-dimensional magnetic
      resonance images (MRIs) were analyzed in 16 dyslexic men and 14 controls matched
      for sex, age, educational level, and handedness. A computerized image analysis
      system was used to assess the volumetric deformations required to match each
      brain with its left-right mirror image. The results showed significant
      abnormalities in five left hemisphere structures involving the extrapyramidal and
      limbic systems: amygdala, hippocampus proper, parahippocampal gyrus, putamen, and
      globus pallidus. The left hemisphere is thought to play a major role in the
      temporal analysis of information. This stream of temporal analysis is of
      importance in motor movements. Reading might have evolved as an exaptation to
      motor movements requiring the sequential analysis of information.

PMID- 16417885
TI  - Serum insulin, leptin, and neuropeptide y levels in epileptic children treated
      with valproate.
AB  - Weight gain is a common side effect of valproate treatment. The potential
      mechanisms of valproate-associated weight gain are not yet clear. Decreased blood
      glucose level, impairment of beta-oxidation of fatty acids, and increased insulin
      levels are some of the possible mechanisms. The aim of the present study is to
      evaluate the role of insulin, leptin, and neuropeptide Y in valproate-related
      weight gain in epileptic children. In 20 epileptic children treated with
      valproate before treatment and after a follow-up period of 3 and 6 months, body
      mass index and fasting insulin glucose ratio were calculated and serum glucose,
      insulin, cortisol, leptin, and neuropeptide Y levels were measured. At the end of
      3 months, the mean body mass index values and the mean serum insulin, fasting
      insulin glucose ratio, and neuropeptide Y levels increased, whereas the serum
      glucose levels decreased. After 6 months of treatment, the mean serum cortisol
      and leptin levels were high, in addition to the body mass index, neuropeptide Y,
      and fasting insulin glucose ratio. These results suggest that weight gain during
      valproate treatment might be related to low glucose and high insulin, cortisol,
      leptin, and neuropeptide Y levels.

PMID- 16417886
TI  - X-linked MCT8 gene mutations: characterization of the pediatric neurologic
      phenotype.
AB  - We report a family with X-linked mental retardation that has a novel mutation in
      the monocarboxylate transporter 8 (MCT8) gene associated with a characteristic
      neurodevelopmental phenotype with early childhood hypotonia that progresses to
      spasticity and global developmental delays. Affected patients experience moderate
      to severe psychomotor delays and congenital hypotonia, develop a myopathic
      facies, have diminished muscle bulk and generalized muscle weakness, develop
      progressive spasticity and movement disorders, and have limited speech but alert,
      affable personalities. Acquired microcephaly and abnormal myelination on brain
      magnetic resonance imaging can be present. Normal monocarboxylate transporter 8
      gene functioning appears to be necessary for normal thyroid-associated metabolism
      in neurons. Abnormal thyroid function tests appear to be a consistent finding in
      the absence of typical signs of thyroid dysfunction. Although the phenotype
      appears to be consistent, and although the neurotoxic effects of abnormal central
      and peripheral neuromuscular system thyroid metabolism might be partly or wholly
      responsible for the neurologic phenotype reported, the exact mechanism remains
      unclear.

PMID- 16417901
TI  - Misconceptions regarding case-control studies of bicycle helmets and head injury.
AB  - A number of published case-control studies have reported that bicycle helmets are
      associated with a reduced risk of head injury and brain injury among bicyclists
      who crashed. A paper in this journal offered several criticisms of these studies
      and of a systematic review of these studies. Many of those criticisms stem from
      misconceptions about the studies that have been done and about case-control
      studies in general. In this manuscript we review case-control study design,
      particularly as it applies to bicycle helmet studies, and review some aspects of
      the analysis of case-control data.

PMID- 16417902
TI  - Myocardial proteases and matrix remodeling in inflammatory heart disease.
AB  - Recently, it has been demonstrated that myocardial inflammation plays a pivotal
      role in the development and progression of congestive heart failure. The
      myocardial inflammatory reaction not only affects myocardial hypertrophy and
      apoptosis, but it has a major influence on the regulation of extracellular matrix
      turnover. The balance between collagen synthesis and degradation is of crucial
      relevance in maintaining the structural integrity of the heart. Therefore, the
      overwhelming inflammatory response, as seen in acute myocarditis or inflammatory
      cardiomyopathy, could lead to a breakdown of this tightly regulated system. This
      is an additional key factor in the development and progression of heart failure.
      This review summarizes the importance of myocardial inflammation in respect to
      extracellular matrix remodeling and its possible patho-physiological role in the
      development and progression of left ventricular dysfunction in inflammatory heart
      disease.

PMID- 16417903
TI  - Lipid monolayers on Hg as a valid experimental model for lipid membranes under
      electrical fields.
AB  - Monolayers spread on Hg drops are shown as a suitable experimental set up to
      study the influence of external electric fields on the structure of lipid
      membranes. The electrical response exhibits a sharp transition at 24 degrees C,
      the transition temperature of DMPC. In addition, voltammetric response of
      monolayers of mixtures of DMPC/DMPE adsorbed on mercury, shows a similar trend to
      that found for dipole potential of monolayers of the same composition spread on
      an air-solution interface. It is concluded that a lipid monolayer adsorbed in a
      mercury-solution interface, has comparable properties as those found in other
      experimental models of lipid membranes in similar conditions. In addition, they
      constitute an ideal set up to study the effect of electrical fields on the
      dynamic conformation of lipids as a function of packing change produced by the
      condensation in the gel state or by the interaction of polar head groups.

PMID- 16417904
TI  - Myeloperoxidase-derived 2-chlorohexadecanal forms Schiff bases with primary
      amines of ethanolamine glycerophospholipids and lysine.
AB  - Numerous studies have suggested relationships between myeloperoxidase,
      inflammation, and atherosclerosis. MPO-derived reactive chlorinating species
      (RCS) attack membrane plasmalogens releasing alpha-chloro-fatty aldehydes (alpha
      Cl-FALDs) including 2-chlorohexadecanal (2-ClHDA). The molecular targets of alpha
      Cl-FALDs are not known. The current study demonstrates 2-ClHDA adducts with
      ethanolamine glycerophospholipids and Fmoc-lysine. Utilizing electrospray
      ionization mass spectrometry, chlorinated adducts were observed that are apparent
      Schiff base adducts. Reduction of these Schiff base adducts with sodium
      cyanoborohydride resulted in a novel, stable adduct produced by the elimination
      of HCl. NMR further confirmed this structure. 2-ClHDA adducts with ethanolamine
      glycerophospholipids were also substrates for phospholipase D (PLD). The
      hydrolysis products were derivatized to pentafluorobenzoyl esters, and further
      structurally confirmed by GC-MS. Multiple molecular species of 2-ClHDA-N-modified
      ethanolamine glycerophospholipids were observed in endothelial cells treated with
      2-ClHDA. These results show novel Schiff base adducts of alpha-Cl-FALDs with
      primary amines, which may represent an important fate of alpha-Cl-FALDs.

PMID- 16417905
TI  - Treatment of subtrochanteric nonunions.
AB  - The purpose of this retrospective study was to evaluate our results of treating
      subtrochanteric nonunions with a (AO/ASIF) blade plate. We treated a total of 32
      patients (33 hips) with a subtrochanteric nonunion with a blade plate. Outcome
      measures were time to healing, complications after the index-operation and the
      Merle d'Aubigne hip score at follow-up. Union was achieved in 32 of the 33 hips
      after an average of 5 months. Complications were seen in nine patients (nine
      hips); five complications required re-intervention and four minor complications
      were treated conservatively. According to the Merle d'Aubigne hip score, 10
      patients were rated as excellent, 15 as good and 7 as fair. This study shows that
      treatment of a subtrochanteric nonunion with a blade plate consistently leads to
      bony union with a good to excellent hip score in the vast majority of the
      patients (25 out of 33 hips).

PMID- 16417906
TI  - Temporary vertical transarticular-pin fixation of unstable ankle fractures with
      critical soft tissue conditions.
AB  - Unstable ankle fractures are demanding injuries to treat. Open reduction and
      internal fixation are accepted as standard care, however, in patients with severe
      soft tissue damage or serious medical conditions, this approach may not always be
      advisable. Closed reduction with temporary fixation using vertical transarticular
      pins is one method to maintain joint alignment until an open technique is
      possible. Fourteen patients (median age: 59.5 years) with unstable ankle
      fractures, including three type-2 open fractures, were included in the study.
      Open reduction and fixation was delayed because of severe soft tissue damage, and
      a temporary transarticular pin fixation using two Kirschner wires was performed.
      After a median of 8.4 days, an open reduction and internal fixation was carried
      out in all patients. No complications related to the temporary arthrodesis were
      observed during the acute phase, and follow-up at 24 months revealed no damage to
      the articular surface attributable to the pin insertion. The median Olerud-score
      was 33.43, but three patients showed signs of early post-traumatic arthritis
      which we felt were due to the initial fracture. We conclude that closed reduction
      and temporary fixation using vertical transarticular pins of unstable ankle
      fractures is a safe method of maintaining joint alignment until a definitive open
      approach is feasible.

PMID- 16417908
TI  - Different response requirements for IFNgamma production in ELISPOT assays by CD4+
      T cells from mice early and late after immunization.
AB  - Antigen specific immune responses that occur early after antigen exposure differ
      from those that are present late in the response. The present study focused on
      detecting changes in production of IFNgamma by CD4+ T cells over time during
      chronic antigen exposure. (C3HxCB17)F1 mice were primed with recombinant
      hepatitis B core antigen (rHBcAg) in incomplete Freund's adjuvant to allow
      persistent antigen exposure. To assay the CD4+ T cell response to HBcAg,
      splenocytes from immunized mice were restimulated with rHBcAg for 24 or 48 h in
      vitro and tested for IFNgamma and IL-5 secreting cells by ELISPOT. Results showed
      that early after antigen exposure (7 days for primary and 3 days for secondary
      exposures), the maximal number of IFNgamma secreting cells was detected in the
      ELISPOT after 24 h of restimulation. However, late after antigen exposure (28
      days for primary and 14 days for secondary exposures), the maximum number of
      IFNgamma secreting cells was not detected until 48 h of restimulation in this
      assay. This delay in IFNgamma production was related to the availability of IL-2,
      since addition of IL-2 allowed the delayed cells from late responses to develop
      peak IFNgamma production in vitro by 24 h, equivalent to that of cells from early
      responses. This IL-2 dependent delay occurred in Th1-type IFNgamma responses but
      not in Th2-type IL-5 responses. These observations indicate that, when detecting
      IFNgamma secreting cells it is important to screen responses at different times
      of restimulation or in the presence and absence of IL-2 to ensure optimal
      detection. This approach should prove critical, particularly when evaluating
      patients with chronic infections and in determining the effectiveness of vaccines
      since these deal with both early and late responses.

PMID- 16417907
TI  - Inherited thrombophilia in recurrent spontaneous abortion among Chinese women.

PMID- 16417909
TI  - Delayed activation of DNA damage checkpoint and radiation-induced genomic
      instability.
AB  - Ionizing radiation induces genomic instability, transmitted over many generations
      through the progeny of surviving cells. It is manifested as the expression of
      delayed effects such as delayed cell death, delayed chromosomal instability and
      delayed mutagenesis. Induced genomic instability exerts its delayed effects for
      prolonged periods of time, suggesting the presence of a mechanism by which the
      initial DNA damage in the surviving cells is memorized. Our recent studies have
      shown that transmitted memory causes delayed DNA breakage, which in turn
      activates DNA damage checkpoint, and is involved in delayed manifestation of
      genomic instability. Although the mechanism(s) involved in DNA damage memory
      remain to be determined, we suggest that ionizing radiation-induced mega-base
      deletion destabilizes chromatin structure, which can be transmitted many
      generations through the progeny, and is involved in initiation and perpetuation
      of genomic instability. The possible involvement of delayed activation of a DNA
      damage checkpoint in the delayed induction of genomic instability in bystander
      cells is also discussed.

PMID- 16417910
TI  - A systems biology approach to multicellular and multi-generational radiation
      responses.
AB  - Recent studies have highlighted crosstalk between irradiated cells and non
      irradiated bystander cells and have uncovered high-frequency phenotypes of
      genomic instability in the progeny of irradiated cells that cannot be solely
      explained by radiation-induced mutation. It is difficult to explain these
      multicellular and multi-generational phenomena using the current paradigm of
      radiation biology. Radiation-induced bystander effect is a type of multicellular
      response to radiation that illustrates that the unit of function in multicellular
      organisms is neither the genome nor the cell. Cell function in complex three
      dimensional tissues is coordinated by soluble signaling peptides and by small
      molecules within the context of insoluble scaffolding provided by the
      extracellular matrix. Adaptive response and radiation-induced genomic instability
      could thus result from persistent signaling perturbations following radiation
      exposures. A model of radiation response based on the systems biology principles
      of network interconnectivity and spatial organization should reconcile the
      apparent contradiction of these cellular phenotypes within the higher order
      structure of tissues and organisms.

PMID- 16417911
TI  - Radiation-induced genomic instability is associated with DNA methylation changes
      in cultured human keratinocytes.
AB  - The mechanism by which radiation-induced genomic instability is initiated,
      propagated and effected is currently under intense scrutiny. We have investigated
      the potential role of altered genomic methylation patterns in the cellular
      response to irradiation and have found evidence for widespread dysregulation of
      CpG methylation persisting up to 20 population doublings post-irradiation.
      Similar effects are seen with cells treated with medium from irradiated cells
      (the 'bystander effect') rather than subjected to direct irradiation. Using an
      arbitrarily primed methylation sensitive PCR screening method we have
      demonstrated that irradiation causes reproducible alterations in the methylation
      profile of a human keratinocyte cell line, HPV-G, and have further characterised
      one of these sequences as being a member of a retrotransposon element derived
      sequence family on chromosome 7; MLT1A. Multiple changes were also detected in
      the screen, which indicate that although the response of cells is predominantly
      hypermethylation, specific hypomethylation occurs as well. Sequence specific
      changes are also reported in the methylation of the pericentromeric SAT2
      satellite sequence. This is the first demonstration that irradiation results in
      the induction of heritable methylation changes in mammalian cells, and provides a
      link between the various non-radiological instigators of genomic instability, the
      perpetuation of the unstable state and several of its manifestations.

PMID- 16417912
TI  - Thiodiglycol, the hydrolysis product of sulfur mustard: analysis of in vitro
      biotransformation by mammalian alcohol dehydrogenases using nuclear magnetic
      resonance.
AB  - Thiodiglycol (2,2'-bis-hydroxyethylsulfide, TDG), the hydrolysis product of the
      chemical warfare agent sulfur mustard, has been implicated in the toxicity of
      sulfur mustard through the inhibition of protein phosphatases in mouse liver
      cytosol. The absence of any inhibitory activity when TDG was present in assays of
      pure enzymes, however, led us to investigate the possibility for metabolic
      activation of TDG to inhibitory compound(s) by cytosolic enzymes. We have
      successfully shown that mammalian alcohol dehydrogenases (ADH) rapidly oxidize
      TDG in vitro, but the classic spectrophotometric techniques for following this
      reaction provided no information on the identity of TDG intermediates and
      products. The use of proton NMR to monitor the oxidative reaction with structural
      confirmation by independent synthesis allowed us to establish the ultimate
      product, 2-hydroxyethylthioacetic acid, and to identify an intermediate
      equilibrium mixture consisting of 2-hydroxyethylthioacetaldehyde, 2
      hydroxyethylthioacetaldehyde hydrate and the cyclic 1,4-oxathian-2-ol. The
      intermediate nature of this mixture was determined spectrophotometrically when it
      was shown to drive the production of NADH when added to ADH and NAD.

PMID- 16417913
TI  - A cost analysis of the treatment of patients with post-thrombotic syndrome in
      Brazil.
AB  - INTRODUCTION: Post-thrombotic syndrome (PTS) occurs in 15-50% of patients with
      deep vein thrombosis (DVT), and is associated with substantial medical costs.
      This prospective observational study investigated the costs associated with the
      treatment of PTS in Brazil. MATERIALS AND METHODS: A total of 157 patients
      diagnosed with PTS and with a history of DVT were recruited from nine centers in
      Brazil. The costs of investigations and treatment for PTS over a 1-year follow-up
      period were analyzed. Ninety patients were available for this analysis. RESULTS:
      Of the 90 patients, 17 had mild-to-moderate PTS, and 73 had severe PTS. The
      patients with severe PTS tended to undergo more investigations and
      hospitalizations for PTS than those with mild-to-moderate PTS, although the
      differences between the two groups did not reach statistical significance. The
      mean annual cost of treating PTS in Brazilian Reais was 1214 R dollars (426 US
      dollars) for mild-to-moderate PTS and 3386 R dollars (1188 US dollars) for severe
      PTS. The difference was mainly due to significantly higher hospitalization costs
      in patients with severe PTS (704 R dollars/247 US dollars vs. 0 R dollars;
      p=0.044). CONCLUSION: These results suggest that PTS imposes substantial demands
      on health care resources in Brazil. The implementation of effective
      thromboprophylactic strategies could significantly reduce the incidence of DVT,
      and hence of PTS, potentially resulting in significant cost savings.

PMID- 16417915
TI  - Variation in surface topography of different NiTi orthodontic archwires in
      various commercial fluoride-containing environments.
AB  - OBJECTIVES: The surface topography can affect the friction behavior between an
      orthodontic wire and brackets during clinical applications. The purpose of this
      study was to investigate the influence of a fluoride-containing environment on
      the surface topography variations of different nickel-titanium (NiTi) orthodontic
      archwires. METHODS: Four different NiTi commercial orthodontic archwires were
      immersed in fluoride mouthwashes and in artificial saliva with the addition of
      commercial fluoride toothpastes or prophylactic gels for a 28-day period. Atomic
      force microscopy (AFM) was used to measure the three-dimensional surface
      topography of NiTi archwires before and after the immersion tests. Two-way
      analysis of variance (ANOVA) was used to analyze the surface roughness variance
      (including DeltaR(a), DeltaR(ms), and DeltaR(z)) with the archwire manufacturer
      and immersion test environment as the factors. RESULTS: Both the archwire
      manufacturer and immersion environment had a significant influence on DeltaR(a),
      DeltaR(ms), and DeltaR(z) (manufacturer: P<0.05; environment: P<0.0001).
      Regardless of the archwire manufacturer, no statistically significant difference
      in DeltaR(a) (<70 nm), DeltaR(ms) (<90 nm), and DeltaR(z) (<450 nm) was observed
      on the tested NiTi archwires in lower fluoride-containing (<2500 ppm)
      environments, including the various fluoride mouthwashes and the artificial
      saliva added with fluoride toothpastes. In artificial saliva added with high
      fluoride prophylactic gel (around 17,000 ppm), a significant increase in
      DeltaR(a) (around 120-250 nm), DeltaR(ms) (around 140-320 nm), and DeltaR(z)
      (around 770-1410 nm), i.e. increasing the surface roughness, was observed on the
      tested NiTi archwires. SIGNIFICANCE: The variation in the surface topography of
      the NiTi orthodontic archwires in the commercial fluoride-containing environments
      should be taken into consideration when the friction between the archwire and
      bracket is a clinical concern.

PMID- 16417917
TI  - Microencapsulation of alpha-tocopherol using sodium alginate and its controlled
      release properties.
AB  - Response surface methodology (RSM) was used to optimize microencapsulation yield
      (MY) using three independent variables; the ratio of coating material to core
      material (w/w, X1), the emulsifier concentration (%, v/v, X2), and the CaCl2
      concentration (%, w/v, X3). In the preparation of sodium alginate (SA)
      microcapsule, the regression model equation for the MY was predicted as follows;
      MY(%) = 56.02 + 3.64X2 + 3.18X1X2 - 3.74X2(2). The optimal conditions for the SA
      microcapsule were obtained at the [SA]/[alpha-TP] ratio of 6.6:3.4 (w/w),
      [emulsifier] of 1.35% (v/v), and [CaCl2] of 4.3% (w/v), and the predicted MY in
      this condition was of 57.2%. In vitro alpha-TP releasing test of the SA-based
      microcapsules was performed. The SA microcapsule released 28.8% of alpha-TP when
      exposed in the simulated gastric fluid (SGF, pH 1.2) for 24 h. In the simulated
      intestinal fluid (SIF, pH 7.4), the amount of released alpha-TP (81.5%) was
      significantly greater than that in the SGF. The duration time required for
      releasing 50 (T50%) and 70% (T70%) of alpha-TP from the SA-microcapsule were
      calculated to be 3.8 and 12.3 h, respectively. From these results, it was
      suggested that SA microcapsule would be structurally resistant against acidic
      environment, and it would rapidly release core material under mild alkali
      condition.

PMID- 16417916
TI  - A retrospective clinical study on longevity of posterior composite and amalgam
      restorations.
AB  - OBJECTIVES: The purpose of this study was to evaluate retrospectively the
      longevity of class I and II amalgam and composite resin restorations placed in a
      general practice. METHODS: Patient records of a general practice were used for
      collecting the data for this study. From the files longevity and reasons for
      failure of 2867 class I and II amalgam and composite resin restorations placed in
      621 patients by two operators between 1990 and 1997 were recorded in 2002.
      RESULTS: 912 amalgam restorations (502 by operator 1 and 410 by operator 2) and
      1955 posterior composite resin restorations (1470 by operator 1 and 485 by
      operator 2) were placed. One hundred and eighty-two amalgam and 259 posterior
      composite resin restorations failed during the observation period. The main
      reasons for failure of the restorations were caries (34%), endodontic treatment
      (12%) and fracture of the tooth (13%). Life tables calculated from the data
      reveal a survival for composite resin of 91.7% at 5 years and 82.2% at 10 years.
      For amalgam the survival is 89.6% at 5 years and 79.2% at 10 years. Cox
      regression analysis resulted in a significant effect of the amount of restored
      surfaces on the survival of the restorations. No significant effect of operator,
      material as well as combination of material and operator was found. SIGNIFICANCE:
      In the investigated general practice, two dentists obtained comparable longevity
      for amalgam and composite resin restorations.

PMID- 16417918
TI  - Comparative analysis of refolding of chemically denatured beta-lactoglobulin
      types A and B using the dilution additive mode.
AB  - The kinetic refolding of beta-lactoglobulin (BLG), types A and B, by beta
      cyclodextrin, glucose and sorbitol has been investigated in aqueous solution
      using fluorescence, far UV-CD and UV-spectrophotometric techniques. A new Pd
      complex has been used to denature the protein. CD and fluorescence studies
      indicated that when incubated with sugar, the denatured BLG is refolded into the
      native-like structure through the dilution additive mode resulting in a higher
      yield of active protein than without sugar. CD studies show that these sugars can
      induce a non-native alpha-helical structure in denatured BLG-A and -B, then aid
      in the refolding of the protein. Based on the present study, these sugars have a
      different effect on BLG-A than BLG-B because of their differences in protein
      thermal stability. BLG-A has a higher thermal stability than BLG-B due to
      differences in the amino acid sequences.

PMID- 16417920
TI  - Myelodysplastic syndrome with transformation to acute monocytic leukemia with
      FLT3-ITD mutation following orthotopic liver transplantation.
AB  - A rare case of a 46-year-old man who underwent myelodysplastic syndrome, acute
      monocytic leukemia with FLT3-ITD mutation and splenic disruption following
      orthotopic liver transplantation is reported. The study of this case may be
      helpful to understand both the pathogenesis of acute leukemia and new
      complication of liver transplantation.

PMID- 16417919
TI  - Immunophenotypic characterization of IgVH3-72 B-cell chronic lymphocytic
      leukaemia (B-CLL).
AB  - The frequent expression of the otherwise rare IgVH3-72 gene was demonstrated in
      highly stable B-cell chronic lymphocytic leukaemias (B-CLLs). Here we describe
      the immunophenotypic profiles of eleven IgVH3-72 B-CLLs, by investigating
      expression of ZAP-70 and of a set of surface antigens previously demonstrated to
      represent the signature of distinct B-CLL prognostic groups. All IgVH3-72 B-CLLs
      revealed a homogeneous immunophenotypic profile, expressing all the markers
      associated with good prognosis, but not those representing the signature of bad
      prognosis B-CLLs, including ZAP-70. Our results corroborate the notion that IgVH3
      72 B-CLLs represent a molecularly and immunophenotypically homogeneous disease
      group with a good prognosis.

PMID- 16417921
TI  - Expression of small hairpin RNAs for S100A9 used in the protein function
      research.
AB  - To study the function of S100A9 protein in HL-60 cells treated with all-trans
      retinoic acid (ATRA), we had designed and constructed retroviral vectors for
      expression of small hairpin RNAs (shRNAs), and silenced S100A9 expression in HL
      60 cells treated with ATRA. The silence efficiency of siRNA was detected with RT
      PCR and Western blotting. The differentiation of HL-60 was monitored by nitro
      blue tetrazolium (NBT) reduction experiment. Western blot showed that shRNAs
      remarkably reduce of S100A9 expression in HL-60 cells when they were induced to
      differentiation by ATRA. But NBT positive percentage of differentiated HL-60
      cells was no remarked change with S100A9 expression. The data indicated S100A9
      could be no important action during differentiation of HL-60 treated with ATRA.

PMID- 16417923
TI  - Quantitative analysis of thermotaxis in the nematode Caenorhabditis elegans.
AB  - Thermotaxis (TTX) is one of the sophisticated behaviors in the nematode
      Caenorhabditis elegans. Although the mechanisms of thermotaxis have been deduced
      from different studies, they are controversial. Previous studies proposed a
      behavioral model where thermotaxis is regulated by the counterbalance between two
      opposite driving forces, while recent studies proposed stochastic models. In this
      study, we analyzed thermotaxis by a novel quantitative population TTX assay using
      a gentle linear thermal gradient. Analysis of thermotaxis in wild type animals
      revealed a clear thermal preference to a cultivation temperature with regard to
      the distribution of animals and the TTX mean expressing temperature preference. A
      time course assay revealed that the behavioral response to a preferred
      temperature was initially suppressed for at least 15 min in the animals
      cultivated at 23 degrees C, but not in those cultivated at 17 degrees C. Our
      result provides a possible explanation for the inconsistency between the various
      studies on thermotaxis and is consistent with the early behavioral model, where
      thermotaxis is regulated by the counterbalance between two driving forces.

PMID- 16417922
TI  - Evaluation of CD7 and terminal deoxynucleotidyl transferase (TdT) expression in
      CD34+ myeloblasts from patients with myelodysplastic syndrome.
AB  - There is an emerging use of flow cytometry to evaluate patients with
      myelodysplastic syndrome (MDS). We have studied CD7 and TdT expression in the
      CD34+ myeloid blast cell population in 55 bone marrow samples of patients with
      MDS. CD7 and/or TdT were detected in 38 out of 55 patients (69%). CD7 expression
      was not related to other bad prognosis data but conversely, we found an
      association between TdT+ CD34 myeloblasts and high-risk MDS patients according to
      the International Prognostic Scoring System. Therefore, CD7 and TdT may help to
      establish the diagnosis of MDS and, TdT expression also seems to be a useful
      marker in distinguishing risk groups.

PMID- 16417924
TI  - Individually dosed oral drug administration to socially-living transponder-tagged
      mice by a water dispenser under RFID control.
AB  - The sensitivity of behavioral and physiological parameters to even mildly
      stressful experiences such as drug injections creates a need for alternative
      methods. We have established a method of stress-free administration of drugs via
      drinking water that allows multiple, individually specific and exact dosages,
      even for socially-housed animals. The drug solution is supplied by a dispenser
      with automated volume control. Animals are PIT microchip-tagged with RFID
      transponders and identified in realtime at the water port. Computer control
      permits preprogramming of individual reward quantities so that drug
      administration is terminated after an individual has collected its daily dose.
      For our experiments, the substance 5-bromo-2'-deoxyuridine (BrdU) was given as a
      marker of proliferating cells that we quantified in the hippocampus of adult
      mice. Experimental groups received BrdU either via intraperitoneal injections or
      orally via the water dispensers. Immunohistochemical staining of BrdU-positive
      cells was of the same quality after oral administration as after injection. BrdU
      positive cells did not differ statistically in cell numbers. Thus, water
      dispensers under transponder control allow the individual and stress-free
      application of drugs even to group-living animals without disturbing their
      behavior. This is useful where a complex temporal protocol of application is
      required, and for phenotyping experiments combining behavioral tests with neural,
      cellular or molecular analyses.

PMID- 16417925
TI  - An improved method for long-term measuring of hemolymph fluctuations of non
      essential amino acids, GABA and histamine from freely moving crayfish.
AB  - The microdialysis method was adapted to obtain long-term hemolymph dialysates
      from the pericardial cavity of freely moving Procambarus clarkii crayfish, to
      measure fluctuations of non-essential amino acids, GABA and histamine by high
      performance liquid chromatography using off-line fluorometric derivatization.
      Asp, Ala, Tau, GABA and histamine (HA) reached its maximal concentrations at the
      daybreak, whereas glutamate (Glu), Gln and Gly peaked at the end of the light
      period. The minimum and maximal detected amounts for each substance along the 24h
      cycle were (in microM): 20-300Asp, 100-200Glu, 400-700Gln, 400-600Gly, 100
      200Tau, 150-300Ala, 2-10 GABA and 25-250HA. Cocktails containing the relative
      concentration of each amino acid, GABA and histamine resulted in a
      hyperpolarization that reduced the spontaneous firing of cultured peptidergic X
      organ neurons. Glu, GABA and histamine evoked a long-lasting hyperpolarization
      that suppressed the spontaneous firing, whereas Asp, Gly and Tau evoked a
      depolarization accompanied with neuronal firing. Finally, neither Ala nor Gln
      modified the resting membrane potential.

PMID- 16417926
TI  - Auditory neuropathy/auditory dys-synchrony detected by universal newborn hearing
      screening.
AB  - The implementation of neonatal hearing screening has enabled early detection and
      intervention in hearing loss. The use of otoacoustic emissions (OAE) and auditory
      brainstem response testing in universal screening has led to the recognition of
      this recently described disorder called auditory neuropathy/auditory dys
      synchrony (AN/AD). This diagnosis indicates that the infant has significant
      hearing loss despite having normal outer hair cells in the cochlea. We reviewed
      the characteristics and natural history of nine infants detected to have AN/AD
      from universal newborn hearing screening in a national pediatric hospital. Fifty
      two cases of hearing loss were detected from 14,807 consecutively screened cases.
      Of the 52 cases, 9 had electrophysiological test results consistent with AN/AD.
      They include both premature infants who had major neonatal complications and term
      infants with no perinatal complications. Six cases had bilateral and three cases
      had unilateral findings. We suggest that AN/AD can occur in low-risk infants and
      hence screening of high-risk cases alone is insufficient. Our findings are
      discussed with reference to the current literature.

PMID- 16417927
TI  - Laboratory diagnosis of contagious ecthyma: comparison of different PCR protocols
      with virus isolation in cell culture.
AB  - A new polymerase chain reaction (PCR) assay for rapid diagnosis of contagious
      ecthyma was designed and applied to 21 clinical samples from Greece. This assay,
      which detects a highly conserved gene from the parapox genome, was evaluated for
      its sensitivity and specificity in order to be considered as a useful diagnostic
      tool. A comparative study with two published PCR protocols one using primers PPP1
      PPP3, PPP1-PPP4 which targets putative virion envelope gene B2L and the other
      using VIR1-VIR2 primers which amplifies ORF virus interferon resistant (VIR)
      gene, as well as cell culture virus neutralization assay was carried out. All
      samples tested were amplified successfully with the PCR protocol established in
      the laboratory. The combination of primers PPP1-PPP3 and PPP1-PPP4 in a semi
      nested PCR gave a positive result in 20 of 21 samples while primers VIR1-VIR2
      failed to amplify successfully 7 of 21 samples. The diagnostic value of parapox
      viral DNA amplification was also compared with the results of virus isolation by
      cell culture and was positive in three samples that the virus isolation was
      obtained.

PMID- 16417928
TI  - Failure to genotype Human Cytomegalovirus by PCR-RFLP method due to sequence
      variation within the primer binding site.
AB  - Polymerase chain reaction-based restriction fragment length polymorphism (PCR
      RFLP) is one of the rapid methods for genotyping Human Cytomegalovirus (HCMV).
      When genotyping clinical samples by a sensitive nested PCR-based RFLP method for
      the glycoprotein B (gB) gene of HCMV, it was found that some of the clinical
      specimens did not give an amplification signal. Analysis of the prototype
      sequences of the different genotypes showed base pair mismatches over the primer
      binding site. An alternative assay is suggested for genotyping of HCMV.

PMID- 16417929
TI  - Confirmation of electron microscopy results by direct testing of viruses adhered
      to grids using nucleic acid amplification techniques.
AB  - It is possible to visualize rapidly viral particles by electron microscopy (EM)
      in patient samples and in cell cultures, and characterize the particles on the
      basis of their size and morphology. In many instances, EM has contributed to the
      diagnosis of specific infectious agents. Four different types of viruses with
      different characteristics of particle size, capsid structure, the presence or
      absence of an envelope, genomic content and stability outside the host were
      screened and diagnosed by EM at the level of family/genus. The results were
      confirmed at the species level by elution of the sample material from the grids
      used for EM examination and nucleic acid amplification. This approach could be
      valuable in situations where the immediate diagnosis is unclear, or when new
      infectious agents appear.

PMID- 16417930
TI  - An immunocytometric assay based on dengue infection via DC-SIGN permits rapid
      measurement of anti-dengue neutralizing antibodies.
AB  - Dengue remains a global public health threat and development of a safe and
      effective vaccine is a principal public health goal. The primary correlate of
      immunity is thought to be neutralizing antibodies. Currently, the plaque
      reduction neutralization test (PRNT) is the gold standard measure of dengue
      neutralizing antibody responses, but this test is limited by time-consuming
      performance. In addition, some feel that use of viral strains adapted to grow in
      Vero or BHK cells may not accurately reflect protective responses. A human cell
      line transfected to express a putative natural dengue receptor, DC-SIGN (CD209),
      was used to measure antibody-mediated dengue neutralization. Using neutralizing
      monoclonal antibodies, immune sera, and laboratory adapted dengue viruses,
      serotype-specific neutralizing activity was demonstrated similar to that seen in
      the Vero PRNT. Importantly, serotype-specific neutralizing activity against
      recently isolated dengue strains with less heterotypic cross-neutralization than
      laboratory adapted viruses was also demonstrated.

PMID- 16417931
TI  - Resolving repeatedly borderline results of Hybrid Capture 2 HPV DNA Test using
      polymerase chain reaction and genotyping.
AB  - The Hybrid Capture 2 HPV DNA Test (hc2) (Digene Corporation, Gaithersburg, MD) is
      at present the only FDA approved assay for routine detection of human
      papillomavirus (HPV) infections. A significant analytical inaccuracy of the hc2
      near to cut-off was reported recently. To address this problem, 240 samples with
      repeatedly borderline/equivocal/indeterminate hc2 results (samples with repeated
      RLU/CO values between 0.4 and 4.0) were tested using the PGMY09/PGMY11 consensus
      PCR and genotyping in order to resolve their high-risk HPV status. All
      PGMY09/PGMY11 PCR negative samples were tested in addition using CPI/IIg
      consensus PCR. A false negative rate of 11.3% and false positive rate of 19.1%
      were recorded in the samples with repeatedly borderline hc2 results. The
      corresponding hc2 false reactivity rates in 95 samples selected at random which
      were clearly hc2 negative (samples with RLU/CO values less than 0.4) and 124
      samples selected at random which were clearly hc2 positive (samples with RLU/CO
      values more than 4.0) were 4.2% and 5.6%, respectively. The proportion of hc2
      false reactivity increased with proximity to the hc2 cut-off value. According to
      the results of the present study, the introduction of an hc2 grey-zone and
      retesting of samples with repeatedly borderline hc2 results by an alternate HPV
      detection method, such as the PGMY09/PGMY11 consensus PCR and genotyping, is
      recommended.

PMID- 16417932
TI  - A reverse transcription-nested PCR assay for HHV-6 mRNA early transcript
      detection after transplantation.
AB  - Monitoring of human herpesvirus-6 (HHV-6) reactivation is important, especially
      in immunocompromised patients such as transplant recipients. Reverse
      transcription PCR (RT-PCR) is a useful method to distinguish between latent and
      active infection. Here, a RT-nested PCR coupled with a colorimetric plate
      hybridization assay was established to detect HHV-6 types A and B U79/80 mRNAs.
      After confirming the reliability of the assay on HHV-6 cultures, it was applied
      to the detection of HHV-6 reactivation after renal (27 patients), bone marrow (14
      patients) or heart (7 patients) transplantation. A total of 206 blood samples
      were tested from renal (137), bone marrow (58) and heart (11) transplant
      recipients. U79/80 mRNAs were found in 32 samples that were considered as
      indicative of HHV-6 reactivation: 15, 13 and 5 from kidney, bone marrow and heart
      transplant recipients, respectively. Finally, U79/80 mRNA detection was
      correlated with clinical manifestations including leucopenia, skin rash, graft
      rejection or dysfunction and diarrhoea.

PMID- 16417933
TI  - C-reactive protein initiates transformation of Leishmania donovani and L.
      mexicana through binding to lipophosphoglycan.

PMID- 16417934
TI  - Evaluation of an iscom ELISA used for detection of antibodies to Neospora caninum
      in bulk milk.
AB  - The intracellular parasite Neospora caninum is increasingly recognized as an
      important cause of abortion and stillbirth in cattle. Presence of specific
      antibodies indicates infection, and the immunostimulating complex (iscom) enzyme
      linked immunoassay (ELISA) has previously been evaluated for use on individual
      milk and sera. In the present study, this test is investigated for use on bulk
      milk. In this study, 124 herds were used to analyse the relationship between
      within-herd prevalences based on individual sera and bulk milk optical densities.
      The individual test results were translated into a herd-level result, which
      enabled comparison of the bulk milk test result to the aggregate of individual
      serum results. The relative contribution of milk from cows with different milk
      yield and antibody status to the tank, i.e. its composition, was expected to
      influence the outcome of the bulk milk test. Therefore, sensitivity and
      specificity were calculated at different cut-off levels, not only using a
      standard cross-tabulation technique, but also a logistic regression model. By
      using the latter method, the sensitivity and specificity could be estimated
      adjusting for milk yield covariates. Specificity was estimated to be high (
      approximately 98%) at the 0.20 cut-off, which can be used as a decision threshold
      to rule in infection. With more equal emphasis on sensitivity and specificity, a
      lower cut-off should be used. Although infection cannot be completely ruled out,
      herds with test results below 0.05 are highly likely to be non-infected. The
      within-herd prevalence of false negative herds is probably less than 10-15% at
      this level. From what is known about test performance at the individual level and
      the prevalence of infection, the estimate of the specificity of the bulk milk
      test should be quite accurate while the sensitivity is likely to be
      underestimated. We confirmed that the performance of the bulk milk test depends
      on the milk tank composition. In particular the milk yield of cows with high
      antibody levels affects the probability of a positive outcome of the bulk milk
      test.

PMID- 16417935
TI  - Confirmation of the expression of a large set of conserved hypothetical proteins
      in Shewanella oneidensis MR-1.
AB  - High-throughput "omic" technologies have allowed for a relatively rapid, yet
      comprehensive analysis of the global expression patterns within an organism in
      response to perturbations. In the current study, 9503 different tryptic peptides
      were identified with high confidence from capillary liquid chromatography-mass
      spectrometry analysis of 26 chemostat cultures of Shewanella oneidensis MR-1
      under various conditions. Using at least one distinctive and a total of two total
      peptide identifications per protein, we detected the expression of 758 conserved
      hypothetical proteins. This included 359 such proteins previously described
      [Kolker, E., Picone, A.F., Galperin, M.Y., Romine, M.F., Higdon, R., Makarova,
      K.S., Kolker, N., Anderson, G.A., Qiu, X., Auberry, K.J., Babnigg, G., Beliaev,
      A.S., Edlefsen, P., Elias, D.A., Gorby, Y.A., Holzman, T., Klappenbach, J.A.,
      Konstantinidis, K.T., Land, M.L., Lipton, M.S., McCue, L.A., Monroe, M., Pasa
      Tolic, L., Pinchuk, G., Purvine, S., Serres, M.H., Tsapin, S., Zakrajsek, B.A.,
      Zhu, W., Zhou, J., Larimer, F.W., Lawrence, C.E., Riley, M., Collart, F.R.,
      Yates, J.R., III, Smith, R.D., Giometti, C.S., Nealson, K.H., Fredrickson, J.K.,
      Tiedje, J.M., 2005. Global profiling of Shewanella oneidensis MR-1: expression of
      hypothetical genes and improved functional annotations. Proc Natl Acad Sci U S A
      102, 2099-2104] with an additional 399 reported herein for the first time. The
      latter 399 proteins ranged from 5.3 to 208.3 kDa, with 44 being of 100 amino acid
      residues or less. Using a combination of information including peptide detection
      in cells grown under specific culture conditions and predictive algorithms such
      as PSORT and PSORT-B, possible/plausible functions are proposed for some
      conserved hypothetical proteins. Such proteins were found not only to be
      expressed, but 19 were only expressed under certain culturing conditions, thereby
      providing insight into potential functions. These findings also impact the
      genomic annotation for S. oneidensis MR-1 by confirming that these genes code for
      expressed proteins. Our results indicate that 399 proteins can now be upgraded
      from "conserved hypothetical protein" to "expressed protein in Shewanella," 19 of
      which appeared to be expressed under specific culture conditions.

PMID- 16417936
TI  - Disruption of Escherichia coli, Listeria monocytogenes and Lactobacillus sakei
      cellular membranes by plant oil aromatics.
AB  - The role of membrane disruption in the bactericidal activity of the plant oil
      aromatic compounds eugenol, carvacrol and cinnamaldehyde was investigated using
      confocal laser scanning microscopy, changes in ATP levels and cell viability. In
      25 mM HEPES buffer pH 7 at 20 degrees C, 10 mM eugenol or carvacrol increased
      uptake of propidium iodide by Escherichia coli, Listeria monocytogenes and
      Lactobacillus sakei over a 10-min period. The same treatments resulted in lowered
      viability, rapid depletion of cellular ATP and release of ATP, with the exception
      of Lb. sakei treated with carvacrol. Eugenol or carvacrol at 5 mM to 10 mM
      inhibited E. coli and L. monocytogenes motility. Lb. sakei was resistant to
      cinnamaldehyde. Thus, its effects were only studied on E. coli and L.
      monocytogenes. At 10 mM, cinnamaldehyde caused a slight but statistically
      significant increase in propidium iodide staining of E. coli, but had no effect
      on L. monocytogenes. Cinnamaldehyde treatment of E. coli at 10 mM and L.
      monocytogenes at 40 mM resulted in decreased cellular ATP, but there was no
      concomitant release of ATP. Cinnamaldehyde at 5 and 10 mM inhibited E. coli and
      L. monocytogenes motility. Results for eugenol and carvacrol are consistent with
      non-specific permeabilization of the cytoplasmic membrane. Evidence for increased
      membrane permeability by cinnamaldehyde is less conclusive. The release of ATP
      from eugenol and carvacrol-treated cells and absence of release from
      cinnamaldehyde-treated cells could indicate that eugenol and carvacrol possess
      ATPase inhibiting activity. Secondary effects would also be consistent with
      membrane disruption.

PMID- 16417937
TI  - An endornavirus from a hypovirulent strain of the violet root rot fungus,
      Helicobasidium mompa.
AB  - We determined the complete nucleotide (nt) sequence (16,614 nt) of a large double
      stranded (ds) RNA (referred to as L1 dsRNA), previously identified as the
      hypovirulence factor from strain V670 of the violet root rot fungus,
      Helicobasidium mompa. The positive-strand of L1 dsRNA contained a long open
      reading frame (ORF) potentially encoding a protein of 5,373 amino acids
      (molecular mass 603,080 Da) with conserved motifs characteristic of RNA-dependent
      RNA polymerase (RdRp) and helicase. The ORF is the longest so far reported in the
      fungal kingdom. The putative RdRp and helicase were shown to be related to
      putative RdRps and helicases of members of the genus Endornavirus. As is the case
      with endornaviruses, the coding (sense) strand of L1 dsRNA contained a
      discontinuity (nick) at nt position 2,552. A region between the RdRp and helicase
      domains of the polyprotein also had an amino acid sequence, resembling UDP
      glycosyltransferases (UGTs) in Oryza sativa endornavirus and Phytophthora
      endornavirus 1. Regions in the L1 dsRNA-encoded protein presumed to contain
      putative helicase, UGT and RdRp motifs were present at comparable positions to
      those in other endornaviruses. L1 dsRNA of H. mompa strain V670 was assigned to
      the genus Endornavirus, and here, we designate it as H. mompa endornavirus 1-670
      (HmEV1-670). This represents the first report of a fungal endornavirus whose
      complete nucleotide sequence has been determined.

PMID- 16417939
TI  - The why's of Y-based motifs in alphaherpesvirus envelope proteins.
AB  - The Alphaherpesvirinae are large DNA viruses and represent the largest subfamily
      of the Herpesviridae with closely related members of man and animal, including
      herpes simplex virus, varicella-zoster virus, pseudorabies virus, bovine
      herpesvirus 1, and many others. The viral envelope proteins of alphaherpesviruses
      are remarkably diverse and are incorporated in the ER, Golgi, and plasma membrane
      of infected cells. The cytoplasmic domain of many of these envelope proteins
      contain specific tyrosine-based amino acids. During recent years, accumulating
      evidence indicates that these tyrosine-based motifs serve different important
      functions during the virus life cycle, and are implicated in endocytosis
      processes, intracellular trafficking, basolateral and axonal sorting, and signal
      transduction events. The current minireview will discuss the functions associated
      with these tyrosine-based motifs in alphaherpesvirus envelope proteins.

PMID- 16417938
TI  - Prevalence of antiretroviral drug resistance mutations and HIV-1 non-B subtypes
      in newly diagnosed drug-naive patients in Slovenia, 2000-2004.
AB  - In order to estimate the prevalence and patterns of antiretroviral drug
      resistance mutations in drug-naive HIV-1 infected patients in Slovenia, and the
      prevalence of non-B subtypes, a retrospective study was conducted on a cohort,
      representing 87% of the total of newly diagnosed HIV-1 infected patients, in a 5
      year period (2000-2004). Protease (PR) and reverse transcriptase (RT) sequences
      were determined in 77 newly diagnosed HIV-1 patients. Non-B subtypes were present
      in 18% of the population tested. Transmitted drug resistance was identified as in
      the CATCH study: the presence of primary PR and RT gene mutations according to
      the IAS-USA mutation list including the revertant mutations in codon 215 and
      excluding mutations on the RT positions 44 and 118. The estimated prevalence of
      transmitted resistance mutations was 3.9%. Namely, three out of 77 patients had
      mutations associated with resistance to NRTIs: one patient carried M184V in
      association with A62V, while a revertant mutation T215D was found in two
      patients. No transmitted drug resistance to NNRTIs or PIs was detected. However,
      to score the expected response to therapy using the REGA and the Stanford
      algorithms, we also took into account secondary PR mutations and additional RT
      mutations. Reduced response to some therapeutic options was predicted in five
      patients (6.5%). In conclusion, testing the vast majority of all newly diagnosed
      HIV-1 patients in the last 5 years in Slovenia uncovered a relatively high
      prevalence of non-B subtypes and a low prevalence of transmitted drug resistance.

PMID- 16417941
TI  - Exploring the relationships between diabetes and smoking: with the development of
      glucose equivalent concept for diabetes management.
AB  - The extent of interaction between smoking and diabetes has been under
      appreciated. Smokers had more diabetes, and when diabetes patients smoke, the
      combined mortality effect was greater than either the addition or multiplication
      of these two medical problems. Patients seen in the office are usually more
      interested in reducing blood glucose than in quitting smoking, and yet, smoking
      caused mortality risks, at a magnitude similar to or more than diabetes. The
      concept of "glucose equivalent of smoking" was developed to direct more attention
      to smoking in clinical management. Based on the follow-up observations from a
      large Asian cohort, the risk of an individual who smokes, from all-cause
      mortality, was found to be equivalent to an elevation of blood glucose by an
      average of 41mg/dl for the cohort in general and 68mg/dl for the diabetes in
      particular. By relating the message of smoking hazards in terms of "glucose
      equivalent", clinicians will be more alerted to counsel and patients will be more
      likely to quit. Appreciating this concept has a potential to change the paradigm
      of diabetes management, to bridge the clinical disconnect between the two, and to
      provide new ammunition for the diabetes epidemic in Taiwan.

PMID- 16417940
TI  - A modified viral satellite DNA-based gene silencing vector is effective in
      association with heterologous begomoviruses.
AB  - We have previously reported effective gene silencing of a transgene and
      endogenous plant genes in tobacco and tomato plants using a modified viral
      satellite DNA associated with Tomato yellow leaf curl China virus (TYLCCNV). In
      this study, we constructed a similar gene silencing vector (DNADeltaC12beta)
      based on the satellite DNAbeta associated with Tobacco curly shoot virus (TbCSV)
      by replacing its betaC1 gene with a multiple cloning site. Strong and stable
      silencing of cognate genes was achieved when this vector, carrying a fragment of
      the green fluorescent protein (GFP) transgene or a sulfur (Su) endogenous gene
      encoding one unit of the chloroplast enzyme magnesium chelatase required for
      chlorophyll II production, was co-agroinoculated with TbCSV used as a helper
      virus. GFP silenced transgenic Nicotiana benthamiana plants appear red under UV
      illumination due to loss of green fluorescence, while the Su silenced plants
      appear white as a result of failure to synthesize chlorophyll. Our results show
      that the efficiency of Su silencing is independent of the insert orientation in
      both N. benthamiana and N. glutinosa plants. Most significant however, is the
      observation that in association with heterologous begomoviruses, such as TYLCCNV
      or Malvastrum yellow vein virus, the DNADeltaC12beta vector could still
      effectively induce transgene and endogenous gene silencing in tobacco plants.
      These observations suggest that the modified viral satellite DNA vector can be
      applied as a reverse genetics tool for the study, analysis and discovery of gene
      function in more plants.

PMID- 16417942
TI  - Oral magnesium administration prevents thermal hyperalgesia induced by diabetes
      in rats.
AB  - BACKGROUND: Peripheral neuropathy is a common complication of diabetes mellitus.
      It has been shown that hyperglycemia may contribute to its development but the
      exact pathophysiology underlying this complication is not fully understood. Since
      oral magnesium supplementation can normalize hyperglycemia induced by diabetes in
      rats, this study was designed to examine the effect of oral magnesium
      administration on thermal hyperalgesia in streptozocin-induced diabetic rats.
      MATERIAL AND METHODS: Twenty-four male adult wistar rats were divided equally
      into control, magnesium-treated control, diabetic and magnesium-treated diabetic
      groups. In magnesium-treated diabetic rats, magnesium sulfate (10g/l) was added
      into the drinking water once diabetes was established (10 days after STZ
      injection) and continued for 8 weeks. Mg-treated control animals received
      magnesium sulfate in the same dose and over the same time period. The other two
      groups; control and diabetic animals, only received tap water. At the end of the
      8 weeks, thermal pain threshold was assessed by tail flick test and magnesium and
      glucose plasma levels were measured in all groups. RESULT: A significant decrease
      (p<0.001) in thermal pain threshold and plasma magnesium levels and an increase
      in plasma glucose levels (p<0.001) were seen in diabetic rats 8 weeks after
      diabetes induction. After 8 weeks of oral magnesium, thermal hyperalgesia was
      normalized and plasma magnesium and glucose levels were restored towards normal.
      CONCLUSION: It is concluded that oral magnesium administration given at the time
      of diabetes induction may be able to restore thermal hyperalgesia, magnesium
      deficiency and hyperglycemia and in diabetic rats.

PMID- 16417943
TI  - Impact of diabetes on health-related quality of life in a population study in
      Japan.
AB  - Diabetes may impact on health-related quality of life (HRQOL). The aim of this
      population-based study was to confirm this influence. We examined 2135 residents
      aged > or =30 years in an entire community, who had no history of cancer or
      cardiovascular disease and did not require care for daily activity. The response
      rate was 87.8%. The status of diabetes, other chronic diseases and life practices
      were assessed by self-reported questionnaires, in which HRQOL was evaluated by
      the Japanese version SF-36, based on five sub-scales of the domain. Diabetes had
      been diagnosed in 165 (7.7%) of the study population. Comparison of data,
      adjusted for sex, age, living alone and employment status between non-diabetics
      and subjects with diabetes treated by pharmacological therapy had odds ratios
      (ORs) between the lowest quartiles of sub-scale scores of 1.90 for physical role,
      2.51 for general health, and 1.79 for emotional role. The OR for lower general
      health was also increased in people using only lifestyle modification for
      treatment of diabetes. Although the OR for mental health was worse in the
      lifestyle modification group it was not increased in people with diabetes on
      pharmacological therapy. These associations remained almost unchanged after
      adjustment for the covariates. The sub-scales of physical and emotional roles and
      general health were decreased significantly in diabetics with duration of disease
      between 10 and 19 years or > or =20 years. Our study showed treatment of diabetes
      clearly influenced HRQOL, with this influence being dependent on the duration of
      diabetes and primarily affecting physical rather than mental health.

PMID- 16417944
TI  - Comment on "Survival improvement in resectable non-small cell lung cancer with
      (neo)adjuvant chemotherapy: results of a meta-analysis of the literature" by T.
      Berghmans, M. Paesmans, A.P. Meert, C. Mascaux, P. Lothaire, J.J. Lafitte, et al.
      [Lung Cancer 49 (2005) 13-23.].

PMID- 16417945
TI  - Inotropic and lusitropic effects of ghrelin and their modulation by the
      endocardial endothelium, NO, prostaglandins, GHS-R1a and KCa channels.
AB  - Contractile effects of ghrelin (10(-9) to 10(-6) M) were tested in rat papillary
      muscles of normal (n = 50) and hypertrophic (n = 16) right ventricles (RV). RV
      hypertrophy was induced by pulmonary hypertension using monocrotaline. In normal
      muscles, ghrelin was added either alone (n = 9) or after pre-treatment with
      indomethacin (cycloxygenase inhibitor, 10(-5) M; n = 10), L-nitro-L-arginin (NO
      synthase inhibitor, 10(-4) M; n = 9), D-Lys(3)-GHRP-6 (GHS-R1a antagonist; 10(-4)
      M; n = 8) or apamin+charybdotoxin (KCa channels blockers; 10(-6) M, n =7 ), as
      well as after damaging the endocardial endothelium (n = 7). In hypertrophic
      muscles, ghrelin was added either alone (n = 9) or after pre-treatment with
      apamin+charybdotoxin (10(-6 M, n=7). Ghrelin concentration-dependently decreased
      active tension (AT) and maximal velocity of tension rise (negative inotropic
      effect), as well as, maximal velocity of tension decay (negative lusitropic
      effect) and time to AT (onset of relaxation). These effects were maximal at 10(
      6) M, similar in normal and hypertrophic muscles and were significantly altered
      only by apamin+charybdotoxin, indomethacin and L-nitro-L-arginin.
      Apamin+charybdotoxin attenuated the negative inotropic effect, while indomethacin
      and L-nitro-L-arginin, respectively, blunted and exacerbated the premature onset
      of relaxation. In conclusion, ghrelin induces negative inotropic and lusitropic
      effects and an earlier onset of relaxation in normal and hypertrophic myocardium,
      which are independent of GHS-R1a, since they were not affected by D-Lys(3)-GHRP
      6. The negative inotropic effect is partly mediated by KCa channels, while the
      earlier onset of relaxation is modulated by prostaglandins and NO.

PMID- 16417946
TI  - PKC-dependent stimulation of EAAT3 glutamate transporter does not require the
      integrity of actin cytoskeleton.
AB  - The activity and the membrane expression of EAAT3 glutamate transporter are
      stimulated upon PKC activation by phorbol esters in C6 rat glioma cells. To
      investigate the role of cytoskeleton in these effects, we have employed actin
      perturbing toxins and found that the perturbation of actin cytoskeleton inhibits
      basal but not phorbol-stimulated EAAT3 activity and membrane trafficking. In the
      absence of phorbols, latrunculin A, a toxin that disassembles actin cytoskeleton,
      produced a rapid inhibition of EAAT3 activity, due to a decrease in transport
      V(max). The inhibitory effect was fully reversible and was not detected for other
      sodium dependent transport systems for amino acids. However, latrunculin did not
      prevent the increase in transport caused by phorbol esters and, moreover, cells
      pre-treated with phorbols were resistant to the inhibitory effect of the toxin on
      EAAT3 activity. Biotinylation experiments indicated that the inhibitory effect of
      latrunculin was attributable to a decreased expression of the carrier on the
      membrane, while the toxin did not suppress the PKC-dependent increase in EAAT3
      membrane abundance. Latrunculin A effects on EAAT3 were shared by cytochalasin D,
      a toxin that disorganizes actin filaments with a distinct mechanism of action. On
      the contrary, a small, but significant, increase of EAAT3 activity was observed
      upon incubation with jasplakinolide, a drug that stabilizes actin microfilaments.
      Also jasplakinolide, however, did not hinder phorbol-dependent stimulation of
      aspartate transport. Colchicine, a toxin that disrupts microtubules, also lowered
      EAAT3 activity without preventing transport stimulation by phorbols, while
      microtubule stabilization by paclitaxel led to an increase in aspartate
      transport. It is concluded that, in C6 cells, the PKC-mediated stimulatory
      effects on EAAT3 are cytoskeleton-independent, while in the absence of phorbols,
      the transporter is partially inhibited by the disorganization of either actin
      microfilaments or microtubules. These results suggest that EAAT3 trafficking in
      C6 cells involves different pools of transporters.

PMID- 16417947
TI  - Increase in apoptosis with neural differentiation and shortening of the lifespan
      of P19 cells overexpressing tau.
AB  - Apoptosis or programmed cell death is considered to be involved in
      neurodegenerative disorders including Alzheimer's disease (AD). AD is
      characterized by intracellular aggregates of hyperphosphorylated tau, a
      microtubule-associated protein. To investigate the effect of the overexpression
      of tau in P19 cells, we engineered P19 wild-type cells (P19wt) stably expressing
      human tau441 (P19tau). When P19tau cells were induced to undergo neural
      differentiation by treatment with retinoic acid (RA), a remarkable increase in
      apoptosis was observed. However, in the undifferentiated state, there was no
      notable difference of phenotype between P19wt and P19tau cells. Additionally, we
      found that tau dissociated from microtubules, and co-localized with the RA
      receptor (RAR) at nucleoli. Further, the lifespan of the differentiated P19tau
      cells was shorter than that of P19wt cells, and the re-treatment of
      differentiated P19wt cells with RA resulted in a reduction of lifespan. These
      observations suggested that tau affects RA signaling in apoptosis and lifespan
      during the neural differentiation induced by RA treatment.

PMID- 16417948
TI  - In vitro mutagenicity of anti-inflammatory parsalmide analogues PA7, PA10, and
      PA31 triggered by biotransformation into hydroxy derivatives.
AB  - In this study, the mutagenicity of the anti-inflammatory parsalmide [5-amino-N
      butyl-2-(2-propynyloxy)-benzamide] analogues PA7 [5-amino-N-butyl-2-cyclohexyloxy
      benzamide], PA10 [5-amino-N-butyl-2-phenoxy-benzamide] and PA31 [5-amino-N-butyl
      2-(p-tolyloxy)-benzamide] was determined by an Ames Salmonella assay. The
      experiments were performed by preincubating the compounds in the absence and
      presence of a post-mitochondrial fraction (S9) of rat liver homogenate from
      phenobarbital/beta-naphtoflavone treated rats. No mutagenic effect was observed
      after direct testing (no S9 added) in Salmonella typhymurium strains TA98, TA100,
      TA102, TA1535 and TA1537. However, in the presence of S9, the test substances
      triggered mutagenic responses in strains TA100 and TA98. PA31 presented the
      strongest mutagenic potential. The reversion rates in the presence of PA31 were
      about 2-19 fold higher than spontaneous mutation rates. In the presence of PA7,
      the reversion increased 2-14-fold over spontaneous rates. While PA10 showed a
      relatively mild mutagenic potential, as the number of revertants did not exceed
      2.5 times the number of spontaneous mutations. Mass spectrometric analysis of the
      in vitro biotransformation showed that S9 converted (%), regioselectively, PA7
      (19%), PA10 (7%) and PA31 (12%) into hydroxy-derivatives.

PMID- 16417949
TI  - Mycobacterial 70 kD heat-shock protein is an effective subunit vaccine against
      bovine paratuberculosis.
AB  - Paratuberculosis is a chronic granulomatous inflammation of the small intestine
      of cattle and other ruminants, caused by infection with Mycobacterium avium ssp.
      paratuberculosis (MAP). The disease can be found in ruminant herds worldwide,
      causing substantial economic losses at farm level due to premature culling and
      production losses. In previous studies, it has been shown that immune responses
      to recombinant MAP Hsp70 proteins were predominantly cell mediated. As protective
      immunity to the intracellular mycobacterial pathogens is thought to be cell
      mediated in origin, we have studied the use of a recombinant MAP Hsp70 as a
      subunit vaccine in cattle experimentally infected with MAP. The results of the
      current study demonstrate that recombinant MAP Hsp70 can be successfully used as
      a subunit vaccine against bovine paratuberculosis, significantly reducing
      shedding of bacteria in feces during the first 2 years following experimental
      infection.

PMID- 16417950
TI  - Duration of protection of rabbits after vaccination with Bacillus anthracis
      recombinant protective antigen vaccine.
AB  - Long-term protection of rabbits that had been vaccinated with two doses of a
      recombinant protective antigen (rPA) vaccine was examined against an aerosol
      spore challenge with the Ames isolate of Bacillus anthracis at 6 and 12 months.
      At 6 months after the primary injection, survival was 74.1% (20/27) with
      quantitative ELISA titer of 22.3 microg of anti-rPA IgG per millilitre and toxin
      neutralizing antibody (TNA) assay titer of 332. At 12 months after the primary
      injection, only 37.5% (9/24) of the rabbits were protected with quantitative
      ELISA titer of 19.8 microg of anti-rPA IgG per millilitre and TNA assay titer of
      286. There was a significant loss of protection (p = 0.0117) and a significant
      difference in survival curves (p = 0.0157) between the 6- and 12-month groups.
      When ELISA or TNA assay titer, gender, and challenge dose were entered into a
      forward logistic regression model, week 26 ELISA titer (p = 0.0236) and week 13
      TNA assay titer (p = 0.0147) for the 6-month group, and week 26 ELISA titer (p =
      0.0326) and week 8 TNA assay titer (p = 0.0190) for the 12-month group, were
      significant predictors of survival. Neither gender nor challenge dose were
      identified as having a statistically significant effect on survival. Booster
      vaccinations with rPA may be required for the long-term protection of rabbits
      against anthrax.

PMID- 16417951
TI  - Effectiveness of abbreviated and delayed 7-valent pneumococcal conjugate vaccine
      dosing regimens.
AB  - We estimated the effectiveness of abbreviated regimens of 7-valent pneumococcal
      conjugate vaccine (PCV7) based on serotyped cases of invasive pneumococcal
      disease (IPD) in children under 5 reported from 2001 to 2004 to two US
      surveillance programs. Vaccination regimens included in the analysis were 1 dose
      < 3 months old, 2 doses < 5 months old, 3 doses < 7 months old, full schedule (3
      doses and a booster), 1 dose at 12-23 months, and 2 doses at 12-23 months.
      Vaccine effectiveness (VE) was calculated as (1-Mantel-Haenszel summary odds
      ratio in vaccinated children, as compared to unvaccinated children)x100% for each
      regimen, stratifying by year. Among 400 eligible cases, for vaccine-type IPD, VE
      was 90.5% for the full schedule, 76.6% for 3 doses < 7 months old, and 70.5% for
      2 doses < 5 months old; 1 dose < 3 months provided no significant protection. No
      regimen provided significant protection against vaccine-related serotypes. Data
      for regimens begun at 12-23 months were inconclusive. These data support the use
      of the 2-dose and 3-dose infant PCV7 regimens when the full series cannot be
      delivered and detail the limitations of abbreviated dosing regimens.

PMID- 16417952
TI  - Antibody responses to meningococcal (groups A, C, Y and W135) polysaccharide
      diphtheria toxoid conjugate vaccine in children who previously received
      meningococcal C conjugate vaccine.
AB  - A randomised, modified, double-blind trial was conducted in children 2 to < 5
      years of age to evaluate immunogenicity and reactogenicity of a meningococcal
      (serogroups A, C, Y, W135) diphtheria toxoid conjugate vaccine (MCV-4) in healthy
      children previously vaccinated with a monovalent meningococcal C conjugate
      vaccine. Participants received one dose of either MCV-4 or Haemophilus influenzae
      type b vaccine (Hib vaccine, control group). Serum bactericidal antibodies (SBA)
      were determined in sera obtained before and approximately 28 days following
      vaccination. MCV-4 was highly immunogenic for serogroups A, C, Y and W135, the
      response to serogroup C being consistent with a booster response in participants
      primed with monovalent C conjugate vaccine. No major between-group differences in
      solicited local and systemic reactions or adverse events (AEs).

PMID- 16417953
TI  - Rapid, high-level production of hepatitis B core antigen in plant leaf and its
      immunogenicity in mice.
AB  - Hepatitis B core antigen (HBc or HBcAg) self-assembles into capsid particles and
      is extremely immunogenic. HBc has been extensively studied for its production in
      various expression systems and for the use of HBc particles for high-density,
      immunogenic presentation of foreign epitopes. Here we reported the high-level
      transient expression of HBc in plant leaf and its immunogenicity in mice. By
      using a novel plant viral expression system, HBc was produced in Nicotiana
      benthamiana leaves at levels up to 7.14% of total soluble protein (TSP) or 2.38
      milligrams HBc per gram of fresh weight at 7 days post-infection (dpi). Plant
      derived HBc (p-HBc) assembled into virus-like particles (VLPs) as revealed by
      sucrose gradients and electron microscopy. Partially purified p-HBc stimulated
      strong serum antibody responses in mice as Escherichia coli-derived HBc upon
      intraperitoneal (i.p.) injection. Furthermore, mice immunized mucosally (orally
      and intranasally) with p-HBc in the absence of adjuvants also developed HBc
      specific serum IgG as well as intestinal IgA. Taken together, our results
      indicate the potential usefulness of p-HBc-VLP as a carrier for immunogenic
      presentation and mucosal delivery of foreign epitopes.

PMID- 16417954
TI  - A modified HIV challenge assay in mice by using luciferase-expressing vaccinia
      virus.
AB  - In this study, we developed a simple and sensitive assay in mice for a challenge
      experiment by using a recombinant vaccinia virus dual-expressing antigen (HIV Env
      gp160) and firefly luciferase. This assay can detect the vaccine effect at real
      time in vivo by using a small amount of mouse serum. The luciferase activity in
      mouse serum was in agreement with the viral titer in the ovary. This assay would
      be applicable as a challenge model for infectious diseases.

PMID- 16417955
TI  - Retrospective assessment of influenza vaccine effectiveness among the non
      institutionalized elderly population in Japan.
AB  - To construct a framework for monitoring the effectiveness of influenza vaccine,
      we retrospectively surveyed elderly (> or = 65 years old) people living in rural
      areas of Kyoto prefecture, Japan, using a self-administered questionnaire, for
      their influenza-related symptoms during the peak influenza season of 2003-2004. A
      total of 2301 elderly individuals responded, of whom 1533 (66.6%) had been
      vaccinated. The odds ratio (OR) of vaccination for fever of > or = 38 degrees C,
      adjusted for sex, age and underlying conditions, was 0.77 (95% confidence
      interval (CI), 0.40-1.47), and the OR for a diagnosis of influenza in clinics was
      0.81 (95% CI, 0.41-1.57). These findings suggested that the vaccine was 20%
      effective, although this effectiveness was not statistically significant.

PMID- 16417956
TI  - Sculpting the immunological response to dengue fever by polytopic vaccination.
AB  - The twin challenges of immunodominance and heterologous immunity have hampered
      discovery of an effective vaccine against all four dengue viruses. Here, we
      explore how the T cell competition and selection underlying these asymmetrical
      properties impede effective T cell vaccine design. The theory we develop predicts
      dengue vaccine clinical trial data well. From the insights that we gain by this
      theory, we propose two new ideas for design of epitope-based T cell vaccines
      against dengue: polytopic injection and subdominant epitope priming.

PMID- 16417957
TI  - Vaccination with the divergent portion of the protein histone H2B of Leishmania
      protects susceptible BALB/c mice against a virulent challenge with Leishmania
      major.
AB  - To identify approaches for vaccination against leishmaniasis, we analyzed the
      protective effect of different constructions using recombinant peptides from the
      protein Leishmania (L.) major histone H2B. H2B sequence displays two distinct
      regions: an amino-terminal region divergent from mammalian H2B (27% identity) and
      a carboxy-terminal region highly conserved with mammalian H2B (55% identity). We
      tested the ability of the entire H2B protein, its divergent or conserved regions
      to provide protection against virulent L. major challenge. While the recombinant
      H2B protein adjuved with CpG induces potent cellular and antibody responses when
      injected to BALB/c mice, only the divergent amino-terminal region of H2B is able
      to confer potent protection against a virulent challenge. These findings indicate
      that different portions of the same parasite protein may express contrasting
      protective effects likely through the induction of different effector mechanisms.
      Due to its potent protective properties in the BALB/c mouse model, the amino
      terminal region of Leishmania H2B could constitute a good vaccine candidate.

PMID- 16417958
TI  - On "No definitive evidence for L-Zagreb mumps strain associated aseptic
      meningitis: a review with special reference to the da Cunha study", Vaccine
      2005;23:5286-8, by Kulkarni PS, et al.

PMID- 16417959
TI  - A two-compartment exposure device for foliar uptake study.
AB  - An airtight two-chamber exposure devise was designed for investigating foliar
      uptake of polycyclic aromatic hydrocarbons (PAHs) by plants. The upper and the
      bottom chambers of the device were air-tightly separated by an aluminum foil and
      the plant aerial tissues and roots were exposed in the two chambers,
      respectively. The device was tested using maize exposed to several PAH species.
      Positive correlations between air and aerial tissue concentrations of the exposed
      PAH species were revealed. PAHs spiking in the culture solution had no influence
      on the leaf concentrations.

PMID- 16417960
TI  - Obesity does not adversely affect results in patients who are undergoing in vitro
      fertilization and embryo transfer.
AB  - OBJECTIVE: To examine the outcome of in vitro fertilization according to the body
      mass index of infertile patients. STUDY DESIGN: Between September 2003 and May
      2005, 573 patients underwent 789 in vitro fertilization cycles or ICSI because of
      male factor, tubal factor, and unexplained infertility were retrospectively
      included from our IVF database. The patients were classified in four groups:
      BMI<20 kg/m2 (264 cycles), 20< or = BMI<25 (394 cycles), 25< or = BMI < 30 (83
      cycles), and BMI> or = 30 (48 cycles). All patients had a long protocol for IVF
      with a combination of the GnRH agonist and recombinant FSH. RESULTS: All
      parameters of ovarian response were comparable except the total required r-FSH
      dose. This dose was statistically higher in the group of BMI> or = 30 compared to
      the other groups (p = 0.0003). All parameters of IVF outcome were comparable,
      including the cancellation rate, the implantation rate, and pregnancy rates.
      CONCLUSION: Obese patients require a higher r-FSH dose to achieve follicular
      maturation than normal weight patients. Obesity does not affect negatively
      results of in vitro fertilization.

PMID- 16417961
TI  - Substaging pathologically organ confined (pT2) prostate cancer: an exercise in
      futility?

PMID- 16417962
TI  - Diffusion and economic consequences of health technologies in prostate cancer
      care in Sweden, 1991-2002.
AB  - OBJECTIVE: To describe the diffusion of six main health technologies used for
      management of prostate cancer, to estimate the economic consequences of
      technological changes, and to explore factors behind the diffusion. METHODS: Data
      describing the diffusion 1991-2002 were obtained from population-based databases.
      Costs were obtained from Linkoping University Hospital and Apoteket AB. Factors
      affecting the diffusion of the technologies were explored. RESULTS: Utilization
      of technologies with a curative and/or palliative aim has increased over time,
      except for surgical castration. PSA-tests are used increasingly. The total cost
      of the study technologies has increased from 20 million euros in 1991 to 65
      million euros in 2002. Classification of radical prostatectomy revealed a profile
      associated with a slow/limited diffusion, while classification of PSA-tests
      revealed a profile associated with a rapid/extensive diffusion. CONCLUSIONS:
      Several technological changes in the management of prostate cancer have occurred
      without proven benefits and have contributed to increased costs. There are other
      factors, besides scientific evidence, that have an impact on the diffusion.
      Consequently, activities aimed at facilitating an appropriate diffusion of new
      technologies are needed. The analytical framework used here may be helpful in
      identifying technologies that are likely to experience inappropriate diffusion
      and therefore need particular attention.

PMID- 16417963
TI  - Prostatic infarction involving the urinary sphincter, an association with
      pyoderma gangrenosum.
AB  - A 70-year-old man presented with haematuria and restrictive urinary symptoms 7
      years after a transurethral prostatectomy (TURP). Onset of symptoms coincided
      with development of a large skin ulcer on his back. A diagnosis of pyoderma
      gangrenosum was made based on clinical signs and histopathology. On repeated
      cystoscopy the urethral sphincter was obliterated by necrotic tissue, suspicious
      for malignancy. Histopathology revealed only necrotic tissue consistent with
      infarction of the prostate and sphincter. This clinical presentation with
      infarction of the prostate and sphincter, concurrent with development of skin
      ulcers, was consistent with pyoderma gangrenosum affecting the prostatic
      urothelium and sphincter. Previous prostatic surgery may have predisposed our
      patient to development of pyoderma gangrenosum in the area of the prostate.

PMID- 16417964
TI  - Botulinum A toxin intravesical injections in the treatment of painful bladder
      syndrome: a pilot study.
AB  - OBJECTIVE: We evaluated the efficacy and tolerability of botulinum A toxin (BTX
      A) intravesical injections in patients affected by painful bladder syndrome with
      increased urinary frequency, refractory to conventional treatment modalities.
      METHODS: Twelve women and two men were prospectively included in the study. Under
      short general anaesthesia patients were given injections of 200 U of commercially
      available BTX-A diluted in 20 ml 0.9% NaCl. Injections were performed
      submucosally in the trigone and bladder floor under cystoscopic control. Voiding
      chart, the Visual Analog Scale (VAS) for pain, and urodynamics were performed
      before treatment and 1 and 3 mo afterward. RESULTS: Overall, 12 patients (85.7%)
      reported subjective improvement at 1 and 3 mo follow-up. The mean VAS score was
      significantly reduced at 1 and 3 mo after treatment (p<0.05 for both); at the
      same time points daytime and nighttime urinary frequency significantly decreased
      (p<0.01 and p<0.05, respectively), and bladder cystometric capacity significantly
      increased (p<0.01). Two patients reported incomplete bladder emptying. We did not
      detect any systemic side effects during or after treatment. CONCLUSIONS: The
      results of this pilot study indicate that BTX-A intravesical injections are
      effective in the short-term management of painful bladder syndrome. By modulating
      afferent C-fiber activity within the bladder walls, BTX-A significantly improves
      urodynamic parameters and reduces bladder pain and urinary frequency.

PMID- 16417965
TI  - Identification of novel gamete receptors that mediate sperm adhesion to the egg
      coat.
AB  - Mammalian fertilization is initiated by the species-specific binding of sperm to
      the zona pellucida, or egg coat. Earlier studies suggested that sperm-egg
      adhesion in mouse is mediated by the binding of beta1,4-galactosyltransferase-I
      (GalT) on the sperm surface to specific glycoside ligands on the egg coat
      glycoprotein, ZP3. Binding of multiple ZP3 oligosaccharides induces GalT
      aggregation, triggering a pertussis toxin-sensitive G-protein cascade leading to
      induction of the acrosome reaction. Consistent with this, sperm bearing targeted
      deletions in GalT are unable to bind ZP3 nor undergo ZP3-dependent acrosomal
      exocytosis; however, GalT-null sperm are still able to bind to the egg coat. This
      indicates that sperm-egg binding requires at least two independent binding
      mechanisms: a GalT-ZP3-independent event that mediates initial adhesion, followed
      by a GalT-ZP3 interaction that facilitates acrosomal exocytosis. During the past
      few years, novel GalT-ZP3-independent gamete receptors have been identified that
      appear to participate in initial gamete adhesion. On such receptor is SED1, an
      EGF repeat and discoidin domain protein that coats sperm as they traverse through
      the epididymis, and which is required for sperm to bind the egg coat. Similarly,
      a novel egg coat ligand is present on ovulated oocytes, but not on ovarian eggs,
      and which also appears to function in initial sperm binding. The identification
      of novel gamete receptors that are required for sperm-egg binding opens up new
      avenues for the development of specific contraceptive strategies.

PMID- 16417966
TI  - Aldo-keto reductase (AKR) 1C3: role in prostate disease and the development of
      specific inhibitors.
AB  - Human aldo-keto reductases (AKR) of the 1A, 1B, 1C and 1D subfamilies are
      involved in the pre-receptor regulation of nuclear (steroid hormone and orphan)
      receptors by regulating the local concentrations of their lipophilic ligands.
      AKR1C3 is one of the most interesting isoforms. It was cloned from human prostate
      and the recombinant protein was found to function as a 3-, 17- and 20-ketosteroid
      reductase with a preference for the conversion of Delta4-androstene-3,17-dione to
      testosterone implicating this enzyme in the local production of active androgens
      within the prostate. Using a validated isoform specific real-time RT-PCR
      procedure the AKR1C3 transcript was shown to be more abundant in primary cultures
      of epithelial cells than stromal cells, and its expression in stromal cells
      increased with benign and malignant disease. Using a validated isoform specific
      monoclonal Ab, AKR1C3 protein expression was also detected in prostate epithelial
      cells by immunoblot analysis. Immunohistochemical staining of prostate tissue
      showed that AKR1C3 was expressed in adenocarcinoma and surprisingly high
      expression was observed in the endothelial cells. These cells are a rich source
      of prostaglandin G/H synthase 2 (COX-2) and vasoactive prostaglandins (PG) and
      thus the ability of recombinant AKR1C enzymes to act as PGF synthases was
      compared. AKR1C3 had the highest catalytic efficiency (kcat/Km) for the 11
      ketoreduction of PGD2 to yield 9alpha,11beta-PGF2 raising the prospect that
      AKR1C3 may govern ligand access to peroxisome proliferator activated receptor
      (PPARgamma). Activation of PPARgamma is often a pro-apoptotic signal and/or leads
      to terminal differentiation, while 9alpha,11beta-PGF2 is a pro-proliferative
      signal. AKR1C3 is potently inhibited by non-steroidal anti-inflammatory drugs
      suggesting that the cancer chemopreventive properties of these agents may be
      mediated either by inhibition of AKR1C3 or COX. To discriminate between these
      effects we developed potent AKR1C inhibitors based on N-phenylanthranilic acids
      that do not inhibit COX-1 or COX-2. These compounds can now be used to determine
      the role of AKR1C3 in producing two proliferative signals in the prostate namely
      testosterone and 9alpha,11beta-PGF2.

PMID- 16417967
TI  - Manganese induces inducible nitric oxide synthase (iNOS) expression via
      activation of both MAP kinase and PI3K/Akt pathways in BV2 microglial cells.
AB  - It is well documented that manganese neurotoxicity induces clinical symptoms
      similar to those of idiopathic Parkinson's disease. Although microglial cytotoxic
      mediator-induced neurotoxicity is suggested, the mechanism by which manganese up
      regulates cytotoxic mediator, such as nitric oxide (NO), remains poorly
      understood. Therefore, in this study, we investigated the mechanism of manganese
      on induction of iNOS in microglial cells. iNOS promoter/luciferase assay revealed
      that manganese (500 (M) regulated the iNOS expression at the transcriptional
      level. Immunoblot analysis also revealed that phosphorylation levels of ERK, JNK
      MAPKs and Akt (PKB, PI 3-kinase downstream effector), were increased. Both
      protein and mRNA levels of iNOS expression were abrogated by specific inhibitors,
      SP600125 (JNK inhibitor, 20 microM), PD98059 (ERKs inhibitor, 50 microM), or
      LY294002 (PI 3-kinase inhibitor, 20 microM), but not by SB203580 (20 microM), a
      p38 specific inhibitor. These data lead to the conclusion that manganese
      regulates the iNOS expression at the transcriptional level in BV2 microglial
      cells and the increased iNOS protein expression is mediated via both JNK-ERK MAPK
      and PI3K/Akt signaling pathways, but not via p38 MAPK pathway. Increased iNOS
      protein level was also found in RAW264.7 murine macrophage cells.

PMID- 16417969
TI  - Do any insects other than phlebotomine sandflies (Diptera: Psychodidae) transmit
      Leishmania infantum (Kinetoplastida: Trypanosomatidae) from dog to dog?

PMID- 16417968
TI  - Molecular diagnosis of anthelmintic resistance.
AB  - Conventional and real time polymerase chain reaction-based tests have been
      developed for the diagnosis of anthelmintic resistance (AR) in populations of
      several small and large ruminant as well as horse gastro-intestinal nematode
      species. To date, molecular markers that correlate well with AR are available
      only for the detection of benzimidazole resistance. Recently, however, a single
      nucleotide polymorphism was found in vitro to be of functional relevance for
      reduced drug efficacy to macrocylic lactones. The focus of the present review,
      therefore, is the molecular mechanism of action of these two drug classes and
      potential applications of this knowledge to the diagnosis of AR. It is argued
      that a prerequisite for future molecular diagnosis will be tests providing
      reliable and exact quantification of resistance related alleles in DNA extracted
      from representative pools of parasites.

PMID- 16417970
TI  - Development and evaluation of a PCR assay for the detection of Cytauxzoon felis
      DNA in feline blood samples.
AB  - Cytauxzoonosis is an emerging tick borne infectious disease of domestic cats in
      the United States, caused by the organism Cytauxzoon felis (C. felis). In
      naturally infected domestic cats the disease is almost always fatal. Currently
      there are no commercially available molecular or serologic tests to facilitate
      the antemortem diagnosis of C. felis infection. Clinical and pathological
      diagnosis of cytauxzoonosis is based on microscopic identification of parasites
      in tissues or on blood smears. We have developed and evaluated the sensitivity
      and specificity of a polymerase chain reaction (PCR) based assay for the
      diagnosis of C. felis infections in feline blood samples. The assay is sensitive
      enough to detect one copy of a cloned fragment of the C. felis 18S rRNA gene.
      This PCR assay can be used for the rapid clinical diagnosis of cytauxzoonosis and
      for epidemiological studies that will better define the geographic distribution
      of C. felis infection in cats.

PMID- 16417971
TI  - A 2.9 kDa Fasciola hepatica-recombinant protein based ELISA test for the
      detection of current-ovine fasciolosis trickle infected.
AB  - The suitability of an enzyme linked immunosorbent assay (ELISA) test with a 2.9
      kDa Fasciola hepatica-recombinant protein (FhrAPS) for diagnosing early and
      current-ovine fasciolosis was analyzed, and compared to that obtained by using a
      direct ELISA for detecting F. hepatica-circulating FhES antigens and to the
      coprological sedimentation for fluke egg quantitation. Fourteen Gallega
      autochthonous breed sheep were experimentally infected with metacercariae by a
      trickle system (small repetitive infections) and divided into two groups: G-I
      represented a primary infection for 34 weeks; G-R, animals with primary infection
      and reinfected 18 w.a.p.i. Seven sheep were left uninfected as the control group
      (G-C). Serum IgG antibody values against the FhrAPS rose rapidly by 1st w.a.p.i.
      in all infected sheep. Antibody levels in those with primary infection (G-I, G-C)
      peaked at 10 weeks, diminishing slightly and levelling from 16 to 34 weeks. Those
      with primary infection reinfected at 18 weeks had a rebound effect with the
      highest values observed. Circulating F. hepatica-ES antigens were detected by the
      1st w.a.p.i. in all infected groups peaking at 6 weeks, decreasing rapidly to
      uninfected control values by 10 weeks of infection. Faecal egg-output started 11
      weeks after primary infection. An increase in the IgG antibody as well as antigen
      responses to the FhrAPS and to anti-FhES from the 18 w.a.p.i. was recorded in G-T
      and G-R after the challenge infection. Antibody levels remained high whereas
      antigenemia values diminished after 6 weeks. A positive significant correlation
      between the IgG response against the FhrAPS and the F. hepatica circulating
      antigens (r2 = 0.428, p = 0.001) was obtained. In conclusion, our standardized
      diagnostic ELISA for fasciolosis based on the detection of IgG responses to the
      FhrAPS would be a valuable tool to diagnosis early and current F. hepatica
      infections in sheep.

PMID- 16417972
TI  - Supranational comparison of Neospora caninum seroprevalences in cattle in
      Germany, The Netherlands, Spain and Sweden.
AB  - Herd, within-herd and animal prevalences for Neospora caninum in beef and dairy
      cattle were compared between four countries. In randomly selected herds from
      regions of Germany, The Netherlands, Spain and Sweden that were representative
      for the cattle production of these countries, all animals > or = 2 years were
      examined serologically by enzyme-linked immunosorbent assays (ELISAs) with high
      test specificity (> 98.0%). In a previous study, the ELISAs had been validated
      against each other. Single reacting animals within a herd were confirmed by
      immunobloting. At the time of sampling, animal (age, breed, herdtype, sex,
      lactation stage) and herd data (region) were collected. Considerable differences
      in N. caninum herd, within-herd, and overall animal prevalence estimations were
      observed between countries, regions, herdtype, age categories and breeds. Herd
      prevalences, based on confirmation of single reactors, for dairy herds were
      estimated to be 16% (95%CI: 10-24%) in Sweden, 49% (95%CI: 39-59%) in Germany,
      63% (95%CI: 57-69%) in Spain and 76% (95%CI: 67-84%) in The Netherlands and for
      beef herds 41% (95%CI: 31-50%) in Germany, 46% (95%CI: 41-51%) in Spain and 61%
      (95%CI: 50-72%) in The Netherlands. No beef herds were examined in Sweden. The
      lowest animal true prevalence was estimated in dairy cattle in Sweden (0.5%
      (95%CI: 0.1-0.8%)) while the highest animal true prevalence was estimated for
      dairy cattle in Spain (16.2% (95%CI: 14.9-17.5%)). Within-herd prevalences varied
      greatly, with very few farms in Sweden having more than 10% seropositive animals
      while in Spain more than 10% of the herds had within-herd prevalences between 50
      and 100%. Seropositivity was significantly associated with herdtype (beef versus
      dairy), age, breed and region within countries. The results of this supranational
      comparative study showed that the importance of N. caninum infection varied
      greatly within in Europe. Estimates of prevalence can be used to calculate the
      economic impact of N. caninum infection as well as to evaluate the effect of
      prevention and control strategies over time.

PMID- 16417973
TI  - Ring-Toss: Capping highly exposed tyrosyl or tryptophyl residues in proteins with
      beta-cyclodextrin.
AB  - We have used UV difference spectroscopy and fluorescence spectroscopy to study
      the perturbation by beta-cyclodextrin of tyrosyl or tryptophyl residues located
      at each of the 10 variable consensus contact positions in the third domain of
      turkey ovomucoid. The goal was to monitor the accessibility of the side chain
      rings of these residues when located at these positions. The results indicated
      that the tyrosyl or tryptophyl rings are most highly exposed when located in the
      P1 position followed by the P4 position. It was possible to determine the
      association constants for beta-cyclodextrin binding at these positions. When
      located at the P2, P5, P6 and P3' positions, the rings of the tyrosyl or
      tryptophyl residues were exposed but less so than at the P1 or P4 positions. By
      contrast, when located at the P1', P2', P14' and P18' positions, the tyrosyl or
      tryptophyl residues were insufficiently exposed to be perturbed by beta
      cyclodextrin, although they reacted positively to dimethyl sulfoxide solvent
      perturbation. These findings indicate that beta-cyclodextrin perturbation
      provides a convenient way to detect highly exposed tyrosyls or tryptophyls in
      proteins. Furthermore, we evaluated the ability of beta-cyclodextrin to inhibit
      the interaction of turkey ovomucoid third domain variants with different P1
      residues. The results showed that the presence of beta-cyclodextrin had little
      effect on the association constant when the P1 residue was a glycyl residue, but
      greatly decreased the association constant when the P1 residue was a tyrosyl or
      tryptophyl residue. Thus, beta-cyclodextrin may be used to selectively modulate
      the interaction between proteinase inhibitors and their cognate enzymes.

PMID- 16417974
TI  - Working memory for order and the parietal cortex: an event-related functional
      magnetic resonance imaging study.
AB  - Memory for order information has been tied to the frontal lobes, however,
      parietal activation is observed in many functional neuroimaging studies. Here we
      report functional magnetic resonance findings from an event-related experiment
      involving working memory for order. Five letters were presented for storage,
      followed after a delay by two probe items. Probe items could be separated by zero
      to three positions in the memory set and subjects had to indicate whether the
      items were in the correct order. Analyses indicate that activation in left
      parietal cortex shows a systematic decrease in activation with increasing probe
      distance. This finding is consistent with an earlier study in which we suggested
      that parietal cortical regions mediate the representation of order information
      via magnitude codes.

PMID- 16417975
TI  - mu-Opioid receptor internalization-dependent and -independent mechanisms of the
      development of tolerance to mu-opioid receptor agonists: Comparison between
      etorphine and morphine.
AB  - A growing body of evidences suggests that receptor desensitization is implicated
      in the development of tolerance to opioids, which is generally regulated by
      protein kinases and receptor trafficking proteins. In the present study, we
      demonstrated that repeated s.c. treatment with etorphine, but not morphine,
      produced a significant increase in protein levels of G protein-coupled receptor
      kinase 2, dynamin II, beta-arrestin 2 and phosphorylated-conventional protein
      kinase C in membranes of the mouse spinal cord, suggesting that the etorphine
      induced mu-opioid receptor desensitization may result from G protein-coupled
      receptor kinase 2/dynaminII/beta-arrestin2-dependent phosphorylation of mu-opioid
      receptors. Unlike etorphine, morphine failed to change the levels of these
      trafficking proteins. Furthermore, we found that the level of glial fibrillary
      acidic protein in the mouse spinal cord was clearly increased by chronic in vivo
      and in vitro treatment with morphine, whereas no such effect was noted by
      etorphine. In the behavioral study, intraperitoneal pretreatment with the glial
      modulating agent propentofylline suppressed the development of tolerance to
      morphine-induced antinociception. In addition, intrathecal injection of
      astrocytes and astrocyte-conditioned medium mixture, which were obtained from
      cultured astrocytes of the newborn mouse spinal cord, aggravated the development
      of tolerance to morphine. In contrast, these agents failed to affect the
      development of tolerance induced by etorphine. These findings provide direct
      evidence for the distinct mechanisms between etorphine and morphine on the
      development of tolerance to spinal antinociception. These findings raise the
      possibility that the increased astroglia response produced by chronic morphine
      could be associated with the lack of mu-opioid receptor internalization.

PMID- 16417977
TI  - Predictors of engagement in continuing care following residential substance use
      disorder treatment.
AB  - BACKGROUND: Patients in intensive SUD programs who subsequently participate in
      continuing care for a longer interval have better outcomes than those who
      participate for a shorter interval. We sought to identify patient and program
      factors associated with duration of engagement in SUD continuing care after
      residential/inpatient treatment. METHODS: Patients (n=3032) at 15 geographically
      diverse SUD residential treatment programs provided data on demographics, symptom
      patterns, recovery resources, and perceptions of treatment environment. We
      identified patient characteristics associated with the number of consecutive
      months of engagement in continuing care. We then consolidated and classified risk
      factors into an integrated model. RESULTS: Being African American, having more
      SUD and psychiatric symptoms, more resources for recovery, and perceiving the
      treatment staff as being supportive were associated with longer engagement in
      continuing care. African Americans' engagement in continuing care was 17% longer
      than Caucasians'. The positive effect of being African American was partially
      mediated by having taken actions toward changing use, and by the presence of
      psychotic symptoms. CONCLUSION: These results extend previous research on the
      predictors of continuing care engagement after residential SUD programs.
      Clinicians can use information about characteristics that put patients at risk
      for shorter engagement in continuing care to target patients who might benefit
      from interventions to increase engagement in continuing care.

PMID- 16417978
TI  - Suitability of canine herpesvirus as a vector for oral bait vaccination of foxes.
AB  - Studies were conducted to evaluate the feasibility of using canine herpesvirus
      (CHV) as a vaccine vector for bait-delivered oral vaccination of wild foxes. To
      test the viability of CHV in baits, CHV was freeze-dried, incorporated into
      different baits, stored, and the remaining viral infectivity tested in cell
      culture after varying periods of time at different storage temperatures.
      Experimental baits (mouse carcasses) and commercial baits (FOXOFF and PROBAIT)
      were prepared with either liquid or freeze-dried CHV and tested in two fox trials
      for their capacity to induce CHV-specific antibodies following oral baiting.
      Freeze-drying and storage temperatures below 0 degrees C had a stabilizing effect
      to virus infectivity. When stored at -20 degrees C, freeze-dried CHV retained its
      full infectivity for up to 3 months in PROBAIT baits, the remaining infectivity
      in FOXOFF baits was 100-fold less. Oral baiting with CHV induced antiviral serum
      antibodies in all vaccinated foxes (20/20). None of the vaccinated foxes became
      ill or shed infectious virus into the environment although viral DNA was detected
      in body secretions as evaluated by PCR. The results indicate that CHV can be
      freeze-dried and stored over extended periods of time without loosing much of its
      infectivity. This is the first report of CHV being used for oral bait vaccination
      of foxes. It appears that CHV is well suited for use as a recombinant vector for
      wild canids.

PMID- 16417979
TI  - Pharmacologically active natural products in the defence secretion of Palembus
      ocularis (Tenebrionidae, Coleoptera).
AB  - The tenebrioid beetle Palembus ocularis Casey 1891 has been used in the
      traditional medicine of Central and South America to treat Asthma bronchiale.
      Palembus ocularis has large pygidial glands filled with defence chemicals. The
      defence fluid was analysed by GLC and GLC-MS. The main components are quinones,
      such as hydroquinone, 2-ethylhydroquinone as major and 2-methylhydroquinone as
      minor metabolite. Furthermore, terpenes, fatty acids and their esters,
      cholesterol and lactones were discovered, with 1-pentadecene as a major
      component. Pharmacological experiments were carried out with the defence fluid
      and isolated compounds in order to find out if a rational base exists for the use
      in traditional medicine. 5-Lipoxygenase is inhibited by crude extracts and
      hydroquinone. Moreover, a combination of different hydroquinones was 20-times
      more effective than individual substances suggesting a synergistic effect. The
      inhibitory effect could be further increased with addition of 1-pentadecene. Anti
      inflammatory activity was determined by HET-CAM. The polar extracts of Palembus
      ocularis showed anti-inflammatory activity in this system. Pure hydroquinone
      exhibited a similar activity as crude extracts indicating that it constitutes the
      active principle. The 5-LOX and HET-CAM-assays provide good evidence that
      hydroquinones in the defence fluid of Palembus ocularis have anti-inflammatory
      properties which would explain the traditional use of this beetle to treat
      asthma.

PMID- 16417980
TI  - Evaluation of the mutagenic and antimutagenic effects of South African plants.
AB  - Dichloromethane and 90% methanol extracts of 42 South African plants were
      screened for mutagenicity and antimutagenicity using the Salmonella/microsome
      mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial
      strains in the presence and absence of metabolic activator S9. The methanol
      extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and
      Helichrysum rugulosum indicated mutagenicity. These are the first reported tests
      on the mutagenicity of Helichrysum species. Six species indicated antimutagenic
      properties, all in the presence of S9: methanol leaf extract of Bauhinia
      galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum
      myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and
      Sutherlandia frutescens.

PMID- 16417981
TI  - Hypolipidemic effects of acute and sub-chronic administration of an aqueous
      extract of Ajuga iva L. whole plant in normal and diabetic rats.
AB  - Diabetes is often accompanied by lipid abnormalities, which contribute
      significantly to cardiovascular (CV) morbidity and mortality in diabetic
      patients. The plant Ajuga iva (L.) Schreiber (Labiatea) is used in the treatment
      of diabetes in Moroccan folk medicine. Previously, we have demonstrated potent
      hypoglycemic activity and relatively non-toxic nature of a lyophilized aqueous
      extract of the whole plant (AI-extract) in normal (normoglycemic) and
      streptozotocin (STZ)-diabetic rats. In this study, we examined the AI-extract for
      its possible lipid-lowering activity in normal and STZ-diabetic rats. Taurine
      (TR) and glibenclamide (GLB) were used as reference substances. As shown
      previously, the AI-extract (10 mg/kg; oral) reduced plasma glucose levels after
      acute (single) and sub-chronic (3 weeks) dosing both in normal and diabetic rats.
      In normal rats, single and repeated oral administration of the AI-extract, at a
      dose of 10 mg/kg produced a small but significant decrease in plasma CHL levels
      (P<0.05). A single dose of the AI-extract did not produce a significant change in
      plasma TG, but sub-chronic dosing (for up to 21 days) caused a significant
      decrease in plasma TG (P<0.05). In STZ-diabetic rats, a single dose as well as
      repeated (3 weeks) treatment with the AI-extract produced a significant decrease
      in plasma CHL (P<0.01), and triglyceride (P<0.01) levels. The AI-extract also
      prevented weight loss in the diabetic animals. In summary, an aqueous extract of
      the Ajuga iva whole plant showed hypolipidemic activity, in addition to its
      hypoglycemic effect in normoglycemic and diabetic rats. In view of the
      hypoglycemic and hypolipidemic activity, and its relatively non-toxic nature
      (shown previously), Ajuga iva may be a candidate for development as an anti
      diabetic agent in humans. Further studies are warranted to confirm our results
      and fractionate the AI-extract to isolate and identify the active principle(s),
      and to determine the exact mechanism(s) of action.

PMID- 16417982
TI  - Retrofacial approach of cochlear implantation in inner ear malformation with
      aberrant facial nerve: a case report.
AB  - Cochlear implantation is regarded as a safe surgery for young children with
      minimal complications. However, inner ear malformations and aberrant course of
      facial nerves may impede electrode insertion via the round window approach and
      increase the risk of iatrogenic facial nerve injury. We report a case of cochlear
      incomplete partition in a patient with anomalous facial nerve anatomy. The
      anterior and inferior displacement of the facial nerve obscured the round window.
      A retrofacial approach was used to expose the round window and the electrode was
      inserted successfully. No surgical complications were found postoperatively, and
      the child showed significant improvement in speech perception. As the course of
      the aberrant facial nerve is difficult to track preoperatively, surgeons should
      proceed with caution to reduce the risk of facial nerve injury during the
      operation.

PMID- 16417983
TI  - Multiphasic contrast-enhanced multidetector-row CT of liver: contrast-enhancement
      theory and practical scan protocol with a combination of fixed injection duration
      and patients' body-weight-tailored dose of contrast material.
AB  - The introduction of multidetector-row CT (MDCT) has provided the abdominal
      radiologists with dramatic changes for the imaging of the liver. At just present,
      establishment of new and optimal injection protocol in multiphasic contrast
      enhanced MDCT of the liver has been yearned because the difficulty and the
      importance to optimize the scan timing for each phase imaging have obviously
      increased because of the extremely rapid scan speed with MDCT scanners. Among
      technical factors employed in an injection protocol for multiphasic contrast
      enhanced MDCT of the liver, to make an injection duration of contrast material
      fixed is the most important for the precise estimation of the scan timing for
      each phase imaging. With the fixed injection duration, the peak enhancement time
      of the aorta, portal vein, and liver constantly appear approximately 10, 20, and
      30s after the any fixed injection durations (completion of injection of contrast
      material), respectively. Moreover, using a combination of the fixed injection
      duration and patients' body-weight-tailored dose of contrast material, similarity
      of time-density curves of each organ in shape and pattern can be achieved for
      individual patient with different body weight. In this issue, we will attempt to
      determine an ultimately optimal, but practical injection/scan protocol to
      successfully realize multiphasic contrast-enhanced MDCT of the liver based on the
      contrast-enhancement theory.

PMID- 16417984
TI  - Hyphenation of ultra performance liquid chromatography (UPLC) with inductively
      coupled plasma mass spectrometry (ICP-MS) for fast analysis of bromine containing
      preservatives.
AB  - Ultra performance liquid chromatography (UPLC) was coupled to inductively coupled
      plasma mass spectrometry (ICP-MS) for fast analysis of three bromine-containing
      preservatives, monitoring the 79Br and 81Br isotopes simultaneously. Due to the
      efficiency of the 1.7 microm column packing material, the resolution of the test
      substances was only slightly affected when the linear flow velocity was increased
      from 0.5 to 1.9 mm s(-1). However, the sensitivity of ICP-MS detection decreased
      when the linear flow velocity was increased from 0.5 to 1.9 mm s(-1). Analytical
      figures of merit were determined at an intermediate and at a high linear
      velocity. The precision was better than 2.2% R.S.D. and regression analysis
      showed that a linear response was achieved at both flow rates (R2 > 0.9993, n =
      36). The analysis time was less than 4.5 min at a flow rate of 50 microL min(-1)
      and limits of detection and quantification were better than 3.3 and 11 microg
      BrL(-1), respectively. The analysis time was reduced to 2.7 min when the flow
      rate was increased to 90 microL min(-1) and limits of detection and
      quantification were better than 20 and 65 microg BrL(-1), respectively. The
      method was applied for quantitative analysis of bromine-containing preservatives
      in commercially available cosmetic products.

PMID- 16417985
TI  - The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE): further
      description and extended norms.
AB  - BACKGROUND: The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)
      was introduced in 1995 as a four-scale questionnaire for measuring psychosis
      proneness, principally schizotypy. Its items were deliberately chosen to make it
      suitable for tapping psychotic characteristics in healthy individuals. Since its
      inception the O-LIFE has been used in a wide variety of experimental and clinical
      studies, establishing its reliability and validity. METHODS: Data was pooled from
      1926 participants together with available demographic information from several
      research institutions. RESULTS: Extensive norms are presented by age and gender.
      Inter-correlations and regression equations based on age and gender are also
      presented. CONCLUSIONS: The theoretical background and implications of work on
      using the O-LIFE are briefly discussed.

PMID- 16417986
TI  - Increased rate of birth complications and small head size at birth in winter-born
      male patients with schizophrenia.

PMID- 16417987
TI  - The 'who' and 'when' of context memory: different patterns of association with
      auditory hallucinations.

PMID- 16417988
TI  - Characterisation of laboratory-generated vancomycin intermediate resistant
      Staphylococcus aureus strains.
AB  - Vancomycin has been the drug of choice for 30 years for the treatment of
      methicillin-resistant Staphylococcus aureus (MRSA). Emergence of decreased
      vancomycin susceptibility in MRSA strains presents a significant clinical problem
      with few therapeutic options. This study was performed to generate and
      characterise S. aureus strains with reduced susceptibility to vancomycin.
      Eighteen S. aureus strains were subjected to serial passaging on vancomycin to
      generate vancomycin intermediate resistant S. aureus (VISA) strains. Minimum
      inhibitory concentration (MIC) determination was performed for the parent and the
      passaged cultures with 13 different antibiotics. The strains were tested by the
      following five methods: simplified population analysis; CDC method; modified
      vancomycin agar screen; population analysis profile (PAP); and modified
      population analysis (PAP-area under the curve (AUC) ratio). Phenotypic changes
      such as doubling time, synergy with beta-lactam antibiotics and effect on norA
      efflux pumps were also studied for these strains. The result indicated that 8
      VISA mutants (vancomycin MICs, 8-16 microg/mL) were generated in vitro from the
      18 S. aureus strains. The CDC and modified agar methods proved to be the most
      sensitive and specific methods for detection of VISA strains. The PAP for all the
      VISA strains ranged from 12 microg/mL to > 16 microg/mL, with a PAP-AUC ratio of
      > 1.3. All mutants showed increased doubling time compared with their parent
      isolate. Synergism of the vancomycin and beta-lactam combinations was observed
      for all methicillin-resistant mutants. Upon acquisition of vancomycin resistance,
      a few mutants showed decreased oxacillin resistance. Two VISA strains were chosen
      for molecular characterisation of the mecA gene and one mutant showed genotypic
      changes with deletion of mecA. Loss of norA efflux pumps leading to
      fluoroquinolone sensitivity was also observed in four mutants.

PMID- 16417989
TI  - Advances in the management of sepsis: the randomised controlled trials behind the
      Surviving Sepsis Campaign recommendations.
AB  - The Surviving Sepsis Campaign is the first international, multiorganisation,
      multidisciplinary attempt to reduce the appalling morbidity and mortality related
      to sepsis. Under the auspices of the campaign, guidelines have been published
      that cover more than 50 aspects of care of the septic patient. Campaign
      guidelines on antimicrobial therapy cover very general aspects of antibiotic
      policy and are mostly supported by expert opinion rather than randomised
      controlled trials. However, these 'common sense' recommendations on antibiotic
      therapy have been included in this review. The core areas of the Surviving Sepsis
      Campaign guidelines have been crystallised into resuscitation and management
      'bundles'. This review focuses on the most important clinical trials that form
      the basis of these core guidelines.

PMID- 16417990
TI  - In vitro activity of sitafloxacin compared with several fluoroquinolones against
      Streptococcus anginosus and Streptococcus constellatus.
AB  - The in vitro activities of sitafloxacin and seven other fluoroquinolones a
      (ciprofloxacin, tosufloxacin, sparfloxacin, levofloxacin, T-3811ME, moxifloxacin
      and trovafloxacin) were examined by the microdilution method against 79
      clinically isolated 'Streptococcus milleri' group (SMG) microorganisms. No
      statistically significant differences were found between the minimum inhibitory
      concentrations (MIC(50) and MIC(90)) against Streptococcus anginosus and
      Streptococcus constellatus. Sitafloxacin was the most active agent of the eight
      fluoroquinolones tested against SMG, with a MIC(90) of 0.06 microg/mL, which was
      8 times more active than ciprofloxacin and 16 times more active than
      levofloxacin. Although none of the SMG strains showed high resistance to any of
      the fluoroquinolones tested, three agents (trovafloxacin, sitafloxacin and T
      3811ME) had low MICs against 23 SMG strains against which levofloxacin had a MIC>
      1 microg/mL. In conclusion, several fluoroquinolones have low MICs against SMG,
      but sitafloxacin has the lowest.

PMID- 16417991
TI  - Resistance to three antimicrobial agents of Campylobacter isolated from
      organically- and intensively-reared chickens purchased from retail outlets.
AB  - Resistance rates to three antimicrobials (ciprofloxacin, erythromycin and
      nalidixic acid) in Campylobacter isolated from organically- and intensively
      reared chickens purchased from supermarkets and butcher's shops in London were
      determined. Significant differences in the minimum inhibitory concentrations
      (MICs) of nalidixic acid were found, with the highest values in unpackaged
      intensively-reared chickens and the lowest values in organically-reared chickens.
      Using pre-set breakpoints, all isolates from all groups of chickens were
      identified as resistant to erythromycin and nalidixic acid. All isolates from the
      organically-reared group were susceptible to ciprofloxacin. Of the supermarket
      intensively-reared chickens, 8.7% harboured resistant isolates, all on the
      external parts, indicating post-slaughtering contamination. The highest
      percentage (26.7%) was in chickens from butcher shops, mostly in the chicken
      cavities, suggesting a link to treatment on the farm.

PMID- 16417992
TI  - Assay of ertapenem in human serum by high-performance liquid chromatography.
AB  - Ertapenem is a new carbapenem with a broad spectrum of activity and an extended
      half-life, permitting once daily administration. Although high-performance liquid
      chromatography (HPLC) methods have been described for ertapenem, these are
      complex and involve column switching and thus this type of assay may not suitable
      for use in routine clinical microbiology laboratories. In this study we report a
      rapid, straightforward HPLC method for the detection of ertapenem in human serum.

PMID- 16417993
TI  - Appropriateness of glycopeptide use in a hospital in Italy.
AB  - The aims of this study were to quantify the rate of inappropriate glycopeptide
      use. The study was carried out by reviewing all medical records of patients who
      received a glycopeptide in a hospital located in Italy. A total of 452 patients
      received glycopeptides, with a rate of inappropriate use of 90.9%.
      Appropriateness of glycopeptide prescriptions was significantly higher in
      Intensive Care Units compared with surgical wards (odds ratio (OR) = 0.03; 95%
      confidence interval (CI) = 0.01-0.14), in younger patients (OR = 0.97; 95% CI =
      0.95-0.99) and in those patients who received the prescription for therapy rather
      than prophylaxis (OR = 0.2; 95% CI = 0.06-0.66). Models were also developed to
      predict appropriateness of glycopeptide indications for therapy and prophylaxis.
      The information obtained in our audit may enable development of strategies to
      improve physician prescribing patterns.

PMID- 16417994
TI  - The plasma membrane Ca2+-ATPase protein from red blood cells is not modified in
      preeclampsia.
AB  - Plasma membrane Ca2+-ATPase activity diminishes by about 50% in red blood cells
      during preeclampsia. We investigated whether the number of Ca2+-ATPase molecules
      is modified in red cell membranes from preeclamptic pregnant women by measuring
      the specific phosphorylated intermediate of this enzyme. Also, we isolated the
      Ca2+-ATPase protein from both normotensive and preeclamptic pregnant women and
      estimated its molecular weight, and its cross-reactions with specific polyclonal
      and monoclonal (5F10) antibodies against it. We measured the Ca2+-ATPase activity
      in a purified state and the effect of known modulators of this ATPase. It was
      found that the phosphorylated intermediate associated with PMCA is similar for
      red cell ghosts from normotensive and preeclamptic women, suggesting a similar
      number of ATPase molecules in these membranes. The molecular weight of the Ca2+
      ATPase is around 140 kDa for both normotensive and preeclamptic membranes, and
      its cross-reactions with specific antibodies is similar, suggesting that the
      protein structure remains intact in preeclampsia. Calmodulin, ethanol, or both
      calmodulin plus ethanol, stimulated the Ca2+-ATPase activity to the same extent
      for both normotensive and preeclamptic preparations. Our results showed that the
      reduced Ca2+-ATPase activity of the red cell membranes from preeclamptic women is
      not associated with a defective enzyme, but rather with a high level of lipid
      peroxidation.

PMID- 16417995
TI  - Characterization of oxalic acid derivatives as new metabolites of metamizol
      (dipyrone) in incubated hen's egg and human.
AB  - Metamizol (dipyrone, 1), a widely used drug with effective analgesic and
      antispasmodic properties, shows severe side effects like agranulocytosis and
      anaphylactic shock reactions, the reasons of which are not known until today.
      After oral administration 1 is completely metabolized. All hitherto known
      metabolites have an intact pyrazolinone ring structure like the parent compound
      and are completely extractable from urine with polar organic solvents. However,
      only a fractional amount of the applied dosage can be recovered by this
      procedure. To clarify the reason of this deficit of unknown metabolites we
      followed the hypothesis of oxidative rupture of the heterocyclic ring during
      metabolism of 1. On the basis of former in vitro results we now were able to
      identify in quality three oxalic acid derivatives and one acetic acid
      phenylhydrazide as new metabolites of metamizol in the allantoic fluid (AF) of
      incubated hen's eggs as well as in human urine by means of GC-MS analysis and
      comparison with unequivocally synthesized authentic reference compounds. Whereas
      the oxamazide 7, the phenylhydrazide 8 and N-methyloxamic acid 9 are only present
      in trace concentrations and therefore cannot account for the deficit in the
      balance of metabolites, the oxalic acid monohydrazide 11 seems to be excreted in
      higher amount. But quantitative determination of this new metabolite would be
      required to answer the open questions concerning the biotransformation of
      metamizol and thereby to detect new facts about mode of action and side effects
      of this drug.

PMID- 16417996
TI  - [Pain in neonates: pharmacological treatment].
AB  - Pain causes numerous physiological changes in neonates. All invasive procedures
      induce undesirable stress responses; theses responses can, however, be eliminated
      or reduced by a judicious use of analgesia. Even though a large number of
      analgesics and sedatives are currently available, most of them have not been
      studied in the neonate. At present, a precise understanding of the
      pharmacological mechanisms of analgesics is difficult because many interactions
      still remain unknown in the term and premature neonate. This article describes
      the main analgesics and sedative agents used in the neonate: morphine, fentanyl,
      sufentanil, alfentanil, nalbuphine, ketamine, midazolam, propofol, acetaminophen,
      and Emla cream. After a review of the literature regarding these drugs, some
      practical advices and suggestions for the treatment of procedure-induced pain,
      and background sedation/analgesia for ventilated neonates are given. It is also
      stated in this article that the best way to soothe pain in neonates is to combine
      non pharmacological and pharmacological strategies. At the national level,
      written guidelines should be prepared in order to improve pain management in the
      neonate.

PMID- 16417997
TI  - Analytics with engineered bacterial bioreporter strains and systems.

PMID- 16417998
TI  - Neural map specification by gradients.
AB  - Topographic maps, in which the spatial order of neurons maps smoothly onto their
      axonal target, are a central feature of neural wiring. Ephrins and Eph receptors
      are well accepted as graded labels for map development, enabling current studies
      into molecular principles of mapping. Ephrins regulate axon growth either
      positively or negatively, leading to models in which axons terminate at a neutral
      or optimum point in the gradient. Axonal competition ensures the target is
      filled. Ephrins and Ephs are typically expressed in complex overlapping patterns,
      with implications for signaling mechanisms, scale of internal map features, and
      coordinated interconnection of multiple mapping modules. Recent studies of Wnt3
      and En-2 show that topographic axon guidance cues may be as diverse as molecules
      previously regarded as morphogens and transcription factors.

PMID- 16417999
TI  - Heparan sulfate proteoglycans and the emergence of neuronal connectivity.
AB  - With the identification of the molecular determinants of neuronal connectivity,
      our understanding of the extracellular information that controls axon guidance
      and synapse formation has evolved from single factors towards the complexity that
      neurons face in a living organism. As we move in this direction - ready to see
      the forest for the trees - attention is returning to one of the most ancient
      regulators of cell-cell interaction: the extracellular matrix. Among many matrix
      components that influence neuronal connectivity, recent studies of the heparan
      sulfate proteoglycans suggest that these ancient molecules function as versatile
      extracellular scaffolds that both sculpt the landscape of extracellular cues and
      modulate the way that neurons perceive the world around them.

PMID- 16418000
TI  - Global and local mechanisms of forebrain and midbrain patterning.
AB  - During the past years, major advances have been made in understanding the
      sequential events involved in neural plate patterning. Positional information is
      already conferred to cells of the neural plate at the time of its induction in
      the ectoderm. The interplay between the BMP- and the Fgf- signaling pathways
      leads to the induction of neural cell fates. Thus, neural induction and neural
      plate patterning are overlapping processes. Later, at the end of gastrulation,
      positional cell identities within the neural plate are refined and maintained by
      the action of several neural plate organizers. By locally emitting signaling
      molecules, they influence the fate of the developing nervous system with high
      regional specificity. Recent advances have been made both in understanding the
      mechanisms that dictate the relative position of these organizers and in how
      signaling molecules spread from them with high spatial and temporal resolution.

PMID- 16418001
TI  - RNA binding proteins and the regulation of neuronal synaptic plasticity.
AB  - Cognitive function and memory rely on synaptic plasticity - the ability of
      synapses to modify their strength in response to stimulation. Emerging evidence
      indicates that post-transcriptional gene regulation is necessary for synaptic
      plasticity at several levels: by increasing proteome diversity through
      alternative splicing, or by enabling activity-dependent regulation of mRNA
      localization, translation or degradation in the dendrite. Mouse knockout studies
      have linked three RNA-binding proteins, fragile X mental retardation protein,
      cytoplasmic polyadenylation element binding factor and neuro-oncological ventral
      antigen to specific aspects of synaptic plasticity. Specificity in the regulation
      of synaptic plasticity might, in part, relate to the functional coherence of
      proteins encoded by the RNA targets of each RNA-binding protein.

PMID- 16418002
TI  - The evolving roles of axonally synthesized proteins in regeneration.
AB  - Work emerging during the past decade has shown that axons, similar to dendrites,
      are capable of autonomously generating new proteins through translation of
      localized mRNAs. Even in mammals, neurons maintain the ability to target mRNAs
      and translational machinery into the axonal compartment well into adulthood. The
      biological functions of axonal protein synthesis in adult neurons are just now
      being revealed, and recent studies indicate that locally synthesized proteins
      facilitate regeneration. Local translation, in addition to protein degradation,
      is needed for growth cone formation after axotomy, for generating a retrogradely
      transported injury signal, and then to help structurally maintain the growing
      axon. Regulation of axonal protein synthesis by exogenous stimuli might provide a
      means to facilitate regeneration for neuronal populations that normally show poor
      regenerative capacity in the adult nervous system.

PMID- 16418003
TI  - Longitudinal axon guidance.
AB  - Our knowledge about molecular mechanisms underlying axon guidance along the
      antero-posterior axis in contrast to the dorso-ventral axis of the developing
      nervous system is very limited. During the past two years in vitro and in vivo
      studies have indicated that morphogens have a role in longitudinal axon guidance.
      Morphogens are secreted proteins that act in a concentration-dependent manner on
      susceptible groups of precursor cells and induce their differentiation to a
      specific cell fate. Thus, gradients of morphogens are responsible for the
      appropriate patterning of the nervous system during early phases of neural
      development. Therefore, it was surprising to find that gradients of two of these
      morphogens, Wnt4 and Shh, can be re-used for longitudinal axon guidance during
      later stages of nervous system development.

PMID- 16418004
TI  - Ions generated from uranyl nitrate solutions by electrospray ionization (ESI) and
      detected with Fourier transform ion-cyclotron resonance (FT-ICR) mass
      spectrometry.
AB  - Electrospray ionization (ESI) of uranyl nitrate solutions generates a wide
      variety of positively and negatively charged ions, including complex adducts of
      uranyl ions with methoxy, hydroxy, and nitrate ligands. In the positive ion mode,
      ions detected by Fourier transform ion cyclotron resonance (FT-ICR) mass
      spectrometry are sensitive to instrumental tuning parameters such as quadrupole
      operating frequency and trapping time. Positive ions correspond to oligomeric
      uranyl nitrate species that can be characterized as having a general formula of
      [(UO(2))(n)(A)(m)(CH(3)OH)(s)](+) or [(UO(2))(n)(O)(A)(m)(CH(3)OH)(s)](+) with n
      = 1-4, m = 1-7, s = 0 or 1, and A = OH, NO(3), CH(3)O or a combination of these,
      although the formation of NO(3)-containing species is preferred. In the negative
      ion mode, complexes of the form [(UO(2))(NO(3))(m)](-) (m = 1-3) are detected,
      although the formation of the oxo-containing ions [(UO(2))(O)(n)(NO(3))(m)](-) (n
      = 1-2, m = 1-2) and the hydroxy-containing ions [(UO(2))(OH)(n)(NO(3))(m)](-) (n
      = 1-2, m = 0-1) are also observed. The extent of coordinative unsaturation of
      both positive and negative ions can be determined by ligand association/exchange
      and H/D exchange experiments using D(2)O and CD(3)OD as neutral reaction partners
      in the gas-phase. Positive ions are of varying stability and reactivity and may
      fragment extensively upon collision with D(2)O, CD(3)OD and N(2) in sustained off
      resonance irradiation/collision-induced dissociation (SORI-CID) experiments.
      Electron-transfer reactions, presumably occurring during electrospray ionization
      but also in SORI-CID, can result in reduction of U(VI) to U(V) and perhaps even
      U(IV).

PMID- 16418006
TI  - Sensitivity to effective relational complexity in the occipitoparietal lobe.
AB  - Previous work identified bilateral regions in the occipitoparietal lobe sensitive
      to the complexity of relational information [Phillips, S., Niki, K., 2003.
      Increased bilateral occipitoparietal activity for retention of binary versus
      unary indexed lists in pair recognition. NeuroImage 20 (2), 1226-1235]. Here, we
      investigate the effect of learning on sensitivity to relational complexity. Eight
      subjects were scanned on a pair recognition task before, during and after a 2
      week training period when subjects learned to recognize a set of shape pairs. For
      each trial of the pair recognition task, subjects determined whether a probe pair
      appeared in a list of learned or novel pairs. In the low/high relational
      complexity condition, every pair in list AB CD EF/AB AD CB was uniquely
      identifiable by an item in either/both the first or/and second position. Whole
      brain and region of interest contrasts revealed a significant interaction between
      complexity and learning in the occipitoparietal lobe. The increase in activity
      for the retention of high versus low complexity lists was greater for learned
      than novel pair lists. Subjects were more likely to respond to low complexity
      lists as though they were high complexity prior to training. The results suggest
      that this region provides a window into effective relational complexity, that is,
      complexity of relational information as processed by the subject, not as presumed
      by task design.

PMID- 16418007
TI  - The neural basis of implicit moral attitude--an IAT study using event-related
      fMRI.
AB  - Recent models of morality have suggested the importance of affect-based automatic
      moral attitudes in moral reasoning. However, previous investigations of moral
      reasoning have frequently relied upon explicit measures that are susceptible to
      voluntary control. To investigate participant's automatic moral attitudes, we
      used a morality Implicit Association Test (IAT). Participants rated the legality
      of visually depicted legal and illegal behaviors of two different intensity
      levels (e.g., high intensity illegal = interpersonal violence; low intensity
      illegal = vandalism) both when the target concept (e.g., illegal) was
      behaviorally paired with an associated attribute (e.g., bad; congruent condition)
      or an unassociated attribute (e.g., good; incongruent condition). Behaviorally,
      an IAT effect was shown; RTs were faster in the congruent rather than incongruent
      conditions. At the neural level, implicit moral attitude, as indexed by increased
      BOLD response as a function of stimulus intensity, was associated with increased
      activation in the right amygdala and the ventromedial orbitofrontal cortex. In
      addition, performance on incongruent trials relative to congruent trials was
      associated with increased activity in the right ventrolateral prefrontal cortex
      (BA 47), left subgenual cingulate gyrus (BA 25), bilateral premotor cortex (BA 6)
      and the left caudate. The functional contributions of these regions in moral
      reasoning are discussed.

PMID- 16418008
TI  - Aquaporins in chicken: localization of ck-AQP5 along the small and large
      intestine.
AB  - Aquaporins (AQPS) are transmembrane water channels poorly investigated in birds.
      Using degenerated primers and RT-PCR, we identified in kidney and
      gastrointestinal tract of Hubbard chickens (Gallus gallus) three fragments,
      corresponding to ck-AQP2, ck-AQP4, and ck-AQP5 mRNAs. Comparison of nucleotide ck
      AQPs sequences to their rat and human orthologues revealed an overall identity of
      75-90%. Expression in the renal and gastrointestinal systems of the three ck-AQPs
      mRNA was analysed by Northern assays. Transcript of ck-AQP2 was only identified
      in kidney. ck-AQP4 mRNA was highly expressed in brain, and to a lesser extent in
      kidney and stomach. ck-AQP5 mRNA was found in jejunum and ileum, and to a lesser
      extent in colon and lung. In situ hybridisation showed ck-AQP5 mRNA in the crypt
      cells of jejunum, ileum and colon, whereas it was absent from the cells lining
      the villi. Levels of ck-AQP5 mRNA (analyzed by Northern and in situ hybridisation
      assays) and protein (analysed by immunohistochemistry) decreased from the jejunum
      to the colon. This work confirmed the presence of AQPs in chicken, and showed
      that chicken and mammalian AQPs share a high degree of similarity in nucleotide
      sequence and tissue distribution.

PMID- 16418009
TI  - The amplified peptidome: the new treasure chest of candidate biomarkers.
AB  - Mass spectrometric analysis of the low-molecular weight (LMW) range of the
      serum/plasma proteome is revealing the existence of large numbers of previously
      unknown peptides and protein fragments predicted to be derived from low-abundance
      proteins. This raises the question of why such low abundance molecules would be
      retained at detectable levels in the circulation, instead of being rapidly
      cleared and excreted. Theoretical models of biomarker production and association
      with serum carrier proteins have been developed to elucidate the mechanisms
      governing biomarker half-life in the bloodstream. These models predict that the
      vast majority of LMW biomarkers exist in association with circulating high
      molecular mass carrier proteins. Moreover, the total serum/plasma concentration
      of the biomarker is largely determined by the clearance rate of the carrier
      protein, not the free-phase biomarker clearance itself. These predictions have
      been verified experimentally using molecular mass fractionation of human serum
      before mass spectrometry sequence analysis. These principles have profound
      implications for biomarker discovery and measurement.

PMID- 16418010
TI  - Biomarker discovery from the plasma proteome using multidimensional fractionation
      proteomics.
AB  - Because biomarkers are typically low in abundance, the crucial step of biomarker
      discovery is to efficiently separate clinically relevant sets of proteins that
      might define disease stages and/or predict disease development. It is anticipated
      that a multi-dimensional fractionation system (MDFS) will provide an efficient
      means of separating low abundance proteins from plasma proteins, resulting in the
      extension of the detection limit. However, when using an MDFS to analyze the
      plasma proteome it is important to consider how sample processing, yield,
      resolution and throughput potential may influence the detection limit. This
      review evaluates the recent advances in MDFS research with respect to '4RS
      criterion' (4R: resolution, reproducibility, recovery, and robustness; 4S:
      simplicity, speed, selectivity and sensitivity) and discusses perspectives for
      future plasma-derived biomarker discovery.

PMID- 16418011
TI  - Nanotechnologies for biomolecular detection and medical diagnostics.
AB  - Nanotechnology-based platforms for the high-throughput, multiplexed detection of
      proteins and nucleic acids in heretofore unattainable abundance ranges promise to
      bring substantial advances in molecular medicine. The emerging approaches
      reviewed in this article, with reference to their diagnostic potential, include
      nanotextured surfaces for proteomics, a two-particle sandwich assay for the
      biological amplification of low-concentration biomolecular signals, and silicon
      based nanostructures for the transduction of molecular binding into electrical
      and mechanical signals, respectively.

PMID- 16418012
TI  - Fluorescent labels for proteomics and genomics.
AB  - Fluorescent labeling reagents are an essential component of a huge industry built
      on sensitive fluorescence detection. This technology has grown over 30 years and
      is in some ways mature. Excellent labeling reagents with close to maximum
      theoretical brightness are available in many different colors. Large fluorescent
      proteins like phycobiliproteins are also widely used that are exceedingly bright.
      Other fluorescent proteins like the GFP family can be obtained for creating
      genetically encoded protein labels in living cells. A new 'solid state' quantum
      dot technology is being exploited for large-scale multiparameter labeling. This
      technology provides the 'ultimate' photostable labeling reagent. Still, there are
      advances to be made. Not available is the ultimate tool kit of low molecular
      weight, strongly light absorbing, photostable labels with narrow emission bands
      ranging from the UV to the IR.

PMID- 16418014
TI  - Detection of 16S rRNA gene in round bodies isolated from polyps of
      rhinosporidiosis.
AB  - Polyps of rhinosporidiosis contain microscopic round bodies, believed to be
      causative agents of the disease. The source and identity of these round bodies
      has been debated ever since the first case was described in the year 1900. Most
      patients have a history of exposure to pond water. Collection and microscopic
      analysis of pond water samples where patients had been dipping led to the idea
      that a cyanobacterium could possibly develop into round bodies after entering the
      patient's nose. Molecular genomic studies based on PCR, cloning, and sequencing
      were, therefore, carried out using purified DNA, extracted from individually
      separated round bodies from polyp samples. Parallel investigations were also
      conducted on DNA extracted from cyanobacterium Microcystis isolated from pond
      water samples. The results of these experiments presented here provide evidence
      of the presence of 1458 bp 16S rRNA gene in round bodies. This is the first
      molecular study indicating the prokaryotic identity of round bodies in
      rhinosporidiosis.

PMID- 16418013
TI  - Wild type and YMDD variant of hepatitis B virus: no difference in viral kinetics
      on lamivudine/tenofovir therapy in HIV-HBV co-infected patients.
AB  - Prolonged lamivudine therapy has been identified as the major risk for the
      development of resistance in HBV, with rates of 90% after 4 years of treatment.
      Tenofovir disoproxil fumarate showed activity against both wild type and
      lamivudine resistant HBV in HIV-HBV co-infected patients. In order to compare the
      efficacy of lamivudine/tenofovir treatment we investigated detailed HBV kinetics
      in 13 HIV-HBV co-infected patients with either wild type HBV or lamivudine
      resistant HBV. The viral strains in both patient groups showed a biphasic viral
      decline pattern. Only in the first phase of viral decay, which reflects the
      clearance rate of the free virus from plasma, there was a statistically
      significant response in favor of the wild type group. After the first phase we
      observed a similar viral decline till 24 weeks of both groups. This is reassuring
      for many pretreated co-infected patients harbouring mutant viruses.

PMID- 16418015
TI  - Immunochemical, ultrastructural and electrophysiological investigations of bone
      derived stem cells in the course of neuronal differentiation.
AB  - Numerous reports have highlighted the use of mesenchymal stem cells (MSC) for
      tissue engineering because of the capacity of the cells to differentiate along
      the osteogenic, chondrogenic or adipogenic pathway. As MSC also display neuronal
      morphologies under appropriate culture conditions, the differentiation capacity
      of stem cells seems to be more complex than initially thought, but it requires
      careful characterization of the cells. This is especially the case because
      recently it has been suggested that neuronal differentiation of stem cells is
      only an artifact. Here, we investigate the sequence of ultrastructural changes of
      bone-derived stem cells during neuronal induction and compare these data with
      immunocytochemical and electrophysiological properties of the cells. For further
      comparative analyses, stem cells were incubated with non-neurologically inducing
      stressors. The stem cells were harvested from human osseous debris and were
      characterized morphologically, immunocytochemically and by using FACS. After 6 h
      of neuronal induction, the cells had assumed neuronal morphologies and expressed
      neuron-specific enolase, beta-III-tubulin, neurofilament-H and HNK-1, while only
      a subpopulation expressed CD15 and synaptophysin. However, electrical signaling
      could not be detected, neither spontaneously nor after electrical stimulation.
      Nevertheless, transmission electron microscopy revealed cellular features of
      neuritogenesis and synaptogenesis in the course of neuronal induction and
      suggested that the cells have features similar to those observed in immature
      neurons. Based upon the results, it can be concluded that neuronal induction had
      initiated the early steps of neuronal differentiation, while exposure of the
      cells to non-neurological stressors had caused necrotic alterations.

PMID- 16418016
TI  - Preventing chronic pain after surgery: who, how, and when?

PMID- 16418017
TI  - 30 plus years--an anniversary celebration of ASRA and regional anesthesia and
      pain medicine.

PMID- 16418018
TI  - The effect of cyclooxygenase-2 inhibition on acute and chronic donor-site pain
      after spinal-fusion surgery.
AB  - BACKGROUND AND OBJECTIVES: The development of chronic pain after spinal-fusion
      surgery represents a significant source of morbidity. One of the predictive
      factors for the development of chronic postsurgical pain is inadequate acute
      postoperative pain management. Further, the up-regulation of cyclooxygenase-2
      (COX-2) after surgery may result in neuro-plastic changes that may contribute to
      a progression from acute to chronic pain. The goal of this prospective,
      randomized, double-blind study was to examine the effect of perioperative COX-2
      inhibition on acute and chronic donor-site pain in patients undergoing spinal
      fusion surgery. METHODS: Eighty patients scheduled to undergo instrumented
      posterior spinal fusion were randomized to either receive celecoxib 400 mg 1 hour
      before surgery, and then 200 mg every 12 hours after surgery for the first 5 days
      or receive matching placebo at similar time intervals. Patients were administered
      morphine via patient-controlled analgesia pump for the first 24 hours, and then
      acetaminophen and oxycodone tablets. Patients were asked to quantify their
      average pain on postoperative days 1 to 5. At 1 year after surgery, patients were
      questioned about the presence and subjective characteristics of any residual
      donor-site pain. RESULTS: Patients administered celecoxib reported lower pain
      scores and less opioid use during the first 5 postoperative days. Chronic donor
      site pain was significantly higher (P<.01) in the placebo group (12 of 40, or
      30%) compared with the celecoxib group (4 of 40, or 10%) at 1 year after surgery.
      CONCLUSIONS: The administration of celecoxib for the first 5 days after spinal
      fusion surgery resulted in improved analgesia and a reduction in chronic donor
      site pain at 1 year after surgery.

PMID- 16418019
TI  - Efficacy of lidocaine or bupivacaine combined with ephedrine in rat sciatic nerve
      block.
AB  - BACKGROUND AND OBJECTIVES: The adrenergic drug ephedrine inhibits Na(+) current
      in cultured cells expressing Na(+) channels and provides dose-dependent
      reversible rat sciatic nerve blockade. The dosage required for peripheral nerve
      blockade in humans would cause unacceptable cardiovascular side effects. We
      therefore hypothesized that either lidocaine or bupivacaine would show synergy
      with ephedrine in a rat sciatic nerve block model, allowing a dose reduction and
      limiting side effects while improving efficacy. METHODS: Sciatic nerves of
      anesthetized rats were exposed by lateral incision of the thighs; 0.2 mL of
      different concentrations of the following drugs was injected sub-fascially:
      bupivacaine, lidocaine, and ephedrine alone and bupivacaine or lidocaine combined
      with ephedrine (n=8 per group). After animals recovered from anesthesia, a
      blinded investigator evaluated motor blockade (push against a balance) and
      sensory/nociceptive blockade (to pinch of the fifth toe) at predefined time
      intervals. RESULTS: Ephedrine combined with bupivacaine interacted additively for
      both motor and sensory blockade, and ephedrine combined with lidocaine interacted
      antagonistically (sub-additive) for sensory blockade and additively for motor
      blockade. CONCLUSIONS: A combination of ephedrine with either lidocaine or
      bupivacaine is unlikely to allow a significant dose reduction because of a lack
      of synergy. Furthermore, the cardiovascular side effects will limit the maximal
      tolerable dosage of ephedrine.

PMID- 16418020
TI  - In vitro antagonism of recombinant ligand-gated ion-channel receptors by
      stereospecific enantiomers of bupivacaine.
AB  - BACKGROUND AND OBJECTIVES: Bupivacaine is a racemic mixture of S(-)- and R(+)
      enantiomers. Both isomers have similar potency as local anesthetics, but the S(-)
      enantiomer produces less central nervous system and cardiovascular toxicity.
      Local anesthetic-induced convulsion is likely to be associated with not only
      sodium channel but also ligand-gated ion channel. The present study investigates
      the direct effects of the stereoenantiomers of bupivacaine on 4 recombinant
      ligand-gated ion-channel receptors. METHODS: The antagonist activities of the S(
      )- and R(+)-enantiomers of bupivacaine were tested at the nicotinic
      acetylcholine, N-methyl-d-aspartate (NMDA), gamma-aminobutyric acid(A) (GABA(A)),
      and 5-hydroxytryptamine(3A) (5-HT(3A)) receptors expressed in Xenopus oocytes
      using a 2-voltage clamp technique. RESULTS: Racemic bupivacaine and its 2
      enantiomers all antagonized the 4 receptors in a concentration-dependent manner.
      Potencies at nicotinic acetylcholine, NMDA, and 5-HT(3A) receptors were similar.
      At GABA(A) receptors, the potency of R(+)-bupivacaine was less than racemic
      bupivacaine or levobupivacaine. CONCLUSIONS: Comparison of the antagonist
      potencies with local concentrations obtained in clinical use suggests that
      bupivacaine and its enantiomers are likely to produce extensive inhibition at the
      nicotinic acetylcholine, NMDA, and 5-HT(3A) receptors but a much weaker and
      probably not clinically relevant effect at the GABA(A) receptor. It is possible
      that direct effects at these receptors may contribute, at least in part, to the
      spinal and epidural anesthesia induced by these compounds. It is unlikely,
      however, that the difference of the toxicity in bupivacaine enantiomers is
      because of the stereoselectivities of bupivacaine at ligand-gated ion-channel
      receptors studied.

PMID- 16418021
TI  - Efficacy of intra-articular bupivacaine, ropivacaine, or a combination of
      ropivacaine, morphine, and ketorolac on postoperative pain relief after
      ambulatory arthroscopic knee surgery: a randomized double-blind study.
AB  - BACKGROUND: Effective pain relief is important after diagnostic and therapeutic
      arthroscopic knee surgery to permit early discharge and improve comfort and
      mobility at home. The aim of this study was to assess the efficacy of
      bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and
      ketorolac injected intra-articularly for postoperative pain relief after
      arthroscopic knee surgery. METHODS: Sixty-three healthy patients undergoing knee
      arthroscopy under local anesthesia (LA) were randomized to receive 1 of the
      following substances intra-articularly postoperatively: group B: 30 mL of
      bupivacaine (150 mg); group R: 30 mL of ropivacaine (150 mg); and group RMK:
      ropivacaine 150 mg, morphine 4 mg, and ketorolac 30 mg in normal saline (total
      volume 30 mL). Oral paracetamol 1g and tramadol 50 mg were used as rescue drugs.
      Postoperatively, pain was assessed at rest and movement, and side effects were
      recorded. The patients were asked to self-assess pain for 7 days and record
      analgesic consumption as well as activities of daily living (ADLs). Plasma
      concentration of LA was measured in another 8 patients. RESULTS: All groups had
      excellent analgesia at 0 and 4 hours postoperatively. Group RMK had significantly
      lower visual analog pain score at rest at 8 hours and during movement at 8 and 24
      hours compared with the other groups (P<.05). Group RMK required less paracetamol
      and tramadol on day 1 (P<.05), had less sleep disturbances because of pain, more
      patients were ready to work on days 1 and 2 (P<.05), and were more satisfied on
      days 1 and 4 to 7. Postoperatively, plasma concentrations of ropivacaine and
      lidocaine were far below known systemic toxic concentrations in all patients.
      CONCLUSION: Addition of morphine and ketolorac to ropivacaine intra-articularly
      enhances analgesic efficacy of LA, reduces postdischarge analgesic consumption,
      and improves ADLs without increasing side effects after ambulatory arthroscopic
      knee surgery.

PMID- 16418022
TI  - The bilateral superficial cervical plexus block with 0.75% ropivacaine
      administered before or after surgery does not prevent postoperative pain after
      total thyroidectomy.
AB  - BACKGROUND AND OBJECTIVES: Patients undergoing thyroid surgery need postoperative
      pain management. Bilateral superficial cervical plexus block by administration of
      0.25% bupivacaine with 1:200000 epinephrine at the end of surgery has been shown
      to improve postoperative analgesia. The objective of this study was to assess the
      analgesic efficacy in the first 36 postoperative hours after total thyroidectomy
      of bilateral superficial cervical plexus block with 0.75% ropivacaine
      administered before the incision or on completion of the surgical procedure.
      METHODS: We performed a prospective double-blinded, randomized controlled trial
      that compared 3 parallel groups: the CONT group did not receive any block, the
      PRE group received bilateral superficial cervical plexus block before surgery
      while under general anesthesia, and the POST group received bilateral superficial
      cervical plexus block after surgery while under general anesthesia. The study
      included 111 patients (37 in each group). Postoperative pain was assessed every 4
      hours by use of a 0 to 10 numeric rating scale. All patients received paracetamol
      every 6 hours. Morphine was administered following a standardized protocol if the
      numeric rating scale was 4 or higher. The main outcome variables were the
      proportion of patients given morphine during the 36 hours period, pain intensity
      scores, and morphine consumption. RESULTS: No intergroup differences were
      observed in terms of percentage of patients who required morphine, morphine
      delivery, pain scores, and intraoperative opioid consumption. CONCLUSIONS:
      Bilateral superficial cervical plexus block with 0.75% ropivacaine administered
      before or after surgery does not improve postoperative analgesia after total
      thyroidectomy.

PMID- 16418023
TI  - Comparison of ondansetron and meperidine for prevention of shivering in patients
      undergoing spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Perioperative hypothermia is a common problem in
      anesthesia practice. Regional anesthesia, like general anesthesia, influences the
      thermoregulatory process. The aim of our study was to compare the efficacy of
      ondansetron and meperidine in the prevention of shivering during and after spinal
      anesthesia. METHODS: In this double-blind study, 75 patients were randomized into
      3 groups. Group O and Group M were given ondansetron 8 mg and meperidine 0.4
      mg/kg intravenously immediately before spinal anesthesia, respectively. Group C
      received saline at identical times. The core temperatures and the incidence of
      shivering were recorded. Association between maximum block height and mean rectal
      temperatures of the patients were also evaluated. RESULTS: The core temperature
      was preserved in both ondansetron and meperidine groups with respect to the
      control group. Shivering was observed in 8% of patients in groups O and M and 36%
      in group C. The correlation between maximum block height and mean rectal
      temperatures was lost in the ondansetron and meperidine groups. CONCLUSION:
      Ondansetron and meperidine have similar anti-shivering effects. In addition, both
      ondansetron and meperidine altered the correlation between the core temperature
      and block level during spinal anesthesia.

PMID- 16418025
TI  - Labat lecture 2005: surgical stress and postoperative outcome-from here to where?

PMID- 16418026
TI  - The American Society of Regional Anesthesia: a concise history of the original
      group-its birth, growth, and eventual dissolution.
AB  - The history of the original American Society of the Regional Anesthesia is
      presented-its birth, growth, and eventual dissolution. Reasons for its
      dissolution are discussed.

PMID- 16418027
TI  - White Knight: ASRA, ASA, and the formation of the ABA.
AB  - The original American Society of Regional Anesthesia (1924-1940) was instrumental
      in the formation of the American Board of Anesthesiology, whereupon competence in
      anesthesiology was placed on the same footing as every other specialty practice
      in the United States.

PMID- 16418028
TI  - Alon P. Winnie, L. Donald Bridenbaugh, jr., Harold Carron, P. Prithvi Raj, and
      Jordan Katz: founding fathers of the American Society of Regional Anesthesia.

PMID- 16418029
TI  - Pain medicine and regional anesthesia: inseparable roles?

PMID- 16418030
TI  - An injection from the past: fluoroscopic evidence of remote injections of
      radiopaque substances.
AB  - OBJECTIVE: Although uncommon, residual effects from contrast agents used more
      than 2 decades ago are possible. This case report is to alert clinicians to the
      implications of residual oil-based ionic contrast agents in the intrathecal
      space. CASE REPORT: A 70-year-old female with evidence of degenerative disc
      disease underwent a series of lumbar epidural steroid injections. Fluoroscopy
      during the procedure revealed diffuse residual intrathecal iophendylate
      (Pantopaque) dye. We were able to demonstrate unrestricted epidural spread of 1
      mL iohexol (Omnipaque 180) alongside the preexisting dye. CONCLUSIONS: The goal
      of this case report is to highlight the potential of residual myelographic dye to
      complicate interventional procedures. Such residual dye can increase the level of
      difficulty in performing interventional pain treatments and perhaps the rate of
      complications associated with epidural injections, such as dural puncture. The
      presence of large amounts of residual oil-based intrathecal dye can lead to
      erroneous interpretations of the dye patterns as intraspinal lipoma or
      hemorrhage. As a consequence, the patient can be submitted to unnecessary
      diagnostic and therapeutic interventions. In addition, concerns of worsening oil
      based dye-induced arachnoiditis with the use of epidural steroid injections can
      complicate the treatment of patients with back pain.

PMID- 16418032
TI  - Lateral sagittal infraclavicular block (LSIB).

PMID- 16418034
TI  - Ultrasound-guided cervical periradicular injection: cautious optimism.

PMID- 16418035
TI  - Is ultrasound necessary for routine axillary block?

PMID- 16418037
TI  - Clinical efficacy of the brachial plexus block via the posterior approach.

PMID- 16418038
TI  - What is cun?

PMID- 16418039
TI  - The transversus abdominis plane (TAP) block in open retropubic prostatectomy.

PMID- 16418040
TI  - Aspects of femoral nerve block.

PMID- 16418043
TI  - Variation in relative fat distribution associated with maturational timing: The
      Wroclaw Growth study.
AB  - Complete longitudinal data of 136 boys aged 8-16 years and 124 girls aged 8-15
      years were used to evaluate the association between maturational timing and the
      relative distribution of subcutaneous adipose tissue, specifically a trunk
      oriented pattern of distribution. Age at peak height velocity (PHV) was the
      indicator of maturational timing and three skinfolds (triceps, subscapular,
      abdomen) were the indicators of subcutaneous fatness. Principal components
      analysis of the three skinfolds was used to identify indicators of relative
      subcutaneous adipose tissue distribution. Age at PHV and chronological age
      significantly influenced scores on the first principal components, which
      indicated centripetal fat patterning. The data suggest that early maturing
      subjects accumulate more subcutaneous adipose tissue on the lower trunk compared
      with later maturing peers of the same age and sex.

PMID- 16418044
TI  - Factors associated with the pattern of breastfeeding in the north of Iran.
AB  - BACKGROUND: The health benefits of breastfeeding to infants and mothers have been
      well established. Its pattern varies between populations and the differences may
      originate from varying social and cultural factors. AIMS: The aims of this study
      were to determine the pattern of breastfeeding and to assess its determinants in
      a population-based study in Babol, in the north of Iran. SUBJECTS AND METHODS: A
      cross-sectional study of 600 randomly selected mothers with infants 12-24 months
      old was conducted in the north of Iran in 1998. Data concerning breastfeeding
      status, breastfeeding duration and social and demographic factors were collected
      through interviews with the mothers. The probability of continuation of
      breastfeeding (i.e. survival probability) was estimated by using the non
      parametric Kaplan-Meier method of survival analysis. The Cox regression analysis
      was applied to determine the factors associated with duration of breastfeeding.
      RESULTS: The results showed that the incidence of breastfeeding was 87 and 89% at
      12 months in urban and rural areas and 18 and 53% at 24 months, respectively. The
      difference in the pattern of breastfeeding between urban and rural areas was
      significant after 12 months (p=0.04). The Cox regression model analysis showed
      that living in a rural area, increment of birth order, higher education level of
      mothers, and being housewife mothers were associated with longer duration of
      breastfeeding. Although, in the univariate analysis, women with high education
      appeared to have shorter duration of breastfeeding in comparison with illiterate
      mothers, after controlling the effect of mother's working status and other
      variables using the Cox regression model, high level of education had a positive
      association with longer duration of breastfeeding, i.e. the risk of weaning was
      decreased in comparison with illiterate women. Also, the risk of shorter duration
      of breastfeeding was increased significantly among mothers with a high level of
      stress. The results did not show a significant difference in pattern of
      breastfeeding in relation to age of mothers and sex of infants. CONCLUSION:
      Although the rate of breastfeeding among mothers in Babol was increasing, greater
      health education efforts are needed to support and promote the healthy practice
      of breastfeeding, especially among the young, less educated, nullipara, in urban
      areas and among women who are employees.

PMID- 16418045
TI  - Anthropometry of 5-19-year-old Tongan children with special interest in the high
      prevalence of obesity among adolescent girls.
AB  - BACKGROUND: Despite much concern about adult obesity among Pacific Islanders,
      childhood obesity has seldom been investigated. AIM: Based on the anthropometry
      of Tongan children aged 5-19 years, this study aims to elucidate age and sex
      differences in obesity prevalence calculated from BMI and its relation to body
      fat estimated by skinfold thicknesses. SUBJECTS AND METHODS: 895 students, aged 5
      19 years, in the most modernized island and a remote island, were measured for
      stature, body weight, circumferences at waist, hip and mid-upper arm, and
      skinfold thicknesses at biceps, triceps and subscapular. The prevalence of
      overweight and obesity was calculated using the reference data of the
      International Obesity Task Force (IOTF) and the Centers for Disease Control and
      Prevention (CDC). RESULTS: The prevalence of obesity of Tongan adolescent girls
      defined by the IOTF and CDC references was 19.4% and 22.8%, respectively, being
      considerably higher than that of not only juvenile girls but also adolescent
      boys. Among adolescents, the girls' BMI was positively correlated with fat mass
      whereas in boys it was not. The sex difference in adolescents was parallel to
      that in adults, being attributable to gender differences in daily behavioural
      patterns. CONCLUSIONS: Among Tongan adolescents, obesity prevalence in girls was
      much higher than in boys, in association with fat accumulation in the former.

PMID- 16418046
TI  - Genetic structure and admixture in urban populations of the Argentine North-West.
AB  - BACKGROUND: From the ethnic point of view, the Argentine North-West (ANW)
      constitutes one of the most noticeable areas in the country due to the cultural
      peculiarities that integrate it to the Andean world and the ethno-historical and
      demographic characteristics of how it became populated. AIM: The study analysed
      the genetic structure and diversity of the ANW urban populations, and the
      contribution of parental populations to its genetic pool. SUBJECTS AND METHODS:
      Previously reported data on allele frequencies of HLA-A and HLA-B loci of 1293
      individuals from Jujuy, Salta, Tucuman, Santiago del Estero, Catamarca and La
      Rioja were used. Our estimates include: (a) genetic intra-population diversity;
      (b) genetic distances between populations; (c) linkage disequilibrium (LD); (d)
      admixture rates and genetic distances with respect to three parental populations
      (European, American Indian and African). RESULTS: Low intra-population genetic
      differentiation and low genetic distances between populations were found.
      Differential LD distribution varied according to province, with 60% variance due
      to intra-population differences. The Spanish contribution (50%) predominated in
      ANW, followed by the American Indian (40%) and African (10%) contributions, and a
      marked inter-population heterogeneity of genetic admixture rates was observed.
      The shortest genetic distance was found in the American Indian parental
      population, and the longest in the African parental population. CONCLUSION: Five
      hundred years after the Spanish conquest, urban populations at ANW that have
      probably been subject to the same evolutionary forces present low genetic
      diversity and a similar genetic structure. Genetic distances and admixture
      percentages observed agree with census and ethno-historical data on settlement in
      the region.

PMID- 16418047
TI  - Beta-blockers reduce bone resorption marker in early postmenopausal women.
AB  - BACKGROUND: There is evidence to suggest that beta-blockers used in the
      management of cardiovascular disease may also modulate bone metabolism and reduce
      bone fragility. AIM: The study aimed to determine the association between beta
      blocker use, serum markers of bone turnover and bone loss in early postmenopausal
      women. SUBJECTS AND METHODS: In this observational study, we evaluated beta
      blocker exposure in association with serum levels of C-telopeptide and bone
      specific alkaline phosphatase, and rates of bone loss. Beta-blocker use,
      concomitant therapy and lifestyle were documented for 197 women (50-59 years),
      175 of whom had changes in whole body bone mineral density monitored over a 2
      year period. RESULTS: Twenty-four beta-blocker users were identified at baseline.
      After controlling for concomitant use of hormone therapy, C-telopeptide levels
      were 6.7% lower among beta-blocker users (p=0.02). No association was detected
      between bone-specific alkaline phosphatase and beta-blocker use. Analysis of 15
      beta-blocker users and 152 non-users identified 2 years post-baseline showed that
      levels of C-telopeptide but not bone-specific alkaline phosphatase were
      predictors of adjusted rates of bone loss (p=0.008 and p>0.05, respectively).
      Adjusted rates of bone loss were-0.001+/-0.026 g cm(-2) over 2 years for the
      users and-0.004+/-0.025 g cm(-2) over 2 years for non-users, but this difference
      was not significant. CONCLUSION: Beta-blockers might suppress bone resorption
      with relative preservation of bone formation. A study with greater power is
      required to determine whether ss-blocker use is associated with lower rates of
      bone loss.

PMID- 16418048
TI  - Short-term pharmacologically induced growth study of ontogenetic allometry of
      oxygen uptake in children.
AB  - BACKGROUND: A range of allometric coefficients have been proposed in describing
      the maximal oxygen uptake (VO2max): body mass relation in children using weight
      bearing ergometry. However, a wide deviation in the allometric coefficients for
      VO2max may be apparent when selected pediatric cohorts are studied in conjunction
      with clinical intervention for growth abnormalities. AIM: The purpose of this
      study was to determine the allometric coefficients for VO2max after short-term
      pharmacologically induced growth in pre- and early pubescent children. SUBJECTS
      AND METHODS: The treatment group consisted of nine subjects with non-growth
      hormone (GH)-deficient short stature and one with GH-deficient short stature
      (mean age: 13.7+/-1.7 years). Ten pre- and early pubescent children matched for
      age, height, weight, VO2max and body mass index (BMI) were controls. The
      treatment group were evaluated before (Pre-GH) and after (Post-GH) 4 months of
      subcutaneous GH therapy (0.05 mgkg(-1)day(-1) x 6 days week(-1)). RESULTS: The
      mean ontogenetic coefficient for the treatment group was 1.50+/-0.20 and for the
      control group was 0.77+/-0.34. The mean allometric coefficient for body mass
      relative to VO2max was significantly higher in the treatment group compared with
      the control group (p<0.05). Height, weight, fat free mass (FFM), VO2max indexed
      to body mass (mLkg(-1)min(-1)) and FFM (mLkgFFM(-1)min(-1)) increased (p<0.05)
      with GH therapy. GH therapy also increased insulin-like growth factor-I (IGF-I)
      and served as a biochemical marker of GH therapy (p<0.05). The control group had
      no significant differences in all the variables tested (p<0.05). CONCLUSION: The
      scaling for oxygen uptake (VO2) for body mass varies with GH treatment and the
      increase in VO2max that commonly occurs in conjunction with physical growth in
      the pre-and early pubescent individual may be linked to an increase in FFM and
      linear size.

PMID- 16418049
TI  - Changes in metacarpal bone mineral density with age and menopause using computed
      X-ray densitometry in Japanese women: cross-sectional and longitudinal study.
AB  - BACKGROUND: Bone mineral density (BMD) loss with age and menopause is widely
      accepted in elderly women. However, only a few studies have utilized a multiple
      regression model that includes physical characteristics to assess comprehensive
      lifetime changes in BMD. OBJECTIVE: A prospective study was conducted to
      characterize the normal patterns in metacarpal BMD changes in Japanese women, and
      to assess the applicability of a fitting model using cross-sectional data
      compared with longitudinal variability. SUBJECTS AND METHODS: The study consisted
      of 5422 healthy women in cross-sectional data and a 1-year follow-up of 359
      women. The metacarpal BMD was measured by computed X-ray densitometry. Multiple
      linear and nonlinear regression analyses were performed in cross-sectional
      subjects. Nonparametric analysis was used to compare percentage rates of BMD
      changes between actual and estimated values. RESULTS: The cross-sectional data
      showed that the best-fit equation was a nonlinear change model using the
      variables of age and height in premenopausal women, and years since menopause
      (YSM), age and height in postmenopausal women. The results of longitudinal data
      indicated the following. In premenopausal women, the actual BMD changes were
      greater in the 30-39 age group than the 20-29 age group and were less in the 50
      59 group than the 40-49 group. The rates of annual change in BMD between the
      actual value and estimated value by change model were very similar. In
      postmenopausal women, the actual changes in BMD indicated that the rapid rate of
      reduction observed was over 3% at 0-5 YSM and 1.5% at 6-10 YSM, and thereafter
      showed a slower rate of decline at 11 YSM. The change model represented the trend
      of actual change in BMD for postmenopausal women, whereas the rates of estimated
      BMD loss underestimated the actual changes at 1-10 YSM. CONCLUSION: The change
      model for premenopausal women using cross-sectional data is beneficial in
      evaluating the actual metacarpal BMD variability, whereas that for postmenopausal
      women is insufficient in estimating the longitudinal BMD variability.

PMID- 16418050
TI  - Predictive equations for stature in the elderly: a study in three Latin American
      cities.
AB  - AIM: The aim of this study was to develop predictive equations based on
      anthropometric data to estimate stature in people 60 years and older in Latin
      America. DESIGN: Population-based cross-sectional study in three Latin American
      cities. SUBJECTS: Sample sizes were n=1657 (Sao Paulo, Brazil), n=1004 (Santiago,
      Chile) and n=995 (Mexico City, Mexico). METHOD: The prediction equations were
      fitted by stepwise linear regression analysis. For each country and sex, samples
      were randomly split into two sub-samples (training and validation sub-samples)
      using the cross-validation method. RESULTS: Stepwise regression analysis in the
      training sample revealed that only knee-height and age had a significant effect
      on the prediction of height. The values of the shrinkage statistic were below 0.1
      indicating the reliability of the prediction equations. The regression equations
      had standard errors of estimate ranging from 3.3 cm (Chile), 3.6 cm (Brazil) and
      4.0 cm (Mexico) for women, and 3.7 cm (Mexico and Chile) and 3.8 cm (Brazil) for
      men. CONCLUSIONS: Sex-specific stature prediction equations based on knee-height
      and age were obtained from large representative samples from selected cities of
      Latin America.

PMID- 16418051
TI  - High specificity of head circumference to recognize N540K mutation in
      hypochondroplasia.
AB  - Hypochondroplasia (HCH) is a skeletal dysplasia characterized by short stature
      with disproportionately short arms and legs. Anthopometrics and skeletal features
      are very similar to achondroplasia but milder. Seventy per cent of affected
      individuals are heterozygous for a mutation of the FGFR3 gene. Differences in
      some anthropometric measurements in affected patients with and without N540K
      mutation were analysed. Diagnosis of the disease was made on the presence of
      previously standardized criteria: short stature, short limbs and three or more X
      ray features. Genomic DNA was extracted from peripheral blood leukocytes by
      standard procedures. PCR amplification of exons 10, 13 and 15 of FGFR3 was
      performed. Twenty-six patients were studied (median age was 7.31, range 0.27-20.0
      years). Sitting height, body proportions and head circumference (HC) were
      statistically different in the mutated group. Receiver Operating Characteristic
      (ROC) analysis was carried out in order to estimate the discriminating power of
      different cut-off points of HC for recognizing patients with and without the
      mutation. A figure of 1.86 SD for HC was found to have a sensitivity of 73.3% and
      specificity of 100% for detecting HCH patients with the mutation. All of them had
      a HC greater than 1.86?SD. These results contribute to a better characterization
      of the clinical-molecular relationships in HCH.

PMID- 16418054
TI  - The cognitive competence of speakers with acquired dysarthria: judgements by
      doctors and speech and language therapists.
AB  - BACKGROUND: Studies have shown that listeners make negative attributions towards
      people with communication impairments. This appears to be the case for health
      care professionals as well as non-professional listeners. AIMS: This study
      extends this line of research to speakers with acquired dysarthria. These clients
      often complain that listeners treat them differently after the onset of their
      speech impairment. The study examines judgements of the cognitive status of
      speakers with acquired dysarthria made by health care professionals. METHODS AND
      PROCEDURES: Doctors, speech and language therapists and speech and language
      therapy students viewed videos of speakers with acquired dysarthria and of
      controls matched for age and gender who had acquired neurological deficits that
      did not affect their speech. Listeners judged whether speakers could carry out a
      number of everyday tasks. All the tasks were known to be within the speakers'
      competence. OUTCOMES AND RESULTS: Doctors were significantly less confident of
      the competence of speakers with dysarthria than of the controls. No difference
      was found for speech and language therapists or speech and language therapy
      students. CONCLUSIONS: Although caution is required in generalizing these results
      to other speakers, the results lend some support to the complaints of clients
      with acquired dysarthria that their speech leads others, in this case doctors, to
      misjudge their cognitive competence.

PMID- 16418055
TI  - Alzheimer's disease-associated disability: an ICF approach.
AB  - PURPOSE: The aim of the study is to provide a description of dementia-associated
      disability in Alzheimer's disease (AD) patients through the International
      Classification of Functioning, Disability and Health (ICF). METHOD: Twenty-six AD
      patients at different stages of disease participated in the study. Mini Mental
      State Examination (MMSE) and Global Deterioration Scale (GDS) were used to stage
      the degree of cognitive impairment and the stage of disease, respectively. All
      subjects were classified using the ICF categories in the more detailed four-level
      version. Correlation between compromised ICF items and both MMSE and GDS scores
      were calculated through Spearman Rho test. RESULTS: Mental functions were
      impaired in all the subjects examined. Data on activity and participation showed
      that not only domestic life, self care, and mobility but also communication and
      interaction and social relationships are compromised in AD patients. Three main
      areas appeared as the most relevant facilitators: products and technology,
      support and relationship and services, systems and policies. ICF codes were
      generally correlated with both MMSE and GDS: subjects who appeared more
      compromised on MMSE and GDS showed higher impairment of functions, activity
      limitation, and participation restriction.Conclusion. ICF is a useful tool to
      describe health status in AD patients in that it underlines important aspects of
      daily living generally not considered by activity of daily living scales such as
      communication, social relationships, and recreation and leisure.

PMID- 16418056
TI  - Standard of living in the retirement survey: a predictor of six-year functional
      limitation onset and mortality in women, but not in men from ages 55 - 69 years.
AB  - PURPOSE: To investigate the predictive validity for health decline of a standard
      of living, a measure that combines basic necessities and consumer durables.
      METHOD: A nationally representative sample of those aged 55-69 years was
      interviewed at home in the Great Britain Retirement and Retirement Plans Survey,
      (1988; n=3,541). In 1994, 2,247 were re-interviewed, response rate being 70% of
      survivors. Relationships between socioeconomic status and health decline were
      investigated using polytomous logistic regression modelling. The outcomes were
      onset of functional limitation and mortality. RESULTS: Standard of living was an
      independent predictor of 6-year functional limitation onset (Odds Ratio compared
      to good standard of living 2.2; 95% Confidence Interval 1.3-3.8) and mortality
      (OR=4.6; 95% CI 2.3-8.9) in women, with age, household type, educational
      qualifications and social class taken into account. However, in men, weaker
      associations were largely accounted for by differences in education and social
      class (adjusted OR for functional limitation onset 1.0; 95% CI 0.5-1.9; adjusted
      OR for mortality 1.4; 95% CI 0.6-2.9). A combined indicator of housing tenure and
      property value was also an independent predictor of functional limitation onset
      in women. CONCLUSIONS: Poor standard of living identifies women but not men at
      risk of health decline who are missed by social class and educational level.
      Measures of current home-based material resources are a useful addition to
      minimum datasets for monitoring health inequalities.

PMID- 16418057
TI  - The Orpington Prognostic Scale for patients with stroke: reliability and pilot
      predictive data for discharge destination and therapeutic services.
AB  - PURPOSE: To determine the inter-rater and test-retest reliability of the
      Orpington Prognostic Scale (OPS) in patients with stroke. Pilot data were
      gathered to evaluate its predictive validity for discharge destination and
      therapeutic services required on discharge. METHOD: Ninety-four consecutive
      patients, admitted to hospital due to stroke participated. Pairs of
      physiotherapists (PT) and occupational therapists (OT) assessed patients using
      the OPS on days 7 and 14 post stroke. For inter-rater reliability, one rater
      performed the OPS while the other observed, each scoring the scale independently.
      For test-retest reliability, two different raters tested the subjects separately
      within the same day. Data were gathered on the discharge destination and the
      number of follow-up services prescribed. RESULTS: The inter-rater reliability as
      measured by the intraclass correlation coefficient (ICC) was 0.99 (95% CI 0.97 -
      0.99). For test-retest reliability, the ICC was 0.95 (95% CI 0.90 - 0.98). The
      accuracy for predicting discharge to home using OPS 5.0 was 65% (95% CI 0.52 -
      0.76). OPS scores were not related to number of follow-up services prescribed.
      CONCLUSIONS: Despite high inter-rater and test-retest reliability, the OPS has
      limited predictive accuracy for discharge destination and is a poor predictor of
      follow-up services.

PMID- 16418058
TI  - A pilot study of a web-based physical activity motivational program for adults
      with physical disabilities.
AB  - PURPOSE: Develop, deliver, and assess the efficacy of a 4-week web-based leisure
      time physical activity (LTPA) motivational program based on the Transtheoretical
      Model and tailored to inactive adults with physical disabilities. METHOD: This
      was a pilot-based study incorporating a true experimental design with one
      treatment and one control group. The intervention program was delivered on the
      web and was based on the constructs of the Transtheoretical Model. From the 151
      individuals who completed the LTPA standardized questionnaire at baseline, 75
      people participated in the 1-month post-test assessment. RESULTS: The results of
      the analysis confirmed the pretest LTPA scores as the study covariate for the
      post-test assessment (F (1,72)=16.06, p=0.001, (2 )= 0.18). Based on the one-way
      ANCOVA, there were no statistically significant differences in LTPA scores
      between the treatment and control groups at post-test. However, the corresponding
      effect size and variance explained by the treatment approached a moderate level
      of significance (d=0.34 and (2 )= 0.04). CONCLUSIONS: Although conclusive
      statements about program effectiveness cannot be secured, several 'lessons
      learned' from this project may be 'key factors' for program improvement. Given
      the pilot nature of the study and the limited resources for program development
      and monitoring, continued examination of such motivational materials and delivery
      mechanisms for people with physical disabilities appear warranted.

PMID- 16418059
TI  - Vibration exposure of individuals using wheelchairs over sidewalk surfaces.
AB  - According to the International Standards Organization 2631-1 standard on human
      vibration, individuals in a seated position are at risk of injury due to whole
      body vibrations when exposed for long periods of time. Wheelchair users fit this
      description perfectly; however, little research has been conducted to evaluate
      the amount of vibration transmitted to a wheelchair user. The vibration exposure
      produced by traversing nine surfaces was evaluated by having 10 individuals
      without disabilities propel over them in both a manual wheelchair at 1 m/s and a
      powered wheelchair at 1 and 2 m/s. Root-mean squared (RMS) vertical vibration was
      examined to determine if differences existed between surfaces. At 1 m/s for both
      the manual and the powered wheelchair the 8-mm bevel interlocking concrete
      surface produced significantly higher RMS vertical vibration than the other
      surfaces. At 2 m/s in the powered wheelchair, the poured concrete surface
      (control) produced the significantly highest RMS vertical vibration. Based on the
      manual and power wheelchair results of this study, use of selected ICPI pavers
      would be acceptable for any route traveled by individuals using wheelchair.
      Furthermore, a 90 degrees herringbone pattern is preferred over the 45 degrees
      pattern, and it is recommended that for safety reasons regarding vibration
      exposure a bevel of less than 6 mm should be used.

PMID- 16418060
TI  - Vision needs of people with intellectual disability in residential facilities and
      community-based homes for independent living.
AB  - PURPOSE: The purpose of this study is to assess the visual problems of people
      with intellectual disability in residential and community-based facilities.
      METHOD: A purposive sample of 146 male and female adults, aged 21 and older,
      living in residential facilities and community-based homes in the southern region
      of Israel was used to assess and compare vision problems. RESULTS: Among those
      screened, 77% were found to have a visual problem. Only astigmatism was found to
      differentiate the two groups. Those living in the community, particularly men,
      were more likely to have astigmatism. CONCLUSIONS: Addressing the eye care needs
      of people with intellectual disability is a difficult process. People with
      intellectual disability, however, need ophthalmological and optometric screening
      to determine whether they can benefit from such intervention, including cataract
      removal and eyeglasses, to improve their quality of life.

PMID- 16418062
TI  - Kinetic modelling of passive transport and active efflux of a fluoroquinolone
      across Caco-2 cells using a compartmental approach in NONMEM.
AB  - The purpose was to develop a general mathematical model for estimating passive
      permeability and efflux transport parameters from in vitro cell culture
      experiments. The procedure is applicable for linear and non-linear transport of
      drug with time, <10 or >10% of drug transport, negligible or relevant back flow,
      and would allow the adequate correction in the case of relevant mass balance
      problems. A compartmental kinetic approach was used and the transport barriers
      were described quantitatively in terms of apical and basolateral clearances. The
      method can be applied when sink conditions are not achieved and it allows the
      evaluation of the location of the transporter and its binding site. In this work
      it was possible to demonstrate, from a functional point of view, the higher
      efflux capacity of the TC7 clone and to identify the apical membrane as the main
      resistance for the xenobiotic transport. This methodology can be extremely useful
      as a complementary tool for molecular biology approaches in order to establish
      meaningful hypotheses about transport mechanisms.

PMID- 16418063
TI  - Styrene monomer primarily induces CYP2B1 mRNA in rat liver.
AB  - To determine the cytochrome P450 (CYP) primarily expressed after styrene
      exposure, seven forms of hepatic CYP mRNA in rats treated with 600 mg kg(-1)
      styrene were examined. CYP1A2, CYP2B1/2, CYP2E1 and CYP3A2 mRNA were observed
      using real-time LightCycler PCR. The amount of CYP2B1 mRNA was significantly
      increased, 47-fold compared with controls, suggesting that this CYP is the
      primary cytochrome P450 in rats exposed to styrene. Significant increases in the
      amount of CYP2E1, CYP1A2 and CYP2B2 mRNA were also observed after styrene
      exposure, and their increase levels were 3.1-, 1.7- and 1.7-fold higher than
      controls, respectively. Western blot analysis also indicated that the protein
      levels of CYP2B1, CYP2B2, CYP2E1 and CYP1A2 showed clear increases after styrene
      treatment, corresponding to their mRNA expression. CYP2C11 mRNA decreased
      significantly in rats after styrene exposure. CYP1A1 was detected at the mRNA
      level in rat liver, but it was not detected at the protein level. The expression
      of epoxide hydrolase (EH), involved in Phase I drug metabolism, was also
      examined. EH mRNA increased 2-fold compared with controls after styrene exposure.
      Styrene thus appears to be a chemical compound that induces multiple CYPs. The
      results demonstrate that CYP2B1 is the primarily induced CYP form by styrene
      treatment to rats at acute toxic level.

PMID- 16418064
TI  - Sulfation of resveratrol in human liver: evidence of a major role for the
      sulfotransferases SULT1A1 and SULT1E1.
AB  - Sulfation of resveratrol, a polyphenolic compound present in grapes and wine with
      anticancer and cardioprotective activities, was studied in human liver cytosol.
      In the presence of 3'-phosphoadenosine-5'-phosphosulfate, three metabolites (M1
      3) whose structures were identified by mass spectrometry and NMR as trans
      resveratrol-3-O-sulfate, trans-resveratrol-4'-O-sulfate, and trans-resveratrol-3
      O-4'-O-disulfate, respectively. The kinetics of M1 formation in human liver
      cytosol exhibited an pattern of substrate inhibition with a K(i) of 21.3 +/- 8.73
      microM and a V(max)/K(m) of 1.63 +/- 0.41 microLmin(-1)mg(-1) protein. Formation
      of M2 and M3 showed sigmoidal kinetics with about 56-fold higher V(max)/K(m)
      values for M3 than for M2 (2.23 +/- 0.14 and 0.04 +/- 0.01 microLmin(-1)mg(-1)).
      Incubation in the presence of human recombinant sulfotransferases (SULTs)
      demonstrated that M1 is almost exclusively catalysed by SULT1A1 and only to a
      minor extent by SULT 1A2, 1A3 and 1E1, whereas M2 is selectively formed by
      SULT1A2. M3 is mainly catalysed by SULT1A2 and 1A3. In conclusion, the results
      elucidate the enzymatic pathways of resveratrol in human liver, which must be
      considered in humans following oral uptake of dietary resveratrol.

PMID- 16418065
TI  - Characterization of the enzymes involved in the in vitro metabolism of amrubicin
      hydrochloride.
AB  - The in vitro metabolism of amrubicin by rat and human liver microsomes and
      cytosol was examined. The main metabolic routes in both species were reductive
      deglycosylation and carbonyl group reduction in the side-chain. In vitro
      metabolism of amrubicinol by rat and human liver microsomes and cytosol was also
      examined and the main metabolic route of this active metabolite was reductive
      deglycosylation. Metabolism of amrubicin in human liver microsomes was inhibited
      by TlCl(3) and that in human liver cytosol was inhibited by dicumarol and
      quercetin. Generation of amrubicinol was inhibited only by quercetin. The results
      indicate that metabolism of amrubicin is mediated by NADPH-cytochrome P450
      reductase, NADPH:quinone oxidoreductase and carbonyl reductase. In addition,
      generation of amrubicinol is mediated by carbonyl reductase. Metabolism of
      amrubicinol in human liver microsomes was inhibited by TlCl(3) and that in human
      liver cytosol was inhibited by dicumarol. The results indicate that metabolism of
      amrubicinol is mediated by NADPH-cytochrome P450 reductase and NADPH:quinone
      oxidoreductase. To investigate the influence of cisplatin on the metabolism of
      amrubicin and amrubicinol, human liver microsomes and cytosol were pre-incubated
      with cisplatin. This did not change the rates of amrubicin and amrubicinol
      metabolism in either human liver microsomes or cytosol.

PMID- 16418066
TI  - Characterization of the Phase II metabolites of rutaecarpine in rat by liquid
      chromatography-electrospray ionization-tandem mass spectrometry.
AB  - From the authors' previous studies on the Phase I metabolism of rutaecarpine,
      nine metabolites formed were identified as products of hydroxylation on the
      aromatic rings in rat liver microsomes. In order to determine the possible
      metabolic fate of rutaecarpine, the Phase II metabolites of rutaecarpine were
      characterized in the present study by using liquid chromatography/electrospray
      ionization-tandem mass spectrometry (LC/ESI-MS). When male Sprague-Dawley rats
      were treated intravenously with 4 mg kg(-1) rutaecarpine, 16 different Phase I
      and II metabolites were identified in urine including four sulfate and four
      glucuronide conjugates. Phase I metabolites of rutaecarpine were identified as
      four mono-hydroxylated metabolites (M2-5) and four isobaric di-hydroxylated
      metabolites (M6-9). These metabolites were identical to the in vitro metabolites
      except one, which was hydroxylated in the aliphatic moiety. In addition, Phase II
      metabolites were identified as conjugated with sulfate (S1-4) and glucuronide (G1
      4). In faeces, 11 different metabolites were identified. The metabolites M8 and
      glucuronide conjugated (G1-4) were not detected. Structures of all metabolites
      were confirmed with CID fragmentation spectra of MS(2), MS(3) and retention times
      by LC/ESI-MS.

PMID- 16418067
TI  - Reaction of nitroso derivatives of dinitropyrenes with sulfhydryl groups of
      peptides and hemoglobin in vitro and in rats.
AB  - Diesel engine emissions have been classified as a potential human carcinogen and
      may cause a variety of other health effects. Human exposure to diesel engine
      emissions is highly variable within the population. Therefore, specific methods
      for the biomonitoring of human exposure to diesel engine emissions are required
      for exposure assessment within epidemiological studies. Haemoglobin adducts of
      dinitropyrenes may serve as biomarkers for human exposures to diesel engine
      emissions.To characterize structures of dinitropyrene reaction products with
      sulfhydryl groups, glutathione was used to trap electrophilic nitroso
      intermediates formed from dinitropyrenes and glutathione S-conjugates were
      identified and characterized by Qtrap techniques using (HPLC-MS/MS) high
      performance liquid chromatography coupled to triple quadrupole mass spectrometry.
      Nitrosonitropyrene-derived sulfinamides, sulfenamides and glutathione thioethers
      bound to carbon atoms in the aromatic ring, presumably formed by a rearrangement
      of intermediate sulfenamide cations, were formed in low yields. In haemoglobin
      from rats orally administered dinitropyrenes, mild alkaline hydrolysis of
      haemoglobin released aminonitropyrenes, which were identified by HPLC-MS/MS. The
      results demonstrate that dinitropyrenes undergo nitroreduction in rats and that
      the intermediate nitrosonitropyrenes bind to heamoglobin. The haemoglobin adducts
      formed from dinitropyrenes seem, in contrast to previous studies, to be
      hydrolysable and thus represent sulfen- and sulfinamides derived from the
      intermediate nitrosonitropyrenes. The developed Qtrap methods to detect and
      characterize glutathione S-conjugates rapidly may have wide applications in
      attempts to characterize reactive intermediates formed in complex mixtures in low
      concentrations.

PMID- 16418068
TI  - Special respect redux.

PMID- 16418069
TI  - On the nature and purpose of public discourse.

PMID- 16418070
TI  - Extracorporeal embryos and three conceptions of the human.

PMID- 16418071
TI  - How not to argue that embryos lack full moral status.

PMID- 16418074
TI  - Recapturing the essence of spirituality: a letter to the guest editor.

PMID- 16418075
TI  - Spiritual well-being, sleep disturbance, and mental and physical health status in
      HIV-infected individuals.
AB  - A growing body of evidence demonstrates a significant relationship between
      spirituality and health. HIV-infected individuals often find new meaning and
      purpose for their lives while establishing new connections and strengthening old
      ones. This descriptive, correlational study examined the relationships among
      spiritual well-being, sleep quality, and health status in 107 HIV-infected men
      and women. Spiritual well-being was found to be a significant factor related to
      both sleep quality and mental and physical health status. Every study participant
      reported sleep disturbance. The findings suggest that spiritual well-being and
      sleep quality need to be assessed so appropriate interventions can be implemented
      to improve health outcomes in this population.

PMID- 16418076
TI  - Religion, relationships and mental health in midlife women following acute
      myocardial infarction.
AB  - Little is known about coping in women following an acute myocardial infarction
      (AMI). In midlife, women have worse outcomes than men following AMI. Innovative
      interventions need to be developed that respond to these women's unique recovery
      needs. In this correlational, descriptive study, 59 women aged 35-64 who had
      experienced AMI reported low satisfaction with life and decreased mental health;
      49% were experiencing depression. However, they also reported that religion,
      family, and friends provided strength and comfort at the time of their AMI.
      Greater activation of simple, family-oriented, coping resources during recovery
      may be key. It is recommended that mental health nurses be essential members of
      the recovery planning team.

PMID- 16418077
TI  - A systematic review of recent research on adolescent religiosity/spirituality and
      mental health.
AB  - There is accumulating evidence that religiosity/spirituality (R/S) are important
      correlates of mental health in adult populations. However, the associations
      between R/S and mental heath in adolescent populations have not been
      systematically studied. The purpose of this article is to report on a systematic
      review of recent research on the relationships between adolescent R/S and mental
      health. Twenty articles between 1998 and 2004 were reviewed. Most studies (90%)
      showed that higher levels of R/S were associated with better mental health in
      adolescents. Institutional and existential dimensions of R/S had the most robust
      relationships with mental health. The relationships between R/S and mental health
      were generally stronger or more unique for males and older adolescents than for
      females and younger adolescents. Recommendations for future research and
      implications for mental health nursing are discussed.

PMID- 16418078
TI  - Spirituality, mental health, physical health, and health-related quality of life
      among women with HIV/AIDS: integrating spirituality into mental health care.
AB  - HIV-positive women have used spirituality as a resource to enhance their
      psychological well-being and health-related quality of life (HRQOL). The purpose
      of this article is to review the literature about depression among HIV-positive
      women and to describe the positive associations reported among spirituality,
      mental health, and HRQOL. This article also advocates the development and use of
      interventions integrated with spirituality. The incorporation of spirituality
      into traditional mental health practices can optimize healthcare for HIV-positive
      women who are diagnosed with depression. A case example is presented and
      spiritual implications are discussed.

PMID- 16418079
TI  - Religious activities and health outcomes: the College Bound Sisters Program.
AB  - College Bound Sisters (CBS) is a program that helps younger sisters of teenage
      mothers change their life trajectory by accomplishing three objectives: avoidance
      of pregnancy, completion of high school, and enrollment in college. Data related
      to religious activities and accomplishment of the three objectives for 129
      members were analyzed using chi square. CBS defines health as the accomplishment
      of the three program objectives using Norbeck's theoretical model of social
      support. The adolescents were divided into three groups: those who became
      pregnant, dropped out of school, or completed high school. The three groups were
      compared with regard to the frequency of participating in religious activities.
      The majority of the CBS adolescents reported participating in weekly religious
      activities. No significant difference was found among the three groups, with
      regard to religious activities. However, CBS program participants were more
      likely than nonparticipants to graduate high school and enroll in college.
      Implications for incorporating religious activities in teenage pregnancy
      prevention programs are discussed.

PMID- 16418080
TI  - Spiritual experiences of parents and caregivers who have children with
      disabilities or special needs.
AB  - Despite the fact that faith has been described as a universal concern, and
      despite the realization that the presence of social supports is an essential
      element in successful coping, there has been no systematic examination of the
      quality of spiritual networks important to families impacted by childhood
      disability. There is also little understanding of how spirituality in children
      influences the lived experience of faith in the adults who care for them.
      Findings reported here come out of a larger existential phenomenology study that
      examined the lived experience of parents or caregivers who sought to obtain
      formal religious education for their children with special needs. Participants
      included 26 parents/caregivers representing 44 children with special needs and 15
      different faith traditions. Narratives indicated that many clergy and members of
      faith communities either devalue or fail to recognize the spiritual lives of
      disabled children. This lack of recognition was associated with participant
      disillusionment or crises of faith and a sense of alienation from potential
      sources of emotional support. In contrast, those participants whose children were
      welcomed reported feeling sustaining support and strengthened faith. No parent or
      caregiver perceived nurses as having an awareness of or interest in spirituality
      within families of children who have special needs.

PMID- 16418081
TI  - Maximum sustainable work rate for five protective clothing ensembles with respect
      to moisture vapor transmission rate and air permeability.
AB  - The fabrics associated with protective clothing affect heat stress, which
      influences productivity and risks of heat-related disorders. This study compared
      the work limiting effects of five protective coveralls and a semiclothed
      condition (t-shirt and shorts). Two fabric characteristics determined from bench
      tests, moisture vapor transmission rate (MVTR), and air permeability were also
      examined as possible predictors of ensemble performance. A progressive metabolic
      rate protocol was used where environmentalconditions (T(db) = 32 degrees C;
      T(pwb) = 26 degrees C) were held constant while treadmill speed was slowly
      increased. The limiting metabolic rate to just maintain thermal equilibrium was
      the critical point. At this point, critical speed and critical metabolic rate
      were noted and total evaporative resistance was calculated for each ensemble.
      Five acclimatized subjects wore each of the six clothing conditions in a random
      order. Statistically significant differences were found among the five protective
      garments and a semiclothed ensemble for critical treadmill speed (S(crit)),
      critical metabolic rate (M(crit)), and total evaporative resistance (R(e-t)). The
      semiclothed condition (S(crit) = 1.77 m/sec; M(crit) = 580 W; R(e-t) = 0.0099 kPa
      m2/W) and ensembles made from spunbonded, melt blown, spunbonded polypropylene
      (SMS) (1.72 m/sec; 560 W; 0.0135 kPa m2/W) and spunbonded polypropylene (1.67
      m/sec; 550 W; 0.0126 kPa m2/W) were able to support higher work rates than
      fabrics made from Tyvek 1422-A (a nonwoven spunbonded olefin) (1.48 m/sec; 470 W;
      0.0183 kPa m2/W) and a microporous film supported by spunbonded polypropylene
      (1.34 m/sec; 420 W; 0.0231 kPa m2/W). A tightly woven polyester ensemble (1.59
      m/sec; 510 W; 0.0130 kPa m2/W) had intermediate values and was not significantly
      different from either group. Air permeability was a better predictor of fabric
      work limiting performance than MVTR. An air permeability on the order of 10,000
      L/min cm2 bar would have little effect on maximum sustainable work.

PMID- 16418082
TI  - An exposure study of bystanders and workers during the installation and removal
      of asbestos gaskets and packing.
AB  - From 1982 until 1991, a series of studies was performed to evaluate the airborne
      concentration of chrysotile asbestos associated with replacing gaskets and
      packing materials. These studies were conducted by the senior author in response
      to concerns raised by a report from the Navy in 1978 on asbestos exposures
      associated with gasket work. A series of studies was conducted because results of
      those who worked with gaskets within the Navy study did not address the
      background concentrations of asbestos in the work areas, which may have been
      significant due to the presence of asbestos insulation in the ships and
      shipyards. The intent of the studies performed from 1982 through 1991 was to re
      create the Navy's work practices in a contaminant-free environment during an 8
      hour workday (so the data could be compared with the OSHA permissible exposure
      limit [PEL]). Samples were collected to characterize personal and area airborne
      asbestos concentrations associated with the formation, removal, and storage of
      gaskets, as well as the scraping of flanges and the replacement of valve packing.
      The results indicate that the 8-hour time-weighted average (TWA) exposures of
      pipefitters and other tradesmen who performed these activities were below the
      current PEL and all previous PELs. Specifically, the highest average 8-hour TWA
      concentration measured for workers manipulating asbestos gaskets during this
      study was 0.030 f/cc (during gasket removal and flange face scraping onboard a
      naval ship). Likewise, the 8-hour TWA breathing zone concentrations of a worker
      removing and replacing asbestos valve packing did not exceed 0.016 f/cc. In most
      cases, the concentrations were not distinguishable from ambient levels of
      asbestos in the ships or the general environment. These results are not
      surprising given that asbestos fibers in gasket materials are encapsulated within
      a binder.

PMID- 16418083
TI  - An application of exposure modeling in exposure assessments for a university
      chemistry teaching laboratory.
AB  - Chemical exposures in a university teaching lab were assessed using a tiered
      approach to modeling. Zero ventilation and well mixed room models estimated air
      concentrations of ethyl ether, n-hexane, and methylene chloride during
      distillation and extraction exercises. A simple, zero ventilation model
      determined that health risks from the ethyl ether exercise were minimum. N-hexane
      and methylene chloride exposures were evaluated with higher tiered, well mixed
      room models. An assumption that all of the solvent evaporated during the lab
      resulted in estimated n-hexane concentrations well below the occupational
      exposure limit. Methylene chloride concentration estimates using this approach
      were only one-half the occupational exposure limit, so the model was refined
      using information on the actual amount of solvent that evaporated. This resulted
      in a concentration estimate approximately one-fifth of the occupational exposure
      limit. Air sampling was done to evaluate model performance. Measured
      concentrations were higher than modeled concentrations by up to a factor of two
      but were still below applicable occupational exposure limits. The exposure models
      selected were deemed useful in the assessment of exposure acceptability in these
      labs.

PMID- 16418084
TI  - Safety and effectiveness of fentanyl administration for prehospital pain
      management.
AB  - OBJECTIVE: To determine the safety and effectiveness of fentanyl administration
      for prehospital pain management. METHODS: This was a retrospective chart review
      of patients transported by ambulance during 2002-2003 who were administered
      fentanyl citrate in an out-of-hospital setting. Pre- and post-pain-management
      data were abstracted, including vital signs, verbal numeric pain scale scores,
      medications administered, and recovery interventions. In addition, the emergency
      department (ED) charts of a subgroup of these patients were reviewed for similar
      data elements. RESULTS: Of 2,129 patients who received fentanyl for prehospital
      analgesia, only 12 (0.6%) had a vital sign abnormality that could have been
      caused by the administration of fentanyl. Only one (0.2%) of the 611 patients who
      had both field and ED charts reviewed had a vital sign abnormality that
      necessitated a recovery intervention. There were no admissions to the hospital,
      nor patient deaths, attributed to fentanyl use. There was a statistically
      significant improvement in subjective pain scale scores (8.4 to 3.7). Clinically,
      this correlates with improvement from severe to mild pain. CONCLUSION: This study
      showed that fentanyl was effective in decreasing pain scores without causing
      significant hypotension, respiratory depression, hypoxemia, or sedation. Thus,
      fentanyl citrate can be used safely and effectively for pain management in the
      out-of-hospital arena.

PMID- 16418085
TI  - A comparison of rapid-sequence intubation and etomidate-only intubation in the
      prehospital air medical setting.
AB  - OBJECTIVES: To compare laryngoscopy conditions produced by etomidate-only
      intubation (EOI) with those produced by rapid-sequence intubation (RSI) in the
      prehospital air medical setting. METHODS: A prospective crossover trial design
      used two helicopters staffed by the same flight paramedics and nurses. Each
      aircraft used an EOI protocol (0.3 mg/kg) for six months. An RSI protocol using
      the same dose of etomidate plus succinylcholine (1.5 mg/kg) was used for the
      alternate six months. Laryngoscopy conditions were graded by three scales: 1) a
      formal Laryngoscopy Grading Scale (LGS), 2) the Percentage of Glottic Opening
      (POGO) score, and 3) subjective overall intubation difficulty using a Likert
      scale of 1 (very easy) to 5 (very difficult). Orotracheal intubation success was
      also recorded. RESULTS: Forty-nine patients were intubated using the EOI (n = 24)
      and RSI (n = 25) protocols. Mean age was 38 years, 76% were male, and 90% were
      intubated for trauma. Fifteen (63%) of the 24 EOI patients required additional
      etomidate (n = 3) or RSI (n = 12) to allow intubation, while one (4%) of the 25
      RSI patients required additional medication dosing (p < 0.0001). Laryngoscopy
      conditions were assessed for all patients. Good or acceptable conditions as
      assessed by the LGS were seen in 79% of RSI patients and 13% of EOI patients (p <
      0.0001). Mean rates of POGO visualization were 60% with RSI and 12% with EOI (p <
      0.0001). Mean global intubation difficulty scores were 3.0 (moderate) with RSI
      and 4.7 (difficult to very difficult) with EOI (p < 0.0001). Ninety-two percent
      of the patients undergoing RSI and 25% of the EOI patients were successfully
      orotracheally intubated (p < 0.0001). CONCLUSIONS: Patients receiving RSI had
      better laryngoscopy conditions and were easier to intubate than patients
      receiving EOI. Intubation success rate was higher with RSI.

PMID- 16418086
TI  - Evaluating state capacity to collect and analyze emergency medical services data.
AB  - BACKGROUND: Centralized emergency medical services (EMS) data collection is
      critical to evaluating EMS system effectiveness, yet a general lack of EMS data
      persists at local, state, and national levels. OBJECTIVE: To assess state
      capacity to collect, analyze, and utilize EMS data. METHODS: Information was
      gathered through state site visits and surveys from 54 states and U.S.
      territories in spring 2003 regarding EMS data-collection systems. Survey results
      were used to create 11 broad indicators that assess state data system
      infrastructure, collection methods, compliance with data standards, and data
      uses. RESULTS: States and territories on average met 59% of the EMS data system
      indicators, with four states meeting all 11 indicators and two states meeting
      none. Seventy-six percent of the states reported having state-level EMS data
      collection systems, and 78% reported having authority to collect EMS data.
      However, most state EMS data sets were not capturing information on all EMS
      incidents, and only 46% of the states had data dictionaries containing at least
      three-fourths of nationally recommended EMS data elements. In addition, only 33%
      of the states had linked EMS data with other health data sets to analyze EMS
      system operations and patient outcomes. CONCLUSION: While EMS data systems exist
      in the majority of states, continued attention and resources are needed for state
      level EMS data system development to improve capacity for evaluation of emergency
      medical services.

PMID- 16418087
TI  - Do EMS personnel identify, report, and disclose medical errors?
AB  - OBJECTIVE: To evaluate self-reports of prehospital providers' error frequency,
      disclosure, and reporting in their actual practice and in hypothetical scenarios.
      METHODS: The authors surveyed a convenience sample of prehospital providers
      attending a statewide emergency medical services conference using a two-part
      instrument. Part 1 evaluated respondent demographics and actual practice
      patterns. Part 2 used hypothetic scenarios to assess error identification,
      disclosure, and reporting patterns. Descriptive statistics and Fisher's exact
      tests were used to characterize demographics and practice patterns. For
      hypothetical scenarios, the authors calculated mean responses with 95% confidence
      intervals (CIs) to assess error identification, anticipated disclosure, and
      reporting patterns. RESULTS: The response rate was 88% (372/425). Analysis was
      limited to 283 (75% of 372) respondents who were emergency medical technicians
      and had complete data. In the previous year, 157 (55%) providers identified no
      errors in practice, 100 (35%) reported one or two errors, and 26 (9%) identified
      more than two errors. In approximately half of cases, identified errors were
      reported to the receiving provider, or supervisor. In hypothetical cases, severe
      errors were identified 93% (95% CI 92-94) of the time, but the ability of
      providers to identify mild errors significantly varied. In all scenarios,
      respondents were much more likely to report errors to the receiving hospital,
      their supervisor, and their medical director than to patients. CONCLUSIONS:
      Prehospital providers demonstrate the capacity to identify, report, and, to a
      lesser extent, disclose errors in hypothetical scenarios but may not apply these
      skills uniformly in their own practices. Enhancing error management skills in
      prehospital clinical practice will require focused education and training.

PMID- 16418088
TI  - What are the characteristics and outcomes of nontransported pediatric patients?
AB  - BACKGROUND: The authors have demonstrated that 28% of children cared for by
      paramedics are not transported to hospital by ambulance. OBJECTIVE: To determine
      the characteristics, reasons, and outcomes for this nontransported population.
      METHODS: This was a prospective cohort study in a single city with a two-tiered
      emergency medical services system. Enrolled were all children aged < 16 years
      assessed by paramedics but not transported to hospital over a five-month period.
      Data were collected from ambulance call reports, phone interviews, and hospital
      charts. Descriptive statistics were used. RESULTS: Over five months, there were
      345 nontransported pediatric patients with a mean age of 6 years, and 58.3% were
      male. The dispatch priority was urgent in 68.1% of cases and prompt in 30.4% of
      cases. The primary problems were almost evenly split between trauma (50.7%) and
      medical (45.2%) causes. Paramedics listed the following reasons for nontransport:
      parent will take the child to a physician (27.8%), parent will monitor the
      child's condition (25.8%), and no reason documented (46.4%). Phone interview was
      conducted with 106 parents (30.7%): 76.4% believed there was a true emergency at
      the time of the 9-1-1 call, 75.5% stated that the paramedics did not recommend
      that the child be transported to hospital by ambulance, and 29.2% stated that the
      paramedics said ambulance transport was not necessary. Fifty-one children were
      seen in an emergency department (ED) within 48 hours of the 9-1-1 call. The
      majority (91.3%) were discharged home from the ED, while a small minority (8.7%)
      were admitted to hospital. No deaths were reported. CONCLUSIONS: Most
      nontransported children did not require immediate or urgent medical care. Both
      parents and paramedics gave input into the nontransport decision, and the short
      term outcome of this population appeared to be good. Paramedic documentation for
      the reasons for nontransport should be improved.

PMID- 16418089
TI  - Scene transport of pediatric patients injured at winter resorts.
AB  - OBJECTIVE: To examine the characteristics of pediatric patients (age =16 years)
      injured at winter resort scenes and transported by helicopter emergency medical
      services (HEMS) or ground EMS (GEMS) ambulance services to regional trauma
      centers. METHODS: Between 1997 and 2001, a total of 119 patients (GEMS = 69; HEMS
      = 50) were identified from trauma registries and HEMS transport records.
      Demographic data, initial vital signs, hospital interventions, and discharge
      status of the two groups were examined. RESULTS: The distributions of gender,
      initial vital signs, Injury Severity Score (ISS; either = or > 15), intensive
      care unit (ICU) length of stay (LOS), total hospital LOS, and home discharge
      status were similar between the two groups (p = 0.05). Patients transported by
      HEMS were older (14 +/- 2 vs. 10 +/- 4, p < 0.001), less likely to be admitted to
      the hospital (73% vs. 98.5%; p < 0.001), and more likely to have multiple
      injuries [13 (27%) vs. 8 (11.6%), p = 0.032]. The GEMS patients had a higher rate
      of isolated extremity [33 (80.5%) vs. 8 (19.5%)] and thoracoabdominal [11 (73.3%)
      vs. 4 (26.7%)] injuries. The high orthopedic injury rate in the GEMS patients
      contributed to a higher rate of surgery in this group (45% vs. 24%, p = 0.028).
      Regardless of transport mode, patients requiring immediate interventions
      (intubation, chest tube placement, or blood product administration) had either a
      depressed level of consciousness (GCS = 12) on emergency department arrival or
      thoracoabdominal injuries. No deaths were recorded. CONCLUSIONS: Patients
      transported by HEMS and GEMS had similar hospital characteristics but different
      injury patterns. A prospective study examining the initial triage of pediatric
      patients injured at winter resorts would help to determine which subset of
      patients are best served by HEMS transport.

PMID- 16418090
TI  - Do medications affect vital signs in the prehospital treatment of acute
      decompensated heart failure?
AB  - INTRODUCTION: Prehospital treatment of patients with acute decompensated heart
      failure (ADHF) has been shown to decrease mortality and morbidity. Vital sign
      changes have been proposed as clinical endpoints in the evaluation of prehospital
      treatment for this condition. OBJECTIVE: To examine the effect of prehospital
      treatments on vital signs among patients with ADHF. METHODS: Records of an urban
      emergency medical services system from September 1, 2002, through September 1,
      2003, were queried for patients who had a paramedic impression of shortness of
      breath or respiratory distress and had received nitroglycerin and/or furosemide.
      Demographics, initial and repeat vital signs (blood pressure, heart rate,
      respiratory rate, and oxygen saturation), and medications and doses were
      collected. RESULTS: Three hundred nineteen patients were included; the average
      age was 77 (+/-12) years and 47% were male. Treatments administered to these
      patients included nitroglycerin, 296 (93%); furosemide, 194 (61%); albuterol, 189
      (59%); aspirin, 57 (18%); morphine, 20 (6%); and prehospital intubation, 15 (5%).
      Patients were initially hypertensive [mean +/- standard deviation of systolic
      blood pressure (SBP) was 167 +/-37 mm Hg], tachycardic (heart rate 106 +/- 24
      beats/min), tachypneic (respiratory rate 33 +/- 7 breaths/min), and hypoxic
      (pulse oximetry 88% +/- 9.5%). After treatment, mean changes included decreases
      (95% confidence interval) in (SBP), -10.6 mm Hg (-14.1 to -7.1), heart rate, -2.3
      beats/min (-4.0 to -0.7), and respiratory rate, -3.0 (-3.6 to -2.3), and an
      increase in oxygen saturation, +8.2 (7.1 to 9.3). Changes in blood pressure and
      oxygen saturation after treatment correlated with initial values. There was no
      independent association of either nitroglycerin, furosemide, albuterol, or
      morphine with improvement in vital signs. CONCLUSION: Prehospital patients with
      ADHF are a heterogeneous group of patients with significant variability in vital
      signs. The change in systolic blood pressure or oxygen saturation after treatment
      depends greatly on the patient's starting point. There was no association of
      either nitroglycerin or other medications with the improvement in vital signs.

PMID- 16418091
TI  - Comparison of the Ferno Scoop Stretcher with the long backboard for spinal
      immobilization.
AB  - OBJECTIVES: Spinal immobilization is essential in reducing risk of further spinal
      injuries in trauma patients. The authors compared the traditional long backboard
      (LBB) with the Ferno Scoop Stretcher (FSS) (Model 65-EXL). They hypothesized no
      difference in movement during application and immobilization between the FSS and
      the LBB. METHODS: Thirty-one adult subjects had electromagnetic sensors secured
      over the nasion (forehead) and the C3 and T12 spinous processes and were placed
      in a rigid cervical collar, with movement recorded by a goniometer (a motion
      analysis system). Subjects were tested on both the FSS and the LBB. The sagittal
      flexion, lateral flexion, and axial rotation were recorded during each of four
      phases: 1) baseline, 2) application (logroll onto the LBB or placement of the FSS
      around the patient), 3) secured logroll, and 4) lifting. Comfort and perceived
      security also were assessed on a visual analog scale. RESULTS: There was
      approximately 6-8 degrees greater motion in the sagittal, lateral, and axial
      planes during the application of the LBB compared with the FSS (both p < 0.001).
      No difference was found during a secured logroll maneuver. The FSS induced more
      sagittal flexion during the lift than the LBB (p < 0.001). The FSS demonstrated
      superior comfort and perceived security. CONCLUSION: The FSS caused significantly
      less movement on application and increased comfort levels. Decreased movement
      using the FSS may reduce the risk of further spinal cord injury.

PMID- 16418092
TI  - The changing incidence of ventricular fibrillation in Milwaukee, Wisconsin (1992
      2002).
AB  - OBJECTIVES: To investigate the changes in annual incidence and survival of out-of
      hospital cardiac-etiology arrests of different initial rhythms, particularly
      ventricular fibrillation (VF) and ventricular tachycardia (VT), among adults (>
      21 years old) in Milwaukee County between 1992 and 2002 and establish
      correlations with patient and emergency medical services (EMS) system-dependent
      factors. METHODS: The study was a retrospective, observational study of all adult
      (> 21-year-old) patients with out-of-hospital cardiac-etiology arrests with
      identifiable rhythm and resuscitation attempted by the Milwaukee County EMS
      system from 1992 to 2002. Nine thousand one hundred seventy cases were enrolled.
      Primary outcome measures were changes in annual incidence of initial cardiac
      arrest rhythm, with a focus on VF/VT. Secondary outcome measures were changes in
      survival to hospital admission and hospital discharge for VF and VT. Patient and
      EMS system factors potentially affecting the outcome measures were identified and
      modeled using multivariate logistic regression. RESULTS: The incidence of out-of
      hospital VF/VT arrests decreased steadily from 37.1 per 100,000 in 1992 to 19.4
      per 100,000 in 2002. While the incidences of pulseless electrical activity and
      overall cardiac arrest remained unchanged, the incidence of asystole during the
      study period increased from 27.3/100,000 to 44.9/100,000. Multivariate regression
      analyses revealed that age < 80 years, male gender, white race, previous cardiac
      surgery, and cardiac history were patient-dependent factors predictive of VF/VT.
      Witnessed arrest, public location, and shorter response time were EMS system
      dependent factors predictive of VF/VT. Based on observed trends, none of these
      correlated factors could explain the decrease in the incidence of VF/VT arrests.
      Rates of patient survival to hospital admission and discharge were not
      significantly changed over time. EMS system factors predictive of survival to
      admission and discharge were witnessed arrest, public location, and decreased
      number of defibrillations. Prior cardiac surgery and absence of chronic problems
      were the only patient factors predictive of survival to hospital admission but
      were not significantly related to survival to hospital discharge. CONCLUSIONS:
      The incidence of out-of-hospital cardiac arrests in adult patients with
      presenting rhythm of VF/VT declined, while an increase in asystole occurred. This
      was not explained by any patient or EMS system-dependent factor. Rate of survival
      for VF/VT arrest did not significantly change over time. Survival was primarily
      influenced by EMS system factors and unrelated to patient-dependent factors.

PMID- 16418093
TI  - A randomized, controlled comparison of cardiopulmonary resuscitation performed on
      the floor and on a moving ambulance stretcher.
AB  - BACKGROUND: Recent studies have demonstrated that cardiopulmonary resuscitation
      (CPR) of poor quality is associated with worsened outcomes. OBJECTIVE: To compare
      the quality of CPR delivered on the floor with the quality of CPR delivered on a
      moving stretcher. The authors hypothesized that CPR performed on the floor would
      be superior to that performed on a moving stretcher. METHODS: A randomized,
      crossover experimental design was used. Subjects included emergency medical
      technician students, paramedic students, and emergency medicine residents. Two
      member teams were randomly assigned to perform two-rescuer CPR on a manikin
      either on the floor or on a moving stretcher. After a 5-minute rest, the teams
      performed CPR under the opposite condition. Compression and ventilation data were
      collected using a recording resuscitation manikin. Dependent variables were
      compression depth, compression rate per minute, percentage of correct chest
      compressions, tidal volume, and percentage of correct ventilations. Data were
      compared using two-tailed paired t-test. RESULTS: Sixty-two subjects completed
      the study. The mean compression depth performed on the floor (39 +/- 9 mm) was
      greater than that on a moving stretcher (28 +/- 9 mm) (p < 0.001). The mean rates
      of chest compressions on the floor (110 +/- 17 beats/min) and on a moving
      stretcher (113 +/- 21 beats/min) were not different (p = 0.49). The percentage of
      correct compressions performed on the floor (54% +/- 40%) exceeded that on a
      moving stretcher (21% +/- 29%)(p < 0.001). The percentage of correct ventilations
      performed on the floor (43% +/- 26%) was greater than that on a moving stretcher
      (24% +/- 21%)(p < 0.04). CONCLUSIONS: Chest compression and ventilation quality
      of CPR performed on the floor was superior to that of CPR performed on a moving
      stretcher in this manikin model. The quality of CPR while moving was
      significantly compromised.

PMID- 16418094
TI  - Effects of an educational intervention on prehospital pain management.
AB  - INTRODUCTION: Pain is a common symptom evaluated by emergency medical services
      (EMS) providers. Hospital pain management programs began in the early 1990s based
      on a multidisciplinary approach and principles of total quality improvement. To
      date, these programs have had limited exposure in the prehospital setting.
      OBJECTIVES: To evaluate the effects of a pain management educational intervention
      (EI) for paramedic caregivers. METHODS: All ambulance providers from ten urban
      and suburban fire departments and two private ambulance companies participated in
      a three-hour EI during a quality improvement project. A survey was performed
      prior to the EI and repeated one month after the EI. A two-month collection of
      EMS runs for pain complaints was performed prior to the EI and repeated one month
      after the EI. Data analysis was performed using descriptive statistics and chi
      square tests. RESULTS: The authors reviewed 397 surveys and 439 EMS runs for
      pain. Overall, after the EI, paramedics' knowledge of basic pain management
      principles increased from 57.3% to 74.9% (17.5%; 95% confidence interval (CI):
      14.9%-20.2%; p < 0.001). Paramedics' utilization of nonpharmacologic pain
      therapies improved by 32.2% (95% CI: 25.3%-39.2%; p < 0.001), but there was no
      significant change in the use of pain medication (20.2% to 24.5%). There were
      51.0% (95% CI: 44.1%-57.9%; p < 0.001) improvement in documentation of pain
      severity, 24% (95% CI: 21.2%-26.8%; p < 0.001) improvement in documentation of
      pain characteristics, and 13% (95% CI: 7.4%-18.7%; p < 0.001) improvement in pain
      reassessment following intervention. CONCLUSION: As a result of a three-hour
      educational intervention, paramedics had an increased understanding of pain
      principles, were more likely to provide prehospital nonpharmacologic pain
      therapy, and were more likely to document the results of their interventions.

PMID- 16418095
TI  - Difficulty breathing: agreement of paramedic and emergency physician diagnoses.
AB  - OBJECTIVE: To determine the diagnostic accuracy of paramedics treating patients
      who have called an ambulance for "difficulty breathing." METHODS: A retrospective
      study of all ambulance call reports generated by one ambulance over a one-year
      period with the dispatch complaint of "difficulty breathing" taken to the
      hospital. The paramedic diagnosis on the call report was compared with the
      emergency department (ED) physician diagnosis, which was used as the "gold
      standard." RESULTS: A total of 244 ambulance reports were reviewed. For patients
      complaining of "difficulty breathing," paramedics achieved 86.4% sensitivity and
      86.6% specificity for diagnosing cardiac disease, 71.4% sensitivity and 93.6%
      specificity for respiratory disease, and 82.1% sensitivity and 91% specificity
      for other disease processes. There was an interrater agreement of 81.1% between
      paramedic and ED physician, producing a kappa of 0.71, interpreted as good,
      approaching excellent, agreement. CONCLUSION: Paramedics are able to identify the
      disease process category in patients dispatched as having "difficulty breathing,"
      with a moderate degree of accuracy.

PMID- 16418096
TI  - Predicting prehospital care students' first-year academic performance.
AB  - OBJECTIVES: To answer two research questions: First, can previously identified
      factors relating to academic performance be used to predict first-year academic
      success for students undertaking a newly developed and vocationally oriented
      prehospital care course delivered in a rural setting? Second, can the study's
      findings be used to develop appropriate student selection criteria to assist in
      the admission of students into relevant tertiary studies or the prehospital care
      industry? METHODS: A retrospective review of all first-year, on-campus
      prehospital care students enrolled in a vocational course at a rural Australian
      university from 1998 to 2001 was conducted. Six predictors of academic
      performance were examined, namely: University Admission Index (UAI),
      postsecondary educational qualifications, student entry type (traditional or
      mature-aged), previous health-related experience, gender, and background (rural
      or urban). Three dependent variables assessed academic performance: grade point
      average (GPA) of students who completed all required first-year subjects, GPA of
      students who completed at least one subject in the first year, and the student's
      ability to successfully complete the first year. RESULTS: UAI > 50, previous
      health-related experience, postsecondary educational qualifications, background,
      student entry type, and gender were all found to be significant predictors of
      first-year academic performance in selective cohorts. In addition, a combination
      of predictors produced higher GPAs than did any single predictor. CONCLUSION:
      Academic performance of first-year students in the prehospital care discipline
      can be predicted given the appropriate selection variables. Admission selection
      can be assisted with the generated Student Selection 001.

PMID- 16418097
TI  - EMTs' attitudes' toward death before and after a death education program.
AB  - OBJECTIVE: To test the hypothesis that emergency medical technicians' (EMTs')
      attitudes toward death will change after exposure to a death education program.
      METHODS: A convenience sample of 83 rural EMTs participated in this pretest
      posttest study after exposure to an educational program related to death. Intact
      groups of EMTs were randomly assigned to one of three conditions. The short
      intervention group received a two-hour class solely on making death
      notifications. The long-intervention group received a 16-hour, two-day workshop
      based on the Emergency Death Education and Crisis Training (EDECT(SM)) program.
      The control group received a program about toxicology. Each participant completed
      a questionnaire with items structured in a Likert five-point format with
      "strongly agree" and "strongly disagree" as the anchors. RESULTS: Before the
      training programs, most (77%) participants reported that an EMT's actions impact
      the family's grief. Less than half (43%) reported that an EMT's role should
      include making a death notification. The majority (84%) reported that their
      training was inadequate to make a death notification or to help the family with
      their grief. Most (84%) felt uncomfortable making a death notification. Those
      EMTs in the long-intervention group were significantly more likely (92%) to feel
      that their training was adequate after the intervention when compared with those
      EMTs in the short-intervention group (43%) or those in the control group (21%).
      CONCLUSION: The data showed that EMTs' attitudes toward death changed after
      exposure to a training program about death.

PMID- 16418098
TI  - FAST ultrasound as an adjunct to triage using the START mass casualty triage
      system: a preliminary descriptive system.
AB  - OBJECTIVE: To determine whether the FAST examination might be a useful adjunct to
      simple triage and rapid treatment (START) in the secondary triage of mass
      casualty victims already classified as delayed (Yellow). METHODS: A retrospective
      chart review was conducted of all adult trauma patients evaluated by the trauma
      surgery service at a level 1 trauma center between January 1 and December 31,
      2003. Patients were retrospectively triaged to one of three START categories:
      immediate (Red), delayed (Yellow), or expectant (Black). The FAST results were
      obtained from the medical records. RESULTS: FAST results were available for 359
      patients, of which 27 were classified as positive. Twenty (6.9%) of 286 patients
      retrospectively triaged as delayed (Yellow) had positive FAST studies. Of these,
      six underwent operative intervention within 24 hours of arrival. A total of 232
      patients had both FAST and computed tomography (CT) studies performed, of which
      19 FAST studies were inconclusive. In the remaining 213 patients, six of 27 had
      falsely positive studies, while 24 of 186 had falsely negative studies.
      CONCLUSIONS: Portable ultrasound technology might have identified 20 delayed
      (Yellow) patients with evidence of hemoperitoneum, thereby expediting evacuation
      to definitive care. However, only 30% of these patients subsequently underwent an
      operative intervention within 24 hours of arrival. Both over- and undertriage
      were significant problems. As such, the current study does not support the
      routine use of FAST ultrasound as a secondary triage tool.

PMID- 16418099
TI  - First responder in personal protective equipment with unknown illness during a
      disaster drill.

PMID- 16418102
TI  - Behavioral assessment of couples' communication in female orgasmic disorder.
AB  - Communication problems are believed to play a central role in many sexual
      dysfunctions. The present study behaviorally assessed communication patterns
      within heterosexual couples in which the woman was experiencing female orgasmic
      disorder and within two groups of control couples. The sexually dysfunctional
      couples evidenced significantly poorer communication than controls, primarily but
      not exclusively when discussing sexual topics. Specifically, women with orgasmic
      disorder or their male partners demonstrated more blame and less receptivity. We
      discuss the etiologic and treatment implications of these findings.

PMID- 16418103
TI  - Effects of a new functional-sexological treatment for premature ejaculation.
AB  - Premature ejaculation is the most-prevalent sexual problem in men. Various
      treatments have been developed to increase control over the moment of
      ejaculation, with two of the most frequent techniques used in behavior therapy
      being the squeeze method developed by Masters and Johnson (1970) and the "stop
      and-start" technique described by Semans (1956). These treatments are effective
      and improve matters in most cases. However, couples can be averse to using them,
      with some women reluctant to squeeze their partner's penis and some couples
      unwilling to interrupt sexual interaction once initiated. Under a new functional
      sexological treatment intended to improve control over the moment of ejaculation,
      men learn how to control their arousal without having to interrupt sexual
      activity. In this study, we compared three groups of couples in which the man
      suffered from premature ejaculation. One followed the new functional-sexological
      treatment, another followed a behavioral treatment--including the squeeze and
      stop-and-start techniques--and a control group was placed on a waiting list. We
      used several questionnaires to assess the effects of the various treatments.
      Moreover, subjects provided an objective measure of duration of intercourse from
      penetration to ejaculation. These measures were taken pre- and posttreatment and
      at three-month follow-up. We ran analyses of variance to assess the effects of
      the treatments. Results indicate that the new treatment is very effective. We
      observed significant improvements in duration of intercourse, sexual
      satisfaction, and sexual functioning. The subjects in the behavioral treatment
      group obtained similar results. Furthermore, subjects from both groups were
      satisfied with their respective treatment.

PMID- 16418104
TI  - Reliability and validity of the Sexual Interest and Desire Inventory-Female (SIDI
      F), a scale designed to measure severity of female hypoactive sexual desire
      disorder.
AB  - The Sexual Interest and Desire Inventory-Female (SIDI-F) is a 13-item scale
      developed as a clinician-administered assessment tool to quantify the severity of
      symptoms in women diagnosed with hypoactive sexual desire disorder (HSDD). The
      present investigation assessed the reliability and validity of the SIDI-F as a
      measure of HSDD severity. Results show that the SIDI-F exhibits excellent
      internal consistency, with Cronbach's alpha of 0.9. The validity of the SIDI-F as
      a measure of HSDD severity was confirmed by a number of observations. Women with
      a clinical diagnosis (Diagnostic and Statistical Manual of Mental Disorders [DSM
      IV-TR; American Psychiatric Association, 2000]) of HSDD had significantly lower
      SIDI-F scores than women not meeting diagnostic criteria for any subtype of
      female sexual dysfunction and women diagnosed with female orgasmic disorder.
      There was a high correlation between scores on the SIDI-F and scores on the
      Female Sexual Function Index (FSFI; Rosen et al., 2000) and an interactive voice
      response version of the Changes in Sexual Functioning Questionnaire (CSFQ;
      Clayton, McGarvey, & Clavet, 1997; Clayton, McGarvey, Clavet, & Piazza, 1997),
      two validated measures that assess general female sexual dysfunction. In
      contrast, there was a poor correlation between SIDI-F scores and scores on a
      slightly modified Marital Adjustment Scale (Locke, Wallace, 1959; MAS), an
      assessment of general (nonsexual) relationship satisfaction. Taken together, the
      results of the present investigation indicate that the SIDI-F is a reliable and
      valid measure of HSDD severity, independent of relationship issues.

PMID- 16418105
TI  - Confirmatory factor analysis of a Spanish version of the sex fantasy
      questionnaire: assessing gender differences.
AB  - The objective of this study was to validate the factor structure of Wilson's Sex
      Fantasy Questionnaire (SFQ; Wilson, 1978; Wilson & Lang, 1981) using a Spanish
      version. In order to do this, we conducted confirmatory factor analysis on two
      nonclinical samples containing 195 men and 315 women. Both groups were tested for
      the structure proposed by Wilson and also for some alternative models.
      Confirmatory factor analysis showed that four factors were reasonably distinct,
      especially for the men. We proposed shortened version of the instrument that
      would have sufficient psychometric guarantees for assessing sexual fantasies in
      both genders. This abridged version improved the fit of the four-factor oblique
      factor equally for both the samples of men and women. In the light of the results
      of the validation hypothesis established with some criterion variables (dyadic
      sexual desire, unconventional sex, homophobia), we discuss discrepancies between
      both versions.

PMID- 16418106
TI  - Effects of administering sexually explicit questionnaires on anger, anxiety, and
      depression in sexually abused and nonabused females: implications for risk
      assessment.
AB  - Human sexuality researchers and institutional review boards often are concerned
      about the sensitive nature of the information that they obtain and whether this
      type of research increases the psychological risks to participants. To date,
      there are almost no empirical data that address this issue. We administered state
      and trait measures of anger, anxiety, and depression to 207 females who were
      administered four questionnaires that asked them to reveal highly sensitive,
      sexually explicit information, including questions regarding childhood sexual
      abuse. Then they were readministered the state and trait measures of distress. We
      found no significant differences, even among those who reported being sexually
      abused as children, suggesting that such studies do not significantly increase
      the risk of psychological harm to participants.

PMID- 16418107
TI  - Prevalence and comorbidity of sexual dysfunctions in a Portuguese clinical
      sample.
AB  - We investigated the prevalence and comorbidity of sexual dysfunction in a
      clinical Portuguese sample. A total of 96 participants (47 females and 49 males
      with a diagnosis of sexual dysfunction (DSM-IV; American Psychological
      Association, 1994) assigned by a group of trained sex therapists) answered the
      Female Sexual Function Index (FSFI; Rosen et al., 2000) and the International
      Index of Erectile Function (IIEF; Rosen et al., 1997). Results indicated erectile
      dysfunction (70%) and female hypoactive sexual desire disorders (40.4%) as the
      most prevalent complaints, with premature ejaculation (22.4%), vaginismus
      (25.5%), and female orgasmic disorder (21.3%) also showing relevant prevalences.
      Comorbidity studies indicated higher levels of overlapping among female sexual
      difficulties with strong associations between desire, subjective arousal, and
      orgasmic disorders, as well as between dyspareunia and vaginismus.

PMID- 16418108
TI  - Comorbidity between social phobia and premature ejaculation: study on 242 males
      affected by sexual disorders.
AB  - Several studies have reported high comorbidity between psychiatric and sexual
      disorders, particularly between anxiety and mood disorders and sexual
      dysfunction. The goal of the present study is to examine the comorbidity between
      premature ejaculation and Axis I psychiatric disorders. Of 242 males referred to
      an outpatient clinic of sexology between November 2000 and July 2003, 52 were
      diagnosed with premature ejaculation (PE). These patients were also administered
      the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID; First,
      Spitzer, Gibbon, & Williams, 1995) for the evaluation of Axis I psychiatric
      disorders and a modified SCID based on Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV; American Psychiatric Association, 2000) criteria for
      the evaluation of sexual disorders. We also determined the age of onset of the
      disorders. We found that 21.5% of the overall clinical population was affected by
      PE, and 64.4% of PE patients were affected by at least one Axis I psychiatric
      disorder. PE was highly associated (p=0.015) with social phobia (SP), with an
      odds ratio of 2.55. The debut of SP preceded the onset of PE. Social phobia may
      represent risk factor for the development of PE, and adrenergic hyperactivity may
      represent a pathophysiology common to both disorders.

PMID- 16418112
TI  - Editorial.

PMID- 16418113
TI  - Sex differences in high-risk premature infants' asymmetric movement development.
AB  - High-risk premature infants are likely to show altered patterns in the
      development of reflexes and postural reactions. This study used the Modified
      Measure of Behavioral Laterality (M-MOBL) neonatal assessment to explore
      differences in reflex and postural reactions among 26 male and female high-risk,
      premature infants born between 23 and 26 weeks gestational age. M-MOBL scores at
      33-36.5 weeks were compared to those at 36.5-40 weeks of age, shortly before
      hospital discharge. The M-MOBL data were analyzed using the categorical method
      (CATMOD) repeated measures analysis of variance (ANOVAs) to compare the
      development of asymmetric movement patterns in: (1) non-injured and CNS-injured
      high-risk, premature infants, (2) control and experimental infants who received
      multi-sensory stimulation, and (3) males and female infants. Consistent with
      previously published reports of a right-(R) bias for healthy, full-term infant's
      movements, we found that high-risk premature females showed R-sided biases by 35
      37 weeks post-conceptional age (PCA) for head turning responses and reflexes
      evoked by upper-body stimulation (i.e., palmar grasp, asymmetric tonic neck
      reflex (ATNR), incurvation). High-risk premature males however showed no
      significant difference in strength and coordination between the R-side and the
      left (L), as measured by the M-MOBL, in most of these upper-body movements tested
      at 35-37 weeks PCA. Neither premature males nor females showed asymmetries in
      foot and leg reflexes (placing, plantar grasp, Babinski). Healthy, full-term
      males did not show asymmetries in these reflexes either. However, full-term
      females showed an R-bias. With further research, the M-MOBL may become a useful
      instrument for early identification of infants with atypical CNS development who
      later exhibit atypical laterality patterns.

PMID- 16418114
TI  - The developmental test of visual perception-2 normative study on the visual
      perceptual function for children in Hong Kong.
AB  - This research study intended to investigate the visualperceptual performance of
      children in Hong Kong by comparing them to the accepted norms on the
      Developmental Test of Visual Perception-2nd edition. The research examined
      whether there was significant difference in child's gender, age, and grade. The
      normative study recruited two hundred and eight-nine children between the ages of
      6 and 7 in normal primary schools in Hong Kong. Results indicated that there was
      a ceiling effect in eye-hand coordination, position in space and spatial
      relations subtests. Grade differences were found to be significant in all
      subtests except eye-hand coordination and visual-motor speed. On the other hand,
      there were no statistical difference in the test scores between boys and girls
      except on copying and figure-ground subtests. It is concluded that there is a
      strong need to ensure that norms for visual-perceptual tests are appropriate for
      the specific cultural groups being assessed.

PMID- 16418115
TI  - Study on the social maturity, self-perception, and associated factors, including
      motor coordination, of children with attention deficit hyperactivity disorder.
AB  - This study was designed to identify characteristics of social maturity and self
      perception in children with attention deficit hyperactivity disorder (ADHD) and
      to elucidate associated factors, including motor coordination. The subjects were
      15 children (14 boys and 1 girl, in elementary school grades 3 to 6). Their
      characteristics were assessed with the Movement Assessment Battery for Children
      (M-ABC), the Japanese version of the Social Maturity Scale-R (S-M scale), and
      Harter's Self Perception Profile for Children (SPPC). The results of the study
      suggested that most of the subjects had some degree of motor problem and delay of
      social maturity. They also suggested an association between social maturity and
      static-dynamic balance, which was one of the indices of motor coordination.

PMID- 16418116
TI  - Performance on extremely low birthweight children at 5 years of age on the Miller
      Assessment for Preschoolers.
AB  - The purpose of this geographically defined national study was to evaluate the
      performance of extremely low birthweight children (ELBW < 1000 g) born in Iceland
      in 1991-1995 and compare to a cohort of matched control children born full term.
      The Miller Assessment for Preschoolers (MAP) was used to provide an overall
      profile of 32 ELBW children and 55 control children at 5 years of age. The
      results indicated that score patterns on the MAP between ELBW and normal
      birthweigt children differ. The differences were significant on the Total Score,
      and the Foundations, Coordination, and Complex-Tasks Indices. This study found
      that the ELBW group had specific problems in basic motor tasks, coordination, and
      fine motor skills. The results validate the need for early assessment, regular
      follow up, and consultation to promote optimal task performance and social
      participation of children born prematurely.

PMID- 16418119
TI  - Gender disparity of successful aging in Taiwan.
AB  - The purpose of this longitudinal study was to examine the association of gender
      on successful aging during a 6-year follow-up study. Data were drawn from the
      1989, 1993, 1996, and 1999 Survey of Health and Living Status of the Elderly in
      Taiwan, a national representative population survey of 4,049 participants aged 60
      years or older; 43% were women. Successful aging indicators were defined as
      physical (absence of disease and physical disability), mental (normal cognitive
      function and absence of depression), and social (good social support and
      participation in productive activities). Gender differences related to successful
      aging during the 6 years were analyzed with Cox proportional hazards regression
      model. Significant disparities were found between elderly men and women in
      activities of daily living (ADL), instrumental activities of daily living (IADL),
      cognitive function, depressive symptoms, social support and productive
      activities. When the data included individuals who were deceased, elderly women
      showed better maintenance of ADL and less vulnerability to IADL impairment than
      elderly men. However, when the analysis included only survivors during the follow
      up, the elderly were more likely to be impaired in IADL and cognitive function,
      have depressive symptoms, and lack engagement in productive activities.
      Cumulative disadvantage was associated with health disparities in elderly women.
      This research demonstrates the need to develop gender-sensitive policies.

PMID- 16418117
TI  - Cerebral palsy and chronic pain: a descriptive study of children and adolescents.
AB  - The experiences of chronic pain among children and adolescents with cerebral
      palsy (CP) were examined in this survey-based study. Perspective of both the
      individual and the parent were solicited in a preliminary sample of 20 youths
      with CP, ages 6 to 17 years from a metropolitan area. Selected participants
      completed in-person, structured interviews that focused on quality of life with
      attention to pain experiences. Quantitative data were analyzed descriptively.
      Seventy percent of participants (n = 14) experienced recurrent chronic pain of
      moderate intensity on a daily or weekly basis. Greater than half of those
      participants (n = 9) reported that pain presented a problem for them and
      especially interfered with self-care and with sleep. Pain appears to be a problem
      for many youths with CP, and may create additional interference with routine
      activities of daily living and participation. Further exploration regarding pain
      experiences and the nature of pain interference is warranted in order to address
      development and maintenance of routine activities and participation by children
      and adolescents with CP.

PMID- 16418121
TI  - Gender and somatosensory amplification in relation to perceived work stress and
      social support in Japanese workers.
AB  - To examine gender-related differences in somatization among workers, 490 Japanese
      municipal office employees (248 women) completed the Medical Symptom Checklist,
      Somatosensory Amplification Scale (SSAS), and Profile of Mood States (POMS),
      along with questionnaires on their working environment. In women, SSAS scores
      were positively associated with perceived work stress, and negatively with social
      support levels (both p < 0.01). Female sex was significantly associated with SSAS
      scores (p < 0.01), controlling for the effects of total somatic symptom count,
      POMS tension-anxiety and depression scores, perceived working stress, and social
      support. The phenomenon of somatosensory amplification might be essential in
      estimating gender-specific symptoms in a working population.

PMID- 16418120
TI  - African American women and family planning services: perceptions of
      discrimination.
AB  - OBJECTIVES: The purpose of this study was to examine perceived race-based
      discrimination in obtaining family planning or contraceptive services among
      African American women in the U.S. METHODS: We conducted a 30-minute telephone
      survey with a random sample of 500 African Americans (aged 15-44), which included
      questions about race-based discrimination when obtaining family planning
      services. The present analyses were limited to the 326 women who completed
      interviews. RESULTS: The majority (79%) of women reported having seen a health
      care provider for family planning or birth control services. Of those, 67%
      reported race-based discrimination when obtaining such services. Half of the
      women reported more general experiences of discrimination when obtaining family
      planning services (e.g., poorer service), and 52% reported experiences that
      reflect stereotypes of African American women (e.g., doctor or nurse assumed they
      had multiple sexual partners). Most indicated that experiences of discrimination
      occurred infrequently. Generally, background characteristics were not
      significantly associated with perceived discrimination. However, in multivariate
      models, stronger Black identity, younger age, and lower income were associated
      with reports of discrimination. CONCLUSION: African American women may be
      vulnerable to prejudice within reproductive health care contexts, including
      family planning.

PMID- 16418122
TI  - Teen contraceptive decisions: childbearing intentions are the tip of the iceberg.
AB  - OBJECTIVE: To validate a model we developed while trying to understand why
      pregnant teens so often report that they did not want to become pregnant and
      could have obtained contraceptives before they conceived. METHOD: The study
      enrolled a racially/ethnically diverse group of 351 teenagers. Participants
      completed a questionnaire that asked about teen pregnancy risk factors, the
      expected effects of childbearing, the desire to remain non-pregnant, deterrents
      to contraceptive use, and contraceptive plans. RESULTS: Most participants were
      capable of using contraceptives but at high risk for unintended conception
      because they exhibited numerous sociodemographic risk factors, were unsure that
      pregnancy would affect their lives adversely, and were ambivalent about remaining
      non-pregnant. Believing a boyfriend wanted a baby and the anticipated effect of
      childbearing on 5 specific aspects of life explained 63% of the variance in the
      desire to remain non-pregnant, which, in conjunction with fears about using
      contraceptives, explained 20.5% of the variance in future contraceptive plans.
      CONCLUSIONS: Our new findings that expectations about the effect of childbearing
      explain the desire to remain non-pregnant may well help providers determine why
      teenagers who do not plan to conceive are often willing to allow themselves to do
      so by default. Further research is needed, as the model did not explain
      contraceptive decision-making adequately.

PMID- 16418123
TI  - Gender differences in emotion regulation and relationships with perceived health
      in patients with rheumatoid arthritis.
AB  - Emotion regulation has been associated with perceived health in rheumatoid
      arthritis, which is diagnosed three times more often in women than men. Our aim
      was to examine gender differences in styles of emotion regulation (ambiguity,
      control, orientation, and expression) and gender-specificity of the associations
      between emotion regulation and perceived health (psychological well-being, social
      functioning, physical functioning, and disease activity) in 244 female and 91
      male patients with rheumatoid arthritis. Women reported more emotional
      orientation than men, but did not differ from men with regard to ambiguity,
      control, and expression. Structural equation modelling showed that relationships
      between emotion regulation and perceived health were more frequent and stronger
      for women than men. This held especially for the affective dimension of health,
      while associations were similar for both women and men with regard to social and
      physical functioning. Only for women, the association between ambiguity and
      disease activity was significant, which appeared to be mediated by affective
      functioning. The observations that women are more emotionally oriented than men
      and that emotion regulation is more interwoven with psychological health in women
      than men, support the usefulness of a gender-sensitive approach in research and
      health care of patients with rheumatoid arthritis.

PMID- 16418125
TI  - The incidental orgasm: the presence of clitoral knowledge and the absence of
      orgasm for women.
AB  - Women report anorgasmia and other difficulties achieving orgasm. One approach to
      alleviating this problem is to teach women about the clitoris. This assumes that
      women lack information about the clitoris and that knowledge about the clitoris
      is correlated with orgasm. Using a non-random sample of 833 undergraduate
      students, our study investigates both assumptions. First, we test the amount of
      knowledge about the clitoris, the reported sources of this knowledge, and the
      correlation between citing a source and actual knowledge. Second, we measure the
      correlation between clitoral knowledge and orgasm in both masturbation and
      partnered sex. Among a sample of undergraduate students, the most frequently
      cited sources of clitoral knowledge (school and friends) were associated with the
      least amount of tested knowledge. The source most likely to correlate with
      clitoral knowledge (self-exploration) was among the most rarely cited. Despite
      this, respondents correctly answered, on average, three of the five clitoral
      knowledge measures. Knowledge correlated significantly with the frequency of
      women's orgasm in masturbation but not partnered sex. Our results are discussed
      in light of gender inequality and a social construction of sexuality, endorsed by
      both men and women, that privileges men's sexual pleasure over women's, such that
      orgasm for women is pleasing, but ultimately incidental.

PMID- 16418124
TI  - Adherence to zidovudine for the prevention of perinatal transmission in HIV
      infected pregnant women: the impact of social network factors, side effects, and
      perceived treatment efficacy.
AB  - Adherence to zidovudine (ZDV) prophylaxis among 78 pregnant HIV-infected women
      was measured with 2 physiologic markers. Long-term adherence was measured with
      blood assays for macrocytosis, a clinical indicator of ZDV use; 53 women (67.9%)
      were adherent. Short-term adherence was measured with urine assays for ZDV; 48
      women (61.5%) were adherent. Comparison of urine assay and interview data
      indicated that 29% had not taken the last dose that they reported. Participation
      in HIV support groups and disclosure to the participant's mother were associated
      with better adherence. These social network factors may enable HIV-infected
      pregnant women to cope more effectively with the multiple stressors they face and
      facilitate prenatal care.

PMID- 16418126
TI  - The status of low-income neighborhoods in the post-welfare reform environment:
      mapping the relationship between poverty and place.
AB  - It has long been recognized that children and adults living in poverty are at
      risk for a number of negative outcomes. As inequality in the distribution of
      wealth, income and opportunity has grown in the U.S. during the post-welfare
      reform era, impoverished children and their families have tended to become
      increasingly concentrated in urban low-income neighborhoods. Research evidence
      demonstrates that living in these neighborhoods affects family well-being in
      several key areas: economic and employment opportunity, health and mental health
      condition, crime and safety, and children's behavioral and educational outcomes.
      Using the neighborhood indicator approach, public and nonprofit social service
      agencies will be better positioned to develop a comprehensive and integrated
      service delivery model at the neighborhood level by using neighborhood assessment
      to locate services and utilize neighborhood intervention strategies.

PMID- 16418127
TI  - The status of low-income families in the post-welfare reform environment: mapping
      the relationships between poverty and family.
AB  - Low-income families face an enormous burden to achieve economic security since
      the deterioration of a guaranteed safety net. Health insurance coverage is
      uneven, affordable childcare falls short of demand, and wage earnings
      insufficiently support family needs. This analysis focuses on recent trends in
      family formation, the impact of policy changes on families of color and of
      immigrant status, and explores the daily challenges and coping strategies low
      income families use to survive despite insufficient resources. Four key findings
      emerge from this body of knowledge: (1) Low-income families experience severe
      hardships when relying on cash assistance, work, or a combination of both; (2)
      Low-income families are resilient and resourceful; (3) Low-income families face
      significant barriers to using public and private services along with increasing
      earnings from work; and (4) The quality of life for families of color and
      immigrant families is directly affected by employment and service sector
      practices. Future research needs to focus on identifying the critical unmet needs
      of low-income families.

PMID- 16418128
TI  - Promising programs to serve low-income families in poverty neighborhoods.
AB  - This review of promising programs to address the challenges facing low-income
      families living in distressed neighborhoods reveals three key themes: (1)
      Earnings and asset development programs are used to increase the economic self
      sufficiency of low-income families and include: place-based employment programs,
      a focus on good jobs, the use of work incentives, programs that promote banking,
      car and home ownership, and the use of the Earned Income Tax Credit; (2) Family
      strengthening programs are used to improve health and educational outcomes, as
      well as link families to needed support and benefit services and include: nurse
      home visitation, parenting education, early childhood educational programs, and
      facilitating the receipt of support services; and (3) Neighborhood strengthening
      programs are used to improve features of the neighborhood, collaboration among
      service providers, and resident involvement in neighborhood affairs and include:
      the use of community development corporations, comprehensive community
      initiatives and community organizing strategies.

PMID- 16418129
TI  - Promising practices for meeting the multiple needs of low-income families in
      poverty neighborhoods.
AB  - This review of promising practices for meeting the multiple needs of low-income
      families in poverty neighborhoods reveals four main themes: (1) The challenges
      facing low-income families living in poverty neighborhoods are not discrete-but
      are multidimensional; (2) Integrated family and neighborhood strengthening
      practices, such as the Making Connections (MC) Initiative (funded by the Annie E.
      Casey Foundation), and the Harlem Children's Zone (HCZ), represent innovative
      strategies to address the multifaceted issues facing low-income families living
      in poverty neighborhoods; (3) The organizational structure, challenges and
      successes of the MC and HCZ provide insight into the nature of integrated family
      and neighborhood approaches; (4) A framework for the design of an integrated
      family and neighborhood program includes a focus on internal organizational
      processes, neighborhood processes, and external processes. This framework can
      assist social service agencies in moving their services toward a more integrated
      family and neighborhood approach.

PMID- 16418130
TI  - Living in poverty in America today.
AB  - No statistician, social scientist or tarot card reader is needed to attest that
      the gap between the rich and poor in America is increasing. Further, most
      Americans don't care that much about it. There are also more rich people today
      living in the U.S. and there are more people living in poverty. Between 2000 and
      2002, the number of Americans living in poverty increased by nearly 3 million to
      34.6 million. Of these, 12% (or about one half a million persons) are living
      extreme poverty and many are children, with 16.7% likely to be poor (National
      Association of Social Workers, 2003).

PMID- 16418132
TI  - The experience of loneliness of battered old women.
AB  - The present article is part of a larger study examining the life stories of
      battered old women (Buchbinder & Winterstein, 2003; Winterstein, 2002). It is
      based on long in-depth interviews with twenty-one aging women who lived with
      violence for a significant portion of their lives. While the larger study
      examines a broad range of their experience, including loneliness, regret,
      expectations of the future, and an attempt to build a monument to their
      suffering, the present study focuses on loneliness, which appears to constitute
      the central theme of their existential experience. Content analysis of the
      interviews shows that loneliness is experienced on all ecological levels,
      including the self, the family of origin, the violent partner, the children, and
      the extended family. It also permeates the social relationships of the women and
      becomes the predominant motif of their social interactions. The combination of
      loneliness, violence, and old age creates suffering that colors everyday life and
      becomes not only the constant background against which life unfolds but also the
      governing variable in their experience. Their cognitive maps, emotional world,
      and overall sense of self, as well as their sense of existential continuity in
      the world are all affected by loneliness.

PMID- 16418133
TI  - Remarriage in later life: older women's negotiation of power, resources and
      domestic labor.
AB  - Using data from in-depth interviews with 24 community-dwelling women aged 52-90,
      this paper analyzes the remarriage experiences of older women in contrast to
      their first marital relationships. The women's accounts of their experiences in
      their first and later life marriages are examined in terms of the negotiation of
      power, resources, and domestic labor. While first marriages were frequently
      characterized by incompatibility, alcoholism, abuse, and infidelity, second
      marriages were viewed as the marriages the women wished they had had in the first
      place or as relationships that met their later life needs. The women's lived
      experiences are discussed in terms of the changing cultural norms pertaining to
      gender roles, marriage, and divorce.

PMID- 16418134
TI  - Urban black women at midlife: a counseling perspective.
AB  - Increasingly, the scientific community is publishing literature intended to
      conceptualize the experiences of women as they navigate through midlife
      development. Most of that literature is built around a Caucasian norm. In
      contrast, this naturalistic study explores the midlife experiences of Black
      women, some of whom identified as Caribbean emigrants and some as African
      American. An initial focus group of thirteen women met in New York City. Two
      subsequent meetings were each attended by seven of the original thirteen. Data
      were analyzed using a grounded theory approach. Results were compared with those
      of three similar studies: one with rural Caucasian women, one with a group of
      women who identified as Lesbians, and one with a racially mixed group of urban
      women. Counseling implications of shared and differing experiences are discussed.

PMID- 16418135
TI  - Gender differences in retirement decisions in Hong Kong.
AB  - The study of labor force participation at older ages and the process of
      retirement do not have a long tradition in Asia's newly developed societies. This
      study, based on telephone survey of 950 respondents, examines various socio
      economic factors that would influence retirement decision among older workers in
      Hong Kong. The findings show that older men were more likely to participate in
      the labor force than older women. Interestingly, older workers, in particular
      older women, with pension were less likely to retire. Having a working spouse
      decreased the likelihood of retirement and older workers, in particular older
      women, living with married children were more likely to retire. Poor health also
      discourages the propensity to continue working at old age. These findings confirm
      that retirement entails much more than just a decision to stop work, and that
      there were gender differences in retirement decision. Finally, several policy
      challenges, with reference to elderly women, concerning older workers' labor
      force participation were discussed.

PMID- 16418136
TI  - Figuring out whether they can be trusted: older widows' intentions relative to
      hired non-professional home-care helpers.
AB  - The purpose of this phenomenological study was to describe the experience of
      older women relative to trusting hired non-professional home-care helpers. Open
      ended interviews were done about the home-care experience with 25 women over
      three years, and 14 women (age 80-93) shared data about hiring and trusting
      helpers. The women perceived risks to personal safety that adversely influenced
      willingness to seek new helpers. After hiring a helper, the women were still
      trying to discern whether the helper could be trusted. Primary-care providers
      should enable older women to recognize and reduce the risk of having helpers and
      to monitor helpers' behavior, as well as assessing the psychosocial status of
      women who have such helpers.

PMID- 16418138
TI  - Advantages of blood pressure optimization.
AB  - Lowering blood pressure (BP) reduces cardiovascular events, but aggressive BP
      management may not be advantageous. Optimal BP control (target: <120/80 mm Hg)
      and conventional BP control (target: <140/90 mm Hg) were compared in patients
      with hypertension in terms of target-organ damage and tolerability. A total of 23
      patients with hypertension were randomly assigned to optimal versus conventional
      therapy for 6 months. Therapy was initiated with lercanidipine 10 mg/day. For BP
      control, the dose could be doubled or other drugs added. Three indices of target
      organ damage were studied: left ventricular mass (LVM) index, flow-mediated
      dilatation (FMD) of the brachial artery, and 24-hour urinary albumin excretion.
      The BP decreased markedly by 21.3+/-3.4/13.2+/-1.7 mm Hg in the conventional
      therapy group and by 26.6+/-3.6/17.9+/-1.5 mm Hg in the optimal therapy group.
      Diastolic BP was significantly lower, by 4.7+/-2.3 mm Hg, in the optimal therapy
      group (P<.05). Ambulatory BP was also decreased in both groups. There was no
      significant change in LVM or FMD in either group. Baseline LVM index and FMD
      values were correlated with systolic BP (r=0.51, P=.02; r=0.54, P=.009). In the
      optimal therapy group, urinary albumin excretion increased significantly (P=.04).
      Plasma levels of B-type natriuretic peptide (BNP) decreased with antihypertensive
      therapy (P=.03). Treatment was well tolerated, and none of the patients withdrew
      from the study. There was no significant difference in adverse events between the
      2 groups. Optimization of BP is feasible, safe, and well tolerated; however, a
      larger study of longer duration may be needed to demonstrate improvements in LVM
      and endothelial function with conventional versus optimal therapy.

PMID- 16418139
TI  - A pilot study of antitumor effect of gallium ethylenediaminetetramethylene
      phosphonate [Ga(III)-EDTMP] in tumor-bearing rats.
AB  - The inhibitory effects of gallium ethylenediamine-N,N,N',N'-tetrakismethylene
      phosphonate [Ga(III)-EDTMP] was studied on a malignant tumor and metastatic bone
      lesion model induced with Walker carcinosarcoma 256 (WCS 256) in Wistar rats
      weighing 120 to 135 g. A water-soluble chelate, Ga(III)-EDTMP, was prepared for
      injection in a tumor-bearing model. Radiographic analysis at 14 days indicated
      that the bone invasion and osteolysis were markedly reduced in animals treated
      with Ga(III)-EDTMP. The calculated tumor inhibitory rates were 33.16+/-0.38% at a
      dosage of 5 mg/kg and 47.75+/-0.74% at 10 mg/kg. Biochemical markers such as
      serum calcium decreased by 23% (P<.05) and by 31% (P<.01) at dosages of 5 mg/kg
      and 10 mg/kg, respectively, whereas serum alkaline phosphatase (ALPase) activity
      decreased by 47% (P<.01) and 69% (P<.01) at the 2 dosages.

PMID- 16418140
TI  - Can antiemetics really relieve pain?
AB  - The analgesic properties of 2 antiemetic agents--metoclopramide and ondansetron-
      were investigated in studies which showed that metoclopramide may decrease
      postoperative opioid requirements, but the analgesic effect of ondansetron is
      controversial. The postoperative effects of metoclopramide and ondansetron on
      pain in patients undergoing laminectomy were evaluated. Forty six patients were
      randomized into 3 groups: group M, which consisted of 15 patients who received
      intravenous (IV) metoclopramide 0.5 mg 30 minutes before surgery; group O, which
      consisted of 16 patients who received ondansetron IV 0.1 mg 30 minutes before
      surgery; and group C, which consisted of 15 patients who received the same volume
      of saline IV 30 minutes before surgery. The efficacy and duration of analgesia
      were assessed using a visual analogue scale (VAS) at 0, 0.5, 1, 3, 6, and 24
      hours after surgery. Hemodynamic parameters, additional analgesic requirements,
      and adverse effects were recorded for the study groups. Diclofenac 75 mg was
      administered intramuscularly as a rescue analgesic during the postoperative
      period. VAS scores were lower in the metoclopramide group than in the ondansetron
      and control groups (P<.05, each). The patients in the ondansetron and control
      groups required much more diclofenac than the patients in the metoclopramide
      group (P<.05). Metoclopramide administered preoperatively provided postoperative
      analgesia in patients undergoing elective laminectomy.

PMID- 16418141
TI  - Medication adherence and persistence: a comprehensive review.
AB  - Estimates of adherence to long-term medication regimens range from 17% to 80%,
      and nonadherence (or nonpersistence) can lead to increased morbidity, mortality,
      and healthcare costs. Multifaceted interventions that target specific barriers to
      adherence are most effective, because they address the problems and reinforce
      positive behaviors. Providers must assess their patients' understanding of the
      illness and its treatment, communicate the benefits of the treatment, assess
      their patients' readiness to carry out the treatment plan, and discuss any
      barriers or obstacles to adherence that patients may have. A positive,
      supporting, and trusting relationship between patient and provider improves
      adherence. Individual patient factors also affect adherence. For example,
      conditions that impair cognition have a negative impact on adherence. Other
      factors--such as the lack of a support network, limited English proficiency,
      inability to obtain and pay for medications, or severe adverse effects or the
      fear of such effects--are all barriers to adherence. There are multiple reasons
      for nonadherence or nonpersistence; the solution needs to be tailored to the
      individual patient's needs. To have an impact on adherence, healthcare providers
      must understand the barriers to adherence and the methods or tools needed to
      overcome them. This report describes the barriers to medication adherence and
      persistence and interventions that have been used to address them; it also
      identifies interventions and compliance aids that practitioners and organizations
      can implement.

PMID- 16418142
TI  - Incidence of renal insufficiency in cancer patients.
AB  - The frequency of chronic renal insufficiency among cancer patients is unclear.
      The aim of this study was to determine the frequency of impaired renal function
      within a population of cancer patients. One thousand two hundred seventeen
      patients (563 women, 654 men) with cancer underwent serum creatinine
      concentration and glomerular filtration rate (GFR) evaluations. The Cockcroft
      Gault formula was used to estimate the GFR from the creatinine clearance
      (Cl(cr)). Renal insufficiency was defined as a GFR <or=90 mL/min. Among this
      population, 72 (5.9%) demonstrated an abnormal serum creatinine concentration
      (>1.2 mg/dL). According to the Cockcroft-Gault formula evaluations, however, 330
      (27.1%) of the patients had an estimated GFR <90 mL/min. Among these, the Clcr
      was between 60 and 89 mL/min in 241 patients (19.8%); 30 and 59 mL/min in 75
      patients (6.2%); and 15 and 29 mL/min in 7 patients (0.6%); 7 patients (6%) had a
      Cl(cr) <15 mL/min. As a result, 21.2% of patients demonstrating a normal serum
      creatinine level had abnormal renal function. Renal function should be evaluated
      in all cancer patients, regardless of their serum creatinine level, before any
      drug regimen is administered. The Cockcroft-Gault formula appears to be more
      accurate than serum creatinine concentration for diagnosing renal insufficiency
      in patients with cancer, but more prospective studies in this population will be
      necessary to confirm this finding.

PMID- 16418143
TI  - Penile dog bite in an adolescent.
AB  - Dog bites to the external genitalia are rare. In this case, a 16-year-old boy
      suffered a dog bite wound to the penis. The wound was cleansed with copious
      amounts of sterile normal saline by means of high-pressure syringe irrigation.
      The child had an uneventful recovery.

PMID- 16418144
TI  - VEGF-C expression in breast cancer: clinical importance.
AB  - It is well known that angiogenesis and lymphangiogenesis play important roles in
      tumor occurrence and progression. The vascular endothelial growth factor (VEGF)
      family is the most important family of proteins involved in angiogenesis, and
      VEGF-C is the most important molecule in lymphangiogenesis. Lymphangiogenesis
      plays an important role in lymphovascular invasion, metastasis to regional lymph
      nodes, and distant organ metastasis. In this study, the rate of VEGF-C was
      investigated in 217 patients with breast cancer. VEGF-C was evaluated by
      immunohistochemistry and its expression was compared with that of well-known
      prognostic indicators, such as tumor stage and grade, axillary lymph node
      involvement, estrogen and progesterone receptor status, c-erb-B2 expression, and
      extent of lymphovascular invasion. The patient population included 8 men, in
      addition to women before (n=108), during (n=9), and after (n=92) menopause.
      Patients had been diagnosed with invasive ductal (n=181) or invasive lobular
      (n=22) carcinoma, mixed (n=8) or medullary (n=1) carcinoma, or ductal carcinoma
      in situ (n=5). Tumors ranged from stage 0 to IV and grade I to III and the
      distribution of estrogen-positive (n=100) and estrogen-negative (n=110) receptor
      tumors was almost equal. The number of patients with c-erbB2 tumors ranged from
      21 to 49 for each tumor stage, and the number of patients with VEGF-C-negative
      tumors ranged from 28 to 59 for each tumor stage. No important association
      between VEGF-C expression and other prognostic indicators was found. However,
      this may be a result of the lack of standardization among the methods used to
      determine VEGF-C expression. Also, the lymphangiogenic effect may not be overt
      because of the variety of VEGFR-3 variants, which included nonfunctional
      variants. To determine the relationship among angiogenesis, lymphangiogenesis,
      and prognosis, more standardized methods to demonstrate the angiogenesis, and
      prospective studies to cover a larger, more homogenous patient population are
      needed.

PMID- 16418145
TI  - Validation of an overactive bladder awareness tool for use in primary care
      settings.
AB  - Overactive bladder (OAB)--a syndrome characterized by urinary urgency, with or
      without urge incontinence, urinary frequency and nocturia--is estimated to affect
      10% to 20% of the US and European populations. This study was carried out to
      validate a patient-administered screening awareness tool to identify patients
      with bothersome OAB symptoms. Patients were recruited from 12 primary care and 1
      gynecology practice during regularly scheduled appointments. Enrollees completed
      an 8-item questionnaire assessing the amount of "bother" they associated with OAB
      symptoms. Clinicians then asked the patients 4 questions regarding urinary
      frequency, urgency, nocturia, and incontinence. If the screening was positive for
      symptoms of OAB or if the patient provided positive responses to the urinary
      symptom questions, the clinician asked additional questions regarding lifestyle
      and coping behaviors. The clinician then diagnosed the patient, placing him or
      her in the "No OAB," "Possible OAB," or "Probable OAB" category. Multivariable
      logistic regressions controlling for age and sex were performed to assess the
      applicability of the tool for identifying patients with OAB. A total of 1,299
      patients were enrolled, and 1,260 provided complete data. Patients were aged
      51.6+/-17.0 years, 62% were female, most (89%) were Caucasian, 22% experienced
      urinary urgency, and 18% experienced urge incontinence. The prevalence of
      Probable OAB was 12%. The c-index of the model identifying patients with a
      diagnosis of Probable OAB was 0.96, with a sensitivity and specificity of 98.0
      and 82.7. For OAB-V8 scores >or=8, the odds ratio for Probable OAB was 95.7 (95%
      CI: 29.3; 312.4). The OAB-V8 performed well in helping clinicians identify
      patients with bothersome OAB symptoms in a primary care setting and will assist
      clinicians in identifying patients who may benefit from treatment.

PMID- 16418146
TI  - Effectiveness of brachytherapy in the treatment of lip cancer: a retrospective
      study at the istanbul university oncology institute.
AB  - Stage T1 through T3 lip cancers can be treated primarily by brachytherapy (BRTX),
      with or without external radiotherapy (ERT), with adequate safety margins and
      good results. In this study, the outcomes of BRTX were reviewed for patients
      treated at the Brachytherapy Department of the Istanbul University Oncology
      Institute (IUOE). The medical records of 41 patients registered at IUOE with a
      diagnosis of lip cancer between 1988 and 2003 were reviewed. The median follow-up
      time was 88 months (24-160 mo). Among these patients, 21 patients with a primary
      tumor, 14 with tumors arising postoperatively, and 6 with postoperative
      recurrence of tumor were treated using BRTX. A total of 33 patients (80%)
      received BRTX alone and 8 (20%) received BRTX and ERT. The 10-year local control
      rate was 100%, 93%, and 67% for patients treated with BRTX alone, BRTX and
      surgery, and those treated for postoperative recurrence, respectively (P<.02).
      For patients treated with BRTX only and BRTX plus surgery, specific disease-free
      survival was 95% and 94%, respectively, and overall survival was 93% and 100%,
      respectively; these differences were not statistically significant. One patient
      with a postoperative recurrence who had been treated with BRTX died as a result
      of lip cancer. No patients developed any ulcerations, intra-oral complications,
      or mandibular necrosis. In the BRTX only group, 83% had excellent or good
      cosmetic results. In the surgery group, 62% had a contour deformity. In lip
      cancer management, BRTX results were comparable for local control, survival, and
      minimal late effects in normal tissue. This is in accordance with current reports
      in the medical literature. Satisfactory results were observed in patients with
      stage T1 and T2 lesions who had been treated with BRTX only and in patients with
      stage T3 lesions who had been treated with BRTX plus ERT, without a need for
      additional treatment modalities.

PMID- 16418148
TI  - The resistance of Escherichia coli strains isolated from community-acquired
      urinary tract infections.
AB  - Urinary tract infections (UTIs) are the most common infections caused by
      Escherichia coli. Most recent research demonstrates that antibiotic resistance
      has reached a critical point throughout the world, as increased use of
      antibiotics among nonhospitalized patients encourages the growth of drug
      resistant pathogens among that population. The goal of this study was to
      determine the antimicrobial drug resistance of E coli strains isolated from
      community-acquired UTIs in 5 different regions in Turkey. The minimum inhibitory
      concentrations of ciprofloxacin, gentamicin, sulfamethoxazole, trimethoprim,
      trimethoprim-sulfamethoxazole, and ampicillin and for E coli were determined with
      the agar dilution method. Among the 480 strains isolated, 8.3% were resistant to
      ciprofloxacin, 3.3% to gentamicin, 35.4% to sulfamethoxazole, 33.3% to
      trimethoprim, 27.9% to trimethoprim-sulfamethoxazole, and 40.8% to ampicillin.
      These results show that the antibiotics currently most effective against E coli
      are ciprofloxacin and gentamicin. Local epidemiologic trends should be considered
      when prescribing antibacterial therapy. More research in bacterial gene mapping
      will be necessary to elucidate the influence of regional antimicrobial drug use
      and resistance in epidemiologic trends among the general population.

PMID- 16418147
TI  - The role of nebulized inhaled corticosteroid therapy in adult patients with
      asthma and chronic obstructive pulmonary disease.
AB  - Conventional metered-dose inhalers and dry powder inhalers are used by most adult
      patients with asthma and chronic obstructive pulmonary disease who receive
      inhaled corticosteroid therapy. There are circumstances, however, in which
      nebulized inhaled corticosteroid delivery may provide greater clinical benefit to
      these patients. This review discusses the efficacy and safety of nebulized
      inhaled corticosteroid therapy in adult patients with asthma or chronic
      obstructive pulmonary disease for whom nebulized therapy may be preferable.

PMID- 16418149
TI  - Effect of cyproheptadine on serum leptin levels.
AB  - Leptin is a 167 amino acid protein encoded by the obesity gene that is
      synthesized in adipose tissue and interacts with receptors in the hypothalamus
      linked to the regulation of appetite and metabolism. It is known to suppress
      appetite and increase energy expenditure. Cyproheptadine is a piperidine
      antihistamine that increases appetite through its antiserotonergic effect on 5
      HT2 receptors in the brain. Although both leptin and cyproheptadine are effective
      in controlling appetite, their interaction has not been addressed in clinical
      studies. This study evaluated serum leptin concentrations in patients who
      received cyproheptadine to treat a variety of disorders. Sixteen patients aged 7
      to 71 years (mean, 26.25 years) were given cyproheptadine 2 to 6 mg/day for a
      minimum of 7 days. Body weight was measured and blood samples were obtained at
      baseline and after 1 week of treatment. Serum leptin levels were determined by
      leptin radioimmunoassay. The mean body weight at baseline (52.59 kg) did not
      differ significantly from that at 1 week after treatment (52.84 kg; P > .05), but
      the mean leptin level after 1 week of treatment with cyproheptadine (3.14 ng/mL)
      was 14.2% higher than that at baseline (2.75 ng/mL; P < .05). This increase may
      suggest that both leptin and cyproheptadine may affect appetite via similar
      receptors and that cyproheptadine does not impair leptin activity through these
      receptors. Further study will be necessary to clarify this relationship.

PMID- 16418150
TI  - Nonketotic hyperosmolar coma in a patient with type 1 diabetes-related diabetic
      nephropathy: case report.
AB  - Nonketotic hyperosmolar coma (NHC) is characterized by severe hyperglycemia;
      absence of, or only slight ketosis; nonketotic acidosis; severe dehydration;
      depressed sensorium or frank coma; and various neurologic signs. This condition
      is uncommon in type 1 diabetes. Because of little or no osmotic diuresis in
      patients with diabetic nephropathy, increases in plasma osmolality and therefore
      the likelihood of neurologic symptoms are limited. A 20-year-old male patient
      with type 1 diabetes with chronic kidney disease on conservative treatment
      (glomerular filtration rate [GFR], 18 mL/dk) presented with acute nonketotic
      hyperosmolar syndrome. The patient was admitted presenting with thirst, fatigue,
      and drowsiness. Blood biochemistry levels were urea 87 mg/dL, creatinine 5.09
      mg/dL, glucose 830 mg/dL, glycosylated hemoglobin (HbA1c) 8%, C peptide <0.3
      ng/mL, sodium 131 mmol/L, chloride 93 mmol/L, potassium 5.2 mmol/L, and
      calculated serum osmolality 385 mOsm/kg. The presumptive diagnosis on admission
      was nonketotic hyperosmolar syndrome precipitated by urinary infection. This is
      the first case report of hyperosmolar coma in a patient with type 1 diabetes with
      chronic kidney disease.

PMID- 16418151
TI  - Doppler tissue imaging of the heart in secondary amyloidosis.
AB  - Secondary amyloidosis (SA) affects cardiac texture and function by interstitial
      fibrosis. Doppler tissue imaging (DTI) may quantify heart function through the
      assessment of myocardial velocities. Echocardiographic findings of early cardiac
      amyloidosis (CA) without heart failure (HF) caused by SA were determined both by
      standard methods and DTI. It was then determined whether DTI is superior to
      conventional echocardiography in documenting early CA due to SA. Twenty-five
      patients with SA who had CA without HF (group 1) were compared with 25 healthy
      control subjects (group 2). After standard echocardiography, systolic (s), early
      (e) and late diastolic (a) velocities of interventricular septum, anterolateral,
      and anterior and inferior walls were measured from mitral annulus by DTI. The
      averages were called (s(mean)), (e(mean)), and (a(mean)), respectively.
      Fractional shortening (FS) and ejection fraction (EF) values of groups 1 and 2
      were similar. Standard Doppler echocardiographic values were not typical for a
      specific diastolic abnormality. The (s(mean)) and (e(mean)) for group 1 were
      lower but (a(mean)) was higher compared with group 2 (all P < .05). The group 1
      (e(mean)/a(mean)) was lower (P < .0001) and (E/e(mean)) was higher (P = .003)
      than in group 2 (both P < .05). (E/e(mean)) and (E/e(lateral wall)) ratios were
      positively correlated (r = 0.74, P < .05). In patients with early CA due to SA
      without HF, by DTI, (s(mean)) and (e(mean)) velocities decrease and (a(mean))
      velocity increases. These may be markers of subclinical CA of SA when standard
      echocardiography is not informative. (E/e(mean)) ratio may be an alternative
      index to (E/e(lateral wall)).

PMID- 16418152
TI  - Fatal lactic acidosis due to leukemic transformation in a patient with non
      Hodgkin's lymphoma: case report.
AB  - Lactic acidosis (LA) associated with hematologic malignancies is uncommon, life
      threatening, and generally occurs in adults. Its pathogenesis is poorly
      understood. This is a case report of LA due to leukemic transformation that
      occurred in a patient with non-Hodgkin's lymphoma (NHL). A 24-year-old man with
      NHL was admitted to the hospital with dyspnea. Venous blood gas analysis revealed
      metabolic acidosis (pH 7.05; HCO3 6 mEq/L; BE 22 mmol/L; anion gap 28 mEq/L); the
      patient had an elevated plasma lactate concentration (12 mmol/L) and low glucose
      concentration (38 mg/dL). There was no reason other than leukemia-such as
      infection, circulatory failure, or drug use-for the development of severe LA.
      This case report shows that in patients with NHL, leukemic transformation may
      give rise to LA.

PMID- 16418153
TI  - Is external ventricular drainage useful in primary intraventricular hemorrhages?
AB  - Nontraumatic primary intraventricular hemorrhage (PIVH) is characterized by
      direct bleeding into the neuroventricular system. A very rare condition, PIVH
      accounts for 3% of all spontaneous intracerebral hemorrhages. Hypertension is a
      major cause of PIVH. Reports about PIVH in the literature are infrequent and it
      appears to be a relatively benign condition. Between 1998 and 2001, 15 patients
      with PIVH were evaluated in the Departments of Neurosurgery of Yuzuncu Yil and
      Pamukkale Universities; their prognosis and results of treatment with external
      ventricular drainage (EVD) were recorded. The diagnosis was established easily
      and rapidly with computed tomography. Prognoses of the patients were made by the
      Glasgow Coma Score (GCS). Hypertension was the most common etiology (n = 9, 60%);
      the prognosis for survivors (73.3%) was good (mortality, 26.6%). Elderly
      patients, who scored low on the GCS, and patients with coagulopathy had poor
      prognoses. All patients with PIVH underwent surgery with EVD within 24 hours of
      their hospital admission. Applying EVD had positive results and influenced the
      prognosis and early and late complications of PIVH accordingly.

PMID- 16418154
TI  - Patients admitted to the emergency room with upper gastrointestinal bleeding:
      factors influencing recurrence or death.
AB  - The aim of this study was to determine the clinical, laboratory, and endoscopic
      findings that might be related to poor prognoses, such as rebleeding or death, in
      patients admitted to the emergency room with upper gastrointestinal (UGI)
      bleeding. A prospective evaluation was conducted in 99 patients with UGI bleeding
      who were admitted to the emergency room of Hacettepe University Medical School
      between May and December 2001. Twenty-four patients were considered to have a
      poor prognosis. In multivariate analyses, presence of diabetes mellitus or of
      visible vessel at endoscopy, treatment with proton pump inhibitors, and decrease
      in mean blood pressure were found to be independent predictors for poor prognoses
      in this population. Several factors, such as comorbidities, type of treatment, or
      clinical and endoscopic findings, were found to be related to rebleeding or death
      in patients admitted to the emergency room with UGI bleeding necessitating
      intensive care.

PMID- 16418155
TI  - The effectiveness of analgesics in traumatic injuries of the extremities.
AB  - In this study, the effectiveness of different analgesics was investigated in
      patients who presented to the emergency room with traumatic injuries or fractures
      of the extremities. We observed 100 patients (42 male, 58 female) who presented
      to the Konya State Hospital emergency service with isolated traumatic injuries of
      the extremities. We used different analgesics intravenously or intramuscularly in
      those patients with a high or moderate level of pain according to a visual analog
      pain scale. Patient pain levels were assessed 15, 30, and 45 minutes after
      administration of the analgesics. Metamizole sodium 1 g IV was used in 36
      patients and diclofenac sodium 75 mg IM was given to 40 patients; tramadol
      hydrochloride 100 mg IV was administered to 24 patients. Pain became less severe
      after 15 minutes in 92% of patients who received tramadol IV; pain became less
      severe after 30 minutes in 72% of those who received metamizole IV. In contrast,
      pain became less severe after 45 minutes in 65% of patients who received
      diclofenac IM. Tramadol was the most effective analgesic and was also more
      effective earlier than the other analgesics tested.

PMID- 16418156
TI  - Can we use nerve gliding exercises in women with carpal tunnel syndrome?
AB  - This study investigated the effectiveness of nerve gliding exercises used in
      combination with conservative treatment approaches in patients with carpal tunnel
      syndrome. A total of 35 hands of 26 patients with carpal tunnel syndrome were
      divided into 2 groups. Static volar wrist splints were applied to 16 hands in the
      control group, and these patients were trained to modify their functional
      activities in accordance with conservative treatment. In the experimental group,
      nerve gliding exercises were applied to 19 hands that were also treated
      conservatively. A day-and-night splint, together with the conservative training
      program, was applied for 6 weeks to both groups. Subsequently, a night splint
      only was used in both groups, and nerve gliding exercises were continued in the
      experimental group for the remaining 4 weeks. Pretreatment and posttreatment
      assessments of pain, sensation, muscle strength, and grip and pinch strength,
      along with Tinel and Phalen tests, were performed in all cases;
      electrophysiologic measurements were recorded. Significant progress was detected
      in both control and experimental groups during the posttreatment phase compared
      with the initial phase (P < .05). However, when the 2 groups were compared, the
      experimental group in which nerve gliding exercises were added to conservative
      therapy approaches demonstrated more rapid pain reduction; these patients also
      showed greater functional improvement, especially in grip strength (P < .05).

PMID- 16418157
TI  - Rotavirus gastroenteritis.
AB  - Rotavirus is the single most important cause of severe, dehydrating
      gastroenteritis in infants and young children worldwide. Rotavirus
      gastroenteritis is associated with high morbidity in developed countries and
      significant mortality in developing countries. Virtually all children are
      infected with rotavirus by 3 years of age. Fecal-oral transmission is the most
      likely route of virus spread. Group A serotype strains G1 through G4 account for
      more than 90% of rotavirus gastroenteritis in humans, with G1 being the
      predominant serotype. The virus preferentially infects the mature small
      intestinal enterocytes. Rotavirus gastroenteritis is characterized by fever,
      vomiting, and diarrhea, with vomiting particularly prominent. Dehydration is a
      frequent complication because of the severity of the diarrhea and the associated
      vomiting. Rehydration and maintenance of proper fluid and electrolyte balance
      remain the mainstay of treatment. Hygienic measures have little effect on the
      reduction of rotavirus infection rates. The disease can be effectively controlled
      by universal rotavirus vaccination.

PMID- 16418158
TI  - Intrapatient symptom variability in adults and children with asthma: results of a
      survey.
AB  - The objective of this survey was to evaluate variability of symptoms in adult and
      pediatric patients with persistent asthma. Prospective participants from a US
      database of patients with asthma were invited to complete an Internet-based
      survey designed to assess the occurrence of asthma symptoms during the past year.
      A total of 1311 adult patients and 491 caregivers of pediatric patients were
      surveyed. Adult patients (18%-30%) and pediatric patients (8%-20%) experienced a
      variety of symptoms on a daily basis. At least 50% of patients receiving
      treatment experienced variability in 1 or more symptoms during the previous year.
      The most common treatment recommendation when asthma symptoms were experienced
      included changing the number of medication (reliever or controller) inhalations
      (48% and 55% of adult and pediatric patients, respectively) or adding another
      medication (31% and 39%). This survey indicates that adult patients and
      caregivers of pediatric patients report variability in asthma symptoms over time,
      even when asthma medications are taken.

PMID- 16418159
TI  - Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD:
      a multicenter, randomized prospective study.
AB  - This community-based study was designed to evaluate treatment outcomes with OROS
      methylphenidate (MPH) and atomoxetine in children with
      attentiondeficit/hyperactivity disorder (ADHD), as assessed by physicians and
      parents in a setting that resembles clinical practice. In a multicenter,
      prospective, open-label study, children 6 to 12 years of age with ADHD were
      randomized (2:1, respectively) to 3 weeks of treatment with once-daily OROS MPH
      or atomoxetine. Investigatorrated measures of symptoms included the ADHD Rating
      Scale (ADHD-RS) and the Clinical Global Impression-Improvement of Illness scale
      (CGI-I). Assessments were made at baseline and during a telephone interview in
      week 1, a clinic visit in week 2, and a final clinic visit in week 3. In total,
      1323 patients received OROS MPH (n = 850) or atomoxetine (n = 473). Significant
      reductions from baseline in investigator-evaluated ADHD-RS scores were observed
      among patients receiving OROS MPH and those receiving atomoxetine. At the end of
      the study, mean decreases from baseline ADHD-RS scores were 20.24 for OROS MPH
      and 16 for atomoxetine (P < .001). Between-treatment differences appeared to
      increase over time (2.77, 3.44, and 4.24 at weeks 1, 2, and 3, respectively; P <
      .001). Treatment response (ie, 25% reduction from baseline ADHD-RS scores) was
      significantly greater at each evaluation for patients taking OROS MPH than for
      those taking atomoxetine (P < .001). Similar percentages of patients taking OROS
      MPH (4.8%) and atomoxetine (5.5%) withdrew because of adverse events. Although
      community-based studies often lack the control of randomized, placebo-controlled
      trials, these results nevertheless suggest greater ADHD symptom improvement with
      OROS MPH compared with atomoxetine.

PMID- 16418160
TI  - Postmarketing surveillance study of nateglinide in Japan.
AB  - Nateglinide is an oral antidiabetic medication that acts through rapid, short
      term stimulation of insulin production. This study was undertaken to identify the
      incidence and nature of adverse effects of nateglinide and to assess its efficacy
      in clinical practice. Patients (n = 3254) were recruited from 606 centers in
      Japan with a 12-week observation period. Pretreatment and posttreatment values
      were obtained for fasting blood glucose, postprandial blood glucose, hemoglobin
      A1c (HbA1c), triglycerides, cholesterol, and body mass index. All adverse events
      were reported, along with standard laboratory blood variables. The incidence of
      adverse events was 7.40%; hypoglycemia, including hypoglycemic symptoms, was
      reported as the most prevalent (1.62%). Adverse events were observed more
      frequently in patients with hepatic or renal dysfunction; no significant findings
      were noted in the remaining patient population. The efficacy rating determined by
      the treating physicians was 76.40%. HbA1c decreased by 0.81% from 7.70+/-1.53% to
      6.89+/-1.22%, postprandial glucose decreased by 54.05 mg/dL from 228.91+/-73.69
      mg/dL to 174.86+/-62.86 mg/dL, and fasting glucose decreased by 23.73 mg/dL from
      164.15+/-51.42 mg/dL to 140.43+/-42.63 mg/dL. These effects were most marked in
      patients who were previously medication naive or who had been diagnosed with
      diabetes for a short period. Mean body mass index decreased, and nateglinide was
      equally effective in obese patients. Nateglinide showed good therapeutic effect
      when used as the first choice in patients with a short duration of diabetes, and
      in those with no history of previous treatment. Moreover, nateglinide seemed to
      be useful for the treatment of elderly patients and obese patients.

PMID- 16418161
TI  - Cutaneous burns treated with hydrogel (Burnshield) and a semipermeable adhesive
      film.
AB  - HYPOTHESIS: A transparent adhesive film possessing selective permeability
      combined with a hydrogel (Burnshield) may be effective in burn patients to reduce
      skin maceration, improve medication, control pain more effectively, and reduce
      the incidence of late complications (hypertrophic scars). DESIGN: This is a
      prospective study; the mean follow-up in all patients was 28.4 months (range, 14
      35 months). The external part of the film is impermeable to fluid and
      microorganisms, but allows transpiration of water vapor from the cutis. The
      permeability to water vapor of a semipermeable film in contact with liquids is
      measured in grams per meters squared every 24 hours at 37 degrees C, and is
      defined as the moisture vapor transmission rate. In this study, a film with a
      moisture vapor transmission rate of 1600 g/m(2) every 24 hours at 37 degrees C
      was used. PATIENTS: For about 2 years, this type of therapy was used in the first
      aid treatment of 48 burn patients, 4 of whom were lost during therapy and 4 of
      whom were unavailable for follow-up. INTERVENTIONS: The patients were treated
      with hydrogel and a semipermeable film at first medication, and some were treated
      in this way during subsequent medications. MAIN OUTCOME MEASURES: The mean
      reepithelialization time of all patients was 17 days (range, 4-60 days); 8 (20%)
      of 40 patients with complications were treated with a gel (Same Plast Gel). Late
      complications were observed: hypertrophic scars in 2 patients (5%) and dyschromic
      lesions in 6 (15%). RESULTS: The most frequent complication, which occurred at
      various stages during medication, was skin maceration (15 [34%] of 44 patients).
      Other complications recorded during therapy were infections in 2 patients (5%),
      vertigo in 1 patient (2%), and abundant fibrin production in 1 patient (2%). In
      some of the patients, associated diseases and/or conditions were found: hepatic
      cirrhosis, diabetes mellitus, epilepsy, and pregnancy (33rd week) (each found in
      1 patient each). Four patients were sent to the burn unit, 3 with second-degree
      burns of the hand and 1 with first-/second-degree burns of the abdomen and thigh,
      with 12% of the total body surface area burned. CONCLUSIONS: In the
      reepithelialization phase, complications were recorded in 8 of the 40 patients: 7
      (18%) had residual inflammation and 1 (2%) had a hypertrophic scar. During the
      follow-up, late complications were recorded in 2 (5%) of the 40 patients. A gel
      was used in 8 patients: in 6 of the 7 patients with residual inflammation, the
      complication resolved, while in 1, despite therapy, the residual inflammation
      evolved into hypertrophic scarring. Treatment with the gel in the 2 patients with
      late lesions reduced the thickness and extent of the lesions, with minimal
      aesthetic and functional damage.

PMID- 16418162
TI  - Fatty acid amide hydrolase determines anandamide-induced cell death in the liver.
AB  - The endocannabinoid anandamide (AEA) induces cell death in many cell types, but
      determinants of AEA-induced cell death remain unknown. In this study, we
      investigated the role of the AEA-degrading enzyme fatty acid amide hydrolase
      (FAAH) in AEA-induced cell death in the liver. Primary hepatocytes expressed high
      levels of FAAH and were completely resistant to AEA-induced cell death, whereas
      primary hepatic stellate cells (HSCs) expressed low levels of FAAH and were
      highly sensitive to AEA-induced cell death. Hepatocytes that were pretreated or
      with the FAAH inhibitor URB597 isolated from FAAH(-/-) mice displayed increased
      AEA-induced reactive oxygen species (ROS) formation and were susceptible to AEA
      mediated death. Conversely, overexpression of FAAH in HSCs prevented AEA-induced
      death. Since FAAH inhibition conferred only partial AEA sensitivity in
      hepatocytes, we analyzed additional factors that might regulate AEA-induced
      death. Hepatocytes contained significantly higher levels of glutathione (GSH)
      than HSCs. Glutathione depletion by dl-buthionine-(S,R)-sulfoximine rendered
      hepatocytes susceptible to AEA-mediated ROS production and cell death, whereas
      GSH ethyl ester prevented ROS production and cell death in HSCs. FAAH inhibition
      and GSH depletion had additive effects on AEA-mediated hepatocyte cell death
      resulting in almost 70% death after 24 h at 50 microm AEA and lowering the
      threshold for cell death to 500 nm. Following bile duct ligation, FAAH(-/-) mice
      displayed increased hepatocellular injury, suggesting that FAAH protects
      hepatocytes from AEA-induced cell death in vivo. In conclusion, FAAH and GSH are
      determinants of AEA-mediated cell death in the liver.

PMID- 16418163
TI  - Molecular cloning and characterization of UDP-glucose dehydrogenase from the
      amphibian Xenopus laevis and its involvement in hyaluronan synthesis.
AB  - UDP-glucose dehydrogenase (UGDH) supplies the cell with UDP-glucuronic acid (UDP
      GlcUA), a precursor of glycosaminoglycan and proteoglycan synthesis. Here we
      reported the cloning and the characterization of the UGDH from the amphibian
      Xenopus laevis that is one of the model organisms for developmental biology. We
      found that X. laevis UGDH (xUGDH) maintained a very high degree of similarity
      with other known UGDH sequences both at the genomic and the protein levels. Also
      its kinetic parameters are similar to those of UGDH from other species. During X.
      laevis development, UDGH is always expressed but clearly increases its mRNA
      levels at the tail bud stage (i.e. 30 h post-fertilization). This result fits
      well with our previous observation that hyaluronan, a glycosaminoglycan that is
      synthesized using UDP-GlcUA and UDP-N-acetylglucosamine, is abundantly detected
      at this developmental stage. The expression of UGDH was found to be related to
      hyaluronan synthesis. In human smooth muscle cells the overexpression of xUGDH or
      endogenous abrogation of UGDH modulated hyaluronan synthesis specifically. Our
      findings were confirmed by in vivo experiments where the silencing of xUGDH in X.
      laevis embryos decreased glycosaminoglycan synthesis causing severe embryonic
      malformations because of a defective gastrulation process.

PMID- 16418164
TI  - Novel carbohydrate-binding activity of pancreatic trypsins to N-linked glycans of
      glycoproteins.
AB  - How glycosylation affects the reactivity of proteins to trypsin is not well
      understood. Bovine and porcine pancreatic trypsins were discovered to bind to
      alpha-Man, Neu5Acalpha2,6Galbeta1,4Glc, and alpha-galactose sequences by binding
      studies with biotinylated sugar-polymers. Quantitative kinetic studies supported
      that phenylmethylsulfonyl fluoride (PMSF)-treated trypsin binds to glycolipid
      analogues possessing alpha-Man or alpha-NeuAc but not to those possessing beta
      galactose or beta-GlcNAc residue. Enzyme-linked immunosorbent assay (ELISA)
      showed that trypsin binds to six kinds of biotinylated glycoproteins possessing
      high mannose-type and complex-type N-glycans but not to bovine submaxillary
      mucin, which possesses only O-glycans. Further, the binding of trypsin to
      glycoproteins was differentially changed by treatments with sequential
      exoglycosidases, endoglycosidase H, or N-glycosidase F. Quantitative kinetic
      studies indicated that PMSF-treated trypsin binds with bovine thyroglobulin with
      the affinity constant of 10(10) m(-1), which was the highest among the
      glycoproteins examined, and that alpha-galactosidase treatment decreased it to
      10(5) m(-1). PMSF-treated trypsin bound to other glycoproteins, including
      ovomucoid, a trypsin inhibitor, with the affinity constants of 10(8)-10(5) mol(
      1) and were markedly changed by glycosidase treatments in manners consistent with
      the sugar-binding specificities suggested by ELISA. Thus, the binding site for
      glycans was shown to be distinct from the catalytic site, allowing trypsin to
      function as an uncompetitive activator in the hydrolysis of a synthetic peptide
      substrate. Correspondingly the carbohydrate-binding activities of trypsin were
      unaffected by treatment with PMSF or soybean trypsin inhibitor. The results
      indicate the presence of an allosteric regulatory site on trypsin that sugar
      specifically interacts with glycoproteins in addition to the proteolytic
      catalytic site.

PMID- 16418165
TI  - The Saccharomyces cerevisiae proteome of oxidized protein thiols: contrasted
      functions for the thioredoxin and glutathione pathways.
AB  - Protein thiol oxidation subserves important biological functions and constitutes
      a sequel of reactive oxygen species toxicity. We developed two distinct thiol
      labeling approaches to identify oxidized cytoplasmic protein thiols in
      Saccharomyces cerevisiae. Inone approach, we used N-(6-(biotinamido)hexyl)-3'-(2'
      pyridyldithio)-propionamide to purify oxidized protein thiols, and in the other,
      we used N-[(14)C]ethylmaleimide to quantify this oxidation. Both approaches
      showed a large number of the same proteins with oxidized thiols ( approximately
      200), 64 of which were identified by mass spectrometry. We show that,
      irrespective of its mechanism, protein thiol oxidation is dependent upon
      molecular O(2). We also show that H(2)O(2) does not cause de novo protein thiol
      oxidation, but rather increases the oxidation state of a select group of
      proteins. Furthermore, our study reveals contrasted differences in the oxidized
      proteome of cells upon inactivation of the thioredoxin or GSH pathway suggestive
      of very distinct thiol redox control functions, assigning an exclusive role for
      thioredoxin in H(2)O(2) metabolism and the presumed thiol redox buffer function
      for GSH. Taken together, these results suggest the high selectivity of
      cytoplasmic protein thiol oxidation.

PMID- 16418166
TI  - Significant redox insensitivity of the functions of the SARS-CoV spike
      glycoprotein: comparison with HIV envelope.
AB  - The capacity of the surface glycoproteins of enveloped viruses to mediate
      virus/cell binding and membrane fusion requires a proper thiol/disulfide balance.
      Chemical manipulation of their redox state using reducing agents or free
      sulfhydryl reagents affects virus/cell interaction. Conversely, natural
      thiol/disulfide rearrangements often occur during the cell interaction to trigger
      fusogenicity, hence the virus entry. We examined the relationship between the
      redox state of the 20 cysteine residues of the SARS-CoV (severe acute respiratory
      syndrome coronavirus) Spike glycoprotein S1 subdomain and its functional
      properties. Mature S1 exhibited approximately 4 unpaired cysteines, and
      chemically reduced S1 displaying up to approximately 6 additional unpaired
      cysteines still bound ACE2 and enabled fusion. In addition, virus/cell membrane
      fusion occurred in the presence of sulfhydryl-blocking reagents and
      oxidoreductase inhibitors. Thus, in contrast to various viruses including HIV
      (human immunodeficiency virus) examined in parallel, the functions of the SARS
      CoV Spike glycoprotein exhibit a significant and surprising independence of redox
      state, which may contribute to the wide host range of the virus. These data
      suggest clues for molecularly engineering vaccine immunogens.

PMID- 16418167
TI  - The Bacillus subtilis YkuV is a thiol:disulfide oxidoreductase revealed by its
      redox structures and activity.
AB  - The Bacillus subtilis YkuV responds to environmental oxidative stress and plays
      an important role for the bacteria to adapt to the environment. Bioinformatic
      analysis suggests that YkuV is a homolog of membrane-anchored proteins and
      belongs to the thioredoxin-like protein superfamily containing the typical Cys
      Xaa-Xaa-Cys active motif. However, the biological function of this protein
      remains unknown thus far. In order to elucidate the biological function, we have
      determined the solution structures of both the oxidized and reduced forms of B.
      subtilis YkuV by NMR spectroscopy and performed biochemical studies. Our results
      demonstrated that the reduced YkuV has a low midpoint redox potential, allowing
      it to reduce a variety of protein substrates. The overall structures of both
      oxidized and reduced forms are similar, with a typical thioredoxin-like fold.
      However, significant conformational changes in the Cys-Xaa-Xaa-Cys active motif
      of the tertiary structures are observed between the two forms. In addition, the
      backbone dynamics provide further insights in understanding the strong redox
      potential of the reduced YkuV. Furthermore, we demonstrated that YkuV is able to
      reduce different protein substrates in vitro. Together, our results clearly
      established that YkuV may function as a general thiol:disulfide oxidoreductase,
      which acts as an alternative for thioredoxin or thioredoxin reductase to maintain
      the reducing environment in the cell cytoplasm.

PMID- 16418168
TI  - Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten)
      mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross
      talk between stress signaling and insulin signaling in resistin-treated human
      endothelial cells.
AB  - The key feature of metabolic syndrome, a cluster of metabolic and cardiovascular
      disorders, is systemic insulin resistance, which is associated with dysregulated
      endothelial nitric-oxide synthase (eNOS). Stress signaling induced by
      inflammation can inhibit insulin signaling. However, molecular mechanisms for the
      cross-talk between stress signaling and insulin resistance are only partially
      understood. Resistin, an adipokine/cytokine, is involved in inflammatory
      processes that could lead to insulin resistance status and vascular diseases. In
      the current study, we observed that resistin inhibited insulin signaling and eNOS
      activation in endothelial cells. Up-regulation of PTEN (phosphatase and tensin
      homolog deleted on chromosome ten) expression by resistin may mediate the
      inhibitory effects. Activated stress signaling p38 MAPK, but not JNK, is involved
      in PTEN up-regulation. We further found that p38 target transcriptional factor
      activating transcription factor-2 (ATF-2) bound to ATF sites in the PTEN
      promoter. The phosphorylation/activation of ATF-2 and its binding to PTEN
      promoter were increased by resistin treatment. In summary, up-regulation of PTEN
      is involved in the inhibitory effects of resistin on insulin signaling and eNOS
      activation in endothelial cells. Resistin induces PTEN expression by activating
      stress signaling p38 pathway, which may activate target transcription factor ATF
      2, which in turn induces PTEN expression. Our findings suggest that resistin
      mediated inhibition of insulin signaling and eNOS activation may contribute to
      cardiovascular diseases.

PMID- 16418169
TI  - Genome-wide transcriptional profile of Escherichia coli in response to high
      levels of the second messenger 3',5'-cyclic diguanylic acid.
AB  - Cyclic diguanylic acid (c-di-GMP; cGpGp) is a global second messenger controlling
      motility and adhesion in bacterial cells. Intracellular concentrations of c-di
      GMP depend on two opposite activities: diguanylate cyclase, recently assigned to
      the widespread GGDEF domain, and c-di-GMP-specific phosphodiesterase, associated
      with proteins harboring the EAL domain. To date, little is known about the
      targets of c-di-GMP in the cell or if it affects transcriptional regulation of
      certain genes. In order to expand our knowledge of the effect of this molecule on
      the bacterial metabolism, here we report on the Escherichia coli transcriptional
      profile under high levels of c-di-GMP. We show that an important number of genes
      encoding cell surface and membrane-bound proteins are altered in their
      transcriptional activity. On the other hand, genes encoding several
      transcriptional factors, such as Fur, RcsA, SoxS, and ZraR, are up-regulated, and
      others, such as GadE, GadX, GcvA, and MetR, are down-regulated. Transcription of
      motility and cell division genes were altered, and consistent with this was the
      physiological analysis of cells overexpressing yddV, a diguanylate cyclase; these
      cells displayed an abnormal cell division process when high levels of c-di-GMP
      were present. We also show evidence that the diguanylate cyclase gene yddV is co
      transcribed with dos, a heme base oxygen sensor with c-di-GMP-specific
      phosphodiesterase activity. A delta dos::kan mutation rendered the cells unable
      to divide properly, suggesting that dos and yddV may be part of a fine-tuning
      mechanism for regulating the intracellular levels of c-di-GMP.

PMID- 16418170
TI  - The molecular circuitry regulating the switch between iron deficiency and
      overload in mice.
AB  - Recent positional cloning of the radiation-induced polycythaemia (Pcm) mutation
      revealed a 58-bp microdeletion in the promoter region of ferroportin 1 (Fpn1),
      the sole cellular iron exporter identified to date. Here we report a molecular
      definition of the regulatory mechanisms governing the dynamic changes in iron
      balance in Pcm heterozygous mice between 3 and 12 weeks of age. Hepatic and/or
      duodenal response patterns of iron metabolism genes, such as Trfr, cybrd1, and
      Slc11a2, explained the transition from early postnatal iron deficiency to iron
      overload by 12 weeks of age. A significant delay in developmental up-regulation
      of hepcidin (Hamp), the pivotal hormonal regulator of iron homeostasis,
      correlated with high levels of Fpn1 expression in hepatic Kupffer cells and
      duodenal epithelial cells at 7 weeks of age. Conversely, upon up-regulation of
      Hamp expression at 12 weeks of age, Fpn1 expression decreased, indicative of a
      Hamp-mediated homeostatic loop. Hamp regulation due to iron did not appear
      dependent on transcription-level changes of the murine homolog of Hemojuvelin
      (Rgmc). Aged cohorts of Pcm mice exhibited low levels of Fpn1 expression in the
      context of an iron-deficient erythropoiesis and profound iron sequestration in
      reticuloendothelial macrophages, duodenum, and other tissues. Thus, similar to
      the anemia of chronic disease, these findings demonstrate decreased iron
      bioavailability due to sustained down-regulation of Fpn1 levels by Hamp. We
      conclude that regulatory alleles, such as Pcm, with highly dynamic changes in
      iron balance are ideally suited to interrogate the genetic circuitry regulating
      iron metabolism.

PMID- 16418171
TI  - Direct cross-talk of interleukin-6 and insulin signal transduction via insulin
      receptor substrate-1 in skeletal muscle cells.
AB  - The exercise-induced interleukin (IL)-6 production and secretion within skeletal
      muscle fibers has raised the question of a putative tissue-specific function of
      IL-6 in the energy metabolism of the muscle during and after the exercise. In the
      present study, we followed the hypothesis that IL-6 signaling may directly
      interact with insulin receptor substrate (IRS)-1, a keystone in the insulin
      signaling cascade. We showed that IL-6 induces a rapid recruitment of IRS-1 to
      the IL-6 receptor complex in cultured skeletal muscle cells. Moreover, IL-6
      induced a rapid and transient phosphorylation of Ser-318 of IRS-1 in muscle cells
      and in muscle tissue, but not in the liver of IL-6-treated mice, probably via the
      IL-6-induced co-recruitment of protein kinase C-delta. This Ser-318
      phosphorylation improved insulin-stimulated Akt phosphorylation and glucose
      uptake in myotubes since transfection with an IRS-1/Glu-318 mutant simulating a
      permanent phospho-Ser-318 modification increased Akt phosphorylation and glucose
      uptake. Noteworthily, two inhibitory mechanisms of IL-6 on insulin action,
      phosphorylation of the inhibitory Ser-307 residue of IRS-1 and induction of SOCS
      3 expression, were only found in liver but not in muscle of IL-6-treated mice.
      Thus, the data provided evidence for a possible molecular mechanism of the
      physiological metabolic effects of IL-6 in skeletal muscle, thereby exerting
      short term beneficial effects on insulin action.

PMID- 16418172
TI  - Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes.
AB  - To comprehend the Ras/ERK MAPK cascade, which comprises Ras, Raf, MEK, and ERK,
      several kinetic simulation models have been developed. However, a large number of
      parameters that are essential for the development of these models are still
      missing and need to be set arbitrarily. Here, we aimed at collecting these
      missing parameters using fluorescent probes. First, the levels of the signaling
      molecules were quantitated. Second, to monitor both the activation and nuclear
      translocation of ERK, we developed probes based on the principle of fluorescence
      resonance energy transfer. Third, the dissociation constants of Ras.Raf, Raf.MEK,
      and MEK.ERK complexes were estimated using a fluorescent tag that can be
      highlighted very rapidly. Finally, the same fluorescent tag was used to measure
      the nucleocytoplasmic shuttling rates of ERK and MEK. Using these parameters, we
      developed a kinetic simulation model consisting of the minimum essential members
      of the Ras/ERK MAPK cascade. This simple model reproduced essential features of
      the observed activation and nuclear translocation of ERK. In this model, the
      concentration of Raf significantly affected the levels of phospho-MEK and phospho
      ERK upon stimulation. This prediction was confirmed experimentally by decreasing
      the level of Raf using the small interfering RNA technique. This observation
      verified the usefulness of the parameters collected in this study.

PMID- 16418173
TI  - Identification of the mstE gene encoding a glucose-inducible, low affinity
      glucose transporter in Aspergillus nidulans.
AB  - The mstE gene encoding a low affinity glucose transporter active during the
      germination of Aspergillus nidulans conidia on glucose medium has been
      identified. mstE expression also occurs in hyphae, is induced in the presence of
      other repressing carbon sources besides glucose, and is dependent on the function
      of the transcriptional repressor CreA. The expression of MstE and its subcellular
      distribution have been studied using a MstE-sGFP fusion protein. Concordant with
      data on mstE expression, MstE-sGFP is synthesized in the presence of repressing
      carbon sources, and fluorescence at the periphery of conidia and hyphae is
      consistent with MstE location in the plasma membrane. Deletion of mstE has no
      morphological phenotype but results in the absence of low affinity glucose uptake
      kinetics, the latter being substituted by a high affinity system.

PMID- 16418174
TI  - The affinity of a major Ca2+ binding site on GRP78 is differentially enhanced by
      ADP and ATP.
AB  - GRP78 is a major protein regulated by the mammalian endoplasmic reticulum stress
      response, and up-regulation has been shown to be important in protecting cells
      from challenge with cytotoxic agents. GRP78 has ATPase activity, acts as a
      chaperone, and interacts specifically with other proteins, such as caspases, as
      part of a mechanism regulating apoptosis. GRP78 is also reported to have a
      possible role as a Ca2+ storage protein. In order to understand the potential
      biological effects of Ca2+ and ATP/ADP binding on the biology of GRP78, we have
      determined its ligand binding properties. We show here for the first time that
      GRP78 can bind Ca2+, ATP, and ADP, each with a 1:1 stoichiometry, and that the
      binding of cation and nucleotide is cooperative. These observations do not
      support the hypothesis that GRP78 is a dynamic Ca2+ storage protein. Furthermore,
      we demonstrate that whereas Mg2+ enhances GRP78 binding to ADP and ATP to the
      same extent, Ca2+ shows a differential enhancement. In the presence of Ca2+, the
      KD for ATP is lowered approximately 11-fold, and the KD for ADP is lowered around
      930-fold. The KD for Ca2+ is lowered approximately 40-fold in the presence of ATP
      and around 880-fold with ADP. These findings may explain the biological
      requirement for a nucleotide exchange factor to remove ADP from GRP78. Taken
      together, our data suggest that the Ca2+-binding property of GRP78 may be part of
      a signal transduction pathway that modulates complex interactions between GRP78,
      ATP/ADP, secretory proteins, and caspases, and this ultimately has important
      consequences for cell viability.

PMID- 16418175
TI  - The PnrA (Tp0319; TmpC) lipoprotein represents a new family of bacterial purine
      nucleoside receptor encoded within an ATP-binding cassette (ABC)-like operon in
      Treponema pallidum.
AB  - Treponema pallidum, the bacterial agent of syphilis, cannot be cultivated in
      vitro. This constraint has severely impeded the study of the membrane biology of
      this complex human pathogen. A structure-to-function approach thus was adopted as
      a means of discerning the likely function of Tp0319, a 35-kDa cytoplasmic
      membrane-associated lipoprotein of T. pallidum formerly designated as TmpC. A 1.7
      A crystal structure showed that recombinant Tp0319 (rTp0319) consists of two
      alpha/beta domains, linked by three crossovers, with a deep cleft between them
      akin to ATP-binding cassette (ABC) receptors. In the cleft, a molecule of inosine
      was bound. Isothermal titration calorimetry demonstrated that rTp0319
      specifically binds purine nucleosides (dissociation constant (Kd) approximately
      10(-7) M). This predilection for purine nucleosides by rTp0319 is consistent with
      its likely role as a receptor component of a cytoplasmic membrane-associated
      transporter system. Reverse transcription-PCR analysis of RNA isolated from
      rabbit tissue-extracted T. pallidum additionally showed that tp0319 is
      transcriptionally linked to four other downstream open reading frames, thereby
      supporting the existence of an ABC-like operon (tp0319-0323). We herein thus re
      name tp0319 as purine nucleoside receptor A (pnrA), with its operonic partners
      tp0320-0323 designated as pnrB-E, respectively. Our study not only infers that
      PnrA transports purine nucleosides essential for the survival of T. pallidum
      within its obligate human host, but to our knowledge, this is the first
      description of an ABC-type nucleoside transport system in any bacterium. PnrA has
      been grouped with a functionally uncharacterized protein family (HBG016869),
      thereby implying that other members of the family may have similar nucleoside
      binding function(s).

PMID- 16418176
TI  - Inhibition of chemically induced skin carcinogenesis by sulindac is independent
      of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta).
AB  - Inhibition of cyclooxygenase-2 (COX2) by non-steroidal anti-inflammatory drugs
      (NSAID) is known to suppress skin carcinogenesis. It was further suggested that
      inhibition of COX2-derived prostaglandins by NSAIDs could reduce levels of
      putative endogenous ligands of peroxisome proliferator-activated receptor-beta
      (PPARbeta), and these ligands could potentiate tumorigenesis. However, it is
      currently unclear whether ligand activation of PPARbeta either inhibits or
      potentiates carcinogenesis. The present studies were designed to examine the
      mechanism of NSAID-mediated chemoprevention in skin, and, in particular, to
      determine the role of PPARbeta in this process. A two-stage skin carcinogenicity
      bioassay was performed using wild-type and PPARbeta-null mice that were fed
      either a control diet or one containing 0.32 g sulindac/kg diet. Significant
      inhibition of chemically induced skin carcinogenesis was observed in both wild
      type and PPARbeta-null mice, and this was associated with a marked decrease in
      the concentration of skin prostaglandins including PGE(2) and PGI(2). Results
      from these studies demonstrate that inhibition of COX2 by dietary sulindac in
      mouse skin can effectively inhibit chemically induced skin carcinogenesis, and
      suggest that the mechanism underlying this chemopreventive effect is independent
      of PPARbeta. Additionally, results from these studies do not support the
      hypothesis that ligand activation of PPARbeta by COX-derived metabolites
      potentiates chemically induced skin carcinogenesis.

PMID- 16418177
TI  - Beta-carotene breakdown products enhance genotoxic effects of oxidative stress in
      primary rat hepatocytes.
AB  - Since it has to be expected that individuals exposed to oxidative stress who take
      supplements of beta-carotene are simultaneously exposed to both beta-carotene
      cleavage products (CPs) and oxidative stress, and both exposures have been
      demonstrated to cause genotoxic effects in primary rat hepatocytes, cyto- and
      genotoxic effects on primary rat hepatocytes after supplementation of the medium
      with increasing concentrations of a CP mixture during exposure to oxidative
      stress by treatment with either DMNQ (2,3-dimethoxy-1,4-naphthoquinone) or
      hypoxia/reoxygenation (Hy/Reox) was investigated. The cytological endpoints
      analysed were the mitotic indices, the percentages of apoptotic and necrotic
      cells, the percentages of micronucleated (MN) cells and the number of chromosomal
      aberrations (CAs) and sister chromatid exchanges (SCE). The results obtained
      clearly demonstrate that the CP mixture enhances the genotoxic effects of
      oxidative stress exposure, whereas it had no effect at all on the endpoints of
      cytotoxicity studied. These results further support the hypothesis that CP might
      be responsible for the reported carcinogenic response in the beta-CArotene and
      Retinol Efficacy Trial (CARET) and Alpha-Tocopherol Beta-carotene Cancer
      prevention (ATBC) chemoprevention trials.

PMID- 16418178
TI  - Synergistic action of brain-derived neurotrophic factor and lens injury promotes
      retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo.
AB  - Trauma or disease in the CNS often leads to neuronal death and consequent loss of
      functional connections. The idea has been put forward that strategies aimed at
      repairing the injured CNS involve stimulation of both neuronal survival and axon
      regeneration. We tested this hypothesis in the adult rat retinocollicular system
      by combining two strategies: (i) exogenous administration of brain-derived
      neurotrophic factor (BDNF), a potent survival factor for damaged retinal ganglion
      cells (RGCs) and (ii) lens injury, which promotes robust growth of transected RGC
      axons. Our results demonstrate that BDNF and lens injury interact synergistically
      to promote neuronal survival: 71% of RGCs were alive at 2 weeks after optic nerve
      injury, a time when only approximately 10% of these neurons remain without
      treatment. Intravitreal injection of BDNF, however, led to regeneration failure
      following lens injury. The effect of BDNF could not be generalized to other
      growth factors, as ciliary neurotrophic factor did not cause a significant
      reduction of lens injury-induced regeneration. Growth arrest in optic nerves
      treated with BDNF and lens injury correlated with the formation of hypertrophic
      axonal swellings in the proximal optic nerve. These swellings were filled with
      numerous vesicular bodies, disorganized neurofilaments and degenerating
      organelles. Our results demonstrate that: (i) increased neuronal survival does
      not necessarily lead to enhanced axon regeneration and (ii) activation of
      survival and growth pathways may produce axonal dystrophy similar to that found
      in neurodegenerative disorders including glaucoma, Alzheimer's disease and
      multiple sclerosis. We propose that loss of axonal integrity may limit neuronal
      recovery in the injured, adult CNS.

PMID- 16418179
TI  - Mental chronometry of target detection: human thalamus leads cortex.
AB  - Attentive monitoring of environmental stimuli is most fundamental for rapid
      target detection. The aim of this study was to assess the timing of thalamic
      versus cortical processes involved in this cognitive operation. To this end,
      simultaneous depth and scalp EEG was recorded in eight patients with essential
      tremor, undergoing thalamic deep brain stimulation (DBS), when the DBS electrodes
      could be accessed via their temporarily externalized leads. The patients
      performed an oddball task consisting of 300 presentations of one frequent and two
      rare visual cues, appearing in randomized order. One of the rare cues was defined
      as a target, the occurrences of which had to be indicated by a button press
      (motor condition) or silently counted (non-motor condition). At the scalp and the
      thalamus, event-related potentials (ERP) were largest upon target presentation,
      with peak latencies in the time domain of classical P300 responses. Remarkably,
      target-specific thalamic ERP emerged significantly prior to scalp P300.
      Furthermore, whereas scalp ERP had a higher amplitude upon rare than upon
      frequent non-target signals, thalamic ERP were independent of stimulus
      probability. This pattern was identified during motor and non-motor task
      execution. We conclude that the human thalamus specifically supports the early
      recognition of target events and can widely distribute this label through its
      divergent cortical projections.

PMID- 16418180
TI  - Left-hemispheric dominance for articulation: a prospective study on acute
      ischaemic dysarthria at different localizations.
AB  - Dysarthria is a frequent symptom in cerebral ischaemia. However, speech
      characteristics of these patients have not previously been investigated in
      relation to lesion site in a prospective study. We investigated the auditory
      perceptual features in 62 consecutive patients with dysarthria due to a single,
      non-space-occupying cerebral infarction confirmed by MRI. Standardized speech
      samples of all patients were stored within 72 h after stroke onset using a
      digital tape recorder. Speech samples were assessed independently by two
      experienced speech therapists, who were unaware of the clinical and
      neuroradiological findings, using an interval scale ranging from 0 to 6.
      Separately assessed were features of articulation, phonation, prosody, and the
      global severity for a total of 31 items. Extracerebellar infarctions (85.5%) were
      located in the lower motor cortex (14.5%), striatocapsular region (46.8%) and
      base of the pons (24.2%). Isolated cerebellar infarctions were present in 14.5%
      of patients. There was a strong correlation between the findings of both
      examiners, showing identical scores, or only minor differences (<1 on the
      assessment scale) for 80% of all items. The average severity of dysarthria was
      2.9 +/- 1.3. Articulatory abnormalities were the predominant deviation
      characteristics, affecting in particular the production of consonants. However,
      phonatory and prosodic abnormalities were also frequently observed speech
      characteristics. As revealed by factor analysis of speech characteristics the
      total severity of dysarthria was mainly influenced by the impairment of
      articulation. Speech parameters describing characteristics of articulation and
      prosody showed significant side-to-side and area differences, while this effect
      was lacking for any voice parameter. Left cerebral lesions showed a more severe
      overall impairment of speech and articulation, independent of lesion topography.
      Thirty-eight of 62 patients were available for follow-up. Speech evaluation
      showed normal speech within weeks in 15 out of 38 patients (39.5%). In the other
      23 patients overall severity of dysarthria was mild. This is the first
      prospective study which describes speech characteristics of dysarthria due to
      acute unilateral cerebral infarctions. We could demonstrate that dysarthria in
      extracerebellar infarctions was more frequently caused by left-sided lesions and
      that the severity of dysarthria was more pronounced in left-sided lesions
      independent from lesion topography. All extracerebellar lesions were located
      along the course of the cortico-bulbar tract fibres. Compatible with a common
      pathophysiological basis of dysarthria in these patients, none of the 31 speech
      items differed significantly between subcortical and brainstem lesions.

PMID- 16418181
TI  - Association of the PIG3 promoter polymorphism with invasive bladder cancer in a
      Japanese population.
AB  - PIG3 (p53-induced gene 3) is one of the targets of TP53 and is involved in
      apoptosis. The promoter of PIG3 contains a variable number of tandem repeats
      (VNTRs) of pentanucleotides (TGYCC)n (Y = C or T) and the number of VNTRs was
      reported to be correlated with the activation by TP53. In this study, the
      clinical significance of the PIG3 promoter VNTRs was analyzed in the bladder
      cancer patients using the genome DNAs from 338 controls and 273 bladder cancer
      patients. There was no significant difference in the allele frequency of the PIG3
      promoter VNTRs between them. However, the presence of 14 or less repeats allele
      was associated with higher cancer grade (P = 0.038) and higher stage in relative
      risk (adjusted odds ratio = 2.31, 95% confidence interval = 1.05-5.90). These
      data suggested that the PIG3 promoter VNTRs was associated with generation of
      invasive bladder cancer.

PMID- 16418183
TI  - Is glossectomy necessary for late nodal metastases without clinical local
      recurrence after initial brachytherapy for N0 tongue cancer? A retrospective
      experience in 111 patients who received salvage therapy for cervical failure.
AB  - PURPOSE: To assess the efficacy of neck dissection (ND) without glossectomy (GL)
      for late nodal metastases without local recurrence after brachytherapy for N0
      tongue cancer. MATERIALS AND METHODS: Among 396 patients with N0 tongue cancer
      treated with brachytherapy, a retrospective analysis was performed in 111
      patients who were clinically diagnosed as having nodal metastases without local
      recurrence and whose neck lymph nodes turned out to be pathologically positive
      after salvage surgery. One hundred and five patients had undergone only ND (the
      ND group), six patients had undergone ND with GL (the ND+GL group). RESULTS: The
      5 year disease-free and cause-specific survival rates after salvage therapy for
      the 111 patients included in this study were 58.1 and 61.9%, respectively. In the
      ND group, there were only nine patients who had local recurrence after ND. In
      addition, only six patients (5.7%) had a local recurrence within 2 years in the
      ND group. Sixty-three patients were free of disease after ND, 31 patients had
      regional or distant metastases without local recurrence and two patients had
      progressive disease at ND. In the ND+GL group, four patients were alive without
      disease and two died from regional or distant metastases. None of the patients in
      the ND+GL group were found to have malignant tissue in the pathological findings
      from the excised tongue. CONCLUSION: GL should be avoided or suspended when the
      clinical evaluation had revealed cervical failure without apparent local
      recurrence in the mobile tongue cancer patients after initial brachytherapy.

PMID- 16418182
TI  - Biweekly paclitaxel and gemcitabine for patients with advanced urothelial cancer
      ineligible for cisplatin-based regimen.
AB  - BACKGROUND: To avoid cisplatin-related gastrointestinal, renal and other toxicity
      while maintaining efficacy in the palliative setting or second line
      chemotherapeutic regimen for cisplatin-resistant urothelial cancer,
      chemotherapeutic regimens have been investigated that do not include cisplatin.
      The current study was designed to evaluate efficacy, clinical feasibility and
      safety of gemcitabine and paclitaxel (GP) regimen in patients with metastatic
      urothelial cancer who were ineligible for standard cisplatin-based combination
      chemotherapy. METHODS: Gemcitabine 2500 mg/m(2) and paclitaxel 150 mg/m(2) were
      administered intravenously every 2 weeks for 23 patients (17 males and 6 females)
      with advanced urothelial cancer who were ineligible for cisplatin-based
      chemotherapy; metastatic disease being resistant to cisplatin-based chemotherapy
      regimen in 14, heavy toxicity in prior cisplatin-based chemotherapy in three,
      poor ECOG performance in two and impaired renal function in four. Average age was
      67 (53-77). Performance status was 0 in 18 patients, 1 in three patients and 2 in
      two patients. RESULTS: The overall response rate was 30% (95% CI 15.6-50.8%). Of
      the 23 patients, no patient attained CR and 7 patients had PR. In the cisplatin
      resistant group, the response rate was 14.2% (2/14; 95% CI 4.0-39.9%). In the
      remaining patients ineligible for cisplatin, the response rate was 55.5% (5/9;
      95% CI 26.6-81.1%). The median duration of response was 4 months (range 3-8). The
      median duration of survival for all patients was 12.1 months (95% CI 8.6-15.5).
      Myelosuppression, predominantly neutropenia, was the most common serious toxicity
      and toxicity of Grade 3 or greater was observed in six patients (26%). Among non
      hematological toxicity, neuralgia was the most commonly observed and occurred in
      nine patients (39%) although no patient had toxicity of Grade 3 or greater. Three
      patients had interstitial pneumonitis possibly attributed to gemcitabine. One
      patient developed severe bilateral disease after two cycles of the regimen, which
      was partially resolved with corticosteroid therapy. CONCLUSION: GP regimen is
      effective in some patients with cisplatin-resistant urothelial cancer and
      promising as second line chemotherapy. GP regimen is more effective and well
      tolerated as first line chemotherapy in patients ineligible for cisplatin-based
      chemotherapy. Toxicity is generally mild but care must be taken for patients with
      risk of interstitial pneumonitis. A further larger scale study is required to
      confirm the efficacy of the GP regimen.

PMID- 16418184
TI  - Phase I study of amrubicin hydrochloride and cisplatin in patients previously
      treated for advanced non-small cell lung cancer.
AB  - OBJECTIVE: A single-center phase I trial was designed to determine both the dose
      limiting toxicities and the maximum tolerated dose (MTD) for amrubicin
      hydrochloride in combination therapy with cisplatin for advanced non-small cell
      lung cancer (NSCLC) patients with prior chemotherapy. METHODS: Eligible patients
      received amrubicin and cisplatin on days 1 through 3 every 3 or 4 weeks.
      Cisplatin was administered at a fixed dosage of 20 mg/m(2) while the administered
      dose of amrubicin was started at 20 mg/m(2). Each group comprised 3 or 6
      patients. When dose limiting toxicities were noted in three or more of six
      patients at a particular level, that level was estimated to be the MTD. RESULTS:
      Fifteen patients were enrolled in this study, including 5 males and 10 females,
      with a median age of 57. The dose limiting toxicities included grade 4
      neutropenia which lasted 4 or more days and febrile neutropenia. The non
      hematologic toxicities were well managed and rarely severe. The MTD of amrubicin
      in this combination regimen was estimated to be 30 mg/m(2).A partial response was
      observed in 4 of 15 patients (27%). CONCLUSIONS: The recommended dose was thus
      determined to be 25 mg/m(2) amrubicin with 20 mg/m(2) cisplatin for 3 consecutive
      days. A phase II study is currently underway.

PMID- 16418185
TI  - Radical external beam radiotherapy for prostate cancer in Japan: results of the
      1999-2001 patterns of care process survey.
AB  - BACKGROUND: The Patterns of Care Study evaluated standards of practice for
      patients with clinically localized prostate cancer treated with radiotherapy in
      Japan. This study examined the influence of institutional stratification on care
      for patients receiving radical external beam radiotherapy. METHODS: A national
      survey of 66 institutions was conducted using two-stage cluster sampling, and
      detailed information was accumulated on 283 patients who received radiotherapy
      between 1999 and 2001. RESULTS: In A (academic) and B (non-academic)
      institutions, more than 80% of patients had intermediate or unfavorable risk
      disease. Although there were no significant differences in disease
      characteristics between A and B institutions, institutional stratification
      significantly affected radiotherapy practice patterns, such as the use of a CT
      based treatment planning (A1: 91.5%, B: 77.1%; P = 0.0007) and the use of
      conformal therapy (A: 56.4%, B: 24.1%; P < 0.0001). CT-based treatment planning
      and conformal therapy significantly influenced total radiation dose (P < 0.0001
      for each). Hormonal therapy was commonly used in both A and B institutions (A:
      89.0%, B: 90.7%). Many patients with a favorable prognosis (A: 62.5%, B: 91.7%)
      received hormonal therapy, and most patients with unfavorable risk disease (A:
      93.6%, B: 91.6%) also received hormonal therapy. CONCLUSION: During the period
      1999-2001, the majority of prostate cancer patients treated in Japan with radical
      external beam radiotherapy had advanced diseases. Institutional stratification
      significantly affected radiotherapy practice patterns, with the notable exception
      that radiotherapy was commonly combined with hormonal therapy regardless of the
      institutional stratification and individual risk.

PMID- 16418186
TI  - Parathyroid hormone-related protein-secreting uterine endometrioid
      adenocarcinoma.
AB  - The diagnosis of parathyroid hormone-related protein (PTHrP)-secreting metastatic
      uterine endometrioid cancer was made in a 32-year-old Japanese woman with humoral
      hypercalcemia of malignancy. The primary endometrial cancer had been removed, and
      the tumor was diagnosed as Grade 1 endometrioid adenocarcinoma with shallow
      myometrial invasion. Salvage chemotherapy (paclitaxel and calboplatin) was
      started from 5 months after surgery when recurrent tumors were detected in the
      peritoneum and liver. Despite the salvage chemotherapy, the tumor progressed and
      hypercalcemia became evident with elevated PTHrP whereas no bone metastasis was
      identified. To the best of our knowledge, this is the first reported case of
      hypercalcemia due to PTHrP secretion in uterine endometrioid adenocarcinoma.

PMID- 16418187
TI  - A phase II study of single-agent gemcitabine as a second-line treatment in
      advanced non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the single-agent gemcitabine in
      advanced non-small cell lung cancer (NSCLC) as second-line chemotherapy. METHODS:
      Between February 2002 and November 2004, a total of 27 patients, who had
      previously been treated with paclitaxel and platinum as first line chemotherapy,
      were enrolled in the study. Patients were treated with gemcitabine (1000 mg/m(2))
      on days 1, 8 and 15 in a 28 day cycle. The response was assessed every two
      cycles. Toxicities were evaluated according to common toxicity criteria (CTC).
      RESULTS: The median age was 62 (range, 46-79) years old. Among the 27 patients,
      26 were male. Twenty-three patients had an ECOG performance status of 0 or 1 and
      four patients had a status of 2. Pathologically, 24 patients had squamous cell
      carcinoma and 3 had adenocarcinoma. Partial responses were observed in 15
      patients. All patients were evaluated for response and toxicity. The overall
      response rate was 18.5% (95% confidence interval, 5-33%) and the median response
      duration was 17 (range, 7.4 to 49+) weeks. The median time to progression was 10
      (range, 7 to 34+) weeks. The median overall survival for all patients was 38
      (range, 10 to 122+) weeks. During a total of 87 cycles, granulocytopenia greater
      than CTC grade 2 occurred in 7%, thrombocytopenia in 1% and anemia in 24% of
      case. Non-hematologic toxicities were minor and easily controlled. CONCLUSION:
      This study confirms the activity and safety of the single-agent gemcitabine as a
      second-line therapy in pretreated patients with advanced NSCLC.

PMID- 16418188
TI  - Patterns of progression in gastrointestinal stromal tumor treated with imatinib
      mesylate.
AB  - BACKGROUND: Although most patients with gastrointestinal stromal tumor (GIST)
      treated with imatinib mesylate achieve remission or disease stabilization, a
      significant proportion show progressive disease (PD) with or without initial
      favorable responses. We evaluated and categorized the patterns of progression of
      metastatic or unresectable GIST treated with imatinib to identify the prognostic
      significance and contribution to further treatment decision-making. METHODS: We
      prospectively gathered clinical data from 62 GIST patients treated with imatinib
      mesylate (400 mg/day) over a median period of 26 months. Twenty-one of these
      patients showed evidence of PD based on Response Evaluation Criteria in Solid
      Tumor criteria. RESULTS: Four patterns of PD were defined: focal progression (FP,
      N = 4), general progression (GP, N = 6), new cystic lesion (NCL, N = 6) and new
      solid lesion (NSL, N = 5). The groups were found to differ in terms of time to
      progression and prior response to imatinib. The proportion of patients who
      responded to escalated doses of imatinib (600-800 mg/day) was significantly
      higher in NCL patients (P = 0.04). Overall survival and survival from the
      confirmation of PD were significantly better in NCL or FP patients compared with
      NSL or GP patients (P = 0.0157, P = 0.0013). CONCLUSIONS: We identified four
      patterns of disease progression based on radiographic criteria with different
      clinical characteristics and impact on survival. Knowledge of these patterns was
      relevant for early detection and may be helpful in further treatment decision
      making.

PMID- 16418189
TI  - Neonate-primed CD8+ memory cells rival adult-primed memory cells in antigen
      driven expansion and anti-viral protection.
AB  - Immunizations early in life, when the host is most susceptible to infection,
      allow protective immunological memory to develop. Decreasing the dose of Cas-Br-E
      murine leukemia virus when priming neonatal mice results in adult-like, Type 1
      protective responses, but the resulting memory cell populations are smaller than
      after adult priming. After secondary challenge, virus-specific CD8+ memory cell
      populations expand twice as much in neonate-primed mice as in adult-primed mice.
      We found that when equivalent numbers of virus-specific cells were transferred
      into virus-susceptible mice, protection from disease was similar whether donor,
      immune mice were primed as neonates or adults, and IL-4 did not alter in vivo
      virus-specific CD8+ memory cell effector function. Hence, neonate-primed CD8+
      cells develop into memory cells that rival adult-primed cells in proliferation
      and effector function.

PMID- 16418190
TI  - Are adults benefiting from state coverage expansions?
AB  - This study provides a rigorous evaluation of state efforts to expand insurance
      coverage in California, Massachusetts, New Jersey, and Wisconsin. Overall,
      parents in Wisconsin and parents and childless adults in Massachusetts
      experienced the largest expansions in public coverage, with few, if any,
      offsetting reductions in private coverage. In contrast, the coverage expansions
      for parents in California and New Jersey led to increased enrollment, but often
      at the expense of private coverage. Because constraints on state resources are
      putting pressure on expansion efforts, we find evidence that cutbacks will place
      more adults at risk of being uninsured.

PMID- 16418191
TI  - The RAGE G82S polymorphism is not associated with rheumatoid arthritis
      independently of HLA-DRB1*0401.

PMID- 16418192
TI  - Two types of autoantibody-mediated thrombocytopenia in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVES: To determine whether autoantibodies to two platelet-specific
      antigens, glycoprotein IIb/IIIa (GPIIb/IIIa) and thrombopoietin receptor (TPOR),
      contribute to thrombocytopenia in patients with systemic lupus erythematosus
      (SLE). METHODS: Circulating B cells producing anti-GPIIb/IIIa antibodies and
      serum anti-TPOR antibodies were measured in 32 SLE patients with
      thrombocytopenia, 30 SLE patients without thrombocytopenia, 92 patients with
      idiopathic thrombocytopenia and 60 healthy controls. The megakaryocyte density in
      bone-marrow smears from all the patients with thrombocytopenia was evaluated.
      RESULTS: Anti-GPIIb/IIIa and anti-TPOR antibody responses were more frequent in
      SLE patients with thrombocytopenia than in those without thrombocytopenia (88 vs
      17%, P<0.0001; and 22% vs 0%, P=0.01, respectively). The frequencies of these
      platelet-related antibodies were comparable between SLE patients with
      thrombocytopenia and patients with idiopathic thrombocytopenia. Twenty-nine (91%)
      SLE patients with thrombocytopenia had either anti-GPIIb/IIIa or anti-TPOR
      antibody, and six had both. In SLE patients with thrombocytopenia, the anti-TPOR
      positive patients had significantly higher frequencies of megakaryocytic
      hypoplasia and poorer therapeutic responses to corticosteroids and intravenous
      immunoglobulin than did the anti-TPOR-negative patients, most of whom had the
      anti-GPIIb/IIIa antibody alone. CONCLUSIONS: Anti-GPIIb/IIIa and anti-TPOR
      antibodies are major factors contributing to SLE-associated thrombocytopenia, but
      the clinical presentations associated with these autoantibodies are different.

PMID- 16418193
TI  - Serum alanine aminotransferase elevations correlate with serum creatine
      phosphokinase levels in myositis.

PMID- 16418194
TI  - Coeliac disease in patients with Kawasaki disease. Is there a link?
AB  - OBJECTIVE: Kawasaki disease (KD) is an acute febrile systemic vasculitis, mainly
      affecting infants and young children. Immunological abnormalities during the
      acute phase of KD have been described extensively. However, the occurrence of a
      second immunological disorder in a patient with a history of KD is rarely
      reported. We evaluated the presence of autoimmune thyroiditis and coeliac disease
      (CD) in patients with KD diagnosis. METHODS: Ninety consecutive children (57
      males and 33 females, median age 5.2 yr, age range 1.6-14.1 yr) with KD were
      evaluated. All patients were evaluated for thyroid function (thyroid-stimulating
      hormone, thyroxine and triiodothyronine), anti-thyroglobulin (TgA) and anti
      peroxidase (TPOA) antibodies, and antigliadin, anti-endomysium and
      antitransglutaminase antibodies. CD was confirmed by jejunal biopsy if the
      specific antibody profile was positive. One hundred and fifty Italian children,
      matched for age and sex and from the same geographic area, acted as controls.
      RESULTS: A total of five patients (three boys, two girls; 5.5%; P<0.05) were
      found positive for coeliac antibodies. In all of these patients the diagnosis of
      CD was confirmed histologically. Regarding thyroid function and autoantibodies,
      no patient showed subclinical hypothyroidism or autoimmune thyroiditis. No
      differences in the familial occurrence of autoimmune diseases between KD patients
      and controls were found (9.1 and 7.9%, respectively). CONCLUSIONS: Our data
      showed a higher prevalence of CD in children with KD, and this suggests that
      children with KD should be monitored carefully for CD. However, there was no
      increase in the prevalence of autoimmune thyroid diseases in patients with KD or
      the familial occurrence of autoimmune diseases.

PMID- 16418195
TI  - The association of PTPN22 with rheumatoid arthritis and juvenile idiopathic
      arthritis.

PMID- 16418196
TI  - Rituximab treatment for glomerulonephritis in HCV-associated mixed
      cryoglobulinaemia: efficacy and safety in the absence of steroids.
AB  - OBJECTIVE: Rituximab, an anti-CD20 monoclonal antibody, has been used in lupus
      nephritis and membranous idiopathic nephropathy and has proved effective in non
      renal manifestations of type II mixed cryoglobulinaemia (MC) syndrome. We
      investigated the possible efficacy and safety of rituximab in the treatment of
      cryoglobulinaemic nephritis. METHODS: Five patients with active, biopsy-proven,
      glomerulonephritis in hepatitis C virus (HCV)-related type II MC syndrome were
      treated with four weekly infusions of rituximab (375 mg/m2) in monotherapy,
      without steroids whenever possible. Rituximab was the first-line therapy in three
      cases. RESULTS: A rapid and sustained renal response was observed in all
      patients, in one of them without retreatment up to the last follow-up (month
      21+). Renal biopsy was repeated after 6 months in one patient and
      histopathological improvement was documented. Three patients relapsed, at months
      +5, +7 and +12 of follow-up, respectively. Two of them were then retreated with
      rituximab and again presented a rapid improvement in renal function. Maintenance
      therapy with rituximab was performed in two patients: nephritis remission was
      maintained in both. Fc-gamma receptor 3a (FcgammaRIIIa) genotype characterization
      was consistent with the clinical response observed. Rituximab also proved
      effective against other active MC manifestations, when present. No major side
      effects occurred and steroids were not required in the follow-up. CONCLUSIONS:
      Rituximab may provide effective and safe therapy in type II MC-related
      glomerulonephritis, possibly as first-line therapy, avoiding steroids and
      hazardous immunosuppressive treatment.

PMID- 16418197
TI  - Expression of ADAM9 (meltrin-gamma) around aseptically loosened total hip
      replacement implants.
AB  - OBJECTIVE: To investigate the involvement of a disintegrin and the
      metalloproteinase ADAM9 (meltrin-gamma) in the formation of multinuclear giant
      cells and osteoclasts in aseptic loosening of hip replacement implants. METHODS:
      We used in situ hybridization, immunohistochemical staining and western blotting
      of interface membrane surrounding loosened hip implants, macrophage-colony
      stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand
      (RANKL) costimulation and polymethyl methacrylate (PMMA) particle stimulation of
      human monocytes followed by immunofluorescence staining and flow cytometric
      analysis. RESULTS: Morphometric analysis revealed that the ADAM9+ area in the
      revision total hip replacement (THR) interface was larger than in primary THR
      samples (37.6+/-5.1 vs 5.2+/-0.8%, P=0.002). Double immunofluorescence staining
      showed that CD68+ interface tissue macrophages and multinuclear giant cells were
      ADAM9+. ADAM9 mRNA containing mononuclear and multinuclear cells was often seen
      in a close spatial relationship with other ADAM9+ cells. Western blotting
      disclosed a 50 kDa ADAM9 band in tissue extracts. Upon M-CSF and RANKL
      costimulation of human monocytes, the ADAM9 staining pattern changed over time
      and ADAM9+ cells formed bi- and multinuclear cells. Flow cytometry disclosed that
      cells of the monocyte/macrophage lineage changed from ADAM9-negative cells into
      strongly positive cells during a 3-day culture. CONCLUSION: ADAM9 is expressed in
      interface tissues around aseptically loosened THR implants. ADAM9 may play a role
      as a fusion molecule in the formation of multinuclear giant cells and osteoclasts
      from mononuclear precursors in diseases characterized by bone tissue destruction.

PMID- 16418199
TI  - Prevalence of radiographic osteoarthritis--it all depends on your point of view.
AB  - OBJECTIVES: Knee pain and disability in older people may occur in the apparent
      absence of radiographic osteoarthritis. However, the view chosen to define
      radiographic osteoarthritis may be critical. We have investigated the prevalence
      and compartmental distribution of radiographic osteoarthritis in people with knee
      pain using different combinations of three separate radiographic views. METHODS:
      We performed a population-based study of 819 adults aged 50 yr and over with knee
      pain (part of the Clinical Assessment Study - Knee [CAS(K)]). Three radiographic
      views were obtained: weight-bearing posteroanterior (PA)
      semiflexed/metatarsophalangeal view; supine skyline; and supine lateral. RESULTS:
      Complete data for all three views were available on 777 subjects. The
      distribution of compartmental radiographic osteoarthritis was 314 (40%) combined
      tibiofemoral/patellofemoral, 186 (24%) isolated patellofemoral, 31 (4%) isolated
      tibiofemoral and 246 (32%) normal. Hence, the overall prevalence of radiographic
      osteoarthritis was 531/777 (68.3%) in this symptomatic population. Using a PA
      view alone (reflecting tibiofemoral osteoarthritis only) would identify 56.7% of
      the 531, whilst the addition of a skyline or lateral view increased this to
      87.0%. When using both skyline and lateral views in addition to the PA view,
      98.7% cases of radiographic osteoarthritis were identified. In addition to
      prevalence, compartmental distribution altered markedly when different
      combinations of views were used. CONCLUSIONS: Multiple views detect more
      radiographic osteoarthritis than single views alone. When different combinations
      of views are used, the prevalence and compartmental distribution of
      osteoarthritis changes and this may alter the accepted relationship, or lack of
      it, between symptoms and radiographic change.

PMID- 16418198
TI  - Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from
      lipopolysaccharide-stimulated human monocytes/macrophages by different modes.
AB  - OBJECTIVES: TNF-alpha, IL-1 and IL-6 are known to have primary roles in the
      pathogenesis of rheumatoid arthritis and other inflammatory diseases. The anti
      rheumatic drug chloroquine has been shown to inhibit TNF-alpha, IL-1 and IL-6
      production from mononuclear phagocytes. We examined the underlying mechanisms
      involved in the chloroquine-induced inhibition of cytokine production. METHODS:
      Human peripheral blood mononuclear cells and monocytes/macrophages and monocytic
      U-937 and THP-1 cells were stimulated with lipopolysaccharide, and TNF-alpha, IL
      1beta and IL-6 production was measured by ELISA. Levels of mRNA were measured by
      northern blotting and reverse transcription-polymerase chain reaction. Synthesis
      of 26-kDa TNF-alpha precursor was measured by metabolic labelling and
      immunoprecipitation analysis. Transcription rate was determined by nuclear run-on
      assay. RESULTS: TNF-alpha release from the cells was inhibited by chloroquine,
      whereas the steady-state level of TNF-alpha mRNA and synthesis of 26-kDa TNF
      alpha precursor were not changed by chloroquine. In contrast, chloroquine-induced
      inhibition of IL-1beta and IL-6 release was accompanied by a decrease in their
      steady-state mRNA levels. The transcription rates of the IL-1beta and IL-6 genes
      were not changed by chloroquine, whereas the stability of IL-1beta and IL-6 mRNA
      was decreased by chloroquine. Weak-base amines such as methylamine and ammonium
      chloride had no effect on the production of TNF-alpha, whereas they partially
      blocked the production of IL-1beta and IL-6. CONCLUSIONS: Our results indicate
      that chloroquine-mediated inhibition of TNF-alpha, IL-1beta and IL-6 synthesis
      occurs through different modes in lipopolysaccharide-stimulated human
      monocytes/macrophages: it blocks the conversion of cell-associated TNF-alpha
      precursor to mature soluble protein, whereas it reduces the levels of IL-1beta
      and IL-6 mRNA, at least in part, by decreasing their stability and by a pH
      dependent mechanism.

PMID- 16418200
TI  - The genetic basis of the joint hypermobility syndromes.

PMID- 16418201
TI  - Patient perceptions of physical therapy within a trial for back pain treatments
      (UK BEAM) [ISRCTN32683578].
AB  - OBJECTIVES: To explore the views of participants in a randomized controlled trial
      of physical treatments for low back pain about the treatment packages they
      received in the trial. METHODS: Within a randomized controlled trial that found
      small to moderate benefits from adding a manipulation package or an exercise
      programme to general practice care, we elicited participants' views on the
      treatment using an open question in participant questionnaires. These data were
      analysed using an adapted framework approach. RESULTS: We received a total of
      1259 comments from 1334 participants. Participants randomized to usual general
      practice care reported dissatisfaction with receiving only 'usual care', which
      consisted of providing analgesic medication without providing an explanation for
      their pain. Those randomized to a manipulation package felt the intervention was
      appropriate to their needs and commonly reported striking benefits. Participants
      assigned to the exercise programme developed a sense of self-reliance in managing
      back pain, although some failed to be sufficiently motivated to continue their
      exercise regimen outside the classes. CONCLUSIONS: This qualitative analysis has
      found much clearer differences between the groups than the main quantitative
      analysis. This suggests that some of the added value from being allocated to
      additional physical treatment for low back pain is not being captured by existing
      methods of measurement. Improved methods of assessment that consider a wider
      range of domains may be needed when interpreting the added value of such
      treatments to individual patients.

PMID- 16418202
TI  - Signatures of differentially regulated interferon gene expression and
      vasculotrophism in the peripheral blood cells of systemic sclerosis patients.
AB  - OBJECTIVE: To obtain a global view of the immunological alterations occurring in
      early systemic sclerosis (SSc) by transcriptional profiling of peripheral blood
      cells (PBCs). METHODS: Oligonucleotide microarrays were used to compare PBC gene
      expression profiles in 18 SSc cases (<2 yr duration) and 18 controls matched for
      race, gender and ethnicity. SSc cases had no prior or current exposure to
      cytotoxic drugs. PAXgene tubes were used to stabilize RNA during phlebotomy.
      Changes in gene expression were independently validated by real-time polymerase
      chain reaction. RESULTS: SSc PBCs demonstrated differential expression of 18
      interferon-inducible genes. Six of these genes were identical to the interferon
      signature genes in lupus peripheral blood mononuclear cells. Notably, SSc PBCs
      also had increased expression of allograft inflammatory factor (AIF1) and several
      selectins and integrins involved in cellular adhesion to the endothelium. Global
      analysis of 284 known biological pathways revealed that 13 were differentially
      regulated in SSc PBCs, including two pathways (IL2RB and GATA3) that lead to
      T(H)2 polarization. CONCLUSIONS: Transcriptional profiling reliably discriminates
      between PBCs from SSc and normal donors despite the fact that they represent a
      heterogeneous cell population. Multiple biological pathways were differentially
      regulated in SSc PBCs, but a common thread across these pathways was alterations
      in protein tyrosine kinase 2beta and mitogen-activated protein kinase signalling.
      Although the SSc PBC gene expression profile demonstrated some parallels with the
      lupus interferon gene signature, there was also increased expression of
      transcripts encoding proteins that target PBCs to the endothelium, which might be
      relevant to the vasculopathy of SSc.

PMID- 16418203
TI  - Rheumatoid factors: what's new?

PMID- 16418204
TI  - Pulmonary manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-positive
      vasculitis.

PMID- 16418205
TI  - Insulin-facilitated increase of muscle protein synthesis after resistance
      exercise involves a MAP kinase pathway.
AB  - Recent studies have implicated the mTOR-signaling pathway as a primary component
      for muscle growth in mammals. The purpose of this investigation was to examine
      signaling pathways for muscle protein synthesis after resistance exercise.
      Sprague-Dawley rats (male, 6 mo old) were assigned to either resistance exercise
      or control groups. Resistance exercise was accomplished in operantly conditioned
      animals using a specially designed flywheel apparatus. Rats performed two
      sessions of resistance exercise, separated by 48 h, each consisting of 2 sets of
      25 repetitions. Sixteen hours after the second session, animals were killed, and
      soleus muscles were examined for rates of protein synthesis with and without
      insulin and/or rapamycin (mTOR inhibitor) and/or PD-098059 (PD; MEK kinase
      inhibitor). Results of this study demonstrated that rates of synthesis were
      higher (P < 0.05) with insulin after exercise compared with without insulin, or
      to control muscles, regardless of insulin. Rapamycin lowered (P < 0.05) rates of
      synthesis in controls, with or without insulin, and after exercise without
      insulin. However, insulin was able to overcome the inhibition of rapamycin after
      exercise (P < 0.05). PD had no effect on protein synthesis in control rats, but
      the addition of PD to exercised muscle resulted in lower (P < 0.05) rates of
      synthesis, and this inhibition was not rescued by insulin. Western blot analyses
      demonstrated that the inhibitors used in the present study were selective and
      effective for preventing activation of specific signaling proteins. Together,
      these results suggest that the insulin-facilitated increase of muscle protein
      synthesis after resistance exercise requires multiple signaling pathways.

PMID- 16418206
TI  - Muscle cell depolarization induces a gain in surface GLUT4 via reduced
      endocytosis independently of AMPK.
AB  - Contracting skeletal muscle increases glucose uptake to sustain energy demand.
      This is achieved through a gain in GLUT4 at the membrane, but the traffic
      mechanisms and regulatory signals involved are unknown. Muscle contraction is
      elicited by membrane depolarization followed by a rise in cytosolic Ca2+ and
      actomyosin activation, drawing on ATP stores. It is unknown whether one or more
      of these events triggers the rise in surface GLUT4. Here, we investigate the
      effect of membrane depolarization on GLUT4 cycling using GLUT4myc-expressing L6
      myotubes devoid of sarcomeres and thus unable to contract. K+-induced membrane
      depolarization elevated surface GLUT4myc, and this effect was additive to that of
      insulin, was not prevented by inhibiting phosphatidylinositol 3-kinase (PI3K) or
      actin polymerization, and did not involve Akt activation. Instead, depolarization
      elevated cytosolic Ca2+, and the surface GLUT4myc elevation was prevented by
      dantrolene (an inhibitor of Ca2+ release from sarcoplasmic reticulum) and by
      extracellular Ca2+ chelation. Ca2+-calmodulin-dependent protein kinase-II
      (CaMKII) was not phosphorylated after 10 min of K+ depolarization, and the CaMK
      inhibitor KN62 did not prevent the gain in surface GLUT4myc. Interestingly,
      although 5'-AMP-activated protein kinase (AMPK) was phosphorylated upon
      depolarization, lowering AMPKalpha via siRNA did not alter the surface GLUT4myc
      gain. Conversely, the latter response was abolished by the PKC inhibitors
      bisindolylmaleimide I and calphostin C. Unlike insulin, K+ depolarization caused
      only a small increase in GLUT4myc exocytosis and a major reduction in its
      endocytosis. We propose that K+ depolarization reduces GLUT4 internalization
      through signals and mechanisms distinct from those engaged by insulin. Such a
      pathway(s) is largely independent of PI3K, Akt, AMPK, and CaMKII but may involve
      PKC.

PMID- 16418207
TI  - Relationship of fat mass and serum estradiol with lower extremity bone in persons
      with chronic spinal cord injury.
AB  - In the spinal cord injury (SCI) population, a relationship between adiposity and
      leg bone has not been reported, nor one between serum estradiol and leg bone
      mass. A cross-sectional, comparative study of 10 male pairs of monozygotic twins
      discordant for SCI was performed. Relationships were determined among bone
      mineral density (BMD), bone mineral content (BMC), lean mass, fat mass, and serum
      sex steroids. In the twins with SCI, significant relationships were evident
      between leg BMD or BMC with total body percent fat (r2= 0.49, P < 0.05; r2= 0.45,
      P = 0.05), leg fat mass (r2 = 0.76, P < 0.0005; r2= 0.69, P = 0.005), and serum
      estradiol (r2= 0.40, P = 0.05; r2= 0.37, P = 0.05). By stepwise regression
      analysis, in the twins with SCI, leg fat mass was found to be the single most
      significant predictor of leg BMD or BMC (F = 12.01, r2= 0.76, P = 0.008; F =
      50.87, r2= 0.86, P < 0.0001). In the able-bodied twins, leg lean mass correlated
      with leg BMD and BMC (r2= 0.58, P = 0.01; r2= 0.87, P = 0.0001). By use of within
      pair differences, significant correlations were found for leg lean mass loss with
      leg BMD loss (r2= 0.56, P = 0.01) or leg BMC loss (r2= 0.64, P = 0.0005). In
      conclusion, in twins with SCI, significant correlations were observed between fat
      mass and leg BMD or BMC as well as between serum estradiol values and leg BMD.
      The magnitude of the leg muscle mass loss was correlated with the magnitude of
      bone loss.

PMID- 16418209
TI  - Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome:
      in defense of the Rotterdam criteria.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a very common endocrinopathy with a
      heterogeneous presentation whose etiology is still uncertain. Not surprisingly,
      therefore, the definition of, and diagnostic criteria for, PCOS remain
      controversial. OBJECTIVE: The objective of the study was to review and justify
      the basis for the recently revised definition of PCOS arising from the joint
      European Society for Human Reproduction & Embryology/American Society for
      Reproductive Medicine (ESHRE/ASRM) Rotterdam workshop in 2003. INTERVENTION(S):
      The Rotterdam criteria take account of the broad spectrum of presenting features
      of PCOS, including women with hyperandrogenism but regular menses and, more
      controversially, those with menstrual disturbance without overt androgen excess.
      POSITIONS: The Rotterdam criteria for definition and diagnosis of PCOS, in the
      opinion of this author, represent a significant advance in recognizing the broad
      spectrum of presentation of the syndrome and acknowledge that the clinical and
      biochemical features may vary with time within individuals. The important
      refinements when compared to the 1990 NIH definition of PCOS are: 1) inclusion of
      polycystic ovarian morphology; and 2) inclusion of subjects with hirsutism and
      regular menses. CONCLUSIONS: These new diagnostic criteria for PCOS reflect the
      significant advances, particularly from studies of familial PCOS, in
      understanding of the etiology of the syndrome and the basis for its
      heterogeneity. Under the revised diagnostic criteria, the inclusion of women with
      hyperandrogenism and regular cycles has met with general agreement. The inclusion
      of women with oligomenorrhea and polycystic ovaries who do not have clear
      evidence of androgen excess is, in the opinion of this author, also justified but
      remains a contentious issue and one that requires further investigation.

PMID- 16418208
TI  - Prognostic significance of human pituitary tumor-transforming gene
      immunohistochemical expression in differentiated thyroid cancer.
AB  - CONTEXT: Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed
      in a variety of primary neoplasias, including differentiated thyroid cancer
      (DTC). OBJECTIVE: The objective of this study was to examine the
      immunohistochemical expression of hPTTG in DTC and its association with known
      prognostic factors. DESIGN: hPTTG expression was analyzed by immunostaining on
      paraffin-embedded tissues. Clinical data were used to determine any associations
      between the expression of hPTTG and prognostic variables of DTC. A median follow
      up of 43 months allowed us to analyze the persistence of disease and the response
      to radioiodine therapy. SETTING: The study was conducted at a tertiary university
      hospital. PATIENTS: Ninety-five patients undergoing surgical resection for DTC (n
      = 60) or benign nodular thyroid disease (n = 35) were studied. MAIN OUTCOME
      MEASURE: The main outcome measure was the association between hPTTG expression
      and prognostic factors in DTC. RESULTS: Among DTC cases, 21 (35%) had low and 39
      (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was
      largely unstained. Among benign nodular thyroid disease cases, immunostaining was
      detected focally in eight (22.8%). A significant association was found between
      hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P <
      0.05). A significant association with TNM was also found, because 83.3% of
      advanced TNM stages showed elevated hPTTG (P < 0.05). The association between
      hPTTG overexpression and decreased radioiodine uptake during follow-up was also
      significant (P < 0.05). The expression levels of hPTTG were confirmed as an
      independent prognostic factor for persistent disease (relative risk, 3.0; 95%
      confidence interval, 1.1-8.7; P < 0.05). CONCLUSIONS: Immunohistochemical
      analysis of hPTTG is of potential value in the determination of tumor
      aggressiveness in DTC.

PMID- 16418210
TI  - Kallmann syndrome: somatic and germline mutations of the fibroblast growth factor
      receptor 1 gene in a mother and the son.
AB  - CONTEXT: Although Kallmann syndrome (KS) caused by heterozygous loss of function
      mutations of the fibroblast growth factor receptor 1 gene (FGFR1) is occasionally
      associated with characteristic features, such as dental agenesis and cleft
      palate, FGFR1 mutations remain unidentified in several KS patients with such
      characteristic features. SUBJECTS AND METHODS: We examined a 14-yr-old Japanese
      boy with hypogonadotropic hypogonadism, olfactory dysfunction, and dental
      agenesis and his fertile mother with olfactory dysfunction and dental agenesis.
      Direct sequencing was performed for FGFR1 using leukocyte genomic DNA from the
      proband and leukocyte and nail genomic DNA from the mother. To examine a possible
      somatic mutation, a specific forward primer was designed to introduce a BstXI
      site into the normal allele only, and nested PCR amplification, followed by BstXI
      digestion, was carried out three times with different reverse primers. RESULTS:
      After standard PCR amplifications, a heterozygous 2-bp deletion at exon 10
      (1317_1318delTG), which is predicted to cause a frameshift at the 439th codon for
      serine and resultant termination at the 461st codon (S439fsX461), was identified
      in the proband, but was not found in the mother. After selective amplification of
      the mutant allele, this deletion was detected in nail DNA, but not in leukocyte
      DNA, from the mother. CONCLUSION: The results suggest that the 2-bp deletion took
      place as a somatic mutation in the mother and was transmitted to the boy because
      of germline mosaicism. Such a somatic mutation occurs in some apparently FGFR1
      mutation-negative KS patients with dental agenesis.

PMID- 16418211
TI  - Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome:
      the Rotterdam criteria are premature.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is defined most commonly according to
      the proceedings of an expert conference sponsored by the National Institutes of
      Health (NIH) in April 1990, which noted the disorder as having 1)
      hyperandrogenism and/or hyperandrogenemia, 2) oligoovulation, and 3) exclusion of
      known disorders. Alternatively, another expert conference held in Rotterdam in
      May 2003 defined PCOS, after the exclusion of related disorders, by two of the
      following three features: 1) oligo- or anovulation, 2) clinical and/or
      biochemical signs of hyperandrogenism, or 3) polycystic ovaries. In essence, the
      Rotterdam 2003 expanded the NIH 1990 definition creating two new phenotypes: 1)
      ovulatory women with polycystic ovaries and hyperandrogenism, and 2)
      oligoanovulatory women with polycystic ovaries, but without hyperandrogenism.
      OBJECTIVE: The objective of this study was to ascertain the validity of using the
      Rotterdam 2003 criteria rather than the NIH 1991 criteria for the diagnosis of
      PCOS. INTERVENTION(S): Interventions included the use of the Rotterdam 2003
      criteria for diagnosing PCOS and, in particular, the proposal to define two new
      phenotypes as PCOS. POSITIONS: Available data suggest that hyperandrogenic
      ovulatory women with polycystic ovaries tend to have mild insulin resistance and
      mild evidence of ovarian dysfunction, although significantly less than women with
      anovulatory PCOS. However, whether these women will have an increased risk of
      infertility or metabolic complications, such as type 2 diabetes, remains to be
      determined. Alternatively, the risk of insulin resistance and long-term metabolic
      risks of oligoovulatory women with polycystic ovaries is even less well
      characterized and may be nonexistent. CONCLUSIONS: Because of the paucity of data
      on the two new phenotypes and their long-term implications and the potential
      negative impact on research, clinical practice, and patient insurability, the
      adoption of the Rotterdam 2003 criteria for defining PCOS should be considered
      premature. However, because polycystic ovaries are a frequent feature of PCOS, a
      modification of the NIH 1990 criteria is proposed. Additional research
      characterizing the phenotypes and associated morbidities of PCOS is urgently
      required.

PMID- 16418212
TI  - Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in
      vitro and therapeutic regression of experimental endometriosis in vivo by a novel
      nonsteroidal progesterone receptor agonist, tanaproget.
AB  - CONTEXT: Endometriosis, the growth of endometrial tissue outside the uterus, is
      principally an estrogen-dependent disease. In contrast, exposure to progesterone
      during pregnancy or therapeutically has been shown to provide benefit to some
      women with this disease. However, recent research suggests that the presence of
      endometriosis impairs the capacity of the eutopic endometrium to respond to
      endogenous progesterone. OBJECTIVE: Reduced progesterone responsiveness results
      in an elevated endometrial expression of matrix metalloproteinases (MMPs) during
      the secretory phase of the menstrual cycle in women with endometriosis. Although
      cyclic MMP expression is critical for endometrial growth and remodeling, the
      failure of progesterone to down-regulate MMPs may impair nidation and promote the
      invasive establishment of endometriosis. In the current study we examined the
      ability of a newly developed progesterone receptor (PR) agonist, tanaproget
      (TNPR), to down-regulate endometrial MMP expression in vitro and regress
      experimental endometriosis in vivo. SETTING: This study was performed at a
      university-based medical center. PARTICIPANTS: Asymptomatic volunteers and
      patients with endometriosis were studied. MAIN OUTCOME MEASURES: We examined the
      ability of TNPR to down-regulate endometrial MMP expression in vitro compared
      with that of natural progesterone and two currently marketed synthetic steroidal
      progestins. Using a human/mouse model of endometriosis, we also tested the in
      vivo ability of TNPR to regress ectopic lesions established by tissues with
      reduced progesterone sensitivity. RESULTS: TNPR effectively down-regulated MMP
      expression in vitro and induced significant reduction of lesions in mice with
      disease established by tissues from endometriosis patients. CONCLUSION: Given the
      positive preclinical pharmacological profile of TNPR that has recently been
      reported, additional development of this compound for the treatment of
      endometriosis is warranted.

PMID- 16418213
TI  - Extending the clinical heterogeneity of iodide transport defect (ITD): a novel
      mutation R124H of the sodium/iodide symporter gene and review of genotype
      phenotype correlations in ITD.
AB  - CONTEXT: Iodide transport defect (ITD) is an autosomal recessive disorder
      resulting in varying degrees of congenital hypothyroidism (CH) with goiter and
      low or absent radioiodide uptake (RIUT), as determined by thyroid scintigraphy,
      and low iodide saliva to plasma ratio. Defects of the sodium/iodide symporter
      gene (NIS) have been shown to cause ITD. OBJECTIVE: We describe molecular studies
      of NIS in a patient with ITD and genotype-phenotype correlation analysis in 31
      patients with NIS defects reported worldwide. DESIGN: NIS sequencing and
      functional studies of the new NIS mutation in vitro were performed. RESULTS: In a
      newborn with symptomatic CH and a large goiter, thyroid scintigraphy showed no
      RIUT (0%). NIS sequencing identified the new homozygous mutation, R124H, in exon
      2. This mutation was associated with abolition of iodide uptake in vitro when
      transfected in COS-7 cells. Immunocytochemical studies documented correct
      targeting of the mutated protein to the plasma membrane of transfected cells.
      Genotype-phenotype correlation analysis showed that the onset of hypothyroidism
      occurred during the neonatal period with four NIS mutations (neonatal onset of
      hypothyroidism genotype), during infancy with three NIS mutations (infancy onset
      of hypothyroidism genotype), and during childhood with three NIS mutations
      (childhood onset of hypothyroidism genotype). RIUT is a direct measure of
      residual NIS activity in vivo. Mean RIUT was lower in patients with the neonatal
      onset of hypothyroidism genotype (0.88 +/- 0.2%) than in the infancy onset of
      hypothyroidism (1.9 +/- 0.4%; P < 0.05) and childhood onset of hypothyroidism
      (2.6 +/- 0.7%; P < 0.05) genotypes. CONCLUSIONS: We identified a new NIS
      mutation, R124H, in a newborn with the complete clinical ITD phenotype. Genotype
      phenotype correlations suggest that age at hypothyroidism onset may be genotype
      specific and may depend on genotype-specific residual NIS activity.

PMID- 16418214
TI  - Missense mutation in the transcription factor NKX2-5: a novel molecular event in
      the pathogenesis of thyroid dysgenesis.
AB  - CONTEXT: Congenital hypothyroidism (CH) is a common endocrine disorder with an
      incidence of 1:3000-4000 at birth. In 80-85% of cases, CH is caused by defects in
      thyroid organogenesis, resulting in absent, ectopically located, and/or severely
      reduced gland [thyroid dysgenesis (TD)]. Mutations in genes controlling thyroid
      development have demonstrated that in a few cases, TD is a Mendelian trait.
      However, accumulating evidence supports the view that the genetics of TD are
      complex, possibly with a polygenic/multifactorial basis. A higher prevalence of
      congenital heart disease has been documented in children with CH than in the
      general population. Such an association suggests a possible pathogenic role of
      genes involved in both heart and thyroid development. NKX2-5 encodes a
      homeodomain-containing transcription factor with a major role in heart
      development, and mutations affecting this gene have been reported in individuals
      with congenital heart disease. OBJECTIVE: In the present work we investigated the
      possible involvement of NKX2-5 mutations in TD. RESULTS: Our results indicate
      that Nkx2-5(-/-) embryos exhibit thyroid bud hypoplasia, providing evidence that
      NKX2-5 plays a role in thyroid organogenesis and that NKX2-5 mutations contribute
      to TD. NKX2-5 mutational screening in 241 patients with TD allowed the
      identification of three heterozygous missense changes (R25C, A119S, and R161P) in
      four patients with TD. Functional characterization of the three mutations
      demonstrated reduced DNA binding and/or transactivation properties, with a
      dominant-negative effect on wild-type NKX2-5. CONCLUSION: Our results suggest a
      previously unknown role of NKX2-5 in the pathogenesis of TD.

PMID- 16418215
TI  - Nitric oxide in papillary thyroid carcinoma: induction of vascular endothelial
      growth factor D and correlation with lymph node metastasis.
AB  - PURPOSE: Vascular endothelial growth factor-D (VEGF-D) plays an important role in
      lymph node metastasis via lymphangiogenesis in papillary thyroid carcinoma (PTC).
      Although PTC metastasizes to regional lymph nodes at a high frequency, the
      regulation of VEGF-D expression is largely unknown. EXPERIMENTAL DESIGN:
      Nitrite/nitrate levels and VEGF-D production were assessed in K1 papillary
      thyroid carcinoma cells after induction and/or inhibition of nitric oxide (NO)
      synthesis. Formation of nitrotyrosine, a biomarker for peroxynitrate formation
      from NO in vivo, was analyzed in primary human PTC. RESULTS: The production of
      nitrite/nitrate and VEGF-D in K1 cells was increased by treatment with the NO
      donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate
      (DETA NONOate). The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester
      inhibited the increase in nitrate/nitrite and eliminated the increase in VEGF-D.
      High-grade nitrotyrosine staining was observed in 51.8% (29 of 56) of PTCs.
      Nitrotyrosine levels were significantly correlated with VEGF-D immunoreactivity
      and lymph node metastasis. CONCLUSIONS: Our data showed a role for NO in
      stimulating VEGF-D expression in vitro. The formation of its biomarker,
      nitrotyrosine, was also correlated with VEGF-D expression in human PTC. NO may
      induce lymph node metastasis via VEGF-D stimulation in PTC.

PMID- 16418216
TI  - Combined analysis of six lipoprotein lipase genetic variants on triglycerides,
      high-density lipoprotein, and ischemic heart disease: cross-sectional,
      prospective, and case-control studies from the Copenhagen City Heart Study.
AB  - CONTEXT: Genetic variants in lipoprotein lipase may affect triglycerides, high
      density lipoprotein (HDL), and risk of ischemic heart disease (IHD). OBJECTIVE:
      The objective of this study was to investigate the influence of T(-93)G, G(-53)C,
      Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein lipase genotypes on
      triglycerides, HDL, and IHD. DESIGN: The cross-sectional study involved 9004
      adults. The prospective study consisted of 8817 adults developing 1001 IHD events
      over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts
      of 915 and 1062 IHD patients, respectively. SETTING: The study was performed in
      the Danish general population (the Copenhagen City Heart Study). PARTICIPANTS:
      IHD was angina pectoris or myocardial infarction. MAIN OUTCOME MEASURES:
      Triglycerides, HDL, and IHD were the main outcome measures. RESULTS: Cross
      sectionally, triglycerides varied by genotype with 1.27 mmol/liter in women and
      1.22 mmol/liter in men. HDL cholesterol varied by genotype with 0.49 mmol/liter
      in women and 0.60 mmol/liter in men. Prospectively, 9Asn (with -93G)
      heterozygotes and homozygotes combined vs. noncarriers had a hazard ratio for IHD
      of 1.6 [95% confidence interval (CI), 1.2-2.3]; 291Ser and 447Ter did not change
      IHD risk. In the case-control study, combining the cohorts of IHD patients, 9Asn
      (with -93G) heterozygotes and homozygotes combined vs. noncarriers had an odds
      ratio for IHD of 1.5 (CI, 1.2-2.1). 291Ser and 447Ter did not change IHD risk.
      Stratified for apolipoprotein E genotype, the odds ratios for IHD in 9Asn (with 
      93G) heterozygotes and homozygotes combined vs. noncarriers were 2.6 (CI, 1.2
      5.5) among epsilon32 individuals and 2.4 (CI, 1.4-4.1) among epsilon43
      individuals. CONCLUSIONS: Genetic variation in lipoprotein lipase is associated
      with differences in plasma triglycerides greater than 1 mmol/liter and
      differences in HDL cholesterol greater than 0.5 mmol/liter. A 1.6-fold risk of
      IHD in 9Asn (with -93G) heterozygotes and homozygotes combined is influenced by
      apolipoprotein E genotype.

PMID- 16418217
TI  - The major vault protein is responsive to and interferes with interferon-gamma
      mediated STAT1 signals.
AB  - The major vault protein (MVP) is the main component of vaults, large
      ribonucleoprotein particles implicated in the regulation of cellular signaling
      cascades and multidrug resistance. Here, we identify MVP as an interferon gamma
      (IFN-gamma)-inducible protein. Treatment with IFN-gamma resulted in a significant
      upregulation of MVP promoter activity as well as mRNA and protein levels.
      Activation of MVP expression by IFN-gamma involved transcriptional upregulation
      through the JAK/STAT pathway based on an interaction of STAT1 with an interferon
      gamma-activated site (GAS) within the proximal MVP promoter. Mutation of this
      site distinctly reduced basal as well as IFN-gamma-stimulated MVP transcription.
      IFN-gamma also significantly enhanced the translation rate of MVP. Ectopic MVP
      overexpression in the MVP-negative lung cancer cell model H65 led to a
      downregulation of three known IFN-gamma-regulated genes, namely ICAM-1, CD13 and
      CD36. Additionally, presence of MVP in H65 cells blocked both basal and IFN-gamma
      induced ICAM-1 expression whereas downmodulation of endogenous MVP levels by
      shRNA enhanced IFN-gamma-induced ICAM-1 expression in U373 glioblastoma cells.
      MVP-mediated IFN-gamma insensitivity was accompanied by significantly reduced
      STAT1 phosphorylation at Y701 and diminished translocation of STAT1 into the
      nucleus. Summarizing, we identify MVP as an IFN-gamma-responsive gene interfering
      with IFN-gamma-activated JAK/STAT signals. These data further substantiate that
      the vault particle functions as a general interaction platform for cellular
      signaling cascades.

PMID- 16418218
TI  - Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin
      is integrin alpha v beta 3 specific.
AB  - Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin
      superfamily, and is mainly expressed in the tight junctions of both epithelial
      and endothelial cells. We have recently shown that JAM-A is involved in basic
      fibroblast growth factor (bFGF)-induced angiogenesis. Here, we show that, when
      ectopically expressed in human umbilical vein endothelial cells (HUVECs), JAM-A
      induced enhanced cell migration on vitronectin, but had no effect on fibronectin.
      Use of antibodies that block integrin function indicated that the migration on
      vitronectin is specific to integrin alpha(v)beta(3) and not to integrin
      alpha(v)beta(5). JAM-A-induced migration was inhibited by anti-JAM-A antibody.
      Additionally, overexpression of a JAM-A cytoplasmic domain deletion mutant failed
      to induce HUVEC migration. Addition of phosphoinositide 3-kinase and protein
      kinase C inhibitors blocked JAM-A-induced migration, suggesting that these
      kinases act downstream of JAM-A. Immunoprecipitation analysis showed that JAM-A
      interacts with integrin alpha(v)beta(3), and this association was increased by
      engagement of the ligand-binding site of the integrin by Arg-Gly-Asp-Ser (RGDS)
      peptide. Furthermore, activation of both focal adhesion kinase (FAK) and mitogen
      activated protein kinase (MAPK) on vitronectin was enhanced by JAM-A
      overexpression but not by its cytoplasmic domain deletion mutant. Taken together,
      these results suggest that signaling through JAM-A is necessary for
      alpha(v)beta(3)-dependent HUVEC migration and implicate JAM-A in the regulation
      of vascular function.

PMID- 16418219
TI  - Oculodentodigital dysplasia connexin43 mutations result in non-functional
      connexin hemichannels and gap junctions in C6 glioma cells.
AB  - Oculodentodigital dysplasia (ODDD) is a rare developmental disorder characterized
      by craniofacial and limb abnormalities. Over 35 separate mutations in human
      connexin43 (Cx43) causing ODDD have been identified. Several mutations are also
      associated with central nervous system involvement, including white-matter
      changes detected by magnetic resonance imaging. As Cx43 is abundantly expressed
      in astrocytes, we hypothesized that the mutant Cx43 proteins that produce
      neurological dysfunction have abnormal functional characteristics in astrocytes.
      To understand how ODDD-associated mutations affect Cx43 signaling in cells of
      glial origin, we conducted studies in rat C6 glioma cells, a communication
      deficient glial cell line that expresses low levels of Cx43. We generated stable
      cell lines expressing enhanced yellow fluorescent protein (eYFP)-tagged human
      Cx43 constructs encoding wild-type and six eYFP-tagged mutant Cx43 mutants: Y17S,
      G21R, A40V, F52dup, L90V and I130T. Of these, Y17S, L90V and I130T are associated
      with neurological abnormalities. We found that all mutants could be detected on
      the cell surface. Y17S, G21R, A40V, L90V and I130T formed triton-resistant
      plaques representing gap junctions, although the relative ability to form plaques
      was decreased in these mutants compared with the wild type. F52dup formed
      dramatically reduced numbers of plaques. Propidium iodide uptake experiments
      demonstrated that all mutants were associated with reduced connexin hemichannel
      function compared with wild type. Scrape-loading experiments performed on the
      same stable cell lines showed reduced gap junctional dye transfer in all mutants
      compared with the wild type. These studies demonstrated that ODDD-associated Cx43
      mutations result in non-functional connexin hemichannels and gap junction
      functions in a glial cell line regardless of whether the particular mutant is
      associated with neurological dysfunction.

PMID- 16418220
TI  - Desmocollin 3 is required for pre-implantation development of the mouse embryo.
AB  - Desmocollin 3 (Dsc3) is a transmembrane glycoprotein that belongs to the cadherin
      family of cell adhesion receptors. Together with desmoglein(s), it forms the
      transmembrane core of desmosomes, a multiprotein complex involved in cell
      adhesion, organization of the cytoskeleton, cell sorting and cell signaling.
      Previous reports have suggested that Dsc3 synthesis is largely restricted to
      stratified epithelia, and that it plays a role in the proper differentiation of
      these tissues during mammalian embryonic development. To test these hypotheses,
      we generated Dsc3-null mice. Unexpectedly, homozygous mutants show a pre
      implantation lethal phenotype. In fact, most mutants die even before mature
      desmosomes are formed in the embryo, suggesting a new and unexpected role of Dsc3
      during early development.

PMID- 16418221
TI  - Direct binding of SWAP-70 to non-muscle actin is required for membrane ruffling.
AB  - Membrane ruffling induced by growth factor stimulation is caused by actin
      remodeling, which is mediated by various signaling molecules including Rac. We
      have shown that SWAP-70, which binds phosphatidylinositol trisphosphate, is one
      such molecule required for membrane ruffling in mouse kidney cells. Here, we show
      that SWAP-70 directly binds to F-actin. The bacterially expressed C-terminal
      region of SWAP-70 co-sedimented with non-muscle F-actin, suggesting direct
      binding of SWAP-70 to F-actin. The binding was much weaker in muscle F-actin. A
      truncated mutant of SWAP-70 containing only the C-terminal region readily
      colocalizes with F-actin, supporting this idea. Full-length SWAP-70 does not
      colocalize with F-actin unless cells are stimulated with growth factors,
      suggesting the presence of a stimuli-dependent regulatory mechanism for actin
      binding activity in vivo. Overexpression of the mutant SWAP-70 lacking this
      binding domain inhibits the membrane ruffling induced by epidermal growth factor
      stimulation in COS7 cells. This dominant-negative effect is also observed in
      membrane ruffling induced by a dominant-active Rac, suggesting that SWAP-70
      cooperates with Rac. These results suggest that the binding activity of SWAP-70
      to non-muscle F-actin is required for membrane ruffling.

PMID- 16418222
TI  - Cytoskeletal dynamics and cell signaling during planar polarity establishment in
      the Drosophila embryonic denticle.
AB  - Many epithelial cells are polarized along the plane of the epithelium, a property
      termed planar cell polarity. The Drosophila wing and eye imaginal discs are the
      premier models of this process. Many proteins required for polarity establishment
      and its translation into cytoskeletal polarity were identified from studies of
      those tissues. More recently, several vertebrate tissues have been shown to
      exhibit planar cell polarity. Striking similarities and differences have been
      observed when different tissues exhibiting planar cell polarity are compared.
      Here we describe a new tissue exhibiting planar cell polarity - the denticles,
      hair-like projections of the Drosophila embryonic epidermis. We describe in real
      time the changes in the actin cytoskeleton that underlie denticle development,
      and compare this with the localization of microtubules, revealing new aspects of
      cytoskeletal dynamics that may have more general applicability. We present an
      initial characterization of the localization of several actin regulators during
      denticle development. We find that several core planar cell polarity proteins are
      asymmetrically localized during the process. Finally, we define roles for the
      canonical Wingless and Hedgehog pathways and for core planar cell polarity
      proteins in denticle polarity.

PMID- 16418223
TI  - Localised PtdIns(3,4,5)P3 or PtdIns(3,4)P2 at the phagocytic cup is required for
      both phagosome closure and Ca2+ signalling in HL60 neutrophils.
AB  - Several events accompany integrin-mediated phagocytosis by myeloid cells. These
      include local pseudopod and phagocytic cup formation followed by Ca(2+)
      signalling. However, there is also a role for localised phosphatidylinositol
      (3,4,5) trisphosphate [PtdIns(3,4,5)P(3)] production. Here we report that in
      neutrophilic HL-60 cells expressing PH-Akt-GFP, binding of iC3b-coated zymosan
      particles (2 microm in diameter) via beta2 integrin induces an incomplete
      phagocytic cup to form before either PtdIns(3,4,5)P(3) or phosphatidylinositol
      (3,4) bisphosphate [PtdIns(3,4)P(2)] production or Ca(2+) signalling. These
      phosphoinositides then accumulated locally at the site of the phagocytic cup and
      Ca(2+) signalling and phagosome closure follows immediately. Although
      photobleaching showed that PH-Akt-GFP was freely diffusible in the cytosol and
      able to dissociate from the phagocytic cup, it was restricted to the plasma
      membrane of the formed but open phagosome and failed to diffuse into the
      surrounding plasma membrane or neighbouring phagocytic cups even if connected.
      Inhibition of phosphoinositide (PI) 3-kinase or depletion of membrane cholesterol
      inhibited both Ca(2+) signalling and phagosome closure, but had no effect on
      particle binding or phagocytic cup formation. We therefore conclude that
      PtdIns(3,4,5)P(3) or PtdIns(3,4)P(2) generation was not required for the events
      that initiate the formation of the phagocytic cup, but that anchoring of
      PtdIns(3,4,5)P(3) at the phagocytic cup is an essential step for phagosome
      closure and Ca(2+) signalling.

PMID- 16418224
TI  - ARAP3 is essential for formation of lamellipodia after growth factor stimulation.
AB  - Rho and Arf family small GTPases control dynamic actin rearrangements and
      vesicular trafficking events. ARAP3 is a dual GAP for RhoA and Arf6 that is
      regulated by phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)], a
      product of the phosphoinositide 3-kinase (PI3K) signalling pathway. To
      investigate the physiological function of ARAP3, we used an RNAi-based approach
      in an endothelial cell model. ARAP3-deficient cells showed increased activities
      of RhoA and Arf6. Phenotypically, they were more rounded than control
      counterparts and displayed very fine stress fibres. ARAP3-deficient cells were
      not capable of producing lamellipodia upon growth factor stimulation, a process
      known to depend on PI3K and Rac activities. Rac was transiently activated in
      stimulated ARAP3 RNAi cells although its cellular localisation was altered, a
      likely consequence of increased Arf6 activity. We conclude that ARAP3 recruitment
      to sites of elevated PtdIns(3,4,5)P(3) is crucial to allow localised inactivation
      of RhoA and cycling of Arf6, both of which are necessary to allow growth factor
      stimulated formation of lamellipodia.

PMID- 16418225
TI  - MKLP1 requires specific domains for its dendritic targeting.
AB  - The mitotic kinesin-like protein 1 (MKLP1) is specifically localized to the
      dendrite of the developed neuron, but its targeting mechanism is still unclear.
      In this study, the role of distinct domains of MKLP1 in dendritic targeting was
      investigated by producing a series of enhanced green fluorescent protein (eGFP)
      tagged MKLP1 and its variant mutations, and studying the distribution of these
      molecules in cultured primary hippocampal neurons using fluorescence microscopy.
      We have found that: (a) full-length MKLP1(1-856)-eGFP was distributed to the
      dendrite of hippocampal neurons, not the axon; (b) deletion of the ;motor' domain
      prevented the dendritic distribution; (c) deletion of the ;tail' domain caused
      axonal appearance; (d) mutants devoid of the ;stalk' domain were still
      specifically distributed to the dendrite. The results indicate that the motor and
      tail regions of MKLP1 are important and significant for its localization to the
      dendrites. We also discuss the difference between the targeting of membrane
      anchoring proteins and the kinesin-like protein.

PMID- 16418226
TI  - The role of protein kinase C delta activation and STAT3 Ser727 phosphorylation in
      insulin-induced keratinocyte proliferation.
AB  - Activation of the STAT family of transcription factors is regulated by cytokines
      and growth factors. STAT tyrosine and serine phosphorylation are linked to the
      transcriptional activation and function of STAT. We have previously described a
      unique pathway inducing keratinocyte proliferation, which is mediated by insulin
      stimulation and depends on protein kinase C delta (PKCdelta). In this study, we
      assessed STAT3 activation downstream of this pathway and characterized the role
      of PKCdelta activation in STAT3 tyrosine and serine phosphorylation and
      keratinocyte proliferation. Following insulin stimulation, STAT3 interacted with
      PKCdelta but not with any other PKC isoform expressed in skin. Activated forms of
      PKCdelta and STAT3 were essential for insulin-induced PKCdelta-STAT3 activation
      in keratinocyte proliferation. Abrogation of PKCdelta activity inhibited insulin
      induced STAT3 phosphorylation, PKCdelta-STAT3 association and nuclear
      translocation. In addition, overexpression of STAT3 tyrosine mutant eliminated
      insulin-induced PKCdelta activation and keratinocyte proliferation. Finally,
      overexpression of a STAT3 serine mutant abrogated insulin-induced STAT3 serine
      phosphorylation and STAT3-induced keratinocyte proliferation, whereas STAT3
      tyrosine phosphorylation was induced and nuclear localization remained intact.
      This study indicates that PKCdelta activation is a primary regulator of STAT3
      serine phosphorylation and that PKCdelta is essential in directing insulin
      induced signaling in keratinocyte proliferation.

PMID- 16418227
TI  - CD9 controls the formation of clusters that contain tetraspanins and the integrin
      alpha 6 beta 1, which are involved in human and mouse gamete fusion.
AB  - The process of gamete fusion has been largely studied in the mouse and has
      revealed the crucial role of the tetraspanin CD9. By contrast, human gamete
      fusion remains largely unknown. We now show that an anti-alpha 6 integrin mAb
      (GoH3) strongly inhibited human sperm-egg fusion in human zona-free eggs.
      Furthermore, a mAb directed against CD151, a tetraspanin known to associate with
      alpha 6 beta1, partially inhibited sperm-egg fusion. By contrast, the addition of
      an anti-CD9 mAb to zona free eggs had no effect. The integrin alpha 6 beta1,
      CD151 and CD9 tetraspanins were evenly distributed on human zona-intact oocytes.
      On zona-free eggs, the integrin alpha 6 beta1 and tetraspanin CD151 patched and
      co-localized but the tetraspanin CD9 remained unchanged. CD9 mAb prevented alpha
      6 beta1 integrin clustering and gamete fusion when added prior to, but not after,
      zona removal. Antibody-mediated aggregation of integrin alpha 6 beta1 yielded
      patches that were bigger and more heterogeneous in mouse oocytes lacking CD9.
      Moreover, a strong labelling of alpha 6 beta1 could be observed at the sperm
      entry point. Altogether, these data show that CD9 controls the redistribution of
      some membrane proteins including the alpha 6 beta1 integrin into clusters that
      may be necessary for gamete fusion.

PMID- 16418228
TI  - Action spectrum for expression of the high intensity light-inducible Lhc-like
      gene Lhl4 in the green alga Chlamydomonas reinhardtii.
AB  - Lhl4 encodes a distant relative of light-harvesting Chl-a/b proteins in the green
      alga Chlamydomonas reinhardtii. Lhl4 mRNA markedly accumulated within 30 min
      after illumination and in proportion to the light intensity up to a fluence rate
      much higher than that required for photosynthesis. The high intensity light (HL)
      induced accumulation of Lhl4 mRNA required continuous illumination, and the mRNA
      level rapidly decreased when the cells were placed in the dark. HL only slightly
      stabilized the mRNA, suggesting that the HL-induced expression of the Lhl4 gene
      is primarily regulated at the level of transcription. Blue light was more
      effective for inducing Lhl4 gene expression than green or red light, and far-red
      light had no effect. The action spectrum for Lhl4 gene expression was examined at
      wavelengths between 325 and 775 nm using the Okazaki Large Spectrograph. The
      obtained spectrum showed a distinct peak in the blue region (450 nm) and a
      shoulder in the UV-A region (375 nm). The curve in the spectrum rose steeply in
      the short wavelength UV region. In addition, we observed two minor peaks in the
      green (575 nm) and the red (675 nm) regions. The action spectrum suggests that a
      blue/UV-A light photoreceptor with a flavin-based chromophore participates in the
      HL response of Lhl4 gene expression. However, the hypersensitivity to near UV-B
      light suggests the involvement of an unidentified UV light perception system in
      the expression of the Lhl4 gene.

PMID- 16418229
TI  - Adaptative response of Vitis root to anoxia.
AB  - The effect of anoxia on the energy economy of root cells was studied by measuring
      heat production, ethanol and ATP production, K(+) fluxes and electrical activity
      in two Vitis species, V. riparia and V. rupestris, that differ in their tolerance
      to anoxia. Anoxia triggered a marked decrease of metabolic activity (measured by
      microcalorimetry) and of ATP levels in both species. In V. riparia after the
      first 2 h of anoxia, the decrease in the rate of heat production was not
      associated with a further significant decrease in ATP content, whereas in V.
      rupestris the ATP level continued to decrease until very low values were reached.
      The concomitant increase in the rate of ethanol production did not compensate for
      the decreased aerobic ATP supply. In V. rupestris, anoxia typically led to energy
      deficit and ATP imbalance, together with the subsequent disruption of ion
      homeostasis and cell death. In V. riparia, the strong decrease in K(+) membrane
      permeability together with the fast down-regulation of the electrical signals
      allowed the cells to avoid severe ion imbalances during prolonged anoxic
      episodes.

PMID- 16418230
TI  - plprot: a comprehensive proteome database for different plastid types.
AB  - Different plant plastid types contain a distinct protein complement for
      specialized functions and metabolic activities. plprot was established as a
      plastid proteome database to provide information about the proteomes of
      chloroplasts, etioplasts and undifferentiated plastids. The current version of
      plprot features 2,043 protein entries and consists of two modules. Module one
      contains a BLAST search option and provides comparative information on the
      proteomes of different plastid types. The second module contains four searchable
      databases, three for each individual plastid type and one comprehensive composite
      database that provides the results of plastid proteome analyses from different
      laboratories. plprot is accessible at http://www.plprot.ethz.ch.

PMID- 16418232
TI  - Reversal by green light of blue light-stimulated stomatal opening in intact,
      attached leaves of Arabidopsis operates only in the potassium-dependent, morning
      phase of movement.
AB  - Green light reversal of blue light-stimulated stomatal opening was discovered in
      isolated stomata. The present study shows that the response also occurs in
      stomata from intact leaves. Arabidopsis thaliana plants were grown in a growth
      chamber under blue, red and green light. Removal of the green light opened the
      stomata and restoration of green light closed them to baseline values under
      experimental conditions that rule out a mesophyll-mediated effect. Assessment of
      the response to green light over a daily time course showed that the stomatal
      sensitivity to green light was observed only in the morning, which coincided with
      the use of potassium as a guard cell osmoticum. Sensitivity to green light was
      absent during the afternoon phase of stomatal movement, which was previously
      shown to be dominated by sucrose osmoregulation in Vicia faba. Hence, the shift
      away from potassium-based osmoregulation in guard cells is further postulated to
      entail a shift from blue light to photosynthesis as the primary component of the
      stomatal response to light. Stomata from intact leaves of the zeaxanthin-less,
      npq1 mutant of Arabidopsis failed to respond to the removal or restoration of
      green light in the growth chamber, or to short, high fluence pulses of blue or
      green light. These data confirm previous studies showing that npq1 stomata are
      devoid of a specific blue light response. In contrast, stomata from intact leaves
      of phot1 phot2 double mutant plants had a reduced but readily detectable response
      to the removal of green light and to blue and green pulses.

PMID- 16418231
TI  - Molecular characterization of true and ectopic gene targeting events at the
      acetolactate synthase gene in Arabidopsis.
AB  - Precise modification of plant genomes via gene targeting (GT) is important for
      the study of gene function in vivo. A reliable GT system using the
      protoporphyrinogen oxidase (PPO) gene in Arabidopsis was reported 4 years ago;
      however, there are no subsequent successful reports of GT in Arabidopsis. A
      previous study showed ectopic gene targeting (EGT) of the endogenous gene in two
      thirds of GT plants, which was an obstacle to efficient true gene targeting
      (TGT). The endogenous acetolactate synthase (ALS) gene is involved in the
      biosynthesis of branched chain amino acids in plants and is the site of action of
      several herbicides. To confirm the generality of the GT system in Arabidopsis,
      and to characterize the EGT event in plants in detail, we converted ALS from a
      herbicide (imazapyr)-susceptible to a -resistant form by GT. We obtained two
      imazapyr-resistant plants following GT. One of the targeting events was TGT while
      the other was EGT. After detailed Southern blotting, PCR and nucleotide sequence
      analysis of the EGT plant, we determined the genomic position and structure of
      the ectopically targeted site. Based on our findings, we discuss the possible
      mechanisms of EGT in plants.

PMID- 16418233
TI  - Control of the synthesis and subcellular targeting of the two GDH genes products
      in leaves and stems of Nicotiana plumbaginifolia and Arabidopsis thaliana.
AB  - Although the physiological role of the enzyme glutamate dehydrogenase which
      catalyses in vitro the reversible amination of 2-oxoglutarate to glutamate
      remains to be elucidated, it is now well established that in higher plants the
      enzyme preferentially occurs in the mitochondria of phloem companion cells. The
      Nicotiana plumbaginifolia and Arabidopis thaliana enzyme is encoded by two
      distinct genes encoding either an alpha- or a beta-subunit. Using antisense
      plants and mutants impaired in the expression of either of the two genes, we
      showed that in leaves and stems both the alpha- and beta-subunits are targeted to
      the mitochondria of the companion cells. In addition, we found in both species
      that there is a compensatory mechanism up-regulating the expression of the alpha
      subunit in the stems when the expression of the beta-subunit is impaired in the
      leaves, and of the beta-subunit in the leaves when the expression of the alpha
      subunit is impaired in the stems. When one of the two genes encoding glutamate
      dehydrogenase is ectopically expressed, the corresponding protein is targeted to
      the mitochondria of both leaf and stem parenchyma cells and its production is
      increased in the companion cells. These results are discussed in relation to the
      possible signalling and/or physiological function of the enzyme which appears to
      be coordinated in leaves and stems.

PMID- 16418234
TI  - Panta rhei (QAlign2): an open graphical environment for sequence analysis.
AB  - MOTIVATION: The first version of the graphical multiple sequence alignment
      environment QAlign was published in 2003. Heavy response from the molecular
      biological user community clearly demonstrated the need for such a platform.
      RESULTS: Panta rhei extends QAlign by several features. Major redesigns on the
      user interface, for instance, allow users to flexibily compose views for multiple
      projects. The new sequence viewer handles datasets with arbitrarily many and
      arbitrarily large sequences that may still be edited by guided block moving. More
      distance-based algorithms are available to interactively reconstruct phylogenetic
      trees which can now also be zoomed and navigated graphicaly. AVAILABILITY:
      Executables and the JAVA source code are available under the Apache license at
      http://gi.cebitec.uni-bielefeld.de/qalign CONTACT: qalign@cebitec.uni
      bielefeld.de.

PMID- 16418235
TI  - Inference of gene regulatory networks and compound mode of action from time
      course gene expression profiles.
AB  - MOTIVATION: Time series expression experiments are an increasingly popular method
      for studying a wide range of biological systems. Here we developed an algorithm
      that can infer the local network of gene-gene interactions surrounding a gene of
      interest. This is achieved by a perturbation of the gene of interest and
      subsequently measuring the gene expression profiles at multiple time points. We
      applied this algorithm to computer simulated data and to experimental data on a
      nine gene network in Escherichia coli. RESULTS: In this paper we show that it is
      possible to recover the gene regulatory network from a time series data of gene
      expression following a perturbation to the cell. We show this both on simulated
      data and on a nine gene subnetwork part of the DNA-damage response pathway (SOS
      pathway) in the bacteria E. coli. CONTACT: dibernardo@tigem.it SUPLEMENTARY
      INFORMATION: Supplementary data are available at http://dibernado.tigem.it

PMID- 16418236
TI  - An interactive power analysis tool for microarray hypothesis testing and
      generation.
AB  - MOTIVATION: Human clinical projects typically require a priori statistical power
      analyses. Towards this end, we sought to build a flexible and interactive power
      analysis tool for microarray studies integrated into our public domain HCE 3.5
      software package. We then sought to determine if probe set algorithms or organism
      type strongly influenced power analysis results. RESULTS: The HCE 3.5 power
      analysis tool was designed to import any pre-existing Affymetrix microarray
      project, and interactively test the effects of user-defined definitions of alpha
      (significance), beta (1-power), sample size and effect size. The tool generates a
      filter for all probe sets or more focused ontology-based subsets, with or without
      noise filters that can be used to limit analyses of a future project to
      appropriately powered probe sets. We studied projects from three organisms
      (Arabidopsis, rat, human), and three probe set algorithms (MAS5.0, RMA, dChip
      PM/MM). We found large differences in power results based on probe set algorithm
      selection and noise filters. RMA provided high sensitivity for low numbers of
      arrays, but this came at a cost of high false positive results (24% false
      positive in the human project studied). Our data suggest that a priori power
      calculations are important for both experimental design in hypothesis testing and
      hypothesis generation, as well as for the selection of optimized data analysis
      parameters. AVAILABILITY: The Hierarchical Clustering Explorer 3.5 with the
      interactive power analysis functions is available at www.cs.umd.edu/hcil/hce or
      www.cnmcresearch.org/bioinformatics. CONTACT: jseo@cnmcresearch.org

PMID- 16418237
TI  - Combining signals from spotted cDNA microarrays obtained at different scanning
      intensities.
AB  - MOTIVATION: The analysis of spotted cDNA microarrays involves scanning of color
      signals from fluorescent dyes. A common problem is that a given scanning
      intensity is not usually optimal for all spotted cDNAs. Specifically, some spots
      may be at the saturation limit, resulting in poor separation of signals from
      different tissues or conditions. The problem may be addressed by multiple scans
      with varying scanning intensities. Multiple scanning intensities raise the
      question of how to combine different signals from the same spot, particularly
      when measurement error is not negligible. RESULTS: This paper suggests a non
      linear latent regression model for this purpose. It corrects for biases caused by
      the saturation limit and efficiently combines data from multiple scans. Combining
      multiple scans also allows reduction of technical error particularly for cDNA
      spots with low signal. The procedure is exemplified using cDNA expression data
      from maize. AVAILABILITY: All methods were implemented using standard procedures
      available in the SAS/STAT module of the SAS System. Programming statements are
      available from the first author upon request. CONTACT: piepho@uni-hohenheim.de
      SUPPLEMENTARY INFORMATION: The supplementary data are available at Bioinformatics
      online.

PMID- 16418238
TI  - TAMAL: an integrated approach to choosing SNPs for genetic studies of human
      complex traits.
AB  - Investigators conducting studies of the molecular genetics of complex traits in
      humans often need rationally to select a set of single nucleotide polymorphisms
      (SNPs) from the hundreds or thousands available for a candidate gene.
      Accomplishing this requires integration of genomic data from distributed
      databases and is both time-consuming and error-prone. We developed the TAMAL
      (Technology And Money Are Limiting) web site to help identify promising SNPs for
      further investigation. For a given list of genes, TAMAL identifies SNPs that meet
      user-specified criteria (e.g. haplotype tagging SNPs or SNP predicted to lead to
      amino acid changes) from current versions of online resources (i.e. HapMap,
      Perlegen, Affymetrix, dbSNP and the UCSC genome browser). AVAILABILITY: TAMAL is
      a platform independent web-based application available free of charge at
      http://neoref.ils.unc.edu/tamal. SUPPLEMENTARY INFORMATION:
      http://neoref.ils.unc.edu/tamal/.

PMID- 16418239
TI  - Multi-detector row CT of hemoptysis.
AB  - Hemoptysis is symptomatic of a potentially life-threatening condition and
      warrants urgent and comprehensive evaluation of the lung parenchyma, airways, and
      thoracic vasculature. Multi-detector row computed tomographic (CT) angiography is
      a very useful noninvasive imaging modality for initial assessment of hemoptysis.
      The combined use of thin-section axial scans and more complex reformatted images
      allows clear depiction of the origins and trajectories of abnormally dilated
      systemic arteries that may be the source of hemorrhage and that may require
      embolization. Conditions such as bronchiectasis, chronic bronchitis, lung
      malignancy, tuberculosis, and chronic fungal infection are some of the most
      common underlying causes of hemoptysis and are easily detected with CT.
      "Cryptogenic" hemoptysis is common among smokers and warrants subsequent follow
      up imaging to exclude possible underlying malignancy. The bronchial arteries are
      the source of bleeding in most cases of hemoptysis. Contributions from the non
      bronchial systemic arterial system represent an important cause of recurrent
      hemoptysis following apparently successful bronchial artery embolization.
      Vascular anomalies such as pulmonary arteriovenous malformations and bronchial
      artery aneurysms are other important causes of hemoptysis. Multi-detector row CT
      angiography permits noninvasive, rapid, and accurate assessment of the cause and
      consequences of hemorrhage into the airways and helps guide subsequent
      management.

PMID- 16418240
TI  - Can CT pulmonary angiography allow assessment of severity and prognosis in
      patients presenting with pulmonary embolism? What the radiologist needs to know.
AB  - Computed tomographic (CT) pulmonary angiography has been established as a first
      line diagnostic technique in patients suspected of having pulmonary embolism.
      Risk stratification is important in patients with pulmonary embolism because
      optimal management, monitoring, and therapeutic strategies depend on the
      prognosis. Acute right-sided heart failure is known to be responsible for
      circulatory collapse and death in patients with severe pulmonary embolism. Acute
      right-sided heart failure can be assessed at CT pulmonary angiography by
      measuring the dimensions of right-sided heart cavities or upstream venous
      structures, such as the superior vena cava or azygos vein. The magnitude of
      pulmonary embolism can be calculated at CT pulmonary angiography by applying
      angiographic scores adapted for CT (Miller and Walsh scores) or dedicated CT
      scores (Qanadli and Mastora scores). The advent of CT pulmonary angiography
      performed with electrocardiographic gating permits new advances in assessment of
      acute right-sided heart failure, such as measurement of the ventricular ejection
      fraction. Although such findings may be useful for assessment of treatment
      effectiveness, their effect on prognosis in patients with severe pulmonary
      embolism is debated in the literature.

PMID- 16418242
TI  - Neuroendocrine tumors of the lung: clinical, pathologic, and imaging findings.
AB  - Neuroendocrine tumors of the lung arise from Kulchitzky cells of the bronchial
      mucosa and comprise typical carcinoid, atypical carcinoid, large cell
      neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC). At
      histopathologic analysis, these tumors demonstrate a progressive increase in the
      number of mitotic figures per 10 high-power fields of viable tumor and in the
      extent of necrosis, with typical carcinoid having the lowest values and SCLC
      having the highest. Typical carcinoid is less aggressive than atypical carcinoid,
      although these tumors have similar gross pathologic and radiologic features;
      LCNEC has a prognosis between that of atypical carcinoid and that of SCLC. SCLC
      is the most aggressive pulmonary neuroendocrine tumor and has the most specific
      imaging feature: mediastinal or hilar lymphadenopathy. At CT, carcinoid tumors
      appear as a spherical or ovoid nodule or mass with a well-defined and slightly
      lobulated border. When nonspherical, the tumor is elongated with its long axis
      parallel to adjacent bronchi. Calcification or ossification is seen in up to 30%
      of cases. The CT findings of LCNEC are nonspecific and are similar to those of
      other non-small cell lung cancers. Although there are some overlapping features
      between these tumors, integration of the clinical and imaging features may be
      helpful in differentiation of pulmonary neuroendocrine tumors.

PMID- 16418244
TI  - Pneumoconiosis: comparison of imaging and pathologic findings.
AB  - Pneumoconiosis may be classified as either fibrotic or nonfibrotic, according to
      the presence or absence of fibrosis. Silicosis, coal worker pneumoconiosis,
      asbestosis, berylliosis, and talcosis are examples of fibrotic pneumoconiosis.
      Siderosis, stannosis, and baritosis are nonfibrotic forms of pneumoconiosis that
      result from inhalation of iron oxide, tin oxide, and barium sulfate particles,
      respectively. In an individual who has a history of exposure to silica or coal
      dust, a finding of nodular or reticulonodular lesions at chest radiography or
      small nodules with a perilymphatic distribution at thin-section computed
      tomography (CT), with or without eggshell calcifications, is suggestive of
      silicosis or coal worker pneumoconiosis. Magnetic resonance imaging is helpful
      for distinguishing between progressive massive fibrosis and lung cancer. CT and
      histopathologic findings in asbestosis are similar to those in idiopathic
      pulmonary fibrosis, but the presence of asbestos bodies in histopathologic
      specimens is specific for the diagnosis of asbestosis. Giant cell interstitial
      pneumonia due to exposure to hard metals is classified as a fibrotic form of
      pneumoconiosis and appears on CT images as mixed ground-glass opacities and
      reticulation. Berylliosis simulates pulmonary sarcoidosis on CT images. CT
      findings in talcosis include small centrilobular and subpleural nodules or
      heterogeneous conglomerate masses that contain foci of high attenuation
      indicating talc deposition. Siderosis is nonfibrotic and is indicated by a CT
      finding of poorly defined centrilobular nodules or ground-glass opacities.

PMID- 16418245
TI  - Dual-energy subtraction chest radiography: what to look for beyond calcified
      nodules.
AB  - Dual-energy subtraction chest radiography is a robust and powerful tool that
      improves the ability to detect and accurately diagnose a wide variety of thoracic
      abnormalities on posteroanterior-lateral chest images. Dual-energy subtraction
      chest radiography has many advantages over conventional chest radiography that
      facilitate image interpretation. The major advantage of this imaging technique is
      that it more clearly depicts calcification, which greatly aids in characterizing
      pulmonary nodules. Dual-energy subtraction images are also helpful in the
      recognition of hilar and mediastinal masses; the detection of tracheal narrowing
      and vascular disease; the identification of bone, pleural, and chest wall
      abnormalities; and the localization of indwelling devices such as stents and
      catheters. However, dual-energy subtraction imaging also has some limitations of
      which the radiologist should be aware and requires a somewhat higher radiation
      dose than does conventional radiography.

PMID- 16418246
TI  - T1 signal hyperintensity in the sellar region: spectrum of findings.
AB  - T1 signal hyperintensity is a common finding at magnetic resonance imaging of the
      sellar region. However, this signal intensity pattern has different sources, and
      its significance depends on the clinical context. Normal variations in sellar T1
      signal hyperintensity are related to vasopressin storage in the neurohypophysis,
      the presence of bone marrow in normal and variant anatomic structures,
      hyperactive hormone secretion in the anterior pituitary lobe (eg, in newborns and
      pregnant or lactating women), and flow artifacts and magnetic susceptibility
      effects. Pathologic variations in T1 signal hyperintensity may be related to
      clotting of blood (in hemorrhagic pituitary adenoma, pituitary apoplexy, Sheehan
      syndrome, or thrombosed aneurysm) or the presence of a high concentration of
      protein (Rathke cleft cyst, craniopharyngioma, or mucocele), fat (lipoma, dermoid
      cyst, lipomatous meningioma), calcification (craniopharyngioma, chondroma,
      chordoma), or a paramagnetic substance (manganese, melanin). After treatment, T1
      signal hyperintensity may result from the presence of materials used for surgical
      packing (gelatin sponge, fat); from compression of the cavernous sinus and
      reduction of the venous flow, caused by overpacking of the operative bed; or from
      hormone hypersecretion by a remnant of normal tissue in the anterior lobe of the
      pituitary gland.

PMID- 16418247
TI  - Middle and inner ear: improved depiction with multiplanar reconstruction of
      volumetric CT data.
AB  - Many anatomic structures of the middle and inner ear are not optimally depicted
      at computed tomography (CT) with image reconstruction in the standard axial and
      coronal planes. Recent advances in multidetector CT, including the development of
      scanners with 32 detector rows, allow the acquisition of isotropic voxels that
      can be reconstructed in any plane of section. This technique gives radiologists
      the opportunity to visualize the anatomic structures of the middle and inner ear
      (the ossicular chain, stapedial footplate-oval window complex, round window,
      cochlea, vestibular aqueduct, and bones of the superior semicircular canal and
      facial nerve canal) in greater detail and may help increase the accuracy of CT
      for the diagnosis of diseases of the middle and inner ear.

PMID- 16418248
TI  - Eponyms in radiology of the digestive tract: historical perspectives and imaging
      appearances. Part I. Pharynx, esophagus, stomach, and intestine.
AB  - Eponyms serve as a means of honoring individuals who have made important
      discoveries and observations. Eponyms are frequently encountered in the field of
      radiology, particularly in radiology of the digestive tract. However, the use of
      eponyms may fail to convey a precise meaning or definition and could lead to
      miscommunication. Moreover, in some instances, more than one individual may have
      contributed to the discovery or description of a particular anatomic structure or
      disease, whereas in others, an eponym may have been incorrectly applied initially
      and propagated for years in the medical literature. Nevertheless, radiologic
      eponyms are a means of honoring those who have made lasting contributions to the
      field of radiology, and familiarity with these eponyms is important for proper
      reporting and accurate communication. In addition, the acquisition of some
      historical knowledge about those whose names are associated with various
      structures or pathologic conditions brings some humanity back into the science of
      medicine.

PMID- 16418249
TI  - CT and PET in stomach cancer: preoperative staging and monitoring of response to
      therapy.
AB  - Stomach cancer is one of the leading causes of cancer mortality worldwide.
      Complete resection of a gastric tumor and adjacent lymph nodes represents the
      only potentially curative intervention. Computed tomography (CT) has remained the
      modality of choice for the preoperative staging of gastric cancer and for follow
      up. A recently developed advanced CT technique that makes use of thin sections,
      optimal contrast material enhancement, and multiplanar reformation allows more
      accurate staging. However, CT may be limited in the identification of nonenlarged
      lymph node metastasis, peritoneal dissemination, and small hematogenous
      metastasis. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy
      d-glucose (FDG) has been recognized as a useful diagnostic technique in clinical
      oncology. FDG PET allows scanning of a larger volume than is possible with CT.
      Although FDG PET is not an appropriate first-line diagnostic procedure in the
      detection of stomach cancer and is not helpful in tumor staging, it may play a
      valuable role in the detection of distant metastases, such as those of the liver,
      lungs, adrenal glands, ovaries, and skeleton. FDG PET may also be helpful in the
      follow-up of patients undergoing chemotherapy, as it allows the identification of
      early response to treatment. Further studies are needed to determine the efficacy
      of FDG PET in the detection of local nodal metastases and peritoneal
      dissemination. Nevertheless, the combined use of CT and PET can be helpful in the
      preoperative staging of stomach cancer and in the therapeutic monitoring of
      affected patients.

PMID- 16418250
TI  - Causes of facial swelling in pediatric patients: correlation of clinical and
      radiologic findings.
AB  - Facial swelling is a common clinical problem in pediatric patients. The causes of
      swelling are diverse, and knowledge of the typical clinical and imaging
      manifestations and the most common sites of occurrence of these conditions is
      needed to formulate a differential diagnosis. The general clinical manifestations
      may be classified into the following four groups: (a) acute swelling with
      inflammation, (b) nonprogressive swelling, (c) slowly progressive swelling, and
      (d) rapidly progressive swelling. Conditions that may account for acute swelling
      accompanied by inflammation include lymphadenitis, sinusitis, odontogenic
      infection, and abscess. Contrast-enhanced computed tomography is the modality of
      choice for detection of abscesses requiring surgical drainage. Nonprogressive
      midfacial swelling is suggestive of a congenital anomaly (eg, a cephalocele,
      nasal glioma, or nasal dermoid or epidermoid cyst). Slowly progressive swelling
      may indicate the presence of a neurofibroma, hemangioma, lymphangioma, vascular
      malformation, or pseudocyst, or of fibrous dysplasia. The differential diagnosis
      for rapidly progressive facial swelling in association with cranial nerve
      deficits should include rhabdomyosarcoma, Langerhans cell histiocytosis, Ewing
      sarcoma, osteogenic sarcoma, and metastatic neuroblastoma.

PMID- 16418251
TI  - Differential diagnosis of intracranial cystic lesions at head US: correlation
      with CT and MR imaging.
AB  - The differential diagnosis of intracranial cystic lesions at head ultrasonography
      (US) includes a broad spectrum of conditions: (a) normal variants, (b)
      developmental cystic lesions, (c) cysts due to perinatal injury, (d) vascular
      cystlike structures, (e) hemorrhagic cysts, and (f) infectious cysts. These
      lesions vary in prevalence from common (cavum of the septum pellucidum,
      subependymal cyst, choroid plexus cyst) to rare (vein of Galen malformation). US
      can provide important information about the anatomic location, size, and shape of
      the lesions as well as their mass effect on adjacent structures. Differential
      diagnosis may be difficult because there is substantial overlap of US features
      between many of these conditions. However, if careful attention is paid to the
      location and characteristics of the cyst, a more specific diagnosis may be
      suggested. Understanding the spectrum of appearances of the various intracranial
      cystic lesions at head US improves the diagnostic yield, enables one to
      understand their pathogenesis, and facilitates patient care.

PMID- 16418252
TI  - Cardiac MR imaging assessment following tetralogy of fallot repair.
AB  - Survivors of tetralogy of Fallot (TOF) repair constitute a large and growing
      population of patients. Although postsurgical outcome is generally favorable, as
      these patients move into adulthood, late morbidity is becoming more prevalent and
      the notion that TOF has been "definitively repaired" is increasingly being
      challenged. Recent evidence suggests that adverse long-term postsurgical outcome
      is related to chronic pulmonary regurgitation, right ventricular dilatation, and
      deteriorating ventricular function. Cardiac magnetic resonance (MR) imaging has
      been established as an accurate technique for quantifying ventricular size,
      ejection fraction, and valvular regurgitation. Cardiac MR imaging does not expose
      the patient to ionizing radiation and is therefore ideal for serial postsurgical
      follow-up. Familiarity with the anatomic basis of TOF, the surgical approaches to
      repair, and postrepair sequelae is essential for performing and interpreting
      cardiac MR imaging examinations. For example, awareness of the complications and
      sequelae that can occur will assist in determining when to intervene to preserve
      ventricular function and will improve long-term outcome. Technical facility is
      necessary to tailor the examination to the individual patient (eg, familiarity
      with non-breath-hold modifications that allow evaluation of young and less
      compliant patients). The radiologist can play an essential role in the treatment
      of patients with repaired TOF by providing noninvasive anatomic and physiologic
      cardiac MR imaging data. Further technologic advances in cardiac MR imaging are
      likely to bring about new applications, better normative data, and more
      examinations that are operator independent.

PMID- 16418253
TI  - Cardiovascular complications of human immunodeficiency virus infection.
AB  - The heart and great vessels are not the sites most frequently affected by
      opportunistic infections and neoplastic processes in patients with acquired
      immune deficiency syndrome (AIDS). However, cardiovascular complications occur in
      a significant number of such patients and are the immediate cause of death in
      some. The spectrum of cardiovascular complications of AIDS that may be depicted
      at imaging includes dilated cardiomyopathy, pericardial effusion, human
      immunodeficiency virus-associated pulmonary hypertension, endocarditis,
      thrombosis, embolism, vasculitis, coronary artery disease, aneurysm, and cardiac
      involvement in AIDS-related tumors. To aid accurate diagnosis and appropriate
      treatment planning, radiologists should be familiar with the imaging appearance
      of each of these complications.

PMID- 16418254
TI  - Renal cell carcinoma: unusual imaging manifestations.
AB  - Unusual radiologic manifestations of a renal cell carcinoma (RCC) can present a
      diagnostic challenge. These manifestations include bilateral synchronous
      multifocal tumors, a small RCC with synchronous adrenal metastasis, and RCC
      associated with bulky abdominal lymphoma. Less common manifestations include
      multiseptated cystic carcinoma simulating a moderately complex renal cyst at
      ultrasonography (US), paraaortic metastatic adenopathy as the only sign of an
      undetectable primary renal neoplasm, RCC causing a large arteriovenous fistula,
      RCC simulating angiomyolipoma, and a nonfunctioning kidney due to
      transparenchymal renal propagation of cancer associated with a tumor thrombus
      occluding the renal vein. Radiologists should be aware of the possibility of
      tumor multifocality or of adrenal metastases from a high-grade small renal tumor,
      as well as of the association of RCC with lymphoma. They should also be aware of
      the importance of following up a multiseptated cystic mass found at US or a
      Bosniak category IIF renal cyst, since these lesions can serve as early
      indicators of cystic carcinoma. Because the clinical implications of and
      therapeutic strategies for RCC vary depending on imaging characterization of the
      nature and extent of the disease, familiarity with its more unusual radiologic
      manifestations facilitates accurate diagnosis and management.

PMID- 16418255
TI  - From the archives of the AFIP: benign fibrous tumors and tumorlike lesions of the
      mesentery: radiologic-pathologic correlation.
AB  - Mesenteric fibromatosis, sclerosing mesenteritis, inflammatory pseudotumor, and
      extrapleural solitary fibrous tumor constitute a loosely associated group of
      benign fibrous tumors and tumorlike lesions of the mesentery. These lesions are
      linked histologically by the presence of fibroblasts or fibrosis and anatomically
      by their location within the mesentery. Although rare, and distinctly different
      in pathogenesis and biologic behavior, these fibrous lesions have pathologic and
      radiologic features that overlap with one another and with more common neoplastic
      and nonneoplastic lesions of the mesentery. Mesenteric fibromatosis is a locally
      aggressive, benign proliferative process that may occur sporadically or in
      association with familial adenomatous polyposis. It most frequently manifests as
      a focal mesenteric mass and may simulate lymphoma, metastatic disease, or a soft
      tissue sarcoma. Sclerosing mesenteritis is a rare idiopathic disorder that most
      commonly produces a stellate mass within the mesentery and should be
      differentiated from metastatic disease, specifically metastatic carcinoid,
      because it frequently responds to conservative or medical management.
      Inflammatory pseudotumor (inflammatory myofibroblastic tumor) is a benign,
      chronic inflammatory disorder of unknown cause that manifests as a solid
      mesenteric mass, indistinguishable from malignancy. Extrapleural solitary fibrous
      tumor is a tumor of submesothelial origin that is identical to the solitary
      fibrous tumor of the pleura. When located in the mesentery or peritoneal cavity,
      extrapleural solitary fibrous tumor has an imaging pattern that must be
      differentiated from metastatic disease, soft-tissue sarcomas, and other benign
      and malignant neoplasms of the mesentery and peritoneum. Knowledge of this group
      of benign fibrous tumors and tumorlike lesions of the mesentery is important in
      the preoperative evaluation of a mesenteric mass.

PMID- 16418256
TI  - Best cases from the AFIP: epithelioid hemangioendothelioma of bone.

PMID- 16418257
TI  - Best cases from the AFIP: carcinoma of the esophagus: varicoid pattern.

PMID- 16418258
TI  - AAPM/RSNA physics tutorial for residents: MR artifacts, safety, and quality
      control.
AB  - Artifacts in magnetic resonance (MR) imaging result from the complex interaction
      of contemporary imager subsystems, including the main magnet, gradient coils,
      radiofrequency (RF) transmitter and receiver, and reconstruction algorithm used.
      An understanding of the sources of artifacts enables optimization of the MR
      imaging system performance. The increasing clinical use of very high magnetic
      field strengths, high-performance gradients, and multiple RF channels also
      mandates renewed attention to the biologic effects and physical safety of MR
      imaging. Radiologists should be aware of the potential physiologic effects of
      prolonged exposure to magnetic fields, acoustic noise, and RF energy during MR
      imaging and should use all the available methods for avoiding accidents and
      adverse effects. Imaging equipment should be regularly tested and monitored to
      ensure its stability and the uniformity of its functioning. Newly installed or
      upgraded MR systems should be tested by a physicist or qualified engineer before
      use. In addition, the authors recommend participation in the MR imaging
      accreditation program of the American College of Radiology to establish the
      initial framework for an adequate quality assurance program, which then can be
      further developed to fulfill local institutional needs.

PMID- 16418259
TI  - Informatics in radiology (infoRAD): navigating the fifth dimension: innovative
      interface for multidimensional multimodality image navigation.
AB  - The display and interpretation of images obtained by combining three-dimensional
      data acquired with two different modalities (eg, positron emission tomography and
      computed tomography) in the same subject require complex software tools that
      allow the user to adjust the image parameters. With the current fast imaging
      systems, it is possible to acquire dynamic images of the beating heart, which add
      a fourth dimension of visual information-the temporal dimension. Moreover, images
      acquired at different points during the transit of a contrast agent or during
      different functional phases add a fifth dimension-functional data. To facilitate
      real-time image navigation in the resultant large multidimensional image data
      sets, the authors developed a Digital Imaging and Communications in Medicine
      compliant software program. The open-source software, called OsiriX, allows the
      user to navigate through multidimensional image series while adjusting the
      blending of images from different modalities, image contrast and intensity, and
      the rate of cine display of dynamic images. The software is available for free
      download at http://homepage.mac.com/rossetantoine/osirix.

PMID- 16418262
TI  - Platelets and platelet adhesion support angiogenesis while preventing excessive
      hemorrhage.
AB  - Platelets contain both pro- and antiangiogenic factors, but their regulatory role
      in angiogenesis is poorly understood. Although previous studies showed that
      platelets stimulate angiogenesis in vitro, the role of platelets in angiogenesis
      in vivo is largely uncharacterized. To address this topic, we used two in vivo
      approaches, the cornea micropocket assay and the Matrigel model, in four animal
      models: thrombocytopenic, Lyst(bg) (platelet storage pool deficiency),
      glycoprotein (GP) Ibalpha/IL4R transgenic (lacking extracellular GPIbalpha, the
      receptor for von Willebrand factor as well as other adhesive and procoagulant
      proteins), and FcgammaR(-/-) (lacking functional GPVI, the collagen receptor)
      mice. Adult mice were rendered thrombocytopenic by i.p. administration of an
      antiplatelet antibody. The number of growing vessels in the thrombocytopenic mice
      was lower in the cornea assay, and they showed significantly increased appearance
      of hemorrhage compared with mice treated with control IgG. The thrombocytopenic
      mice also showed more protein leakage and developed hematomas in the Matrigel
      model. GPIbalpha/IL4R transgenic mice presented increased hemorrhage in both
      assays, but it was less severe than in the platelet-depleted mice. FcgammaR(-/-)
      and Lyst(bg) mice showed no defect in experimental angiogenesis. Intravital
      microscopy revealed a >3-fold increase in platelet adhesion to angiogenic vessels
      of Matrigel compared with mature quiescent skin vessels. Our results suggest that
      the presence of platelets not only stimulates angiogenic vessel growth but also
      plays a critical role in preventing hemorrhage from the angiogenic vessels. The
      adhesion function of platelets, as mediated by GPIbalpha, significantly
      contributes to the process.

PMID- 16418263
TI  - Somitic origin of limb muscle satellite and side population cells.
AB  - Repair of mature skeletal muscle is mediated by adult muscle progenitors.
      Satellite cells have long been recognized as playing a major role in muscle
      repair, whereas side population (SP) cells have more recently been identified as
      contributing to this process. The developmental source of these two progenitor
      populations has been considerably debated. We explicitly tested and quantified
      the contribution of embryonic somitic cells to these progenitor populations.
      Chick somitic cells were labeled by using replication-defective retroviruses or
      quail/chick chimeras, and mouse cells were labeled by crossing somite-specific,
      Pax3-derived Cre driver lines with a Cre-dependent reporter line. We show that
      the majority of, if not all, limb muscle satellite cells arise from cells
      expressing Pax3 specifically in the hypaxial somite and their migratory
      derivatives. We also find that a significant number of, but not all, limb muscle
      SP cells are derived from the hypaxial somite. Notably, the heterogeneity in the
      developmental origin of SP cells is reflected in their functional heterogeneity;
      somitically derived SP cells are intrinsically more myogenic than nonsomitically
      derived ones. Thus, we show that the somites, which supply embryonic and fetal
      myoblasts, are also an important source of highly myogenic adult muscle
      progenitors.

PMID- 16418264
TI  - Analysis of P53 mutations and their expression in 56 colorectal cancer cell
      lines.
AB  - A comprehensive analysis of the TP53 gene and its protein status was carried out
      on a panel of 56 colorectal cancer cell lines. This analysis was based on a
      combination of denaturing HPLC mutation screening of all exons of the p53 gene,
      sequencing the cDNA, and assessing the function of the p53 protein by assaying
      the induced expression of phosphorylated p53 and p21 after exposing cells to
      gamma-rays. In a few cases where there was no production of p53 message nor
      evidence of functional p53 protein, all of the p53 exons were sequenced directly.
      Thirteen of the 56 cell lines had functional p53, 21 lines had missense mutations
      (one of which made no detectable protein), 4 lines produced no p53 transcripts,
      and the remaining 18 lines carried truncating TP53 mutations. Thus, our results
      showed a relatively high frequency of TP53 mutations (76.8%) in our cell lines,
      with almost half of the mutations being truncating mutations. This is a rather
      higher frequency of such mutations than usually reported. Of the 18 cell lines
      with truncating mutations, 12 had detectable truncated protein based on Western
      blot analysis, whereas no protein was detected in the remaining 6 cell lines. Our
      data provide a valuable source of TP 53 mutations for further studies and raise
      the question of the extent to which truncating mutations may have dominant
      negative effects, even when no truncated protein can be detected by standard
      methods.

PMID- 16418265
TI  - Early auditory experience generates long-lasting memories that may subserve vocal
      learning in songbirds.
AB  - In both humans and songbirds, infants learn vocalizations by imitating the sounds
      of adult tutors with whom they interact during an early sensitive period. Vocal
      learning occurs in few animal taxa; similarities in the imitation process between
      humans and songbirds make the songbird a unique system in which vocal learning
      mechanisms can be studied at the neurobiological level. One theory of vocal
      learning proposes that early auditory experience generates auditory memories that
      subsequently guide vocal imitation. We now present a combination of behavioral
      and neurophysiological results, obtained in a songbird, that support this theory.
      We show that neurons in a forebrain auditory area of adult male zebra finches are
      selectively tuned to the song of a tutor heard early in development. Furthermore,
      the strength of this selectivity shows a striking correlation with the fidelity
      of vocal imitation, suggesting that this auditory memory may have served as the
      model for song learning.

PMID- 16418266
TI  - Gene expression profiles in acute myeloid leukemia with common translocations
      using SAGE.
AB  - Identification of the specific cytogenetic abnormality is one of the critical
      steps for classification of acute myeloblastic leukemia (AML) which influences
      the selection of appropriate therapy and provides information about disease
      prognosis. However at present, the genetic complexity of AML is only partially
      understood. To obtain a comprehensive, unbiased, quantitative measure, we
      performed serial analysis of gene expression (SAGE) on CD15(+) myeloid progenitor
      cells from 22 AML patients who had four of the most common translocations, namely
      t(8;21), t(15;17), t(9;11), and inv(16). The quantitative data provide clear
      evidence that the major change in all these translocation-carrying leukemias is a
      decrease in expression of the majority of transcripts compared with normal
      CD15(+) cells. From a total of 1,247,535 SAGE tags, we identified 2,604
      transcripts whose expression was significantly altered in these leukemias
      compared with normal myeloid progenitor cells. The gene ontology of the 1,110
      transcripts that matched known genes revealed that each translocation had a
      uniquely altered profile in various functional categories including regulation of
      transcription, cell cycle, protein synthesis, and apoptosis. Our global analysis
      of gene expression of common translocations in AML can focus attention on the
      function of the genes with altered expression for future biological studies as
      well as highlight genes/pathways for more specifically targeted therapy.

PMID- 16418261
TI  - DNA barcodes distinguish species of tropical Lepidoptera.
AB  - Although central to much biological research, the identification of species is
      often difficult. The use of DNA barcodes, short DNA sequences from a standardized
      region of the genome, has recently been proposed as a tool to facilitate species
      identification and discovery. However, the effectiveness of DNA barcoding for
      identifying specimens in species-rich tropical biotas is unknown. Here we show
      that cytochrome c oxidase I DNA barcodes effectively discriminate among species
      in three Lepidoptera families from Area de Conservacion Guanacaste in
      northwestern Costa Rica. We found that 97.9% of the 521 species recognized by
      prior taxonomic work possess distinctive cytochrome c oxidase I barcodes and that
      the few instances of interspecific sequence overlap involve very similar species.
      We also found two or more barcode clusters within each of 13 supposedly single
      species. Covariation between these clusters and morphological and/or ecological
      traits indicates overlooked species complexes. If these results are general, DNA
      barcoding will significantly aid species identification and discovery in tropical
      settings.

PMID- 16418267
TI  - Defining the sequence-recognition profile of DNA-binding molecules.
AB  - Determining the sequence-recognition properties of DNA-binding proteins and small
      molecules remains a major challenge. To address this need, we have developed a
      high-throughput approach that provides a comprehensive profile of the binding
      properties of DNA-binding molecules. The approach is based on displaying every
      permutation of a duplex DNA sequence (up to 10 positional variants) on a
      microfabricated array. The entire sequence space is interrogated simultaneously,
      and the affinity of a DNA-binding molecule for every sequence is obtained in a
      rapid, unbiased, and unsupervised manner. Using this platform, we have determined
      the full molecular recognition profile of an engineered small molecule and a
      eukaryotic transcription factor. The approach also yielded unique insights into
      the altered sequence-recognition landscapes as a result of cooperative assembly
      of DNA-binding molecules in a ternary complex. Solution studies strongly
      corroborated the sequence preferences identified by the array analysis.

PMID- 16418268
TI  - HIV-1 protease flaps spontaneously open and reclose in molecular dynamics
      simulations.
AB  - We report unrestrained, all-atom molecular dynamics simulations of HIV-1 protease
      that sample large conformational changes of the active site flaps. In particular,
      the unliganded protease undergoes multiple conversions between the "closed" and
      "semiopen" forms observed in crystal structures of inhibitor-bound and unliganded
      protease, respectively, including reversal of flap "handedness." Simulations in
      the presence of a cyclic urea inhibitor yield stable closed flaps. Furthermore,
      we observe several events in which the flaps of the unliganded protease open to a
      much greater degree than observed in crystal structures and subsequently return
      to the semiopen state. Our data strongly support the hypothesis that the
      unliganded protease predominantly populates the semiopen conformation, with
      closed and fully open structures being a minor component of the overall ensemble.
      The results also provide a model for the flap opening and closing that is
      considered to be essential to enzyme function.

PMID- 16418269
TI  - SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites
      in complex protein mixtures.
AB  - Reversible addition of NO to Cys-sulfur in proteins, a modification termed S
      nitrosylation, has emerged as a ubiquitous signaling mechanism for regulating
      diverse cellular processes. A key first-step toward elucidating the mechanism by
      which S-nitrosylation modulates a protein's function is specification of the
      targeted Cys (SNO-Cys) residue. To date, S-nitrosylation site specification has
      been laboriously tackled on a protein-by-protein basis. Here we describe a high
      throughput proteomic approach that enables simultaneous identification of SNO-Cys
      sites and their cognate proteins in complex biological mixtures. The approach,
      termed SNOSID (SNO Site Identification), is a modification of the biotin-swap
      technique [Jaffrey, S. R., Erdjument-Bromage, H., Ferris, C. D., Tempst, P. &
      Snyder, S. H. (2001) Nat. Cell. Biol. 3, 193-197], comprising biotinylation of
      protein SNO-Cys residues, trypsinolysis, affinity purification of biotinylated
      peptides, and amino acid sequencing by liquid chromatography tandem MS. With this
      approach, 68 SNO-Cys sites were specified on 56 distinct proteins in S
      nitrosoglutathione-treated (2-10 microM) rat cerebellum lysates. In addition to
      enumerating these S-nitrosylation sites, the method revealed endogenous SNO-Cys
      modification sites on cerebellum proteins, including alpha-tubulin, beta-tubulin,
      GAPDH, and dihydropyrimidinase-related protein-2. Whereas these endogenous SNO
      proteins were previously recognized, we extend prior knowledge by specifying the
      SNO-Cys modification sites. Considering all 68 SNO-Cys sites identified, a
      machine learning approach failed to reveal a linear Cys-flanking motif that
      predicts stable transnitrosation by S-nitrosoglutathione under test conditions,
      suggesting that undefined 3D structural features determine S-nitrosylation
      specificity. SNOSID provides the first effective tool for unbiased elucidation of
      the SNO proteome, identifying Cys residues that undergo reversible S
      nitrosylation.

PMID- 16418271
TI  - Heterogeneity in a room-temperature ionic liquid: persistent local environments
      and the red-edge effect.
AB  - In this work, we investigate the slow dynamics of 1-butyl-3-methylimidazolium
      hexafluorophosphate, a very popular room-temperature ionic solvent. Our study
      predicts the existence of heterogeneity in the liquid and shows that this
      heterogeneity is the underlying microscopic cause for the recently reported "red
      edge effect" (REE) observed in the study of fluorescence of the organic probe 2
      amino-7-nitrofluorene. This theoretical work explains in microscopic terms the
      relation between REE and dynamic heterogeneity in a room-temperature ionic liquid
      (IL). The REE is typical of micellar or colloidal systems, which are
      characterized by microscopic environments that are structurally very different.
      In contrast, in the case of this room-temperature IL, the REE occurs because of
      the long period during which molecules are trapped in quasistatic local solvent
      cages. This trapping time, which is longer than the lifetime of the excited-state
      probe, together with the inability of the surroundings to adiabatically relax,
      induces a set of site-specific spectroscopic responses. Subensembles of
      fluorescent molecules associated with particular local environments absorb and
      emit at different frequencies. We describe in detail the absorption wavelength
      dependent emission spectra of 2-amino-7-nitrofluorene and show that this
      dependence on lambda(ex) is characteristic of the IL and, as is to be expected,
      is absent in the case of a normal solvent such as methanol.

PMID- 16418270
TI  - Structure of Pfu Pop5, an archaeal RNase P protein.
AB  - We have used NMR spectroscopy and x-ray crystallography to determine the three
      dimensional structure of PF1378 (Pfu Pop5), one of four protein subunits of
      archaeal RNase P that shares a homolog in the eukaryotic enzyme. RNase P is an
      essential and ubiquitous ribonucleoprotein enzyme required for maturation of
      tRNA. In bacteria, the enzyme's RNA subunit is responsible for cleaving the
      single-stranded 5' leader sequence of precursor tRNA molecules (pre-tRNA),
      whereas the protein subunit assists in substrate binding. Although in bacteria
      the RNase P holoenzyme consists of one large catalytic RNA and one small protein
      subunit, in archaea and eukarya the enzyme contains several (> or =4) protein
      subunits, each of which lacks sequence similarity to the bacterial protein. The
      functional role of the proteins is poorly understood, as is the increased
      complexity in comparison to the bacterial enzyme. Pfu Pop5 has been directly
      implicated in catalysis by the observation that it pairs with PF1914 (Pfu Rpp30)
      to functionally reconstitute the catalytic domain of the RNA subunit. The protein
      adopts an alpha-beta sandwich fold highly homologous to the single-stranded RNA
      binding RRM domain. Furthermore, the three-dimensional arrangement of Pfu Pop5's
      structural elements is remarkably similar to that of the bacterial protein
      subunit. NMR spectra have been used to map the interaction of Pop5 with Pfu
      Rpp30. The data presented permit tantalizing hypotheses regarding the role of
      this protein subunit shared by archaeal and eukaryotic RNase P.

PMID- 16418272
TI  - Goalpha regulates olfactory adaptation by antagonizing Gqalpha-DAG signaling in
      Caenorhabditis elegans.
AB  - The heterotrimeric G protein G(o) is abundantly expressed in the mammalian
      nervous system and modulates neural activities in response to various ligands.
      However, G(o)'s functions in living animals are less well understood. Here, we
      demonstrate that GOA-1 G(o)alpha has a fundamental role in olfactory adaptation
      in Caenorhabditis elegans. Impairment of GOA-1 G(o)alpha function and excessive
      activation of EGL-30 G(q)alpha cause a defect in adaptation to AWC-sensed
      odorants. These pathways antagonistically modulate olfactory adaptation in AWC
      chemosensory neurons. Wild-type animals treated with phorbol esters and double
      mutant animals of diacylglycerol (DAG) kinases, dgk-3; dgk-1, also have a defect
      in adaptation, suggesting that elevated DAG signals disrupt normal adaptation.
      Constitutively active GOA-1 can suppress the adaptation defect of dgk-3; dgk-1
      double mutants, whereas it fails to suppress the adaptation defect of animals
      with constitutively active EGL-30, implying that GOA-1 acts upstream of EGL-30 in
      olfactory adaptation. Our results suggest that down-regulation of EGL-30-DAG
      signaling by GOA-1 underlies olfactory adaptation and plasticity of chemotaxis.

PMID- 16418273
TI  - The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control
      replication termination of Saccharomyces cerevisiae.
AB  - Termination of replication forks at the natural termini of the rDNA of
      Saccharomyces cerevisiae is controlled in a sequence-specific and polar mode by
      the interaction of the Fob1p replication terminator protein with the tandem Ter
      sites located in the nontranscribed spacers. Here we show, by both 2D gel
      analyses and chromatin immunoprecipitations (ChIP), that there exists a second
      level of global control mediated by the intra-S-phase checkpoint protein complex
      of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity
      of the Rrm3p helicase ("sweepase"). The sweepase tends to release arrested forks
      presumably by the transient displacement of the Ter-bound Fob1p. Consistent with
      this mechanism, very few replication forks were arrested at the natural
      replication termini in the absence of the two checkpoint proteins. In the absence
      of the Rrm3p helicase, there was a slight enhancement of fork arrest at the Ter
      sites. Simultaneous deletions of the TOF1 (or CSM3), and the RRM3 genes restored
      fork arrest by removing both the fork-releasing and fork-protection activities.
      Other genes such as MRC1, WSS1, and PSY2 that are also involved in the MRC1
      checkpoint pathway were not involved in this global control. This observation
      suggests that Tof1p-Csm3p function differently from MRC1 and the other above
      mentioned genes. This mechanism is not restricted to the natural Ter sites but
      was also observed at fork arrest caused by the meeting of a replication fork with
      transcription approaching from the opposite direction.

PMID- 16418274
TI  - Postsynaptic TrkB signaling has distinct roles in spine maintenance in adult
      visual cortex and hippocampus.
AB  - In adult primary visual cortex (V1), dendritic spines are more persistent than
      during development. Brain-derived neurotrophic factor (BDNF) increases synaptic
      strength, and its levels rise during cortical development. We therefore asked
      whether postsynaptic BDNF signaling through its receptor TrkB regulates spine
      persistence in adult V1. This question has been difficult to address because most
      methods used to alter TrkB signaling in vivo affect cortical development or
      cannot distinguish between pre- and postsynaptic mechanisms. We circumvented
      these problems by employing transgenic mice expressing a dominant negative TrkB
      EGFP fusion protein in sparse pyramidal neurons of the adult neocortex and
      hippocampus, producing a Golgi-staining-like pattern. In adult V1, expression of
      dominant negative TrkB-EGFP resulted in reduced mushroom spine maintenance and
      synaptic efficacy, accompanied by an increase in long and thin spines and
      filopodia. In contrast, mushroom spine maintenance was unaffected in CA1,
      indicating that TrkB plays fundamentally different roles in structural plasticity
      in these brain areas.

PMID- 16418275
TI  - Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type
      dependent biophysical and pharmacological properties.
AB  - ATP-sensitive K(+) channels (K(ATP)) are an octameric complex of inwardly
      rectifying K(+) channels (Kir6.1 and Kir6.2) and sulfonylurea receptors (SUR1 and
      SUR2A/B), which are involved in several diseases. The tissue-selective expression
      of the subunits leads to different channels; however, the composition and role of
      the functional channel in native muscle fibers is not known. In this article, the
      properties of K(ATP) channels of fast-twitch and slow-twitch muscles were
      compared by combining patch-clamp experiments with measurements of gene
      expression. We found that the density of K(ATP) currents/area was muscle-type
      specific, being higher in fast-twitch muscles compared with the slow-twitch
      muscle. The density of K(ATP) currents/area was correlated with the level of
      Kir6.2 expression. SUR2A was the most abundant subunit expressed in all muscles,
      whereas the vascular SUR2B subunit was expressed but at lower levels. A
      significant expression of the pancreatic SUR1 was also found in fast-twitch
      muscles. Pharmacological experiments showed that the channel response to the SUR1
      agonist diazoxide, SUR2A/B agonist cromakalim, SUR1 antagonist tolbutamide, and
      the SUR1/SUR2A/B-antagonist glibenclamide matched the SURs expression pattern.
      Muscle-specific K(ATP) subunit compositions contribute to the physiological
      performance of different muscle fiber types and determine the pharmacological
      actions of drugs modulating K(ATP) activity in muscle diseases.

PMID- 16418276
TI  - Pbn1p: an essential endoplasmic reticulum membrane protein required for protein
      processing in the endoplasmic reticulum of budding yeast.
AB  - PBN1 was identified as a gene required for production of protease B (PrB)
      activity in Saccharomyces cerevisiae. PBN1 encodes an endoplasmic reticulum (ER)
      localized, type I membrane glycoprotein and is essential for cell viability. To
      study the essential function(s) of Pbn1p, we constructed a strain with PBN1 under
      control of the GAL promoter. Depletion of Pbn1p in this strain abrogates
      processing of the ER precursor forms of PrB, Gas1p, and Pho8p. Depletion of Pbn1p
      does not affect exit of proprotease A or procarboxypeptidase Y from the ER,
      indicating that Pbn1p is not required for global exit from the ER. Depleting
      Pbn1p leads to a significant increase in the unfolded protein response pathway,
      accompanied by an expansion of bulk ER membrane, indicating that there is a
      defect in protein folding in the ER. pbn1-1, a nonlethal allele of PBN1, displays
      synthetic lethality with the ero1-1 allele (ERO1 is required for oxidation in the
      ER) and synthetic growth defects with the cne1Delta allele (CNE1 encodes
      calnexin). ER-associated degradation of a lumenal substrate, CPY*, is blocked in
      the absence of Pbn1p. These results suggest that Pbn1p is required for proper
      folding and/or the stability of a subset of proteins in the ER. Thus, Pbn1p is an
      essential chaperone-like protein in the ER of yeast.

PMID- 16418277
TI  - SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 glutamate
      receptors in Caenorhabditis elegans.
AB  - Most rapid excitatory synaptic signaling in the brain is mediated by postsynaptic
      ionotropic glutamate receptors (iGluRs) that are gated open by the
      neurotransmitter glutamate. In Caenorhabditis elegans, sol-1 encodes a CUB-domain
      transmembrane protein that is required for currents that are mediated by the GLR
      1 iGluR. Mutations in sol-1 do not affect GLR-1 expression, localization,
      membrane insertion, or stabilization at synapses, suggesting that SOL-1 is
      required for iGluR function. Here, we provide evidence that SOL-1 is an auxiliary
      subunit that modulates the gating of GLR-1 receptors. We show that mutant
      variants of GLR-1 with altered gating partially restore glutamate-gated current
      and GLR-1-dependent behaviors in sol-1 mutants. Domain analysis of SOL-1
      indicates that extracellular CUB domain 3 is required for function and that a
      secreted variant partially restores glutamate-gated currents and behavior. Also,
      we show that endogenous glutamatergic synaptic currents are absent in sol-1
      mutants. Our data suggest that GLR-1 iGluRs are not simply stand-alone molecules
      and require the SOL-1 auxiliary protein to promote the open state of the
      receptor. Our analysis presents the possibility that glutamatergic signaling in
      other organisms may be similarly modified by SOL-1-like transmembrane proteins.

PMID- 16418278
TI  - Label-free detection of DNA hybridization using carbon nanotube network field
      effect transistors.
AB  - We report carbon nanotube network field-effect transistors (NTNFETs) that
      function as selective detectors of DNA immobilization and hybridization. NTNFETs
      with immobilized synthetic oligonucleotides have been shown to specifically
      recognize target DNA sequences, including H63D single-nucleotide polymorphism
      (SNP) discrimination in the HFE gene, responsible for hereditary hemochromatosis.
      The electronic responses of NTNFETs upon single-stranded DNA immobilization and
      subsequent DNA hybridization events were confirmed by using fluorescence-labeled
      oligonucleotides and then were further explored for label-free DNA detection at
      picomolar to micromolar concentrations. We have also observed a strong effect of
      DNA counterions on the electronic response, thus suggesting a charge-based
      mechanism of DNA detection using NTNFET devices. Implementation of label-free
      electronic detection assays using NTNFETs constitutes an important step toward
      low-cost, low-complexity, highly sensitive and accurate molecular diagnostics.

PMID- 16418279
TI  - Reproductive protein protects functionally sterile honey bee workers from
      oxidative stress.
AB  - Research on aging shows that regulatory pathways of fertility and senescence are
      closely interlinked. However, evolutionary theories on social species propose
      that lifelong care for offspring can shape the course of senescence beyond the
      restricted context of reproductive capability. These observations suggest that
      control circuits of aging are remodeled in social organisms with continuing care
      for offspring. Here, we studied a circuit of aging in the honey bee (Apis
      mellifera). The bee is characterized by the presence of a long-lived reproductive
      queen caste and a shorter-lived caste of female workers that are life-long
      alloparental care givers. We focus on the role of the conserved yolk precursor
      gene vitellogenin that, in Caenorhabditis elegans, shortens lifespan as a
      downstream element of the insulin/insulin-like growth factor signaling cascade.
      Vitellogenin protein is synthesized at high levels in honey bee queens and is
      abundant in long-lived workers. We establish that vitellogenin gene activity
      protects worker bees from oxidative stress. Our finding suggests that one
      mechanistic explanation for patterns of longevity in bees is that a reproductive
      regulatory pathway has been remodeled to extend life. This perspective is of
      considerable relevance to research on longevity regulation that builds largely on
      inference from solitary model species.

PMID- 16418280
TI  - IA-2beta, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated
      insulin secretion.
AB  - Ghrelin is a newly discovered peptide and an endogenous ligand for growth hormone
      (GH) secretagogue (GHS) receptor. It has been shown to possess various central
      and peripheral effects, including GH secretion, food intake, and gastric and
      cardiac effects. Ghrelin and the GHS receptor are expressed also in pancreatic
      islets. We have identified several ghrelin-induced genes by PCR-select
      subtraction methods, among which is a beta-cell autoantigen for type 1 diabetes,
      IA-2beta. Administration of ghrelin increased IA-2beta mRNA in mouse brain,
      pancreas, and insulinoma cell lines (MIN6 and betaTC3). However, the expression
      of IA-2, another structurally related beta-cell autoantigen, was not induced by
      ghrelin. Administration of ghrelin or overexpression of IA-2beta, but not
      overexpression of IA-2, inhibited glucose-stimulated insulin secretion in MIN6
      insulinoma cells and, moreover, inhibition of IA-2beta expression by the RNA
      interference technique ameliorated ghrelin's inhibitory effects on glucose
      stimulated insulin secretion. These findings strongly suggest that inhibitory
      effects of ghrelin on glucose-stimulated insulin secretion are at least partly
      due to increased expression of IA-2beta induced by ghrelin. Our data demonstrate
      the link among ghrelin, IA-2beta, and glucose-stimulated insulin secretion.

PMID- 16418281
TI  - (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular
      function in humans.
AB  - Epidemiological and medical anthropological investigations suggest that flavanol
      rich foods exert cardiovascular health benefits. Endothelial dysfunction, a
      prognostically relevant key event in atherosclerosis, is characterized by a
      decreased bioactivity of nitric oxide (NO) and impaired flow-mediated
      vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol
      rich cocoa was associated with acute elevations in levels of circulating NO
      species, an enhanced FMD response of conduit arteries, and an augmented
      microcirculation. In addition, the concentrations and the chemical profiles of
      circulating flavanol metabolites were determined, and multivariate regression
      analyses identified (-)-epicatechin and its metabolite, epicatechin-7-O
      glucuronide, as independent predictors of the vascular effects after flavanol
      rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile
      and concentration of circulating flavanol compounds in plasma after cocoa
      ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo,
      thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced
      relaxation, as well as the in vivo increases in FMD, were abolished by inhibition
      of NO synthase. Oral administration of chemically pure (-)-epicatechin to humans
      closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the
      concept that a chronic intake of high-flavanol diets is associated with
      prolonged, augmented NO synthesis is supported by data that indicate a
      correlation between the chronic consumption of a cocoa flavanol-rich diet and the
      augmented urinary excretion of NO metabolites. Collectively, our data demonstrate
      that the human ingestion of the flavanol (-)-epicatechin is, at least in part,
      causally linked to the reported vascular effects observed after the consumption
      of flavanol-rich cocoa.

PMID- 16418282
TI  - Detachment of affinity-captured bioparticles by elastic deformation of a
      macroporous hydrogel.
AB  - Adsorption of bioparticles to affinity surfaces involves polyvalent interactions,
      complicating greatly the recovery of the adsorbed material. A unique system for
      the efficient binding and release of different cells and particles is described.
      Affinity-bound bioparticles and synthetic particles are detached from the
      macroporous hydrogel matrix, a so-called cryogel, when the cryogel undergoes
      elastic deformation. The particle detachment upon elastic deformation is believed
      to be due to breaking of many of the multipoint attachments between the particles
      and the affinity matrix and the change in the distance between affinity ligands
      when the matrix is deformed. However, no release of affinity-bound protein
      occurred upon elastic deformation. The phenomenon of particle detachment upon
      elastic deformation is believed to be of a generic nature, because it was
      demonstrated for a variety of bioparticles of different sizes and for synthetic
      particles, for different ligand-receptor pairs (IgG-protein A, sugar-ConA, metal
      ion-chelating ligand), and when the deformation was caused by either external
      forces (mechanical deformation) or internal forces (the shrinkage of
      thermosensitive, macroporous hydrogel upon an increase in temperature). The
      elasticity of cryogel monoliths ensures high recovery of captured cells under
      mild conditions, with highly retained viability. This property, along with their
      continuous porous structure makes cryogel monoliths very attractive for
      applications in affinity cell separation.

PMID- 16418283
TI  - Activation of protein C by the thrombin-thrombomodulin complex: cooperative roles
      of Arg-35 of thrombin and Arg-67 of protein C.
AB  - The binding of Ca(2+) to the 70-80 loop of protein C inhibits protein C
      activation by thrombin in the absence of thrombomodulin (TM), but the metal ion
      is required for activation in the presence of TM. Structural data suggests that
      the 70-80 loop is located between two antiparallel beta strands comprised of
      residues 64-69 and 81-91 on the protease domain of protein C. To test the
      hypothesis that a salt-bridge/hydrogen bond interaction between Arg-67 of the
      former strand and Asp-82 of the latter strand modulates the unique Ca(2+)-binding
      properties of protein C, we engineered a disulfide bond between the two strands
      by substituting both Arg-67 and Asp-82 with Cys residues. The activation of this
      mutant was enhanced 40- to 50-fold independent of TM and Ca(2+). Furthermore, the
      Arg-67 to Ala mutant of protein C was activated in the absence of TM by the Arg
      35 to Glu mutant of thrombin with the same efficiency as wild-type protein C by
      wild-type thrombin-TM complex. These results suggest that TM functions by
      alleviating the Ca(2+)-dependent inhibitory interactions of Arg-67 of protein C
      and Arg-35 of thrombin.

PMID- 16418284
TI  - Pollination decays in biodiversity hotspots.
AB  - As pollinators decline globally, competition for their services is expected to
      intensify, and this antagonism may be most severe where the number of plant
      species is the greatest. Using meta-analysis and comparative phylogenetic
      analysis, we provide a global-scale test of whether reproduction becomes more
      limited by pollen receipt (pollen limitation) as the number of coexisting plant
      species increases. As predicted, we find a significant positive relationship
      between pollen limitation and species richness. In addition, this pattern is
      particularly strong for species that are obligately outcrossing and for trees
      relative to herbs or shrubs. We suggest that plants occurring in species-rich
      communities may be more prone to pollen limitation because of interspecific
      competition for pollinators. As a consequence, plants in biodiversity hotspots
      may have a higher risk of extinction and/or experience increased selection
      pressure to specialize on certain pollinators or diversify into different
      phenological niches. The combination of higher pollen limitation and habitat
      destruction represents a dual risk to tropical plant species that has not been
      previously identified.

PMID- 16418285
TI  - Osmotic effects on vacuolar ion release in guard cells.
AB  - Tracer flux experiments in isolated guard cells of Commelina communis L. suggest
      that the vacuolar ion content is regulated and is reset to a reduced fixed point
      by abscisic acid (ABA) with no significant change in cytoplasmic content. The
      effects of changes in external osmotic pressure were investigated by adding and
      removing mannitol from the bathing solution. Two effects were distinguished. In
      the new steady state of volume and turgor, the vacuolar ion efflux was sensitive
      to turgor: efflux increased at high turgor and reduced at lower turgor after the
      addition of mannitol. These changes were inhibited by phenylarsine oxide and are
      likely to involve the same channel that is involved in the response to ABA. After
      a hypoosmotic transfer, there was an additional effect: a fast transient
      stimulation of vacuolar efflux during the period of water flow into the cell; the
      size of this hypopeak increased with the size of the hypoosmotic shock, with
      increased water flow. No corresponding transient in reduced vacuolar efflux was
      observed upon hyperosmotic transfer. The fast hypopeak was not inhibited by
      phenylarsine oxide and appears to involve a different ion channel from that
      involved in the resting efflux, the response to ABA, or the turgor sensitivity.
      Thus, the tonoplast can sense an osmotic gradient and respond to water flow into
      the vacuole by increased vacuolar ion efflux, thereby minimizing cytoplasmic
      dilution. An aquaporin is the most likely sensor and may also be involved in the
      signal transduction chain.

PMID- 16418287
TI  - Early maize (Zea mays L.) cultivation in Mexico: dating sedimentary pollen
      records and its implications.
AB  - A sedimentary pollen sequence from the coastal plain of Veracruz, Mexico,
      demonstrates maize cultivation by 5,000 years ago, refining understanding of the
      geography of early maize cultivation. Methodological issues related to
      bioturbation involved in dating that record combine with its similarity to a
      pollen sequence from the coastal plain of Tabasco, Mexico, to suggest that the
      inception of maize cultivation in that record occurred as much as 1,000-2,000
      years more recently than the previously accepted 7,000 years ago. Our analysis
      thereby has substantive, theoretical, and methodological implications for
      understanding the complex process of maize domestication. Substantively, it
      demonstrates that the earliest securely dated evidence of maize comes from
      macrofossils excavated near Oaxaca and Tehuacan, Mexico, and not from the coastal
      plain along the southern Gulf of Mexico. Theoretically, that evidence best
      supports the hypothesis that people in the Southern Highlands domesticated this
      important crop plant. Methodologically, sedimentary pollen and other microfossil
      sequences can make valuable contributions to reconstructing the geography of
      early maize cultivation, but we must acknowledge the limits to precision that
      bioturbation in coastal lagoons imposes on the dating of such records.

PMID- 16418286
TI  - ES cells derived from cloned and fertilized blastocysts are transcriptionally and
      functionally indistinguishable.
AB  - Reproductive cloning is uniformly rejected as a valid technology in humans
      because of the severely abnormal phenotypes seen in cloned animals. Gene
      expression aberrations observed in tissues of cloned animals have also raised
      concerns regarding the therapeutic application of "customized" embryonic stem
      (ES) cells derived by nuclear transplantation (NT) from a patient's somatic
      cells. Although previous experiments in mice have demonstrated that the
      developmental potential of ES cells derived from cloned blastocysts (NT-ES cells)
      is identical to that of ES cells derived from fertilized blastocysts, a
      systematic molecular characterization of NT-ES cell lines is lacking. To
      investigate whether transcriptional aberrations, similar to those observed in
      tissues of cloned mice, also occur in NT-ES cells, we have compared
      transcriptional profiles of 10 mouse NT- and fertilization-derived-ES cell lines.
      We report here that the ES cell lines derived from cloned and fertilized mouse
      blastocysts are indistinguishable based on their transcriptional profiles,
      consistent with their normal developmental potential. Our results indicate that,
      in contrast to embryonic and fetal development of clones, the process of NT-ES
      cell derivation rigorously selects for those immortal cells that have erased the
      "epigenetic memory" of the donor nucleus and, thus, become functionally
      equivalent. Our findings support the notion that ES cell lines derived from
      cloned or fertilized blastocysts have an identical therapeutic potential.

PMID- 16418288
TI  - Up, down, and all around: how plants sense and respond to environmental stimuli.

PMID- 16418289
TI  - A virus-specific CD8+ T cell immunodominance hierarchy determined by antigen dose
      and precursor frequencies.
AB  - Immunodominance hierarchies are a substantial, but poorly understood,
      characteristic of CD8(+) T cell-mediated immunity. Factors influencing the
      differential responses to the influenza A virus nucleoprotein (NP(366-374)) and
      acid polymerase (PA(224-233)) peptides presented by H2D(b) have been analyzed by
      disabling (N5--> Q substitution) these peptides in their native configuration,
      then expressing them in the viral neuraminidase protein. This strategy of
      shifting epitopes within the same viral context resulted in an apparent
      equalization of D(b)NP(366) [epitope consisting of viral nucleoprotein (NP) amino
      acid residues 366-374 complexed with the H2D(b) MHC class I glycoprotein] and
      D(b)PA(224) (H2D(b)+PA(224-233)) epitope abundance after direct infection in
      vitro and induced reproducible changes in the magnitude of the D(b)NP(366)- and
      D(b)PA(224)-specific T cell subsets generated after infection of mice. Comparison
      of D(b)NP(366)- and D(b) PA(224)-specific CD8(+) T cell responses induced from
      the native configuration and from the viral neuraminidase stalk demonstrated that
      the size of both primary and secondary responses is influenced by relative
      epitope levels and that, at least after secondary challenge, the magnitude of
      responses is also determined by CD8(+) T cell precursor frequency. Thus, this
      immunodominance hierarchy is a direct function of antigen dose and T cell
      numbers.

PMID- 16418291
TI  - High biological species diversity in the arctic flora.
AB  - The arctic flora is considered to be impoverished, but estimates of species
      diversity are based on morphological assessments, which may not provide accurate
      counts of biological species. Here we report on crossing relationships within
      three diploid circumpolar plant species in the genus Draba (Brassicaceae).
      Although 99% of parental individuals were fully fertile, the fertility of
      intraspecific crosses was surprisingly low. Hybrids from crosses within
      populations were mostly fertile (63%), but only 8% of the hybrids from crosses
      within and among geographic regions (Alaska, Greenland, Svalbard, and Norway)
      were fertile. The frequent occurrence of intraspecific crossing barriers is not
      accompanied by significant morphological or ecological differentiation,
      indicating that numerous cryptic biological species have arisen within each
      taxonomic species despite their recent (Pleistocene) origin.

PMID- 16418290
TI  - Caspase recruitment domain protein 6 is a microtubule-interacting protein that
      positively modulates NF-kappaB activation.
AB  - Proteins containing a caspase recruitment domain (CARD) play pivotal roles in
      signal transduction leading to apoptosis and NF-kappaB activation and
      inflammation. Here we identify and characterize human and mouse CARD protein 6
      (CARD6), CARD-containing proteins of unique structure. CARD6 associates with
      microtubules and interacts with receptor-interacting protein (RIP)-like
      interacting caspase-like apoptosis regulatory protein kinase (RICK), a CARD
      containing member of the RIP family of protein kinases. These kinases are
      involved in multiple NF-kappaB signaling pathways important for innate and
      adaptive immune responses. Surprisingly, the CARDs of CARD6 and RICK were not
      required for their interaction; instead, mutational analysis revealed that the
      CARD of CARD6 negatively controls the association of these molecules. CARD6 also
      binds to RIP1, a RIP kinase homologue that lacks a CARD but contains a C-terminal
      death domain. Coexpression of RICK targets CARD6 to aggresomes via a mechanism
      that requires the CARD of RICK. Importantly, CARD6 expression has a synergistic
      effect on NF-kappaB activation induced by several independent signal transduction
      pathways. In summary, our results indicate that CARD6 is a regulator of NF-kappaB
      activation that modulates the functions of RIP kinase family members.

PMID- 16418292
TI  - Antibodies selected from combinatorial libraries block a tumor antigen that plays
      a key role in immunomodulation.
AB  - We searched for cell-surface-associated proteins overexpressed on B cell chronic
      lymphocytic leukemia (CLL) to use as therapeutic antibody targets. Antibodies
      binding the immunosuppressive molecule CD200 were identified by cell panning of
      an antibody phage display library derived from rabbits immunized with primary CLL
      cells. B cells from 87 CLL patients exhibited 1.6- to 5.4-fold cell-surface up
      regulation of CD200 relative to normal B cells. An effect of increased CD200
      expression by CLL cells on the immune system was evaluated in mixed lymphocyte
      reactions. Addition of primary CLL but not normal B cells to macrophages and T
      cells downregulated the Th1 response, as seen by a 50-95% reduction in secreted
      IL-2 and IFN-gamma. Antibodies to CD200 prevented downregulation of the Th1
      response in most B cell CLL samples evaluated, indicating abrogation of the
      CD200/CD200R interaction can be sufficient to restore the Th1 response. A disease
      progression-associated shift of the immune response from Th1 to Th2 has been
      observed in numerous cancers. Because this cytokine shift is also believed to
      promote the induction of regulatory T cells, reverting the immune response to Th1
      through direct targeting of the cancer cells may provide therapeutic benefits in
      CLL by encouraging a cytotoxic T cell response.

PMID- 16418293
TI  - Morphological homeostasis in cortical dendrites.
AB  - Neurons have significant potential for the homeostatic regulation of a broad
      range of functional features, from gene expression to synaptic excitability. In
      this article, we show that dendritic morphology may also be under intrinsic
      homeostatic control. We present the results from a statistical analysis of a
      large collection of digitally reconstructed neurons, demonstrating that
      fluctuations in dendritic size in one given portion of a neuron are
      systematically counterbalanced by the remaining dendrites in the same cell. As a
      result, the total dendritic measure (e.g., number of branches, length, and
      surface area) of each neuron in a given morphological class is, on average,
      significantly less random than would be expected if trees (and their parts) were
      regulated independently during development. This observation is general across
      scales that range from gross basal/apical subdivisions to individual branches and
      bifurcations, and its statistical significance is robust among various brain
      regions, cell types, and experimental conditions. Given the pivotal dendritic
      role in signal integration, synaptic plasticity, and network connectivity, these
      findings add a dimension to the functional characterization of neuronal
      homeostasis.

PMID- 16418294
TI  - Serotonergic neuron diversity: identification of raphe neurons with discharges
      time-locked to the hippocampal theta rhythm.
AB  - The serotonergic system plays a key role in the regulation of brain states, and
      many of the known features of serotonergic neurons appear to match this function.
      Midbrain raphe nuclei provide a diffuse projection to all regions of the
      forebrain, and raphe neurons exhibit a slow metronome-like activity that sets the
      ambient levels of serotonin across the sleep-wake cycle. Serotonergic cells have
      also been implicated, however, in a variety of more specific functions that can
      hardly be related to their low-rate monotonous patterns of discharges. The
      amazing variety of serotonergic receptors and their type-specific distribution on
      cortical neurons also raise the possibility of a more intimate coordination
      between the activity of serotonergic neurons and their target cortical circuits.
      Here we report an unexpected diversity in the behavior of immunohistochemically
      identified serotonergic neurons. Two outstanding subpopulations were identified
      by using the in vivo juxtacellular recording and labeling technique. The first
      subpopulation of serotonergic cells exhibited the classic clock-like activity
      with no apparent short timescale interaction with the hippocampal
      electroencephalogram. The other subpopulation discharged action potentials that
      were phase-locked to the hippocampal theta rhythm, the oscillatory pattern
      associated with acquisition of information and memory formation. These results
      indicate that the ascending serotonergic system comprises cells involved in
      complex information processing beyond the regulation of state transitions. The
      heterogeneity of serotonergic neuron behavior can also help to explain the
      complexity of symptoms associated with serotonergic dysfunction.

PMID- 16418295
TI  - The products of a single maize sesquiterpene synthase form a volatile defense
      signal that attracts natural enemies of maize herbivores.
AB  - Plants can defend themselves against herbivores by attracting natural enemies of
      the herbivores. The cues for attraction are often complex mixtures of herbivore
      induced plant volatiles, making it difficult to demonstrate the role of specific
      compounds. After herbivory by lepidopteran larvae, maize releases a mixture of
      volatiles that is highly attractive to females of various parasitic wasp species.
      We identified the terpene synthase TPS10 that forms (E)-beta-farnesene, (E)-alpha
      bergamotene, and other herbivory-induced sesquiterpene hydrocarbons from the
      substrate farnesyl diphosphate. The corresponding gene is expressed in response
      to herbivore attack and is regulated at the transcript level. Overexpression of
      tps10 in Arabidopsis thaliana resulted in plants emitting high quantities of
      TPS10 sesquiterpene products identical to those released by maize. Using these
      transgenic Arabidopsis plants as odor sources in olfactometer assays showed that
      females of the parasitoid Cotesia marginiventris learn to exploit the TPS10
      sesquiterpenes to locate their lepidopteran hosts after prior exposure to these
      volatiles in association with hosts. This dissection of the herbivore-induced
      volatile blend demonstrates that a single gene such as tps10 can be sufficient to
      mediate the indirect defense of maize against herbivore attack.

PMID- 16418296
TI  - Stat5a/b are essential for normal lymphoid development and differentiation.
AB  - Cytokines that use the common gamma chain gammac are critical for lymphoid
      development and function. Mutations of the IL-7 receptor, gammac, or its
      associated kinase, Jak3, are the major cause of human severe combined
      immunodeficiency. Although activated by IL-7, Stat5a/b (Stat, signal transducer
      and activator of transcription) have been thought to play limited roles in
      lymphoid development. However, we now show that mice completely deficient in
      Stat5a/b have severely impaired lymphoid development and differentiation. Absence
      of Stat5 also abrogates T cell receptor gamma rearrangement and survival of
      peripheral CD8(+) T cells. Thus, deficiency of Stat5 results in severe combined
      immunodeficiency, similar in many respects to deficiency of IL-7R, gammac, and
      Jak3.

PMID- 16418298
TI  - Intrinsic kinetics determine the time course of neuronal synaptic transporter
      currents.
AB  - Efficient clearance of synaptically released glutamate from the extracellular
      space is an absolute requirement for maintaining information processing in the
      central nervous system. In the cerebellum, clearance of glutamate relies on
      uptake by Bergmann glial cells and Purkinje cells (PCs). Uptake by PCs can be
      monitored by recording the synaptic transport current (STC) mediated by the PC
      specific transporter excitatory amino acid transporter 4 (EAAT4). The slow time
      course of the PC STC has been used to argue that glutamate clearance is
      protracted. We find, however, that the time course of the STC is not affected by
      altering the amount of glutamate released at individual synapses or by partial
      transporter blockade, manipulations that would be expected to change the duration
      of the extracellular glutamate transient. Ion substitution experiments and
      kinetic modeling of the PC transporter current suggest that physiological levels
      of intracellular Na(+) and glutamate slow the cycling rate of transporters and
      thereby lengthen the time course of STCs. The model predicts that PC transporters
      bind glutamate quickly but that the actual cycling rate of EAAT4 in physiological
      conditions is slow; therefore, the STC reflects the intrinsic kinetics of the
      glutamate transporter, not the rate of glutamate clearance.

PMID- 16418297
TI  - Wnt3a gradient converts radial to bilateral feather symmetry via topological
      arrangement of epithelia.
AB  - The evolution of bilaterally symmetric feathers is a fundamental process leading
      toward flight. One major unsolved mystery is how the feathers of a single bird
      can form radially symmetric downy feathers and bilaterally symmetric flight
      feathers. In developing downy feather follicles, barb ridges are organized
      parallel to the long axis of the feather follicle. In developing flight-feather
      follicles, the barb ridges are organized helically toward the anterior region,
      leading to the fusion and creation of a rachis. Here we discover an anterior
      posterior molecular gradient of wingless int (Wnt3)a in flight but not downy
      feathers. Global inhibition of the Wnt gradient transforms bilaterally symmetric
      feathers into radially symmetric feathers. Production of an ectopic local Wnt3a
      gradient reoriented barb ridges toward the source and created an ectopic rachis.
      We further show that the orientation of the Wnt3a gradient is dictated by the
      dermal papilla (DP). Swapping DPs between wing covert and breast downy feathers
      demonstrates that both feather symmetry and molecular gradients are in accord
      with the origin of the DP. Thus the fates of feather epidermal cells are not
      predetermined through some molecular codes but can be modulated. Together, our
      data suggest feathers are shaped by a DP--> Wnt gradient-->helical barb ridge
      organization-->creation of rachis-->bilateral symmetry sequence. We speculate
      diverse feather forms can be achieved by adjusting the orientation and slope of
      molecular gradients, which then shape the topological arrangements of feather
      epithelia, thus linking molecular activities to organ forms and novel functions.

PMID- 16418299
TI  - Role of ATP in DNA synthesis of renal proximal tubule cells: involvement of
      calcium, MAPKs, and CDKs.
AB  - Although ATP has been shown to act as a modulator in various kidney functions,
      its effect on renal proximal tubule cell (PTC) proliferation has not been
      elucidated. This study investigated the effect of ATP on cell proliferation and
      the effect of its related signal pathways on primary cultured PTCs. Treatment
      with >10(-5) M ATP for 1 h stimulated incorporation of thymidine and
      bromodeoxyuridine. ATP (10(-4) M)-induced stimulation of thymidine incorporation
      was blocked by suramin (a P2X and P2Y receptor antagonist), reactive blue 2 (a
      P2Y receptor antagonist), MRS-2159 (a P2X1 receptor antagonist), and MRS-2179 (a
      P2Y1 receptor antagonist). ATP increased intracellular Ca2+ concentration, which
      was blocked by suramin, methoxyverapamil, and EGTA. ATP-induced stimulation of
      cell proliferation was also blocked by EGTA (an extracellular Ca2+ chelator),
      methoxyverapamil (a Ca2+ antagonist), and nifedipine (an L-type Ca2+ channel
      blocker), suggesting a role for Ca2+ influx. ATP-induced phosphorylation of p38
      and p44/42 MAPKs was blocked by nifedipine. ATP increased expression levels of
      cyclin-dependent kinase (CDK)-2, CDK-4, and cyclin E, which were blocked by
      suramin, reactive blue 2, MRS-2179, MRS-2159, and nifedipine. However, ATP
      decreased expression levels of p21WAF1/Cip1 and p27kip1. ATP-induced stimulation
      of thymidine incorporation and increase of CDK-2 and CDK-4 expression were
      blocked by SB-203580 (a p38 MAPK inhibitor) and PD-98059 (an MEK inhibitor), but
      not by SP-600125 (a JNK inhibitor). In conclusion, ATP stimulates proliferation
      by increasing intracellular Ca2+ concentration and activating p38, p44/42 MAPKs,
      and CDKs in PTCs.

PMID- 16418300
TI  - Levosimendan protects against experimental endotoxemic acute renal failure.
AB  - Endotoxemia induces a hemodynamic form of acute renal failure (ARF; renal
      vasoconstriction +/- reduced glomerular ultrafiltration coefficient, K(f);
      minimal/no histological damage). We tested whether levosimendan (LS), an ATP
      sensitive K+ (K(ATP)) channel opener with cardiac ionotropic and possible anti
      inflammatory properties, might have utility in combating this form of ARF. CD-1
      mice were injected with LPS +/- LS. LS effects on LPS-induced systemic
      inflammation (plasma TNF-alpha/MCP-1; cardiorenal mRNAs), plasma NO levels, and
      azotemia were assessed. Because K(ATP) channel opening has been reported to
      mediate hypoxic tubular injury, possible adverse LS effects on ischemic ARF and
      ATP depletion injury were sought. Effects of diazoxide (another K(ATP) channel
      agonist) and glibenclamide (a channel antagonist) on hypoxic tubular injury also
      were assessed. Finally, the ability of LS to alter rat mesangial cell (MC)
      contraction in response to ANG II (elevated in sepsis) was tested. LS conferred
      almost complete protection against LPS-induced ARF, without any apparent
      reduction in the LPS-induced inflammatory response. Neither LS nor diazoxide
      altered ATP depletion-mediated tubule injury (in vivo or in vitro). Conversely,
      glibenclamide induced a marked and direct cytotoxic effect. LS completely blocked
      ANG II-induced MC contraction, an action likely to increase K(f). We concluded
      that 1) LS can confer marked protection against LPS-induced ARF; 2) this likely
      stems from vasoactive properties, rather than reductions in LPS-induced
      inflammation; and 3) K(ATP) channel agonists (but not antagonists) appear to be
      devoid of toxic proximal tubular cell effects. This suggests that LS, and other
      K(ATP) channel agonists, have a margin of safety if employed in situations
      (sepsis syndrome, heart failure) in which severe renal vasoconstriction might
      lead to ischemic ARF.

PMID- 16418301
TI  - A1 adenosine receptor knockout mice are protected against acute radiocontrast
      nephropathy in vivo.
AB  - The role of renal A1 adenosine receptors (A1AR) in the pathogenesis of
      radiocontrast nephropathy is controversial. We aimed to further elucidate the
      role of A1AR in the pathogenesis of radiocontrast nephropathy and determine
      whether renal proximal tubule A1AR contribute to the radiocontrast nephropathy.
      To induce radiocontrast nephropathy, A1AR wild-type (WT) or knockout (KO) mice
      were injected with a nonionic radiocontrast (iohexol, 1.5-3 g iodine/kg). Some
      A1WT mice were pretreated with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a
      selective A1AR antagonist) before iohexol injection. A1AR contribute to the
      pathogenesis of radiocontrast nephropathy in vivo as the A1WT mice developed
      significantly worse acute renal failure, more renal cortex vacuolization, and had
      lower survival 24 h after iohexol treatment compared with the A1KO mice. DPCPX
      pretreatment also protected the A1WT mice against radiocontrast-induced acute
      renal failure. No differences in renal cortical apoptosis or inflammation were
      observed between A1WT and A1KO mice. To determine whether the proximal tubular
      A1AR mediate the direct renal cytotoxicity of radiocontrast, we treated proximal
      tubules in culture with iohexol with or without 2-chloro-N6-cyclopentyladenosine
      (a selective A1AR agonist) or DPCPX pretreatment. We also subjected cultured
      proximal tubule cells overexpressing A1AR or lacking A1AR to radiocontrast
      injury. Iohexol caused a direct dose-dependent reduction in proximal tubule cell
      viability as well as proliferation. Neither the A1AR agonist nor the antagonist
      treatment affected proximal tubule viability or proliferation. Moreover,
      overexpression or lack of A1AR failed to impact the iohexol toxicity on proximal
      tubule cells. Therefore, we conclude that radiocontrast causes acute renal
      failure via mechanisms dependent on A1AR; however, renal proximal tubule A1AR do
      not contribute to the direct tubular toxicity of radiocontrast.

PMID- 16418302
TI  - Expression of canonical transient receptor potential (TRPC) proteins in human
      glomerular mesangial cells.
AB  - Mesangial cells are located within glomerular capillary loops and contribute to
      the physiological regulation of glomerular hemodynamics. The function of
      mesangial cells is controlled by a variety of ion channels in the plasma
      membrane, including nonselective cation channels, receptor-operated Ca2+
      channels, and recently identified store-operated Ca2+ channels. Although the
      significance of these channels has been widely acknowledged, their molecular
      identities are still unknown. Recently, the members of the canonical transient
      receptor potential (TRPC) protein family have been demonstrated to behave as
      cation channels. The present study was performed to identify the isoforms of
      endogenous TRPC proteins in human mesangial cells (HMCs) and their interactions.
      Western blotting showed that TRPC1, 3, 4, and 6 were expressed in cultured HMCs.
      Consistently, immunofluorescent confocal microscopy revealed specific stainings
      for TRPC1, 3, 4, and 6 with predominant intracellular localization. However,
      TRPC5 and 7 were not detectable at protein level by either Western blotting or
      immunofluorescent staining. The expression of TRPC1, 3, 4, and 6 was also
      observed in rat and human glomeruli using fluorescent immunohistochemistry.
      Furthermore, coimmunoprecipitation experiments and immunofluorescent double
      staining displayed that TRPC1 had physical interaction with TRPC4 and 6, while no
      interactions were detected among other isoforms of TRPCs. Ca2+ fluorescent
      ratiometry measurement showed that store-operated Ca2+ entry in HMCs was
      significantly reduced by knocking down TRPC1, but enhanced by overexpressing
      TRPC1. These results suggest that HMCs specifically express isoforms of TRPC1, 3,
      4, and 6 proteins. These isoforms of TRPCs might selectively assemble to form
      functional complexes.

PMID- 16418303
TI  - Intrarenal octreotide treatment prevents sodium retention in liver cirrhotic
      rats: evidence for direct effects within the thick ascending limb of Henle's
      loop.
AB  - We have previously shown that systemic treatment with the somatostatin analog
      octreotide has marked beneficial effects on renal function in rats with liver
      cirrhosis induced by common bile duct ligation (CBL; Jonassen TEN, Christensen S,
      Sorensen AM, Marcussen N, Flyvbjerg A, Andreasen F, and Petersen JS. Hepatology
      29: 1387-1395, 1999). In the present study, we tested the hypothesis that
      octreotide has a direct effect on renal tubular function. Rats (CBL or Sham-CBL)
      were intrarenally treated with low-dose octreotide in a long-acting release
      formulation, which had no systemic actions (100 microg/kg body wt as a single
      dose). Rats receiving low-dose octreotide (sc) were used as controls. The rats
      were chronically instrumented, and renal function was examined 4 wk after CBL or
      Sham-CBL. Intrarenal octreotide administration (IROA) prevented sodium retention
      in CBL rats without changes in renal plasma flow, glomerular filtration rate, or
      circulating levels of aldosterone and vasopressin. Renal clearance studies
      revealed that IROA normalized the increased natriuretic efficacy of furosemide
      found in CBL rats. Furthermore, IROA protected against the development of
      hypertrophy of the inner stripe of the outer medulla and thereby the increased
      the volume of thick ascending limb of Henle's loop (TAL) epithelium found in CBL
      rats. Finally, Western blot analyses of outer medullary homogenates showed
      increased abundance of the furosemide-sensitive Na-K-2Cl (NKCC2) cotransporter.
      IROA did not affect the abundance of NCKK2 within the outer medulla. Together
      with the histological findings, these results indicate that IROA reduces the
      total number of NKCC2 within the outer medulla. In conclusion, the results
      indicate a direct intrarenal effect of octreotide on TAL function and morphology
      in cirrhotic rats.

PMID- 16418304
TI  - Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse.
AB  - AIMS: Although interleukin 8 (IL-8) is not produced in the normal cornea, it has
      been detected there in several pathological conditions. In this study, the direct
      effects of IL-8 overexpression on the cornea was examined. METHODS: The corneal
      surface of severe combined immunodeficiency mice was infected by the adenovirus
      vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were
      observed at various time points. RESULTS: Clinically, marked angiogenesis and
      ulcer formation in the cornea were observed by 12 hours and 24 hours,
      respectively. Histologically, prominent angiogenesis was observed in the corneal
      stroma at 12 hours. Cleft formation between the corneal epithelium and stroma,
      and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24
      hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the
      cornea. In contrast, infection with the control adenovirus carrying the beta
      galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil
      infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5
      resulted in the production of IL-8 by corneal and conjunctival stromal cells.
      CONCLUSION: Our results indicate that IL-8 overexpression in corneal tissue
      causes ulcer formation in the cornea through chemoattraction of neutrophils,
      suggesting the aetiological role of IL-8 in some types of corneal ulcers.

PMID- 16418305
TI  - Cerebrospinal fluid leucocyte counts in healthy neonates.
AB  - OBJECTIVES: To determine the cerebrospinal fluid (CSF) white blood cell (WBC)
      count of normal term neonates, and compare the CSF WBC profile of normal and
      symptomatic infants without infection of the central nervous system (CNS).
      METHOD: Neonates were included if (a) they were at risk of congenital Toxoplasma
      infection and had undergone a lumbar puncture to assess CNS involvement, and (b)
      serial specific serum IgG and IgM determinations had ruled out congenital
      infection. According to neonatal chart reviews, 30 consecutive patients without
      CNS infection were classified as normal (absolutely asymptomatic) or symptomatic
      (any kind of symptoms). RESULTS: CSF WBC count was higher in 11 symptomatic
      (7/mm(3), 0-30/mm(3)) than in 19 normal (1/mm(3), 0-5/mm(3)) neonates (p<0.01).
      CONCLUSION: Normal neonatal CSF contains up to 5 WBCs/mm(3). Mild pleocytosis can
      be found in symptomatic infants without CNS infection.

PMID- 16418306
TI  - Respiratory function of very prematurely born infants at follow up: influence of
      sex.
AB  - OBJECTIVE: To test the hypothesis that male compared with female prematurely born
      infants would have worse lung function at follow up. DESIGN: Prospective follow
      up study. SETTING: Tertiary neonatal intensive care units PATIENTS: Seventy six
      infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom
      oscillation study. INTERVENTIONS: Lung function measurements at a corrected age
      of 1 year. MAIN OUTCOME MEASURES: Airways resistance (Raw) and functional
      residual capacity (FRC(pleth)) measured by whole body plethysmography, specific
      conductance (sGaw) calculated from Raw and FRC(pleth), and FRC measured by a
      helium gas dilution technique (FRC(He)). RESULTS: The 42 male infants differed
      significantly from the 34 female infants in having a lower birth weight for
      gestation, requiring more days of ventilation, and a greater proportion being
      oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean
      Raw and FRC(pleth) were significantly higher and mean sGaw significantly lower.
      After adjustment for birth and current size differences, the sex differences in
      FRC(pleth) and sGaw were 15% and 26% respectively and remained significant.
      CONCLUSION: Lung function at follow up of prematurely born infants is influenced
      by sex.

PMID- 16418307
TI  - Higher long-term cancer survival rates in southeastern Netherlands using up-to
      date period analysis.
AB  - BACKGROUND: The aim was to compare long-term survival rates for different types
      of cancer estimated by means of up to date period analysis with those from more
      traditional cohort analysis. PATIENTS AND METHODS: Data from the Eindhoven Cancer
      Registry were used. In total 140,137 newly diagnosed patients diagnosed between
      1980 and 2002 and followed until 1 January 2005 were included. Five-, 10- and 20
      year relative survival rates were calculated. RESULTS: For total cancer in men
      and women, childhood cancer, rectal cancer, melanoma in women, breast cancer,
      prostate cancer and all leukaemias, much higher 10-year survival rates were found
      with period analyses (differences with cohort analyses were 5.1%, 3.6%, 7.4%,
      5.6%, 6.5%, 4.0%, 5.1% and 10.5%, respectively). For laryngeal and bladder cancer
      the 10-year survival rates estimated with period analyses were about 7.5% lower
      compared with those estimated by means of cohort analyses. CONCLUSIONS: Period
      analysis, based on the most recent period of diagnosis, enabled us to show higher
      survival rates for total cancer, childhood cancer, rectal cancer, melanoma,
      breast cancer, prostate cancer and acute leukaemia, but also lower rates for
      laryngeal and bladder cancer. Period analysis should be the preferred tool for
      showing up-to-date survival rates to cancer patients and their physicians.

PMID- 16418309
TI  - Do oncologists discuss expensive anti-cancer drugs with their patients?
AB  - BACKGROUND: In Australia, some anti-cancer drugs are only available at
      significant financial cost to patients. We sought the views and practices of
      Australian medical oncologists regarding discussion of high cost drugs (HCDs).
      PARTICIPANTS AND METHODS: A postal survey was mailed to all 274 members of the
      Medical Oncology Group of Australia. Three clinical scenarios described HCDs
      associated with either improved overall survival, encouraging response rate in a
      treatment-refractory cancer, or a scenario with improved treatment tolerability.
      Participants were asked about their discussion and prescription of HCDs. RESULTS:
      There was a 78% response rate. Most respondents were male (71%), worked in a
      metropolitan practice (87%) and spent more than 50% of their working time in
      patient care (87%). Forty-eight percent had previously prescribed a HCD. In the
      three scenarios, respondents would generally prescribe the drug if it were
      subsidised, however, between 28% and 41% (depending on the scenario) would not
      mention the HCD if it were not subsidised. Major reasons for not mentioning the
      HCD were concerns that discussion would 'worry the patient' or that the doctor
      would 'feel bad'. CONCLUSIONS: Despite literature suggesting that patients wish
      to be well informed and active participants in decision making, the practice of a
      significant percentage of Australian medical oncologists may prevent this.

PMID- 16418308
TI  - Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic
      cells (DC) in first-line treatment of patients with metastatic melanoma: a
      randomized phase III trial of the DC study group of the DeCOG.
AB  - BACKGROUND: This randomized phase III trial was designed to demonstrate the
      superiority of autologous peptide-loaded dendritic cell (DC) vaccination over
      standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. PATIENTS
      AND METHODS: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC
      vaccines loaded with MHC class I and II-restricted peptides were applied
      subcutaneously at 2-week intervals for the first five vaccinations and every 4
      weeks thereafter. The primary study end point was objective response (OR);
      secondary end points were toxicity, overall (OS) and progression-free survival
      (PFS). RESULTS: At the time of the first interim analysis 55 patients had been
      enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC:
      3.8%), but not significantly different in the two arms. The Data Safety &
      Monitoring Board recommended closure of the study. Unscheduled subset analyses
      revealed that patients with normal serum LDH and/or stage M1a/b survived longer
      in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC
      arm did those patients with (i) an initial unimpaired general health status
      (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44- haplotype survive significantly
      longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in
      the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated
      patients). CONCLUSIONS: DC vaccination could not be demonstrated to be more
      effective than DTIC chemotherapy in stage IV melanoma patients. The observed
      association of overall performance status and HLA haplotype with overall survival
      for patients treated by DC vaccination should be tested in future trials
      employing DC vaccines.

PMID- 16418310
TI  - Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal
      cell cancer: a review.
AB  - Advanced and metastatic renal cell cancer (RCC) is resistant to conventional
      chemotherapy. Only a very small number of patients survive long term after
      immunotherapy. However, any effect of interleukin-2 (IL-2) and/or interferon on
      median overall survival is small, and treatment-associated toxicities may be
      severe. The disease is therefore an area of high unmet medical need. Activation
      of the VEGF and EGF/RAS/RAF/MAP kinase pathways is frequent in solid tumours such
      as RCC. Such activation is implicated in tumour angiogenesis and proliferation.
      VEGF and EGF receptors and molecules (such as RAF kinase) involved in downstream
      signalling are therefore potential appropriate targets for drug therapy. Several
      antibodies and low molecular weight tyrosine kinase inhibitors (TKIs) have
      completed phase II clinical trials. Phase II studies of multitargeted agents,
      which include inhibition of VEGFR tyrosine kinase in their repertoire (sorafenib,
      sunitinib and AG 013736), show clear second-line activity in metastatic RCC. The
      same is true of the anti-VEGF antibody, bevacizumab. In a randomised phase III
      comparison against placebo in pretreated patients, sorafenib doubled median
      progression free survival (24 versus 12 weeks). Studies now in progress will
      determine whether benefits seen second-line will also be evident first-line, and
      whether the activity of novel agents can be increased by combining them with each
      other, with cytokines, or with chemotherapy.

PMID- 16418311
TI  - Performance of a decision rule to predict need for computed tomography among
      children with blunt head trauma.
AB  - OBJECTIVE: To assess the ability of the NEXUS II head trauma decision instrument
      to identify patients with clinically important intracranial injury (ICI) from
      among children with blunt head trauma. METHODS: An analysis was conducted of the
      pediatric cohort involved in the derivation set of National Emergency X
      Radiography Utilization Study II (NEXUS II), a prospective, observational,
      multicenter study of all patients who had blunt head trauma and underwent cranial
      computed tomography (CT) imaging at 1 of 21 emergency departments. We determined
      the test performance characteristics of the 8-variable NEXUS II decision
      instrument, derived from the entire NEXUS II cohort, in the pediatric cohort (0
      18 years of age), as well as in the very young children (<3 years). Clinically
      important ICI was defined as ICI that required neurosurgical intervention
      (craniotomy, intracranial pressure monitoring, or mechanical ventilation) or was
      likely to be associated with significant long-term neurologic impairment.
      RESULTS: NEXUS II enrolled 1666 children, 138 (8.3%) of whom had clinically
      important ICI. The decision instrument correctly identified 136 of the 138 cases
      and classified 230 as low risk. A total of 309 children were younger than 3
      years, among whom 25 had ICI. The decision instrument identified all 25 cases of
      clinically important ICI in this subgroup. CONCLUSIONS: The decision instrument
      derived in the large NEXUS II cohort performed with similarly high sensitivity
      among the subgroup of children who were included in this study. Clinically
      important ICI were rare in children who did not exhibit at least 1 of the NEXUS
      II risk criteria.

PMID- 16418312
TI  - Ventricular septal defect with secondary left ventricular-to-right atrial shunt
      is associated with a higher risk for infective endocarditis and a lower late
      chance of closure.
AB  - OBJECTIVE: Although ventricular septal aneurysm may diminish or even close the
      shunt through the ventricular septal defect (VSD), developing a left ventricular
      to-right atrial (LV-RA) shunt may be unfavorable. This study sought to clarify
      this issue on the basis of an extended observation of such patients. METHODS:
      Sixty-eight patients (1201 patient-years) who had small perimembranous VSD and LV
      RA shunt and were not operated on before 6 years of age were studied. RESULTS:
      The onset age of LV-RA shunt was 5.8 +/- 3.3 years, with clinical improvement
      later observed in 23 (34%). The murmur disappeared and showed spontaneous closure
      in 5 (7%). Seven episodes of infective endocarditis occurred in 6 (8.7%, or 58
      per 10000 patient-years), with 2 receiving surgery. Another 4 received surgery
      during follow-up. With echocardiography, aneurysmal transformation involving the
      anterior and septal leaflets of tricuspid valve (double sac) was found in 56
      (85%), whereas only the septal leaflet (single sac) was involved in 10. Patients
      with double sac were less likely to show improvement, whereas patients who had
      superior QRS axis and were female showed clinical improvement more frequently.
      CONCLUSIONS: VSD with secondary LV-RA shunt is associated with a higher risk for
      infective endocarditis but still has a low chance for late improvement and even
      closure.

PMID- 16418313
TI  - Birth weight and cardiac structure in children.
AB  - OBJECTIVE: Epidemiologic studies have shown associations between impaired fetal
      growth and risk for coronary heart disease in adults. The underlying mechanisms
      are unknown. We investigated whether restricted intrauterine growth affects
      cardiac structure. METHODS: We performed echocardiography on 216 9-year-old
      children who were measured previously at birth. The diameter of the coronary left
      and right main branches was derived from the widest dimension; total coronary
      artery diameter was calculated by adding the diameters of the left and right
      coronary arteries. Aortic root diameter, left atrial diameter, left ventricular
      diameter, left ventricular outflow tract diameter, and left ventricular mass were
      measured. RESULTS: On average, children who had weighed less at birth had a
      smaller total coronary artery diameter, aortic root diameter, and left
      ventricular outflow tract diameter after adjustment for gender, gestational age,
      current height and weight, and maternal height and prepregnant weight. For each
      SD increase in birth weight, total coronary diameter rose by 0.10 mm, log aortic
      root diameter rose by 1.5%, and log left ventricular outflow tract diameter rose
      by 1.6%. CONCLUSION: Impaired fetal growth may have long-term effects on cardiac
      structure. This may help to explain why adults whose birth weight was low are at
      greater risk for coronary heart disease.

PMID- 16418314
TI  - Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM): A
      novel method for biomolecular screening.
AB  - Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) is a
      new separation-based affinity method. It has kinetic capabilities exceeding those
      of surface plasmon resonance (SPR) and does not require immobilization of
      molecules on the surface. Another distinctive feature of NECEEM is that--if it is
      combined with an advanced method for the mixing solutions inside a capillary,
      termed transverse diffusion of laminar flow profiles (TDLFP)--it requires only
      nanoliter volumes of solutions. The proven applications of NECEEM to biomolecular
      screening include 1) measuring kinetic and thermodynamic parameters of protein
      ligand interactions, 2) quantitative affinity analyses of proteins and
      hybridization analyses of DNA and RNA, and 3) selection of binding ligands from
      combinatorial libraries. NECEEM is easy to automate and parallelize. Because of
      its simplicity and analytical power, NECEEM has the potential to become a
      workhorse in studies of biomolecular interactions. The author reviews theoretical
      bases of NECEEM and its applications to biomolecular screening.

PMID- 16418315
TI  - Support vector machines in HTS data mining: Type I MetAPs inhibition study.
AB  - This article reports a successful application of support vector machines (SVMs)
      in mining high-throughput screening (HTS) data of a type I methionine
      aminopeptidases (MetAPs) inhibition study. A library with 43,736 small organic
      molecules was used in the study, and 1355 compounds in the library with 40% or
      higher inhibition activity were considered as active. The data set was randomly
      split into a training set and a test set (3:1 ratio). The authors were able to
      rank compounds in the test set using their decision values predicted by SVM
      models that were built on the training set. They defined a novel score PT50, the
      percentage of the test set needed to be screened to recover 50% of the actives,
      to measure the performance of the models. With carefully selected parameters, SVM
      models increased the hit rates significantly, and 50% of the active compounds
      could be recovered by screening just 7% of the test set. The authors found that
      the size of the training set played a significant role in the performance of the
      models. A training set with 10,000 member compounds is likely the minimum size
      required to build a model with reasonable predictive power.

PMID- 16418316
TI  - Biosensor-based screening and characterization of HIV-1 inhibitor interactions
      with Sap 1, Sap 2, and Sap 3 from Candida albicans.
AB  - A surface plasmon resonance (SPR) biosensor-based strategy for identification and
      characterization of compounds has been devised as a tool for the discovery of
      specific drugs for treatment of Candida albicans infections. Three secreted
      aspartic proteases (Saps 1-3) from C. albicans were used as parallel targets. The
      stepwise procedure involved screening of 104 HIV-1 pro-tease inhibitors at a
      single concentration for binding to the targets. Twenty-four compounds that
      appeared to interact with the targets were identified in the screen. False
      positives and compounds with low affinities or very fast dissociation rates could
      be removed after a series of additional measurements of these compounds at 3
      different concentrations. Kinetic characterization was performed with 13
      compounds, giving information about the interaction mechanism and interaction
      kinetic parameters (k(on), k(off), and K(D)). The pH dependence of the
      interaction and the inhibitory effect of a final small set of compounds were also
      evaluated. The strategy resulted in the identification of ritonavir as the
      compound generally exhibiting the highest affinity for the Candida enzymes. It
      had similar interaction kinetic characteristics for Sap 1 and Sap 2 but a lower
      affinity for Sap 3 due to a slower association rate. Several additional compounds
      with high affinity and/or slow dissociation rates for the targets were
      identified, revealing 2 other structural scaffolds for Sap inhibitors. In
      addition, important differences in the specificity for these types of compounds
      by the Saps were identified. The stepwise biosensor-based strategy was
      consequently efficient for identification and characterization of new lead
      compounds for 3 important drug targets.

PMID- 16418317
TI  - Reporter gene recombination in juxtaglomerular granular and collecting duct cells
      by human renin promoter-Cre recombinase transgene.
AB  - To assess the feasibility of using the renin promoter for expressing Cre
      recombinase in juxtaglomerular (JG) cells only, we generated five independent
      transgenic mouse lines (designated hRen-Cre) expressing Cre recombinase under
      control of a 12.2-kb human renin promoter. In the kidneys of adult mice Cre mRNA
      (RT-PCR) was found in the renal cortex, with Cre protein (immunohistochemistry)
      being localized in afferent arterioles and to a lower degree in interlobular
      arteries. Cre mRNA levels were regulated in a renin-typical fashion by changes in
      oral salt intake, water restriction, or isoproterenol infusion, indicating the
      presence of key regulatory elements within 12.2 kb of the 5'-flanking region of
      the human renin gene. hRen-Cre mice were interbred with both the ROSA26-EGFP and
      ROSA26-lacZ reporter strains to assess renin promoter activity from Cre-mediated
      excision of a floxed stop cassette and subsequent enhanced green fluorescent
      protein (EGFP) and beta-galactosidase (beta-gal) detection. In adult mice, beta
      gal staining and EGFP were observed in afferent arterioles and interlobular
      arteries, overlapping with Cre protein expression. In addition, intense beta-gal
      staining was found in cortical and medullary collecting ducts where Cre
      expression was minimal. In embryonic kidneys, beta-gal staining was detected in
      the developing collecting duct system beginning at embryonic day 12, showing
      substantial activity of the human renin promoter in the branching ureteric bud.
      Our data indicate that besides its well-known activity in JG cells and renal
      vessels the human renin promoter is transiently active in the collecting duct
      system during kidney development, complicating the use of this approach for JG
      cell-specific excision of floxed targets.

PMID- 16418318
TI  - Inhibition of LINE-1 expression in the heart decreases ischemic damage by
      activation of Akt/PKB signaling.
AB  - Microarray analyses indicate that ischemic and pharmacological preconditioning
      suppress overexpression of the non-long terminal repeat retrotransposon long
      interspersed nuclear element 1 (LINE-1, L1) after ischemia-reperfusion in the rat
      heart. We tested whether L1 overexpression is mechanistically involved in
      postischemic myocardial damage. Isolated, perfused rat hearts were treated with
      antisense or scrambled oligonucleotides (ODNs) against L1 for 60 min and exposed
      to 40 min of ischemia followed by 60 min of reperfusion. Functional recovery and
      infarct size were measured. Effective nuclear uptake was determined by FITC
      labeled ODNs, and downregulation of L1 transcription was confirmed by RT-PCR.
      Immunoblot analysis was used to assess changes in expression levels of the L1
      encoded proteins ORF1p and ORF2p. Immunohistochemistry was performed to localize
      ORF1/2 proteins in cardiac tissue. Effects of ODNs on prosurvival protein kinase
      B (Akt/PKB) expression and activity were also determined. Antisense ODNs against
      L1 prevented L1 burst after ischemia-reperfusion. Inhibition of L1 increased
      Akt/PKBbeta expression, enhanced phosphorylation of PKB at serine 473, and
      markedly improved postischemic functional recovery and decreased infarct size.
      Antisense ODN-mediated protection was abolished by LY-294002, confirming the
      involvement of the Akt/PKB survival pathway. ORF1p and ORF2p were found to be
      expressed in rat heart. ORF1p showed a predominantly nuclear localization in
      cardiomyocytes, whereas ORF2p was exclusively present in endothelial cells. ORF1p
      levels increased in response to ischemia, which was reversed by antisense ODN
      treatment. No significant changes in ORF2p were noted. Our results demonstrate
      that L1 suppression favorably affects postischemic outcome in the heart.
      Modifying transcriptional activity of L1 may represent a novel anti-ischemic
      therapeutic strategy.

PMID- 16418319
TI  - Proteomic profiles of serum inflammatory markers accurately predict
      atherosclerosis in mice.
AB  - At a population level, inflammatory markers have been shown to predict outcome
      and response to therapy in patients with atherosclerotic cardiovascular disease.
      However, current markers are not sufficiently sensitive or specific to provide
      clinical utility for managing individual patients. We hypothesize that
      measurement of multiple circulating disease-related inflammatory factors will be
      more informative, allowing the early identification of vascular wall disease
      activity. We have investigated whether protein microarray-based abundance
      measurements of circulating proteins can predict the severity of atherosclerotic
      disease. Using a longitudinal experimental design with apolipoprotein E-deficient
      mice and control C57Bl/6J and C3H/HeJ wild-type mice, we measured the time
      related serum protein expression of 30 inflammatory markers using a protein
      microarray. We were able to identify a subset of proteins that classify and
      predict the severity of atherosclerotic disease with a high level of accuracy.
      The time-specific vascular expression of these markers was verified by showing
      that their gene expression in the mouse aorta correlated closely to the temporal
      pattern of serum protein levels. In conclusion, these data suggest that
      quantification of multiple disease-related inflammatory proteins can provide a
      more sensitive and specific methodology for assessing atherosclerotic disease
      activity in humans, and identify candidate biomarkers for such studies.

PMID- 16418321
TI  - Distinct pattern of lung gene expression in the Cftr-KO mice developing
      spontaneous lung disease compared with their littermate controls.
AB  - Cystic fibrosis (CF) is caused by a defect in the CF transmembrane conductance
      regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the
      CFTR protein results in salty sweat, pancreatic insufficiency, intestinal
      obstruction, male infertility, and severe pulmonary disease. Most of the
      morbidity and mortality of CF patients results from pulmonary complications.
      Differences in susceptibility to bacterial infection and variable degree of CF
      lung disease among CF patients remain unexplained. Many phenotypic expressions of
      the disease do not directly correlate with the type of mutation in the Cftr gene.
      Using a unique CF mouse model that mimics aspects of human CF lung disease, we
      analyzed the differential gene expression pattern between the normal lungs of
      wild-type mice (WT) and the affected lungs of CFTR knockout mice (KO). Using
      microarray analysis followed by quantitation of candidate gene mRNA and protein
      expression, we identified many interesting genes involved in the development of
      CF lung disease in mice. These findings point to distinct mechanisms of gene
      expression regulation between mice with CF and control mice.

PMID- 16418320
TI  - Gene expression in ductus arteriosus and aorta: comparison of birth and oxygen
      effects.
AB  - Ductus arteriosus (DA) closure is initiated by oxygen rise postnatally and
      progresses in two, functional-to-permanent, stages. Here, using GeneChip Arrays
      in rats (normoxic and hyperoxic fetus, normoxic newborn), we examined whether
      oxygen alone duplicates the birth process in affecting DA genes. In addition, by
      comparing DA with aorta (Ao), we identified features in postnatal gene profile
      marking transitional adjustments in a closing (DA) vs. a persistent (Ao) vessel.
      We found changes in neonatal DA denoting enhanced formation and action of the
      constrictor endothelin-1 (ET-1). Likewise, ANG II type 1 receptor was
      upregulated, and the compound was a constrictor. Conversely, relaxant PGE2 became
      less effective. Among agents for functional closure, only ET-1 was affected
      similarly by oxygen and birth. Coincidentally, neonatal DA showed enhanced
      contractile drive with upregulation of Rho-Rho kinase and calcium signaling along
      with downregulation of contractile proteins. The latter effect was shared by
      oxygen. Changes denoting active remodeling were also seen in neonatal but not
      hyperoxic fetal DA. Ao, unlike DA, exhibited postnatal variations in
      noradrenergic, purinergic, and PGI2 systems with opposing effects on vasomotion.
      Contraction and remodeling processes were also less affected by birth, whereas
      lipid and glucose metabolism were upregulated. We conclude that several agents,
      including ANG II as novel effector, promote functional closure of DA, but only ET
      1 is causally coupled with oxygen. Oxygen has no role in processes for permanent
      closure. Functional closure is associated with downregulation of contractile
      apparatus, and this may render neonatal DA less amenable to tone manipulation.
      Conceivably, activation of metabolism in neonatal Ao is a distinguishing feature
      for transitional adaptations in the permanent vasculature.

PMID- 16418322
TI  - Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, adverse
      effects, and drug interactions of lapatinib. DATA SOURCES: A PubMed search was
      conducted (1966-August 2005) using the following terms: lapatinib, GW572016, and
      dual tyrosine kinase inhibitor. Additional information sources included meeting
      abstracts, clinical trial data, and bibliographies from articles identified
      through PubMed. STUDY SELECTION AND DATA EXTRACTION: Preclinical and clinical
      trials that evaluated lapatinib in cell culture, animal models, and human
      subjects were selected from the data sources. Pivotal in vitro data and all in
      vivo data published regarding lapatinib were included. DATA SYNTHESIS: The
      development of tyrosine kinase inhibitors has resulted from a search for targeted
      cancer therapeutics made possible by recent gains in our understanding of tumor
      cell biology. Lapatinib is a dual tyrosine kinase inhibitor selective for
      inhibition of epidermal growth factor receptor and human epidermal growth factor
      receptor-2 autophosphorylation, leading to suppression of proliferation pathways
      of solid tumors. Lapatinib has shown clinical activity in solid tumors, with the
      most notable in advanced or metastatic breast cancer, including tumors refractory
      to trastuzumab. It has a mild adverse effect profile, with the most common
      adverse events being diarrhea and rash. CONCLUSIONS: Lapatinib has novel, dual
      tyrosine kinase inhibitory properties selective for factors overexpressed in some
      solid tumors. Results from preclinical and Phase I/II trials indicate activity in
      the treatment of solid tumors, especially advanced or metastatic breast cancer.
      Application for approval is anticipated pending results of ongoing Phase III
      trials.

PMID- 16418323
TI  - Hepatitis associated with low-dose venlafaxine for postmenopausal vasomotor
      symptoms.
AB  - OBJECTIVE: To report a case of drug-induced hepatitis associated with low-dose
      venlafaxine. CASE SUMMARY: A 60-year-old white woman receiving venlafaxine 75 mg
      daily for vasomotor symptoms presented after one month of therapy with
      nonspecific complaints, including abdominal pain. A series of diagnostic and
      laboratory tests revealed an enlarged liver and elevated alanine aminotransferase
      (ALT) up to 372 U/L, aspartate aminotransferase (AST) up to 99 U/L, gamma
      glutamyltransferase (GGT) up to 962 U/L, and alkaline phosphatase up to 758 U/L.
      All potential hepatotoxic medications were discontinued. Within one week after
      stopping venlafaxine, her liver function test results showed marked improvement.
      Almost 4 weeks after discontinuing therapy, venlafaxine 37.5 mg was reinitiated.
      Her ALT, AST, GGT, and alkaline phosphatase again increased to 269, 49, 256, and
      263 U/L, respectively, 6 days after resuming therapy. Upon discontinuation of
      venlafaxine, her liver function abnormalities resolved. DISCUSSION: This case is
      significant due to the severity of symptoms and consequent liver function test
      results involved in diagnosing drug-induced hepatitis. It is also remarkable
      because of the hepatotoxicity that occurred initially and on rechallenge with low
      dose venlafaxine. The hepatotoxic effects of venlafaxine have been characterized
      as rare and idiosyncratic. The Naranjo probability scale revealed that the
      adverse drug event was probable. CONCLUSIONS: Venlafaxine therapy can lead to
      drug-induced hepatitis, even when used at low doses. Clinicians should be aware
      of this possible adverse effect of venlafaxine therapy and monitor patients
      closely after initiation of therapy.

PMID- 16418324
TI  - Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits
      proliferation and promotes differentiation of BCR/ABL-expressing cells.
AB  - Translational regulation by oncogenic proteins may be a rapid and efficient
      mechanism to modulate gene expression. We report here the identification of the
      CEBPB gene as a target of translational regulation in myeloid precursor cells
      transformed by the BCR/ABL oncogene. Expression of CEBPB was repressed in 32D
      BCR/ABL cells and reinduced by imatinib (STI571) via a mechanism that appears to
      depend on expression of the CUG-repeat RNA-binding protein CUGBP1 and the
      integrity of the CUG-rich intercistronic region of c/ebpbeta mRNA. Constitutive
      expression or conditional activation of wild-type CEBPB induced differentiation
      and inhibited proliferation of 32D-BCR/ABL cells in vitro and in mice, but a DNA
      binding-deficient CEBPB mutant had no effect. The proliferation-inhibitory effect
      of CEBPB was, in part, mediated by the CEBPB-induced GADD45A gene. Because
      expression of CEBPB (and CEBPA) is low in the blast crisis (BC) stage of chronic
      myelogenous leukemia (CML) and is inversely correlated with BCR/ABL tyrosine
      kinase levels, these findings point to the therapeutic potential of restoring
      C/EBP activity in CML-BC and, perhaps, other types of acute leukemia.

PMID- 16418325
TI  - The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine
      hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like
      disease.
AB  - Dysregulated tyrosine kinase activity by the Fip1-like1 (FIP1L1)-platelet-derived
      growth factor receptor alpha (PDGFRA) (F/P) fusion gene has been identified as a
      cause of clonal hypereosinophilic syndrome (HES), called F/P-positive chronic
      eosinophilic leukemia (CEL) in humans. However, transplantation of F/P-transduced
      hematopoietic stem cells/progenitors (F/P(+) HSCs/Ps) into mice results in a
      chronic myelogenous leukemia-like disease, which does not resemble HES. Because a
      subgroup of patients with HES show T-cell-dependent interleukin-5 (IL-5)
      overexpression, we determined if expression of the F/P fusion gene in the
      presence of transgenic T-cell IL-5 overexpression in mice induces HES-like
      disease. Mice that received a transplant of CD2-IL-5-transgenic F/P(+) HSC/Ps (IL
      5Tg-F/P) developed intense leukocytosis, strikingly high eosinophilia, and
      eosinophilic infiltration of nonhematopoietic as well as hematopoietic tissues, a
      phenotype resembling human HES. The disease phenotype was transferable to
      secondary transplant recipients of a high cell dose, suggesting involvement of a
      short-term repopulating stem cell or an early myeloid progenitor. Induction of
      significant eosinophilia was specific for F/P since expression of another fusion
      oncogene, p210-BCR/ABL, in the presence of IL-5 overexpression was characterized
      by a significantly lower eosinophilia than IL-5Tg-F/P recipients. These results
      suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires
      a second event associated with IL-5 overexpression.

PMID- 16418326
TI  - Activated CD4+CD25+ T cells selectively kill B lymphocytes.
AB  - The suppressive capacity of naturally occurring mouse CD4+CD25+ T cells on T-cell
      activation has been well documented. The present study is focused on the
      interaction of CD4+CD25+ T cells and B cells. By coculturing preactivated
      CD4+CD25+ T cells with B cells in the presence of polyclonal B-cell activators,
      we found that B-cell proliferation was significantly suppressed. The suppression
      of B-cell proliferation was due to increased cell death caused by the CD4+CD25+ T
      cells in a cell-contact-dependent manner. The induction of B-cell death is not
      mediated by Fas-Fas ligand pathway, but surprisingly, depends on the up
      regulation of perforin and granzymes in the CD4+CD25+ T cells. Furthermore,
      activated CD4+CD25+ T cells preferentially killed antigen-presenting but not
      bystander B cells. Our results demonstrate that CD4+CD25+ T cells can act
      directly on B cells and suggest that the prevention of autoimmunity by CD4+CD25+
      T cells can be explained, at least in part, by the direct regulation of B-cell
      function.

PMID- 16418328
TI  - Significance of circulating T-cell clones in Sezary syndrome.
AB  - Identification of malignant Sezary cells by T-cell receptor (TCR) clonality
      studies is routinely used for the diagnosis of Sezary syndrome, but T-cell clones
      expressed in a single patient have never been accurately characterized. We
      previously reported that CD158k expression delineates Sezary syndrome malignant
      cells, and, more recently, we identified vimentin at the surface membranes of
      Sezary cells and normal activated lymphocytes. In the present study, T-cell
      clones from 13 patients with Sezary syndrome were identified by immunoscopy and
      further characterized in the blood according to their TCR Vbeta, CD158k, and
      vimentin cell-surface expression. We found in most patients a unique malignant T
      cell clone that coexpressed CD158k and vimentin and that, when patients were
      tested, was also present in the skin. However, in some patients we detected the
      presence of a nonmalignant circulating clone expressing high amounts of vimentin
      and lacking CD158k. These results indicate that clonal expansion may originate
      from circulating malignant and nonmalignant CD4(+) T cell populations in patients
      with Sezary syndrome. Identification of the malignant cells in Sezary syndrome
      cannot be achieved by T-cell clonality studies or by TCR Vbeta monoclonal
      antibody (mAb) analysis alone; it also relies on CD158k phenotyping.

PMID- 16418327
TI  - Vasoactive intestinal peptide induces regulatory dendritic cells that prevent
      acute graft-versus-host disease while maintaining the graft-versus-tumor
      response.
AB  - Acute graft-versus-host disease (GVHD) is a major cause of morbidity and
      mortality in patients undergoing allogeneic bone marrow transplantation (BMT) for
      the treatment of leukemia and other immunogenetic disorders. The use of
      tolerogenic dendritic cells (DCs) that induce the generation/activation of
      regulatory T (Tr) cells for the treatment of acute GVHD following allogeneic BMT
      has been recently established. Therefore, the identification of factors that
      contribute to the development of tolerogenic DCs is highly relevant. We report on
      the use of the known immunosuppressive neuropeptide, the vasoactive intestinal
      peptide (VIP), as a new approach to induce tolerogenic DCs with the capacity to
      prevent acute GVHD. DCs differentiated in the presence of VIP impair allogeneic
      haplotype-specific responses of donor CD4(+) cells in mice given transplants by
      inducing the generation of Tr cells in the graft. VIP-induced tolerogenic DCs did
      not abrogate the graft-versus-leukemia response presumably by not affecting the
      cytotoxicity of transplanted T cells against the leukemic cells. Therefore, the
      inclusion of VIP-induced tolerogenic DCs in future therapeutic regimens may
      minimize the dependence on nonspecific immunosuppressive drugs used currently as
      antirejection therapy, and facilitate the successful transplantation from
      mismatched donors, by reducing the deleterious consequences of acute GVHD and
      extending the applicability of BMT.

PMID- 16418329
TI  - Shedding of lymphocyte function-associated antigen-1 (LFA-1) in a human
      inflammatory response.
AB  - Shedding of adhesion molecules has been described for members of the selectin and
      immunoglobulin superfamilies, but integrins are not known to be shed. Here, we
      describe shedding of the integrin lymphocyte function-associated antigen-1 (LFA
      1; CD11a/CD18) from human leukocytes during the cutaneous inflammatory response
      to the blistering agent cantharidin. Expression of LFA-1 was significantly
      diminished on blister-infiltrated neutrophils (P < .001) and monocytes (P = .02)
      compared with cells in peripheral blood, but expression on lymphocytes remained
      unchanged. A capture enzyme-linked immunosorbent assay (ELISA) indicated that LFA
      1 was shed into blister fluid as a heterodimer expressing an intact headpiece
      with I and I-like epitopes. However, a CD11a central region epitope, G25.2, was
      absent and this remained expressed as a "stub" on the cell surface of blister
      neutrophils. Western analysis of soluble LFA-1 revealed a truncated 110-kDa CD11a
      chain and a minimally truncated 86-kDa CD18 chain. However, LFA-1 was shed in a
      ligand-binding conformation, since it expressed KIM-127 and 24 activation
      epitopes and bound to solid-phase ICAM-1. Shed LFA-1 was also detected in a
      synovial effusion by ELISA and Western analysis. We hypothesize that LFA-1
      shedding may play a role in leukocyte detachment after transendothelial migration
      and in regulating integrin-dependent outside-in signaling.

PMID- 16418330
TI  - P-selectin binds to the D'-D3 domains of von Willebrand factor in Weibel-Palade
      bodies.
AB  - It has recently been shown that the ultralarge platelet-recruiting von Willebrand
      factor (VWF) strings formed immediately at exocytosis from endothelial cells may
      be anchored to the cell surface by interaction with the integral membrane protein
      P-selectin. This finding of a new binding partner for VWF immediately prompts the
      question which domains of VWF bind to P-selectin. We have exploited the fact that
      VWF expression in HEK293 cells triggers the formation of Weibel-Palade body-like
      structures that can recruit P-selectin. A suitably modified version of this assay
      using coexpressed truncations of VWF, together with P-selectin variants in HEK293
      cells, allowed us to determine which domains of VWF would recruit P-selectin
      within a physiologically appropriate intracellular environment. Confirming the
      results of such a cellular assay by conventional coimmunoprecipitation, we
      concluded that the lumenal domain of P-selectin interacts with the D'-D3 domains
      of VWF.

PMID- 16418331
TI  - Endothelial-cell apoptosis induced by cleaved high-molecular-weight kininogen
      (HKa) is matrix dependent and requires the generation of reactive oxygen species.
AB  - High-molecular-weight kininogen (HK) is an abundant plasma protein that plays a
      central role in activation of the kallikrein-kinin system. Cleavage of HK by
      plasma kallikrein results in release of the nonapeptide bradykinin (BK), leaving
      behind cleaved high-molecular-weight kininogen (HKa). Previous studies have
      demonstrated that HKa induces apoptosis of proliferating endothelial cells and
      inhibits angiogenesis in vivo, activities mediated primarily through its domain
      5. However, the mechanisms by which these effects occur are not well understood.
      Here, we demonstrate that HKa induces apoptosis of endothelial cells cultured on
      gelatin, vitronectin, fibronectin, or laminin but not collagen type I or IV. The
      ability of HKa to induce endothelial-cell apoptosis is dependent on the
      generation of intracellular reactive oxygen species and associated with depletion
      of glutathione and peroxidation of endothelial-cell lipids, effects that occur
      only in cells cultured on matrix proteins permissive for HKa-induced apoptosis.
      Finally, the ability of HKa to induce endothelial-cell apoptosis is blocked by
      the addition of reduced glutathione or N-acetylcysteine. These studies
      demonstrate a unique role for oxidant stress in mediating the activity of an
      antiangiogenic polypeptide and highlight the importance of the extracellular
      matrix in regulating endothelial-cell survival.

PMID- 16418333
TI  - High levels of circulating CD34 cells, dacrocytes, clonal hematopoiesis, and JAK2
      mutation differentiate myelofibrosis with myeloid metaplasia from secondary
      myelofibrosis associated with pulmonary hypertension.
AB  - We studied 25 patients with myelofibrosis with myeloid metaplasia and 19 patients
      with secondary myelofibrosis associated with pulmonary hypertension (PH). In
      these 2 groups, we compared the peripheral-blood CD34 count, the clonality of
      granulocytes and platelets in peripheral blood, the mutational status of the JAK2
      kinase gene, and the morphology of the peripheral blood and bone marrow. We found
      that the following were distinctive features of myelofibrosis with myeloid
      metaplasia but not of secondary myelofibrosis due to PH: high circulating CD34
      cell count, the presence of clonal platelets and granulocytes and of peripheral
      blood dacrocytes, and a JAK2 1849G>T (V617F) mutation. We conclude that these are
      intrinsic features of clonal progenitors present in patients with myelofibrosis
      due to myeloproliferative disorders and that these features are not due to the
      abnormal marrow architecture seen in secondary myelofibrosis.

PMID- 16418332
TI  - Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces
      in vitro and in vivo cytotoxicity in human multiple myeloma cells.
AB  - Perifosine is a synthetic novel alkylphospholipid, a new class of antitumor
      agents which targets cell membranes and inhibits Akt activation. Here we show
      that baseline phosphorylation of Akt in multiple myeloma (MM) cells is completely
      inhibited by perifosine [octadecyl-(1,1-dimethyl-piperidinio-4-yl)-phosphate] in
      a time- and dose-dependent fashion, without inhibiting phosphoinositide-dependent
      protein kinase 1 phosphorylation. Perifosine induces significant cytotoxicity in
      both MM cell lines and patient MM cells resistant to conventional therapeutic
      agents. Perifosine does not induce cytotoxicity in peripheral blood mononuclear
      cells. Neither exogenous interleukin-6 (IL-6) nor insulinlike growth factor 1
      (IGF-1) overcomes Perifosine-induced cytotoxicity. Importantly, Perifosine
      induces apoptosis even of MM cells adherent to bone marrow stromal cells.
      Perifosine triggers c-Jun N-terminal kinase (JNK) activation, followed by caspase
      8/9 and poly (ADP)-ribose polymerase cleavage. Inhibition of JNK abrogates
      perifosine-induced cytotoxicity, suggesting that JNK plays an essential role in
      perifosine-induced apoptosis. Interestingly, phosphorylation of extracellular
      signal-related kinase (ERK) is increased by perifosine; conversely, MEK inhibitor
      synergistically enhances Perifosine-induced cytotoxicity in MM cells.
      Furthermore, perifosine augments dexamethasone, doxorubicin, melphalan, and
      bortezomib-induced MM cell cytotoxicity. Finally, perifosine demonstrates
      significant antitumor activity in a human plasmacytoma mouse model, associated
      with down-regulation of Akt phosphorylation in tumor cells. Taken together, our
      data provide the rationale for clinical trials of perifosine to improve patient
      outcome in MM.

PMID- 16418335
TI  - Preferential inhibition of the magnesium-dependent strand transfer reaction of
      HIV-1 integrase by alpha-hydroxytropolones.
AB  - Integration is a crucial step in the life cycle of human immunodeficiency virus
      type 1 (HIV-1); therefore, inhibitors of HIV-1 integrase are candidates for
      antiretroviral therapy. Two 7-hydroxytropolone derivatives (alpha
      hydroxytropolones) were found to inhibit HIV-1 integrase. A structure-activity
      relationship investigation with several tropolone derivatives from The National
      Cancer Institute compound repository demonstrated that the 7-hydroxy group is
      essential for integrase inhibition. alpha-Hydroxytropolones preferentially
      inhibit strand transfer and are inhibitory both in the presence of magnesium or
      manganese. Lack of inhibition of disintegration in the presence of magnesium
      coupled with results from different cross-linking assays suggests alpha
      hydroxytropolones as interfacial inhibitors. We propose that alpha
      hydroxytropolones chelate the divalent metal (Mg2+ or Mn2+) in the enzyme active
      site. The most active compound against HIV-1 integrase in biochemical assays
      [2,4,6-cycloheptatrien-1-one, 2,7-dihydroxy-4-isopropyl (NSC 18806) IC50 = 4.8 +/
      2.5 microM] exhibits weak cytoprotective activity against HIV-1(IIIB) in a cell
      based assay. alpha-Hydroxytropolones represent a new family of inhibitors for the
      development of novel drugs against HIV infection.

PMID- 16418336
TI  - The G12 family of G proteins as a reporter of thromboxane A2 receptor activity.
AB  - Despite advances in the understanding of pathways regulated by the G12 family of
      heterotrimeric G proteins, much regarding the engagement of this family by
      receptors remains unclear. We explore here, using the thromboxane A2 receptor
      TPalpha, the ability of G12 and G13 to report differences in the potency and
      efficacy of receptor ligands. We were interested especially in the potential of
      the isoprostane 8-iso-prostaglandin F (8-iso-PGF2alpha), among other ligands
      examined, to activate G12 and G13 through TPalpha explicitly. We were also
      interested in the functionality of TPalpha-Galpha fusion proteins germane to G12
      and G13. Using fusion proteins in Spodoptera frugiperda (Sf9) cells and
      independently expressed proteins in human embryonic kidney 293 cells, and using
      guanosine 5'-O-(3-[35S]thio)triphosphate binding to evaluate Galpha activation
      directly, we found for Galpha that no ligand tested, including 8-iso
      prostaglandin F (8-iso-PGF2alpha and a purported antagonist (pinane thromboxane
      A2), was silent. The activity of agonists was especially pronounced when
      evaluated for TPalpha-Galpha13 and in the context of receptor reserve. Agonist
      activity for 8-iso-PGF2 was diminished and that for pinane thromboxane A
      nonexistent when Galpha12 was the reporter. These data establish that G12 and G13
      can report differentially potency and efficacy and underscore the relevance of
      receptor and G protein context.

PMID- 16418334
TI  - Gene expression and angiotropism in primary CNS lymphoma.
AB  - Primary CNS lymphoma is an aggressive form of non-Hodgkin lymphoma whose growth
      is restricted to the central nervous system. We used cDNA microarray analysis to
      compare the gene expression signature of primary CNS lymphomas with nodal large B
      cell lymphomas. Here, we show that while individual cases of primary CNS
      lymphomas may be classified as germinal center B-cell, activated B-cell, or type
      3 large B-cell lymphoma, brain lymphomas are distinguished from nodal large B
      cell lymphomas by high expression of regulators of the unfolded protein response
      (UPR) signaling pathway, by the oncogenes c-Myc and Pim-1, and by distinct
      regulators of apoptosis. We demonstrate that interleukin-4 (IL-4) is expressed by
      tumor vasculature as well as by tumor cells in CNS lymphomas. We also identify
      high expression in CNS lymphomas of several IL-4-induced genes, including X-box
      binding protein 1 (XBP-1), a regulator of the UPR. In addition, we demonstrate
      expression of the activated form of STAT6, a mediator of IL-4 signaling, by tumor
      cells and tumor endothelia in CNS lymphomas. High expression of activated STAT6
      in tumors was associated with short survival in an independent set of patients
      with primary CNS lymphoma who were treated with high-dose intravenous
      methotrexate therapy.

PMID- 16418337
TI  - Antimony-based antileishmanial compounds prolong the cardiac action potential by
      an increase in cardiac calcium currents.
AB  - Antimonial agents are a mainstay for the treatment of leishmaniasis, a group of
      protozoal diseases that includes visceral leishmaniasis, or Kala Azar.
      Chemotherapy with trivalent potassium antimony tartrate (PAT) and, more
      importantly, pentavalent antimony-carbohydrate complexes, such as sodium
      stibogluconate (SSG), has been reported to prolong the QT interval and produce
      life-threatening arrhythmias. PAT is chemically related to As2O3, which alters
      cardiac excitability by inhibition of human ether a-go-go related gene (hERG)
      trafficking and an increase of cardiac calcium currents. In this study, we report
      that PAT does not block hERG currents on short-term exposure but reduces current
      density on long-term exposure (IC50, 11.8 microM) and inhibits hERG maturation on
      Western blots (IC50, 62 microM). Therapeutic concentrations of 0.3 microM PAT
      increase cardiac calcium currents from -4.8 +/- 0.7 to -7.3 +/- 0.5 pA/pF at 10
      mV. In marked contrast, pentavalent SSG, the drug of choice for the treatment of
      leishmaniasis, did not affect hERG/IKr or any other cardiac potassium current at
      therapeutic concentrations. However, both cardiac sodium and calcium currents
      were significantly increased on long-term exposure to 30 microM SSG in isolated
      guinea pig ventricular myocytes. We propose that the increase in calcium currents
      from -3.2 +/- 0.3 to -5.1 +/- 0.3 pA/pF at 10 mV prolongs APD90 from 464 +/- 35
      to 892 +/- 64 ms. Our data suggest that conversion of Sb(V) into active Sb(III)
      in patients produces a common mode of action for antimonial drugs, which define a
      novel compound class that increases cardiac risk not by a reduction of hERG/IKr
      currents but-for the first time-by an increase in cardiac calcium currents.

PMID- 16418338
TI  - Kinetics of penetration influence the apparent potency of vanilloids on TRPV1.
AB  - Evidence that the ligand binding site of TRPV1 lies on the inner face of the
      plasma membrane and that much of the TRPV1 itself is localized to internal
      membranes suggests that the rate of ligand entry into the cell may be an
      important determinant of the kinetics of ligand action. In this study, we
      synthesized a BODIPY TR-labeled fluorescent capsaicin analog (CHK-884) so that we
      could directly measure ligand entry. We report that CHK-884 penetrated only
      slowly into Chinese hamster ovary (CHO) cells expressing rat TRPV1, with a t1/2
      of 30 +/- 4 min, and localized in the endoplasmic reticulum and Golgi. Although
      CHK-884 was only weakly potent for TRPV1 binding (Ki = 6400 +/- 230 nM), it was
      appreciably more potent when assayed by intracellular calcium imaging and was 3.2
      fold more potent with a 1-h incubation time (37 nM) than with a 5-min incubation
      time. Olvanil, a highly lipophilic vanilloid, yielded an EC50 of 4.3 nM upon
      intracellular calcium imaging with an incubation time of 1 h, compared with an
      EC50 value of 29.5 nM for calcium imaging assayed at 5 min. Likewise, the
      antagonist 5-iodo-resiniferatoxin (5-iodo-RTX) displayed a Ki of 4.2 pM if
      incubated with CHO-TRPV1 cells for 2 h before addition of capsaicin compared with
      1.5 nM if added simultaneously. We conclude that some vanilloids may have slow
      kinetics of uptake; this slow uptake may affect assessment of structure activity
      relations and may represent a significant factor for vanilloid drug design.

PMID- 16418339
TI  - On the mechanism of interaction of potent surmountable and insurmountable
      antagonists with the prostaglandin D2 receptor CRTH2.
AB  - Chemoattractant receptor-homologous molecule expressed on T helper 2 cells
      (CRTH2) has attracted interest as a potential therapeutic target in inflammatory
      diseases. Ramatroban, a thromboxane A2 receptor antagonist with clinical efficacy
      in allergic rhinitis, was recently found to also display potent CRTH2
      antagonistic activity. Here, we present the pharmacological profile of three
      ramatroban analogs that differ chemically from ramatroban by either a single
      additional methyl group (TM30642), or an acetic acid instead of a propionic acid
      side chain (TM30643), or both modifications (TM30089). All three compounds bound
      to human CRTH2 stably expressed in human embryonic kidney 293 cells with
      nanomolar affinity. [3H]Prostaglandin D2 (PGD2) saturation analysis reveals that
      ramatroban and TM30642 decrease PGD2 affinity, whereas TM30643 and TM30089
      exclusively depress ligand binding capacity (Bmax). Each of the three compounds
      acted as potent CRTH2 antagonists, yet the nature of their antagonism differed
      markedly. In functional assays measuring inhibition of PGD2-mediated 1) guanosine
      5'-O-(3-thio)triphosphate binding, 2) beta-arrestin translocation, and 3) shape
      change of human eosinophils endogenously expressing CRTH2, ramatroban, and
      TM30642 produced surmountable antagonism and parallel rightward shifts of the
      PGD2 concentration-response curves. For TM30643 and TM30089, this shift was
      accompanied by a progressive reduction of maximal response. Binding analyses
      indicated that the functional insurmountability of TM30643 and TM30089 was
      probably related to long-lasting CRTH2 inhibition mediated via the orthosteric
      site of the receptor. A mechanistic understanding of insurmountability of CRTH2
      antagonists could be fundamental for development of this novel class of anti
      inflammatory drugs.

PMID- 16418342
TI  - Maintenance of certification: a rocky start to an important initiative.

PMID- 16418343
TI  - Strategy and economics: an overview of the Neuroradiology Education and Research
      Foundation and its activities.

PMID- 16418344
TI  - Dose delivery accuracy from (32)P-oligodeoxynucleotide-coated coils and
      associated risks of usage in humans.

PMID- 16418345
TI  - "Epidural" vertebral venous plexus.

PMID- 16418346
TI  - Platelet receptors.

PMID- 16418348
TI  - Endovascular carotid stenting in patients scheduled for cardiac surgery: if yes,
      which first?

PMID- 16418347
TI  - Presumed bilateral lateral geniculate nuclei ischemia.

PMID- 16418349
TI  - Quantification of carotid stenosis on CT angiography.
AB  - PURPOSE: Carotid artery stenosis quantification uses percent diameter ratios from
      conventional angiography. Multidetector high-speed CT angiography (CTA) allows
      direct millimeter measurement of carotid stenosis. We hypothesize a linear
      relationship between millimeter stenosis measurements and derived percent,
      alleviating cumbersome ratio calculations. METHODS: Two neuroradiologists
      separately reviewed CTAs of 268 carotid arteries, blinded to other information.
      The narrowest portion of each carotid stenosis was measured in millimeters from
      axial source images. Distal internal carotid arteries (ICAs) were measured beyond
      the bulb, where walls are parallel. North American Symptomatic Carotid
      Endarterectomy Trial (NASCET)-style ratios were calculated for each ICA, except
      for suspected near-occlusions. Interobserver agreement was calculated for all
      measurements. Correlation coefficients were calculated comparing millimeter and
      derived percent stenosis, followed by regression analysis. Sensitivity and
      specificity values tested validity. RESULTS: Interobserver agreement correlations
      were excellent, from 0.78 to 0.89 (2-tailed P </= .01). Excellent reader
      correlation permitted averaging of millimeter stenosis and distal ICA
      measurements, which were then used to calculate mean percent stenosis. Stenosis
      assessment was confidently performed from source images even with calcification.
      Regression analysis of mean percent as a function of mean millimeter stenosis
      shows a linear relationship, correlating 1.3 mm to 70% and 2.2 mm to 50% NASCET
      style stenosis (Pearson's correlation of -0.95; n = 136). Direct millimeter
      measurement defining severe stenosis (70% or greater) has sensitivity of 88.2%,
      specificity of 92.4%, and negative predicted value of 98.2%. CONCLUSION: There is
      a linear relationship between millimeter carotid stenosis diameter and derived
      percent stenosis. This allows prediction of NASCET-type percent from millimeter
      stenosis.

PMID- 16418350
TI  - First-pass quantitative CT perfusion identifies thresholds for salvageable
      penumbra in acute stroke patients treated with intra-arterial therapy.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether, in
      acute stroke patients treated with intra-arterial (IA) recanalization therapy, CT
      perfusion (CTP) can distinguish ischemic brain tissue destined to infarct from
      that which will survive. METHODS: Dynamic CTP was obtained in 14 patients within
      8 hours of stroke onset, before IA therapy. Initial quantitative cerebral blood
      volume (CBV) and flow (CBF) values were visually segmented and normalized in the
      "infarct core" (region 1: reduced CBV and CBF, infarction on follow-up),
      "penumbra that infarcts" (region 2: normal CBV, reduced CBF, infarction on follow
      up), and "penumbra that recovers" (region 3: normal CBV, reduced CBF, normal on
      follow-up). Normalization was accomplished by dividing the ischemic region of
      interest value by that of a corresponding, contralateral, uninvolved region,
      which resulted in CBV and CBF "ratios." Separate CBV and CBF values were obtained
      in gray matter (GM) and white matter (WM). RESULTS: Mean CBF ratios for regions
      1, 2, and 3 were 0.19 +/- 0.06, 0.34 +/- 0.06, and 0.46 +/- 0.09, respectively
      (all P < .001). Mean CBV ratios for regions 1, 2, and 3 were similarly distinct
      (all P < .05). Absolute CBV and CBF values for regions 2 and 3 were not
      significantly different. All regions with CBF ratio <0.32, CBV ratio <0.68, CBF
      <12.7 mL/100 g/min, or CBV <2.2 mL/100 g infarcted. No region with CBF ratio
      >0.44 infarcted. GM versus WM CBF and CBV values were significantly different for
      region 2 compared with region 3 (P < .05). CONCLUSIONS: In acute stroke patients,
      quantitative CTP can distinguish ischemic tissue likely to infarct from that
      likely to survive.

PMID- 16418351
TI  - Vasospasm after subarachnoid hemorrhage: utility of perfusion CT and CT
      angiography on diagnosis and management.
AB  - PURPOSE: To evaluate the utility of perfusion CT (PCT) combined with CT
      angiography (CTA) for the diagnosis and management of vasospasm, by using
      conventional digital subtraction angiography (DSA) as the gold standard. METHODS:
      We retrospectively identified 27 patients with acute subarachnoid hemorrhage who
      had undergone CTA/PCT, DSA, and transcranial Doppler (TCD) ultrasonography within
      a time interval of 12 hours of one another. The patients' charts were reviewed
      for treatment of vasospasm. CTA, PCT, TCD, and DSA examinations were
      independently reviewed and quantified for vasospasm. PCT thresholds, CTA
      findings, noncontrast CT (NCT) hypodensities, and TCD thresholds were evaluated
      for accuracy, sensitivity, and specificity, as well as for negative (NPV) and
      positive predictive values (PPV) in the prediction of angiographic vasospasm and
      endovascular treatment, considering DSA as the gold standard. RESULTS: Thirty
      five CTA/PCT, TCD, and DSA examinations were performed on these 27 patients. A
      total of 123 arterial territories in 11 patients demonstrated angiographic
      vasospasm. Six patients underwent endovascular therapy. CTA qualitative
      assessment and PCT-derived mean transit time (MTT) with a threshold at 6.4
      seconds represented the most accurate (93%) combination for the diagnosis of
      vasospasm, whereas MTT considered alone represented the most sensitive parameter
      (NPV, 98.7%). A cortical regional cerebral blood flow value </=39.3 (mL x 100 g(
      1)x min(-1)) represented the most accurate (94.8%) indicator for endovascular
      therapy. PCT had significantly higher PPV (89.9%) than TCD (62.9%). CONCLUSIONS:
      A CT survey combining CTA and PCT represents an accurate screening test in
      patients with suspected vasospasm. However promising, the value of PCT for
      selecting the best management strategy in such patients will need to be further
      investigated.

PMID- 16418352
TI  - Contribution of diffusion-weighted imaging in determination of stroke etiology.
AB  - INTRODUCTION: Diffusion-weighted (DW) MR imaging enables early identification of
      ischemic lesions in stroke. Stroke subtype may be related to different lesion
      patterns. The aim of this study was to analyze the subtype of ischemic lesions as
      determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria
      by using DW MR imaging. METHODS AND RESULTS: In this study, 510 consecutive
      patients with ischemic stroke (95%) and transient ischemic attack (5%) aged 65 +/
      12 years were investigated by use of DW MR imaging within 48 hours of the
      clinical onset of symptoms. Lesions on DW imaging were classified as single,
      scattered, or multiple lesions in one vascular territory and multiple in more
      than one vascular territory. We found a significant overall association of DW
      imaging lesion patterns and classification with stroke subtype by using the TOAST
      criteria (P < .001). Single corticosubcortical lesions (P < .01) and multiple
      bilateral lesions in the anterior (AC) and posterior circulation (P < .001) on DW
      imaging were significantly associated with a cardiac embolic source. Multiple
      unilateral lesions in the AC were significantly associated with large-artery
      arteriosclerosis. Because of the 15-mm criterion for small-artery occlusion,
      cryptogenic stroke was significantly associated with subcortical lesions >/=15
      mm. CONCLUSION: We found a strong relationship between stroke subtype and DW
      imaging lesion pattern. The finding of multiple bilateral lesions was
      significantly associated with a cardiac embolic source, which may be caused by a
      specific thrombus texture with a tendency for embolus dissemination.

PMID- 16418353
TI  - Effect of CT acquisition parameters in the detection of subtle hypoattenuation in
      acute cerebral infarction: a phantom study.
AB  - BACKGROUND AND PURPOSE: We evaluated the effects of varying tube voltage, current
      per rotation, and section thickness on detectability of 2- and 4-Hounsfield unit
      (HU) differences on brain CT between normal and ischemic gray matter within 6
      hours of ischemia onset, by using a low-contrast phantom. METHODS: The phantom
      with an attenuation of 36 HU corresponding to normal gray matter contained 2 sets
      of spheres (34 HU and 32 HU) corresponding to the early CT signs of ischemic
      brain and complete infarction, respectively. The reproducibility of the CT
      numbers and the contrast-to-noise ratio (CNR), defined as the CT number
      difference between the background (36 HU) and the spheres (34 HU or 32 HU)
      divided by the SD of the background CT number were measured. Five radiologists
      rated the phantom images for detection of the low-contrast spheres by visual
      inspection. RESULTS: The CT numbers were reproducible within 1 HU with a tube
      current of > or =150 mAs at 120 kVp. The CNRs for the 34- and 32-HU spheres were
      positively correlated with the tube voltage, tube current per rotation, and the
      section thickness. A CNR of 1.0 was obtained for the 34-HU sphere when scanning
      was conducted with a section thickness of 10 mm at 120 kVp and 700 mAs, or 135kVp
      and 450 mAs, respectively. A significant improvement of the accuracy of detection
      was found with increasing tube current, tube voltage per rotation, and section
      thickness. CONCLUSION: Our study indicated that the 2-HU hypoattenuation
      corresponding to the early CT sign of acute ischemic stroke can be detected by
      using appropriate parameter settings.

PMID- 16418354
TI  - Influence of partial volume on venous output and arterial input function.
AB  - BACKGROUND: CT perfusion (CTP) is an important diagnostic tool for the imaging of
      cerebral hemodynamics. To obtain quantitative values of cerebral blood volume
      (CBV), blood flow (CBF), and mean transit time (MTT), measurement of the arterial
      input function (AIF) is required. To correct for partial volume effects (PVEs),
      it is common to normalize the AIF with respect to the venous output function
      (VOF). This correction assumes that measurement of the VOF is unhampered by PVEs.
      The purpose of this study was to evaluate the effect of PVE on the measurement of
      the AIF and VOF and, consequently, on the absolute perfusion parameters. METHODS:
      In 10 patients the mean area under the curve (AUC) of the AIF and VOF were
      quantified for 3-, 6-, and 12-mm-thick sections. Differences in the mean (1) AUC
      of the VOF, (2) AUC of the AIF, and (3) width of the AIF were compared for the 3
      section thicknesses, and the influence on the absolute values of CBV, CBF, and
      MTT were studied. RESULTS: With thinner sections, the AUC of the VOF and the AIF
      increased significantly and the width of the AIF decreased slightly. Differences
      in AUC between the 3 section thicknesses were larger for the AIF than for the
      VOF. CONCLUSION: PVEs affect not only the AIF, but also the VOF. This results in
      an overestimation of CBV and CBF when a thicker section is used. To avoid PVE,
      VOF measurements should be performed at lower section thicknesses.

PMID- 16418355
TI  - Hypoxic-ischemic brain injury in the neonatal rat model: relationship between
      lesion size at early MR imaging and irreversible infarction.
AB  - BACKGROUND AND PURPOSE: By using a neonatal rat hypoxia-ischemia (HI) model, we
      studied the relationship between lesion volume-measured by diffusion-weighted
      imaging (DWI) and T2-weighted imaging (T2WI) at an early time point-and
      irreversible infarct volume. We also evaluated the optimal apparent diffusion
      coefficient (ADC) threshold that provides the best correlation with irreversible
      infarct size. MATERIALS AND METHODS: Twenty-three neonatal rats underwent right
      common carotid artery ligation and hypoxia. MR imaging was performed 1-2 hours
      post-HI by using DWI and T2WI and at day 4 post-HI by using T2WI. Lesion volumes
      relative to whole brain (%LV) were measured on ADC maps by using different
      relative ADC thresholds 60%-80% of mean contralateral ADC and T2WI. Pearson
      correlation and multiple linear regression analysis were used to study the
      relationships between ln(%LV) at MR imaging and %LV at histopathology. RESULTS:
      At 1-2 hours post-HI, all lesion volume measurements on DWI were significantly
      correlated with the infarct volume on histopathology, with the best correlation
      attained at the 80% ADC threshold (r = 0.738; P < .001). The estimated regression
      formula was %LV on histopathology = 20.60 + 3.33 ln(%LV on 80% ADC threshold)
      (adjusted R(2) = 0.523; P < .001). Lesion volume at 1-2 hours post-HI tended to
      underestimate the final infarct volume. CONCLUSION: Early post-HI MR imaging by
      using DWI correlates moderately well with the size of irreversible infarct,
      especially when measured by using a relative ADC threshold of 80% mean
      contralateral ADC.

PMID- 16418356
TI  - Bone-subtraction CT angiography for the evaluation of intracranial aneurysms.
AB  - PURPOSE: CT angiography (CTA) has been established for detection and therapy
      planning of intracranial aneurysms. The analysis of aneurysms at the level of the
      skull base, however, remains difficult because bone prevents a free view. We
      report initial clinical results of an approach for automatic bone elimination
      from CTA data. MATERIAL AND METHODS: Before the bone-removal process 2 datasets
      are acquired: nonenhanced spiral CT with reduced dose and contrast-enhanced CTA.
      The software automatically registers the nonenhanced data onto the CTA data and
      selectively removes bone. Vascular structures, as well as brain tissue, remain
      visible. In this study, we investigated 27 patients with 29 aneurysms, 13 of
      which were located at the skull base. 3D volume-rendered images with and without
      bone removal were reviewed and compared with digital subtraction angiography by 2
      radiologists in consensus. RESULTS: All supraclinoidal aneurysms were detected on
      3D volume-rendered images of both CTA and bone-subtraction CT angiography
      (BSCTA). Four intracavernous and 3 paraclinoid aneurysms of the internal carotid
      artery were not visible or were only partially visible on conventional 3D CTA,
      whereas they could be optimally visualized with BSCTA. Bone removal was
      successful in all patients; the average additional time for postprocessing was
      6.2 minutes. In 7 patients (26%), perfect bone removal without any artifacts was
      achieved. In most patients, some bone remnants were still present, though it did
      not disturb the 3D visualization of vascular structures. CONCLUSION: BSCTA allows
      robust and fast selective elimination of bony structures, thus ascertaining a
      better analysis of arteries at the level of the skull base. This is useful for
      both detection and therapy planning of intracranial aneurysms.

PMID- 16418357
TI  - Minimizing clip artifacts in multi CT angiography of clipped patients.
AB  - PURPOSE: To optimize the multi CTA (MSCTA) protocol, the influence of pitch,
      kilovoltage peak (kVp), reconstruction algorithm, type, and orientation of the
      clip on clip-induced artifacts was investigated in a phantom study. Also, the
      influence of kVp, concentration of contrast material, and clip orientation in
      clipped patients was studied. METHODS: A phantom containing a clip was scanned
      with varying parameters. Artifact was quantified with 3D volumetry. Artifact
      volumes were compared for the different parameters. In addition, the number of
      artifact streaks was presented as a function of the pitch. Five clipped patients
      were scanned with 90 kVp and 120 kVp and 5 with 120 kVp and 140 kVp. The artifact
      area was compared. The visualization at the clip site was evaluated for different
      clip orientations in 50 patients, and for 140 kVp with 370 mg iodine/mL contrast
      (I/mL) compared with 120 kVp/300 mg I/mL in 7 patients. RESULTS: Up to a pitch of
      0.6, there was hardly an increase in artifact. Higher kVp and linear
      interpolation resulted in fewer artifacts. Alloy clips containing cobalt produced
      more artifact than did titanium clips. Clips positioned perpendicular to the scan
      plane led to significantly less artifact. In patients with clips, scanning with
      140 kVp/370 mgI/mL led to a decrease of artifact area and a better visualization
      of the clip site. The visualization at the clip site was also better for clips
      perpendicular to the scan plane. CONCLUSIONS: If clip artifacts are to be
      minimized, we suggest scanning with a pitch of 0.6, by using 140 kVp and 370
      mgI/mL contrast.

PMID- 16418358
TI  - Acute and chronic brain infarcts on MR imaging in a 20-year-old woman with acute
      posterior multifocal placoid pigment epitheliopathy.
AB  - A 20-year-old woman recently diagnosed with acute posterior multifocal placoid
      pigment epitheliopathy developed headaches, weakness, and paresthesias. MR
      imaging of the brain revealed an acute infarct (demonstrated by diffusion
      weighted images) in the head of the right caudate nucleus, a chronic infarct with
      encephalomalacia in the body of the corpus callosum, and multiple foci of
      abnormal signal intensity in the white matter of the centrum semiovale.

PMID- 16418359
TI  - Line-scan diffusion tensor imaging of the posttraumatic brain stem: changes with
      neuropathologic correlation.
AB  - Following trauma, imaging of brain stem lesions is often inconclusive. In a man
      who suffered a lethal accident, postmortem MR diffusion tensor (DT) imaging of
      the brain and neuropathologic examination were performed. DT imaging showed a
      disorganization of fibers in the brain stem that was not found in 2 controls and
      corresponded to changes on neuropathologic correlation. Diffusion tensor imaging
      provides an insight into the organization of myelinated structures of the CNS,
      potentially allowing diagnosis of traumatic fiber tract rupture.

PMID- 16418360
TI  - Imaging characteristics of the subdural evacuating port system, a new bedside
      therapy for subacute/chronic subdural hematoma.
AB  - The Subdural Evacuating Port System is a new device intended to simplify the
      treatment of subacute/chronic subdural hematomas. The appearance of the winged
      canula positioned with its tip in the diploic space overlying the subdural space
      should allow the radiologist to identify it correctly. Its radiographic features
      are described here to help the radiologist comment on appropriate placement, and
      avoid mistaking it for a misplaced subdural drain.

PMID- 16418361
TI  - Intracranial compartment volumes in normal pressure hydrocephalus: volumetric
      assessment versus outcome.
AB  - BACKGROUND AND PURPOSE: Although enlargement of the cerebral ventricles plays a
      central role in the diagnosis of normal pressure hydrocephalus (NPH), there are
      no reports on the use of volumetric assessment to distinguish between patients
      who respond to ventriculoperitoneal shunt surgery and those who do not. The
      purpose of this study is to explore the association between preoperative
      intracranial compartment volumes and postoperative improvement. METHODS: Twenty
      six patients (17 men; mean age, 75 years [range, 54-87 years]) with a clinical or
      radiologic suspicion of NPH were included in the study. Gait, cognition, and
      bladder function were evaluated by clinical rating. MR imaging of the brain was
      acquired at 0.5 T and 1.5 T. Total intracranial volume, ventricular volume, brain
      volume, and pericerebral CSF volume were determined by volumetric assessment.
      Four imaging variables were determined: ventricular volume ratio, brain volume
      ratio, pericerebral CSF volume ratio, and the ratio of ventricular volume to
      pericerebral CSF volume. All patients underwent ventriculoperitoneal shunt
      surgery. RESULTS: Clinical follow-up was assessed 1 year after shunt surgery. No
      difference in the mean ventricular volume ratio, the mean brain volume ratio, the
      mean pericerebral CSF volume ratio, and the mean ratio between ventricular and
      pericerebral CSF volume was found between subjects who improved on gait or
      cognition or bladder function and those who did not. CONCLUSION: Volumetric
      assessment has no predictive value in differentiating between NPH patients who
      respond to ventriculoperitoneal shunt surgery and those who do not.

PMID- 16418362
TI  - Direct visualization of the human subthalamic nucleus with 3T MR imaging.
AB  - BACKGROUND AND PURPOSE: Electrical stimulation of the subthalamic nucleus (STN)
      is an accepted treatment for advanced Parkinson disease (PD). Although procedural
      details are well established, targeting STN remains problematic because of its
      variable location and relatively small size (20-30 mm(3)). A combination of
      anatomic imaging with a stereotactic frame, atlas coordinates, and intraoperative
      neurophysiology is currently considered the most reliable approach for STN
      targeting. CT imaging is dependent on atlas coordinates, because the STN is not
      visualized. The STN is also difficult to visualize directly by using MR imaging
      at 1.5 T. METHODS: We performed preoperative stereotactic MR imaging at 3T to
      visualize the STN in 13 patients undergoing deep-brain stimulation for PD. With
      the patient positioned within a standard Leksell type G stereotactic frame
      localizer, rapidly acquired scout images are used to prescribe volumes of
      contiguous high-resolution T2-weighted fast spin-echo images in the axial,
      sagittal, and coronal planes through the midbrain and basal ganglia. The STN is
      identified in all 3 planes by cross-referencing in a 3-plane viewer. These
      coordinates are used for surgical targeting. RESULTS: At 3T, the STN was
      visualized as a small, hypointense, almond-shaped structure in 3 planes located
      immediately lateral to the anterior edge of the red nucleus, medial to the
      internal capsule, about 5 mm inferior, 1-2 mm posterior, and 9-12 mm lateral to
      the midcommissural point. Intraoperative microelectrode recordings confirmed
      these coordinates in all cases from the first microelectrode pass, thereby
      eliminating prolonged intraoperative electrophysiological STN searching and
      tissue disruption that may occur from multiple passes. CONCLUSION: 3T MR imaging
      appears to be an excellent tool for reliable and accurate direct visualization of
      the human STN, necessary for precise surgical targeting.

PMID- 16418363
TI  - Perfusion imaging of meningioma by using continuous arterial spin-labeling:
      comparison with dynamic susceptibility-weighted contrast-enhanced MR images and
      histopathologic features.
AB  - PURPOSE: The goal of the present study was to determine the utility of continuous
      arterial spin labeling (CASL) for characterization of meningioma by MR perfusion
      imaging and to compare these results with those obtained from the T2 dynamic
      susceptibility contrast (T2DSC) method and from histopathologic examination.
      METHODS: Twenty-one cases of meningiomas were examined at 1.5T. CASL perfusion
      imaging was implemented on the basis of multisection single-shot echo-planar
      imaging with velocity-driven adiabatic spin-inversion preparation. T2DSC
      perfusion imaging was also performed by using a double-echo spoiled gradient echo
      sequence in a section containing the tumor. By focusing on the regions of
      interest, maps of % signal intensity change and cerebral blood flow (CBF) were
      determined from CASL and cerebral blood volume (CBV). CBF and mean transit time
      (MTT) were obtained from T2DSC. The microvessel area (MVA) was determined from
      specimens immunostained with anti-CD31 in 14 cases by measuring the total amount
      of staining in each histologic section. Linear regression analysis was performed
      for rCBF values from both perfusion methods and for % signal intensity change and
      MVA. RESULTS: There was a significant correlation between CBF values determined
      from both perfusion methods (r(2) = 0.73; P < .001); however, the slope from
      T2DSC to CASL was less than unity, likely because of the different vascular
      weighting used for each method. There was also a significant correlation between
      CASL-% signal intensity change and MVA determined by histopathology (r(2) = 0.91;
      P < .00001). Perfusion values were the greatest for angiomatous meningioma and
      lowest for fibrous meningioma when using either perfusion method. CONCLUSIONS:
      CASL and T2DSC perfusion methods are comparable in the characterization of
      meningiomas. Further, CASL is of use in assessing tumor microcirculation.

PMID- 16418364
TI  - Perfusion MR imaging of an intracranial collision tumor confirmed by image-guided
      biopsy.
AB  - We present a patient with a new intracranial mass lesion that was initially
      interpreted as a metastasis on conventional anatomic MR imaging. On dynamic,
      contrast-enhanced, susceptibility-weighted perfusion MR imaging, however, there
      were regional hemodynamic differences within the lesion. Image-guided open biopsy
      targeting these regions uncovered a collision tumor between a typical meningioma
      and a metastatic breast carcinoma. In cases where conventional anatomic MR
      imaging is ambiguous, physiology-based neuroimaging methods provide complementary
      physiologic information useful for discriminating between histologically unique
      tissue types.

PMID- 16418365
TI  - Neuropsychological and perfusion MR imaging correlates of revascularization in a
      case of moyamoya syndrome.
AB  - Serial neurocognitive and perfusion MR imaging findings are described in the
      perioperative course of a 48-year-old woman with a superficial temporal artery to
      middle cerebral artery bypass for right hemispheric ischemia due to moyamoya
      syndrome. Neurocognitive testing reflected both global and focal cerebrovascular
      dysfunction, which suggests that perfusion augmentation following surgical
      revascularization may engender cognitive and neurologic improvement beyond focal
      regions of established ischemia.

PMID- 16418366
TI  - Correlation between initial and early follow-up CT perfusion parameters with
      endoscopic tumor response in patients with advanced squamous cell carcinomas of
      the oropharynx treated with organ-preservation therapy.
AB  - BACKGROUND AND PURPOSE: Current organ-preservation regimens for upper
      aerodigestive tract squamous cell carcinoma (SCCA) require endoscopic procedures
      under general anesthesia to evaluate the tumor response. The purpose of our study
      was to determine whether CT perfusion (CTP) parameters correlate with response to
      induction chemotherapy as assessed by endoscopy under general anesthesia.
      METHODS: Nine patients with advanced (stage 3 or 4) SCCA of the oropharynx were
      enrolled in a nested phase 2 prospective trial in which induction chemotherapy
      was used to assess the tumor response. Patients underwent direct laryngoscopy and
      CTP before and 3 weeks after one cycle of induction chemotherapy. The outcome
      variables were the surgeon's estimate of tumor volume during endoscopy with
      biopsy under anesthesia and CTP parameters (capillary permeability (CP), blood
      volume (BV), blood flow (BF), and mean transit time (MTT)). Wilcoxon rank sum
      analysis was used to correlate the baseline values of BF and BV with response to
      induction chemotherapy. Comparison of agreement between the reduction in tumor
      volume and change in CTP parameters was performed by using kappa estimates.
      RESULTS: Seven of 9 patients demonstrated > or =50% tumor volume reduction,
      representing positive response to induction chemotherapy. In the responder group,
      the following changes in mean pre- and postinduction chemotherapy values were
      noted: mean BF, 114.2 mL/100 g /min (preinduction) to 45.1 mL/100 g/min
      (postinduction); mean BV, 5.11 mL/100 g to 3.1 mL/100 g; mean CP, 25.6 mL/100 g
      /min (preinduction) to 18.3 mL/100 g / min (postinduction); mean MTT, 4.9 seconds
      (preinduction) to 8.0 seconds (postinduction). In the nonresponder group, the
      following changes were noted: mean BF, 56.9 mL/100 g/min to 75.9 mL/100 g/min;
      mean, BV 2.7 mL/100 g to 4.71 mL/100 g; mean CP, 24.1 mL/100 g/min to 23.7 mL/100
      g/min; mean MTT, 4.3 seconds to 5.34 seconds. Higher baseline (pretherapy) values
      of BV showed significant correlation with endoscopic tumor response (P < .05).
      Reduction in the BV (by >/=20%) on follow-up studies also showed substantial
      agreement with clinical response as assessed with endoscopy (kappa = 0.73). The
      agreement between decreased BF, decreased CP, and increased MTT and clinical
      response was fair (kappa = 0.37). CONCLUSION: These preliminary results show that
      deconvolution-based CTP technique offers potential for noninvasive monitoring of
      response to induction chemotherapy in patients with oropharyngeal cancers.
      Percentage reduction of BV is significantly correlated to endoscopic response to
      induction chemotherapy, though we acknowledge that the data correspond to short
      term outcomes and long-term durability of response cannot be established.
      Nevertheless, validation of the use of deconvolution CTP parameters as predictors
      of tumor response may permit replacement of an invasive diagnostic procedure
      conducted under anesthesia currently used to assess response with noninvasive
      perfusion CT imaging.

PMID- 16418367
TI  - Relative value of sliding-thin-slab multiplanar reformations and sliding-thin
      slab maximum intensity projections as reformatting techniques in multisection CT
      angiography of the cervicocranial vessels.
AB  - BACKGROUND AND PURPOSE: To investigate image quality and vascular delineation of
      multisection CT (MSCT) angiography of the cervicocranial vessels with sliding
      thin-slab (STS) maximum intensity projections (MIP) and multiplanar reformations
      (MPR). MATERIALS AND METHODS: Ten patients examined with a standardized protocol
      on a 16-section MSCT were included in the study. The data were reformatted as MIP
      and MPR in 3 planes for each subject; both reformatting techniques were applied
      in an STS technique with an increment of 3 mm. Images were evaluated
      independently by 3 blinded readers grading image quality parameters and vascular
      delineation of supra-aortic arteries and veins. An extension of the Mantel
      Haenzel row mean score test was used to compare the distribution of scores for
      vascular delineation and image quality between STS MIP and STS MPR. RESULTS: STS
      MIP reformations were significantly superior to STS MPR in the delineation of all
      extra- and intracranial arteries and arterial segments and in the delineation of
      the cavernous sinus and the internal cerebral veins (P < .05). No significant
      differences were found for the large venous vessels, the visual assessment of
      vascular contrast, or the impact of imaging artifacts. CONCLUSION: Because STS
      MIP reformations were preferred to or equal to STS MPR in all aspects, we
      recommend STS MIP as the primary reformatting technique in MSCT angiography of
      the cervicocranial vessels in addition to viewing the source images.

PMID- 16418368
TI  - A potential pitfall of MR imaging for assessing mandibular invasion of squamous
      cell carcinoma in the oral cavity.
AB  - BACKGROUND AND PURPOSE: Whether MR imaging is superior to CT in evaluating the
      presence and extent of mandibular invasion by squamous cell carcinoma remains
      controversial. The purpose of this study was to directly compare the diagnostic
      accuracy of MR imaging and that of CT. METHODS: MR and CT images in 51 patients
      with squamous cell carcinoma of the oral cavity were evaluated for the presence
      and extent of mandibular invasion. The results were correlated with
      histopathologic findings. RESULTS: Twenty-five of 51 patients had histopathologic
      evidence of mandibular cortical invasion. The tumor involved both the cortex and
      the bone marrow in all 25 patients and involved the inferior alveolar canal in 5
      patients. The sensitivity and specificity for mandibular cortical invasion were
      96% and 54% for MR imaging and 100% and 88% for CT, respectively. Those for
      inferior alveolar canal involvement were 100% and 70% for MR imaging and 100% and
      96% for CT, respectively. In both evaluations, the specificity of MR imaging was
      significantly lower than that of CT (McNemar test, P = .004 in the former and P =
      .002 in the latter). Chemical shift artifact by bone marrow fat was postulated to
      be the source of most false-positive cases on MR imaging findings for mandibular
      cortical invasion. Those for inferior alveolar canal involvement were due to MR
      imaging visualization of the tumor and surrounding inflammation with similar
      signal intensity. CONCLUSION: In assessing the presence and extent of mandibular
      invasion by squamous cell carcinoma, the specificity of MR imaging was
      significantly lower than that of CT.

PMID- 16418369
TI  - Chondrosarcoma of the hyoid bone: imaging, surgical, and histopathologic
      correlation.
AB  - Chondrosarcoma of the hyoid bone is rare. Only 14 cases have been reported in the
      literature, to date. We present a case of chondrosarcoma of the hyoid bone with
      imaging, surgical, and pathologic correlation, and a review of the literature.

PMID- 16418370
TI  - CT features of plexiform neurofibroma of the submandibular gland.
AB  - Plexiform neurofibroma of the submandibular gland is an extremely rare tumor. We
      report the CT findings in a 6-year-old girl with type 1 neurofibromatosis who had
      a histopathologically proven submandibular gland plexiform neurofibroma. A
      "branching" hypodense mass was noted on the CT scan infiltrating the
      submandibular gland and the adjacent spaces of the neck. CT could be extremely
      valuable in suggesting the diagnosis.

PMID- 16418371
TI  - Anomalous intracranial drainage of the nasal mucosa: a vein of the foramen
      caecum?
AB  - The existence of the vein of the foramen caecum (VFC) in humans is still
      controversial. We present 2 patients with intracranial drainage of the nasal
      mucosa by a frontal cortical vein into a superior sagittal sinus, demonstrated by
      digital subtraction angiography. In both, the position of the intracranial
      passage was found to be slightly paramedian. An analogy to the VFC is made.

PMID- 16418372
TI  - A proposed ordinal scale for grading histology in elastase-induced, saccular
      aneurysms.
AB  - BACKGROUND AND PURPOSE: The elastase-induced aneurysm model in rabbits, though
      widely applied, still offers no quantitative or qualitative metric for histologic
      outcome. This study is aimed at producing such a scale to evaluate outcome and
      facilitate meaningful, preclinical comparison among devices proposed for aneurysm
      treatment. MATERIAL AND METHOD: Elastase-induced aneurysms were created and
      embolized in 30 rabbits. Aneurysms were harvested between 2 and 24 weeks.
      Specimens were embedded in paraffin, sectioned, and stained with hematoxylin and
      eosin. The scale comprised 3 subcategories: extent and degree of
      recanalization/coil compaction; neck healing, based on thickness and type of
      tissue across the neck; and dome healing. Neck healing was assessed by both gross
      and microscopic inspections. Compaction was assessed by using both the
      angiographic and histologic images. Dome healing was assessed by using the
      microscopic images only. Data were analyzed with either analysis of variance for
      the quantitative data or Kruskal-Wallis tests when analyzing the nonparametric
      data. RESULTS: We noted a significant main effect for healing over time (P =
      .0016). Post hoc tests showed that, at 2 weeks, the mean score was 1.4 +/- 0.8,
      as compared with a mean score of 7.2 +/- 1.6 for the 24-week time point (P < or =
      .05). Further, significant differences in healing between narrow-necked (6.0 +/-
      1.3) and wide-necked aneurysms (3.5 +/- 1.1) were seen at 4 weeks (P = .0433).
      The dynamic range of the scale also appears to be appropriate, because there was
      adequate range at the upper portion of the scale to reflect improved healing that
      might be achieved with future devices. CONCLUSIONS: This scale is a potentially
      relevant outcome measurement tool for elastase-induced aneurysms after
      endovascular therapy. Future studies are still required to confirm its practical
      relevance.

PMID- 16418373
TI  - Long-term patency of elastase-induced aneurysm model in rabbits.
AB  - BACKGROUND AND PURPOSE: Long-term patency in untreated experimental aneurysms
      represents a critical attribute of any system proposed for the testing of
      aneurysm occlusion devices. Our purpose was to evaluate the long-term patency in
      elastase-induced saccular aneurysm models in rabbits. METHODS: Serial intravenous
      digital subtractive angiography (IVDSA) was performed in 20 elastase-induced
      saccular aneurysm models in rabbits 1, 3, 6, 9, 12, and 24 months after creation.
      Aneurysm dimensions, including neck diameter, width, and height, were measured
      and calculated from IVDSA images. Comparisons of the aneurysm sizes across time
      were performed by using the paired Wilcoxon signed rank test and the Friedman
      test. RESULTS: None of the 20 aneurysms showed spontaneous thrombosis at any time
      point. Mean dimensions did not change over time for any parameter. Mean aneurysm
      neck, width, and height were not significantly changed at interval evaluations of
      1, 3, 6, 9, 12, and 24 months (P = .210; P = .413, and P = .405, respectively).
      CONCLUSION: Long-term patency in elastase-induced saccular aneurysm models in
      rabbits is excellent. Aneurysm dimensions remain stable for as long as 2 years
      following creation.

PMID- 16418374
TI  - Endovascular treatment of intracranial aneurysms with a branch arising from the
      sac.
AB  - BACKGROUND AND PURPOSE: The endovascular treatment (EVT) of intracranial
      aneurysms is no more limited by the presence of a branch at the neck or by the
      neck width. Saccular aneurysms with a branch arising from the sac, however, are
      mostly candidates for surgery rather than embolization. We prospectively
      evaluated the feasibility and safety of the EVT in such cases. METHODS: Between
      May and November 2004, 9 consecutive patients with a saccular aneurysm that
      presents a branch arising from the sac were treated by embolization. There were 7
      women and 2 men (mean age, 58 years). Six patients presented with a subarachnoid
      hemorrhage (SAH), and 3 were asymptomatic. All patients were treated by selective
      coiling with (n = 6) or without (n = 3) the remodeling technique. Clinical
      outcome was assessed with a modified Glasgow Outcome Scale at 3 months. RESULTS:
      EVT was successfully performed in all patients and resulted in 7 excellent
      outcomes and 2 deaths related to SAH complications. The arterial branch could be
      preserved in 7 cases and intentionally occluded in 2. Neither embolic nor
      ischemic complication occurred in the vascular territory of the involved branch.
      Angiographic results showed 5 neck remnants, 2 incomplete occlusions, and 2
      complete occlusions. No rebleeding occurred. CONCLUSION: Our study, though
      limited by its small patient population, suggests that saccular intracranial
      aneurysms with a branch arising from the sac may be treated by endovascular
      approach with excellent clinical results; however, larger series with long-term
      follow-up are mandatory to confirm these preliminary results mostly in terms of
      anatomic stability.

PMID- 16418375
TI  - Occlusion of the middle cerebral artery due to synthetic fibers.
AB  - We report an unusual etiology for a thromboembolic complication. Occlusion of the
      middle cerebral artery occurred before embolization of an intracranial aneurysm.
      Attempts to recanalize the artery failed by using both fibrinolytics and IIb/IIIa
      inhibitors but succeeded with mechanical thrombectomy with a micro-snare.
      Pathologic analysis of the thrombus showed numerous synthetic fibers that were
      determined to have originated from unsealed gauze that was used during the
      procedure.

PMID- 16418376
TI  - Spontaneous improvement of persistent ulceration after carotid artery stenting.
AB  - BACKGROUND AND PURPOSE: Because carotid plaque ulceration is associated with an
      increased risk of cerebral embolism, residual carotid plaque ulceration directly
      around a stent (persistent ulceration) after carotid angioplasty and stent
      placement (CAS) could still be a risk factor for a stroke. The purpose of this
      study is to understand the morphologic and clinical prognosis of persistent
      ulceration. PATIENTS AND TECHNIQUES: CAS was attempted on 91 consecutive stenotic
      lesions (80 patients). Of these, 54 lesions (48 patients) had ulceration before
      CAS. Angiograms were evaluated immediately after the procedure. Persistent
      ulceration was found in 34 lesions (30 patients). The mean depth and length of
      persistent ulcers were 2.1 mm (range, 1-4.7 mm) and 8.9 mm (range, 1.5-22 mm),
      respectively. All patients with persistent ulceration were followed with
      antiplatelet therapy. RESULTS: No ischemic event due to the lesions occurred
      during the mean follow-up period of 25.5 months (range, 3-48 months). Angiography
      on 25 lesions (21 patients) at a mean of 5.8 months (range, 1-21 months) after
      CAS showed that persistent ulceration disappeared in 12 lesions (48%), improved
      in 11 lesions (44%), and remained unchanged in 2 lesions (8%). Nine lesions (36%)
      showed restenosis, which were < or =30% and did not require any additional
      intervention. New ischemic lesions were not detected in any of the 14 patients
      (17 lesions) who underwent follow-up MR imaging at a mean of 9 months (range, 1
      32 months) after CAS. CONCLUSION: We conclude that persistent ulceration after
      CAS improves spontaneously and is not a risk factor for cerebral embolism.

PMID- 16418377
TI  - The amount of solid cerebral microemboli during carotid stenting does not relate
      to the frequency of silent ischemic lesions.
AB  - BACKGROUND AND PURPOSE: Carotid artery stent placement (CAS) may be associated
      with clinically silent cerebral lesions. We prospectively evaluated the
      association of the number of solid cerebral microemboli during unprotected CAS
      with the frequency of silent cerebral lesions as detected by diffusion-weighted
      MR imaging (DWI). METHODS: We performed multifrequency transcranial Doppler
      detection of solid microemboli in the ipsilateral middle cerebral artery (MCA)
      during CAS in 27 consecutive patients with symptomatic high-grade carotid
      stenoses. No embolus protection was used in any of the cases. DWI before and 24
      +/- 2 hours after CAS was used to detect new ischemic lesions. RESULTS: We
      detected 484 solid microemboli in 17 patients (63%). On MR imaging 24 +/- 2 hours
      after CAS, 6 patients (22%) had developed 13 new clinically silent DWI lesions
      within the ipsilateral MCA territory. In patients with Doppler evidence of solid
      emboli during CAS, the incidence of new DWI lesions was higher (29%) than in
      patients without Doppler evidence of solid emboli during the procedure (10%);
      this difference was not statistically significant (P = .25). The number of solid
      microemboli during CAS in patients with new ipsilateral DWI lesions was not
      significantly different from that in patients without new ipsilateral DWI
      lesions. CONCLUSIONS: Solid microembolism is a common event during unprotected
      CAS; however, the frequency of procedure-related silent cerebral lesions appears
      to be independent of the number of solid cerebral microemboli during the
      procedure.

PMID- 16418378
TI  - Endovascular treatment of intracerebral arteriovenous malformations: procedural
      safety, complications, and results evaluated by MR imaging, including diffusion
      and perfusion imaging.
AB  - BACKGROUND AND PURPOSE: Endovascular embolization is an increasingly common
      method to treat intracerebral arteriovenous malformations (AVM). To date,
      however, published data are rather scarce, especially with regard to true
      procedure-related complications and their causes. The purpose of our study was to
      evaluate treatment safety and correlate anatomic results with clinical outcome by
      using MR imaging, including diffusion-weighted (DWI) and perfusion imaging (PI).
      METHODS: We performed 50 endovascular procedures in 21 patients. Most AVMs were
      supratentorial, Spetzler-Martin grades II-IV. MR imaging was scheduled within 1
      week before and 3 days after each treatment. MR imaging findings were correlated
      to digital subtraction angiography, procedure reports, and the clinical course.
      Outcome was graded according to the modified Rankin scale (mRS) 3-6 months after
      treatment. RESULTS: In this study, 104 MR imaging examinations were performed;
      mean interval between the endovascular procedure and posttreatment MR imaging was
      28 hours. Nine adverse events occurred in 7 patients during 8 procedures (16%),
      one causing a permanent deficit. New lesions were noted on MR imaging after 22/50
      procedures. Ischemic lesions in 22% of the procedures, frequently located
      perinidally. Most lesions were small, frequently asymptomatic, and reversible
      (18/23). Four hematomas were found. Subacute hemorrhages developed from a
      vasogenic edema on 2 occasions. New lesions, including hematomas, developed
      between treatments in 4 patients, mainly because of progressive occlusion of the
      nidus or draining veins. PI overestimated the AVM nidus on most occasions, and
      transient worsening of the PI pattern was noted in 2 patients. Treatment-related
      mortality and morbidity were 0% and 14.2%, respectively (mRS 1-2). CONCLUSIONS:
      Endovascular procedures are rather safe but are associated with more ischemic
      events and followed by less hemodynamic disturbances than previously understood.
      Adverse procedural events and new MR imaging lesions were generally asymptomatic
      and most often transient, if symptomatic. Most lesions would not have been
      verified without MR imaging. DWI and PI were most useful to detect and understand
      the cause of various complications. The most clinically important complications
      were caused by late venous occlusions.

PMID- 16418379
TI  - In vitro evaluation of 2D-digital subtraction angiography versus 3D-time-of
      flight in assessment of intracranial cerebral aneurysm filling after endovascular
      therapy.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate 2D-digital
      subtraction angiographic (DSA) and 3D-time-of-flight (TOF) MR imaging in
      assessment of aneurysmal residue by using a pulsating silicon aneurysm model. For
      each imaging system, we studied intra- and interobserver reproducibility and the
      agreement between interpretations and reference measurements. We also examined
      how each imaging technique affected the operator's therapeutic decision. METHODS:
      Two silicon aneurysm models depicting subarachnoidal aneurysms were used, one
      with a wide neck and one with a narrow neck. Each aneurysm model was placed in
      series on a pulsed flow circuit and was filled with Guglielmi detachable coils to
      simulate a clinical case. Each aneurysm was then gradually filled with silicon
      gel in increments of 10%, up to 100% to simulate different levels of occlusion
      (residual neck or dog ear, partial, complete) at each filling level. For each
      level of filling, we performed conventional 2D-DSA and 3D-TOF MR imaging. We
      submitted the images for examination by 2 senior medical staff with 2 readings
      per image. A combined reading of the 2 images was submitted to each expert to
      determine whether the 2 examinations were complementary. RESULTS: The 2D-DSA
      analysis showed good reproducibility (k = 0.8 and k = 0.57) and agreement (k =
      0.71) in describing "complete" treatments. The distinction between a "residual
      neck" and "partial treatment," however, was not reliable. The 2D-DSA provided a
      good description of the coil and silicon protrusion into the parent artery. The
      3D-TOF analysis of the residual aneurysm, however, was not reproducible, though
      it was more effective than the 2D-DSA in evaluation of partially wide-necked
      aneurysms (k = 0.68 MR imaging vs k = 0.041 2D-DSA; P = .018). At the same
      filling level, the 2D-DSA analysis indicated repeat treatment more often than 3D
      TOF analysis (P = .059). CONCLUSION: The 2D-DSA remains the gold standard, but MR
      imaging is more effective in evaluating a "partial treatment." The 2D-DSA
      analysis indicated repeat treatment more often than the 3D-TOF for the same
      occlusion level. The distinction between "partial treatment" and a "residual
      neck" was not reliable with either method of evaluation.

PMID- 16418380
TI  - Ruptured cavernous sinus aneurysms causing carotid cavernous fistula: incidence,
      clinical presentation, treatment, and outcome.
AB  - BACKGROUND AND PURPOSE: In this study, we present our experience with 11 patients
      with ruptured cavernous sinus aneurysms causing carotid cavernous fistulas
      (CCFs), to assess the incidence of ruptured cavernous sinus aneurysms causing
      CCFs and evaluate clinical presentations, treatments, and outcomes. PATIENTS AND
      METHODS: During a 10-year period, 10 of 689 (1.5%) endovascular-treated ruptured
      aneurysms were ruptured cavernous sinus aneurysms causing CCF. One additional
      patient with a CCF died shortly before treatment of intracranial hemorrhage. All
      patients had audible pulsatile bruit. Exophthalmus, ocular motor palsy, and
      decreased vision correlated with venous drainage to the superior ophthalmic veins
      and intracerebral hemorrhage was associated with major cortical venous drainage
      in 2 patients. RESULTS: Two low-flow CCFs closed spontaneously before treatment
      with resolution of symptoms; the aneurysms were subsequently treated. Eight CCFs
      were successfully occluded, 5 by coil occlusion of the aneurysm, one by occlusion
      of the aneurysm with a balloon, and 2 by simultaneous coil occlusion of the
      aneurysm and internal carotid artery. There were no complications of treatment.
      Visual acuity returned to normal in all but one patient, and ophthalmoplegia was
      cured in 6 of 8 patients. In 2 patients, a remaining abducens palsy was
      surgically corrected. CONCLUSION: The incidence of CCF by a ruptured cavernous
      sinus aneurysm was 1.5%. CCF was the presenting symptom in 24.4% of treated
      symptomatic cavernous sinus aneurysms. Clinical symptoms correlate with venous
      drainage. Drainage to cortical veins may lead to intracranial hemorrhage.
      Endovascular treatment with coils is effective in occluding the fistula.

PMID- 16418381
TI  - Balloon-assisted coiling through a single 6F guiding catheter.
AB  - The new version of the 6F Envoy guiding catheter, with its enlarged inner
      diameter of 0.070 inch, is capable of simultaneously accommodating both a 0.014
      inch microcatheter and a balloon microcatheter for balloon-assisted coiling
      (BAC). We report our experience using this guiding catheter for access in BAC in
      48 patients. The guiding catheter allowed for easy manipulations of 2
      microcatheters, while providing sufficient quality of control angiograms during
      the procedure. In cases in which BAC is indicated, a larger guiding catheter (7F)
      or the commonly used bifemoral approach is no longer necessary, making the
      procedure technically simpler for the operator and less traumatic to the vessel
      wall.

PMID- 16418382
TI  - MR imaging and angiography of primary CNS vasculitis of childhood.
AB  - BACKGROUND AND PURPOSE: Primary angiitis of the central nervous system of
      childhood (cPACNS) is a rare and ill-defined disease. In the absence of a brain
      biopsy, the diagnosis is based on typical clinical and imaging abnormalities. The
      aim of this study was to analyze systematically the MR imaging and MR
      angiographic (MRA) abnormalities in a large cohort of children with cPACNS.
      METHODS: We analyzed the MR imaging features of a single pediatric center cohort
      of 45 cPACNS patients. MR imaging studies were performed for all patients, and
      both MR imaging and MRA were performed for 42 patients, who formed the cohort for
      review of the presence and correlation of lesions. Proportions were calculated by
      using the Fisher exact test, and agreement between MR imaging and MRA was
      calculated by using the McNemar test. The sensitivity of each diagnostic
      technique was established. RESULTS: The most-common pattern of parenchymal
      abnormality was multifocal, unilateral involvement, each in 42/45 patients (93%).
      The lateral lenticulostriate artery terrritory was affected in 56% of cases, with
      involvement of a supratentorial deep gray matter structure in 91%. No
      infratentorial lesion occurred in the absence of supratentorial abnormality. MRA
      was normal in 12/42 patients (28.6%). Among the abnormal studies, stenosis was
      detected on MRA in 83% and was "benign" in appearance in 73% of patients and
      "aggressive" in 16.7%. Involvement was proximal in 83% and distal in 27% of
      patients. Multiple ipsilateral lesions were seen in 63%. MR imaging was abnormal
      in every patient where MRA was abnormal. With the assumption of MR imaging as the
      gold standard, the sensitivity of MRA was 72%. The agreement between MR imaging
      and MRA for abnormality was significant (P = .04). CONCLUSION: We have
      illustrated the MR imaging and MRA appearances of cPACNS in the largest cohort to
      date. Both parenchymal and vascular lesions were predominantly proximal,
      unilateral, and multifocal within the anterior circulation. There was good
      agreement between MR imaging and MRA for lesion location. MR imaging findings
      were abnormal in all cases at diagnosis, and this remains the most sensitive
      technique to the detection of vasculitis.

PMID- 16418383
TI  - Leukoencephalopathy, cerebral calcifications, and cysts.
AB  - Association of leukoencephalopathy, cerebral calcifications, and cysts (LCC) is a
      rare disorder that was recently described. To our knowledge, only 2 reports,
      including 3 patients in each, have been published in the literature to date.
      Herein, we report a 19-year-old man with LCC who had neurological symptoms
      beginning in late adolescence. Clinically, he had rare convulsive seizures,
      slowly progressive pyramidal symptoms, and normal intelligence. On radiological
      examination, there were progressive calcifications in the basal nuclei and the
      cerebral white matter, as well as parenchymal cysts and diffuse abnormal signals
      of the white matter on T2-weighted sequences on MR imaging. On histopathological
      examination, angiomatous changes and secondary gliosis were demonstrated.

PMID- 16418384
TI  - Proton MR spectroscopy and imaging of a galactosemic patient before and after
      dietary treatment.
AB  - We describe how proton MR spectroscopy ((1)H-MR spectroscopy) was useful in
      elucidating the diagnosis of galactosemia in an undiagnosed 6-month-old infant.
      In vivo (1)H-MR spectroscopy of the brain showed a doublet at 3.7 parts per
      million, which was identified as galactitol (Gal-ol) by in vitro (1)H-MR
      spectroscopy of the urine. Galactosemia was subsequently confirmed by laboratory
      tests and treatment was initiated. A follow-up brain MR imaging and (1)H-MR
      spectroscopy study revealed resolution of white matter lesions and disappearance
      of Gal-ol peaks.

PMID- 16418385
TI  - Sequential MR imaging changes in nonketotic hyperglycinemia.
AB  - Serial diffusion-weighted (DWI) and diffusion tensor imaging (DTI) were performed
      in a patient with neonatal onset nonketotic hyperglycinemia (NKH). At 3 weeks
      areas that are normally myelinated at this time showed increased T2-signal
      intensity and restricted diffusion, consistent with vacuolating myelinopathy. At
      3 months, these areas had increased in the topographic pattern of normal
      myelination, whereas fractional anisotropy was compatible with axonal sparing. At
      17 months, diffusion restriction had disappeared, likely because of coalescence
      of myelin vacuoles. A decrease of fractional anisotropy was observed in the
      previously myelinated areas indicative of axonal loss. We conclude that DWI and
      DTI can be used to identify and characterize white matter tract abnormalities in
      patients with NKH.

PMID- 16418386
TI  - Pantothenate kinase-associated neurodegeneration with increased lentiform nuclei
      cerebral blood flow.
AB  - We report a case of pantothenate kinase-associated neurodegeneration with
      increased regional cerebral blood flow (rCBF) in bilateral lentiform nuclei on
      technetium Tc-99m ethyl cysteinate dimer single-photon emission CT (ECD-SPECT). A
      6-year-old boy presented with opisthotonus. T2*-weighted MR images revealed areas
      of marked hypointensity with a hyperintense focus in bilateral globus pallidus,
      creating the characteristic eye-of-the-tiger appearance. ECD-SPECT showed
      increased rCBF in bilateral lentiform nuclei.

PMID- 16418387
TI  - MR diffusion tensor imaging and fiber tracking in 5 spinal cord astrocytomas.
AB  - Spinal cord astrocytomas are rare neoplasms that can result in alteration of the
      spinal cord structural integrity, which can be assessed by using diffusion tensor
      imaging methods. Our objective was to visualize the deformation of the posterior
      spinal cord lemniscal and corticospinal tracts in 5 patients with low-grade
      astrocytomas compared with 10 healthy volunteers by using 3D fiber-tracking
      reconstructions.

PMID- 16418388
TI  - New fractures after vertebroplasty: adjacent fractures occur significantly
      sooner.
AB  - BACKGROUND AND PURPOSE: Whether vertebroplasty increases the risk of adjacent
      level vertebral fractures remains uncertain. Biomechanical and clinical studies
      suggest an increased risk, but compelling data have not yet been put forth to
      settle this difficult issue. We believe that an analysis of the time interval
      between vertebroplasty and subsequent fractures may shed additional light on this
      debate. We specifically hypothesized that subsequent fractures would occur sooner
      and more frequently in the vertebrae adjacent to the treated level. METHODS: We
      performed a retrospective analysis of the risk and timing of subsequent fractures
      in patients previously treated with vertebroplasty. Multiple linear regression
      was used to explore factors that influence the time to new fracture following
      vertebroplasty. Fractures were then divided on the basis of whether they occurred
      adjacent or non-adjacent to the treated level. Survival analysis was used to
      compare time to new fracture among the 2 groups, and the relative risk of both
      types of fracture was calculated. RESULTS: In this study, 186 new vertebral
      fractures occurred in 86 (19.9%) of 432 patients. Seventy-seven (41.4%) fractures
      were of vertebrae adjacent to the level treated with vertebroplasty. Median times
      until diagnosis of new adjacent and non-adjacent level fractures were 55 days and
      127 days, respectively. Time to fracture was significantly different between the
      2 groups (logrank <0.0001). Distance of the new fracture from the treated level
      was also significantly associated with time to new fracture (P < .0001). Relative
      risk of adjacent level fracture was 4.62 times that for non-adjacent level
      fracture. CONCLUSION: These data demonstrate an association between
      vertebroplasty and new vertebral fractures. Specifically, following
      vertebroplasty, patients are at increased risk of new-onset adjacent-level
      fractures and, when these fractures occur, they occur sooner than non-adjacent
      level fractures.

PMID- 16418390
TI  - Refracture with cement extrusion following percutaneous vertebroplasty of a large
      interbody cleft.
AB  - We present a case report of a patient on long-term dialysis who underwent
      percutaneous vertebroplasty to treat a painful intrabody vertebral cleft and who
      subsequently experienced a refracture of the posterior portion of the same
      vertebral body, resulting in anterior displacement of the cement through the
      anterior cortex. The case raises the question whether, in some patients, the
      marrow space should be filled with cement in addition to the cleft.

PMID- 16418389
TI  - Intraspinal leakage of bone cement after vertebroplasty: a report of 3 cases.
AB  - We report 3 cases of vertebroplasty-induced intraspinal leakage of bone cement
      that were referred to us for management. Two patients received decompressive
      surgery, and one received rehabilitation. The gross surgical finding of yellowish
      dura mater and intradural fibrosis, adhesion, and microscopic finding of
      arachnoid membrane fibrosis are suggestive of late effect of thermal injury.
      These patients had residual lower extremity weakness and urinary and stool
      problems 13 months, 3 years, and 4.75 years post-vertebroplasty, respectively.

PMID- 16418391
TI  - Percutaneous laser disk decompression: a review of the literature.

PMID- 16418392
TI  - TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the
      atherosclerotic plaque.
AB  - Acute coronary syndromes (ACS) are precipitated by a rupture of the
      atherosclerotic plaque, often at the site of T cell and macrophage infiltration.
      Here, we show that plaque-infiltrating CD4 T cells effectively kill vascular
      smooth muscle cells (VSMC). VSMCs sensitive to T cell-mediated killing express
      the death receptor DR5 (TNF-related apoptosis-inducing ligand [TRAIL] receptor
      2), and anti-TRAIL and anti-DR5 antibodies block T cell-mediated apoptosis. CD4 T
      cells that express TRAIL upon stimulation are expanded in patients with ACS and
      more effectively induce VSMC apoptosis. Adoptive transfer of plaque-derived CD4 T
      cells into immunodeficient mice that are engrafted with human atherosclerotic
      plaque results in apoptosis of VSMCs, which was prevented by coadministration of
      anti-TRAIL antibody. These data identify that the death pathway is triggered by
      TRAIL-producing CD4 T cells as a direct mechanism of VSMC apoptosis, a process
      which may lead to plaque destabilization.

PMID- 16418393
TI  - Nod1 acts as an intracellular receptor to stimulate chemokine production and
      neutrophil recruitment in vivo.
AB  - Nod1 is a member of family of intracellular proteins that mediate host
      recognition of bacterial peptidoglycan. To characterize immune responses mediated
      by Nod1, synthetic ligand compounds possessing enhanced ability to stimulate Nod1
      were developed to study the function of Nod1. Stimulation of epithelial cells
      with Nod1 stimulatory molecules induced chemokines and other proinflammatory
      molecules that are important for innate immune responses and recruitment of acute
      inflammatory cells. Administration of Nod1 ligands into mice induced chemokines
      and recruitment of acute inflammatory cells, an activity that was abolished in
      Nod1-null mice. Microarray analysis revealed that Nod1 stimulation induces a
      restricted number of genes in intestinal epithelial cells compared with that
      induced by tumor necrosis factor (TNF) alpha. Nod1 stimulation did not induce
      TNFalpha, interleukin 12, and interferon gamma, suggesting that the primary role
      of Nod1 is to induce the recruitment of immune cells. These results indicate that
      Nod1 functions as a pathogen recognition molecule to induce expression of
      molecules involved in the early stages of the innate immune response.

PMID- 16418394
TI  - Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon
      induced anti-HIV-1 activity.
AB  - Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G), a
      cytidine deaminase, is a recently recognized innate intracellular protein with
      lethal activity against human immunodeficiency virus (HIV). Packaged into progeny
      virions, APOBEC3G enzymatic activity leads to HIV DNA degradation. As a
      counterattack, HIV virion infectivity factor (Vif) targets APOBEC3G for
      proteasomal proteolysis to exclude it from budding virions. Based on the ability
      of APOBEC3G to antagonize HIV infection, considerable interest hinges on
      elucidating its mechanism(s) of regulation. In this study, we provide the first
      evidence that an innate, endogenous host defense factor has the potential to
      promote APOBEC3G and rebuke the virus-mediated attempt to control its cellular
      host. We identify interferon (IFN)-alpha as a potent inducer of APOBEC3G to
      override HIV Vif neutralization of APOBEC3 proteins that pose a threat to
      efficient macrophage HIV replication. Our data provide a new dimension by which
      IFN-alpha mediates its antiviral activity and suggest a means to render the host
      nonpermissive for viral replication.

PMID- 16418395
TI  - Activation of the Flt3 signal transduction cascade rescues and enhances type I
      interferon-producing and dendritic cell development.
AB  - Flt3 ligand (Flt3L) is a nonredundant cytokine in type I interferon-producing
      cell (IPC) and dendritic cell (DC) development, and IPC and DC differentiation
      potential is confined to Flt3+ hematopoietic progenitor cells. Here, we show that
      overexpression of human Flt3 in Flt3- (Flt3(-)Lin(-)IL-7Ralpha(-)Thy1.1(-)c-Kit+)
      and Flt3+ (Flt3(+)Lin(-)IL-7Ralpha(-)Thy1.1(-)c-Kit+) hematopoietic progenitors
      rescues and enhances their IPC and DC differentiation potential, respectively. In
      defined hematopoietic cell populations, such as Flt3- megakaryocyte/erythrocyte
      restricted progenitors (MEPs), enforced Flt3 signaling induces transcription of
      IPC, DC, and granulocyte/macrophage (GM) development-affiliated genes, including
      STAT3, PU.1, and G-/M-/GM-CSFR, and activates differentiation capacities to these
      lineages. Moreover, ectopic expression of Flt3 downstream transcription factors
      STAT3 or PU.1 in Flt3- MEPs evokes Flt3 receptor expression and instructs
      differentiation into IPCs, DCs, and myelomonocytic cells, whereas GATA-1
      expression and consecutive megakaryocyte/erythrocyte development is suppressed.
      Based on these data, we propose a demand-regulated, cytokine-driven DC and IPC
      regeneration model, in which high Flt3L levels initiate a self-sustaining, Flt3
      STAT3- and Flt3-PU.1-mediated IPC and DC differentiation program in Flt3+
      hematopoietic progenitor cells.

PMID- 16418396
TI  - AID-dependent histone acetylation is detected in immunoglobulin S regions.
AB  - Class switch recombination (CSR) is regulated by the expression of activation
      induced deaminase (AID) and germline transcripts (GLTs). AID-dependent double
      strand breaks (DSBs) are introduced into switch (S) regions and stimulate CSR.
      Although histone acetylation (Ac) has been well documented in transcription
      regulation, its role in DNA damage repair remains largely unexplored. The 1B4.B6
      B cell line and normal splenic B cells were activated to undergo CSR and analyzed
      for histone Ac by chromatin immunoprecipitation (ChIP). A detailed study of the
      Igamma3-Sgamma3-Cgamma3 locus demonstrated that acetylated histones are focused
      to the Igamma3 exon and the Sgamma3 region but not to the intergenic areas.
      Histone H3 Ac is strongly correlated with GLT expression at four S regions,
      whereas H4 Ac was better associated with B cell activation and AID expression. To
      more directly examine the relationship between H4 Ac and AID, LPS-activated AID
      KO and WT B cells were analyzed and express comparable levels of GLTs. In AID
      deficient B cells, both histones H3 and H4 are reduced where H4 is more severely
      affected as compared with WT cells. Our findings raise the intriguing possibility
      that histone H4 Ac at S regions is a marker for chromatin modifications
      associated with DSB repair during CSR.

PMID- 16418397
TI  - Stoichiometry of the murine gammadelta T cell receptor.
AB  - The T cell receptor for antigen (TCR) complex is organized into two functional
      domains: the antigen-binding clonotypic heterodimer and the signal-transducing
      invariant CD3 and TCRzeta chains. In most vertebrates, there are two different
      clonotypic heterodimers (TCRalphabeta and TCRgammadelta) that define the
      alphabeta and gammadelta T cell lineages, respectively. alphabeta- and
      gammadeltaTCRs also differ in their invariant chain subunit composition, in that
      alphabetaTCRs contain CD3gammaepsilon and CD3deltaepsilon dimers, whereas
      gammadeltaTCRs contain only CD3gammaepsilon dimers. This difference in subunit
      composition of the alphabeta- and gammadeltaTCRs raises the question of whether
      the stoichiometries of these receptor complexes are different. As the
      stoichiometry of the murine gammadeltaTCR has not been previously investigated,
      we used two quantitative immunofluorescent approaches to determine the valency of
      TCRgammadelta heterodimers and CD3gammaepsilon dimers in surface murine
      gammadeltaTCR complexes. Our results support a model of murine gammadeltaTCR
      stoichiometry in which there are two CD3gammaepsilon dimers for every
      TCRgammadelta heterodimer.

PMID- 16418398
TI  - CCR5 deficiency increases risk of symptomatic West Nile virus infection.
AB  - West Nile virus (WNV) is a reemerging pathogen that causes fatal encephalitis in
      several species, including mouse and human. Recently, we showed that the
      chemokine receptor CCR5 is critical for survival of mice infected with WNV,
      acting at the level of leukocyte trafficking to the brain. To test whether this
      receptor is also protective in man, we determined the frequency of CCR5Delta32, a
      defective CCR5 allele found predominantly in Caucasians, in two independent
      cohorts of patients, one from Arizona and the other from Colorado, who had
      laboratory-confirmed, symptomatic WNV infection. The distribution of CCR5Delta32
      in a control population of healthy United States Caucasian random blood donors
      was in Hardy-Weinberg equilibrium and CCR5Delta32 homozygotes represented 1.0% of
      the total group (n = 1,318). In contrast, CCR5Delta32 homozygotes represented
      4.2% of Caucasians in the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence
      interval [CI], 1.6-11.8], P = 0.0013) and 8.3% of Caucasians in the Colorado
      cohort (OR = 9.1 [95% CI, 3.4-24.8], P < 0.0001). CCR5Delta32 homozygosity was
      significantly associated with fatal outcome in the Arizona cohort (OR = 13.2 [95%
      CI, 1.9-89.9], P = 0.03). We conclude that CCR5 mediates resistance to
      symptomatic WNV infection. Because CCR5 is also the major HIV coreceptor, these
      findings have important implications for the safety of CCR5-blocking agents under
      development for HIV/AIDS.

PMID- 16418400
TI  - Gating of acid-sensitive ion channel-1: release of Ca2+ block vs. allosteric
      mechanism.
AB  - The acid-sensitive ion channels (ASICs) are a family of voltage-insensitive
      sodium channels activated by external protons. A previous study proposed that the
      mechanism underlying activation of ASIC consists of the removal of a Ca2+ ion
      from the channel pore (Immke and McCleskey, 2003). In this work we have revisited
      this issue by examining single channel recordings of ASIC1 from toadfish
      (fASIC1). We demonstrate that increases in the concentration of external protons
      or decreases in the concentration of external Ca2+ activate fASIC1 by
      progressively opening more channels and by increasing the rate of channel
      opening. Both maneuvers produced similar effects in channel kinetics, consistent
      with the former notion that protons displace a Ca2+ ion from a high-affinity
      binding site. However, we did not observe any of the predictions expected from
      the release of an open-channel blocker: decrease in the amplitude of the unitary
      currents, shortening of the mean open time, or a constant delay for the first
      opening when the concentration of external Ca2+ was decreased. Together, the
      results favor changes in allosteric conformations rather than unblocking of the
      pore as the mechanism gating fASIC1. At high concentrations, Ca2+ has an
      additional effect that consists of voltage-dependent decrease in the amplitude of
      unitary currents (EC50 of 10 mM at -60 mV and pH 6.0). This phenomenon is
      consistent with voltage-dependent block of the pore but it occurs at
      concentrations much higher than those required for gating.

PMID- 16418399
TI  - Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors
      and facilitates acquisition of protective immunity.
AB  - Uptake of Leishmania major by dendritic cells (DCs) results in activation and
      interleukin (IL)-12 release. Infected DCs efficiently stimulate CD4- and CD8- T
      cells and vaccinate against leishmaniasis. In contrast, complement receptor 3
      dependent phagocytosis of L. major by macrophages (MPhi) leads exclusively to MHC
      class II-restricted antigen presentation to primed, but not naive, T cells, and
      no IL-12 production. Herein, we demonstrate that uptake of L. major by DCs
      required parasite-reactive immunoglobulin (Ig)G and involved FcgammaRI and
      FcgammaRIII. In vivo, DC infiltration of L. major-infected skin lesions coincided
      with the appearance of antibodies in sera. Skin of infected B cell-deficient mice
      and Fcgamma-/- mice contained fewer parasite-infected DCs in vivo. Infected B
      cell-deficient mice as well as Fcgamma-/- mice (all on the C57BL/6 background)
      showed similarly increased disease susceptibility as assessed by lesion volumes
      and parasite burdens. The B cell-deficient mice displayed impaired T cell priming
      and dramatically reduced IFN-gamma production, and these deficits were normalized
      by infection with IgG-opsonized parasites. These data demonstrate that DC and
      MPhi use different receptors to recognize and ingest L. major with different
      outcomes, and indicate that B cell-derived, parasite-reactive IgG and DC
      FcgammaRI and FcgammaRIII are essential for optimal development of protective
      immunity.

PMID- 16418401
TI  - Direct observation of a preinactivated, open state in BK channels with beta2
      subunits.
AB  - Proteins arising from the Slo family assemble into homotetramers to form
      functional large-conductance, Ca2+- and voltage-activated K+ channels, or BK
      channels. These channels are also found in association with accessory beta
      subunits, which modulate several aspects of channel gating and expression.
      Coexpression with either of two such subunits, beta2 or beta3b, confers time
      dependent inactivation onto BK currents. mSlo1+beta3b channels display
      inactivation that is very rapid but incomplete. Previous studies involving
      macroscopic recordings from these channels have argued for the existence of a
      second, short-lived conducting state in rapid equilibrium with the nonconducting,
      inactivated conformation. This state has been termed "pre-inactivated," or O*.
      beta2-mediated inactivation, in contrast, occurs more slowly but is virtually
      complete at steady state. Here we demonstrate, using both macroscopic and single
      channel current recordings, that a preinactivated state is also a property of
      mSlo1+beta2 channels. Detection of this state is enhanced by a mutation (W4E)
      within the initial beta2 NH2-terminal segment critical for inactivation. This
      mutation increases the rate of recovery to the preinactivated open state,
      yielding macroscopic inactivation properties qualitatively more similar to those
      of beta3b. Furthermore, short-lived openings corresponding to entry into the
      preinactivated state can be observed directly with single-channel recording. By
      examining the initial openings after depolarization of a channel containing beta2
      W4E, we show that channels can arrive directly at the preinactivated state
      without passing through the usual long-lived open conformation. This final result
      suggests that channel opening and inactivation are at least partly separable in
      this channel. Mechanistically, the preinactivated and inactivated conformations
      may correspond to binding of the beta subunit NH2 terminus in the vicinity of the
      cytoplasmic pore mouth, followed by definitive movement of the NH2 terminus into
      a position of occlusion within the ion-conducting pathway.

PMID- 16418403
TI  - Summaries for patients. Exercise in people age 65 years and older is associated
      with lower risk for dementia.

PMID- 16418402
TI  - Membrane-delimited inhibition of maxi-K channel activity by the intermediate
      conductance Ca2+-activated K channel.
AB  - The complexity of mammalian physiology requires a diverse array of ion channel
      proteins. This diversity extends even to a single family of channels. For
      example, the family of Ca2+-activated K channels contains three structural
      subfamilies characterized by small, intermediate, and large single channel
      conductances. Many cells and tissues, including neurons, vascular smooth muscle,
      endothelial cells, macrophages, and salivary glands express more than a single
      class of these channels, raising questions about their specific physiological
      roles. We demonstrate here a novel interaction between two types of Ca2+
      activated K channels: maxi-K channels, encoded by the KCa1.1 gene, and IK1
      channels (KCa3.1). In both native parotid acinar cells and in a heterologous
      expression system, activation of IK1 channels inhibits maxi-K activity. This
      interaction was independent of the mode of activation of the IK1 channels: direct
      application of Ca2+, muscarinic receptor stimulation, or by direct chemical
      activation of the IK1 channels. The IK1-induced inhibition of maxi-K activity
      occurred in small, cell-free membrane patches and was due to a reduction in the
      maxi-K channel open probability and not to a change in the single channel current
      level. These data suggest that IK1 channels inhibit maxi-K channel activity via a
      direct, membrane-delimited interaction between the channel proteins. A
      quantitative analysis indicates that each maxi-K channel may be surrounded by
      four IK1 channels and will be inhibited if any one of these IK1 channels opens.
      This novel, regulated inhibition of maxi-K channels by activation of IK1 adds to
      the complexity of the properties of these Ca2+-activated K channels and likely
      contributes to the diversity of their functional roles.

PMID- 16418404
TI  - Summaries for patients. The relationship of socioeconomic status and health
      status to outcomes following heart attack.

PMID- 16418405
TI  - Summaries for patients. Tamoxifen for the treatment of retroperitoneal fibrosis.

PMID- 16418406
TI  - Exercise is associated with reduced risk for incident dementia among persons 65
      years of age and older.
AB  - BACKGROUND: Alzheimer disease and other dementing disorders are major sources of
      morbidity and mortality in aging societies. Proven strategies to delay onset or
      reduce risk for dementing disorders would be greatly beneficial. OBJECTIVE: To
      determine whether regular exercise is associated with a reduced risk for dementia
      and Alzheimer disease. DESIGN: Prospective cohort study. SETTING: Group Health
      Cooperative, Seattle, Washington. PARTICIPANTS: 1740 persons older than age 65
      years without cognitive impairment who scored above the 25th percentile on the
      Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought
      study and who were followed biennially to identify incident dementia.
      MEASUREMENTS: Baseline measurements, including exercise frequency, cognitive
      function, physical function, depression, health conditions, lifestyle
      characteristics, and other potential risk factors for dementia (for example,
      apolipoprotein E epsilon4); biennial assessment for dementia. RESULTS: During a
      mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107
      developed Alzheimer disease). The incidence rate of dementia was 13.0 per 1000
      person-years for participants who exercised 3 or more times per week compared
      with 19.7 per 1000 person-years for those who exercised fewer than 3 times per
      week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% CI, 0.44
      to 0.86; P = 0.004). The interaction between exercise and performance-based
      physical function was statistically significant (P = 0.013). The risk reduction
      associated with exercise was greater in those with lower performance levels.
      Similar results were observed in analyses restricted to participants with
      incident Alzheimer disease. LIMITATIONS: Exercise was measured by self-reported
      frequency. The study population had a relatively high proportion of regular
      exercisers at baseline. CONCLUSION: These results suggest that regular exercise
      is associated with a delay in onset of dementia and Alzheimer disease, further
      supporting its value for elderly persons.

PMID- 16418407
TI  - Socioeconomic status and mortality after acute myocardial infarction.
AB  - BACKGROUND: Gradients that link socioeconomic status and cardiovascular mortality
      have been observed in many populations, including those of countries that provide
      publicly funded comprehensive medical coverage. The intermediary causes of such
      gradients remain poorly elucidated. OBJECTIVE: To examine the relationships among
      socioeconomic status, other health factors, and 2-year mortality rates after
      acute myocardial infarction (MI). DESIGN: Prospective cohort study. SETTING:
      Ontario, Canada. PATIENTS: 3407 patients who were hospitalized for acute MI in 53
      large-volume hospitals in Canada from December 1999 to February 2003.
      MEASUREMENTS: The authors obtained self-reported measures of income and education
      and developed profiles of the patients' prehospitalization cardiac risks and
      comorbid conditions. To create these profiles, the authors used the patients'
      self-reports and retrospectively linked no less than 12 years' worth of previous
      hospitalization data. Mortality rates 2 years after acute MI were examined with
      and without sequential risk adjustment for age, sex, ethnicity, social support,
      cardiovascular history and risk, comorbid conditions, and selected in-hospital
      process factors. RESULTS: Income was strongly and inversely correlated with 2
      year mortality rate (crude hazard ratio for high-income vs. low-income tertile,
      0.45 [95% CI, 0.35 to 0.57]; P < 0.001). However, after adjustment for age and
      preexisting cardiovascular events or conventional vascular risk factors, the
      effect of income was greatly attenuated (adjusted hazard ratio for high-income
      vs. low-income tertile, 0.77 [CI, 0.54 to 1.10]; P = 0.150). Noncardiovascular
      comorbid conditions and in-hospital process factors had negligible explanatory
      effect. LIMITATIONS: Previous cardiovascular risks were ascertained through self
      report or retrospectively through the longitudinal tracking of the hospitals'
      administrative databases. The study began with a cohort of patients who had an
      index cardiac event rather than with asymptomatic individuals. CONCLUSIONS: Age,
      past cardiovascular events, and current vascular risk factors accounted for most
      of the income-mortality gradient after acute MI. This observation suggests that
      the "wealth-health gradient" in cardiovascular mortality may be partially
      ameliorated by more rigorous management of known risk factors among less affluent
      persons. *For a list of members of the SESAMI Study Group, see the Appendix.

PMID- 16418408
TI  - Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.
AB  - BACKGROUND: Three point mutations (A2143G, A2142G, and A2142C) have been involved
      in Helicobacter pylori clarithromycin resistance. OBJECTIVE: To compare the
      eradication rates among the different point mutations and the efficacy of triple
      therapy and a sequential regimen according to genotypic resistance. DESIGN: Post
      hoc subgroup study from a multicenter, randomized trial. SETTING: Two hospitals
      in central and southern Italy between January and December 2001. PATIENTS: 156
      patients with H. pylori infection. MEASUREMENTS: Real-time polymerase chain
      reaction for assessing clarithromycin resistance; histology, rapid urease test,
      and 13C-urea breath test at entry and after 4 to 6 weeks. INTERVENTION: 7-day
      triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of
      amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole
      plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of
      clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81
      patients. All drugs were given twice daily. RESULTS: Helicobacter pylori
      infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and
      in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45
      percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The
      sequential regimen achieved a higher cure rate than triple therapy in A2143G
      mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points];
      P = 0.024). LIMITATIONS: The post hoc substudy design may require further
      confirmation. Other limitations are the accessibility to the tool and the cost of
      investigations (70 euros per patient). CONCLUSIONS: The A2143G mutation seemed to
      be associated with a very low eradication rate. The sequential regimen achieved a
      higher cure rate than standard therapy even in patients with these strains.

PMID- 16418409
TI  - Brief communication: tamoxifen therapy for nonmalignant retroperitoneal fibrosis.
AB  - BACKGROUND: Anecdotal case reports suggest tamoxifen as a possible treatment for
      retroperitoneal fibrosis, but a systematic assessment of its effect is not
      available. OBJECTIVE: To describe the course and outcomes of patients with
      nonmalignant retroperitoneal fibrosis treated with tamoxifen. DESIGN:
      Prospective, consecutive series. SETTING: Single tertiary care referral center.
      PATIENTS: 19 patients with nonmalignant retroperitoneal fibrosis treated with
      tamoxifen from April 1998 through April 2005. INTERVENTION: Tamoxifen, 20 mg
      orally twice daily. MEASUREMENTS: Clinical improvement, laboratory variables, and
      follow-up computed tomography (CT) and gallium scan findings. RESULTS: Fifteen
      patients reported substantial resolution of symptoms after a median treatment
      duration of 2.5 weeks. Erythrocyte sedimentation rate and C-reactive protein also
      improved. Gallium scanning at follow-up showed incomplete disappearance of
      pathologic gallium-67 activity. Repeated CT scanning showed slow but steady mass
      regression in 14 of 15 clinical responders. Five patients failed treatment,
      including 1 patient who improved clinically. Disease recurred in 1 patient who
      responded to reintroduction of tamoxifen. One patient developed reversible
      hepatitis. LIMITATIONS: This small observational study did not have a control
      group. CONCLUSION: Tamoxifen may be a viable therapeutic option in the treatment
      of retroperitoneal fibrosis.

PMID- 16418410
TI  - Problem doctors: is there a system-level solution?
AB  - Physician performance failures are not rare and pose substantial threats to
      patient welfare and safety. Few hospitals respond to such failures promptly or
      effectively. Failure to ensure the quality and safety of the performance of
      colleagues is a breach of medicine's fiduciary responsibility to the public. A
      major reason for this deficiency is the hospitals' lack of formal systems to
      monitor physician performance and to identify and correct shortcomings. To
      develop and implement these systems, hospitals need better performance measures
      and substantial expansion of external programs for assessment and remediation.
      This is a task well beyond the capacities of individual hospitals; a national
      effort is required. The authors call on the Federation of State Medical Boards,
      the American Board of Medical Specialties, and the Joint Commission on
      Accreditation of Healthcare Organizations (organizations that already bear a
      fiduciary responsibility for ensuring safe, competent care) to collaborate on
      developing better methods for measuring performance and to expand programs for
      helping practitioners who are deficient.

PMID- 16418411
TI  - Systematic review: antimicrobial urinary catheters to prevent catheter-associated
      urinary tract infection in hospitalized patients.
AB  - BACKGROUND: The efficacy of antimicrobial urinary catheters in hospitalized
      patients is poorly defined. PURPOSE: To assess currently marketed antimicrobial
      urinary catheters for preventing catheter-associated urinary tract infection
      (UTI). DATA SOURCES: Electronic databases, conference proceedings,
      bibliographies, trialists, and catheter manufacturers (search dates, 1966 to June
      2005). STUDY SELECTION: Randomized and quasi-randomized trials of nitrofurazone
      coated or silver alloy-coated antimicrobial urinary catheter use for less than 30
      days; no language restriction. DATA EXTRACTION: Study design, study sample,
      inclusion and exclusion criteria, allocation, blinding, UTI definition,
      ascertainment methods, and proportion developing symptomatic UTI (primary end
      point) or bacteriuria (secondary end point) were extracted by using a structured
      data collection instrument. DATA SYNTHESIS: Twelve qualifying trials (13,392
      total participants or catheters) were identified. They compared nitrofurazone
      coated silicone (n = 3) or silver-coated latex (n = 9) catheters with silicone or
      latex catheters. No study addressed symptomatic UTI. All trials suggested
      protection against bacteriuria with test catheter use. However, effect size
      varied considerably and postrandomization exclusions were very common. Effect
      size was greatest in trials of nitrofurazone-coated catheters (all post-1995) and
      in pre-1995 silver alloy-coated catheter trials and was smallest in post-1995
      silver alloy-coated catheter trials. Control group bacteriuria rate, control
      catheter type (latex vs. silicone), and patient sample (urology vs. other) also
      predicted effect size. Few studies addressed secondary bloodstream infection,
      mortality, costs, or microbial resistance. Short-term adverse effects were
      minimal. LIMITATIONS: The study was limited by the number, size, and quality of
      studies and by lack of the following: intention-to-treat analyses, data on
      clinical end points, and trials comparing nitrofurazone-coated with silver alloy
      coated catheters. CONCLUSIONS: According to fair-quality evidence, antimicrobial
      urinary catheters can prevent bacteriuria in hospitalized patients during short
      term catheterization, depending on antimicrobial coating and several other
      variables. Older data probably lack current relevance. Cost implications and
      effect on infectious complications remain undefined.

PMID- 16418413
TI  - Mens sana in corpore sano.

PMID- 16418414
TI  - Going back to understand the future: socioeconomic position and survival after
      myocardial infarction.

PMID- 16418415
TI  - Improving Helicobacter pylori eradication regimens.

PMID- 16418412
TI  - Acute pain management for patients receiving maintenance methadone or
      buprenorphine therapy.
AB  - More patients with opioid addiction are receiving opioid agonist therapy (OAT)
      with methadone and buprenorphine. As a result, physicians will more frequently
      encounter patients receiving OAT who develop acutely painful conditions,
      requiring effective treatment strategies. Undertreatment of acute pain is
      suboptimal medical treatment, and patients receiving long-term OAT are at
      particular risk. This paper acknowledges the complex interplay among addictive
      disease, OAT, and acute pain management and describes 4 common misconceptions
      resulting in suboptimal treatment of acute pain. Clinical recommendations for
      providing analgesia for patients with acute pain who are receiving OAT are
      presented. Although challenging, acute pain in patients receiving this type of
      therapy can effectively be managed.

PMID- 16418416
TI  - Of poems and patients.

PMID- 16418417
TI  - Aziza.

PMID- 16418418
TI  - National health information network cost and structure.

PMID- 16418419
TI  - National health information network cost and structure.

PMID- 16418420
TI  - National health information network cost and structure.

PMID- 16418421
TI  - National health information network cost and structure.

PMID- 16418422
TI  - Prevention of exacerbations of chronic obstructive pulmonary disease with
      tiotropium.

PMID- 16418423
TI  - Prevention of exacerbations of chronic obstructive pulmonary disease with
      tiotropium.

PMID- 16418424
TI  - Inhaled treprostinil [corrected] for treatment of chronic pulmonary arterial
      hypertension.

PMID- 16418425
TI  - Exorcising ghosts and unwelcome guests.

PMID- 16418426
TI  - Exorcising ghosts and unwelcome guests.

PMID- 16418427
TI  - Neurocysticercosis in Kansas.

PMID- 16418428
TI  - Health and the environment after Hurricane Katrina.

PMID- 16418429
TI  - Fathead: the gain in brain falls mainly with leptin wane.

PMID- 16418430
TI  - Female's heightened immune status: estrogen, T cells, and inducible nitric oxide
      synthase in the balance.

PMID- 16418431
TI  - The free fatty acid receptor GPR40 generates excitement in pancreatic beta-cells.

PMID- 16418433
TI  - Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin
      signaling as a biological marker of early impairment.
AB  - Impairment of hippocampal function precedes frontal and parietal cortex
      impairment in human Alzheimer's disease (AD). Neurotrophins are critical for
      behavioral performance and neuronal survival in AD. We used complex and radial
      mazes to assess spatial orientation and learning in wild-type and B6
      Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse model of AD. We also
      assessed brain content of nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF), and neurotrophin-3 (NT-3). Performance was alike in wild-type and
      APP23 animals in the radial maze. In contrast, performance in the complex maze
      was better in wild-type than APP23 animals. Contrary to the wild-type,
      hippocampal BDNF levels decreased on training in APP23 animals. Hippocampal and
      frontal cortex NGF levels in APP23 animals correlated with the time to solve the
      complex maze, but correlated inversely with escape time in wild-type animals. NT
      3 levels were alike in wild-type and APP23 animals and were unchanged even after
      training. Both types of mazes depend on hippocampal integrity to some extent.
      However, according to the cognitive mapping theory of spatial learning, the
      complex maze because of the increased complexity of the environment most likely
      depends more strongly on preserved hippocampal function than the radial maze in
      the working memory configuration applied here. Greater impairment in complex maze
      performance than in radial maze performance thus resembles the predominant
      affliction of the loss of hippocampal function in human AD. NGF and BDNF levels
      on maze learning are different in wild-type and transgenic animals, indicating
      that biological markers of AD may be altered on challenge even though equilibrium
      levels are alike.

PMID- 16418435
TI  - Electrolytic lesions of the medial prefrontal cortex do not interfere with long
      term memory of extinction of conditioned fear.
AB  - Lesion studies indicate that rats without the medial prefrontal cortex (mPFC)
      have difficulty recalling fear extinction acquired the previous day. Several
      electrophysiological studies have also supported this observation by
      demonstrating that extinction-related increases in neuronal activity in the mPFC
      participate in expression of fear extinction. However, a more recent study has
      shown that fear extinction can be recalled, in certain circumstances, without
      mPFC potentiation, suggesting contribution of other circuits. Here, we examined
      this possibility in rats that were subjected to auditory fear conditioning,
      extinction training, and extinction retention test 7 d later. Electrolytic
      lesions were made in the mPFC, the motor cortex (MO), the dorsal septum (SEP), or
      the mediodorsal thalamus (MD), because of their potential participation in
      conditioned fear inhibition; combined lesions including the mPFC with the MO,
      SEP, or MD were also made. The lesions were made either 1 wk before conditioning
      or 1 d after extinction training. All rats normally extinguished their
      conditioned freezing behavior during extinction training and did not display any
      return of this behavior during the retention test. These data reveal that the
      mPFC is not required for the acquisition, the expression, or the retrieval of
      extinction memories but do not exclude the possibility that the mPFC normally
      participates in these processes.

PMID- 16418434
TI  - Genetic dissociation of acquisition and memory strength in the heat-box spatial
      learning paradigm in Drosophila.
AB  - Memories can have different strengths, largely dependent on the intensity of
      reinforcers encountered. The relationship between reinforcement and memory
      strength is evident in asymptotic memory curves, with the level of the asymptote
      related to the intensity of the reinforcer. Although this is likely a fundamental
      property of memory formation, relatively little is known of how memory strength
      is determined. Memory performance at different levels in Drosophila can be
      measured in an operant heat-box conditioning paradigm. In this spatial learning
      paradigm, flies learn and remember to avoid one-half of a dark chamber associated
      with a temperature outside of the preferred range. The reinforcement temperature
      has a strong effect on the level of learning in wild-type flies, with higher
      temperatures inducing stronger memories. Additionally, two mutations alter memory
      acquisition curves, either changing acquisition rate or asymptotic memory level.
      The rutabaga mutation, affecting a type-1 adenylyl cyclase, decreases the
      acquisition rate. In contrast, the white mutation, modifying an ABC transporter,
      limits asymptotic memory. The white mutation does not negatively affect classical
      olfactory conditioning but actually improves performance at low reinforcement
      levels. Thus, memory acquisition/memory strength and classical olfactory/operant
      spatial memories can be genetically dissociated. A conceptual model of operant
      conditioning and the levels at which rutabaga and white influence conditioning is
      proposed.

PMID- 16418436
TI  - Hippocampal CA1 kindling but not long-term potentiation disrupts spatial memory
      performance.
AB  - Long-term synaptic enhancement in the hippocampus has been suggested to cause
      deficits in spatial performance. Synaptic enhancement has been reported after
      hippocampal kindling that induced repeated electrographic seizures or
      afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic
      enhancement without ADs. We studied whether repeated stimulations that gave LTP
      or ADs resulted in spatial performance deficits on the radial arm maze (RAM) and
      investigated the minimal number of ADs required for such deficits. Three
      experimental groups were run as follows: (1) 5 hippocampal ADs in 1 d (5-AD
      group), (2) 10 hippocampal ADs in 2 d (10-AD group), and (3) 12 -frequency primed
      burst stimulations (PBSs) in 2 d in order to induce LTP without ADs (LTP group).
      Each experimental group was run together with a control group during the same
      time period. Rats were first trained in a spatial task on a radial arm maze with
      four of the eight arms baited, then given control or experimental treatment, and
      maze performance was tested in the first week (1-4 d) and fourth week (22-25 d)
      after treatment. Basal dendritic population excitatory postsynaptic potentials
      (pEPSPs) and medial perforant path (MPP)-evoked dentate gyrus population spike
      and polysynaptic CA1 excitation were recorded before and after experimental and
      control treatment. Spatial memory errors, in particular reference memory errors,
      were significantly higher in the 10-AD kindled group than any other group on the
      first and fourth week after treatment. Spatial memory errors were not
      significantly different in the 5-AD and LTP groups as compared with any control
      groups at any time. Basal dendritic pEPSP in CA1 was enhanced for about 1 wk
      after 12 PBSs, 10 ADs, or 5 ADs, while the dentate gyrus population spike and CA1
      polysynaptic excitation evoked by MPP was increased for up to 4 wk after 10 ADs,
      but not 12 PBSs. Thus, distributed alteration of multiple synaptic transmission
      in the entorhinal-hippocampal circuit, but not LTP at the basal dendritic
      synapses in CA1, may disrupt spatial performance after 10 hippocampal ADs.

PMID- 16418437
TI  - The "prawn-in-the-tube" procedure in the cuttlefish: habituation or passive
      avoidance learning?
AB  - This study examines whether or not habituation contributes to the regulation of
      the inhibition of predatory behavior observed during the "prawn-in-the-tube"
      training procedure. When presented with prawns that are visible behind glass but
      untouchable, cuttlefish promptly learn to inhibit their capture attempts. The
      first three experiments demonstrated that the acquired response in the course of
      training cannot be dishabituated. The fourth experiment demonstrated that the
      repeated application of a brief visual prawn stimulus, one that is terminated
      before the cuttlefish can strike, decreases attack latencies. Taken together, the
      results of this study establish that habituation does not play a significant role
      in this learning task. In fact, the present findings strengthen the results of
      previous studies suggesting that passive avoidance learning contributes to the
      regulation of the inhibition of predatory behavior.

PMID- 16418440
TI  - Venous thromboembolism in children.

PMID- 16418439
TI  - Soy protein, isoflavones, and cardiovascular health: an American Heart
      Association Science Advisory for professionals from the Nutrition Committee.
AB  - Soy protein and isoflavones (phytoestrogens) have gained considerable attention
      for their potential role in improving risk factors for cardiovascular disease.
      This scientific advisory assesses the more recent work published on soy protein
      and its component isoflavones. In the majority of 22 randomized trials, isolated
      soy protein with isoflavones, as compared with milk or other proteins, decreased
      LDL cholesterol concentrations; the average effect was approximately 3%. This
      reduction is very small relative to the large amount of soy protein tested in
      these studies, averaging 50 g, about half the usual total daily protein intake.
      No significant effects on HDL cholesterol, triglycerides, lipoprotein(a), or
      blood pressure were evident. Among 19 studies of soy isoflavones, the average
      effect on LDL cholesterol and other lipid risk factors was nil. Soy protein and
      isoflavones have not been shown to lessen vasomotor symptoms of menopause, and
      results are mixed with regard to soy's ability to slow postmenopausal bone loss.
      The efficacy and safety of soy isoflavones for preventing or treating cancer of
      the breast, endometrium, and prostate are not established; evidence from clinical
      trials is meager and cautionary with regard to a possible adverse effect. For
      this reason, use of isoflavone supplements in food or pills is not recommended.
      Thus, earlier research indicating that soy protein has clinically important
      favorable effects as compared with other proteins has not been confirmed. In
      contrast, many soy products should be beneficial to cardiovascular and overall
      health because of their high content of polyunsaturated fats, fiber, vitamins,
      and minerals and low content of saturated fat.

PMID- 16418441
TI  - Images in cardiovascular medicine. Cardiac teratoma in a newborn with right
      ventricular outflow tract obstruction.

PMID- 16418438
TI  - Spatial relational memory in 9-month-old macaque monkeys.
AB  - This experiment assesses spatial and nonspatial relational memory in freely
      moving 9-mo-old and adult (11-13-yr-old) macaque monkeys (Macaca mulatta). We
      tested the use of proximal landmarks, two different objects placed at the center
      of an open-field arena, as conditional cues allowing monkeys to predict the
      location of food rewards hidden in one of two sets of three distinct locations.
      Monkeys were tested in two different conditions: (1) when local visual cues
      marked the two sets of potentially baited locations, so that monkeys could use
      both local and spatial information to discriminate these locations from never
      baited locations; and (2) when no local visual cues marked the two sets of
      potentially baited locations, so that monkeys had to rely on a spatial relational
      representation of the environment to discriminate these locations. No 9-mo-old or
      adult monkey associated the presence of the proximal landmarks, at the center of
      the arena, with the presence of food in one set of three distinct locations. All
      monkeys, however, discriminated the potentially baited locations in the presence
      of local visual cues, thus providing evidence of visual discrimination learning.
      More importantly, all 9-mo-old monkeys tested discriminated the potentially
      baited locations in absence of the local visual cues, thus exhibiting evidence of
      spatial relational learning. These findings indicate that spatial memory
      processes characterized by a relational representation of the environment are
      present as early as 9 mo of age in macaque monkeys.

PMID- 16418442
TI  - Images in cardiovascular medicine. Noninvasive characterization of left atrial
      mass.

PMID- 16418443
TI  - Images in cardiovascular medicine. Architecture of intracoronary thrombi in ST
      elevation acute myocardial infarction: time makes the difference.

PMID- 16418444
TI  - Letter regarding article by Brueckmann et al, "prognostic value of plasma N
      terminal pro-brain natriuretic peptide in patients with severe sepsis".

PMID- 16418445
TI  - Heart services in England.

PMID- 16418446
TI  - Evidence-based medicine: making the grade: miles to go before we sleep.

PMID- 16418447
TI  - Revascularization in systolic heart failure: a difficult decision.

PMID- 16418448
TI  - Brain injury in congenital heart disease.

PMID- 16418449
TI  - Contractile behavior of the left ventricle in diastolic heart failure: with
      emphasis on regional systolic function.

PMID- 16418450
TI  - Mechanisms and use of calcium-sensitizing agents in the failing heart.

PMID- 16418451
TI  - AHA/ACCF Scientific Statement on the evaluation of syncope: from the American
      Heart Association Councils on Clinical Cardiology, Cardiovascular Nursing,
      Cardiovascular Disease in the Young, and Stroke, and the Quality of Care and
      Outcomes Research Interdisciplinary Working Group; and the American College of
      Cardiology Foundation: in collaboration with the Heart Rhythm Society: endorsed
      by the American Autonomic Society.

PMID- 16418452
TI  - The cover. Dorpsstraat.

PMID- 16418454
TI  - Progress in percutaneous heart procedures leads to update in clinical guidelines.

PMID- 16418453
TI  - Post-katrina mental health needs prompt group to compile disaster medicine guide.

PMID- 16418455
TI  - Performance measurements stressed as benchmarks for improving US health care.

PMID- 16418456
TI  - Basal cell and squamous cell carcinoma in persons younger than 40 years.

PMID- 16418457
TI  - Basal cell and squamous cell carcinoma in persons younger than 40 years.

PMID- 16418458
TI  - Basal cell and squamous cell carcinoma in persons younger than 40 years.

PMID- 16418459
TI  - Basal cell and squamous cell carcinoma in persons younger than 40 years.

PMID- 16418460
TI  - Medical student exposure to drug company interactions.

PMID- 16418461
TI  - Characteristics of hospitals performing bariatric surgery.

PMID- 16418462
TI  - Declining incidence of hepatitis A.

PMID- 16418463
TI  - Watchful waiting vs repair of inguinal hernia in minimally symptomatic men: a
      randomized clinical trial.
AB  - CONTEXT: Many men with inguinal hernia have minimal symptoms. Whether deferring
      surgical repair is a safe and acceptable option has not been assessed. OBJECTIVE:
      To compare pain and the physical component score (PCS) of the Short Form-36
      Version 2 survey at 2 years in men with minimally symptomatic inguinal hernias
      treated with watchful waiting or surgical repair. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized trial conducted January 1, 1999, through December 31,
      2004, at 5 North American centers and enrolling 720 men (364 watchful waiting,
      356 surgical repair) followed up for 2 to 4.5 years. INTERVENTIONS: Watchful
      waiting patients were followed up at 6 months and annually and watched for hernia
      symptoms; repair patients received standard open tension-free repair and were
      followed up at 3 and 6 months and annually. MAIN OUTCOME MEASURES: Pain and
      discomfort interfering with usual activities at 2 years and change in PCS from
      baseline to 2 years. Secondary outcomes were complications, patient-reported
      pain, functional status, activity levels, and satisfaction with care. RESULTS:
      Primary intention-to-treat outcomes were similar at 2 years for watchful waiting
      vs surgical repair: pain limiting activities (5.1% vs 2.2%, respectively; P = .06
      [corrected]); PCS (improvement over baseline, 0.29 points vs 0.13 points; P =
      .79). Twenty-three percent of patients assigned to watchful waiting crossed over
      to receive surgical repair (increase in hernia-related pain was the most common
      reason offered); 17% assigned to receive repair crossed over to watchful waiting.
      Self-reported pain in watchful-waiting patients crossing over improved after
      repair. Occurrence of postoperative hernia-related complications was similar in
      patients who received repair as assigned and in watchful-waiting patients who
      crossed over. One watchful-waiting patient (0.3%) experienced acute hernia
      incarceration without strangulation within 2 years; a second had acute
      incarceration with bowel obstruction at 4 years, with a frequency of 1.8/1000
      patient-years inclusive of patients followed up for as long as 4.5 years.
      CONCLUSIONS: Watchful waiting is an acceptable option for men with minimally
      symptomatic inguinal hernias. Delaying surgical repair until symptoms increase is
      safe because acute hernia incarcerations occur rarely.Clinical Trials
      Registration ClinicalTrials.gov Identifier: NCT00263250.

PMID- 16418464
TI  - Thromboembolic adverse events after use of recombinant human coagulation factor
      VIIa.
AB  - CONTEXT: The US Food and Drug Administration (FDA) licensed recombinant human
      coagulation factor VIIa (rFVIIa) on March 25, 1999, for bleeding in patients with
      hemophilia A or B and inhibitors to factors VIII or IX. Use in patients without
      hemophilia has been increasing since licensure. OBJECTIVE: To review serious
      thromboembolic adverse events (AEs) reported to the FDA's Adverse Event Reporting
      System (AERS). DESIGN, SETTING, AND PATIENTS: The AERS database was reviewed from
      March 25, 1999, through December 31, 2004, for thromboembolic AE reports with
      rFVIIa. The AERS database includes US and non-US spontaneous AE reports from both
      approved (specific indications for patients with hemophilia) and unlabeled uses.
      It also includes serious AEs in patients enrolled in postlicensure clinical
      trials who received rFVIIa. Manufacturer reporting to FDA is mandatory, but
      primary notification from clinicians and others to FDA or manufacturers is
      voluntary for spontaneous reports; therefore, AERS underrepresents actual event
      occurrences. MAIN OUTCOME MEASURE: Reported thromboembolic events occurring in
      patients administered rFVIIa. RESULTS: A total of 431 AE reports for rFVIIa were
      found, of which 168 reports described 185 thromboembolic events. Seventeen events
      occurred in patients with hemophilia and 59 occurred in patients enrolled in
      postlicensure trials. Unlabeled indications accounted for 151 of the reports,
      most with active bleeding (n = 115). Reported AEs were thromboembolic
      cerebrovascular accident (n = 39), acute myocardial infarction (n = 34), other
      arterial thromboses (n = 26), pulmonary embolism (n = 32), other venous
      thromboses (including deep vein thrombosis) (n = 42), and clotted devices (n =
      10). In 36 (72%) of 50 reported deaths, the probable cause of death was the
      thromboembolic event. In 144 patients with timing information, 73 events (52%)
      occurred in the first 24 hours after the last dose (30 events within 2 hours).
      Sixty-four reports (38%) noted concomitant use of hemostatic agents. Most reports
      lacked sufficient information to evaluate potential dosage associations.
      CONCLUSIONS: Most reported thromboembolic AEs followed the use of rFVIIa for
      unlabeled indications and occurred in arterial and venous systems, often
      resulting in serious morbidity and mortality. Analysis of the relationship
      between AEs and rFVIIa is hindered by concomitant medications, preexisting
      medical conditions, confounding by indication, and inherent limitations of
      passive surveillance. Randomized controlled trials are needed to establish the
      safety and efficacy of rFVIIa in patients without hemophilia.

PMID- 16418465
TI  - Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.
AB  - CONTEXT: At least 50% of patients with a history of bladder cancer have
      recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but
      can fail to detect some bladder cancers, so a urine test is frequently part of
      the evaluation. OBJECTIVE: To investigate whether a point-of-care proteomic test
      that measures the nuclear matrix protein NMP22 in voided urine could improve
      detection of recurrence during monitoring of patients with a history of bladder
      cancer. DESIGN, SETTING, AND PATIENTS: From September 2001 to February 2002, 23
      academic, private practice, and hospital facilities in 9 US states prospectively
      enrolled 668 consecutive patients with a history of bladder cancer in this cross
      sectional study. Patients provided a voided urine sample for analysis of NMP22
      protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: Diagnosis of
      bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the
      reference standard. The performance of the NMP22 test was compared with voided
      urine cytology as an aid to detection. Testing for the NMP22 tumor marker was
      conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 103
      patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95%
      confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the
      NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P =
      .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during
      initial cystoscopy, including 7 that were high-grade. The sensitivity and
      specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and
      87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only
      3 of the malignancies missed during initial cystoscopy and did not significantly
      increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08).
      CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22
      protein can increase the ability to detect recurrent bladder cancer, with test
      results available during the patient visit.

PMID- 16418466
TI  - Aspirin for the primary prevention of cardiovascular events in women and men: a
      sex-specific meta-analysis of randomized controlled trials.
AB  - CONTEXT: Aspirin therapy reduces the risk of cardiovascular disease in adults who
      are at increased risk. However, it is unclear if women derive the same benefit as
      men. OBJECTIVE: To determine if the benefits and risks of aspirin treatment in
      the primary prevention of cardiovascular disease vary by sex. DATA SOURCES AND
      STUDY SELECTION: MEDLINE and the Cochrane Central Register of Controlled Trials
      databases (1966 to March 2005), bibliographies of retrieved trials, and reports
      presented at major scientific meetings. Eligible studies were prospective,
      randomized controlled trials of aspirin therapy in participants without
      cardiovascular disease that reported data on myocardial infarction (MI), stroke,
      and cardiovascular mortality. Six trials with a total of 95 456 individuals were
      identified; 3 trials included only men, 1 included only women, and 2 included
      both sexes. DATA EXTRACTION: Studies were reviewed to determine the number of
      patients randomized, mean duration of follow-up, and end points (a composite of
      cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular
      mortality], each of these individual components separately, and major bleeding).
      DATA SYNTHESIS: Among 51,342 women, there were 1285 major cardiovascular events:
      625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was
      associated with a significant 12% reduction in cardiovascular events (odds ratio
      [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction
      in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of
      reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There
      was no significant effect on MI or cardiovascular mortality. Among 44,114 men,
      there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776
      cardiovascular deaths. Aspirin therapy was associated with a significant 14%
      reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a
      32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no
      significant effect on stroke or cardiovascular mortality. Aspirin treatment
      increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01)
      and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001). CONCLUSIONS: For women and men,
      aspirin therapy reduced the risk of a composite of cardiovascular events due to
      its effect on reducing the risk of ischemic stroke in women and MI in men.
      Aspirin significantly increased the risk of bleeding to a similar degree among
      women and men.

PMID- 16418467
TI  - Differences in review quality and recommendations for publication between peer
      reviewers suggested by authors or by editors.
AB  - CONTEXT: Many journals give authors who submit papers the opportunity to suggest
      reviewers. Use of these reviewers varies by journal and little is known about the
      quality of the reviews they produce. OBJECTIVE: To compare author- and editor
      suggested reviewers to investigate differences in review quality and
      recommendations for publication. DESIGN, SETTING, AND PARTICIPANTS: Observational
      study of original research papers sent for external review at 10 biomedical
      journals. Editors were instructed to make decisions about their choice of
      reviewers in their usual manner. Journal administrators then requested additional
      reviews from the author's list of suggestions according to a strict protocol.
      MAIN OUTCOME MEASURE: Review quality using the Review Quality Instrument and the
      proportion of reviewers recommending acceptance (including minor revision),
      revision, or rejection. RESULTS: There were 788 reviews for 329 manuscripts.
      Review quality (mean difference in Review Quality Instrument score, -0.05; P =
      .27) did not differ significantly between author- and editor-suggested reviewers.
      The author-suggested reviewers were more likely to recommend acceptance (odds
      ratio, 1.64; 95% confidence interval, 1.02-2.66) or revise (odds ratio, 2.66; 95%
      confidence interval, 1.43-4.97). This difference was larger in the open reviews
      of BMJ than among the blinded reviews of other journals for acceptance (P = .02).
      Where author- and editor-suggested reviewers differed in their recommendations,
      the final editorial decision to accept or reject a study was evenly balanced
      (50.9% of decisions consistent with the preferences of the author-suggested
      reviewers). CONCLUSIONS: Author- and editor-suggested reviewers did not differ in
      the quality of their reviews, but author-suggested reviewers tended to make more
      favorable recommendations for publication. Editors can be confident that
      reviewers suggested by authors will complete adequate reviews of manuscripts, but
      should be cautious about relying on their recommendations for publication.

PMID- 16418468
TI  - A 60-year-old woman who has felt sad for much of her life.

PMID- 16418469
TI  - The 100,000 lives campaign: setting a goal and a deadline for improving health
      care quality.

PMID- 16418470
TI  - The asymptomatic hernia: "if it's not broken, don't fix it".

PMID- 16418477
TI  - JAMA patient page. Depression.

PMID- 16418478
TI  - Unleashing the power of p53: lessons from mice and men.

PMID- 16418479
TI  - Sister chromatid cohesion in silent chromatin: each sister to her own ring.

PMID- 16418480
TI  - Metazoan oocyte and early embryo development program: a progression through
      translation regulatory cascades.

PMID- 16418481
TI  - Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ
      cell survival and spermatogenesis.
AB  - Using a novel tissue-specific RNA interference (RNAi) approach that mimics the
      principle by which naturally occurring microRNAs (miRNA) are made, we demonstrate
      that the Wilms' tumor 1 (WT1) transcription factor has an essential role in
      spermatogenesis. Mice depleted of WT1 in Sertoli nurse cells suffered from
      increased germ cell apoptosis, loss of adherens junctions, disregulation of
      adherence junction-associated genes, and impaired fertility. These effects were
      recapitulated in transgenic mice expressing a dominant-negative form of WT1 in
      Sertoli cells, demonstrating the validity of our RNAi approach. Our results
      indicate that the tumor suppressor WT1 promotes Sertoli cell-germ cell signaling
      events driving spermatogenesis.

PMID- 16418482
TI  - Quantitative microarray profiling provides evidence against widespread coupling
      of alternative splicing with nonsense-mediated mRNA decay to control gene
      expression.
AB  - Sequence-based analyses have predicted that approximately 35% of mammalian
      alternative splicing (AS) events produce premature termination codon (PTC)
      containing splice variants that are targeted by the process of nonsense-mediated
      mRNA decay (NMD). This led to speculation that AS may often regulate gene
      expression by activating NMD. Using AS microarrays, we show that PTC-containing
      splice variants are generally produced at uniformly low levels across diverse
      mammalian cells and tissues, independently of the action of NMD. Our results
      suggest that most PTC-introducing AS events are not under positive selection
      pressure and therefore may not contribute important functional roles.

PMID- 16418483
TI  - Extension of chronological life span in yeast by decreased TOR pathway signaling.
AB  - Chronological life span (CLS) in Saccharomyces cerevisiae, defined as the time
      cells in a stationary phase culture remain viable, has been proposed as a model
      for the aging of post-mitotic tissues in mammals. We developed a high-throughput
      assay to determine CLS for approximately 4800 single-gene deletion strains of
      yeast, and identified long-lived strains carrying mutations in the conserved TOR
      pathway. TOR signaling regulates multiple cellular processes in response to
      nutrients, especially amino acids, raising the possibility that decreased TOR
      signaling mediates life span extension by calorie restriction. In support of this
      possibility, removal of either asparagine or glutamate from the media
      significantly increased stationary phase survival. Pharmacological inhibition of
      TOR signaling by methionine sulfoximine or rapamycin also increased CLS.
      Decreased TOR activity also promoted increased accumulation of storage
      carbohydrates and enhanced stress resistance and nuclear relocalization of the
      stress-related transcription factor Msn2. We propose that up-regulation of a
      highly conserved response to starvation-induced stress is important for life span
      extension by decreased TOR signaling in yeast and higher eukaryotes.

PMID- 16418484
TI  - Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB
      activation.
AB  - CPEB is a sequence-specific RNA-binding protein that controls the polyadenylation
      induced translation of mos and cyclin B1 mRNAs in maturing Xenopus oocytes. CPEB
      activity requires not only the phosphorylation of S174, but also the synthesis of
      a heretofore-unknown upstream effector molecule. We show that the synthesis of
      RINGO/Spy, an atypical activator of cyclin-dependent kinases (cdks), is necessary
      for CPEB-directed polyadenylation. Deletion analysis and mRNA reporter assays
      show that a cis element in the RINGO/Spy 3'UTR is necessary for translational
      repression in immature (G2-arrested) oocytes. The repression is mediated by 3'UTR
      Pumilio-Binding Elements (PBEs), and by its binding protein Pumilio 2 (Pum2).
      Pum2 also interacts with the Xenopus homolog of human Deleted for Azoospermia
      like (DAZL) and the embryonic poly(A)-binding protein (ePAB). Following the
      induction of maturation, Pum2 dissociates not only from RINGO/Spy mRNA, but from
      XDAZL and ePAB as well; as a consequence, RINGO/Spy mRNA is translated. These
      results demonstrate that a reversible Pum2 interaction controls RINGO/Spy mRNA
      translation and, as a result, CPEB-mediated cytoplasmic polyadenylation.

PMID- 16418485
TI  - Unconventional translation of mammalian LINE-1 retrotransposons.
AB  - Long Interspersed Element-1 (LINE-1 or L1) retrotransposons encode proteins
      required for their mobility (ORF1p and ORF2p), yet little is known about how L1
      mRNA is translated. Here, we show that ORF2 translation generally initiates from
      the first in-frame methionine codon of ORF2, and that both ORF1 and the inter-ORF
      spacer are dispensable for ORF2 translation. Remarkably, changing the ORF2 AUG
      codon to any other coding triplet is compatible with retrotransposition. However,
      introducing a premature termination codon in ORF1 or a thermostable hairpin in
      the inter-ORF spacer reduces ORF2p translation or L1 retrotransposition to
      approximately 5% of wild-type levels. Similar data obtained from "natural" and
      codon optimized "synthetic" mouse L1s lead us to propose that ORF2 is translated
      by an unconventional termination/reinitiation mechanism.

PMID- 16418488
TI  - Phosphatidylserine and signal transduction: who needs whom?
AB  - The plasma membrane, long considered a simple barrier between the extracellular
      and intracellular compartments, is now thought to play a pivotal role in many
      physiological processes that regulate the communication of cells with their
      environment. On one hand, the plasma membrane directly participates in
      intracellular signaling; on the other hand, changes in membrane structure
      contribute to the transcellular transfer of biological information. Among the
      membrane constituents, phosphatidylserine is a major actor implicated in these
      effects. Evidence now exists for a role for phosphatidylserine redistribution in
      modulating the activities of several membrane proteins during signaling in
      nonapoptotic T lymphocytes.

PMID- 16418487
TI  - Targeted deletion of a cis-regulatory region reveals differential gene dosage
      requirements for Pdx1 in foregut organ differentiation and pancreas formation.
AB  - Pdx1 (IPF-1 in humans, which is altered in MODY-4) is essential for pancreas
      development and mature beta-cell function. Pdx1 is expressed dynamically within
      the developing foregut, but how its expression characteristics are linked to the
      various steps of organ specification, differentiation, and function is unknown.
      Deletion of a conserved enhancer region (Area I-II-III) from Pdx1 produced a
      hypomorphic allele (Pdx1(DeltaI-II-III)) with altered timing and level of
      expression, which was studied in combination with wild-type and protein-null
      alleles. Lineage labeling in homozygous Area I-II-III deletion mutants
      (Pdx1(DeltaI-II-III/DeltaI-II-III)) revealed lack of ventral pancreatic bud
      specification and early-onset hypoplasia in the dorsal bud. Acinar tissue formed
      in the hypoplastic dorsal bud, but endocrine maturation was greatly impaired.
      While Pdx1(-/-) (protein-null) mice have nonpancreatic abnormalities (e.g.,
      distorted pylorus, absent Brunner's glands), these structures formed normally in
      Pdx1(DeltaI-II-III/DeltaI-II-III) and Pdx1(DeltaI-II-III/-) mice. Surprisingly,
      heterozygous (Pdx1(+/DeltaI-II-III)) mice had abnormal islets and a more severe
      prediabetic condition than Pdx1(+/-) mice. These findings provide in vivo
      evidence of the differential requirements for the level of Pdx1 gene activity in
      the specification and differentiation of the various organs of the posterior
      foregut, as well as in pancreas and gut endocrine cell differentiation.

PMID- 16418486
TI  - A systematic search for downstream mediators of tumor suppressor function of p53
      reveals a major role of BTG2 in suppression of Ras-induced transformation.
AB  - Factors that mediate p53 tumor suppressor activity remain largely unknown. In
      this study we describe a systematic approach to identify downstream mediators of
      tumor suppressor function of p53, consisting of global gene expression profiling,
      focused short hairpin RNA (shRNA) library creation, and functional selection of
      genetic elements cooperating with oncogenic Ras in cell transformation. This
      approach is based on our finding that repression of gene expression is a major
      event, occurring in response to p53 inactivation during transformation and
      immortalization of primary cells. Functional analysis of the subset of genes
      universally down-regulated in the cells that lacked functional p53 revealed BTG2
      as a major downstream effector of p53-dependent proliferation arrest of mouse and
      human fibroblasts transduced with oncogenic Ras. shRNA-mediated knockdown of BTG2
      cooperates with oncogenic Ras to transform primary mouse fibroblasts containing
      wild-type transcriptionally active p53. Repression of BTG2 results in up
      regulation of cyclins D1 and E1 and phosphorylation of Rb and, in cooperation
      with other oncogenic elements, induces neoplastic transformation of primary human
      fibroblasts. BTG2 expression was found to be significantly reduced in a large
      proportion of human kidney and breast carcinomas, suggesting that BTG2 is a tumor
      suppressor that links p53 and Rb pathways in human tumorigenesis.

PMID- 16418489
TI  - Is there clinical value to sentinel lymph node sampling in colon cancer?

PMID- 16418490
TI  - Randomized trial of long-term follow-up for early-stage breast cancer: a
      comparison of family physician versus specialist care.

PMID- 16418491
TI  - Hypoxia response pathways and radiotherapy for head and neck cancer.

PMID- 16418492
TI  - Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3
      21 usage characterize discordance of ZAP-70 and VH mutation status in chronic
      lymphocytic leukemia.
AB  - PURPOSE: Immunoglobulin heavy chain variable-region (VH) gene mutation status and
      zeta-associated protein 70 (ZAP-70) expression are correlated in chronic
      lymphocytic leukemia (CLL), but their concordance is variable. The goal of this
      study was to elucidate additional factors potentially characterizing their
      discordance. PATIENTS AND METHODS: We evaluated ZAP-70 expression by flow
      cytometry, VH status by DNA sequencing, and genomic aberrations by fluorescence
      in situ hybridization in 148 CLL patients. The parameters were analyzed for their
      associations and their individual prognostic impact. RESULTS: ZAP-70 expression
      and VH mutation status were strongly associated in CLL without additional genetic
      high-risk-features as defined by the absence of 11q or 17p deletion and V3-21
      usage (concordance 84%). In contrast, the proportion of discordant cases was
      significantly higher (39%), if such additional genetic high-risk features were
      present. Discordant cases with V3-21 usage were almost exclusively ZAP-70
      positive and VH mutated (89%), whereas all but one of the discordant cases with
      high-risk aberrations were ZAP-70 negative and VH unmutated (92%). By
      multivariate regression analysis, two models were developed, which both include
      high-risk genomic aberrations and, alternatively, VH mutation status and V3-21
      usage or ZAP-70 expression as independent outcome predictors. CONCLUSION: There
      were characteristic modes of discordance between ZAP-70 and VH mutation status
      depending on the presence or absence of additional genetic high-risk features
      such as 11q and 17p deletion or V3-21 usage. Although the biologic background for
      these findings is yet to be determined, these data have biologic and clinical
      implications regarding ZAP-70 as a pathogenic factor and outcome predictor,
      respectively.

PMID- 16418493
TI  - Analysis of micrometastatic disease in sentinel lymph nodes from resectable colon
      cancer: results of Cancer and Leukemia Group B Trial 80001.
AB  - PURPOSE: To determine whether sentinel lymph node (LN) sampling (SLNS) could
      reduce the number of nodes required to characterize micrometastatic disease (MMD)
      in patients with potentially curable colon cancer. PATIENTS AND METHODS: Cancer
      and Leukemia Group B 80001 was a study to determine whether SLNS could identify a
      subset of LNs that predicted the status of the nodal basin for resectable colon
      cancer and, therefore, could be extensively evaluated for the presence of
      micrometastases. Patients enrolled onto this study underwent SLNS after injection
      of 1% isosulfan blue, and both sentinel nodes (SNs) and non-SNs obtained during
      primary tumor resection were sectioned at multiple levels and stained using anti
      carcinoembryonic antigen and anticytokeratin antibodies. RESULTS: Using standard
      histopathology, SNs failed to predict the presence of nodal disease in 13 (54%)
      of 24 node-positive patients. Immunostains were performed for patients whose LNs
      were negative by standard histopathology. Depending on the immunohistochemical
      criteria used to assign LN positivity, SN examination resulted in either an
      unacceptably high false-positive rate (20%) or a low sensitivity for detection of
      MMD (40%). CONCLUSION: By examining both SNs and non-SNs, this multi
      institutional study showed that SNs did not accurately predict the presence of
      either conventionally defined nodal metastases or MMD. As a result, SLNS is not a
      useful technique for the study of MMD in patients with colon cancer.

PMID- 16418494
TI  - BCL2 expression is a prognostic marker for the activated B-cell-like type of
      diffuse large B-cell lymphoma.
AB  - BACKGROUND: The role of BCL2 as a predictor of survival in diffuse large B-cell
      lymphoma (DLBCL) is controversial. DLBCL is heterogeneous, and the expression of
      BCL2 is variable within the two major subgroups of DLBCL, germinal center B-cell
      like (GCB) and activated B-cell-like (ABC) DLBCL, as well as primary mediastinal
      DLBCL. PATIENTS AND METHODS: In this study, we investigated the correlation of
      BCL2 expression with survival in the two major subgroups of DLBCL, as well as the
      mechanisms of BCL2 expression. RESULTS: There was no significant correlation
      between BCL2 protein expression and overall survival within the GCB subgroup, but
      BCL2 expression had a significant adverse effect on overall survival within the
      ABC subgroup (P = .008). This correlation was also observed at the mRNA level (P
      < .04). The difference remained significant when the analyses were performed at
      different cutoff values. The t(14;18) was frequently observed in the GCB subgroup
      and was highly associated with BCL2 expression. Patients with ABC DLBCL did not
      exhibit t(14;18) but had a markedly higher frequency of chromosome 18q21
      amplification, on which BCL2 resides. Thus, alternative mechanisms such as 18q21
      amplification or activation of the nuclear factor-kappa B pathway, as reported
      previously, seem to be mainly responsible for the upregulation of BCL2 expression
      in the ABC subgroup. CONCLUSION: Treating all DLBCL as a single entity ignores
      the mechanistic differences in BCL2 upregulation and obscures the prognostic
      significance of BCL2 expression. Hence, the significance of BCL2 and other
      biomarkers should be assessed in the context of DLBCL subgroups in future
      studies.

PMID- 16418495
TI  - Phase I/II trial assessing bortezomib and melphalan combination therapy for the
      treatment of patients with relapsed or refractory multiple myeloma.
AB  - PURPOSE: Bortezomib has shown synergy with melphalan in preclinical models. We
      assessed the safety, tolerability, and response rate in a dose-escalation study
      of this combination for relapsed or refractory multiple myeloma patients.
      METHODS: Bortezomib was administered from 0.7 to 1.0 mg/m(2) on days 1, 4, 8, and
      11 of a 28-day cycle for up to eight cycles. Oral melphalan was administered in
      escalating doses from 0.025 to 0.25 mg/kg on days 1 to 4. RESULTS: Thirty-five
      patients with relapsed or refractory myeloma were enrolled, 34 of whom were
      assessable for response. Dose-limiting toxicity of grade 4 neutropenia in two of
      six patients in the highest dose cohort led to the assignment of bortezomib 1.0
      mg/m2 and melphalan 0.10 mg/kg as the maximum-tolerated dose (MTD). Responses
      (minimal [MR], partial [PR], or complete [CR]) occurred in 23 of 34 patients
      (68%), including two CRs (6%), three immunofixation-positive CRs (9%), 11 PRs
      (32%), and seven MRs (21%). Responses were observed in five of six assessable
      patients (83%) at the MTD. Median progression-free survival for all patients was
      8 months (range, 2 to 18 months). Grade > or = 3 toxicities were related mostly
      to myelosuppression. Among the 15 patients with grade 1/2 neuropathy at baseline,
      it resolved during treatment in one, worsened in four, and remained stable in 10
      patients. Eight other patients developed grade 1/2 neuropathy during the study.
      CONCLUSION: Bortezomib plus melphalan given on a 28-day schedule showed
      encouraging activity with manageable toxicity and represents a promising
      treatment for myeloma patients.

PMID- 16418496
TI  - Randomized trial of long-term follow-up for early-stage breast cancer: a
      comparison of family physician versus specialist care.
AB  - PURPOSE: Most women with breast cancer are diagnosed at an early stage and more
      than 80% will be long-term survivors. Routine follow-up marks the transition from
      intensive treatment to survivorship. It is usual practice for routine follow-up
      to take place in specialist clinics. This study tested the hypothesis that follow
      up by the patient's family physician is a safe and acceptable alternative to
      specialist follow-up. PATIENTS AND METHODS: A multicenter, randomized, controlled
      trial was conducted involving 968 patients with early-stage breast cancer who had
      completed adjuvant treatment, were disease free, and were between 9 and 15 months
      after diagnosis. Patients may have continued receiving adjuvant hormonal therapy.
      Patients were randomly allocated to follow-up in the cancer center according to
      usual practice (CC group) or follow-up from their own family physician (FP
      group). The primary outcome was the rate of recurrence-related serious clinical
      events (SCEs). The secondary outcome was health-related quality of life (HRQL).
      RESULTS: In the FP group, there were 54 recurrences (11.2%) and 29 deaths (6.0%).
      In the CC group, there were 64 recurrences (13.2%) and 30 deaths (6.2%). In the
      FP group, 17 patients (3.5%) compared with 18 patients (3.7%) in the CC group
      experienced an SCE (0.19% difference; 95% CI, -2.26% to 2.65%). No statistically
      significant differences (P < .05) were detected between groups on any of the HRQL
      questionnaires. CONCLUSION: Breast cancer patients can be offered follow-up by
      their family physician without concern that important recurrence-related SCEs
      will occur more frequently or that HRQL will be negatively affected.

PMID- 16418497
TI  - Endogenous markers of two separate hypoxia response pathways (hypoxia inducible
      factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure
      in head and neck cancer patients recruited in the CHART randomized trial.
AB  - PURPOSE: Randomized controlled trials have generally shown a benefit from
      accelerated radiotherapy in head and neck squamous cell carcinoma (HNSCC).
      However, the large randomized United Kingdom trial CHART (Continuous
      Hyperfractionated Accelerated Radiotherapy) failed to show a benefit of strongly
      accelerated over standard radiotherapy (RT) in 918 patients with HNSCC. In this
      study, we investigated the impact of tumor hypoxia on the outcome of HNSCC
      patients in the CHART trial. There are two distinct hypoxia inducible factors
      (HIFs) that control different gene response pathways and we assessed them both
      with endogenous markers of hypoxia, hypoxia inducible factor HIF-2 alpha (HIF-2)
      and carbonic anhydrase CA9, an indicator of HIF-1 alpha (HIF-1) function.
      METHODS: Tissue from pre-RT biopsies performed in 198 of 918 patients recruited
      was analyzed for the immunohistochemical expression of HIF-2 and CA9. RESULTS: A
      significant association of high HIF2 and of high CA9 reactivity with poor
      locoregional control (P < .0001 and P = .0002, respectively) and poor survival (P
      = .0004 and 0.002, respectively) was noted. In multivariate analysis, HIF-2 and
      CA9 maintained their independent prognostic significance. Coexpression of both
      pathways had an additive effect, supporting their independent role. The uni
      directional hypothesis, that a benefit from randomization to CHART should be seen
      in the nonhypoxic tumors, was supported by the data (one-tailed P = .04).
      CONCLUSION: Expression of endogenous markers of hypoxia for the HIF-1 and HIF-2
      pathway is strongly associated with radiotherapy failure. Using
      immunohistochemical methods it is possible to identify subgroups of HNSCC
      patients who are highly curable with radiotherapy, or who are excellent
      candidates for clinical trials on hypoxia-targeting drugs in two distinct
      pathways.

PMID- 16418498
TI  - Prognostic biomarkers in diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's
      lymphoma. Although it represents a curable disease, less than half of the
      patients are cured with conventional chemotherapy. The highly variable outcome
      reflects a heterogeneous group of tumors, with different genetic abnormalities
      and response to therapy. The International Prognostic Index (IPI) is useful in
      predicting the outcome of DLBCL patients. However, patients with identical IPI
      still exhibit marked variability in survival, suggesting the presence of
      significant residual heterogeneity within each IPI category. The discovery of
      specific genetic alterations and the assessment of protein expression led to the
      identification of multiple novel single molecular markers capable of predicting
      the outcome of DLBCL patients independently of clinical variables. The recent
      application of DNA microarrays and tissue array technologies allowed a better
      understanding of the biology of lymphoma and the development of novel diagnostic
      tools capable of improving the current models for outcome prediction. However,
      much confusion exists in the literature regarding the importance of different
      prognostic biomarkers and their applicability in routine practice. This review
      summarizes the recent advances in our understanding of prognostic biomarkers in
      DLBCL and discusses whether this is the right time for biomarkers-guided risk
      adjusted therapy.

PMID- 16418499
TI  - BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid
      leukemia patients with normal cytogenetics: prognostic implications.
AB  - PURPOSE: Evaluate the impact of BAALC (brain and acute leukemia, cytoplasmic), a
      gene whose expression has been associated with adverse outcome in acute myeloid
      leukemia (AML) with normal cytogenetics, and FLT3 internal tandem duplication
      (ITD) mutations as independent prognostic factors in a larger study. PATIENTS AND
      METHODS: BAALC expression was determined by real-time reverse transcriptase
      polymerase chain reaction in pretreatment blood samples of 307 adults <or= 60
      years of age with AML with normal cytogenetics. Patients were dichotomized at
      BAALC's median expression into low and high expressers. The FLT3 ITD mutant:wild
      type ratio was determined by fragment analysis. RESULTS: Compared with low-BAALC
      patients, high-BAALC patients had a higher rate of primary resistant leukemia
      (16% v 6%; P = .006). High BAALC expression was associated with a higher
      cumulative incidence of relapse (CIR; P = .018) and an inferior overall survival
      (OS; 3-year OS, 36% v 54%; P = .001). On multivariable analysis, high BAALC was
      independently predictive of resistant disease (P = .019), and high BAALC as well
      as a high FLT3 mutant:wild-type ratio were confirmed as the only factors
      predicting a high CIR (BAALC, P = .03; FLT3, P = .01) and inferior OS (BAALC, P =
      .001; FLT3, P = .012). CONCLUSION: This study strengthens BAALC expression as one
      of the most important prognostic factors in AML patients with normal
      cytogenetics. BAALC expression and FLT3 mutation status should assist in
      tailoring induction and postremission therapies.

PMID- 16418500
TI  - Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus
      positive patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte
      programs.
AB  - PURPOSE: Epidemiologic studies show an association between hepatitis C virus
      (HCV) and B-cell non-Hodgkin's lymphoma (NHL). Treatment and outcome of patients
      with diffuse large-cell lymphoma (DLCL) and HCV infection are still a matter of
      debate. PATIENTS AND METHODS: We studied the HCV-positive patients with B-cell
      DLCL included in the Groupe d'Etude des Lymphomes de l'Adulte (GELA) programs LNH
      93 and LNH 98. They were compared with the other patients with DLCL included in
      these programs. HCV infection prevalence was 0.5% (26 of 5,586 patients).
      RESULTS: Histologic types of HCV-positive DLCL were more frequently transformed
      from low-grade lymphoma than DLCL in HCV-negative patients (32% v 6%, P = .02).
      This is also supported by more frequent spleen involvement in HCV-positive
      patients (46% v 17%, P < .001). HCV-positive patients had more frequently
      elevated lactate dehydrogenase levels than other patients (77% v 55%, P = .02).
      Outcome of HCV-positive patients was poorer for overall survival (P = .02) but
      not for event-free survival (P = .13). After matching on age and prognosis
      factors, at 2 years of follow-up, the overall survival was 56% (95% CI, 33% to
      76%) among HCV-positive patients, versus 80% (70% to 89%), and the event-free
      survival was 53% (33% to 72%) versus 74% (64% to 84%). The short-term hepatic
      toxicity of chemotherapy was strongly increased among HCV-positive patients.
      After exclusion of the two subjects with chronic hepatitis B virus infection, the
      overall proportion of subjects undergoing hepatic toxicity was 65% (15 of 23
      patients). CONCLUSION: HCV-positive patients with DLCL differ from other patients
      both at presentation and during chemotherapy. Specific protocols evaluating
      antiviral therapy should be designed for these patients.

PMID- 16418501
TI  - Journal of Histochemistry and Cytochemistry editorial policies and ethical
      guidelines.

PMID- 16418503
TI  - Examination of an inverted repeat within the F factor origin of transfer: context
      dependence of F TraI relaxase DNA specificity.
AB  - Prior to conjugative transfer of plasmids, one plasmid strand is cleaved in a
      site- and strand-specific manner by an enzyme called a relaxase or nickase. In F
      and related plasmids, an inverted repeat is located near the plasmid strand
      cleavage site, and others have proposed that the ability of this sequence to form
      a hairpin when in single-stranded form is important for transfer. Substitutions
      were introduced into a cloned F oriT region and their effects on plasmid transfer
      were assessed. For those substitutions that substantially reduced transfer, the
      results generally correlated with effects on in vitro binding of oligonucleotides
      to the F TraI relaxase domain rather than with predicted effects on hairpin
      formation. One substitution shown previously to dramatically reduce both plasmid
      transfer and in vitro binding to a 17-base oligonucleotide had little apparent
      effect on binding to a 30-base oligonucleotide that contained the hairpin region.
      Results from subsequent experiments strongly suggest that the relaxase domain can
      bind to hairpin oligonucleotides in two distinct manners with different sequence
      specificities, and that the protein binds the oligonucleotides at the same or
      overlapping sites.

PMID- 16418502
TI  - Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization contributes to
      efficient telomere replication in vivo.
AB  - In Saccharomyces cerevisiae at least five genes, EST1, EST2, EST3, TLC1 and
      CDC13, are required for telomerase activity in vivo. The telomerase catalytic
      subunit Est2p and telomerase RNA subunit Tlc1 constitute the telomerase core
      enzyme. Est1p and Est3p are the other subunits of telomerase holoenzyme. In order
      to dissect the function of Est3p in telomere replication, we over-expressed and
      purified recombinant wild-type and mutant Est3 proteins. The wild-type protein,
      as well as the K71A, E104A and T115A mutants were able to dimerize in vitro,
      while the Est3p-D49A, -K68A or -D166A mutant showed reduced ability to dimerize.
      Mutations in Est3p that decreased dimerization also appeared to cause telomere
      shortening in vivo. Double point mutation of Est3p-D49A-K68A and single point
      mutation of Est3p-K68A showed similar telomere shortening, suggesting that the
      K68 residue might be more important for telomerase activity. The ectopic co
      expression of K71A or T115A mutant with wild-type Est3p using centromere plasmids
      caused telomere shortening, while co-expression of the D49A, K68A, D86A or F103A
      mutants with wild-type Est3p had no effect on telomere length regulation. These
      data suggested that dimerization is important for Est3p function in vivo.

PMID- 16418504
TI  - Human papillomavirus triage of atypical squamous cells of undetermined
      significance: cost-effective, but at what cost?

PMID- 16418505
TI  - Momentum building for human epigenome project.

PMID- 16418506
TI  - Latest studies hint at survival advantage with aromatase inhibitors in early
      breast cancer.

PMID- 16418507
TI  - Stat bite: Incidence of and mortality from oral cavity and pharynx cancer, 1975
      2002.

PMID- 16418509
TI  - Advertising campaign puts face on prostate cancer.

PMID- 16418508
TI  - Years of research come to fruition with launch of oral cancer prevention trial.

PMID- 16418510
TI  - Recent research highlights importance of trials halted 10 years ago.

PMID- 16418511
TI  - Cost-effectiveness analysis based on the atypical squamous cells of undetermined
      significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).
AB  - BACKGROUND: The ALTS (atypical squamous cells of undetermined significance
      [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study)
      suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA
      testing followed by referral to colposcopy of only those women with oncogenic HPV
      (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial
      neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for
      immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS
      trial to determine whether HPV DNA testing is a cost-effective alternative to
      immediate colposcopy or conservative management with up to three cytology
      examinations. METHODS: Data from the ALTS trial were used in conjunction with
      medical care costs in a short-term decision model. The model compared the
      incremental costs per case of CIN3+ detected as measured by the incremental cost
      effectiveness ratio (ICER) for the following management strategies for women with
      ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up
      to three cytology examinations. RESULTS: The least costly and least sensitive
      strategy was conservative management with one repeat cytology examination using a
      threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to
      colposcopy. Compared with this strategy, triage to colposcopy based on a positive
      HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected.
      Immediate colposcopy and conservative management with up to three repeat cytology
      visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing.
      Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV
      DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive.
      CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of
      ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs
      to be accounted for in future clinical guidelines and policy analyses.

PMID- 16418512
TI  - Incident high-grade squamous intraepithelial lesions in Senegalese women with and
      without human immunodeficiency virus type 1 (HIV-1) and HIV-2.
AB  - BACKGROUND: Women infected with human immunodeficiency virus type 1 (HIV-1) and 
      2 may be at higher risk of developing cervical cancer than uninfected women. We
      assessed the relationships among human papillomavirus (HPV) types and
      persistence, HIV-1 and/or HIV-2 infection, and the development of high-grade
      cervical squamous intraepithelial lesions (HSILs) in a prospective study.
      METHODS: We studied 627 women with and without HIV-1 and/or HIV-2 infection and
      high-risk HPV infection in Senegal, West Africa, who were assessed every 4 months
      for HSIL and HPV DNA over a mean follow-up of 2.2 years. Cox regression modeling
      was used to assess risks associated with development of HSIL. RESULTS: During
      follow-up, 71 (11%) of 627 women developed HSIL as detected by cytology. HIV
      infected women with high-risk HPV types were at greatest risk for development of
      HSIL. In multivariable modeling, infection with oncogenic HPV types--both
      persistent (hazard ratio [HR] = 47.1, 95% confidence interval [CI] = 16.3 to 136)
      and transient (HR = 14.0, 95% CI = 3.7 to 54)--was strongly associated with HSIL
      risk. In univariate analyses, HIV-positive women infected with HIV-2 were less
      likely to develop HSIL (HR = 0.3, 95% CI = 0.1 to 0.9) than HIV-positive women
      infected with HIV-1. HIV-positive women with CD4+ cell counts between 200 and 500
      cells per microliter (HR = 2.2, 95% CI = 0.8 to 6.3) or fewer than 200 cells per
      milliliter (HR = 5.5, 95% CI = 2.0 to 15.2) were at greater risk of HSIL than HIV
      positive women with CD4 counts of more than 500 cells per milliliter. High plasma
      HIV RNA levels were associated with increased HSIL risk (HR for each order of
      magnitude increase in the level of plasma HIV RNA = 1.4, 95% CI = 1.1 to 1.7; P =
      .005). After adjustment for HPV types and persistence, however, HIV type, plasma
      HIV RNA level, and CD4 count were no longer statistically significantly
      associated with increased risk of HSIL. CONCLUSIONS: HIV-1 and HIV-2 are
      associated with increased risk for development of HSIL. This risk appears to be
      associated primarily with increased HPV persistence that may result from
      immunosuppression related to HIV-1 and/or HIV-2 infection.

PMID- 16418513
TI  - Endogenous sex hormones, breast cancer risk, and tamoxifen response: an ancillary
      study in the NSABP Breast Cancer Prevention Trial (P-1).
AB  - BACKGROUND: Prospective studies have shown an association between increased serum
      levels of estradiol and testosterone and breast cancer risk in postmenopausal
      women. Raloxifene has been shown to reduce breast cancer risk more in women with
      high estradiol levels than in those with lower levels. The purpose of this study
      was to determine whether sex hormone levels were associated with breast cancer
      risk and with response to tamoxifen in a high-risk population. METHODS: Using a
      case-cohort design, we studied 135 women with postmenopausal breast cancer and
      275 postmenopausal women without breast cancer who were enrolled in the National
      Surgical Adjuvant Breast and Bowel Project Cancer Prevention Trial (P-1) and who
      had been treated with tamoxifen or placebo for 69 months. We measured estradiol,
      testosterone, and sex hormone-binding globulin by using radioimmunoassay in
      baseline plasma samples. Relative risks (RRs) and 95% confidence intervals (CIs)
      for invasive breast cancer were estimated for each quartile of sex hormone level
      using Cox proportional hazards models. All statistical tests were two-sided.
      RESULTS: Median plasma levels of estradiol, testosterone, and sex hormone-binding
      globulin were similar between the case and cohort groups. The relative risk of
      breast cancer for women in the placebo group was not associated with sex hormone
      levels (risk of estrogen receptor-positive breast cancer in women by quartile of
      estradiol: Q1 [lowest], RR = 1.0; Q2, RR = 1.16, 95% CI = 0.49 to 2.7; Q3, RR =
      1.08, 95% CI = 0.45 to 2.61; and Q4, RR = 1.29, 95% CI = 0.59 to 2.82). The
      reduced risk of invasive breast cancer in tamoxifen-treated women compared with
      placebo-treated women was not associated with sex hormone levels. CONCLUSIONS:
      These data do not support the use of endogenous sex hormone levels to identify
      women who are at particularly high risk of breast cancer and who are most likely
      to benefit from chemoprevention with tamoxifen.

PMID- 16418514
TI  - Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation
      carriers, 1920-2000.
AB  - BACKGROUND: Mutations in the BRCA genes increase the risk of breast cancer. Valid
      estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene
      mutation carriers are needed for genetic counseling. Recent results suggest that
      penetrance has increased in recent birth cohorts. We examined the cumulative
      breast cancer incidence and mortality before age 70 over a diagnosis period of 80
      years in Icelandic women who carried the BRCA2 founder mutation 999del5. METHODS:
      Information on all breast cancers diagnosed in Iceland since 1911 was obtained
      from the Icelandic Cancer Registry. Mutation status was determined by molecular
      analysis of tissue samples for 847 breast cancer probands who were diagnosed from
      1921 through 1985 and selected without knowledge of family history of breast
      cancer. We estimated the cumulative incidence and mortality from breast cancer
      before age 70 years in BRCA2 mutation carriers from the observed risks in first
      degree relatives who were classified according to mutation status of probands and
      followed-up through 2002. Poisson modeling of these risks was also carried out.
      All statistical tests were two-sided. RESULTS: Of the 847 probands, 88 carried
      the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the
      cumulative incidence of breast cancer before age 70 years in mutation carriers
      increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9%
      (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not
      carry the BRCA2 mutation and in the general Icelandic population incidence
      increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%,
      respectively (all increases of approximately fourfold). During the same period,
      the cumulative risk of death from breast cancer before age 70 years for BRCA2
      mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI
      = 10.9% to 55.5%) (P = .08). However, because the probands were breast cancer
      patients and not a random sample from the population, some bias in the estimation
      of time trends in penetrance cannot be ruled out. CONCLUSIONS: The results
      indicate that the penetrance of the Icelandic BRCA2 founder mutation increased
      nearly fourfold in 80 years, whereas the risk of death from breast cancer before
      age 70 years increased only approximately twofold. Changes in penetrance with
      time should be considered when penetrance is estimated.

PMID- 16418515
TI  - Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic
      Cohort.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) appears to play a role in
      prostate development and carcinogenesis. We investigated whether genetic
      variation at the IGF1 locus is associated with prostate cancer risk. METHODS: We
      sequenced IGF1 exons in germline DNA from 95 men with advanced prostate cancer to
      identify missense variants. IGF1 linkage disequilibrium patterns and common
      haplotypes were characterized by genotyping 64 single-nucleotide polymorphisms
      (SNPs) spanning 156 kilobases in 349 control subjects. Associations between IGF1
      haplotypes and genotypes were investigated among 2320 patients with prostate
      cancer and 2290 control subjects from the Multiethnic Cohort. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were estimated by unconditional logistic
      regression to determine the association between prostate cancer and IGF1
      haplotypes and genotypes. We used permutation testing to correct for multiple
      hypothesis testing. All statistical tests were two-sided. RESULTS: No IGF1
      missense variants were observed. We identified four blocks of strong linkage
      disequilibrium and selected a subset of 29 tagging SNPs that could accurately
      predict both the common IGF1 haplotypes and the remaining SNPs. Haplotype
      analysis revealed nominally statistically significant associations with prostate
      cancer risk in each of the four haplotype blocks: haplotype 1B (OR = 1.21, 95% CI
      = 1.04 to 1.40), haplotype 2C (OR = 1.24, 95% CI = 1.06 to 1.44), haplotype 3C
      (OR = 1.25, 95% CI = 1.03 to 1.50), and haplotype 4D (OR = 1.19, 95% CI = 1.02 to
      1.39). Two SNPs--rs7978742 (Ptrend = .002) and rs7965399 (Ptrend = .002)--were
      perfectly correlated (correlation coefficient = 1.0) with one another and also
      associated with prostate cancer risk. These two SNPs were strong proxies for
      haplotypes 1B, 2C, 3C, and 4D and could account for the haplotype findings.
      Permutation testing revealed that a similarly strong result would be observed by
      chance only 5.6% of the time. CONCLUSION: Inherited variation in IGF1 may play a
      role in the risk of prostate cancer.

PMID- 16418516
TI  - Diabetes mellitus and risk of colorectal cancer in the Singapore Chinese Health
      Study.
AB  - The incidence of colorectal cancer is highest in populations that consume an
      energy-dense diet, have low intakes of vegetables and fruit, or lead a sedentary
      lifestyle. These factors may influence colorectal carcinogenesis via insulin
      pathways. We examined whether diabetes mellitus was associated with colorectal
      cancer in Singapore Chinese, whose body type and lifestyle profiles are distinct
      from those of Western populations. Between April 1993 and December 1998, 63,257
      Singapore Chinese men and women aged 45 to 74 years were enrolled in a
      prospective study of diet and cancer. Each subject provided dietary, medical, and
      lifestyle information through an in-person interview. As of December 31, 2002,
      636 incident colorectal cancer cases had been diagnosed. A history of physician
      diagnosed diabetes was statistically significantly associated with colorectal
      cancer risk in both men (relative risk [RR] = 1.5, 95% confidence interval [CI] =
      1.2 to 2.1) and women (RR = 1.4, 95% CI = 1.0 to 1.9). In stratified analyses,
      this association remained statistically significant among the subset of diabetics
      with high total calorie intake and low physical activity levels. Our results
      support the hypothesis that hyperinsulinemia may play a role in colorectal
      carcinogenesis, even in a relatively lean population.

PMID- 16418517
TI  - IGF1 gene polymorphism and risk for hereditary nonpolyposis colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant
      disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Insulin
      like growth factor-I (IGF-I) is involved in colorectal carcinogenesis, and
      elevated plasma IGF-I levels are associated with sporadic colorectal cancer (CRC)
      risk. We investigated the relationship between IGF1 promoter cytosine-adenine
      (CA) dinucleotide-repeat polymorphism length and CRC risk in 121 MMR gene
      mutation carriers using Cox regression and Kaplan-Meier analysis. All statistical
      tests were two-sided. Time to onset for CRC increased for each decrease in CA
      repeat number (median = 19 repeats, range = 12-22 repeats; hazard ratio [HR] =
      1.17, 95% confidence interval [CI] = 1.05 to 1.31; P = .006). Patients carrying a
      CA(< or = 17) repeat allele had a statistically significantly higher CRC risk (HR
      = 2.36; 95% CI = 1.28 to 4.36; P = .006) than all others and were younger at
      onset (44 years versus 56.5 years; P = .023). These findings indicate a
      statistically significant association between shorter IGF1 CA-repeat lengths and
      increased risk for CRC in HNPCC. This is the first report, to our knowledge, to
      show that IGF1 variant genotypes modify risk of a hereditary form of cancer.

PMID- 16418518
TI  - Re: MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a
      Mediterranean population.

PMID- 16418520
TI  - The genus Hafnia: from soup to nuts.
AB  - The genus Hafnia, a member of the family Enterobacteriaceae, consists of gram
      negative bacteria that are occasionally implicated in both intestinal and
      extraintestinal infections in humans. Despite the fact that the genus currently
      contains only a single species (H. alvei), more extensive phylogenetic depth (two
      or more species) is apparent based upon DNA relatedness and 16S rRNA gene
      sequencing studies. Hafnia causes a variety of systemic infections, including
      septicemia and pneumonia; however, its role as a gastrointestinal pathogen is
      controversial. Many of the data supporting a role for hafniae as enteric
      pathogens were incorrectly attributed to this genus rather than to the actual
      pathogen, Escherichia albertii. There are numerous gaps in our understanding of
      this genus, including ecologic habitats and population genetics, disease
      producing role in animals, phenetic and genetic methods useful in distinguishing
      genomospecies within the H. alvei complex, and bona fide pathogenicity factors.

PMID- 16418522
TI  - Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other
      medicinal properties.
AB  - Complementary and alternative medicines such as tea tree (melaleuca) oil have
      become increasingly popular in recent decades. This essential oil has been used
      for almost 100 years in Australia but is now available worldwide both as neat oil
      and as an active component in an array of products. The primary uses of tea tree
      oil have historically capitalized on the antiseptic and anti-inflammatory actions
      of the oil. This review summarizes recent developments in our understanding of
      the antimicrobial and anti-inflammatory activities of the oil and its components,
      as well as clinical efficacy. Specific mechanisms of antimicrobial and anti
      inflammatory action are reviewed, and the toxicity of the oil is briefly
      discussed.

PMID- 16418524
TI  - Molecular mimicry, bystander activation, or viral persistence: infections and
      autoimmune disease.
AB  - Virus infections and autoimmune disease have long been linked. These infections
      often precede the occurrence of inflammation in the target organ. Several
      mechanisms often used to explain the association of autoimmunity and virus
      infection are molecular mimicry, bystander activation (with or without epitope
      spreading), and viral persistence. These mechanisms have been used separately or
      in various combinations to account for the immunopathology observed at the site
      of infection and/or sites of autoimmune disease, such as the brain, heart, and
      pancreas. These mechanisms are discussed in the context of multiple sclerosis,
      myocarditis, and diabetes, three immune-medicated diseases often linked with
      virus infections.

PMID- 16418523
TI  - Diagnosis of hepatitis a virus infection: a molecular approach.
AB  - Current serologic tests provide the foundation for diagnosis of hepatitis A and
      hepatitis A virus (HAV) infection. Recent advances in methods to identify and
      characterize nucleic acid markers of viral infections have provided the
      foundation for the field of molecular epidemiology and increased our knowledge of
      the molecular biology and epidemiology of HAV. Although HAV is primarily shed in
      feces, there is a strong viremic phase during infection which has allowed easy
      access to virus isolates and the use of molecular markers to determine their
      genetic relatedness. Molecular epidemiologic studies have provided new
      information on the types and extent of HAV infection and transmission in the
      United States. In addition, these new diagnostic methods have provided tools for
      the rapid detection of food-borne HAV transmission and identification of the
      potential source of the food contamination.

PMID- 16418521
TI  - Biological basis for syphilis.
AB  - Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum
      subsp. pallidum. Clinical manifestations separate the disease into stages; late
      stages of disease are now uncommon compared to the preantibiotic era. T. pallidum
      has an unusually small genome and lacks genes that encode many metabolic
      functions and classical virulence factors. The organism is extremely sensitive to
      environmental conditions and has not been continuously cultivated in vitro.
      Nonetheless, T. pallidum is highly infectious and survives for decades in the
      untreated host. Early syphilis lesions result from the host's immune response to
      the treponemes. Bacterial clearance and resolution of early lesions results from
      a delayed hypersensitivity response, although some organisms escape to cause
      persistent infection. One factor contributing to T. pallidum's chronicity is the
      paucity of integral outer membrane proteins, rendering intact organisms virtually
      invisible to the immune system. Antigenic variation of TprK, a putative surface
      exposed protein, is likely to contribute to immune evasion. T. pallidum remains
      exquisitely sensitive to penicillin, but macrolide resistance has recently been
      identified in a number of geographic regions. The development of a syphilis
      vaccine, thus far elusive, would have a significant positive impact on global
      health.

PMID- 16418525
TI  - Penicillium marneffei infection and recent advances in the epidemiology and
      molecular biology aspects.
AB  - Penicillium marneffei infection is an important emerging public health problem,
      especially among patients infected with human immunodeficiency virus in the areas
      of endemicity in southeast Asia, India, and China. Within these regions, P.
      marneffei infection is regarded as an AIDS-defining illness, and the severity of
      the disease depends on the immunological status of the infected individual. Early
      diagnosis by serologic and molecular assay-based methods have been developed and
      are proving to be important in diagnosing infection. The occurrence of natural
      reservoirs and the molecular epidemiology of P. marneffei have been studied;
      however, the natural history and mode of transmission of the organism remain
      unclear. Soil exposure, especially during the rainy season, has been suggested to
      be a critical risk factor. Using a highly discriminatory molecular technique,
      multilocus microsatellite typing, to characterize this fungus, several isolates
      from bamboo rats and humans were shown to share identical multilocus genotypes.
      These data suggest either that transmission of P. marneffei may occur from
      rodents to humans or that rodents and humans are coinfected from common
      environmental sources. These putative natural cycles of P. marneffei infection
      need further investigation. Studies on the fungal genetics of P. marneffei have
      been focused on the characterization of genetic determinants that may play
      important roles in asexual development, mycelial-to-yeast phase transition, and
      the expression of antigenic determinants. Molecular studies have identified
      several genes involved in germination, hyphal development, conidiogenesis, and
      yeast cell polarity. A number of functionally important genes, such as the malate
      synthase- and catalase-peroxidase protein-encoding genes, have been identified as
      being upregulated in the yeast phase. Future investigations pertaining to the
      roles of these genes in host-fungus interactions may provide the key knowledge to
      understanding the pathogenicity of P. marneffei.

PMID- 16418526
TI  - Drug resistance in leishmaniasis.
AB  - Leishmaniasis is a complex disease, with visceral and cutaneous manifestations,
      and is caused by over 15 different species of the protozoan parasite genus
      Leishmania. There are significant differences in the sensitivity of these species
      both to the standard drugs, for example, pentavalent antimonials and miltefosine,
      and those on clinical trial, for example, paromomycin. Over 60% of patients with
      visceral leishmaniasis in Bihar State, India, do not respond to treatment with
      pentavalent antimonials. This is now considered to be due to acquired resistance.
      Although this class of drugs has been used for over 60 years for leishmaniasis
      treatment, it is only in the past 2 years that the mechanisms of action and
      resistance have been identified, related to drug metabolism, thiol metabolism,
      and drug efflux. With the introduction of new therapies, including miltefosine in
      2002 and paromomycin in 2005-2006, it is essential that there be a strategy to
      prevent the emergence of resistance to new drugs; combination therapy, monitoring
      of therapy, and improved diagnostics could play an essential role in this
      strategy.

PMID- 16418527
TI  - Microbial adhesion in flow displacement systems.
AB  - Flow displacement systems are superior to many other (static) systems for
      studying microbial adhesion to surfaces because mass transport and prevailing
      shear conditions can be adequately controlled and notoriously ill-defined slight
      rinsing steps to remove so-called "loosely adhering organisms" can be avoided. In
      this review, we present the basic background required to calculate mass transport
      and shear rates in flow displacement systems, focusing on the parallel plate flow
      chamber as an example. Critical features in the design of flow displacement
      systems are discussed, as well as different strategies for data analysis.
      Finally, selected examples of working with flow displacement systems are given
      for diverse biomedical applications.

PMID- 16418530
TI  - CIB1 is an endogenous inhibitor of agonist-induced integrin alphaIIbbeta3
      activation.
AB  - In response to agonist stimulation, the alphaIIbbeta3 integrin on platelets is
      converted to an active conformation that binds fibrinogen and mediates platelet
      aggregation. This process contributes to both normal hemostasis and thrombosis.
      Activation of alphaIIbbeta3 is believed to occur in part via engagement of the
      beta3 cytoplasmic tail with talin; however, the role of the alphaIIb tail and its
      potential binding partners in regulating alphaIIbbeta3 activation is less clear.
      We report that calcium and integrin binding protein 1 (CIB1), which interacts
      directly with the alphaIIb tail, is an endogenous inhibitor of alphaIIbbeta3
      activation; overexpression of CIB1 in megakaryocytes blocks agonist-induced
      alphaIIbbeta3 activation, whereas reduction of endogenous CIB1 via RNA
      interference enhances activation. CIB1 appears to inhibit integrin activation by
      competing with talin for binding to alphaIIbbeta3, thus providing a model for
      tightly controlled regulation of alphaIIbbeta3 activation.

PMID- 16418531
TI  - Coregulated human globin genes are frequently in spatial proximity when active.
AB  - The organization of genes within the nucleus may influence transcription. We have
      analyzed the nuclear positioning of the coordinately regulated alpha- and beta
      globin genes and show that the gene-dense chromatin surrounding the human alpha
      globin genes is frequently decondensed, independent of transcription. Against
      this background, we show the frequent juxtaposition of active alpha- and beta
      globin genes and of homologous alpha-globin loci that occurs at nuclear speckles
      and correlates with transcription. However, we did not see increased
      colocalization of signals, which would be expected with direct physical
      interaction. The same degree of proximity does not occur between human beta
      globin genes or between murine globin genes, which are more constrained to their
      chromosome territories. Our findings suggest that the distribution of globin
      genes within erythroblast nuclei is the result of a self-organizing process,
      involving transcriptional status, diffusional ability of chromatin, and physical
      interactions with nuclear proteins, rather than a directed form of higher-order
      control.

PMID- 16418533
TI  - Activation-dependent substrate recruitment by the eukaryotic translation
      initiation factor 2 kinase PERK.
AB  - Regulated phosphorylation of the alpha subunit of eukaryotic translation
      initiation factor 2 (eIF2alpha) by the endoplasmic reticulum (ER) stress
      activated protein kinase PERK modulates protein synthesis and couples the
      production of ER client proteins with the organelle's capacity to fold and
      process them. PERK activation by ER stress is known to involve
      transautophosphorylation, which decorates its unusually long kinase insert loop
      with multiple phosphoserine and phosphothreonine residues. We report that PERK
      activation and phosphorylation selectively enhance its affinity for the
      nonphosphorylated eIF2 complex. This switch correlates with a marked change to
      the protease sensitivity pattern, which is indicative of a major conformational
      change in the PERK kinase domain upon activation. Although it is dispensable for
      catalytic activity, PERK's kinase insert loop is required for substrate binding
      and for eIF2alpha phosphorylation in vivo. Our findings suggest a novel mechanism
      for eIF2 recruitment by activated PERK and for unidirectional substrate flow in
      the phosphorylation reaction.

PMID- 16418532
TI  - Telomere tethering at the nuclear periphery is essential for efficient DNA double
      strand break repair in subtelomeric region.
AB  - In the yeast Saccharomyces cerevisiae that lacks lamins, the nuclear pore complex
      (NPC) has been proposed to serve a role in chromatin organization. Here, using
      fluorescence microscopy in living cells, we show that nuclear pore proteins of
      the Nup84 core complex, Nup84p, Nup145Cp, Nup120p, and Nup133p, serve to anchor
      telomere XI-L at the nuclear periphery. The integrity of this complex is shown to
      be required for repression of a URA3 gene inserted in the subtelomeric region of
      this chromosome end. Furthermore, altering the integrity of this complex
      decreases the efficiency of repair of a DNA double-strand break (DSB) only when
      it is generated in the subtelomeric region, even though the repair machinery is
      functional. These effects are specific to the Nup84 complex. Our observations
      thus confirm and extend the role played by the NPC, through the Nup84 complex, in
      the functional organization of chromatin. They also indicate that anchoring of
      telomeres is essential for efficient repair of DSBs occurring therein and is
      important for preserving genome integrity.

PMID- 16418528
TI  - Prospects for vaccine prevention of meningococcal infection.
AB  - Neisseria meningitidis is the leading cause of bacterial meningitis in the United
      States and worldwide. A serogroup A/C/W-135/Y polysaccharide meningococcal
      vaccine has been licensed in the United States since 1981 but has not been used
      universally outside of the military. On 14 January 2005, a polysaccharide
      conjugate vaccine that covers meningococcal serogroups A, C, W-135, and Y was
      licensed in the United States for 11- to 55-year-olds and is now recommended for
      the routine immunization of adolescents and other high-risk groups. This review
      covers the changing epidemiology of meningococcal disease in the United States,
      issues related to vaccine prevention, and recommendations on the use of the new
      vaccine.

PMID- 16418534
TI  - The brain-specific double-stranded RNA-binding protein Staufen2 is required for
      dendritic spine morphogenesis.
AB  - Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein
      family. Its expression is largely restricted to the brain. It is thought to play
      a role in the delivery of RNA to dendrites of polarized neurons. To investigate
      the function of Stau2 in mature neurons, we interfered with Stau2 expression by
      RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant
      reduction in the number of dendritic spines and an increase in filopodia-like
      structures. The number of PSD95-positive synapses and miniature excitatory
      postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin
      effects were caused by overexpression of dominant-negative Stau2. The observed
      phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2
      isoforms. In situ hybridization revealed reduced expression levels of beta-actin
      mRNA and fewer dendritic beta-actin mRNPs in Stau2 down-regulated neurons. Thus,
      our data suggest an important role for Stau2 in the formation and maintenance of
      dendritic spines of hippocampal neurons.

PMID- 16418535
TI  - Coordination between the actin cytoskeleton and membrane deformation by a novel
      membrane tubulation domain of PCH proteins is involved in endocytosis.
AB  - The conserved FER-CIP4 homology (FCH) domain is found in the pombe Cdc15 homology
      (PCH) protein family members, including formin-binding protein 17 (FBP17).
      However, the amino acid sequence homology extends beyond the FCH domain. We have
      termed this region the extended FC (EFC) domain. We found that FBP17 coordinated
      membrane deformation with actin cytoskeleton reorganization during endocytosis.
      The EFC domains of FBP17, CIP4, and other PCH protein family members show weak
      homology to the Bin-amphiphysin-Rvs (BAR) domain. The EFC domains bound strongly
      to phosphatidylserine and phosphatidylinositol 4,5-bisphosphate and deformed the
      plasma membrane and liposomes into narrow tubules. Most PCH proteins possess an
      SH3 domain that is known to bind to dynamin and that recruited and activated
      neural Wiskott-Aldrich syndrome protein (N-WASP) at the plasma membrane. FBP17
      and/or CIP4 contributed to the formation of the protein complex, including N-WASP
      and dynamin-2, in the early stage of endocytosis. Furthermore, knockdown of
      endogenous FBP17 and CIP4 impaired endocytosis. Our data indicate that PCH
      protein family members couple membrane deformation to actin cytoskeleton
      reorganization in various cellular processes.

PMID- 16418538
TI  - OxLDL increases endothelial stiffness, force generation, and network formation.
AB  - This study investigates the effect of oxidatively modified low density
      lipoprotein (OxLDL) on the biomechanical properties of human aortic endothelial
      cells (HAECs). We show that treatment with OxLDL results in a 90% decrease in the
      membrane deformability of HAECs, as determined by micropipette aspiration.
      Furthermore, aortic endothelial cells freshly isolated from hypercholesterolemic
      pigs were significantly stiffer than cells isolated from healthy animals.
      Interestingly, OxLDL had no effect on membrane cholesterol of HAECs but caused
      the disappearance of a lipid raft marker, GM1, from the plasma membrane. Both an
      increase in membrane stiffness and a disappearance of GM1 were also observed in
      cells that were cholesterol-depleted by methyl-beta-cyclodextrin. Additionally,
      OxLDL treatment of HAECs embedded within collagen gels resulted in increased gel
      contraction, indicating an increase in force generation by the cells. This
      increase in force generation correlated with an increased ability of HAECs to
      elongate and form networks in a three-dimensional environment. Increased force
      generation, elongation, and network formation were also observed in cholesterol
      depleted cells. We suggest, therefore, that exposure to OxLDL results in the
      disruption or redistribution of lipid rafts, which in turn induces stiffening of
      the endothelium, an increase in endothelial force generation, and the potential
      for network formation.

PMID- 16418537
TI  - Characterization of nascent HDL particles and microparticles formed by ABCA1
      mediated efflux of cellular lipids to apoA-I.
AB  - The nascent HDL created by ABCA1-mediated efflux of cellular phospholipid (PL)
      and free (unesterified) cholesterol (FC) to apolipoprotein A-I (apoA-I) has not
      been defined. To address this issue, we characterized the lipid particles
      released when J774 mouse macrophages and human skin fibroblasts in which ABCA1 is
      activated are incubated with human apoA-I. In both cases, three types of nascent
      HDL containing two, three, or four molecules of apoA-I per particle are formed.
      With J774 cells, the predominant species have hydrodynamic diameters of
      approximately 9 and 12 nm. These discoidal HDL particles have different FC
      contents and PL compositions, and the presence of acidic PL causes them to
      exhibit alpha-electrophoretic mobility. These results are consistent with ABCA1
      located in more than one membrane microenvironment being responsible for the
      production of the heterogeneous HDL. Activation of ABCA1 also leads to the
      release of apoA-I-free plasma membrane vesicles (microparticles). These larger,
      spherical particles released from J774 cells have the same PL composition as the
      12 nm HDL and contain CD14 and ganglioside, consistent with their origin being
      plasma membrane raft domains. The various HDL particles and microparticles are
      created concurrently, and there is no precursor-product relationship between
      them. Importantly, a large fraction of the cellular FC effluxed from these cells
      by ABCA1 is located in microparticles. Collectively, these results show that the
      products of the apoA-I/ABCA1 interaction include discoidal HDL particles
      containing different numbers of apoA-I molecules. The cellular PLs and
      cholesterol incorporated into these nascent HDL particles originate from
      different cell membrane domains.

PMID- 16418539
TI  - Recent advances in obesity: adiposity signaling and fat metabolism in energy
      homeostasis.
AB  - Interactions between our conserved 'thrifty genotype' and current trends toward
      reduced physical activity and increased food intake are posited as the root cause
      of the rising prevalence of obesity in the modern era. The past decade has seen
      tremendous advances in our understanding of the physiological regulation of
      energy balance and adiposity, and important insights into the pathogenesis of
      obesity. We have gained a more comprehensive view of the energy homeostasis
      system from the discovery of the adiposity hormone leptin, the subsequent
      identification of hypothalamic and other brain neuropeptide systems controlling
      energy balance, and the progress in understanding the molecular mechanisms by
      which cells can sense and respond to changes in metabolic state. Numerous targets
      have been identified for potential pharmacological and genetic approaches to
      obesity management. Some of the most recent developments are prototypic compounds
      that manipulate fat metabolism, both in peripheral tissues and in the brain, to
      reduce body fat synthesis and storage and to increase fat oxidation, to reduce
      food intake, and to increase energy expenditure.

PMID- 16418536
TI  - Structural transitions in the synaptic SNARE complex during Ca2+-triggered
      exocytosis.
AB  - The synaptic SNARE complex is a highly stable four-helix bundle that links the
      vesicle and plasma membranes and plays an essential role in the Ca(2+)-triggered
      release of neurotransmitters and hormones. An understanding has yet to be
      achieved of how this complex assembles and undergoes structural transitions
      during exocytosis. To investigate this question, we have mutated residues within
      the hydrophobic core of the SNARE complex along the entire length of all four
      chains and examined the consequences using amperometry to measure fusion pore
      opening and dilation. Mutations throughout the SNARE complex reduced two distinct
      rate processes before fusion pore opening to different degrees. These results
      suggest that two distinct, fully assembled conformations of the SNARE complex
      drive transitions leading to open fusion pores. In contrast, a smaller number of
      mutations that were scattered through the SNARE complex but were somewhat
      concentrated in the membrane-distal half stabilized open fusion pores. These
      results suggest that a structural transition within a partially disassembled
      complex drives the dilation of open fusion pores. The dependence of these three
      rate processes on position within the SNARE complex does not support vectorial
      SNARE complex zipping during exocytosis.

PMID- 16418540
TI  - Current nutritional treatments of obesity.
AB  - Obesity in our country is a growing concern. There are several different options
      for weight loss; however, individuals must be self-motivated and amendable to
      change in order to achieve success with their weight loss goals. Several
      strategies used by professionals in the US today to treat overweight and obesity,
      include diet therapy, exercise, behavior modification, pharmacotherapy, and
      surgery. The focus of the American Dietetic Association (ADA) Weight Management
      Position Statement is no longer just on weight loss but now on weight management.
      Reaching one's ideal body weight is recommended but not often realistic.
      Frequently, the goal of treatment shifts to maintenance of ones current weight or
      attempts at moderate weight loss. Lifestyle modification or behavioral
      modification interventions rely on analyzing behavior to identify events that are
      associated with appropriate vs. inappropriate eating, exercise, or thinking
      habits. Certain primary strategies that have been found to be useful for helping
      people change their behaviors so that they can lose weight and maintain their
      weight loss, include self-monitoring, stimulus control, cognitive restructuring,
      stress management, social support, physical activity, and relapse prevention.
      Weight loss programs should strive to combine a nutritionally balanced dietary
      regimen with exercise and lifestyle modifications at the lowest possible cost.
      There are several different methods used for dietary modifications; low calorie
      diets, very low calorie diets, fasting, formula diets and meal replacement
      programs, and popular diets. Bariatric surgery is gaining popularity as it has
      been an effective way to treat obesity. Following gastric bypass surgery, the
      patients must be prepared to modify their eating behaviors and dietary selections
      to assist with weight loss and prevent potential complications. Patients should
      be educated on the dietary guidelines extensively prior to surgery and again post
      operatively.

PMID- 16418541
TI  - Pharmacologic treatment of obesity.
AB  - Obesity is strongly associated with conditions such as hypertension, diabetes
      mellitus and osteoarthritis that have known adverse health outcomes. The rising
      prevalence of obesity threatens to overburden our health care system. As a
      result, the need for safe and effective treatment options is urgent.
      Unfortunately, pharmacologic treatment options have been disappointing either
      because of poor side effect profiles or limited long-term efficacy. Our goal is
      to review currently available pharmacologic treatments and the data supporting
      their use so that practicing physicians may better incorporate them into a
      comprehensive, long-term treatment strategy for their patients. We focus on
      orlistat and sibutramine as these are the two medicines approved by the FDA for
      long-term treatment of obesity. In addition, we review briefly agents approved
      for short-term use as well as agents such as zonisamide and topiramate which have
      shown some promise as weight loss agents in specific clinical circumstances.
      Finally, we highlight one medicine currently in phase III clinical trials, an
      endocannabinoid receptor antagonist. Given the overwhelming research focus on
      this disease, it is likely that the coming years will bring more treatment
      options, raising the chance that our patients will have meaningful and sustained
      weight loss.

PMID- 16418529
TI  - Real-time PCR in clinical microbiology: applications for routine laboratory
      testing.
AB  - Real-time PCR has revolutionized the way clinical microbiology laboratories
      diagnose many human microbial infections. This testing method combines PCR
      chemistry with fluorescent probe detection of amplified product in the same
      reaction vessel. In general, both PCR and amplified product detection are
      completed in an hour or less, which is considerably faster than conventional PCR
      detection methods. Real-time PCR assays provide sensitivity and specificity
      equivalent to that of conventional PCR combined with Southern blot analysis, and
      since amplification and detection steps are performed in the same closed vessel,
      the risk of releasing amplified nucleic acids into the environment is negligible.
      The combination of excellent sensitivity and specificity, low contamination risk,
      and speed has made real-time PCR technology an appealing alternative to culture-
      or immunoassay-based testing methods for diagnosing many infectious diseases.
      This review focuses on the application of real-time PCR in the clinical
      microbiology laboratory.

PMID- 16418543
TI  - Body contouring following massive weight loss resulting from bariatric surgery.
AB  - A sharp increase in bariatric surgery has resulted in spike in the population of
      patients seeking body-contouring procedures. Skin and soft tissue redundancy of
      the trunk, buttocks, breasts, upper arms, and thighs following massive weight
      loss is unsightly and results in medical problems such as musculoskeletal strain
      from increased tissue weight, intertrigo or functional limitation with walking,
      maintaining adequate hygiene, bowel and bladder habits and sexual activity. These
      elements compound the inherent psychosocial issues related to massive weight
      loss. Using time-tested plastic surgical techniques, several operations have been
      designed and perfected to address the needs of these patients. These include
      breast, thigh and lower body lift, abdominoplasty, face and neck lifts as well as
      brachioplasty or arm lift. Recognizing that there is a qualitative as well as a
      quantitative difference in the type and amount of tissues in postbariatric
      patients these techniques have been suitably refined to optimize outcomes and
      provide safe and durable re-contouring. Consequently, bariatric surgery and the
      subsequent weight loss require an additional 2-3 years commitment towards body
      contouring procedures. Restoring their body image through reshaping procedures is
      an integral part of completing the treatment of post-weight-loss patients.
      Strategic skills in terms of assessment of each patient, careful planning,
      timing, especially for patient safety and technique are fundamental for the
      success of these often complex and extensive procedures.

PMID- 16418542
TI  - Bariatric surgery.
AB  - Bariatric surgery is currently the only effective long-term treatment of morbid
      obesity and its related co-morbidities. Gastric bypass, adjustable gastric
      banding, and duodenal switch with biliopancreatic diversion are the three most
      common operations performed in the United States to induce sustained weight loss.
      Patient selection is important since compliance postoperatively leads to a
      successful outcome in over 80% of patients. Preoperative psychological and
      behavioral problems may lead to maladaptive eating habits postoperatively that
      defeat the purpose of the surgery. To date, we do not have a 100% reliable method
      of profiling patients who will fail to keep weight off for the long term. It is
      therefore important that patients who have preoperative psychological problems
      that may lead to failure to lose or keep weight off after surgery are offered
      postoperative counseling along with group support.

PMID- 16418544
TI  - Psychosocial aspects of obesity.
AB  - Obese patients have many physical limitations and much psychiatric burden to
      overcome. Several studies have shown that the prevalence of psychiatric morbidity
      in the obese is similar to those with normal weight. However, in obese patients
      seeking treatment there is an increased prevalence (40-60%) of psychiatric
      morbidity, most commonly depression. It is difficult to separate the effects of
      depression on obesity and, on the contrary, the neuroendocrine changes associated
      with stress and depression may cause metabolic changes that predispose and
      perpetuate obesity. The stigma associated with obesity causes bullying in school
      as well as childhood psychiatric morbidity. Prejudice is not limited to the
      general public but exists among health professionals too. This chapter discusses
      the treatment of depression in obesity and the psychiatric evaluation of the pre
      bariatric surgery patient. Education of society, starting with schools and
      including healthcare professionals will reduce bias and stigma as well as assist
      this vulnerable group of patients to seek help for their obesity and the many
      problems that come with it. Given that by the year 2025 obesity will be the
      world's number one health problem with the US leading the way, it is very
      important that we pursue preventive measures as well as encourage research for
      treatments of obesity.

PMID- 16418546
TI  - [The effect of a value clarification program on value clarification in juvenile
      delinquents].
AB  - PURPOSE: The purpose of this study was to identify the effects of a value
      clarification program on value clarification in juvenile delinquents. This study
      employed a two-group pre-post test study design. Data was collected from 16
      subjects from Sept. 29 to Dec. 26, 2003 at N middle school in Seoul, Korea. 9
      subjects constituted the control, while the experimental group was composed of 7
      subjects. METHOD: The structured group therapy used in this study was developed
      on the basis of Raths et al. (1978) theory. The subjects participated in 10
      sessions of therapy that lasted 60 minutes. The instruments used were value
      clarification Test (Lee, 1988), and SPSS Window. RESULT: The experimental group
      showed a significant increase in value clarification after their participation in
      the program. CONCLUSION: Based upon the findings it was concluded that a value
      clarification program was effective in improving value clarification in juvenile
      delinquents in the study.

PMID- 16418545
TI  - Cognitive behavior therapy of binge eating disorder.
AB  - Binge eating disorder (BED) is characterized by recurrent episodes of
      uncontrollable eating, even when not hungry, until uncomfortably full, occurring
      at least twice a week for a 6-month period. This is differentiated from bulimia
      nervosa (BN) by the lack of compensatory mechanisms such as purging/laxative
      abuse. There are significantly higher levels of psychiatric symptoms in patients
      with BED as compared to those without BED. Furthermore, depressive symptomatology
      may increase the patient's vulnerability to binge eating as well as to relapse
      after treatment. Grazing is defined as eating small amounts of food continuously.
      BED in the pre-bariatric patient can manifest as 'grazing' about 2 years post
      bariatric surgery. Treatment should be directed at eating behavior, associated
      psychopathology, weight and psychiatric symptoms. Cognitive behavior therapy is
      based on changing the patient's erroneous ways of thinking about themselves, the
      world and how others perceive them. This includes a focus on normalizing food
      intake as well as challenging dysfunctional thinking, identifying feelings, and
      developing non-food coping skills. It increases a sense of control and therefore
      helps the patient adhere to behavior change strategy, as well as improving mood
      and reducing associated psychopathology. Interpersonal therapy is based on the
      relationship between negative mood low self-esteem traumatic life events,
      interpersonal functioning and the patient's eating behavior. The rationale being
      that eating represents maladaptive coping with underlying difficulties. While
      psychotherapy either CBT or IPT leads to decrease in disordered eating behaviors
      and improved psychiatric symptoms, it has little effect on weight hence; its
      benefit is optimal when used in conjunction with bariatric surgery.

PMID- 16418547
TI  - [A comparative study of how subjects' characteristics and nursing service quality
      influence on hospital revisiting intent between patients and nurses].
AB  - PURPOSE: This study was aimed to examine how subjects' characteristics and
      nursing service quality influence hospital revisiting intent, to compare
      perceptions of patients with those of nurses. METHOD: The questionnaire was
      developed and distributed to 300 patients and nurses at six general hospitals in
      a provincial city, Korea. For data analysis, the SPSS/PC program was used.
      RESULT: The nursing service quality's scores of patients is 3.61, that of nurses
      is 3.77, and there is a significant difference. The hospital revisiting intent's
      score of patients is 4.84, that of nurses is 4.61, and there are no significant
      differences. In subjects' characteristics, patients perceive that the hospital is
      the only different factor, and place hospital revisiting intent at 3.6%. Nurses
      perceive that education level and position are different factors, and place
      hospital revisiting intent at 3.3%. In nursing service quality, patients perceive
      that 2 attributes explain hospital revisiting intent at 17.8% and 2 factors
      explain it at 16.5%; whereas, nurses perceive that 2 attributes explain hospital
      revisiting intent at 15.3% and 3 factors explain it at 12.2%. CONCLUSION: There
      are perception gaps between consumers and providers. So nursing and hospital
      managers must recognize these facts and provide various marketing strategies to
      overcome them.

PMID- 16418548
TI  - [The effects of foot reflexology on fatigue and insomnia in patients suffering
      from coal workers' pneumoconiosis].
AB  - PURPOSE: The purpose of this study was to determine the effects of foot
      reflexology on fatigue and insomnia in patients suffering from coal workers'
      pneumoconiosis. METHOD: This study was a quasi-experimental study of pre-test and
      post-test design in a non-equivalent control group. The subjects of this study
      consisted of both the experimental group of twenty-nine and the control group of
      thirty coal workers' pneumoconiosis patients. Data was collected from December
      10, 2002 to February 15, 2003. Foot reflexology was performed for 60 minutes
      twice a week through five weeks in the experimental group, but none in the
      control group. To evaluate the effects of foot reflexology, the scores of fatigue
      and insomnia were measured before and after the experiment in both groups.
      Fatigue was evaluated by Fatigue Symptoms Inventory. Insomnia was measured with
      the visual analogue scale (VAS). Data of this experiment was analyzed by Chi
      square test, t-test, unpaired t-test and Repeated Measures ANOVA with the SAS
      Program. RESULTS: The scores of fatigue and insomnia decreased in the
      experimental group but not in the control group. There was a significant
      difference of fatigue and insomnia between the two groups. CONCLUSION: It is
      suggested that foot reflexology might have beneficial effects on reducing fatigue
      and insomnia in patients suffering from coal workers' pneumoconiosis, and can be
      recommended as a nursing intervention program for patients with coal workers'
      pneumoconiosis.

PMID- 16418549
TI  - [Working conditions in home health care nursing: a survey of home care nurses in
      hospitals in Korea].
AB  - PURPOSE: The purpose of this research was to address the working conditions of
      home health nurses through a nationwide home health agency survey conducted at
      hospitals. METHOD: The mail surveys were sent to 303 home health nurses nation
      wide and returned with a response rate of 71.8%. RESULT: (a) Seventy-five percent
      of home health agencies were established within the past 5 years and half of home
      health nurses are over 40 years old. (b) Working conditions were considered as
      follows: Seventy-one percent of respondents were full-time employees, sixty-six
      percent of home health nurses had unscheduled visits on a regular day of duty and
      forty-eight percent were on vacation. Fifty-one percent of home health nurses
      have experienced traffic accidents and paid penalties (65.9%). Self-reported
      monthly income level per year was an average of 28,364,000 won. (c) Rates were
      significantly higher for shoulder pain (61.5%), lower back pain (54.1%), knee
      pain (39.4%), and gastrointestinal problems (33.0%). CONCLUSION: These baseline
      results show the importance of improving home health nursing working conditions,
      a comprehensive prevention system and safeguards from physical discomfort.

PMID- 16418550
TI  - [Development of clinical performance indicators for establishing a connecting
      system between hospital performance management and quality improvement].
AB  - PURPOSE: This study aimed at developing integrated clinical performance
      indicators(CPIs) through the analysis of quality improvement(QI) activities of a
      hospital and literature review about performance measures. METHOD: The CPIs were
      developed through the following three stages; 1)Identifying preliminary CPIs 2)A
      staff validity test in preliminary CPIs 3)Developing final CPIs. RESULT: One
      hundred twenty-three preliminary CPIs were developed through QI activities of the
      target hospital for 8 years and literature review. The results of the validity
      test for the preliminary CPIs supported ninety-one items. Sixty-two CPIs were
      selected through integration, reclassification and renaming. Then, eighteen items
      were deleted on account of an imprecise calculation method. Finally, forty-four
      CPIs were confirmed. They consisted of twenty-six items at the hospital level and
      eighteen items at the department level. CONCLUSION: CPIs can be used as criteria
      to evaluate the performance of healthcare organizations, and to decide the
      quality of healthcare for customers. This study may contribute to establishing an
      integrated system between QI activities and performance measurement of healthcare
      organizations.

PMID- 16418551
TI  - [Effects of a exercise program on body composition, physical fitness and lipid
      metabolism for middle-aged obese women].
AB  - PURPOSE: This study was to examine the effects of an exercise program for middle
      aged obese women. METHOD: The exercise program combined folk dance and resistance
      training. The subjects group consisted of 85 middle-aged obese women between 40
      and 60 years of age. Three 8 week sessions consisted of a 55-80% maximum heart
      rate (MHR) exercise for 60-90 minutes a day and 3 times a week from March to
      November, 2004. Data was collected through a pre- and post-exercise test before
      and after each session. Data was collected with Inbody, dynamometer and blood.
      This data was analyzed by descriptive statistics, and a paired t-test with an
      SPSS/PC (10.0 version) program. RESULTS: There were significant positive changes
      in body weight, body fat mass, body mass index, percent body fat, muscle
      strength, muscle endurance, flexibility, and balance quality, but no significant
      positive changes in skeletal mass, fat free mass, percent abdominal fat (waist
      hip ratio), visceral fat area, agility, total cholesterol, high density
      lipoprotein cholesterol, or triglycerides. CONCLUSION: This study showed that an
      exercise program has partially positive effects for middle-aged obese women. The
      results of this study show that exercise at community health centers should
      continue for middle-aged obese women's health.

PMID- 16418552
TI  - [The effect of an internet community on knowledge, self-efficacy and self care
      behavior in workers with hypertension].
AB  - PURPOSE: This study was aimed to evaluate the effect of an internet community on
      knowledge, self-efficacy, and self-care behavior in workers with hypertension.
      METHOD: The research design used was a nonequivalent control group pre-test and
      post-test design. Sixty hypertensive workers participated in this study (Exp.=29,
      Cont.=31). The data was collected from the 3rd of November 2003 to the 27th of
      February 2004 using an interview with questionnaires. Information related to
      hypertension was provided on the internet community weekly and an e-mail
      newsletter was sent in order to increase participation in the internet community.
      We used a tool developed by Park Young-Im (1994) that measured knowledge related
      to hypertension and self-efficacy. A tool developed by Jung Mi-Young (2001) was
      used for self-care behavior. The collected data was analyzed with an chi2-test
      and t-test using the SPSS WIN 10.0 program. RESULT: The internet community helped
      workers with hypertension to increase their knowledge related to hypertension, as
      well as increasing their self-efficacy and self-care behavior. CONCLUSION: An
      internet community could be applied as hypertensive nursing intervention.

PMID- 16418553
TI  - [The effects of a Korean traditional dance movement program in elderly women].
AB  - PURPOSE: This study was aimed to identify the effects of a 12 week Korean
      traditional dance movement program on balance, depression, medical cost, medical
      institution's utilization and fall among elderly women. METHODS: Using a quasi
      experimental design, the experimental group was composed of 130 subjects and the
      control group was composed of 123 subjects. The experimental group participated
      in a 12 week Korean traditional dance movement program 3 times a week from
      December 2002 to February 2003. Data was analyzed with descriptive statistics,
      the chi-square test, paired t-test and t-test. RESULTS: There was significant
      improvement in balance (right leg p=.000, left leg p=.004), depression (p=.000),
      and the medical institution's utilization (p=.001) and fall (p=.002) in the
      experimental group compared to the control group. CONCLUSION: A Korean
      traditional dance movement program improved balance, depression, and decreased
      fall and medical cost in elderly women. Therefore, we recommend this program be
      utilized as a health promoting program and falls preventing program for the
      elderly in the community.

PMID- 16418554
TI  - [Effects of delivery nursing care using essential oils on delivery stress
      response, anxiety during labor, and postpartum status anxiety].
AB  - OBJECTIVES: This study was designed to investigate the effect of delivery nursing
      care using essential oils on labor stress response, labor anxiety and postpartum
      status anxiety for primipara. METHODS: This study used nonequivalent control
      group pretest-posttest design. The subjects of this experiment consisted of forty
      eight primipara with single gestation, full term, & uncomplicated pregnancies.
      Twenty four primipra were in the experimental and control group each. Their mean
      age was 27.9 years old, their mean gestation period 279.9 days. As a treatment,
      delivery nursing care using essential oils was applied by nurses. Data collected
      epinephrine, norepinephrine, anxiety during labor. In the 24 hours after birth,
      the data for the postpartum mother's status anxiety was collected. Data was
      analyzed by t-test, repeated measures ANOVA, Mann-Whitney U test, & Wilcoxon
      signed ranks test with SPSS Program. RESULTS: Plasma epinephrine, norepinephrine
      were significantly low in the experimental group (P=0.001, P=0.033,
      respectively). There was no significant difference between the two groups in
      anxiety during labor and postpartum mother's status anxiety. CONCLUSION: These
      findings indicate that delivery nursing care using essential oils could be
      effective in decreasing plasma epinephrine, norepinephrine. But, that could not
      be verified in decreasing mother's anxiety.

PMID- 16418555
TI  - [Predictive factors of aspects of the transtheoretical model on smoking cessation
      in a rural community].
AB  - PURPOSE: This study was done to evaluate the predictive value of aspects of the
      Transtheoretical model (TTM) of behavior change as applied to smoking cessation
      in a rural population. METHOD: A convenience sample was recruited from a public
      health center in a community. A total of 484 participants were recruited,
      including 319 smokers, 116 ex-smokers and 49 non-smokers. A cross-sectional and
      descriptive design was used in this study. Data was analyzed using descriptive
      statistics, frequency statistics, ANOVA and Logistic regression. RESULT: The
      major findings were 1) The participants were assessed at baseline for their
      current Stage of Change resulting in a distribution with 42.1% in
      Precontemplation, 24.1% in Contemplation, 9.7% in Preparation, 6.2% in Active,
      and 17.9% in the Maintenance stage. 2) There were statistically significant
      differences of processes of change, decisional balance and situational temptation
      across the stages of change. 3) The main factors that affect smoking cessation
      were age, number of years smoking, age when began smoking, self-liberation and
      negative/affective situations, which combined explained 33.2% of the smoking
      cessation. CONCLUSION: TTM variables measured prior to a smoking cessation
      program added little predictive value for cessation outcome beyond that explained
      by demographic and smoking history variables.

PMID- 16418556
TI  - [Effects of abdominal breathing training using biofeedback on stress, immune
      response and quality of life in patients with a mastectomy for breast cancer].
AB  - PURPOSE: This study was to determine the effects of abdominal breathing training
      using biofeedback on stress, immune response, and quality of life. METHOD: The
      study design was a nonequivalent control group pretest- posttest, quasi
      experimental design. Twenty-five breast cancer patients who had completed
      adjuvant chemotherapy were enrolled. The experimental group (n=12) was provided
      with abdominal breathing training using biofeedback once a week for 4 weeks.
      State anxiety, cancer physical symptoms, serum cortisol, T cell subsets (T3, T4,
      T8), NK cell and quality of life were measured both before and after the
      intervention. RESULT: Though state anxiety, cancer physical symptoms, and serum
      cortisol were reduced after 4 weeks of abdominal breathing training using
      biofeedback, there was no statistical significance. It showed, however,
      improvement in quality of life (p=.02), and T3 (p=.04). CONCLUSION: Abdominal
      breathing training using biofeedback improves quality of life in breast cancer
      patients after a mastectomy. However, the mechanism of this beneficial effect and
      stress response requires further investigation with special consideration in
      subject selection and frequency of measurement. Nurses should consider this
      strategy as a standard nursing intervention for people living with cancer.

PMID- 16418557
TI  - [The effects of a sex education program on knowledge related to sexually
      transmitted diseases and sexual autonomy among university students].
AB  - PURPOSE: The purpose of this study was to evaluate the effects of a sex education
      program, which was based on the Health Belief Model, on knowledge related to
      sexually transmitted diseases and sexual autonomy among university students.
      METHOD: A non-equivalent control group, pretest-posttest design was used. The
      four session program was delivered to 18 students during 4 weeks; the control
      group consisted of 23 students. The theme of the first session was "sex, gender,
      and sexuality: all our concern", "dangerous sex" for the second session, "safe
      sex" for the third session, and "right sex for you and me" for the fourth
      session. RESULT: At follow-up, the knowledge related to sexually transmitted
      diseases and sexual autonomy were significantly greater in the intervention group
      than in the control group. CONCLUSION: A sex education program with several
      sessions within the theoretical frame of HBM was effective to improve knowledge
      related to sexually transmitted diseases and sexual autonomy. The results suggest
      the potential of a systematic sexual education program to teach healthy sex and
      to extend the program for other various populations.

PMID- 16418558
TI  - [The effects of problem solving nursing counseling and intensified walking
      exercise on diabetic self-care, coping strategies, and glycemic control among
      clients with DM Type II].
AB  - PURPOSE: The purpose of the study was to identify the effects of problem solving
      nursing counseling and intensified walking exercise on diabetic self-care, coping
      strategies, and glycemic control among older adults with DM type II. METHOD:
      Ninety nine DM patients who were older than 50 were recruited from DM clinics or
      public health centers and conveniently assigned into three groups: the Polar
      (n=41), counseling (n=30) and control groups (n=28). Participants in both Polar
      and counseling groups attended weekly problem solving nursing counseling for 12
      weeks. Polar heart rate monitors were used in the Polar group to intensify
      walking exercise. Data was collected from November 2003 to August 2004 and
      analyzed by ANOVA or ANCOVA using the SPSS WIN program. RESULT: After a 12 week
      intervention, participants in both the Polar and counseling groups reported
      increased diabetic self care behaviors and decreased blood glucose levels, which
      is significantly different from those in the control group. There were no
      distinctively different program effects between the Polar and counseling groups.
      CONCLUSION: Based on the findings, we concluded that problem solving counseling
      alone could have positive effects on diabetic self care and glycemic controls for
      older adults with DM. Future research is needed to identify long-term effects of
      the program.

PMID- 16418559
TI  - [The effects of abdominal meridian massage on menstrual cramps and dysmenorrhea
      in full-time employed women].
AB  - PURPOSE: This study was designed to examine the effects of abdominal
      meridian(Kyongrak) massage on menstrual cramps and dysmenorrhea. METHOD: Eighty
      five women (of 110 screened) enrolled in this study and were employed full-time
      with more than 6.0 points (in 0-10.0 VAS scale) in menstrual cramps or more than
      20 points on the dysmenorrhea scale (range 13-52). The forty-two participants in
      the experimental group received abdominal meridian massage for 5 minutes per day
      during 6 days from the fifth day before menstruation to the first day of
      menstruation and the forty-three participants in the control group didn't receive
      any treatment. Data were collected from June 1st to August 30th, 2003 and
      analyzed using descriptive statistics, chi2-test, and t-test. RESULT: Menstrual
      cramps and dysmenorrhea of the experimental group were significantly lower after
      abdominal meridian massage than those of the control group (p<.001). CONCLUSION:
      Abdominal meridian(Kyongrak) massage was very effective for relief of menstrual
      cramps and dysmenorrhea. Therefore, we suggest that abdominal Kyongrak massage
      can be a useful nursing intervention for women with menstrual cramps or
      dysmenorrhea.

PMID- 16418560
TI  - [A philosophical inquiry into caring in nursing--based on Ricoeur's narrative
      ethics].
AB  - PURPOSE: This paper was aimed to inquire into Ricoeur's self-hermeneutics and
      narrative ethics, and apply it to personal identity constituting caring and care
      ethics in the practice of nursing. Its purpose is to provide a philosophical
      foundation for caring in nursing. METHOD: According to Ricoeur's narrative
      identity, ontological caring was interpreted as personal identity constituting
      caring. His ethics were described as care ethics, which contributed to preserving
      and promoting the personal dignity of the client, as self in search for the good
      life in the nursing practice. RESULTS: Narrative understanding of the client
      pointed to the ontological role of care in the constitution of personal identity.
      From an ethical aspect of the narrative, respect for personal identity and
      personal dignity of the client was crucial to an ethical caring attitude,
      promoting self-esteem in the nursing practice. CONCLUSION: This paper suggested
      that Ricoeur's ethics could provide a philosophical basis for understanding
      ontological and ethical caring in nursing. This contributed to protection of the
      client from the threat of personal identity, as well as respecting their personal
      dignity.

PMID- 16418561
TI  - [Self-image and social support of adolescents among the Korean-Chinese].
AB  - PURPOSE: This study was designed to identify the degree of self-image and social
      support among Korean-Chinese adolescents and investigate the relationship between
      these variables. METHOD: A total of 621 Korean-Chinese adolescents in five middle
      schools in YanBian, China were recruited from March 1st to the 9th, 2005. Data
      was analysed using descriptive statistics, Pearson correlation coefficient, t
      test, and ANOVA with the SPSS 11.5 program. RESULT: In Korean-Chinese
      adolescents, the total self-image score was statistically different for age,
      parents' education status, parents' job and living with parents. In the 12
      subscales, scores of emotional tone, impulse control, sexuality, social
      functioning, vocational attitudes and self-reliance had significant differences
      between groups regarding gender. The total self-image was in the average range.
      However, areas of mental health and family function were lower than average and
      the scale of idealism was higher than average. The adolescents perceived parent's
      support was higher then friend's support. There was a positive correlation
      between self-image and social support. CONCLUSION: The findings suggest there is
      a need to examine self-image and social support of Korean-Chinese adolescents
      according to their parents' marital status and a need to develop a program to
      help these broken family's adolescents.

PMID- 16418562
TI  - [Factors predicting depression in hemodialysis patients].
AB  - PURPOSE: This study was done to provide fundamental data for developing a
      depression prediction model by discovering main factors that affect depression in
      patients who do maintenance hemodialysis. METHOD: The subjects were 191 patients
      doing maintenance hemodialysis selected from outpatient dialysis clinics at 9
      major general hospitals, The Instrument tools utilized in this study were adapted
      from depression, fatigue, sleep disturbance, stress, adaptation,symptoms, daily
      activities, and role limitation and thoroughly modified to verify reliability and
      validity. The collected data was analyzed with a SPSS-PC 11.0 Window Statistics
      Program for real numbers, percentage, average, standard deviation, and multiple
      regression. RESULTS: The correlation factor for depression was (M=2.54) fatigue
      (M=3.12), sleep disturbance (M=2.82), stress (M=3.04), adaptation (M=2.53), daily
      activities (M=2.24), symptoms (M=2.37), and role limitation (M=2.24). The
      strongest factor that affected depression was explained by symptoms of the
      patients who performed hemodialysis. The analysis of the factors that affected
      depression revealed a 58.4% prediction in symptoms, stress, role limitation, and
      adaptation. CONCLUSION: It has been confirmed that the regression equation model
      (Depression=7.351 + .266*symptoms + .260*stress -.189*adaptation + .057*fatigue)
      of this research may serve as a prediction factor for depression in Hemodialysis
      Patients.

PMID- 16418563
TI  - [Effect of an agreement on means to achieve smoking cessation goals among college
      student smokers].
AB  - PURPOSE: The purpose of this study was to identify the degree of attaining a
      smoking cessation goal when an agreement on means to achieve smoking cessation
      among male college student smokers was established. METHOD: This study was
      planned as a nonequivalent control group non-synchronized design and the sample
      was divided into an agreement group and a comparison group by convenience
      sampling in a college of G city. The data was analysed with SPSS Win10.0 using a
      Likelihood chi2-test, Odds ratio, Paired t-test and ANCOVA. RESULT: The theory
      that the degree of smoking cessation will be higher in the agreement group than
      the Comparison group was rejected (delta = 2.567, p = .055). The theory that
      nicotine dependency will be lower in the agreement group than the comparison
      group was supported (F = 3.965, p = .049); however, the theory that the number of
      cigarettes smoked per day will be lower in the agreement group than the
      comparison group was rejected (F = 1.342, p = .252). CONCLUSION: It has been
      shown that an agreement on means to achieve smoking cessation goals is a key
      factor to success in quitting smoking.

PMID- 16418564
TI  - [The relation of trait anger and anger expression to cardiovascular responses and
      depression in middle-aged Korean women].
AB  - PURPOSE: This study was designed to examine the relation of trait anger and anger
      expression to blood pressure, cholesterol, and depression in middle-aged Korean
      women. METHODS: This descriptive correlational design was conducted using a
      convenient sample taken from the health center of K University Hospital located
      in Kyungki province, Korea. The subjects were 252 women aged 40 to 64 years.
      Spielberger's state trait anger expression inventory--Korean version and Beck's
      depression inventory were used for measuring trait anger, state anger, anger
      expression and depression. Data was analyzed by descriptive statistics, t-test,
      Pearson correlation, two-way ANOVA, and cluster analysis using a pc-SAS program.
      RESULTS: The anger expression types by cluster analysis were Anger out/in type,
      Low anger expression type, and Anger control type. The level of cholesterol and
      depression were significantly higher in women with high anger in and high trait
      anger. In addition, the level of depression was significantly higher in women
      with a high anger temperament. CONCLUSIONS: Trait anger and anger in might be
      related to cholesterol and depression in women. However, this study does not
      reveal the relation between blood pressure and trait anger and anger expression.

PMID- 16418565
TI  - [Comparison of health conservation for elders in assisted living facilities and
      nursing homes].
AB  - PURPOSE: This study was performed to evaluate and compare health conservation and
      its related factors of elders in assisted living facilities or nursing homes.
      METHOD: Data for health conservation was collected from 316 elders in 10
      institutions in Daegu city and Kyungpook province from February 1st to February
      22nd, 2005. Data was collected by a structured questionnaire that included
      general characteristics, general health status, health conservation, functional
      health status (ADL, IADL) and depression (GDS-K) scales. The collected data was
      analyzed by the SPSS (version 11.5) program including descriptive statistics, t
      test, chi2-test, Pearson's correlation and stepwise method regression analysis.
      RESULT: The elders in assisted living facilities revealed lower scores in health
      conservation, ADL and IADL than the elders in nursing homes. Predictable
      variables influencing health conservation of the elders in assisted living
      facilities were depression and MAC (Mid-Arm Circumference) that is equal to .270,
      and the the elders in nursing home were depression, IADL, degree of sleep, and
      TSF (Triceps Skin Fold) that is equal to .409. CONCLUSION: The development of a
      health conservation program and long-term health care service system for elders
      in assisted living facilities are needed than for the elders in nursing homes.

PMID- 16418566
TI  - [Effects of educational program of manual lymph massage on the arm functioning
      and the quality of life in breast cancer patients].
AB  - PURPOSE: The purpose of this study was to determine the effect of EPMLM
      (educational program of manual lymph massage) on the arm functioning and QOL
      (quality of life) in breast cancer patients with lymphedema. METHOD: Subjects in
      the experimental group (n=20) participated in EPMLM for 6 weeks from June to
      July, 2005. The EPMLM consisted of training of lymph massage for 2 weeks and
      encourage and support of self-care using lymph massage for 4 weeks. The arm
      functioning assessed at pre-treatment, 2 weeks, and 6 weeks using Arm functioning
      questionnaire. The QOL assessed at pre-treatment and 6 weeks using SF-36. The
      outcome data of experimental group was compared with control group (n=20). The
      collected data was analyzed by using SPSS 10.0 statistical program. RESULT: The
      arm functioning of experimental group was increased from 2 weeks after (W=.224,
      p=.011) and statistically differenced with control group at 2 weeks (Z=-2.241,
      p=.024) and 6 weeks (Z=-2.453, p=.013). Physical function of QOL domain increased
      in experimental group (Z=-1.162, p=.050), also statistically differenced with
      control group (Z=-2.182, p= .030) at 6 weeks. CONCLUSION: The results suggest
      that the educational program of manual lymph massage can improve arm functioning
      and physical function of QOL domain in breast cancer patients with lymphedema.

PMID- 16418567
TI  - [Pain assessment using CRIES, FLACC and PIPP in high-risk infants].
AB  - PURPOSE: Infants at neonatal intensive care units (NICU) are invariably exposed
      to various procedural and environmental stimuli. The study was performed to
      compare the pain responses in three NICU stimulants and to examine the clinical
      feasibility for NICU infants using CRIES, FLACC and PIPP. METHOD: In a
      correlational study, a total of 94 NICU stimulants including angio-catheter
      insertions, trunk-rubbings and loud noises, was observed for pain responses among
      64 infants using CRIES, FLACC and PIPP. RESULTS: A significant difference was
      identified among the mean scores in CRIES (F(2, 91)=47.847, p=.000), FLACC (F(2,
      91)=41.249, p=.000) and PIPP (F(2, 91)=16.272, p=.000) to three stimulants. In a
      Post-hoc Scheff test, an angio-catheter insertion showed the highest scores in
      CRIES, FLACC and PIPP compared to the other two stimulations. A strong
      correlation was identified between CRIES and FLACC in all three stimulations
      (.817 < r < .945) while inconsistent findings were identified between PIPP and
      CRIES or FLACC. CONCLUSIONS: The results of the study support that CRIES and
      FLACC are reliable and clinically suitable pain measurements for NICU infants.
      Further studies are needed in data collection time-point as well as clinical
      feasibility on PIPP administration to assess pain response in infants, including
      premature infants.

PMID- 16418568
TI  - [Influential variables on intention and action to quit smoking between adolescent
      smokers and adult smokers-based on the transtheoretical model].
AB  - PURPOSE: This study identified and compared influential variables on intention
      and action to quit smoking between adolescent smokers and adult smokers. METHODS:
      For the selection of variables, the transtheoretical theory was used. A survey
      was conducted with 376 adolescent smokers in 4 high schools and 451 adult smokers
      in community settings in South Korea. Discriminant analysis was used for data
      analysis. RESULTS: The variables of adolescent smokers that predicted an
      intention to quit smoking were: smoking temptation, self re-evaluation, counter
      conditioning and stimulus control. The variables that predicted an action to quit
      smoking were: self-efficacy for smoking abstinence, pros for smoking, self
      reevaluation, and self liberation. The variables of adult smokers that predicted
      an intention to quit were: smoking temptation, pros for smoking, cons for
      smoking, self reevaluation. The variables that self liberation and predicted an
      action to quit smoking were: self efficacy for smoking abstinence, smoking
      temptation, and counter conditioning. CONCLUSIONS: Developing stage specific
      smoking intervention methods based on different ways of how individuals make a
      decision to quit smoking within their contexts needs to be done.

PMID- 16418569
TI  - [Coincidence analysis of keywords of the Journal of Korean Academy of Nursing
      with MeSH].
AB  - PURPOSE: We try to disclose how much the keywords of the papers from the Journal
      of the Korean Academy of Nursing coincide with MeSH terminologies and to
      understand the major subjects of the recent nursing research in Korea from
      keywords. METHODS: Keywords of journals were extracted and compared with MeSH
      terms. The frequency of the appearance of each keyword was sorted by a descending
      order. RESULTS: Coincidence rate of 1,235 keywords with MeSH terms was 51.6%. Out
      of them, depression, elderly, stress, self efficacy, quality of life, exercise,
      middle-aged women, and women appeared most frequently in descending order.
      CONCLUSION: Coincidence rate of the keywords with MeSH terms was at an acceptable
      level, however to improve it, the education of submitters and editorial board
      members are required, as well as the copy editor, to take a role in checking
      keywords. To infer the subjects of the research from keywords might well
      represent the recent topics of research work.

PMID- 16418570
TI  - Hitting the target: measuring EGFR response to tyrosine kinase inhibitors.

PMID- 16418571
TI  - Halofuginone inhibits tumor growth in the polyoma middle T antigen mouse via a
      thrombospondin-1 independent mechanism.
AB  - Halofuginone inhibits fibrosis by decreasing type I collagen synthesis and tumor
      growth through an anti-angiogenic mechanism. In vitro data suggested that
      halofuginone inhibits angiogenesis through upregulating thrombospondin-1 (TSP-1)
      expression and by inhibiting cell proliferation. To determine whether
      thrombospondin-1 (TSP-1) is necessary for inhibition of tumor growth and
      angiogenesis by halofuginone, we tested the effect of halofuginone on mammary
      tumor growth in polyoma middle T antigen, TSP-1 null (TSP-1-/-PyT) transgenic
      mice. After 30 days of treatment, we found a significant decrease in tumor weight
      in these mice and the extent of tumor growth inhibition was comparable to that
      found in TSP-1 expressing PyT mice (TSP-1+/+PyT). However, no significant
      difference in tumor weight was observed after 60 days of halofuginone treatment
      between control and treated mice in both genotypes. Interestingly, type I
      collagen level was lower in the halofuginone treated TSP-1+/+PyT tumors at 30
      days, but this was not observed in the TSP-1-/-PyT mice. Levels of type I
      collagen did not correlate with blood vessel number as a decrease in the number
      of vessels was observed in the halofuginone treated tumors from both the TSP
      1+/+PyT and TSP-1-/-PyT mice as compared to control tumors. Because halofuginone
      has been shown to inhibit type I collagen synthesis by inhibiting the TGF-beta
      signaling pathway, we measured Smad 2/3 phosphorylation levels and found that
      halofuginone inhibited Smad 2/3 phosphorylation in cells derived from TSP-1+/+PyT
      tumors. We also found that it inhibited Smad 2/3 phosphorylation in cells treated
      with the TGF-beta activating sequence of TSP-1, TSR2+RFK. Our data demonstrate
      that halofuginone inhibits mammary tumor growth in a transgenic mouse model via a
      TSP-1 independent pathway, by decreasing tumor angiogenesis and by inhibiting TGF
      beta signaling.

PMID- 16418572
TI  - Sichuan pepper extracts block the PAK1/cyclin D1 pathway and the growth of NF1
      deficient cancer xenograft in mice.
AB  - There is increasing evidence that more than 70% of cancers including pancreatic,
      breast and prostate cancers as well as neurofibromatosis (NF) are highly addicted
      to abnormal activation of the Ser/Thr kinase PAK1 for their growth. So far FK228
      is the most potent among the HDAC (histone deacetylase) inhibitors that block the
      activation of both PAK1 and another kinase AKT, downstream of PI-3 kinase.
      However, FK228 is still in clinical trials (phase 2) for a variety of cancers
      (but not for NF as yet), and not available for most cancer/NF patients. Thus, we
      have been exploring an alternative which is already in the market, and therefore
      immediately useful for the treatment of those desperate cancer/NF patients. Here
      we provide the first evidence that extracts of Chinese/ Japanese peppercorns
      (Zanthoxyli Fructus) from the plant Zanthoxylum piperitum called "Hua
      Jiao"/"Sansho", block selectively the key kinase PAK1, leading to the
      downregulation of cyclin D1. Unlike FK228, these extracts do not inhibit AKT
      activation at the concentrations that block either cancer growth or PAK1
      activation. The Chinese pepper extract selectively inhibits the growth of NF1
      deficient malignant peripheral nerve sheath tumor (MPNST) cells, without
      affecting the growth of normal fibroblasts, and suppresses the growth of NF1
      deficient human breast cancer (MDA-MB-231) xenograft in mice. Our data suggest
      that these peppercorn extracts would be potentially useful for the treatment of
      PAK1-dependent NF such as MPNST, in addition to a variety of PAK1-dependent
      cancers including breast cancers.

PMID- 16418573
TI  - Genetic ablation of caveolin-1 in mammary epithelial cells increases milk
      production and hyper-activates STAT5a signaling.
AB  - Caveolin-1 (Cav-1) is the main structural protein of caveolae, plasma membrane
      invaginations that have been implicated in vesicular transport, cholesterol
      homeostasis, and the regulation of signal transduction. Previous in vivo studies
      have established a correlation between Cav-1 expression levels and milk
      production. In the normal mouse mammary gland, Cav-1 levels were shown to be
      downregulated during late pregnancy and lactation, via a Ras-p42/44-MAPK-
      dependent mechanism. Conversely, mammary glands from Cav-1 null-/- mice exhibit
      premature lactation, with augmented development of the lobulo-alveolar
      compartment and hyper-activation of the Jak-2/STAT5a signaling cascade. However,
      it remains unknown whether these phenotypes are cell-autonomous, i.e., intrinsic
      to the alveolar mammary epithelial cells, or whether stromal or adipocyte
      secreted factors contribute. To directly address this issue, we have isolated
      primary mammary epithelial cells from wild-type (WT) and Cav-1 null-/- mammary
      glands. We cultured them either in a 2D model (monolayers of mammary epithelial
      cells) or in a 3D system on exogenous basement membrane (Matrigel; to
      reconstitute the minimal lactating unit, i.e., the mammary acinus). We show here
      that Cav-1 deficient mammary epithelial cells display the ability to
      spontaneously generate milk droplets, and to secrete them into the acinar lumen.
      Interestingly, such milk production occurs in the absence of lactogenic
      stimulation. Our results show that monolayers of Cav-1 null mammary epithelial
      cells are enriched in milk droplets, as judged by both (1) phase contrast
      microscopy and (2) immunofluorescence analysis with an antiserum directed against
      mouse milk proteins. Consistently, Cav-1 deficient mammary acini display
      increased milk production and secretion, as evaluated by Western blot analysis
      and electron microscopic examination. Mechanistically, we show that loss of Cav-1
      in mammary epithelial cells induces the baseline constitutive hyper-activation of
      STAT5a signaling, which normally controls the temporal progression of
      lactogenesis in the mammary gland. The possible implications of our findings for
      understanding mammary tumorigenesis are also discussed.

PMID- 16418574
TI  - Promoter hypermethylation of FANCF plays an important role in the occurrence of
      ovarian cancer through disrupting Fanconi anemia-BRCA pathway.
AB  - OBJECTIVE: Individuals with Fanconi anemia (FA) are predisposed to develop
      ovarian cancer than those without FA, this is largely contributed to promoter
      methylation of the FANCF gene and subsequent disruption of the FA-BRCA pathway.
      In an attempt to understand more molecular genetic bases of ovarian cancer, we
      examined the expression of the FANCF and the status of the promoter methylation
      of the FANCF gene in ovarian cancer. METHODS: Seven ovarian cancer cell lines and
      eighteen ovarian cancer specimens were selected for this study. Both genomic DNA
      and total RNA were extracted from fresh tissues and cell lines. The DNA was
      treated with bisulfite and then analyzed with methylation-specific PCR (MSP) to
      detect FANCF methylation. The expression of FANCF mRNA was detected with Reverse
      transcription-polymerase chain reaction (RT-PCR). Additionally, the proliferation
      of cell lines before and after the treatment with demethylating agent 5-Aza-2'
      deoxycytidine(5-ADC) was examined with 3-(4,5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide(MTT) assay. RESULTS: The expression of FANCF mRNA
      decreased in most ovarian cancers as compared with those in normal ovarian
      tissues. Similarly, the level of FANCF protein decreased in ovarian cancers. The
      decrease of FANCF was due, in part, to FANCF methylation (five of 12 specimens).
      The methylation rates were 27.8% (five of 18 specimens) in primary tumors and
      14.3% (one of seven cell lines) in established ovarian cancer cell lines
      respectively. The treatment of ovarian cancer cells with 5-ADC contributed to the
      following results: the inhibition of DNA promoter methylation, the reactivation
      of FANCF mRNA expression and protein, and the subsequent reduction in the
      proliferation of tumor cells both in vitro and in vivo. CONCLUSIONS: The results
      showed that FANCF methylation regulates the expression of FANCF at both mRNA and
      protein levels. Methylation-induced inactivation of FANCF plays an important role
      in the occurrence of ovarian cancers via disrupting the FA-BRCA pathway.

PMID- 16418575
TI  - A functional interplay between Aurora-A, Plk1 and TPX2 at spindle poles: Plk1
      controls centrosomal localization of Aurora-A and TPX2 spindle association.
AB  - Aurora-A and Plk1 are centrosomal kinases involved in centrosome maturation and
      spindle assembly. The microtubule-binding protein TPX2 interacts with, and
      activates, Aurora-A. Here we have used RNA interference-mediated inactivation to
      investigate whether Aurora-A, Plk1 and TPX2 act independently or are part of one
      signaling cascade in spindle formation in mammalian cells. We have identified
      both specific, and over- lapping, roles of each single regulator in centrosome
      maturation and spindle formation: (1) Aurora-A and TPX2 are required for
      centriole cohesion and spindle bipolarity; (2) TPX2, besides its known role in
      microtubule organization, is also involved in centrosome maturation; (3) finally,
      Plk1 controls the localization of Aurora-A to centrosomes, as well as TPX2
      recruitment to microtubules. Based on these results therefore a hierarchical
      functional relation between Plk1 and the Aurora-A/TPX2 pathway emerges.

PMID- 16418576
TI  - New pathways from PKA to the Cdc2/cyclin B complex in oocytes: Wee1B as a
      potential PKA substrate.
AB  - During the growth of the ovarian follicle, mammalian oocytes are arrested in the
      late G2 phase of meiosis through ill-defined mechanisms until shortly before
      ovulation. The molecular machinery controlling the meiotic, as well as mitotic,
      cell cycle is centered around the regulation of the activity of MPF, a complex
      composed of a catalytic Cdc2 and the cyclin B regulatory subunit. Cdc2 kinase is
      inactive as long as oocytes remain in a germinal vesicle state. Its activation is
      the molecular event that triggers germinal vesicle breakdown and oocyte reentry
      into the cell cycle. Countless studies have indicated that levels of the second
      messenger cAMP in the oocyte play a critical role in maintaining meiotic arrest.
      High cyclic AMP levels in the oocyte maintain protein kinase A (PKA) in an
      active/dissociated state, which in turn leads to the phosphorylation of unknown
      protein substrates. The biochemical steps linking a decrease in cAMP levels and
      MPF activation have been explored only recently. Here we will review the data
      supporting a simple scenario whereby Cdc25 and Wee1 kinase are substrates of the
      PKA in oocytes. As as result of these regulatory loops, the Cdc2/cyclin B complex
      is maintained in an inactive state by the two-way PKA-dependent activation of
      Wee1 and inactivation of Cdc25.

PMID- 16418577
TI  - The paradox of histone deacetylase inhibitor-mediated modulation of cellular
      responses to radiation.
AB  - Given the widespread use of radiotherapy in cancer, there has been a longstanding
      interest in the development of chemical compounds that can modify cellular
      responses to ionizing radiation. Additionally, recent terrorism threats
      suggesting attacks with 'dirty bombs' containing combinations of radioactive
      isotopes with conventional explosives, has increased the interest in compounds
      that can protect from radiation injury. Histone deacetylase inhibitors represent
      a new class of compounds that can modulate the effects of radiation. Research
      with histone deacetylase inhibitors has largely focussed on the consequences of
      their ability to alter gene transcription via histone acetylation and on their
      properties as anti-cancer agents. They have been shown to cause cell cycle and
      growth arrest, differentiation and in certain cases apoptosis in cell cultures
      and in vivo. In addition to their intrinsic anti-cancer properties, numerous
      studies have demonstrated that histone deacetylase inhibitors can modulate
      cellular responses to other toxicity-inducing modalities including ionizing
      radiation. The consensus is that histone deacetylase inhibitors markedly enhance
      the sensitivity of cells to radiation by altering numerous molecular pathways.
      Intriguingly, a report has also shown that histone deacetylase inhibitors can
      reduce radiation induced acute and late skin damage using a well-established
      animal model of cutaneous radiation syndrome. Hence, there is an emerging
      interest in potential use of histone deacetylase inhibitors as radiation
      sensitizers or protectors. This review focuses on the different mechanisms by
      which histone deacetylase inhibitors modify cellular responses to ionizing
      radiation.

PMID- 16418578
TI  - GW bodies, microRNAs and the cell cycle.
AB  - GW bodies (GWBs) are cytoplasmic foci initially identified through the use of an
      autoimmune serum targeting the marker protein, GW182. GWBs were first considered
      as both storage centers for a specific subset of mRNAs and degradation sites for
      mRNAs. Interestingly, they are known to vary in size and number throughout the
      cell cycle and are largest in size and most abundant in number during the late S
      and G2 phases. Recent studies have linked RNA interference to GWBs, in that
      disruption or disassembly of GWBs was demonstrated to impair siRNA and miRNA
      silencing activity. As miRNAs are implicated in the regulation of cell cycle
      progression and cell proliferation, it is very likely that GWBs, the critical
      intracellular structures for miRNA function, may very well be also linked to this
      cellular process.

PMID- 16418579
TI  - Fas ligand promotes tumor immune evasion of colon cancer in vivo.
AB  - The study of the role of Fas ligand (FasL/CD95L) in tumor immune evasion has been
      complicated by the discovery that FasL may trigger cytokine secretion and induce
      inflammation. Antisense suppression of FasL expression by colon tumor cells was
      used to investigate if a reduction in endogenously expressed FasL in tumors
      resulted in reduced tumor development and improved anti-tumor immune challenge in
      vivo. Downregulation of FasL expression had no effect on tumor growth in vitro
      but significantly reduced tumor development in syngeneic immune-competent mice in
      vivo. Tumor size was also significantly decreased. Reduced FasL expression by
      tumor cells was associated with increased lymphocyte infiltration. Moreover,
      constitutively expressed FasL was not pro-inflammatory. This study indicates that
      upregulation of FasL expression by colon tumor cells results in an improved anti
      tumor immune challenge in vivo, providing functional evidence in favor of the
      'Fas counterattack' as a mechanism of tumor immune evasion.

PMID- 16418580
TI  - Is base excision repair a tumor suppressor mechanism?
AB  - The base excision repair pathway is critical for the removal of oxidized and
      methylated bases from the DNA. Much of this DNA damage arises endogenously, as a
      result of oxygen metabolism. Several proteins including DNA glycosylases, the
      APE1 endonuclease, DNA polymerase beta and DNA ligase, act in a highly regulated
      and coordinated manner during base excision repair to excise the base adducts
      from the DNA and restore the normal DNA sequence. Both germline and tumor
      associated variants of genes encoding these proteins have been identified in
      humans. In many cases, the protein variant has been shown to have properties that
      could contribute to the development of cancer, suggesting that base excision
      repair acts as a tumor suppressor mechanism in humans. Limited epidemiological
      studies are consistent with this view. Our review of the literature indicates
      that additional laboratory and epidemiological studies of the role of base
      excision repair in cancer etiology is warranted.

PMID- 16418582
TI  - Clinical trial recruitment and retention of a vulnerable population: HIV patients
      with chronic diarrhea.
AB  - This article describes the recruitment and retention strategies implemented for a
      prospective, randomized, clinical trial conducted at a single study facility. The
      purpose of the study was to examine the effects of a nutritional intervention to
      reduce the episodes of diarrhea in patients with the human immunodeficiency
      virus/acquired immune deficiency syndrome. This article reviews the challenges
      faced by the research team during the conduct of the study and discusses the
      approaches implemented to reduce the barriers to study participation.

PMID- 16418583
TI  - The pathophysiology of chemotherapy-induced nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting is a major debilitating side effect of
      oncology treatment despite recent advances in pharmaceutical management. Nurses
      who provide care to patients experiencing nausea and vomiting are often only
      marginally aware of the pathophysiological processes involved in the treatment. A
      better understanding of the science behind current interventions to reduce nausea
      and vomiting may help nurses use those interventions more effectively. This
      article reviews current knowledge about the pathophysiology of chemotherapy
      induced nausea and vomiting. By understanding the pathophysiology behind this
      patient experience, gastroenterology nurses can develop a better understanding of
      the common symptoms of nausea and vomiting in general. When a nurse understands
      the complexity of factors causing nausea and vomiting, he or she will be better
      able to provide appropriate interventions to reduce these symptoms.

PMID- 16418584
TI  - Gastrostomy tubes: facts, fallacies, fistulas, and false tracts.
AB  - The first successful gastrostomy was performed 130 years ago. Although it is
      difficult to ascertain the exact number of gastrostomy or jejunostomy tubes
      placed annually in the United States, it is estimated approximately 230,000
      gastrostomy procedures were performed in U.S. hospitals in 2001. Of these, 11,000
      were performed in children. Despite the many years gastrostomy tubes have been in
      use, they are not free from complications. The purpose of this article is to
      review the authors' experience with pediatric patients who have undergone
      radiographic placement of gastrostomy or jejunostomy tubes.

PMID- 16418587
TI  - Colon preparation.

PMID- 16418586
TI  - Evaluation of demographic, behavioral, and procedural factors on pain perception
      by patients undergoing colonoscopy and moderate sedation.
AB  - This prospective study collected demographic, behavioral, and procedural factors
      data on the pain perception of 100 patients as they were undergoing colonoscopy
      and moderate sedation. Patients were asked to rate pain on a 4-point categorical
      scale (no, slight, moderate, or severe pain) before the colonoscopy, every 5
      minutes during, and after the colonoscopy. Before discharge, patients recorded
      overall pain control satisfaction on a 100-mm visual analog scale (0=not
      satisfied and 100=satisfied). The average patient age was 54.3 years, and 56%
      were male. A total of 59 subjects reported an averaged "no pain" or "slight pain"
      rating, and 41 reported moderate or severe pain. The median visual analog scale
      score was 92.5, demonstrating a high level of overall pain-control satisfaction.
      Patient reports of pain during the colonoscopy procedure may not be recalled by
      the moderately sedated patient, as evidenced from the high level of satisfaction
      of overall pain control demonstrated by the visual analog scale finding. Compared
      with women and non-Whites, a larger proportion (P<.05) of men and Whites reported
      "no" or "slight pain"; moreover, a larger proportion (P<.05) of patients
      experiencing no preprocedure anxiety reported "no" or "slight pain" compared with
      those experiencing anxiety before their procedure. Compared with other sedation
      groups, a larger proportion (P<.05) of patients receiving Versed + Fentanyl
      reported "no" or "slight pain" during their procedures. Other factors that were
      analyzed, including age, body mass index, history of alcohol consumption,
      smoking, narcotic use, length of procedure, and medical or nursing intervention,
      did not appear to influence the level of pain perceived by patients observed in
      this study.

PMID- 16418588
TI  - Manual cleaning.

PMID- 16418589
TI  - Ethics and endoscopy.

PMID- 16418590
TI  - Wireless capsule endoscopy: two research methods, one outcome.

PMID- 16418593
TI  - Deletion of chromosome 21 disturbs human brain morphogenesis.
AB  - PURPOSE: Humans with small deletions of chromosome 21 provide important models
      for understanding the role of dosage-sensitive genes in brain morphogenesis. To
      identify chromosome 21 genes responsible for defects of the central nervous
      system, we determined the deleted regions and brain malformations in three
      unrelated individuals with overlapping partial deletions of chromosome 21.
      METHODS: Fluorescent in situ hybridization and magnetic resonance imaging were
      used to define the chromosomal structure and structural brain abnormalities
      present in these three individuals. RESULTS: The regions of chromosome 21 found
      to be deleted in these individuals were as follows: case 1: KCNJ6 to the
      telomere; case 2: ITSN1 to the telomere; and case 3: ITSN1 to PCNT2. The
      abnormalities of brain structure shared by all included microcephaly, pachygyria,
      polymicrogyria, colpocephaly, hypoplastic corpus callosum and white matter,
      hypoplastic cerebellum, and enlarged ventricular system. The clinical features in
      common included mental retardation, microcephaly, facial dysmorphism, and
      epilepsy (severe in one patient). CONCLUSION: From analyses of the molecular,
      cytogenetic, and neuroimaging data from these three individuals, combined with
      those from previously reported cases, we infer that deletion of an 8.4-Mb region
      in chromosome band 21q22.2-22.3 (KCNJ6-COL6A2) is associated with cortical
      dysplasia. We propose that one or more dosage-sensitive genes in this region
      contributes to cortical development and that deletion of 21q22.2-22.3 should be
      considered in the diagnosis of mentally retarded patients with facial dysmorphism
      and cerebral dysplasia.

PMID- 16418594
TI  - Characterization of neuronopathic Gaucher disease among ethnic Poles.
AB  - PURPOSE: Gaucher disease is a common lysosomal storage disease that results from
      inherited mutations in the gene (GBA) encoding acid beta-glucosidase (GCase).
      Here, the clinical and molecular findings of the subacute neuronopathic variant
      are delineated among ethnic Poles. METHODS: Longitudinal studies of visceral,
      bony, and central nervous system involvement are delineated clinically. Complete
      gene GBA sequencing was used to characterize the mutations and haplotypes in this
      population. RESULTS: A greater frequency of subacute neuronopathic Gaucher
      disease (type 3) is present among ethnic Poles compared with other European
      countries. Two type 3 phenotypes were found: The first was an early-onset variant
      with massive visceral disease, progressive kyphoscoliosis, mild cognitive
      deficits, and survival for three or more decades. This variant resembles the
      "Norrbottnian" Swedish phenotype. The other variant had more severe progressive
      central nervous system disease, milder visceral involvement, and absence of
      kyphoscoliosis. Myoclonus was present in some patients. Neither variant had bone
      crises and/or pain as major components. The L444P/L444P genotype was most common,
      but on several different haplotype backgrounds. Other alleles encoded D409H,
      V305L, and E326K/A446P on various haplotypes. CONCLUSIONS: These studies provide
      additional expansion of the type 3 genotypes with some commonalities with and
      differences from other reported variants. Also, such phenotypic expansion should
      be expected in the other variants of Gaucher disease as the spectrum of ethnic
      variation becomes more fully delineated.

PMID- 16418595
TI  - Preclinical validation of fluorescence in situ hybridization assays for clinical
      practice.
AB  - PURPOSE: Validation of fluorescence in situ hybridization assays is required
      before using them in clinical practice. Yet, there are few published examples
      that describe the validation process, leading to inconsistent and sometimes
      inadequate validation practices. The purpose of this article is to describe a
      broadly applicable preclinical validation process. METHODS: Validation is
      performed using four consecutive experiments. The Familiarization experiment
      tests probe performance on metaphase cells to measure analytic sensitivity and
      specificity for normal blood specimens. The Pilot Study tests a variety of normal
      and abnormal specimens, using the intended tissue type, to set a preliminary
      normal cutoff and establish the analytic sensitivity. The Clinical Evaluation
      experiment tests these parameters in a series of normal and abnormal specimens to
      simulate clinical practice, establish the normal cutoff and abnormal reference
      ranges, and finalize the standard operating procedure. The Precision experiment
      measures the reproducibility of the new assay over 10 consecutive working days.
      To illustrate documentation and analysis of data with this process, the results
      for a new assay to detect fusion of IGH and BCL3 associated with
      t(14;19)(q32;q13.3) in lymphoproliferative disorders are provided in this report.
      RESULTS: These four experiments determine the analytic sensitivity and
      specificity, normal values, precision, and reportable reference ranges for
      validation of the new test. CONCLUSION: This report describes a method for
      preclinical validation of fluorescence in situ hybridization studies of metaphase
      cells and interphase nuclei using commercial or home brew probes.

PMID- 16418596
TI  - Toward cultural competence in cancer genetic counseling and genetics education:
      lessons learned from Chinese-Australians.
AB  - PURPOSE: In societies such as Australia with a strong multicultural makeup,
      culturally determined attitudes to genetics, testing, and counseling may be
      incompatible with current genetics service provision. METHODS: An ethnographic
      investigation using purposive sampling to increase subject diversity was used to
      explore the range of beliefs about kinship and inheritance using Chinese
      Australians as a case. Participants comprised a sample of 15 Chinese-Australians
      who had been recruited through several community-based organizations. RESULTS:
      The level of acculturation does not correlate with holding beliefs about
      inheritance, kinship, and causes of hereditary cancer that are based on "Western"
      biomedical or traditional concepts. Mismatch between beliefs may exist within
      families that can impact participation in cancer genetic testing. Family history
      taking that underpins the surveillance, management, and referral to genetic
      counseling where there is a strong family history of breast, ovarian, or
      colorectal cancer can also be impacted unless recognition is made of the
      patrilineal concept of kinship prevalent in this Chinese-Australian community.
      CONCLUSION: This community-based study confirmed and validated views and beliefs
      on inheritance and kinship and inherited cancer attributed to senior family
      members by Chinese-Australians who attended cancer genetic counseling. Barriers
      to communication can occur where there may be incompatibility within the family
      between "Western" and traditional beliefs. The findings were used to develop
      strategies for culturally competent cancer genetic counseling with Australian
      Chinese patients. These include nonjudgmental incorporation of their belief
      systems into the genetic counseling process and avoidance of stereotyping. They
      have also influenced the development of genetics education materials to optimize
      family history taking.

PMID- 16418598
TI  - Familial risks of aortic aneurysms among siblings in a nationwide Swedish study.
AB  - PURPOSE: Aortic aneurysms have a high fatality rate that could be reduced with
      control of risk factors and use of available screening methods for detection of
      early changes in aortic walls. The available data on familial risks, a potential
      indication for screening, are mainly limited to abdominal aortic aneurysms.
      METHODS: A nationwide Swedish cohort was constructed by linking the
      Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge
      Register and the Cause of Death Register for data on aortic aneurysms from years
      1987 to 2001. Standardized incidence ratios (SIRs) were calculated for affected
      siblings by comparing with those whose siblings had no aneurysm. RESULTS: A total
      of 71 affected siblings were identified with a familial SIR of 8.71; when one
      sibling was diagnosed before age 50 years, the SIR was 19.69. For concordant
      thoracic or concordant abdominal aneurysms, the SIRs were 21.68 and 13.06,
      respectively. For brothers, the risk of abdominal aneurysms was 14.63, and 49.50
      for diagnosis before age 50 years. Familial risks and the effects of early
      diagnostic age were shared by the anatomic subtypes of aneurysms. Within limits
      of the sample size, no gender differences could be observed. Affected siblings
      constituted 2.2% of all diagnosed patients. CONCLUSIONS: A family history of any
      aortic aneurysms and age groups younger than 50 years should be considered in
      recommendations for screening. The high familial risks are likely to be the
      result of heritable genes, the identification of which would allow gene testing
      and preventive counseling.

PMID- 16418597
TI  - What is in a cause? Exploring the relationship between genetic cause and felt
      stigma.
AB  - PURPOSE: Concern over stigma as a consequence of genetic testing has grown in
      response to the recent increase in genetic research and testing resulting from
      the Human Genome Project. However, whether a genetic or hereditary basis
      necessarily confers a stigma to a condition remains unexamined. METHODS: We
      performed a qualitative interview study with 86 individuals with one of four
      conditions: deafness or hearing loss, breast cancer, sickle cell disease, and
      cystic fibrosis. The first two groups were divided approximately between people
      who ascribed their conditions to a genetic or hereditary cause and those who did
      not. RESULTS: Respondents interpreted genetic or hereditary causes and nongenetic
      causes in a variety of ways. Subjects with breast cancer reported the most
      consistently negative interpretation of genetic cause. This response concerned
      future ill health, not an enduring sense of stigma. Deaf and hard of hearing
      subjects provided the most consistently positive comments about a genetic or
      hereditary basis to their condition, casting familial hearing loss as a vital
      component of group and individual identity. Respondents with sickle cell disease
      and cystic fibrosis offered similar and positive interpretations of the genetic
      cause of their condition insofar as it meant their conditions were not
      contagious. CONCLUSIONS: Although some subjects report feeling stigmatized as a
      result of their condition, this stigmatization is not uniformly associated with
      the condition's cause, genetic or otherwise. Instead, stigma emerges from a
      variety of sources in the context of the lived experience of a particular
      condition.

PMID- 16418599
TI  - The diagnostic utility of a genetics evaluation in children with pervasive
      developmental disorders.
AB  - PURPOSE: A genetics evaluation of children with pervasive developmental disorders
      (PDDs) identifies a diagnosis in 6% to 15% of cases. However, previous studies
      have not measured the incidence of genetic disorders among children with autistic
      like features who do not necessarily meet the Diagnostic and Statistical Manual
      for Mental Disorders, Fourth Edition criteria for PDD. METHODS: We identified 101
      patients at our institution referred for PDD, autism, Asperger syndrome, or
      autistic features. Seventy-eight were males and 23 were females, giving a male-to
      female ratio of 3.4:1. No diagnosis was identified on examination alone, although
      Rett syndrome was suspected in six females. Seventeen patients did not undergo
      any type of testing because of noncompliance. RESULTS: Of the remaining 84
      patients analyzed, seven (8.3%) were found to have abnormalities on testing.
      Three chromosomal anomalies were found: one with 5p duplication, one with low
      level mosaicism for trisomy 21, and one with an unbalanced 10;22 translocation.
      Three females were diagnosed with Rett syndrome after MECP2 analysis identified a
      disease-causing mutation. The remaining patient was found to have an elevated
      urine orotic acid, with a normal ammonia level, of unknown significance.
      CONCLUSION: On the basis of our series, the yield of a genetics evaluation in
      patients with features of PDD who do not necessarily meet the Diagnostic and
      Statistical Manual for Mental Disorders, Fourth Edition criteria is 8.3%.
      Approximately half of these were the result of a chromosomal abnormality. Three
      cases of Rett syndrome were identified for which autistic behaviors are a well
      described feature. These findings suggest that a high-resolution karyotype
      provides the greatest diagnostic yield for patients with autistic-like features.
      MECP2 analysis should be considered for females who present with autistic
      behaviors.

PMID- 16418600
TI  - Genetic investigation of the TSPYL1 gene in sudden infant death syndrome.
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) constitutes the most frequent
      cause of death in the postperinatal period in Germany. Recently, a lethal
      phenotype characterized by sudden infant death with dysgenesis of the testes
      syndrome (SIDDT) was identified to be caused by loss of function mutations in the
      TSPYL1 gene. PURPOSE: The study's purpose was to reveal a possible role of TSPYL1
      in SIDS. METHODS: DNA samples of 126 SIDS cases and 261 controls were
      investigated. RESULTS: We found five sequence variations, each of them causing an
      amino acid substitution. No Hardy Weinberg disequilibrium and no significant
      difference in allele frequencies between patients and controls were observed for
      any variation. In one female patient a p.F366L amino acid polymorphism was found
      heterozygous, which could not be displayed in controls. A pathogenic implication
      of this substitution, which is conserved in primates and rodents, cannot be ruled
      out completely. Because SIDDT is the result of homozygous TSPYL1 mutations, this
      heterozygous exchange cannot solely explain the sudden death in this child. The
      reported mutation associated with SIDDT (457_458insG) was not detectable in our
      cohort. CONCLUSION: No association of sequence variations in the TSPYL1 gene and
      SIDS has been found in a German cohort. Genetic analysis of TSPYL1 seems to be of
      limited significance in the differential diagnosis of SIDS without dysgenesis of
      the testes.

PMID- 16418601
TI  - Robinow syndrome with variable neurologic features.

PMID- 16418602
TI  - Sex-influenced autosomal dominant optic atrophy is caused by mutations of IVS9
      +2A>G in the OPA1 gene.

PMID- 16418604
TI  - Use of a pediatric observation unit for treatment of children with dehydration
      caused by gastroenteritis.
AB  - OBJECTIVE: Observation units (OUs) have emerged as a cost-saving alternative to
      traditional ward admission for many pediatric illnesses. Dehydration caused by
      gastroenteritis is a common reason for admission to a pediatric OU. In this
      study, we describe characteristics of patients with presumed gastroenteritis
      admitted to a pediatric OU and seek to identify factors associated with unplanned
      inpatient admission, defined as the inability to discharge an OU patient within
      24 hours. METHODS: Retrospective cohort chart review with nested case-control
      study of children admitted to a pediatric OU from August 2000 to July 2001 for
      treatment of dehydration caused by vomiting or diarrhea from presumed
      gastroenteritis. Controls were defined as patients in the cohort who were
      successfully discharged within 24 hours from the OU; cases were defined as those
      requiring unplanned inpatient admission. RESULTS: Four hundred sixty-seven
      admissions were reviewed; 430 OU admissions involving 417 patients met criteria
      for inclusion. Patients' mean age was 1.8 years (median, 1.2 years), and 55% were
      boys. Patients presented with both diarrhea and vomiting in 77% of cases, and 72%
      had experienced symptoms for 48 hours before presentation. Nineteen percent of
      patients had temperatures greater than 38 degrees C; 25% had an anion gap of
      greater than 14; 37% had serum bicarbonate less than 15 mmol/L, and 10% had serum
      sodium less than 135 or greater than 145 mmol/L. Unplanned inpatient admission
      was required in 19% of patients. We found no significant association between
      specific historical, physical examination, and laboratory characteristics and
      need for an unplanned inpatient admission. CONCLUSION: Most patients with
      dehydration caused by gastroeneritis who need more treatment and observation than
      can reasonably be offered in an emergency department setting should be considered
      for OU admission regardless of their historical or laboratory characteristics.

PMID- 16418605
TI  - Restraint use for psychiatric patients in the pediatric emergency department.
AB  - BACKGROUND: Restraint of children and adolescents with psychiatric problems has
      generated controversy. Restraint may be defined as methods used to restrict
      movement or normal access to one's body. Published data to guide restraint
      practice are limited. OBJECTIVE: To examine frequency of restraint use and
      patient demographics and chief complaints associated with restraint use in our
      pediatric emergency department. METHODS: We retrospectively reviewed the
      pediatric emergency department records of children (age <18 years) who underwent
      emergency psychiatric evaluation in an urban general hospital from January 2001
      to December 2002. Factors associated with restraint use were determined using
      multivariate logistic regression. RESULTS: Data were available for 1125 (82%) of
      1371 patients who underwent emergency psychiatric evaluation; 76 (6.8%) of 1125
      patients were restrained: 37 physical, 19 with medication, and 20 both. Study
      patients were mean age 13.1 years, 50% girls, 54% blacks, 19% Latinos, and 18%
      whites; 80% had public insurance. Boys were restrained more often than girls
      (8.7% vs. 5.2%, P = 0.02). Age, insurance, and race were not associated with
      restraint use. Patients admitted for inpatient psychiatric care were restrained
      more frequently than those discharged home (9.9% vs. 3.9%, P < 0.001). In
      multivariate logistic regression, sex was not associated with restraint use.
      Restraint use was associated with chief complaints of visual hallucinations (odds
      ratio, 5.29), out-of-control behavior (odds ratio, 4.65), hyperactivity (odds
      ratio, 2.26), and admission to a psychiatric facility (odds ratio, 2.40).
      CONCLUSIONS: Approximately 1 in 15 children undergoing psychiatric evaluation
      were restrained. This is the first study to elucidate correlates of restraint
      practice in the pediatric emergency department. Further studies examining
      indications for restraint and comparing methods of restraint are needed.

PMID- 16418606
TI  - Young children's perceptions of physicians wearing standard precautions versus
      customary attire.
AB  - OBJECTIVE: The aim of the study was to determine if young children have a
      preference regarding whether physicians wear standard precautions attire.
      METHODS: One hundred ninety-seven children, aged 4 to 8 years, and their parents
      were recruited from the pediatric emergency department of a tertiary care center.
      Two sets of 4 photographs-the same man in formal attire, a white coat, greens,
      and severe acute respiratory syndrome (SARS) standard precautions attire, and the
      same woman in formal attire, a white coat, greens, and SARS standard precautions
      attire-were shown to the children and their caregiver. Both were asked which
      physician's attire he or she liked the most and which he or she liked the least.
      Parents filled out a questionnaire regarding their experiences in the pediatric
      emergency department during the SARS epidemic. RESULTS: The children selected the
      physician in SARS standard precautions attire as most liked 17.5% of the time and
      least liked 53.3% of the time. The parents selected the physician in SARS
      standard precautions attire as most liked 0% of the time and least liked 94.8% of
      the time. CONCLUSIONS: Physicians wearing standard precautions attire while
      working in the pediatric emergency department need to be aware that this attire
      may negatively impact their relationship with pediatric patients 4 to 8 years of
      age.

PMID- 16418607
TI  - Analgesia administration for acute abdominal pain in the pediatric emergency
      department.
AB  - OBJECTIVE: To document the use of analgesia for children with acute abdominal
      pain in the Pediatric Emergency Department (PED) and to compare between children
      with suspected appendicitis in a high versus low probability. STUDY DESIGN:
      Patients 0-16 years recruited prospectively as part of another PED study in
      Toronto. History of present illness and physical examination was available, and
      information on analgesia administered in the PED was retrospectively collected
      from charts. Physicians' probability of appendicitis before any imaging was
      recorded. A follow-up call was made to verify final diagnosis. RESULTS: We
      included 438 patients, 16% with appendicitis. Analgesics were given 154 times to
      112 patients. Thirty-one percent of the cohort received analgesia before seeing
      the physician, mostly febrile, 37% after seeing the physician, and 17% after
      seeing a pediatric-surgery consultant. Fifteen percent received multiple dosages.
      Underdosing was recorded in 14% of medications, mostly morphine (24%). Analgesia
      was given significantly more often to children with high probability of
      appendicitis. Age was not a factor in analgesia administration. CONCLUSION:
      Children with abdominal pain receive more analgesia when the physician suspects
      appendicitis, yet only in half of the cases, and only 15% receive opioids. Opioid
      underdosing happens in a quarter of times it is given.

PMID- 16418608
TI  - Nonurgent use of a pediatric emergency department: a preliminary qualitative
      study.
AB  - OBJECTIVES: To understand patterns of decision making among families presenting
      to a pediatric emergency department (ED) for nonacute care and to understand
      pediatric ED staff responses. METHODS: Cross-sectional qualitative study using in
      depth interviews, direct observations, and nonidentifying demographic data.
      RESULTS: Eleven percent of visits made during the study period were identified as
      nonacute. All were made by families from low-income areas. Three main themes
      emerged: (1) most families had been referred by their primary care providers; (2)
      the complexity of living in low-income areas makes the ED a choice of convenience
      for these stressed families; and (3) mistrust of primary health services was not
      identified by our respondents as a motivator for ED utilization, in contrast with
      other published data. Two themes emerged from ED staff: (1) actual nonurgent
      visit rates were lower than staff estimates; and (2) these visits produced
      frustration among staff members, although their degrees of insight and
      understanding of factors motivating these visits were variable. CONCLUSIONS: In
      this setting, nonacute visits occurred with lower than perceived frequency and
      caused disproportionate frustration among staff and families. These visits appear
      to be driven more by consequences of system design and structure than by family
      members' decision making. Mistrust of primary care services was not a strong
      family decision-making factor; the study's setting may have limited its ability
      to capture such data. Recommended system changes to lower barriers to primary
      care include expanded office hours, subsidized staffing for offices in medically
      underserved areas, and lowering barriers to sick care.

PMID- 16418609
TI  - Signs and symptoms of cerebrospinal fluid shunt malfunction in the pediatric
      emergency department.
AB  - OBJECTIVES: Pediatric patients with cerebrospinal fluid shunts frequently present
      to the emergency department for evaluation of possible shunt malfunction. Most
      shunt studies appear in the neurosurgical literature. To our knowledge, none have
      reviewed presenting signs and symptoms of shunt malfunction in patients who
      present to the pediatric emergency department. The study objective was to
      evaluate the medical record of children with cerebrospinal fluid shunts who
      presented to a pediatric emergency department to determine if any signs and/or
      symptoms were predictive of shunt malfunction. METHODS: A retrospective chart
      review was conducted on 352 pediatric patients aged 0 to 18 years, who presented
      to the pediatric emergency department between January 1, 1998, and December 31,
      2002, with signs and/or symptoms that prompted an evaluation for possible shunt
      malfunction. RESULTS: Univariate analysis of all signs and symptoms revealed
      lethargy (odds ratio, 1.99; 95% confidence interval, 1.15-3.42; P = 0.02) and
      shunt site swelling (odds ratio, 2.56, 95% confidence interval, 1.08-6.07, P =
      0.03) to be significantly predictive of shunt malfunction. Logistic regression
      analysis continued to show significance for lethargy (odds ratio, 2.20; bias
      corrected 95% confidence interval, 1.11-3.63) and shunt site swelling (odds
      ratio, 3.10; bias-corrected 95% confidence interval, 1.38-9.05), but found no
      other study variable to be significant. Bootstrap resampling validated the
      importance of the significant variables identified in the regression analysis.
      CONCLUSIONS: In this study, lethargy and shunt site swelling were predictive of
      shunt malfunction. Other signs and symptoms studied did not reach statistical
      significance; however, one must maintain a high index of suspicion when
      evaluating children with an intracranial shunt because the presentation of
      malfunction is widely varied. A missed diagnosis can result in permanent
      neurological sequelae or even death.

PMID- 16418610
TI  - Sudden death in an infant revealing atypical Kawasaki disease.
AB  - We present a case of a 4-month-old girl referred to the emergency department with
      a provisional diagnosis of acute life-threatening event with a recent episode of
      heart block and a history of long-lasting fever. Soon after admission, the child
      suddenly deteriorated rapidly; she became pulseless with complete heart block and
      died despite intensive resuscitation efforts. Postmortem examination showed
      coronary arteritis with aneurysmal dilatation and coronary thrombosis, revealing
      atypical Kawasaki disease. With this case presentation, we discuss the importance
      of early recognition and treatment of atypical and/or incomplete forms of
      Kawasaki disease, which are most common in young infants and may lead, if
      untreated, to coronary artery abnormalities with a potential for myocardial
      infarctions, aneurysm formation, and sudden death. In addition, the relevance of
      postmortem examination in a case of sudden and undiagnosed infant death is
      underlined.

PMID- 16418611
TI  - A 4-month-old with urate crystals and failure to thrive.

PMID- 16418612
TI  - Clothesline injury mechanism associated with all-terrain vehicle use by children.
AB  - OBJECTIVES: Clothesline injury to the face and neck is a unique mechanism of
      injury seen in children and adolescents on all-terrain vehicles (ATVs). The
      purpose of this study was to describe this serious and avoidable injury pattern.
      METHODS: A search was made of the trauma registry at a major pediatric referral
      hospital for the years 1998 to 2003 to find cases of clothesline injury
      associated with ATV use. The data were deidentified and compiled by the research
      group. The study was deemed exempt by the local institutional review board.
      RESULTS: Seven cases of neck and/or facial injury were found associated with a
      child or adolescent on an ATV striking a wire fence or clothesline. All patients
      were white, including 5 boys and 2 girls. The mean age was 8 years (range, 2-14
      years). In most cases (5/7), the child was driving across a field when the wire
      fence was struck. All patients had significant neck and/or facial lacerations,
      and 5 of 7 patients were taken to the operating room for wound closure. One
      patient had functional impairment, and all had lasting disfigurement. The mean
      initial hospital charges were US22,843 dollars. CONCLUSIONS: Clothesline injury
      to the neck and face associated with ATV use in children and adolescents is a
      unique and serious injury mechanism. Because all of these injuries in our series
      occurred in young children or adolescents who were driving or riding on the front
      of the ATV, it emphasizes the recommendation that children and young adolescents
      should not ride or drive ATVs.

PMID- 16418613
TI  - Necrotizing fasciitis caused by Aeromonas hydrophilia in an immunocompetent
      child.
AB  - Necrotizing fasciitis is a rapidly progressive and potentially fatal infection.
      It is characterized by extensive subcutaneous and muscle necrosis. Aeromonus
      hydrophilia is a gram-negative faculatively anaerobic bacillus that is part of
      the normal flora of nonfecal sewage and is found in most water systems, soil, and
      fresh brackish water. Necrotizing fasciitis caused by A. hydrophilia have
      occurred in children who had underlying systemic diseases or immune dysfunction.
      We report a 14-year-old boy without underlying systemic diseases or
      immunodeficiency who developed necrotizing fasciitis secondary to A. hydrophilia
      and he was successfully treated with extensive surgical debridement and systemic
      antibiotics.

PMID- 16418614
TI  - PTU-associated vasculitis in a girl with Turner Syndrome and Graves' disease.
AB  - Palpable purpura is a concerning clinical finding in pediatric patients and can
      have many causes, including infectious and autoimmune processes. A rare cause,
      drug-induced vasculitis, may result from the production of antineutrophil
      cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with
      Turner syndrome and Graves' disease who presented with palpable purpuric lesions.
      The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by
      observation of consistent clinical features, the detection of elevated ANA and
      ANCA in the blood, and the observed clinical resolution of symptoms following
      withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with
      radioablation did not result in an exacerbation of the vasculitis, a complication
      described in prior case reports.

PMID- 16418615
TI  - A child with palpable supraclavicular node.

PMID- 16418616
TI  - Football injury to the back.

PMID- 16418617
TI  - Evaluation of a Web-based education program on reducing medication dosing error:
      a multicenter, randomized controlled trial.
AB  - CONTEXT: The Broselow Pediatric Resuscitation Tape has been shown to be effective
      in reducing medication dosing error among pediatric emergency providers. However,
      the tape has often been used inappropriately or incorrectly. OBJECTIVE: To
      evaluate whether a Web-based education program on proper use of the tape could
      reduce medication dosing errors and time to determine dose. DESIGN, SETTING, AND
      PARTICIPANTS: A randomized, controlled trial conducted among 89 pediatric
      emergency providers from 3 study sites. INTERVENTION: All study subjects
      participated in a videotaped simulated stabilization scenario and were then
      randomly assigned to control or education group. After the intervention, all
      subjects participated in another simulation. MAIN OUTCOMES MEASURES: The primary
      outcomes included dosing deviation from accepted dose range for each medication
      prescribed and dosing deviation summary, calculated by averaging dosing deviation
      for all medications. The secondary outcomes included time to determine a dose for
      each medication prescribed, and dosing time summary; that is, the average time to
      determine doses for all medications prescribed. RESULTS: No significant
      difference was observed in the demographic characteristics of the 2 groups. After
      the educational intervention, the average (12.6% vs. 24.9%) and median (7.1% vs.
      20.1%) dosing deviation summary were much lower in the education group than in
      the control group. The difference in the median dosing deviation summary between
      the 2 groups was statistically significant (P = 0.0002). Similar results were
      observed for the dosing time. The education group demonstrated a lower average
      (16 vs. 20 seconds) and lower median (15 vs. 18 seconds) dosing time summary than
      the control group. The difference in the median dosing time summary between the 2
      groups was statistically significant (P = 0.02). Analysis of each medication
      prescribed indicated that the decrease in the dosing deviation and dosing time in
      the education group was most obvious for several specific medications.
      CONCLUSIONS: The Web-based education program on the proper use of the Broselow
      Pediatric Resuscitation Tape could improve dosing accuracy and reduce dosing
      time.

PMID- 16418620
TI  - ECGs in the ED.

PMID- 16418621
TI  - Pediatric emergency medicine: legal briefs.

PMID- 16418618
TI  - Understanding genomics: implications for the emergency medicine physician and the
      treatment of asthma.

PMID- 16418622
TI  - Mechanical stiffness of segmental versus nonsegmental pedicle screw constructs:
      the effect of cross-links.
AB  - STUDY DESIGN: A biomechanical study in porcine spines of the construct stiffness
      effects of segmental pedicle screws. Stiffness effects of supplementation of
      nonsegmental screw constructs with cross-links was also evaluated. OBJECTIVE: To
      assess the biomechanical differences between constructs using segmental versus
      nonsegmental pedicle screw-based instrumentation as well as the effect of cross
      links. SUMMARY OF BACKGROUND DATA: An in vitro biomechanical comparison of
      segmental versus nonsegmental pedicle screw constructs with and without cross
      links using porcine lumbar vertebrae was performed. Mechanical trade-offs of
      reducing the number of pedicle screws in a given construct and substituting a
      cross-link for a pair of screws are not well understood. METHODS: Three, 4, and 5
      vertebral segments from 18 porcine spines were instrumented with segmental and
      nonsegmental pedicle screw constructs, and with nonsegmental screws augmented
      with cross-links. Unconstrained biomechanical testing in flexion, extension, and
      axial rotation with 6 degree-of-freedom motion tracking was performed.
      Statistical comparisons of stiffness data were conducted using 2-tailed paired t
      tests. RESULTS: There was a statistically significant increase in stiffness
      between models with segmental pedicle screws compared to nonsegmental pedicle
      screws in 6 of the 9 mechanical tests. The remaining 3 tests approached but did
      not reach statistical significance (P = 0.087, 0.062, and 0.078). When cross
      links were added to the nonsegmental models, differences in stiffness compared to
      segmental pedicle screws were largely eliminated, decreasing well below
      statistical significance in 8 of 9 tests. The highest difference in nonsegmental
      models with cross-links and segmental pedicle screw models was observed for the 5
      vertebrae fusion models, for which axial rotation testing maintained
      statistically significant differences (P = 0.006), and flexion testing approached
      significance (P = 0.062). CONCLUSIONS: Segmental pedicle screw constructs
      increased mechanical stiffness compared to nonsegmental constructs in our fusion
      models. Placement of a single cross-link with nonsegmental screws eliminated
      statistical differences for 3 and 4-vertebral level constructs, and may be a
      satisfactory alternative in this clinical setting. Caution in applying these
      results inlonger constructs is recommended, given persistent increased stiffness
      found for the segmental 5-vertebral level models.

PMID- 16418623
TI  - Radiographic analysis of intervertebral separation with a 0 degrees and 30
      degrees rope angle using the Saunders cervical traction device.
AB  - STUDY DESIGN: Radiographic analysis of cervical intervertebral separation, (IVS)
      while using the Saunders Cervical Traction Device (SCTD) (Chattanooga Corp.,
      Chattanooga, TN) on a healthy population. OBJECTIVE: To determine whether a rope
      angle of 0 degrees or 30 degrees achieves higher posterior and anterior IVS when
      using the SCTD. SUMMARY OF BACKGROUND DATA: To our knowledge, research using a 0
      degrees rope angle and the SCTD has not been documented. METHODS: A convenience
      sample of 15 females and 5 males, with no history of cervical dysfunction,
      trauma, or pain, participated in the study. Static mechanical cervical traction,
      using the SCTD at a 0 degrees rope angle, was applied for 2 minutes using 11.34
      kg (25 lb) of force. A cross-table lateral cervical spine radiograph was obtained
      before traction and again at 2 minutes of traction. Two weeks later, the subjects
      underwent the same procedure with the rope angle set at 30 degrees . RESULTS: A 0
      degrees rope angle produced a significant mean difference in anterior IVS at all
      cervical segments as compared to a 30 degrees rope angle. Traction measurements
      comparing posterior IVS at 0 degrees and 30 degrees were not statistically
      significant. However, the posterior IVS increased significantly at a 0 degrees
      rope angle, with the exception of C2-C3. CONCLUSIONS: The research findings may
      have treatment implications when applying cervical traction with the SCTD.
      Further research using subjects with cervical nerve root compression will need to
      be conducted to substantiate clinical outcomes.

PMID- 16418624
TI  - Primary and coupled cervical movements: the effect of age, gender, and body mass
      index. A 3-dimensional movement analysis of a population without symptoms of neck
      disorders.
AB  - STUDY DESIGN: Exploratory experimental design. OBJECTIVES: To examine primary and
      coupled cervical movements, and to study the effects of age, gender, and body
      mass index in a "neck-healthy" population. These data could serve as a basis for
      future interventions and to assess normal variations. SUMMARY OF BACKGROUND DATA:
      Cervical movements are biomechanically and neurophysiologically complex. Neck
      disorders and trauma most often influence cervical movements. With 3-dimensional
      recordings, it is possible to make precise, noninvasive evaluations of how the
      head moves on the stable trunk, and to analyze primary and coupled movements.
      METHODS: A total of 120 subjects (60 men and 60 women, ages 20-79), were tested
      with Zebris (Zebris Medizintechnik GmbH, Isny, Germany), a 3-dimensional movement
      analyzer. RESULTS: Age influences the majority of primary and coupled movements.
      With increasing age, primary movement size decreases in all cardinal planes. Age
      most strongly affects the coupled movements of primary rotation and lateral
      flexion. Gender and body mass index have only slight influences. CONCLUSIONS:
      Coupled movements are a natural part of cervical motion together with primary
      movements and follow specific patterns in subjects with no symptoms of neck
      disorders. Our study shows that cervical motion alters throughout life according
      to specific patterns but with individual variations.

PMID- 16418625
TI  - Head repositioning accuracy in patients with whiplash-associated disorders.
AB  - STUDY DESIGN: Controlled study, measuring head repositioning error (HRE) using an
      electrogoniometric device. OBJECTIVE: To compare HRE in neutral position, axial
      rotation and complex postures of patients with whiplash-associated disorders
      (WAD) to that of control subjects. SUMMARY OF BACKGROUND DATA: The presence of
      kinesthetic alterations in patients with WAD is controversial. METHODS: In 26
      control subjects and 29 patients with WAD (aged 22-74 years), head kinematics was
      sampled using a 3-dimensional electrogoniometer mounted using a harness and a
      helmet. All tasks were realized in seated position. The repositioning tasks
      included neutral repositioning after maximal flexion-extension, eyes open and
      blindfolded, repositioning at 50 degrees of axial rotation, and repositioning at
      50 degrees of axial rotation combined to 20 degrees of ipsilateral bending. The
      flexion-extension, ipsilateral bending, and axial rotation components of HRE were
      considered. A multiple-way repeated-measures analysis of variance was used to
      compare tasks and groups. RESULTS: The WAD group displayed a reduced flexion
      extension range (P = 1.9 x 10(-4)), and larger HRE during flexion-extension and
      repositioning tasks (P = 0.009) than controls. Neither group nor task affected
      maximal motion velocity. Neutral HRE of the flexion-extension component was
      larger in blindfolded condition (P = 0.03). Ipsilateral bending and axial
      rotation HRE components were smaller than the flexion-extension component (P =
      7.1 x 10(-23)). For pure rotation repositioning, axial rotation HRE was
      significantly larger than flexion-extension and ipsilateral bending repositioning
      error (P = 3.0 x 10(-23)). Ipsilateral bending component of HRE was significantly
      larger combined tasks than for pure rotation tasks (P = 0.004). CONCLUSIONS: In
      patients with WAD, range of motion and head repositioning accuracy were reduced.
      However, the differences were small. Vision suppression and task type influenced
      HRE.

PMID- 16418626
TI  - Segmental spinal dysgenesis: case report of a 50-year follow-up after surgery at
      age 3 years: case report.
AB  - STUDY DESIGN: Case report with ultra long-term follow-up. OBJECTIVE: To show the
      long-term positive benefits of an arthrodesis at age 3 years. SUMMARY OF
      BACKGROUND DATA: To our knowledge, there have been no previous reports of a 50
      year follow-up of a posterior spine fusion for severe congenital kyphosis and
      segmental spinal dysgenesis. METHODS: Chart and radiographic documentation of
      both the preoperative, postoperative, and 50-year follow-up. RESULTS: Solid
      arthrodesis was achieved after a pseudarthrosis repair. Major correction was
      achieved and paraplegia prevented. Despite a long fusion to the sacrum, there was
      no junctional or sacroiliac degeneration. CONCLUSIONS: Arthrodesis at age 3 years
      provided an optimal ultra long-term follow-up.

PMID- 16418628
TI  - Allograft versus no graft with a posterior multisegmented hook system for the
      treatment of idiopathic scoliosis.
AB  - STUDY DESIGN: A prospective, randomized study. OBJECTIVE: To compare the clinical
      results of posterior spinal fusion (PSF) with allograft augmentation versus no
      graft for patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF
      BACKGROUND DATA: The use of allograft has become a standard means of augmenting a
      PSF. Many studies have shown equal rates of fusion when comparing allograft with
      autogenous iliac crest. There have been no studies to directly compare the
      results obtained with allograft with those achieved without the use of any bone
      graft at all. METHODS: Ninety-one patients with AIS were randomized into two
      treatment groups. Seventy-six patients had greater than 2-year follow-up and are
      included in this review. The Allograft Group consisted of 37 patients who
      underwent a standard PSF using a multisegmented hook-screw and rod system with
      the use of corticocancellous allograft for augmentation. The No Graft Group
      included 39 patients with AIS who underwent the same procedure without any bone
      graft. All autogenous bone resulting from a thoracoplasty and any local bone (for
      example, that removed from spinous processes) was discarded in both groups.
      Patients with at least 2 years of radiographic and clinical follow-up were
      evaluated using established criteria for possible or definite pseudarthrosis.
      Treatment groups were similar with respect to age, preoperative deformity, and
      correction obtained. RESULTS: The overall definitive pseudarthrosis rate for this
      study was 1.3% (1 of 76 patients). The 1 patient with pseudarthrosis was in the
      Allograft Group (1 of 37, or 2.7%, P = 0.98 as defined by our criteria), versus
      none of 39 in the No Graft Group. Two patients in each group (5.4% in the
      Allograft Group and 5.1% in the No Graft Group) met the radiographic criteria for
      possible pseudarthrosis. This establishes a P value of 0.65 comparing risk of
      possible pseudarthrosis in the two groups. CONCLUSION: Our results suggest that a
      PSF using newer-generation multisegmented hook-screw and rod systems can be
      successful with allograft and/or local bonegraft without the use of supplemental
      autogenous bone graft (from the iliac crest or ribs) in patients with AIS.

PMID- 16418629
TI  - Applied anatomy of transoral atlantoaxial reduction plate internal fixation.
AB  - STUDY DESIGN: A C1-C2 operation by the transoral approach was simulated to study
      the anatomic stratification, various structures, and adjacent relationships. The
      anatomic parameters in relation to transoral atlantoaxial reduction plate (TARP)
      internal fixation were measured. OBJECTIVES: To study relevant anatomic features
      of the structures involved in TARP internal fixation through transoral approach
      for treating irreducible atlantoaxial dislocation, so as to provide anatomic
      basis for the clinical application of TARP. SUMMARY AND BACKGROUND DATA:
      Irreducible anterior atlantoaxial dislocation (IAAD) with ventral spinal cord
      compression is difficult for surgical correction. Despite previous description of
      direct plate internal fixations through the transoral approach, the problem has
      not been fully resolved: the Harms' plate lacked a locking mechanism while the
      other plates unable to achieve immediate reduction of the atlantoaxial joint. We
      therefore designed the TARP system with which the decompression, reduction,
      internal fixation, and fusion procedures could be completed in the same transoral
      approach. The anatomic structures and stratification involved in the transoral
      approach, which were seldom addressed in previous anatomic studies, need to be
      clarified for internal fixation with TARP system. METHODS: Twenty fresh
      craniocervical specimens were microsurgically dissected layer by layer according
      to a transoral approach. Stratification of the posterior pharyngeal wall, course
      of the vertebral artery, anatomic relationships of the adjacent structures of the
      atlas and axis, and closely relevant anatomic parameters for TARP internal
      fixation were measured. RESULTS: The posterior pharyngeal wall consisted of two
      layers and two interspaces: the mucosa, prevertebral fascia, retropharyngeal
      space, and prevertebral space. The range from the anterior edge of the foramen
      magnum to C3 could be exposed by this approach. The thickness of the posterior
      pharyngeal wall was 3.6 +/- 0.3 mm (range, 2.9-4.3 mm) at the anterior tubercle
      of C1, 6.1 +/- 0.4 mm (range, 5.2-7.1 mm) at lateral mass of C1 and 5.5 +/- 0.4
      (range, 4.3-6.5 mm) at the central part of C2, respectively. The distance from
      the incisor tooth to the anterior tubercle of C1, C1 screw entry point, and
      C2screw entry point was 82.5 +/- 7.8 mm (range, 71.4-96.2 mm), 90.1 +/- 3.8 mm
      (range, 82.2-96.3 mm), and 89.0 +/- 4.1 mm (range, 81.3-95.3 mm), respectively.
      The distance between the vertebral artery at atlas and the midline was 25.2 +/-
      2.3 mm (range, 20.4-29.7 mm) and that between the vertebral artery at the axis
      and the midline was 18.4 +/- 2.6 mm (range, 13.1-23.0 mm). The allowed width of
      the atlas and axis for exposure was 39.4 +/- 2.2 mm (range, 36.2-42.7 mm) and
      39.0 +/- 2.1 mm (range, 35.8-42.3 mm), respectively. The distance (a) between the
      two atlas screw insertion points (center of anterior aspect of C1 lateral mass)
      was 31.4 +/- 3.3 mm (range, 25.4-36.6 mm). The vertical distance (b) between the
      line connecting the two C1 screw entry points and that connecting the two C2
      screw entry points (at the central part of the vertebrae, namely, 3 to 4 mm
      lateral to the midline of C2 vertebrae) was 21.3 +/- 2.7 mm (range, 19.4-24.3
      mm), with an a/b ratio of 1.3 to 1.5. The screws of TARP had a lateral tilt of
      12.2 degrees +/- 0.4 degrees (range, 10.2 degrees -14.6 degrees ) at C1 and a
      medial tilt of 7.3 degrees +/- 0.3 degrees (range, 5.1 degrees -9.4 degrees ) at
      C2 relative to the coronal plane. CONCLUSION: An atlantoaxial surgery through
      transoral approach is safe and feasible. This approach is suitable for an
      anterior TARP internal fixation, and the design of the internal fixation system
      should be based on the above anatomic data.

PMID- 16418630
TI  - Unilateral enucleation affects the laterality but not the incidence of scoliosis
      in pinealectomized chicken.
AB  - STUDY DESIGN: Randomized prospective study using an experimental scoliosis model
      in a pinealectomized chicken. OBJECTIVE: To investigate the effect of the side of
      visual impairment on the incidence and laterality of the curves on a
      pinealectomized chicken model. SUMMARY OF BACKGROUND DATA: Visual impairment has
      been shown to increase the incidence of idiopathic-like scoliosis in human
      subjects when compared to the incidence of the general population. However, an
      association between the laterality of the visual impairment and incidence or
      laterality of scoliosis has not been established. METHODS: A total of 60 newly
      hatched white leghorn chicks was divided equally into 3 study groups of no visual
      impairment (n = 20) (group 1), left-sided blindness by enucleation (n = 20)
      (group 2), and right-sided blindness (n = 20) (group 3). Pinealectomies and
      enucleations were performed on the second day after hatching. Anteroposterior
      radiographs were obtained at the 5th and 10th weeks, and the incidence, side, and
      magnitude of the resulting scoliotic curves were recorded. RESULTS: The
      pinealectomy model yielded a general scoliosis incidence of 60%. The occurrence
      of scoliosis was not different among the groups (65%, 55%, 60%, respectively, P =
      0.812). The incidences at the 5th and 10th weeks were both 40%, as a result of
      the death of 6 chickens between the 5th and 10th weeks, as well as the appearance
      or disappearance of curves during this time, again not different among the
      groups. However, the laterality of the curves was significantly different (P =
      0.045). The visually impaired groups tended to have left thoracic curves as
      frequently as the right thoracic curves (7 right and 4 left in group 2, and 7
      right and 6 left in group 3), whereas in group 1, the thoracic curves were
      predominantly right sided (12 right and 1 left). The average magnitude of the
      curves was 30.47 degrees +/- 19.32 degrees , not significantly different among
      the groups (27.6 degrees +/- 16.7 degrees , 23.7 degrees +/- 21.5 degrees , 39.8
      degrees +/- 17.7 degrees , respectively, P = 0.109). CONCLUSIONS: Unilateral
      visual impairment does not have a significant effect on the overall incidence and
      magnitude of scoliosis in the pinealectomized chicken. It does affect the
      laterality of the curves though, visually impaired subjects having a
      significantly higher likelihood of left thoracic curves, regardless of the side
      of blindness. It may be worthwhile to see if such an association is present in
      human beings as well.

PMID- 16418631
TI  - Intradiscal thermal therapy does not stimulate biologic remodeling in an in vivo
      sheep model.
AB  - STUDY DESIGN: Thermal energy was delivered in vivo to ovine cervical discs and
      the postheating response was monitored over time. OBJECTIVES: To determine the
      effects of two distinctly different thermal exposures on biologic remodeling: a
      "high-dose" regimen intended to produce both cellular necrosis and collagen
      denaturation and a "low-dose" regimen intended only to kill cells. SUMMARY OF
      BACKGROUND DATA: Thermal therapy is a minimally invasive technique that may
      ameliorate discogenic back pain. Potential therapeutic mechanisms include
      shrinkage of collagenous tissues, stimulation of biologic remodeling, and
      ablation of cytokine-producing cells and nociceptive fibers. METHODS: Intradiscal
      heating was performed using directional interstitial ultrasound applicators.
      Temperature and thermal dose distributions were characterized. The effects of
      high (>70 C, 10 minutes) and low (52 C-54 C, 10 minutes) temperature treatments
      on chronic biomechanical and architectural changes were compared with sham
      treated and control discs at 7, 45, and 180 days. RESULTS: The high-dose
      treatment caused both an acute and chronic loss of proteoglycan staining and a
      degradation of biomechanical properties compared with low-dose and sham groups.
      Similar amounts of degradation were observed in the low-dose and sham-treated
      discs relative to the control discs at 180 days after treatment. CONCLUSIONS:
      While a high temperature thermal protocol had a detrimental effect on the disc,
      the effects of low temperature treatment were relatively minor. Thermal therapy
      did not stimulate significant biologic remodeling. Future studies should focus on
      the effects of low-dose therapy on tissue innervation and pro-inflammatory factor
      production.

PMID- 16418632
TI  - Auditory startle alters the response of human subjects exposed to a single
      whiplash-like perturbation.
AB  - STUDY DESIGN: Human volunteers were exposed to a single whiplash-like
      perturbation. OBJECTIVE: To determine how muscle and kinematic responses are
      affected by the superposition of a rear-end collision and loud startling noise.
      SUMMARY OF BACKGROUND DATA: Many whiplash studies use forward perturbations
      without reproducing the sound of a car crash. Loud sounds are known to evoke
      startle responses in the neck muscles and therefore could affect whiplash
      injuries. METHODS: Sixty-five subjects (30 female, 35 male) were exposed to a
      single forward horizontal perturbation. Head and torso kinematics, and
      electromyographic activity in the sternohyoid, sternocleidomastoid, scalenus, and
      cervical paraspinal muscles were measured. Two awareness conditions (deceived and
      unaware subjects) nested in two startle conditions (with or without a 40
      milliseconds, 124 dB sound) were tested. RESULTS: Startle and gender affected the
      amplitude and timing of numerous kinematic and muscle variables. Awareness
      affected only one muscle variable. Startled individuals exhibited greater peak
      head and trunk accelerations, increased activity of the cervical paraspinal
      muscles, and a reduced head retraction and trunk angle. CONCLUSIONS: An acoustic
      startle alters the neck muscle and kinematic responses and may be as important as
      gender in the genesis of whiplash injury.

PMID- 16418633
TI  - Kinematics of the cervical spine in lateral bending: in vivo three-dimensional
      analysis.
AB  - STUDY DESIGN: Kinematics of the cervical spine during lateral bending were
      investigated using a novel system of three-dimensional motion analysis.
      OBJECTIVES: To demonstrate in vivo intervertebral coupled motions of the cervical
      spine during lateral bending of the neck. SUMMARY OF BACKGROUND DATA: No previous
      studies have successfully documented in vivo three-dimensional intervertebral
      motions of the cervical spine during lateral bending. METHODS: Twelve healthy
      volunteers underwent three-dimensional magnetic resonance imaging (MRI) of the
      cervical spine in 7 positions with 10 degrees increments of lateral bending.
      Relative motions of the cervical spine were calculated automatically by
      superimposing a segmented three-dimensional-MRI of the vertebra in the neutral
      position over images of each position using volume registration. RESULTS: Mean
      maximum lateral bending of the cervical spine to one side was 1.6 degrees to 5.7
      degrees at each level. Coupled axial rotation opposite to lateral bending was
      observed in the upper cervical levels (Oc-C1, 0.2 degrees ; C1-C2, 17.1 degrees
      ), while in the subaxial cervical levels, it was observed in the same direction
      as lateral bending except for at C7-T1. Coupled flexion-extension motion was
      small at all vertebral levels (<1.1 degrees). CONCLUSIONS: We succeeded in
      identifying in vivo coupled motions of the cervical spine in lateral bending for
      the first time.

PMID- 16418634
TI  - The radiographic results and neurologic complications of instrumented reduction
      and fusion of high-grade spondylolisthesis without decompression of the neural
      elements: a retrospective review of 44 patients.
AB  - STUDY DESIGN: A retrospective review of all cases of high-grade spondylolisthesis
      treated by 1 surgeon between the years 1991 and 2003. OBJECTIVE: To report the
      radiographic results and neurologic complications following instrumented
      posterior reduction and fusion without decompression of the neural elements.
      SUMMARY OF BACKGROUND DATA: Despite a large number of published reviews of the
      clinical results of operative intervention, controversy remains about the
      surgical treatment of high-grade spondylolisthesis. METHODS: A retrospective
      review of the clinical charts and radiographs of all patients with L5-S1
      spondylolisthesis and more than 50% anterior displacement of L5 on S1 who were
      treated by the same surgical team at 1 institution. RESULTS: With this technique,
      an average reduction in the displacement of L5 on S1 from 64% to 38% was
      achieved. At a minimum 2-year follow-up (41 patients), we have detected 5 cases
      with evidence of pseudarthrosis or loss of reduction (11.4%). Overall, a
      neurologic complication rate of 9.1% occurred in this series, with a 2.3% chance
      of a persistent motor deficit. We did not detect any loss of bowel or bladder
      function after surgery. At last follow-up, and after revision procedures, we were
      able to achieve good or fair clinical results in 40 (90.9%) of 44 patients.
      CONCLUSIONS: These data suggest that a posterior instrumented reduction and
      fusion of high-grade spondylolisthesis without decompression of the neural
      elements can be accomplished with acceptable radiographic and clinical results.

PMID- 16418636
TI  - Radiographic assessment of segmental motion at the atlantoaxial junction in the
      Klippel-Feil patient.
AB  - STUDY DESIGN: A retrospective review of 33 consecutive Klippel-Feil syndrome
      (KFS) patients at a single institution. OBJECTIVES: To assess in KFS patients the
      presence and degree of radiographic segmental motion at the atlantoaxial
      junction, factors contributing to such motion, and associated clinical
      manifestations. SUMMARY OF BACKGROUND DATA: Studies suggest that abnormal
      segmentation in KFS patients may result in cervical hypermobility, increasing the
      risk of developing neurologic compromise and the need for surgical intervention.
      The use of the anterior and posterior atlantodens interval (AADI/PADI) has gained
      interest as a method for assessing atlantoaxial instability and for space
      available for the cord. Although helpful for identifying instability after
      trauma, these measurements are not understood in KFS patients. In addition, the
      effects of the fusion process associated with KFS on atlantoaxial motion and
      associated clinical findings have not been properly addressed. METHODS:
      Radiographs were analyzed for the presence of occipitalization, number/location
      of congenitally fused segments, and the AADI and PADI. RESULTS: There were 15
      males and 18 females (mean age, 13.9 years). Occipitalization occurred in 48.5%
      of patients. A fused C2-C3 segment was noted in 72.7% of cases. More motion with
      respect to AADI was evident on O-C1 and C2-C3 fusion only patients, which were
      all asymptomatic. Overall, 24.2% of patients were symptomatic. Mean AADI and PADI
      difference was 2.0 mm (symptomatic: mean, 1.5 mm; asymptomatic: mean, 2.1 mm) and
      -1.7 mm (symptomatic: mean, -1.0 mm; asymptomatic: mean, -2.0 mm), respectively
      (P > 0.05). CONCLUSIONS: Hypermobility of the atlantoaxial junction, as indicated
      by increased AADI on flexion-extension radiographs, is not necessarily associated
      with an increased risk for the development of symptoms or neurologic signs in the
      KFS patient. Occipitalization plays an integral role in the degree of motion at
      the atlantoaxial region. Greatest AADI values were in patients with
      occipitalization and a fused C2-C3 segment. The presence of symptoms was not
      related to the degree of AADI change. Evaluation of the PADI provides additional
      information for identifying patients at risk for developing symptoms.
      Nonetheless, KFS patients remain largely asymptomatic.

PMID- 16418637
TI  - A prospective study of de novo scoliosis in a community based cohort.
AB  - STUDY DESIGN: A 12-year prospective study of de novo scoliosis in a community
      based cohort. OBJECTIVE.: To investigate factors associated with development of
      de novo scoliosis. SUMMARY OF BACKGROUND DATA: De novo scoliosis is becoming one
      of the most prevalent findings in the aging spine, and this condition is
      associated not only with severe back or leg symptoms but also with complicated
      surgical outcomes. Cross-sectional studies were limited in distinguishing de novo
      scoliosis from preexisting deformities, and there had been controversies over the
      etiology of degenerative scoliosis. METHODS: Community based volunteers were
      recruited, then examined by orthopedic physicians. Radiologic measurements using
      entire spine radiographs included the angle of scoliosis and sagittal spinal
      curvatures, sagittal spinal balance, grade of bone atrophy, number of degenerated
      discs, and vertebral fractures. We defined radiologic parameters, the disc index,
      and lateral osteophyte difference to evaluate the asymmetrical spinal
      degeneration. RESULTS: A total of 60 subjects aged 50-84 years and without
      scoliosis at baseline were selected and followed for a mean of 12.0 years. De
      novo scoliosis >or=10 degrees developed in 22 subjects, and logistic regression
      analysis revealed that the baseline disc index and lateral osteophyte difference
      values were independent predictors (P < 0.05). CONCLUSIONS: Incidence of de novo
      scoliosis was predictable by assessing asymmetric disc degeneration in frontal
      radiograph. More than 20% decrease in unilateral disc height or more than 5 mm
      longer osteophyte on one side led to increased incidence of de novo scoliosis,
      which might also influence long-term results of spinal surgery.

PMID- 16418638
TI  - Regional differences in anatomical landmarks for placing anterior instrumentation
      of the thoracic spine in both normal patients and patients with adolescent
      idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective analysis of patients who had magnetic resonance
      imaging (MRI) of the thoracic spine, comparing those with a normal straight spine
      and those with a right thoracic adolescent idiopathic scoliosis (AIS). OBJECTIVE:
      To analyze the position of the rib head with respect to the spinal canal and
      vertebral body in normal patients and those with right thoracic AIS using MRI.
      SUMMARY OF BACKGROUND DATA: When placing anterior vertebral body screws in
      thoracic AIS, the most cephalad screws are most at risk for loosening because of
      smaller vertebral body size and the position of the rib heads, which may obscure
      more of the vertebral bodies. To our knowledge, there are no studies defining the
      relationship of the rib head to the vertebral anatomy in thoracic AIS. METHODS:
      Transverse MRIs of the vertebral bodies from the 4th thoracic (T4) vertebra to
      the 12th thoracic (T12) vertebra in normal patients (n = 21) and patients with
      AIS (n = 21) group were analyzed regarding the following parameters: (1) percent
      vertebra obscured by rib head (i.e., the percent of the sagittal plane vertebral
      body length obscured by the overlapping rib head); (2) posterior safe angle,
      defined as the most posterior angle a screw can be placed, which avoids the
      spinal canal; and (3) anterior safe angle, defined as the most anteriorly
      directed screw trajectory that safely obtained good screw purchase. RESULTS: In
      both the normal and AIS groups, the percent vertebra obscured by rib head
      significantly decreased from T4 (30% in normal group and 34.7% in AIS group) to
      T12 (-0.4% in normal group and 3.5% in AIS group) (P < 0.05). The rib head was
      positioned more anterior to the vertebral body in the cephalad-thoracic spine
      when compared to a more posterior position in the caudal thoracic spine. In each
      group, the posterior safe angle significantly decreased from T4 (23 degrees in
      normal group and 20.8 degrees in AIS group) to T12 (-0.9 degrees in normal group
      and 2.1 degrees in AIS group) (P < 0.05), while the anterior safe angle
      significantly increased from T4 (27.5 degrees in normal group and 26.6 degrees in
      AIS group) to T12 (38.3 degrees in normal group and 38.5 degrees in AIS group) (P
      < 0.05). CONCLUSIONS: It is important to understand the relationship of the rib
      head to the vertebral body to provide-excellent screw purchase within the
      vertebral body without risking penetration into the spinal canal. In both normal
      and AIS groups, the relationship of the rib head to the vertebral body and spinal
      canal changes so that the rib head is positioned more anteriorly in the cephalad
      thoracic spine and more posteriorly in the caudal thoracic spine. When placing
      anterior thoracic screws, at the cephalad- thoracic spine (T4, T5, T6, and T7),
      removal of rib heads is recommended to allow for good screw purchase. However, at
      the caudal thoracic spine (T10-T12), staying anterior to the rib head is
      important to avoid penetration into the spinal canal.

PMID- 16418640
TI  - Postlaminectomy kyphosis in the skeletally immature achondroplast.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVES: To determine the risk of
      postlaminectomy thoracolumbar kyphosis in skeletally immature achondroplasts and
      evaluate the need for concurrent fusion at multilevel decompression. SUMMARY OF
      BACKGROUND DATA: Spinal stenosis is a relatively common complication of
      achondroplasia. Although most achondroplasts do not develop symptomatic spinal
      stenosis until the third or fourth decades, some patients become symptomatic
      before skeletal maturity. While postlaminectomy kyphosis typically does not occur
      in the adult achondroplast, it is not known if it occurs in the skeletally
      immature achondroplast. METHODS: The charts and radiographs of 10 consecutive
      skeletally immature achondroplasts that underwent surgical treatment for
      symptomatic spinal stenosis during a 10-year period were retrospectively
      reviewed. The average age of the 6 male and 4 female patients at surgery was 9.2
      years (range 6-16). All patients had preoperative lateral radiographs.
      Decompression consisted of multilevel (5-8) thoracolumbar laminectomies. More
      than 50% of each medial facet was preserved bilaterally to maintain spinal
      stability. RESULTS: Postlaminectomy thoracolumbar kyphoses developed in all 10
      patients (100%). The postlaminectomy kyphoses ranged from 78 degrees to 135
      degrees (mean 94 degrees ). All patients underwent spinal fusions with
      instrumentation, performed from 10 months to 2.6 years after the decompressions,
      to stabilize the kyphoses. CONCLUSIONS: Skeletally immature achondroplasts are at
      high risk for developing postlaminectomy thoracolumbar kyphoses. Therefore,
      concurrent spinal fusion is indicated in skeletally immature achondroplasts who
      undergo thoracolumbar laminectomies of at least 5 levels.

PMID- 16418639
TI  - Posterolateral, anterior, or circumferential fusion in situ for high-grade
      spondylolisthesis in young patients: a long-term evaluation using the Scoliosis
      Research Society questionnaire.
AB  - STUDY DESIGN: A retrospective, comparative follow-up study. OBJECTIVE: To compare
      clinical and radiographic outcomes after posterolateral, anterior, or
      circumferential fusion in situ for high-grade spondylolisthesis in children and
      adolescents. SUMMARY OF BACKGROUND DATA: Controversial opinions still exist about
      the surgical treatment of severe isthmic spondylolisthesis. There are no long
      term comparative studies of different fusion in situ techniques in these
      patients. METHODS: A total of 21 patients treated using posterolateral, 23 using
      anterior, and 26 using the circumferential fusion technique without
      instrumentation for high-grade isthmic spondylolisthesis (>or=50% slip)
      participated. Their mean age at surgery was 14.4 years (range 8.0-19.6). The
      follow-up rate was 84% after a mean of 17.2 years (range 10.7-26.0). Radiographs
      were obtained before surgery, at 2-year follow-up, and at final follow-up. The
      Scoliosis Research Society (SRS) and Oswestry Disability Index questionnaires
      were completed, and a physical examination was performed at the final follow-up
      visit. RESULTS: Progression of lumbosacral kyphosis (>or=10 degrees ) was found
      in 9 (43%), 3 (13%), and 3 (12%) patients of the posterolateral, anterior, and
      circumferential fusion groups, respectively (P = 0.017). The SRS total score
      averaged 89.7 (range 56-105) in the posterolateral, 93.2 (range 66-114) in the
      anterior, and 100.0 (range 71-117) in the circumferential fusion groups (P =
      0.021). Patients in the circumferential fusion group had better values for pain
      (P = 0.023) and function from back condition domains (P = 0.079) than patients in
      the posterolateral or anterior groups. The Oswestry Disability Index averaged 9.7
      (range 0-62) in the posterolateral, 8.9 (range 0-32) in the anterior, and 3.0
      (range 0-16) in the circumferential fusion groups (P = 0.035). CONCLUSIONS:
      Circumferential fusion provided significantly better long-term clinical,
      radiographic, and SRS total score than posterolateral or anterior fusion for high
      grade isthmic spondylolisthesis.

PMID- 16418641
TI  - Operative treatment of scoliosis in patients with a Fontan circulation.
AB  - STUDY DESIGN: A retrospective chart and radiographic review of patients with a
      Fontan physiology who underwent surgical correction of their scoliosis.
      OBJECTIVE: To evaluate the operative and perioperative treatment of patients with
      a Fontan physiology and scoliosis. SUMMARY OF BACKGROUND DATA: The survival rates
      in patients with complex congenital heart disease are improving, thus creating a
      subset of patients with complex physiology who will require surgical treatment of
      their scoliosis. The Fontan physiology is created surgically in patients born
      with a single functioning ventricle. These patients represent a significant
      anesthetic risk during spinal surgery, given their physiologic need for a
      sustained systemic preload. Currently, to our knowledge, there are no published
      series in the literature regarding the operative treatment of scoliosis in these
      patients. METHODS: We reviewed our experience with the operative treatment of
      scoliosis in 7 patients with a Fontan circulation. There were 7 patients
      identified who were treated with correction and arthrodesis using modern
      segmental instrumentation. A radiographic and chart review was performed to
      assess the operative and perioperative treatment. RESULTS: Mean age at surgery
      was 14 years 9 months, and mean Cobb angle was 75 degrees . There were no
      intraoperative complications; however, postoperative complications were frequent
      and significant: 1 delayed paralysis, 2 superior mesenteric artery syndromes, 1
      renal tubular necrosis, 2 pulmonary complications, 1 Horner syndrome, and 1
      urinary tract infection. CONCLUSIONS: Operative treatment of scoliosis in these
      patients may be successful; however, complications are frequent and significant.

PMID- 16418642
TI  - MRI signal changes of the pedicle as an indicator for early diagnosis of
      spondylolysis in children and adolescents: a clinical and biomechanical study.
AB  - STUDY DESIGN: Clinical review of pediatric patients with lumbar spondylolysis and
      biomechanical analysis using finite-element lumbar spine model. OBJECTIVES: To
      evaluate the usefulness of the signal changes observed on MR images of the
      pedicle for the early diagnosis of spondylolysis, and to investigate the
      pathomechanism of the signal changes based on the stresses in pedicles, as
      predicted using finite-element analyses. Furthermore, to evaluate the usefulness
      of the signal change to predict the bony healing following conservative
      treatment. SUMMARY OF BACKGROUND DATA: Since early-stage spondylolysis can
      achieve osseous healing conservatively, it is important to diagnose this disorder
      as early as possible. Presently, there is no well-established, noninvasive, and
      reliable diagnostic tool for the early diagnosis. METHODS: Thirty-seven pediatric
      patients with spondylolysis were included. Sixty-eight defects were examined and
      their stages as revealed on CT scans were recorded. High signal changes (HSC) of
      the pedicles on axial T2-weighted MRI were compared with the CT-based stages of
      the defect. Among them, 16 patients, including 15 boys and 1 girl, were treated
      conservatively for at least a 3-month period. Bony healing of the fracture site
      was evaluated on CT, and the results were compared between two groups with or
      without HSC at the initial consultation. Using a three-dimensional nonlinear
      finite-element model of the L3-L5 segment, stress distributions in the pars and
      pedicle regions were analyzed in response to 400 N compression and 10.6 Nm
      moment. RESULTS: Based on CTs, 68 pars defects were classified as follows: 8 very
      early, 24 late-early, 16 progressive, and 20 terminal stages. All defects in very
      early and late-early stages (100%) showed HSC on T2-weighted MRI at the
      ipsilateral pedicle. Among 16 progressive stages, eight (50%) showed HSC, while
      no defects of the terminal stage (0%) were found to have HSC. In total, 29 pars
      defects were treated conservatively out of 16 patients. In 19 of the HSC positive
      defects, 15 (79%) showed bony healing after the conservative treatment, whereas
      none of the 10 HSC negative defects (0%) showed any healing. The results were
      statistically significant at P < 0.05 (chi). Stress results from the finite
      element model indicated that pars interarticularis showed the highest value in
      all loading modes, and the pedicle showed the second highest. CONCLUSIONS: The
      correlation between the high stresses in the pedicle and the corresponding HSC
      suggest that signal changes in MRI could be used as an indicator for early
      diagnosis of spondylolysis. The HSC of the pedicle provided useful information to
      diagnose early stage spondylolysis. Furthermore, the HSC may be a good indicator
      as to whether a bony union will result from conservative treatment.

PMID- 16418643
TI  - A population-based analysis of healthcare utilization of persons with back
      disorders: results from the Canadian Community Health Survey 2000-2001.
AB  - STUDY DESIGN: A retrospective, population-based analysis. OBJECTIVES: To analyze
      the utilization of a variety of healthcare services for persons with and without
      a chronic back disorder, and to identify factors associated with specific
      patterns of healthcare resource use. SUMMARY OF BACKGROUND DATA: Although there
      have been studies of how chronic back disorders influence the use of specific
      healthcare services, we do not currently have a broad, population-based overview
      of how this condition influences healthcare service utilization. METHODS: Person
      level data were taken from the 2000-2001 Canadian Community Health Survey (CCHS),
      a nationwide cross-sectional survey of health determinants, health status, and
      health system utilization of Canadians. A series of binary logistic regressions
      examining healthcare resource utilization were performed on a full study sample
      (n = 113,229), as well as a restricted sample (n = 36,713) with attention focused
      on subjects with a single diagnosis of a chronic back disorder. RESULTS: Persons
      with chronic back disorders were more likely to use physician resources
      (multivariate odds ratio [OR] = 1.2; 95% confidence interval, 1.1-1.2), and
      nonphysician resources (OR range, 2.1-3.6) compared with persons without the
      condition, with chiropractic care having an odds ratio of 3.6 (95% confidence
      interval, 3.5-3.8). Higher socioeconomic status, the presence of activity
      limiting pain, and depressive symptoms were associated with a significant
      increase in utilization of almost all healthcare services. CONCLUSIONS: With
      increasing disability as indicated by the presence of pain and functional
      limitations, and the presence of depressive symptoms, the higher the utilization
      of physician and nonphysician resources, with the exception of chiropractic care,
      which appears to be used by those with less severe symptoms. Lower socioeconomic
      status was associated with significantly lower receipt of services for almost all
      healthcare providers.

PMID- 16418644
TI  - Work disability and costs caused by recurrence of low back pain: longer and more
      costly than in first episodes.
AB  - STUDY DESIGN: Retrospective analysis of workers' compensation (WC) claims data
      for nonspecific low back injuries (LBI) in a single jurisdiction. OBJECTIVE: To
      examine whether recurrences, defined as post-initial episodes of work disability
      or medical care, substantially contribute to total medical and indemnity costs,
      and total duration of work disability. SUMMARY OF BACKGROUND DATA: Previous
      studies have not measured the proportion of care seeking and work disability that
      are associated with recurrences in claims for work-related LBI. METHODS: All
      persons with new lost-time claims for nonspecific LBI reported in New Hampshire
      to a large WC provider from 1996 to 1999 were selected (N = 1867). Three years of
      follow-up data, starting at the beginning of the first episode, were collected.
      Previously validated definitions of recurrence were used identify new episodes of
      care and new episodes of lost work time (work disability). Total duration of work
      disability, total medical costs, and total indemnity costs were investigated. For
      individuals with recurrences, these variables were separated into first-episode
      and recurrent period duration and costs. RESULTS: The rate of recurrent work
      disability was 17.2%, and the rate of recurrent care seeking was 33.9%.
      Individuals with recurrence had significantly higher total length of work
      disability, and higher medical and indemnity costs. For those with recurrent work
      disability, 69% of total lost time from work, 71% of associated indemnity costs,
      and 84% of total medical costs occurred during the recurrent period. For those
      with recurrence of care, the respective values were 48%, 47%, and 42%.
      CONCLUSIONS: Recurrences contributed disproportionately to the total burden of
      work-related nonspecific LBI, through both additional care seeking and work
      disability. Results imply that those who have recurrences may be an especially
      important target for secondary prevention efforts.

PMID- 16418645
TI  - School-based interventions for spinal pain: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To establish the effectiveness of
      school-based spinal health interventions in terms of: 1) improving knowledge
      about the spine/spinal care; 2) changing spinal care behaviors; and 3) decreasing
      the prevalence of spinal pain. SUMMARY OF BACKGROUND DATA: Spinal pain is a
      significant problem in children and adolescents that has been addressed through
      school-based spinal health interventions. No systematic review has been carried
      out on this topic to date. METHODS: A systematic literature review sought studies
      that evaluated school-based spinal health interventions. Using clearly defined
      study inclusion criteria, 11 databases were searched from their inception to
      March 2004. To identify further literature, three relevant journals were hand
      searched, reference lists were checked, and authors of included papers were
      contacted. Two reviewers independently appraised the quality of identified papers
      and extracted data regarding intervention and study characteristics, statistical
      analyses performed, and study results. Data were examined using a narrative
      synthesis of results, and the outcomes of interest were considered individually
      (knowledge, behaviors, pain prevalence). RESULTS: Twelve papers were included in
      this review; all papers received a "weak" quality rating. Results of these
      studies indicate that school-based spinal health interventions may be effective
      in increasing spinal care knowledge and decreasing the prevalence of spinal pain.
      However, overall the evidence is inconclusive regarding spinal care behaviors.
      CONCLUSIONS: The poor quality of the reviewed studies limits the conclusions that
      can be made regarding the effectiveness of school-based spinal health
      interventions.

PMID- 16418646
TI  - An evaluation of image-guided technologies in the placement of percutaneous
      iliosacral screws.
AB  - STUDY DESIGN: A surgical simulation study in human cadaver spine specimens was
      conducted to evaluate the accuracy of 3 different surgical navigation systems
      compared to standard fluoroscopy in the percutaneous placement of iliosacral
      screws. OBJECTIVES: To compare the accuracy of percutaneous iliosacral screw
      placement using standard fluoroscopy, computer-assisted fluoroscopic image
      guidance, Iso-C3D image guidance (Medtronic Surgical Navigation Technologies,
      Louisville, CO), and electromagnetic fluoroscopic image guidance. SUMMARY OF
      BACKGROUND DATA: Conventional percutaneous sacroiliac screw placement has a
      malposition rate as high as 15%, as reported in the English-speaking literature
      (Hinsche et al [Clin Orthop Relat Res 2002;395:135-44] and Templeman et al [Clin
      Orthop Relat Res 1996;329:194-8]). Iso-C3D and computer-assisted image guidance
      technologies have been proposed to increase this accuracy rate. METHODS: Two
      iliosacral screws were placed bilaterally (4 screws) in each of 4 cadavers using
      standard fluoroscopy, computer-assisted fluoroscopic image guidance, Iso-C3D
      image guidance, and electromagnetic fluoroscopic image guidance. Screw positions
      were analyzed by computerized tomography after instrumentation and assigned a
      score based on deviation from ideal screw position. RESULTS: The StealthStation
      with FluoroNav (Medtronic Surgical Navigation Technologies) appeared to provide
      the highest accuracy of all guidance techniques. This result was more accurate
      than standard fluoroscopy. CONCLUSIONS: Computer-assisted fluoroscopy based image
      navigation appears to be more accurate than standard fluoroscopy in placing these
      screws. However, errors may occur with all techniques. Further refinement in
      registration procedures may highly improve the accuracy of percutaneous screw
      placement in a variety of spinopelvic procedures.

PMID- 16418647
TI  - Fluoroscopically assisted surgical treatments of spinal disorders: conceptus
      radiation doses and risks.
AB  - STUDY DESIGN: A series of anterior-posterior and lateral fluoroscopic exposures
      at 5 spinal levels were performed on anthropomorphic phantoms simulating the 3
      trimesters of gestation. OBJECTIVES: To provide normalized data for the
      determination of conceptus dose specific to gestational stage and treated spinal
      level. To estimate the conceptus radiation dose and risk associated with typical
      fluoroscopically guided spinal treatments performed on the pregnant patient.
      SUMMARY OF BACKGROUND DATA: To our knowledge, there are no available data on
      conceptus doses and radiogenic risks resulting from fluoroscopically guided
      spinal surgery of the expectant mother. METHODS: Direct measurement of conceptus
      doses from simulated fluoroscopic projections involved in orthopedic surgery at
      different spinal levels for the 3 trimesters of gestation with use of
      anthropomorphic phantoms and thermoluminescent dosimetry. Estimation of conceptus
      radiation risks from a typical pedicle screw fixation and kyphoplasty procedure
      using the experimentally derived data. RESULTS: Conceptus doses from
      fluoroscopically guided spinal treatments are smaller than 4 mGy during all
      gestational stages, provided that the conceptus lies outside the primarily
      irradiated region. The associated risks of fatal cancer during childhood and
      congenital malformation on its progeny are at least 2 and 1500 times,
      respectively, lower than the spontaneous incidence rates. When the embryo is
      primarily irradiated, mean conceptus dose can be as high as 105 mGy from a
      nonoptimized exposure. At least 35 minutes of fluoroscopy are required for the
      induction of deterministic effects. CONCLUSIONS: Individual dose assessment is
      paramount in every pregnancy. Variations in fluoroscopy practices and gestational
      stage significantly affect fetal doses.

PMID- 16418649
TI  - Re: Hurwitz EL, Morgenstern H, Vassilaki M, Chiang L-M. Frequency and clinical
      predictors of adverse reactions to chiropractic care in the UCLA neck pain study.
      Spine 2005;30: 1477-84.

PMID- 16418648
TI  - A review of the 2001 Volvo Award winner in clinical studies: lumbar fusion versus
      nonsurgical treatment for chronic low back pain: a multicenter randomized
      controlled trial from the Swedish lumbar spine study group.
AB  - The current debate over the efficacy of lumbar fusion for low back pain has not
      been settled. Fritzell et al published a landmark paper entitled "Lumbar fusion
      versus nonsurgical treatment for chronic low back pain: a multicenter randomized
      controlled trial from the Swedish lumbar spine study group." Their goal was to
      provide objective evidence supporting lumbar fusion. While it was well designed
      and important to our knowledge base, it has limitations. We set out to review
      their work in an unbiased yet critical manner. Our goals are to summarize the
      strengths and weaknesses of the paper, place it in the context of current
      knowledge, and highlight its significance for present-day practice and research.
      From technical and study design perspectives, Fritzell et al were able to
      validate the use of lumbar fusion for the treatment of low back pain. However,
      their use of "usual nonoperative" care and nonspecific definition of low back
      pain precluded a truly genuine comparison of operative and nonoperative groups.
      We commend the Swedish lumbar spine study group and their remarkable efforts;
      they elevated the sophistication of spine research and spawned many more
      excellent works to help settle the ongoing controversy on the ideal treatment of
      low back pain.

PMID- 16418650
TI  - Re: Hurwitz EL, Morgenstern H, Vassilaki M, Chiang LM. Frequency and clinical
      predictors of adverse reactions to chiropractic care in the UCLA neck pain study.
      Spine 2005; 30: 1477-84.

PMID- 16418654
TI  - Re: Hurwitz EL, Morgenstern H, Vassilaki M, Chiang LM. Frequency and clinical
      predictors of adverse reactions to chiropractic care in the UCLA neck pain study.
      Spine 2005; 30: 1477-84.

PMID- 16418656
TI  - Re: Hurwitz et al. Frequency and clinical predictors of adverse reactions to
      chiropractic care in the UCLA neck pain study. Spine 2005; 30: 1477-84.

PMID- 16418657
TI  - Orbital reconstruction after eyelid- and conjunctiva-sparing orbital
      exenteration.
AB  - PURPOSE: To describe the technique and results of eyelid- and conjunctiva-sparing
      orbital exenteration with temporalis transfer and dermis-fat graft. METHODS: Five
      patients who underwent this procedure were studied, based on retrospective chart
      review. Schematic drawings were produced to illustrate the surgical technique.
      RESULTS: The study included three female and two male patients with an age range
      of 7 to 76 years. Two patients required surgery for invasive optic nerve sheath
      meningioma, one for hemangiopericytoma, and the fourth for mesenchymal
      chondrosarcoma. The last patient had eyelid-sparing exenteration performed more
      than 20 years earlier for retinoblastoma and underwent a similar reconstruction.
      One case was complicated by infection and graft atrophy. The remaining four cases
      retained orbital volume and eyelid structures with a reasonable cosmetic outcome.
      Average follow-up period was 21 months, during which one patient had development
      of intracranial meningioma at the proximal end of the optic canal. CONCLUSIONS:
      Eyelid- and conjunctiva-sparing orbital exenteration with temporalis transfer and
      dermis-fat graft is a useful technique that minimizes the usual deformity and
      achieves good results. Case selection is emphasized, as this technique is mainly
      reserved for histopathologically benign orbital lesions that exhibit local
      aggressive behavior and for malignant lesions only if there is no eyelid,
      lacrimal gland, or orbital fissure involvement nor significant conjunctival or
      deep extension of an intraocular tumor.

PMID- 16418658
TI  - Clinical features and treatment of graves ophthalmopathy in pediatric patients.
AB  - PURPOSE: To determine the clinical characteristics and review the frequencies of
      medical and surgical treatment of children with Graves ophthalmopathy. METHODS:
      Retrospective case series identifying patients 18 years or younger in whom Graves
      ophthalmopathy was diagnosed from 1985 through 1999. Data also were obtained from
      a follow-up survey. RESULTS: The 35 children with Graves ophthalmopathy included
      27 girls (77.1%) and 8 boys (22.9%). At the time of initial ophthalmic
      examination, 31 patients (88.6%) were hyperthyroid, 1 (2.9%) was hypothyroid, and
      3 (8.6%) were euthyroid. The mean age at diagnosis of thyroid dysfunction was
      13.1 years (range, 3 to 18). The mean age at diagnosis of ophthalmopathy was 15.0
      years (range, 5 to 18). No patient had compressive optic neuropathy. Thirty-one
      patients (88.6%) required no therapy or only supportive therapy. One patient
      (2.9%) required eyelid surgery and 3 (8.6%) underwent transantral orbital
      decompression for proptosis that caused discomfort and exposure keratitis. No
      patient received systemic corticosteroids or orbital radiotherapy. A follow-up
      survey was returned by 20 respondents at a mean follow-up of 11.0 years after the
      initial examination (range, 3.4 to 19.4). One patient (5.0%) had undergone eye
      muscle surgery. All patients stated that their vision was good, and 19 (95.0%)
      had no diplopia. Two patients (10.0%) reported that family members had Graves
      ophthalmopathy, and 12 (60.0%) had family members with thyroid dysfunction.
      CONCLUSIONS: The clinical manifestations of Graves ophthalmopathy are relatively
      less severe in pediatric patients. Surgical therapy is infrequently necessary.

PMID- 16418659
TI  - Longitudinal correlation of thyroid-stimulating immunoglobulin with clinical
      activity of disease in thyroid-associated orbitopathy.
AB  - PURPOSE: To investigate the possible correlation between the changes in
      inflammatory active phase of thyroid-associated orbitopathy (TAO) with measured
      changes in thyroid-stimulating immunoglobulin (TSI) levels over time. This study
      was undertaken to evaluate the potential usefulness of measured TSI values in
      following and treating patients with TAO. METHODS: A retrospective chart analysis
      was performed on 23 patients who had been referred to a tertiary care
      oculoplastics service between July of 2002 and April of 2004 with suspected TAO.
      The activity status of patients with TAO was graded by using the TAO activity
      scale (TAOS), created to distinguish between the active and cicatricial phases of
      TAO. Laboratory values of TSI reported during the course of the study period were
      compiled for each study patient. RESULTS: Linear regression analysis revealed a
      statistical correlation between the changes in activity of TAO, as measured by
      the TAOS score, and changes in measured values of TSI over time. A statistically
      significant correlation was also found between the activity of TAO (measured by
      the TAOS score) and TSI value. CONCLUSIONS: It was found that changes in
      inflammatory phase of TAO, as measured by the TAOS score, statistically correlate
      with changes in measured TSI. An additional correlation was also found between
      the absolute score of TAO activity and measured level of TSI. These findings
      suggest that serial TSI measurements may be an adjunct in assessing clinical
      inflammatory activity of TAO and may help direct clinical decision making
      regarding treatment decisions in TAO.

PMID- 16418660
TI  - Reconstruction of complex orbitocranial deformities using bioresorbable mesh,
      sterilized orbital models, and in situ contouring.
AB  - PURPOSE: To assess the efficacy of bioresorbable mesh in reconstruction of
      orbitocranial deformities. METHODS: A retrospective case series evaluating 6
      orbits of 6 patients, ages 12 to 70 years old, with large multicontoured
      orbitocranial defects that were repaired using bioresorbable macroporous mesh.
      Both functional (presence of diplopia, ocular motility, exophthalmometry, and
      vertical globe position) and cosmetic outcomes were evaluated. RESULTS: Follow-up
      time ranged from 20 to 48 months (mean, 29.1 months). After surgery, all patients
      reported cosmetically pleasing results. Diplopia resolved in all patients. Ocular
      motility, exophthalmos, enophthalmos, and vertical globe positioning improved in
      all patients. One patient had new onset of mild enophthalmos and hypoglobus after
      surgery. No cases of implant exposure or instability occurred. Complications
      included one patient with skin breakdown over a previous site of irradiation and
      one patient with ptosis requiring surgical correction. CONCLUSIONS: Bioresorbable
      macroporous mesh combined with bone grafts is a useful and accurate method to
      reconstruct complex multicontoured orbitocranial defects.

PMID- 16418661
TI  - Lower eyelid laxity in functional acquired epiphora: evaluation with quantitative
      scintigraphy.
AB  - PURPOSE: The examination of lacrimal drainage is often based on qualitative
      criteria. This study uses quantitative scintigraphy to evaluate "functional"
      epiphora. METHODS: Thirty-two patients with functional epiphora (no morphologic
      abnormalities of the conjunctiva and eyelids, a patent nasolacrimal duct on
      irrigation, and no anatomical stenosis on dacryocystography) were studied (study
      group, SG). Twenty-two individuals without epiphora were also examined (control
      group, CG). Fifty microliters of Technetium-99m was instilled into the
      conjunctival cul-de-sac. Time-activity curves were then constructed, and
      conjunctival lacrimal clearance (CLC) at 2.5, 5, 7.5, and 10 minutes was
      calculated. Differences in CLC between the SG and the CG and correlations between
      CLC and horizontal and median tendon laxity and eyelid length in the SG were
      examined. RESULTS: The SG had significantly reduced CLC at 2.5 and 5 minutes,
      compared with the CG (p = 0.01 and p = 0.04, respectively), whereas respective
      differences at 7.5 and 10 minutes were not statistically significant. In the SG,
      CLC at 2.5 and 5 minutes was significantly correlated with horizontal and median
      tendon laxity. The respective correlation with eyelid length was not
      statistically significant. Furthermore, in the SG, CLC at 2.5 and 5 minutes was
      significantly correlated with patient age (p = 0.03 and p = 0.04, respectively).
      Differences in CLC between men and women were not statistically significant at
      all intervals. CONCLUSIONS: The correlation between eyelid laxity and CLC
      supports the role of the eyelid "pump" in lacrimal drainage. CLC at 2.5 and 5
      minutes may be used to decide treatment methods for functional epiphora.

PMID- 16418662
TI  - Mucinous eccrine adenocarcinoma of the periocular region.
AB  - PURPOSE: To report 4 patients with mucinous eccrine adenocarcinoma of the
      periocular region. METHODS: Interventional case series of 4 patients with
      mucinous eccrine adenocarcinoma of the periocular region treated at 2 centers.
      RESULTS: Two patients with mucinous eccrine adenocarcinoma of the upper eyelid, 1
      with mucinous eccrine adenocarcinoma of the lower eyelid, and 1 with mucinous
      eccrine adenocarcinoma of the eyebrow were included in this report. The lower
      eyelid lesion and the eyebrow lesion recurred after Mohs micrographic surgery.
      Both recurrent lesions were treated with Mohs micrographic surgery and
      postoperative adjuvant external-beam radiation therapy. The other 2 primary
      tumors were treated with wide local excision with frozen section control of
      margins and did not recur. The follow-up time after the most recent surgical
      procedure ranged from 8 to 17 months (median, 12 months). CONCLUSIONS: Mucinous
      eccrine adenocarcinoma is a rare ocular adnexal neoplasm that can involve the
      eyelid and periocular skin, can be locally invasive, and has a high risk of local
      recurrence despite Mohs surgery.

PMID- 16418663
TI  - Local corticosteroid treatment of eyelid and orbital xanthogranuloma.
AB  - PURPOSE: To demonstrate the efficacy of local corticosteroid therapy for the
      treatment of eyelid and orbital xanthogranuloma in adults. METHODS: The authors
      performed a retrospective chart review of 6 patients receiving local
      triamcinolone acetonide (40 mg/ml) injections for the treatment of eyelid and
      orbital xanthogranuloma at the University of Michigan. All patients underwent
      diagnostic biopsy before treatment. The effects of this therapy on symptoms and
      signs of the disease were assessed. RESULTS: All 6 patients had eyelid swelling
      or nodularity and 5 had yellow discoloration of their eyelids. All lesions
      involved the eyelids and anterior orbit and 5 were present bilaterally. Biopsy
      revealed necrobiotic xanthogranuloma in 4 patients and adult-onset
      xanthogranuloma in 2 patients. Triamcinolone acetonide was administered
      intralesionally as series of 2 to 25 injections. Local control was obtained in
      all 6 cases, with the reduction of symptoms and signs of the disease in 5 cases.
      Two patients with necrobiotic xanthogranuloma had development of non-Hodgkin
      lymphoma. Average follow-up of patients whose treatment was not truncated by
      systemic chemotherapy was 52 months (range, 30 to 86 months). No complications
      occurred as a result of this treatment. CONCLUSIONS: Intralesional injection of
      triamcinolone acetonide is an effective, safe treatment for orbital
      xanthogranuloma in adults. This modality avoids the side effects associated with
      systemic corticosteroid or cytotoxic agent therapy.

PMID- 16418664
TI  - Mersilene mesh versus sclera in wrapping hydroxyapatite orbital implants.
AB  - PURPOSE: To compare Mersilene mesh versus sclera in wrapping hydroxyapatite
      orbital implants used in primary enucleation. METHODS: In a prospective,
      randomized, interventional comparative case series, 60 eyes from 60 consecutive
      patients were included and randomly allocated for primary enucleation and either
      Mersilene mesh-wrapped hydroxyapatite (MHA) orbital implant (30 cases, 50%) or
      sclera-wrapped hydroxyapatite (SHA) orbital implant (30 cases, 50%) under general
      anesthesia. Complete socket examination was performed at 1 week, 1 month, and
      then every 3 months after surgery. RESULTS: Mean age was not significantly
      different (P = 0.08) between patients with MHA (36.43 years) and SHA (28.50
      years) orbital implants. The most common cause of enucleation was trauma in both
      groups (P = 0.09). Patients with MHA had significantly (P = 0.005) longer follow
      up time (mean, 11.40 months) than those with SHA (mean, 9.40 months). No exposure
      was found at last follow-up in the MHA group, but one patient in the SHA group
      had a small exposure (1 x 1 mm) 1 month after surgery that was conservatively
      treated. There were no significant postoperative soft tissue complications in
      either group. CONCLUSIONS: Sclera and Mersilene mesh could be used as a wrapping
      material for hydroxyapatite orbital implants without significant complications.
      Absence of disease transmission, low cost, and availability are the main
      advantages of Mersilene mesh.

PMID- 16418665
TI  - A novel approach to re-pegging hydroxyapatite implants using bioactive glass.
AB  - PURPOSE: To determine if bioactive glass, originally designed for
      craniomaxillofacial use, can be used effectively for re-pegging of hydroxyapatite
      orbital implants. METHODS: Over a 2-year period, 3 patients with pegged
      hydroxyapatite orbital implants and related complications that did not respond to
      conservative treatment, underwent removal of the implant pegs and/or sleeves. Peg
      tracts were subsequently filled with bioactive glass. RESULTS: No complications
      occurred in any case during 3 years of follow-up. After 2 months, 2 patients
      underwent successful re-drilling of the peg site and insertion of titanium pegs.
      Both patients were satisfied with the results. The third patient has deferred re
      pegging at this time. CONCLUSION: Bioactive glass is effective for refilling old
      peg tracts and allowing timely re-pegging of hydroxyapatite implants.

PMID- 16418666
TI  - Adverse reactions to permanent eyeliner tattoo.
AB  - PURPOSE: To report the potential for serious adverse reactions associated with
      permanent eyeliner tattoos. METHODS: An observational case series was conducted
      on 4 patients who presented with inflammatory eyelid reactions after receiving
      permanent eyeliner tattoo. RESULTS: Clinically, the tattoo-associated lesions
      were typically firm, raised masses underlying the areas of pigmentation.
      Histopathologic analysis of tissue from all 4 patients demonstrated a
      granulomatous inflammatory response with negative cultures for any organisms.
      Treatment approaches varied between a combination of topical steroid creams,
      local steroid injections, local resection, intramuscular steroid injection, and
      systemic oral steroids. These treatments were successful in all 4 cases.
      CONCLUSIONS: An allergic granulomatous reaction is one of the adverse reactions
      seen after permanent eyeliner tattoo. Treatment can be challenging and may
      ultimately require excision of tattoo pigment to remove the inciting factor.
      Systemic steroids may aid in controlling the inflammation associated with
      reaction to the tattoo pigment.

PMID- 16418667
TI  - Blue filter discs and nasal endoscopic visualization of fluorescein lacrimal
      drainage.
AB  - For the lacrimal surgeon, fluorescein instilled in the palpebral aperture, and
      combined with the use of blue filters, can assist office assessment of lacrimal
      drainage by nasal endoscopy. The fabrication of a separate blue filter attachment
      for nasal endoscopes, however, is expensive. Inexpensive, heat-stable blue filter
      discs were sourced from a manufacturer of fiberoptic instruments in Sydney,
      Australia. These discs can be made in various sizes suitable for standard battery
      powered, portable nasal endoscopes. The discs were used in the postoperative
      assessment of a patient with lacrimal drainage-related pathology. They were easy
      to use and provided suitable wavelength transmission for improved assessment of
      fluorescein drainage through the lacrimal system.

PMID- 16418668
TI  - Effect of 0.5% apraclonidine on ptosis in Horner syndrome.
AB  - To demonstrate the effect of apraclonidine on anisocoria and ptosis in Horner
      syndrome, one drop of 0.5% apraclonidine was instilled in both eyes of 3 patients
      who presented with acute Horner syndrome, and the effect on ptosis and anisocoria
      was documented. As reported in the literature, one drop of 0.5% apraclonidine
      reverses the anisocoria of Horner syndrome. In addition, 0.5% apraclonidine leads
      to a complete resolution of the ptosis associated with Horner syndrome, a finding
      reported once in the literature. Apraclonidine is a safe and readily available
      alternative to cocaine for the diagnosis of Horner syndrome.

PMID- 16418669
TI  - Recurrent acute lymphoblastic leukemia presenting in the lacrimal gland.
AB  - A 14-year-old girl with a history of acute lymphoblastic leukemia presented with
      periorbital swelling of the right eyelid associated with enlargement of the
      lacrimal gland and cervical lymphadenopathy. Radiographic imaging showed diffuse
      enlargement and enhancement of the right lacrimal gland. The patient underwent an
      incisional biopsy of the lacrimal gland that showed atypical lymphocytes
      consistent with recurrent acute lymphoblastic leukemia. The lacrimal gland is a
      rare extramedullary site for recurrence of this disease.

PMID- 16418670
TI  - Schwartz-Jampel syndrome: surgical management of the myotonia-induced
      blepharospasm and acquired ptosis after failure with botulinum toxin A
      injections.
AB  - A 6-year-old boy with Schwartz-Jampel syndrome and severe myotonia-induced
      blepharospasm and ptosis did not respond to botulinum toxin A injections in the
      orbicularis muscle. The clinical diagnosis was further supported by
      electromyography. Surgical management using a combination of techniques in one
      operation produced a satisfactory result for both function and appearance. Muscle
      biopsy was also done during surgery.

PMID- 16418671
TI  - Lower eyelid entropion in Langer-Giedion syndrome.
AB  - Langer-Giedion syndrome results from a genetic deletion on chromosome 8. Although
      redundant skin is part of Langer-Giedion syndrome, lower eyelid entropion and
      eyelid laxity have not been previously reported in the medical literature. We
      report a case of bilateral lower eyelid entropion in a patient with Langer
      Giedion syndrome who successfully underwent entropion repair with anterior
      lamellar resection, lower eyelid retractor advancement, and lateral canthopexy.
      Although she has done well 6 months after surgery, we anticipate that laxity and
      eyelid instability will continue to develop with age, and additional
      reconstructive surgery may be required.

PMID- 16418672
TI  - Association between Erdheim-Chester disease, Hashimoto thyroiditis, and familial
      thrombocytopenia.
AB  - A 28-year-old woman presented with progressive proptosis of the left eye. She had
      a history of familial thrombocytopenia and Hashimoto thyroiditis. CT of the
      orbits demonstrated a bilateral diffuse intraconal and extraconal infiltration.
      Biopsy from the left intraconal area revealed the typical histopathology of
      xanthogranuloma with a mixture of foamy histiocytes, Touton giant cells, and
      eosinophils. Systemic examination revealed a mediastinal and retroperitoneal
      infiltration with a focal lesion in the left kidney. A biopsy of the
      retroperitoneal area showed histopathology identical to that of the orbital
      lesion. A review of the literature indicated that the association between non
      Langerhans histocytoses and immunologic dysfunctions is not uncommon. We
      hypothesize that Erdheim-Chester disease may be linked to an abnormal interaction
      between T-lymphocytes and macrophages similarly to the macrophage activation
      syndromes.

PMID- 16418673
TI  - Angiosarcoma metastatic to the orbit.
AB  - A 61-year-old woman developed metastatic angiosarcoma in her left orbit.
      Diagnosis was confirmed with an incisional orbital biopsy and special markers.
      Treatment and palliation involved the use of multiple cycles of paclitaxcel,
      doxorubicin, and ifosfamide along with adjuvant radiotherapy. The measured
      outcome was tumor mass reduction and mortality. Angiosarcoma was confirmed with
      histologic analysis. The patient responded to the chemotherapy with reduction of
      the tumor mass. However, the disease progressed off the medications. She finally
      died. However, she survived longer than the patient in the only other similar
      case report. Chemotherapy may be a useful palliative adjunct in the control of
      metastatic orbital angiosarcoma. Chemotherapy is unlikely to be curative but
      useful and an adjunct to surgery and radiation therapy.

PMID- 16418674
TI  - Correction of congenital blepharoptosis in oculomotor-abducens synkinesis.
AB  - A 4-year-old boy was referred for blepharoptosis. Examination revealed the
      presence of oculomotor-abducens synkinesis (right upper eyelid elevation with
      right gaze). Reports of congenital oculomotor-abducens synkinesis syndromes are
      rare. Two surgeries required more levator resection than anticipated to obtain
      the first, to our knowledge, reported successful result in this condition.

PMID- 16418675
TI  - Infected aluminum oxide orbital implant.
AB  - Porous orbital implant infection is rare. The diagnosis may be delayed as the
      initial symptoms and signs are not always indicative of implant infection. It is
      often only with time, a persistence of symptoms and signs, and additional
      symptoms and signs that implant infection is suspected.

PMID- 16418677
TI  - Cicatricial conjunctival inflammation with trichiasis as the presenting feature
      of Wegener granulomatosis.
AB  - Wegener granulomatosis has a variety of uncommon initial presentations. Although
      conjunctival involvement in this condition is rare, the diagnosis of Wegener
      granulomatosis should be suspected when the conjunctival inflammation is
      recurrent and not typical of other conjunctival inflammatory conditions.

PMID- 16418676
TI  - Syringocystadenoma papilliferum of the eyelid in a young girl.
AB  - An 8-year-old girl presented with a papillomatous lower eyelid lesion, which had
      been present since infancy. An incisional biopsy diagnosed syringocystadenoma
      papilliferum. The origin and natural history of syringocystadenoma papilliferum
      remain disputed and are reviewed. In view of its association with basal cell
      carcinoma, further management options are discussed.

PMID- 16418679
TI  - Eyelid ptosis associated with an undetected foreign body and a remote entrance
      wound.
AB  - A 12-year-old girl presented with ptosis 10 days after falling onto glass that
      penetrated the frontotemporal region. The immediate ptosis and palpable mass was
      attributed to an undetected foreign body. CT demonstrated a radiopaque foreign
      body. During surgery, the foreign body removed was found to be a piece of glass
      from a soda bottle. The ptosis resolved completely within the next 2 weeks. A
      retained foreign body should be considered in any case of prolonged ptosis after
      penetrating ocular trauma, even when the entrance wound is remote.

PMID- 16418678
TI  - Rapid development of amputation neuroma following excision of an orbital
      cavernous hemangioma.
AB  - A 48-year-old man with left proptosis and signs of optic nerve compression
      underwent medial transconjunctival orbitotomy for an excisional biopsy of a
      posteromedial orbital cavernous hemangioma. The left eye once again became
      proptotic and painful only 5 weeks later because of a more anteriorly growing
      orbital mass, which was homogeneously hyperintense relative to orbital fat on
      both T1- and T2-weighted MRI studies. The tumor proved to be an amputation
      neuroma after total excision. The latter tumor is presumed to originate most
      probably from the transected branch of the oculomotor nerve innervating the
      medial rectus muscle, which remained paralytic after the first operation.

PMID- 16418682
TI  - A new indication for therapeutic drug monitoring in the neonate.

PMID- 16418680
TI  - Retained intra-orbital shotgun cartridge.
AB  - A 45-year-old man under the influence of alcohol sustained a gunshot wound to the
      right eye. The mechanism of the trauma was unclear. Radiography revealed the
      image of a shotgun cartridge in the right orbit. The patient underwent surgical
      removal of the foreign body and enucleation of the right eye.

PMID- 16418683
TI  - Citalopram serum and milk levels in mother and infant during lactation.
AB  - We present a case of intensified therapeutic drug monitoring (TDM) of citalopram
      in mother and newborn infant after clinically observed selective serotonin
      reuptake inhibitor (SSRI)-associated symptoms 2 weeks until 2 months after
      delivery. The SSRI-associated symptoms observed in the infant (up to 3 weeks
      after delivery) were irregular breathing, sleep disorders, hypotonia, and
      hypertonia. We conclude that the SSRI-associated symptoms in the infant represent
      citalopram withdrawal effects rather than side effects caused by breastfeeding.
      This case illustrates the importance of a flexible TDM program and a
      multidisciplinary approach in a hospital setting to deal with cases of drug
      associated adverse effects, such as SSRI withdrawal effects.

PMID- 16418684
TI  - Paroxetine toxicity in a newborn after in utero exposure: clinical symptoms
      correlate with serum levels.
AB  - There are several case reports and case series that have examined the acute
      effects of selective serotonin reuptake inhibitors (SSRIs) on the newborn. There
      is considerable controversy whether the reported symptoms represent withdrawal
      from the SSRI or toxicity caused by the SSRI. A case of an infant who was exposed
      to paroxetine during pregnancy is presented. This case supports the notion of
      serotonin toxicity and is believed to be the first report that substantiates
      clinical symptoms with serum levels of the offending SSRI.

PMID- 16418685
TI  - Thyroid function testing in pregnancy and thyroid disease: trimester-specific
      reference intervals.
AB  - During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid
      hormone concentrations. Accurate assessment of thyroid function during pregnancy
      is critical, for both the initiation of thyroid hormone therapy, and for the
      adjustment of thyroid hormone dose in those already receiving thyroid hormone.
      Trimester-specific intervals are especially important during pregnancy when
      thyroid insufficiency may be associated with adverse obstetric outcome and fetal
      neurodevelopmental deficits. Gestational age-specific reference intervals are now
      available for thyroid function tests. Knowing the expected normal changes in
      hormone concentrations throughout pregnancy allows individualized supplementation
      when necessary.

PMID- 16418686
TI  - Therapeutic drug monitoring of antithyroid drugs in pregnancy: the knowledge
      gaps.
AB  - Despite being a common condition in pregnancy, and despite propylthiouracil (PTU)
      being perceived as safer than methimazole, there are virtually no epidemiological
      controlled studies on malformation rate an neurobehavioral outcomes with the
      former. This knowledge gap must be filled to ensure fetal safety.

PMID- 16418687
TI  - Mechanisms of chronic allograft dysfunction.
AB  - This review was designed to highlight new findings that have contributed to our
      knowledge of the pathogenesis of late graft dysfunction. Both immune and
      nonimmune causes contribute to its development. Specific contributors to late
      graft dysfunction have been recently recognized and are potential targets for new
      treatment options. The variables associated with late graft failure include donor
      age and tissue quality, brain death and other issues specific to the deceased
      donor, tissue injury secondary to organ preservation, alloimmune-mediated injury,
      and posttransplantation factors in the recipient, such as viral infections,
      hypertension, drug toxicity, and hyperlipidemia. One of the critical variables
      that is controllable is the total ischemic time; the longer the ischemic episode,
      the worse the long-term results of the transplant are. Another significant
      obstacle to long-term allograft survival is the MHC barrier. The roles of B cells
      and alloantibody as effectors of alloimmunity have been underestimated; emerging
      studies strongly suggest that previous sensitization and/or de novo donor-anti
      human lymphocyte antigen (HLA) antibodies secondary to poor HLA matching portend
      a poor prognosis for allograft survival, even in the presence of chronic T-cell
      specific immunosuppression.

PMID- 16418688
TI  - Proteomic research in renal transplantation.
AB  - Expression proteomics is a valuable tool for biomarker discovery. Currently there
      is a great deal of interest in the development of urine biomarkers for detection
      of renal allograft rejection as an alternative to percutaneous needle biopsy,
      which is the "gold standard." Needle biopsy is costly and associated with
      significant patient morbidity and mortality. This review will discuss the
      author's current work in proteomics-based urine biomarker discovery, as well as
      alternative approaches used by other groups that use SELDI mass spectrometry. The
      current state of urine transplant biomarkers will be discussed, and in conclusion
      there will be a brief discussion of how urine biomarkers will be used for
      transplant patient management once they are validated and analyte-specific assays
      are developed.

PMID- 16418689
TI  - Pharmacogenetics in transplant patients: can it predict pharmacokinetics and
      pharmacodynamics?
AB  - Pharmacogenetics holds the potential to allow individualized dosing of
      immunosuppressive agents to optimize their therapeutic effect while minimizing
      adverse effects. As more pharmacogenetic information accumulates, the prospect of
      reducing or discontinuing the intensive therapeutic drug monitoring of
      immunosuppressants looks attractive. However, the long process of developing
      useful clinical information from basic information on the genes of interest is at
      a very early stage, and our present information does not supercede
      pharmacokinetic or blood concentration monitoring of immunosuppressants. The most
      extensive blood concentration/dose information available is on tacrolimus and its
      dosing related to CYP3A5 and ABCB1 gene polymorphisms. Although CYP3A5 genotype
      is definitely associated with tacrolimus dosing, the only recommendation
      presently published is for an arbitrary doubling of the starting tacrolimus dose
      in CYP3A5 expressors. For cyclosporine, sirolimus, and corticosteroids, the
      presently available pharmacogenetic information does not permit pharmacokinetic
      predictions. The pharmacodynamics of immunosuppressants, as evidenced by effects
      on acute rejection or adverse drug effects, have considerably more potential for
      prediction by pharmacogenetic models. Drug-resistant rejection, nephrotoxicity,
      steroid resistance and osteonecrosis, and even patient survival may ultimately be
      predicted by models incorporating multiple gene polymorphisms and other critical
      patient information. At this point, treatment algorithms can be developed that
      will allow us to individualize a transplant patient's immunosuppressive therapy.

PMID- 16418690
TI  - Within-patient variability of mycophenolic acid exposure: therapeutic drug
      monitoring from a clinical point of view.
AB  - Exposure to mycophenolic acid (MPA) is highly variable among patients on standard
      dose mycophenolate mofetil (MMF) therapy. In addition, MPA exposure increases
      with time posttransplant and exposure is predictive for the development of acute
      rejection. Consequently, therapeutic drug monitoring (TDM) of MPA may improve
      clinical outcome, although a large within-patient variability could be a
      limitation. This study was designed to analyze the extent of within-patient
      variability of MPA exposure for area-under-the-curve (AUC0-12) and pre-dose
      concentrations (C0). For 9 occasions during the first 5 months after
      transplantation, AUC0-12 and C0 values from 45 renal transplant recipients, all
      using cyclosporine and corticosteroids, were divided into quartiles. When AUC0-12
      or C0 changed 1, 2, or 3 quartiles within a patient from one occasion to the
      next, a score of respectively 1, 2, or 3 points was assigned. Doing this for all
      8 between occasion intervals, the maximal score for within-patient variability
      could be 8 x 3 = 24 per patient. For AUC0-12, the median overall score was 3.4 of
      maximal 24. For C0 measurements, this score was significantly higher: 6.0 (P <
      0.001). The higher overall score for C0 was explained by more quartile changes
      during the first weeks after transplantation. It is concluded that within-patient
      variability for MPA exposure is low in kidney transplant recipients during the
      first 5 months after transplantation. In the first weeks after transplantation,
      within-patient variability is larger for C0 than for AUC0-12.

PMID- 16418691
TI  - Biomarkers: the link between therapeutic drug monitoring and pharmacodynamics.

PMID- 16418692
TI  - Active drug transport of immunosuppressants: new insights for pharmacokinetics
      and pharmacodynamics.
AB  - Immunosuppressants have a narrow therapeutic index, and pharmacokinetic
      variability negatively affects long-term outcome of transplantation. Recently, it
      has become clear that active transport is a major determinant of the inter-and
      intraindividual variability of the pharmacokinetics and pharmacodynamics of
      immunosuppressants. Active transport plays a key role in (1) the poor correlation
      between oral doses and systemic exposure of cyclosporine, tacrolimus, sirolimus,
      and everolimus, (2) tissue distribution including distribution into lymphocytes,
      (3) hepatic and intestinal metabolism, (4) the pharmacokinetic variability of
      immunosuppressants after oral dosing, (5) drug-drug interactions, (6) disease
      drug interactions, and (7) age, gender, and ethnicity-based differences in
      pharmacokinetics of immunosuppressants. Those new insights may significantly
      improve patient management and long-term outcome not only by reducing
      pharmacokinetic variability and avoidance of drug-drug interactions but also by
      identification of sensitive patient populations. They will also significantly
      impact preclinical and clinical development strategies of new immunosuppressants.

PMID- 16418693
TI  - Pharmacokinetics of 6-thioguanine in patients with inflammatory bowel disease.
AB  - 6-Thioguanine (6-TG) seems to be an attractive alternative in both AZA- and 6-MP
      intolerant and -resistant IBD populations. However, little is known of 6-TG
      pharmacokinetics, metabolite levels, and their correlation with drug efficacy and
      toxicity in IBD patients. This study reports the 6-TG pharmacokinetics in a
      population of IBD patients and the predictive value of metabolite concentrations.
      Red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) concentrations were
      measured in 28 IBD patients at t = 1, 2, 4, and 8 weeks after starting 6-TG, 20
      mg once daily. Outcome measures included mean 6-TGN concentrations (+/-95%
      confidence interval [CI95%]) and their associations with TPMT genotype, 6-TG
      dose, and hematological, hepatic, pancreatic, and efficacy parameters during the
      8 week period. Steady-state 6-TGN concentrations were reached after 4 weeks,
      indicating a half-life of approximately 5 days, and measured 856 (CI95% 715-997)
      pmol/8 x 10 RBCs. Large interpatient variability occurred at all time-points. No
      correlation was found between steady-state 6-TGN concentrations and drug dose per
      kilogram body weight. No significant differences in 6-TGN concentrations were
      found between patients with adverse events and patients without any event. Also,
      mean 6-TGN concentrations did not differ in patients with active disease versus
      patients in remission. In IBD patients on 6-TG treatment, large interindividual
      differences in metabolite concentrations occur. In our population, we could not
      demonstrate a clear relationship between 6-TGN concentrations on one hand and
      toxicity and efficacy on the other, as exist in AZA- and 6-MP-treated patients.

PMID- 16418694
TI  - Pharmacokinetics and metabolic disposition of sirolimus in healthy male
      volunteers after a single oral dose.
AB  - The pharmacokinetics and metabolic disposition of sirolimus (rapamycin,
      Rapamune), a macrocyclic immunosuppressive agent for the prevention of allograft
      rejection in organ transplantation, were investigated in 6 healthy male
      volunteers after a single nominal 40-mg oral dose of the C-radiolabeled drug,
      with the added aim of assessing the potential role of sirolimus metabolites in
      the clinical pharmacology of the parent drug. The absorption of parent drug and
      derived materials was rapid (tmax 1.3 +/- 0.5 hours, mean +/- SD), and the
      elimination of sirolimus was slow (t(1/2) 60 +/- 10 hours, mean +/- SD) in whole
      blood. The high whole blood to plasma (B/P) concentration ratio of sirolimus (142
      +/- 39) was consistent with its extensive partitioning into formed blood
      elements. The markedly lower B/P value based on radioactivity (2.7 +/- 0.4)
      suggested that drug-derived products partitioned into formed blood elements to a
      much lesser extent. Based on AUC0-144h values, unchanged sirolimus represented an
      average 35% of total radioactivity in whole blood. Drug-derived products in whole
      blood were characterized by HPLC, LC/MS, and LC/MS/MS as 41-O-demethyl, 7-O
      demethyl, and several hydroxy, dihydroxy, hydroxy-demethyl and didemethyl
      sirolimus metabolites. The percentage distribution of sirolimus metabolites in
      whole blood ranged from 3%-10% at 1 hour to 6%-17% at 24 hours after drug
      administration. Based on their low immunosuppressive activities and relative
      abundance in whole blood of humans after sirolimus administration, metabolites of
      sirolimus do not appear to play a major role in the clinical pharmacology of the
      parent drug. A majority of the administered radioactivity (91.0 +/- 8.0%) was
      recovered from feces, and only 2.2% +/- 0.9% was renally excreted.

PMID- 16418695
TI  - Development of a pharmacokinetic and Bayesian optimal sampling model for
      individualization of oral busulfan in hematopoietic stem cell transplantation.
AB  - Therapeutic drug monitoring is used to minimize toxicity and maximize the
      therapeutic efficacy of busulfan, which shows high intra- and interpatient
      pharmacokinetic variability and erratic oral absorption. This study was designed
      to develop a pharmacokinetic model that could accommodate the erratic oral
      absorption of busulfan and to use this model to develop an optimal sparse
      pharmacokinetic sampling strategy to improve the precision and efficiency of
      therapeutic drug monitoring. Twenty-one pharmacokinetic profiles were collected
      from 12 patients receiving oral busulfan before hematopoietic stem cell
      transplantation. Each pharmacokinetic profile was defined by 5 to 9 plasma
      concentrations. Candidate pharmacokinetic models were initially fit to the data
      by maximum likelihood, with model discrimination by Akaike's Information
      Criterion. Maximum likelihood results were used to derive Bayesian previous
      parameter estimates, and D-optimal design was used to determine optimal sparse
      sampling strategies. Each candidate sampling strategy was tested in each patient
      by comparing the resultant Css obtained from the sparse strategy to the actual
      Css derived from each patient's full pharmacokinetic dataset. The final model was
      a 1-compartment model, with oral busulfan absorbed in 1 to 3 phases, and fit the
      data well. All limited sampling models tested were unbiased in their results, and
      a 4-sample scheme proved to adequately characterize busulfan pharmacokinetics,
      and should allow for a reduced sampling frequency for therapeutic drug
      monitoring.

PMID- 16418696
TI  - Population pharmacokinetics of metformin in late pregnancy.
AB  - The pharmacokinetic disposition of metformin in late pregnancy was studied
      together with the level of fetal exposure at birth. Blood samples were obtained
      in the third trimester of pregnancy from women with gestational diabetes or type
      2 diabetes; 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood
      sample also was obtained at the delivery of some of these women, and also at
      delivery of others who had been taking metformin during pregnancy but from whom
      no blood had been taken. Plasma metformin concentrations were assayed by a new,
      validated, reverse-phase HPLC method. A 2-compartment, extravascular maternal
      model with transplacental partitioning of drug to a fetal compartment was fitted
      to the data. Nonlinear mixed-effects modeling was performed in NONMEM using FOCE
      with INTERACTION. Variability was estimated using logarithmic interindividual and
      additive residual variance models; the covariance between clearance and volume
      was modeled simultaneously. Mean (range) metformin concentrations in cord plasma
      and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0.1-2.9)
      mg/L, respectively. Typical population values (interindividual variability, CV%)
      for allometrically scaled maternal clearance and volume of distribution were 28
      L/h/70 kg (17.1%) and 190 L/70 kg (46.3%), giving a derived population-wide half
      life of 5.1 hours. The placental partition coefficient for metformin was 1.07
      (36.3%). Neither maternal age nor weight significantly influenced the
      pharmacokinetics. The variability (SD) of observed concentrations about model
      predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to
      those in nonpregnant patients and, therefore, no dosage adjustment is warranted.
      Metformin readily crosses the placenta, exposing the fetus to concentrations
      approaching those in the maternal circulation. The sequelae to such exposure, eg,
      effects on neonatal obesity and insulin resistance, remain unknown.

PMID- 16418697
TI  - Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone.
AB  - Perospirone is an atypical antipsychotic agent originated and clinically used in
      Japan. Based on an in vitro study, it is reported that perospirone is mainly
      metabolized to ID-15036 by cytochrome P450 (CYP) 3A4. In this study, the authors
      investigated the effects of itraconazole, which is a specific inhibitor of
      CYP3A4, or tandospirone, which is mainly metabolized by CYP3A4 and is expected to
      competitively inhibit the activity of this enzyme, on single oral dose
      pharmacokinetics of perospirone. After pretreatment with 200 mg daily of
      itraconazole or 10 mg daily of tandospirone for 5 days, 9 healthy male subjects
      received 8 mg of perospirone. Plasma concentrations of perospirone and ID-15036
      up to 10 hours after perospirone dosing were measured by high-performance liquid
      chromatography (HPLC). The metabolism of perospirone was significantly inhibited
      by treatment with itraconazole but not by tandospirone. The present study
      suggests that CYP3A4 is significantly involved in metabolism of perospirone in
      humans.

PMID- 16418698
TI  - Pharmacokinetics of amrubicin and its active metabolite amrubicinol in lung
      cancer patients.
AB  - Amrubicin, a synthetic 9-aminoanthracycline agent, was recently approved in Japan
      for treatment of small-cell lung cancer and non-small-cell lung cancer. Amrubicin
      is converted enzymatically to the C-13 hydroxy metabolite amrubicinol, which is
      active and possesses a cytotoxicity 10 to 100 times that of the parent drug. The
      purpose of this study was to characterize the pharmacokinetics of amrubicin and
      its active metabolite amrubicinol. Amrubicin was administered on days 1-3 in 16
      patients with advanced lung cancer. The pharmacokinetics analysis of amrubicin
      and amrubicinol was performed by high-performance liquid chromatography. When 45
      mg/m amrubicin was administered in a bolus injection once every 24 hours for 3
      consecutive days, the areas under the curves (0 to 72 hours) for amrubicin and
      amrubicinol were 13,490 and 2585 ng . h/mL, respectively. The apparent total
      clearance (CLapp) of amrubicin was 15.4 L/h. The area-under-the-curve ratio of
      amrubicinol to amrubicin was 15.1 +/- 4.6% (mean +/- SD) at doses ranging from 30
      to 45 mg/m. Interindividual variability in the enzymatic conversion of amrubicin
      to amrubicinol was small. In contrast, a large interindividual variability in the
      CLapp of amrubicin was observed (CV = 49.8%). The areas under the curves of
      amrubicin and amrubicinol seemed to be associated with the severity of
      hematologic toxicities. There is a possibility that monitoring of the plasma
      concentrations of amrubicin and amrubicinol may provide an efficient tool for
      establishing the optimal dosage of amrubicin in each patient.

PMID- 16418699
TI  - Appropriateness of therapeutic drug monitoring for antidepressants in routine
      psychiatric inpatient care.
AB  - Although there is sufficient evidence of the benefits of therapeutic drug
      monitoring (TDM) for optimizing antidepressant therapy, its current use in
      routine care is far from optimal. As a prerequisite for developing improvement
      strategies, the appropriateness of TDM use was investigated in a psychiatric
      hospital in which TDM is applied routinely to a large extent. A retrospective
      analysis of all patients admitted in 2003 with a unipolar depressive disorder was
      performed. Based on detailed chart review, for all TDM tests, the time of blood
      sample taking in relation to the medication process and the consequences of the
      TDM results for clinical decision making were analyzed. Altogether, 748 plasma
      levels were measured for antidepressants. The evaluation identified considerable
      inappropriate use of TDM. After a preceding change of dose, only the minority of
      TDM tests was performed within an optimum time interval. Overall, 30% of blood
      samples were taken too early, before steady state had been reached. The high
      number of repeat tests without preceding change of drug dose points to
      potentially redundant use. There also was evidence of underuse of TDM, as in many
      cases additional plasma level determinations might have been useful to speed up
      optimal dosing. Frequent discrepancies were found between the laboratory's
      recommendations and actual clinical decision making. Suggested dose changes were
      followed in only 30%. The findings clearly indicate the need for measures to
      improve the implementation of TDM in routine care. Based on the identified
      pattern of current TDM utilization and experiences from other fields of medicine,
      a combination of strategies, including both educational and electronic
      interventions, may have the greatest potential for improvement.

PMID- 16418700
TI  - Determination of amprenavir total and unbound concentrations in plasma by high
      performance liquid chromatography and ultrafiltration.
AB  - Amprenavir is an HIV-1 protease inhibitor with high protein binding (90%) in
      human plasma. This study was designed to develop an assay to measure the
      concentration of unbound amprenavir, to study variation with time in patients,
      and to investigate whether ritonavir and lopinavir, other protease inhibitors
      that could be combined, interact with amprenavir protein binding in vitro. A
      reverse-phase high-performance liquid chromatography assay to UV detection was
      developed and validated to measure total amprenavir in plasma, and this method
      was adapted to quantitate low concentrations of unbound amprenavir in
      ultrafiltrate aqueous fluid. Equilibrium dialysis and ultrafiltration were used
      and compared with separate unbound fraction. The latter method was easier to use
      and was, therefore, subsequently adopted. In 10 patients who received amprenavir
      600 mg bid combined with ritonavir, mean amprenavir free-fraction in plasma was
      8.6% (range, 4.4-20%). When added to pooled human plasmas at concentrations close
      to those found in treated patients, the unbound amprenavir fraction was increased
      in the presence of lopinavir, but remained unaffected by ritonavir. It remains to
      be seen whether measurement of unbound concentrations, rather than total
      concentrations, could improve therapeutic drug monitoring.

PMID- 16418701
TI  - Pharmacokinetics of mycophenolic acid and metabolites in diabetic kidney
      transplant recipients.
AB  - Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is an
      immunosuppressive agent commonly used after organ transplantation. Because
      diabetes mellitus may affect disposition of pharmacologic agents, we investigated
      the influence of diabetes on the pharmacokinetics of MPA, unbound MPA (fMPA) and
      its phenyl and acyl glucuronide metabolites (MPAG and AcMPAG respectively). The
      study included 13 diabetic and 11 nondiabetic, stable, kidney-transplant
      recipients who were receiving a triple maintenance immunosuppressive regimen.
      Serial plasma samples were obtained predose and at regular intervals for 12
      hours. Gastric emptying was assessed using an acetaminophen absorption test and
      glomerular filtration rate was estimated using iohexol clearance. Treatment
      groups were well matched. The time to maximum concentration (Tmax) of MPA was
      86.4 +/- 41.4 minutes versus 52.8 +/- 31.8 minutes in D and ND patients
      respectively (P = 0.04) indicating a delay in MMF absorption. Neither the maximum
      MPA concentration nor the 0- to 12-hour area under the concentration-time curve
      were different. All parameters derived for fMPA and the MPA metabolites were
      comparable between the 2 groups, except for the metabolite ratio of MPAG and
      AcMPAG, which was higher for diabetic patients (P = 0.03). Delayed gastric
      emptying seemed to have reduced the initial rate but not the extent of MPA
      absorption in diabetic patients. The profiles of fMPA were similar in both
      patient groups. With the exception of metabolite concentration ratio, none of the
      other parameters associated with MPA metabolism were different between the 2
      groups.

PMID- 16418702
TI  - Heterozygous mutation in CYP2C19 significantly increases the concentration/dose
      ratio of racemic citalopram and escitalopram (S-citalopram).
AB  - There is limited documentation of the importance of heterozygous cytochrome P450
      (CYP) mutations on drug exposure. This study was designed to evaluate the
      influence of heterozygous mutations in CYP2C19 on the serum concentration of
      racemic citalopram and escitalopram (S-citalopram). Eighty-three samples from
      subjects with determined CYP2C19 and CYP2D6 genotype receiving racemic citalopram
      or S-citalopram as part of their clinical treatment were collected from a routine
      therapeutic drug monitoring database. Concentration/dose (C/D) ratios, parent
      drug/metabolite ratios, and serum concentrations in CYP2C19 homozygous extensive
      metabolizers (EMs) and heterozygous extensive metabolizers (HEMs) were compared.
      The median C/D ratio was significantly higher in the HEM group compared with the
      EM group, both for racemic citalopram (8.0 vs. 4.9, P < 0.01) and S-citalopram
      (5.3 vs. 2.6, P < 0.01). The median parent drug/metabolite ratio was
      significantly higher in the HEM group compared with the EM group, both for
      racemic citalopram (2.9 vs. 1.6, P < 0.01) and for S-citalopram (2.4 vs. 1.2, P <
      0.01). A higher median non-dose-corrected serum concentration also was observed
      in HEMs compared with EMs both for S-citalopram (P < 0.01) and racemic citalopram
      (P = 0.066). This study shows that the metabolism of racemic citalopram and S
      citalopram is significantly impaired in CYP2C19 HEMs. Higher absolute serum
      concentrations indicate that this is not compensated for by dose reductions in
      clinical practice.

PMID- 16418703
TI  - Assessment of chronic exposure to MDMA in a group of consumers by segmental hair
      analysis.
AB  - The suitability of segmental hair analysis of MDMA to monitor past chronic
      exposure to the drug was investigated in a follow-up study of ecstasy consumers.
      The purpose, among others, was to look for an objective biomarker of the history
      of drug consumption. Thirteen naturally colored hair samples were used to assess
      possible association between hair concentration of MDMA in 1-, 5-, and 9-cm
      segments and self-reported use in the last 1, 6, and 12 months. Agreement between
      the self-reported data given by the subjects on their "ecstasy" use in the
      previous month and MDMA hair concentration was good (r = 0.92) in all the
      examined subjects, with the exception of 2 individuals who declared a high
      consumption of the drug (12 tablets in the last month). When comparing the
      subjects' declaration of tablets consumed per month within the last 6 months,
      concordance with the hair MDMA values decreased and no correlation seemed to
      exist between the mean number of tablets consumed in the last 12 months and the
      concentration of MDMA in hair. However, when grouping subjects with a similar
      level of declared drug use (independently of whether in the previous month, last
      6 months and last 12 months) and comparing the data with the mean MDMA
      concentrations found in the corresponding hair segments, an excellent level of
      agreement was found in groups of subjects consuming <5 tablets of MDMA per month
      (r = 0.93). Although the present findings were obtained from a small group of
      individuals and are intended as preliminary results, we can conclude that a
      cutoff of 0.5 ng MDMA per mg hair seems reasonable to assess drug consumption,
      unless the level of consumption was once per month in the last 12 months.
      Doubling the monthly consumption increases hair MDMA by around 1 ng/mg hair up to
      a level of 4 consumed tablets a month. It does not seem possible to draw
      definitive conclusions from higher concentrations in hair samples.

PMID- 16418704
TI  - An improved HPLC fluorimetric method for the determination of enfuvirtide plasma
      levels in HIV-infected patients.
AB  - An improved HPLC fluorimetric method for the quantification of enfuvirtide in
      plasma of HIV-infected subjects was described and validated. The use of an
      internal standard improved the reproducibility and precision of the analysis. Our
      method showed lower limits of detection and quantification (LOD = 32 ng/mL, LOQ =
      78 ng/mL), lower intraday (RSD% 1.25-2.95) and interday (RSD% 1.75-4.69)
      coefficients of variation, greater recovery (>100%), lower duration (16 minutes)
      and lower cost than previously described fluorimetric methods. Therefore, this
      method can be used as a reliable tool for pharmacokinetic studies of enfuvirtide.

PMID- 16418705
TI  - High-performance liquid chromatography method for the determination of
      mycophenolic acid and its acyl and phenol glucuronide metabolites in human
      plasma.
AB  - Measuring the concentration of the pharmacologically active metabolite of
      mycophenolic acid (MPA), acyl-MPAG (AcMPAG), in addition to the pharmacologically
      inactive phenol glucuronide metabolite (MPAG) may prove useful in the therapeutic
      drug monitoring of MPA. A simple high-performance liquid chromatography method
      with ultraviolet detection (HPLC-UV) was established for simultaneous
      determination of MPA, AcMPAG, and MPAG in human plasma. The method utilizes 2
      internal standards (IS), phenolphthalein glucuronic acid (PGA) for MPAG and a
      carboxy butoxy derivative of MPA (MPAC) for AcMPAG and MPA. The method consists
      of solid-phase extraction of the analytes followed by analysis over a Zorbax Rx
      C8 column (150 x 4.6 mm, 5 mum) at 254 nm. The analytes were separated with a
      gradient mixture of methanol and 0.1% phosphoric acid over a run time of 14
      minutes at a flow rate of 1 mL/min. The assay was linear in the concentration
      range from 0.2 to 50 mg/L for MPA, 0.5 to 25 mg/L for AcMPAG, and 2 to 500 mg/L
      for MPAG. The mean +/- SD interday accuracy and %CV for MPA were 100.3 +/- 5.7
      and 5.7%, for AcMPAG, 102.6 +/- 5.7 and 5.6%, and for MPAG 100.5 +/- 5.3 and
      5.3%, respectively. The average +/- SD of MPA, MPAG, and AcMPAG maximum
      concentrations (Cmax) in 23 kidney transplant recipients on 500 or 1000 mg twice
      daily mycophenolate mofetil were 11.77 +/- 9.43, 88.15 +/- 46.4, and 3.01 +/-
      1.73 mg/L, respectively, and the predose trough (Cmin morning) concentrations
      were 2.24 +/- 3.11, 55.44 +/- 29.55, and 1.42 +/- 0.74 mg/L, respectively. The
      method described is robust, sensitive, reproducible, and will be useful in
      therapeutic drug monitoring or pharmacokinetic studies of MPA.

PMID- 16418706
TI  - A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry
      technique for monitoring antidepressants in human serum.
AB  - Antidepressants belong to a variety of chemical and pharmacologic classes. Most
      require therapeutic drug monitoring, at least in certain circumstances, such as
      unexplained inefficacy or suspected toxicity. Several types of chromatographic
      methods have generally been used. This paper presents a fully automated,
      sensitive, and specific method for the therapeutic drug monitoring of 13
      antidepressants of all classes (amoxapine, amitriptyline, citalopram,
      clomipramine, dothiepin, doxepin, fluoxetine, imipramine, maprotiline, mianserin,
      paroxetine, sertraline, trimipramine) and some of their respective active
      metabolites (nortriptyline, monodesmethylcitalopram, desmethylclomipramine,
      desipramine, norfluoxetine, desmethylmianserin, N-desmethylsertraline), based on
      the innovative turbulent-flow liquid chromatography (TFC) technology, coupled to
      tandem-mass spectrometry (MS/MS). The antidepressants were divided in two groups
      depending on their chromatographic properties, so that two injections would be
      necessary to screen all compounds (which is infrequent for therapeutic drug
      monitoring). Calibration curves ranged from 10 to 500 ng/mL. No significant
      memory effect was observed after the injection of a blank serum sample spiked at
      500 ng/mL. The intra-assay and inter-assay precision CVs ranged from 0.4% to 12%
      and from 1% to 16%, respectively. The method was further validated by blindly
      analyzing Heathcontrol-Therapeutic Drugs Scheme samples (Cardiff Bioanalytical
      Services Ltd.) containing several antidepressants.

PMID- 16418707
TI  - Rapid quantitative determination of L-FMAU-TP from human peripheral-blood
      mononuclear cells of hepatitis B virus-infected patients treated with L-FMAU by
      ion-pairing, reverse-phase, liquid chromatography/electrospray tandem mass
      spectrometry.
AB  - The purpose of this study was to develop an analytical method for the
      determination of 2'-fluoro-5-methyl-beta-l-arabinofuranosyl uracil triphosphate
      (L-FMAU-TP) in human peripheral blood mononuclear cells (PBMCs), and its
      application in the determination of cellular levels of L-FMAU-TP in PBMCs
      isolated from patients treated with 2'-fluoro-5-methyl-beta-l-arabinofuranosyl
      uracil (L-FMAU). An ion-pairing liquid chromatography (IPC) method, coupled with
      negative ion electrospray ionization tandem mass spectrometry (ESI-MS/MS), was
      developed for the accurate and repeatable detection of L-FMAU-TP, with a limit of
      detection of 1.6 pmol/10 cells. The calibration curve for L-FMAU-TP was linear
      over the concentration range 1.6 to 80 pmol/10(6) cells. The intra- and inter-day
      precision was lower than 11.2%, and the accuracy was between 97.1 and 106.9%.
      When applied to the determination of L-FMAU-TP in PBMCs isolated from HBV
      infected patients undergoing L-FMAU treatment, the levels reached a steady state
      concentration 4 weeks after daily single oral administration of 20 mg L-FMAU, and
      these levels were maintained for up to 12 weeks, but then decreased 12 weeks
      after drug cessation. The terminal half-life of L-FMAU-TP in PBMCs after drug
      cessation was estimated to be 15.6 days.

PMID- 16418708
TI  - Population pharmacokinetics of cyclosporine in cardiopulmonary transplant
      recipients.

PMID- 16418710
TI  - A probable case of amygdalin-induced peripheral neuropathy in a vegetarian with
      vitamin B12 deficiency.

PMID- 16418711
TI  - Defective alleles may not have contributed to adverse effects.

PMID- 16418712
TI  - Defective alleles may not have contributed to adverse effects.

PMID- 16418722
TI  - Increased megakaryocytopoiesis in Lyn-deficient mice.
AB  - Previous studies in cell lines have shown Lyn kinase to be a negative regulator
      of thrombopoietin (TPO)-induced proliferation. To further investigate the role of
      Lyn during megakaryocytopoiesis, Lyn-deficient mice (lyn(-/-)) were analyzed. We
      observed that lyn(-/-) mice have more bone marrow-derived GPIIB (CD41) and Mpl(+)
      cells when compared to their wild-type littermates. In addition, colony-forming
      unit-megakaryocytes (CFU-MK) are increased and TPO-induced expansion of primary
      marrow cells yielded a greater number of mature megakaryocytes (MKs) with
      increased nuclear ploidy. Histopathology of bone marrow and spleens from lyn(-/-)
      mice showed an increase in the number of MKs. Mechanistic studies revealed that
      TPO stimulation of MKs from lyn(-/-) mice did not affect phosphorylation of Janus
      kinase 2 (JAK2), signal transducer and activator of transcription (STAT) 3,
      STAT5, or MAP kinase kinase (MEK). Lyn-deficient MKs supported greater TPO
      mediated phosphorylation and kinase activity of both Erk1/2 (mitogen-activated
      protein kinase, MAPK) and Akt. In contrast, there was a reduction of tyrosine
      phosphorylation of the inositol phosphatase, SHIP. This is the first direct
      evidence using primary MKs from Lyn-deficient mice that confirms our prior data
      from cell lines that Lyn kinase is a negative regulator of TPO signaling.

PMID- 16418723
TI  - C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth
      inhibition of colon cancer cells.
AB  - Changes in carbohydrates on the cell surface are associated with tumor
      malignancy. The mucin-type core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT
      M) is highly expressed in the gastrointestinal tract and catalyses the formation
      of core 2, core 4, and blood group I branches on O-glycans. In the present study,
      we evaluated the role of C2GnT-M in colorectal cancer. C2GnT-M downexpression was
      observed in 73.6% of the primary tumors from colorectal cancer patients (39 of
      53) analysed by cancer profiling array. Consistently, the majority of colon
      cancer cell lines and primary colon tumors expressed lower levels of C2GnT-M than
      did normal colon tissues by RT-PCR. HCT116 cells stably transfected with C2GnT-M
      inhibited expression of the core 1 structure, Galbeta1,3GalNAcalpha1-Ser/Thr, on
      the cell surface. Moreover, C2GnT-M expression suppressed cell adhesion,
      motility, and invasion as well as colony formation ability. The growth of C2GnT-M
      transfected HCT116 and SW480 cells was dramatically suppressed, and the cell
      death induced by C2GnT-M was demonstrated by an increase in the annexin V
      positive cells. Interestingly, C2GnT-M inhibited cell adhesion to collagen IV and
      fibronectin, and decreased tyrosine phosphorylation of paxillin, indicating that
      the changes in cancer behavior may be partly mediated by integrin-signaling
      pathways. Tumor growth in vivo was also significantly suppressed by C2GnT-M in
      the xenografts of nude mice. These results demonstrate that C2GnT-M is frequently
      downregulated in colorectal cancer and suppresses colon cancer cell growth.

PMID- 16418724
TI  - RET ligand-induced internalization and its consequences for downstream signaling.
AB  - RET is a receptor tyrosine kinase (RTK) with roles in cell growth,
      differentiation and survival. Ligand-induced activation of RET results in
      stimulation of multiple signal transduction pathways, including the MAP
      kinase/Erk and PI3 kinase/Akt pathways. However, the mechanisms governing
      receptor internalization and signal down- regulation have not been explored. As
      other RTKs are internalized through the clathrin-coated pit pathway in a ligand
      dependant manner, we have investigated whether RET is internalized through a
      similar process. Using a highly sensitive fluorescence resonance energy transfer
      (FRET)-based assay, we have shown that RET is internalized from the plasma
      membrane in a ligand-dependant manner that requires RET kinase activity as well
      as the GTPase activity of the clathrin-coated vesicle scission protein dynamin 2.
      Further, we have demonstrated that RET colocalizes with Rab5a, a marker of
      clathrin-coated vesicles and early endosomes, after internalization. Finally, we
      demonstrated that RET internalization is required for complete activation of
      Erk1/2, but not for activation of Akt signaling. Our data suggest that ligand
      induced internalization of RET not only plays an overall role in downregulation
      and termination of signaling, but also functions to traffic RET to subcellular
      locations where it can fully activate certain downstream signaling pathways.

PMID- 16418725
TI  - A functionally distinct member of the DP family of E2F subunits.
AB  - E2F transcription factors regulate genes involved in cell-cycle progression. In
      mammalian cells, physiological E2F exists as an E2F/DP heterodimer. Currently,
      eight E2F and two DP subunits have been characterized. We report here the
      characterization of a new member of the DP family, DP-4. While DP-4 exhibits
      certain similarities with members of the DP family, it also possesses a number of
      significant differences. Thus, DP-4 forms a heterodimer with E2F subunits, binds
      to the E2F site and associates with pocket proteins including pRb. In contrast to
      DP-1, however, DP-4/E2F-1 complexes exhibit reduced DNA binding activity.
      Furthermore, DP-4 interferes with E2F-1-dependent transcription and delays cell
      cycle progression. These results highlight an emerging complexity in the DP
      family of E2F subunits, and suggest that DP-4 may endow E2F heterodimers with
      distinct transcription properties.

PMID- 16418727
TI  - How big is the universe?

PMID- 16418726
TI  - Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF
      kappaB activation.
AB  - Human herpesvirus 8 (HHV-8) encodes a viral FLICE inhibitory protein (vFLIP),
      called K13, with homology to the prodomain of caspase 8. K13 has been postulated
      to protect virally infected cells against death receptor-induced apoptosis. We
      report that K13 leads to constitutive upregulation of IL-8 secretion by
      transcriptional upregulation of its promoter. K13-induced IL-8 promoter
      activation is dependent on an intact NF-kappaB-binding site and is associated
      with increased binding of classical NF-kappaB pathway subunits p65, c-Rel and
      p50, respectively. IL-8 production is defective in K13 mutants defective in
      classical NF-kappaB activation and is blocked by genetic and pharmacological
      inhibitors of this pathway. In contrast, K13 failed to activate the JNK/AP-1
      pathway and deletion of AP-1-binding site in the IL-8 promoter or use of a
      specific JNK inhibitor had only a partial effect on K13-induced IL-8 promoter
      activation. Collectively, above results demonstrate that K13 is a major mediator
      of IL-8 production and therapeutic agents targeting K13-induced NF-kappaB pathway
      may have a role in the treatment of conditions in which HHV-8-induced IL-8
      production plays a pathogenic role.

PMID- 16418731
TI  - Microchimerism and skin disease: true-true unrelated?
AB  - Microchimerism, the stable presence of foreign cells in an individual, may result
      from trafficking during pregnancy or from organ or hematopoietic transplantation,
      and has been hypothesized to cause autoimmunity and certain skin diseases. Yet
      microchimeric cells are found in normal individuals and may be important to
      tissue repair. Thus microchimerism may be common, and finding microchimeric cells
      in diseased as well as normal tissue may be a "true-true unrelated" situation.

PMID- 16418732
TI  - (P)PARsing epidermal development.
AB  - Overexpression of PPAR-alpha, a developmental transcription factor important in
      epidermal embryogenesis, in basal keratinocytes causes epidermal thinning when
      activated constitutively during development, but not if activated in adults; and
      lack of PPAR-alpha transiently delays stratum corneum formation within a window
      late in epidermal development (day 18.5 to birth). In contrast, pharmacologic
      activation of PPAR-alpha inhibits proliferation and induces differentiation in
      mouse epidermis regardless of developmental stage. Thus, PPAR-alpha is an
      important regulator of epidermal homeostasis.

PMID- 16418734
TI  - Apoptosis in the hair follicle.
AB  - Apoptosis plays an important role in many physiological processes, ranging from
      morphogenetic events to adult tissue homeostasis, and defects in its regulation
      contribute to many disorders. Here we review molecular mechanisms of apoptosis in
      the hair follicle (HF), whose cyclical growth pattern is repeatedly interrupted
      by apoptosis-driven involution (catagen). We review the common mechanisms
      underlying apoptosis in the HF during catagen, as well as differences in the
      regulation of apoptosis between distinct HF cell populations. An overview is
      provided on the expression and function of molecules involved in the control of
      various phases of the apoptotic process during catagen.

PMID- 16418735
TI  - Identification of remodeling and spacing factor 1 (rsf-1, HBXAP) at chromosome
      11q13 as a putative oncogene in ovarian cancer.

PMID- 16418736
TI  - Compound heterozygosity for two MSH6 mutations in a patient with early onset of
      HNPCC-associated cancers, but without hematological malignancy and brain tumor.
AB  - Heterozygous germline mutations in the human mismatch repair (MMR) genes MLH1,
      PMS2, MSH2 and MSH6 predispose to the hereditary non-polyposis colorectal cancer
      (HNPCC) syndrome. Biallelic mutations in these genes have been reported for a
      limited number of cases resulting in hematological malignancies, brain tumors and
      gastrointestinal tumors early in childhood. These tumor phenotypes are frequently
      associated with cafe-au-lait spots (CALS), one of the clinical hallmarks of
      neurofibromatosis type 1 (NF1). We report the first case of compound
      heterozygosity for two MSH6 mutations resulting in a nonconservative amino-acid
      change of a conserved residue and in a premature stop codon in a patient who
      developed rectal and endometrial cancer at ages 19 and 24 years, respectively,
      and presented few CALS in a single body segment. Immunohistochemistry and Western
      blotting revealed only residual expression of the MSH6 protein in the normal
      cells. The disease history resembles the HNPCC phenotype rather than a phenotype
      associated with biallelic MMR gene mutations. Therefore, we assume that one or
      both mutations abolish protein function only partially, further supported by the
      parents, which are both carriers of one of the mutations each, and not affected
      by the disease at ages 57 and 58 years. Our data suggest considering biallelic
      mutations in MMR genes for patients who develop HNPCC-associated tumors at an
      unusually young age of onset, even without hematological or brain malignancies.

PMID- 16418733
TI  - Keratinocyte apoptosis in epidermal development and disease.
AB  - Keratinocyte (KC) apoptosis plays a critical role in regulating epidermal
      development and restraining carcinogenesis. Apoptosis balances proliferation to
      maintain epidermal thickness, contributes to stratum corneum formation and may
      eliminate pre-malignant cells. Apart from the normal developmental program, KC
      apoptosis can be triggered by UV light and other stimuli. Dysfunctional apoptosis
      occurs in some skin diseases, such as psoriasis and skin cancer. Here we review
      the current state of knowledge of KC apoptosis, with particular focus on
      apoptotic signaling pathways and molecular mechanisms of apoptosis control, and
      discuss new insights into the complex role of apoptosis in skin carcinogenesis
      that are emerging from mouse models.

PMID- 16418737
TI  - Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility.
AB  - Alleles of tumor necrosis factor-alpha (TNF-alpha) gene have been inconsistently
      associated with systemic lupus erythematosus (SLE), particularly the 308-A/G
      functional promoter polymorphism. To generate large-scale evidence on whether 308
      A/G promoter polymorphism is associated with SLE susceptibility we have conducted
      a meta-analysis. We have identified 21 studies of this polymorphism and SLE using
      MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect),
      A/A+A/G (dominant effect), and A allele in fixed or random effects models. All
      control samples were in Hardy-Weinberg proportion. The overall odds ratio (OR) of
      the A/A genotype was 3.2 (95% CI=2.0-5.3, P<0.001). Stratification by ethnicity
      indicated that the A/A genotype was associated with SLE in European-derived
      population (OR=4.0, CI=2.5-6.4, P<0.001). No association was detected in Asian
      derived population (OR, 1.3, CI=0.3-6.3, P=0.76). The overall OR for the risk
      genotypes (A/A and A/G) was 2.0 (CI=1.3-3.1, P<0.001). Similar results were found
      between the risk allele A and SLE where a significant association was found in
      European population (OR=2.1, CI=1.6-2.7, P<0.001), but not in Asian (OR=1.4,
      CI=0.8-2.3, P=0.2) or African (OR=1.2, CI=0.6-2.5, P=0.59) populations. In
      summary, this meta-analysis demonstrates that the TNF-alpha promoter -308 A/G
      polymorphism may confer susceptibility to SLE, especially in European-derived
      population.

PMID- 16418739
TI  - Mutation screening in patients with syndromic craniosynostoses indicates that a
      limited number of recurrent FGFR2 mutations accounts for severe forms of Pfeiffer
      syndrome.
AB  - Crouzon Syndrome (CS), Pfeiffer syndrome (PS) and the phenotypically related
      Jackson-Weiss (JW) variant are three craniosynostotic conditions caused by
      heterozygous mutations in Fibroblast Growth Factor Receptor (FGFR) genes.
      Screening a large cohort of 84 patients with clinical features of CS, PS or JW by
      direct sequencing of genomic DNA, enabled FGFR1, 2 or 3 mutation detection in 79
      cases. Mutations preferentially occurred in exons 8 and 10 of FGFR2 encoding the
      third Ig loop of the receptor. Among the 74 FGFR2 mutations that we identified,
      four were novel including three missense substitutions causing CS and a 2 bp
      deletion creating a premature stop codon and producing JW phenotype. Five FGFR2
      mutations were found in one of the two tyrosine kinase subdomains and one in the
      Ig I loop. Interestingly, two FGFR2 mutations creating cysteine residues (W290C
      and Y340C) caused severe forms of PS while conversion of the same residues into
      another amino-acid (W290G/R, Y340H) resulted in Crouzon phenotype exclusively.
      Our data provide conclusive evidence that the mutational spectrum of FGFR2
      mutations in CS and PS is wider than originally thought. Genotype-phenotype
      analyses based on our cohort and previous studies further indicate that in spite
      of some overlap, PS and CS are preferentially accounted for by two distinct sets
      of FGFR2 mutations. A limited number of recurrent amino-acid changes (W290C,
      Y340C, C342R and S351C) is commonly associated with the most severe Pfeiffer
      phenotypes of poor prognosis.

PMID- 16418740
TI  - The adiponectin gene is associated with adiponectin levels but not with
      characteristics of the insulin resistance syndrome in healthy Caucasians.
AB  - Low concentrations of adiponectin, the protein product of the APM1 gene, have
      been reported to be associated with obesity and insulin resistance. However,
      contrasting results have been described on the genetic variability in APM1 and
      characteristics of the metabolic syndrome and adiponectin serum concentrations.
      In the present study, we investigated the association of the two most well-known
      SNPs of APM1 (+45T>G and +276G>T) and their haplotypes, with serum adiponectin
      concentrations, metabolic parameters and intima-media thickness of the carotid
      arteries in 1,745 well-phenotyped asymptomatic unrelated Caucasian subjects of
      the SAPHIR cohort. The common T-allele (88.5%) of SNP +45T>G and the common G
      allele (70.5%) of SNP +276G>T were associated with significantly lower serum
      adiponectin levels (P = 0.0008 and P = 0.00005, respectively). The most frequent
      haplotype TG (59.0%) defined by both loci showed a strong association with lower
      serum adiponectin concentrations (P = 0.000000002). A clear effect per copy of
      the respective haplotype was observed. This association was most pronounced in
      lean and insulin-sensitive subjects. The two less common haplotypes TT (29.5%)
      and GG (11.5%) were associated with higher serum adiponectin levels in a dose
      dependent association. Interestingly, no significant association between the
      adiponectin 45-276 haplotypes and the majority of parameters of the metabolic
      syndrome or intima-media thickness of the carotid arteries was found in our
      study. In summary, we replicated a strong association of the adiponectin 45-276
      genotypes and haplotypes with adiponectin levels in healthy Caucasians. However,
      we could not confirm an association of this gene locus with metabolic parameters
      of the insulin resistance syndrome.

PMID- 16418738
TI  - Confirmation of mosaicism and uniparental disomy in amniocytes, after detection
      of mosaic chromosome abnormalities in chorionic villi.
AB  - Chromosome mosaicism is detected in about 1-2% of chorionic villi samples (CVS),
      and may be due to a postzygotic nondisjunction event generating a trisomic cell
      line in an initially normal conceptus (mitotic origin) or the postzygotic loss of
      one chromosome in an initially trisomic conceptus (meiotic origin and trisomy
      rescue). Depending on the distribution of the abnormal cell line, the mosaic can
      be confined to the placenta (CPM) or generalised to the fetus (TFM, true fetal
      mosaicism). Trisomy rescue could theoretically be associated with a 33.3%
      probability of uniparental disomy (UPD) in the fetus. The aim of this study was
      to determine the risk of fetal involvement in a cohort of numerical and
      structural chromosome mosaics revealed in chorionic villi by means of combined
      direct and long-term culture analyses; we also determined the incidence of UPD
      associated with mosaic aneuploidies and supernumerary markers involving imprinted
      chromosomes. A total of 273 of a consecutive series of 15,109 CVS evaluated
      during a period of 5 years showed a mosaic condition in direct preparations
      and/or long-term cultures; confirmatory amniocentesis was performed in 203 cases.
      The abnormal cell line was extended to the fetus in 12.8% cases in terms of
      structural and numerical abnormalities involving autosomes and sex chromosomes;
      the risk of TFM varied and depended on the placental tissue distribution of the
      abnormal cell line. One of the 51 cases in which the mosaic involved an imprinted
      chromosome showed UPD, thus indicating a risk of 1.96%.

PMID- 16418741
TI  - Socio-demographic influences on food purchasing among Canadian households.
AB  - OBJECTIVE: To characterize the relationships between selected socio-demographic
      factors and food selection among Canadian households. DESIGN: A secondary
      analysis of data from the 1996 Family Food Expenditure survey was conducted
      (n=10,924). Household food purchases were classified into one of the five food
      groups from Canada's Food Guide to Healthy Eating. Parametric and non-parametric
      modelling techniques were employed to analyse the effects of household size,
      composition, income and education on the proportion of income spent on each food
      group and the quantity purchased from each food group. RESULTS: Household size,
      composition, income and education together explained 21-29% of the variation in
      food purchasing. Households with older adults spent a greater share of their
      income on vegetables and fruit (P<0.0001), whereas households with children
      purchased greater quantities of milk products (P<0.0001). Higher income was
      associated with purchasing more of all food groups (P<0.0001), but the
      associations were nonlinear, with the strongest effects at lower income levels.
      Households where the reference person had a university degree purchased
      significantly more vegetables and fruit, and less meat and alternatives and
      'other' foods (P<0.0001), relative to households with the lowest education level.
      CONCLUSIONS: Household socio-demographic characteristics have a strong influence
      on food purchasing, with the purchase of vegetables and fruit being particularly
      sensitive. Results reinforce concerns about constraints on food purchasing among
      lower income households. Furthermore, the differential effects of income and
      education on food choice need to be considered in the design of public health
      interventions aimed at altering dietary behaviour.

PMID- 16418742
TI  - Comparison of three different dietary scores in relation to 10-year mortality in
      elderly European subjects: the HALE project.
AB  - OBJECTIVE: To investigate and compare the associations between dietary patterns
      and mortality using different European indexes of overall dietary quality.
      DESIGN, SETTING AND PARTICIPANTS: The HALE (Healthy Ageing: a Longitudinal study
      in Europe) population includes 2,068 men and 1,049 women, aged between 70 and 90
      years of 10 European countries. Subjects were followed for 10 years. This cohort
      study was conducted between 1988 and 2000. RESULTS: During the follow-up period,
      1,382 people died. The Mediterranean Diet Score (MDS) (HR: 0.82 with 95% CI: 0.75
      0.91), the Mediterranean Adequacy Index (MDI) (HR: 0.83 with 95% CI: 0.75-0.92)
      and the Healthy Diet Indicator (HDI)(HR: 0.89 with 95% CI: 0.81-0.98) were
      inversely associated with all-causes mortality. Adjustments were made for age,
      gender, alcohol consumption, physical activity, smoking, number of years of
      education, body mass index, chronic diseases at baseline and study centre.
      CONCLUSIONS: The MDS, the MDI and the HDI were significantly inversely related
      with mortality. SPONSORSHIP: This study is based on data of the HALE project and
      supported by a grant from the European Union (QLK6-CT-2000-00211) to D Kromhout.

PMID- 16418743
TI  - Dietary and genetic determinants of homocysteine levels among Mexican women of
      reproductive age.
AB  - OBJECTIVE: To evaluate the independent and joint effects of dietary folate,
      vitamin B(12) consumption and methylenetetrahydrofolate reductase (MTHFR)
      polymorphisms (677C>T and 1298A>C) on the circulating folate and homocysteine
      (Hcy) levels among Mexican women of reproductive age. DESIGN: A cross-sectional,
      population-based study. SUBJECTS: The first 130 healthy non-pregnant women (aged
      16-34 years) who agreed to participate in a reproductive cohort in Morelos,
      Mexico. MAIN OUTCOME MEASUREMENTS: Dietary intakes of vitamin B(12) and folate
      were estimated using a semiquantitative food frequency questionnaire. MTHFR
      677C>T and 1298A>C polymorphisms were ascertained using the PCR-based method.
      Serum levels of Hcy and folate were determined using high-performance liquid
      chromatography and radioimmunoassay, respectively. RESULTS: Genotype frequencies
      for the MTHFR 677C>T polymorphism were 21.5% (CC), 52.3% (CT) and 26.2% (TT)
      among Mexican women. Of the population, 22% had the MTHFR 1298AC genotype, while
      no individual carried the 1298CC genotype. We observed an increased level of Hcy
      among carriers of the 677TT genotype, compared to carriers of the 677CC genotype.
      The highest level of Hcy was observed among MTHFR 677TT carriers with low B(12)
      intake (<2.0 microg/day), which resulted with a significant interaction (P=0.01).
      CONCLUSION: Vitamin B(12) is an important determinant of Hcy levels in Mexico.
      Supplementation of folic acid with vitamin B(12) may be preferable when the MTHFR
      677T variant allele is prevalent.

PMID- 16418744
TI  - Structural variation in the human genome.
AB  - The first wave of information from the analysis of the human genome revealed SNPs
      to be the main source of genetic and phenotypic human variation. However, the
      advent of genome-scanning technologies has now uncovered an unexpectedly large
      extent of what we term 'structural variation' in the human genome. This comprises
      microscopic and, more commonly, submicroscopic variants, which include deletions,
      duplications and large-scale copy-number variants - collectively termed copy
      number variants or copy-number polymorphisms - as well as insertions, inversions
      and translocations. Rapidly accumulating evidence indicates that structural
      variants can comprise millions of nucleotides of heterogeneity within every
      genome, and are likely to make an important contribution to human diversity and
      disease susceptibility.

PMID- 16418745
TI  - Hearing silence: non-neutral evolution at synonymous sites in mammals.
AB  - Although the assumption of the neutral theory of molecular evolution - that some
      classes of mutation have too small an effect on fitness to be affected by natural
      selection - seems intuitively reasonable, over the past few decades the theory
      has been in retreat. At least in species with large populations, even synonymous
      mutations in exons are not neutral. By contrast, in mammals, neutrality of these
      mutations is still commonly assumed. However, new evidence indicates that even
      some synonymous mutations are subject to constraint, often because they affect
      splicing and/or mRNA stability. This has implications for understanding disease,
      optimizing transgene design, detecting positive selection and estimating the
      mutation rate.

PMID- 16418746
TI  - Digital genetics: unravelling the genetic basis of evolution.
AB  - Digital genetics, or the genetics of digital organisms, is a new field of
      research that has become possible as a result of the remarkable power of
      evolution experiments that use computers. Self-replicating strands of computer
      code that inhabit specially prepared computers can mutate, evolve and adapt to
      their environment. Digital organisms make it easy to conduct repeatable,
      controlled experiments, which have a perfect genetic 'fossil record'. This allows
      researchers to address fundamental questions about the genetic basis of the
      evolution of complexity, genome organization, robustness and evolvability, and to
      test the consequences of mutations, including their interaction and
      recombination, on the fate of populations and lineages.

PMID- 16418747
TI  - Literature mining for the biologist: from information retrieval to biological
      discovery.
AB  - For the average biologist, hands-on literature mining currently means a keyword
      search in PubMed. However, methods for extracting biomedical facts from the
      scientific literature have improved considerably, and the associated tools will
      probably soon be used in many laboratories to automatically annotate and analyse
      the growing number of system-wide experimental data sets. Owing to the increasing
      body of text and the open-access policies of many journals, literature mining is
      also becoming useful for both hypothesis generation and biological discovery.
      However, the latter will require the integration of literature and high
      throughput data, which should encourage close collaborations between biologists
      and computational linguists.

PMID- 16418748
TI  - Towards multidimensional genome annotation.
AB  - Our information about the gene content of organisms continues to grow as more
      genomes are sequenced and gene products are characterized. Sequence-based
      annotation efforts have led to a list of cellular components, which can be
      thought of as a one-dimensional annotation. With growing information about
      component interactions, facilitated by the advancement of various high-throughput
      technologies, systemic, or two-dimensional, annotations can be generated.
      Knowledge about the physical arrangement of chromosomes will lead to a three
      dimensional spatial annotation of the genome and a fourth dimension of annotation
      will arise from the study of changes in genome sequences that occur during
      adaptive evolution. Here we discuss all four levels of genome annotation, with
      specific emphasis on two-dimensional annotation methods.

PMID- 16418749
TI  - Decoding the research exemption.
AB  - While debate continues as to whether genetic sequences, which many argue
      represent natural phenomena rather than inventions, should be subject to standard
      patent protections, issuance of patents that claim DNA sequences remains common
      practice. In an attempt to insulate researchers from patent claims that could
      hinder scientific progress, many countries have provided general exemptions for
      scientific research. However, there is no international consensus about the
      extent of required protections, and even existing exemptions vary widely in
      clarity and are limited in practical application. We believe that gene patents
      raise several unique issues that are inadequately handled by the current research
      exemptions.

PMID- 16418750
TI  - Work stress, weight gain and weight loss: evidence for bidirectional effects of
      job strain on body mass index in the Whitehall II study.
AB  - OBJECTIVE: Previous research has focused on overall associations between work
      stress and body mass index (BMI) ignoring the possibility that stress may cause
      some people to eat less and lose weight and others to eat more. Using
      longitudinal data, we studied whether work stress induced weight loss in lean
      individuals and weight gain in overweight individuals. DESIGN: Prospective cohort
      study. SUBJECTS: A total of 7965 British civil servants (5547 men and 2418 women)
      aged 35-55 at study entry (The Whitehall II study). MEASUREMENTS: Work stress,
      indicated by the job strain model and measured as job control, job demands and
      job strain, was assessed at baseline and BMI at baseline and at 5-year follow-up.
      RESULTS: In men, the effect of job strain on weight gain and weight loss was
      dependent on baseline BMI (P</=0.03). In the leanest quintile (BMI<22 kg/m(2)) at
      baseline, high job strain and low job control were associated with weight loss by
      follow-up, whereas among those in the highest BMI quintile (>27 kg/m(2)), these
      stress indicators were associated with subsequent weight gain. No corresponding
      interaction was seen among women. CONCLUSION: Inconsistent findings reported by
      previous studies of stress and BMI have generally been interpreted to indicate
      the absence of an association. In light of our results, the possibility of
      differential effects of work stress should also be taken into account.

PMID- 16418751
TI  - Body fat and circulating leukocytes in children.
AB  - OBJECTIVE: To determine the effects of obesity on baseline levels of circulating
      granulocytes, monocytes, and lymphocyte subtypes in otherwise healthy children.
      DESIGN: Two group comparison of leukocytes in normal weight control and
      overweight children. SUBJECTS: In total, 38 boys and girls, ages 6-18 years,
      divided in two groups: normal weight, (NW, BMI<85th %tile, n=15) and overweight
      (OW, body mass index (BMI)>85th %tile, n=23). MEASUREMENTS: BMI obtained from
      direct measures of height and body mass. Body fat was assessed by DEXA. Complete
      blood counts (CBC) were obtained by standard clinical hematology methods and
      surface antigen staining by flow cytometry. RESULTS: The OW group compared to the
      NW group had increased total leukocytes counts (P=0.011), neutrophils (P=0.006),
      monocytes (P=0.008), total T (CD3) lymphocytes (P=0.022), and Helper T (CD4(+))
      cells (P=0.003). Significant correlations were evident between leukocytes, and
      BMI percentile, BMI, or percent body fat. Neither lean body mass nor VO(2peak)
      per unit lean body mass were significantly related to any of the leukocytes.
      Percent body fat and BMI percentile were positively correlated (P<0.05) to total
      T cells (CD3) and/or helper T cells (CD4(+)). CONCLUSION: A group of 23
      overweight children displayed elevated counts in most types of circulating immune
      cells, suggesting the presence of low-grade systemic inflammation, a known
      pathogenetic mechanism underlying most long-term complications of obesity. Our
      data provide an additional rationale for the importance of avoiding or correcting
      pediatric obesity.

PMID- 16418752
TI  - Combined effects of oral oleoyl-estrone and limited food intake on body
      composition of young overweight male rats.
AB  - OBJECTIVE: The combined effects of limited food intake and OE treatment have been
      analysed in order to determine whether hypocaloric diets enhance the slimming
      effects of OE on mature overweight male rats. Two levels of dietary limitation at
      50 and 25% of a standard intake were established, roughly corresponding to the
      human LCDs and VLCDs. DESIGN: Wistar male rats (6 weeks old) were made overweight
      by a cafeteria diet. After transition to standard diet, they were subjected to
      food restriction: down to 50 or 25% with respect to the transition period. Half
      the animals were given daily oral gavages of 10 nmol/g oleoyl-estrone (OE), and
      the rest received only the vehicle during 10 days. MEASUREMENTS: Changes in
      weight and body composition: water, lipid, protein or gross energy were
      determined by comparing the final pool size with that of day 0, calculated from
      the initial body weight and the composition of untreated rats. Energy and
      nitrogen balances were estimated. Plasma levels of metabolites and hormones were
      also measured. RESULTS: OE induced changes in body composition similar to those
      elicited by a 50% reduction in food, with massive loss of lipid and energy. OE
      treated rats ate less than the controls, but additional effects on body
      composition on reduced diet were minimal. OE improved metabolic homoeostasis:
      better maintained glycaemia, lower cholesterol and shallower hormonal changes,
      but at the expense of slightly increased protein mobilisation. CONCLUSIONS: The
      data presented suggest that no advantages are accomplished by combining OE
      treatment and hypocaloric diets compared with OE alone, at least under the
      experimental conditions tested, since the effects were not additive. Despite OE
      affecting food intake, mechanisms other than that are deemed responsible for the
      mobilisation of body fat, since intake alone cannot explain the effects on body
      weight, nor the metabolic and hormonal changes in OE-treated rats. It is
      concluded that the combination of food restriction and OE may result in unwanted
      increased protein mobilisation with no synergy between both slimming treatments.

PMID- 16418753
TI  - Atomoxetine for weight reduction in obese women: a preliminary randomised
      controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Atomoxetine is a potent central norepinephrine uptake
      inhibitor, currently marketed for treatment of attention-deficit/hyperactivity
      disorder (ADHD). With the understanding that noradrenergic agents could be useful
      in assisting obese individuals to lose weight, we conducted this preliminary
      study to evaluate short-term efficacy and safety of atomoxetine in obese adults.
      DESIGN: At 12-week randomised, double-blind, placebo-controlled trial, conducted
      at Duke University Medical Centre, USA, from May 2004 to December 2004.
      PARTICIPANTS: A total of 30 obese women (mean (s.e.) body mass index of 36.1
      (0.6) kg/m2). INTERVENTIONS: Participants were randomly assigned to receive
      atomoxetine (n=15) or placebo (n=15). All participants were advised to follow a
      balanced hypocaloric diet (500 kcal/day deficit). Atomoxetine therapy was started
      at 25 mg/day orally, with gradual increase to 100 mg/day over 1 week. Placebo
      dosing was identical. MEASUREMENTS: Body weight in kilograms was the primary
      outcome measure. Other measurements included waist circumference, blood pressure
      and heart rate, fasting plasma glucose and lipids, and depressive symptoms.
      RESULTS: Last-observation-carried-forward analysis of the available data for
      participants who had completed at least one post-randomisation assessment,
      demonstrated that the atomoxetine group (n=12) lost more body weight over the 12
      week period than the placebo (n=14) group (mean (s.e.) -3.6 (1.0) kg (-3.7% loss)
      vs 0.1 (0.4) kg (0.2% gain); F (4,96)=11.9; P<0.0001). Three participants in the
      atomoxetine group and none in the placebo group lost >or=5% weight. Side effects
      were minimal. CONCLUSION: Atomoxetine demonstrated modest short-term weight loss
      efficacy relative to placebo in this preliminary study of obese women.

PMID- 16418754
TI  - Body mass index and waist circumference as determinants of coronary artery
      disease in Taiwanese adults with type 2 diabetes mellitus.
AB  - OBJECTIVE: This study examined the association between body mass index (BMI) and
      waist circumference (WC) and coronary artery disease (CAD) in Taiwanese type 2
      diabetic patients. METHODS: A total of 1183 (558 men and 625 women) patients aged
      62.4+/-11.6 years were studied. CAD was diagnosed by history or an
      electrocardiogram by Minnesota codes. RESULTS: The respective cutoffs of BMI and
      WC as determined by the receiver operating characteristic curves were 24.5 kg/m2
      and 90 cm for men, and 25 kg/m2 and 80 cm for women. Distributions of CAD
      prevalence and multivariate-adjusted odds ratio (MAOR) for BMI cutoffs of 24.5
      and 25 kg/m2 were quite similar in men. MAOR for WC above the respective cutoffs
      for men and women was 1.832 (1.267-2.648) and 1.450 (0.956-2.200, 0.05<P<0.1),
      and for BMI> or = 25 kg/m2 was 1.759 (1.213-2.551) and 1.471 (1.052-2.058) for
      men and women, respectively. Patients with BMI> or = 25 kg/m2 and WC > or = 90 cm
      for men or > or = 80 cm for women had the highest risk of CAD when compared to
      those without either risk factor, with respective MAOR of 2.053 (1.352-3.118) and
      1.698 (1.071-2.691). CONCLUSION: The recommended BMI and WC cutoffs for obesity
      for Asian adults are associated with CAD in Taiwanese T2DM.

PMID- 16418755
TI  - The office candy dish: proximity's influence on estimated and actual consumption.
AB  - OBJECTIVE AND PURPOSE: Although there is increasing interest in how environmental
      factors influence food intake, there are mixed results and misunderstandings of
      how proximity and visibility influence consumption volume and contribute to
      obesity. The objective of this paper is to examine two questions: first, how does
      the proximity and salience of a food influence consumption volume? Second, are
      proximate foods consumed more frequently because they are proximate, or are they
      consumed more frequently because people lose track of how much they eat? RESEARCH
      METHODS AND PROCEDURES: The 4-week study involved the chocolate candy consumption
      of 40 adult secretaries. The study utilized a 2 x 2 within-subject design where
      candy proximity was crossed with visibility. Proximity was manipulated by placing
      the chocolates on the desk of the participant or 2 m from the desk. Visibility
      was manipulated by placing the chocolates in covered bowls that were either clear
      or opaque. Chocolates were replenished each evening, and placement conditions
      were rotated every Monday. Daily consumption was noted and follow-up
      questionnaires were distributed and analyzed. RESULTS: There were main effects
      for both proximity and visibility. People ate an average of 2.2 more candies each
      day when they were visible, and 1.8 candies more when they were proximately
      placed on their desk vs 2 m away. It is important to note, however, that there
      was a significant tendency for participants to consistently underestimate their
      daily consumption of proximately placed candies (-0.9) and overestimate their
      daily consumption of less proximately placed candies (+0.5). DISCUSSION: These
      results show that the proximity and visibility of a food can consistently
      increase an adult's consumption of it. In addition, these results suggest that
      people may be biased to overestimate the consumption of foods that are less
      proximate, and to underestimate those that are more proximate. Knowing about
      these deviation tendencies is important for those attempting effectively monitor
      their consumption of fat and sugar.

PMID- 16418756
TI  - Fully automated large-scale assessment of visceral and subcutaneous abdominal
      adipose tissue by magnetic resonance imaging.
AB  - OBJECTIVE: To describe and evaluate a fully automated method for characterizing
      abdominal adipose tissue from magnetic resonance (MR) transverse body scans.
      METHODS: Four MR pulse sequences were applied: SE, FLAIR, STIR, and FRFSE. On 39
      subjects, each abdomen was traversed by 15 contiguous transaxial images. The
      total abdominal adipose tissue (TAAT) was calculated from thresholds obtained by
      slice histogram analysis. The same thresholds were also used in the manual volume
      calculation of TAAT, subcutaneous abdominal adipose tissue (SAAT) and visceral
      abdominal adipose tissue (VAAT). Image segmentation methods, including edge
      detection, mathematical morphology, and knowledge-based curve fitting, were used
      to automatically separate SAAT from VAAT in various 'nonstandard' cases such as
      those with heterogeneous magnetic fields and movement artefacts. RESULTS: The
      percentage root mean squared errors of the method for SAAT and VAAT ranged from
      1.0 to 2.7% for the four sequences. It took approximately 7 and 15 min to
      complete the 15-slice volume estimation of the three adipose tissue classes using
      automated and manual methods, respectively. CONCLUSION: The results demonstrate
      that the proposed method is robust and accurate. Although the separation of SAAT
      and VAAT is not always perfect, this method could be especially helpful in
      dealing with large amounts of data such as in epidemiological studies.

PMID- 16418757
TI  - Lifecourse predictors of normal metabolic parameters in overweight and obese
      adults.
AB  - OBJECTIVE: Not all overweight and obese individuals appear to be at equal risk of
      developing metabolic abnormalities. We sought to examine the effect of factors
      from different stages of life on risk of metabolic abnormalities at age 50 years
      in overweight and obese adults. DESIGN AND SUBJECTS: Longitudinal study of all
      persons born in Newcastle upon Tyne, UK in May and June 1947 and followed to age
      50 years when a clinical examination took place and a detailed questionnaire on
      health and lifestyle was completed. Participants in this study (n=223) were those
      defined as being overweight or obese with a body mass index (BMI) greater than or
      equal to 25 at age 50 years. Subjects were defined as 'metabolically normal' if
      they had normal lipids, glucose and blood pressure. RESULTS: Lower BMI was the
      strongest predictor of remaining metabolically normal in both men and women.
      After adjusting for BMI, lower levels of cigarette smoking and higher levels of
      physical activity were independently associated with being metabolically normal
      in men. No other factors were independently associated with being metabolically
      normal in women. A stronger inverse relationship between BMI and metabolic status
      was found in men (Odds ratio (OR) per unit increase in BMI=0.65, 95% confidence
      intervals (95% CI) 0.52-0.81) than in women (OR=0.90, 95% CI 0.82-0.99). No
      association was seen for factors operating in fetal, infant and childhood life.
      CONCLUSIONS: Adult factors made a greater contribution to remaining metabolically
      normal than birth or childhood factors in this sample of overweight and obese
      adults. A lower adult BMI appeared to reduce the risk in men and women and lower
      cigarette smoking and higher level of physical activity also independently
      reduced the risk in men. Public health policy to reduce the burden of morbidity
      associated with obesity should continue to encourage weight loss, physical
      activity and smoking cessation.

PMID- 16418758
TI  - The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral
      adipose tissues in human obesity and type 2 diabetes.
AB  - BACKGROUND: Long-chain fatty acids (LCFAs) cross the plasma membrane via a
      protein-mediated mechanism involving one or more LCFA-binding proteins. Among
      these, FAT/CD36 has been identified as key LCFA transporter in the heart and
      skeletal muscle, where it is regulated acutely and chronically by insulin. In
      skeletal muscle, FAT/CD36 expression and/or subcellular distribution is altered
      in obesity and type 2 diabetes. There is limited information as to whether the
      expression of this protein is also altered in subcutaneous and/or visceral
      adipose tissue depots in human obesity or type 2 diabetes. OBJECTIVES: To compare
      (a) the expression of FAT/CD36 in subcutaneous and visceral adipose tissue depots
      in lean, overweight, and obese individuals and in type 2 diabetics, (b) to
      determine whether the protein expression of FAT/CD36 in these depots is
      associated with the severity of insulin resistance (type 2
      diabetes>obese>overweight/lean) and (c) whether FAT/CD36 protein expression in
      these adipose tissue depots is associated with alterations in circulating
      substrates and hormones. SUBJECTS: Subjects who were undergoing abdominal surgery
      and who were lean (n=10; three men, seven women), overweight (n=10; three men,
      seven women) or obese (n=7; one man, six women), or who had been diagnosed with
      type 2 diabetes (n=5; one man, four women) participated in this study.
      MEASUREMENTS: Subcutaneous and visceral adipose tissue samples, as well as blood
      samples, were obtained from the subjects while under general anesthesia. Adipose
      tissue samples were analyzed for FAT/CD36 using Western blotting. Serum samples
      were analyzed for glucose, insulin, FFA and leptin. BMI was also calculated.
      RESULTS: Subcutaneous adipose tissue FAT/CD36 expression was upregulated by +58,
      +76 and +150% in overweight, obese and type 2 diabetics, respectively. Relative
      to subcutaneous adipose tissue, visceral adipose tissue FAT/CD36 expression was
      upregulated in lean (+52%) and overweight subjects (+30%). In contrast, in obese
      subjects and type 2 diabetics, no difference in FAT/CD36 protein expression was
      observed between their subcutaneous and visceral adipose tissue depots (P>0.05).
      The subcutaneous adipose tissue FAT/CD36 expression (R=0.85) and the visceral
      adipose tissue FAT/CD36 expression (R=0.77) were associated with alteration in
      BMI and circulating glucose and insulin. CONCLUSIONS: Subcutaneous adipose tissue
      FAT/CD36 expression is upregulated in obesity and type 2 diabetes. As FAT/CD36
      expression is not different in lean, overweight and obese subjects, and was only
      increased in type 2 diabetics, it appears that visceral adipose tissue FAT/CD36
      may respond in a less dynamic manner to metabolic disturbances than subcutaneous
      adipose tissue FAT/CD36.

PMID- 16418759
TI  - N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic
      offspring.
AB  - OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n
      3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)
      induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats,
      fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of
      five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation.
      The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS:
      Lipid peroxidation was measured as the concentrations of plasma thiobarbituric
      acid reactive substances (TBARS), and the total antioxidant status was determined
      by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma
      vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in
      erythrocytes. The plasma lipid concentrations and fatty acid composition were
      also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol
      concentrations, whereas macrosomia was associated with enhanced plasma
      cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N
      3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC
      values in diabetic rats and their macrosomic offspring. EPAX diet increased the
      diminished vitamin A levels in diabetic mothers and vitamin C concentrations in
      macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide
      dismutase and glutathione peroxidase activities in diabetic and macrosomic
      animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid
      metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA
      diet improved hyperlipidemia and restored antioxidant status in diabetic dams and
      MAC offspring.

PMID- 16418760
TI  - Metabolic and physiological effects of ingesting extracts of bitter orange, green
      tea and guarana at rest and during treadmill walking in overweight males.
AB  - OBJECTIVE: This study examined the acute effects of ingesting a widely used
      commercial formula containing extracts of bitter orange, green tea and guarana
      (Gx) on the metabolic rate and substrate utilisation in overweight, adult males
      at rest (study 1) and during treadmill walking (study 2). SUBJECTS: Two different
      groups of 10 sedentary males with more than 20% body fat participated in studies
      1 and 2. DESIGN: In each study, subjects participated in two experimental trials
      during which they were given two 500 mg capsules containing either Gx or a
      placebo (P) in a counterbalanced double-blind manner. Doses of the main active
      ingredients were 6 mg of synephrine, 150 mg caffeine and 150 mg catechin
      polyphenols. MEASUREMENTS: In study 1, subjects completed 7 h supine rest with
      baseline measures taken during the first hour, with expired gases, blood
      pressure, heart rate and venous blood being collected every 30 min for the
      remaining 6 h following ingestion of Gx or P. In study 2, subjects exercised for
      60 min at 60% heart rate reserve following ingestion of Gx or P 1 h previously.
      Venous blood samples were collected twice at rest and at 5, 10, 15, 20, 30, 40,
      50 and 60 min, with expired gas measurements taken at 4, 9, 14, 19, 29, 39, 49
      and 59 min. In both studies, venous blood was analysed for NEFA, glycerol,
      glucose and lactate concentrations, while expired gases were used to calculate
      ATP production from carbohydrate and NEFA, as well as the total substrate
      utilised. RESULTS AND CONCLUSION: The results did not show any significant effect
      of Gx ingestion on total ATP utilisation during 6 h rest or during 60 min
      treadmill walking. Changes were observed in the relative contributions of CHO and
      NEFA oxidation to ATP production in both studies, such that there was an increase
      in ATP production from CHO and a decrease from NEFA. The increase in CHO
      oxidation was shown to be as high as 30% at rest.

PMID- 16418761
TI  - Is the current BMI obesity classification appropriate for black and white
      postmenopausal women?
AB  - OBJECTIVE: To evaluate the relation between body fatness (%Fat) and body mass
      index (BMI) and to evaluate the validity of the BMI standards for obesity
      established by the NIH in older black and white postmenopausal women. RESEARCH
      METHODS: Height, weight, BMI, and %Fat, assessed by DXA, were determined for 296
      healthy, independently living women ranging in age from 50 to 80 years (M+/-s.d.;
      64.4+/-7.8 years). RESULTS: Per NIH guidelines, 32% were classified as obese (>
      or = 30 kg/m2, mean BMI = 28.1+/-5.5 kg/m2). In contrast, using the %Fat
      criterion of 38% advocated by Lohman to define obesity, 47% of our sample was
      obese (mean %Fat=37.3+/-6.2%). A moderately high curvilinear relation existed
      between BMI and %Fat (R = 0.82, SEE = 3.57 %Fat, P<0.05). Race added meaningfully
      to the prediction of %Fat (P<0.05) such that for the same BMI, black women will
      have 1% lower body fatness than white women. Based on a %Fat > or = 38 as the
      criterion for obesity, receiver operating characteristic (ROC) analysis,
      performed separately by race, indicated that the currently accepted BMI cutpoint
      for obesity produced low sensitivity (69% and 61% for black and white women,
      respectively). Alternatively, BMI values > or = 28.4 kg/m2 for black women and >
      or = 26.9 kg/m2 for white women to define obesity maximized classification
      accuracy. CONCLUSION: We conclude that current BMI categories may not be
      appropriate for identifying obesity among postmenopausal women. Furthermore, the
      relation between BMI and %Fat is different in black compared to white women but
      remains constant from the sixth through the eighth decade of life.

PMID- 16418762
TI  - The Eating Inventory, body adiposity and prevalence of diseases in a quota sample
      of Czech adults.
AB  - OBJECTIVE: To study the relationships between the Eating Inventory (EI) factors
      (restraint, disinhibition and hunger), body adiposity and prevalence of selected
      diseases in a quota sample of Czech adults. SUBJECTS AND METHODS: The sample
      included 1429 men and 1624 women who were interviewed individually by trained
      investigators. The sample was quota representative--for gender, age, size of
      residential location, region and socioeconomic status in Czech adults.
      Anthropometric data, socioeconomic and lifestyle information were obtained.
      Subjects filled out the EI questionnaire. Physicians reported about subjects'
      morbidity. RESULTS: Backward stepwise regression analysis revealed that restraint
      and disinhibition were significant predictors of body mass index (BMI) along with
      gender, age, parental obesity, weight loss attempts, present dieting and
      educational level. The same factors plus income predicted the waist
      circumference. BMI and waist circumference were negatively related to restraint
      but positively to disinhibition. According to logistic regression analysis
      restraint and disinhibition were significantly associated with hypertension,
      cardiovascular diseases and hyperlipidaemia. Diabetes was significantly related
      to restraint and hunger scores. The observed association between EI factors and
      diseases remained significant even when BMI and age were taken into account.
      CONCLUSION: As shown in earlier studies, disinhibition was positively and
      restraint negatively associated with BMI and waist circumference. For the first
      time, factors of the EI were also identified as significant predictors of
      diseases characterizing the metabolic syndrome.

PMID- 16418763
TI  - Mesenteric fat thickness as an independent determinant of fatty liver.
AB  - OBJECTIVE: Mesenteric fat is drained by the portal circulation and has been
      suggested to be a key component in obesity-related health risk, notably the
      metabolic syndrome. There are increasing epidemiological and experimental data
      showing that fatty liver is another component of this multifaceted syndrome.
      Given their intimate anatomical and physiological relationships, we hypothesized
      that mesenteric fat thickness may be independently associated with the risk of
      fatty liver. To test this hypothesis, we examined the predictive role of various
      fat deposits including mesenteric fat thickness, and various metabolic variables
      on the risk of fatty liver. SUBJECTS AND METHODS: A total of 291 Chinese subjects
      (134 men and 157 women with a mean BMI of 23.7 kg/m2, range: 16.5-33.4 kg/m2)
      underwent ultrasound examination for measurement of mesenteric, subcutaneous and
      preperitoneal fat thickness, and for diagnosis of fatty liver. Body mass index,
      waist circumference, and waist-hip ratio were recorded. Blood pressure was
      measured. Fasting plasma glucose, insulin resistance, high-density lipoprotein
      cholesterol (HDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C),
      liver enzymes were determined by common methods. RESULTS: The subjects with fatty
      liver had greater abdominal fat thickness and higher anthropometric indexes than
      those without fatty liver. The subjects with fatty liver also showed higher blood
      pressure, worse lipid and glycaemic profile compared with those without fatty
      liver. Using multiple logistic regression analysis, mesenteric fat thickness was
      a risk factor of fatty liver, independent of body mass index, age, sex, insulin
      resistance, fasting plasma glucose, lipid and blood pressure. The odds ratio was
      1.5 (95% confidence interval: 1.27-1.77) for every 1 mm increase in the
      mesenteric fat thickness. Measurement of preperitoneal and subcutaneous fat
      deposits did not show significant associations with fatty liver. CONCLUSION:
      Mesenteric fat thickness measured on ultrasound is an independent determinant of
      fatty liver.

PMID- 16418764
TI  - Prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old,
      Danish men. Relation to sociodemography, physical dysfunction and low
      socioeconomic status: the Odense Androgen Study.
AB  - OBJECTIVE: To assess the prevalence of overweight, obesity and physical
      inactivity in 20- to 29-year-old men and to analyze whether sociodemography,
      physical dysfunction and low socioeconomic status are independent correlates of
      obesity and physical inactivity. DESIGN: Population-based, cross-sectional study.
      SUBJECTS: Seven hundred and eighty-three Caucasian, Danish men, aged 20-29 years
      recruited from 2042 respondents in a questionnaire survey of 3000 men, randomly
      drawn from the Danish Civil Registration System. METHODS: Questionnaire,
      interview and physical examination. RESULTS: The 783 included men and the 2042
      questionnaire respondents matched the background population demographically. The
      783 men matched the questionnaire respondents as regards BMI, physical activity,
      chronic disease, medication, smoking, sociodemography and socioeconomic status.
      The prevalence of overweight and obesity was 31.7 and 7.9%, respectively (World
      Health Organization criteria). Using waist circumference (WC) cutoffs of 94 and
      102 cm, the prevalence was 16.2 and 10.6%, respectively; 24.4% were physically
      inactive. BMI and WC increased significantly from age 20 to 29 years. Physical
      activity decreased significantly with age and correlated inversely with WC, but
      not with BMI. Occupation, geography, partner status, fatherhood and tobacco
      exposure were independently related with obesity and physical inactivity. Obesity
      was also related to musculoskeletal complaints, whereas chronic diseases and low
      educational level were associated with physical inactivity. Age was not
      independently related with either outcome. CONCLUSION: In affluent societies,
      sociodemographic changes may partly explain the age-related decrease in physical
      activity and the parallel increase in WC and BMI.

PMID- 16418765
TI  - Change in height, weight and body mass index: Longitudinal data from the HUNT
      Study in Norway.
AB  - OBJECTIVE: The aim of this study was to analyse changes in body weight and
      height, and the changes in the prevalence of overweight and obesity. DESIGN:
      Prospective population based study with 11-year follow-up. SUBJECTS: Norwegian
      men (n=21565) and women (n=24337) aged 20 years or more who participated in two
      health surveys, the first in 1984-1986 and the other in 1995-1997. MEASUREMENTS:
      Height and weight were measured by using standardised procedures at both surveys,
      and we computed body mass index (BMI) as weight in kilo divided by the squared
      value of height in meters. RESULTS: Participants who were younger than 50 years
      at the first survey showed a large increase in body weight, and men and women
      aged 20-29 years increased their weight with an average of 7.9 kg and 7.3 kg,
      respectively. Contradictory, participants who were 70 years or older had on
      average a weight loss. The prevalence of overweight (BMI=25.0-29.9 kg/m(2)) and
      obesity (BMI>/=30 kg/m(2)) increased between the surveys, especially in the
      youngest age groups. Overall, the proportion classified as obese increased from
      6.7 to 15.5% among men and from 11.0 to 21.0% among women. Some of this increase
      was due to a reduction in height, which was most pronounced in the oldest age
      groups. CONCLUSION: During approximately 10 years, body weight increased in all
      age groups below 70 years, and the prevalence of overweight and obese persons was
      approximately 20% higher at the second survey compared with the first survey.

PMID- 16418766
TI  - Virological aspects of Epstein-Barr virus infections.
AB  - Epstein-Barr virus (EBV) is usually maintained in an asymptomatic and latent form
      by the host immune system, and primarily by EBV-specific cytotoxic T cells
      (CTLs). However, EBV has been linked to several refractory diseases such as EBV
      associated hemophagocytic syndrome(EBV-AHS) and chronic active EBV infection
      (CAEBV). In these ectopic diseases, EBV infects T/NK cells, causing severe
      immunodeficiency with a very high EBV load. In recent years, the laboratory
      procedure to assess these types of EBV infections has been improved. In
      particular, real-time polymerase chain reaction (PCR) has been used to quantify
      the EBV load, and the MHC: peptide tetramer assay has been used to quantitate EBV
      specific CTLs; these tests have been employed for the management of the illnesses
      associated with EBV infection. Here, we have reviewed the recent progress in the
      clinical application of these assays. The pathogenesis of EBV-infected T/NK
      cells, and the host immune response to infection, including the roles carried out
      by innate immunity and inflammatory cytokines, are likely to be revealed in the
      future.

PMID- 16418767
TI  - Mycobacterium tuberculosis complex in atherosclerosis.
AB  - In recent years, the results of some studies have revealed the possible potential
      role of several infectious agents in the inflammatory mechanism of
      atherosclerosis. The detection of specific antibodies against microorganisms such
      as and as well as Chlamydia pneumoniae and cytomegalovirus as well as antibodies
      directed to heat shock proteins in the sera of atherosclerotic patients and the
      presence of genomic material in atheromatous plaques all provide evidence
      supporting the presumptive role of infectious agents in atherosclerosis. There
      are some findings that can be accepted as clues for the possible involvement of
      Mycobacterium tuberculosis in atherosclerosis. These consist of the presence of
      high levels of mycobacterial heat shock protein 65 in atherosclerotic patients,
      and in animal studies, the detection of atherosclerotic changes in the vascular
      wall of animals vaccinated with recombinant heat shock protein 65, and
      Mycobacterium tuberculosis containing heat shock protein 65. The probable
      proatherogenic effect of the specific immune response to BCG-associated heat
      shock protein was also suggested. The mycobacterium cell wall contains a
      phospholipid, phosphatidylinositol, which was shown to have a procoagulant effect
      similar to that of a cytomegalovirus possessing phosphatidylserine, another
      phospholipid showing a procoagulant effect. These data suggest that Mycobacterium
      tuberculosis may also be involved in the pathogenesis of atherosclerosis.

PMID- 16418768
TI  - The augmentation of TNFalpha-induced cell death in murine L929 fibrosarcoma by
      the pan-caspase inhibitor Z-VAD-fmk through pre-mitochondrial and MAPK-dependent
      pathways.
AB  - We investigated the mechanism of the pan-caspase inhibitor z-VAD-fmk's
      augmentation of TNFalpha-induced L929 cell death and found this mechanism differs
      from that of TNFalpha-induced L929 cell death. In the presence of 20 ng/ml
      TNFalpha, z-VAD-fmk initiated apoptosis and necrosis in the majority of L929
      cells as measured by an agarose gel electrophoresis and lactate
      dehydrogenase(LDH)activity based assay. Mitochondrial permeability transition
      (MPT) inhibitor (cyclosporine A) effectively inhibited z-VAD-fmk-augmented cell
      death. In addition, z-VAD-fmk plus TNFalpha increased Bax expression without
      affecting Bcl-2 and cytochrome expression. Western-blot analysis showed that z
      VAD-fmk plus TNFalpha caused persistent JNK activation and ERK inactivation.
      Poly(ADP-ribose) polymerase (PARP) inhibitor (DPQ) effectively reversed the cell
      death which was augmented by z-VAD-fmk, and z-VAD-fmk plus TNFalpha also caused
      PARP cleavage to an 85 KDa fragment. These results indicate that in the presence
      of TNFalpha, z-VAD-fmk further augments cell death which requires the
      mitochondrial permeability transition and the JNK activation. However, we did not
      detect the changes in cytochrome c expression and the participation of caspase-9
      in this process, suggesting that there might exist an unknown signal pathway(s)
      from the mitochondria to the downstream protein PARP, which is cleaved in a
      caspase-independent manner.

PMID- 16418769
TI  - A comparison of the signal pathways between the TNF alpha- and oridonin-induced
      murine L929 fibrosarcoma cell death.
AB  - Oridonin, an active component isolated from Rabdosia rubescences, has been
      reported to have antitumor effects. In this study, we compared the signal
      transduction pathways between TNFalpha-and oridonin-induced L929 cell death.
      Oridonin and TNFalpha initiated apoptotic morphologic changes, but DNA
      fragmentation was found in TNFalpha-treated L929 cells but not in oridonin
      treated ones. The pan-caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD
      fmk) and caspase-3 inhibitor (z-DEVD-fmk) augmented oridonin-and TNFalpha-induced
      cell death. However, the caspase-9 inhibitor (z-LEHD-fmk) only increased oridonin
      induced L929 cell death. Moreover, poly (ADPribose) polymerase (PARP) was cleaved
      in oridonin-treated L929 cells but not in the TNFalpha-treated groups, and the
      caspase-3 inhibitor (z-DEVD-fmk) failed to inhibit PARP cleavage. These results
      showed that only oridonin-induced L929 cell death required PARP degradation in a
      caspase-3 independent manner. In addition, oridonin increased the ratio of
      Bax/Bcl-2 protein expression, but TNFalpha did not. TNFalpha induced p38 and ERK
      activation, whereas oridonin triggered only ERK activation. We also investigated
      the effect of oridonin on intracellular TNFalpha expression, and found that
      oridonin augmented endogenous pro-TNFalpha expression and its upstream protein
      IkB phosphorylation. These results indicated that although oridonin promoted
      endogenous pro-TNFalpha expression, a great difference existed between the signal
      pathways through which TNFalpha-and oridonin-induced cell death.

PMID- 16418770
TI  - The effects of interval length between sessions in a hypercholesterolemia
      education class.
AB  - This study focused on the effects of different intervals between sessions of a
      hypercholesterolemia education class on post-intervention outcomes. The same
      comprehensive group-programme contents on hypercholesterolemia were delivered
      either monthly (for 6 months) or twice-monthly (for 3 months) by the same
      teaching professionals in a community setting. The twice-monthly programme
      included 46 participants (male/female = 7/39, average age: 65.8 years)and the
      monthly programme consisted of 48(male/female = 9/39, age: 66.4). At the
      beginning of the study, all subjects belonged to the 'contemplation' stage of
      diet and exercise habits within the Transtheoretical Model of Change. The stage
      matched intervention helped many participants move to the 'action ' stage by 6
      months after the last session, especially in the twice-monthly group. The change
      rate of exercise from the 'contemplation' stage to the 'action' stage was
      significantly higher in the twice-monthly group (76.1 percent) than in the
      monthly (54.2 percent ). In both monthly and twice-monthly formats, participants'
      satisfaction and understanding levels at the end of the programme were high, but
      were significantly higher in the twice-monthly group. Through favorable
      lifestyles and higher levels of satisfaction and learning, the twice-monthly
      format may produce more positive results in cholesterol management than the
      monthly format, as the shorter period of time makes the programme more intensive.

PMID- 16418771
TI  - Intracavernous injection of prostaglandin E1 is effective in patients with
      erectile dysfunction not responding to phosphodiseterase 5 inhibitors.
AB  - We report on 64 patients who did not achieve erections adequate for satisfactory
      sexual intercourse from among a total of 243 patients who were prescribed PDE5
      inhibitors for erectile dysfunction (ED). Intracavernous injection (ICI) of PGE
      was performed in this non-responder group. An ICI of 20 or 40 mcg of PGE1 in 1 ml
      saline was performed and the responses evaluated. Forty-nine out of 64 (77
      percent ) cases responded to 20 mcg of PGE1. Forty mcg of PGE was injected into
      the 15 non-responding cases, and 9 patients responded favorably. The overall
      effective rate was 58/64 (91 percent ). No major adverse effects were observed.

PMID- 16418772
TI  - Abdominal wall and thigh abscess resulting from the penetration of ascending
      colon cancer.
AB  - An unusual case is described in which an abdominal wall and thigh abscess was an
      initial symptom of ascending colon cancer. A 76-year-old woman was referred to
      our hospital for investigation of fever and abdominal and thigh swelling.
      Computed tomography revealed a right abdominal wall, retroperitoneal, psoas and
      thigh abscess formation suspected to be caused by colon perforation. Due to the
      patient's poor general condition, local drainage of the abscess was performed on
      the following day of hospitalization. Histological examination of necrotic
      tissues removed form the retroperitoneal cavity demonstrated adenocarcinoma of
      the colon. The patient subsequently underwent right hemicolectomy with lymph
      nodal dissection after 19 days of the drainage procedure and was transferred to
      another hospital on the 49th day following the second surgery.

PMID- 16418774
TI  - Vascular biology and the skeleton.

PMID- 16418775
TI  - Human microvascular endothelial cell activation by IL-1 and TNF-alpha stimulates
      the adhesion and transendothelial migration of circulating human CD14+ monocytes
      that develop with RANKL into functional osteoclasts.
AB  - Circulating pre-OCs may be recruited to locally inflamed sites through specific
      interactions with activated microvasculature. We found that HMVECs stimulated the
      adhesion and TEM of circulating pre-OCs, in an ICAM-1- and CD44-dependent manner,
      leading to greater RANKL-induced OC formation and bone pit resorption.
      INTRODUCTION: Inflammation is critical for healing processes but causes severe
      tissue destruction when chronic. Local osteoclast (OC) formation and bone
      resorption may increase at inflammatory sites through multiple mechanisms,
      including direct stimulation by inflamed microvasculature of circulating OC
      precursor (pre-OC) migration through a blood vessel barrier into bone or joint
      tissue. How this might occur is not yet well understood. MATERIALS AND METHODS:
      Cytokine-activated human microvascular endothelial cell (HMVEC) monolayers, with
      or without IL-1 and TNF-alpha preactivation (24 h), were incubated in adhesion (1
      3 h) or porous transwell transendothelial migration (TEM; 3 h) assays with human
      peripheral blood mononuclear cells (hPBMCs) or CD14+ monocyte or CD14- lymphocyte
      subsets. The number of cells that adhered or transmigrated, and their ability to
      thereafter develop with macrophage-colony stimulating factor (M-CSF) + RANKL into
      bone pit-resorbing OCs, were analyzed. Immunostaining and neutralizing antibodies
      to key cell adhesion molecules were used to determine their potential involvement
      in stimulated CD14+ monocyte TEM. RESULTS: M-CSF + RANKL caused OC and bone pit
      formation only from hPBMCs and CD14+ cells but not CD14- cells. Adhesion of
      hPBMCs or CD14+ cells but not CD14- cells was stimulated by cytokine
      preactivation of HMVECs and led to the full capture of all circulating pre-OCs
      capable of developing into OCs. Cytokine-preactivated HMVECs also promoted the
      postadhesion TEM of hPBMCs and CD14+ populations, resulting in markedly greater
      OC formation and bone pit resorption by transmigrated cells. Immunodetectable
      vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM
      1), and CD44 levels increased on cytokine-treated HMVEC surfaces, and
      neutralizing antibodies to ICAM-1 or CD44, but not VCAM-1 or platelet endothelial
      cell adhesion molecule (PECAM-1), inhibited stimulated CD14+ cell TEM through
      activated HMVECs. CONCLUSIONS: This is the first demonstration that cytokine
      activated HMVECs efficiently capture and promote the TEM of circulating pre-OCs
      capable of differentiating into bone-resorbing OCs. Thus, direct pre-OC
      recruitment by activated microvasculature at inflammatory sites may significantly
      contribute to normal OC bone remodeling during fracture healing or exacerbate
      pathological bone loss in various chronic inflammatory disorders.

PMID- 16418776
TI  - Gorham-Stout syndrome: a monocyte-mediated cytokine propelled disease.
AB  - We studied the biological features and the immunophenotype of a cell culture
      established from the lesion of soft tissues of a woman affected by Gorham-Stout
      syndrome. We found that these cells belonged to a monocytic lineage with some
      characteristics of immature osteoclasts and were able to release large amounts of
      osteoclastogenic and angiogenic molecules that may contribute to disease
      progression. INTRODUCTION: Gorham-Stout syndrome is a rare disease characterized
      by osteolysis and proliferation of vascular or lymphatic vessels, with a severe
      outcome. Its etiology and the identification of the cell types involved are
      completely unknown. MATERIALS AND METHODS: A cell culture from a lesion of soft
      tissues was established, and its behavior in vitro and in immunodeficient mice
      was studied. We analyzed (1) the cell phenotype by flow cytometry; (2) the
      adhesive and migratory properties on different substrates; (3) the ability to
      differentiate into mature osteoclasts; (4) the production of osteclastogenic and
      angiogenic molecules; (5) the in vivo angiogenic activity of the cells
      subcutaneously implanted in mouse in a Matrigel plug; and (6) the ability to
      recapitulate the disease when transplanted in nude mice. RESULTS AND CONCLUSIONS:
      The established culture consisted of a morphologically homogeneous cell
      population belonging to a monocytic lineage having some features of an osteoclast
      like cell type. Cells had an invasive phenotype, were angiogenic, and produced
      osteoclastogenic (IL-6, TGF-beta1, IL-1beta) and angiogenic (vascular endothelial
      growth factor-A [VEGF-A], CXCL-8) molecules when challenged with inflammatory
      cytokines. Immunodeficient mice injected with these cells did not show any bone
      lesions or vascular alteration, but had high amounts of circulating human IL-6
      and VEGF-A. Cells isolated from a cutaneous lymphangiomatosis did not show any of
      these findings. These data suggest that cells of monocyte-macrophage lineage play
      an essential role in the pathogenesis of Gorham-Stout disease, whose progression
      is propelled by cytokine circuits that accelerate angiogenesis and
      osteoclastogenesis.

PMID- 16418777
TI  - Suppression of adjuvant-induced arthritic bone destruction by cyclooxygenase-2
      selective agents with and without inhibitory potency against carbonic anhydrase
      II.
AB  - In vitro assays revealed that COX-2 inhibitors with CA II inhibitory potency
      suppressed both differentiation and activity of osteoclasts, whereas that without
      the potency reduced only osteoclast differentiation. However, all COX-2
      inhibitors similarly suppressed bone destruction in adjuvant-induced arthritic
      rats, indicating that suppression of osteoclast differentiation is more effective
      than that of osteoclast activity for the treatment. INTRODUCTION: Cyclooxygenase
      (COX)-2 and carbonic anhydrase II (CA II) are known to play important roles in
      the differentiation of osteoclasts and the activity of mature osteoclasts,
      respectively. Because several COX-2 selective agents were recently found to
      possess an inhibitory potency against CA II, this study compared the bone sparing
      effects of COX-2 selective agents with and without the CA II inhibitory potency.
      MATERIALS AND METHODS: Osteoclast differentiation was determined by the mouse co
      culture system of osteoblasts and bone marrow cells, and mature osteoclast
      activity was measured by the pit area on a dentine slice resorbed by osteoclasts
      generated and isolated from bone marrow cells. In vivo effects on arthritic bone
      destruction were determined by radiological and histological analyses of hind
      paws of adjuvant-induced arthritic (AIA) rats. RESULTS: CA II was expressed
      predominantly in mature osteoclasts, but not in the precursors. CA II activity
      was inhibited by sulfonamide-type COX-2 selective agents celecoxib and JTE-522
      similarly to a CA II inhibitor acetazolamide, but not by a methylsulfone-type COX
      2 inhibitor rofecoxib. In vitro assays clearly revealed that celecoxib and JTE
      522 suppressed both differentiation and activity of osteoclasts, whereas
      rofecoxib and acetazolamide suppressed only osteoclast differentiation and
      activation, respectively. However, bone destruction in AIA rats was potently and
      similarly suppressed by all COX-2 selective agents whether with or without CA II
      inhibitory potency, although only moderately by acetazolamide. CONCLUSIONS:
      Suppression of osteoclast differentiation by COX-2 inhibition is more effective
      than suppression of mature osteoclast activity by CA II inhibition for the
      treatment of arthritic bone destruction.

PMID- 16418778
TI  - Human osteoblast precursors produce extracellular adenosine, which modulates
      their secretion of IL-6 and osteoprotegerin.
AB  - We showed that human osteoprogenitor cells produced adenosine and expressed ecto
      5'-nucleotidase and all four adenosine receptor subtypes. Adenosine stimulated IL
      6 but inhibited osteoprotegerin secretion, suggesting that adenosine is a newly
      described regulator of progenitor cell function. INTRODUCTION: Maintaining
      skeletal homeostasis relies on there being a balance between bone formation and
      resorption; an imbalance between these processes can lead to diseases such as
      osteoporosis and rheumatoid arthritis. Recent reports showed that locally
      produced ATP, acting through P2 receptors, has pronounced effects on bone
      formation. However, ATP can be enzymatically cleaved to adenosine that has little
      or no activity at P2 receptors but mediates its action through the P1 family of
      receptors. We studied whether adenosine may also have an important role in
      controlling bone cell differentiation and function. MATERIALS AND METHODS:
      Extracellular adenosine levels were analyzed by high-performance liquid
      chromatography in HCC1 and bone marrow stromal (BMS) cells. Ecto-5'-nucleotidase
      (CD73) expression and activity was determined by RT-PCR, immunocytochemistry, and
      the cleavage of etheno-AMP to ethenoadenosine. Adenosine receptor expression and
      activity were determined by RT-PCR and cAMP measurements. The effects of
      adenosine receptor agonists on IL-6, osteoprotegerin (OPG), and RANKL expression
      were determined by ELISA and QRT-PCR. RESULTS: HCC1 and BMS cells produce
      adenosine and express CD73 and all four adenosine receptor subtypes. The A2b
      receptor was shown to be functionally dominant in HCC1 cells, as determined by
      cAMP production and in its stimulation of IL-6 secretion. Adenosine receptor
      agonism also inhibited OPG secretion and OPG but not RANKL mRNA expression.
      CONCLUSIONS: Our findings show that HCC1 and primary BMS cells produce adenosine,
      express CD73 and all four adenosine receptor subtypes. In HCC1 cells, adenosine
      has a potent stimulatory action on IL-6 secretion but an inhibitory action on OPG
      expression. These data show for the first time that adenosine may be an important
      regulator of progenitor cell differentiation and hence an important local
      contributor to the regulation of bone formation and resorption.

PMID- 16418779
TI  - TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and
      function.
AB  - Deficiency of the signaling adapter protein DAP12 or its associated receptor
      TREM2 is associated with abnormal OC development in humans. Here we examine the
      role of TREM2 in mouse OC development and function, including migration and
      resorption in vitro. These results provide new evidence that TREM2 regulates OC
      function independent of its effects on multinucleated OC differentiation.
      INTRODUCTION: TREM2 (triggering receptor expressed in myeloid cells-2) associates
      with the signaling adapter DAP12 in osteoclasts (OCs). Genetic mutation or
      deletion of either the TYROBP (DAP12) or TREM2 gene is associated with the human
      disorder of brain and bone, Nasu-Hakola disease. We and others recently showed
      the critical requirement for immunoreceptor tyrosine-based activation motif
      (ITAM) signals through DAP12 and the Fc Receptor gamma chain (FcRgamma) during OC
      development. Here, we further define the role of TREM2 in OC differentiation and
      describe a role for TREM2 in OC migration and bone resorption. MATERIALS AND
      METHODS: We generated monoclonal anti-mouse TREM2 antibodies (mAb), analyzed pre
      osteoclasts and mature OCs for TREM2 surface expression, and determined the
      effect of antibody ligation on in vitro OC differentiation, resorption, and
      migration. TREM2 RNA interference (RNAi) was used to disrupt expression of TREM2
      in pre-osteoclasts. RESULTS: Using flow cytometry, our studies reveal that TREM2
      is weakly expressed on C57BL/6 bone marrow macrophages (BMMs) and is upregulated
      during culture with RANKL and macrophage-colony stimulating factor (M-CSF). The
      expression of TREM2 is unaltered in DAP12-deficient OCs. Using C57BL/6 BMMs or
      RAW264.7 precursors, anti-TREM2 mAb treatment with RANKL and M-CSF enhances the
      formation of multinuclear TRACP+ OCs compared with control mAb treatment. In
      contrast, these agents have no effect on DAP12-deficient precursors. Monoclonal
      Ab blockade of TREM2 on OCs generated from C57BL/6 BMMs results in decreased
      resorption of artificial calcium-phosphate substrate and dentine. Reduction of
      TREM2 expression in RAW264.7 cells by RNAi results in loss of OC formation in
      response to RANKL and M-CSF. Anti-TREM2 cross-linking enhances migration of
      C57BL/6 OCs and RAW246.7 OCs in response to M-CSF. CONCLUSIONS: Our studies
      indicate that the TREM2 receptor regulates OC multinucleation as well as
      resorption and migration of mature OCs. Thus, TREM2-DAP12 signals regulate both
      OC formation and function.

PMID- 16418780
TI  - JunB as a downstream mediator of PTHrP actions in cementoblasts.
AB  - The role of AP-1 family members in the action of PTHrP was examined in
      cementoblasts. PTHrP increased mRNA and protein levels of all Fos members, but
      only one Jun member (JunB) was increased. Overexpression of JunB in cementoblasts
      mimicked actions of PTHrP to support osteoclastogenesis and inhibit cementoblast
      differentiation, suggesting that the actions of PTHrP on mesenchymal cells
      operate through JunB. INTRODUCTION: Cementoblasts are mesenchymal cells that
      share phenotypic features with osteoblasts in vitro; however, unlike osteoblasts,
      cementoblasts rarely support osteoclastogenesis in vivo. The osteoblast-mediated
      support of osteoclastogenesis involves PTH-induced reduction in osteoprotegerin
      (OPG) expression. PTH acts on osteoblastic cells through specific signaling
      pathways and transcription factors such as activator protein 1 (AP-1). The
      purpose of this study was to determine the impact of PTH-related protein (PTHrP)
      on AP-1 transcription factors in cementoblasts and the role of JunB in the
      actions of PTHrP. MATERIALS AND METHODS: Cementoblastic cells were treated with
      PTHrP and evaluated for mRNA and protein levels of AP-1 family members. Stable
      transfectants of OCCM cells overexpressing JunB were evaluated for OPG
      production, ability to support osteoclastogenesis, and measures of proliferation
      and differentiation. RESULTS: PTHrP treatment in vitro resulted in a time
      dependent upregulation of mRNA and proteins for the Fos family members, but only
      JunB of the Jun family. OPG mRNA and protein levels were reduced by PTHrP in OCCM
      and were lower in JunB overexpressing cells than controls. In co-culture
      experiments, TRACP+ cells were increased with RANKL treatment in JunB
      overexpressing cells compared with controls. Cementoblast differentiation was
      reduced with overexpression of JunB as measured by a decrease in mineralized
      nodule formation and gene expression for bone sialoprotein and osterix. Measures
      of proliferation including cell number and cyclin D1 levels were increased in
      JunB overexpressing clones. In vivo, cementoblast implants exhibited a
      cementoblastoid nature with copious mineral-like matrix, whereas JunB
      overexpressing implants were densely cellular with little mineralized matrix.
      CONCLUSIONS: JunB was the only Jun family member increased by PTHrP, and its
      overexpression showed similar patterns of gene expression and OPG production as
      PTHrP treatment of controls. These data suggest that JunB may be a key mediator
      of PTHrP actions in cementoblasts.

PMID- 16418781
TI  - Low protein intake is associated with impaired titanium implant osseointegration.
AB  - Low protein intake is highly prevalent among orthopaedic elderly patients. We
      studied the effects of an isocaloric low protein diet on the resistance to pull
      out of titanium rods implanted into rats proximal tibia. Isocaloric low protein
      intake impairs titanium implant osseointegration, with a decreased strength
      needed to completely loose the implant and altered bone microarchitecture in its
      vicinity. INTRODUCTION: Low protein intake is highly prevalent among elderly
      patients in orthopaedic wards and could retard fracture healing. It was
      previously shown that reduced protein intake decreases bone strength. Whether
      dietary protein intake could influence titanium implant osseointegration is
      unknown. We studied the effects of an isocaloric low protein diet on the
      resistance to pull-out of titanium rods implanted into rats proximal tibia.
      MATERIALS AND METHODS: Forty-eight 11-month-old female rats were fed isocaloric
      diets containing 2.5% (low protein) or 15% (normal protein) casein from 2 weeks
      before the implantation of a 1-mm-diameter cylindrical titanium rod in the
      proximal metaphysis of each tibia. Four, 6, and 8 weeks after implantation, the
      tibias were removed for microCT histomorphometry to quantify bone-to-implant
      contact and bone trabecular microarchitecture around the implant. Resistance to
      implant pull-out was tested by recording the maximal force necessary to
      completely loosen the implant. RESULTS: Pull-out strength was significantly lower
      in rats fed an isocaloric low protein diet by 6 and 8 weeks after implantation (
      43%, p < 0.001 and -42%, p < 0.001, respectively) compared with rats fed a normal
      protein diet. Bone-to-implant contact was significantly lower in the low protein
      group 8 weeks after implantation (p < 0.05). Bone-to-implant contact and pull-out
      strength were correlated (r2= 0.57, p < 0.0001). BV/TV around the implant was
      19.9 +/- 2.2% (SE) versus 31.8 +/- 3.3% (p < 0.05) at 6 weeks and 20.1 +/- 1.9%
      versus 29.8 +/- 3.2% (p < 0.05) at 8 weeks after implantation in the low protein
      and normal protein intake groups, respectively. Trabecular thickness was 96.2 +/-
      3.7 versus 113.0 +/- 3.6 microm (p < 0.01) at 6 weeks and 101.4 +/- 2.7 versus
      116.2 +/- 3.3 microm (p < 0.01) at 8 weeks in the corresponding groups. In a
      structure model index analysis, there was a significant shift to a more rod-like
      pattern in the low protein diet groups. All these changes were associated with
      lower plasma IGF-I levels. CONCLUSIONS: Isocaloric low protein intake impairs
      titanium implant osseointegration, with decreased strength needed to completely
      loosen the implant and altered bone microarchitecture in the vicinity of the
      implant.

PMID- 16418782
TI  - Association of functionally different RUNX2 P2 promoter alleles with BMD.
AB  - RUNX2 gene SNPs were genotyped in subjects from the upper and lower deciles of
      age- and weight-adjusted femoral neck BMD. Of 16 SNPs in RUNX2 and its two
      promoters (P1 and P2), only SNPs in the P2 promoter were significantly associated
      with BMD. These P2 promoter SNPs were functionally different in gel-shift and
      promoter activity assays. INTRODUCTION: Specific osteoblast genes are induced by
      Runx2, a cell-specific transcription factor that is a candidate gene for
      controlling BMD. We tested the hypothesis that RUNX2 genetic variation is
      associated with BMD. MATERIALS AND METHODS: From a population repository of
      normal subjects, the age- and weight-adjusted femoral neck BMD was ranked, and
      the upper and lower deciles (n = 132 each) were taken to represent the adjusted
      extremes of the population distribution. In these 264 subjects, we identified 16
      allelic variations within the RUNX2 gene and promoters (P1 and P2) through DNA
      sequencing and denaturing high-performance liquid chromatography.
      Characterization of these alleles was performed through allele-specific cloning,
      transfection into ROS 17/2.8 cells, luciferase reporter analysis, and
      electrophoretic mobility shift assays. RESULTS: Within the P2 promoter were three
      polymorphic nucleotides for which the minor alleles were over-represented in the
      upper decile of BMD (0.117 and 0.064 in the upper and lower deciles,
      respectively). These alleles are in near complete linkage disequilibrium with
      each other and represent a haplotype block that is significantly associated with
      increased BMD. The common and rare P2 promoter alleles were cloned upstream of
      luciferase, and when transfected into osteoblast-like cells, the construct
      representing the rare haplotype showed significantly greater P2 promoter activity
      than the common haplotype. CONCLUSIONS: Because the high BMD allele had higher P2
      promoter activity, the data suggest that greater RUNX2 P2 promoter activity is
      associated with higher BMD.

PMID- 16418783
TI  - Effects of cyclic versus daily hPTH(1-34) regimens on bone strength in
      association with BMD, biochemical markers, and bone structure in mice.
AB  - We developed a cyclic PTH regimen with repeated cycles of 1-week on and off daily
      PTH injection and explored its effects on bone strength, BMD, bone markers, and
      bone structure in mice. Cyclic protocols produced 60-85% of the effects achieved
      by daily protocols with 57% of the total PTH given, indicating more economic use
      of PTH. The study supports further exploration of cyclic PTH regimens for the
      treatment of osteoporosis. INTRODUCTION: To minimize the cost and the catabolic
      action of hPTH(1-34), a cyclic PTH regimen with repeated 3-month cycles of on-and
      off daily injection of hPTH(1-34) was developed in humans and shown to be as
      effective as a daily regimen in increasing vertebral BMD. However, changes in BMD
      may not adequately predict changes in bone strength. A murine model was developed
      to explore the efficacy of a cyclic PTH regimen on bone strength in association
      with other bone variables. MATERIALS AND METHODS: Twenty-week-old, intact, female
      C57BL/J6 mice (n = 7/group) were treated with (1) daily injection with vehicle
      for 7 weeks (control); (2) daily injection with hPTH(1-34) (40 microg/kg/day) for
      7 weeks (daily PTH); and (3) daily injection with hPTH(1-34) and vehicle
      alternating weekly for 7 weeks (cyclic PTH). BMD was measured weekly by DXA, and
      serum bone markers, bone structure, and strength were measured at 7 weeks.
      RESULTS: Daily and cyclic PTH regimens increased BMD at all sites by 16-17% and 9
      12%, respectively (all p < 0.01). The most dramatic effect of cyclic PTH occurred
      during the second week of treatment when PTH was off, with femoral and tibial BMD
      continuing to increase to the same extent as that produced by daily PTH. Both
      daily and cyclic PTH regimens significantly increased osteocalcin (daily, 330%;
      cyclic, 260%), mTRACP (daily, 145%; cyclic, 70%), femoral cortical width (daily,
      23%; cyclic, 13%), periosteal circumference (daily, 5%; cyclic, 3.5%), and bone
      strength (max load: daily, 48%; cyclic, 28%; energy absorbed: daily, 103%;
      cyclic, 61%), respectively. Femoral bone strength was positively correlated with
      BMD, bone markers, and cortical structure. Neither regimen had an effect on
      vertebral bone strength. Although actual effects of cyclic PTH were 60-85% of
      those produced by daily PTH, the effects of cyclic PTH per unit amount
      administered were slightly greater than those of daily PTH for most measures.
      CONCLUSIONS: PTH-enhanced femoral bone strength is positively correlated with its
      effects on femoral BMD, bone markers, and bone structure. Cyclic PTH regimens
      represent a potential economic use of PTH and warrant further study.

PMID- 16418784
TI  - Effect of teriparatide [rhPTH(1-34)] on BMD when given to postmenopausal women
      receiving hormone replacement therapy.
AB  - The effects of teriparatide when given in combination with HRT were studied in
      postmenopausal women with low bone mass or osteoporosis. The data provide
      evidence that the adverse event profile for combination therapy with teriparatide
      + HRT together is consistent with that expected for each treatment alone and that
      the BMD response is greater than for HRT alone. INTRODUCTION: Teriparatide
      [rhPTH(1-34)], given as a once-daily injection, activates new bone formation in
      patients with osteoporosis. Hormone replacement therapy (HRT) prevents
      osteoporosis by reducing bone resorption and formation. Combination therapy with
      these two compounds, in small clinical trials, increased BMD and reduced
      vertebral fracture burden. The purpose of this study was to determine whether
      teriparatide provided additional effect on BMD when given in combination with
      HRT. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled study
      was conducted in postmenopausal women with either low bone mass or osteoporosis.
      Patients were randomized to placebo subcutaneous plus HRT (n = 125) or
      teriparatide 40 microg/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median
      treatment exposure of 13.8 months. Approximately one-half of the patients in each
      group were pretreated with HRT for at least 12 months before randomization.
      Patients received 1000 mg calcium and 400-1200 IU of vitamin D daily as oral
      supplementation. BMD was measured by DXA. RESULTS: Compared with HRT alone,
      TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus
      3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study
      endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one
      third distal radius was lower, in the combination therapy but not in the HRT
      group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were
      increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared
      with HRT. A similar profile of BMD and bone markers was evident in both
      randomized patients as well as in subgroups of patients not pretreated or
      pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg
      cramps were more frequently reported in the TPTD40 + HRT group. CONCLUSIONS:
      Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent,
      provides additional increases in BMD beyond that provided by HRT alone. The
      adverse effects of teriparatide when added to HRT were similar to the adverse
      effects described for teriparatide administered alone. Whether teriparatide was
      initiated at the same time as HRT or after at least 1 year on HRT, the
      incremental increases over HRT alone were similar.

PMID- 16418785
TI  - Pretreatment levels of bone turnover and the antifracture efficacy of
      alendronate: the fracture intervention trial.
AB  - The influence of pretreatment bone turnover on alendronate efficacy is not known.
      In the FIT, we examined the effect of pretreatment bone turnover on the
      antifracture efficacy of daily alendronate given to postmenopausal women. The
      nonspine fracture efficacy of alendronate was significantly greater among both
      osteoporotic and nonosteoporotic women with higher baseline levels of the bone
      formation marker PINP. INTRODUCTION: Previous trials have shown that high bone
      turnover is associated with greater increases in BMD among bisphosphonate-treated
      women. The influence of pretreatment bone turnover levels on antifracture
      efficacy has not been well studied. MATERIALS AND METHODS: We randomized women 55
      80 years of age with femoral neck BMD T scores < or = -1.6 to alendronate (ALN),
      5-10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were
      osteoporotic (femoral neck BMD T score < or = -2.5 or prevalent vertebral
      fracture), and 2689 were not osteoporotic (BMD T score > -2.5 and no prevalent
      vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase
      (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross
      linked telopeptide of type 1 collagen (sCTx) were measured in all participants
      using archived serum (20% fasting). The risk of incident spine and nonspine
      fracture was compared in ALN- and PBO-treated subjects stratified into tertiles
      of baseline bone marker level. RESULTS AND CONCLUSIONS: During a mean follow-up
      of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were
      documented. Compared with placebo, the reduction in nonspine fractures with ALN
      treatment differed significantly among those with low, intermediate, and high
      pretreatment levels of PINP levels (p = 0.03 for trend). For example, among
      osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the
      ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65,
      1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in
      the highest tertile of PINP (>56.8 ng/ml). Results were similar among women
      without osteoporosis at baseline. Although they did not reach statistical
      significance, similar trends were observed with baseline levels of BSALP.
      Conversely, spine fracture treatment efficacy among osteoporotic women did not
      differ significantly according to pretreatment marker levels. Spine fracture
      treatment efficacy among nonosteoporotic women was related to baseline BSALP (p =
      0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater
      among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If
      confirmed in other studies, these findings suggest that bisphosphonate treatment
      may be most effective in women with elevated bone turnover.

PMID- 16418786
TI  - Effects of oral alendronate on BMD in adult patients with osteogenesis
      imperfecta: a 3-year randomized placebo-controlled trial.
AB  - A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect
      of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta.
      The mean increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7
      +/- 5.7% in the alendronate and placebo groups, respectively. Oral alendronate
      increases BMD in adult patients with osteogenesis imperfecta. INTRODUCTION: This
      study evaluated the effect of oral alendronate on the BMD of adult patients with
      osteogenesis imperfecta. MATERIALS AND METHODS: We carried out a 3-year,
      randomized, double-blind, placebo-controlled trial of oral alendronate in 64
      adult patients with osteogenesis imperfecta. The primary endpoint was the
      difference between the groups in the mean percent change in lumbar spine BMD at 3
      years. Secondary outcomes included changes in BMD of total hip, vertebral and
      peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical
      markers. Patients were treated daily with either placebo or 10 mg alendronate.
      All received 1 g of calcium and 800 IU of vitamin D daily. RESULTS: The mean +/-
      SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/-
      5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in
      the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo
      group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect
      of alendronate on fracture rate. A significant increase of the pain score was
      noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not
      in the per protocol analysis. There was no change in hearing in either group.
      Bone resorption and formation biochemical markers were significantly decreased in
      the alendronate group (p < 0.001). There were no differences in severe adverse
      effects between the groups, but there was an increase in nonsevere upper
      gastrointestinal effects in the alendronate group (p = 0.003). CONCLUSIONS: Oral
      alendronate increases BMD and increase nonsevere gastrointestinal adverse effects
      but does not modify the hearing loss in adult patients with osteogenesis
      imperfecta. More studies are needed to evaluate an effect on the fracture rate.

PMID- 16418787
TI  - Cortical and trabecular load sharing in the human vertebral body.
AB  - The biomechanical role of the vertebral cortical shell remains poorly understood.
      Using high-resolution finite element modeling of a cohort of elderly vertebrae,
      we found that the biomechanical role of the shell can be substantial and that the
      load sharing between the cortical and trabecular bone is complex. As a result, a
      more integrative measure of the trabecular and cortical bone should improve
      noninvasive assessment of fracture risk and treatments. INTRODUCTION: A
      fundamental but poorly understood issue in the assessment of both osteoporotic
      vertebral fracture risk and effects of treatment is the role of the trabecular
      bone and cortical shell in the load-carrying capacity of the vertebral body.
      MATERIALS AND METHODS: High-resolution microCT-based finite element models were
      developed for 13 elderly human vertebrae (age range: 54-87 years; 74.6 +/- 9.4
      years), and parameter studies-with and without endplates-were performed to
      determine the role of the shell versus trabecular bone and the effect of model
      assumptions. RESULTS: Across vertebrae, whereas the average thickness of the
      cortical shell was only 0.38 +/- 0.06 mm, the shell mass fraction (shell
      mass/total bone mass)-not including the endplates-ranged from 0.21 to 0.39. The
      maximum load fraction taken by the shell varied from 0.38 to 0.54 across
      vertebrae and occurred at the narrowest section. The maximum load fraction taken
      by the trabecular bone varied from 0.76 to 0.89 across vertebrae and occurred
      near the endplates. Neither the maximum shell load fraction nor the maximum
      trabecular load fraction depended on any of the densitometric or morphologic
      properties of the vertebra, indicating the complex nature of the load sharing
      mechanism. The variation of the shell load-carrying capacity across vertebrae was
      significantly altered by the removal of endplates, although these models captured
      the overall trend within a vertebra. CONCLUSIONS: The biomechanical role of the
      thin cortical shell in the vertebral body can be substantial, being about 45% at
      the midtransverse section but as low as 15% close to the endplates. As a result
      of the complexity of load sharing, sampling of only midsection trabecular bone as
      a strength surrogate misses important biomechanical information. A more
      integrative approach that combines the structural role of both cortical and
      trabecular bone should improve noninvasive assessment of vertebral bone strength
      in vivo.

PMID- 16418788
TI  - Population-based analysis of the relationship of whole bone strength indices and
      fall-related loads to age- and sex-specific patterns of hip and wrist fractures.
AB  - In an age- and sex-stratified population sample (n = 700), we estimated fall
      related loads and bone strength indices at the UDR and FN. These load/strength
      ratios more closely simulated patterns of wrist and hip fractures occurring in
      the same population than did measurement of vBMD. INTRODUCTION: Areal BMD
      measurements, although associated with fracture risk, incompletely explain
      patterns of fragility fractures. Moreover, population-based assessments relating
      applied loads and whole bone strength to fracture patterns have not been made.
      MATERIALS AND METHODS: Using QCT, we assessed volumetric BMD (vBMD), cross
      sectional geometry, and axial (EA) and flexural (EI) rigidities (indices of
      bone's resistance to compressive and bending loads, respectively) at the
      ultradistal radius (UDR) and femoral neck (FN) and estimated the loads applied to
      the wrist and hip during a fall. We used fall load (FL)/bone strength ratios to
      estimate fracture risk. RESULTS: vBMD in young adults was similar between sexes.
      Decreases in vBMD over life were also similar (30% and 28%) at UDR but were
      somewhat greater (46% and 34%) at FN in women versus men, respectively. In young
      adults, FL/strength ratios at UDR were 32-51% lower (better) in men than in women
      and increased (worsened) over life less in men (+4% to +22%) than in women (+20%
      to +33%). In young adults, FL/strength ratios at FN were only marginally better
      in men than in women but worsened less over life in men (+22% to +36%) than in
      women (+40% to +62%). CONCLUSIONS: The 6:1 female preponderance and the virtual
      immunity of men for age-related increases in wrist fractures are largely
      explained by the more favorable FL/strength ratios at UDR in young adult men
      (because of larger bone size and more favorable geometry) versus women and to
      maintaining this advantage over life. The 2-fold lower incidence of hip fractures
      in men versus women is largely explained by age-related increases (worsening) of
      FL/bone strength ratios that are only one-half of the increases in women. The
      moderate increases in these ratios with aging are insufficient to explain the >4
      fold increase in hip fracture incidence after age 75 in both sexes, suggesting
      contributions of other factors, especially the well-documented increased
      frequency of injurious falls among the elderly.

PMID- 16418789
TI  - Effect of age-related chronic immobility on markers of bone turnover.
AB  - The effects of acute immobilization on bone turnover are well known, but the
      effects of chronic hypomobility with aging have not been studied. In a cohort of
      1064 frail elderly subjects, immobility was significantly associated with serum
      PINP but not serum CTx after adjusting for confounders. The effect of immobility
      may be more marked on bone formation than on bone resorption. INTRODUCTION:
      Accelerated bone turnover and rapid bone loss caused by acute immobilization is
      well recognized, but the effects of age-related chronic reduction in mobility on
      bone turnover have been less well studied. We assessed the associations between
      bone turnover and measures of mobility in a cohort of elderly subjects. MATERIALS
      AND METHODS: We measured serum levels of the aminoterminal propeptide of type I
      collagen (PINP), a marker of bone formation, and serum concentrations of the
      carboxyterminal telopeptide of type I collagen (CTx), a marker of bone
      resorption, as well as serum intact PTH, serum 25 hydroxyvitamin D (25OHD),
      mobility, and static balance in a well-characterized sample of 1064 elderly men
      and women living in residential aged care facilities. Serum creatinine,
      phosphate, albumin, and calcium were measured in a randomly selected subgroup of
      447 subjects. RESULTS: The subjects were elderly and frail; their mean age was
      86.0 years (range, 65-101 years); 69% used a walking aid; and 77% were vitamin D
      deficient (serum 25OHD level < 39 nM). Both serum PINP and CTx increased with age
      in both sexes. Elevated PINP or CTx was significantly correlated with high PTH,
      creatinine, and albumin in both genders, except for albumin in women. Age- and
      gender-adjusted serum CTx and PINP were significantly higher in those with poorer
      mobility and those with worse static balance. In multivariate analyses, higher
      serum PINP but not CTx was associated with poorer mobility and worse static
      balance. CONCLUSIONS: Our findings suggest that poor mobility contributes to the
      state of accelerated bone turnover usually seen in the elderly. The effect of
      chronic relative immobility may be more marked on bone formation than bone
      resorption.

PMID- 16418790
TI  - Polymorphisms in the aromatase gene predict areal BMD as a result of affected
      cortical bone size: the GOOD study.
AB  - The association between aromatase gene polymorphisms, bone parameters, and sex
      steroid levels was studied in 1068 men (18.9 +/- 0.6 years of age). Several
      aromatase gene polymorphisms were found to be associated with serum testosterone
      levels and cortical bone size but not with trabecular volumetric BMD.
      INTRODUCTION: Both testosterone and estrogens are important for the male
      skeleton. Aromatase, the product of the CYP19 gene, is the key enzyme in the
      conversion of testosterone to estradiol. A functional aromatase enzyme has been
      shown to be crucial for the normal development of the male skeleton. The role of
      genetic polymorphisms in the aromatase gene for trabecular volumetric BMD (vBMD)
      and cortical bone size has not previously been studied in men. MATERIALS AND
      METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study
      consists of 1068 men (18.9 +/- 0.6 years of age). The TTTA repeat polymorphism
      (TTTAn) and three single nucleotide polymorphisms (SNPs), including the Val80
      SNP, in the CYP19 gene, were analyzed. Serum levels of testosterone and estradiol
      were measured. Areal BMD (aBMD) was measured by DXA, whereas cortical and
      trabecular vBMD and cortical bone size were measured by pQCT. RESULTS: The TTTAn
      and the Val80 genotypes were independent predictors of aBMD of the radius, lumbar
      spine, total body, and cortical bone size (cortical cross-sectional area and
      thickness) of both the radius and tibia. In contrast, trabecular vBMD was not
      associated with CYP19 polymorphisms. Homozygosity for the long allele (>9
      repeats) of the TTTAn and for the G allele of the Val80 SNP was associated with
      the highest aBMD and testosterone levels as well as with the greatest cortical
      bone size. Regression analyses indicated that the association with aBMD was
      mediated through affected cortical bone size. CONCLUSIONS: We showed, in a large
      well-characterized cohort of men at the age of peak bone mass, that several
      common aromatase polymorphisms are associated with cortical bone size but not
      with trabecular vBMD. One may speculate that affected CYP19 activity, resulting
      in altered testosterone levels during pubertal development, might contribute to
      the association between CYP19 polymorphisms and cortical bone size.

PMID- 16418792
TI  - Two isocitrate dehydrogenases from a psychrophilic bacterium, Colwellia
      psychrerythraea.
AB  - Two structurally different monomeric and dimeric types of isocitrate
      dehydrogenase (IDH; EC 1.1.1.42) isozymes were confirmed to exist in a
      psychrophilic bacterium, Colwellia psychrerythraea, by Western blot analysis and
      the genes encoding them were cloned and sequenced. Open reading frames of the
      genes (icd-M and icd-D) encoding the monomeric and dimeric IDHs of this
      bacterium, IDH-M and IDH-D, were 2,232 and 1,251 bp in length and corresponded to
      polypeptides composed of 743 and 416 amino acids, respectively. The deduced amino
      acid sequences of the IDH-M and IDH-D showed high homology with those of
      monomeric and dimeric IDHs from other bacteria, respectively. Although the two
      genes were located in tandem, icd-M then icd-D, on the chromosomal DNA, a
      Northern blot analysis and primer extension experiment revealed that they are
      transcribed independent of each other. The expression of the monomeric and
      dimeric IDH isozyme genes in C. maris, a psychrophilic bacterium of the same
      genus as C. psychrerythraea, is known to be induced by low temperature and
      acetate, respectively, but no such induction in the expression of the C.
      psychrerythraea icd-M and icd-D genes was detected. IDH-M and IDH-D overexpressed
      in Escherichia coli were purified and characterized. In C. psychrerythraea, the
      IDH-M isozyme is cold-active whereas IDH-D is mesophilic, which is similar to C.
      maris that contains both cold-adapted and mesophilic isozymes of IDH. Experiments
      with chimeric enzymes between the cold-adapted monomeric IDHs of C.
      psychrerythraea and C. maris (IDH-M and ICD-II, respectively) suggested that the
      C-terminal region of the C. maris IDH-II is involved in its catalytic activity.

PMID- 16418794
TI  - Rigid sigmoidoscopy: a potential hazard for cross-contamination.
AB  - BACKGROUND: Rigid sigmoidoscopy using a disposable or nondisposable sigmoidoscope
      is a common outpatient procedure. It has been assumed that the nondisposable
      bellows and light head of the sigmoidoscope remain free from enteric organisms so
      that the procedure is sterile if a disposable or nondisposable (metal)
      sigmoidoscope shaft is used. The aim of this study was to identify the presence
      of organisms within the bellows or light head of the sigmoidoscope. METHODS: Of
      21 patients undergoing rigid sigmoidoscopy with a disposable instrument,
      bacterial cultures were taken from the inside of sterile Jackson-Pratt bulbs in
      12 patients, with the bulbs being used to simulate the nondisposable insufflation
      bellows. In an additional nine patients, swabs were taken for culture from the
      inside of the nondisposable light head. RESULTS: Enteric gram-negative
      Escherichia coli and mixed anaerobic organisms were cultured from the Jackson
      Pratt bulbs in two cases, and gram-positive organisms were cultured in another
      case. Gram-negative organisms, including Bacillus, Proteus mirabilis, Klebsiella,
      and Enterococcus faecalis, were cultured from the inside of the light head in two
      cases. CONCLUSION: Sigmoidoscopy using a disposable instrument is not a sterile
      procedure and may pose a risk of patient-to-patient cross-contamination by
      potentially harboring organisms in the bellows or light head.

PMID- 16418793
TI  - Recent developments in the thermophilic microbiology of deep-sea hydrothermal
      vents.
AB  - The diversity of thermophilic prokaryotes inhabiting deep-sea hot vents was
      actively studied over the last two decades. The ever growing interest is
      reflected in the exponentially increasing number of novel thermophilic genera
      described. The goal of this paper is to survey the progress in this field made in
      the years 2000-2005. In this period, representatives of several new taxa of
      hyperthermophilic archaea were obtained from deep-sea environments. Two of these
      isolates had phenotypic features new for this group of organisms: the presence of
      an outer cell membrane (the genus Ignicoccus) and the ability to grow
      anaerobically with acetate and ferric iron (the genus Geoglobus). Also, our
      knowledge on the diversity of thermophilic bacteria from deep-sea thermal
      environments extended significantly. The new bacterial isolates represented
      diverse bacterial divisions: the phylum Aquificae, the subclass
      Epsilonproteobacteria, the order Thermotogales, the families
      Thermodesulfobacteriaceae, Deferribacteraceae, and Thermaceae, and a novel
      bacterial phylum represented by the genus Caldithrix. Most of these isolates are
      obligate or facultative lithotrophs, oxidizing molecular hydrogen in the course
      of different types of anaerobic respiration or microaerobic growth. The existence
      and significant ecological role of some of new bacterial thermophilic isolates
      was initially established by molecular methods.

PMID- 16418795
TI  - The physiological changes of cumulative hemorrhagic shock in conscious rats.
AB  - Hemorrhagic shock is a common cause of death in emergency rooms. Current animal
      models of hemorrhage encounter a major problem that the volume and the rate of
      blood loss cannot be controlled. In addition, the use of anesthesia obscures
      physiological responses. Our experiments were designed to establish an animal
      model based on the clinical situation for studying hemorrhagic shock. Hemorrhagic
      shock was induced by withdrawing blood from a femoral arterial catheter. The
      blood volume withdrawn was 40% of the total blood volume for group 1 and 30% for
      group 2 and 3. Group 3 was anesthetized with sodium pentobarbital (25 mg/kg,
      i.v.) at the beginning of blood withdrawal. Our data showed that the survival
      rate was 87.5% at 48 h in the conscious group and 0% at 9 h in anesthetic group
      after hemorrhage. The levels of mean arterial pressure, heart rate, white blood
      count, TNF-alpha, IL1-beta, CPK, and LDH after blood withdrawal in the anesthetic
      group were generally lower than those in conscious groups. These results
      indicated that anesthetics significantly affected the physiology of experimental
      animals. The conscious, unrestrained and cumulative volume-controlled hemorrhagic
      shock model was a good experimental model to investigate the physical phenomenon
      without anesthetic interfernce.

PMID- 16418796
TI  - Breast cancer and long-term hormonal treatment of male hypogonadism.
AB  - Breast cancer in men is rare and its etiology is multifactorial. Androgens may
      promote the development of breast carcinoma in men though data on the subject is
      scarce. We observed 45 men with hypergonadotropic hypogonadism (aged 18-57) who
      received 250 mg of testosterone esters (Omnadren 250, Jelfa, Poland) every 3-4
      weeks for 5-26 years. Seventeen of them were treated for more than 10 years.
      During the observation period breast cancer was diagnosed in 2 subjects (11% of
      the followed men). In one case it occurred after 11 years and in the other after
      15 years of the therapy. We point to a possible association between long-term
      androgen replacement and a risk of breast cancer in men.

PMID- 16418797
TI  - Presentation of interleukin-12/-23 receptor beta1 deficiency with various
      clinical symptoms of Salmonella infections.
AB  - Clinical disease caused by weakly pathogenic mycobacterial species, Mycobacterium
      bovis Bacille Calmette-Guerin (BCG) and non-tuberculous environmental
      mycobacteria (EM), which is known as Mendelian susceptibility to mycobacterial
      disease (MSMD), is a rare entity defined recently. Infections with the more
      virulent Mycobacterium species, M. tuberculosis, may have largely gone unnoticed
      in these patients due to early death. Mutations in five proteins (IFNgammaR1,
      IFNgammaR2, IL-12/IL-23Rbeta1, IL-12/IL-23p40 and STAT1) have been found in MSMD.
      These patients are prone to surprisingly few other infectious diseases mainly to
      salmonellosis. Here we present three IL-12/IL-23Rbeta1 deficient patients from
      three different families and with different genetic mutations, who presented
      exclusively with Salmonella infections. Bacteremia and lymph node involvement
      were common clinical expressions. Leukocytoclastic vasculitis developed in one of
      these patients. Two patients were not inoculated with BCG, the third patient did
      not develop BCG infection although BCG vaccine had been given twice at ages of 1
      and 7 years. All three patients responded well to antibiotic treatment. In
      conclusion, patients with chronic, recurrent or complicated Salmonella infections
      should be screened for MSMD, particularly for IL-12/IL-23p40/IL-12R/-23Rbeta1
      deficiency. Conversely, in patients with genetic IL-12/-23Rbeta1 deficiency a
      full evaluation for Salmonella infection is required. IL-12/IL-23p40/IL-12R/IL
      23Rbeta1 deficiency seem to be underdiagnosed in patients with salmonellosis, and
      since such patients need prolonged therapy, diagnosis is important.

PMID- 16418798
TI  - Infants presenting with recurrent infections and low immunoglobulins:
      characteristics and analysis of normalization.
AB  - To better characterize infants presenting with diminished immunoglobulin levels
      and intact antibody formation, we present 49 such infants, correlating presenting
      characteristics with history and time to immunoglobulin normalization. Term
      infants with the following characteristics were included: 1) one or more
      immunoglobulin classes > 2SD below mean, 2) protective antibody titer to tetanus
      and diphtheria, 3) intact cellular immunity, 4) no features of other syndromes.
      The children were 69.4% male and had recurrent otitis media (77.6%), wheezing
      (61.2%), and atopy (26.5%). Diminished IgA (95.9%) was most common, but 65.3% had
      multiple isotypes diminished. During follow-up, 25/49 (51%) normalized
      immunoglobulins, of whom 80% were male; only 48% normalized in infancy. Female
      immunoglobulin normalization was significantly delayed (p < .001). No deaths or
      serious infections occurred. This phenotype is predominantly seen in male infants
      with otitis media and wheezing. Female infants have significantly delayed
      immunoglobulin normalization. Transient hypogammaglobulinemia of infancy can be
      diagnosed only retrospectively.

PMID- 16418799
TI  - CD166 expression, characterization, and localization in salivary epithelium:
      implications for function during sialoadenitis.
AB  - CD166 is an Ig superfamily molecule that binds homotypically to itself and
      heterotypically to CD6. Interactions between CD6 and CD166 are important during
      immune development and in alloreactivity. CD166 is expressed at increased levels
      in selected cancers and in rheumatoid arthritis synovium. Knowledge that CD166
      was expressed in normal human salivary epithelium led to these studies of CD166
      and CD6 in diseased mouse salivary glands, that resemble pathology seen in the
      human disease, Sjogren's syndrome. We showed that in mouse salivary epithelium
      CD166 was expressed but that expression of CD166 did not necessarily predict its
      function. Recombinant soluble CD6-Ig bound to CD6 ligands (CD6L) on transformed
      and freshly isolated salivary epithelial cells. Cross-blocking studies showed
      that binding of CD6-Ig to salivary epithelium was in part dependent on CD166, but
      that CD6-Ig binding may also involve additional CD6L. Binding of CD6-Ig was
      sensitive to trypsin digestion but resistant to digestion by collagenase and
      sialidase. Anti-CD166 ab precipitated CD166 from salivary epithelium pre- and
      post-treatment with the pro-inflammatory cytokine IFN-gamma. In contrast CD6-Ig
      only precipitated CD166 from IFN-gamma treated cells. More extensive
      colocalization between CD166 and the actin cytoskeleton was observed in
      sialoadenitis epithelium compared to control. We conclude that during
      sialoadenitis, CD166 undergoes a gain of function, resulting in closer
      association with the actin cytoskeleton and increased capacity to bind CD6. We
      suggest that altered CD166 function may contribute to the pro-inflammatory milieu
      during sialoadenitis seen in Sjogren's syndrome.

PMID- 16418800
TI  - Transduction of primary lymphocytes with Epstein-Barr virus (EBV) latent membrane
      protein-specific T-cell receptor induces lysis of virus-infected cells: A novel
      strategy for the treatment of Hodgkin's disease and nasopharyngeal carcinoma.
AB  - Adoptive immunotherapy with in vitro expanded cytotoxic T lymphocytes specific
      for Epstein-Barr virus (EBV) can successfully treat post-transplant
      lymphoproliferative disease (PTLD). However, extension of a similar strategy to
      Hodgkin's disease (HD) and nasopharyngeal carcinoma (NPC) is limited by the poor
      immunogenicity of the limited set of EBV latency antigens expressed in these
      malignancies, making T-cell expansion difficult. Retroviral transduction of LMP
      specific T-cell receptors (TCR) into activated T lymphocytes may provide a
      universal, MHC-restricted, means to generate effector cells without the need for
      tissue culture based methods of CTL expansion. We report the transfer of two LMP2
      specific TCRs from human T-cell clones (HLA-A2 and HLA-A23,24 restricted) that
      confer the ability to lyse EBV-immortalized B-lymphoblastoid cell lines (B-LCL).
      B-LCL are the best model for native expression of LMP2. We also demonstrate the
      rapid transfer of the TCR by nucleofection of primary T cells using a simple
      plasmid-based vector. The ability to detect nucleofected TCRVbeta chain by
      antibody, fully assembled TCR by tetramer, and peptide-MHC-specific lytic
      activity indicates that nucleofection can serve as a tool for rapid screening of
      TCR specificity.

PMID- 16418801
TI  - Immunopathogenesis of dilated cardiomyopathy. Evidence for the role of TH2-type
      CD4+T lymphocytes and association with myocardial HLA-DR expression.
AB  - BACKGROUND: An immunological pathogenesis underlying dilated cardiomyopathy and
      myocarditis has been suggested on the basis of the subtype of lymphocyte
      infiltrates and the degree of HLA expression in cardiac tissue. In the present
      study, we investigated the relation between the peripheral CD4+T-cell subset and
      the degree of HLA expression in the heart. METHODS: Fifty-four patients with
      heart insufficiency included in the study were biopsied after coronary heart
      disease had been excluded. Immunohistological staining of the left ventricular
      tissue were performed employing anti-CD3, -CD4, -CD8, -CD14, and HLA-DR
      monoclonal antibodies. Intracellular expression of IL-2, IL-4, IL-5, IFN-gamma,
      and TNF-alpha in peripheral CD4+T lymphocytes was determined using flow
      cytometry. The severity of heart insufficiency was determined by measurement of
      brain natriuretic peptide (BNP) and the NYHA class. On the basis of HLA
      expression in the heart, the patients were divided into three groups: Group I
      (mild-to-none), Group II (moderate), and Group III (strong-to-very strong).
      RESULTS: Of the 54 patients included in this study, 33 (61%) patients were
      diagnosed as having idiopathic dilated cardiomyopathy and 10 (18.5%) borderline
      or healing myocarditis according to the Dallas criteria. Both patient groups were
      found in all three HLA-DR groups. There was no difference in BNP level or NYHA
      class between the three groups. However, a significant difference in the
      proportion of CD4+T lymphocytes producing IL-2 (39.2 versus 21.8%), IFN-gamma
      (19.5 versus 7.8%), and TNF-alpha (35.8 versus 16.1%) between Groups I and III
      could be detected, whereas the distribution of IL-4 and IL-5 producing CD4+T
      lymphocytes was similar. The myocardium of Group III patients exhibited a
      significant higher number of CD3+T cells (11.4 versus 4.3 per mm2) and CD4+T
      cells (4.7 versus 0.8 per mm2) compared to Group I patients, while no difference
      existed with respect to CD8+T cells. CONCLUSION: High myocardial expression of
      the HLA-DR antigen is associated with an increase of peripheral-blood CD4+T
      lymphocytes expressing cytokines of the TH2 subset. The degree of HLA-DR
      expression is not associated with the degree of heart insufficiency or underlying
      diagnosis, but correlates with an increase of activated T cells in the
      myocardium. The data suggest that CD4+T lymphocytes infiltrating cardiac tissue
      may play a pathogenic role in dilated cardiomyopathy.

PMID- 16418803
TI  - Variations in plasmacytoid dendritic cell (PDC) and myeloid dendritic cell (MDC)
      levels in HIV-infected subjects on and off antiretroviral therapy.
AB  - Plasmacytoid and myeloid dendritic cells are reduced in AIDS patients. The number
      of these circulating cells was assessed cross-sectionally and longitudinally in
      27 uninfected and 72 HIV-infected subjects on and off antiretroviral therapy. The
      plasmacytoid dendritic cell numbers were significantly reduced in the HIV
      infected subjects compared to controls (p < 0.001). This reduction correlated
      directly with CD4+ cell counts (p < 0.001) and inversely with viral load (p <
      0.001). These associations were found to a lesser degree for the myeloid
      dendritic cells. Intra-assay variability of these dendritic cell counts was <
      10%. Antiretroviral therapy significantly increased plasmacytoid dendritic cell
      (p < 0.001) and CD4+ cell (p = 0.05) counts at 8 months by 76.9% and 19%,
      respectively. The plasmacytoid dendritic cell levels responded more readily to
      viral load increases and decreases than CD4+ cells. Circulating plasmacytoid
      dendritic cells may provide important additional information about immune
      function in HIV-infected subjects receiving or not receiving antiretroviral
      therapy.

PMID- 16418802
TI  - HIV-1-specific CD4+ T cell responses in chronically HIV-1 infected blippers on
      antiretroviral therapy in relation to viral replication following treatment
      interruption.
AB  - The impact of transient viral load blips on anti-HIV-1 immune responses and on
      HIV-1 rebound following treatment interruption (TI) is not known. Clinical and
      immunological parameters were measured during 40 weeks of antiretroviral therapy
      (ART) and following TI in an observational cohort of 16 chronically HIV-1
      infected subjects with or without observed viral load blips during ART. During
      therapy, blips in seven subjects were associated with higher anti-HIV-1 (p24)
      CD4+ T cell lymphoproliferative responses (p = 0.04), without a significant
      difference in T cell activation or total anti-HIV-1 CD8+ T cell interferon-gamma
      (IFN-gamma) responses when compared to nine matched non-blippers. Therapy
      interruption resulted in a significantly higher viral rebound in blippers by 8
      week despite retention of higher lymphoproliferative p24 responses (p = 0.01) and
      a rise in CD3+ T cell activation (p = 0.04) and anti-HIV-1 CD8+ T cell responses
      in blippers by week 4 when compared to non-blippers. Past week 4 of interruption,
      therapy re-initiation criteria were also met by a higher frequency in blippers by
      week 14 (p < 0.04) with no difference between groups by week 24. These data
      support that blippers have higher anti-HIV lymphoproliferative responses while on
      ART but experience equal to higher viral rebound as compared to matched non
      blippers upon TI.

PMID- 16418804
TI  - Health-related quality of life and treatment satisfaction in North American
      patients with primary immunedeficiency diseases receiving subcutaneous IgG self
      infusions at home.
AB  - The lifelong IgG replacement therapy for patients with primary immunedeficiencies
      (PIDD) may be provided by intravenous (IVIG) or by subcutaneous IgG (SCIG)
      infusions. We investigated the impact of weekly SCIG self-infusions at home on
      the health-related quality of life, treatment satisfaction, and preferences in
      patients treated with IVIG at the hospital/doctor's office (Group A) or at home
      (Group B) before the study started. Forty-four adult North American PIDD patients
      were included in the study, 28 patients in Group A and 16 in Group B. Patients in
      Group A reported significantly less limitations with their work/daily activities,
      a significantly improved vitality, and better general health. Treatment
      satisfaction was significantly improved in Group A. The preference for the
      subcutaneous route and for home therapy was respectively 81% and 90% in Group A.
      In Group B, 69% preferred the subcutaneous route and 92% home therapy.

PMID- 16418805
TI  - COX-2 inhibitors modulate IL-12 signaling through JAK-STAT pathway leading to Th1
      response in experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune
      disease model of multiple sclerosis (MS). IL-12 plays a crucial role in the
      pathogenesis of EAE/MS and inhibition of IL-12 production or IL-12 signaling was
      effective in preventing EAE. Cyclooxygenase (COX-2) is a key enzyme promoting
      inflammation in rheumatoid arthritis and tumor induced angiogenesis. Recent
      studies have shown that COX-2 inhibitors prevent EAE, however, their mechanism of
      action is not fully understood. In this study, we show that in vivo treatment
      (i.p.) with 100 mug COX-2 selective inhibitors (LM01, LM08, LM11, and NS398), on
      every other day from day 0 to 30, significantly reduced the incidence and
      severity of EAE in SJL/J and C57BL/6 mice. Further analyses showed that the COX-2
      inhibitors reduced neural antigen-induced IL-12 production, T cell proliferation
      and Th1 differentiation ex vivo and in vitro. The COX-2 inhibitors also decreased
      IL-12-induced T cell responses through blocking tyrosine phosphorylation of JAK2,
      TYK2, STAT3, and STAT4 proteins in T cells. These results demonstrate that COX-2
      inhibitors ameliorate EAE in association with the modulation of IL-12 signaling
      through JAK-STAT pathway leading to Th1 differentiation and suggest their use in
      the treatment of MS and other Th1 cell-mediated autoimmune diseases.

PMID- 16418806
TI  - Induction of pathogenic anti-dsDNA antibodies is controlled on the level of B
      cells in a non-lupus prone mouse strain.
AB  - The SmD1(83-119) peptide is a main target of autoantibodies and T cells in human
      and murine lupus, but its role in autoimmunity induction remains elusive.
      Therefore, female Balb/c mice and (NZW x Balb/c)F1 [CWF1] mice with identical MHC
      haplotype as lupus prone NZB/W mice were immunized with SmD1(83-119).
      Immunizations of CWF1 mice with SmD1(83-119), but not with the controls
      (irrelevant peptide, HEL peptide, or saline), induced anti-SmD1(83-119) and anti
      dsDNA antibodies and proteinuria not present in Balb/c mice. DsDNA-specific
      plasma cell induction after SmD1(83-119) immunizations was confirmed by ELISPOT
      assays showing that the generation of dsDNA-specific antibody forming cells (AFC)
      was mainly driven by increased T-cell help. T-cell help for the generation of
      dsDNA-specific AFC was also present in saline-treated CWF1 mice but was
      controlled on the levels of B cells preventing autoimmunity.

PMID- 16418807
TI  - Thymic function-related markers within the thymus and peripheral blood: Are they
      comparable?
AB  - The thymus involutes with age and its functionality has traditionally been
      assumed to be limited early in life. However, some studies have demonstrated that
      thymic function persists in adults. In humans, since it is difficult to obtain
      thymic samples from healthy individuals, indirect parameters have been used to
      study the thymic function. The aim of this study was to compare thymic function
      parameters within both the thymus and peripheral blood mononuclear cells from
      thirty-three patients who underwent cardiac surgery, as well as to relate these
      parameters with aging. The proportion of peripheral naive T cells and intrathymic
      T cell differentiation stages, as well as peripheral and intrathymic TREC levels
      were analysed. We demonstrated that thymopoyesis persists in the healthy elderly
      since all T cell differentiation stages were found within the thymus. Among the
      studied parameters, peripheral TREC levels are found to be a good thymic function
      marker since they correlated with age. In healthy individuals, peripheral TREC
      levels are a good reflect of thymic function as demonstrated by their correlation
      with intrathymic TREC values.

PMID- 16418808
TI  - [Cardiac structure and function in patients with obstructive sleep apnea syndrome
      and co-prevalent arterial hypertension. Influence of CPAP therapy].
AB  - BACKGROUND AND PURPOSE: 30% of patients with arterial hypertension (AH) are
      supposed to have a co-prevalent obstructive sleep apnea syndrome (OSAS). Hence,
      the influence of CPAP (continuous positive airway pressure) therapy on cardiac
      structure and function was investigated in medically treated patients with AH and
      co-prevalent OSAS. PATIENTS AND METHODS: In all patients AH was treated for at
      least 5 years. Matched pairs concerning anthropometric data, medical therapy and
      duration of AH, and severity of OSAS were investigated: 20 patients with
      untreated OSAS were compared to 20 patients with CPAP therapy for at least 6
      months. Further cardiopulmonary diseases were excluded. Cardiac structure and
      function were assessed echocardiographically. RESULTS: Patients under CPAP
      therapy had significantly better diastolic left ventricular function, a lower
      left ventricular mass index, and significantly less frequent signs of left
      ventricular (eccentric) hypertrophy than patients with untreated OSAS.
      Furthermore, differences were significant concerning right ventricular wall
      thickness and mean pulmonary artery pressure. CONCLUSION: CPAP therapy positively
      influences left and right cardial structure and function in addition to
      antihypertensive medication in patients with AH and co-prevalent OSAS.

PMID- 16418809
TI  - [Why does evidence-based medicine need the international classification of
      functioning, disability, and health?].
AB  - OBJECTIVE: Evidence-based medicine (EBM) aims at finding the currently best
      answer to the questions raised by a patient's disease through rationally
      comparing different diagnostic and therapeutic alternatives. THESIS: As a
      rational method, EBM also needs a rational reference system. ICF, the
      International Classification of Functioning, Disability, and Health, officially
      translated into German in 2004, is such a reference system. DISCUSSION OF THE
      POSSIBLE ROLE OF THE ICF IN EBM: ICF, a supplementary classification to ICD,
      consists of the four components: body functions and body structures, activities
      and participation, environmental factors, and personal factors (not yet
      classified). ICF describes the interdependence between all the factors
      influencing health as well as disease. For EBM, ICF can serve as a reference
      system: when defining a therapy's goal and examining whether it was reached, for
      including and excluding criteria of target groups, checking whether control and
      intervention groups are comparable, finding out relevant prognostic factors,
      defining the requirement of an intervention, applying assessments, or grouping
      people with similar need of help for payment.

PMID- 16418811
TI  - [Limb apraxia].
AB  - Apraxia is the disturbance of planning and of execution of motor activity. It is
      not caused by a lesion or a disturbance of the motor or sensory nervous system,
      it is elicited by a dysfunction of an area in the left cortex of the brain. This
      area in the left fronto-parietotemporal hemisphere is located right beside the
      area for speech. Therefore it is not unusual that patients with apraxia suffer
      from aphasia as well. The two different types of limb apraxia are ideomotor
      apraxia and ideational apraxia. Ideomotor apraxia is apraxia without tool use, it
      includes imitation of positions of hands and fingers, performance of gestures on
      demand, and pantomime of object use. Ideational apraxia is apraxia with tool use
      like cutting with a knife or utilizing a pencil.

PMID- 16418810
TI  - [Therapeutic management of acromegaly].
AB  - BACKGROUND: Only 60% of the patients with acromegaly are biochemically cured
      (growth hormone [GH] nadir < 1.0 microg/l after an oral glucose load, normalized
      age- and gender-matched insulin-like growth factor-1 [IGF-1] levels) after
      transsphenoidal surgery of the pituitary gland. In the absence of a remission
      there are effective pharmacological treatment regimens available which are able
      to lower GH and IGF-1 serum levels. THERAPEUTIC STRATEGIES: Somatostatin analogs,
      a GH receptor antagonist and dopamine agonists have been shown to alleviate the
      comorbid features and to normalize GH and IGF-1 levels. CASE REPORTS: In this
      overview six case reports are presented to highlight the current pharmacological
      treatment options and to propose an algorithm for the clinical routine in
      patients with persisting acromegaly. CONCLUSION: Transsphenoidal surgery is the
      treatment of choice for the initial management of acromegaly. In the absence of a
      remission there are effective pharmacological treatment regimens available among
      which somatostatin analogs are recommended as the first-line treatment.

PMID- 16418813
TI  - ["Medical Emergency Services as Seen by Consumers". Health services research by
      CATI survey of the community].
AB  - BACKGROUND: In the Wesel district (North Rhine-Westphalia), emergency ambulances
      have been called out with increasing frequency and hospitals report that their
      emergency departments (ED) are more and more being used outside consultation
      hours of panel doctors. Therefore, the district health conference put this issue
      on its agenda. PURPOSE: The aim was to obtain data on the following questions: *
      What do people do when they need medical help outside consultation hours of panel
      doctors? * Do people know that there is an on-call duty by panel doctors? Do they
      know how to contact this service? Do people know the Emergency Medical Service
      and phone number 112 and the new phone number 19222 for Patient Transport
      Ambulances? MATERIAL AND METHODS: The study population was defined as comprising
      all residents in the district of Wesel between 18 and 87 years of age
      (approximately 385,000 people). The sample contained 1,089 persons drawn in
      accordance with the Gabler-Hader method and in a second step the "birthday
      method" was used. The survey was carried out by the CATI Laboratory (Computer
      Assisted Telephone Interviews) at the Institute of Public Health (logd,
      Bielefeld, Germany) between February 18 and March 28, 2002. RESULTS: (1) Being
      asked: "How would you act in case of a non-life-threatening disease outside
      consultation hours of panel doctors?", 52.6% of the respondents gave at least one
      correct answer; 48.6 % of all given answers were "correct" (i. e., on-call duty
      of Statutory Health Insurance [SHI]-accredited physicians), the others were
      "incorrect", i. e., "I go to the hospital/emergency department" (24.3%) or "I
      call the phone number 112" (13%). (2) About 80% of respondents said they heard
      about the on-call duty of SHI physicians. (3) 95.6% of respondents stated they
      knew the emergency call of the fire department; 86% of these participants were
      able to name the correct phone number 112. (4) About 4% of the respondents said
      they knew the nationwide telephone number for patient transports, and 58% of
      these respondents mentioned the correct number 19222. CONCLUSION: A) The tiered
      medical emergency system should be used adequately; this aim could be attained by
      (1) information of the public about the "24-h" on-call service of panel doctors;
      information about the fact that the majority of medical conditions can be treated
      by panel doctors and that in severe cases a professional and quick referral will
      be done; information about the fact that self-referral to hospitals may reduce or
      even obstruct professional resources for the treatment of "real" emergency
      patients. Target groups are men, younger age groups and people with a higher
      level of education. (2) information of target groups (elderly people) about the
      emergency call number 112. (3) information of the public about the national phone
      number 19222 for patient transports. B) Structural measures such as (1) specific
      on-call services, (2) improvement of the transparency and reach-ability of panel
      doctors' on-call services.

PMID- 16418812
TI  - [The latest developments in endocrinology 2004/2005].
AB  - The following review presents recent diagnostic and therapeutic developments in
      the field of endocrinology. With the development of strontium ranelate and
      teriparatide (human recombinant parathyroid hormone) two new drugs are now
      available for the treatment of postmenopausal osteoporosis. In addition, the
      therapeutic use of the calcimimetic agent cinacalcet in the treatment of primary
      and secondary hyperparathyroidism is discussed. The recent introduction of a
      novel, long-acting testosterone formulation (testosterone undecanoate) which only
      requires one intramuscular injection every 3 months, together with the already
      available hydroalcoholic testosterone gels, appear to be promising alternatives
      to the previous standard substitution therapy for male hypogonadism. Recently,
      the mineralocorticoid hormone aldosterone has gained much interest due to its
      central pathophysiological role in secondary hypertension and its potential
      deleterious role as a cardiovascular risk factor in nonepithelial target tissues.
      In this context, the therapeutic potential of a new selective mineralocorticoid
      receptor antagonist, eplerenone, will be ventilated. In addition, (18)F-DOPA
      positron emission tomography ((18)F-DOPA-PET), a new functional imaging modality
      for the diagnostic localization of chromaffin tumors, will be presented and the
      role of the somatostatin receptor radionuclide therapy with (90)Y-[DOTA](0)
      Tyr(3)-octreotide ((90)Y-DOTATOC) for the treatment of advanced neuroendocrine
      tumors discussed. Furthermore, the ongoing controversy about the diagnosis and
      treatment of subclinical hypothyroidism will be summarized.

PMID- 16418814
TI  - [Diverticulosis/diverticulitis? What are conservative therapy possibilities?].

PMID- 16418816
TI  - [Endosonography -- an additional diagnostic possibility in the differentiation
      between the two common types of primary hyperaldosteronism].
AB  - BACKGROUND: Primary aldosteronism is an important and one of the few potentially
      curable forms of secondary hypertension. The distinction between aldosterone
      producing adenoma (APA) and idiopathic adrenal hyperplasia (IHA) may be
      difficult, but establishing the correct diagnosis is essential because surgery is
      only effective in patients with adrenal adenoma. CASE REPORT: The case of a 65
      year-old man with long-term hypertension due to an APA is reported. The routine
      laboratory tests displayed an elevated plasma aldosterone/renin quotient as well
      as an elevated 24-h urinary excretion of aldosterone and its metabolites. The
      serum aldosterone concentration did not decrease normally in the saline
      suppression test. The posture testing demonstrated an increase in aldosterone.
      These facts might lead to the conclusion of an IHA. Magnetic resonance imaging
      (MRI) of the adrenal glands revealed no abnormalities. Because of the unusual
      combination of laboratory findings and radiologic results an endosonographic
      examination of the adrenal glands was performed which yielded a unilateral
      adrenal adenoma. With establishing this diagnosis, curative surgery became
      possible. CONCLUSION: This case demonstrates that in the differential diagnosis
      of primary aldosteronism, endosonography is more important than previously
      discussed. It may be helpful in the differentiation of an unusual constellation
      of laboratory and radiologic findings.

PMID- 16418815
TI  - [Guidelines for diagnosis and therapy of patients with asthma 2005. The most
      important aspects for adults].

PMID- 16418817
TI  - [Gastrointestinal stromal tumors (GIST). Clinical characteristics, diagnosis, and
      therapy in five cases].
AB  - Gastrointestinal stromal tumors (GIST) are rare causes of gastrointestinal
      bleeding. In most cases these tumors are localized in the stomach and small
      intestine, more rarely in the esophagus and colon.Pluripotent mesenchymal cells
      are the suspected origin of GIST. The pathogenesis is obviously initiated by gene
      mutations, leading to an overexpression and activation of tyrosine kinase
      proteins. This activation is followed by uncontrolled proliferation and loss of
      apoptosis. The immunohistochemical detection of the protein CD 117 (c-kit) is an
      important diagnostic tool. Activating c-kit mutations are observed in most cases
      of GIST. Grading of GIST remains a problem. Size and mitotic rate are the most
      powerful predictive factors associated with malignant behavior. The most common
      symptoms of GIST are pain and gastrointestinal bleeding. Endoscopy, sonography,
      scintigraphy or radiology -- enteroclysma, computed tomography (CT) and magnetic
      resonance imaging (MRI) -- are possible methods to detect a GIST. Surgical
      resection is the standard therapy of GIST. In cases of metastatic GIST, systemic
      therapy with imatinib, a tyrosine kinase inhibitor, frequently leads to partial
      remission and clinical improvement. Only few side effects are described. Five
      patients with GIST are reported. In all cases gastrointestinal bleeding was the
      main symptom. All tumors were surgically resected, and no signs of recurrence or
      metastasis have been observed in any of the patients so far (19-51 months
      postoperatively).

PMID- 16418818
TI  - [DRG and coding. Sleep apnea and noninvasive respiration].

PMID- 16418819
TI  - [Stem cell therapy in chronic heart failure].
AB  - BACKGROUND: An increasing number of patients survives acute myocardial infarction
      and reaches the stage of chronic heart failure-but today therapeutic
      possibilities in end stage of heart failure are limited because of a lack of
      donor organs. RESULTS: Stem cell therapy is a promising new therapeutic strategy.
      In first clinical studies feasibility and efficacy of catheter-based application
      or cytokine-induced mobilisation of autologous stem cells have been examined in
      acute myocardial infarction and in chronic heart failure. While efficacy of
      autologous stem cells is uncertain and potential of regeneration might be to low,
      embryonic stem cells could represent another important option in future: because
      of pluripotency and a high potential of proliferation embryonic stem cells are
      the optimal resource for tissue engineering. Heart tissue which was generated in
      vitro could be transplanted in patients with chronic heart failure to increase
      cardiac function. CONCLUSION: Whereas adult stem cells are applied in first
      clinical studies in myocardial infarction, embryonic stem cells are not
      clinically used yet. Nevertheless, embryonic stem cells might play an important
      role in therapy of chronic heart failure in future.

PMID- 16418820
TI  - [50 years to Saarland-Pfalz internist society. Retrospect of the development of
      internal medicine in the Saar-Pfalz-Mosel region since 1956].

PMID- 16418821
TI  - [Methods in health services research. The example of the evaluation of the German
      disease management programmes].
AB  - According to the established definition of Pfaff, health services research
      analyses patients' path through the institutions of the health care system. The
      focus is on development, evaluation and implementation of innovative measures of
      health care. By increasing its quality health services research strives for an
      improvement of efficacy and efficiency of the health care system. In order to
      allow for an appropriate evaluation it is essential to differentiate between
      structure, process and outcome quality referring to (1) the health care system in
      its entirety, (2) specific health care units as well as (3) processes of
      communication in different settings. Health services research comprises a large
      array of scientific disciplines like public health, medicine, social sciences and
      social care. For the purpose of managing its tasks adequately a special
      combination of instruments and methodological procedures is needed. Thus, diverse
      techniques of evaluation research as well as special requirements for study
      designs and assessment procedures are of vital importance. The example of the
      German disease management programmes illustrates the methodical requirements for
      a scientific evaluation.

PMID- 16418823
TI  - [Quality assurance in transfusion and blood coagulation therapy according to the
      current guidelines of the German Medical Association].

PMID- 16418825
TI  - Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic
      evidence, therapeutic implications.
AB  - RATIONALE: Oxytocin (OT) acts as a neuromodulator/neurotransmitter within the
      central nervous system (CNS) and regulates a diverse range of CNS functions.
      Notably, evidence from studies in females has revealed an important role for OT
      in regulating anxiety behavior. OBJECTIVES: The objective of this study was to
      examine the effects of OT on both behavioral and autonomic parameters of the
      anxiety response in male mice using three pharmacologically validated preclinical
      models of anxiety: the four-plate test (FPT), elevated zero maze (EZM), and
      stress-induced hyperthermia (SIH). RESULTS: In the FPT, both peripherally (3-30
      mg/kg i.p.) and centrally (1-10 microg i.c.v.) administered OT produced dose
      dependent increases in punished crossings, indicating an anxiolytic-like effect.
      The effects of centrally administered OT in the FPT were blocked with peripheral
      administration of a brain-penetrant OT receptor (OTR) antagonist WAY-162720 (30
      mg/kg i.p.), and the effects of peripherally administered OT were blocked with
      central administration of a non-penetrant OTR antagonist L-371,257, suggesting OT
      acts centrally. In the EZM, centrally administered OT (0.1-1.0 microg, i.c.v.)
      produced significant increases in the percentage time spent in the open quadrants
      of the maze, comparable to alprazolam (0.5-1.0 microg, i.c.v.). In SIH, OT (1-10
      mg/kg i.p.) dose-dependently attenuated stress-induced increases in core body
      temperature, comparable to the reference anxiolytic chlordiazepoxide (CDP) (10
      mg/kg i.p.). CONCLUSIONS: These results provide specific behavioral and autonomic
      evidence of anxiolytic-like effects for oxytocin in males and, together with
      previously reported observations in females, suggest the potential utility of OTR
      agonism as a therapeutically relevant mechanism of action for novel anxiolytics
      in both sexes.

PMID- 16418824
TI  - Effects of G-CSF on left ventricular remodeling and heart failure after acute
      myocardial infarction.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that
      promotes proliferation and differentiation of neutrophil progenitors. G-CSF also
      possesses immunomodulatory properties. G-CSF-induced hematopoietic stem cell
      mobilization is widely used clinically for transplantation. After it was recently
      reported that G-CSF mobilizes bone marrow stem cells (BMSCs) into the infarcted
      hearts and accelerates the differentiation into vascular cells and cardiac
      myocytes, myocardial regeneration utilizing mobilization of BMSCs by G-CSF is
      attracting the attention of investigators. In animal models, G-CSF prevents left
      ventricular remodeling and dysfunction after acute myocardial infarction, at
      least in part, through a decrease in apoptotic cells and an increase in vascular
      cells. Although it is controversial whether BMSCs mobilized by G-CSF can
      differentiate into cardiac myocytes, G-CSF-induced angiogenesis is indeed
      recognized in infarcted heart. The cardioprotective effects of G-CSF are
      recognized even in isolated perfused heart. In addition, G-CSF activates various
      signaling pathways such as Akt, extracellular signal-regulated kinase, and Janus
      kinase 2/signal transducer and activator of transcription 3 through G-CSF
      receptors in cardiac myocytes. These observations suggest that G-CSF not only
      induces mobilization of stem cells and progenitor cells but also acts directly on
      cardiomyocytes. Therefore, G-CSF may be utilized as a novel agent to have
      protective and regenerative effects on injured myocardium. Although the effects
      of G-CSF on the progression of atherosclerosis are still unclear, there is a
      possibility that G-CSF will become a promising therapy for ischemic heart
      diseases.

PMID- 16418826
TI  - Different patterns of pharmacological reinstatement of cocaine-seeking behavior
      between Fischer 344 and Lewis rats.
AB  - RATIONALE: Fischer 344 (F344) and Lewis (LEW) rats differ in cocaine self
      administration behaviors. Whether or not these inbred strains of rats differ in
      pharmacological reinstatement of cocaine-seeking behavior is unknown. OBJECTIVES:
      The purpose of the present study was to determine if inbred strains of rats
      demonstrate differences in alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic
      acid (AMPA) and cocaine-induced reinstatement of previously extinguished cocaine
      seeking behavior. METHODS: F344 and LEW rats received indwelling jugular
      catheters, bilateral guide cannula aimed at the nucleus accumbens core, and were
      trained to lever press for 0.5 mg/kg intravenous cocaine during 2-h self
      administration sessions. Following 14 sessions, rats underwent extinction
      sessions, where previously reinforced lever pressing resulted in no programmed
      consequences. Just prior to beginning extinction session 7, rats received an
      intracranial infusion of saline. Lever pressing was not reinforced. During
      subsequent extinction sessions, rats received AMPA injections (0.2, 0.4, or 0.6
      nM). Dosing order was determined by a within-subject Latin square design. At
      least two extinction sessions separated each AMPA session. Rats then underwent
      cocaine-induced reinstatement test sessions (lever pressing was not reinforced).
      Rats received passive intravenous cocaine (0.0, 0.5, 1.0, or 2.0 mg/kg) after
      being placed in the experimental chamber. At least two extinction sessions
      separated each cocaine-prime session, and subjects were tested at each dose
      according to a within-subjects Latin square design. RESULTS: LEW rats
      demonstrated blunted maximal responding to AMPA-induced reinstatement and
      heightened sensitivity to cocaine-induced reinstatement compared with F344 rats.
      CONCLUSIONS: This study demonstrates that inbred strains differ in
      pharmacological reinstatement of cocaine-seeking behavior.

PMID- 16418827
TI  - Relationship of disinhibition and aggression to blunted prolactin response to
      meta-chlorophenylpiperazine in cocaine-dependent patients.
AB  - RATIONALE: Considerable evidence indicates that serotonergic (5-HT) mechanisms
      may mediate central effects of cocaine, and disinhibition and aggression.
      OBJECTIVE: We investigated whether prolactin (PRL) response to meta
      chlorophenylpiperazine (m-CPP), a mixed 5-HT agonist/antagonist, differed between
      abstinent cocaine-dependent patients and controls and whether m-CPP challenge
      responses were related to measures of disinhibition and aggression. METHODS:
      Thirty-five cocaine-dependent African-American subjects who were abstinent for at
      least 2 weeks and 33 African-American controls underwent assessments of
      disinhibition and aggression and a challenge with 0.5 mg/kg of oral m-CPP.
      RESULTS: The PRL response to m-CPP was compared between cocaine patients and
      controls and between subgroups categorized high or low based on disinhibition and
      aggression measures. Hierarchical regressions were used to determine whether
      behavioral measures predicted deltaPRL (peak PRL-baseline PRL). The PRL response
      to m-CPP was significantly diminished in cocaine patients compared to controls.
      The blunting was more robust in cocaine patients with high disinhibition and
      aggression. Among cocaine patients, the high-disinhibition subgroup showed
      greater blunting than the low-disinhibition subgroup and there was a trend for
      the high-aggression subgroup to be more blunted than the low-aggression subgroup.
      The subgroups of controls did not differ from each other. A combination of
      disinhibition and aggression measures significantly predicted deltaPRL in cocaine
      patients. CONCLUSION: The results indicate that cocaine-dependent patients show
      disturbances in postsynaptic 5-HT function during early abstinence. It appears
      that the 5-HT disturbances are more pronounced in the subgroup of cocaine
      patients with high disinhibition and aggression.

PMID- 16418830
TI  - Isolation of Brucella melitensis from a patient with hearing loss.

PMID- 16418831
TI  - First case of febrile bacteremia due to a wild type and small-colony variant of
      Escherichia coli.
AB  - Reported here is a case of a febrile illness caused by a wild type and small
      colony variant of Escherichia coli in an anorectic patient. A review of the
      literature revealed that the formation of small-colony variants in E. coli has
      been recognized since 1931. In recent years, an association has been established
      between those variants and chronic recurrent infections. This report describes
      for the first time the isolation of an E. coli small-colony variant from a blood
      culture of a patient who had suffered from chronic urinary tract infections in
      the past.

PMID- 16418828
TI  - Teaching communication and stress management skills to junior physicians dealing
      with cancer patients: a Belgian Interuniversity Curriculum.
AB  - BACKGROUND: Ineffective physicians' communication skills have detrimental
      consequences for patients and their relatives, such as insufficient detection of
      psychological disturbances, dissatisfaction with care, poor compliance, and
      increased risks of litigation for malpractice. These ineffective communication
      skills also contribute to everyday stress, lack of job satisfaction, and burnout
      among physicians. Literature shows that communication skills training programs
      may significantly improve physicians' key communication skills, contributing to
      improvements in patients' satisfaction with care and physicians' professional
      satisfaction. This paper describes a Belgian Interuniversity Curriculum (BIC)
      theoretical roots, principles, and techniques developed for junior physicians
      specializing in various disciplines dealing with cancer patients. CURRICULUM
      DESCRIPTION: The 40-h training focuses on two domains: stress management skills
      and communication skills with cancer patients and their relatives. The teaching
      method is learner-centered and includes a cognitive, behavioral, and affective
      approach. The cognitive approach aims to improve physicians' knowledge and skills
      on the two domains cited. The behavioral approach offers learners the opportunity
      to practice these appropriate skills through practical exercises and role plays.
      The affective approach allows participants to express attitudes and feelings that
      communicating about difficult issues evoke. Such an intensive course seems to be
      necessary to facilitate the transfer of learned skills in clinical practice.
      CONCLUSIONS: The BIC is the first attempt to bring together a stress management
      training course and a communication training course that could lead not only to
      communication skills improvements but also to burnout prevention.

PMID- 16418832
TI  - Disseminated strongyloidiasis: a retrospective study of clinical course and
      outcome.
AB  - A retrospective study was carried out to evaluate the clinical course and outcome
      of disseminated strongyloidiasis treated in a regional hospital in Hong Kong over
      a 10-year period. Seven cases were identified, and the case history of each
      patient was analysed. The most common presenting symptom was fever (100%). Five
      (71%) patients had gastrointestinal symptoms, the most common being abdominal
      pain and diarrhoea. Three (42%) patients had a significant drop in haemoglobin.
      Six (85%) patients had bronchoalveolar infiltrates on chest radiographs. Most
      patients were immunosuppressed by means of steroid treatment for their underlying
      primary disease. One patient was diabetic, and another had lymphoma and was
      receiving chemotherapy. Strongyloides larvae were identified in stool specimens
      in two patients, in sputum smears in two patients, and in gastric biopsies in
      three patients. Five (71%) of the patients with lung involvement progressed to
      respiratory failure and died. Two (29%) cases were complicated by gram-negative
      bacterial infection. No patient had eosinophilia on presentation. All patients
      received antihelminthic treatment of variable duration. The case fatality rate in
      the cohort was 71% despite aggressive supportive therapy. Pulmonary and bowel
      symptoms were prominent in our series. In conclusion, the diagnosis of
      disseminated strongyloidiasis is often delayed because of nonspecific presenting
      symptoms. Early diagnosis relies on a high index of clinical suspicion,
      especially in immunocompromised hosts. Screening for Strongyloides infection
      before the initiation of immunosuppressive therapy should be considered,
      especially in endemic areas.

PMID- 16418834
TI  - Chiari I malformation and idiopathic growth hormone deficiency in siblings.
AB  - INTRODUCTION: The authors report a case of three brothers. Two of these siblings
      presented with congenital growth hormone deficiency and Chiari I malformation.
      The third and younger brother has been found not to have growth hormone
      deficiency or the Chiari I malformation. RESULTS: Sparse cases of these two
      clinical occurrences have been reported. Further, the posterior cranial fossa has
      been determined to be altered in patients with Chiari I malformation and growth
      hormone deficiency. CONCLUSION: Our current case reports strengthen the
      association between these two pathological entities and are, to our knowledge,
      the first description of both defects in siblings.

PMID- 16418835
TI  - Systematic assessment of constipation on plain abdominal radiographs in children.
AB  - BACKGROUND: Constipation in childhood is common and its clinical assessment is
      often difficult. Plain abdominal radiography is simple and used to quantify
      constipation. Three scoring systems, those of Barr et al., Leech et al. and
      Blethyn et al., have been developed to quantify fecal loading on the abdominal
      radiograph. OBJECTIVE: In order to determine which method is the most useful in
      clinical practice, we assessed the reproducibility of the three scoring systems.
      MATERIALS AND METHODS: Plain abdominal radiographs from 40 clinically constipated
      children were retrospectively reviewed by two paediatric radiologists on two
      separate occasions. The radiographs were scored according to three different
      systems developed by Barr et al., Leech et al., Blethyn et al. Intraobserver
      variability and interobserver reproducibility were determined for each system.
      Kappa coefficients were calculated as indicators of inter- and intraobserver
      agreement for categorical outcome variables. RESULTS: The Leech score showed the
      highest reproducibility: the intraobserver agreement was high for both observers
      (kappa values of 0.88 and 1.00, respectively, P<0.05). Furthermore, the
      interobserver agreement was also high: kappa 0.91 in the first round and 0.84 in
      the second. CONCLUSIONS: The Leech score proved to be a highly reproducible tool
      for assessment of childhood constipation and is of value in clinical practice for
      systematic assessment of constipation on plain abdominal radiographs in children.

PMID- 16418836
TI  - Spatial and temporal expression profiles suggest the involvement of gelatinase A
      and membrane type 1 matrix metalloproteinase in amphibian metamorphosis.
AB  - The matrix metalloproteinases (MMPs) are a family of proteases capable of
      degrading various components of the extracellular matrix (ECM). Among them, the
      membrane type MMP-1 (MT1-MMP) has been shown to participate in the activation of
      MMP gelatinase A (GelA), suggesting that they may function together in
      development and pathogenesis. Here, we have investigated the spatiotemporal
      expression profiles of Xenopus laevis MT1-MMP and GelA genes during thyroid
      hormone-dependent metamorphosis. We have focused our studies on two organs: (1)
      the intestine, which undergoes first the degeneration of the tadpole epithelium
      through apoptosis and then the development of adult epithelium and other tissues,
      and (2) the tail, which completely resorbs through programmed cell death. We show
      that both MT1-MMP and GelA are upregulated in the intestine and tail when both
      organs undergo metamorphosis. Within the organs, MT1-MMP and GelA are coexpressed
      in the connective tissues during both natural and thyroid-hormone-induced
      metamorphosis. In addition, MT1-MMP (but not GelA) is also expressed in the
      longitudinal muscle cells of the metamorphosing intestine. These results suggest
      that MT1-MMP and GelA function together in the ECM degradation or remodeling
      associated with metamorphosis and that MT1-MMP has additional GelA-independent
      roles in the development of adult longitudinal muscle in the intestine.

PMID- 16418837
TI  - Differential regulation of TIMP-1, -2, and -3 mRNA and protein expressions during
      mouse incisor development.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) possess multiple functions, in
      addition to their matrix metalloproteinase (MMP) inhibitory activity. The
      continuously growing incisor of mouse possesses a stem cell compartment at the
      apical end of the epithelium (the apical loop) and thus provides an excellent
      tool to analyze the mechanisms of organogenesis and cytodifferentiation. To
      understand the functions of TIMPs in tooth development, we have analyzed the gene
      expression and protein localization of TIMP-1, -2, and -3 during mouse incisor
      development, from embryonic day 13 (E13) to postnatal day 3 (P3). TIMP-1 was
      present on the basement membrane during early developmental stages. At P2, TIMP-1
      was strongly detected along the apical loop, transiently disappeared from the
      basement membrane in the cytodifferentiation zone, and later reappeared at the
      distal end of functional ameloblasts. Expression of TIMP-2 protein was restricted
      to the outer part of the apical loop throughout the examined stages. At P2, TIMP
      2 was present on the basement membrane at the outer part of the apical loop. The
      dental follicle also expressed Timp-2, and the corresponding protein was abundant
      within the extracellular matrix. Timp-3 mRNA was highly expressed in the
      mesenchyme surrounding the apical loop. During matrix formation, Timp-3 was
      expressed by subodontoblasts, and the protein was detected in this layer and
      between odontoblasts. Distinct temporal and spatial expression patterns of TIMPs
      suggest divergent functions of these factors in incisor organogenesis.

PMID- 16418838
TI  - Separate neurochemical classes of sympathetic postganglionic neurons project to
      the left ventricle of the rat heart.
AB  - The sympathetic innervation of the rat heart was investigated by retrograde
      neuronal tracing and multiple label immunohistochemistry. Injections of Fast Blue
      made into the left ventricular wall labelled sympathetic neurons that were
      located along the medial border of both the left and right stellate ganglia.
      Cardiac projecting sympathetic postganglionic neurons could be grouped into one
      of four neurochemical populations, characterised by their content of calbindin
      and/or neuropeptide Y (NPY). The subpopulations of neurons contained
      immunoreactivity to both calbindin and NPY, immunoreactivity to calbindin only,
      immunoreactivity to NPY only and no immunoreactivity to calbindin or NPY.
      Sympathetic postganglionic neurons were also labelled in vitro with rhodamine
      dextran applied to the cut end of a cardiac nerve. The same neurochemical
      subpopulations of sympathetic neurons were identified by using this technique but
      in different proportions to those labelled from the left ventricle. Preganglionic
      terminals that were immunoreactive for another calcium-binding protein,
      calretinin, preferentially surrounded retrogradely labelled neurons that were
      immunoreactive for both calbindin and NPY. The separate sympathetic pathways
      projecting to the rat heart may control different cardiac functions.

PMID- 16418839
TI  - Phosphate concentration in artificial tears.
AB  - BACKGROUND: Irrigating solutions and eye drops may contain phosphates as part of
      their buffer system. In the presence of epithelial keratopathy, a high
      concentration of phosphate favours corneal calcification. Knowledge of the
      phosphate concentration in artificial tear products helps to prevent this sight
      threatening complication. This study gives an overview on the amount of phosphate
      contained in artificial tears. METHODS: Fifty-nine samples of commercially
      available artificial tear preparations were tested. The quantification of
      phosphate was performed using the molybdate method on a Modular P autoanalyzer.
      RESULTS: Twenty-six of 59 (44%) artificial tear products had a phosphate
      concentration above physiological levels (>1.45 mmol/l). A phosphate
      concentration above 25 mmol/l was found in nine products (15%), a concentration
      higher than 50 mmol/l in three (5%). CONCLUSIONS: Many artificial tear
      formulations contain unphysiological levels of phosphate, but very high
      concentrations are found only in a few products. These preparations have the
      potential to favour the formation of insoluble crystalline calcium phosphate
      deposits when used on a damaged corneal surface, and should therefore be used
      cautiously.

PMID- 16418840
TI  - In vivo redirection of retinal blood flow into borosilicate micro-cannulas in
      rabbits.
AB  - BACKGROUND: Microvascular manipulation is one application in the emerging field
      of retinal vascular surgery that could lead to new therapeutic approaches for
      retinal disease. Research in this field has largely focused on vessel cannulation
      and injection of vasoactive substances. This study expands on applications for
      retinal vessel manipulation by demonstrating that redirection of retinal blood
      flow in vivo can be achieved through retinal vessel cannulation in a rabbit
      model. METHODS: Dutch-belted rabbits were anesthetized, and a sectoral peritomy
      and sclerotomy 1 mm from the superotemporal limbus were performed. Borosilicate
      glass microtips with external diameters of 10-20 mum were introduced into the
      vitreous through the sclerotomy site. Using an operating microscope and a direct
      contact lens for visualization, we cannulated the rabbits' retinal vessels, and
      blood flow was redirected through the microtips. RESULTS: Retinal vessels
      approximately 30-60 mum in size were cannulated, and controlled blood flow
      through the microcannula was demonstrated with minimal or no vitreous hemorrhage.
      Though still achievable, flow after arterial cannulation was more difficult to
      demonstrate. CONCLUSIONS: This study demonstrates that partial diversion of blood
      flow from a native vessel lumen could be successfully accomplished by retinal
      vessel cannulation. This early work indicates that more advanced retinal vascular
      procedures, such as vessel bypass around a thrombus or shunting blood towards an
      area of ischemic retina, may be feasible in the future.

PMID- 16418841
TI  - Multihormonality and entrapment of islets in pancreatic endocrine tumors.
AB  - We analyzed pancreatic endocrine tumors (PETs) from 200 patients for the
      incidence of multihormonality and entrapped islets and correlated the results
      with clinicopathological features. Our series included 86 cases (43%) of
      functioning PET and 114 cases (57%) of nonfunctioning PET. Classified according
      to the WHO classification, there were 32 well-differentiated benign PETs, 85 well
      differentiated PETs with uncertain behavior, and 83 well-differentiated malignant
      PETs. All tumors were immunostained for pancreatic hormones (insulin, glucagon,
      somatostatin, and pancreatic polypeptide) and for additional hormones such as
      gastrin, vasoactive intestinal polypeptide, calcitonin, seratonin, and
      adrenocorticotropic hormone. Multihormonality was found in 34% of all PETs and it
      was a frequent finding in the tumors of the uncertain behavior (38.8%) group.
      Islet entrapment was found in 57 tumors (28.5%) and was significantly more
      frequent in PETs with uncertain and malignant behavior than benign ones (p=0.01).
      In 57 cases, we also investigated whether ductule entrapment accompanied islet
      entrapment. Of these 57 tumors, 45 (79%) tumors had accompanying ductule
      entrapment. Ductule entrapment did not show significant correlation with
      malignancy and was a more frequent finding in nonfunctioning tumors. We conclude
      that the incidence of multihormonality in PETs is not as high as suggested
      previously and islet entrapping may reflect aggressive tumor growth and may be a
      complementary criterion for predicting the biological behavior of PETs.

PMID- 16418843
TI  - The influence of rTMS over the left dorsolateral prefrontal cortex on Stroop task
      performance.
AB  - Several studies have demonstrated that repetitive transcranial magnetic
      stimulation (rTMS) can improve cognitive processing. Neuroimaging studies have
      shown the engagement of the left dorsolateral prefrontal cortex (DLPFC) in
      executive functioning, and more specifically during selective attention. In the
      present study, the influence of high-frequency rTMS over the left DLPFC on Stroop
      task performance in healthy female volunteers was investigated. As expected,
      reaction time on both the incongruent and congruent trials decreased
      significantly after stimulation, and there was no difference with regard to the
      Stroop interference effect. Mood remained unchanged after rTMS. Such a pattern is
      consistent with the role of the left DLPFC in implementing top-down attentional
      control.

PMID- 16418844
TI  - Brain activity during visuomotor behavior triggered by arbitrary and spatially
      constrained cues: an fMRI study in humans.
AB  - Rule-based behavior associating nonspatial visual stimuli with learned responses
      is called arbitrary visuomotor mapping, an ability that enriches behavioral
      repertoire. To better understand the underlying neural correlates, the present
      functional magnetic resonance imaging (fMRI) study explored brain activity during
      visually informed movement involving two different types of cues and two
      different effectors. After being trained on the tasks, six healthy subjects
      performed right or left finger tapping tasks according to either arbitrary cues
      or spatially constrained cues. An event-related fMRI experiment was conducted on
      a 3-T MRI. The image data were analyzed with statistical parametric mapping. With
      the aid of the probabilistic architectonic map in the stereotaxic space, we
      identified three types of task-related brain activity: cue-selective, effector
      selective, and nonselective. The left ventrolateral prefrontal cortex and the
      rostral part of the right dorsal premotor cortex (PMd) exhibited cue-selective
      activity, which was greater during the arbitrary condition than the spatially
      constrained condition. The left ventral prefrontal activity may reflect retrieval
      of visuomotor association from memory in arbitrary context. The rostral part of
      the left PMd showed nonselective activity while the caudal part of the PMd on
      each side showed conspicuous effector-selective activity to the contralateral
      movement. These findings suggest functional demarcation of the PMd between its
      rostral and dorsal parts during visuomotor mapping.

PMID- 16418845
TI  - The effect of enslaving on perception of finger forces.
AB  - The primary purpose was to examine the effect of enslaving on finger force
      perception during isometric finger force production using an ipsilateral force
      matching paradigm. Fourteen subjects were instructed to produce varying levels of
      reference forces [10, 20, 30, and 40% maximal voluntary contraction (MVC)] force
      using one finger (index, I or little, L) and to reproduce these forces using the
      same finger (homo-finger tasks, I/I and L/L) or a different finger (hetero-finger
      tasks, I/L and L/I). Forces of all fingers were recorded. During homo-finger
      tasks, no differences were found in force magnitude or relative level of force
      (expressed as a proportion of MVC). The index finger matching force magnitudes
      were greater than the little finger reference force magnitudes, with
      significantly lower levels of relative force during L/I tasks; while the little
      finger matching forces underestimated the index finger reference forces with
      significantly higher levels of relative force during I/L tasks. The difference in
      the matching and reference forces by the instructed finger(s), i.e., matching
      error, was larger in hetero-finger tasks than in homo-finger tasks, particularly
      at high reference force levels (30, 40% MVC). When forces of all fingers were
      considered, enslaving (uninstructed finger forces) significantly minimized
      matching errors of the total force during both I/L and L/I hetero-finger tasks,
      especially at high reference force levels. Our results show that there is a
      tendency to match the absolute magnitude of the total force during ipsilateral
      finger force-matching tasks. This tendency is likely related to enslaving
      effects. Our results provide evidence that all (instructed and uninstructed)
      finger forces are sensed, thus resulting in perception of the absolute magnitude
      of total finger force.

PMID- 16418842
TI  - Upregulation of nestin, vimentin, and desmin in rat podocytes in response to
      injury.
AB  - Podocytes in the renal glomerulus express unusual intermediate filament (IF)
      proteins for epithelial cells. To gain insight into the role of IF proteins in
      podocytes, we investigated the expression of nestin, vimentin, and desmin in
      puromycin aminonucleoside (PAN) nephrosis. A Western blot analysis for nestin,
      vimentin, and desmin demonstrated their exclusive expression in glomeruli and
      showed their increase in expression in nephrotic glomeruli. Immunolocalization
      studies showed nestin and vimentin to be located predominantly in the podocytes
      in both normal and nephrotic glomeruli and that enhancement of desmin staining
      only occurred in podocytes. A ribonuclease protection assay showed high levels of
      vimentin and nestin expression in normal glomeruli and an upregulation of all
      three IF transcripts in nephrotic glomeruli. One day after the PAN injection,
      however, the vimentin transcripts were found to already have significantly
      increased, whereas those of nestin or desmin showed no such increase. These
      findings indicate that podocytes express three IF proteins, namely, vimentin,
      desmin, and nestin, which are differentially regulated in response to injury. An
      upregulation of IF proteins may increase the mechanical stability of cells, thus
      enabling podocytes to undergo morphological changes on the tensile glomerular
      capillary wall.

PMID- 16418846
TI  - Oculomotor responses to gradual changes in target direction.
AB  - Smooth pursuit tracking of targets moving linearly (in one dimension) is well
      characterized by a model where retinal image motion drives eye acceleration.
      However, previous findings suggest that this model cannot be simply extended to
      two-dimensional (2D) tracking. To examine 2D pursuit, in the present study, human
      subjects tracked a target that moved linearly and then followed the arc of a
      circle. The subjects' gaze angular velocity accurately matched target angular
      velocity, but the direction of smooth pursuit always lagged behind the current
      target direction. Pursuit speed slowly declined after the onset of the curve (for
      about 500 ms), even though the target speed was constant. In a second experiment,
      brief perturbations were presented immediately prior to the beginning of the
      change in direction. The subjects' responses to these perturbations consisted of
      two components: (1) a response specific to the parameters of the perturbation and
      (2) a nonspecific response that always consisted of a transient decrease in gaze
      velocity. With the exception of this nonspecific response, pursuit behavior in
      response to the gradual changes in direction and to the perturbations could be
      explained by using retinal slip (image velocity) as the input signal. The retinal
      slip was parallel and perpendicular to the instantaneous direction of pursuit
      ultimately resulted in changes in gaze velocity (via gaze acceleration). Perhaps
      due to the subjects' expectations that the target will curve, the sensitivity to
      the image motion in the direction of pursuit was not as strong as the sensitivity
      to image motion perpendicular to gaze velocity.

PMID- 16418847
TI  - Effect of cortical spreading depression on basal forebrain neurons.
AB  - During natural sleep and anesthesia, rhythmic hypo- and hyperpolarizations
      alternate in cortical pyramidal cells and are reflected as slow (<1 Hz) cortical
      rhythm at the level of the electroencephalogram (EEG). Membrane potential changes
      in pyramidal neurons were initially attributed to the rhythmic fluctuation of the
      cholinergic input as the basal forebrain (BF) neurons fire in synchrony with
      cortical waves, but a more recent proposal suggested that the slow rhythm was of
      cortical origin. In the present experiments, interaction between the cortex and
      the BF was examined in urethane-anesthetized rats. BF neuronal activity was
      inhibited by local infusion of lidocaine into the substantia innominata in one
      group of rats, while in another group, the slow cortical rhythm was blocked by
      inducing spreading depression (SD) in the cortex. Slow cortical rhythm persisted
      after unilateral lidocaine injection, but rhythmic firing in BF neurons
      disappeared following SD induction. These findings support the view that slow
      cortical rhythm is generated in the cortex and transmitted to the BF through
      descending fibers. According to anatomical data, these fibers can excite
      cholinergic cells only indirectly as they terminate on non-cholinergic neurons.
      Thus, timing of activity changes in BF neurons during the slow cortical rhythm
      might give some clue regarding their transmitter specificity.

PMID- 16418848
TI  - Cortical responses associated with predictable and unpredictable compensatory
      balance reactions.
AB  - This study investigated the effects of postural set on the cortical response
      evoked by an external perturbation to human upright stance. Postural set was
      manipulated by providing either predictable or unpredictable whole body
      perturbations which required balance corrections to maintain upright stability.
      Unpredictable perturbations evoked a large negative potential (e.g., CZ: -19.9+/
      5.1 microV) that was similar in timing (e.g., CZ: 98.9+/-5.5 ms) and shape to
      that reported in previous studies. This large negative potential was not
      discernable for perturbations with predictable onset timing and direction in
      spite of the presence of significant compensatory balance reactions. Importantly,
      when a surprise perturbation was presented following a series of predictable
      perturbations, the large negative potential occurred on this trial even though
      subjects expected a predictable stimulus onset. This suggests that the large
      negative potential was dependent on a dissociation between expected and actual
      stimuli rather than on a tonic central state defined by task conditions. These
      results suggest that cortical events may be linked to error detection that is
      independent of sensory or motor events associated with evoked balance reactions.

PMID- 16418849
TI  - Low frequency transcranial magnetic stimulation on the posterior parietal cortex
      induces visuotopically specific neglect-like syndrome.
AB  - The visuo-parietal (VP) region of the cerebral cortex is critically involved in
      the generation of orienting responses towards visual stimuli. In this study we
      use repetitive transcranial magnetic stimulation (rTMS) to unilaterally and non
      invasively deactivate the VP cortex during a simple spatial visual detection task
      tested in real space. Adult cats were intensively trained over 4 months on a task
      requiring them to detect and orient to a peripheral punctuate static LED
      presented at a peripheral location between 0 degrees and 90 degrees , to the
      right or left of a 0 degrees fixation target. In 16 different interleaved
      sessions, real or sham low frequency (1 Hz) rTMS was unilaterally applied during
      20 min (1,200 pulses) to the VP cortex. The percentage of mistakes detecting and
      orienting to contralateral visual targets increased significantly during the 15
      20 min immediately following real but not sham rTMS. Behavioral deficits were
      most marked in peripheral eccentricities, whereas more central locations were
      largely unaffected. Performance returned to baseline (pre-TMS) levels when
      animals were tested 45 min later and remained in pre-TMS levels 24 h after the
      end of the stimulation. Our results confirm that the VP cortex of the cat is
      critical for successful detection and orienting to visual stimuli presented in
      the corresponding contralateral visual field. In addition, we show that rTMS
      disrupts a robust behavioral task known to depend on VP cortex and does so for
      the far periphery of the visual field, but not for more central targets.

PMID- 16418850
TI  - A stimulus-dependent dissociation between the cerebral hemispheres under free
      viewing conditions.
AB  - Under free-viewing conditions, the leftward stimulus features are frequently
      overestimated (pseudoneglect). This asymmetry could reflect the operation of: (a)
      spatial attention mechanisms in the right hemisphere (RH) or, (b) stimulus
      specific activation. To test these propositions, we attempted to induce a
      stimulus-specific dissociation between the hemispheres under free-viewing
      conditions. In two experiments (n=23, n=22) dextrals carried out two tasks. The
      'grayscales' task required luminance judgments between two mirror-reversed
      luminance gradients. The flicker task required temporal frequency judgments
      between two mirror-reversed temporal gradients. The grayscales and flicker tasks
      suited the processing styles of the right and left hemispheres, respectively. For
      both experiments, a strong leftward bias was observed for the grayscales task,
      which could be the result of both of the mechanisms outlined above. In Experiment
      1, there was a rightward bias for the flicker task-but only for participants with
      longer reaction times. In Experiment 2, where all responses were delayed, a
      rightward bias was found for the flicker task for shorter stimuli. The data
      demonstrate that stimulus-specific dissociations can be induced under free
      viewing conditions. However, the fact that the rightward bias was: (a) weaker
      than the leftward bias and, (b) reduced by increases in length, demonstrates that
      RH spatial attention mechanisms are also important.

PMID- 16418851
TI  - Short latency crossed inhibitory reflex actions evoked from cutaneous afferents.
AB  - Although stimulation of cutaneous limb afferents has been shown to evoke crossed
      extension reflexes in unanaesthetised decerebrate or spinalised animals, here we
      show that stimulation of cutaneous nerves evokes crossed inhibition rather than
      excitation of contralateral extensor motoneurones in anaesthetised, spinal cord
      intact cats. Single pulse stimuli delivered to the saphenous, sural or
      superficial peroneal nerves evoked IPSPs in a high proportion of contralateral
      motoneurones including those of knee and ankle extensors. These IPSPs had
      thresholds of less than 1.5 times the threshold of the most excitable fibres and
      so large myelinated afferents contributed to them. The relative latencies of
      IPSPs evoked by stimulation of the contralateral superficial peroneal and sural
      nerves were longer than those evoked via ipsilateral pathways by approximately 1
      ms, suggesting that there are at least three synaptic relays in the crossed
      reflexes. The IPSPs evoked by stimulation of both ipsilateral and contralateral
      saphenous nerves had minimal latencies suggesting at least three synaptic delays.
      Like IPSPs evoked by group II afferents, the frequencies of occurrence of crossed
      IPSPs evoked by stimulation of cutaneous afferents were significantly reduced
      after spinal transection and the IPSPs recorded after spinalisation were
      significantly smaller. These findings are consistent with the recent proposal
      that dorsal horn neurones, which receive input from cutaneous afferents and
      contact premotor commissural interneurones may mediate the crossed inhibition.

PMID- 16418852
TI  - The role of eye movements in visuo-manual adaptation.
AB  - The present study evaluated the role of eye movements for manual adaptation to
      reversed vision. Subjects tracked a visual target using a mouse-driven cursor. In
      Experiment A, they were instructed to look at the target, look at the cursor,
      fixate straight ahead, or received no instructions regarding eye movements
      (Groups T, C, F, and N, respectively). Experiment B involved Groups T and C only.
      In accordance with literature, baseline manual tracking was more accurate when
      subjects were instructed to move their eyes rather than to fixate straight ahead.
      In contrast, no such benefit was observed for the adaptive improvement of
      tracking. We therefore concluded that transfer of information from the oculomotor
      to the hand motor system enhances the ongoing control of hand movements but not
      their adaptive modification; probably because the large computational demand of
      adaptation does not allow an additional processing of supplementary oculomotor
      signals. We further found adaptation to be worse in T than in any other group. In
      particular, adaptation was worse in T than in C although eye movements were the
      same: subjects in both groups moved their eyes in close relationship with the
      target rather than the cursor, Group C thus disobeying our instructions. The
      deficient performance of Group T is therefore not related to eye movements per
      se, but rather to our instructions. We conclude that an independently moving
      target strongly attracts eye movements independent of instruction (i.e. Groups T
      and C), but instructions may redirect spatially selective attention (i.e. Group T
      vs C), and thus influence adaptation.

PMID- 16418853
TI  - Influence of age and gender on the jaw-stretch and blink reflexes.
AB  - The aim of this study is to investigate the influence of age and gender on jaw
      stretch and blink reflexes (BR). Thirty "young" (26.5+/-0.7 years) and thirty
      "old" (47.8+/-1.8 years) healthy adults were included. Short-latency stretch
      reflex responses were evoked in the masseter and temporalis muscles by fast jaw
      stretches, and BR in orbicularis oculi muscle were evoked by painful electrical
      pulses (0.5 ms duration), delivered by a concentric electrode placed on the left
      lower forehead close to the supraorbital foramen. For the jaw-stretch reflex, the
      pre-stimulus EMG activity in the old subjects was significantly lower than that
      of the young subjects in the right and left masseter and temporalis muscles
      (P<0.006), whereas there was no difference in the results between males and
      females. The normalized peak-to-peak amplitude of the EMG in the left masseter
      and left and right temporalis muscles was significantly lower in the old subjects
      compared with the young subjects (P<0.02). Females had significantly higher
      normalized peak-to-peak EMG amplitudes compared with males in the right masseter
      and left temporalis muscles (P<0.05). The old subjects had significantly lower
      root mean square (RMS) (P=0.01) and average (P<0.02) BR values in the right and
      left orbicularis oculi muscles, and lower area under the curve (AUC) (P=0.02)
      values in the left orbicularis oculi muscle compared with the young subjects.
      Female subjects had significantly lower AUC (P=0.02) in the left orbicularis
      oculi muscle compared with males. The old subjects had significantly later offset
      (P<0.003) and longer duration (P<0.001) in the left orbicularis oculi compared
      with the young subjects. The results of the present study demonstrated a
      significant effect of both age and gender on stretch and BR and suggested that
      these variables should be taken into consideration in the interpretation of
      brainstem reflexes in basic and clinical studies.

PMID- 16418854
TI  - Tiagabine and vigabatrin reduce the severity of NMDA-induced excitotoxicity in
      chick retina.
AB  - The possible neuroprotective effects of two GABAergic drugs, tiagabine (TGB) and
      vigabatrin (VGB), against N-methyl-D-aspartate (NMDA)-induced excitotoxicity have
      been investigated in the isolated chick embryo retina model. Retina segments were
      incubated either with NMDA alone (100 microM) or with NMDA and TGB or VGB (10
      1,000 microM, added 5 min before NMDA). Retina damage was assessed after 24 h by
      measuring lactate dehydrogenase (LDH) activity present in the medium and by
      histological analysis. Both drugs reduced LDH release in a dose-dependent manner
      with comparable mean maximal values of 56.6-63.7% achieved at concentration of 1
      mM. Histological analysis of retina slices was in line with the biochemical
      assays and showed partial preservation of drug exposed retina structure with
      reduced edema especially in the inner plexiform layer. The present data provide
      pharmacological evidence that both TGB and VGB reduce the severity of NMDA
      induced excitotoxic damage. Although an increase in GABAergic transmission might
      play a role, this in itself is insufficient to explain the neuroprotective effect
      of the two drugs and the exact mechanism remains to be elucidated.

PMID- 16418855
TI  - Altered timing of postural reflexes contributes to falling in persons with
      chronic stroke.
AB  - The purpose of this study was to determine differences in the timing of postural
      reflexes and changes in kinematics between those who fell (fallers) in response
      to standing platform translations and those who did not (non-fallers). Forty-four
      persons with stroke were exposed to unexpected forward and backward platform
      translations while standing. Surface electromyography from bilateral tibialis
      anterior, gastrocnemius, rectus femoris, and biceps femoris were recorded along
      with kinematic data. Those that fell in response to the translations were
      compared to those who did not fall in terms of (1) postural reflex onset latency,
      (2) the time interval between the activation of distal and proximal muscles (i.e.
      intralimb coupling), and (3) changes in joint angles and trunk motion.
      Approximately 85% of falls occurred in response to the forward translations.
      Postural reflex onset latencies were delayed and intralimb coupling durations
      were longer in the faller versus non-faller group. At the time that the platform
      completed the translating motion (300 ms), the faller group demonstrated higher
      trunk velocity, greater change in paretic ankle angle, and the trunk was further
      behind the ankle compared to the non-faller group. This study suggests that
      following platform translations, delays in the timing of postural reflexes and
      disturbed intralimb coupling result in changes in kinematics, which contribute to
      falls in persons with stroke.

PMID- 16418857
TI  - Vocal communication in adult greater horseshoe bats, Rhinolophus ferrumequinum.
AB  - Whereas echolocation in horseshoe bats is well studied, virtually nothing is
      known about characteristics and function of their communication calls. Therefore,
      the communication calls produced by a group of captive adult greater horseshoe
      bats were recorded during various social interactions in a free-flight facility.
      Analysis revealed that this species exhibited an amazingly rich repertoire of
      vocalizations varying in numerous spectro-temporal aspects. Calls were classified
      into 17 syllable types (ten simple syllables and seven composites). Syllables
      were combined into six types of simple phrases and four combination phrases. The
      majority of syllables had durations of more than 100 ms with multiple harmonics
      and fundamental frequencies usually above 20 kHz, although some of them were also
      audible to humans. Preliminary behavioral observations indicated that many calls
      were emitted during direct interaction with and in response to social calls from
      conspecifics without requiring physical contact. Some echolocation-like
      vocalizations also appeared to clearly serve a communication role. These results
      not only shed light upon a so far widely neglected aspect of horseshoe bat
      vocalizations, but also provide the basis for future studies on the neural
      control of the production of communicative vocalizations in contrast to the
      production of echolocation pulse sequences.

PMID- 16418856
TI  - An improved purification procedure for the soluble [NiFe]-hydrogenase of
      Ralstonia eutropha: new insights into its (in)stability and spectroscopic
      properties.
AB  - Infrared (IR) spectra in combination with chemical analyses have recently shown
      that the active Ni-Fe site of the soluble NAD(+)-reducing [NiFe]-hydrogenase from
      Ralstonia eutropha contains four cyanide groups and one carbon monoxide as
      ligands. Experiments presented here confirm this result, but show that a variable
      percentage of enzyme molecules loses one or two of the cyanide ligands from the
      active site during routine purification. For this reason the redox conditions
      during the purification have been optimized yielding hexameric enzyme
      preparations (HoxFUYHI(2)) with aerobic specific H(2)-NAD(+) activities of 150
      185 mumol/min/mg of protein (up to 200% of the highest activity previously
      reported in the literature). The preparations were highly homogeneous in terms of
      the active site composition and showed superior IR spectra. IR spectro
      electrochemical studies were consistent with the hypothesis that only reoxidation
      of the reduced enzyme with dioxygen leads to the inactive state, where it is
      believed that a peroxide group is bound to nickel. Electron paramagnetic
      resonance experiments showed that the radical signal from the NADH-reduced enzyme
      derives from the semiquinone form of the flavin (FMN-a) in the hydrogenase module
      (HoxYH dimer), but not of the flavin (FMN-b) in the NADH-dehydrogenase module
      (HoxFU dimer). It is further demonstrated that the hexameric enzyme remains
      active in the presence of NADPH and air, whereas NADH and air lead to rapid
      destruction of enzyme activity. It is proposed that the presence of NADPH in
      cells keeps the enzyme in the active state.

PMID- 16418858
TI  - Mapping QTLs that control the performance of rice tissue culture and evaluation
      of derived near-isogenic lines.
AB  - Quantitative trait loci (QTLs) that control the performance of tissue culture in
      rice were detected by using 116 RFLP markers and 183 BC1F3 lines derived from two
      varieties, Koshihikari and Kasalath. With time, the seed callus of Koshihikari
      tends to turn brown and stop growing, while that of Kasalath remains yellowish
      white and proliferates continuously. The performance of tissue culture in the
      induction of calli from seed, the subculture of induced calli, and shoot
      regeneration were evaluated by five indices: induced-callus weight, induced
      callus color, subcultured-callus volume, subcultured-callus color, and
      regeneration rate. Through callus induction and subculture, eight putative QTLs
      (P < 0.001) were located on chromosomes 1, 4, and 9. Among these QTLs, five
      Kasalath alleles and three Koshihikari alleles improved tissue culture
      performance. No QTL for regeneration was found. Among all the QTLs, qSv1
      explained the largest phenotypic variance, 33%, in subcultured-callus volume. In
      induced-callus color, two detected QTLs accounted for 36.4% of the total
      phenotypic variance; this was the highest score among the five indices used to
      evaluate the performance of tissue culture. Three near-isogenic lines for QTLs,
      located in two regions on chromosome 1, were developed to evaluate their tissue
      culture performance. The Kasalath alleles in qSv1 and qSc1-1 improved callus
      color through callus induction and subculture, and increased the subcultured
      callus volume and the fresh weight of regenerated calli, including shoots, roots,
      and differentiated structures. In qSc1-2, the Kasalath allele improved callus
      color through induction and subculture. These results verified the presence of
      QTLs for the volume and color of subcultured callus on chromosome 1, qSv1, qSc1
      1, and qSc1-2.

PMID- 16418859
TI  - [Benign and malignant lesions in the region of the inner ear and cerebellopontine
      angle].
AB  - Tumorous lesions in the region of the inner ear and cerebellopontine angle are
      very rare and can be classified into benign and malignant disease forms. This
      contribution presents and explains the CT and MRI characteristics of these
      tumors.High-resolution computed tomography (HRCT) in the axial projection is
      applied for evaluation in the high-resolution bone window. The coronary slices
      can be reconstructed from the axial datasets or in individual cases examined in
      the coronary plane.HRCT excellently demonstrates osseous lesions and in
      individual cases - e.g., exostoses - it can simply suffice to perform HRCT of the
      temporal bone, while HRCT is also excellent for detecting osseous lesions to
      determine whether the tumor is benign or malignant.MRI, on the other hand,
      excellently shows the extent of tumor spread because of its superb soft tissue
      contrast. Consequently, HRCT and MRI images of the inner ear and cerebellopontine
      angle provide meaningful information for visualization and classification of
      tumorous lesions. The two methods should not be considered as competing but
      rather as complementary and among other aspects exert considerable influence on
      the therapeutic approach.

PMID- 16418860
TI  - Bacillus thuringiensis protein production, signal transduction, and insect
      control in chemically inducible PR-1a/cry1Ab broccoli plants.
AB  - In an effort to develop a chemically inducible system for insect management, we
      studied production of Cry1Ab Bacillus thuringiensis (Bt) protein and control of
      the diamondback moth (DBM), Plutella xylostella L., in inducer-treated and
      untreated tissues of a broccoli line transformed with a PR-1a/cry1Ab expression
      cassette. Spraying leaves of these plants with the inducer acibenzolar-S-methyl
      (= 1,2,3 benzothiadiazole-7-thiocarboxylic acid-S-methyl-ester) (ASM) triggered
      expression of the cry1Ab gene and produced a high level of Cry1Ab protein within
      2-3 days. Cry1Ab protein persisted in leaves for at least 8 weeks, providing
      prolonged protection from P. xylostella attack. Signals generated in inducer
      treated leaves were transferred to untreated newly emerged leaves or heads, as
      seen by production of Cry1Ab protein and/or protection from insect damage in
      these plant parts. Signal transduction proceeded in an attenuated manner up to
      the sixth newly emerged leaf. No Cry1Ab protein was detectable by ELISA in
      uninduced young leaves, but small amounts of the protein were present in
      uninduced leaves older than 3 weeks and caused some insect mortality. Such basal
      expression of Bt genes without induction may favor the evolution of resistant
      insect populations and therefore limits the application of the PR-1a/cry1Ab
      system for insect management. However, the rapid production and steady
      maintenance of a high level of transgenic protein upon induction, the signal
      transduction observed, and the fact that the chemical inducer can be used in
      field conditions make the PR-1a promoter attractive for chemical regulation of
      other agriculturally or pharmaceutically important genes for which low expression
      in the absence of induction is not a concern.

PMID- 16418861
TI  - Tissue culture and transient transformation of Marestail (Conyza canadensis (L.)
      Cronquist).
AB  - Glyphosate resistant crops are useful to agriculture by facilitating the use of
      nonselective herbicides, such as RoundUp, that have low human and environmental
      toxicity. The occurrence of glyphosate resistant weeds, however, has raised
      concern about the future utility of these crops. Conyza canadensis (L.) Cronquist
      (marestail or horseweed) is one such glyphosate resistant weed that has yet to be
      fully analyzed or established in tissue culture. Tissue culture enables the
      examination of physiological characteristics of a plant in an aseptic and
      controlled environment. For the present study, mairstail was cultured on a
      Murashige and Skoog based medium supplemented with 6-benzylaminopurine, and alpha
      naphthaleneacetic acid. Plant regeneration was achieved on the same basal medium
      supplemented with only gibberellic acid. Glyphosate resistance could be
      demonstrated in the cultured tissues. The cultures could also be transformed with
      Agrobacterium tumefaciens without chemically inducing virulence using phenolics
      or glucose and resulting in a transformation frequency (transgenic events per
      total number of explants used) of about 13%. The tissue culture growth,
      preliminary glyphosate resistance data and genetic transformation data gathered
      in this project provide the means to further evaluate the mode of glyphosate
      resistance expressed by marestail.

PMID- 16418862
TI  - Cluster analysis of signal-intensity time course in dynamic breast MRI: does
      unsupervised vector quantization help to evaluate small mammographic lesions?
AB  - We examined whether neural network clustering could support the characterization
      of diagnostically challenging breast lesions in dynamic magnetic resonance
      imaging (MRI). We examined 88 patients with 92 breast lesions (51 malignant, 41
      benign). Lesions were detected by mammography and classified Breast Imaging and
      Reporting Data System (BIRADS) III (median diameter 14 mm). MRI was performed
      with a dynamic T1-weighted gradient echo sequence (one precontrast and five
      postcontrast series). Lesions with an initial contrast enhancement >or=50% were
      selected with semiautomatic segmentation. For conventional analysis, we
      calculated the mean initial signal increase and postinitial course of all voxels
      included in a lesion. Secondly, all voxels within the lesions were divided into
      four clusters using minimal-free-energy vector quantization (VQ). With
      conventional analysis, maximum accuracy in detecting breast cancer was 71%. With
      VQ, a maximum accuracy of 75% was observed. The slight improvement using VQ was
      mainly achieved by an increase of sensitivity, especially in invasive lobular
      carcinoma and ductal carcinoma in situ (DCIS). For lesion size, a high
      correlation between different observers was found (R(2) = 0.98). VQ slightly
      improved the discrimination between malignant and benign indeterminate lesions
      (BIRADS III) in comparison with a standard evaluation method.

PMID- 16418863
TI  - Effective radiation doses in CT colonography: results of an inventory among
      research institutions.
AB  - The purpose of this study was to estimate the effective dose that is currently
      used in CT colonography using scan parameters that were collected for this
      purpose, and to investigate trends in time. PubMed was systematically searched
      from 1996 until January 2004 for studies investigating CT colonography. Research
      institutions were contacted and asked for their current scan protocol. Thirty-six
      institutions published 74 studies. Twenty-eight of the 36 institutions provided
      their current protocol. The median effective dose in 2004 was 5.1 mSv (range 1.2
      11.7 mSv) per position. Most institutions (93%) scan in both the supine and prone
      positions. The median mAs value was 67 mAs (range 20-200), median collimation was
      2.5 mm (range 0.75-5). From 1996 until 2004 a significant decrease in mAs and
      collimation (P=0.006, P<0.0001, respectively) was observed, while institutions
      that used a multislice scanner increased (P<0.0001). The effective dose remained
      constant (P=0.76). In 2004 the median effective dose for a complete CT
      colonography was 10.2 mSv. Despite the increasing use of multislice scanners,
      which are slightly less dose-efficient, the median effective dose remained
      approximately constant between 1996 and 2004. This is mainly caused by the use of
      lower mAs settings.

PMID- 16418865
TI  - [Disease sequelae].

PMID- 16418864
TI  - Differential CT features of infectious pneumonia versus bronchioloalveolar
      carcinoma (BAC) mimicking pneumonia.
AB  - The purpose of this study was to evaluate retrospectively the differential CT
      features of bronchioloalveolar carcinoma (BAC) mimicking pneumonia and infectious
      pneumonia at the lung periphery. CT images were reviewed in 47 patients with
      focal areas of parenchymal opacification at the lung periphery. We evaluated the
      presence of ground-glass attenuation, marginal conspicuity of the lesion, CT
      angiogram sign, air-bronchogram sign, a bubble-like low-attenuation area within
      the lesion, presence of pleural thickening and retraction associated with the
      lesion, presence of pleural effusion and extra-pleural fatty hypertrophy,
      presence of bronchial wall thickening proximal to the lesion, and air-trapping in
      the normal lung near the lesion. BAC (n=18) depicted the presence of a bubble
      like low-attenuation area within the lesion, whereas infectious pneumonia (n=29)
      represented the pleural thickening associated with the lesion and bronchial wall
      thickening proximal to the lesion (P<0.05). The other CT findings showed no
      significant differences (P>0.05). The focal areas of the parenchymal
      opacification on the CT images may suggest infectious pneumonia rather than BAC
      when they show bronchial wall thickening proximal to the lesion and pleural
      thickening associated with the lesion, whereas BAC is characterized as the
      presence of a bubble-like low attenuation area within the tumor.

PMID- 16418866
TI  - [Pharmacological therapy for ventricular arrhythmias: evidence for current
      treatment strategies and perspectives for the future].
AB  - This review summarizes the current status of pharmacological therapy for
      ventricular arrhythmias in symptomatic patients. The selection of specific drugs
      for this indication is highly dependent on the underlying heart disease. In
      primary prevention of sudden death, antiarrhythmic agents do not play a role-
      except betareceptor antagonists. Similarly, in patients treated for secondary
      prevention of cardiac arrest or hemodynamically symptomatic ventricular
      tachycardia, the implantable defibrillator constitutes the therapy of choice with
      hardly any role left for antiarrhythmic drugs. An emerging role for
      antiarrhythmic drug therapy is represented by the concomitant pharmacological
      treatment in ICD recipients who experience shocks from their devices (hybrid
      therapy). Several randomized clinical trials have recently evaluated this issue
      and permit an evidence-based treatment strategy. Currently, most patients receive
      sotalol or amiodarone for hybrid therapy with azimilide as a potential new class
      III antiarrhythmic drug for this treatment indication.

PMID- 16418867
TI  - Cuts can kill: the roles of apoptotic nucleases in cell death and animal
      development.
AB  - Chromosome fragmentation is one of the major biochemical hallmarks of apoptosis.
      However, until recently, its roles in apoptosis and mechanisms of action remained
      elusive. Recent biochemical and genetic studies have shown that chromosome
      fragmentation is a complex biochemical process that involves a plethora of
      conserved nucleases with distinct nuclease activities and substrate
      specificities. These apoptotic nucleases act cooperatively among themselves and
      with other nonnuclease cofactors to promote stepwise chromosome fragmentation and
      DNA degradation. Importantly, in addition to its direct contribution to the
      dismantling of the dying cell, apoptotic DNA degradation can facilitate cell
      killing and other apoptotic events such as clearance of apoptotic cells.
      Furthermore, some apoptotic nucleases apparently affect other aspects of animal
      development, including immune responses. The identification of new apoptotic
      nucleases and analysis of their functions in apoptosis and animal development
      should pave the way for future studies to uncover new functions for apoptotic
      nucleases and shed light on the hidden links between apoptotic DNA degradation
      and human diseases.

PMID- 16418868
TI  - Pipecolic acid in microbes: biosynthetic routes and enzymes.
AB  - Pipecolic acid is an important precursor of many useful microbial secondary
      metabolites. Pipecolic acid-derived moieties are often crucial for the biological
      activities of some microbial natural products with pharmaceutical applications.
      Understanding the biogenesis of pipecolic acid in microorganisms would be a
      significant step toward the mutasynthesis of novel analogs of choice. This review
      focuses on various microbial pathways and enzymes for pipecolic acid synthesis,
      especially those related to the origination of pipecolic acid moieties in
      secondary metabolites.

PMID- 16418869
TI  - Marcel Faber Roundtable: is our antibiotic pipeline unproductive because of
      starvation, constipation or lack of inspiration?
AB  - There are few new antibiotics in the pipeline today. The reasons may include
      starvation at the front of the pipeline due to inadequate sources of suitable
      compounds to screen coupled with poorly validated discovery methodologies. A
      successful antibiotic discovery approach in the past, based upon whole cell
      antibiotic screening of natural products from actinomycetes and fungi, eventually
      suffered from constipation in the middle of the pipeline due to rediscovery of
      known compounds, even though low throughput methodology was employed at the front
      end. The current lack of productivity may be attributed to the poor choice of
      strategies to address the discovery of new antibiotics. Recent applications of
      high throughput in vitro screening of individual antibacterial targets to
      identify lead compounds from combinatorial chemical libraries, traditional
      chemical libraries, and partially purified natural product extracts has not
      produced any significant clinical candidates. The solution to the current dilemma
      may be to return to natural product whole cell screening. For this approach to
      work in the current millennium, the process needs to be miniaturized to increase
      the throughput by orders of magnitude over traditional screening, and the
      rediscovery of known antibiotics needs to be minimized by methods that can be
      readily monitored and improved over time.

PMID- 16418870
TI  - Colanic acid is an exopolysaccharide common to many enterobacteria isolated from
      paper-machine slimes.
AB  - In this study, polysaccharide-producing bacteria were isolated from slimes
      collected from two Finnish and one Spanish paper mill and the exopolysaccharides
      (EPSs) produced by 18 isolates were characterised. Most of the isolates, selected
      on the bases of slimy colony morphology, were members of the family
      Enterobacteriaceae most frequently belonging to the genera Enterobacter and
      Klebsiella including Raoultella. All of the EPSs analysed showed the presence of
      charged groups in the form of uronic acid or pyruvate revealing the polyanionic
      nature of these polysaccharides. Further results of the carbohydrate analysis
      showed that the EPS produced by nine of the enterobacteria was colanic acid.

PMID- 16418871
TI  - AcSDKP: a new potential marker of malignancy of the thyroid gland.
AB  - BACKGROUND AND AIMS: The tetrapeptide Acetyl-Ser-Asp-Lys-Pro (AcSDKP) a
      physiologic inhibitor of stem-cell proliferation is also known for it's strong
      angiogenic activity. It has been shown that blood levels of this peptide are
      increased in some hematological malignancies. However, no data on the
      concentration of AcSDKP present in solid tumor tissue are available. The aim of
      our study was to measure tissue concentration of AcSDKP in benign and malignant
      lesions of the thyroid gland. PATIENTS AND METHODS: We assessed AcSDKP level in
      thyroid tissue specimens using enzyme immunoassay kit. The specimens were taken
      intraoperatively from 20 patients (17 women and 3 men aged 21-68 years): 10
      patients with benign nodular goiter and 10 patients with papillary carcinoma of
      the thyroid gland. RESULTS: The obtained results show that tissue concentration
      of AcSDKP in malignant thyroid tumors is five times higher when compared to
      benign lessions. CONCLUSION: We conclude that AcSDKP may play a role in the
      development of the thyroid gland lesions. However, the further investigations
      concerning the tetrapeptide concentration in other thyroid malignancies, toxic
      nodular, and Grave's goiter are required to conclude on the eventual use of
      AcSDKP as a marker of malignancy.

PMID- 16418872
TI  - Preliminary experience with a terpene mixture versus ibuprofen for treatment of
      category III chronic prostatitis/chronic pelvic pain syndrome.
AB  - To evaluate the efficacy of a terpene mixture (rowatinex) compared to ibuprofen,
      patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were
      randomly selected to either receive rowatinex 200 mg t.i.d. or ibuprofen 600 mg
      t.i.d. After a 6-week treatment, the decrease in the mean total NIH-CPSI score
      was significant in both groups from 21.4 to 15.3, (6.1 (p < 0.01) and from 21.2
      to 16.8, (4.4 (p = 0.04) in the rowatinex and ibuprofen group, respectively. The
      rate of definite improvement as defined as 25% improvement in the total score was
      superior (p = 0.04) in the rowatinex group (68%) versus the ibuprofen group
      (40%). Judging from these results, rowatinex gave significant symptomatic relief
      and may be of benefit for many men diagnosed with CP/CPPS. Further, including the
      placebo-controlled studies are necessary to define its role in the management of
      this difficult to treat disease.

PMID- 16418873
TI  - The efficacy of human schistosomicide treatment may depend on the rate of
      transmission.
AB  - The efficacy of different treatment protocols in humans infected with Schistosoma
      mansoni at sites with different transmission conditions was evaluated by the
      disappearance of anti-worm intestine IgM antibodies in an indirect fluorescence
      antibody test (IgM-IFT) and anti-egg antibodies in the circumoval precipitin test
      (COPT). Patient sera coming from sites of active low transmission (ALT), active
      high transmission (AHT) and low interrupted transmission (LIT) from Venezuela
      were studied. Chemotherapy protocols were (1) ALT, 60 mg/kg praziquantel (Pzq60);
      (2) AHT, one dose of 40 mg/kg Pzq followed by one dose of 20 mg/kg oxamniquine
      for one group and one dose of 40 mg/kg Pzq alone for the other group; (3) LIT,
      one dose of 40 mg/kg Pzq repeated every 3 months up to three doses. Cure rates
      occurred mostly between 3 and 12 months with the exception of Pzq60-ALT where it
      was evident before 3 months. Higher cure rates were evident in both places of low
      transmission (ALT and LIT) and the lowest in the AHT regardless of the treatment
      protocol. Cure was more evident with COPT compared to IgM-IFT. The rate of
      serological cure appears then to depend on the previous state of transmission.
      The differential cure rate evaluated by both techniques is probably due to the
      persistence of antibodies against antigens in different stages of the parasite.

PMID- 16418874
TI  - Biliary excretion of etoposide in children with cancer.
AB  - PURPOSE: Two children with soft tissue sarcomas receiving etoposide as part of
      their standard clinical treatment had external biliary drainage due to
      obstruction of the bile duct. These unusual cases provided an opportunity to
      investigate the biliary clearance of etoposide by determining etoposide
      concentrations in bile and plasma samples obtained during chemotherapy. PATIENTS
      AND METHODS: Etoposide was administered to patient 1 at a dose of 150 mg/m(2), as
      a 4 h infusion, on each of three days of treatment. Patient 2 received a daily
      etoposide dose of 800 mg/m(2) as a 24 h continuous infusion, also over a 3-day
      treatment period. Bile and plasma samples were obtained at regular intervals from
      both patients and etoposide levels quantified by LC/MS analysis. RESULTS AND
      DISCUSSION: Biliary etoposide clearance was approximately equal to the flow of
      bile, with an average clearance of 0.32 ml/min determined in patient 1. Less than
      2% of the etoposide dose administered was excreted in the bile in either patient
      studied, indicating that biliary clearance of etoposide is relatively minor.
      These results suggest that etoposide dose adjustment is unnecessary in patients
      with biliary obstruction.

PMID- 16418875
TI  - Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or
      capecitabine.
AB  - AIM: 5-fluorouracil (5-FU) and its prodrug capecitabine are cardiotoxic. This
      retrospective study aimed to identify risk factors and to give practical measures
      to make such chemotherapy feasible if cardiotoxicity occur. METHOD: Review of
      cardiotoxicity among 668 patients treated with 5-FU or capecitabine for
      gastrointestinal cancers. RESULTS: Cardiotoxicity occurred in 29 cases (4.3%).
      The number of cases according to cardiotoxicity CTC grades 2-4 for patients with
      and without pre-existing cardiovascular disease were none, 10, and 2 cases, and
      3, 14, and no cases, respectively (P=0.16). In three patients intercurrent
      decrease of renal clearances to <30, 48 and 71 ml min(-1) led to markedly
      increased cardiotoxicity. Chemotherapy dose reduction to 70 or 50%, either alone
      or in addition to antiangina medication prevented cardiotoxicity during
      subsequent chemotherapy in nine (60%) and three (20%) cases out of 15 assessable
      patients (P=0.001), respectively. To abolish symptoms of cardiotoxicity,
      sublingual nitroglycerine was efficient for 15 patients and inefficient for two
      (P=0.001). CONCLUSION: Cardiac and renal co-morbidity are risk factors for 5-FU
      induced cardiotoxicity. In this situation, rechallenge with modified 5-FU-based
      chemotherapy regimen supported by symptomatic medical treatment is feasible.

PMID- 16418878
TI  - De novo COX2 mutation in a LHON family of Caucasian origin: implication for the
      role of mtDNA polymorphism in human pathology.
AB  - Recent studies suggest that certain mutations with phylogeographic importance as
      haplogroup markers may also influence the phenotypic expression of particular
      mitochondrial disorders. One such disorder, Leber's hereditary optic neuropathy
      (LHON), demonstrates a clear expression bias in mtDNAs belonging to haplogroup J,
      a West Eurasian maternal lineage defined by polymorphic markers that have been
      called 'secondary' disease mutations. In this report, we present evidence for a
      de novo heteroplasmic COX2 mutation associated with a LHON clinical phenotype.
      This particular mutation-at nucleotide position 7,598-occurs in West Eurasian
      haplogroup H, the most common maternal lineage among individuals of European
      descent, whereas previous studies have detected this mutation only in East
      Eurasian haplogroup E. A review of the available mtDNA sequence data indicates
      that the COX2 7598 mutation occurs as a homoplasic event at the tips of these
      phylogenetic branches, suggesting that it could be a variant that is rapidly
      eliminated by selection. This finding points to the potential background
      influence of polymorphisms on the expression of mild deleterious mutations such
      as LHON mtDNA defects and further highlights the difficulties in distinguishing
      deleterious mtDNA changes from neutral polymorphisms and their significance in
      the development of mitochondriopathies.

PMID- 16418877
TI  - [Massive transaminase rise after vicryl mesh wrapping for liver trauma].
AB  - Mesh wrapping hepatorrhaphy is an established method to control severe hepatic
      bleeding after trauma. Besides the multiple advantages of this technique, only a
      few complications are described in literature. We report a patient with severe
      liver trauma showing ischemia of the liver caused by post-traumatic edema and
      compression of the liver after mesh wrapping hepatorraphy to control the
      bleeding. To avoid this complication, early and frequent control of liver enzymes
      is highly recommended and, in case of elevation, laparotomy and decompression
      should be performed.

PMID- 16418876
TI  - [Prophylactic parathyroidectomy for familial parathyroid carcinoma].
AB  - In contrast to primary hyperparathyroidism, parathyroid carcinoma is a rare
      disease. In patients with hyperparathyroidism jaw tumor (HPT-JT) syndrome, caused
      by germline mutations in HRPT2, the development of parathyroid carcinoma is
      estimated to be 10-15%. This review summarizes the clinical and molecular genetic
      data of about 100 patients in the literature and three of our own cases.
      Unfortunately, osteofibromas, which might enable timely diagnosis of HPT-JT
      syndrome, occur in only about 30% of patients; about 80% have uniglandular
      disease. Based on the current data, a general recommendation to perform
      prophylactic parathyroidectomy cannot be given. However, thorough screening of
      patients at risk is mandatory. Of note in patients thought to have sporadic
      parathyroid carcinoma, germline HRPT2 mutations are found in up to 20%. Hence,
      any patient with parathyroid carcinoma should undergo HRPT2 mutation analysis.

PMID- 16418879
TI  - Low genetic diversity and biased distribution of mitochondrial DNA haplotypes in
      the Japanese macaque (Macaca fuscata yakui) on Yakushima Island.
AB  - The Japanese macaques (Macaca fuscata yakui) on Yakushima Island are an endemic
      subspecies and are closely related to the population of Kyushu, one of the main
      islands of Japan. Using feces collected throughout Yakushima Island, we examined
      mitochondrial DNA (mtDNA) to investigate the phylogeography of Japanese macaques.
      Six haplotypes were observed for a 203-bp fragment of the mtDNA control region.
      The nucleotide diversity (pi) was low (0.0021). The genetic divergence within the
      Yakushima population was lower (0.009) than that among four haplotypes of the
      Kyushu population (0.015), calculated using Kimura's two-parameter method. The
      mismatch distribution analysis of the six haplotypes of the Yakushima population
      suggested that the Yakushima population had experienced a sudden expansion in
      population size, which could be related to the bottleneck effect. The geographic
      distribution of the mtDNA haplotypes was not uniform. One haplotype was
      distributed widely, whereas the other five haplotypes were distributed only in
      the lowlands. The low genetic diversity and biased distribution are discussed in
      relation to an environmental crash caused by ancient volcanic activity near this
      island, which is postulated to have happened about 7,300 years ago, and the
      delayed recovery of highland vegetation.

PMID- 16418881
TI  - Morphometry of the external ear in our adult population.
AB  - This study aimed to determine the mean values of the different morphometric
      measurements from right and left ears. These measurements were taken from 341
      healthy young adults (150 women and 191 men) ages 18 to 25 years using an
      electronic digital caliper. The results showed the mean values for total ear
      height, lobular height and width, distances from tragus to antihelix and to
      helix, and ear projection and width to be, respectively, 59.7 +/- 3 mm, 17.5 +/-
      1.4 mm, 18.5 +/- 2.2 mm, 16.6 +/- 1.7 mm, 25.1 +/- 2 mm, 16.6 +/- 2 mm, and 31.3
      +/- 2.2 mm for the left ear, and 59.5 +/- 3.1 mm, 17.9 +/- 1.5 mm, 18.9 +/- 2 mm,
      16.5 +/- 1.8 mm, 25.2 +/- 1.9 mm, 17 +/- 1.9 mm, and 31.2 +/- 2.2 mm for the
      right ear in the young women. However, in the young men, these values were,
      respectively, 63.1 +/- 3.6 mm, 18.3 +/- 1.7 mm, 19.4 +/- 2 mm, 17.2 +/- 1.8 mm,
      26.3 +/- 1.9 mm, 17 +/- 2.3 mm, and 33.3 +/- 2.2 mm for the left ear, and 62.9 +/
      3.5 mm, 18.4 +/- 1.7 mm, 19.8 +/- 1.9 mm, 17.2 +/- 1.8 mm, 26.6 +/- 1.9 mm, 17.6
      +/- 2.1 mm, and 33.1 +/- 2.1 mm for the right ear.

PMID- 16418882
TI  - A multi-institutional phase II trial of preoperative full-dose gemcitabine and
      concurrent radiation for patients with potentially resectable pancreatic
      carcinoma.
AB  - BACKGROUND: We report the results of a multi-institutional phase II trial that
      used preoperative full-dose gemcitabine and radiotherapy for patients with
      potentially resectable pancreatic carcinoma. METHODS: Patients were treated
      before surgery with three cycles of full-dose gemcitabine (1000 mg/m2
      intravenously), with radiation during the second cycle (36 Gy in daily 2.4-Gy
      fractions). Patients underwent surgery 4 to 6 weeks after the last gemcitabine
      infusion. RESULTS: There were 10 men and 10 women, with a median age of 58 years
      (range, 50-80 years). Nineteen patients (95%) completed therapy without
      interruption, and one experienced grade 3 gastrointestinal toxicity. The mean
      weight loss after therapy was 4.0%. Of 20 patients taken to surgery, 17 (85%)
      underwent resections (16 pancreaticoduodenectomies and 1 distal pancreatectomy).
      The complication rate was 24%, with an average length of stay of 13.5 days. There
      were no operative deaths. Pathologic analysis revealed clear margins in 16 (94%)
      of 17 and uninvolved lymph nodes in 11 (65%) of 17 specimens. One specimen
      contained no residual tumor, and three specimens revealed only microscopic foci
      of residual disease. With a median follow-up of 18 months, 7 (41%) of the 17
      patients with resected disease are alive with no recurrence, 3 (18%) are alive
      with distant metastases, and 7 (41%) have died. CONCLUSIONS: Preoperative
      gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi
      institutional setting. This protocol had a high rate of subsequent resection,
      with acceptable morbidity. The high rate of negative margins and uninvolved nodes
      suggests a significant tumor response. Preliminary survival data are encouraging.
      This regimen should be considered in future neoadjuvant trials for pancreatic
      cancer.

PMID- 16418883
TI  - [11C]metahydroxyephedrine and [18F]fluorodeoxyglucose positron emission
      tomography improve clinical decision making in suspected pheochromocytoma.
AB  - BACKGROUND: Pheochromocytomas are rare tumors of chromaffin cells for which the
      optimal management is surgical resection. Precise diagnosis and localization may
      be elusive. We evaluated whether positron emission tomography (PET) scanning with
      the combination of [18F]fluorodeoxyglucose (FDG) and the norepinephrine analogue
      [11C]metahydroxyephedrine (mHED) would allow more exact diagnosis and
      localization. METHODS: Fourteen patients with suspected pheochromocytoma were
      evaluated by anatomical imaging (computed tomography or magnetic resonance
      imaging) and [131I]metaiodobenzylguanidine (MIBG) planar imaging. PET imaging was
      performed by using mHED with dynamic adrenal imaging, followed by a torso survey
      and FDG with a torso survey. Images were evaluated qualitatively by an
      experienced observer. RESULTS: Eight patients had pathology-confirmed
      pheochromocytoma. Of the other six, two patients had normal adrenal tissue at
      adrenalectomy, and the other four had subsequent clinical courses inconsistent
      with a diagnosis of pheochromocytoma. In four of eight patients with
      pheochromocytoma, MIBG failed to detect one or more sites of pathology-confirmed
      disease. The mHED-PET detected all sites of confirmed disease, whereas FDG-PET
      detected all sites of adrenal and abdominal disease, but not bone metastases, in
      one patient. MIBG and FDG-PET results were all negative in the six patients
      without pheochromocytoma. One patient with adrenal medullary hyperplasia had a
      positive mHED-PET scan. PET scanning aided the decision not to operate in three
      of six patients. The resolution of PET functional imaging was superior to that of
      MIBG. CONCLUSIONS: PET scanning for pheochromocytoma offers improved quality and
      resolution over current diagnostic approaches. PET may significantly influence
      the clinical management of patients with a suspicion of these tumors and warrants
      further investigation.

PMID- 16418884
TI  - The influence of biologic factors on the surgical decision in advanced
      neuroblastoma.
AB  - BACKGROUND: Molecular markers greatly affect the outcome of neuroblastoma. This
      study evaluated the influence of Trk-A and myelocytomatosis viral-related
      oncogene, neuroblastoma-derived (MYCN) on the role of surgery in advanced
      neuroblastoma. METHODS: Ten stage 3 and 35 stage 4 neuroblastoma patients were
      included. Tumor resection was classified into gross total resection (GTR) and
      incomplete resection. Patients were classified into three biological risk groups
      according to Trk-A expression and myelocytomatosis viral-related oncogene,
      neuroblastoma-derived (MYCN) status in tumor tissues studied by
      immunohistochemistry and fluorescence in situ hybridization, respectively: low
      risk (positive Trk-A and normal MYCN), intermediate risk (negative Trk-A and
      normal MYCN), and high risk (positive or negative Trk-A and MYCN amplification).
      The effect of tumor resection on prognosis was studied and stratified according
      to the risk grouping. RESULTS: GTR was achieved in 21 patients (46.7%) with a
      higher complication rate (33% vs. 8% in the incomplete resection group, P =
      .036). GTR was easier to achieve in low-risk tumors than in intermediate- or high
      risk tumors (12 of 13, 4 of 17, and 5 of 15, respectively; P < .001). GTR
      predicted a favorable prognosis for intermediate-risk patients (P = .037; log
      rank test), but not for low- or high-risk patients because of the overall
      favorable and poor prognosis, respectively. CONCLUSIONS: GTR carries a
      potentially higher possibility of complication. Although GTR can be achieved
      easily in low-risk neuroblastoma patients with a favorable prognosis, surgeons
      should do their best to achieve GTR for intermediate-risk patients to improve
      outcome. Nevertheless, sacrificing vital organs to achieve GTR for high-risk
      patients is not justified.

PMID- 16418885
TI  - American Joint Committee on Cancer clinical stage as a selection criterion for
      sentinel lymph node biopsy in thin melanoma.
AB  - BACKGROUND: A significant proportion of newly diagnosed melanomas are thin
      lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for
      nodal metastases, sentinel lymph node (SLN) biopsy in this subset is
      controversial. Incorporating other prognostic factors (Clark level and
      ulceration), we evaluated the 6th edition American Joint Committee on Cancer
      (AJCC) clinical stage as a simple and widely applicable guideline for offering
      SLN biopsy for thin melanoma. METHODS: This study was a review of a prospective
      melanoma SLN database from 1993 to 2003 with emphasis on SLN positivity rates
      based on the 6th edition AJCC primary tumor thickness intervals and clinical
      stage. RESULTS: Three hundred five patients underwent SLN biopsy, with an overall
      positivity rate of 17.7%. By the 6th edition AJCC, lesions < or = 1.00 mm had an
      SLN positivity rate of 6.6%. By 6th edition clinical stage, SLN positivity rates
      were 4.9% for stage IA and 10.4% for stage IB. By using stage IA as the criterion
      for not offering SLN biopsy, this procedure would have been avoided in 46% (39 of
      85) of < or = 1.00-mm melanoma patients with a negative SLN. CONCLUSIONS: Sixth
      edition AJCC clinical stage IB as a selection criterion for performing SLN biopsy
      in thin melanoma identifies most patients with a positive SLN while also avoiding
      a negative SLN biopsy in many patients. Until additional widely accepted and
      validated selection criteria are available, SLN biopsy for clinical stage IB, but
      not stage IA, thin melanomas is a reasonable approach.

PMID- 16418886
TI  - Hepatic intra-arterial chemotherapy.

PMID- 16418888
TI  - Systemic chemotherapy should be the primary treatment of synchronous colorectal
      metastases in the asymptomatic patient [corrected].

PMID- 16418887
TI  - Induction cisplatin and paclitaxel followed by combination chemoradiotherapy with
      5-fluorouracil, cisplatin, and paclitaxel before resection in localized
      esophageal cancer: a phase II report.
AB  - BACKGROUND: Multimodality therapy for esophageal cancer holds promise for
      improving outcome in this lethal disease. On the basis of encouraging data from a
      phase I trial, we conducted a phase II study of preoperative chemotherapy,
      followed by concurrent chemoradiotherapy and surgery. METHODS: Patients with
      clinically staged resectable esophageal cancer were treated with induction
      cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with
      concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to
      eight weeks after multimodality induction, esophagectomy was performed in
      suitable patients. Study end points were survival, pathologic complete response,
      and toxicity. RESULTS: Twenty-one patients were enrolled with a median age of 58
      years, and all patients were clinically staged II or III. Sixteen (76.2%)
      patients completed the trial, of whom four (25%) had a pathologic complete
      response. One patient died from postoperative complications. Grade 3 or 4
      toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in
      6 of the first 14 patients, thus necessitating a planned dose reduction of
      paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2
      year disease-specific survival for the study population was 78%. CONCLUSIONS:
      This regimen of multimodality therapy before resection resulted in an encouraging
      2-year survival rate but a disappointing rate of pathologic complete response and
      was toxic, necessitating a predetermined paclitaxel dose reduction. The
      incorporation of taxanes into induction strategies for esophageal cancer seems
      promising, but the optimal schedule remains undefined.

PMID- 16418889
TI  - Cypermethrin toxicity to aquatic life: bioassays for the freshwater prawn
      Palaemonetes argentinus.
AB  - Cypermethrin (CY) effects were evaluated in freshwater prawn Palaemonetes
      argentinus, a common member of the aquatic fauna in the vegetated littoral of
      lotic and lentic environment of La Plata basin. LC50 was calculated, and oxygen
      uptakes together with ammonia-N excretion were related to biocide concentrations.
      Behavioral and growth changes were analyzed, and a unique application of CY was
      evaluated in P. argentinus micropopulations. LC50 and their 95% confidence limit
      were 0.0031 microg CY L(-1) (0.0023-0.0039) for 24 h and 0.0020 microg CY L(-1)
      (0.0014-0.0027) for 96 h. Oxygen uptake and ammonia-N excretion increased in the
      prawns kept in CY solutions. The behavioral effect was hyperactivity. Although
      prawns in biocide groups have null or negative growth, the intermolt period was
      246% larger than in the control group. Moreover, the mortality in the second
      cycle was 100%. A unique application of pyrethoid provoked high mortality after
      50 days. The low concentrations of this biocide affected the survival and altered
      the prawn metabolic activity, behavioral and ecdysis cycle. These results suggest
      that juveniles of P. argentinus are much more sensitive to CY pollution than
      other crustaceans, fish, and tadpoles.

PMID- 16418890
TI  - Phenolic acids as bioindicators of fly ash deposit revegetation.
AB  - The floristic composition, the abundance, and the cover of pioneer plant species
      of spontaneously formed plant communities and the content of total phenolics and
      phenolic acids, as humus constituents, of an ash deposit after 7 years of
      recultivation were studied. The restoration of both the soil and the vegetation
      on the ash deposits of the "Nikola Tesla-A" thermoelectric power plant in
      Obrenovac (Serbia) is an extremely slow process. Unfavorable physical and
      chemical characteristics, the toxicity of fly ash, and extreme microclimatic
      conditions prevented the development of compact plant cover. The abundance and
      cover of plants increased from the central part of the deposit towards its edges
      (ranging from 1-80%). Festuca rubra L., Crepis setosa Hall., Erigeron canadensis
      L., Cirsium arvense (L.) Scop., Calamagrostis epigeios (L.) Roth., and Tamarix
      gallica L. were the most abundant species, thus giving the highest cover. Humus
      generated during the decomposition process of plant remains represents a
      completely new product absent in the ash as the starting material. The amount of
      total phenolics and phenolic acids (38.07-185.16 microg/g of total phenolics and
      4.12-27.28 microg/g of phenolic acids) in fly ash increased from the center of
      the deposit towards its edges in correlation with the increase in plant abundance
      and cover. Ash samples contained high amounts of ferulic, vanillic, and p
      coumaric acid, while the content of both p-hydroxybenzoic and syringic acid was
      relatively low. The presence of phenolic acids indicates the ongoing process of
      humus formation in the ash, in which the most abundant pioneer plants of
      spontaneously formed plant communities play the main role. Phenolic compounds can
      serve as reliable bioindicators in an assessment of the success of the
      recultivation process of thermoelectric power plants' ash deposits.

PMID- 16418891
TI  - Evaluation of aquatic toxicities of chromium and chromium-containing effluents in
      reference to chromium electroplating industries.
AB  - This study evaluated aquatic toxicities of chromium and chromium-containing
      laboratory samples representative of effluents from chromium electroplating
      industries, and compared the aquatic environmental risks of hexavalent and
      trivalent chromium electroplating operations. Trivalent chromium electroplating
      has emerged as an acceptable alternative to hazardous hexavalent chromium
      electroplating. This process substitution has reduced the human health impact in
      the workplace and minimized the production of hazardous sludge regulated under
      the Resource Conservation and Recovery Act (RCRA). The thrust behind this
      research was to investigate whether trivalent chromium electroplating operations
      have lower adverse impacts on standardized toxicity test organisms. Ceriodaphnia
      dubia and Pimephales promelas were used to investigate toxicities of trivalent
      chromium (Cr (III)), hexavalent chromium (Cr (VI)), and industrial effluents. In
      agreement with previous studies, Cr (III) was found to be less toxic than Cr
      (VI). Despite having several organic and inorganic constituents in the effluents
      obtained from trivalent chromium plating baths, they exhibited less adverse
      effects to C. dubia than effluents obtained from hexavalent chromium
      electroplating baths. Thus, transition from hexavalent to trivalent chromium
      electroplating processes may be justified. However, because of the presence of
      organic constituents such as formate, oxalate, and triethylene glycol in
      effluents, trivalent chromium electroplating operations may face additional
      regulatory requirements for removal of total organic carbon.

PMID- 16418892
TI  - Organochlorine and heavy-metal contaminants in wild mammals and birds of Urbino
      Pesaro Province, Italy: an analytic overview for potential bioindicators.
AB  - Tissue samples from 56 bird and 11 mammal species of different trophic levels,
      collected from 1994 to 1995 from the Urbino-Pesaro area in the Marche region of
      central Italy, were analyzed for the presence of organochlorine compounds
      (polychlorinated biphenyls and p,p'-DDE) and heavy metals (Pb, Cd, Cr, and Hg).
      Results revealed interspecies differences in pollutant residue concentrations. A
      clear relationship between contaminant and trophic levels emerged depending on
      several factors specific to the chemicals and the organisms, the importance of
      dietary accumulation, and metabolic capacity as it increased toward higher
      trophic levels. Polychlorinated biphenyls and p,p'-DDE were found in all of the
      bird and mammal species analyzed (bird- or fish-eating birds), and insectivore
      mammals showed the highest level of these contaminants. Pb and Hg residues were
      also widely detected and reflected trophic-level differences. The highest
      concentration of Pb was found in herbivorous or bird-eating aquatic invertebrates
      and in insectivorous mammals, particularly in the hedgehog (Erinaceus europaeus),
      whereas the highest Hg levels were found in fish-eating birds. All of the other
      heavy metals were detected at low concentrations and represented background
      levels for birds and mammals, with the exception of increased amounts of Cd and
      Cr, respectively, found in stone marten (Martes foina) and fox (Vulpes vulpes).
      Data from this study provided information on baseline levels of interest to
      monitor status and trends in chemical residue in biota in this specific area, and
      therefore they represent a tool to evaluate potential ecologic, wildlife, and
      human health exposure.

PMID- 16418893
TI  - Synthetic pyrethroid cypermethrin induced cellular damage in reproductive tissues
      of Drosophila melanogaster: Hsp70 as a marker of cellular damage.
AB  - We tested a working hypothesis of whether the synthetic pyrethroid cypermethrin,
      used worldwide for insecticidal purpose, causes adverse effects on reproduction
      in Drosophila melanogaster. Freshly eclosed first instar larvae of a transgenic
      strain of Drosophila melanogaster, Bg9, transgenic for hsp70 (hsp70-lacZ), were
      transferred to different dietary concentrations of the test chemical (0.002,
      0.02, 0.2, 0.5, and 50.0 ppm). Larval mortality was observed at the higher dosed
      groups (0.2, 0.5, and 50.0 ppm). Following pair mating of virgin flies emerging
      from the treatment groups, a significant (p<0.05) effect on reproduction was
      observed in the lowest two dietary concentrations of the test chemical as
      compared to control. The test chemical exhibited a hazardous effect on the
      reproductive organs of the exposed organism as evident by Hsp70 expression and
      tissue damage. The impact of damage was comparatively more prominent in male
      flies than in females. Hsp70 expression was restricted only within the testis
      lobes of male, while ovary in the female fly did not exhibit any Hsp70
      expression. Interestingly, the accessory glands of male flies in these treatment
      groups reflected intense tissue damage as evident by Trypan Blue staining. This
      was further corroborated by ultrastructural changes like higher vacuolization and
      disorganized filamentous bodies in the accessory glands of these groups. The
      present study indicates a profound effect on reproduction by cypermethrin and
      suggests the protective role of hsp70.

PMID- 16418894
TI  - In ovo exposure to a triazine herbicide: effects of atrazine on circulating
      reproductive hormones and gonadal histology in young Japanese quail.
AB  - The triazine herbicide, atrazine, has come under scrutiny for its reported
      feminizing effects in amphibians. To date, there is little information concerning
      the effects of atrazine on reproduction in avian species. The current study
      examined the putative reproductive toxicity of atrazine after exposure in ovo.
      Atrazine at 504, 246, and 123 microg/kg was administered to Japanese quail eggs
      before incubation. The eggs were hatched and the birds raised to 14 days of age.
      Indices of hatchability, sex ratios, and growth were determined. Furthermore,
      circulating concentrations of reproductive hormones (estradiol, progesterone, and
      testosterone) and gonadal histology were examined. Atrazine at 504 microg/kg
      decreased 14-day hatchling weight by 13.1% versus controls. However, no
      detrimental effects on hatchability or sex ratios were observed. In female birds,
      atrazine at 504 microg/kg decreased ovarian weights and circulating
      concentrations of progesterone to 48.3% and 73.3%, respectively, versus control.
      However, concentrations of estradiol and testosterone did not differ from
      controls. In male quail, at all doses tested, atrazine had no effect on gonadal
      weights or circulating concentrations of estradiol, testosterone, or
      progesterone. Moreover, no incidences of left ovotestis formation were observed.
      In contrast, 10 ng/kg ethinylestradiol (a positive control) induced the formation
      of a left ovotestis in four of eight birds analyzed. The current results may
      suggest that exposure to atrazine in ovo at concentrations above ecologic
      relevance exerts effects on the reproductive system of young Japanese quail.
      However, no evidence is presented that atrazine induces feminization of the
      testis in male quail.

PMID- 16418895
TI  - Toxic effects of brominated indoles and phenols on zebrafish embryos.
AB  - Organobromine compounds in the marine environment have been the focus of growing
      attention in past years. In contrast to anthropogenic brominated flame
      retardants, other brominated compounds are produced naturally, e.g., by common
      polychaete worms and algae. Brominated phenols and indoles assumed to be of
      biogenic origin have been detected in water and sediment extracts from the German
      Bight. These substances as well as some of their isomers have been tested with
      the zebrafish embryo test and were found to cause lethal as well as nonlethal
      malformations. The zebrafish test was able to detect a log K(OW)-related toxicity
      for bromophenols, suggesting nonpolar narcosis as a major mode of action.
      Different effect patterns could be observed for brominated indoles and
      bromophenols. The comparison of effective concentrations in the zebrafish embryo
      test with the concentrations determined in water samples suggests the possibility
      that brominated indoles may affect early life stages of marine fish species in
      the North Sea.

PMID- 16418896
TI  - Lipid peroxidation in cadmium-treated Phaseolus coccineus plants.
AB  - Lipid peroxidation was examined in Phaseolus coccineus plants treated with 25
      microM Cadmium (Cd) for 12 days at two different growth stages of the primary
      leaves. In the leaves of Cd-treated young plants, the content of free fatty acids
      was higher only after 8 days of plant exposure to the metal, lipoxygenase
      activity at pH 7.0 was enhanced after 6 and 8 days of Cd action, but at pH 8.0 it
      was higher than control, especially after 8 days. Non-enzymatic lipid
      peroxidation was higher after 6 days of young plant exposure to the metal, but
      after 8 days it slightly decreased. Glutathione-S-transferase activity decreased
      during 12 days of the metal action but it was always higher than in control.
      Anthocyanin content in these plants was also elevated in comparison with control.
      In Cd-treated older plants, the level of free fatty acids was always higher as
      compared to control. Lipoxygenase activity at pH 7.0 was lower after 4 days of
      plant exposure to the metal, but then it was close to control. The enzyme
      activity at pH 8.0 and the level of lipid peroxidation were lower during 12 days
      of Cd action in comparison with control. Glutathione-S-transferase activity and
      anthocyanin pigment content were higher in older Cd-treated plants than in
      control. Relationships between the pool of free fatty acids, a low level of lipid
      peroxidation, and glutathione-S-transferase activity in the primary leaves of Cd
      treated Phaseolus coccineus plants are discussed. In these plants, lipid
      peroxidation is under the strict control of metabolism and the antioxidative
      system works efficiently.

PMID- 16418897
TI  - Bioaccumulation of naturally occurring mixed halogenated dimethylbipyrroles in
      whale and dolphin products on the Japanese market.
AB  - Mixed halogenated dimethyl bipyrroles (HDBPs), which are thought to be produced
      naturally, were quantified in whale and dolphin products marketed for human
      consumption in Japan. The major component of HDBPs was 3,3',4,4'-tetrabromo-5,5'
      dichloro-1,1'-dimethyl -2,2'-bipyrrole (Br(4)Cl(2)-DBP), accounting for 85% of
      the total of five HDBPs detected, followed by Br(3)Cl(2)-DBP. Mean concentrations
      of HDBPs ranged from 0.27 microg/g lipid (n = 31) in minke whale (Balaenoptera
      acutorostrata) from the northwest Pacific Ocean to 11.8 microg/g lipid (n = 33)
      in bottlenose dolphin (Tursiops trucatus) from the southwest Japanese coastal
      water. At higher levels, HDBPs made up 37% of the total organohalogen body burden
      in Dall's porpoise (Phocoenoides dalli), whereas the contribution was less than
      8.9% in minke whales. In two data subsets from Baird's beaked whale (Berardius
      bairdii), the products from the Pacific Ocean contained significantly higher
      concentrations of HDBPs than those from the Sea of Japan. Furthermore, the
      geographical distribution of HDBPs did not resemble those of ubiquitous
      anthropogenic organochlorines, such as polychlorinated biphenyl (PCBs). Higher
      concentration ratios of SigmaHDBP/SigmaPCB and different patterns of HDBP
      congeners were observed in whale products from the Asia-Pacific as compared to
      non-Pacific Ocean mammals reported previously. These results support the
      hypothesis that HDBPs and anthropogenic organochlorines have different sources
      and that the consumption of HDBPs by Japanese individuals could be an
      exposure/health risk.

PMID- 16418898
TI  - Assessment of effects in mink caused by consumption of carp collected from the
      Saginaw River, Michigan, USA.
AB  - Polychlorinated hydrocarbons, including polychlorinated biphenyls (PCBs),
      polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans
      (PCDFs), are ubiquitous environmental contaminants that bioconcentrate in the
      food chain. Numerous studies have demonstrated mink (Mustela vison) to be one of
      the most sensitive species to this group of compounds. In recent studies, a
      lesion characterized by osteoinvasion of epithelial cells into the mandible and
      maxilla of young mink fed diets containing 3,3',4,4',5-pentachlorobiphenyl (PCB
      126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was observed. The objective
      of the present study was to determine if proliferation of maxillary and
      mandibular squamous epithelia could be induced in ranch mink exposed to
      environmentally-derived polychlorinated hydrocarbons (PCBs, PCDDs, and PCDFs) in
      utero, during lactation, and throughout the growth period. Adult female mink were
      fed diets containing 0, 10, 20, or 30% carp (Cyprinus carpio) collected from the
      Saginaw River, Bay City, Michigan, USA, that provided 0.03, 0.83, 1.1, and 1.7 mg
      total PCBs (tPCBs)/kg feed and 2.5, 28, 47, and 73 ng TCDD toxic equivalents
      (TEQs)/kg feed, respectively, three weeks prior to breeding through weaning of
      the resulting offspring. Mink kits were maintained on their respective diets for
      up to 27 weeks of age. At 6 and 27 weeks of age, six to eight mink in each
      treatment group were necropsied and their jaws examined for evidence of maxillary
      and mandibular squamous epithelial proliferation. Results indicated that
      inclusion of up to 30% carp in the diet (1.7 mg tPCBs/kg feed, 73 ng TEQs/kg
      feed) had no effect on mink reproduction and kit survivability. However,
      maxillary and mandibular squamous epithelial proliferation was evident in four of
      the seven 27-week-old juveniles in the 20% carp group (1.1 mg tPCBs/kg feed, 47
      ng TEQs/kg feed) and six of the eight juveniles in the 30% carp group (1.7 mg
      tPCBs/kg feed group, 73 ng TEQs/kg feed). Hepatic concentrations of tPCBs and
      TEQs increased in both the 6-week-old kits and the 27-week-old juveniles as the
      percentage of dietary carp increased. The livers of 6-week-old kits were also
      assessed for the presence of polybrominated diphenyl ethers, which increased as
      the percentage of Saginaw River carp in the diet increased.

PMID- 16418899
TI  - Individual and joint actions of selenate and methylmercury on the development and
      survival of insect detritivore Megaselia scalaris (Diptera: Phoridae).
AB  - Despite the important roles played by insects in most ecosystems, surprisingly
      little is known about how anthropogenic pollutants or their mixtures interact to
      affect insect populations. The independent and joint actions of selenate and
      methylmercury on a ubiquitous insect detritivore, Megaselia scalaris (Loew), were
      determined in this study. Ovipositing females did not distinguish between
      untreated food sources and those contaminated with toxic concentrations of
      selenate, methylmercury, or both chemicals in combination. Even at the highest
      concentrations of pollutants, no negative effects were observed for the egg
      stage. However, larval survival was significantly decreased and development
      significantly prolonged by selenate and methylmercury individually at low or
      intermediate ecologically relevant treatment levels. Potentiation was strongly
      evident because mixtures containing concentrations as little as only 1% of the
      respective individual median lethal tolerances (LC(50)s) caused significantly
      more mortality and delayed larval development than would be expected from the
      responses selenate and methylmercury elicit individually. However, survival and
      pupal development was not affected at any rate tested. Female fecundity was
      significantly decreased by methylmercury but not by selenate or mixture
      treatments. The relative toxicity to M. scalaris of each of the individual and
      joint treatments was selenate (LC(50) = 260 microg/g) < methylmercury (LC(50) =
      22 microg/g) < the mixture at approximately 5% of the LC(50) concentration of
      each of the components (12 microg/g selenate plus 1.0 microg/g methylmercury).
      The increased mortality and delayed larval development within sites contaminated
      by selenate, methylmercury, or combination of the two have substantial
      implications for the ecology, population dynamics, and sustainability of M.
      scalaris populations. If these results can be extrapolated to other arthropod
      detritivores, ecosystem food-web function may be substantially affected.

PMID- 16418900
TI  - Embolization of middle hemorrhoidal artery in the management of life-threatening
      rectal bleeding.

PMID- 16418901
TI  - Use of flyash and biogas slurry for improving wheat yield and physical properties
      of soil.
AB  - This study explores the potential use of by-products of energy production, i.e.,
      (i) flyash from coal-powered electricity generation and (ii) biogas slurry from
      agricultural waste treatment, as nutrient sources in agriculture. These residues
      are available in large amounts and their disposal is a major concern for the
      environment. As both residues contain considerable amounts of plant nutrients,
      their use as soil amendment may offer a promising win-win opportunity to improve
      crop production and, at the same time, preventing adverse environmental impacts
      of waste disposal. Effect of flyash and biogas slurry on soil physical properties
      and growth and yield of wheat (Triticum aestivum) was studied in a field
      experiment. Leaf area index, root length density and grain yield of wheat were
      higher in plots amended with flyash or biogas slurry compared to unamended plots.
      Both types of amendments reduced bulk density, and increased saturated hydraulic
      conductivity and moisture retention capacity of soil. The study showed that
      flyash and biogas slurry should be used as soil amendments for obtaining short
      term and long-term benefits in terms of production increments and soil
      amelioration.

PMID- 16418902
TI  - Assessing the effects of non-point source pollution on American Samoa's coral
      reef communities.
AB  - Surveys were completed on Tutuila Island, American Samoa, to characterize reef
      development and assess the impacts of non-point source pollution on adjacent
      coral reefs at six sites. Multivariate analyses of benthic and coral community
      data found similar modern reef development at three locations; Aoa, Alofau, and
      Leone. These sites are situated in isolated bays with gentle sloping foundations.
      Aoa reefs had the highest estimates of crustose coralline algae cover and coral
      species richness, while Leone and Alofau showed high abundances of macroalgae and
      Porites corals. Aoa has the largest reef flat between watershed discharge and the
      reef slope, and the lowest human population density. Masefau and Fagaalu have a
      different geomorphology consisting of cemented staghorn coral fragments and steep
      slopes, however, benthic and coral communities were not similar. Benthic data
      suggest Fagaalu is heavily impacted compared with all other sites. Reef
      communities were assessed as bio-criteria indicators for waterbody health, using
      the EPA aquatic life use support designations of (1) fully supportive, (2)
      partially supportive, and (3) non-supportive for aquatic life. All sites resulted
      in a partially supportive ranking except Fagaalu, which was non-supportive. The
      results of this rapid assessment based upon relative benthic community measures
      are less desirable than long-term dataset analyses from monitoring programs,
      however it fills an important role for regulatory agencies required to report
      annual waterbody assessments. Future monitoring sites should be established to
      increase the number of replicates within each geological and physical setting to
      allow for meaningful comparisons along a gradient of hypothesized pollution
      levels.

PMID- 16418903
TI  - Linking land cover and water quality in New York City's water supply watersheds.
AB  - The Catskill/Delaware reservoirs supply 90% of New York City's drinking water.
      The City has implemented a series of watershed protection measures, including
      land acquisition, aimed at preserving water quality in the Catskill/Delaware
      watersheds. The objective of this study was to examine how relationships between
      landscape and surface water measurements change between years. Thirty-two
      drainage areas delineated from surface water sample points (total nitrogen, total
      phosphorus, and fecal coliform bacteria concentrations) were used in step-wise
      regression analyses to test landscape and surface-water quality relationships.
      Two measurements of land use, percent agriculture and percent urban development,
      were positively related to water quality and consistently present in all
      regression models. Together these two land uses explained 25 to 75% of the
      regression model variation. However, the contribution of agriculture to water
      quality condition showed a decreasing trend with time as overall agricultural
      land cover decreased. Results from this study demonstrate that relationships
      between land cover and surface water concentrations of total nitrogen, total
      phosphorus, and fecal coliform bacteria counts over a large area can be evaluated
      using a relatively simple geographic information system method. Land managers may
      find this method useful for targeting resources in relation to a particular water
      quality concern, focusing best management efforts, and maximizing benefits to
      water quality with minimal costs.

PMID- 16418904
TI  - Field evaluation of mixing length and attenuation of nutrients and fecal coliform
      in a wastewater effluent plume.
AB  - We present an alternative method to dye tracer studies for mapping wastewater
      effluent plumes in rivers. A case study of a wastewater treatment effluent plume
      that was mapped in two different months (October and April) showed good
      resolution in determining where the plume reached the opposite river bank, the
      degree of mixing in a given river reach, and where the river was fully mixed with
      respect to the plume. Both electrical conductivity and chloride were useful in
      mapping domestic wastewater effluent plume mixing. Mixing lengths obtained by
      field mapping were consistent with previous studies. Electrical conductivity
      field readings facilitated real-time plume delineation and sampling locations,
      and identified a non-point source plume during the mapping exercise. The apparent
      difference in dispersion of the plume between to the two mapping dates (despite
      similar upstream river discharge) suggests that the calibration of a water
      quality model based on a single dye test may be inadequate. The river
      distributions of effluent nutrients and fecal coliform were also mapped. Nutrient
      attenuation rates were faster than that of the chloride tracer, indicating
      processes other than mixing occur. Substantial differences were observed in
      nutrient and fecal coliform distributions between the two mapping dates.

PMID- 16418905
TI  - Developing a national indicator of soil quality on U.S forestlands: methods and
      initial results.
AB  - The Montreal Process was formed in 1994 to develop an internationally agreed upon
      set of criteria and indicators for the conservation and sustainable management of
      temperate and boreal forests. In response to this initiative, the Forest
      Inventory and Analysis (FIA) and Forest Health Monitoring (FHM) programs of the
      United States Department of Agriculture Forest Service have implemented soil
      measurements as part of a national monitoring program to address specific
      questions related to the conservation of soil and water resources. Integration of
      soil assessments into the national FIA program provides for systematic monitoring
      of soil properties across all forested regions of the U.S. using standardized
      collection, laboratory, and statistical procedures that are compatible with
      existing forest inventory data. The resulting information will provide
      quantitative benchmarks for regional, national, and international reporting on
      sustainable forest management and enhance our understanding of management effects
      on soil quality. This paper presents an overview of the FIA soil monitoring
      program, outlines the field and laboratory protocols as currently implemented,
      and provides examples of how these data may be used to assess indicators of
      sustainable management as defined by the Montreal Process.

PMID- 16418906
TI  - Sources and concentrations of mercury and selenium in compartments within the Las
      Vegas Wash during a period of rapid change.
AB  - The Las Vegas Wash, which drains the Las Vegas valley watershed and provides the
      second largest inflow to Lake Mead, is being dramatically altered with erosion
      control structures and wetland restoration efforts. The impact of these changes
      on the cycling and distribution of Hg and Se is of particular interest because of
      their tendency to bioaccumulate and because of a lack of information on these
      contaminants in the Wash. In this study, we determined concentrations of Hg and
      Se in surface water (monthly), groundwater (once) and sediments (quarterly) from
      strategic locations within and along the Wash during 2002 and 2003. The data was
      used to characterize Se sources and loading into the Wash. Samples containing
      resurfacing groundwater and urban runoff (LW10.75 and Duck Creek) had
      significantly higher yearly means (13.7 +/- 4.4 and 23.8 +/- 4.1 microg/L,
      respectively) compared with mainstream samples containing primarily treated
      wastewater (2.8 +/- 0.8 microg/L). Investigation of Se in tributaries, street
      runoff and rain suggest that the source of the elevated Se is likely groundwater
      seeps located within a relatively narrow geographic band on the southeast side of
      the valley. Se content of sediments was similar, except for LW10.75 which was
      rich in organic matter. Hg concentrations in the water and sediments were low,
      averaging 4 +/- 5 ng/L and 34 +/- 20 ng/g, dw, respectively. Overall, this study
      suggests that water quality remains relatively stable despite changes in the Wash
      and managers of developing wetlands should not use tributary water as source
      water.

PMID- 16418907
TI  - Biomonitoring of lead in atmospheric environment of an urban center of the Ganga
      Plain, India.
AB  - Monitoring of atmospheric lead from the Dalbergia sissoo tree was undertaken at
      Lucknow urban centre of the Ganga Plain, India. A total of 26 leaf samples were
      collected in spring, monsoon and winter seasons from 16 sampling sites and was
      analysed by Atomic Absorption Spectrophotometry method. Lead concentrations were
      low in spring season, increased in monsoon to winter seasons and range from 2.1
      to 28.2 microg/g (dry wt.). This accumulative response of lead in the tree leaves
      is directly linked with the exposure time of automobile emission that is
      considered to be the predominant source for it. Highway localities show higher
      lead concentrations by a factor of 2 as compared to urban localities. Highest
      concentration was recorded at Sitapur Road (National Highway No. 24) in winter
      season. A linear quantitative relationship between urban air-lead levels and lead
      in-the Dalbergia sissoo leaves is used to infer the qualitative assessment of
      present day atmospheric lead pollution. Reported results suggest a drastic
      reduction in mean lead concentration in Lucknow urban air from 1.32 microg/m3 in
      1994 to 0.19 microg/m3 in 2002. Similarly, mean lead concentration in the tree
      leaves during winter season also dropped from 17.9 microg/g in 1994 to 8.1
      microg/g in 2004. Despite of increasing urban population, urban area, vehicle
      population and traffic density, the introduction of unleaded-petrol (vehicular
      fuel) keeps lead level in the urban environment of Lucknow much lower than the
      past. Like Lucknow, other urban centres of the Ganga Plain are also on way to the
      exponential increase in pressure of urbanization. An appropriate urban public
      transport planning is required to provide healthy atmospheric environment for
      millions of people especially future young generation.

PMID- 16418908
TI  - Distribution of iron, manganese, zinc and atrazine in groundwater in parts of
      Palar and Cheyyar river basins, South India.
AB  - A study was carried out in a part of Palar and Cheyyar river basin to evaluate
      the current status of iron, manganese, zinc and atrazine concentrations, their
      origin and distribution in groundwater. Groundwater samples were collected during
      post-monsoon (March 1998 and February 1999) and pre-monsoon (June 1999) periods
      from 41 sampling wells distributed throughout the study area. The groundwater
      samples were analyzed for trace metals using AAS and atrazine using HPLC. The
      concentration of the trace elements in groundwater is predominant during pre
      monsoon period. Distribution pattern indicates that the concentration of these
      elements increases from west to northeast and towards Palar river. Lower
      concentrations in the central part may be due to recharge of fresh water from the
      lakes located here. During most of the months, as there is no flow in Palar
      river, the concentrations of trace elements in groundwater are high. Drinking
      water standards indicate that Mn and Zn cross the permissible limit recommended
      by EPA during the pre-monsoon period. A comparison of groundwater data with trace
      element chemistry of rock samples shows the abundance of trace elements both in
      the rock and water in the order of Fe > Mn > Zn and Fe > Zn > Mn. This indicates
      that iron in groundwater is derived from lithogenic origin. Further, Fe, Mn and
      Zn have good correlation in rock samples, while it is reverse in the case of
      water samples, indicating the non-lithogenic origin of Mn and Zn. Atrazine (a
      herbicide) was not detected in any of the groundwater samples in the study area,
      perhaps due to low-application rate and adsorption in the soil materials.

PMID- 16418909
TI  - Biotransformation and genotoxic biomarkers in mullet species (Liza sp.) from a
      contaminated coastal lagoon (Ria de Aveiro, Portugal).
AB  - The aim of the present study was to assess liver ethoxyresorufin-O-deethylase
      (EROD) activity and erythrocytic nuclear abnormalities (ENA) frequency in three
      mullet species, as biotransformation and genotoxicity biomarkers, respectively,
      for monitoring aquatic ecosystems. Specimens of Liza aurata, Liza ramada and Liza
      saliens were caught bimonthly, between May 2000 and March 2001, at nine stations
      in the Ria de Aveiro (Portugal), a polluted coastal lagoon. The survey revealed
      two critical areas (Vagos and Carregal) where it was observed elevated EROD
      activity and ENA frequency, comparing to the reference sites. The results often
      reflect a contamination by a mixture of pollutants, from point and non-point
      sources. Nevertheless, the responses observed at Vagos are probably attributable
      to high polycyclic aromatic hydrocarbon (PAH) water levels measured at that
      station. All species were able to detect inter-site differences; however L.
      aurata seems to be the most appropriate bio-indicator due to its larger
      geographical distribution and abundance during the whole year. The adopted
      biomarkers, applied to mullet species, can be successfully employed for
      biomonitoring anthropogenic contamination in both Atlantic and Mediterranean
      European coastal waters.

PMID- 16418911
TI  - Persistence and dissipation of readymix formulations of insecticides in/on okra
      fruits.
AB  - Dissipation behaviour of ready mix polytrin C 44EC (profenophos 40% +
      cypermethrin 4%) and spark 36EC (triazophos 35% + deltamethrin 1%) applied at 1
      L/ha in okra crop during Kharif in year 2000 was studied at 0, 1, 3, 5 and 7 days
      after treatment. Dissipation on 7th day was found to be maximum (98.4%) for
      profenophos followed by triazophos (86.2%), cypermethrin (73.5%) and deltamethrin
      (55.7%). Half life (t1/2) values for the above insecticides were 1.35, 2.55, 4.11
      and 7.60 days, respectively. All the insecticides followed a first order
      kinetics. Profenophos and triazophos followed a biphasic dissipation pattern with
      faster dissipation in phase I (0-1 days) and manifesting slower rate of
      dissipation in phase II (1-7 days).

PMID- 16418913
TI  - Artificial sampling units: a tool for increasing the sensitivity of tests for
      impact in soft sediments.
AB  - The distribution of benthic organisms in soft sediments is patchy in time and
      space on many scales. Such variability makes assessment of ecological impacts
      difficult. Sediment-related variables, such as grain-size and organic content,
      which can affect colonization by infauna, vary over similar scales. Variations in
      characteristics of the sediment may contribute to spatial variability in infaunal
      assemblages, making it difficult to detect the putative impacts of disturbances,
      such as the production of boat-generated waves (wash), on these organisms. Here,
      the hypothesis that infaunal assemblages colonizing containers of homogeneous
      sediment would be less spatially variable than those colonizing natural sediment
      was tested. Containers were deployed at mudflats differing in exposure to wash.
      If wash does affect colonization, a reduction in variability among sites of
      similar exposure should enable stronger differences to be seen between wash and
      no-wash zones. Assemblages colonizing homogeneous sediment were less variable
      than those colonizing site-specific sediment. No difference in colonization was,
      however, seen between places differing in their exposure to wash. Nevertheless,
      this method is of use in the assessment of ecological impacts in sedimentary
      environments, where it is difficult to detect putative impacts above the great
      natural variability in assemblages.

PMID- 16418912
TI  - Interpretation and discrimination of marshy wetlands by soil factors in the Kuan
      Tu Natural Park, Taiwan.
AB  - This work investigated soil samples collected from Kuan-Tu wetlands, Taiwan.
      Factor analysis was performed to explain the impact of various soil factors on
      this marshy wetlands located in suburban Taipei. The results indicated that the
      latent factors were heavy metals, salinity, and soil organic matter. Canonical
      discriminant analysis was used to improve an existing vegetation classification
      scheme by identifying the physical-chemical properties of sediment in Kaun-Tu
      wetlands, Taiwan. Predictive discriminant analysis was used to examine the
      ability of the models to predict class membership for unknown soil sample.
      Multivariate analysis of the spatial patterns of soil quality and vegetation
      types showed that different properties of soil grew different types of vegetation
      and absorbed contaminants differently. We can feasibly conserve a suitable
      habitat for wetland biology by processing these unstable predictor variables. The
      methodology and results provide useful information concerning the Kuan-Tu
      wetlands and may be applicable to other wetlands with similar properties that are
      experiencing similar environmental issues.

PMID- 16418910
TI  - Application of a dialysis sampler to monitor phytoremediation processes.
AB  - A cylindrical dialysis sampler (1.2 m in length; 5 cm in diameter) was designed
      and constructed to sample small-scale phytoremediation processes in the root zone
      of poplar trees. The study site was a 183-tree plantation of hybrid poplars
      located at Aberdeen Proving Ground, Maryland, at the J-Field Area of Concern. The
      grove was planted in 1996 to intercept a chlorinated solvent plume containing
      1,1,2,2-tetrachloroethane (1,1,2,2-TeCA, trichloroethene (TCE) and daughter
      products. Two dialysis samplers were installed: one directly in the poplar grove
      (approximately 0.3 m from the trunk of a mature tree) and the other outside of
      the grove but in the plume. Data collected included concentrations of chlorinated
      VOCs, organic acids, chloroacetic acids, Cl-, and dissolved gases (ethane,
      ethene, CH4, CO2). At the control location, the VOC profile was dominated by cis
      1,2-dichloroethene (cis-1,2-DCE) and trans-1,2-dichloroethene (trans-1,2-DCE)
      with concentrations ranging from 0.88-4.5 to 4.4-17.6 mg/L, respectively.
      Concentrations of VOCs were similar across the vertical profile. At the tree
      location, 1,1,2,2-TeCA and TCE were the dominant VOCs detected but as opposed to
      the control location were highly variable within the root zone, with the greatest
      variability associated with locations in the sampler where roots were observed.
      This highly variable profile at the tree location is indicative of VOC
      rhizosphere biodegradation and uptake near the active roots. This variability
      appears to be on the centimeter scale, emphasizing the importance of these high
      resolution samplers for the study of rhizosphere influences.

PMID- 16418914
TI  - Seasonal variation of chemical composition in fine particles at Gosan, Korea.
AB  - PM2.5 aerosol samples were collected at Gosan in Jeju Island during six intensive
      measurement periods between November 2001 and August 2003. In order to
      investigate the chemical composition of fine particles, major ion components,
      trace elements, and elemental and organic carbon were analyzed. Quite different
      seasonal characteristic in the chemical composition of fine particles was
      observed. The concentration of most secondary aerosol components showed a summer
      minimum and a winter maximum with higher correlation between them at Gosan. This
      fact clearly reveals the possibility of long-range transport of such pollutants
      in winter. On the other hand, OC and EC had the highest concentration and good
      correlation with ion components, such as K+, Ca2+ in fall. It means that biomass
      burning could significantly influence the ambient fine carbonaceous particulate
      in fall, which was primarily long-range transported.

PMID- 16418915
TI  - Heavy metals in liver and muscle of bluefin tunA (Thunnus thynnus) caught in the
      Straits of Messina (Sicily, Italy).
AB  - The present investigation was carried out on the bluefin tuna (Thunnus thynnus)
      collected during the month of April 2003 from the Straits of Messina. The aim of
      this study is to determine heavy metal levels (Cd, Cu, Hg, Mn, Pb and Zn) in
      liver and muscle tissues of 14 Thunnus thynnus of different age and sex and to
      investigate the relationships between fish sex and size (length and weight) and
      metal concentrations in the tissues. The concentrations of the various metals
      were determined by a Varian atomic absorption spectroscopy instrument. The
      results show significant variations (p < 0.01) for Hg and Zn concentrations in
      muscle than in liver samples. Concentrations of Cd and Pb are below the
      instrumental detection limits in almost all muscle samples. Levels of Hg (3.03 +/
      0.55 microg/g) are above the MRLs only in muscle (1 microg/g) establishing
      toxicological risks for the consumer. Regression analysis shows a negative
      correlation between mercury level and weight and length in samples from both
      female and male. No significant difference between mean heavy metals
      concentrations and male or female tuna is seen. For greater food safety, it would
      be advisable to reduce the mercury intake by selecting safer fish, species and
      size and by the avoidance of tuna fish consumption by pregnant women, young
      children and old people, who are more sensitive to mercury exposure.

PMID- 16418916
TI  - Development of a quality-assessed agrichemical database for monitoring
      anthropogenic impacts on ground-water quality.
AB  - The Quality-Assessed Agrichemical Contaminant Database for Nebraska Ground Water
      is a unique repository of nitrate and pesticide data collected by federal, state,
      and local agencies. Each contaminant concentration in the database has been
      evaluated based upon well-defined criteria that address completeness of the well
      attribute data, analytical method and field and laboratory quality control
      practices and assigned to one of five quality levels. The quality assessment
      level always accompanies the contaminant concentration so that the end-user knows
      the quality assurance effort expended in the acquisition of the data, can select
      comparable data, and choose data whose quality assurance effort is commensurate
      with project objectives. The database can be viewed and queried on-line;
      downloaded in its entirety; or imported to a spreadsheet or a geographic
      information system. Setting criteria for data quality and assessing the level of
      quality have resulted in significant increases in the percentages of high quality
      (Levels 3-5) nitrate and pesticide data. These high quality data presently
      constitute 52% of the nitrate and 55% of the pesticide data.

PMID- 16418918
TI  - Heavy metals and selenium in grebe eggs from Agassiz National Wildlife Refuge in
      northern Minnesota.
AB  - Metal levels in eggs can often be used as an indicator of exposure and of
      potential effects. In previous work at Agassiz National Wildlife Refuge,
      northwestern Minnesota, the levels of several heavy metals were shown to be
      significantly higher in the eggs of eared grebes (Podiceps nigricollis) compared
      to those in the eggs of Franklin's gulls (Larus pipixcan), black-crowned night
      herons (Nycticorax nycticorax) and double-crested cormorants (Phalacrocorax
      auritus, except for mercury). In the present study we test the hypothesis that
      there are no differences in the levels of heavy metals in eggs of three species
      of grebes nesting at Agassiz National Wildlife Refuge (1997, 1999). There were
      significant differences in levels of selenium, manganese and mercury in the eggs
      of the grebes collected in 1997, with pied-billed grebe (Podilymbus podiceps)
      having significantly higher levels of manganese and mercury, and significantly
      lower levels of selenium, than eared or red-necked grebes (Podiceps grisegena).
      In 1999, pied-billed grebes had significantly higher levels of mercury, but lower
      levels of selenium and tin than the other species. The only pattern that was
      significant and consistent among years was selenium; in both years pied-billed
      grebes had lower levels than the other species. For eared grebes, there was a
      decline from 1997 to 1998, and again to 1999 for arsenic, cadmium, and selenium.
      Levels of mercury in the eggs of grebes were not as high, however, as those found
      in cormorants or night-herons sampled in 1994 at Agassiz National Wildlife
      Refuge. There were few consistent patterns in the relationships among metals in
      eared grebe eggs (with the largest sample sizes). The possible reasons for the
      high levels of some metals in eggs of grebes are unknown, but presumably egg
      levels represent exposure on the wintering grounds or migratory routes. In
      comparison to eggs of other birds: 1) the mean levels for manganese were at the
      high end of the range, and the mean was an order of magnitude higher than the
      median for the studies examined, 2) mean levels were above the median in the eggs
      of other birds for lead (red-necked grebe), mercury (pied-billed grebe) and
      selenium (eared and red-necked grebe).

PMID- 16418919
TI  - Status and trends of dissolved oxygen in Corpus Christi Bay, Texas, U.S.A.
AB  - The purpose of this study was to determine status and long-term trends of
      dissolved oxygen concentrations (DO) in Corpus Christi Bay, Texas, U.S.A. A 20
      year record of randomized stations was used to determine the trend of surface
      water DO, salinity, and temperature over space and time. A 13-year record of two
      fixed stations was used to determine the temporal nutrient trends. A 10-year
      record of fixed stations in the southeastern region of Corpus Christi Bay was
      used to determine the status of disturbance caused by low DO in bottom waters.
      From 1982 to 2002, there was a significant decrease in surface water DO at a rate
      of 0.06 mg L(-1) yr(-1) and a significant increase in surface water temperature
      at a rate of 0.07 degrees C yr(-1). The southeastern region of Corpus Christi Bay
      had the lowest average DO, and during July and August, DO are steadily declining
      at a rate of 0.09 mg L(-1) yr(-1). It is not likely that eutrophication is
      causing hypoxia, because freshwater inflow rates have significantly decreased
      since 1941 and nutrient levels have not changed from 1987 to 2000. Even though
      long-term trends indicate that average surface DO is decreasing, disturbance by
      hypoxia appears to be stable, but this may be due to just eight years of data. In
      fact, if the current trend continues, surface water DO will not meet exceptional
      aquatic life standards (< or = 5 mg L(-1)) in 2032.

PMID- 16418920
TI  - Mineralogy of atmospheric suspended dust in three indoor and one outdoor location
      in Oman.
AB  - The aim of this work is to characterize the mineral phases present in the
      atmosphere at three locations in northern Oman. Samples of atmospheric particles
      were collected using a high volume sampler. Three indoor and one outdoor location
      were chosen in this investigation. Sampling locations included a residential
      house located nearby the cement plant, a residential house located nearby a
      refinery plant, and a residential house located at Al-Suwayq residential area.
      Indoor air was sampled from these three houses. Moreover, for the Al-Suwayq
      residential house, sampling was also taken outside the house for comparison. The
      dust samples were analysed for their microanalysis characterization and their
      mineral contents as well. The microanalysis enabled us to identify the metals
      present in the particles. Furthermore, the mineralogical analysis of the sample
      filters showed the presence of quartz as the principal phase inside the house of
      Al-Suwayq, whereas quartz, dolomite, and gypsum were common phases outside the
      house. In the residential house nearby the cement plant, it was found that
      calcite, quartz, dolomite and goethite were the principal phases whereas the
      particles collected from the house nearby the refinery composed primarily of
      dolomite and calcite. The airborne dust collected at the refinery and Al-Suwayq
      were probably sourced in the natural environment and mobilised by natural
      processes. However, at the cement factory the crushing and grinding of limestone
      during the industrial process has contributed significantly to the airborne dust
      load. Generally, the information obtained in this study will be invaluable as no
      data for the mineral content of atmospheric dust existed in the Oman.

PMID- 16418917
TI  - Arsenic speciation analysis in water samples: a review of the hyphenated
      techniques.
AB  - Interests in the determination of different arsenic species in natural waters is
      caused by the fact that toxic effects of arsenic are connected with its chemical
      forms and oxidation states. In determinations of water samples inorganic arsenate
      (As(III), As(V)), methylated metabolities (MMAA, DMAA) and other organic forms
      such as AsB, AsC, arsenosugars or arsenic containing lipids have the most
      importance. This article provides information about occurrence of the dominant
      arsenic forms in various water environments. The main factors controlling arsenic
      speciation in water are described. The quantification of species is difficult
      because the concentrations of different forms in water samples are relatively low
      compared to the detection limits of the available analytical techniques. Several
      hyphenated methods used in arsenic speciation analysis are described. Specific
      advantages and disadvantages of methods can define their application for a
      particular sample analysis. Insufficient selectivity and sensitivity of arsenic
      speciation methods cause searching for a new or modifications already existing
      techniques. Some aspects of improvement and modifications of the methods are
      highlighted.

PMID- 16418921
TI  - Effect of the carbohydrate composition of feed concentratates on methane emission
      from dairy cows and their slurry.
AB  - Dietary carbohydrate effects on methane emission from cows and their slurry were
      measured on an individual animal basis. Twelve dairy cows were fed three of six
      diets each (n = 6 per diet) of a forage-to-concentrate ratio of 1 : 1 (dry matter
      basis), and designed to cover the cows' requirements. The forages consisted of
      maize and grass silage, and hay. Variations were exclusively accomplished in the
      concentrates which were either rich in lignified or non-lignified fiber, pectin,
      fructan, sugar or starch. To measure methane emission, cows were placed into open
      circuit respiration chambers and slurry was stored for 14 weeks in 60-L barrels
      with slurry being intermittently connected to this system. The enteric and slurry
      organic matter digestibility and degradation was highest when offering Jerusalem
      artichoke tubers rich in fructan, while acid-detergent fiber digestibility and
      degradation were highest in cows and slurries with the soybean hulls diet rich in
      non-lignified fiber. Multiple regression analysis, based on nutrients either
      offered or digested, suggested that, when carbohydrate variation is done in
      concentrate, sugar enhances enteric methanogenesis. The methane emission from the
      slurry accounted for 16.0 to 21.9% of total system methane emission. Despite a
      high individual variation, the methane emission from the slurry showed a trend
      toward lower values, when the diet was characterized by lignified fiber, a diet
      where enteric methane release also had been lowest. The study disproved the
      assumption that a lower enteric methanogenesis, associated with a higher
      excretion of fiber, will inevitably lead to compensatory increases in methane
      emission during slurry storage.

PMID- 16418922
TI  - Influence of environmental factors on the evolution of industrial noise-induced
      hearing loss.
AB  - The aim of the study is to investigate how environmental factors, associated with
      exposure to industrial noise, affect the development of chronic noise-induced
      hearing loss. The study was conducted on 186 male subjects working in two
      bottling plants, situated respectively in a small farming community, and in a
      medium-sized city with significant levels of noise pollution. Levels of
      occupational exposure were the same for the two groups. The subjects were
      selected by means of a preliminary medical examination, and exposed to tonal
      hearing tests and acoustic impedance tests. Statistical analysis was performed on
      hearing threshold values obtained at the frequencies of 500, 1000, 2000 and 4000
      Hz. The comparison between the thresholds obtained in the two groups showed a
      statistically significant difference, especially at the frequency of 4000 Hz and
      for occupational exposure exceeding 17 yr. The results led us to conclude that
      environmental factors, and urban noise in particular, influence the onset and
      development of occupational acoustic trauma, and that those working in the
      country are significantly less affected than those in the city. Since
      occupational exposure was the same for both groups, their different responses
      must therefore be interpreted as due to differences in non-occupational exposure,
      in turn dependent on different opportunities for rest from noise and different
      levels of exposure to noise pollution.

PMID- 16418923
TI  - Variability in VOC concentrations in an urban area of Delhi.
AB  - The variability of pollutants is an important factor in determining human
      exposure to the chemicals. This study presents the result of investigation of
      variability of Volatile organic compounds (VOCs) in urban area of Delhi, capital
      of India. Fifteen locations, in five categories namely residential, commercial,
      industrial, traffic intersections and petrol pump were monitored for one year
      every month during peak hours in morning and evening. Measurement focused on
      target VOCs as defined by USEPA. Variability was divided into measurement,
      spatial, temporal and temporal-spatial interaction components. Temporal component
      along with temporal-spatial interaction were found to be the major contributors
      to the variability of measured VOC concentrations. Need of continuous monitoring
      to capture short-term peak concentration and averages is evident.

PMID- 16418924
TI  - Assessing the response of estuarine intertidal assemblages to urbanised catchment
      discharge.
AB  - Measurement of intertidal rock assemblages was investigated as a potential
      biological indicator to provide a quantitative estimate of the impact of
      urbanised catchment discharge on the estuaries of Sydney, Australia, from 1995 to
      1999. Based on the presence and characteristics of adjacent human activities,
      sampling locations were categorised as: Bush; Urban; Urban with Sewer Overflows;
      and Industry with Sewer Overflows. In Sydney Harbour, variation in assemblage
      structure was measured between most impact categories, however differences
      between impact categories were not consistent for each year. Nevertheless, in
      years of above average rainfall (1998-1999), reference assemblages adjacent to
      national parks and distant from urbanisation were different to all other
      putatively impacted assemblages. Variability within assemblages was least at
      reference locations in each year and greatest at locations adjacent to stormwater
      canals and sewer overflows, particularly in 1998-1999. Variation in assemblage
      structure in Sydney estuaries was most strongly correlated with chlorophyll--a
      concentrations. Univariate analysis also identified highly significant
      differences for a number of factors, however, interactions between year, impact
      categories and location for numerous analyses, confounded the differentiation
      between impact categories. The results suggest that intertidal rock assemblages
      in Sydney Harbour and surrounding estuaries appear to be responding to the
      quality and quantity of discharge from urbanised catchments and, furthermore,
      that assemblages are more suitable than individual taxa to indicate the
      difference between Bush and anthropogenically disturbed estuarine locations.

PMID- 16418925
TI  - Quantification of polycyclic aromatic hydrocarbons in tea and coffee samples of
      Mumbai City (India) by high performance liquid chromatography.
AB  - This paper describes a method for quantification of sixteen polycyclic aromatic
      hydrocarbons (PAHs) in tea and coffee samples of Mumbai City with the help of
      reversed phase high performance liquid chromatography with UV-VIS detector. This
      method is based on liquid-liquid extraction followed by clean up with C-18
      cartridge. Concentration of total PAHs in different brands of tea and coffee
      samples varied from 18.79 to 31.37 microg/L and from 16.47 to 18.24 microg/L,
      respectively. Mean concentration of total PAHs was 27.56 microg/L in tea and
      17.20 microg/L in coffee. Recoveries at different concentration levels were
      higher than 68% in samples of tea and coffee. Detection limit was found to be low
      (0.0006 ng) for anthracene and highest (0.174 ng) for naphthalene with relative
      standard deviation between 0.4%-7%.

PMID- 16418926
TI  - Linking on-farm dairy management practices to storm-flow fecal coliform loading
      for California coastal watersheds.
AB  - How and where to improve water quality within an agricultural watershed requires
      data at a spatial scale that corresponds with individual management decision
      units on an agricultural operation. This is particularly true in the context of
      water quality regulations, such as Total Maximum Daily Loads (TMDLs), that
      identify agriculture as one source of non-point source pollution through larger
      tributary watershed scale and above and below water quality investigations. We
      have conducted a systems approach study of 10 coastal dairies and ranches to
      document fecal coliform concentration and loading to surface waters at the
      management decision unit scale. Water quality samples were collected on a storm
      event basis from loading units that included: manure management systems; gutters;
      storm drains; pastures; and corrals and lots. In addition, in-stream samples were
      collected above and below the dairy facilities and from a control watershed,
      managed for light grazing and without a dairy facility or human residence and
      corresponding septic system. Samples were analyzed for fecal coliform
      concentration by membrane filtration. Instantaneous discharge was measured for
      each collected sample. Storm runoff was also calculated using the curve number
      method (SCS, 1985). Results for a representative dairy as well as the entire 10
      dairy data set are presented. Fecal coliform concentrations demonstrate high
      variability both within and between loading units. Fecal coliform concentrations
      for pastures range from 206 to 2,288,888 cfu/100 ml and for lots from 1,933 to
      166,105,000 cfu/100 ml. Mean concentrations for pastures and lots are 121,298 (SE
      = 62,222) and 3,155,584 (SE = 1,902,713) cfu/100 ml, respectively. Fecal coliform
      load from units of concentrated animals and manure are significantly more than
      units such as pastures while storm flow amounts were significantly less. Compared
      with results from earlier tributary scale studies in the watershed, this systems
      approach has generated water quality data that is beneficial for management
      decisions because of its scale and representation of current management
      activities. These results are facilitating on-farm changes through the
      cooperative efforts of dairy managers, regulatory agency staff, and sources of
      technical and financial assistance.

PMID- 16418927
TI  - Use of satellite imagery as environmental impact assessment tool: a case study
      from the NW Egyptian Red Sea coastal zone.
AB  - Knowledge and detecting impacts of human activities on the coastal ecosystem is
      an essential management requirement and also very important for future and proper
      planning of coastal areas. Moreover, documentation of these impacts can help in
      increasing public awareness about side effects of unsustainable practices.
      Analysis of multidate remote sensing data can be used as an effective tool in
      environmental impact assessment (EIA). Being synoptic and frequent in coverage,
      multidate data from Landsat and other satellites provide a reference record and
      bird's eye viewing to the environmental situation of the coastal ecosystem and
      the associated habitats. Furthermore, integration of satellite data with field
      observations and background information can help in decision if a certain
      activity has caused deterioration to a specific habitat or not. The present paper
      is an attempt to utilize remote sensing data for assessment impacts of some human
      activities on the major sensitive habitats of the NW Egyptian Red Sea coastal
      zone, definitely between Ras Gemsha and Safaga. Through multidate change analysis
      of Landsat data (TM & ETM+ sensors), it was possible to depict some of the human
      infringements in the area and to provide, in some cases, exclusive evidences for
      the damaging effect of some developmental activities.

PMID- 16418928
TI  - [Preparation and after-care in vitreoretinal interventions].

PMID- 16418929
TI  - [Some remarks on the precision of visual acuity measurements].
AB  - BACKGROUND: Visual acuity measurements are used to determine the course of
      diseases, treatment outcomes, consequences of accidents, and the occupational
      ability of a patient. The fact, that visual acuity depends both on visual
      function as well as on the circumstances of examination, is often understood more
      intuitively than explicitly. Precision and accuracy of visual acuity measurements
      must be kept in mind, and occasionally need to be quantified and statistically
      evaluated, to avoid clinical errors. METHODS: Factors influencing acuity
      measurements are analyzed. Using appropriate examples the precision of acuity
      measurements is evaluated and quantified with standard vision test charts and
      threshold or staircase procedures. Limits of confidence and limits of tolerance
      are described for the statistical evaluation of consecutive visual acuity
      measurements. RESULTS AND CONCLUSIONS: The statistical evaluation of standard
      procedures is relatively time consuming, as 3 to 4 standardized measurements are
      needed on first examination and on follow-up. Threshold and staircase methods,
      however provide more feasible data, due to the examination technique. All
      evaluation procedures described here, can only be applied with logMAR acuity
      readings.

PMID- 16418930
TI  - [Landolt C and snellen e acuity: differences in strabismus amblyopia?].
AB  - BACKGROUND: Assessment of visual acuity depends on the optotypes used for
      measurement. The ability to recognize different optotypes differs even if their
      critical details appear under the same visual angle. Since optotypes are
      evaluated on individuals with good visual acuity and without eye disorders,
      differences in the lower visual acuity range cannot be excluded. In this study,
      visual acuity measured with the Snellen E was compared to the Landolt C acuity.
      PATIENTS AND METHODS: 100 patients (age 8 - 90 years, median 60.5 years) with
      various eye disorders, among them 39 with amblyopia due to strabismus, and 13
      healthy volunteers were tested. Charts with the Snellen E and the Landolt C
      (Precision Vision) which mimic the ETDRS charts were used to assess visual
      acuity. Three out of 5 optotypes per line had to be correctly identified, while
      wrong answers were monitored. In the group of patients, the eyes with the lower
      visual acuity, and the right eyes of the healthy subjects, were evaluated.
      RESULTS: Differences between Landolt C acuity (LR) and Snellen E acuity (SE) were
      small. The mean decimal values for LR and SE were 0.25 and 0.29 in the entire
      group and 0.14 and 0.16 for the eyes with strabismus amblyopia. The mean
      difference between LR and SE was 0.55 lines in the entire group and 0.55 lines
      for the eyes with strabismus amblyopia, with higher values of SE in both groups.
      The results of the other groups were similar with only small differences between
      LR and SE. CONCLUSION: Using the charts described, there was only a slight
      overestimation of visual acuity by the Snellen E compared to the Landolt C, even
      in strabismus amblyopia. Small differences in the lower visual acuity range have
      to be considered.

PMID- 16418931
TI  - [Feasibility of prismatic correction of microesotropia using the measuring and
      correcting methodology by H.-J. Haase].
AB  - BACKGROUND: The "Measuring and Correcting Methodology after H.-J. Haase" is based
      on the assumption that a minute deviation from the orthovergence position
      (fixation disparity) indicates a difficulty to overcome a larger "vergence angle
      of rest". Objective recordings have, however, revealed that the subjective tests
      applied in the "Measuring and Correcting Methodology after H.-J. Haase" can
      mislead to the assumption of a fixation disparity, although both eyes are aligned
      exactly to the fixation point. QUESTION: How do patients with an inconspicuously
      small, yet objectively verified strabismus react to the "Measuring and Correcting
      Methodology by H.-J. Haase"? METHODS: Eight patients with a microesotropia
      between 0.5 and 3 degrees were subjected to the "Measuring and Correcting
      Methodology after H.-J. Haase. RESULTS: In all 8 patients, the prisms determined
      with the Cross-, Pointer- and Rectangle Tests increased the angle of squint,
      without reaching a full correction: the original angle prevailed. In the
      Stereobalance Test, prisms did not reduce the 100 % preponderance of the non
      squinting eye. The stereoscopic threshold was between 36 and 1170 arcsec in 7 out
      of the 8 subjects, and above 4000 arcsec in 1 subject. CONCLUSIONS: (1) In all 8
      patients, prisms determined with the "Measuring and Correcting Methodology by H.
      J. Haase" increased the angle of strabismus, without reaching bifoveal vision.
      This uniform result suggests that primary microesotropia cannot be corrected with
      the "Measuring and Correcting Methodology after H.-J. Haase" (2) A lacking
      contribution of the strabismic eye to the recognition of a lateral offset between
      stereo objects, as determined with the Stereobalance Test, does not imply a lack
      of binocular stereopsis.

PMID- 16418932
TI  - [Management of consecutive exotropia -- operative therapy and diplopia testing].
AB  - PURPOSE: The aim of this study was to investigate the diagnostic value of
      preoperative sensory testing on postoperative diplopia and to evaluate the dose
      effect relations of medial rectus muscle or unilateral recess/resect advancement
      procedures and their constancy. METHODS: A retrospective evaluation of 62
      operative cases of consecutive exotropia performed from 2001 to 2003 was carried
      out. Diplopia after prismatic correction and after converging by minus glasses
      was tested. In 47 cases a unilateral recess/resect procedure and in 15 cases an
      advancement of the medial rectus muscle were performed. The postoperative results
      were controlled one week and three months after operation by measuring the angle
      of squint by a prism cover test looking in five metres and in 33 cm. RESULTS: 22
      patients (36 %) had neither diplopia after prismatic correction of angle of
      squint nor after operation. The other 40 patients (64 %) experienced diplopia,
      but were not troubled by it. In all patients the whole amount of angle of squint
      was operated. Immediately after operation, 14 patients (23 %) experienced
      diplopia temporarily, which remained after 3 months in 9 patients, but all of
      them were not disturbed by it. In all patients the mean preoperative angle of -
      19 degrees was corrected by a mean operative amount of 11 mm, the mean
      postoperative angles were + 1.5 degrees after one week and - 2.6 degrees after
      three months with considerable variations of the results (standard deviations
      were about 5 degrees ). In 15 cases with advancement of the medial rectus muscle
      the dose-effect relation was 2 degrees per mm operative amount. After three
      months these patients become more divergent, the mean value was - 6 degrees , the
      dose-effect relation was reduced to 1.4 degrees /mm. The unilateral recess/resect
      operations were more constant: these became more divergent of 2.5 degrees only
      and their dose-effect relation remained more constant (after one week: 1.9
      degrees /mm, after 3 months: 1.7 degrees /mm). CONCLUSIONS: The diagnostic value
      of preoperative prismatic correction of the deviation is very limited. Even if
      diplopia can be provoked, the chance of disturbing diplopia is very low.
      Nevertheless, some guidelines for pre- and postoperative care are necessary to
      prevent double vision. The postoperative outcome is favourable for the patient
      after one operation. In cases of relapsing divergence a second operation is
      easily possible.

PMID- 16418933
TI  - [Surgical options in retraction syndrome].
AB  - BACKGROUND: A causative therapy for Duane's retraction syndrome, which is the
      most prominent example of connatal ocular misinnervation, does not exist. Eye
      muscle surgery is indicated in cases with manifest strabismus in primary position
      and an annoying compensatory head posture to maintain binocular single vision.
      Different surgical approaches to the different types of Duane's retraction
      syndrome, mostly on the affected eye but also on the fellow eye, are described in
      the literature. METHOD: We retrospectively analyzed the pre- and postoperative
      findings of 55 patients in whom we performed surgery because of Duane's
      retraction syndrome during the years 1999 to 2004. The type of retraction
      syndrome, the angle reduction in primary position and the reduction of head
      posture were evaluated in regard to the surgical procedure chosen. RESULTS: In 37
      cases surgery was primary. In 25 cases a single recession of the medial rectus
      (16 cases) or the lateral rectus (9 cases) muscle of the affected eye was
      performed. For a dose-response relationship of the one-muscle recessions, the
      mean angle reduction in the primary position was 2 pdpt (cm/m) per mm recession.
      The mean reduction of head posture was 1.5 degrees per mm recession. In 10 cases
      combined surgery on the affected eye was performed. The correlation between the
      mean angle reduction and the recession was 3 pdpt (cm/m) per 1 mm. CONCLUSION:
      Depending on the type of retraction syndrome, the angle in primary position, the
      head posture and the globe retraction, different surgical options exist which aim
      at rehabilitation of the patient suffering from Duane's retraction syndrome.

PMID- 16418934
TI  - [Influence of body position on ocular cycloposition in patients without binocular
      vision].
AB  - PURPOSE: Positionally induced cyclotorsion could be an important factor
      concerning correction of astigmatism in refractive surgery. Previous studies have
      shown no influence of body position on cycloposition in healthy subjects with
      normal binocular vision. METHODS: 10 subjects (median value of age 44.2 years)
      without binocular vision due to an organic eye disease or to strabismus were
      examined using three-dimensional video-oculography (3D-VOG). This non-invasive
      method can record changes in the position of both eyes simultaneously in the x-,
      y- and z-axes. The cycloposition of the eyes was recorded first in a seated
      position with both eyes open (test 1), then in a supine position with the right
      eye closed (test 2), then in a supine position with occlusion of both eyes (test
      3), and then in a supine position with both eyes open (test 4). In each of these
      4 situations, the eyes were recorded for 1 minute. Cyclovergence was calculated
      as the difference between the right and the left eye positions. RESULTS: The
      range of cycloposition of the right and left eye in all 4 tests was very small.
      95 % confidence intervals for cycloposition of the right and left eyes and for
      cyclovergence: cycloposition right eye/cycloposition left eye/cyclovergence:
      0.72;0.76/- 0.07;0.01/0.71;0.79 (test 1), 0.23;0.29/0.19;0.33/- 0.81;- 0.63 (test
      2), - 0.92;0.7/- 0.51;- 0.37/- 0.79;- 0.45 (test 3), 0.14;0.52/-
      0.07;0.31/0.59;0.21 (test 4). There was no statistically significant difference
      of the cycloposition between the 4 test situations. CONCLUSIONS: The
      cycloposition of the eyes does not significantly change between seated and supine
      positions of the body, either in subjects with, or without binocular vision. This
      means for refractive surgery that a correction of astigmatism, to be performed in
      the supine position of the patient, can be based on a measurement of the axis of
      astigmatism obtained in the seated position.

PMID- 16418935
TI  - [Adaptation of visual distortions in children with strabismic amblyopia following
      strabismus surgery and occlusion therapy].
AB  - BACKGROUND: Reduced visual acuity and deficient binocularity are well-known
      symptoms of amblyopia. Distortions of visual space perception were reported more
      recently in strabismic amblyopia. This study investigated whether strabismus
      surgery and occlusion therapy have an influence on these deficits in amblyopic
      children. MATERIALS AND METHODS: Two aspects of vertical alignment of amblyopic
      eyes, namely spatial distortion and spatial uncertainty, were investigated
      prospectively in 13 children (mean age 6 years 9 months) before and after
      strabismus surgery and in 12 children (mean age 6 years 11 months) during 6
      months of occlusion therapy. RESULTS: A different impact of the two types of
      therapeutic intervention was observed: a slight (statistically not significant)
      increase of uncertainty was the only change noticed postoperatively after 1 week,
      spatial distortions were not affected. During occlusion treatment, both clear
      shifts of alignment and a decrease of uncertainty occurred. CONCLUSIONS: The
      geometry of visual space of amblyopic children showed modifications due to
      altered visual experience during treatment, most obviously during occlusion
      therapy. These changes are evidence for unknown features of plasticity of the
      amblyopic visual system initiated by treatment.

PMID- 16418936
TI  - [Orbital diseases in childhood].
AB  - BACKGROUND: Orbital diseases in childhood are rare and differ from orbital
      lesions occurring in adults. Most paediatric orbital tumours are benign, but
      rapid tumour growth can nevertheless threaten vision or lives. PATIENTS:
      Retrospectively, we analyzed data of 41 consecutive patients with orbital
      disease, treated in our hospital between 2000 and 2004. The data was evaluated
      using descriptive statistics and case reports. RESULTS: All children (from
      neonatals up to 16 years of age) with orbital disease were included in the study.
      The most common benign disease of the entire collective was an epidermal cyst (n
      = 18), followed by orbital capillary haemangioma (n = 4) in children under 3
      years, and preseptal cellulitis in children older than 3 years. 5 patients were
      treated for malignant tumours, of which one patient under 3 years had an orbital
      metastasis of an abdominal neuroblastoma. CONCLUSION: Awareness of orbital
      diseases in childhood, as a rare entity, is crucial for timely diagnosis and
      appropriate treatment, to save the vision and lives of affected children.

PMID- 16418937
TI  - [Combination of epilenticular IOL-implantation and pars plana lentectomy in
      traumatic cataract patients].

PMID- 16418938
TI  - [Long-term results after epilenticular intraocular lens implantation following
      traumatic cataract].
AB  - BACKGROUND: The purpose of this study was to analyze the late postoperative
      outcome and complication rate after lensectomy with primary epilenticular
      intraocular lens (IOL) implantation for traumatic cataract. MATERIAL AND METHODS:
      We retrospectively reviewed the data of 11 patients who were operated on for
      traumatic cataract after penetrating or blunt ocular trauma between 1997 and
      2002. One patient developed cataract due to a large rupture of the posterior
      capsule after blunt trauma. Ten patients sustained a penetrating ocular injury
      with (7 eyes) or without (3 eyes) intraocular foreign body (IOFB). In all
      patients the IOL was implanted at the beginning of the operation into the ciliary
      sulcus in front of the opaque lens followed by pars-plana lensectomy and
      vitrectomy. RESULTS: The mean follow-up was 27.4 months. Eight eyes (72.7 %)
      achieved a final visual acuity of 0.5 or better. Major causes of limited visual
      acuity were central corneal scars causing irregular astigmatism. In all patients
      the IOL was safely and easily implanted into the ciliary sulcus. During the
      subsequent pars-plana lensectomy and vitrectomy as well as during the follow-up
      period all IOLs remained anatomically stable and well centered. In one patient
      PVR retinal detachment had to be treated by pars-plana vitrectomy with silicone
      oil tamponade. CONCLUSIONS: Epilenticular IOL implantation followed by pars-plana
      lensectomy is an easy and safe method to treat traumatic cataract in the setting
      of penetrating ocular trauma repair. It is associated with a favorable visual
      outcome and a low rate of postoperative complications.

PMID- 16418939
TI  - [Tumor regression and visual outcome after transpupillary thermotherapy (TTT) for
      malignant choroidal melanoma].
AB  - BACKGROUND: The aim of this study was to evaluate the course of tumor regression
      and visual impairment in choroidal melanomas treated by transpupillary
      thermotherapy (TTT) alone. PATIENTS AND METHODS: In a prospective, non-randomized
      analysis 26 patients suffering from primary choroidal melanoma (posterior to the
      equator with base < or = 12 and thickness < or = 4.5 mm) were treated with the
      TTT standard protocol and followed for 33 - 45 months. Fluorescein and ICG
      angiographies were performed initially and after tumor regression clinically.
      RESULTS: 22 tumors were significantly flattened after 1 - 3 TTT sessions. 4
      tumors required additional therapy with ruthenium plaque. Visual acuity remained
      unchanged or improved in 11 eyes. In all eyes fluorescein and indocyanine green
      angiography revealed a sharp demarcation of the heat-treated area. Except for
      macular edema and gliosis in 6 eyes no vascular or retinal tissue damage was
      noticed outside the treatment zone. In the periphery of the treatment zone all
      eyes showed residual choriocapillaries remaining perfused. During follow-up 2
      eyes revealed tumor regrowth at the posterior margin of the scar, which was
      successfully managed by TTT or a ruthenium plaque. 2 eyes developed late
      choroidal neovascularizations (CNV) in the heat-treated area. One patient died of
      liver metastases. CONCLUSIONS: Fluorescein and indocyanine green angiographic
      findings after TTT for small choroidal melanomas suggest that the tissue damage
      in the choroidal layer is less effective, which perhaps can lead to a higher rate
      of tumor regrowth. Development of choroidal neovascularization may be a sign of
      late heat-induced side effects of TTT.

PMID- 16418940
TI  - [Ocular involvement in MuSK antibody-positive myasthenia gravis].
AB  - BACKGROUND: Antibodies (Ab) against the acetylcholine receptor (AChR) are found
      in 80 - 90 % of generalized myasthenia gravis (MG), but only in 50 % of pure
      ocular MG. Furthermore, Ab against the muscle-specific receptor tyrosine kinase
      (MuSK) were detected in 38 - 54 % of patients with AChR-Ab-negative
      ("seronegative") MG, but not in pure ocular MG. METHODS: 2 case reports have been
      analysed: two patients (42 years old and 61 years old) with primary ocular MG
      were studied. Both patients complained of fluctuating bilateral ptosis and double
      vision lasting for 2 to 3 months. RESULTS: AChR-Ab were negative but MuSK-Ab were
      clearly positive. In spite of treatment with pyridostigmine and prednisolone, the
      symptoms in patient 1 generalized within 4 weeks causing dysphagia, limb muscle
      weakness and respiratory crisis. Symptoms immediately responded to
      plasmapheresis. Patient 2 clearly improved under treatment with pyridostigmine,
      methylprednisone, and azathioprine. There was no generalization within a course
      of 12 months. CONCLUSIONS: Both cases clearly indicate that MuSK-Ab can be found
      in primary isolated ocular MG lasting for 2 to 3 months. In a primary ocular
      manifestation of MG the detection of MuSK might indicate the risk for subsequent
      generalization and might have implications for immunosuppressive therapy.
      Therefore, seronegative MG requires testing for MuSK-Ab.

PMID- 16418941
TI  - [The influence of geometric visual illusions on saccadic eye movements].
AB  - BACKGROUND: The aim of this study was to investigate whether visually perceived
      length differences of Mueller-Lyer figures result in amplitude differences of
      saccadic eye movements along the figures. METHODS: Video recordings of eye
      movements were obtained from 35 healthy volunteers (aged 18 - 30 years) when
      scanning the endpoints of Mueller-Lyer targets. RESULTS: Saccades between the
      ends of lines with inward-pointing arrowheads had significantly greater
      amplitudes than saccades between the ends of lines with outward-pointing
      arrowheads. This bias was observed for both horizontal and vertical target
      orientations, and was maintained with a smaller amplitude, after fixation periods
      were extended from 1 s to 4 s. CONCLUSIONS: Changes in length perception by
      visual illusions correspond with changes in the amplitude of saccadic eye
      movements. Therefore, recordings of saccadic eye movements offer the opportunity
      to assess changes in visual object perception based on changes of central image
      processing at the cortical level.

PMID- 16418942
TI  - [Simulating the outcome of ptosis and squint surgery with digital photomontage].
AB  - BACKGROUND: When being informed preoperatively about the risks and prospects of
      ptosis and squint surgery patients may wish to see pictures of the possible
      outcome. In most cases pre- and postoperative prints of patients with similar
      problems will be sufficient. But, to come to a decision, some patients need
      portrait prints of their own face modified to show the changes that could be
      produced by the surgery proposed. Such photo prints can be rather easily produced
      with modern computer and software equipment. MATERIALS AND METHODS: Portrait
      photos have been shot with a digital camera and have been modified in a personal
      computer with image processing software. RESULTS: Technique and outcome are shown
      with two case studies. One patient had a slight asymmetry of the upper lids after
      a bilateral anterior fat resection for dysthyroid exophthalmus. The second
      patient suffered from a considerable pseudoexotropia caused by retinopathy of
      prematurity. In both cases the probable result could be simulated
      photographically to an extent that decision making became rather easy.
      CONCLUSIONS: Phototechnical simulation of surgical outcome may be useful to
      produce better information for some patients.

PMID- 16418944
TI  - [Quality of care and extent of complications in a population-based sample of
      patients with type 2 diabetes mellitus. The KORA Survey 2000].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to analyse health care
      processes and outcomes in type 2 diabetes in a representative population sample
      of persons, aged 25-74 years, in the region of Augsburg, Germany. PATIENTS AND
      METHODS: Based on the KORA Survey 2000, indicators of health care services and
      outcomes were analysed for all study subjects with known type 2 diabetes (n=149;
      80 males (54%)) , mean age 62 +/- 9 years; total random population sample: 4,261
      persons). Means and prevalences were calculated, including 95% confidence
      intervals (CI). Associated factors were analysed using multivariate regression
      models. RESULTS: 57% of the patients had not received adequate drug treatment
      concerning hypertension and 43% concerning hypercholesterolemia. 63% (CI: 54-70
      %) and 38% (CI: 30-47%), respectively, reported that their eyes or feet had been
      examined during the past 12 months. 47% (CI: 39-56%) had been instructed about
      their diabetes. 69% (CI: 61-76%) of the subjects did not know the term "HbA(1c)",
      the proportion being higher among subjects without diabetes education or those of
      a low social status. 13% (CI: 8-20%) of the subjects had been told by their
      medical practitioner that they had a retinopathy, 5% (CI: 2- 10%) a foot ulcer,
      19% (CI: 12-28%) proteinuria. Two persons were blind, one had been on renal
      dialysis, and 5% (CI: 2-10%) had undergone amputation of a limb. 6% (3-12%) had
      at least one of the end-stage diabetic complications. The mean HbA(1c) was 7.2 +/
      1.6%, significantly higher in those with a diabetes for >10 years. CONCLUSIONS:
      The population-based data regarding indicators of type 2 diabetes care processes
      and outcome in a defined region in Germany show that the treatment of
      hypertension and hypercholesterolemia was highly inappropriate, as was the
      frequency of medical control investigations. The high proportion of subjects who
      did not know the term "HbA(1c)" was striking, particularly among those of a low
      social status. A significant proportion had severe late complications. The mean
      HbA(1c), however, was better than had been reported in some previous German
      practice-based studies.

PMID- 16418945
TI  - [Intra-arterial and intramuscular transplantation of adult, autologous bone
      marrow stem cells. Novel treatment for therapy-refractory peripheral arterial
      occlusive disease].
AB  - HISTORY AND CLINICAL FINDINGS: A 62-year-old man had limb ischemia in stage IIb
      (Fontaine's classification). After surgical and interventional measures the right
      superficial femoral artery had remained occluded for more than one year. The
      patient's walking distance was only 100 meters. It was therefore decided to do a
      combined intraarterial and intramuscular transplantation of stem cells into the
      right limb. INVESTIGATIONS: Before and 10 weeks after the transplantation
      noninvasive tests, namely walking distance, ankle-brachial index at rest and
      during exercise, occlusion plethysmography and capillary venous oxygen saturation
      were measured. The patient was also asked to fill in a questionnaire of his
      symptoms. THERAPY AND RESULTS: After harvesting the patient's bone marrow the
      mononuclear cell fraction was separated (109.8 x 10(6)). Afterwards 10 ml of the
      cell suspension were injected into the right superficial femoral artery and 5 ml
      each of the suspension was injected into 5 different locations of the quadriceps
      femoris and the gastrocnemius muscles. After 10 weeks" follow-up a seven-fold
      improvement of walking distance and an increase of tissue oxygen saturation of
      more then 50% were recorded. The ankle-brachial index at rest remained unchanged,
      but on exercise it increased by 24%. CONCLUSION: The combined intraarterial and
      intramuscular transplantation of human autologous bone marrow stem cells may be a
      novel and clinically feasible treatment for patients with severe chronic limb
      ischemia. The success of this approach may be the result of increased neo
      angiogenesis, especially of the small muscle-supplying vessels.

PMID- 16418946
TI  - [Fibrinogen-guided thrombolysis with urokinase of a portal and mesenterial venous
      thrombosis during an acute episode of ulcerative colitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 23-year-old woman with a 5-year history of
      ulcerative colitis was admitted to our hospital because of bloody diarrhea. Two
      years previously she had undergone a hemicolectomy for a right colonic stricture.
      A recurrence of inflammatory bowel disease was suspected and treatment with
      prednisolone begun. The symptoms improved gradually, but 7 days later she
      complained of lower abdominal pain. Physical examination revealed a soft abdomen,
      but bowel sounds were reduced. INVESTIGATIONS: The abdominal X-ray was
      unremarkable, but ultrasonography revealed moderate ascites and no blood flow in
      the portal vein on Doppler examination. The spleen was slightly enlarged.
      Contrast-enhanced abdominal magnetic resonance imaging (MRI) was performed
      immediately, revealing thrombosis of the portal and mesenteric veins. TREATMENT
      AND COURSE: As there was no suggestion of intestinal necrosis, laparatomy was not
      considered necessary. Intravenous thrombolytic treatment with urokinase was given
      continuously (bolus of 250,000 units, followed by 200,000 units per hour), in
      order to lower the fibrinogen level to 100 - 150 mg/dl, together with
      unfractionated heparin, maintaining the activated partial thromboplastin time
      between 60 and 85 seconds. The thrombolytic treatment had to be stopped several
      times because of bloody diarrhea, but no transfusion was necessary. Two days
      after the start of thrombolytic treatment the abdominal pain and ascites ceased.
      Doppler sonography now demonstrated hepatopetal flow in the previously occluded
      portal vein. 4 days later, MRI revealed that the thrombus in the portal vein had
      dissolved and the portal vein was fully patent. The mesenteric vein was partially
      perfused, a residual thrombus extending into the portal vein. Tests for
      thrombophilia were negative. The thrombolytic therapy was stopped after 112 hours
      and the patient was treated with oral anticoagulation for 6 months. The patient
      recovered completely, with no evidence of portal hypertension during the
      following 6 months. CONCLUSIONS: Thrombolysis with urokinase, guided by the level
      of fibrinogen, may be an alternative, semi-invasive treatment option in acute
      thrombosis of the portal and mesenteric veins.

PMID- 16418948
TI  - [Glomerulonephritis].

PMID- 16418951
TI  - [Traditional contraindications to the use of metformin -- more harmful than
      beneficial?].
AB  - For fear of lactic acidosis the currently listed contraindications to the use of
      metformin exclude a large number of people with type 2 diabetes from efficacious
      anti-hyperglycemic and cardioprotective treatment. Yet recent data call the
      traditional contraindications to metformin into question. As the incidence of
      lactic acidosis in patients with type 2 diabetes is the same with or without
      metformin therapy (about 9 per 100,000 patient years) there is no evidence that
      metformin therapy is associated with an increased risk of lactic acidosis.
      Similarly, despite disregard internationally of major metformin
      contraindications, there has been no corresponding increase in the incidence of
      lactic acidosis. Metformin treatment of elderly diabetics with multiple
      comorbidities and explicit contraindications has led to significantly better
      clinical parameters in them than in the control group without metformin; and
      there were no cases of lactic acidosis. The two groups did not differ with regard
      to progression of renal failure, patient-oriented endpoints or overall mortality.
      Compared with its predecessors phenformin and buformin, metformin is considerably
      less lipophilic and has a shorter plasma half-life; it is eliminated renally in
      unchanged form. In type 2 diabetics treated with metformin -- even those over 70
      years of age and those in mild renal failure -- no relevant increases in lactate
      levels were found. In patients with lactic acidosis there was no correlation
      between the levels of metformin and lactate. The prognosis of lactic acidosis is
      determined less by the serum concentrations of metformin and lactate than by the
      hypoxia caused by the underlying disease and comorbidities. These findings raise
      doubts about the significance of metformin in the pathogenesis of lactic
      acidosis. On the basis of the current data, advanced age per se, mild renal
      impairment and stable heart failure can no longer be upheld as contraindications
      to the use of metformin. It should be safe to withdraw metformin the evening
      before radiological examinations with intravenous contrast media or surgical
      procedures under general anaesthesia in diabetics with normal renal function.

PMID- 16418953
TI  - Local bleomycin injection in the treatment of lymphangioma.
AB  - AIM: We report here our experience with local bleomycin injection in
      lymphangioma. PATIENTS AND METHODS: Nine patients with lymphangioma were treated
      with locally injected bleomycin and followed prospectively. We performed an
      ultrasound study in all cases to delineate the size, location, nature, and number
      of compartments of the cyst prior to the injection. Under ultrasound guidance,
      the content of the cystic cavity was aspirated and 1 - 3 mg/kg bleomycin were
      injected. The patients were revisited monthly. No attempt at re-injection was
      made as long as the mass continued to decrease in size. RESULTS: Patients
      consisted of 4 boys and 5 girls aged between 14 days and 6 years. The
      localisation of the mass was cervical in 6, cervical, sublingual, and lingual in
      1, axillary in 1 and axillary and thoracic in 1. In six children, the mass
      disappeared totally after a single injection. In one patient a second injection
      was needed, and surgical excision was performed in two patients with residual
      solid component. No complication related to bleomycin was seen. CONCLUSION: Local
      application of bleomycin in children with lymphangioma is a simple, safe, and
      effective method. In the majority of cases, total healing may be achieved with a
      single injection.

PMID- 16418954
TI  - Electrocardiographic and biochemical evidence for the cardioprotective effect of
      vitamin E in doxorubicin-induced acute cardiotoxicity in rats.
AB  - BACKGROUND/AIMS: Cardiotoxicity is a major side effect limiting the use of
      doxorubicin, a potent chemotherapeutic agent, in the treatment of pediatric
      neoplastic diseases. The effect of vitamin E in doxorubicin-induced
      cardiotoxicity in rats has been studied. METHODS: Eighteen Wistar male rats (age
      60 - 100 days, weighing 175 - 260 g) were divided into three groups of six: group
      A (controls); group B (doxorubicin-treated rats); and group C (pretreatment with
      a high dose of vitamin E followed by doxorubicin treatment). The weights of the
      rats were measured daily. The rats were sacrificed seven days after the last dose
      of doxorubicin injection by an overdose of ether. Electrocardiogram (ECG)
      tracings were recorded before sacrificing the rats. The ECG tracings were then
      evaluated for rate and rhythm disorders by assessing the PR, ST, and QT
      intervals. In group B rats ECG tracings were taken three days after the
      completion of doxorubicin treatment, while in group C rats they were taken at the
      end of 2 weeks of vitamin E pretreatment and again 3 days after the completion of
      doxorubicin treatment. Serum levels of creatine phosphokinase (CPK-MB), lactic
      dehydrogenase (LDH), and serum glutamic oxaloacetic transaminase (SGOT) were
      assessed from an intracardiac blood sample taken at the time of sacrificing the
      rat. RESULTS: Mean weight ranged from 205 - 226 g. Mean total dose of doxorubicin
      in groups B and C ranged from 36 - 38 mg. The PR intervals in the three groups
      were recorded as 0.006, 0.070, 0.057 s for groups A, B, and C, respectively (p =
      0.0024) and the QT interval as 0.023, 0.120, 0.088 s in groups A, B, and C,
      respectively (p = 0.00089). The ST elevation due to doxorubicin toxicity was
      significantly reversed by vitamin E treatment. The difference in the levels of
      CPK-MB and LDH between the three groups was found to be statistically
      significant. Serum SGOT levels also varied between the three groups but were not
      statistically significant. CONCLUSION: Vitamin E pretreatment prevented the PR,
      QT, and ST segment changes caused by doxorubicin. Vitamin E treatment helped to
      decrease the levels of CPK-MB and LDH that were increased due to myocardial
      damage caused by the doxorubicin. There is sufficient evidence to believe that
      vitamin E protects the rat myocardium from doxorubicin-induced damage.

PMID- 16418955
TI  - Use of synaptophysin immunohistochemistry in intestinal motility disorders.
AB  - The purpose of this study was to describe synaptophysin (SY) immunoreactivity in
      colonic specimens from patients with Hirschsprung's disease (HD), chronic
      constipation (CC), or anal atresia (AA). This membrane protein is specific for
      the synaptic vesicles in the central and peripheral nervous system and
      responsible for neurotransmission. Biopsy specimens of the intestinal wall were
      obtained from 18 patients (age range, 2 days to 7 years). Immunohistochemistry
      was performed using rabbit anti-human antibodies specific for synaptophysin
      (DAKO). In the ganglionic colon of HD patients and others the immunoreactivity of
      SY-positive synapses was abundantly present in the smooth muscle layers. Distinct
      immunoreactivity showed ganglion cells and nerve fibers inside circular and
      longitudinal muscle layers. In some non-HD patients' colonic specimens SY
      positive synapses were present in the muscularis mucosae. In the aganglionic
      colonic segment of HD-patients no immunoreactivity of synapses and ganglions was
      seen. In the transition zone, where ganglion cells appeared sporadically,
      synapses were very rarely present. In two patients from the CC group the amount
      of visualized synapses was clearly smaller and the concentration of ganglion
      cells within ganglions in these cases was much lower than usual (but still within
      normal ranges). In the AA group in the distal part of the atretic rectum (at the
      place where the fistula was cut) SY-positive synapses were present in smooth
      muscle layers and small dysplastic ganglions were seen in the submucosal and
      muscular region, but not in large numbers. These patients had a normal
      distribution of ganglion cells and synapses at the place of colostomy.
      Synaptophysin immunohistochemistry is an indirect labeling method with a high
      detection rate for intestinal ganglion cells by demonstrating their synapses.
      Changed intestinal distributions of SY-positive synaptic vesicles usually
      accompany colonic ganglion cell disorders. The pattern of SY-positive synapses
      distribution in circular and longitudinal colonic muscles and intermuscular
      ganglions can reflect functional disturbances of large bowel motility and could
      be helpful in the description of the innervation status of colonic specimens in
      HD patients.

PMID- 16418956
TI  - A clinical analysis of prognostic parameters of survival in children with
      congenital diaphragmatic hernia.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) still has a high mortality
      because of accompanying lung hypoplasia and persistent pulmonary hypertension.
      Although prognostic parameters based on perinatal measurements have been
      proposed, our ability to accurately predict the surgical results remains
      insufficient. METHODS: We treated 55 infants with CDH from 1981 to 2004. Among
      them, 46 patients presented respiratory distress within the first 24 hours of
      life. Results of surgical treatment in the 46 infants were retrospectively
      correlated with gender, birth weight, gestational age at diagnosis, laterality,
      cardiac anomalies, diaphragmatic defect area, contents of herniated viscera, and
      the great vessel diameters measured by echocardiography. RESULTS: Out of 46 CDH
      neonates, 27 (58.7 %) survived and 19 (41.3 %) died aged 3 to 17 days. Non
      survivors had a significantly larger diaphragmatic defect and more frequent liver
      herniation. Out of possible predictive parameters studied, an index of the main
      pulmonary artery (cross-sectional area/diaphragmatic defect area ratio) most
      closely correlated with the surgical outcomes. CONCLUSIONS: The postoperative
      prognosis of CDH infants does not depend only on pulmonary hypoplasia, but also
      on other factors including the magnitude of abdominal visceral herniation. In
      this series of patients, the most reliable prognostic predictor was a clinical
      index reflecting the degree of both pulmonary hypoplasia and diaphragmatic
      maldevelopment.

PMID- 16418957
TI  - Fundoplication in paediatric surgery: a survey in 40 German institutions.
AB  - BACKGROUND: There is no generally accepted standard surgical approach to
      gastrooesophageal reflux disease (GERD) at present. However, laparoscopic
      fundoplication has been advocated to be the procedure of choice for
      gastrooesophageal reflux disease in children. We aimed to assess the standards of
      the diagnostic workup and operative techniques in paediatric surgical
      institutions in Germany. MATERIAL AND METHODS: A questionnaire including 14 items
      was sent to all 71 departments of paediatric surgery in Germany. Forty (56 %)
      took part in the survey. Concepts of routine diagnostic workup, operative
      techniques, number of procedures, and conversions were assessed. RESULTS: The
      average annual frequency of fundoplications was less than 20 in 36 units (90 %).
      Experience with laparoscopic fundoplication was present in 24 institutions (60
      %). In 19 out of these (79 %) fewer than 50 laparoscopic fundoplications had been
      performed altogether up to the time of the survey. Out of 584 fundoplications
      performed in the year 2002, 184 (32 %) had been done laparoscopically. The ratio
      of conventional versus laparoscopic fundoplication was 170/130 (57/43 %) in
      academic, and 226/54 (81/19 %) in non-academic departments. The preferred
      technique of fundoplication, irrespective of the approach, was the Nissen wrap in
      28 (70 %) of the departments. The number of paediatric surgeons performing
      laparoscopic fundoplication was 1 - 2 in 16 institutions (67 %), 3 or 4 in 6 (25
      %), and 5 in 2 (8 %) departments. The conversion rate was reported to be less
      than 5 % in 15 departments (63 %), and 5 - 10 % in 3 (13 %). CONCLUSION: The
      laparoscopic approach for surgical repair of GERD in children is not yet
      generally accepted in Germany. In most departments, training remains problematic
      due to low numbers of procedures. However, the feasibility of laparoscopic
      fundoplication in Germany is excellent, with a low rate of conversions.

PMID- 16418958
TI  - Clinical characteristics and the prognosis of rhabdomyosarcoma - a report from
      the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.
AB  - AIM: There have been no nationwide group studies for patients with
      rhabdomyosarcoma in Japan. This study aims to assess the actual state of
      treatments and their outcome. PATIENTS AND METHODS: From 1982 to 1996, 79
      rhabdomyosarcomas were registered by the Study Group for Pediatric Solid
      Malignant Tumors in the Kyushu Area. The prognostic factors and treatments were
      assessed based on the 5-year survival rate. The staging was done according to the
      Intergroup Rhabdomyosarcoma Study (IRS) Clinical Grouping Classification.
      RESULTS: The 5-year survival rate for all patients was 39.1 %. The survival rates
      for each factor were as follows, according to 1) group; 77.8 % for Group I, 51.9
      % for Group II, 33.7 % for Group III, and 20.2 % for Group IV; 2) primary site:
      56.3 % for the head and neck, 43.8 % for the parameningeal region, 12.5 % for the
      extremity, 58.3 % for the genitourinary region, and 30.5 % for the others; 3)
      histology: 35.8 % for the embryonal type, 36.8 % for the alveolar type.
      CONCLUSIONS: Altogether, the outcome of this study was poor. To improve outcomes,
      a new nationwide group study for rhabdomyosarcoma, which we belong to, has just
      started in Japan.

PMID- 16418959
TI  - Surgical complications in the treatment of Wilms' tumor.
AB  - We present our data on the treatment of Wilms' Tumor (WT) with an emphasis on
      both the positive effect and the adverse effect of preoperative chemotherapy with
      regard to surgical intervention. From 1980 to 2000 70 children were treated. 57 %
      received preoperative chemotherapy (ChTx) and 43 % were operated on primarily. 75
      % of the tumors responded to ChTx with significant shrinkage of the size. After
      preoperative ChTx 54 % of the cases were regrouped as stage I, whereas after
      primary operation 46 % of the patients were grouped as stage I, thus indicating a
      downstaging with preoperative ChTx. In 8 % of the patients with preoperative
      chemotherapy intraoperative complications occurred with a rupture of the tumor in
      1 case. In contrast, there were intraoperative complications in 25 % of the
      patients with a primary operation with rupture of the tumor in 3 cases. 1 child
      (1.5 %) was treated with chemotherapy who did not have a Wilms' tumor but a
      benign nephroma (CMN). 3 cases had a clear cell sarcoma (CCSK) and in one case
      histology revealed a rhabdoid tumor (MRTK). In one case of CCSK only histology of
      the metastases disclosed the correct diagnosis. The rate of postoperative
      complications such as ileus was the same for both groups. Irrespective of the
      known adverse effects such as changing tumor histology, which may affect the
      correct staging, and the remaining risk of an initial inadequate treatment, our
      data show that the regimen of preoperative chemotherapy as proposed by the SIOP
      study should not be abandoned. However, the relatively small number of our
      patients does not allow a significant statement to be made but confirms the
      results of past SIOP studies.

PMID- 16418960
TI  - Tubularized incised plate (TIP) urethroplasty (Snodgrass) in primary hypospadias
      repair.
AB  - In the past TIP urethroplasty became a preferred technique for distal hypospadias
      repair, and subsequently gained worldwide popularity and acceptance. The
      procedure gives good functional results and a cosmetic appearance that is
      superior to that obtained by flip-flap or onlay preputial flap repairs. In
      addition, this procedure is associated with a fairly low rate of complications.
      From 06/2000 to 04/2004 we performed 100 primary TIP urethroplasties in patients
      with distal hypospadias. The age of the patients at the time of surgical
      correction was 16 months to 10 years with a mean of 41.4 months. All patients
      underwent the procedure under general anesthesia supplemented by additional pain
      management with a penile block anesthesia or caudal anesthesia. The surgical
      technique is described. During follow-up (23.5 months) we observed 2 types of
      complications: formation of a urethrocutaneous fistula (5 pts., 5 %) and
      formation of meatal stenosis (17 pts., 17 %) with a steady decrease with no
      stenosis formation in the last 8 months of this series. A key point might be the
      length of the dorsal incision of the urethral plate which should not touch the
      dorsal lip of the anticipated neomeatus. There were no other complications, and
      the cosmetic results were good in all cases.

PMID- 16418961
TI  - The shoelace method in congenital aplasia of the scalp and skull.
AB  - Aplasia cutis congenita (ACC) is an uncommon skin disorder characterised by the
      absence of some or all layers of the skin. It may involve any part of the body,
      but is most common in the scalp. Some scalp lesions are associated with a defect
      of the underlying skull or even dura. Small superficial lesions heal
      spontaneously. Options available for larger defects and those involving the skull
      include conservative management, skin grafts, composite grafts, local scalp or
      pericranial flaps, and free microvascular transplants. This case report presents
      a delayed primary closure of a scalp and skull defect with the shoelace method
      and a temporary skin graft. The method is simple, gives an excellent cosmetic
      result, and can be used in moderately sized defects, where a direct suture is not
      possible.

PMID- 16418962
TI  - An intra-thyroid thyroglossal duct cyst.
AB  - Thyroglossal duct cysts can be found in several different locations, although
      intra-thyroid presentations are rare. We present the case of an 11-year-old
      patient with a visible neck mass on the right thyroid lobe. On sonogram, it was
      consistent with a unilocular cyst measuring 2 centimeters in diameter. The cyst
      did not take up the radioisotope during a gammagram. Fine needle aspiration
      cytology suggested a diagnosis of thyroglossal duct cyst. At surgery, we found
      that there were no lesion-dependent thyroglossal tracts; we therefore performed a
      simple enucleation of the cyst, sparing the rest of the gland. The pathologic
      examination confirmed that it was an intra-thyroid thyroglossal duct cyst. After
      8 months of follow-up, the patient has remained without complications of any kind
      or recurrence. Only four prior cases of intra-thyroid thyroglossal cysts have
      been described in the pediatric population. Half of them presented with a typical
      thyroglossal tract crossing the hyoid and the other half presented an isolated
      cyst. It is highly unlikely that a cold, cystic, thyroid mass in a child is a
      thyroglossal duct cyst. Diagnosis is made on the basis of fine needle aspiration
      cytology and the lesion is treated surgically. A thyroglossal tract must be
      methodically sought out during intervention, although they frequently do not
      exist.

PMID- 16418963
TI  - Delayed surgery in pericardial teratoma with neonatal hydrops.
AB  - Timing of neonatal surgery in cases of pericardial teratoma with hydrops is not
      standardised. We report two cases of hydropic premature newborns with pericardial
      teratoma in which surgery was delayed until respiratory and haemodynamic
      stabilisation. Mature teratoma was removed on day 3. The newborns were weaned
      from the ventilator on postoperative day 5 and 10, respectively. Both infants
      were doing well at 18 months, suggesting delayed surgery may be feasible and
      effective.

PMID- 16418964
TI  - Gastroschisis and biliary atresia in a neonate: uncommon presentation or common
      precipitant.
AB  - We report here on a newborn infant who initially presented with a history of
      gastroschisis, abdominal distension, and jaundice. Further studies revealed that
      the child had findings consistent with extrahepatic biliary atresia (EHBA). The
      child later developed hepatic failure and subsequently expired. The purpose of
      this case report is to discuss the pathogenesis of each disease process and to
      identify any commonality between the pathogenesis of gastroschisis and EHBA.

PMID- 16418965
TI  - Covered exstrophy with visceral sequestration: case report and review of
      literature.
AB  - We report a case of a male newborn with asymmetrical epispadic diphallia and
      congenital urethral fistula, and exomphalos minor. A segment of bowel was
      attached in the region of the pubis; with no communication to the underlying
      bowel. This was excised; histological examination revealed this to be a colonic
      remnant. The excision of the examphalos minor and approximation of the pubis and
      the rectus sheath over the bladder was also done; urethroplasty is planned at a
      later date. A comprehensive review of the available literature revealed only
      eight such cases before this; the possible embryology is discussed.

PMID- 16418966
TI  - Uterus didelphys with obstructed hemivagina and multicystic dysplastic kidney.
AB  - Mullerian malformations include a broad range of anomalies, resulting from the
      incomplete formation and/or differentiation of the Mullerian ducts. The uterus
      didelphys with obstructed hemivagina represents the result of a lateral nonfusion
      of the Mullerian ducts with asymmetric obstruction, and it is almost always
      associated with renal agenesis. We report a case of incidental discovery of this
      anomaly in a 12-year-old girl during a routine renal ultrasound. A right
      multicystic dysplastic kidney had been detected in the prenatal and neonatal
      period with no evidence of uterine anomaly. Postnatal ultrasound examinations
      performed regularly had never detected either right renal tissue or the uterine
      anomaly before menarche. Hematocolpos after menarche made uterine anomaly
      detection easier. Magnetic resonance imaging performed to evaluate the uterine
      malformation detected a dysplastic right kidney. We review the present knowledge
      and recommendations for the diagnosis and treatment of this anomaly, and we
      emphasize the use of magnetic resonance imaging not only for the evaluation and
      classification of Mullerian malformations, but also for the detection of the
      persistence of renal tissue missed with other studies.

PMID- 16418967
TI  - Unusual presentation of McKusick-Kaufman syndrome in a female Bedouin Arab baby.
AB  - McKusick-Kaufman syndrome is a rare, autosomal, recessive disorder characterized
      by hydrometrocolpos, post-axial polydactyly, and congenital heart disease. Less
      than one hundred cases have been reported in the English literature to date,
      mainly in the Amish population; sporadic cases have also been described. We
      present a case of an Arab Bedouin girl who presented with features resembling
      this syndrome.

PMID- 16418968
TI  - Double urethral obstruction in a neonate - a case report.
AB  - Posterior urethral valves are the most common cause of lower urinary tract
      obstruction in a male child, generally occurring as an isolated anomaly.
      Congenital anterior urethral diverticulum, although less common, can also cause
      urethral obstruction. We report a rare combination of the two anomalies in which
      the proximal, more severe anomaly prevented the initial expression of the other.

PMID- 16418970
TI  - [Epidemiology of uveitis in juvenile idiopathic arthritis from a national
      paediatric rheumatologic and ophthalmologic database].
AB  - BACKGROUND: Uveitis is a frequent and potentially vision-threatening
      manifestation of juvenile idiopathic arthritis (JIA). There are only a few
      population-based studies providing data on the frequency and severity of uveitis.
      METHODS: Documentation of patients with JIA was collected in a national database.
      An analysis of the paediatric rheumatologic and ophthalmologic data collected
      from all patients that were included in 2002 was performed. RESULTS: Uveitis was
      documented in 12 % of a total of 3271 JIA patients: extended oligoarthritis (25
      %), persistent oligoarthritis (16 %), seronegative polyarthritis (4 %),
      seropositive polyarthritis (2 %), psoriatic arthritis (10 %), enthesitis-related
      arthritis (ERA) (7 %), systemic arthritis (1 %), other arthritis forms (11 %).
      Ophthalmologic data were available from 115 uveitis patients (28 %). Mean age at
      onset of uveitis was 5.2 (SD 3.2) years. JIA patients with uveitis were
      significantly younger at onset of arthritis (3.8 vs. 7.0 years), and were more
      often girls (74 vs. 63 %) or ANA-positive (86 vs. 42 %) than the patients without
      uveitis. Uveitis complications were present in 45 % at initial presentation of
      uveitis. After a mean duration of 5.6 years, complications were noted in 56 %,
      and included band keratopathy (29 %), posterior synechiae (27 %), cataract (26
      %), glaucoma (8 %), and macula oedema (6 %). Final visual acuity was less than
      20/50 in 31 % and less than 20/200 in 12 % of eyes. In patients with uveitis,
      immunosuppressive or immunomodulatory drugs were used significantly more often
      than in patients without uveitis (75 % vs. 43 %). CONCLUSIONS: The nationwide
      data documents the spectrum of uveitis in patients with JIA, the complications
      and the therapy for uveitis. The high rate of uveitis complications at the time
      of diagnosis points out the need for early ophthalmologic screening and therapy,
      and for a close collaboration between ophthalmologist and paediatric
      rheumatologist.

PMID- 16418973
TI  - Research methodology and epidemiology of relevance in recurrent pregnancy loss.
AB  - With respect to recurrent pregnancy loss (RPL), unfortunately there is very
      little consensus about which investigations are useful for identifying causes and
      evaluating the prognosis, and also about which treatments are effective. In this
      review, arguments are given for the claim that this lack of consensus may mainly
      be because studies in the field of RPL have yielded very heterogeneous results.
      This heterogeneity, in the authors' belief, is caused by the scientists' lack of
      appreciation, when they do research, of important epidemiological knowledge about
      RPL (e.g., about the multifactorial background for most of the RPL cases and the
      importance of matching/adjusting for a series of prognostic variables when groups
      are mutually compared). Furthermore, many studies in RPL contain methodological
      flaws that are sometimes severe. A series of important epidemiological features
      of RPL is highlighted in the review and the most important methodological
      pitfalls, many of them specific for RPL research, are discussed. Advice is given
      about to how to avoid the pitfalls in order that the validity of the studies can
      improve for the benefit of the patients.

PMID- 16418974
TI  - Genetics of recurrent pregnancy loss.
AB  - Recurrent pregnancy loss (RPL) is a devastating reproductive problem affecting
      approximately 5% of couples trying to conceive. Genetic factors appear to be
      highly associated with reproductive loss. In this article, genetic factors are
      reviewed in terms of random numerical chromosome errors in miscarriage specimens
      and carriers of structural chromosome rearrangements that may result in
      unbalanced chromosome errors in pregnancies. Recently, research has generated
      interest in genetic markers for recurrent loss such as skewed X-chromosome
      inactivation and human leukocyte antigen-G polymorphisms. Assisted reproductive
      technologies (specifically, preimplantation genetic diagnosis) have been offered
      to couples with recurrent pregnancy loss; however, more data need to be evaluated
      before routine use can be advocated. Management of genetic factors in RPL should
      include therapy based on the highest level of evidence, genetic counseling, and
      close monitoring of subsequent pregnancies.

PMID- 16418975
TI  - Anatomic factors in recurrent pregnancy loss.
AB  - Anatomic uterine defects are present in 15% of women evaluated for three or more
      consecutive spontaneous abortions. These anatomic abnormalities can be classified
      as congenital or acquired. In addition to pregnancy loss, uterine malformations
      appear to predispose women to other reproductive difficulties including
      infertility, preterm labor, and abnormal presentation. These poor reproductive
      outcomes resulting from uterine septum, intrauterine adhesions, polyps, and
      fibroids are amenable to surgical correction. Therefore, it is essential to make
      an accurate diagnosis to offer an adequate treatment. In this article, we review
      the common congenital and acquired uterine anomalies associated with recurrent
      pregnancy losses, and discuss contemporary diagnosis and treatment options.

PMID- 16418976
TI  - Endocrinology of recurrent pregnancy loss.
AB  - Following implantation, the maintenance of the pregnancy is dependent on a
      multitude of endocrinological events that will eventually aid in the successful
      growth and development of the fetus. Although the great majority of pregnant
      women have no pre-existing endocrine abnormalities, a small number of women can
      have certain endocrine alterations that could potentially lead to recurrent
      pregnancy losses. It is estimated that approximately 8 to 12% of all pregnancy
      losses are the result of endocrine factors. During the preimplantation period,
      the uterus undergoes important developmental changes stimulated by estrogen, and
      more importantly, progesterone. Progesterone is essential for the successful
      implantation and maintenance of pregnancy. Therefore, disorders related to
      inadequate progesterone secretion by the corpus luteum are likely to affect the
      outcome of the pregnancy. Luteal phase deficiency, hyperprolactinemia, and
      polycystic ovarian syndrome are some examples. Several other endocrinological
      abnormalities such as thyroid disease, hypoparathyroidism, uncontrolled diabetes,
      and decreased ovarian reserve have been implicated as etiologic factors for
      recurrent pregnancy loss.

PMID- 16418977
TI  - Obstetrical antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease manifested by a
      thrombotic or obstetrical event in the presence of antiphospholipid antibodies.
      Obstetrical APS was initially described in the 1950s. Obstetrical features
      presently include recurrent pre-embryonic and embryonic miscarriage, fetal
      demise, preeclampsia, intrauterine growth restriction, and possibly placental
      abruption. Since the first description of obstetrical APS, researchers have
      unraveled some of the pathophysiology involved in the disease. At present, there
      are numerous antiphospholipid antibodies that can be measured in human serum,
      each of which requires evaluation with regard to whether an association with
      obstetrical events exists. Clinical trials have provided some insight into
      optimal treatment protocols, but to date, such trials are limited. On the basis
      of small, randomized trials, live birth rates of approximately 70 to 80% have
      been reported with the use of low-dose acetylsalicylic acid and heparin. Despite
      such encouraging results, ongoing pregnancies are fraught with maternal and fetal
      morbidity. This review will highlight the obstetrical morbidity associated with
      APS, discuss the limitations of the present criteria for diagnosis, appraise
      published treatment trials, and summarize directions for future study of
      obstetrical APS.

PMID- 16418978
TI  - Thrombophilias and recurrent pregnancy loss.
AB  - Thrombophilia by definition represents acquired and/or genetic conditions that
      predispose patients to both venous and arterial thromboembolic events. Thrombosis
      is the most common cause of death worldwide. On the arterial side, myocardial
      infarction and stroke result in significant morbidity and mortality. Venous
      thromboembolic events most commonly involve the deep veins of the lower extremity
      with potential complications of pulmonary emboli. Pregnancy is a hypercoagulable
      state, and thromboembolism is the leading cause of antepartum and postpartum
      maternal mortality. With the description by Dahlback in 1993 of a condition
      initially labeled activated protein C resistance, significant advances have
      rapidly followed. Activated protein C resistance was linked to an underlying
      point mutation resulting in coagulation factor V (factor V Leiden). Recent
      attention has focused on certain inherited thrombophilic factors that may
      predispose to arterial and/or venous thromboses and their possible association
      with pregnancy complications, including early pregnancy loss. These include a
      group of mostly autosomal dominant, inherited gene mutations leading to a
      hypercoagulable state, such as factor V Leiden G1691A, factor II or prothrombin
      G20210A, and hyperhomocysteinemia associated with methylenetetrahydrofolate
      reductase C677T mutation. In addition, deficiencies in protein S, protein C, and
      antithrombin can lead to a hypercoagulable state. Although some studies of
      recurrent pregnancy loss patients with a positive test for an inherited
      thrombophilia are conflicting, a case-control study of untreated recurrent
      miscarriage patients who were heterozygous for the factor V Leiden mutation
      revealed a lower success rate than the controls who had a history of idiopathic
      recurrent miscarriage. With the identification of genetic risk factors, there has
      been synergistic amplification of thrombotic risk when one has an abnormal gene
      (e.g., factor V Leiden) plus environmental issues (e.g., pregnancy). Current
      understanding indicates that a combination of risk factors, including multiple
      inherited thrombophilic defects associated with secondary hypercoagulable states,
      have a particularly strong association with adverse pregnancy outcome.

PMID- 16418979
TI  - Lost in translation.

PMID- 16418980
TI  - Preventing catheter-associated bloodstream infections: a survey of policies for
      insertion and care of central venous catheters from hospitals in the prevention
      epicenter program.
AB  - OBJECTIVE: To determine the extent to which evidence-based practices for the
      prevention of central venous catheter (CVC)-associated bloodstream infections are
      incorporated into the policies and practices of academic intensive care units
      (ICUs) in the United States and to determine variations in the policies on CVC
      insertion, use, and care. DESIGN: A 9-page written survey of practices and
      policies for nontunneled CVC insertion and care. SETTING: ICUs in 10 academic
      tertiary-care hospitals. PARTICIPANTS: ICU medical directors and nurse managers.
      RESULTS: Twenty-five ICUs were surveyed (1-6 ICUs per hospital). In 80% of the
      units, 5 separate groups of clinicians inserted 24%-50% of all nontunneled CVCs.
      In 56% of the units, placement of more than two-thirds of nontunneled CVCs was
      performed in a single location in the hospital. Twenty units (80%) had written
      policies for CVC insertion. Twenty-eight percent of units had a policy requiring
      maximal sterile-barrier precautions when CVCs were placed, and 52% of the units
      had formal educational programs with regard to CVC insertion. Eighty percent of
      the units had a policy requiring staff to perform hand hygiene before inserting
      CVCs, but only 36% and 60% of the units required hand hygiene before accessing a
      CVC and treating the exit site, respectively. CONCLUSION: ICU policy regarding
      the insertion and care of CVCs varies considerably from hospital to hospital.
      ICUs may be able to improve patient outcome if evidence-based guidelines for CVC
      insertion and care are implemented.

PMID- 16418981
TI  - Comparing bloodstream infection rates: the effect of indicator specifications in
      the evaluation of processes and indicators in infection control (EPIC) study.
AB  - OBJECTIVE: Bloodstream infection (BSI) rates are used as comparative clinical
      performance indicators; however, variations in definitions and data-collection
      approaches make it difficult to compare and interpret rates. To determine the
      extent to which variation in indicator specifications affected infection rates
      and hospital performance rankings, we compared absolute rates and relative
      rankings of hospitals across 5 BSI indicators. DESIGN: Multicenter observational
      study. BSI rate specifications varied by data source (clinical data,
      administrative data, or both), scope (hospital wide or intensive care unit
      specific), and inclusion/exclusion criteria. As appropriate, hospital-specific
      infection rates and rankings were calculated by processing data from each site
      according to 2-5 different specifications. SETTING: A total of 28 hospitals
      participating in the EPIC study. PARTICIPANTS: Hospitals submitted deidentified
      information about all patients with BSIs from January through September 1999.
      RESULTS: Median BSI rates for 2 indicators based on intensive care unit
      surveillance data ranged from 2.23 to 2.91 BSIs per 1000 central-line days. In
      contrast, median rates for indicators based on administrative data varied from
      0.046 to 7.03 BSIs per 100 patients. Hospital-specific rates and rankings varied
      substantially as different specifications were applied; the rates of 8 of 10
      hospitals were both greater than and less than the mean. Correlations of hospital
      rankings among indicator pairs were generally low (rs=0-0.45), except when both
      indicators were based on intensive care unit surveillance (rs = 0.83).
      CONCLUSIONS: Although BSI rates seem to be a logical indicator of clinical
      performance, the use of various indicator specifications can produce remarkably
      different judgments of absolute and relative performance for a given hospital.
      Recent national initiatives continue to mix methods for specifying BSI rates;
      this practice is likely to limit the usefulness of such information for comparing
      and improving performance.

PMID- 16418982
TI  - Disinfection of needleless catheter connectors and access ports with alcohol may
      not prevent microbial entry: the promise of a novel antiseptic-barrier cap.
AB  - BACKGROUND: Needleless valve connectors for vascular catheters are widely used
      throughout the United States because they reduce the risk of biohazardous
      injuries from needlesticks and exposure to bloodborne pathogens, such as human
      immunodeficiency virus and hepatitis C virus. Patients with long-term central
      venous catheters are at significant risk of acquiring catheter-related
      bloodstream infections caused by microbes that gain access through the connection
      between the administration set and the catheter or an injection port. Most
      healthcare practitioners wipe the membranous septum of the needleless connector
      or the injection port with 70% alcohol before accessing it. We report a
      simulation study of the efficacy of conventional alcohol disinfection before
      access, compared with that of a novel antiseptic-barrier cap that, when threaded
      onto a needleless luer-activated valved connector, allows a chlorhexidine
      impregnated sponge to come into continuous contact with the membranous surface;
      after removal of the cap, there is no need to disinfect the surface with alcohol
      before accessing it. METHODS: One hundred five commercial, needleless luer
      activated valved connectors, each accessible by a blunt male-connector luer-lock
      attachment, were purchased from 3 manufacturers and were tested. The membranous
      septum of each test device was first heavily contaminated with approximately
      10(5) colony-forming units of Enterococcus faecalis and then was allowed to dry
      for 24 hours. Fifteen of the contaminated devices were not disinfected (positive
      controls), 30 were conventionally disinfected with a commercial 70% alcohol
      pledget, and 60 had the antiseptic cap threaded onto the connector and then
      removed after 10 minutes. The test connectors were then accessed with a sterile
      syringe containing nutrient broth media, which was injected, captured on the
      downstream side of the intraluminal fluid pathway, and cultured quantitatively.
      RESULTS: All 15 control connectors (100%) showed massive transmission of
      microorganisms across the membranous septum (4,500-10,000 colony-forming units).
      Of the 30 connectors accessed after conventional disinfection with 70% alcohol,
      20 (67%) showed transmission of microorganisms (442-25,000 colony-forming units).
      In contrast, of the 60 connectors cultured after application of the novel
      antiseptic cap, only 1 (1.6%) showed any transmission of microorganisms (P <
      .001). CONCLUSIONS: The findings of this study show that, if the membranous
      septum of a needleless luer-activated connector is heavily contaminated,
      conventional disinfection with 70% alcohol does not reliably prevent entry of
      microorganisms. In contrast, the antiseptic-barrier cap provided a high level of
      protection, even in the presence of very heavy contamination. This novel
      technology deserves to be studied in a clinical trial.

PMID- 16418983
TI  - Risk factors and outcomes associated with non-Enterococcus faecalis, non
      Enterococcus faecium enterococcal bacteremia.
AB  - OBJECTIVES: To compare risk factors, clinical features, and outcomes in patients
      with Enterococcus avium, Enterococcus casseliflavus, Enterococcus durans,
      Enterococcus gallinarum, and Enterococcus mundtii bacteremia (cases) with those
      in patients with Enterococcus faecalis bacteremia (controls). DESIGN: A
      retrospective case-control study. SETTING: A 725-bed, university-affiliated,
      academic medical center. PATIENTS: The clinical microbiology database at
      Northwestern Memorial Hospital from January 1994 to May 2003 was searched to
      identify cases; each case was matched to one control on the basis of date of
      admission. RESULTS: Thirty-three cases were identified and matched with 33
      controls. The mean duration of hospital stay was longer (29.7 vs 17.2 days; P =
      .03) and the mean time to acquisition of bacteremia was greater (16.5 vs 6.3
      days; P = .003) for cases than controls. Cases were more likely to have
      underlying hematologic malignancies (P < .001), to have been treated with
      corticosteroids (P = .02), and to be neutropenic (P = .003). Controls were more
      likely to have an indwelling bladder catheter (P = .01), and cases were more
      likely to have the gastrointestinal tract as a source of infection (P = .007) and
      to have concurrent cholangitis (P = .002). There were no differences in severity
      of illness or in mortality rates. CONCLUSIONS: Compared with patients with E.
      faecalis bacteremia, patients with non-E. faecalis, non-Enterococcus faecium
      enterococcal bacteremia were more likely to have a hematologic malignancy, prior
      treatment with corticosteroids, neutropenia, and cholangitis; longer duration of
      hospital stay was also identified as a clinical feature. However, non-E.
      faecalis, non-E. faecium species are not associated with any differences in
      mortality.

PMID- 16418984
TI  - Risk factors for groin wound infection after femoral artery catheterization: a
      case-control study.
AB  - OBJECTIVE: Groin wound infection (GWI) after femoral artery catheterization is
      unusual. However, several reports of GWI associated with the use of a Perclose
      device appear in the surgical literature. DESIGN: A case-control study. SETTING:
      We pooled 23 cases and 83 controls from a university hospital and a community
      medical center. PATIENTS: A case was defined as a patient who developed a GWI
      after a femoral artery catheterization. At the university hospital, 3 controls
      were randomly selected from the at-risk population and matched to each case by
      time of procedure only (within 2 weeks). At the community medical center, 4
      controls were selected and matched to each case by time of procedure (within 2
      weeks), sex, and age (within 5 years). RESULTS: We considered several covariates,
      including age, sex, body mass index, medical conditions, Perclose use, hematoma
      formation, and antithrombotic therapy. In a multivariate model, only hematoma
      formation (odds ratio, 68.8; 95% confidence interval, 12.1-391.4) and
      glycoprotein IIb/IIIa platelet inhibitor therapy (odds ratio, 6.1; 95% confidence
      interval, 1.1-33.6) were statistically significant predictors of GWI; Perclose
      use (odds ratio, 0.9; 95% confidence interval, 0.2-3.7) was not a statistically
      significant predictor of GWI. However, most of the hematomas (15/17) formed after
      procedures during which a Perclose device was used. CONCLUSION: Perclose use did
      not have any additional effect on GWI risk beyond the effect that hematoma
      formation had.

PMID- 16418985
TI  - A prospective trial of a novel, silicone-based, silver-coated foley catheter for
      the prevention of nosocomial urinary tract infections.
AB  - OBJECTIVE: To evaluate the efficacy of silicone-based, silver ion-impregnated
      urinary catheters in the prevention of nosocomial urinary tract infections
      (NUTIs). DESIGN: Prospective, crossover study to compare the efficacy of a
      silicone-based, hydrogel-coated, silver-impregnated Foley catheter with that of a
      silicone-based, hydrogel-coated catheter in the prevention of NUTIs. SETTING:
      Adult medical and surgical wards of a university teaching hospital. RESULTS: A
      total of 3,036 patients with catheters were evaluated; 1,165 (38%) of the
      catheters were silver impregnated, and 1,871 (62%) were not silver impregnated.
      Study groups were not identical; there were more men, a shorter duration of
      catheterization, and fewer urine cultures per 1,000 catheter-days in the silver
      catheter group. The rate of NUTIs per 1,000 Foley-days was 14.29 in the silver
      catheter group, compared with 16.15 in the nonsilver catheter group (incidence
      rate ratio, 0.88; 95% confidence interval, 0.70-1.11; P = .29). The median length
      of catheterization prior to the onset of a urinary tract infection (ie, exposure
      time) was 4 days for each group. There were no differences in the recovery of
      gram-positive, gram-negative, or fungal organisms in NUTIs. In a multivariate
      survival analysis, no factors, including silver catheters, were protective
      against NUTI. CONCLUSIONS: Unlike previous trials of latex-based, silver ion
      impregnated Foley catheters, we found that silicone-based, silver-impregnated
      Foley catheters were not effective in preventing NUTIs; however, this study was
      affected by differences in the study groups. Prospective trials remain important
      in assessing the efficacy and cost-effectiveness of new silver-coated products.

PMID- 16418986
TI  - Fungal contamination in hospital environments.
AB  - OBJECTIVES: To assess the degree of fungal contamination in hospital environments
      and to evaluate the ability of air conditioning systems to reduce such
      contamination. METHODS: We monitored airborne microbial concentrations in various
      environments in 10 hospitals equipped with air conditioning. Sampling was
      performed with a portable Surface Air System impactor with replicate organism
      detection and counting plates containing a fungus-selective medium. The total
      fungal concentration was determined 72-120 hours after sampling. The genera most
      involved in infection were identified by macroscopic and microscopic observation.
      RESULTS: The mean concentration of airborne fungi in the set of environments
      examined was 19 +/- 19 colony-forming units (cfu) per cubic meter. Analysis of
      the fungal concentration in the different types of environments revealed
      different levels of contamination: the lowest mean values (12 +/- 14 cfu/m(3))
      were recorded in operating theaters, and the highest (45 +/- 37 cfu/m(3)) were
      recorded in kitchens. Analyses revealed statistically significant differences
      between median values for the various environments. The fungal genus most
      commonly encountered was Penicillium, which, in kitchens, displayed the highest
      mean airborne concentration (8 +/- 2.4 cfu/m(3)). The percentage (35%) of
      Aspergillus documented in the wards was higher than that in any of the other
      environments monitored. CONCLUSIONS: The fungal concentrations recorded in the
      present study are comparable to those recorded in other studies conducted in
      hospital environments and are considerably lower than those seen in other indoor
      environments that are not air conditioned. These findings demonstrate the
      effectiveness of air-handling systems in reducing fungal contamination.

PMID- 16418987
TI  - Knowledge about HIV infection and attitude of nursing staff toward patients with
      AIDS in Iran.
AB  - BACKGROUND: Although adequate knowledge about HIV infection and effective
      antitransmission measures, such as taking universal precautions in the handling
      of blood and other body fluids, are important factors in minimizing the risk of
      HIV transmission in the healthcare setting, little has been reported on the
      knowledge of nurses with regard to HIV infection and their attitude toward
      patients with AIDS in Iran. The aim of the present study was to assess these
      matters. METHODS: A questionnaire-based cross-sectional study was conducted from
      March to April 2003. Included were 1098 nursing staff (registered nurses,
      registered midwives, and auxiliary nurses) from 8 university teaching hospitals
      affiliated with the Shiraz University of Medical Sciences. RESULTS: Registered
      nurses and midwives had a significantly higher level of knowledge about HIV
      infection than did auxiliary nurses (chi(2) = 16.4; df = 1; P < .001). With
      regard to the causative agent of AIDS, nurses holding a bachelor of science in
      nursing or a master of science in nursing (MSN) had a significantly higher level
      of knowledge than did auxiliary nurses (chi(2) = 18.6; df = 1; P < .001). Women
      more often answered correctly that it is not possible to identify HIV-infected
      patients by their appearance during the early stages of disease than did men
      (chi(2) = 17.52; df = 1; P < .001). Although 50.7% of respondents had previously
      cared for patients with AIDS and 54.3% had participated in education programs on
      AIDS, nearly half stated that they would not want to have to care for patients
      with AIDS and that, if assigned to care for such a patient, they would ask to be
      assigned elsewhere. CONCLUSIONS: Our finding that those who scored best on the
      questionnaire were midwives and single female nurses holding an MSN who had
      previously cared for HIV-infected patients scored best might indicate that use of
      selective education campaigns is the most suitable education strategy. The
      effectiveness of targeted education programs on HIV/AIDS should be repeatedly
      evaluated in the future.

PMID- 16418988
TI  - Nosocomial infection surveillance in a surgical intensive care unit in Spain,
      1996-2000: a time-trend analysis.
AB  - OBJECTIVE: To establish the occurrence, distribution, and secular time trend of
      nosocomial infections (NIs) in a surgical intensive care unit (ICU). DESIGN AND
      SETTING: Follow-up study in a teaching hospital in Spain. METHODS: In May 1995 we
      established an nosocomial infection surveillance system in our surgical ICU. We
      collected information daily for all patients who were in the ICU for at least 48
      hours (546 patients from 1996 through 2000). We used the Centers for Disease
      Control and Prevention definitions and criteria for infections. Monthly, we
      determined the site-specific incidence densities of NIs, the rates of medical
      device use, and the Poisson probability distribution, which determined whether
      the case count equalled the number of expected cases (the mean number of cases
      during the previous year, with extreme values excluded). We compared yearly and
      monthly infection rates by Poisson regression, using site-specific NIs as a
      dependent variable and year and month as dummy variables. We tested annual trends
      with an alternative Poisson regression model fitting a single linear trend.
      RESULTS: The average rate of catheter-associated urinary tract infections was 8.4
      per 1000 catheter-days; that of ventilator-associated pneumonia, 21 per 1000
      ventilator-days; and that of central line-associated bloodstream infections, 30
      per 1000 central line-days. The rate of urinary tract infections did not change
      over the study period, but there was a trend toward decreases in the rates of
      central line-associated bloodstream infections and ventilator-associated
      pneumonia. CONCLUSION: An NI surveillance and control program contributed to a
      progressive decrease in NI rates.

PMID- 16418989
TI  - Impact of an infection control program in an intensive care unit in France.
AB  - OBJECTIVE: To evaluate the impact of an infection control program in an intensive
      care unit (ICU). DESIGN: Prospective before-after study. Two 6-month study
      periods were compared; between these periods, an infection control program based
      on isolation was implemented. SETTING: Polyvalent ICU of Montpellier Teaching
      Hospital.Patients. Any patient who was hospitalized in the ICU for >48 hours and
      was discharged during 1 of the 2 periods. MAIN OUTCOME MEASURES: The main patient
      related variables were sex, age at admission, type of patient (surgical, medical,
      or trauma), Simplified Acute Physiology Score II, length of ICU stay, need for
      intubation, duration of exposure to invasive devices, onset of nosocomial
      infection and pathogens responsible, and death. We compared the 2 study periods
      with respect to the incidence of 4 nosocomial infections (pneumonia, urinary
      tract infection, bacteremia, and catheter-associated infection), the frequency of
      infection with the main multidrug-resistant pathogens, and patient survival.
      RESULTS: Patients in periods 1 and 2 were similar with regard to sex, age,
      physiology score, and exposure to invasive devices. The rates of infection with
      multidrug-resistant pathogens were significantly lower during period 2 than
      during period 1 (infection rate: 28.1% of patients in period 1 and 9.6% of
      patients in period 2 [P = .01]; pneumonia rate: 32.6% of patients in period 1 and
      4.2% of patients in period 2 [P = .008]). The mortality rate among patients with
      nosocomial pneumonia was 38.2% in period 1 and 4.3% in period 2 (P = .009).
      CONCLUSIONS: After implementation of an infection control program, the rate of
      infection with multidrug-resistant pathogens decreased, as did the mortality rate
      among patients with nosocomial pneumonia.

PMID- 16418990
TI  - Increased catheter-related bloodstream infection rates after the introduction of
      a new mechanical valve intravenous access port.
AB  - The technology of intravenous catheter access ports has evolved from open ports
      covered by removable caps to more-sophisticated, closed versions containing
      mechanical valves. We report a significant increase in catheter-related
      bloodstream infections after the introduction of a new needle-free positive
      pressure mechanical valve intravenous access port at our institution.

PMID- 16418991
TI  - Determining the significance of coagulase-negative staphylococci identified in
      cultures of paired blood specimens from neonates by species identification and
      strain clonality.
AB  - Of 13 paired coagulase-negative staphylococci (CoNS) isolates recovered from
      cultures of paired blood specimens obtained simultaneously from peripheral sites
      from neonates with clinical sepsis, 12 were identical species with identical
      genotypes. Isolation of CoNS in cultures of 2 blood samples obtained
      simultaneously from separate sites in neonates usually represents true infection.

PMID- 16418992
TI  - Predisposing, reinforcing, and enabling factors influencing influenza vaccination
      acceptance among healthcare workers.
AB  - According to the present case-control study about influenza vaccine acceptance
      among hospital workers, vaccination campaigns should focus mainly on predisposing
      and enabling factors, emphasizing the likelihood of acquiring influenza and the
      positive benefits to patients, addressing concerns about vaccine efficacy or
      safety, and minimizing the time required for the worker to undergo vaccination.

PMID- 16418993
TI  - Increased influenza vaccination of healthcare workers at a pediatric cancer
      hospital: results of a comprehensive influenza vaccination campaign.
AB  - A comprehensive influenza vaccination campaign improved vaccination rates among
      healthcare workers with direct patient care responsibilities from 45% during the
      2003-2004 influenza season to 80% during the 2004-2005 season. A strategy of
      weekly feedback to unvaccinated employees was the most important factor in
      enhancing the rate of vaccination acceptance and was particularly effective among
      the nursing staff.

PMID- 16418994
TI  - An outbreak of Serratia marcescens bloodstream infections associated with misuse
      of drug vials in a surgical ward.
AB  - We report an outbreak of Serratia marcescens bloodstream infection due to
      contamination of total parenteral nutrition solution by insulin or poligeline
      solution when single-use vials were used for multiple doses in a surgical ward.
      Four patients had severe sepsis, and no patient died. Multidose vials, used
      either correctly or incorrectly, may be associated with bloodstream infection.

PMID- 16418995
TI  - Staphylococcus aureus bloodstream infection after cardiac surgery: risk factors
      and outcome.
AB  - Thirty-eight patients (10 cases and 28 controls) were included in a case-control
      study of Staphylococcus aureus bloodstream infection after cardiac surgery in 833
      patients. All bacterial strains were found to be unique by pulsed-field gel
      electrophoresis. In multivariable risk-factor analysis, only valve prosthesis
      implantation was associated with bloodstream infection. The early and late case
      mortality rate was 0%.

PMID- 16418996
TI  - Surgical site infection during hospitalization and after discharge in patients
      who have undergone cardiac surgery.
AB  - During a 13-month period, 513 patients who were scheduled to undergo cardiac
      surgery were prospectively observed for surgical site infection during
      hospitalization after surgery and for 1 month after hospital discharge. Fifty
      three patients showed evidence of surgical site infection (during hospitalization
      for 31 patients and after discharge for 22). Multivariate analysis identified
      that risk factors for surgical site infection differed between infections that
      occurred during hospitalization and those that occurred after discharge.

PMID- 16418997
TI  - Follow-up and management of patients exposed to a flawed automated endoscope
      washer-disinfector in a digestive diseases unit.
AB  - The possible transmission of pathogens to 236 persons exposed to an endoscope
      processed in a flawed automated endoscope washer-disinfector in a
      gastrointestinal endoscopy unit was investigated. During 6 months, 197 patients
      (83.5%) were followed up, and no cases of acute human immunodeficiency virus,
      hepatitis C virus, or hepatitis B virus infection were observed. This event
      created the conditions for improvements in safety procedures.

PMID- 16418998
TI  - An outbreak of pertussis in a hematology-oncology care unit: implications for
      adult vaccination policy.
AB  - A pertussis outbreak in a hematology-oncology care unit involved 10 (8.5%) of 117
      employees. The source was an employee who contracted pertussis via a family
      contact. No screened patients contracted pertussis, likely because of isolation
      measures. Hospitals should consider employee immunization with acellular vaccine
      in healthcare settings where pertussis has high rates of morbidity and mortality.

PMID- 16418999
TI  - Low prevalence of pertussis among children admitted with respiratory symptoms
      during respiratory syncytial virus season.
AB  - Pertussis may go unrecognized during respiratory syncytial virus (RSV) epidemics.
      Nosocomially transmitted pertussis can be severe in infants. Polymerase chain
      reaction (PCR) screening may identify infants with pertussis on admission,
      allowing for preemptive isolation. In a random sample, 1 (0.6%) of 166 children
      admitted to the hospital during RSV season were Bordetella pertussis PCR positive
      during a nonepidemic period. These data show that screening may not be useful
      when pertussis prevalence is low.

PMID- 16419000
TI  - [Non SLE connective tissue diseases: general aspects and kidney].
AB  - Connective tissue diseases represent a group of heterogeneous disorders that
      share certain common features, including inflammation of the skin, joints and
      other structures rich in connective tissue, as well as altered immunoregulation
      patterns, including autoantibody production and cell-mediated immunity
      abnormalities. While certain distinct clinical entities can be defined,
      manifestations can vary considerably from patient to patient, and the overlap of
      clinical features between and among specific diseases is common. Genetic,
      environmental and sex hormonal factors are likely to be of pathogenic importance.
      Among these diseases, systemic lupus erythematosus is the most frequent, followed
      by systemic sclerosis or scleroderma (SSc), Sjogren's disease, polymyositis and
      dermatomyositis and mixed connective tissue disease. Systemic sclerosis involves
      multiple organs in a process consisting of disseminated sclerosis affecting all
      compartments. Prominent vascular lesions typify the renal lesions. Scleroderma
      crisis is a major complication of SSc, characterized by severe hypertension,
      rapidly progressive renal failure, thrombotic microangiopathy with hemolitic
      anemia and low platelet count: the prompt use of angiotensin-converting enzyme
      (ACE) inhibitors significantly increased the 1-yr survival rate from 15 to 76%.
      Sjogren's syndrome is an immunologic disorder characterized by progressive
      lymphocytic destruction of the exocrine gland, frequently resulting in
      symptomatic eye and mouth dryness. The interstitial lesions constitute the
      principal renal manifestations: interstitial infiltrates and small lymphocytes,
      which can be homogenous and massive. In polymyositis and dermatomyositis renal
      involvement is rare.

PMID- 16419002
TI  - [Treatment of lupus nephritis].
AB  - SLE begins with renal symptoms in about 30-50% of the patients and after 10 years
      over 70% of them has complications. In the last years the medical therapy
      improved the outcome of SLE and its complications. Presently, the survival for
      lupus nephritis is 80% after five years. The nephritis treatment is divided into
      remission-inducing treatment that is followed by remission-maintaining treatment.
      Moreover, it is considered the therapy for preventing or reducing toxic and side
      effects from drugs and the therapy for flare-ups. To initiate the specific
      therapy is important to consider the histological class (WHO). In the remission
      inducing treatment steroids are used alone for 3-6 months in class IIB or in
      association with cyclophosphamide in classes III-IV and V and for flare-ups. For
      remission-maintaining treatment steroids are used in association with
      azathioprine. The drugs improved the outcome of nephritis but produced side
      effects that determined the suspension of the drug and/or reduction of dosage
      and/or the use of other drugs like mycophenolate mofetil or rituximab.

PMID- 16419001
TI  - [The clinical immunology laboratory in diagnosis and monitoring of systemic lupus
      erythematosus and connective tissue diseases].
AB  - The laboratory and particularly clinical immunology laboratories have an
      essential role in diagnosing and monitoring systemic lupus erythematosus (SLE),
      as well as other connective tissue diseases. The role of the clinical immunology
      laboratory in these diseases is to confirm or exclude diagnosis, to monitor
      disease activity, and to identify subgroup of patients. To obtain the best
      results in terms of diagnostic performance and clinical usefulness, the following
      recommendations should be fulfilled: anti-nuclear antibodies (ANA) determination
      by indirect immunofluorescence on Hep-2 cells is an effective screening assay in
      patients with clinical features of SLE. A negative ANA test makes the diagnosis
      of SLE unlikely. Anti-dsDNA antibodies are highly specific for SLE and are
      associated with renal involvement. The method of choice for anti-dsDNA is the
      Farr assay; however, the necessity of using radioactive materials reduces its
      applicability. As an alternative, immunofluorescence on Crithidia Luciliae can be
      used in the diagnostic phase due to its high specificity. The detection of
      antibodies to extractable nuclear antigens (ENA) and to phospholipids (lupus
      anticoagulant and anti-cardiolipin antibodies) is useful in identifying subgroups
      of patients at risk for some clinical manifestations. Anti-dsDNA measurement with
      a quantitative assay (the Farr assay or ELISA) is currently the best method to
      monitor disease activity along with complement levels. New assays (anti-C1q and
      anti-nucleosome antibodies) have been recently proposed for the diagnosis (anti
      nucleosome) and monitoring of SLE patients (anti-C1q and anti-nucleosome
      antibodies), with promising results.

PMID- 16419003
TI  - [SLE: Extra-renal clinical manifestations and lupus nephritis].
AB  - Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease
      affecting multiple organ systems, skin and joints the most involved. Lupus
      Nephritis occurs in Approximately 50% of patients, sometimes it may be the first
      manifestation of SLE. Clinical features range from asymptomatic urinary
      abnormalities to full-blown nephrotic syndrome or rapidly progressive renal
      failure. Because of the heterogeneity of clinical renal manifestations, renal
      biopsy plays an important role in the management of patients with SLE: it
      provides information about the class, severity, activity and chronicity of the
      renal disease that cannot be accurately predicted on the basis of clinical
      parameters. The complexity of protean renal manifestation of SLE can be
      approached using the original WHO classification (1982), recently revised (2004).

PMID- 16419004
TI  - [Fabry disease].
AB  - Anderson--Fabry's disease is an hereditary disease with an X-linked genetic
      transmission, caused by the congenital deficiency of the lysosomial enzyme alpha
      galactosidase A. It is a rare disease, but the estimated 1 patient every 117.000
      male population is increasing and this can be demonstrated by simplifying the
      dosage techniques for the enzyme. The clinical picture comes from the
      accumulation of glycosphingolipids in many organs, mainly vessels, heart, nervous
      tissue, kidney and sight. The histological lesion appears as damage to the
      lysosomial membrane with subsequent migration of the lipid corpuscles into the
      cytoplasm and the breakdown of metabolic cellular activities. Prior to the advent
      of enzyme replacement therapy, which is based on the administration of the
      recombinant enzyme, the course of the disease was certainly fatal (early death by
      ictus or ischemic cardiopathy, terminal kidney failure). Despite the positive
      results achieved, information obtained from the present observation research
      should be help to verify the validity of the enzyme replacement therapy.

PMID- 16419005
TI  - [The kidney in dysproteinemia].
AB  - Several renal diseases are associated with the dysproteinemias, and their
      pathogenesis is related to paraprotein deposits in the kidney: light chains can
      affect the kidney by a direct toxic effect on tubular cells, or by intratubular
      or tissue precipitation. Multiple myeloma (MM) is the most prevalent
      dysproteinemia, and the spectrum of associated renal diseases includes myeloma
      kidney (cast nephropathy), amyloidosis and monoclonal immunoglobulin deposition
      disease (MIDD). Renal failure is seen in approximately 50% of patients with MM at
      diagnosis, most frequently attributed to myeloma kidney. Renal function can
      recover in more than half the patients by prompt rehydration with intravenous
      fluids, to achieve a urine flow of >3 l/day, and by treating the hypercalcemia.
      Plasma exchange in combination with corticosteroids is suggested in patients with
      rapidly progressive renal failure. When renal failure is associated with MIDD or
      amyloidosis, renal function recovery is reduced to 10%, and patient survival is
      related to the entity of extrarenal tissue distribution of paraprotein deposits.
      Dialysis should be offered to patients with end-stage renal disease. High dose
      chemotherapy and autologous stem cells transplantion (SCT) is recommended in
      patients who do not have severe co-morbidities.

PMID- 16419006
TI  - [Management of multiple myeloma].
AB  - Multiple myeloma (MM) remains an incurable malignancy, the median overal survival
      of patients receiving conventional chemotherapy being only 36-60 months. MGUS can
      evolve to MM in a percentage of 0.6-3% per year. The therapeutic management of
      multiple myeloma (MM) for the last several decades has mainly involved regimens
      based on use of glucocorticoids and cytotoxic chemotherapeutics. Melphaln and
      Prednisone (MP) are recognized as the classic treatment of MM. In patients
      candidate to bone marrow transplantation, VAD (Vincrisrine, Adriamicin,
      Dexamethasone) regimen is more indicated because it does not cause stem cell
      injury. High dose chemotherapy and and Autologous stem cells transplantation
      represent the best treatment for patients with MM who are younger than 65 years
      and free of severe comorbidities. Thalidomide alone or in combination with
      steroids has significant activity in multiple myeloma (MM). After the role of
      thalidomide in the management of patients with advanced or refractory MM had been
      established, many studies are evaluating the efficacy and toxicity of thalidomide
      as first-line therapy for patients with newly diagnosed disease. Recent studies
      have enhanced our understanding of disease pathogenesis and also provided the
      framework for a new treatment paradigm targeting the MM cell in its bone marrow
      microenvironment to overcome drug resistance and improve patient outcome.
      Clinical trials are confirming the remarkable activity and improved tolerability
      of some of the new agents identified through this paradigm.

PMID- 16419007
TI  - [The renal pathology in light chain deposition disease].
AB  - Light Chain Deposition Disease (LCDD) is a relatively frequent renal disease
      associated with dysproteinemia. Although the light chain deposits can be
      widespread, the kidney is the most frequently involved organ, and renal
      involvement can dominate the clinical condition. The morphological features of
      LCDD can be recognized by light microscopy; however, the diagnosis can be made
      certain only by immunofluorescence microscopy, using antisera to kappa and lambda
      chains, and by electron microscopy.

PMID- 16419008
TI  - [Hemolytic uremic syndrome].
AB  - Hemolytic uremic syndrome (HUS) is a disease characterized by non immune
      hemolytic anemia, low platelet count and renal impairment. In children, the
      disease is most commonly triggered by Shiga-like toxin (Stx)-producing
      Escherichia coli (Stx-E. Coli): however, renal function recovers in up to 70% of
      patients. Plasma infusion or exchange reduces mortality and the risk of end-stage
      renal disease (ESRD) in adult patients. Non-Shiga toxin-associated HUS (non-Stx
      HUS), accounting for only 5-10% of all disease cases, can be sporadic or
      familial. Collectively, non-Stx-HUS forms have a poor outcome. Up to 50% of cases
      progress to ESRD or have irreversible brain damage, and 25% can die during the
      acute phase of the disease. Genetic studies have recently documented that the
      familial form is associated with genetic abnormalities of complement regulatory
      proteins, and evidence is now emerging that similar genetic alterations can
      predispose to sporadic cases of non-Stx-HUS as well. Mutations of genes encoding
      for factor H, a glycoprotein that plays an important role in the regulation of
      the alternative pathway of complement and for MCP, a widely expressed
      transmembrane glycoprotein with an inhibitory role of activated C3, are reported
      in familial HUS. These mutations are more likely to predispose rather than to
      cause the disease directly.

PMID- 16419009
TI  - [Evolution of the classification of acute and chronic transplant rejection].
AB  - In the last twenty years, several systems have been proposed to codify renal
      allograft rejection. The Banff classification for kidney allograft pathology,
      introduced in 1993, started a new era in the standardization of criteria for
      rejection and for allowing uniform reporting. This consensus on allograft grading
      proposed a scheme to guide therapy in transplant patients and to help establish
      an objective rejection end point in clinical trials. This scheme, modified during
      1993-1997 to address many of the criticisms, was substantially improved. Another
      important system of classification of allograft renal biopsies was the
      Cooperative Clinical Trials in Transplantation (CCTT) classification which was
      published in 1997. The aim of this system was to develop a schema that would be
      practical to implement, easy to describe to unfamiliar personnel, reproducible,
      with high rates of sensitivity and specificity and clinically informative
      (predictive of course and/or response to therapy). In March 1997, a fundamental
      revision of the Banff classification for acute rejection was achieved by a
      consensus conference for incorporating many of the strengths of the CCTT system.
      Some of these were the importance of vascular damage (endoarteritis, endothelial
      activation, fibrinoid necrosis) and interstitial hemorrhage, but not the
      interstitial infiltrate or tubulitis, which correlated with response to anti
      rejection therapy and/or 1 year clinical outcome. The most recent modification
      concerns the addition of C4d-positive acute humoral rejection and the emphasis on
      differences between cell-mediated and antibody-mediated rejections. Future
      refinements of these classifications and findings of new molecular markers of
      allograft rejection, such as fas-ligand or granzyme-B, will help to improve
      diagnosis and therapy in renal transplant patients.

PMID- 16419010
TI  - [Immunopathology of acute rejection].
AB  - Acute transplant rejection may be the result of two immunologic mechanisms, T
      cell-mediated and antibody-mediated processes, acting alone or together. Cell
      mediated rejection occurs as T cells react to donor alloantigens which are
      expressed in context of MHC. The major forms of cellular rejection may affect
      tubulo-interstitium, arteries and glomeruli. The former type is characterized by
      infiltration of the interstitium and tubules with activated T cells. Typically
      less than 50% of the cells are CD3 (T3), while the majority are usually CD8 (T8)
      cells. In the tubulo-interstitial form, lymphocytes migrate from peritubular
      capillaries into the interstitium and into the walls of tubules (tubulitis). The
      arterial form is characterized by the accumulation of lymphocytes and monocytes
      beneath endothelial cells of arteries. Endarteritis is mediated by T cells and
      affected arteries are devoid of antibody or complement deposits. There are two
      distinctive forms of acute antibody-mediated rejection, affecting different
      vascular beds: arterial and peritubular capillary. The arterial form is
      characterized by mural necrosis and inflammation. In contrast, the peritubular
      capillary form may have little or variable morphologic changes; it is diagnosed
      by identifying C4d, a stable breakdown product of complement and an indicator of
      immune complex deposition, in peritubular capillary walls. C4d deposition
      correlates with circulating antidonor antibodies.

PMID- 16419011
TI  - [Immunosuppressive drugs and renal transplantation].
AB  - Although the use of new immunosuppressive drugs, and their combination have
      drastically reduced the incidence of acute rejections, the graft survival is
      unchanged in the last ten years. The immunosuppressive drugs can be divided in
      four classes, according to their different site of molecular action:
      proliferative signal inhibitors, amplification signal inhibitors; STATs
      inhibitors, DNA synthesis inhibitors. Steroids act on immune system through
      several mechanisms. Azathioprine is an anti-metabolite that inhibits de-novo
      synthesis of purins, acting on S-phase of cellular cycle. Mycophenolate-Mofetil
      (MMF) is also an anti-metabolite, purine synthesis inhibitor that, differently
      from azathioprine, acts specifically on IMPDH (Inositolmonophosphate
      dehydrogenasis) through a non-competitive mechanism. Calcineurin inhibitors
      (cyclosporin and tacrolimus) act on amplification of intracellular signal. The
      most important therapeutic side-effect of calcineurin inhibitors is the
      nephrotoxicity. Other inhibitor agents of the amplification signal are monoclonal
      antibodies anti-a chain of IL-2 (CD25). Another drug used in the last years, is
      sirolimus (SRL) or rapamycine, an immunosuppressive agent that act, through the
      inhibition of T lymphocyte activation.

PMID- 16419013
TI  - Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients
      and development of a disease-associated protein chip.
AB  - Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive
      depression of myocardial contractile function and ventricular dilatation. Thirty
      percent of DCM patients belong to the inherited genetic form; the rest may be
      idiopathic, viral, autoimmune, or immune-mediated associated with a viral
      infection. Disturbances in humoral and cellular immunity have been described in
      cases of myocarditis and DCM. A number of autoantibodies against cardiac cell
      proteins have been identified in DCM. In this study, we have profiled the
      autoantibody repertoire of plasma from DCM patients against a human protein array
      consisting of 37,200 redundant, recombinant human proteins and performed
      qualitative and quantitative validation of these putative autoantigens on protein
      microarrays to identify novel putative DCM specific autoantigens. In addition to
      analyzing the whole IgG autoantibody repertoire, we have also analyzed the IgG3
      antibody repertoire in the plasma samples to study the characteristics of IgG3
      subclass antibodies. By combining screening of a protein expression library with
      protein microarray technology, we have detected 26 proteins identified by the IgG
      antibody repertoire and 6 proteins bound by the IgG3 subclass. Several of these
      autoantibodies found in plasma of DCM patients, such as the autoantibody against
      the Kv channel-interacting protein, are associated with heart failure.

PMID- 16419014
TI  - Proteomics in China.

PMID- 16419015
TI  - An alternative strategy for high throughput generation and characterization of
      monoclonal antibodies against human plasma proteins using fractionated native
      proteins as immunogens.
AB  - Construction of a monoclonal antibody (mAb) bank containing a vast variety of
      antibodies against human tissue proteins is important for proteomic research. A
      novel strategy of subtractive immunization using fractionated native proteins was
      developed for high throughput generation of mAb against human plasma proteins. By
      this novel approach, the bottleneck of antigen preparation can be overcome by
      combining repeated immunization of animals with subtracted fractions of plasma or
      tissue proteins and identification of target antigen by immunoprecipitation/mass
      spectrum strategies. Plasma freshly collected from healthy adults was pooled and
      three fractions were prepared by size exclusion chromatography. Mice were
      immunized with the fractionated plasma proteins, and 205 strains of hybridomas
      secreting mAb were obtained after two-round subtractive immunizations and cell
      fusions. In the first round, 110 strains of hybridomas were established, in which
      77 strains secreting mAb were identified against 10 human plasma high-abundant
      proteins. In the second round, plasma fraction I was absorbed with mAb against
      IgM, IgG, ceruloplasmin and haptoglobin. The absorbed fraction I was used as
      immunogen for the second round immunization and cell fusion. Ninety-five strains
      of hybridomas secreting mAb were obtained. Although the target antigens of mAb
      from 82 strains of hybridomas were identified as IgM, IgA, alpha2-macroglobulin
      and fibrinogen, about 85% antibodies obtained from this round were identified as
      new antibodies when compared with mAb obtained in the first round immunization
      with plasma fraction I. The results suggest that subtractive immunization with
      fractionated plasma proteins followed by identification of antigens with
      immunoprecipitation/mass spectrum may be an effective approach for rapid
      preparation of mAb against high-and medium-abundant plasma or tissue proteins.

PMID- 16419016
TI  - Proteomic analysis of high-density lipoprotein.
AB  - Plasma lipoproteins, such as high-density lipoprotein (HDL), can serve as
      carriers for a wide range of proteins that are involved in processes such as
      lipid metabolism, thrombosis, inflammation and atherosclerosis. The
      identification of HDL-associated proteins is essential with regards to
      understanding these processes at the molecular level. In this study, a
      combination of proteomic approaches including 1-DE and 2-DE MALDI-TOF, isotope
      coded affinity tag and Western blot analysis were employed to identify proteins
      associated with human HDL. To minimize potential losses of HDL-associated
      proteins during isolation, a one-step ultracentrifugation technique was applied
      and the quality of purified HDL was confirmed by nephelometry, high-performance
      gel chromatography, and Western blot analysis. MS analysis revealed the presence
      of 56 HDL-associated proteins including all known apolipoproteins and lipid
      transport proteins. Furthermore, proteins involved in hemostasis and thrombosis,
      the immune and complement system were found. In addition, growth factors,
      receptors, hormone-associated proteins and many other proteins were found to be
      associated with HDL. Our approach thus resulted in the identification of a large
      number of proteins associated with HDL. The combination of proteomic technologies
      proved to be a powerful and comprehensive tool for the identification of proteins
      on HDL.

PMID- 16419017
TI  - A new parallel algorithm of MP2 energy calculations.
AB  - A new parallel algorithm has been developed for second-order Moller-Plesset
      perturbation theory (MP2) energy calculations. Its main projected applications
      are for large molecules, for instance, for the calculation of dispersion
      interaction. Tests on a moderate number of processors (2-16) show that the
      program has high CPU and parallel efficiency. Timings are presented for two
      relatively large molecules, taxol (C(47)H(51)NO(14)) and luciferin
      (C(11)H(8)N(2)O(3)S(2)), the former with the 6-31G* and 6-311G** basis sets
      (1,032 and 1,484 basis functions, 164 correlated orbitals), and the latter with
      the aug-cc-pVDZ and aug-cc-pVTZ basis sets (530 and 1,198 basis functions, 46
      correlated orbitals). An MP2 energy calculation on C(130)H(10) (1,970 basis
      functions, 265 correlated orbitals) completed in less than 2 h on 128 processors.

PMID- 16419018
TI  - An algorithm for the uniform sampling of iso-energy surfaces and for the
      calculation of microcanonical averages.
AB  - In this article an algorithm is proposed to efficiently perform the uniform
      sampling of an iso-energy surface corresponding to a fixed potential energy U of
      a molecular system, and for calculating averages of certain quantities over
      microstates having this energy (microcanonical averages). The developed sampling
      technique is based upon the combination of a recently proposed method for
      performing constant potential energy molecular dynamics simulations [Rapallo, A.
      J Chem Phys 2004, 121, 4033] with well-established thermostatting techniques used
      in the framework of standard molecular dynamics simulations, such as the Andersen
      thermostat, and the Nose-Hoover chain thermostat. The proposed strategy leads to
      very accurate and drift-free potential energy conservation during the whole
      sampling process, and, very important, specially when dealing with high
      dimensional or complicated potential functions, it does not require the
      calculation of the potential energy function hessian. The technique proved to be
      very reliable for sampling both low- and high-dimensional surfaces.

PMID- 16419019
TI  - On the reversible O2 binding of the Fe-porphyrin complex.
AB  - Electronic mechanism of the reversible O(2) binding by heme was studied by using
      Density Functional Theory calculations. The ground state of oxyheme was
      calculated to be open singlet state [Fe(S =1/2) + O(2)(S = 1/2)]. The potential
      energy surface for singlet state is associative, while that for triplet state is
      dissociative. Because the ground state of the O(2)+ deoxyheme system is triplet
      in the dissociation limit [Fe(S = 2) + O(2)(S = 1)], the O(2) binding process
      requires relativistic spin-orbit interaction to accomplish the intersystem
      crossing from triplet to singlet states. Owing to the singlet-triplet crossing,
      the activation energies for both O(2) binding and dissociation become moderate,
      and hence reversible. We also found that the deviation of the Fe atom from the
      porphyrin plane is also important reaction coordinate for O(2) binding. The
      potential surface is associative/dissociative when the Fe atom locates in
      plane/out-of-plane.

PMID- 16419020
TI  - Systematic Gaussian basis-set limit using completeness-optimized primitive sets.
      A case for magnetic properties.
AB  - We discuss the connection between the completeness of a basis set, measured by
      the completeness profiles introduced by Chong (Can J Chem 1995, 73, 79) at a
      certain exponent interval, and the possibility of reproducing molecular
      properties that arise either in the region close to the atomic nuclei or in the
      valence region. We present a scheme for generating completeness-optimized
      Gaussian basis sets, in which a preselected range of exponents is covered to an
      arbitrary accuracy. This is done by requiring Gaussian functions, the exponents
      of which are selected without reference to the atomic structure, to span the
      range with completeness profile as close to unity as wanted with as few functions
      as possible. The initial exponent range can be chosen suitable for calculations
      of molecular energetics or other valence-like properties. By extending the
      exponent range, properties requiring augmentation of the basis at a given angular
      momentum value and/or in a given distance range from the nucleus may be
      straightforwardly and systematically treated. In this scheme a universal, element
      independent exponent set is generated in an automated way. The relation of basis
      set completeness and performance in the calculation of magnetizability, nuclear
      magnetic shielding, and spin-spin coupling is tested with the completeness
      optimized primitive sets and literature basis sets.

PMID- 16419021
TI  - Development of a multi-residue method for the determination of 18 carbamates in
      tobacco by high-performance liquid chromatography/positive electrospray
      ionisation tandem mass spectrometry.
AB  - A multi-residue method for the determination of carbamates in tobacco was
      developed by high-performance liquid chromatography (HPLC) triple quadrupole mass
      spectrometry (MS). A rapid sample preparation consisted of an extraction step
      with methanol, centrifugation and 1:1 dilution with aqueous 10 mM ammonium
      acetate. After filtration these extracts were directly analysed by reversed-phase
      HPLC coupled to positive electrospray ionisation tandem mass spectrometry
      operated in the multiple reaction monitoring mode. Capillary voltage and dwell
      times were optimised to reduce matrix effects and to increase sensitivity. The
      method was validated for the determination of 18 carbamates in three main types
      of raw tobacco and three tobacco products. The interday accuracy ranged between
      80 and 110% with a relative standard deviation (RSD) of <30%. The limits of
      quantification (LOQs) ranged between 0.01 and 0.04 ppm for almost all carbamates,
      except aldicarb sulfone, carbofuran, and pebulate, with LOQs between 0.10 and
      0.20 ppm. These LOQs were clearly below the guidance residue levels defined by
      the Agrochemical Advisory Committee of CORESTA, an association of organisations
      having scientific research relative to tobacco.

PMID- 16419022
TI  - Investigation of several unique tandem mass spectrometric fragmentation patterns
      of NFDEIDR, an orcokinin analog, and its N-terminal dimethylated form.
AB  - Orcokinins are a family of myotropic neuropeptides widely present in various
      decapod crustaceans and insect species. The majority of the orcokinins identified
      to date share a conserved sequence of NFDEIDR at their N-termini. Electrospray
      ionization quadrupole time-of-flight tandem mass spectrometric (ESI-QTOF-MS/MS)
      analysis of doubly charged orcokinin precursor ions reveals the presence of a y(n
      - 1) + 10 peak, which is more intense than that for the y(n - 1) ion. To
      elucidate the identity of this novel fragment ion and understand the mechanism
      underlying this fragmentation, we employed a combined approach involving the use
      of isotopic N-terminal dimethylation, methyl esterification, and isotope-encoded
      NFDEIDR. Comparison of the fragmentation patterns of these chemically modified
      orcokinin analogs allowed the determination of the structure of the y(n - 1) + 10
      ion as y(n - 1) + CO--H2O. The yx + CO--H2O ions, along with the yx + CO and yx +
      CO--NH3 ions, are also present in the MS/MS spectra of NFDEIDR and several other
      peptides. Additionally, we report two other unusual fragmentation ions in the
      MS/MS spectra of N-terminal dimethyl NFDEIDR (2+), which yields the novel
      fragment ions of the y(n - 1) + 38 ion and the [M+2H-59]2+ ion. These two ion
      series involve the neutral loss of the asparagine side chain. The same sets of
      ions are also present in other peptides with dimethyl-modified asparagines at the
      N-terminus. The competition between the side-chain loss and loss of dimethylamine
      is described. The loss of the side chain of N-terminal dimethyl Asp1 is reported
      as well. We also report for the first time the neutral loss of ammonia from the N
      terminal amino group of Asn1 and the loss of CO2 from the side chain of aspartic
      acid.

PMID- 16419023
TI  - High-throughput quantification for a drug mixture in rat plasma-a comparison of
      Ultra Performance liquid chromatography/tandem mass spectrometry with high
      performance liquid chromatography/tandem mass spectrometry.
AB  - A quantitative Ultra Performance liquid chromatography/tandem mass spectrometry
      (UPL/MS/MS) protocol was developed for a five-compound mixture in rat plasma. A
      similar high-performance liquid chromatography/tandem mass spectrometry
      (HPLC/MS/MS) quantification protocol was developed for comparison purposes. Among
      the five test compounds, three preferred positive electrospray ionization (ESI)
      and two preferred negative ESI. As a result, both UPLC/MS/MS and HPLC/MS/MS
      analyses were performed by having the mass spectrometer collecting ESI multiple
      reaction monitoring (MRM) data in both positive and negative ion modes during a
      single injection. Peak widths for most standards were 4.8 s for the HPLC analysis
      and 2.4 s for the UPLC analysis. There were 17 to 20 data points obtained for
      each of the LC peaks. Compared with the HPLC/MS/MS method, the UPLC/MS/MS method
      offered 3-fold decrease in retention time, up to 10-fold increase in detected
      peak height, with 2-fold decrease in peak width. Limits of quantification (LOQs)
      for both HPLC and UPLC methods were evaluated. For UPLC/MS/MS analysis, a linear
      range up to four orders of magnitude was obtained with r2 values ranging from
      0.991 to 0.998. The LOQs for the five analytes ranged from 0.08 to 9.85 ng/mL.
      Three levels of quality control (QC) samples were analyzed. For the UPLC/MS/MS
      protocol, the percent relative standard deviation (RSD%) for low QC (2 ng/mL)
      ranged from 3.42 to 8.67% (N = 18). The carryover of the UPLC/MS/MS protocol was
      negligible and the robustness of the UPLC/MS/MS system was evaluated with up to
      963 QC injections.

PMID- 16419024
TI  - Combined use of gas chromatography and selected ion flow tube mass spectrometry
      for absolute trace gas quantification.
AB  - The value of the gas chromatography (GC) and selected ion flow tube mass
      spectrometry (SIFT-MS) combination for the analysis of trace gases is
      demonstrated by the quantification of acetone in air samples using the three
      precursor ions available to SIFT-MS, viz. H3O+, NO+ and O2+, and by the
      separation of the isomers 1-propanol and 2-propanol, and their analysis using
      H3O+ precursor ions. It is shown that the GC/SIFT-MS combination allows for
      accurate trace gas quantification obviating the regular, time-consuming
      calibrations that are usually required for the more commonly used detectors of GC
      systems, and the positive identification of isomers in mixtures that is often
      challenging using SIFT-MS alone. Thus, the GC/SIFT-MS combination paves the way
      to more confident analyses of complex mixtures such as exhaled breath.

PMID- 16419025
TI  - Simple, sensitive and rapid liquid chromatography/atmospheric pressure chemical
      ionization mass spectrometric method for the quantitation of Ranolazine in rat
      plasma.
AB  - A sensitive and specific method using liquid chromatography with atmospheric
      pressure chemical ionization mass spectrometry (LC/APCI-MS) has been developed
      and validated for the identification and quantification of Ranolazine in rat
      plasma. A simple liquid-liquid extraction procedure was followed by injection of
      the extracts onto a C18 column with isocratic elution and detection using a
      single quadrupole mass spectrometer in selected ion monitoring (SIM) mode. The
      method was tested using six different batches of blank plasma. Linearity was
      established for the concentration range 0.02-10.0 microg/mL, with a coefficient
      of determination (r) of 0.9998 and good back-calculated accuracy and precision.
      The intra- and inter-day precision (relative standard deviation (RSD) %) was
      lower than 10%, and accuracy ranged from 85 to 115%. The lower limit of
      quantification was reproducible at 0.01 microg/mL with 20 microL plasma. The
      proposed method enables the unambiguous identification and quantification of
      Ranolazine for pre-clinical and clinical studies.

PMID- 16419026
TI  - Simultaneous determination of ten antihistamine drugs in human plasma using
      pipette tip solid-phase extraction and gas chromatography/mass spectrometry.
AB  - Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine,
      diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine,
      cloperastine and clemastine, have been found to be extractable from human plasma
      samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel
      was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with
      0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH
      8.0). After centrifugation of the mixture, the supernatant fraction was extracted
      to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a
      manual micropipettor. The analytes retained on the C18 phase were then eluted
      with methanol by five repeated aspirating/dispensing cycles. The eluate was
      injected into a gas chromatography (GC) injector without evaporation and
      reconstitution steps, and was detected by a mass spectrometer with selected ion
      monitoring in the positive-ion electron impact mode. The separation of the ten
      drugs from each other and from impurities was generally satisfactory using a DB
      1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of
      the ten antihistamines spiked into plasma were 73.8-105%. The regression
      equations for the ten antihistamines showed excellent linearity with detection
      limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of
      variation for plasma were not greater than 9.9%. The data obtained from
      determination of diphenhydramine and chlorpheniramine in human plasma after oral
      administration of the drugs are also presented.

PMID- 16419029
TI  - The MEK/MAPK pathway is involved in the resistance of breast cancer cells to the
      EGFR tyrosine kinase inhibitor gefitinib.
AB  - We investigated the role of the MEK/MAPK pathway in the sensitivity/resistance of
      breast carcinoma cells to the EGFR tyrosine kinase inhibitor gefitinib (IRESSA).
      We assessed the effects of gefitinib on the growth of three breast cancer cell
      lines that showed high (SK-Br-3; IC50 4 microM), intermediate (MDA-MB-361; IC50
      5.3 microM), and low (MDA-MB-468; IC50 6.8 microM) sensitivity to the drug.
      Although treatment with gefitinib inhibited EGFR activation in the three cell
      lines in a similar fashion, significant reduction of both p42/p44-MAPK and AKT
      phosphorylation was observed in SK-Br-3 and MDA-MB-361, but not in MDA-MB-468
      cells. The growth of MDA-MB-468 cells was significantly inhibited by treatment
      with either the PI3K-inhibitor LY294002 or the MEK-inhibitor PD98059. In
      agreement with these findings, treatment of MDA-MB-468 cells with a combination
      of PD98059 and gefitinib produced a synergistic anti-tumor effect, whereas this
      combination was only additive in SK-Br-3 and MDA-MB-361 cells. The combination of
      gefitinib and PD98059 also produced a significant increase in the levels of
      apoptosis in MDA-MB-468 cells as compared with treatment with a single agent.
      This phenomenon was associated with a profound decrease in MAPK activation,
      reduction of BAD (ser112) phosphorylation and a paradoxical increase in the
      levels of AKT activation. Finally, overexpression of a constitutively activated
      form of p42-MAPK in MCF-10A non-transformed human mammary epithelial cells
      resulted in a two- to three-fold increase in the IC50 to gefitinib. Taken
      together, these data strongly support the role of the MEK/MAPK pathway in the
      resistance to gefitinib, and provide the rationale for novel therapeutic
      approaches based on combinations of signal transduction inhibitors.

PMID- 16419030
TI  - Insulin-like growth factor binding protein (IGFBP)-5 is upregulated during both
      differentiation and apoptosis in primary cultures of mouse mammary epithelial
      cells.
AB  - We have previously demonstrated that insulin-like growth factor binding protein-5
      (IGFBP-5) is upregulated following treatment of the mouse mammary epithelial cell
      line HC11 with lactogenic hormones (dexamethasone, insulin, and prolactin-DIP).
      In addition, we have also shown that IGFBP-5 is upregulated in mammary epithelial
      cells in vivo during involution of the rodent mammary gland. We have, therefore,
      postulated that there may be a dual regulation of IGFBP-5 expression during the
      temporally separated processes of differentiation and apoptosis of mammary
      epithelial cells. To test this hypothesis further, we have used a phenotypically
      differentiated model, which comprises primary cultures of mouse mammary
      epithelial cells grown on a layer of EHS (Engelbreth-Holm-Swarm) extracellular
      matrix. We show that lactogenic hormone treatment (hydrocortisone, insulin, and
      prolactin-HIP) of these cultures induces the upregulation of IGFBP-5 thus
      replicating the results obtained with the HC11 cell line. In addition, following
      the induction of apoptosis in primary cultures of mammary epithelial cells by
      treatment with TGFbeta-3, IGFBP-5 expression is also upregulated. In parallel
      with this upregulation of IGFBP-5, there is also an increase in the levels of
      cleaved caspase-3, a well-characterized marker of cellular apoptosis. These
      findings confirm previous in vivo work demonstrating an increase in IGFBP-5
      expression during involution of the mouse mammary gland. When HC11 cells are
      cultured under serum-free conditions (a well-characterized apoptotic insult in
      cell culture), there is also an increase in cleaved caspase-3 levels.
      Unexpectedly, in the presence of TGFbeta-3, caspase-3 levels are attenuated. In
      the presence of DIP, caspase-3 levels are also decreased in HC11 cells. As
      described previously, TGFbeta-3 inhibits beta-casein synthesis in HC11 cells. In
      the HC11 cell line (in contrast to primary cultures of mammary epithelial cells),
      there is no evidence for TGFbeta-3 induction of IGFBP-5 under either serum-free
      or DIP-supplemented conditions. We believe our data with primary cultures of
      mammary epithelial cells support the hypothesis of dual regulation of IGFBP-5
      expression during both differentiation and apoptosis in the mammary gland and
      emphasizes the importance of using appropriate cell culture models to investigate
      such phenomena in this tissue. We discuss the possible implications of our
      observations in relation to the physiological processes of pregnancy, lactation,
      and involution in the mammary gland and the associated changes in mammary
      epithelial cell function.

PMID- 16419032
TI  - Polymeric sensor materials: toward an alliance of combinatorial and rational
      design tools?
AB  - Increased selectivity, response speed, and sensitivity in the chemical and
      biological determinations of gases and liquids are of great interest. Particular
      attention is paid to polymeric sensor materials, which are applicable to sensors
      exploiting various energy transduction principles, such as radiant, electrical,
      mechanical, and thermal energy. Ideally, numerous functional parameters of sensor
      materials can be tailored to meet specific needs using rational design
      approaches. However, increasing the structural and functional complexity of
      polymeric sensor materials makes it more difficult to predict the desired
      properties. Combinatorial and high-throughput methods have had an impact on all
      areas of research on polymer-based sensor materials including homo- and
      copolymers, formulated materials, polymeric structures with engineered
      morphology, and molecular shape-recognition materials. Herein we report on the
      state-of-the-art, the development trends, and the remaining knowledge gaps in the
      area of combinatorial polymeric sensor materials design.

PMID- 16419031
TI  - In vivo association of CReMM/CHD9 with promoters in osteogenic cells.
AB  - Molecular mechanisms that control cell differentiation involve with chromatin
      remodeling activities. We recently identified Chromatin Related Mesenchymal
      Modulator (CReMM), a CHD protein expressed by mesenchymal cells. In this study,
      we analyzed CReMM expression on RNA and protein levels during embryonic
      development in mouse skeletal tissues. CReMM appears transiently during
      mesenchymal cell differentiation, being detected first in osteoprogenitors and
      declining in mature cells. A novel aspect of the study elaborates on in vivo
      association of CReMM with promoters in cells obtained by laser capture micro
      dissection (LCM) technique from periosteum and endochondreal ossification
      regions. Using chromatin immunoprecipitation (ChIP), we proved that CReMM binds
      to skeletal tissue-specific promoters: CBFA1, biglycan, osteocalcin (OC),
      collagen-II, and myosin in a differential manner. The results imply that CReMM
      selectively interacts with analyzed promoters activated in the tissue at the
      appropriate time of development. The identification of CReMM and its tissue
      distribution and function provides an attractive clue for the study of
      transcriptional regulation of osteogenic cells' maturation.

PMID- 16419034
TI  - Protein kinase C theta co-operates with calcineurin in the activation of slow
      muscle genes in cultured myogenic cells.
AB  - Adult skeletal muscle fibers can be divided into fast and slow twitch subtypes on
      the basis of specific contractile and metabolic properties, and on distinctive
      patterns of muscle gene expression. The calcium, calmodulin-dependent protein
      phosphatase, calcineurin, stimulates slow fiber-specific genes (myoglobin (Mb),
      troponin I slow) in cultured skeletal muscle cells, as well as in transgenic
      mice, through the co-operation of peroxisome-proliferation-activator receptor
      gamma co-activator 1alpha (PGC1alpha) myocyte enhancer factor 2 (MEF2), and
      nuclear factor of activated T cells (NFAT) transcription factors. Specific
      protein kinase C isoforms have been shown to functionally co-operate with
      calcineurin in different cellular models. We investigated whether specific
      protein kinase C isoforms are involved in calcineurin-induced slow skeletal
      muscle gene expression. By pharmacological inhibition or exogenous expression of
      mutant forms, we show that protein kinase C theta (the protein kinase C isoform
      predominantly expressed in skeletal muscle) is required and co-operates with
      calcineurin in the activation of the Mb promoter, as well as in the induction of
      slow isoforms of myosin and troponin I expression, in cultured muscle cells. This
      co-operation acts primarily regulating MEF2 activity, as shown by using reporter
      gene expression driven by the Mb promoter mutated in the specific binding sites.
      MEF2 activity on the Mb promoter is known to be dependent on both PGC1alpha and
      inactivation of histone deacetylases (HDACs) activity. We show in this study that
      protein kinase C theta is required for, even though it does not co-operate in,
      PGC1alpha-dependent Mb activation. Importantly, protein kinase C theta regulates
      the HDAC5 nucleus/cytoplasm location. We conclude that protein kinase C theta
      ensures maximal activation of MEF2, by regulating both MEF2 transcriptional
      complex formation and HDACs nuclear export.

PMID- 16419035
TI  - Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for
      proliferative retinopathies.
AB  - Platelet-derived growth factor-B (PDGF-B) has been implicated in the pathogenesis
      of proliferative retinopathies and other scarring disorders in the eye. In this
      study, we sought to test the therapeutic potential of an aptamer that selectively
      binds PDGF-B, ARC126, and its PEGylated derivative, ARC127. Both ARC126 and
      ARC127 blocked PDGF-B-induced proliferation of cultured fibroblasts with an IC50
      of 4 nM. Pharmacokinetic studies in rabbits showed similar peak vitreous
      concentrations of approximately 110 microM after intravitreous injection of 1 mg
      of either ARC126 or ARC127, but the terminal half-life was longer for ARC127 (98
      versus 43 h). Efficacy was tested in rho/PDGF-B transgenic mice that express PDGF
      B in photoreceptors and develop severe proliferative retinopathy resulting in
      retinal detachment. Compared to eyes injected with 20 microg of scrambled aptamer
      in which five of six developed detachments (three total and two partial), eyes
      injected with ARC126 (no detachment in five of six and one partial detachment),
      or ARC127 (no detachment in six of six) had significantly fewer retinal
      detachments. They also showed a significant reduction in epiretinal membrane
      formation. These data demonstrate that a single intravitreous injection of an
      aptamer that specifically binds PDGF-B is able to significantly reduce epiretinal
      membrane formation and retinal detachment in rho/PDGF-B mice. These striking
      effects in an aggressive model of proliferative retinopathy suggest that ARC126
      and ARC127 should be considered for treatment of diseases in which PDGF-B has
      been implicated, including ischemic retinopathies such as proliferative diabetic
      retinopathy, proliferative vitreoretinopathy (PVR), and choroidal
      neovascularization.

PMID- 16419036
TI  - Development and progression of alopecia in the vitamin D receptor null mouse.
AB  - Humans with selected mutations in the vitamin D receptor (VDR) and mouse models
      lacking VDR develop alopecia. Mice null for the Vdr gene are born with a normal
      coat of hair, but fail to initiate normal hair follicle cycling. In this study,
      we examined the morphology of the hair follicle of the Vdr null mouse during days
      13-22 when the hair follicle normally initiates and completes the first catagen.
      We then explored the possibility that the abnormality in hair follicle cycling
      was associated with abnormal expression of hairless (Hr), a putative
      transcriptional regulator known to regulate hair follicle cycling and recently
      shown to regulate VDR transcriptional activity. Our results demonstrate the
      progressive deterioration of the hair follicle through catagen. Comparable to
      VDR, Hr was found in the basal cells of the epidermis and ORS of the hair
      follicle. However, Hr was also found in the IRS and matrix of the follicle,
      regions with little or no VDR. Hr levels increased during catagen, reaching a
      peak by day 19. Levels of Hr were greater in the Vdr null mice compared to
      wildtype controls, results confirmed by quantitative RT-PCR. We conclude that
      lack of VDR causes disruption of hair follicle structure during the first catagen
      resulting in failure of subsequent hair follicle cycling. These changes are
      associated with increased expression of Hr, suggesting a role for VDR in
      regulating Hr expression. Both Hr and VDR are required for normal hair follicle
      cycling.

PMID- 16419037
TI  - HMGB1 expression and release by bone cells.
AB  - Immune and bone cells are functionally coupled by pro-inflammatory cytokine
      intercellular signaling networks common to both tissues and their crosstalk may
      contribute to the etiologies of some immune-associated bone pathologies. For
      example, the receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin
      (OPG)/receptor activator of NF-kappaB (RANK) signaling axis plays a critical role
      in dendritic cell (DC) function as well as bone remodeling. The expression of
      RANKL by immune cells may contribute to bone loss in periodontitis, arthritis,
      and multiple myeloma. A recent discovery reveals that DCs release the chromatin
      protein high mobility group box 1 (HMGB1) as a potent immunomodulatory cytokine
      mediating the interaction between DCs and T-cells, via HMGB1 binding to the
      membrane receptor for advanced glycation end products (RAGE). To determine
      whether osteoblasts or osteoclasts express and/or release HMGB1 into the bone
      microenvironment, we analyzed tissue, cells, and culture media for the presence
      of this molecule. Our immunohistochemical and immunocytochemical analyses
      demonstrate HMGB1 expression in primary osteoblasts and osteoclasts and that both
      cells express RAGE. HMGB1 is recoverable in the media of primary osteoblast
      cultures and cultures of isolated osteoclast precursors and osteoclasts.
      Parathyroid hormone (PTH), a regulator of bone remodeling, attenuates HMGB1
      release in cultures of primary osteoblasts and MC3T3-E1 osteoblast-like cells but
      augments this release in the rat osteosarcoma cell line UMR 106-01, both
      responses primarily via activation of adenylyl cyclase. PTH-induced HMGB1
      discharge by UMR cells exhibits similar release kinetics as reported for
      activated macrophages. These data confirm the presence of the HMGB1/RAGE
      signaling axis in bone.

PMID- 16419038
TI  - Hexose transporters GLUT1 and GLUT3 are colocalized with hexokinase I in caveolae
      microdomains of rat spermatogenic cells.
AB  - Postmeiotic spermatogenic cells, but not meiotic spermatogenic cells respond
      differentially with glucose-induced changes in [Ca2+]i indicating a differential
      transport of glucose via facilitative hexose transporters (GLUTs) specifically
      distributed in the plasma membrane. Several studies have indicated that plasma
      membrane in mammalian cells is not homogeneously organized, but contains specific
      microdomains known as detergent-resistant membrane domains (DRMDs), lipid rafts
      or caveolae. The association of these domains and GLUTs isoforms has not been
      characterized in spermatogenic cells. We analyzed the expression and function of
      GLUT1 and GLUT3 in isolated spermatocytes and spermatids. The results showed that
      spermatogenic cells express both glucose transporters, with spermatids exhibiting
      a higher affinity glucose transport system. In addition, spermatogenic cells
      express caveolin-1, and glucose transporters colocalize with caveolin-1 in
      caveolin-enriched membrane fractions. Experiments in which the integrity of
      caveolae was disrupted by pretreatment with methyl-beta-cyclodextrin, indicated
      that the involvement of cholesterol-enriched plasma membrane microdomains were
      involved in the localization of GLUTs and uptake of 2-deoxyglucose. We also
      observed cofractionation of GLUT3 and caveolin-1 in low-buoyant density membranes
      together with their shift to higher densities after methyl-beta-cyclodextrin
      treatment. GLUT1 was found in all fractions isolated. Immunofluorescent studies
      indicated that caveolin-1, GLUT1, and hexokinase I colocalize in spermatocytes
      while caveolin-1, GLUT3, and hexokinase I colocalize in spermatids. These
      findings suggest the presence of hexose transporters in DRMDs, and further
      support a role for intact caveolae or cholesterol-enriched membrane microdomains
      in relation to glucose uptake and glucose phosphorylation. The results would also
      explain the different glucose-induced changes in [Ca2+]i in both cells.

PMID- 16419039
TI  - S100B stimulates myoblast proliferation and inhibits myoblast differentiation by
      independently stimulating ERK1/2 and inhibiting p38 MAPK.
AB  - The Ca2+-modulated protein of the EF-hand type, S100B, was shown to inhibit rat
      L6 myoblast differentiation and myotube formation by interacting with a high
      affinity with an unidentified receptor (Sorci et al., 2003). We show here that
      S100B independently inhibits the MKK6-p38 MAPK pathway and stimulates the Ras-MEK
      ERK1/2 pathway. The inhibitory effect of S100B on p38 MAPK translates into a
      defective induction of the muscle-specific transcription factor myogenin and the
      antiproliferative factor p21(WAF1), while S100B's stimulatory effect on ERK1/2
      results in stimulation of myoblast proliferation via cyclin D1 induction and Rb
      phosphorylation and protection against apoptosis via activation of NF-kappaB
      transcriptional activity. Also, the S100B's effects that are mediated by the Ras
      MEK-ERK1/2 pathway that is, stimulation of proliferation and protection against
      apoptosis, depend on reactive oxygen species production, being inhibited by
      antioxidants, while the S100B inhibitory effect on the MKK6-p38 MAPK pathway is
      not. We propose that S100B might participate in the regulation of myoblast
      differentiation by stimulating myoblast proliferation, protecting myoblasts
      against apoptosis, and modulating myotube formation.

PMID- 16419040
TI  - SOCS-2 interferes with myotube formation and potentiates osteoblast
      differentiation through upregulation of JunB in C2C12 cells.
AB  - Suppressor of cytokine signaling (SOCS)-2 regulates normal postnatal growth and
      its deficiency in mice causes gigantism with increased bone length and
      proportional enlargement in skeletal muscles. Using C2C12 mesenchymal precursor
      cell line as a model, we investigated a possible role of SOCS-2 in the
      differentiation process of mesenchymal precursors. Stable transfection of SOCS-2
      into C2C12 cells resulted in the acceleration of proliferation and survival, and
      inhibition of spontaneous myotube formation. In addition, SOCS-2 potentiated bone
      morphogenic protein (BMP)-induced transdifferentiation of C2C12 cells into
      osteoblast phenotypes. These effects of SOCS-2 on C2C12 cells differed strikingly
      from that of SOCS-1, another member of SOCS family, and its mechanisms were
      evaluated. SOCS-2 did not alter BMP-induced phosphorylation and nuclear
      accumulation of Smad1, nor the expression of inhibitory-Smads mRNA. However, SOCS
      2 enhanced BMP-induced transcriptional activation of the Smad-responsive reporter
      gene, suggesting that the action of SOCS-2 is exerted at the transcriptional
      level. Interestingly, SOCS-2 overexpression in C2C12 cells increased the
      endogenous JunB protein, one of the key transcriptional factors in the control of
      BMP/Smad signaling responsiveness. In addition, the proteasome inhibitor enhanced
      JunB protein expression in C2C12 cells. Moreover, we found that SOCS-2 reduced
      JunB ubiquitination in COS-7 cells. Although SOCS-2 is a modulator of growth
      hormone (GH) signaling, the upregulation of JunB by SOCS-2 did not require GH
      signaling. Taken together, these results suggest that SOCS-2 positively regulates
      endogenous JunB protein expression in C2C12 cells through inhibition of JunB
      destabilization by the ubiquitin-proteasome pathway, and thereby regulates the
      cell fate of mesenchymal precursors.

PMID- 16419043
TI  - H.J.C. "Jeremy" Swan, MD: in memory of his contributions to cardiovascular
      medicine.

PMID- 16419042
TI  - Spatiotemporal gene control by the Cre-ERT2 system in melanocytes.
AB  - The organ-specific and temporal control of gene activation/inactivation is a key
      issue in the understanding of protein function during normal and pathological
      development and during oncogenesis. We generated transgenic mice bearing a
      tamoxifen-dependent Cre recombinase (Tyr::Cre-ERT2) gene expressed under the
      control of a 6.1 kb murine tyrosinase promoter in order to facilitate targeted
      spatiotemporally controlled somatic recombination in melanoblasts/melanocytes.
      Cre-ERT2 production was detected in tissues containing melanocytes. After
      tamoxifen induction at various times during embryogenesis and adulthood in a Cre
      responsive reporter mouse strain, genetic recombination was detected in the
      melanoblasts and melanocytes of the skin. Thus, the Tyr::Cre-ERT2 transgenic mice
      provides a valuable tool for following this cell lineage and for investigating
      gene function in melanocyte development and transformation.

PMID- 16419041
TI  - Response to mechanical strain in an immortalized pre-osteoblast cell is dependent
      on ERK1/2.
AB  - Mechanical strain inhibits osteoclastogenesis by regulating osteoblast functions:
      We have shown that strain inhibits receptor activator of NF-kappaB ligand (RANKL)
      expression and increases endothelial nitric oxide synthase (eNOS) and nitric
      oxide levels through ERK1/2 signaling in primary bone stromal cells. The primary
      stromal culture system, while contributing greatly to understanding of how the
      microenvironment regulates bone remodeling is limited in use for biochemical
      assays and studies of other osteoprogenitor cell responses to mechanical strain:
      Stromal cells proliferate poorly and lose aspects of the strain response after a
      relatively short time in culture. In this study, we used the established mouse
      osteoblast cell line, conditionally immortalized murine calvarial (CIMC-4),
      harvested from mouse calvariae conditionally immortalized by insertion of the
      gene coding for a temperature-sensitive mutant of SV40 large T antigen (TAg) and
      support osteoclastogenesis. Mechanical strain (0.5-2%, 10 cycles per min,
      equibiaxial) caused magnitude-dependent decreases in RANKL expression to less
      than 50% those of unstrained cultures. Overnight strains of 2% also increased
      osterix (OSX) and RUNX2 expression by nearly twofold as measured by RT-PCR.
      Importantly, the ERK1/2 inhibitor, PD98059, completely abrogated the strain
      effects bringing RANKL, OSX, and RUNX2 gene expression completely back to control
      levels. These data indicate that the strain effects on CIMC-4 cells require
      activation of ERK1/2 pathway. Therefore, the CIMC-4 cell line is a useful
      alternative in vitro model which effectively recapitulates aspects of the primary
      stromal cells and adds an extended capacity to study osteoblast control of bone
      remodeling in a mechanically active environment.

PMID- 16419044
TI  - Synapsin I Cre transgene expression in male mice produces germline recombination
      in progeny.
AB  - The cre/LoxP system can produce conditional loss of gene function in specific
      cell types such as neurons. A transgenic mouse line, utilized by multiple
      studies, used the Synapsin I promoter to drive expression of cre (SynCre) to
      achieve neuronal-specific cre expression. Herein we describe that cre expression
      can also be observed in SynCre mice within the testes after being bred into a
      floxed transgenic mouse line. Cre transcript was expressed in testes resulting in
      recombination of the floxed substrate in testes. In the majority of cases,
      progeny of male SynCre mice inherited a germline recombined floxed allele, while
      this was never observed in progeny from female mice carrying the SynCre allele.
      This observation should alert investigators to a potential confound using these
      mice and enables male germ cell "deletor" strategies.

PMID- 16419045
TI  - Quantitative study of salivary secretion in Parkinson's disease.
AB  - We examined basal and reflex salivary flow rate and composition in 46 patients
      with Parkinson's disease (PD), both in off and on conditions, compared to 13 age
      matched controls without underlying disease or treatment affecting autonomic
      function. Whole saliva was collected 12 hours after withdrawal of dopaminergic
      drugs and at the peak of levodopa-induced motor improvement. Twenty-three of the
      46 PD patients had received domperidone a week before the study. Basal salivary
      flow rate was significantly lower in PD patients in the off state compared to
      controls (P<0.005). Levodopa increased salivary flow rate (P<0.05) both in the
      domperidone-pretreated and untreated groups. Citric acid stimulated salivary flow
      rate in both the off and on states in PD patients. This effect was higher in the
      domperidone-pretreated patients. Salivary concentration of sodium, chloride, and
      amylase was higher in PD patients than in controls and was not affected by
      levodopa or domperidone treatment. Levodopa stimulates both basal and reflex
      salivary flow rate in PD. The mechanism appears to be central, as the effect is
      not blocked by domperidone. Domperidone may have a peripheral effect that
      potentiates reflex salivary secretion. Salivary composition is abnormal in PD and
      is not affected by levodopa treatment.

PMID- 16419046
TI  - Role of CNS alpha1-adrenoceptor activity in central fos responses to novelty.
AB  - The present study investigated, by use of fos immunohistochemistry, whether the
      functional activity of alpha(1)-adrenoceptors is elevated during heightened
      behavioral activity in brain regions shown earlier to contain motoric alpha(1)
      receptors. In confirmation, marked c-fos responses that were blocked by an
      alpha(1)-antagonist (prazosin) were found in four of these brain regions
      (secondary motor, cingulate, piriform cortices, and nucleus accumbens) of animals
      exposed to a mildly novel environment (clean cage), which elicits a high degree
      of sustained exploratory activity. Experimental restriction of exploratory
      activity in the novel cage by a small enclosure did not reduce the fos responses
      in these areas, and in fact, enhanced gene expression when carried out in home
      caged animals suggesting that the fos response may be more closely associated
      with the motivation to be active rather than activity itself. Experiments with
      locally administered alpha(1)-agonists and antagonists in the cortex by reverse
      dialysis showed that the above mentioned alpha(1)-dependent-fos responses were
      the result of activation of local alpha(1)-receptors in these brain regions.
      Unlike the aforementioned brain regions, the fos response of the locus coeruleus
      was not blocked by prazosin, and this nucleus also showed a marked fos increase
      to prazosin itself possibly as a compensatory response to the blockade of
      forebrain alpha(1)-receptors.

PMID- 16419047
TI  - Evaluation of ingredient concentration in powders using two-speed photon
      migration theory and measurements.
AB  - Two-speed photon migration in densely packed powder blends wherein the particle
      diameters are much larger than the incident wavelength are simulated with (i)
      dynamic simulation of particle sedimentation for generating powder structure,
      (ii) the complete-random-mixture model for predicting the active pharmaceutical
      ingredient (API) distribution within the powder bed, and (iii) Monte Carlo for
      tracking the photon trajectories. The simulation results reveal that while both
      absorption and isotropic scattering coefficients increase with solid-volume
      fraction ranging from 0.12 to 0.64, the absorption-to-isotropic-scattering ratio
      is (i) independent of the solid-volume fraction for particle refractive index
      ranging from 1.2 to 1.8 and (ii) linearly dependent upon the API volume
      concentration ranging from 0% to 5%. Frequency domain photon migration
      measurements of resin powder beds of varying particle size verified the developed
      simulation method. Measurements of lactose powder beds of varying particle size,
      solid-volume fraction, and ferric oxide particles content verified the simulation
      results that evidence independence of the absorption-to-isotropic-scattering
      ratio upon solid-volume fraction.

PMID- 16419048
TI  - Investigation of targeting mechanism of new dextran-peptide-methotrexate
      conjugates using biodistribution study in matrix-metalloproteinase-overexpressing
      tumor xenograft model.
AB  - We conducted a biodistribution study in HT-1080 bearing mice to investigate the
      drug targeting mechanism and the cause of side effects of the new dextran-peptide
      methotrexate conjugates. HT-1080 is a human fibrosarcoma cell line that is known
      to overexpress matrix-metalloproteinases (MMPs). The experiments compared
      conjugates carrying MMP sensitive peptide linkers, conjugates carrying MMP
      insensitive linkers, and free methotrexate. Passive targeting was evidenced by
      the prolonged plasma circulation and higher tissue accumulations of both types of
      the conjugates compared to free methotrexate. Independent of the peptide sequence
      of the linker, the ratio of drug accumulation at the tumor versus drug
      accumulation at the major site of side effects (small intestine) for either
      conjugate was increased by the effect of enhance permeation and retention (EPR).
      The conjugate released a sufficient amount of peptidyl methotrexate to cause
      inhibition of tumor growth. There was no significant difference in drug
      accumulation at the tumor site between the MMP-sensitive and the MMP-insensitive
      conjugates. We concluded that the tumor targeting effect of the dextran-peptide
      methotrexate conjugate was dominantly due to passive targeting and EPR. The
      difference in the systemic side effects observed for conjugates with different
      linkers could probably be attributed to their varying susceptibility towards
      enzymes in normal tissues.

PMID- 16419049
TI  - Effects of citronellal, a monoterpenoid in Zanthoxyli Fructus, on the intestinal
      absorption of digoxin in vitro and in vivo.
AB  - Complementary and alternative medicines can be applied concomitantly with
      conventional medicines; however, little drug information is available on these
      interactions. Previously, we reported on the inhibitory effects of an extract and
      monoterpenoids (e.g., (R)-(+)-citronellal) contained in citrus herbs on P
      glycoprotein (P-gp) using P-gp-overexpressed LLC-PK1 cells. The objective of the
      present study was to investigate the effects of (R)-(+)-citronellal on P-gp
      mediated transport in the intestinal absorption process in vitro and in vivo.
      Transcellular transport of [(3)H]digoxin across Caco-2 cell monolayers was
      measured in the presence or absence of (R)-(+)-citronellal. (R)-(+)-citronellal
      reduced the basolateral-to-apical transport and efflux ratio for [(3)H]digoxin
      significantly. Serum concentration-time profiles and pharmacokinetic parameters
      of digoxin after intravenous and oral administration were analyzed in rats
      pretreated with oral (R)-(+)-citronellal. The bioavailability of digoxin after
      oral administration decreased significantly to 75.8% of that after intravenous
      administration at the same dose. (R)-(+)-citronellal increased the
      bioavailability of oral digoxin to 99.9% but had no effects on total body
      clearance, volume of distribution, or elimination rate. These findings suggest
      that (R)-(+)-citronellal can increase the bioavailability of oral digoxin based
      on the blockade of P-gp-mediated efflux of digoxin from intestinal epithelia to
      the lumen in the absorption process.

PMID- 16419050
TI  - Electromigration of ions across the skin: determination and prediction of
      transport numbers.
AB  - In iontophoresis, an electric field across the skin induces electromigration of
      exogenously applied and endogenously present ions. The approach can be used to
      improve dramatically drug delivery by elimination of competing co-ions in the
      externally applied formulation, as this maximizes the fraction of current carried
      by (i.e., the transport number of) the drug. In this study, the dependence of the
      transport number on the nature of the ions present at the anode and cathode was
      examined using 12 different combinations of ions (4 cations x 3 anions). Cationic
      transport numbers (t(C+) (o)) were a function of their inherent mobilities and
      depended upon those of the single anion at the cathode; however, t(C+) (o) was
      independent of the counter-ion concentration. The extensive data obtained agreed
      well, furthermore, with a theoretical framework previously developed for this so
      called "single-ion" situation. In addition, there was a strong correlation
      between ionic transport numbers in the skin and those in aqueous solution, which
      are easily estimated from measurements of ionic mobility. It follows that it
      should be possible, from the framework developed here, to establish a predictive
      tool, combining theory with simple experiments, for the optimization of
      iontophoretic drug delivery.

PMID- 16419051
TI  - Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on
      brain targeting.
AB  - The aim of this investigation was to prepare clonazepam microemulsions (CME) for
      rapid drug delivery to the brain to treat acute status epileptic patients and to
      characterize and evaluate the performance of CME in vitro and in vivo in rats.
      The CME were prepared by the titration method and were characterized for globule
      size and size distribution, zeta potential, and drug content. CME was
      radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain
      was studied in Swiss albino rats after intranasal and intravenous
      administrations. Brain scintigraphy imaging in rabbits was also performed to
      ascertain the uptake of the drug into the brain. Pre and postCME formulation
      treated human nasal mucosa was subjected to transmission electron microscopy to
      investigate the mechanism of drug uptake across the nasal mucosa. CME were
      transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential
      of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam
      microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be
      stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour
      (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME
      administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively
      indicating more effective targeting with intranasal administration and best
      targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling
      points up to 8 h following intranasal administration of CMME compared to
      intravenous was found to be twofold higher indicating larger extent of
      distribution of the drug in brain. Rabbit brain scintigraphy also showed higher
      intranasal uptake of the drug into the brain. Transmission electron microscopy
      revealed significant accretion of CMME within interstitial spaces and
      paracellular mode of transport due to stretching of the tight junctions present
      in the nasal mucosa. This investigation demonstrates a more rapid and larger
      extent of transport of clonazepam into the rat brain with intranasal CMME, which
      may prove useful in treating acute status epileptics.

PMID- 16419052
TI  - Preliminary evaluation of polymer-based drug composite microparticle production
      by coacervate desolvation with supercritical carbon dioxide.
AB  - Drug/polymer particles incorporating phenytoin in polyvinylpyrrolidone (PVP) were
      prepared by desolvation of coacervates sprayed through an ultrasonic converging
      diverging nozzle into supercritical (SC) carbon dioxide. The mean diameter of the
      particles produced and the crystallinity of phenytoin in the drug/polymer
      particles were evaluated with an Aerosizer DSP Particle Size Analyzer and powder
      X-ray diffraction, respectively. The drug release properties from the composite
      particles were evaluated using the USP 24 Method 2 rotational paddle method with
      UV detection. Spraying PVP in ethanol solution into SC carbon dioxide did not
      produce particles. However, a PVP coacervate in a mixture of ethanol and hexanes
      had lower viscosity than the solution, and spraying the coacervate into SC carbon
      dioxide through an ultrasonic converging-diverging nozzle produced micron sized
      particles. The use of a coacervate containing phenytoin and PVP likely led to
      increased interaction between drug and polymer and the composite particles
      contained amorphous phenytoin. The drug content in the composite particles
      approached theoretical values. The drug release rates from the composite
      particles produced from the coacervate were faster than those from particles
      produced by conventional SC methods and complete release was observed.

PMID- 16419053
TI  - Difficult retrieval of the EPI Filterwire with a 5 French FR4 coronary catheter
      following carotid stenting.
AB  - Carotid angioplasty and stenting with an embolic protection device is emerging as
      a reasonable alternative to carotid endarterectomy in high-risk patients. The
      deployment and retrieval of these devices, however, can be problematic. We
      describe a case where a 5 Fr FR4 coronary catheter was used to retrieve an EPI
      Filterwire device following carotid stenting.

PMID- 16419054
TI  - Percutaneous edge-to-edge mitral valve repair: 2-year follow-up in the first
      human case.
AB  - We report the first-in-human mitral valve repair using percutaneous technology
      that creates a "surgical-like" edge-to-edge repair. A catheter-delivered clip was
      introduced transseptally from the femoral vein, advanced through the mitral
      orifice, retracted to grasp the leaflets, and detached to create a functional
      double-orifice valve. The patient had an uncomplicated post-procedural course.
      Echocardiography at 1- and 2-years post procedure showed mild mitral
      regurgitation and positive ventricular remodeling. The success of this case
      suggests that percutaneous mitral valve repair may be a feasible therapy for
      certain patients suffering from mitral regurgitation.

PMID- 16419055
TI  - Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new
      partner gene.
AB  - Chromosome rearrangements are found in many acute leukemias. As a result, genes
      at the breakpoints can be disrupted, forming fusion genes. One of the genes
      involved in several chromosome aberrations in hematological malignancies is NUP98
      (11p15). As NUP98 is close to the 11p telomere, small translocations might easily
      be missed. Using a NUP98-specific split-signal fluorescence in situ hybridization
      (FISH) probe combination, we analyzed 84 patients with acute myeloid leukemia
      (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome with either
      normal karyotypes or 11p abnormalities to investigate whether there are
      unidentified 11p15 rearrangements. Neither NUP98 translocations nor deletions
      were identified in cases with normal karyotypes, indicating these aberrations may
      be very rare in this group. However, NUP98 deletions were observed in four cases
      with unbalanced 11p aberrations, indicating that the breakpoint is centromeric of
      NUP98. Rearrangements of NUP98 were identified in two patients, both showing 11p
      abnormalities in the diagnostic karyotype: a t(4;11)(q1?3;p15) with expression of
      the NUP98-RAP1GDS1 fusion product detected in a 60-year-old woman with AML-M0,
      and an add(11)(p15) with a der(21)t(11;21)(p15;p13) observed cytogenetically in a
      1-year-old boy with AML-M7. JARID1A was identified as the fusion partner of NUP98
      using 3' RACE, RT-PCR, and FISH. JARID1A, at 12p13, codes for retinoblastoma
      binding protein 2, a protein implicated in transcriptional regulation. This is
      the first report of JARID1A as a partner gene in leukemia.

PMID- 16419056
TI  - Bone morphogenetic protein 7 is widely overexpressed in primary breast cancer.
AB  - Bone morphogenetic proteins (BMP) make up a family of extracellular signaling
      molecules that play a critical role in vertebrate development and both inhibit
      and stimulate growth in cancer cells. BMP7 was recently identified in our
      genomewide copy number and expression survey as being activated through
      amplification in breast cancer cell lines. In the present study, we further
      explored BMP7 gene copy number and expression changes in 22 breast cancer cell
      lines and 146 primary breast tumors. FISH analysis revealed that BMP7 copy number
      varied greatly from one cell line to another, with three cell lines showing
      extremely high-level amplification. Among primary tumors, BMP7 copy number was
      increased in 16% of the cases. BMP7 mRNA expression was determined in the cell
      lines and in a subset of 44 tumor samples by RT-PCR or quantitative real-time RT
      PCR, respectively. Despite elevated mRNA levels in cancer cells, there was no
      significant association between copy number increase and mRNA expression, even
      though the highest expression was seen in cell lines and tumors with increased
      BMP7 copy number. Most interestingly, immunohistochemical analysis revealed BMP7
      protein staining in all 11 breast cancer cell lines examined and strongly
      elevated BMP7 protein expression in 71.4% of the tumor samples as compared to
      normal mammary epithelium. Our results illustrate the frequent involvement of
      BMP7 alterations in breast cancer and especially highlight overexpression of the
      BMP7 protein in a very large fraction of primary breast tumors, thus suggesting a
      possible functional role for BMP7 in breast cancer development.

PMID- 16419057
TI  - Genomewide array-based comparative genomic hybridization analysis of acute
      promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is typically associated with the t(15;17) that
      generates the PML-RARA fusion protein. Animal models have shown that although the
      fusion protein is necessary, it is insufficient for the development of APL,
      implying that additional mechanisms are responsible for full-blown leukemia. The
      mutation of specific genes has been implicated in leukemogenesis; however,
      alterations in gene copy number have not been well investigated. Here, we applied
      the genomewide array-comparative genomic hybridization technique to 30 APL
      clinical samples and 2 APL cell lines. It was found that (1) approximately half
      the clinical samples (14 of 30 APL cases) had no detectable chromosomal
      imbalances; and (2) the remaining 16 cases, including the cell lines, exhibited
      recurrent chromosomal imbalances, such as loss of 1p36, 2p11, 16p, and 17p, and
      gain of 8p, 8q, and 13q. These results suggest that chromosomal imbalances are
      largely absent in APL, although some nonrandom chromosomal imbalances could be
      linked to the development of APL in a limited number of cases.

PMID- 16419058
TI  - Chromosomal fragile sites FRA3B and FRA16D show correlated expression and
      association with failure of apoptosis in lymphocytes from patients with thyroid
      cancer.
AB  - It has been suggested that common fragile sites (cFSs) are related to cancer
      development. This appears to be the case for FRA3B and FRA16D, localized in two
      tumor-suppressor genes (FHIT and WWOX, respectively) that are altered by
      deletions or loss of heterozygosity (LOH) in many cancers. The features
      responsible for fragility have not yet been identified. Furthermore, it is still
      unclear whether instability at these regions causes chance deletions and loss of
      function of the associated genes, or whether the gene function itself is related
      to the appearance of fragility. In this study, we analyzed cFS expression in
      lymphocytes from 20 healthy or thyroid cancer-affected subjects exposed to
      radiation after the Chernobyl accident. The same cells were examined for
      apoptosis, a principal function of both the FHIT and WWOX genes. Exceptionally
      elevated chromosome fragility was observed, particularly in cancer patients,
      affecting FRA3B, FRA16D, and a cluster of less highly expressed cFSs; levels of
      chromosome fragility were found to be correlated among these cFSs. Interestingly,
      most expressed cFSs were sites of LOH reported for thyroid tumors; moreover,
      cells with the highest fragility also had a reduced ability to undergo apoptosis.
      These findings reveal previously unknown genetic interactions affecting fragile
      loci, suggestive of a shared function inside mitotic cells. Attenuation of
      checkpoint control and apoptosis resistance seem to be the cell phenotypes
      associated with unusual chromosome fragility. We propose that breakage at
      specific cFS could derive from early epigenetic events at loci involved in
      radiation carcinogenesis. This article contains supplementary Material available
      at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 16419059
TI  - Amplification of CDK4 and MDM2 in malignant melanoma.
AB  - Amplification of the 12q13-15 region is a common event in several human tumors
      including liposarcomas, gliomas, and osteosarcomas. We have demonstrated high
      level amplification of 12q14 in a subset of uncultured malignant melanomas (3 of
      53). High-resolution mapping of the amplicon using quantitative PCR revealed a
      bipartite amplicon consisting of a primary 50-kb amplicon centered on CDK4 and a
      secondary amplicon centered on MDM2, without amplification of the intervening 11
      Mb of genomic DNA. Analysis of mRNA and protein levels in melanomas with 12q14
      amplification demonstrated overexpression of target genes CDK4 and MDM2 without
      loss of CDKN2A-P16 (P16INK4A) or CDKN2A-P14ARF (P14ARF) expression, important
      regulators of the RB1 and TP53 pathways, which are commonly lost or mutated in
      melanoma. These results suggest that coamplification of CDK4 and MDM2 may
      substitute for loss of P16INK4A and P14ARF function in a subset of melanomas.

PMID- 16419060
TI  - Isochromosome breakpoints on 17p in medulloblastoma are flanked by different
      classes of DNA sequence repeats.
AB  - Medulloblastoma is a highly malignant embryonal tumor of the cerebellum that
      accounts for 20%-25% of all intracranial pediatric tumors. The most frequent
      chromosomal rearrangement in medulloblastoma is isochromosome 17, or i(17q). Its
      frequency suggests that it serves an important role in tumor pathogenesis,
      possibly mediated by the disruption or permanent activation of a gene at the
      breakpoint. To address this question, we performed a detailed analysis of
      chromosome 17 DNA copy number from 18 medulloblastomas previously shown to carry
      an apparent i(17q). We identified two breakpoint regions, one well within band
      17p11.2 (n = 16) and a second within the pericentromeric region (n = 2). To map
      the breakpoints more precisely, we constructed a tiling-path matrix-CGH array
      covering chromosomal band 17p11.2 to the centromere and utilized it to delineate
      two small breakpoint intervals mapping at Mb 19.0 and 21.7 in seven of the
      medulloblastomas and in nine hematological neoplasias with i(17q). The former
      interval contains two breakpoint clusters that each colocalize with a pair of
      head-to-head inverted DNA sequence repeats, and the latter maps close to a region
      of alpha-satellite repeats. No consensus coding sequence localizes in these
      regions. Together, these data strongly suggest that the effects of i(17q) in
      medulloblastoma are mediated by gene-dosage effects of genes on 17p or 17q rather
      than by the disruption or deregulation of a "breakpoint" gene. Furthermore, we
      identified artifacts introduced in DNA copy number data by cross-hybridization of
      low-copy repeat sequences and discuss the challenge these can pose in the
      interpretation of diagnostic microarrays.

PMID- 16419061
TI  - Release of bovine serum albumin from a hydrogel-cored biodegradable polymer
      fiber.
AB  - We have developed a novel biodegradable, polymeric fiber construct that is
      coextruded using a wet-spinning process into a core-sheath format with a
      polysaccharide pre-hydrogel solution as the core fluid and poly(L-lactic acid)
      (PLLA) as the sheath. The biodegradable, biocompatible fibers were extruded from
      polymeric emulsions comprised of solutions of various molecular weights of PLLA
      dissolved in chloroform and containing dispersed, protein-free aqueous phases
      comprising up to 10% of the emulsion volume. Biologically sensitive agents can be
      loaded via a dispersed aqueous phase in the polymer, and/or directly into the
      polysaccharide. We show that this core-sheath fiber format will load a model
      protein that can be delivered for extended periods in vitro. Bovine serum albumin
      (BSA) was loaded into the fiber core as a model protein. We have shown that the
      greater the volume of the protein-free aqueous phase dispersed into the polymeric
      continuous-phase emulsion, the greater the total release of BSA encapsulated by a
      core gel comprised of 1% sodium alginate solution. We conclude this fiber format
      provides a promising vehicle for in vivo delivery of biological molecules. Its
      biocompatibility and biodegradability also allow for its use as a possible
      substrate for tissue engineering applications.

PMID- 16419063
TI  - Confounding effects of platelets on flow cytometric analysis and cell-sorting
      experiments using blood-derived cells.
AB  - BACKGROUND: Flow cytometric analysis and cell-sorting of peripheral blood
      leukocytes is commonplace; however, platelet contamination is typically ignored
      during immunophenotypic analysis and sorting of blood-derived cells. METHODS: Red
      blood cells, platelets, T & B lymphocytes, monocytes, and granulocytes were
      sorted from rat blood preparations. Presort enrichment was performed by
      differential centrifugation for all cell types. Additionally, leukocyte samples
      were prepared by ammonium chloride lysis of red blood cells. RESULTS: Unless
      proper precautions were taken, significant numbers of platelets were sorted along
      with (nonplatelet) cells of interest. The amount of platelet contamination varied
      greatly from experiment to experiment with the highest level of leukocyte
      platelet association observed in the neutrophil/granulocyte population in samples
      prepared using ammonium chloride-based red blood cell-lysing solution.
      CONCLUSIONS: Addition of an immunophenotypic marker for platelet identification
      is a simple, yet prudent, measure to help evaluate the impact of platelets on
      immunophenotypic staining when performing flow cytometric analysis or sorting of
      blood-derived cells and should become a routine practice. Platelet presence in
      postsort fractions can be due to free platelets as well as target cell-associated
      platelets and both sources of contamination must be addressed.

PMID- 16419062
TI  - Study on the redox state dependent gamma(CH) vibrational modes of the c-type
      heme.
AB  - Absorbance Fourier transform infrared (FTIR) spectra of model compounds for heme
      proteins such as protoporphyrin-IX, hemin, and hematin have been directly
      compared to the data of electrochemically induced FTIR difference spectra of
      small c-type proteins, i.e., microperoxidase-11, and cytochrome c. A band at 840
      830 cm(-1) occurring in all studied samples dominated the spectra. The position
      of this vibrational mode depends on pH and the oxidation state, and could be
      assigned to the gamma(CH) mode of the porphyrin ring. Further features, such as
      the ring vibrations sensitive for the presence of iron and its oxidation state,
      are shown in the low-frequency infrared region between 750 and 650 cm(-1).

PMID- 16419064
TI  - Static magnetic fields affect cell size, shape, orientation, and membrane surface
      of human glioblastoma cells, as demonstrated by electron, optic, and atomic force
      microscopy.
AB  - BACKGROUND: It is common knowledge that static magnetic fields (SMF) do not
      interact with living cells; thus, fewer studies of SMF compared with variable
      magnetic fields are carried out. However, evidence demonstrated that SMF affect
      cellular structures. To investigate the effect of exposure to increasing doses of
      SMF on cell morphology, human glioblastoma cells were exposed to SMF ranging
      between 80 and 3,000 G (8 and 300 mT). METHODS: Cell morphology of human
      glioblastoma cells, derived from a primary culture, was studied by electron and
      optic microscopy. FITC-phalloidin staining of actin filaments was also
      investigated. Finally, cell surface structure changes were detected by atomic
      force microscopy. RESULTS: Scanning electron microscopy demonstrated a dose
      dependent cell shape modification, progressive cell detachment, loss of the long
      villi, and appearance of membrane roughness and blebs. FITC-phalloidin staining
      confirmed the villi retention and cell dimension decrease. At 3,000 G, the
      appearance of apoptotic morphology was also observed by transmission electron
      microscopy. Cell exposed to SMF showed different orientation and alignment when
      compared with nonexposed cells. The atomic force microscopy of the exposed cells'
      membrane surfaces demonstrated the disappearance of the ordered surface ripples
      and furrows typical of the unexposed cells, and the occurrence of surface
      membrane corrugation at increasing dose exposure CONCLUSIONS: Our experimental
      procedures demonstrated that exposure to SMF affects not only cell size, shape,
      and orientation but also human glioblastoma cells' membrane surfaces.

PMID- 16419065
TI  - Ultrasonic particle-concentration for sheathless focusing of particles for
      analysis in a flow cytometer.
AB  - BACKGROUND: The development of inexpensive small flow cytometers is recognized as
      an important goal for many applications ranging from medical uses in developing
      countries for disease diagnosis to use as an analytical platform in support of
      homeland defense. Although hydrodynamic focusing is highly effective at particle
      positioning, the use of sheath fluid increases assay cost and reduces instrument
      utility for field and autonomous remote operations. METHODS: This work presents
      the creation of a novel flow cell that uses ultrasonic acoustic energy to focus
      small particles to the center of a flowing stream for analysis by flow cytometry.
      Experiments using this flow cell are described wherein its efficacy is evaluated
      under flow cytometric conditions with fluorescent microspheres. RESULTS:
      Preliminary laboratory experiments demonstrate acoustic focusing of flowing 10
      microm latex particles into a tight sample stream that is approximately 40 microm
      in diameter. Prototype flow cytometer measurements using an acoustic-focusing
      flow chamber demonstrated focusing of a microsphere sample to a central stream
      approximately 40 microm in diameter, yielding a definite fluorescence peak for
      the microspheres as compared with a broad distribution for unfocused
      microspheres. CONCLUSIONS: The flow cell developed here uses acoustic focusing,
      which inherently concentrates the sample particles to the center of the sample
      stream. This method could eliminate the need for sheath fluid, and will enable
      increased interrogation times for enhanced sensitivity, while maintaining high
      particle-analysis rates. The concentration effect will also enable the analysis
      of extremely dilute samples on the order of several particles per liter, at
      analysis rates of a few particles per second. Such features offer the possibility
      of a truly versatile low-cost portable flow cytometer for field applications.

PMID- 16419066
TI  - Single-cell analysis of siRNA-mediated gene silencing using multiparameter flow
      cytometry.
AB  - BACKGROUND: Use of synthetic short interfering RNAs (siRNAs) to study gene
      function has been limited by an inability to selectively analyze subsets of cells
      in complex populations, low and variable transfection efficiencies, and
      semiquantitative assays for measuring protein down-regulation. Intracellular flow
      cytometry can overcome these limitations by analyzing populations at the single
      cell level in a high-throughput and quantitative fashion. Individual cells
      displaying a knockdown phenotype can be selectively interrogated for functional
      responses using multiparameter analysis. METHODS: Lck-specific siRNA was
      delivered into Jurkat T cells or peripheral blood mononuclear cells (PBMCs) to
      suppress endogenous Lck expression. Transfected cells were fluorescently stained
      for intracellular Lck and analyzed using multiparameter flow cytometry. The
      Lck(lo) Jurkat subpopulation was selectively analyzed for CD69 up-regulation and
      phospho-states of signaling proteins following T-cell receptor (TCR) stimulation.
      Surface expression levels of CD4 and CD8 on transfected CD3+ gated PBMCs were
      correlated with intracellular Lck levels. RESULTS: A subpopulation of Jurkat
      cells with reduced levels of Lck was clearly resolved from cells with wildtype
      levels of Lck. Both CD69 up-regulation and ZAP70 phosphorylation were suppressed
      in Lck(lo) cells when compared with those in Lck(hi) cells upon TCR stimulation.
      Knockdown of intracellular Lck in primary T lymphocytes reduced surface
      expression of CD4 in a dose-dependent manner. CONCLUSIONS: Multiparameter flow
      cytometry is a powerful technique for the quantitative analysis of siRNA-mediated
      protein knockdown in complex hard-to-transfect cell populations.

PMID- 16419067
TI  - Crystal structure of quinolinic acid phosphoribosyltransferase from Helicobacter
      pylori.

PMID- 16419068
TI  - A population-based survey of prostate-specific antigen testing among California
      men at higher risk for prostate carcinoma.
AB  - BACKGROUND: Despite the lack of evidence demonstrating a survival benefit from
      prostate-specific antigen (PSA) screening, its use has become widespread,
      organizations have encouraged physicians to discuss early detection of prostate
      carcinoma, and two higher risk groups have been recognized. In the current study,
      the authors examined whether African-American men and men who had a family
      history of prostate carcinoma underwent PSA testing preferentially, and patterns
      of test use were examined according to age, race, and other factors. METHODS:
      Data regarding self-reported PSA test use in the past year among men age 50 years
      and older without a history of prostate carcinoma (n = 8713 men) were analyzed
      from the 2001 California Health Interview Survey. RESULTS: The overall rate of
      PSA use was 43.0%. Older age, higher socioeconomic status, having a usual source
      of healthcare, and a family history of prostate carcinoma were the strongest
      predictors of testing. Higher risk African-American men age 50 years and older
      were no more likely to be tested than white men. Men at higher risk who had a
      family history of prostate carcinoma were more likely to have been tested than
      men who had no such family history. CONCLUSIONS: Rates of PSA use among higher
      risk men who had a family history of prostate carcinoma were higher compared with
      the rates among men without such a family history. However, PSA testing rates
      among higher risk African-American men were no different than the rates among
      lower risk white men, suggesting that some risk factors for prostate carcinoma
      (but not others) are associated with preferential testing. Testing in all groups
      was associated with access to care variables, highlighting the importance of
      removing barriers to preventive healthcare services.

PMID- 16419069
TI  - Adjuvant chemotherapy in muscle-invasive bladder carcinoma: a pooled analysis
      from phase III studies.
AB  - BACKGROUND: The treatment of muscle-invasive bladder carcinoma should include
      both the eradication of local disease and the elimination of potential
      micrometastases. To date, the 'gold standard' treatment for muscle invasive
      bladder carcinoma has been recognized to be radical cystectomy. Adjuvant
      chemotherapy (AC) has the advantage of being administered to patients with known
      prognostic factors of recurrence. A pooled analysis was used to verify whether AC
      is able to increase the disease-free survival (DFS) and overall survival (OS) of
      patients with muscle-invasive bladder carcinoma who had undergone radical
      cystectomy. METHODS: All published randomized Phase III studies were considered
      eligible and a literature-based pooled analysis was accomplished. DFS and OS were
      the endpoints. Event-based relative risk ratio (RR) and 95% confidence intervals
      (95% CI) were derived. Combined effect estimation was computed with a fixed- and
      a random-effect model. A heterogeneity test was applied as well. RESULTS: Five
      trials were collected. All were evaluable for OS (350 patients) and four of these
      also were evaluable for DFS (273 patients). A significant benefit from AC was
      noted both in OS (RR, 0.74; 95% CI, 0.62-0.88 [P = 0.001]) and DFS (RR, 0.65; CI
      0.54-0.78, [P < 0.001]). No significant heterogeneity was found. CONCLUSIONS:
      Although the results of the analysis favor the use of AC, larger studies are
      needed to identify the role of AC in the treatment of muscle-invasive bladder
      carcinoma. Ongoing trials (European Organization for Research and Treatment of
      Cancer [EORTC]/Southwest Oncology Group [SWOG] and the Italian Multicentric
      Study) can help to better identify patients who can benefit from this approach.

PMID- 16419070
TI  - Prediction of buried helices in multispan alpha helical membrane proteins.
AB  - Analysis of a database of structures of membrane proteins shows that membrane
      proteins composed of 10 or more transmembrane (TM) helices often contain buried
      helices that are inaccessible to phospholipids. We introduce a method for
      identifying TM helices that are least phospholipid accessible and for prediction
      of fully buried TM helices in membrane proteins from sequence information alone.
      Our method is based on the calculation of residue lipophilicity and evolutionary
      conservation. Given that the number of buried helices in a membrane protein is
      known, our method achieves an accuracy of 78% and a Matthew's correlation
      coefficient of 0.68. A server for this tool (RANTS) is available online at
      http://gila.bioengr.uic.edu/lab/.

PMID- 16419071
TI  - Phase III study of PSC-833 (valspodar) in combination with vincristine,
      doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with
      recurring or refractory multiple myeloma (E1A95): a trial of the Eastern
      Cooperative Oncology Group.
AB  - BACKGROUND: Preliminary studies have shown valspodar (PSC-833: Novartis
      Pharmaceuticals, East Hanover, NJ) to be a potent inhibitor of multidrug
      resistance (MDR), one cause of resistance to chemotherapy. An international
      randomized control study (Phase III) evaluated the use of vincristine,
      doxorubicin, and dexamethasone (VAD) with (n = 46) and without (n = 48) valspodar
      in the treatment of patients with recurring or refractory multiple myeloma.
      METHODS: Patients with documented recurrence or refractory myeloma were
      stratified based on prior treatment exposure and creatinine and randomized.
      Because of interaction of valspodar with vincristine and doxorubicin, the doses
      of these drugs were reduced compared with the VAD-alone arm, and the doxorubicin
      was further reduced in the last 15 patients when given with valspodar based on
      pharmacokinetic and toxicity studies. RESULTS: There were no complete or near
      complete responses. There were 29% partial responses (PRs) in the VAD-alone arm
      and 44% with valspodar (P = 0.2). Median progression-free survival was 7 months
      with VAD alone and 4.9 months with valspodar (P = 0.50). Subjective response was
      19% with VAD alone and 17% with valspodar (P = 1.0). Median survival with VAD
      alone was 18.5 months and 15.3 with the addition of valspodar (P = 0.055).
      Toxicity of Grade 3 or greater was higher (P < 0.0001) in the valspodar arm (89%)
      compared with the VAD-alone arm (58%). The reduction of doxorubicin dose reduced
      toxicity but not significantly (P = 0.11). CONCLUSION: The addition of the MDR
      modulating agent valspodar to VAD did not improve treatment outcome. Toxicity was
      increased in the valspodar-treated group compared with VAD alone.

PMID- 16419072
TI  - Evaluation of complete disease remission in acute myeloid leukemia: a prospective
      study based on cytomorphology, interphase fluorescence in situ hybridization, and
      immunophenotyping during follow-up in patients with acute myeloid leukemia.
AB  - BACKGROUND: Different diagnostic methods add information to define complete
      remission (CR) in patients with acute myeloid leukemia (AML). The detection of
      minimal residual disease (MRD) for predicting prognosis and for therapeutic
      planning still are under discussion. METHODS: The authors studied 216 patients
      with AML at the time of initial diagnosis and during follow-up and correlated
      cytomorphology, interphase fluorescence in situ hybridization (FISH), and flow
      cytometry results to evaluate response status. They further tested the prognostic
      impact of those results, especially in patients who achieved a morphologic CR.
      RESULTS: Interphase FISH was found to be correlated significantly with the
      clinical course at the time of complete cytomorphologic remission and was more
      reliable than morphology for defining CR. Furthermore, interphase FISH was
      correlated with immunophenotyping results at all times during follow-up.
      CONCLUSIONS: The current results indicated that interphase FISH may be used as a
      valid MRD parameter in patients with AML. Multiparameter immunophenotyping for
      MRD also was correlated strongly with the clinical course, and the authors
      suggest integrating such immunophenotyping into the routine diagnostic panel at
      the time of diagnosis and during the clinical course in patients with AML.

PMID- 16419073
TI  - Large-amplitude fast motions in double-stranded DNA driven by solvent thermal
      fluctuations.
AB  - The nature of the internal dynamics of double-stranded DNA in aqueous environment
      remains to be established. We consider the motions to stem from thermal
      fluctuations/dissipations of the harmonic modes of beads (bases and sugars) in a
      cylindrical geometry that are tracked through the stochastic Langevin
      trajectories; these are characterized by parameters obtained from published data.
      The present approach has allowed a comparative study of the dynamics for DNA
      lengths in the range of 20-600 base pairs. For this range, we find that
      rotational motions about directions parallel to the helix axis (opening, twist)
      and perpendicular to it (propeller-twist, roll) contribute significantly to the
      dynamics. For a 20-mer at a solvent viscosity of 1 cP, the calculated
      fluorescence anisotropy profile exhibits a fast decay in the subnanosecond range
      due to large-amplitude fluctuations at the mesoscopic level. This feature
      reproduces the experimental behavior well, and suggests a possible way for the
      initiation of biological processes: they may be suddenly triggered on this scale
      through the occurrence of favorable thermal fluctuations. This analysis also
      reveals that, as is the case for a 20-mer, the dynamics of longer N-mers are
      dominated by internal motions, and are modulated by the viscosity of the solvent,
      in agreement with our previous experimental observations. Moreover, the model
      indicates that occurrence of partially concerted rotations of the bases due to
      thermal fluctuations can possibly be sustained over a DNA length of the order of
      100 A at 1 ns, suggesting a possible mechanism for action-at-a-distance in
      transcription.

PMID- 16419074
TI  - Mitoxantrone, carboplatin, cytosine arabinoside, and methylprednisolone followed
      by autologous peripheral blood stem cell transplantation: a salvage regimen for
      patients with refractory or recurrent non-Hodgkin lymphoma.
AB  - BACKGROUND: The objective of the current study was to evaluate a salvage
      chemotherapy regimen consisting of mitoxantrone, carboplatin, cytosine
      arabinoside, and methylprednisolone (MiCMA) for the treatment of patients with
      primary refractory or recurrent non-Hodgkin lymphoma (NHL). METHODS: From
      September 1991 to August 2002, 94 consecutive patients ages 16-60 years who had
      either recurrent or refractory NHL (mainly diffuse large-cell lymphomas) were
      treated on the MiCMA protocol. Patients had peripheral blood stem cells collected
      successfully for autologous stem cell transplantation after two or three cycles
      of MiCMA. RESULTS: Sixty-four of 85 evaluable patients achieved a response to the
      MiCMA regimen: 24 patients (26%) achieved a complete response and 40 patients
      (44%) achieved a partial response, for a total response rate of 70%. Sixty-two
      patients underwent autologous stem cell transplantation. After a median follow-up
      of 58 months, 47 patients (55%) remained alive; among these patients, 32 were
      free of disease (37%). No toxic deaths related to MiCMA were observed. Three
      patients died of infectious complications after transplantation. CONCLUSIONS: The
      current results suggested that MiCMA chemotherapy is an effective therapeutic
      alternative salvage regimen for patients with primary refractory or recurrent
      NHL. Response rates, overall survival, and freedom from disease progression were
      found to be associated significantly with response to MiCMA. Peripheral blood
      stem cell transplantation was feasible in virtually all patients, and its outcome
      was influenced strongly by chemosensitivity.

PMID- 16419075
TI  - Competition of cytarabine and aspirin in binding to serum albumin in multidrug
      therapy.
AB  - The aim of this study was to describe a competition between cytarabine (araC) and
      aspirin (ASA) in binding with bovine serum albumin (BSA). High-affinity binding
      sites for both drugs were determined using a spectrofluorimetric method.
      Cytarabine as well as aspirin binds in the IIA hydrophobic subdomain of the
      transporting protein. Binding constants for araC-BSA and ASA-BSA were calculated
      by the Scatchard method. Analysis of ultraviolet (UV) difference spectra showed
      that araC, which has a higher affinity to BSA in comparison to ASA [Ka(araC) >
      Ka(ASA)] displaces ASA in high-affinity binding sites. The competition between
      drugs in low-affinity binding sites was investigated using (1)H nuclear magnetic
      resonance (NMR) and 13C-NMR spectra. We concluded that in the low-affinity
      binding sites cytarabine decreases the affinity of albumin toward aspirin.
      However, the interaction between araC and BSA becomes more difficult in the
      presence of aspirin.

PMID- 16419076
TI  - From the "Modern Synthesis" to cybernetics: Ivan Ivanovich Schmalhausen (1884
      1963) and his research program for a synthesis of evolutionary and developmental
      biology.
AB  - Ivan I. Schmalhausen was one of the central figures in the Russian development of
      the "Modern Synthesis" in evolutionary biology. He is widely cited
      internationally even today. Schmalhausen developed the main principles of his
      theory facing the danger of death in the totalitarian Soviet Union. His great
      services to evolutionary and theoretical biology are indisputable. However, the
      received view of Schmalhausen's contributions to evolutionary biology makes an
      unbiased reading of his texts difficult. Here we show that taking all of his
      works into consideration (including those only available in Russian) paints a
      much more dynamic and exciting picture of what he tried to achieve. Schmalhausen
      pioneered the integration of a developmental perspective into evolutionary
      thinking. A main tool for achieving this was his approach to living objects as
      complex multi-level self-regulating systems. Schmalhausen put enormous effort
      into bringing this idea into fruition during the final stages of his career by
      combining evolutionary theory with cybernetics. His results and ideas remain
      thought-provoking, and his texts are of more than just historical interest.

PMID- 16419077
TI  - Extensive solitary fibrous tumor of the retropharyngeal space.
AB  - BACKGROUND: Solitary fibrous tumor (SFT) is a rare neoplasm whose histologic
      diagnosis poses significant problems in differential diagnosis. Although most of
      these neoplasms arise at the level of the pleura, there have also been reports of
      extrapleural origins. The most frequent localization in the head and neck region
      is in the nasal cavity. METHODS: We describe the case of an 81-year-old patient
      with an SFT that arose in the retropharyngeal space. Symptoms were solid food
      dysphagia associated with modest dyspnea. RESULTS: Physical examination revealed
      the presence on the posterior pharyngeal wall of an apparently circumscribed,
      multilobed mass, which was compact in consistency and partially obstructed the
      upper aerodigestive tract. After radiologic assessment to carefully evaluate its
      size and relationship to surrounding structures, the tumor was surgically
      removed. CONCLUSIONS: The importance of immunohistochemical findings in the
      histologic differential diagnosis are discussed. Follow-up plays a crucial role
      in evaluating the possible recurrence of such tumors, because parameters for
      determining their aggressiveness are still controversial.

PMID- 16419078
TI  - Expression of Cux-1 and Cux-2 in the developing somatosensory cortex of normal
      and barrel-defective mice.
AB  - Recently, two orthologues of the Drosophila homeobox Cut gene, Cux-1 and Cux-2,
      have been identified as restricted molecular markers of upper layer (II-IV)
      neurons in the murine cerebral cortex. We show that during early postnatal life,
      from P0 to P10, Cux-1 and Cux-2 mRNA are coexpressed in all primary sensory
      cortices. Antisera to Cux-1 and Cux-2 immunoreactivities preferentially label
      neurons in the barrel walls of the primary somatosensory cortex (S1).
      Subsequently, Cux-1 remains enriched in sensory cortices, whereas Cux-2
      expression enlarges to comprise the frontal and insular areas. The laminar
      distribution of Cux-1 and Cux-2 differs: Cux-1 follows a layer IV to layer II
      decreasing gradient of expression, whereas Cux-2 expression is homogeneous across
      layers IV-II. No colocalization was found with GABA and birth dating experiments
      showed that Cux-1-positive neurons in layer IV are born during a restricted
      period, E13.5-E14.5, suggesting that Cux-1 is a useful molecular marker of the
      glutamatergic neurons of layer IV. We examined Cux-1 and Cux-2 in barrel
      defective mouse strains, the VMAT2 KO, the MAOA KO, and the Adcyl 1(brl) strain.
      A normal expression level of Cux-1 and Cux-2 was found in layer IV, despite the
      lack of segregation of the neurons as barrels. Conversely, in Reeler mice, Cux-1
      and Cux-2 had a distinct laminar distribution: the Cux-1-positive neurons had an
      inverted deep localization, whereas the Cux-2-positive neurons were distributed
      throughout the cortical thickness, suggesting that Cux-2 expression is more
      widely expressed in the inverted cortex of reeler mutants. Our results indicate
      that Cux-1 is a useful marker of the layer IV neurons in S1, and that Cux-1 and
      Cux-2 are differently regulated in the upper layers of the cerebral cortex.

PMID- 16419079
TI  - Adult extracardiac rhabdomyoma: light and immunohistochemical studies of two
      cases in the parapharyngeal space.
AB  - BACKGROUND: We present two cases of adult rhabdomyoma in the parapharyngeal
      space. They are rare benign tumors with a characteristic histologic appearance.
      METHODS: The tumors were studied by light and immunohistochemical analysis using
      stains characteristic of striated muscle fibers. RESULTS: Cross-striation was
      demonstrated by phosphotungstic acid hematoxylin (PTAH), muscle specific actin,
      desmin, and myoglobin while dystrophin was expressed in the cell membranes.
      Clonal origin was confirmed by expression of myosin heavy chain-fast only.
      Expression of myosin-neonatal and myogenin proved slight proliferation with
      incipient differentiation in an otherwise mature tumor. CONCLUSION: The head and
      neck area harbors 90% of adult rhabdomyomas and should be considered in a
      differential diagnosis in this region. Immunohistochemistry confirms that the
      tumors are almost totally mature neoplasms of clonal origin.

PMID- 16419080
TI  - Efficacy of routine bilateral neck dissection in the management of the N0 neck in
      T1-T2 unilateral supraglottic cancer.
AB  - BACKGROUND: The treatment of the clinically negative (N0) neck in supraglottic
      laryngeal cancer continues to be an area of controversy. The aim of this study
      was to analyze the long-term efficacy of routine bilateral neck dissection
      compared with ipsilateral neck dissection in T1-T2 N0 lateral supraglottic
      carcinomas. METHODS: A retrospective review of 108 patients who underwent surgery
      for T1-T2 supraglottic squamous cell carcinoma was performed. Forty-eight had
      undergone ipsilateral functional neck dissection, and 60 had undergone bilateral
      functional neck dissections. None of these patients received adjuvant
      radiotherapy. RESULTS: No significant differences (p = .78) in regional
      recurrence were observed between the patients treated with bilateral neck
      dissection (13%) and those treated with ipsilateral neck dissection (17%). The 5
      year survival rates were 73% and 80% for the patients who received a bilateral
      and ipsilateral neck dissection, respectively (p = .51). CONCLUSIONS: This study
      suggests that routine bilateral neck dissection may not be necessary in the
      surgical treatment of all supraglottic cancers.

PMID- 16419081
TI  - A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer
      risk in BRCA2 mutation carriers.
AB  - Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of
      developing breast and other cancers; however, remarkable differences exist
      regarding disease manifestation in mutation carriers. It has been suggested that
      other genetic and/or environmental factors modify not only the appearance but
      also the age of onset and type of tumor in BRCA1/2-associated cases. The aim of
      the present study was to investigate the role of two p53 polymorphisms (c.97
      147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we
      investigated the possible association between the two polymorphisms and disease
      status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or
      ovarian cancer families. Genotype and haplotype analyses revealed that the
      presence of a specific haplotype carrying the allele without the 16-bp insertion
      and the variant allele for the Arg72Pro (No Ins-72Pro haplotype) was associated
      with an earlier age of onset in BRCA2 mutation carriers. We found an increased
      risk of developing a first primary tumor (breast or ovarian) before 35 years of
      age for individuals who carried at least one No Ins-72Pro haplotype (OR: 2.69;
      95% CI: 1.15-6.29; P=0.022). We confirmed these data by a functional study in
      which we compared different p53 genotypes in relation to their apoptotic response
      after cell treatment with a cytotoxic drug (AraC). Our results revealed a
      decrease in p53 apoptotic rate associated with the No Ins-72Pro haplotype.

PMID- 16419082
TI  - 2005 Human Genome Variation Society Scientific Meeting.
AB  - The Annual Scientific Meeting of the Human Genome Variation Society (HGVS) was
      held on 25 October 2005 in Salt Lake City, Utah. There were four sessions
      covering topics of interest to members of the HGVS, including mutations and
      phenotypes, gene variation and disease, methodological approaches, and mutation
      databases. At this year's annual meeting there was an emphasis on the inclusion
      of phenotypic information into genomic variation databases. The addition of this
      information will require the coordinated effort of many individuals from a
      variety of organizations to ensure that databases will be searchable and
      meaningful in this effort to combine genomic information, functional data
      associated with variation, epidemiological data (including environmental
      exposure), and phenotypic information (especially phenotypes associated with
      disease). The human genome era is moving into a new phase, and these talks are
      representative of the new directions in which the study of human DNA variation is
      going in this exciting area of research.

PMID- 16419083
TI  - RNAi-based suppression and replacement of rds-peripherin in retinal organotypic
      culture.
AB  - Extensive mutational heterogeneity presents a significant barrier to the
      development of therapeutics for RDS-peripherin-linked autosomal-dominant
      retinitis pigmentosa (RP), for which more than 50 disease-related mutations have
      been identified to date. Mutation-independent suppression, using RNA interference
      (RNAi), together with simultaneous expression of a replacement rds gene (r-rds,
      which has been altered to escape suppression but nevertheless encodes wild-type
      protein) has been explored in COS-7 cells and mouse retinal explants. The
      efficacy of small interfering and short hairpin RNAs (si/shRNAs) silencing mouse
      rds, and the function of r-rds (containing degenerate substitutions in the RNAi
      target sequence) were analyzed at transcript (RT-PCR) and protein (ELISA) levels
      in COS-7 cells. "Dual-" and "triple-expression" constructs carrying the shRNA
      suppressor and the marker EGFP with or without the r-rds cassette were
      electroporated in vitro into retinal explants from 1-day-old pups. The retinae
      were dissociated at day 14, and transduced cells were FACS-sorted using the
      coexpressed EGFP marker and analyzed by RT-PCR. si/shRNAs decreased rds mRNA and
      protein expression by up to 82%, while r-rds was protected from suppression in
      COS-7 cells. Similarly, efficient RNAi-mediated suppression of endogenous rds was
      detected in retinal explants, while concomitant rescue of r-rds was also
      achieved. These data validate the concept of RNAi-based suppression coupled with
      replacement technology for the development of therapies targeting RDS-linked
      autosomal-dominant RP, and suggest that such approaches could potentially be used
      for other autosomal-dominant diseases with similarly extensive intragenic
      heterogeneity.

PMID- 16419084
TI  - Photoprotein aequorin as a novel reporter for SNP genotyping by primer extension
      application to the variants of mannose-binding lectin gene.
AB  - Mannose-binding lectin (MBL) is a key component of the innate immune system, and
      its deficiency is associated with increased susceptibility to various infections
      and autoimmune disorders. Since several nucleotide variations in the mannose
      binding lectin 2 gene (MBL2) have been associated with the functional deficiency
      of MBL, there is a growing need to screen its allelic variants and develop
      genotyping methods for MBL2. In this context we propose a rapid, robust, cost
      efficient, and automatable method for detecting all known allelic variants of
      MBL2. This report introduces for the first time the photoprotein aequorin as a
      reporter in genotyping by primer extension (PEXT) reactions. The method involves
      a single PCR amplification of a genomic region that spans all six variant
      nucleotide sites, i.e., three structural mutations in exon 1 (c.154C>T,
      pArg52Cys; c.161A>G, p.Gly54Asp; and c.170A>G, p.Gly57Glu), two single nucleotide
      polymorphisms (SNPs) at positions c.-619G>C and c.-290G>C (promoter region), and
      one SNP at position c.-66C>T of the 5' untranslated region. PCR is followed by
      PEXT reactions for each site. Biotin-dUTP is incorporated in the extended primer.
      The genotyping primers contain a poly(dA) segment at their 5' end. The products
      are captured by hybridization on the surface of microtiter wells that are coated
      with a poly(dT)-albumin. The extended primers only are detected by reaction with
      a streptavidin-aequorin conjugate. The bound photoprotein aequorin is measured
      within 3 sec by simply adding Ca2+. We carried out extensive optimization studies
      of the PEXT reaction and genotyped the six nucleotide variant sites using blood
      specimens from 27 normal DNA samples. The results of the proposed method agreed
      entirely with the sequencing data.

PMID- 16419085
TI  - PTCH mutations: distribution and analyses.
AB  - Mutations in the PTCH (PTCH1) gene are the underlying cause of nevoid basal cell
      carcinoma syndrome (NBCCS), and are also found in many different sporadic tumors
      in which PTCH is thought to act as a tumor suppressor gene. To investigate the
      distribution pattern of these mutations in tumors and NBCCS, we analyzed 284
      mutations and 48 SNPs located in the PTCH gene that were compiled from our PTCH
      mutation database. We found that the PTCH mutations were mainly clustered into
      the predicted two large extracellular loops and the large intracellular loop. The
      SNPs appeared to be clustered around the sterol sensing domain and the second
      half of the protein. The NBCCS cases and each class of tumor analyzed revealed a
      different distribution of the mutations in the various PTCH domains. Moreover,
      the types of mutations were also unique for the different groups. Finally, the
      PTCH gene harbors mutational hot spot residues and regions, including a slippage
      sensitive sequence in the N-terminus.

PMID- 16419086
TI  - Central visual system of the naked mole-rat (Heterocephalus glaber).
AB  - Naked mole-rats are fossorial rodents native to eastern Africa that spend their
      lives in extensive subterranean burrows where visual cues are poor. Not
      surprisingly, they have a degenerated eye and optic nerve, suggesting they have
      poor visual abilities. However, little is known about their central visual
      system. To investigate the organization of their central visual system, we
      injected a neuronal tracer into the eyes of naked mole-rats and mice to compare
      the neural structures mediating vision. We found that the superior colliculus and
      lateral geniculate nucleus were severely atrophied in the naked mole-rat. The
      olivary pretectal nucleus was reduced but still retained its characteristic
      morphology, possibly indicating a role in light detection. In addition, the
      suprachiasmatic nucleus is well innervated and resembles the same structure in
      other rodents. The naked mole-rat appears to have selectively lost structures
      that mediate form vision while retaining structures needed for minimal
      entrainment of circadian rhythms. Similar results have been reported for other
      mole-rat species. Taken together, these data suggest that light detection may
      still play an important role in the lives of these "blind" animals: most likely
      for circadian entrainment or setting seasonal rhythms.

PMID- 16419087
TI  - Proteomic analysis of microglial contribution to mouse strain-dependent
      dopaminergic neurotoxicity.
AB  - Although the pathogenesis of Parkinson's disease (PD) remains unknown, it appears
      that microglial activation is associated with enhanced neurodegeneration in
      animal models of PD as well as in PD patients. Experimentally, C57BL/6 and SWR/J
      mice demonstrate striking differences in the extent of dopaminergic (DAergic)
      neurodegeneration induced by a parkinsonian toxicant 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). The purpose of this study was to determine whether
      differences in microglial activation between these two strains of mice could
      provide insight into the variability seen in toxicant induced neuronal death, and
      subsequently to use a high-throughput proteomic method, combining stable isotope
      labeling with amino acids in cell culture (SILAC) with liquid chromatography and
      tandem mass spectrometry, to compare the microglial proteomes of C57BL/6 and
      SWR/J mice after stimulation with a classical microglial activator,
      lipopolysaccharide (LPS). We found that DAergic neurotoxicity induced by LPS in a
      primary neuron-microglia coculture was twofold greater with microglia isolated
      from the brains of C57BL/6 mice compared with that of SWR/J mice. Upon proteomic
      analysis we found that, out of over 1,000 proteins identified and quantified, 400
      displayed a significant difference in their relative abundance between these two
      murine strains. Several proteins, which had relatively higher levels in C57BL/6
      mice, have previously been implicated in LPS-mediated microglial activation,
      including those involved in the COX-2 pathway and in prostaglandin E-2 (PGE(2))
      production. To validate our proteomic results we confirmed the increased
      expression level of iNOS in C57BL/6 vs. SWR/J microglia with semiquantitative
      Western blot. Further analysis of our proteomic discovery data will likely reveal
      numerous novel proteins involved in inflammation-mediated neurotoxicity in PD.

PMID- 16419088
TI  - Alpha-tocopherol (vitamin E) induces rapid, nonsustained proliferation in
      cultured rat microglia.
AB  - Microglial cells undergo cell division in vitro, as well as in vivo after brain
      injury. Mitotic activity of microglia suggests that they have limited life spans
      and rely on self-renewal to replace senescent cells. In the current study we
      examined long-term effects of antioxidants vitamin E and alpha-lipoic acid on
      cultured rat microglia with respect to proliferative ability, telomere length,
      telomerase activity, and interleukin-1beta (IL-1beta) production. We report that
      vitamin E induces dramatic microglial proliferation, as measured by MTT assay and
      BrdU incorporation, surpassing that of the well-known microglial mitogen
      granulocyte macrophage-colony stimulating factor, and therefore establishing
      vitamin E as the most potent, known mitogen for microglia in vitro. The high rate
      of microglial proliferation resulted in a concomitant decrease in telomere length
      and telomerase activity. Production of IL-1beta was significantly decreased in
      vitamin E-treated microglia in vitro. Our findings provide an impetus to
      investigate potential benefits of vitamin E supplementation on microglial renewal
      capacity in vivo during aging or after brain injury.

PMID- 16419089
TI  - Murine glia express the immunosuppressive cytokine, interleukin-10, following
      exposure to Borrelia burgdorferi or Neisseria meningitidis.
AB  - There is growing appreciation that resident glial cells can initiate and/or
      regulate inflammation following trauma or infection in the central nervous system
      (CNS). We have previously demonstrated the ability of microglia and astrocytes,
      resident glial cells of the CNS, to respond to bacterial pathogens by rapid
      production of inflammatory mediators. However, inflammation within the brain
      parenchyma is notably absent during some chronic bacterial infections in humans
      and nonhuman primates. In the present study, we demonstrate the ability of the
      immunosuppressive cytokine, interleukin-10 (IL-10), to inhibit inflammatory
      immune responses of primary microglia and astrocytes to B. burgdorferi and N.
      meningitidis, two disparate gram negative bacterial species that can cross the
      blood-brain barrier in humans. Importantly, we demonstrate that these organisms
      induce the delayed production of significant quantities of IL-10 by both
      microglia and astrocytes. Furthermore, we demonstrate that such production occurs
      independent of the actions of bacterial lipopolysaccharide and is secondary to
      the autocrine or paracrine actions of other glia-derived soluble mediators. The
      late onset of IL-10 production by resident glia following activation, the
      previously documented expression of specific receptors for this cytokine on
      microglia and astrocytes, and the ability of IL-10 to inhibit bacterially induced
      immune responses by these cells, suggest a mechanism by which resident glial
      cells can limit potentially damaging inflammation within the CNS in response to
      invading pathogens, and could explain the suppression of inflammation seen within
      the brain parenchyma during chronic bacterial infections.

PMID- 16419090
TI  - Optimized beta-galactosidase staining method for simultaneous detection of
      endogenous gene expression in early mouse embryos.
AB  - beta-Galactosidase (beta-gal) is one of the popular reporters for detecting the
      expression of endogenous or exogenous genes. Here we report 6-chloro-3-indoxyl
      beta-D-galactopyranoside (S-gal) is more sensitive for beta-gal activity than 5
      bromo-4-chloro-3-indolyl-beta-D-galactoside (X-gal), particularly during the
      early developmental stages of mouse embryos. Further, we successfully combined
      beta-gal staining with S-gal and in situ hybridization using DIG-labeled probes
      in both whole and sections of early stage embryos due to the sensitivity and
      color compatibility of S-gal.

PMID- 16419091
TI  - Plasma-lead concentration: investigations into its usefulness for biological
      monitoring of occupational lead exposure.
AB  - BACKGROUND: The lead concentration in plasma is correlated to that in whole blood
      with a two to fourfold variation. It has never been investigated if this
      variation is inter-individual. METHODS: Lead and hemoglobin were determined in
      blood and plasma from 13 lead workers with a history of relatively high blood
      lead concentrations, sampled three times during 1 day. The variation in the
      distribution of lead between cells and plasma was studied, but not the variation
      in the lead concentrations as such. RESULTS: Blood hemoglobin decreased with
      rising plasma lead (0.9-3.0 microg/L). Regarding the distribution of lead, no
      effect of current exposure during the day or of recent meals appeared. As much as
      84% of the overall variance of the distribution of lead between cells and plasma
      could be attributed to individual factors. After adjustment for erythrocyte
      volume fraction this decreased to 67%. Plasma samples with elevated hemoglobin
      concentrations (due to in vitro hemolysis) had somewhat elevated lead
      concentrations. CONCLUSIONS: Plasma lead is not significantly altered by
      variation in a single day's exposure and, therefore, the choice of time of the
      day is not critical for sampling. However, plasma lead is negatively correlated
      to blood hemoglobin and mild hemolysis (not visible by the eye) in a sample may
      increase plasma lead with up to 30%. Finally, plasma provides lead exposure
      information that differs from whole blood, but it is not clear which one of these
      is the biomarker with the closest relation to exposure and/or effects.

PMID- 16419094
TI  - Etiologic yield of autistic spectrum disorders: a prospective study.
AB  - Studies addressing etiologic yield in childhood developmental disabilities have
      mainly looked at individuals with developmental delay/mental retardation. The few
      studies addressing the question of etiologic yield in patients with pervasive
      developmental disorders (PDDs) had a major drawback, in that the enrolled
      subjects were diagnosed as having the autistic spectrum disorders based only on
      history and clinical examination, and/or on unspecified instruments. In addition,
      only some of these patients underwent a complete laboratory evaluation. To
      investigate the etiologic yield of PDDs, we undertook a large prospective study
      on subjects selected according to very strict criteria and diagnosed as having
      PDD based on the present "gold standard" (ADI-R and ADOS-G), and a clinical
      diagnosis made by a child psychiatrist. Eighty-five (85) patients with PDD and
      their first degree relatives participated in this study. These patients were
      selected from a sample of 236 subjects who had received a clinical diagnosis of
      PDD at the Stella Maris Institute between March 2002 and 2005. Selection criteria
      for entering the study were: (1) a diagnosis of PDD (with exclusion of the Rett
      syndrome) confirmed after the administration of the ADI-R (autism diagnostic
      interview-revised) and the ADOS-G (autism diagnostic observation schedule
      generic). In addition, a clinical diagnosis was made by the child psychiatrist,
      on the basis of presence or absence of DSM-IV symptoms of autism; (2)
      chronological age between 4 and 18 years; (3) IQ>30; (4) availability of both
      biologic parents. Patients, 65/85 (76.5%), had autism, 18/85 (21.2%) had PDD-NOS,
      and the remaining 2/85 (2.3%) had Asperger syndrome. Ages varied between 4 years
      2 months and 12 years 5 months (mean 7.6 years), and there was a marked male
      preponderance (68/85). All subjects underwent various laboratory studies and
      neuroimaging. With respect to possible etiologic determination, a detailed
      history and physical examination in this group of patients with PDD was
      informative in 10.5% (9/85). HRB karyotype was diagnostic in one, and molecular
      fragile X studies in one child. Brain MRI was informative in two children (2.3%)
      with relative macrocrania but no neurological features; and EEG was helpful in
      one child, identifying a Landau-Kleffner disorder. Audiometry and brainstem
      auditory evoked potentials (BAEPs) showed a bilateral sensorineural loss in
      another child. Metabolic evaluation gave normal results in all subjects. The
      results suggest an evaluation paradigm with reference to etiologic determination
      for individuals with PDDs that does not presently justify metabolic or
      neuroimaging on a screening basis. Recurrence risk, treatment implications, and
      significant and long-lasting emotional relief for the parents suggest that
      serious consideration be given to clinical genetic examination, genetic testing,
      EEG study (during wakefulness and sleep), and audiometry, despite a relatively
      low yield.

PMID- 16419092
TI  - Eye and respiratory symptoms in poultry processing workers exposed to chlorine by
      products.
AB  - BACKGROUND: CDC/NIOSH responded to a request to investigate complaints of eye and
      respiratory irritation among workers in a poultry processing facility's
      evisceration department. METHODS: Investigators administered symptom
      questionnaires and sampled for chlorine and chloramines. Spirometry was performed
      on workers before and after their work shift. RESULTS: Symptoms were
      significantly more prevalent in evisceration workers than in dark meat workers (a
      control group). Air concentrations of chloramine compounds (i.e., trichloramine
      and 'soluble chlorine') were significantly higher in the evisceration area than
      the dark meat area. Exposure levels were significantly higher for employees
      reporting various symptoms compared to employees not reporting those symptoms.
      Mean trichloramine exposure concentrations were significantly higher in workers
      with significant cross-shift declines in lung function; air concentrations of
      'soluble chlorine' were higher as well, however, not significantly so.
      CONCLUSIONS: Results of this evaluation suggest a health hazard may exist from
      exposure to chloramines.

PMID- 16419095
TI  - The yield of subtelomeric FISH analysis in the evaluation of autistic spectrum
      disorders.
AB  - To assess the frequency of cryptic subtelomeric rearrangements in children and
      adolescents with autism spectrum disorders, blood samples were studied using a
      complete set of subtelomeric FISH probes in 72 children with autism spectrum
      disorders. All children had normal high resolution karyotype, DNA fra-X analysis,
      brain MRI, metabolic work-up, and physical/neurological examination. Subtelomeric
      analysis did not detect abnormalities in any of the subjects, suggesting the
      uselessness of such investigations in individuals with primary autism spectrum
      disorders.

PMID- 16419096
TI  - Autism spectrum disorders: molecular genetic advances.
AB  - Despite the strong genetic basis of autism spectrum disorders (ASD), research
      efforts in the last decade have not been successful in the identification of
      confirmed susceptibility genes. We review the present status of genetic linkage,
      candidate gene, and association studies, pointing out the limitations of these
      approaches and the challenge of dealing with the clinical and genetic complexity
      of autism. Finally, we outline how recent technological and bioinformatic
      advances, together with an increasing understanding of the structure of the human
      genome, have set the stage to perform more comprehensive and well powered
      studies, possibly leading to a turning point in the understanding of the genetic
      basis of this devastating disorder.

PMID- 16419097
TI  - Current perspectives on the genetic analysis of autism.
AB  - Although no definitive genetic mutations leading to autism susceptibility have
      been established, the field has many new resources to tackle this difficult
      problem. Numbers of families at many research sites are now large, and new
      collaborations among these groups will allow for collections of subjects with
      enough statistical power to detect relatively small gene effects. New
      technological advances in genotyping will allow for more fine-grained genetic
      analysis, and more sophisticated techniques have been developed to address the
      vast amounts of data acquired. Researchers have also begun to focus on
      intermediate phenotypes associated with autism, such as elevated serotonin,
      increased head circumference, social difficulties, or language impairment or
      delay. These phenotypes may help to stratify affected cases into more genetically
      homogeneous subgroups, and may also occur in their clinically unaffected
      relatives. The study of intermediate phenotypes may allow investigators to find
      common gene variants that lead to autism susceptibility. Here we discuss the
      major intermediate phenotypes, and give an overview of current genetic analysis
      techniques.

PMID- 16419098
TI  - Advances in autism neuroimaging research for the clinician and geneticist.
AB  - This review focuses on recent advances in the in vivo study of the whole brain in
      idiopathic autism. The brain is abnormally large in some but not all children
      with autism during post-natal development. Age-related changes in brain volume in
      autism are complex and appear to be abnormal from infancy into adulthood. Diffuse
      differences in total and regional gray and white matter volumes are found. The
      volumetric abnormalities appear to follow anomalous, complex, and non-uniform
      developmental curves. Diffuse abnormalities of brain chemical concentrations,
      neural network anatomy, brain lateralization, intra- and inter-hemispheric
      morphologic and functional connectivity, and serotonin synthesis capacity are
      also found. Abnormalities of head growth are first apparent during infancy.
      Abnormalities of total brain volume, gray and white matter volumes, brain
      chemistry, serotonin synthesis, and brain electrophysiology are evident by early
      childhood. Currently, no method of brain imaging helps with diagnosis or
      treatment of idiopathic autism, but ongoing research aims to unravel the
      heterogeneity of autism and may provide future diagnostic tools that inform
      treatment.

PMID- 16419099
TI  - Mouse models of autism spectrum disorders: the challenge for behavioral genetics.
AB  - Autism is a severe neurodevelopmental disorder, which typically emerges early in
      childhood. The core symptoms of autism include deficits in social interaction,
      impaired communication, and aberrant repetitive behavior, including self-injury.
      Despite the strong genetic component for the disease, most cases of autism have
      not been linked to mutations in a specific gene, and the etiology of the disorder
      has yet to be established. At the present time, there is no generally accepted
      therapeutic strategy to treat the core symptoms of autism, and there remains a
      critical need for appropriate animal models and relevant behavioral assays to
      promote the understanding and treatment of the clinical syndrome. Challenges for
      the development of valid mouse models include complex genetic interactions
      underlying the high heritability of the disease in humans, diagnosis based on
      deficits in social interaction and communication, and the lack of confirmatory
      neuropathological markers to provide validation for genetic models of the
      disorder. Research focusing on genes that mediate social behavior in mice may
      help identify neural circuitry essential for normal social interaction, and lead
      to novel genetic animal models of the autism behavioral phenotype.

PMID- 16419100
TI  - Genetic counseling and ethical issues for autism.
AB  - Exciting progress is being made in the journey toward discovery of genes
      conferring risk for autism and autism spectrum disorders. Currently, genetic
      counseling for idiopathic autism rests on clinical diagnosis and empiric risk
      estimates. While no genetic test for risk of autism currently exists, it is
      possible that such a test may emerge in the near future, and that commercial
      availability may precede adequate understanding of test characteristics. The
      complexity of multifactorial conditions like autism raises a host of ethical and
      counseling challenges. For families to benefit from new genetic knowledge about
      autism, it will be important for their practitioners to be knowledgeable about
      the issues, utilize appropriate educational interventions and emerging management
      options, and help families across the cultural spectrum cope with these
      challenges.

PMID- 16419101
TI  - BAC array CGH reveals genomic aberrations in idiopathic mental retardation.
AB  - Array using 2,173 BAC clones covering the whole human genome has been
      constructed. All clones spotted were confirmed to show a unique signal at the
      predicted chromosomal location by FISH analysis in our laboratory. A total of 30
      individuals with idiopathic mental retardation (MR) were analyzed by comparative
      genomic hybridization using this array. Three deletions, one duplication, and one
      unbalanced translocation could be detected in five patients, which are likely to
      contribute to MR. The constructed array was shown to be an efficient tool for the
      detection of pathogenic genomic rearrangements in MR patients as well as copy
      number polymorphisms (CPNs).

PMID- 16419102
TI  - Obstructive sleep apnea in Costello syndrome.
AB  - Costello syndrome (CS) was initially described by Costello in 1971; it is caused
      by a germline mutation in HRAS proto-oncogene. The aim of the present study was
      to evaluate the respiratory activity during sleep in a group of subjects with CS.
      We studied 10 consecutive patients, 4 males and 6 females, aged 3-29 years,
      affected by CS. All patients underwent clinical, neurological, otholaryngologic
      and radiologic evaluation, and a full-night polysomnography in the sleep
      laboratory. Polysomnography showed that seven patients presented a relevant
      number of respiratory events of obstructive type during sleep. The apnea-hypopnea
      index (AHI) ranged from 0 to 19.2 events per hour (mean index = 7.5 +/- 6.9
      events/hr). In one patient AHI was not evaluable because of tracheostomy. Apnea
      induced mild or moderate hemoglobin desaturations (mean of lowest SpO2 values =
      85.4 +/- 5.5%). Only sporadic respiratory pauses of central type were observed
      (mean number of central apnea per study: 7.2 +/- 6.8 events/hr). Sleep structure
      was fragmented, with a high number of awakenings (mean number of awakenings was
      13.2 +/- 8.1; of these, 4.8 +/- 2.5 lasted longer than 2 min). In all patients,
      otolaryngologic and radiologic observations revealed one or more sites of
      narrowing in the upper airways. Our results suggest that Costello patients have a
      high prevalence of obstructive sleep-related respiratory disorders, which need to
      be assessed by means of polysomnography.

PMID- 16419104
TI  - Effect of sugar type on the survival of frozen-thawed rhesus monkey (Macaca
      mulatta) sperm.
AB  - Sperm-freezing extenders supplemented with sugar or a combination of different
      sugars are widely used for the cryopreservation of nonhuman primate spermatozoa.
      Understanding which sugar or combination of sugars offers the highest level of
      cryoprotection would be beneficial for the development of sperm-freezing
      extenders. In the present study we aimed to investigate the effect of glucose,
      lactose, and raffinose separately or in combination on the cryosurvival of rhesus
      monkey spermatozoa. Toward that end, we prepared eight extenders by adding
      various types of sugars to a basic medium (BM): G-BM (0.3 M glucose), L-BM (0.3 M
      lactose), R-BM (0.3 M raffinose), LG-BM (0.15 M lactose+0.15 M glucose), RG-BM
      (0.15 M raffinose+0.15 M glucose), LR-BM (0.15 M lactose+0.15 M raffinose), and
      LRG-BM (0.1 M lactose+0.1 M raffinsoe+0.1 M glucose). A saline control (0.157 M
      sodium chloride) was also used. The results showed no significant difference in
      post-thaw motility when spermatozoa were frozen with G-BM, L-BM, LG-BM, RG-BM,
      and LRG-BM, but the post-thaw motility was significantly lower when it was frozen
      with R-BM, LR-BM, and the saline control. The highest plasma membrane integrity
      was achieved when spermatozoa were frozen with G-BM, L-BM, LG-BM, RG-BM, and LRG
      BM, and the highest acrosome integrity was achieved with G-BM, L-BM, LG-BM, RG
      BM, LRG-BM, and the saline control. The results indicate that the various sugars
      offered different protective effects. For the cryopreservation of rhesus monkey
      spermatozoa, glucose (monosaccharide) and lactose (disaccharide) were shown to be
      more suitable than raffinose (trisaccharide) for preserving spermatozoal
      motility, plasma membrane, and acrosome. Specifically, raffinose was detrimental
      to sperm acrosome integrity.

PMID- 16419105
TI  - One-male units and clans in a colony of hamadryas baboons (Papio hamadryas
      hamadryas): effect of male number and clan cohesion on feeding success.
AB  - In the multilevel societies of hamadryas baboons, adult males can be attached to
      single one-male units (OMUs) or to clans containing several such OMUs. This paper
      examines the effect of male number and rivalry between males within a clan on
      their ability to compete for access to a clumped food resource. The data come
      from a study of a multilevel colony of hamadryas baboons (Papio hamadryas
      hamadryas) housed at the Madrid Zoo. The colony consisted of 12 harem-holding
      males and 40 sexually mature females, and was organized into five single OMUs and
      two clans (containing three and four OMUs, respectively). The top-ranking male of
      one of the clans was removed and later reintroduced, so the study involved an
      analysis of the composition of clans and OMUs and of the males' use of the
      feeding area across three study periods: preseparation, separation, and
      reintroduction. The findings reported indicate that both males and females
      derived clear advantages in the context of contest competition for access to
      clumped food if they were members of clans, because the males and females from
      large clans had a feeding advantage over those from smaller clans and single
      OMUs. Furthermore, rivalry among males within the clan reduced their ability to
      compete for food against males outside their clan. This paper provides empirical
      evidence for one of the potential advantages that hamadryas males may enjoy if
      they are attached to clans, and also provides empirical support for the general
      hypothesis that a large number of males in a group may provide fitness-related
      benefits to the group members, provided they are able to cooperate with each
      other.

PMID- 16419103
TI  - Characterization of neurochemically specific projections from the locus coeruleus
      with respect to somatosensory-related barrels.
AB  - Tactile information from the rodent mystacial vibrissae is relayed through the
      ascending trigeminal somatosensory system. At each level of this pathway, the
      whiskers are represented by a unique pattern of dense cell aggregates, which in
      layer IV of cortex are known as "barrels." Afferent inputs from the dorsal
      thalamus have been demonstrated repeatedly to correspond rather precisely with
      this modular organization. However, axonal innervation patterns from other brain
      regions such as the noradrenergic locus coeruleus are less clear. A previous
      report has suggested that norepinephrine-containing fibers are concentrated in
      the center/hollow of the barrel, while other studies have emphasized a more
      random distribution of monoaminergic projections. To address this issue more
      directly, individual tissue sections were histochemically processed for
      cytochrome oxidase in combination with dopamine-beta-hydroxylase, the
      synthesizing enzyme for norepinephrine, or the neuropeptide galanin. These two
      neuroactive agents were of particular interest because they colocalize in a
      majority of locus coeruleus neurons and terminals. Our data indicate that
      discrete concentrations or local arrays of dopamine-beta-hydroxylase- or galanin
      immunoreactive fibers are not apparent within the cores of individual barrels. As
      such, the data suggest that cortical inputs from the locus coeruleus are not
      patterned according to cytoarchitectural landmarks or the neurochemical identity
      of coeruleocortical efferents. While transmitter-specific actions of
      norepinephrine and/or galanin may not be derived from the laminar/spatial
      connections of locus coeruleus axons, the possibility remains that the release of
      these substances may mediate distinctive events through the localization of
      different receptor subclasses, or the contact of their terminals onto cells with
      certain morphological characteristics or ultrastructural components.

PMID- 16419106
TI  - Molecular epidemiology of hepatitis B virus in Dakar, Senegal.
AB  - Using DNA chip technology and real-time quantitative PCR, molecular profile of
      HBV strains infecting blood donors and patients in Dakar, Senegal was studied.
      All HBsAg-positive blood donors (n = 175) and all patients who presented with
      chronic hepatitis B (n = 29) between 1st June 2003 and 31st July 2003 were
      studied. One patient, a blood donor, was coinfected by HCV, and nine patients had
      anti-HDV antibodies. Few persons in either group were HBeAg-positive. Viral load
      values were relatively low but correlated with biochemical abnormalities.
      Patients were infected mainly by genotype E (72%). Patients infected by genotype
      A (28%) tended to be younger than other patients. There was no significant
      difference between the blood donors and the patients with hepatitis B as regards
      virological markers, including viral load, when the HBV genotype was taken into
      account. The BCP A1762T and G1764A mutations were found in four patients and one
      patient, respectively; the two mutations were never found in the same patient.
      The W28* mutation at position 1896 of the core was detected in 19 of the 32
      genotyped patients, 18 (83%) of whom had genotype E infection. ALT levels were
      not influenced by HBV mutations. This study shows a low frequency of clinical
      signs in HBsAg-positive blood donors, a relatively low level of viral
      replication, and a high frequency of pre-core mutants in this West African
      population. These results underline the importance of molecular characterization
      of HBV infection as specific treatments become available in this region.

PMID- 16419108
TI  - Genetic variability in BK Virus regulatory regions in urine and kidney biopsies
      from renal-transplant patients.
AB  - The human Polyomavirus BK (BKV) contains a hypervariable non-coding control
      region (NCCR), which regulates DNA replication and RNA transcription. The aim of
      this study was to characterize BKV NCCR-variants in kidney biopsies and urine
      samples from renal-transplant patients and to see whether there is any
      association between NCCR variability and BKV-nephropathy. Kidney biopsies and
      urine samples were examined from 11 patients with elevated serum creatinine and
      >5,000 genomic BKV copies per ml of urine. BKV-nephropathy was diagnosed in seven
      patients. Using PCR, BKV NCCR was amplified from urine from all BKV-nephropathy
      patients. The dominant NCCR corresponded to the archetype (WWT). In addition, a
      total of 14 non-archetype NCCR-variants were detected. Thirteen of these NCCR
      variants were found in urine from one single BKV-nephropathy patient also
      suffering from hepatitis C. The NCCR of BKV was amplified from kidney biopsies of
      six BKV-nephropathy patients. Three patients demonstrated WWT NCCR, while three
      other patients harbored rearranged NCCR variants. The WWT NCCR was also detected
      in urine from control patients, except for one patient who harbored two non
      archetypal NCCR variants. However, these variants were not resulting from complex
      rearrangements but instead had a linear NCCR anatomy with deletion(s) in the P
      block. No BKV DNA was detected in biopsies from control patients. The results
      indicate that rearranged BKV NCCR is associated with BKV-nephropathy.

PMID- 16419107
TI  - Twenty-four hour kinetics of hepatitis C virus and antiviral effect of alpha
      interferon.
AB  - Numerous studies reported that patients infected by the genotype 1 of hepatitis C
      virus (HCV) and/or with a high baseline viral load responded poorly to antiviral
      therapy. Study of viral kinetics has provided clues to the understanding of non
      response to alpha-interferon (IFN-alpha)-based therapy. The objective of this
      study was to clarify the influence of viral factors such as the genotype and
      baseline viral load on HCV resistance to treatment through the study of their
      impact on the first phase of viral decline. HCV RNA levels were determined
      frequently following the administration of 3 million units of IFN-alpha in 22
      chronic HCV carriers. The evolution of HCV RNA level over 24 hr was different in
      genotype 1-infected patients, compared to that in patients infected by other
      genotypes. The viral load decline at 24 hr was lower in patients with genotype 1.
      Patients with a high baseline viral load exhibited a viral dynamics different
      from patients with a lower level of viremia; the extent of the first phase was
      also lower in these patients. Non-responder patients had a slower viral decay on
      day 1 of therapy than patients who cleared the virus under treatment. In
      conclusion, 24 hr HCV dynamics is regulated by genotype and baseline viral load.
      Genotype 1 strains and those that produce high viral loads are the most resistant
      to the antiviral action of IFN-alpha. Resistant HCV strains could be
      distinguished from sensitive viruses as early as a few hours after the beginning
      of the treatment.

PMID- 16419109
TI  - Evaluation of apoptosis in Epstein-Barr virus-associated hemophagocytic
      lymphohistiocytosis.
AB  - Epstein-Barr virus (EBV) is known to be a causative agent of hemophagocytic
      lymphohistiocytosis (HLH). To investigate association of apoptosis in the
      pathogenesis of EBV-associated HLH, the serum EBV loads, and serum concentrations
      of soluble tumor necrosis factor receptor 1 (sTNF-R1), soluble Fas ligand, and
      cytochrome c were examined in 15 patients with EBV-associated HLH and 24 patients
      with infectious mononucleosis (IM). Levels of sTNF-R1 are known to reflect the
      biological activity of TNF-alpha and cytochrome c is a specific marker of
      apoptosis. EBV loads, and concentrations of sTNF-R1 and cytochrome c were
      significantly higher in patients with EBV-associated HLH than in patients with
      IM. On the other hand, there were no statistically significant differences in the
      concentrations of soluble Fas ligand. In patients with EBV-associated HLH, EBV
      loads, concentrations of sTNF-R1, and cytochrome c were correlated with each
      other. These results suggest that apoptosis, which is dependent on the EBV load
      and could be mediated by TNF-alpha, plays a major role in the pathophysiology of
      EBV-associated HLH.

PMID- 16419110
TI  - Impact of human metapneumovirus and human cytomegalovirus versus other
      respiratory viruses on the lower respiratory tract infections of lung transplant
      recipients.
AB  - Viral respiratory tract infections in lung transplant recipients may be severe.
      During three consecutive winter-spring seasons, 49 symptomatic lung transplant
      recipients with suspected respiratory viral infection, and 26 asymptomatic
      patients were investigated for presence of respiratory viruses either in 56
      nasopharyngeal aspirate or 72 bronchoalveolar lavage samples taken at different
      times after transplantation. On the whole, 1 asymptomatic (3.4%) and 28
      symptomatic (57.1%) patients were positive for human metapneumovirus (hMPV, 4
      patients), influenza virus A (3 patients), and B (2 patients), respiratory
      syncytial virus (2 patients), human coronavirus (2 patients), human parainfluenza
      virus (2 patients), rhinovirus (5 patients), while 4 patients were coinfected by
      2 respiratory viruses, and 5 were infected sequentially by 2 or more respiratory
      viruses. In bronchoalveolar lavage samples, hMPV predominated by far over the
      other viruses, being responsible for 60% of positive specimens, whereas other
      viruses were present in nasopharyngeal aspirates at a comparable rate. RT-PCR
      (detecting 43 positive samples/128 examined) was largely superior to monoclonal
      antibodies (detecting 17 positive samples only). In addition, HCMV was detected
      in association with a respiratory virus in 4/18 HCMV-positive patients, and was
      found at a high concentration (>10(5) DNA copies/ml) in 3/16 (18.7%) patients
      with HCMV-positive bronchoalveolar lavage samples and pneumonia. Coinfections and
      sequential infections by HCMV and respiratory viruses were significantly more
      frequent in patients with acute rejection and steroid treatment. IN CONCLUSION:
      (i) about 50% of respiratory tract infections of lung transplant recipients were
      associated with one or more respiratory viruses; (ii) hMPV largely predominates
      in bronchoalveolar lavage of symptomatic lung transplant recipients, thus
      suggesting a causative role in lower respiratory tract infections; (iii) RT-PCR
      appears to be the method of choice for detection of respiratory viruses in lung
      transplant recipients, (iv) a high HCMV load in bronchoalveolar lavage is a risk
      factor for viral pneumonia, suggesting some measure of intervention for the
      control of viral infection.

PMID- 16419111
TI  - The first B/G intersubtype recombinant form of human immunodeficiency virus type
      1 (HIV-1) identified in Germany was undetected or underquantitated by some
      commercial viral load assays.
AB  - The high level of genetic diversity of human immunodeficiency virus type 1 (HIV
      1) and the continual emergence of recombinant forms have important implications
      not only for the global evolution of HIV but also for diagnosis, monitoring, and
      treatment strategies. The present study reports the first intersubtype B/G
      recombinant strain of HIV-1 in Germany. This strain is notable from a clinical
      perspective, since it was undetectable in the NucliSens HIV-1 QT assay (Organon
      Tecknika/bioMerieux) and was significantly underquantitated in the Monitor v1.5
      test (Roche Molecular Systems) relative to the LCx HIV RNA Quantitative assay
      (Abbott Laboratories). Gag-encoded p24 (gag p24), pol-encoded integrase (pol IN),
      and env-encoded gp41 (env gp41) immunodominant region (IDR) sequences were
      characterized to establish group and subtype designation and to evaluate the
      degree of genetic diversity at primer and probe binding sites of the viral load
      assays. Phylogenetic analysis revealed that this virus is an intersubtype B/G
      recombinant strain. The gag p24 region is subtype G, env gp41 IDR is subtype B,
      and pol IN is a B/G chimera. Nucleotide mismatches within primer and probe
      binding sites provided the molecular basis for differences in quantitation
      observed between viral load assays. Genetic diversity of HIV-1 continues to
      challenge the reliability of detection and quantitation by viral load assays.

PMID- 16419112
TI  - Fatal liver failure with the emergence of hepatitis B surface antigen variants
      with multiple stop mutations after discontinuation of lamivudine therapy.
AB  - Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is
      effective and well-tolerated. However, discontinuation of the treatment is
      associated frequently with acute exacerbation of liver diseases. A patient
      suffering from acute liver failure after discontinuation of lamivudine treatment
      is described. The patient was treated with lamivudine for 4 months and ceased the
      treatment without consulting. After receiving lamivudine, the patient developed
      anti-HBs and became negative for hepatitis B surface antigens (HBsAg). However,
      HBV DNA reappeared to a level of 6.47 x 10(5) copies/ml. The patient died due to
      acute liver failure. Sequencing of HBV isolates revealed that mutations including
      G145R and stop codons occurred within the HBsAg coding region. In conclusion, HBV
      replication resumed after the uncontrolled cessation of lamivudine treatment in
      this patient and may have triggered the process leading to liver failure. Anti
      HBs antibody appeared and may be the selective force for the emergence of HBV
      mutants.

PMID- 16419113
TI  - Significance of hepatitis B virus genotypes A to E in a cohort of patients with
      chronic hepatitis B in the Seine Saint Denis District of Paris (France).
AB  - The aim of this study was to examine the genetic variability of the hepatitis B
      virus (HBV) and its significance. HBV genotypes, core promoter and precore
      mutants were characterized in 109 consecutive patients with biopsy-proven HBV
      chronic hepatitis. Genotypes A (26.6%), B (12.8%), C (18.3%), D (18.3%), and E
      (14.7%) indicate a wide genotypic distribution. Patients were from Asia (30.3%),
      Europe (28.4%), Sub Saharan Africa (23.9%), the Caribbean (10.1%), North Africa
      (5.5%), and Madagascar (1.8%). HBV genotypes A and D (HBV/A and /D) infected all
      subgroups except Asian patients. HBV/B or /C were found in 97% of Asian patients,
      whereas HBV/E only infected sub-Saharan African and Caribbean patients.
      Differences according to genotypes were: an increased prevalence of anti-HBe
      antibodies in patients infected with HBV/D (P = 0.003), higher serum
      transaminases in patients infected with HBV/A and/D (P = 0.043), more severe
      liver fibrosis in patients infected with HBV/A, /C and/D (P = 0.02). Precore and
      core promoter mutants were found in 87% of anti-HBe positive patients, and were
      associated with HBV/D (P = 0.04) and severe liver fibrosis (P = 0.002). It is
      concluded that HBV genotypes A, B, C, D, and E circulate in the Seine Saint Denis
      District, reflecting the geographical origin of patients. HBV/A, /C and/D seem to
      be associated with more severe hepatic disease.

PMID- 16419114
TI  - Hepatitis B virus genotyping, core promoter, and precore/core mutations among
      Afghan patients infected with hepatitis B: a preliminary report.
AB  - In spite of hepatitis B virus (HBV) vaccination, HBV infection remains an
      important public health problem worldwide. Although the HBV genotype distribution
      has been determined in some parts of South Central Asia, no survey has been
      conducted to determine the HBV genotype in Afghanistan. Twelve Afghan patients
      infected with HBV living in Afghanistan were enrolled in this study. Partial
      HBsAg and basic core promoter, precore, and core (BCP/preC/C) regions were
      amplified and subjected for direct sequencing. In parallel, precore G1896A
      mutation was also determined by an amplification-created restriction site method.
      Results revealed HBV genotype D (95% bootstrap value), sub-genotype D1 (98%
      bootstrap value), and subtype ayw2 in all Afghan isolates. Afghan isolates
      clustered in a separate branch in the D1 sub-genotype called D1', while supported
      by 82% bootstrap value. The percentage of intra-genotypic distance among Afghan
      isolates was 1.05% and inter-genotypic distance with the other genotype D was
      2.87% and with other genotypes was 7.50%-11.1%. The wild-type, mixed infection,
      and precore mutant were found in six, two, and four HBV isolates, respectively.
      The A1762T/G1764A BCP dual mutation was found in one isolate. Three isolates
      presented single mutation in the BCP dual mutation region, whereas two showed a
      novel G1764T mutation. In conclusion, this preliminary study revealed HBV
      genotype D, sub-genotype D1, and subtype ayw2 of HBV among hepatitis B infected
      patients from Afghanistan. Further investigation should be carried out.

PMID- 16419115
TI  - Epidemiology of Kaposi's Sarcoma herpesvirus (HHV8) in Vasterbotten County,
      Sweden.
AB  - A population-based serosurvey of Human Herpesvirus type 8 (HHV8) in Vasterbotten
      County, an area of Northern Sweden with high incidence of Kaposi's Sarcoma, was
      conducted. Serum samples from an age- and sex-stratified random sample of 520
      subjects (260 men and 260 women) participating in a population-based biobanking
      project were tested for antibodies against HHV8, using a sensitive indirect
      immunofluorescence assay to latent and lytic HHV8 antigens. Buffy coat DNA was
      also analyzed for viral DNA using real time PCR assay. HHV8 DNA was not
      detectable in any one of the buffy coat samples. Eighty-four subjects (16.2%)
      were HHV8 seropositive, 14.4% for the lytic HHV8 antigen, and 1.7% for the latent
      HHV8 antigen. HHV8 seroprevalences were not associated significantly with sex or
      age. HHV8 seropositivity was more common among smokers (OR: 1.95, 95% CI: 1.02
      3.75), but was less common among consumers of wine and spirits (OR: 0.44, 95% CI:
      0.25-0.77 and OR: 0.50, 95% CI: 0.26-0.95, respectively). In summary, HHV8 has an
      intermediate high and stable seroprevalence rate in Northern Sweden, but
      environmental determinants that can explain the viral distribution were not
      found.

PMID- 16419116
TI  - Clinical and virological features of non-breakthrough and severe exacerbation due
      to lamivudine-resistant hepatitis B virus mutants.
AB  - Patients who develop YMDD mutant during lamivudine therapy for hepatitis B virus
      (HBV) infection exhibit various clinical courses. Some patients show normal ALT
      levels, whereas others develop severe hepatitis exacerbations (SHEs) due to YMDD
      mutants. We studied 136 patients with YMDD mutant among 362 Japanese adult
      patients on lamivudine therapy. Clinical and virological features of patients
      without elevated HBV DNA after emergence of YMDD mutant (non-elevated group) were
      investigated. Moreover, virological analysis was also performed in patients with
      SHE due to YMDD mutants. Patients in the non-elevated group were characterized by
      HBeAg-negative pretreatment, HBeAg loss during therapy, a longer duration from
      commencement of therapy until emergence of YMDD mutant, and no mixed-type YMDD
      mutants. Patients with SHE had more substitutions in the reverse transcriptase
      (rt) region within the polymerase gene at the time of exacerbation than those
      without SHE, although no specific substitutions were noted. Sequence analysis of
      full-length HBV genome showed more substitutions in X, rt, and surface proteins
      in patients with SHE than in those without elevated HBV DNA level. In conclusion,
      negativity for HBeAg at commencement of therapy or before emergence of YMDD
      mutant was an important factor among non-elevated group. More substitutions in
      the rt region and the other proteins may be related to the emergence of severe
      hepatitis caused by lamivudine-resistant virus.

PMID- 16419117
TI  - Genetic heterogeneity of the hexon gene of adenovirus type 3 over a 9-year period
      in Korea.
AB  - Hexon sequences were analyzed in 29 epidemiologically unrelated adenovirus type 3
      (Ad3) isolates from the 7 genome types to understand the molecular basis of the
      genome-type diversity of Ad3 associated with childhood pneumonia in Korea during
      the period 1991-1999. Nine nucleotide substitutions were observed among the 29
      Ad3 strains. Five of the 9 involved amino acid changes in loops 1 (Gly to Val at
      codon 205 and Thr to Ile at 211) and loop 2 (His to Asn at 417, Thr to Ala at
      429, and Ala to Asp at 439). The predicted hydropathic characteristics of this
      region have been affected by these amino acid changes. The region surrounding
      codons from 417 to 439 of Ad3a16 and Ad3a18 manifested greater hydrophobicity
      than the region of other genome types (Ad3a, Ad3a13, Ad3a14, Ad3a15, and Ad3a17).
      In particular, three amino acid changes in loop 2 were associated with two new
      genome types, namely, Ad3a16 and Ad3a18, which were recognized during later
      epidemics in 1998-1999. Phylogenetic relatedness revealed that these two genome
      types clustered into distinct lineages in the phylogenetic tree. This result
      suggests that the genetic heterogeneity of Ad3 hexon could play a potential role
      in the appearance of new genome types and that it could affect the antigenic
      characteristics of Ad3.

PMID- 16419118
TI  - Severe graft rejection, increased immunosuppression, and active CMV infection in
      renal transplantation.
AB  - Associations between active cytomegalovirus (CMV) infection, graft rejection,
      rejection therapy, and clinical signs and symptoms have been shown repeatedly.
      However, the causes and the sequence of events remain an area of debate. Two
      hundred twenty five patients with cadaveric renal transplant were included in the
      present study. Clinical signs and symptoms, and the development of active CMV
      infections were recorded during the first 3 months after renal transplantation.
      CMV monitoring by pp65-antigenemia was performed followed by preemptive antiviral
      therapy. Delayed graft function and severe graft rejection followed by anti T
      cell antibody therapy was associated with the development of active CMV
      infection. In contrast, the induction therapy with anti-T-cell antibodies was not
      associated with more active CMV infections. Post-transplant morbidity determined
      by fever, pneumonia, and duration of hospital stay was increased significantly in
      patients with active CMV infection. However, in times of preemptive antiviral
      therapy an increased morbidity occurred in association with severe graft
      rejection and not with active CMV infection alone. In patients with renal
      transplantation and preemptive antiviral therapy, the morbidity was no more
      influenced by the CMV serostatus although the prevalence of active CMV infection
      was obviously different between CMV exposed (D+/R+,D+/R-, D-/R+) and unexposed (D
      /R-) patients. Severe graft rejection and increased immunosuppression could
      stimulate cooperatively active CMV infections whereas immunosuppression alone may
      not be as effective. Prevention of severe graft rejection may be important to
      decrease early post-transplant morbidity and also the development of active CMV
      infections after renal transplantation.

PMID- 16419119
TI  - Calling in wild silvery gibbons (Hylobates moloch) in Java (Indonesia): behavior,
      phylogeny, and conservation.
AB  - Hardly any behavioral data are available for the silvery gibbon (Hylobates
      moloch), an endangered primate that is endemic to the island of Java, Indonesia.
      We studied the singing behavior of the easternmost population of this species in
      the Dieng mountains, central Java, in 1998-1999. We aimed to document the timing
      of singing, quantify the amount of singing by the respective sexes, and explore
      the role of bioacoustics in density estimation. A total of 122 song bouts in at
      least 12 groups were monitored. No duet songs were heard. Most of the song bouts
      (91.5%) were female solo song bouts or female scream bouts. In contrast to an
      earlier study on the westernmost population of silvery gibbons, during which few
      if any male songs were heard, at least 8.5% of the song bouts in our study were
      male solo song bouts. They were significantly longer in duration than the female
      songs. All male song bouts uttered before dawn (0520 hr) were produced in a
      chorus fashion, with at least three individuals participating. Choruses occurred
      about once every 8.5 days, and lasted longer and occurred earlier than female
      solo song bouts. Most male songs (60%) started between 0355-0440 hr, when it was
      still dark. All female songs, in contrast, started after 0500 hr, and female
      singing activity peaked around 0600. Regular male singing, male chorusing, and
      regular predawn singing have not previously been reported for silvery gibbons.
      Similarly separated periods of male and female solo songs and the absence of
      duetting have been observed in Kloss's gibbons (H. klossii) on the Mentawai
      Islands, and may represent synapomorphies shared by both species. The pronounced
      individual-specific song characteristics of silvery gibbons allow accurate
      mapping of groups. The density of gibbons at our study site was established to be
      1.9-3.7 groups/km2, corresponding to 6.7-13.1 individuals/km2. We reassess the
      suitability of gibbon songs as a means of estimating the density and size of
      gibbon populations, and discuss the proximate causes for the absence of duetting
      in silvery gibbons.

PMID- 16419120
TI  - Comparative studies with six extenders for sperm cryopreservation in the
      cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta).
AB  - Ejaculated spermatozoa from cynomolgus monkeys and rhesus monkeys were frozen in
      straws with six different extenders (TTE, DM, mDM, LG-DM, G-DM, and TCG)
      containing glycerol. Sperm motility and head membrane and acrosomal integrity
      were evaluated after freezing and thawing, and the cryoprotective effects were
      compared among the extenders and the two species studied. The results showed that
      sperm motility and motility recovery with the six extenders were comparable for
      the cynomolgus and rhesus monkeys. There was no significant difference in sperm
      motility and head membrane integrity among the six extenders in either the
      cynomolgus or rhesus monkeys (P>0.05). However, a slightly but statistically
      lower percentage of acrosomal integrity was found with TCG in both species
      compared to the other extenders (P<0.05). These findings demonstrate that TTE,
      DM, mDM, LG-DM, G-DM, and TCG are equally suitable extenders for the
      cryopreservation of spermatozoa from cynomolgus and rhesus monkeys.

PMID- 16419121
TI  - Microsatellite markers for standardized genetic management of captive colonies of
      rhesus macaques (Macaca mulatta).
AB  - To preserve genetic variability and minimize genetic subdivision among captive
      Macaca mulatta at each of the U.S. National Institutes of Health (NIH)-sponsored
      regional research colonies, the genetic structure of each colony must be
      characterized. To compare population genetic and demographic parameters across
      colonies and generations, one standard panel of highly informative genetic
      markers is required. We assembled a core marker set of four multiplex polymerase
      chain reaction (PCR) panels comprising 15 autosomal short tandem repeat (STR)
      loci with high information content selected from existing panels of well
      characterized markers that are currently used for parentage assessment and
      genetic management of rhesus macaques. We then assessed the effectiveness of
      these loci for providing high probabilities of individual identification and
      parentage resolution, and for estimating population genetic parameters that are
      useful for genetic management.

PMID- 16419122
TI  - Bioactive properties of plant species ingested by chimpanzees (Pan troglodytes
      schweinfurthii) in the Kibale National Park, Uganda.
AB  - We measured the biological activities of a selected sample (84 crude extracts) of
      24 species eaten by wild chimpanzees (Pan troglodytes schweinfurthii) in the
      Kibale National Park, western Uganda, to assess their potential chemotherapeutic
      values. Antibacterial, antimalarial, and/or antileishmania activities were
      observed in some crude extracts, and five of these extracts showed a significant
      cytotoxicity against human tumor cells. Active compounds isolated from three
      plant parts occasionally ingested by chimpanzees (Diospyros abyssinica
      (Ebenaceae) bark, Uvariopsis congensis (Annonaceae) leaves, and Trichilia
      rubescens (Meliaceae) leaves) showed highly significant medicinal properties. Two
      novel antiparasitic limonoids were isolated from Trichilia rubescens and their
      molecular structures were determined. In addition to elucidating the natural
      equilibrium maintained between hosts and pathogens, our investigation of the diet
      of wild chimpanzees may serve as a guideline to discovering plants with bioactive
      properties that should be preserved from destruction because of their health
      maintenance value for great ape populations.

PMID- 16419123
TI  - Troop fission in wild ring-tailed lemurs (Lemur catta) at Berenty, Madagascar.
AB  - A detailed fission process in a wild ring-tailed lemur (Lemur catta) troop was
      observed at Berenty Reserve, Madagascar. The troop fission occurred as follows:
      1) During the birth season in 2000, two adult females (mother and daughter) were
      evicted as a result of "targeted aggression" (i.e., intense and persistent
      aggressive behavior toward particular individuals). 2) Two adult and three
      immature females in the same kin group as the evicted females spontaneously
      immigrated into the new group. 3) A male immigrated into the new group 1.5 months
      later. 4) The new troop successfully established its own home range. This report
      exemplifies three characteristics of troop fission in ring-tailed lemurs. First,
      targeted aggression initiated the fission process. Second, the troop females
      divided along matrilineal lines. Finally, no male played a specific role in the
      fission process.

PMID- 16419124
TI  - Levels of HSP70 in HIV(+) patients in different viroimmunological states.
AB  - The aim of the study was to establish an association between the
      viroimmunological status of HIV positive patients and their levels of the 70-kD
      heat shock protein (Hsp70). The longitudinal retrospective case study involved 61
      patients at the University Hospital in Granada (Spain) from 1999 to 2002. Twenty
      five patients were viroimmunologically stable, while the other 36 patients had
      suffered virological failure. A minimum of three blood samples were taken at
      intervals of at least 3 months for the patients who were stable virologically and
      immunologically, whereas four samples were taken for the virological failure
      group: two previous to the onset of virological failure, a third corresponding to
      the time of virological failure, and a fourth at least 3 months after remission
      of virological failure. Blood samples were also obtained from 20 healthy control
      subjects; Hsp70 levels in all were determined by enzyme immunoassay. The mean
      concentration of Hsp70 was 145.4 ng/ml in the HIV-infected patients as opposed to
      72.1 ng/ml in the controls. While the viroimmunologically stable group showed
      levels similar to those of the controls (66.5 ng/ml), the mean value of Hsp70 in
      the virological failure group was nearly four times as high (249.1 ng/ml), yet
      this difference was not statistically significant. The patients treated with
      reverse transcriptase inhibitors were found to have significantly higher levels
      of Hsp70 than the other subjects. The transformed variable Hsp70/CD4(+) presents
      less variability than the Hsp70 value itself, giving a higher degree of
      statistical significance, and may be considered a useful parameter for
      diagnostic, prognostic, and therapeutic management of HIV positive patients.

PMID- 16419125
TI  - Hepatitis B genotypes, precore and core promoter mutants circulating in Tunisia.
AB  - Hepatitis B virus (HBV) is characterized by genetic heterogeneity, including
      genotypes and mutations. Eight genotypes (A-H) have been identified throughout
      the world with a characteristic geographical distribution. Previous studies also
      suggest that the viral genotypes may correlate with differences in clinical
      features of the infection. Two types of mutations were particularly described,
      precore and basal promoter mutations; they may play an important role in the
      clinical outcome of HBV infection. The aim of this study was to investigate the
      prevalence of HBV genotypes and HBV variants in Tunisia, and their eventual
      association with severity of liver disease. Using a molecular method, HBV
      genotypes, precore and basal core promoter mutations were determined in 56
      asymptomatic carriers and in 82 patients with histologically verified chronic
      liver disease and hepatocellular carcinoma (HCC). Three genotypes (D, A, and E)
      were detected; the prevalence was 80%, 8%, and 9%, respectively. No significant
      difference was observed for genotype D with clinical status. HBV mutants were
      detected in 93% of cases, precore mutants were the most prevalent. Basal core
      promoter mutants were observed in 61% of cases, they were frequently
      characterized by a double mutation in 1762 and 1764. Co-infection by these two
      types of mutants was detected in 50% of cases. Genotype D was the most prevalent
      HBV genotype in Tunisia. High circulation of precore and basal core promoter
      mutants are common in chronic hepatitis B infection in Tunisia.

PMID- 16419126
TI  - 18q deletions: clinical, molecular, and brain MRI findings of 14 individuals.
AB  - We studied 14 individuals with partial deletions of the long arm of chromosome
      18, including terminal and interstitial de novo and inherited deletions. Study
      participants were examined clinically and by brain MRI. The size of the deletion
      was determined by segregation analysis using microsatellite markers. We observed
      that the phenotype was highly variable, even in two families with three 1st
      degree relatives. Among the 14 individuals, general intelligence varied from
      normal to severe mental retardation. The more common features of 18q-deletions
      (e.g., foot deformities, aural atresia, palatal abnormalities, dysmyelination,
      and nystagmus) were present in individuals lacking only the distal portion
      18q22.3-qtel. Interstitial deletions exerted very heterogeneous effects on
      phenotype. In individuals with distal 18q22.3-q23 deletions, brain MRI was very
      distinctive with poor differentiation of gray and white matter on T2-weighted
      images.

PMID- 16419127
TI  - Schimke immuno-osseous dysplasia: a cell autonomous disorder?
AB  - SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of
      chromatin, subfamily a-like protein 1) encodes a SWI/SNF ATP-dependent chromatin
      remodeling protein. Mutations in SMARCAL1 cause the autosomal-recessive
      multisystem disorder Schimke immuno-osseous dysplasia (SIOD); this suggests that
      the SMARCAL1 protein is involved in the development or maintenance of multiple
      organs. Disease within these many tissues could arise by a cell autonomous or a
      cell non-autonomous mechanism. Consistent with a cell autonomous mechanism, we
      did not find any disease recurrence in transplanted organs or protection of other
      tissues by the organ grafts. In order to better understand the role of SMARCAL1
      during normal development and in the pathogenesis of SIOD, we characterized the
      spatial and temporal expression of the murine homolog (Smarcal1). The Smarcal1
      mRNA and protein were expressed throughout development and in all tissues
      affected in patients with SIOD including the bone, kidney, thymus, thyroid,
      tooth, bone marrow, hair, eye, and blood vessels. Significantly, the expression
      profile of Smarcal1 in the mouse has led us to reexamine and identify novel
      pathology in our patient population resulting in changes in the clinical
      management of SIOD. The expression of Smarcal1 in affected tissues and the non
      recurrence of disease in grafted organs lead us to hypothesize a cell autonomous
      function for SMARCAL1 and to propose tissue-specific mechanisms for the
      pathophysiology of SIOD.

PMID- 16419128
TI  - Andersen-Tawil syndrome: prospective cohort analysis and expansion of the
      phenotype.
AB  - Andersen-Tawil syndrome (ATS) is an autosomal dominant multisystem disorder
      characterized by developmental, cardiac, and neuromuscular abnormalities.
      Approximately 70% of patients have mutations in KCNJ2, resulting in dysfunction
      of the inward-rectifying potassium channel Kir2.1. Variable expression
      complicates the diagnosis of ATS, which in many cases, is not made until years
      after the first recognized symptom. To better define the distinctive clinical
      features of ATS and facilitate earlier diagnosis, we conducted a prospective,
      standardized evaluation of 10 subjects with confirmed KCNJ2 mutations. Detailed
      anthropometric, neurological, and cardiac evaluations were performed. Using this
      approach, we identified novel skeletal and dental findings and proposed
      additional diagnostic criteria for ATS dysmorphology.

PMID- 16419129
TI  - Familial congenital non-immune hydrops, chylothorax, and pulmonary
      lymphangiectasia.
AB  - Pulmonary lymphangiectasia is an uncommon congenital anomaly, and familial
      occurrence has rarely been reported. We report on two sibs with bilateral pleural
      effusion/chylothorax and hydrops who died neonatally. One sib required prenatal
      intrauterine hemithoracic drainage. Autopsy confirmed congenital pulmonary
      lymphangiectasia (CPL) histologically in the first case. Hydrops, characterized
      as subcutaneous edema and effusions in two or more body cavities, may be due to a
      variety of factors, but the co-occurrence of CPL in one of these sibs, although
      rare, supports the notion that chylothorax and hydrops may be caused by
      structural lesions of lymph channels. Although most cases of CPL are sporadic,
      the reported sibs support autosomal recessive inheritance, with intrafamilial
      variability of a lymphatic disorder on a genetic basis. Mutations in vascular
      endothelial growth factor receptor-3 (VEGFR3) in families with Milroy disease,
      mutations of FOXC2 in the lymphedema-distichiasis syndrome, and fatal chylothorax
      in alpha9-deficient mice are potential candidate genes.

PMID- 16419130
TI  - Narrowing candidate region for monosomy 9p syndrome to a 4.7-Mb segment at 9p22.2
      p23.
AB  - A 2-year-old boy with clinical manifestations of monosomy 9p syndrome and brown
      hair is described. G-banding and chromosome FISH studies demonstrated complex
      rearrangements involving seven breakpoints in chromosomes 2 and 9, which included
      a 6.6-Mb deletion at 9p22.2-p23. This, together with previous studies in the
      literature, narrowed the shortest region of overlap (SRO) for the syndrome to a
      4.7-Mb interval. Candidate genes for trigonocephaly, mental retardation, and
      brown hair are discussed.

PMID- 16419131
TI  - The use of inappropriate, demeaning, and pejorative terminology to describe
      syndromes.

PMID- 16419133
TI  - A subterminal deletion of the long arm of chromosome 10: a clinical report and
      review.
AB  - We report on a girl with mental retardation, dysmorphic features, and behavioral
      problems. A small terminal deletion of the long arm of chromosome 10 was detected
      by subtelomeric fluorescence in situ hybridization (FISH) studies in all analyzed
      metaphases. The deletion was shown to be a de novo terminal deletion of
      approximately 6.1 Mb, with the deletion breakpoint localized at band 10q26.2,
      between BAC probes RP11-498K22 and RP11-42K2. A subterminal 10q deletion as found
      in the present patient has, to our knowledge, only been reported in 15 patients
      (including 8 familial cases). We review the clinical and behavioral phenotype of
      these patients with "pure" subterminal 10q deletion.

PMID- 16419134
TI  - Cleidocranial dysplasia plus vascular anomalies with 6p21.2 microdeletion
      spanning RUNX2 and VEGF.

PMID- 16419136
TI  - Association of Jacobsen syndrome and bipolar affective disorder in a patient with
      a de novo 11q terminal deletion.
AB  - We report on a young woman with Jacobsen syndrome (JBS) who was admitted to our
      psychiatric department because of a bipolar affective disorder (BPAD). Chromosome
      analysis was performed due to the fact that she had mental retardation, short
      stature, and subtle facial anomalies. A deletion of the distal long arm of
      chromosome 11 was found. A detailed mapping of the deletion breakpoint by
      quantitative real time PCR revealed a true terminal 11q deletion of approximately
      8 Mb corresponding to the karyotype 46,XX,del(11)(q24.2). Polymorphic DNA marker
      analysis showed that the deletion is located on the paternal chromosome.
      Additionally, laboratory investigations revealed a low platelet count and
      magnetic resonance imaging of the brain showed white matter T2 hyperintensities
      in frontotemporal regions, which are unlikely to result from a demyelinating
      process as indicated by localized proton magnetic resonance spectroscopy. To our
      knowledge, this is the first report describing a BPAD in a case with JBS.

PMID- 16419135
TI  - A microdeletion in Xp11.3 accounts for co-segregation of retinitis pigmentosa and
      mental retardation in a large kindred.
AB  - In a previous report, Aldred et al. [1994] described a 5-generation family in
      which severe retinitis pigmentosa (RP) co-segregates with mild-moderate mental
      retardation as an X-linked recessive phenotype mapping to the broad interval
      between Xp21-q21. We re-examined this family, initially analyzing RP2, a gene in
      the disease interval that was identified as a cause of RP after the initial
      report of this family. We found that the male propositus lacked the 5' three
      exons of RP2 and that RP2 marks the centromeric boundary of a 1.27 Mb deletion
      that includes two other annotated genes (SLC9A7, CHST7), one predicted transcript
      encoding a zinc finger protein (FLJ20344) and two highly conserved miRNAs
      (mir221, mir222). We conclude that this family is segregating a contiguous gene
      deletion and that the absence of a functional RP2 accounts, at least in part, for
      the retinal degeneration while deletion of one or more of the other genes is
      likely responsible for the mental retardation phenotype.

PMID- 16419137
TI  - Manifestations in a family with autosomal dominant bone fragility and limb-girdle
      myopathy.
AB  - We report on an unusual family with an autosomal dominant limb-girdle type of
      myopathy and bone fragility. This family was previously reported by Henry et al.
      [1958] as autosomal dominant progressive limb girdle "muscular dystrophy" with
      propensity to fractures and defective healing of long bones. Clinical,
      biochemical, and radiological aspects were evaluated in eight living relatives in
      this family (three males and five females) and in eight deceased individuals. The
      average age-of-onset of the limb-girdle myopathy was 31 years occurring in 87% of
      affected individuals. The average age of onset of fractures was 24 years
      occurring in 88% of affected individuals. Biochemical analysis showed a mean
      alkaline phosphatase (ALP) of 64 U/L (normal 30-120) and borderline high creatine
      kinase (CK) of 213 U/L (normal 4-220). Radiographs revealed coarse trabeculation,
      patchy sclerosis, cortical thickening, and narrowing of the medullary cavity with
      an appearance not considered typical of Paget disease of bone (PDB) or of fibrous
      dysplasia. Results of nerve conduction studies were normal, and electromyograms
      and muscle biopsies documented non-specific myopathic changes. There is premature
      graying with thin hair, thin skin, hernias and the affected individuals appear
      older than their chronological age, and three members had a clotting disorder.
      Linkage analysis for markers for the chromosome 9p22.3-q12 locus indicated that
      the disorder in this family does not segregate with markers in the critical
      region of limb-girdle/inclusion body myopathy, PDB, and frontotemporal dementia
      (FTD) [IBMPFD, OMIM #605382]. Sequencing of Valosin-containing protein (VCP), the
      gene associated with IBMPFD, did not identify mutations. We have excluded linkage
      to the known loci for limb-girdle type of myopathy and bone disease and excluded
      several candidate genes. Elucidation of the novel molecular basis of this
      disorder may provide valuable links between bone, collagen and muscle, and
      targeted therapeutic options.

PMID- 16419138
TI  - Magnetic-dipolar-interaction-induced self-assembly affords wires of hollow
      nanocrystals of cobalt selenide.

PMID- 16419139
TI  - Bis(calixcrown)tetrathiafulvalene receptors.
AB  - A new class of electroactive receptors has been synthesized, built by covalent
      association of five subunits: two calixarene platforms for spatial organization,
      two polyether 3D cavities for cation binding, and one electroactive TTF unit to
      probe the complexation event. Sodium complexation induces rigidification of the
      molecular assembly, as shown by 1H NMR titration and single-crystal X-ray
      crystallographic studies on free receptor 14 and a corresponding complex with two
      bound sodium atoms per receptor (15-(NaPF6)2). The calixarene units in these
      receptors change from a pinched cone conformation in the free ligand to a
      symmetrical cone in the complex. Cyclovoltammetric studies validated the
      electrochemical recognition concept of these five-member assemblies.

PMID- 16419140
TI  - New cyanine-oligonucleotide conjugates: relationships between chemical structures
      and properties.
AB  - Because the influence of the chemical structure of monomethine cyanine-oligo-2'
      deoxyribonucleotide (ODN) conjugates on their binding and fluorescence properties
      has remained largely undetermined, we synthesized and studied a wide range of
      conjugates with various structural patterns. Different cyanine dyes such as
      thiocyanine, quinocyanine, and thiazole orange isomers were obtained. In the case
      of unsymmetrical cyanines, the linker was attached to either the quinoline or the
      benzothiazole nucleus. The influence of the ODN counterpart was evaluated by
      linking the cyanines to the 5'-end or to an internucleotidic phosphate. In the
      first case, the influence of neighboring nucleic bases was studied, whereas in
      the second, the stereochemical configuration at the phosphorus atom bearing the
      cyanine was investigated. We report here on relationships between the structures
      of the dyes and conjugates and some of their properties, such as the stability
      and fluorescence changes observed on their hybridization with the target
      sequence. This study provides useful information towards the design of ODN
      cyanine conjugates.

PMID- 16419141
TI  - The interaction of heteroaryl-acrylates and alanines with phenylalanine ammonia
      lyase from parsley.
AB  - Acrylic acids and alanines substituted with heteroaryl groups at the beta
      position were synthesized and spectroscopically characterized (UV, HRMS, (1)H
      NMR, and (13)C NMR spectroscopy). The heteroaryl groups were furanyl, thiophenyl,
      benzofuranyl, and benzothiophenyl and contained the alanyl side chains either at
      the 2- or 3-positions. While the former are good substrates for phenylalanine
      ammonia-lyase (PAL), the latter compounds are inhibitors. Exceptions are thiophen
      3-yl-alanine, a moderate substrate and furan-3-yl-alanine, which is inert.
      Possible reasons for these exceptions are discussed. Starting from racemic
      heteroaryl-2-alanines their D-enantiomers were prepared by using a
      stereodestructive procedure. From the heteroaryl-2-acrylates, the L-enantiomers
      of the heteroaryl-2-alanines were prepared at high ammonia concentration. These
      results can be best explained by a Friedel-Crafts-type electrophilic attack at
      the aromatic part of the substrates as the initial step of the PAL reaction.

PMID- 16419142
TI  - Synthesis, characterization, and folding behavior of beta-amino acid derived
      polyisocyanides.
AB  - Helical polymers of isocyanopeptides derived from beta-amino acids have been
      synthesized and their architectures have been studied in detail. Similar to their
      alpha-amino acid analogues, the helical conformation in these macromolecules is
      stabilized by internal hydrogen-bonding arrays along the polymeric backbone.
      Unexpectedly, the flexibility of the beta-peptide side arms results in a
      rearrangement of the initial macromolecular architecture, leading to a more
      stable helical structure possessing a better defined hydrogen-bonding pattern, as
      was concluded from IR and temperature-dependent circular dichroism studies. Based
      on these results we propose a dynamic helical model for the beta-amino acid
      derived polyisocyanopeptides; this model is in contrast to the kinetically stable
      helical macromolecules that are formed upon polymerization of alpha-amino acid
      based isocyanopeptides.

PMID- 16419143
TI  - (14)N NMR and two-dimensional suspension (1)H and (13)C HRMAS NMR spectroscopy of
      ionic liquids immobilized on silica.
AB  - A variety of popular ionic liquids have been synthesized and characterized,
      including by optimized (14)N NMR spectroscopy of the neat and dissolved ionic
      liquids. Ionic liquids incorporating Si(OEt)(3) groups have been immobilized on
      silica in a well-defined manner with the imidazolium moiety remaining intact.
      This has been proved by optimized one- and two-dimensional (1)H and (13)C HRMAS
      NMR spectroscopy of the materials suspended in suitable solvents.

PMID- 16419144
TI  - A practical ruthenium-catalyzed cleavage of the allyl protecting group in amides,
      lactams, imides, and congeners.
AB  - A convenient methodology for the deprotection of N-allylic amide-like moieties
      was developed. The first examples accounting for the ruthenium-catalyzed
      deallylation of amides, lactams, imides, pyrazolidones, hydantoins, and
      oxazolidinones have been achieved by the sequential use of Grubbs carbene
      (isomerization step) and RuCl(3) (oxidation step). A variety of substrates,
      including enantiopure multifunctional beta- and gamma-lactams, can be employed.

PMID- 16419146
TI  - A new method to determine electrostatic potential around a macromolecule in
      solution from molecular wave functions.
AB  - The three-dimensional reference interaction site model integral equation theory
      (3D-RISM) combined with the ab initio molecular orbital method (3D-RISM-SCF) is
      applied to a solvated macromolecular system. The solvation structure around a
      solute molecule is obtained from the 3D-RISM integral equation under the
      electrostatic potential of the solute molecule, calculated by the ab initio
      molecular orbital theory. The electrostatic potential should be calculated on
      each grid point in the three-dimensional real space. Therefore, the calculation
      of the electrostatic potential is the most time consuming part in this method. In
      this article, we propose a new procedure to save the computational cost for
      calculating the electrostatic potential and the solvated fock matrix. The
      strategy of this procedure is to evaluate the electrostatic potential and the
      solvated fock matrix in different ways, depending on the distance between solute
      and solvent. Inside the repulsive cores of solute atoms, it is possible to avoid
      the calculation of electrostatic potential and solvated Fock matrix by assuming
      the potential to be infinity. In the region sufficiently far from solute, they
      are evaluated classically by putting the effective point charge on each atom. In
      the intermediate region, the electrostatic potential is evaluated directly by
      integrating the molecular orbitals of the solute molecule. The electronic
      structure and the energy gradient of Methionine-Enkephalin and solvation
      structure are estimated by using this procedure in aqueous solution, and are
      compared with the results from other procedures. The results are compared also
      with those from the continuum model.

PMID- 16419145
TI  - Myocardium distribution of sertindole and its metabolite dehydrosertindole in
      guinea-pigs.
AB  - Sertindole, like other atypical antipsychotics, has been shown to increase the
      action potential duration and QT interval in a concentration dependent manner, in
      in vitro electrophysiological studies. However, this does not always translate
      into increased duration of the QT interval, increased risk of torsade de pointes
      or sudden death in clinical practice. The reasons for these apparent
      discrepancies are unclear and many studies have underscored the importance of the
      interpretation of in vitro electrophysiological data in the context of other
      pharmacodynamic (e.g. cardiac ion channels target, receptor affinity) and
      pharmacokinetic parameters (total plasma drug concentration and drug
      distribution). To address the possible relevance of the concentrations used in
      experimental studies, the myocardium distribution of sertindole and its
      metabolite was determined after single and repeated intraperitoneal
      administration to guinea-pigs. The data suggest that the plasma concentration
      appears to predict the concentration in the myocardium and that the myocardium
      concentrations of sertindole are 3.1 times higher than plasma concentrations.
      Using these data, the relevance of in vitro electrophysiological studies to
      clinical plasma concentrations has been appraised.

PMID- 16419147
TI  - New force field for calcium binding sites in annexin-membrane complexes.
AB  - For accurate classical molecular dynamics (MD) simulations of the calcium
      mediated bound complexes of annexin and membrane we have developed new force
      field parameters correctly describing the interaction of the Ca ion with its
      environment. We have used quantum chemical calculations to investigate the
      potential energy surface experienced by the Ca ion within the three different
      binding sites found in domain 1 of annexin V (ANX V/1). Based on these
      calculations we were able to quantify the charge polarization of atoms within the
      binding sites, and to determine the geometry and force constants of harmonic
      restraints between the Ca ion and its coordinating oxygen atoms. Harmonic
      restraints were introduced to compensate for the deviations between the quantum
      mechanical potential energy surface and that of the classical force field. Our
      analysis has shown that using the refined force field for the Ca binding sites
      enables long-time MD simulations that conserve the initial structure of ANX V/1
      significantly better than MD simulations using the standard force field.

PMID- 16419148
TI  - Relativistic correlating basis sets for lanthanide atoms from Ce to Lu.
AB  - Contracted Gaussian-type function (CGTF) sets for the description of the 4f
      subshell correlation and of the 6s and 5d subshell correlation are developed for
      lanthanide atoms from Ce to Yb. Also prepared are basis sets for the 5d orbitals,
      which are vacant in the ground states of most lanthanide atoms but are essential
      in molecular environments. In addition, correlating CGTF sets for the 4f subshell
      correlation are supplemented for the Lu atom. A segmented contraction scheme is
      employed for their compactness and efficiency. Contraction coefficients and
      exponents are determined by minimizing the deviation from accurate natural
      orbitals generated from configuration interaction calculations that include
      relativistic effects through the third-order Douglas-Kroll approximation. All
      electron and model core potential calculations with the present correlating sets
      are performed on the ground state of the diatomic CeO molecule. The calculated
      spectroscopic constants are in good agreement with experimental values.

PMID- 16419149
TI  - Endothelial adhesion of synchronized gastric tumor cells changes during cell
      cycle transit and correlates with the expression level of CD44 splice variants.
AB  - AIM: To study adhesion capacity and CD44 expression of human gastric
      adenocarcinoma MKN45 cells at different stages of a first cell cycle. METHODS:
      MKN45 cells were synchronized by aphidicolin and assayed for adhesion to an
      endothelial cell (HUVEC) monolayer. Surface expression of CD44 and CD44 splice
      variants on MKN45 cells was evaluated by flow cytometry. Functional relevance of
      CD44 adhesion receptors was investigated by blocking studies using anti CD44
      monoclonal antibodies or by hyaluronan digestion. RESULTS: Adhesion of MKN45 to
      HUVEC was increased during G2/M transit, after which adhesion returned to
      baseline levels with cell cycle completion. In parallel, CD44 splice variants
      CD44v4, CD44v5, and CD44v7 were all up-regulated on MKN45 during cell cycle
      progression with a maximum effect in G2/M. The function of CD44 surface receptors
      was assessed with specific receptor blocking monoclonal antibodies or removal of
      hyaluronan by digestion with hyaluronidase. Both strategies inhibited tumor cell
      adhesion to HUVEC by nearly 50%, which indicates that MKN45-HUVEC-interaction is
      CD44 dependent. CONCLUSION: CD44 expression level is linked to the cell cycle in
      gastrointestinal tumor cells, which in turn leads to cell cycle dependent
      alterations of their adhesion behaviour to endothelium.

PMID- 16419150
TI  - Preliminary study on proteomics of gastric carcinoma and its clinical
      significance.
AB  - AIM: To explore the preliminary identification of serum protein pattern models
      that may be novel potential biomarkers in the detection of gastric cancer.
      METHODS: A total of 130 serum samples, including 70 from patients with gastric
      cancer and 60 from healthy adults, were detected by surface-enhanced laser
      desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The
      data of spectra were analyzed by Biomarker Patterns Software (BPS). Thirty serum
      samples of gastric cancer patients and 30 serum samples of healthy adults were
      grouped into the training group to build models, and the other 70 samples were
      used to test and evaluate the models. The samples of the test group were judged
      only with their peaks' height and were separated into cancer group or healthy
      control group by BPS automatically and the judgments were checked with the
      histopathologic diagnosis of the samples. RESULTS: Sixteen mass peaks were found
      to be potential biomarkers with a significant level of P< 0.01. Among them, nine
      mass peaks showed increased expression in patients with gastric cancer. Analyzed
      by BPS, two peaks were chosen to build the model for gastric cancer detection.
      The sensitivity, specificity, and accuracy of the model were 90%, 36/40, 86.7%,
      26/30, and 88.6%, 62/70, respectively, which were greatly higher than those of
      clinically used serum biomarkers CEA (carcinoembryonic antigen), CA19-9 and CA72
      4. Stage I/II gastric cancer samples of the test group were all judged correctly.
      CONCLUSION: The novel biomarkers in serum and the established model could be
      potentially used in the detection of gastric cancer. However, large-scale studies
      should be carried on to further explore the clinical impact on the model.

PMID- 16419151
TI  - Capsaicin-induced cell death in a human gastric adenocarcinoma cell line.
AB  - AIM: Capsaicin, a pungent ingredient found in red pepper, has long been used in
      spices, food additives, and drugs. Cell death induced by the binding of capsaicin
      was examined in a human gastric adenocarcinoma cell line (AGS cells). METHODS: By
      using XTT-based cytotoxicity assay, flow cytometry using the TUNEL method, and
      quantitation of DNA fragmentation, both cell death and DNA fragmentation were
      detected in AGS cells treated with capsaicin. By using Western blotting methods,
      capsaicin reduced the expression of Bcl-2, the antiapoptotic protein, in AGS
      cells in a concentration-dependent manner. RESULTS: After incubation of AGS cells
      with capsaicin for 24 h, cell viability decreased significantly in a dose
      dependent manner. After incubation of AGS cells with capsaicin for 24 h,
      apoptotic bodies also significantly increased, and were again correlated with the
      dose of capsaicin. When the concentration of capsaicin was 1 mmol/L, the amount
      of DNA fragments also increased. Similar results were also in the lower traces.
      CONCLUSION: These results suggest that capsaicin-induced cell death might be via
      a Bcl-2 sensitive apoptotic pathway. Therefore, capsaicin might induce protection
      from gastric cancer.

PMID- 16419152
TI  - Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human
      hepatocellular carcinoma cell lines via inhibition of NF kappa B.
AB  - AIM: To investigate the reduction of cell viability in human hepatocellular
      carcinoma (HCC) cell lines induced by inhibition of nuclear factor kappa B (NF
      kappa B). METHODS: HLE, SKHep1, and HepG2 were incubated and E3330 was used to
      compare the stimulation of some chemotherapeutic drugs with that of TNF family,
      Fas ligand, TNF alpha and TNF-related apoptosis-inducing ligand (TRAIL) at the
      point of the reduction of cell viability by inhibiting NF kappa B. RESULTS: E3330
      decreased NF kappa B levels in HLE cells stimulated by TNF and TRAIL. The
      cytotoxicity of the combination of TRAIL, TNF alpha, Fas ligand, and E3330
      increased synergistically in a dose-dependent manner compared to either E3330
      alone in all HCC cell lines by MTT assay. However, the combination of some
      chemotherapeutic drugs and E3330 did not decrease the cell viability. CONCLUSION:
      Inhibition of NF kappa B sensitizes human HCC cell lines to TNF-mediated
      apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful
      potential therapeutic tool in the treatment of human HCC.

PMID- 16419153
TI  - Classification tool for the systematic histological assessment of hepatocellular
      carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver.
AB  - AIM: To design a classification tool for the histological assessment of
      hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative
      nodules (MRN) in cirrhotic liver. METHODS: Two hundred and twelve hepatocellular
      nodules (106 HCC; 74 MRN; 32 DN) were assessed systematically, quantitatively,
      and semiquantitatively as appropriate for 10 histological features that have been
      described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic
      livers. The data were analyzed by multiple correspondence analysis (MCA).
      RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological
      evaluation as well as the individual histological variables, in a "malignancy
      scale". Based on the MCA data representation, we created a classification tool,
      which categorizes an individual nodular lesion as MRN, DN, or HCC based on the
      balance of all histological features (i.e., vascular invasion, capsular invasion,
      tumor necrosis, tumor heterogeneity, reticulin loss, capillarization of
      sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The
      classification tool classified most (83%) of a validation set of 47 nodules in
      the same way as the routine histological assessment. No discrepancies were
      present for DN and MRN between the routine histological assignment and the
      classification tool. Of 25 HCC assigned by routine assessment in the validation
      set, 8 were assigned to the DN category by the classification tool. CONCLUSION:
      We have designed a classification tool for the histological assessment of HCC and
      its putative precursors in cirrhotic liver. Application of this tool
      systematically records histological features of diagnostic importance in the
      evaluation of small HCC.

PMID- 16419155
TI  - Percutaneous ethanol injection, radiofrequency and their combination in treatment
      of hepatocellular carcinoma.
AB  - AIM: To evaluate the therapeutic effect and the indication of percutaneous
      ethanol injection (PEI), radiofrequency ablation (RFA) and their combination in
      treatment of hepatocellular carcinoma (HCC). METHODS: Two hundred and fifty-five
      patients with HCC received treatment of PEI, RFA or their combination. Group 1 (<
      3 cm in diameter, n=85) was treated with PEI, group 2 (< 3 cm in diameter, n=153)
      with RFA. Group 3 (> 3 cm in diameter, n=86) was divided into two groups. Group
      3a (n=34) was treated with RFA, while group 3b (n=52) was treated with RFA for 2
      wk after transcatheter arterial chemoembolization or PEI. Contrast-enhanced
      sonography was performed for 61 patients before and after RFA. Liver function and
      serum alpha-fetoprotein (AFP) were measured for all patients. Changes of the
      lesions on ultrasound and contrast-enhanced CT/MRI were evaluated for assessing
      the therapeutic responses. The 1-, 2-, 3- and 5-year survival rates were recorded
      after treatment. RESULTS: In group 1, the complete necrosis rate of lesions after
      1 mo was 77.6% (66/85). The level of AFP declined conspicuously after 1 mo. The 1
      , 2-, 3- and 5-year survival rate after treatment was 80.0% (52/65), 60.4%
      (32/53), 52.5% (21/40) and 33.3% (7/21), respectively. In group 2, the complete
      necrosis rate of lesions after 1 moh was 92.2% (141/153). The level of AFP
      decreased conspicuously after 1 mo. The 1-, 2-, 3- and 5-year survival rate after
      treatment was 94.6% (88/93), 73.2% (52/71), 63.5% (33/52) and 46.4% (13/28),
      respectively. In group 3a, the complete necrosis rate of lesions after 1 mo was
      23.5% (8/34). AFP dropped down to the normal level in only one patient after 1
      mo. The 1-, 2- and 3-year survival rate after treatment was 47.6% (10/21), 42.9%
      (6/14) and 27.3% (3/11), respectively. Only one patient was still alive after 5
      years. In group 3b, the complete necrosis rate of lesions after 1 mo was 57.7%
      (30/52). The level of AFP decreased after 1 mo. The 1-, 2-, 3- and 5-year
      survival rate after treatment was 68.6% (24/35), 46.2% (12/26), 36.8% (7/19) and
      27.3% (3/11), respectively. CONCLUSION: The therapeutic effect of RFA on small
      HCC is better than that of PEI. Small HCC is the optimal indication of RFA. For
      recurrent HCC (diameter > 3 cm), the combined treatment of RFA and PEI/ACE should
      be used.

PMID- 16419154
TI  - Mechanism of metastasis by membrane type 1-matrix metalloproteinase in
      hepatocellular carcinoma.
AB  - AIM: To investigate the precise role of membrane type 1-matrix metalloproteinase
      (MT1-MMP) in hepatocellular carcinoma (HCC) metastasis. METHODS: Human HCC cells
      Hep3B with overexpression of MT1-MMP were established by stable transfection, and
      compared with control cells carrying the empty vector. Cells were examined in
      vivo for their differences in the metastatic ability of athymic nude mice, and
      analyzed in vitro for their differences in invasion ability by invasion chamber
      coated with Matrigel, adhesion towards collagen I and migration through culture
      chamber. Cell proliferation and apoptosis in adherent and suspension status were
      evaluated by MTT and flow cytometry analysis. RESULTS: We found that
      overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice
      with orthotopic implantation of HCC cells (incidence of 100% [MT1-MMP
      transfectants] vs 40% [vector control transfectants], P<0.05). MT1-MMP could also
      enhance cell invasion through Matrigel (107.7 vs 39.3 cells/field, P<0.001),
      adhesion towards matrix (0.30 vs 0.12 absorbance unit at 540 nm, P<0.001), cell
      migration (89.3 vs 39.0 cells/field, P<0.001), and cell proliferation (24.3 vs
      40.5 h/doubling, P<0.001). We also observed that MT1-MMP supported cell survival
      (71.4% vs 23.9%, P<0.001) with reduced apoptosis (43.7% vs 51.0%, P<0.05) in an
      attachment-free environment. CONCLUSION: MT1-MMP overexpression could enhance
      metastasis. In addition to its active role in matrix degradation during tumor
      invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment,
      which is important during metastasis when cells enter the circulation.

PMID- 16419156
TI  - Overexpression of cyclooxygenase-2 in human HepG2, Bel-7402 and SMMC-7721
      hepatoma cell lines and mechanism of cyclooxygenase-2 selective inhibitor
      celecoxib-induced cell growth inhibition and apoptosis.
AB  - AIM: To investigate the cyclooxygenase-2 (COX-2) expression level in human HepG2,
      Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2
      selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis.
      METHODS: Hepatoma cells were cultured and treated with celecoxib. Cell in situ
      hybridization (ISH) and immunocytochemistry were used to detect COX-2 mRNA and
      protein expression. Proliferating cell nuclear antigen and phosphorylated Akt
      were also detected by immunocytochemistry assay. Cell growth rates were assessed
      by 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium (MTT) bromide
      colorimetric assay. Celecoxib-induced cell apoptosis was measured by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and flow
      cytometry (FCM). The phosphorylated Akt and activated fragments of caspase-9,
      caspase-3 were examined by Western blotting analysis. RESULTS: Increased COX-2
      mRNA and protein expression were detected in all three hepatoma cell lines.
      Celecoxib could significantly inhibit cell growth and the inhibitory effect was
      in a dose- and time-dependent manner evidenced by MTT assays and morphological
      changes. The apoptotic index measured by TUNEL increased correspondingly with the
      increased concentration of celecoxib and the reaction time. With 50 micromol/L
      celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC
      7721 cells was 25.01+/-3.08%, 26.40+/-3.05%, and 30.60+/-2.89%, respectively.
      Western blotting analysis showed remarkable activation of caspase-9, caspase-3
      and dephosphorylation of Akt (Thr(308)). Immunocytochemistry also showed the
      reduction of PCNA expression and phosphorylation Akt (Thr(308)) after treatment
      with celecoxib. CONCLUSION: COX-2 mRNA and protein overexpression in HepG2, Bel
      7402 and SMMC-7721 cell lines correlate with the increased cell growth rate.
      Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains
      in a dose- and time-dependent manner.

PMID- 16419157
TI  - Avidin-biotin system pretargeting radioimmunoimaging and radioimmunotherapy and
      its application in mouse model of human colon carcinoma.
AB  - AIM: To evaluate the multi-step pretargeting radioimmunoimaging (RII) and
      radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma with avidin
      biotin system labeled with (153)Sm. METHODS: Two- and three-step strategies for
      avidin-biotin system pretargeting techniques were established. In a three-step
      procedure, human colon carcinoma bearing nude mice were first injected with
      biotinylated monoclonal antibody (McAb-Bt) followed by cold avidin (Av) 48 h
      later and then (153)Sm-DB(2) 24 h thereafter; whereas the two-step procedure
      consisted of injection of (153)Sm-SA 48 h after pretargeting with biotinylated
      anti-CEA monoclonal antibody (CEA McAb-Bt). SPECT imaging and biodistribution
      were performed at 4, 24, 48, or 72 h after injection of (153)Sm-labeled
      compounds. Five groups of nude mice subcutaneously grafted with human colon
      carcinoma were treated 3 d after grafting. One group received the injection with
      100 microg CEA McAb-Bt followed by cold avidin (80 microg) after 2 d and 11.1 MBq
      (153)Sm-DB(2) after 1 d. Four control groups were treated respectively with 11.1
      MBq (153)Sm-CEA McAb, 11.1 MBq (153)Sm-nmIgG, 11.1 MBq (153)Sm-DB(2), 100 microL
      normal saline. Toxicity was evaluated by changes of leukocyte count, and the
      efficacy by variation in tumor volume. Histological analyses of tumors were
      performed. RESULTS: The three-step procedure allowed faster blood clearance and
      yielded higher tumor blood ratios (5.76 at 4 h and 12.94 at 24 h) of the (153)Sm
      DB(2). The tumor was clearly visualized at 4 h in gamma-imaging after the
      injection of (153)Sm-DB(2), while a significant accumulation of (153)Sm-SA in the
      tumor was observed only 24 h after the injection and tumor blood ratios at 4 and
      24 h were 1.00 and 2.03, respectively, in the two-step procedure. Pretargeting
      RIT and (153)Sm-CEA McAb had a strong tumor-inhibiting effect. The tumor
      inhibitory rate was 80.67% and 78.44%, respectively, five weeks after therapy.
      Histopathological evidence also indicated radioactive damage in tumor tissues as
      necrosis of tumor cells, while in the other organs such as liver and kidney no
      radioactive damage was observed. Leukocyte counts showed significant decrease
      after treatment in groups of (153)Sm-CEA McAb and (153)Sm-nmIgG. CONCLUSION: The
      two kinds of pretargeting strategies can elevate the target-to-nontarget ratio,
      decrease the blood background and shorten the imaging time compared to (153)Sm
      CEA McAb. Three-step pretargeting RIT is as efficient as (153)Sm-CEA McAb, but
      markedly less toxic. This study provides experimental evidence for the clinical
      application of pretargeting RII and RIT.

PMID- 16419158
TI  - Classifying genotype F of hepatitis B virus into F1 and F2 subtypes.
AB  - AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F
      and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F
      (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and
      Venezuela, and their full-length sequences were determined. Phylogenetic analysis
      was carried out among them along with HBV isolates previously reported. RESULTS:
      Seven of them clustered with reported HBV/F isolates in the phylogenetic tree
      constructed on the entire genomic sequence. The remaining four flocked on another
      branch along with three HBV isolates formerly reported as genotype H. These seven
      HBV isolates, including the four in this study and the three reported, had a
      sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by >
      13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked
      genomic divergence, falling just short of > 8% separating the seven genotypes,
      these seven HBV/F isolates were classified into F2 subtype and the former seven
      into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences
      among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136
      representing the other six genotypes (A-E and G), two clusters separated by
      distinct genetic distances emerged. CONCLUSION: Based on these analyses,
      classifying HBV/F isolates into two subtypes (F1 and F2) would be more
      appropriate than providing them with two distinct genotypes (F and H).

PMID- 16419159
TI  - Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and
      pathologic sequelae of colonization.
AB  - AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis.
      METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients
      were enrolled in this study. Mucosal biopsy samples were obtained from the
      gastric antrum and GU site during endoscopy. Samples were used in in situ
      stimulation for 48 h in the presence of 10 microg/mL phytohemagglutinin-P (PHA),
      histological examination, and Helicobacter pylori (H pylori) culture. IL-17 and
      IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA
      expression was analyzed by reverse transcriptase-polymerase chain reaction (RT
      PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a
      line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after
      AGS cells were co-cultured with H pylori strain 26,695 or recombinant human (rh)
      IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be H
      pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori
      strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral
      mucosal tissues from H pylori-positive patients contained significantly (H pylori
      positive NU patients: median 467 pg/mg/protein, range 53-2,499; H pylori-negative
      NU patients: median 104 pg/mg/protein, range 16-312, P< 0.0005) higher levels of
      IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were
      significantly (ulcer site: median 1,356 pg/mg/protein, range 121-1,3730; antrum:
      median 761 pg/mg/protein, range 24-7,620, P< 0.005) higher than those at distant
      sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL
      17 mRNA expression in all samples whereas those from the antrum of the H pylori
      negative controls showed no detectable expression. A significant correlation was
      seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62, P<
      0.0001; antrum: r = 0.61, P< 0.0001) in GU patients. RhIL-17 and H pylori strain
      26,695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17 may play
      an important role in the inflammatory response to H pylori colonization, and may
      ultimately influence the outcome of H pylori-associated diseases that arise
      within the context of gastritis.

PMID- 16419160
TI  - Expression of matrix metalloproteinases and tissue inhibitor metalloproteinases
      increases in X-irradiated rat ileum despite the disappearance of CD8a T cells.
AB  - AIM: To investigate their expression and activity in the rat ileum after exposure
      to ionizing radiation along with that of the cellular effectors and molecular
      mediators involved in the regulation of MMPs. METHODS: Rats were exposed to a
      single 10-Gy dose of X-rays delivered to the abdomen. A combination of methods,
      such as zymography, immunohistochemistry and real time reverse transcriptase
      polymerase chain reaction, were used to localize and quantify MMPs and the
      molecules involved in MMP activating and inhibitory pathways
      (plasmin/plasminogen, TIMPs), CD8+, as well as inflammatory (interleukin (IL)
      1beta, IL-8, tumor necrosis factor-alpha, TNF-alpha) and fibrogenic mediators
      (transforming growth factor-beta1-3) within ileal tissue at 1, 3, and 7 d after
      irradiation. RESULTS: A marked increase in MMP-2 and -14 mRNA and protein levels
      associated with an increased activity of MMP-2 was observed in irradiated ileal
      tissue. MMP-2 and -14 expression was mainly observed in inflammatory, epithelial,
      and mesenchymal cells, whereas a slight increase in MMP-3 expression was detected
      in the few infiltrating macrophages at d 1 after irradiation. Conversely, MMP-1, 
      7, and -9 mRNA levels were not found to be affected by abdominal irradiation.
      Irradiation was found to induce disappearance of CD8+ cells. Furthermore, we have
      observed that TNF-alpha and IL-1beta protein levels increased 6 h after
      irradiation, whereas those of IL-8 only increased after 3 d and was concomitant
      with neutrophil infiltration. In addition, the expressions of molecules involved
      in MMP activating and inhibitory pathways (urokinase-type plasminogen activator
      and tissue-type plasminogen activator; TIMP-1, TIMP-2, and plasminogen activator
      inhibitor-1) were found to be increased after abdominal irradiation. CONCLUSION:
      This study showed that abdominal irradiation induces an acute remodeling of the
      ileum associated with an increased expression of MMPs and TIMPs that do not
      involve CD8+ T cells but involve mesenchymal and epithelial cells, although to a
      lesser extent, and probably even soluble inflammatory and fibrogenic mediators.

PMID- 16419161
TI  - Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor
      gamma, protects pancreas against acute cerulein-induced pancreatitis.
AB  - AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator
      activated receptor-gamma (PPARgamma) ligand, on the development of acute
      pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the
      pancreas. METHODS: AP was induced in rats by subcutaneous infusion of cerulein
      for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma
      lipase activity, interleukin-1beta (IL-1beta) and IL-10 were determined.
      Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and
      blood flow as well as pancreatic mRNA for IL-1beta and HSP70 were assessed in
      rats treated with pioglitazone alone or in combination with cerulein. RESULTS:
      Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated
      dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis
      (CIP) as demonstrated by the improvement of pancreatic histology, reduction in
      plasma lipase activity, plasma concentration of pro-inflammatory IL-1beta and its
      gene expression in the pancreas and attenuation of the pancreatitis-evoked fall
      in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein
      expression in the pancreas and this effect was enhanced by pioglitazone
      treatment. CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of
      this pioglitazone is multifactorial probably due to its anti-inflammatory
      activities, to the suppression of IL-1beta and to the overexpression of HSP70.
      PPARgamma ligands could represent a new therapeutic option in the treatment of
      AP.

PMID- 16419162
TI  - Distinct immune response induced by peptidoglycan derived from Lactobacillus sp.
AB  - AIM: To analyze the distinct immune responses induced by Lactobacillus
      peptidoglycan (PG). METHODS: BALB/c mice were intraperitoneally injected with PG
      once a day for three consecutive days. Peritoneal macrophage and splenocyte mRNA
      was extracted and the gene expression profile was studied using high-density
      oligonucleotide microarrays. Inhibitory effects of Lactobacillus PG on colon
      tumor tissue were studied in vitro and in vivo. RESULTS: The gene expression
      profiles revealed that the TLR-NF-kappaB; and Jak-STAT signaling pathways were
      highly activated. An inflammatory phenotype was induced when peritoneal
      macrophages were initially exposed to Lactobacillus PG and switched to a more
      complex phenotype when BALB/c mice were treated with three doses of Lactobacillus
      PG. A protective physiological inflammatory response was induced after three
      consecutive days of PG treatment. It was tending toward Th1 dominant immune
      response. Lactobacillus PG also appeared to induce a significant in vivo anti
      colon tumor effect. CONCLUSION: Lactobacillus PG is responsible for certain
      immune responses induced by Lactobacilli. Anti-tumor effects of Lactobacilli are
      likely to attribute to the activation of macrophages by PG expressed on the
      bacterial cell surface.

PMID- 16419163
TI  - Characterization of colonic dendritic cells in normal and colitic mice.
AB  - AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC)
      in the activation of pathogenic T cells in animal models of inflammatory bowel
      disease identify DC as important antigen presenting cells in the colon. However,
      very little is known about the properties of colonic DC. METHODS: Using
      immunohistochemistry, electron microscopy and flow cytometry we have
      characterized and compared colonic DC in the colon of healthy animals and
      interleukin-2-deficient (IL2(-/-)) mice that develop colitis. RESULTS: In the
      healthy colon, DC resided within the lamina propria and in close association with
      the basement membrane of colonic villi. Type 1 myeloid (CD11c(+), CD11b(+), B220(
      ), CD8alpha(-)) DC made up the largest (40-45%) population and all DC expressed
      low levels of CD80, CD86, and CD40, and had high endocytic activity consistent
      with an immature phenotype. In colitic IL2(-/-) mice, colonic DC numbers
      increased four- to five-fold and were localized within the epithelial layer and
      within aggregates of T and B cells. They were also many more DC in mesenteric
      lymph nodes (MLN). The majority (>85%) of DC in the colon and MLN of IL2(-/-)
      mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86,
      CD40, DEC 205, and CCR5 molecules and were of low endocytic activity consistent
      with mature DC. CONCLUSION: These findings demonstrate striking changes in the
      number, distribution and phenotype of DC in the inflamed colon. Their intimate
      association with lymphocytes in the colon and draining lymph nodes suggest that
      they may contribute directly to the ongoing inflammation in the colon.

PMID- 16419164
TI  - Hemodynamic and morphologic changes of peripheral hepatic vasculature in
      cirrhotic liver disease: a preliminary study using contrast-enhanced coded phase
      inversion harmonic ultrasonography.
AB  - AIM: To provide the useful information for the diagnosis of liver cirrhosis by
      observing the morphology of peripheral hepatic vessels and the hemodynamics of
      microbubble arrival time in these vessels. METHODS: Twenty-one subjects including
      5 normal volunteers and 16 patients (liver cirrhosis, n=10; chronic hepatitis,
      n=6) were studied by contrast-enhanced coded phase inversion harmonic sonography
      (GE LOGIQ 9 series) using a 6-8 MHz convex-arrayed wide-band transducer. The
      images of peripheral hepatic artery, portal and hepatic vein were observed in
      real-time for about 2 min after intravenous injection of Levovist. The time when
      microbubbles appeared in the peripheral vessels (microbubble arrival time) was
      also recorded. The morphologic changes of peripheral hepatic vasculature were
      classified as marked, slight, and no changes based on the regularity in caliber,
      course, ramification, and the delineation of vessels compared to normal subjects.
      RESULTS: The microbubble arrival time at peripheral artery, portal, and hepatic
      vein was shorter in cirrhotic patients than in chronic hepatitis patients and
      normal subjects. The marked, slight and no morphologic changes of peripheral
      hepatic vasculature found in 5 (5/6, 83.3%), 1 (1/6, 16.7%), and 0 (0/6, 0%)
      liver cirrhosis patients, respectively, and in 1 (1/10, 10%), 6 (6/10, 60%), and
      3 (3/10, 30%) chronic hepatitis patients, respectively. There was a significant
      difference between the two groups (P< 0.001). CONCLUSION: Evaluation of the
      hemodynamics and morphology of peripheral hepatic vasculature by contrast
      enhanced coded pulse inversion harmonic sonography can provide useful information
      for the diagnosis of liver cirrhosis.

PMID- 16419165
TI  - Imaging findings of biliary hamartomas.
AB  - AIM: To evaluate the imaging findings of biliary hamartomas (von Meyenburg
      complexes, VMCs) and discuss the differential diagnosis with other related
      diseases. METHODS: Imaging findings of biliary hamartomas on ultrasonography
      (US), computed tomography (CT), magnetic resonance imaging (MRI), MR
      cholangiopancreatography (MRCP)and hepatobiliary scintigraphy were
      retrospectively analyzed in six patients. RESULTS: On ultrasound images, five of
      the six cases showed multiple small hyper- and hypo-echoic lesions with comet
      tail echoes, especially when magnified by US with the usage of zoom function. In
      all the six cases, multiple tiny hypodense lesions less than 10 mm in diameter
      were revealed as scattered throughout the liver with no enhancement on CT. These
      tiny lesions were demonstrated to be hyper- and hypo-intensity on T2- and TI
      weighed images, respectively, in three patients who underwent MRI examinations.
      MRCP was performed in two patients, and clearly showed multiple tiny irregular-
      and round-shaped hyper-intensity lesions. MRCP and hepatobiliary scintigraphy
      showed normal appearances of intra- and extra-hepatic bile ducts in two and one
      patients, respectively. CONCLUSION: Imaging modalities are useful in the
      diagnosis and differential diagnosis of VMCs. A correct diagnosis might be
      obtained when typical imaging findings are present even without a histological
      confirmation.

PMID- 16419166
TI  - Distinction between short-segment Barrett's esophageal and cardiac intestinal
      metaplasia.
AB  - AIM: To investigate the roles of mucin histochemistry, cytokeratin 7/20 (CK7/20)
      immunoreactivity, clinical characteristics and endoscopy to distinguish short
      segment Barrett's esophageal (SSBE) from cardiac intestinal metaplasia (CIM).
      METHODS: High iron diamine/Alcian blue (HID/AB) mucin-histochemical staining and
      immunohistochemical staining were used to classify intestinal metaplasia (IM) and
      to determine CK7/20 immunoreactivity pattern in SSBE and CIM, respectively, and
      these results were compared with endoscopical diagnosis and the positive rate of
      gastroesophageal reflux disease (GERD) symptoms and H pylori infection. Long
      segment Barrett's esophageal and IM of gastric antrum were designed as control.
      RESULTS: The prevalence of type III IM was significantly higher in SSBE than in
      CIM (63.33% vs 23.08%, P< 0.005). The CK7/20 immunoreactivity in SSBE showed
      mainly Barrett's pattern (76.66%), and the GERD symptoms in most cases which
      showed Barrett's pattern were positive, whereas H pylori infection was negative.
      However, the CK7/20 immunoreactivity in CIM was gastric pattern preponderantly
      (61.54%), but there were 23.08% cases that showed Barrett's pattern. H pylori
      infection in all cases which showed gastric pattern was significantly higher than
      those which showed Barrett's pattern (63.83% vs 19.30%, P< 0.005), whereas the
      GERD symptoms in gastric pattern were significantly lower than that in Barrett's
      pattern (21.28% vs 85.96%, P< 0.005). CONCLUSION: Distinction of SSBE from CIM
      should not be based on a single method; however, the combination of clinical
      characteristics, histology, mucin histochemistry, CK7/20 immunoreactivity, and
      endoscopic biopsy should be applied. Type III IM, presence of GERD symptoms, and
      Barrett's CK7/20 immunoreactivity pattern may support the diagnosis of SSBE,
      whereas non-type III IM, positive H pylori infection, and gastric CK7/20
      immunoreactivity pattern may imply CIM.

PMID- 16419167
TI  - Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from
      different regions of Chile show a distinct geographic distribution.
AB  - AIM: To establish the most common vacA alleles in Helicobacter pylori (H pylori)
      strains isolated from Chilean patients and its relationship with gastritis and
      gastroduodenal ulcers. METHODS: Two hundred and forty five H pylori clinical
      isolates were obtained from 79 biopsies from Chilean infected patients suffering
      from gastrointestinal diseases. An average of 2-3 strains per patient was
      isolated and the vacA genotype was analyzed by PCR and 3% agarose
      electrophoresis. Some genotypes were checked by DNA sequencing. RESULTS: The most
      prevalent vacA genotype in Chilean patients was s1b m1 (76%), followed by s1a m1
      (21%). In contrast, the s2 m2 genotype was scarcely represented (3%). The s1b m1
      genotype was found most frequently linked to gastropathies (P<0.05) rather than
      ulcers. Ulcers were found more commonly in male and older patients. Curiously,
      patients living in cities located North and far South of Santiago, the capital
      and largest Chilean city, carried almost exclusively strains with the s1b m1
      genotype. In contrast, patients from Santiago and cities located South of
      Santiago carried strains with either one or both s1a m1 and s1b m1 genotypes.
      Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that
      Chilean s2 sequence was identical to those of Australian, American, and Colombian
      strains but quite different from those of Alaska and India. CONCLUSION:
      Differences in geographic distribution of the s and m vacA alleles in Chile and a
      relationship of s1b m1 genotype with gastritis were found. Sequence data in part
      support a hispanic origin for the vacA genotype. Asymmetric distribution of
      genotypes s1b m1 and s2 m2 recedes H Pylori strain distribution in Spain and
      Portugal.

PMID- 16419169
TI  - Apoptosis induced by nucleosides in the human hepatoma HepG2.
AB  - AIM: To investigate the apoptotic effects of nucleosides on the human hepatoma
      HepG2. METHODS: The nucleosides included inosine (I), cytidine (C), uridine (U),
      thymidine (T), adenosine (A), and guanosine (G). Cells were incubated by the
      mediums with or without nucleosides at 37 degree C in a 50 mL/L CO(2) humidified
      atmosphere. RESULTS: It was found that the cell viabilities were significantly
      decreased, when cells were treated with 30 mmol/L I, 30 mmol/L C, 30 mmol/L U, 30
      mmol/L T, 0.5 mmol/L A, and 0.5 mmol/L G after 12 h incubation (P< 0.05). About
      the apoptotic phenomenon, the cell percentages of sub-G(1) cells were
      significantly increased in the mediums containing nucleosides such as C, U, T, A,
      and G (P< 0.05). Furthermore, the caspase-3 activity was increased, when the
      cells were incubated with T (P< 0.05). The protein expressions of p53 and p21
      showed no difference in each group. To investigate the mechanism of apoptosis
      induced by nucleosides, it was found that the contents of soluble Fas ligand
      contents were increased in HepG2 cells following I, U, T, and A treatment (P<
      0.05). But, TNF-alpha and cytochrome c were undetectable. CONCLUSION: Thymidine
      may induce the apoptosis in HepG2, but the effective dosages and reactive time
      must be investigated in the future study. However, the apoptosis-inducing
      abilities of other nucleosides were still unclear in this study.

PMID- 16419168
TI  - Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells
      are heterogeneous and require high concentration of functional glucocorticoid
      receptors.
AB  - AIM: To determine how glucocorticoids (GCs) may affect the growth and
      chemosensitivity of common carcinoma cells. METHODS: The effect of dexamethasone
      (DEX) on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The
      function of GC receptors (GR) was assessed by MMTV reporter assay. Overexpression
      of GR was done by in vitro transfection and expression of a GR-expressing vector.
      Immunohistochemical stain of tissues and cells were done by PA1-511A, an anti-GR
      monoclonal antibody. RESULTS: DEX inhibited cell growth of four (MCF-7, MCF
      7/MXR1, MCF-7/TPT300, and HeLa), increased cisplatin cytotoxicity of one (SiHa),
      and decreased cisplatin cytotoxicity of two (H460 and Hep3B) cell lines. The GR
      content of the seven cell lines affected by DEX was significantly higher than
      those of the seven cell lines unaffected by DEX (5.2+/-2.5 x 10(4) sites/cell vs
      1.3+/-1.4 x 10(4) sites/cell, P = 0.005). Only two DEX-unresponsive cell lines
      (NPC-TW01 and NPC-TW04) contained high GR amounts in the range (1.9-8.1 x 10(4)
      sites/cell) of the seven DEX-responsive cell lines. The GR function of NPC-TW01
      and NPC-TW04, however, was found to be impaired. The importance of high cellular
      amount of GR in mediating DEX susceptibility of the cells was further exemplified
      by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR
      content and was unaffected by DEX before transfection of GR-expressing vector.
      Immunohistochemical studies of human cancer tissues showed that 5 of the 45
      (11.1%) breast cancer and 43 of the 85 (50.6%) non-small cell lung cancer had
      high GR contents at the ranges of the GC-responsive carcinoma cell lines.
      CONCLUSION: The growth and chemosensitivity of human carcinomas with high GR
      contents may be affected by GC. However, in light of the heterogeneous and even
      contradictive effects of GC on these cells, routine examination of GR contents of
      human carcinoma tissues may not be clinically useful until other markers that
      help predict the ultimate effect of GC on individual patients are identified.

PMID- 16419170
TI  - Effect of a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on
      invasion of human colorectal cancer cell line SL-174T.
AB  - AIM: To investigate the effect and mechanism of action of the nitric oxide
      synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on invasion
      and metastasis of human colorectal cancer cell line SL-174T. METHODS: Human
      colorectal cancer cell line SL-174T was cultured and treated separately with four
      different dosages of L-NAME for 72 h. Nitric oxide (NO) production was measured
      with Griess reagent. The effect of L-NAME on invasion and migration of SL-174T
      cells were evaluated by using Transwell chambers attached with polycarbonate
      filters and reconstituted basement membrane (Matrigel). RT-PCR was performed to
      determine the mRNA levels of matrix metalloproteinase-2 (MMP-2) and tissue
      inhibitor metalloproteinase-2 (TIMP-2). RESULTS: L-NAME could significantly
      inhibit NO production of SL-174T in a dose-dependent manner. After being treated
      for 72 h with 0.2, 0.4, 0.8, and 1.0 mmol/L L-NAME, respectively, the ability of
      the L-NAME treated SL-174T cells to invade the reconstituted basement membrane
      decreased significantly (t = 8.056, P< 0.05; t = 14.467, P< 0.01; t = 27.785, P<
      0.01; and t = 29.405, P< 0.01, respectively) and the inhibition rates were
      10.29%, 19.62%, 34.08%, and 42.23%, respectively. Moreover, L-NAME could inhibit
      migration of SL-174T cells, and the inhibition rates were 20.76%, 24.95%, 39.43%,
      and 46.85% for L-NAME at 0.2, 0.4, 0.8, and 1.0 mmol/L, respectively (t= 15.116,
      P< 0.01). In addition, after treatment with L-NAME, expression of MMP-2 mRNA was
      significantly decreased (t = 71.238, P< 0.01) and that of TIMP-2 mRNA was
      markedly increased (t = -13.020, P< 0.01). CONCLUSION: L-NAME exerts anti
      invasive and anti-metastatic effects on SL-174T cell line via downregulating MMP
      2 mRNA expression and upregulating TIMP-2 mRNA expression.

PMID- 16419173
TI  - Obese baby boomers at high risk of arthritis.

PMID- 16419171
TI  - Construction of prokaryotic expression system of TGF-beta1 epitope gene and
      identification of recombinant fusion protein immunity.
AB  - AIM: To insert the constructed TGF-beta(1) epitope gene into the el loop of C
      terminus of truncated hepatitis B core antigen to increase TGF-beta(1)
      antigenicity in its prokaryotic expression system and to identify immunity of the
      expressed recombinant protein in order to exploit the possibility for obtaining
      anti-TGF-beta(1) vaccine. METHODS: The TGF-beta(1) encoding epitope gene (the
      mature TGF-beta(1) from 78-109 amino acid residues, TGF-beta(1)(32)) was
      amplified by polymerase chain reaction from the recombinant pGEM-7z/ TGF
      beta(1)(32) vector. The HBcAg gene fragments (encoding HBcAg from 1-71 and 89-144
      amino acid residues) were amplified from PYTA1-HBcAg vector. The recombinant
      vector pGEMEX-1 was used to insert HBcAg1-71, TGF-beta(1)(32) and HBcAg89-144
      into restrictive endonuclease enzyme and ligated with T(4) ligase. The fusion
      gene fragments HBcAg1-71-TGF-beta(1)(32)- HBcAg89-144 were recloned to pET28a(+)
      and the DNA sequence was confirmed by the dideoxy chain termination method. The
      recombinant vector pET28a (+)/CTC was transformed and expressed in E. coli BL21
      (DE3) under induction of IPTG. After purification with Ni(+2)-NTA agarose resins,
      the antigenicity of purified protein was detected by ELISA and Western blot and
      visualized under electron microscope. RESULTS: Enzyme digestion analysis and
      sequencing showed that TGF-beta(1) epitope gene was inserted into the el loop of
      C-terminus of truncated hepatitis B core antigen. SDS-PAGE analysis showed that
      relative molecular mass (Mr) of the expressed product by pET28a (+)/CTC was Mr
      24,600. The output of the target recombinant protein was approximately 34.8% of
      the total bacterial protein, mainly presented in the form of inclusion body.
      Western blotting and ELISA demonstrated that the fusion protein could combine
      with anti-TGF-beta(1) polyclonal IgG but not with anti-HBcAg. The purity of
      protein was about 90% and the protein was in the form of self-assembling
      particles visualized under electron microscope. This fusion protein had good anti
      TGF-beta(1) antigenicity and could be used as anti-TGF-beta(1) vaccine.
      CONCLUSION: A recombinant prokaryotic expression system with high expression
      efficiency of the target TGF-beta(1) epitope gene was successfully established.
      The fusion protein is in the form of self-assembling particles and HBcAg can
      increase the antigenicity of TGF-beta(1). The expressed TGF-beta(1) epitope gene
      shows good immunogenicity and antigenicity.

PMID- 16419172
TI  - Treatment efficacy of radiofrequency ablation of 338 patients with hepatic
      malignant tumor and the relevant complications.
AB  - AIM: To investigate the treatment efficacy of radiofrequency ablation (RFA) of
      hepatic malignant tumor and the relevant complications. METHODS: A total of 338
      patients with 763 hepatic tumors underwent ultrasound-guided RFA (565
      procedures). There were 204 cases of hepatic cellular carcinoma (HCC) with 430
      tumors, the mean largest diameter was 4.0 cm. Of them, 48 patients (23.5%) were
      in stages I-II (UICC Systems) and 156 (76.5%) in stages III-IV There were 134
      cases of metastatic liver carcinoma (MLC), with 333 metastases in the liver, the
      mean diameter was 4.1 cm, the liver metastases of 96 patients (71.6%) came from
      gastrointestinal tract. Ninety-three percent of the 338 patients were treated
      using the relatively standard protocol. Crucial attention must be paid to monitor
      the abnormal changes in ultrasound images as well as the vital signs of the
      patients to find the possible hemorrhage and peripheral structures injury in
      time. The tumors were considered as ablated completely, if no viability was found
      on enhanced CT within 24 h or at 1 mo after RFA. These patients were followed up
      for 3-57 mo. RESULTS: The ablation success rate was 93.3% (401/430 tumors) for
      HCC and was 96.7% (322/333 tumors) for MLC. The local recurrence rate for HCC and
      MLC was 7.9% (34/430 tumors) and 10.5% (35/333 tumors), respectively. A total of
      137 patients (40.5%) underwent 2-11 times of repeated ablations because of tumor
      recurrence or metastasis. The 1st, 2nd, and 3rd year survival rate was 84.6%,
      66.6%, and 63.1%, respectively; the survival rate from 48 patients of I-II stage
      HCC was 93.7%, 80.4%, and 80.4%, respectively. The major complication rate in
      this study was 2.5% (14 of 565 procedures), which consisted of 5 hemorrhages, 1
      colon perforation, 5 injuries of adjacent structures, 2 bile leakages, and 1 skin
      burn. CONCLUSION: RFA, as a minimally invasive local treatment, has become an
      effective and relatively safe alternative for the patients of hepatic malignant
      tumor, even of advanced liver tumor, tumor recurrence, and liver metastases.
      Knowledge about possible complications and their control may increase the
      treatment efficacy and help to promote the use of RFA technique.

PMID- 16419174
TI  - Neuropsychiatric problems are abnormally prevalent in patients with RA and lupus.

PMID- 16419175
TI  - Certain occupations linked to AD, Parkinson's.

PMID- 16419176
TI  - Ovary removal may contribute to heart disease.

PMID- 16419177
TI  - Parkinson's drug may relieve fibromyalgia pain.

PMID- 16419178
TI  - Lung cancer can be diagnosed early.

PMID- 16419179
TI  - I periodically suffer from really annoying twitches in my lower eyelids. Is this
      a sign of a neurological disorder? These twitches start for no apparent reason,
      keep up for weeks, and then disappear.

PMID- 16419180
TI  - I have a heart condition. Is it OK for me to take Viagra (sildenafil)?

PMID- 16419181
TI  - Meeting pay-offs.

PMID- 16419182
TI  - Grants, clinical trials, and building research teams.

PMID- 16419183
TI  - Update on cervical screening.

PMID- 16419184
TI  - Management of cervical disease in HIV-infected women.

PMID- 16419185
TI  - Intrinsic fluorescence changes associated with apoptosis of human epithelial
      keratinocytes.

PMID- 16419186
TI  - Vibrational spectroscopy for identification of biochemical changes accompanying
      carcinogenesis and the formation of necrosis.

PMID- 16419187
TI  - Fluorescence spectroscopy as a diagnostic tool for detecting cervical pre-cancer.

PMID- 16419188
TI  - Psychoneuroimmunology, spirituality, and cancer.

PMID- 16419189
TI  - Cancer-related infertility.

PMID- 16419190
TI  - An integrated psycho-clinical model in the management of gynecologic cancers.

PMID- 16419191
TI  - Advances in cancer pain management in 2005.

PMID- 16419192
TI  - Native American Medicine: an introduction.

PMID- 16419193
TI  - Spiritual journey during and after cancer treatment.

PMID- 16419194
TI  - Mind-body tools: sustaining practitioners and patients.

PMID- 16419195
TI  - The relationship between physical factors, coping, and spirituality in cancer
      patients.

PMID- 16419196
TI  - Communication between patients and healthcare providers in oncology.

PMID- 16419197
TI  - Stress, spirituality, and cytokines in aging and cancer.

PMID- 16419198
TI  - Radical vaginal trachelectomy: a fertility-preserving option for young women with
      early stage cervical cancer.

PMID- 16419199
TI  - Sentinel lymph node identification (SLNI) in the management of conservative
      surgery in early cervical cancer: is it acceptable?

PMID- 16419200
TI  - Total pelvic exenteration: the reconstructive phase.

PMID- 16419201
TI  - Nerve sparing surgery in cervical cancer.

PMID- 16419202
TI  - Pretherapeutic laparoscopic staging of locally advanced cervical carcinomas:
      technique and results.

PMID- 16419203
TI  - FDG-PET in the evaluation of cervical cancer.

PMID- 16419204
TI  - 4th International Cervical Cancer Conference: update on PET and cervical cancer.

PMID- 16419205
TI  - 3D image based concepts in brachytherapy for cervical cancer.

PMID- 16419206
TI  - Cervical cancer status in Vietnam.

PMID- 16419207
TI  - Religious and cultural interpretation of illness in the Boston Haitian community
      and its impact on healthcare.

PMID- 16419209
TI  - A case-control study of human papillomavirus and cervical squamous
      intraepithelial lesions (SIL) in Harris County, Texas: differences among
      racial/ethnic groups.

PMID- 16419208
TI  - HPV and burden of cervical cancer in East Africa.

PMID- 16419210
TI  - Improving palliative care for cancer: a national and international perspective.

PMID- 16419211
TI  - Palliative care in advanced ovarian cancer patients with bowel obstruction.

PMID- 16419212
TI  - Spousal intimacy after cancer.

PMID- 16419213
TI  - Symptom control and communication issues in advanced cervical cancer.

PMID- 16419214
TI  - Provider influence in screening participation: does it matter?

PMID- 16419215
TI  - Global strategies for cervical cancer control in the 21st century.

PMID- 16419256
TI  - EUROECHO 9. Abstracts of the 9th Annual Meeting of the European Association of
      Echocardiography, Florence, Italy, 7-10 December 2005.

PMID- 16419216
TI  - Prospects for therapeutic HPV vaccines.

PMID- 16419257
TI  - Japan remembers Minamata.

PMID- 16419258
TI  - US big businesses struggle to cope with health-care costs.

PMID- 16419259
TI  - [Alzheimer 2005. Abstracts of the 8th Francophone Meeting on Alzheimer Disease
      and Related Syndromes. Saint-Etienne, France, 22-25 November 2005].

PMID- 16419260
TI  - Cumulative author and subject index for volumes 228-239 (2005).

PMID- 16419261
TI  - A plan for the future.

PMID- 16419262
TI  - Introduction: background, issues, and recommendations from the conference.

PMID- 16419263
TI  - The CONRAD/WHO Update 2000 colposcopy manual: how well is it working?

PMID- 16419264
TI  - Factors affecting the reproducibility and validity of colposcopy for product
      development: review of current literature.
AB  - Colposcopy has been adapted from cervical cytology screening as a tool to assess
      the tolerance of vaginal products in development for anti-infective and
      contraceptive indications. As the vagina is poorly enervated, symptoms do not
      correlate well with visual findings, which increases the importance of secondary
      assessment. Dysplasia screening has used biopsy liberally to verify the
      colposcopic diagnostic impression. The few studies that include correlative
      biopsy with colposcopy performed for product development are reviewed. A recent
      study of the reproducibility of two observations at a single visit by a single or
      two different physicians is discussed. The review points to magnification and
      experience of the observer as factors in improving the agreement between
      observations. Observers are more likely to agree on areas greater than 1 cm in
      diameter. Variation is reduced when fewer observers are used and they report
      findings as dichotomous or categorical data.

PMID- 16419265
TI  - Interpretation of genital findings in microbicide safety trials: review of the
      'Photo Atlas for Microbicide Evaluation'.
AB  - The Photo Atlas for Microbicide Evaluation was published in May 2002 for
      distribution among researchers to be used as a training or reference document
      during microbicide clinical trials. We have reviewed the contents of the Photo
      Atlas, including the interpretation and documentation of genital findings. The
      rationale for the categorization of genital lesions into different lesion types
      is also discussed. Efforts will continue to standardize colposcopy until more
      accurate and objective methods become available to assess the safety of candidate
      microbicides.

PMID- 16419266
TI  - Illumination, optics, and clinical performance of a hand-held magnified visual
      inspection device (AviScope): a comparison with colposcopy.
AB  - OBJECTIVE: Colposcopy is the reference standard for a visual inspection device in
      terms of illumination, optics, and clinical performance. A hand-held
      magnification device such as the AviScope, developed as an alternative to naked
      eye visual inspection with acetic acid, is also of interest as a low-cost, more
      portable alternative to a colposcope in low-resource settings within the context
      of cervical cancer prevention programs and for microbicides research. DESIGN: A
      performance comparison of the AviScope, visual inspection with acetic acid, and
      three colposcopes. METHODS: An analysis was carried out of the optics and
      illumination of the colposcopes and the AviScope prototype and of the evidence
      for the reproducibility and clinical accuracy of visual methods for
      histologically confirmed high-grade cervical intraepithelial neoplasia. Using the
      findings, the feasibility of increasing the performance and reducing the cost of
      a hand-held scope was examined. RESULTS: Published studies have found the
      AviScope to have slightly higher sensitivity than visual inspection with acetic
      acid (60.7 versus 55.7%, P < 0.05) without loss of specificity. Despite the
      variability among the colposcopes, the field of view, resolution, depth of field,
      magnification, and quality of the illumination beam pattern and spectral output
      exceeded that of the AviScope. The clinical sensitivity and specificity of
      colposcopy were higher than that of the AviScope. The availability of improved
      materials for optics and illumination suggests that a hand-held scope with
      enhanced performance is feasible. CONCLUSION: Although the performance of the
      AviScope prototype was suboptimal compared with the colposcopes, it appears
      possible to design a hand-held magnification device at a reasonable price with
      better optics and illumination.

PMID- 16419267
TI  - Portable colposcopy in low-resource settings.
AB  - Screening for cervical dysplasia is an important public health effort worldwide.
      In unscreened populations, the incidence of cervical cancer ranges between 2 and
      4% of the adult female population, whereas less than 0.1% of the screened
      population of Caucasian women has cervical cancer in the United States. In
      developing countries, cervical cytology is difficult to implement successfully
      because of the cost, cultural constraints, limited access to pathology services,
      etc. Bypassing cytology and going directly to colposcopy has been successfully
      implemented as a screening strategy for dysplasia in low resource settings. In
      this article we describe the development and utilization of a portable binocular
      colposcope that does not require electricity.

PMID- 16419268
TI  - Digital assessment of the reproductive tract (DART).
AB  - As the AIDS epidemic grows through heterosexual transmission, the development of
      women-controlled methods for defence against sexually transmitted infections and
      HIV, such as vaginally applied microbicides, is increasingly important. As part
      of the evaluation of the safety of all new topical microbicides, an evaluation of
      the cervix and vagina for any physical or mechanical effects of a potential agent
      is imperative. Traditionally, colposcopy has been used for such an evaluation. We
      introduce the concept of using a digital camera to assess the reproductive tract
      as a practical and effective means for studying the effects of microbicides on
      the vaginal and cervical epithelium. As much research on microbicides will be
      undertaken in areas with limited resources, digital assessment of the
      reproductive tract offers the advantage of portability, ease of use, durability,
      and accessibility. In addition, it allows digital data storage that can be used
      to review images, allow quality control, and provide an effective means to
      compare changes over time.

PMID- 16419269
TI  - Preclinical assessment of the proinflammatory potential of microbicide
      candidates.
AB  - The efficacy of a microbicide depends on the balance between its specific
      activity and its safety. The experience with nonoxynol-9, the first microbicide
      to be tested in clinical trials, provides a good example of a compound with high
      in-vitro activity and poor clinical performance, possibly because of
      underestimated local safety issues. In order to identify compounds that may
      induce epithelial toxicity and inflammation early in drug development, we have
      established a preclinical evaluation system based on the assessment of
      cytotoxicity, cytokine secretion, and tissue inflammatory reaction using a human
      vaginal cell line (VK-2/E6E7) and a refined rabbit vaginal irritation model.
      Evaluated through this system, nonoxynol-9 displayed high cytotoxicity and
      proinflammatory activity. VK-2 cells incubated for 6 h with nonoxynol-9 released
      significant amounts of IL-1, IL-6 and IL-8. Gels containing 2 and 4% nonoxynol-9,
      administered to female rabbits intravaginally for 3 days, induced a potent
      inflammatory reaction evidenced by high levels of IL-lb and CD3+ T cells in
      cervicovaginal lavages and a significant influx of CD4 and nuclear factor kappa B
      cells into mucosal and submucosal tissues. Interestingly, cervicovaginal
      epithelium exposed to nonoxynol-9 also showed high levels of active nuclear
      factor kappa B immunoreactivity. This combined, sequential, preclinical
      evaluation system based on VK-2 cells in culture and a refined rabbit vaginal
      irritation model represents a valuable tool to assess the local safety profile of
      anti-HIV microbicide candidates.

PMID- 16419270
TI  - The role of biopsy in vaginal microbicide development.
AB  - The technique of vaginal biopsy has been used to provide an objective assessment
      of inflammation in phase I vaginal microbicide studies conducted at Imperial
      College, London, since 1995. Biopsies are taken from the cervical aspect of the
      right fornix before product exposure at baseline, and from the cervical aspect of
      the left fornix at follow-up. We have found biopsy to be a simple, safe, and
      effective means of assessing genital inflammation in selected populations. Using
      this technique, inflammatory infiltrates can be characterized and agents with
      different modes of action can be compared. Vaginal biopsy is most useful in early
      phase I studies in sexually abstinent populations.

PMID- 16419273
TI  - Start talking.

PMID- 16419271
TI  - Guiding the vaginal microbicide trials with biomarkers of inflammation.
AB  - This article discusses cytokine patterns as potential biomarkers of vaginal
      inflammation, which are needed for the safety evaluation of topical microbicide
      products for the prevention of sexually transmitted HIV-1 infection. In order to
      be effective, the vaginal anti-HIV-1 microbicides should avoid proinflammatory
      responses that facilitate transepithelial viral penetration and replication. Pro
      inflammatory and anti-inflammatory cytokines play bi-directional roles in HIV-1
      pathogenesis, transmission, susceptibility and resistance. Previous research has
      shown that many of these key mediators of mucosal barrier function (e.g. IL-1, IL
      1 receptor antagonist, IL-6, TNF-alpha, TNF-receptor II, transforming growth
      factor beta, IL-10, IL-12, IL-8, macrophage inhibitory protein 1, etc.) can be
      detected in the vaginal secretions of healthy or infected individuals using non
      invasive sampling techniques. As part of two microbicide trials, we measured IL
      lalpha, IL-1beta, IL-1 receptor antagonist, TNF-alpha and IL-8 in 291
      cervicovaginal lavage samples obtained before product use and at the seventh and
      14th day after product use. We showed that vaginal formulations, temperature and
      matrix-specific factors in the vaginal fluids may interfere with cytokine
      detection, and therefore specific protocols must be validated for various
      collection procedures and cytokine assays. Our results suggest that combined
      patterns of cytokine dynamics rather than individual measurements might
      distinguish proinflammatory product-related effects in microbicide safety trials.
      More research is needed to establish cytokine mucosal baselines and modulation by
      genetic factors, sexual intercourse, menstrual cycle, exercise, hormones, stress
      and infections before guidelines can be established for clinical trial enrollment
      criteria, the prediction of side/adverse events and ultimately microbicide
      benefit prognostication.

PMID- 16419272
TI  - Sensitive methods to detect epithelial disruption: tests for microhemorrhage in
      cervicovaginal lavages.
AB  - The toxic effects of topical microbicides might include epithelial disruption,
      and if sufficiently severe, may cause visible bleeding. We have developed two
      sensitive methods to detect hemorrhage far below the visual detection threshold:
      an enzyme-linked immunosorbent assay for human hemoglobin and a method for
      staining and enumerating red blood cells by fluorescent microscopy. We have
      applied these methods to cervicovaginal and introital lavages, and found them to
      be sensitive and quantitative over a broad range. Comparing the new techniques
      with a standard heme-detection assay (Hemastix) we found them to be more
      sensitive, more objective, more fully quantitative, and more likely to be
      indicative of recent events. In pilot studies we found that the red blood cell
      and hemoglobin concentrations in samples taken in the luteal phase of the
      menstrual cycle are low, but still within the detection range of the new assays,
      providing a quantifiable baseline from which increases in blood from epithelial
      disruption can be detected and quantified. We propose that these new methods may
      be used for the safety assessment of microbicides by detecting and quantifying
      microhemorrhage in cervicovaginal secretions before and after exposure to
      microbicide.

PMID- 16419274
TI  - Weapons in the molecular arms race.

PMID- 16419275
TI  - When extreme negativity is a positive thing.

PMID- 16419276
TI  - Two Ps in the bacterial pod.

PMID- 16419277
TI  - The clinical epidemiology of contrast-induced nephropathy.
AB  - Recent improvements in contrast agents and radiologic imaging tools have resulted
      in an increasing number of patients undergoing contrast media (CM)-enhanced
      examinations. Although the majority of patients undergoing these diagnostic and
      therapeutic procedures experience only mild adverse events, some patient
      subpopulations are at risk for developing contrast-induced nephropathy (CIN), an
      adverse event that is associated with high morbidity and mortality. Contrast
      induced nephropathy is usually defined as an increase of > or =25% in the serum
      creatinine level relative to baseline. Pathophysiologic mechanisms underlying
      this disorder are not fully understood, but it is currently believed that
      disturbances in renal hemodynamics and a direct effect of CM on renal tubules are
      involved. In the general population, the incidence of CIN is estimated to be 1%
      to 6%. However, the risk may be as high as 50% in some patient subgroups.
      Patients with diabetes and pre-existing renal impairment are at high risk, and
      CIN incidence increases in patients with multiple comorbidities. The volume and
      osmolality of CM used also play a role in the development of CIN. Patients who
      develop CIN are more likely to die in-hospital and, for those who are discharged,
      1-year mortality rates are high. Whether this is due to CM, comorbidity, or
      concurrent comorbid events is unclear. Randomized controlled trials that measure
      non-renal clinical outcomes are necessary to determine whether interventions that
      prevent CIN can also prevent non-renal adverse events. A review of the incidence,
      pathogenesis, and clinical consequences of CIN is provided.

PMID- 16419278
TI  - Reducing the risks for contrast-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN) is one of the most serious adverse events
      associated with the use of contrast media (CM). Patients who develop this
      complication can have increased morbidity, higher rates of mortality, lengthy
      hospital stays, and poor long-term outcomes. Although CIN cannot be eliminated,
      the chances of developing this condition can be reduced by using appropriate
      prevention strategies. An important first step to reduce the chance of CIN is to
      identify risk factors associated with this condition. Patients with a previously
      elevated serum creatinine level, especially when secondary to diabetic
      nephropathy, are at great risk for developing CIN. Other patient-related risk
      factors include concurrent use of nephrotoxic medications, dehydration,
      congestive heart failure, age greater than 70 years, and probably the presence of
      diabetes mellitus even if serum creatinine is normal. Adequate hydration is
      widely accepted as an important prophylactic measure for preventing CIN, but the
      optimal hydration regimen is still debatable. The risk of CIN increases with
      greater doses of CM, as well as with the type of CM used. A high-osmolar CM poses
      a greater risk of CIN than does a low-osmolar CM and, as recent but limited data
      suggest, the use of an isoosmolar CM is less nephrotoxic than a low-osmolar CM in
      patients with renal impairment following intra-arterial procedures, although this
      finding needs to be verified in future clinical studies. Pharmacologic agents
      such as calcium channel blockers, dopamine, atrial natriuretic peptide,
      fenoldopam, prostaglandin El, and endothelin receptor antagonist have not been
      proven effective against CIN development. Controversies still exist on the
      possible effectiveness of theophylline and N-acetylcysteine. Simple strategies
      for the prevention of CIN in at-risk patients are reviewed and unproven
      interventions are discussed.

PMID- 16419279
TI  - Warning on Liqiang 4 dietary supplements.

PMID- 16419280
TI  - FDA updates labeling for erectile dysfunction drugs.

PMID- 16419281
TI  - Safe cider and juice.

PMID- 16419282
TI  - New therapy for advanced HIV.

PMID- 16419283
TI  - Update on counterfeit drugs.

PMID- 16419284
TI  - FDA asks Purdue Pharma to withdraw Palladone.

PMID- 16419285
TI  - FDA approves heart drug for black patients.
AB  - The Food and Drug Administration's approval in June 2005 of a heart failure drug
      aimed at black patients marks the first time that the agency has approved a drug
      for a specific racial group. When added to standard heart failure therapy, BiDil
      dramatically reduces death and hospitalization in blacks.

PMID- 16419286
TI  - Controlling urinary incontinence.

PMID- 16419287
TI  - Medical devices needed for children.

PMID- 16419288
TI  - Saving money on prescription drugs.

PMID- 16419289
TI  - Prevent you child from choking.

PMID- 16419290
TI  - Epilepsy and seizures can occur at any age.

PMID- 16419292
TI  - Weight loss. Strategies that work.

PMID- 16419291
TI  - Take time for a mammogram.
AB  - If you're a woman over 40 and you can't remember the last time you had a
      mammogram, you may be overdue. The National Cancer Institute (NCI) estimates that
      1 in 8 women will be diagnosed with breast cancer at some time in their lives.
      But the good news is that mammograms--X-ray pictures of the breast--can detect
      breast cancer early, when it's most treatable.

PMID- 16419293
TI  - Health tips. Lowering cholesterol with diet and drugs.

PMID- 16419294
TI  - Prostate obstruction associated with chronic kidney disease.

PMID- 16419295
TI  - Urinary incontinence. Know your drug options.

PMID- 16419296
TI  - Less stress. Ten ways to manage it day by day.

PMID- 16419297
TI  - I use baking soda as an antacid. But my wife tells me it's high in salt and I
      shouldn't use it since I'm on a salt-restricted diet. Is that true?

PMID- 16419299
TI  - New York state recommendations for drug-drug interactions between HAART,
      medications used in substance use treatment, and recreational drugs--a summary.

PMID- 16419298
TI  - Antiretroviral therapy update from the 44th ICAAC.

PMID- 16419300
TI  - 3rd IAS conference: initial therapy, switching, and new strategies.

PMID- 16419302
TI  - 3rd IAS conference: pregnancy issues.

PMID- 16419301
TI  - 3rd IAS conference: new drugs and treatment of experienced patients.

PMID- 16419303
TI  - 3rd IAS conference: prevention highlights.

PMID- 16419304
TI  - Targeting HIV reservoirs with valproic acid.

PMID- 16419305
TI  - 3rd IAS conference: metabolic and fat metabolism issues.

PMID- 16419306
TI  - Update from the 6th International Workshop on the Clinical Pharmacology of HIV
      Therapy: new drugs, new formulations and drug interactions.

PMID- 16419307
TI  - Highlights from the 2005 National HIV Prevention Conference.

PMID- 16419308
TI  - FDA approves Aptivus (tipranavir).

PMID- 16419309
TI  - Clinical implications of HIV viral load blips.

PMID- 16419311
TI  - Pharmacology at the 12th CROI: generic antiretrovirals, drug interactions, and
      therapeutic drug monitoring.

PMID- 16419310
TI  - Report from Boston: the 12th Conference on Retroviruses and Opportunistic
      Infections (CROI). Complications/toxicity of HIV therapy.

PMID- 16419312
TI  - Viral hepatitis treatment and beyond: a review of CROI 2005.

PMID- 16419313
TI  - Report from Boston: the 12th Conference on Retroviruses and Opportunistic
      Infections (CROI). Reduced bone mineral density in HIV-infected patients.

PMID- 16419314
TI  - FDA approves Pegasys and Copegus for hepatitis C in patients with HIV co
      infection.

PMID- 16419315
TI  - Treatment of experienced patients and antiretroviral resistance issues from the
      12th CROI.

PMID- 16419316
TI  - Treatment of naive patients: update from the 12th CROI.

PMID- 16419317
TI  - HIV and pregnancy at the 12 CROI.

PMID- 16419318
TI  - Report from Boston: the 12th Conference on Retroviruses and Opportunistic
      Infections (CROI). New drugs, new targets: good news on the horizon.

PMID- 16419319
TI  - Report from Boston: the 12th Conference on Retroviruses and Opportunistic
      Infections (CROI). The New York City patient: a case of progression,
      pathogenesis, and public health.

PMID- 16419320
TI  - Update from the 6th International Workshop on Adverse Drug Reactions and
      Lipodystrophy in HIV.

PMID- 16419321
TI  - The DHHS adult ART guidelines are revised.

PMID- 16419322
TI  - Measurement of protein glycation, glycated peptides, and glycation free adducts.
AB  - Protein glycation adducts, early glycation adducts, such as N(epsilon)-fructosyl
      lysine, and advanced glycation end products (AGEs) are uremic toxins. Glycation
      adducts are found in plasma and tissue proteins (glycation adduct residues), in
      peptides (glycation adduct peptide residues), and glycated amino acids (glycation
      free adducts). The latter two analyte groups arise from proteolysis of glycated
      proteins and glycation of peptides and amino acids. Quantitation of glycation
      adducts in uremia is difficult because of the presence of many different AGEs at
      low concentrations in different forms in the presence of many potential
      interferences. Application of liquid chromatography with tandem mass
      spectrometric (LC-MS/MS) detection to plasma, urine, and dialysate samples of
      uremic patients has provided a comprehensive and quantitative analysis of
      glycation adducts in uremia. Glycation free adducts accumulate markedly in the
      plasma of uremic patients and are eliminated in the peritoneal dialysate.
      Multiple glycation adducts, and also protein oxidation and nitration adducts, may
      be quantified concurrently. Glycation free adducts are the major form of
      glycation adduct eliminated in dialysate. LC-MS/MS may now be used to quantify
      concentrations, extents of protein modification, clearances, and excretion rates
      of glycation adducts in uremia.

PMID- 16419324
TI  - Trans fat free--is it really?

PMID- 16419325
TI  - Prepping microchips for infinity and beyond.

PMID- 16419326
TI  - Raman probe could aid brain surgeons.

PMID- 16419327
TI  - Real-time assay for GPCRs.

PMID- 16419328
TI  - Drugs in the water.

PMID- 16419329
TI  - Detecting prions in blood.

PMID- 16419330
TI  - Old alginates solve new problems.

PMID- 16419331
TI  - SERS in the spotlight.

PMID- 16419332
TI  - Portable device for live tissue imaging.

PMID- 16419333
TI  - MS on the bioterror front lines.

PMID- 16419334
TI  - Emission enhancement mechanisms in dual-pulse LIBS.

PMID- 16419336
TI  - [Radiotherapy departments' implementations and challenges with revised
      regulations].

PMID- 16419337
TI  - Antileishmanial and trypanocidal activity of Brazilian Cerrado plants.
AB  - The side effects and the emerging resistance to the available drugs against
      leishmaniasis and trypanosomiasis led to the urgent need for new therapeutic
      agents against these diseases. Thirty one extracts of thirteen medicinal plants
      from the Brazilian Cerrado were therefore evaluated in vitro for their
      antiprotozoal activity against promastigotes of Leishmania donovani, and
      amastigotes of Trypanosoma cruzi. Among the selected plants, Casearia sylvestris
      var. lingua was the most active against both L. donovani and T. cruzi. Fifteen
      extracts were active against promastigotes of L. donovani with concentrations
      inhibiting 50% of parasite growth (IC50) between 0.1-10 microg/ml, particularly
      those of Annona crassiflora (Annonaceae), Himatanthus obovatus (Apocynaceae),
      Guarea kunthiana (Meliaceae), Cupania vernalis (Sapindaceae), and Serjania
      lethalis (Sapindaceae). With regard to amastigotes of T. cruzi, extracts of A.
      crassiflora, Duguetia furfuracea (Annonaceae), and C. sylvestris var. lingua were
      active with IC50 values between 0.3-10 microg/ml. Bioassay fractionations of the
      more active extracts are under progress to identify the active antiparasite
      compounds.

PMID- 16419338
TI  - Acute generalized exanthematous pustulosis in pregnancy: more common than
      previously estimated.

PMID- 16419339
TI  - Let's get moving: addressing the new recommendations for physical activity in
      children and adolescents.

PMID- 16419340
TI  - Sports nutrition for young athletes.
AB  - Nutritional needs for peak athletic performance include sufficient calorie
      intake, adequate hydration, and attention to timing of meals. Student athletes
      and their advisors often are misinformed or have misconceptions about sports
      nutrition. This paper identifies nutritional needs of young athletes, reviews
      common misconceptions, and examines the nutrition knowledge of athletes and their
      sources of nutrition information. Topics covered include energy, carbohydrate,
      protein, fat and micronutrient needs, hydration requirements, timing of meals,
      and issues related to age, gender, and specific sports. Other issues addressed
      include "making weight" and ergogenic aids. Proper nutrition for young athletes
      is critical not only to their athletic success, but more importantly to their
      growth, development, and overall health. Nutritional recommendations should be
      based on the most current scientific data; we provide information about
      appropriate resources for the school nurse when advising student athletes and
      their coaches and parents.

PMID- 16419341
TI  - Boys with eating disorders.
AB  - Although commonly associated with girls and women, eating disorders do not
      discriminate. School nurses need to be aware that male students also can suffer
      from the serious health effects of anorexia nervosa, bulimia, anorexia athletica,
      and eating disorders not otherwise specified. Sports that focus on leanness and
      weight limits can add to a growing boy's risk of developing an eating disorder.
      Issues of body image and sexual development can complicate and can distort
      previously normal eating habits. Students may use powerful and dangerous drugs
      readily available via the Internet, including growth hormone, creatine,
      testosterone, and aminophylline, to build muscle and to eliminate fat,
      potentially causing serious health consequences. School nurses can partner with
      health and physical education teachers, coaches, school staff, parents, and
      students to identify and to support boys with eating disorders

PMID- 16419342
TI  - Handheld computer software for school nurses.
AB  - School nurses used computers in the 1980s, the Internet in the 1990s, and are
      embracing handheld computers in the first decade of the 21st century to improve
      their practice. The purpose of this article is to provide information about
      handheld computers and software applications that school nurses can use in day-to
      day, emergency, and disaster situations. Handheld computers help school nurses to
      make decisions based on accurate and up-to-date information, and to practice
      evidence-based nursing. Evidence-based nursing is the process by which nurses
      make clinical decisions using the best available research evidence, their
      clinical expertise, and patient preferences.

PMID- 16419343
TI  - Viva la revolution!

PMID- 16419344
TI  - The guardian angel of CPR.

PMID- 16419345
TI  - Where we fail: research reveals our weaknesses in CPR delivery.

PMID- 16419346
TI  - EMS leaders weigh in.

PMID- 16419347
TI  - Real-world findings.

PMID- 16419348
TI  - Q-CPR eliminates guesswork: measurement & feedback keep rescuers on target.

PMID- 16419349
TI  - Bystander CPR: a new video-based training program delivers the right message to
      the right people.

PMID- 16419350
TI  - Downtown people: taking care of America's homeless--& their caregivers.

PMID- 16419351
TI  - Sorting through confusion: prehospital identification & treatment of dementia &
      delirium.

PMID- 16419352
TI  - The metabolic syndrome: time for a critical appraisal: joint statement from the
      American Diabetes Association and the European Association for the Study of
      Diabetes: response to Kahn et al.

PMID- 16419353
TI  - The metabolic syndrome: time for a critical appraisal: joint statement from the
      American Diabetes Association and the European Association for the Study of
      Diabetes: response to Kahn et al.

PMID- 16419354
TI  - The metabolic syndrome: time for a critical appraisal: joint statement from the
      American Diabetes Association and the European Association for the Study of
      Diabetes: response to Kahn et al.

PMID- 16419355
TI  - The metabolic syndrome: time for a critical appraisal: joint statement from the
      American Diabetes Association and the European Association for the Study of
      Diabetes: response to Kahn et al.

PMID- 16419356
TI  - The case for biennial retinopathy screening in children and adolescents: response
      to Maguire et al.

PMID- 16419357
TI  - Of genes and men: the alternative view of sex differences in cystic fibrosis:
      response to Sims et al. and Milla et al.

PMID- 16419358
TI  - Low plasma adiponectin levels are associated with increased hepatic lipase
      activity in vivo: response to Schneider et al.

PMID- 16419359
TI  - A comment from a humane experimental technique perspective on the Nuffield
      Council on Bioethics report on The ethics of research involving animals.

PMID- 16419360
TI  - The ethics of research involving animals: a review of the Nuffield Council on
      Bioethics report from a research perspective.

PMID- 16419361
TI  - The ethics of research involving animals: a review of the Nuffield Council on
      Bioethics report from a three Rs perspective.

PMID- 16419362
TI  - The ethics of research involving animals: a review of the Nuffield Council on
      Bioethics report from an antivivisectionist perspective.

PMID- 16419363
TI  - Genomics and society: the ESRC genomics network.

PMID- 16419364
TI  - EMALT: a Brazilian Meeting on Alternative Methods to Animal Use for Regulatory
      Purposes.

PMID- 16419365
TI  - [Research in arbovirus should be strengthened in China].

PMID- 16419366
TI  - For love of the profession. Steven M. Coplon--Medical Practice Executive of the
      Year Award.

PMID- 16419367
TI  - For love of the profession. Kurt W. Tauer--Physician Executive of the Year Award.

PMID- 16419368
TI  - For love of the profession. Bedlam Community Health Partnerships--Fred Graham
      Award for Innovation in Improving Community Health.

PMID- 16419369
TI  - For love of the profession. Kenneth T. Hertz--Edward B. Stevens Article of the
      Year Award.

PMID- 16419370
TI  - "Chasing the dragon"--imaging of heroin inhalation leukoencephalopathy.
AB  - "Chasing the dragon" refers to the inhalation of heroin pyrolysate vapors
      produced when the freebase form of heroin is heated. Inhalation of these vapors
      can result in a rare toxic spongiform leukoencephalopathy. The patients may
      progress through 3 defined clinical stages, with one-quarter reaching the
      terminal stage, which invariably leads to death. Imaging and, in particular,
      magnetic resonance imaging (MRI) demonstrates white matter findings that are felt
      to be specific for this entity and essential in its early diagnosis. We present
      the typical imaging findings in a pictorial essay format, using images taken from
      9 patients who presented within an 18-month period at UBC-affiliated hospitals.
      These findings include low computed tomography (CT) attenuation and high T2 MRI
      signal most commonly in the posterior cerebral and cerebellar white matter,
      cerebellar peduncles, splenium of the corpus callosum, and posterior limb of the
      internal capsules. In addition, there is often selective, symmetric involvement
      of the corticospinal tract, the medial lemniscus, and the tractus solitarius. We
      also present the variable diffusion-weighted imaging and apparent diffusion
      coefficient findings from 4 of our patients, which to our knowledge, have not
      been described in the literature.

PMID- 16419371
TI  - Neuroimaging of language processes: fMRI of silent and overt lexical processing
      and the promise of multiple process imaging in single brain studies.
AB  - OBJECTIVE: To implement and evaluate a multiple-process functional magnetic
      resonance imaging (fMRI) paradigm designed to effectively and efficiently
      activate several language-related regions for use with neurosurgical patients.
      Both overt and covert response conditions were examined. METHODS: The fMRI
      experiments compared the traditional silent word-generation condition versus an
      overt one as they engage frontal language regions (Experiment 1) and silent
      versus overt semantic association conditions as they engage multiple language
      processing regions (Experiment 2). RESULTS: In Experiment 1, the overt condition
      yielded greater magnitude of activation, but not volume of activation, in the
      left inferior frontal and insular cortices than did the silent condition for
      most, but not all, participants. Experiment 2 demonstrated that the activation of
      multiple established language processing regions (ie, orthographic, phonological,
      and semantic) can be achieved in a significant number of participants,
      particularly under overt semantic association conditions and that such activation
      varies in predictable ways. CONCLUSION: The traditional silent response condition
      cannot be considered as equivalent to the overt response condition during word
      generation or semantic association. The multiple-process imaging method
      introduced here was sensitive to processing robust orthographic, phonological,
      and semantic regions, particularly under the overt response condition.

PMID- 16419372
TI  - Intravascular pulmonary metastases from sarcoma: appearance on computed
      tomography in 3 cases.
AB  - INTRODUCTION: Various common malignant neoplasms (ie, liver, kidney, stomach, and
      breast) have been reported to embolize to the pulmonary arterial system. This
      uncommon occurrence can also result from metastatic sarcoma. We report 3 cases--2
      chondrosarcomas and 1 osteosarcoma-associated with intravascular metastases to
      the pulmonary vasculature and discuss the clinical presentation and
      differentiating radiologic features on computed tomography (CT). DISCUSSION:
      Intravascular pulmonary tumour emboli may present with nonspecific respiratory
      symptoms or remain completely asymptomatic, and therefore, many patients are
      often misdiagnosed with thromboembolic disease or undiagnosed until autopsy.
      Chest CTs in all our patients demonstrated a striking pattern of multifocal
      tubular branching beaded opacities along the pulmonary vasculature in a
      multilobular distribution. CONCLUSION: Our observations and a review of the
      literature indicate that chest CT is the most useful diagnostic tool for
      detecting intravascular pulmonary tumour emboli. CT can distinguish this entity
      from mucous plugging by demonstrating the normal adjacent bronchus. The tubular
      nature of these metastases distinguishes them from the more common parenchymal
      metastases.

PMID- 16419373
TI  - Chest X-ray ordering related to varied clinical scenarios: a survey of
      Saskatchewan physicians.
AB  - INTRODUCTION: The chest X-ray (CXR) is one of the most commonly requested
      diagnostic imaging examinations. It is estimated that over 250,000 CXRs are
      ordered in Saskatchewan annually. Judicious use of the CXR is valuable in patient
      care, while unnecessary use increases costs, adds to patient irradiation, and may
      be in conflict with standards of patient care. In 1993, the Saskatchewan Health
      Services Utilization and Research Commission (HSURC) developed clinical practice
      guidelines (CPGs) for the CXR. These guidelines were based on a metaanalysis of
      validated literature. We were uncertain about whether Saskatchewan physicians
      were ordering CXRs based on the HSURC CXR CPGs. MATERIALS AND METHODS: A survey,
      based on recommendations from the HSURC CXR CPGs, was developed and distributed
      to 363 physicians in Saskatchewan by mail (30/363) and by email (333/363). The
      survey asked physicians if they would order, or not order, a CXR for 5 basic
      clinical scenarios. The question of whether to order a CXR was then repeated when
      the basic scenario was altered one variable at a time, to determine if the
      physicians would change their CXR orders. RESULTS: According to our assessment of
      physician responses to the initial clinical scenarios, the surveyed physicians
      correctly followed the HSURC CXR CPGs in the following frequencies: 100% scenario
      1, 91.9% scenario 2, 35.4% scenario 3, 100% scenario 4, and 61.2% scenario 5.
      Alteration of the basic clinical scenarios resulted in very unpredictable
      ordering of CXRs by the survey participants. CONCLUSION: The Saskatchewan
      physicians we surveyed are not ordering CXRs on the basis of HSURC CXR CPGs. They
      order too many nonindicated CXRs. Further communication with, and education of,
      the physician population about the HSRUC CXR CPGs may be warranted.

PMID- 16419374
TI  - Introducing Integrating the Healthcare Enterprise--Canada.

PMID- 16419375
TI  - Does gender impact upon application rejection rate among Canadian radiology
      residency applicants?
AB  - PURPOSE: To determine if and how gender ratios have changed within Canadian
      radiology, and to determine if gender discrimination occurs at the level of the
      radiology resident selection committee. METHODS: The Canadian Medical
      Association, Canadian Association of Radiologists, Canadian Institute for Health
      Information, Royal College of Physicians and Surgeons of Canada, and Canadian
      Residency Matching Service provided gender-specific data. We compared the
      proportion of female applicants who ranked a radiology program as their top
      choice and were rejected from any radiology program with the corresponding
      proportion for male applicants. RESULTS: The numbers of women and men being
      awarded an MD from a Canadian university equalized nearly a decade ago. Women
      continue to be numerically underrepresented among practicing radiologists;
      however, the proportion of women continues to increase so that there is 1 female
      radiologist in practice to every 3 male radiologists in practice in 2005. More
      male medical students ranked a radiology residency training program as their top
      choice in the residency match; however, of those who did, they were as likely as
      women to be rejected from a radiology residency training program. Grouping all
      female and male graduating medical students participating in the residency match
      and ranking a radiology residency as their top choice between 1993 and 2004, the
      odds of men being rejected were 1.4 times (95% CI 0.99-1.9, p = 0.07) greater
      than for women. CONCLUSIONS: There continues to be more men than women
      radiologists in practice; however, the female-to-male ratio continues to
      increase. Our data suggest that discrimination against female applicants at the
      level of radiology residency selection does not occur.

PMID- 16419376
TI  - Reliability and comparison of acromion assessment techniques on X-ray and
      magnetic resonance imaging (reliability of acromion assessment techniques).
AB  - OBJECTIVE: To determine the reliability and correlation of plain radiography and
      magnetic resonance imaging (MRI) in the assessment of acromion morphology.
      MATERIALS AND METHODS: Acromion morphology was assessed using the lateral
      acromion angle (LAA) and the acromion-humeral interval (AHI). Thirty patients who
      had X-rays and MRI for impingement syndrome were included. Six blinded observers
      assessed the acromion morphology subjectively and objectively. RESULTS: Neither
      acromion assessment technique demonstrated a positive correlation (kappa and
      intraclass coefficient < 0.55) between X-ray and MRI. Both techniques were
      reliable (kappa and intraclass coefficient > 0.55) when measured objectively by
      experienced observers. CONCLUSION: The LAA and the AHI are both reliable acromion
      assessment techniques on X-ray and MRI when measured objectively and by
      experienced observers.

PMID- 16419377
TI  - Answer to case of the month #103. Large subserosal uterine leiomyoma with cystic
      degeneration presenting as an abdominal mass.

PMID- 16419378
TI  - Answer to case of the month #104. Congenital arterioportal fistula with patent
      ductus venosus.

PMID- 16419379
TI  - A devilish surprise.

PMID- 16419380
TI  - From general and communal hygiene to the center of environmental health and
      center of health promotion and protection.

PMID- 16419381
TI  - Lower stroke death rates in patients receiving blood pressure lowering therapy
      before the onset of a stroke.
AB  - The objective of this study was to compare stroke death rates among patients with
      and without blood pressure lowering treatment before the onset of the stroke.
      During two consecutive years all patients with acute stroke were recorded by 178
      Belgian general practitioners of the sentinel network. In total 511 patients with
      acute stroke were recorded. The death rate after one month was found
      significantly higher among the untreated patients (33%; n = 84) compared to those
      receiving blood pressure lowering treatment (23%; n = 61) (p = 0.007). Blood
      pressure lowering treatment before the onset of stroke had a beneficial effect on
      survival in a backward stepwise logistic regression (OR 0.38; 95% CI 0.20-0.72).
      In conclusion, stroke mortality is significantly lower among patients receiving
      blood pressure lowering treatment before the onset of stroke compared to those
      without blood pressure lowering treatment.

PMID- 16419382
TI  - State of the art coronary heart disease risk estimations based on the Framingham
      heart study.
AB  - The aim was to review the most interesting articles dealing with estimations of
      an individual's absolute coronary heart disease risk based on the Framingham
      heart study. Besides the Framingham coronary heart disease risk functions,
      results of validation studies of these Framingham risk functions are discussed.
      In general, the Framingham risk functions overestimated an individual's absolute
      risk in external (non-Framingham) populations with a lower occurrence of coronary
      heart disease compared with the Framingham population, and underestimated it in
      populations with a higher occurrence of coronary heart disease. Even if the
      calibration accuracy of the Framingham risk functions were not satisfying, the
      Framingham risk functions were able to rank individuals according to risk from
      low-risk to high-risk groups, with the discrimination ability of 60% and more.

PMID- 16419383
TI  - Are there associations between socio-economic status and known diabetes in an
      elderly Finnish population?
AB  - The aim of the study was to describe the associations between socio-economic
      status and type 2 diabetes in a non-institutionalised population aged 70 years or
      over. Diabetes was assessed on the basis of self-reports and additionally 2-h
      oral glucose tolerance test for the subjects on diet treatment. Socio-economic
      status was assessed by questions on marital status, number of residents in
      household, basic education, self-rated income and economic status. In the
      population of 379 subjects (141 men), 14% (n = 19) of men and 19% (n = 46) of
      women had known diabetes. Known diabetes was less common among married compared
      to unmarried, widowed or divorced subjects. Diabetes was also more common among
      men with higher compared to lower level of basic education, while a reverse trend
      was seen among women. Women, who had been engaged in manual labour, had diabetes
      more often compared to those engaged in administrative work. Diabetes was more
      common among men who rated their income as good, but the opposite was true of
      women. Higher income among men and lower income among women were the most
      powerful variables associated with known diabetes. Known diabetes was more common
      in elderly women with lower socio-economic status, whereas the opposite was true
      of men. This finding suggests that the impact of the socio-economic changes that
      have taken place in Finland in the 20th century on the risk factors for diabetes
      has been greater among men with higher and women with lower socio-economic
      status.

PMID- 16419384
TI  - Correlations of somatophysiological, biochemical, psychosocial and behavioral
      risk factors of cardiovascular diseases in a sample of employees of Prague
      enterprises and institutions.
AB  - The study is aimed at the detection and intervention of risk factors for
      cardiovascular diseases (CVD) and at the part played by stress in their
      development. The methods applied are designed to eliminate the risks and,
      simultaneously, to identify the function of the two main parts of stress
      reaction, i.e., in terms of the extent, level and type of the stressors
      experienced, and in terms of the level of mental resilience and related
      psychosocial factors which affect the experiencing of and coping with stress. The
      purpose of medical examination based on the patient's history, subjective
      complaints and objective tests, including a study of dietary habits and
      psychological methods was to establish the status praesens and identify the main
      risk factors and symptoms leading to ischemic heart disease (IHD). Intervention
      was performed in subjects with increased cardiovalscular risk factors.

PMID- 16419385
TI  - Introducing Evidence-Based Medicine and guidelines for maternal and newborn care
      in the Republic of Moldova.
AB  - Familiarity with Evidence-Based Medicine (EBM) concepts is low amongst key
      maternal and newborn care clinicians in Moldova. Simple interventions can
      increase the knowledge of EBM concepts there.

PMID- 16419386
TI  - Effects of age, BMI, smoking and contraception on levels of Cu, Se and Zn in the
      blood of the population in the Czech Republic.
AB  - Variations in the levels of Cu, Se and Zn in blood were analyzed in relation to
      gender, age, BMI, smoking and hormonal contraception. The blood samples were
      collected from 3,207 blood donors (2,362 men, 845 women) during years 1996-2003.
      Blood concentrations of these elements were in the same range as those found for
      populations of other European countries. Significant differences exist between
      men and women, in blood concentration, for Cu (840 microg Cu.l(-1) vs. 970 microg
      Cu.l(-1), p<0.01) and Zn (6,780 microg Zn.l(-1) vs. 6,235 microg Zn.l(-1),
      p<0.01) only. The level of Cu in relation to age is increasing in men, but
      decreasing in women. The level of Se in relation to age increases regardless of
      sex. Concentrations of Zn rise with age in women group, only. Positive
      correlation was found between BMI and level of Cu only for group of men. For Se
      levels and BMI differences exist only in men namely between groups <20 and >35
      (82 microg Se.l(-1) vs. 92 microg Se.l(-1)). Slight positive correlations exist
      between Zn concentration and BMI in women only. The significant differences were
      found between smokers and non-smokers for Cu in men (850 microg Cu.l(-1) vs. 830
      microg Cu.l(-1)) and Se (81 microg Se.l(-1) vs. 84 microg Se.l(-1)). The smoking
      has not significant influence on concentration of Zn in the blood. The hormonal
      contraception significantly increases the concentration of Cu in blood (920
      microg Cu.l(-1) vs. 1,270 microg Cu.l(-1), p<0.01). The levels of Se and Zn in
      blood are not influenced using hormonal contraception.

PMID- 16419387
TI  - Pharmacogenomics as molecular autopsy for forensic toxicology: genotyping
      cytochrome P450 3A4*1B and 3A5*3 for 25 fentanyl cases.
AB  - Pharmacogenomics, the study on genetic contributions to drug action may help in
      certifying fentanyl toxicity. Fentanyl is used clinically as an adjunct to
      surgical anesthesia and for chronic pain management. Its toxicity may be
      partially due to cytochrome P450 (CYP) 3A4*1B and 3A5*3 variant alleles,
      resulting in variable fentanyl metabolism. In this study, we examined 25 fentanyl
      related deaths (22 Caucasians, 1 African-American, and 2 Native-Americans) from
      the Milwaukee County Medical Examiner's Office and referral cases. Fentanyl and
      norfentanyl in postmortem blood samples were analyzed by radioimmunoassay and
      liquid chromatography-mass spectrometry-mass spectrometry. The samples were then
      genotyped for CYP3A4*1B and 3A5*3 using Pyrosequencing. Genotyping showed: 1
      CYP3A4*1B homozygous and CYP3A5*3 heterozygous, 1 compound CYP3A4*1B and CYP3A5*3
      heterozygous, 22 CYP3A4*1B wild type and CYP3A5*3 homozygous, and 1 CYP3A5*3 and
      CYP3A4*1B wild type. CYP variant allelic frequencies of the 25 cases were 6% for
      CYP3A4*1B and 92% for CYP3A5*3, compared with normal Caucasian CYP3A4*1B, 3-8%,
      and CYP3A5*3, 85-95%. The mean fentanyl concentration and metabolic ratio of
      fentanyl to norfentanyl of the 2 cases with CYP3A4*1B and CYP3A5*3 variants were
      12.8 and 1.4 microg/L, respectively, lower than those of 22 cases with wild type
      CYP3A4*1B and CYP3A5*3 homozygous variants, 16.7 and 7.3 microg/L, respectively.
      The postmortem/in vivo data provided the first scientific evidence that CYP3A5 is
      involved in the fentanyl metabolism, and homozygous CYP3A5 *3 causes impaired
      metabolism of fentanyl, and genotyping CYP3A4*1B and 3A5*3 variants may help to
      certify the fentanyl toxicity.

PMID- 16419388
TI  - Investigation of an LC-MS-MS (QTrap) method for the rapid screening and
      identification of drugs in postmortem toxicology whole blood samples.
AB  - The QTrap liquid chromatography-tandem mass spectrometry (LC-MS-MS) by Applied
      Biosystems was investigated as an adjund to enzyme immunoassay (EIA) for the
      rapid detection of drugs in blood. Thus, a procedure used to identify drugs in
      whole blood by EIA was extended to LC-MS-MS analysis. A multiple reaction
      monitoring (MRM) database of over 100 drugs was constructed to analyze for those
      drugs commonly observed in postmortem toxicology cases. The QTrap method provided
      for a scan time of only 2.8 s to produce both an MRM and an enhanced product ion
      scan. Various validation and developmental steps of the method are presented, as
      well as a concordance study as a final means of validation. This study was
      conducted to compare the effectiveness of the QTrap versus conventional
      extraction methods and gas chromatography-MS for the identification of drugs in
      95 postmortem samples. The more than 400 drug results in this study showed 100%
      concordance between the two techniques.

PMID- 16419389
TI  - Passive cannabis smoke exposure and oral fluid testing. II. Two studies of
      extreme cannabis smoke exposure in a motor vehicle.
AB  - Two studies were conducted to determine if extreme passive exposure to cannabis
      smoke in a motor vehicle would produce positive results for delta
      tetrahydrocannabinol (THC) in oral fluid. Passive exposure to cannabis smoke in
      an unventilated room has been shown to produce a transient appearance of THC in
      oral fluid for up to 30 min. However, it is well known that such factors as room
      size and extent of smoke exposure can affect results. Questions have also been
      raised concerning the effects of tobacco when mixed with marijuana and THC
      content. We conducted two passive cannabis studies under severe passive smoke
      exposure conditions in an unventilated eight-passenger van. Four passive subjects
      sat alongside four active cannabis smokers who each smoked a single cannabis
      cigarette containing either 5.4%, 39.5 mg THC (Study 1) or 10.4%, 83.2 mg THC
      (Study 2). The cigarettes in Study 1 contained tobacco mixed with cannabis;
      cigarettes in Study 2 contained only cannabis. Oral fluid specimens were
      collected from passive and active subjects with the Intercept Oral Specimen
      Collection Device for 1 h after smoking cessation while inside the van (Study 1)
      and up to 72 h (passive) or 8 h (active) outside the van. Additionally in Study
      1, Intercept collectors were exposed to smoke in the van to assess environmental
      contamination during collection procedures. For Study 2, all oral fluid
      collections were outside the van following smoking cessation to minimize
      environmental contamination. Oral samples were analyzed with the Cannabinoids
      Intercept MICRO-PLATE EIA and quantitatively by gas chromatography-tandem mass
      spectrometry (GC-MS-MS). THC concentrations were adjusted for dilution (x 3). The
      screening and confirmation cutoff concentrations for THC in neat oral fluid were
      3 ng/mL and 1.5 ng/mL, respectively. The limits of detection (LOD) and
      quantitation (LOQ) for THC in the GC-MS-MS assay were 0.3 and 0.75 ng/mL,
      respectively. Urine specimens were collected, screened (EMIT, 50 ng/mL cutoff),
      and analyzed by GC-MS-MS for THCCOOH (LOD/LOQ = 1.0 ng/mL). Peak oral fluid THC
      concentrations in passive subjects recorded at the end of cannabis smoke exposure
      were up to 7.5 ng/mL (Study 1) and 1.2 ng/mL (Study 2). Thereafter, THC
      concentrations quickly declined to negative levels within 30-45 min in Study 1.
      It was found that environmentally exposed Collectors contained 3-14 ng/mL in
      Study 1. When potential contamination during collection was eliminated in Study
      2, all passive subjects were negative at screening/confirmation cutoff
      concentrations throughout the study. Oral fluid specimens from active smokers had
      peak concentrations of THC approximately 100-fold greater than passive subjects
      in both studies. Positive oral fluid results were observed for active smokers 0-8
      h. Urine analysis confirmed oral fluid results. These studies clarify earlier
      findings on the effects of passive cannabis smoke on oral fluid results. Oral
      fluid specimens collected in the presence of cannabis smoke appear to have been
      contaminated, thereby falsely elevating THC concentrations in oral fluid. The
      risk of a positive test for THC was virtually eliminated when specimens were
      collected in the absence of THC smoke.

PMID- 16419391
TI  - Urine pH, container composition, and exposure time influence adsorptive loss of
      11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid.
AB  - 11-nor-delta9-Tetrahydrocannabinol-9-carboxylic acid (11-nor-delta9-THC-COOH) is
      the primary cannabinoid present in the urine of individuals who have used
      marijuana and is the target analyte identified at forensic urinalysis drug
      testing laboratories. The preparation, storage, transport, and processing of
      control materials for gas chromatography-mass spectrometric (GC-MS) analysis of
      human urine specimens is critical to accurate compound identification and
      quantification. Previous studies have suggested that adsorptive loss of 11-nor
      delta9-THC-COOH is influenced by container composition and storage temperature.
      In this study, urine solutions of 11-nor-delta9-THC-COOH (7.5, 15, 60, and 500
      ng/mL) at three physiologically-relevant pHs (4.6, 6.5, and 8.4) were prepared
      and subjected to storage and processing in containers of different compositions
      (polypropylene and borosilicate glass). Analyte identification and quantification
      were achieved using tetramethylammonium hydroxide/iodomethane-based
      derivatization followed by GC separation and electron-impact MS. These analyses
      demonstrate that adsorptive loss of 11-nor-delta9-THC-COOH is a phenomenon found
      in acidic urine solutions and is relatively absent in urine solutions that are
      near-neutral or basic. Furthermore, the data indicate that the adsorptive loss of
      11-nor-delta9-THC-COOH is dependent on solution-container exposure time and is
      similar between containers of two distinct compositions. These results suggest
      that for optimal analytical control performance, solution pH and control
      processing times are critical elements.

PMID- 16419390
TI  - Validation of a liquid chromatography-tandem mass spectrometry method for the
      simultaneous determination of 26 benzodiazepines and metabolites, zolpidem and
      zopiclone, in blood, urine, and hair.
AB  - A liquid chromatography-tandem mass spectrometry method was developed for the
      simultaneous quantification of 26 benzodiazepines and metabolites, zolpidem and
      zopiclone, in blood, urine, and hair. Drugs were extracted from all matrices by
      liquid-liquid extraction with 1-chlorobutane. Chromatography was achieved using a
      XTerra MS C18 column eluted with a mixture of methanol and formate buffer. Data
      were acquired using positive electrospray ionization and multiple reaction
      monitoring using one precursor ion/product ion transition per compound.
      Quantification was performed using 13 deuterated analogues. Further confirmation
      of the identity of the compounds was achieved through a second injection of
      positive samples, monitoring two transitions per compound. The limits of
      quantification for all benzodiazepines ranged from 1 to 2 ng/mL in blood, 10 to
      25 ng/mL in urine, and 0.5 to 10 pg/mg in hair. Linearity was observed from the
      limit of quantification of each compound to 200 ng/mL, 1000 ng/mL, and 1000 pg/mg
      for blood, urine, and hair, respectively (r2 > 0.99). Precision for quality
      control samples, spiked at three concentrations, was calculated (CV < 20% in most
      cases). Extraction recoveries for the three matrices ranged from 25.1 to 103.8%,
      except for one compound (cloxazolam in urine). Ion suppression was studied for
      all matrices. The validated assay was applied to authentic blood, urine, and hair
      samples from forensic cases.

PMID- 16419392
TI  - Usefulness of roadside urine drug screening in drivers suspected of driving under
      the influence of drugs (DUID).
AB  - In Belgium, the driving under the influence of drugs (DUID) procedure consists of
      three steps: observation of external signs of drug consumption by a police
      officer; an on-site urine test for amphetamines, cannabinoids, cocaine, and
      opiates; and blood sampling by a physician for gas chromatography-mass
      spectrometry analysis. The driver is sanctioned if THC is greater than 2 ng/mL,
      morphine is greater than 20 ng/mL, or amphetamine, methylenedioxymethamphetamine
      (MDMA), methylenedioxyethylamphetamine, N-methyl-1-(3.4-methylenedioxyphenyl)-2
      butanamine, cocaine, or benzoylecgonine are greater than 50 ng/mL in plasma. We
      analyzed the results of 450 blood samples taken from May 2000 to February 2005.
      Cannabis was most often found above the cut-off (73.5% of the cases), followed by
      MDMA (20.4%), amphetamine (19.8%), benzoylecgonine (17.9%), cocaine (6.9%), and
      morphine (2.7%). One drug was found in 72.0% of the cases, two drugs in 22.6%,
      three drugs in 5.2%, and four drugs in 0.25%. In 10.7% of the plasma samples no
      target drugs were found above the legal cut-off. This percentage was 8.4% when
      urine was obtained and tested on-site and 21.2% when no urine was obtained (chi2
      = 8.574, P = 0.0034). In 64.6% of these samples, a target drug (THC in 74.2%) was
      found under the legal cut-off. These data indicate that roadside urine testing
      significantly decreases the number of unnecessary blood analyses in DUID.

PMID- 16419393
TI  - The identification of mivacurium and metabolites in biological samples.
AB  - Mivacurium is a muscle relaxant that is used in hospitals and has been implicated
      in a number of homicides. A validated, sensitive method for the analysis of
      mivacurium and metabolites from biological specimens is presented here. Sample
      cleanup involves the precipitation of proteins with acetonitrile followed by
      analyte isolation using a commercially available solid-phase extraction column.
      Screening is performed by liquid chromatography with fluorescence detection, and
      confirmation is performed by liquid chromatography with tandem mass spectrometric
      detection. This method has been used to analyze dozens of forensic samples,
      including clinical specimens from living patients, as well as autopsy specimens
      from exhumed bodies.

PMID- 16419395
TI  - Quantitative and isomeric determination of amphetamine and methamphetamine from
      urine using a nonprotic elution solvent and R(-)-alpha-methoxy-alpha
      trifluoromethylphenylacetic acid chloride derivatization.
AB  - Forensic Urine Drug Testing Laboratories often requires two confirmatory methods
      for a methamphetamine positive screen. First, methamphetamine is identified and
      quantitated using gas chromatography-mass spectrometry. If the total
      methamphetamine concentration is above the administrative cutoff level, the
      isomeric composition must be determined. This eliminates a possible contribution
      by over-the-counter cold medications that contain l-methamphetamine (Vick's
      inhalers). Products that contain only the l-isomer of methamphetamine must be
      distinguishable from prescription or illicitly manufactured methamphetamine,
      which consists mainly of the d-isomer. Optically impure derivatizing reagents
      will produce an impure mixture from a pure isomeric compound. Therefore, methods
      utilizing impure reagents can prove problematic when interpreting results. Use of
      an optically pure chiral derivatizing reagent, such as R(-)-alpha-methoxy-alpha
      trifluoromethylphenylacetic acid chloride, allows for the creation and
      measurement of chromatographically separable isomeric compounds. The novel method
      described here utilizes a polymer-based solid-phase column adapted to a positive
      pressure manifold extraction system and a one-step derivatization process that
      occurs directly in the elution solvent. This methodology eliminates an elution
      solvent dry-down step that may adversely affect recovery of volatile amphetamine
      compounds. Although the method was designed for the quantitative analysis of the
      isomers of amphetamine and methamphetamine, it can be adapted for use with a wide
      range of phenethylamines including methylenedioxyamphetamine, N
      methylenedioxymethamphetamine, and possibly N-methylenedioxyethylamphetamine. The
      linear range for quantitation was 25-10,000 ng/mL for d,l-methamphetamine and d,l
      amphetamine, and correlation coefficients were 0.997 or better. The coefficient
      of variation for all four analytes did not exceed 2.8%. Concentrations analyzed
      ranged from 500 to 4000 ng/mL (n=40). The method allows for a simple and accurate
      quantitation and isomeric determination of amphetamine and methamphetamine using
      a process that eliminates extraction and derivatization complications common in
      current methods.

PMID- 16419394
TI  - Investigation of fatalities due to acute gasoline poisoning.
AB  - This paper presents a simple, rapid, reliable, and validated method suited for
      forensic examination of gasoline in biological samples. The proposed methodology
      has been applied to the investigation of four fatal cases due to gasoline
      poisoning that occurred in Spain in 2003 and 2004. Case histories and
      pathological and toxicological findings are described in order to illustrate the
      danger of gasoline exposure under several circumstances. Gasoline's tissular
      distribution, its quantitative toxicological significance, and the possible
      mechanisms leading to death are also discussed. The toxicological screening and
      quantitation of gasoline was performed by means of gas chromatography (GC) with
      flame-ionization detection, and confirmation was performed using GC-mass
      spectrometry in total ion chromatogram mode. m,p-Xylene peak was selected to
      estimate gasoline in all biological samples. Gasoline analytical methodology was
      validated at five concentration levels from 1 to 100 mg/L. The method provided
      extraction recoveries between 77.6% and 98.3%. The limit of detection was 0.3
      mg/L, and the limit of quantitation was 1.0 mg/L. The linearity of the blood
      calibration curves was excellent with r2 values of > 0.997. Intraday and interday
      precisions had a coefficient of variation < or = 5.4% in all cases. Cases 1 and 2
      consist of the accidental inhalation of gasoline vapor inside a small enclosed
      space. Case 3 is a death by recreational gasoline inhalation in a male
      adolescent. Heart blood concentrations were 28.4, 18.0, and 38.3 mg/L,
      respectively; liver concentrations were 41.4, 52.9, and 124.2 mg/kg,
      respectively; and lung concentrations were 5.6, 8.4, and 39.3 mg/kg,
      respectively. Case 4 was an accidental death due to gasoline ingestion of a woman
      with senile dementia. Peripheral blood concentration was 122.4 mg/L, the highest
      in our experience. Because pathological findings were consistent with other
      reports of gasoline intoxication and constituents of gasoline were found in the
      body, cause of death was attributed to acute gasoline intoxication. As a rule,
      this kind of poisoning offers little difficulty in diagnosis because there is a
      history of exposure, and the odor usually clings to the clothes, skin, or gastric
      contents. However, anatomic autopsy findings will be nonspecific and therefore
      toxicological analysis is necessary. There is a paucity of recent references
      regarding analytical and toxicological data, and this article provides evidence
      about toxic concentrations and is a useful adjunct to the postmortem
      toxicological interpretation of fatalities if the decedent has been involved in
      gasoline use.

PMID- 16419396
TI  - Spectrophotometric detection of iodide and chromic (III) in urine after oxidation
      to iodine and chromate (VI).
AB  - Tests for oxidizing adulterants in urine are a continuing challenge to the drug
      testing program. Iodine was found to destroy morphine and 6-acetylmorphine almost
      immediately. The effects were less evident on 11 -nor-delta9-tetrahydrocannabinol
      9-carboxylic acid (THC-acid). When the urine solution was tested for iodine by a
      chromogenic substrate, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)
      (ABTS), no iodine was detected. Masking drug and adulterant simultaneously made
      iodine a preferred oxidizing adulterant for drug abusers. In this study, the
      reduced iodide was oxidized by sodium nitrite to iodine. The excess nitrite was
      decomposed by sulfamic acid and the iodine was detected by ABTS. Linearity was
      12.7 to 635 mg/L (0.1 to 5 mmol/L, y = 0.9966x + 0.0016, R2 = 1.0000). Precisions
      (coefficient of variation) were within +/- 4.1% and quantitative accuracies were
      within 97% of expected values (n=5). Chromate, iodate, periodate, and persulfate
      interfered with the method. To alleviate the problem, the positive specimens were
      tested again by an iodine-specific method. After oxidation, the samples were
      treated with sodium azide and ammonium thiocyanate. In presence of thiocyanate,
      the azide reduced iodine to iodide almost immediately, and the solutions showed
      negative response to ABTS. The results were compared with that of a control group
      tested without thiocyanate. When iodine was present, the ratios of thiocyanate to
      control were less than 6%. Chromate was also found to destroy THC-acid in urine,
      and during storage most of the chromate changed to chromic (III). In this study,
      chromic was oxidized to chromate by hydrogen peroxide and sodium hydroxide and
      detected by 1,5-diphenylcarbazide. Linearity was 5.2 to 156 mg/L (0.1 to 3.0
      mmol/L, y = 1.0285x - 0.0034, R2 = 0.9998). Precisions were within +/- 8.5% and
      quantitative accuracies were within 92% of expected values (n=5). The test was
      not interfered by other oxidizing agents. Both iodide and chromic oxidation
      methods showed urine backgrounds less than 1.27 and 0.52 mg/L, respectively (<
      0.01 mmol/L). It indicated that a response more than 10 times of the background
      could be considered as oxidant contamination or adulteration of urine specimens.

PMID- 16419398
TI  - Rapid simultaneous determination of amphetamine, methamphetamine, 3,4
      methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and 3,4
      methylenedioxyethylamphetamine in urine by fast gas chromatography-mass
      spectrometry.
AB  - The use of fast gas chromatography-mass spectrometry (FGC-MS) was investigated to
      improve the efficiency of analysis of urine specimens that previously screened
      presumptively positive for amphetamine (AMP), methamphetamine (MAMP), 3,4
      methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and/or
      3,4 methylenedioxyethylamphetamine (MDEA) by immunoassay testing. Specimens were
      pretreated with basic sodium periodate, extracted using a positive-pressure
      manifold/cation-exchange solid-phase cartridge methodology, and derivatized using
      4-carbethoxyhexafluorobutyryl chloride (4-CB). The analytical method was compared
      to traditional GC-MS analysis and evaluated with respect to assay chromatography,
      linearity, sensitivity, precision, accuracy, and reproducibility. The limits of
      detection were 62.5 ng/mL for MDA and 31.25 ng/mL for AMP, MAMP, MDMA, and MDEA.
      All of the target analytes were linear to 12,000 ng/mL with the exception of MAMP
      which was linear to 10,000 ng/mL. The intra-assay precision of a 500 ng/mL
      multiconstituent control (n=15) ranged from 522.6 to 575.9 ng/mL with a
      coefficient of variation of less than 3.8%. Authentic human urine specimens
      (n=187) previously determined to contain the target analytes were re-extracted
      and analyzed by both FGC-MS and the currently utilized GC-MS method. No
      significant differences in specimen concentration were observed between these
      analytical methods. No interferences were seen when the performance of the FGC-MS
      method was challenged with ephedrine, pseudoephedrine, phenylpropanolamine, and
      phentermine. When compared to traditional GC-MS analysis, FGC-MS analysis
      provided a dramatic reduction in retention time for amphetamine (1.8 min vs. 4.12
      min). For example, the FGC-MS method reduced overall run time for a batch of 56
      specimens from 12.0 h to 7.25 h. This reduction in analysis time makes FGC-MS an
      attractive alternative to traditional GC-MS by allowing a laboratory greater
      flexibility in the purchase and use of capital equipment and in the assignment of
      laboratory personnel, all resulting in greater overall efficiency by decreasing
      reporting times for AMP, MAMP, and designer amphetamine positive specimens.

PMID- 16419397
TI  - Rapid quantification of urinary 11-nor-delta9-tetrahydrocannabinol-9-carboxylic
      acid using fast gas chromatography-mass spectrometry.
AB  - Human urine specimens that were determined to be presumptively positive for
      metabolites of delta9-tetrahydrocannabinol by immunoassay screening were assayed
      using a novel fast gas chromatography-mass spectrometry (FGC-MS) analytical
      method to determine whether this method would improve the efficiency of specimen
      processing without diminishing the reliability of metabolite identification and
      quantification. Urine specimens were spiked with deuterated internal standard,
      subjected to solid-phase extraction, and derivatized using tetramethylammonium
      hydroxide and iodomethane. The methyl ester/methyl ether derivatives were
      identified and quantified using both a traditional GC-MS method and the newly
      developed FGC-MS method. The FGC-MS method was demonstrated to be linear between
      3.8 and 1500 ng/mL 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (11-nor
      delta-THC-COOH). The intrarun precision of 15 replicates of a 15 ng/mL control
      and the interrun precision of 161 sets of 7, 15, and 60 ng/mL controls were
      acceptable (coefficients of variation < 5.5%). The FGC-MS method was demonstrated
      to be specific for identifying 11-nor-delta9-THC-COOH and none of 43 tested
      substances interfered with identification and quantification of 11-nor-delta9-THC
      COOH. Excellent data concordance (R2 > 0.993) was found for two specimen sets
      assayed using both methods. The FGC-MS method, when compared with a traditional
      GC-MS method, reduces total assay time by approximately 40% with no decrease in
      data quality.

PMID- 16419399
TI  - Evaluation of the DRI oxycodone immunoassay for the detection of oxycodone in
      urine.
AB  - We evaluated the performance of the DRI Oxycodone (DRI-Oxy) enzyme immunoassay
      for the detection of oxycodone and its primary metabolite, oxymorphone, in urine,
      by testing 1523 consecutive urine specimens collected from pain management
      patients. All 1523 specimens were tested with the DRI-Oxy assay at a cut-off of
      100 ng/mL and then analyzed by gas chromatography-mass spectrometry (GC-MS) for
      opiates, including oxycodone and oxymorphone. Approximately 29% (435) of the 1523
      specimens yielded positive results by the DRI-Oxy assay. Of these 435 specimens,
      GC-MS confirmed the presence of oxycodone and/or oxymorphone at >100 ng/mL in 433
      specimens, an agreement of 99.5%. In addition to oxycodone and/or oxymorphone,
      189 of the 433 positive specimens contained other opiates including codeine,
      hydrocodone, hydromorphone, and morphine. These other opiates were also present
      in 54% (590/1084) of the oxycodone negative specimens. The DRI-Oxy assay
      demonstrated no cross-reactivity, yielding negative results, with specimens
      containing concentrations of codeine, >75,000 ng/mL; hydrocodone, >75,000 ng/mL;
      hydromorphone, >12,000 ng/mL; and morphine, >163,000 ng/mL. From the presented
      study, the sensitivity of the DRI-Oxy was 0.991 and the selectivity 0.998. The
      DRI-Oxy assay provided a highly reliable method for the detection of oxycodone
      and/or oxymorphone in urine specimens.

PMID- 16419401
TI  - Quantitation of R-(-)- and S-(+)-amphetamine in hair and blood by gas
      chromatography-mass spectrometry: an application to compliance monitoring in
      adult-attention deficit hyperactivity disorder treatment.
AB  - Amphetamine has been used in Attention Deficit Hyperactivity Disorder (ADHD),
      narcolepsy, and as an appetite suppressant either as the racemate or in different
      proportions of its enantiomers. In Linkoping, Sweden, the Department for Drug
      Dependence has successfully treated drug abusers also diagnosed with Adult ADHD
      with Metamina [S-(+)-amphetamine]. Because of the high risk of relapse into drug
      abuse, a strategy involving the analysis of amphetamine enantiomers in blood and
      hair was investigated for the assessment of compliance as well as abstinence from
      street amphetamine. Four patients were included: one patient was treated with
      racemic amphetamine, and three with Metamina. Blood and hair samples were
      obtained as a part of the treatment. A basic extraction of the analytes into iso
      octane was used. Hair was dissolved in sodium hydroxide before extraction. Chiral
      derivatization was performed by reaction with S-(-)-N-(trifluoroacetyl)prolyl
      chloride. Quantitation of R-(-)- and S-(+)-amphetamine was performed by gas
      chromatography-mass spectrometry in selected ion monitoring. Both blood and hair
      sample results showed good compliance for patients 1 and 2. Patient 3 and 4
      showed different percentages of S-(+)-amphetamine in hair together with varying
      total concentrations, suggesting intake of additional racemic illicit
      amphetamine. During treatment, these patients also showed other signs of
      noncompliance, and one was temporarily withdrawn from treatment. We conclude that
      the method is suitable to detect therapeutic concentrations of R-(-)- and S-(+)
      amphetamine in both blood and hair and that hair reveals noncompliance not shown
      by concentrations or enantiomer ratios in blood.

PMID- 16419400
TI  - Comparison of Cozart microplate ELISA and GC-MS detection of methadone and
      metabolites in human hair.
AB  - The purpose of this study was to determine the performance characteristics of the
      Cozart Methadone Microplate ELISA assay for the detection of methadone and
      methadone metabolites in hair specimens. One hundred and ten hair specimens were
      collected from volunteers (n=46) with a history of drug use and from drug-related
      deaths (n=64). The hair samples (approximately 20 mg) were extracted by
      sonication in methanol followed by overnight extraction in methanol at 60 degrees
      C. The methanol extract was evaporated to dryness, reconstituted in ELISA
      negative calibrator, and then analyzed. For gas chromatography-mass spectrometry
      (GC-MS) analysis, deuterated internal standard mixture [methadone-d9 and 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)-d3] and 0.1M HCI were
      added to approximately 20 mg of specimen or spiked blank hair and sonicated for 1
      h. The pH was adjusted to neutral, and methadone and its primary metabolite,
      EDDP, were analyzed by GC-MS following solid-phase extraction using Bond Elute
      Certify columns and pH 7.4 phosphate buffer (0.1M). Forty hair specimens were
      confirmed positive for methadone by GC-MS. Concentrations ranged from 0.10 to 8.3
      ng/mg for methadone and 0.1 to 1.2 ng/mg for EDDP. The true positives, true
      negatives, false positives, and false negatives for different cutoffs with the
      ELISA were determined by comparison of the ELISA response (normalized to weight
      of hair extracted) to the GC-MS results with a cutoff of 0.1 ng/mg for both
      methadone and EDDP as the reference method. The optimum cutoff for the Cozart
      Methadone Microplate ELISA was determined to be between 200 and 300 pg methadone
      equivalents/mg hair using a 20 mg hair sample. The Cozart Methadone Microplate
      EIA for methadone and metabolites in hair using a cut-off of 200 pg/mg hair with
      a 20 mg hair sample had a sensitivity of 95 +/- 2% and a specificity of 100 +/-
      3.5% (vs GC-MS) and an accuracy of 98.2 +/- 1.3%.

PMID- 16419402
TI  - Usefulness of salivary trans-3'-hydroxycotinine concentration and trans-3'
      hydroxycotinine/cotinine ratio as biomarkers of cigarette smoke in pregnant
      women.
AB  - Nicotine is rapidly and extensively metabolized in humans and negatively impacts
      the developing fetus. The concentrations of nicotine, cotinine, trans-3'
      hydroxycotinine (hydroxycotinine), and norcotinine in pregnant smokers' oral
      fluid were evaluated to determine usefulness as biomarkers of cigarette smoking.
      Sixteen participants were divided into two groups: eight light smokers (LS) who
      smoked < or =10 cigarettes/day and eight heavy smokers (HS) who smoked > or =20
      cigarettes/day. Oral fluid specimens (n=415) were collected throughout pregnancy
      and analyzed with solid-phase extraction followed by gas chromatography-mass
      spectrometry-electron impact selected ion monitoring. Median concentrations of
      nicotine, cotinine, and hydroxycotinine in oral fluid of LS ranged from 241.1 to
      622.0, 80.6 to 387.5, and 14.4 to 117.7 ng/mL and for HS 146.5-1372.2, 66.0
      245.8, and 38.3-184.4 ng/mL, respectively. Salivary cotinine and hydroxycotinine
      concentrations were significantly correlated in LS (r = 0.55, p < 0.01) and HS (r
      = 0.74, p < 0.01). Ratios of hydroxycotinine/cotinine in oral fluid from pregnant
      women averaged 0.30 +/- 0.18 (range, 0.07-1.05) for LS and 0.68 +/- 0.25 (range,
      0.29-1.83) for HS. Based on these preliminary data, the best ratio to
      differentiate light from heavy pregnant smokers was 0.41. Salivary
      hydroxycotinine and cotinine concentrations are both good biomarkers of cigarette
      smoking. Determining the hydroxycotinine/cotinine ratio may differentiate light
      from heavy tobacco use and help predict increased fetal tobacco exposure.

PMID- 16419403
TI  - Multiple aspects of hair analysis for opiates: methodology, clinical and
      workplace populations, codeine, and poppy seed ingestion.
AB  - Levels of morphine, 6-monoacetylmorphine (MAM) and codeine in hair in both
      clinical and workplace subjects are presented. Aggressive wash procedures,
      consisting of 1 isopropanol wash, three 30-min, and two 1-h buffer washes,
      followed by digestion, extraction and confirmation of digested samples, resulted
      in values from the cutoff of 2 ng morphine/10 mg hair to greater than 200 ng/10
      mg hair. Both morphine and MAM were present above the cutoff in all hair samples
      from 69 clinical subjects. Only 39 of the 69 heroin-using subjects had urine
      tests positive for 6-MAM. In a study of morphine in hair following poppy seed
      consumption, ten subjects ingested 150 g of poppy seed over 3 weeks. Urine
      samples were collected on the days of poppy seed ingestion and hair samples were
      taken in the 5th week of the study. The range among the 10 subjects of the
      highest urine value for each subject was 2929 to 13,827 ng morphine/mL. Hair
      morphine levels were 0.05-0.48 ng/10 mg hair (average 0.17 ng/10 mg hair). Hair
      opiate levels of workplace subjects ranged somewhat lower than those of clinical
      subjects. While all clinical hair samples contained MAM, many workplace samples
      did not. From workplace samples, a maximum amount of morphine likely to be
      present from codeine use was 0-3.7% of the codeine in the hair.

PMID- 16419404
TI  - Direct analysis of opiates in urine by liquid chromatography-tandem mass
      spectrometry.
AB  - A method for the direct analysis of 10 opiate compounds in urine was developed
      using liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) with
      electrospray ionization interface (ESI). Opiates included were morphine-3-P
      glucuronide, morphine-6--glucuronide, morphine, oxymorphone, hydromorphone,
      norcodeine, codeine, oxycodone, 6-monoacetylmorphine (6MAM), and hydrocodone.
      Urine samples were prepared by centrifugation to remove large particles and
      direct injection into the LC-MS-MS. Separation and detection of all compounds was
      accomplished within 6 min. Linearity was established for all opiates except 6MAM
      from 50 ng/mL to 10,000 ng/mL; 6MAM from 0.25 ng/mL to 50 ng/mL with all
      correlation coefficients (r) > 0.99. Interrun precision (%CV) ranged from 1.1% to
      16.7%, and intrarun precision ranged from 1.3% to 16.3%. Accuracy (% bias) ranged
      from -7.3% to 13.6% and -8.5% to 11.8 for inter- and intrarun, respectively.
      Eighty-nine urine samples previously analyzed by gas chromatography-MS were re
      analyzed by the LC-MS-MS method. The qualitative results found an 88% agreement
      for negative samples between the two methods and 94% for positive samples. The LC
      MS-MS method identified 19 samples with additional opiates in the positive
      samples. Overall, the direct injection LC-MS-MS method performed well and
      permitted the rapid analysis of urine samples for several opiates simultaneously
      without extensive sample preparation.

PMID- 16419405
TI  - A rapid HPLC procedure for analysis of analgesic pharmaceutical mixtures for
      quality assurance and drug diversion testing.
AB  - A simple high-performance liquid chromatographic (HPLC) method that allows for
      the rapid identification and quantification of analgesic and anesthetic solutions
      typically used in surgical procedures or patient controlled analgesia is
      presented. The separation of bupivacaine, clonidine, fentanyl, hydromorphone,
      midazolam, and morphine is complete in less than 20 min. The method allows test
      solutions to be either directly injected or diluted prior to injection into the
      HPLC system. The method is useful from the standpoint that pharmaceutical
      preparations are usually submitted with the known drug of interest and expected
      concentration. The method is also useful for initial screening of solutions
      submitted that are either unknown or of questionable identity. The method has
      been successfully applied as part of hospital-based quality control and quality
      assurance programs to detect not only errors in the preparation of solutions of
      scheduled drugs, but also to uncover illegal diversion of drugs of abuse by
      medical personnel.

PMID- 16419406
TI  - Methylation of 3,4-methylenedioxymethamphetamine in formalin-fixed human liver
      tissue.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a commonly consumed
      recreational drug. As is the case with most secondary amines, MDMA reacts with
      formaldehyde under acidic conditions to form tertiary amines. This reaction is
      likely to occur in formalin-fixed tissue. In formalin solutions, MDMA is
      methylated producing 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDA). MDDA
      standard was synthesized by treating methylenedioxyamphetamine HCl in
      formaldehyde solution. Structure confirmation was by electrospray ionization-mass
      spectrometry (MS) and MS-MS. Randomly chosen human liver pieces (100-200 mg) were
      injected with 2 microg of MDMA HCl. The liver pieces in centrifuge tubes were
      covered with 200 microL of formalin solution (20% v/v), held at room temperature
      for 24 h, and then homogenized. The resulting suspension was sonicated for 5 min
      and then centrifuged. Controls consisted of substitution of 200 microL of water
      in place of formalin solution. Supernatant aliquots (10 mciroL) were added to 500
      microL of 0.1% formic acid in acetonitrile for MS analysis. Positive ion
      electrospray spectra recorded in MS, MS2, and MS3 modes were used to confirm the
      presence of methylated MDMA. Liver tissue containing added MDMA HCl but not
      treated with formalin did not show a detectable level of methylated MDMA.

PMID- 16419407
TI  - Performance characteristics of 7-aminoflunitrazepam specific enzyme-linked
      immunosorbent assays.
AB  - With 7-aminoflunitrazepam (7-amino-FM2)-specific ELISAs now readily available
      from several commercial sources (e.g., Cozart Bioscience, Immunalysis, this study
      was conducted to evaluate the performance characteristics of these products when
      applied to the two-step testing protocol as commonly practiced in today's
      workplace drug-testing programs. Cross-reacting characteristics of these two
      assays toward a list of 25 benzodiazepines were evaluated. These assays were then
      applied to the analysis of urine specimens collected from patients treated with
      flunitrazepam (FM2) and/or other benzodiazepines. Resulting data were evaluated
      against gas chromatography-mass spectrometry (GC-MS) test data to ascertain
      corresponding cutoffs suitable for the two-step immunoassay/GC-MS testing
      strategy. Both Cozart and Immunalysis ELISAs are highly specific to 7-amino-FM2,
      with the latter reagent generating slightly higher responses. Diazepam and FM2
      (parent compound) are the only compounds with significant cross-reacting
      characteristics. With the ELISA reagents' optimal dynamic ranges set between 0
      and 25 ng/mL, urine specimens should be diluted by a factor of 5 prior to ELISA
      testing. If 30 ng/mL 7-amino-FM2 is adapted as the GC-MS cutoff, the
      corresponding ELISA cutoffs range is approximately 100-200 (or 20-40 when diluted
      by a factor of 5) ng/mL. Reagent lot and specimen characteristics (with or
      without the presence of cross-reacting compounds) affect the correlation of data
      derived from ELISA and GC-MS tests.

PMID- 16419408
TI  - Detection of cannabis use in drivers with the drugwipe device and by GC-MS after
      Intercept device collection.
AB  - Saliva or "oral fluid" has been presented as an alternative matrix in the
      establishment of drug exposure. The noninvasive collection of a saliva sample,
      which is relatively easy to perform and can be achieved under close supervision,
      is one of the most important benefits in a driving under the influence situation.
      Moreover, the presence of delta9-tetrahydrocannabinol (THC) in oral fluid is a
      better indication of recent use than when the drug is detected in urine, so there
      is a higher probability that the subject is experiencing pharmacological effects
      at the time of sampling. At 3 check points organized by the Swiss police in Bern,
      61 drivers were tested for the presence of drugs of abuse using the Drugwipe 5
      device. In parallel, oral fluid was collected with the Intercept DOA Oral
      Specimen Collection device and tested by gas chromatography-mass spectrometry (GC
      MS) after methylation of THC (limit of quantitation 1 ng/mL). The Drugwipe device
      identified 1 exposed driver, but with GC-MS, 18 drivers tested positive. THC
      concentrations in the Intercept buffer ranged from 2.1 to 205.1 ng/mL. These
      concentrations represent about 1/2 to 1/3 the authentic THC concentrations in
      oral fluid because of the dilution by the blue liquid of the device. Two main
      limitations of oral fluid were 1. the amount of matrix collected is smaller when
      compared to urine and 2. the levels of drugs in urine are higher than in oral
      fluid. A current limitation of the use of this specimen for roadside testing is
      the absence of a suitable immunoassay that detects the parent compound in
      sufficiently low concentrations.

PMID- 16419409
TI  - Simple liquid chromatographic method for the rapid and simultaneous determination
      of propoxur and its major metabolite isopropoxy phenol in rat blood and urine
      using solid-phase extraction.
AB  - This research paper describes the development and validation of an analytical
      method for the simultaneous determination of propoxur and isopropoxy phenol (IPP,
      a major metabolite) in both blood and urine of rat using reversed-phase high
      performance liquid chromatography (HPLC) employing solid-phase extraction (SPE).
      Sample purification was performed using a weak cation-exchange cartridge (Isolute
      CBA). Separation was achieved by HPLC with UV detection at 270 nm. Recoveries of
      propoxur and IPP from blood and urine by SPE exceeded 85%. The validated
      calibration range for propoxur is from 0.5 to 100 microg/L and 2 to 100 microg/L
      for IPP in both rat blood and urine. The limit of quantitation for propoxur in
      blood and urine is 0.5 and 0.8 pg/L, respectively, and 2.0 and 4.2 microg/L,
      respectively, for IPP. Validation results on specificity, sensitivity, linearity,
      precision, accuracy, and stability are shown. The applicability of the method was
      demonstrated by the analysis of urine and blood from rats that were orally fed
      propoxur at minimum dose.

PMID- 16419410
TI  - Percutaneous absorption and distribution of methanol in a homicide.
AB  - A woman was alleged to have committed suicide by consuming a gasoline additive
      shortly before jumping from a second floor balcony within her home. She was found
      dead by police with a multitude of injuries, lying nude in a partially evaporated
      unknown residue that was later determined to be methanol. Samples collected at
      autopsy were found to contain methanol in the following concentrations: femoral
      blood 31.2 mg/dL, pulmonary artery blood 111.0 mg/dL, aortic blood 77.8 mg/dL,
      vitreous fluid 196.4 mg/dL, brain 22.0 mg/100 g, liver 21.2 mg/100 g, and kidney
      25.9 mg/100 g using a headspace gas chromatographic method. Significantly, no
      methanol was detected in samples recovered from the esophagus, stomach, duodenum,
      small intestine, bile, or urine. These findings are inconsistent with either
      recent or delayed oral ingestion of methanol. We concluded that absorption of
      methanol occurred dermally and through the oral mucosa as she lay dying and
      saturated in the fuel additive. Based upon the toxicological data and a
      comprehensive forensic investigation (including documentation and analysis of
      evidence recovered at the scene and the autopsy), the cause of death was
      determined to be blunt impact trauma and methanol poisoning.

PMID- 16419411
TI  - Over-the-counter cold medications-postmortem findings in infants and the
      relationship to cause of death.
AB  - The Montgomery County Coroner's Office has encountered a series of 10 infant
      deaths over an 8-month period in infants under 12 months old with toxicology
      findings that include a variety of drugs commonly found in over-the-counter (OTC)
      cold medications. The drugs detected were ephedrine, pseudoephedrine,
      dextromethorphan, diphenhydramine, chlorpheniramine, brompheniramine, ethanol,
      carbinoxamine, levorphanol, acetaminophen, and the anti-emetic metoclopramide.
      Toxicology findings were confirmed in 2 different matrices in 9 of the 10 cases
      and by 2 different analytical methods. The blood concentrations of the drugs and
      the case histories, as well as the cause of death for each infant, if available,
      will be given. The majority of these deaths were either toxicity from the OTC
      cold medications directly or as a contributory factor in the cause of death. Only
      two of the cases were the result of possible child abuse. Caregivers may be under
      the mistaken notion that OTC cold medications formulated for children are also
      safe for use in infants. These cases demonstrate that not only is administration
      of some OTC cold medications not safe, but use of OTC cold medications in infants
      can result in toxicity that can lead to death.

PMID- 16419412
TI  - Apparent suicidal carbon monoxide poisonings with concomitant prescription drug
      overdoses.
AB  - We report four separate suicides by apparent motor vehicle-related carbon
      monoxide (CO) poisoning in which complete toxicological analysis showed the
      absence of, or lower than expected, percent carboxyhemoglobin saturation and high
      concentrations of concomitant prescription drugs. These cases, within a
      population of 71 apparent CO suicides from the Wayne County Medical Examiner's
      Office over 1998-2004, represent cases where additional factors are in play.
      Multiple modalities (CO poisoning and drug overdose) and/or undetectable carbon
      dioxide poisoning from the vehicle exhaust of cars manufactured after laws
      regulating vehicle emissions were enacted are examples of additional factors that
      require consideration in these selected cases. All four cases demonstrated some
      degree of decomposition, so the possible loss of CO could not be ruled out. The
      need for full toxicological analysis in apparent suicidal CO poisoning is
      emphasized.

PMID- 16419413
TI  - Tissue distribution of loperamide and N-desmethylloperamide following a fatal
      overdose.
AB  - We report a case involving a fatal intoxication with loperamide (Imodium).
      Loperamide is a synthetic opioid of the phenyl piperidine class used as an over
      the-counter antidiarrheal. It exerts its effects through interaction with micro
      opiate receptors in the intestine to reduce peristalsis. Loperamide lacks the
      typical euphoric opiate effects when administered at recommended doses. Both
      loperamide and its major metabolite, N-desmethylloperamide, were isolated by
      liquid-liquid extraction into n-butyl chloride from alkalinized samples. Extracts
      were analyzed by liquid chromatography-electrospray-mass spectrometry in selected
      ion-monitoring mode. Rapid separation of the drug, metabolite, and internal
      standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8
      microm particle diameter. The mobile phase consisted of 0.1% formic acid in
      deionized water (60%) and acetonitrile (40%) at a flow rate of 0.5 mL/min. Heart
      blood concentrations for loperamide and its metabolite were 1.2 mg/L and 3.3
      mg/L, respectively. In contrast, reported peak plasma concentrations of
      loperamide after administration of recommended daily doses of 16 mg did not
      exceed 0.012 mg/L in controlled trials. Because the heart blood ethanol
      concentration was 0.08 g/dL, the medical examiner ruled that the cause of death
      was loperamide and ethanol intoxication, and the manner of death as undetermined.

PMID- 16419414
TI  - Fatal seizures due to potential herb-drug interactions with Ginkgo biloba.
AB  - Alternative therapy including herbal drugs and complementary medicine is becoming
      increasingly popular. However, the rise in the incidence of herb-drug
      interactions is causing concern, especially in the absence of warning labels
      addressing potential adverse effects. We present the case of a 55-year-old male
      who suffered a fatal breakthrough seizure, with no evidence of non-compliance
      with his anticonvulsant medications. The autopsy report revealed subtherapeutic
      serum levels for both anticonvulsants Depakote and Dilantin. Concomitant with his
      prescribed medications, the decedent was also self-medicating with a cornucopia
      of herbal supplements and nutraceuticals, prominent among which was Ginkgo
      biloba. Ginkgo, an herbal extract from the leaves of the Ginkgo biloba tree, has
      been used medicinally for centuries and has been touted as a cure for a variety
      of medical conditions. The induction of Cytochrome P450 enzymes by components of
      herbal drugs has been known to affect the metabolism of various drugs. Dilantin
      is primarily metabolized by CYP2C9, and secondarily metabolized by CYP2C19.
      Valproate metabolism is also modulated in part by CYP2C9 and CYP2C19. A recent
      study revealed significant inductive effect of ginkgo on CYP2C19 activity.
      CYP2C19 induction by ginkgo could be a plausible explanation for the
      subtherapeutic levels of Dilantin and Depakote. Additionally, ginkgo nuts contain
      a potent neurotoxin, which is known to induce seizure activity. Evidence of other
      herbal drugs diminishing the efficacy of anticonvulsant medication does exist;
      however, there has been only one other documented instance of ginkgo potentiating
      seizure activity in the presence of anticonvulsant therapy. Highlighting the
      potential adverse effects and drug interactions of ginkgo on the packaging of the
      drug may help prevent inadvertent use in vulnerable individuals.

PMID- 16419415
TI  - Determination of l-methamphetamine: a case history.
AB  - Methamphetamine was detected in a 77-year-old male who had a history of
      congestive heart failure. Using a modification of a previously reported method,
      trifluoroacetyl-l-prolyl chloride was used to derivatize sympathomimetic amines
      to allow separation and identification of individual enantiomers. The l
      enantiomer of methamphetamine and a trace amount of l-amphetamine were found in
      blood and urine specimens from this case. Further investigation revealed the
      decedent had bronchial asthma and regularly used a Vicks Inhaler, which contains
      l-methamphetamine as the active ingredient.

PMID- 16419416
TI  - Elevated postmortem ethanol concentrations in an insulin-dependent diabetic.
AB  - A 54-year-old woman (165 cm, 37 kg) was found dead in her home during a welfare
      check after not having been seen for at least three days. The body showed clear
      evidence of decomposition. Her head was in what appeared to be a pool of blood.
      The residence was clean, neat, and showed no evidence of violence. Insulin was
      found in the refrigerator, and syringes were in the kitchen cabinet. In agreement
      with these physical findings, her clinical history indicated that she suffered
      insulin-dependent diabetes mellitus. Autolytic changes were noticed at autopsy,
      and no obvious cause of death was demonstrated. The autopsy heart blood sample
      screened negative for cocaine and/or metabolite (benzoylecgonine),
      phenethylamines, opiates, and barbiturates by radioimmunoassay. The alcohol
      concentration was 0.51 g/dL in the blood, 0.04 g/dL in the brain, 0.08 g/dL in
      the liver, and 0.05 g/dL in the urine, and acetone levels were 42 mg/dL, 53
      mg/dL, 14 mg/dL, and 19 mg/dL, respectively. Isopropanol was also present in all
      samples analyzed. The cause of death was ruled as metabolic acidosis due to
      diabetes mellitus. Possible bacterial postmortem production of ethanol is
      considered as an explanation for the increased concentration of ethanol found in
      the postmortem heart blood.

PMID- 16419417
TI  - Detection of smoked cocaine marker (anhydroecgonine methylester) in nails.

PMID- 16419418
TI  - Photodynamic therapy for inflammatory CNV: do we know enough?

PMID- 16419419
TI  - Immunomodulatory therapy for ocular inflammatory disease: a basic manual and
      review of the literature.
AB  - Corticosteroids are used as first-line treatment for many ocular inflammatory
      conditions. The risk of adverse effects, however, necessitates conversion to
      steroid-sparing immunomodulatory therapy (IMT) for disease that is recurrent,
      chronic, or poorly responsive to treatment. Combination drug treatments with
      multiple agent 'recipes' are also considered. Immunomodulatory agents include the
      broad categories of antimetabolites (azathioprine, methotrexate, mycophenolate
      mofetil), alkylating agents (cyclophosphamide, chlorambucil), T-cell inhibitors
      (cyclosporine, tacrolimus), and cytokines (interferon alfa). This article reviews
      and summarizes the evidence for IMT agent use in the treatment of various forms
      of ocular inflammation.

PMID- 16419420
TI  - Outcomes of treatment with immunomodulatory therapy in patients with
      corticosteroid-resistant juvenile idiopathic arthritis-associated chronic
      iridocyclitis.
AB  - PURPOSE: To describe the clinical outcome of patients with juvenile idiopathic
      arthritis (IA)-associated chronic iridocyclitis unresponsive to conventional
      therapy, in whom inflammation was eventually controlled using immunomodulatory
      therapy (IMT), and to determine if patients treated early with IMT have better
      visual acuity outcomes than those treated with corticosteroid alone. METHODS:
      Patients with JIA-associated chronic iridocyclitis receiving immunomodulatory
      therapy at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and
      Ear Infirmary between 1981 and 2001 were studied. INCLUSION CRITERIA: JIA with
      chronic corticosteroid-dependent uveitis; IMT for a minimum of one year; minimum
      follow-up of three years; inflammation eventually controlled for a minimum of six
      consecutive months by IMT. RESULTS: At last visit, 51% of eyes (23 eyes) had
      acuity of 20/20 to 20/40, 16% (7 eyes) had 20/50 to 20/100, and 33% (15 eyes) had
      20/200 or less. In patients whose chronic inflammation was eventually controlled
      within three years from onset of the uveitis, final bilateral vision was
      maintained within 20/20 to 20/30, except for a patient whose one eye had poor
      vision at initial consultation. When acuities at the end of the follow-up period
      of patients treated early with IMT were compared with acuities at the initial
      consultation of patients treated late with IMT, with duration of uveitis matched
      for each patient, visual acuities of those treated early were statistically
      significantly better than those treated late with IMT (p < 0.005 right and left
      eyes pooled; p = 0.0075 best eyes; p = 0.0375 worst eyes). CONCLUSIONS: We noted
      improvement or maintenance of visual acuity (86%) during the course of follow-up
      of patients with treatment-resistant JIA-associated uveitis treated with
      effective IMT. However, only IMT given early in the disease course was noted to
      be associated with bilateral visual acuity of 20/30 or better.

PMID- 16419421
TI  - Photodynamic therapy for subfoveal classic choroidal neovascularization related
      to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis-like
      syndrome (POHS-like).
AB  - PURPOSE: To evaluate the safety and efficacy of photodynamic therapy with
      verteporfin (PDT) for subfoveal classic choroidal neovascularization (CNV)
      related to punctate inner choroidopathy (PIC) or presumed ocular histoplasmosis
      like syndrome (POHS-like). METHODS: Retrospective review of 16 eyes from 14
      patients with subfoveal classic CNV associated with PIC or POHS-like and treated
      with PDT. RESULTS: The mean visual acuity increased from 4.5/10 (range: 1/10
      9/10) to 7/10 (range: 2/10-10/10) after a mean follow-up of 21 months (range: 8
      32 months) and a mean number of 2 PDT (range: 1-6). Visual acuity remained stable
      or improved in 13 of the 16 eyes (81%) and decreased in three. CONCLUSION: This
      nearly two-year follow-up study suggests that PDT could be helpful for patients
      with subfoveal classic CNV related to PIC or POHS-like.

PMID- 16419422
TI  - Clinical features and outcomes of HLA-b27-positive and HLA-B27-negative acute
      anterior uveitis in a Turkish patient population.
AB  - PURPOSE: To compare the clinical features and outcomes of HLA-B27-positive and
      HLA-B27-negative acute anterior uveitis (AAU) in a large Turkish patient
      population. METHODS: Forty-four patients with HLA-B27-positive AAU and 65 with
      HLA-B27-negative AAU were reviewed retrospectively. HLA-B27 typing, gender,
      laterality, clinical features (fibrinous reaction, hypopyon formation), ocular
      complications, medical treatment, and final visual acuity were recorded.
      Statistical analyses included Student's t-test, Fisher's exact test, Yate's
      corrected Chi2 test, and Mann-Whitney U test. A p-value of <0.05 was considered
      statistically significant. RESULTS: Forty percent of all patients with AAU were
      found to be positive for HLA-B27 antigen. HLA-B27-positive AAU was significantly
      more common in males and HLA-B27-negative AAU in females. Unilateral or bilateral
      alternating AAU as well as fibrinous reaction and hypopyon formation were more
      common in HLA-B27-positive patients. Posterior iris synechiae and cataract
      formation were more common and systemic immunosuppressive agents were exclusively
      required in patients with HLA-B27-negative AAU. Visual outcome did not differ
      significantly between the HLA-B27-positive and HLA-B27-negative groups.
      CONCLUSIONS: HLA-B27 association is less common in Turkish patients with AAU than
      in other populations reported in the literature. Although distinct features of
      HLA-B27 uveitis were confirmed in our study, visual outcome did not differ from
      idiopathic AAU. Therefore, we believe that HLA-B27 typing in patients with AAU
      helps the clinician with the diagnosis. However, it has a limited value in
      determining the prognosis.

PMID- 16419423
TI  - The efficacy of hyperbaric oxygen for the treatment of experimental uveitis
      induced in rabbits.
AB  - OBJECTIVE: The aim of the present study was to examine the efficacy of hyperbaric
      oxygen (HBO) therapy in the treatment of experimental uveitis induced in rabbits.
      It was hypothesized that HBO therapy improves the regression of experimental
      uveitis induced in rabbits. RESEARCH DESIGN AND METHODS: An experimental animal
      study was conducted on 48 rabbits (48 right eyes of these rabbits) to evaluate
      the effects of HBO therapy on endotoxin-induced acute anterior uveitis in
      rabbits. To induce acute anterior uveitis, Salmonella typhimurium
      lipopolysaccharide endotoxin (LPS) was intravitreally injected into the right
      eyes of the rabbits. The animals were randomly assigned to five groups. No
      treatment was given to the rabbits in Group A. Prednisolone acetate was topically
      administered to the rabbits in Group B. Methylprednisolone acetate was
      administered by anterior subtenon injection to the rabbits in Group C four hours
      after LPS application. HBO therapy was administered to the rabbits in Group D.
      Both HBO therapy and anterior subtenon injection of methylprednisolone therapy
      were administered to the rabbits in Group E. To compare the effects of the
      different therapies on the progression of endotoxin-induced uveitis, examinations
      including clinical scoring of anterior uveitis, microscopic examination of
      aspirated aqueous humor for inflammatory responses, and aqueous protein level
      assessment were performed once a day after LPS injection. RESULTS: There was a
      statistically significant difference between the control group (Group A) and
      other groups (Groups B-E) with respect to the number of inflammatory cells and
      protein levels in the aqueous one and three days after LPS injection (p < 0.05),
      indicating that the treatments resulted in less inflammation in Groups B-E
      compared to Group A. Moreover, there was no statistically significant difference
      between Groups B and C, Groups B and D, Groups B and E, Groups C and D, and
      Groups C and E with regard to the number of inflammatory cells in the aqueous at
      Day 1 after LPS injection (p > 0.05). In addition, Groups B and C and Groups B
      and D were comparable with regard to cell counts at Day 3 (p > 0.05), showing
      that HBO was comparable to corticosteroids in reducing inflammation. The
      differences between Groups B and E and Groups C and E were significant with
      regard to aqueous cell counts at Day 3 (p < 0.05), showing that HBO plus steroid
      was more effective than steroids alone. CONCLUSION: The intensity of ocular
      inflammation in the group receiving HBO therapy combined with anterior subtenon
      injection of methylprednisolone therapy was lower than in the other groups. We
      also demonstrated that HBO therapy was an effective therapeutic modality for the
      treatment of experimental uveitis induced in rabbits with an efficacy comparable
      to that of corticosteroids. Moreover, HBO plus steroid was superior to steroids
      alone in reducing inflammation.

PMID- 16419424
TI  - Eyelid skin involvement in pemphigus foliaceus.
AB  - PURPOSE: To report the involvement of eyelid skin in a patient with pemphigus
      foliaceus. METHODS: Retrospective, interventional case report of a patient with
      pemphigus foliaceus involving both eyelids. The diagnosis of pemphigus foliaceus
      was based on histopathology and confirmed by direct immunofluorescence and
      immunoblot. Failure to respond to conventional immunosuppressive therapy,
      including high-dose corticosteroids, methotrexate, azathioprine, dapsone, and
      mycophenolate mofetil, necessitated the use of intravenous immunoglobulin (IVIg)
      therapy. RESULTS: After successful treatment with IVIg, no change in visual
      acuity or other sequelae secondary to ocular pemphigus foliaceus were observed.
      Normal ocular architecture was maintained. Clinical remission was observed after
      successful therapy. CONCLUSIONS: Pemphigus foliaceus involves the skin of the
      eyelid and does not involve the conjunctiva. The patient did not respond to
      conventional immunosuppressive therapy. The use of IVIg as mono-therapy resulted
      in long-term clinical remission.

PMID- 16419425
TI  - A rare ocular complication of mumps: kerato-uveitis.
AB  - PURPOSE: To report a child who developed kerato-uveitis associated with mumps
      infection. METHODS: A prospective study of a child who was observed at the
      Department of Ophthalmology, Marmara University, Faculty of Medicine, during
      spring 2003. RESULTS: An 11-year-old male patient noticed decreased vision in his
      left eye. His right eye was completely normal. Visual acuity was perception of
      hand movements in the left eye. Ocular examination revealed ciliary injection and
      diffuse hyperemia of the conjunctiva, interstitial keratitis characterized by
      prominent stromal infiltrates and edema, folds in the Descemet's membrane, and
      microcystic epithelial edema in his left eye. The patient had been diagnosed as
      having mumps 10 days previously by a pediatrician. Complete recovery of the
      keratitis occurred on the 10th day of topical steroid treatment. CONCLUSIONS:
      Keratitis and/or iritis are rare complications of mumps. Corneal involvement is
      characterized by unilateral and painless interstitial keratitis that may cause a
      significant decrease in vision. Keratitis resolves with treatment and does not
      have any sequelae.

PMID- 16419426
TI  - Eyelid swelling as the only manifestation of ocular sarcoidosis.
AB  - PURPOSE: To describe a case of eyelid sarcoidosis without systemic manifestations
      with a three-year follow-up. METHODS: A 73-year-old woman presented complaining
      of a one-year history of swelling and hyperemia in the right upper eyelid. To
      confirm the diagnosis, we performed an incisional biopsy of the eyelid. RESULTS:
      Histopathological examination showed a non-caseating granulomatous process
      suggestive of sarcoidosis. After three years, the patient was asymptomatic and
      physical and laboratory examination showed no signs of systemic sarcoidosis.
      CONCLUSION: The histopathological exam was fundamental for the diagnosis.

PMID- 16419427
TI  - Bilateral uveitis manifesting as a complication of chronic graft-versus-host
      disease after allogeneic bone marrow transplantation.
AB  - PURPOSE: To document the rare occurrence of uveitis presumed secondary to chronic
      graft-versus-host disease (cGVHD). METHODS: Observational case report. RESULTS: A
      52-year-old Filipino male who had undergone allogeneic BMT 10 years earlier
      presented with bilateral uveitis and biopsy-proven cutaneous cGVHD. There was no
      evidence of infection or other immune-related causes and the inflammation had a
      temporal correlation with his dermatological GVHD. The patient responded to
      treatment with oral cyclosporin A. CONCLUSION: The coexistence of uveitis and
      cGVHD is rare. The ophthalmologist should be aware of such an association and
      work together with the oncologist to treat these patients appropriately.

PMID- 16419428
TI  - Macular retinitis as a first sign of subacute sclerosing panencephalitis: the
      importance of early diagnosis.
AB  - PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a subacute inflammatory
      and neurodegenerative encephalitis related to the measles (rubeola) virus and
      usually affecting children and young adults. The overwhelming majority of cases
      follow a progressive downhill course leading to death, although there have been a
      few case reports of patients who have apparently gone into remission. Ocular
      changes occur in up to 50% of SSPE cases. Visual complaints, if present,
      generally antedate the onset of neurological symptoms by a few weeks or months.
      Here, we report two cases of SSPE presenting with ocular findings and their
      prognoses. METHODS: Case reports. In the first case, a 17-year-old male
      presenting with macular retinitis, the macular findings were mistaken for a
      heredodegenerative disorder and diagnosis was postponed until neurological
      findings took place. He died six months after the appearance of his first
      ophthalmic symptoms despite intravenous immune globulin and isoprinosine therapy.
      The second case was a 14-year-old male, who presented with only ophthalmological
      complaints. His diagnosis was based on both ophthalmological findings and high
      doses of measles IgG in the cerebrospinal fluid (CSF); isoprinosine and
      intramuscular beta-interferon therapy was started before the onset of
      neurological findings and in the follow-up time of about 18 months, neurological
      findings consistent with SSPE did not develop. RESULTS: The characteristic
      finding of macular retinitis in SSPE patients is rapid recovery in about one
      month without therapy. After improvement, neurological findings take place. Once
      suspected, the diagnosis of SSPE is easily established by the demonstration of
      high levels of measles antibody in the serum and CSF. Early diagnosis can be made
      with typical ocular findings and high IgG titers for rubeola in CSF. CONCLUSION:
      We suppose that ophthalmic manifestations, especially macular retinitis, may be
      useful in the diagnosis and management of SSPE cases with elevated IgG titers for
      rubeola in CSF. The typical clinical findings must be familiar to every
      ophthalmologist so that diagnostic pitfalls can be prevented and early therapy
      started. It may be discussed if early diagnosis and therapy will be possible
      before neurological signs appear, the prognosis of this relentless disease may
      show a more favorable course.

PMID- 16419429
TI  - Immunohistochemical expression of p63 in human prenatal tooth primordia.
AB  - The aim of this study was to investigate the expression of the p63 gene in normal
      human tooth buds at different gestational stages. This is the first detailed
      study of p63 expression in normal human prenatal tooth primordia. The material
      consisted of sections of the midaxial tissue block from the cranial base of three
      human fetuses of gestational ages (GA) 11, 15, and 21 weeks. The sections
      included tooth primordia representing cap stages and bell stages of human tooth
      morphogenesis. In the present study, immunostaining was carried out using the
      primary antibody, monoclonal mouse anti human p63 protein, clone 4A4. The
      sections were counterstained with hematoxylin Mayer. p63 immunoreactivity was
      identified by microscopy. The study showed a positive reaction of p63 in both the
      cap stage and the bell stage. In both stages, positivity was observed in the
      cells of the oral mucosa, the inner and outer enamel epithelium, and in the
      primary and secondary dental lamina. In the early cap stage, there is a strong
      positive reaction to p63 in the enamel knot, but not in the late cap stage. We
      suggest that p63 may have an important regulatory function in the enamel knot.

PMID- 16419430
TI  - Dental fluorosis and dental caries in permanent teeth: rural schoolchildren in
      high-fluoride areas in the Shaanxi province, China.
AB  - OBJECTIVES: To study the dental fluorosis and caries in the permanent teeth of 12
      to 13-year-old children in fluorosis-endemic areas; to assess the relationship
      between fluorosis and the fluoride content of the drinking water and the
      relationship between caries and the fluoride content of the water; finally, to
      analyze the effect of fluoride intake and water stored in clay pots on dental
      fluorosis. MATERIAL AND METHODS: 477 children were divided into 5 groups (A to E)
      according to the fluoride concentration of the waters, i.e. by 0.4, 1.0, 1.8,
      3.5, and 5.6 mg F/l, respectively. Dental fluorosis was assessed by TF score and
      caries by the DMF-T index. A questionnaire was used to obtain information about
      water storage and other information relevant to children's fluoride intake.
      RESULTS: A positive relationship was found between the mean TF scores and the
      water fluoride concentration. In groups B and D, the TF score was higher in 13
      year-olds than in 12-year-olds. Caries prevalence and mean DMF-T ranged from 2.6%
      and 0.03 (group E) to 22.1% and 0.38 (group A). Storage of water in clay pots
      seemed to increase the severity of fluorosis slightly, and to decrease the caries
      prevalence. CONCLUSIONS: Defluoridation of drinking water, or--alternatively--the
      provision of low-fluoride water sources, should be given high priority in the
      examined Shaanxi rural areas. Fluoride concentration of drinking water should be
      maximum 0.6 mg/l. Storage of water in the local clay pots may increase the
      severity of dental fluorosis.

PMID- 16419431
TI  - Short-term antidepressant treatment of comorbid dental anxiety in patients with
      panic disorder.
AB  - OBJECTIVES: The aims of this study were to determine the frequency of dental
      anxiety (DA) and dental phobia (DP) in panic disorder, and to follow the changes
      in DA levels during antidepressant treatment of panic disorder. METHODS: Fifty
      three controls and 102 panic disorder patients were assessed using the Structured
      Clinical Interview (SCID), the Panic-Agoraphobia Scale (PAS), and the Corah
      Dental Anxiety Scale (DAS). Oral health status was defined by the number of
      decayed, missing, and filled teeth (DMFT) index. The patients were classified
      into three groups: (1) those without dental anxiety (WDA), (2) those with dental
      anxiety (DA), and (3) those with dental phobia (DP). All patients were treated
      with antidepressants for 3 months and the response rates were assessed. RESULTS:
      At baseline, DAS was significantly higher in both the DA and the DP groups than
      in the control group. Ten (9.8%) of the panic disorder patients fulfilled the
      diagnostic criteria for DP; 31 (30.4%) had severe DA. In the control group, none
      of the patients was diagnosed as DP, whereas 7 (13.5%) had severe DA. Panic
      disorder and DA both responded to the antidepressant treatment, but DAS scores
      remained significantly higher in the DP group than in the DA group and the
      control group at the end of the third month. CONCLUSIONS: Our data suggest that
      both DA and DP are more frequent in panic disorder than in healthy controls.
      Antidepressant treatment may have been helpful in decreasing DA levels in the DA
      group but not in the DP group.

PMID- 16419432
TI  - Bonding of ceramic insert to a laboratory particle filler composite.
AB  - The push-out bond strength of cylindrical ceramic inserts (CI) to particulate
      filler resin composite (VC) was evaluated in this study. Various surface
      treatments to improve the adhesion of CI to resin composite were tested.
      Additionally, the effect of fiber-reinforced composite (FRC) laminate
      encapsulation around CI was tested. Feldspathic porcelain CI with a diameter of
      3.1 mm was bonded to VC. Adhesive resin was used for bonding. In group 1, no
      surface treatment of CI was done. In group 2, CI was encapsulated with a thin
      layer of woven glass FRC. In group 3, the surface of the CI was tribochemically
      silica coated and silanized. In group 4, the surface of the CI was grit-blasted
      with 50 microm aluminum oxide and etched with hydrofluoric acid. In group 5, the
      grit-blasted CI was encapsulated with a layer of FRC. The specimens (n = 6/group)
      were either dry stored or thermocycled in water (6000 x 5-55 degrees C). The push
      out test was carried out with a universal material testing machine. The highest
      push-out strength was achieved in group 5 (20.4 MPa) and the lowest in group 2
      (11.5 MPa). ANOVA revealed that both surface treatment and storage condition had
      a significant effect on push-out strength (p < 0.05). We conclude that the
      additional glass FRC encapsulation can be used to increase the bond strength of
      insert to composite.

PMID- 16419433
TI  - Public dental health care program for persons with disability.
AB  - The objectives of the study were (1) to describe the organization and content of
      the Danish public oral health care program for persons with disability, and (2)
      to analyse possible variations in relation to the goals and requirements set by
      the health authorities. Data were collected by means of self-administered
      questionnaires completed by the person responsible locally for the program in
      each municipality. The response rate was 84%. The following topics were included:
      (1) Number of persons attending the program, (2) procedure for identification of
      persons eligible for the program, (3) payment of service, (4) providers of oral
      health care, (5) special training of staff, 6) dental services delivered, (7)
      ethical issues, and (8) patient rights. Less than one-third of persons estimated
      by the health authorities were enrolled in the program. On average, 0.4% of the
      municipal population attended the program, ranging from 0.03% to 1.53%. In large
      municipalities, and where internal providers delivered oral health care,
      relatively more persons were enrolled in the program (p < 0.001). Overall, more
      than 20 categories of personnel were involved in the selection procedure;
      attitude and lack of knowledge of oral health and oral health care for persons
      with disability were barriers to equal access to the program. Preventive dental
      services were the most frequent services delivered, although relatively few oral
      hygienists were involved in the program. Special training was most frequent in
      large municipalities. To secure equal access for persons with disability, it is
      recommended that joint collaboration between smaller municipalities should be
      made regarding procedures of such programs. Special training of dental personnel
      and of the staff responsible for selecting persons for the program should be
      systematically organized at a higher administrative level. The pattern of dental
      services delivered justifies further involvement of oral hygienists in the
      program.

PMID- 16419435
TI  - Wear of teeth due to occupational exposure to airborne olivine dust.
AB  - OBJECTIVES: To clarify whether high tooth wear of employees in a mining industry
      that extracts the mineral olivine could be associated with airborne dust exposure
      in their working environment. METHOD: The cumulative exposure to airborne mineral
      dust for the workers in the company was calculated on the basis of their period
      of employment multiplied by the airborne olivine-dust concentrations, which have
      been monitored continuously during the past 20 years for all divisions of the
      company. After invitation, 85% of the employees (n = 191) were examined
      clinically and their dentitions were photographed and duplicated in plaster
      casts. Four clinicians, working independently, examined the sets of
      casts/photographs for tooth wear and ranked these from most to least. Two groups
      of employees were compared with regard to tooth wear, i.e. the 30% with the
      highest (case) and the lowest (control) estimated dust exposure levels. Tooth
      wear in the case and control groups was compared using a non-parametric test
      based on rankings (Mann-Whitney test). RESULTS: Tooth wear differed significantly
      between the workers in the low and the high mineral dust exposure groups (p <
      0.001). The differences were also apparent within three age subsets, although
      statistical significance was reached only in the 34-44 years subset (p = 0.002).
      Considerable individual variation was noted within the three exposure groups.
      CONCLUSION: Workers with high exposure to airborne olivine dust may contract
      considerable tooth wear.

PMID- 16419436
TI  - Adolescents' views of oral health education. A qualitative study.
AB  - The objective of this study was to investigate adolescents' perceptions and
      desires with respect to oral health education. A series of focus group sessions
      was conducted with adolescents in schools. The groups comprised an average of 6
      individuals, with a total of 34 participants. The main themes of the discussions
      were the informants' perceptions of the oral health education in different
      settings and under varying circumstances. The discussions were transcribed
      verbatim and analyzed according to the basic principles of Grounded Theory. One
      of the most important issues appeared to be the dental personnel considering the
      individual as a subject and not as an object. The adolescents in the study were
      uncertain about their knowledge of oral health. Often, the participants expressed
      a wish to be taught more at the dental visit. Information in schools was sparse.
      The support of parents was acknowledged but little discussed. The methods used in
      advertisements to describe dental products were met with skepticism. These should
      not be imitated in oral health education as this might undermine the credibility
      of the dental services. Girls were perceived to be more interested in health than
      boys were. Two core categories labeled "credibility" and "confidence", which
      interacted continually, emerged from the data in the analysis. The results
      indicate that the credibility of the intermediary of the health messages is
      essential, as is their ability to create confidence. Thus, oral health education
      among adolescents is more likely to be successful when credibility and confidence
      are perceived.

PMID- 16419434
TI  - Oral and salivary parameters in patients with rheumatic diseases.
AB  - We studied the presence of secondary Sjogren's syndrome (SS) and the composition
      of saliva, prevalence of oral pathogens, periodontitis, mouth mucosa, and teeth
      in patients with various rheumatic diseases and in healthy controls. The
      hypothesis was that different rheumatic diseases might cause differences in oral
      health characteristics because of the liability of secondary SS in the patients.
      The study involved 77 patients and 77 age-matched and sex-matched controls.
      Twenty patients were suffering from spondylarthropathy (SPA), 18 from ankylosing
      spondylitis (AS), 24 from rheumatoid arthritis (RA), and 15 from mixed connective
      tissue disease (MCTD). Clinical and radiographic oral health status was recorded
      and salivary flow rates were measured. Selected salivary proteins and
      immunoglobulins were analysed by routine methods. Minor salivary gland biopsy
      samples were taken from the patients for assessment of inflammatory focus scores.
      Differences between patients and controls and in between the different rheumatic
      diseases were analysed statistically. Secondary SS was diagnosed in 39% (30/77)
      of the patients. A severe periodontal condition (community periodontal index of
      treatment needs score 3 or 4) occurred in 58% (45/77) of the rheumatic patients
      compared with only 26% (20/77) of the controls (p < 0.0001). The severity of
      focal sialadenitis (focus score) correlated significant with salivary IgA, IgG,
      and IgM concentrations. Salivary albumin, total protein, IgG, and IgM
      concentrations were higher in all patient groups than in the controls. The number
      of patients with low salivary flow rates was higher in all patient groups
      compared to controls. Oral yeast counts were significantly higher in the patients
      than in the controls (p < 0.001). In a subgroup analysis, patients with SS had
      higher values for salivary IgA and IgM than patients without SS. Dental caries
      and oral lactobacilli were more frequent in patients with SS, but SS was not
      associated with periodontitis. No major differences were noted in other salivary
      biochemical parameters between these two groups. Patients with rheumatic
      diseases, irrespective of specific diagnosis, thus had various alterations in
      salivary flow and composition and oral health. The findings may reflect the
      autoimmune inflammation of the salivary glands frequently observed in these
      patients.

PMID- 16419437
TI  - Relationships between occlusal or free-smooth and approximal caries in mixed
      dentition.
AB  - This cross-sectional study aimed to examine the relationships between free-smooth
      or occlusal surfaces and approximal caries in 104 schoolchildren between 6 and 8
      years of age. Caries diagnosis was clinically and radiographically assessed, and
      white spot lesions, evident caries lesions or restorations, as well as
      radiolucence in enamel were considered to be caries. In the studied subjects, the
      correlations were analyzed in the 1st primary molars (Ds), the 2nd primary molars
      (Es), the 1st permanent molars (6s), and all molars. The data were statistically
      analyzed by chi-square test. Significant correlations between occlusal surface
      caries and approximal surface lesions were observed in Ds and Es teeth and in all
      molars, but not for 1st permanent molars. For free-smooth surface, these
      correlations were significant only for Es and all molars. Sensitivity and
      specificity for occlusal surface as an indicator of approximal caries in the same
      tooth type ranged from 73% to 83% and 51% to 58%, respectively. Similarly, for
      free-smooth surface the values varied from 22% to 60% and 57% to 90%,
      respectively. Sensitivity and specificity for occlusal surface caries in
      identifying subjects with approximal caries were 78% and 70%, respectively; for
      free-smooth surface, the corresponding values were 59% and 65%, respectively. The
      results suggest that visually detected caries lesions are indicative of
      approximal caries. Thus, if a certain risk limit is defined and the corresponding
      number of caries lesions in different surfaces is reached, the risk is above the
      threshold and could be a practical guideline on the need for radiography in this
      age group of patients with "moderate caries experience".

PMID- 16419438
TI  - Xylitol-resistant mutans streptococci strains and the frequency of xylitol
      consumption in young children.

PMID- 16419439
TI  - Lying and cheating: fraudulent excuse making, cheating, and plagiarism.
AB  - Undergraduates reported their use of fraudulent excuses; 72% of the student
      participants claimed to have used a fraudulent excuse in college at least once.
      This activity was correlated with an independently obtained self-report measure
      of cheating (r = .38) and plagiarism (r = .27). Grade point average was
      negatively correlated with all 3 measures but did not reach statistical
      significance with the measure of plagiarism.

PMID- 16419440
TI  - Tacit knowledge in academia: a proposed model and measurement scale.
AB  - The authors propose a multidimensional model of tacit knowledge and develop a
      measure of tacit knowledge in academia. They discuss the theory and extant
      literature on tacit knowledge and propose a 6-factor model. Experiment 1 is a
      replication of a recent study of academic tacit knowledge using the scale
      developed and administered at an Israeli university (A. Somech & R. Bogler,
      1999). The results of the replication differed from those found in the original
      study. For Experiment 2, the authors developed a domain-specific measure of
      academic tacit knowledge, the Academic Tacit Knowledge Scale (ATKS), and used
      this measure to explore the multidimensionality of tacit knowledge proposed in
      the model. The results of an exploratory factor analysis (n=142) followed by a
      confirmatory factor analysis (n=286) are reported. The sample for both
      experiments was 428 undergraduate students enrolled at a large public university
      in the eastern United States. Results indicated that a 5-factor model of academic
      tacit knowledge provided a strong fit for the data.

PMID- 16419441
TI  - Communal versus individual learning of a math-estimation task: African American
      children and the culture of learning contexts.
AB  - The authors compared the performance of 78 African American 5th-grade students
      who studied a math-estimation task in one of two learning contexts. Learning
      contexts differed in the degree to which they afforded the expression of
      communalism. ANCOVA confirmed that posttest performance was best for students who
      studied in the high communal-learning context. The findings support A. W.
      Boykin's (1994) contention that the cultural context of learning can be a
      critical mediator of children's performance.

PMID- 16419442
TI  - Personality attributes as predictors of psychological well-being for NCOs.
AB  - The authors examined the nature of the relationships between job-specific
      personality dimensions and psychological well-being for noncommissioned officers
      (NCOs) in the Turkish Armed Forces (TAF). A job-specific personality inventory,
      comprising measures of 11 personality dimensions was developed for selection
      purposes. The inventory was administered to a representative sample of 1,428 NCOs
      along with a general mental health inventory developed by the authors, which
      consisted of 6 dimensions of psychological well-being. Exploratory and
      confirmatory factor analyses suggested existence of a single factor underlying
      the 6 psychological well-being dimensions, Mental Health, and 2 latent factors
      underlying the 11 personality dimensions, Military Demeanor and Military
      Efficacy. The 2 personality constructs explained 91% of the variance in the
      Mental Health construct. A stepwise regression indicated that beta weights of the
      personality measures were significant except for military bearing, orderliness,
      and dependability. Results suggest that job-specific personality attributes were
      predictive of mental health. Implications of the findings for the selection of
      NCOs are discussed.

PMID- 16419443
TI  - The Eysenck Personality Questionnaire Brief Version: factor structure and
      reliability.
AB  - The short scale of the Eysenck Personality Questionnaire-Revised (EPQR-S; H. J.
      Eysenck & S. B. G. Eysenck, 1992) is a 48-item personality questionnaire
      primarily designed to measure an individual's level of extraversion (vs.
      introversion) and neuroticism. Although L. J. Francis, L. B. Brown, and R.
      Philipchalk (1992) created the Eysenck Personality Questionnaire Revised
      Abbreviated (EPQR-A), an even briefer version of the EPQR-S, the reliability
      coefficients of some of the measures have been less than satisfactory (S.
      Forrest, C. A. Lewis, & M. Shevlin, 2000). Because brevity and reliability are
      both extremely important, the author of the present study created a briefer
      version of the EPQR-S, more reliable than the EPQR-A, by making slight
      alterations in the item content as well as the response format of the EPQR-S. Two
      hundred and sixty eight participants completed the original EPQR-S and the 24
      item newly revised briefer version of the EPQR-S (EPQ-BV) twice. The findings
      revealed that the EPQ-BV has good internal consistency, test-retest reliability,
      and concurrent validity. A principal component analysis revealed a solution with
      factor loadings that accurately reflected the primary measures of the EPQR-S.
      These findings are discussed in relation to the psychometric properties of the
      EPQR-A and the original version of the EPQR-S.

PMID- 16419444
TI  - Forgiveness and social loneliness.

PMID- 16419445
TI  - Globalization and nursing.

PMID- 16419446
TI  - [Pregnancy, delivery and puerperium: beliefs and practices of midwives in San
      Luis Potosi, Mexico].
AB  - OBJECTIVE: To document the beliefs and practices of traditional midwifes in
      regard to pregnancy, delivery and puerperium. METHOD: Taking advantage of a
      training course for 160 local traditional midwives from the Media and Huasteca
      regions of San Luis Potosi State, Mexico. Two of the teacher-nurses interviewed
      25 of them, supported by a member of Nahuatl and Tenek communities. The
      participant's identity was kept anonymous and permit for publications of results
      was obtained by informed consent. RESULTS: Traditional midwifes practices are
      common in social groups lacking health services. Their role is not limited to
      delivery and includes nursing, prenatal and puerperium care, as well as emotional
      and affective support to delivering mothers and their families. In this study
      several myths and traditional therapies were registered. CONCLUSION: The
      traditional therapy and primary health care resources of the Nahuatl and Tenek
      midwifes are useful and harmless for the perinatal care.

PMID- 16419447
TI  - [Care practices on the resuscitation of newborns in the context of a delivery
      center].
AB  - Approximately 10 to 15% of the neonates present difficulties in adapting to extra
      uterine life, which requires ability and readiness from the professional to
      intervene properly. This is an observational, cross-sectional study aimed at
      describing the care practices on the resuscitation of the newborn in the Delivery
      Center of a public hospital in the city of Sao Paulo. Data were obtained from the
      observation of 100 assistances given by health care professional staff and were
      recorded on a check-list instrument. Meconium-amniotic fluid was found in 24
      (24.0%) births and 47 (47.0%) newborns were submitted to respiratory airways
      aspiration. Of these, 6.4% (3) had their trachea aspirated. 26 (26.0%) newborns
      were ventilated, 5 (19.2%) of which by mask plus positive pressure; 1 (1.0%)
      newborn was submitted to a chest compression. After the initial resuscitation
      procedures, 6 (6.0%) newborns were referred to the neonatal intensive care unit.

PMID- 16419448
TI  - [The meaning of hospitalization for the pre-school child: a theoretical model].
AB  - This study was aimed at comprehending the meaning of being hospitalized for pre
      school children. The theoretical references were the Symbolic Interactionism and
      Vygotsky's theory on the child's symbolic play. The methodological referential
      was the Theory Based on Data. Eleven children between the ages of 3 and 6 took
      part in the survey. The strategies for data collection were: participative
      observation, interviews with the children mediated by the Therapeutic Toy, and
      interviews with the mothers. The analysis of the data made possible the
      construction of the technical model Growing up with the mother's protective
      presence, which puts in evidence the vulnerability, the child's force and the
      protection given by the mother to face the mystery and the fear of
      hospitalization.

PMID- 16419449
TI  - [Undergraduate nursing students' knowledge and viewpoints on depression].
AB  - This study aimed at identifying viewpoints, knowledge and indicative signs of
      depression among nursing students. Four instruments were used for data
      collection: A - Viewpoints on Depression; B - Knowledge on Depression; C - Beck's
      Inventory and D - Zung's Scale. The descriptive quantitative analysis added to
      qualitative reflections. Students showed that they were interested and that they
      had attended courses on mental health; 65.4% had high scores according to the
      expected viewpoints for depression; 61.5% showed excellent knowledge concerning
      depression. Two scales of depression showed moderate depression in one student.
      On basis of individuals responses, the students' lack of experience, some
      prejudice or erroneous information were observed.

PMID- 16419450
TI  - [Publications about nursing education in the Revista da Escola de Enfermagem da
      USP].
AB  - Scientific production in nursing education field provide important contributions
      to professional formation and nursing practice. Since we believe this
      perspective, we carried out a survey aimed at identifying and analyzing nursing
      education-related articles, building empiric categories from the collected data.
      This revision is a bibliographical, descriptive and quantitative survey using as
      source articles published in the Revista da Escola de Enfermagem da USP from 1967
      to 2002. We have found 1,137 articles, of which 14.2% refer to nursing education,
      89.0% of which are concerned with the undergraduate level. The descriptive
      analysis of nursing education-related bibliography gives rise to issues
      concerning the development of research that follow changes in the legislation
      changes and the demands of the professional market.

PMID- 16419451
TI  - [Assistance to the deaf in the health area as a factor of social inclusion].
AB  - The purposes of this article are to discuss the assistance to deaf people in the
      health area as a factor of social inclusion; to investigate with the deaf how the
      link with health workers is established; and to verify the deaf people's
      perception of the presence of sign language interpreters when they get health
      assistance. This is a descriptive and analytical survey with a qualitative
      approach carried out at a special school in Goiania. The sample was comprised of
      20 deaf students, and semi-structured interviews were used to collect the data.
      It was verified that the link is established when health workers are able to
      communicate with the deaf. The inclusion of the deaf in the health services is an
      evidence of difficulties in communication. It was concluded that the professional
      client relationship must be improved, that the link occurs when the client feels
      himself/ herself understood, and that the presence of an interpreter improves but
      is not enough to ensure the inclusion of the deaf.

PMID- 16419453
TI  - [Use of Travelbee's interpersonal relation process with mothers of newborns in a
      neonatal unit].
AB  - The objective of this study is to evaluate the interpersonal relation process
      with mothers of newborns in a neonatal unit using Joyce Travelbee's Interpersonal
      Relation Theory. It is a descriptive case study carried out in a neonatal
      internal unit in December of 2003 and January of 2004. Data were gathered through
      semi-structured interviews with person-to-person interaction. A questionnaire
      with six questions that showed the possibilities of reciprocal help in the face
      of the child's health problems was used. We also tried to soften the anguishes,
      doubts and fears through interaction with the mother. We verified that the use of
      the theory was relevant and served as a guide to help nurses perform a more
      ethical and human kind of care.

PMID- 16419452
TI  - [The critical patient and communication: the vision of the family regarding the
      nursing team].
AB  - Communication is considered an important variable in the care of critical
      patients and their families, whose difficulty concerning communication is
      expressed in the literature. The purpose of this survey was to verify what is
      considered adequate communication with the nursing team in the perception of the
      critical patient's family. This is an exploratory and field study carried out at
      the Intensive Care Unit of the University of Sao Paulo's Hospital Universitario.
      The population surveyed was comprised of 13 relatives of critical patients. The
      data was collected in November of 2003 and analyzed according to Bardin proposal.
      Communication was considered adequate when it was a means for information - the
      information was clear and objective, doubts were clarified, orientation was
      provided and communication was a form of humanizing health care - and there was
      verbal communication even when the patient was sedated, with somebody as a
      reference whom the relatives could resort to.

PMID- 16419454
TI  - [Participating in the construction of a teaching project for nursing].
AB  - The aim of the present paper is to report the authors' experience in the
      construction process of the teaching project for the Nursing Course at the
      Federal University of Sao Carlos. The study presents the course and the aspects
      related to the new proposal concerning the professional nurse profile, and the
      structure of the subjects distributed in modules are briefly reported. The
      collective construction and the difficulties regarding the curriculum
      reformulation process are placed in context. The integrated curriculum proposal
      should become effective in 2005, which will bring about the efforts of teachers
      in their search for the articulation of theory and practice without
      fragmentation. In order to succeed, the new teaching project will require efforts
      from teachers, students and the university administrative staff so that paths to
      overcome upcoming difficulties can be found.

PMID- 16419455
TI  - [Curriculum directions and strategies for the implementation of a new pedagogic
      proposal].
AB  - This study is aimed at contributing to the transformation movement to be
      developed in the Nursing Courses/Schools. The contribution refers to the
      formation of nurses with autonomy and discernment, to ensure the construction of
      the model of health attention, to the production of new knowledge and to the
      delivery of quality services directed to the health needs of the population. This
      study brings some conceptual and methodological reflections that may direct the
      change in the nurse formation process, as well as pointing strategies to
      implement the new pedagogic proposal from the challenge posed by the
      implementation of the National Curriculum Directions for Undergraduate Nursing
      Courses.

PMID- 16419456
TI  - [Gender equality and women's health].
AB  - Two stories are told: one that took place in the Middle Ages in Florence, Italy,
      the other in the 90s in Rio de Janeiro, Brazil. Both refer to the principle of
      Justice, the ethical pillar of Equality. From them is developed a gender analysis
      of the women's health situation and how much it reflects the iniquities that
      result from the conditions of social inequality to which they are subjected. The
      conclusion is that the adoption of gender equality as an ethical concept
      associated with the principles of social justice and human rights means to look
      over the daily life of thousands of women, to be indignant with the suffering and
      to bring about transformation, without mixing the right for dignified and
      respectable assistance because they are being, before anything, citizens, with
      the need to be healthy and productive, for being generators and maintainers of
      the present and future work force, of whom society depends for generating social
      wealth.

PMID- 16419457
TI  - [Fundaments for managing process in care practices].
AB  - A reflection on the elements that structure the process of the nurse's work with
      health and his/ her action. The study deals with health work, technologies in
      health and the management of care as pillars that serve as bases for the
      reflection, with the aim of helping the enlargement of the visibility of the
      nurse's acts. The importance of those fundaments for the exercise of care
      practices in the managing processes is highlighted.

PMID- 16419458
TI  - [Children with cancer and their families].
AB  - This study is aimed at reviewing the existing literature about children with
      cancer and their families in order to identify themes that have been researched
      and to survey indicators of need, thus giving subsidies for the systematization
      of nursing care. Systemized data collection was carried out in computerized
      databases between 1997 and 2002 using the keywords child, cancer, chronic
      illness/disease, family and nursing. A non-systemized research of scientific
      publications was also carried out. Results are grouped in three themes: impact of
      the child's cancer on the family system; adaptation process and coping strategies
      used by the parents in the face of the illness; and the process of loss and
      mourning in view of the child's death. The review demonstrated that nursing is
      constructing specific knowledge about the individual, cultural and regional needs
      of families of children with cancer, with a view to a nursing assistance that
      considers care in accordance to the singularity of each case.

PMID- 16419459
TI  - [Prognostic factor in gallbladder cancer].
AB  - BACKGROUND: Gallbladder cancer is a rare and aggressive neoplasm. OBJECTIVE: The
      purpose of this manuscript was to evaluate the prognostic factors associated with
      overall survival in gallbladder cancer patients. METHODS: We performed a
      retrospective study of the patients with gallbladder cancer who received
      attention in a tertiary referral center in Mexico City during a 13 year period
      (1990-2002). We evaluated demographic, clinical, pathological and treatment
      variables. The main outcome variable was overall survival. The survival curves
      were constructed with the Kaplan and Meier method and compared with the log-rank
      test. Multivariate analyses was performed with the Cox regression method. We
      considered significant p < 0.05. RESULTS: Fifty-one patients were registered, 35
      of them women (69%). Median patient age was 63 years. Fifty-seven percent of
      patients had previous diagnosis of cholelithiasis. Seventy-one percent of
      patients underwent surgery. Ninety-eight percent of the tumors were
      adenocarcinoma and 25% were poorly differentiated. Eighty-six percent were found
      to have stage IV. Median survival for the entire cohort was six months (95% CI
      0.5-7), and actuarial survival at one and three years was 22.7% and 3.9%
      respectively. On univariate analysis surgery, early stage, chemotherapy,
      Karnofsky 2 80 and serum albumin > 3.0 g/dL were associated with better
      prognosis. On multivariate analysis, only surgery (p = 0.0001) and serum albumin
      > 3 g/dL (p = 0.002) remained significantly associated with better outcome.
      CONCLUSIONS: Most cases of gallbladder cancer presented with advanced stage.
      Serum albumin is a prognostic factor for survival in this group of patients.

PMID- 16419460
TI  - Endoscopic retrograde cholangiopancreatography in the elderly.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a widely
      used technique for the diagnosis and treatment of biliary and pancreatic
      diseases. OBJECTIVE: To know the complication rate of ERCP in the elderly.
      PATIENTS AND METHODS: Patient files who underwent ERCP were reviewed and were
      divided into two groups: aged 65 and older (group 1) and less than 65 years
      (group 2). Socio-demographic variables, prophylactic antibiotic use, indications
      for ERCP and outcomes were assessed. RESULTS: Mean age in group 1 was 72.9 years
      and 41.7 years in group 2. Group 1 had more comorbidity (p < 0.001). The most
      frequent indication for the procedure was obstructive jaundice in both groups
      (63% versus 44%; p = 0.002). Malignancy was more frequent as a cause of biliary
      obstruction in group 1 (45% versus 21%; p < 0.001). ERCP was performed once in
      76% in group 1 and 93% in group 2 (p = 0.001). Prophylactic antibiotics were used
      more frequently in group 1 (84% versus 60%; p < 0.001). There were no differences
      between groups regarding infectious complications (p = 0.700). There was no
      difference in mortality rates between groups. CONCLUSION: ERCP is a safe
      procedure in elderly patients. The elderly frequently have more comorbidity.
      Nevertheless, the complication and mortality rates did not differ in this study.
      It is noteworthy that elderly patients received prophylactic antibiotics more
      frequently than younger patients but infectious complications were not different.
      The patients should not be excluded from ERCP based on their age.

PMID- 16419461
TI  - [Growth hormone and prolactin in maternal plasma and amniotic fluid during normal
      gestation].
AB  - OBJECTIVE: To measure the concentration of human growth hormone (GH) and
      prolactin (PRL) in maternal plasma (MP) and amniotic fluid (AF) during gestation
      and to evaluate their correlation. METHODS: HC and PRL were measured by
      radioimmunoassay in 60 healthy women with uncomplicated singleton pregnancies at
      16-36 weeks of gestation (WG). Trends of both hormones were estimated throughout
      pregnancy. The correlation of either hormone measured in different fluids was
      also estimated. RESULTS: GH in AF (AFGH) decreased significantly throughout
      pregnancy; (AF-GH = 21.32 - 0.54 X WG, r = -0.72 [95% confidence intervals (95%
      CI) -0.57-0.82], p = 0.001), and increased in MP (MP-GH); (MP-GH = 2.73 + 0.11 X
      WG, r = 0.45 [95% CI, 0.21-0.63] p = 0.05). The correlation between MP-GH and AF
      GH was, (AF-GH = 16.28 - 1.54 x - M-PGH, r = -0.47 [95% CI, -0.64 -0.21]; p =
      0.01). PRL values did not show significant differences neither in AF (AF-PRL /
      WG, r = 0.06, p = 0.6) nor in MP (MP-PRL / WG, r = 0.25, p = 0.14) during
      pregnancy, being AF-PRL (mean 151.3 ng/mL, SD 34.2 ng/mL) significantly higher
      than MP-PRL (mean 119.3 ng/mL, SD 55.4 ng/mL) (p = 0.006) in all the studied
      period. CONCLUSION: AF-GH and MP-GH showed a significant negative correlation
      during pregnancy. PRL measured in AF and PM did not show changes throughout
      gestation being AF-PRL significantly higher than MP-PRL.

PMID- 16419462
TI  - [Factors related to subjective evaluation of quality of life of diabetic
      patients].
AB  - OBJECTIVE: To determine the relationship between some clinical and psychosocial
      factors and the quality of life of a group of diabetic patients. METHOD: A cross
      sectional study was done with diabetic patients attending a primary care unit.
      Quality of life was evaluated with a verbal global scale. The clinical and
      psychosocial factors studied were: type of diabetes, duration of the disease,
      type of treatment, associated diseases, complications, metabolic control
      (glycosylated hemoglobin), treatment compliance, coping styles, negative attitude
      to disease, social support, and socioeconomical level. RESULTS: We interviewed
      173 patients, most women (739%), most type 2 (95%). We found that being a woman
      was a factor negatively related to quality of life. Of clinical variables, only
      duration of disease was slightly correlated with quality of life (-0.14).
      Psychological and social variables were significantly correlated with quality of
      life. We performed a stepwise multiple regression analysis and we found that
      seven psychosocial variables explained 30% of variance of quality of life.
      CONCLUSIONS: Our results indicate that clinical factors did not correlate with
      quality of life. It is the way the patient lives with diabetes and not the
      diabetes by itself what affects the quality of life of diabetic patients. Some
      psychological and social variables were significantly related to quality of life
      of these patients.

PMID- 16419463
TI  - [Clinical aptitude of family doctors in the management of patients with diabetes
      type two with initial nephropathy].
AB  - The diabetic nephropathy in initial phase requires an opportune identification by
      family physicians. Indeed, they should be qualified to interpret the data that
      suggesting that a patient be going through that phase of the illness, in order to
      orientate the management and processing of the same one, from an integrative
      perspective. The purpose of this work was to measure the aptitude of the family
      doctors to interpret, to judge and to propose in front of sick patients with
      diabetes type two with initial nephropathy. We made this with a representative
      sample of family physicians in five Family Medicine Units of the Instituto
      Mexicano del Seguro Social in the city of Guadalajara, Jalisco, Mexico. The main
      variable of the study was the clinical aptitude of the doctors: interpretation,
      judgment and proposals carried out in the practice of their profession; and
      through an ordinal scale, levels of aptitude' were defined, which related to the
      remainder of variables using the medium, Kruskal Wallis stadiometer and chi2.

PMID- 16419464
TI  - [Anthropometrical measurements as predictor of serum lipid profile in adolescents
      with Down syndrome].
AB  - Current findings suggest that more attention needs to be given to the increase in
      body mass being achieved by disabled populations in general and individuals with
      mental retardation in particular, to minimize long-term negative health
      consequences. Given that physical activity programs have been reported as one of
      the most effective ways of improving the health of individuals with Down
      syndrome, it would be of interest facilitate different tools to contribute to
      their clinical follow-up. Consequently, this study was designed to assess the
      correlation between anthropometrical parameters and lipid profile in adolescents
      with Down syndrome. Anthropometric variables such as body mass index, waist
      circumference and waist-to-hip ratio as well as serum lipids (total cholesterol,
      high-density-lipoprotein cholesterol, total-cholesterol/high-density-lipoprotein
      cholesterol and triglycerides) were measured in 21 male adolescents (16.3 +/- 1.1
      years) with Down syndrome. Anthropometric parameters presented a positive
      association with serum lipids except for high-density-lipoprotein cholesterol
      that was negative. It should be emphasized the strongest association of waist-to
      hip ratio to total cholesterol/high-density-lipoprotein cholesterol ratio (r =
      0.48; p < 0.05). It is concluded waist circumference and waist-to-hip ratio may
      be highly recommended in clinical practice as appropriate anthropometric
      predictors of lipid profile in adolescents with Down syndrome. Further studies
      are required to assess their behavior during physical activity programs as well
      as to determine more correlations in these individuals.

PMID- 16419466
TI  - [Secondary peritonitis].

PMID- 16419465
TI  - [Bioterrorism agents: getting ready for the unthinkable].
AB  - The September 11, 2001 terrorist attacks in the U.S.A. demonstrated our
      vulnerability to terrorist raids. Furthermore, in the same year inhalational
      anthrax cases in humans caused by the intentional [corrected] release of Bacillus
      anthracis spores via the U.S.A. postal system inflicted a lot of panic and terror
      over the civilian population. The succeeding terrorist events scattered in
      several other countries are continuous reminders of our frailness [corrected] and
      of the risk that terrorists attempts in the future may be implemented by means of
      deliberate evil release of biological agents. These events may be perpetrated by
      either the release of an infectious agent or any of its products in order to
      spread death or sickness in humans, animals, or plants with the obnoxius purpose
      of scaring governments and societies for the profit of particular ideological
      causes. In the current article, we present a review of the main bioterrorism
      agents, as well as a historical and clinical aspects and their significance for
      public health preparedness and response.

PMID- 16419467
TI  - [Effect of biotin upon gene expression and metabolism].
AB  - During the last few decades, an increasing number of vitamin-mediated effects has
      been discovered at the level of gene expression in addition to their well-known
      roles as substrates and cofactors; the best recognized examples are the
      lipophilic vitamins A and D. Although little is known about water-soluble
      vitamins as genetic modulators, there are increasing examples of their effect on
      gene expression. Biotin is a hydro soluble vitamin that acts as a prosthetic
      group of carboxylases. Besides its role as carboxylase cofactor, biotin affects
      several systemic functions such as development, immunity and metabolism. In
      recent years, significant progress has been made in the identification of genes
      that are affected by biotin at the transcriptional and post-transcriptional
      levels as well as in the elucidation of mechanisms that mediate the effects of
      biotin on the gene expression. These studies bring new insights into biotin
      mediated gene expression and will lead to a better under-standing of biotin roles
      in the metabolism and in systemic functions.

PMID- 16419468
TI  - [Bioethical reflections: necessity to promote altruistic attitudes toward medical
      research in human beings].
AB  - In this paper some bioethical reflections about medical research in human beings
      are made. The social moral obligation to increase this kind of investigation,
      with the purpose of enlarging resources to take care of the health of society, as
      well as to comply with the moral duty of keeping the integrity of the
      participating subjects, have placed to medical investigators face to face with
      ethical problems that may affect the development of this essential activity for
      human healthcare. On one hand, in the present context, the resistance of both
      healthy and sick individuals to collaborate in the studies, as possible,
      according to a wrong autonomous decision (irreflexive individualism). On the
      other hand, the shortage of anticipating strategies that promotes altruistic
      attitudes to take into account, the suffering experiences proper of human nature.
      In this regard, the author focuses his reflections, from the principle of social
      welfare that underlies medical research and of the necessity of providing
      instrumentation for some educational policy that without lacking respect for the
      autonomy of subjects, would propitiate the participation of society so that
      humanity would continue to benefit from the achievements of this type of
      research.

PMID- 16419469
TI  - [Recommendations for the medical treatment of rheumatoid arthritis].

PMID- 16419470
TI  - [The role of preserving therapy of invasive cancer of the urinary bladder].
AB  - Cystectomy in the treatment of invasive cancer of the urinary bladder is not the
      only therapeutic modality in this pathology. In selected patients an alternative
      exists--transurethral resection of the urinary bladder followed by adjuvant
      concurrent chemotherapy and radiotherapy. The preserving therapy can be
      recommended to patients over 60 years of age in the presence of a low-grade
      solitary tumor of a mobile wall of the urinary bladder respectable with
      preservation of the organ capacity.

PMID- 16419471
TI  - [Subtotal transurethral prostatectomy in the treatment of patients with prostatic
      cancer].
AB  - The results are given of subtotal transurethral resection (subtotal TUR) in 21
      patients with prostatic cancer (PC) operated in 1998-2004. The patients had
      contraindications to radical treatment. The aim of the surgical intervention was
      maximal possible removal of the prostatic tissue to the prostatic capsule that
      improves results of adjuvant hormonal and radiotherapy. Postoperative follow-up
      lasted from 6 months to 6 years. The control groups consisted of 20 patients
      subjected to palliative prostatic TUR and 24 PC patients given only hormonal or
      radiotherapy. Subtotal transurethral prostatectomy and TUR of the prostate were
      successfully made in all the patients. The number of postoperative complications
      and reoperations was less in patients after subtotal transurethral prostatectomy
      than in those after palliative TUR. The treatment reduced blood PSA levels in all
      the groups but the progress of this reduction depended on the treatment method.
      The group after subtotal transurethral prostatectomy achieved maximal PSA
      lowering after 2 months after surgery. The follow-up registered distant
      metastases in 19.04% patients of the study group and 20 and 29.4% in the control
      groups. One-year survival was 80.95, 80, 83.3%, respectively; 3-year survival was
      80, 45.5 and 77.8%, respectively. Thus, combined treatment of prostatic cancer
      (subtotal transurethral prostatectomy and maximal androgenic blockade) rapidly
      corrects urination without deterioration of survival parameters compared to
      hormonal therapy alone.

PMID- 16419472
TI  - [Prognostication of 5-year survival in patients after radical prostatectomy].

PMID- 16419473
TI  - [Effects of parallel ultrasonic visualization of the prostate in sagittal and
      cross projections in transrectal biopsy on detectability of prostatic cancer].
AB  - The results of 526 transrectal prostatic biopsies are available. Mean age of the
      patients was 64.6 years, mean level of PSA--10.4 ng/ml, mean size of the prostate
      -56 cm3. Biopsy was made in visualization of the prostate in the sagittal
      projection (ultrasound devices Bruel & Kjaer 1846 and Kretz Voluson 730).
      Application of Bruel & Kjaer Medical 2102 Hawk provides visualization of the
      prostate during biopsy both in sagittal and cross projection. Double
      visualization significantly improved detectability of prostatic cancer in
      patients with PSA 4-10 ng/ml. In biopsy of the top and peripheral zone there was
      lengthening of prostatic tissue fragments, reduced fragmentation of the columns,
      less frequent blank shots of the biopsy gun. The data obtained supports the
      importance of isolated placement and marking of prostatic tissue fragments in
      biopsy and allow to recommend wide clinical use of ultrasonic facilities with
      biplanic sensors providing online sagittal and cross visualization of the
      prostate.

PMID- 16419474
TI  - [Changes in prostatic circulation in response to laser therapy and magnetic
      therapy in patients with benign prostatic hyperplasia].
AB  - The results of preoperative preparation were analysed in 59 patients with
      prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were
      assessed by transrectal ultrasound (color Doppler mapping) in two groups of
      patients. Group 1 received combined therapy including transrectal laser radiation
      of the prostate, group 2--transrectal magnetotherapy. The analysis showed that
      laser radiation reduced insignificantly the size of the prostate and adenomatous
      node, improved microcirculation and circulation in the prostate. This resulted in
      relief of inflammation and reduction of the number of postoperative inflammatory
      complications. Transrectal magnetotherapy has a positive effect on
      vascularization and hemodynamics of the prostate, local immunity, contamination
      of the tissues with pathogenic flora.

PMID- 16419475
TI  - [Chemical destruction of the prostate by Prostalyser-1 and Prostalyser-2
      solutions: an experimental study in dogs].
AB  - The aim of the study was elaboration of a new minimally invasive but effective
      alternative method of BPH treatment. The experiments were carried out on 46 male
      dogs divided into two equal groups. 10 ml of Prostalyser-1 solution (natrii
      chloridi 9.5 g, dimethylsulfoxidi 0.5 g, aquae destill. Ad 1000.0 g) was given in
      a single injection into the prostates of the first group of animals. The same
      volume of Prostalyser-2 solution (spiritus ethilicus 96% - 76.5 g, DMSO 0.5 g,
      aq.destill ad 100.0 g)--into the prostates of the other group, respectively. The
      temperature of the solutions was +80 degrees C. Within the first 2 months,
      essential disorders were observed in the cellular Na-pump, membrane permeability
      system, there were lobular and diffusive necroses in prostatic alveolar
      epithelium and a decrease of the prostate weight by 68-66%. This condition of the
      prostate persisted for 4-6 months. Prostalyser-1 and Prostalyser-2 solutions can
      be recommended as very prospective substances for chemical destruction of the
      prostate in case of BPH.

PMID- 16419476
TI  - [An original modification of wedge resection of the kidney in renal cell
      carcinoma].
AB  - Organ-preserving surgery was made in 133 patients with renal cell carcinoma. An
      original modification of renal resection with administration of the drug
      tachocomb was conducted in 22 patients. Short- and long-term surgical outcomes
      demonstrate advantages of the surgery supported by the results of postoperative
      monitoring including ultrasound angiography, computed and magnetic resonance
      imaging.

PMID- 16419477
TI  - [Choice of corporoplastic method in Peyronie's disease depending on hemodynamic
      status of the penis].
AB  - We studied 164 patients with Peyronie's disease, 34 of whom have clinical
      symptoms of erectile dysfunction. Dopplerography has detected alterations of
      penile hemodynamics in 71.8% cases. Vein occlusive dysfunction prevailed (54.8%).
      Dopplerographic signs of venoocclusive dysfunction were seen also in patients
      with minor erectile disorders (55.4%). The analysis of absolute values of the
      systolic velocity peak allowed us to consider values in the range > 25 but < 35
      cm/s as borderline or suboptimal, corresponding to subclinical period of
      venoocclusive dysfunction. Dynamic cavernosometry results served the basis for
      criteria of subclinical venoocclusive dysfunction characterized by threshold
      intracavernous pressure 50 mm Hg, coefficient of 30-s reduction of intracavernous
      pressure from 1.75 +/- 0.93 to 2.1 +/- 0.8 mm Hg and supporting perfusion
      velocities under 29.2 +/- 15 ml/min. Characteristics of hemodynamic status and
      penile geometry help an optimal choice of deviation correction in patients with
      Peyronie's disease.

PMID- 16419478
TI  - [The role of nitric oxide in fertility disorders in men].
AB  - The aim of the study was investigation of NO influence on fertility properties of
      ejaculate in the diseases of male sex organs. A total of 73 males aged 20-55
      years with different sexual disorders were examined. Potentiometric assay for
      nitrates in ejaculate, size and shape of spermatosoa were studied. NO3 was
      present in all sperma samples. In the control group nitrates levels were 0.662 +/
      0.147 mmol/l. In men with sexual diseases nitrates levels in ejaculate ranged
      from 0.114 mmol/l to 1.530 mmol/l). In normozoospermia nitrates occurred in
      "mean" levels (0.295 mmol/l to 0.900 mmol/ 1). In pathospermia nitrates level was
      high. NO produces a protective action if it was in adequate quantity.
      Spermatozoid concentration and a relative number of progressive-mobile forms
      correlated negatively with nitrates of spermatic plasma (r = -0.40) while dead
      spermatozoa percentage correlated positively. Thus, low NO3 content in ejaculate
      may result from microcirculatory disorders and endothelial dysfunction in
      testicular parenchyma and epididimus. NO hyperproduction occurs in inflammatory
      urogenital diseases. It probably induces pathospermia via direct toxic effects of
      NO and stimulation of lipid peroxidation.

PMID- 16419480
TI  - [Diagnosis of endogenic intoxication in children with acute and chronic renal
      failure].

PMID- 16419479
TI  - [Doppler technologies in combined diagnosis of acute pyelonephritis].
AB  - We studied diagnostic potentialities of conventional clinical, device, x-ray and
      ultrasonic methods including current Doppler technology in differentiation of
      serous and purulent stages of acute pyelonephritis (AP) in 50 patients (mean age
      25.5 +/- 5.5 years). Energetic dopplerangiography (EDA) showed the highest
      diagnostic significance. EDA was highly informative in renal carbuncle and total
      purulent destruction of the kidney and low informative in serous and apostematous
      AP, renal abscess. Conventional ultrasonic, x-ray, clinical and device
      investigations as well as impulse dopplerography and color Doppler mapping of
      blood flow are of secondary importance in AP.

PMID- 16419481
TI  - [Bacteriophages use in the treatment of pyoseptic complications in a female
      patient with renal allotransplant].

PMID- 16419482
TI  - [True serous extraorganic retroperitoneal cyst].

PMID- 16419483
TI  - [Spontaneous rupture of the kidney in a patient with renal hemangioma and
      nephrogenic hypertension].

PMID- 16419484
TI  - [Endoprosthetic operation of the solitary kidney ureter in Burneville-Pringle
      disease complicated with hydronephrosis].

PMID- 16419486
TI  - [Surgical treatment of urogenital anomalies in males].

PMID- 16419485
TI  - [Current methods of surgical treatment of children with urolithiasis].

PMID- 16419487
TI  - Diabetic dyslipidemia and response to intensified glycemic treatment: why there
      are differences?

PMID- 16419488
TI  - Role of candidate genes in the lipid responses to intensified treatment in Type 2
      diabetes.
AB  - OBJECTIVE: To identify genetic factors related to individual differences in lipid
      responses to intensified treatment in Type 2 diabetes. DESIGN AND METHODS: After
      evaluation and intensification of their treatment, 107 Type 2 diabetes patients
      with poor metabolic control were re-evaluated after mean follow-up time of 15.6
      (0, 4) (SE) months. The genes coding major lipid regulatory proteins and their
      relations to plasma lipid and lipoprotein changes were studied. RESULTS: During
      the follow-up, levels of glycohemoglobin A1 (GHBA1) decreased (-1.7%), plasma HDL
      cholesterol (+0.05 mmol/l) and lipoprotein (a) [Lp(a)] (+4.2 mg/dl) increased,
      while triglyceride (TG) levels decreased (-1.2mmol/l) despite mean weight gain of
      2.1 kg (p from <0.01 to <0.001). Of the gene markers studied, the lipoprotein
      lipase (LPL) Pvull (p=0.005) independently affected changes in HDL-cholesterol
      and was associated with the frequency of coronary heart disease (CHD). Lp(a)
      changes were associated with apolipoprotein B (ApoB) Glu4154Lys polymorphism
      (p=0.004). CONCLUSIONS: These results suggest that genetic variations at LPL and
      ApoB loci are among the factors contributing to the variability in response to
      lipid parameters to therapy in Type 2 diabetes. LPL Pvull rare allele homozygote
      status seems to be beneficial with more favorable lipid changes and protection
      against CHD.

PMID- 16419489
TI  - High iodine intake is a risk factor of post-partum thyroiditis: result of a
      survey from Shenyang, China.
AB  - The aim of the present study is to obtain the epidemiological data on post-partum
      thyroiditis (PPT) firstly in Chinese women, and to tryto evaluate whether
      excessive intake of iodine in post-partum women imposes any danger of occurring
      PPT. Sixty hundred and ten pregnant women were involved in the cohort just before
      delivery. Four hundred and eighty-eight (80%) of them accepted taking part in
      follow-ups more than 6 months post-partum. A blood sample was taken from
      participants before delivery and every 3 months post-partum for testing of serum
      TSH, thyroid autoantibodies. Free T3 (FT3), free T4 (FT4) and TSH receptor
      antibody (TRAb) were detected if TSH was abnormal. The iodine nutrition was
      evaluated according to the mean level of the fasting urinary iodine excretions at
      different times during the studying period, and participants were subgrouped into
      3 categories with low, adequate and high iodine intake. For those participants
      who had thyroid dysfunction within 6 months post-partum, the follow-up persisted
      for 1 yr. Of 488 pregnant women, PPT developed in 11.9% (58/488). Given overt and
      subclinical PPT, the prevalence was 7.17% (no.=35) and 4.71% (no.=23),
      respectively. There was a strong association between the presence of thyroid
      peroxidase antibody (TPOAb) at delivery and the risk of developing PPT [RR=6.76,
      95% (CI) 4.42-10.34]. Overt cases had much higher titers of TPOAb than
      subclinical patients (all p<0.05). The median urinary iodine (MUI) of patients
      with PPT was significantly higher than that of healthy women (231.93 vs 199.88
      microg/l p=0.00153). Both the prevalence of PPT and positive TPOAb rise with the
      increment of iodine intakes. Pregnant women with high iodine intake had more risk
      of developing PPT when compared with those with low iodine intake (RR=2.92, 95%CI
      1.31-6.50). We concluded that positive TPOAb was of value for predicting the
      occurrence and severity of PPT, and a high iodine intake was a risk factor
      triggering PPT.

PMID- 16419491
TI  - Influence of subclinical hypothyroidism and T4 treatment on the prevalence and
      severity of obstructive sleep apnoea syndrome (OSAS).
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) and subclinical hypothyroidism are
      relatively frequent disorders that may be causally linked. However, discordant
      results exist on the prevalence and severity of OSA in subclinical
      hypothyroidism. The aim of this study was to compare the prevalence and severity
      of sleep-disordered breathing in individuals with or without subclinical
      hypothyroidism, and to investigate the possible effect of levothyroxine treatment
      on these patients. PATIENTS AND METHODS: One hundred and eight subjects were
      consecutively enrolled and divided in 3 groups, according to the TSH levels and
      levothyroxine therapy. The first group (Group A) was represented by 63 subjects
      with normal TSH and thyroid function. The other two groups included patients
      affected by subclinical hypothyroidism; one group (Group B) treated with
      levothyroxine, while the other group (Group C) was never treated with
      levothyroxine. Anthropometric, respiratory and polysomnographic data were
      evaluated in all individuals. RESULTS: The percentage of OSA, neck circumference,
      and body mass index (BMI) were not statistically different among the 3 groups.
      Respiratory disturbance index (RDI) as well as the percentage of the total number
      of events (apnoea-hypopnoea) by total sleep time (TST) with <90% oxyhemoglobin
      saturation (TSTSaO2 <90%) were not different among the groups. When we observed
      OSA patients, the only significant difference between groups B and C was
      represented by the Epworth Sleepiness Scale (ESS) (p=0.005). CONCLUSION: This
      study shows that subclinical hypothyroidism and treatment with levothyroxine do
      not influence the prevalence and severity of OSA, while sleep propensity is
      increased by untreated subclinical hypothyroidism.

PMID- 16419490
TI  - Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary
      syndrome.
AB  - OBJECTIVE: Neuroendocrine dysfunction in polycystic ovary syndrome (PCOS) was
      addressed by studying the steroid hormone changes in women with PCOS with either
      high or normal LH levels leading to inferences regarding the primacy of elevated
      LH in the pathophysiology of PCOS. METHODS: A cross-sectional study was designed
      in an academic clinical facility involving 234 women with PCOS. Patients were
      divided into two groups based on an LH/FSH ratio < or >1 and hormonal and
      metabolic studies were performed in both groups. Factors were determined by
      binomial logistic regression that predicted group membership of these women.
      RESULTS: Higher follicular phase estradiol (E2) and androstenedione (A4) levels
      as well as greater insulin sensitivity were the only factors that predicted the
      presence of neuroendocrine dysfunction with elevated A4 being necessary for
      neuroendocrine dysfunction. CONCLUSIONS: It was concluded that uncoupling of
      hypothalamic E2 inhibition by elevated ovarian A4 associated with E2 related
      sensitization of pituitary LH leads to neuroendocrine dysfunction in PCOS.

PMID- 16419492
TI  - Peroxisome proliferator-activated receptor (PPAR)gamma is highly expressed in
      normal human pituitary gland.
AB  - OBJECTIVE: Expression of peroxisome proliferator-activated receptor (PPAR)gamma
      in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of
      the study was to evaluate the expression of PPARgamma in normal human pituitary
      tissue and to study its localization in the pituitary secreting cells. MATERIALS
      AND METHODS: Normal pituitary tissue samples were obtained form 11 patients with
      non-secreting adenoma who underwent surgical excision of the tumor. Expression of
      PPARgamma was evaluated by immunostaining and western blotting; localization of
      PPARgamma in each pituitary secreting cell lineage was evaluated by double
      immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas
      served as Controls. RESULTS: PPARgamma was highly expressed in all pituitary
      samples with a (mean +/- SD) 81 +/- 6.5% of stained cells; expression of
      PPARgamma was confirmed by western blotting. Non-functioning pituitary adenomas
      had 74 +/- 11% PPARgamma positive cells. Expression of PPARy was either in
      cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARgamma ligand
      was associated with traslocation of the receptor from cytoplasm into the nucleus.
      Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH,
      FSH, PRL and ACTH) had PPARgamma expressed. DISCUSSION: The present study
      demonstrated that PPARgamma is highly expressed in every normal pituitary
      secreting cell lineage. It can translocate into the nucleus by ligand binding;
      however, its role in pituitary hormone regulation remains to be elucidated.

PMID- 16419493
TI  - Exon 5 of the RET proto-oncogene: a newly detected risk exon for familial
      medullary thyroid carcinoma, a novel germ-line mutation Gly321Arg.
AB  - Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited
      disease, characterized by germ-line mutations in the RET proto-oncogene, mainly
      in exons 10 and 11, but also in exons 13, 14 and 15. Recently, mutations in exons
      8 and 16 associated with FMTC were also described. In the herein presented study,
      single strand conformation polymorphism (SSCP) method for rapid screening of
      mutations in the RET proto-oncogene and fluorescent sequencing method were used.
      In one Czech family with FMTC, we have identified a novel missense point mutation
      of the RET proto-oncogene in exon 5, that results in substitution of arginine by
      glycine at codon 321 in the cadherin-like domain of ret protein. It seems that
      this mutation causes FMTC as no other mutation was found in the classical risk
      exons (10, 11, 13, 14, 15 and 16) of the RET proto-oncogene. The mutation
      cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH)
      in two patients; two other family members are mutation carriers without clinical
      signs of MTC so far. To improve the diagnosis of FMTC, analysis of exon 5 of the
      RET proto-oncogene should be considered in families with no identified classical
      RET mutations.

PMID- 16419494
TI  - The role of non-calcemic analogs of vitamin D in differentiation of cultured rat
      bone marrow into osteoblast-like cells: age and sex differences.
AB  - We have previously demonstrated that rat bone in vivo and rat bone cells in
      vitro, responded sex-specifically to gonadal steroids in stimulation of the
      specific activity of the BB isozyme of creatine kinase (CK), a marker for
      hormonal responsiveness. Pre-treatment with vitamin D analogs up-regulated the
      sex-specific responsiveness and sensitivity to gonadal steroids. We also found
      that mice cultured femoral bone marrow (BM) in the presence of dexamethasone
      (DEX) and 1,25(OH)2D3 (1,25D) or both differentiated into osteoblast-like cells
      (Obs), which acquired sex-specific responsiveness to gonadal steroids. This
      response was significantly augmented in the presence of both agents. In the
      present study, we examined the effect of age, sex and vitamin D non-hypercalcemic
      analogs on the differentiation of rat derived femoral BM into Obs. In female or
      male derived BM from intact but not gonadectomized rats DEX and DEX+1,25D
      increased the constitutive levels of CK. BM derived from old females showed lower
      stimulation of CK than BM originated from young females by estradiol (E2) or
      raloxifene (Ral) in the presence of both DEX and 1,25D. The non-hypercalcemic
      analogs of vitamin D: CB 1093 (CB), EB 1089 (EB) and MC 1288 (MC) were more
      effective than 1,25D in both age groups in stimulating CK in the absence of DEX.
      In the presence of DEX, there was a further increase in CK with the same
      differential effectiveness. BM from gonadectomized male or female rats lost the
      sex-specific response, responding to both E2 and dihydrotestosterone (DHT). BM
      derived from both intact and gonadectomized males and females, growing with DEX
      or DEX+1,25D showed increased specific activity of constitutive levels of
      alkaline phodphatase (AP). No significant stimulation of AP was seen in any BM by
      gonadal steroids. These findings suggest that manipulation of the hormonal milieu
      in early stages of differentiation sequence of Obs determines the subsequent
      selective responsiveness of the developing bone tissue to sex steroids. Also non
      calcemic vitamin D analogs were more effective in this process than 1,25D and
      showed activity even in the absence of DEX and may be applied to the
      differentiation process for bone tissue engineering.

PMID- 16419495
TI  - Long-term culture in dexamethasone unmasks an abnormal phenotype in osteoblasts
      isolated from osteoporotic subjects.
AB  - We have shown that osteoblastic cells derived from trabecular bone explants of
      osteoporotic subjects (OP cells) exhibited an altered alkaline phosphatase (ALP)
      response to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] compared to control (CON)
      cells. Our hypothesis that OP cells have other intrinsic abnormalities was
      investigated using our cell models representing two different stages of
      differentiation. OP and CON cells were cultured in the absence (-DEX) or presence
      (+DEX) of 10 nM dexamethasone (DEX) in 10% fetal calf serum (FCS) prior to
      exposure to serum-free medium containing 1 nM of PTH and/or 17-beta estradiol
      (E2). Both OP and CON cells responded to DEX with a two-fold increase in basal
      ALP activity. While E2 or PTH+E2 had no effect on OP cells, both treatments
      inhibited ALP activity in CON cells (p<0.05). OP and CON cells grown in DEX also
      expressed PTH-stimulated adenylate cyclase (AC) activities higher than those of (
      DEX) cells. OP+DEX cells, however, exhibited activities which were 8-fold higher
      than those of CON+DEX cells (p<0.001). In OP+DEX cells, E2 stimulated basal AC
      activity (p<0.05) but did not affect PTH-stimulated activity. In contrast, in
      CON+DEX cells, E2 had no effect on basal activity but inhibited PTH-stimulated AC
      activity (p<0.001). Osteocalcin production was 4-fold lower in OP+DEX cells
      compared to OP-DEX and CON cells (p<0.05) while osteocalcin mRNA levels were
      significantly lower in OP+DEX and CON+/-DEX cells compared to OP-DEX cells
      (p<0.05). E2 did not affect osteocalcin protein or mRNA levels in either OP or
      CON cells. No differences in mRNA levels were found for estrogen receptor-alpha
      (ER-a) in OP+/-DEX cells whereas these levels were significantly higher in
      CON+DEX compared to CON-DEX cells (p<0.05). These results indicate that DEX
      amplified the differences between OP and CON cells and confirm the presence of
      intrinsic osteoblastic abnormalities in patients with osteoporosis that persist
      in culture.

PMID- 16419496
TI  - Plasma total homocysteine level and its association with carotid intima-media
      thickness in obesity.
AB  - BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) and
      obesity are risk factors for cardiovascular disease. The relationship between
      hyperhomocysteinemia and obesity has not been totally elucidated. OBJECTIVE: The
      first aim of the study was to investigate whether anthropometric measurements and
      insulin resistance contribute to the variation in homocysteine levels in obese
      adults. Our second aim was to determine if any relationship exists between the
      carotid intima-media thickness (IMT) and plasma tHcy levels in obese subjects
      without traditional cardiovascular risk factors. MATERIAL AND METHODS: Fifty-five
      obese (15 male, 40 female) and 30 (11 male, 19 female) age- and sex-matched
      apparently healthy volunteers were included. Exclusion criteria were smoking,
      hypertension, diabetes, vitamin ingestion, hyperlipidemia, renal failure, liver
      disease, pregnancy, menopause and secondary obesity such as Cushing's syndrome,
      hypothyroidism. tHcy, folate, vitamin B12 levels, fasting insulin, glucose, total
      cholesterol, triglycerides, HDL, LDL particles, uric acid, creatinine and
      creatinine clearance were measured. Non-invasive ultrasound measurements of
      carotid IMT were performed. RESULTS: tHcy levels and carotid IMT were comparable
      between obese and non-obese subjects. Waist/hip ratio (WHR) was related to tHcy
      and carotid IMT. Hyperhomocysteinemic subjects (tHcy >19.2 micromol/l) had
      greater WHR than normo-homocysteinemic subjects. Both tHcy levels and carotid IMT
      were higher in male subjects both in obese and non-obese subjects. No association
      was observed between insulin resistance and tHcy and carotid IMT. Renal function
      and abdominal obesity were significant predictors of plasma tHcy levels.
      CONCLUSIONS: We concluded that, in obese subjects who are free from
      atherosclerosis and impaired renal function, plasma tHcy levels do not differ
      from healthy subjects. Plasma tHcy concentrations are not related to carotid IMT
      in obese subjects during the non-atherogenic stage. Although no significant
      difference was observed between insulin-resistant and insulin-sensitive subjects
      compared to the plasma tHcy levels, the relationship between tHcy levels and some
      components of the insulin resistance syndrome may support the opinion that tHcy
      may be considered a component of the insulin resistance syndrome.

PMID- 16419498
TI  - Seizures as the only clinical manifestation of reactive hypoglycemia: a case
      report.
AB  - A 45-yr old diabetic patient, who had received a diagnosis of grand mal epilepsy,
      for two episodes of nocturnal tonic-clonic convulsions, underwent continuous
      glucose monitoring (CGM). During CGM, the patient had an episode of tonic-clonic
      convulsion, and at the same time a prolonged nocturnal hypoglycemia (<2.2 mmol/l)
      was observed. CGM revealed that tonic-clonic convulsions, which had been
      interpreted as a manifestation of epilepsy, were in fact a symptom of severe
      hypoglycemia. In order to assess the pathogenesis of hypoglycemia, the patient
      underwent a 75-g oral glucose tolerance test, that was interrupted shortly
      afterwards for hypoglycemic symptoms (i.e., reactive hypoglycemia). To our
      knowledge, this is the first case ever reported of reactive hypoglycemia
      associated with Type 2 diabetes.

PMID- 16419497
TI  - Idiopathic hypogonadotrophic hypogonadism associated with arachnoid cyst of the
      middle fossa and forebrain anomalies: presentation of an unusual case.
AB  - We report a 22-yr-old male patient with hypogonadotrophic hypogonadism (HH)
      associated with a giant middle fossa arachnoid cyst (AC) diagnosed by magnetic
      resonance imaging (MRI). He presented with pubertal and growth delay. He also had
      learning disabilities and anosmia. Laboratory investigation revealed pre-pubertal
      levels of testosterone and normal results of the combined test of anterior
      pituitary function, except for in GnRH acute and prolonged test. Cranial MRI
      showed an AC in left middle fossa with expansion to suprasellar cisterna and
      several abnormalities like left temporal lobe hypoplasia, left optic tract and
      bilateral olfactory bulb hypoplasia and left hypothalamic hypoplasia.

PMID- 16419499
TI  - Familial parathyroid hyperplasia: is there a place for minimally invasive
      surgery? Description of the first treated case.
AB  - While the majority of patients affected with sporadic primary hyperparathyroidism
      (sPHPT) can be selected for minimal access surgery, patients affected with 4
      gland hyperplasia still do not represent an indication for it. Minimally invasive
      video-assisted parathyroidectomy (MIVAP) was introduced in 1996; this technique
      relies on a single central incision and external retraction and therefore allows
      a bilateral neck exploration. This was the case of a 27-yr-old female with
      familial primary hyperparathyroidism (FPHPT). Three enlarged glands were
      immediately identified in orthotopic positions and the fourth was
      intrathyroideal. A subtotal parathyroidectomy was then performed, leaving a small
      fragment of the inferior right gland and completed with the cervical thymectomy
      by inverting the positions of the camera and the retractor assistants with regard
      to the positions originally described. Quick intraoperative PTH assay (QPTH)
      confirmed the surgical cure of the disease.

PMID- 16419500
TI  - Historical milestones in endocrinology.
AB  - The 1865 volume of the "II Morgagni", one of the most important Italian medical
      journals of the 19th century, presented two important articles, milestones for
      further scientific studies in the field of sexual differentiation. One was the
      original description of the "ramified cells" of testicular tubules by E. Sertoli,
      known today as Sertoli cells. The other was the first report and description of a
      patient with ambiguous genitalia, huge hyperplastic adrenal glands and salt
      wasting symptoms: a true case of congenital adrenal hyperplasia, a disease well
      delineated only 80 yr later. Sertoli, although young (22 yr old) and
      inexperienced, was absolutely sure of his observation, also against the opinion
      of other important anatomists. He described different ways of presentation of
      these cells, hypothesized on their supportive and nutritive functions, but not on
      any endocrine function at that time. The second article was written by L. De
      Crecchio, a Professor of Forensic Medicine, and was the detailed description of
      the clinical, psychological and autoptic features of a female patient with severe
      ambiguous genitalia, who today would be diagnosed as having congenital adrenal
      hyperplasia probably due to 21-hydroxylase deficiency. This article gives, still
      today, important news on the clinical, psychological and social outcome of these
      patients before the possibility of therapy.

PMID- 16419502
TI  - [Why a special number about feet?].

PMID- 16419503
TI  - [Generalities about foot].

PMID- 16419504
TI  - [Factors influencing the architecture and the clinical aspects of the foot].

PMID- 16419501
TI  - Melanotrope cells as a model to understand the (patho)physiological regulation of
      hormone secretion.
AB  - Regulation of hormone secretion is a complex process that comprises the
      sequential participation of numerous subcellular mechanisms. Hormone secretion is
      dictated by extracellular stimuli that are transduced intracellularly into
      activation/deactivation of different mechanisms, such as hormone expression,
      processing and exocytosis, which will ultimately determine the precise
      availability of hormone to be secreted. Malfunction in any of these steps may
      result in deficient or excessive hormone release and the subsequent appearance of
      endocrine disorders. Given the complexity of this system, it is difficult to find
      appropriate cellular models wherein to investigate the multiple components of the
      secretory process in a physiologically relevant, experimentally manipulable
      setting. In this review, we present recent evidence on the use of the
      intermediate lobe (IL) of the pituitary as a powerful tool to understand
      different aspects of the regulated secretory pathway. IL is composed of a single
      endocrine cell type, alpha-melanocyte stimulating hormone (alpha-MSH)-producing
      melanotropes, a fact that greatly facilitates its study. Furthermore,
      melanotropes can be separated using classic cell separation techniques into two
      cell subtypes showing opposite morphophysiological phenotypes of hypo- and
      hypersecretory cells. Comparison of their gene expression fingerprints has
      unveiled the existence of certain genes preferentially expressed in each
      melanotrope subtype. Because of their direct participation in the secretory
      pathway, we postulate that characterization of these gene products in an
      endocrine cell type may represent novel and useful markers for reliably
      determining the general secretory status in an endocrine gland, as well as a
      valuable new tool to further investigate this complex process.

PMID- 16419505
TI  - [Footwear].

PMID- 16419506
TI  - [Deformities and deviations of the feet and their consequences].

PMID- 16419507
TI  - [The podiatric pathology of nail. The chronic nail dystrophies].

PMID- 16419509
TI  - [Practical index card: surgery in podiatry].

PMID- 16419508
TI  - [What are the surgical indications in podiatry?].

PMID- 16419510
TI  - [Pedicure and podiatric care].

PMID- 16419511
TI  - [Index card: pedicure and podiatric care].

PMID- 16419512
TI  - [Diabetic foot : attention, danger! ].

PMID- 16419513
TI  - [The different profile patients and their pathologies. Synthesis].

PMID- 16419514
TI  - [Item no 50: complications of decubitus immobilization. Prevention and
      management: decubitus ulcer].

PMID- 16419515
TI  - [Item no 79: cutaneous ectoparasites: mange and pediculosis].

PMID- 16419516
TI  - [Item no 84: herpes virus infection in immunocompetent children and adults:
      cutaneous and mucous herpes].

PMID- 16419517
TI  - [Item no 84: herpes virus infections in immunocompetent children and adults:
      varicella and zona].

PMID- 16419518
TI  - [Item no 85: HIV infection: cutaneous-mucous manifestations of primary HIV
      infection].

PMID- 16419519
TI  - [Item no 87: cutaneous-mucous bacterial and fungal infections: impetigo,
      folliculitis/boil, erysipelas].

PMID- 16419520
TI  - [Item no 87: cutaneous-mucous bacterial and fungal infections: Candida albicans].

PMID- 16419521
TI  - [Item no 87: cutaneous-mucous bacterial and fungal infections: dermatophyte
      infections of facial skin, skin folds].

PMID- 16419522
TI  - [Item no 94: eruptive diseases of children].

PMID- 16419524
TI  - [Item no 95: sexually transmitted diseases: primary and secondary syphilis].

PMID- 16419523
TI  - [Item no 95: sexually transmitted diseases: gonococcal and Chlamydia trachomatis
      urogenital infections (other than Nicolas-Favre disease)].

PMID- 16419525
TI  - [Item no 114: cutaneous-mucous allergies in children and adults: urticaria and
      Quincke edema].

PMID- 16419526
TI  - [Item no 114: cutaneous-mucous allergies in children and adults: atopic
      dermatitis].

PMID- 16419527
TI  - [Item no 114: cutaneous-mucous allergies in children and adults: contact eczema].

PMID- 16419528
TI  - [Item no 116: autoimmune bullous dermatoses].

PMID- 16419529
TI  - [Item no 117: disseminated lupus erythematosus. Antiphospholipid syndrome].

PMID- 16419530
TI  - [Item no 123: psoriasis].

PMID- 16419531
TI  - [Item no 124: sarcoidosis].

PMID- 16419532
TI  - [Item no 127: organ transplantation: cutaneous complications].

PMID- 16419533
TI  - [Item no 137: leg ulcer].

PMID- 16419534
TI  - [Item no 149: epithelial and melanoma skin tumors: skin carcinoma].

PMID- 16419535
TI  - [Item no 149: epithelial and melanoma skin tumors: tumors due to human
      papillomavirus].

PMID- 16419536
TI  - [Item no 149: epithelial and melanoma skin tumors: melanoma].

PMID- 16419537
TI  - [Item no 149: epithelial and melanoma skin tumors: nevus].

PMID- 16419538
TI  - [Item no 164: malignant lymphoma: cutaneous lymphoma].

PMID- 16419540
TI  - [Item no 181: iatrogenic disease. Diagnosis and prevention: drug eruptions].

PMID- 16419539
TI  - [Item no 174: prescription and surveillance of steroidal and non-steroidal anti
      inflammatory agents: dermal corticoid treatment].

PMID- 16419542
TI  - [Angiomas].

PMID- 16419541
TI  - [Item no 205: acute red swollen leg].

PMID- 16419544
TI  - [Rosacea].

PMID- 16419543
TI  - [Acne].

PMID- 16419545
TI  - [Seborrheic dermatitis].

PMID- 16419546
TI  - [Alopecia].

PMID- 16419547
TI  - [Onyxis].

PMID- 16419548
TI  - [Exanthema].

PMID- 16419549
TI  - [Erythroderma].

PMID- 16419550
TI  - [Raynaud's phenomenon].

PMID- 16419551
TI  - [Pruritus].

PMID- 16419552
TI  - [Purpura in children and adults].

PMID- 16419553
TI  - [Ulceration or erosion of the mouth mucosa and/or genitals].

PMID- 16419554
TI  - Correlates of unsafe syringe acquisition and disposal among injection drug users
      in Baltimore, Maryland.
AB  - Because multi-person syringe use is the most common vehicle for HIV and hepatitis
      C virus transmission among injection drug users (IDUs), safe sources of sterile
      syringes and safe methods of disposal are necessary to curb these epidemics. We
      examined syringe acquisition and disposal in a cohort of IDUs in Baltimore.
      Between January 1, 1998 and December 31, 2001, 1034 participants reported on
      syringe acquisition at 3492 visits, and 953 reported on disposal at 2569 visits.
      Participants were 69.9% male, 93.9% African-American, and median age was 44.
      Syringes were acquired exclusively from unsafe sources at 32.3% of visits, while
      exclusively unsafe disposal was reported at 59.3% of visits. Significant
      correlates of unsafe acquisition were: attending shooting galleries, anonymous
      sex, sharing needles, smoking crack, and emergency room visits. Significant
      correlates of unsafe disposal were: injecting speedball, no methadone treatment,
      acquiring safely, and frequent injection. Having a primary source of medical care
      was associated with safe acquisition, but unsafe disposal. IDUs continue to
      acquire safely but dispose unsafely, especially among those with a primary source
      of care; this suggests that messages about safe disposal are not being
      disseminated as widely as those about acquisition. These data suggest the need
      for a more active program involving pharmacists, an expanded syringe access
      program, and better efforts to enhance safe disposal.

PMID- 16419555
TI  - Dual diagnosis and quality of life in patients in treatment for opioid
      dependence.
AB  - This study examined the relationship between quality of life (QOL) and dual
      diagnosis among patients in treatment for opioid dependence. The study sample
      includes 57 patients with opioid dependence alone (OD) and 41 with opioid
      dependence and a psychiatric axis-I disorder (DD), recruited in 2001 and 2004 at
      the Drug Addiction Services (SerT) of Bolzano and Pontedera (Italy). Participants
      were 73.5% males, with a mean age of 35.1 years (SD = 8.0). A comparison group of
      45 healthy controls was also included. Assessments included a structured
      psychiatric interview (SCID) and a self-report quality of life assessment (WHOQOL
      BREF). Patients with DD reported significantly (p < 0.05) poorer QOL in the
      physical and psychological domains as compared with patients with OD. Both groups
      of patients with and without DD showed significantly (p < 0.001) poorer QOL in
      the physical, psychological, and social domains with respect to healthy
      participants. The scores on the "relationship with environment" domain did not
      differ among OD, DD, and controls. The present study provides preliminary
      evidence that dual diagnosis is associated with poorer QOL and emphasizes the
      need to target treatment for the mental disorder concomitantly with the
      dependence problem in patients in treatment for opioid dependence.

PMID- 16419556
TI  - The use of legal coercion in the treatment of substance abusers: an overview and
      critical analysis of thirty years of research.
AB  - Drug and alcohol use presents a serious social problem for most countries in the
      world. Of particular concern is the well-documented relationship between
      substance use and crime, which has contributed to an increased popularity and
      willingness to utilize more forceful means to pressure substance users into
      treatment. Although compulsory/legally mandated treatment is appealing, it has
      been one of the most fiercely debated topics in the addiction field, raising a
      number of issues including ethical concerns and motivational considerations. In
      this context, the most important question to be answered is whether or not
      compulsory treatment is effective in the rehabilitation of addicted offenders.
      Regrettably, three decades of research into the effectiveness of compulsory
      treatment have yielded a mixed, inconsistent, and inconclusive pattern of
      results, calling into question the evidence-based claims made by numerous
      researchers that compulsory treatment is effective in the rehabilitation of
      substance users. The present paper provides an overview of the key issues
      concerning the use and efficacy of legal coercion in the rehabilitation of
      substance users, including a critique of the research base and recommendations
      for future research.

PMID- 16419557
TI  - Negative self-perceptions and sexual risk behavior among heterosexual
      methamphetamine users.
AB  - This research examined the relationship between negative self-perceptions and
      sexual risk behavior in a sample of 156 heterosexually identified,
      methamphetamine users from San Diego, California. The Beck Depression Inventory
      and the Self Esteem Rating Scale, respectively, were used to assess depression
      and negative self-perceptions. Measures of sexual risk behavior and
      methamphetamine use were developed specifically for this research. Data were
      gathered in 2001-2002. Participants were primarily male (76%), Caucasian (56%),
      never married (51%), and unemployed (73%), with a mean age of 39.1 years.
      Participants with high levels of negative self-perceptions evidenced the greatest
      degree of sexual risk behavior, including significantly more unprotected vaginal
      sex and a larger number of sexual partners as compared to individuals with low
      levels of negative self-perceptions. In cross-sectional analyses, negative self
      perceptions predicted intensity of methamphetamine use and depressive symptoms.
      However, neither of these variables were found to mediate the relationship
      between negative self-perceptions and sexual risk behavior. Findings are
      discussed in relation to the need for further research into the role of negative
      self-perceptions as a determinant of sexual risk behavior among methamphetamine
      users.

PMID- 16419558
TI  - Residential substance user treatment programs as venues for HCV pharmacological
      treatment: client and staff perspectives.
AB  - Hepatitis C virus (HCV) infection is highly prevalent among drug users. While
      there are antiviral medications available to combat the virus, the medication
      regimen is quite arduous, presenting special issues for drug users. We examined
      the challenges and benefits of using residential substance user treatment
      programs as venues for clients to undergo HCV medication regimens. Analyses of
      qualitative data collected from clients and staff in 2003 at four residential
      substance user treatment programs in the U.S. indicate that challenges primarily
      include issues involving the medications' side effects, and both financial and
      communication concerns. Benefits especially involve clients' feelings that they
      are being proactive in addressing health issues in an environment that provides
      much-needed support. Findings illuminate the complex issues involved for both
      clients and the programs, and some steps that programs can take to better support
      HCV-infected clients regarding HCV medication concerns.

PMID- 16419559
TI  - The impact of a self-help pamphlet on reducing risk drinking among 30- to 49-year
      old men in Helsinki, Finland.
AB  - This study evaluates the impact of a self-help pamphlet designed to support self
      control of drinking. It was conducted in Helsinki, Finland, in 2001 and 2002 and
      focused on men between 30 and 49 years of age. The respondents were randomly
      selected in an intervention and a control area and compared with each other
      before and after the intervention using independent samples (N = 4418) The
      results support previous findings showing that interventions like this serve as a
      supplement to other prevention and early treatment measures. Although the results
      were encouraging, there is a need for more in-depth studies in the field.

PMID- 16419560
TI  - Prevalence and predictors of "heavy" marijuana use in a Canadian youth sample.
AB  - In this investigation, secondary analyses were performed on an extensive database
      for 473 biological and 128 adoptive families. These data, which were gathered as
      part of the Vancouver Family Survey, were used to examine the prevalence and
      predictors of "heavy" marijuana use in a Canadian youth sample aged 14-25.
      Results in this study showed that 12.6% of the sample reported using marijuana
      once a week or more. These respondents were categorized as "heavy" marijuana
      users. Higher levels of life problems were associated with this use pattern.
      Results from a series of regression analyses suggested that the family,
      personality, and peer domains all contributed significantly in predicting "heavy"
      marijuana use. Father's alcoholism and peer illicit drug use had direct
      relationships with heavy marijuana use in this final model. A possible mediated
      pathway was also suggested with the Addiction Prone Personality influencing use
      through its relationship with heavier peer drug use.

PMID- 16419561
TI  - Adolescent substance use assessment: concordance between tools using self
      administered and interview formats.
AB  - The present study evaluates the agreement between adolescent self-report of
      substance use frequencies obtained from a self-administered questionnaire vs.
      face-to-face interview formats. Participants were 108 adolescents (82 males, 26
      females), aged 11 to 19 (M = 15.74, SD = 1.17), who were referred for a chemical
      dependence assessment between June of 1999 and June of 2000 in Minnesota. The
      adolescent battery included the self-administered Personal Experience Inventory
      and the face-to-face interviewer-administered Drug Use History Interview to
      assess substance use frequency. A urine sample was also collected to validate
      self-report of recent substance use. Bivariate correlations between adolescent
      self-report on the self-administered and interviewer-administered formats were
      strong for alcohol (average r = 0.72) and marijuana (average r = 0.81) use
      frequencies during the 3 months and 12 months preceding the baseline assessment.
      However, adolescents were generally more likely to report greater frequencies of
      alcohol and marijuana use during the interview-administered protocol when
      compared to the self-administered format. Study implications and limitations are
      discussed.

PMID- 16419562
TI  - Users' experiences of heroin and methadone treatment.
AB  - The present study, conducted in 2003, Melbourne, Australia, examined and compared
      how different personal and social resources related to participants' use of both
      heroin and methadone, as well as their experiences of stigma and program
      regulation, and their evaluation of methadone treatment. In-depth interviews were
      conducted with 10 participants (five men, five women) aged between 25 and 42.
      Participants who had diverse personal and social circumstances were purposefully
      sought. Findings showed that users with "non-addict" or "functional" self
      concepts had more resources and supportive social relationships that assisted
      them to develop realistic treatment expectations, avoid the stigma associated
      with methadone, and focus on the benefits of the treatment. Conversely,
      "conflicted" users with limited resources, few social connections, and negative
      self-concept saw methadone as an addiction, and as a highly stigmatizing and
      disempowering intervention. Social policies that differentiate users and address
      ways of improving users' personal and social resources are now needed.

PMID- 16419563
TI  - Self-efficacy and emotional adjustment as precursors of smoking in early
      adolescence.
AB  - The aim of this study was to examine the associations between self-efficacy,
      emotional adjustment, and smoking in a large sample of early adolescents cross
      sectionally and short-term longitudinally. A prospective sample was used
      consisting of 1861 12-13-year-olds at 11 secondary schools. Questionnaires were
      administered at baseline and at a follow-up 6 months after the baseline
      assessment. Findings showed that higher depressive mood, low self-esteem, and low
      self-efficacy appeared to be related to enhanced levels of smoking in cross
      sectional analyses. Short-term longitudinal analyses indicated that depressive
      mood and self-esteem were only related to the onset of smoking in girls. In three
      out of four cross-sectional analyses, self-efficacy x emotional adjustment
      interactions revealed that in particular adolescents with low levels of self
      efficacy and low levels of emotional adjustment are likely to smoke.

PMID- 16419564
TI  - [Blood interleukin-6 level in children with idiopathic headaches].
AB  - AIM: Neurogenic inflammation may contribute to the pathogenesis of migraine. IL-6
      plays an important role as a proinflammatory cytokine. The aim of this research
      was to investigate IL-6 level changes in children with migraine and episodic
      tension-type headache (ETTH) at baseline and during a headache attack, and also
      factors which may influence these changes (aura, sex, weight, leukocyte and
      thrombocyte count). MATERIALS AND METHODS: In 30 children with migraine, 31 with
      ETTH and 28 controls without headaches, an IL-6 level was established in plasma
      using Biosource kit in the first, third and sixth hour of headache, and 6 hours
      after its termination. Two days after pain termination, the headache-free
      measurements were analyzed, and under the same conditions in controls. A
      statistical assessment was performed. RESULTS: In 12/30 children with migraine
      there was an increase in the IL-6 level in the first hour of the attack. There
      were no differences between migraine with and without aura, migraine and ETTH,
      and between headaches at baseline and controls. There was an increase in the IL-6
      level in children with prolonged primary headaches (migraine and ETTH) in the
      third and sixth hour of the attack. No correlation between IL-6 and sex, count of
      leukocytes and thrombocytes was established. CONCLUSION: The increase in the IL-6
      level in several children with migraine in the first hour of the attack may
      suggest that neurogenic inflammation contributes to the migraine pathogenesis. IL
      6 is not involved in the pathogenesis of ETTH. The increase in the IL-6 level in
      children with prolonged headache may reflect a stress reaction.

PMID- 16419565
TI  - [Photosensitivity in children with idiopathic headaches].
AB  - The occipital lobe involvement in the pathogenesis of the migraine aura, frequent
      occurrence of photogenic stimuli as the provoking factors of a migraine attack,
      still unsatisfactory explanation of the relation between migraine and epilepsy
      have drawn our attention to the photosensitivity in the idiopathic headaches,
      particularly in the developmental period. Photosensitivity is detected in EEG as
      a paroxysmal response to intermittent photic stimulation. This reaction called a
      photoparoxysmal response (PPR) has to be regarded as genetically determined EEG
      symptom and occurs in 1.3-1.4% of healthy individuals aged 6-18. The aim of the
      study was to compare the frequency and identify the type of PPR in idiopathic
      headaches in children: with migraine with aura, without aura and with tension
      type headache as well as to find the possible correlation between PPR and
      migraine photogenic triggering factors in children and adolescents aged 7-18. In
      years 2001-2003 263 EEG records were performed in patients hospitalized because
      of idiopathic headaches: 77 with the diagnosis of migraine with aura, 112 -
      migraine without aura, 74--in tension-type headache. The Fisher exact test was
      used to compare the number of patients with positive PPR and those with
      photogenic triggering factors of a migraine attack. The frequency of PPR did not
      differ significantly in three types of idiopathic headaches and accounts for 7.8%
      in migraine with aura, 8.9%--migraine without aura and 6.7%--in tension-type
      headache. PPR was most frequent (17.6%) in a group of children under 12 years of
      age with migraine with aura. In the migraine with aura PPR had the form of the
      general paroxysmal of the spike, polyspike and wave in 11.8%, localized changes
      in the temporal-parietal-occipital region only in 5.9%. In 7/17 patients with
      migraine and PPR, photogenic stimuli were most frequent provoking factors for the
      migraine attack (in controls without PPR 10/100) (p<0,01). Frequent coexistence
      of PPR and photogenic provocation of the migraine attack in children and
      adolescents supports the theory about general cortical hyperexcitability in
      migraine.

PMID- 16419566
TI  - [The study of early auditory evoked potentials in primary headaches in children
      and adolescents and their pathogenetic implications].
AB  - Neurophysiological examinations, especially auditory evoked potentials which
      enable us to make the neurophysiological evaluation of the auditory pathway play
      an important role in the explanation of pathophysiology of primary headaches,
      especially migraine. The functional neuroimaging studies in patients with
      migraine during pain attacks have shown the activation of brainstem. It is
      suggested that the appearance of photophobia in patients with migraine may be
      related to the disturbances of brainstem functions. The aim of the studies was to
      evaluate the brainstem auditory evoked potentials (BAEP) in children with primary
      headaches. The obtained results were interpreted with consideration of the
      complex pathomechanism of migraine. MATERIAL AND METHODS: 125 patients
      participated in these examinations with 90 ones with migraine and 35 ones with
      tension-type headache (TTH), diagnosed according to the criteria of the
      International Headache Society (IHS). The control group for neurophysiological
      examinations consisted of 66 healthy children and adolescents of the same age.
      BAEP were recorded using 4-channel Multiliner (Toennies, Germany). The following
      parameters were evaluated: morphology of the recording, absolute latencies of I
      to V waves and interlatencies between I-III, III-V and I-V. RESULTS: Essential
      prolongation of latencies in III and IV waves of BAEP was found only in patients
      with migraine, especially with visual aura. They were significant in comparison
      to latencies obtained in children with TTH and in the control group. No
      correlations between the clinical data from patients with migraine and TTH, and
      neuropsychological parameters were found. CONCLUSIONS: 1. The significant
      prolongation of III and IV wave latencies of BAEP was found in migraine patients
      only. The obtained results suggest that the brainstem contributes to the
      pathomechanism of these headaches. 2. The BAEP recordings in children and
      adolescents with TTH were not different from the parameters obtained in healthy
      children.

PMID- 16419567
TI  - [Visual evoked potentials in children and school adolescents with migraine and
      tension-type headache. Clinical and neurophysiological correlations].
AB  - To differentiate clinically migraine, especially without aura, from tension-type
      headache (TTH), especially an episodic one, in patients in the developmental age
      may become a difficult task. The reason is the similarities of clinical symptoms
      in both types of headaches. The results of examinations published so far do not
      explain satisfactorily the pathomechanism and clinical symptoms of primary
      headaches. Therefore, it makes scientists apply more and more recent research
      methods to explain their pathophysiology. The aim of the study in children and
      adolescents with migraine and TTH was to evaluate the diagnostic values of visual
      evoked potentials (VEP). Clinical and neurophysiological correlations in primary
      headaches were also noted. MATERIAL AND METHODS: 90 patients with migraine and 35
      with TTH aged 8-18 participated in the study. The control group for
      neurophysiological examinations consisted of 66 healthy children and adolescents
      of the same age. VEPs were performed in the pain-free interval using 4-channel
      Multiliner (Toennies, Germany). The parameters for analysis were: latencies P100,
      N75, N145, amplitudes N75/P100, P100/N145 and interocular and interhemispheric
      differences. RESULTS: Substantial prolongation of P100 and N145 latencies and
      reduction of N75/P100, P100/N145 amplitudes were recorded in one hemisphere only
      in patients with migraine. Correlations between VEP and age, duration of the
      disease and the frequency of migraine attacks were found. Presence and type of
      existing aura did not change values of recorded parameters in VEP CONCLUSIONS:
      The changes in VEP parameters were observed only in patients with migraine. The
      statistically significant interhemispheric differences without interocular
      changes point to their unilateral localization of the neuronal changes in visual
      pathway. The positive clinical and neuropsychological correlations obtained in
      migraine may be related to the vascular theory of migraine.

PMID- 16419568
TI  - [Usefulness of cerebral SPECT in the children with migraine].
AB  - The aim of the study was to evaluate the regional cerebral blood flow (rCBF)
      occurring interictally in children with migraine using SPECT The study included
      30 patients (16 boys and 14 girls) aged 8-16 with migraine with and without aura
      during attacks. SPECT scans were performed after i. v. injection of 99mTc-ECD of
      0.3 mCi/kg b.m. Uptake of the tracer was determined in different regions of
      interest in the cortex. 11 patients showed homogenous distribution over all
      cortical regions and rCBF expressed as a cerebral/cerebellar ratio was within the
      normal range. Reduced perfusion and asymmetry ranging between the right and left
      hemisphere within 7-10% was observed in 19 out of 30 patients with migraine
      attacks. In all these 19 cases we observed localization of hypoperfused foci in
      SPECT imaging matched with the side of migraine pain. CONCLUSIONS: The interictal
      rCBF is both reduced and asymmetric in children suffering from migraine and the
      side of migraine pain is in accordance with the localization of hypoperfusion in
      SPECT.

PMID- 16419569
TI  - [Headache occurrence and assessment of regional blood flow after brain concussion
      in children].
AB  - BACKGROUND AND PURPOSE: Headaches which can last for many months and even years
      belong to the most frequent consequences of closed head injuries in children. The
      method which makes it possible to demonstrate the presence and extent of the
      nervous tissue damage caused by trauma is the regional cerebral blood flow (rCBF)
      evaluation with single photon emission computerized tomography (SPECT). In the
      present study the regional cerebral blood flow (rCBF) was assessed 10-15 days
      after trauma, 3 months and one year in cases of brain concussion. We tried to
      establish whether there was a correlation between changes in rCBF and the
      occurrence of posttraumatic headache. MATERIAL AND METHODS: SPECT was applied in
      32 children, aged 6-16, 10-15 days, and then 3 and 12 months after brain
      concussion. In all children no changes were found in CT and MRI examinations.
      RESULTS: In the studied group in the early period after trauma, blood flow
      impairment was found in 21 children, mostly in frontal areas. One year after
      trauma the rCBF improved in 11 children, in 10 cases the pattern was normal. In a
      group of 4 children with headache one year after brain concussion, three of them
      still presented the impairment of blood flow. CONCLUSIONS: SPECT shows a great
      sensitivity and usefulness in the assessment of consequences of head trauma and
      it can explain some posttraumatic complaints in children.

PMID- 16419570
TI  - [Chronic post-traumatic headache and brain perfusion changes assessed using
      magnetic resonance imaging].
AB  - BACKGROUND AND PURPOSE: Headache after a head injury is one of the most frequent
      symptoms in patients after craniocerebral trauma. The aim of the study was to
      investigate changes in brain perfusion in patients with chronic post-traumatic
      headache a long time after craniocerebral trauma. PWI gives us the exact
      information about the brain circulation. MATERIAL AND METHODS: Clinical measures
      included 52 patients (24 women and 28 men) aged from 20 to 56 years (mean age
      42.3 years) suffering from chronic post-traumatic headache after moderate and
      severe craniocerebral trauma, 6-18 months after the head injury. The Glasgow Coma
      Scale (GCS) and Abbreviated Injury Scale (AIS) were used to evaluate the severity
      of the head injury. The PWI (Perfusion Weighted Imaging) study was made in all
      patients. RESULTS: In the study group in the PWI study the domination of
      perfusion disturbances in frontal lobes were seen in 38 patients (59.6%).
      Statistical analysis showed no significant correlation between character,
      intensity, localization of headache and changes in the PWI. In 22 patients with
      localized headache the highest percentage of changes in PWI matched with
      localization of headache were observed in frontal lobes--40.9% in the right
      frontal lobe, 31.8% in the left frontal lobe, and in the right temporal lobe-
      22.7%. In accessible references no publications concerning changes in the PWI in
      chronic post-traumatic headache were found. CONCLUSIONS: The results suggest the
      occurrence of brain perfusion disturbances a long time after craniocerebral
      trauma, which were most marked in frontal lobes, without any statistically
      significant correlation with chronic post-traumatic headache.

PMID- 16419571
TI  - [Migraine and irritable bowel syndrome].
AB  - The association between migraine and functional gastrointestinal disorders has
      been confirmed by many clinical observations and epidemiological studies. In most
      patients during the attacks of migraine, apart from various neurological and
      vascular symptoms, gastrointestinal disturbances occur including nausea,
      vomiting, abdominal pain or diarrhea. Functional gastrointestinal disorders, such
      as irritable bowel syndrome (IBS), are reported in migraine patients in periods
      between the attacks as well. On the other hand 23-53% of IBS patients have
      frequent headaches. Migraine and IBS often coexist with fibromyalgia and other
      chronic pain syndromes and functional disorders. Migraine and IBS affect
      approximately 10-20% of the general population, usually young adults. Both
      diseases are more prevalent in women, perhaps due to the role of estrogen in
      their pathogenesis. Looking for the common pathogenetic mechanisms of IBS and
      migraine the role of the brain-gut axis, neuroimmune and neuroendocrine
      interactions are being considered. The influence of stress on symptom occurrence
      and severity seems to be associated with hyperactivity of the hypothalamic
      pituitary-adrenal axis. The enteric nervous system as a source of numerous
      neurotransmitters and visceral reflexes is a plausible common pathogenic link
      between IBS and migraine. In particular serotonin being the main neurotransmitter
      of the gastrointestinal tract plays a relevant role in the pathogenesis of IBS as
      well as migraine. Nowadays, agonists and antagonists of serotoninergic receptors
      are the most efficacious drugs for IBS and migraine therapy. Some side effects of
      triptans, 5-HT(1B/D) agonists, used in migraine treatment may be connected with
      the influence of triptans on the gastrointestinal functions. A better
      understanding of the relationship between migraine and IBS may result in more
      effective treatment of both diseases.

PMID- 16419572
TI  - [Is migraine a neuronal channelopothy?].
AB  - Over the past 15 years an increasing awareness of the role of mutant ion channels
      in the pathogenesis of episodic neurological disorders has emerged. Molecular
      characteristic of genetic channelopathies, that are rare and monogenic,
      contributed to a better understanding of abnormalities in common episodic
      diseases such as migraine and epilepsy. Familial hemiplegic migraine, a rare
      autosomal dominant subtype of migraine with aura, is the first evidence
      implicating migraine as a neuronal channelopathy.

PMID- 16419573
TI  - [Basilar-type migraine: pathophysiology, symptoms and signs, and treatment].
AB  - Basilar-type migraine (BTM) is a type of migraine with aura symptoms resulting
      from brain stem or bi-hemispheric structures but without motor elements. There
      are no precise data on the frequency of BTM. The main cohort of the patients
      includes young people and children with female predomination. The onset of the
      disease usually occurs before the age of 25. The diagnosis of BTM is based on the
      finding of two migraine attacks accompanied by a specific aura, with dysarthria,
      vertigo, tinnitus, impaired hearing, double vision, visual aura elements, ataxia
      of a cerebellar type, loss of consciousness, and bilateral paresthesias. In the
      differential diagnosis one should consider the pathology of posterior fossa,
      diseases with recurrent vertigo, complex epileptic seizures, CADASIL and MELAS
      syndromes, and alternative hemiplegic migraine with cerebellar symptoms and
      signs. In the prophylaxis sodium valproate and calcium-entry blockers and,
      especially in the prophylaxis of vertigo, betahistine chloride are used.

PMID- 16419574
TI  - [Triptans in migraine--here and now (15 years after they were implemented in
      therapy)].
AB  - Migraine is one of the most common primary/idiopathic headaches as well as one of
      the most frequent complaints in the society. For the last 15 years there has been
      a significant change in the acute treatment of migraine attacks. It was a result
      of an extensive research on serotonin receptors, primarily their 5-HT(1B) and 5
      HT(1D) subtypes, and on the pathological mechanisms underlying migraine headache.
      New drugs acting selectively, triptans, are not only more effective than
      traditional medicaments, common pain-killers (NSAID) and ergotamine, but are also
      much safer than non-selective and high affinity pharmaceuticals and ergotamine,
      which binds for a long time the 5-HT receptors, predominantly in the coronary
      arteries. The review shows main differences between particular triptans and
      discusses the principles of therapy, including contraindications.

PMID- 16419575
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyI-L-proline): II. Introduction.
AB  - The consumption of fermented milk to maintain good health, including the
      maintance of normal blood pressure, is an ancient tradition in a number of areas
      of the world (e.g., East Asia, France). Recent studies have suggested that
      fermented milk has a normotensive effect in hypertensive rats and humans, but no
      effect on blood pressure in normotensive rats and humans. Two tripeptides, L
      valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP), have
      been identified as possessing significant angiotensin-converting enzyme
      inhibitory activity and are therefore believed to be the source of the
      normotensive effects. This document, the second of nine chapters, provides
      information on these two tripeptides, including physical/chemical properties,
      molecular weights, chemical structures, normal consumption in the diet,
      manufacturing information, regulatory approval in Japan, and Japanese consumption
      of food containing enhanced levels of VPP plus IPP. In addition, the results of
      studies in rats and humans conducted to evaluate the effect of these substances
      on blood pressure are presented. The research suggests that in adult normotensive
      volunteers, consumption of up to 7.92 mg of VPP and 4.52 mg IPP daily for 2 weeks
      causes neither clinical signs nor biologically meaningful effects on systolic or
      diastolic blood pressure, pulse rate, or clinical pathology (serum chemistry or
      hematology). However, when a similar study was performed using mildly and
      moderately hypertensive adults as subjects and they consumed 2.52 mg of VPP and
      1.64 mg of IPP per day, a significant drop in systolic blood pressure was
      detected for a prolonged time interval. This chapter also introduces the issue of
      safety testing for these substances and describes the information to be found in
      the subsequent seven chapters.

PMID- 16419576
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): III. Single- and/or repeated-dose toxicity
      of tripeptides-containing Lactobacillus helveticus-fermented milk powder and
      casein hydrolysate in rats.
AB  - The objective of these studies was to assess the toxicological potential of
      orally administered tripeptides in rats. The studies employed powdered L-valyl-L
      prolyl-L-proline (VPP)- and L-isoleucyl-L-prolyl-L-proline (IPP)-containing test
      articles, including (1) powdered Lactobacillus helveticus-fermented milk (FM),
      (2) pasteurized casein hydrolysate (CH) generated by Aspergillus oryzae protease,
      and (3) synthesized VPP. All test articles were administered by oral gavage to
      male and female Sprague-Dawley rats. Specific goals of the single-dose and
      repeated-dose studies were to (1) identify doses that produce evidence of
      systemic and/or local (i.e., gastrointestinal) toxicity (e.g., lowest-observable
      effect level [LOEL]); (2) estimate the maximally tolerated oral dose (MTD); and
      (3) identify specific target organs for toxicity of these tripeptides. Single
      doses of CH (2000 mg/kg), powdered FM (2000 or 4000 mg/kg), or VPP (40, 200, or
      400 mg/kg) were administered 14 days prior to study termination. No treatment
      regimen caused either antemortem (gross observations, body weight, and food
      consumption parameters) or postmortem (necropsy) evidence of either systemic or
      local toxicity. In the repeated-dose study, powdered FM (0, 500, 1000, or 2000
      mg/kg body weight [BW]/day) was administered by gastric gavage to male and female
      rats for 28 consecutive days. Antemortem evaluative parameters included gross
      observations, ophthalmic examinations, and clinical pathology (clinical
      chemistry, hematology, and urinalysis). Post mortem parameters included necropsy,
      determination of organ weights, and microscopic examination of major organs.
      There was neither in-life nor postmortem evidence that powdered FM administration
      caused physiological or toxicological changes. Under the conditions of these
      experiments, the single-dose LOEL of powdered FM, CH, and VPP were found to be
      greater than 4000, 2000, and 400 mg/kg, respectively. The results of the repeated
      dose study do not support identification of a target organ for powdered FM
      toxicity. Similarly, there was no evidence to support establishment of either the
      LOEL or MTD; both being greater than 2000 mg/kg/day for up to 28 consecutive
      days.

PMID- 16419577
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): IV. Assessment of the repeated-dose
      toxicological potential of synthesized L-valyl-L-prolyl-L-proline in male and
      female rats and dogs.
AB  - The objective of these repeated-dose, 8-week studies was to assess the
      toxicological potential of a synthetic tripeptide, L-valyl-L-prolyl-L-proline
      (VPP), when administered to Charles River rats and Beagle dogs. Groups of 20 male
      and 20 female rats were fed powdered diets containing sufficient VPP to afford
      daily doses of 0, 2, 8, or 16 mg/kg body weight (BW)/day. Groups of five male and
      five female dogs were administered 0, 2, 8, or 16 mg/kg BW/day in hard gelatin
      capsules. Antemortem evaluative parameters for both species included grossly
      observable clinical signs, body weight and food consumption, clinical pathology
      (hematology, clinical chemistry, urinalysis), and ophthalmological examinations.
      Dogs also received electrocardiographic examinations. Postmortem evaluations in
      both species included complete necropsy, determination of major organ weights,
      and histopathological examination of specimens from approximately 50 organs and
      tissues. All rats and dogs survived to the scheduled termination of the studies
      and neither species exhibited evidence of VPP effects on appetite or body weight
      gain/maintenance. Ophthalmic examinations revealed occasional lens clouding in
      rats, but this occurred in all groups and was not attributable to VPP. Some
      clinical pathology parameters in both species were occasionally altered, but
      there was no evidence that this was dose-related. Electrocardiographic
      examinations in dogs revealed no VPP-associated changes. Mid- and high-dose male
      rats (but not females) had slightly reduced mean pituitary and kidney weight
      parameters, whereas mid- and high-dose females had slightly increased mean
      uterus:body weight ratios. There were no microscopic correlates for these minor
      changes. Ten percent to 20% of all female rats (but not males) exhibited
      corticomedullary mineralization of the kidney and gliosis of the optic nerve, and
      10% to 20% of males (but not females) had thymic hemorrhage. Postmortem
      evaluations of dogs revealed no VPP-related effects on organ weights or either
      macro- or microscopic appearances of organs. The results of these studies
      provided no evidence of either local or systemic toxicity. Similarly, there was
      no evidence of neurotoxicity that might have been detected by the appearance of
      physical or behavioral changes during gross observations of animals. Although
      these results do not identify target organs for VPP toxicity, the no-observable
      effect level and maximally tolerated dose are both greater than 16 mg/kg/day when
      administered to male and female rats and dogs for 8 consecutive weeks. Based upon
      food enhancement levels of VPP currently being evaluated, the resultant margin of
      safety (160) is substantial.

PMID- 16419578
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): V. A 13-week toxicity study of tripeptides
      containing casein hydrolysate in male and female rats.
AB  - The objective of this multiple-dose toxicity study was to assess the
      toxicological potential of two tripeptides, L-valyl-L-prolyl-L-proline (VPP) and
      L-isoleucyl-L-prolyl-L-proline (IPP), when administered once daily for 91
      consecutive days to rats. The test article, powdered casein hydrolysate (CH)
      known to contain 0.6% VPP plus IPP, was prepared using Aspergillus oryzae
      protease. Prior to administration to the rats by oral gavage, the test article
      was suspended in sterile water. Groups of 12 male and 12 female Charles River
      rats were administered once daily doses of 0, 40, 200, or 1000 mg of CH (0, 0.2,
      1.2, or 6 mg VPP plus IPP/kg body weight [BW]). Antemortem evaluative parameters
      included gross observations of behavior and clinical signs; food consumption and
      body weight gains; ophthalmologic examinations; clinical pathology (hematology,
      clinical chemistry); and urinalysis. Postmortem parameters included determination
      of absolute and relative (to fasting body weight) organ weights and
      histopathological evaluation of approximately 50 organs and tissues from each
      animal. All rats survived until the scheduled termination of the study and no
      treatment-related clinical signs were observed. Food consumption was unaffected
      by administration of CH. All animals gained weight and there were no statistical
      differences between groups with respect to weight gains. There were no meaningful
      changes in hematological or coagulation parameters. Mid- and high-dose males (but
      not females) had slightly (< 2%) increased mean serum chloride concentrations,
      but because the difference was so small and it was observed in only one sex, the
      authors considered its association with CH administration to be doubtful.
      Urinalysis revealed the occasional presence of crystals, leukocytes, and
      epithelial cells in animals from all experimental groups. Similarly, ophthalmic
      changes (lenticular clouding) were observed in both control and dosed animals.
      Mean relative (to body weight) kidney weight was decreased by 8% in low-dose
      males and mean relative uterus weight was elevated 46% in low-dose females.
      Absolute organ weights were not affected. Only naturally occurring microscopic
      changes were observed in all groups and none could be attributed to CH
      administration. It was concluded that, under the conditions of these experiments,
      the maximally tolerated dose (MTD) and the no-observable-effect level (NOEL) for
      powdered CH administered once daily for 13 weeks was greater than 1000 mg/kg
      BW/day or greater than 6 mg of VPP plus IPP/kg BW/day. There was no evidence of
      target organ toxicity associated with administration of the tripeptides. This
      corresponds to an margin of safety (MOS) of 60 based upon current thinking
      regarding incorporation in food.

PMID- 16419579
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): VI. Effects of Lactobacillus helveticus
      fermented milk powder on fertility and reproductive performance of rats.
AB  - The objective of these studies was to assess the effects of the tripeptides, L
      valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP), on
      reproductive capabilities of male and female rats. The specific goals of the
      experiments were (1) to determine the effects of orally administered tripeptides
      on (a) fertility and reproductive behavior in both sexes of rats, (b) embryo
      fetal development in pregnant rats, and (c) pre- and postnatal development of
      rats exposed to tripeptides in utero and during lactation; and (2) to estimate
      the no-observable-adverse-effect doses of tripeptides in maternal and fetal rats.
      During the conduct of these classical segment I, II, and III studies, the test
      material was powdered Lactobacillus helveticus-fermented milk (FM), which
      contains the tripeptides, VPP and IPP. FM (0, 500, 1000 or 2000 mg/kg body weight
      [BW]/day--equivalent to 0, 0.8, 1.6, or 3.3 mg/kg BW/day of VPP plus IPP) was
      administered to males by oral gavage from 4 weeks prior to mating until
      sacrifice, and to females from 2 weeks prior to mating through day 20 of
      lactation. Evaluative parameters included monitoring grossly observable clinical
      signs; food consumption and body weight gains; mating behavior and fertility
      indices of both sexes; implantation and maintenance of embryos; sex ratio of live
      pups; fetal viability; incidences of external, visceral or skeletal variations;
      growth and behavioral development; as well as reproductive capabilities of F1
      offspring exposed to FM during gestation and lactation. All animals were
      subjected to macroscopic examination at termination of their segment of the
      studies. Clinical signs, body weights, and food consumption were unaffected by
      administration of FM. During segment I, the test agent had no effect on estrus
      cycle, mating behavior, fertility index, or reproductive competence of either
      males or females. The results of segment II experiments revealed no effects of FM
      on postimplantation survival-loss, sex ratio or birth weights of live fetuses,
      and there was no evidence of treatment-associated developmental or teratological
      effects. During segment III, FM was without effect on pup viability, behavioral
      and sexual maturation, and reproductive capability of the F1 generation. Under
      the conditions of these experiments, the no-observable-adverse-effect level
      (NOAEL) of FM on reproductive performance in male and female rats is greater than
      2000 mg/kg BW/day, the equivalent of 3.3 mg/kg BW/day of VPP plus IPP.

PMID- 16419580
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): VII. Micronucleus test of tripeptides
      containing casein hydrolysate and Lactobacillus helveticus-fermented milk powders
      in rats and mice.
AB  - The objective of these in vivo experiments was to assess the mutagenic potential
      of tripeptides as reflected by the ability of the test compound to induce the
      formation of micronuclei in mouse polychromatic erythrocytes. The test agents
      used in these experiments were (1) powdered Aspergillus oryzae protease casein
      hydrolysate (CH) and (2) powdered Lactobacillus helveticus-fermented milk (FM).
      Both test agents contain two tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L
      isoleucyl-L-prolyl-L-proline (IPP). Male Sprague-Dawley rats (five per group)
      were administered doses of 0, 500, 1000, or 2000 mg (0, 3, 6, or 12 mg VPP plus
      IPP)/kg body weight (BW)/day CH by oral gavage for 2 days. Male CD-1 mice (six
      per group) received a single oral gavage dose of 0, 500, 1000, or 2000 mg (0,
      0.8, 1.6 or 3.3 mg VPP plus IPP)/kg BW of FM. Positive-control agents were
      cyclophosphamide (10 mg/kg, intraperitoneal [i.p.]) in rats and mitocycin C (2
      mg/kg, i.p.) in mice. Twenty-four hours after the second dose of CH, or the dose
      of cyclophosphamide to rats, or FM or mitocycin C to mice, bone marrow cells were
      fixed and examined for the presence of polychromatic erythrocytes (PCEs) and the
      presence or absence of micronucleated PCEs (MNPCEs). Administration of CH to rats
      and FM to mice produced neither changes in body weights nor signs of systemic
      toxicity. Similarly, neither CH nor FM caused statistically significant
      variations in the incidences of either PCEs or MNPCEs. Both positive-control
      agents caused unequivocal increases in the incidence of MNPCEs and
      cyclophosphamide significantly reduced the percent of rat erythrocytes appearing
      as PCEs. The results of these micronucleus assays conducted with either powdered
      CH or FM in rats and mice, respectively, show that neither form of the
      tripeptides possesses the potential to induce micronuclei formation in these
      rodent species.

PMID- 16419581
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): VIII. Assessment of cytotoxicity and
      clastogenicity of tripeptides-containing casein hydrolysate and Lactobacillus
      helveticus-fermented milk powders in Chinese hamster lung cells.
AB  - The objective of this chromosomal aberration test was to assess the mutagenic
      potential of tripeptides by determining their ability to induce chromosomal
      aberrations in cultured Chinese hamster lung (CHL) cells. The test agents used in
      these experiments were (1) powdered casein hydrolysate (CH) and (2) powdered
      Lactobacillus helveticus-fermented milk (FM). Both test agents contain two
      tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline
      (IPP). CHL cells were cultured and exposed in the presence or absence of a rat
      hepatic metabolizing system (S9); CH or FM (1250, 2500, 5000 microg/ml of
      incubation medium); or positive-control agents, mitomycin C (0.1 or 0.05
      microg/ml) or benzo(a)pyrene (20 microg/ml). In experiments with CH, cells were
      incubated for 6 h (either in the presence or absence of S9) or for 24 h (without
      S9). In experiments with FM, the cells were incubated for 6 h (either in the
      presence or absence of S9) or for 24 or 48 h (without S9). Neither short-term nor
      continuous exposure to either CH or FM caused the induction of significant
      changes in cell growth indices, incidences of chromosomal aberrations or the
      incidence of polyploids. Exposures of cells to mitomycin C and benzo(a)pyrene
      consistently resulted in the induction of the anticipated aberrant cells after
      either short-term or continuous exposures. The results of these assays support
      the conclusions that, under the conditions of these experiments, neither CH nor
      FM possesses demonstrable potential for the induction of cytotoxicity or
      clastogenesis.

PMID- 16419583
TI  - [Role of laboratory tests in early diagnosis and preventive medicine].

PMID- 16419584
TI  - [Important points in laboratory tests for early diagnosis].

PMID- 16419582
TI  - Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline
      and L-isoleucyl-L-prolyl-L-proline): IX. Evaluation of the mutagenic potential of
      synthesized L-valyl-L-prolyl-L-proline in the Salmonella-Escherichia
      coli/microsome, incorporation assay.
AB  - The objective of this study was to assess the mutagenic potential of a
      synthesized tripeptide, L-valyl-L-prolyl-L-proline (VPP), to induce mutational
      changes in Salmonella typhimurium LT2 strains TA1535, TA1537, TA98, and TA100,
      and Escherichia coli strain WP2uvrA in the classical Ames test protocol. Bacteria
      were exposed to plate concentrations of VPP of 0, 156.2, 312.5, 625, 1250, 2500,
      and 5,000 microg/plate in distilled water, in the presence and absence of Aroclor
      1254-induced rat liver homogenate preparation (S9). Positive-control agents
      included sodium azide (TA100 and TA1535); 2-aminoanthracene (TA98, TA100, TA1535,
      TA1537, and WP2uvrA); 9-aminoacridine (TA1537); 2-nitrofluorene (TA98); and N
      ethyl-N'-nitro-N-nitrosoguanidine (WP2uvrA) in DMSO. Incubations were conducted
      at 37 degrees C for about 48 h then revertant colonies were counted. All positive
      control agents were consistently and unequivocally positive, but there was no
      evidence that VPP induced increases in the incidences of revertant colonies in
      any bacterial strain with and without metabolic activation. These findings were
      replicated in a second, confirmatory test performed with and without S9. The
      results of the experiments revealed no treatment-associated changes in the
      incidence of revertant colonies in any bacterial strain tested. These results
      support a conclusion that, under the experimental conditions described, there is
      no evidence that VPP possesses mutagenic potential.

PMID- 16419585
TI  - [Significance of reference value and cut-off value in clinical laboratory tests].

PMID- 16419586
TI  - [Efficient use of clinical laboratory tests and multiphasic screening].

PMID- 16419587
TI  - [Usefulness of tumor marker in early diagnosis].

PMID- 16419588
TI  - [Present status and future prospects in genetic tests].

PMID- 16419589
TI  - [Necessary clinical laboratory tests for early diagnosis of severe pulmonary
      diseases].

PMID- 16419590
TI  - [Useful clinical tests for early diagnosis of cardiovascular diseases].

PMID- 16419591
TI  - [Useful clinical laboratory tests for early diagnosis of gastrointestinal
      diseases].

PMID- 16419592
TI  - [Useful clinical tests for early diagnosis of liver, biliary, and pancreatic
      diseases].

PMID- 16419593
TI  - [Useful clinical tests for early diagnosis of kidney and urogenital diseases].

PMID- 16419594
TI  - [Useful clinical tests for early diagnosis of hematologic disorders].

PMID- 16419595
TI  - [Useful clinical tests for early diagnosis of endocrine and metabolic disorders].

PMID- 16419597
TI  - [Useful clinical tests for early diagnosis of neuromuscular diseases].

PMID- 16419596
TI  - [Useful clinical tests for early diagnosis of collagen diseases and allergy].

PMID- 16419598
TI  - [Useful clinical tests for early diagnosis of infectious diseases].

PMID- 16419599
TI  - [Use of clinical laboratory tests for early diagnosis (discussion)].

PMID- 16419600
TI  - [Panhypopituitalism induced by xanthogranuloma of the sellar region].

PMID- 16419601
TI  - [Chronic hepatitis C with early complication of Grave's disease during the
      treatment of pegylated interferon alpha-2a].

PMID- 16419602
TI  - [Tracheobronchomalacia treated with re-stenting].

PMID- 16419604
TI  - [Endocarditis due to Listeria monocytogenes associated with aortic stenosis].

PMID- 16419603
TI  - [Successful oral ganciclovir as maintenance therapy in an acquired immune
      deficiency syndrome (AIDS) patient with cytomegalovirus (CMV) induced perforative
      colitis].

PMID- 16419605
TI  - [Evidence-based medicine in antithrombotic therapy].

PMID- 16419606
TI  - [Concept and clinical study of sepsis].

PMID- 16419607
TI  - [Necessity in accreditation of clinical-medical laboratories].

PMID- 16419608
TI  - [New era in thrombolytic therapy for cardiovascular diseases].

PMID- 16419609
TI  - Immune characterization of the Lewis rats inoculated with K2 sarcoma cell line
      and newly derived R5-28 malignant cells.
AB  - Sarcoma is a relatively rare malignant disease with high mortality, bad prognosis
      and response to conventional therapy. Two possible models of this disease were
      tested: the K2 rat sarcoma cell line, which was described previously, and the new
      rat R5-28 cell line derived from a spontaneously growing rat neoplasm with
      sarcoma morphology. While all rats inoculated with K2 cells developed tumours at
      22th-25th day after inoculation (D = 22-25), only 60%-75% of R5-28-inoculated
      rats were affected by tumours. The frequency and progress of the disease depended
      on the number of inoculated cells. No metastases were detected in both cases. All
      affected animals showed large splenomegaly. A possible response of some immune
      system components to tumours was tested. No tumour-infiltrating lymphocytes were
      revealed in the tumour tissue. Anti-tumour antibodies were not found in tumour
      bearing animal sera. Appropriate changes in peripheral blood lymphocyte subsets
      were explored. While the relative numbers of both NK cells and Tc were impaired,
      no changes were noted in numbers of CD4+CD8- T helper cells. Leukocytosis with
      highly increased numbers of CD11b+ myeloid cells displaying variable expression
      of CD4 was detected in terminal stages of the disease.

PMID- 16419610
TI  - Cytogenetic investigation of workers professionally exposed to phosphates and
      their derivatives.
AB  - The phosphor industry in Morocco employs a great number of workers that may be
      exposed to this essential but also toxic compound. In the present investigation,
      professionally exposed subjects from two different production lines (miners and
      production unit workers) were investigated for the presence of genetic damage in
      their peripheral blood lymphocytes. This was done with the well-known
      micronucleus assay. The proliferation and mitotic indices were also investigated.
      It was found that the micronucleus frequency was considerably increased compared
      to the frequency in non-exposed control subjects. Mitotic and proliferation
      indices were not increased, at least not in a statistically significant way. At
      the time being this investigation should be considered as a preliminary study in
      which the influence of potential confounders cannot be adequately assessed.
      However, our results are non-equivocal and clearly indicate a potential health
      risk in these workers.

PMID- 16419611
TI  - S65C and other mutations in the haemochromatosis gene in the Czech population.
AB  - HFE-linked hereditary haemochromatosis is a common autosomal recessive disease
      among Caucasians. The primary pathogenetic mechanism is excessive absorption of
      iron, which is deposited in various organs with their subsequent damage. In 1996
      the gene responsible for haemochromatosis was detected--the HFE gene and its
      major mutation C282Y. The discovery of further mutations followed. Two sites of
      point mutations in the HFE gene, C282Y and H63D, are associated with more than
      80% of haemochromatosis cases. Another mutation-- S65C--was detected on 8% of
      chromosomes of haemochromatosis patients, which were negative for mutations C282Y
      or H63D. The objective of this study was to identify the allele frequency of S65C
      and other HFE mutations in the Czech population. DNA extracted from 481 randomly
      selected newborn screening cards (Guthrie cards) from all over the country was
      analysed by PCR-RFLP. No (0%) sample was identified as homozygous for S65C or
      C282Y mutation and 8 (1.67%) were homozygous for H63D mutation. Twelve (2.49%)
      samples were S65C heterozygous, 33 (6.86%) samples were C282Y heterozygous, and
      128 (26.61%) were H63D heterozygous. Of these, 11 (2.29%) carried one copy of
      each mutation, i.e. were compound heterozygous. Two samples were S65C/H63D
      compound heterozygous and nine were C282Y/H63D compound heterozygous. Allele
      frequencies for S65C, C282Y, and H63D were 1.25% (95% CI, +/- 0.70), 3.43% (95%
      CI, +/- 1.15), and 14.97% (95% CI, +/- 2.25), respectively. The observed genotype
      frequency for S65C, C282Y, and H63D mutations in the Czech Republic agrees with
      those reported for other Central European populations.

PMID- 16419612
TI  - The use of comparative duplex PCR in monitoring of patients with non-Hodgkin's
      lymphoma and chronic lymphocytic leukaemia.
AB  - Various quantitative PCR approaches have been utilized during the last years to
      provide information about the treatment efficacy and the risk of recurrent
      disease in haematological malignancies. Apart from the frequently used real-time
      PCR, cost-saving modified standard PCR methods may be applied as well. This
      report evaluates the utility of the end-point comparative duplex PCR. We have
      used this method for monitoring of 35 patients with either NHL or CLL and
      observed a good correlation between quantitative molecular results and clinical
      outcome. There was also an agreement between comparative duplex PCR and real-time
      PCR in patients who were monitored by both methods. We therefore believe that use
      of this technique should be strongly considered instead of simple qualitative
      detection in monitoring of therapeutic outcome in NHL or CLL patients.

PMID- 16419613
TI  - Stem cell plasticity and issues of stem cell therapy.
AB  - Today, there is much evidence suggesting that organ-specific stem cells need not
      rely completely on their own sources for maintenance and regeneration of an
      organism. In certain circumstances, mostly related to tissue damage, stem cell
      populations residing past the affected organ can contribute to its recovery--that
      means from different cell lines and also in tissues from another germ layer. The
      key factor in formation of self-renewing cellular clones is the presence of stem
      cells either from the tissue of origin or stem cells migrating from other areas
      and their successful settlement in an empty niche of the damaged tissue. Stem
      cell plasticity is the ability of adult tissue-specific stem cells to switch to
      new identities. The term plasticity also means stem cell phenotypic potential,
      which is broader than phenotypes of differentiated cells in their original
      tissues. Many laboratories have given evidence on stem cell plasticity; however,
      the presented results met with many objections from others. In the first part of
      our report we wish to refer to several issues associated with stem cell
      plasticity, transdifferentiation and fusion. Recent experimental results show
      that stem cells will play a key role in cell therapy. But there are still many
      questions to answer for scientists engaged in stem cell research. Is it possible
      to induce cells from one type of tissue to look and act as cells of another
      tissue? Do these changes occur naturally? Could plasticity be used in the
      treatment of fatal diseases? Cell therapy is one of the methods to treat damaged
      myocardial tissue. However, recent results with autologous bone marrow cells in
      the treatment of damaged myocardium show that this method has still many
      unanswered questions concerning cells, cytokines, microenvironment and other
      factors responsible for reparation. To date, there are many opinions either
      recommending or denying this method in different modifications. One question has
      not yet been definitely solved: What are the conditions for us to accept this
      method--its safety and efficacy? The future will show whether these our hopes and
      expectations will be fulfiled. Many experiments are needed before at least some
      of these questions may be answered and cell therapy become an important method
      for the benefit of our patients.

PMID- 16419614
TI  - Toll-like receptors. II. Distribution and pathways involved in TLR signalling.
AB  - The innate immune system senses invading microorganisms by a phylogenetically
      conserved family of proteins--TLRs. They are expressed in several types of cells
      that represent a route of entry of pathogens into the host organism and that can
      contribute to protection against infection. Except for cells of the immune
      system, TLRs are present in epithelial cells of the skin, respiratory,
      intestinal, and genitourinary tracts that form the first protective barrier to
      invading pathogens. Polarized regulation of TLR expression in epithelial cells
      explains why pathogenic but not commensal bacteria elicit inflammatory responses.
      TLR-induced intracellular signalling pathways show remarkable complexity: apart
      from a common signalling pathway, additional signalling pathways specific for
      each of the TLRs are responsible for a fine tuning of the immune response, thus
      securing effective pathogen-directed biological responses.

PMID- 16419615
TI  - Toll-like receptors. III. Biological significance and impact for human medicine.
AB  - The ability of the innate immune system to recognize and respond to microbial
      components has been largely attributed to the family of TLRs. They are able to
      discriminate among distinct molecular patterns associated with microbial
      components. Recognition of microbial products by TLRs results in induction of
      innate immunity mechanisms as well in development of antigen-specific adaptive
      immune responses. Some of TLR ligands start to be used to enhance immune defence
      mechanisms in fighting infections or malignancies. On the contrary, others were
      shown to be involved in immunopathogenesis of autoimmune disorders such as SLE.

PMID- 16419617
TI  - Nanotechnology and potential of microorganisms.
AB  - There is a growing need to develop clean, nontoxic and environmentally friendly
      ("green chemistry") procedures for synthesis and assembly of nanoparticles. The
      use of biological organisms in this area is rapidly gaining importance due to its
      growing success and ease of formation of nanoparticles. Presently, the potential
      of bio-organisms ranges from simple prokaryotic bacterial cells to eukaryotic
      fungus and even live plants. In this article we have reviewed some of these
      biological systems, which have revolutionized the art of nano-material synthesis.

PMID- 16419616
TI  - Proteomics: a paradigm shift.
AB  - Proteome--the protein complement of a genome--has become the protein renaissance
      and a key research tool in the post-genomic era. The basic technology involves
      the routine usage of gel electrophoresis and spectrometry procedures for
      deciphering the primary protein sequence/structure as well as knowing certain
      unique post-translational modifications that a particular protein has undergone
      to perform a specific function in the cell. However, the recent advancements in
      protein analysis have ushered this science to provide deeper, bigger and more
      valuable perspectives regarding performance of subtle protein-protein
      interactions. Applications of this branch of molecular biology are as vast as the
      subject is and include clinical diagnostics, pharmaceutical and biotechnological
      industries. The 21st century hails the use of products, procedures and
      advancements of this science as finer touches required for the grooming of fast
      paced technology.

PMID- 16419619
TI  - Application of supercritical fluid extraction in biotechnology.
AB  - In the present paper recent investigations on the applications of supercritical
      fluid extraction (SCE) from post fermentation biomass or in situ extraction of
      inhibitory fermentation products as a promising method for increasing the yield
      of extraction have been reviewed. Although supercritical CO2 (SC-CO2) is
      unfriendly, or even toxic, for some living cells and precludes direct
      fermentation in dense CO2, it does not rule out other useful applications for in
      situ extraction of inhibitory fermentation products and fractional extraction of
      biomass constituents. This technique is a highly desirable method for fractional
      extraction of biomass constituents, and intracellular metabolites due to the
      potential of system modification by physical parameters and addition of co
      solvents to selectively extract compounds of different polarity, volatility and
      hydrophilicity without any contamination.

PMID- 16419618
TI  - Natural and modified (1-->3)-beta-D-glucans in health promotion and disease
      alleviation.
AB  - A number of polysaccharides with beta-glycosidic linkage are widespread in nature
      in a variety of sources. All have a common structure and the (1-->3)-beta-D
      glucan backbone is essential. They have attracted attention over the years
      because of their bioactive and medicinal properties. In many cases their
      functional role is a mystery, in others it is well established. Because of their
      insoluble chemical nature, particulate (1-->3)-beta-D-glucans are not suitable
      for many medical applications. Various methods of changing or modifying the beta
      D-glucan chemical structure and transforming it to a soluble form have been
      published. The beta-D-glucan bioactive properties can be affected positively or
      negatively by such modifications. This review examines beta-glucan sources in
      nature, health effects and structure-activity relationships. It presents the
      current state of beta-D-glucan solubilization methods and discusses their
      effectiveness and application possibilities for the future.

PMID- 16419620
TI  - A review of plastic waste biodegradation.
AB  - With more and more plastics being employed in human lives and increasing pressure
      being placed on capacities available for plastic waste disposal, the need for
      biodegradable plastics and biodegradation of plastic wastes has assumed
      increasing importance in the last few years. This review looks at the
      technological advancement made in the development of more easily biodegradable
      plastics and the biodegradation of conventional plastics by microorganisms.
      Additives, such as pro-oxidants and starch, are applied in synthetic materials to
      modify and make plastics biodegradable. Recent research has shown that
      thermoplastics derived from polyolefins, traditionally considered resistant to
      biodegradation in ambient environment, are biodegraded following photo
      degradation and chemical degradation. Thermoset plastics, such as aliphatic
      polyester and polyester polyurethane, are easily attacked by microorganisms
      directly because of the potential hydrolytic cleavage of ester or urethane bonds
      in their structures. Some microorganisms have been isolated to utilize
      polyurethane as a sole source of carbon and nitrogen source. Aliphatic-aromatic
      copolyesters have active commercial applications because of their good mechanical
      properties and biodegradability. Reviewing published and ongoing studies on
      plastic biodegradation, this paper attempts to make conclusions on potentially
      viable methods to reduce impacts of plastic waste on the environment.

PMID- 16419621
TI  - Refusal to artificially inseminate 'unmarried' lesbian.

PMID- 16419622
TI  - 83-year-old sustained brain injury in fall from hospital bed.

PMID- 16419623
TI  - PA: CNA 'voluntarily quits' job without cause: application for unemployment
      benefits denied.

PMID- 16419624
TI  - License suspension of professor fired for sexual harassment.

PMID- 16419625
TI  - Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD
      Vulvar Oncology Subcommittee.
AB  - In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is
      categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is
      neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic
      continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes
      2 types of lesion, which differ in morphology, biology and clinical features.
      VIN, usual type (warty, basaloid and mixed), is HPV related in most cases.
      Invasive squamous carcinomas of warty or basaloid type is associated with VIN,
      usual type. VIN, differentiated type, is seen particularly in older women with
      lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN,
      differentiated type, nor associated keratinizing squamous cell carcinoma is HPV
      related. The term VIN should apply only to histologically high grade squamous
      lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1
      will no longer be used. Two categories should describe squamous VIN: VIN, usual
      type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and
      VIN, differentiated type (VIN 3, differentiated type).

PMID- 16419626
TI  - Pregnancy weight gain and premenopausal breast cancer risk.
AB  - OBJECTIVE: To investigate whether excessive weight gain during pregnancy alters a
      woman's risk of developing premenopausal breast cancer. STUDY DESIGN: We
      conducted a nested case-control study within a cohort composed of 22,610 Finnish
      women (mean age, 40; SD 6.4) who responded to a questionnaire requesting
      information on breast cancer diagnosis and on adult and pregnancy weight gain as
      part of a study of a hormone-releasing intrauterine device. One hundred fourteen
      of these women reported having been diagnosed with breast cancer, and 98 were
      eligible for analysis. Four matched controls were selected for each case (n =
      392). Mean age at the time the women were diagnosed with breast cancer was 41.3
      years (SD 5.46) and at the time they returned the questionnaire, 46.7 years (SD
      5.55). RESULTS: We found no evidence that pregnancy weight gain, unadjusted or
      adjusted for prepregnancy body weight or other covariates (educational status,
      age at menarche and first pregnancy, and family history of breast cancer), had an
      effect on breast cancer risk. However, pregnancy weight gain was linked to an
      inverse association between change in body mass index (BMI) during adult life and
      premenopausal breast cancer. Women who gained an excessive amount of weight
      during pregnancy (> 16 kg) were at a significantly reduced risk of developing
      premenopausal breast cancer (p = 0.043, OR 0.28, 95% CI 0.08-0.96) if their BMI
      increased > 7 m/kg(-2) after age 20. BMI increase was not associated with breast
      cancer risk in women whose pregnancy weight gain remained within the recommended
      range (< 16 kg). CONCLUSION: Since our previous findings show that women who gain
      an excessive amount of weight during pregnancy are at an increased breast cancer
      risk after menopause, regardless of adult BMI, an excessive pregnancy weight gain
      may provide a short-term protective but cause a long-term breast cancer-promoting
      effect. It remains to be determined why BMI and pregnancy weight gain differently
      affect premenopausal and postmenopausal breast cancer risk.

PMID- 16419627
TI  - Increasing amniotic fluid magnesium concentrations with stable maternal serum
      levels: a prospective clinical trial.
AB  - OBJECTIVE: To compare the effect of prolonged maternal intravenous MgSO4
      administration on amniotic fluid and serum concentrations of magnesium over time
      in preterm labor patients. STUDY DESIGN: Patients at 24-34 weeks of singleton
      gestation who presented with contractions (> 8 in 60 minutes) underwent
      amniocentesis to rule out intrauterine infection after signing an informed
      consent form. Some of these women who were clinically judged to have preterm
      labor received intravenous MgSO4: a 4-g loading dose followed by a 2 g/h
      maintenance dose. For technical reasons some patients had amniocentesis performed
      before initiation of MgSO4 (controls), while others had the procedure during
      tocolytic therapy (study subjects). Duration of treatment until amniocentesis was
      recorded, and blood samples were drawn at the time of amniocentesis. Maternal
      serum and amniotic fluid magnesium levels were measured using a colorimetric end
      point method. Data were evaluated using the Student t test and linear regression
      analysis. RESULTS: Mean magnesium levels in maternal serum rose from 1.74 +/- 0.2
      mg/dL in controls to 4.01 +/- 0.4 mg/dL in the study group. Mean magnesium levels
      in Mean magnesium levels in amniotic fluid were 1.41 +/- 0.18 mg/dL in the
      controls versus 2.28 +/- 0.53 mg/dL in the treatment group. Duration of MgSO4
      treatment ranged from 3 to 22 hours. Amniotic fluid magnesium concentrations
      increased significantly during therapy (correlation coefficient = 0.89; p <
      0.001), while maternal serum levels remained stable over time (correlation
      coefficient between maternal serum levels and time = -0.39; p=0.34). CONCLUSION:
      Although maternal serum magnesium levels remained stable with intravenous MgSO4
      therapy, concentrations continued to rise in amniotic fluid over time. However,
      amniotic fluid magnesium levels never exceeded maternal serum concentrations
      during the study period.

PMID- 16419628
TI  - Former-resident self-assessment: a tool for residency program curriculum
      evaluation in obstetrics and gynecology.
AB  - OBJECTIVE: To determine recent residents' confidence in managing problems in
      obstetrics and gynecology. STUDY DESIGN: All former residents from 1998 to 2002
      were invited to participate. They were asked to complete a 32-item survey to
      assess confidence in obstetric and gynecologic care using Likert-scale responses.
      The study was approved by the local institutional review board. The t test was
      used for statistical analysis; p<0.05 was considered significant. RESULTS: Twenty
      eight individuals graduated from the program during the study period; 61%
      responded to the survey. Respondents reported the lowest confidence in the
      business aspects of medicine, gynecologic ultrasound, laparoscopically assisted
      hysterectomy, pessary placement and cancer staging. They reported the highest
      confidence in routine obstetrics, laparoscopic sterilization, contraception,
      abnormal Pap smears, abdominal surgery and diagnostic laparoscopy, along with
      other categories. CONCLUSION: Residents are confident about management of most
      problems in obstetrics and gynecology. Periodic review of graduates' perceptions
      of training may be useful in modifying the curriculum.

PMID- 16419629
TI  - Maximal urethral closure pressure < 20 cm H2O: does it predict intrinsic
      sphincteric deficiency?
AB  - OBJECTIVE: To assess whether the large discrepancy in the literature in the
      incidence of intrinsic sphincteric deficiency (ISD) is due to different methods
      by which maximal urethral closure pressure (MUCP) is measured. STUDY DESIGN: We
      compared the measurement of MUCP in the supine position with 300 mL saline in the
      bladder, according to International Continence Society guidelines, to that in the
      sitting position (full bladder) in 54 consecutive patients who were diagnosed as
      having stress urinary incontinence. RESULTS: In the supine position the mean MUCP
      was 38.4 +/- 2.85 cm H2O as compared to 22.80 +/- 3.22 cm H2O in the sitting
      position (p < 0.0001). The mean difference was 15.65 +/- 2.11 cm H2O. MUCP < or =
      20 cm H2O was observed in 14 of 54 (25.9%) patients in the sitting position as
      compared to 1 of 54 (1.8%) in the supine position. CONCLUSION: When MUCP is
      measured in the supine position, according to International Continence Society
      guidelines, the cutoff point for diagnosis of ISD should be 35 rather than 20 cm
      H2O.

PMID- 16419630
TI  - Expression of lysyl oxidase and transforming growth factor beta2 in women with
      severe pelvic organ prolapse.
AB  - OBJECTIVE: To determine the mRNA expression of lysyl oxidase (LOX) and
      transforming growth factor beta2 (TGF beta2) in subjects with advanced pelvic
      organ prolapse as compared to asymptomatic controls. STUDY DESIGN: Seventeen
      women undergoing vaginal hysterectomy were recruited for the study. Nine women
      with grade > or = 3 pelvic organ prolapse by the Baden-Walker grading scale were
      recruited. Eight subjects without pelvic organ prolapse or urinary incontinence
      undergoing hysterectomy for other indications were recruited as asymptomatic
      controls. A 1-cm portion of the bilateral distal uterosacral ligaments was
      excised and immediately frozen at -80 degrees C. Total RNA was extracted,
      quantified and subjected to reverse transcription for cDNA synthesis. beta-Actin
      was used as the reference for the semiquantitative analysis. Known volumes of the
      polymerase chain reaction (PCR) products for each reaction were electrophoresed
      in agarose gels stained with ethidium bromide and photographed with a digital
      camera. The optical density for each sample was measured by using computerized
      image analysis software. The relative abundance of each specific message was
      calculated as the ratio of PCR product for LOX or TGF beta2 divided by the amount
      of PCR product for beta-actin from the same sample. RESULTS: The mean age of the
      study subjects was 55.7 years (38-67) versus 47.1 for the controls (44-54). Mean
      parity was 4.4 for the study subjects and 2.7 for the controls. Seventy-eight
      percent of the study subjects were postmenopausal, and 14% of the controls
      postmenopausal. All postmenopausal subjects had at least 1 month of estrogen
      therapy prior to surgery. The mean LOX/beta-actin ratio for the study group was
      0.35 as compared to 0.72 for the control group. This was statistically
      significant with a p value of 0.049. The mean TGF beta2/beta-actin ratio for the
      study group was 0.12 as compared to 0.20 for the control group. This was not
      statistically significant (p = 0.46). CONCLUSION: Patients with severe pelvic
      organ prolapse (grade > or = 3) have a significant reduction in the mRNA
      expression of lysyl oxidase as compared to asymptomatic controls. The mRNA
      expression of TGF beta2 was not statistically different between the 2 groups.
      These findings lend further credence to the concept of specific biochemical
      changes in the pelvic floor in women with pelvic organ prolapse.

PMID- 16419631
TI  - Obstetric characteristics and neonatal outcome of unplanned out-of-hospital term
      deliveries: a prospective, case-control study.
AB  - OBJECTIVE: To describe the obstetric characteristics and neonatal outcomes in
      unplanned out-of-hospital deliveries. STUDY DESIGN: Obstetric characteristics and
      neonatal outcomes were compared between 151 consecutive parturients with
      unplanned, out-of-hospital term deliveries and 151 hospital term deliveries.
      RESULTS: Women who delivered out of hospital tended to be older (32 +/- 5.5 vs.
      28 +/- 5.0 years, p = 0.046) and less educated (4.4 +/- 5.1 vs. 6.5 +/- 5.0
      years, p = 0.005) as compared to women who delivered in the hospital. Unplanned
      out-of-hospital deliveries resulted in statistically significant higher rate of
      low-birth-weight newborns (< 2,500 g) (OR= 3.9, 95% CI 2.0-7.7, p<0.001),
      postpartum hemorrhage (OR = 8.4, 95% CI 1.1-181.1, p = 0.018) and trended for
      higher rate of manual lysis of retained placenta and membranes (4.0% vs. 0%, p =
      0.013). Higher rates of admission to the neonatal intensive care unit due to
      neonatal complications, such as polycythemia (12.6% vs. 0%, p < 0.001),
      hypoglycemia (9.3% vs. 0.6%, p = 0.001) and convulsions (3.3% vs. 0%, p = 0.024),
      were noted in the out-of-hospital delivery group as compared to the controls.
      Using a multivariable analysis, lower educational level (OR = 0.4, 95% CI 0.3
      0.4, p < 0.001), maternal age > 35 (OR = 6.2, 95% CI 2.3-16.7, p < 0.001) and
      high parity (OR = 7.9, 95% CI 4.9-12.9, p<0.001) were found to be independent
      risk factors for an unplanned outof hospital delivery. CONCLUSION: Unplanned out
      of-hospital birth is an important risk factor for such complications as
      postpartum hemorrhage, low birth weight and adverse neonatal outcome.

PMID- 16419632
TI  - Uterine effect of cervical buffeting: role of the cervicouterine reflex in
      coitus.
AB  - OBJECTIVE: To investigate the hypothesis that cervical buffeting during coitus
      effects reflex relaxation and dilatation of the corpus uteri (CorU) smooth
      muscle; that mechanism acts to suck the ejected semen into the CorU. STUDY
      DESIGN: The CorU response to electrical and mechanical stimulation of the CU was
      recorded in 22 healthy women (mean age, 38.2 +/- 7.6 SD years). Cervical
      electrical stimulation was effected by an electromyographic needle electrode and
      mechanical stimulation by pencil electrode. The test was repeated after
      individual anesthetization of the CU and CorU and after normal saline injection.
      RESULTS: Slow waves, superimposed or followed by action potentials, were recorded
      at rest from the CorU electrode. Electrical or mechanical stimulation of the CU
      effected a significant reduction of the electric wave parameters and pressure in
      the CorU; this response was reproducible. Separate stimulation of the
      anesthetized CU or CorU did not evoke the response, while saline infiltration
      did. CONCLUSION: CU stimulation resulted in diminished CorU electrical activity
      and pressure; that presumably indicates uterine wall relaxation. Repeated CU
      buffeting apparently leads to an intermittent uterine pressure decline, with
      resulting semen siphonage from the vagina to the uterus. Diminished CorU
      electrical activity and pressure on cervical stimulation or buffeting might be
      mediated through the cervicouterine inhibitory reflex. This reflex seems to be
      evoked by penile thrusting during coitus and may prove of diagnostic significance
      in sexual disorders.

PMID- 16419633
TI  - Uterine artery embolization in the management of vaginal bleeding from cervical
      pregnancy: a case series.
AB  - OBJECTIVE: To report our experience of selective embolotherapy in 8 consecutive
      patients with cervical pregnancy (CxP) presenting with vaginal bleeding. STUDY
      DESIGN: A total of 9 selective pelvic embolization procedures were performed on 8
      patients with CxP, either as an emergency, for control of vaginal hemorrhage (2
      patients), or on a nonemergency basis, for moderate vaginal bleeding (6
      patients). One patient underwent 2 embolization procedures, once for each
      indication. RESULTS: Successful hemostasis was obtained in both emergency cases.
      In 3 of the nonemergency cases, the CxP rapidly resolved. In the 3 other
      nonemergency cases, elevated beta-human chorionic gonadotropin levels persisted,
      with a new episode of vaginal bleeding in 2 patients 2 and 4 weeks later,
      respectively; the bleeding resolved after the administration of methotrexate.
      Significant vaginal hemorrhage occurred 4 weeks later in the third patient and
      responded to repeat embolotherapy. One patient required a blood transfusion. The
      uterus was preserved in all 8 patients. One patient was lost to follow-up, but
      normal menses resumed in all 7 of the others; and 2 patients had subsequent
      successful pregnancies. CONCLUSION: Embolotherapy is effective in treating and
      preventing vaginal hemorrhage associated with CxP while allowing uterine
      preservation. Along with methotrexate and other medical treatment of CxP, we
      recommend routine use of embolization in patients presenting with vaginal
      bleeding.

PMID- 16419634
TI  - Clinical utility of fetal fibronectin for predicting preterm birth.
AB  - OBJECTIVE: To determine if fetal fibronectin can be used in a clinical setting to
      predict preterm birth and guide clinical management. STUDY DESIGN: We implemented
      a clinical protocol using the rapid fetal fibronectin test for patients
      presenting with symptoms of preterm labor. Adherence to the clinical pathway was
      at the discretion of the practitioner. Subjects who met the inclusion criteria (n
      = 404) were divided into 2 groups based on the fetal fibronectin result. Outcomes
      included time until delivery, gestational age at delivery and use of therapeutic
      interventions. Univariate and multivariate statistical analyses were performed.
      RESULTS: The 46 subjects (11.4%) with positive fetal fibronectin were more likely
      to deliver within 7 days, within 14 days, prior to 32 weeks' gestation and prior
      to 37 weeks' gestation (RR 22.0, 22.0, 12.3 and 5.1, respectively). For delivery
      within 7 days, the sensitivity, specificity, positive predictive value and
      negative predictive value were 67%, 92%, 30% and 98%, respectively. Time until
      delivery and gestational age at delivery were lower in women with a positive
      test, while the frequency of therapeutic interventions was higher (p < 0.01).
      CONCLUSION: A positive fetal fibronectin test is predictive of preterm birth in a
      clinical setting. A negative fetal fibronectin test can be used to avoid
      unnecessary, potentially harmful interventions.

PMID- 16419635
TI  - Ilioinguinal/iliohypogastric neurectomy for management of intractable right lower
      quadrant pain after cesarean section: a case report.
AB  - BACKGROUND: Ilioinguinal nerve entrapment is one of the most common nerve
      injuries following pelvic surgery. We present a case of intractable right lower
      quadrant pain successfully treated with neurectomy. CASE: A 31-year-old woman,
      following her third elective cesarean section, noted intense, right inguinal pain
      immediately upon awaking from anesthesia. The pain was burning and constant and
      exacerbated by standing and movement. After a period of failed conservative
      management, a workup concluded probable nerve entrapment. Trigger point
      injections, amitriptyline and gabapentin therapy resulted in minimal improvement.
      At 10 months the patient underwent a right ilioinguinal neurectomy with excellent
      sustained pain relief. CONCLUSION: Low transverse fascial incisions risk injury
      to the iliohypogastric and ilioinguinal nerves. While pain from entrapment of
      these nerves often resolves spontaneously, neurectomy may offer resolution in
      recalcitrant cases.

PMID- 16419636
TI  - Well-differentiated papillary mesothelioma of the uterine serosa identified at
      cesarean section: a case report.
AB  - BACKGROUND: Peritoneal mesotheliomas encompass a variety of benign and malignant
      neoplasms. Well-differentiated papillary mesothelioma (WDPM) is uncommon, is
      thought to be of low malignant potential and is often discovered incidentally
      during abdominal or pelvic surgery. We describe a highly unusual case in which
      WDPM arising from the uterine serosa was identified at the time of cesarean
      delivery. CASE: A 21-year-old primigravida underwent cesarean delivery at term
      for arrest of the active phase of labor. A 2-cm, polypoid lesion was excised from
      the posterior uterine fundus; final pathology showed well-differentiated
      papillary mesothelioma. Subsequent examination and computed tomography were
      negative. A follow-up laparoscopic examination with abdominal washing for
      cytology and peritoneal biopsies revealed no residual disease. CONCLUSION: Survey
      of the pelvic cavity during cesarean section is important. Knowledge of the
      variable disease spectrum of mesothelioma is important in patient counseling and
      management. Differentiating between WDPM and malignant mesothelioma, other
      peritoneal tumors and implants from primary sites is necessary to avoid
      overtreatment.

PMID- 16419637
TI  - Recombinant human erythropoietin in a triplet pregnancy: a case report.
AB  - BACKGROUND: Women carrying triplets are at greater risk for both anemia, due to
      the increased demands of the developingfetuses, and peripartum hemorrhage.
      Jehovah's witnesses are a unique obstetric population since women of this faith
      refuse blood transfusion. CASE: A Jehovah's Witness with a triplet pregnancy was
      successfully administered recombinant human erythropoietin (rHuEpo), 200 IU/kg 3
      times per week subcutaneously, in order to correct her peripartum anemia. No side
      effects were observed during rHuEpo therapy, and the patient delivered healthy
      triplets. CONCLUSION: rHuEpo can be safely administered, with a beneficial effect
      in pregnancy, and seems to be an effective option in preventing transfusions as
      demonstrated in this case in a Jehovah's Witness.

PMID- 16419638
TI  - Melanosis of the uterine cervix: a case report.
AB  - BACKGROUND: Melanosis of the uterine cervix is a rare, benign, melanocytic lesion
      of the cervix. A review of the English-language literature revealed 11 other
      reported cases. CASE: A 52-year-old African American woman who presented for
      evaluation and treatment of menorrhagia was found to have an irregular, pigmented
      cervical lesion. The ectocervical biopsy showed melanosis characterized by
      hyperkeratosis, acanthosis and prominent elongation of rete with abundant basilar
      pigmentation. Immunohistochemical staining showed scattered, basally situated, S
      100 protein-positive melanocytes. CONCLUSION: The existence of this entity is
      further evidence of a spectrum of melanocytic lesions, including blue nevi and
      primary melanomas, known to occur within the cervix proper.

PMID- 16419639
TI  - Ovarian endometrioma complicated by a Salmonella abscess caused by an
      enteroovarian fistula: a case report.
AB  - BACKGROUND: Salmonella infection occurs primarily in the gastrointestinal tract
      but may also be found at extraintestinal locations. An ovarian abscess caused by
      Salmonella is one of the rare extraintestinal infections, and hematogenous spread
      by bacteremia to a preexisting ovarian cyst has been suggested as the cause of
      such infections. CASE: A 43-year-old woman presented with diarrhea, fever and an
      ovarian tumor and was treated initially with antibiotics for Salmonella
      bacteremia, followed by an exploratory laparotomy due to persistent fever and
      progressive toxic signs. A pus-containing endometrioma with a thick wall densely
      adhering to an intestinal segment, with a fistula connecting the 2, was found
      during surgery. The patient underwent a salpingo-oophorectomy and resection of
      the intestinal segment, took antibiotics and recovered. Bacterial culture of the
      abscess showed salmonellosis, and pathology reported a fistula between the
      ovarian tumor and intestine, suggesting that direct spread through a fistula may
      be one of the causes of extraintestinal Salmonella infections. CONCLUSION:
      Salmonella infection located in the ovary is a rare condition, often caused by
      bacteremia. To the best of our knowledge, this is the first report of an ovarian
      Salmonella abscess that occurred through a fistula.

PMID- 16419640
TI  - Combined bladder, urethral and uterine rupture after a normal, spontaneous
      vaginal delivery at home: a case report.
AB  - BACKGROUND: Uterine rupture and associated injury to the maternal bladder and
      urethra have been rarely reported. All those cases were associated with a scarred
      uterus or augmentation of labor. We report a case of simultaneous bladder,
      urethral and uterine rupture in an unscarred uterus following delivery at home.
      CASE: A 22-year-old woman was referred from a peripheral hospital to the
      emergency unit of the Medical Faculty, Yuzuncu Yil University, after delivering
      at home. On vaginal examination, the bladder neck and proximal one third of the
      urethra were ruptured. Intraoperatively it appeared that the posterior wall of
      the bladder and bladder base had ruptured and separated from the level of the
      interureteric ridge. An extensive rupture of the lower uterine segment to the
      left sidewall of the uterus was seen. CONCLUSION: To prevent these complications,
      uneducated, traditional birth attendants should be replaced by at least midwives,
      and the rate of unsupervised home delivery should be reduced.

PMID- 16419641
TI  - The role of tumor necrosis factor-alpha in inducing insulin resistance in the
      renin-angiotensin system.

PMID- 16419642
TI  - A novel missense mutation, F826Y, in the mineralocorticoid receptor gene in
      Japanese hypertensives: its implications for clinical phenotypes.
AB  - A gain-of-function mutation resulting in the S810L amino acid substitution in the
      hormone-binding domain of the mineralocorticoid receptor (MR, locus symbol NR3C2)
      is responsible for early-onset hypertension that is exacerbated in pregnancy. The
      objective of this study was to test whether other types of missense mutations in
      the hormone-binding domain could be implicated in hypertension in Japanese. Here,
      we screened 942 Japanese patients with hypertension for the S810L mutation in
      exon 6 in the MR. We did not identify the S810L mutation in our hypertensive
      population, indicating that S810L does not play a major role in the etiology of
      essential hypertension in Japanese. However, we identified a novel missense
      mutation, F826Y, in three patients in a heterozygous state, in addition to four
      single nucleotide polymorphisms, including one synonymous mutation (L809L). The
      F826Y mutation is present in the MR hormone-binding domain and might affect the
      ligand affinity. The F826Y mutation was also identified in 13 individuals (5
      hypertensives and 8 normotensives) in a Japanese general population (n=3,655).
      The allele frequency was 0.00178. The frequencies of the F826Y mutation in the
      hypertensive population (3/942) and in the hypertensive group (5/ 1,480) and the
      normotensive group (8/2,175) in the general population were not significantly
      different, suggesting that this mutation does not greatly affect hypertension.
      Although it is unclear at present whether or not the F826Y mutation makes a
      substantial contribution to the mineralocorticoid receptor activity, this
      missense mutation may contribute, to some extent, to clinical phenotypes through
      its effects on MR.

PMID- 16419643
TI  - Antihypertensive effect of green coffee bean extract on mildly hypertensive
      subjects.
AB  - A water-soluble green coffee bean extract (GCE) has been shown to be effective
      against hypertension in both spontaneously hypertensive rats and humans. This
      multicenter, randomized, double-blind, placebo-controlled, parallel group study
      evaluated the dose-response relationship of GCE in 117 male volunteers with mild
      hypertension. Subjects were randomized into four groups: a placebo and three drug
      groups that received 46 mg, 93 mg, or 185 mg of GCE once a day. After 28 days,
      systolic blood pressure (SBP) in the placebo, 46 mg, 93 mg, and 185 mg groups was
      reduced by -1.3+/-3.0 mmHg, -3.2+/-4.6 mmHg, -4.7+/-4.5 mmHg, and -5.6+/-4.2 mmHg
      from the baseline, respectively. The decreases in SBP in the 93 mg group (p<0.05)
      and the 185 mg group (p<0.01) were statistically significant compared with the
      placebo group. Diastolic blood pressure (DBP) in the placebo, 46 mg, 93 mg, and
      185 mg groups was reduced by -0.8+/-3.1 mmHg, -2.9+/-2.9 mmHg, -3.2+/-3.2 mmHg,
      and -3.9+/-2.8 mmHg from the baseline, respectively, and significant effects were
      observed in the 93 mg group (p<0.05) and the 185 mg group (p<0.01) compared with
      the placebo group. Both blood pressures were significantly reduced in a dose
      related manner by GCE (p<0.001). Adverse effects caused by GCE were not observed.
      The results suggested that daily use of GCE has a blood pressure-lowering effect
      in patients with mild hypertension.

PMID- 16419644
TI  - A single nucleotide polymorphism in the carboxylesterase gene is associated with
      the responsiveness to imidapril medication and the promoter activity.
AB  - Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in
      treating hypertension, although the responses vary among individuals. We
      investigated whether a single nucleotide polymorphism at position -816 of the
      carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is
      involved in the responsiveness to imidapril medication. A total of 105 Japanese
      hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140/90 mmHg or
      higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure
      levels were not different between patients with and those without the -816C
      allele (AA vs. AC+ CC groups). After 8 weeks of treatment, we classified the
      responders and non-responders based on the decline in their blood pressures, and
      found that the responder rate was significantly higher in the AC+CC group than in
      the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in
      the AC+CC group than in the AA group (24.7+/-11.8 vs. 17.6+/-16.8 mmHg,
      p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C
      construct had significantly higher promoter activity (p<0.0001). These findings
      suggest that the A(-816)C polymorphism affects the transcriptional activity, and
      that this may account for the responsiveness to imidapril.

PMID- 16419645
TI  - Establishing reference values for both total soluble Fms-like tyrosine kinase 1
      and free placental growth factor in pregnant women.
AB  - It has been reported that the concentration of free placental growth factor
      (PIGF) is decreased and that of soluble fms-like tyrosine kinase 1 (sFlt-1) is
      increased before the onset of preeclampsia. However, no study has determined the
      reference values for sFlt-1 and free PIGF during pregnancy using a commercially
      available enzyme-linked immunosorbent assay (ELISA) kit. This longitudinal cohort
      study was undertaken to address this issue. Serum samples were collected from 148
      women at 10, 18, 28, and 37 weeks of gestation. Preeclampsia occurred in 6 women:
      4 women who delivered at <37 weeks of gestation, and 2 women who delivered at >
      or =37 weeks. The average and 90% confidence interval (90% CI) of the serum
      concentration of both sFIt-1 and free PIGF were determined in a total of 433
      specimens from 148 subjects with 1 to 4 collections at 7 to 39 weeks of
      gestation, and were represented as quadric curves. The mean values (90% CI) of
      sFlt-1 (pg/ml) at 10, 18, 28, and 37 weeks of gestation were 413 (174-981), 296
      (125-704), 413 (174-982), and 1,130 (477-2,690), respectively. The mean values
      (90% CI) of free PIGF (pg/ml) were 36 (14-89), 206 (83-515), 518 (207-1,290), and
      354 (142-884), respectively. We also established the reference values for the
      ratio of sFlt-1/PIGF. These values may be useful for predicting the subsequent
      occurrence of preeclampsia.

PMID- 16419646
TI  - Long-term renoprotective effect of combination therapy with prostaglandin E1 and
      angiotensin-converting enzyme inhibitor in patients with chronic renal failure.
AB  - Angiotensin-converting enzyme inhibitors (ACE-I) have a renoprotective effect in
      patients with chronic renal failure. Prostaglandins (PGs) have also been shown to
      ameliorate renal impairment. Although these two have different mechanisms-ACE-I
      reduces intraglomerular pressure by dilating the efferent arterioles, while it is
      thought that PGs may increase intraglomerular pressure--coadministration of these
      drugs may have an additive effect. Administration of a PG with an ACE-I might
      have an additive effect on chronic renal failure. However, there have been no
      studies on the efficacy of such a combination therapy. This study was conducted
      to determine whether combination therapy with PGE1 and an ACE-I might have a long
      term benefit on chronic renal failure. Sixty patients with chronic renal disease
      receiving an ACE-I in advance were assigned to receive an ACE-I alone or an ACE-I
      plus PGE1. Blood pressure, blood chemistry, urinary protein excretion, and the
      changes in the reciprocal of serum creatinine (delta1/Cr) were monitored once
      monthly for an average of 36.5 months. In patients treated only with an ACE-I,
      the progression of renal failure did not change with time. In contrast, the
      decline of renal function was significantly reduced with the combination therapy.
      The renoprotective effect of the combination therapy was not exerted by reduced
      proteinuria or by decreased blood pressure. PGE1 may reinforce the renoprotective
      effects of ACE-I to prevent the progression of chronic renal failure.

PMID- 16419647
TI  - Hypotension associated with prone body position: a possible overlooked postural
      hypotension.
AB  - Conditions related to the dysregulation of blood pressure (BP), such as
      orthostatic hypotension, have been shown to be significantly associated with
      cardiovascular disease. Recently, the prone body position has been recognized as
      a possible postural factor leading to BP dysregulation. We conducted a cross
      sectional study to investigate the BP response to a change in body position from
      supine to prone. The study subjects consisted of 271 middle-aged healthy males,
      randomly selected from the employees of a large manufacturing enterprise in Ehime
      Prefecture, Japan. Brachial BP and heart rate were measured in a sitting, supine
      and prone position, in that order, and each difference was defined as a postural
      change. The postural changes in aortic hemodynamics were also assessed using a
      SphygmoCor system. The basal BP measured in the sitting position was
      significantly decreased in the supine position (132+/-18 to 130+/-17 mmHg,
      p<0.001). A further reduction was observed after the postural change from supine
      to prone (130+/-17 to 125+/-16 mmHg, p<0.001). The heart rate was increased with
      the supine-to-prone postural change (4.1+/-5.8 beats/min, p<0.001), while it
      showed a significant decrease with the sitting-to-supine postural change (-7.6+/
      5.6 beats/ min, p<0.05). The impact of BP reduction was more prominent in the
      aortic artery (-3.3+/-6.7%) than the brachial artery (-3.0+/-6.3%, p=0.020).
      Multiple regression analysis showed that basal systolic BP was a solely
      significant determinant of the prone-hypotension (beta=-0.309, p<0.001). In
      conclusion, these results indicate that lying in a prone posture could lead to
      unregulated postural hypotension, which has the possibility of being a novel
      predictor of cardiovascular frailty.

PMID- 16419648
TI  - Influence of leisure-time physical activity on the relationship between C
      reactive protein and hypertension in a community-based elderly population of
      Japan: the Tsurugaya project.
AB  - There are several studies indicating an association between C-reactive protein
      (CRP) and blood pressure (BP) in the Japanese population, but the influence of
      physical activity has not been considered. Therefore, we designed a cross
      sectional survey to determine whether leisure-time physical activity (LTPA)
      modifies the relation between CRP and hypertension among Japanese elderly. Our
      study population comprised 643 subjects aged 70 years and over in whom CRP, home
      BP, and self-reported LTPA were measured. LPTA was categorized into three levels
      of intensity--walking, brisk walking, and sports-and a questionnaire was used to
      estimate the level in each patient. Hypertension was defined as a home systolic
      BP of 135 mmHg or over and/or home diastolic BP of 85 mmHg or over or current use
      of antihypertensive agents. LTPA levels were associated with both CRP and
      hypertension. After adjustment for factors affecting CRP and hypertension, and
      additional adjustment for LTPA levels, the odds ratio (95% confidence interval)
      of hypertension by CRP was 2.21 (range: 1.33-3.72), 1.99 (1.17-3.42), and 2.38
      (1.36-4.21) times higher in subjects in the second, third, and fourth quartiles
      of CRP, as compared to subjects in the first quartile, respectively. A multiple
      regression model showed a positive and significant relation between log
      transformed CRP and systolic BP after adjustment for potential confounding
      factors when participants taking antihypertensive medication were excluded. This
      is the first study to clarify that the positive significant relation between CRP
      and hypertension was independent of LTPA levels among Japanese elderly.

PMID- 16419649
TI  - Oxidative stress by peripheral blood mononuclear cells is increased in
      hypertensives with an extreme-dipper pattern and/or morning surge in blood
      pressure.
AB  - Because oxidative stress and inflammation are known to play important roles in
      the pathogenesis of cardiovascular events that occur most frequently in the
      morning, we studied the association between reactive oxygen species (ROS)
      formation by polymorphonuclear leukocytes (PMNs) or mononuclear cells (MNCs) and
      morning blood pressure (BP) rhythm. A total of 31 hypertensives in whom
      ambulatory BP monitoring was performed participated in this study. They were
      first divided into three groups according to their nocturnal BP rhythm (non
      dippers, dippers and extreme dippers), and then into two groups according to
      their morning BP change (surge-type and sustained-type). ROS formation by PMNs
      and MNCs was measured by gated flow cytometry. C-reactive protein and traditional
      risk factors such as age, gender, body mass index, hemoglobin A1c, and total
      cholesterol were also measured. ROS formation by MNCs was significantly increased
      in extreme dippers (vs. dippers, p<0.05, n=11) and in morning BP surge-type
      hypertensives (vs. sustained-type, p<0.05, n=13). In patients who were both
      extreme dippers and morning BP surge-types, ROS formation by MNCs was
      significantly higher than that in other groups. These results suggest that both
      extreme dippers and morning BP surge-type hypertensives may suffer increased ROS
      formation by MNCs, and that increased ROS formation by MNCs may underlie morning
      strokes.

PMID- 16419650
TI  - Effect of estrogen on differentiation and senescence in endothelial progenitor
      cells derived from bone marrow in spontaneously hypertensive rats.
AB  - The functional impairment associated with atherogenic factors, including
      hypertension, constitutes a limitation to the ability of endothelial progenitor
      cells (EPCs) to repair. In addition, estrogens have been shown to play a role in
      reendothelialization after vascular injury. We investigated the effects of
      estrogens on differentiation and senescence of EPCs derived from bone marrow (BM
      EPCs) in spontaneously hypertensive rats (SHR/Izm). Bone marrow (BM) cells were
      obtained from the tibias and femurs of age-matched, male SHR/Izm and Wistar-Kyoto
      rats (WKY/Izm). The number of differentiated, adherent BM-EPCs derived from
      SHR/Izm was significantly smaller than the number derived from WKY/Izm. 17beta
      Estradiol (E2) significantly increased the number of adherent BM-EPCs from
      SHR/Izm, and this effect was significantly attenuated by pharmacological
      phosphatidylinositol 3-kinase (PI3-K) blockers. Immunoblotting analysis revealed
      that E2 treatment led to phosphorylation of Akt. Senescence, as assessed by
      acidic beta-galactosidase staining, occurred at a significantly greater rate in
      the BM-EPCs from SHR/Izm than in those from WKY/Izm, but E2 treatment
      dramatically delayed the senescence of BM-EPCs from SHR/Izm. A polymerase chain
      reaction (PCR)-ELISA based assay revealed that telomerase activity in BM-EPCs
      from SHR/Izm was significantly lower than in those from WKY/Izm, but that E2
      treatment significantly augmented it. Both MTS and colony forming unit assay
      revealed that E2 treatment significantly augmented the functional activity in BM
      endothelial cell (EC)-like cells from SHR/Izm compared to that in control BM-EC
      like cells (no treatment). In conclusion, the differentiation of BM-EPCs derived
      from SHR/Izm was significantly decreased compared with that of BM-EPCs from
      WKY/Izm. In addition, the rate of senescence was significantly greater in the BM
      EPCs from SHR/Izm than in those from WKY/Izm. Estrogen was shown to augment
      differentiation and delay the onset of senescence in BM-EPCs from SHR/Izm.

PMID- 16419652
TI  - Lotus after cesarean.

PMID- 16419651
TI  - Olmesartan ameliorates insulin sensitivity by modulating tumor necrosis factor
      alpha and cyclic AMP in skeletal muscle.
AB  - We have reported that tumor necrosis factor (TNF)-alpha in skeletal muscle is one
      of the determinants of insulin resistance and that the renin-angiotensin system
      may be related to the regulation of TNF-a in skeletal muscle. Recent studies have
      suggested the involvement of cyclic adenosine monophosphate (cAMP) in the
      regulation of TNF-a in vascular smooth muscle cells or monocytes. The aim of this
      study was to determine the relationship between cAMP and TNF-a in skeletal muscle
      in connection with the renin-angiotensin system. Six-week-old male Sprague-Dawley
      rats were fed either normal rat chow or fructose-rich chow for 6 weeks. For the
      last 2 weeks of a 6-week period, the rats were treated with a vehicle or with an
      angiotensin II type 1 receptor antagonist (olmesartan medoxomil, 0.1 mg/kg/day).
      TNF-alpha levels in the soleus muscle were significantly higher and cAMP levels
      in the soleus muscle were significantly lower in fructose-fed rats than in
      control rats. Olmesartan increased cAMP and reduced TNF-a simultaneously in
      fructose-fed rats. There was a significant negative correlation between levels of
      cAMP and TNF-alpha. Moreover, a cAMP analogue reduced TNF-a levels in the soleus
      muscle. These results indicate that the increase in TNF-alpha via suppression of
      cAMP may affect the induction of insulin resistance. In addition, the facts that
      olmesartan increased cAMP and decreased TNF-alpha suggest that a part of the TNF
      alpha regulation by angiotensin II might consist of modulation of cAMP through Gi
      protein activation in skeletal muscle.

PMID- 16419653
TI  - Comments on epidural study conclusions.

PMID- 16419655
TI  - Elephant birth.

PMID- 16419654
TI  - Comments on epidural study conclusions.

PMID- 16419656
TI  - Preventable medical errors.

PMID- 16419657
TI  - Midwifery Model of Care--Phase II.

PMID- 16419658
TI  - Marion's message. Three births in posterior position.

PMID- 16419659
TI  - A decade of nurse-midwifery practice, and done.

PMID- 16419660
TI  - Just say no to drugs.

PMID- 16419661
TI  - Birth crisis.

PMID- 16419662
TI  - They do come out.

PMID- 16419663
TI  - Occiput posterior position should be exceptionally rare at birth.

PMID- 16419664
TI  - Homeopathic tools for occiput posterior position.

PMID- 16419665
TI  - An interview with Mabel Dzata. Interview by Heather Long.

PMID- 16419666
TI  - Lecithin: it isn't just for plugged milk ducts and mastitis anymore.

PMID- 16419667
TI  - Is posterior position really a problem?

PMID- 16419668
TI  - Giving birth: a midwife's faith in birth is reborn.

PMID- 16419669
TI  - Birth and death: the mystery of mortality, an interview with Jeannine Parvati
      Baker, Part two.

PMID- 16419670
TI  - Reclaiming a Cuban heritage, Nassau, Bahamas, September 2005.

PMID- 16419671
TI  - An extraordinary ordinary birth.

PMID- 16419673
TI  - A call to action: vaginal birth after cesarean (VBAC) in crisis in Florida.

PMID- 16419672
TI  - Reducing the risk of postpartum depression.

PMID- 16419674
TI  - HIV in postpartum and baby care.

PMID- 16419675
TI  - The business of midwifery: documentation for success II.

PMID- 16419676
TI  - Heavy metal toxicity and the unborn child.

PMID- 16419677
TI  - What hope looks like: a visit to the Fistula Hospital.

PMID- 16419678
TI  - Homebirth in Nigeria: obstacles and prospects.

PMID- 16419679
TI  - Mexico birth center: Part II.

PMID- 16419680
TI  - Traditional Mexican midwifery: Dona Enriqueta Contreras.

PMID- 16419681
TI  - Tinnitus neural substrates: an addendum.

PMID- 16419682
TI  - Specific findings in distortion product otoacoustic emissions and growth
      functions with chronic tinnitus.
AB  - Chronic tinnitus has a very high prevalence in industrialized countries. Latest
      studies found chronic tinnitus in 4% of the German population, with almost 2%
      suffering severely in their daily life. Because no curative therapeutic approach
      is available--neither pharmacological nor surgical--the main focus lies in
      treatments that enhance the habituation of tinnitus. Habituation occurs in almost
      50% of affected patients as a normal process, leading to a complete compensation.
      This finding is based on the ability of the auditory perception to habituate
      random noise and focus on important acoustic information. According to our
      audiological data, 90% of tinnitus patients have deficits in inner-ear function
      as a generator of tinnitus, mainly in the outer hair cells. This occurrence can
      be verified by registration of distortion products of otoacoustic emissions.
      Thus, the main origin of tinnitus is peripheral, and most patients suffer from
      accompanying hearing loss, even though it is sometimes mild or subjectively not
      even noticed. In almost 50% of our patients, we find hyperfunction of outer hair
      cells, again recorded via distortion products of otoacoustic emissions and their
      growth functions. Normal efferent reduction of distortion products through
      contralateral acoustic stimulation does not take place in most tinnitus patients.
      This finding shows that central auditory functions are also disturbed in chronic
      tinnitus patients, leading to reduced efferent effects on the hair cells and thus
      impeding habituation. Tests to verify these more central pathological findings
      have yet to be developed. We have data on diminished ability to distinguish
      stimuli from random noise by bilateral sound processing: The so-called bilateral
      masking difference test results are pathological in almost 30% of patients
      suffering from chronic tinnitus. We concluded from our audiological data that
      chronic tinnitus is primarily a cochlear dysfunction, but habituation is impeded
      by accompanying or consecutive deficits of the central auditory pathway.
      Regarding therapeutic approaches, these central functions can be trained by
      hearing therapy, as we know from patients' rehabilitation.

PMID- 16419683
TI  - Tinnitus improvement with ultra-high-frequency vibration therapy.
AB  - This study reports on the long-term benefit of ultra-high-frequency masking with
      the UltraQuiet device. A commercial product, UltraQuiet provides a new form of
      high-frequency bone conduction therapy. To assess its effectiveness in tinnitus
      treatment, we selected 15 patients with problematic tinnitus and randomly
      assigned them to three variations of the medical-audiological tinnitus patient
      protocol modified for the UltraQuiet study. We assessed tinnitus relief by
      questionnaires directed at weighing patient response to overall effectiveness,
      tinnitus loudness, tinnitus severity, and tinnitus annoyance. Additionally, we
      performed audiological measures (including pure-tone and speech audiometry,
      minimal masking levels, pitch and loudness matching, and residual inhibition).
      All patients showed some long-term gains, and most exhibited relief in at least
      one measurement parameter, providing support for the use of high-frequency
      vibration in the treatment of tinnitus.

PMID- 16419684
TI  - Neurochemistry of the peripheral and central auditory system after ototoxic drug
      exposure: implications for tinnitus.
AB  - Platinum-containing drugs, such as cisplatin and carboplatin, are known to have
      ototoxic side effects causing hearing loss that may be accompanied by tinnitus.
      This study reviews recent studies on the ototoxicity of cisplatin and carboplatin
      and summarizes the effects of protective agents that may prevent hearing loss and
      tinnitus. The primary locus of ototoxicity is in the cochlea, but oxidative
      stress to the inferior colliculus has been reported recently with carboplatin.
      Enhanced spontaneous activity within the dorsal cochlear nucleus has been
      correlated with loss of outer hair cells in animal experiments using cisplatin.
      This may result from disinhibition of neurons within the dorsal cochlear nucleus
      caused by reduced input from spiral ganglion cells. Carboplatin may cause
      tinnitus by oxidative stress within the inferior colliculus or by loss of
      inhibition within the inferior colliculus resulting from cochlear damage. This
      could lead to compensatory gain and enhanced responses in neurons within the
      auditory cortex. Protective agents may prevent tinnitus by preventing damage to
      the cochlea, thereby obviating the development of disinhibition within central
      auditory pathways.

PMID- 16419685
TI  - Round-window anatomical considerations in intratympanic drug therapy for inner
      ear diseases.
AB  - Our aim was to elucidate the importance of anatomical aspects in planning local
      therapies for inner-ear diseases. The study undertakes the anatomical evaluation,
      from a surgical-approach perspective, of the relationship between the false and
      true round-window membranes. As our design, we chose a human temporal bone
      dissection study, for which we used 20 fresh temporal bones. After an exploratory
      tympanotomy and atticotomy, we drilled the anterosuperior (promontory) edge of
      the round-window niche until the true round-window membrane was completely
      exposed. We registered the presence or absence and the extent of the false round
      window membranes on the round-window niche. We found false round-window membranes
      obstructing the round-window niche partially or completely in five temporal bones
      (25%). Complete obstruction was present in one temporal bone (5%). We found
      mucoperiosteal folds obstructing the round-window niche partially or completely
      in a significant proportion of the ears. These anatomical particularities could
      account, at least partially, for the great variability of the results of
      intratympanic therapies for inner-ear diseases.

PMID- 16419686
TI  - Topical administration of Caroverine in somatic tinnitus treatment: proof-of
      concept study.
AB  - This prospective study, which conformed with good clinical practice (GCP
      conform), tested the concept that the topical transtympanic administration of the
      quinoxaline derivative Caroverine promises a new approach to the treatment of
      tinnitus. The rationale for the study is the hypothesis that tinnitus reflects
      sequelae of auditory neurotoxicity that can prevented and repaired by the
      neuroprotective and neuroregenerative activities of quinoxaline derivatives
      exhibited in previous preclinical tests. In a representative patient cohort, the
      probability of a long-lasting tinnitolytic effect of lipophilic eardrops
      containing 1% Caroverine as their active ingredient gained in significance,
      crossing from low-intensity levels to high-intensity levels of individual
      tinnitus sensations. These results encouraged us to design consequential GCP
      conform phase 2 and phase 3 studies.

PMID- 16419687
TI  - Sodium enoxaparin treatment of sensorineural hearing loss: an immune-mediated
      response?
AB  - The authors propose the existence of a new entity of autoimmune sensorineural
      hearing loss on the basis of diagnostic study and treatment experience with a
      series of 30 patients. Immunological mechanisms play an important role in the
      pathogenesis and natural course of various inner-ear diseases. Patients may
      present clinically with symptoms resembling Meniere's disease or even with sudden
      deafness. Currently, no widely used standard protocol for treatment of this
      autoimmune sensorineural hearing loss exists. Prompted by such observations, we
      implemented a protocol using a particular kind of heparin--sodium enoxaparin-
      with a low molecular weight. Patients were randomly assigned to two groups; to
      those in the first group, enoxaparin was administered subcutaneously at a dose of
      2,000 IU twice daily for 10 days; the patients in the second group were treated
      with placebo. At the beginning and at the end of the therapy period, the patients
      were evaluated by instrumental examinations. Specifically excluded were patients
      with abnormal known coagulation. On discharge, all patients treated with
      enoxaparin presented both a subjective and objective decrease in symptoms. No
      patient experienced side effects from this treatment. The results indicate that
      administration of sodium enoxaparin abates sensorineural hearing loss in patients
      with autoimmune diseases. The clinical response to therapy can confirm diagnosis.

PMID- 16419688
TI  - Evoked response to taste stimulations.
AB  - For the recording of gustatory evoked responses, the tip of a stimulator is
      pressed vertically on one side of the tongue until the trigger pulses are
      generated by a switch attached to the bottom of the stimulator. According to our
      results, no detectable response was observed in the absence of taste. The
      positive waves were distinguishable by using the technique of superimposition
      before averaging, and the positive wave was made clearer by averaging.

PMID- 16419689
TI  - Vestibular evoked myogenic potentials in multiple sclerosis: a comparison between
      onset and definite cases.
AB  - Patients affected with multiple sclerosis (MS) frequently suffer from vestibular
      disorders due to vestibulospinal involvement. The vestibulospinal reflexes in
      these subjects can be well investigated through vestibular evoked myogenic
      potentials (VEMPs). Evoked by the acoustic stimulation of the saccular macula and
      mediated by the vestibulocollic reflex pathway, they are recorded using surface
      electromyographic electrodes from the ipsilateral sternocleidomastoid muscle
      tonically contracted. Abnormal findings (e.g., absence of response, prolonged
      latencies) disclose a lesion anywhere in the pathway. We examined VEMPs in 19
      patients with definite MS (5 men, 14 women; age range, 31-59 years; mean age, 45
      years) and compared them to VEMPs in 10 subjects with onset MS (2 men, 8 women;
      age range, 24-35 years; mean age, 29 years). VEMPs in definite MS subjects were
      abnormal in 14, absent (on the left side only) in 1, and normal in the remaining
      4. In patients with onset MS, VEMPs were abnormal in 6. These results suggest
      that latencies of vestibulospinal reflexes can be remarkably delayed in MS at
      different stages of disease, whereas vestibulospinal involvement is more frequent
      in definite cases. To date, no study has yet investigated different VEMPs
      involvement at different stages of MS.

PMID- 16419690
TI  - Saccadic and smooth-pursuit eye movement in neurootological diagnostic
      procedures.
AB  - The origin of the generation of saccadic and smooth-pursuit eye movements has not
      been proved. The goal of the study reported here was to search for the connection
      of visuooculomotor reactions--saccades and eye-tracking test--with cerebellar
      damage. Using electronystagmography, we tested 11 patients treated with
      aminoglycosides because of pneumonia. After a mean of 21 days of pharmacological
      therapy, a neurological examination revealed cerebellar disability in all cases.
      On the basis of our previous studies, we suspected cortical Purkinje cell damage.
      In all tested patients, saccadic movements were disturbed: We observed overshoot,
      undershoot, and prolonged latencies. In seven patients, eye-tracking test results
      were not correct: We noted the degradation of the sinusoidal pattern most often.
      The results pointed to a connection between the generation of these two tested
      visuooculomotor reactions with cerebellar diseases possibly located in the
      cortex.

PMID- 16419691
TI  - Electronystagmography outcome and neuropsychological findings in tinnitus
      patients.
AB  - Because psychological aspects often are underscored in the generation of
      tinnitus, we assessed the neuropsychological status in our group of patients. We
      found an increased number of abnormal electronystagmography (ENG) recordings in
      tinnitus patients. The aim of this study was to compare the ENG outcome with the
      patients' neuropsychological status. We carried out the study on 69 subjects
      complaining of tinnitus and on 43 healthy persons. We performed clinical
      neurootological examinations and ENG tests on all patients. Neuropsychological
      evaluation was conducted by means of the Beck Depression Inventory (BDI), the
      Hospital Anxiety and Depression (HAD) test, the Mini Mental Status (MMS) test,
      and the Trail-Making Test (TMT). In 46 patients (66.6%), we found abnormal ENG
      outcomes (central, 42%; peripheral, 13.0%; mixed, 11.6%). Neuropsychological
      tests revealed abnormal scores: for the BDI, 43.5% of patients; for the HAD-A,
      72.5%; for the HAD-D, 47.8%; for the MMS, 27.5%; and for the TMT, 55.1%. We did
      not find correlation between the ENG outcomes and neuropsychological test scores.
      We did not find correlation between the overall ENG outcomes and
      neuropsychological test scores, with one exception; we found the occurrence of
      abnormal neuropsychological test scores and the ENG outcome indicating central
      vestibular dysfunction. Our study showed that despite a high frequency of
      vestibular system dysfunction signs and a high incidence of abnormal
      neuropsychological test scores in tinnitus patients, only one correlation existed
      between these two results.

PMID- 16419692
TI  - Pulsed magnetic-field therapy: a new concept to treat tinnitus?
AB  - Both clinical and neurophysiological data suggest that chronic tinnitus is
      characterized by focal brain activation. In the study reported here, pulsed
      magnetic-field therapy induced a highly significant increase of average total
      power for the delta, theta, and alpha frequency bands, predominantly within the
      frontal regions of the brain. We conclude that pulsed magnetic-field therapy
      induces changes of the electroencephalography pattern that correlated with a
      decrease in tinnitus symptoms.

PMID- 16419693
TI  - Cochleovestibular dysfunction caused by cerebrovascular diseases.
AB  - When a vascular disorder of the cochleovestibular system is considered, the
      diagnosis is based on exclusion of other diseases. As arteries of the
      cochleovestibular system cannot be directly visualized, physicians must deduce
      vascular cochleovestibular disease from the vascular risk factors and vascular
      lesions of other territories. With my colleagues at Semmelweis University, I
      analyzed neurootological and audiological examination results in 65 patients with
      vascular vertigo. Cochleovestibular system disorders can be considered to be of
      vascular origin if the examinations exclude other diseases, if the patients have
      vascular risk factors, and if other territories of the brain accessible for
      imaging methods show vascular disorders.

PMID- 16419694
TI  - Meniere's disease and various types of vertigo in children.
AB  - Vertigo in children is less frequent than in adults, and examiners of patients
      showing these symptoms must rely on parents' or relatives' observations and
      details. Besides the equilibrium disorders caused by hereditary malabsorption
      syndromes or lesions in the peripheral and central vestibular structures, we know
      of typical diseases that are associated with vertigo and hearing problems and
      develop during childhood. One of them is Meniere's disease. Careful examinations
      are necessary to differentiate these illnesses from other vestibular disturbances
      accompanied by vertigo. Neurootological examinations in children, especially in
      small children, are more difficult than in adults. The reasons are the time
      consuming examination necessary in the case of children and the problems
      connected with a plethora of troublesome individual tests. Our study gives an
      overview of Meniere's disease and related vestibular disturbances occurring
      during childhood.

PMID- 16419695
TI  - Comparing neurootological complaints in patients at the end of their professional
      lives (51-60 years) with those during the first phase of retirement (61-70
      years).
AB  - Geriatrics defines the branch of medicine that treats all problems peculiar to
      old age and the aging, including the clinical problems of senescence and
      senility. In the full chain of years of the human life, a special period is
      humans' last decade of professional life (i.e., 51-60 years) and their first
      decade of retirement (i.e., 61-70 years). For this study aimed at comparing
      neurootological complaints of persons in this period of their lives, we examined
      large samples of European neurootological patients: Group A consisted of 1,965
      persons aged 51-60 years, and group B consisted of 1,032 persons aged 61-70
      years. Of the 11 vertigo and nausea symptoms evaluated, group A demonstrated 2.68
      signs and group B 2.49 signs per individual. Acoustic subjective symptoms of
      tinnitus were exhibited in 55.42% of group A patients, and hearing loss was
      present in 63.92% of these patients. In group B, 52.62% of patients exhibited
      tinnitus, and 68.31% of patients had hearing loss. Our experimental
      neurootometric investigations exhibited the following rates of abnormal test
      findings in group A: butterfly calorigrams, 71.86%; stepping craniocorpography,
      72.01%; and pure-tone audiometry of bone conduction, 37.66% in the right and
      47.07% in the left ear. Among group B patients, abnormal test findings were noted
      as follows: butterfly calorigrams, 69.86%; stepping craniocorpography, 74.03%;
      and pure-tone audiometry of bone conduction, 44.57% in the right and 55.43% in
      the left ear.

PMID- 16419696
TI  - Panic disorder in otoneurological experience.
AB  - The evaluation of cochleovestibular dysfunction in psychiatric patients often
      causes a difficult problem in neurootological experience. The authors discuss
      here the neurobiological basis of panic disorders and cochleovestibular
      dysfunction. In this multicenter study, we examined 63 patients with vertigo and
      panic disease. Twenty patients with primary panic disease and consecutive vertigo
      composed group 1, whereas group 2 comprised 43 vertiginous patients with
      secondary panic disease. The most interesting question is whether the patients
      have an organic vestibular lesion, which would explain why vertigo alone is the
      problematic symptom in these panic patients, whereas in other patients, panic
      disease can cause other severe symptoms that resemble heart attack, dyspnea, or
      abdominal crisis. Vertigo has a bidirectional connection with psychiatric
      disorders. The panic disorder can be superimposed on chronic vertigo, and
      psychiatric patients with a cochleovestibular lesion have diminished chances for
      complete recovery. The examination of psychiatric patients with vertigo is very
      time consuming and requires much more empathy than does examination of
      vertiginous patients with a normal mental state. Anxiety provokes somatic and
      behavioral symptoms in most such patients. The treatment of vertigo in panic
      patients and of the panic disorder in vertiginous patients requires cooperation
      between neurootologist and psychiatrist.

PMID- 16419697
TI  - Vestibular rehabilitation for migraine-associated dizziness.
AB  - The purpose of this study was to investigate the effects of a vestibular
      rehabilitation program on patients with the diagnosis of migraine-associated
      dizziness. Subjects were placed in four groups as follows: idiopathic migraine
      associated dizziness; idiopathic migraine-associated dizziness and associated
      benign positional vertigo; posttraumatic migraine-associated dizziness; and
      posttraumatic migraine-associated dizziness and benign positional vertigo.
      Vestibular rehabilitation therapy was administered to all patients. Criterion
      measurements included the dizziness handicap inventory, activities-specific
      balance confidence scale, computerized dynamic posturography performance, and
      dynamic gait index. After vestibular physical therapy, all subjects showed
      significant improvement in the dizziness handicap, activities-specific balance
      confidence, dynamic gait, and computerized dynamic posturography measures.
      Patients with migraine-associated dizziness can benefit from physical therapy
      intervention. The results of this study are important in considering the approach
      to vertiginous migraine patients with and without head injury.

PMID- 16419698
TI  - Auditory electrical tinnitus suppression in patients with and without implants.
AB  - The aim of this study was to evaluate the effectiveness of electrical tinnitus
      suppression in two groups of chronic severe tinnitus sufferers. Through standard
      tinnitus questionnaires, we compared the effectiveness of extratympanic and
      intratympanic auditory electrical stimulation (AES) by cochlear implants (CI) for
      the suppression or abolition of the perception of tinnitus and the decrease of
      its associated complaints. We made otolaryngological and comprehensive
      audiological assessment and also tinnitus measurement in each group of patients
      before and after AES and 50 days later. We investigated the dimensions of
      psychological complaints due to chronic and disabling tinnitus by means of the
      tinnitus questionnaire (TQ). The control examination during at least seven
      sessions (50 days) after AES in the group of patients without implants showed
      improvement in 20 of 32 patients (62.5%); 12 (37.5%) did not notice any change.
      In the comparative group of patients with implants, improvement occurred in 16 of
      20 patients (75%); during the switch-on of the speech processor, these patients
      reported significant attenuation or complete suppression of their tinnitus.
      Complete suppression of the tinnitus after CI was observed for 11 patients (55%),
      and 5 patients (25%) demonstrated significant attenuation of tinnitus.
      Nonsuppression of tinnitus was observed for only 4 patients (25%). None of our
      patients was affected by an increment in the tinnitus owing to CI. The
      differences of means of scores in the standard TQ were significant in both groups
      of patients. A comparison of TQ score differences between patients with and
      without implants showed no significance. We concluded that AES is a useful and
      effective therapeutic intervention in patients with tinnitus. Extratympanic AES
      reduces the effects of the tinnitus but presents limitations, mainly owing to the
      short duration of the electrical residual inhibition of the tinnitus. CI is shown
      to be more efficient for the treatment of tinnitus, mainly because the electrical
      stimulation affects a wider area of the cochlea and is presented for longer
      sessions. Therefore, patients affected by incapacitating tinnitus should be
      considered for continuous use of electrical stimulation.

PMID- 16419699
TI  - Medicolegal decision making in noise-induced hearing loss-related tinnitus.
AB  - In some patients with occupational noise-induced hearing loss, a significant
      aspect of the handicap concerns the concomitant tinnitus; thus, this disorder
      must be considered in evaluating a disability percentage in the insurance
      context. The main difficulty comes from the lack of objective measures for
      tinnitus. To reach a maximum of medicolegal objectivity, a system was developed
      within the Belgian Institute of Occupational Disorders (Brussels) in the form of
      a four-level decision structure, after exhaustive but noninvasive assessment of
      patients. An aggregate of multiple-choice responses (affirmative, neutral,
      negative) to elementary questions leads to a decision of the next level, which in
      turn determines--together with the other decisions at the same level--the
      conclusion at a still higher level. A positive outcome on all four level-3
      questions is required for recognition of noise-induced hearing loss-related
      tinnitus as an occupational disorder and for financial compensation (final
      decision, level 4). We assessed 10 exemplary files on which this system was
      applied by four experts rating independently. A variant of Cohen's Kappa for
      multiple raters demonstrated high interrater consistency at the first level. In
      all cases, the decisions at levels 3 and 4 were identical. In this way, the final
      medicolegal decision relies on standardized criteria and becomes perfectly
      transparent.

PMID- 16419700
TI  - [Effect of warming needle moxibustion on pain threshold in the patient of
      sciatica].
AB  - OBJECTIVE: To observe effect of warming needle moxibustion on pain threshold in
      the patient of sciatica. METHODS: Ninety cases were randomly divided into 3
      groups, 30 cases in each group. The warming needle moxibustion group were treated
      with warming needle moxibustion at Shenshu (BL 23), Dachangshu (BL 25), Huantiao
      (GB 30), etc; the western medicine group with oral administration of Nimeisulide;
      and the acupoint-injection group with injection of 654-2 into the same acupoints
      as those in the warming needle moxibustion group. RESULTS: The cured rates were
      56.67%, 26.67% and 20.00% in the 3 groups, and the total effective rate were
      90.00%, 73.33% and 63.33%, respectively, the therapeutic effect of the warming
      needle moxibustion group being better than those of other two groups (both P <
      0.01). The amplitude of pain threshold increase in the warming needle moxibustion
      group was higher than those of other two groups (both P < 0.01). CONCLUSION:
      Warming needle moxibustion can increase pain threshold, improve symptoms and
      raise quality of life for the patient of sciatica.

PMID- 16419701
TI  - [Effects of acupuncture on leptin level and relative factors in the simple
      obesity Uigur patient].
AB  - OBJECTIVE: To observe effects of acupuncture on BMI, WHR and serum levels of
      leptin and neuropeptide Y in simple obesity Uigur patients to research the
      mechanism of acupuncture in slimming. METHODS: Thirty simple obesity Uigur
      patients were treated with body acupuncture combined with electroacupuncture. Two
      courses later, their therapeutic effects were observed. And the above indexes
      were determined before and after treatment. RESULTS: The clinical total effective
      rate was 80.00%, and BMI, WHR, and the serum leptin level decreased (P < 0. 001).
      CONCLUSION: Uigur patients of simple obesity possibly exist resistance of leptin
      and acupuncture can decrease the peripheral leptin content.

PMID- 16419702
TI  - [Effect of acupuncture on plasma peptide YY in the patient of simple obesity].
AB  - OBJECTIVE: To observe changes of plasma peptide YY (PYY) in acupuncture for
      slimming. METHODS: Thirty-four cases of simple obesity were treated with
      acupuncture for 3 courses. Body mass index (BMI), and fat percent (F%), and
      insulin, PYY, blood fat, and blood sugar levels before and after treatment were
      determined, with 20 normal persons used as controls. RESULTS: The clinical total
      effective rate was 88.23%. Acupuncture could increase the decreased insulin
      sensitive index and PYY level (both P < 0.01), with no correlativity between them
      (P > 0.05). CONCLUSION: Regulation of PYY is possibly one of the mechanisms of
      acupuncture in slimming, but the relation of PPY with insulin resistance remains
      to be studied.

PMID- 16419703
TI  - [Controlled observation on acupuncture at Fengchi (GB 20) and Tianzhu (BL 10) for
      treatment of vertebrobasilar insufficiency].
AB  - OBJECTIVE: To evaluate clinical therapeutic effect of acupuncture at Fengchi (GB
      20) and Tianzhu (BL 10) on vertebrobasilar insufficiency (VBI). METHODS: One
      hundred and sixteen cases of VBI were randomly divided into 2 groups, 58 cases in
      each group. The treatment group were treated with acupuncture at Fengchi (GB 20)
      and Tianzhu (BL 10), and the control group with oral administration of
      Nimodipine. Clinical symptoms, and the average blood flow rates of left vertebral
      artery (LVA), right vertebral artery (RVA) and basilar artery (BA) detected by
      transcranial Doppler's method (TCD) before and after treatment were investigated.
      RESULTS: The total effective rate was 89.66% in the treatment group and 86.21% in
      the control group. Acupuncture had significantly therapeutic effect in
      improvement of clinical symptoms and the average blood flow rate of BA, better
      than Nimodipine. CONCLUSION: Acupuncture at Fengch; (GB 20) and Tianzhu (BL 10)
      has obvious therapeutic effect on vertebrobasilar insufficiency.

PMID- 16419704
TI  - [Effect of embedding thread at Shenshu (BL 23) on clinical pain of postmenopausal
      osteoporosis].
AB  - OBJECTIVE: To explore the effect of embedding thread at Shenshu (BL 23) on
      clinical pain of postmenopausal osteoporosis. METHODS: Fifty-six cases were
      randomly divided into an embedding thread group, an embedding thread plus Leli
      group and a Leli group. The pain of the patient before treatment, 3 months and 6
      months after treatment were assessed. RESULTS: There was significant difference
      before and after treatment in the score of pain in both the embedding thread
      group and the embedding thread plus Leli group (P < 0.001), with no significant
      difference between the two groups (P > 0.05); there was no significant difference
      before and after treatment in the score of pain in the Leli group (P > 0.05), but
      with significant differences as compared with other two groups (both P < 0.001).
      CONCLUSION: Embedding thread at Shenshu (BL 23) has very obvious therapeutic
      effect on clinical pain of postmenopausal osteoporosis, and oral administration
      of Leli capsule has no significantly therapeutic effect on clinical pain of
      postmenopausal osteoporosis.

PMID- 16419705
TI  - [Effect of acupuncture at Sishencong (EX-HN 1) on sleeping in the patient of
      insomnia].
AB  - OBJECTIVE: To assess therapeutic effect of acupuncture at Sishencong (EX-HN 1) on
      insomnia. METHODS: Sixty-five cases of insomnia were treated with acupuncture at
      Sishencong (EX-HN 1) and their quality and compositions of sleeping before and
      after treatment were evaluated with a multichannel sleep detector. RESULTS: After
      treatment, the quality of sleeping increased significantly (P < 0.05), and the
      sleeping rate increased from (61.95 +/- 22.90)% before treatment to (79.27 +/-
      11.05)% after treatment (P < 0.05). CONCLUSION: Acupuncture at Sishencong (EX-HN
      1) has obvious therapeutic effect on insomnia.

PMID- 16419706
TI  - [Observation on therapeutic effect of plum-blossom needle therapy on peripheral
      facial neuritis at acute stage].
AB  - OBJECTIVE: To compare difference between plum-blossom needle therapy and
      hormonotherapy in the The treatment group of 32 cases with periphtherapeutic
      effect on peripheral facial neuritis at acute stage. METHODS: eral facial
      neuritis at acute stage were treated with plum-blossom needle therapy and the
      control group of 32 cases with oral administration or intravenous drip of
      dexamethasone. Their therapeutic effects were compared. RESULTS: The total
      effective rate was 100.0% in the treatment group and 93.4% in the control group,
      with a significant difference between the two groups (P < 0.05). CONCLUSION: The
      therapeutic effect of plum-blossom needle therapy on peripheral facial neuritis
      at acute stage is better than that of the hormonotherapy.

PMID- 16419707
TI  - [Clinical observation on moving cupping therapy combined with moxibustion for
      treatment of senile habitual constipation].
AB  - OBJECTIVE: To explore an effective method for treatment of senile habitual
      constipation. METHODS: Sixty-four cases were randomly divided into a treatment
      group treated with moving cupping at Hechelu plus Shenque (CV 8) Bazhenxue
      moxibustion, and a control group with oral administration of Tab
      phenolphthaleinum, 32 cases in each group. Improvement of constipation in the
      patients were observed and compared. RESULTS: The short-term (14 days) clinical
      cured-markedly effective rate was 84.4% in the treatment group, which was
      significantly better than 59.4% of the control group (P < 0.05), and there was a
      significant difference between the two groups in the long-term (2 months)
      therapeutic effect (P < 0. 01). CONCLUSION: Moving cupping at the Hechelu
      combined with Shenque (CV 8) Bazhenxue moxibustion is an effective method for
      senile habitual constipation.

PMID- 16419708
TI  - [Clinical study on method of "tonifying the lung to check the liver" for
      treatment of chronic cholecystitis].
AB  - OBJECTIVE: To evaluate the significance of method of "tonifying the lung to check
      the liver" for treatment of chronic cholecystitis. METHODS: Forty cases were
      randomly divided into a treatment group and a control group. The treatment group
      were treated with acupuncture and moxibustion by the method of "tonifying the
      lung to check the liver", and the control group with routine moxibustion.
      RESULTS: After treatment of one day, pain improved significantly in the two
      groups (P < 0.001), with no significant difference between the two groups; and 15
      days after treatment, the treatment group was superior to the control group in
      the improvement of pain. CONCLUSION: TCM syndrome differentiation has an
      important significance in clinical acupuncture and moxibustion, and the
      therapeutic principle "tonifying the lung to check the liver" in classical TCM
      theories is of scientific basis.

PMID- 16419709
TI  - [Observation on clinical therapeutic effect of acupoint-injection therapy
      combined with prednisone on nephrotic syndrome and effect on immunologic
      function].
AB  - OBJECTIVE: To search for the best method for increasing clinical therapeutic
      effect on nephrotic syndrome. METHODS: Forty-one cases were randomly divided into
      2 groups. The treatment group (n=22) were treated with acupoint-injection of
      Chinese medicine combined with prednisone, and the control group (n=19) with
      prednisone. Their therapeutic results were observed and compared. RESULTS: The
      complete remission rate of 45.5% and the total effective rate of 86.4% in the
      treatment group were significantly higher than 31.6% and 63.2% in the control
      group, with a significant difference between the two groups in the total
      effective rate (P < 0.05); in the treatment group, blood lipids decreased, plasma
      proteins raised and immunologic function improved. CONCLUSION: Acupoint-injection
      of Chinese medicine combined with prednisone can significantly increase
      therapeutic effect on nephrotic syndrome and strengthen immunologic function.

PMID- 16419710
TI  - [Observation on relation of acupuncture at Guangming (GB 37) and Taichong (LR 3)
      with central nervous reaction].
AB  - OBJECTIVE: To observe relative effects of acupuncture at Guangming (GB 37) and
      Taichong (LR 3) in central different regions. METHODS: Nineteen healthy
      volunteers were randomly divided into 3 groups: group I (n=7) received visual
      stimulation and acupuncture at one side; group II (n=6) received visual
      stimulation and acupuncture at both sides; and group III (n=6) received
      acupuncture at both sides. Functional magnetic resonance imaging (fMRI) was used
      to investigate reactions of the different visual cortexes and relative cerebral
      regions in acupuncture at Guangming (GB 37) and Taichong (LR 3). RESULTS: There
      was no significant change in blood oxygen saturation levels in the visual cortex
      at visual stimulation and insertion of the needle, but there were changes in
      blood oxygen saturation level in relative cerebral regions when continuous
      stimulation was given to one-side or both sides. CONCLUSION: Acupuncture at one
      side or both sides can improve blood oxygen saturation level in relative cerebral
      regions, which is not related with manipulation method and visual stimulation.

PMID- 16419711
TI  - [Study on needling depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5)
      and Mingmen (GV 4) with CT].
AB  - OBJECTIVE: To provide reference for the safe needling depth of Dazhui (GV 14),
      Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4) in clinical acupuncture
      and moxibustion treatment. METHODS: Thirty-two adult volunteers were divided into
      3 groups, thin person group, moderate person group and fat person group according
      to Luo's indexes, and computer-aided tomography was used to measure the needling
      depth of Dazhui (GV 14), Jianzhongshu (SI 15), Xuanshu (GV 5) and Mingmen (GV 4).
      RESULTS: The safe depths of perpendicular needling were different for persons of
      different somatotypes, for example the needling depth for Dazhui (GV 14) was
      (32.86 +/- 3.96) mm for the thin person group, (37.76 +/- 4.91) mm for the
      moderate person group, and (47.93 +/- 5.30) mm for the fat person group.

PMID- 16419712
TI  - [Preparation, manipulation and clinical application of prof. HUANG Di-jun's
      moxibustion with seed-sized moxa cone].
AB  - Manipulation method and clinical application of Prof. HUANG Di-jun's moxibustion
      with seed-sized moxa cone are introduced from preparation of argyi wool,
      manipulation, matters needing attention, indications, and clinical
      characteristics of moxibustion with seed-sized moxa cone, etc. So as to
      popularize moxibustion with seed-sized moxa cone.

PMID- 16419713
TI  - [My opinion on academician SHI Xue-min's thought about spirit in acupuncture].
AB  - Academician SHI Xue-min emphasizes application of spirit in acupuncture
      technique, and considers that keeping spirit is the first task for acupuncture,
      reaction of spirit is a guarantee for producing the effect, acupuncture must
      require the reaction of spirit in needling, and raises location, governing,
      disease, and treatment of the spirit. Thus, the intension of the spirit is
      analyzed from physiology, pathology and treatment of the spirit, forming academic
      system of the spirit.

PMID- 16419714
TI  - [Acupuncture and moxibustion for treatment of pain in Austria].
AB  - The author treated 1252 Europeans with various kinds of pain, including 7 kinds
      of pain such as lumbocrural pain, headache, pain in neck and nape and others, in
      Klagenfurt Hospital of Austria with acupuncture using uniform reinforcing
      reducing manipulation, and with a fixed prescription, twice each week, 10
      sessions constituting one course. The pain indexes before and after treatment
      were evaluated by local medical experts. It was indicated that the pain index was
      decreased by 70.08%.

PMID- 16419715
TI  - [Effect of electroacupuncture on hemodynamics at peri-intratracheal intubation
      period under general anesthesia].
AB  - OBJECTIVE: To observe effect of electroacupuncture on hemodynamics at peri
      intratracheal intubation period under general anesthesia. METHODS: Sixty cases at
      peri-intratracheal intubation period under general anesthesia were randomly
      divided into electroacupuncture group [Before anesthesia induction,
      electroacupuncture stimulation was given at Neiguan (PC 6), Hegu (LI 4), Quchi
      (LI 11), Shenmen (HT 7)], and control group, 30 cases in each group. All the
      patients in the two groups received intratracheal intubation with light-guide
      laryngoscopy under general anesthesia with midazolam, fentanyl, isopropyl,
      succinylcholine, etc.; changes of various indexes of hemodynamics were detected
      at anesthesia induction and different time points of the intubation. RESULTS: At
      the anesthesia induction, various indexes of hemodynamics in the
      electroacupuncture group were relatively stable, and decreased significantly in
      the control group (P < 0.01); during intratracheal intubation, the various
      indexes in the electroacupuncture group (P < 0.05) and in the control group (P <
      0.01) increased significantly as compared with those before anesthesia induction;
      5 min after intubation, the various indexes in both the two groups restored
      normal. CONCLUSION: Electroacupuncture at Neiguan (PC 6) and other points can
      stabilize changes of hemodynamics at the intratracheal intubation and increase
      safety of operation under anesthesia.

PMID- 16419716
TI  - [Role of acupuncture anesthesia in operation of rectal cancer].
AB  - OBJECTIVE: To observe analgesic effect of acupuncture anesthesia. METHODS: Sixty
      nine cases undergoing rectal cancer surgery were randomly divided into 3 groups,
      group I, II and III, 23 cases in each group. Both Zusanli (ST 36) and Sanyinjiao
      (SP 6) were selected for acupuncture anesthesia. Group I received general
      anesthesia after acupuncture induction, group II received acupuncture after
      general anesthesia, and group II received only general anesthesia. Minimum
      alveolar concentration (MAC) before and after operation was recorded. RESULTS:
      MAC was (1.35 +/- 0.19) vol% in the group I, (1.49 +/- 0.22) vol% in the group II
      and (1.64 +/- 0.27) vol% in the group III. Acupuncture before and after general
      anesthesia could decrease respectively by about 0.29% and 0.15% of MAC in rectal
      cancer surgery undergoing general anesthesia, with a very significant difference
      (P < 0.01) or a significant difference (P < 0.05) among the 3 groups. CONCLUSION:
      Acupuncture anesthesia has a certain adjuvant action for anesthesia and
      analgesia, and acupuncture before general anesthesia has a better action.

PMID- 16419717
TI  - [Effects of electroacupuncture on neurological deficit and pathomorphologic
      lesion in the rat of focal cerebral ischemia].
AB  - OBJECTIVE: To probe into regularity of effects of electroacupuncture on focal
      cerebral infarction. METHODS: Focal cerebral ischemia model was established by
      middle cerebral artery heat-occlusion (MACO) method. Electroacupuncture was given
      at Dazhui (GV 14) and Baihui (GV 20). NSS was used for evaluation of neurological
      impairment, TTC staining method for detection of the infarct volume, and HE
      staining method for investigation of the pathomorphologic lesion of the brain.
      RESULTS: MCAO could induce neurologic impairment, cerebral infarction and
      cerebral pathological lesion in the rat, all of these changes could be cured
      spontaneously in varying degrees with prolongation of ischemic time, but
      electroacupuncture could relieve the lesions to a certain extents. CONCLUSION:
      Electroacupuncture can improve neurologic deficit impairment, reduce the volume
      of cerebral infarction and ischemic pathological lesion, early interfere of
      acupuncture and moxibustion is of very important clinical significance for
      treatment of ischemic apoplexy.

PMID- 16419718
TI  - [Simple analysis on collateral therapy in Huangdi's Internal Classic].
AB  - Collateral therapy includes treatment of diseases of collaterals, and treatment
      of human other diseases with collaterals as treating subjects. In collateral
      therapy of Huangdi's Internal Classic, collaterals were used as treating
      subjects, and the treatment was directly given at the collaterals of lesion; for
      treatment methods, acupuncture and moxibustion were adopted as main method,
      including pricking blood therapy, moxibustion of collaterals, acupuncture; the
      diseases and syndromes of treatment included diseases and syndromes of channels
      and collaterals, and human other diseases and syndromes; the principles of
      reinforcing and reducing, and the principles of treatment varying from time to
      time were stressed, and it indicated contraindications for treatment.

PMID- 16419719
TI  - [Evaluation of the literatures of clinical studies on acupuncture and moxibustion
      for treatment of sensorineural hearing loss].
AB  - OBJECTIVE: To understand the survey of studies on acupuncture and moxibustion for
      treatment of sensorineural hearing loss at home. METHODS: By searching China
      journal web, 60 correlative papers from Jan. 1994 to Aug. 2004 were found and
      analyzed. RESULTS: Descriptive studies accounted for 71.7% and trial studies
      accounted for 28.3%. The diseases studied were mainly sudden deafness and the
      treatment methods were principally auricular acupuncture and body acupuncture.
      Most papers did not have definite diagnosis standard, and most criteria of
      therapeutic effects were self-stipulated, with no detail processing methods for
      the results, and only one paper reported adverse reaction. CONCLUSION: The
      therapeutic effects of acupuncture and moxibustion on sensorineural hearing loss
      need to be confirmed with studies of higher quality.

PMID- 16419720
TI  - The science, studies and sociology of the abortion breast cancer link.
AB  - This article explains the breast physiology and epidemiologic criteria supporting
      the abortion breast cancer link and the sociologic factors that cause this risk
      to remain largely unknown to both medical professionals and the public. Abortion
      increases breast cancer risk through multiple mechanisms. Pregnancy exposes women
      to high levels of estrogen acting as a mitogen and genotoxin, and induced
      abortion then leaves their breasts with more places for cancers to start. They
      have a higher risk of subsequent premature deliveries that further increase their
      risks of breast cancer. Rampant breast cancer seen in ever younger women will not
      allow this issue to be suppressed.

PMID- 16419721
TI  - The abortion-breast cancer connection.
AB  - This article examines the abortion breast cancer link in some historical
      scientific detail, offering a perspective on an issue that is at the center of a
      long-running public policy debate that plays out in legislatures, courtrooms, and
      newspaper editorials, as well as in scientific and medical journals. Even as
      politically correct studies have been promulgated to neutralize the data proving
      the abortion breast cancer link, even stronger data have emerged in recent years
      that firmly link abortion to premature births in subsequent pregnancies, which in
      turn raise the risk of breast cancer in mothers and cerebral palsy in prematurely
      born children.

PMID- 16419722
TI  - Preston v. Meriter Hospital in the Supreme Court of Wisconsin.
AB  - When a baby is born in a hospital birthing center, the newborn has come to the
      "emergency department" for purposes of the Emergency Medical Treatment and Active
      Labor Act (EMTALA). Thus, the hospital must provide "an appropriate medical
      screening examination" to any infant born at the hospital birthing center in
      order to determine whether the infant has an emergency medical condition.

PMID- 16419723
TI  - Brief of Amicus Curiae Eagle Forum Education & Legal Defense Fund in support of
      petitioner.

PMID- 16419724
TI  - Cancer facts: abortion, miscarriage, and breast cancer risk.

PMID- 16419725
TI  - Summary report: early reproductive events and breast cancer workshop.

PMID- 16419726
TI  - Abortion and breast cancer: the unproven link.

PMID- 16419727
TI  - Poisonings.

PMID- 16419728
TI  - This issue: Managing emergencies part 2.
AB  - Pediatric toxicologic exposures are common, and the primary care pediatric
      practitioner must be prepared to handle emergencies related to poisoning and
      overdose in children and adolescents. Fortunately, many poisonings in children
      are unintentional, preventable, and benign. For both simple and complex cases,
      help is available to medical professionals 24/7 from multiple sources, including
      an improved toxic exposure database, new research, the network of Certified
      Specialists in Poison Information at our nation's regional poison control
      centers, and backup medical and clinical toxicologists. The US system of AAPCC
      certified poison control centers has been appropriately labeled "a national
      safety net" serving the public and medical practitioners in the management of
      pediatric toxicologic exposures. Increased funding to this system will be
      critical to update its services for the future, including preparation to detect
      the increasing threat of new public health emergencies such as chemical and
      biological terrorist attacks.

PMID- 16419729
TI  - A 15-year-old girl with a 45-lb weight loss.

PMID- 16419730
TI  - A 13-year-old girl with a breast mass.

PMID- 16419731
TI  - Diagnosis and management of the poisoned child.
AB  - Pediatric toxic ingestions are treated commonly by pediatricians and emergency
      physicians. Significant injury after these ingestions is infrequent, but
      identifying the dangerous ingestion is sometimes a difficult task. By performing
      a detailed history, focused physical examination, and directed laboratory
      evaluation, an estimation of risk can be developed. This article introduced the
      term "toxic triage" to describe this process. The toxic triage estimation allows
      the clinician to make thoughtful decontamination and treatment decisions.
      Familiarity with the literature supporting or refuting each decontamination
      method allows educated decisions to be made. Supportive care is an integral part
      of treatment for all poisonings, from asymptomatic to life-threatening. Most
      antidotes are used rarely in clinical practice, but familiarity with common
      antidotes benefits those patients with specific hazardous ingestions. Prevention
      efforts have the potential to decrease the incidence of pediatric poisonings. The
      universal poison control center number provided should be distributed and posted
      in homes, clinics, and emergency departments.

PMID- 16419732
TI  - Managing adverse reactions to psychotropic medications.

PMID- 16419733
TI  - Adolescent substance abuse: a simplified approach to drug testing.
AB  - Treatment of adolescent substance abusers is difficult. Treatment programs at
      multiple levels, from inpatient facilities to outpatient support groups, usually
      are available. Some of the most encouraging results have come from programs that
      involve family therapy in addition to individual treatment. 22 Knowing what
      resources are available, as well as the referral processes based on a particular
      patient's healthcare plans, facilitates access and makes dealing with these
      issues in a busy outpatient setting much easier. Frequent follow-up with an
      adolescent after a treatment program has been initiated to monitor for compliance
      and relapse can ensure a better drug-free outcome. Knowing the extent of the
      adolescent drug abuse problem should encourage providers to incorporate some type
      of screening into their routine care of adolescents. None of these methods is
      100% sensitive, and incorporating each component into the process where
      appropriate likely is the best approach. Knowing risk and protective factors for
      drug use is helpful for both recognition of candidates for screening and
      counseling of parents regarding drug use prevention.

PMID- 16419734
TI  - One pill can kill: assessing the potential for fatal poisonings in children.
AB  - Antimalarials, camphor, clonidine, methyl salicylates, and sulfonylureas all may
      result in serious poisonings and are potentially fatal in small doses in
      toddlers. Early recognition and appropriate management, including antidotal and
      supportive care, may prevent poor outcomes in these patients.

PMID- 16419735
TI  - Case studies in pediatric toxicology.
AB  - Intentional and unintentional poisonings are encountered commonly in the
      pediatric population. Providers should be familiar both with the general approach
      to the poisoned child and with specific interventions required for certain toxic
      exposures.

PMID- 16419736
TI  - Understanding poison control and protecting its future.
AB  - Poison centers save money and lives. Individual patients and their doctors
      benefit from local poison center availability, as do healthcare facilities and
      insurance companies. All have a stake in a stable poison control system. It is
      likely that the greatest contribution of poison control centers to society has
      yet to be realized. Poison control centers already possess an efficient, realtime
      surveillance mechanism (TESS). With increased funding, this can be expanded and
      made more available outside the poison control community. TESS can be used to
      detect chemical releases or attacks and environmental and infectious disease
      outbreaks as they occur - long before individual healthcare providers could
      connect the dots. In conclusion, while the value of a nationwide poison control
      system to society is well recognized, its future is not as clear. Establishing a
      stable system to monitor and treat poisonings in the US will take political will
      at the local, state, and federal levels to ensure full funding for years to come.

PMID- 16419738
TI  - Both heat-shock and cold-shock influence trehalose metabolism in an
      entomopathogenic nematode.
AB  - Heat-shock response is highly conserved in animals and microorganisms, and it
      results in the synthesis of heat-shock proteins. In yeast, heat-shock response
      has also been reported to induce trehalose accumulation. We explored the
      relationship between heat- (35 C) or cold-shock (1 and 10 C) and trehalose
      metabolism in the entomopathogenic nematode, Heterorhabditis bacteriophora.
      Because both heat- and cold-shocks may precede desiccation stress in natural soil
      environments, we hypothesized that nematodes may accumulate a general desiccation
      protectant, trehalose, under both situations. Indeed, both heat- and cold-shocks
      influenced trehalose accumulation and activities of enzymes of trehalose
      metabolism in H. bacteriophora. Trehalose increased by 5- and 6-fold in heat- and
      cold-shocked infective juveniles, respectively, within 3 hr of exposure, compared
      with the nematodes maintained at 25 C (culture temperature). The activity of
      trehalose-6-phosphate synthase (T6PS), an enzyme involved in the synthesis of
      trehalose, also significantly increased in both heat- and cold-shocked nematodes
      during the first 3 hr of exposure. Generally, the trehalose levels and activities
      of T6PS declined to their original levels within 3 hr when nematodes were
      transferred back to 25 C. In both heat- and cold-shocked nematodes, trehalase
      activity decreased significantly within the first 3 hr and generally returned to
      the original levels within 3 hr when these nematodes were transferred back to 25
      C. The results demonstrate that the trehalose concentrations in H. bacteriophora
      are influenced by both heat- and cold-shocks and are regulated by the action of 2
      trehalose-metabolizing enzymes, T6PS and trehalase. The accumulated trehalose may
      enhance survival of nematodes under both cold and warm conditions, but it may
      also provide simultaneous protection against desiccation that may result from
      subsequent evaporation or freezing. This is the first report of the relationship
      between trehalose metabolism and heat-shock for the Nematoda.

PMID- 16419737
TI  - Characterization of excretory/secretory endopeptidase and metallo-aminopeptidases
      from Taenia crassiceps metacestodes.
AB  - Cysticercosis is caused by Taenia spp. metacestodes, which must survive in the
      host tissues to complete their life cycle. Their survival depends on their
      control of host immune responses. Because many parasites use proteases to
      modulate host responses, we examined culture media from Taenia crassiceps
      metacestodes for protease activity using peptide substrates. We identified
      prominent aminopeptidase activity at neutral pH, which was inhibited by chelating
      agents and partially inhibited by the aminopeptidase inhibitor, bestatin.
      Endopeptidase substrates were optimally cleaved at slightly acidic pH and
      endopeptidase activity was inhibited by cysteine protease inhibitors. Gel
      filtration FPLC and subsequent visualization by silver staining revealed a
      metallo-aminopeptidase of molecular weight 21 kDa and cysteine proteases of Mr 70
      and 64 kDA. Recombinant IL-2 was digested when incubated with parasite culture
      supernatants, but not with control media. IL-2 degradation was completely
      inhibited by 1,10 phenanthroline and partially inhibited by bestatin, suggesting
      that a metallo-aminopeptidase was responsible. Incubation of human IgG with
      culture supernatants resulted in complete degradation of IgG, which was blocked
      by cysteine protease inhibitors. These observations demonstrate that Taenia spp.
      metacestodes secrete a number of proteolytic enzymes, which may target molecules
      from the host immune system and assist in evasion of the host immune response.

PMID- 16419739
TI  - Distribution of Cryptosporidium parvum sporozoite apical organelles during
      attachment to and internalization by cultured biliary epithelial cells.
AB  - Although accumulating evidence supports an active role for host cells during
      Cryptosporidium parvum invasion of epithelia, our knowledge of the underlying
      parasite-specific processes triggering such events is limited. In an effort to
      better understand the invasion strategy of C. parvum, we characterized the
      presence and distribution of the apical organelles (micronemes, dense granules,
      and rhoptry) through the stages of attachment to, and internalization by, human
      biliary epithelia, using serial-section electron microscopy. Novel findings
      include an apparent organized rearrangement of micronemes upon host cell
      attachment. The apically segregated micronemes were apposed to a central
      microtubule-like filamentous structure, and the more distal micronemes localized
      to the periphery and apical region of the parasite during internalization,
      coinciding with the formation of the anterior vacuole. The morphological
      observations presented here extend our understanding of parasite-specific
      processes that occur during attachment to, and internalization by, host
      epithelial cells.

PMID- 16419740
TI  - Mode of transmission, host switching, and escape from the Red Queen by viviparous
      gyrodactylids (Monogenoidea).
AB  - Compared to other monogenoidean groups, viviparous gyrodactylids exhibit
      extraordinary species diversity and broad host range. It has been suggested that
      this evolutionary success is associated with a suite of morphological and life
      history traits that include, in part, continuous transmission (i.e., ability to
      infect new hosts throughout the gyrodactylid life cycle). Experiments were
      conducted to explore the putative adaptive advantage of continuous transmission
      within viviparous gyrodactylids during colonization of new host resources.
      Differences in infrapopulation growth, such as abundance, prevalence, and
      duration of the infection, of Gyrodactylus anisopharynx on 3 species of fish-
      Corydoras paleatus and Corydoras ehrhardti (both natural hosts) as well as
      Corydoras schwartzi (a host not known to harbor G. anisopharynx)--held under
      isolated and grouped conditions were determined. Results showed that
      infrapopulations of G. anisopharynx on C. paleatus and C. schwartzi had higher
      growth when the parasite had the opportunity for host transfer (grouped hosts).
      Infrapopulations of G. anisopharynx on isolated and grouped C. ehrhardti showed
      an opposite trend, although differences in mean duration and maximum abundance
      were not statistically different. Results obtained from experiments with C.
      paleatus and C. schwartzi support the hypothesis that continuous transmission in
      viviparous gyrodactylids enhances colonization success, probably by allowing
      initial avoidance of Red Queen dynamics. The absence of statistical differences
      between infrapopulations on isolated and grouped C. ehrhardti suggests that
      parasite dynamics may be influenced by factors other than continuous transmission
      in this host.

PMID- 16419741
TI  - Temporal variation in the infection dynamics and maturation cycle of
      Oligogonotylus manteri (Digenea) in the cichlid fish, 'Cichlasoma' urophthalmus,
      from Yucatan, Mexico.
AB  - We studied the infection dynamics and maturation cycle of Oligogonotylus manteri
      in wild and caged 'Cichlasoma' urophthalmus, and determined the potential role of
      different sources of infection in its transmission in a quarry (MITZA).
      Metacercariae, and nongravid and gravid stages of O. manteri were present
      throughout 1 annual cycle. Prevalence, mean intensity, and/or aggregation values
      peaked around April and June in both wild and caged fish. This period of time
      includes the start of the rainy season, in which the water temperature reaches
      its maximum annual values. Because temperature is a major factor triggering 'C.'
      urophthalmus activity (food intake, growth, and reproduction), and O. manteri
      metacercariae and adults are trophically transmitted, temperature may be playing
      an important role in the recruitment of worms to the fish. We also determined
      that cercariae infect caged fish through a mechanism other than trophic
      transmission whereby fish consume infected snails, which has been described as
      the most common mode of transmission to 'C.' urophthalmus.

PMID- 16419742
TI  - A faunal survey of streblid flies (Diptera: Streblidae) associated with bats in
      Paraguay.
AB  - An extensive survey of the ectoparasites infesting bats in Paraguay provides
      information regarding the taxonomy and host distribution of streblid bat flies at
      a geographic interface between subtropical and temperate habitats. Five families
      of bats representing 45 species, including Molossidae (5 genera and 15 species),
      Natalidae (1 genus and 1 species), Phyllostomidae (11 genera and 15 species),
      Noctilionidae (1 genus and 2 species), and Vespertilionidae (4 genera and 12
      species) were collected from 24 localities across Paraguay and sampled for
      ectoparasites. In total, 2,467 bat flies were collected, representing 11 genera
      and 31 nominal species of Streblidae, of which 6 genera and 24 species are new
      records for Paraguay. No streblids were collected from vespertilionid bats; 23
      species infested phyllostomids, 6 species noctilionids, 1 species a natalid, and
      1 species molossids. Streblid bat flies were highly specific to certain host
      groups and individual host species, and their geographic distributions closely
      followed those of their host bats. Of 31 streblid species surveyed, 27 were
      monoxenous (i.e., associated with a single host species), and 4 were stenoxenous
      (i.e., associated with a group of phylogenetically related hosts). The number of
      streblid species is greatly reduced in the Chaco region west of the Paraguay
      River, largely because of the lack of phyllostomid host bats.

PMID- 16419743
TI  - Neotropical Monogenoidea: Euryhaliotrema dontykoleos n. sp. (Dactylogyridae) from
      the gills of the freshwater sciaenid, Pachyurus junki (Perciformes).
AB  - Euryhaliotrema dontykoleos n. sp. (Monogenoidea, Polyonchoinea, Dactylogyridae)
      is described based on specimens collected from the gills of Pachyurus junki
      (Teleostei, Sciaenidae, Pachyurinae) in the Rio Tocantins and its tributaries,
      State of Tocantins, Brazil. The new species, the first species of Monogenoidea
      reported from a pachyurine, is easily differentiated from its congener by the
      presence of toothlike projections in the border of the vaginal opening and by
      having a trapezoidal anteromedial projection on the ventral bar. Phylogenetic
      analysis indicates that the new species is not a member of the clade that
      includes the Euryhaliotrema spp. from Plagioscion spp., a second lineage of
      freshwater sciaenids in South America. Euryhaliotrema dontykoleos shares an
      immediate ancestor with the clade formed by parasites infecting marine
      Paralonchurus spp., (Sciaenidae), and those of Plagioscion spp.

PMID- 16419744
TI  - The L3 to L4 molt of Brugia malayi: real time visualization by video microscopy.
AB  - Brugia malayi and other filarial parasites have been studied in great detail,
      especially in the context of human disease. In common with other nematodes, these
      organisms molt 4 times in their life cycles, but details of this process have not
      been described. We have recently developed an in vitro culture system that
      supports the L3 to L4 molt at high efficiency. This has permitted us to
      visualize, for the first time, details of this molt using real-time video
      microscopy. Molting is preceded by a phase of altered motility during which the
      larva exhibits contractile, coiling movements. The earliest evidence of ecdysis
      is a clearing at one end, more frequently caudal, caused by the larva retracting
      from that end. A cleavage develops in the cuticle near the head end, forming a
      rostral cap, which is continuous with the pharyngeal cuticle. Simultaneously, it
      retracts out of the cuticle using coiling and writhing movements. This process
      takes 5 to 10 min. Finally, it retracts out of the cap and extrudes the
      pharyngeal cuticle. Detachment of the pharyngeal cuticle is the final event in
      the process and continues up to an hour after the rest of the cuticle has been
      shed.

PMID- 16419745
TI  - Electron microscopic observation of the invasion process of Cryptosporidium
      parvum in severe combined immunodeficiency mice.
AB  - Cryptosporidium parvum mainly invades the intestinal epithelium and causes watery
      diarrhea in humans and calves. However, the invasion process has not yet been
      clarified. In the present study, the invasion process of C. parvum in severe
      combined immunodeficiency (SCID) mice was examined. Infected mice were
      necropsied; the ilea were double-fixed routinely and observed by scanning and
      transmission electron microscopy. In addition, the microvillus membrane was
      observed by ruthenium red staining. Scanning electron micrographs showed
      elongation of the microvilli at the periphery of the parasite. The microvilli
      were shown to be along the surface of the parasite in higher magnification.
      Transmission electron microscopy confirmed that the invading parasites were
      located among microvilli. Parasites existed in the parasitophorous vacuole formed
      by the microvillus membrane. The parasite pellicle attached to the host cell
      membrane at the bottom of the parasite, and then the pellicle and host cell
      membrane became unclear. Subsequently, the pellicle became complicated and formed
      a feeder organelle. In addition, invasion of the parasite was not observed in
      either a microvillus or the cytoplasm of the host cell. Therefore, C. parvum
      invades among microvilli, is covered with membranes derived from numerous
      microvilli, and develops within the host cell.

PMID- 16419746
TI  - A molecular phylogenetic study of the genus Ribeiroia (Digenea): trematodes known
      to cause limb malformations in amphibians.
AB  - Species of Ribeiroia (Trematoda: Psilostomidae) are known to cause severe limb
      malformations and elevated mortality in amphibians. However, little is known
      regarding the number of species in this genus or its relation to other taxa.
      Species of Ribeiroia have historically been differentiated by slight differences
      among their larval stages. To better understand the systematics and biogeography
      of this genus and their potential relevance to the distribution of malformed
      amphibians, specimens identified as Ribeiroia were collected across much of the
      known range, including samples from 5 states in the United States (8 sites) and 2
      islands in the Caribbean (Puerto Rico and Guadeloupe). A cercaria from East
      Africa identified as Cercaria lileta (Fain, 1953), with attributes suggestive of
      Ribeiroia (possibly R. congolensis), was also examined. The intertranscribed
      spacer region 2 (ITS-2) of the ribosomal gene complex was sequenced and found to
      consist of 429 nucleotides (nt) for R. ondatrae (United States) and 427 nt for R.
      marini (Caribbean), with only 6 base differences noted between the 2 species. The
      ITS-2 region of C. lileta (429 nt) aligned closely with those of the 2 other
      Ribeiroia species in a phylogenetic analysis that included related trematode
      genera. This evidence suggests that a third Ribeiroia species exists in tropical
      Africa. Variation in ITS-2 within R. ondatrae was nonexistent among the 8
      populations from North America. Our study further suggests that Ribeiroia spp.
      originally parasitized Biomphalaria sp., and that a host switch to a closely
      related snail, Helisoma sp., may have occurred in the lineage represented by R.
      ondatrae. However, relationships within the Echinostomatidae are not understood
      well enough to make any robust conclusions at this time.

PMID- 16419747
TI  - Differences in shell shape of naturally infected Lymnaea stagnalis (L.)
      individuals as the effect of the activity of digenetic trematode larvae.
AB  - The shells of Lymnaea stagnalis show great morphological variability. This
      phenomenon has been described as the result of an environmental influence. The
      main object of the present study was to compare some biometric data from shells
      of naturally infected and uninfected snails from 25 different lakes in the
      central part of Poland. The height of the shell, the height of the spiral, and
      the width of the shell were measured. Some inter- and intrapopulation differences
      among individuals were found. Greater variability of shell shape was observed
      among snails parasitized with digenean larvae than in nonparasitized ones. Snails
      infected with Echinoparyphium aconiatum, Echinostoma revolutum, Diplostomum
      pseudospathaceum, and Opisthioglyphe ranae differed in shell shape compared with
      uninfected individuals. Snails infected with Plagiorchis elegans did not differ
      from uninfected individuals. The same was true of snails in which the commensal
      oligochaete, Chaetogaster limnei, was found. The results of the present study
      support the assumption that the deformation of shells of the snails under study
      was in some way influenced by the presence of certain species of digenetic
      trematodes.

PMID- 16419748
TI  - NAD(P)H-oxidase presence in Toxoplasma gondii tachyzoite vacuole during
      interaction with IFN-gamma-activated human endothelial cells.
AB  - Toxoplasma gondii invades and proliferates in human umbilical vein endothelial
      cells (HUVEC) where it resides in a parasitophorous vacuole (PV) preventing
      lysosomal fusion. To study the intracellular outcome of PV containing tachyzoites
      of T. gondii during interaction with IFN-gamma-activated HUVEC, a quantitative
      analysis of the T. gondii infection and multiplication was assayed. The
      quantification of PVs' fusion with lysosomes, ultrastructural examination of
      phagosome-lysosome fusion, and the localization of NAD(P)H-oxidase activity were
      also investigated. HUVEC activated with IFN-gamma inhibited T. gondii infection
      and multiplication by 67.5% and 91.0%, respectively. After 4 hr of infection,
      10.2% of IFN-gamma-activated HUVEC exhibited phagosome-lysosome fusion assayed by
      fluorescence microscopy, which was also observed at the ultrastructural level.
      Furthermore, the enzyme NAD(P)H-oxidase present at the plasma membrane of
      activated HUVEC was internalized together with the parasite in 38.0% of the
      cells. In addition, colocalization of colloidal gold particles and reaction
      product of NAD(P)H-oxidase in the PV of some activated HUVEC was observed. These
      results suggest that NAD(P)H-oxidase may participate in a mechanism by which IFN
      gamma-activated HUVEC inhibit T. gondii multiplication.

PMID- 16419749
TI  - Genetic complementation to identify DNA elements that influence complement
      resistance in Leishmania chagasi.
AB  - Past studies showed that Leishmania spp. promastigotes exhibit differential
      sensitivity to complement mediated lysis (CML) during development in vitro and in
      vivo. Leishmania chagasi promastigotes in cultures during logarithmic and
      stationary growth phases are CML-sensitive or CML-resistant when exposed to human
      serum, respectively, but only in cultures recently initiated with parasites from
      infected animals; serially passaged cultures become constitutively CML-sensitive
      regardless of growth phase. Building on these observations, a genetic screen was
      conducted to identify novel complement resistance factors of L. chagasi. A cosmid
      library containing genomic DNA was transfected into a promastigote line
      previously subjected to >50 serial passages. Selection with human serum for CML
      resistance yielded 12 transfectant clones. Cosmids isolated from 7 of these
      clones conferred CML resistance when transfected into an independent, high
      passage promastigote culture; at 12% human serum, the mean survival of
      transfectants was 37% (+/- 11.6%), and that of control transfectants was about
      1%. Inserts within the 7 cosmids were unique. Determination of the complete DNA
      sequence for 1 cosmid indicated that its 32-kilobase insert was 89% identical
      (overall) to a 31-kilobase region of Leishmania major chromosome 36, which is
      predicted to encode 6 genes, all of which encode hypothetical proteins.

PMID- 16419750
TI  - Cross-resistance of largemouth bass to glochidia of unionid mussels.
AB  - We tested whether host fish that acquired resistance to glochidia of one mussel
      species were cross-resistant to glochidia of other species. Largemouth bass
      (Micropterus salmoides) were primed with 4-5 successive infections of glochidia
      of Lampsilis reeveiana. The percentage of attached glochidia that survived and
      transformed to the juvenile stage (transformation success) was compared between
      primed fish and naive controls. Transformation success of L. reeveiana, Lampsilis
      abrupta, Villosa iris, and Utterbackia imbecillis was significantly lower on
      primed fish (37.8%, 43.5%, 67.0%, and 13.2%, respectively) than on control fish
      (89.0%, 89.7%, 90.0%, and 22.2% respectively). Immunoblotting was used to analyze
      the binding of serum antibodies from primed fish with glochidia proteins.
      Antibodies bound to glochidia proteins of similar molecular weight from L.
      reeveiana and L. abrupta. Bound proteins of V. iris differed in molecular weight
      from those of the Lampsilis species. There was no binding to specific glochidia
      proteins of U. imbecillis or Strophitus undulatus. Our results indicate that host
      acquired resistance can extend across mussel genera and subfamilies and might
      involve both specific and nonspecific mechanisms. Understanding the specificity
      of acquired resistance of hosts to glochidia could enhance understanding of the
      evolutionary and ecological relationships between mussels and their host fishes.

PMID- 16419751
TI  - A comparison of several serologic tests to detect antibodies to Toxoplasma gondii
      in naturally exposed bottlenose dolphins (Tursiops truncatus).
AB  - Toxoplasma gondii infection in marine mammals is intriguing and indicative of
      contamination of the ocean environment and coastal waters with oocysts. In a
      previous study, 138 of 141 (97.8%) bottlenose dolphins (Tursiops truncatus) from
      the coasts of Florida and California had antibodies to T. gondii by the modified
      agglutination test (MAT). Although the MAT has been found to be highly sensitive
      and specific for T. gondii antibodies from several species of terrestrial
      animals, it has not yet been validated for T. gondii infections in marine
      mammals. Furthermore, T. gondii has yet not been isolated from dolphins. In the
      present study, sera from 146 (60 from the 2004 samples and 86 from the 2003
      samples) T. truncatus from the coastal areas of South Carolina and Florida were
      tested for antibodies to T. gondii. Sera from 2004 were tested by the MAT, the
      indirect fluorescent antibody test (IFAT), the Sabin-Feldman dye test (DT), an
      indirect hemagglutination test (IHAT), an enzyme-linked immunosorbent assay
      (ELISA), and Western blot. All 60 dolphins were seropositive, with MAT titers of
      1:20 in 3, 1:40 in 19, 1:80 in 29, 1:160 in 2, 1:1,280 in 3, 1:2,560 in 2, and
      1:5,120 or higher in 2, and these results were confirmed in another laboratory.
      The DT titers of these dolphins were <1:10 in 53, 1:800 in 3, 1:1,600 in 2, and
      1:3,200 in 2. The IHAT titers were <1:64 in 52, 1:128 in 1, 1:512 in 2, and
      1:2,048 in 5. The IFAT titers were <1:20 in 3, 1:20 in 11, 1:40 in 36, 1:80 in 2,
      1:160 in 1, and 1:320 or higher in 7. All 7 DT-positive dolphins had high MAT
      titers, but 2 were negative by the IHAT. Western blot results closely followed
      MAT results; ELISA results matched MAT results, which were 1:40 or higher. In
      sera from the 2003 samples, MAT antibodies were found in 86 of 86 dolphins with
      titers of 1:25 in 29, 1:50 in 23, 1:100 in 27, 1:200 in 3, 1:1,600 in 1, and
      1:3,200 in 3; these sera were not tested by other means. Overall, MAT antibodies
      were found in all 146 dolphin sera tested. Because marine mammals are considered
      sentinel animals indicative of contamination of the coastal and marine waters by
      T. gondii oocysts, serologically positive infections need to be validated by the
      detection of T. gondii organisms in the tissues of seropositive animals.

PMID- 16419752
TI  - Prevalence of viable Toxoplasma gondii in beef, chicken, and pork from retail
      meat stores in the United States: risk assessment to consumers.
AB  - The prevalence of viable Toxoplasma gondii was determined in 6,282 samples (2,094
      each of beef, chicken, and pork) obtained from 698 retail meat stores from 28
      major geographic areas of the United States. Each sample consisted of a minimum
      of 1 kg of meat purchased from the retail meat case. To detect viable T. gondii,
      meat samples were fed to T. gondii-free cats and feces of cats were examined for
      oocyst shedding. Initially, 100 g of meat from 6 individual samples of a given
      species were pooled (total, 600 g), fed to a cat over a period of 3 days, and
      feces were examined for oocysts for 14 days; the remaining meat samples were
      stored at 4 C for 14 days (until results of the initial cat fecal examination
      were known). When a cat fed pooled samples had shed oocysts, 6 individual meat
      samples from each pool were bioassayed for T. gondii in cats and mice. Toxoplasma
      gondii isolates were then genetically characterized using the SAG2 locus and 5
      hypervariable microsatellite loci. In all, 7 cats fed pooled pork samples shed
      oocysts. Toxoplasma gondii oocysts were detected microscopically in the feces of
      2 of the cats; 1 isolate was Type II and the second was Type III. Analyzed
      individually, T. gondii was detected by bioassay in 3 of the 12 associated
      samples with genetic data indicating T. gondii isolates present in 2. The
      remaining 5 pooled pork samples had so few oocysts that they were not initially
      detected by microscopic examination, but rather by mouse bioassay of cat feces.
      Two were Type I, 1 was Type II, and 2 were Type III. None of the cats fed chicken
      or beef samples shed oocysts. Overall, the prevalence of viable T. gondii in
      retail meat was very low. Nevertheless, consumers, especially pregnant women,
      should be aware that they can acquire T. gondii infection from ingestion of
      undercooked meat, and in particular, pork. Cooking meat to an internal
      temperature of 66 C kills T. gondii.

PMID- 16419754
TI  - Patterns of coccidial prevalence in lizards of Mauritius.
AB  - This paper reports prevalence of coccidial oocysts in fecal samples from 6
      endemic and 2 introduced lizard species on Mauritius, an island nation in the
      Indian Ocean. Total coccidian prevalence was 54% (n = 341) for the endemic
      'ornate day gecko,' Phelsuma ornata; 48% (n = 159) for the endemic 'Durrell's
      night gecko,' Nactus durrelli; 53% (n = 15) for the endemic 'Serpent Island night
      gecko,' N. serpensinsula; and 78% (n = 248) for the introduced gecko,
      Hemidactylus frenatus. These high prevalences may reflect lack of long-lasting
      immune response to coccidial infection. There were few significant differences in
      prevalence among age, island, sex, or body condition within species, suggesting
      that these coccidia are relatively nonpathogenic and have little effect on host
      fitness. Prevalence was higher in the dry season than the wet season. These data
      suggest other factors, such as low host immune response to reinfection, affect
      overall prevalence more significantly than the effect of humidity on oocyst
      survival on Mauritius. No coccidia were found in samples from the endemic
      'Gunner's Quoin night gecko,' N. coindemirensis (n = 155), probably reflecting
      parasite extinction due to a host population bottleneck following historical
      introduction of rats. There was no evidence of competitive or facilitative
      interactions between Eimeria sp. and Isospora sp., but evidence of competition
      between 2 Eimeria species in the 'ornate day gecko,' Phelsuma ornata. No evidence
      was found of cross-species infection, suggesting that reptile coccidia have high
      host specificity and are, therefore, poor subjects for studies of parasite
      mediated competition and the evolution of sex.

PMID- 16419753
TI  - In vitro and in vivo effects of unsaturated fatty acids on Schistosoma mansoni
      and S. haematobium lung-stage larvae.
AB  - Incubation of Schistosoma mansoni lung-stage larvae in 90% corn oil for 6 hr was
      shown to elicit exposure of their, otherwise masked, apical membrane antigens to
      binding of anti-schistosome antibodies in the indirect membrane
      immunofluorescence test (IF). The possibility that unsaturated fatty acids (FA)
      are responsible for this effect was herein supported by IF data on ex vivo lung
      stage larvae of S. mansoni and S. haematobium incubated for 1/2-2 hr with 80%
      corn oil, 50% olive oil, or 10-20 microM arachidonic acid. Treatment with
      unsaturated FA followed by filipin staining for cholesterol visualization
      indicated that unsaturated FA do not induce exposure of schistosomular surface
      membrane antigens via extraction of surface membrane cholesterol. Evidence using
      inhibitors and stimulators of neutral sphingomyelinase suggested that unsaturated
      FA perhaps activate worm tegument-bound neutral sphingomyelinase, leading to
      sphingomyelin hydrolysis and changes in surface membrane fluidity. Larval apical
      membrane antigens are, thus, allowed to diffuse freely in the plane of the
      membrane and bind specific antibodies in IE Excessive sphingomyelin hydrolysis
      might explain why high FA concentrations or long incubation periods eventually
      lead to larval death. The significant decrease (P < 0.01) in S. mansoni and
      increase (P < 0.02) in S. haematobium worm recovery in BALB/c mice given
      unsaturated FA-high and -poor diets, respectively, indicated these findings have
      in vivo relevance and led to the proposal that unsaturated FA likely plays a role
      in natural attrition of S. mansoni and S. haematobium lung-stage larvae.

PMID- 16419755
TI  - Nematode infection in Mugil incilis (Lisa) from Cartagena Bay and Totumo Marsh,
      north of Colombia.
AB  - Nematode infection indices were recorded in Lisa, Mugil incilis, from Cartagena
      Bay and Totumo Marsh, north of Colombia, during an 8-mo period (February to
      September 2002). Parasite prevalence (74.67% vs. 53.48%), intensity (9.73 +/-
      2.98 vs. 2.73 +/- 1.07), and abundance (7.49 +/- 2.21 vs. 2.04 +/- 1.17) were
      significantly greater in Cartagena Bay, an estuary polluted by domestic sewage
      and industrial discharge, compared with those of Totumo Marsh, a body of water
      with low levels of contamination. Parasites were found below the spine, within
      the liver and the intestinal mesenteries, and a small percentage in muscle.
      Morphological analysis of nematodes indicated the presence of the third larval
      stage of several species belonging to the Anisakidae. Size correlated moderately
      and significantly with parasite intensity in fish collected from Totumo Marsh (R
      = 0.336; P < 0.001); in Cartagena Bay the correlation was also significant, but
      low and negative (R = -0.212; P = 0.003), clearly showing differences in host
      parasite ecology. Fish health status, as represented by condition factor and
      hepatosomatic index, did not show any correlation with the parasite prevalence in
      fishes collected in either sampling areas. These results suggest, for the first
      time, that the consumption of Lisa from the Atlantic coast of Colombia could
      represent a risk for human infection.

PMID- 16419756
TI  - Non-sand fly transmission of a North American isolate of Leishmania infantum in
      experimentally infected BALB/c mice.
AB  - Leishmania infantum, an etiologic agent of zoonotic visceral leishmaniasis, is
      endemic in the foxhound population in the United States and Canada. Leishmaniasis
      is usually transmitted by blood-feeding sand flies; however, epidemiological data
      do not support a significant role for sand flies in the maintenance of foxhound
      infections in North America, and an alternate mode of transmission may exist. The
      present study was conducted to determine if transplacental or direct transmission
      occurs in pregnant BALB/c mice experimentally infected with L. infantum isolated
      from a naturally infected foxhound from Virginia as well as to determine if the
      parasite was directly transmitted to the males used to breed the mice. Female
      BALB/c mice were intravenously inoculated with 1 x 10(6) promastigotes of the
      LIVT-1 strain of L. infantum. Mice were bred to uninfected male BALB/c mice 2 mo
      postinoculation. Pregnant mice were killed between days 13 and 18 of gestation.
      Pups and placentas were collected at necropsy, divided, and used for parasite
      culture and polymerase chain reaction (PCR) analyses. Culture and PCR analyses
      were performed on spleens from the male mice to determine the possibility of
      sexual transmission. Leishmania sp. DNA was detected in 4 of 88 pups and 3 of 16
      placentas from LIVT-1-inoculated mice. One male mouse used to breed infected
      females was PCR positive. This work provides evidence for a low level of
      nonvector transmission of North American L. infantum in a mouse model.

PMID- 16419757
TI  - Strongyloides ratti infection in the large intestine of wild rats, Rattus
      norvegicus.
AB  - The large intestine of a rat has been neglected almost completely as a site of
      Strongyloides sp. infection. We reported that adult Strongyloides ratti remained
      in the large intestine for more than 80 days, producing more number of infective
      larvae than small intestine adults, and therefore hypothesized that parasitism in
      this site could be a survival strategy. In wild rats, however, no study has
      focused on large intestine infections of Strongyloides. The present study
      revealed that 32.4% of 68 wild rats, Rattus norvegicus, had the infection of S.
      ratti in the large intestine, with an average of 4.7 worms. These worms harbored
      normal eggs in the uterus. In a laboratory experiment with S. ratti and Wister
      rats, daily output of infective larvae by 4.7 females in the large intestine was
      estimated to be 4,638.4, suggesting that a few parasites could play a role in the
      parasite transmission. Five species of nematode found in the wild rats showed
      seasonality in infection intensity, with highest intensities in March-May. The
      number of S. ratti in the large intestine was also highest in these months.

PMID- 16419758
TI  - The life cycle and pathogenicity of coccicium Eimeria nocens (Kotlan, 1933) in
      domestic goslings.
AB  - Twenty-four 10-day-old, artificially reared, coccidia-free goslings (Anser
      cygnoides var. domestica) were inoculated orally with 1.0x10(5)-1.0x10(6)
      sporulated oocysts of Eimeria nocens, and killed at intervals from 30 to 336 hr
      postinoculation (PI). Parts of the visceral organs, including intestines, kidney,
      liver, gallbladder, and spleen from inoculated goslings, were fixed and
      sectioned. The life cycle of E. nocens and histologic changes during infection
      were examined microscopically. The results showed that at least 3 generations of
      meronts developed in the endogenous stage of the life cycle of E. nocens. Two
      types of meronts were found. The first completed maturation at 54 to 78 hr PI.
      These meronts were the first generation, with each forming about 12 merozoites.
      The second completed maturation at 102 to 240 hr PI. These meronts were the
      second or third generations, with each meront forming about 24 merozoites.
      Development of gamonts began at about 198 hr after infection. The prepatent
      period was 9 days and discharge of oocysts continued for 4 days. Sporulation of
      oocysts occurred in 60-72 hr at 25 C. Eimeria nocens invaded the posterior
      jejunum, ileum, caecum, rectum, and cloaca. Developmental stages were localized
      within the epithelial cells of villi and crypts, and in lamina propria. Marked
      histological changes, including desquamation and necrosis of intestinal
      epithelium, submucosal edema, hemorrhages, infiltration of inflammatory cells,
      and villous atrophy, were seen during the periods of late merogony, gamogony, and
      oocyst shedding. They were most pronounced in the ileum and the regions nearby.
      The infected goslings showed severe diarrhea, bloody feces, anorexia, emaciation,
      and even death, suggesting that E. nocens is highly pathogenic for goslings.

PMID- 16419760
TI  - Two multivalvulid myxozoans causing postmortem myoliquefaction: Kudoa megacapsula
      n. sp. from red barracuda (Sphyraena pinguis) and Kudoa thyrsites from splendid
      alfonso (Beryx splendens).
AB  - Postmortem myoliquefaction associated with multivalvulid myxozoans was found in
      fillets of red barracuda (Sphyraena pinguis) and splendid alfonso (Beryx
      splendens), which were imported to Japan from China and South Africa,
      respectively. Morphological examinations of the myxozoans from the somatic muscle
      of red barracuda revealed that spores (30.3-44.7 microm in maximum thickness) had
      4 distinct winglike valves, in which 1 extremely large (12.7 x 5.8 microm), 2
      small, and 1 vestigial polar capsule were present. The small subunit ribosomal
      DNA sequence analysis showed that the myxozoan cluster within a clade was
      composed of Kudoa thyrsites, Kudoa minithyrsites, and Kudoa lateolabracis, all
      having stellate spores with 1 polar capsule larger than the other 3. On the basis
      of these characteristics, we describe this parasite as Kudoa megacapsula n. sp.
      Morphological and molecular analyses of the myxozoan from splendid alfonso
      identified it as K. thyrsites, which has been described from many marine fishes.
      To our knowledge, this is the first record of K. thyrsites in splendid alfonso.

PMID- 16419759
TI  - Differences in Hsp70 expression in the sporozoites of the original strain and
      precocious lines of Eimeria tenella.
AB  - The levels of expression of Heat shock protein 70 (Hsp 70) in sporozoites of a
      wild-type parent strain and 2 precocious lines of Eimeria tenella, were compared
      to investigate the relationship between the heat shock proteins expressed by the
      parasite and virulence of the strain. Hsp70 expression was analyzed in
      sporozoites by immunohistochemical techniques, immunoblot, and flow cytometric
      analyses. One band of 70 kDa was identified and the variation of the Hsp70
      expression levels was quantified by optical densitometric analyses. The results
      showed a significant gradual decrease in the Hsp70 expression in sporozoites of
      E. tenella as attenuation progressed, suggesting that the Hsp70 expressed in the
      excysted sporozoites of E. tenella might be involved in parasite pathogenicity.
      In addition, the cytoplasmic distribution of the Hsp70, which was observed in the
      entire sporozoites of the wild strain, was reduced to the anterior portion in the
      precocious lines.

PMID- 16419761
TI  - Multivalvulid myxozoans from eastern Australia: three new species of Kudoa from
      scombrid and labrid fishes of the Great Barrier Reef, Queensland, Australia.
AB  - Three new species of Kudoa, each having 6 polar capsules, are described from the
      somatic muscle of fishes collected on the Great Barrier Reef, Queensland,
      Australia. Kudoa grammatorcyni n. sp. was observed in the shark mackerel
      Grammatorcynus bicarinatus. Spores are stellate in apical view, width (all
      measurements in microm) 8.62 (8.03-8.95); thickness 8.14 (7.63-8.68); suture
      width 7.7 (7.24-8.16); length 6.54 (6.32-6.71); polar capsule length 3.68 (3.55
      3.82); polar capsule width 1.72 (1.65-1.84). Kudoa scomberomori n. sp. is
      described from the Spanish mackerel Scomberomorus commerson. Spores are stellate
      in apical view, width 7.56 (6.84-8.16); thickness 6.79 (6.18-7.63); suture width
      5.92 (5.26-6.32); length 5.43 (5.00-6.18); polar capsule length 3.24 (3.03-3.55);
      polar capsule width 1.37 (1.25-1.51). Kudoa thalassomi n. sp. is described from
      the moon wrasse Thalassoma lunare. Spores are stellate in apical view, width
      10.66 (9.47-11.84); thickness 9.37 (8.55-10.79); suture width 7.98 (6.84-8.82);
      length 6.65 (6.18-7.11); polar capsule length 4.92 (4.74-5.00); polar capsule
      width 2.12 (2.04-2.24). All 3 species differ in spore morphology from the 1
      previously described myxozoan with 6 polar capsules, Hexacapsula neothunni from
      yellowfin tuna Neothunnus macropterus, which has since been reassigned to Kudoa.

PMID- 16419762
TI  - A new species of Gnathostoma (Nematoda: Gnathostomatidae) in Procyon lotor
      hernandezii from Mexico.
AB  - Gnathostoma lamothei n. sp., inhabiting the stomach of Procyon lotor hernandezii
      Wagler, 1831, in Tlacotalpan, Veracruz State, and Rio Sapo, Oaxaca, Mexico, is
      described. This new species differs from all other congeners by having the
      posterior half of the body surface covered by rows of tiny round bosses instead
      of spines, or lacking ornamentations. Sequences of the ITS2 of the ribosomal DNA
      of G. lamothei n. sp. are compared with sequences of other species of the genus
      recorded in Mexico; they show a wide divergence (<50%) with Gnathostoma
      binucleatum Almeyda-Artigas, 1991, and Gnathostoma turgidum Stossich, 1902, and
      high similarity with Gnathostoma sp. I sequence (99.2%). On the basis of
      morphometric traits and sequences, previous records of Gnathostoma sp. I
      (=Gnathostoma procyonis of Almeyda-Artigas et al., 1994, not Chandler, 1942, and
      Gnathostoma neoprocyonis nomen nudem) in Mexico are referred to as the new
      species.

PMID- 16419763
TI  - New species of Falcaustra (Nematoda: Kathlaniidae) from Heosemys grandis
      (Testudines: Emydidae).
AB  - Falcaustra kinsellai n. sp. from the intestines of the turtle Heosemys grandis is
      described and illustrated. Falcaustra kinsellai represents the 30th Oriental
      species assigned to the genus and is distinguished from other species by the
      distribution pattern of caudal papillae (6 precloacal, 6 adcloacal, 10
      postcloacal, and 1 median), length of spicules (427-451 microm), presence of a
      pseudosucker, and presence of a toothed chamber between vestibule and pharynx.

PMID- 16419764
TI  - A revision of Phoreiobothrium (Tetraphyllidea: Onchobothriidae) with descriptions
      of five new species.
AB  - Five new species of Phoreiobothrium (Cestoda: Tetraphyllidea) are described from
      carcharhiniform sharks collected from a diversity of localities throughout the
      world. These are Phoreiobothrium perilocrocodilus n. sp. from Negaprion
      acutidens, Phoreiobothrium anticaporum n. sp. from Negaprion brevirostris,
      Phoreiobothrium lewinense n. sp. from Sphyrna lewini, Phoreiobothrium robertsoni
      n. sp. from Carcharhinus brachyurus, and Phoreiobothrium blissorum n. sp. from C.
      plumbeus, This brings the number of described species of Phoreiobothrium to 17.
      The new species from the lemon sharks, P. perilocrocodilus n. sp. and P.
      anticaporum n. sp., both possess more bothridial subloculi than do all species
      from hammerhead sharks, and fewer subloculi than do all species from sharks of
      Carcharhinus spp. Phoreiobothrium anticaporum n. sp. is unique among
      Phoreiobothrium species in that its genital pore is located in the extreme
      anterior portion of the proglottid. Phoreiobothrium lewinense n. sp. is unique in
      its possession of a combination of 8-11 subloculi and basal hook prongs that lack
      internal channels. Phoreiobothrium robertsoni n. sp. possesses 25-29 subloculi,
      triangular bothridia that flare posteriorly, and hooks that extend well beyond
      the middle of the bothridia. Phoreiobothrium blissorum n. sp. is most similar to
      Phoreiobothrium lasium in that it possesses rectangular bothridia with greater
      than 22 subloculi and long filitriches on its scolex. However, it differs from
      the latter species in that rather than articulating with one another, the bases
      of the medial and lateral hooks are widely separated; it also possesses 5-6 (vs.)
      7-8 columns of testes. Phoreiobothrium lasium and Phoreiobothrium tiburonis are
      redescribed. The host associations of P. lasium are reevaluated and a neotype is
      designated for this species. The mature proglottid of P. tiburonis is described
      for the first time from voucher material collected from the type host and
      locality. These data suggest that the proglottid information provided in the
      original description, which was obtained from detached gravid proglottids, may
      have come from a tapeworm species other than P. tiburonis. All 7 species treated
      here in detail were examined with scanning electron microscopy; most were found
      to exhibit a microthrix pattern similar to that described previously for other
      members of the genus, e.g., Phoreiobothrium manirei. Bladelike spinitriches were
      present on the strobila, cephalic peduncle, and proximal bothridial surfaces, but
      were lacking from the distal bothridial surfaces. These spinitriches varied in
      length and density among species. Filitriches were present on all of these
      surfaces, but varied somewhat in length among species. Phoreiobothrium lewinense
      n. sp. is exceptional in that spinitriches were not seen on the proximal
      bothridial surfaces. A key to Phoreiobothrium species is provided. This work
      brings the number of carcharhinid shark species known to host this onchobothriid
      genus to 6, and the number of sphyrnid species to 5. Like many other
      onchobothriid tapeworms, species of Phoreiobothrium appear to exhibit oioxenous
      specificity for their hosts. Given this, and the fact that a total of 9 genera
      and 46 species of carcharhinid and sphyrnid sharks have yet to be examined for
      Phoreiobothrium, the diversity of the genus globally is likely to greatly exceed
      that described to date.

PMID- 16419765
TI  - Kudoa iwatai (Myxosporea: Multivalvulida) in wild and cultured fish in the Red
      Sea: redescription and molecular phylogeny.
AB  - Gilt-head sea bream, Sparus aurata L., the Mediterranean's most important
      mariculture species, has been cultured for the last 30 yr in Eilat (Israeli Red
      Sea). Kudoa sp. was the first myxosporean parasite reported from this species. In
      recent years, an increase in prevalence in both land-based and sea-cage
      facilities in Eilat has been observed. Infections with the same Kudoa species
      appeared in cultured European sea bass Dicentrarchus labrax (L.) and grey mullet
      Mugil cephalus in the same farms, as well as in 10 species of wild Red Sea reef
      fish, indicating that Kudoa sp. is not fastidious with regard to its host. All
      affected species displayed 1- to 2-mm (up to 5 mm) whitish, spherical, or oval
      polysporous plasmodia. The parasite established multiple site infections, most
      commonly in the muscles and intracranial adipose tissue of the brain and eye
      periphery. Other sites were subcutaneous adipose tissue, nerve axons, mouth, eye,
      mesenteries, peritoneum, swim bladder, intestinal musculature, heart,
      pericardium, kidney, and ovary. On the basis of spore morphology, the parasite
      was identified as Kudoa iwatai Egusa and Shiomitsu, 1983. Ultrastructural
      features were comparable to those of previously studied Kudoa species. The 18S
      rDNA from 7 Red Sea isolates was sequenced and compared with the sequence of the
      same gene from K. iwatai isolated from cultured red sea bream, Pagrus major, in
      Japan. The phylogenetic position of K. iwatai within the genus was determined
      using sequence analysis of all related taxa available in GenBank. The 3 isolates
      of K. iwatai clustered together on a newly formed, highly supported clade. The
      Red Sea strain of K. iwatai is apparently native to the region. In the absence of
      records of this Kudoa sp. from the extensive Mediterranean sea bream and sea bass
      production industries, introduction with its Mediterranean hosts seems unlikely.
      Therefore, we conclude that K. iwatai is an Indo-Pacific species that, in the Red
      Sea, has extended its host range to include the allochthonous gilt-head sea
      bream, European sea bass, and grey mullet.

PMID- 16419766
TI  - Scuticociliate endosymbionts of echinoids (phylum Echinodermata): phylogenetic
      relationships among species in the genera Entodiscus, Plagiopyliella,
      Thyrophylax, and Entorhipidium (phylum Ciliophora).
AB  - Morphological research on over 50 species of ciliates recorded as endosymbionts
      of echinoids suggests that invasion of the echinoid microhabitat occurred on at
      least 4 occasions. Gene sequence data confirm the phylogenetic distinctness of
      spirotrichean, armophorean, plagiopylean, and oligohymenophorean endosymbionts.
      It is also likely that oligohymenophoreans have repeatedly invaded the gut
      habitat. To test this hypothesis, we sequenced small subunit rRNA (SSrRNA) genes
      of 6 species representing the larger scuticociliate species found in the
      intestine of Strongylocentrotus pallidus from the northeast Pacific Ocean:
      Entodiscus borealis (Entodiscidae); Plagiopyliella pacifica and Thyrophylax vorax
      (Thyrophylacidae); and Entorhipidium pilatum, Entorhipidium tenue, and
      Entorhipidium sp. (Entorhipidiidae). SsrRNA genes were amplified by PCR, and
      sequences obtained in both directions. In all phylogenetic analyses, the
      scuticociliates are well supported as a clade. Entodiscus is distinct from these
      other echinoid taxa and is the sister taxon to the facultatively parasitic
      Uronema marinum. The other 5 echinoid species always form a clade whose basal
      species is the free-living Parauronema longum. The greatest genetic distance
      among these latter 5 species is less than 1.5%. This probably explains why the
      Thyrophylacidae and Entorhipidiidae are paraphyletic based on the SSrRNA gene
      sequences.

PMID- 16419767
TI  - Three new species of Eimeria (Apicomplexa: Eimeriidae) from the silvery mole rat
      Heliophobius argenteocinereus Peters, 1846 (Rodentia: Bathyergidae) from Malawi.
AB  - Three species of Eimeria Schneider are described from feces of the African
      bathyergid rodent, Heliophobius argenteocinereus, from Malawi. Oocysts of Eimeria
      heliophobii n. sp. are broadly ellipsoidal; 27.9 (22-31) x 22.3 (18-24.5) microm
      with a brownish, heavily pitted oocyst wall, and vacuolar oocyst residuum.
      Sporocysts are oval, 12.8 (12-14) x 8.4 (8-9) microm with Stieda and substieda
      bodies. Eimeria nafuko n. sp. has subspherical oocysts; 15.5 (15-16) x 12.8 (12
      13) microm with a smooth, colorless oocyst wall. Sporocysts are oval, 9.2 (9-10)
      x 5.3 (5-6) microm, with a small Stieda body; the substieda body is not visible.
      Oocysts of Eimeria yamikamiae n. sp. are broadly ellipsoidal to subspherical;
      20.8 (19-22) x 17.5 (15.5-19) microm, with slightly yellowish, very faintly
      pitted oocyst wall. The majority of oocysts contained a single spherical
      vesicular oocyst residuum and numerous very small granules. Sporocysts are oval,
      10.7 (10-11) x 6.8. (6-7) microm, with a dome -like Stieda body and a
      subspherical to lentil-like substieda body. Typically, infected rodents shed
      oocysts of more than 1 species of Eimeria.

PMID- 16419768
TI  - Description of Dendrorchis retrobiloba n. sp. (Digenea: Gorgoderidae) from
      Astyanax fasciatus (Teleostei: Characidae) from Southern Uruguay, with an emended
      diagnosis of the genus Dendrorchis.
AB  - To date, the monospecific Dendrorchis is represented by D. neivai, reported from
      Brazil and parasitizing Brycon lundi. Dendrorchis retrobiloba n. sp. is described
      from the swim bladder of Astyanax fasciatus from Canada del Dragon stream in
      Montevideo, southern Uruguay (34 degrees 47'S, 56 degrees 14'W), and the emended
      diagnosis of Dendrorchis is given. The diagnosis of Dendrorchis has been modified
      to include the following characters: Phyllodistominae with flattened body, wider
      in the region posterior to acetabulum. Intestinal ceca sinuous or not. Testes
      branched or with superficial lobes. Ovary with deep or superficial lobes. Seminal
      receptacle present or absent. Vitellaria ellongate or pyriform. Uterus extends to
      posterior region and to portion of body anterior to acetabulum. Eggs oval,
      variable size, thin-shelled, without opercula. Dendrorchis retrobiloba n. sp.
      differs from D. neivai by having pyriform vitellaria, ovary larger than the
      testes and not deeply lobed, wider distribution of the uterus, smaller egg size,
      testes with superficial lobes, oral sucker wider than the acetabulum, shorter
      esophagus, 2 terminal lobes at the posterior end of the body, and much smaller
      body length. Despite being found in different hosts, both species of Dendrorchis
      parasitize the swim bladder of freshwater Characidae.

PMID- 16419769
TI  - Cutaneous leishmaniasis: evaluation by polymerase chain reaction in the Cukurova
      region of Turkey.
AB  - The diagnosis of cutaneous leishmaniasis (CL) may depend on the detection of the
      parasite in histologic sections, the growth of the promastigotes in culture, or
      the identification of parasite by other techniques. We performed polymerase chain
      reaction (PCR) on paraffin-embedded biopsies to determine the validity of this
      technique for diagnosis of CL. PCR was used to detect the parasite using 2
      different DNA extraction methods. PCR was positive in all 20 cases when the
      Leishmania parasite was detected by light microscopy. Twenty-seven of 34 cases
      that were negative microscopically for the parasite were positive using PCR. The
      first extraction method of DNA identified leishmanial DNA in 41 of 54 cases
      (75.9%); the second extraction of DNA was positive in 47 of 54 cases (87%). PCR
      was negative in all of the nonleishmaniasis cases. The PCR-based method appears
      to be a useful diagnostic approach for identification of suspected cases of CL.

PMID- 16419770
TI  - Evaluation of homologous, heterologous, and affinity conjugates for the
      serodiagnosis of Toxoplasma gondii and Neospora caninum in maned wolves
      (Chrysocyon brachyurus).
AB  - Use of serological tests in the diagnosis of infectious diseases in wild animals
      has several limitations, primarily the difficulty of obtaining species-specific
      reagents. Wild canids, such as maned wolves (Chrysocyon brachyurus), are highly
      predisposed to infection by Toxoplasma gondii and, to a lesser extent, to
      Neospora caninum. The aim of the present study was to evaluate homologous,
      heterologous, and affinity conjugates in enzyme-linked immunosorbent assays
      (ELISAs) and indirect fluorescent antibody tests (IFATs) for detecting
      immunoglobulin (Ig) G antibodies against T. gondii and N. caninum in maned
      wolves. Serum samples were obtained from 59 captive animals in Brazil and tested
      by ELISA for T. gondii serology and IFAT for N. caninum serology using 3
      different enzymatic and fluorescent conjugates: homologous (guinea pig anti-maned
      wolf IgG-peroxidase and -fluorescein isothiocyanate [FITC]), heterologous (rabbit
      anti-dog IgG-peroxidase and -FITC), and affinity (protein A-peroxidase and 
      FITC). Seropositivity to T. gondii was comparable among the homologous (69.5%),
      heterologous (74.6%), and affinity (71.2%) enzymatic conjugates. A significant
      positive correlation was found between the antibody levels determined by the 3
      enzymatic conjugates. The highest mean antibody levels (ELISA index = 4.5) were
      observed with the protein A-peroxidase conjugate. The same seropositivity to N.
      caninum (8.5%) was found with the homologous and heterologous fluorescent
      conjugates, but protein A-FITC was not able to detect or confirm any positive
      samples with homologous or heterologous conjugates. Our results demonstrate that
      homologous, heterologous, and affinity conjugates might be used in ELISA for
      serological assays of T. gondii in wild canids, whereas for N. caninum infection,
      only the homologous or heterologous fluorescent conjugates have been shown to be
      useful.

PMID- 16419771
TI  - Prevalence of antibodies to Neospora caninum in wild animals.
AB  - Antibodies to Neospora caninum were determined in several species of wild animals
      in the United States by the Neospora agglutination test (NAT). Antibodies (NAT
      1:40 or higher) were found in 5 of 249 bison (Bison bison), 5 of 160 caribou
      (Rangifer tarandus), 4 of 162 moose (Alces alces), 4 of 122 wolves (Canis lupus),
      and 1 of 224 musk ox (Ovibos moschatus) but not in 197 black bears (Ursus
      americanus). To our knowledge, this is the first report of antibodies to N.
      caninum in bison and caribou. The total absence of N. caninum antibodies in black
      bears indicates that bears are not a host for N. caninum and that there is no
      cross-reactivity between the NAT and the modified agglutination test (MAT) for
      Toxoplasma gondii, because more than 80% of black bears in eastern United States
      have MAT antibodies at a 1:25 serum solution.

PMID- 16419772
TI  - Ultrastructure of contact-chemoreceptor sensilla found among the genae of female
      Gasterophilus nasalis.
AB  - Scanning electron microscopy was used to observe contact-chemoreceptor sensilla
      in the genae of the anterior vestigial mouthparts of female Gasterophilus
      nasalis. These were of the uniporous trichoid type and were surrounded by
      mechanosensory aporous trichoid sensilla of variable size. Contact-chemoreceptor
      sensilla could be involved in detecting different chemical substances, including
      the equine kairomones that stimulate females to lay eggs on the hair of the host
      and/or the short-range sexual pheromones used in precopulatory courtship. The
      probable functions of these sensilla are discussed with reference to the current
      literature on the sensorial organs of muscomorphid dipterans.

PMID- 16419773
TI  - Age of adult worms of Echinostoma caproni does not affect development of
      miracidia.
AB  - The effect of the age of adult Echinostoma caproni on egg development was
      studied. The percentage of fully developed miracidia was determined in eggs
      derived from adult worms obtained from laboratory mice at 2, 4, 6, and 8 wk
      postinfection (PI). Regardless of the age of worms from which the eggs were
      obtained, the percentage of fully developed miracidia was always >90%, and 60-80%
      of the eggs hatched. Several previous studies have shown that eggs derived from 2
      to 4-wk-old E. caproni yielded miracidia that infected Biomphalaria glabrata
      snails. Results of the present study on E. caproni were in marked contrast to
      previous results with Echinostoma friedi, for which viable eggs were not obtained
      at 2 and 3 wk PI and maximal infectivity of miracidia in snails was obtained from
      eggs derived from worms collected at 8 and 9 wk PI. Further studies are needed to
      determine if the egg viability of other species in the "revolutum" group follow
      that of E. caproni or E. friedi.

PMID- 16419774
TI  - The influence of host sex on the L3 to L4 molt of Brugia malayi.
AB  - Immunocompetent male mice are more susceptible to experimental infection with
      Brugia spp. than are females. Because permissive male SCID mice (severe combined
      immunodeficient mice), which lack T and B cells, also possess higher worm
      burdens, the mechanism is not solely immune mediated. Recovery of fewer adult
      worms from the female SCID mouse suggests that females do not provide sufficient
      nutrients for larval growth. This study assessed the potential of the female SCID
      mouse to support the L3 to L4 molt of Brugia malayi. Unexpectedly, worms grown in
      females molted at earlier time points of recovery than those harvested from
      males. This suggests that the early stage of development of B. malayi is delayed
      in the male murine host. To determine whether the effect of host sex on molting
      may be similar in humans, worms were cultured in media supplemented with serum
      from male or female donors. Worms grown in serum obtained from female donors
      exhibited a significantly higher percentage of complete molts over those cultured
      with serum from males. Host-derived molecules required for the L3 to L4 molt may
      be more abundant in the female, perhaps allowing the worms to survive a
      vulnerable developmental stage in a less permissive environment.

PMID- 16419775
TI  - Prevalence of Cryptosporidium spp. and Giardia spp. in five marine mammal
      species.
AB  - Cryptosporidium spp. and Giardia spp. are protozoan parasites that are often
      associated with severe diarrheal disease in a variety of mammals. Although these
      parasites have been extensively studied in terrestrial ecosystems, little is
      known about either parasite in the marine environment. Therefore, the objective
      of this study was to determine the prevalence of both Cryptosporidium spp. and
      Giardia spp. in 5 marine mammal species. Fecal samples were collected from 39
      bowhead whales (Balaena mysticetus), 49 North Atlantic right whales (Eubalaena
      glacialis), 31 ringed seals (Phoca hispida), 22 bearded seals (Erignathus
      barbatus), and 18 beluga whales (Delphinapterus leucas) between 1998 and 2003.
      Using an immunofluorescent assay, parasites were detected in the feces of bowhead
      whales, right whales, and ringed seals, while neither parasite was detected in
      samples from bearded seals or beluga whales. Overall, prevalences were highest in
      ringed seals (Cryptosporidium spp., 22.6%; Giardia spp., 64.5%) and right whales
      (Cryptosporidium spp., 24.5%; Giardia spp., 71.4%) and lowest in bowhead whales
      (Cryptosporidium spp., 5.1%; Giardia spp., 33.3%). To our knowledge, this is the
      first report of Cryptosporidium spp. and Giardia spp. in either whale species and
      of Cryptosporidium spp. in the ringed seal.

PMID- 16419776
TI  - Prevalence of agglutinating antibodies to Toxoplasma gondii and Sarcocystis
      neurona in beavers (Castor canadensis) from Massachusetts.
AB  - The present study examined the seroprevalence of Toxoplasma gondii and
      Sarcocystis neurona in a population of beavers (Castor canadensis) from
      Massachusetts. Sixty-two blood samples were collected during the field seasons
      over 3 consecutive years from different animals. Blood was collected onto filter
      paper and shipped to the Department of Biomedical Sciences, Virginia Tech,
      Blacksburg, Virginia, for parasite testing. The samples were tested at dilutions
      of 1:25, 1:50, and 1:100 against each parasite antigen by modified agglutination
      tests to determine whether antibodies to either parasite were present in the
      blood. Six of 62 samples (10%) were positive for T. gondii, with 2 samples having
      titers of 1:25 and 4 having titers of 1:50. Four of 62 samples (6%) were positive
      for S. neurona, with 2 samples having titers of 1:25 and 2 having titers of 1:50.

PMID- 16419777
TI  - Prevalence and influence of Loma branchialis (Microspora) on growth and mortality
      in Atlantic cod (Gadus morhua) in coastal Newfoundland.
AB  - A study was conducted to determine the prevalence, geographical distribution, and
      effects of a microsporan parasite, Loma branchialis, in Atlantic cod in coastal
      Newfoundland. The parasite was identified microscopically as opaque, ovoid
      xenomas, primarily in the gills, heart, and spleen. Although widely distributed
      in young fish inhabiting 7 coastal localities, prevalence was 1-7% in general,
      <0.01% in older and large fish, but 78% in market-size cod from a commercial
      farm. Some of the latter fish were emaciated, and approximately 2 mo after the
      parasite was detected, 63% succumbed with a massive infection. Condition factor
      and blood values were significantly lower than those in reference fish. An
      experimental study conducted over 2 yr revealed that mass gained and condition
      factor were significantly lower in infected cod than in controls at the
      termination of the study. Feed consumption, mass gained, feed conversion
      efficiency, and condition factor also were significantly lower in another group
      of infected cod of marketable size studied over 12 wk. Xenomas also were observed
      in the heart and gills of year class II cod reared in a hatchery. Loma
      branchialis is considered to be a potential pathogen in both hatchery-reared and
      net pen-cultured cod in Newfoundland.

PMID- 16419778
TI  - Detection of interspecific competition in parasite communities.
AB  - Matrices of correlation coefficients between the abundances or intensities of all
      pairs of helminth species, across all individual hosts in a sample, are regularly
      used to detect possible cases of interspecific competition in parasite
      communities. In these matrices, however, the range of possible values that any
      correlation coefficient can take is not -1 to 1, contrary to what is generally
      assumed. The number and magnitude of other correlation coefficients in a matrix
      will constrain the values that any given correlation can achieve. This property
      of matrices, and of inter-related natural variables, is explained and illustrated
      with 2 examples from real helminth communities. As a rule, the presence of many
      negative correlations in a matrix raises the lower value that any of them can
      possibly achieve. This has important but previously overlooked implications for
      the interpretation of correlation coefficients, and the detection of competition
      in natural parasite communities.

PMID- 16419779
TI  - The first record of Dirofilaria immitis infection in a Humboldt penguin,
      Spheniscus humboldti.
AB  - Dirofilaria immitis infection is an important parastic disease in many mammals,
      especially canids, but has not been reported in bird hosts. Filarial worms were
      isolated from the lumen of the right atrium of the heart and the connective
      tissue of the lung of a captive female Humboldt penguin, Spheniscus humboldti,
      that died at a zoo in Japan. One of these worms was observed morphologically and
      identified as D. immitis by features such as 4 pairs of cephalic papillae, 1 pair
      of cervical papillae, esophagus divided into 2 regions, 4 pairs of pre-anal
      papillae, 5 pairs of post-anal papillae, and unequal spicules. In addition, the
      partial DNA sequence (234 bp) of mitochondrial CO / gene of the filarial worm was
      identical to that of D. immitis. This is the first report of D. immitis infection
      in a bird.

PMID- 16419780
TI  - Magnetic resonance imaging findings in the brains of rabbits infected with
      Angiostrongylus cantonensis: a long-term investigation.
AB  - Because magnetic resonance (MRI) imaging is a superior technique in delineating
      pathological changes in cerebral angiostrongyliasis, it should also be an optimal
      imaging modality in monitoring long-term changes in the brains of animals
      infected with Angiostrongylus cantonensis. In this study, MRI and histological
      techniques were used to observe the changes in the brains of 7 rabbits infected
      with the third-stage larvae of A. canronensis. Changes were monitored by MRI from
      day 0 to day 207 postinfection (PI). Hyperintense lesions on T2-weighted MR brain
      images were first observed on day 22 PI and hallmarks of abnormalities were noted
      on day 35 PI. Hyperintensities on brain MR images remained up to day 207 PI.
      Histological examination from days 108 to 207 PI revealed meningeal congestion,
      choroid plexus inflammation, infarction, granuloma with embedded larva, gliosis,
      and hemorrhage in the brain tissues. These findings suggest that hosts infected
      with A. cantonensis may undergo pathological changes in the brain tissues for
      more than 200 days PI. Moreover, severe abnormalities may occur as early as the
      fifth week PI.

PMID- 16419781
TI  - Response of T lymphocytes from previously infected calves to recombinant
      Cryptosporidium parvum P23 vaccine antigen.
AB  - We had previously demonstrated that a Type-1-like immune response involving
      interferon-gamma expression in lamina propria lymphocytes accompanied by IgG2
      subclass fecal antibodies to Cryptosporidium parvum p23 emerged in gut mucosa of
      calves recovering from cryptosporidiosis. Because a recombinant p23 had been
      shown to protect calves from cryptosporidiosis when administered as a vaccine
      antigen to late gestation cattle, this study was undertaken to determine if the
      same vaccine antigen could induce a Type-1-like, in vitro response by T cells
      from calves that had recovered from C. parvum infection. We isolated peripheral
      blood mononuclear cells from calves that had been previously infected with C.
      parvum oocysts and incubated them in the presence or absence of the recombinant
      C. parvum p23 vaccine antigen. We used flow cytometry to simultaneously detect
      cells in cell cycle and identify the T cell subset containing cycling cells. We
      also used flow cytometry to identify interferon-gamma positive cells and 2
      dimensional gel electrophoresis to profile proteins made by PBMC stimulated with
      the recombinant p23 vaccine antigen. The results demonstrated that CD4+ T
      lymphocytes proliferated and that interferon-gamma was synthesized by a subset of
      stimulated cells. Two-dimensional gel electrophoresis revealed the presence of
      several cytoplasmic proteins in a size range of approximately 25-80 kDa that were
      detected in p23-stimulated, but not in unstimulated, cytoplasmic samples.
      Together, the results show that the recombinant p23 vaccine antigen can stimulate
      a Type-1-like immune response by T cells from calves that have recovered from C.
      parvum infection.

PMID- 16419782
TI  - Three rarely reported digeneans inhabiting amphibians from Vancouver Island,
      British Columbia, Canada.
AB  - Three rarely reported species of digeneans were collected in amphibian hosts from
      Diversion Reservoir, Sooke, Vancouver Island, British Columbia, Canada. The
      endangered anuran Rana aurora hosted Glypthelmins californiensis, Gorgoderina
      multilobata, and Megalodiscus microphagus. In addition, the anuran Pseudacris
      regilla and the caudatan Taricha granulosa hosted Megalodiscus microphagus.
      Gorgoderina multilobata has been reported only once since 1936 and has never been
      reported outside of California. We note several characters not previously
      reported for Gorgoderina multilobata and G. aurora.

PMID- 16419786
TI  - Click production during breathing in a sperm whale (Physeter macrocephalus).
AB  - A sperm whale (Physeter macrocephalus) was observed at the surface with above-
      and underwater video and synchronized underwater sound recordings. During seven
      instances the whale ventilated its lungs while clicking. From this observation it
      is inferred that click production is achieved by pressurizing air in the right
      nasal passage, pneumatically disconnected from the lungs and the left nasal
      passage, and that air flows anterior through the phonic lips into the distal air
      sac. The capability of breathing and clicking at the same time is unique among
      studied odontocetes and relates to the extreme asymmetry of the sperm whale sound
      producing forehead.

PMID- 16419783
TI  - Acne and your pediatric patient: a roundtable discussion of treatment modalities
      and other factors.

PMID- 16419793
TI  - Measuring the phase of vibration of spheres in a viscoelastic medium as an image
      contrast modality.
AB  - Detection of calcifications in breast is an important problem in the diagnosis of
      breast cancer. Vibro-acoustography is a recently developed method that uses the
      radiation force of ultrasound to create images of the mechanical response of an
      object at a low frequency using the magnitude or phase of the response. Small
      spheres are used to explore the use of the phase of vibration as a contrast
      modality for use in detection and identification of calcifications in breast
      tissue. An experiment is presented to measure the magnitude and phase of
      vibration at different frequencies. The theoretical and experimental results are
      compared for spheres of two different sizes. Phase images are shown in which five
      spheres of different density can be clearly distinguished from each other. With
      phase measurements and images, it is demonstrated that predictable image contrast
      exists for spheres of different density embedded in a viscoelastic medium.

PMID- 16419796
TI  - Two-dimensional numerical simulation of acoustic wave phase conjugation in
      magnetostrictive elastic media.
AB  - The effect of parametric wave phase conjugation (WPC) in application to
      ultrasound or acoustic waves in magnetostrictive solids has been addressed
      numerically by Ben Khelil et al. [J. Acoust. Soc. Am. 109, 75-83 (2001)] using 1
      D unsteady formulation. Here the numerical method presented by Voinovich et al.
      [Shock waves 13(3), 221-230 (2003)] extends the analysis to the 2-D effects. The
      employed model describes universally elastic solids and liquids. A source term
      similar to Ben Khelil et al.'s accounts for the coupling between deformation and
      magnetostriction due to external periodic magnetic field. The compatibility
      between the isotropic constitutive law of the medium and the model of
      magnetostriction has been considered. Supplementary to the 1-D simulations, the
      present model involves longitudinal/transversal mode conversion at the sample
      boundaries and separate magnetic field coupling with dilatation and shear stress.
      The influence of those factors in a 2-D geometry on the potential output of a
      magneto-elastic wave phase conjugator is analyzed in this paper. The process
      under study includes propagation of a wave burst of a given frequency from a
      point source in a liquid into the active solid, amplification of the waves due to
      parametric resonance, and formation of time-reversed waves, their radiation into
      liquid, and focusing. The considered subject is particularly important for
      ultrasonic applications in acoustic imaging, nondestructive testing, or medical
      diagnostics and therapy.

PMID- 16419803
TI  - Three-dimensional passive acoustic tracking of sperm whales (Physeter
      macrocephalus) in ray-refracting environments.
AB  - A wide-aperture towed passive acoustic array is used to obtain ranges and depths
      of acoustically active sperm whales in the Gulf of Mexico in June 2004, by
      extending a technique previously reported [Thode, J. Acoust. Soc. Am. 116, 245
      253 (2004)] to explicitly account for ray-refraction effects arising from a depth
      dependent sound speed profile. Under this expanded approach, three quantities are
      measured from an impulsive sound: the time difference between direct-path
      arrivals on a forward and rear subarray, the time difference between the direct
      and surface-reflected paths on the rear subarray, and the acoustic bearing
      measured on the rear subarray. These quantities, combined with independent
      measurements of hydrophone depths and cable inclination, are converted into range
      depth position fixes by implementing an efficient numerical procedure that uses a
      ray-tracing code to account for ray-refraction effects caused by depth-dependent
      sound speed profiles. Analytic expressions that assume a constant waterborne
      sound speed are also derived. Foraging depths of various sperm whales over 10
      days in June, 2004 are estimated using the numerical technique.

PMID- 16419805
TI  - A model for the dynamics of gas bubbles in soft tissue.
AB  - Understanding the behavior of cavitation bubbles driven by ultrasonic fields is
      an important problem in biomedical acoustics. Keller-Miksis equation, which can
      account for the large amplitude oscillations of bubbles, is rederived in this
      paper and combined with a viscoelastic model to account for the strain-stress
      relation. The viscoelastic model used in this study is the Voigt model. It is
      shown that only the viscous damping term in the original equation needs to be
      modified to account for the effect of elasticity. With experiment determined
      viscoelastic properties, the effects of elasticity on bubble oscillations are
      studied. Specifically, the inertial cavitation thresholds are determined using
      R(max)/R(0), and subharmonic signals from the emission of an oscillating bubble
      are estimated. The results show that the presence of the elasticity increases the
      threshold pressure for a bubble to oscillate inertially, and subharmonic signals
      may only be detectable in certain ranges of radius and pressure amplitude. These
      results should be easy to verify experimentally, and they may also be useful in
      cavitation detection and bubble-enhanced imaging.

PMID- 16419808
TI  - Noise levels in Johns Hopkins Hospital.
AB  - This article presents the results of a noise survey at Johns Hopkins Hospital in
      Baltimore, MD. Results include equivalent sound pressure levels (L(eq)) as a
      function of location, frequency, and time of day. At all locations and all times
      of day, the L(eq) indicate that a serious problem exists. No location is in
      compliance with current World Health Organization Guidelines, and a review of
      objective data indicates that this is true of hospitals throughout the world.
      Average equivalent sound levels are in the 50-60 dB(A) range for 1 min, 1/2, and
      24 h averaging time periods. The spectra are generally flat over the 63-2000 Hz
      octave bands, with higher sound levels at lower frequencies, and a gradual roll
      off above 2000 Hz. Many units exhibit little if any reduction of sound levels in
      the nighttime. Data gathered at various hospitals over the last 45 years indicate
      a trend of increasing noise levels during daytime and nighttime hours. The
      implications of these results are significant for patients, visitors, and
      hospital staff.

PMID- 16419818
TI  - Effect of voltage-dependent membrane properties on active force generation in
      cochlear outer hair cell.
AB  - A computational model is proposed to analyze the active force production in an
      individual outer hair cell (OHC) under high-frequency conditions. The model takes
      into account important biophysical properties of the cell as well as constraints
      imposed by the surrounding environment. The biophysical properties include the
      elastic, piezoelectric, and viscous characteristics of the cell wall. The effect
      of the environment is associated with the stiffness of the constraint and the
      drag forces acting on the cell due to the interaction with the external and
      internal viscous fluids. The study concentrated on a combined effect of the
      transmembrane potential, frequency, and stiffness of the constraints. The effect
      of the voltage-dependent stiffness of the cell was particularly investigated and
      it was found to be twofold. First, it results in higher sensitivity and
      nonlinearity of the OHC active force production in the physiological range.
      Second, it determines smaller active forces in the hyperpolarization range. The
      resonant properties of the active force as functions of voltage and the
      constraint stiffness were also analyzed. The obtained results can be important
      for a better understanding of the OHC active force production and the
      contribution of cell electromotility to the cochlear amplification, sensitivity,
      and nonlinearity.

PMID- 16419819
TI  - Evidence for a bipolar change in distortion product otoacoustic emissions during
      contralateral acoustic stimulation in humans.
AB  - The aim of this study was to investigate the activity of the medial olivocochlear
      (MOC) efferents during contralateral (CAS) and ipsilateral acoustic stimulation
      (IAS) by recording distortion product otoacoustic emission (DPOAE) suppression
      and DPOAE adaptation in humans. The main question was: do large bipolar changes
      in DPOAE level (transition from enhancement to suppression) also occur in humans
      when changing the primary tone level within a small range as described by Maison
      and Liberman for guinea pigs [J. Neurosci. 20, 4701-4707 (2000)]? In the present
      study, large bipolar changes in DPOAE level (14 dB on average across subjects)
      were found during CAS predominantly at frequencies where dips in the DPOAE fine
      structure occurred. Thus, effects of the second DPOAE source might be responsible
      for the observed bipolar effect. In contrast, comparable effects were not found
      during IAS as was reported in guinea pigs. Reproducibility of CAS DPOAEs was
      better than that for IAS DPOAEs. Thus, contralateral DPOAE suppression is
      suggested to be superior to ipsilateral DPOAE adaptation with regard to measuring
      the MOC reflex strength and for evaluating the vulnerability of the cochlea to
      acoustic overexposure in a clinical context.

PMID- 16419820
TI  - Perception of the envelope-beat frequency of inharmonic complex temporal
      envelopes.
AB  - Listeners can hear slow sinusoidal variations in the depth of sinusoidally
      amplitude-modulated (SAM) stimuli. Here, the SAM stimulus of frequency f(m) acts
      as the carrier, and the slow variation in depth of frequency f'm (referred to as
      "second-order" amplitude modulation) corresponds to a beat in the temporal
      envelope. Recent studies have suggested that second-order amplitude modulation
      perception is based on a modulation-distortion component or the "venelope" (the
      Hilbert envelope of the ac-coupled Hilbert envelope), both occurring at the
      envelope-beat frequency f'm. This was tested by transposing to the modulation
      domain the matching paradigm used by Schouten et al. [J. Acoust. Soc. Am. 34,
      1418-1424 (1962)]. Listeners estimated the envelope-beat frequency evoked by a 5
      Hz, second-order SAM white noise with f(m) either an integer multiple of f'm or
      shifted in frequency to make the complex envelope inharmonic. The results
      indicate that the perception of the envelope-beat frequency was affected by these
      shifts when f(m) < or = 20 Hz. This suggests that, at least at low modulation
      frequencies, the perceived envelope beat is not determined by a modulation
      distortion or venelope component, but rather relies on the time intervals between
      the main peaks of the first-order envelope.

PMID- 16419821
TI  - Spatial unmasking of birdsong in human listeners: energetic and informational
      factors.
AB  - Spatial unmasking describes the improvement in the detection or identification of
      a target sound afforded by separating it spatially from simultaneous masking
      sounds. This effect has been studied extensively for speech intelligibility in
      the presence of interfering sounds. In the current study, listeners identified
      zebra finch song, which shares many acoustic properties with speech but lacks
      semantic and linguistic content. Three maskers with the same long-term spectral
      content but different short-term statistics were used: (1) chorus (combinations
      of unfamiliar zebra finch songs), (2) song-shaped noise (broadband noise with the
      average spectrum of chorus), and (3) chorus-modulated noise (song-shaped noise
      multiplied by the broadband envelope from a chorus masker). The amount of masking
      and spatial unmasking depended on the masker and there was evidence of release
      from both energetic and informational masking. Spatial unmasking was greatest for
      the statistically similar chorus masker. For the two noise maskers, there was
      less spatial unmasking and it was wholly accounted for by the relative target and
      masker levels at the acoustically better ear. The results share many features
      with analogous results using speech targets, suggesting that spatial separation
      aids in the segregation of complex natural sounds through mechanisms that are not
      specific to speech.

PMID- 16419822
TI  - Detection of spectrally complex signals in comodulated maskers: effect of
      temporal fringe.
AB  - This study tested the hypothesis that masking release for a complex signal under
      conditions where signal energy is present in all frequency regions occupied by
      the masker is attributable to an across-frequency-channel comodulation masking
      release (CMR) process. The approach was to identify a signature CMR trait, and to
      then determine if that trait was associated with the detection advantage for
      complex signals. The selected trait was the decline of CMR in the presence of a
      random temporal fringe. In experiment 1, a masking release was observed for a
      four-component harmonic signal presented in a comodulated masker, and this
      masking release was diminished by the random temporal fringe. A similar effect
      was observed in experiment 2 for a four-component inharmonic signal. These
      results support the hypothesis that a CMR can be measured for a complex signal
      even when there is substantial spectral overlap between the signal and its
      comodulated masker. This finding has consequences for CMR models since it
      demonstrates that the presence of "signal-free" cue bands is not a prerequisite
      for CMR, and that the presence of comodulation during the signal window is not
      sufficient to result in CMR.

PMID- 16419823
TI  - Reduced contribution of a nonsimultaneous mistuned harmonic to residue pitch.
AB  - Ciocca and Darwin [V. Ciocca and C. J. Darwin, J. Acoust. Soc. Am. 105, 2421-2430
      (1999)] reported that the shift in residue pitch caused by mistuning a single
      harmonic (the fourth out of the first 12) was the same when the mistuned harmonic
      was presented after the remainder of the complex as when it was simultaneous,
      even though subjects were asked to ignore the pure-tone percept. The present
      study tried to replicate this result, and investigated the role of the presence
      of the nominally mistuned harmonic in the matching sound. Subjects adjusted a
      "matching" sound so that its pitch equaled that of a subsequent 90-ms complex
      tone (12 harmonics of a 155-Hz F0), whose mistuned (+/-3%) third harmonic was
      presented either simultaneously with or after the remaining harmonics. In
      experiment 1, the matching sound was a harmonic complex whose third harmonic was
      either present or absent. In experiments 2A and 2B, the target and matching sound
      had nonoverlapping spectra. Pitch shifts were reduced both when the mistuned
      component was nonsimultaneous, and when the third harmonic was absent in the
      matching sound. The results indicate a shorter than originally estimated time
      window for obligatory integration of nonsimultaneous components into a virtual
      pitch.

PMID- 16419824
TI  - A perceptual learning investigation of the pitch elicited by amplitude-modulated
      noise.
AB  - Noise that is amplitude modulated at rates ranging from 40 to 850 Hz can elicit a
      sensation of pitch. Here, the processing of this temporally based pitch was
      investigated using a perceptual-learning paradigm. Nine listeners were trained (1
      hour per day for 6-8 days) to discriminate a standard rate of sinusoidal
      amplitude modulation (SAM) from a faster rate in a single condition (150 Hz SAM
      rate, 5 kHz low-pass carrier). All trained listeners improved significantly on
      that condition. These trained listeners subsequently showed no more improvement
      than nine untrained controls on pure-tone and rippled-noise discrimination with
      the same pitch, and on SAM-rate discrimination with a 30 Hz rate, although they
      did show some improvement with a 300 Hz rate. In addition, most trained, but not
      control, listeners were worse at detecting SAM at 150 Hz after, compared to
      before training. These results indicate that listeners can learn to improve their
      ability to discriminate SAM rate with multiple-hour training and that the
      mechanism that is modified by learning encodes (1) the pitch of SAM noise but not
      that of pure tones and rippled noise, (2) different SAM rates separately, and (3)
      differences in SAM rate more effectively than cues for SAM detection.

PMID- 16419825
TI  - The advantage of knowing where to listen.
AB  - This study examined the role of focused attention along the spatial (azimuthal)
      dimension in a highly uncertain multitalker listening situation. The task of the
      listener was to identify key words from a target talker in the presence of two
      other talkers simultaneously uttering similar sentences. When the listener had no
      a priori knowledge about target location, or which of the three sentences was the
      target sentence, performance was relatively poor-near the value expected simply
      from choosing to focus attention on only one of the three locations. When the
      target sentence was cued before the trial, but location was uncertain,
      performance improved significantly relative to the uncued case. When spatial
      location information was provided before the trial, performance improved
      significantly for both cued and uncued conditions. If the location of the target
      was certain, proportion correct identification performance was higher than 0.9
      independent of whether the target was cued beforehand. In contrast to studies in
      which known versus unknown spatial locations were compared for relatively simple
      stimuli and tasks, the results of the current experiments suggest that the focus
      of attention along the spatial dimension can play a very significant role in
      solving the "cocktail party" problem.

PMID- 16419826
TI  - Discrimination of speaker size from syllable phrases.
AB  - The length of the vocal tract is correlated with speaker size and, so, speech
      sounds have information about the size of the speaker in a form that is
      interpretable by the listener. A wide range of different vocal tract lengths
      exist in the population and humans are able to distinguish speaker size from the
      speech. Smith et al. [J. Acoust. Soc. Am. 117, 305-318 (2005)] presented vowel
      sounds to listeners and showed that the ability to discriminate speaker size
      extends beyond the normal range of speaker sizes which suggests that information
      about the size and shape of the vocal tract is segregated automatically at an
      early stage in the processing. This paper reports an extension of the size
      discrimination research using a much larger set of speech sounds, namely, 180
      consonant-vowel and vowel-consonant syllables. Despite the pronounced increase in
      stimulus variability, there was actually an improvement in discrimination
      performance over that supported by vowel sounds alone. Performance with vowel
      consonant syllables was slightly better than with consonant-vowel syllables.
      These results support the hypothesis that information about the length of the
      vocal tract is segregated at an early stage in auditory processing.

PMID- 16419828
TI  - Synergistic modes of vocal tract articulation for American English vowels.
AB  - The purpose of this study was to investigate the spatial similarity of vocal
      tract shaping patterns across speakers and the similarity of their acoustic
      effects. Vocal tract area functions for 11 American English vowels were obtained
      from six speakers, three female and three male, using magnetic resonance imaging
      (MRI). Each speaker's set of area functions was then decomposed into mean area
      vectors and representative modes (eigenvectors) using principal components
      analysis (PCA). Three modes accounted for more than 90% of the variance in the
      original data sets for each speaker. The general shapes of the first two modes
      were found to be highly correlated across all six speakers. To demonstrate the
      acoustic effects of each mode, both in isolation and combined, a mapping between
      the mode scaling coefficients and [F1, F2] pairs was generated for each speaker.
      The mappings were unique for all six speakers in terms of the exact shape of the
      [F1, F2] vowel space, but the general effect of the modes was the same in each
      case. The results support the idea that the modes provide a common system for
      perturbing a unique underlying neutral vocal tract shape.

PMID- 16419829
TI  - Interacting effects of syllable and phrase position on consonant articulation.
AB  - The complexities of how prosodic structure, both at the phrasal and syllable
      levels, shapes speech production have begun to be illuminated through studies of
      articulatory behavior. The present study contributes to an understanding of
      prosodic signatures on articulation by examining the joint effects of phrasal and
      syllable position on the production of consonants. Articulatory kinematic data
      were collected for five subjects using electromagnetic articulography (EMA) to
      record target consonants (labial, labiodental, and tongue tip), located in (1)
      either syllable final or initial position and (2) either at a phrase edge or
      phrase medially. Spatial and temporal characteristics of the consonantal
      constriction formation and release were determined based on kinematic landmarks
      in the articulator velocity profiles. The results indicate that syllable and
      phrasal position consistently affect the movement duration; however, effects on
      displacement were more variable. For most subjects, the boundary-adjacent
      portions of the movement (constriction release for a preboundary coda and
      constriction formation for a postboundary onset) are not differentially affected
      in terms of phrasal lengthening-both lengthen comparably.

PMID- 16419827
TI  - Psychophysical estimates of nonlinear cochlear processing in younger and older
      listeners.
AB  - The primary goal of this project was to compare the performance of younger and
      older listeners on a number of psychophysical measures thought to be influenced
      by nonlinear cochlear processing. Younger (mean of 25.6 years) and older (mean of
      63.8 years) listeners with normal hearing were matched (within 5 dB) according to
      their quiet thresholds at the two test frequencies of 1200 and 2400 Hz. They were
      similarly matched at the adjacent octave frequencies of 600 and 4800 Hz (within 5
      dB at one and 9 dB at the other). Performance was compared on measures of
      auditory filter shape, psychophysical suppression, and growth of forward masking.
      There was no difference between the two age groups on these psychophysical
      estimates reflecting nonlinear processing, suggesting that aging per se does not
      affect the cochlear nonlinearity, at least for the ages sampled here. The results
      did, however, consistently demonstrate an age-related increase in the
      susceptibility to forward masking.

PMID- 16419831
TI  - Interference from audio distracters during speechreading.
AB  - Although many audio-visual speech experiments have focused on situations where
      the presence of an incongruent visual speech signal influences the perceived
      utterance heard by an observer, there are also documented examples of a related
      effect in which the presence of an incongruent audio speech signal influences the
      perceived utterance seen by an observer. This study examined the effects that
      different distracting audio signals had on performance in a color and number
      keyword speechreading task. When the distracting sound was noise, time-reversed
      speech, or continuous speech, it had no effect on speechreading. However, when
      the distracting audio signal consisted of speech that started at the same time as
      the visual stimulus, speechreading performance was substantially degraded. This
      degradation did not depend on the semantic similarity between the target and
      masker speech, but it was substantially reduced when the onset of the audio
      speech was shifted relative to that of the visual stimulus. Overall, these
      results suggest that visual speech perception is impaired by the presence of a
      simultaneous mismatched audio speech signal, but that other types of audio
      distracters have little effect on speechreading performance.

PMID- 16419830
TI  - The influence of noise on vowel and consonant cues.
AB  - This study assessed the acoustic and perceptual effect of noise on vowel and stop
      consonant spectra. Multi-talker babble and speech-shaped noise were added to
      vowel and stop stimuli at -5 to +10 dB S/N, and the effect of noise was
      quantified in terms of (a) spectral envelope differences between the noisy and
      clean spectra in three frequency bands, (b) presence of reliable F1 and F2
      information in noise, and (c) changes in burst frequency and slope. Acoustic
      analysis indicated that F1 was detected more reliably than F2 and the largest
      spectral envelope differences between the noisy and clean vowel spectra occurred
      in the mid-frequency band. This finding suggests that in extremely noisy
      conditions listeners must be relying on relatively accurate F1 frequency
      information along with partial F2 information to identify vowels. Stop consonant
      recognition remained high even at -5 dB despite the disruption of burst cues due
      to additive noise, suggesting that listeners must be relying on other cues,
      perhaps formant transitions, to identify stops.

PMID- 16419832
TI  - Self-to-other ratios measured in an opera chorus in performance.
AB  - Four volunteer members of the chorus of Opera Australia, representing four
      different voice categories, wore binaural pairs of wireless microphones during a
      penultimate dress rehearsal on the Opera Theater stage of the Sydney Opera House.
      From the recordings, data were obtained on sound levels and on the self-to-other
      ratios (SORs). The sound levels were comparable to those found in loud music in
      chamber choir performance. The average SOR ranged from +10 to +15 dB. Compared to
      chamber choirs in other types of room, the SOR values were high. On a separate
      occasion, the stage support parameters ST1 (early reflections) and ST2 (late
      reflections) were measured over the whole stage area. ST1 was about -16 dB, which
      is typical for opera stages, and -20 dB for ST2, which is unusually low. It is
      concluded that the SOR in the opera chorus depends mostly on choir formation,
      which is highly variable, and that an opera chorus artist generally can hear his
      or her own voice very well, but little of the others and of the orchestra. This
      was confirmed by informal listening to the recordings.

PMID- 16419833
TI  - Kramers-Kronig analysis of attenuation and dispersion in trabecular bone.
AB  - A restricted-bandwidth form of the Kramers-Kronig dispersion relations is applied
      to in vitro measurements of ultrasonic attenuation and dispersion properties of
      trabecular bone specimens from bovine tibia. The Kramers-Kronig analysis utilizes
      only experimentally measured properties and avoids extrapolation of ultrasonic
      properties beyond the known bandwidth. Compensation for the portions of the
      Kramers-Kronig integrals over the unknown bandwidth is partially achieved by the
      method of subtractions, where a subtraction frequency acts as an adjustable
      parameter. Good agreement is found between experimentally measured and Kramers
      Kronig reconstructed dispersions. The restricted-bandwidth approach improves upon
      other forms of the Kramers-Kronig relations and may provide further insight into
      how ultrasound interacts with trabecular bone.

PMID- 16419834
TI  - Localization of aerial pure tones by pinnipeds.
AB  - In this study, minimum audible angles (MAAs) of aerial pure tones were measured
      in and compared between a northern elephant seal (Mirounga angustirostris), a
      harbor seal (Phoca vitulina), and a California sea lion (Zalophus californianus).
      Testing was conducted between 0.8 and 16 kHz in the elephant seal and 0.8 and 20
      kHz in the harbor seal and sea lion in a hemi-anechoic chamber using a left/right
      psychophysical procedure. Performance for the same frequencies was also
      quantified for discrete speaker separation of 5 degrees from the mid-line. For
      all subjects, MAAs ranged from approximately 3 degrees to 15 degrees and were
      generally equal to or larger than those previously measured in the same subjects
      with a broadband signal. Performance at 5 degrees ranged from chance to 97%
      correct, depending on frequency and subject. Poorest performance in the sea lion
      and harbor seal occurred at intermediate frequencies, which is consistent with
      the duplex theory of sound localization. In contrast, the elephant seal's poorest
      performance occurred at higher frequencies. The elephant seal's result suggests
      an inferior ability to utilize interaural level differences and is perhaps
      related to best hearing sensitivity shifted toward lower frequencies in this
      species relative to other pinnipeds.

PMID- 16419835
TI  - Doppler-shift compensation in the Taiwanese leaf-nosed bat (Hipposideros
      terasensis) recorded with a telemetry microphone system during flight.
AB  - Biosonar behavior was examined in Taiwanese leaf-nosed bats (Hipposideros
      terasensis; CF-FM bats) during flight. Echolocation sounds were recorded using a
      telemetry microphone mounted on the bat's head. Flight speed and three
      dimensional trajectory of the bat were reconstructed from images taken with a
      dual high-speed video camera system. Bats were observed to change the intensity
      and emission rate of pulses depending on the distance from the landing site.
      Frequencies of the dominant second harmonic constant frequency component (CF2) of
      calls estimated from the bats' flight speed agreed strongly with observed values.
      Taiwanese leaf-nosed bats changed CF2 frequencies depending on flight speed,
      which caused the CF2 frequencies of the Doppler-shifted echoes to remain
      constant. Pulse frequencies were also estimated using echoes returning directly
      ahead of the bat and from its sides for two different flight conditions: landing
      and U-turn. Bats in flight may periodically alter their attended angles from the
      front to the side when emitting echolocation pulses.

PMID- 16419836
TI  - Origin of the double- and multi-pulse structure of echolocation signals in
      Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientialis).
AB  - The signals of dolphins and porpoises often exhibit a multi-pulse structure.
      Here, echolocation signal recordings were made from four geometrically distinct
      positions of seven Yangtze finless porpoises temporarily housed in a relatively
      small, enclosed area. Some clicks demonstrated double-pulse, and others multi
      pulse, structure. The interpulse intervals between the first and second pulse of
      the double- and multi-pulse clicks were significantly different among data from
      the four different positions (p < 0.01, one-way ANOVA). These results indicate
      that the interpulse interval and structure of the double- and multi-pulse
      echolocation signals depend on the hydrophone geometry of the animal, and that
      the double- and multi-pulse structure of echolocation signals in Yangtze finless
      porpoise is not caused by the phonating porpoise itself, but by the multipath
      propagation of the signal. Time delays in the 180 degrees phase-shifted surface
      reflection pulse and the nonphase-shifted bottom reflection pulse of the multi
      pulse structures, relative to the direct signal, can be used to calculate the
      distance to a phonating animal.

PMID- 16419838
TI  - Nonlinear resonant ultrasound spectroscopy (NRUS) applied to damage assessment in
      bone.
AB  - Nonlinear resonant ultrasound spectroscopy (NRUS) is a resonance-based technique
      exploiting the significant nonlinear behavior of damaged materials. In NRUS, the
      resonant frequency(ies) of an object is studied as a function of the excitation
      level. As the excitation level increases, the elastic nonlinearity is manifest by
      a shift in the resonance frequency. This study shows the feasibility of this
      technique for application to damage assessment in bone. Two samples of bovine
      cortical bone were subjected to progressive damage induced by application of
      mechanical cycling. Before cycling commenced, and at each step in the cycling
      process, NRUS was applied for damage assessment. For independent assessment of
      damage, high-energy x-ray computed tomography imaging was performed but was only
      useful in identifying the prominent cracks. As the integral quantity of damage
      increased, NRUS revealed a corresponding increase in the nonlinear response. The
      measured change in nonlinear response is much more sensitive than the change in
      linear modulus. The results suggest that NRUS could be a potential tool for micro
      damage assessment in bone. Further work must be carried out for a better
      understanding of the physical nature of damaged bone and for the ultimate goal of
      the challenging in vivo implementation of the technique.

PMID- 16419837
TI  - Sei whale sounds recorded in the Antarctic.
AB  - Sei whales are the least well known acoustically of all the rorquals, with only
      two brief descriptions of their calls previously reported. Recordings of low
      frequency tonal and frequency swept calls were made near a group of four or five
      sei whales in waters west of the Antarctic Peninsula on 19 February 2003. These
      whales also produced broadband sounds which can be described as growls or
      whooshes. Many of the tonal and frequency swept calls (30 out of 68) consist of
      multiple parts with a frequency step between the two parts, this being the most
      unique characteristic of the calls, allowing them to be distinguished from the
      calls of other whale species. The average duration of the tonal calls is 0.45 +/-
      0.3 s and the average frequency is 433 +/- 192 Hz. Using a calibrated seafloor
      recorder to determine the absolute calibration of a sonobuoy system, the maximum
      source level of the tonal calls was 156 +/- 3.6 dB re 1 microPa at 1 m. Each call
      had different character and there was no temporal pattern in the calling.

PMID- 16419839
TI  - Superresolution ultrasound imaging using back-projected reconstruction.
AB  - An ultrasound technique for imaging objects significantly smaller than the source
      wavelength is investigated. Signals from a focused beam are recorded over an
      image plane in the acoustic farfield and backprojected in the wave-vector domain
      to the focal plane. A superresolution image recovery method is then used to
      analyze the Fourier spatial frequency spectrum of the signal in an attempt to
      deduce the location and size of objects in this plane. The physical foundation
      for the method is rooted in the fact that high spatial frequencies introduced by
      the object in fact affect the lower (nonevanescent) spatial frequencies of the
      overall signal. The technique achieves this by using a priori measurements of the
      ultrasound focus in water, which gives full spectral information about the image
      source. A guess is then made regarding the size and location of the object that
      distorted the field, and this is convolved with the a priori measurement, thus
      creating a candidate image. A large number of candidates are generated and the
      one whose spectrum best matches the uncorrected image is accepted. The method is
      demonstrated using 0.34- and 0.60-mm wires with a focused 1.05-MHz ultrasound
      signal and then a human hair (approximately 0.03 mm) with a 4.7-MHz signal.

PMID- 16419846
TI  - [Screening and nutritional management of hospitalized diabetic malnourished
      patients in a podiatry unit].

PMID- 16419847
TI  - [Cancerous wounds].

PMID- 16419848
TI  - [Difficulties in the medical examination during police custody].

PMID- 16419849
TI  - [Evolution of the psychiatric sector in the penitentiary milieu].

PMID- 16419850
TI  - [The first French hospital unit for prisoners].

PMID- 16419851
TI  - [Opening of the interregional secure hospital unit in Nancy..., the nurses' point
      of view].

PMID- 16419852
TI  - [Medical-psychological regional services care at the Nice prison].

PMID- 16419853
TI  - [Programs in place to prevent suicide among prisoners].

PMID- 16419855
TI  - [IA psychiatric consultation for sexual aggression perpetrators].

PMID- 16419854
TI  - [Specific management of women in prison].

PMID- 16419856
TI  - [Bibliography. Care for prisoners].

PMID- 16419857
TI  - [To be a prison nurse, the acquirement of training and experience suffices].

PMID- 16419858
TI  - [4/4 Preventing professional burnout].

PMID- 16419859
TI  - Asymptotic analysis of collision-induced timing shifts in return-to-zero quasi
      linear systems with predispersion and postdispersion compensation.
AB  - An asymptotic method for calculating the collision-induced frequency and timing
      shifts for quasi-linear pulses in return-to-zero, wavelength-division multiplexed
      systems with predispersion and postdispersion compensation is developed.
      Predictions of the asymptotic theory agree well with quadrature and direct
      numerical simulations. Using this theory, computational savings of many orders of
      magnitude can be realized over direct numerical simulations.

PMID- 16419860
TI  - Filter of optical vortices: highly twisted high-birefringence optical fibers.
AB  - Modes and bandgap structure of highly twisted high-birefringence weakly guiding
      fibers are studied in the scalar approximation. It is shown that within the gap
      the system can serve as a filter of circular optical vortices.

PMID- 16419861
TI  - Increased solubility of molecular hydrogen in UV-exposed germanosilicate fibers.
AB  - Spectral properties of photoinduced fiber Bragg gratings written in
      germanosilicate fibers and subjected to hydrogen loading at a pressure of 150-170
      MPa have been studied. It was observed, for the first time to our knowledge, that
      hydrogen dissolution in the glass network at such high pressures leads not only
      to a Bragg wavelength shift but also to a considerable alteration of the grating
      reflectivity. The relative magnitude of the latter effect is independent of the
      dissolved hydrogen concentration and is defined mainly by the core glass
      properties and the UV-irradiation conditions. The alteration of the grating
      reflectivity observed experimentally is explained by increased solubility of
      molecular hydrogen in UV-exposed germanosilicate glass.

PMID- 16419862
TI  - Direct measurement of frequency and polarization dependences of cross-phase
      modulation in fibers from high-resolution optical spectra.
AB  - We present the results of an experiment for frequency and polarization dependence
      characterization of non-linear cross-phase-modulation (XPM) effects in optical
      fibers. The measurement technique is based on the direct analysis of high
      resolution optical spectra of a signal wave that is phase modulated by an
      intensity-modulated pump wave. Measurement results provide experimental
      confirmation of the scalar character, over the whole resonant frequency range, of
      the electrostrictive contribution to the nonlinear refractive index. Also, the
      results confirm experimentally the relation describing the polarization
      dependence of the Kerr contribution to XPM in non-polarization-maintaining
      fibers.

PMID- 16419863
TI  - High-power single-polarization and single-transverse-mode fiber laser with an all
      fiber cavity and fiber-grating stabilized spectrum.
AB  - Conventionally, large-mode-area (LMA) fiber lasers use free-space polarizing
      components to achieve linear polarization output. External components, however,
      significantly limit laser robustness and power scalability. We demonstrate, to
      the best of our knowledge, the first high-power all-fiber cavity single
      polarization single-transverse-mode LMA fiber laser, without the use of free
      space polarizing components. This has been achieved by using tightly coiled high
      birefringence 20 microm core LMA fiber. The lasing spectrum at 1085 nm has been
      stabilized by a fiber grating, spliced at one end of a LMA fiber. Up to 405 W of
      single-polarization output with a polarization extinction of >19 dB with a narrow
      spectrum (1.9 nm FWHM) and in a single-transverse mode (M2 < 1.1) has been
      demonstrated. The simplicity of a monolithic-cavity approach is highly beneficial
      for a number of applications, including the use of a fiber laser for nonlinear
      wavelength conversion and for coherent and spectral beam combining.

PMID- 16419864
TI  - Correlation dimension signature of wideband chaos synchronization of
      semiconductor lasers.
AB  - Chaos data analysis has been performed on the chaotic output power time series
      data from a synchronized transmitter-receiver pair of semiconductor lasers. The
      system uses an asymmetric, bidirectional coupling configuration between the
      master (transmitter), which is a laser diode with optical feedback, and a stand
      alone slave semiconductor laser. The correlation dimension of the chaotic time
      series has a minimum value of 4, which was obtained from high-bandwidth
      measurements. The correlation dimensions for both the master and the synchronized
      slave are identical when the cross-correlation coefficient of the synchronized
      chaos is above 0.9. These results establish correlation dimension analysis as an
      effective tool for the determination of the quality of wideband chaos
      synchronization.

PMID- 16419865
TI  - Simultaneous demodulation technique for a multiplexed fiber Fizeau interferometer
      and fiber Bragg grating sensor system.
AB  - We propose a demodulation technique for a multiplexed fiber Fizeau interferometer
      (FFI) and fiber Bragg grating (FBG) sensor system using the discrete wavelet
      transform with signal processing enhancements. This simple and flexible
      demodulation technique determines the cavity length of FFI and the Bragg
      wavelength of FBG simultaneously and is especially suited for quasi-static
      measurements. We demonstrate this demodulation technique by performing some
      strain measurements, and a strain resolution of 1.0 microepsilon and an accuracy
      of 2.6 microepsilon are obtained. The maximum cross-talk of the sensor system is
      6% of the applied strains.

PMID- 16419866
TI  - Theoretical realization of holey fiber with flat chromatic dispersion and large
      mode area: an intriguing defected approach.
AB  - We present a novel design approach for realizing holey fibers (HFs) with flat
      dispersion characteristics and large mode area based on the existence of an
      artificially defected air-hole ring in the cladding, and on the inclusion of
      additional defected air holes in the core of the fiber. This unique type of HF
      can be used for achieving remarkable flat dispersion characteristics as well as a
      large mode area, which are particularly useful for high-speed data transmission.
      The validation of the proposed design is done by adopting an efficient full
      vectorial finite element method for optical characterization of HFs. The proposed
      fiber can be employed in reconfigurable optical transmission systems for
      performing wavelength division multiplexing operation. Typical characteristics of
      the proposed HF are a flattened dispersion of 6.3 +/- 0.5 ps/km/nm from 1.45 to
      1.65 microm and an effective mode area as large as 100 microm2 in the same
      frequency range.

PMID- 16419867
TI  - Intrachannel four-wave mixing in highly dispersed return-to-zero differential
      phase-shift-keyed transmission with a nonsymmetric dispersion map.
AB  - Nonlinear penalties due to intrachannel four-wave mixing (IFWM) in highly
      dispersed return-to-zero differential-phase-shift-keyed transmission are studied
      for both symmetric and nonsymmetric dispersion maps. As the dispersion map
      changes from symmetric to nonsymmetric, the nonlinear amplitude fluctuation
      overtakes the effect of the nonlinear phase fluctuation and dominates the
      system's nonlinear performance. The effect of IFWM on the bit error rate is
      assessed by using the semianalytical method.

PMID- 16419868
TI  - Speckle photography: mixed domain fractional Fourier motion detection.
AB  - A reflection-based optical implementation of two simultaneous scale-invariant
      fractional Fourier transforms (FRTs) is used to develop a novel compact speckle
      photographic system. The system allows the independent determination of both
      surface tilting and in-plane translational motion from two sequential mixed
      domain images captured using a single camera.

PMID- 16419869
TI  - Efficient computation of quadratic-phase integrals in optics.
AB  - We present a fast NlogN time algorithm for computing quadratic-phase integrals.
      This three-parameter class of integrals models propagation in free space in the
      Fresnel approximation, passage through thin lenses, and propagation in quadratic
      graded-index media as well as any combination of any number of these and is
      therefore of importance in optics. By carefully managing the sampling rate, one
      need not choose N much larger than the space-bandwidth product of the signals,
      despite the highly oscillatory integral kernel. The only deviation from exactness
      arises from the approximation of a continuous Fourier transform with the discrete
      Fourier transform. Thus the algorithm computes quadratic-phase integrals with a
      performance similar to that of the fast-Fourier-transform algorithm in computing
      the Fourier transform, in terms of both speed and accuracy.

PMID- 16419870
TI  - Generation of an elliptic Bessel beam.
AB  - In an elliptic coordinate system the solution for a diffraction-free beam is
      given by a Mathieu beam, which is mathematically complicated and therefore takes
      considerable computational time and a large memory space. A technique is reported
      for the generation of elliptic hollow beams, which are actually scaled versions
      of higher-order Bessel beams. The analysis is based on the fact that stretching
      coordinates in the space domain results in a contraction of the coordinates in
      the frequency domain, along with a change in the overall amplitude of the
      spectrum. The beam, produced holographically, is structurally stable and retains
      its shape up to approximately 1 m.

PMID- 16419871
TI  - Single-camera panoramic stereo system with single-viewpoint optics.
AB  - A simple and successful design for a panoramic stereo system that uses a single
      camera and multiple mirrors is presented. A wide-baseline stereo enhances the
      three-dimensional reconstruction accuracy even with a single camera. The
      feasibility of the system as a practical stereo sensor has been demonstrated with
      experiments in an indoor environment.

PMID- 16419872
TI  - Probe beam size effect on the measurement of the distance between the probe beam
      and the sample in photothermal deflection.
AB  - A distance-scan method to determine the distance between the probe beam and
      sample, which is not easily measured exactly, in photothermal deflection (PD) was
      reported, with which the distance and thermal diffusivity of the deflecting
      medium can be simultaneously measured. Probe beam size effect (PBSE) on PD phase
      signal was quantitatively analyzed to clearly show its physical meaning. The
      measured distance was experimentally verified as correct and reliable, and the
      measured thermal diffusivities of N2 and CO2 are in good agreement with the
      literature values. They could not be precisely measured by phase signal without
      considering the PBSE.

PMID- 16419873
TI  - Field concentration by exciting surface defect modes.
AB  - We propose a design for patterned metal-coated surfaces allowing efficient
      broadband coupling of radiation to a fully localized surface cavity mode,
      resulting in a zero-focal-length concentrator. This finite structure exploits the
      interplay of a defect mode cavity with a coupling grating and is investigated
      through the modal expansion method and finite-difference time domain
      calculations.

PMID- 16419874
TI  - Coupling into the slow light mode in slab-type photonic crystal waveguides.
AB  - Coupling external light signals into a photonic crystal (PhC) waveguide becomes
      increasingly inefficient as the group velocity of the waveguiding mode slows
      down. We have systematically studied the efficiency of coupling in the slow light
      regime for samples with different truncations of the photonic lattice at the
      coupling interface between a strip waveguide and a PhC waveguide. An inverse
      power law dependence is found to best fit the experimental scaling of the
      coupling loss on the group index. Coupling efficiency is significantly improved
      up to group indices of 100 for a truncation of the lattice that favors the
      appearance of photonic surface states at the coupling interface in resonance with
      the slow light mode.

PMID- 16419875
TI  - Yb-doped KY(WO4)2 planar waveguide laser.
AB  - High-quality monoclinic KY(WO4)2 optical waveguides were grown by liquid-phase
      epitaxy, and laser operation of an Yb-doped KY(WO4)2 waveguide was demonstrated
      for the first time to our knowledge. Continuous-wave laser emission near 1 microm
      was achieved with both surface and buried planar waveguides. An output power of
      290 mW was obtained in the fundamental mode and the slope efficiency was above
      80%.

PMID- 16419876
TI  - Polarization-independent optical directional coupler based on slot waveguides.
AB  - A polarization-independent optical directional coupler based on slot waveguides
      is proposed and analyzed by using rigorous full-vectorial analysis methods based
      on a finite-element scheme. Properly choosing materials and structural parameters
      makes the coupling length for quasi-TE modes become equal to that for quasi-TM
      modes. Tolerances to operating wavelength and structural parameters are also
      discussed. The proposed coupler can be used for highly integrated optical
      circuits without polarization diversity schemes.

PMID- 16419877
TI  - Nanofluidic tuning of photonic crystal circuits.
AB  - By integrating soft-lithography-based nanofluidics with silicon nanophotonics, we
      demonstrate dynamic, liquid-based addressing and high deltan/n (approximately
      0.1) refractive index modulation of individual features within photonic
      structures at subwavelength length scales. We show ultracompact tunable spectral
      filtering through nanofluidic targeting of a single row of holes within a planar
      photonic crystal. We accomplished this with an optofluidic integration
      architecture comprising a nanophotonic layer, a nanofluidic delivery structure,
      and a microfluidic control engine. Variants of this technique could enable
      dynamic reconfiguration of photonic circuits, selective introduction of optical
      nonlinearities, or delivery of single molecules into resonant cavities for
      biodetection.

PMID- 16419878
TI  - Broad-bandwidth shot-noise-limited class-A operation of a monomode semiconductor
      fiber-based ring laser.
AB  - We demonstrate the operation of a monomode semiconductor laser with a relative
      intensity noise limited by the shot-noise floor, -156 dB/Hz for a typical
      detected photocurrent of 1 mA, over a large frequency range from 50 MHz to 18
      GHz. We achieve direct control of photon lifetime to turn an initially class-B
      laser into a relaxation-oscillation-free class-A one while preserving strict
      single-mode operation. Finally, we confirm experimentally that the laser
      operation in the desired class-A regime allows a dramatic filtering out of the
      relative intensity noise.

PMID- 16419879
TI  - Laser and self-Raman-laser oscillations of PBMoO4:Nd3+ crystal under laser diode
      pumping.
AB  - Different regimes of laser operation and stimulated Raman scattering (SRS) for a
      laser diode (LD)-pumped PbMoO4:Nd3+ crystal have been investigated. Under 1.5 W
      LD pumping, the output power of the PbMoO4:Nd3+ laser in the free-running mode at
      1056 nm reached 0.65 W with a slope efficiency of up to 53%. Using different LiF:
      F-2 saturable absorbers, we achieved a maximum pulse energy of 11 microJ at a 1.4
      ns pulse duration and a maximum output power of 0.35 W (10 microJ) at a 7 ns
      pulse width in the passively Q-switched mode. PbMoO4:Nd3+ self-Raman-laser
      operation at 1163 nm (first Stokes) was obtained for the first time, to our
      knowledge. The self-Raman-laser output pulse energy was measured to be as high as
      6 microJ and the pulse duration was estimated to be shorter than 500 ps.

PMID- 16419880
TI  - Damage and ablation of large bandgap dielectrics induced by a 46.9 nm laser beam.
AB  - We applied a 0.3 mJ, 1.7 ns, 46.9 nm soft-x-ray argon laser to ablate the surface
      of large bandgap dielectrics: CaF2 and LiF crystals. We studied the ablation
      versus the fluence of the soft-x-ray beam, varying the fluence in the range 0.05
      3 J/cm2. Ablation thresholds of 0.06 and 0.1 J/cm2 and ablation depths of 14 and
      20 nm were found for CaF2 and LiF, respectively. These results define new
      ablation conditions for these large bandgap dielectrics that can be of interest
      for the fine processing of these materials.

PMID- 16419881
TI  - Optical parametric generation of a mid-infrared continuum in orientation
      patterned GaAs.
AB  - We have generated an ultrabroad mid-infrared continuum by using single-pass
      optical parametric generation (OPG) in orientation-patterned GaAs (OP-GaAs). The
      spectrum spans more than an octave, from 4.5 to 10.7 microm, measured 20 dB down
      from the peak. The 17.5 mm long, 0.5 mm thick, all-epitaxially-grown OP-GaAs
      sample with a 166.6-microm quasi-phase-matching period was pumped with 3.1-3.3
      microm wavelength, 1 ps pulses up to 2 microJ in energy. The OPG threshold was
      observed at 55 nJ pump energy with the pump polarized along the [111] crystal
      direction. The slope efficiency near threshold was 51%, and the external
      conversion efficiency was as high as 15%.

PMID- 16419882
TI  - Optical breathers in semiconductor quantum dots.
AB  - A theory of resonant optical breathers in the presence of single and biexciton
      transitions in an ensemble of inhomogeneously broadened semiconductor quantum
      dots is constructed. Explicit analytical expressions for the breather shape and
      parameters for experimental investigations are proposed.

PMID- 16419883
TI  - Coupled spatial-soliton pairs in saturable nonlinear media.
AB  - We present a simple and straightforward approach to investigate coupled spatial
      soliton pairs of two copropagating mutually incoherent (i.e., both beams are
      fully spatially and temporally coherent, but are incoherent with respect to one
      another) light beams in saturable nonlinear media. The approach provides a deeper
      understanding of coupled spatial-soliton pairs and reveals many interesting
      features, including the entire existence curve of such solitons.

PMID- 16419884
TI  - Discrete damage traces from filamentation of Gauss-Bessel pulses.
AB  - Filamentation of Bessel-Gauss pulses propagating in borosilicate glass is found
      to produce damage lines extending over hundreds of micrometers and consisting of
      discrete, equidistant damage spots. These discrete damage traces are explained by
      self-regeneration of Gauss-Bessel beams during propagation and are potentially
      applicable in laser microfabrication of transparent materials.

PMID- 16419885
TI  - Optical-damage-free guided second-harmonic generation in 1% MgO-doped
      stoichiometric lithium tantalate.
AB  - Room-temperature cw second-harmonic generation from telecom wavelengths, with 30%
      W(-1) cm(-2) efficiency and second-harmonic power levels up to 41 mW, was
      achieved in buried waveguides fabricated by reverse-proton exchange in 1% MgO
      doped stoichiometric lithium tantalate without any evidence of optical damage.
      The technology proves suitable for the realization of efficient nonlinear
      frequency converters and all-optical devices.

PMID- 16419886
TI  - Laser filaments generated and transmitted in highly turbulent air.
AB  - The initiation and propagation of a filament generated by ultrashort laser pulses
      in turbulent air is investigated experimentally. A filament can be generated and
      propagated even after the beam has propagated through strongly turbulent regions,
      with structure parameters C(n)2 as many as 5 orders of magnitude larger than
      those encountered in the usual atmospheric conditions. Moreover, the filament's
      position within the beam is not affected by the interaction with a turbulent
      region. This remarkable stability is allowed by the strong Kerr refractive-index
      gradients generated within the filament, which exceed the turbulence-induced
      refractive-index gradients by 2 orders of magnitude.

PMID- 16419887
TI  - Major improvements of the photorefractive and photovoltaic properties in
      potassium niobate.
AB  - Optical and electrical measurements have been made on a new codoped potassium
      niobate crystal (KNbO3:Fe,Ag) that yields a significant enhancement of the
      photorefractive and photovoltaic effects when compared with the published results
      for singly doped potassium niobate crystals. The codoped Ag impurity enters the K
      site, rather than the typical Nb site, thus changing the local field in the
      lattice. It is believed that Fe perturbed by the Ag in the K site is responsible
      for an enhancement of the linear absorption and photocurrent, as well as a
      probable increase in the effective trap density. An enhanced trap density is
      likely the cause of the increased photorefractive counterpropagating two-beam
      coupling efficiency.

PMID- 16419888
TI  - White-light whispering gallery mode resonators.
AB  - We propose theoretically and demonstrate experimentally white-light whispering
      gallery mode resonators. These resonators have essentially a continuous modal
      spectrum accompanied by ultrahigh-Q frequency-independent quality factors.
      Applications of the resonators for ringdown spectroscopy and light modulation are
      discussed.

PMID- 16419889
TI  - Bandpass left-handed material optical filter with enhanced stop band rejection.
AB  - It is shown that a layer of left-handed media can act as a bandpass filter with a
      roll factor that far exceeds those of state-of-the-art spectral filters. The
      conditions for enhanced stop band rejection are presented and are deemed
      feasible, as the models used correspond to physically realizable materials. Roll
      factors of the order of 10(4)-10(6) dB/GHz are found, together with acceptable
      insertion losses of the order of 10 dB.

PMID- 16419890
TI  - Plasmon-polariton transport in metal-nanoparticle chains embedded in a gain
      medium.
AB  - Plasmon-polariton transport on chains of noncontacting noble-metal nanoparticles
      suffers from severe attenuation. A possible way of countering the attenuation by
      embedding the nanoparticle chain in an optical-gain medium is considered. It is
      found that short-wavelength surface polaritons can acquire exponential growth
      that can counter nonradiative loss. This is most pronounced for modes polarized
      transverse to the chain axis immediately outside the light line; this growth
      factor is likely to be sufficient to counterbalance losses and so lead to low
      attenuation propagation of plasmon polaritons in nanoparticle chains.

PMID- 16419891
TI  - Giant lateral shift of a light beam at the defect mode in one-dimensional
      photonic crystals.
AB  - It is found that when a light beam is incident on a one-dimensional photonic
      crystal (1DPC) containing a defect layer, the lateral shifts of both the
      reflected and the transmitted beams are greatly enhanced near the defect mode of
      the 1DPC, whose location depends on the angles at a fixed frequency. The effect
      was studied by use of a Gaussian beam. The giant lateral displacement is due to
      the localization of the electromagnetic wave.

PMID- 16419892
TI  - Generalized eikonal treatment of the Gouy phase shift.
AB  - We use a generalized refractive index that includes diffraction effects to show
      that the Gouy phase shift can be seen as an intensity averaged optical path
      difference between the generalized eikonal and the geometrical eikonal. This
      approach generalizes previous treatments to include the effects of phase
      distortion and confirms the role of transverse spatial confinement in the Gouy
      shift.

PMID- 16419893
TI  - Interconvertibility of single-rail optical qubits.
AB  - We show how to convert between partially coherent superpositions of a single
      photon with the vacuum by using linear optics and postselection based on homodyne
      measurements. We introduce a generalized quantum efficiency for such states and
      show that any conversion that decreases this quantity is possible. We also prove
      that our scheme is optimal by showing that no linear optical scheme with
      generalized conditional measurements, and with one single-rail qubit input, can
      improve the generalized efficiency.

PMID- 16419894
TI  - Quantum noise frequency correlations of multiply scattered light.
AB  - Frequency correlations in multiply scattered light that are present in quantum
      fluctuations are investigated. The speckle correlations for quantum and classical
      noise are compared and are found to depend markedly differently on optical
      frequency, which was confirmed in a recent experiment. Furthermore, novel
      mesoscopic correlations are predicted that depend on the photon statistics of the
      incoming light.

PMID- 16419895
TI  - Single-shot two-dimensional spectrometer.
AB  - A two-dimensional optical spectrometer is demonstrated using simple optical
      components. This spectrometer is based on ultrafast two-dimensional (2D)
      frequency-dispersed pump-probe spectroscopy and can be used for single-shot
      correlation spectroscopy. To demonstrate functionality of this device, we measure
      the 2D correlation spectrum of atomic rubidium.

PMID- 16419896
TI  - Femtosecond microscopy of radial energy transport in a micrometer-scale aluminum
      plasma excited at relativistic intensity.
AB  - Using femtosecond microscopy, we observe subpicosecond transport of thermal
      energy radially outward from a micrometer-sized spot of an aluminum target
      following P-polarized excitation at >10(18) W/cm2 with a 24 fs pulse. The rapid
      expansion coincides with the onset of nonlocal energy transport dominated by
      radiation and hot electrons.

PMID- 16419897
TI  - 47-fs diode-pumped Yb3+:CaGdAlO4 laser.
AB  - The experimental demonstration of a diode-pumped passively mode-locked
      femtosecond laser based on an Yb3+:CaGdAlO4 single crystal is reported. The
      oscillator is directly diode pumped by a high-brightness 5 W fiber coupled laser
      diode, and pulses are produced by use of a semiconductor saturable-absorber
      mirror. It permits the production of pulses as short as 47 fs at 1050 nm, which
      are to our knowledge the shortest laser pulses obtained from an oscillator based
      on Yb3+-doped bulk materials. The average power is 38 mW, and the repetition rate
      is 109 MHz.

PMID- 16419898
TI  - Sensitive ultrashort pulse chirp measurement.
AB  - The chirp of an ultrashort laser pulse can be extracted with high accuracy from a
      modified spectrum auto-interferometric correlation waveform by using a new time
      domain algorithm that allows signal averaging. We display results revealing high
      sensitivity to chirp even with signal-to-noise levels approaching unity.
      Correction algorithms have been developed to accommodate signal distortion
      arising from bandwidth limitations, interferometer misalignment, and nonquadratic
      detector response.

PMID- 16419899
TI  - Megahertz optical parametric amplifier pumped by a femtosecond oscillator.
AB  - We demonstrate, for the first time to our knowledge, an optical parametric
      amplifier directly pumped by a femtosecond oscillator. Wavelength-tunable pulses
      in the ranges 0.65-0.85 microm (signal) and 1.4-2.5 microm (idler) are generated
      at a repetition frequency of 1 MHz. For pumping the beta-barium borate crystal we
      use a microjoule Yb:KY(WO4)2 femtosecond oscillator with cavity dumping. Pulses
      with 30 nJ of energy and a duration of 16 fs are achieved from a supercontinuum
      seed generated in a sapphire plate.

PMID- 16419900
TI  - [Management in case of pandemia of H5N1 avian influenza].

PMID- 16419901
TI  - [Tuberculous abscess of the psoas].

PMID- 16419902
TI  - [How to reduce the risk of Legionnaires' disease?].
AB  - Legionella pneumophila is a microorganism present in water and able to develop
      pneumoniae through inhalation of contaminated aerosols. Legionnaires'disease is
      rare (1000 cases per year in France) concerning particularly people with risk
      factors, but potentially with severe prognosis (lethality 15-20%). The diagnosis
      was recently facilitated by the introduction of urinary antigen test. Hospital is
      the most frequent place where L. pneumophila were acquired; however the
      proportion of nosocomial cases is decreasing since 2001. The associated mortality
      is higher for hospital acquired cases than for community acquired cases. Several
      official guidelines were written about prevention of legionnaires' disease.
      Primary prevention is essentially based on control and maintaining of water
      distribution system. Secondary prevention should be a prompt response to
      identification of a case in order to find the source of Legionella and to protect
      immunocompromised persons.

PMID- 16419903
TI  - [Sanitary risk and new exigencies in health protection].

PMID- 16419904
TI  - [Protocols of health security in the light of some examples of risk management].
AB  - Throughout medical training, medical risk management is a subject that has been
      insufficiently addressed and treated without a global vision. Yet the different
      dangers often make the front page of a media that addresses the question of
      health security when there is a failure of the system or new legal developments.
      Added to this disequilibrium of communication and training is the great
      complexity of risk management. Not only is the nature of the potentially
      dangerous agents extraordinarily varied but also the entity that detects the risk
      is sometimes a stranger to the causes of its appearance. The surrounding
      regulations are themselves complex and dense. Using the examples that have arisen
      over the last 2 or 3 years, this article describes the current French protocols
      in risk management, that rely upon the agencies delivering their expertise,
      certain of which are endowed with the power of policing these regulations. In
      practice, the doctor should understand the role of these agencies, know how to
      find the validated information that they can provide, and understand his role in
      this picture. A role that is perceived as far away as long as the risk has not
      emerged, but is in the forefront once the event arises.

PMID- 16419905
TI  - [Infectious diseases risk management].
AB  - Surveillance activities first target health problems for which treatment,
      effective prevention or control measures are available. The data produced by
      surveillance systems allow prioritising public health actions and defining the
      objectives of infectious diseases control or prevention. The surveillance of
      infectious diseases relies on a large number of partners grouped in a public
      health network in which clinicians have a prominent role. In France, the
      surveillance of infectious diseases is based on mandatory notification of some
      diseases, national reference centers, networks of voluntary health professionals
      and repeated surveys, alerting health authorities in case of threats and
      identifying the determinants of changes in the population health's status. At
      hospital, the infectious risk is significant and the risk of epidemic outbreaks
      very high. A solid system for surveillance is mandatory. An educational program
      is needed to define the prevention program based on the use of hand disinfection
      and other standard precautions, antiviral and pneumococcal vaccination. A strong
      cooperation between general practitioners, healthcare team and relatives is
      necessary.

PMID- 16419906
TI  - [The practitioner's role in surveillance and information on environmental risks].
AB  - Health scares have entailed an increasing concern about environmental risks for
      populations. Authorities' response was to set up a system for the analysis,
      surveillance and management of environmental risks. Practitioners have an
      important role to play in this system, as primary actors of surveillance and as a
      close source of information about the environmental risks for the population.
      Three examples are developed. Children's lead poisoning still exists and entails
      irreversible neuropsychic deficits. Its diagnosis rests upon the recognition of
      risk factors and the prescription of a test of blood lead level. Carbon monoxide
      poisoning is the first cause of mortality by acute poisoning in France and it
      causes several thousand hospitalizations every year. Notification of the cases of
      lead and carbon monoxide poisonings is indispensable to remove their causes.
      Links between cancer and environment are an important social concern and a public
      health issue. Practitioners have a key role to play not only in the communication
      on this subject, but also to notify disturbing sanitary events and participate in
      the local investigations.

PMID- 16419907
TI  - [Sanitary risk: medicinal products and medical devices].
AB  - Health products at large and medicinal products in particular, relieve treat and
      restore through a pharmacological action on human body which might bear a part of
      risk. Therefore, medicinal products' effects are not considered once when the
      product comes to the market but permanently through its life. The benefit/risk
      ratio evolves from day to day according to the development of scientific
      knowledge and the feedback we have from the use of products in their real
      conditions of use. The ratio is assessed differently depending on the severity
      degree of the disease to be treated. The cursor, and then the risk level which
      can be acceptable and accepted, changes over time for the same kind of diseases
      along with therapeutic progress. The renewal and strengthening of post-marketing
      authorization surveillance is based on the early adoption of risk management
      programs for products with high security expectations.

PMID- 16419908
TI  - [Viral safety concept: application to blood and blood products].
AB  - Safety of blood and its derivatives, with regards to the risk of transmission of
      infectious agents such as viruses or non conventional agents, relies on a series
      of general principles for which national and European guidance and regulations
      have been drawn and regularly updated. Three main criteria contribute to the
      safety of these products: knowledge and control of the quality of blood or plasma
      as the starting material, the efficiency of the manufacturing process to
      remove/inactivate adventitious agents, and the testing done during the production
      process. In addition, vigilance routinely exercised on the products used in daily
      practice increases the confidence in these health products.

PMID- 16419909
TI  - [How to apply the 4th March 2002 French law, making information to patients
      mandatory after the identification of a new risk?].
AB  - The 4th March 2002 French law, through its L. 1111-2 article, makes it mandatory
      to inform persons who received medical care, investigation or preventive
      intervention when a new risk is identified after the act was done. The article L.
      1413-13 of the law adds that health authorities can summon responsible
      professionals if they establish a lack of information, unless it is impossible to
      find again exposed patients. The text relates conclusions of the working group
      set up in 2003 by the Chief Medical Officer whose mission was to identify what
      kind of situations fitted this new right and the consequences, in terms of
      action, of the qualification of an event as a "new risk". The two main outcomes
      were to clear up the basic ambiguity concerning the term of "new risk" and to
      propose a framework defining the multiple stages by which it has to be assessed.
      Furthermore, the diversity of potential situations to be faced in connection with
      the possible consequences of information raised the issue of objectives aimed by
      the lawmaker. Despite good intentions, the law as laid down appears insufficient
      to ensure that this new right will be always beneficial to the patients, in terms
      of public health.

PMID- 16419910
TI  - [Quality of care: and what about safety?].

PMID- 16419911
TI  - [National ranking exam. N12. What could fall at the exam?].

PMID- 16419912
TI  - [Irritable bowel syndrome].

PMID- 16419913
TI  - [Palpitations].

PMID- 16419914
TI  - [Acute diarrhea and dehydration in infants and children].

PMID- 16419915
TI  - [Deep venous thrombosis and pulmonary embolism].

PMID- 16419916
TI  - [Obstetrical auscultation in France in the 19th Century].

PMID- 16419917
TI  - Chinese solutions.
AB  - Following an extended visit to (China to discuss health (are technologies, a
      number of issues concerning the rapid growth in the country's biomaterials and
      medical technology sectors have become apparent. These developments deserve the
      attention of scientists and industrialists in the West.

PMID- 16419918
TI  - A proprietary approach to powering medical RF links.
AB  - A proprietary radio-frequency alternative, based on a custom application-specific
      integrated circuit design, can add wireless capability to medical devices without
      the overheads of other technologies. The advantages of a proprietary transceiver
      are compared here with Bluetooth and ZigBee using a pulse oximeter as an
      application example.

PMID- 16419919
TI  - Urinary incontinence: how technology can help.
AB  - A UK government-backed research centre has been established that specialises in
      new product development for urinary incontinence. Ideas and partners are sought.

PMID- 16419920
TI  - Useful US guidance on device software.
AB  - The use of software in medical devices and their accessories has led to
      significant improvements in clinical diagnosis and treatment of a vast range of
      illnesses. However, to benefit patients and users, device-related software must
      be properly developed and tested before use. This article discusses a United
      States guidance document that describes the type of documentation needed to show
      that this has been done.

PMID- 16419921
TI  - Annex II technical documentation assessed.
AB  - Annex II of the Medical Device Directive (MDD) is used frequently by
      manufacturers to obtain CE-marking. This procedure relies on a full quality
      assurance system and does not require an assessment of the individual medical
      device by a Notified Body. An investigation into the availability and the quality
      of technical documentation for Annex II devices revealed severe shortcomings,
      which are reported here.

PMID- 16419922
TI  - The threats and challenges of REACH.
AB  - The proposed Registration Evaluation and Authorisation of CHemicals (REACH)
      regulation, which aims to regulate the use of chemicals in the European Union,
      could have a severely damaging effect on the in vitro diagnostic industry as well
      as on public health. This article examines the issues.

PMID- 16419923
TI  - The complexity of compliance in IVD manufacturing.
AB  - To achieve optimum productivity and regulatory compliance, manufacturers need
      solutions that address manufacturing, regulatory and business needs
      simultaneously. Ways to reduce the costs and achieve regulatory compliance are
      presented here.

PMID- 16419924
TI  - Designing screened enclosures: part I.
AB  - Part I of this two-part article addresses the basic theory of screening and
      outlines the choice of gasket and methods that can be employed to create a
      successful enclosure.

PMID- 16419925
TI  - Tissue engineering skin: a paradigm shift in wound care.
AB  - Tissue-engineered skin for the treatment of burns and ulcers is a clinical
      success, but making it commercially viable is more problematic. This article
      examines the industry, its techniques and suggests the way forward.

PMID- 16419926
TI  - The industry moves confidently into 2006.

PMID- 16419927
TI  - Next-generation wireless monitoring for body and mind.
AB  - Next-generation remote-monitoring devices may achieve the dual goals of boosting
      the effectiveness of the healthcare sector as a whole and empowering users to
      take control of their health status. One technology centre, operating an open
      innovation partnership model, is looking for partners to be involved in
      developing a generic smart technology platform that will make this goal a
      reality.

PMID- 16419928
TI  - The NHS needs innovation, not patient care on-the-cheap.
AB  - One year after the publication of the Healthcare Industries Task Force report the
      medical device technology industry has mixed emotions.

PMID- 16419929
TI  - Irish medical device industry update.
AB  - The continued growth of the Irish medical technology industry has not been
      accidental. The sector is proactive in its drive for excellence in all aspects of
      the business, from concept to commercialisation. This reports on some recent
      initiatives.

PMID- 16419931
TI  - [Algorithm for automatic quantification of brain atrophy with computed
      tomography].
AB  - In this paper, a new, fully-automatic method for the quantification of brain
      atrophy based on CT volume data is put forward by taking advantage of the
      characteristics of cerebral CT images in combination with the prior medical
      knowledge. This algorithm has been verified through the calculation of 2388 cases
      of normal and brain atrophy subjects.

PMID- 16419930
TI  - [Immunological evaluation of biomaterials and medical devices].
AB  - The immunoreaction caused by biomaterials or medical devices are even more
      concerned by people. It is necessary to establish the immune items in the
      biological evaluation of biomaterials and medical devices. And it is a tendency
      to use immune technique combined with molecular biological methods to evaluate
      the immunoreaction for biomaterials.

PMID- 16419932
TI  - [A monitoring technique in detecting the depth of anesthesia by bispectral
      index].
AB  - At the present time, a kind of monitoring technology assuring highly effectual
      anesthesia is urgently required in the clinical practice. Electroencephalogram
      (EEG) assumes a dominant position in the current research of the depth detection
      of anesthesia. In this paper, the monitoring technique of the depth detection of
      anesthesia by bispectral index (BIS) is systematically showed. The bispectral
      index is a compound parameter which is composed of time domain, frequency domain,
      and high order spectral subparameters of the electroencephalograph. This
      nonlinear compound calculation method is worth research and is of great
      significance to the development of a new monitor of closed-loop control of
      anesthesia.

PMID- 16419933
TI  - [Application of syntactic pattern recognition in research on pulse wave's
      characteristic information].
AB  - In this paper, a syntactic pattern recognition method of the detection of pulse
      wave's characteristic information is introduced. According to it, the pressure
      signal of pulse is measured by non-invasive diagnostic method. Then, the
      elementary abstracting system transfers it into an input pattern. The recognizer,
      constructed by Earley algorithm, recognizes the pulse wave's pattern. On the base
      of it, the pulse wave's characteristic information can be got. Thus, the expert
      system will make a diagnosis with the information. The experiment result shows
      that, the new method is of anti-interference, preciseness and intelligence, and
      it provides an advanced, practical and intelligent means for the pulse diagnostic
      system.

PMID- 16419934
TI  - [Research on swallowable camera-capsules of gastrointestinal wireless endoscope].
AB  - The swallowable camera-capsule,described in the aper, 11 mm in diameter and 30 mm
      in length , contains a CMOS image sensor, an optical system, a battery, a light
      source, a transmitter, a antenna and so on. The CMOS image sensor and its driving
      circuit can be miniaturized with MEMS technology. Image signal can be transmitted
      by analog or digital way. Image signal can be wirelessly transmitted through
      serial data interface. Finally, the processing technics of the capsule's crust is
      introduced.

PMID- 16419935
TI  - [Development of an apparatus for preventing deep vein thrombosis].
AB  - A kind of intermittent pneumatic compression (IPC) apparatus is developed to
      prevent deep vein thrombosis (DVT),which is based on the theory of occurrence and
      prevention of the DVT and AT89C52 micro-controller. This paper introduces its
      principle, composition of electromechanical system and the software design. The
      apparatus has showed its characteristics of easy operation, high intelligence and
      high reliability.

PMID- 16419936
TI  - [Development of a pathological information network and image analysis system].
AB  - This paper introduces a pathological information network and image analysis
      system designed by ourselves. The system offers an efficient means for modern
      medical diagnosis and treatment, teaching, research and management in the
      department of pathology.

PMID- 16419937
TI  - [Development of WY21A interference fringe visuometer and its clinical
      applications].
AB  - WY21A Interference Fringe Visuometer, based on Thomas Young's interference
      theory, uses grating to produce interference lamp-house. This compact, flexible
      machine could be applied to measure interference fringe visual acuity. Its
      clinical tryout shows that WY21A is suited for daily practice as it is able to
      give a fast, easy and reliable preoperative assessments and prediction of visual
      recovery for most age-related cataract patients.

PMID- 16419938
TI  - [Research on ECG-monitoring based on the technology of virtual instruments].
AB  - A ECG-monitoring system based on the technology of virtual instruments, has been
      developed. Its advantages involve real-time ECG-display and alarm for abnormal
      heart rate,low cost and flexibility of function-expanding . And most functions of
      the system are completed by software instead of hardware. The preliminary
      experimental results indicate that the system's delay time is less than 2 s,
      meeting the requirements of real time monitoring.

PMID- 16419939
TI  - [Invert transformer design for high frequency X-ray machine based on PWM
      controller SG 3525].
AB  - This paper introduces the principle of invert transformer of high frequency X-ray
      machine, and analyzes its main constitution. Meanwhile, a scheme based on SG3525
      for closed loop voltage regulation is given. The experimental result testifies
      its efficiency and utility.

PMID- 16419940
TI  - [An arrhythmia ECG analog signal generator using standard MIT-BIH arrhythmia
      database].
AB  - Microchip MSP430F149 is used to control DAC to attain an amplification
      controllable analog output of data of MIT-BIH Arrhythmia Database which is useful
      in testing medical machines. Data are written into Smart Media (SM) Card with Fat
      Format to make convenient the replacement of database.

PMID- 16419941
TI  - [Research on metrological verification and the development of the verification
      equipment for digital electrocardiographs].
AB  - In order to guarantee that digital electrocardiographs with an adequate accuracy
      and reliabity are available for measurements in clinical practice, it is very
      important to determine the metrological characteristics, methods and to develop
      the equipments for verification. This paper elaborates the basic functions,
      specification, schematic drawing and key techniques of calibration equipments as
      well as test items for digital electrocardiographs.

PMID- 16419943
TI  - [A review of brain-computer interfaces (BCIs)].
AB  - This paper introduces the general constitutions and principle of BCI systems. In
      addition, some characteristics and limitations of different research methods are
      discussed and compared. Finally, this paper points out the existing problems and
      future trends of BCIs. brain-computer interface (BCI), human-computer Interface
      (HCI), electroencephalography (EEG).

PMID- 16419942
TI  - [A special instrument for hematocrit measurement].
AB  - A new instrument for hematocrit measurement is introduced in the paper, which can
      get the same accurate Hct values while its centrifuging speed is reduced. It
      integrates high speed centrifuge, automatic data processing and automatic
      analysis of hematocrit into a system, having more advantages than the traditional
      measuring devices, such as lower noise, less test errors and better accuracy.
      Therefore, it can satisfy well clinical applications.

PMID- 16419945
TI  - [Innovative ultrasound transducers-purewave crystal technology and its
      applications].
AB  - This article is to introduce the dramatic improvements in efficiency, sensitivity
      and bandwidth of the ultrasound transducers--PureWave Crystal Technology.

PMID- 16419944
TI  - [An electromagnetic navigation system in interventional radiology].
AB  - This paper introduces the operation principle, experimental research and clinical
      applications of an electromagnetic navigation system in interventional radiology
      and looks forward to the prospects for its clinical applications.

PMID- 16419946
TI  - [Development and actuality of patient monitoring products in our country].
AB  - A new specialty and trend of the clinical patient monitoring products have
      appeared. They include the consciousness of clinical monitoring, the product
      supply, the functional expansion, the application of new techniques in the
      patient monitoring and the development of the clinical information system (CIS).

PMID- 16419947
TI  - [Existant quality problems and suggestions for quality control of medical
      absorbent cotton].
AB  - In the process of acid hydrolysis of medical absorbent cotton, we have discovered
      that some of the domestic manufactured medical absorbent cotton is mixed with
      wasted non-cotton chemical fiber. If the cotton is used in medical treatments,
      the chemical fiber will cause irritation, allergy and inflammation, so it's very
      harmful. But the non-cotton fiber content is not stipulated in the standard of
      YY0330-2002, and no testing method for it is available. In this paper we discuss
      the existent quality problems, the control and the test method for non-cotton
      chemical fiber in medical absorbent cotton.

PMID- 16419949
TI  - [Clinical applications of noninvasive positive pressure mechanical ventilation
      technology].
AB  - This article expounds the types, applicable diseases and medical departments of
      noninvasive positive pressure mechanical ventilators and the problems we should
      pay attention to while using them.

PMID- 16419948
TI  - [Research on the laser atomization treatment machine].
AB  - This text has introduces a new-type laser treatment device. It utilizes the
      ultrasound atomized gas passage as its optics and makes the laser beams together
      with the atomized medicine to be transmitted to the patient's respiratory track
      and lungs for treatment.

PMID- 16419950
TI  - [Centralized management strategy of the infant incubators in NICUs].
AB  - There are many problems existing at present in the incubator applications and
      management. Among them, the prominent problems are their cleaning and
      disinfection. We hope to find, through the centralized management and clinical
      engineering, an efficient strategy in order to get more reasonable and better
      maintenance, cleaning and training for infant incubators in NICUs. Scientific
      management will provide an excellent service to infant patients.

PMID- 16419951
TI  - [The misdiagnosis of congenital cholesteatoma of the temporal bone (5 case
      report)].
AB  - OBJECTIVE: The congenital cholesteatoma of the temporal bone is a rarer disease
      which might easily be misdiagnosed and wrongly treated. The clinical material and
      management of five cases are hereby introduced in order to call common attention.
      METHOD: There were 4 males and 1 female with age rage 10-48 years old. All cases
      revealed intact drum membrane. The complaints of these 5 cases are: 2 cases
      suffered from facial palsy; 2 cases from purulent bloody otorrhea; 1 case from
      otalgia. Among these five congenital cholesteatomas, four cases were originated
      from petromastoid region and 1 case from undeveloped. external ear canal.
      Surgical managements were performed after preoperative radiological examination
      in these five cases. RESULT: In each case, the diagnosis was confirmed by
      pathological examination and the disease was cured by operation. CONCLUSION: If a
      patient is suffered from facial palsy or otorrhea or otalgia, but the eardrum is
      intact, the correct diagnosis and suitable treatment of the congenital
      cholesteatoma are easily to be delayed and failed. Radiological evaluation,
      carefully topical examination and paying attention to this disease play important
      role in the early diagnosis and surgical management, thus the serious
      complications might be avoided.

PMID- 16419952
TI  - [Auditory brainstem response in severe obstructive sleep apnea-hypopnea syndrome
      children].
AB  - OBJECTIVE: To explore the characteristics of auditory brainstem response(ABR) in
      severe obstructive sleep apnea-hypopnea syndrome. METHOD: ABR was recorded in 37
      severe OSAHS patients (OSAHS group) and 20 controls. RESULT: (1) In the OSAHS
      group, the latency values of waves I, III and V were (1.67+/-0.20) ms, (3.87+/
      0.31) ms, (5.70+/-0.31) ms respectively. In the control group, the latency values
      of waves I, III and V were (1.60+/-0.11) ms, (3.81+/-0.23) ms, (5.61+/-0.23) ms
      respectively. A statistically significant prolongation was found in the latency
      values of waves I in OSAHS group compared to control group (P < 0.05). (2) When
      comparing to the control group, the transmission time between waves III and V was
      found to be prolonged and waves I and III to be shortened in the OSAHS group.
      Furthermore, the change was considered statistically significant (P <0.05). (3) A
      statistically significant elevation was found in response threshold of wave V
      when comparing to the control group (P < 0.05). CONCLUSION: The pathological
      sleepiness seen in OSAHS patients may cause ABR abnormalities, as a consequence
      of the chronic hypoxic and hypercapnic status occurring in the brain-stem and
      cochlear.

PMID- 16419953
TI  - [Long-term results analysis of mastoidectomy for chronic otitis media].
AB  - OBJECTIVE: To study the operative indications of chronic otitis media and their
      long-term results. METHOD: One hundred and forty-five cases of mastoidectomy were
      followed for 5 years between 1995-1998. We discussed the results of recurrence
      and hearing level of radical mastoidectomy, canal wall up mastoidectomy (CWUM)
      and canal wall down mastoidectomy with mastoid obliteration (CWDM). Advantages
      and disadvantages were analyzed by the rate of visiting. RESULT: RM is almost
      invariable in hearing. There is no significant difference between CWDM [improved
      (10.84+/-4.63) dB HL] and CWUM [improved (10.39+/-3.93) dB HL]. The recurrence
      rate of RM was 11.63%, CWDM was 12.68%, but the CWUM was 22.58%. Rate of re
      visiting of RM is obviously higher that of CWUM and CWDM. CONCLUSION: RM, CWUM
      and CWDM have all advantages, but the indication must be selected carefully. The
      effect of CWDM is better than that of RM and CWUM for the long-term results in
      these cases.

PMID- 16419954
TI  - [Surgical treatment of first branchial cleft anomaly].
AB  - OBJECTIVE: To identify the clinical and anatomical presentations and to discuss
      the guidelines for surgical management of anomalies of the first branchial cleft.
      METHOD: Twenty-one patients with first branchial cleft anomalies were treated in
      our department between January 1994 and December 2004, their clinical data were
      retrospectively analysed. RESULT: Surgery was performed on all patients. Among
      them 13 were males and 8 females, ranging in age from 1.5 to 33 years with an
      average of 15 years. Anatomically, 3 types of first branchial cleft anomalies
      were identified: fistulas (n = 17), cysts (n = 2), and fistula combined with cyst
      (n = 2). Before definitive surgery, soma patients (n = 4) underwent incision and
      drainage for infection owing to the difficulties in diagnosing this anomaly.
      Methylthioninium Chloride was used in almost all cases for tracking the fistulous
      during operation. Wide exposure is necessary in many cases,and a standard
      parotidectomy incision allows adequate exposure of the anomaly and preservation
      of the facial nerve. CONCLUSION: Complete removal without complications depends
      on a good understanding of regional embryogenesis, an awareness of the different
      anatomical presentations, and a readiness to identify and protect the facial
      nerve during resection.

PMID- 16419955
TI  - [Hearing intervention for > or =55 years old people with hearing impairment
      within five years recently].
AB  - OBJECTIVE: To investigate the status of hearing intervention for old people with
      hearing loss. METHOD: Through retrospective analyzing the data from 55 and up 55
      years old people with hearing loss who received hearing intervention in five
      years (from 2000 - 2004) recently. RESULT: There were 1008 person-times that
      received hearing examination within five years, 907 person-times speech frequency
      pure tone average (PTA) > 26 dB,there were only 73 people with hearing aid, and
      their speech frequency PTA > 55 dB. CONCLUSION: The hearing intervention
      situation for old people isn't perfect. It needs audiologists cooperate with the
      family of old people, the whole society and the old people themselves to help
      them in hearing and improve their quality of life.

PMID- 16419956
TI  - [Analysis of the characteristics of matching hearing aids in deaf children in
      Guangdong province].
AB  - OBJECTIVE: To explore the characteristics of matching hearing aids in different
      districts with various economic levels. METHOD: The deaf children were divided
      into two groups: one group came from district with poor economic level, another
      came from district with flourishing economic level. The age of first matching
      hearing aids, sex proportion, degree of hearing loss and type of hearing aids
      (digital/simulation) were analyzed. RESULT: (1) The average age of first matching
      hearing aids was 3.82 years old; male: female = 1.47:1. No significant difference
      was observed between two different district. (2) The proportion of deaf children
      whose response threshold of wave V was above 90 dBnHL was 86.36% in district with
      flourishing economic level, whereas it was 93.85% in district with poor economic
      level. (5) The proportion of deaf children whose first hearing aids were digital
      was 75.57% in district with flourishing economic level. It was 65.38% in district
      with poor economic level. CONCLUSION: A significant correlation is found between
      characteristics of matching hearing aids and economic level. The reason that the
      difference of sex proportion is enormous must be studied in further studies.

PMID- 16419957
TI  - [Analysis of audiological assessment and hearing aid evaluation results from 13
      deaf children].
AB  - OBJECTIVE: To investigate why the ideal objective cannot be met after deaf
      children are fitted with hearing aids. METHOD: Complete audiological assessment
      and hearing aid check were done on 13 deaf children filled with hearing aids.
      RESULT: Two children were found to have otitis media with effusion and myringitis
      respectively. All hearing aids were matched improperly with inappropriate fit.
      CONCLUSION: After deaf children are fitted with hearing aids, they should be
      followed-up on a regular base in order to monitor their hearing and to check
      whether they wear the hearing aids properly with a proper fit. All people in the
      field of aural rehabilitation for deaf children should realize the importance of
      the correct way to wear hearing aids with correct adjustment.

PMID- 16419959
TI  - [Expression and its significance of aquaporins in normal guinea pig inner ears].
AB  - OBJECTIVE: To investigate the expression and its significance of aquaporins
      (AQPs) in normal guinea pig inner ears. METHOD: Ten healthy guinea pigs were
      used. Immunohistochemistry were employed to detect AQP0, 1, 2, 3, 5, 7, 8 in
      normal guinea pig inner ears,using rabbit anti-rat polyclonal antibodies. RESULT:
      AQP0, 1, 2, 3, 5, 7, 8 were all expressed in guinea pig inner ears. AQP0 was only
      located in stria vascularis and spiral ganglion. The distribution of AQP1
      consisted of cells lining the bony labyrinth, fibrocytes lining the endolymphatic
      duct and sac, cells under the basilar membrane, fibrocytes of the spiral ligament
      and the spiral limbus,Corti's organ, inner and outer spiral sulcus, stria
      vascularis, saccular and utricular wall, and spiral ganglion. AQP2 located in
      stria vascularis, Corti's organ, spiral ganglion and endolymphatic sac. AQP3,7,8
      distributed in a similar manner which was surrounding the membranous labyrinth,
      including Corti's organ, inner and outer spiral sulcus, stria vascularis,
      fibrocytes of the spiral ligament and the spiral limbus, saccular and utricular
      wall, endolymphatic sac and spiral ganglion. AQP5 located at Corti's organ, inner
      and outer spiral sulcus, spiral ganglion, fibrocytes in spiral ligament.
      CONCLUSION: Diverse AQPs are distributed in the normal guinea pig inner
      ears,which may co-work to maintain the homeostasis of the inner ear.

PMID- 16419958
TI  - [The diagnosis and therapy for cholesterol granuloma of middle ear].
AB  - OBJECTIVE: To explore the diagnosis for cholesterol granuloma of middle ear, and
      discuss the effect of middle ear surgery for this disease. METHOD: The files of
      18 patients (19 ears) with cholesterol granuloma of middle ear were reviewed in a
      retrospective study. All patients received middle ear and mastoid surgery, and
      all involved tissues were verified as cholesterol granuloma by pathologic
      examination. RESULT: The patients undergoing ventilation tube insertion were
      extubated 1-3 months after surgery and the eardrums healed well. The eardrums of
      the patients without ventilation tube insertion became normal 1-2 months after
      surgery. The hearing threshold after surgery of all patients improved. Beside one
      patients with eustachian tube obstructed had ventilation tube inserted with long
      term, no patient had symptoms recurred. CONCLUSION: The cholesterol granuloma of
      middle ear results from the bleeding, occlusion of ventilation and disturbance of
      drainage of the air cavity because of the middle ear inflammation. The diagnosis
      depends on the pathological examination. The middle ear and mastoid surgery,
      removing the diseased tissues completely, creating a ventilation system of
      mastoid-tympani-Eustachian are the key

PMID- 16419960
TI  - [Apoptosis and its molecular mechanism in vestibular hair cell after gentamycin
      toxicity].
AB  - OBJECTIVE: To investigate the character of damaged vestibular hair cells caused
      by gentamycin, and to identify whether apoptosis and phosphorylation of JNK
      occurs in the damaged cells. METHOD: Healthy guinea pigs were divided into
      experimental group and control group randomly with 15 in each group, animals in
      experimental and control group received systemic injection of gentamycin [100
      mg/(kg x d)] and saline respectively for 7 consequent days. All the animals were
      sacrificed on the 8th day, the crista vestibular of each were observed by
      preparation and frozen dissection. The apoptosis of hair cell were detected by
      TUNEL method and phosphorylation of JNK were detected by immunochemistry. RESULT:
      The lesion and apoptosis of hair cells could be seen in the experimental
      group,and the phosphorylation could be observed too; the hair cells of control
      group showed no sign of apoptosis or phosphorylation of JNK. CONCLUSION:
      Gentamycin cause vestibular hair lesion by inducing apoptosis and activation of
      JNK plays an important role in the procedure of apoptosis.

PMID- 16419961
TI  - [Apoptosis and dynamic caspase-3 expression during the immune response of inner
      ear].
AB  - OBJECTIVE: To investigate whether apoptosis is involved in the pathogenesis of
      the immune response of inner ear, and relation between signal transportation of
      Caspase-3 and apoptosis. METHOD: Forty-five healthy, female white guinea pigs
      were employed in this study. Sensitized systematically with keyhole limpet
      hemocyanin (KLH), the KLH-immunized animals were inoculated with the same
      antigen, and the control animals were injected PBS through cochlea basal turn.
      All animals were sacrificed respectively at 1st, 3rd, 5th, 7th and 14th day after
      inner ear vaccination. The auditory brainstem response (ABR) was measured before
      the KLH injection to the inner ear and just before sacrificing the animal.
      Paraffin sections of cochleas from animals were stained using a TUNEL assay to
      identify inner ear cells undergoing apoptosis,and immunohistochemistry method was
      used to detect the expression of Caspase-3 in the inner ears. RESULT: After
      immunization, the ABR thresholds of the KLH-challenged ears were significantly
      elevated by comparing with the preimmunization (P < 0.05), but after injection,
      there was no significant difference in the ABR thresholds of the PBS-injected
      ears compared with preinjection. TUNEL-positive cells were found in the KLH
      immunized inner ears but no TUNEL-positive cells were observed in the control
      inner ears except for a few positive cells in the supporting cells, the stria
      vascularis cells and the spiral ganglion cells. The positive cells are the outer
      hair cells in Cortis organ, and the marginal cells in the stria vascularis and
      the neurons in the spiral ganglion. And, under morphological analysis by light
      microscope, these cells have the features characteristic of apoptosis. Apparent
      Caspase-3 immunoreactivity expression could be detected in Corti's organ, the
      lateral wall and the neurons of the spiral ganglion in the KLH-immunized inner
      ears from 5th day after inner ear vaccination, but no cells staining positive for
      Caspase-3 were found in the control inner ears. CONCLUSION: Apoptosis is induced
      by the immune response of inner ear; Caspase-3 cascade has important effect on
      the course of apoptosis.

PMID- 16419963
TI  - Effect of pulsed electromagnetic fields on maturation of regenerate bone in a
      rabbit limb lengthening model.
AB  - To study the effect of applying pulsed electromagnetic fields (PEMF) during the
      consolidation phase of limb lengthening, a mid-tibial osteotomy was performed in
      18 adult New Zealand White rabbits and an external fixator was applied
      anteromedially. Animals were randomly assigned to treatment and control groups.
      After a 7-day latency period, the tibiae were distracted 0.5 mm every 12 h for 10
      days. The treatment group received a 20-day course of PEMF for 60 min daily,
      coinciding with initiation of the consolidation phase. The control group received
      sham PEMF. Radiographs were performed weekly after distraction. Animals were
      euthanized 3 weeks after the end of distraction. Radiographic analysis revealed
      no significant difference in regenerate callus area between treatment and control
      tibiae immediately after distraction, at 1 week, 2 weeks, or 3 weeks after
      distraction ( p = 0.71, 0.22, 0.44, and 0.50, respectively). There was also no
      significant difference in percent callus mineralization ( p = 0.96, 0.69, 0.99,
      and 0.99, respectively). There was no significant difference between groups with
      respect to structural stiffness ( p = 0.80) or maximal torque to failure ( p =
      0.62). However, there was a significant positive difference in mineral apposition
      rate between groups during the interval 1-2 weeks post-distraction ( p < 0.05).
      This difference was no longer evident by the interval 2-3 weeks post-distraction.
      While PEMF applied during the consolidation phase of limb lengthening did not
      appear to have a positive effect on bone regenerate, it increased osteoblastic
      activity in the cortical bone adjacent to the distraction site. Since the same
      PEMF signal was reported to be beneficial in the rabbit distraction osteogenesis
      when applied during distraction phase and consolidation phase, application of
      PEMF in the early phase may be more effective. Further work is necessary to
      determine optimal timing of the PEMF stimulation during distraction osteogenesis.

PMID- 16419964
TI  - Recombinant human BMP-7 effectively prevents non-union in both young and old
      rats.
AB  - The purpose of this study was to evaluate the influence of age on the
      effectiveness of rhBMP-7 treatment in a fracture with severe periosteal damage
      that is known to result in non-union formation. Closed stabilized femur fractures
      were produced in 3-month-old and 18-month-old rats. The fracture site was exposed
      and 2 mm of the periosteum cauterized circumferentially to impair normal fracture
      healing. The cauterized fracture site was immediately treated with either 100
      microg rhBMP-7 (BMP-7 group), or with 25 microL of vehicle alone (control group).
      Fracture healing was evaluated with radiographs taken at 3 and 6 weeks. Animals
      were sacrificed at 3 and 6 weeks and specimens subjected to biomechanical and
      histological evaluation. In both age groups, none of the control animals healed
      throughout the 6 weeks experimental duration. All of the rhBMP-7-treated 3-month
      old animals were radiographically healed at 3 weeks. In comparison, only 56%
      (9/16) of the rhBMP-7-treated 18-month-old animals were radiographically healed
      at 3 weeks. At 6 weeks, however, all of the 18-month-old rhBMP-7-treated animals
      had healed. Histology revealed slower healing in the 18-month-old animals.
      Treatment with rhBMP-7 significantly increased all of the biomechanical
      properties in both age groups. In the 3-month-old animals the mechanical strength
      approached that of the intact femur at 3 weeks, while in the 18-month-old animals
      this did not occur until 6 weeks. In conclusion, rhBMP-7 can effectively
      stimulate fracture repair in both young (3-month-old) and old (18-month-old)
      rats. However, the effect of rhBMP-7 on the rate of fracture healing is greater
      in young rats compared to old rats.

PMID- 16419965
TI  - Nonadherent cell population of human marrow culture is a complementary source of
      mesenchymal stem cells (MSCs).
AB  - To obtain enough quantity of osteogenic cells is a challenge for successful cell
      therapy in bone defect treatment, and cell numbers were usually achieved by
      culturing bone marrow cells in a relatively long duration. This study reports a
      simple and cost-effective method to enhance the number of mesenchymal stem cells
      (MSCs) by collecting and replating the nonadherent cell population of marrow MSCs
      culture. Bone marrow MSCs were isolated from 11 patients, cultured at a density
      of 1 x 10(5)/cm(2) to 1 x 10(6)/cm(2) in flasks. For the first three times of
      media change, the floating cells were centrifuged and replated in separate
      flasks. The total number of cells in both the primary and replating flasks were
      counted at day 21. Cell proliferation rate, potentials for osteogenic,
      chondrognenic, and adipogenic differentiation were examined in both cell types in
      vitro. In vivo osteogenic potentials of the cells were also tested in mice
      implantation model. The results showed that MSCs derived from nonadherent cell
      population of marrow cell cultures have similar cell proliferation and
      differentiation potentials as the originally attached MSCs in vitro. When
      implanted with hydroxyapatite/tricalcium phosphate (HA-TCP) materials
      subcutaneously in serve combined immune deficiency (SCID) mice, newly formed bony
      tissues were found in both cell type groups with osteocalcin expression. We have
      obtained 36.6% (20.70%-44.97%) more MSCs in the same culture period when the
      nonadherent cell populations were collected. The findings confirmed that the
      nonadherent cell population in the bone marrow culture is a complementary source
      of MSCs, collecting these cells is a simple and cost-effective way to increase
      MSCs numbers and reduce the time required for culturing MSCs for clinical
      applications.

PMID- 16419966
TI  - Osteoclastogenesis in the nonadherent cell population of human bone marrow is
      inhibited by rhBMP-2 alone or together with rhVEGF.
AB  - During bone development and repair, angiogenesis, osteogenesis, and bone
      remodeling are closely associated processes that share some common mediators. In
      the present study nonadherent human bone marrow mononuclear cells under the
      induction of sRANKL and M-CSF, differentiated into osteoclasts with TRAP-positive
      staining, VNR expression, and Ca-P resorptive activity. The effects of various
      combinations of rhBMP-2 (0, 3, 30, and 300 ng/mL) and rhVEGF (0 and 25 ng/mL) on
      osteoclastogenesis potentials were examined in this experimental system. The
      percentages of TRAP-positive multiple nucleated cells represent osteoclast
      differentiation potential, and the percentages of resorptive areas in the Ca-P
      coated plates resemble osteoclast resorption capability. The presence of rhBMP-2
      at 30 and 300 ng/mL showed inhibitory effects on osteoclast differentiation and
      their resorptive capability in the human osteoclast culture system. rhVEGF (25
      ng/mL) enhanced the resorptive function of osteoclast whenever it was used alone
      or combined with 3 ng/mL rhBMP-2. However, rhVEGF-induced resorptive function was
      inhibited by 30 ng/mL and 300 ng/mL rhBMP-2 in a dose-dependent manner.
      Statistical analysis demonstrated that an interactive effect exists between rhBMP
      2 and rhVEGF on human osteoclastogenesis. These findings suggested that an
      interactive regulation may exist between BMPs and VEGF signaling pathways during
      osteoclastogenesis; exact mechanisms are yet to be elucidated.

PMID- 16419967
TI  - Reliability and validity of plain radiographs to assess angulation of small
      finger metacarpal neck fractures: human cadaveric study.
AB  - To quantify reliability and validity of plain radiographs for assessing the
      degree of small finger metacarpal neck fracture angulation, we created typical
      two-fragments fractures in 30 adult cadaveric specimens. Reliability and validity
      of different radiographic measurement methods were determined by the intraclass
      correlation coefficient (ICC) and the Bland and Altman graphical approach.
      Intraobserver and interobserver reliability was high with any radiographic
      measurement method. Mean ICCs values (95% confidence intervals) varied from 0.76
      (0.56-0.88) to 1.00 (0.99-1.00). The graphical approach confirmed good agreement.
      Validity was substantial when the fracture angle was measured between the line
      along the longitudinal axis of the metacarpal shaft and the line from the center
      of the metacarpal head to the fracture site on lateral radiographs. Mean ICCs
      values varied from 0.70 (0.36-0.86) to 0.79 (0.5-0.90). The graphical analysis
      also indicated good agreement. In contrast, considerable lack of validity was
      observed when the angle was measured on oblique radiographs. Although the mean
      ICCs values varied from 0.68 (0.12-0.88) to 0.74 (0.05-0.90), suggesting
      substantial correlation, the graphical analysis provided evidence for poor
      validity. There was systematic bias with oblique radiographs consistently
      producing higher readings (up to 35 degrees ). In summary, reliability and
      validity are good only when the degree of small finger metacarpal neck fracture
      angulation is measured after drawing lines on lateral radiographs. Oblique
      radiograph measurements consistently produce higher readings.

PMID- 16419968
TI  - Alumina particles influence the interactions of cocultured osteoblasts and
      macrophages.
AB  - The purpose of the current study was to evaluate the effects of alumina particles
      on secretion of several cytokines involved in bone resorption in cocultures of
      macrophages and osteoblasts. To distinguish the contribution of each individual
      cell type, we have established a heterologous in vitro system that makes use of
      mouse J774 cells and primary cultured human osteoblasts. J744 cells decreased the
      production of TNF-alpha when they were cocultured with osteoblasts. Treatment of
      J744 cells with alumina particles increased TNF-alpha secretion, but the
      induction was lower when cells were cocultured with osteoblasts. Secretion of IL
      6 by J744 cells was very low, and increased in the presence of osteoblasts.
      Alumina particles were only able to stimulate the release of IL-6 by J744 cells
      when cells were cocultured with osteoblasts. On the other hand, incubation of
      osteoblasts with alumina particles enhanced the release of IL-6 and GM-CSF.
      Coculturing osteoblasts with J744 cells induced them to release IL-6 and GM-CSF,
      and treatment with alumina further increased the secretion of both mediators by
      osteoblasts. According to these in vitro results, it seems rather plausible that
      alumina particles are able to initiate an inflammatory response in vivo.

PMID- 16419969
TI  - Role of free radicals in aseptic loosening of hip arthroplasty.
AB  - Fibrous pseudocapsule around hip implants is an invariable finding at revision
      operations and is believed to release inflammatory mediators that stimulate bone
      resorption. Reactive oxygen species have been proposed to be causative factors in
      various disorders with tissue fibrosis. We were interested in investigating
      whether aseptic loosening is connected with high oxidative stress, and in showing
      the underlying mechanism of periprosthetic fibrosis and its role in loosening.
      Levels of oxidative stress markers reduced (GSH) and oxidized (GSSG) gluthatione
      and malondialdehyde (MDA) were assayed in 28 loose hips and in 12 stable hips
      revised for high rate of wear and osteolysis. Collagen in the periprosthetic
      tissues was measured as hydroxyproline content. Osteolysis and polyethylene wear
      were graded. Increased oxidative stress measured by low GSH/GSSG ratio as well as
      by increased MDA level was established in patients compared to controls.
      Oxidative stress markers intercorrelated significantly. MDA and both GSH and GSSG
      levels correlated significantly with hydroxyproline level. Levels of GSSG and MDA
      were higher in hips with greater polyethylene wear. The results suggest that high
      oxidative stress may play a role in formation of a fibrous membrane observed at
      revision of loose hips. The fibrous pseudocapsule is probably related to high
      intraarticular pressure and expansion of the effective joint space. This study
      may elicit some aspects of the pathogenesis of aseptic hip loosening and aid in
      future investigations aiming at prevention of this complication.

PMID- 16419970
TI  - Collagen degradation products modulate matrix metalloproteinase expression in
      cultured articular chondrocytes.
AB  - Destruction of collagen within osteoarthritic cartilage depends in part on
      collagen-degrading matrix metalloproteases (MMP). Degradative fragments of type
      II collagen (Col II) occur in normal and in osteoarthritic cartilage, and may
      contribute to regulation of matrix turnover by interfering with normal cell
      matrix communication pathways. Therefore, the effects of different types of
      collagen fragments on mRNA and protein levels of MMP-2, MMP-3, MMP-9, and MMP-13
      in cultured bovine articular knee chondrocytes and explants were examined.
      Primary chondrocytes and explants were incubated with fragments from whole
      cartilage collagen matrix (Colf) and from purified type II collagen (Col2f), or
      with a synthetic 29-mer peptide representing the amino-terminal domain of type II
      collagen (Ntelo). Gelatin zymography revealed increases of proMMP-2, a shift
      towards active MMP-2 and increases in proMMP-9, depending on the type of
      fragment. In situ hybridization of cartilage sections displayed MMP-3 mRNA in
      virtually all cells. Moderate to strong increases in MMP-2, MMP-3, MMP-9, and MMP
      13 mRNA levels were detected by quantitative PCR. The results demonstrate
      stimulating effects of collagen fragments on both mRNA and/or protein from MMP 
      2, -3, -9, and -13, and suggest a novel mechanism of MMP induction and activation
      that includes a particular role for N-telo in controlling catabolic pathways of
      matrix turnover.

PMID- 16419971
TI  - Effect of GDF-5 on ligament healing.
AB  - The effects of growth and differentiation factor-5 (GDF-5) on ligament healing
      were studied using a gap injury model of the medial collateral ligament in rat
      knee joints. The administration of GDF-5 once at the time of surgery
      significantly improved the mechanical properties of the femur-ligament-tibia
      complex. At 3 weeks after surgery, 30 microg of GDF-5 improved the ultimate
      tensile strength of the complex by 41%, and the stiffness by 60%, compared with
      the vehicle control (p < 0.05 for both; Fisher's PLSD test). The observation with
      a transmission electron microscopy revealed that GDF-5 increased the diameter of
      collagen fibrils in the repair tissue, which was considered to be a possible
      mechanism for the positive result in the biomechanical testing. Quantitative PCR
      and in situ hybridization revealed enhanced type I procollagen expression by GDF
      5, and the PCR analysis also revealed that the GDF-5 treatment reduced the
      expression of type III procollagen relative to type I procollagen. The PCR
      analysis further showed that the expression of decorin and fibromodulin was
      relatively reduced against type I procollagen by the growth factor, which was
      considered to be responsible for the increase of collagen fibril diameter in the
      repair tissue. No adverse effects were observed, and the use of GDF-5 was
      considered a promising approach to facilitate ligament healing.

PMID- 16419972
TI  - Overexpression of nitric oxide synthases in tendon overuse.
AB  - Tendon disorders with a chronic nature, including the rotator cuff, are extremely
      common, and represent a major clinical problem. Mechanical overload has been
      proposed as an important etiologic factor in tendinopathies. Nitric oxide (NO), a
      free radical produced by nitric oxide synthases (NOSs), is a potent regulator and
      stimulator of biological processes including tendon degeneration and healing. It
      is also involved in response to mechanical stimuli in different tissues. In an
      animal model of acutely injured tendon healing temporal and differential
      expression of NOS isoforms has been demonstrated, suggesting that different
      patterns of NOSs expression may have different biological functions. Therefore,
      we hypothesized that tendon overuse may result in a differential upregulation of
      NOSs, particularly iNOS. An animal model of supraspinatus tendon overuse was
      utilized, which consisted of treadmill running. A group of animals of the same
      strain and age subjected to normal cage activity were used as controls. Following
      a 4-week exercise protocol supraspinatus tendons were harvested, RNA was
      extracted, and subjected to competitive reverse transcription and polymerase
      chain reaction (RT-PCR) to determine the expression levels of inducible-,
      endothelial-, and neuronal-NOS isoforms (i-, e-, and nNOS). The mRNA expression
      of all three NOS isoforms increased in the supraspinatus tendons as a result of
      overuse exercise. iNOS and eNOS mRNA expression increased fourfold (p < 0.01),
      and there was an increase, but statistically not significant, in nNOS mRNA
      expression in the overused tendons when compared with the controls. This study is
      the first to show that NOS isoforms are upregulated in rotator cuff tendon as a
      result of chronic overuse, and suggests the involvement of nitric oxide in the
      response of tendon tissue to increased mechanical stress.

PMID- 16419973
TI  - Intracellular Staphylococcus aureus and antibiotic resistance: implications for
      treatment of staphylococcal osteomyelitis.
AB  - Staphylococcus aureus is responsible for 80% of human osteomyelitis. It can
      invade and persist within osteoblasts. Antibiotic resistant strains of S. aureus
      make successful treatment of osteomyelitis difficult. NULL HYPOTHESIS: antibiotic
      sensitivities of S. aureus do not change after exposure to the osteoblast
      intracellular environment. Human and mouse osteoblast cultures were infected and
      S. aureus cells were allowed to invade. Following times 0, 12, 24, and 48 h ( +/-
      the addition of erythromycin, clindamycin, and rifampin at times 0 or 12 h), the
      osteoblasts were lysed and intracellular bacteria enumerated. Transmission
      electron microscopy was performed on extracellular and intracellular S. aureus
      cells. In mouse osteoblasts, administration of bacteriostatic antibiotics at time
      0 prevented the increase in intracellular S. aureus. If the antibiotics were
      delayed 12 h, this did not occur. When rifampin (bactericidal) was introduced at
      time 0 to human and mouse osteoblasts, there was a significant decrease in number
      of intracellular S. aureus within osteoblasts compared to control. If rifampin
      was delayed 12 h, this did not occur. Significant time-dependent S. aureus
      structural changes were observed after exposure to the osteoblast intracellular
      environment. These studies demonstrate that once S. aureus is established
      intracellularly for 12 h, the bacteria are less sensitive to antibiotics capable
      of eukaryotic cell penetration (statistically significant). These antibiotic
      sensitivity changes could be due in part to the observed structural changes. This
      leads to the rejection of our null hypotheses that the antibiotic sensitivities
      of S. aureus are unaltered by their location.

PMID- 16419974
TI  - HLA-restricted specific tumor cytolysis by autologous T-lymphocytes infiltrating
      metastatic bone malignant fibrous histiocytoma of lymph node.
AB  - Malignant fibrous histiocytoma (MFH) of the bone is a high-grade sarcoma
      characterized histologically by the composition of fibroblasts and pleomorphic
      cells with a prominent storiform pattern. Despite institution of multi-modality
      treatments, the prognosis for patients with this tumor remains unsatisfactory. In
      the present study, towards the goal of developing active immunotherapy for those
      affected, we established four cell lines from a 53-year-old woman who suffered
      from MFH of the humerus with lymph node metastases. MFH2003 and MFH2003-B7.1 were
      the primary lesion-derived cell line and its B7.1-transfectant, respectively.
      B2003-EBV and TIL2003 were a B cell line established from peripheral blood
      lymphocytes and a T cell line established from tumor-invaded lymph nodes,
      respectively. MFH2003 cells could be maintained over a period of 1 year in vitro,
      and could be xenotransplanted into nude mice. The phenotype of cells analyzed by
      immunostaining was similar to the original tumor. TIL2003 cells were all CD8+ and
      specifically recognized MFH2003 cells and MFH2003-B7.1 cells, but not B2003-EBV
      cells. An anti-HLA-class I monoclonal antibody completely blocked the anti
      MFH2003 response of TILs2003. These findings indicate the existence of an anti
      MFH specific immune response in the microenvironment of metastatic lymph nodes.
      The present autologous cell lines provide the basis for identification of novel
      tumor-associated antigens and may be helpful in the establishment of
      immunotherapy for patients with MFH of the bone.

PMID- 16419976
TI  - Re: Shoulder prostheses treating cuff tear arthropathy: a comparative
      biomechanical study.

PMID- 16419975
TI  - The cut intramuscular nerve affects the recovery in the lacerated skeletal
      muscle.
AB  - The recovery of lacerated skeletal muscles are said to be slow and incomplete.
      Often the intramuscular (IM-) nerve is concomitantly cut, but never repaired. We
      questioned whether the IM-nerve should also be reanastamosed before repairing the
      skeletal muscle. Before answering this, it was necessary to know if the cut IM
      nerve would have an effect on the recovery of the segment of muscle distal to the
      level of the laceration. This study investigates the recovery of lacerated
      muscles after repair, and compares a complete muscle laceration where the main IM
      nerve was concomitantly cut and an incomplete muscle laceration where the IM
      nerve was preserved intact. The medial gastrocnemius (MG) of the adult male New
      Zealand White rabbit was used, with the contralateral muscle as a sham control.
      The laceration was at the proximal quarter of the muscle, distal to the entry
      point of the nerve branch from the tibial nerve into the muscle belly. Twenty
      eight weeks post-repair, the lacerated MG with the IM-nerve intact showed
      improved muscle wet weight, near normal morphology and contractile properties,
      and return of muscle fiber type mix and size. The repaired lacerated MG with
      their IM-nerve concomitantly cut demonstrated loss of muscle wet weight, obvious
      fibrosis, mononuclear proliferation with fatty infiltration, increase in type-1
      fibers and muscle fiber atrophy in the distal portion. We postulate that it might
      be important to repair the intramuscular nerve branch by microanastomosis when
      repairing a vital skeletal muscle that is lacerated.

PMID- 16419977
TI  - Recurrent or refractory trigeminal neuralgia after microvascular decompression,
      radiofrequency ablation, or radiosurgery.
AB  - OBJECT: Trigeminal neuralgia (TN) is characterized by paroxysmal lancinating pain
      in the trigeminal nerve distribution. When TN is refractory to medical
      management, patients are referred for microvascular decompression (MVD),
      radiofrequency ablation, or radiosurgery. After the initial treatment, patients
      may have refractory or recurrent symptoms requiring retreatment. The purpose of
      this study was to determine what factors are associated with the need for
      retreatment and which modality is most effective. METHODS: To define this
      population further, the authors evaluated a cohort of patients who required
      retreatment for TN. The mean follow-up periods were 51 months from the first
      treatment and 23 months from the last one, and these were comparable among
      treatment groups. CONCLUSIONS: Trigeminal neuralgia can recur after neurosurgical
      treatment. In this study the authors demonstrate that the number of patients
      requiring retreatment is not negligible. Lower retreatment rates were seen in
      patients who initially underwent radiosurgery, compared with those in whom MVD or
      radiofrequency ablation were performed. Radiosurgery was more likely to be the
      final treatment for recurrent TN regardless of the initial treatment. After
      retreatment, the majority of patients attained complete or very good pain relief.
      Pain relief after retreatment correlates with postoperative facial numbness.

PMID- 16419979
TI  - Relations between transport coefficients and their density and temperature
      dependence.
AB  - Nonequilibrium statistical mechanics via density fluctuation theory predicts
      relations between the bulk and shear viscosity, thermal conductivity, and self
      diffusion coefficient of a fluid. In this Feature Article, we discuss such
      relations holding for fluids over wide ranges of density and temperature
      experimentally studied in the laboratory. It is discussed how such relations can
      be used to successfully compute the density and temperature dependence on the
      basis of intermolecular interaction potential models with the help of the
      modified free volume theory and the generic van der Waals equation of state once
      the parameters in them are determined at a low density or at a subcritical
      temperature. Although some approximations have been made to derive them, they
      represent a reliable molecular theory of transport coefficients over the entire
      density and temperature ranges of fluids--namely, gases and liquids--a theory
      hitherto unavailable in the kinetic theory of liquids and dense gases.

PMID- 16419978
TI  - Management of medically refractory trigeminal neuralgia in patients with multiple
      sclerosis.
AB  - OBJECT: Trigeminal neuralgia (TN) is a painful disorder that frequently causes
      lancinating, electrical shock-like pain in the trigeminal distribution. Common
      surgical treatments include microvascular decompression (MVD), radiosurgery, and
      radiofrequency ablation, and complete pain relief is generally achieved with a
      single treatment in 70 to 85% of cases for all modalities. In a subset of
      patients with multiple sclerosis (MS), however, the rates of surgical treatment
      failure and the need for additional procedures are significantly increased
      compared with those in patients without MS. In this study the authors report
      their experience with a cohort of 11 patients with TN who also had MS, and assess
      the efficacy of MVD, gamma knife surgery (GKS), and radiofrequency ablation in
      achieving complete or partial long-term pain relief. METHODS: Eleven patients
      with TN and MS who were treated by the senior author (N.B.) at the University of
      California, San Francisco were included in this study. All patients underwent GKS
      and/or radiofrequency ablation, and four received MVD. A detailed clinical
      history and intraoperative findings were recorded for each patient and frequent
      follow-up evaluations were performed, with a mean follow-up duration of 40.6
      months (range 1-96 months). Pain was assessed for each patient by using the
      Barrow Neurological Institute scale (Scores I-V). CONCLUSIONS: Achieving complete
      pain relief in patients with TN and MS required significantly more treatments
      compared with all other patients with TN who did not have MS (p = 0.004). Even
      when compared with a group of 32 patients who had highly refractory TN, the
      cohort with MS required significantly more treatments (p = 0.05). Radiosurgery
      proved to be an effective procedure and resulted in fewer retreatments and longer
      pain-free intervals compared with MVD or radiofrequency ablation.

PMID- 16419980
TI  - Photodissociation of propargyl chloride at 193 nm.
AB  - The photodissociation of propargyl chloride (C3H3Cl) has been studied at 193 nm.
      Ion imaging experiments with state-selective detection of the Cl atoms and single
      photon ionization of the C3H3 radicals were performed, along with measurements of
      the Cl + C3H3 and HCl + C3H2 recoil kinetic energy distributions, using a
      scattering apparatus with electron bombardment ionization detection to resolve
      the competing Cl and HCl elimination channels. The experiments allow the
      determination of the Cl (2P3/2) and Cl (2P1/2) (hereafter Cl) branching fractions
      associated with the C-Cl bond fission, which are determined to be 0.5 +/- 0.1 for
      both channels. Although prior translational spectroscopy studies by others had
      concluded that the low velocity signal at the Cl+ mass was due to daughter
      fragments of the HCl elimination products, the present work shows that Cl atoms
      are produced with a bimodal recoil kinetic energy distribution. The major C-Cl
      bond fission channel, with a narrow recoil kinetic energy distribution peaking
      near 40 kcal/mol, produces both Cl and Cl, whereas the minor (5%) channel,
      partitioning much less energy to relative kinetic energy, produces only ground
      spin-orbit state Cl atoms. The maximum internal energy of the radicals produced
      in the low-recoil-kinetic-energy channel is consistent with this channel
      producing electronically excited propargyl radicals. Finally, in contrast to
      previous studies, the present work determines the HCl recoil kinetic energy
      distribution and identifies the possible contribution to this spectrum from
      propargyl radicals cracking to C3+ ions in the mass spectrometer.

PMID- 16419981
TI  - Resonance Raman investigation of the short-time photodissociation dynamics of the
      charge-transfer absorption of the I2-benzene complex in benzene solution.
AB  - Resonance Raman spectra were obtained for the I2-benzene complex in benzene
      solvent with excitation wavelengths in resonance with the CT-band absorption.
      These spectra indicate that the Franck-Condon region photodissociation dynamics
      have multidimensional character with motion mainly along the nominal I-I stretch
      mode nu(18), the nominal symmetric benzene ring stretch mode nu5, and the nominal
      symmetric CCH bending nu7. There is also a small contribution from the nominal
      out-of-plane CH oop wag nu15. A preliminary resonance Raman intensity analysis
      was done, and the results for the I2-benzene complex were compared to results
      previously reported for the 1-hexene-I2 complex. We briefly discuss the
      differences and similarities in the CT-band absorption excitation of an I2
      benzene complex relative to those of an I2-alkene complex.

PMID- 16419982
TI  - Effect of solvation on pinched cone-pinched cone interconversion of
      tetraethoxycalix[4]arene and tetraethoxythiacalix[4]arene.
AB  - The pinched cone-pinched cone interconversion (PCI) of tetraethoxy substituted
      calix[4]arene and thiacalix[4]arene was studied by means of molecular dynamics
      using the GAFF force field and quantum mechanics. Influence of solvent was
      expressed by changes in cavity geometries as well as in free energy barriers that
      were calculated using constrained MD simulations. Water and chloroform were found
      to reduce the energy barriers in comparison with vacuum simulations. Only
      qualitative agreement between energy barriers calculated by MD and experimental
      values was achieved. Also, quantum chemical calculations were performed with the
      RI-MP2 method, and a better description of PCI was achieved than that previously
      obtained by HF or DFT methods. The combination of qualitative MD data on solvated
      systems with RI-MP2 gas-phase data gave us very good agreement with experimental
      results.

PMID- 16419983
TI  - 13C NMR relaxation rates in the ionic liquid 1-ethyl-3-methylimidazolium
      butanesulfonate.
AB  - A new method of obtaining molecular reorientational dynamics from 13C spin
      lattice relaxation data of aromatic carbons in viscous solutions is applied to
      13C relaxation data of both the cation and anion in the ionic liquid, 1-ethyl-3
      methylimidazolium butanesulfonate ([EMIM]BSO3). 13C pseudorotational correlation
      times are used to calculate corrected maximum NOE factors from a combined
      isotropic dipolar and nuclear Overhauser effect (NOE) equation. These corrected
      maximum NOE factors are then used to determine the dipolar relaxation rate part
      of the total relaxation rate for each aromatic 13C nucleus in the imidazolium
      ring. Rotational correlation times are compared with viscosity data and indicate
      several [EMIM]BSO3 phase changes over the temperature range from 278 to 328 K.
      Modifications of the Stokes-Einstein-Debye (SED) model are used to determine
      molecular radii for the 1-ethyl-3-methylimidazolium cation. The Hu-Zwanzig
      correction yields a cationic radius that compares favorably with a DFT gas-phase
      calculation, B3LYP/(6-311+G(2d,p)). Chemical shift anisotropy values, Deltasigma,
      are obtained for the ring and immediately adjacent methylene and methyl carbons
      in the imidazolium cation and for the three carbon atoms nearest to the sulfonate
      group in the anion.

PMID- 16419984
TI  - Evidence of site-specific fragmentation on thioacetic acid, CH3C(O)SH, irradiated
      with synchrotron radiation around the S 2p and O 1s regions.
AB  - Site-specific fragmentations following S 2p and O 1s photoexcitation of
      thioacetic acid, CH3C(O)SH, have been studied by means of synchrotron radiation.
      Total ion yield (TIY) spectra were measured and multicoincidence techniques,
      which include photoelectron-photoion coincidence (PEPICO) and photoelectron
      photoion-photoion coincidence (PEPIPICO) time-of-flight mass spectrometry, were
      applied. The equivalent-core approximation was employed in order to estimate
      ionization transition values, and the observed peaks were tentatively assigned. A
      site-specific fragmentation is moderately observed by comparing the mass spectra
      collected at resonant energies around the inner and shallow inner shell S 2p and
      O 1s ionization edges. Beside H+ ion, the most abundant ions observed at the S 2p
      edge excitation were CH3CO+, SH+, S+, and CH3+. At the O 1s region the large
      CH3CO+ fragment was depressed, and small CHx+ (x = 0, 1, 2, 3), S+, and SH+
      fragments were dominant. The dissociation dynamic for the main ion-pair
      production has been discussed. Two- and three-body dissociation channels have
      been observed in the PEPIPICO spectra, and the dissociation mechanisms were
      proposed.

PMID- 16419985
TI  - Photoinduced processes in a tricomponent molecule consisting of
      diphenylaminofluorene-dicyanoethylene-methano[60]fullerene.
AB  - Photoinduced intramolecular processes in a tricomponent molecule C60(>(CN)2
      DPAF), consisting of an electron-accepting methano[60]fullerene moiety (C60>)
      covalently bound to an electron-donating diphenylaminofluorene (DPAF) unit via a
      bridging dicyanoethylenyl group [(CN)2], were investigated in comparison with
      (CN)2-DPAF. On the basis of the molecular orbital calculations, the lowest charge
      separated state of C60(>(CN)2-DPAF) is suggested to be C60*-(>(CN)2-DPAF*+) with
      the negative charge localized on the fullerene cage, while the upper state is
      C60(>(CN)2*--DPAF*+). The excited-state events of C60(>(CN)2-DPAF) were monitored
      by both time-resolved emission and nanosecond transient absorption techniques. In
      both nonpolar and polar solvents, the excited charge-transfer state decayed
      mainly through initial energy-transfer process to the C60 moiety yielding the
      corresponding 1C60, from which charge separation took place leading to the
      formation of C60*-(>(CN)2-DPAF*+) in a fast rate and high efficiency. In
      addition, multistep charge separation from C60(>(CN)2*--DPAF*+) to C60*-(>(CN)2
      DPAF*+) may be possible with the excitation of charge-transfer band. The
      lifetimes of C60*-(>(CN)2-DPAF*+) are longer than the previously reported
      methano[60]fullerene-diphenylaminofluorene C60(>(C=O)-DPAF) with the C60 and DPAF
      moieties linked by a methanoketo group. These findings suggest an important role
      of dicyanoethylenyl group as an electron mediating bridge in C60(>(CN)2-DPAF).

PMID- 16419986
TI  - Matrix isolation investigation of the photochemical reaction of methyl
      substituted benzenes with CrCl2O2.
AB  - The matrix isolation technique, combined with infrared spectroscopy, has been
      used to characterize the products of the photochemical reactions of toluene, m-,
      o-, and p-xylene, mesitylene, and hexamethylbenzene with CrCl2O2. While initial
      twin jet deposition of the reagents led to no visible changes in the recorded
      spectra, strong product bands were noted following irradiation with light of
      lambda > 300 nm. The irradiation was shown to lead to oxygen atom transfer,
      forming complexes between methylcyclohexadienone derivatives and CrCl2O. With the
      xylenes and mesitylene, di- and trimethylphenols, complexed to CrCl2O, were also
      observed, respectively. This latter result arises from C-H bond activation and
      oxygen atom insertion into a C-H bond. The identification of the complexes was
      further supported by isotopic labeling (2H) and by density functional
      calculations at the B3LYP/6-311G++(d,2p) level. Product distributions were
      rationalized by an analysis of the electron density distribution.

PMID- 16419987
TI  - Matrix isolation study of the reactions of CrO2Cl2 with a series of silanes.
AB  - The reactions between CrO2Cl2 and a series of silanes have been investigated
      using matrix isolation infrared spectroscopy. Twin-jet codeposition of the two
      reagents into argon matrices at 14 K followed by irradiation with light of lambda
      > 300 nm led to the growth of a number of new bands. These have been assigned to
      the appropriate silanol species formed by oxygen insertion into the Si-H bond,
      strongly complexed to CrCl2O. The structures and vibrational frequencies of these
      complexes have been characterized by high-level theoretical calculations. These
      calculations also support the relative preference for the insertion reaction
      compared to other possible pathways. Merged-jet codeposition of SiH2Cl2 with
      CrO2Cl2 at 200 degrees C also led to the formation of the free silanol, HSiCl2OH.

PMID- 16419988
TI  - Structural evolution of anionic silicon clusters SiN (20 <or= N <or= 45).
AB  - Results of a combined photoelectron spectroscopy and first-principles density
      functional study of SiN- clusters in the size range 20 <or= N <or= 45 are
      reported and discussed. Evidence for a prolate-to-near-spherical shape transition
      at N = 27 is presented. It is shown that the tricapped-trigonal-prism (TTP)
      structural motif Si9 found in most low-lying clusters SiN-, 9 <or= N <or= 19, is
      replaced or augmented by a series of structural motifs consisting of a bulklike
      "adamantane" fragment plus a magic-number cluster (Si6, Si7, Si10) or TTP Si9 in
      low-lying prolate clusters SiN-, N >or= 20. For 28 <or= N <or= 45, almost all low
      lying near-spherical clusters SiN- adopt "stuffed-cage"-like structures where the
      cages are homologous to carbon fullerenes in the sense that they are composed of
      only five- and six-membered rings. However the arrangement of the "stuffing"
      atoms is not yet diamondlike.

PMID- 16419989
TI  - CH-stretching overtone spectra of cis- and trans-1,3-pentadiene.
AB  - The room-temperature vapor-phase overtone spectra of cis- and trans-1,3
      pentadiene (piperylene) have been recorded in the 5000-17500 cm(-1) region with
      the use of conventional and intracavity laser photoacoustic spectroscopy. The
      presence of five nonequivalent olefinic CH bonds and one methyl group in each
      molecule complicates assignment of the spectra. We have used a harmonically
      coupled anharmonic oscillator local mode model with one oscillator for each of
      the nonequivalent CH bonds to calculate the CH-stretching overtone spectra and
      thus facilitate assignment of the spectra. Our calculated spectra are in good
      agreement with the observed spectra. The observed high overtone spectra are
      distinctively different despite the similarity of the two molecules and the
      numerous and broad transitions.

PMID- 16419990
TI  - Conformational composition of cyclopentadienylphosphine investigated by microwave
      spectroscopy and quantum chemical calculations.
AB  - The properties of cyclopentadienylphosphine have been investigated by means of
      Stark-modulation microwave spectroscopy and quantum chemical calculations at the
      MP2/aug-cc-pVTZ, B3LYP/6-311++G(d,p), and G3 levels of theory. Spectra
      attributable to two rotamers denoted conformers I and II have been assigned.
      Conformer I has a symmetry plane (Cs symmetry) consisting of the bisectors of the
      cyclopentadiene ring and of the phosphino group with the lone electron pair of
      phosphorus pointing toward the carbon ring. In conformer II, the phosphino group
      is rotated approximately 120 degrees out of this plane. Relative intensity
      measurements have been made, and it was found that conformer II is more stable
      than I by 1.3(4) kJ/mol. The preferred conformer represents a borderline case of
      intramolecular hydrogen bond stabilization. The experimental and MP2/ aug-cc-pVTZ
      rotational constants differ by several percent, which indicates that the aug-cc
      pVTZ basis set is not large enough to be able to predict an accurate structure
      for the two conformers that are close to the equilibrium geometries. 5
      Substituted 1,3-cyclopentadienyl derivatives may undergo circumambulatory
      rearrangements. However, there is no manifestation of this effect in the
      microwave spectrum of cyclopentadienylphosphine.

PMID- 16419991
TI  - Kinetic energy of free electrons affects MALDI positive ion yield via capture
      cross-section.
AB  - A method for enhancing positive analyte ion signal in MALDI is described. The
      idea is based on influencing the kinetic energy of free electrons emitted from
      the organic/metal interface. It has been recently shown that free electrons in
      MALDI have energies around 1 eV. This energy is close to the maximum capture
      cross-section of most common MALDI matrices, leading to the efficient formation
      of negative matrix ions. This results in the reduction of the positive analyte
      ion yield. The effect can be minimized by shifting the kinetic energy of the
      electrons away from the maximum of the matrix capture cross-section by choosing a
      different substrate material.

PMID- 16419992
TI  - Photogeneration of distant radical pairs in aqueous pyruvic acid glasses.
AB  - The lambda > 300 nm photolysis of h4- or d4-pyruvic acid aqueous glasses at 77 K
      yields identical electron magnetic resonance (EMR) spectra arising from distant
      (r greater or similar 0.5 nm) triplet radical pairs. Spectra comprise: (1) well
      resolved quartets, X, at g approximately ge, that closely match the powder
      spectra of spin pairs interacting across r approximately 1.0 nm with D
      approximately 3.0 mT, E approximately 0 mT zero field splittings (ZFS), and (2)
      broad signals, Y, centered at g approximately 2.07 that display marked g
      anisotropy and g-strain, exclude D greater or similar 20.0 mT values (i.e., r
      less or similar 0.5 spin nm separations), and track the temperature dependence of
      related g approximately 4 features. These results imply that the n-pi excitation
      of pyruvic acid, PA, induces long-range electron transfer from the promoted
      carbonyl chromophore into neighboring carbonyl acceptors, rather than homolysis
      into contact radical pairs or concerted decarboxylation into a carbene. Since PA
      is associated into hydrogen-bonded dimers prior to vitrification, X signals arise
      from radical pairs ensuing intradimer electron transfer to a locked acceptor,
      while Y signals involve carbonyl groups attached to randomly arranged, disjoint
      monomers. The ultrafast decarboxylation of primary radical ion pairs, 3[PA+* PA
      *], accounts for the release of CO2 under cryogenic conditions, the lack of
      thermal hysteresis displayed by magnetic signals between 10 and 160 K, and
      averted charge retrotransfer. All EMR signals disappear irreversibly above the
      onset of ice diffusivity at approximately 190 K.

PMID- 16419993
TI  - Kinetics of the gas-phase reaction of OH with HCl.
AB  - The reaction of hydroxyl radicals with hydrogen chloride (reaction 1) has been
      studied experimentally using a pulsed-laser photolysis/pulsed-laser-induced
      fluorescence technique over a wide range of temperatures, 298-1015 K, and at
      pressures between 5.33 and 26.48 kPa. The bimolecular rate coefficient data set
      obtained for reaction 1 demonstrates no dependence on pressure and exhibits
      positive temperature dependence that can be represented with modified three
      parameter Arrhenius expression within the experimental temperature range: k1 =
      3.20 x 10(-15)T0.99 exp(-62 K/T) cm3 molecule(-1) s(-1). The potential-energy
      surface has been studied using quantum chemical methods, and a transition-state
      theory model has been developed for the reaction 1 on the basis of calculations
      and experimental data. The model results in modified three-parameter Arrhenius
      expressions: k1 = 8.81 x 10(-16)T1.16 exp(58 K/T) cm3 molecule(-1) s(-1) for the
      temperature range 200-1015 K and k1 = 6.84 x 10(-19)T2.12 exp(646 K/T) cm3
      molecule(-1) s(-1) for the temperature dependence of the reaction 1 rate
      coefficient extrapolation to high temperatures (500-3000 K). A temperature
      dependence of the rate coefficient of the Cl + H2O --> HCl + OH reaction has been
      derived on the basis of the experimental data, modeling, and thermochemical
      information.

PMID- 16419994
TI  - Insights into photodissociation dynamics of propionyl chloride from ab initio
      calculations and molecular dynamics simulations.
AB  - The potential energy surfaces of isomerization, dissociation, and elimination
      reactions for CH3CH2COCl in the S0 and S1 states have been mapped with the
      different ab initio calculations. Mechanistic photodissociation of CH3CH2COCl at
      266 nm has been characterized through the computed potential energy surfaces, the
      optimized surface crossing structure, intrinsic reaction coordinate, and ab
      initio molecular dynamics calculations. Photoexcitation at 266 nm leads to the
      CH3CH2COCl molecules in the S1 state. From this state, the C-Cl bond cleavage
      proceeds in a time scale of picosecond in the gas phase. The barrier to the C-Cl
      bond cleavage on the S1 surface is significantly increased by effects of the
      matrix and the internal conversion to the ground state prevails in the condensed
      phase. The HCl eliminations as a result of internal conversion to the ground
      state become the dominant channel upon photodissociation of CH3CH2COCl in the
      argon matrix at 10 K.

PMID- 16419995
TI  - Magnesium sulfate aerosols studied by FTIR spectroscopy: hygroscopic properties,
      supersaturated structures, and implications for seawater aerosols.
AB  - Supersaturated MgSO4 aerosols and dilute MgSO4 solutions were studied by FTIR
      spectroscopic techniques (i.e., aerosol flow tube (AFT) and attenuated total
      reflection (ATR)). The hygroscopic properties of MgSO4 aerosols were investigated
      with results in good agreement with previous measurements by a scanning
      electrodynamic balance (SEDB). Well-defined spectral evolutions with changing
      relative humidity (RH) for the v3 band of SO4(2-) and the water O-H stretching
      envelope could be directly related to the observed hygroscopic properties of
      MgSO4 aerosols. When the RH decreased from approximately 55 to approximately 40%,
      the v1 band of SO4(2-) in supersaturated MgSO4 aerosols was observed to transform
      from a sharp peak at approximately 983 cm(-1) into a wide band at approximately
      1005 cm(-1). The sharp peak at approximately 983 cm(-1) was mainly assigned to
      such associated complexes of Mg2+ and SO4(2-) as double solvent-separated ion
      pairs (2SIPs), solvent-shared ion pairs (SIPs), and simple contact ion pairs
      (CIPs) in supersaturated MgSO4 aerosols, while the wide band at approximately
      1005 cm(-1) was due to polymeric CIPs chains, probably the main component of gels
      formed in MgSO4 aerosols at low RHs. Relating to this v1 band transformation, the
      peak position of the v(3) band was first shown to be a sensitive indicator of
      CIPs formation, spanning across approximately 40 cm(-1) on the formation of
      polymeric CIPs chains, which could also be supported by aerosol composition
      analysis in the form of water-to-solute molar ratios (WSR). In the water O-H
      stretching envelope, the absorbance intensities at 3371 and 3251 cm(-1) were
      selected to represent contributions from weak and strong hydrogen bonds,
      respectively. The absorbance intensity ratio changing with RH of 3371 to 3251 cm(
      1) could be related to the previous observations with the v1 and v3 bands of
      SO4(2-). As a result, the formation of CIPs with various structures in large
      amounts was supposed to significantly weaken hydrogen bonds in supersaturated
      MgSO4 aerosols, while 2SIPs and SIPs were not expected to have similar effects
      even when occurring in abundance. In comparison with MgSO4 aerosols, the peak
      positions of the v3 band of SO4(2-) in artificial seawater aerosols implied that
      the MgSO4 component should be contained as gels or concentrated solutions in the
      fissures of microcrystals of sea salts for freshly formed seawater aerosols at
      low RHs.

PMID- 16419996
TI  - Gas-phase uranyl-nitrile complex ions.
AB  - Electrospray ionization was used to generate doubly charged complex ions composed
      of the uranyl ion and nitrile ligands. The complexes, with general formula
      [UO2(RCN)n]2+, n = 0-5 (where R=CH3-, CH3CH2-, or C6H5-), were isolated in an ion
      trap mass spectrometer to probe intrinsic reactions with H2O. For these
      complexes, two general reaction pathways were observed: (a) the direct addition
      of one or more H2O ligands to the doubly charged complexes and (b) charge
      reduction reactions. For the latter, the reactions produced uranyl hydroxide,
      [UO2OH], complexes via collisions with gas-phase H2O molecules and the
      elimination of protonated nitrile ligands.

PMID- 16419997
TI  - Global dynamic optimization for parameter estimation in chemical kinetics.
AB  - We present the first method guaranteed to find the best possible least-squares
      (chi2) fit of experimental data by a nonlinear kinetic model. Several important
      advantages of knowing with certainty the best possible fit rather than a locally
      optimum fit are discussed and demonstrated using data from the recent literature.
      This is particularly important when the model and the data appear to be
      inconsistent. With the new method, one can rigorously demonstrate that a
      nonlinear kinetic model with several adjustable rate parameters is inconsistent
      with measured experimental data. The numerical method presented is a valuable
      tool in evaluating the validity of a complex kinetics model.

PMID- 16419998
TI  - Determination of the rate constant for the radical-radical reaction NCO(X2Pi) +
      CH3(X2A2 '') at 293 K and an estimate of possible product channels.
AB  - The rate constant for the reaction of the cyanato radical, NCO(X2Pi), with the
      methyl radical, CH3(X2A2' '), has been measured to be (2.1 +/- 1.3(-0.80)) x 10(
      10) cm3 molecule(-1) s(-1), where the uncertainty includes both random and
      systematic errors at the 68% confidence level. The measurements were conducted
      over a pressure range of 2.8-4.3 Torr of CH4 and at a temperature of 293 +/- 2 K.
      The radicals were generated by the 248-nm photolysis of ClNCO in a large excess
      of CH4. The subsequent rapid reaction, Cl + CH4, generated the CH3 radical. The
      rate constant for the Cl + CH4 reaction was measured to be (9.2 +/- 0.2) x 10(
      14) cm3 molecule(-1) s(-1), where the uncertainty is the scatter of one standard
      deviation in the data. The progress of the reaction was followed by time-resolved
      infrared absorption spectroscopy on single rovibrational transitions from the
      ground vibrational level. Multiple species were detected in these experiments,
      including NCO, CH3, HCl, C2H6, HCN, HNC, NH, and HNCO. Temporal concentration
      profiles of the observed species were simulated using a kinetic model, and rate
      constants were determined by minimizing the sum of the squares of the residuals
      between experimental observations and model calculations. Both HCN and HNC seem
      to be minor products (<0.3% each) of the NCO + CH3 reaction. The peak
      concentrations of NH and HNCO were small, accounting for <1% of the initial NCO
      concentration; however, their temporal profiles could not be fit by the model
      kinetics. The observed C2H6 temporal profile always peaked at significantly
      higher concentrations than the model predictions, and several reaction models
      were constructed to help explain these observations. The most likely product
      channel seems to be the recombination channels, producing CH3NCO and CH3OCN.

PMID- 16419999
TI  - Uncatalyzed reactions in the classical Belousov-Zhabotinsky system. 2. The
      malonic acid-bromate reaction in acidic media.
AB  - The title reaction was studied with various techniques in 1 M sulfuric acid, a
      usual medium for the oscillatory Belousov-Zhabotinsky (BZ) reaction. It was found
      to be a more complex process than the bromomalonic acid (BrMA)-BrO3- reaction
      studied previously in the first part of this work. Malonic acid (MA) can react
      with acidic bromate by two parallel mechanisms. The main aim of the present
      research was to determine the mechanisms, the rate laws, and the rate constants
      for these parallel channels. In one reaction channel the first molecular products
      are glyoxalic acid (GOA) and CO2 while in the other channel mesoxalic acid (MOA)
      is the first molecular intermediate, that is, no CO2 is formed in this step. To
      prove these two independent routes specific colorimetric techniques were
      developed to determine GOA and MOA selectively. The rate of the GOA channel was
      determined by following the rate of the carbon dioxide evolution characteristic
      for this reaction route. In this step, regarding it as an overall process, one MA
      is oxidized to GOA and CO2 and one BrO3- is reduced to HOBr, which forms BrMA
      with another MA. The initial rate of the GOA channel is a bilinear function of
      the initial MA and BrO3- concentrations with a second-order rate constant k(GOA)=
      2.4 x 10(-7) M(-1) s(-1). The rate of the other channel was calculated from the
      rate of the BrO3- consumption measured in separate experiments, assuming that the
      measured depletion is a sum of two separate terms reflecting the consumptions due
      to the two independent channels. In the MOA channel one MA is oxidized to MOA and
      one BrO3- is consumed while another MA is brominated as in the GOA channel. It
      was found that the initial rate of the MOA channel is also a bilinear function of
      the MA and BrO3- concentrations with a second-order rate constant k(MOA)= 2.46 x
      10(-6) M(-1) s(-1). Separate chemical mechanisms are suggested for both channels.
      In all of the various bromate-substrate reactions of these mechanisms oxygen atom
      transfer from the bromate to the substrate occurs generating bromous acid
      intermediate. This can be of high importance in BZ systems as bromous acid is the
      autocatalytic intermediate there. GOA and MOA also can be oxidized by acidic
      bromate but a study of these reactions will be published later.

PMID- 16420000
TI  - Structures, electron affinities, and harmonic vibrational frequencies of
      C6H5X/C6H5X- (X = N, S, NH, PH, CH2, and SiH2).
AB  - The molecular structures and electron affinities of the C6H5X/C6H5X- (X = N, S,
      NH, PH, CH2, and SiH2) species have been determined using seven different density
      functional or hybrid Hartree-Fock density functional methods. The basis set used
      in this work is of double-zeta plus polarization quality with additional diffuse
      s- and p-type functions, denoted DZP++. These methods have been carefully
      calibrated (Chem. Rev. 2002, 102, 231). The geometries are fully optimized with
      each density functional theory (DFT) method, and discussed. Harmonic vibrational
      frequencies were found to be within 3.2% of available experimental values for
      most functionals. Three different types of the neutral-anion energy separations
      reported in this work are the adiabatic electron affinity (EA(ad)), the vertical
      electron affinity (EA(vert)), and the vertical detachment energy (VDE). The most
      reliable adiabatic electron affinities, obtained at the DZP++ BPW91 level of
      theory, are 1.45 (C6H5N), 2.29 (C6H5S), 1.57 (C6H5NH), 1.51 (C6H5PH), 0.91
      (C6H5CH2), and 1.48 eV (C6H5SiH2), respectively. Compared with the experimental
      values, the average absolute error of the BPW91 method is 0.04 eV. The B3LYP and
      B3PW91 functionals also gave excellent predictions, with average absolute errors
      of 0.06 and 0.07 eV, respectively.

PMID- 16420002
TI  - First hyperpolarizability of a sesquifulvalene transition metal complex by time
      dependent density-functional theory.
AB  - The first hyperpolarizability and electronic excitation spectrum of
      sesquifulvalene and a sesquifulvalene ruthenium complex have been computed and
      analyzed with use of time-dependent density-functional theory. A new orbital
      decomposition scheme is introduced that allows the computed first
      hyperpolarizability to be related to the electronic structure of complex
      molecules. The analysis shows that the first hyperpolarizability of
      sesquifulvalene is not associated with the first intense absorption, with HOMO-1 
      -> LUMO+1 character, but is dominated by the lowest energy transition, with HOMO 
      -> LUMO character, despite its very low intensity. In the ruthenium complex, the
      analysis reveals that the strong enhancement of the nonlinear optical response
      compared to free sesquifulvalene should not be attributed to the effect of
      complexation on the hyperpolarizability of sesquifulvalene. The strong
      hyperpolarizability originates from MLCT transitions from ruthenium d-orbitals to
      an empty orbital located at the seven ring of sesquifulvalene, transitions that
      have no analogue in free sequifulvalene.

PMID- 16420001
TI  - Improved prediction of heats of formation of energetic materials using quantum
      mechanical calculations.
AB  - We present simple atom and group-equivalent methods that will convert quantum
      mechanical energies of molecules to gas phase heats of formation of CHNO systems.
      In addition, we predict heats of sublimation and vaporization derived from
      information obtained from the quantum-mechanically calculated electrostatic
      potential of each isolated molecule. The heats of sublimation and vaporization
      are combined with the aforementioned gas phase heats of formation to produce
      completely predicted condensed phase heats of formation. These semiempirical
      computational methods, calibrated using experimental information, were applied to
      a series of CHNO molecules for which no experimental information was used in the
      development of the methods. These methods improve upon an earlier effort of Rice
      et al. [Rice, B. M.; Pai, S. V.; Hare, J. Combust. Flame 1999, 118, 445] through
      the use of a larger basis set and the application of group equivalents. The root
      mean-square deviation (rms) from experiment for the predicted group-equivalent
      gas phase heats of formation is 3.2 kcal/mol with a maximum deviation of 6.5
      kcal/mol. The rms and maximum deviation of the predicted liquid heats of
      formation are 3.2 and 7.4 kcal/mol, respectively. Finally, the rms and maximum
      deviation of predicted solid heats of formation are 5.6 and 12.2 kcal/mol,
      respectively, an improvement in the rms of approximately 40% compared to the
      earlier Rice et al. predictions using atom equivalents and a smaller basis set
      (B3LYP/6-31G*).

PMID- 16420003
TI  - Theoretical study of the electronic nonadiabatic transitions in the photoelectron
      spectroscopy of F2O.
AB  - The photoelectron spectrum of F2O pertaining to ionizations to the ground (X2B1)
      and low-lying excited electronic states (A2B2, B2A1, and C2A2) of F2O+ is
      investigated theoretically. The near equilibrium potential energy surfaces of the
      ground electronic state (X2B1) of F2O and the mentioned ground and excited
      electronic states of F2O+ reported by Wang et al. ( J. Chem. Phys. 2001, 114,
      10682) for the C2v configuration are extended for the Cs geometry assuming a
      harmonic vibration along the asymmetric stretching mode. The vibronic
      interactions between the A2B2 and B2A1 electronic states of F2O+ are treated
      within a linear coupling approach, and the strength of the vibronic coupling
      parameter is calculated by an ab initio method. The nuclear dynamics is simulated
      by both time-independent quantum mechanical and time-dependent wave packet
      approaches. Although the first photoelectron band exhibits resolved vibrational
      progression along the symmetric stretching mode, the second one is highly
      overlapping. The latter is attributed to the nonadiabatic interactions among the
      energetically close A2B2, B2A1, and C2A2 electronic states of F2O+. The
      theoretical findings are in good accord with the available experimental results.

PMID- 16420004
TI  - On the limits of highest-occupied molecular orbital driven reactions: the
      frontier effective-for-reaction molecular orbital concept.
AB  - We carried out Hartree-Fock (HF) and density functional theory calculations for
      61 compounds, the conjugated bases of carboxylic acids, phenols, and alcohols,
      and analyzed their acid-base behavior using molecular orbital (MO) energies and
      their dependence on solvent effects. Despite the well-known correlation between
      highest-occupied MO (HOMO) energies and pKa, we observed that HOMO energies are
      inadequate to describe the acid-base behavior of these compounds. Therefore, we
      established a criterion to identify the best frontier MO for describing pKa
      values and also to understand why the HOMO approach fails. The MO that fits our
      criterion provided very good correlations with pKa values, much better than those
      obtained by HOMO energies. Since they are the frontier molecular orbitals that
      drive the acid-base reactions in each compound, they were called frontier
      effective-for-reaction MOs, or FERMOs. By use of the FERMO concept, the reactions
      that are HOMO driven, and those that are not, can be better explained,
      independently from the calculation method used, as both HF and Kohn-Sham
      methodologies lead to the same FERMO.

PMID- 16420005
TI  - Ab initio/GIAO-CCSD(T) study of propenoyl (H2C=CH-CO+) and isopentenoyl
      ((CH3)2C=CH-CO+) cations and their superelectrophilic protonated dications.
AB  - Structures of superelectrophilic protonated propenoyl (H2C=CH-COH2+) and
      isopentenoyl ((CH3)2C=CH-COH2+) dications and their parent cations were
      calculated using ab initio methods at the MP2/6-311+G and MP2/cc-pVTZ levels.
      Energies were calculated using Gaussian-2 (G2) theory. The alpha-carbon (Calpha)
      protonated 3 and 7 were found to be the global minima for protonated propenoyl
      and isopentenoyl dications, respectively. 13C NMR chemical shifts of the cations
      were also calculated using the GIAO-CCSD(T), GIAO-MP2 and GIAO-SCF methods. 13C
      NMR chemical shifts of the related tert-butyl cation ((CH3)3C+) and protonated
      tert-butyl dication ((CH3)2CCH4(2+)) were also computed at the same level to
      compare and explore the effect of the additional charge in dications.

PMID- 16420006
TI  - Ab initio study of neutral and charged SinNap(+) (n <or= 6, p <or= 2) clusters.
AB  - Ab initio calculations in the framework of the density functional theory, with
      B3LYP functional, are performed to study the lowest-energy isomers of silicon
      sodium clusters Si(n)Na(p)(+) (n <or= 6, p <or= 2). The stability and the
      structural and electronic properties of neutral and positively charged systems
      are examined. The structure of Si(n)Na(p) keeps the frame of the corresponding
      Si(n) cluster unchanged, and the electronic structure of Si(n)Na(p) is similar to
      that of the corresponding negative system Si(n)(p-). Adsorption energies,
      vertical and adiabatic ionization potentials, electric dipole moments, and static
      dipolar polarizabilities are calculated for each considered isomer.

PMID- 16420008
TI  - Energy correctors for accurate prediction of molecular energies.
AB  - Energy correctors are introduced for the calculation of molecular energies of
      compounds containing first row atoms (Li-F) to modify ab initio molecular orbital
      calculations of energies to better reproduce experimental results. Four additive
      correctors are introduced to compensate for the differences in the treatment of
      molecules with different spin multiplicities and multiplicative correctors are
      also calculated for the electronic and zero-point vibrational energies. These
      correctors, individually and collectively yield striking improvements in the
      atomization energies for several ab initio methods. We use as training set the
      first row subset of molecules from the G1 basis of molecules; when the correctors
      are applied to other molecules not included in the training set, selected from
      the G3 basis, similar improvements in the atomization energies are obtained. The
      special case of the B3PW91/cc-pVTZ yields an average error of 1.2 kcal/mol, which
      is already within a chemical accuracy and comparable to the Gaussian-n theories
      accuracy. The very inexpensive B3PW91/6-31G** yields an average error of 2.1
      kcal/mol using the correctors. Methods considered unsuitable for energetics such
      as HF and LSDA yield corrected energies comparable to those obtained with the
      best highly correlated methods.

PMID- 16420007
TI  - Quantum chemical study of the interaction of the short-chain poly(oxyethylene)s
      CH3(OCH2CH2)mOCH3 (C1EmC1; m = 1 and 2) with a water molecule in the gas phase
      and in solutions.
AB  - It is well-known that the role of the oxygen atom of the hydrophilic unit of
      poly(oxyethylene) (POE) is one of the important factors of the high solubility of
      POE in water. In the present study, we focused on the hydration of the
      oxyethylene OCH2CH2O unit of POE, CH3(OCH2CH2)mOCH3 (C1EmC1), and theoretically
      examined the role of the water molecule on the stability of POE using the short
      chain POE, 1,2-dimethoxyethane (DME) CH3(OCH2CH2)OCH3 (C1E1C1) and diglyme
      CH3(OCH2CH2)2OCH3 (C1E2C1). The relative energies of the important conformers of
      the model POE with and without a water molecule in the gas phase and the solvent
      have been calculated by the second-order Moller-Plesset perturbation (MP2) method
      using the 6-311G basis set. We found three types of H-bonding of a water molecule
      with the POE chain for the TTT and the TGT conformers of C1E1C1 and for the
      TTTTTT, the TGTTGT, and the TGTTG'T conformers of C1E2C1, which are classified
      into the monodentate and the bidentate H-bonding. The conformers including the
      gauche form of the OCH2CH2O unit without the intramolecular electrostatic
      interaction are less stable in energy than the trans conformers in the gas phase
      for both C1E1C1 and C1E2C1. However, this order in the stability is reversed by
      the hydration. It is also found that the H-bond between POE and a water molecule
      is strengthened in the solvent. The stability of the conformers of POE in the gas
      phase and in the solvent is discussed in detail.

PMID- 16420009
TI  - Influence of N-H...O and C-H...O hydrogen bonds on the 17O NMR tensors in
      crystalline uracil: computational study.
AB  - We report a computational study for the 17O NMR tensors (electric field gradient
      and chemical shielding tensors) in crystalline uracil. We found that N-H...O and
      C-H...O hydrogen bonds around the uracil molecule in the crystal lattice have
      quite different influences on the 17O NMR tensors for the two C=O groups. The
      computed 17O NMR tensors on O4, which is involved in two strong N-H...O hydrogen
      bonds, show remarkable sensitivity toward the choice of cluster model, whereas
      the 17O NMR tensors on O2, which is involved in two weak C-H...O hydrogen bonds,
      show much smaller improvement when the cluster model includes the C-H...O
      hydrogen bonds. Our results demonstrate that it is important to have accurate
      hydrogen atom positions in the molecular models used for 17O NMR tensor
      calculations. In the absence of low-temperature neutron diffraction data, an
      effective way to generate reliable hydrogen atom positions in the molecular
      cluster model is to employ partial geometry optimization for hydrogen atom
      positions using a cluster model that includes all neighboring hydrogen-bonded
      molecules. Using an optimized seven-molecule model (a total of 84 atoms), we were
      able to reproduce the experimental 17O NMR tensors to a reasonably good degree of
      accuracy. However, we also found that the accuracy for the calculated 17O NMR
      tensors at O2 is not as good as that found for the corresponding tensors at O4.
      In particular, at the B3LYP/6-311++G(d,p) level of theory, the individual 17O
      chemical shielding tensor components differ by less than 10 and 30 ppm from the
      experimental values for O4 and O2, respectively. For the 17O quadrupole coupling
      constant, the calculated values differ by 0.30 and 0.87 MHz from the experimental
      values for O4 and O2, respectively.

PMID- 16420010
TI  - Electronic structure and molecular properties of the heptacyanorhenate [Re(CN)7]3
      and [Re(CN)7]4- complexes.
AB  - We report scalar relativistic and Dirac scattered wave (DSW) calculations on the
      heptacyanorhenate [Re(CN)7](3-) and Re(CN)7(4-) complexes. Both the ground and
      lowest excited states of each complex split by spin-orbit interaction by about
      0.3 eV. The calculated molecular electronegativities chi indicate that the open
      shell complex is less reactive than the closed-shell complex, in agreement with
      experimental observations. The calculations indicate that the ground state spin
      density is highly anisotropic and that spin-orbit effects are responsible for the
      magnetic anisotropy of the molecular g tensor of the Re(CN)7(3-) complex. The
      calculated optical electronic transitions for both complexes with a polarizable
      continuum model using a time-dependent density functional (TDDFT)/B3LYP formalism
      are in reasonable agreement with those observed in the absorption spectrum.

PMID- 16420011
TI  - X, A, B, C, and D states of the C6H5F+ ion studied using multiconfiguration wave
      functions.
AB  - Electronic states of the C6H5F+ ion have been studied within C2v symmetry by
      using the complete active space self-consistent field (CASSCF) and
      multiconfiguration second-order perturbation theory (CASPT2) methods in
      conjunction with an atomic natural orbital basis. Vertical excitation energies
      (Tv) and relative energies (Tv') at the ground-state geometry of the C6H5F
      molecule were calculated for 12 states. For the five lowest-lying states, 1(2)B1,
      1(2)A2, 2(2)B1, 1(2)B2, and 1(2)A1, geometries and vibrational frequencies were
      calculated at the CASSCF level, and adiabatic excitation energies (T0) and
      potential energy curves (PEC) for F-loss dissociations were calculated at the
      CASPT2//CASSCF level. On the basis of the CASPT2 T0 calculations, we assign the
      X, A, B, C, and D states of the ion to 1(2)B1, 1(2)A2, 2(2)B1, 1(2)B2, and
      1(2)A1, respectively, which supports the suggested assignment of the B state to
      (2)(2)B1 by Anand et al. based on their experiments. Our CASPT2 Tv and Tv'
      calculations and our MRCI T0, Tv, and Tv' calculations all indicate that the
      2(2)B1 state of C6H5F+ lies below 1(2)B2. By checking the relative energies of
      the asymptote products and checking the fragmental geometries and the charge and
      spin density populations in the asymptote products along the CASPT2//CASSCF PECs,
      we conclude that the 1(2)B1, 1(2)B2, and 1(2)A1 states of C6H5F+ correlate with
      C6H5+ (1(1)A1) + F (2P) (the first dissociation limit). The energy increases
      monotonically along the 1(2)B1 PEC, and there are barriers and minima along the
      1(2)B2 and 1(2)A1 PECs. The predicted appearance potential value for C6H5+
      (1(1)A1) is very close to the average of the experimental values. Our
      CASPT2//CASSCF PEC calculations have led to the conclusion that the 1(2)A2 state
      of C6H5F+ correlates with the third dissociation limit of C6H5+ (1(1)A2) + F
      (2P), and a preliminary discussion is presented.

PMID- 16420012
TI  - Careful scrutiny of the philicity concept.
AB  - The philicity concept [J. Phys. Chem. A 2003, 107, 4973] is put in proper
      perspective. In the present work we analyze different physicochemical problems
      using philicity. It provides satisfactory results in all such cases. We also
      compare the relative electro(nucleo)philicity with philicity to show that
      philicity is better than relative electro(nucleo)philicity when the
      intermolecular reactivity trends are considered and there is hardly any
      preference of one above the other as far as the intramolecular reactivities are
      concerned. On the contrary, the philicity concept has some advantages over the
      other concept.

PMID- 16420014
TI  - Electron localization function in full-potential representation for crystalline
      materials.
AB  - The electron localization function (ELF) is implemented in the first-principles,
      all-electron, full-potential local orbital method. This full-potential
      implementation increases the accuracy with which the ELF can be computed for
      crystalline materials. Some representative results obtained are presented and
      compared with the results of other methods. Although for crystal structures with
      directed bonding only minor differences are found, in simple elemental metals,
      there are differences in the valence region, which give rise to different ELF
      topologies.

PMID- 16420013
TI  - Complex formation of trimethylaluminum and trimethylgallium with ammonia:
      evidence for a hydrogen-bonded adduct.
AB  - We have investigated the formation of gas-phase adducts of trimethylaluminum and
      trimethylgallium with ammonia using room-temperature Fourier transform infrared
      experiments and density functional theory calculations. Our results indicate for
      the first time that, at higher partial pressures, a product distinct from the
      well-known (CH3)3M:NH3 adduct grows in for both M = Al and M = Ga. Comparison of
      the experimental and calculated IR spectra, along with calculations of the
      energetics, indicates that this second product is the result of hydrogen bonding
      of a second NH3 molecule to the (CH3)3M:NH3 adduct and can be written as
      (CH3)3M:NH3...NH3. The binding energy of this hydrogen-bonded adduct is
      calculated to be 26.8 kcal/mol for M = Al and 18.4 kcal/mol for M = Ga and is
      lower in energy (more stable) relative to the 1:1 (CH3)3M:NH3 adduct by 7.2
      kcal/mol for M = Al and 6.6 kcal/mol for M = Ga. In contrast, an alternative
      complex involving the formation of two separate M-N donor-acceptor bonds, which
      is written as H3N:(CH3)3M:NH3, is calculated to be lower in energy relative to
      (CH3)3M:NH3 by only 0.1 kcal/mol for M = Al and 0.2 kcal/mol for M = Ga and is
      not observed experimentally. These results show that hydrogen bonding plays an
      important role in the interaction of ammonia with metal organic precursors
      involving Al, Ga, and In, under typical metal organic chemical vapor deposition
      AlGaInN growth conditions.

PMID- 16420015
TI  - Alkali cation extraction by calix[4]crown-6 to room-temperature ionic liquids.
      The effect of solvent anion and humidity investigated by molecular dynamics
      simulations.
AB  - We report a molecular dynamics study on the solvation of M+ (Na+ to Cs+) alkali
      cations and of their LM+ complexes with a calix[4]arene host (L = 1,3-dimethoxy
      calix[4]arene-crown-6 in the 1,3-alternate conformation) in the [BMI][PF6] and
      [BMI][Tf2N] room-temperature ionic liquids "ILs" based on the BMI+ (1-butyl-3
      methylimidazolium) cation. The comparison of the two liquids and the dry versus
      humid form of the former one (with a 1:1 ratio of H2O and BMI+PF6- species)
      reveals the importance of humidity: in [BMI][PF6]-dry as in the [BMI][Tf2N]
      liquid, the first solvation shell of the "naked" M+ ions is composed of solvent
      anions only (four PF6- anions, and from four to five Tf2N- anions, respectively,
      quasi-neutralized by a surrounding cage of BMI+ cations), while in the [BMI][PF6]
      humid IL, it comprises from one to three solvent anions and about four H2O
      molecules. In the LM+ complexes, the cation is shielded from solvent, but still
      somewhat interacts with a solvent anion in the dry ILs and with water in the
      humid IL. We also report tests on M+ interactions with solvent anions PF6- and
      Tf2N- in the gas phase, showing that the AMBER results are in satisfactory
      agreement with QM results obtained at different levels of theory. The question of
      ion recognition by L is then examined by free energy perturbation studies in the
      three liquids, predicting a high Cs+/Na+ selectivity upon liquid extraction from
      an aqueous phase, in agreement with experimental results on a parent calixarene
      host. A similar Cs+/Na+ selectivity is predicted upon complexation in a
      homogeneous IL phase, mainly due to the desolvation energy of the free cations.
      Thus, despite their polar character, ionic liquids qualitatively behave as
      classical weakly polar organic liquids (e.g., choroform) as far as liquid-liquid
      extraction is concerned but more like polar liquids (water, alcohols) as far as
      complexation in a single phase is concerned.

PMID- 16420017
TI  - Ab initio study of hydrogen bonding and proton transfer in 3:1 FH:NH3 and
      FH:collidine complexes: structures and one- and two-bond coupling constants
      across hydrogen bonds.
AB  - Ab initio EOM-CCSD calculations have been performed on 3:1 FH:NH3 complexes at
      their own optimized MP2/6-31+G(d,p) geometries and at the optimized geometries in
      the hydrogen-bonding regions of corresponding 3:1 FH:collidine complexes. The
      isolated gas-phase equilibrium 3:1 FH:NH3 complex has an open structure with a
      proton-shared Fa-Ha-N hydrogen bond, while the isolated equilibrium 3:1
      FH:collidine complex has a perpendicular structure with an Fa-Ha-N hydrogen bond
      that is on the ion-pair side of proton-shared. The Fa-N coupling constant
      ((2h)J(Fa-N)) for the equilibrium 3:1 FH:NH3 complex is large and negative,
      consistent with a proton-shared Fa-Ha-N hydrogen bond; (2h)JFb-Fa is positive,
      reflecting a short Fb-Fa distance and partial proton transfer from Fb to Fa
      across the Fb-Hb-Fa hydrogen bond. In contrast, (2h)JFa-N has a smaller absolute
      value and (2h)JFb-Fa is greater for the 3:1 FH:NH3 complex at the equilibrium 3:1
      FH:collidine geometry, consistent with the structural characteristics of the Fa
      Ha-N and Fb-Hb-Fa hydrogen bonds. Coupling constants computed at proton
      transferred 3:1 FH:collidine perpendicular geometries are consistent with
      experimental coupling constants for the 3:1 FH:collidine complex in solution and
      indicate that the role of the solvent is to promote further proton transfer from
      Fa to N across the Fa-Ha-N hydrogen bond, and from Fb to Fa across the two
      equivalent Fb-Hb-Fa hydrogen bonds. The best correlations between experimental
      and computed coupling constants are found for complexes with perpendicular proton
      transferred structures, one having the optimized geometry of a 3:1 FH:collidine
      complex at an Fa-Ha distance of 1.80 A, and the other at the optimized 3:1
      FH:collidine geometry with distances derived from the experimental coupling
      constants. These calculations provide support for the proposed perpendicular
      structure of the 3:1 FH:collidine complex as the structure which exists in
      solution.

PMID- 16420016
TI  - Solvent-induced conformational changes of O-phenyl-cinchonidine: a theoretical
      and VCD spectroscopy study.
AB  - The conformational analysis of the synthetic chiral modifier O-phenyl
      cinchonidine (PhOCD) used in enantioselective hydrogenations over noble metal
      catalysts has been performed at a PM3 semiempirical level in vacuum. The minimum
      energy conformations calculated at the DFT level with a medium-size basis set
      have been compared to those of the parent alkaloid cinchonidine (CD). PhOCD
      behaves similarly to CD and shows four main conformers, denoted as Closed(1),
      Closed(2), Open(3), and Open(4). Open(3) is found to be the most stable in vacuum
      and in CH2Cl2 and CCl4 solvents. A comprehensive normal-mode analysis has been
      performed for these conformers, and assignment of the infrared spectrum of PhOCD
      in CCl4 (epsilon = 2.2) has been performed using the calculated spectrum of
      Open(3), which appears to be the most populated in this solvent. A combined
      theoretical-experimental VCD spectroscopy approach was used to increase the
      spectroscopic sensitivity toward changes in the distribution of conformers upon
      change of solvent polarity. The VCD spectra confirm that Open(3) is by far the
      most stable conformation in CCl4 (epsilon = 2.2) and indicate that an excess
      Closed(2) conformer has to be expected in CD2Cl2 (epsilon = 8.9). The possible
      influence of this conformational behavior is discussed on the basis of available
      catalytic data and in relation to the enantioselective potential of PhOCD as a
      chiral modifier on supported metal catalysts.

PMID- 16420018
TI  - Extending, and repositioning, a thermochemical ladder: high-level quantum
      chemical calculations on the sodium cation affinity scale.
AB  - High-level ab initio quantum chemical calculations, at the CP-dG2thaw level of
      theory, are reported for coordination of Na+ to a wide assortment of small
      organic and inorganic ligands. The ligands range in size from H to C6H6, and
      include 22 of the ligands for which precise relative sodium ion binding free
      energies have been determined by recent Fourier transform ion cyclotron resonance
      and guided ion beam studies. Agreement with the relative experimental values is
      excellent (+/-1.1 kJ mol(-1)), and agreement with the absolute scale (obtained
      when these relative values are pegged to the CH3NH2 "anchor" value measured in a
      high-pressure mass spectrometric study) is only marginally poorer, with CP
      dG2thaw values exceeding the absolute experimental DeltaG(298) values by an
      average of 2.1 kJ mol(-1). The excellent agreement between experiment and the CP
      dG2thaw technique also suggests that the additional 97 ligands surveyed here
      (which, in many cases, are not readily susceptible to laboratory investigation)
      can also be reliably fitted to the existing experimental scale. However, while CP
      dG2thaw and the experimental ladder are in close accord, a small set of higher
      level ab initio calculations on sodium ion/ligand complexes (including several
      values obtained here using the W1 protocol) suggests that the CP-dG2thaw values
      are themselves too low by approximately 2.5 kJ mol(-1), thereby implying that the
      accepted laboratory values are typically 4.6 kJ mol(-1) too low. The present work
      also highlights the importance of Na+/ligand binding energy determinations
      (whether by experimental or theoretical approaches) on a case-by-case basis:
      trends in increasing binding energy along homologous series of compounds are not
      reliably predictable, nor are binding site preferences or chelating tendencies in
      polyfunctional compounds.

PMID- 16420019
TI  - Charge-transfer pipi* excited state in the 7-azaindole dimer. A hybrid
      configuration interactions singles/time-dependent density functional theory
      description.
AB  - The hybrid configuration interaction singles/time dependent density functional
      theory approach of Dreuw and Head-Gordon [Dreuw, A.; Head-Gordon, M. J. Am. Chem.
      Soc. 2004, 126, 4007] has been applied to study the potential energy landscape
      and accessibility of the charge-transfer pipi* excited state in the dimer of 7
      azaindole, which has been traditionally considered a model for DNA base pairing.
      It is found that the charge-transfer pipi* excited state preferentially
      stabilizes the product of a single proton transfer. In this situation, the
      crossing between this state and the photoactive electronic state of the dimer is
      accessible. It is found that the charge-transfer pipi* excited state has a very
      steep potential energy profile with respect to any single proton-transfer
      coordinate and, in contrast, an extremely flat potential energy profile with
      respect to the stretch of the single proton-transfer complex. This is predicted
      to bring about a pair of rare fragments of the 7-azaindole dimer, physically
      separated and hence having very long lifetimes. This could have implications in
      the DNA base pairs of which the system is an analogue, in the form of replication
      errors.

PMID- 16420020
TI  - Electronic properties of anthracene derivatives for blue light emitting
      electroluminescent layers in organic light emitting diodes: a density functional
      theory study.
AB  - Molecular level parameters are investigated computationally to understand the
      factors that are responsible for the higher efficiency in derivatives of 9,10
      bis(1-naphthyl)anthracene (alpha-ADN), 9,10-bis(2-naphthyl)anthracene (beta-ADN),
      their tetramethyl derivatives (alpha,beta-TMADN) and the t-Bu derivative (beta
      TBADN) as blue light emitting electroluminescent (EL) layers in organic light
      emitting diodes (OLEDs). DFT studies at the B3LYP/6-31G(d,p) level have been
      carried out on the substituted anthracenes. The absorption spectra are simulated
      using time dependent DFT methods (TD-DFT) whereas the emission spectra are
      approximated by optimizing the excited state by HF/CI-Singles and then carrying
      out the vertical CI calculations by the TD-DFT method. The reorganization energy
      for estimating the hole and electron transport is calculated. The transfer
      integrals between parallely stacked molecules in the bulk state are estimated by
      calculating the electronic splitting. The substituted anthracenes are compared
      with unsubstituted anthracene and yet untested 9,10-dianthrylanthracene (TANTH).
      A larger and slower buildup of the electrons and holes in the EL layer, due to
      the higher reorganization energy and smaller electronic coupling between the
      adjacent molecules could lead to an increase in hole-electron recombination in
      the layer and thus increase the efficiency.

PMID- 16420021
TI  - Radical cations from dicyclopropylidenemethane and its octamethyl derivative.
AB  - The radical cations of dicyclopropylidenemethane (2) and its octamethyl
      derivative (2-Me8) are prone to rearrangements into those of (2
      methylallylidene)cyclopropane (2a) and its octamethyl derivative (2a-Me8),
      respectively, by opening one three-membered ring. In contrast to the radical
      cations of bicyclopropylidene (1) and its octamethyl derivative (1-Me8), 2*+ and
      2-Me8*+ are stable to opening of the second ring, because in this case the
      resulting species would be a non-Kekule hydrocarbon with a quartet ground state.
      Similarly to 1, octamethyl substitution in 2 promotes the tendency to
      rearrangement. Thus, ESR and ENDOR studies indicate that the primary radical
      cation 2*+, which is formed upon gamma-irradiation of 2 in a CFCl3 matrix at 77
      K, does not rearrange up to 150 K. On the other hand, when 2-Me8 is treated in
      the same way, only the rearranged radical cation 2a-Me8*+ can be observed and
      characterized by its ESR and ENDOR spectra. Nevertheless, the existence of the
      two "missing" species, 2a*+ and 2-Me8*+, is revealed by other methods. According
      to UV and IR studies, X irradiation of 2 in an Ar matrix leads directly to the
      ring-opened radical cation 2a*+. Moreover, magnetic field effects on the decay of
      fluorescence, which appears upon recombination of the radical anion of p
      terphenyl with a radical cation generated from 2-Me8 in liquid octane, strongly
      suggest that 2-Me8*+ (and not 2a-Me8*+) is formed initially. From the temperature
      dependence of the decay, the activation energy of the ring-opening process 2
      Me8*+ --> 2a-Me8*+ is estimated. The radical cations 2a*+ and 2a-Me8*+ are
      formally distonic with the spin residing in the allylic moiety and the charge
      accommodated on the central carbon atom of the allene pi-system. The intact
      cyclopropylidenemethylidene moiety assumes a "bisected" conformation, thus
      favoring an optimal interaction with the positively charged center on the pi
      system.

PMID- 16420022
TI  - Electronic structure and redox properties of the open-shell metal-carbide
      endofullerene Sc3C2@C80: a density functional theory investigation.
AB  - Density functional theory calculations have shown that the open-shell metal
      carbide endofullerene Sc3C2@C80 has the valence state (Sc3+)3(C2)(3-)@C80(6-). A
      lot of low-lying isomers differing in geometries and locations of the endohedral
      [(Sc3+)3(C2)(3-)] cluster have been located, indicating unusual dual
      intramolecular dynamic behaviors of this endofullerene at room temperature. The
      electrochemical redox properties of this endofullerene have been elucidated in
      terms of electronic structure theory. Its redox states are found to follow the
      general charge-state formula (Sc3+)3C2(3-q)-@C80(6-) (q is the charge of the
      whole molecule ranging from +1 to -3), demonstrating the high charge flexibility
      of the endohedral metal-carbide cluster. The structure of the endohedral
      [(Sc3+)3C2(3-q)-)] cluster varies with the redox processes, shifting from a
      planar structure (for q = 0 and -1) to a trifoliate structure (for q = +1, -2, 
      3).

PMID- 16420023
TI  - [2.2]paracyclophane-bridged mixed-valence compounds: application of a generalized
      Mulliken-Hush three-level model.
AB  - A series of [2.2]paracylophane-bridged bis-triarylamine mixed-valence (MV)
      radical cations were analyzed by a generalized Mulliken-Hush (GMH) three-level
      model which takes two transitions into account: the intervalence charge transfer
      (IV-CT) band which is assigned to an optically induced hole transfer (HT) from
      one triarylamine unit to the second one and a second band associated with a
      triarylamine radical cation to bridge (in particular, the [2.2]paracyclophane
      bridge) hole transfer. From the GMH analysis, we conclude that the
      [2.2]paracyclophane moiety is not the limiting factor which governs the
      intramolecular charge transfer. AM1-CISD calculations reveal that both through
      bond as well as through-space interactions of the [2.2]paracyclophane bridge play
      an important role for hole transfer processes. These electronic interactions are
      of course smaller than direct pi-conjugation, but from the order of magnitude of
      the couplings of the [2.2]paracyclophane MV species, we assume that this bridge
      is able to mediate significant through-space and through-bond interactions and
      that the cyclophane bridge acts more like an unsaturated spacer rather than a
      saturated one. From the exponential dependence of the electronic coupling V
      between the two triarylamine localized states on the distance r between the two
      redox centers, we infer that the hole transfer occurs via a superexchange
      mechanism. Our analysis reveals that even significantly longer pi-conjugated
      bridges should still mediate significant electronic interactions because the
      decay constant beta of a series of pi-conjugated MV species is small.

PMID- 16420024
TI  - Inelastic neutron scattering study of water in hydrated LTA-type zeolites.
AB  - The vibrational dynamics of water molecules encapsulated in synthetic Na-A and Mg
      exchanged A zeolites were studied versus temperature by inelastic neutron
      scattering (INS) measurements (30-1200 cm(-1)) as a function of the induced ion
      exchange percentage by using the indirect geometry tof spectrometer TOSCA at the
      ISIS pulse neutron facility (RAL, UK). The experimental INS spectra were compared
      with those of ice Ih to characterize the structural changes induced by
      confinement on the H2O hydrogen-bonded network. We observed, after increasing the
      Mg2+ content, a tendency of water molecules to restore the bulklike arrangements
      together with more hindered dynamics. These results are confirmed by the analysis
      of the evaluated one-phonon amplitude-weighted proton vibrational density of
      states aimed, in particular, to follow the evolution of the water molecules
      librational mode region.

PMID- 16420025
TI  - Multi-frequency ESR study of the polycrystalline phenoxyl radical of alpha-(3,5
      di-tert-butyl-4-hydroxyphenyl)-N-tert-butylnitrone in the diamagnetic matrix.
AB  - Multifrequency (X-, Q-, and W-band) electron spin resonance (ESR) spectroscopy
      has been used to characterize the phenoxyl radical produced from alpha-(3,5-di
      tert-butyl-4-hydroxyphenyl)-N-tert-butylnitrone, which is a new spin-trapping
      reagent. The X-band measurement did not resolve the powder-pattern ESR spectrum.
      Because of its higher resolution with g value, the Q-band ESR study revealed that
      the g factor has an axial-like symmetry and that the observed hyperfine structure
      in the Z-direction is caused by the nitrogen nucleus at the para-position.
      Furthermore, the results of the W-band ESR experiment more clearly distinguished
      the perpendicular components from the parallel component, resolving the
      perpendicular components into x and y components. The X-band powder spectrum was
      similar to the X-band ESR spectrum of the radical in a frozen solution of
      toluene. The computer simulation spectra performed using the obtained parameters
      fitted the experimental spectra well. A comparison of the amplitude of g(
      perpendicular)(gx, gy) with that of gz showed that the unpaired electron is
      delocalized over the pi-conjugated framework. Considering the hyperfine coupling
      constant, it was concluded that about 16% of the unpaired electron distributed
      over the nitrogen nucleus at the para-position. This study thus showed the
      significant potential of a multifrequency ESR approach to a powder sample radical
      in terms of its high resolution with g value.

PMID- 16420026
TI  - Potent and selective mitogen-activated protein kinase kinase (MEK) 1,2
      inhibitors. 1. 4-(4-bromo-2-fluorophenylamino)-1- methylpyridin-2(1H)-ones.
AB  - The role of MEK 1,2 in cancer tumorgenesis has been clearly demonstrated
      preclinically, and two selective inhibitors are currently undergoing clinical
      evaluation to determine their role in the human disease. We have discovered 4-(4
      bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones as a new class of ATP
      noncompetitive MEK inhibitors. These inhibitors exhibit excellent cellular
      potency and good pharmacokinetic properties and have demonstrated the ability to
      inhibit ERK phosphorylation in HT-29 tumors from mouse xenograft studies.

PMID- 16420029
TI  - Novel potential anticancer naphthyl phosphoramidates of BVdU: separation of
      diastereoisomers and assignment of the absolute configuration of the phosphorus
      center.
AB  - We have previously reported our SAR optimization of the anticancer agent
      thymectacin. Tuning of the parent ProTide structure initially involved the amino
      acid and, subsequently, the aromatic masking group on the phosphate moiety.
      Herein, derivatives bearing the combined modifications are reported and
      biological evaluation is described. Moreover, separation of the diastereoisomeric
      final product mixture shows a different cytostatic activity for the two
      diastereoisomers. Through computational and NMR studies, the absolute
      stereochemistry of the phosphorus center of the two diastereoisomers has been
      suggested.

PMID- 16420027
TI  - HIV integrase inhibitors with nucleobase scaffolds: discovery of a highly potent
      anti-HIV agent.
AB  - HIV integrase is essential for HIV replication. However, there are currently no
      integrase inhibitors in clinical use for AIDS. We have discovered a conceptually
      new beta-diketo acid that is a powerful inhibitor of both the 3'-processing and
      strand transfer steps of HIV-1 integrase. The in vitro anti-HIV data of this
      inhibitor were remarkable as exemplified by its highly potent antiviral
      therapeutic efficacy against HIV(TEKI) and HIV-1(NL4)(-)(3) replication in PBMC
      (TI >4,000 and >10,000, respectively).

PMID- 16420028
TI  - A minimalist design approach to antimicrobial agents based on a thionin template.
AB  - Numerous studies have been devoted to the stabilization of secondary structure
      elements to improve receptor-ligand recognition. We report a novel application of
      this principle to create new antimicrobial agents using the highly folded thionin
      from Pyrularia puberaas a template. Non-native disulfide bonds have been used to
      induce two short linear segments of the protein into an amphipathic helix. The
      resulting 13- and 9-residue peptides are significantly more active than their
      linear counterparts and have an activity similar to that of native thionin.

PMID- 16420030
TI  - Selective inhibition of matrix metalloproteinase isozymes and in vivo protection
      against emphysema by substituted gamma-keto carboxylic acids.
AB  - The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a series
      of gamma-keto carboxylic acids are described. Among nine MMP isozymes tested,
      compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50)
      values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it
      shows protection against PPE-induced emphysema.

PMID- 16420031
TI  - Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with
      improved acetylcholinesterase inhibitory and antioxidant properties.
AB  - Tacrine and melatonin are well-known drugs with activities as an
      acetylcholinesterase (AChE) inhibitor and free radical scavenger, respectively.
      In this work, we report new hybrids of both drugs that display higher in vitro
      properties than the sum of their parts. As selective inhibitors of human AChE,
      their IC(50) values range from sub-nanomolar to picomolar. They exhibit a higher
      oxygen radical absorbance capacity than does melatonin and are predicted to be
      able to cross the blood-brain barrier to reach their targets in the central
      nervous system.

PMID- 16420033
TI  - Rapid synthesis of triazole-modified resveratrol analogues via click chemistry.
AB  - Resveratrol is a phytoalexin able to display an array of biological activities.
      We decided to replace the double bond with a triazole ring using the archetypical
      click reaction: the Huisgen [3 + 2] cycloaddition. Seventy-two triazole
      derivatives were synthesized via a parallel combinatorial approach. Preliminary
      data suggest that this procedure can lead to the synthesis of compounds that
      display some, but not all, of resveratrol's actions with increased potency.

PMID- 16420032
TI  - Targeting FtsZ for antituberculosis drug discovery: noncytotoxic taxanes as novel
      antituberculosis agents.
AB  - Screening of 120 taxanes identified a number of compounds that exhibited
      significant antituberculosis activity. Rational optimization of selected
      compounds led to the discovery that the C-seco-taxane-multidrug-resistance (MDR)
      reversal agents (C-seco-TRAs) are noncytotoxic at the upper limit of solubility
      and detection (>80 microM), while maintaining MIC(99) values of 1.25-2.5 microM
      against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis
      (MTB). Treatment of MTB cells with TRA 3aa and 10a at the MIC caused
      filamentation and prolongation of the cells, a phenotypic response to FtsZ
      inactivation.

PMID- 16420034
TI  - Identification and biological characterization of 6-aryl-7
      isopropylquinazolinones as novel TRPV1 antagonists that are effective in models
      of chronic pain.
AB  - Vanilloid receptor 1 (VR1, TRPV1) is a cation-selective ion channel that is
      expressed on primary afferent neurons and is upregulated following inflammation
      and nerve damage. Blockers of this channel may have utility in the treatment of
      chronic nociceptive and neuropathic pain. Here, we describe the optimization from
      a high throughput screening hit, of a series of 6-aryl-7-isopropylquinazolinones
      that are TRPV1 antagonists in vitro. We also demonstrate that one compound is
      active in vivo against capsaicin-induced hyperalgesia and in models of
      neuropathic and nociceptive pain in the rat.

PMID- 16420035
TI  - Insight into the structural requirements of urokinase-type plasminogen activator
      inhibitors based on 3D QSAR CoMFA/CoMSIA models.
AB  - Urokinase-type plasminogen activator (uPA), a trypsin-like serine protease, has
      been implicated in large number of malignancies, tumor cell invasion,
      angiogenesis and metastasis; hence, the potent and selective inhibitors of uPA
      may therefore be therapeutically useful drugs for treatment of various forms of
      cancer. A three-dimensional quantitative structure-activity relationship (3D
      QSAR) study was performed on five different chemical series reported as selective
      uPA inhibitors employing comparative molecular field analysis (CoMFA)/comparative
      molecular similarity indices analysis (CoMSIA) techniques to investigate the
      structural requirements for substrates and derive a predictive model that may be
      used for the design of novel uPA inhibitors. ClogP has been used as an additional
      descriptor in the CoMFA analysis to study the effects of lipophilic parameters on
      activity. Inclusion of ClogP did not improve the models significantly and
      exhibited comparable correlation coefficients with CoMFA steric and electrostatic
      models. 3D QSAR models were derived for 2-pyridinylguanidines (training set N =
      25, test set N = 8), 4-aminoarylguanidines and 4-aminoarylbenzamidines (training
      set N = 29, test set N = 8), thiophene-2-carboxamindines (training set N = 64,
      test set N = 19), 2-naphthamidines (training set N = 32, test set N = 8), and 1
      isoquinolinylguanidines (training set N = 29, test set N = 7). The CoMFA models
      with steric and electrostatic fields exhibited r(2)(cv) 0.452-0.722, r(2)(ncv)
      0.812-0.986, r(2)(pred) 0.597-0.870, whereas CoMFA ClogP models showed r(2)(cv)
      0.420-0.707, r(2)(ncv) 0.849-0.957, r(2)(pred) 0.600-0.870. The CoMSIA models
      displayed r(2)(cv) 0.663-0.729, r(2)(ncv) 0.909-0.998, r(2)(pred) 0.554-0.855. 3D
      contour maps generated from these models were analyzed individually, which
      provides the regions in space where interactive fields may influence the
      activity. The superimposition of contour maps on the active site of serine
      proteases additionally helps in understanding the structural requirements of
      these inhibitors. Further, the predictive ability of 3D QSAR models was affirmed
      by predicting the activity of novel 2-naphthamidines. 3D QSAR models developed
      may be used in designing and predicting the uPA inhibitory activity of novel
      molecules.

PMID- 16420036
TI  - Knowledge-based design of target-focused libraries using protein-ligand
      interaction constraints.
AB  - Here we present a new strategy for designing and filtering potentially massive
      combinatorial libraries using structural information of a binding site. We have
      developed a variation of the structural interaction fingerprint (SIFt) named r
      SIFt, which incorporates the binding interactions of variable fragments in a
      combinatorial library. This method takes into account the 3D structure of the
      active site of the target molecule and translates desirable ligand-target binding
      interactions into library filtering constraints. We show using the MAP kinase p38
      as a test case that we can efficiently analyze and classify compounds on the
      basis of their abilities to interact with the target in the desired binding mode.
      On the basis of these classifications, decision tree models were generated using
      the molecular descriptors of the compounds as predictor variables. Our results
      suggest that r-SIFt coupled with the classification models should be a valuable
      tool for structure-based focusing of combinatorial chemical libraries.

PMID- 16420037
TI  - Computational study of antagonist/alpha1A adrenoceptor complexes--observations of
      conformational variations on the formation of ligand/receptor complexes.
AB  - As selective antagonist inhibition may relieve the symptoms of benign prostatic
      hyperplasia, we have examined the interactions of antagonists including
      quinazoline and imidazolidinium/guanidinium compounds complexed with a homology
      model of the alpha(1A) adrenoceptor. Our approach involves docking of ligands of
      various structural classes followed by molecular dynamics simulations of
      antagonist/receptor complexes, which demonstrates that different structural
      classes of antagonist induce different receptor conformations upon binding with
      particular variations noted in the conformation of TM-V. Subsequently, we
      examined the interactions and the conformational flexibility of alpha(1) and
      alpha(1A) adrenoceptor antagonists, with the ligand-induced receptor conformers.
      This study indicated that a receptor conformation induced by one structural class
      of antagonist is not suitable for direct screening of another class. Our analysis
      indicates that computational high-throughput screening is likely to give
      inaccurate data on binding and selectivity and such studies need to consider
      conformational changes in the receptor.

PMID- 16420038
TI  - Metal-mediated inhibition of Escherichia coli methionine aminopeptidase:
      structure-activity relationships and development of a novel scoring function for
      metal-ligand interactions.
AB  - We report the discovery of thiabendazole as a potent inhibitor (K(i) = 0.4
      microM) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis
      and pharmacological evaluation of thiabendazole congeners with activity in the
      upper nanomolar range. Elucidation of the X-ray structure of ecMetAP in complex
      with thiabendazole and an unrelated inhibitor that was independently described by
      another group showed that that both compounds bind to an additional Co(II) ion at
      the entrance of the active site. This unexpected finding explains the inactivity
      of the compounds under in vivo conditions. It also allows us to discuss the
      structure-activity relationships of this series of compounds in a meaningful way,
      based upon docking runs with an auxiliary metal ion. We describe a new scoring
      function for the evaluation of metal-mediated inhibitor binding that, unlike the
      previously used scoring function implemented in the docking program, allows us to
      distinguish between active and inactive compounds. Finally, conclusions for the
      structure-based design of in vivo-active inhibitors of ecMetAP are drawn.

PMID- 16420039
TI  - Classification of chemical compounds by protein-compound docking for use in
      designing a focused library.
AB  - We developed a new method for the classification of chemical compounds and
      protein pockets and applied it to a random screening experiment for macrophage
      migration inhibitory factor (MIF). The principal component analysis (PCA) method
      was applied to the protein-compound interaction matrix, which was given by
      thorough docking calculations between a set of many protein pockets and chemical
      compounds. Each compound and protein pocket was depicted as a point in the PCA
      spaces of compounds and proteins, respectively. This method was applied to
      distinguish active compounds from negative compounds of MIF. A random screening
      experiment for MIF was performed, and our method revealed that the active
      compounds were localized in the PCA space of compounds, while the negative
      compounds showed a wide distribution. Furthermore, protein pockets, which bind
      similar compounds, were classified and were found to form a cluster in the PCA
      space.

PMID- 16420040
TI  - Novel procedure for modeling ligand/receptor induced fit effects.
AB  - We present a novel protein-ligand docking method that accurately accounts for
      both ligand and receptor flexibility by iteratively combining rigid receptor
      docking (Glide) with protein structure prediction (Prime) techniques. While
      traditional rigid-receptor docking methods are useful when the receptor structure
      does not change substantially upon ligand binding, success is limited when the
      protein must be "induced" into the correct binding conformation for a given
      ligand. We provide an in-depth description of our novel methodology and present
      results for 21 pharmaceutically relevant examples. Traditional rigid-receptor
      docking for these 21 cases yields an average RMSD of 5.5 A. The average ligand
      RMSD for docking to a flexible receptor for the 21 pairs is 1.4 A; the RMSD is <
      or =1.8 A for 18 of the cases. For the three cases with RMSDs greater than 1.8 A,
      the core of the ligand is properly docked and all key protein/ligand interactions
      are captured.

PMID- 16420041
TI  - 3D-QSAR studies on cannabinoid CB1 receptor agonists: G-protein activation as
      biological data.
AB  - G-protein activation via the CB1 receptor was determined for a group of various
      CB1 ligands and utilized as biological activity data in subsequent CoMFA and
      CoMSIA studies. Both manual techniques and automated docking at CB1 receptor
      models were used to obtain a common alignment of endocannabinoid and classical
      cannabinoid derivatives. In the final alignment models, the endocannabinoid
      headgroup occupies a unique region distinct from the classical cannabinoid
      structures, supporting the hypothesis that these structurally diverse molecules
      overlap only partially within the receptor binding site. Both CoMFA and CoMSIA
      produce statistically significant models based on the manual alignment and a
      docking alignment at one receptor conformer. Leave-half-out cross-validation and
      progressive scrambling were successfully used in assessing the predictivity of
      the QSAR models.

PMID- 16420042
TI  - Potent 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-based
      macrocyclic inhibitors of hepatitis C virus NS3 protease.
AB  - The NS3 protease of hepatitis C virus (HCV) has emerged as one of the best
      characterized targets for next-generation HCV therapy. The tetrapeptide 1 and
      pentapeptide 2 are alpha-ketoamide-type HCV serine protease inhibitors with
      modest potency. We envisioned that the 1,2,3,4-tetrahydroisoquinoline-3
      carboxylamide (Tic) moiety could be cyclized to the P3 capping group. The
      resulting macrocycle could enhance the binding through its extra contact with the
      Ala156 methyl group. Macrocyclization could also provide a less peptidic HCV
      inhibitor. Synthesis started from dipeptide 5, which was obtained via a coupling
      of two amino acid derivatives. The N-terminal was capped as hept-6-enoylamide to
      give 6. Hydroboration of the double bond afforded alcohol 7, the precursor to the
      macrocycle 8. The macrocyclization was achieved under Mitsunobu conditions
      (PPh(3), ADDP). The macrocyclic acid 9 was then combined with appropriate right
      hand fragments 12, 14, or 16, which was prepared from common intermediate 11.
      Finally, oxidation of alpha-hydroxyamide provided target molecule alpha
      ketoamides 17, 18, and 21. The C-terminal esters were then elaborated to
      carboxylic acids 19 and 20, and amides 20 and 23. The inhibitors 17-23 were
      tested in HCV NS3 protease continuous assay. Tripeptide 17 was more potent than
      the larger acyclic tetrapeptide 1. The tetrapeptides 18-20 were as active as 17.
      Most significantly, the pentapeptides (21-23) were much better inhibitors (K(i) =
      0.015-0.26 microM). The carboxylic acid (22) and amide (23) were 57-80 times more
      potent than the acyclic analogue 2. The X-ray crystal structure of compound 23
      bound to the protease revealed that the macrocycle adopted a donutlike
      conformation and had close contact with the Ala156 methyl group. The ketone
      carbonyl formed a reversible covalent bond with Ser139. The n-propyl of P1
      novaline and the aromatic ring of P2' phenylglycine formed a C-shaped clamp
      around the Lys136 side chain.

PMID- 16420043
TI  - Synthesis, chiral resolution, and enantiopharmacology of a potent 2,3
      benzodiazepine derivative as noncompetitive AMPA receptor antagonist.
AB  - This paper describes the synthesis of racemic 3,5-dihydro-5-methyl-7,8
      methylenedioxy-4H-2,3-benzodiazepin-4-one (+/-)-5, attempted stereoselective
      synthesis of its enantiomers, chiral HPLC resolution of the racemate, and
      assignment of the absolute configuration. Enantiomer (5S)-(-)-5 is provided with
      an in vivo anticonvulsant activity 8 times higher than its enantiomer (5R)-(+)-5.
      This result is confirmed in the in vitro test by the ability to inhibit the
      kainate-induced increase of the [Ca(2+)](i) in a primary culture of rat
      cerebellar granule cells which express alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptors. Binding affinity of compound (+/-)-5 at the AMPA
      and N-methyl-d-aspartic acid (NMDA) receptors was also evaluated.

PMID- 16420045
TI  - 4-(3'alpha15'beta-dihydroxy-5'beta-estran-17'beta-yl)furan-2-methyl alcohol: an
      anti-digoxin agent with a novel mechanism of action.
AB  - The synthesis and some pharmacological properties of 4-(3'alpha-15'beta-dihydroxy
      5beta-estran-17'beta-yl)furan-2-methyl alcohol (16) have been described. The
      compound was synthesized by reacting a synthetic 3alpha- benzyloxy-5beta-estr-15
      en-17-one with the ethylene acetal of 4-bromo-2-furancarboxyaldehyde, followed by
      hydrolysis of the ethylene acetal and reduction of the aldehyde. Despite its
      resemblance to the structure of cardiac steroids (CS), 16 does not bind to the CS
      receptor on Na(+),K(+)-ATPase and does not increase the force of contraction of
      heart muscle. However, 16 inhibited the digoxin-induced increase in the force of
      contraction and arrhythmias in guinea pig papillary muscle and human atrial
      appendages. The steroid also inhibited digoxin-induced alteration in endocytosed
      membrane traffic, indicating a novel mechanism of action.

PMID- 16420044
TI  - Trisubstituted acridines as G-quadruplex telomere targeting agents. Effects of
      extensions of the 3,6- and 9-side chains on quadruplex binding, telomerase
      activity, and cell proliferation.
AB  - The synthesis is reported of a group of 3,6,9-trisubstituted acridine compounds
      as telomeric quadruplex-stabilizing ligands with systematic variations at the 3-,
      6-, and 9-positions. A new microwave-assisted methodology has been developed for
      trisubstituted acridine synthesis. Structure-activity relationships are reported
      using surface plasmon resonance and a fluorescence melting assay to examine
      quadruplex binding, together with a telomerase inhibition assay. These reveal
      relationships between G-quadruplex stabilization and telomerase inhibition and
      optimal 3,6- and 9-substituent side-chain lengths for maximal activity.
      Qualitative molecular modeling using molecular dynamics simulations has been
      undertaken on four quadruplex-DNA complexes. Long-term exposure of MCF7 cancer
      cells to a subset of the most active compounds, at doses lower than the IC(50)
      values, showed that one compound produced a marked decrease in population growth,
      accompanied by senescence, which is consistent with telomere targeting by this
      agent.

PMID- 16420046
TI  - Library design, synthesis, and screening: pyridine dicarbonitriles as potential
      prion disease therapeutics.
AB  - Transmissible spongiform encephalopathies (TSEs) or prion diseases are a family
      of invariably fatal neurodegenerative disorders, and there are no effective
      therapeutics currently available. In this paper, we report on the design,
      synthesis, and screening of a series of pyridine dicarbonitriles as potential
      novel prion disease therapeutics. A virtual reaction-based library of 1050
      compounds was constructed. Docking and evaluation using GOLD scores assisted the
      initial selection of compounds for synthesis. The selection was augmented with
      further compounds to increase structural diversity. A total of 45 compounds were
      synthesized via a one-pot three-component coupling reaction. The mechanism of the
      three-component coupling reaction was investigated, and it was discovered that
      chemical oxidation is required for the last step, forming the pyridine ring
      (aromatization). A total of 19 compounds were identified as binders to one or
      more forms of prion protein by in vitro screening using surface plasmon resonance
      (SPR). A selection of compounds were investigated for activity in cells,
      resulting in the discovery of a new inhibitor of PrP(Sc) formation.

PMID- 16420047
TI  - Identification of the key residue of calcitonin gene related peptide (CGRP) 27-37
      to obtain antagonists with picomolar affinity at the CGRP receptor.
AB  - Calcitonin gene related peptide (CGRP) plays an important role in the CNS and in
      the cardiovascular system. To identify high-affinity antagonists in competitive
      binding studies, we identified a novel radioactive tracer, [(3)H-propionyl-K(24)]
      halphaCGRP 8-37, which was labeled in solution by a recently developed strategy
      using photolabile protecting groups at reactive side chains. This tracer was
      shown to be as potent as commercially available (125)I-tracers for the
      determination of agonists and to have increased sensitivity for antagonists. We
      applied it to investigate the predicted turn structures centered at Pro(29) and
      Pro(34). The substitution at positions 29 and 34 by turn-inducing amino acid
      mimetica showed that these turns are highly diverse. At position 29, a
      hydrophobic residue is preferred that constricts the secondary structure, whereas
      position 34 is required to stabilize the conformation of the backbone. All high
      affinity analogues showed antagonistic properties with potency similar to CGRP 8
      37.

PMID- 16420048
TI  - 3D-QSAR studies of arylpyrazole antagonists of cannabinoid receptor subtypes CB1
      and CB2. A combined NMR and CoMFA approach.
AB  - The present work focuses on the study of the three-dimensional (3D) structural
      requirements for selective antagonist activity of arylpyrazole compounds at the
      cannabinoid CB1 and CB2 receptors. Initially, a combined high-resolution two
      dimensional (2D) NMR and computer modeling approach was carried out to study the
      solution structure of the key pyrazole derivative N-(piperidin-1-yl)-5-phenyl-1
      (n-pentyl)-4-methyl-1H-pyrazole-3-carboxamide (AM263). By using the NMR
      determined molecular conformers as templates, the 3D quantitative structure
      activity relationship (QSAR) studies were performed with the comparative
      molecular field analysis (CoMFA) approach on a set of arylpyrazole cannabinoid
      receptor antagonists. Molecular alignments suitable for deriving valuable
      pharmacophoric features for this series of compounds were determined. Such
      systematic 3D-QSAR/CoMFA analyses of 29 molecules and their receptor affinities
      gave guidance for understanding the binding affinities of arylpyrazoles at the
      CB1 and CB2 binding sites, respectively. Comparison of CoMFA steric and potential
      contour maps for affinity at the two cannabinoid receptor subtypes helps to
      differentiate structural requirements for each subtype and serves as a basis for
      the design of later-generation analogues.

PMID- 16420049
TI  - Overlapping, nonidentical binding sites of different classes of nonpeptide
      antagonists for the human gonadotropin-releasing hormone receptor.
AB  - Peptide agonists and antagonists of the human gonadotropin-releasing hormone
      receptor (GnRH-R) are widely used to treat a range of reproductive hormone
      related diseases. Recently, nonpeptide, orally available GnRH-R antagonists have
      emerged from several chemical classes. To understand how a relatively large
      peptide-binding pocket can recognize numerous nonpeptide ligands, we undertook a
      systematic mapping of GnRH-R residues involved in the binding of three nonpeptide
      antagonists. A region composed of the extracellular portions of transmembrane
      helices 6 and 7, extracellular loop 3, and the N-terminal domain significantly
      contributed to nonpeptide antagonist binding. However, each molecule was affected
      by a different subset of residues in these regions, indicating that each appears
      to occupy distinct, partially overlapping subregions within the more extensive
      peptide-binding pocket. Moreover, the resulting receptor interaction maps provide
      a basis to begin to reconcile structure-activity relationships between various
      nonpeptide and peptide series and facilitate the design of improved therapeutic
      agents.

PMID- 16420050
TI  - Protein-protein interactions: modeling the hepatitis C virus ion channel p7.
AB  - The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the
      hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2,
      and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1
      and TM2 was estimated by employing different secondary structure prediction
      algorithms and is proposed to span from Ala-10 to Leu-32 for TM1 and from Trp-36
      to Pro-58 for TM2. A configurational search protocol based on simulated annealing
      combined with short restrained molecular dynamics simulations is used in addition
      to protein-protein docking to investigate the packing of TM1/TM2. Full p7
      oligomeric bundles were generated, and in the most plausible models serines and
      threonines are facing the hydrophilic pore. In these models, His-17 would be a
      pore-facing residue, suggesting that p7 may be sensitive to pH in respect to its
      function.

PMID- 16420051
TI  - Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xL from NMR and
      parallel synthesis.
AB  - The antiapoptotic proteins Bcl-x(L) and Bcl-2 play key roles in the maintenance
      of normal cellular homeostasis. However, their overexpression can lead to
      oncogenic transformation and is responsible for drug resistance in certain types
      of cancer. This makes Bcl-x(L) and Bcl-2 attractive targets for the development
      of potential anticancer agents. Here we describe the structure-based discovery of
      a potent Bcl-x(L) inhibitor directed at a hydrophobic groove on the surface of
      the protein. This groove represents the binding site for BH3 peptides from
      proapoptotic Bcl-2 family members such as Bak and Bad. Application of NMR-based
      screening yielded an initial biaryl acid with an affinity (K(d)) of approximately
      300 microM for the protein. Following the classical "SAR by NMR" approach, a
      second-site ligand was identified that bound proximal to the first-site ligand in
      the hydrophobic groove. From NMR-based structural studies and parallel synthesis,
      a potent ligand was obtained, which binds to Bcl-x(L) with an inhibition constant
      (K(i)) of 36 +/- 2 nM.

PMID- 16420052
TI  - The first potent inhibitors for human glutaminyl cyclase: synthesis and structure
      activity relationship.
AB  - The first effective inhibitors for human glutaminyl cyclase (QC) are described.
      The structures are developed by applying a ligand-based optimization approach
      starting from imidazole. Screening of derivatives of that heterocycle led to
      compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library
      of thiourea derivatives was synthesized, resulting in an inhibitory improvement
      by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4
      dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the
      scaffold revealed a strong impact on the inhibitory efficacy and resulted in the
      development of imidazole-propyl-thioamides as another new class of potent
      inhibitors. A flexible alignment of the most potent compounds of the thioamide
      and thiourea class and a QC substrate revealed a good match of characteristic
      features of the molecules, which suggests a similar binding mode of both
      inhibitors and the substrate to the active site of QC.

PMID- 16420053
TI  - Discovery of two novel, small-molecule inhibitors of DNA methylation.
AB  - DNA methyltransferases are promising targets for cancer therapy. In many cancer
      cells promoters of tumor suppressor genes are hypermethylated, which results in
      gene inactivation. It has been shown that DNA methyltransferase inhibitors can
      suppress tumor growth and have significant therapeutic value. However, the
      established inhibitors are limited in their application due to their substantial
      cytotoxicity. To discover novel compounds for the inhibition of human DNA
      methyltransferases, we have screened a set of small molecules available from the
      NCI database. Using a 3-dimensional model of the human DNA methyltransferase 1
      and a modified docking and scoring procedure, we have identified a small list of
      molecules with high affinities for the active site of the enzyme. The two highest
      scoring structures were found to inhibit DNA methyltransferase activity in vitro
      and in vivo. The newly discovered inhibitors validate our screening procedure and
      also provide a useful basis for further rational drug development.

PMID- 16420054
TI  - Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase
      inhibitors.
AB  - A screen of indole-based structures revealed the natural product brassinin to be
      a moderate inhibitor of indoleamine 2,3-dioxygenase (IDO), a new cancer
      immunosuppression target. A structure-activity study was undertaken to determine
      which elements of the brassinin structure could be modified to enhance potency.
      Three important discoveries have been made, which will impact future IDO
      inhibitor development: (i) The dithiocarbamate portion of the brassinin lead is a
      crucial moiety, which may be binding to the heme iron of IDO; (ii) an indole ring
      is not necessary for IDO inhibition; and (iii) substitution of the S-methyl group
      of brassinin with large aromatic groups provides inhibitors that are three times
      more potent in vitro than the most commonly used IDO inhibitor, 1-methyl
      tryptophan.

PMID- 16420055
TI  - Miliusanes, a class of cytotoxic agents from Miliusa sinensis.
AB  - Bioassay-directed fractionation of the leaves, twigs, and flowers of Miliusa
      sinensis Finet and Gagnep. (Annonaceae) led to the isolation of a new class of
      potential anticancer lead molecules. They are a cluster of compounds composed of
      a C(18) carbon skeleton, a known but heretofore unnamed type, which we have
      designated as miliusane. Two known (1 and 2) as well as 20 new miliusanes (3-22)
      have been isolated and identified. They belong to two substructural classes of
      miliusanes. One subclass (1-19) was determined to be composed of a gamma-lactone
      spiro-ring system, the opening of which led to the second group of compounds (21
      and 22) containing a tetrahydrofuran ring system. Compounds 1-3, 5, 8, 9, 18, 20,
      and 21 demonstrated significant cytotoxic activity in our cancer cell line panel
      comprising KB, Col-2, LNCaP, Lu-1, MCF-7, and HUVEC. The structures were
      determined by spectroscopic and chemical methods. The structure of miliusate was
      further confirmed by X-ray crystallographic analysis. The absolute
      stereochemistry of miliusanes was established by the Mosher ester method. Forty
      two modified miliusane derivatives were also prepared and evaluated for their
      cytotoxic activities.

PMID- 16420056
TI  - Synthesis and biological activity of isoxazolidinyl polycyclic aromatic
      hydrocarbons: potential DNA intercalators.
AB  - Isoxazolidinyl polycyclic aromatic hydrocarbons (isoxazolidinyl-PAHs) have been
      synthesized in good yields by 1,3-dipolar cycloaddition methodology promoted by
      microwave irradiation. The structures of the obtained cycloadducts have been
      determined by NOE experiments and supported by computational studies at the AM1
      level. The cytotoxicity and antiviral activity of the synthesized compounds have
      been investigated. In particular, compounds 7c and 7e show high levels of
      cytotoxicity on MOLT-3 leukemia cells; 7e exerts a remarkable enhancing activity
      on apoptosis caused by anti-fas antibody addition. Furthermore, compounds 7b and
      8b exhibit specific antiviral effects against the Punta Toro virus.

PMID- 16420057
TI  - (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6
      (trifluoromethyl)pyridin-3- yl]piperazine-1-carboxamide (YM580) as an orally
      potent and peripherally selective nonsteroidal androgen receptor antagonist.
AB  - A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives
      was synthesized and their androgen receptor (AR) antagonist activities and in
      vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that
      compound 33 was a potent AR antagonist, and subsequent optical resolution
      provided (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6
      (trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which
      exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound
      33a decreased the weight of rat ventral prostate in a dose-dependent manner
      (ED(50) = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect,
      comparable to that of surgical castration, without significantly affecting serum
      testosterone levels. Compound 33a is a promising clinical candidate for prostate
      cancer monotherapy.

PMID- 16420058
TI  - Structure-activity relationship studies of novel benzophenones leading to the
      discovery of a potent, next generation HIV nonnucleoside reverse transcriptase
      inhibitor.
AB  - Despite the progress of the past two decades, there is still considerable need
      for safe, efficacious drugs that target human immunodeficiency virus (HIV). This
      is particularly true for the growing number of patients infected with virus
      resistant to currently approved HIV drugs. Our high throughput screening effort
      identified a benzophenone template as a potential nonnucleoside reverse
      transcriptase inhibitor (NNRTI). This manuscript describes our extensive
      exploration of the benzophenone structure-activity relationships, which
      culminated in the identification of several compounds with very potent inhibition
      of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV.
      These potent inhibitors include 70h (GW678248), which has in vitro antiviral
      assay IC(50) values of 0.5 nM against wild-type HIV, 1 nM against the K103N
      mutant associated with clinical resistance to efavirenz, and 0.7 nM against the
      Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has
      also demonstrated relatively low clearance in intravenous pharmacokinetic studies
      in three species, and it is the active component of a drug candidate which has
      progressed to phase 2 clinical studies.

PMID- 16420059
TI  - Wortmannin-C20 conjugates generate wortmannin.
AB  - We report on C20-6-(N-methylamino)hexanoic conjugates of wortmannin featuring a
      tertiary enamine attached to the C20 that inhibit phosphoinositol-3-OH kinase
      (PI3K) by producing wortmannin (Wm) through an intramolecular attack. The
      generation of Wm by these conjugates permits the design of Wm based PI3K
      inhibitors that need not fit into the ATP pocket of PI3K, including Wm conjugates
      of BSA, IgG, or beads. Wm generating WmC20-N(Me)-hexanoate conjugates offer an
      approach to the design of targeted or slow release forms of Wm which may inhibit
      PI3K in tissues more selectively than the parent Wm, a compound which has
      desirable anti-inflammatory and anti-proliferative activities but which also has
      a variety of toxic effects.

PMID- 16420060
TI  - Novel 5alpha-reductase inhibitors: synthesis, structure-activity studies, and
      pharmacokinetic profile of phenoxybenzoylphenyl acetic acids.
AB  - Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been
      synthesized and evaluated for inhibition of rat and human steroid 5alpha
      reductase isozymes 1 and 2. The compounds turned out to be potent and selective
      human type 2 enzyme inhibitors, exhibiting IC(50) values in the nanomolar range.
      The phenylacetic acid derivatives were more potent than the analogous benzoic
      acids. Bromination in the 4-position of the phenoxy moiety led to the strongest
      inhibitor in this class (12; IC(50) = 5 nM), which was equipotent to finasteride.
      Since oral absorption is essential for a potential drug, 12 was further examined.
      In the parallel artificial membrane permeation assay (PAMPA) it turned out to be
      a good permeator, whereas it was a medium permeator in Caco2 cells. After oral
      administration (40 mg/kg) to rats a high bioavailability and a biological half
      life of 5.5 h were observed, making it a promising candidate for clinical
      evaluation.

PMID- 16420061
TI  - Dopamine/serotonin receptor ligands. 10: SAR Studies on azecine-type dopamine
      receptor ligands by functional screening at human cloned D1, D2L, and D5
      receptors with a microplate reader based calcium assay lead to a novel potent
      D1/D5 selective antagonist.
AB  - On the basis of the benz[d]indolo[2,3-g]azecine derivative 1 (LE300), structure
      activity relations were investigated in order to identify the pharmacophore in
      this new class of ligands. Various structural modifications were performed and
      the inhibitory activities at human cloned D(1), D(2L), and D(5) receptors were
      measured by using a simple fluorescence microplate reader based calcium assay.
      Subsequently, the affinities of active compounds were estimated by radioligand
      binding experiments. Deleting one of the aromatic rings as well as replacing it
      by a phenyl moiety abolishes the inhibitory activities almost completely.
      Contraction of the 10-membered central ring decreases them significantly. The
      replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory
      activity, whereas replacing the indole by benzene increases it. Finally, the
      hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more
      active than the lead 1 in the functional calcium assay as well as in radioligand
      displacement experiments.

PMID- 16420063
TI  - Synthesis and biological evaluation of novel phenylcarbazoles as potential
      anticancer agents.
AB  - We here report the synthesis and biological evaluation of new phenylcarbazole
      derivatives designed as potential anticancer agents. Indole and hydroxyindole
      were used to generate three scaffolds that were successively exploited to
      introduce various substituents on the maleimide moiety. The synthesis includes a
      final intramolecular key Heck-type reaction, which was carried out with a
      triflate derivative or with a bromophenyl derivative. Each step was optimized and
      the complete chemical strategy is detailed. Several compounds showed a marked
      cytotoxicity against CEM human leukemia cells with IC(50) values in the 10-100 nM
      range. Precise structure-activity relationships were delineated. Cell cycle
      analysis, topoisomerase I inhibition, and interaction with DNA were evaluated,
      and inhibition of CDK activity was also investigated. Although binding of the
      drugs to DNA likely contributes to the cytotoxic action, the exact molecular
      targets of these molecules remain undiscovered. The efficient chemical routes
      reported here for the design of highly cytotoxic compounds provide novel
      opportunities to identify antitumor agents in the phenylcarbazole series.

PMID- 16420062
TI  - Prodrug forms of N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-gamma
      [psiP(O)(OH)]-glutarate, a potent inhibitor of folylpoly-gamma-glutamate
      synthetase: synthesis and hydrolytic stability.
AB  - Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10
      methyl)pteroyl]glutamate-gamma-[psiP(O)(OH)]-glutarate (1a) were synthesized. H
      phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the
      desired pseudopeptides by Michael addition to alpha-methyleneglutarate esters.
      Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal
      and C-terminal fragments prior to formation of either C-P bond. N-Alkylation of
      the corresponding amides derived from p-(N-methyl)aminobenzoic acid with 2,4
      diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of
      methotrexate and the corresponding gamma-glutamyl conjugate were also synthesized
      using the same strategy. All prodrugs were evaluated in Chinese hamster ovary
      cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of
      methotrexate and the corresponding gamma-glutamyl conjugate were equipotent with
      the parent compounds. Stability of the prodrugs was investigated in both
      phosphate buffer and cell line medium to provide a rationale for the observed
      biological data.

PMID- 16420064
TI  - Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4
      hexadienoic acid hydroxyamides.
AB  - The synthesis of a novel series of potent inhibitors of histone deacetylases is
      described, based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides and their
      derivatives. In vitro IC(50) values down to 40 nM were obtained, and several
      compounds showed inhibition of CEM (human leukemic) cell viability with IC(50) of
      approximately 1.5 microM, comparable to or better than that of suberoylanilide
      hydroxamic acid, an inhibitor of histone deacetylase currently in clinical
      trials.

PMID- 16420065
TI  - Synthesis and in vitro antileukemic activity of some new 1,3
      (oxytetraethylenoxy)cyclotriphosphazene derivatives.
AB  - A new series of 1,3-(oxytetraethylenoxy)cyclotriphosphazene derivatives bearing 2
      chloroethylamine or salicylaldehyde (2-hydroxybenzaldehyde) or its Schiff base
      (after condensation with 2-chloroethylamine) units and having also 2-naphthyl or
      anthraquinone groups as cosubstituents has been synthesized. The in vitro
      cytotoxic activity of these compounds against a panel of four cancer cell lines
      has been studied. Most of the compounds exhibited antiproliferative activity in
      the range of the international criterion for synthetic agents (4 microg/mL)
      against the MOLT4, L 1210, HL-60, and P388 cell lines chosen for testing.

PMID- 16420066
TI  - Correlation of antifungal activity with fungal phospholipase inhibition using a
      series of bisquaternary ammonium salts.
AB  - A series of bisquaternary ammonium salts with a 12-carbon spacer between the
      positive charges were synthesized, and their antifungal activity has been
      investigated. Compounds with butyl, pentyl, and isopentyl headgroups were the
      most potent antifungal agents with MICs in the range of 2.2-5.5 microM against
      both Cryptococcus neoformans and Candida albicans. The antifungal activity of
      these compounds correlated with their inhibition of cryptococcal phospholipase B1
      (PLB1), a newly identified virulence factor. This indicates that the mode of
      action of these compounds may be inhibition of the fungal PLB1 enzyme, further
      validating this enzyme as a target for the development of novel antifungal
      therapies.

PMID- 16420067
TI  - Orally active purine-based inhibitors of the heat shock protein 90.
AB  - Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic
      agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as
      4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble
      and consequently have unacceptably low oral bioavailabilities. We now report that
      water-solubility can be achieved by inserting an amino functionality in the N(9)
      side chain. This results in compounds that are potent, soluble in aqueous media,
      and orally bioavailable. In an HER-2 degradation assay, the highest potency was
      achieved with the neopentylamine 42 (HER-2 IC(50) = 90 nM). In a murine tumor
      xenograft model (using the gastric cancer cell line N87), the H(3)PO(4) salts of
      the amines 38, 39, and 42 induced tumor growth inhibition when administered
      orally at 200 mg/kg/day. The amines 38, 39, and 42 are the first Hsp90 inhibitors
      shown to inhibit tumor growth upon oral dosage.

PMID- 16420068
TI  - Synthesis and in vitro antitumor activity of platinum acetonimine complexes.
AB  - The cis- and trans-dichloro- and diiodo-platinum(II) complexes containing two
      acetonimines (cis- and trans-[PtX(2){HN=C(CH(3))(2)}(2)], 1 and 2 for X = Cl and
      1' and 2' for X = I, respectively) or one acetonimine and one ammine (cis- and
      trans-[PtX(2)(NH(3)){HN=C(CH(3))(2)}], 3 and 4 for X = Cl and 3' and 4' for X =
      I, respectively) have been prepared from platinum-ammine precursors by
      condensation with acetone. Except for the cis-diiodo species, in all other cases
      the presence of a base was required. A crucial role of the ligand trans to the
      ammine undergoing condensation with acetone has been disclosed: the greater the
      trans effect the greater the reactivity. In a panel of human tumor cell lines
      representative of ovarian, colon, lung, and breast cancers, cis complexes 1 and 3
      are less active than cis-DDP (mean IC(50) = 20, 12.5, and 2.8 microM,
      respectively), whereas trans complexes 2 and 4 are more active than trans-DDP
      (mean IC(50) = 10.6, 26, and 164 microM, respectively), thus indicating that
      substitution of acetonimine for one or two ammine ligands determines strikingly
      different effects depending upon the complex geometry.

PMID- 16420069
TI  - Hurricane Katrina: a physician's whirlwind course in disaster psychiatry.

PMID- 16420071
TI  - Efficacy of aripiprazole against hostility in schizophrenia and schizoaffective
      disorder: data from 5 double-blind studies.
AB  - OBJECTIVE: The objective was to determine the effects of aripiprazole on
      hostility. METHOD: A total of 1476 patients diagnosed with DSM-IV schizophrenia
      or schizoaffective disorder were the subjects in 5 short-term, double-blind
      studies comparing aripiprazole with placebo; 3 of these studies also included a
      comparison with haloperidol. The studies were conducted between December 1993 and
      January 2001. The Positive and Negative Syndrome Scale (PANSS) was the principal
      outcome measure in these studies. To determine the effect of aripiprazole on
      hostility, post hoc analyses of the hostility item from the PANSS were conducted
      for the first 4 weeks of treatment. RESULTS: Aripiprazole was superior to placebo
      and not significantly different from haloperidol in reducing hostility.
      CONCLUSION: Aripiprazole is an effective treatment for hostility in patients with
      schizophrenia or schizoaffective disorder.

PMID- 16420070
TI  - The epidemiology of social anxiety disorder in the United States: results from
      the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: To present nationally representative data on 12-month and lifetime
      prevalence, correlates and comorbidity of social anxiety disorder (SAD) among
      adults in the United States as determined by the 2001-2002 National Epidemiologic
      Survey on Alcohol and Related Conditions. DESIGN: Face-to-face survey. SETTING:
      The United States. PARTICIPANTS: Adults (aged 18 and over) residing in households
      and group quarters (N = 43,093). MAIN OUTCOME MEASURES: Prevalence and
      associations of SAD with sociodemographic and psychiatric correlates and Axis I
      and II disorders. RESULTS: The prevalence of 12-month and lifetime DSM-IV SAD was
      2.8% (95% CI = 2.5 to 3.1) and 5.0% (95% CI = 4.6 to 5.4), respectively. Being
      Native American, being young, or having low income increased risk, while being
      male, being of Asian, Hispanic, or black race/ethnicity, or living in urban or
      more populated regions reduced risk. Mean age at onset of SAD was 15.1 years,
      with a mean duration of 16.3 years. Over 80% of individuals with SAD received no
      treatment, and the mean age at first treatment was 27.2 years. Current and
      lifetime SAD were significantly related to other specific psychiatric disorders,
      most notably generalized anxiety, bipolar I, and avoidant and dependent
      personality disorders. The mean number of feared social situations among
      individuals with SAD was 7.0, with the majority reporting anxiety in performance
      situations. CONCLUSIONS: Social anxiety disorder was associated with substantial
      unremitting course and extremely early age at onset. Social anxiety disorder
      often goes untreated, underscoring the need for health care initiatives geared
      toward increasing recognition and treatment. Comprehensive evaluation of patients
      with SAD should include a systematic assessment of comorbid disorders, and novel
      approaches to the treatment of comorbid SAD are needed.

PMID- 16420072
TI  - Clinical characteristics and psychiatric comorbidity in males with exhibitionism.
AB  - BACKGROUND: This study was constructed to detail the demographic and
      phenomenological features of males with exhibitionism. METHOD: Male subjects with
      DSM-IV exhibitionism were administered a semistructured interview to elicit
      demographic data and information on the phenomenology, age at onset, and
      associated features of the disorder. Subjects also underwent structured clinical
      interviews to assess both Axis I and Axis II comorbidities. Data were collected
      from September 2003 to March 2005. RESULTS: Twenty-five males with exhibitionism
      (mean +/- SD age = 35.0 +/-13.1 years [range, 14-68 years]) were studied. The
      majority of subjects were single (60% [N = 15]) and heterosexual (80% [N = 20]).
      The mean +/- SD age at onset for exhibitionism was 23.4 +/-13.1 years. All
      subjects reported urges to expose themselves with little control over these
      urges. Exposing oneself while driving was the most common expression of the
      disorder. Twenty-three (92%) suffered from a current comorbid Axis I disorder
      (major depressive disorder, compulsive sexual behavior, and substance use
      disorders were most common), and 40% (N = 10) suffered from a personality
      disorder. Suicidal thoughts were common (52% [N = 13]), and many (36% [N = 9])
      had been arrested for exhibitionism. CONCLUSION: Exhibitionism appears to be
      associated with high rates of psychiatric comorbidity and impairment. Research is
      needed to optimize patient care for men with this disorder.

PMID- 16420073
TI  - Treatment of the polydipsia-hyponatremia syndrome with urea.
AB  - OBJECTIVE: The polydipsiahyponatremia syndrome is difficult to control in
      patients with severe mental illness, and there is no established effective
      therapeutic approach. We investigate the effect of oral daily intake of large
      amounts of urea to prevent hyponatremic episodes. METHOD: Seven patients were
      treated during 4 to 18 months with urea (0.3-0.9 g/kg/day). Five of these
      patients had schizophrenia. Body weight variation between morning and evening was
      determined before and during the course of therapy in 5 patients. The dose of
      urea was increased if morning serum sodium level (SNa) was lower than 132 mmol/L.
      RESULTS: Urea therapy increased mean +/- SD morning SNa (from 127.5 +/- 3.4
      mmol/L before initiation of urea treatment to 136.5 +/- 2.4 mmol/L during the
      second month of urea treatment; p < .01) and mean +/- SD urine osmolality (from
      86 +/- 39 mOsm/kg H(2)O to 159 +/- 58 mOsm/kg H(2)O; p < .05), probably without
      changes in water intake or urine volume excretion as attested by the level of
      urinary creatinine concentration. Mean +/- SD body weight variation decreased
      from 4.5% +/- 1.0% before initiation of urea treatment to 2.8% +/- 1.0% during
      the second month of urea treatment (p < .05). Two patients stopped urea treatment
      after 1 year and subsequently developed symptomatic hyponatremia. CONCLUSION:
      These preliminary data show that urea appears to be an effective therapeutic
      approach for the polydipsiahyponatremia syndrome.

PMID- 16420074
TI  - Typical and atypical antipsychotics in bipolar depression.
AB  - BACKGROUND: Symptomatic bipolar patients experience more depressive than manic
      symptoms, but fewer studies have been designed for bipolar depression than for
      bipolar mania. Since the antipsychotic agents have been shown to diminish
      depressive symptoms during the treatment of mania, atypical agents are now being
      studied for use in bipolar depression. DATA SOURCES: English-language articles
      published from 1980 through July 2004 and cited in MEDLINE were searched using
      the keywords antipsychotics, typical antipsychotics, atypical antipsychotics,
      bipolar depression, bipolar disorder, manic-depressive illness, placebo, and
      clinical trial. The generic and brand names of individual antipsychotics were
      also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies
      assessing acute or long-term efficacy in bipolar depression presented at major
      scientific meetings were also reviewed. STUDY SELECTION: Use of a depression
      rating scale was required for inclusion of studies of the atypical antipsychotic
      agents in our analysis. DATA SYNTHESIS: Twenty-one randomized trials and 13
      nonrandomized prospective trials were identified. In the only 2 acute, double
      blind, placebo-controlled studies of antipsychotics in bipolar depression, the
      effect size of olanzapine was small (0.32) compared with the effect sizes of
      quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of
      olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively.
      Both olanzapine and quetiapine have been shown to be superior to placebo in the
      acute treatment of bipolar I depression. In addition, olanzapine has been shown
      to be more effective than placebo in delaying relapse into bipolar depression.
      With the exception of a 6-month perphenazine study, there are no other randomized
      studies of typical antipsychotics that support the conclusion that this class of
      medication worsens bipolar depression. CONCLUSION: Emerging data suggest that the
      atypical antipsychotic agents have a role in the acute and long-term treatment of
      bipolar depression. No convincing data support the impression that the typical
      antipsychotic agents worsen bipolar depression.

PMID- 16420075
TI  - QTc interval measurement and metabolic parameters in psychiatric patients taking
      typical or atypical antipsychotic drugs: a preliminary study.
AB  - BACKGROUND: Antipsychotic drugs have been associated with prolongation of the QTc
      interval on the electrocardiogram, and QTc prolongation is, in turn, associated
      with an increased risk of cardiac arrhythmias and sudden death. Antipsychotic
      polypharmacy has been implicated in reduced survival, possibly secondary to
      cardiotoxic effects of antipsychotic medication. Abnormalities of glucose
      homeostasis, which may be more common in individuals with major mood disorders
      and schizophrenia, also affect the QTc interval. METHOD: We performed detailed
      assessment of metabolic parameters in 103 psychiatric out-patients, from across
      the diagnostic spectrum, who had been taking antipsychotic medication (typical,
      atypical, or a combination thereof) for a minimum of 6 months. We measured the
      QTc interval in a subset of these patients (N = 65). RESULTS: Only 2 patients
      (3%) had a prolonged QTc interval. There was a statistical trend (p = .08) toward
      a lower QTc interval in patients receiving antipsychotic polypharmacy. QTc
      interval was associated with age (p = .04) but not with any metabolic parameter.
      CONCLUSION: QTc prolongation in this population is uncommon. There was a
      significant association between increasing age and QTc interval, but cardiac
      repolarization was not related to any metabolic parameter. Further large
      prospective studies of similar patients are needed to confirm these findings.

PMID- 16420076
TI  - Sequential treatment of mood and anxiety disorders.
AB  - OBJECTIVE: Administration of treatments in a sequential order is a common
      practice in clinical medicine, but has received insufficient attention in
      psychiatry. The aim of this review was to survey the literature concerned with a
      sequential use of pharmacotherapy and psychotherapy in mood and anxiety
      disturbances. DATA SOURCES AND STUDY SELECTION: A review of the clinical trials
      in which treatment components were used in a sequential order (i.e.,
      pharmacotherapy followed by psychotherapy, psychotherapy followed by
      pharmacotherapy, one drug treatment following another, or one psychotherapeutic
      technique following another) was performed. Studies were identified by using
      MEDLINE (English language articles published from 1967 to March 2005; keywords:
      sequential treatment, drugs and psychotherapy, combined treatment related to
      depressive disorder, bipolar disorder, depression, mania, anxiety disorders,
      panic disorder, social phobia, obsessive-compulsive disorder, generalized anxiety
      disorder, and posttraumatic stress disorder) and a manual search of the
      literature and Index Medicus for the years 1960 to 2005. DATA SYNTHESIS: In
      unipolar recurrent depression, the sequential use of pharmacotherapy was found to
      reduce relapse rate. In bipolar disorder, the use of psychotherapeutic strategies
      in patients who were already undergoing treatment with mood stabilizers was also
      found to yield clinical benefits. In anxiety disorders, the sequential use of
      pharmacotherapy and psychotherapy was not found to improve long-term outcome.
      CONCLUSION: The sequential treatment of mood and anxiety disorders does not fall
      within the realm of maintenance strategies. It is an intensive, 2-stage approach,
      which is based on the fact that one course of treatment with a specific treatment
      (whether pharmacotherapy or psychotherapy) is unlikely to entail solution to the
      complex array of symptoms of patients with mood and anxiety disorders. The
      sequential model introduces a conceptual shift in current assessment methods.

PMID- 16420078
TI  - Residual symptoms in depressed patients after treatment with fluoxetine or
      reboxetine.
AB  - BACKGROUND: Residual symptoms are common and have a variety of consequences in
      depressed patients who respond to treatment, but seldom have specific residual
      symptoms been assessed. We examined the frequency and severity of residual
      depressive symptoms in 2 studies comparing the selective serotonin reuptake
      inhibitor (SSRI) fluoxetine with the norepinephrine reuptake inhibitor (NRI)
      reboxetine. METHOD: Data from two 8-week, previously published, double-blind,
      random-assignment studies comparing fluoxetine and reboxetine were obtained. Both
      studies included men and women who met DSM-III-R criteria for unipolar
      nonpsychotic major depression. Symptoms were assessed with the 21-item Hamilton
      Rating Scale for Depression (HAM-D). The frequency and severity of residual
      symptoms were determined in the patients who completed treatment and responded
      (had at least 50% improvement on the HAM-D). RESULTS: In study 1, 117 patients
      completed treatment and responded. In study 2, 113 patients completed treatment
      and responded. The most frequent symptoms present after treatment were psychic
      anxiety, lack of interest, somatic anxiety, and depressed mood. No residual
      symptom differed significantly between treatment groups in both samples. Ordinal
      logistic regression, used to control for baseline symptom severity, revealed no
      other differences between drug groups except that decreased libido was
      significantly greater with fluoxetine in study 1 and study 2. Three composite
      scores for residual anxiety, sleep disturbance, and reduced drive did not differ
      between drug groups. CONCLUSION: This study found no differences in residual
      symptoms in depressed patients who responded to treatment with the SSRI
      fluoxetine and the NRI reboxetine, with the exception that the fluoxetine group
      had a greater decrease in sexual interest, a likely side effect of that drug.

PMID- 16420077
TI  - The selective GABA reuptake inhibitor tiagabine for the treatment of generalized
      anxiety disorder: results of a placebo-controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of tiagabine, a selective
      gamma-aminobutyric acid (GABA) reuptake inhibitor, in adults with generalized
      anxiety disorder (GAD). METHOD: This 8-week, randomized, double-blind,
      multicenter, placebo-controlled study enrolled patients with GAD (DSM-IV).
      Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a
      maximum dose of 16 mg/day. Study drug was tapered after week 8 in decrements of 2
      mg every other day. Efficacy assessments included the Hamilton Rating Scale for
      Anxiety (HAM-A) and Sheehan Disability Scale. Adverse events, sexual functioning,
      and change in depressive symptoms were monitored. Data were collected from May
      2003 to January 2004. RESULTS: A total of 266 patients (tiagabine, N = 134;
      placebo, N = 132) were included in safety analyses; 260 patients (tiagabine N =
      130; placebo N = 130) were included in efficacy analyses. Tiagabine reduced
      symptoms of GAD according to the observed case and mixed models repeated-measures
      (MMRM) analyses but not the primary last-observation-carried-forward (LOCF)
      analysis. At final visit, the reduction from baseline in mean HAM-A total score
      was 11.8 for tiagabine, compared with 10.2 for placebo (LOCF analysis, p = .27).
      In a post hoc MMRM analysis, a significant difference in the mean reduction in
      HAM-A total score over the efficacy evaluation period was found, favoring
      tiagabine over placebo (p < .01). Tiagabine had an early onset of effect, as
      shown by significant reduction from baseline in mean HAM-A total score compared
      with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well
      tolerated and not associated with changes in sexual functioning or depressive
      status. Symptoms of a discontinuation syndrome during taper were not observed.
      CONCLUSION: The primary LOCF analysis was negative; however, results from the
      observed case and MMRM analyses suggest that tiagabine may be a useful treatment
      option for adult patients diagnosed with GAD. These findings warrant further
      evaluation in randomized clinical studies.

PMID- 16420079
TI  - Cognitive therapy and exposure in vivo alone and in combination with fluvoxamine
      in obsessive-compulsive disorder: a 5-year follow-up.
AB  - BACKGROUND: Information regarding the long-term effectiveness of the combination
      of pharmacotherapy and cognitive-behavioral therapy (CBT) in the treatment of
      obsessive-compulsive disorder (OCD) is limited. Our study is the first to examine
      the long-term effectiveness of cognitive therapy (CT) and to compare long-term
      effectiveness of CT alone, exposure in vivo with response prevention (ERP) alone,
      and CBT (either CT or ERP) in combination with fluvoxamine in the treatment of
      OCD. METHOD: Of 122 outpatients with primary DSM-III-R-defined OCD originally
      enrolled in 2 randomized controlled trials, 102 patients (45 male/57 female; mean
      +/- SD age = 36.2 +/- 10.7 years; range, 19-64 years) were available to be
      assessed for the presence and severity of OCD and comorbid psychopathology at
      follow-up. Follow-up data were collected from November 1996 to June 1999.
      RESULTS: After 5 years, 54% of the participants no longer met the DSM-III-R
      criteria for OCD. Long-term outcome did not differ between the 3 treatment
      groups. At follow-up, treatment dropouts appeared to have more severe OCD
      complaints compared with treatment completers. Compared with patients receiving
      CT alone, significantly (p < .005) more patients receiving CBT with fluvoxamine
      used antidepressants 5 years later. CONCLUSIONS: This study demonstrates that at
      5-year follow-up (1) prevalence of OCD had declined in all 3 treatment
      conditions, (2) the clinical benefits of all 3 treatment conditions were
      maintained, (3) OCD complaints were more severe for treatment dropouts than for
      treatment completers, and (4) about half of the patients initially treated with
      fluvoxamine continued antidepressant use.

PMID- 16420080
TI  - Naturalistic, retrospective comparison between second-generation antipsychotics
      and depot neuroleptics in patients affected by schizophrenia.
AB  - OBJECTIVE: Data in the literature comparing second-generation antipsychotics
      (SGAs) and depot neuroleptics are scarce. The aim of this retrospective,
      naturalistic study is to examine the relative effectiveness of SGAs and depot
      neuroleptics in 2 matched groups of patients affected by schizophrenia. METHOD:
      Between July 2004 and September 2004, we collected data from 2 groups of 30 DSM
      IV-TR schizophrenia outpatients, matched for a number of demographic and clinical
      characteristics, who received a 2-year treatment with depot neuroleptics or SGAs.
      Treatments were compared through the Clinical Global Impressions-Severity of
      Illness scale (CGI-S), performed on several symptom domains of schizophrenia.
      Other outcomes included 1-and 2-year readmission rates, the number of self
      injuries during the treatment period, and anticholinergic drug prescription,
      considered as an index of extrapyramidal symptoms. RESULTS: Treatment with both
      drug classes produced broadly comparable clinical effects. Clinician-assessed
      effectiveness was similar for SGA and depot recipients, with significant
      decreases over baseline in all CGI-S symptom domain scores. The percentages of
      patients readmitted during the follow-up period were similar among drug groups.
      After 1 year, 6 SGA patients (20%) were readmitted compared with 7 depot patients
      (23%); after 2 years, 9 SGA patients (30%) were rehospitalized compared with 11
      depot patients (37%). Also, no between-group differences were detected with
      respect to the number of self-injuries. Anticholinergic drug prescription was
      significantly less common in SGA patients compared with depot recipients (p =
      .0112). CONCLUSION: These findings confirm at least equal long-term effectiveness
      of depot neuroleptics and SGAs, but a possible advantage for SGAs in decreased
      use of anticholinergic drugs.

PMID- 16420081
TI  - Misdiagnosed patients with bipolar disorder: comorbidities, treatment patterns,
      and direct treatment costs.
AB  - OBJECTIVE: The purpose of this study was to examine comorbidities, treatment
      patterns, and direct treatment costs of patients with bipolar disorder who are
      misdiagnosed with unipolar depression. METHOD: This study is a retrospective
      analysis of data from the MarketScan Commercial Claims and Encounters (CCE)
      database. Logistic regressions and analyses of variance were used to compare the
      misdiagnosis cohort to 3 age- and gender-matched comparison cohorts (recognized
      bipolar, depression, and no psychiatric disorders based on ICD-9-CM criteria)
      during the year 2000. RESULTS: Each cohort had 769 individuals (68.0% female;
      mean age of roughly 42 years). The misdiagnosis cohort had higher rates of
      several psychiatric comorbidities than the depression cohort (e.g., personality
      disorders, alcohol abuse, psychotic disorder) and the bipolar cohort (e.g.,
      generalized anxiety disorder, panic) but a lower rate of psychotic disorders than
      the bipolar cohort (p < .05). Compared with the bipolar cohort, the misdiagnosis
      cohort was more likely to receive antidepressants, but less likely to receive
      anticonvulsants, antipsychotics, or lithium (all p < .001). Antidepressant rates
      were similar among the misdiagnosis and depression cohorts. Group differences
      were found in mean annual costs for anticonvulsants, antipsychotics, lithium,
      antidepressants, and total treatment costs: bipolar (USD $442, $310, $67, $497,
      $8600); misdiagnosis (USD $221, $185, $20, $704, $8761); depression (USD $70,
      $74, $5, $657, $7288). CONCLUSION: Misdiagnosed bipolar patients received
      inappropriate and costly treatment regimens involving overuse of antidepressants
      and underuse of potentially effective medications. Patterns of psychiatric
      comorbidity suggest one possible strategy for improving recognition of bipolar
      disorder among patients presenting with depressive symptoms. Patients who present
      with the observed pattern of comorbidities may benefit from additional screening
      for bipolar disorder. It is recommended that steps be taken to minimize
      misdiagnosis in clinical settings.

PMID- 16420082
TI  - Safety and efficacy of escitalopram in the long-term treatment of generalized
      anxiety disorder.
AB  - INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic disorder that
      requires long-term treatment. Escitalopram has previously been shown to be
      effective and well tolerated in the acute treatment of GAD. METHOD: Three 8-week,
      double-blind, placebo-controlled trials of nearly identical design were conducted
      of escitalopram in moderate-to-severe GAD (DSM-IV criteria). Patients completing
      these trials were given the option of entering a 24-week, open-label, flexible
      dose trial of escitalopram (10-20 mg/day). Data were collected from September 20,
      2000, to August 15, 2002. RESULTS: Two hundred ninety-nine (56.8%) of 526
      patients completed 24 weeks of open-label treatment. The mean Hamilton Rating
      Scale for Anxiety (HAM-A) score at baseline of open-label treatment was 13.1.
      Long-term escitalopram treatment led to continuing improvement on all anxiety and
      quality-of-life (QOL) scores. Of those completing 24 weeks of treatment, 92.0%
      were responders (Clinical Global Impressions-Improvement scale score < or = 2),
      and the mean HAM-A score in the completed analysis was 6.9; using the last
      observation carried forward (LOCF), 75.9% were responders, and the mean HAM-A
      score in the LOCF analysis was 9.2 at endpoint. Insufficient therapeutic response
      and adverse events led to withdrawal of 4.2% and 9.9% of patients, respectively.
      Mean increase in weight from baseline was 3.0 lb. No clinically notable changes
      in mean laboratory, vital sign, or electrocardiographic values were observed.
      CONCLUSION: These results support the long-term tolerability and effectiveness of
      escitalopram in the treatment of GAD.

PMID- 16420083
TI  - Variables associated with alcohol, drug, and daily smoking cessation in patients
      with severe mental illnesses.
AB  - BACKGROUND: Co-occurrence of substance use disorders and severe mental illnesses
      (SMIs) is a major U.S. public health issue, although the role of tobacco is
      usually neglected. This study explored variables associated with alcohol, drug,
      and smoking cessation in a naturalistic setting. METHOD: Logistic regression was
      used to study variables associated with cessation of alcohol and drug use
      disorder and daily smoking in 560 SMI inpatients and outpatients from central
      Kentucky facilities. Patients with a lifetime history of alcohol or drug use
      disorder were considered to be in cessation if they had not suffered from abuse
      or dependence during the last year. Alcohol and drug use disorder diagnoses were
      determined using the Clinician Rating of Alcohol and Drug Use Disorder. Patients
      were recruited from July 2000 to March 2003. RESULTS: The cessation rates for
      alcohol and drug use disorders were, respectively, 44% (95% CI = 39% to 49%) and
      46% (CI = 40% to 51%); these were higher than the daily cigarette smoking
      cessation rate of 10% (CI = 7% to 13%). Drug use disorders (p < or = .02),
      outpatient status (p < .001), and having a medical complication of obesity
      (diabetes mellitus, hypertension, or hyperlipidemia; p < .001) were significantly
      associated with alcohol cessation. Alcohol use disorder (p < .001), starting
      treatment with psychiatric medications after 33 years of age (p < .001), taking
      these medications for 14 years or more (p = .02), schizophrenia diagnosis (p <
      .001), outpatient status (p = .03), and obesity (p = .04) were significantly
      associated with drug cessation. Cessation of daily smoking was associated with
      hypertension (p = .02), late start of treatment with psychiatric medications (>
      33 years old; p = .01), and lack of lifetime drug abuse (p < .001). CONCLUSIONS:
      These results are limited by the cross-sectional and naturalistic design but
      suggest that public health experts, researchers, and clinicians need to mindfully
      address smoking cessation in patients with SMIs. Clinicians may want to consider
      that medical illnesses may motivate patients with SMIs to stop substance abuse
      and that patients with SMIs who abuse both alcohol and drugs rarely stop abusing
      just one of them.

PMID- 16420084
TI  - Suicidal ideation and attempts in bipolar I and II disorders.
AB  - OBJECTIVE: Few studies have investigated the prevalence of and risk factors for
      suicidal ideation and attempts among representative samples of psychiatric
      patients with bipolar I and II disorders. METHOD: In the Jorvi Bipolar Study
      (JoBS), psychiatric inpatients and outpatients were screened for bipolar
      disorders with the Mood Disorder Questionnaire from January 1, 2002, to February
      28, 2003. According to Structured Clinical Interviews for DSM-IV Axis I and II
      Disorders, 191 patients were diagnosed with bipolar disorders (bipolar I, N = 90;
      bipolar II, N = 101). Suicidal ideation was measured using the Scale for Suicidal
      Ideation. Prevalence of and risk factors for ideation and attempts were
      investigated. RESULTS: During the current episode, 39 (20%) of the patients had
      attempted suicide and 116 (61%) had suicidal ideation; all attempters also
      reported ideation. During their lifetime, 80% of patients (N = 152) had had
      suicidal behavior and 51% (N = 98) had attempted suicide. In nominal regression
      models, severity of depressive episode and hopelessness were independent risk
      factors for suicidal ideation, and hopelessness, comorbid personality disorder,
      and previous suicide attempt were independent risk factors for suicide attempts.
      There were no differences in prevalence of suicidal behavior between bipolar I
      and II disorder; the risk factors were overlapping but not identical. CONCLUSION:
      Over their lifetime, the vast majority (80%) of psychiatric patients with bipolar
      disorders have either suicidal ideation or ideation plus suicide attempts.
      Depression and hopelessness, comorbidity, and preceding suicidal behavior are key
      indicators of risk. The prevalence of suicidal behavior in bipolar I and II
      disorders is similar, but the risk factors for it may differ somewhat between the
      two.

PMID- 16420085
TI  - Undiagnosed hyperglycemia in patients treated with atypical antipsychotics.
AB  - BACKGROUND: The use of atypical antipsychotics has been associated with
      abnormalities of glucose metabolism in patients with schizophrenia. This study
      was designed to determine the proportion of undiagnosed hyperglycemia in patients
      receiving a broad range of atypical antipsychotics. METHOD: All outpatients
      treated at an urban Veterans Affairs medical center who received a prescription
      for clozapine, risperidone, olanzapine, quetiapine, or ziprasidone were
      identified, and an attempt was made to obtain a fasting plasma glucose (FPG)
      test. Testing took place October 2000 to November 2002. Patients previously
      diagnosed as diabetic were excluded. RESULTS: Of the 647 patients who received
      antipsychotic prescriptions and were not diagnosed as diabetic, 494 (76.4%) had a
      random glucose result, while 153 (23.6%) had an FPG result. Within the FPG group,
      107 (69.9%) had a normal FPG level, while 46 (30.1%) had an abnormally elevated
      FPG. There were no differences between these 2 groups in terms of race/ethnicity,
      age, body mass index, or comorbid diagnoses. However, significantly more patients
      receiving clozapine were found to have occult hyperglycemia (p = .001); no
      significant differences in the percentage of patients with FPG levels > or = 100
      mg/dL and those with FPG levels < 100 mg/dL were observed for any of the other
      medications. CONCLUSION: Hyperglycemia is common in patients treated with
      atypical antipsychotics and thought to be euglycemic. Screening for elevated FPG
      is indicated for patients receiving atypical antipsychotics.

PMID- 16420088
TI  - Sexual function and dysfunction during treatment with psychotropic medications.

PMID- 16420086
TI  - Long-term weight gain in patients treated with open-label olanzapine in
      combination with fluoxetine for major depressive disorder.
AB  - OBJECTIVE: Patients with major depressive disorder (MDD) treated with olanzapine
      in combination with fluoxetine (OFC) demonstrate robust improvement in their
      depressive symptoms. Treatment with olanzapine may impact a patient's weight;
      thus, long-term weight gain and potential predictors (e.g., age and gender) and
      correlates (e.g., cholesterol and glucose levels) of weight gain were
      investigated in OFC-treated patients with MDD. METHOD: Outpatients who met the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic
      criteria for MDD were included (N = 549) in the current analyses of this 76-week,
      open-label study (February 2000 to July 2002). Maximum, endpoint, and potentially
      clinically significant (PCS; > or = 7% increase from baseline) weight gain; time
      to PCS weight gain; and predictors and correlates of weight change were assessed.
      Patients were treated once daily with oral olanzapine (6, 12, or 18 mg) plus
      fluoxetine (25, 50, or 75 mg) capsules. Statistical significance for all tests
      was based upon p < or = .05. RESULTS: Mean baseline-to-endpoint weight change was
      5.6 +/- 6.6 kg (12.3 +/- 14.6 lb). Weight gain plateaued by 52 weeks. Fifty-six
      percent of patients met criteria for PCS weight gain by 76 weeks, and the median
      time to PCS weight gain was 16 weeks. Low baseline body mass index (BMI), female
      gender, younger age, and increased fluoxetine dose were predictors of weight
      gain; olanzapine dose was not. Patients with early (< or = 6 weeks) rapid PCS
      weight gain were 4.6 times more likely to gain substantial (> or = 15%) weight
      long-term (weeks 7-76). Changes to endpoint in total cholesterol and systolic
      blood pressure values were positively correlated with weight change. CONCLUSION:
      Long-term (76 weeks) OFC treatment may lead to a large percentage (56%) of
      patients meeting criteria for PCS weight gain (> or = 7%). The risk of weight
      gain may be significantly increased for OFC-treated patients who have a low BMI
      or who are female, younger, or taking high-dose fluoxetine. It is important that
      prescribers balance the risk of weight gain with the benefit of treatment for
      individual patients with depression.

PMID- 16420087
TI  - Untangling depression and anxiety: clinical challenges.

PMID- 16420089
TI  - Clozapine-induced pericarditis, pericardial tamponade, polyserositis, and rash.

PMID- 16420091
TI  - Applying parsimony to "An African patient with ziprasidone intolerance".

PMID- 16420092
TI  - Initial evidence of the beneficial effects of glutamate-modulating agents in the
      treatment of self-injurious behavior associated with borderline personality
      disorder.

PMID- 16420093
TI  - Orally disintegrating antipsychotics may promote compliance and adherence in
      patients with schizophrenia.

PMID- 16420094
TI  - Reexamining paroxetine and cognitive-behavioral therapy in postpartum depression
      and anxiety.

PMID- 16420097
TI  - The mental health risks of adolescent cannabis use.

PMID- 16420098
TI  - Bioethical Implications of Globalization: an international consortium project of
      the European Commission.

PMID- 16420099
TI  - Screening the United States blood supply for West Nile Virus: a question of
      blood, dollars, and sense.

PMID- 16420100
TI  - A multistate model for the fluorescence response of R-phycoerythrin.
AB  - Although strong fluorescence makes the R-phycoerythrin (R-PE) proteins
      increasingly useful in biological and clinical assays, they are subject to
      nonlinear effects including transitions to collective dark states and
      photodegradation, which complicate quantitative applications. We report
      measurements of R-PE fluorescence intensity as a function of incident power,
      duration of illumination and temperature. Emission intensity in the band at 570
      nm is proportional to incident power for low power levels. At higher incident
      power, the emission at 570 nm is smaller than expected from a linear dependence
      on power. We propose that R-PE undergoes both reversible emission cessation on a
      millisecond time scale attributed to transitions to a collective dark state, and
      irreversible photodegradation on a time scale of minutes. Singlet oxygen
      scavengers such as dithiothreitol and n-propyl gallate have protective effects
      against the latter effect but not the former. Electrophoretic analysis of
      irradiated solutions of R-PE indicates that significant noncovalent aggregation
      is correlated with photodegradation. A multistate model based on fluorescence
      measurements and geometric analysis is proposed for the fluorophores in R-PE. The
      phycobilin fluorophores are partitioned into three groups: the phycourobilins
      (PUB) absorbing at 490 nm, one group of phycoerythobilins (PEB) absorbing at 530
      nm (PEB-530) and another group of PEB absorbing at 560 nm (PEB-560). The two
      processes that result in the loss of fluorescence intensity are most likely
      associated with the PEB-560 group.

PMID- 16420101
TI  - A theoretical elucidation on the solvent-dependent photosensitive behaviors of
      C60.
AB  - In this paper, the solvent-dependent photosensitive behaviors of fullerene
      (C(60)) were investigated in polar and nonpolar solvents by time-dependent
      density functional theory (TD-DFT) calculation. Based on the calculated
      physicochemical parameters on triplet state, it is revealed that excited-state
      C(60) only generates (1)O(2) via energy transfer in benzene, but can give birth
      to O(2)(.-) and (1)O(2) in water via energy transfer and electron transfer,
      respectively. Considering the fact that electron transfer is more favorable
      compared with energy transfer in polar biological systems, especially with the
      presence of electron donors, the O(2)(.-)-generating process will get predominant
      in physiological systems. These results account well for the experimental
      observations that O(2)(.-) and (.)OH are primarily responsible for the
      photoinduced DNA cleavage by C(60) under physiological conditions, whereas
      (1)O(2) plays a critical role in nonpolar solvents.

PMID- 16420102
TI  - Photochemical internalization of transgenes controlled by the heat-shock protein
      70 promoter.
AB  - Photochemical internalization (PCI) is a targeting technique that facilitates
      endosomal escape of macromolecules, such as transgenes, in response to
      photochemical treatment with endosome/lysosome-localized photosensitizers, such
      as disulfonated meso-tetraphenylporphine (TPPS(2a)). In gene therapy this leads
      to enhanced transgene expression. Moreover, photochemical treatment generally
      activates transcription of stress-response genes, such as heat-shock proteins
      (HSPs), via stimulation of corresponding promoters. Therefore, we used HSP70
      (HSPp; a promoter from the HSP family gene) and investigated whether the PCI
      stimulus could also activate HSPp and thereby stimulate transcription
      (expression) of the HSPp-controlled transgene internalized via PCI. Using human
      colorectal carcinoma and hepatoma cell lines in vitro, we showed that TPPS(2a)
      based photochemical treatment enhances expression of cellular HSP70, which
      correlated with a photochemically enhanced expression (approximately 2-fold, at
      PCI-optimal doses) of the HSPp-controlled transgene integrated in the genome.
      Furthermore, PCI enhanced expression of the HSPp-controlled episomal transgene
      delivered as a plasmid. However, in plasmid-based transfection, PCI-mediated
      enhancement with HSPp did not exceed the enhancement achieved with the
      constitutive active CMV promoter. In conclusion, we demonstrated that the PCI
      relevant treatment initiates HSP70 response and that the HSP70 promoter can be
      used in combination with PCI, leading to PCI-enhanced expression of the HSPp
      controlled transgene.

PMID- 16420104
TI  - Antiretroviral therapy and dyslipidaemia: unlocking the code.

PMID- 16420105
TI  - A 30-month evaluation of the effects on the cost and utilization of proton pump
      inhibitors from adding omeprazole OTC to drug benefit coverage in a state
      employee health plan.
AB  - OBJECTIVE: On March 1, 2004, the state employee health plan began covering
      omeprazole OTC (over the counter) at a $5 copayment. Reimbursement to pharmacy
      providers for omeprazole OTC increased by $10.50 per claim, from $2.50 to a $13
      dispensing fee. Initially, neither generic omeprazole prescription (Rx) nor brand
      omeprazole Rx was covered because omeprazole OTC was available in the same
      strength as the Rx products at a lower cost, but an omeprazole OTC shortage
      necessitated coverage of generic omeprazole Rx at a $10 copay. The objective of
      this study was to evaluate the long-term financial impact of a drug benefit
      policy change on a mid-size state employee health plan and its beneficiaries
      associated with the addition to coverage of omeprazole OTC. METHODS: The pharmacy
      claims database for the employee benefits division (EBD) was used to examine
      utilization and cost data for beneficiaries who received proton pump inhibitors
      (PPIs). Pharmacy claims for the 30-month period for dates of service from
      December 1, 2002, through May 31, 2005, were extracted from the database,
      yielding a preperiod of 15 months and a postpolicy change period of 15 months.
      RESULTS: In the 15-month postperiod, the number of PPI claims per member per
      month (PMPM) decreased by 3.9%, but the days of PPI therapy PMPM increased from
      1.71 to 1.82 (6.4%). Price as measured by the allowed charge per day of drug
      therapy decreased from $4.25 to $2.74 (35.6%) despite an increase of $1.89 (76%)
      in the average dispensing paid per PPI claim to pharmacies, from $2.49 to $4.38.
      The average beneficiary copayment decreased by $0.50 (2.0%) per PPI claim, from
      $25.06 in the preperiod to $24.56 per claim in the postperiod. Therefore, the net
      heath plan cost for PPIs decreased by $2.20 PMPM (37.6%) during the 15-month
      postperiod, from $5.84 to $3.64 PMPM, producing savings of $4,207,350, or
      annualized savings of $3,365,880, in this employee benefit plan of 127,495
      members. CONCLUSION: A change in policy to include coverage of omeprazole OTC and
      an increase in pharmacy reimbursement for omeprazole OTC resulted in 38% net
      savings to a state employee health plan. The large difference in drug acquisition
      cost between omeprazole OTC and the other Rx-only PPIs made it possible to
      implement a program intervention that provided financial benefit to pharmacists,
      beneficiaries, and the drug plan sponsor despite a 6% increase in PPI
      utilization.

PMID- 16420106
TI  - Analysis of the effectiveness and cost benefit of leukotriene modifiers in adults
      with asthma in the Ohio Medicaid population.
AB  - OBJECTIVE: The objectives of this research were to (1) determine the association
      of the use of leukotriene modifiers (LMs) with 3 clinical outcome measures that
      can serve as proxy measures of effectiveness: subsequent emergency room visits,
      hospitalizations, and steroid bursts, and (2) estimate whether LM use compared
      with nonuse is cost beneficial from a Medicaid payer perspective. METHODS: This
      was a retrospective, longitudinal study of asthma patients in the fee-for-service
      Ohio Medicaid program. The study population included 5,541 adult patients who
      were identified as having a claim containing an International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for asthma (code
      493.xx, excluding 493.2x) in 2001. Logistic regression, controlling for selection
      bias through the use of propensity scores, was used to determine the association
      of LM use on 3 outcome measures: emergency room visits, hospitalizations, and
      steroid bursts. An oral steroid burst was defined as a pharmacy claim for oral
      prednisone in the date range from 1 day before to 3 days after an office visit
      that has an ICD-9-CM code for asthma. A cost-benefit analysis was also performed.
      RESULTS: During the prestudy period, the LM users had higher total medical costs
      of $72.06 per patient per month (PPPM, $170.60 vs. $98.54, P <0.001). During the
      outcome period, there was no significant association between LM use and emergency
      room visits (odds ratio [OR] 1.09; 95% confidence interval [CI], 0.84-1.38),
      hospitalizations (OR 1.02; 95% CI, 0.66-1.59), or steroid bursts (OR 1.30; 95%
      CI, 0.89-1.90). Because LM use was not more effective than nonuse and is more
      expensive than nonuse, a situation of dominance prevails. The mean cost
      difference in the 3 primary outcome measures between LM users and nonusers was
      $1.63 PPPM ($34.93 vs. $33.30, P=0.019). CONCLUSION: In this study of adult
      Medicaid asthma patients, users of LMs did not have greater asthma control as
      measured by emergency room visits, hospitalizations, or steroid bursts. In this
      cohort of adult asthma patients with at least 1 asthma medication, there does not
      appear to be any cost offsets to the Ohio Medicaid program associated with the
      use of LMs. The use of LMs was associated with higher total costs for asthma
      care.

PMID- 16420107
TI  - Higher costs and therapeutic factors associated with adherence to NCQA HEDIS
      antidepressant medication management measures: analysis of administrative claims.
AB  - OBJECTIVE: To determine if the type of antidepressant drug is related to
      adherence to National Committee for Quality Assurance (NCQA) Antidepressant
      Medication Management (AMM) quality measures and to assess the 6-month health
      care costs among newly diagnosed depressed patients. METHODS: The MarketScan
      Commercial Claims and Encounter database for medical and pharmacy claims from
      January 2001 to September 2004 was used to assess adherence to the 3 AMM quality
      of-care measures. AMM measures include (a) acute phase, the percentage of
      eligible members who remained on antidepressant medication continuously for 3
      months after the initial diagnosis as determined by at least 84 days supply of
      antidepressant drugs during the first 114 days following receipt of the index
      antidepressant; (b) continuation phase, the percentage of eligible members who
      remained on antidepressant medication continuously for the 6 months after the
      initial diagnosis as determined by at least 180 days supply of antidepressants
      during the first 214 days following receipt of the index antidepressant; and (c)
      practitioner contacts, the percentage of members who received at least 3 follow
      up office visits or telephone contacts with health care providers, including at
      least 1 contact with a practitioner licensed to prescribe (may not necessarily be
      the prescriber of the antidepressant). A fourth measure, overall adherence, was
      added, if all 3 AMM measures were met. Multivariate regression models determined
      demographic, clinical (such as receipt of mental health specialty care, the
      Charlson Comorbidity Index score, and co-occurring bipolar or schizophrenia), and
      therapy-related factors associated with outcomes of adherence and costs (paid
      amounts for insurance-reimbursable health care services for inpatient admissions,
      emergency department services, outpatient services, and outpatient prescription
      drugs). Health care expenditures (both total and mental-health-specific costs)
      were measured for each patient for 6 months following the date of service for the
      index antidepressant. RESULTS: A total of 60,386 adult patients (10.7%) of
      562,898 patients with a depression diagnosis met NCQA inclusion criteria in the
      AMM Technical Specifications (e.g., aged 18 years or older, newly diagnosed with
      depression and initiating antidepressant therapy, 365 days of continuous
      enrollment; patients were excluded if there were missing data on dose or quantity
      of index drug in pharmacy claims or initiated therapy on 2 or more
      antidepressants as the index medication, exclusion criteria not in the AMM
      Technical Specifications). Only 19% of patients achieved overall adherence. Rates
      for the 3 AMM measures were 39% for practitioner contacts, 65% for acute phase,
      and 44% for continuation phase. Receipt of mental health specialty care was the
      only factor that was positively associated with greater adherence on all 4
      measures (overall measure: odds ratio [OR]=3.895, 95% confidence interval [CI],
      3.72-4.07; acute OR=1.38, 95% CI, 1.33-1.43; continuation OR=1.46, 95% CI, 1.41
      1.51; contacts OR=5.83, 95% CI, 5.62-6.06). Most patients were initiated on
      selective serotonin reuptake inhibitors (SSRIs, 69.5%), followed by venlafaxine
      (21.4%), tricyclic antidepressants (TCAs, 21.4%), bupropion (11.0%), and other
      antidepressants (e.g., mirtazapine, nefazadone, trazadone; 7.2%). Before
      adjustment for confounding factors, patients initiated on venlafaxine, TCAs, or
      other antidepressants had higher rates of adherence on the overall performance
      measure versus initiators on SSRIs, but the absolute differences were relatively
      small: 21.4% for venlafaxine and TCAs and 23.1% for other antidepressants versus
      18.5% for SSRIs (P <0.001). Patients initiated on venlafaxine, TCAs, or other
      antidepressants were also more likely to receive care from a mental health
      specialist, 16.8%, 15.0%, and 54.8%, respectively, compared with SSRIs (13.0%,
      all P <0.001). Regression analysis showed that only venlafaxine had a higher OR
      (1.13; 95% CI, 1.05-1.22) compared with SSRIs for adherence on the overall
      measure. Initiating dose level was in the target range for 70.0% of all patients
      (24.9% were below target dose and 5.2% above target dose), and adherent patients
      on all 3 AMM measures were less likely than nonadherent patients (70.4% vs.
      68.4%, P <0.001) to be initiated in the target dose range. After multivariate
      adjustment, the initiating dose (target vs. high) was a significant factor in
      explaining adherence to the overall measure (OR=1.26; 95% CI, 1.16- 1.37).
      Adherent patients had 6-month median unadjusted total health care expenses that
      were nearly 2 times higher compared with nonadherent patients ($5,169 vs. $2,734)
      and mental health expenditures that were nearly 3 times higher ($1,922 vs. $677).
      After adjustment, adherent patients compared with nonadherent patients incurred
      an additional $644 in mental health expenditures and $806 in overall health care
      expenditures in the 6 months following initiation of antidepressant therapy.
      CONCLUSIONS: Only 19% of depressed patients initiated on antidepressants met all
      3 criteria set forth in the NCQA Health Plan Employer Data and Information Set
      (HEDIS) AMM quality-of-care performance measures. Receipt of mental health
      specialty care was the single factor most strongly associated with quality
      treatment by these measures. Type and dosage level of initial antidepressant was
      associated with adherence to the NCQA HEDIS AMM measures, but the absolute
      difference in rates of adherence were relatively small among types of
      antidepressants. Costs were higher for guideline-adherent individuals in the 6
      months following treatment initiation. These analyses were limited to
      administrative claims that lack indicators of depression disease severity.

PMID- 16420108
TI  - A comparison of clinical practice guidelines in the initial pharmacological
      management of new-onset epilepsy in adults.
AB  - OBJECTIVE: Clinical practice guidelines (CPGs) are intended not only to provide
      supportive information for health care providers but also to act as a guide for
      health care policy decisions. However, extant CPGs do not always reach the same
      conclusions. The objective of this study was to compare recommendations for
      initial pharmacological treatment of new-onset epilepsy in adults as stated
      within published CPGs. METHODS: We performed a systematic review of CPGs, which
      were published by prominent national organizations between January 2000 and June
      2005, regarding the initial pharmacological treatment of epilepsy in adults.
      RESULTS: Five CPGs and 1 evidence report were identified that focus on
      pharmaceutical management in epilepsy. The 3 guidelines most relevant to the
      question of new-onset epilepsy treatment in adults were developed by the American
      Academy of Neurology (AAN), Scottish Intercollegiate Guidelines Network (SIGN),
      and National Institute for Health and Clinical Excellence (NICE). AAN recommends
      the use of both recently introduced antiepileptic drugs (AEDs: gabapentin,
      lamotrigine, topiramate, and oxcarbazepine) and standard agents (carbamazepine,
      phenytoin, valproic acid/divalproex, and phenobarbital) in newly diagnosed
      epilepsy, i.e., a nontiered approach. Alternatively, NICE recommends using newer
      AEDs (lamotrigine, topiramate, and oxcarbazepine) only in patients who derive no
      benefit from older agents--a tiered approach. SIGN notes that all AEDs licensed
      for monotherapy have similar efficacy in newly diagnosed epilepsy--a
      recommendation for a nontiered approach. The newer AEDs (lamotrigine and
      oxcarbazepine) are recommended as first-line initial treatment as are standard
      agents (carbamazepine and valproic acid/divalproex). The NICE guideline includes
      economic and quality-of-life evidence in their recommendations while AAN and SIGN
      do not. In these regards, current data fails to show superiority for newer
      agents. CONCLUSION: In the past 5 years, several CPGs have been published in
      epilepsy management. Only 3 guidelines have explicit recommendations for initial
      pharmacological treatment of adults with epilepsy. With some variation regarding
      which medications are recommended from each group, all CPGs promote standard and
      newer AEDs as having similar clinical efficacy. Until efficacy, quality of life,
      or cost data for the newer agents demonstrates a superior outcome, older AEDs
      remain viable options as first-line for monotherapy in newly diagnosed patients
      and may provide cost benefits over newer agents.

PMID- 16420109
TI  - Impact of a clinical pharmacy consult service on guideline adherence and
      management of gabapentin for neuropathic pain.
AB  - OBJECTIVE: Our objectives were to (1) determine whether a computerized clinical
      pharmacy approval and follow-up consult process for ordering new prescriptions
      for gabapentin for the treatment of neuropathic pain decreased the number of
      patients without documented treatment benefit while increasing follow-up and
      documentation of effectiveness, and (2) describe gabapentin use patterns at a
      Veterans Affairs (VA) Medical Center, including the use of first-line therapies
      prior to gabapentin therapy for neuropathic pain. METHODS: The clinical pharmacy
      intervention included review of (1) the indication for gabapentin; (2) the
      required use and failure or contraindication of 3 first-line therapies:
      nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants (TCAs),
      and capsaicin cream; (3) the initial pain assessment; and (4) patient follow-up
      in 4 to 6 weeks, with repeat pain assessment. A retrospective chart review was
      performed for all patients who received a new prescription for gabapentin from
      October 2002 to April 2003 at the Portland VA Medical Center (PVAMC). The
      outcomes of interest for the provider group versus the clinical pharmacy managed
      group included follow-up at 6 weeks or less versus follow-up at more than 6
      weeks, documentation of treatment benefit, how many of the 3 first-line therapies
      were tried before gabapentin, and whether the gabapentin therapy was
      discontinued. RESULTS: There were 237 patients who received a new prescription
      for gabapentin between October 2002 and April 2003. Of these gabapentin
      prescriptions, 61% (n=144) were prescribed for neuropathic pain. Of the new
      gabapentin prescriptions for neuropathic pain, 61% (n=88) were made from approved
      clinical pharmacy consults, 38% (n=54) were ordered without a clinical pharmacy
      consult, and 1% (n=2) were not included because the patient received the drug
      despite denial by the clinical pharmacy consult. The rate of follow-up to assess
      documentation of benefit of therapy with gabapentin was 87% (n=62) in the
      clinical pharmacy consult group compared with 51% (n=27) in the provider-managed
      group (chi2=18.07, P<0.001). Of the patients who were assessed by follow-up, 89%
      (n=55) of the clinical pharmacy consult group received follow-up within 6 weeks
      versus 52% (n=14) of the provider-managed group (chi2=12.63, P <0.001). Compared
      with the patients managed by clinical pharmacists, 43% (n=23) of the gabapentin
      patients in the provider-managed group had no evidence of prior use of any of the
      3 agents required by the gabapentin neuropathic pain guideline, 55% (n=29) had
      evidence of prior use of 1 or 2 first-line agents, and only 2% (n=1) had evidence
      of prior use of all 3 required first-line agents, versus 100% (n=71) of the
      patients managed by clinical pharmacy consult. There was no difference in the
      rate of continuation of gabapentin therapy in the group of patients who received
      clinical pharmacy consults (65%) compared with the provider-managed group (68%,
      chi2=0.11, P=0.718). Of the 148 pharmacy consults for new gabapentin
      prescriptions that were completed during the 7-month period from October 2002
      through April 2003, 60 (40%) were denied, which resulted in the lack of
      gabapentin use in these 60 patients. CONCLUSIONS: A clinical pharmacy
      intervention as part of the management of a treatment guideline for appropriate
      gabapentin use promotes documentation of drug therapy effectiveness in
      neuropathic pain and prevention of gabapentin use prior to a trial with
      alternative first-line therapies.

PMID- 16420111
TI  - Referral bias and other perspectives on the HEDIS measuring stick for quality of
      care in depression treatment.

PMID- 16420110
TI  - A pilot study of home treatment of deep vein thrombosis with subcutaneous once
      daily enoxaparin plus warfarin.
AB  - OBJECTIVE: To evaluate patient satisfaction, effectiveness, and safety of at-home
      treatment of acute deep vein thrombosis (DVT) with subcutaneous enoxaparin dosed
      at 1.5 mg/kg once daily plus oral warfarin. METHODS: Patients with acute DVT and
      no more than 1 previous episode of DVT received enoxaparin plus oral warfarin
      until their international normalized ratio (INR) was >2 on 2 consecutive days.
      Patients were recruited between November 2000 and June 2003, and a home-care
      nurse visited the patient daily to administer the enoxaparin and to perform a
      fingerstick INR test. Patients received warfarin at doses adjusted to maintain an
      INR in the range of 2 to 3. Efficacy and safety were assessed daily by a home
      care nurse and then by telephone interview conducted by a pharmacist at 14, 30,
      and 90 days during follow-up. Patient satisfaction with treatment was assessed by
      a verbal questionnaire. RESULTS: There were 52 patients enrolled. The mean
      duration of enoxaparin home treatment was 4.5 days, and the mean INR on
      discontinuation of enoxaparin was 2.73. Most patients (84.6%) had INRs within the
      desired therapeutic range (INR value 2-3); no patient had a subtherapeutic INR.
      There were no symptoms of recurrent venous thromboembolism reported. Major
      bleeding occurred 7 days after discontinuation of enoxaparin in one patient with
      impending surgery for removal of a uterine tumor. There were 2 cases of minor
      bleeding. The patient satisfaction questionnaire revealed that patients
      considered home treatment to be acceptable. The average cost savings was $2,925
      per patient compared with typical inpatient treatment with unfractionated
      heparin. CONCLUSION: The results of this pilot study suggest that home treatment
      with initial once-daily enoxaparin in conjunction with long-term oral warfarin is
      a safe and effective alternative to inpatient therapy with once-daily enoxaparin
      or unfractionated heparin for select patients with acute DVT. Cost savings are
      derived from the substitution of inpatient care with home care.

PMID- 16420112
TI  - Chasing quality--clinical practice guidelines and HEDIS measures of asthma and
      depression therapy management.

PMID- 16420113
TI  - Asthma disease management--evidence-based medicine must be dynamic.

PMID- 16420114
TI  - The development of ethnic identity during adolescence.
AB  - The development of ethnic identity is a critical facet of adolescence,
      particularly for adolescents of color. In order to examine the developmental
      trajectory of ethnic identity, African American, Latino American, and European
      American early and middle adolescents (N = 420) were assessed over 3 years. Two
      components of ethnic identity were assessed--group-esteem was found to rise for
      both early and middle adolescents; exploration rose for middle adolescents.
      African Americans and Latino Americans were lower in group-esteem but have
      greater increases than European Americans, particularly across a school
      transition. The course of ethnic identity development during early and middle
      adolescence, the role of school context, and the variability in developmental
      trajectories among racial and ethnic groups are discussed.

PMID- 16420115
TI  - Sex differences in math performance: The role of children's approach to
      schoolwork.
AB  - This research examined whether the tendency for girls to outperform boys in the
      classroom is due to differences in how girls and boys approach schoolwork. In 5th
      grade and then again in 7th grade, children (N=518) reported on how they approach
      schoolwork (i.e., achievement goals and classroom behavior), their learning
      strategies, and their self-efficacy in math; math grades and achievement test
      scores were also collected. Girls were more likely than boys to hold mastery over
      performance goals and to refrain from disruptive classroom behavior, which
      predicted girls' greater effortful learning over time. The sex difference in
      learning strategies accounted for girls' edge over boys in terms of grades. Girls
      did not do better on achievement tests, possibly because self-efficacy, for which
      there was also no sex difference, was the central predictor of performance on
      achievement tests.

PMID- 16420116
TI  - Longitudinal prediction of child outcomes from differing measures of parenting in
      a low-income sample.
AB  - This study examined predictions from preschool parenting measures to middle
      childhood cognitive and socioemotional child outcomes to explore whether
      parenting assessment methodologies that require more time, training, and expense
      yield better predictions of child outcomes than less intensive methodologies.
      Mother-child dyads (N = 278) in low-income African American families were
      assessed when the child was in preschool, using maternal report, the Home
      Observation for Measurement of the Environment-Short Form (P. Baker & F. Mott,
      1989; R. Bradley & B. Caldwell, 1984), and structured observational measures of
      parenting. Child outcomes reported by children, mothers, teachers, and direct
      assessment were collected 4 years later. All parenting methodologies showed some
      predictive value; however, observational parenting measures showed the strongest
      and most consistent predictions of child outcomes.

PMID- 16420117
TI  - Infant-mother attachment classification: risk and protection in relation to
      changing maternal caregiving quality.
AB  - The relations between early infant-mother attachment and children's social
      competence and behavior problems during the preschool and early school-age period
      were examined in more than 1,000 children under conditions of decreasing, stable,
      and increasing maternal parenting quality. Infants' Strange Situation attachment
      classifications predicted mothers' reports of children's social competence and
      teachers' reports of externalizing and internalizing behaviors from preschool age
      through 1st grade. These relations appeared to be mediated by parenting quality;
      main effects of attachment classification disappeared when effects of parenting
      quality were controlled. Interactions were also observed. For example, when
      parenting quality improved over time, teachers rated children with insecure
      infant-mother attachments lower on externalizing behaviors; when parenting
      quality decreased, teachers rated insecure children higher on externalizing
      behaviors. In contrast, children classified as securely attached in infancy did
      not appear to be affected by declining or improving parenting quality.

PMID- 16420118
TI  - Preschool children's mathematical knowledge: The effect of teacher "math talk.".
AB  - This study examined the relation between the amount of mathematical input in the
      speech of preschool or day-care teachers and the growth of children's
      conventional mathematical knowledge over the school year. Three main findings
      emerged. First, there were marked individual differences in children's
      conventional mathematical knowledge by 4 years of age that were associated with
      socioeconomic status. Second, there were dramatic differences in the amount of
      math-related talk teachers provided. Third, and most important, the amount of
      teachers' math-related talk was significantly related to the growth of
      preschoolers' conventional mathematical knowledge over the school year but was
      unrelated to their math knowledge at the start of the school year.

PMID- 16420119
TI  - Math and science motivation: A longitudinal examination of the links between
      choices and beliefs.
AB  - This study addresses the longitudinal associations between youths' out-of-school
      activities, expectancies-values, and high school course enrollment in the domains
      of math and science. Data were collected on 227 youth who reported on their
      activity participation in 5th grade, expectancies-values in 6th and 10th grade,
      and courses taken throughout high school. Math and science course grades at 5th
      and 10th grade were gathered through school record data. Results indicated
      youths' math and science activity participation predicted their expectancies and
      values, which, in turn, predicted the number of high school courses above the
      predictive power of grades. Although there were mean-level differences between
      boys and girls on some of these indicators, relations among indicators did not
      significantly differ by gender.

PMID- 16420120
TI  - Emotional self-regulation in preschoolers: The interplay of child approach
      reactivity, parenting, and control capacities.
AB  - This study examined whether child temperamental approach reactivity moderated the
      association between 2 factors, parenting and child control capacities and child
      emotional self-regulation. Participants (N = 113) were 3- and 4-year-olds (M = 48
      months, SD = 5.78) and their mothers. Emotional self-regulation was measured as
      observed persistence and frustration and as maternal report of compliance.
      Parental approach, avoidance, control, and warmth were observed during play and a
      frustrating wait. Child approach reactivity and control capacities (inhibitory
      control and soothability) were assessed via maternal report. Results suggested
      that maternal approach during the wait was associated with persistence and
      frustration, whereas maternal warmth during the play was associated with
      compliance. These effects, and those of child control capacities, depended on the
      level of child approach. The implications of reactivity-control interactions and
      parent-child goodness-of-fit for emotional self-regulation are discussed.

PMID- 16420121
TI  - Picking up speed in understanding: Speech processing efficiency and vocabulary
      growth across the 2nd year.
AB  - To explore how online speech processing efficiency relates to vocabulary growth
      in the 2nd year, the authors longitudinally observed 59 English-learning children
      at 15, 18, 21, and 25 months as they looked at pictures while listening to speech
      naming one of the pictures. The time course of eye movements in response to
      speech revealed significant increases in the efficiency of comprehension over
      this period. Further, speed and accuracy in spoken word recognition at 25 months
      were correlated with measures of lexical and grammatical development from 12 to
      25 months. Analyses of growth curves showed that children who were faster and
      more accurate in online comprehension at 25 months were those who showed faster
      and more accelerated growth in expressive vocabulary across the 2nd year.

PMID- 16420122
TI  - Sociocultural influences on the development of verbal mediation: Private speech
      and phonological recoding in Saudi Arabian and British samples.
AB  - Cross-national stability in private speech (PS) and short-term memory was
      investigated in Saudi Arabian (n = 63) and British (n = 58) 4- to 8-year-olds.
      Assumed differences in child-adult interaction between the 2 nationality groups
      led to predictions of Gender x Nationality interactions in the development of
      verbal mediation. British boys used more self-regulatory PS than British girls,
      whereas there was no such difference for the Saudi group. When age, verbal
      ability, and social speech were controlled, boys used slightly more self
      regulatory PS than girls. Self-regulatory PS was related to children's use of
      phonological recoding of visually presented material in a short-term memory task,
      suggesting that PS and phonological recoding represent different facets of a
      domain-general transition toward verbal mediation in early childhood.

PMID- 16420123
TI  - Contingency, imitation, and affect sharing: Foundations of infants' social
      awareness.
AB  - Predictions about the role of contingency, imitation, and affect sharing in the
      development of social awareness were tested in infants during natural, imitative,
      and yoked conditions with their mothers at 5 and 13 weeks of age. Results showed
      that at both ages, infants of highly attuned mothers gazed, smiled, and vocalized
      positively more during the natural than during the imitative and yoked
      conditions, whereas they increased negative vocalizations during the yoked
      conditions. In contrast, infants of less attuned mothers did not differentiate
      between the conditions, except at 13 weeks when these infants increased their
      gazes during the imitative condition. Whereas contingency and imitation draw
      infant attention to conspecifics, affective communication appears to lay the
      foundation for infants' social awareness.

PMID- 16420124
TI  - Children's use of the temporal dimension of gaze for inferring preference.
AB  - This study examined 4- and 5-year-olds' ability to spontaneously use the relative
      duration and frequency of another's object-directed gaze for inferring that
      person's preference. In Experiment 1, analysis revealed a strong age effect for
      judgment accuracy, which could not be accounted for by cue-monitoring
      proficiency. Reducing the saliency of the objects in Experiment 2 yielded
      significant improvement in the younger children's performance. Thus, at 4 years,
      children already show signs of attending to the temporal dimension of gaze for
      making mentalistic inferences of preferential liking, but their competence may be
      undermined by the object choices themselves. By 5 years, they appear to overcome
      this competition. The obtained developmental difference is discussed in terms of
      concurrent transitions in attention regulation.

PMID- 16420125
TI  - Friend influence on prosocial behavior: The role of motivational factors and
      friendship characteristics.
AB  - This study examined motivation (prosocial goals), individual characteristics
      (sex, ethnicity, and grade), and friendship characteristics (affective quality,
      interaction frequency, and friendship stability) in relation to middle
      adolescents' prosocial behavior over time. Ninth- and 10th-grade students (N =
      208) attending a suburban, mid-Atlantic public high school and having at least 1
      reciprocated friendship were followed for 1 year. Hierarchical regression
      analyses revealed that a friend's behavior is related to an individual's
      prosocial goal pursuit, which in turn, is related to an individual's prosocial
      behavior. Further, the affective quality of a friendship and the frequency with
      which friends interact moderate relations of a friend's prosocial behavior to an
      individual's prosocial goal pursuit.

PMID- 16420126
TI  - Effects of language intervention on syntactic skill levels in preschoolers.
AB  - Questions concerning the role of input in the growth of syntactic skills have
      generated substantial debate within psychology and linguistics. The authors
      address these questions by investigating the effects of experimentally
      manipulated input on children's skill with the passive voice. The study involved
      72 four-year-olds who listened to stories containing either a high proportion of
      passive voice sentences or a high proportion of active voice sentences. Following
      10 story sessions, children's production and comprehension of passives were
      assessed. Intervention type affected performance--children who heard stories with
      passive sentences produced more passive constructions (and with fewer mistakes)
      and showed higher comprehension scores than children who heard stories with
      active sentences. Theoretical implications of these results for the understanding
      of the nature of syntactic skills and practical implications for the development
      of preschool materials are discussed.

PMID- 16420127
TI  - From biological rhythms to social rhythms: Physiological precursors of mother
      infant synchrony.
AB  - Links between neonatal biological rhythms and the emergence of interaction
      rhythms were examined in 3 groups (N = 71): high-risk preterms (HR; birth weight
      <1,000 g), low-risk preterms (LR; birth weight =1,700-1,850 g), and full-term
      (FT) infants. Once a week for premature infants and on the 2nd day for FT
      infants, sleep-wake cyclicity was extracted from 4-hr observations and cardiac
      vagal tone was measured. At term age, infant orientation was tested with the
      Neonatal Behavior Assessment Scale. At 3 months, arousal modulation and emotion
      regulation were assessed, and mother-infant synchrony was computed from
      microanalysis of face-to-face interactions using time-series analysis. Sleep-wake
      amplitudes showed a developmental leap at 31 weeks gestation, followed by a shift
      in vagal tone at 34 weeks gestation. At term, differences among FT, LR, and HR
      infants were observed for biological rhythms in a linear-decline pattern. Sleep
      wake cyclicity, vagal tone, newborn orientation, and arousal modulation were each
      uniquely predictive of mother-infant synchrony. The organization of physiological
      oscillators appears to lay the foundation for the infant's capacity to partake in
      a temporally matched social dialogue.

PMID- 16420128
TI  - Developmental and individual differences in pure numerical estimation.
AB  - The authors examined developmental and individual differences in pure numerical
      estimation, the type of estimation that depends solely on knowledge of numbers.
      Children between kindergarten and 4th grade were asked to solve 4 types of
      numerical estimation problems: computational, numerosity, measurement, and number
      line. In Experiment 1, kindergartners and 1st, 2nd, and 3rd graders were
      presented problems involving the numbers 0-100; in Experiment 2, 2nd and 4th
      graders were presented problems involving the numbers 0-1,000. Parallel
      developmental trends, involving increasing reliance on linear representations of
      numbers and decreasing reliance on logarithmic ones, emerged across different
      types of estimation. Consistent individual differences across tasks were also
      apparent, and all types of estimation skill were positively related to math
      achievement test scores. Implications for understanding of mathematics learning
      in general are discussed.

PMID- 16420131
TI  - Goal-directed memory: the role of cognitive control in older adults' emotional
      memory.
AB  - The present study revealed that older adults recruit cognitive control processes
      to strengthen positive and diminish negative information in memory. In Experiment
      1, older adults engaged in more elaborative processing when retrieving positive
      memories than they did when retrieving negative memories. In Experiment 2, older
      adults who did well on tasks involving cognitive control were more likely than
      those doing poorly to favor positive pictures in memory. In Experiment 3, older
      adults who were distracted during memory encoding no longer favored positive over
      negative pictures in their later recall, revealing that older adults use
      cognitive resources to implement emotional goals during encoding. In contrast,
      younger adults showed no signs of using cognitive control to make their memories
      more positive, indicating that, for them, emotion regulation goals are not
      chronically activated.

PMID- 16420132
TI  - Aging, source memory, and emotion.
AB  - In 2 experiments we assessed younger and older adults' ability to remember
      contextual information about an event. Each experiment examined memory for 3
      different types of contextual information: (a) perceptual information (e.g.,
      location of an item); (b) conceptual, nonemotional information (e.g., quality of
      an item); and (c) conceptual, emotional information (e.g., safety of an item).
      Consistent with a large literature on aging and source memory, younger adults
      outperformed older adults when the contextual information was perceptual in
      nature and when it was conceptual, but not emotional. Age differences in source
      memory were eliminated, however, when participants recalled emotional source
      information. These findings suggest that emotional information differentially
      engages older adults, possibly evoking enhanced elaborations and associations.
      The data are also consistent with a growing literature, suggesting that emotional
      processing remains stable with age (e.g., Carstensen & Turk-Charles, 1994, 1998;
      Isaacowitz, Charles, & Carstensen, 2000).

PMID- 16420133
TI  - No aging bias favoring memory for positive material: evidence from a
      heterogeneity-homogeneity list paradigm using emotionally toned words.
AB  - Some authors argue for a memory advantage of older adults for positively toned
      material. To investigate the contribution of selective processing to a positivity
      effect, the authors investigated young (n = 72, aged 18 to 31) and older (n = 72,
      aged 64 to 75) adults' memory for emotionally toned words using a multitrial
      paradigm that compares performance for heterogeneous (mixed valence) and
      homogeneous (single valence) lists. Regarding the age comparison, there was no
      evidence for an aging bias favoring positive material. Moreover, older adults'
      memory was less affected by emotion-based processing prioritization. Although
      there was no support for age-specific processing biases in memory for emotionally
      toned words, the findings are consistent with proposals that negative information
      receives processing priority in some contexts. Possible limits to the
      generalizability of the present findings (e.g., to nonverbal material) are
      discussed.

PMID- 16420130
TI  - Divergent trajectories in the aging mind: changes in working memory for affective
      versus visual information with age.
AB  - Working memory mediates the short-term maintenance of information. Virtually all
      empirical research on working memory involves investigations of working memory
      for verbal and visual information. Whereas aging is typically associated with a
      deficit in working memory for these types of information, recent findings
      suggestive of relatively well-preserved long-term memory for emotional
      information in older adults raise questions about working memory for emotional
      material. This study examined age differences in working memory for emotional
      versus visual information. Findings demonstrate that, despite an age-related
      deficit for the latter, working memory for emotion was unimpaired. Further, older
      adults exhibited superior performance on positive relative to negative emotion
      trials, whereas their younger counterparts exhibited the opposite pattern.

PMID- 16420134
TI  - The differential effects of mood on age differences in the correspondence bias.
AB  - The present study found that age-related differences in the correspondence bias
      were differentially influenced by induced mood. Young and older adults completed
      an attitude-attribution task after having been induced to experience a positive,
      neutral, or negative mood. Although negative moods intensified age-related
      differences in the correspondence bias, young and older adults were equally
      susceptible to the correspondence bias when in a positive mood. In addition,
      induced mood differentially influenced the attributional confidence of young and
      older adults. Whereas negatively induced young adults were less confident than
      positively induced young adults in their attributions, negatively induced older
      adults were more confident than positively induced older adults in their
      attributions. Findings are discussed in terms of how positive and negative moods
      operate differently in motivating young and older adults' attributional
      judgments.

PMID- 16420136
TI  - The role of visual attention in predicting driving impairment in older adults.
AB  - This study evaluated the role of visual attention (as measured by the DriverScan
      change detection task and the Useful Field of View Test [UFOV]) in the prediction
      of driving impairment in 155 adults between the ages of 63 and 87. In contrast to
      previous research, participants were not oversampled for visual impairment or
      history of automobile accidents. Although a history of automobile accidents
      within the past 3 years could not be predicted using any variable, driving
      performance in a low-fidelity simulator could be significantly predicted by
      performance in the change detection task and by the divided and selection
      attention subtests of the UFOV in structural equation models. The sensitivity and
      specificity of each measure in identifying at-risk drivers were also evaluated
      with receiver operating characteristic curves.

PMID- 16420135
TI  - Treatment of depression in low-income older adults.
AB  - The purpose of this study was to compare cognitive-behavioral group therapy
      (CBGT), clinical case management (CCM), and their combination (CBGT + CCM) to
      treat depression in low-income older adults (60+). Sixty-seven participants with
      major depressive disorder or dysthymia were randomly assigned and entered into 1
      of the 3 treatment conditions for 6 months. They were followed for 18 months
      after treatment initiation on depression and functional outcomes. CCM and CBGT +
      CCM led to greater improvements in depressive symptoms than CBGT, but CBGT led to
      greater improvements in physical functioning. All 3 conditions resulted in
      similar reduction of needs. Findings suggest that disadvantaged older adults with
      depression benefit from increased access to social services either alone or
      combined with psychotherapy.

PMID- 16420137
TI  - Cognitive performance inconsistency: intraindividual change and variability.
AB  - Although many studies have examined inconsistency of cognitive performance, few
      have examined how inconsistency changes over time. 91 older adults (age 52 to 79)
      were tested weekly for 36 consecutive weeks on a series of multitrial memory
      speed (i.e., letter recognition) tasks. A number of multivariate techniques were
      used to examine how individuals' level of inconsistency changed across weeks and
      how this change was related to interindividual differences in age and
      intelligence. Results indicated that (a) inconsistency of performance is a
      construct separate from the underlying performance ability (i.e., memory speed);
      (b) inconsistency reduces exponentially with practice; (c) individuals with
      higher scores on tests of fluid general intelligence (G-sub(f)) reached lower
      asymptotic levels of inconsistency compared to lower scorers; and (d) after
      controlling for the systematic effects of practice, variability in inconsistency
      from week-to-week was more pronounced for individuals with lower G-sub(f) scores
      compared to individuals with higher scores.

PMID- 16420138
TI  - Changes in social support as mediators of the impact of a psychosocial
      intervention for spouse caregivers of persons with Alzheimer's disease.
AB  - The spouse caregivers of 406 patients with Alzheimer's disease were randomly
      assigned to an enhanced counseling and support intervention or to a usual care
      control condition. Structured interviews were conducted to assess changes in
      social support and psychosocial outcomes for the 312 caregivers who provided care
      in the home for at least 1 year. The number of support persons, satisfaction with
      the support network, and support persons' assistance with caregiving all
      increased significantly as a function of the intervention. Structural equation
      models indicated increased satisfaction with the social support network mediated
      a significant proportion of the intervention's impact on caregiver depression. A
      portion of this mediated effect was further mediated by changes in caregiver
      stress appraisals. Implications for strengthening intervention programs for
      spouse caregivers of individuals with Alzheimer's disease are discussed.

PMID- 16420139
TI  - Explaining age differences in temporal working memory.
AB  - To determine the cognitive mechanisms underlying age differences in temporal
      working memory (WM), the authors examined the contributions of item memory,
      associative memory, simple order memory, and multiple item memory, using parallel
      versions of the delayed-matching-to-sample task. Older adults performed more
      poorly than younger adults on tests of temporal memory, but there were no age
      differences in nonassociative item memory, regardless of the amount of
      information to be learned. In contrast, a combination of associative and simple
      order memory, both of which were reduced in older adults, completely accounted
      for age-related declines in temporal memory. The authors conclude that 2
      mechanisms may underlie age differences in temporal WM, namely, a generalized
      decline in associative ability and a specific difficulty with order information.

PMID- 16420140
TI  - Regret and quality of life across the adult life span: the influence of
      disengagement and available future goals.
AB  - Two studies examined the associations between life regrets and indicators of
      quality of life across the adult life span. Given that opportunities to undo
      regrets decline with age, regret intensity was expected to be inversely
      associated with subjective well-being and health among older adults. In addition,
      the research explored protective factors that have the potential to reduce older
      adults' regret intensity. It was suggested that being disengaged from undoing the
      consequences of regrets and having many future goals available may reduce older
      adults' intensity of regret and thereby contribute to a better quality of life.
      Across both studies, the findings demonstrate that older adults perceived reduced
      opportunities to undo the consequences of their regrets and that regret intensity
      predicted a reduced quality of life only among older adults. Furthermore, the
      findings support the adaptive value of disengagement and available future goals
      for managing life regrets in older adults.

PMID- 16420141
TI  - A dynamic investigation of cognitive dedifferentiation with control for retest:
      evidence from the Swiss Interdisciplinary Longitudinal Study on the Oldest Old.
AB  - Empirical examinations of the hypothesis of dedifferentiation of cognitive
      abilities in old and very old age (a) do not account for possible retest effects,
      which consequently may yield biased estimates of age effects, and (b) focus on
      time-independent relations (e.g., number of latent constructs, correlations
      between latent or measured variables). The authors applied a structural equation
      model with statistical control for retest effects to investigate the dynamic
      relations between a marker of perceptual speed (cross out) and a marker of verbal
      fluency (category-fruits). Longitudinal data are from 5 waves of the Swiss
      Interdisciplinary Longitudinal Study on the Oldest Old (N = 377, baseline age
      range = 79.5- 84.5 years). The authors found that, independently of retest
      effects, performance on the cross-out task affected changes in performance on the
      category task while the opposite did not hold true. This analytical technique
      could be applied to various markers of broad fluid-mechanic and broad
      crystallized-pragmatic components of cognition.

PMID- 16420142
TI  - Environmental topography and postural control demands shape aging-associated
      decrements in spatial navigation performance.
AB  - This study tests the hypothesis that aging-induced cognitive permeation of
      sensorimotor functions contributes to adult age differences in spatial navigation
      performance. Virtual maze-like museums were projected in front of a treadmill.
      Sixteen 20-30-year-old men and sixteen 60-70-year-old men performed a way-finding
      task in city-block or variable topographies while walking with or without
      support. Walking support attenuated age-related decrements in navigational
      learning. Navigation load increased trunk-angle variability for older adults
      only. Age differences in spatial knowledge persisted despite perfect place
      finding performance. City-block topography was easier than variable topography
      for younger adults only, indicating age-related differences in reliance on
      spatial relational learning. Attempts at supporting older adults' navigation
      performance should consider sensorimotor/cognitive interactions and qualitative
      differences in navigational activity.

PMID- 16420143
TI  - Training effects on dual-task performance: are there age-related differences in
      plasticity of attentional control?
AB  - A number of studies have suggested that attentional control skills required to
      perform 2 tasks concurrently become impaired with age (A. A. Hartley, 1992; J. M.
      McDowd & R. J. Shaw, 2000). A. A. Hartley (2001) recently observed that the age
      related differences in dual-task performance were larger when the 2 tasks
      required similar motor responses. The present study examined the extent to which
      age-related deficits in dual-task performance or time sharing--in particular,
      dual-task performance of 2 discrimination tasks with similar motor requirements-
      can be moderated by training. The results indicate that, even when the 2 tasks
      required similar motor responses, both older and younger adults could learn to
      perform the tasks faster and more accurately. Moreover, the improvement in
      performance generalized to new task combinations involving new stimuli.
      Therefore, it appears that training can substantially improve dual-task
      processing skills in older adults.

PMID- 16420144
TI  - Aging holocaust survivors' well-being and adjustment: associations with
      ambivalence over emotional expression.
AB  - A sample of 90 older respondents (age range: 78-83 years) composed of 2 Holocaust
      groups (camp inmates and other survivors) and a comparison group completed
      questionnaires measuring ambivalence over emotional expression, positive and
      negative affect, and psychosocial adjustment. The Holocaust groups rated higher
      than the comparison group on negative affect and ambivalence over emotional
      expression and lower on psychosocial adjustment. Ambivalence over emotional
      expression mediated the effects of the Holocaust on negative affect. These data
      suggest that the effects of the Holocaust are evident 60 years later,
      highlighting the role of ambivalence over emotional expression in the well-being
      of Holocaust survivors.

PMID- 16420145
TI  - Exploring age differences in the stress-buffering function of social support.
AB  - The purpose of this study is to see if there are age differences in the
      relationship between chronic financial strain, emotional support, and life
      satisfaction among people aged 65 and older. Data from a nationwide survey of
      older people (N = 1,518) indicate that emotional support tends to reduce the
      noxious effects of economic problems on life satisfaction for the sample as a
      whole. However, the findings further reveal that the potential benefits of
      emotional support arise primarily among the oldest-old. In contrast, emotional
      support does not offset the negative effects of financial strain on life
      satisfaction among the young-old.

PMID- 16420146
TI  - Memory for grocery prices in younger and older adults: the role of schematic
      support.
AB  - The present study examined how younger and older adults remember price
      information. Participants studied grocery items that were priced at market value
      or were well above or below market value. Although younger adults displayed
      better recall performance for unrealistic prices than older adults, there was no
      age difference for realistic prices, and both groups were equally accurate at
      remembering the general price range of the items. The results suggest that when
      older adults can rely on prior knowledge and schematic support, and tasks involve
      naturalistic materials, memory for associative information can be as good as that
      of younger adults.

PMID- 16420147
TI  - Androgen deprivation impairs memory in older men.
AB  - Androgen deprivation leads to a profound loss of synaptic density in the
      hippocampus and changes in learning and memory in animal models. The authors
      examined group differences in verbal memory between men on androgen deprivation
      therapy (ADT), a commonly used treatment for prostate cancer, and healthy men.
      The authors found that men on ADT have a specific impairment of retention but
      normal encoding and retrieval processes on a word list-learning task. Speed and
      accuracy for both perceptual and semantic encoding, as well as retrieval at a
      very short retention interval, were not affected; however, recognition fell to
      chance after a 2-min retention interval in men on ADT. Healthy men showed only
      moderate forgetting, and performance was still above chance at 12 min. This
      pattern of preserved encoding and retrieval but impaired retention suggests that
      androgens play a role in hippocampally mediated memory processes, possibly having
      a specific affect on consolidation.

PMID- 16420148
TI  - Cortico-striatal contributions to category learning: dissociating the verbal and
      implicit systems.
AB  - To better characterize the neuropsychological mechanisms of implicit and
      verbalizable category learning, the author studied weather prediction task (WPT)
      and information integration task (IIT) performance in patients with Parkinson's
      disease (PD) and healthy older and younger adults. Both older adults and patients
      with PD were impaired on the WPT, but only patients were impaired on the IIT,
      suggesting the 2 tasks rely on dissociable systems. Whereas the IIT appeared to
      rely on implicit processes, results suggest WPT classification depends on
      explicit processes. Awareness of underlying structure, hypothesis testing
      ability, and working memory capacity were all related to accuracy on the WPT but
      not the IIT. The variability commonly noted in WPT performance may reflect
      individual differences in hypothesis testing ability.

PMID- 16420149
TI  - Corticotropin-releasing factor-1 receptors in the basolateral amygdala mediate
      stress-induced anorexia.
AB  - Corticotropin-releasing factor (CRF) receptor activation within the basolateral
      amygdala (BLA) has been relatively unexplored compared with the central nucleus
      of the amygdala (CeA), despite the fact that CRF receptors are more densely
      distributed in BLA than in CeA. The authors show that infusion of CRF into BLA,
      but not CeA, decreases feeding and increases grooming. These effects are mediated
      by CRF-sub-1 receptors, because they are blocked by intra-BLA treatment with
      NBI27914 (NBI), a CRF-sub-1 antagonist, but not Astressin 2B, a CRF-sub-2
      antagonist. Exposure to a stressor results in behaviors identical to those seen
      after intra-BLA CRF infusion. These stress-induced changes are prevented by pre
      stress treatment with NBI but not Astressin 2B. These data demonstrate that
      stimulation of intra-BLA CRF-sub-1 receptors is both necessary and sufficient for
      eliciting stress-induced anorexia and grooming.

PMID- 16420151
TI  - Behavioral expression of learned fear: updating of early memories.
AB  - The expression of learned fear emerges in a response-specific sequence where
      freezing occurs before fear potentiated startle (FPS) to an odor conditioned
      stimulus (CS; Postnatal Day [PN] 16 vs. PN 23; e.g., Hunt, 1997; Richardson,
      Paxinos, & Lee, 2000). Studies have shown that learned fear is expressed in a
      manner appropriate to the animal's age at training and not its age at test
      (Richardson & Fan, 2002; Richardson et al., 2000). Specifically, animals trained
      with an odor CS at PN 16 exhibit avoidance but not FPS when tested at PN 23. The
      present study shows that subsequent training with a different CS can "update" an
      early memory, allowing it to be expressed in a manner appropriate to the animal's
      age at test. This updating effect appears to be modality specific, whereby the
      subsequent training must involve a CS of the same sensory modality as the
      original training.

PMID- 16420152
TI  - Comparison of anxiety-like behavior in adolescent and adult Sprague-Dawley rats.
AB  - The conditions under which age differences in anxiety are observed in rodents are
      unclear. These studies explored the influence of test condition on anxiety-like
      behavior in adolescent and adult rats using the light-dark box. Behavior was
      assessed under different illumination levels (30 or 60 lux) and after brief
      stress (restraint or bright light). Anxiety-like behavior did not differ in the
      30-lux test but was increased in adolescents in the 60-lux test. Restraint
      increased anxiety-like behavior in adolescents, resulting in elevated anxiety
      like behavior relative to adults. Bright light decreased anxiety-like behavior,
      possibly because of negative contrast or novelty-induced anxiolysis. These
      studies demonstrate that adolescents display increased anxiety-like behavior when
      test conditions are more aversive and following exposure to stress.

PMID- 16420153
TI  - Conditioning-specific reflex modification of rabbit (Oryctolagus cuniculus) heart
      rate.
AB  - Conditioning-specific reflex modification (CRM) describes changes in rabbit
      (Oryctolagus cuniculus) nictitating membrane responses (NMR) to an unconditioned
      stimulus (US) when the US is tested by itself after pairings of tone and
      electrodermal stimulation. Although CRM has been replicated, it is unclear
      whether it occurs in response systems other than that of the NMR. The authors
      report that CRM of rabbit heart rate (HR) can occur following HR conditioning. A
      US that elicits HR acceleration before conditioning can elicit HR deceleration
      after conditioning. The rabbits' electrocardiograms showed both HR conditioning
      and HR CRM were correlated with an increased PQ interval--an index of
      parasympathetic function mediated by the vagus. The data suggest conditioned HR
      deceleration can generalize from conditioned stimulus to US as a function of
      conditioning.

PMID- 16420150
TI  - The bed nucleus of the stria terminalis is critically involved in enhancing
      associative learning after stressful experience.
AB  - Exposure to an acute stressful event enhances trace eyeblink conditioning in male
      rats, even when rats begin training days after the stressor (Shors, 2001). The
      authors examined whether the bed nucleus of the stria terminalis (BNST), an area
      involved in stress and anxiety, is critically involved in this effect and, if so,
      when. The authors found that excitotoxic lesions to the BNST prevented the
      enhanced conditioning after stressor exposure. In addition, temporary
      inactivation of the BNST during the stressor did not alter enhanced responding,
      whereas inactivation during training prevented the enhancement. These data
      indicate that stressful experience induces persistent changes in the BNST that
      are necessary for enhancing learning well after the stressful event has ceased.

PMID- 16420154
TI  - Single neurons in the medial prefrontal cortex of the rat exhibit tonic and
      phasic coding during trace fear conditioning.
AB  - Trace fear conditioning is a learning task that requires the association of an
      auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that
      are separated by a 20-s trace interval. Single neuron activity was recorded from
      the prelimbic and infralimbic areas of the medial prefrontal cortex in rats
      during trace fear conditioning or nonassociative unpaired training. Prelimbic
      neurons showed learning-related increases in activity to the CS and US, whereas
      infralimbic neurons showed learning-related decreases in activity to these
      stimuli. A subset of prelimbic neurons exhibited sustained increases in activity
      during the trace interval. These sustained prelimbic responses may provide a
      bridging code that allows for overlapping representations of CS and US
      information within the trace fear conditioning circuit.

PMID- 16420155
TI  - The formation of cognitive maps of adjacent environments: evidence from the head
      direction cell system.
AB  - In 2 experiments the authors tested whether the head direction (HD) cell system
      underlies a sense of direction maintained across environments. In Experiment 1,
      HD neurons failed to maintain their firing directions across T mazes in adjacent
      environments but rather reoriented to the T maze within each environment. Such
      reorientation suggests that familiar landmarks override an internal directional
      sense, so in Experiment 2 the authors recorded HD neurons as rats walked between
      novel and familiar "rooms" of a 4-chamber apparatus. In novel rooms, HD neurons
      maintained the firing direction of the preceding environment. However, in
      familiar rooms, HD neuron firing directions shifted to agree with the landmarks
      therein. With repeated experience, a homogeneous representation of all rooms
      developed in a subset of the rats.

PMID- 16420156
TI  - Cingulate cortical coding of context-dependent latent inhibition.
AB  - Neuronal activity of the auditory thalamus, amygdala, cingulate cortex, and
      substantia nigra was recorded during the administration of a behavioral test for
      latent inhibition (LI) or the retardation of behavioral conditioning because of
      preexposure of the conditional stimulus (CS). Following CS preexposure, both the
      preexposed CS and a control CS predicted avoidable footshock. LI occurred as
      significantly fewer avoidance conditioned avoidance responses after the
      preexposed CS than after the control CS. Attenuation of neuronal responses to the
      preexposed CS, or neural LI, occurred in all monitored areas. One group of
      subjects (Oryctolagus cuniculus) then received context extinction, and additional
      groups experienced novel context exposure or handling. Context extinction
      enhanced behavioral responding to the preexposed CS, eliminating LI. Context
      extinction also eliminated cingulate cortical neural LI by enhancing posterior
      cingulate cortical responses to the preexposed CS and attenuating anterior
      cingulate cortical responses to the control CS. Present and past results are
      interpreted to indicate that LI is (a) a failure of response retrieval and/or
      expression mediated by interfering CS-context associations and (b) a product of
      interactions of the posterior cingulate cortex and the hippocampus.

PMID- 16420157
TI  - The dynamic nature of spatial encoding in the hippocampus.
AB  - Many hippocampal neurons (place cells) appear to represent a particular location
      within an environment (their place field). This property would appear to be
      central to hippocampal involvement in navigation based on spatial memory.
      Although a navigationally useful representation might also include information
      about distal goals, having a place field and being able to represent a distal
      goal would appear to be mutually exclusive place cell properties. Our simulations
      demonstrate, however, that information about goal direction can be simply derived
      from the changes in place field density that occur when place fields shift
      location in a goal-directed manner. Previous reports that place fields respond
      dynamically to shifts in goal location may, therefore, represent the operation of
      such a system.

PMID- 16420158
TI  - Neural network model of prepulse inhibition.
AB  - The authors introduce a real-time model of acoustic prepulse inhibition (PPI) and
      facilitation (PPF) in animals and humans. The model incorporates excitatory and
      facilitatory pathways activated by the positive value of changes in noise level
      in the environment and an inhibitory pathway activated by the absolute value of
      changes in noise level. Whereas excitation and facilitation are exponential
      functions, inhibition is a linear function of the input noise expressed in
      decibels. The model describes many properties of PPI and PPF that include, among
      others, their dependency on prepulse intensity and duration, duration of the lead
      interval, and changes in background noise. The model also describes how specific
      brain lesions enhance the strength of the startle response and impair PPI.
      Finally, the model correctly predicts how PPI depends on pulse intensity.

PMID- 16420159
TI  - Impairment in long-term retention but not short-term performance on a water maze
      reversal task following hippocampal or mediodorsal striatal N-methyl-D-aspartate
      receptor blockade.
AB  - Male Long-Evans rats were injected with 32 ng/mul of the N-methyl-D-aspartate
      (NMDA) receptor antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid
      (CPP) or vehicle and trained to locate a hidden platform in a different location
      (reversal training) than used on the initial 4 days of training. Rats treated
      with vehicle or CPP into the dorsal hippocampus, basolateral amygdala, or
      mediodorsal striatum had similar latencies to locate the platform on the reversal
      day. Rats infused with CPP into the dorsal hippocampus or mediodorsal striatum
      failed to search preferentially in the novel location during a 24-hr, drug-free
      retention test, whereas all other groups searched preferentially in this
      location. Therefore, blocking dorsal hippocampal or mediodorsal striatal NMDA
      receptors selectively blocked long-term spatial retention without producing short
      term performance deficits.

PMID- 16420160
TI  - Conditioned effects of kindling three different sites in the hippocampal complex
      of the rat.
AB  - Rats received kindling stimulations to the perirhinal cortex (PRh), ventral
      hippocampus (VH), or dorsal hippocampus (DH) in 1 environment and an equivalent
      number of sham stimulations in a 2nd environment. The PRh-kindled rats displayed
      rapid kindling and a swift emergence of conditioned interictal defensiveness. In
      contrast, the VH- and DH-kindled rats displayed much slower kindling and slow or
      no conditioning, respectively. No effects of conditioning on the convulsions,
      comparable with those associated with amygdala kindling, were observed. These
      results establish the generality of some of the previously reported kindling
      related conditioned effects, confirm the site specificity of some of these
      effects, and suggest that the convulsions, rather than the stimulations, function
      as the unconditioned stimuli for the conditioning of interictal behavior.

PMID- 16420161
TI  - Specific changes in conditioned responding following neurotoxic damage to the
      posterior parietal cortex.
AB  - The central nucleus (CN) of the amygdala and basal forebrain cholinergic
      projections to the posterior parietal cortex (PPC) are involved in regulating
      changes in attentional processing of conditioned stimuli. In a previous study,
      lesions of the CN produced a deficit in conditioned orienting behavior (rearing
      on the hind legs) when a visual stimulus was paired with food. Unconditioned
      orienting (rearing to nonreinforced presentations of the stimulus) and
      conditioned food cup behavior were unaffected. The present study examined the
      contribution of the PPC to attentional orienting behavior. Damage to the PPC did
      not affect orienting behavior but produced deficits in food cup behavior. These
      findings help define the specific contributions of the PPC to attentional
      processing and associative learning.

PMID- 16420162
TI  - The effects of D1 or D2 dopamine receptor antagonism in the medial preoptic area,
      ventral pallidum, or nucleus accumbens on the maternal retrieval response and
      other aspects of maternal behavior in rats.
AB  - The medial preoptic area (MPOA), ventral pallidum (VP), and nucleus accumbens
      (NA) receive dopaminergic afferents and are involved in maternal behavior.
      Experiments investigated whether dopamine (DA) receptor antagonism in NA disrupts
      maternal behavior, determined the type of DA receptor involved, and investigated
      the involvement of drug spread to VP or MPOA. Injection of SCH 23390 (D1 DA
      receptor antagonist) into NA of postpartum rats disrupted retrieving at dosage
      levels that were ineffective when injected into MPOA or VP. Motor impairment was
      not the cause of the deficit. Injection of eticlopride (D2 DA receptor
      antagonist) into NA or VP was without effect. Results emphasize the importance of
      DA action on D1 receptors in NA for retrieval behavior.

PMID- 16420164
TI  - Cocaine craving, euphoria, and self-administration: a preliminary study of the
      effect of catecholamine precursor depletion.
AB  - The authors used the acute phenylalanine-tyrosine depletion (APTD) method to test
      the effect of transient catecholamine precursor depletion on cocaine craving,
      euphoria, and self-administration. Eight nondependent, nontreatment-seeking
      cocaine users self-administered 3 doses of cocaine (0.6, 1.5, 3.0 mg/kg, taken
      intranasally) following ingestion of (a) a nutritionally balanced amino acid
      mixture, (b) APTD, and (c) APTD followed by L-dopa/carbidopa (2x100 mg/25 mg).
      APTD decreased both cue and cocaine-induced drug craving but not euphoria or self
      administration. APTD+L-dopa also decreased drug craving, possibly reflecting the
      ability of L-dopa to transiently decrease dopamine cell firing. Together, these
      preliminary results suggest that the craving elicited by cocaine and cocaine cues
      is related to changes in catecholamine neurotransmission. Euphoria and the self
      administration of freely available drugs by regular users, in comparison, might
      be better accounted for by other mechanisms.

PMID- 16420163
TI  - Cocaine treatment and prenatal environment interact to disrupt intergenerational
      maternal behavior in rats.
AB  - The link between impaired maternal behavior (MB) and cocaine treatment could
      result from drug-induced decreases in maternal reactivity to offspring, prenatal
      drug exposure (PDE) in offspring that could alter their ability to elicit MB, or
      the interaction of both, which could subsequently impair MB of the 1st-generation
      dams. Following chronic or intermittent cocaine or saline treatment during
      gestation, rat dams rearing natural or cross-fostered litters were compared along
      with untreated dams for MB. Untreated 1st-generation females with differentially
      treated rearing dams and PDE were tested for MB with their natural litters. The
      authors report disruptions in MB in dams and their 1st-generation offspring,
      attributable to main and interaction effects of maternal treatment, litter PDE,
      and rearing experience.

PMID- 16420165
TI  - Social and sexual motivation in the mouse.
AB  - Does a sexual encounter have reward value for a learned operant response?
      Ovariectomized female mice with or without estradiol replacement were trained to
      perform a bar-contact operant response for either male or female targets.
      Response rates of females with estradiol replacement did not differ from those of
      females without estradiol replacement or females responding for access to
      females. Reflexive receptive sexual behavior remained responsive to estradiol
      replacement. Experiment 2 demonstrated that socially isolated females would
      respond faster for access to a female target than when group housed. Finally, the
      oxytocin blocker, atosiban, reduced both operant and reflexive social behavior.
      These results converge on the conclusion that the operant reward value of social
      and sexual contact is primarily social.

PMID- 16420167
TI  - Visual acuity, environmental complexity, and social organization in African
      cichlid fishes.
AB  - The authors studied the effects of habitat complexity and social organization on
      visual acuity in closely related cichlid fishes (the Ectodini clade). The authors
      quantified habitat complexity among sand, intermediate, and rock habitats using
      chromatic difference measures (intensity analysis). Visual acuity was measured
      behaviorally, using optomotor/optokinetic responses to rotating square-wave
      stimuli. The rock-dwelling Asprotilapia leptura exhibited the best visual
      ability, compared with the intermediate and sand-dwelling species, Xenotilapia
      spilotera and Xenotilapia flavipinnis. The authors then compared effects of
      social organization. The lek-forming, polygamous Enantiopus melanogenys showed
      better visual acuity than that of the pair-bonding, monogamous X. flavipinnis.
      The authors' results are the first to demonstrate that species-specific
      differences in visual acuity are associated with differences in both the physical
      and social environment.

PMID- 16420166
TI  - Polycose taste pre-exposure fails to influence behavioral and neural indices of
      taste novelty.
AB  - Taste novelty can strongly modulate the speed and efficacy of taste aversion
      learning. Novel sweet tastes enhance c-Fos-like immunoreactivity (FLI) in the
      central amygdala and insular cortex. The present studies examined whether this
      neural correlate of novelty extends to different taste types by measuring FLI
      signals after exposure to novel and familiar polysaccharide (Polycose) and salt
      (NaCl) tastes. Novel Polycose not only failed to elevate FLI expression in
      central amygdala and insular cortex, but also failed to induce stronger taste
      aversion learning than familiar Polycose. Novel NaCl, on the other hand, showed
      patterns of FLI activation and aversion learning similar to that of novel sweet
      tastes. Possible reasons for the resistance of Polycose to typical pre-exposure
      effects are discussed.

PMID- 16420168
TI  - Effects of blocking nitric oxide on learning in turtles (Chrysemys picta).
AB  - Turtles (Chrysemys picta) were given the nitric oxide synthase inhibitor NW-nitro
      L-arginine methyl ester (L-NAME) or its inactive isomer NW-nitro-D-arginine
      methyl ester (D-NAME) and were trained on a negative patterning task or a simple
      go/no-go discrimination task. L-NAME impaired the learning of negative patterning
      but did not affect retention of the task if it had already been learned. D-NAME
      had no effect. Go/no-go discrimination learning was not affected by L-NAME. These
      findings support the notion that nitric oxide plays a role in complex configural
      learning in a reptile closely related to the ancestors of mammals.

PMID- 16420169
TI  - Reinstatement of extinguished fear by beta-adrenergic arousal elicited by a
      conditioned context.
AB  - Five experiments examined the reinstatement of fear (freezing) produced by recent
      reexposure to a dangerous context. Rats were trained to fear a conditioned
      stimulus (CS) and a distinctive context with shock. The CS was then extinguished.
      A 2-min interval between reexposure to the dangerous context and presentation of
      the extinguished CS in a different context reinstated freezing when the CS was
      tested the next day. Propranolol (a beta-adrenergic antagonist) blocked
      reinstatement of extinguished fear without decreasing freezing to a
      nonextinguished CS. Administration of epinephrine (an adrenergic agonist)
      reinstated extinguished fear without reexposure to the dangerous context. The
      results suggest a role for beta-adrenergic activity elicited by exposure to a
      conditioned context in the reinstatement of extinguished fear.

PMID- 16420170
TI  - Facilitation of fear extinction by midbrain periaqueductal gray infusions of
      RB101(S), an inhibitor of enkephalin-degrading enzymes.
AB  - Mu-opioid receptors in the ventrolateral quadrant midbrain periaqueductal gray
      (vIPAG) contribute to extinction of conditioned fear. The present experiment
      studied whether fear extinction could be facilitated by infusions of a peptidase
      inhibitor that reduces catabolism of vIPAG enkephalins. Rats were trained to fear
      an auditory conditioned stimulus. Fear was then extinguished. Extinction training
      was preceded by infusions of vehicle or RB101(S), an inhibitor of enkephalin
      catabolising enzymes. RB101(S) dose dependently facilitated extinction as indexed
      by performance during extinction and on a drug-free test. This facilitation was
      not observed when RB101(S) was infused outside the vIPAG. These results confirm
      that vIPAG endogenous opioids contribute to fear extinction and show that
      extinction can be facilitated by manipulations that increase vIPAG opioid
      neuromodulation.

PMID- 16420171
TI  - A role for affect in context-dependent sensitization to amphetamine.
AB  - Repeated exposure to stimulant drugs, such as amphetamine, induces sensitization
      to their behavioral activating effects. It is commonly assumed that behavioral
      sensitization is expressed in the environment explicitly paired with the drug but
      not in a different environment explicitly unpaired with the drug. The experiments
      reported here show that this assumption is incorrect. It was found that
      sensitization was expressed in an environment explicitly unpaired with
      amphetamine, but imbued with positive affective valence by its association with a
      natural reward, oral sucrose. These results suggest that the affective valence of
      the environment in which the drug is administered plays a decisive role in the
      expression of drug effects, regardless of any previous association of that
      environment with the drug.

PMID- 16420172
TI  - Selective dysgranular retrosplenial cortex lesions in rats disrupt allocentric
      performance of the radial-arm maze task.
AB  - The present study provides the 1st report on the effects of selective lesions of
      the dysgranular portion of the retrosplenial cortex in rats. Excitotoxic lesions
      of the dysgranular area were sufficient to impair behavior in the radial-arm maze
      by biasing the strategy used to solve the task. In particular, rats with
      dysgranular retrosplenial lesions were less reliant on distal visual cues to
      control performance of a working memory task in the radial-arm maze. Instead,
      they were more reliant on using a motor turning strategy to solve the task. This
      change in strategy is consistent with anatomical data showing that the
      dysgranular region is the primary recipient of visual inputs to the rat
      retrosplenial cortex.

PMID- 16420173
TI  - Involvement of catecholamine neurotransmission in the rat anterior cingulate in
      effort-related decision making.
AB  - This study examined whether catecholamine-mediated signals in the anterior
      cingulate cortex (ACC) contribute to effort-based decision making. Rats were
      tested after 6-hydroxydopamine or vehicle infusions into the ACC in a T maze cost
      benefit task in which the rats could choose either to climb a barrier to obtain a
      high reward in one arm or run into the other arm without a barrier to obtain a
      low reward. Results demonstrate that infusions of 6-hydroxydopamine induced a
      near total loss of tyrosine hydroxylase-positive fibers in the ACC. Unlike sham
      lesioned rats, 6-hydroxydopamine-lesioned rats exhibited a reduced preference for
      the high-cost-high-reward response option when given the choice of obtaining a
      low reward with little effort. Thus, catecholamine-mediated signals in the ACC
      could play a role in effort-based decision making.

PMID- 16420174
TI  - Taste and olfactory intensity perception changes following left insular stroke.
AB  - The authors tested suprathreshold intensity perception of gustatory and olfactory
      stimuli in a 70-year-old right-handed man following a left posterior insular
      stroke and compared his results with those of age-matched controls. Both
      modalities revealed significant differences between left (ipsilateral to lesion)
      and right (contralateral) ratings of intensity. In both gustation and olfaction,
      these differences were driven primarily by trends toward increased contralateral
      sensitivity relative to controls. Intensity changes were most pronounced for
      unpleasant odors and for tastes perceived strongly as either pleasant (sweet) or
      unpleasant (salty, bitter). These results show that a left posterior insula
      lesion may affect taste and olfactory perception similarly by increasing
      sensitivity contralateral to the lesion. One possible mechanism is release from
      inhibition at the cortical level.

PMID- 16420175
TI  - Primary motor cortex asymmetry is correlated with handedness in capuchin monkeys
      (Cebus apella).
AB  - Humans exhibit a population-wide tendency toward right-handedness, and structural
      asymmetries of the primary motor cortex are associated with hand preference.
      Reported are similar asymmetries correlated with hand preference in a New World
      monkey (Cebus apella) that does not display population-level handedness.
      Asymmetry of central sulcus depth is significantly different between left-handed
      and right-handed individuals as determined by a coordinated bimanual task. Left
      handed individuals have a deeper central sulcus in the contralateral hemisphere;
      right-handed individuals have a more symmetrical central sulcus depth. Cerebral
      hemispheric specialization for hand preference is not uniquely human and may be
      more common among primates in general.

PMID- 16420176
TI  - Temporal processing of information: the role of the medial prefrontal cortex and
      hippocampus: theoretical comment on Gilmartin and McEchron (2005).
AB  - M. R. Gilmartin and M. D. McEchron (2005) reported that single cells recorded in
      the prelimbic cortex of rats during the acquisition of trace fear conditioning
      display multiple patterns of neuronal firing during the trace. These finding are
      discussed in the context of the role of the prelimbic cortex in processing
      temporal information during trace conditioning and delayed matching- or
      nonmatching-to-sample paradigms based on both electrophysiology and lesion
      evidence. In addition, evidence is provided for a role of the hippocampus in
      supporting temporal processing of information and its potential interaction with
      the prelimbic cortex.

PMID- 16420177
TI  - Management guidelines for patients with thyroid nodules and differentiated
      thyroid cancer.

PMID- 16420188
TI  - Immobilization of Pycnoporus sanguineus laccase on copper tetra
      aminophthalocyanine-Fe(3)O(4) nanoparticle composite.
AB  - A magnetic nanoparticle composite of CuTAPc (copper tetra-aminophthalocyanine)
      Fe(3)O(4) was prepared by in situ complexation and was characterized by FTIR
      (Fourier-transform IR) spectroscopy, X-ray diffraction, X-ray photoelectron
      spectroscopy, FESEM (field emission scanning electron microscopy) micrograph and
      hysteresis loop. The results showed that CuTAPc formed the covering layer on the
      surface of the composite. Using glutaraldehyde, laccase was covalently attached
      to the surface of the composite. When white-rot-fungus (Pycnoporus sanguineus)
      laccase was immobilized on the CuTAPc-Fe(3)O(4) nanoparticle composite in PBS,
      the optimal reaction pH was 5.0 and the optimal temperature was 0 degrees C. When
      2.0 mg/ml laccase solution was used, the immobilization yield was 20%. The
      activity, K(m), k(cat)/K(m) and V(max) values of the immobilized laccase were
      1.43 units/mg, 2.38 x 10(-5) mol/l, 2.1 x 10(3) mol(-1) x s(-1) x l and 1.19 x
      10(-6) mol x l(-1) /x min(-1) respectively. The system exhibited maximum enzyme
      activity at pH 3.0 and at 45 degrees C. After storage at 4 degrees C for 1 month,
      the residual activity of the immobilized laccase was 85% of its initial activity,
      while that of free laccase was only 30%. During 240 min incubation at 55 degrees
      C, the activity of immobilized laccase quickly increased to a maximum after 150
      min and then decreased to 95% in the next 90 min, while the activity of the free
      enzyme decreased monotonically to 28%. After five consecutive operations, the
      immobilized laccase still retained 80% of its initial activity.

PMID- 16420189
TI  - Synthesis of a precursor dipeptide of RGDS (Arg-Gly-Asp-Ser) catalysed by the
      industrial protease alcalase.
AB  - Synthesis of Bz-Arg-Gly-NH(2) (N-benzoylargininylglycinamide) [a precursor
      dipeptide of RGDS (Arg-Gly-Asp-Ser)] catalysed by protease in water/organic co
      solvent systems was studied. Starting substrates were N-benzoyl-L-arginine ethyl
      ester hydrochloride (acyl donor) and glycinamide (nucleophile). Acetonitrile was
      selected as the organic solvent. Alcalase, an industrial alkaline protease, was
      applied to the synthesis of the target dipeptide. The conditions of the synthesis
      reaction were optimized by examining the effects of several factors, including
      water content, temperature, pH, molar ratio of the substrates and reaction time,
      on the yield of Bz-Arg-Gly-NH(2). The optimum conditions were established to be
      pH 10.0, 45 degrees C, in acetonitrile/0.1 M Na(2)CO(3)/NaHCO(3) buffer system
      (90:10, v/v) for 1 h with a dipeptide yield of 82.9%.

PMID- 16420190
TI  - Enzyme-linked immunosorbent assay for quantitative determination of capsular
      polysaccharide production in Streptococcus pneumoniae clinical isolates.
AB  - A simple, specific, sensitive and reproducible ELISA has been developed to
      quantify the level of CPS (capsular polysaccharide) production in supernatants of
      Streptococcus pneumoniae cell cultures. CPSs from Strep. pneumoniae have been
      widely used as vaccine antigens. The quantification method is based on two type
      23F serotype-specific polyclonal antibodies: IgG, purified from sera of mice
      immunized with a pneumococcal type-23F CPS conjugate, used in the coating step,
      and a serotype-specific rabbit serum as the second antibody. Solutions of
      purified type-23F CPS were used as standards. The relationship between A(492) and
      type-23F CPS concentration was linear over the range 1-310 ng/ml (r=0.989), with
      1 ng/ml as the lower limit of sensitivity. The specificity of ELISA was assessed
      because purified type-19F CPS and cell-wall polysaccharide samples were not
      detected after their evaluation by the ELISA described in the present study.
      Repeatability and intermediate precision of the assay were good, the coefficients
      of variation being 3 and 10% respectively. This ELISA allowed selection of an
      appropriate vaccine strain, for a natural polysaccharide vaccine, among several
      23F pneumococcal clinical isolates and constituted a valuable analytical tool for
      Strep. pneumoniae fermentation and CPS purification follow-up.

PMID- 16420191
TI  - Supplements to medical journals: adding knowledge or subtracting from the public
      trust?

PMID- 16420192
TI  - Cognitive, extrapyramidal, and magnetic resonance imaging predictors of
      functional impairment in nondemented older community dwellers: the Sydney Older
      Person Study.
AB  - OBJECTIVES: To identify the clinical correlates of functional incapacity in the
      community living "old-old." DESIGN: Cross-sectional. SETTING: Community-based.
      PARTICIPANTS: One hundred six nondemented people aged 80 to 94. MEASUREMENTS:
      Participants were medically and cognitively assessed, underwent magnetic
      resonance imaging scanning (MRI), and were interviewed regarding their functional
      status: activities of daily living (ADLs), instrumental ADLs (IADLs), and the
      complex IADL functions of reading, hobbies, and socializing. RESULTS: Dependency
      in IADLs, but not ADLs, was present. After controlling for age, sex, and
      education, extrapyramidal (EP) signs were significantly associated with two of
      the three IADLs, with EP signs comprising a composite score of 10 EP signs (e.g.,
      resting tremor) and a 5-meter timed walk. Cognitive test performance on a range
      of tests was also associated with functional status. A hierarchical model
      confirmed the association between the EP signs and cognitive test performance and
      functional scores, but no "pattern" of cognitive association emerged. Hippocampal
      volume was associated with socializing. CONCLUSION: This study has shown that
      many nondemented very old people living in the community are losing capacity to
      perform IADL functions and that areas of incapacity are associated with the
      presence of EP signs and impaired cognition. These results highlight the need for
      health workers to include an assessment of EP and cognitive status in their
      evaluation of older persons living in the community, even in the context of a
      lack of dementia diagnosis. Furthermore, it signifies the need to directly
      evaluate IADL function to identify need for intervention and support if required.
      This group of old-old individuals may now be considered the "survivors" of their
      cohort, and early detection of the difficulties they are experiencing will enable
      clinicians to respond appropriately, thus providing them a higher quality of life
      for their years to come.

PMID- 16420193
TI  - Chronic low back pain in older adults: prevalence, reliability, and validity of
      physical examination findings.
AB  - OBJECTIVES: To develop a structured physical examination protocol that identifies
      common biomechanical and soft-tissue abnormalities for older adults with chronic
      low back pain (CLBP) that can be used as a triage tool for healthcare providers
      and to test the interobserver reliability and discriminant validity of this
      protocol. DESIGN: Cross-sectional survey and examination. SETTING: Older adult
      pain clinic. PARTICIPANTS: One hundred eleven community-dwelling adults aged 60
      and older with CLBP and 20 who were pain-free. MEASUREMENTS: Clinical history for
      demographics, pain duration, previous lumbar surgery or advanced imaging,
      neurogenic claudication, and imaging clinically serious symptoms. Physical
      examination for scoliosis, functional leg length discrepancy, pain with lumbar
      movement, myofascial pain (paralumbar, piriformis, tensor fasciae latae (TFL)),
      regional bone pain (sacroiliac joint (SIJ), hip, vertebral body), and
      fibromyalgia. RESULTS: Scoliosis was prevalent in those with (77.5%) and without
      pain (60.0%), but prevalence of SIJ pain (84% vs 5%), fibromyalgia tender points
      (19% vs 0%), myofascial pain (96% vs 10%), and hip pain (48% vs 0%) was
      significantly different between groups (P < .001). Interrater reliability was
      excellent for SIJ pain (0.81), number of fibromyalgia tender points (0.84), and
      TFL pain (0.81); good for scoliosis (0.43), kyphosis (0.66), lumbar movement pain
      (0.75), piriformis pain (0.71), and hip disease by internal rotation (0.56); and
      marginal for leg length (0.00) and paravertebral pain (0.39). CONCLUSION:
      Biomechanical and soft tissue pathologies are common in older adults with CLBP,
      and many can be assessed reliably using a brief physical examination. Their
      recognition may save unnecessary healthcare expenditure and patient suffering.

PMID- 16420194
TI  - Prevalence and correlates of functional disability in multiethnic elderly
      Singaporeans.
AB  - OBJECTIVES: To make comparative estimates of prevalence of late-life functional
      disability, examine sociodemographic and health correlates, investigate sex and
      ethnic differences, and estimate population attributable risk of modifiable risk
      factors. DESIGN: Population-based survey. SETTING: Multiethnic population of
      Singapore (3 million residents). PARTICIPANTS: Noninstitutionalized Chinese,
      Malay, and Indian people aged 60 and older (N=1,079) MEASUREMENTS: Functional
      disability was defined as needing help in at least one basic activity of daily
      living (ADL) task in the 10 items of the Barthel Index. Five basic ADLs (eating,
      bathing, dressing, transferring, toileting) were used to compare prevalence with
      those reported from other national surveys and with reported past prevalence
      within the country. RESULTS: The prevalence of disability in at least one of five
      ADL items (6.6% in those aged > or = 65) appeared lower than elsewhere, including
      China, but higher than reported past prevalence within the country. Functional
      disability on at least one of the 10 ADL items was independently associated with
      female sex, Indian ethnicity, older age, poor self-rated health, specific chronic
      diseases, cognitive impairment, sensory impairment, and living with others. The
      population attributable risks for leading modifiable factors were arthritis (12%)
      and cognitive impairment (14%). CONCLUSION: Lower prevalence of functional
      disability accompanies rapid aging and health transition in Singapore than in
      other countries but higher prevalence than reported past prevalence within the
      country. Associations with sociodemographic and health-related factors were
      consistent with Western studies, including unexplained sex and ethnic
      differences.

PMID- 16420195
TI  - Alcohol consumption and risk of coronary heart disease in older adults: the
      Cardiovascular Health Study.
AB  - OBJECTIVES: To evaluate several aspects of the relationship between alcohol use
      and coronary heart disease in older adults, including beverage type, mediating
      factors, and type of outcome. DESIGN: Prospective cohort study. SETTING: Four
      U.S. communities. PARTICIPANTS: Four thousand four hundred ten adults aged 65 and
      older free of cardiovascular disease at baseline. MEASUREMENTS: Risk of incident
      myocardial infarction or coronary death according to self-reported consumption of
      beer, wine, and spirits ascertained yearly. RESULTS: During an average follow-up
      period of 9.2 years, 675 cases of incident myocardial infarction or coronary
      death occurred. Compared with long-term abstainers, multivariate relative risks
      of 0.90 (95% confidence interval (CI)=0.71-1.14), 0.93 (95% CI=0.73-1.20), 0.76
      (95% CI=0.53-1.10), and 0.58 (95% CI=0.39-0.86) were found in consumers of less
      than one, one to six, seven to 13, and 14 or more drinks per week, respectively
      (P for trend=.007). Associations were similar for secondary coronary outcomes,
      including nonfatal and fatal events. No strong mediators of the association were
      identified, although fibrinogen appeared to account for 9% to 10% of the
      relationship. The associations were statistically similar for intake of wine,
      beer, and liquor and generally similar in subgroups, including those with and
      without an apolipoprotein E4 allele. CONCLUSION: In this population, consumption
      of 14 or more drinks per week was associated with the lowest risk of coronary
      heart disease, although clinicians should not recommend moderate drinking to
      prevent coronary heart disease based on this evidence alone, because current
      National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older
      adults limit alcohol intake to one drink per day.

PMID- 16420196
TI  - A nonpharmacological intervention to improve sleep in nursing home patients:
      results of a controlled clinical trial.
AB  - OBJECTIVES: To improve nighttime sleep in nursing home patients. DESIGN:
      Controlled clinical trial. SETTING: Eight community nursing homes enrolled two at
      a time. PARTICIPANTS: Of 1,077 patients assessed in the eight nursing homes, 638
      (59%) were eligible, and consent was obtained for 273 (43% of those eligible). Of
      the 230 who underwent baseline assessments, 173 completed the immediate
      intervention phase of the trial (77 in the intervention group and 96 in the
      control group). A total of 160 subjects completed the intervention (77 in the
      immediate-intervention group and 83 in the delayed-intervention phase).
      INTERVENTION: Trained research staff provided the intervention, which included
      daytime physical activity and attempts to keep subjects out of bed, evening
      bright light exposure, a consistent bedtime routine, nighttime care routines
      designed to minimize sleep disruption, and strategies to reduce nighttime noise.
      Subjects from one nursing home received the intervention (Group 1), whereas
      subjects in the second nursing home served as a control group (Group 2); then
      Group 2 received the intervention. MEASUREMENTS: Primary outcomes included
      measures of sleep recorded using wrist actigraphy in all subjects and
      polysomnography in a subgroup of subjects. Secondary measures included
      assessments of mood and behavior using the Neuropsychiatric Inventory, the
      Geriatric Depression Scale, and behavioral observations. RESULTS: There were no
      significant differences in any of the primary actigraphic sleep outcome measures
      between the intervention and control group after the immediate-intervention phase
      of the trial. In the 160 subjects who completed the intervention, there were no
      significant changes in any actigraphic measure of nighttime sleep, nor were there
      any significant changes in measures of sleep in the 45 subjects who had baseline
      and intervention polysomnography. CONCLUSION: This multicomponent,
      nonpharmacological intervention conducted by trained research staff had no effect
      on nighttime sleep in this sample of nursing home patients. Enhanced
      nonpharmacological interventions should be developed and tested and combined with
      environmental interventions to mitigate noise when feasible. Adjunctive drug
      therapy may be needed to improve sleep in a substantial proportion of this
      population and should be tested in addition to nonpharmacological interventions
      in rigorous clinical trials.

PMID- 16420197
TI  - Prospective multicenter study of acute asthma in younger versus older adults
      presenting to the emergency department.
AB  - OBJECTIVES: To describe acute asthma in younger versus older adults presenting to
      the emergency department (ED). DESIGN: Prospective cohort study. Asthmatic adults
      were divided into three age groups: 18 to 34, 35 to 54, and 55 and older. The
      analysis was restricted to never smokers and smokers with fewer than 10 pack
      years. SETTING: ED. PARTICIPANTS: Two thousand sixty-four patients aged 18 and
      older with a physician diagnosis of asthma. MEASUREMENTS: Medications and peak
      expiratory flow. RESULTS: There were 1,158 (56%) subjects aged 18 to 34; 777
      (37%) aged 35 to 54; and 129 (6%) aged 55 and older. Older patients were most
      likely to have a primary care provider (65%, 74%, and 91%, respectively; P<.001);
      most were not taking inhaled corticosteroids (39%, 55%, and 48%, respectively;
      P<.001). Older patients reported fewer ED visits for asthma (2, 2, and 1,
      respectively; P=.001) but were more likely to report asthma hospitalization (24%,
      31%, and 37%, respectively; P<.001). All groups had severe exacerbations (initial
      percentage predicted peak flow: 47, 47, and 47, respectively; P=.50), but older
      patients were least likely to report severe symptoms (72%, 79%, and 67%,
      respectively; P=.001). Older patients did not respond as well to bronchodilators,
      even after controlling for other demographic factors, markers of asthma severity,
      and ED management (change between initial and final peak expiratory flow, using
      subjects aged 18 to 34 as reference: aged 35-54, beta=-0.7 (95% CI=-9.4-8.0);
      aged > or = 55, beta=-18.4 (-31.9 to -4.9)). The smaller change in peak
      expiratory flow contributed most to older patients' greater likelihood of
      hospitalization. CONCLUSION: Older asthma patients were less responsive to
      emergency bronchodilation. This may reflect chronic undertreatment with inhaled
      corticosteroids.

PMID- 16420198
TI  - Influence of sarcopenia on the development of physical disability: the
      Cardiovascular Health Study.
AB  - OBJECTIVES: To examine the temporal relationship between sarcopenia and
      disability in elderly men and women. DESIGN: Cardiovascular Health Study, a
      longitudinal study of cardiovascular disease and its risk factors in older
      people. SETTING: Four U.S. communities. PARTICIPANTS: Five thousand thirty-six
      men and women aged 65 and older. MEASUREMENTS: Whole-body skeletal muscle mass
      was measured at baseline, and subjects were classified as having normal muscle
      mass, moderate sarcopenia, or severe sarcopenia based on previously established
      thresholds. Disability was measured via questionnaire at baseline in up to eight
      annual follow-up examinations. The cross-sectional relationship between
      sarcopenia and prevalent disability at baseline was examined using logistic
      regression models. The longitudinal relation between sarcopenia and incident
      disability over 8 years of follow-up was examined using Cox proportional hazards
      models. RESULTS: At baseline, the likelihood of disability was 79% greater in
      those with severe sarcopenia (P<.001) but was not significantly greater in those
      with moderate sarcopenia (P=.38) than in those with normal muscle mass. During
      the 8-year follow-up, the risk of developing disability was 27% greater in those
      with severe sarcopenia (P=.006) but was not statistically greater in those with
      moderate sarcopenia (P=.23) than in those with normal muscle mass. CONCLUSION:
      Severe sarcopenia was a modest independent risk factor for the development of
      physical disability. The effect of sarcopenia on disability was considerably
      smaller in the longitudinal analysis than in the cross-sectional analysis.

PMID- 16420199
TI  - Measures of adiposity and risk of breast cancer in older postmenopausal women.
AB  - OBJECTIVES: To determine whether higher adiposity is associated with greater
      breast cancer risk in older postmenopausal women. DESIGN: Prospective cohort
      study with mean follow-up of 11.3 years. SETTING: Four U.S. clinical centers.
      PARTICIPANTS: Seven thousand five hundred twenty-three women (mean age 73.5)
      enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Weight, height,
      and waist and hip circumference were measured at baseline. Body composition was
      determined using bioelectrical impedance. Risk factor information was obtained by
      interview and questionnaire. Bone mineral density was measured using dual energy
      x-ray absorptiometry. The outcome was incident invasive breast cancer, confirmed
      using medical records. RESULTS: After adjustment for multiple risk factors,
      including bone density, women in the uppermost quartiles of weight, weight gain
      since age 25, body mass index, waist circumference, and percentage of body fat
      had higher breast cancer rates than women in the first quartiles of each measure.
      For example, breast cancer rates were 49% higher for women in the uppermost
      quartile of weight (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.05
      2.10), 64% higher for women in the top quartile of weight gain since age 25
      (HR=1.64, 95% CI=1.15-2.34), and 58% higher for women in the top quartile of
      percentage of body fat (HR=1.58, 95% CI=1.11-2.23) than for women in the lowest
      quartile of each measure. The associations between adiposity measures and breast
      cancer rates were not altered when the analyses were limited to very elderly
      women (> or = 70). CONCLUSION: Higher adiposity is an independent risk factor for
      breast cancer in elderly women.

PMID- 16420200
TI  - Simvastatin causes changes in affective processes in elderly volunteers.
AB  - OBJECTIVES: To test for simvastatin-induced changes in affect and affective
      processes in elderly volunteers. DESIGN: Randomized, clinical trial. SETTING: The
      Geriatric Behavioral Psychopharmacology Laboratory at the University of
      Pennsylvania. PARTICIPANTS: Eighty older volunteers, average age 70, with high
      normal/mildly elevated serum cholesterol. INTERVENTION: Simvastatin up to 20 mg/d
      or placebo for 15 weeks. MEASUREMENTS: Daily diary records of positive and
      negative affects and of events and biweekly measures of depressive symptoms.
      Affect ratings were obtained using the Lawton positive and negative affect
      scales; independent raters coded the valences of events. RESULTS: Thirty-one of
      39 subjects assigned to placebo and 33 of 41 receiving simvastatin completed the
      study. During biweekly assessments, four subjects on simvastatin and one on
      placebo experienced depressive symptoms, as manifest by Center for
      Epidemiological Studies Depression scale scores greater than 16 (exact P=.36).
      Diary data demonstrated significant effects on affective processes. For positive
      affect, there was a significant medication-by-time interaction that reflected
      decreases in positive affect in subjects receiving simvastatin, greatest in those
      patients whose final total cholesterol levels were below 148 mg/dL. For negative
      affect, there were significant medication-by-event, and medication-by-event-by
      time interactions, reflecting a time-limited increase in the apparent effect of
      negative events. CONCLUSION: Simvastatin has statistically significant effects on
      affect and affective processes in elderly volunteers. The decrease in positive
      affect may be significant clinically and relevant to the quality of life of many
      patients.

PMID- 16420201
TI  - Can high-risk older drivers be identified through performance-based measures in a
      Department of Motor Vehicles setting?
AB  - OBJECTIVES: To evaluate the relationship between performance-based risk factors
      and subsequent at-fault motor vehicle collision (MVC) involvement in a cohort of
      older drivers. DESIGN: Prospective cohort study. SETTING: Motor Vehicle
      Administration (MVA) field sites in Maryland. PARTICIPANTS: Of the 4,173 older
      drivers invited to participate in the study, 2,114 individuals aged 55 to 96
      agreed to do so. These analyses focus on 1,910 individuals recruited through MVA
      field sites. MEASUREMENTS: Gross Impairment Screening Battery, which included
      Rapid Pace Walk, Head/Neck Rotation, Foot Tap, Arm Reach, Cued Recall, Symbol
      Scan, Visual Closure subtest of the Motor Free Visual Perception Test (MVPT),
      Delayed Recall, and Trail Making Test with an Abbreviated Part A and standard
      Part B; Useful Field of View (UFOV) subtest 2; a Mobility Questionnaire; and MVC
      occurrence. RESULTS: In drivers aged 55 and older with intact vision (20/70 far
      visual acuity and 140 degrees visual field), age, sex, history of falls, and
      poorer cognitive performance, as measured using Trails B, MVPT, and UFOV subtest
      2, were predictive of future at-fault MVC involvement. After adjusting for annual
      mileage, participants aged 78 and older were 2.11 as more likely to be involved
      in an at-fault MVC, those who made four or more errors on the MVPT were 2.10
      times as likely to crash, those who took 147 seconds or longer to complete Trails
      B were 2.01 times as likely to crash, and those who took 353 ms or longer on
      subtest 2 of the UFOV were 2.02 times as likely to incur an at-fault MVC. Older
      adults, men, and individuals with a history of falls were more likely to be
      involved in subsequent at-fault MVCs. CONCLUSION: Performance-based cognitive
      measures are predictive of future at-fault MVCs in older adults. Cognitive
      performance, in particular, is a salient predictor of subsequent crash
      involvement in older adults. High-risk older drivers can be identified through
      brief, performance-based measures administered in a MVA setting.

PMID- 16420202
TI  - Quality of life in prostate cancer patients taking androgen deprivation therapy.
AB  - OBJECTIVES: To examine the effect of androgen deprivation therapy (ADT) on health
      related quality of life (HRQOL), self-reported HRQOL was compared in prostate
      cancer patients receiving short- (< 6 months) or long-term (> or = 6 months) ADT
      and healthy controls. DESIGN: Cross-sectional study. SETTING: Academic medical
      center in Pittsburgh, Pennsylvania. PARTICIPANTS: Ninety-six men, including those
      with prostate cancer receiving short-term, long-term, and no ADT and healthy
      controls. Men taking medications or having diseases known to affect bone mineral
      metabolism were excluded. MEASUREMENTS: The 36-item Short Form Medical Outcomes
      Study Health Survey (an HRQOL assessment) and a comorbidity index were
      administered to each participant. Characteristics, including body composition
      (assessed using dual-energy x-ray absorptiometry) and gonadal status (serum total
      and free testosterone) were measured approximately 3 months or less before the
      HRQOL assessment. RESULTS: As expected, men receiving ADT had significantly lower
      levels of testosterone, free testosterone, and lean body mass, as well as greater
      body fat and comorbidity index (all P<.01) than men not receiving ADT (i.e., men
      with prostate cancer and healthy controls). Participants receiving ADT reported
      significantly poorer QOL in the areas of physical function (P<.001), general
      health (P<.001), and physical health component summary (P<.001) than men not
      receiving ADT. There were no significant differences in HRQOL outcomes between
      participants receiving short- or long-term ADT. Comorbidity and testosterone
      levels were associated with several QOL scales. After controlling for the
      significant joint predictors of comorbidity and total testosterone using
      hierarchical regression analysis, ADT was no longer a significant predictor, and
      only comorbidity and total testosterone contributed to the explanation of the
      variance of the physical health component summary. Comorbidity alone contributed
      to the explanation of the variance in physical function, bodily pain, general
      health, and vitality. CONCLUSION: Patients with prostate cancer who were
      receiving ADT experience worse HRQOL than those not receiving ADT, but duration
      of ADT was not a contributing factor. After controlling for comorbidity, total
      testosterone level rather than ADT accounted for a small yet statistically
      significant percentage of the total variance of the physical health component
      summary. These findings have important clinical implications regarding the
      decision to treat prostate cancer patients with ADT.

PMID- 16420203
TI  - The relationship between older adults' knowledge of their drug coverage and
      medication cost problems.
AB  - OBJECTIVES: To determine whether chronically ill patients have gaps in knowledge
      about their prescription drug coverage and establish the relationship between
      gaps and medication cost problems. DESIGN: Nationwide, cross-sectional survey.
      SETTING: Nationwide survey conducted via the Internet. PARTICIPANTS: Three
      thousand one hundred nineteen adults aged 50 and older (1,400 of whom were aged >
      or = 65) who had prescription drug coverage and at least one chronic illness.
      MEASUREMENTS: Patients were asked about features of their drug benefits and
      whether they had experienced problems due to medication costs in the prior year.
      RESULTS: Twenty-five percent of respondents reported not knowing their usual
      prescription copayments, and 41% did not know whether there were caps on their
      drug coverage. Nonwhite race and lower income were independent risk factors for
      lack of knowledge about these aspects of pharmacy benefits. Lack of knowledge
      regarding the limits of coverage was associated with a greater likelihood of
      cutting back on medication use because of cost pressures, forgoing basic needs
      because of medication costs, borrowing money to pay for prescriptions, and
      worrying about medication costs (all P<.05). CONCLUSION: Many older adults with
      prescription drug coverage do not know important features of their pharmacy
      benefits. Racial minorities and those with low incomes may have the greatest
      difficulty understanding coverage and as a result may be at greatest risk for
      underusing their benefits. Education about Medicare reforms and other efforts to
      increase prescription coverage should accompany these policies.

PMID- 16420204
TI  - Cognitive function in normal-weight, overweight, and obese older adults: an
      analysis of the Advanced Cognitive Training for Independent and Vital Elderly
      cohort.
AB  - OBJECTIVES: To assess how elevated body mass index (BMI) affects cognitive
      function in elderly people. DESIGN: Cross-sectional study. SETTING: Data for this
      cross-sectional study were taken from a multicenter randomized controlled trial,
      the Advanced Cognitive Training for Independent and Vital Elderly trial.
      PARTICIPANTS: The analytic sample included 2,684 normal-weight, overweight, or
      obese subjects aged 65 to 94. MEASUREMENTS: Evaluation of cognitive abilities was
      performed in several domains: global cognition, memory, reasoning, and speed of
      processing. Cross-sectional association between body weight status and cognitive
      functions was analyzed using multiple linear regression. RESULTS: Overweight
      subjects had better performance on a reasoning task (beta=0.23, standard error
      (SE)=0.11, P=.04) and the Useful Field of View (UFOV) measure (beta=-39.46,
      SE=12.95, P=.002), a test of visuospatial speed of processing, after controlling
      for age, sex, race, years of education, intervention group, study site, and
      cardiovascular risk factors. Subjects with class I (BMI 30.0-34.9 kg/m2) and
      class II (BMI>35.0 kg/m2) obesity had better UFOV measure scores (beta=-38.98,
      SE=14.77, P=.008; beta=-35.75, SE=17.65, and P=.04, respectively) in the
      multivariate model than normal-weight subjects. The relationships between BMI and
      individual cognitive domains were nonlinear. CONCLUSION: Overweight participants
      had better cognitive performance in terms of reasoning and visuospatial speed of
      processing than normal-weight participants. Obesity was associated with better
      performance in visuospatial speed of processing than normal weight. The
      relationship between BMI and cognitive function should be studied prospectively.

PMID- 16420205
TI  - Comorbidity profile of dementia patients in primary care: are they sicker?
AB  - OBJECTIVES: To compare the medical comorbidity of older patients with and without
      dementia in primary care. DESIGN: Cross-sectional study. SETTING: Wishard Health
      Services, which includes a university-affiliated, urban public hospital and seven
      community-based primary care practice centers in Indianapolis. PARTICIPANTS:
      Three thousand thirteen patients aged 65 and older attending seven primary care
      centers in Indianapolis, Indiana. MEASUREMENTS: An expert panel diagnosed
      dementia using International Classification of Diseases, 10th Revision, criteria.
      Comorbidity was assessed using 10 physician-diagnosed chronic comorbid conditions
      and the Chronic Disease Score (CDS). RESULTS: Patients with dementia attending
      primary care have on average 2.4 chronic conditions and receive 5.1 medications.
      Approximately 50% of dementia patients in this setting are exposed to at least
      one anticholinergic medication, and 20% are prescribed at least one psychotropic
      medication. After adjusting for patients' age, race, and sex, patients with and
      without dementia have a similar level of comorbidity (mean number of chronic
      medical conditions, 2.4 vs 2.3, P=.66; average CDS, 5.8 vs 6.2, P=.83).
      CONCLUSION: Multiple medical comorbid conditions are common in older adults with
      and without dementia in primary care. Despite their cholinergic deficit, a
      substantial proportion of patients with dementia are exposed to anticholinergic
      medications. Models of care that incorporate this medical complexity are needed
      to improve the treatment of dementia in primary care.

PMID- 16420206
TI  - Outcome of critically ill oldest-old patients (aged 90 and older) admitted to the
      intensive care unit.
AB  - OBJECTIVES: To compare the outcomes of critically ill oldest-old patients (> or =
      90) with those of younger patients. DESIGN: Prospective cohort study. SETTING:
      General intensive care unit (ICU) of a tertiary care hospital in Athens, Greece.
      PARTICIPANTS: The oldest-old and younger patients. MEASUREMENTS: In-hospital and
      ICU mortality and stay, demographics, comorbidity, and complications. RESULTS: Of
      5,505 consecutive patients admitted to the ICU, 60 (1.1%) were in the oldest-old
      group (aged 90-98). Their mean length of ICU and hospital stay+/-standard
      deviation was 5.3+/-6.8 and 23.3+/-35.7 days, respectively. ICU mortality was
      20%. Total in-hospital mortality was 40%, compared with 8.9% (P=.001) in younger
      patients. Acute Physiology and Chronic Health Evaluation II score was
      independently associated with in-hospital mortality (odds ratio=1.18, 95%
      confidence interval=1.05-1.33). Of 24 oldest-old patients who died, 22 (91.7%)
      died in the ICU or in the ward within 30 days after ICU discharge. CONCLUSION:
      All-cause in-hospital mortality was higher in the oldest-old group than in
      younger patients, but the mortality of this cohort of patients did not seem to
      reach a figure that would make physicians, relatives, and healthcare
      administrators decide against ICU care in this population.

PMID- 16420207
TI  - Characteristics and outcomes of older adults with community-acquired pneumococcal
      bacteremia.
AB  - OBJECTIVES: To describe baseline characteristics and clinical outcomes of older
      adults with pneumococcal bacteremia, compare the frequency of serious outcomes
      according to pneumococcal vaccination status, and assess factors associated with
      mortality. DESIGN: Population-based case-series. SETTING: Group Health
      Cooperative, a health maintenance organization in Washington State. PARTICIPANTS:
      Community-dwelling adults aged 65 and older with a first episode of pneumococcal
      bacteremia between 1988 and 2002. MEASUREMENTS: Demographic characteristics,
      underlying medical conditions, vaccination status, and clinical outcomes,
      including death, hospitalization, length of hospital stay, and postdischarge
      care, were assessed using chart review. RESULTS: The mean age of the 200 elderly
      patients with pneumococcal bacteremia was 78; 61% were female. Forty percent had
      had chart-documented pneumococcal vaccination before the onset of bacteremia. The
      spectrum of clinical severity and consequences was broad. Ten percent were
      treated as outpatients. Of the 90% who were hospitalized, 16% were admitted to
      the intensive care unit. All-cause mortality at 30 days was 11%. Of survivors,
      23% were discharged with home services, and another 20% were discharged to a
      nursing home. After controlling for age, sex, and pneumococcal vaccination
      status, predictors of death included coronary artery disease (odds ratio
      (OR)=4.6, 95% confidence interval (CI)=1.4-14.5) and immunocompromising
      conditions (OR=5.0, 95% CI=1.6-15.7). Outcomes were similar in patients who did
      and did not receive pneumococcal vaccination. CONCLUSION: In this elderly group,
      pneumococcal bacteremia was associated with substantial morbidity, mortality, and
      loss of independence. Coronary artery disease and immunocompromising conditions
      were independent predictors of death.

PMID- 16420208
TI  - Predicting driving cessation over 5 years in older adults: psychological well
      being and cognitive competence are stronger predictors than physical health.
AB  - OBJECTIVES: To examine psychological, medical, and sensorimotor risk factors that
      predict driving cessation in older adults. DESIGN: Prospective cohort study
      including five waves of data collected in 1992, 1993, 1994, 1995, and 1997.
      SETTING: The Australian Longitudinal Study of Aging. PARTICIPANTS: One thousand
      four hundred sixty-six men and women aged 70 and older drawn from the electoral
      roll and including 753 drivers at baseline. MEASUREMENTS: Interviews, including
      assessments of self-rated health (indicating general well-being); medical
      conditions; driving status; and clinical assessments of vision, hearing,
      cognitive function, and grip strength, were conducted in 1992 (baseline) and
      1994. Information on current driving status was obtained at baseline and four
      subsequent waves (1993, 1994, 1995, and 1997). Drivers and nondrivers were
      compared at baseline. Risk factors for driving cessation were identified using
      logistic regression. RESULTS: Drivers were younger and more likely to be male and
      had better self-rated health, vision, hearing, and cognitive performance than
      nondrivers at baseline. Seventeen percent of drivers in the study had vision of
      6/18 or worse, and 7.3% were classified as possibly cognitively impaired. In
      those identified as drivers at baseline, subsequent cessation was associated with
      increasing age, low grip strength, poorer cognitive performance, and poorer self
      rated health. CONCLUSION: Self-rated health and cognitive function were more
      important than medical conditions or sensory function for predicting driving
      cessation.

PMID- 16420210
TI  - Home automated external defibrillators in a geriatric population: a brief
      discussion of the evidence.
AB  - The literature has identified significant successes in cardiac resuscitation with
      the use of automated external defibrillators (AEDs) in public areas. As of
      September 2004, the Food and Drug Administration has authorized the purchase of
      these devices by the general public without a prescription. For the practicing
      geriatrician attempting to understand the utility of these devices in a geriatric
      population, this article reviews the relevant literature of cardiac resuscitation
      and AEDs, with special attention to large public access trials.

PMID- 16420209
TI  - Estimating cardiorespiratory fitness in well-functioning older adults: treadmill
      validation of the long distance corridor walk.
AB  - OBJECTIVES: To determine criterion validity of the 400-m walk component of the
      Long Distance Corridor Walk (LDCW) and develop equations for estimating peak
      oxygen consumption (VO2) from 400-m time and factors intrinsic to test
      performance (e.g., heart rate (HR) and systolic blood pressure (SBP) response) in
      older adults. DESIGN: Cross-sectional validation study. SETTING: Gerontology
      Research Center, National Institute on Aging, Baltimore, Maryland. PARTICIPANTS:
      Healthy volunteers (56 men and 46 women) aged 60 to 91 participating in the
      Baltimore Longitudinal Study of Aging between August 1999 and July 2000.
      MEASUREMENTS: The LDCW, consisting of a 2-minute walk followed immediately by a
      400-m walk "done as quickly as possible" over a 20-m course was administered the
      day after maximal treadmill testing. HR and SBP were measured before testing and
      at the end of the 400-m walk. Weight, height, activity level, perceived effort,
      and stride length were also acquired. RESULTS: Peak VO2 ranged from 12.2 to 31.1
      mL oxygen/kg per minute, and 400-m time ranged from 2 minutes 52 seconds to 6
      minutes 18 seconds. Correlation between 400-m time and peak VO2 was -0.79. The
      estimating equation from linear regression included 400-m time (partial
      coefficient of determination (R2)=0.625), long versus short stride (partial
      R2=0.090), ending SBP (partial R2=0.019), and a correction factor for fast 400-m
      time (<240 seconds; partial R2=0.020) and explained 75.5% of the variance in peak
      VO2 (correlation coefficient=0.87). CONCLUSION: A 400-m walk performed as part of
      the LDCW provides a valid estimate of peak VO2 in older adults. Incorporating low
      cost, safe assessments of fitness in clinical and research settings can identify
      early evidence of physical decline and individuals who may benefit from
      therapeutic interventions.

PMID- 16420211
TI  - Oral care provided by certified nursing assistants in nursing homes.
AB  - The purpose of this study was to describe the actual daily oral care provided by
      certified nursing assistants (CNAs) for dentate elderly nursing home (NH)
      residents who required assistance with oral care. The study was conducted in five
      nonrandomly selected NHs in upstate New York using real-time observations of CNAs
      providing morning care to residents, retrospective chart review, and CNA
      screening interviews. Oral care standards developed and validated by a panel of
      10 experts (dentists, dental hygienists, registered nurses) to be appropriate for
      dentate NH residents were used to evaluate the oral care provided by 47 primary
      dayshift CNAs to a convenience sample of 67 residents. CNAs were blinded to the
      study's specific focus on oral care. Adherence to individual standards was low,
      ranging from a high of 16% to a low of 0%. Teeth were brushed and mouths rinsed
      with water in 16% of resident observations. One resident had her tongue brushed.
      Standards never met were brushing teeth at least 2 minutes, flossing, oral
      assessment, rinsing with mouthwash, and wearing clean gloves during oral care.
      Most residents (63%) who received oral care assistance were resistive to CNA
      approaches. For most observations, oral care supplies were not evident. Actual
      oral care provided to residents contrasts sharply with CNAs' self-reported
      practices in the literature and suggests that NH residents who need assistance
      receive inadequate oral health care.

PMID- 16420212
TI  - Ten years' experience conducting the Aging Game workshop: was it worth it?
AB  - In the Aging Game, medical students experience simulated physical, sensory, and
      cognitive deficits that are associated with disability from chronic diseases.
      Since 1994, the University of Minnesota has presented an innovative version of
      the Aging Game as part of the curriculum in a required clinical clerkship. The
      experiences conducting the Aging Game over the past decade were reviewed,
      focusing on the resources necessary to produce it and on its worth as an
      educational tool. Because many of the reusable props were obtained free as
      donations, start-up material costs were calculated at 530 dollars. Personnel
      necessary for each half-day presentation of the Aging Game included two faculty
      and a minimum of five nonfaculty serving as facilitators; a staff coordinator was
      also essential. Quantitative student evaluations (N=673) exhibited mean ratings
      of 1.41, 1.35, and 1.40 (1=excellent) for overall value, teaching effectiveness,
      and quality of a postsimulation discussion. Written student comments regarding
      the strengths of the Aging Game centered on three major themes: mode of learning,
      especially using role playing and simulating deficits (total of 192 comments);
      attitudinal change, specifically raising awareness and stimulating reflection on
      the experiences of disabled older adults (121 comments); and educational value,
      particularly the Aging Game's capacity for creating a memorable impression (56
      comments). Despite consuming significant personnel resources, the Minnesota
      version of the Aging Game is an effective tool for stimulating long-lasting
      awareness and understanding of key issues related to aging and geriatrics.

PMID- 16420213
TI  - Racial/ethnic preferences, sex preferences, and perceived discrimination related
      to end-of-life care.
AB  - This study investigated racial/ethnic preferences, sex preferences, and perceived
      discrimination related to end-of-life care. Ten focus groups and a follow-up
      survey were conducted to obtain in-depth information on end-of-life preferences
      across five racial/ethnic groups in Michigan stratified by sex. There were 73
      focus group participants, including Arab Muslims, Arab Christians, Hispanics,
      blacks, and whites. The mean age+/-standard deviation was 67+/-8.5 (range 50-83).
      A focus group screener was used to recruit participants. A moderator discussion
      guide was used to guide the focus groups. A take-home questionnaire asked about
      demographic information and end-of-life issues. Arab Americans were in favor of
      making peace on earth and were against assisted suicide, extending life
      artificially, nursing homes, and telling the patient "bad news." Hispanic and
      black women were against assisted suicide and in favor of extending life, whereas
      the men in these groups felt the opposite. Hispanic women spoke of not wanting a
      feeding tube and would consider alternative medicine. Blacks were least opposed
      to nursing homes. For whites, it was important to have choices. When asked about
      discrimination related to end-of-life care, Muslim women spoke of cultural
      barriers, blacks spoke of inequities in the past, and whites spoke of age
      discrimination and abandonment when dying. As the population becomes more diverse
      and continues to age, it will be important to provide culturally and sex
      sensitive end-of-life interventions to increase patient/family satisfaction and
      allocate resources appropriately.

PMID- 16420214
TI  - Guidelines abstracted from the Department of Veterans Affairs/Department of
      Defense clinical practice guideline for the management of stroke rehabilitation.
AB  - OBJECTIVES: To assist facilities in identifying those evidence-based processes of
      poststroke care that enhance measurable patient outcomes. The guideline(s) should
      be used by facilities (hospitals, subacute-care units and providers of long-term
      care) to implement a structured approach to improve rehabilitative practices and
      by clinicians to determine best interventions to achieve improved patient
      outcomes. OPTIONS: The guideline considers five elements of poststroke
      rehabilitation care: interdisciplinary teams; use of standardized assessments;
      intensity, timing, and duration of therapy; involvement of patients' families and
      caregivers in decision-making; and educational interventions for patients,
      families, and caregivers. Evidence, benefits, harms, and recommendations for each
      of the five designated elements and specific annotated recommendations for
      poststroke managements are presented separately. OUTCOMES: The overall guideline
      considers improvement in functional status measures as the primary outcome.
      Achieving community-dwelling status and preventing complications, death, and
      rehospitalization are also important outcomes. Costs are not specifically
      addressed. PARTICIPANTS: The Department of Veterans Affairs/Department of Defense
      (VA/DoD) Stroke Rehabilitation Working Group consisted of 28, largely VA and
      military hospital, representatives of medical and allied professions concerned
      with stroke diagnosis, management, and rehabilitation. Nine additional members
      with similar credentials served as the editorial committee. Technical
      consultation was contracted from ACS Federal Health Care, Inc., and the Center
      for Evidence-Based Practice, State University of New York-Upstate Medical
      University, Department of Family Medicine conducted evidence appraisal. Consensus
      was achieved over several years of facilitated group discussion and iterative
      evaluation of draft documents and supporting evidence. SPONSOR: The guideline was
      prepared under the auspices of the VA/DoD. No other source of support was
      identified in the document, or supporting documents.

PMID- 16420215
TI  - Mild cognitive impairment and functional status.

PMID- 16420216
TI  - Are you health-insurance literate? A question for physicians.

PMID- 16420217
TI  - Losing a matriarch.

PMID- 16420219
TI  - Advertising the new hypnotics.

PMID- 16420220
TI  - Megestrol acetate for geriatric anorexia/cachexia.

PMID- 16420222
TI  - Megestrol acetate use for anorexia in the older subject.

PMID- 16420223
TI  - Atypical antipsychotic medications and risk of falls.

PMID- 16420224
TI  - Angiotensin-converting enzyme inhibitors and pneumonia in elderly patients with
      intracerebral hemorrhage.

PMID- 16420226
TI  - Anticoagulation of atrial fibrillation in older people: a clinical practice
      observational study.

PMID- 16420227
TI  - Outbreak of human metapneumovirus infection in elderly inpatients in Japan.

PMID- 16420228
TI  - Mild behavioral impairment: a prodromal stage of frontotemporal lobar
      degeneration.

PMID- 16420229
TI  - Should aspirin be discontinued for diagnostic lumbar puncture?

PMID- 16420230
TI  - Repeated episodes of paralytic ileus in an elderly diabetic patient treated with
      voglibose.

PMID- 16420231
TI  - Giant left atrium mimicking a right thoracic mass: case report.

PMID- 16420232
TI  - Older adults' views of "successful aging": comparison of older Japanese and
      Americans.

PMID- 16420233
TI  - Depression in older adults: the case of an 82-year-old woman with dizziness.

PMID- 16420234
TI  - Carotid sinus syndrome: looking sideways is sufficient cause for syncope.

PMID- 16420236
TI  - Alpha-adrenoceptors are a common denominator in the pathophysiology of erectile
      function and BPH/LUTS--implications for clinical practice.
AB  - A literature search of PubMed documented publications and abstracts from
      proceedings of scientific meetings was made to review the available data on
      benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile
      dysfunction (ED) with a special focus on the role of alpha-adrenoceptors as
      critical mediators of pathophysiology. The reader is introduced to clinical
      results on the therapeutic potential of alpha-blockers alone and in combination
      with phosphodiesterase type 5 (PDE-5) inhibitors in the treatment of ED
      associated with LUTS/BPH. Epidemiological studies clearly show that an
      association exists between ED and LUTS/BPH. The severity of LUTS is correlated
      with the risk for ED. A significant number of LUTS/BPH patients are nonresponsive
      to the common ED treatment with PDE-5 inhibitors. As smooth muscle contractility
      is regulated by adrenoceptors in the corpus cavernosum, prostate and detrusor,
      the alpha-adrenoceptor system may be considered a common pathophysiological
      mediator in the development of ED and LUTS/BPH. Blockade of alpha-adrenoceptors
      for the treatment of BPH/LUTS may have the potential of improving sexual
      function. Conversely, PDE-5 inhibitors may exhibit positive effects in LUTS
      patients. Pilot studies on combination regimens of alpha-adrenoceptor antagonists
      and PDE-5 inhibitors have yielded encouraging results in LUTS patients with
      persistent ED. On the basis of pharmacological and clinical evidence, it is
      established that the alpha-adrenoceptor system plays an important role in the
      pathophysiology of ED and LUTS secondary to BPH. Larger trials on the combination
      of alpha-adrenoceptor antagonists with PDE-5 inhibitors are necessary to develop
      an integrated treatment approach for BPH/LUTS patients with comorbid ED.

PMID- 16420237
TI  - A Doppler-based study on the prevalence of varicocele in German children and
      adolescents.
AB  - The prevalence of varicocele was estimated among pupils of forms 4 and 8 in the
      city of Hamburg and the severity of the associated venous reflux was analysed. In
      the school year of 1998/99, a genital examination was performed on 2756 children
      (median age 10.2 years) and 2008 adolescents (14.6 years). The varicocele degree
      was determined according to the WHO. Venous reflux was proven by CW-Doppler
      sonography, distinguishing between Valsalva-induced reflux (VR) and continuous
      reflux (CR). As a result, varicoceles were detected in 18.0% of the children
      (1.2% bilaterally) and 42.7% of the adolescents (7.2%). High-graded forms
      (palpable/visible) occurred with increasing rate (from 7% to 22.9%) on the left
      side. Subtle forms (subclinical/during Valsalva) counted for >90% of all right
      sided findings, whilst an age-related shift towards higher degrees was noted left
      sided. VR occurred bilaterally, CR was almost only established left-sided. VR was
      mainly associated with subtle varicoceles, CR was predominantly found in the high
      graded forms. These results suggest that even in children varicoceles are not a
      rare phenomenon. However, adolescence is the main period of manifestation. A
      major venous malfunction is already evident in maturing boys, which seems to be
      associated with the formation of high-graded varicoceles.

PMID- 16420238
TI  - Semen quality and sperm functional parameters in fertile Indian men.
AB  - The reports of a decline in the reproductive health of men worldwide prompted the
      present study to be undertaken so that baseline semen parameters could be
      established in Indian men. Semen profile and sperm function parameters were
      evaluated in 368 Indian men of proven fertility, settled in Delhi. The results of
      the study were compared with available published information from Indian men. The
      mean sperm concentration and semen volumes were 68.22 +/- 15.14 x 10(6) ml(-1)
      and 3.20 +/- 0.94 ml, respectively. Rapid, linear progressive motility and
      sluggish linear motility were 40.95 +/- 9.15% and 24.95 +/- 7.01%, respectively.
      A comparison of the results of the present study with earlier published data did
      not support the contention of a decrease in the semen quality in Indian men.

PMID- 16420239
TI  - Epididymal stereocilia in semen of infertile men: evidence of chronic
      epididymitis?
AB  - As free stereocilia in semen samples from infertile men could be related to a
      subclinical chronic infection of the seminal tract, we carried out a
      retrospective analysis of 14 files of infertile men with stereocilia in semen
      (group 1) and in two control groups: 30 infertile men from the same study
      population (group 2) and 40 fertile sperm donors (group 3). Clinical,
      bacteriological, sonographic and microscopic findings associated with these semen
      samples were compared. Epididymal cysts were found in two of 14 men in group 1
      and in four of 28 in group 2. Positive semen cultures for Chlamydia trachomatis,
      Mycoplasma hominis or Ureaplasma urealyticum (chi(2) = 8.20; P = 0.002; OR: 7.22)
      and varicocele (chi(2) = 8.96; P = 0.002; OR: 2.25) were associated to the
      presence of free stereocilia in semen. These data suggest that a silent chronic
      infection of the epididymis by C. trachomatis, M. hominis, U. urealyticum and/or
      inflammation produced by varicocele might be the cause of stereocilia loss in the
      semen.

PMID- 16420240
TI  - Recurrent painful unilateral gynaecomastia-interactions between hyperthyroidism
      and hypogonadism.
AB  - We report an unusual case of recurrent, painful, unilateral gynaecomastia (GM) in
      an elderly male with relapsing Graves' hyperthyroidism and co-existing primary
      hypogonadism. This patient presented to the Breast Clinic with a 4-month history
      of painful, right GM. Malignancy was excluded but T3 was noted to be raised at
      7.3 pmol l(-1) (normal 3.5-5.5) with a suppressed thyroid-stimulating hormone.
      Testosterone, luteinizing hormone and follicle-stimulating hormone were
      consistent with primary hypogonadism. He was later referred to physicians with
      night sweats and painful right GM. FT3 was 7.4 and carbimazole was commenced.
      Within 4 months, the night sweats and right GM had resolved but he became
      hypothyroid. When carbimazole was stopped, right GM recurred together with
      hyperthyroidism. The male breast, which is sensitive to subtle changes in T/E2
      ratio, is more likely to be stimulated in an elderly male with hyperthyroidism
      and pre-existing hypogonadism, and hence recurrence of GM with relapsing
      hyperthyroidism. Recognition of this association is clinically relevant to avoid
      unnecessary investigations and undue patient anxiety, and to facilitate
      appropriate early diagnosis and treatment.

PMID- 16420241
TI  - Dramatic improvement of penile venous leakage upon testosterone administration. A
      case report and review of literature.
AB  - The main effect of testosterone was long-time assumed to be on sexual interest
      and, indirectly, on erectile function. Newer insights demonstrate that
      testosterone deficiency impairs the anatomical, ultrastructural, biological and
      physiological/functional substrate of penile erection, which can be, at least in
      part, restored by normalization of plasma testosterone levels. This is a report
      on a 56-year-old man suffering from diabetes mellitus type II and metabolic
      syndrome, who had complaints of a severe erectile dysfunction because of venous
      leakage, confirmed by pharmaco-cavernosography. He was also testosterone
      deficient (1.8 ng ml(-1)). Upon testosterone administration his erectile function
      improved dramatically. Repeated cavernosography no longer showed venous leakage.

PMID- 16420243
TI  - Tyrosinase maturation through the mammalian secretory pathway: bringing color to
      life.
AB  - Tyrosinase has been extensively utilized as a model substrate to study the
      maturation of glycoproteins in the mammalian secretory pathway. The visual nature
      of its enzymatic activity (melanin production) has facilitated the identification
      and characterization of the proteins that assist it becoming a functional enzyme,
      localized to its proper cellular location. Here, we review the steps involved in
      the maturation of tyrosinase from when it is first synthesized by cytosolic
      ribosomes until the mature protein reaches its post-Golgi residence in the
      melanosomes. These steps include protein processing, covalent modifications,
      chaperone binding, oligomerization, and trafficking. The disruption of any of
      these steps can lead to a wide range of pigmentation disorders.

PMID- 16420244
TI  - Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle
      function.
AB  - The Hermansky-Pudlak syndrome (HPS) is a collection of related autosomal
      recessive disorders which are genetically heterogeneous. There are eight human
      HPS subtypes, characterized by oculocutaneous albinism and platelet storage
      disease; prolonged bleeding, congenital neutropenia, pulmonary fibrosis, and
      granulomatous colitis can also occur. HPS is caused primarily by defects in
      intracellular protein trafficking that result in the dysfunction of intracellular
      organelles known as lysosome-related organelles. HPS gene products are all
      ubiquitously expressed and all associate in various multi-protein complexes, yet
      HPS has cell type-specific disease expression. Impairment of specialized
      secretory cells such as melanocytes, platelets, lung alveolar type II epithelial
      cells and cytotoxic T cells are observed in HPS. This review summarizes recent
      molecular, biochemical and cell biological analyses together with clinical
      studies that have led to the correlation of molecular pathology with clinical
      manifestations and led to insights into such diverse disease processes such as
      albinism, fibrosis, hemorrhage, and congenital neutropenia.

PMID- 16420245
TI  - Apaf-1 expression in human cutaneous melanoma progression and in pigmented nevi.
AB  - Malignant melanoma is notoriously refractive to therapy and resistant to
      apoptosis. This may reflect the downregulation of Apaf-1, an important mediator
      of mitochondrial-dependent apoptosis, observed in vitro in melanoma cell lines
      and by immunohistochemistry for Apaf-1 protein in histological samples of primary
      and metastatic melanomas. Although it has been suggested that loss of Apaf-1
      expression may be an indicator of malignant transformation in melanoma, previous
      studies on Apaf-1 expression in benign pigmented nevi were performed without
      reference to their histologic type. Here we have evaluated the expression of Apaf
      1 mRNA by fluorescence in situ hybridization and of Apaf-1 protein by
      immunohistochemistry in a large panel of human melanomas and in eight types of
      pigmented nevi, considered potential precursors for cutaneous melanoma. We
      observe a strong negative correlation between melanoma progression assessed
      according to Clark classification and the expression of Apaf-1. A significant
      decrease in Apaf-1 expression was observed between Clark II and Clark III
      lesions, the stages usually associated with a transition from horizontal to
      vertical growth phase of melanoma. There was also statistically significant
      difference in Apaf-1 mRNA expression between melanomas of Breslow thickness <1 mm
      and >4 mm. No Apaf-1 expression could be detected in lymph node melanoma
      metastases. These results suggest that Apaf-1 expression may become a prognostic
      marker for progress of human cutaneous melanoma and further support the notion
      that loss of Apaf-1 may be an important contributory factor in the development of
      the disease.

PMID- 16420246
TI  - HLA class II haplotype DRB1*04-DQB1*0301 contributes to risk of familial
      generalized vitiligo and early disease onset.
AB  - Generalized vitiligo is a common autoimmune disorder characterized by white
      patches of skin and overlying hair caused by loss of pigment-forming melanocytes
      from involved areas. Familial clustering of vitiligo is not uncommon, and
      patients and their relatives are at increased risk for a specific complex of
      other autoimmune diseases. Compared with sporadic vitiligo, familial vitiligo is
      characterized by earlier disease onset and greater risk and broader repertoire of
      autoimmunity, suggesting a stronger genetic component, and perhaps stronger
      associations with specific alleles. To determine whether the major
      histocompatibility complex (MHC) contributes to the familial clustering of
      vitiligo and vitiligo-associated autoimmune/autoinflammatory diseases, we
      performed case-control and family-based association analyses of HLA class II-DRB1
      and -DQB1 alleles and haplotypes in affected probands and their parents from 76
      European-American Caucasian families with familial vitiligo. Affected probands
      showed a significantly increased frequency of DRB1*04-DQB1*0301 and a
      significantly decreased frequency of DRB1*15-DQB1*0602 compared with a large
      sample of reference chromosomes. Family-based association analyses confirmed
      these results. Probands with DRB1*04-DQB1*0301 developed vitiligo an average of
      13.32 yr earlier than probands with DRB1*15-DQB1*0602. Overall, our results
      indicate that specific MHC-linked genetic variation contributes to risk of
      familial vitiligo, although HLA does not completely explain familial clustering
      of vitiligo-associated autoimmune/autoinflammatory diseases.

PMID- 16420247
TI  - Glutamate receptors on human melanocytes regulate the expression of MiTF.
AB  - Glutamate is the major excitatory neurotransmitter in the central nervous system
      but has also important functions in the epidermis. It is involved in keratinocyte
      barrier function and in re-epithelialization processes after wounding. Recently,
      glutamate signalling has been suggested to be implicated in the development of
      melanoma. The present study examined the expression and functionality of
      metabotropic and ionotropic glutamate receptors on normal human melanocytes. We
      found that cultured melanocytes expressed the ionotropic glutamate receptors
      GluR2 and 4 [alpha-amino-3-hydroxy-5-methyl-4-isoxsazolepropionic acid (AMPA)
      receptors] and N-methyl-d-aspartate (NMDA) receptors 2A and 2C and possibly the
      metabotropic glutamate receptor 1. Melanocytes were also found to express
      specific glutamate transporters and decarboxylases, but appeared neither to
      produce nor to release l-glutamate. Stimulation with 10 or 100 microM AMPA or
      NMDA elevated intracellular calcium concentrations in melanocytes, and thus
      demonstrated the functionality of the glutamate receptors. Millimolar
      concentrations of l-glutamate did not induce melanocyte toxicity and had no
      stimulating effect on melanin production. However, blockage of AMPA and NMDA
      receptors with CFM-2, memantine or MK801 caused a rapid and reversible change in
      melanocyte morphology, which was associated with disorganisation of actin and
      tubulin microfilaments. After 24 h of treatment with the AMPA receptor inhibitor
      CFM-2, there was a sharp reduction in the expression of the crucial melanocyte
      differentiation and proliferation factor MiTF. The results of this study
      demonstrate a role for glutamate in melanocyte regulation that may have
      implications in melanocyte associated disorders.

PMID- 16420248
TI  - Association of kinesin and myosin with pigment granules in crustacean
      chromatophores.
AB  - Chromatic adaptation in crustaceans results from the differential distribution of
      colored pigment granules within their chromatophores consequent to cell signaling
      by neurosecretory peptides. However, the force transducing, mechanochemical
      protein motors responsible for granule translocation, and their molecular
      mechanisms of action, are not well understood. The present study uses
      immunocytochemical techniques and a motility assay in vitro to demonstrate that
      protein motors from the kinesin and myosin superfamilies are stably associated
      with membrane-bounded pigment granules in the red, ovarian chromatophores of the
      freshwater, palaemonid shrimp, Macrobrachium olfersii. Monoclonal antibodies
      against conventional kinesin heavy chain, and an anti-myosin whole serum, labeled
      pigment-containing fragments prepared from homogenates of chromatophores with
      fully dispersed or aggregated pigments: this finding infers a permanent
      association between the protein motors and the pigment granules, and suggests
      that such motors may be regulated while bound to their cargos. The pigment
      aggregator appears to be a myosin since the anti-myosin whole serum attenuated
      hormonally triggered pigment aggregation in the motility assay in vitro, and
      induced pigment hyper-dispersion in some chromatophores. Western blots of the
      chromatophore-containing, ovarian tissue homogenate demonstrated protein bands
      consistent with myosin II and myosin XII, either of which may be the pigment
      aggregator. This study provides the first direct evidence for myosin and kinesin
      protein motors directly and stably associated with pigment granules in crustacean
      chromatophores, and may represent the first successful isolation of myosin class
      XII.

PMID- 16420249
TI  - Quantitative analysis of MC1R gene expression in human skin cell cultures.
AB  - To address the issue of melanocortin-1 receptor (MC1R) expression in non
      melanocytic cells, we have quantitatively evaluated the relative expression
      levels of both MC1R mRNA and protein in a subset of different cell types. Using
      semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at
      high cycle numbers, we detected MC1R mRNA in all cell types examined, including
      human embryonic kidney-293 (HEK 293) cells, a cell type widely used as a negative
      control in melanocortin expression studies. Quantitative real-time PCR revealed
      the highest levels of MC1R transcripts were in melanocytic cells, whereas the
      keratinocyte and fibroblast cell cultures examined had only a low level of
      expression, similar to that of HEK 293 cells. Antibody mediated detection of MC1R
      protein in membrane extracts demonstrated exogenous receptor in MC1R transfected
      cell lines, as well as endogenous MC1R in melanoma cells. However, radioligand
      binding procedures were required to detect MC1R protein of normal human
      melanocytes and no surface expression of MC1R was detected in any of the non
      melanocytic cells examined. This was consistent with their low level of mRNA, and
      suggests that, if present, the levels of surface receptor are significantly lower
      than that in melanocytes. The capacity of such limited levels of MC1R protein to
      influence non-melanocytic skin cell biology would likely be severely compromised.
      Indeed, the MC1R agonist [NIe(4), D-Phe(7)] alpha-melanocyte stimulating hormone
      (NDP-MSH) was unable to elevate intracellular cyclic adenosine monophosphate
      (cAMP) levels in the keratinocyte and fibroblast cells examined, whereas a robust
      increase was elicited in melanocytes. Although there are a variety of cell types
      with detectable MC1R mRNA, the expression of physiologically significant levels
      of the receptor may be more restricted than the current literature indicates, and
      within epidermal tissue may be limited to the melanocyte.

PMID- 16420251
TI  - Analysis of genotypic and phenotypic clinical cut-off levels for ritonavir
      boosted saquinavir.
AB  - There is a need for new, clinically relevant interpretation algorithms for
      genotypic and phenotypic resistance for ritonavir-boosted saquinavir (SQV/r) at
      the current approved dosage [1000/100 mg twice a day (bid)]. Clinical cut-off
      levels, which correlate baseline measures of resistance with HIV RNA responses in
      large cohorts or clinical trials, are the ideal reference for developing such
      algorithms. Cut-off levels previously developed for unboosted saquinavir may no
      longer apply, as the plasma drug levels with SQV/r are significantly higher and
      may be able partially to overcome protease inhibitor-resistant HIV. Clinical cut
      off levels for SQV/r, assessed in several cohort studies and clinical trials,
      also suggest that multiple genotypic mutations are required for complete loss of
      virological response. For phenotypic analysis of resistance, saquinavir cut-off
      levels 10-11-fold higher than the wild-type IC50 have best distinguished
      responders from non-responders in cohort studies. Using Virtual Phenotype, a 12.3
      fold upper cut-off level was determined from analysis of large cohort databases.
      These genotypic and phenotypic algorithms need to be validated in larger
      prospective studies.

PMID- 16420250
TI  - Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell
      line by downregulation of tyrosinase expression.
AB  - Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation
      disorders are associated with abnormal accumulation of melanin pigments, which
      can be improved by treatment with depigmenting agents. In the present study,
      piperlonguminine from Piper longum was discovered to inhibit melanin production
      in melanoma B16 cells stimulated with alpha-melanocyte stimulating hormone (alpha
      MSH), 3-isobutyl-1-methylxanthine or protoporphyrin IX, where the compound
      exhibited stronger depigmenting efficacy than kojic acid. However,
      piperlonguminine did not affect 1-oleoyl-2-acetyl-sn-glycerol-induced
      melanogenesis and did not affect protein kinase C-mediated melanin production.
      Surprisingly, piperlonguminine did not inhibit the catalytic activity of cell
      free tyrosinase from melanoma B16 cells but rather suppressed tyrosinase mRNA
      expression. This effect was attributed to the inhibitory action of
      piperlonguminine on alpha-MSH-induced signaling through cAMP to the cAMP
      responsive element binding protein that in turn regulates the expression of the
      microphthalmia-associated transcription factor, a key activator of the tyrosinase
      promoter. This study demonstrates that piperlonguminine is an efficient
      depigmenting agent with a novel mechanism of action.

PMID- 16420252
TI  - nef gene sequence variation among HIV-1-infected African children.
AB  - BACKGROUND: There are few data on African children infected with nonclade B HIV-1
      in endemic settings, which limits generalizations about pathogenesis and
      progression. Genotypic and phenotypic variations in host immunogenetics and HIV-1
      negative factor (nef) accessory protein may influence disease progression and
      have frequently been characterized in subjects infected with clade B HIV-1.
      METHODS: In this descriptive study, we report nef gene sequence variation and
      host genetic polymorphisms in 32 Kenyan children, including 12 slow progressors.
      RESULTS: Phylogenetic analysis identified HIV-1 clades A, C and D and a
      recombinant A/D subtype. Grossly defective nef genes or significant changes from
      relevant clade reference sequences were not identified in children with delayed
      disease progression. CONCLUSIONS: nef sequence variations may not be common in
      perinatally infected African children. Further studies are warranted in HIV-1
      infected subjects in settings where infection is endemic.

PMID- 16420254
TI  - Immunological and virological responses to highly active antiretroviral therapy
      in a non-clinical trial setting in a developing Caribbean country.
AB  - OBJECTIVE: Few data exist on the efficacy of antiretroviral therapy in
      individuals infected with HIV in the Caribbean. We evaluated the virological and
      immunological responses of HIV-infected adults starting highly active
      antiretroviral therapy (HAART). DESIGN: This was a prospective observational
      cohort study. METHODS: A total of 158 antiretroviral-naive patients who initiated
      HAART between January 2002 and March 2003, and completed at least 6 months of
      treatment and follow up, were included in the analysis. The response to therapy
      was assessed by changes in CD4 cell counts and viral loads from baseline. The
      mean increase in CD4 cell count, the rate of virological success (a viral load of
      <50 HIV-1 RNA copies/mL) and the rate of immunological success (an increase in
      CD4 cell count of > or =50 cells/microL over the baseline value) after commencing
      HAART were measured. RESULTS: In total, 82% of patients (123 of 150) achieved
      viral loads of <50 copies/mL after 6 months of therapy. Viral success rate after
      6 months of HAART was similar irrespective of gender, pre-HAART CD4 cell count
      and pre-HAART viral load. However, patients older than 40 years were
      significantly more likely to achieve virological success than those younger than
      40 years. At 6 months after starting HAART, 79.5% of patients were estimated to
      have achieved immunological success and 17.9% had an increase in CD4 cell count
      of > or =200 cells/microL over the baseline value. The median increase in CD4
      cell count for the 156 patients who had CD4 cell counts at baseline and at 6
      months of therapy was 122 cells/microL. CONCLUSION: In this cohort of
      antiretroviral-naive HIV-infected adults, there was a high rate of virological
      and immunological success after 6 months of HAART, irrespective of the pre-HAART
      viral load and CD4 cell count.

PMID- 16420253
TI  - A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and
      lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in
      antiretroviral-naive patients: effect of sex and ethnicity.
AB  - OBJECTIVES: To compare the lipid and metabolic effects, efficacy, and safety of
      twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine
      300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300
      mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine
      (3TC)+NFV. STUDY DESIGN: An international, phase 4, open-label, parallel-group,
      34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV
      infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and <
      or =200,000 copies/mL and a CD4 cell count of >50 cells/microL. METHODS: Patients
      were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice
      daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96
      weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard
      to changes from baseline in fasting lipids in the total population and in sex and
      ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400
      copies/mL were compared using a 95% confidence interval (CI) on the difference
      between proportions. RESULTS: The study population was diverse (50% female, 40%
      black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol
      was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355
      cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV
      group [least square mean (LSM) change from baseline, -8 mg/dL], but increased
      with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus
      TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group
      than in the other two treatment groups in women and men and lower than in the
      d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96
      LSM change from baseline in LDL cholesterol was significantly less with TZV than
      with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL
      occurred in a smaller proportion of patients receiving TZV (30%) compared with
      COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein
      (HDL) cholesterol did not change markedly with any treatment. Although
      triglycerides increased, they changed least in women and Hispanic patients
      receiving TZV. Virological and CD4 responses to the treatments were similar in
      the total population and in the subgroups. Diarrhoea was reported more often in
      the NFV arms and nausea in the ZDV arms. CONCLUSIONS: Over 96 weeks, TZV twice
      daily has significantly less effect on LDL cholesterol than COM/NFV or
      d4T/3TC/NFV twice daily, especially in women and black patients, and is
      associated with similar virological and CD4 responses.

PMID- 16420255
TI  - Minor changes in calculated creatinine clearance and anion-gap are associated
      with tenofovir disoproxil fumarate-containing highly active antiretroviral
      therapy.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (Tenofovir DF, TDF), the first
      nucleotide reverse transcriptase inhibitor approved for the treatment of HIV
      disease, has been associated with renal dysfunction in isolated cases. The aim of
      this study was to assess changes in renal parameters in individuals receiving TDF
      and non-TDF-containing highly active antiretroviral therapy (HAART). METHODS:
      All individuals on HAART attending our clinic were included in the analysis. Time
      weighted changes in serum creatinine, calculated creatinine clearance (CCrCl) and
      anion-gap were assessed for individuals on TDF- and non-TDF HAART. RESULTS: Of
      948 individuals on HAART, 290 (31%) and 618 (65%) were on TDF- and non-TDF HAART,
      with 40 (4%) having ceased TDF HAART. Baseline values for serum creatinine, CCrCl
      and anion-gap were similar for those on TDF- and non-TDF HAART. In a multivariate
      analysis, statistically significant differences were observed in time-weighted
      change from baseline in anion-gap and CCrCl between individuals on TDF- and non
      TDF HAART [mean difference in change between groups: anion-gap 0.78 mmol/L
      (standard error, 0.19) and CCrCl-6.80 (standard error 2.2); P = 0.005 and P =
      0.032, respectively] after adjusting for baseline anion-gap and CCrCl,
      respectively. Two cases of TDF-associated renal failure were observed.
      CONCLUSION: Overt renal failure with TDF HAART is rare. However, subtle but
      statistically significant changes in anion-gap and CCrCl were observed which were
      associated with TDF HAART. These parameters may be of use in monitoring
      individuals on HAART.

PMID- 16420256
TI  - Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year
      follow-up.
AB  - OBJECTIVES: The aims of this study were to follow a cohort of HIV-infected
      individuals for 2 years to assess changes in depression and neuropsychological
      performance over time, to explore the relationship between depression, HIV
      illness and neuropsychological performance, and to examine the natural history of
      the effect of highly active antiretroviral therapy (HAART) on depression and
      neurocognitive performance. METHODS: HIV-seropositive out-patients were assessed
      at baseline and at 2-year follow-up. At each assessment, patients were assessed
      for depression [using the Beck Depression Inventory (BDI) and Structured Clinical
      Interview (SCID-CV)] and completed a battery of neuropsychological tests
      including the Cambridge Neuropsychological Test Automated Battery (CANTAB) and
      the Hopkins HIV Dementia Scale (HDS). RESULTS: At baseline, 34.8% scored > or =14
      on the BDI [> or =14 suggests depressive symptoms (DS)]. The SCID-CV revealed
      that 27% of participants met the criteria for current mood disorder. Seven per
      cent of the participants' scores on the HDS indicated HIV-associated cognitive
      changes. Eighty participants were re-tested at 2-year follow-up and were split
      into two groups based on BDI scores at baseline. CANTAB results revealed that the
      cohort were significantly impaired on nine of 10 measures compared with age
      matched normative data. Neurocognitive performance significantly improved for
      participants with no DS at baseline, whereas participants with DS at baseline did
      not show as much improvement. Multivariate analysis revealed that 40% of the
      change in cognitive performance was attributable to the variables age, AIDS and
      HAART regimen. CONCLUSION: These results suggest a significant decline in
      depression scores and an improvement in several neurocognitive domains over time,
      with a relationship between HIV illness, HAART, symptoms of depression and
      neurocognitive performance.

PMID- 16420257
TI  - Characterization of nelfinavir binding to plasma proteins and the lack of drug
      displacement interactions.
AB  - OBJECTIVES: To determine the characteristics of the binding of nelfinavir and
      active M8 to alpha1-acid glycoprotein (AAG) and human serum albumin (HSA), and to
      examine the displacement effects of drugs binding extensively to AAG (ritonavir
      and saquinavir) or to HSA (salicylic acid and valproic acid). METHODS: Free drugs
      were separated by equilibrium dialysis after incubation with human plasma or
      purified plasma proteins and after co-incubation with potential displacers.
      Association constants were estimated from double-reciprocal plots of the data.
      RESULTS: Nelfinavir and M8 free fractions [fractions of unbound drug (fus)] were
      0.42+/-0.08% (mean+/-standard deviation) and 0.64+/-0.07%, respectively. For the
      two analytes, respectively, association constants were 7.25 x 10(7)/m and 3.33 x
      10(7)/m for AAG and 1.11 x 10(6)/m and 7.92 x 10(5)/m for HSA. Nelfinavir fu in
      an AAG solution was significantly (P < 0.01) increased by the addition of
      ritonavir or saquinavir, whereas it was unaltered by addition of these drugs to
      whole plasma. Similarly, fu in an HSA solution was significantly increased (P <
      0.01) by the addition of salicylic acid or valproic acid, whereas there was no
      difference in the free fraction in plasma. CONCLUSIONS: The affinity of
      nelfinavir for human plasma proteins was higher than that of M8, and both
      nelfinavir and M8 showed higher affinity to AAG than to HSA. The free fraction of
      nelfinavir was not affected by drugs that bind extensively to AAG or albumin when
      these drugs were added to whole plasma in combination, suggesting a compensatory
      effect of alternate binding proteins.

PMID- 16420258
TI  - HIV-related neutropaenia exacerbated by efavirenz.

PMID- 16420259
TI  - Genetic variability in French dog breeds assessed by pedigree data.
AB  - Pedigree data of nine French dog breeds, namely Barbet (BAR), Basset fauve de
      Bretagne (BAF), Beauceron (BEN), Berger des Pyrenees (BRP), Bouledogue Francais
      (BUF), Braque Saint-Germain (BQG), Dogue de Bordeaux (DOB), Epagneul Breton (EPB)
      and Montagne des Pyrenees (MOP), were analysed. The effective numbers of
      ancestors of dogs born from 1997 to 2001 were equal to 6.7 (BAR), 40.2 (BAF),
      36.5 (BEN), 16.0 (BRP), 37.0 (BUF), 13.1 (BQG), 28.9 (DOB), 33.3 (EPB) and 34.0
      (MOP). The expected contributions of the major ancestors were found to be highly
      unbalanced in the EPB and BRP. The average coefficient of inbreeding of dogs born
      from 1997 to 2001 with both parents known was equal to 12.4% (BAR), 3.9% (BAF),
      5.4% (BEN), 7.2% (BRP), 3.3% (BUF), 6.0% (BQG), 4.1% (DOB), 4.5% (EPB) and 4.0%
      (MOP). These values were found to be significantly higher than the average
      coefficient of kinship between the male and the female parents of these animals,
      except in the BAR and BQG, revealing an usual practice of mating between related
      animals. The results are discussed in relation with the demographic situation and
      the use of each breed. The method used to class an endangered breed and the ways
      to preserve the genetic variability, when necessary, are evoked.

PMID- 16420260
TI  - Tuscany autochthonous cattle breeds: an original genetic resource investigated by
      AFLP markers.
AB  - The aim of this study was to assess the genetic diversity of four autochthonous
      cattle breeds of Tuscany and their relationships in comparison with Italian
      Friesian and Italian Brown, using amplified fragment length polymorphism markers.
      A total of 212 individuals were genotyped with three primer combinations
      generating 102 polymorphic markers. Average expected heterozygosity ranged from
      0.23 in Mucca Pisana to 0.26 in Chianina, Italian Friesian, Italian Brown and
      Maremmana. The differences resulted not significant (Kruskall-Wallis test, p =
      0.416). Gst-B index revealed that 86% of the total genetic variance is retained
      within population and only 14% is accounted by the between populations component.
      Multivariate analysis at individual and population level indicated that: (i)
      Calvana and Chianina are quite separate from the other breeds as an effect of the
      bottleneck experienced or as a signature of different origin; (ii) Podolian,
      Maremmana and Italian Brown clustered with the double purpose Mucca Pisana,
      revealing their contribution to its admixed genetic make up; (iii) Italian
      Friesian behaved always as out group. The 'analysis of molecular variance'
      recovered a significant subdivision clustering the six populations into three
      groups: Italian Friesian and Italian Brown versus Maremmana and Mucca Pisana
      versus Chianina and Calvana (6% of the total variance).

PMID- 16420261
TI  - Association of a melanocortin 4 receptor (MC4R) polymorphism with performance
      traits in Lithuanian White pigs.
AB  - The melanocortin 4 receptor is expressed in virtually all brain regions of
      mammals and plays an important role in energy homeostasis. Polymorphisms in this
      gene may thus be related to growth and obesity. In pigs, a non-synonymous
      polymorphic site was described (Asp298Asn) and demonstrated to affect cAMP
      production and to alter adenylyl cyclase signalling. Association studies revealed
      significant linkage of this mutation with production trait in pigs. In this
      study, 207 Lithuanian White pigs were genotyped at the MC4R locus and analysed on
      relationships between genotype and breeding values for several performance
      traits. The observed allele and genotype frequencies did not deviate
      significantly from Hardy-Weinberg equilibrium (wildtype allele 0.59; mutant
      allele 0.41) and are comparable with those described in other Large White
      populations. The mutant Asn298 allele of the MC4R gene was significantly
      associated with increased test daily gain, higher lean meat percentage and lower
      backfat thickness. There was a trend towards an improved feed conversion ratio (p
      = 0.065) in animals with the mutant allele whereas no significant effect was
      found on lifetime daily gain. These results indicate that the MC4R polymorphism
      should be integrated in selection programmes in the Lithuanian White to improve
      carcass composition.

PMID- 16420262
TI  - Economic values for production and functional traits and assessment of their
      influence on genetic improvement in the Boran cattle in Kenya.
AB  - Economic values for production (sale weight in steers, SWs, kg and heifers, SWh,
      kg; dressing percentage, DP; consumable meat percentage, CMP and milk yield, MY,
      kg) and functional (cow weight, CoWT, kg; cow survival rate, CoSR, %; postweaning
      survival rate, PSR, %; feed intake of cows, FIc, heifers, FIh and steers, FIs, kg
      DM) traits were estimated for six production systems utilizing the Boran breed in
      Kenya. The influence of the estimated economic values on genetic improvement was
      also assessed using different selection indices. The six production systems were
      described according to their sale age, levels of input and final goal, namely,
      short-fed medium input beef (SMB); long-fed medium input beef (LMB); short-fed
      high input beef (SHB); long-fed high input beef (LHB); long-fed low input dual
      purpose (LLD); and long-fed medium input dual purpose (LMD). Two evaluation bases
      were considered: fixed herd size and fixed pasture input. In the fixed herd-size
      situation, the economic values for production (except MY in beef systems) and
      functional traits (except FI in all systems) were positive meaning a unit
      increase in genetic merit of these traits had greater influence on revenues than
      costs. As expected, the economic value for MY was negative in the pure beef
      systems (SMB, LMB, SHB and LHB) and positive in the dual-purpose systems (LLD and
      LMD). When compared with the economic values estimated in the fixed herd-size
      situation, in the fixed pasture input situation they were lower for feed intake
      in the three classes of livestock and other traits related to it in all systems.
      These traits were CoSR, CoWR, PSR, CoWT, SWh and MY. The economic values for CoWT
      in LLD and LMD were negative (KSh -11.14 and -15.33 respectively). The economic
      values did not influence much the direction of the genetic response in each trait
      in the different production systems. However, the magnitude of the actual gain
      was dependent on the index applied. The magnitude of the economic values for
      production and functional traits estimated in this study suggest that genetic
      improvement of these traits will have a positive effect on profitability of Boran
      cows kept in dual-purpose systems and when herd size is restricted. In beef
      systems, genetic improvement of MY will have a negative effect on profitability,
      especially when restrictions on herd size and feed exists.

PMID- 16420263
TI  - Body weights at weaning and 18 months of Zebu, Brown Swiss, Charolais and
      crossbred heifers in south-east Mexico.
AB  - The objective of this study was to evaluate the body weights up to 18 months of
      age of 12 breed groups of Zebu (Z), Brown Swiss (BS) and Charolais heifers (CH),
      and their crosses under tropical conditions. A total of 1434 data on weaning
      weights adjusted to 240 days (WW8), average daily gain to 240 days (ADG8) and
      1025 body weights adjusted to 550 days (BW18) and average postweaning daily gain
      (ADG18) of heifers born from 1981 to 1995 were used. Cows and calves remained
      together from birth to weaning and grazed on Guinea grass (Panicum maximum).
      Years of birth were grouped in three periods, because of the small numbers of
      observations per year (1981-85, 1986-90 and 1991-95). Similarly, months of birth
      were grouped in three seasons: dry (February to May), rainy (June to September)
      and windy and rainy (October to January). Ages of dams were classified in six
      groups (<or=3, 4, 5, 6, 7 and >or=8 years). Breed groups were animals with 12.5%,
      25.0%, 50.0%, 62.5%, 75.0% and 100% BS genes and 25.0%, 50.0%, 75.0% and 100% CH
      genes and also Z and undefined crossbred animals. Data were analysed using a
      fixed model that included effects of period, and season of birth, age of dam and
      breed group of heifer. Analyses of variance showed significant (p < 0.05) effects
      of period, season and breed group for all traits. However, parity was significant
      (p < 0.05) only for WW8 and ADG8. Interactions among main factors were not
      significant (p > 0.05). Z heifers gained the least weight to weaning but were
      similar to BS at 18 months of age. CH were heavier at 18 months of age than BS
      heifers, but not at weaning. Body weights at 18 months of age of 1/8 and 1/4 BS
      crossbred heifers were similar (p > 0.05) and lower than F1 (BS x Z) (p < 0.05);
      however, the later and higher grades of BS had the highest body weights at 18
      months of age and were similar to CH and 1/4 CH x 3/4 Z heifers. Undefined
      crossbred heifers had better performance than the Z breed group. Environmental
      factors were important sources of variation for pre- and postweaning traits.
      Under the conditions of this study, crossbred heifers generally performed better
      than Z heifers up to 18 months of age.

PMID- 16420264
TI  - Quantitative analysis of production traits in saltwater crocodiles (Crocodylus
      porosus): III. juvenile survival.
AB  - Mortality records of 1302 juvenile crocodiles were available for analysis.
      Crocodiles that were slaughtered during this study were treated as censored (n =
      2151). Additionally, records from animals that had neither died nor been
      slaughtered, i.e. were still alive in the production system (n = 1582), were
      censored at the last date of data collection. There were a total of 3733 censored
      records. The data were all full-sib records from 29 parental pairs from Janamba
      Croc Farm (Northern Territory, Australia), collected over nine consecutive years.
      Data were analysed using an extension of Cox's proportional hazards model to
      include frailty (random) terms to account for genetic effects. Heritability of
      log survival time for juvenile crocodile survival was 0.15 (SE 0.04). The
      probability of a juvenile crocodile surviving to day 400 was estimated to be only
      51%. These results are the first to quantify juvenile survival in a captive
      breeding situation. Also, this is the first heritability estimate of crocodile
      survival and is a fundamental element in the development of a genetic improvement
      programme.

PMID- 16420265
TI  - Quantitative analysis of production traits in saltwater crocodiles (Crocodylus
      porosus): IV. number of scale rows.
AB  - A total of 3156 scale row records, comprising 1739 full-sibling records from 30
      families from Janamba Croc Farm (NT, Australia) and 1417 parent-offspring records
      from 19 families from Wildlife Management International, Pty Ltd (NT, Australia),
      collected at each facility using a different method, were analysed using ASReml.
      The full-sibling heritability estimate for the Janamba data was 0.37 (SE 0.03).
      The animal model estimate of heritability for the Wildlife Management
      International (WMI) data, also based predominantly on full-sibling data, was 0.42
      (SE 0.04). The counts from three counting methods were evaluated by regression
      analysis on 100 individuals and were found to be highly correlated. Using the
      regression relationship, the WMI data were transformed and pooled with the
      Janamba data to give an animal model heritability estimate of 0.42 (SE 0.04). A
      multitrait analysis revealed negligible correlations (both phenotypical and
      genetical) between hatchling size traits and the number of scale rows. There is
      ample genetic variation to incorporate this trait into a genetic improvement
      programme for farmed saltwater crocodiles.

PMID- 16420266
TI  - Modelling number of services per conception of Japanese Black cattle by random
      regression.
AB  - Repeated records of number of services per conception (NSC) were collected on 607
      Japanese Black cows. Data were analysed by random regression (RRM) and multiple
      trait (MTM) models, considering NSC in each parity as a separate trait. The
      chosen RRM included additive genetic and permanent environmental effects fitted
      with a third-order Legendre polynomials of parity. Heritabilities (h2) estimated
      by RRM decreased along the NSC trajectory from 0.15 in the first parity to 0.04
      in the sixth parity and then increased up to 0.22 in the 10th parity. The
      corresponding estimates obtained by MTM ranged between 0.04 in parity 9 and 0.13
      in parity 1. Permanent environmental proportions (p2) of the total phenotypic
      variance estimated by RRM showed similar pattern and magnitude to those of h2
      estimated by the same method. On the contrary, the p2 estimated by MTM ranged
      between 0.04 in the first parity and 0.11 in the 10th parity. Additive genetic
      (r(G)), permanent environmental (r(P)) and phenotypic (r(PH)) correlations were
      also estimated. The values estimated by RRM between adjacent parities were higher
      than those of parities far apart. The corresponding values estimated by MTM were
      lower than those estimated by RRM with no certain trend. The results indicated
      that NSC in heifers is more heritable than NSC in cows with different parities.
      Reproductive traits are economically important traits and hence, they should be
      considered in breeding goals.

PMID- 16420267
TI  - Use of survival analysis as a tool for the genetic improvement of age at first
      conception in Nellore cattle.
AB  - Restricted breeding seasons in beef cattle lead to censoring of reproductive
      data. In this paper, age at first conception (AFC) of Nellore females exposed to
      the sires for the first time between 11 and 16 months of age, was studied aiming
      to verify the possibility of genetically advance sexual precocity using a
      survival model. The final data set contained 6699 records of AFC in days. Records
      of females that did not calve in the next year following exposure to the sire
      were considered censored (77.5% of total). The model used was a Weibull mixed
      survival model including effects of contemporary groups, period (fixed) and
      animal (random). The effect of the contemporary groups on AFC was important (p <
      0.01). Heritabilities were 0.51 and 0.76 in logarithmic and original scales
      respectively. Results indicate that it is possible to genetically advance sexual
      precocity, using the outcome of survival analysis of AFC as selection criterion.
      They also suggest that improvements of the environment could advance sexual
      precocity too, thus an adequate pregnancy rate for farmers could quickly be
      achieved.

PMID- 16420269
TI  - Cephalometric evaluation of condylar and mandibular growth modification: a
      review.
AB  - OBJECTIVE: Based on a wealth of orthodontic archives, this work aims to review
      the cephalometric analysis systems that can identify the changes in condylar and
      mandibular position as well as growth direction in response to bite jumping
      therapy. DESIGN: Numerous cephalometric approaches were screened to testify their
      feasibility and reliability in accurately depicting the growth modification of
      the condyle and the mandible. The critical assessment of the working mechanisms
      of these cephalometric methods was elaborated to help build up the rationale and
      justification for their clinical use. RESULTS: 1) The changes in condylar and
      mandibular size, position and growth direction can be identified by using lateral
      cephalograms with closed-mouth or open-mouth posture. 2) With superimposition
      methods where the anatomical structures for superimposition registration must be
      stable and reproducible, the growth modification of the condyle and the mandible
      between two time-points is qualitatively demonstrated in a diagram if reference
      lines are not constructed. The growth modification can be quantitatively
      identified if the reference lines are created. 3) With non-superimposition
      methods, the size and position of the condyle and the mandible are separately
      identified for each time-pint by relating them to the stable reference
      structures. The growth modification between two time-pints is evaluated by
      comparing the two separate measurements. CONCLUSION: The application of a
      standardized and well designed cephalometric evaluation system may reduce the
      bias that attribute to the arbitrariness of the clinical effects of bite jumping
      functional appliances.

PMID- 16420270
TI  - Facial templates: a new perspective in three dimensions.
AB  - PURPOSE: This paper describes the use of adult facial template in gender-specific
      facial analysis. SUBJECTS AND METHODS: Eighty adults, mean age 24.5, were
      selected for the study. Laser-scanned images of the subjects were obtained under
      a reproducible and controlled environment with two Minolta Vivid 900 (Osaka,
      Japan) optical laser-scanning devices assembled as a stereo-pair. A set of left
      and right scanned images was taken for each subject and each scan took an average
      of 2.5 s. These scanned images were processed and merged to form a composite
      three-dimensional soft tissue reproduction of the subjects using commercially
      available reverse modelling software. The differences in facial morphology were
      measured using shell deviation colour maps. The facial template was used to
      compare differences between males vs. females groups and two subjects with facial
      disproportions. RESULTS: The difference between the male and female facial
      templates was 1.28 +/- 1.02 mm. The areas of greatest deviation were at the
      nasal, zygomatic area and lower jaw line. The results of the surface deviation
      maps between the templates and subjects with facial disproportion showed that the
      results could be applied for orthodontic diagnosis. CONCLUSIONS: The construction
      of the adult facial templates provides an interesting perspective into measuring
      changes in groups of patients and also acts as a useful template for the
      comparison of skeletal disproportion.

PMID- 16420271
TI  - Parental craniofacial morphology in cleft lip with or without cleft palate as
      determined by cephalometry: a meta-analysis.
AB  - OBJECTIVE: To integrate findings from previous cephalometric studies comparing
      the craniofacial complex of unaffected parents with cleft lip with or without
      cleft palate (CL/P) children to controls with no history of the disease. DESIGN:
      Meta-analysis of case-control cephalometric data. INCLUSION CRITERIA: Studies
      were selected if the unaffected parents of children with CL/P were included and
      were not combined with parents of children with isolated CP; quantitative data
      were obtained through cephalometry; the cephalometric variables used were not
      unique to a study; a case-control design was used; and the means and standard
      deviations for all variables were reported or could be calculated for both the
      experimental and the control group. OUTCOME MEASURE: Using raw data obtained from
      nine studies, mean weighted effect sizes with 95% confidence intervals were
      calculated for 28 cephalometric variables (mothers and fathers combined) or 18
      variables (mothers and fathers separately). Heterogeneity statistics for the
      effect sizes were also calculated. RESULTS: In general, unaffected parents of
      children with CL/P possessed significantly wider interorbital, nasal cavity and
      upper facial dimensions, narrower cranial vaults, longer cranial bases, longer
      and more protrusive mandibles, shorter upper faces and longer lower faces
      compared with controls. Increased width of the nasal cavity was the most robust
      finding. Significant effect size heterogeneity was observed in roughly half of
      the variables examined. CONCLUSION: Unaffected parents of children with CL/P are
      characterized by a suite of consistent, yet subtle, craniofacial differences,
      which could indicate an underlying genetic liability.

PMID- 16420272
TI  - A new method for the 3D measurement of postoperative swelling following
      orthognathic surgery.
AB  - OBJECTIVE: To describe a new method for measuring facial swelling following
      orthognathic surgery using a 3D laser-scanning device. DESIGN: Prospective
      clinical trial. Setting and Sample Population -- University Dental Hospital,
      Wales College of Medicine, Biology Life and Health Sciences. Three subjects
      requiring bi-maxillary orthognathic surgery were recruited for the study.
      EXPERIMENTAL VARIABLES: Laser-scanned images of the subjects were obtained under
      a reproducible and controlled environment with two Minolta Vivid 900 (Osaka,
      Japan) optical laser-scanning devices assembled as a stereo-pair. A set of left
      and right scanned images was taken for each subject and each scan took an average
      of 2.5 s. 3D laser scans were recorded over six time periods (T1 -- pre-surgical
      scan, postoperatively: T2 -- 1 day, T3 -- 1 week, T4 -- 1 month, T5 -- 3 months
      and T6 -- 6 months). OUTCOME MEASURE: Facial scans from different time periods
      were overlaid onto the baseline (T6) facial scan to determine the reduction and
      changes in swelling following orthognathic surgery. RESULTS: The results showed
      that swelling could be accurately quantified following surgery. Furthermore,
      there was a significant reduction in the amount of swelling 1 month
      postoperatively. Furthermore, the facial morphology returned to approximately 90%
      of the baseline facial scan at 3 months. CONCLUSION: The 3D laser-scanning device
      and the method described was a reliable and accurate measure of facial swelling
      following surgery.

PMID- 16420273
TI  - Effects of low-level laser therapy on the rate of orthodontic tooth movement.
AB  - OBJECTIVES: To test the hypothesis that mechanical forces combined with low-level
      laser therapy stimulate the rate of orthodontic tooth movement. STUDY DESIGN:
      This study was a double blind, randomized placebo/control matched pairs clinical
      trial to test the efficacy of GaAlAs low-level laser therapy (LLLT) on 12 young
      adult patients who required retraction of maxillary canines into first premolar
      extraction spaces using tension coil springs with fixed edgewise appliance. LLLT
      was applied on the mucosa buccally, distally and palatally to the canine on the
      test side and using a pseudo-application on the placebo side. Dental impressions
      and casts were made at the commencement of the trial and at the end of the first,
      second and third months after starting the trial. Measurement of tooth movements
      was made on each stage model using a stereo microscope. RESULTS: There was no
      significant difference of means of the canine distal movement between the LLLT
      side and the placebo side for any time periods (p-value = 0.77). CONCLUSION: The
      energy density of LLLT (GaAlAs) at the surface level in this study (25 J/cm(2))
      was probably too low to express either stimulatory effect or inhibitory effect on
      the rate of orthodontic tooth movement.

PMID- 16420274
TI  - Alkaline phosphatase activity in gingival crevicular fluid during canine
      retraction.
AB  - OBJECTIVES: The aim of the study was to investigate alkaline phosphatase activity
      in the gingival crevicular fluid (GCF) during orthodontic tooth movement in
      humans. SETTING AND SAMPLE POPULATION: Postgraduate orthodontic clinic. Ten
      female patients requiring all first premolar extractions were selected and
      treated with standard edgewise mechanotherapy. EXPERIMENTAL VARIABLE: Canine
      retraction was done using 100 g sentalloy springs. Maxillary canine on one side
      acted as experimental site while the contralateral canine acted as control.
      OUTCOME MEASURE: Gingival crevicular fluid was collected from mesial and distal
      of canines before initiation of canine retraction (baseline), immediately after
      initiation of retraction, and on 1st, 7th, 14th and 21st day and the alkaline
      phosphatase activity was estimated. RESULTS: The results show significant (p <
      0.05) changes in alkaline phosphatase activity on the 7th, 14th and 21st day on
      both mesial and distal aspects of the compared experimental and control sides.
      The peak in enzyme activity occurred on the 14th day of initiation of retraction
      followed by a significant fall in activity especially on the mesial aspect.
      CONCLUSIONS: The study showed that alkaline phosphatase activity could be
      successfully estimated in the GCF using calorimetric estimation assay kits. The
      enzyme activity showed variation according to the amount of tooth movement.

PMID- 16420275
TI  - A case of amelogenesis imperfecta, cleft lip and palate and polycystic kidney
      disease.
AB  - OBJECTIVE: Amelogenesis imperfecta (AI) is a heterogeneous group of genetic
      disorders characterized by developmental abnormalities of tooth enamel. The AI is
      also seen as part of multi-organ abnormalities, e.g. with cone-rod dystrophy,
      hypothalamo-hypophyseal insufficiency and renal failure. The present patient with
      AI and nephrocalcinosis exhibited a phenotype different from previous cases with
      renal failure. To highlight the characteristics of this rare case, extensive
      analysis that included histological, biochemical and genetic examinations was
      performed. PATIENT: The present Japanese male patient exhibited dentition with AI
      and bilateral cleft lip and palate. Ground sections of his extracted tooth showed
      that it was hypomaturation-type AI, unlike previous cases with nephrocalcinosis
      were hypoplastic-type. He showed nephrocalcinosis and hematuria at 15 years of
      age but these symptoms appeared to be secondary to polycystic kidney disease. He
      showed skeletal Class II pattern with a retrognathic profile and retroclined
      incisors of both arches. A dolicofacial appearance was seen with an enlarged
      gonial angle. Biochemical makers including serum alkaline phosphatase,
      parathyroid hormone, calcitonin, calcium, and phosphate, were all in the normal
      range. Sequence analysis of the genes encoding amelogenin and enamelin, which are
      known to be responsible for hypoplastic-type AI, did not reveal any mutations.
      Since mouse null mutant of homeobox transcription factor, Msx2, exhibits a
      phenotype resembling AI, the human homolog of this gene, MSX2, was sequenced.
      There was a missense mutation of T447C that resulted in the conversion of
      methionine to threonine at 129.

PMID- 16420276
TI  - Influence of steroid drugs on orthodontically induced root resorption.
AB  - OBJECTIVES: To investigate the effect of acute and chronic corticosteroid
      treatment on orthodontically induced root resorption. DESIGN: 'Split mouth'
      design performing orthodontic tooth movement in 64, 6-month-old male rats divided
      into three groups: acute (n = 22), chronic (n = 23) and control group (n = 19).
      Acute and chronic group received corticosteroid treatment (8 mg/kg/day) for 3 and
      7 weeks, respectively, while no pharmacological treatment was performed in the
      control group. Performed at the Department of Orthodontics, School of Dentistry,
      University of Aarhus, Aarhus, Denmark. EXPERIMENTAL VARIABLE: The upper left
      first molar was moved mesially for 21 days in all three groups with 25 g of
      force. Undecalcified histological sections were cut at the coronal and apical
      level. OUTCOME MEASURE: The number of intersections hitting resorption lacunae
      (ES), defined as a scalloped surface with or without cementoclasts, over the
      total number of intersections hitting the root surface (RS) were recorded and
      expressed as percentage. RESULTS: The acute group showed significantly more root
      resorption at the mesio-coronal level compared with the control and the chronic
      group. CONCLUSION: This could be ascribed to the lack of balance between blastic
      activities (inhibited by the drug) and the clastic activities (enhanced or
      unchanged by drug administration) occurring in the initial phase of drug
      administration. As a consequence, a careful monitoring of patients undergoing
      acute corticosteroid treatment is suggested.

PMID- 16420277
TI  - Three-dimensional representation of the neurotransmitter systems of the human
      hypothalamus: inputs of the gonadotrophin hormone-releasing hormone neuronal
      system.
AB  - The gonadotrophin-releasing hormone (GnRH) represents the final common pathway of
      a neuronal network that integrates multiple external and internal factors to
      control fertility. Among the many inputs GnRH neurones receive, oestrogens play
      the most important role. In females, oestrogen, in addition to the negative
      feedback, also exhibits a positive feedback influence upon the activity and
      output of GnRH neurones to generate the preovulatory luteinising hormone surge
      and ovulation. Until recently, the belief has been that the GnRH neurones do not
      contain oestrogen receptors and that the action of oestrogen upon GnRH neurones
      is indirect, involving several, oestrogen-sensitive neurotransmitter and
      neuromodulator systems that trans-synaptically regulate the activity of the GnRH
      neurones. Although this concept still holds for humans, recent studies indicate
      that oestrogen receptor-beta is expressed in GnRH neurones of the rat. This
      review provides three dimensional stereoscopic images of GnRH-immunoreactive (IR)
      and some peptidergic (neuropeptide Y-, substance P-, beta-endorphin-, leu
      enkaphalin-, corticotrophin hormone-releasing- and galanin-IR) and
      catecholaminergic neurones and the communication of these potential oestrogen
      sensitive neuronal systems with GnRH neurones in the human hypothalamus. Because
      the post-mortem human tissue does not allow the electron microscopic
      identification of synapses on GnRH neurones, the data presented here are based on
      light microscopic immunocytochemical experiments using high magnification with
      oil immersion, semithin sections or confocal microscopy.

PMID- 16420278
TI  - Stroke injury in rats causes an increase in activin A gene expression which is
      unaffected by oestradiol treatment.
AB  - Activins are members of the transforming growth factor-beta superfamily that
      exert neurotrophic and neuroprotective effects on various neuronal populations.
      To determine the possible function of activin in stroke injury, we assessed which
      components of the activin signalling pathway were modulated in response to middle
      cerebral artery occlusion (MCAO). Furthermore, because oestradiol replacement
      protects against MCAO-induced cell death, we explored whether oestradiol
      replacement influences activin gene expression. Female Sprague-Dawley rats
      underwent permanent MCAO and the expression of activins and their corresponding
      receptors was determined by semiquantitative reverse transcriptase-polymerase
      chain reaction at 24 h after onset of ischaemia. We observed up-regulation of
      activin betaA and activin type I receptor A mRNA in response to injury. Dual
      label immunocytochemistry followed by confocal z-stack analysis showed that the
      activin A expressing cells comprised neurones. Next, we monitored the time course
      of activin betaA mRNA expression in oestradiol- or vehicle-treated rats at 4, 8,
      16 and 24 h after MCAO via in situ hybridisation. Starting at 4 h after injury,
      activin betaA mRNA was up-regulated in cortical and striatal areas in the
      ipsilateral hemisphere. Activin betaA mRNA levels in the cortex increased
      dramatically with time and were highest at 24 h after the insult, and oestradiol
      replacement did not influence this increase.

PMID- 16420279
TI  - Corticosterone actions on the hippocampal brain-derived neurotrophic factor
      expression are mediated by exon IV promoter.
AB  - Brain-derived neurotrophic factor (BDNF) expression is strongly regulated by
      adrenocorticosteroids via activated gluco- and mineralocorticoid receptors. Four
      separate promoters are located upstream of the BDNF noncoding exons I to IV and
      may thus be involved in adrenocorticosteroid-mediated gene regulation. In
      adrenalectomised rats, corticosterone (10 mg/kg s.c.) induces a robust down
      regulation of both BDNF mRNA and protein levels in the hippocampus peaking at 2-8
      h. To study the role of the individual promoters in the corticosterone response,
      we employed exon-specific riboprobe in situ hybridisation as well as real-time
      polymerase chain reaction (PCR) in the dentate gyrus. We found a down-regulation,
      mainly of exon IV and the protein-coding exon V, in nearby all hippocampal
      subregions, but exon II was only down-regulated in the dentate gyrus. Exon I and
      exon III transcripts were not affected by corticosterone treatment. The results
      could be confirmed with real-time PCR in the dentate gyrus. It appears as if the
      exon IV promoter is the major target for corticosterone-mediated transcriptional
      regulation of BDNF in the hippocampus.

PMID- 16420280
TI  - Acute effects of aldosterone on the autonomic nervous system and the baroreflex
      function in healthy humans.
AB  - Aldosterone has been reported to impair the baroreflex response in animal models.
      The present study aimed to investigate the acute effects of aldosterone on the
      autonomic nervous system and the baroreflex control of muscle sympathetic nerve
      activity (MSNA) and heart rate in healthy humans. Nine healthy subjects were
      examined in a double-blind, placebo-controlled, cross-over study design,
      receiving either i.v. aldosterone (100 microg) or placebo on the experimental
      day. Heart rate variability (HRV) was measured at rest, whereas blood pressure,
      heart rate and MSNA (assessed by microneurography from the peroneal nerve) were
      monitored both at rest and during baroreflex tests. Baroreceptor stimulation and
      deactivation was induced by i.v. infusion of incremental doses of phenylephrine
      and sodium nitroprusside. HRV indices at rest were specifically changed by
      aldosterone with a significant increase in standard deviation of RR intervals and
      total power, and a trend towards increased time domain parameters indicating
      parasympathetic predominance in heart rate regulation. Basal MSNA, blood pressure
      and heart rate remained unaffected by aldosterone administration. Sodium
      nitroprusside decreased diastolic blood pressure and increased MSNA as well as
      heart rate in both the aldosterone and placebo experiments. However, the
      tachycardic response to arterial baroreceptor deactivation was more pronounced in
      the aldosterone experiments. By contrast, baroreflex control of MSNA and heart
      rate during phenylephrine infusion was not affected by aldosterone. Thus, our
      study demonstrates that, in healthy humans, aldosterone tends to increase cardiac
      vagal activity and enhances the heart rate response to nitroprusside whereas MSNA
      remains unaffected.

PMID- 16420281
TI  - Evidence for a role of the GHS-R1a receptors in ghrelin inhibition of gastric
      acid secretion in the rat.
AB  - Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R) has been
      previously shown to inhibit gastric acid secretion in pylorus-ligated rats. Two
      isoforms of GHS-R have been identified: GHS-R(1a) and GHS-R(1b). The present
      study aimed: (i) to characterise the type of GHS-R involved in the central
      gastric inhibitory activity of ghrelin by using des-octanoyl ghrelin, and
      synthetic GHS-R(1a) agonist (EP1572) and antagonist (D-Lys(3)-GHRP-6) and (ii) to
      investigate the relationship between ghrelin and cortistatin (CST) in the control
      of gastric acid secretion by using the natural neuropeptide CST-14 and the
      synthetic octapeptide CST-8. The specific interactions of all the compounds with
      GHS-R(1a) were determined by comparing their ability to displace labelled ghrelin
      or somatostatin from its receptors on rat hypothalamic membranes or on rat
      cardiomyocyte, respectively. Intracerebroventricular administration of 0.01 and 1
      nmol/rat des-octanoyl ghrelin did not affect gastric acid secretion in pylorus
      ligated rats, whereas EP1572 either i.c.v. (0.01-1 nmol/rat) or i.p. (10 and 20
      nmol/kg) inhibited acid gastric secretion. Preteatment with D-Lys(3)GHRP-6 (3
      nmol/rat, i.c.v.) was able to remove the inhibitory action of ghrelin (0.01
      nmol/rat, i.c.v.) on gastric acid volume and acid output, thus indicating that
      the type 1a GHS-R likely mediates the gastric inhibitory action of ghrelin. This
      is supported by binding data showing that D-Lys(3)GHRP-6, but not des-octanoyl
      ghrelin, binds to hypothalamic GHS-R. CST-14 (1 nmol/rat, i.c.v.) did not affect
      either basal or ghrelin inhibition of gastric acid secretion. CST-8 (1 nmol/rat,
      i.c.v.) was able to counteract the gastric ghrelin response. The observation that
      CST-14 binds both GHR-S and somatostatin receptors, whereas CST-8 specifically
      displaces only ghrelin binding, indicates that CST-8 behaves as a GHS-R(1a)
      antagonist.

PMID- 16420282
TI  - Specific and time-dependent effects of glucocorticoid receptor agonist RU28362 on
      stress-induced pro-opiomelanocortin hnRNA, c-fos mRNA and zif268 mRNA in the
      pituitary.
AB  - This study examined the effects of the glucocorticoid receptor (GR) agonist
      RU28362 on stress-induced gene expression in the pituitary of rats to investigate
      mechanisms of glucocorticoid negative feedback in vivo. In an initial experiment,
      acute restraint stress produced rapid (within 15 min) induction of c-fos mRNA,
      zif268 mRNA and pro-opiomelanocortin (POMC) hnRNA within the anterior and
      intermediate/posterior pituitary as determined by quantitative real-time
      polymerase chain reaction. Treatment with RU28362 (150 microg/kg, i.p.) 60 min
      before restraint inhibited adrenocorticotrophic hormone (ACTH) and corticosterone
      secretion and selectively suppressed the stress-induced increase in POMC hnRNA in
      the anterior pituitary gland. The failure of RU28362 to surpress the stress
      induced rise in c-fos and expression of zif268 mRNA suggests that the central
      release of ACTH secretagogues was not affected at this time point by treatment
      with the GR agonist. Rather, the inhibition of ACTH release appeared to be due to
      a direct effect of RU28362 within the pituitary. A follow-up time-course study
      varied the interval (10, 60 or 180 min) between RU28362 pretreatment and the
      onset of restraint. The stress-induced increase in POMC hnRNA was completely
      blunted by RU28362 treatment within 10 min of treatment, although the stress
      induced hormone secretion, c-fos mRNA and zif268 mRNA were unaffected. The rapid
      inhibition of the stress-induced rise in POMC hnRNA in the anterior pituitary
      appears to reflect direct, GR-mediated suppression of POMC gene expression.
      RU28362 pretreatment 180 min before restraint onset was sufficient to suppress
      the stress-induced expression in the anterior pituitary gland of all three genes
      examined. Thus, the delayed negative feedback effects on hypothalamic-pituitary
      adrenal axis activity that emerged after 180 min after glucocorticoid treatment
      were not evident at 60 min. Taken together, the data suggest that the inhibition
      of the stress-induced release of ACTH apparent within the first hour of
      glucocorticoid exposure is effected at the level of the pituitary gland. The
      delayed glucocorticoid effects evident 180 min after RU28362 treatment may
      include glucocorticoid actions in the brain and additional actions within the
      pituitary.

PMID- 16420283
TI  - The suppressor of cytokine signalling 3, SOCS3, may be one critical modulator of
      seasonal body weight changes in the Siberian hamster, Phodopus sungorus.
AB  - The Siberian hamster, Phodopus sungorus, exhibits a remarkable cycle of body
      weight, reproduction and leptin sensitivity in response to a seasonal change in
      photoperiod. In the present study, we investigated the hypothesis that the
      suppressor of cytokine signalling 3 (SOCS3) plays a critical role in the
      regulation of the seasonal body weight cycle. We analysed arcuate nucleus SOCS3
      gene expression in short day length (SD; 8 : 16 h light/dark) acclimated Siberian
      hamsters that were transferred back to long day length (LD; 16 : 8 h light/dark)
      and in hamsters that spontaneously became photorefractory to SD induced by
      prolonged exposure. SD acclimated hamsters that were transferred back to LD for
      1, 2, 3, 4 or 6 weeks, increased arcuate nucleus SOCS3 gene expression to the LD
      level within 2 weeks, and maintained this higher level thereafter. The early
      increase of SOCS3 gene expression preceded the LD-induced rise in body weight by
      approximately 3 weeks. Hamsters kept in SD for an extended period (25 weeks),
      began to become refractory to SD and to increase body weight. By this time, there
      was no difference in level of SOCS3 gene expression between LD and SD
      photoperiods, although body weight was still suppressed in SD hamsters. Finally,
      we addressed whether SOCS3 gene expression is related to SD-induced gonadal
      regression or to body weight decrease by comparing Siberian hamsters with Syrian
      hamsters. The latter exhibited substantial SD-induced gonadal regression but only
      limited seasonal changes in body weight. Acclimation to either LD or SD for 14
      weeks had no effect on SOCS3 gene expression. This implies that arcuate nucleus
      SOCS3 gene expression is unlikely to be related to seasonal cycles in
      reproductive activity. Taken together, the findings further strengthen our
      hypothesis that SOCS3 may be one molecular trigger of seasonal cycles in body
      weight.

PMID- 16420286
TI  - Visceral sensation and colitis: inflammation and hypersensitivity do not always
      go hand in hand.
AB  - Visceral sensitivity and inflammation are discussed in relation to novel
      observations in the current issue of the Journal by Larsson and her colleagues.
      This paper shows that neither acute nor chronic intestinal inflammation initiated
      by dextran sodium sulfate is associated with an increase in visceral sensitivity
      to balloon distension in mice. These findings are discussed in the context of
      recent work highlighting the role of mast cells, the induction of endogenous
      antinociceptive pathways and the role of altered bacterial flora in visceral
      hypersensitivity.

PMID- 16420284
TI  - Pinealectomy reduces optic nerve but not intergeniculate leaflet input to the
      suprachiasmatic nucleus at night.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus regulates circadian rhythms
      in mammals. It receives, among others, direct inputs from the retina and from the
      thalamic intergeniculate leaflet (IGL). The former sends photic signals to the
      SCN, whereas the latter probably integrates photic and nonphotic information. To
      characterise these inputs in vivo, extracellular single-unit recordings were made
      from the SCN of rats under urethane anaesthesia during electrical stimulation of
      the optic nerve (OptN) or the IGL region. Cell responses were evaluated by
      creating peri-stimulus time histograms. Because humoral signals such as melatonin
      might modulate the activity of the SCN in addition to neural inputs, recordings
      were also made using pinealectomised (Px) rats to test for a possible role of
      this hormone in regulating inputs to the SCN. A significantly greater number of
      cells responded to IGL (60 of 90, 67%) than to OptN (35 of 75, 47%) stimulation
      in intact animals (chi(2) = 5.905, P = 0.015). The same was true when Px animals
      were tested (IGL, 82 of 131, 63%; OptN, 31 of 111, 28%; chi(2) = 27.637, P <
      0.001). In intact animals, the proportion of cells responsive to IGL stimulation
      during the day and during the night was not significantly different from the
      proportion responsive in Px animals. The same was true for OptN stimulation
      during the day. However, during the night, the proportion of cells responsive to
      OptN stimulation in intact animals was significantly greater than the proportion
      responsive in Px animals (chi(2) = 7.127, P = 0.008). Our findings suggest that a
      lack of melatonin modulates OptN but not IGL inputs to the SCN.

PMID- 16420287
TI  - Brain-gut connections in functional GI disorders: anatomic and physiologic
      relationships.
AB  - Understanding the neural regulation of gut function and sensation makes it easier
      to understand the interrelatedness of emotionality, symptom-attentive behavior or
      hypervigilance, gut function and pain. The gut and the brain are highly
      integrated and communicate in a bidirectional fashion largely through the ANS and
      HPA axis. Within the CNS, the locus of gut control is chiefly within the limbic
      system, a region of the mammalian brain responsible for both the internal and
      external homeostasis of the organism. The limbic system also plays a central role
      in emotionality, which is a nonverbal system that facilitates survival and threat
      avoidance, social interaction and learning. The generation of emotion and
      associated physiologic changes are the work of the limbic system and, from a
      neuroanatomic perspective, the 'mind-body interaction' may largely arise in this
      region. Finally, the limbic system is also involved in the 'top down' modulation
      of visceral pain transmission as well as visceral perception. A better
      understanding of the interactions of the CNS, ENS and enteric immune system will
      significantly improve our understanding of 'functional' disorders and allow for a
      more pathophysiologic definition of categories of patients currently lumped under
      the broad umbrella of FGID.

PMID- 16420288
TI  - Sensation and distribution of stress and deformation in the human oesophagus.
AB  - Evaluation of the distribution of stresses and strains in relation to distension
      induced sensation in the human oesophagus is valuable for understanding
      oesophageal biomechanics and mechano-sensation. In 12 healthy volunteers a
      specially designed oesophageal bag containing an endoscopic ultrasound probe was
      inflated to the moderate pain level. Ultrasound images, bag pressure and
      perceived sensation were recorded before and after pharmacological relaxation of
      the smooth muscle with butylscopolamine. The oesophagus was assumed to be
      circular and thick-walled. Distension induced a tensile circumferential stretch,
      radial compression and longitudinal shortening. Both circumferential strain and
      stress were highest at the mucosal surface and decreased throughout the wall. The
      stiffness increased throughout the wall and was highest at the outer surface (P <
      0.001). The decrease in stiffness in response to butylscopolamine was non
      significant. The infused volume (P = 0.012) and circumferential stress (P <
      0.001) were most closely associated with the distension-induced sensation
      (adjusted R2 = 0.88). The perceived sensation was highly individual but was
      unaffected by butylscopolamine (P > 0.08). The present study provides a method
      for computation of the stress-strain distribution throughout the wall and the
      mechano-sensory interaction in the human oesophagus. In the future, this may be
      useful for understanding of mechanoreceptor responses and generation of symptoms
      in visceral organs in health and in disease.

PMID- 16420289
TI  - Possible role of nitric oxide in visceral hypersensitivity in patients with
      irritable bowel syndrome.
AB  - BACKGROUND: Visceral hypersensitivity is a consistent finding in a considerable
      proportion of patients with irritable bowel syndrome (IBS), and may provide a
      physiological basis for the development of IBS symptoms. In this study, we aimed
      to confirm the hypothesis that nitric oxide (NO) is involved in maintaining
      visceral hypersensitivity in IBS. Ten healthy volunteers (HV) and 12 IBS patients
      with documented hypersensitivity to rectal distension underwent a rectal barostat
      study. The effect of placebo and the specific NO synthase inhibitor NG 
      monomethyl-L-arginine (L-NMMA) on resting volume, rectal sensitivity to
      distension and rectal compliance was evaluated in a double-blind, randomized,
      cross-over fashion. NG -monomethyl-L-arginine did not alter resting volumes in HV
      or IBS patients. In HV, l-NMMA did not alter rectal sensory thresholds compared
      to placebo (45 +/- 3 and 46 +/- 3 mmHg, respectively). In contrast, L-NMMA
      significantly increased the threshold for discomfort/pain in IBS patients
      (placebo: 18 +/- 2, l-NMMA: 21 +/- 3 mmHg, P < 0.05). Rectal compliance was not
      affected by L-NMMA. Although NO does not seem to play a major role in normal
      rectal sensation or tone, we provide evidence that NO may be involved in the
      pathophysiology of visceral hypersensitivity in IBS.

PMID- 16420290
TI  - A multicentre study of the management of disorders of defecation in patients with
      spina bifida.
AB  - Patients with spinal dysraphism may have severe constipation and faecal
      incontinence. The impact of antegrade colonic enema (ACE) in the management of
      patients with spina bifida (SB) is analysed. In a multicentre cross-sectional
      study, constipation, faecal incontinence and faecal management were described.
      Cases surgically treated were identified. Data were collected from 423 patients,
      of whom 230 did not use any manoeuvre or laxatives to assist evacuation.
      Conventional treatment was used in 193 patients, including digital extraction in
      39%, retrograde enema in 21% and oral laxatives in 52%. For intractable
      constipation and overflow of faecal incontinence, 47 patients were treated with
      ACE, of whom 41 used the method at a mean time of interview of 4.1 +/- 1.9 years
      after ACE operation; six abandoned ACE for conventional management. With ACE,
      faecal continence was significantly improved compared with conventional
      management, and neither retrograde rectal enema nor digital extraction were
      required. The conduit was fashioned to the right colon in 32 cases and to the
      left colon in nine cases. This study provides information on a multicentre
      experience in bowel management in SB patients. Whatever the technique used, ACE
      has improved faecal status compared with conventional therapy.

PMID- 16420291
TI  - Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an
      experimental study of conscious dogs.
AB  - Ghrelin is a peptide that was discovered in endocrine cells of the stomach.
      However, its action in regulating the fasted and fed motor activity of the
      digestive tract is not fully understood. In the present study, we examined the
      effects of an intravenous (i.v.) injection of canine ghrelin on the physiological
      fasted and fed motor activities in the stomach, duodenum, jejunum and colon of
      freely moving conscious dogs. An i.v. injection of canine ghrelin released growth
      hormone in a dose-dependent manner; however, it did not stimulate the motor
      activity of the digestive tract in either the fasted or the fed state. Moreover,
      an i.v. injection of high-dose canine ghrelin significantly reduced the motility
      index in the gastric body in the fasted state. Ghrelin did not accelerate gastric
      emptying, either. These results differ from previous reports dealing with
      rodents. It is significant that such results were obtained in research with dogs,
      which are larger animals.

PMID- 16420292
TI  - Effects and mechanisms of long-pulse gastric electrical stimulation on canine
      gastric tone and accommodation.
AB  - Gastric electrical stimulation (GES) has been applied to treat gastroparesis and
      morbid obesity. The aims of this study were to evaluate the sites of stimulation
      and the mechanisms of GES on gastric tone and accommodation. Gastric tone and
      accommodation were evaluated with a barostat in surgically prepared dogs. GES was
      applied at seven different locations, and gastric tone was assessed at each site.
      The effect of truncal vagotomy on gastric tone and accommodation and the role of
      the nitrergic pathway were also evaluated. We have found: 1) GES induced varying
      degrees of gastric relaxation at all tested locations in normal dogs; 2) Gastric
      volume was also significantly increased with GES in vagotomized dogs and the
      change tended to be lower than that of normal animals; 3) Gastric accommodation
      was reduced during GES in both the normal and vagotomized dogs and the reduction
      tended to be more in the vagotomized animals; 4) The GES-induced increase in
      gastric volume was partially abolished by intravenous nitric oxide synthase
      inhibitor. GES at various sites of the stomach exerts inhibitory effect on
      gastric tone; the most effective sites are in the antrum along the lesser or
      greater curvature; the inhibitory effect of GES on gastric tone is partially
      mediated by the vagal and nitrergic pathway.

PMID- 16420293
TI  - Effect of DSS-induced colitis on visceral sensitivity to colorectal distension in
      mice.
AB  - The present study aimed at evaluating the effect of dextran sodium sulphate (DSS)
      induced colitis on visceral sensitivity, measured as the visceromotor response
      (VMR) to colorectal distension (CRD) in BALB/c and C57Bl/6 male mice.
      Inflammation was induced by the addition of 4% DSS to the drinking water for 5
      (C57Bl/6) or 6-7 days (BALB/c). Parallel groups were used to monitor
      histopathological changes and visceral sensitivity. Pseudo-affective visceral
      pain responses were evoked using an increasing phasic CRD paradigm (10-60 mmHg)
      in conscious mice on predetermined days (pretreatment controls, 12, 16, 20, 30,
      40 and 51). In both mouse strains, significant histopathological changes
      developed between days 2 and 5 of DSS treatment, and persisted until day 12 (P <
      0.05). On day 15, inflammatory scores were reduced by about 50%. Despite evidence
      of inflammation in DSS-treated mice, no differences could be shown in the VMR to
      CRD between DSS-treated mice and controls at any time point tested. In addition,
      no differences were seen before and after DSS treatment in the same group of
      mice. In conclusion, these data suggest that DSS-induced colonic inflammation
      does not affect the visceral sensitivity to CRD, neither at short or long term,
      in BALB/c or C57Bl/6 male mice.

PMID- 16420294
TI  - Ano-rectal motility responses to pelvic, hypogastric and pudendal nerve
      stimulation in the Gottingen minipig.
AB  - We investigated the effect of efferent stimulation of the pelvic (PN),
      hypogastric (HGN) and pudendal (PuN) nerves on ano-rectal motility in Gottingen
      minipigs using an impedance planimetry probe. Changes in the rectal cross
      sectional area (CSA) at five axial positions and pressures in the rectum and anal
      canal were investigated simultaneously. Pelvic nerve stimulation elicited a CSA
      decrease in the proximal part of the rectum and a simultaneous CSA increase in
      its distal part. Anal pressure also decreased. Hypogastric nerve and PuN
      stimulation elicited an increase in anal pressure, but no rectal response.
      Severing the HGN produced a persistent reduction in resting anal pressure, but no
      change was observed when the PN and the PuN were severed. Stimulation of the
      distal part of all three nerves produced a persistent response. Administration of
      phentolamine and pancouronium eliminated the response to stimulation of the HGN
      and the PuN, respectively. CONCLUSION: Rectal responses to PN stimulation vary
      more than previously suggested. The HGN has an excitatory effect on the internal
      anal sphincter, and the PuN on the external anal sphincter. However, the PuN
      plays no major role in maintaining basal anal pressure.

PMID- 16420295
TI  - Postinfectious gastroparesis related to autonomic failure: a case report.
AB  - BACKGROUND AND AIM: Severe dysautonomia may be secondary to viral infections,
      resulting in impaired autoimmune, cardiovascular, urinary and digestive
      dysfunction. Herein, we present a case of a 31-year-old white female patient who
      had severe gastroparesis related to autonomic failure following an episode of
      acute gastroenteritis. This seems to be the first report providing thorough
      assessment of the enteric and autonomic nervous system by analysis of full
      thickness small intestinal biopsies, cardiovagal testing and autopsy. HOSPITAL
      COURSE: This patient affected by a severe gastroparesis was treated with
      antiemetics, prokinetics, analgesics and gastric electrical stimulation to
      control symptoms. Nutritional support was made using jejunal feeding tube and, in
      the final stage of disease, with total parenteral nutrition. Autonomic studies
      revealed minimal heart rate variability and a disordered Valsalva manoeuvre
      although the enteric nervous system and the smooth muscle layer showed a normal
      appearance. Hospital courses were complicated by episodes of bacteraemia and
      fungemia. Serum antiphospholipid antibodies were noted but despite
      anticoagulation, she developed a pulmonary embolism and shortly thereafter the
      patient died. Autopsy revealed acute haemorrhagic Candida pneumonia with left
      main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased
      myelinated axons with vacuolar degeneration and patchy inflammation consistent
      with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the
      stomach and small bowel revealed no evidence of enteric neuropathy or myopathy.
      CONCLUSION: A Guillain-Barre-like disease with gastroparesis following acute
      gastroenteritis is supported by physiological and autonomic studies with
      histological findings.

PMID- 16420296
TI  - Application of risk assessment and management principles to the extralabel use of
      drugs in food-producing animals.
AB  - A risk assessment of the food safety implications of drugs used in food-producing
      animals is an essential component of the regulatory approval process for products
      containing these drugs. This ensures that there is negligible risk to human
      health if these drugs are used according to the instructions that appear on the
      approved label. A relative paucity of approved products for veterinary species;
      however, forces veterinarians worldwide to use drugs in an extralabel manner to
      treat disease and alleviate suffering in animals. In food-producing animals, this
      may result in residues that are potentially harmful to the human consumer. This
      review describes how risk assessment principles can be extended to evaluate the
      risks posed by different classes of extralabel drug use. Risk management
      practices in the United States and Europe are summarized and contrasted to
      illustrate the application of these principles.

PMID- 16420297
TI  - In vitro effects of meloxicam with or without doxorubicin on canine osteosarcoma
      cells.
AB  - Cyclooxygenase (COX) inhibitors, already widely used to reduce fever,
      inflammation and pain, are under increasing consideration as potential agents for
      the prevention and treatment of neoplasia. As COX-2 was detected in human and
      canine osteosarcomas, we have evaluated the effect of the preferential COX-2
      inhibitor meloxicam on an established D-17 canine osteosarcoma cell line, which
      expressed, as well as COX-1 and COX-2 also COX-3 (as demonstrated by Western
      blot). An XTT proliferation kit was used to assess surviving cells after drug
      treatment. At low concentrations (1, 2, 4 and 10 microm) meloxicam caused an
      increase in cell numbers while a marked anti-proliferative effect was observed at
      higher concentrations (100, 200 microm) after 3 days and also 3 weeks of
      incubation. The chemotherapeutic drug doxorubicin showed a cytotoxic effect at
      all concentrations (60-1920 nm). Exposure of tumour cells to combinations of
      meloxicam and doxorubicin revealed synergistic effects (with 240 nm doxorubicin),
      as well as sub-additive and antagonistic results, especially if combined with
      concentrations of meloxicam typically found in serum. Care should be taken in
      concluding, on the basis of one in vitro study, that meloxicam does not have a
      role in the treatment of canine osteosarcomas given that the results from in vivo
      studies may differ.

PMID- 16420298
TI  - Regional differences in the in vitro penetration of hydrocortisone through equine
      skin.
AB  - Little is known about the transdermal penetration of hydrocortisone in the horse
      and, although commercial formulations containing hydrocortisone are registered
      for topical use in the horse, there have been no studies investigating the
      movement of this glucocorticoid through different regions of equine skin. Skin
      was harvested from the thorax, groin and leg (dorsal metacarpal) regions of five
      Thoroughbred geldings and frozen (-20 degrees C) until required. Defrosted skin
      was placed in Franz-type diffusion cells and the amount of radiolabelled ((3)H)
      hydrocortisone, in a saturated solution of unlabelled hydrocortisone in 50%
      ethanol (w/w), which penetrated through and remained within skin samples was
      measured over 24 h. Significantly higher (P < 0.001) maximum flux (J(max);
      mol/cm(2)/h) was measured when hydrocortisone was applied to skin from the leg,
      compared to thorax and groin, although significantly less hydrocortisone (P <
      0.001) was retained within skin from the leg at 24 h. Topical application of
      hydrocortisone in a vehicle containing ethanol would penetrate faster through leg
      skin from the lower leg when compared with the thorax or groin, which depending
      on cutaneous blood flow, may result in higher systemic drug concentrations or
      greater efficiency in treating local inflamed tissue.

PMID- 16420299
TI  - Clinical efficacy of local administration of ceftiofur in a Staphylococcus aureus
      infection in tissue cages in ponies.
AB  - Ceftiofur concentrations in an infected and uninfected environment were compared
      and the efficacy of locally administered ceftiofur was evaluated in an
      experimental infection with Staphylococcus aureus in tissue cages. Eight ponies
      had tissue cages (TCs) implanted s.c. on each side of the neck. Into one of the
      cages 150 mg of ceftiofur was administered and fluid samples were taken to
      determine ceftiofur concentrations. After 1 week the other TC was infected with
      S. aureus and subsequently treated with 150 mg ceftiofur administered locally
      into the TC once daily for 21 days. Samples of fluid were taken to determine
      ceftiofur concentrations and for bacterial counts. Ceftiofur concentrations did
      not differ significantly in the infected and uninfected environments after single
      dose of 150 mg of ceftiofur. Concentrations were considerably in excess of the
      minimum inhibitory concentration (MIC) of the S. aureus strain used. A marked
      decrease of viable bacteria in tissue cage fluid (TCF) occurred. In five of seven
      ponies; however, the infection was not eliminated and abscess formation occurred.
      Therefore, local application of ceftiofur alone is not advisable for infections
      with S. aureus in secluded sites in horses, but should be used only with
      adjunctive therapy.

PMID- 16420300
TI  - Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the
      Korean catfish (Silurus asotus).
AB  - The pharmacokinetics of florfenicol and its metabolite, florfenicol amine, was
      investigated after its intravenous (i.v.) and oral (p.o.) administration of 20
      mg/kg of body weight in Korean catfish (Silurus asotus). After i.v. florfenicol
      injection (as a bolus), the terminal half-life (t(1/2)), the volume of
      distribution at steady state (V(dss)), and total body clearance were 11.12 +/-
      1.06 h, 1.09 +/- 0.09 L/kg and 0.07 +/- 0.01 L x kg/h respectively. After p.o.
      administration of florfenicol, the t(1/2), C(max), t(max) and oral
      bioavailability (F) were 15.69 +/- 2.59 h, 9.59 +/- 0.36 microg/mL, 8 h and 92.61
      +/- 10.1% respectively. Florfenicol amine, an active metabolite of florfenicol,
      was detected in all fish. After i.v. and p.o. administration of florfenicol, the
      observed C(max) values of florfenicol amine (3.91 +/- 0.69 and 3.57 +/- 0.65
      mg/L) were reached at 0.5 and 7.33 +/- 1.15 h. The mean metabolic rate of
      florfenicol amine after i.v. and p.o. administration was 0.4 and 0.5
      respectively.

PMID- 16420301
TI  - Clomipramine and selegiline: do they influence impulse control?
AB  - Anxiety disorders in dogs are often accompanied by loss of impulse control and
      can result in inappropriate behaviour such as destructiveness, excessive barking
      and aggression. The reduction of these undesirable actions is the focus of
      behaviour therapy. Clomipramine and selegiline have been approved for the
      treatment of separation anxiety in dogs, but there are anecdotal reports that
      they produce inconsistent therapeutic effect. Hence, the aim of this study was to
      verify the efficacy of clomipramine and selegiline for regulating impulse control
      by using a rat model based on the delay of reward procedure. The principle is
      that the animal has to decide between an immediate small food reward, normally
      preferred by impulsive animals, and a delayed large food reward. In this study,
      acute effects of clomipramine (0.3-10.0 mg/kg), selegiline (0.3-3.0 mg/kg), and
      diazepam (1.0-3.0 mg/kg) on the impulsive behaviour of two breeding lines of rats
      with different anxiety-related behaviour were investigated. Neither clomipramine
      nor selegiline had an effect on impulse control in either breeding line. However,
      motor activity was decreased by clomipramine and increased by selegiline.
      Diazepam led to an increase in impulsive behaviour of one rat line concomitant
      with an increase in motor activity. The results of this rat model for studying
      impulsive behaviour suggest that a single administration of selegiline and
      clomipramine has no influence on impulsive behaviour.

PMID- 16420302
TI  - Pharmacokinetics of levamisole in broiler breeder chickens.
AB  - The pharmacokinetics of levamisole was studied in 20 broiler breeder chickens
      (chickens that give eggs to breed broilers). A single dose of levamisole (40
      mg/kg) was administered orally or intravenously to chickens before the onset of
      egg production, prelay (age = 22 weeks), and repeated at the peak of egg
      production (age = 32 weeks). A high-pressure liquid chromatographic with
      ultraviolet detection method (HPLC-UV) was used for quantification of levamisole
      in plasma. Using compartmental analysis, levamisole followed a three
      compartmental open model with mean values of alpha = 0.1224 and 0.4968, beta =
      0.01663 and 0.01813, gamma = 0.002 and 0.002/min at the prelay and at the peak of
      egg production periods, respectively. The mean values for volume of distribution
      at steady state (V(ss)), determined by compartmental analysis, were significantly
      different for prelay and peak of egg production (8.358 and 13.581 mL/kg),
      respectively.

PMID- 16420303
TI  - Pharmacological characterization of alpha1-adrenoceptors in equine digital veins.
AB  - Alpha-adrenoceptors mediate contractile responses in equine digital veins (EDVs)
      and arteries. Vascular smooth muscle alpha(1)-adrenoceptor subtypes have been
      implicated in a number of conditions, such as acute equine laminitis, and are
      therapeutic targets for the treatment of this condition. Digital veins, rather
      than arteries, were investigated in the present study because they have been
      specifically implicated in the pathophysiology of acute laminitis. The order of
      potency of a series of alpha(1)-adrenoceptor-selective agonists and antagonists
      was determined in isolated rings of EDVs under conditions of isometric tension.
      A61603 was the most potent agonist, with a higher potency (76-fold greater) than
      phenylephrine (PHE), suggesting the presence of the alpha(1A)-adrenoceptor
      subtype. Prazosin (30 nm) caused competitive inhibition of the responses to
      A61603 and PHE, with pK(b) values of 8.05 +/- 0.28 and 8.20 +/- 0.27,
      respectively. In addition, the alpha(1A)-adrenoceptor antagonist, WB4101 (10 nm),
      also caused competitive inhibition of the responses to the two agonists, with
      pK(b) values of 8.37 +/- 0.16 and 8.54 +/- 0.23, respectively, confirming the
      presence of the alpha(1A)-adrenoceptor subtype in EDVs. The selective alpha(1D)
      adrenoceptor antagonist, BMY7378 (100 nm) did not cause a significant change in
      the response to the agonists, giving lower pK(b) values (6.97 +/- 0.27 and 6.88
      +/- 0.17 vs. A61603 and PHE, respectively). Chloroethylclonidine dihydrochloride
      (45 microm, 30 min), used to produce selective inactivation of alpha(1B)
      adrenoceptors, caused noncompetitive inhibition of the response to PHE, but was
      without effect on the response to A61603. These findings indicate that EDVs
      possess at least two different alpha(1)-adrenoceptor populations, which are
      predominantly of the alpha(1A) and alpha(1B) subtypes. These data may assist in
      the development of more selective antagonists for therapeutic use in horses.

PMID- 16420304
TI  - Comparative pharmacokinetics of medetomidine enantiomers in goats and sheep
      during sevoflurane anaesthesia.

PMID- 16420305
TI  - Lack of effect of diet on the pharmacokinetics of enrofloxacin in horses.

PMID- 16420307
TI  - CD10 expression in trichoepithelioma and basal cell carcinoma.
AB  - BACKGROUND: Trichoepithelioma (TE) is a benign neoplasm that shares both clinical
      and histologic features with basal cell carcinoma (BCC). However, it is important
      to distinguish these neoplasms. Limited immunohistochemical stains are available
      to separate these two tumors. METHODS: CD10 protein immunohistochemistry was
      performed on paraffin-embedded biopsies of 13 TE and 23 BCC diagnosed by routine
      microscopy. Cases were analyzed for pattern of CD10 expression by tumor cells and
      surrounding stroma. RESULTS: Twelve of 13 (92%) TE showed positive stromal
      immunoreactivity. Of these, eight cases also demonstrated positivity of the
      papilla, and two also showed positivity of the basaloid cells. No TE demonstrated
      epithelial expression alone. On the other hand, expression of CD10 by basaloid
      cells was identified in 20 (87%) cases of BCC. Stromal positivity was also
      identified in three cases of BCC. Condensation of CD10-positive stromal cells
      around basaloid nests was statistically significant in differentiating TE from
      BCC (p < 0.0001). Conversely, CD10-positive basaloid cells were seen
      predominantly in BCC (p < 0.0001). CONCLUSIONS: This study demonstrates a
      statistically significant difference in CD10 staining pattern between TE and BCC.
      Thus, CD10 may be a useful adjunct marker in distinguishing these tumors.

PMID- 16420308
TI  - Defective beta1-integrins expression in arsenical keratosis and arsenic-treated
      cultured human keratinocytes.
AB  - BACKGROUND: beta1-integrins, which localize to the basolateral surface of basal
      keratinocytes, are important in the differentiation control and proliferation of
      the epidermis. Many cutaneous diseases with perturbed differentiation, including
      arsenical keratosis, show altered patterns of integrin distribution and
      expression. Arsenic may induce arsenical keratosis through the differentiation
      and apoptosis aberration by integrins. The purpose of this study is to
      investigate the role of integrin and arsenic in the pathogenesis of arsenical
      keratosis. METHODS: Twenty-five specimens obtained from 25 patients with
      arsenical keratosis disease were studied. Immunohistochemistry staining to beta1,
      alpha2beta1, or alpha3beta1 integrins was performed in arsenical keratosis and
      clinically normal perilesional skin. Western blotting was used to assess the
      expression of integrin beta1 and focal adhesion kinase (FAK) in arsenic-treated
      cultured keratinocytes. RESULTS: A decreased expression of beta1, alpha2beta1, or
      alpha3beta1 integrins was demonstrated in arsenical keratosis and clinical normal
      perilesional skin in a large proportion of arsenical keratosis cases studied. The
      expressions of integrin beta1 and FAK were both decreased in arsenic-treated
      keratinocytes. CONCLUSIONS: Our results suggest that arsenic induces abnormal
      differentiation in arsenical keratosis via the effects of integrin expression in
      keratinocytes.

PMID- 16420309
TI  - Implication of MT1-MMP in the maturation steps of benign melanocytic nevi.
AB  - BACKGROUND: Metalloproteinases (MMPs) are proteins involved in extracellular
      matrix breakdown and have been implicated in stages of migration and metastasis.
      MT1-MMP is an MMP anchored to the cell membrane. During maturation, melanocytic
      nevi penetrate the extracellular matrix and express MMPs. METHODS: We studied 10
      junctional, 10 compound, and 10 intradermal nevi diagnosed by clinical and
      histological studies and by performing immunohistochemical study to assess MT1
      MMP activity. RESULTS: We found evidence of MT1-MMP expression in melanocytic
      nevus cells, particularly around the entire border of cell nests. Expression was
      more intense in junctional nevi and gradually decreased with acquisition of
      intradermal component and became nonexistent in nevi in the deep dermis.
      CONCLUSIONS: MT1-MMP is expressed in the membrane of nevus cells, with expression
      greater in nest cells in contact with the extracellular matrix. The intensity of
      expression correlated inversely with the maturation phase of the nevus, being
      very high in junctional nevi and low in intradermal nevi.

PMID- 16420310
TI  - Expression of stromal cell markers in distinct compartments of human skin
      cancers.
AB  - BACKGROUND: The importance of changes in the supporting tumor stroma for cancer
      initiation and progression is well established. The characteristics of an
      activated tumor stroma, however, are not completely understood. In an effort to
      better characterize the desmoplastic response to human skin tumors, we evaluated
      the expression pattern of three stromal cell markers, fibroblast-activation
      protein (FAP), endoglyx-1, and endosialin, in a series of melanocytic and
      epithelial skin tumors. METHODS: Immunohistochemistry using antibodies against
      FAP, endoglyx-1, and endosialin was carried out in skin samples obtained from 43
      patients. Furthermore, microarray data from an independent set of human skin
      cancers were analyzed. RESULTS: FAP-positive fibroblasts were detected in all
      tumor tissues tested, including cases of melanocytic nevi, melanoma metastases,
      basal cell carcinomas, and squamous cell carcinomas. In cutaneous melanoma
      metastases, we identified different compartments within the stromal response on
      the basis of the regions of FAP expression. Endoglyx-1 expression was confined to
      normal and tumor blood vessel endothelium including 'hot spots' of
      neoangiogenesis within the cutaneous melanoma metastases. Endosialin was
      selectively induced in subsets of small- and medium-sized tumor blood vessels in
      melanoma metastases and squamous cell carcinomas. CONCLUSIONS: These data
      describe novel aspects of stromal marker expression in distinct compartments of
      human skin tumors and may point to potential targets for novel therapeutic
      strategies aimed at the tumor stroma.

PMID- 16420311
TI  - International Board Certification in Dermatopathology: a worldwide effort to
      raise standards in dermatopathology.

PMID- 16420312
TI  - Core competencies in dermatopathology.
AB  - Medical education has traditionally focused on imparting medical knowledge,
      delivering quality patient care, and teaching research methodology. Various
      measures of success, including standardized testing, have been developed to
      assess the achievement of those goals. These measures then served as
      documentation of the effectiveness of individual training programs. However, in
      1999, the Accreditation Council for Graduate Medical Education (ACGME) changed
      the way we measure the success of medical education. They developed six core
      competencies for medical education and assigned the task of enforcing them to the
      individual Residency Review Committees. By July 2006, all accredited programs,
      including dermatopathology fellowships, must use measurable, competency-based
      objectives, and assess achievement of those objectives. Programs should also be
      documenting ways they are improving the evaluation process. They must be in full
      compliance with implementation, measurement, and assessment of the six core
      competencies for accreditation. The next phase required by the ACGME involves
      developing curriculum based on competencies as well as using resident, fellow, or
      graduate competency performance to assess success in preparing trainees for the
      practice of medicine. This manuscript discusses measurable objectives to address
      the core competencies for dermatopathology fellowship training as well as
      dermatopathology rotations in dermatology and pathology residency training.

PMID- 16420313
TI  - Two sporadic cases of adult-onset progressive mucinous histiocytosis.
AB  - Progressive mucinous histiocytosis is a rare, benign, non-Langerhans' cell
      histiocytosis limited to the skin. Ten cases--all women--in four families and one
      sporadic case have been described in the literature. The disorder usually begins
      in childhood and progresses slowly. We report two sporadic cases of adult-onset
      progressive mucinous histiocytosis in unrelated African-American women, aged 48
      and 55 years, respectively, who developed red-brown and flesh-coloured,
      asymptomatic papules on the face, the arms and the legs without truncal, mucosal
      or visceral involvement. The lesions showed no spontaneous regression. Both
      patients lacked associated systemic symptoms, including polyuria, polydipsia or
      seizures. There was no underlying hyperlipidaemia, paraproteinaemia or
      lymphoproliferative disease. No family history of similar lesions could be
      identified. Light microscopy revealed dermal proliferation of spindle-shaped
      histiocytes with abundant mucin deposition. Electron microscopy demonstrated a
      high number of myelin figures or zebra bodies in the cytoplasm of histiocytes. On
      immunohistochemistry, positive staining with macrophage markers--CD68, HAM56 and
      lysozyme--and factor XIIIa, a transglutaminase present in dermal dendrocytes, and
      negative staining with Langerhans' cell markers--CD1a and S100--and CD34, a
      marker present in dermal dendritic cells derived from uncommitted mesenchymal
      cells, were observed.

PMID- 16420315
TI  - Intraoral lesions associated with sebaceous nevus syndrome.
AB  - The sebaceous nevus syndrome describes the rare association of a sebaceous nevus
      with systemic features such as mental retardation, seizures and colobomas (among
      others). It is thought to be a cutaneous mosaic inherited as a paradominant
      trait. Three cases are provided illustrating the intraoral manifestations of the
      syndrome. The first histological comparison of contiguous mucosal and cutaneous
      lesions is provided. We also describe the possible association of SFM syndrome
      with a benign fibrous histiocytic lesion of the mandible. This and other
      mandibular tumors associated with the sebaceous nevus syndrome may have
      significant implications for patients. Awareness of the potential presence or
      development of significant intraoral lesions in association with the sebaceous
      nevus syndrome is important for those involved in the care of patients with this
      syndrome.

PMID- 16420314
TI  - Langerhans cell histiocytosis associated with myelodysplastic syndrome in adults.
AB  - BACKGROUND: Myelodysplastic syndrome (MDS) is a group of bone marrow disorders
      associated with dyplasia of myeloid elements that may have cutaneous
      manifestations including infections, vasculitis, Sweet's syndrome, pyoderma
      gangrenosum, erythema elevatum diutinum, and leukemia cutis. These cutaneous
      manifestations are attributed to the underlying bone marrow defect. Langerhans
      cell histiocytosis (LCH) is primarily a pediatric disease, and rarely LCH has
      been described in association with pediatric MDS. We are aware of only a single
      case report of LCH associated with MDS in an adult. METHODS: We report two new
      cases of LCH in elderly patients with underlying MDS. The specimens were examined
      by routine microscopy as well as immunohistochemical stains for S100 protein and
      CD1a. RESULTS: Both patients were elderly men with established diagnoses of MDS.
      One presented with a solitary pruritic papule while the other had a 2-year
      history of erythematous papules involving the trunk and extremities. Histologic
      examination revealed intraepidermal and dermal collections of mononuclear cells
      with reniform nuclei. The cells were strongly positive for S100 and CD1a,
      confirming their identity as Langerhans cells. CONCLUSION: Cutaneous LCH may be
      associated with underlying MDS in adults and should be considered in the
      differential diagnosis of cutaneous eruptions in patients with MDS.

PMID- 16420316
TI  - Cutaneous metastases from adenocarcinoma of the rete testis.
AB  - Adenocarcinoma of the rete testis (ACRT) is extremely rare and has only been the
      subject of sporadic case reports, in most of which the neoplasm manifested as a
      scrotal mass with diffuse enlargement of the testis. Only a few cases of scrotal
      infiltration by a contiguous ACRT have been described. To our knowledge, none
      have reported distant skin metastases. We report a case of ACRT presenting with
      suprapubic skin metastases. The diagnosis was based on clinical and
      histopathological findings and supported by the results of immunohistochemical
      and ultrastructural studies. We discuss the differential diagnosis to this rare
      entity, which include metastatic adenocarcinoma, serous tumor of the testis, and
      mesothelioma of the tunica vaginalis.

PMID- 16420318
TI  - HMB-45 expression in a clear cell variant of atypical fibroxanthoma.

PMID- 16420319
TI  - Reproductive and endocrine characteristics of delayed pubertal ewe-lambs after
      melatonin and L-tyrosine administration.
AB  - The investigation was carried out to study the impact of melatonin and L-tyrosine
      administration on the onset of cyclicity in delayed pubertal ewe-lambs. Fifteen
      delayed pubertal ewe-lambs (age >16 months) were used in this study after being
      assigned randomly into three groups. In the first group (melatonin treated group,
      n = 5), each lamb was administered 3 mg melatonin orally at 16:00 hours from 1
      July to 15 September while in the second group (L-tyrosine treated group, n = 5),
      each lamb was administered L-tyrosine at the level of 100 mg/kg b.w. as a single
      oral dose. The third group (n = 4) served as control. Lambs were exposed to
      mature, fertile rams daily and blood samples were collected twice weekly. The
      progesterone concentrations (P4 evaluations) were significantly higher (p < 0.05)
      in treated groups than the control group. Ovarian activity, assessed by P4
      evaluations, showed that all animals in the first group came in oestrus and from
      them four got pregnant (80%) while in the second group, only three lambs came in
      heat and from them two became pregnant (40%). On the contrary, none of the
      control lambs showed oestrus. In conclusion, this study confirmed that the oral
      administration of melatonin and L-tyrosine played an essentially physiological
      roles to induce cyclicity in delayed pubertal ewe-lambs and improved their
      reproduction.

PMID- 16420321
TI  - Bacteriological findings and hormonal profiles in the postpartum Balady goats.
AB  - Twenty-six Balady goats categorized according to parity into primiparous and
      pluriparous goats were used to investigate bacterial flora of the genital tract
      and hormonal profiles during the postpartum (PP) period. Escherichia coli and
      Staphylococcus aureus were isolated in pure or mixed culture from the uterus.
      Arcanobacterium pyogenes was isolated from swabs obtained from the vagina and
      cervix of one primiparous goat. Uteri and cervices but not vaginas were free of
      bacterial contamination by day 10 PP except for one pluriparous goat with scanty
      E. coli contamination on day 25 PP. Fluctuating oestradiol 17beta (E2) levels
      demonstrated resumption of follicular activity as early as day 13 PP in both
      parity groups. Progesterone (P4) levels remained low at basal levels throughout
      the study period. Higher concentrations of 15-keto-13,14-dihydroprostaglandin
      F2alpha (PGFM) were observed during the first week PP compared with the rest of
      the PP period. PGFM concentrations dropped to low basal level by day 10 PP and
      remained constantly low throughout the study period. P4, E2 and PGFM profiles
      were not different between the different parity groups. In conclusion,
      intrauterine infection is not common in goats with normal kidding. E. coli was
      the most common intrauterine bacterial isolate. E2 and P4 profiles were
      consistent with resumption of follicular growth but not ovulation. High PGFM
      concentrations coincided with the fast regression phase of uterine involution.
      Hormonal profile and bacterial contamination and clearance were similar to those
      reported in other related species and not related to parity.

PMID- 16420320
TI  - Mitochondrial activity, distribution and segregation in bovine oocytes and in
      embryos produced in vitro.
AB  - Contents Bovine oocytes and embryos produced in vitro were studied to determine
      the mitochondrial pattern of distribution, segregation and activity using DIOC 6
      and Jc-1 fluorescence. The highest fluorescence level observed in mature oocytes
      was taken as 100% activity and six activity levels were estimated as follows: (1)
      0%, (2) 1-15%, (3) 16-30%, (4) 31-50%, (5) 51-75% and (6) 76-100%. Three patterns
      of mitochondrial distribution were found: (1) diffused throughout the cytoplasm
      in oocytes and embryos, (2) pericytoplasmic in oocytes and embryos, and (3)
      perinuclear only in embryos. The segregation of mitochondria in blastomeres
      showed two distinct patterns: (1) symmetrical with an even mitochondrial
      population, and (2) asymmetrical with different numbers of mitochondria in each
      blastomere. In immature oocytes, mitochondrial activity was very low and the
      distribution was diffuse or negligible, while in mature oocytes the activity was
      high and the distribution was diffuse or pericytoplasmic. Competent embryos up to
      the 16-cell stage showed intermediate levels of activity (16-50%) but activity
      decreased thereafter up to the blastocyst stage. Non-competent embryos showed low
      levels of activity (1-15%) at all stages. These results suggest that mitochondria
      might play an important role during early development and that a minimum
      threshold of activity regulates the potential competence for reaching the
      blastocyst stage.

PMID- 16420322
TI  - Meiotic competence of canine oocytes embedded in collagen gel.
AB  - The present study was conducted to examine the meiotic competence of canine
      oocytes embedded in collagen gel, and to investigate the effects of timed
      exposure of the oocytes embedded in collagen gel to gonadotrophins during
      maturation culture, on their nuclear maturation. Cumulus-oocyte complexes (COCs)
      were collected from bitches at the anoestrous and dioestrous stages of the
      reproductive cycle. In the first experiment, half of the COCs were embedded in
      collagen gels. The COCs with or without collagen-gel embedding were cultured in a
      TCM-199 medium supplemented with 0.1 IU/ml human menopausal gonadotropin (hMG)
      and 10 IU/ml human chorionic gonadotropin (hCG) for 72 h. In the second
      experiment, the COCs embedded in collagen gels were cultured in TCM-199 medium
      with gonadotrophins (hMG and hCG) for various periods (0, 24, 48 and 72 h) and
      then cultured in the medium without gonadotrophins until reaching total culture
      period (72 h). The percentage of the oocytes reaching metaphase I and metaphase
      II (MI/MII) was significantly higher (p < 0.05) in COCs with collagen-gel
      embedding than in COCs without collagen-gel embedding. The percentage of oocytes
      that were arrested at the germinal vesicle stage was significantly lower (p <
      0.05) in oocytes cultured with gonadotrophins than in oocytes cultured without
      gonadotrophins. However, there were no significant differences in the percentages
      of oocytes that reached each stage of meiosis among the groups, irrespective of
      the duration of exposure to gonadotrophins. These observations indicate that
      embedding of COCs by collagen gel enhances the meiotic competence of canine
      oocytes, but removal of hormone supplement from maturation medium does not
      improve the ability of the oocytes to reach MII stage.

PMID- 16420323
TI  - True hermaphroditism in six female littermates after administration of synthetic
      androgens to a pregnant bitch.
AB  - A pregnant bitch was treated with a synthetic testosterone mixture on
      approximately day 40. The female offspring (six pups) showed an increased
      anogenital distance, vaginal enlargement and a variable amount of vaginal
      discharge. The urinary orifice was found dorsally in the vestibulum, stooled on a
      protruding phallus-like structure. All six pups underwent a laparotomy and
      subsequent spaying and a modified ventral episioplasty technique to lift up the
      labia to a more vertical position in order to prevent urine accumulation.
      Histopathological examination of the genital tracts demonstrated the presence of
      bilateral ovotestis and remnants of the Wolffian duct system in all cases. The
      finding of true hermaphroditism of the offspring after exogenous androgen
      administration during gestation of the bitch has not yet been reported elsewhere.

PMID- 16420324
TI  - The prediction of parturition date in canine pregnancy.
AB  - In bitches, the length of gestation is highly variable when measured from the day
      of mating, thus prediction of parturition may be greatly inaccurate when
      determined from this point. The ability to precisely predict the duration of
      pregnancy is of practical importance for managing parturition or planning
      caesarean section and this review analyses the methods that can be used to
      accurately forecast the day of parturition. At the time of breeding,
      determination of the luteinizing hormone surge and the initial rise in
      progesterone provide reliable information on gestational length of the bitch, but
      when pregnancy is ascertained, ultrasonography is the most useful tool to predict
      the delivery day. In fact, by ultrasonographic measurements of the extra-foetal
      and foetal structures an accurate prediction can be made both in early and late
      pregnancy.

PMID- 16420325
TI  - Motility and plasma membrane integrity of spermatozoa in fractionated stallion
      ejaculates after storage.
AB  - With the aim of investigating properties of stallion seminal plasma to eventually
      improve semen-handling techniques, sperm motility and plasma membrane integrity
      were analysed in different fractions of the ejaculates after storage. Semen was
      collected using a computer-controlled automated phantom that separates the
      ejaculates into five successive cups. Samples containing seminal plasma and skim
      milk extender were compared with samples stored in skim milk extender after the
      removal of seminal plasma by centrifugation. Fractionated ejaculates were stored
      cooled for 24 h after dilution with extender (Expt 1) or frozen in liquid
      nitrogen (Expt 2). In Expt 1, cup 1 was pre-sperm fluid, cups 2 and 3 sperm-rich
      fractions, and cup 4 sperm-poor fractions. In Expt 2, cups 1 and 2 were sperm
      rich fractions, and cups 3 and 4 sperm-poor fractions. One sample (WE)
      represented the whole ejaculate in both experiments. Motility parameters were
      determined with a Hamilton-Thorn Motility Analyzer, and plasma membrane integrity
      was assessed using carboxyfluorescein diacetate and propidium iodide staining and
      fluorescence microscopy. The removal of seminal plasma lowered motility values,
      but not plasma membrane integrity, in both experiments. No significant
      differences between cups were observed after cooled storage. The cups differed
      significantly in most post-thaw motility parameters, and the sperm-rich fraction
      showed higher post-thaw motility than the whole ejaculate.

PMID- 16420327
TI  - Incidence of unilateral fertilizations after low dose deep intrauterine
      insemination in spontaneously ovulating sows under field conditions.
AB  - A new procedure for non-surgical deep intrauterine insemination (DUI) in
      unrestrained sows hormonally induced to ovulate, has been reported. In comparison
      with standard artificial insemination (AI), with this procedure, the sperm
      numbers inseminated can be reduced 20-fold without reducing the reproductive
      performance of these hormonally treated sows. The present study evaluated, using
      two experiments, the reproductive performance applying 20-fold different sperm
      numbers per AI dose using DUI or standard AI in spontaneously ovulating sows,
      under field conditions. In experiment 1, AI was applied to crossbred sows at 12,
      24 and 36 h after onset of spontaneous oestrus using one of the following two
      regimes: (i) DUI (treatment) with 0.15 x 10(9) fresh boar spermatozoa in 5 ml of
      Beltsville thawing solution (BTS) extender (n = 95), and (ii) standard cervical
      AI (control) with 2.85 x 10(9) fresh spermatozoa in 95 ml of BTS extender (n =
      95). The farrowing rates of the two groups of sows were statistically similar
      (NS). However, a decrease (p < 0.002) in litter size and the total number of pigs
      born alive was observed in sows inseminated with the DUI procedure. In experiment
      2, 42 post-weaned oestrus sows were inseminated following the same design
      described for experiment 1 during spontaneous oestrus. On day 6 after onset of
      oestrus, the proximal segment of the uterine horns of the sows were flushed under
      surgery to retrieve eventual embryos and evaluate the success of fertilization
      per cornua (e.g. occurrence of effective uni- vs bilateral sperm transport
      rendering uni- or bilateral, complete or partial fertilization). Retrieved
      embryos were assessed for cleavage and number of accessory spermatozoa. Although
      identical overall pregnancy rates were achieved in both insemination groups, the
      percentage of sows with partial bilateral fertilization and unilateral
      fertilization was markedly higher (p < 0.05) in the DUI group (35%) compared with
      the control (standard AI) group (5%), with a consequent lower (p < 0.001)
      percentage of viable early embryos after DUI. The number of accessory spermatozoa
      in the zona pellucida of the embryos was highly variable, but higher (p < 0.001)
      in control animals than in DUI-AI. No accessory spermatozoa were found in oocytes
      retrieved from sows depicting unilateral fertilization. In conclusion, DUI in
      spontaneously ovulating sows with 0.15 x 10(9) spermatozoa renders similar
      farrowing rates but a lower litter size compared with use of standard AI with a
      20-fold higher sperm dose. The lower litter size ought to be related to a
      decreased distribution of spermatozoa after DUI leading to a higher incidence of
      partial bilateral and unilateral fertilization.

PMID- 16420326
TI  - Effects of beta-OH butyrate on bovine granulosa and theca cell function in vitro.
AB  - In this study, the effects of beta-OH butyrate (BHB) levels, associated with a
      negative energy balance, on bovine granulosa and theca cell function were
      investigated in vitro. Granulosa and theca cells of healthy large follicles (>8
      mm), obtained from slaughterhouse ovaries, were cultured in serum free medium
      containing 0, 0.5, 1 or 1.5 mm BHB and 3 mm glucose, to mimic the situation in
      the early postpartum dairy cow. Hormone concentrations (progesterone, oestradiol
      17beta and/or androstenedione) in spent medium and cell numbers were measured
      after 48 h of culture. No effects of BHB on theca cell numbers or on steroid
      production were observed. In granulosa cells, all BHB treatments evenly increased
      cell numbers (p < 0.05), while they reduced progesterone and oestradiol-17beta
      production per cell (p < 0.05). These effects may be attributed to the use of BHB
      as energy source which is however differently metabolized than glucose.
      Conclusively, in the presence of physiological glucose concentrations BHB can
      modulate granulosa but not theca cell function in vitro.

PMID- 16420328
TI  - A screening for the occurrence of autoreactive antibodies in sera of pregnant and
      non-pregnant bitches.
AB  - Sera of healthy pregnant (group I, n = 11) and non-pregnant (group II, n = 11)
      bitches were screened for autoantibodies (AAb). In both groups, blood samples
      were drawn every fifth day between days 5 and 55 after mating. Serum was analysed
      via indirect immunofluorescence (IIF) with the Canine ANA HEp-2 Screening Kit. In
      all animals, anticytoplasmic AAb were detected. Utilizing primate-heart substrate
      slides AAb against contractile proteins of the cytoplasm could be observed. The
      predominating fluorescence pattern in pregnant animals resembled above all
      desmin, which was proven via Western blot. The sera were then pre-incubated with
      tropomyosin, actin, vimentin, vinculin and keratin solutions, and assessed on HEp
      2 slides and on human and canine fibroblasts as well. The latter substrate was
      used to verify whether the detected Ab were in fact AAb. Utilizing tropomyosin,
      revealed elimination of the cytoplasmic fluorescences on all three substrates. It
      is therefore assumed, that in sera of healthy dogs, AAb against contractile
      structure proteins of the cytoplasm are present regularly. The majority of
      pregnant bitches presented with higher end-point titres (EPT), than to be found
      in non-pregnant dogs. AAb against desmin played the key role in those patterns.
      In addition, sera were screened for thyroid specific AAb, namely thyroglobulin,
      thyroid peroxidase (TPO), T3 and T4, and for AAb against insulin by ELISA or
      Western blot (TPO). Only in two of the pregnant bitches a weak positive reaction
      (1:100) for T3-AAb was detected.

PMID- 16420330
TI  - Normal values for the scrotal circumference in rams of gotlandic breed.
AB  - Selection of fertile sires is crucial for profitable lamb production. Males with
      larger testes tend to sire daughters that reach puberty at an earlier age and
      ovulate more ova during each oestrus period. Measurement of the scrotal
      circumference (SC) is thus an essential part of the breeding soundness
      evaluation. Testicular size varies with breed, age and time of the year. No SC
      values or recommendations for minimal values have been established in any of the
      Scandinavian domestic sheep breeds. Data were recorded of the SC, age and weight
      in 245 ram lambs and 27 mature rams of the Gotlandic breed, which is the breed
      that constitutes about 50% of the Swedish sheep population. For the ram lambs,
      the overall mean SC was 28.9 (+/-1.9) cm at an average age of 170 (+/-9) days and
      mean weight of 53.5 (+/-7.0) kg, and the mean SC varied between 27.1 and 29.6 cm
      depending on age and weight. For mature rams (17-54 month old), the mean SC was
      32.4(+/-2) cm. To provide a practical tool for exclusion of rams with sub-optimal
      reproductive capacity (abnormal testes or those with small testes because of
      delayed puberty) a threshold value was established based on the average SC minus
      2 SD. The calculated minimal SC is 26 cm for ram lambs >5.5 months of age with a
      body weight of >50 kg. For mature rams, minimum SC is 28 cm regardless of weight
      and age.

PMID- 16420329
TI  - Influence of seasons, extenders, slow and rapid freezing on seminal characters in
      Korean native bucks.
AB  - The success of AI technology is based on both semen quality and freezing process.
      In order to establish the semen freezing techniques in Korean native bucks,
      factors affecting the success were evaluated in the present study. Semen
      collected by electro-ejaculation from bucks during four distinct seasons was
      evaluated for semen volume and pH, sperm motility and survivability. The semen
      volume, concentration and total cell were higher in spring, summer and less in
      winter. Yet, there were no seasonal differences in the proportional data of live
      sperm, motility score and pH of semen among seasons. The percentage of live sperm
      after thawing was found to increase with increased concentration of lactose in
      Tris-Egg yolk-glycerol (TY-G), being highest in TY-G supplemented with 180 mm
      lactose (TYL180-G), but did not differ between TY-G and TYL120-G. Sperm motility
      was enhanced by employing 2.0 h equilibration time with rapid freezing method. In
      conclusion, semen could be frozen with high success rates for further use of AI
      in breeding techniques and to preserve the Korean native bucks.

PMID- 16420331
TI  - Update on semen technologies for animal breeding.
AB  - Despite the scale of the livestock breeding industry, where many millions of
      insemination doses are prepared each year, sperm preparation techniques are used
      infrequently in animal assisted reproduction compared with its human counterpart.
      However, some of the techniques used for human sperm preparation, for example,
      density gradient centrifugation, improve the quality of sperm preparations which
      is, in turn, reflected by an increased conception rate. The preparation technique
      separates motile spermatozoa with normal morphology and intact DNA from the total
      sperm population, leaving behind immature or senescent spermatozoa,
      morphologically abnormal ones and those with damaged DNA. Furthermore, the motile
      spermatozoa are removed from the seminal plasma which carries cells, cellular
      debris and reactive oxygen species, as well as pathogens. Gradient-prepared
      spermatozoa survive longer, either in liquid storage or when cryopreserved, and
      are free of bacteria and viral infectivity if prepared carefully. Preparation
      techniques such as density gradient centrifugation, or the simplified single
      layer centrifugation technique, have considerable potential for aiding sperm
      preparation from poor quality semen samples, such as may be obtained from
      unselected semen donors in captive breeding programmes, or from performance
      horses. Moreover, the removal of pathogens has important implications, both for
      disease control and for avoiding the use of antibiotics in semen extenders, which
      can be detrimental to sperm survival.

PMID- 16420333
TI  - Influence of temperature during glycerol addition and post-thaw dilution on the
      quality of canine frozen semen.
AB  - Contents The aim of the present study was to compare the influence of room
      temperature (27 degrees C) and 4 degrees C during glycerol addition on canine
      semen cryopreservation and verify the effect of different post-thawing dilutions
      on canine semen. Ten ejaculates from five stud dogs were collected by digital
      manipulation. Semen samples were evaluated and further divided into two aliquots.
      The first aliquot was extended in Tris-egg yolk-glycerol at 27 degrees C and the
      second one received glycerol at 4 degrees C. Samples were frozen and stored in
      liquid nitrogen. After 1 week, samples were thawed and submitted to evaluations
      of progressive sperm motility, morphology, acrosomal integrity, hypo-osmotic
      swelling (HOST) and thermoresistance tests. For thermoresistance test, aliquots
      were divided in two portions: one portion was kept undiluted (1 : 0) and the
      other one was diluted in a 1 : 4 ratio (one part semen to four parts extender).
      No differences were observed between temperatures for glycerol addition regarding
      seminal parameters evaluated. Furthermore, post-thawing dilutions demonstrated
      similar effect on canine semen longevity. Correlations among post-thaw sperm
      motility and HOST and results from thermoresistance test were observed for both
      temperatures for glycerol addition. In conclusion, glycerol could be added to
      canine semen at room temperature (27 degrees C) or at 4 degrees C. Moreover,
      there is no need to extend canine semen after thawing for the thermoresistance
      test, but if we need to increase the inseminating volume for artificial
      inseminations, the addition of extender will not damage the semen.

PMID- 16420332
TI  - Studies on the effect of supplementing boar semen cryopreservation media with
      different avian egg yolk types on in vitro post-thaw sperm quality.
AB  - Fertility after insemination of cryopreserved boar semen is currently below that
      of fresh semen. In an attempt to improve the post-thaw motility and acrosome
      integrity of boar sperm, semen was frozen using an adapted Westendorf method in
      which the chicken egg yolk was replaced by either duck or quail egg yolk. The
      different composition of the yolk types, particularly the amount of cholesterol,
      fatty acids and phospholipids, were thought to potentially afford a greater level
      of protection to sperm against damage during freezing and thawing. Sperm frozen
      in medium containing chicken egg yolk displayed higher motility immediately after
      thawing, but there was no difference in the motility of sperm frozen with
      different types of egg yolk 3 or 6 h after thawing and maintenance at 37 degrees
      C. Sperm frozen in media containing chicken or duck egg yolk had a higher
      proportion of intact acrosomes immediately after thawing than sperm frozen in
      medium containing quail egg yolk, but 6 h after thawing and maintenance at 37
      degrees C the sperm that had been frozen in medium containing chicken egg yolk
      had a higher proportion of intact acrosomes than the sperm frozen in media
      containing duck or quail egg yolk. Analysis of the composition of the different
      yolk types showed that the basic components of the yolks were similar, but the
      ratios of fatty acids and phospholipid classes differed. Duck egg yolk had more
      monounsaturated fatty acids (MUFA) than chicken egg yolk, which had more MUFA
      than quail egg yolk. Duck egg yolk contained more phosphotidylinositol (PI) than
      chicken or quail egg yolks and quail egg yolk contained more phosphotidylserine
      than either chicken or duck egg yolks. The differences in post-thaw motility and
      acrosome integrity of boar sperm when frozen in media containing the different
      types of egg yolk may be due to the variation in composition.

PMID- 16420335
TI  - Parvovirus antibodies in vaccinated gilts in field conditions--results with HI
      and ELISA tests.
AB  - This study was conducted to determine the antibody response for porcine
      parvovirus (PPV) of 39 gilts in field conditions after vaccination. Gilts from
      four herds endemically infected with PPV were injected twice with a commercial
      vaccine of inactivated PPV and Erysipelothrix rhusiopathiae. The PPV antibodies
      were analysed both with haemagglutination inhibition (HI) and enzyme-linked
      immunosorbent assay (ELISA) in order to study the agreement between these
      methods. The possible association between high-antibody titres and reproductive
      failure (repeat breeding, culling for infertility, < or = 6 piglets born alive)
      was also investigated. In these study herds, endemically infected by PPV, most
      gilts (84.6%) had not seroconverted by the age of 6 months. On-field vaccination
      resulted in a consistent increase of humoral immunity not exceeding the antibody
      level of 1 : 512 in the majority of gilts in all herds examined. The agreement
      between ELISA and HI tests was moderate (Spearman's rho = 0.87, kappa = 0.63).
      The seroconversion over the level >1:512 by mid-pregnancy was not associated with
      reproductive failure.

PMID- 16420334
TI  - Intracerebroventricular infusion of leptin into mature merino rams of different
      metabolic status: effects on blood concentrations of glucose and reproductive and
      metabolic hormones.
AB  - In mature Merino rams, nutrition is one of the external cues that most strongly
      affects the reproductive centres of the preoptic-hypothalamic continuum. The
      signalling pathways that link dietary status and the activity of the neurones
      that produce gonadotrophin-releasing hormone signals are thought to be partly
      hormonal in nature to reflect the amount of body reserves. Among the hormones
      thought to be involved are insulin and leptin. This study tested whether
      recombinant bovine leptin infused (0.4 microg/h) into the third cerebral
      ventricle would stimulate pulsatile luteinizing hormone (LH) secretion in mature
      Merino rams when their energy status was low or decreasing, during both chronic
      (fasting) and acute reductions of energy balance. Leptin may interact with other
      hormones that depend on energy availability, so we also monitored changes in
      circulating concentrations of insulin, thyroid hormones, growth hormone,
      prolactin and adrenocorticotrophin. Overall, our data do not support this
      hypothesis. The dietary regimes induced clear responses in the metabolic profiles
      of the animals but there was no clear effect of central leptin administration on
      LH pulse frequency. The relationships between the hormonal systems measured in
      the present study add weight to the contention that leptin plays only a
      permissive role in the nutritional control of the reproductive axis and that
      other hormonal signals (particularly insulin) or pathways are acting in concert
      with leptin to stimulate the reproductive axis.

PMID- 16420336
TI  - Changes in the timing of SIDS deaths in 1989 and 1999: indirect evidence of low
      homicide prevalence among reported cases.
AB  - An unknown proportion of cases diagnosed as sudden infant death syndrome (SIDS)
      are misdiagnosed, and in some cases are homicides. Because recent SIDS prevention
      measures were unlikely to reduce homicides, changes in the reported timing of
      SIDS cases provide an indirect measure of covert homicides in this group. This
      paper uses United States vital statistics microdata to explore these questions.
      The sample includes all reported infant deaths to singletons with birthweight >
      500 g in the 1989 and 1999 US birth cohorts. Deaths attributed to SIDS (n =
      7708), homicide (n = 597), or object inhalation and mechanical suffocation (n =
      860) are specifically examined. If reported SIDS cases were a mixture of 'true'
      cases and misdiagnosed homicides, it is hypothesised that the age-at-death
      distribution of SIDS deaths would have changed to reflect greater prevalence of
      misdiagnosed homicide. We find that the age-at-death distribution of reported
      SIDS cases was virtually unchanged in the two cohorts, showing no increase during
      periods of infancy when relative homicide risk is most pronounced. One cannot
      reject the hypothesis that the timing was drawn from the same distribution
      (chi2(52)= 62.2, P = 0.157). Analogous results hold for infants born in
      circumstances associated with high homicide risk (chi2(50) = 61.5, P = 0.12). The
      stable age-at-death distribution of reported SIDS cases between 1989 and 1999
      suggests that covert homicides are a small fraction of reported SIDS cases.

PMID- 16420337
TI  - Social class inequalities in childhood mortality and morbidity in an English
      population.
AB  - The objective of this study was to examine the association between social class
      of the head of household at the time of birth and mortality and morbidity during
      the first 10 years of life in a cohort of all 117 212 children born to women who
      both lived, and delivered in hospital, in Oxfordshire or West Berkshire during
      the period 1 January 1979 to 31 December 1988. Logistic regression was used to
      estimate social class gradients, with odds ratios (OR), for mortality during the
      early neonatal period, late neonatal period, post-neonatal period, post-infancy
      period and throughout the first 10 years of life. Logistic regression was also
      used to estimate social class gradients, with ORs, for hospital admission rates
      for 16 broad groups of diseases during years 0-3, 4-6, 7-10 and throughout the
      first 10 years of life. Poisson regression was used to estimate social class
      gradients, with effect sizes, for overall hospital admission rates during years 0
      3, 4-6, 7-10 and throughout the first 10 years of life. The study revealed a
      significant social class gradient in mortality during the first 10 years of life
      (adjusted OR for each decrement in social class category 1.08; [95% confidence
      interval 1.03, 1.14]). The study also revealed a significant adjusted social
      class gradient in hospital admission rates for 14 of the 16 groups of diseases
      during the first 10 years of life. For the majority of these, the social class
      gradients had attenuated somewhat by the later childhood years. However, the
      social class gradient persisted throughout the first 10 years of life for
      diseases of the respiratory system (1.07 [1.05, 1.08]), diseases of the digestive
      system (1.06 [1.04, 1.09]), and injury and poisoning (1.07 [1.06, 1.09]). In
      addition, a significant adjusted social class gradient was found in overall
      hospital admission rates for each age group studied. This study suggests that
      there are significant social class inequalities in a wide range of adverse child
      health outcomes.

PMID- 16420338
TI  - A comparison of morbidity rates attributable to conditions originating in the
      perinatal period among newborns discharged from United States hospitals, 1989-90
      and 1999-2000.
AB  - Perinatal conditions account for 60% of US neonatal deaths, yet little is known
      about rates of morbidity attributable to these conditions. To estimate these
      rates, we analysed newborn hospital discharges from the National Hospital
      Discharge Survey. We used International Classification of Diseases, 9th Revision,
      Clinical Modification (ICD-9-CM) codes to classify discharge diagnoses among a
      weighted, nationally representative sample of newborns discharged from short
      stay, non-federal US hospitals. We compared overall and cause-specific morbidity
      rates attributable to perinatal conditions (ICD-9-CM 760.0-779.9), as well as the
      average length of hospital stay among newborn discharges during 1989-90 and 1999
      2000. The overall newborn morbidity rate declined from 36.3% in 1989-90 to 33.7%
      in 1999-2000 (P < 0.01), despite significant increases in high-risk births. The
      decline can be attributed to significant decreases in the reported rates of
      jaundice, fetal distress, birth trauma and birth asphyxia. Rates of jaundice
      decreased from 15.7% to 13.4% (P < 0.01). The average length of stay decreased
      among newborns with no morbid condition (2.37-2.04 days, P < 0.001) and among
      those with one perinatal condition (3.11-2.51, P < 0.001), but increased among
      those with multiple perinatal conditions (8.43-9.98, P < 0.05). Morbidity rates
      among newborns discharged from US hospitals declined. Shorter newborn hospital
      stays may have resulted in fewer cases of jaundice being diagnosed before
      discharge. Stricter diagnostic criteria and changes in obstetric practices may
      have led to a decline in the rates of fetal distress, birth trauma and birth
      asphyxia.

PMID- 16420340
TI  - A population-based case-control study of risk factors for neural tube defects in
      four high-prevalence areas of Shanxi province, China.
AB  - Shanxi province in Northern China has one of the highest reported prevalence
      rates of neural tube defects (NTD) in the world. To explore the risk factors for
      NTDs in Shanxi province, we carried out a population-based case-control study in
      four selected counties with prevalence rates >10 per 1000 births during 2003.
      Using a multi-logistic regression model analysis (alpha = 0.10), 158 NTD cases
      were compared with 226 control mothers. Maternal factors significantly associated
      with increased risk for an NTD were a primary school education or lower (adjusted
      odds ratio [OR] 2.32, 95% confidence interval [CI] 1.09, 4.97); a history of a
      previous birth defect-affected pregnancy (adjusted OR 5.27, 95% CI 0.98, 28.37);
      history of a fever or 'cold' (adjusted OR 3.36, 95% CI 1.68, 6.72); use of
      analgesic and antipyretic drugs (adjusted OR 4.89, 95% CI 0.92, 25.97); daily
      passive exposure to cigarette smoke (adjusted OR 1.60, 95% CI 0.94, 2.73); poor
      ventilation during heating (adjusted OR 3.91, 95% CI 0.75, 20.81); and
      consumption of >or= six meals per week containing pickled vegetables (adjusted OR
      3.86, 95% CI 1.11, 13.47) during pregnancy. Factors which appeared to be
      protective were meat consumption one to three times per week (adjusted OR 0.62,
      95% CI 0.37, 1.06), or >or= four times per week (adjusted OR 0.28, 95% CI 0.11,
      0.77); and legume consumption >or= six times per week (adjusted OR 0.39, 95% CI
      0.17, 0.89). Differences in risk were found between the two most common
      phenotypes, anencephaly and spina bifida. Most of the environmental factors had
      stronger positive and negative associations with risk for anencephaly rather than
      spina bifida, whereas history of a previous birth defect-associated pregnancy, as
      well as legume consumption, were more strongly associated with the risk for spina
      bifida than for anencephaly. The findings suggest that aetiological heterogeneity
      may exist between anencephaly and spina bifida.

PMID- 16420339
TI  - Changes in dietary intake from the first to the second trimester of pregnancy.
AB  - Maternal diet may influence outcomes of pregnancy and childhood. Diet in the
      first trimester may be more important to development and differentiation of
      various organs, whereas diet later in pregnancy may be important for overall
      fetal growth as well as for brain development. To our knowledge, no studies have
      examined individual-level changes in food and nutrient intake from the 1st to 2nd
      trimester of pregnancy. The objective of this study was to examine changes in
      dietary intake from the 1st to 2nd trimester of pregnancy. As part of the ongoing
      US prospective cohort study, Project Viva, we studied 1543 women who completed
      food-frequency questionnaires that assessed dietary intakes during the 1st and
      2nd trimester of pregnancy. For both foods and energy-adjusted nutrients, we
      examined changes in dietary intake from 1st to 2nd trimester. Reported mean
      energy intake was similar for the 1st (2046 kcal) and 2nd (2137 kcal) trimesters.
      Foods and energy-adjusted nutrients from foods whose overall mean intakes
      increased more than 5% from 1st to 2nd trimester were skim or 1% dairy foods
      (22%), whole-fat dairy foods (15%), red and processed meat (11%), saturated fat
      (6%) and vitamin D (7%). Intake of caffeinated beverages (-30%) and alcoholic
      beverages (-88%) decreased more than 5%. Because mean multivitamin intake
      increased by 35% from the 1st to 2nd trimester, total micronutrient intake
      increased appreciably more than micronutrient intake from foods only.
      Correlations across trimesters ranged from 0.32 for vitamin B12 to 0.68 for fruit
      and vegetables. In conclusion, for many outcomes of pregnancy and childhood, the
      incremental information obtained from assessing complete diet in both early and
      late pregnancy may not outweigh the burden to participants and investigators.
      However, investigators should assess caffeine, alcohol, and vitamin and
      supplement use in both the 1st and 2nd trimester, and consider doing so for foods
      and nutrients for which trimester-specific hypotheses are well substantiated.

PMID- 16420341
TI  - Descriptive epidemiology of teratoma in infants, Hawaii, 1986-2001.
AB  - Although teratoma is the most common type of neonatal tumour, there are few
      population-based epidemiological data on teratoma among infants. Using data from
      a population-based birth defects registry in Hawaii, this study described the
      distribution of teratoma with respect to various demographic and clinical
      factors. A total of 22 cases were identified among deliveries in 1986-2001, of
      which 13 (59.1%) were located in the sacrococcygeal region. The rate per 10 000
      live births was 0.74 for all cases and 0.43 for sacrococcygeal cases. Major birth
      defects were identified in 7 (31.8%) of the cases. Females accounted for 57.1% of
      all cases and 58.3% of sacrococcygeal cases. Teratoma rates were highest for
      Pacific Islanders (1.08) and lowest for Far East Asians (0.37) and Filipinos
      (0.72). The rate was higher in metropolitan Honolulu (0.89) than in the rest of
      Hawaii (0.62). Teratoma rates were greater with gestational age < 38 weeks (2.15)
      than for gestational age >or= 38 weeks (0.34). No clear differences in rates were
      identified with respect to maternal age, birthweight and plurality. Except for
      gestational age, the rate differences were not statistically significant. In
      conclusion, this study found that most of the teratomas among infants occur in
      the sacrococcygeal region. Differences in teratoma rates were noted with respect
      to sex, maternal race/ethnicity, geography and gestational age. Due to the small
      number of cases, caution should be used when interpreting the results. Further
      investigation involving larger data sets is recommended.

PMID- 16420342
TI  - Early onset dactylitis associated with the occurrence of severe events in
      children with sickle cell anaemia. The Paediatric Cohort of Guadeloupe (1984-99).
AB  - Dactylitis or hand-foot syndrome is related to intravascular sickling and
      classically occurs around 6 months of life when haemoglobin S levels reach
      pathological significance. It has been hypothesised as a possible predictive
      factor of adverse outcome. The objective of this study was to estimate the
      survival without severe events (acute chest syndrome, stroke or death) according
      to early occurrence of dactylitis in the sickle cell paediatric cohort of
      Guadeloupe. The study period was 1 January 1984 to 31 December 1999. Medical data
      were recorded from birth for children with sickle cell anaemia diagnosed before 6
      months of age. The Kaplan-Meier method was used to estimate the severe event-free
      survival and to draw related curves. We used proportional-hazard modelling to
      assess the risk of severe events (stroke or acute chest syndrome or death) in
      children with early dactylitis (before 6 months of age). The study sample
      comprised 114 children. The incidence [95% confidence interval] of clinical
      events per 100 child-years were 10.0 [7.63, 13.07] for dactylitis, 0.73 [0.33,
      1.62] for stroke, 10.88 [8.35, 14.17] for acute chest syndrome and 1.06 [0.56,
      2.05] for death. Thirteen of the 14 children who had dactylitis before 6 months
      of age had at least one severe event later in life. The median severe event-free
      survival time was 2.1 [1.6, 2.7] years in children with dactylitis before 6
      months compared with 6.3 [4.5, 8.1] years in the other children; P < 0.0005.
      After adjustment for haemoglobin level <or=7 g/dL (25th percentile), leucocyte
      count >19 000/mm3 (75th percentile), transfusion before age of one year, acute
      splenic sequestration before the age of one year, the adjusted hazard ratio of
      severe event for children with early dactylitis was 2.13 [1.06, 4.40]; P < 0.03.
      Dactylitis occurring before 6 months of life identifies children at risk of
      severe complications who should benefit from close management.

PMID- 16420343
TI  - Measuring corticotropin-releasing hormone in pregnant women - comparing blood
      collection protocols for epidemiological studies.
AB  - We describe a pilot study to determine the effect of delays in blood sample
      processing under simulated field conditions on measurement of corticotropin
      releasing hormone (CRH) levels in pregnant women. CRH, a peptide secreted by the
      placenta into the maternal blood, is of interest in epidemiological studies of
      gestational duration. Many investigators suspected that CRH might break down
      quickly after collection, and believed the optimal treatment of blood samples for
      CRH must include immediate processing under chilled conditions and quick freezing
      of plasma. Epidemiological studies often have logistical constraints that make
      such rapid processing unfeasible. To examine how delays in the processing of
      blood samples might affect the level of measured CRH, we collected whole blood
      samples from 33 pregnant women attending a prenatal clinic in Boston. We compared
      CRH levels measured following three different processing delays with the levels
      of samples that were processed immediately after blood collection, the 'gold
      standard'. The delayed strategies involved placing the freshly collected whole
      blood in a cooler or refrigerator for up to 22 h prior to processing. Correlation
      coefficients comparing delayed with gold standard processing exceeded 0.96. These
      results suggest that CRH may be measured in blood samples that were spun and
      frozen up to 22 h after blood collection.

PMID- 16420344
TI  - Methodological challenges in studying labour progression in contemporary
      practice.
AB  - In the 1950s, Emanuel Friedman described the first comprehensive method of
      evaluating labour in clinical practice. In this landmark work, Friedman described
      the relationship between the duration of labour and cervical dilation as a
      sigmoid curve and outlined a tool for following labour progression and for
      identifying abnormal labour. His definitions of labour protraction and arrest
      continue to be applied in contemporary obstetric practice, although there have
      been considerable changes since in the clinical management of labour and
      delivery. This paper provides an overview of Friedman's work, addresses various
      methodological challenges in studying labour progression, and describes the
      utility of more advanced statistical methods for studying labour progression,
      such as survival analysis, compared with other approaches. Additional research
      that utilises and refines such methods will provide greater insight into labour
      progression and may assist in updating the diagnostic criteria for labour
      protraction and arrest disorders in contemporary obstetric practice. Moreover,
      such detailed information could have important clinical implications towards
      reducing the rate of primary caesarean delivery in the United States.

PMID- 16420345
TI  - Reproducibility of assays for steroid hormones, prolactin and insulin-like growth
      factor-1 in umbilical cord blood.
AB  - We assessed the reproducibility of measurements of plasma hormone and binding
      protein levels in umbilical cord blood collected from 30 male and female babies.
      They were delivered as singleton births from full-term pregnancies (gestational
      age >or= 37 weeks) in a cord blood donation programme. We assayed three plasma
      replicates from each cord blood sample at two points in time. Plasma oestradiol,
      unconjugated oestriol, testosterone, progesterone, prolactin, sex-hormone binding
      globulin (SHBG), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3
      (IGFBP-3) levels were measured in duplicates in the same batch (batch 1). In
      addition, another set of assays was conducted for each cord blood 1 year apart in
      a different batch (batch 2). Means and standard deviations for each hormone and
      binding protein were similar in replicates assayed in batch 1 and 2. Pearson's
      correlation coefficients were 0.9 or higher in duplicates assayed in batch 1. The
      correlation coefficients were between 0.77 and 0.96 for between-batch assays.
      Intra-class correlation coefficients (ICC) were higher than 0.9 for assay of SHBG
      [95% CI 0.92, 1.0] and progesterone [95% CI 0.87, 0.97] and between 0.8 and 0.9
      for assay of oestradiol, unconjugated oestriol, prolactin, IGF-1, and IGFBP-3.
      The lowest ICC value was found for testosterone (ICC = 0.74; [95% CI 0.56, 1.0]).
      These data indicate a high reproducibility of cord blood hormone measurements;
      minimal differences were observed between the calibrated and the original
      regression coefficients for the association of hormones/binding proteins with
      percent of CD34+ cells in mononuclear cells.

PMID- 16420346
TI  - Growth inhibition mediated by excess negative supercoiling: the interplay between
      transcription elongation, R-loop formation and DNA topology.
AB  - It has been known for a long time that supercoiling can affect gene expression at
      the level of promoter activity. Moreover, the results of a genome-wide analysis
      have recently led to the proposal that supercoiling could play a role in the
      regulation of gene expression at this level by acting as a second messenger,
      relaying environmental signals to regulatory networks. Although evidence is
      lacking for a regulatory role of supercoiling following transcription initiation,
      recent results from both yeast and bacteria suggest that the effect of
      supercoiling on gene expression can be considerably more dramatic after this
      initiation step. Transcription-induced supercoiling and its associated R-loops
      seem to be involved in this effect. In this context, one major function of
      topoisomerases would be to prevent the generation of excess negative supercoiling
      by transcription elongation, to inhibit R-loop formation and allow gene
      expression. This function would be especially evident when substantial and rapid
      gene expression is required for stress resistance, and it may explain, at least
      in part, why topoisomerase I synthesis is directed from stress-induced promoters
      in Escherichia coli. Growth inhibition mediated by excess negative supercoiling
      might be related to this interplay between transcription elongation and
      supercoiling.

PMID- 16420347
TI  - Morphogenetic surfactants and their role in the formation of aerial hyphae in
      Streptomyces coelicolor.
AB  - Withstanding environmental adversity and seeking optimal conditions for
      reproduction are basic requirements for the survival of all organisms.
      Filamentous bacteria of the genus Streptomyces produce a remarkable cell type
      called the aerial hyphae that is central to its ability to meet both of these
      challenges. Recent advances have brought about a major shift in our understanding
      of the cell surface proteins that play important roles in the generation of these
      cells. Here we review our current understanding of one of these groups of
      proteins, the morphogenetic surfactants, with emphasis on the SapB protein of
      Streptomyces coelicolor.

PMID- 16420348
TI  - ATP- and NAD+-dependent DNA ligases share an essential function in the halophilic
      archaeon Haloferax volcanii.
AB  - DNA ligases join the ends of DNA molecules during replication, repair and
      recombination. ATP-dependent ligases are found predominantly in the eukarya and
      archaea whereas NAD+-dependent DNA ligases are found only in the eubacteria and
      in entomopoxviruses. Using the genetically tractable halophile Haloferax volcanii
      as a model system, we describe the first genetic analysis of archaeal DNA ligase
      function. We show that the Hfx. volcanii ATP-dependent DNA ligase family member,
      LigA, is non-essential for cell viability, raising the question of how DNA
      strands are joined in its absence. We show that Hfx. volcanii also encodes an
      NAD+-dependent DNA ligase family member, LigN, the first such enzyme to be
      identified in the archaea, and present phylogenetic analysis indicating that the
      gene encoding this protein has been acquired by lateral gene transfer (LGT) from
      eubacteria. As with LigA, we show that LigN is also non-essential for cell
      viability. Simultaneous inactivation of both proteins is lethal, however,
      indicating that they now share an essential function. Thus the LigN protein
      acquired by LGT appears to have been co-opted as a back-up for LigA function,
      perhaps to provide additional ligase activity under conditions of high genotoxic
      stress.

PMID- 16420349
TI  - Farnesol-induced apoptosis in Aspergillus nidulans reveals a possible mechanism
      for antagonistic interactions between fungi.
AB  - The dimorphic fungus Candida albicans secretes farnesol, which acts as a quorum
      sensing molecule and prevents the yeast to mycelium conversion. In this study we
      examined the effect of farnesol in the filamentous fungus Aspergillus nidulans.
      We show that externally added farnesol has no effect on hyphal morphogenesis;
      instead, it triggers morphological features characteristic of apoptosis.
      Additional experiments suggest that mitochondria and reactive oxygen species
      (ROS) participate in farnesol-induced apoptosis. Moreover, the effects of
      farnesol appear to be mediated by the FadA heterotrimeric G protein complex.
      Because A. nidulans does not secrete detectable amounts of farnesol, we propose
      that it responds to farnesol produced by other fungi. In agreement with this
      notion, growth and development were impaired in a farnesol-dependent manner when
      A. nidulans was co-cultivated with C. albicans. Taken together, our data suggest
      that farnesol, in addition to its quorum-sensing function that regulates
      morphogenesis, is also employed by C. albicans to reduce competition from other
      microbes.

PMID- 16420350
TI  - Defects in N-glycosylation induce apoptosis in yeast.
AB  - N-glycosylation in the endoplasmic reticulum is an essential protein modification
      and highly conserved in evolution from yeast to man. Defects of N-glycosylation
      in humans lead to congenital disorders. The pivotal step of this pathway is the
      transfer of the evolutionarily conserved lipid-linked core-oligosaccharide to the
      nascent polypeptide chain, catalysed by the oligosaccharyltransferase. One of its
      nine subunits, Ost2, has homology to DAD1, originally characterized in hamster
      cells as a defender against apoptotic death. Here we show that ost mutants, such
      as ost2 and wbp1-1, display morphological and biochemical features of apoptosis
      upon induction of the glycosylation defect. We observe nuclear condensation, DNA
      fragmentation as well as externalization of phosphatidylserine. We also
      demonstrate induction of caspase-like activity, both determined by flow
      cytometric analysis and in cell-free extracts. Similarly, the N-glycosylation
      inhibitor tunicamycin in combination with elevated temperature is able to
      challenge the apoptotic cascade. Heterologous expression of anti-apoptotic human
      Bcl-2 diminishes caspase activation, improves survival of cells and suppresses
      the temperature-sensitive growth defect of wbp1-1. Furthermore, accumulation of
      reactive oxygen species occurs in response to defective glycosylation. As
      deletion of the metacaspase YCA1 does not seem to abrogate glycosylation-induced
      apoptosis, we postulate a different proteolytic process to be involved in this
      death pathway.

PMID- 16420351
TI  - Organization of ETRAMPs and EXP-1 at the parasite-host cell interface of malaria
      parasites.
AB  - The parasite-host cell interface is a key compartment of vacuolated intracellular
      pathogens but little is known about its molecular composition and architecture.
      We used in vivo cross-linking to analyse the parasite-host cell interface of
      asexual stages of the most virulent human malaria parasite Plasmodium falciparum.
      We show that the integral membrane protein members of the early transcribed
      membrane protein (ETRAMP) family and exported protein 1 (EXP-1), which are
      components of the parasite-host cell interface, form complexes of oligomeric
      arrays in this compartment. The most notable feature is that each ETRAMP member
      and EXP-1 define separate arrays, demonstrating that the protein distribution in
      this membrane is non-random. Each of three recombinant ETRAMPs readily
      oligomerized in bacterial membranes, confirming that these arrays can form
      independently of other Plasmodium proteins. We propose that the malaria parasite
      host cell interface contains patches of integral membrane proteins forming a
      mosaic of different microdomains in this membrane.

PMID- 16420352
TI  - The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S
      adenosylmethionine.
AB  - The Elp3 subunit of the Elongator complex is highly conserved from archaea to
      humans and contains a well-characterized C-terminal histone acetyltransferase
      (HAT) domain. The central region of Elp3 shares significant sequence homology to
      the Radical SAM superfamily. Members of this large family of bacterial proteins
      contain a FeS cluster and use S-adenosylmethionine (SAM) to catalyse a variety of
      radical reactions. To biochemically characterize this domain we have expressed
      and purified the corresponding fragment of the Methanocaldococcus jannaschii Elp3
      protein. The presence of a Fe4S4 cluster has been confirmed by UV-visible
      spectroscopy and electron paramagnetic resonance (EPR) spectroscopy and the Fe
      content determined by both a colorimetric assay and atomic absorption
      spectroscopy. The cysteine residues involved in cluster formation have been
      identified by site-directed mutagenesis. The protein binds SAM and the binding
      alters the EPR spectrum of the FeS cluster. Our results provide biochemical
      support to the hypothesis that Elp3 does indeed contain the Fe4S4 cluster which
      characterizes the Radical SAM superfamily and binds SAM, suggesting that Elp3, in
      addition to its HAT activity, has a second as yet uncharacterized catalytic
      function. We also present preliminary data to show that the protein cleaves SAM.

PMID- 16420354
TI  - Different signalling pathways involving a Galpha protein, cAMP and a MAP kinase
      control germination of Botrytis cinerea conidia.
AB  - Conidial germination of the grey mould fungus Botrytis cinerea was found to be
      induced by different chemical and physical signals, namely the amount and quality
      of nutrients as well as the hydrophobicity and rigidity of the surface. A B.
      cinerea Deltabcg3 mutant disrupted in the Galpha3 subunit of the heterotrimeric G
      protein was specifically defective in germination induced by carbon sources. A
      similar germination defect of an adenylate cyclase mutant, and the complementing
      effect of cAMP addition to conidia of these mutants confirmed the involvement of
      cAMP. In contrast, a Deltabmp1 MAP kinase mutant was delayed in carbon source
      induced germination, but completely unable to germinate on hydrophobic surfaces.
      Based on these data, it is proposed that the germination response of B. cinerea
      conidia is controlled by three signalling pathways: Germination induction by rich
      media is weakly dependent on BMP1; induction by carbon sources requires BCG3,
      cAMP and BMP1; and induction by contact to hydrophobic surfaces is absolutely
      dependent on BMP1. Other defects of the Deltabcg3 mutant, such as low
      conidiation, excessive formation of sclerotia and delayed host infection, were
      also restored by cAMP. Microscopical studies of germling growth and
      differentiation on host cuticles revealed that the delayed infection of the
      Deltabcg3 mutant was due to a surface sensing defect leading to a reduced
      penetration. Thus, in addition to their role in germination, Galpha3, cAMP as
      well as BMP1 are required also for proper host surface recognition and
      penetration ability of germinated conidia.

PMID- 16420353
TI  - Metabolic regulation of type III secretion gene expression in Pseudomonas
      aeruginosa.
AB  - Type III secretion-mediated cytotoxicity is one of the key virulence mechanisms
      of the opportunistic pathogen Pseudomonas aeruginosa. Prior data from several
      laboratories have established that metabolism is a key factor in the regulation
      of type III secretion gene expression in P. aeruginosa. Here we use a
      fluorescence-activated cell sorter (FACS)-based approach to investigate
      expression of type III secretion genes at a single-cell level. The data
      demonstrate that the metabolic state regulates the percentage of cells that are
      able to induce type III secretion gene expression under inducing conditions. We
      also present evidence that this regulation is the result of an effect of the
      growth conditions on the ability of P. aeruginosa to assemble a functional type
      III secretion apparatus. Preliminary data suggest that the metabolite that
      controls type III secretion gene expression is derived from acetyl-CoA and that
      this regulation may, in part, be mediated by changes in the intracellular
      concentration of cyclic-AMP.

PMID- 16420355
TI  - Synthesis of alpha-glucans in fission yeast spores is carried out by three alpha
      glucan synthase paralogues, Mok12p, Mok13p and Mok14p.
AB  - Fission yeast possesses a family of (1,3)-alpha-glucan synthase-related genes;
      one of them, mok1+/ags1+, plays an essential function in morphogenesis during
      vegetative growth. Here we show that three mok1+ paralogues -mok12+, mok13+ and
      mok14+- are required for sporulation to succeed, acting at different stages of
      the spore wall maturation process. Mutation of mok12+ affected the efficiency of
      spore formation and spore viability. Deletion of mok13+ does not affect spore
      viability but the spores showed reduced resistance to stress conditions.
      mok14Delta mutant spores failed to accumulate the amylose-like spore wall
      specific polymer. mok12+, mok13+ and mok14+ expression was restricted to
      sporulating cells and the proteins localized to the spore envelope but with
      different timing. mok11+ was also induced during the sporulation process although
      its deletion did not show apparently a sporulation defect. In vegetative cells,
      beta-glucans are more abundant than alpha-glucans (55% versus 28%). In spores,
      the situation was the opposite, alpha-glucans accounted for 46% while beta
      glucans were approximately 38% of the total polysaccharides. We found at least
      two types of alpha-glucan polymers, Mok12p and Mok13p, were involved in the
      synthesis of the greater part of alpha-glucan in the spores envelope, a polymer
      that is mainly digested with alpha-1,3 glucanase, while Mok14p, homologous to
      starch synthases, was required for the synthesis of the iodine-reactive polymer
      that is made of alpha-1,4 glucose residues.

PMID- 16420356
TI  - TmpA, a member of a novel family of putative membrane flavoproteins, regulates
      asexual development in Aspergillus nidulans.
AB  - Asexual reproduction (conidiation) in Aspergillus nidulans is induced by
      environmental signals like exposure to air or nutrient starvation, and depends on
      brlA gene activation. The study of 'fluffy' mutants showing delayed asexual
      development and reduced brlA expression has defined the fluG pathway, involved in
      regulation of this differentiation process. Genetic characterization of a
      'fluffy' mutant identified tmpA as a new gene involved in regulation of
      conidiation. TmpA defines a new family of putative transmembrane proteins of
      unknown function, widespread in filamentous fungi and plants, with homologues
      showing similarity to non-ribosomal peptide synthetases. The deletion of tmpA
      resulted in decreased brlA expression and conidiation in air-exposed colonies.
      This defect was suppressed when DeltatmpA mutants were grown next to wild-type or
      DeltafluG mutant colonies, even without direct contact between hyphae. In liquid
      culture, tmpA was essential for conidiation induced by nitrogen but not by carbon
      starvation, whereas the overexpression of different tmpA tagged alleles resulted
      in conidiation. The overexpression of fluG-induced conidiation independently of
      tmpA and DeltatmpADeltafluG double mutants showed an additive 'fluffy' phenotype,
      indicating that tmpA and fluG regulate asexual sporulation through different
      pathways. TmpA and its homologues appear to have diverged from the ferric
      reductase family, retaining overall transmembrane architecture, NAD(P), flavin
      adenine dinucleotide (FAD) and possibly haem-binding domains. Based on our
      results, we propose that TmpA is a membrane oxidoreductase involved in the
      synthesis of a developmental signal.

PMID- 16420357
TI  - Secretion of curli fibre subunits is mediated by the outer membrane-localized
      CsgG protein.
AB  - Produced by many Enterobacteriaceae spp., curli are biologically important
      amyloid fibres that have been associated with biofilm formation, host cell
      adhesion and invasion, and immune system activation. CsgA is the major fibre
      subunit and CsgE, CsgF and CsgG are non-structural proteins involved in curli
      biogenesis. We have characterized the role of CsgG in curli subunit secretion
      across the outer membrane. Directed mutagenesis of CsgG confirmed that its
      activity is dependent on localization to the outer membrane. Rotary Shadow
      electron microscopy of purified CsgG suggested that this protein assembles into
      an oligomeric complex with an apparent central pore. Oligomeric CsgG complexes
      were confirmed using co-purification experiments. Antibiotic sensitivity assays
      demonstrated that overexpression of CsgG rendered Escherichia coli susceptible to
      the antibiotic erythromycin. A 22-amino-acid sequence at the N-terminus of CsgA
      was sufficient to direct heterologous proteins to the CsgG secretion apparatus.
      Finally, we determined that CsgG participates in an outer membrane complex with
      two other curli assembly proteins, CsgE and CsgF.

PMID- 16420358
TI  - Oxylipins act as determinants of natural product biosynthesis and seed
      colonization in Aspergillus nidulans.
AB  - Secreted, hormone-like lipogenic molecules, called oxylipins, mediate the balance
      of asexual to sexual spore ratio in Aspergillus nidulans. Oxylipin production in
      this fungus is dependent on developmental regulation of three conserved fatty
      acid oxygenases, PpoA, PpoB and PpoC. Here, we show that in addition to altering
      spore ratios, loss of ppo genes affect natural product biosynthesis and seed
      colonization. DeltappoA;DeltappoC and DeltappoA;DeltappoB;DeltappoC mutants were
      unable to produce the mycotoxin sterigmatocystin (ST) in vitro or in planta but
      in contrast overproduced the antibiotic penicillin (PN). These findings were
      correlated with decreased expression of genes involved in ST biosynthesis and
      increased expression of a PN biosynthetic gene, thus suggesting that oxylipin
      species regulate secondary metabolites at the transcriptional level.
      Additionally, the DeltappoA;DeltappoC and the DeltappoA;DeltappoB;DeltappoC
      mutants were defective in colonization of peanut seeds as reflected by a decrease
      in conidiation and production of the seed degradative enzyme lipase. These
      results indicate that oxylipin production is important for host colonization and
      mycotoxin production and may provide a promising target for future control
      strategies.

PMID- 16420359
TI  - A mannan binding lectin is involved in cell-cell attachment in a toxic strain of
      Microcystis aeruginosa.
AB  - Microcystin, a hepatotoxin that represents a serious health risk for humans and
      livestock, is produced by the bloom-forming cyanobacterium Microcystis aeruginosa
      in freshwater bodies worldwide. Here we describe the discovery of a lectin,
      microvirin (MVN), in M. aeruginosa PCC7806 that shares 33% identity with the
      potent anti-HIV protein cyanovirin-N from Nostoc ellipsosporum. Carbohydrate
      microarrays were employed to demonstrate the high specificity of the protein for
      high-mannose structures containing alpha(1-->2) linked mannose residues. Lectin
      binding analyses and phenotypic characterizations of MVN-deficient mutants
      suggest that MVN is involved in cell-cell recognition and cell-cell attachment of
      Microcystis. A binding partner of MVN was identified in the lipopolysaccharide
      fraction of M. aeruginosa PCC7806. MVN is differentially expressed in mutants
      lacking the hepatotoxin microcystin. Additionally, MVN-deficient mutants contain
      much lower amounts of microcystin than the wild-type cells. We discuss a possible
      functional correlation between microcystin and the lectin and possible
      implications on Microcystis morphotype formation. This study provides the first
      experimental evidence that microcystins may have an impact on Microcystis colony
      formation that is highly important for the competitive advantage of Microcystis
      over other phytoplankton species.

PMID- 16420360
TI  - The cell surface expression of group 2 capsular polysaccharides in Escherichia
      coli: the role of KpsD, RhsA and a multi-protein complex at the pole of the cell.
AB  - The export of large negatively charged capsular polysaccharides across the outer
      membrane represents a significant challenge to Gram negative bacteria. In the
      case of Escherichia coli group 2 capsular polysaccharides, the mechanism of
      export across the outer membrane was unknown, with no identified candidate outer
      membrane proteins. In this paper we demonstrate that the KpsD protein, previously
      believed to be a periplasmic protein, is an outer membrane protein involved in
      the export of group 2 capsular polysaccharides across the outer membrane. We
      demonstrate that KpsD and KpsE are located at the poles of the cell and that
      polysaccharide biosynthesis and export occurs at these polar sites. By in vivo
      chemical cross-linking and MALDI-TOF-MS analysis we demonstrate the presence of a
      multi-protein biosynthetic/export complex in which cytoplasmic proteins involved
      in polysaccharide biosynthesis could be cross-linked to proteins involved in
      export across the inner and outer membranes. In addition, we show that the RhsA
      protein, of previously unknown function, could be cross-linked to the complex and
      that a rhsA mutation reduces K5 biosynthesis suggesting a role for RhsA in
      coupling biosynthesis and export.

PMID- 16420361
TI  - The vancomycin resistance VanRS two-component signal transduction system of
      Streptomyces coelicolor.
AB  - We took advantage of the vancomycin-dependent phenotype of Streptomyces
      coelicolor femX null mutants to isolate a collection of spontaneous, drug
      independent femX suppressor mutants that expressed the vancomycin-resistance
      (van) genes constitutively. All of the suppressor mutations were in vanS but,
      unexpectedly, many were predicted to be loss-of-function mutations. Confirming
      this interpretation, a constructed vanS deletion mutation also resulted in
      constitutive expression of the van genes, suggesting that VanS negatively
      regulated VanR function in the absence of drug. In contrast, a vanS pta ackA
      triple mutant, which should not be able synthesize acetyl phosphate, failed to
      express the van genes, whereas a pta ackA double mutant showed wild-type,
      regulated induction of the van genes. These results suggest that in the absence
      of vancomycin, acetyl phosphate phosphorylates VanR, and VanS acts as a
      phosphatase to suppress the levels of VanR approximately P. On exposure to
      vancomycin, VanS activity switches from a phosphatase to a kinase and vancomycin
      resistance is induced. In S. coelicolor, the van genes are induced by both
      vancomycin and the glycopeptide A47934, whereas in Streptomyces toyocaensis (the
      A47934 producer) resistance is induced by A47934 but not by vancomycin. We
      exploited this distinction to replace the S. coelicolor vanRS genes with the
      vanRS genes from S. toyocaensis. The resulting strain acquired the inducer
      profile of S. toyocaensis, providing circumstantial evidence that the VanS
      effector ligand is the drug itself, and not an intermediate in cell wall
      biosynthesis that accumulates as result of drug action. Consistent with this
      suggestion, we found that non-glycopeptide inhibitors of the late steps in cell
      wall biosynthesis such as moenomycin A, bacitracin and ramoplanin were not
      inducers of the S. coelicolor VanRS system, in contrast to results obtained in
      enterococcal VanRS systems.

PMID- 16420362
TI  - Anti-phagocytic mechanisms of Streptococcus pyogenes: binding of fibrinogen to M
      related protein.
AB  - A key attribute of invasive Streptococcus pyogenes is their ability to resist
      phagocytosis and multiply in human blood. M-related protein (Mrp) is a major anti
      phagocytic factor but the mechanism whereby it helps streptococci to evade
      phagocytosis has not been demonstrated. We investigated phagocytosis resistance
      in a strain of serotype M4 by inactivating the mrp gene and also the emm, enn,
      sof and sfbX genes and by analysing the effect on streptococcal growth in blood
      and on complement deposition on the bacterial surface. Inactivation of enn4 and
      sfbX4 had little impact on growth in blood, but ablation of mrp4, emm4 or sof4
      reduced streptococcal growth in human blood, confirming that Mrp and Emm are
      required for optimal resistance to phagocytosis and providing the first
      indication that Sof may be an anti-phagocytic factor. Moreover, antisera against
      Mrp4, Emm4 and Sof4 promoted the killing of S. pyogenes, but anti-SfbX serum had
      no effect. Growth of S. pyogenes in blood was dependent on the presence of
      fibrinogen and in the absence of fibrinogen there was a twofold increase in
      complement deposition. Inactivation of mrp4 resulted in a loss of fibrinogen
      binding and caused a twofold increase in the binding of C3b that was inhibited by
      Mg-EGTA. Mrp contained two fibrinogen-binding sites, one of which is within a
      highly conserved region. These findings indicate that Mrp-fibrinogen interactions
      prevent surface deposition of complement via the classical pathway, thereby
      contributing to the ability of these streptococci to resist phagocytosis. This
      may be a common mechanism for evasion of phagocytosis because Mrp is expressed by
      approximately half of the clinical isolates of S. pyogenes.

PMID- 16420363
TI  - Molecular characterization of the capsule locus from non-typeable Staphylococcus
      aureus.
AB  - Most Staphylococcus aureus express a serotype 5 or 8 capsular polysaccharide
      (CP). However, 20-25% of human isolates and up to 86% of bovine strains of S.
      aureus are non-typeable (NT), i.e. non-reactive with antibodies to CP types 1, 2,
      5 or 8. A vaccine that targets the S. aureus CP would not protect against NT
      strains. The aim of this study was to characterize NT S. aureus isolates at the
      molecular level to explain their lack of type 5 or 8 capsule production. The
      cap5(8) locus was present in all 22 NT clinical isolates from humans, eight of 21
      bovine isolates, and in all eight sequenced strains. NT strains positive for the
      cap5(8) transcript had mutations within essential capsule genes and could be
      complemented in trans. S. aureus strains with reduced cap5(8) transcript had
      mutations within the cap5A promoter, decreased RNAIII levels, or a truncated arlR
      gene product. More than one mutation was identified in several isolates. The
      cap5(8) locus was replaced by IS257 in 13 of 21 NT bovine isolates of S. aureus.
      Lack of capsule expression in NT S. aureus can be explained by multiple
      mechanisms, and the data argue against the existence of capsule serotypes other
      than 1, 2, 5 and 8.

PMID- 16420364
TI  - Deglycosylation of human glycoconjugates by the sequential activities of
      exoglycosidases expressed by Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae produces three surface-associated exoglycosidases; a
      neuraminidase, NanA, a beta-galactosidase, BgaA, and a beta-N
      acetylglucosaminidase, StrH. the proposed functions of NanA, which removes
      terminal sialic acid, include revealing receptors for adherence, affecting the
      function of glycosylated host clearance molecules, modifying the surface of other
      bacteria coinhabiting the same niche, and providing a nutrient source. However,
      it is unclear whether following desialylation S. pneumoniae can further
      deglycosylate human targets through the activity of BgaA or StrH. We demonstrate
      that NanA, BgaA and StrH act sequentially to remove sialic acid, galactose and N
      acetylglucosamine and expose mannose on human glycoproteins that bind to the
      pneumococcus and protect the airway. In addition, both BgaA and NanA were shown
      to contribute to the adherence of unencapsulated pneumococci, to human epithelial
      cells. Despite these findings, triple exoglycosidase mutants colonized mice as
      well as their parental strains, suggesting that any effect of these genes on
      colonization and disease may be host species-specific. These studies highlight
      the importance of considering the complete ability of S. pneumoniae to
      deglycosylate human targets and suggest that in addition to NanA, BgaA and StrH
      also contribute to pneumococcal colonization and/or pathogenesis.

PMID- 16420366
TI  - SepF, a novel FtsZ-interacting protein required for a late step in cell division.
AB  - Cell division in nearly all bacteria is initiated by polymerization of the
      conserved tubulin-like protein FtsZ into a ring-like structure at midcell. This Z
      ring functions as a scaffold for a group of conserved proteins that execute the
      synthesis of the division septum (the divisome). Here we describe the
      identification of a new cell division protein in Bacillus subtilis. This protein
      is conserved in Gram positive bacteria, and because it has a role in septum
      development, we termed it SepF. sepF mutants are viable but have a cell division
      defect, in which septa are formed slowly and with a severely abnormal morphology.
      Yeast two-hybrid analysis showed that SepF can interact with itself and with
      FtsZ. Accordingly, fluorescence microscopy showed that SepF accumulates at the
      site of cell division, and this localization depends on the presence of FtsZ.
      Combination of mutations in sepF and ezrA, encoding another Z-ring interacting
      protein, had a synthetic lethal division effect. We conclude that SepF is a new
      member of the Gram positive divisome, required for proper execution of septum
      synthesis.

PMID- 16420365
TI  - Clonal analysis reveals high rate of structural mutations in fimbrial adhesins of
      extraintestinal pathogenic Escherichia coli.
AB  - Type 1 fimbriae of Escherichia coli mediate mannose-specific adhesion to host
      epithelial surfaces and consist of a major, antigenically variable pilin subunit,
      FimA, and a minor, structurally conserved adhesive subunit, FimH, located on the
      fimbrial tip. We have analysed the variability of fimA and fimH in strains of
      vaginal and other origin that belong to one of the most prominent clonal groups
      of extraintestinal pathogenic E. coli, comprised of O1:K1-, O2:K1- and O18:K1
      based serotypes. Multiple locus sequence typing (MLST) of this group revealed
      that the strains have identical (at all but one nucleotide position) eight
      housekeeping loci around the genome and belong to the ST95 complex defined by the
      publicly available E. coli MLST database. Multiple highly diverse fimA alleles
      have been introduced into the ST95 clonal complex via horizontal transfer, at a
      frequency comparable to that of genes defining the major O- and H-antigens.
      However, no further significant FimA diversification has occurred via point
      mutation after the transfers. In contrast, while fimH alleles also move
      horizontally (along with the fimA loci), they acquire point amino acid
      replacements at a higher rate than either housekeeping genes or fimA. These FimH
      mutations enhance binding to monomannose receptors and bacterial tropism for
      human vaginal epithelium. A similar pattern of rapid within-clonal structural
      evolution of the adhesive, but not pilin, subunit is also seen, respectively, in
      papG and papA alleles of the di-galactose-specific P-fimbriae. Thus, while
      structurally diverse pilin subunits of E. coli fimbriae are under selective
      pressure for frequent horizontal transfer between clones, the adhesive subunits
      of extraintestinal E. coli are under strong positive selection (Dn/Ds > 1 for
      fimH and papG) for functionally adaptive amino acid replacements.

PMID- 16420367
TI  - Phosphorylation and functional analysis of the sporulation initiation factor
      Spo0A from Clostridium botulinum.
AB  - The initiation of sporulation in aerobic Bacillus species is regulated by the
      phosphorelay consisting of several sensor histidine kinases, the Spo0F response
      regulator, the Spo0B phosphotransferase and the Spo0A transcription factor that
      upon phosphorylation represses genes for growth and activates the developmental
      process. Clostridium species lack both Spo0F and Spo0B and the identities of the
      sensor histidine kinases are unknown. The amino acid sequence of Spo0A is highly
      conserved in Clostridium botulinum relative to Bacillus subtilis but the cloned
      C. botulinum Spo0A was unable to complement a spo0A mutant of B. subtilis for
      sporulation. However, it was able to repress the abrB gene of B. subtilis. Active
      site mutations in Spo0A still repressed, indicating this activity was independent
      of phosphorylation. An orphan sensor histidine kinase of C. botulinum appeared to
      normally phosphorylate C. botulinum Spo0A and expression of this kinase in
      combination with C. botulinum Spo0A in B. subtilis was lethal, suggesting
      phosphorylation of C. botulinum Spo0A repressed essential growth genes as a
      prerequisite to sporulation but could not compensate for this effect by inducing
      sporulation. A chimera Spo0A consisting of a B. subtilis Spo0A response regulator
      domain fused to a C. botulinum DNA-binding domain was capable of restoring
      sporulation to a spo0A mutant of B. subtilis albeit at less than wild-type
      levels. The data suggest that induction of sporulation requires interactions of
      both domains of Spo0A with other conserved proteins and despite the high
      conservation of the amino acid sequence of C. botulinum Spo0A, some of these
      interactions have been lost.

PMID- 16420368
TI  - Translation initiation with GUC codon in the archaeon Halobacterium salinarum:
      implications for translation of leaderless mRNA and strict correlation between
      translation initiation and presence of mRNA.
AB  - We have investigated whether anticodon sequence mutant of an archaeal initiator
      tRNA can initiate protein synthesis using reporter genes carrying mutations in
      the initiation codon. Halobacterium salinarum was used as the model organism and
      the bacterio-opsin gene (bop), which encodes the precursor of the protein
      component of the purple membrane protein bacterio-opsin (Bop), was chosen as the
      reporter. We demonstrate that a CAU to GAC anticodon sequence mutant of Haloferax
      volcanii initiator tRNA can initiate Bop protein synthesis using GUC as the
      initiation codon in H. salinarum. We generated four mutant bop genes, each
      carrying the AUG to GUC initiation codon mutation, with or without a compensatory
      mutation to maintain a predicted stem-loop structure at the 5'-end of the bop
      mRNA, and with or without mutations to test translation initiation at a site
      corresponding to the amino terminus of mature bacterio-opsin. H. salinarum
      chromosomal recombinants containing these mutant genes were phenotypically Pum-
      (purple membrane negative). Upon transformation with a plasmid carrying the
      mutant initiator tRNA gene, only strains designed to maintain the bop mRNA stem
      loop structure produced Bop and were phenotypically Pum+ as indicated by purple
      colony colour, and immunoblotting and spectral analysis of cell extracts. Thus
      GUC can serve as an initiation codon in archaea and the stem-loop structure in
      the bop mRNA is important for translation. Interestingly, for the same mutant
      mRNA, only transformants that produce Bop protein contain bop mRNA. These results
      suggest either a strong coupling between translation and mRNA stability or strong
      transcriptional polarity in H. salinarum.

PMID- 16420369
TI  - The C-terminal end of LpxC is required for degradation by the FtsH protease.
AB  - Lipopolysaccharide (LPS) biosynthesis is essential in Gram negative bacteria.
      LpxC, the key enzyme in LPS formation, catalyses the limiting reaction and
      controls the ratio between LPS and phospholipids. As overproduction of LPS is
      toxic, the cellular amount of LpxC must be regulated carefully. The membrane
      bound protease FtsH controls the level of LpxC via proteolysis making FtsH the
      only essential protease of Escherichia coli. We found that the chaperones DnaK
      and DnaJ co-purified with LpxC. However, degradation of LpxC was DnaK/J
      independent in contrast to turnover of the heat shock sigma factor sigma32
      (RpoH). The stability of LpxC in a bacterial one-hybrid system suggested that a
      terminus of LpxC might be important for degradation. Different LpxC truncations
      and extensions were constructed. Removal of at least five amino acids from the C
      terminus abolished degradation by FtsH in vivo. While addition of two aspartic
      acids to LpxC did not alter its half-life, the exchange of the last two residues
      against aspartic acids resulted in stabilization. All stable LpxC enzymes were
      active in vivo as assayed by their high toxicity. Our data demonstrate that the C
      terminus of LpxC contains a signal sequence necessary for FtsH-dependent
      degradation.

PMID- 16420370
TI  - Role of the spacer between the -35 and -10 regions in sigmas promoter selectivity
      in Escherichia coli.
AB  - In vitro, the sigma(s) subunit of RNA polymerase (RNAP), RpoS, recognizes nearly
      identical -35 and -10 promoter consensus sequences as the vegetative sigma70. In
      vivo, promoter selectivity of RNAP holoenzyme containing either sigma(s)
      (Esigma(s)) or sigma70 (Esigma70) seems to be achieved by the differential
      ability of the two holoenzymes to tolerate deviations from the promoter consensus
      sequence. In this study, we suggest that many natural sigma(s)-dependent
      promoters possess a -35 element, a feature that has been considered as not
      conserved among sigma(s)-dependent promoters. These -35 hexamers are mostly non
      optimally spaced from the -10 region, but nevertheless functional. A +/- 2 bp
      deviation from the optimal spacer length of 17 bp or the complete absence of a 
      35 consensus sequence decreases overall promoter activity, but at the same time
      favours Esigma(s) in its competition with Esigma70 for promoter recognition. On
      the other hand, the reduction of promoter activity due to shifting of the -35
      element can be counterbalanced by an activity-stimulating feature such as A/T
      richness of the spacer region without compromising Esigma(s) selectivity. Based
      on mutational analysis of sigma(s), we suggest a role of regions 2.5 and 4 of
      sigma(s) in sensing sub-optimally located -35 elements.

PMID- 16420371
TI  - Osmolyte-induced transcription: -35 region elements and recognition by sigma38
      (rpoS).
AB  - In order to meet osmotic challenges in the gastrointestinal tract, enteric
      bacteria rapidly accumulate salts of glutamate and other weak organic acids. The
      ensuing transcriptional activation is mediated by unknown elements at sigma38
      (rpoS)-dependent promoters. Here we identify DNA elements needed for high levels
      of transcription in the presence of salt and acetate and show that they are
      associated with the -35 regions of target promoters. Unrelated -35 region
      sequences are shown to specify maximal salt-challenged transcription at the otsB
      promoter and maximal acetate-challenged transcription at the cfa promoter.
      Mutants in sigma38 are isolated that contribute to bypassing the salt response
      and most of these cluster in a small segment corresponding to the presumptive -35
      DNA recognition determinant of the protein. Overall, the data suggest that an
      ensemble of -35 region elements exists at sigma38 promoters and these can help
      mediate responsiveness to physiological challenges through interactions involving
      region 4 of the sigma38 protein.

PMID- 16420372
TI  - Interactions between peptidoglycan and the ExeAB complex during assembly of the
      type II secretin of Aeromonas hydrophila.
AB  - Aeromonas hydrophila transports extracellular protein toxins via the type II
      secretion system, an export mechanism comprised of numerous proteins that spans
      both the inner and outer membranes. Two components of this secretion system, ExeA
      and ExeB, form a complex in the inner membrane that functions to locate and/or
      assemble the ExeD secretin in the outer membrane. In the studies reported here,
      two-codon insertion mutagenesis of exeA revealed that an insertion at amino acid
      495 in the C-terminal region of ExeA did not alter ExeAB complex formation yet
      completely abrogated its involvement in ExeD secretin assembly and thus rendered
      the bacteria secretion negative. In silico analysis of protein motifs with
      similar amino acid profiles revealed that this amino acid is located within a
      putative peptidoglycan (PG) binding motif in the periplasmic domain of ExeA.
      Substitution mutations of three highly conserved amino acids in the motif were
      constructed. In cells expressing each of these mutants, the ability to assemble
      the ExeD secretin or secrete aerolysin was lost, while ExeA retained the ability
      to form a complex with ExeB. In in vivo cross-linking experiments, wild-type ExeA
      could be cross-linked to PG, whereas the three substitution mutants of ExeA could
      not. These data indicate that PG binding and/or remodelling plays a role in the
      function of the ExeAB complex during assembly of the ExeD secretin.

PMID- 16420374
TI  - Morphological characterization of GFP stably transfected adult mesenchymal bone
      marrow stem cells.
AB  - Increasing attention is being given to the use of adult rather than embryonic
      stem cells, both for research and for the development of transplantation
      treatments for human disease. In particular, mesenchymal bone marrow stem cells
      have been studied extensively because of their ability to self-renew and to give
      rise to various differentiated cell types, and because of the relative ease with
      which they can be obtained and cultured. In addition, the possibility of
      labelling stem cells with green fluorescent protein before transplantation has
      opened new and promising perspectives for their use in basic research. Because no
      structural or ultrastructural description of adult mesenchymal stem cells is
      available in the literature, this paper describes their morphology as revealed by
      light, confocal and electron microscopy, focusing on cells that are particularly
      suitable for transplantation studies, i.e. those derived from rat bone marrow
      transfected with green fluorescent protein. The results provide a basis for
      experimental studies of the differentiation of these cells in normal and
      pathological tissues.

PMID- 16420376
TI  - Three-dimensional study of pelvic asymmetry on anatomical specimens and its
      clinical perspectives.
AB  - The aim of this study was to assess pelvic asymmetry (i.e. to determine whether
      the right iliac bone and the right part of the sacrum are mirror images of the
      left), both quantitatively and qualitatively, using three-dimensional
      measurements. Pelvic symmetry was described osteologically using a common
      reference coordinate system for a large sample of pelvises. Landmarks were
      established on 12 anatomical specimens with an electromagnetic Fastrak system.
      Seventy-one paired variables were tested with a paired t-test and a non
      parametric test (Wilcoxon). A Pearson correlation matrix between the right and
      left values of the same variable was applied exclusively to values that were
      significantly asymmetric in order to calculate a dimensionless asymmetry index,
      ABGi, for each variable. Fifteen variables were significantly asymmetric and
      correlated with the right vs. left sides for the following anatomical regions:
      sacrum, iliac blades, iliac width, acetabulum and the superior lunate surface of
      the acetabulum. ABGi values above a threshold of +/- 4.8% were considered
      significantly asymmetric in seven variables of the pelvic area. Total asymmetry
      involving the right and the left pelvis seems to follow a spiral path in the
      pelvis; in the upper part, the iliac blades rotate clockwise, and in the lower
      part, the pubic symphysis rotates anticlockwise. Thus, pelvic asymmetry may be
      evaluated in clinical examinations by measuring iliac crest orientation.

PMID- 16420375
TI  - Calcium phosphate microcrystal deposition in the human intervertebral disc.
AB  - A variety of crystals have been identified in both normal and pathological
      connective tissues. Calcium phosphate 'cuboidal' microcrystal deposition has been
      found, using transmission electron microscopy (TEM), in femoral articular
      cartilage, where they are distributed as a band 5-50 microm beneath the articular
      surface. These cuboid microcrystals have been identified as magnesium
      whitlockite. Our objective was to investigate their presence in the human
      intervertebral disc. In this study, two degenerate and 15 scoliotic discs were
      examined using light microscopy and TEM techniques to determine the presence of
      calcium phosphate crystals. Calcium pyrophosphate dihydrate (CPPD) deposition was
      identified in one degenerate disc specimen. Using TEM and electron probe
      analysis, cuboid microcrystals were identified in the annulus fibrosus and
      nucleus pulposus of both degenerate specimens, but not in the discs from young
      scoliotic patients. Cuboid microcrystal deposition was found predominantly around
      cells, which were mainly necrotic, with some association with extracellular
      lipidic/membranous debris. This is the first TEM report of whitlockite in the
      intervertebral disc. In one specimen coexistence of cuboid and CPPD crystal
      deposition was found.

PMID- 16420377
TI  - Geometric morphometrics of the shoulder girdle in extant turtles (Chelonii).
AB  - The aim of this study was to identify shape patterns of the shoulder girdle in
      relation to different functional and environmental behaviours in turtles. The
      Procrustes method was used to compare the shoulder girdles (scapula and coracoid)
      of 88 adult extant turtles. The results indicate that four shape patterns can be
      distinguished. The shoulder girdles of (1) terrestrial (Testudinidae), (2) highly
      aquatic freshwater (Trionychidae, Carettochelyidae) and (3) marine turtles
      (Cheloniidae, Dermochelyidae) correspond to three specialized morphological
      patterns, whereas the shoulder girdle of (4) semi-aquatic freshwater turtles
      (Bataguridae, Chelidae, Chelydridae, Emydidae, Kinosternidae, Pelomedusidae,
      Platysternidae, Podocnemididae) is more generalized. In terrestrial turtles, the
      long scapular prong and the short coracoid are associated with a domed shell and
      a mode of locomotion in which walking is predominant. By contrast, highly aquatic
      freshwater turtles share traits with marine turtles. In both, the short scapular
      prong and the long coracoid are associated with a flat shell, and swimming
      locomotion. The enlarged attachment sites of the biceps, coracobrachialis magnus,
      and supracoracoideus also give these strong swimmers a mechanical advantage
      during adduction and retraction of the arm. Increasing size leads to allometrical
      shape changes that emphasize mechanical efficiency both in terrestrial and in
      aquatic turtles.

PMID- 16420379
TI  - The elephant knee joint: morphological and biomechanical considerations.
AB  - Elephant limbs display unique morphological features which are related mainly to
      supporting the enormous body weight of the animal. In elephants, the knee joint
      plays important roles in weight bearing and locomotion, but anatomical data are
      sparse and lacking in functional analyses. In addition, the knee joint is
      affected frequently by arthrosis. Here we examined structures of the knee joint
      by means of standard anatomical techniques in eight African (Loxodonta africana)
      and three Asian elephants (Elephas maximus). Furthermore, we performed
      radiography in five African and two Asian elephants and magnetic resonance
      imaging (MRI) in one African elephant. Macerated bones of 11 individuals (four
      African, seven Asian elephants) were measured with a pair of callipers to give
      standardized measurements of the articular parts. In one Asian and three African
      elephants, kinematic and functional analyses were carried out using a digitizer
      and according to the helical axis concept. Some peculiarities of healthy and
      arthrotic knee joints of elephants were compared with human knees. In contrast to
      those of other quadruped mammals, the knee joint of elephants displays an
      extended resting position. The femorotibial joint of elephants shows a high grade
      of congruency and the menisci are extremely narrow and thin. The four-bar
      mechanism of the cruciate ligaments exists also in the elephant. The main motion
      of the knee joint is extension-flexion with a range of motion of 142 degrees . In
      elephants, arthrotic alterations of the knee joint can lead to injury or loss of
      the cranial (anterior) cruciate ligament.

PMID- 16420378
TI  - Regional variations in human patellar trabecular architecture and the structure
      of the proximal patellar tendon enthesis.
AB  - Proximal patellar tendinopathy occurs as an overuse injury in sport and is also
      characteristic of ankylosing spondylitis patients. It particularly affects the
      posteromedial part of the patellar tendon enthesis, although the reason for this
      is unclear. We investigated whether there are regional differences in the
      trabecular architecture of the patella or in the histology of the patellar tendon
      enthesis that could suggest unequal force transmission from bone to tendon.
      Trabecular architecture was analysed from X-rays taken with a Faxitron
      radiography system of the patellae of dissecting room cadavers and in magnetic
      resonance images of the knees of living volunteers. Structural and fractal
      analyses were performed on the Faxitron digital images using MatLab software.
      Regional differences at the enthesis in the thickness of the uncalcified
      fibrocartilage and the subchondral plate were evaluated histologically in
      cadaveric material. The radiological studies showed that the quantity of bone and
      the apparent trabecular thickness in the patella were greatest medially, and that
      in the lateral part of the patella there were fewer trabeculae which were
      orientated either antero-posteriorly or superiorly inferiorly. The histological
      study showed that the uncalcified fibrocartilage was most prominent medially and
      that the subchondral plate was thinner laterally. Overall, the results indicate
      that mechanical stress at the proximal patellar tendon enthesis is asymmetrically
      distributed and greater on the medial than on the lateral side. Thus, we suggest
      that the functional anatomy of the knee is closely related to regional variations
      in force transmission, which in turn relates to the posteromedial site of
      pathology in proximal patellar tendinopathy.

PMID- 16420380
TI  - Cortical bone development under the growth plate is regulated by mechanical load
      transfer.
AB  - Longitudinal growth of long bones takes place at the growth plates. The growth
      plate produces new bone trabeculae, which are later resorbed or merged into the
      cortical shell. This process implies transition of trabecular metaphyseal
      sections into diaphyseal sections. We hypothesize that the development of
      cortical bone is governed by mechanical stimuli. We also hypothesize that
      trabecular and cortical bone share the same regulatory mechanisms for adaptation
      to mechanical loads. To test these hypotheses, we monitored the development of
      the tibial cortex in growing pigs, using micro-computer tomography and histology.
      We then tested the concept that regulatory mechanisms for trabecular bone
      adaptation can also explain cortical bone development using our mechanical
      stimulation theory, which could explain trabecular bone (re)modelling. The main
      results showed that, from the growth plate towards the diaphysis, the pores of
      the trabecular structure were gradually filled in with bone, which resulted in
      increased density and cortical bone. The computer model largely predicted this
      morphological development. We conclude that merging of metaphyseal trabeculae
      into cortex is likely to be governed by mechanical stimuli. Furthermore, cortex
      development of growing long bones can be explained as a form of trabecular bone
      adaptation, without the need for different regulatory mechanisms for cortical and
      trabecular bone.

PMID- 16420381
TI  - Osteonal crack barriers in ovine compact bone.
AB  - Bone is an anisotropic structure which can be compared to a composite material.
      Discontinuities within its microstructure may provide stress concentration sites
      for crack initiation, but act as a barrier to its propagation. This study looks
      specifically at the relationship between crack length and propagation in compact
      bone. Beam-shaped bone samples from sheep radii were prepared and stained with
      fluorochrome dyes and tested in cyclic fatigue under four-point bending in an
      INSTRON 1341 servo-hydraulic fatigue-testing machine. Samples were tested at a
      frequency of 30 Hz and stress range of 100 MPa under load control. Specimens were
      sectioned transversely using a diamond saw, slides prepared and examined using
      epifluorescence microscopy. Cracks in transverse sections were classified in
      terms of their location relative to cement lines surrounding secondary osteons.
      Mean crack length, crack numerical density and crack surface density were
      examined. Short microcracks (100 microm or less) were stopped at the cement lines
      surrounding osteons, microcracks of intermediate length (100-300 microm) were
      deflected as they hit the cement line, and microcracks that were able to
      penetrate through cement lines were longer (> 400 microm). These data show that
      bone microstructure allows the initiation of microcracks but acts as a barrier to
      crack propagation.

PMID- 16420382
TI  - The functional anatomy of Kager's fat pad in relation to retrocalcaneal problems
      and other hindfoot disorders.
AB  - Kager's fat pad is a mass of adipose tissue occupying Kager's triangle. By means
      of a combined magnetic resonance imaging, ultrasound, gross anatomical and
      histological study, we show that it has three regions that are closely related to
      the sides of the triangle. Thus, it has parts related to the Achilles and flexor
      hallucis longus (FHL) tendons and a wedge of fat adjacent to the calcaneus. The
      calcaneal wedge moves into the bursa during plantarflexion, as a consequence of
      both an upward displacement of the calcaneus relative to the wedge and a downward
      displacement of the wedge relative to the calcaneus. During dorsiflexion, the
      bursal wedge is retracted. The movements are promoted by the tapering shape of
      the bursal wedge and by its deep synovial infolds. Fibrous connections linking
      the fat to the Achilles tendon anchor and stabilize it proximally and thus
      contribute to the motility of its tip. We conclude that the three regions of
      Kager's fat pad have specialized functions: an FHL part which contributes to
      moving the bursal wedge during plantarflexion, an Achilles part which protects
      blood vessels entering this tendon, and a bursal wedge which we suggest minimizes
      pressure changes in the bursa. All three regions contribute to reducing the risk
      of tendon kinking and each may be implicated in heel pain syndromes.

PMID- 16420383
TI  - Experimental determination of the periodicity of incremental features in enamel.
AB  - Vital labelling of hard tissues was used to examine the periodicity of features
      of dental enamel microstructure. Fluorescent labels were administered pre- and
      postnatally to developing macaques (Macaca nemestrina), which were identified
      histologically in dentine and related to accentuated lines in enamel, allowing
      for counts of features within known-period intervals. This study demonstrates
      that cross-striations represent a daily rhythm in enamel secretion, and suggests
      that intradian lines are the result of a similar 12-h rhythm. Retzius lines were
      found to have a regular periodicity within individual dentitions, and laminations
      appear to represent a daily rhythm that also shows 12-h subdivisions. The
      inclusion of intradian lines and laminations represents the first empirical
      evidence for their periodicities in primates; these features frequently
      complicate precise measurements of secretion rate and Retzius line periodicity,
      which are necessary for determination of crown formation time. The biological
      basis of incremental feature formation is not completely understood; long-period
      features may result from interactions between short-period rhythms, although this
      does not explain the known range of Retzius line periodicities within humans or
      among primates. Studies of the genetic, neurological and hormonal basis of
      incremental feature formation are needed to provide more insight into their
      physiological and structural basis.

PMID- 16420384
TI  - Multiple-image radiography for human soft tissue.
AB  - Conventional radiography only provides a measure of the X-ray attenuation caused
      by an object; thus, it is insensitive to other inherent informative effects, such
      as refraction. Furthermore, conventional radiographs are degraded by X-ray
      scatter that can obscure important details of the object being imaged. The novel
      X-ray technology diffraction-enhanced imaging (DEI) has recently allowed the
      visualization of nearly scatter-free images displaying both attenuation and
      refraction properties. A new method termed multiple-image radiography (MIR) is a
      significant improvement over DEI, corrects errors in DEI, is more robust to noise
      and produces an additional image that is entirely new to medical imaging. This
      new image, which portrays ultra-small-angle X-ray scattering (USAXS) conveys the
      presence of microstructure in the object, thus differentiating homogeneous
      tissues from tissues that are irregular on a scale of micrometres. The aim of
      this study was to examine the use of MIR for evaluation of soft tissue, and in
      particular to conduct a preliminary investigation of the USAXS image, which has
      not previously been used in tissue imaging.

PMID- 16420385
TI  - The accuracy of histological assessments of dental development and age at death.
AB  - Histological analyses of dental development have been conducted for several
      decades despite few studies assessing the accuracy of such methods. Using known
      period incremental features, the crown formation time and age at death of five
      pig-tailed macaques (Macaca nemestrina) were estimated with standard histological
      techniques and compared with known ages. Estimates of age at death ranged from
      8.6% underestimations to 15.0% overestimations, with an average 3.5% overestimate
      and a 7.2% average absolute difference. Several sources of error were identified
      relating to preparation quality and section obliquity. These results demonstrate
      that histological analyses of dental development involving counts and
      measurements of short- and long-period incremental features may yield accurate
      estimates, particularly in well-prepared material. Values from oblique sections
      (or most naturally fractured teeth) should be regarded with caution, as obliquity
      leads to inflated cuspal enamel formation time and underestimated imbricational
      formation time. Additionally, Shellis's formula for extension rate and crown
      formation time estimation was tested, which significantly overestimated crown
      formation time due to underestimated extension rate. It is suggested that
      Shellis' method should not be applied to teeth with short, rapid periods of
      development, and further study is necessary to validate this application in other
      material.

PMID- 16420387
TI  - EFNS guidelines on management of neurological problems in liver transplantation.
AB  - Neurological impairment after orthotopic liver transplantation (OLT) is common
      and represents a major source of morbidity and mortality. The diagnosis and
      management of neurological problems occurring after OLT are difficult and
      evidence-based guidelines for this task are currently lacking. A Task Force was
      set up under the auspices of the European Federation of Neurological Societies to
      devise guidelines to prevent and manage neurological problems in OLT. We selected
      six major neurological problems and approached them combining an evidence-based
      scientific literature analysis with a search of consensus by means of a Delphi
      process. Search results were translated into a series of recommendations
      constituting a basis for better care of patients with neurological complications
      after OLT.

PMID- 16420388
TI  - Relationship of deep white matter hyperintensities and cerebral blood flow in
      severe carotid artery stenosis.
AB  - Leukoaraiosis (LA) has been associated with abnormalities of both large and small
      blood vessels. This study attempts to clarify the pathogenesis of LA by testing
      the hypothesis that increased frequency of LA with occlusive extra-cranial
      arterial disease results directly from global reduction in cerebral blood flow
      (CBF). Thirty-five normal subjects and 55 patients with carotid stenosis (>70%)
      were studied using MR. CBF was measured using phase contrast MR angiography and
      LA was scored using previously validated scoring system. Patients were divided
      into those with evidence of previous infarction on MRI and those without. LA was
      more severe in patients than in normal subjects (P<0.01) and correlated with age
      in normal subjects but not in patients. CBF in patients with (809+/-214 ml/min)
      and without infarction (mean 792+/-181 ml/min) was significantly lower than in
      normal subjects (mean 1073+/-194 ml/min). There was no correlation between the
      severity of LA and measured CBF in any group. The severity of LA is greater in
      patients with severe carotid stenosis but is not correlated to reductions in CBF.
      This suggests that microvascular abnormality is the dominant pathogenetic factor
      in LA even in the presence of severe stenotic/occlusive large vessel disease.

PMID- 16420389
TI  - Functional decline in frail community-dwelling stroke patients.
AB  - Patients who suffer a stroke event are at high risk of functional decline after
      the post-acute rehabilitation period. The aim of the present study was the
      evaluation of factors associated with functional decline in a large sample of
      older patients with stroke living in the community. The study population
      consisted of all patients admitted to home care programs after a post-acute
      rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian
      Home Health Agencies from 2000 to 2002 (n=1338). For the present study we
      selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home
      care program, 149 out of 355 stroke survivors (42%) had presented a worsening in
      the activities of daily living (ADL) scale score. In the final adjusted model,
      patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer
      (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29),
      or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to
      significantly decline in physical functioning after a period of 1 year in-home
      care program. Our study documents that functional decline of stroke patients was
      largely dependent on specific subjects' clinical characteristics. Three of four
      concomitant disabling conditions associated in our sample with functional decline
      -pressure ulcer, urinary incontinence, hearing--can be prevented and eventually
      treated or modified. Appropriate post-acute rehabilitation programs and adequate
      home care interventions focused on the prevention and treatment of these
      conditions might be correlated to better outcomes in older post-stroke patients.

PMID- 16420390
TI  - Cerebral blood flow velocity changes during meaningful and meaningless gestures-
      a functional transcranial Doppler study.
AB  - The aim of the study was to use functional transcranial Doppler to investigate
      the possibility of revealing different activation patterns during healthy
      subjects' performance of meaningful and meaningless actions. Mean flow velocity
      (MFV) changes were recorded in middle cerebral arteries (MCAs) of 26 normal
      subjects during a rest phase and during performance of meaningful and meaningless
      actions. The meaningful task consisted of pouring sugar into a cup with a
      teaspoon. The meaningless action was an arm movement similar to that necessary
      for pouring sugar in a cup but without any tool and thus without a goal.
      Performing actions with or without meaning was associated with different patterns
      of MFV changes, as documented by the triple interaction condition x performing
      arm x side of recording [F(1, 25)=10.977; P=0.003]. During the meaningful action,
      MFV in MCAs increased significantly more than during the meaningless action.
      During the meaningless action, the MFV increase was significantly higher in the
      contralateral than in the ipsilateral MCA to the arm performing the task and the
      meaningful action determined a bilateral MFV increase only when the task was
      performed with the left arm. When the same task was performed with the right arm,
      the MFV increase was significantly higher in the contralateral than in the
      ipsilateral MCA. These findings suggest that the content of an action can
      influence MFV changes and further confirm the usefulness of transcranial Doppler
      in neuropsychological investigation.

PMID- 16420392
TI  - A 24-week, double-blind, placebo-controlled study of three dosages of
      Cerebrolysin in patients with mild to moderate Alzheimer's disease.
AB  - Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be
      effective in Alzheimer's disease in earlier trials. The efficacy and safety of
      three dosages of Cere were investigated in this randomized, double-blind, placebo
      controlled, study. Two hundred and seventy-nine patients were enrolled (69 Cere
      10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv
      infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and
      thereafter, two iv infusions per week for 8 weeks. Effects on cognition and
      clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning
      of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment
      Scale (ADAS)-cog. At week 24, significant improvement of cognitive performance on
      the ADAS-cog (P=0.038) and global function (CIBIC+; P>0.001) was observed for the
      10 ml dose. The 30 and 60 ml doses showed significant improvement of the global
      outcome but failed to show significant improvement of cognition. The results are
      consistent with a reversed U-shaped dose-response relationship for Cere. The
      percentage of patients reporting adverse events was similar across all study
      groups. Cere treatment was well tolerated and led to significant, dose-dependent
      improvement of cognition and global clinical impression.

PMID- 16420393
TI  - Influence of melatonin on fatigue severity in patients with chronic fatigue
      syndrome and late melatonin secretion.
AB  - The effect of melatonin, a chronobiotic drug, was explored in 29 patients with
      chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than
      21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg
      of melatonin orally, 5 h before DLMO during 3 months. Their responses to the
      checklist individual strength (CIS), a reliable questionnaire measuring the
      severity of personally experienced fatigue, were assessed twice with a 6-week
      interval immediately before the treatment and once after 3 months treatment. In
      the pre-treatment period the fatigue sub-score improved significantly. After
      treatment, the total CIS score and the sub-scores for fatigue, concentration,
      motivation and activity improved significantly. The sub-score fatigue normalized
      in two of the 29 patients in the pre-treatment period and in eight of 27 patients
      during treatment. This change was significant. In the patients with DLMO later
      than 22.00 hours (n=21) the total CIS score and the sub-scores for fatigue,
      concentration and activity improved significantly more than in the patients (n=8)
      with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for
      patients with CFS and late DLMO, especially in those with DLMO later than 22.00
      hours.

PMID- 16420391
TI  - Tryptophan metabolism and oxidative stress in patients with chronic brain injury.
AB  - The kynurenine pathway generates the excitotoxic N-methyl-d-aspartate receptor
      agonist, quinolinic acid and the glutamate antagonist, kynurenic acid, as well as
      free-radical generators. We investigated the status of the pathway following
      severe brain injury sustained at least 1 year previously in 15 patients compared
      with controls. At baseline, patients with brain injury showed increased levels of
      neopterin, erythrocyte sedimentation rate, C-reactive protein and peroxidation
      products in the blood compared with controls, indicating persistent inflammation
      and oxidative stress. At baseline and following tryptophan depletion, more
      tryptophan was converted to kynurenine in patients than controls, but less
      kynurenine was converted into the neuroprotectant, kynurenic acid. This suggests
      that neuroprotection by kynurenic acid may be inadequate in brain-damaged
      patients even many years after injury. On tryptophan loading, patients
      metabolized more kynurenine into kynurenic acid than controls, a process which
      may be neuroprotective. In addition, lower levels of 3-hydroxykynurenine and 3
      hydroxyanthranilic acid in patients after tryptophan loading should be protective
      since these compounds generate free radicals. The results suggest that for brain
      damaged patients, increased activation of the kynurenine pathway, oxidative
      stress and raised levels of inflammation continue many years after the original
      insult, possibly contributing to the continuing cerebral dysfunction in these
      patients.

PMID- 16420394
TI  - A recommended treatment algorithm in relapsing multiple sclerosis: report of an
      international consensus meeting.
AB  - An International Working Group for Treatment Optimization in MS met to recommend
      evidence-based therapeutic options for the management of suboptimal responses or
      intolerable side-effects in patients treated with disease-modifying drugs (DMDs)
      for multiple sclerosis (MS). Several DMDs are now available for the treatment of
      MS that have been shown to alter the clinical course of the disease by decreasing
      disease activity and delaying the progression of disability. Nevertheless, many
      patients continue to experience disease activity whilst on treatment, and
      recommendations have been made on how the success of therapy in an individual
      patient can be assessed. However, even after having identified criteria for a
      suboptimal response to current treatments, clinicians require guidance on how to
      improve the outcomes. This report summarizes the conclusions from a workshop at
      which this issue was addressed. We suggest treatment pathways for optimizing
      therapy for those patients with suboptimal responses to DMDs, and therapeutic
      options for patients with unacceptable side-effects on their current therapy.

PMID- 16420395
TI  - Repeat intrathecal triamcinolone acetonide application is beneficial in
      progressive MS patients.
AB  - Available immunomodulatory and conventional steroid treatment regimens provide a
      limited symptomatic benefit for patients with progressive multiple sclerosis
      (MS). We performed an open trial on the short-term efficacy of repeated
      intrathecal application of the sustained release steroid triamcinolone acetonide
      (TCA) in 27 progressive MS patients. Six TCA administrations, performed every
      third day, reduced the Expanded Disability Status Scale (EDSS) score [initial:
      5.4+/-1.3, 3-7.5 (mean+/-SD, range); end: 4.9+/-1.1; 2.5-6.5; P<0.001] and
      significantly increased the walking distance and speed in particular after the
      fourth TCA injection. Concomitantly serially determined cerebrospinal fluid (CSF)
      markers of cell injury, neuron-specific enolase, total tau-protein, S-100, and
      beta-amyloid did not significantly change within the interval of TCA treatment.
      No serious side effects appeared. We conclude that repeat intrathecal injection
      of 40 mg TCA provides a substantial benefit in progressive MS patients with
      predominant spinal symptoms and does not alter CSF markers of neuronal cell
      injury.

PMID- 16420396
TI  - A 9-year review of dystonia from a movement disorders clinic in Singapore.
AB  - The clinical features of dystonia have not been evaluated in Southeast Asia. We
      therefore investigated the clinical spectrum and characteristics of dystonia in
      Singapore, a multi-ethnic Southeast Asian country comprising 77% Chinese, 14%
      Malays, and 8% Indians. We identified all dystonia patients from the Movement
      Disorders database and Botulinum Toxin clinic between 1995 and November 2004.
      Their medical records were reviewed to verify the diagnosis of dystonia and
      obtain demographic and clinical data using a standardized data collection form. A
      total of 119 (73%) patients had primary dystonia whilst 45 (27%) had secondary
      dystonia. There were 77% Chinese, 9% Malays, and 8% Indians. The most common
      focal dystonia were cervical dystonia (47%), writer's cramp (32%), and
      blepharospasm (11%). There was no significant difference in the distribution of
      dystonia between the different races. Males were noted to have earlier onset of
      dystonia overall. There was a significant male predominance in primary dystonia
      overall (M:F 1.6:1, P=0.008) and in the subgroup of focal dystonia (M:F 1.6:1,
      P=0.037). This contrasts with previous studies that found a female predominance.
      The role of genetic, hormonal, and environmental factors and their interactions
      need to be investigated to better understand the gender differences in the
      occurrence of dystonia.

PMID- 16420397
TI  - The corticobasal syndrome triggered by central pontine myelinolysis.
AB  - Single case reports have described movement disorders including parkinsonism,
      dystonia and chorea, but not corticobasal syndrome as a consequence of central
      pontine and extrapontine myelinolysis. We report a case of a 61-year-old woman
      who developed progressive asymmetric parkinsonism with ideomotor apraxia and
      cortical sensory deficits following central pontine myelinolysis.

PMID- 16420398
TI  - Adult abdominal migraine: a new syndrome or sporadic feature of migraine
      headache? A case report.
AB  - Abdominal migraine is one of the variants of migraine headache typically
      occurring in children and coded as 1.3.2 in the revised edition of IHS
      classification within the group 'Childhood periodic syndromes that are commonly
      precursors of migraine'. The affected children frequently develop typical
      migraine later in their life. We report a case of a 23 years old woman affected
      by attacks of recurrent abdominal pain accompanied by migraine. Abdominal pain
      attacks started in the adolescence and persisted without headache until the
      patient was 21. At this time, she experienced migraine pain accompanied by
      nausea, photophobia and phonophobia and associated to acute abdominal pain.
      Neuroimaging investigations and laboratory testing excluded any underlying
      organic disease. Complete remission of abdominal attacks was obtained during 4
      month treatment period with pizotifen. Attacks fulfil IHS diagnostic criteria for
      'abdominal migraine', although of late onset. This case report suggests that
      'abdominal migraine' is a migraineous disorder to be hypothesized in adult
      patients after having disclosed any organic disease. As reported in the
      literature, 'adult abdominal migraine' is a sporadic migraine subtype in adult
      patients and it is not to be considered as a new migraineous syndrome.

PMID- 16420399
TI  - Aging and oxidative stress in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disorder, which may
      possibly be induced by oxidative stress. However, the age-related alteration of
      the endogenous antioxidant system is not well understood. To better understand
      this, we measured Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx),
      and 4-hydroxynonenal (HNE)-conjugated GPx in cerebrospinal fluid of PSP patients
      by enzyme linked immunosorbent assay. A significant increase in the Cu/Zn-SOD
      level was detected in PSP group compared with controls. The levels of Cu/Zn-SOD
      and GPx in PSP group showed positive correlations with age. Two-thirds of total
      GPx was present as the HNE-conjugated form with positive correlation in PSP
      group. In conclusion, the endogenous antioxidant system of PSP patients appears
      to be activated with aging, however, it might be unable to function effectively
      because of conjugation with HNE.

PMID- 16420400
TI  - Listeria rhombencephalitis--a case report.

PMID- 16420401
TI  - A quadruple spontaneous dissection of cervicocerebral arteries.

PMID- 16420402
TI  - Anti-GM1 antibody-negative acute motor axonal neuropathy after Mycoplasma
      pneumoniae infection.

PMID- 16420403
TI  - The effect of ischemic cerebrovascular disease on the clinical characteristics of
      Parkinson's disease. A post-mortem study.

PMID- 16420404
TI  - Postpartum activation of multiple sclerosis: MRI imaging and immunological
      characterization of a case.

PMID- 16420405
TI  - Sural nerve and epidermal vascular abnormalities in a case of POEMS syndrome.

PMID- 16420410
TI  - Role of gap junctional coupling in astrocytic networks in the determination of
      global ischaemia-induced oxidative stress and hippocampal damage.
AB  - While there is evidence that gap junctions play important roles in the
      determination of cell injuries, there is not much known about mechanisms by which
      gap junctional communication may exert these functions. Using a global model of
      transient ischaemia in rats, we found that pretreatment with the gap junctional
      blockers carbenoxolone, 18alpha-glycyrrhetinic acid and endothelin, applied via
      cannulae implanted into the hippocampus in one hemisphere, resulted in decreased
      numbers of TUNEL-positive neurons, as compared with the contralateral hippocampus
      that received saline injection. Post-treatment with carbenoxolone for up to 30
      min after the stroke injury still resulted in decreased cell death, but post
      treatment at 90 min after the ischaemic insult did not result in differences in
      cell death. However, quinine, an inhibitor of Cx36-mediated gap junctional
      coupling, did not result in appreciable neuroprotection. Searching for a possible
      mechanism for the observed protective effects, possible actions of the gap
      junctional blockers in the electrical activity of the hippocampus during the
      ischaemic insult were assessed using intracerebral recordings, with no
      differences observed between the saline-injected and the contralateral drug
      injected hippocampus. However, a significant reduction in lipid peroxides, a
      measure of free radical formation, in the hippocampus treated with carbenoxolone,
      revealed that the actions of gap junctional coupling during injuries may be
      causally related to oxidative stress. These observations suggest that coupling in
      glial networks may be functionally important in determining neuronal
      vulnerability to oxidative injuries.

PMID- 16420411
TI  - Striatal modulation of cAMP-response-element-binding protein (CREB) after
      excitotoxic lesions: implications with neuronal vulnerability in Huntington's
      disease.
AB  - Recent evidence has shown that the activity of cAMP responsive element-binding
      protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's
      disease (HD) [Steffan et al. (2000)Proc. Natl Acad. Sci. USA, 97, 6763-6768;
      Gines et al. (2003)Hum. Mol. Genet., 12, 497-508; Rouaux et al. (2004) Biochem.
      Pharmacol., 68, 1157-1164; Sugars et al. (2004)J. Biol. Chem., 279, 4988-4999].
      Such decrease is thought to reflect the impaired energy metabolism observed in a
      HD mouse model, where a decline in striatum cAMP levels has been observed [Gines
      et al. (2003)Hum. Mol. Genet., 12, 497-508]. Increased levels of CREB have also
      been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002)Neuron,
      35, 605-623; Lonze et al. (2002)Neuron, 34, 371-385]. Our study aimed to
      investigate the distribution of CREB in the neuronal subpopulations of the
      striatum in normal rats compared to the HD model of quinolinic acid lesion.
      Twenty-five Wistar rats were administered quinolinic acid 100 mm into the right
      striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks,
      respectively. The contralateral striata were used as controls. Dual-label
      immunofluorescence was employed using antibodies against phosphorylated CREB and
      each of the different neuronal subpopulations markers. Our results show that
      activated CREB levels decrease progressively in projection neurons and
      parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain
      stable in cholinergic and somatostatin interneurons. Thus, we speculate that the
      ability of cholinergic interneurons to maintain their levels of CREB after
      excitotoxic lesions is one of the factors determining their protection in
      Huntington's disease.

PMID- 16420412
TI  - Inhibition of vascular endothelial growth factor receptor 2 activity in
      experimental brain contusions aggravates injury outcome and leads to early
      increased neuronal and glial degeneration.
AB  - Angiogenesis following traumatic brain injuries (TBIs) may be of importance for
      post-traumatic reparative processes and the development of secondary injuries. We
      have previously shown expression of vascular endothelial growth factor (VEGF), a
      major regulator of endothelial cell proliferation, angiogenesis and vascular
      permeability, and VEGF receptors (VEGFR1 and 2) after TBI in rat. In the present
      work we tried to further elucidate the role of VEGF after TBI by performing
      specific VEGFR2 activity inhibition. In rats subjected to VEGFR2 blockage we
      report an increased haemorrhagic area (P < 0.05), early increase in serum levels
      of neural injury marker neuron-specific enolase (P < 0.05) and glial injury
      marker S100beta (P < 0.05), and increased numbers of terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin nick end labelling- (TUNEL
      ) and FluoroJade B- (P < 0.05) positive cells, all increases preceding the known
      VEGF/VEGFR vascular response in brain trauma. An increase in lesion area, as
      measured by decreased microtubuli-associated protein 2 expression (P < 0.05) and
      increased glial fibrillary acidic protein reactivity (P < 0.05), could also be
      demonstrated. In addition, vascular density, as measured by von Willebrandt
      factor-positive cells, was decreased (P < 0.05). No differences in post-traumatic
      inflammatory response, as measured by stainings for macrophages, granulocytes and
      intracellular adhesion molecules, were shown between the groups. Taken together,
      our findings point towards VEGF/VEGFR2 up-regulation after TBI as being an
      important endogenous cytoprotective mechanism in TBI. The possible importance of
      VEGF on the vascular, neuronal and glial compartments of the neurovascular unit
      after TBI is discussed.

PMID- 16420413
TI  - 1-hydroxyPGE reduces infarction volume in mouse transient cerebral ischemia.
AB  - Differential neurological outcomes due to prostaglandin E2 activating G-protein
      coupled prostaglandin E (EP) receptors have been observed. Here, we investigated
      the action of the EP4/EP3 agonist 1-hydroxyPGE1 (1-OHPGE1) in modulating
      transient ischemic brain damage. C57BL/6 mice were pretreated 50 min before
      transient occlusion of the middle cerebral artery with an intraventricular
      injection of 1-OHPGE1 (0.1, 0.2, 2.0 nmol/0.2 microL). Brain damage 4 days after
      reperfusion, as estimated by infarct volume, was significantly reduced by more
      than 19% with 1-OHPGE1 in the two higher-dose groups (P < 0.05). To further
      address whether protection also was extended to neurons, primary mouse cultured
      neuronal cells were exposed to N-methyl-D-aspartate. Co-treatment with 1-OHPGE1
      resulted in significant neuroprotection (P < 0.05). To better understand
      potential mechanisms of action and to test whether changes in cyclic adenosine
      monophosphate (cAMP) levels and downstream signaling would be neuroprotective, we
      measured cAMP levels in primary neuronal cells. Brief exposure to 1-OHPGE1
      increased cAMP levels more than twofold and increased the phosphorylation of
      extracellular-regulated kinases at positions Thr-202/Tyr-204. In a separate
      cohort of animals, 1-OHPGE1 at all doses tested produced no significant effect on
      the physiological parameters of core body temperature, mean arterial pressure and
      relative cerebral blood flow observed following drug treatment. Together, these
      results suggest that modulation of PGE2 receptors that increase cAMP levels and
      activate extracellular-regulated kinases 1/2 caused by treatment with 1-OHPGE1
      can be protective against neuronal injury induced by focal ischemia.

PMID- 16420414
TI  - Anti-apoptotic effects of allopregnanolone on P19 neurons.
AB  - Progesterone and its metabolites are potent allosteric modulators of GABA(A)
      receptor function, through a direct, non-genomic interaction with specific
      receptor subtypes. In addition, fluctuations in the concentration of
      progesterone, and allopregnanolone in particular, have been shown to modulate
      GABA(A) receptor gene expression and activity. In this study, mouse P19 cells
      were induced to differentiate into post-mitotic neurons which express specific
      neuronal markers, including GABA(A) and N-methyl-d-aspartate (NMDA) receptors.
      Apoptotic cell death, induced in the presence of NMDA, was efficiently prevented
      by allopregnanolone and dehydroepiandrosterone (DHEA) but not DHEA sulfate.
      Apoptosis was accompanied by cytochrome c release to the cytoplasm and Bax
      translocation to the mitochondria, while the levels of the anti-apoptotic
      proteins Bcl-2 and Bcl-xL remained unchanged. In the presence of the most potent
      neurosteroid, allopregnanolone, DNA fragmentation as well as cytochrome c and Bax
      translocation were prevented. On the other hand, short-term exposure (1-20
      microm, 24 h) of P19-derived neurons to allopregnanolone and DHEA significantly
      increased the levels of alpha1 and beta2 mRNAs of GABA(A) receptor, while the
      levels of NR1 mRNA of NMDA receptor were not altered. These results suggest that
      neurosteroids, interfering with the mitochondrial apoptotic pathway, are able to
      act as survival factors in neuronal cells, while they contribute to GABA(A)
      receptor plasticity modulating the expression of its subunits.

PMID- 16420415
TI  - Neuroprotective effects of green and black teas and their catechin gallate esters
      against beta-amyloid-induced toxicity.
AB  - Teas represent a large family of plants containing high amounts of polyphenols
      that may confer health benefits in various diseases. Recently, it has been
      hypothesized that tea consumption may also reduce the risk of age-related
      neurodegenerative pathologies. Considering the deleterious role of beta-amyloid
      (Abeta) in the aetiology of Alzheimer's disease (AD), we investigated green and
      black tea extracts and flavan-3-ols (present as monomers and dimers in green and
      black forms, respectively) against toxicity induced by Abeta-derived peptides
      using primary cultures of rat hippocampal cells as model. Both green and black
      tea extracts (5-25 microg/mL) displayed neuroprotective action against Abeta
      toxicity. These effects were shared by gallic acid (1-20 microm), epicatechin
      gallate (ECG; 1-20 microM) and epigallocatechin gallate (EGCG; 1-10 microM), the
      former being the most potent flavan-3-ol. In contrast, epicatechin and
      epigallocatechin were ineffective in the same range of concentrations. Moreover,
      only tea flavan-3-ol gallate esters (i.e. ECG, EGCG) and gallic acid inhibited
      apoptotic events induced by Abeta(25-35). Interestingly, EGCG and gallic acid
      inhibited Abeta aggregation and/or the formation of Abeta-derived diffusible
      neurotoxin ligands. Taken together, these results indicate that the catechin
      gallates (through the galloyl moiety) contribute to the neuroprotective effects
      of both green and black teas. Moreover, the protective effect of EGCG is likely
      to be associated, at least in part, with its inhibitory action on Abeta
      fibrils/oligomers formation. These data also support the hypothesis that not only
      green but also black teas may reduce age-related neurodegenerative diseases, such
      as AD.

PMID- 16420416
TI  - Gene expression pathways induced by axotomy and decentralization of rat superior
      cervical ganglion neurons.
AB  - To identify genes potentially involved in remodelling synaptic connections, we
      induced the temporary detachment of pre- and post-synaptic elements by axotomy or
      denervation of rat superior cervical ganglion neurons. cDNA microarray analysis
      followed by stringent selection criteria allowed the identification of a panel of
      genes whose expression was modulated by axotomy at various time points after
      injury. Among these genes, 11 were validated by real-time reverse transcriptase
      polymerase chain reaction on independently prepared samples after superior
      cervical ganglion neuron axotomy (1, 3 and 6 days) and compared with the effect
      of decentralization (8 h, 1 and 3 days). These genes code for extracellular
      matrix/space [apolipoprotein D (apoD), decorin, collagen alpha1 type I, collagen
      alpha1 type III] and intermediate filament (vimentin) proteins, for modulators of
      neurite outgrowth (thrombin receptor, plasminogen activator inhibitor-1, bone
      morphogenetic protein 4, annexin II and S-100-related protein, clone 42C) and for
      a nerve cell transcription factor (brain finger protein). Eight of these 11 genes
      showed significant and persistent modulations after both types of injury.
      Finally, protein levels of apoD were shown to increase in superior cervical
      ganglion after axotomy. Our results identify hitherto unrecorded genes responsive
      to axotomy and decentralization of superior cervical ganglion neurons, and
      probably involved in synapse formation, remodelling and elimination.

PMID- 16420417
TI  - Loss of retinal progenitor cells leads to an increase in the retinal stem cell
      population in vivo.
AB  - Retinal stem cells [with the potential to produce either neural retinal
      progenitors or retinal pigment epithelial (RPE) progenitors] exist in the
      mammalian eye throughout life, and indeed the greatest absolute increase in the
      stem population occurs postnatally. The stem cells proliferate embryonically and
      thus may help to build the retina initially, but in postnatal mammals they
      clearly do not proliferate to regenerate the retina in response to injury. Using
      Chx10(orJ/orJ) and Mitf(mi/mi) mice, with small eye phenotypes due to the
      reduction of the neural retinal progenitor population and the retinal pigmented
      epithelial progenitor population, respectively, we now report that the retinal
      stem cell population, when assayed from the ciliary margin, increases 3-8-fold in
      both mutants. These findings suggest that the mammalian retinal stem cell
      population may be capable of responding to genetically induced signals from the
      progenitor populations.

PMID- 16420418
TI  - Neurogenic niche modulation by activated microglia: transforming growth factor
      beta increases neurogenesis in the adult dentate gyrus.
AB  - Adult neural stem cells (NSC) proliferate and differentiate depending on the
      composition of the cellular and molecular niche in which they are immersed. Until
      recently, microglial cells have been ignored as part of the neurogenic niche. We
      studied the dynamics of NSC proliferation and differentiation in the dentate
      gyrus of the hippocampus (DG) and characterized the changes of the neurogenic
      niche in adrenalectomized animals (ADX). At the cellular level, we found
      increased NSC proliferation and neurogenesis in the ADX animals. In addition, a
      morphologically distinct subpopulation of NSC (Nestin+/GFAP-) with increased
      proliferating profile was detected. Interestingly, the number of microglial cells
      at stages 2 and 3 of activation correlated with increased neurogenesis (r2 =
      0.999) and the number of Nestin-positive cells (r2 = 0.96). At the molecular
      level, transforming growth factor beta (TGF-beta) mRNA levels were increased 10
      fold in ADX animals. Interestingly, TGF-beta levels correlated with the amount of
      neurogenesis detected (r2 = 0.99) and the number of stage 2 and 3 microglial
      cells (r2 = 0.94). Furthermore, blockade of TGF-beta biological activity by
      administration of an anti-TGF-beta type II receptor antibody diminished the
      percentage of 5-bromo-2'-deoxyuridine (BrdU)/PSA-NCAM-positive cells in vivo.
      Moreover, TGF-beta was able to promote neurogenesis in NSC primary cultures. This
      work supports the idea that activated microglial cells are not pro- or anti
      neurogenic per se, but the balance between pro- and anti-inflammatory secreted
      molecules influences the final effect of this activation. Importantly, we
      identified an anti-inflammatory cytokine, TGF-beta, with neurogenic potential in
      the adult brain.

PMID- 16420419
TI  - An identified central pattern-generating neuron co-ordinates sensory-motor
      components of respiratory behavior in Lymnaea.
AB  - Defining the attributes of individual central pattern-generating (CPG) neurons
      underlying various rhythmic behaviors are fundamental to our understanding of how
      the brain controls motor programs, such as respiration and locomotion. To this
      end, we have explored a simple invertebrate preparation in which the neuronal
      basis of respiratory rhythmogenesis can be investigated from the whole animal to
      a single cell level. An identified dopaminergic neuron, termed right pedal dorsal
      1 (RPeD1), is a component of the CPG network which controls hypoxia-driven,
      aerial respiration in the fresh water snail Lymnaea stagnalis. Using intact, semi
      intact and isolated brain preparations, we have discovered that in addition to
      its role as a respiratory CPG neuron, RPeD1 co-ordinates sensory-motor input from
      the pneumostome (the respiratory orifice) at the water/air interface to initiate
      respiratory rhythm generation. An additional, novel role of RPeD1 was also found.
      Specifically, direct intracellular stimulation of RPeD1 induced pneumostome
      openings, in the absence of motor neuronal activity. To determine further the
      role of RPeD1 in the respiratory behavior of intact animals, either its axon was
      severed or the soma selectively killed. Many components of the respiratory
      behavior in the intact animals were found to be perturbed following RPeD1 axotomy
      or 'somatomy' (soma removed). Taken together, the data presented provide a direct
      demonstration that RPeD1 is a multifunctional CPG neuron, which also serves many
      additional roles in the control of breathing behavior, ranging from co-ordination
      of mechanosensory input to the motor control of the respiratory orifice.

PMID- 16420420
TI  - Influence of photoperiodic history on clock genes and the circadian pacemaker in
      the rat retina.
AB  - The influence of seasonal lighting conditions on expression of clock genes and
      the circadian pacemaker was investigated in the rat retina. For this purpose, the
      24-h profiles of nine clock genes (bmal1, clock, per1, per2, per3, dec1, dec2,
      cry1 and cry 2) and the arylalkylamine N-acetyltransferase gene as an indicator
      of the circadian pacemaker output were compared between light-dark periods of 8 :
      16 and 16 : 8 h. The photoperiod influenced the daily patterns of the amount of
      transcript for per1, per3, dec2 and arylalkylamine N-acetyltransferase. This
      indicates that photoperiodic information modulates clock gene expression in
      addition to the circadian pacemaker of the retina. Under constant darkness,
      photoperiod-dependent changes in the daily profile of the level of transcript
      persisted for the arylalkylamine N-acetyltransferase gene but not for any of the
      clock genes. Hence, quantitative expression of each clock gene is influenced by
      the photoperiod only under the acute light-dark cycle, whereas the pacemaker is
      capable of storing photoperiodic information from past cycles.

PMID- 16420422
TI  - ATP activates both receptor and sustentacular supporting cells in the olfactory
      epithelium of Xenopus laevis tadpoles.
AB  - Nucleotides and amino acids are acknowledged categories of water-borne olfactory
      stimuli. In previous studies it has been shown that larvae of Xenopus laevis are
      able to sense amino acids. Here we report on the effect of ATP in the olfactory
      epithelium (OE) of Xenopus laevis tadpoles. First, ATP activates a subpopulation
      of cells in the OE. The ATP-sensitive subset of cells is almost perfectly
      disjoint from the subset of amino acid-activated cells. Both responses are not
      mediated by the well-described cAMP transduction pathway as the two
      subpopulations of cells do not overlap with a third, forskolin-activated
      subpopulation. We further show that, in contrast to amino acids, which act
      exclusively as olfactory stimuli, ATP appears to feature a second role.
      Surprisingly it activated a large number of sustentacular supporting cells (SCs)
      and, to a much lower extent, olfactory receptor neurons. The cells of the amino
      acid- and ATP-responding subsets featured differences in shape, size and position
      in the OE. The latencies to activation upon stimulus application differed
      markedly in these subsets. To obtain these results two technical points were
      important. We used a novel dextran-tetramethylrhodamine-backfilled slice
      preparation of the OE and we found out that an antibody to calnexin, a known
      molecular chaperone, also labels SCs. Our findings thus show a strong effect of
      ATP in the OE and we discuss some of the possible physiological functions of
      nucleotides in the OE.

PMID- 16420421
TI  - A postnatal switch in GABAergic control of spinal cutaneous reflexes.
AB  - GABAergic signalling exerts powerful inhibitory control over spinal tactile and
      nociceptive processing, but during development GABA can be depolarizing and the
      functional consequences of this upon neonatal pain processing is unknown. Here we
      show a postnatal switch in tonic GABA(A) receptor (GABA(A)R) modulation of
      cutaneous tactile and nociceptive reflexes from excitation to inhibition, but
      only in the intact spinal cord. Neonatal and 21-day-old (P21) rats were
      intrathecally treated with one of the GABA(A)R antagonists bicuculline and
      gabazine, with both compounds dose-dependently decreasing hindpaw mechanical and
      thermal withdrawal thresholds in P21 rats but increasing them in P3 neonates.
      Intrathecal gabazine also produced an increase in the cutaneous evoked
      electromyography (EMG) response of the biceps femoris in P21 rates but lowering
      the response in neonates. Injections of 3H-gabazine in the L4-L5 region at P3
      confirmed that gabazine binding was restricted to the lumbar spinal cord.
      Spinalization of P3 neonates at the upper thoracic level prior to drug
      application reversed the behavioural and EMG responses to GABA antagonists so
      that they resembled those of P21 rats. The effects of spinalization were
      consistent with gabazine facilitation of ventral root potentials observed in
      isolated neonatal spinal cord. These data show a marked postnatal developmental
      switch in GABAergic control of neonatal nociception that is mediated by
      supraspinal structures and illustrate the importance of studying developmental
      circuits in the intact nervous system.

PMID- 16420423
TI  - Caspase-like activity is essential for long-term synaptic plasticity in the
      terrestrial snail Helix.
AB  - Although caspase activity in the nervous system of mollusks has not been
      described before, we suggested that these cysteine proteases might be involved in
      the phenomena of neuroplasticity in mollusks. We directly measured caspase-3
      (DEVDase) activity in the Helix lucorum central nervous system (CNS) using a
      fluorometrical approach and showed that the caspase-3-like immunoreactivity is
      present in the central neurons of Helix. Western blots revealed the presence of
      caspase-3-immunoreactive proteins with a molecular mass of 29 kDa. Staurosporin
      application, routinely used to induce apoptosis in mammalian neurons through the
      activating cleavage of caspase-3, did not result in the appearance of a smaller
      subunit corresponding to the active caspase in the snail. However, it did
      increase the enzyme activity in the snail CNS. This suggests differences in the
      regulation of caspase-3 activity in mammals and snails. In the snail CNS, the
      caspase homolog seems to possess an active center without activating cleavage
      typical for mammals. In electrophysiological experiments with identified snail
      neurons, selective blockade of the caspase-3 with the irreversible and cell
      permeable inhibitor of caspase-3 N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp
      (OMe)-fluoro-methylketone prevented development of the long-term stage of
      synaptic input sensitization, suggesting that caspase is necessary for normal
      synaptic plasticity in snails. The results of our study give the first direct
      evidence that the caspase-3-like activity is essential for long-term plasticity
      in the invertebrate neurons. This activity is presumably involved in removing
      inhibitory constraints on the storage of long-term memory.

PMID- 16420424
TI  - Motor learning changes GABAergic terminals on spinal motoneurons in normal rats.
AB  - The role of spinal cord plasticity in motor learning is largely unknown. This
      study explored the effects of H-reflex operant conditioning, a simple model of
      motor learning, on GABAergic input to spinal motoneurons in rats. Soleus
      motoneurons were labeled by retrograde transport of a fluorescent tracer and
      GABAergic terminals on them were identified by glutamic acid decarboxylase
      (GAD)67 immunoreactivity. Three groups were studied: (i) rats in which down
      conditioning had reduced the H-reflex (successful HRdown rats); (ii) rats in
      which down-conditioning had not reduced the H-reflex (unsuccessful HRdown rats)
      and (iii) unconditioned (naive) rats. The number, size and GAD density of
      GABAergic terminals, and their coverage of the motoneuron, were significantly
      greater in successful HRdown rats than in unsuccessful HRdown or naive rats. It
      is likely that these differences are due to modifications in terminals from
      spinal interneurons in lamina VI-VII and that the increased terminal number,
      size, GAD density and coverage in successful HRdown rats reflect and convey a
      corticospinal tract influence that changes motoneuron firing threshold and
      thereby decreases the H-reflex. GABAergic terminals in spinal cord change after
      spinal cord transection. The present results demonstrate that such spinal cord
      plasticity also occurs in intact rats in the course of motor learning and suggest
      that this plasticity contributes to skill acquisition.

PMID- 16420425
TI  - Blockade of mGluR glutamate receptors in the subthalamic nucleus ameliorates
      motor asymmetry in an animal model of Parkinson's disease.
AB  - It has been suggested that Group I metabotropic glutamate receptor antagonists
      could have potential therapeutic value in the treatment of Parkinson's disease.
      There is evidence that when given systemically, 2-methyl-6-(phenylethynyl)
      pyridine (MPEP), a metabotropic glutamate receptor type 5 (mGluR5) antagonist,
      produces anti-parkinsonian effects in animal models, but the site of action has
      not been directly established. In the present study, we examined whether the
      subthalamic nucleus (STN) and its output structures may mediate such an effect
      using a unilateral rat model of Parkinson's disease. A battery of simple
      behavioral tests, reliably sensitive to dopamine depletion, was applied
      consecutively: (i) prior to surgery; (ii) 3 weeks following a unilateral 6
      hydroxydopamine lesion of the substantia nigra pars compacta; (iii) at 1 h, 24 h
      and 4 days following a microinjection of MPEP, via an indwelling cannula, into
      the STN, entopeduncular nucleus (EP) or substantia nigra zona reticulata.
      Unilaterally dopamine-depleted animals typically had severe motor and
      sensorimotor asymmetries 3 weeks following surgery. Microinjection of 25 nmol
      MPEP into the STN of these animals significantly attenuated these asymmetries
      relative to vehicle. Further microinjections of lower doses (5 and 10 nmol)
      revealed a dose-response effect. Microinjection of MPEP into either the EP or
      substantia nigra zona reticulata was without effect. These data suggest that MPEP
      may act at the level of the STN to reduce glutamatergic overactivity and thereby
      induce anti-parkinsonian effects.

PMID- 16420426
TI  - Diversity of laminar connections linking periarcuate and lateral intraparietal
      areas depends on cortical structure.
AB  - Lateral prefrontal and intraparietal cortices have strong connectional and
      functional associations but it is unclear how their common visuomotor, perceptual
      and working memory functions arise. The hierarchical scheme of cortical
      processing assumes that prefrontal cortex issues 'feedback' projections to
      parietal cortex. However, the architectonic heterogeneity of these cortices
      raises the question of whether distinct areas have laminar-specific
      interconnections underlying their complex functional relationship. Using
      quantitative procedures, we showed that laminar-specific connections between
      distinct prefrontal (areas 46 and 8) and lateral intraparietal (LIPv, LIPd and
      7a) areas in Macaca mulatta, studied with neural tracers, varied systematically
      according to rules determined by the laminar architecture of the linked areas. We
      found that axons from areas 46 and rostral 8 terminated heavily in layers I-III
      of all intraparietal areas, as did caudal area 8 to area LIPv, suggesting
      'feedback' communication. However, contrary to previous assumptions, axons from
      caudal area 8 terminated mostly in layers IV-V of LIPd and 7a, suggesting
      'feedforward' communication. These laminar patterns of connections were highly
      correlated with consistent differences in neuronal density between linked areas.
      When neuronal density in a prefrontal origin was lower than in the intraparietal
      destination, most terminations were found in layer I with a concomitant decrease
      in layer IV. The opposite occurred when the prefrontal origin had a higher
      neuronal density than the target. These findings indicate that the neuronal
      density of linked areas can reliably predict their laminar connections and may
      form the basis of understanding the functional complexity of prefrontal
      intraparietal interactions in cognition.

PMID- 16420427
TI  - Increased mRNA levels of tyrosine hydroxylase and dopamine transporter in the VTA
      of male rats after chronic food restriction.
AB  - Dieting as a strategy to reduce body weight often fails as it causes food
      cravings leading to bingeing and weight regain. Evidence from several lines of
      research suggests the presence of shared elements for neural regulation of food
      and drug craving. We quantified the expression of eight genes involved in
      dopamine signalling in brain regions related to the mesolimbic and nigrostriatal
      dopamine system in male rats subjected to chronic food restriction using
      quantitative real-time polymerase chain reaction. Food restriction strongly
      increased mRNA levels of tyrosine hydroxylase and the dopamine transporter in the
      ventral tegmental area. Quantitative autoradiography indicated that the dopamine
      transporter was also upregulated at the protein level in the shell of the nucleus
      accumbens. However, these effects were not observed after acute food deprivation.
      We suggest that the results reflect a sensitization of the mesolimbic dopamine
      pathway characterized by increased clearance of extracellular dopamine in the
      nucleus accumbens shell. Such sensitization of the mesolimbic dopamine system may
      be one of the underlying causes for the food cravings that interfere with dietary
      compliance.

PMID- 16420428
TI  - Spatial discrimination of visually similar environments by hippocampal place
      cells in the presence of remote recalibrating landmarks.
AB  - Place cells in the rat hippocampus commonly show place-related firing activity in
      the animal's current environment. Here, we evaluated the capability of the place
      cell system to discriminate visually identical environments. Place cell activity
      was first recorded while rats moved freely in a cylinder divided into three
      connected sectors. Two sectors were visually identical whereas the third sector
      was made distinctive by the addition of visual and tactile cues. When in a given
      sector, the rats could not perceive the cues present in the other two sectors.
      Most cells had distinctive place fields in each sector, including the two
      identical sectors. To rule out the influence of non-controlled cues, rotations of
      the cylinder (+/- 120 degrees) were conducted. When successful, cylinder
      rotations resulted in equivalent field rotation for all cells. These results
      suggest that the place cell system is able to form a specific spatial
      representation for all sectors, so that the rat knows, at any time, in which
      sector it is currently located. Presumably, such discrimination relies on angular
      path integration in which the computational errors stemming from self-motion cues
      would be corrected by environmental landmarks provided by the distinctive sector.

PMID- 16420429
TI  - Hitting Ras where it counts: Ras antagonism in the basolateral amygdala inhibits
      long-term fear memory.
AB  - Several studies have implicated the Ras/mitogen-activated protein kinase (MAPK)
      pathway in Pavlovian fear conditioning. RasGRF1 knockout mice show significant
      deficits in acquisition of long-term fear memories and long-term potentaition
      (LTP) in the basolateral amygdala (BLA). MAPK kinase inhibition also impairs fear
      conditioning and amygdaloid LTP. However, there is no direct evidence to date for
      the involvement of Ras itself in fear conditioning. To address this issue, we
      examined the effects of intra-amygdala infusions of the selective Ras antagonist
      farnesylthiosalicylic acid (FTS) on the acquisition and expression of conditional
      freezing in rats. Micro-infusions of FTS into the BLA prior to contextual fear
      conditioning significantly impaired acquisition of long-term contextual fear
      memory in a dose-dependent manner. Post-training FTS infusions had no effect on
      acquisition of long-term fear memory. The effects of FTS on fear conditioning
      were specific for the BLA. Finally, intra-amygdala infusions of FTS inhibited
      MAPK activation in BLA. Collectively, these results provide further evidence for
      the involvement of amygdaloid Ras in the acquisition of long-term conditional
      fear memory.

PMID- 16420430
TI  - Neurons in dopamine-rich areas of the rat medial midbrain predominantly encode
      the outcome-related rather than behavioural switching properties of conditioned
      stimuli.
AB  - Midbrain dopamine neurons are phasically activated by a variety of sensory
      stimuli. It has been hypothesized that these activations contribute to reward
      prediction or behavioural switching. To test the latter hypothesis we recorded
      from 131 single neurons in the ventral tegmental area and retrorubral field of
      thirsty rats responding during a modified go/no-go task. One-quarter (n = 33) of
      these neurons responded to conditioned stimuli in the task, which varied
      according to the outcome with which they were associated (saccharin or quinine
      solution) and according to whether they triggered a switch in the ongoing
      sequence of the animal's behaviour ('behavioural switching'). Almost half the
      neurons (45%) responded differentially to saccharin- vs. quinine-conditioned
      stimuli; the activity of a minority (15%) correlated with an aspect of
      behavioural switching (mostly exhibiting changes from baseline activity in the
      absence of a behavioural switch) and one-third (33%) encoded various outcome
      switch combinations. The strongest response was excitation to the saccharin
      conditioned stimulus. Additionally, a proportion (38%) of neurons responded
      during outcome delivery, typically exhibiting inhibition during saccharin
      consumption. The neurons sampled did not fall into distinct clusters on the basis
      of their electrophysiological characteristics. However, most neurons that
      responded to the outcome-related properties of conditioned stimuli had long
      action potentials (> 1.2 ms), a reported characteristic of dopamine neurons.
      Moreover, responses to saccharin-conditioned stimuli were functionally akin to
      dopamine responses found in the macaque and rat nucleus accumbens responses
      observed within the same task. In conclusion, our data are more consistent with
      the reward-prediction than the behavioural switching hypothesis.

PMID- 16420431
TI  - Stimulation of D1-like or D2 dopamine receptors in the shell, but not the core,
      of the nucleus accumbens reinstates cocaine-seeking behaviour in the rat.
AB  - Although increases in dopamine transmission in the brain are clearly involved in
      the reinstatement of cocaine seeking, the role of nucleus accumbens dopamine in
      cocaine priming-induced reinstatement remains controversial. The goal of these
      experiments was to evaluate the relative contributions of D1-like and D2-like
      dopamine receptors in the nucleus accumbens core and shell in the reinstatement
      of cocaine-seeking behaviour. Initially, rats were trained to press a lever for
      cocaine (0.25 mg, i.v.) using a fixed-ratio 5 (FR5) schedule of reinforcement.
      Responding was then extinguished by substituting saline for cocaine. During the
      reinstatement phase, subtype-specific dopamine receptor agonists were
      microinjected into the nucleus accumbens core or medial shell in order to assess
      their ability to induce cocaine seeking. Administration of the D1/D5 dopamine
      receptor agonist SKF-81297 (1.0 microg) into the nucleus accumbens shell, but not
      core, reinstated drug-seeking behaviour. Similarly, microinjection of quinpirole
      (3.0 microg), a D2/D3 dopamine receptor agonist, into the nucleus accumbens shell
      and not core reinstated drug-seeking behaviour. In contrast, administration of
      the D3- or D4-preferring dopamine receptor agonists PD 128,907 (1.5 and 3.0
      microg) and PD 168,077 (0.3 and 3.0 microg), respectively, did not promote
      reinstatement when administered into either the core or the shell. Taken
      together, these results indicate that activation of D1/D5 or D2 dopamine
      receptors, in the limbic shell subregion of the nucleus accumbens but not the
      basal ganglia-orientated accumbens core, promotes the reinstatement of cocaine
      seeking behaviour.

PMID- 16420432
TI  - Paradoxical effects of prodynorphin gene deletion on basal and cocaine-evoked
      dopaminergic neurotransmission in the nucleus accumbens.
AB  - Quantitative and conventional microdialysis were used to investigate the effects
      of constitutive deletion of the prodynorphin gene on basal dopamine (DA) dynamics
      in the nucleus accumbens (NAc) and the responsiveness of DA neurons to an acute
      cocaine challenge. Saline- and cocaine-evoked locomotor activity were also
      assessed. Quantitative microdialysis revealed that basal extracellular DA levels
      were decreased, while the DA extraction fraction, an indirect measure of DA
      uptake, was unchanged in dynorphin (DYN) knockout (KO) mice. The ability of
      cocaine to increase NAc DA levels was reduced in KO. Similarly, cocaine-evoked
      locomotor activity was decreased in KO. The selective kappa opioid receptor
      agonist U-69593 decreased NAc dialysate DA levels in wildtype mice and this
      effect was enhanced in KO. Administration of the selective kappa opioid receptor
      (KOPr) antagonist nor-binaltorphimine to KO mice attenuated the decrease in
      cocaine-induced DA levels. However, it was ineffective in altering the decreased
      locomotor response to cocaine. These studies demonstrate that constitutive
      deletion of prodynorphin is associated with a reduction of extracellular NAc DA
      levels and a decreased responsiveness to acute cocaine. Data regarding the
      effects of U-69593 and nor-binaltorphimine in KO suggest that the kappa opioid
      receptor is up-regulated as a consequence of prodynorphin gene deletion and that
      this adaptation underlies the decrease in basal DA dynamics and cocaine-evoked DA
      levels observed in DYN KO mice. These findings suggest that the phenotype of DYN
      KO mice is not solely due to loss of endogenous opioid peptide but also reflects
      developmental compensations that occur at the level of the opioid receptor.

PMID- 16420433
TI  - LTP in the lateral amygdala during cocaine withdrawal.
AB  - The amygdala plays key roles in several aspects of addiction to drugs of abuse.
      This brain structure has been implicated in behaviours that reflect drug reward,
      drug seeking, and the aversive effects of drug withdrawal. Using a model that
      involves repeated cocaine injections to approximate 'binge' intoxication, we show
      in rats that during cocaine withdrawal, the impact of rewarding brain stimulation
      is attenuated, as quantified by alterations in intracranial self-stimulation
      (ICSS) behaviour. These behavioural signs of withdrawal are accompanied by
      enhancements of glutamatergic synaptic transmission within the lateral amygdala
      (LA) that occlude electrically induced long-term potentiation (LTP) in tissue
      slices. Synaptic enhancements during periods of cocaine withdrawal are
      mechanistically similar to LTP induced with electrical stimulation in control
      slices, as both forms of synaptic plasticity involve an increase in glutamate
      release. These results suggest that mechanisms of LTP within the amygdala are
      recruited during withdrawal from repeated exposure to cocaine. As such, they
      raise the possibility that the development and maintenance of addictive
      behaviours may involve, at least in part, mechanisms of synaptic plasticity
      within specific amygdala circuits.

PMID- 16420434
TI  - Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion
      of BACE1.
AB  - Transgenic mouse models of Alzheimer's disease (AD) exhibit amyloid-beta (Abeta)
      accumulation and related cognitive impairments. Although deficits in hippocampus
      dependent place learning have been well characterized in Alzheimer's transgenic
      mice, little is known about temporal memory function in these AD models. Here, we
      applied trace fear conditioning to two different Alzheimer's mouse models and
      investigated the relationship between pathogenic Abeta and temporal memory
      deficits. This behavioral test requires hippocampus-dependent temporal memory
      processing as the conditioned and unconditioned stimuli are separated by a trace
      interval of 30 s. We found that both amyloid precursor protein (APP) transgenic
      (Tg2576) and APP/presenilin (PS)1 transgenic (Tg6799) mice were impaired in
      memorizing this association across the time gap. Both transgenic groups performed
      as well as wild-type control mice in delay fear conditioning when the trace
      interval was removed, indicating that the trace conditioning deficits are
      hippocampus-specific. Importantly, Tg6799 mice engineered to lack the major
      Alzheimer's beta-secretase (beta-site APP-cleaving enzyme 1: BACE1) showed
      behavioral rescue from temporal memory deficits. Elevated levels of soluble Abeta
      oligomers found in Tg6799+ mouse brains returned to wild-type control levels
      without changes in APP/PS1 transgene expression in BACE1-/- * Tg6799+ bigenic
      mouse brains, suggesting Abeta oligomers as potential mediators of memory loss.
      Thus, trace fear conditioning is a useful assay to test the mechanisms and
      therapeutic interventions for Abeta-dependent deficits in temporal associative
      memory. Our gene-based approach suggests that lowering soluble Abeta oligomers by
      inhibiting BACE1 may be beneficial for alleviating cognitive disorders in AD.

PMID- 16420435
TI  - Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by
      behavioural stress and environmental enrichment.
AB  - Behavioural experience (e.g. chronic stress, environmental enrichment) can have
      long-lasting effects on cognitive functions. Because activity-dependent
      persistent changes in synaptic strength are believed to mediate memory processes
      in brain areas such as hippocampus, we tested whether behaviour has also long
      lasting effects on synaptic plasticity by examining the induction of long-term
      potentiation (LTP) and long-term depression (LTD) in slices of hippocampal CA1
      obtained from rats either 7-9 months after social defeat (behavioural stress) or
      3-5 weeks after 5-week exposure to environmental enrichment. Compared with age
      matched controls, defeated rats showed markedly reduced LTP. LTP was even
      completely impaired but LTD was enhanced in defeated and, subsequently,
      individually housed (during the 7-9-month period after defeat) rats. However,
      increasing stimulus intensity during 100-Hz stimulation resulted in significant
      LTP. This suggests that the threshold for LTP induction is still raised and that
      for LTD lowered several months after a short stressful experience. Both LTD and
      LTP were enhanced in environmentally enriched rats, 3-5 weeks after enrichment,
      as compared with age-matched controls. Because enrichment reduced paired-pulse
      facilitation, an increase in presynaptic release, facilitating both LTD and LTP
      induction, might contribute to enhanced synaptic changes. Consistently,
      enrichment reduced the number of 100-Hz stimuli required for inducing LTP. But
      enrichment may also actually enhance the range of synaptic modification. Repeated
      LTP and LTD induction produced larger synaptic changes in enriched than in
      control rats. These data reveal that exposure to very different behavioural
      experiences can produce long-lasting effects on the susceptibility to synaptic
      plasticity, involving pre- and postsynaptic processes.

PMID- 16420436
TI  - Spinal cord compression and dorsal root injury cause up-regulation of activating
      transcription factor-3 in large-diameter dorsal root ganglion neurons.
AB  - Spinal cord injury causes damage to ascending and descending tracts, as well as
      to local circuits, but relatively little is known about the effect of such injury
      on sensory neurons located within adjoining ganglia. We have therefore used
      immunocytochemistry for activating transcription factor-3 (ATF3), a sensitive
      marker of axonal damage, in order to examine the effects of spinal cord injury in
      rats on dorsal root ganglion (DRG) neurons. A 50-g static compression injury
      applied to the dorsal surface of the T12 thoracic spinal cord led to an up
      regulation of ATF3 that was maximal at 1 day and affected 12-14% of DRG neurons
      in ganglia caudal to the injury (T13-L3). A similar response was seen after a T12
      hemisection that transected the dorsal columns except that compression injury,
      but not hemisection, also evoked ATF3 expression in ganglia just rostral to the
      injury (T10, T11). ATF3 was up-regulated exclusively in DRG neurons that were of
      large diameter and immunoreactive for heavy neurofilament. Small-diameter cells,
      including the population that binds the lectin Grifffonia simplicifolia IB4, did
      not express ATF3 immunoreactivity. A similar pattern of ATF3 expression was
      induced by dorsal rhizotomy. The data show for the first time that ATF3 is up
      regulated after spinal cord and dorsal root injury, but that this up-regulation
      is confined to the large-diameter cell population.

PMID- 16420437
TI  - Decrease in parvalbumin-expressing neurons in the hippocampus and increased
      phencyclidine-induced locomotor activity in the rat methylazoxymethanol (MAM)
      model of schizophrenia.
AB  - Treatment of rats with methylazoxymethanol (MAM) on gestational day (GD)17
      disrupts corticolimbic development in the offspring (MAM-GD17 rats) and leads to
      abnormalities in adult MAM-GD17 rats resembling those described in schizophrenic
      patients. The underlying changes in specific cortical and limbic cell populations
      remain to be characterised. In schizophrenia, decreases in inhibitory gamma
      aminobutyric acid (GABA)-containing interneurons that express the calcium-binding
      protein parvalbumin have been reported in the prefrontal cortex and hippocampus.
      In this study we analysed the expression of parvalbumin (PV), calretinin (CR) and
      calbindin (CB) in the prefrontal cortex and hippocampus of MAM-GD17 rats.
      Exposure in utero to MAM led to a significant decrease in the number of neurons
      expressing PV in the hippocampus, but not the prefrontal cortex. Neurons
      expressing CR or CB were not affected in either structure. The neurochemical
      changes in MAM-GD17 rats were accompagnied by increased hyperlocomotion after
      administration of phencyclidine (PCP), analogous to the hypersensitivity of
      schizophrenic patients to PCP. Therefore, the developmental MAM-GD17 model
      reproduces key neurochemical and behavioural features that reflect cortical and
      subcortical dysfunction in schizophrenia, and could be a useful tool in the
      development of new antipsychotic drugs.

PMID- 16420439
TI  - Identification of ventricular-side-enriched molecules regulated in a stage
      dependent manner during cerebral cortical development.
AB  - Radial glial cells are the main component of the embryonic cortical ventricular
      zone (VZ), producing deep-layer excitatory neurons in the early stage and upper
      layer excitatory neurons in the late stage of development. Previous studies have
      suggested that the laminar fate of deep-layer neurons might be determined by
      early-stage-specific secretory or transmembrane molecules (S/TMs) in the VZ.
      However, the different properties required to produce the different types of
      neurons in early-stage and late-stage VZ cells are largely unknown. Herein, we
      investigated the stage-dependent transcriptional profiles of the ventricular side
      of the mouse cortex, which was manually dissected at embryonic day (E)12, E14 and
      E16, and identified 3985 'VZ-enriched' genes, regulated stage-dependently, by
      GeneChip analysis. These molecules were classified into nine types based on stage
      dependent regulation patterns. Prediction programs for the S/TMs revealed 659 'VZ
      enriched' S/TMs. In situ hybridization and real-time PCR analysis for several of
      these molecules showed results consistent with the statistical analysis of the
      GeneChip experiments. Moreover, we identified 17 cell cycle-related early-stage
      and 'VZ-enriched' molecules. These molecules included not only those involved in
      cell cycle progression, but also essential molecules for DNA double-strand break
      repair, such as Rad51 and Rpa1. These results suggest that the early stage-VZ
      cells, which produce both deep- and upper-layer neurons, and the late-stage VZ
      cells, which produce only upper-layer neurons, are intrinsically different. The
      gene lists presented here will be useful for the investigation of stage-dependent
      changes in VZ cells and their regulatory mechanisms in the developing cortex.

PMID- 16420438
TI  - Macrophages and neurons are targets of retinoic acid signaling after spinal cord
      contusion injury.
AB  - The physiological reactions after spinal cord injury are accompanied by local
      synthesis of the transcriptional activator retinoic acid (RA). RA exerts its
      effects by binding to retinoic acid receptors (RAR) which heterodimerize with
      retinoid X receptors (RXR) and then act as ligand-activated transcription
      factors. To identify possible cellular targets of RA we investigated protein
      levels and cellular distribution of retinoid receptors in the rat spinal cord at
      4, 7, 14 and 21 days after a contusion injury. In the nonlesioned spinal cord,
      immunoreactivity for RARalpha, RXRalpha, RXRbeta and RXRgamma was localized in
      the cytosol of neurons, that of RXRalpha and RXRbeta in astrocytes and that of
      RARalpha, RXRalpha and RXRgamma in some oligodendrocytes. After contusion injury
      RARalpha and all RXRs appeared in the cell nuclei of reactive microglia and
      macrophages. This nuclear staining began at 4 days, was most prominent at 7 and
      14 days and had decreased at 21 days after injury. A similar nuclear
      translocation was also observed for the RARalpha, RXRalpha and RXRbeta staining
      in neurons situated around the border of the contusion. These observations
      suggest that RA participates as a signal for the physiological responses of
      microglia and neurons after CNS injury.

PMID- 16420440
TI  - Anp32e/Cpd1 regulates protein phosphatase 2A activity at synapses during
      synaptogenesis.
AB  - Anp32e/Cpd1, a member of the acidic nuclear phosphoprotein (Anp)32 family, is
      characterized by the presence of an amino terminal domain containing four leucine
      rich repeats and a carboxyl-terminal low-compositional complexity acidic region.
      In previous studies performed to understand the biological role of Anp32e/Cpd1,
      we showed a predominant presence of Anp32e/Cpd1 in the nucleus. However, when
      Anp32e/Cpd1 is in the cytoplasm, it co-localizes spatially with protein
      phosphatase 2A (PP2A) near cell membranes, far from the synapses. In the present
      work, we show that Anp32e/Cpd1 is also present as a membrane-bound 74/76-kDa
      protein with a widespread distribution in the brain. We reveal that the
      expression, synthesis and half-life of this high-molecular-weight form of
      Anp32e/Cpd1 are spatially and temporally correlated with the cerebellar
      synaptogenesis period. We demonstrate that synaptic Anp32e/Cpd1 co-localizes,
      interacts and inhibits PP2A activity, and that phosphorylation of Anp32/Cpd1 is
      required for the Anp32e-PP2A interaction. Also, subcellular localization was
      shown with electronic microscopy. Finally, we examine Anp32e/Cpd1 and PP2A
      distribution in two ataxic mutant models, weaver and staggerer, and show that
      their co-localization in Purkinje cell dendrites depends on parallel
      fibre/Purkinje cell contacts. Based on these observations, we propose that
      Anp32e/Cpd1 mediates synaptogenesis process by modulating PP2A activity.

PMID- 16420441
TI  - Effects of Emx2 inactivation on the gene expression profile of neural precursors.
AB  - Emx2 plays a crucial role in the development of the diencephalon and dorsal
      telencephalon. Thus, Emx2-null mutants have abnormal cortical lamination and a
      reduction in size of the caudal and medial areas of the prosencephalon. Emx2 is
      expressed in neural precursors of the subventricular zone in vivo and in cultured
      neurospheres in vitro where it controls the size of the transit-amplifying
      population, affecting proliferation and clonal efficiency of neural stem cells.
      To identify the cellular processes mastered by Emx2, and possibly the molecular
      mechanisms by which the gene exerts its action, we compared the expression
      profile of cultured neurospheres derived from wild-type and Emx2-null mouse
      embryos. The differential expression of several genes was also confirmed by
      semiquantitative RT-PCR, real-time PCR and cytofluorimetric analysis in different
      preparations of neurospheres, and by in situ hybridization. The gene expression
      profile suggested a role for Emx2 in regulating the differentiation and migration
      properties of neural precursor cells. This involvement was confirmed in vitro,
      where the altered clonogenicity and impaired migration of Emx2-null cells were
      partially corrected by transduction of the Emx2 gene. Taken together, our results
      indicate that Emx2 is indeed involved in the transition between resident early
      progenitors (perhaps stem cells) and more mature precursors capable of migrating
      out of the ventricular zone, becoming postmitotic and differentiating into the
      appropriate cell type, and help explain the alterations observed in the brains of
      knock-out mice.

PMID- 16420442
TI  - Developmental changes of CaMKII localization, activity and function during
      postembryonic CNS remodelling in Manduca sexta.
AB  - Insect metamorphosis is a compelling example of postembryonic remodelling of
      neuronal structure and synaptic connectivity as larval and adult behaviours place
      distinct demands on the CNS. Holometabolous insects such as the moth Manduca
      sexta have long served as suitable models for the study of steroid effects on CNS
      remodelling, but activity and calcium-dependent mechanisms have been found to act
      in concert with hormonal signals. This study examines developmental changes in
      the localization and the activational state of CaMKII during postembryonic
      Manduca CNS remodelling. Western blotting, CaMKII purification and
      autophosphorylation with gamma(32)P-ATP indicate that the lepidopteran CNS may
      contain only one CaMKII isoform. In situ immunohistochemistry reveals
      developmental changes in the expression patterns of CaMKII in different types of
      thoracic neurons and in different neuronal compartments. Early pupal life is
      characterized by an increase in postsynaptic CaMKII localization, which coincides
      with a developmental increase in CaMKII activation. Both events correlate
      temporally with motoneuron dendritic filopodia collapse and rapid synaptogenesis,
      indicating a possible functional role for CaMKII for the postembryonic
      development of invertebrate motor circuitry. Substrate phosphorylation assays
      demonstrate that CaMKII activity in the ventral nerve cord reflects changes in
      calcium influx through voltage-activated channels as occurring in vivo during
      normal development.

PMID- 16420443
TI  - Characterization of the glycinergic input to bipolar cells of the mouse retina.
AB  - Glycine and gamma-aminobutyric acid (GABA) are the major inhibitory transmitters
      of the mammalian retina, and bipolar cells receive GABAergic and glycinergic
      inhibition from multiple amacrine cell types. Here we evaluated the functional
      properties and subunit composition of glycine receptors (GlyRs) in bipolar cells.
      Patch-clamp recordings were performed from retinal slices of wild-type,
      GlyRalpha1-deficient (Glra1(spd-ot)) and GlyRalpha3-deficient (Glra3(-/-)) mice.
      Whole-cell currents following glycine application and spontaneous inhibitory
      postsynaptic currents (IPSCs) were analysed. During the recordings the cells were
      filled with Alexa 488 and, thus, unequivocally identified. Glycine-induced
      currents of bipolar cells were picrotoxinin-insensitive and thus represent
      heteromeric channels composed of alpha and beta subunits. Glycine-induced
      currents and IPSCs were absent from all bipolar cells of Glra1(spd-ot) mice,
      indicating that GlyRalpha1 is an essential subunit of bipolar cell GlyRs. By
      comparing IPSCs of bipolar cells in wild-type and Glra3(-/-) mice, no
      statistically significant differences were found. OFF-cone bipolar (CB) cells
      receive a strong glycinergic input from AII amacrine cells, that is
      preferentially based on the fast alpha1beta-containing channels (mean decay time
      constant tau = 5.9 +/- 1.4 ms). We did not observe glycinergic IPSCs in ON-CB
      cells and could elicit only small, if any, glycinergic currents. Rod bipolar
      cells receive a prominent glycinergic input that is mainly mediated by alpha1beta
      containing channels (tau = 5.5 +/- 1.6 ms). Slow IPSCs, the characteristic of
      GlyRs containing the alpha2 subunit, were not observed in bipolar cells. Thus,
      different bipolar cell types receive kinetically fast glycinergic inputs,
      preferentially mediated by GlyRs composed of alpha1 and beta subunits.

PMID- 16420444
TI  - ATF3 expression in L4 dorsal root ganglion neurons after L5 spinal nerve
      transection.
AB  - Activating transcription factor 3 (ATF3) is a widely used marker of damaged
      primary sensory neurons that is induced in essentially all dorsal root ganglion
      (DRG) neurons by spinal nerve axotomy. Whether such injuries induce its
      expression in neurons of adjacent DRGs remains unknown. Following L5 spinal nerve
      ligation, experimental but not sham-operated rats develop thermal and mechanical
      hypersensitivity. In the L4 DRG, 11-12% of neurons were ATF3 positive by 1 day
      post-surgery, and numbers remain unchanged at 2 weeks. Importantly, sham exposure
      of the L5 spinal nerve produced a nearly identical number of ATF3-positive
      neurons in the L4 DRG and also a substantial increase in the L5 DRG, with a
      similar time-course to experimental animals. There was no correlation between
      behaviour and magnitude of ATF3 expression. Co-localization studies with the DRG
      injury markers galanin, neuropeptide Y and nitric oxide synthase (NOS) showed
      that approximately 75, 50 and 25%, respectively, of L4 ATF3-positive neurons co
      expressed these markers after L5 transection or sham surgery. Additionally,
      increases in galanin and NOS were seen in ATF3-negative neurons in L4. Our
      results strongly suggest that the surgical exposure of spinal nerves induces ATF3
      in the L4-5 DRG, irrespective of whether the L5 nerve is subsequently cut. This
      probably reflects minor damage to the neurons or their axons but nevertheless is
      sufficient to induce phenotypic plasticity. Caution is therefore warranted when
      interpreting the phenotypic plasticity of DRG neurons in adjacent ganglia in the
      absence of positive evidence that they are not damaged.

PMID- 16420445
TI  - Localization and function of pre- and postsynaptic kainate receptors in the rat
      globus pallidus.
AB  - Kainate receptors (KARs) are widely expressed the basal ganglia. In this study,
      we used electron microscopic immunocytochemistry and whole-cell recording
      techniques to examine the localization and function of KARs in the rat globus
      pallidus (GP). Dendrites were the most common immunoreactive elements, while
      terminals forming symmetric or asymmetric synapses and unmyelinated axons
      comprised most of the presynaptic labeling. To determine whether synaptically
      released glutamate activates KARs, we recorded excitatory postsynaptic currents
      (EPSCs) in the GP following single-pulse stimulation of the internal capsule. 4
      (8-Methyl-9H-1,3-dioxolo[4,5 h]{2,3}benzodiazepine-5-yl)-benzenamine
      hydrochloride (GYKI 52466, 100 microm), an alpha-amino-3-hydroxyl-5-methyl-4
      isoxazole propionic acid (AMPA) receptor antagonist, reduced but did not
      completely block evoked EPSCs. The remaining EPSC component was mediated through
      activation of KARs because it was abolished by 6-cyano-7-nitroquinoxaline-2, 3
      dione (CNQX), an AMPA/KAR antagonist. The rise time (10-90%) and decay time
      constant (tau) for those EPSCs were longer than those of AMPA-mediated EPSCs
      recorded before GYKI 52466 application. KAR activation inhibited EPSCs. This
      inhibition was associated with a significant increase in paired-pulse
      facilitation ratio, suggesting a presynaptic action of KAR. KAR inhibition of
      EPSCs was blocked by the G-protein inhibitor, N-ethylmaleimide (NEM), or the
      protein kinase C (PKC) inhibitor calphostin C. Our results demonstrate that KAR
      activation has dual effects on glutamatergic transmission in the rat GP: (1) it
      mediates small-amplitude EPSCs; and (2) it reduces glutamatergic synaptic
      transmission through a presynaptic G-protein coupled, PKC-dependent, metabotropic
      mechanism. These findings provide evidence for the multifarious functions of KARs
      in regulating synaptic transmission, and open up the possibility for the
      development of pharmacotherapies to reduce the hyperactive subthalamofugal
      projection in Parkinson's disease.

PMID- 16420446
TI  - Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after
      neonatal cerebral hypoxia-ischemia.
AB  - The effectiveness of hypothermia in preventing ischemic brain damage depends on
      when it is started. The purpose of this study was to investigate the effects of
      temperature reduction during a hypoxic-ischemic (HI) insult on brain injury and
      signalling pathways of neuronal cell death and survival. Seven-day-old mice were
      subjected to left common carotid artery ligation and hypoxia (10% oxygen) at
      different temperatures (37, 36 or 34 degrees C) for 50 min. Brain injury at 7
      days post-HI was significantly reduced from 67.4% at 37 degrees C to 31.6% at 36
      degrees C and 10% at 34 degrees C, with no observable injury in the cortex of the
      34 degrees C group. Cytochrome c release, caspase-3 activation and apoptosis
      inducing factor translocation from mitochondria to nuclei were all significantly
      inhibited after intraischemic temperature reduction. Concurrently, the cell
      survival signalling pathway involving Akt was significantly sustained (the
      phosphorylated form of Akt was maintained) when the hypoxia temperature was
      decreased. These results indicate that intraischemic hypothermia diminished
      apoptosis through inhibition of both caspase-dependent and caspase-independent
      neuronal cell death pathways and promoted cell survival by inhibition of
      phosphorylated Akt dephosphorylation in the neonatal brain, thereby preventing
      neuronal cell death.

PMID- 16420447
TI  - Neurogenesis in the adult spinal cord in an experimental model of multiple
      sclerosis.
AB  - Multiple sclerosis is an inflammatory disease of the central nervous system
      characterized by inflammation, demyelination, axonal degeneration and
      accumulation of neurological disability. Previously, we demonstrated that stem
      cells constitute a possible endogenous source for remyelination. We now addressed
      the question of whether neurogenesis can occur in neuroinflammatory lesions. We
      demonstrated that, in experimental autoimmune encephalomyelitis, induced in rats
      1,1'-dioctadecyl-6,6'-di(4sulphopentyl)-3,3,3',3'tetramethylindocarbocyanin(DiI)
      labelled ependymal cells not only proliferated but descendants migrated to the
      area of neuroinflammation and differentiated into cells expressing the neuronal
      markers beta-III-tubulin and NeuN. Furthermore, these cells were immunoreactive
      for bromodeoxyuridine and PCNA, markers for cells undergoing cell proliferation.
      Using the whole-cell patch-clamp technique on freshly isolated 1, DiI-labelled
      cells from spinal cord lesions we demonstrated the ability of these cells to fire
      overshooting action potentials similar to those of immature neurones. We thus
      provide the first evidence for the initiation of neurogenesis in
      neuroinflammatory lesions in the adult spinal cord.

PMID- 16420448
TI  - Extracellular matrix molecules and synaptic plasticity: immunomapping of
      intracellular and secreted Reelin in the adult rat brain.
AB  - Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron
      populations in the developing and adult rodent brain. Secreted Reelin triggers a
      complex signaling pathway by binding lipoprotein and integrin membrane receptors
      in target cells. Reelin signaling regulates migration and dendritic growth in
      developing neurons, while it can modulate synaptic plasticity in adult neurons.
      To identify which adult neural circuits can be modulated by Reelin-mediated
      signaling, we systematically mapped the distribution of Reelin in adult rat brain
      using sensitive immunolabeling techniques. Results show that the distribution of
      intracellular and secreted Reelin is both very widespread and specific. Some
      interneuron and projection neuron populations in the cerebral cortex contain
      Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these
      cells are preferentially located in striosomes. Some thalamic nuclei contain
      Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals
      that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic
      thalamic interneurons. High local concentrations of extracellular Reelin
      selectively outline several dendrite spine-rich neuropils. Together with previous
      mRNA data, our observations suggest abundant axoplasmic transport and secretion
      in pathways such as the retino-collicular tract, the entorhino-hippocampal
      ('perforant') path, the lateral olfactory tract or the parallel fiber system of
      the cerebellum. A preferential secretion of Reelin in these neuropils is
      consistent with reports of rapid, activity-induced structural changes in adult
      brain circuits.

PMID- 16420449
TI  - Depression of retinogeniculate synaptic transmission by presynaptic D(2)-like
      dopamine receptors in rat lateral geniculate nucleus.
AB  - Extraretinal projections onto neurons in the dorsal lateral geniculate nucleus
      (dLGN) play an important role in modifying sensory information as it is relayed
      from the visual thalamus to neocortex. The dLGN receives dopaminergic innervation
      from the ventral tegmental area; however, the role of dopamine in synaptic
      transmission in dLGN has not been explored. In the present study, whole cell
      recordings were obtained to examine the actions of dopamine on glutamatergic
      synaptic transmission. Dopamine (2-100 microm) strongly suppressed excitatory
      synaptic transmission in dLGN relay neurons that was evoked by optic tract
      stimulation and mediated by both N-methyl-d-aspartate and non-N-methyl-d
      aspartate glutamate receptors. In contrast, dopamine did not alter inhibitory
      synaptic transmission arising from either dLGN interneurons or thalamic reticular
      nucleus neurons. The suppressive action of dopamine on excitatory synaptic
      transmission was mimicked by the D(2)-like dopamine receptor agonist
      bromocriptine (2-25 microm) but not by the D(1)-like receptor agonist SKF38393
      (10-25 microm). In addition, the dopamine-mediated suppression was antagonized by
      the D(2)-like receptor antagonist sulpiride (10-20 microm) but not by the D(1)
      like receptor antagonist SCH23390 (5-25 microm). The dopamine-mediated decrease
      in evoked excitatory postsynaptic current amplitude was accompanied by an
      increase in the magnitude of paired-pulse depression. Furthermore, dopamine also
      reduced the frequency but not the amplitude of miniature excitatory postsynaptic
      currents. Taken together, these data suggest that dopamine may act
      presynaptically to regulate the release of glutamate at the retinogeniculate
      synapse and modify transmission of visual information in the dLGN.

PMID- 16420450
TI  - Cytosolic labile zinc: a marker for apoptosis in the developing rat brain.
AB  - Cytosolic zinc accumulation was thought to occur specifically in neuronal death
      (necrosis) following acute injury. However, a recent study demonstrated that zinc
      accumulation also occurs in adult rat neurons undergoing apoptosis following
      target ablation, and in vitro experiments have shown that zinc accumulation may
      play a causal role in various forms of apoptosis. Here, we examined whether
      intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis
      during development. Embryonic and newborn Sprague-Dawley rat brains were double
      stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labelling (TUNEL) detection of apoptosis and immunohistochemical detection of
      stage-specific neuronal markers, such as nestin, proliferating cell nuclear
      antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results
      revealed that apoptotic cell death occurred in neurons of diverse stages (neural
      stem cells, and dividing, young and adult neurons) throughout the brain during
      the embryonic and early postnatal periods. Further staining of brain sections
      with acid fuchsin or zinc-specific fluorescent dyes showed that all of the
      apoptotic neurons were acidophilic and contained labile zinc in their cell
      bodies. Cytosolic zinc accumulation was also observed in cultured cortical
      neurons undergoing staurosporine- or sodium nitroprusside (SNP)-induced
      apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N',N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN) reduced SNP-induced apoptosis but not
      staurosporine-induced apoptosis, indicating that cytosolic zinc accumulation does
      not play a causal role in all forms of apoptosis. Finally, the specific cytosolic
      zinc accumulation may have a practical application as a relatively simple marker
      for neurons undergoing developmental apoptosis.

PMID- 16420451
TI  - Slow oscillatory activity of rat globus pallidus neurons in vitro.
AB  - The neurons in the external segment of the pallidum in the primate develop a
      characteristic firing pattern consisting of alternately occurring long, 2-20 s,
      strongly active phases and long completely silent phases when the subthalamo
      pallidal excitatory inputs are blocked. The induction of the activity might be a
      factor in the development of dyskinesias after the loss of subthalamic output. In
      this study, we used globus pallidus (GPe) slice preparations obtained from
      juvenile rats to examined the conditions that support the alternatively occurring
      long depolarized and hyperpolarized phases which we refer to as the slow
      oscillation (SO). SO was not induced by the blockade of glutamatergic inputs but
      was induced by treatments that depolarized dendrites and, at the same time,
      hyperpolarized the somata with current injections. The treatments included
      elevation of extracellular K(+), application of K-current blockers and the
      lowering of extracellular Ca(2+). Application of TTX or intracellular BAPTA
      injection blocked the SO, while the SO could be maintained in hyperpolarization
      activated inward current blockers, organic Ca-current blockers and up to 200
      microm CdCl(2). These results suggest that Na currents play a major role in the
      generation of SO in vitro. It can be speculated that Na currents are involved in
      the development of active phases observed in the GPe after blockade of the
      glutamatergic inputs in vivo and that the unique property of GPe neurons in
      maintaining strong activity after the elimination of the glutamatergic driving
      force contributes to the development of motor disorders such as dyskinesia.

PMID- 16420452
TI  - Intracellular acidification in neurons induced by ammonium depends on KCC2
      function.
AB  - The Cl(-)-extruding neuron-specific K(+)-Cl(-) cotransporter KCC2, which
      establishes hyperpolarizing inhibition, can transport NH(4) (+) instead of K(+).
      It is, however, not clear whether KCC2 provides the only pathway for neuronal
      NH(4) (+) uptake. We therefore investigated NH(4) (+) uptake in cultured rat
      brain neurons. In neurons cultured for > 4 weeks, the response to NH(4)Cl
      applications (5 mM) consisted of an alkaline shift which reversed to an acid
      shift within seconds. Rebound acid shifts which followed brief applications of
      NH(4)Cl were blocked by furosemide (100 microM). They were rather insensitive to
      bumetanide (1 and 100 microM), in contrast to those induced in cultured glial
      cells. Rebound acid shifts persisted in the presence of 1 mM Ba(2+) and in Na(+)
      free solution but were inhibited by extracellular K(+). In neurons with
      depolarizing GABA responses, indicating the absence of functional KCC2,
      applications of NH(4)Cl barely induced an acidosis. However, large rebound acid
      shifts occurred in neurons that had changed their GABA response from Ca(2+)
      increases to Ca(2+) decreases. Rebound acid shifts continued to increase even
      after the change in the GABA response had occurred and could be induced earlier
      in neurons transfected with KCC2 cDNA. We conclude that KCC2 provides the main
      pathway for fast neuronal NH(4) (+) uptake. Therefore, NH(4)Cl-induced rebound
      acid shifts can be used to indicate the development of KCC2 function. Further,
      the well known up-regulation of KCC2 function during development has the
      inevitable consequence of opening a major pathway for NH(4) (+) influx, which can
      be relevant under pathophysiological conditions.

PMID- 16420454
TI  - Medial prefrontal cortex NMDA receptors and nitric oxide modulate the
      parasympathetic component of the baroreflex.
AB  - The ventral portion of the medial prefrontal cortex (vMPFC) is involved in the
      modulation of the parasympathetic component of the baroreflex. In the present
      study, we verified the effect of blockade of vMPFC glutamatergic receptors and
      nitric oxide synthases (NOS) on the parasympathetic component of baroreflex in
      awake rats. Bilateral microinjection of the non-selective ionotropic glutamate
      antagonist kynurenic acid (KYN) into the vMPFC caused a shift of the threshold of
      reflex bradycardia toward higher pressures in response to increases in mean
      arterial pressure (MAP) caused by intravenous infusion of phenylephrine, thus
      indicating a tonic facilitatory influence action of vMPFC glutamate receptors on
      the parasympathetic component of the baroreflex. The effect of blockade of vMPFC
      NMDA receptors by AP7 was similar to that observed after KYN, suggesting
      mediation via NMDA receptors. Pretreatment with the NOS inhibitor L-NAME or the
      specific neural NOS (nNOS) N(omega)-propyl-l-arginine microinjected in the vMPFC
      caused a shift of the reflex threshold toward higher pressures that was similar
      to that observed after blockade of NMDA receptors, thus indicating participation
      of the NO/NMDA-receptor pathway in the vMPFC modulation of the parasympathetic
      component of the baroreflex. In conclusion, our data indicate that glutamatergic
      neurotransmission in the vMPFC has a tonic facilitatory influence on the
      parasympathetic component of the baroreflex. Because local treatment with either
      the nNOS inhibitor N(omega)-propyl-l-arginine or the specific NMDA antagonist AP7
      had similar effects on the baroreflex, it is also suggested that this modulation
      involves an NMDA-NO interaction within the vMPFC.

PMID- 16420453
TI  - Propofol block of I(h) contributes to the suppression of neuronal excitability
      and rhythmic burst firing in thalamocortical neurons.
AB  - Although the depressant effects of the general anesthetic propofol on
      thalamocortical relay neurons clearly involve gamma-aminobutyric acid (GABA)(A)
      receptors, other mechanisms may be involved. The hyperpolarization-activated
      cation current (I(h)) regulates excitability and rhythmic firing in
      thalamocortical relay neurons in the ventrobasal (VB) complex of the thalamus.
      Here we investigated the effects of propofol on I(h)-related function in vitro
      and in vivo. In whole-cell current-clamp recordings from VB neurons in mouse (P23
      35) brain slices, propofol markedly reduced the voltage sag and low-threshold
      rebound excitation that are characteristic of the activation of I(h). In whole
      cell voltage-clamp recordings, propofol suppressed the I(h) conductance and
      slowed the kinetics of activation. The block of I(h) by propofol was associated
      with decreased regularity and frequency of delta-oscillations in VB neurons. The
      principal source of the I(h) current in these neurons is the hyperpolarization
      activated cyclic nucleotide-gated (HCN) type 2 channel. In human embryonic kidney
      (HEK)293 cells expressing recombinant mouse HCN2 channels, propofol decreased
      I(h) and slowed the rate of channel activation. We also investigated whether
      propofol might have persistent effects on thalamic excitability in the mouse.
      Three hours following an injection of propofol sufficient to produce loss-of
      righting reflex in mice (P35), I(h) was decreased, and this was accompanied by a
      corresponding decrease in HCN2 and HCN4 immunoreactivity in thalamocortical
      neurons in vivo. These results suggest that suppression of I(h) may contribute to
      the inhibition of thalamocortical activity during propofol anesthesia. Longer
      term effects represent a novel form of propofol-mediated regulation of I(h).

PMID- 16420455
TI  - Functional contribution of specific brain areas to absence seizures: role of
      thalamic gap-junctional coupling.
AB  - The synchronized discharges typical of seizures have a multifactorial origin at
      molecular, cellular and network levels. During recent years, the functional role
      of gap-junctional coupling has received increased attention as a mechanism that
      may participate in seizure generation. We have investigated the possible
      functional roles of thalamic and hippocampal gap-junctional communication (GJC)
      in the generation of spike-and-wave discharges in a rodent model of atypical
      absence seizures. Seizures in this model spread throughout limbic, thalamic and
      neocortical areas. Rats were chronically implanted with cannulae to deliver drugs
      or saline, and local field potentials recordings were performed using
      intracerebral electrodes positioned in distinct brain areas. Initially, the
      effects on synaptic transmission of the gap-junctional blockers used in this
      study were determined. Neither carbenoxolone (CBX) nor 18-alpha-glycyrrhetinic
      acid altered chemical synaptic transmission at the concentrations tested. These
      two compounds, when injected via cannulae into the reticular nucleus of the
      thalamus (NRT), decreased significantly the duration of seizures as compared with
      saline injections or injections of the CBX inactive derivative glycyrrhizic acid.
      CBX injections into the hippocampus resulted in diminished seizure activity as
      well. NRT injections of trimethylamine, which presumably causes intracellular
      alkalinization (thereby promoting gap-junctional opening), enhanced seizures and
      spindle activity. These observations suggest that, in this rodent model, thalamic
      and limbic areas are involved in the synchronous paroxysmal activity and that GJC
      contributes to the spike-and-wave discharges.

PMID- 16420456
TI  - Difference in sleep regulation between morning and evening circadian types as
      indexed by antero-posterior analyses of the sleep EEG.
AB  - Circadian types classify individuals according to their preferred timing for
      activity and sleep, morning and evening types showing, respectively, early or
      late preferences. This characteristic has been associated with corresponding
      differences in circadian sleep propensity. In this study, quantitative analysis
      of the sleep EEG in antero-posterior derivations was used to test the hypothesis
      that morning and evening types differ not only in the circadian aspect of sleep
      regulation but also in the homeostatic aspect. Morning types and evening types
      (six men and six women per group, aged 19-34 years) were selected using the
      Morningness-Eveningness Questionnaire. They were studied by polysomnography
      according to their preferred sleep schedule. Spectral activity in four midline
      derivations (Fz, Cz, Pz, Oz) was calculated separately in nonrapid eye movement
      (NREM) sleep and in rapid eye movement (REM) sleep. In NREM sleep, morning types
      showed a steeper decrease of slow-wave activity (SWA; 1-5 Hz) per sleep cycle in
      the fronto-central derivations and a steeper increase in 13-14 Hz activity in the
      parieto-occipital derivations than did evening types. Nonlinear regression
      analysis revealed that the exponential decay rate of relative values of SWA in
      NREM sleep was faster in morning than evening types, in the frontal derivation.
      In REM sleep, morning types showed a steeper decrease of high sigma (14-16 Hz)
      and beta (16-24 Hz) activities across the night in centro-parietal derivations
      than did evening types. These results show for the first time a clear difference
      between morning types and evening types in homeostatic sleep regulation.

PMID- 16420457
TI  - A novel role for calcium-independent phospholipase A in alpha-amino-3-hydroxy-5
      methylisoxazole-propionate receptor regulation during long-term potentiation.
AB  - A considerable body of evidence indicates that phospholipase A(2) (PLA(2))
      enzymes participate in long-term potentiation (LTP) of excitatory synaptic
      transmission. In the present study, we have undertaken experiments to identify
      which calcium-independent isoform of PLA(2) is involved in synaptic plasticity
      and to determine whether calcium-independent PLA(2) (iPLA(2)) contributes to post
      synaptic processes of LTP. Using field recordings from rat CA1 hippocampal
      slices, we found that theta-burst stimulation (TBS)-induced LTP of field
      excitatory post-synaptic potentials (fEPSPs) was abolished by the iPLA(2)
      inhibitor bromoenol lactone (BEL) but not by the Ca(2+)-dependent PLA(2)
      inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3)). The ionic currents
      generated during TBS were not affected during iPLA(2) inhibition as BEL by itself
      had no effect on the magnitude of facilitation during burst responses. In
      addition, (R)-BEL, an enantioselective inhibitor of iPLA(2)gamma, precluded TBS
      induced LTP, an action that was not replicated by the iPLA(2)beta inhibitors (S)
      BEL and methyl arachidonyl fluorophosphonate. (R)-BEL was, however, ineffective
      on pre-established LTP. Finally, BEL also prevented the potentiation of fEPSPs
      elicited by brief exposure to 50 microM N-methyl-d-aspartate, as well as the
      associated up-regulation of alpha-amino-3-hydroxy-5-methylisoxazole-propionate
      (AMPA) receptor GluR1 subunit levels and the increase of (3)H-AMPA binding in
      crude synaptic fractions. Collectively, these results unravel a new role for
      iPLA(2)gamma in LTP, which appears to favor the insertion of AMPA receptors at
      post-synaptic membranes.

PMID- 16420458
TI  - Evidence for a functional role of GABA receptors in the rat mature hippocampus.
AB  - Both gamma-aminobutyric acid (GABA)(C) receptor subunit mRNA and protein are
      expressed in the stratum pyramidale in the CA1 area of the adult rat hippocampus,
      but so far no conclusive evidence about functional hippocampal GABA(C) receptors
      has been presented. Here, the contribution of GABA(C) receptors to stimulus
      evoked postsynaptic potentials was studied in the hippocampal CA1 area with
      extracellular and intracellular recordings at the age range of 21-47 postnatal
      days. Activation of GABA(C) receptors with the specific agonist cis-4
      aminocrotonic acid (CACA) suppressed postsynaptic excitability and increased the
      membrane conductance. The GABA(C) receptor antagonist 1,2,5,6-tetrahydropyridine
      4-ylmethylphosphinic acid (TPMPA), but not the GABA(A) receptor antagonist
      bicuculline, inhibited the effects of CACA. GABA-mediated long-lasting
      depolarizing responses evoked by high-frequency stimulation of local inhibitory
      interneurons in the CA1 area in the presence of ionotropic glutamate receptor and
      GABA(B) receptor blockers were prolonged by TPMPA, indicating that GABA(C)
      receptors are activated under these conditions. For weaker stimulation, the
      effect of TPMPA was enhanced after GABA uptake was inhibited. Our data
      demonstrate that GABA(C) receptors can be activated by endogenous synaptic
      transmitter release following strong stimulation or under conditions of reduced
      GABA uptake. The lack of GABA(C) receptor activation by less intensive
      stimulation under control conditions suggests that these receptors are
      extrasynaptic and activated via spillover of synaptically released GABA.

PMID- 16420460
TI  - Reduced ethanol response in the alcohol-preferring RHA rats and neuropeptide
      mRNAs in relevant structures.
AB  - Roman rat strains, genetically selected for high (RHA) or low (RLA) active
      avoidance acquisition in the two-way shuttle box, differ in dopaminergic
      activity. These two strains appear to be a valid laboratory model of divergent
      sensation/novelty and substance-seeking profiles. RHA rats show higher ethanol
      intake and preference than do RLA rats, and it was suggested that RHA rats are
      more tolerant than RLA to the effects of alcohol. In the hole-board test, we
      found that the non-alcohol-preferring RLA rats showed enhanced responsiveness to
      the stimulatory effects of intraperitoneal administration of 0.25 g/kg ethanol
      when compared with RHA rats. In situ hybridization analysis showed higher levels
      of preprodynorphin in the accumbens shell and higher levels of preproenkephalin
      in the cingulate cortex in RHA rats. RLA rats showed higher levels of enkephalin
      gene transcripts in restricted areas of the dorsal striatum. Finally, differences
      in cholecystokinin gene transcript, suggestive of a different arrangement of
      certain interneurons, were found in different cortical areas. The differences in
      peptide gene expression found between the two strains might reflect the
      differences in alcohol preference and sensitivity. RHA rats may have more
      predictive value than other rodent alcoholism models, as high initial tolerance
      to ethanol is a risk factor for alcoholism in humans.

PMID- 16420459
TI  - The vomeronasal organ is required for the expression of lordosis behaviour, but
      not sex discrimination in female mice.
AB  - The role of the vomeronasal organ (VNO) in mediating neuroendocrine responses in
      female mice is well known; however, whether the VNO is equally important for sex
      discrimination is more controversial as evidence exists for a role of the main
      olfactory system in mate recognition. Therefore, we studied the effect of VNO
      removal (VNOx) on the ability of female mice to discriminate between volatile and
      non-volatile odours of conspecifics of the two sexes and in different endocrine
      states using Y-maze tests. VNOx female mice were able to reliably distinguish
      between male and female or male and gonadectomized (gdx) male volatile odours.
      However, when subjects had to discriminate between male and female or gdx male
      non-volatile odours, VNOx females were no longer able to discriminate between sex
      or different endocrine status. These results thus show that the VNO is primarily
      involved in the detection and processing of non-volatile odours, and that female
      mice can use volatile odours detected and processed by the main olfactory system
      for mate recognition. However, VNO inputs are needed to promote contact with the
      male, including facilitation of lordosis responses to his mounts. A single
      subcutaneous injection with gonadotropin-releasing hormone (GnRH) partially
      reversed the deficit in lordosis behaviour observed in VNOx females suggesting
      that VNO inputs may reach hypothalamic GnRH neurons to influence the display of
      sexual behaviour.

PMID- 16420461
TI  - Prenatal stress: opposite effects on anxiety and hypothalamic expression of
      vasopressin and corticotropin-releasing hormone in rats selectively bred for high
      and low anxiety.
AB  - We studied the mechanisms of genetic-early environmental interactions to modulate
      adult stress-coping and tested the hypothesis that prenatal stress (PS) can
      differentially alter the consequences of a genetic predisposition to either hyper
      or hypo-anxiety. Exposure of male Wistar rats, bred for high (HAB) or low (LAB)
      anxiety-related behaviour, to PS between pregnancy days 4 and 18 resulted in
      opposite effects on anxiety in adulthood, i.e. HAB rats became less and LAB rats
      became more anxious compared with their unstressed controls (plus-maze and
      holeboard). The high anxiety of HAB controls was accompanied by elevated
      expression of vasopressin and corticotropin-releasing hormone (CRH) mRNA within
      the hypothalamic paraventricular nucleus compared with LAB rats. PS reduced CRH
      mRNA expression in HAB rats but increased vasopressin mRNA expression in LAB
      rats, which may explain the opposite effects of PS on adult emotionality.
      Differential effects of PS were also found with respect to hypothalamo-pituitary
      adrenal axis reactivity; the hypothalamo-pituitary-adrenal hyper-response in
      virgin female HAB controls became attenuated after PS, without affecting plasma
      corticosterone concentrations in LAB rats. Differences in maternal plasma
      corticosterone measured between pregnancy days 6 and 14 of HAB and LAB dams or
      differential effects of PS on maternal behaviour can be excluded. In conclusion,
      exposure of rats with genetically determined high or low emotionality to PS
      mitigates the extremes in behavioural and neuroendocrine stress-coping, thus
      allowing adequate and similar behavioural responses to potentially dangerous
      stimuli in adulthood. Differential effects of PS on the activity of the brain
      vasopressin and CRH systems might represent possible underlying molecular
      mechanisms.

PMID- 16420462
TI  - Serotonergic modulation of neuronal responses to behavioural inhibition and
      reinforcing stimuli: an fMRI study in healthy volunteers.
AB  - Serotonin (5-HT) has been implicated in the aetiology of a number of psychiatric
      conditions, including depression, anxiety and antisocial personality disorder.
      The development of these disorders may arise from alterations in underlying
      motivational and cognitive processes such as emotional recognition, reinforcement
      processing and central inhibitory control. This study aimed to localize where in
      the brain 5-HT modulates neuropsychological processes relevant to putative 5-HT
      disorders, using functional magnetic resonance imaging. We examined the effect of
      the antidepressant mirtazapine on brain activations associated with behavioural
      inhibition and reinforcement processing in healthy subjects. Forty-five men were
      randomly allocated to receiving mirtazapine or placebo in a double-blind fashion.
      A Go/No-Go, Reward/No-Reward and Loss/No-loss task were performed during
      functional magnetic resonance imaging using a 1.5 Tesla Philips Gyroscan scanner.
      Blood oxygenation level dependent (BOLD) responses were analysed using SPM2. Task
      activations were largely consistent with previous findings. Mirtazapine modulated
      brain activations in the Go/No-Go and Reward/No-Reward task. During behavioural
      inhibition, enhanced activations were observed in the right orbitofrontal cortex
      (BA47). Increased activations in bilateral parietal cortex were found during the
      Reward task while no significant interaction was observed in the Loss task. Our
      results support the suggestion of an important role of serotonin in modulating
      basic processes involved in psychiatric disorders. Combining drug challenge with
      fMRI (pharmacoMRI; pMRI) is a promising tool for investigating these processes in
      healthy as well as patient groups.

PMID- 16420463
TI  - Sensitivity to optic flow in human cortical areas MT and MST.
AB  - The macaque V5/MT complex comprises several sub-regions but little is known of
      their human homologues. We examined human V5/MT with fMRI in terms of specificity
      to optic flow stimuli, a key characteristic of macaque MST. Stimuli were large
      fields of moving dots, forming coherent global flow patterns. Random motion was
      used as a control. Retinotopic mapping was also conducted. The previously
      suggested existence of at least two distinct sub-regions, MT and MST, within the
      V5/MT complex was confirmed. Human MT is activated about equally by all moving
      dot patterns, including random motion, suggesting that it has little sensitivity
      to global flow structure. As previously described, this region shows strong signs
      of retinotopic organization and is only weakly activated by stimuli confined to
      the ipsilateral hemifield. In human MST, located immediately anterior to MT and
      strongly driven by ipsilateral stimuli, activation varies markedly with optic
      flow structure. The strongest activation is produced by complex flow that
      contains multiple flow components (expansion, contraction and rotation). Single
      components produce rather less response, while rigid translation and random
      motion produce less still. The results suggest that human MST is strongly
      specialized for encoding global flow properties, while human MT is less so.

PMID- 16420464
TI  - Activation of alpha7 acetylcholine receptors augments stimulation-induced
      hippocampal theta oscillation.
AB  - In the septohippocampal formation alpha7 nicotinic receptors (alpha7 nAChRs) are
      predominantly expressed by neurons well positioned to modulate hippocampal theta
      oscillation, such as GABAergic interneurons in the hippocampus, and by both
      GABAergic and cholinergic septal neurons. In the present experiments, we
      evaluated the efficacy of the recently developed selective alpha7 nAChR agonist
      PNU-282987 on hippocampal theta oscillation in anaesthetized rats. This compound
      shows high affinity for the rat alpha7 nAChRs (Ki = 26 nM) but a negligible
      activity at other nAChRs. Systemic administration of PNU-282987 significantly
      enhanced the power (by 40%) of hippocampal theta oscillation induced by
      electrical stimulation of the brainstem reticular formation. In contrast, the
      amnesic and muscarinic receptor antagonist scopolamine significantly decreased
      the power (by 68%) of the stimulation-induced theta oscillation. Given the
      connection between hippocampal theta oscillation and cognitive processes, it is
      proposed that precognitive actions of alpha7 nAChR agonists could be mediated, at
      least in part, by modulation of hippocampal oscillatory activity.

PMID- 16420465
TI  - Plasticity-related regulation of the hippocampal proteome.
AB  - Plasticity of glutamatergic synapses is considered to be a pivotal mechanism
      underlying the ability of the CNS to re-configure its neural circuits. A large
      number of studies have focused on investigating how individual proteins,
      biochemical pathways and structural processes alter both the induction and
      maintenance of synaptic plasticity. However, it is likely that synaptic
      plasticity involves temporally and spatially coordinated regulation of multiple
      protein complexes within the activated neural circuit. By using a global
      proteomics-based approach we have now been able to reveal that highly diverse
      protein classes exhibit altered expression in response to both the activation of
      glutamate receptors and the induction of long-term potentiation (LTP) of
      glutamatergic synaptic strength in the hippocampus; a brain area where plastic
      synaptic modification is believed to be key to cognitive processes, such as
      spatial learning. Of the 2946 resolvable protein spots detected in this study, 79
      (2.7%) were significantly altered in abundance in response to 100 microM
      glutamate application (all P < 0.05). The majority (56 out of 79) of these
      changes were due to the activation of the N-methyl-d-aspartate (NMDA) subtype of
      glutamate receptor. Likewise, the induction of LTP was associated with an altered
      abundance of 2.4% of the detectable proteome during the early (10 min) phase and
      1.7% during the late (4 h) phase of its development. Observed changes in temporal
      and protein class-specific patterns of expression depict a widespread shift from
      metabolic to structural protein alteration as the plasticity process matures.

PMID- 16420466
TI  - Long-term depression of neuron to glial signalling in rat cerebellar cortex.
AB  - Bergmann glial cells enclose synapses throughout the molecular layer of the
      cerebellum and express extrasynaptic AMPA receptors and glutamate transporters.
      Accordingly, stimulation of parallel fibres leads to the generation of inward
      currents in the glia due to AMPA receptor activation and electrogenic uptake of
      glutamate. Elimination of AMPA receptor Ca(2+) permeability leads to the
      withdrawal of glial processes and synaptic dysfunction, suggesting that AMPA
      receptor-mediated Ca(2+) signalling is essential for glial support of the
      neuronal network. Here we show that glial extrasynaptic currents (ESCs) exhibit
      activity-dependent plasticity, specifically, long-term depression during
      repetitive stimulation of parallel fibres at low frequencies (0.033-1 Hz) --
      conditions in which Purkinje neuron excitatory postsynaptic currents (EPSCs)
      remain stable. Both the rate of onset and the magnitude of ESC depression
      increased with stimulation frequency. Depression was reversible following brief
      periods of stimulation, but became increasingly persistent as the duration of
      repetitive stimulation increased. All glial currents -- AMPA receptors, glutamate
      transporter and a recently discovered slow 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo
      benzo[f]quinoxaline-7-sulphonamide (NBQX)-sensitive current -- were depressed.
      Increasing presynaptic release probability by doubling external Ca(2+)
      concentration did not affect the time course of depression, suggesting that
      neither decreased release probability nor fatigue of release sites contribute to
      depression. Inhibition of glutamate uptake caused a dramatic enhancement of the
      rate of depression, implicating glutamate in the underlying mechanism. The
      strength of neuron to glial signalling in the cerebellum is therefore dynamically
      regulated, independently of adjacent synapses, by the frequency of parallel fibre
      activity.

PMID- 16420467
TI  - Sensorineural hearing loss in insulin-like growth factor I-null mice: a new model
      of human deafness.
AB  - It has been reported that mutations in the gene encoding human insulin-like
      growth factor-I (IGF-I) cause syndromic hearing loss. To study the precise role
      of IGF-I in auditory function and to hypothesize the possible morphological and
      electrophysiological changes that may occur in the human inner ear, we have
      analysed the auditory brainstem response in a mouse model of IGF-I deficiency. We
      show here that homozygous Igf-1(-/-) mice present an all-frequency involved
      bilateral sensorineural hearing loss. Igf-1(-/-) mice also present a delayed
      response to acoustic stimuli; this increases along the auditory pathway,
      indicating a contribution of the central nervous system to the hearing loss in
      Igf-1(-/-) mice. These results support the use of the Igf-1(-/-) mouse as a new
      model for the study of human syndromic deafness.

PMID- 16420468
TI  - Visuospatial reorienting signals in the human temporo-parietal junction are
      independent of response selection.
AB  - This study contrasts visuospatial reorienting and response selection signals in
      the right temporo-parietal junction (TPJ) with functional magnetic resonance
      imaging. The overall goal was to investigate whether spatial orienting signals
      and motor signals interacted or were independent in TPJ. The right TPJ showed a
      greater response to targets at in-validly rather than validly cued locations, but
      no significant modulation from the effector used to respond. We suggest that TPJ
      may work as a modality-independent 'circuit breaker' for the dorsal fronto
      parietal attention system, directing attention to salient events and enabling a
      variety of responses to those events.

PMID- 16420469
TI  - Calcium, mitochondria and oxidative stress in neuronal pathology. Novel aspects
      of an enduring theme.
AB  - The interplay among reactive oxygen species (ROS) formation, elevated
      intracellular calcium concentration and mitochondrial demise is a recurring theme
      in research focusing on brain pathology, both for acute and chronic
      neurodegenerative states. However, causality, extent of contribution or the
      sequence of these events prior to cell death is not yet firmly established. Here
      we review the role of the alpha-ketoglutarate dehydrogenase complex as a newly
      identified source of mitochondrial ROS production. Furthermore, based on
      contemporary reports we examine novel concepts as potential mediators of neuronal
      injury connecting mitochondria, increased [Ca2+]c and ROS/reactive nitrogen
      species (RNS) formation; specifically: (a) the possibility that plasmalemmal
      nonselective cationic channels contribute to the latent [Ca2+]c rise in the
      context of glutamate-induced delayed calcium deregulation; (b) the likelihood of
      the involvement of the channels in the phenomenon of 'Ca2+ paradox' that might be
      implicated in ischemia/reperfusion injury; and (c) how ROS/RNS and mitochondrial
      status could influence the activity of these channels leading to loss of ionic
      homeostasis and cell death.

PMID- 16420470
TI  - A spectroscopic study of the interaction of isoflavones with human serum albumin.
AB  - Genistein and daidzein, the major isoflavones present in soybeans, possess a wide
      spectrum of physiological and pharmacological functions. The binding of genistein
      to human serum albumin (HSA) has been investigated by equilibrium dialysis,
      fluorescence measurements, CD and molecular visualization. One mole of genistein
      is bound per mole of HSA with a binding constant of 1.5 +/- 0.2 x 10(5) m(-1).
      Binding of genistein to HSA precludes the attachment of daidzein. The ability of
      HSA to bind genistein is found to be lost when the tryptophan residue of albumin
      is modified with N-bromosuccinimide. At 27 degrees C (pH 7.4), van't Hoff's
      enthalpy, entropy and free energy changes that accompany the binding are found to
      be -13.16 kcal x mol(-1), -21 cal x mol(-1) K(-1) and -6.86 kcal x mol(-1),
      respectively. Temperature and ionic strength dependence and competitive binding
      measurements of genistein with HSA in the presence of fatty acids and 8-anilino-1
      naphthalene sulfonic acid have suggested the involvement of both hydrophobic and
      ionic interactions in the genistein-HSA binding. Binding measurements of
      genistein with BSA and HSA, and those in the presence of warfarin and 2,3,5-tri
      iodobenzoic acid and Forster energy transfer measurements have been used for
      deducing the binding pocket on HSA. Fluorescence anisotropy measurements of
      daidzein bound and then displaced with warfarin, 2,3,5-tri-iodobenzoic acid or
      diazepam confirm the binding of daidzein and genistein to subdomain IIA of HSA.
      The ability of HSA to form ternery complexes with other neutral molecules such as
      warfarin, which also binds within the subdomain IIA pocket, increases our
      understanding of the binding dynamics of exogenous drugs to HSA.

PMID- 16420471
TI  - The hemoglobin genes of Drosophila.
AB  - We recently reported the unprecedented occurrence of a hemoglobin gene (glob1) in
      the fruitfly Drosophila melanogaster. Here we investigate the structure and
      evolution of the glob1 gene in other Drosophila species. We cloned and sequenced
      glob1 genes and cDNA from D. pseudoobscura and D. virilis, and identified the
      glob1 gene sequences of D. simulans, D. yakuba, D. erecta, D. ananassae, D.
      mojavensis and D. grimshawi in the databases. Gene structure (introns in helix
      positions D7.0 and G7.0), gene synteny and sequence of glob1 are highly
      conserved, with high ds/dn ratios indicating strong purifying selection. The data
      suggest an important role of the glob1 protein in Drosophila, which may be the
      control of oxygen flow from the tracheal system. Furthermore, we identified two
      additional globin genes (glob2 and glob3) in the Drosophilidae. Although the
      sequences are highly derived, the amino acids required for heme- and oxygen
      binding are conserved. In contrast to other known insect globin, the glob2 and
      glob3 genes harbour both globin-typical introns at positions B12.2 and G7.0. Both
      genes are conserved in various drosophilid species, but only expression of glob2
      could be demonstrated by western blotting and RT-PCR. Phylogenetic analyses show
      that the clade leading to glob2 and glob3, which are sistergroups, diverged first
      in the evolution of dipteran globins. glob1 is closely related to the
      intracellular hemoglobin of the botfly Gasterophilus intestinalis, and the
      extracellular hemoglobins from the chironomid midges derive from this clade.

PMID- 16420473
TI  - Endo/exo mechanism and processivity of family 18 chitinases produced by Serratia
      marcescens.
AB  - We present a comparative study of ChiA, ChiB, and ChiC, the three family 18
      chitinases produced by Serratia marcescens. All three enzymes eventually
      converted chitin to N-acetylglucosamine dimers (GlcNAc2) and a minor fraction of
      monomers. ChiC differed from ChiA and ChiB in that it initially produced longer
      oligosaccharides from chitin and had lower activity towards an oligomeric
      substrate, GlcNAc6. ChiA and ChiB could convert GlcNAc6 directly to three dimers,
      whereas ChiC produced equal amounts of tetramers and dimers, suggesting that the
      former two enzymes can act processively. Further insight was obtained by studying
      degradation of the soluble, partly deacetylated chitin-derivative chitosan.
      Because there exist nonproductive binding modes for this substrate, it was
      possible to discriminate between independent binding events and processive
      binding events. In reactions with ChiA and ChiB the polymer disappeared very
      slowly, while the initially produced oligomers almost exclusively had even
      numbered chain lengths in the 2-12 range. This demonstrates a processive mode of
      action in which the substrate chain moves by two sugar units at a time,
      regardless of whether complexes formed along the way are productive. In contrast,
      reactions with ChiC showed rapid disappearance of the polymer and production of a
      continuum of odd- and even-numbered oligomers. These results are discussed in the
      light of recent literature data on directionality and synergistic effects of
      ChiA, ChiB and ChiC, leading to the conclusion that ChiA and ChiB are processive
      chitinases that degrade chitin chains in opposite directions, while ChiC is a
      nonprocessive endochitinase.

PMID- 16420472
TI  - Gene duplication and separation of functions in alphaB-crystallin from zebrafish
      (Danio rerio).
AB  - We previously reported that zebrafish alphaB-crystallin is not constitutively
      expressed in nervous or muscular tissue and has reduced chaperone-like activity
      compared with its human ortholog. Here we characterize the tissue expression
      pattern and chaperone-like activity of a second zebrafish alphaB-crystallin.
      Expressed sequence tag analysis of adult zebrafish lens revealed the presence of
      a novel alpha-crystallin transcript designated cryab2 and the resulting protein
      alphaB2-crystallin. The deduced protein sequence was 58.2% and 50.3% identical
      with human alphaB-crystallin and zebrafish alphaB1-crystallin, respectively. RT
      PCR showed that alphaB2-crystallin is expressed predominantly in lens but,
      reminiscent of mammalian alphaB-crystallin, also has lower constitutive
      expression in heart, brain, skeletal muscle and liver. The chaperone-like
      activity of purified recombinant alphaB2 protein was assayed by measuring its
      ability to prevent the chemically induced aggregation of alpha-lactalbumin and
      lysozyme. At 25 degrees C and 30 degrees C, zebrafish alphaB2 showed greater
      chaperone-like activity than human alphaB-crystallin, and at 35 degrees C and 40
      degrees C, the human protein provided greater protection against aggregation. 2D
      gel electrophoresis indicated that alphaB2-crystallin makes up approximately
      0.16% of total zebrafish lens protein. Zebrafish is the first species known to
      express two different alphaB-crystallins. Differences in primary structure,
      expression and chaperone-like activity suggest that the two zebrafish alphaB
      crystallins perform divergent physiological roles. After gene duplication,
      zebrafish alphaB2 maintained the widespread protective role also found in
      mammalian alphaB-crystallin, while zebrafish alphaB1 adopted a more restricted,
      nonchaperone role in the lens. Gene duplication may have allowed these functions
      to separate, providing a unique model for studying structure-function
      relationships and the regulation of tissue-specific expression patterns.

PMID- 16420474
TI  - Tryptophan 243 affects interprotein contacts, cofactor binding and stability in D
      amino acid oxidase from Rhodotorula gracilis.
AB  - The flavoenzyme d-amino acid oxidase from Rhodotorula gracilis is a homodimeric
      protein whose dimeric state has been proposed to occur as a result of (a) the
      electrostatic interactions between positively charged residues of the betaF5
      betaF6 loop of one monomer and negatively charged residues belonging to the alpha
      helices I3' and I3'' of the other monomer, and (b) the interaction of residues
      (e.g. Trp243) belonging to the two monomers at the mixed interface region. The
      role of Trp243 was investigated by substituting it with either tyrosine or
      isoleucine: both substitutions were nondisruptive, as confirmed by the absence of
      significant changes in catalytic activity, but altered the tertiary structure
      (yielding a looser conformation) and decreased the stability towards temperature
      and denaturants. The change in conformation interferes both with the interaction
      of the coenzyme to the apoprotein moiety (although the kinetics of the apoprotein
      FAD complex reconstitution process are similar between wild-type and mutant D
      amino acid oxidases) and with the interaction between monomers. Our results
      indicate that, in the folded holoenzyme, Trp243 is situated at a position optimal
      for increasing the interactions between monomers by maximizing van der Waals
      interactions and by efficiently excluding solvent.

PMID- 16420475
TI  - Binding of the viral immunogenic octapeptide VSV8 to native glucose-regulated
      protein Grp94 (gp96) and its inhibition by the physiological ligands ATP and
      Ca2+.
AB  - The molecular chaperone Grp94 (gp96) of the endoplasmic reticulum (ER) lumen
      plays an essential role in the structural maturation and/or secretion of proteins
      destined for transport to the cell surface. Its proposed role in binding and
      transferring peptides for immune recognition is, however, controversial. Using
      SPR spectroscopy, we studied the interaction of native glycosylated Grp94 at
      neutral pH and 25 and 37 degrees C with the viral immunogenic octapeptide
      RGYVYQGL (VSV8), derived from vesicular stomatitis virus nucleoprotein (52-59).
      The peptide binds reversibly with low affinity ([A]0.5 approximately 640 microM)
      and a hyperbolic binding isotherm, and the binding is partially inhibited by ATP
      and Ca2+ at concentrations that are present in the ER lumen, and the effects are
      explained by conformational changes in the native chaperone induced by these
      ligands. Our data present experimental support for the recent proposal that,
      under native conditions, VSV8 binds to Grp94 by an adsorptive, rather than a
      bioselective, mechanism, and thus further challenge the proposed in vivo peptide
      acceptor-donor function of the chaperone in the context of antigen-presenting
      cell activation.

PMID- 16420476
TI  - Comparative metal binding and genomic analysis of the avian (chicken) and
      mammalian metallothionein.
AB  - Chicken metallothionein (ckMT) is the paradigm for the study of metallothioneins
      (MTs) in the Aves class of vertebrates. Available literature data depict ckMT as
      a one-copy gene, encoding an MT protein highly similar to mammalian MT1. In
      contrast, the MT system in mammals consists of a four-member family exhibiting
      functional differentiation. This scenario prompted us to analyse the apparently
      distinct evolutionary patterns followed by MTs in birds and mammals, at both the
      functional and structural levels. Thus, in this work, the ckMT metal binding
      abilities towards Zn(II), Cd(II) and Cu(I) have been thoroughly revisited and
      then compared with those of the mammalian MT1 and MT4 isoforms, identified as
      zinc- and copper-thioneins, respectively. Interestingly, a new mechanism of MT
      dimerization is reported, on the basis of the coordinating capacity of the ckMT C
      terminal histidine. Furthermore, an evolutionary study has been performed by
      means of in silico analyses of avian MT genes and proteins. The joint
      consideration of the functional and genomic data obtained questions the two
      features until now defining the avian MT system. Overall, in vivo and in vitro
      metal-binding results reveal that the Zn(II), Cd(II) and Cu(I) binding abilities
      of ckMT lay between those of mammalian MT1 and MT4, being closer to those of MT1
      for the divalent metal ions but more similar to those of MT4 for Cu(I). This is
      consistent with a strong functional constraint operating on low-copy number genes
      that must cope with differentiating functional limitation. Finally, a second MT
      gene has been identified in silico in the chicken genome, ckMT2, exhibiting all
      the features to be considered an active coding region. The results presented here
      allow a new insight into the metal binding abilities of warm blooded vertebrate
      MTs and their evolutionary relationships.

PMID- 16420477
TI  - Secretion of proteases in serglycin transfected Madin-Darby canine kidney cells.
AB  - Madin-Darby canine kidney (MDCK) cells, which do not normally express the
      proteoglycan (PG) serglycin, were stably transfected with cDNA for human
      serglycin fused to a polyhistidine tag (His-tag). Clones with different levels of
      serglycin mRNA expression were generated. One clone with lower and one with
      higher serglycin mRNA expression were selected for this study. 35S-labelled
      serglycin in cell fractions and conditioned media was isolated using HisTrap
      affinity chromatography. Serglycin could also be detected in conditioned media
      using western blotting. To investigate the possible importance of serglycin
      linked to protease secretion, enzyme activities using chromogenic substrates and
      zymography were measured in cell fractions and serum-free conditioned media of
      the different clones. Cells were cultured in both the absence and presence of
      phorbol 12-myristate 13-acetate (PMA). In general, enzyme secretion was strongly
      enhanced by treatment with PMA. Our analyses revealed that the clone with the
      highest serglycin mRNA expression, level of HisTrap isolated 35S-labelled
      serglycin, and amount of serglycin core protein as detected by western blotting,
      also showed the highest secretion of proteases. Transfection of serglycin into
      MDCK cells clearly leads to changes in secretion levels of secreted endogenous
      proteases, and could provide further insight into the biosynthesis and secretion
      of serglycin and potential partner molecules.

PMID- 16420478
TI  - Cholesterol and its anionic derivatives inhibit 5-lipoxygenase activation in
      polymorphonuclear leukocytes and MonoMac6 cells.
AB  - 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes
      (LTs), biological mediators of host defense reactions and of inflammatory
      diseases. While the role of membrane binding in the regulation of 5-LO activity
      is well established, the effects of lipids on cellular activity when added to the
      medium has not been characterized. Here, we show such a novel function of the
      most abundant sulfated sterol in human blood, cholesterol sulfate (CS), to
      suppress LT production in human polymorphonuclear leukocytes (PMNL) and Mono Mac6
      cells. We synthesized another anionic lipid, cholesterol phosphate, which
      demonstrated a similar capacity in suppression of LT synthesis in PMNL.
      Cholesteryl acetate was without effect. Cholesterol increased the effect of CS on
      5-LO product synthesis. CS and cholesterol also inhibited arachidonic acid (AA)
      release from PMNL. Addition of exogenous AA increased the threshold concentration
      of CS required to inhibit LT synthesis. The effect of cholesterol and its anionic
      derivatives can arise from remodeling of the cell membrane, which interferes with
      5-LO activation. The fact that cellular LT production is regulated by sulfated
      cholesterol highlights a possible regulatory role of sulfotransferases/sulfatases
      in 5-LO product synthesis.

PMID- 16420479
TI  - Replacement of helix 1' enhances the lipid binding activity of apoE3 N-terminal
      domain.
AB  - The N-terminal domain of human apolipoprotein E (apoE-NT) harbors residues
      critical for interaction with members of the low-density lipoprotein receptor
      (LDLR) family. Whereas lipid free apoE-NT adopts a stable four-helix bundle
      conformation, a lipid binding induced conformational adaptation is required for
      manifestation of LDLR binding ability. To investigate the structural basis for
      this conformational change, the short helix connecting helix 1 and 2 in the four
      helix bundle was replaced by the sequence NPNG, introducing a beta-turn.
      Recombinant helix-to-turn (HT) variant apoE3-NT was produced in Escherichia coli,
      isolated and characterized. Stability studies revealed a denaturation transition
      midpoint of 1.9 m guanidine hydrochloride for HT apoE3-NT vs. 2.5 M for wild-type
      apoE3-NT. Wild-type and HT apoE3-NT form dimers in solution via an intermolecular
      disulfide bond. Native PAGE showed that reconstituted high-density lipoprotein
      prepared with HT apoE3-NT have a diameter in the range of 9 nm and possess
      binding activity for the LDLR on cultured human skin fibroblasts. In phospholipid
      vesicle solubilization assays, HT apoE3-NT was more effective than wild-type
      apoE3-NT at inducing a time dependent decrease in dimyristoylphosphatidylglycerol
      vesicle light scattering intensity. In lipoprotein binding assays, HT apoE3-NT
      protected human low-density lipoprotein from phospholipase C induced aggregation
      to a greater extent that wild-type apoE3-NT. The results indicate that a mutation
      at one end of the apoE3-NT four-helix bundle markedly enhances the lipid binding
      activity of this protein. In the context of lipoprotein associated full-length
      apoE, increased lipid binding affinity of the N-terminal domain may alter the
      balance between receptor-active and -inactive conformational states.

PMID- 16420480
TI  - Prohibitin attenuates insulin-stimulated glucose and fatty acid oxidation in
      adipose tissue by inhibition of pyruvate carboxylase.
AB  - Prohibitin (PHB-1) is a highly conserved protein involved in mitochondrial
      biogenesis and function. It is secreted in lipid droplets from adipocytes and is
      present in the circulation. In adipose tissue it functions as a membrane receptor
      and can target binding partners to the mitochondria. Here we report that PHB-1
      has a hitherto undescribed role as an inhibitor of pyruvate carboxylase (PC). As
      a consequence, it can modulate insulin-stimulated glucose and fatty acid
      oxidation. It had no effect on insulin-stimulated 2-deoxglucose uptake by
      isolated adipocytes but inhibited insulin-stimulated oxidation of [14C]glucose
      with a half-maximal concentration of approximately 4 nM. It also inhibited oleic
      acid oxidation in glucose-depleted adipocytes via depletion of oxaloacetate. In
      vitro experiments using broken-cell assays confirmed that PHB-1 inhibited PC.
      MALDI-TOF analysis of proteins identified by cross-linking of PHB-1 to adipocyte
      membranes indicated that PHB-1 is closely associated with PC and EH domain 2
      (EHD2). On the basis of these data, we propose that PHB-1 is recycled between the
      extracellular space and the mitochondria by a mechanism involving lipid rafts and
      EHD2 and can modulate mitochondrial fuel metabolism by inhibition of PC.

PMID- 16420481
TI  - Major phosphorylation of SF1 on adjacent Ser-Pro motifs enhances interaction with
      U2AF65.
AB  - Protein phosphorylation ensures the accurate and controlled expression of the
      genome, for instance by regulating the activities of pre-mRNA splicing factors.
      Here we report that splicing factor 1 (SF1), which is involved in an early step
      of intronic sequence recognition, is highly phosphorylated in mammalian cells on
      two serines within an SPSP motif at the junction between its U2AF65 and RNA
      binding domains. We show that SF1 interacts in vitro with the protein kinase KIS,
      which possesses a 'U2AF homology motif' (UHM) domain. The UHM domain of KIS is
      required for KIS and SF1 to interact, and for KIS to efficiently phosphorylate
      SF1 on the SPSP motif. Importantly, SPSP phosphorylation by KIS increases binding
      of SF1 to U2AF65, and enhances formation of the ternary SF1-U2AF65-RNA complex.
      These results further suggest that this phosphorylation event has an important
      role for the function of SF1, and possibly for the structural rearrangements
      associated with spliceosome assembly and function.

PMID- 16420482
TI  - Thermal unfolding of smooth muscle and nonmuscle tropomyosin alpha-homodimers
      with alternatively spliced exons.
AB  - We used differential scanning calorimetry (DSC) and circular dichroism (CD) to
      investigate thermal unfolding of recombinant fibroblast isoforms of alpha
      tropomyosin (Tm) in comparison with that of smooth muscle Tm. These two nonmuscle
      Tm isoforms 5a and 5b differ internally only by exons 6b/6a, and they both differ
      from smooth muscle Tm by the N-terminal exon 1b which replaces the muscle
      specific exons 1a and 2a. We show that the presence of exon 1b dramatically
      decreases the measurable calorimetric enthalpy of the thermal unfolding of Tm
      observed with DSC, although it has no influence on the alpha-helix content of Tm
      or on the end-to-end interaction between Tm dimers. The results suggest that a
      significant part of the molecule of fibroblast Tm (but not smooth muscle Tm)
      unfolds noncooperatively, with the enthalpy no longer visible in the cooperative
      thermal transitions measured. On the other hand, both DSC and CD studies show
      that replacement of muscle exons 1a and 2a by nonmuscle exon 1b not only
      increases the thermal stability of the N-terminal part of Tm, but also
      significantly stabilizes Tm by shifting the major thermal transition of Tm to
      higher temperature. Replacement of exon 6b by exon 6a leads to additional
      increase in the alpha-Tm thermal stability. Thus, our data show for the first
      time a significant difference in the thermal unfolding between muscle and
      nonmuscle alpha-Tm isoforms, and indicate that replacement of alternatively
      spliced exons alters the stability of the entire Tm molecule.

PMID- 16420483
TI  - Solution NMR structure of an immunodominant epitope of myelin basic protein.
      Conformational dependence on environment of an intrinsically unstructured
      protein.
AB  - Using solution NMR spectroscopy, three-dimensional structures have been obtained
      for an 18-residue synthetic polypeptide fragment of 18.5 kDa myelin basic protein
      (MBP, human residues Q81-T98) under three conditions emulating the protein's
      natural environment in the myelin membrane to varying degrees: (a) an aqueous
      solution (100 mM KCl pH 6.5), (b) a mixture of trifluoroethanol (TFE-d2) and
      water (30 : 70% v/v), and (c) a dispersion of 100 mM dodecylphosphocholine (DPC
      d38, 1 : 100 protein/lipid molar ratio) micelles. This polypeptide sequence is
      highly conserved in MBP from mammals, amphibians, and birds, and comprises a
      major immunodominant epitope (human residues N83-T92) in the autoimmune disease
      multiple sclerosis. In the polypeptide fragment, this epitope forms a stable,
      amphipathic, alpha helix under organic and membrane-mimetic conditions, but has
      only a partially helical conformation in aqueous solution. These results are
      consistent with recent molecular dynamics simulations that showed this segment to
      have a propensity to form a transient alpha helix in aqueous solution, and with
      electron paramagnetic resonance (EPR) experiments that suggested a alpha-helical
      structure when bound to a membrane [I. R. Bates, J. B. Feix, J. M. Boggs & G.
      Harauz (2004) J Biol Chem, 279, 5757-5764]. The high sensitivity of the epitope
      structure to its environment is characteristic of intrinsically unstructured
      proteins, like MBP, and reflects its association with diverse ligands such as
      lipids and other proteins.

PMID- 16420484
TI  - Identification of membrane-bound serine proteinase matriptase as processing
      enzyme of insulin-like growth factor binding protein-related protein-1 (IGFBP
      rP1/angiomodulin/mac25).
AB  - Insulin-like growth factor (IGF) binding protein-related protein-1 (IGFBP-rP1)
      modulates cellular adhesion and growth in an IGF/insulin-dependent or independent
      manner. It also shows tumor-suppressive activity in vivo. We recently found that
      a single-chain IGFB-rP1 is proteolytically cleaved to a two-chain form by a
      trypsin-like, endogenous serine proteinase, changing its biological activities.
      In this study, we attempted to identify the IGFBP-rP1-processing enzyme. Of nine
      human cell lines tested, seven cell lines secreted IGFBP-rP1 at high levels, and
      two of them, ovarian clear cell adenocarcinoma (OVISE) and gastric carcinoma (MKN
      45), highly produced the cleaved IGFBP-rP1. Serine proteinase inhibitors
      effectively blocked the IGFBP-rP1 cleavage in the OVISE cell culture. The
      conditioned medium of OVISE cells did not cleave purified IGFBP-rP1, but their
      membrane fraction had an IGFBP-rP1-cleaving activity. The membrane fraction
      contained an 80-kDa gelatinolytic enzyme, which was identified as the membrane
      type serine proteinase matriptase (MT-SP1) by immunoblotting. When the membrane
      fraction was separated by SDS/PAGE, the IGFBP-rP1-cleaving activity comigrated
      with matriptase. A soluble form of matriptase purified in an inhibitor-free form
      efficiently cleaved IGFBP-rP1 at the same site as that found in a naturally
      cleaved IGFBP-rP1. Furthermore, small interfering RNAs for matriptase efficiently
      blocked both the matriptase expression and the cleavage of IGBP-rP1 in OVISE
      cells. These results demonstrate that IGFBP-rP1 is processed to the two-chain
      form by matriptase on the cell surface.

PMID- 16420485
TI  - Modulation of oat arginine decarboxylase gene expression and genome organization
      in transgenic Trypanosoma cruzi epimastigotes.
AB  - We have previously demonstrated that wild-type Trypanosoma cruzi epimastigotes
      lack arginine decarboxylase (ADC) enzymatic activity as well as its encoding
      gene. A foreign ADC has recently been expressed in T. cruzi after transformation
      with a recombinant plasmid containing the complete coding region of the oat ADC
      gene. In the present study, upon modulation of exogenous ADC expression, we found
      that ADC activity was detected early after transfection; subsequently it
      decreased to negligible levels between 2 and 3 weeks after electroporation and
      was again detected approximately 4 weeks after electroporation. After this
      period, the ADC activity increased markedly and became expressed permanently.
      These changes of enzymatic activity showed a close correlation with the
      corresponding levels of ADC transcripts. To investigate whether the genome
      organization of the transgenic T. cruzi underwent any modification related to the
      expression of the heterologous gene, we performed PCR amplification assays,
      restriction mapping and pulse-field gel electrophoresis with DNA samples or
      chromosomes obtained from parasites collected at different time-points after
      transfection. The results indicated that the transforming plasmid remained as
      free episomes during the transient expression of the foreign gene. Afterwards,
      the free plasmid disappeared almost completely for several weeks and, finally,
      when the expression of the ADC gene became stable, two or more copies of the
      transforming plasmid arranged in tandem were integrated into a parasite
      chromosome (1.4 Mbp) bearing a ribosomal RNA locus. The sensitivity of
      transcription to alpha-amanitin strongly suggests involvement of the protozoan
      RNA polymerase I in the transcription of the exogenous ADC gene.

PMID- 16420487
TI  - Manipulation of prenyl chain length determination mechanism of cis
      prenyltransferases.
AB  - The carbon backbones of Z,E-mixed isoprenoids are synthesized by sequential cis
      condensation of isopentenyl diphosphate (IPP) and an allylic diphosphate through
      actions of a series of enzymes called cis-prenyltransferases. Recent molecular
      analyses of Micrococcus luteus B-P 26 undecaprenyl diphosphate (UPP, C55)
      synthase [Fujihashi M, Zhang Y-W, Higuchi Y, Li X-Y, Koyama T & Miki K (2001)
      Proc Natl Acad Sci USA98, 4337-4342.] showed that not only the primary structure
      but also the crystal structure of cis-prenyltransferases were totally different
      from those of trans-prenyltransferases. Although many studies on structure
      function relationships of cis-prenyltransferases have been reported, regulation
      mechanisms for the ultimate prenyl chain length have not yet been elucidated. We
      report here that the ultimate chain length of prenyl products can be controlled
      through structural manipulation of UPP synthase of M. luteus B-P 26, based on
      comparisons between structures of various cis-prenyltransferases. Replacements of
      Ala72, Phe73, and Trp78, which are located in the proximity of the substrate
      binding site, with Leu--as in Z,E-farnesyl diphosphate (C15) synthase--resulted
      in shorter ultimate products with C(20-35). Additional mutation of F223H resulted
      in even shorter products. On the other hand, insertion of charged residues
      originating from long-chain cis-prenyltransferases into helix-3, which
      participates in constitution of the large hydrophobic cleft, resulted in
      lengthening of the ultimate product chain length, leading to C(60-75). These
      results helped us understand reaction mechanisms of cis-prenyltransferase
      including regulation of the ultimate prenyl chain-length.

PMID- 16420486
TI  - Delineation of exoenzyme S residues that mediate the interaction with 14-3-3 and
      its biological activity.
AB  - 14-3-3 proteins belong to a family of conserved molecules expressed in all
      eukaryotic cells, which play an important role in a multitude of signaling
      pathways. 14-3-3 proteins bind to phosphoserine/phosphothreonine motifs in a
      sequence-specific manner. More than 200 14-3-3 binding partners have been found
      that are involved in cell cycle regulation, apoptosis, stress responses, cell
      metabolism and malignant transformation. A phosphorylation-independent
      interaction has been reported to occur between 14-3-3 and a C-terminal domain
      within exoenzyme S (ExoS), a bacterial ADP-ribosyltransferase toxin from
      Pseudomonas aeruginosa. In this study, we have investigated the effect of amino
      acid mutations in this C-terminal domain of ExoS on ADP-ribosyltransferase
      activity and the 14-3-3 interaction. Our results suggest that leucine-428 of ExoS
      is the most critical residue for ExoS enzymatic activity, as cytotoxicity
      analysis reveals that substitution of this leucine significantly weakens the
      ability of ExoS to mediate cell death. Leucine-428 is also required for the
      ability of ExoS to modify the eukaryotic endogenous target Ras. Finally, single
      amino acid substitutions of positions 426-428 reduce the interaction potential of
      14-3-3 with ExoS in vitro.

PMID- 16420491
TI  - Deadly household pollution: a call to action.

PMID- 16420488
TI  - Mutagenesis of the central hydrophobic cluster in Abeta42 Alzheimer's peptide.
      Side-chain properties correlate with aggregation propensities.
AB  - Protein misfolding and deposition underlie an increasing number of debilitating
      human disorders. Alzheimer's disease is pathologically characterized by the
      presence of numerous insoluble amyloid plaques in the brain, composed primarily
      of the 42 amino acid human beta-amyloid peptide (Abeta42). Disease-linked
      mutations in Abeta42 occur in or near a central hydrophobic cluster comprising
      residues 17-21. We exploited the ability of green fluorescent protein to act as a
      reporter of the aggregation of upstream fused Abeta42 variants to characterize
      the effects of a large set of single-point mutations at the central position of
      this hydrophobic sequence as well as substitutions linked to early onset of the
      disease located in or close to this region. The aggregational properties of the
      different protein variants clearly correlated with changes in the intrinsic
      physicochemical properties of the side chains at the point of mutation. Reduction
      in hydrophobicity and beta-sheet propensity resulted in an increase of in vivo
      fluorescence indicating disruption of aggregation, as confirmed by the in vitro
      analysis of synthetic Abeta42 variants. The results confirm the key role played
      by the central hydrophobic stretch on Abeta42 deposition and support the
      hypothesis that sequence tunes the aggregation propensities of polypeptides.

PMID- 16420492
TI  - Guest editorial.

PMID- 16420493
TI  - Organic compounds in office environments - sensory irritation, odor, measurements
      and the role of reactive chemistry.
AB  - Abstract Sensory irritation and odor effects of organic compounds in indoor
      environments are reviewed. It is proposed to subdivide volatile organic compounds
      (VOCs) into four categories: (i) chemically non-reactive, (ii) chemically
      'reactive', (iii) biologically reactive (i.e. form chemical bonds to receptor
      sites in mucous membranes) and (iv) toxic compounds. Chemically non-reactive VOCs
      are considered non-irritants at typical indoor air levels. However, compounds
      with low odor thresholds contribute to the overall perception of the indoor air
      quality. Reported sensory irritation may be the result of odor annoyance. It
      appears that odor thresholds for many VOCs probably are considerably lower than
      previously reported. This explains why many building materials persistently are
      perceived as odorous, although the concentrations of the detected organic
      compounds are close to or below their reported odor thresholds. Ozone reacts with
      certain alkenes to form a gas and aerosol phase of oxidation products, some of
      which are sensory irritants. However, all of the sensory irritating species have
      not yet been identified and whether the secondary aerosols (ultrafine and fine
      particles) contribute to sensory irritation requires investigation. Low relative
      humidity may exacerbate the sensory irritation impact. Practical Implications
      Certain odors, in addition to odor annoyance, may result in psychological effects
      and distraction from work. Some building materials continually cause perceivable
      odors, because the odor thresholds of the emitted compounds are low. Some
      oxidation products of alkenes (e.g. terpenes) may contribute to eye and airway
      symptoms under certain conditions and low relative humidity.

PMID- 16420494
TI  - Dust sampling methods for endotoxin - an essential, but underestimated issue.
AB  - Exposure to farming environment in early life has been associated with lower risk
      for allergic diseases possibly caused by increased exposure to endotoxin. The
      aims of this study were to compare the reproducibility of different sampling
      methods for endotoxin, and to determine whether environmental characteristics
      have different effect on endotoxin levels of different sample types. The
      reproducibility of sampling methods (bed dust, floor dust, vacuum cleaner dust
      bag dust, settled dust and air samples) was studied with repeated sampling (five
      visits during 1 year) in five farming and five urban homes. To examine
      determinants of endotoxin for different types of dust sample, sampling was
      conducted once in 12 farming and 17 urban homes. Endotoxin was analyzed using
      Limulus Amebocyte Lysate assay. Bed dust samples had the best reproducibility
      (intraclass correlation, ICC=66%), but the difference between farming and non
      farming homes was not clear with this sample type. The reproducibility of floor
      (ICC=52%) and settled dust (ICC=51%) was moderate. With these sample types the
      difference between farming and non-farming homes was clear. Settled dust had some
      seasonal variation. Based on this study, the best compromise for sampling for
      endotoxin appears to be floor dust sample followed by bed and settled dust
      samples. Practical Implications Endotoxins have been widely measured, even though
      the validity of different sample types to reflect the endotoxin exposure level of
      an indoor environment is poorly known. This study shows that bed dust samples
      have the best reproducibility, but they do not reflect the differences in
      exposure due to environmental factors such as farming. Floor dust samples with
      moderate reproducibility may be the best choice for sampling of endotoxin in
      large field studies.

PMID- 16420495
TI  - Ventilation and performance in office work.
AB  - Outdoor air ventilation rates vary considerably between and within buildings, and
      may be too low in some spaces. The purpose of this study was to evaluate the
      potential work performance benefits of increased ventilation. We analyzed the
      literature relating work performance with ventilation rate and employed
      statistical analyses with weighting factors to combine the results of different
      studies. The studies included in the review assessed performance of various tasks
      in laboratory experiments and measured performance at work in real buildings.
      Almost all studies found increases in performance with higher ventilation rates.
      The studies indicated typically a 1-3% improvement in average performance per 10
      l/s-person increase in outdoor air ventilation rate. The performance increase per
      unit increase in ventilation was bigger with ventilation rates below 20 l/s
      person and almost negligible with ventilation rates over 45 l/s-person. The
      performance increase was statistically significant with increased ventilation
      rates up to 15 l/s-person with 95% CI and up to 17 l/s-person with 90% CI.
      Practical Implications We have demonstrated a quantitative relationship between
      work performance and ventilation within a wide range of ventilation rates. The
      model shows a continuous increase in performance per unit increase in ventilation
      rate from 6.5 l/s-person to 65 l/s-person. The increase is statistically
      significant up to 15 l/s-person. This relationship has a high level of
      uncertainty; however, use of this relationship in ventilation design and
      feasibility studies may be preferable to the current practice, which ignores the
      relationship between ventilation and productivity.

PMID- 16420496
TI  - Relationship between indoor and outdoor bio-aerosols collected with a button
      inhalable aerosol sampler in urban homes.
AB  - This field study investigated the relationship between indoor and outdoor
      concentrations of airborne actinomycetes, fungal spores, and pollen. Air samples
      were collected for 24 h with a button inhalable aerosol sampler inside and
      outside of six single-family homes located in the Cincinnati area (overall, 15
      pairs of samples were taken in each home). The measurements were conducted during
      three seasons - spring and fall 2004, and winter 2005. The concentration of
      culturable actinomycetes was mostly below the detection limit. The median
      indoor/outdoor ratio (I/O) for actinomycetes was the highest: 2.857. The indoor
      of fungal and pollen concentrations followed the outdoor concentrations while
      indoor levels were mostly lower than the outdoor ones. The I/O ratio of total
      fungal spores (median=0.345) in six homes was greater than that of pollen grains
      (median=0.025). The low I/O ratios obtained for pollen during the peak ambient
      pollination season (spring) suggest that only a small fraction penetrated from
      outdoor to indoor environment. This is attributed to the larger size of pollen
      grains. Higher indoor concentration levels and variability in the I/O ratio
      observed for airborne fungi may be associated with indoor sources and/or higher
      outdoor-to-indoor penetration of fungal spores compared to pollen grains.
      Practical Implication This study addresses the relationship between indoor and
      outdoor concentrations of three different types of bio-aerosols, namely
      actinomycetes, fungal spores, and pollen grains. The results show that
      actinomycetes are rare in indoor and outdoor air in Midwest, USA. Exposure to
      pollen occurs mainly in the outdoor air even during peak pollen season.
      Unexpectedly high fungal spore concentrations were measured outdoors during
      winter. The presented pilot database on the inhalable levels of indoor and
      outdoor bio-aerosols can help apportion and better characterize the inhalation
      exposure to these bio-aerosols. Furthermore, the data can be incorporated into
      existing models to quantify the penetration of biological particles into indoor
      environments from outdoors.

PMID- 16420497
TI  - Transport of airborne particles within a room.
AB  - The objective of this study is to test a technique used to analyze contaminant
      transport in the wake of a bluff body under controlled experimental conditions
      for application to aerosol transport in a complex furnished room. Specifically,
      the hypothesis tested by our work is that the dispersion of contaminants in a
      room is related to the turbulence kinetic energy and length scale. This
      turbulence is, in turn, determined by the size and shape of furnishings within
      the room and by the ventilation characteristics. This approach was tested for
      indoor dispersion through computational fluid dynamics simulations and laboratory
      experiments. In each, 3 mum aerosols were released in a furnished room with
      varied contaminant release locations (at the inlet vent or under a desk). The
      realizable k approximately epsilon model was employed in the simulations,
      followed by a Lagrangian particle trajectory simulation used as input for an in
      house FORTRAN code to compute aerosol concentration. For the experiments,
      concentrations were measured simultaneously at seven locations by laser
      photometry, and air velocity was measured using laser Doppler velocimetry. The
      results suggest that turbulent diffusion is a significant factor in contaminant
      residence time in a furnished room. This procedure was then expanded to develop a
      simplified correlation between contaminant residence time and the number of
      enclosing surfaces around a point containing the contaminant. Practical
      Implications The work presented here provides a methodology for relating local
      aerosol residence time to properties of room ventilation and furniture
      arrangement. This technique may be used to assess probable locations of high
      concentration by knowing only the particle release location, furniture
      configuration, inlet and outlet locations, and air speeds, which are all
      observable features. Applications of this method include development of 'rules of
      thumb' for first responders entering a room where an agent has been released and
      selection of sampler locations to monitor conditions in sensitive areas.

PMID- 16420498
TI  - Initial studies of oxidation processes on filter surfaces and their impact on
      perceived air quality.
AB  - Used filters can be a strong sensory pollutant source. Oxidation processes,
      especially those initiated by ozone, may contribute to the pollutants emitted
      from such filters. In the present study, ozone was added to the airstream passing
      through used ventilation filters. Two flow rates were examined. While the
      upstream ozone concentration was approximately 75 ppb, the concentrations
      downstream of the filter were initially 35-50% lower. However, within an hour
      downstream concentrations were only 5-10% lower than those upstream. These filter
      samples were then placed for 48 h in nitrogen, ambient air containing less than 5
      ppb ozone, or ambient air at an elevated temperature. This resulted in partial
      regeneration of the ozone removal capability of the filter. In analogous
      experiments, lower ozone removal occurred when the filter samples were first
      ventilated for 24 h with ozone-free air before making the measurements. Samples
      from a new filter removed <10% of the ozone in the airstream, and removal
      remained relatively constant over time. In companion studies, human subjects
      assessed the air passing through various used filter samples. In the initial
      evaluation each of the four filter samples, taken from the same filter and
      ventilated for 24 h, were assessed to be equivalent. The next evaluation was
      immediately after the samples had been kept for 24 h in either nitrogen, air, air
      at an elevated temperature or ozone. The nitrogen-treated filter was assessed to
      be best, while the ozone-treated filter was assessed to be the worst. The final
      evaluation occurred after ambient air had passed through the 'treated' filters
      for 2 h. All such ventilated filters were assessed to be more acceptable than
      immediately after the 24-h treatments; the ozonized and air-treated filters were
      the most polluting of the four. Practical Implications The present paper supports
      previous findings that loaded ventilation filters can be significant sources of
      sensory pollution. Replacing a loaded filter with a new filter temporarily
      removes this source of pollution. However, the present study does not provide an
      answer to how frequently changes are needed under different conditions. The
      results indicate that in cases of intermittent operation of ventilation systems,
      the airflow through the polluted filters should be restarted in sufficient time
      prior to occupancy to purge odorous pollutants that have accumulated on the
      filter surface. Removal of ozone upstream of the particle filters may further
      improve perceived air quality in the space downstream of the filter bank. Future
      efforts related to the development and application of low-polluting filtration
      systems are warranted.

PMID- 16420499
TI  - Gas cooking, kitchen ventilation, and exposure to combustion products.
AB  - We evaluated a questionnaire-based system for classifying homes into groups with
      distinctly different chances of accumulating combustion products from cooking
      appliances. The system was based on questions about type of cooking appliance,
      type and use of ventilation provisions, and kitchen size. Real-time measurements
      were made of CO, CO(2), temperature, and water vapor, and passive sampling was
      performed of nitrogen oxides, over a week-long period in 74 kitchens. During the
      measurements, inhabitants kept a diary to record appliance use time and use of
      ventilation provisions. The questionnaire-based and diary-based home
      classifications for the 'Chance of Accumulation of Combustion Products' (CACP)
      turned out to agree fairly well. For CO(2) as well as for CO a significant
      difference between the 'high' and 'low' CACP groups was found for the mean
      accumulation in the kitchen during cooking of the combustion generated
      concentrations. These facts are considered to be important experimental evidence
      of the CACP stratification being valid for our study population. In the homes
      studied, NO(2) as well as CO concentrations were found to be lower compared with
      previous studies in The Netherlands. Practical Implications Previous studies on
      indoor combustion product dispersal conducted in the early- to mid-1980s in the
      Netherlands showed much higher NO(2) and CO concentrations than the present
      study. Apparently, the removal of combustion products formed during cooking is
      more efficient in the (mostly newer) homes that we studied than in the homes
      studied in the early- to mid-1980s. More detailed knowledge of kitchen situations
      is needed to improve the CACP model. Future studies can achieve this by using
      questionnaires on the kitchen situation, diaries and real-time measurements of
      the combustion products under consideration.

PMID- 16420500
TI  - Indoor environmental quality in a 'low allergen' school and three standard
      primary schools in Western Australia.
AB  - To investigate indoor environmental quality in classrooms, assessments were
      undertaken in a 'low allergen' school and three standard primary schools in
      Western Australia. Dust allergens, air pollutants and physical parameters were
      monitored in the four schools at four times (summer school term, autumn holiday,
      winter school term and winter holiday) in 2002. The levels of particulate matter
      (PM(10)) and volatile organic compounds were similar between the four primary
      schools. Although slightly decreased levels of dust-mite and cat allergens were
      observed in the 'low allergen' school, the reductions were not statistically
      significant and the allergen levels in all schools were much lower than the
      recommended sensitizing thresholds. However, significantly lower levels of
      relative humidity and formaldehyde level during summer-term were recorded in the
      'low allergen' school. In conclusion, the evidence here suggests that the 'low
      allergen' school did not significantly improve the indoor environmental quality
      in classrooms. Practical Implications School is an important environment for
      children in terms of exposure to pollutants and allergens. By assessing the
      levels of key pollutants and allergens in a low allergen school and three
      standard primary schools in Western Australia, this study provides useful
      information for implementation of healthy building design that can improve the
      indoor environment in schools.

PMID- 16420501
TI  - Letter to the editor.

PMID- 16420502
TI  - Letter to the editor.

PMID- 16420504
TI  - Membranous obstruction of the inferior vena cava and its causal relation to
      hepatocellular carcinoma.
AB  - Although rare in most countries, membranous obstruction of the inferior vena cava
      (MOIVC) occurs more frequently in Nepal, South Africa, Japan, India, China, and
      Korea. The occlusive lesion always occurs at approximately the level of the
      diaphragm. It commonly takes the form of a membrane, but may be a fibrotic
      occlusion of variable length. Controversy exists as to whether MOIVC is a
      developmental abnormality or a result of organization of a thrombus in the
      hepatic portion of the inferior vena cava. The outstanding physical sign
      associated with MOIVC are large truncal collateral vessels with a cephalad flow.
      A dilated vena azygous is seen on chest radiography. Definitive diagnosis is made
      by contrast inferior vena cavography. The long-standing obstruction to hepatic
      venous flow causes severe centrolobular fibrosis and predisposes to the
      development of hepatocellular carcinoma (HCC). Percutaneous balloon angioplasty,
      transatrial membranotomy, or more complex vena caval and portal decompression
      surgery should be performed to prevent these complications. HCC occurs in more
      than 40% of South African Black and Japanese patients with MOIVC, but less often
      in other populations. It is thought to result from the tumour-promoting effect of
      continuous hepatocyte necrosis, although the associated environmental risk
      factors have not been identified.

PMID- 16420505
TI  - Therapeutic strategies against TGF-beta signaling pathway in hepatic fibrosis.
AB  - Hepatic fibrosis is the common wound-healing response to chronic liver injury. In
      this process, activation of hepatic stellate cells is characteristic of cell
      proliferation and migration, production of collagen and other extracellular
      matrix (ECM) molecules, and contraction after transforming into myofibroblasts.
      It has been shown that the fibrogenic process is prominently regulated by
      transforming growth factor-beta1 (TGF-beta1) and that the specific blockade of
      TGF-beta1/Smad3 signaling may therapeutically intervene the fibrosis of various
      tissues. In this review, we attempt to integrate recent advances in the
      understanding of the mechanisms underlying TGF-beta1/Smad3 pathway modulation of
      ECM gene expression in the context of liver fibrosis, discuss intervention
      strategies targeting the blockade of related signal pathways, and look into novel
      ways to the safe and efficacious prevention and treatment of hepatic fibrosis.

PMID- 16420506
TI  - Premature telomere shortening and impaired regenerative response in hepatocytes
      of individuals with NAFLD.
AB  - AIMS: The risk factors associated with poor prognosis of nonalcoholic fatty liver
      disease (NAFLD) are not fully understood. Our aim was to assess the role of
      progressive hepatocellular telomere shortening in the clinical course of NAFLD.
      METHODS: We measured average telomere lengths in liver tissue samples from 44
      patients with NAFLD by quantitative fluorescence in situ hybridization using a
      telomere-specific probe. Patients in which telomeres measured at least 80% of the
      lengths of age-matched controls were categorized as group A. Those patients with
      telomeres measuring less than 80% of the control lengths formed group B. RESULTS:
      Within group B, some samples showed a remarkable shortening of hepatocyte
      telomeres in younger patients, whereas some group A patients showed almost normal
      telomere lengths until their seventies. Among clinicopathological factors, body
      mass index (BMI), homeostasis model assessment insulin resistance (HOMA-IR),
      histological degree of steatosis and intensity of 8-hydroxy-2'-deoxyguanosine (8
      OHdG) immunostaining were all significantly higher in group B than in group A. Ki
      67 immunohistochemistry demonstrated that group B liver tissues were
      significantly less proliferative than those from group A, despite no significant
      difference in the necroinflammatory activities of group A and B samples. In group
      B patients, the ratios of Ki-67 positive index to alanine aminotransferase value
      were significantly lower than group A. CONCLUSIONS: Greater insulin resistance
      can result in more severe hepatic steatosis among group B patients, leading to an
      overproduction of reactive oxygen species, which may accelerate telomere erosion.
      Furthermore the regenerative response of hepatocytes with prominent telomere
      shortening may be impaired, making these cells vulnerable to the effect of a
      'second-hit' insult.

PMID- 16420507
TI  - Serum cytokine and soluble cytokine receptor levels in patients with non
      alcoholic steatohepatitis.
AB  - BACKGROUND: Although the pathogenesis of non-alcoholic steatohepatitis (NASH)
      remains poorly understood, proinflammatory cytokines seem to play an important
      role in the process of NASH. We have undertaken this study in order to elucidate
      the role of proinflammatory cytokines and their soluble receptors in NASH
      patients. METHODS: Serum cytokines and soluble cytokine receptors levels were
      determined using an enzyme-linked immunosorbent assay kit in 23 patients with
      NASH, 21 patients with simple steatosis, and 18 healthy volunteers. RESULTS:
      Patients with NASH had significantly higher serum tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-6 (IL-6) levels than did the simple steatosis
      patients. Similarly, when compared with simple steatosis, NASH was associated
      with higher soluble TNF receptor 1 (sTNFR1) and soluble IL-6 receptor (sIL-6R)
      levels, and a significant positive correlation was seen between the levels of
      sTNFR1 and aminotranferases in NASH patients. CONCLUSIONS: This study shows that
      circulating TNF-alpha/sTNFR1 and IL-6/sIL-6R levels are significantly increased
      in NASH patients as compared with simple steatosis patients and healthy
      volunteers, and that these increased levels may be implicated in the pathogenesis
      of NASH.

PMID- 16420508
TI  - Laparoscopic findings in patients with nonalcoholic steatohepatitis.
AB  - BACKGROUND/AIMS: Laparoscopic observation of the liver is important to diagnose
      liver conditions accurately. However, the laparoscopic findings of nonalcoholic
      steatohepatitis (NASH) have not been characterized. The aim of this study was to
      clarify the laparoscopic characteristics of NASH. METHODS: Twenty-four patients
      were enrolled. The degrees of hepatomegaly, color and irregularity of the liver
      surface, and the presence of depressions, patches, and vesicles were
      investigated. These laparoscopic findings were compared among NASH, alcoholic
      liver disease (ALD), and autoimmune hepatitis (AIH). RESULTS: Mild hepatomegaly,
      dullness of the liver edge, increased fat accumulation of the round ligament, and
      whitish markings were found in most of the patients with NASH. Small depressions
      were observed in approximately 70% of the patients. As fibrosis developed, the
      liver surface became whiter and more uneven. Compared with patients with ALD and
      AIH, increased fat accumulation of the round ligament and dullness of the liver
      edge were observed more frequently in those with NASH. However, coarse and groove
      like depressions were rare in NASH patients. CONCLUSIONS: Several findings,
      including mild hepatomegaly, increased fat accumulation of the round ligament,
      rounded liver edge, whitish markings, and small depressions were common in
      patients with NASH. However, coarse and groove-like depressions were rare. These
      findings may be helpful for confirming a diagnosis of NASH.

PMID- 16420509
TI  - Comparison of outcome in patients with cirrhosis and ascites following treatment
      with albumin or a synthetic colloid: a randomised controlled pilot trail.
AB  - BACKGROUND: The question of which colloid (albumin or synthetic colloids) used
      for plasma expansion following paracentesis or other complications requiring
      fluid loading in patients with cirrhosis remains controversial. AIMS: To compare
      outcome and hospital-related cost in patients with cirrhosis treated with 20%
      human albumin with those treated with a synthetic colloid (3.5% polygeline).
      METHODS: The primary end point was occurrence of a first liver-related
      complication. RESULTS: When the trial was prematurely discontinued because of
      safety concerns about bovine-derived products, 30 patients were assigned to
      receive albumin and 38 were assigned to receive a synthetic colloid. Sixty-three
      patients were included for ascites removal by paracentesis and five patients for
      ascites removal by paracentesis and renal impairment. The median time to first
      liver-related complication was not significantly longer in the albumin group (20
      vs. 7 days). However, the total number of liver-related complications adjusted to
      a 100-day period was significantly lower in the albumin group. The median
      hospital cost for a 30-day period was significantly lower in the albumin group
      (1915 euros vs. 4612 euros). CONCLUSIONS: In patients with cirrhosis and ascites,
      human albumin appears to be more effective in preventing liver-related
      complications than synthetic colloid. This may be associated with decreased
      hospital costs.

PMID- 16420510
TI  - Occurrence of cirrhosis-related complications is a time-dependent prognostic
      predictor independent of baseline model for end-stage liver disease score.
AB  - BACKGROUND: The model for end-stage liver disease (MELD) is used to prioritize
      cirrhotic patients awaiting liver transplantation. Many cirrhosis-related
      complications are indications for transplantation but are not included in MELD.
      This study investigated the impact of these complications on survival and
      association with MELD. METHODS: The mortality risk of cirrhosis-related
      complications, including bleeding esophageal varices, spontaneous bacterial
      peritonitis, hepatic encephalopathy, hepatorenal syndrome and hepatic
      decompensation, was analyzed using a time-dependent Cox regression model in 227
      cirrhotic patients. RESULTS: A total of 281 episodes of complications occurred in
      142 (63%) patients. Patients who died had a significantly higher baseline MELD
      score compared with those who survived (14.5 +/- 4.5 vs 12.8 +/- 3.9, P = 0.004).
      There was no significant difference in the MELD score between patients with and
      without the occurrence of complications (13.6 +/- 4.3 vs 12.9 +/- 4.0, P =
      0.093). Patients with a higher baseline MELD score tended to develop early
      complications (rho = -0.598, P< 0.001). Using the Cox regression model, the risk
      ratio of mortality was 4.9 (95% confidence interval: 3.9-6.3, P< 0.0001) for each
      additional episode of complication. CONCLUSIONS: The mortality risk increases as
      the number of complication episodes increases. While patients with repeated
      complications have a poor outcome, they do not necessarily have a higher baseline
      MELD score and could be down-staged in the MELD era.

PMID- 16420511
TI  - Probability of liver cancer and survival in HCV-related or alcoholic
      decompensated cirrhosis. A study of 377 patients.
AB  - BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress
      to cirrhosis and hepatocellular carcinoma (HCC), few data are available about
      survival and probability of developing HCC in decompensated cirrhosis of both
      aetiologies. METHODS: This study identified factors related with probability of
      developing HCC and survival in a cohort of 377 consecutive patients with
      decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177
      cases) without known HCC, hospitalized for their first hepatic decompensation, as
      well as to evaluate differences between both aetiologies. Patients were followed
      for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients
      (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p
      = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol,
      respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC
      development, while baseline age and Child-Turcotte-Pugh score were independently
      correlated with survival. CONCLUSION: Survival in decompensated HCV-related or
      alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score,
      without differences in cirrhosis aetiology. The risk of developing HCC is greater
      in HCV-related cirrhosis than in alcoholic cirrhosis.

PMID- 16420512
TI  - A randomized trial of 24- vs. 48-week courses of PEG interferon alpha-2b plus
      ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in
      Taiwan.
AB  - BACKGROUND: To assess the efficacy of 24- or 48-week peginterferon/ribavirin
      treatment of Taiwanese patients with chronic hepatitis C virus genotype-1b (HCV
      1b) infection, and to identify subgroups of patients in whom the 48-week
      treatment has benefits. METHODS: We assigned 60 patients receiving peginterferon
      alpha-2b (80-100 mcg/week) plus ribavirin (1000-1200 mg/day), depending on body
      weight, for 24 or 48 weeks, with a 3:1 randomization ratio. RESULTS: The
      sustained virological response (SVR) rate was significantly higher in the 48-week
      (80.0%, 12/15) than in the 24-week group (48.9%, 22/45, P < 0.05). The 60
      patients were classified into two subgroups according to the presence of
      unfavorable baseline predictors: viral loads > or = 400,000 IU/ml or a hepatic
      fibrosis score of 3-4. In 19 patients without an unfavorable predictor, the SVR
      rate was comparable in the 24-week (78.6%) and 48-week (75.0%) groups; in
      patients with either unfavorable predictors, the SVR rate was significantly
      higher in the 48-week (81.1%, 9/11) than in the 24-week group (36.7%, 11/30, P =
      0.015). The discontinuation rate was significantly higher in the 48-week (20.0%,
      3/15) than in the 24-week group (2.2%, 1/45, P < 0.05). CONCLUSION: A 48-week
      course of peginterferon-alpha-2b/ribavirin was more effective than a 24-week
      course in Taiwanese HCV-1b patients, mainly in those with high viral loads and/or
      advanced hepatic fibrosis.

PMID- 16420513
TI  - Prognostic analysis in chronic hepatitis B patients: a retrospective study of 216
      cases about Scheuer scores, in situ expression of viral antigens and tissue
      hepatitis B virus DNA levels.
AB  - BACKGROUND: Most of the previous studies of patients with chronic hepatitis B
      virus (HBV) infection concentrated on serum samples. Liver biopsy specimens for
      HBV have not been systematically analyzed. This study was performed to analyze
      some histopathological indicators (Scheuer scores, the expression of HBV antigens
      in situ, HBV DNA quantification) in the biopsy samples and showed the
      relationship among them and the prognosis of chronic hepatitis. METHODS: A total
      of 216 consecutive chronic HBV-infected patients were followed up by clinical and
      laboratory data and classified into two groups at first: carcinogenesis and non
      carcinogenesis. The non-carcinogenesis also included two groups: cirrhosis and
      non-cirrhosis. The non-cirrhosis was still divided into fluctuation and
      normalization at last. Histological activity index was described by Scheuer
      scores. Two-step immunohistochemical staining showed the expression of viral
      antigens in situ. Tissue HBV DNA levels were determined by fluorescence
      quantitative real-time PCR. RESULTS: Regression analysis revealed significant
      positive correlations between the expression of hepatitis B e antigen (HBeAg) and
      grading, as well as between hepatitis Bx (HBx) protein and grading or staging of
      Scheuer scores. Positive correlations between grading or staging and prognosis
      were statistically significant. The expressions of HBeAg and HBx protein were
      higher in patients with cirrhosis than those without cirrhosis. Scheuer score was
      the most important indicator of prognosis. CONCLUSIONS: HBeAg and HBx protein can
      be used as indicators of hepatitis activity and their positive expressions
      increase the risk for cirrhosis remarkably. In addition to be a marker of liver
      damage, Scheuer score is the most reliable indicator of the prognosis.

PMID- 16420514
TI  - Measurement of hepatitis B virus core-related antigen is valuable for identifying
      patients who are at low risk of lamivudine resistance.
AB  - OBJECTIVE: The clinical usefulness of hepatitis B virus core-related antigen
      (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the
      occurrence of lamivudine resistance in patients with chronic hepatitis B.
      PATIENTS: Of a total of 81 patients who were treated with lamivudine, 25 (31%)
      developed lamivudine resistance during a median follow-up period of 19.3 months.
      RESULTS: The pretreatment positive rate of HBe antigen, or pretreatment levels of
      HBVcrAg or HBV DNA did not differ between patients with and without lamivudine
      resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of
      lamivudine administration; however, the level of HBVcrAg decreased significantly
      more slowly than that of HBV DNA. The occurrence of lamivudine resistance was
      significantly less frequent in the 56 patients whose HBV DNA level was less than
      2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The
      cumulative rate of lamivudine resistance was as high as 70% within 2 years in the
      latter group, while it was only 28% in the former group. Lamivudine resistance
      did not occur during the follow-up period in the 19 patients whose HBVcrAg level
      was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of
      the remaining patients within 2 years. CONCLUSION: These results suggest that
      measurement of HBV DNA is valuable for identifying patients who are at high risk
      of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg
      is valuable for identifying those who are at low risk of lamivudine resistance.

PMID- 16420515
TI  - Effect of platelet-activating factor (PAF) receptor antagonist (BN52021) on
      acetaminophen-induced acute liver injury and regeneration in rats.
AB  - BACKGROUND: Platelet-activating factor (PAF) is an endogenous lipid mediator that
      plays a key role in catalyzing various pro-inflammatory processes associated with
      acute liver injury. In the present study, the possible influence of PAF-R
      antagonist (BN52021) on the protection of liver injury after 4
      hydroxyacetanilide, N-acetyl-p-aminophenol, paracetamol (APAP) intoxication was
      investigated. METHODS: Thereby, one group of rats was treated with a toxic dose
      of APAP (3.5 g/kg body weight (b.w.). The animals were killed at 56, 66, 72, 84
      and 96 h after treatment. RESULTS: APAP was found to cause an acute hepatic
      injury, evident by alterations of biochemical (serum enzymes: aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase)
      and liver histopathological (degree of necrosis and apoptosis) indices, which was
      followed by liver regeneration, evident by three independent indices ([3H]
      thymidine incorporation into hepatic DNA, liver thymidine kinase activity and
      hepatocyte mitotic index). The protective effects of BN52021 were qualified
      during post-treatment time by: (1) significant reduction of hepatic injury as
      showed by all biochemical and histological parameters, (2) high decrease of
      regenerating activity showed by three regenerative markers and (3) remarkable
      increase of PAF-acetylhydrolase (PAF-AH) activity. CONCLUSION: These results
      suggest that PAF may play an important role in APAP-induced liver injury and
      regeneration, and PAF-R antagonist (BN52021) attenuates liver damage.

PMID- 16420516
TI  - High expression of eosinophil chemoattractant ecalectin/galectin-9 in drug
      induced liver injury.
AB  - BACKGROUND: Ecalectin/galectin-9 (ECL/GL9) is an eosinophil chemoattractant
      isolated from T lymphocytes. Drug-induced liver injury (DILI), often caused by an
      allergic mechanism, is occasionally accompanied by eosinophilic infiltration. In
      this study, we intended to determine whether DILI can induce augmentation of
      ECL/GL9 expression. Further, we investigated whether this augmentation is
      associated with tissue eosinophilia. METHODS: We examined the expression of
      ECL/GL9 in biopsy specimens of DILI using the immunohistochemical technique. A
      rabbit anti-ECL/GL9 antibody was produced by immunizing rabbits with synthetic
      peptide corresponding to a molecular epitope of ECL/GL9. Thereafter,
      immunohistochemical staining with the use of this antibody was performed on 16
      DILI needle biopsy specimens, and on biopsy specimens of chronic viral hepatitis,
      liver cirrhosis, and normal liver tissues as controls. RESULTS: In all cases of
      DILI specimens, but not in control liver specimens, a clear positive staining for
      ECL/GL9 was observed. Such positive staining was noted on Kupffer cells,
      fibroblasts, and histiocytes, but not on lymphocytes or hepatocytes. However, the
      intensity of immunolabeling did not correlate with the extent of eosinophile
      leukocyte infiltration. CONCLUSION: High expression of ECL/GL9 is suggested to be
      a specific finding of DILI. However, tissue eosinophilia in DILI cannot be
      explained by the augmentation of ECL/GL9 expression.

PMID- 16420517
TI  - Design-based stereological estimation of hepatocyte number, by combining the
      smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic
      antigen polyclonal antibodies.
AB  - BACKGROUND/AIMS: Hepatocytes (HEP) have been the major target for structural
      quantification in the liver, but an estimation of their total number (N), their
      percentage in relation to the global number of liver cells and the evaluation of
      the percentage of binucleated hepatocytes (BnHEPs) have never been performed with
      modern design-based stereological techniques. The establishment of sound
      technical guidelines and baseline quantitative data in non-pathological
      conditions are relevant to properly evaluate HEP hyperplasia and BnHEP responses.
      METHODS: In this study, we combined immunocytochemistry with sound design-based
      stereology for estimating the N of HEP and the N of non-hepatocytic cells (NHCs).
      For obtaining systematic uniform random sections (30 microm thick), a smooth
      fractionator sampling scheme was applied to the liver of five male Wistar rats (3
      month old). Those sections were immunostained with polyclonal antibodies against
      carcinoembryonic antigen. Because biliary canaliculi were then marked, an
      unequivocal counting of mononucleated hepatocytes (MnHEP) and BnHEP was allowed.
      RESULTS: The N of HEP was estimated to be 1.93 x 10(9), with a coefficient of
      error (CE) of 0.02, corresponding to 129 x 10(6) HEP/g of liver. BnHEP
      represented 26% of total HEP number. The N of NHC was estimated as 1.31 x 10(9)
      (CE=0.02). CONCLUSION: The strategy here presented provides a reliable method for
      accessing the N of HEP (distinguishing MnHEP from BnHEP) in situations in which
      these parameters are relevant, namely for evaluating the magnitude of an
      hyperplastic liver response from its very early onset.

PMID- 16420518
TI  - Effect of celecoxib on experimental liver fibrosis in rat.
AB  - BACKGROUND/AIM: Cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes
      prostaglandin synthesis, has been implicated in a number of hepatic stellate cell
      (HSC) functions. In the current study, we assessed the in vivo effect of
      celecoxib, a COX-2-selective inhibitor, in experimental liver fibrosis in rats.
      METHODS: Male Sprague-Dawley rats received experimental treatments for 5 weeks.
      Serum alanine transminase at the time of sacrifice was measured. Quantitative
      assessment of liver fibrosis was performed by computerized morphometry.
      Expression of COX-2, alpha smooth muscle actin and connective tissue growth
      factor (CTGF) was evaluated by immunohistochemistry. Real-time quantitative PCR
      was used to determine the expression of genes associated with fibrogenesis and
      extracellular matrix degradation. RESULTS: Liver fibrosis was significantly worse
      in rats that received both carbon tetrachloride (CCl4) and celecoxib, compared
      with rats that received CCl4 and gavage of water (P = 0.037). There was also more
      HSC activation, and upregulation of collagen alpha1(I), heat-shock protein 47,
      alphaB crystallin, matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor
      of MMP (TIMP)-2. The expression of TIMP-1 and CTGF was not significantly
      different between the two groups. The pro-fibrogenic effect of celecoxib in toxin
      induced liver fibrosis in rats was further confirmed in thioacetamide model of
      liver injury. CONCLUSIONS: Celecoxib potentiates experimental liver fibrosis;
      further studies are warranted to investigate the potential pro-fibrogenic effect
      of celecoxib in other animal models of liver fibrosis and in patients with
      chronic hepatitis.

PMID- 16420519
TI  - Differential caspase-9-dependent signaling pathway between tumor necrosis factor
      receptor- and Fas-mediated hepatocyte apoptosis in mice.
AB  - BACKGROUND/AIMS: Two apoptosis signaling pathways, which are used by different
      cell types, are identified. The activation of caspases is critical for the
      apoptosis process. The aim of this study was to investigate the effects of the
      caspase-9 inhibitor Ac-LEHD-CHO on tumor necrosis factor receptor (TNFR)- and Fas
      mediated hepatocyte apoptosis in vivo, in order to evaluate the similarities and
      distinctions between TNFR- and Fas-mediated signaling pathways. METHODS: BALB/c
      mice were intravenously injected with d-galactosamine (GalN, 20 mg/mouse)/tumor
      necrosis factor-alpha (TNF-alpha, 0.5 microg/mouse), or alphaFas (10
      microg/mouse) 30 min after treatment with the caspase-9 inhibitor Ac-LEHD-CHO or
      pan-caspase inhibitor Z-VAD-fmk. Liver injury was assessed biochemically and
      histologically. Cytochrome c release and processing of procaspases in the liver
      were analyzed by Western blotting. Activities of caspases were measured using a
      fluorogenic peptide substrate. RESULTS: Pretreatment with Z-VAD-fmk prevented
      liver injury and hepatocyte apoptosis induced by either GalN/TNF-alpha or
      alphaFas. On the other hand, pretreatment with Ac-LEHD-CHO prevented GalN/TNF
      alpha-induced hepatotoxicity and hepatocyte apoptosis but not alphaFas-induced
      liver injury and apoptosis. Both inhibitors reduced the activities of caspase-9
      and -3 in the livers of mice administered by GalN/TNF-alpha. However, unlike Z
      VAD-fmk, Ac-LEHD-CHO did not inhibit caspase-3 activation in alphaFas-treated
      mice, although this inhibitor attenuated caspase-9. CONCLUSION: Fas may rely on
      both caspase-8 activation (extrinsic pathway) and mitochondria (intrinsic
      pathway) to activate caspase-3. If the mitochondria-dependent pathway is blocked,
      the other pathway can compensate. In contrast, TNFR may mediate hepatocellular
      apoptosis mainly through the mitochondria-mediated caspase-9 activation pathway
      alone.

PMID- 16420520
TI  - Compound exocytosis: mechanisms and functional significance.
AB  - Compound exocytosis occurs in many cell types. It represents a specialized form
      of secretion in which vesicles undergo fusion with each other as well as with the
      plasma membrane. In most cases, compound exocytosis occurs sequentially, with
      deeper-lying vesicles fusing, after a delay, with vesicles that have already
      fused with the plasma membrane. However, in some cells, vesicles can also
      apparently fuse with each other intracellularly before any interaction with the
      plasma membrane. In this review, we discuss the general features of compound
      exocytosis, and the features that are specific to particular cells. We consider
      mechanisms that might impose the requirement for vesicles to fuse with the plasma
      membrane before they become able to fuse with each other, the possibility that
      there are biochemical differences between vesicle-plasma membrane fusion events
      and subsequent secondary homotypic vesicle fusion events, and the role that
      cytoskeletal elements might play in the stabilization of fused vesicles, in order
      to permit secondary fusion events. Finally, we discuss the likely physiological
      significance of compound exocytosis in the various cell types in which it exists.

PMID- 16420521
TI  - Dominant and recessive distal renal tubular acidosis mutations of kidney anion
      exchanger 1 induce distinct trafficking defects in MDCK cells.
AB  - Distal renal tubular acidosis (dRTA), a kidney disease resulting in defective
      urinary acidification, can be caused by dominant or recessive mutations in the
      kidney Cl-/HCO3- anion exchanger (kAE1), a glycoprotein expressed in the
      basolateral membrane of alpha-intercalated cells. We compared the effect of two
      dominant (R589H and S613F) and two recessive (S773P and G701D) dRTA point
      mutations on kAE1 trafficking in Madin-Darby canine kidney (MDCK) epithelial
      cells. In contrast to wild-type (WT) kAE1 that was localized to the basolateral
      membrane, the dominant mutants (kAE1 R589H and S613F) were retained in the
      endoplasmic reticulum (ER) in MDCK cells, with a few cells showing in addition
      some apical localization. The recessive mutant kAE1 S773P, while misfolded and
      largely retained in the ER in non-polarized MDCK cells, was targeted to the
      basolateral membrane after polarization. The other recessive mutants, kAE1 G701D
      and designed G701E, G701R but not G701A or G701L mutants, were localized to the
      Golgi in both non-polarized and polarized cells. The results suggest that
      introduction of a polar mutation into a transmembrane segment resulted in Golgi
      retention of the recessive G701D mutant. When coexpressed, the dominant mutants
      retained kAE1 WT intracellularly, while the recessive mutants did not.
      Coexpression of recessive G701D and S773P mutants in polarized cells showed that
      these proteins could interact, yet no G701D mutant was detected at the
      basolateral membrane. Therefore, compound heterozygous patients expressing both
      recessive mutants (G701D/S773P) likely developed dRTA due to the lack of a
      functional kAE1 at the basolateral surface of alpha-intercalated cells.

PMID- 16420522
TI  - Microtubules facilitate autophagosome formation and fusion of autophagosomes with
      endosomes.
AB  - Nutrient deprivation of eukaryotic cells provokes a variety of stress responses,
      including autophagy. Autophagy is carried out by autophagosomes which sequester
      cytosolic components and organelles for degradation after fusion with protease
      containing endosomes. To determine the role of microtubules in autophagy, we used
      nocodazole and vinblastine to disrupt microtubules and independently measured
      formation and fusion of autophagsosomes in primary rat hepatocytes. By measuring
      the translocation of GFP-LC3, an autophagosomal marker, to autophagosomes and the
      lipidation of GFP-LC3, we quantified the rate and magnitude of autophagosome
      formation. Starvation increased both the rate of autophagosome formation over the
      basal level and the total number of autophagosomes per cell. Maximal
      autophagosome formation required an intact microtubule network. Fusion of
      autophagosomes with endosomes, assayed by acquisition of protease-inhibitor
      sensitivity as well as overlap with LysoTracker Red-positive endosomes, required
      intact microtubules. Live-cell imaging demonstrated that autophagosomes were
      motile structures, and their movement also required microtubules. Interestingly,
      vinblastine stimulated autophagosome formation more than twofold before any
      discernable change in the microtubule network was observed. Stimulation of
      autophagosome formation by vinblastine was independent of nutrients and mTOR
      activity but was inhibited by depletion of the Autophagy proteins Atg5 and Atg6,
      known to be required for autophagy.

PMID- 16420523
TI  - N-glycans mediate apical recycling of the sialomucin endolyn in polarized MDCK
      cells.
AB  - Apical and basolateral proteins are maintained within distinct membrane
      subdomains in polarized epithelial cells by biosynthetic and postendocytic
      sorting processes. Sorting of basolateral proteins in these processes has been
      well studied; however, the sorting signals and mechanisms that direct proteins to
      the apical surface are less well understood. We previously demonstrated that an N
      glycan-dependent sorting signal directs the sialomucin endolyn to the apical
      surface in polarized Madin-Darby canine kidney cells. Terminal processing of a
      subset of endolyn's N-glycans is key for polarized biosynthetic delivery to the
      apical membrane. Endolyn is subsequently internalized, and via a cytoplasmic
      tyrosine-based sorting motif is targeted to lysosomes from where it
      constitutively cycles to the cell surface. Here, we examine the polarized sorting
      of endolyn along the postendocytic pathway in polarized cells. Our results
      suggest that similar N-glycan sorting determinants are required for apical
      delivery of endolyn along both the biosynthetic and the postendocytic pathways.

PMID- 16420524
TI  - Insulin-regulated aminopeptidase marks an antigen-stimulated recycling
      compartment in mast cells.
AB  - Insulin-regulated aminopeptidase (IRAP) is a marker for insulin-sensitive
      recycling compartments of fat and muscle cells that contain the glucose
      transporter isoform GLUT4. Unlike GLUT4, IRAP is expressed in many other cell
      types. Thus, it is a potential marker for regulated recycling compartments that
      are analogous to GLUT4 vesicles. In bone marrow-derived mast cells, IRAP is
      highly expressed and localizes to an intracellular compartment different from
      secretory granules. Using cell-surface biotinylation, we determined that IRAP
      underwent rapid redistribution to the plasma membrane on antigen/immunoglobulin E
      (IgE) stimulation and was re-internalized within 30 min. When granule exocytosis
      was inhibited, by removing extracellular calcium, adding the protein kinase C
      inhibitor bisindolylmaleimide or the phosphatidylinositol 3-kinase inhibitor
      wortmannin, IRAP redistribution was still detected in stimulated cells. However,
      the redistribution of IRAP required intracellular calcium. By immunofluorescence,
      IRAP significantly co-localized with the transferrin receptor (TfR), a marker for
      constitutively recycling endosomes. However, antigen/IgE stimulation did not
      increase TfR on the cell surface, indicating that IRAP and TfR may follow
      different pathways to the plasma membrane. In rat peritoneal mast cells, the
      distributions of IRAP and TfR overlapped to only a limited extent, indicating
      that overlap may decrease with cell differentiation. We propose that IRAP
      vesicles represent a second IgE-sensitive exocytotic compartment in mast cells,
      which is regulated differently from secretory granules, and that these vesicles
      may be similar to GLUT4 vesicles.

PMID- 16420525
TI  - The retention factor p11 confers an endoplasmic reticulum-localization signal to
      the potassium channel TASK-1.
AB  - The interaction of the adaptor protein p11, also denoted S100A10, with the C
      terminus of the two-pore-domain K+ channel TASK-1 was studied using yeast two
      hybrid analysis, glutathione S-transferase pull-down, and co-immunoprecipitation.
      We found that p11 interacts with a 40 amino-acid region in the proximal C
      terminus of the channel. In heterologous expression systems, deletion of the p11
      interacting domain enhanced surface expression of TASK-1. Attachment of the p11
      interacting domain to the cytosolic tail of the reporter protein CD8 caused
      retention/retrieval of the construct in the endoplasmic reticulum (ER).
      Attachment of the last 36 amino acids of p11 to CD8 also caused ER localization,
      which was abolished by removal or mutation of a putative retention motif
      (H/K)xKxxx, at the C-terminal end of p11. Imaging of EGFP-tagged TASK-1 channels
      in COS cells suggested that wild-type TASK-1 was largely retained in the ER.
      Knockdown of p11 with siRNA enhanced trafficking of TASK-1 to the surface
      membrane. Our results suggest that binding of p11 to TASK-1 retards the surface
      expression of the channel, most likely by virtue of a di-lysine retention signal
      at the C-terminus of p11. Thus, the cytosolic protein p11 may represent a
      'retention factor' that causes localization of the channel to the ER.

PMID- 16420526
TI  - Structural analysis of the interaction between the SNARE Tlg1 and Vps51.
AB  - Membrane fusion in cells involves the interaction of SNARE proteins on apposing
      membranes. Formation of SNARE complexes is preceded by tethering events, and a
      number of protein complexes that are thought to mediate this have been
      identified. The VFT or GARP complex is required for endosome-Golgi traffic in
      yeast. It consists of four subunits, one of which, Vps51, has been shown to bind
      specifically to the SNARE Tlg1, which participates in the same fusion event. We
      have determined the structure of the N-terminal domain of Tlg1 bound to a peptide
      from the N terminus of Vps51. Binding depends mainly on residues 18-30 of Vps51.
      These form a short helix which lies in a conserved groove in the three-helix
      bundle formed by Tlg1. Surprisingly, although both Vps51 and Tlg1 are required
      for transport to the late Golgi from endosomes, removal of the Tlg1-binding
      sequences from Vps51 does not block such traffic in vivo. Thus, this particular
      interaction cannot be crucial to the process of vesicle docking or fusion.

PMID- 16420527
TI  - COG complex-mediated recycling of Golgi glycosyltransferases is essential for
      normal protein glycosylation.
AB  - Defects in conserved oligomeric Golgi (COG) complex result in multiple
      deficiencies in protein glycosylation. On the other hand, acute knock-down (KD)
      of Cog3p (COG3 KD) causes accumulation of intra-Golgi COG complex-dependent (CCD)
      vesicles. Here, we analyzed cellular phenotypes at different stages of COG3 KD to
      uncover the molecular link between COG function and glycosylation disorders. For
      the first time, we demonstrated that medial-Golgi enzymes are transiently
      relocated into CCD vesicles in COG3 KD cells. As a result, Golgi modifications of
      both plasma membrane (CD44) and lysosomal (Lamp2) glycoproteins are distorted.
      Localization of these proteins is not altered, indicating that the COG complex is
      not required for anterograde trafficking and accurate sorting. COG7 KD and double
      COG3/COG7 KD caused similar defects with respect to both Golgi traffic and
      glycosylation, suggesting that the entire COG complex orchestrates recycling of
      medial-Golgi-resident proteins. COG complex-dependent docking of isolated CCD
      vesicles was reconstituted in vitro, supporting their role as functional
      trafficking intermediates. Altogether, the data suggest that constantly cycling
      medial-Golgi enzymes are transported from distal compartments in CCD vesicles.
      Dysfunction of COG complex leads to separation of glycosyltransferases from
      anterograde cargo molecules passing along secretory pathway, thus affecting
      normal protein glycosylation.

PMID- 16420528
TI  - Dynamics of membrane clathrin-coated structures during cytokinesis.
AB  - Remodeling of cell membranes takes place during motile processes such as cell
      migration and cell division. Defects of proteins involved in membrane dynamics,
      including clathrin and dynamin, disrupt cytokinesis. To understand the function
      of clathrin-containing structures (CCS) in cytokinesis, we have expressed a green
      fluorescent protein (GFP) fusion protein of clathrin light chain a (GFP-clathrin)
      in NRK epithelial cells and recorded images of dividing cells near the ventral
      surface with a spinning disk confocal microscope. Punctate GFP-CCS underwent
      dynamic appearance and disappearance throughout the ventral surface. Following
      anaphase onset, GFP-CCS between separated chromosomes migrated toward the equator
      and subsequently disappeared in the equatorial region. Movements outside
      separating chromosomes were mostly random, similar to what was observed in
      interphase cells. Directional movements toward the furrow were dependent on both
      actin filaments and microtubules, while the appearance/disappearance of CCS was
      dependent on actin filaments but not on microtubules. These results suggest that
      CCS are involved in remodeling the plasma membrane along the equator during
      cytokinesis. Clathrin-containing structures may also play a role in transporting
      signaling or structural components into the cleavage furrow.

PMID- 16420529
TI  - Syntaxin 9 is enriched in skin hair follicle epithelium and interacts with the
      epidermal growth factor receptor.
AB  - We describe a novel syntaxin family member, syntaxin 9 (Syn 9), which does not
      possess a typical C-terminal hydrophobic tail anchor. Syn 9 has, however, a Q
      SNARE domain and an overall homology to syntaxins (with the highest overall
      homology with mammalian syntaxin 11). Syn 9 is enriched in some epithelial cells,
      particularly that of the stomach lining and the skin. At the skin, it is found in
      the epidermal layers as well as structures associated with hair follicles. A
      biochemical interaction screen revealed that Syn 9 interacts specifically with
      the epidermal growth factor (EGF) receptor. Overexpression of Syn 9 perturbed EGF
      receptor endocytosis but does not appear to affect the internalization of the
      transferrin receptor. Syn 9 may therefore have a role in EGF receptor transport
      and signaling in certain epithelial cell types.

PMID- 16420530
TI  - The inner tegument promotes herpes simplex virus capsid motility along
      microtubules in vitro.
AB  - After viral fusion, capsids of the neurotropic herpes simplex virus are
      transported along microtubules (MT) to the nuclear pores for viral genome
      uncoating, nuclear transcription and replication. After assembly and egress from
      the nucleus, cytosolic capsids are transported to host membranes for secondary
      envelopment or to the axon terminal for further viral spread. Using GFP-tagged
      capsids, Cy3-labelled MT and cytosol, we have reconstituted viral capsid
      transport in vitro. In the presence of ATP, capsids moved along MT up to 30
      microm. Blocking the function of dynactin, a cofactor of dynein and kinesin-2,
      inhibited the transport. Removing outer tegument proteins from the capsids
      increased in vitro motility. In contrast, capsids isolated from infected nuclei
      that were devoid of inner as well as outer tegument proteins showed little
      interaction with dynein and its cofactor dynactin. Our data suggest that the
      inner tegument of alphaherpesviruses contains viral receptors for MT motors.

PMID- 16420531
TI  - Increased laser Doppler flow in skin tumors corresponds to elevated vessel
      density and reactive hyperemia.
AB  - BACKGROUND/PURPOSE: Tumor angiogenesis plays a key role in tumor growth and
      formation of metastasis. Quantitative analysis of tumor blood flow is a
      prerequisite for developing novel treatment strategies such as antiangiogenic and
      antivascular treatment options. Laser Doppler flow in malignant melanomas has
      been shown to be increased compared with normal skin and melanocytic nevi. This
      study investigated whether this phenomenon is originated by elevated blood vessel
      density or by reactive hyperemia. METHODS: Laser Doppler flow was studied in 35
      melanocytic nevi, 22 malignant melanomas and three basal cell carcinomas. After
      excision digital imaging analysis was performed in microtome sections (factor
      VIII-associated antigen and CD 31 labelled). The ratio of vessel area in
      histological sections from tumor tissue and in non-lesional skin was calculated
      and related to Doppler flow values. RESULTS: Malignant melanomas demonstrated an
      enlargement of vessel cross-sectional area by factor 3.7+/-1.9 and of Doppler
      flow by factor 10.56+/-10.7, and melanocytic nevi accomplished increase of vessel
      cross-sectional area by factor 1.7+/-0.9 and of Doppler flow by factor 2.7+/-3.5.
      CONCLUSION: The laser Doppler flow is influenced by the number and the velocity
      of erythrocytes in the tissue. The greater increase of laser Doppler flow than of
      vessel density in histological sections demonstrates that the flow signal in skin
      tumors is caused by neovascularization as well as by functional hyperemia. Laser
      Doppler perfusion imaging is a useful method for non-invasive, repeated and
      quantitative assessment of tumor vascular network and effects of antiangiogenic
      treatment directed vs. tumor vasculature in vivo, but it cannot distinguish
      between increased vessel density and reactive hyperemia.

PMID- 16420532
TI  - Sensitive skin: correlation with skin surface microrelief appearance.
AB  - BACKGROUND/PURPOSE: Sensitive skin is a condition associated with reduced
      tolerance to environmental factors and/or the application of topical products,
      such as cosmetics. Its pathophysiology has not been fully elucidated and few data
      are available on its prevalence. The aim of this study was to investigate
      possible correlation between objective sensitivity and skin surface microrelief.
      METHODS: During an epidemiological survey conducted for a campaign promoted by
      International Society of Plastic Dermatology in Italy, 243 adult healthy subjects
      of both sexes with no evident dermatological disorder but positive to the lactic
      acid stinging test, were submitted to cyanoacrylate stratum corneum stripping
      from the volar forearm for the determination of the irregularity of the skin
      surface microrelief (irregularity skin index (ISI)). RESULTS: A significant
      correlation was found between intensity of symptoms in stingers and ISI (r(s)=
      0.47; P<0.001). CONCLUSION: Sensitive skin is common in the healthy population.
      ISI can contribute towards the identification of subjects with sensitive skin and
      the development of more specific skin treatments for this prevalent condition.

PMID- 16420533
TI  - Digital camera images obtained using a light-emitting diode illuminator and their
      dermatological applications.
AB  - BACKGROUND/PURPOSE: Although digital cameras have powerful macrocapabilities,
      flash macrophotographs are often unsatisfactory. The aim of this study was to
      develop a light-emitting diode (LED) illuminator for macro digital photography
      that allows colorimetric investigations of the skin. METHODS: We devised an LED
      illuminator suitable for acquiring super-macro digital images of the skin.
      Reference CIELAB color chart values were compared statistically with computed
      values from digital images in order to obtain equations for real CIELAB values.
      Using these, we acquired and analyzed images of various dermatological conditions
      using an LED illuminator. RESULTS: The images obtained with the devised LED
      illuminator were more reproducible than flash-assisted photographs. With proper
      camera settings, the devised LED illuminator and the color analysis method
      developed during this study provided digital skin images containing colorimetric
      information. CONCLUSION: A digital camera equipped with an LED illuminator is a
      useful tool for dermatological research and clinical practice.

PMID- 16420534
TI  - Mid-infrared spectroscopy on skin using a silver halide fibre probe in vivo.
AB  - BACKGROUND/AIM: Mid-infrared spectroscopy is a versatile method for in vivo
      investigation of skin after topical treatment with skin care products. METHODS:
      FTIR-spectrometer (Bruker Optics) with a flexible silver halide fibre probe
      (Infrared Fiber Sensors). RESULTS: Absorbance spectra from 700 to 3000 cm(-1)
      have been recorded to gain information about proteins (amide-I and amide-II
      vibrations at 1650 and 1550 cm(-1)), esters (1740 cm(-1)), carboxylic acid (1710
      cm(-1)), polyalcohols (1050 cm(-1)) and hydrocarbons (CH(n) vibrations at 2800
      3000 cm(-1)). CONCLUSIONS: Using the particular light guide, we were able to
      measure for the first time the effects of lip care products on lips directly.
      Furthermore, water binding and glycerol content of the skin could be determined
      simultaneously, as well as the replenishment of lipids by lipid-enriched bath
      oil.

PMID- 16420535
TI  - Measurement of the mechanical properties of the skin using the suction test.
AB  - INTRODUCTION: The suction test is commonly used to study the mechanical
      properties of human skin in vivo. The unevenness of the stress fields complicates
      obtaining the intrinsic mechanical parameters of the skin in vivo because the
      values of the local stresses and deformations cannot be calculated directly from
      the displacements and forces applied by the test apparatus. In general, users
      only take into account the negative pressure applied and the elevation of the
      dome of skin drawn up in order to deduce the properties of the skin. This method
      has the major disadvantage of being dependent on the experimental conditions
      used: in particular, the size of the suction cup and the negative pressure
      applied. Here, we propose a full mechanical study of the test to provide rigorous
      results. We compare the frequently used geometric method (making the thin plate
      hypothesis), Timoshenko's method (which can take greater plate thicknesses into
      account) and finally various results obtained by the finite elements (FE)
      technique. METHODS: The suction test was modelled by FE with large displacements
      and large deformations both for orthotropic and isotropic plates. The results
      obtained in the elastic domain for various values of Young's modulus and of
      applied negative pressure were used as references and were compared with methods
      using analytical relationships. RESULTS: The geometric method generally used in
      the interpretation of suction tests gives results, which in certain
      configurations, are very different from those obtained by FE. The method of
      Timoshenko is suited to thick plates 'in contact' or embedded round the edge, the
      elevation of the dome and the tension and flexion stresss are analytically
      accessible through relationships involving four constants that are dependent on
      the limit conditions. Comparison with the FE results enabled the optimisation of
      the coefficients to adapt the relationships to the particular conditions of the
      suction trials. CONCLUSION: We showed the limits of the geometrical method and
      proposed a solution, which while remaining simple to use, gives results that are
      closer to reality both for the calculation of the modulus and for the
      determination of the state of the stresses obtained.

PMID- 16420536
TI  - Effect of elastic compression stockings on oedema prevention in healthy controls
      evaluated by a three-dimensional measurement system.
AB  - BACKGROUND/AIMS: The degree of oedema may differ at various sites on the leg.
      This study evaluated the degree of oedema at the calf, ankle and foot using a
      three-dimensional measurement system. METHODS: By three-dimensional measurement
      system using the grid pattern projection method, the effects of four different
      types of elastic compression stockings on oedema prevention were compared in
      healthy subjects. RESULTS: Without stockings, a significant increase in the
      circumference and volume was seen at the ankle and foot in the evening compared
      with morning values. The average increase in circumference was greater at the
      foot than that at the ankle. A significant increase in circumference and volume
      in the evening after a day without stockings disappeared when elastic compression
      stockings were worn during the day. The coefficient of variation was greater for
      measurements at the foot than for those at the calf and ankle. CONCLUSION: Oedema
      develops easily in order of the foot, the ankle and the calf in healthy
      populations. Elastic stockings, even with a pressure as low as 8 mmHg, are
      effective on oedema prevention. In measurement at the foot, further developments
      are necessary to improve this system.

PMID- 16420537
TI  - Use of the dynamic vapor sorption meter to measure skin hydration properties, in
      vitro.
AB  - BACKGROUND: Maintaining an adequate skin moisture balance is important for
      retaining soft, pliable, healthy-looking skin. This report describes the use of
      the dynamic vapor sorption (DVS) meter to quantify water content of skin in vitro
      under a variety of conditions. It is the only instrument that couples an ultra
      sensitive Cahn microbalance (resolution=0.1 microg) with an environmental system
      where both humidity and temperature are controlled. This feature is important
      since the skin's water content is influenced by changes in the relative humidity.
      METHOD: In every experiment, the temperature was held constant at 25 degrees C,
      and the starting relative humidity (RH) was set to 0% RH. The RH was programmed
      to step in 10% increments ending at 90% RH. The RH was incremented to the next
      level only when the mass change was less than 0.005%/min. RESULTS: A hysteresis
      was observed for all skin sorption/desorption experiments completed. Glycerin and
      the sodium salt of pyrrolidone carboxylic acid (NaPCA) both enhanced the % water
      content of skin. NaPCA was a more effective humectant at high relative humidities
      (above 60% RH); while glycerin performed better at humidities below 40% RH.
      Washing the skin with sodium lauryl sulfate (SLS) reduced the skin's ability to
      absorb water more so than washing with Tween 80, a milder surfactant. Vaseline
      petroleum jelly enhanced the water-retention properties of untreated skin.
      CONCLUSIONS: The DVS can effectively be used to study the sorption and desorption
      properties of skin. We have shown that the amount of water absorbed is influenced
      by the RH, the presence of humectants and/or occlusive agents, and surfactant
      harshness.

PMID- 16420538
TI  - Effect of dermal thickness, tissue composition, and body site on skin
      biomechanical properties.
AB  - BACKGROUND/PURPOSE: Quantitative measurement of skin biomechanical properties has
      been used effectively in the investigation of physiological changes in tissue
      structure and function and to determine treatment efficacy. As the methods are
      applied to new questions, tissue characteristics that may influence the resultant
      biomechanical properties are important considerations in the research design. For
      certain applications, variables such as dermal thickness and subdermal tissue
      composition, as well as age and/or solar exposure, may influence the skin
      biomechanics. METHODS: We determined the influence of dermal thickness, tissue
      composition, and age on the skin biomechanical properties at the shoulder, thigh,
      and calf among 30 healthy females. We compared two devices, the Biomechanical
      Tissue Characterization System and the Cutometer SEM 575 Skin Elasticity Meter ,
      to determine the effect of tissue sampling size. Dermal thickness was measured
      with 20 MHz ultrasound (Dermascan C) and tissue composition was inferred from
      anthropomorphic data. RESULTS: Skin thickness was significantly correlated with
      stiffness, energy absorption, and U(r)/U(f) for the shoulder. Body mass index
      (BMI) was significantly correlated with stiffness (negative correlation), energy
      absorption (positive), and skin thickness (negative) for the shoulder.
      Significant differences across body sites were observed. The calf was
      significantly different from the thigh and shoulders for all parameters (P<0.05,
      one-way anova). The calf had significantly lower laxity, laxity%, elastic
      deformation, energy absorption, elasticity, elasticity %, U(r), U(f), and
      U(r)/U(f) and significantly higher stiffness compared with the thighs and
      shoulders. sites. The thigh and shoulder sites were significantly different for
      all parameters except U(r)/U(f), elasticity %, laxity%, and stiffness. The
      dominant and non-dominant sides were significantly different. The dominant side
      (right for 90% of the subjects) had increased stiffness and decreased energy
      absorption (tissue softness, compliance) compared with the left side. A
      significant (P< or =0.02) negative relationship with age was seen for all
      biomechanical measures except stiffness at the shoulder. For the thigh and calf
      sites, significant negative correlations with age were found for elasticity %,
      U(r), and U(r)/U(f). Age and skin thickness were not correlated in this
      population. Skin thickness and age influenced the energy absorption at the
      shoulder site. The biological elasticity at the calf site could be predicted by
      age and BMI. The biological activity at the thigh site could be predicted by skin
      thickness and BMI. CONCLUSIONS: Significant regional variations in biomechanical
      properties and dominant side effects were observed. The biomechanical properties
      were significantly influenced by age. Certain properties varied with dermal
      thickness and tissue composition. The parameters were well correlated between the
      two instruments. The Cutometer, with its smaller aperture, was found to be more
      sensitive to age relationships.

PMID- 16420539
TI  - High-resolution ultrasound reflex transmission imaging and digital photography:
      potential tools for the quantitative assessment of pigmented lesions.
AB  - BACKGROUND/AIMS: High-resolution ultrasound (HRU) is a relatively cheap imaging
      method that shows small quantitative differences between benign naevi and
      melanoma. Previous studies using B-mode display suggest that these arise from
      their differing attenuating properties. Attenuation characteristics, however, are
      better evaluated using reflex transmission imaging (RTI). White light clinical
      (WLC) photography is an even cheaper imaging method that is routinely used for
      monitoring but less frequently in everyday diagnosis. As features from each
      method may have an independent origin, two such modalities may be of greater
      diagnostic value than either method alone. However, although quantitative
      analysis of digital photographs is being developed to aid tumour diagnosis, in
      vivo RTI for the evaluation of pigmented skin lesions has not previously been
      described. This paper presents the feasibility of performing RTI in vivo and
      evaluates the reliability of the objective features used. The potential of the
      combination of quantitative RTI and white light (WL) digital photography data for
      the classification of pigmented lesions was assessed. METHODS: Randomly selected
      patients were recruited via a skin cancer screening clinic. RTI data were
      acquired from each index lesion with a 20 MHz single-element scanner. WL images
      were taken using a high-resolution (2.8 Mpixels) digital camera. Quantitative
      features calculated from both images were used to derive a discriminant rule.
      This equation was then applied to reclassify each case based on its quantitative
      criteria. The resultant classification was compared with histological diagnosis.
      RESULTS: Twenty-four lesions (10 melanoma and 14 naevi) were studied. On RTI, no
      subjective differences were observed between benign naevi and melanoma. Many
      lesions were either not visible on RTI or lacked clearly definable borders.
      Consequently, the WL photographs were used to draw lesion boundaries on RT images
      for feature calculation. Melanoma were less attenuating than naevi on RTI
      (P=0.026) and had greater red colour variegation on WL imaging (P=0.016). The
      combination of quantitative parameters (two from RTI and four from photographs)
      improved sensitivity for this sample without compromising the specificity of 100%
      compared with either modality alone. The procedure is highly reproducible (r=0.85
      between two operators). CONCLUSIONS: Pigmented skin lesions can be quantitatively
      defined from RTI data acquired in vivo and a significant difference in
      attenuation is shown. However, accurate registration of the RT image with a
      corresponding photograph was crucial for this purpose and only possible when
      corresponding points could be reliably identified on both images. Combination of
      features from ultrasound and optical images may synergistically improve
      diagnostic accuracy and a larger study is warranted to investigate this.

PMID- 16420540
TI  - The hairless guinea-pig as a model for treatment of cumulative irritation in
      humans.
AB  - BACKGROUND: The effect of six skin-care formulations (SCFs) on experimentally
      induced cumulative irritation was studied in hairless guinea-pigs (HLGPs) and in
      human volunteers (HVs). The formulations were a basic cream, a carbomer cream and
      four modifications of the carbomer cream, containing either 10% isopropyl
      palmitate (IPP cream), 10% glycerol (glycerol cream), 19.5% canola oil (canola
      oil cream) or 0.5% (-)-alpha-bisabolol (bisabolol cream). METHODS: In HLGP,
      irritant dermatitis was induced with 30 min daily exposure for 4 days to 0.5%
      sodium lauryl sulfate aq. (SLS). In HVs, irritant dermatitis was induced with 10
      min daily exposure for 5+4 days (no irritation on weekends) to 3% SLS aq. on the
      right and 30% nonanoic acid (NON) in n-propanol on the left volar forearm.
      Clinical scoring was performed daily; evaporimetry (total epidermal water loss
      (TEWL)), hydration and colorimetry were measured at baseline (day 0) in the
      middle and at the end of treatment. Treatments were applied twice daily. The
      basic cream and the IPP cream were excluded from testing in HLGP because they
      were known from previous studies to be irritant in HLGP, while all formulations
      were known to be equally and well tolerated locally in humans. RESULTS: All
      formulations worsened the skin irritation in HLGP: the glycerol cream the least,
      the canola oil cream the most, while the bisabolol cream and the carbomer cream
      were indistinguishable. In humans, the glycerol cream was better than 'No
      Treatment' after cumulative irritation with both SLS and NON. The basic cream was
      better tolerated in humans than was expected from previous testing in HLGPs.
      CONCLUSION: In conclusion, the results from the studies in HLGPs and HVs are in
      agreement with regard to ranking of the SCFs. Further, the glycerol cream showed
      a positive treatment effect on both SLS- and NON-irritated skin in HVs.

PMID- 16420541
TI  - The difference between the constitutive and facultative skin color does not
      reflect skin phototype in Asian skin.
AB  - BACKGROUND/PURPOSE: The assessment of the sensitivity of human skin to
      ultraviolet (UV) radiation is important in the area of phototherapy,
      photodermatoses, photo-aging, photo-carcinogenesis, and photo-protection. Some
      reports have shown that quantitatively measured skin color is a good indicator
      for predicting UV sensitivity to human skin in Caucasians. In this study, our aim
      was to define the correlation between skin color and the skin phototype assessed
      by the Fitzpatrick method in Asian brown skin. METHODS: A total of 180 medical
      students with similar life styles were included in this study. Their skin
      phototype was classified according to the system introduced by Fitzpatrick. Then,
      using a Minolta Spectrophotometer CM-2002, their skin color was determined on the
      buttocks and forehead. The buttock color was taken as the constitutive skin
      color, and the forehead color as the facultative skin color. Using these measured
      values, we compared the skin color with the skin phototype to find their
      correlation. Also, we investigated whether the difference between the
      constitutive and facultative skin colors of each individual had a relationship
      with his or her skin phototype. RESULTS: The constitutive skin color became
      darker with increasing skin phototype, and this change was statistically
      significant. As for the facultative skin color, it also became darker with
      increasing skin phototype, but was less well correlated with the skin phototype
      than the constitutive skin color. However, the difference between the
      constitutive and facultative skin colors did not show consistent results in
      predicting the skin phototype. CONCLUSION: In this study, we found that the
      constitutive skin color can be a good indicator of the skin phototype. However,
      the difference between the constitutive and facultative skin colors of each
      individual does not give any meaningful information for the assessment of his or
      her skin phototype in Asian skin.

PMID- 16420542
TI  - Acupuncture--a critical analysis.
AB  - Even though widely used in today's clinical practice, acupuncture has remained a
      controversial subject. Many reviews are currently available but most lack a
      critical stance and some are overtly promotional. The aim of this overview is to
      provide a balanced, critical analysis of the existing evidence. Some of the
      original concepts of traditional acupuncture are not supported by good scientific
      evidence. Several plausible theories attempt to explain how acupuncture works but
      none are proved beyond doubt. The clinical effectiveness of acupuncture continues
      to attract controversy. Many controlled clinical trials and numerous systematic
      reviews of these studies have been published. Considerable problems are
      encountered when interpreting these data. Heterogeneity is a significant drawback
      of both clinical trials and systematic reviews. Some of the controversies may be
      resolved through the use of the new 'placebo needles' which enable researchers to
      adequately control for placebo effects of acupuncture. The majority of studies
      using such devices fails to show effects beyond a placebo response. Acupuncture
      has been associated with serious adverse events but most large-scale studies
      suggest that these are probably rare. Nonserious adverse effects occur in 7-11%
      of all patients. In conclusion, acupuncture remains steeped in controversy. Some
      findings are encouraging but others suggest that its clinical effects mainly
      depend on a placebo response.

PMID- 16420543
TI  - Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune
      implications in critical illness.
AB  - Traumatic injury, surgical interventions and sepsis are amongst some of the
      clinical conditions that result in marked activation of neuroendocrine and opiate
      responses aimed at restoring haemodynamic and metabolic homeostasis. The central
      activation of the neuroendocrine and opiate systems, known collectively as the
      stress response, is elicited by diverse physical stressor conditions, including
      ischaemia, glucopenia and inflammation. The role of the hypothalamic-pituitary
      adrenal axis and sympathetic nervous system in counterregulation of haemodynamic
      and metabolic alterations has been studied extensively. However, that of the
      endogenous opiates/opioid system is still unclear. In addition to activation of
      the opiate receptor through the endogenous release of opioids, pharmacotherapy
      with opiate receptor agonists is frequently used for sedation and analgesia of
      injured, septic and critically ill patients. How this affects the haemodynamic,
      cardiovascular, metabolic and immune responses is poorly understood. The variety
      of opiate receptor types, their specificity and ubiquitous location both in the
      central nervous system and in the periphery adds additional complicating factors
      to the clear understanding of their contribution to the stress response to the
      various physical perturbations. This review aims at discussing scientific
      evidence gathered from preclinical studies on the role of endogenous opioids as
      well as those administered as pharmacological agents on the host cardiovascular,
      neuroendocrine, metabolic and immune response mechanisms critical for survival
      from injury in perspective with clinical observations that provide parallel
      assessment of relevant outcome measures. When possible, the clinical relevance
      and corresponding scenarios where this evidence can be integrated into our
      understanding of the clinical implications of opiate effects will be examined.
      Overall, the scientific basis to enhance clinical judgment and expectations when
      using opioid sedation and analgesia in the management of the injured, septic or
      postsurgical patient will be discussed.

PMID- 16420545
TI  - Survival rate 28 days after hospital admission with first myocardial infarction.
      Inverse relationship with socio-economic circumstances.
AB  - OBJECTIVE: To study to what extent geographical differences of the mortality from
      ischaemic heart disease (IHD) can be accounted for by the 28-day case fatality
      rate (CFR) following first hospital admittance for acute myocardial infarction
      (MI) and whether the geographical pattern of survival has any relationship with
      socio-economic circumstances. DESIGN: Register-based surveillance study. SETTING:
      Seventeen residential areas in Malmo, Sweden. SUBJECTS: All 5533 patients were
      admitted during 1986-1995 for a first acute MI at Malmo University Hospital. Main
      outcome measures. CFR is based on record linkage with national registers. Area
      specific cardiovascular and socio-economic scores (SES) are based on previous
      cross-sectional studies. RESULTS: In patients below 75 years of age, differences
      of the 28-day CFR accounted for 20-30% of the geographical variance in mortality
      from IHD. No corresponding association was found in older age groups. Patients
      from areas with low SES had the highest CFR, 23.8%. The odds ratios of fatal
      outcome for patients from areas with median and low SES (versus high SES) were
      1.23 (95% CI: 1.01-1.50) and 1.25 (95% CI: 1.03-1.52), respectively (P for trend:
      0.060). The strongest correlation was observed in men below 75 years of age (P
      for trend: 0.007). During the study period there was an improvement of the
      survival rate for patients from high and medium SES areas but no corresponding
      change for patients coming from areas having a low SES. CONCLUSIONS: In patients
      below 75 years, geographical differences of the mortality from IHD were related
      to differences of the 28-day CFR following hospital admittance for a first MI.
      Rates of survival were inversely related to socio-economic circumstances in the
      patient's residential area.

PMID- 16420544
TI  - Discordant twin growth in utero and differences in blood pressure and endothelial
      function at 8 years of age.
AB  - OBJECTIVE: Low birth weight is associated with increased prevalence of
      hypertension and cardiovascular disease in adults. The aim of this study was to
      evaluate genetic and intrauterine environmental contributions to blood pressure
      (BP) and vascular functions in twins with discordant growth in utero. SUBJECTS:
      We studied 31 twin pairs (21 monozygous and nine dizygous), mean age 8 years)
      with large within-pair differences in birth weight. Among the monozygous pairs,
      nine had suffered from twin-to-twin-transfusion syndrome (TTTS). METHODS: Apart
      from BP, we determined diameters and elasticity of the carotid artery and
      abdominal aorta with ultrasonography, and endothelial function in skin vessels
      with a laser Doppler technique, before and after transdermal delivery of
      acetylcholine and nitroglycerin. RESULTS: Eight of 62 twin subjects had a
      systolic BP above the 90th percentile in a North-American reference population.
      Among these, seven/eight were monozygous with a history of poor fetal growth
      and/or TTTS. In monozygous twin pairs without TTTS, systolic BP and pulse
      pressure were higher and vascular endothelial function was impaired in the lower
      birth weight twin. In the TTTS group, the lighter twin had a narrower carotid
      artery but there was no within-pair difference in arterial elasticity. Pre
      eclampsia during the index pregnancy enhanced within-pair differences in BP but
      abolished within-pair differences in endothelial function. CONCLUSIONS: Severe
      fetal growth retardation contributes to higher BP, arterial narrowing and
      endothelial dysfunction in childhood. Pre-eclampsia may act both as an effect
      modifier and confounder of these associations.

PMID- 16420546
TI  - Temporal trends in the prescription of vitamin K antagonists in patients with
      atrial fibrillation.
AB  - OBJECTIVES: Anticoagulation therapy is recommended in patients with atrial
      fibrillation (AF) and risk factors for stroke. We studied the temporal trends in
      the prescription of vitamin K antagonists (VKA) in patients with a first hospital
      diagnosis of AF in Denmark, 1995-2002. DESIGN: The Danish National Hospital
      Registry was used to identify subjects with a first hospital diagnosis of AF and
      the Danish Register of Medical Products Statistics to determine the proportion of
      these patients who claimed a prescription of VKA within 3 months from discharge.
      RESULTS: Amongst 68 546 patients aged 50-99 years with a diagnosis of AF who
      survived 3 months following discharge, 24 991 (36%) patients claimed a
      prescription of VKA within 3 months. In both men and women a gradual increase in
      the use of VKA with time was observed, the relative increase being largest
      amongst the 80- to 99-year olds. In all age groups, the prescription of VKA was
      lower in women than in men, including patients with a prior or concurrent stroke.
      CONCLUSIONS: From 1995 to 2002 the proportion of AF patients receiving VKA
      therapy increased significantly but the use of VKA therapy amongst women was
      lagging behind that of men. Even in patients with AF and prior stroke, the use of
      VKA seems to be less than optimal.

PMID- 16420548
TI  - Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic
      primary hyperparathyroidism.
AB  - OBJECTIVES: Patients with mild primary hyperparathyroidism (pHPT) often appear
      asymptomatic, and have previously been regarded as not requiring treatment.
      However, increased cardiovascular morbidity and dyslipidaemia have also been
      recognized in mild pHPT, which also seem to be normalized after
      parathyroidectomy. The present study explores whether postmenopausal women with
      mild pHPT have decreased bone mineral density (BMD) compared with age-matched
      healthy controls, and the effects on BMD of parathyroidectomy. DESIGN, SUBJECTS
      AND INTERVENTION: A population-based health screening of 5202 postmenopausal
      women identified 87 overtly asymptomatic patients with mild pHPT as well as age
      matched healthy controls. A 5-year follow-up included 49 cases who had undergone
      parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar
      spine and the total body. RESULTS: At study entry, BMD was 5-6% lower in the
      lumbar spine (L2-L4) and femoral neck in cases compared with matched controls.
      After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the
      parathyroidectomized cases and remained stable in the femoral neck. However,
      femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the
      cohort). CONCLUSION: In accordance with recent NIH guidelines for pHPT treatment,
      the level of BMD per se in the investigated group of patients justifies
      parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be
      expected to increase BMD in L2-L4 to the level of the controls, to increase
      femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in
      the elderly population.

PMID- 16420547
TI  - Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia
      when added to the standard treatment: a prospective and randomized clinical trial
      of 381 patients.
AB  - OBJECTIVES: To study whether levofloxacin, added to standard treatment, could
      reduce the high mortality and complication rates in Staphylococcus aureus
      bacteraemia. DESIGN: A prospective randomized multicentre trial from January 2000
      to August 2002. SETTING: Thirteen tertiary care or university hospitals in
      Finland. SUBJECTS: Three hundred and eighty-one adult patients with S. aureus
      bacteraemia. Patients with meningitis, and those with fluoroquinolone- or
      methicillin-resistant S. aureus were excluded. INTERVENTIONS: Standard treatment
      (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n
      = 191). Supplementary rifampicin was recommended if deep infection was suspected.
      MAIN OUTCOME MEASURES: Primary end-points were mortality at 28 days and at 3
      months. Clinical and laboratory parameters were analysed as secondary end-points.
      RESULTS: Adding levofloxacin to the standard treatment offered no survival
      benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the
      standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin
      combination did not differ from the standard treatment in the number of
      complications, time to defervescence, decrease in serum C-reactive protein
      concentration or length of antibiotic treatment. Deep infection was found in 84%
      of patients within 1 week following randomization with no difference between the
      treatment groups. At 3 months, the case fatality rate for patients with deep
      infection was 17% amongst those who received rifampicin versus 38% for those
      without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69
      5.54). CONCLUSIONS: Levofloxacin combined with standard treatment in S. aureus
      bacteraemia did not decrease mortality or the incidence of deep infections, nor
      did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia
      appeared to be more common than previously reported.

PMID- 16420549
TI  - Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine
      in healthy postmenopausal women: a randomized, placebo-controlled study.
AB  - OBJECTIVE: To compare the effects of oral and transdermal hormone therapy (HT) on
      asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide
      synthase, in postmenopausal women. DESIGN: In a multicentre, placebo-controlled,
      double-blind study, 152 hysterectomized healthy women were randomized to receive
      daily transdermal 17beta-oestradiol (tE2, n = 33), or oral micronized 17beta
      oestradiol either unopposed (oE2, n = 37), or continuous combined with gestodene
      (oE2 + G, n = 33), or placebo (n = 49) for 13, 28-day treatment cycles. Plasma
      concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were
      measured at baseline and in treatment cycles 4 and 13 with a high-performance
      liquid chromatography method. RESULTS: After 13 cycles all active treatment
      groups showed a significant reduction in ADMA compared with placebo: tE2, -4.0%
      (95% CI: -7.5 to -0.6%); oE2, -7.7% (95% CI: -10.9 to -4.4%) and oE2 + G, -7.5%
      (95% CI: -10.8 to -4.3%). ancova showed a significantly larger reduction in the
      oral groups compared with the transdermal group (tE2 vs. oE2 and tE2 vs. oE2 + G,
      both P < 0.01). Oral, but not transdermal treatment, significantly reduced
      arginine compared with placebo. All active treatments reduced SDMA; however, this
      was only statistically significant in the oE2 group. CONCLUSION: Reduction of
      ADMA was more pronounced after oral than after tE2 administration. Adding
      gestodene to oral 17beta-oestradiol did not alter the reduction of ADMA. The
      clinical implications of these findings remain uncertain; however, the decrease
      of ADMA by 17beta-oestradiol could be a key phenomenon in the modulation of
      nitric oxide synthesis by postmenopausal HT.

PMID- 16420551
TI  - A forgotten aetiology of acute hepatitis in immunocompetent patient: syphilitic
      infection.

PMID- 16420550
TI  - Intra-abdominal abscess in a patient with tumour necrosis factor receptor
      associated periodic syndrome.
AB  - Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an
      autoinflammatory disorder characterized by periodic attacks of fever and
      inflammation, due to mutations in the gene coding for the TNF type I receptor
      (TNFRSF1A). A 16-year-old patient with the diagnosis of TRAPS was admitted to
      hospital because of fever and abdominal pain. Initially, the symptoms were
      interpreted as manifestations of another TRAPS attack, but the patient's
      condition worsened, despite treatment with corticosteroids and antibiotics. A
      repeated computer tomography revealed an intra-abdominal abscess, which
      necessitated urgent surgical intervention. This case stresses the importance of
      differential diagnostic vigilance when dealing with patients with rare genetic
      diseases.

PMID- 16420552
TI  - The use of B-type natriuretic peptide in the management of elderly patients with
      acute dyspnoea ( J Intern Med 2005;258:77-85).

PMID- 16420554
TI  - International consensus statement on an update of the classification criteria for
      definite antiphospholipid syndrome (APS).
AB  - New clinical, laboratory and experimental insights, since the 1999 publication of
      the Sapporo preliminary classification criteria for antiphospholipid syndrome
      (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh
      International Congress on antiphospholipid antibodies. In this document, we
      appraise the existing evidence on clinical and laboratory features of APS
      addressed during the forum. Based on this, we propose amendments to the Sapporo
      criteria. We also provide definitions on features of APS that were not included
      in the updated criteria.

PMID- 16420555
TI  - Are B vitamins a risk factor for venous thromboembolism? Yes.

PMID- 16420556
TI  - Are B vitamins a risk factor for VTE? Perhaps.
AB  - Venous thrombosis is considered as a multicausal disease. Hyperhomocysteinemia is
      considered as one of the risk factors for venous thrombosis. Because homocysteine
      levels are strongly influenced by the intake and concentrations of B vitamins, it
      is worthwhile to assess the role of these vitamins as a risk factor for venous
      thrombosis.

PMID- 16420557
TI  - Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet
      disorders and platelet function.
AB  - BACKGROUND: Closure time (CT), measured by platelet function analyzer (PFA-100)
      device, is now available to the clinical laboratory as a possible alternative or
      supplement to the bleeding time test. AIM: On behalf of the Platelet Physiology
      Subcommittee of the Scientific and Standardization Committee of the International
      Society on Thrombosis and Haemostasis (ISTH-SSC), a working Group was formed to
      review and make recommendations on the use of the PFA-100 CT in the evaluation of
      platelet function within the clinical laboratory. METHODS: The Medline database
      was searched to review the published information on the PFA-100 CT in the
      evaluation of platelet disorders and platelet function. This information, and
      expert opinion, was used to prepare a report and generate consensus
      recommendations. RESULTS: Although the PFA-100 CT is abnormal in some forms of
      platelet disorders, the test does not have sufficient sensitivity or specificity
      to be used as a screening tool for platelet disorders. A role of the PFA-100 CT
      in therapeutic monitoring of platelet function remains to be established.
      CONCLUSIONS: The PFA-100 closure time should be considered optional in the
      evaluation of platelet disorders and function, and its use in therapeutic
      monitoring of platelet function is currently best restricted to research studies
      and prospective clinical trials.

PMID- 16420558
TI  - Protease nexin-1: a regulator of vascular disease?

PMID- 16420559
TI  - The serpin protease nexin-1 regulates vascular smooth muscle cell adhesion,
      spreading, migration and response to thrombin.
AB  - BACKGROUND: Protease nexin-1 (PN-1) is an important physiological regulator of
      thrombin in the brain. PN-1 is also present in aortic smooth muscle cells and may
      thus participate in vascular biology. However, little is known about its function
      in the vessel wall. OBJECTIVES: In this study, we investigated the effect of PN-1
      overexpression in smooth muscle cells (SMCs), on their sensitivity to thrombin,
      and their capacity for adhesion, spreading and migration. RESULTS: Two clones
      exhibiting a two- to threefold increase in PN-1 expression were selected and
      compared with untransfected and mock-transfected cells. Overexpression of PN-1
      was observed to inhibit thrombin-induced cell responses as indicated by a twofold
      decrease in induction of PAI-1 expression, a decreased calcium mobilization in
      response to low thrombin concentrations and a twofold increase in the capacity to
      inhibit thrombin catalytic activity. Overexpression of PN-1 did not modify
      adhesion, spreading, and migration of SMCs on type I collagen. In contrast, SMCs
      overexpressing PN-1 exhibited a 40% reduction in adhesion, a 50% reduction in
      spreading and a complete absence of migration on vitronectin when compared with
      control SMCs. CONCLUSIONS: Our studies thus reveal that PN-1 is likely to play a
      critical role in regulating essential cell functions such as (i) thrombin-induced
      responses, which are dependent on its antiprotease activity, and (ii) adhesion,
      spreading, and migration, which are independent of its antiprotease activity and
      may be related to its interaction with other partners, such as vitronectin in the
      present case.

PMID- 16420560
TI  - Attack of the acronyms: TTP, VWF, ADAMTS-13 and SELDI-TOF-MS.

PMID- 16420561
TI  - A rapid test for the diagnosis of thrombotic thrombocytopenic purpura using
      surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF)-mass
      spectrometry.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a life-threatening
      thrombotic microangiopathy, requires immediate diagnosis and plasma exchange
      therapy. Development of TTP is related to functional deficiency of ADAMTS-13
      protease that leads to the accumulation of ultra large von Willebrand factor
      (VWF) and subsequent platelet thrombosis. Currently no clinical test is available
      for the rapid detection of ADAMTS-13 activity. OBJECTIVES: The goal is to devise
      a novel method to rapidly detect functional activity of ADAMTS-13 and improve
      clinical outcome. METHODS AND RESULTS: A recombinant VWF substrate containing the
      ADAMTS-13 cleavage site and a 6X Histidine tag was cleaved by ADAMTS-13 in a dose
      dependent manner, generating approximately 7739 Da peptide containing a 6X
      Histidine tag. This cleaved peptide, bound to an IMAC/Nickel ProteinChip, was
      quantified using Surface Enhanced Laser Desorption/Ionization Time-of-flight Mass
      Spectrometry (SELDI-TOF-MS). The assay is capable of quantifying ADAMTS-13
      activity as low as 2.5% in plasma within 4 h. When the cleaved peptide was
      quantified as a ratio of an internal control peptide, the test displayed good
      reproducibility, with an average inter-assay coefficient of variation (CV) of <
      33%. Further validation revealed a mean ADAMTS-13 activity of 92.5% +/- 16.6% in
      39 healthy donors. Sixteen patients with idiopathic TTP displayed mean ADAMTS-13
      activity of 1.73% +/- 3.62%. Further utility of this novel method includes
      determining the inhibitory titer of ADAMTS-13 antibody in cases of acquired TTP.
      CONCLUSIONS: We have devised a novel SELDI-TOF-MS assay that offers a rapid, cost
      effective, and functionally relevant test for timely diagnosis and management of
      TTP.

PMID- 16420562
TI  - When is cardiovascular genomics delivering on its promise?

PMID- 16420563
TI  - Multi-locus candidate gene polymorphisms and risk of myocardial infarction: a
      population-based, prospective genetic analysis.
AB  - BACKGROUND: Polymorphisms in candidate genes related to lipid metabolism,
      thrombosis, hemostasis, cell-matrix adhesion, and inflammation have been
      suggested clinically useful in risk assessment of cardiovascular disease.
      METHODS: We evaluated a panel of 92 candidate gene polymorphisms, using a
      multiplex polymerase chain reaction-immobilized probe assay amongst 523
      individuals who subsequently developed myocardial infarction (MI), and amongst
      2092 individuals who remained free of reported cardiovascular disease over a mean
      follow-up period of 13.2 years. RESULTS: Of the 92 polymorphisms tested, three
      that we previously reported on were associated with risk of MI, [pro12ala in the
      peroxisome proliferator activated-receptor gamma gene (odds ratio, OR = 0.75, P =
      0.02); thr164ile in the beta-2 adrenergic receptor gene (OR = 0.14, P = 0.007);
      and ala23thr polymorphism in the eotaxin gene (OR = 1.87, P = 0.01)]. However,
      when adjusted for the other 89 polymorphisms evaluated, these findings were no
      longer statistically significant. Further, in contrast to reports from other
      investigators, we found little evidence for association of a C677T polymorphism
      in the 5,10-methylenetetrahydrofolate reductase gene, the angiotensin-I
      converting enzyme 1 insertion/deletion polymorphism, a 4G/5G polymorphism in the
      serine/cysteine proteinase inhibitor-clade E-member 1 gene, the factor V Leiden
      mutation, the G20210A factor II mutation, a -455G>A polymorphism in the beta
      fibrinogen gene, the cys112arg/arg158cys apolipoprotein E gene polymorphism, a
      gly460trp polymorphism in the alpha-adducin gene, and a -629C>A polymorphism in
      the cholesteryl ester transfer protein gene with risk of MI. CONCLUSIONS: After
      correction for multiple comparisons, the addition of genetic information observed
      in the present study had little impact on risk prediction models for MI. The
      present investigation highlights the importance of replication and validation of
      findings from genetic association studies.

PMID- 16420564
TI  - Comparative RNA expression analyses from small-scale, single-donor platelet
      samples.
AB  - BACKGROUND: Comparisons of platelet RNAs could provide crucial information on
      platelet function, thrombopoiesis and the etiology of megakaryocyte (MK) or
      platelet disorders. OBJECTIVES: We developed a method for stringent purification
      of platelets from small blood samples from single donors. Purity of the platelet
      preparations was verified by an RT-PCR assay. We tested three methods to identify
      the differences in RNA between platelet sources. METHODS: Differential
      hybridization to cDNA macro-arrays and suppressive-subtractive hybridization PCR
      (SSH-PCR) were used to compare RNAs from normal platelets to those from a Bernard
      Soulier syndrome (BSS) patient. Affymetrix GeneChip U133 plus 2.0 arrays were
      used to compare male and female platelet RNAs. RESULTS: Macroarrays identified
      approximately 7500 platelet transcripts, but failed to identify differentially
      expressed transcripts with confidence. SSH-PCR produced libraries almost
      exclusively of mitochondrial-derived transcripts, but included nuclear-encoded
      genes that could not be confirmed by immunoblotting of normal and BSS platelet
      lysates. The Affymetrix platform gave reproducible profiles from our small-scale
      purified platelet preparations, whereas a partially purified platelet preparation
      produced a drastically skewed transcript profile. The microarray analysis
      identified the heparanase precursor transcript as overexpressed in female
      platelets, and we observed variable yet consistently higher levels of heparanase
      protein in female platelets compared with male platelets in four independent
      donor pairs. CONCLUSIONS: This demonstrates for the first time that differential
      platelet transcript levels can identify changes in expression level of platelet
      proteins. Combined with our small-scale platelet preparation method, this
      establishes a system to compare platelets from the limited clinical sources to
      help elucidate molecular bases for platelet or megakaryocyte pathologies.

PMID- 16420565
TI  - Factor VIII and von Willebrand factor changes after desmopressin and during
      pregnancy in type 2M von Willebrand disease Vicenza: a prospective study
      comparing patients with single (R1205H) and double (R1205H-M740I) defect.
AB  - BACKGROUND: Type 2M von Willebrand disease (VWD) Vicenza is characterized by the
      presence of ultra-large von Willebrand factor (VWF) multimers in plasma and very
      low factor VIII (FVIII)/VWF measurements. So far, R1205H mutation, alone or
      associated with M740I defect, has been constantly detected in these patients. No
      data on FVIII/VWF changes after desmopressin and during pregnancy in patients
      with phenotypic VWD Vicenza has been reported. OBJECTIVE: To evaluate biological
      responsiveness to desmopressin, the FVIII/VWF changes during pregnancy and the
      clinical outcome in pregnancies and deliveries of six primipara with type 2M VWD
      Vicenza prospectively followed. PATIENTS AND METHODS: Three women with single
      (R1205H) and three with double (R1205H and M740I) mutation in the VWF gene were
      enrolled in the study. Prior to pregnancy, all patients had undergone
      desmopressin test-infusion to assess biological responsiveness and its possible
      clinical usefulness. RESULTS: The results of test-infusion with desmopressin
      showed the full normalization of FVIII/VWF measurements, with rapid clearance of
      all moieties postinfusion. However, FVIII/VWF measurements in patients with
      double defect remained greater after 4 h than those of patients with single
      defect. The severely reduced basal FVIII/VWF measurements did not change during
      pregnancy, although somewhat higher VWF levels were observed in patients with
      double defect. Five out of six women underwent successful delivery under
      desmopressin prophylaxis, without immediate or delayed bleeding and only one was
      given a FVIII/VWF concentrate because of a cesarean section. CONCLUSIONS:
      Delivery in women with VWD type 2M Vicenza is safely managed by using
      desmopressin, despite the fact that basal low FVIII/VWF is not significantly
      increased during the pregnancy.

PMID- 16420566
TI  - Activated protein C resistance -- in the absence of factor V Leiden -- and
      pregnancy.
AB  - BACKGROUND: Activated protein C (APC) resistance with or without factor V Leiden
      (FVL) is a major risk factor for venous thromboembolism. Many previous pregnancy
      studies have been focused on APC resistance caused by FVL. Very few have
      investigated APC resistance in the absence of FVL (APCR(FVL-)). MATERIAL AND
      METHODS: In a prospective study of 2480 unselected gravidae, blood was drawn in
      early pregnancy (mean = 12 weeks of gestation). APC resistance was analyzed by an
      APTT-based method (Coatest) APC-resistance) and the presence of FVL was
      determined by PCR. The APCR(FVL-) group had similar mean APC resistance ratio as
      the heterozygous carriers of FVL. The analyses were carried out no earlier than 3
      months after delivery when all data were recorded. Small-for-gestational age
      (SGA) was used as a proxy for intrauterine growth restriction. RESULTS: When
      compared with the control group, women with APCR(FVL-) had no increased risk of
      SGA, pre-eclampsia, first trimester fetal loss or venous thromboembolism.
      However, they had an increased risk of second trimester fetal loss (7.3% vs.
      2.7%, P = 0.01), and a tendency of being overweight (17.3% vs. 12.6%, P = 0.19)
      and of delivering extremely preterm (2.8% vs. 1.0%, P = 0.11). CONCLUSION: Women
      with APC resistance not caused by FVL were not at increased risk for SGA, pre
      eclampsia, first trimester fetal loss, or abnormal blood loss. However, they
      showed an increased prevalence of second trimester fetal loss.

PMID- 16420567
TI  - A prospective randomized trial of high and standard dosages of recombinant factor
      VIIa for treatment of hemarthroses in hemophiliacs with inhibitors.
AB  - AIM: A multicenter randomized open-label crossover prospective trial was designed
      to compare the efficacy, safety, and cost of standard and high dosages of
      recombinant factor VIIa (rFVIIa) for home treatment of hemarthroses in
      hemophiliacs with inhibitors. METHODS: Patients were instructed to treat, within
      6 h from the onset of bleeding, four consecutive hemarthroses of ankles, knees,
      or elbows, either with the rFVIIa standard dose of 90 microg kg(-1) (repeated as
      necessary every 3 h) or with a single high dose of 270 microg kg(-1). Patients
      who did not achieve a clinical success within 9 h continued rFVIIa treatment with
      repeated standard doses. Response to treatment was assessed for up to 48 h by
      patients/caregivers, who reported on a Visual Analogue Scale (VAS) graded from 0
      to 100 the improvement in symptoms and also rated the responses as effective,
      partially effective or ineffective. Success was defined a treatment course rated
      as effective and with a VAS score > or =70 and failure a treatment course rated
      as ineffective and VAS score < or =30, whereas treatment courses that did not
      fulfill these criteria were considered partial responses. RESULTS: Twenty
      hemophiliacs with inhibitors were originally enrolled (median age: 27 years), 18
      of them treated 32 hemarthroses assigned to the standard-dosage and 36 to the
      high-dosage regimen, during the study period of 18 months. Forty-eight
      hemarthroses (71%) occurred in target joints. Success rates for standard- and
      high-dosage regimens were similar: 31% and 25% at 9 h, 53% and 50% at 24 h, 66%
      and 64% at 48 h, the end point for outcome assessment. The median number of
      rFVIIa infusions needed to achieve a successful course was significantly greater
      for the standard-dosage (n = 3) than for the high-dosage regimen (n = 1), and the
      median amount of rFVIIa ultimately used per successful course was identical (270
      microg kg(-1)). CONCLUSION: Our results indicate that a high-dosage regimen with
      rFVIIa for home treatment of hemarthroses is effective, safe, does not imply an
      increased consumption of rFVIIa and requires the infusion of a smaller number of
      rFVIIa doses. Its convenience is particularly relevant in cases with difficult
      venous access and in hemorrhages into target joints.

PMID- 16420568
TI  - Thrombin generation time is a novel parameter for monitoring enoxaparin therapy
      in patients with end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) who receive enoxaparin
      are at increased risk for adverse bleeding episodes. This phenomenon appears to
      occur despite judicious monitoring of antifactor Xa (aFXa) activity. Better
      monitoring parameters are needed to quantify the anticoagulant effects of
      enoxaparin in the ESRD population. OBJECTIVES: The objective of this study was to
      determine the utility of using thrombin generation time (TGT), platelet
      contractile force (PCF) and clot elastic modulus (CEM) to monitor the degree of
      anticoagulation in ESRD subjects, and to compare these results to aFXa activity,
      the current gold-standard monitoring parameter. METHODS: Eight healthy volunteers
      without renal dysfunction and eight ESRD subjects were enrolled into this study.
      Subjects received a single dose of enoxaparin 1 mg kg(-1) subcutaneously, and
      blood samples were obtained for the determination of aFXa activity, TGT, PCF and
      CEM at baseline, 4, 8, and 12 h postdose. RESULTS: Baseline, 4, 8, and 12-h aFXa
      activity concentrations were not different between groups. However, the
      corresponding TGT at 8 and 12 h was significantly prolonged in the ESRD group (P
      = 0.04, and P = 0.008, respectively). The 4-h peak TGT trended toward
      significance (P = 0.06). There were no differences in PCF or CEM across time.
      CONCLUSIONS: These data suggest that the parameter aFXa activity is a poor
      predictor of the anticoagulant effect of enoxaparin in patients with ESRD.
      Thrombin generation time appears to be more sensitive to the antithrombotic
      effects of enoxaparin in this population. Further large-scale trials are needed
      to corroborate these data.

PMID- 16420569
TI  - The measurement of low levels of factor VIII or factor IX in hemophilia A and
      hemophilia B plasma by clot waveform analysis and thrombin generation assay.
AB  - BACKGROUND: Precise assessment of clotting function is essential for monitoring
      of hemostatic treatment for hemophilias A and B. MATERIALS AND METHODS: Clot
      waveform analysis and thrombin generation assays were performed on factor (F)
      VIII- and FIX-deficient plasmas, which had been reconstituted with known amounts
      of recombinant FVIII (rFVIII) and affinity-purified FIX respectively. Clot
      waveforms were assessed qualitatively and quantitatively by measuring the
      parameters clotting time, maximum coagulation velocity (Min1), and maximum
      coagulation acceleration (Min2). The thrombin generation assay was also assessed
      qualitatively and measurements made of time to peak and peak height. RESULTS:
      Overall results obtained with both assays showed good correlation for both
      clotting factors confirming that the changes in clotting waveform reflected
      changes in thrombin generation. Both assays demonstrated a predictable dose
      response to the addition of FVIII or IX. However, clot waveform analysis was more
      sensitive than the thrombin generation assay, particularly in detecting very low
      levels (0-0.1 IU dL(-1)) of both factors. CONCLUSIONS: These data suggest that
      the application of clot waveform analysis to the routine management of the
      hemophiliacs could increase our understanding of the clinical significance of low
      levels of FVIII and FIX that cannot be measured by assays in current use. This
      may be particularly useful in the management of hemophiliacs with inhibitors or
      undergoing gene therapy.

PMID- 16420570
TI  - Protein S multimers and monomers each have direct anticoagulant activity.
AB  - BACKGROUND AND OBJECTIVES: Plasma protein S (PS) is an essential anticoagulant
      that has activated protein C-independent, direct anticoagulant activity (PS
      direct). It was reported that monomeric purified PS has poor PS-direct and that a
      subpopulation of multimeric purified PS has high PS-direct and high affinity for
      phospholipids. We independently examined the relative PS-direct and affinity for
      phospholipids of monomeric and multimeric PS and we obtained contrasting results.
      METHODS AND RESULTS: Unpurified recombinant protein S (rPS) was monomeric and had
      PS-direct potency similar to that of both PS in plasma and multimeric affinity
      purified PS, as measured in plasma assays for PS-direct and in thrombin
      generation assays. Multimers of unpurified rPS were not induced by
      ethylenediaminetetraacetic acid (EDTA), pH 2.5, NaSCN, or barium
      adsorption/elution. Multimers were induced by chromatography in the presence of
      EDTA and thus may be concentration-dependent. In contrast to a different report,
      monomers, dimers, trimers, and higher-order PS forms were clearly separated in
      sedimentation velocity experiments and multimers were not dissociated by adding
      Ca(2+). Active plasma-derived and recombinant immunoaffinity-purified PS were
      fractionated into monomers and multimers. On a mass basis, monomers and multimers
      had similar specific PS-direct and ability to compete with prothrombinase
      components (factors Xa/Va) for limiting phospholipids. FXa ligand blotted to both
      monomers and multimers. CONCLUSIONS: Plasma PS-direct is similar to that of
      affinity-purified PS and unpurified rPS. Under our conditions, monomeric and
      multimeric PS have similar PS-direct and ability to compete for phospholipids.
      Discordant earlier findings are likely due to loss of PS-direct during
      conventional purification procedures.

PMID- 16420571
TI  - Limited generation of activated protein C during infusion of the protein C
      activator thrombin analog W215A/E217A in primates.
AB  - Anticoagulation with activated protein C (APC) reduces the mortality of severe
      sepsis. We investigated whether the circulating protein C (PC) pool could be
      utilized for sustained anticoagulation by endogenous APC. To generate APC without
      procoagulant effects, we administered the anticoagulant thrombin mutant
      W215A;E217A (WE) to baboons. In preliminary studies, administration of high dose
      WE (110 microg kg(-1) i.v. bolus every 120 min; n = 2) depleted PC levels by 50%
      and elicited transient APC bursts and anticoagulation. The response to WE became
      smaller with each successive injection. Low dose WE infusion (5 microg kg(-1)
      loading + 5 microg kg(-1) h(-1) infusion; n = 5) decreased plasma PC activity by
      15%, from 105% to 90%, to a new equilibrium within 60 min. APC levels increased
      from 7.5 ng mL(-1) to 86 ng mL(-1) by 40 min, then declined, but remained
      elevated at 34 ng mL(-1) at 240 min. A 22-fold higher dose WE (n = 5) decreased
      PC levels to 60% by 60 min without significant further depletion in 5 h. The APC
      level was 201 ng mL(-1) at 40 min and decreased to 20 ng mL(-1) within 120 min
      despite continued activator infusion. Co-infusion of WE and equimolar soluble
      thrombomodulin (n = 5) rapidly consumed about 80% of the PC pool with significant
      temporal increase in APC generation. In conclusion, low-grade PC activation by WE
      produced sustained, clinically relevant levels of circulating APC. Limited PC
      consumption in WE excess was consistent with the rapid depletion of cofactor
      activity before depletion of the PC zymogen. Reduced utilization of circulating
      PC might have similar mechanism in some patients.

PMID- 16420572
TI  - Association of increased fibrinogen concentration with impaired activation of
      anticoagulant protein C.
AB  - BACKGROUND: Low levels of activated protein C (APC) are a risk factor for venous
      thrombosis. The mechanisms leading to interindividual differences in APC are not
      totally elucidated. Protein C is activated by the thrombin-thrombomodulin
      complex. As thrombin binds to fibrinogen and thrombomodulin through a common
      region, it is conceivable that fibrinogen influences the activation of protein C.
      This would help to explain the association between high levels of fibrinogen and
      an increased thrombotic risk. METHODS: We analyzed the association between
      circulating APC levels and fibrinogen concentration in 382 healthy subjects.
      Subsequently, we studied the effect of increasing fibrinogen concentrations on
      the APC generation on cultured endothelial cells. RESULTS: An independent inverse
      association between circulating APC levels and fibrinogen was found
      [betacoefficient, -0.16; 95% confidence interval (95% CI) -0.26, -0.06; P =
      0.001]. For each 100 mg dL(-1) increase in fibrinogen, the independent risk of
      having low APC levels (<0.7 ng mL(-1)) was almost three times higher (OR 2.8; 95%
      CI 1.1, 7.2; P = 0.04). Accordingly, a notable association between increasing
      fibrinogen concentrations and the reduction in the thrombin-thrombomodulin
      dependent activation of protein C on endothelial cells was found (r = -0.57; P =
      0.002). CONCLUSIONS: We present evidence of an inverse association between
      circulating APC and fibrinogen levels. According to this finding together with
      the results of our in vitro experiments, we propose that the impairment in the
      generation of APC on endothelial cells constitutes a new prothrombotic mechanism
      of fibrinogen.

PMID- 16420573
TI  - Murine model of ferric chloride-induced vena cava thrombosis: evidence for effect
      of potato carboxypeptidase inhibitor.
AB  - BACKGROUND/OBJECTIVE: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a
      plasma carboxypeptidase that renders a fibrin-containing thrombus less sensitive
      to lysis. In the present study, we describe the development of a murine model of
      vena cava thrombosis and its use to characterize the antithrombotic activity of
      potato carboxypeptidase inhibitor (PCI) of TAFIa (activated TAFI) in mice.
      METHODS/RESULTS: Vena cava thrombosis was induced by various concentrations of
      FeCl(3) in C57BL/6 mice. A relatively mild stimulus (3.5% FeCl(3)) induced
      thrombosis that was consistent and sensitive to reference antithrombotic agents
      such as clopidogrel and heparin. Dose-response studies identified a PCI dose (5
      mg kg(-1) bolus plus 5 mg kg(-1) h(-1), i.v.) that produced a maximum 45%
      decrease in vena cava thrombus mass as assessed by protein content (n = 8, P <
      0.01 compared to vehicle) in the 3.5% FeCl(3)-induced model without exogenous
      tissue plasminogen activator administration. In contrast, PCI had no effect on
      3.5% FeCl(3)-induced carotid artery thrombosis in mice. In a tail transection
      bleeding model, the 5 mg kg(-1) bolus plus 5 mg kg(-1) h(-1) dose of PCI
      increased tail-bleeding time up to 3.5 times control (n = 8, P < 0.05). The ex
      vivo activity of antithrombotic doses of PCI was also demonstrated by the
      enhanced lysis of whole blood clots formed in a thrombelastograph with the
      addition of a sub-threshold concentration of tPA. CONCLUSION: These studies
      provide evidence for a role of TAFIa in venous thrombosis in mice, and describe
      an optimized vena cava injury model appropriate for the evaluation of
      antithrombotic drugs and the characterization of novel therapeutic targets.

PMID- 16420574
TI  - Validation of rotation thrombelastography in a model of systemic activation of
      fibrinolysis and coagulation in humans.
AB  - BACKGROUND: Thrombelastography (TEG) is a whole blood assay to evaluate the
      viscoelastic properties during blood clot formation and clot lysis. Rotation
      thrombelastography (e.g. ROTEM) has overcome some of the limitations of classical
      TEG and is used as a point-of-care device in several clinical settings of
      coagulation disorders. Endotoxemia leads to systemic activation of the
      coagulation system and fibrinolysis in humans. OBJECTIVES: We validated whether
      ROTEM is sensitive to endotoxin induced, tissue factor-triggered coagulation and
      fibrinolysis and if its measures correlate with biohumoral markers of coagulation
      and fibrinolysis. PATIENTS AND METHODS: Twenty healthy male volunteers
      participated in this randomized placebo-controlled trial. Volunteers received
      either 2 ng kg(-1) National Reference Endotoxin or saline. RESULTS: Endotoxemia
      significantly shortened ROTEM clotting time (CT) by 36% (CI 0.26-0.46; P < 0.05)
      with a strong inverse correlation with the peak plasma levels of prothrombin
      fragments (F(1 + 2)) (r = -0.83, P < 0.05). Additionally, endotoxin infusion
      enhanced maximal lysis (ML) 3.9-fold (CI: 2.5-5.2) compared with placebo or
      baseline after 2 h (P < 0.05). Peak ML and peak tissue plasminogen activator (t
      PA) values correlated excellently (r = 0.82, P < 0.05). ROTEM parameters clot
      formation time and maximal clot firmness were not affected by LPS infusion,
      whereas platelet function analyzer (PFA-100) closure times decreased.
      CONCLUSIONS: Rotation thrombelastography (ROTEM) detects systemic changes of in
      vivo coagulation activation, and importantly it is a point of care device, which
      is sensitive to changes in fibrinolysis in humans. The ex vivo measures CT and ML
      correlate very well with established in vivo markers of coagulation activation
      (F(1 + 2)) and fibrinolysis (t-PA), respectively.

PMID- 16420575
TI  - The interaction of von Willebrand factor-A1 domain with collagen: mutation G1324S
      (type 2M von Willebrand disease) impairs the conformational change in A1 domain
      induced by collagen.
AB  - BACKGROUND: It is established that the A3 domain in von Willebrand factor (VWF)
      contains the major collagen-binding site. However, there are conflicting reports
      describing the capacity of the A1 domain to interact with collagen types I and
      III. METHODS: In this study, we have used recombinant VWF-A1 polypeptides, as
      well as conformation-specific monoclonal antibodies (mAb), to analyze the A1
      collagen interaction. RESULTS: The A1 domain bound to collagen with K(d)
      approximately 8.0 nm and this binding was blocked by the mAb 6G1, which blocks
      the interaction between ristocetin and VWF. In addition, collagen-bound A1
      protein was able to support flow-dependent adhesion of platelets, demonstrating
      that the binding sites for collagen and glycoprotein (GP)Ib are different.
      Analysis with two conformation-specific mAb demonstrated that the structure of
      the A1 domain changed as a result of the binding to collagen. In contrast, the
      antibodies failed to detect conformational change in the G1324S mutant (type 2M
      von Willebrand disease). Thus, direct binding to collagen induces a change in the
      structural conformation within the VWF-A1 domain, and the G1324S substitution
      prevents this conformational change. CONCLUSION: This study has shown that the
      isolated A1 domain can simultaneously bind to collagen and platelet GPIb,
      supporting platelet adhesion under high-flow conditions. In addition, this study
      has used mAb to demonstrate that the binding of the isolated A1 domain or full
      length VWF to collagen is accompanied by a conformational change in A1 domain.

PMID- 16420576
TI  - Lentivirus degradation and DC-SIGN expression by human platelets and
      megakaryocytes.
AB  - BACKGROUND AND AIM: As platelets are able to endocytose human immunodeficiency
      virus (HIV), we have investigated the fate of lentiviruses when endocytosed by
      human platelets and megakaryocytes (MK), and have characterized a specific
      receptor directly involved in this function. METHODS: Genetically modified (non
      replicative) lentiviruses with an HIV envelope (HIV-e) or with a vesicular
      stomatitis virus protein G envelope (VSV-e) were alternatively used and their
      interaction with platelets and MK analyzed by electron microscopy (EM) and
      immunoEM. RESULTS: When incubated with platelets, HIV-e and VSV-e lentiviruses
      were internalized in specific endocytic vesicles and trafficked to the surface
      connected canalicular system (SCCS). Double immunolabeling for the viral P24 core
      protein and alpha-granule markers showed that lentiviruses were degraded in the
      SCCS after contact with alpha-granule proteins. In culture MK, lentiviruses were
      found in endocytic vesicles and accumulated in acid phosphatase-containing
      multivesicular bodies (MVB). The expression of the pathogen receptor dendritic
      cell-specific ICAM-grabbing non-integrin (DC-SIGN) was then demonstrated in
      platelets by flow cytometry, immunoEM and Western blot. Anti-DC-SIGN antibodies
      decreased HIV-e lentivirus internalization by platelets, showing that the
      receptor is functional. Specific signals for DC-SIGN protein and mRNA were also
      found in MK. CONCLUSION: This study indicates that platelets and MK can
      internalize lentiviruses in a pathway, which either provide a shelter to
      lentiviral particles or alternatively disrupts viral integrity. The receptor DC
      SIGN is involved in this function.

PMID- 16420577
TI  - Megakaryocytes derived from human embryonic stem cells: a genetically tractable
      system to study megakaryocytopoiesis and integrin function.
AB  - BACKGROUND: The platelet fibrinogen receptor, a heterodimer consisting of
      integrin subunits alpha(IIb) and beta(3), is required for platelet aggregation,
      spreading, and hemostasis. Platelet agonists such as thrombin and adenosine
      diphosphate (ADP) lead to the activation of alpha(IIb)beta(3), thereby enhancing
      its affinity and avidity for binding fibrinogen (inside-out signaling).
      Furthermore, fibrinogen binding to alpha(IIb)beta(3) triggers cytoskeletal
      changes and granule release (outside-in signaling). AIM: Genetic approaches to
      characterize the molecular pathways involved in alpha(IIb)beta(3) signaling are
      not possible with anucleate blood platelets. Therefore, we have established an
      OP9 stromal cell co-culture system to generate megakaryocytes from human
      embryonic stem cells (hESCs). RESULTS: alpha(IIb)beta(3) activation, measured by
      soluble fibrinogen binding to hESC-derived megakaryocytes, /GPIbalpha(+) cells,
      is readily detectable following stimulation with known platelet agonists. Dose
      response curves for peptide agonists specific for the two platelet thrombin
      receptors, protease-activated receptor 1 (PAR1) and PAR4, show a relative
      responsiveness that mirrors that of human platelets, and sub-maximal ADP
      responses are augmented by epinephrine. Moreover, hESC-derived megakaryocytes
      undergo lamellipodia formation, actin filament assembly, and vinculin
      localization at focal adhesions when plated on a fibrinogen-coated surface,
      characteristic of alpha(IIb)beta(3) outside-in signaling. Undifferentiated hESCs
      genetically modified by lentiviral infection can be cloned and maintained in an
      undifferentiated state and then differentiated into megakaryocytes capable of
      alpha(IIb)beta(3) activation. CONCLUSION: Using hESCs, we have developed a
      renewable source of human megakaryocytes, and a genetically tractable system for
      studying megakaryocytopoiesis and alpha(IIb)beta(3) signaling in the native
      cellular environment.

PMID- 16420578
TI  - ERK2 activation in arteriolar and venular murine thrombosis: platelet receptor
      GPIb vs. P2X.
AB  - The functional significance of extracellular signal-regulated kinase 2 (ERK2)
      activation was investigated during shear induced human platelet aggregation
      (SIPA) in vitro and during shear controlled thrombosis in vivo in intestinal
      arterioles and venules of wild type (WT) and transgenic (TG) mice with platelet
      specific overexpression of human P2X(1) (TG). In SIPA, ERK2 was rapidly
      phosphorylated during GPIb stimulation, its activation contributing to SIPA for
      50%, independently of P2X(1) regulation. Thrombotic occlusion of injured
      arterioles occurred considerably faster in TG (4.3 +/- 2.3 min) than in WT (38 +/
      8 min) arterioles, but occlusion times in TG (19 +/- 12) and WT (48 +/- 4.5 min)
      venules differed less. Both the alphabeta-meATP triggered desensitization of
      platelet P2X(1), as well as P2X(1) antagonism by NF279 or NF449 prolonged mean
      occlusion to about 75 min in WT and 65 min in TG arterioles, but venular
      occlusion times were less affected. Preventing ERK2 activation by U0126 prolonged
      occlusion times in TG (41 +/- 10 min) and WT (51 +/- 17) arterioles more than in
      TG (46 +/- 5 min) and WT (56 +/- 6 min) venules, uncovering a role for ERK2 in
      shear controlled thrombosis. Antagonism of GPIb by a recombinant murine von
      Willebrand factor (VWF)-A1 fragment prolonged occlusion times to comparable
      values, ranging from 55 to 58 min, both in TG and WT arterioles and venules.
      Further inhibition strategies, combining VWF-A1, U0126 and NF449 in WT and TG
      mice and resulting in occlusion in various time windows, identified that
      inhibition by VWF-A1 largely abrogated the ERK2 contribution to thrombosis. In
      conclusion, P2X(1) and ERK2 both participate in shear stress controlled
      thrombosis, but ERK2 activation is initiated predominantly via GPIb-VWF
      interactions.

PMID- 16420579
TI  - Nicotine induces tissue factor expression in cultured endothelial and smooth
      muscle cells.
AB  - BACKGROUND AND OBJECTIVES: Cigarette smoking is associated with an increased risk
      to develop myocardial infarction and ischemic stroke. However, the mechanisms
      responsible for these effects are still poorly understood. AIM: To investigate
      whether nicotine, the major component of cigarette smoking, and its main
      metabolite, cotinine, might induce a pro-thrombotic state via stimulation of
      tissue factor (TF) expression in two cell population widely represented in the
      arterial wall such as endothelial cells (ECs), and smooth muscle cells (SMCs).
      METHODS AND RESULTS: Incubation of ECs and SMCs with nicotine and cotinine
      induced TF expression in both cell types in a dose-dependent fashion, exerting
      its effect at the transcriptional level, as demonstrated by semiquantitative and
      by real-time PCR. Nicotine- and cotinine-induced TF expression was mediated by
      the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB),
      as demonstrated by electrophoretic mobility shift assay and by the suppression of
      TF expression by the NF-kappaB inhibitor, pyrrolidine dithio carbamate ammonium.
      CONCLUSIONS: These data indicate that nicotine and cotinine exert direct effects
      on ECs and SMCs, shifting them toward a pro-thrombotic state via induction of TF
      expression. These effects on cells of the vessel wall might explain, at least in
      part, the deleterious cardiovascular consequences of cigarette smoking.

PMID- 16420581
TI  - Anti-HCV agent, ribavirin, elevates the activity of clotting factor VII in
      patients with hemophilia: a possible mechanism of decreased events of bleeding in
      patients with hemophilia by ribavirin.

PMID- 16420580
TI  - Function-blocking antithrombospondin-1 monoclonal antibodies.
AB  - BACKGROUND: Thrombospondin-1 (TSP-1) has been implicated in many different
      processes based in part on inhibitory activities of anti-TSP-1 monoclonal
      antibodies (mAbs). OBJECTIVE: To map epitopes of 13 anti-TSP-1 mAbs to individual
      modules or groups of modules spanning TSP-1 and the closely related TSP-2
      homolog. RESULTS: The mapping has led to assignment or reassignment of the
      epitopes of four mAbs, refinement of the epitopes of six mAbs, and confirmation
      of the epitopes of the remaining three mAbs. ESTs10, P12, and MA-II map to the N
      terminal domain; 5G11, TSP127.6, and ESTs12 to the third properdin module; C6.7,
      HB8432, and P10 to epidermal growth factor (EGF)-like modules 1 and/or 2; and
      A6.1, mAb133, MA-I, and D4.6 to the calcium-binding wire module. A6.1, which
      recognizes a region of the wire that is identical in mouse and human TSP-1,
      reacts with TSP-1 from both species, and also reacts weakly with human TSP-2. Two
      other mouse antihuman TSP-1 mAbs, A4.1 and D4.6, also react with mouse TSP-1.
      CONCLUSIONS: Consideration of previous literature and mapping of epitopes of
      inhibitory mAbs suggest that biological activities are present throughout TSP-1,
      including the EGF-like modules that have not been implicated in the past. Because
      the epitopes for 10 of the antibodies likely are within 18 nm of one another in
      calcium-replete TSP-1, some of the inhibitory effects may result from steric
      hindrance. Such seems to be the case for mAb133, which binds the calcium-binding
      wire but is still able to interfere with the activation of latent TGF-beta by the
      properdin modules.

PMID- 16420582
TI  - An intronic mutation within FGB (IVS1+2076 a-->g) is associated with
      afibrinogenemia and recurrent transient ischemic attacks.

PMID- 16420583
TI  - Population variation in VKORC1 haplotype structure.

PMID- 16420584
TI  - Haplotypes of the fibrinogen gamma gene do not affect the risk of myocardial
      infarction.

PMID- 16420585
TI  - Statins modulate expression of components of the plasminogen activator/plasmin
      system in human cardiac myocytes in vitro.

PMID- 16420586
TI  - A new method for assessment of an anti-5HT(2A) agent, sarpogrelate hydrochloride,
      on platelet aggregation.

PMID- 16420587
TI  - Factor V deficiency caused by a novel missense mutation, Ile417Thr, in the A2
      domain.

PMID- 16420588
TI  - Screening for bleeding disorders in women with menorrhagia using a platelet
      function analyzer.

PMID- 16420589
TI  - More on aspirin resistance: position paper of the Working Group on Aspirin
      Resistance. Proposal for a Laboratory Test Guiding Algorithm.

PMID- 16420590
TI  - About the role of TLR2 and TLR4 in cytokine secretion by murine macrophages in
      response to Candida albicans.

PMID- 16420591
TI  - Emergence of Salmonella Blockley, possible association with long-term reactive
      arthritis, and antimicrobial resistance.
AB  - We previously reported the case of a patient who became ill with Salmonella
      serotype Blockley after eating a chicken meal and who was still suffering
      symptoms of salmonella-reactive arthritis 10 years after the initial infection.
      The immunological consequences of infection were of concern and prompted a
      literature review because of the possibility that Salmonella Blockley may be more
      likely to cause long-term illness in certain patients than more common serovars.
      The review revealed the additional cause for concern of plasmid-borne extended
      spectrum beta-lactamases and the high frequency of integron-associated multidrug
      resistance in some isolates. The serovar was described in 1955 in the USA and
      Europe. It has become common in South East Asia and recently has been reported
      more often in Europe. A review of reactive arthritis outbreaks shows that
      information on the incidence and duration of the condition caused by serovars
      other than Salmonella serotype Enteritidis and Salmonella serotype Typhimurium is
      very limited. Rheumatologists can assist microbiologists and epidemiologists by
      reporting relevant cases of long-term reactive arthritis.

PMID- 16420592
TI  - SCCmec in staphylococci: genes on the move.
AB  - Staphylococcal cassette chromosome (SCC) elements are, so far, the only vectors
      described for the mecA gene encoding methicillin resistance in staphylococci.
      SCCmec elements are classified according to the type of recombinase they carry
      and their general genetic composition. SCCmec types I-V have been described, and
      SCC elements lacking mecA have also been reported. In this review, we summarize
      the current knowledge about SCC structure and distribution, including genetic
      variants and rudiments of the elements. Its origin is still unknown, but one
      assumes that staphylococcal cassette chromosome is transferred between
      staphylococci, and mecA-positive coagulase-negative staphylococci may be a
      potential reservoir for these elements. Staphylococcal genomes seem to change
      continuously as genetic elements move in and out, but no mechanism of transfer
      has been found responsible for moving SCC elements between different
      staphylococcal species. Observations suggesting de novo production of methicillin
      resistant staphylococci and horizontal gene transfer of SCCmec will be discussed.

PMID- 16420593
TI  - The major chromoblastomycosis fungal pathogen, Fonsecaea pedrosoi,
      extracellularly releases proteolytic enzymes whose expression is modulated by
      culture medium composition: implications on the fungal development and cleavage
      of key's host structures.
AB  - We investigated the possible secretion of peptidases by F. pedrosoi, when
      conidial cells were cultured in two distinct media. Aspartyl proteolytic activity
      was detected on the Czapeck-Dox-derived supernatant, which was blocked by
      pepstatin, and only active in extremely acidic conditions. The supernatant
      obtained after conidia growth in Kauffman medium presented metallopeptidase
      activity, which was active over a broad pH range and sensitive to 1,10
      phenanthroline and EGTA. Additionally, both culture supernatants were able to
      cleave a wide range of proteinaceous substrates, including important human serum
      proteins (e.g. albumin and immunoglobulin G) and extracellular matrix components
      (e.g. fibronectin and laminin). As peptidases participate in different cellular
      metabolic pathways, we also tested the influence of proteolytic inhibitors on the
      F. pedrosoi conidia development in vitro. The metallopeptidase inhibitors, 1,10
      phenanthroline, EGTA and EDTA, strongly abrogated the growth of conidial forms by
      approximately 95%, 85% and 60%, respectively. Moreover, 1,10-phenanthroline
      blocked the differentiation process from conidia to mycelia, an essential step
      during the F. pedrosoi life cycle. Phenylmethanesulfonyl fluoride, a serine
      peptidase inhibitor, slightly reduced the conidial growth, whereas proteolytic
      inhibitors of cysteine (E-64) and aspartic (pepstatin) type peptidases did not
      alter conidial developmental behavior. In summary, our results showed for the
      first time the expression of extracellular proteolytic activity by F. pedrosoi
      conidial cells.

PMID- 16420594
TI  - Interleukin-18 expression by alveolar epithelial cells type II in tuberculosis
      and sarcoidosis.
AB  - The aims of the present study were to characterize the localization of
      interleukin-18 (IL-18) expression in lung tissue specimens from patients with
      pulmonary tuberculosis, sarcoidosis and controls, and to determine whether human
      alveolar epithelial cells type II (AEC-II) are able to generate IL-18 in primary
      culture. IL-18 was determined using semiquantitative reverse-transcription-PCR
      and localized in lungs using in situ hybridization. IL-18 protein levels were
      determined using the enzyme-linked immunosorbent assay and western blot analysis.
      Alveolar epithelial cells type II (AEC-II) were stimulated in vitro by
      proinflammatory cytokines, lipopolysaccharides, and whole cell lysate from
      Mycobacterium tuberculosis. IL-18 mRNA expression was significantly increased in
      the lungs affected by tuberculosis and sarcoidosis. In situ hybridization
      revealed different sites of expression in tuberculosis and sarcoidosis lungs,
      with AEC-II as one major source of IL-18 in the alveolar compartment. Basal IL-18
      expression could be detected in normal AEC-II. Whole cell lysate from M.
      tuberculosis, but not lipopolysaccharide, led to a strong increase of IL-18 mRNA
      accumulation in AEC-II. Resting AEC-II secreted only small amounts of IL-18, but
      intracellular IL-18 protein levels increased in a time-dependent manner during
      culture. Proinflammatory cytokines tumour necrosis factor-alpha, IL-1beta, and
      interferon-gamma altered IL-18 mRNA expression and mature protein secretion of
      human AEC-II. These findings indicate a possible role for AEC-II and AEC-II
      derived IL-18 in pathomechanisms of granulomatous lung diseases.

PMID- 16420596
TI  - Automatized PCR evaluation of Mycobacterium tuberculosis complex in respiratory
      and nonrespiratory specimens.
AB  - In this study, Mycobacterium tuberculosis complex isolates recovered from
      respiratory and nonrespiratory specimens with culture were evaluated using an
      automatized PCR method. Specimens with suspected tuberculous disease were
      decontaminated and concentrated using the standard N-acetyl-L-cysteine NaOH
      method and were inoculated onto glycerol-supplemented Lowenstein-Jensen media and
      BACTEC B12 vials. Forty-one specimens with typical colonies on solid media and
      127 specimens identified as M. tuberculosis complex in a BACTEC system were
      selected as the study group. As the control group, 46 specimens without growth on
      either culture media were selected. The PCR results were positive in 33 (80.5%)
      and 87 (68.5%) samples that were culture-positive on solid and liquid media,
      respectively. All (100%) culture-negative specimens within the control group were
      also negative in the COBAS AMPLICOR Mycobacterium tuberculosis (MTB) PCR method.
      In conclusion, although it is a fast method for identifying M. tuberculosis
      complex isolates from clinical specimens, the COBAS AMPLICOR MTB PCR method is
      found to be less sensitive than culture techniques, we propose therefore that it
      should only be used in combination with culture results in the clinical diagnosis
      of tuberculosis.

PMID- 16420595
TI  - Bordetella pertussis attachment to respiratory epithelial cells can be impaired
      by fimbriae-specific antibodies.
AB  - Bordetella pertussis attachment to host cells is a crucial step in colonization.
      In this study, we investigated the specificity of antibodies, induced either by
      vaccination or infection, capable of reducing bacterial adherence to respiratory
      epithelial cells. Both sera and purified anti-B. pertussis IgG or IgA fractions
      efficiently reduced attachment. This effect was found to be mediated mainly by
      fimbriae-specific antibodies. Antibodies with other specificities did not
      significantly interfere in the interaction of B. pertussis with respiratory
      epithelial cells, with the exception of antifilamentous hemaglutinin antibodies,
      which reduced bacterial attachment. However, this effect was smaller in magnitude
      than that observed in the presence of fimbriae-specific antibodies. The strong
      agglutinating activity of antifimbriae antibodies seems to be involved in this
      phenomenon.

PMID- 16420598
TI  - Prophylactic use of liposomized tuftsin enhances the susceptibility of Candida
      albicans to fluconazole in leukopenic mice.
AB  - In the present study, we investigated the immunopotentiating activity of the
      immunomodulator tuftsin for the treatment of dose-dependent susceptible Candida
      albicans infection in a murine model. Our results demonstrated that tuftsin
      increases the susceptibility of C. albicans to phagocytosis by activating murine
      macrophages. Fluconazole used for the treatment of mice infected with C. albicans
      showed less in vivo efficacy and proved to be ineffective in the elimination of
      the infection from leukopenic mice even at higher doses. However, the antifungal
      activity of fluconazole against the same isolate of C. albicans significantly
      increased in tuftsin-pretreated mice and resulted in an improved survival rate in
      mice. The treated mice also showed less severity of infection as supported by a
      reduced fungal burden in their kidneys. This study indicates that the use of
      immunopotentiating substances can enhance the therapeutic efficacy of azole
      antifungal agents and thus can effectively combat azole-resistant fungal
      pathogens under conditions of immunosuppression.

PMID- 16420597
TI  - Genotypic drug resistance interpretation algorithms display high levels of
      discordance when applied to non-B strains from HIV-1 naive and treated patients.
AB  - Genotypic drug resistance interpretation algorithms have been developed on
      patients infected with HIV-1 subtype B to interpret complex patterns of
      mutations. As non-B strains are characterised by the natural presence of several
      resistance-related mutations, we examined to what extent this might result in
      interalgorithm discordances in naive and treated patients. We compared the
      prediction by three algorithms (ANRS, Stanford and Rega) of drug susceptibilities
      to diverse HIV-1 strains from 272 naive and 156 treated patients. In naive
      patients, higher levels of interalgorithm discordance were observed for
      predictions of protease inhibitor (0.60-39%) than for predictions of reverse
      transcriptase inhibitor susceptibility (0-4%). The main reason for discordant
      protease inhibitor interpretation was the presence of resistance mutations that
      were natural protease polymorphisms. In contrast, in the treated patients, more
      interalgorithm discordances were observed for predictions of reverse
      transcriptase inhibitor (5-48%) than protease inhibitor susceptibilities (10
      31%). Discordances were related to disagreement between the intermediate and
      susceptible scores, the intermediate and resistant scores and the interpretations
      of complex mutation patterns, related to cross-resistance and antagonistic
      interactions.

PMID- 16420599
TI  - Fate and effect of ingested Bacillus cereus spores and vegetative cells in the
      intestinal tract of human-flora-associated rats.
AB  - The fate and effect of Bacillus cereus F4433/73R in the intestine of human-flora
      associated rats was studied using bacteriological culturing techniques and PCR
      denaturing gradient gel electrophoresis in combination with cell assays and
      immunoassays for detection of enterotoxins. In faecal samples from animals
      receiving vegetative cells, only few B. cereus cells were detected. Spores
      survived the gastric barrier well, and were in some cases detected up to 2 weeks
      after ingestion. Selective growing revealed no major changes in the intestinal
      flora during passage of B. cereus. However, denaturing gradient gel
      electrophoresis analysis with universal 16S rRNA gene primers revealed
      significant changes in the intestinal microbiota of animals dosed with spores.
      Vero cell assays and a commercial kit (BCET-RPLA) did not reveal any enterotoxin
      production from B. cereus F4433/73R in the intestinal tract.

PMID- 16420600
TI  - The synthetic analogue of mycoplasmal lipoprotein FSL-1 induces dendritic cell
      maturation through Toll-like receptor 2.
AB  - Granulocyte-macrophage colony-stimulating factor-differentiated bone marrow
      derived dendritic cells were stimulated with the synthetic lipopeptide S-(2,3
      bispalmitoyloxypropyl)-CGDPKHSPKSF (FSL-1) or the Escherichia coli
      lipopolysaccharide. FSL-1 induced the production of TNF-alpha and IL-12 by
      C57BL/6-derived bone marrow-derived dendritic cells but not by bone marrow
      derived dendritic cells from Toll-like receptor 2-deficient (TLR2(-/-)) mice.
      Lipopolysaccharide induced the production of TNF-alpha and IL-12 by bone marrow
      derived dendritic cells derived from either type of mice. FSL-1 did not induce
      production of IL-10 by bone marrow-derived dendritic cells from either type of
      mice, whereas lipopolysaccharide induced small amounts of IL-10 by bone marrow
      derived dendritic cells from both types of mice. The upregulation by FSL-1 of the
      expression of CD80, CD86 and the MHC class II molecule IA(b) was dose- and time
      dependent on the surfaces of C57BL/6-derived bone marrow-derived dendritic cells
      but not on the surface of TLR2(-/-)-derived bone marrow-derived dendritic cells.
      Lipopolysaccharide upregulated the expression of these molecules on the surfaces
      of bone marrow-derived dendritic cells from both types of mice. The expression of
      CD11c on the surfaces of C57BL/6-derived bone marrow-derived dendritic cells was
      upregulated by stimulation with both FSL-1 and lipopolysaccharide up to 12 h;
      thereafter, the expression was downregulated. The results suggest that FSL-1 can
      accelerate maturation of bone marrow-derived dendritic cells and this FSL-1
      activity is mediated by TLR2.

PMID- 16420601
TI  - Structures of the core oligosaccharide and O-units in the R- and SR-type
      lipopolysaccharides of reference strains of Pseudomonas aeruginosa O-serogroups.
AB  - Highly phosphorylated core oligosaccharides and those substituted with one O
      antigen repeating unit were obtained by mild acid degradation or strong alkaline
      hydrolysis of lipopolysaccharide samples from 23 reference strains representing
      all Pseudomonas aeruginosa O-serogroups. Studies by high-resolution electrospray
      ionization mass spectrometry and two-dimensional NMR spectroscopy revealed both
      conserved and variable structural features of the lipopolysaccharides of various
      O-serogroups. The upstream terminal saccharide of the O-antigen, which
      contributes most to the immunospecificity of the bacteria, was defined in 11 from
      a total of 13 O-serogroups. The data obtained link together the known
      biosynthesis pathways, genetics and serology of the P. aeruginosa
      lipopolysaccharide.

PMID- 16420602
TI  - The effect of DNA priming-protein boosting on enhancing humoral immunity and
      protecting mice against lethal HSV infections.
AB  - Herpes simplex virus produces primary and latent infections with periodic
      recurrency. The prime-boost immunization strategies were studied using a DNA
      vaccine carrying the full-length glycoprotein D-1 gene and a baculovirus-derived
      recombinant glycoprotein D, both expressing herpes simplex virus glycoprotein D-1
      protein. Immunization with recombinant DNAs encoding antigenic proteins could
      induce cellular and humoral responses by providing antigen expression in vivo.
      Higher immune response, however, occurred when the recombinant proteins followed
      DNA inoculation. While all groups of the immunized mice and positive control
      group could resist virus challenge, a higher virus neutralizing antibody level
      was detected in the animals receiving recombinant protein following DNA
      vaccination.

PMID- 16420603
TI  - Inhibition of microbial adhesion to silicone rubber treated with biosurfactant
      from Streptococcus thermophilus A.
AB  - Microbial adhesion of four bacterial and two yeast strains isolated from
      explanted voice prostheses to silicone rubber before and after conditioning with
      a biosurfactant obtained from the probiotic bacterium Streptococcus thermophilus
      A was investigated in a parallel plate flow chamber. The silicone rubber with and
      without an adsorbed biosurfactant layer was characterized using contact angle
      measurements. Water contact angles indicated that the silicone rubber surface
      with adsorbed biosurfactant was more hydrophilic (58 degrees) than bare silicone
      rubber (109 degrees). The results obtained showed that the biosurfactant was
      effective in decreasing the initial deposition rates, and the number of bacterial
      cells adhering after 4 h, for all microorganisms tested. A decrease in the
      initial deposition rate was observed for Rothia dentocariosa GBJ 52/2B and
      Staphylococcus aureus GB 2/1 from 1937+/-194 to 179+/-21 microorganisms cm(-2) s(
      1) and from 1255+/-54 to 233+/-26 microorganisms cm(-2) s(-1), respectively,
      accounting for an 86% reduction of the initial deposition rate for both strains.
      The number of bacterial cells adhering to the silicone rubber with preadsorbed
      biosurfactant after 4 h was further reduced by 89% and 97% by the two strains,
      respectively. The two yeast strains tested showed less reduction in adhesion
      after 4 h, to values between 67% and 70%. Such a pretreatment with surface-active
      compounds may constitute a promising strategy to reduce the microbial
      colonization rate of silicone rubber voice prostheses.

PMID- 16420604
TI  - Comparison by flow cytometry of immune changes induced in human monocyte-derived
      dendritic cells upon infection with dengue 2 live-attenuated vaccine or 16681
      parental strain.
AB  - Dengue is an important threat for world-wide public health. Different vaccines
      are under development, which are currently assessed using a battery of in vitro
      and in vivo assays before moving on to humans. It is also important to assess
      vaccine characteristics on human primary cells; among them, dendritic cells, the
      most efficient antigen-presenting cells, are the first targets of dengue virus
      infection. In this study, we used flow cytometry to compare the consequences of
      such an infection by dengue serotype 2 live-attenuated vaccine (LAV2) or its
      parental strain DEN2 16681 (DEN2). Optimal conditions of infection have first
      been defined by a mathematical approach, and flow cytometry allowed studying
      modifications induced in both infected and noninfected dendritic cell populations
      after surface and intracellular labeling. Both DEN2 and LAV2 increased the
      expression of the phenotypic markers CD80, CD86, CD40, CD1a, HLA ABC and CD83,
      demonstrating cellular activation. Stimulated dendritic cells produced tumor
      necrosis factor-alpha in particular, and, to a lower extent, interleukin 6. Of
      importance, whereas DEN2 induced cytokine production both in the infected and
      noninfected populations, LAV2-induced cytokine production was restricted to the
      infected population. This limited activation triggered by LAV2 would be in
      agreement with its attenuation. In conclusion, these in vitro experiments using
      primary human dendritic cells may participate, in combination with other assays,
      to the evaluation of the immunogenicity and safety of dengue vaccine candidates.

PMID- 16420605
TI  - The phototoxicity of phenothiazinium-based photosensitizers to bacterial
      membranes.
AB  - The ability of phenothiazinium-based photosensitizers to induce photodamage to
      Escherichia coli membranes is investigated. Phenothiazinium-based
      photosensitizers were found to be somewhat lipophilic (log P>0.7) and to induce
      surface-pressure changes (3-12 mN m(-1)) in lipid monolayers mimetic of bacterial
      membranes, implying that these molecules are able to penetrate biological
      membranes. Under dark and light conditions (3.15 J cm(-1) for 30 min),
      phenothiazinium-based photosensitizers were incubated with E. coli cells. These
      cells showed levels of dark bacteriolysis that ranged between 6% and 13%, with
      light conditions leading to no significant increase in these levels. Gas
      chromatography-based analyses showed such incubations to produce no significant
      changes in the levels of C(16) and C(18) fatty acid chain saturation found in E.
      coli whole lipid-extracts. It is concluded that the phenothiazinium-based
      photosensitizers studied may not use E. coli membranes as their primary
      photodynamic target, but may inflict photodamage on cytoplasmic targets, possibly
      DNA.

PMID- 16420606
TI  - Food-protein enzymatic hydrolysates possess both antimicrobial and
      immunostimulatory activities: a "cause and effect" theory of bifunctionality.
AB  - The antimicrobial activity (the ability to activate the microbial autolytic
      system) and immunostimulatory activity (the ability to improve the phagocytic
      cell functioning) of 20 food-protein hydrolysates [five food proteins (casein,
      alpha-lactalbumin, beta-lactoglobulin, ovalbumin and serum albumin) hydrolyzed
      with four gastrointestinal proteinases (trypsin, alpha-chymotrypsin, pepsin and
      pancreatin)] were examined. All the food-protein hydrolysates acted
      antimicrobially in vitro towards all 24 microbial strains tested: autolysis of 20
      naturally autolyzing strains was activated, with the autolysis activation index
      (K(A)) ranging from 1.04 to 22.0, while autolysis was induced to values of 2.81
      56.7% in four naturally nonautolyzing strains. When given to mice per os, all the
      food-protein hydrolysates enhanced the phagocytosing capacity of peritoneal
      macrophages, with the enhancement index (K(I)) ranging from 1.02 to 1.41. A
      direct correlation between K(A) and K(I) was observed. We make the presumption
      that K(I) is a function of K(A).

PMID- 16420607
TI  - Human serum and mucosal antibody responses to outer membrane protein G1b of
      Moraxella catarrhalis in chronic obstructive pulmonary disease.
AB  - Moraxella catarrhalis is an important human pathogen that causes otitis media,
      sinusitis, and lower respiratory tract infections in adults with chronic
      obstructive pulmonary disease. Outer membrane protein G1b is a approximately 29
      kDa protein that has a high degree of homology among strains, contains surface
      exposed epitopes, and is a potential vaccine candidate. The ompG1b gene was
      cloned, expressed in Escherichia coli, and purified. To assess the expression of
      outer membrane protein G1b during human infection, paired serum and sputum
      supernatants from patients with chronic obstructive pulmonary disease followed
      prospectively were studied by enzyme-linked immunosorbent assays with recombinant
      outer membrane protein G1b to detect antibodies made specifically during carriage
      of M. catarrhalis. Overall, 39% of patients developed either a serum IgG (28.6%)
      or a sputum supernatant IgA (19.2%) response to outer membrane protein G1b
      following 100 episodes of acquisition and clearance of M. catarrhalis. A sputum
      supernatant IgA response was more likely following exacerbations compared with
      asymptomatic colonizations, whereas a serum IgG response occurred at similar
      rates. Serum IgG antibodies following natural infection were directed toward
      surface-exposed epitopes of outer membrane protein G1b. Overall, these studies
      show that outer membrane protein G1b is expressed during infection of the human
      respiratory tract and that human antibodies bind to outer membrane protein G1b
      epitopes on the bacterial surface. These observations indicate that outer
      membrane protein G1b should be evaluated further as a vaccine antigen.

PMID- 16420610
TI  - Bacterial motility: links to the environment and a driving force for microbial
      physics.
AB  - Bacterial motility was recognized 300 years ago. Throughout this history,
      research into motility has led to advances in microbiology and physics. Thirty
      years ago, this union helped to make run and tumble chemotaxis the paradigm for
      bacterial movement. This review highlights how this paradigm has expanded and
      changed, and emphasizes the following points. The absolute magnitude of swimming
      speed is ecologically important because it helps determine vulnerability to
      Brownian motion, sensitivity to gradients, the type of receptors used and the
      cost of moving, with some bacteria moving at 1 mm s(-1). High costs for high
      speeds are offset by the benefit of resource translocation across submillimetre
      redox and other environmental gradients. Much of environmental chemotaxis appears
      adapted to respond to gradients of micrometres, rather than migrations of
      centimetres. In such gradients, control of ion pumps is particularly important.
      Motility, at least in the ocean, is highly intermittent and the speed is variable
      within a run. Subtleties in flagellar physics provide a variety of reorientation
      mechanisms. Finally, while careful physical analysis has contributed to our
      current understanding of bacterial movement, tactic bacteria are increasingly
      widely used as experimental and theoretical model systems in physics.

PMID- 16420611
TI  - Evolutionary algorithms and flow cytometry to examine the parameters influencing
      transconjugant formation.
AB  - An evolutionary algorithm was used to determine the optimal combination of
      parameters for transconjugant formation. As a model system, a gfp tagged TOL
      plasmid pWW0 was chosen to examine transfer from Pseudomonas putida to
      Escherichia coli. A comparison of flow cytometry results with plating and
      microscopy showed that the majority of transconjugants were not culturable. The
      transconjugant ratio therefore was determined by flow cytometry. The evolutionary
      algorithm showed that the optimal conditions were obtained at 28 degrees C and at
      the highest nutrient concentrations. This work demonstrates that evolutionary
      algorithms can be used to find optimal parameter interactions in environmental
      microbiology.

PMID- 16420612
TI  - Characterization of human intestinal bifidobacteria using competitive PCR and PCR
      TTGE.
AB  - In this study, a competitive PCR was developed to estimate the quantity of
      bifidobacteria in human faecal samples using two 16S rRNA gene Bifidobacterium
      genus-specific primers, Bif164f and Bif662r. A PCR-temporal temperature gradient
      gel electrophoresis (TTGE) with the same primers also allowed us to describe the
      Bifidobacterium species present in these faecal samples. The PCR product obtained
      from the competitor had 467 bp, and was 47 bp shorter than the PCR products
      obtained from Bifidobacterium strains. The number of bifidobacterial cells was
      linear from 10 to 10(8) cells per PCR assay. Taking into account the dilutions of
      the extracted DNA, the linear range was over 8 x 10(5) bifidobacteria g(-1) of
      faeces. Reproducibility was assessed from 10 independent DNA extractions from the
      same stool and the coefficient of variation was 0.5%. When the competitive PCR
      was compared with the culture method, a similar count of seven out of nine
      Bifidobacterium pure cultures were obtained, or had a difference inferior or
      equal to 1 log(10). In faecal samples, the enumeration of Bifidobacterium genus
      in most cases gave higher results with competitive PCR than with culture on
      selective Columbia-Beerens agar pH 5 (P < 0.05). In conclusion, this competitive
      PCR allows a rapid, highly specific and reproducible quantification of
      Bifidobacterium genus in faecal samples. TTGE fragments co-migrating with B.
      longum CIP64.63 fragment were found in 10 out of 11 faecal samples.
      Bifidobacterium adolescentis and B. bifidum were detected in five out of 11
      subjects. Thus, cPCR and PCR-TTGE can be associated in order to characterize
      human faecal bifidobacteria.

PMID- 16420613
TI  - Molecular bacterial diversity of a forest soil under residue management regimes
      in subtropical Australia.
AB  - A major operational change in exotic pine plantations of subtropical Australia
      has been the decision to retain postharvest residues on site. A long-term field
      experiment was established in February 1996 to examine the impacts of residue
      management regimes [i.e. the postharvest residues removed (G0R), natural amount
      of residues retained (G1R) and residue quantity doubled and retained (G2R)] on
      tree growth (F1 hybrid pine) and sustainable soil management. Twelve soil
      samples, which included the above three residue regimes with four replicates,
      were collected at plantation age 6.4 years. A 16S rRNA gene clone library was
      established following soil community DNA extraction, polymerase chain reaction
      amplification and cloning. A total of 324 clones, including 27 from each sample,
      were randomly selected and sequenced to represent the bacterial composition and
      diversity of the clone library and thus the soil bacterial community under the
      residue management regimes. Phylogenetic analyses indicated that Acidobacteria
      (37.6%) and Proteobacteria (35.6%) were the dominant components of the soil
      bacterial community, followed by Actinobacteria (14.7%),
      Chlamydiae/Verrucomicrobia (7.3%), Unclassified Bacteria (3.8%) and
      Gemmatimonadetes (1.0%). Analysis of molecular variance revealed that there was
      no significant difference in bacterial composition and diversity among the
      residue management regimes or their replicated samples.

PMID- 16420615
TI  - Wood-inhabiting fungal communities in woody debris of Norway spruce (Picea abies
      (L.) Karst.), as reflected by sporocarps, mycelial isolations and T-RFLP
      identification.
AB  - Wood-inhabiting fungi play a key role in forest ecosystems and constitute an
      essential part of forest biodiversity. We therefore examined the composition and
      abundance of wood-inhabiting fungi by three methods: sporocarp counts, mycelial
      culturing and direct amplification of internal transcribed spacer terminal
      restriction fragment length polymorphism from wood combined with sequencing of
      reference rDNA. Seven-year-old slash piles left after a thinning were analyzed in
      a 50-year-old Norway spruce plantation. Fifty-eight fungal species were detected
      from the piled branches and treetops. More species were revealed by sporocarp
      counts and cultured mycelia than by direct amplification from wood. In principle,
      sporocarp monitoring may reveal all fruiting taxa, but it poorly reflects their
      relative abundance in the wood. In contrast, terminal restriction fragment length
      polymorphism will record the most frequent fungal taxa in the wood, but it may
      overlook uncommon taxa. Culturing mycelia from wood gives a bias towards species
      favoured by the cultural medium. The results demonstrate the advantage and the
      limitations of these methods to be considered in analyses of fungal communities
      in wood.

PMID- 16420616
TI  - Microbial communities in wetlands of the Athabasca oil sands: genetic and
      metabolic characterization.
AB  - Naphthenic acids are a complex family of naturally occurring cyclic and acyclic
      carboxylic acids that are present in the acidic fraction of petroleum. Naphthenic
      acids are acutely toxic to aquatic organisms. Previous studies showed that
      wetland sediments exposed to oil sands process water containing naphthenic acids
      had higher rates of naphthenic acid degradation in vitro compared with unexposed
      wetlands. In this study we compare the microbial community structures in
      sediments from wetlands exposed to different amounts of oil sands process water
      using BIOLOG, phospholipid fatty acid analysis and denaturing gradient gel
      electrophoresis of total bacterial DNA. Community profiles were compared using
      cluster analysis. BIOLOG profiles were primarily influenced by seasonal trends
      rather than naphthenic acids content. In contrast, phospholipid fatty acid
      analysis comparisons clustered communities that had higher levels of residual
      oil, although this association was not strong. In contrast, cluster diagrams
      produced from the denaturing gradient gel electrophoresis data clearly separated
      bacterial communities according to naphthenic acids concentrations, indicating
      that naphthenic acids content was a major influence on the composition of the
      bacterial community. In addition, denaturing gradient gel electrophoresis
      profiles indicated that naphthenic acids-exposed bacterial communities were
      homogeneous on a scale of meters, whereas unexposed (off-site) wetlands were less
      homogeneous.

PMID- 16420617
TI  - Succession of bacterial community composition over two consecutive years in two
      aquatic systems: a natural lake and a lake-reservoir.
AB  - The succession in bacterial community composition was studied over two years in
      the epilimnion and hypolimnion of two freshwater systems: a natural lake (Pavin
      Lake) and a lake-reservoir (Sep Reservoir). The bacterial community composition
      was determined by cloning-sequencing of 16S rRNA and by terminal restriction
      fragment length polymorphism. Despite large hydrogeological differences, in the
      Sep Reservoir and Pavin Lake the dominant bacteria were from the same taxonomic
      divisions, particularly Actinobacteria and Betaproteobacteria. In both
      ecosystems, these major bacterial divisions showed temporal fluctuations that
      were much less marked than those occurring at a finer phylogenetic scale.
      Nutrient availability and mortality factors, the nature of which differed from
      one lake to another, covaried with the temporal variations in the bacterial
      community composition at all sampling depths, whereas factors related to seasonal
      forces (temperature and outflow for Sep Reservoir) seemed to account only for the
      variation of the hypolimnion bacterial community composition. No seasonal
      reproducibility in temporal evolution of bacterial community from one year to the
      next was observed.

PMID- 16420618
TI  - Dependent population dynamics between chironomids (nonbiting midges) and Vibrio
      cholerae.
AB  - Vibrio cholerae, the causative agent of cholera, is a natural inhabitant of the
      aquatic ecosystem. Chironomid (nonbiting midges) egg masses were recently found
      to harbour V. cholerae non-O1 and non-O139, providing a natural reservoir for the
      cholera bacterium. Chironomid populations and the presence of V. cholerae in
      chironomid egg masses were monitored. All V. cholerae isolates were able to
      degrade chironomid egg masses. The following virulence associated genes were
      detected in the bacterial isolates: hapA (100%), toxR (100%), hlyA (72%) and ompU
      (28%). The chironomid populations and the V. cholerae in their egg masses
      followed the phenological succession and interaction of host-pathogen population
      dynamics. A peak in the chironomid population was followed by a peak in the V.
      cholerae population. If such a connection is further substantiated for the
      pathogenic serogroups of V. cholerae in endemic areas of the disease, it may lead
      to a better understanding of the role of chironomids as a host for the cholera
      bacterium.

PMID- 16420619
TI  - Antiamoebins, myrocin B and the basis of antifungal antibiosis in the
      coprophilous fungus Stilbella erythrocephala (syn. S. fimetaria).
AB  - Antiamoebins I, III and XVI as well as several others in minor amounts were
      produced by four strains of the coprophilous fungus Stilbella erythrocephala
      (syn. S. fimetaria) in its natural substrate and in liquid culture. The total
      antiamoebin concentration in dung was 126-624 microg g(-1) fresh weight, with
      minimum inhibitory concentrations against most other coprophilous fungi being at
      or below 100 microg mL(-1). Myrocin B, not previously described from S.
      erythrocephala, was also produced, but only at low, nonfungicidal levels (< 5.3
      microg g(-1)). No other antifungal substances were detected. It is concluded that
      antiamoebins are responsible for antibiosis in dung colonized by S.
      erythrocephala.

PMID- 16420620
TI  - Preferential attack of the (S)-configured ether-linked carbons in bis-(1-chloro-2
      propyl) ether by Rhodococcus sp. strain DTB.
AB  - Rhodococcus sp. strain DTB (DSM 44534) was grown on a mixture of (R,R)-, (S,S)-
      and meso-bis-(1-chloro-2-propyl) ether (BCPE) as the sole source of carbon and
      energy. During BCPE degradation 1'-chloro-2'-propyl-3-chloro-2-prop-1-enyl-ether
      (DVE), 1-chloro-2-propanol and chloroacetone intermediates were formed. The BCPE
      or DVE stereoisomers were metabolized in consecutive order via scission of the
      ether bond, with discrimination against the (R) configuration. Resting cell
      suspensions of Rhodococcus pregrown on BCPE showed a preferential attack of the
      (S)-configured ether-linked carbons, resulting in an enantioselective enrichment
      of (R,R)-BCPE. Microbial discrimination of BCPE or DVE isomers and chemical
      conversion of the intermediates to 1-chloro-2-propanol allowed the identification
      of the configuration of all BCPE isomers and the DVE enantiomers. Elucidation of
      the absolute configuration of the 1-chloro-2-propanol isomers was achieved by
      enantioselective chemical synthesis.

PMID- 16420622
TI  - Host physiological status determines phage-like particle distribution in the
      lysate.
AB  - Bacteriophage morphotype diversity and latent period duration upon induction were
      correlated with the host population growth. The prophages of the lysogenic Vibrio
      sp. (DSM14379) were induced with mitomycin C in a batch culture with different
      salinity, substrate concentration or composition, and at different temperatures.
      Under all experimental conditions, phages were induced and a population of
      different complete and incomplete phage-like particles was observed in the
      lysate. Under favorable growth conditions, the phage-like particle community in
      the lysate was overpopulated with phage tail-like rigid rods. The number of rods
      was reduced in samples with low organic carbon concentration, samples with 8% and
      10% NaCl, and samples induced at 40 and 43 degrees C. Although all lysates
      contained all phage-like particle-size fractions, their relative abundances
      varied. Up to a fivefold difference in phage-like particle size was observed in
      lysates. Size distribution of phage-like particles changed along temperature,
      salinity and organic carbon gradients. Results also indicated that the latent
      period of the induced phage-like particle population converged to approximately
      90 min above a growth rate of 1.0 h(-1). At lower host growth rates, the latent
      period generally increased. However, at 40 and 43 degrees C and at low peptone
      yeast extract concentration in the growth medium, the latent period remained
      short. We propose that different host physiological conditions influence organic
      matter composition upon prophage induction and may thus affect virus-controlled
      flow of the energy and carbon in the ecosystem.

PMID- 16420621
TI  - Effect of bioaugmentation and supplementary carbon sources on degradation of
      polycyclic aromatic hydrocarbons by a soil-derived culture.
AB  - The degradation of polycyclic aromatic hydrocarbons (PAHs) by an undefined
      culture obtained from a PAH-polluted soil and the same culture bioaugmented with
      three PAH-degrading strains was studied in carbon-limited chemostat cultures. The
      PAHs were degraded efficiently by the soil culture and bioaugmentation did not
      significantly improve the PAH degrading performance. The presence of PAHs did,
      however, influence the bacterial composition of the bioaugmented and non
      bioaugmented soil cultures, resulting in the increase in cell concentration of
      sphingomonad strains. the initial enhancement of the degradation of the PAHs by
      biostimulation gradually disappeared and only the presence of salicylate in the
      additional carbon sources had a lasting slightly stimulating effect on the
      degradation of phenanthrene. The results suggest that bioaugmentation and
      biostimulation have limited potential to enhance PAH bioremediation by culture
      already proficient in the degradation of such contaminants.

PMID- 16420623
TI  - Molecular markers detecting an ectomycorrhizal Suillus collinitus strain on Pinus
      halepensis roots suggest successful inoculation and persistence in Mediterranean
      nursery and plantation.
AB  - Survival of the ectomycorrhizal fungal strain Suillus collinitus Sc-32 on Pinus
      halepensis after inoculation and outplanting was monitored in a Mediterranean
      plantation. Three molecular fingerprints were developed: RFLP of the internal
      transcribed spacer ribosomal DNA, intersimple sequence repeat, and a specific
      sequence-characterized amplified region marker. The inoculant was demonstrated to
      survive on inoculated seedlings 4 years after outplanting (56 months after
      inoculation), although S. collinitus was not fruiting. The designed markers set
      allows reliable and inexpensive monitoring of inoculated seedlings and suggests
      that S. collinitus is suitable for inoculation of Mediterranean Pinus. These data
      are discussed in the framework of suilloid population ecology.

PMID- 16420614
TI  - Bacterial diversity in organically-enriched fish farm sediments.
AB  - The bacterial diversity and community structure within both organically enriched
      and adjacent, unimpacted, near-shore marine sediments at two fish farms in
      southern Tasmania, Australia, was examined using 16S rRNA gene clone library
      construction and analysis. Sediments at both caged and reference sites at both
      farms showed a very high level of microbial diversity. Over 900 clones were
      analysed and grouped into 631 unique phylotypes. Reference sites were dominated
      by Delta- and Gammaproteobacteria and the Cytophaga-Flavobacteria-Bacteroides
      group. Cage site sediments were also dominated by these phylotypes, as well as
      members of the Alpha- and Epsilonproteobacteria. Diversity and coverage indices
      indicated that the actual diversity of the sediments was much greater than that
      detected, despite a large sampling effort. All libraries were shown to be
      statistically different from one another (P < 0.05). Many phylotypes did not
      group with cultured bacteria, but grouped with other environmental clones from a
      wide array of marine benthic environments. Diversity and evenness indices
      suggested that although both parameters changed after farming, diverse
      communities were present in all sediments. The response of the microbial
      community to organic load suggested that random, rather than predictable,
      succession events determine community composition and diversity, and that
      sediment type may influence bacterial community and sediment response to organic
      perturbation.

PMID- 16420624
TI  - A digital imaging procedure for seven-probe-labeling FISH (Rainbow-FISH) and its
      application to estuarine microbial communities.
AB  - For multi-probe-labeling fluorescence in situ hybridization (FISH), a digital
      imaging procedure was developed consisting of systematic background noise
      reduction and target signal equalization using a hue, saturation, value color
      partitioning technique. By the combined application of seven DNA probes, each
      labeled with three fluorochromes at maximum, seven kinds of cultured type strains
      were distinguished in a microscopic field simultaneously. Using this seven-probe
      labeling FISH (Rainbow-FISH), several phylogenetic groups of microbes that occur
      frequently in aquatic environments, such as Alpha-, Beta- and
      Gammaproteobacteria, Cytophaga-Flavobacterium and Actinobacteria, were identified
      and quantified. The total counts of cells specified by Rainbow-FISH were in the
      range of 96-108% of those of general FISH, showing that the method is highly
      reliable for quantitative population analysis. Analyzing samples obtained at
      points along a river to a sea, we found a reverse population change in two
      groups: apparent decreases in Betaproteobacteria but gradual increases in
      Gammaproteobacteria. This method provides a platform toward the improvement of
      semiautomatic analysis of aquatic microbes under various metabolic conditions.

PMID- 16420625
TI  - Marine sponges as microbial fermenters.
AB  - The discovery of phylogenetically complex, yet highly sponge-specific microbial
      communities in marine sponges, including novel lineages and even candidate phyla,
      came as a surprise. At the same time, unique research opportunities opened up,
      because the microorganisms of sponges are in many ways more accessible than those
      of seawater. Accordingly, we consider sponges as microbial fermenters that
      provide exciting new avenues in marine microbiology and biotechnology. This
      review covers recent findings regarding diversity, biogeography and population
      dynamics of sponge-associated microbiota, and the data are discussed within the
      larger context of the microbiology of the ocean.

PMID- 16420626
TI  - Nutritive significance of crystalline inclusion proteins of Photorhabdus
      luminescens in Steinernema nematodes.
AB  - Phase I cells of Photorhabdus luminescens produce two types of intracellular
      crystalline inclusion proteins designated CipA and CipB. The genes encoding CipA
      and CipB proteins from P. luminescens H06 were expressed respectively in
      Escherichia coli and these cells were used to feed the axenic first juveniles
      (J1) of three Steinernema nematode isolates in liquid cultures and on agar
      plates. In liquid cultures, the axenic J1 juveniles of all three test Steinernema
      nematode isolates were able to produce next dauer juveniles (DJs) in the E. coli
      cultures with at least one of the expressed Cip proteins, but unable to develop
      beyond the next J1 stage without expressed Cip proteins. For each target nematode
      isolate, addition of the supernatant of the bacterial culture of its Xenorhabdus
      symbiont to the tested liquid cultures did not induce the formation of DJs.
      However, on LB agar plates with different test E. coli cultures, all J1 juveniles
      of the three Steinernema strains finally developed into next DJs. It seemed that
      the metabolite pathway of the test bacteria in both culture systems was
      different. The presence of the Cip proteins has a significant influence on the DJ
      formation of the Steinernema nematodes in liquid culture system.

PMID- 16420627
TI  - Analysis of aerotactic band formation by Desulfovibrio desulfuricans in a stopped
      flow diffusion chamber.
AB  - Aerotactic band formation by Desulfovibrio desulfuricans (DSM 9104) was studied
      in a stopped-flow diffusion chamber. This chamber allowed us to create
      reproducible, steep oxygen gradients in a flat capillary, time-lapse video
      recordings and spatio-temporal analysis of band formation. The cells formed two
      types of bands. Bands of the first type evolved quickly after starting the
      experiment and were located near the oxic-anoxic interface. Bands of the second
      type typically appeared several minutes later and a few millimeters inside the
      initially anoxic volume of the capillary. Band formation depended on metabolism
      and could be stimulated by lactate addition, and thus appears to be energy taxis.
      Mathematical modeling of oxygen diffusion and respiration within the chamber
      revealed that bands formed preferentially at oxygen concentrations close to 4%
      air saturation. The swimming speed of the cells was determined by digital single
      cell tracking and found to be highest (up to 58 mum s(-1)) close to the oxic
      anoxic interfaces. Motility patterns were influenced by surfaces, at which cells
      accumulated. Bioconvection sometimes occurred if very dense bands had formed. The
      ecological implications of these two phenomena are unknown.

PMID- 16420628
TI  - Regulation of photosynthesis and oxygen consumption in a hypersaline
      cyanobacterial mat (Camargue, France) by irradiance, temperature and salinity.
AB  - Short-term effects of irradiance (0-1560 micromol photons m(-2) s(-1)),
      temperature (10-25 degrees C), and salinity (40-160) on oxygenic photosynthesis
      and oxygen consumption in a hypersaline mat (Salin-de-Giraud, France) were
      investigated with microsensors under controlled laboratory conditions. Dark O(2)
      consumption rates were mainly regulated by the mass transfer limitations imposed
      by the diffusive boundary layer. Areal rates of net photosynthesis increased with
      irradiance and saturated at irradiances >400 micromol photons m(-2) s(-1). At low
      irradiances, oxygen consumption increased more strongly with temperature than
      photosynthesis, whereas the opposite was observed at saturating irradiances. Net
      photosynthesis vs. irradiance curves were almost unaffected by decreasing
      salinity (100 to 40), whereas increasing salinities (100 to 160) led to a
      decrease of net photosynthesis at each irradiance. Dark O(2) consumption rates,
      maximal gross and net photosynthesis at light saturation were relatively constant
      over a broad salinity range (60-100) and decreased at salinities above the in
      situ salinity of 100. Within the range of natural variation, temperature was more
      important than salinity in regulating photosynthesis and oxygen consumption. At
      higher salinities the inhibitory impact of salinity on these processes and
      therefore the importance of salinity as a regulating environmental parameter
      increased, indicating that in more hypersaline systems, salinity has a stronger
      limiting effect on microbial activity.

PMID- 16420629
TI  - A microsatellite based method for quantification of fungi in decomposing plant
      material elucidates the role of Fusarium graminearum DON production in the
      saprophytic competition with Trichoderma atroviride in maize tissue microcosms.
AB  - Common PCR assays for quantification of fungi in living plants cannot be used to
      study saprophytic colonization of fungi because plant decomposition releases PCR
      inhibiting substances and saprophytes degrade the plant DNA which could serve as
      internal standard. The microsatellite PCR assays presented here overcome these
      problems by spiking samples prior to DNA extraction with mycelium of a reference
      strain. PCR with fluorescent primers co-amplifies microsatellite fragments of
      different length from target and reference strains. These fragments were
      separated in a capillary sequencer with fluorescence detection. The
      target/reference ratio of fluorescence signal was used to calculate target
      biomass in the sample. Such PCR assays were developed for the mycotoxin
      deoxynivalenol (DON)-producing wheat and maize pathogen Fusarium graminearum and
      the biocontrol agent Trichoderma atroviride, using new microsatellite markers. In
      contrast to real-time PCR assays, the novel PCR assays showed reliable fungal
      biomass quantification in samples with differentially decomposed plant tissue.
      The PCR assays were used to quantify the two fungi after competitive colonization
      of autoclaved maize leaf tissue in microcosms. Using a DON-producing F.
      graminearum wild-type strain and its nontoxigenic mutant we found no evidence for
      a role of DON production in F. graminearum defense against T. atroviride. The
      presence of T. atroviride resulted in a 36% lower wild-type DON production per
      biomass.

PMID- 16420630
TI  - Methanogen communities along a primary succession transect of mire ecosystems.
AB  - Peat accumulating mires are important sources of the greenhouse gas methane.
      Methane emissions and methanogenic Archaea communities have been shown to differ
      between fens and bogs, implying that mire succession includes an ecological
      succession in methanogen communities. We investigated methane production and the
      methanogen communities along a chronosequence of mires (ca. 100-2,500 years),
      which consisted of five sites (1-5) located on the land-uplift coast of the Gulf
      of Bothnia. Methane production was measured in a laboratory incubation
      experiment. Methanogen communities were determined by amplification of a methyl
      coenzyme M-reductase (mcr) gene marker and analyzed by terminal-restriction
      fragment length polymorphism. The terminal-restriction fragment length
      polymorphism fingerprinting resulted in 15 terminal restriction fragments. The
      ordination configuration of the terminal restriction fragments data, using
      nonmetric multidimensional scaling, showed a clear gradient in the methanogen
      community structure along the mire chronosequence. In addition, fingerprint
      patterns of samples from the water table level and 40 cm below differed from one
      another in the bog site (site 5). Methane production was negligible in the three
      youngest fen sites (sites 1-3) and showed the highest rates in the oligotrophic
      fen site (site 4). Successful PCR amplification using mcr gene primers revealed
      the presence of a methanogen community in all five sites along the study
      transect.

PMID- 16420631
TI  - Diversity of the dsrAB (dissimilatory sulfite reductase) gene sequences retrieved
      from two contrasting mudflats of the Seine estuary, France.
AB  - The diversity of sulfate-reducing microorganisms was investigated in two
      contrasting mudflats of the Seine estuary, by PCR amplification, cloning and
      sequencing of the genes coding for parts of the alpha and beta subunits of
      dissimilatory sulfite reductase (dsrAB). One site is located in the mixing-zone
      and shows marine characteristics, with high salinity and sulfate concentration,
      whereas the other site shows freshwater characteristics, with low salinity and
      sulfate concentration. Diversity and abundance of dsrAB genes differed between
      the two sites. In the mixing-zone sediments, most of the dsrAB sequences were
      affiliated to those of marine Gram-negative bacteria belonging to the order of
      Desulfobacterales, whereas in the freshwater sediments, a majority of dsrAB
      sequences was related to those of the Gram-positive bacteria belonging to the
      genus Desulfotomaculum. It is speculated that this is related to the salinity and
      the sulfate concentration in the two mudflats.

PMID- 16420632
TI  - Study of a hexane-degrading consortium in a biofilter and in liquid culture:
      biodiversity, kinetics and characterization of degrading strains.
AB  - A gasoline-degrading consortium, originating from a Mexican soil, was used to
      study its hexane-degradation kinetics in liquid culture and in a biofilter with
      mineral support. The biodiversity of the consortium depending on the culture
      conditions and electron and energy source (gasoline, hexane in liquid or hexane
      in the biofilter) was analyzed using a 16S rRNA-based approach. Significant
      differences between the populations were observed, indicating a probable
      adaptation to the substrate. Two strains, named SP2B and SP72-3, isolated from
      the consortium, belonged to Actinomycetes and demonstrated a high metabolic
      potential in hexane degradation. Even though the SP2B strain was related to
      Rhodococcus ruber DSM 43338(T) by phylogenetic studies, it displayed enlarged
      metabolic properties in hexane and other short-alkane degradation compared with
      the collection strain.

PMID- 16420634
TI  - PCR-DGGE method to assess the diversity of BTEX mono-oxygenase genes at
      contaminated sites.
AB  - tmoA and related genes encode the alpha-subunit of the hydroxylase component of
      the major group (subgroup 1 of subfamily 2) of bacterial multicomponent mono
      oxygenase enzyme complexes involved in aerobic benzene, toluene, ethylbenzene and
      xylene (BTEX) degradation. A PCR-denaturing gradient gel electrophoresis (DGGE)
      method was developed to assess the diversity of tmoA-like gene sequences in
      environmental samples using a newly designed moderately degenerate primer set
      suitable for that purpose. In 35 BTEX-degrading bacterial strains isolated from a
      hydrocarbon polluted aquifer, tmoA-like genes were only detected in two o-xylene
      degraders and were identical to the touA gene of Pseudomonas stutzeri OX1. The
      diversity of tmoA-like genes was examined in DNA extracts from contaminated and
      non-contaminated subsurface samples at a site containing a BTEX-contaminated
      groundwater plume. Differences in DGGE patterns were observed between strongly
      contaminated, less contaminated and non-contaminated samples and between
      different depths, suggesting that the diversity of tmoA-like genes was determined
      by environmental conditions including the contamination level. Phylogenetic
      analysis of the protein sequences deduced from the amplified amplicons showed
      that the diversity of TmoA-analogues in the environment is larger than suggested
      from described TmoA-analogues from cultured isolates, which was translated in the
      DGGE patterns. Although different positions on the DGGE gel can correspond to
      closely related TmoA-proteins, relationships could be noticed between the
      position of tmoA-like amplicons in the DGGE profile and the phylogenetic position
      of the deduced protein sequence.

PMID- 16420633
TI  - The reductive dechlorination of 2,3,4,5-tetrachlorobiphenyl in three different
      sediment cultures: evidence for the involvement of phylogenetically similar
      Dehalococcoides-like bacterial populations.
AB  - Anaerobic cultures capable of reductively dechlorinating 2,3,4,5
      tetrachlorobiphenyl (CB) were enriched from three different sediments, one
      estuarine, one marine and one riverine. Two different electron donors were used
      in enrichments with the estuarine sediment (elemental iron or a mixture of fatty
      acids). The removal of doubly flanked meta and para chlorines to form 2,3,5-CB
      and 2,4,5-CB was observed in all cultures. Bacterial community analysis of PCR
      amplified 16S rRNA gene fragments revealed different communities in these
      cultures, with the exception of one common population that showed a high
      phylogentic relatedness to Dehalococcoides species. No Dehalococcoides-like
      populations were ever detected in control cultures to which no PCBs were added.
      In addition, the dynamics of this Dehalococcoides-like population were strongly
      correlated with dechlorination. Subcultures of the estuarine sediment culture
      demonstrated that the Dehalococcoides-like population disappeared when
      dechlorination was inhibited with 2-bromoethanesulfonate or when 2,3,4,5-CB had
      been consumed. These results provide evidence that Dehalococcoides-like
      populations were involved in the removal of doubly flanked chlorines from 2,3,4,5
      CB. Furthermore, the successful enrichment of these populations from
      geographically distant and geochemically distinct environments indicates the
      widespread presence of these PCB-dechlorinating, Dehalococcoides-like organisms.

PMID- 16420635
TI  - Thauera and Azoarcus as functionally important genera in a denitrifying quinoline
      removal bioreactor as revealed by microbial community structure comparison.
AB  - Structural shifts associated with functional dynamics in a bacterial community
      may provide clues for identifying the most valuable members in an ecosystem. A
      laboratory-scale denitrifying reactor was adapted from use of non-efficient
      seeding sludge and was utilized to degrade quinoline and remove the chemical
      oxygen demand. Stable removal efficiencies were achieved after an adaptation
      period of six weeks. Both denaturing gradient gel electrophoresis profiling of
      the 16S rRNA gene V3 region and comparison of the 16S rRNA gene sequence clone
      libraries (LIBSHUFF analysis) demonstrated that microbial communities in the
      denitrifying reactor and seeding sludge were significantly distinct. The
      percentage of the clones affiliated with the genera Thauera and Azoarcus was 74%
      in the denitrifying reactor and 4% in the seeding sludge. Real-time quantitative
      PCR also indicated that species of the genera Thauera and Azoarcus increased in
      abundance by about one order of magnitude during the period of adaptation. The
      greater abundance of Thauera and Azoarcus in association with higher efficiency
      after adaptation suggested that these phylotypes might play an important role for
      quinoline and chemical oxygen demand removal under denitrifying conditions.

PMID- 16420636
TI  - In-situ enumeration and probing of pyrene-degrading soil bacteria.
AB  - Inferences about which microorganisms degrade polycyclic aromatic hydrocarbons in
      contaminated soils have largely been obtained using culture-based techniques,
      despite the low percentage of microorganisms in soil that are believed to be
      culturable. We used a substrate-responsive direct viable count method to identify
      and quantify potential polycyclic aromatic hydrocarbon-degrading bacteria in a
      soil containing petroleum wastes. Bacteria were extracted and their response to
      substrates determined in the presence of DNA gyrase inhibitors, which cause
      viable and active cells to elongate. When yeast extract, a widely used carbon
      source, was added as a growth substrate, together with nalidixic acid, piromidic
      acid and ciprofloxacin, a significant increase in elongated cells to 47%, 37% and
      22%, respectively, was observed within 24 h. With pyrene as the main substrate,
      10 mg L(-1) of nalidixic acid or piromidic acid caused 18-22% and 8-12%,
      respectively, of the cells to elongate within 24 h; whereas the effect of 0.5 mg
      L(-1) ciprofloxacin was not significant until 53 h later. Enlarged cells were
      identified and enumerated by fluorescent in situ hybridization, using Alpha-,
      Beta- and Gammaproteobacteria, and domain Bacteria-specific probes. The Bacteria
      specific probe detected 35-71% of the total microorganisms detected by the DNA
      binding dye 4,6-diamidino-2-phenylindole. Initially, 44%, 13% and 5% of the total
      bacteria in the soil extract were Alpha-, Beta- and Gammaproteobacteria,
      respectively. Without pyrene or a gyrase inhibitor, these subgroups decreased to
      30% of the total population but were predominant with piromidic acid or unchanged
      with ciprofloxacin when pyrene was the main substrate. The proportion of
      elongated Alpha- and Betaproteobacteria (potential pyrene degraders) increased
      significantly (P<0.05). This approach links phylogenetic information with
      physiological function in situ without the conventional cultivation of bacteria
      and can be used to probe and enumerate degradative groups at even a finer level
      of discrimination.

PMID- 16420637
TI  - Studies on the effect of system retention time on bacterial populations
      colonizing a three-stage continuous culture model of the human large gut using
      FISH techniques.
AB  - Fluorescence in situ hybridization was used to quantitate bacteria growing in a
      three-stage continuous culture system inoculated with human faeces, operated at
      two system retention times (60 and 20 h). Twenty-three different 16S rRNA gene
      oligonucleotide probes of varying specificities were used to detect bacteria.
      Organisms belonging to genera Bacteroides and Bifidobacterium, together with the
      Eubacterium rectale/Clostridium coccoides group, the Atopobium, Faecalibacterium
      prausnitzii and Eubacterium cylindroides groups, as well as the segmented
      filamentous bacteria, the Roseburia intestinalis group and lactic acid bacteria,
      were all present in high numbers in the continuous culture system. Other groups
      and species such as Ruminococci and Enterobacteria also persisted in the model,
      though not always at levels that allowed reliable quantitation. Some organisms
      such as Streptococci and Corynebacteria, present in the faecal inoculum, did not
      colonize the system. Other probes specific for Eubacterium lentum and for members
      of the genus Desulfovibrio did not detect these organisms at any time. Short
      chain fatty acid production was always highest in vessel I of the continuous
      culture system, however, a marked increase in acetate formation and a reduction
      in butyrate production occurred when system retention time was reduced to 20 h,
      which correlated with reductions in the numbers of butyrate-producing Roseburia.

PMID- 16420638
TI  - Seasonal seawater temperature as the major determinant for populations of
      culturable bacteria in the sediments of an intact mangrove in an arid region.
AB  - Mangroves are highly productive marine ecosystems where bacteria (culturable and
      non-culturable) actively participate in biomineralization of organic matter and
      biotransformation of minerals. This study explores spatial and seasonal
      fluctuations of culturable heterotrophic bacteria and Vibrio spp. in the
      sediments of an intact mangrove ecosystem and determines the dominant
      environmental factors that govern these fluctuations. Sediment samples were
      collected monthly from three stations in the mangroves of Laguna de Balandra,
      Baja California Sur, Mexico, through an annual cycle. Physicochemical parameters
      included seawater temperature, salinity, and concentration of dissolved oxygen.
      Viable counts of culturable heterotrophic bacteria and Vibrio spp. were made. In
      one sample (March 2003), nutrient concentrations (ammonium, nitrites, nitrates,
      and phosphates), organic matter, pH and sediment texture were also determined.
      General cluster analyses, analysis of variance of specific variables, and several
      principal component analyses demonstrated that seawater temperature is the
      principal determinant of seasonal distribution of culturable heterotrophic
      bacteria and Vibrio spp. in mangrove sediments. Soil texture, concentration of
      nutrients, and organic matter concentration contribute to heterogenicity to a
      lesser extent. A large spatial variation in bacterial populations was observed
      over short distances ( approximately 1 m) in sampling areas within the same site.
      These analyses show that the culturable bacterial distribution in sediments of
      mangroves has high spatial and temporal heterogeneity.

PMID- 16420639
TI  - Antibiotic resistance of enterococci and related bacteria in an urban wastewater
      treatment plant.
AB  - The main objective of this work was to study the ecology of enterococci and
      related bacteria in raw and treated wastewater from a treatment plant receiving
      domestic and pretreated industrial effluents in order to assess the influence of
      treatment on the prevalence of antibiotic resistance phenotypes among this group
      of bacteria. The predominant species found in the raw wastewater were Entercoccus
      hirae, Entercoccus faecium and Entercoccus faecalis. Wastewater treatment led to
      a reduction in E. hirae (alpha<0.1) and an increase in E. faecium (alpha<0.1);
      the relative proportions of E. faecalis remained the same in the raw and in the
      treated wastewater. Among the isolates tested, no vancomycin resistance was
      observed among the enterococci. Entercoccus faecium and E. faecalis showed
      resistance prevalence values reaching 33%, 40% and 57% for the antibiotics
      ciprofloxacin, erythromycin and tetracycline, respectively. Antibiotic-resistant
      strains of enterococci were not eliminated by wastewater treatment. A positive
      selection of ciprofloxacin-resistant enterococci was indicated by a significant
      increase in resistance prevalence (alpha<0.02) in treated wastewater compared
      with the raw wastewater.

PMID- 16420640
TI  - Surfactant therapy and extracorporeal life support.

PMID- 16420642
TI  - Katrina: an introduction.

PMID- 16420641
TI  - The impact of empiric antimicrobial therapy with a beta-lactam and
      fluoroquinolone on mortality for patients hospitalized with severe pneumonia.
AB  - INTRODUCTION: National clinical practice guidelines have recommended specific
      empiric antimicrobial regimes for patients with severe community-acquired
      pneumonia. However, evidence confirming improved mortality with many of these
      regimes is lacking. Our aim was to determine the association between the empiric
      use of a beta-lactam with fluoroquinolone, compared with other recommended
      antimicrobial therapies, and mortality in patients hospitalized with severe
      community-acquired pneumonia. METHODS: A retrospective observational study was
      conducted at two tertiary teaching hospitals. Eligible subjects were admitted
      with a diagnosis of community-acquired pneumonia and had a chest X-ray and a
      discharge ICD-9 diagnosis consistent with this. Subjects were excluded if they
      received 'comfort measures only' during the admission, had been transferred from
      another acute care hospital, did not meet criteria for severe pneumonia, or were
      treated with non-guideline-concordant antibiotics. A multivariable logistic
      regression model was used to assess the association between 30-day mortality and
      the use of a beta-lactam antibiotic with a fluoroquinolone compared with other
      guideline-concordant therapies, after adjustment for potential confounders
      including a propensity score. RESULTS: Data were abstracted on 172 subjects at
      the two hospitals. The mean age was 63.5 years (SD 15.0). The population was 88%
      male; 91% were admitted through the emergency department and 62% were admitted to
      the intensive care unit within the first 24 hours after admission. Mortality was
      19.8% at 30 days. After adjustment for potential confounders the use of a beta
      lactam with a fluoroquinolone (odds ratio 2.71, 95% confidence interval 1.2 to
      6.1) was associated with increased mortality. CONCLUSION: The use of initial
      empiric antimicrobial therapy with a beta-lactam and a fluoroquinolone was
      associated with increased short-term mortality for patients with severe pneumonia
      in comparison with other guideline-concordant antimicrobial regimes. Further
      research is needed to determine the range of appropriate empiric antimicrobial
      therapies for patients with severe community-acquired pneumonia.

PMID- 16420643
TI  - Falling towers, crumbling levees, and viral mutations.
AB  - Hurricanes Katrina and Rita destroyed an entire beloved city and shattered a
      large part of the US Gulf Coast. Unlike the destruction of 9/11, it is difficult
      to say at the time of this writing whether or not this region will ever be fully
      restored. In light of these and other man-made and natural disasters, the world
      needs to revisit its approach to disaster planning and preparedness to insure
      that we can best meet the needs of those likely to be affected by future
      calamities.

PMID- 16420644
TI  - Practical aspects of federalizing disaster response.

PMID- 16420645
TI  - Disaster preparedness perspective from 90.05.32w, 29.57.18n.
AB  - A major disaster occurred in a major city in the USA. The aftermath produced
      significant difficulties in patient care. Failure of the communication system,
      lack of command and control, and incomplete planning were at the root of all of
      these difficulties.

PMID- 16420646
TI  - Hurricane Katrina--one hospital's experience.
AB  - Hurricane Katrina came ashore in Louisiana at approximately 07:00 hours on
      Monday, 29 August 2005. The storm washed away a swathe of the Louisiana
      coastline, destroyed large portions of the city of New Orleans, and forever
      changed the state of Louisiana. Our Lady of the Lake Regional Medical Center in
      Baton Rouge, Louisiana was one of the receiving hospitals for evacuees from the
      New Orleans area. This commentary briefly describes the hospital's preparation
      before the storm and the activities during and immediately after the storm came
      ashore. Author commentary of the process is included to cover anticipation of the
      patient surge, transport of critical patients, and communication across all
      agencies--interhospital, local, state, and federal. It is beyond the scope of
      this report to judge the performance of agencies outside Our Lady of the Lake
      Hospital.

PMID- 16420648
TI  - Direct patient care during an acute disaster: chasing the will-o'-the-wisp.
AB  - Well developed disaster plans are essential in today's atmosphere of natural and
      man-made disasters. We describe the problems faced by a community hospital on the
      Mississippi Gulf Coast during and in the wake of Hurricane Katrina. Because of
      significant damage to surrounding health care facilities, this hospital was
      called upon to provide care to a large section of the affected population. In
      spite of a previously successful disaster plan, a number of unforeseen
      difficulties were encountered. These included staff shortages due to inability of
      relief personnel to re-enter the affected area, insufficient power generation by
      hospital generators, breakdown in communication, fuel shortage, limited mortuary
      space, and stretching of emergency room resources. These unexpected developments
      emphasize the importance of contingency planning as part of disaster
      preparedness.

PMID- 16420647
TI  - Hurricanes Katrina and Rita: role of individuals and collaborative networks in
      mobilizing/coordinating societal and professional resources for major disasters.
AB  - The medical support for the coordinated effort for Harris County Texas (Houston)
      to rescue evacuees from New Orleans following Hurricane Katrina was part of an
      integrated collaborative network. Both public health and operational health care
      was structured to custom meet the needs of the evacuees and to create an exit
      strategy for the clinic and shelter. Integrating local hospital and physician
      resources into the Joint Incident Command was essential. Outside assistance,
      including federal and national resources must be coordinated through the local
      incident command.

PMID- 16420649
TI  - Disaster and emergency communications prior to computers/Internet: a review.
AB  - When communications are needed the most desperately and most urgently, the
      difficulty of effecting the desired communications increases exponentially.
      Recent natural disasters in different parts of the world have provided eloquent
      testament to this. The history of disaster or emergency communications can
      provide us with a foundation for understanding the problems encountered today,
      and can offer us insight into how we might improve the systems and processes for
      communications. The first applications of communication technology that allowed
      messages to be sent more rapidly than the fastest form of transportation were
      mainly military in origin. This review takes us from the days of optical or
      visual telegraphy, through the early development of mobile and radio
      communications, and up to the current sophisticated technologies. We pay
      particular attention to the use of amateur radio operators in times of emergency,
      and relate their activities to those of the most effective military
      communications. The germane assumption made in this discussion is that any
      emergency or disaster communications would necessarily be involved in response
      and resolution of medical aspects of those emergencies.

PMID- 16420650
TI  - Information technology issues during and after Katrina and usefulness of the
      Internet: how we mobilized and utilized digital communications systems.
AB  - Even more than in previous disasters, Katrina has proven itself to be a testing
      ground for a plethora of new technologies. Although not all of these technologies
      did immediately save lives, in this regard a number of them exhibited
      considerable potential for the future, and hence there is a need to include them
      in future contingency plans. However, a need for change in the modes and patterns
      of technology deployment to maximize their leverage has also become very clear.

PMID- 16420651
TI  - Concluding thoughts on the new nature of disaster management.

PMID- 16420653
TI  - Survival methods, including those using competing risk analysis, are not
      appropriate for intensive care unit outcome studies.
AB  - The preferred analysis for studies of mortality among patients treated in an
      intensive care unit should compare the proportions of patients who died during
      hospitalization. Studies that look for prognostic covariates should use logistic
      regression. Survival methods, such as the proportional hazards model, or methods
      based on competing risk analysis are not appropriate because prolonged survival
      among patients that die during their hospitalization does not benefit the patient
      and, therefore, should not be measured in the statistical analysis.

PMID- 16420652
TI  - Study protocol: The Improving Care of Acute Lung Injury Patients (ICAP) study.
AB  - INTRODUCTION: The short-term mortality benefit of lower tidal volume ventilation
      (LTVV) for patients with acute lung injury/acute respiratory distress syndrome
      (ALI/ARDS) has been demonstrated in a large, multi-center randomized trial.
      However, the impact of LTVV and other critical care therapies on the longer-term
      outcomes of ALI/ARDS survivors remains uncertain. The Improving Care of ALI
      Patients (ICAP) study is a multi-site, prospective cohort study that aims to
      evaluate the longer-term outcomes of ALI/ARDS survivors with a particular focus
      on the effect of LTVV and other critical care therapies. METHODS: Consecutive
      mechanically ventilated ALI/ARDS patients from 11 intensive care units (ICUs) at
      four hospitals in the city of Baltimore, MD, USA, will be enrolled in a
      prospective cohort study. Exposures (patient-based, clinical management, and ICU
      organizational) will be comprehensively collected both at baseline and throughout
      patients' ICU stay. Outcomes, including mortality, organ impairment, functional
      status, and quality of life, will be assessed with the use of standardized
      surveys and testing at 3, 6, 12, and 24 months after ALI/ARDS diagnosis. A multi
      faceted retention strategy will be used to minimize participant loss to follow
      up. RESULTS: On the basis of the historical incidence of ALI/ARDS at the study
      sites, we expect to enroll 520 patients over two years. This projected sample
      size is more than double that of any published study of long-term outcomes in
      ALI/ARDS survivors, providing 86% power to detect a relative mortality hazard of
      0.70 in patients receiving higher versus lower exposure to LTVV. The projected
      sample size also provides sufficient power to evaluate the association between a
      variety of other exposure and outcome variables, including quality of life.
      CONCLUSION: The ICAP study is a novel, prospective cohort study that will build
      on previous critical care research to improve our understanding of the longer
      term impact of ALI/ARDS, LTVV and other aspects of critical care management.
      Given the paucity of information about the impact of interventions on long-term
      outcomes for survivors of critical illness, this study can provide important
      information to inform clinical practice.

PMID- 16420654
TI  - Assisted spontaneous breathing during early acute lung injury.
AB  - In the early phase of their disease process, patients with acute lung injury are
      often ventilated with strategies that control the tidal volume or airway
      pressure, while modes employing spontaneous breathing are applied later to wean
      the patient from the ventilator. Spontaneous breathing modes may integrate
      intrinsic feedback mechanisms that should help prevent ventilator-induced lung
      injury, and should improve synchrony between the ventilator and the patient's
      demand. Airway pressure release ventilation with spontaneous breathing was shown
      to decrease cyclic collapse/recruitment of dependent, juxtadiaphragmatic lung
      areas compared with airway pressure release ventilation without spontaneous
      breathing. Combined with previous data demonstrating improved cardiorespiratory
      variables, airway pressure release ventilation with spontaneous breathing may
      turn out to be a less injurious ventilatory strategy.

PMID- 16420655
TI  - The clinical value of daily routine chest radiographs in a mixed medical-surgical
      intensive care unit is low.
AB  - INTRODUCTION: The clinical value of daily routine chest radiographs (CXRs) in
      critically ill patients is unknown. We conducted this study to evaluate how
      frequently unexpected predefined major abnormalities are identified with daily
      routine CXRs, and how often these findings lead to a change in care for intensive
      care unit (ICU) patients. METHOD: This was a prospective observational study
      conducted in a 28-bed, mixed medical-surgical ICU of a university hospital.
      RESULTS: Over a 5-month period, 2,457 daily routine CXRs were done in 754
      consecutive ICU patients. The majority of these CXRs did not reveal any new
      predefined major finding. In only 5.8% of daily routine CXRs (14.3% of patients)
      was one or more new and unexpected abnormality encountered, including large
      atelectases (24 times in 20 patients), large infiltrates (23 in 22), severe
      pulmonary congestion (29 in 25), severe pleural effusion (13 in 13),
      pneumothorax/pneumomediastinum (14 in 13), and malposition of the orotracheal
      tube (32 in 26). Fewer than half of the CXRs with a new and unexpected finding
      were ultimately clinically relevant; in only 2.2% of all daily routine CXRs (6.4%
      of patients) did these radiologic abnormalities result in a change to therapy.
      Subgroup analysis revealed no differences between medical and surgical patients
      with regard to the incidence of new and unexpected findings on daily routine CXRs
      and the effect of new and unexpected CXR findings on daily care. CONCLUSION: In
      the ICU, daily routine CXRs seldom reveal unexpected, clinically relevant
      abnormalities, and they rarely prompt action. We propose that this diagnostic
      examination be abandoned in ICU patients.

PMID- 16420656
TI  - Erythromycin for prokinesis: imprudent prescribing?
AB  - Problems with antibiotic resistant bacteria are increasing in the hospital and
      particularly in the intensive care unit. Methicillin-resistant Staphylococcus
      aureus, Acinetobacter baumanii and extended spectrum beta-lactamase producing
      gram-negative bacilli constitute a therapeutic and infection control challenge.
      Early enteral feeding improves survival in patients in the intensive care unit.
      Prokinetic agents are routinely used in patients with inappropriate
      gastrointestinal motility. The use of erythromycin at sub-therapeutic doses as a
      prokinetic agent is a cause of concern for the following reasons: it can increase
      the emergence and spread of antibiotic resistance and the likelihood of
      Clostridium difficile disease. The use of an antibiotic as a prokinetic agent
      does not constitute prudent antimicrobial prescribing and should be avoided.
      Alternative agents, whenever possible, should be used.

PMID- 16420658
TI  - Use of prophylactic fluconazole in a neonatal intensive care unit: efficacy is
      similar to that described in adult high-risk surgical patients.

PMID- 16420657
TI  - Changes in appetite related gut hormones in intensive care unit patients: a pilot
      cohort study.
AB  - INTRODUCTION: The nutritional status of patients in the intensive care unit (ICU)
      appears to decline not only during their stay in the ICU but also after discharge
      from the ICU. Recent evidence suggests that gut released peptides, such as
      ghrelin and peptide YY (PYY) regulate the initiation and termination of meals and
      could play a role in the altered eating behaviour of sick patients. The aim of
      this study was to assess the patterns of ghrelin and PYY levels during the stay
      of ICU patients in hospital. METHODS: Sixteen ICU patients (60 +/- 4.7 years,
      body mass index (BMI) 28.1 +/- 1.7 kg/m2 (mean +/- standard error of the mean))
      underwent fasting blood sample collections on days 1, 3, 5, 14, 21 and 28 of
      their stay at Hammersmith and Charing Cross Hospitals. Changes in appetite and
      biochemical and anthropometric markers of nutritional status were recorded. A
      comparison was made to a group of 36 healthy volunteers matched for age and BMI
      (54.3 +/- 2.9 years, p = 0.3; BMI 25.8 +/- 0.8 kg/m2 p = 0.2). RESULTS: Compared
      to healthy subjects, ICU patients exhibited a significantly lower level of
      ghrelin (day one 297.8 +/- 76.3 versus 827.2 +/- 78.7 pmol/l, p < 0.001) during
      their stay in the ICU. This tended to rise to the normal level during the last
      three weeks of hospital stay. Conversely, ICU patients showed a significantly
      higher level of PYY (day one 31.5 +/- 9.6 versus 11.3 +/- 1.0 pmol/l, p < 0.05)
      throughout their stay in the ICU and on the ward, with a downward trend to the
      normal level during the last three weeks of stay. CONCLUSIONS: Results from our
      study show high levels of PYY and low levels of ghrelin in ICU patients compared
      to healthy controls. There appears to be a relationship between the level of
      these gut hormones and nutritional intake.

PMID- 16420659
TI  - Upregulated but insufficient generation of activated protein C is associated with
      development of multiorgan failure in severe acute pancreatitis.
AB  - INTRODUCTION: Disturbed protein C (PC) pathway homeostasis might contribute to
      the development of multiple organ failure (MOF) in acute pancreatitis (AP). We
      therefore evaluated circulating levels of PC and activated protein C (APC),
      evaluated monocyte deactivation in AP patients, and determined the relationship
      of these parameters to MOF. PATIENTS AND METHODS: Thirty-one patients in the
      intensive care unit were categorized as cases (n = 13, severe AP with MOF) or
      controls (n = 18, severe AP without MOF). Blood samples were drawn every second
      day to determine the platelet count, the levels of APC, PC, and D-dimer, and the
      monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to
      evaluate turnover of PC to APC. RESULTS: During the initial two weeks of
      hospitalization, low PC levels (<70% of the adult mean) occurred in 92% of cases
      and 44% of controls (P = 0.008). The minimum APC level was lower in cases than in
      controls (median 85% versus 97%, P = 0.009). Using 87% as the cut-off value, 8/13
      (62%) cases and 3/18 (17%) controls showed reduced APC levels (P = 0.021). A
      total of 92% of cases and 50% of controls had APC/PC ratios exceeding the upper
      normal limit (P = 0.013). Plasma samples drawn before MOF showed low PC levels
      and high APC/PC ratios. HLA-DR-positive monocytes correlated with PC levels (r =
      0.38, P < 0.001) and APC levels (r = 0.27, P < 0.001), indicating that the PC
      pathway was associated with systemic inflammation-triggered immune suppression.
      CONCLUSION: PC deficiency and decreased APC generation in severe AP probably
      contributed to a compromised anticoagulant and anti-inflammatory defence. The PC
      pathway defects were associated with the development of MOF. The data support
      feasibility of testing the use of APC or PC to improve the clinical outcome in
      AP.

PMID- 16420660
TI  - Vasopressin improves outcome in out-of-hospital cardiopulmonary resuscitation of
      ventricular fibrillation and pulseless ventricular tachycardia: a observational
      cohort study.
AB  - INTRODUCTION: An increasing body of evidence from laboratory and clinical studies
      suggests that vasopressin may represent a promising alternative vasopressor for
      use during cardiac arrest and resuscitation. Current guidelines for
      cardiopulmonary resuscitation recommend the use of adrenaline (epinephrine), with
      vasopressin considered only as a secondary option because of limited clinical
      data. METHOD: The present study was conducted in a prehospital setting and
      included patients with ventricular fibrillation or pulseless ventricular
      tachycardia undergoing one of three treatments: group I patients received only
      adrenaline 1 mg every 3 minutes; group II patients received one intravenous dose
      of arginine vasopressin (40 IU) after three doses of 1 mg epinephrine; and
      patients in group III received vasopressin 40 IU as first-line therapy. The cause
      of cardiac arrest (myocardial infarction or other cause) was established for each
      patient in hospital. RESULTS: A total of 109 patients who suffered nontraumatic
      cardiac arrest were included in the study. The rates of restoration of
      spontaneous circulation and subsequent hospital admission were higher in
      vasopressin-treated groups (23/53 [45%] in group I, 19/31 [61%] in group II and
      17/27 [63%] in group III). There were also higher 24-hour survival rates among
      vasopressin-treated patients (P < 0.05), and more vasopressin-treated patients
      were discharged from hospital (10/51 [20%] in group I, 8/31 [26%] in group II and
      7/27 [26%] group III; P = 0.21). Especially in the subgroup of patients with
      myocardial infarction as the underlying cause of cardiac arrest, the hospital
      discharge rate was significantly higher in vasopressin-treated patients (P <
      0.05). Among patients who were discharged from hospital, we found no significant
      differences in neurological status between groups. CONCLUSION: The greater 24
      hour survival rate in vasopressin-treated patients suggests that consideration of
      combined vasopressin and adrenaline is warranted for the treatment of refractory
      ventricular fibrillation or pulseless ventricular tachycardia. This is especially
      the case for those patients with myocardial infarction, for whom vasopressin
      treatment is also associated with a higher hospital discharge rate.

PMID- 16420661
TI  - Hepatic platelet and leukocyte adherence during endotoxemia.
AB  - INTRODUCTION: Liver microcirculation disturbances are a cause of hepatic failure
      in sepsis. Increased leukocyte-endothelial interaction, platelet adherence and
      impaired microperfusion cause hepatocellular damage. The time course and
      reciprocal influences of ongoing microcirculatory events during endotoxemia have
      not been clarified. METHODS: Male Wistar rats (232 +/- 17 g) underwent cecal
      ligation and puncture (CLP). Intravital microscopy (IVM) was performed 0, 1, 3,
      5, 10 and 20 hours after CLP. Mean erythrocyte velocity, leukocyte and platelet
      rolling in postsinusoidal venules and sticking of leukocytes and platelets in
      postsinusoidal venules and hepatic sinusoids were determined. Heart rate (HR),
      mean arterial pressure (MAP) and portal venous blood flow (PBF) were measured.
      Blood count and investigation of hepatic enzyme release was performed after each
      IVM time point. RESULTS: Hepatic platelet-endothelial adherence in liver
      sinusoids and postsinusoidal venules occurred one hour after the induction of
      endotoxemia. Leukocyte-endothelial interaction started three to five hours after
      CLP. A decrease of hepatic microperfusion could be observed at three hours in
      sinusoids and ten hours in postsinusoidal venules after CLP, although PBF was
      reduced one hour after CLP. HR remained stable and MAP decreased ten hours after
      CLP. Hepatic enzymes in blood were significantly elevated ten hours after CLP.
      CONCLUSION: Hepatic platelet-endothelial interaction is an early event during
      endotoxemia. Leukocyte adherence occurs later, which underlines the probable
      involvement of platelets in leukocyte recruitment. Although PBF is reduced
      immediately after CLP, the later onset of hepatic microperfusion decrease makes
      the existence of autoregulatory liver mechanisms likely.

PMID- 16420662
TI  - Acetazolamide-mediated decrease in strong ion difference accounts for the
      correction of metabolic alkalosis in critically ill patients.
AB  - INTRODUCTION: Metabolic alkalosis is a commonly encountered acid-base derangement
      in the intensive care unit. Treatment with the carbonic anhydrase inhibitor
      acetazolamide is indicated in selected cases. According to the quantitative
      approach described by Stewart, correction of serum pH due to carbonic anhydrase
      inhibition in the proximal tubule cannot be explained by excretion of
      bicarbonate. Using the Stewart approach, we studied the mechanism of action of
      acetazolamide in critically ill patients with a metabolic alkalosis. METHODS:
      Fifteen consecutive intensive care unit patients with metabolic alkalosis (pH >
      or = 7.48 and HCO3- > or = 28 mmol/l) were treated with a single administration
      of 500 mg acetazolamide intravenously. Serum levels of strong ions, creatinine,
      lactate, weak acids, pH and partial carbon dioxide tension were measured at 0,
      12, 24, 48 and 72 hours. The main strong ions in urine and pH were measured at 0,
      3, 6, 12, 24, 48 and 72 hours. Strong ion difference (SID), strong ion gap,
      sodium-chloride effect, and the urinary SID were calculated. Data (mean +/-
      standard error were analyzed by comparing baseline variables and time dependent
      changes by one way analysis of variance for repeated measures. RESULTS: After a
      single administration of acetazolamide, correction of serum pH (from 7.49 +/-
      0.01 to 7.46 +/- 0.01; P = 0.001) was maximal at 24 hours and sustained during
      the period of observation. The parallel decrease in partial carbon dioxide
      tension was not significant (from 5.7 +/- 0.2 to 5.3 +/- 0.2 kPa; P = 0.08) and
      there was no significant change in total concentration of weak acids. Serum SID
      decreased significantly (from 41.5 +/- 1.3 to 38.0 +/- 1.0 mEq/l; P = 0.03) due
      to an increase in serum chloride (from 105 +/- 1.2 to 110 +/- 1.2 mmol/l; P <
      0.0001). The decrease in serum SID was explained by a significant increase in the
      urinary excretion of sodium without chloride during the first 24 hours (increase
      in urinary SID: from 48.4 +/- 15.1 to 85.3 +/- 7.7; P = 0.02). CONCLUSION: A
      single dose of acetazolamide effectively corrects metabolic alkalosis in
      critically ill patients by decreasing the serum SID. This effect is completely
      explained by the increased renal excretion ratio of sodium to chloride, resulting
      in an increase in serum chloride.

PMID- 16420664
TI  - PAC-Man: game over for the pulmonary artery catheter?

PMID- 16420663
TI  - Inhaled beta-2 agonist salbutamol and acute lung injury: an association with
      improvement in acute lung injury.
AB  - INTRODUCTION: Beta2 agonists have several properties that could be beneficial in
      acute lung injury (ALI). We therefore chose to study the effect of inhaled beta2
      agonist use (salbutamol) on duration and severity of ALI. METHODS: We undertook a
      retrospective chart review of 86 consecutive mechanically ventilated patients
      with ALI, who had varying exposure to inhaled salbutamol. The cohort was divided
      into two groups according to the average daily dose of inhaled salbutamol they
      received ('high dose' > or = 2.2 mg/day and 'low dose' < 2.2 mg/day). Severity of
      ALI and non-pulmonary organ dysfunction was compared between the groups by
      calculating the days alive and free of ALI and other organ dysfunctions. RESULTS:
      The high dose and low dose groups received a mean of 3.72 mg and 0.64 mg
      salbutamol per day, respectively. The high dose salbutamol group had
      significantly more days alive and free of ALI than the low dose group (12.2 +/-
      4.4 days versus 7.6 +/- 1.9 days, p = 0.02). There were no associations between
      dose of beta agonist and non-pulmonary organ dysfunctions. High dose salbutamol
      (p = 0.04), APACHE II score (p = 0.02), and cause of ALI (p = 0.02) were
      independent variables associated with number of days alive and free of ALI in a
      multivariate linear regression model. CONCLUSION: Our retrospective study
      suggests that salbutamol, an inhaled beta2 agonist, is associated with a shorter
      duration and lower severity of ALI. A dose greater than 2.2 mg/day of inhaled
      salbutamol could be a minimal effective dose to evaluate in a randomized
      controlled trial.

PMID- 16420665
TI  - Early recombinant activated factor VII for intracerebral hemorrhage reduced
      hematoma growth and mortality, while improving functional outcomes.

PMID- 16420666
TI  - Levosimendan may improve survival in patients requiring mechanical assist devices
      for post-cardiotomy heart failure.
AB  - INTRODUCTION: Most case series suggest that less than half of the patients
      receiving a mechanical cardiac assist device as a bridge to recovery due to
      severe post-cardiotomy heart failure survive to hospital discharge. Levosimendan
      is the only inotropic substance known to improve medium term survival in patients
      suffering from severe heart failure. METHODS: This retrospective analysis covers
      our single centre experience. Between July 2000 and December 2004, 41 consecutive
      patients were treated for this complication. Of these, 38 patients are included
      in this retrospective analysis as 3 patients died in the operating room.
      Levosimendan was added to the treatment protocol for the last nine patients.
      RESULTS: Of 29 patients treated without levosimendan, 20 could be weaned off the
      device, 9 survived to intensive care unit discharge, 7 left hospital alive and 3
      survived 180 days. All 9 patients treated with levosimendan could be weaned, 8
      were discharged alive from ICU and hospital, and 7 lived 180 days after surgery
      (p < 0.002 for 180 day survival). Plasma lactate after explantation of the device
      was significantly lower (p = 0.002), as were epinephrine doses. Time spent on
      renal replacement therapy was significantly shorter (p = 0.023). CONCLUSION:
      Levosimendan seems to improve medium term survival in patients failing to wean
      off cardiopulmonary bypass and requiring cardiac assist devices as a bridge to
      recovery. This retrospective analysis justifies prospective randomised
      investigations of levosimendan in this group of patients.

PMID- 16420667
TI  - Primary and secondary transcriptional effects in the developing human Down
      syndrome brain and heart.
AB  - BACKGROUND: Down syndrome, caused by trisomic chromosome 21, is the leading
      genetic cause of mental retardation. Recent studies demonstrated that dosage
      dependent increases in chromosome 21 gene expression occur in trisomy 21.
      However, it is unclear whether the entire transcriptome is disrupted, or whether
      there is a more restricted increase in the expression of those genes assigned to
      chromosome 21. Also, the statistical significance of differentially expressed
      genes in human Down syndrome tissues has not been reported. RESULTS: We measured
      levels of transcripts in human fetal cerebellum and heart tissues using DNA
      microarrays and demonstrated a dosage-dependent increase in transcription across
      different tissue/cell types as a result of trisomy 21. Moreover, by having a
      larger sample size, combining the data from four different tissue and cell types,
      and using an ANOVA approach, we identified individual genes with significantly
      altered expression in trisomy 21, some of which showed this dysregulation in a
      tissue-specific manner. We validated our microarray data by over 5,600
      quantitative real-time PCRs on 28 genes assigned to chromosome 21 and other
      chromosomes. Gene expression values from chromosome 21, but not from other
      chromosomes, accurately classified trisomy 21 from euploid samples. Our data also
      indicated functional groups that might be perturbed in trisomy 21. CONCLUSIONS:
      In Down syndrome, there is a primary transcriptional effect of disruption of
      chromosome 21 gene expression, without a pervasive secondary effect on the
      remaining transcriptome. The identification of dysregulated genes and pathways
      suggests molecular changes that may underlie the Down syndrome phenotypes.

PMID- 16420669
TI  - The expression signature of in vitro senescence resembles mouse but not human
      aging.
AB  - BACKGROUND: The biological mechanisms that underlie aging have not yet been fully
      identified. Senescence, a phenomenon occurring in vitro, limits the number of
      cell divisions in mammalian cell cultures and has been suggested to contribute to
      aging. RESULTS: We investigated whether the changes in gene expression that occur
      during mammalian aging and induction of cellular senescence are similar. We
      compared changes of gene expression in seven microarray datasets from aging
      human, mouse and rat, as well as four microarray datasets from senescent cells of
      man and mouse. The datasets were publicly available or obtained from other
      laboratories. Correlation measures were used to establish similarities of the
      expression profiles and gene ontology analyses to identify functional groups of
      genes that are co-regulated. Robust similarities were established between aging
      in different species and tissues, indicating that there is an aging
      transcriptome. Although some cross-species comparisons displayed high
      correlation, intra-species similarities were more reliable. Similarly, a
      senescence transcriptome was demonstrated that is conserved across cell types. A
      similarity between the expression signatures of cellular senescence and aging
      could be established in mouse, but not in human. CONCLUSION: Our study is the
      first to use microarray data from several studies and laboratories for dissection
      of a complex biological phenotype. We demonstrate the presence of a mammalian
      aging transcriptome, and discuss why similarity between cellular senescence and
      aging is apparent in aging mice only.

PMID- 16420668
TI  - Molecular processes during fat cell development revealed by gene expression
      profiling and functional annotation.
AB  - BACKGROUND: Large-scale transcription profiling of cell models and model
      organisms can identify novel molecular components involved in fat cell
      development. Detailed characterization of the sequences of identified gene
      products has not been done and global mechanisms have not been investigated. We
      evaluated the extent to which molecular processes can be revealed by expression
      profiling and functional annotation of genes that are differentially expressed
      during fat cell development. RESULTS: Mouse microarrays with more than 27,000
      elements were developed, and transcriptional profiles of 3T3-L1 cells (pre
      adipocyte cells) were monitored during differentiation. In total, 780
      differentially expressed expressed sequence tags (ESTs) were subjected to in
      depth bioinformatics analyses. The analysis of 3'-untranslated region sequences
      from 395 ESTs showed that 71% of the differentially expressed genes could be
      regulated by microRNAs. A molecular atlas of fat cell development was then
      constructed by de novo functional annotation on a sequence segment/domain-wise
      basis of 659 protein sequences, and subsequent mapping onto known pathways,
      possible cellular roles, and subcellular localizations. Key enzymes in 27 out of
      36 investigated metabolic pathways were regulated at the transcriptional level,
      typically at the rate-limiting steps in these pathways. Also, coexpressed genes
      rarely shared consensus transcription-factor binding sites, and were typically
      not clustered in adjacent chromosomal regions, but were instead widely dispersed
      throughout the genome. CONCLUSIONS: Large-scale transcription profiling in
      conjunction with sophisticated bioinformatics analyses can provide not only a
      list of novel players in a particular setting but also a global view on
      biological processes and molecular networks.

PMID- 16420670
TI  - A compendium of Caenorhabditis elegans regulatory transcription factors: a
      resource for mapping transcription regulatory networks.
AB  - BACKGROUND: Transcription regulatory networks are composed of interactions
      between transcription factors and their target genes. Whereas unicellular
      networks have been studied extensively, metazoan transcription regulatory
      networks remain largely unexplored. Caenorhabditis elegans provides a powerful
      model to study such metazoan networks because its genome is completely sequenced
      and many functional genomic tools are available. While C. elegans gene
      predictions have undergone continuous refinement, this is not true for the
      annotation of functional transcription factors. The comprehensive identification
      of transcription factors is essential for the systematic mapping of transcription
      regulatory networks because it enables the creation of physical transcription
      factor resources that can be used in assays to map interactions between
      transcription factors and their target genes. RESULTS: By computational searches
      and extensive manual curation, we have identified a compendium of 934
      transcription factor genes (referred to as wTF2.0). We find that manual curation
      drastically reduces the number of both false positive and false negative
      transcription factor predictions. We discuss how transcription factor splice
      variants and dimer formation may affect the total number of functional
      transcription factors. In contrast to mouse transcription factor genes, we find
      that C. elegans transcription factor genes do not undergo significantly more
      splicing than other genes. This difference may contribute to differences in
      organism complexity. We identify candidate redundant worm transcription factor
      genes and orthologous worm and human transcription factor pairs. Finally, we
      discuss how wTF2.0 can be used together with physical transcription factor clone
      resources to facilitate the systematic mapping of C. elegans transcription
      regulatory networks. CONCLUSION: wTF2.0 provides a starting point to decipher the
      transcription regulatory networks that control metazoan development and function.

PMID- 16420671
TI  - Systematic analysis of gene expression in human brains before and after death.
AB  - BACKGROUND: Numerous studies have employed microarray techniques to study changes
      in gene expression in connection with human disease, aging and evolution. The
      vast majority of human samples available for research are obtained from deceased
      individuals. This raises questions about how well gene expression patterns in
      such samples reflect those of living individuals. RESULTS: Here, we compare gene
      expression patterns in two human brain regions in postmortem samples and in
      material collected during surgical intervention. We find that death induces
      significant expression changes in more than 10% of all expressed genes. These
      changes are non-randomly distributed with respect to their function. Moreover, we
      observe similar expression changes due to death in two distinct brain regions.
      Consequently, the pattern of gene expression differences between the two brain
      regions is largely unaffected by death, although the magnitude of differences is
      reduced by 50% in postmortem samples. Furthermore, death-induced changes do not
      contribute significantly to gene expression variation among postmortem human
      brain samples. CONCLUSION: We conclude that postmortem human brain samples are
      suitable for investigating gene expression patterns in humans, but that caution
      is warranted in interpreting results for individual genes.

PMID- 16420672
TI  - A novel approach to identifying regulatory motifs in distantly related genomes.
AB  - Although proven successful in the identification of regulatory motifs,
      phylogenetic footprinting methods still show some shortcomings. To assess these
      difficulties, most apparent when applying phylogenetic footprinting to distantly
      related organisms, we developed a two-step procedure that combines the advantages
      of sequence alignment and motif detection approaches. The results on well-studied
      benchmark datasets indicate that the presented method outperforms other methods
      when the sequences become either too long or too heterogeneous in size.

PMID- 16420674
TI  - iVici: Interrelational Visualization and Correlation Interface.
AB  - We have developed an application, iVici, to analyze cellular networks represented
      as addressable symmetric or asymmetric two-dimensional matrices. iVici was
      designed to permit simultaneous visualization and correlation of multiple
      datasets, representing any relationship between a set of genes, mRNAs, or
      proteins. Visual overlay of datasets and addressable access to gene annotations
      permits comparison of networks of different types (for example protein-protein
      interactions and genetic networks) or investigation of the dynamic reorganization
      of a particular network.

PMID- 16420675
TI  - New approaches to combating antimicrobial drug resistance.
AB  - Recent work shows that the inhibition of the SOS stress response in Escherichia
      coli reduces the development of resistance to the antibiotics ciprofloxacin and
      rifampicin. This finding may help in the battle against the rise of resistance to
      antimicrobial drugs.

PMID- 16420673
TI  - Discovery of biological networks from diverse functional genomic data.
AB  - We have developed a general probabilistic system for query-based discovery of
      pathway-specific networks through integration of diverse genome-wide data. This
      framework was validated by accurately recovering known networks for 31 biological
      processes in Saccharomyces cerevisiae and experimentally verifying predictions
      for the process of chromosomal segregation. Our system, bioPIXIE, a public,
      comprehensive system for integration, analysis, and visualization of biological
      network predictions for S. cerevisiae, is freely accessible over the worldwide
      web.

PMID- 16420677
TI  - New developments in developmental biology.
AB  - A report on the 15th International Society of Developmental Biologists Congress,
      Sydney, Australia, 3-7 September 2005.

PMID- 16420676
TI  - The AP-2 family of transcription factors.
AB  - The AP-2 family of transcription factors consists of five different proteins in
      humans and mice: AP-2alpha, AP-2beta, AP-2gamma, AP-2delta and AP-2epsilon. Frogs
      and fish have known orthologs of some but not all of these proteins, and homologs
      of the family are also found in protochordates, insects and nematodes. The
      proteins have a characteristic helix-span-helix motif at the carboxyl terminus,
      which, together with a central basic region, mediates dimerization and DNA
      binding. The amino terminus contains the transactivation domain. AP-2 proteins
      are first expressed in primitive ectoderm of invertebrates and vertebrates; in
      vertebrates, they are also expressed in the emerging neural-crest cells, and AP
      2alpha-/- animals have impairments in neural-crest-derived facial structures. AP
      2beta is indispensable for kidney development and AP-2gamma is necessary for the
      formation of trophectoderm cells shortly after implantation; AP-2alpha and AP
      2gamma levels are elevated in human mammary carcinoma and seminoma. The general
      functions of the family appear to be the cell-type-specific stimulation of
      proliferation and the suppression of terminal differentiation during embryonic
      development.

PMID- 16420680
TI  - Foxes and hounds.

PMID- 16420681
TI  - Recent developments in membrane-protein structural genomics.
AB  - Recent work has identified the topology of almost all the inner membrane proteins
      in Escherichia coli, and advances in nuclear magnetic resonance spectroscopy now
      allow the determination of alpha-helical membrane protein structures at high
      resolution. Together these developments will help overcome the current
      limitations of high-throughput determination of membrane protein structures.

PMID- 16420682
TI  - The regulation of endocytosis by kinases: cell biology meets genomics.
AB  - The mechanisms of signal transduction and vesicular transport have traditionally
      been studied in isolation, but recent studies make it clear that the two
      processes are inextricably linked. A new genome-wide analysis of human kinases
      using RNA interference shows an unexpected depth and complexity to the
      interactions between these processes.

PMID- 16420683
TI  - From single cells to whole organisms.
AB  - A report on the European Science Foundation Conference 'Functional Genomics and
      Disease', Oslo, Norway, 6-10 September 2005.

PMID- 16420678
TI  - The undertranslated transcriptome reveals widespread translational silencing by
      alternative 5' transcript leaders.
AB  - BACKGROUND: Translational efficiencies in Saccharomyces cerevisiae vary from
      transcript to transcript by approximately two orders of magnitude. Many of the
      poorly translated transcripts were found to respond to the appropriate external
      stimulus by recruiting ribosomes. Unexpectedly, a high frequency of these
      transcripts showed the appearance of altered 5' leaders that coincide with
      increased ribosome loading. RESULTS: Of the detectable transcripts in S.
      cerevisiae, 8% were found to be underloaded with ribosomes. Gene ontology
      categories of responses to stress or external stimuli were overrepresented in
      this population of transcripts. Seventeen poorly loaded transcripts involved in
      responses to pheromone, nitrogen starvation, and osmotic stress were selected for
      detailed study and were found to respond to the appropriate environmental signal
      with increased ribosome loading. Twelve of these regulated transcripts exhibited
      structural changes in their 5' transcript leaders in response to the
      environmental signal. In many of these the coding region remained intact, whereas
      regulated shortening of the 5' end truncated the open reading frame in others.
      Colinearity between the gene and transcript sequences eliminated regulated
      splicing as a mechanism for these alterations in structure. CONCLUSION: Frequent
      occurrence of coordinated changes in transcript structure and translation
      efficiency, in at least three different gene regulatory networks, suggests a
      widespread phenomenon. It is likely that many of these altered 5' leaders arose
      from changes in promoter usage. We speculate that production of translationally
      silenced transcripts may be one mechanism for allowing low-level transcription
      activity necessary for maintaining an open chromatin structure while not allowing
      inappropriate protein production.

PMID- 16420684
TI  - Unraveling prion structures and biological functions.
AB  - A report on a Joint Cold Spring Harbor Laboratory/Wellcome Trust Conference on
      'Prion Biology', Hinxton, UK, 7-11 September 2005.

PMID- 16420687
TI  - Ineffective off-label use of recombinant activated factor VII in a case of bone
      marrow transplantation-related gastrointestinal bleeding.
AB  - BACKGROUND: For patients with a normal coagulation system, who experience serious
      bleeding, sound evidence for recombinant activated factor VII (rFVIIa) as an
      effective haemostatic agent is only scarcely available so far from controlled
      clinical trials. In systematic reviews on the clinical use of rFVIIa, treatment
      failures were only rarely reported. CASE PRESENTATION: We present a 45-year old,
      Caucasian male with persistent intestinal bleeding due to enterocolitis
      associated with cytomegalovirus infection and acute graft-versus-host-disease. He
      had received allogeneic peripheral blood stem cell transplantation from an
      unrelated HLA-identical donor because of chronic myelogenous leukaemia diagnosed
      two years earlier. Bleeding started at day 18 after transplantation with bloody
      diarrhea, which was treated with multiple transfusions of fresh frozen plasma,
      platelet, and red blood cell concentrates, and continued relentlessly, despite
      all efforts, including continued transfusions, high-dose prednisolone, broad
      antibiotic and antiviral coverage, and tranexamic acid. Recombinant FVIIa was
      started at boluses of 90-120 mug/kg every 4-8 hours. Despite more than 10 doses,
      recurrent severe bleeding progressed to refractory shock, multiorgan failure and
      death. CONCLUSIONS: Little can be concluded from single case reports of clinical
      improvement, because publication bias in favour of positive effects is likely.
      Our case suggests that rFVIIa is not a panacea, in particular for severe bleeding
      after bone-marrow transplantation. As long as rigorous, controlled studies or
      comprehensive registries are lacking, conventional interventions remain the
      standard of care in non-haemophilic patients with severe bleeding.

PMID- 16420686
TI  - Real-time quantitative PCR with SYBR Green I detection for estimating copy
      numbers of nine drug resistance candidate genes in Plasmodium falciparum.
AB  - BACKGROUND: Evaluating copy numbers of given genes in Plasmodium falciparum
      parasites is of major importance for laboratory-based studies or epidemiological
      surveys. For instance, pfmdr1 gene amplification has been associated with
      resistance to quinine derivatives and several genes involved in anti-oxidant
      defence may play an important role in resistance to antimalarial drugs, although
      their potential involvement has been overlooked. METHODS: The DeltaDeltaCt method
      of relative quantification using real-time quantitative PCR with SYBR Green I
      detection was adapted and optimized to estimate copy numbers of three genes
      previously indicated as putative candidates of resistance to quinolines and
      artemisinin derivatives: pfmdr1, pfatp6 (SERCA) and pftctp, and in six further
      genes involved in oxidative stress responses. RESULTS: Using carefully designed
      specific RT-qPCR oligonucleotides, the methods were optimized for each gene and
      validated by the accurate measure of previously known number of copies of the
      pfmdr1 gene in the laboratory reference strains P. falciparum 3D7 and Dd2.
      Subsequently, Standard Operating Procedures (SOPs) were developed to the
      remaining genes under study and successfully applied to DNA obtained from dried
      filter blood spots of field isolates of P. falciparum collected in Sao Tome &
      Principe, West Africa. CONCLUSION: The SOPs reported here may be used as a high
      throughput tool to investigate the role of these drug resistance gene candidates
      in laboratory studies or large scale epidemiological surveys.

PMID- 16420688
TI  - A molecular signature of epithelial host defense: comparative gene expression
      analysis of cultured bronchial epithelial cells and keratinocytes.
AB  - BACKGROUND: Epithelia are barrier-forming tissues that protect the organism
      against external noxious stimuli. Despite the similarity in function of
      epithelia, only few common protective mechanisms that are employed by these
      tissues have been systematically studied. Comparative analysis of genome-wide
      expression profiles generated by means of Serial Analysis of Gene Expression
      (SAGE) is a powerful approach to yield further insight into epithelial host
      defense mechanisms. We performed an extensive comparative analysis of previously
      published SAGE data sets of two types of epithelial cells, namely bronchial
      epithelial cells and keratinocytes, in which the response to pro-inflammatory
      cytokines was assessed. These data sets were used to elucidate a common
      denominator in epithelial host defense. RESULTS: Bronchial epithelial cells and
      keratinocytes were found to have a high degree of overlap in gene expression.
      Using an in silico approach, an epithelial-specific molecular signature of gene
      expression was identified in bronchial epithelial cells and keratinocytes
      comprising of family members of keratins, small proline-rich proteins and
      proteinase inhibitors. Whereas some of the identified genes were known to be
      involved in inflammation, the majority of the signature represented genes that
      were previously not associated with host defense. Using polymerase chain
      reaction, presence of expression of selected tissue-specific genes was validated.
      CONCLUSION: Our comparative analysis of gene transcription reveals that bronchial
      epithelial cells and keratinocytes both express a subset of genes that is likely
      to be essential in epithelial barrier formation in these cell types. The
      expression of these genes is specific for bronchial epithelial cells and
      keratinocytes and is not seen in non-epithelial cells. We show that bronchial
      epithelial cells, similar to keratinocytes, express components that are able to
      form a cross-linked protein envelope that may contribute to an effective barrier
      against noxious stimuli and pathogens.

PMID- 16420689
TI  - Memory in astrocytes: a hypothesis.
AB  - BACKGROUND: Recent work has indicated an increasingly complex role for astrocytes
      in the central nervous system. Astrocytes are now known to exchange information
      with neurons at synaptic junctions and to alter the information processing
      capabilities of the neurons. As an extension of this trend a hypothesis was
      proposed that astrocytes function to store information. To explore this idea the
      ion channels in biological membranes were compared to models known as cellular
      automata. These comparisons were made to test the hypothesis that ion channels in
      the membranes of astrocytes form a dynamic information storage device. RESULTS:
      Two dimensional cellular automata were found to behave similarly to ion channels
      in a membrane when they function at the boundary between order and chaos. The
      length of time information is stored in this class of cellular automata is
      exponentially related to the number of units. Therefore the length of time
      biological ion channels store information was plotted versus the estimated number
      of ion channels in the tissue. This analysis indicates that there is an
      exponential relationship between memory and the number of ion channels.
      Extrapolation of this relationship to the estimated number of ion channels in the
      astrocytes of a human brain indicates that memory can be stored in this system
      for an entire life span. Interestingly, this information is not affixed to any
      physical structure, but is stored as an organization of the activity of the ion
      channels. Further analysis of two dimensional cellular automata also demonstrates
      that these systems have both associative and temporal memory capabilities.
      CONCLUSION: It is concluded that astrocytes may serve as a dynamic information
      sink for neurons. The memory in the astrocytes is stored by organizing the
      activity of ion channels and is not associated with a physical location such as a
      synapse. In order for this form of memory to be of significant duration it is
      necessary that the ion channels in the astrocyte syncytium be electrically in
      contact with each other. This function may be served by astrocyte gap junctions
      and suggests that agents that selectively block these gap junctions should
      disrupt memory.

PMID- 16420691
TI  - Orthodontic treatment needs in the western region of Saudi Arabia: a research
      report.
AB  - BACKGROUND: Evaluation of self perceived and actual need for orthodontic
      treatment helps in planning orthodontic services and estimating the required
      resources and man power. In the present study, the perceptive need as evaluated
      by patients and the actual need to orthodontic treatment, as assessed by
      orthodontists, were evaluated at two types of dental practices in the city of
      Jeddah using the Index of Orthodontic Treatment Need (IOTN). METHODS: A
      consecutive sample of 743 adults seeking orthodontic treatment at two different
      types of dental practices in Jeddah; King Abdulaziz University, Faculty of
      Dentistry (KAAU) (Free treatment) and two private dental polyclinics (PDP) (Paid
      treatment), was examined for orthodontic treatment need using the dental health
      component (DHC) of the IOTN. The self-perceived need for orthodontic treatment
      was also determined using the aesthetic component (AC) of the IOTN. The IOTN
      score and the incidence of each variable were calculated statistically. AC and
      DHC categories were compared using the Chi-Square and a correlation between them
      was assessed using Spearman's correlation test. AC and DHC were also compared
      between the two types of dental practices using the Chi-Square. RESULTS: The
      results revealed that among the 743 patients studied, 60.6% expressed no or
      slight need for treatment, 23.3% expressed moderate to borderline need and
      only16.1% thought they needed orthodontic treatment. Comparing these estimates to
      professional judgments, only 15.2% conformed to little or no need for treatment,
      13.2% were assessed as in borderline need and 71.6% were assessed as in need for
      treatment (p < 0.001). Spearman's correlation test proved no correlation (r = 
      .045) between the two components. Comparing the AC and the DHC between the KAAU
      group and PDP group showed significant differences between the two groups (p <
      0.001). CONCLUSION: Patient's perception to orthodontic treatment does not always
      correlate with professional assessment. The IOTN is a valid screening tool that
      should be used in orthodontic clinics for better services especially, in health
      centers that provide free treatment.

PMID- 16420692
TI  - Changes in caseload and the potential impact on surgical training: a
      retrospective review of one hospital's experience.
AB  - BACKGROUND: Recent reforms to the training grades have provoked debate about both
      quality and quantity of training. The bulk of previous research into this area
      has been qualitative, and little is known about the quantity of training
      opportunities. This study aimed to determine if the number of elective operations
      available to trainees was stable. METHODS: The number of elective procedures
      carried out in each surgical specialty (General & Vascular Surgery, Urology,
      Orthopaedics, ENT) in a large district general hospital was analysed in 6 month
      periods and adjusted for the number of basic surgical trainees in each specialty.
      In order to allow comparison between specialties, results for each 6 month period
      were calculated as a percentage of those for the first period. RESULTS: The
      number of elective operations available per trainee fell in 3 of the 4
      specialties, with a rise in Orthopaedics. Overall, the number of operations
      available to each trainee was 56% of that less than a decade ago. CONCLUSION: The
      number of operations available in a conventional hospital setting is decreasing.
      Introduction of the Modernizing Medical Careers reforms must take account of this
      if they are to succeed in improving the quality of surgical training.

PMID- 16420690
TI  - The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa.
AB  - BACKGROUND: An organ such as the bladder consists of complex, interacting set of
      tissues and cells. Inflammation has been implicated in every major disease of the
      bladder, including cancer, interstitial cystitis, and infection. However, scanty
      is the information about individual detrusor and urothelium transcriptomes in
      response to inflammation. Here, we used suppression subtractive hybridizations
      (SSH) to determine bladder tissue- and disease-specific genes and transcriptional
      regulatory elements (TRE)s. Unique TREs and genes were assembled into putative
      networks. RESULTS: It was found that the control bladder mucosa presented
      regulatory elements driving genes such as myosin light chain phosphatase and
      calponin 1 that influence the smooth muscle phenotype. In the control detrusor
      network the Pax-3 TRE was significantly over-represented. During development, the
      Pax-3 transcription factor (TF) maintains progenitor cells in an undifferentiated
      state whereas, during inflammation, Pax-3 was suppressed and genes involved in
      neuronal development (synapsin I) were up-regulated. Therefore, during
      inflammation, an increased maturation of neural progenitor cells in the muscle
      may underlie detrusor instability. NF-kappaB was specifically over-represented in
      the inflamed mucosa regulatory network. When the inflamed detrusor was compared
      to control, two major pathways were found, one encoding synapsin I, a neuron
      specific phosphoprotein, and the other an important apoptotic protein, siva. In
      response to LPS-induced inflammation, the liver X receptor was over-represented
      in both mucosa and detrusor regulatory networks confirming a role for this
      nuclear receptor in LPS-induced gene expression. CONCLUSION: A new approach for
      understanding bladder muscle-urothelium interaction was developed by assembling
      SSH, real time PCR, and TRE analysis results into regulatory networks.
      Interestingly, some of the TREs and their downstream transcripts originally
      involved in organogenesis and oncogenesis were also activated during
      inflammation. The latter represents an additional link between inflammation and
      cancer. The regulatory networks represent key targets for development of novel
      drugs targeting bladder diseases.

PMID- 16420693
TI  - The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing
      apoptosis in MCF-7 breast cancer cells.
AB  - BACKGROUND: DAL-1 (Differentially Expressed in Adenocarcinoma of the Lung)/4.1B
      is a member of the protein 4.1 superfamily that has been shown to suppress growth
      in lung, breast and brain tumor cells. In the case of the caspase-3 deficient MCF
      7 breast cancer cells, this growth suppression has been shown to be partially
      mediated by the induction of apoptosis. However the exact mechanism of action of
      DAL-1/4.1B is unknown. Recently, protein arginine N-methyltransferase 3 (PRMT3)
      was identified as a DAL-1/4.1B interacting protein. Protein arginine
      methyltransferases (PRMTs) posttranslationally methylate the arginine residues of
      proteins, a modification which has been implicated in the regulation of multiple
      cellular processes including nuclear-cytoplasmic transport, signal transduction,
      and transcription. RESULTS: To investigate the role of protein methylation in
      cell death induced by DAL-1/4.1B, DAL-1/4.1B-inducible MCF-7 cells were examined
      for apoptosis and caspase activation in the absence and presence of the protein
      methylation inhibitor adenosine dialdehyde (AdOX). Flow cytometry analysis
      revealed that apoptosis was primarily associated with the activation of caspase
      8, and inhibition of this activation blocked the ability of DAL-1/4.1B to induce
      cell death. CONCLUSION: These results suggest that protein methylation cooperates
      with DAL-1/4.1B-associated caspase 8-specific activation to induce apoptosis in
      breast cancer cells.

PMID- 16420695
TI  - Quantitative ultrasound tissue characterization in shoulder and thigh muscles--a
      new approach.
AB  - BACKGROUND: The echogenicity patterns of ultrasound scans contain information of
      tissue composition in muscles. The aim was: (1) to develop a quantitative
      ultrasound image analysis to characterize tissue composition in terms of
      intensity and structure of the ultrasound images, and (2) to use the method for
      characterization of ultrasound images of the supraspinatus muscle, and the vastus
      lateralis muscle. METHODS: Computerized texture analyses employing first-order
      and higher-order grey-scale statistics were developed to objectively characterize
      ultrasound images of m. supraspinatus and m. vastus lateralis from 9 healthy
      participants. RESULTS: The mean grey-scale intensity was higher in the vastus
      lateralis muscle (p < 0.05) than in the supraspinatus muscle (average value of
      middle measuring site 51.4 compared to 35.0). Furthermore, the number of
      spatially connected and homogeneous regions (blobs) was higher in the vastus
      lateralis (p < 0.05) than in the supraspinatus (average for m. vastus lateralis:
      0.092 mm(-2) and for m. supraspinatus: 0.016 mm(-2)). CONCLUSION: The higher
      intensity and the higher number of blobs in the vastus lateralis muscle indicates
      that the thigh muscle contained more non-contractile components than the
      supraspinatus muscle, and that the muscle was coarser. The image analyses
      supplemented each other and gave a more complete description of the tissue
      composition in the muscle than the mean grey-scale value alone.

PMID- 16420694
TI  - Analysis and visualization of chromosomal abnormalities in SNP data with SNPscan.
AB  - BACKGROUND: A variety of diseases are caused by chromosomal abnormalities such as
      aneuploidies (having an abnormal number of chromosomes), microdeletions,
      microduplications, and uniparental disomy. High density single nucleotide
      polymorphism (SNP) microarrays provide information on chromosomal copy number
      changes, as well as genotype (heterozygosity and homozygosity). SNP array studies
      generate multiple types of data for each SNP site, some with more than 100,000
      SNPs represented on each array. The identification of different classes of
      anomalies within SNP data has been challenging. RESULTS: We have developed
      SNPscan, a web-accessible tool to analyze and visualize high density SNP data. It
      enables researchers (1) to visually and quantitatively assess the quality of user
      generated SNP data relative to a benchmark data set derived from a control
      population, (2) to display SNP intensity and allelic call data in order to detect
      chromosomal copy number anomalies (duplications and deletions), (3) to display
      uniparental isodisomy based on loss of heterozygosity (LOH) across genomic
      regions, (4) to compare paired samples (e.g. tumor and normal), and (5) to
      generate a file type for viewing SNP data in the University of California, Santa
      Cruz (UCSC) Human Genome Browser. SNPscan accepts data exported from Affymetrix
      Copy Number Analysis Tool as its input. We validated SNPscan using data generated
      from patients with known deletions, duplications, and uniparental disomy. We also
      inspected previously generated SNP data from 90 apparently normal individuals
      from the Centre d'Etude du Polymorphisme Humain (CEPH) collection, and identified
      three cases of uniparental isodisomy, four females having an apparently mosaic X
      chromosome, two mislabelled SNP data sets, and one microdeletion on chromosome 2
      with mosaicism from an apparently normal female. These previously unrecognized
      abnormalities were all detected using SNPscan. The microdeletion was
      independently confirmed by fluorescence in situ hybridization, and a region of
      homozygosity in a UPD case was confirmed by sequencing of genomic DNA.
      CONCLUSION: SNPscan is useful to identify chromosomal abnormalities based on SNP
      intensity (such as chromosomal copy number changes) and heterozygosity data
      (including regions of LOH and some cases of UPD). The program and source code are
      available at the SNPscan website
      http://pevsnerlab.kennedykrieger.org/snpscan.htm.

PMID- 16420696
TI  - Metabolic pathways variability and sequence/networks comparisons.
AB  - BACKGROUND: In this work a simple method for the computation of relative
      similarities between homologous metabolic network modules is presented. The
      method is similar to classical sequence alignment and allows for the generation
      of phenotypic trees amenable to be compared with correspondent sequence based
      trees. The procedure can be applied to both single metabolic modules and whole
      metabolic network data without the need of any specific assumption. RESULTS: We
      demonstrate both the ability of the proposed method to build reliable biological
      classification of a set of microorganisms and the strong correlation between the
      metabolic network wiring and involved enzymes sequence space. CONCLUSION: The
      method represents a valuable tool for the investigation of genotype/phenotype
      correlations allowing for a direct comparison of different species as for their
      metabolic machinery. In addition the detection of enzymes whose sequence space is
      maximally correlated with the metabolic network space gives an indication of the
      most crucial (on an evolutionary viewpoint) steps of the metabolic process.

PMID- 16420697
TI  - Real-time PCR complements immunohistochemistry in the determination of HER-2/neu
      status in breast cancer.
AB  - BACKGROUND: The clinical benefit of determining the status of HER-2/neu
      amplification in breast cancer patients is well accepted. Although
      immunohistochemistry (IHC) is the most frequently used method to assess the over
      expression of HER-2 protein, fluorescent in-situ hybridization (FISH) is
      recognized as the "gold standard" for the determining of HER-2/neu status. The
      greatest discordance between the two methods occurs among breast tumors that
      receive an indeterminate IHC score of 2+. More recently, a real-time polymerase
      chain reaction (PCR) assay using the LightCycler(R) has been developed for
      quantifying HER-2/neu gene amplification. In this study, we evaluated the
      sensitivity and specificity of a commercially available LightCycler assay as it
      compares to FISH. To determine whether this assay provides an accurate
      alternative for the determination of HER-2/neu status, we focused primarily on
      tumors that were deemed indeterminate or borderline status by IHC. METHODS:
      Thirty-nine breast tumors receiving an IHC score of 2+ were evaluated by both
      FISH and LightCycler(R) technologies in order to determine whether quantitative
      real-time PCR provides an accurate alternative for the determination of HER-2/neu
      status. RESULTS: We found a high concordance (92%) between FISH and real-time PCR
      results. We also observed that 10% of these tumors were positive for gene
      amplification by both FISH and real-time PCR. CONCLUSION: The data show that the
      results obtained for the gene amplification of HER-2/neu by real-time PCR on the
      LightCycler instrument is comparable to results obtained by FISH. These results
      therefore suggest that real-time PCR analysis, using the LightCycler, is a viable
      alternative to FISH for reassessing breast tumors which receive an IHC score of
      2+, and that a combined IHC and real-time PCR approach for the determination of
      HER-2 status in breast cancer patients may be an effective and efficient
      strategy.

PMID- 16420699
TI  - Web GIS in practice IV: publishing your health maps and connecting to remote WMS
      sources using the Open Source UMN MapServer and DM Solutions MapLab.
AB  - Open Source Web GIS software systems have reached a stage of maturity,
      sophistication, robustness and stability, and usability and user friendliness
      rivalling that of commercial, proprietary GIS and Web GIS server products. The
      Open Source Web GIS community is also actively embracing OGC (Open Geospatial
      Consortium) standards, including WMS (Web Map Service). WMS enables the creation
      of Web maps that have layers coming from multiple different remote
      servers/sources. In this article we present one easy to implement Web GIS server
      solution that is based on the Open Source University of Minnesota (UMN)
      MapServer. By following the accompanying step-by-step tutorial instructions,
      interested readers running mainstream Microsoft(R) Windows machines and with no
      prior technical experience in Web GIS or Internet map servers will be able to
      publish their own health maps on the Web and add to those maps additional layers
      retrieved from remote WMS servers. The 'digital Asia' and 2004 Indian Ocean
      tsunami experiences in using free Open Source Web GIS software are also briefly
      described.

PMID- 16420700
TI  - Plasma D-dimer concentration in patients with systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder of the connective
      tissue characterized by widespread vascular lesions and fibrosis. Little is known
      so far on the activation of the hemostatic and fibrinolytic systems in SSc, and
      most preliminary evidences are discordant. METHODS: To verify whether SSc
      patients might display a prothrombotic condition, plasma D-dimer was assessed in
      28 consecutive SSc patients and in 33 control subjects, matched for age, sex and
      environmental habit. RESULTS AND DISCUSSION: When compared to healthy controls,
      geometric mean and 95% confidence interval (IC95%) of plasma D-dimer were
      significantly increased in SSc patients (362 ng/mL, IC 95%: 361-363 ng/mL vs 229
      ng/mL, IC95%: 228-231 ng/mL, p = 0.005). After stratifying SSc patients according
      to disease subset, no significant differences were observed between those with
      limited cutaneous pattern and controls, whereas patients with diffuse cutaneous
      pattern displayed substantially increased values. No correlation was found
      between plasma D-dimer concentration and age, sex, autoantibody pattern, serum
      creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and
      pulmonary involvement. CONCLUSION: We demonstrated that SSc patients with diffuse
      subset are characterized by increased plasma D-dimer values, reflecting a
      potential activation of both the hemostatic and fibrinolytic cascades, which
      might finally predispose these patients to thrombotic complications.

PMID- 16420701
TI  - Malaria vectors in Angola: distribution of species and molecular forms of the
      Anopheles gambiae complex, their pyrethroid insecticide knockdown resistance
      (kdr) status and Plasmodium falciparum sporozoite rates.
AB  - BACKGROUND: Malaria is by far the greatest cause of morbidity and mortality in
      Angola, being responsible for 50% of all outpatient attendance and around 22% of
      all hospital deaths, yet by 2003 only 2% of under-5s used insecticide-treated
      nets. Entomological studies are an essential foundation for rational malaria
      control using insecticide-treated nets and indoor residual spraying, but there
      have been no published studies of malaria vectors in Angola over the 27 years of
      the civil war, to its end in 2002. This paper describes studies arising from a
      WHO-sponsored visit in support of the National Malaria Control Programme.
      METHODS: During April 2001, mosquitoes were sampled by indoor pyrethrum spray
      collection from four sites in the semi-arid coastal provinces of Luanda and
      Benguela and two sites in Huambo province, in the humid tropical highlands.
      Collections took place towards the end of the rainy season and were used to
      determine the Anopheles species present, their sporozoite rates and the frequency
      of a kdr allele conferring resistance to pyrethroid insecticides. RESULTS: A PCR
      test for the Anopheles gambiae complex showed a preponderance of An. gambiae,
      with indoor resting densities ranging from 0.9 to 23.5 per house. Of 403 An.
      gambiae identified to molecular form, 93.5% were M-form and 6.5% S-form. M and S
      were sympatric at 4 sites but no M/S hybrids were detected. The highest
      proportion of S-form (20%) was in samples from Huambo, in the humid highlands.
      Anopheles funestus was found at one site near Luanda. The sporozoite rate of
      mosquitoes, determined by an ELISA test, was 1.9% for An. gambiae (n = 580) and
      0.7% for An. funestus (n = 140). Of 218 An. gambiae (195 M-form and 23 S-form)
      genotyped for the West African kdr-resistance allele, all were homozygous
      susceptible. CONCLUSION: An. gambiae M-form is the most important and widespread
      malaria vector in the areas studied but more extensive studies of malaria vectors
      are required to support the malaria control programme in Angola. These should
      include standard insecticide resistance biossays and molecular assays that can
      detect both metabolic resistance and target site insensitivity.

PMID- 16420702
TI  - Multi-level analyses of spatial and temporal determinants for dengue infection.
AB  - BACKGROUND: Dengue is a mosquito-borne viral infection that is now endemic in
      most tropical countries. In Thailand, dengue fever/dengue hemorrhagic fever is a
      leading cause of hospitalization and death among children. A longitudinal study
      among 1750 people in two rural and one urban sites in northern Thailand from 2001
      to 2003 studied spatial and temporal determinants for recent dengue infection at
      three levels (time, individual and household). METHOD: Determinants for dengue
      infection were measured by questionnaire, land-cover maps and GIS. IgM antibodies
      against dengue were detected by ELISA. Three-level multi-level analysis was used
      to study the risk determinants of recent dengue infection. RESULTS: Rates of
      recent dengue infection varied substantially in time from 4 to 30%, peaking in
      2002. Determinants for recent dengue infection differed per site. Spatial
      clustering was observed, demonstrating variation in local infection patterns.
      Most of the variation in recent dengue infection was explained at the time-period
      level. Location of a person and the environment around the house (including
      irrigated fields and orchards) were important determinants for recent dengue
      infection. CONCLUSION: We showed the focal nature of asymptomatic dengue
      infections. The great variation of determinants for recent dengue infection in
      space and time should be taken into account when designing local dengue control
      programs.

PMID- 16420703
TI  - Eleven ancestral gene families lost in mammals and vertebrates while otherwise
      universally conserved in animals.
AB  - BACKGROUND: Gene losses played a role which may have been as important as gene
      and genome duplications and rearrangements, in modelling today species' genomes
      from a common ancestral set of genes. The set and diversity of protein-coding
      genes in a species has direct output at the functional level. While gene losses
      have been reported in all the major lineages of the metazoan tree of life, none
      have proposed a focus on specific losses in the vertebrates and mammals lineages.
      In contrast, genes lost in protostomes (i.e. arthropods and nematodes) but still
      present in vertebrates have been reported and extensively detailed. This probable
      over-anthropocentric way of comparing genomes does not consider as an important
      phenomena, gene losses in species that are usually described as "higher". However
      reporting universally conserved genes throughout evolution that have recently
      been lost in vertebrates and mammals could reveal interesting features about the
      evolution of our genome, particularly if these losses can be related to losses of
      capability. RESULTS: We report 11 gene families conserved throughout eukaryotes
      from yeasts (such as Saccharomyces cerevisiae) to bilaterian animals (such as
      Drosophila melanogaster or Caenorhabditis elegans). This evolutionarily wide
      conservation suggests they were present in the last common ancestors of fungi and
      metazoan animals. None of these 11 gene families are found in human nor mouse
      genomes, and their absence generally extends to all vertebrates. A total of 8 out
      of these 11 gene families have orthologs in plants, suggesting they were present
      in the Last Eukaryotic Common Ancestor (LECA). We investigated known functional
      information for these 11 gene families. This allowed us to correlate some of the
      lost gene families to loss of capabilities. CONCLUSION: Mammalian and vertebrate
      genomes lost evolutionary conserved ancestral genes that are probably otherwise
      not dispensable in eukaryotes. Hence, the human genome, which is generally viewed
      as being the result of increased complexity and gene-content, has also evolved
      through simplification and gene losses. This acknowledgement confirms, as already
      suggested, that the genome of our far ancestor was probably more complex than
      ever considered.

PMID- 16420704
TI  - Risk factors for traumatic and non-traumatic lower limb pain among
      preadolescents: a population-based study of Finnish schoolchildren.
AB  - BACKGROUND: The child's lower limb is the most commonly reported musculoskeletal
      location with pain and also the most commonly injured site in sports. Some
      potential risk factors have been studied, but the results are inconsistent. We
      hypothesized that distinction of traumatic from non-traumatic pain would provide
      a clearer picture of these factors. The aim of this study is to assess factors
      associated with lower extremity pain and its impact on preadolescents in a
      population-based cohort. METHODS: A structured pain questionnaire was completed
      by 1756 schoolchildren of third and fifth grades to assess musculoskeletal pain,
      psychosomatic symptoms, subjective disabilities, school absence and frequency of
      exercise. In addition, hypermobility and physical fitness were measured. RESULTS:
      The knee was the most common site of pain followed by the ankle-foot and thigh.
      Of the children who reported pain in their lower extremity, approximately 70%
      reported at least one disability and 19% reported school absence attributed to
      their pain during the previous three-month period. Children with traumatic pain
      had a higher subjective disability index than those with non-traumatic pain (P =
      0.02). Age less than 11 years, headache, abdominal pain, depressive feelings, day
      tiredness, and vigorous exercise were more common in children with lower limb
      pain than those free of it. In the stratified analysis, younger age was related
      to both traumatic and non-traumatic pain groups. Vigorous exercise was positively
      associated with traumatic pain, while subjects with non-traumatic pain had more
      frequent psychosomatic symptoms. CONCLUSION: Risk factors and consequences of
      traumatic and non-traumatic lower limb pain are not similar. Traumatic lower limb
      pain is associated with practicing vigorous exercise and high level of physical
      fitness, while non-traumatic pain is more correlated with psychosomatic symptoms.
      These differences might be one of the reasons for the discrepancy of previous
      research conclusions. The two conditions need to be treated as different
      disorders in future studies.

PMID- 16420705
TI  - Discovery of Time-Delayed Gene Regulatory Networks based on temporal gene
      expression profiling.
AB  - BACKGROUND: It is one of the ultimate goals for modern biological research to
      fully elucidate the intricate interplays and the regulations of the molecular
      determinants that propel and characterize the progression of versatile life
      phenomena, to name a few, cell cycling, developmental biology, aging, and the
      progressive and recurrent pathogenesis of complex diseases. The vast amount of
      large-scale and genome-wide time-resolved data is becoming increasing available,
      which provides the golden opportunity to unravel the challenging reverse
      engineering problem of time-delayed gene regulatory networks. RESULTS: In
      particular, this methodological paper aims to reconstruct regulatory networks
      from temporal gene expression data by using delayed correlations between genes,
      i.e., pairwise overlaps of expression levels shifted in time relative each other.
      We have thus developed a novel model-free computational toolbox termed TdGRN
      (Time-delayed Gene Regulatory Network) to address the underlying regulations of
      genes that can span any unit(s) of time intervals. This bioinformatics toolbox
      has provided a unified approach to uncovering time trends of gene regulations
      through decision analysis of the newly designed time-delayed gene expression
      matrix. We have applied the proposed method to yeast cell cycling and human HeLa
      cell cycling and have discovered most of the underlying time-delayed regulations
      that are supported by multiple lines of experimental evidence and that are
      remarkably consistent with the current knowledge on phase characteristics for the
      cell cyclings. CONCLUSION: We established a usable and powerful model-free
      approach to dissecting high-order dynamic trends of gene-gene interactions. We
      have carefully validated the proposed algorithm by applying it to two publicly
      available cell cycling datasets. In addition to uncovering the time trends of
      gene regulations for cell cycling, this unified approach can also be used to
      study the complex gene regulations related to the development, aging and
      progressive pathogenesis of a complex disease where potential dependences between
      different experiment units might occurs.

PMID- 16420706
TI  - Quality of life and pain in premenopausal women with major depressive disorder:
      the POWER Study.
AB  - BACKGROUND: Whereas it is established that organic pain may induce depression, it
      is unclear whether pain is more common in healthy subjects with depression. We
      assessed the prevalence of pain in premenopausal women with major depression
      (MDD). Subjects were 21- to 45-year-old premenopausal women with MDD (N = 70;
      age: 35.4 +/- 6.6; mean +/- SD) and healthy matched controls (N = 36; age 35.4 +/
      6.4) participating in a study of bone turnover, the P.O.W.E.R. (Premenopausal,
      Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study. METHODS: Patients
      received a clinical assessment by a pain specialist, which included the
      administration of two standardized forms for pain, the Brief Pain Inventory -
      Short Form, and the Initial Pain Assessment Tool, and two scales of everyday
      stressors, the Hassles and Uplifts Scales. In addition, a quality-of-life
      instrument, the SF-36, was used. The diagnosis of MDD was established by a semi
      structured interview, according to the DSM-IV criteria. Substance P (SP) and
      calcitonin-gene-related-peptide (CGRP), neuropeptides which are known mediators
      of pain, were measured every hour for 24 h in a subgroup of patients (N = 17) and
      controls (N = 14). RESULTS: Approximately one-half of the women with depression
      reported pain of mild intensity. Pain intensity was significantly correlated with
      the severity of depression (r2 = 0.076; P = 0.04) and tended to be correlated
      with the severity of anxiety, (r2 = 0.065; P = 0.07), and the number of
      depressive episodes (r2 = 0.072; P = 0.09). Women with MDD complained of fatigue,
      insomnia, and memory problems and experienced everyday negative stressors more
      frequently than controls. Quality of life was decreased in women with depression,
      as indicated by lower scores in the emotional and social well-being domains of
      the SF-36. SP (P < 0.0003) and CGRP (P < 0.0001) were higher in depressed
      subjects. CONCLUSION: Women with depression experienced pain more frequently than
      controls, had a lower quality of life, and complained more of daily stressors.
      Assessment of pain may be important in the clinical evaluation of women with MDD.
      SP and CGRP may be useful biological markers in women with MDD.

PMID- 16420707
TI  - Diversity begets diversity: host expansions and the diversification of plant
      feeding insects.
AB  - BACKGROUND: Plant-feeding insects make up a large part of earth's total
      biodiversity. While it has been shown that herbivory has repeatedly led to
      increased diversification rates in insects, there has been no compelling
      explanation for how plant-feeding has promoted speciation rates. There is a
      growing awareness that ecological factors can lead to rapid diversification and,
      as one of the most prominent features of most insect-plant interactions,
      specialization onto a diverse resource has often been assumed to be the main
      process behind this diversification. However, specialization is mainly a pruning
      process, and is not able to actually generate diversity by itself. Here we
      investigate the role of host colonizations in generating insect diversity, by
      testing if insect speciation rate is correlated with resource diversity. RESULTS:
      By applying a variant of independent contrast analysis, specially tailored for
      use on questions of species richness (MacroCAIC), we show that species richness
      is strongly correlated with diversity of host use in the butterfly family
      Nymphalidae. Furthermore, by comparing the results from reciprocal sister group
      selection, where sister groups were selected either on the basis of diversity of
      host use or species richness, we find that it is likely that diversity of host
      use is driving species richness, rather than vice versa. CONCLUSION: We conclude
      that resource diversity is correlated with species richness in the Nymphalidae
      and suggest a scenario based on recurring oscillations between host expansions -
      the incorporation of new plants into the repertoire - and specialization, as an
      important driving force behind the diversification of plant-feeding insects.

PMID- 16420708
TI  - Use and traditional management of Anadenanthera colubrina (Vell.) Brenan in the
      semi-arid region of northeastern Brazil.
AB  - The use and management of "angico" (Anadenanthera colubrina (Vell.) Brenan) by a
      rural community in northeastern Brazil was examined. By employing different
      techniques of data collection and population structure analysis, it was
      determined that this species had multiple uses within the local community
      (especially as timber and for other wood products), and that local management of
      this species is based on simple maintenance and harvesting of individuals in
      agroforest homegardens. The study of the population structure of this tree
      species indicated that management and conservation strategies must include the
      participation of the local community.

PMID- 16420709
TI  - Clinical features and outcome of sporadic serogroup W135 disease Taiwan.
AB  - BACKGROUND: Few published reports have evaluated the clinical features and
      outcome of serogroup W135 meningococcal disease. In Taiwan, W135 is the second
      most prevalent meningococcal disease serogroup. METHOD: A nationwide study was
      conducted to retrospectively analyze epidemiologic data from 115 patients with
      laboratory confirmed meningococcal disease that occurred from 2001 through 2003.
      RESULTS: Serogroup W135 accounted for 26% of all cases and most (76.7%) were
      older than 20 years. There were no cases of serogroup W135 meningococcal disease
      associated with Hajj pilgrims, and all cases were sporadic. In 88 patients with
      complete case records, we compared the presenting symptoms, signs, laboratory
      data, and outcomes between W135 and non-W135 patients. There were no differences
      in presenting symptoms except for the higher prevalence of pneumonia found in
      W135 patients (23.8% vs. 1.5%; OR: 20.6; 95%CI: 2.3-189.0; p = 0.003). The
      distribution of inflammatory cells in CSF in patients with meningitis was also
      different between W135 and non-W135 patients. W135 patients had a trend toward
      more intubations and shock but it did not achieve statistical significance. In
      multivariate analysis of factors associated with death, three independent factors
      were found: bacteremia without meningitis, altered mental status, and petechiae
      or purpura on admission. CONCLUSION: Sporadic serogroup W135 meningococcal
      disease is an important component of the meningococcal disease burden in Taiwan,
      but it is not directly associated with Hajj pilgrims. Compared with patients
      infected by other serogroups of meningococci, patients with serogroup W135 were
      older and more likely to have extrameningeal involvement such as pneumonia.

PMID- 16420711
TI  - The association between suicide and the socio-economic characteristics of
      geographical areas: a systematic review.
AB  - BACKGROUND: Despite an extensive literature, there have been widely divergent
      findings regarding the direction of the association between area socio-economic
      characteristics and area suicide rates, with high-quality studies finding either
      a direct relation (higher rates of suicide in higher socio-economic areas), an
      inverse relation (lower rates of suicide in higher socio-economic areas) or no
      association. METHOD: We performed a systematic review of the literature dating
      from 1897 to 2004 and identified 86 publications with 221 separate analyses that
      met our inclusion criteria. We examined the percent of direct, inverse and null
      findings stratified by key study characteristics including size of aggregated
      area, socio-economic measure used, region of study, control variables and study
      design. RESULTS: Analyses at the community level are significantly more likely to
      demonstrate lower rates of suicide among higher socio-economic areas than studies
      using larger areas of aggregation. Measures of area poverty and deprivation are
      most likely to be inversely associated with suicide rates and median income is
      least likely to be inversely associated with suicide rates. Analyses using
      measures of unemployment and education and occupation were equally likely to
      demonstrate inverse associations. Study results did not vary significantly by
      gender or by study design. CONCLUSIONS: The heterogeneity of associations is
      mostly accounted for by study design features that have largely been neglected in
      this literature. Enhanced attention to size of region and measurement strategies
      provide a clearer picture of how suicide rates vary by region. Resources for
      suicide prevention should be targeted to high poverty/deprivation and high
      unemployment areas.

PMID- 16420712
TI  - The age-dependent decline of attention deficit hyperactivity disorder: a meta
      analysis of follow-up studies.
AB  - BACKGROUND: This study examined the persistence of attention deficit
      hyperactivity disorder (ADHD) into adulthood. METHOD: We analyzed data from
      published follow-up studies of ADHD. To be included in the analysis, these
      additional studies had to meet the following criteria: the study included a
      control group and it was clear from the methods if the diagnosis of ADHD included
      subjects who did not meet full criteria but showed residual and impairing signs
      of the disorder. We used a meta-analysis regression model to separately assess
      the syndromatic and symptomatic persistence of ADHD. RESULTS: When we define only
      those meeting full criteria for ADHD as having 'persistent ADHD', the rate of
      persistence is low, approximately 15% at age 25 years. But when we include cases
      consistent with DSM-IV's definition of ADHD in partial remission, the rate of
      persistence is much higher, approximately 65%. CONCLUSIONS: Our results show that
      estimates of ADHD's persistence rely heavily on how one defines persistence. Yet,
      regardless of definition, our analyses show that evidence for ADHD lessens with
      age. More work is needed to determine if this reflects true remission of ADHD
      symptoms or is due to the developmental insensitivity of diagnostic criteria for
      the disorder.

PMID- 16420713
TI  - Young adult outcome of attention deficit hyperactivity disorder: a controlled 10
      year follow-up study.
AB  - BACKGROUND: Our objective was to estimate the lifetime prevalence of
      psychopathology in a sample of youth with and without attention deficit
      hyperactivity disorder (ADHD) through young adulthood using contemporaneous
      diagnostic and analytic techniques. METHOD: We conducted a case-control, 10-year
      prospective study of ADHD youth. At baseline, we assessed consecutively referred
      male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6
      18 years, ascertained from psychiatric and pediatric sources to allow for
      generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of
      the ADHD and control children, respectively, were reassessed (mean age 22 years).
      We created the following categories of psychiatric disorders: Major
      Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial
      Disorders (conduct, oppositional-defiant, and antisocial personality disorder),
      Developmental Disorders (elimination, language, and tics disorder), and Substance
      Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by
      blinded structured diagnostic interview. RESULTS: The lifetime prevalence for all
      categories of psychopathology were significantly greater in ADHD young adults
      compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5
      10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0),
      respectively, for the categories described above. CONCLUSIONS: By their young
      adult years, ADHD youth were at high risk for a wide range of adverse psychiatric
      outcomes including markedly elevated rates of antisocial, addictive, mood and
      anxiety disorders. These prospective findings provide further evidence for the
      high morbidity associated with ADHD across the life-cycle and stress the
      importance of early recognition of this disorder for prevention and intervention
      strategies.

PMID- 16420714
TI  - Suicidal behaviour among primary-care patients with depressive disorders.
AB  - BACKGROUND: Most national suicide prevention strategies set improved detection
      and management of depression in primary health care into a central position.
      However, suicidal behaviour among primary-care patients with depressive disorders
      has been seldom investigated. METHOD: In the Vantaa Primary Care Depression
      Study, a total of 1119 primary-care patients in the City of Vantaa, Finland, aged
      20 to 69 years, were screened for depression with the Primary Care Evaluation of
      Mental Disorders (PRIME-MD) questionnaire. Depressive disorders were diagnosed
      with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and
      the 137 patients with depressive disorder were included in the study. Suicidal
      behaviour was investigated cross-sectionally and retrospectively in three time
      frames: current, current depressive episode, and lifetime. Current suicidal
      ideation was measured with the Scale for Suicidal Ideation (SSI), and previous
      ideation and suicide attempts were evaluated based on interviews plus medical and
      psychiatric records. RESULTS: Within their lifetimes, 37% (51/137) of the
      patients had seriously considered suicide and 17% (23/137) attempted it. Lifetime
      suicidal behaviour was independently and strongly predicted by psychiatric
      treatment history and co-morbid personality disorder, and suicidal behaviour
      within the current episode was predicted most effectively by severity of
      depression. CONCLUSIONS: Based on these findings and their convergence with
      studies of completed suicides, prevention of suicidal behaviour in primary care
      should probably focus more on high-risk subgroups of depressed patients,
      including those with moderate to severe major depressive disorder, personality
      disorder or a history of psychiatric care. Recognition of suicidal behaviour
      should be improved. The complex psychopathology of these patients in primary care
      needs to be considered in targeting preventive efforts.

PMID- 16420715
TI  - Psychiatric morbidity is related to parental age: a national cohort study.
AB  - BACKGROUND: The median age at first childbirth has increased dramatically in many
      high-income countries during the past decades. The psychiatric consequences of
      this demographic change are insufficiently described on a population level. This
      study aimed to investigate whether parental age at childbearing is related to
      psychiatric morbidity among Swedish youths. METHOD: This was a cohort study based
      on Swedish national registers. A national cohort of 292129 children born to
      primiparas women during 1973-1979 was followed prospectively from 1987 to 2002 in
      registers. Multivariate Cox analyses of proportional hazards were used to
      estimate the relative risk of hospital admission for schizophrenia, alcohol and
      illicit drug abuse, suicide attempts and deaths. RESULTS: Youths born of teenage
      mothers had a high risk for suicide death [relative risk (RR) 1.9, 95% confidence
      interval (CI) 1.3-2.7] and hospital admissions because of suicide attempt (RR
      2.0, 95% CI 1.7-2.3) and substance abuse (alcohol: RR 1.6, 95% CI 1.4-1.8;
      illicit drug: RR 2.2, 95% CI 1.9-2.5) after adjustments for major
      sociodemographic confounders, compared with children of mothers aged 25-29 years.
      Offspring of older parents (>34 years) had the highest risk for schizophrenia (RR
      1.8, 95% CI 1.0-3.0). CONCLUSIONS: Parental age is related to psychiatric
      morbidity.

PMID- 16420717
TI  - Sodium-myo-inositol co-transporter (SMIT-1) mRNA is increased in neutrophils of
      patients with bipolar 1 disorder and down-regulated under treatment with mood
      stabilizers.
AB  - Recent in-vitro data indicate that depletion of neural cells of myo-inositol by
      virtue of down-regulation of the high-affinity sodium-myo-inositol co-transporter
      (SMIT) may be a common mechanism of action of the mood stabilizers lithium,
      valproate and carbamazepine. The authors sought to investigate whether or not
      down-regulation of SMIT also occurs in vivo in bipolar patients. Expression of
      SMIT mRNA was measured in neutrophils of bipolar patients either unmedicated or
      treated with lithium salts or valproate and in neutrophils of unmedicated,
      matched healthy controls using quantitative real-time PCR. The content of SMIT
      mRNA was significantly reduced in neutrophils of lithium-treated bipolar patients
      compared to controls and to untreated bipolar patients. Untreated bipolar I
      patients but not bipolar II patients exhibited a significantly higher expression
      of SMIT mRNA than controls. Neutrophils of bipolar I patients treated with
      valproate exhibited a significantly lower expression of SMIT mRNA than untreated
      bipolar I patients but did not differ from controls. These results suggest that
      lithium and valproate down-regulate SMIT mRNA in vivo in patients. In addition
      the data provide first evidence that up-regulation of SMIT might be associated
      with an increased risk for bipolar I disorder.

PMID- 16420719
TI  - Predictors of survival in nursing home patients with severe dementia in whom
      artificial nutrition and hydration are [corrected] forgone.
AB  - BACKGROUND: To investigate the characteristics of patients in whom artificial
      nutrition and hydration (ANH) is forgone, duration of survival after the decision
      and factors that are associated with duration of survival. METHODS: Observational
      study based on written questionnaires in 32 Dutch nursing homes. Of 178 nursing
      home patients with dementia, their treating nursing home physician (NHP) filled
      in a questionnaire directly after the decision was made to forgo ANH. The maximum
      follow-up was 6 weeks. Cox proportional hazards analysis was used to determine
      predictors of survival. RESULTS: Decisions to forgo ANH in Dutch nursing homes
      were made most often in patients with severe dementia who also had an acute
      illness. More than half the patients (59%) died within 1 week after the decision.
      Patients with dyspnea and/or apathy were more likely to die during follow-up than
      patients without these symptoms. Patients who were considered more severely ill
      by the NHP were more likely to die than those who were considered less severely
      ill. The presence of restlessness indicated a higher chance of survival.
      CONCLUSIONS: The clinical judgment of the NHP of the severity of illness appeared
      to be a strong predictor of patient survival. NHPs should not rely solely on
      their clinical judgment concerning survival, but they should also consider the
      presence or absence of dyspnea, apathy and restlessness.

PMID- 16420718
TI  - Genetic complexity and gametocyte production of Plasmodium falciparum in Fulani
      and Mossi communities in Burkina Faso.
AB  - We have examined Plasmodium falciparum gametocyte prevalence, density and their
      genetic complexity among children of 2 sympatric ethnic groups (Mossi and Fulani)
      in villages in Burkina Faso. The 2 groups are known to have distinct differences
      in their susceptibility and immune responses to malaria. We used RT-PCR and
      sequence-specific probes to detect and type RNA of the gametocyte-specific
      protein Pfs48/45. There were no differences in detection rates of asexual forms
      and gametocytes among the 2 groups, using PCR and RT-PCR, respectively. However,
      there were significant differences in densities of asexual forms and gametocytes,
      which were both higher among Mossi than Fulani. Both asexual forms and gametocyte
      densities were influenced by age and ethnicity. Multiple-clone infections with
      more than 1 gametocyte genotype were equally prevalent among Fulani and Mossi.
      These differences can most probably be attributed to genetic differences in
      malaria susceptibility in the 2 ethnic groups.

PMID- 16420720
TI  - Late-onset obsessive-compulsive disorder: the role of stressful life events.
AB  - The onset of obsessive-compulsive disorder (OCD) for the first time in old age is
      uncommon and has been mostly related to cerebral abnormalities. We report a case
      of late-onset OCD in a 77-year-old woman following stressful life events but with
      a normal cerebral structure. The contribution of life events and vulnerability
      factors on the genesis and the presentation of her illness are discussed in
      relation to the literature on OCD.

PMID- 16420721
TI  - Practical application of family and systems theory in old age psychiatry: three
      case reports.
AB  - The role of the family or carer in old age psychiatry is well acknowledged.
      However, carer interventions are often focused on addressing carer burden alone
      and are usually individually rather than family based. Interpersonal conflict and
      family dynamics are rarely addressed. This is not surprising as there is a
      paucity of literature in family and systems theory applied to the older person,
      and clinicians are often skeptical about the efficacy of this treatment mode or
      daunted by the complexity of family and systems theory. Three cases are presented
      to illustrate the potential benefits of family-based interventions in the setting
      of commonly encountered clinical situations: (i) the treatment of chronically
      depressed older people in the community; (ii) the management of behavioral and
      psychological symptoms of dementia (BPSD) in residential care; and (iii) home
      based support and care of the older patient with dementia.

PMID- 16420722
TI  - Geriatric psychiatry consultations in a Turkish university hospital.
AB  - OBJECTIVE: The size of the elderly population is growing rapidly in Turkey. We
      aimed to characterize geriatric psychiatry consultations to obtain the
      characteristic pattern of these patients for further interventions. METHOD: A
      retrospective chart review was undertaken for each patient. RESULTS: One hundred
      and sixty-six patients with a mean age (+/- S.D.) of 75.5 +/- 6.6 years were
      included in this study. Most referrals came from the Department of Internal
      Medicine (42.2%), with sleep problems (42.1%), depression (29.5%) and anxiety
      (28.3%) being the most common reasons for referral. Hypertension was the most
      frequent medical diagnosis (53.6%). The mean number +/- S.D.) of medications used
      by each patient was 4.4 +/- 2.0. The leading psychiatric diagnosis at the end of
      the assessment was adjustment disorder (31.3%). CONCLUSION: Turkish geriatric
      psychiatry consultation patients display similar characteristics to elderly
      patients from other western countries. The main difference comes from diagnosis
      of adjustment disorder, which may be related to hospital conditions and strong
      family ties in developing countries.

PMID- 16420724
TI  - Characterization of virulence factors in the newly described Salmonella enterica
      serotype Keurmassar emerging in Senegal (sub-Saharan Africa).
AB  - From 2000 to 2001, nine strains of Salmonella enterica belonging to the new
      serotype Keurmassar have been isolated from human and poultry samples at the
      Senegalese National Salmonella and Shigella Reference Laboratory at the Pasteur
      Institute, in Dakar. All strains carried virulence factors including Salmonella
      Pathogenicity Islands (SPI)-1, -2, -3 and -5 encoded genes. Strains did not
      harbour virulence plasmid. Ribotyping analysis revealed a single clone identical
      to Salmonella Decatur isolated in Zimbabwe. These data suggest that strains are
      closely related, and may have been spread clonally. In this new serotype,
      insertion sequence IS200 is not present.

PMID- 16420723
TI  - Publication bias in foodborne outbreaks of infectious intestinal disease and its
      implications for evidence-based food policy. England and Wales 1992-2003.
AB  - Systematic national surveillance of outbreaks of infectious intestinal disease
      (IID) was introduced in England and Wales in 1992 to provide comprehensive
      information on causative organisms, sources or vehicles of infection and modes of
      transmission. We compared information from this system with that published in the
      peer-reviewed literature between 1 January 1992 and 31 January 2003 to assess the
      potential effect of publication bias on food-safety policy. During the study
      period 1763 foodborne outbreaks of IID were reported to national surveillance.
      Fifty-five were published in the peer-reviewed literature. The peer-reviewed
      literature overestimated the impacts of milk/milk products, miscellaneous foods
      (e.g. sandwiches) and desserts and underestimated those of poultry, fish and
      shellfish, red meat/meat products and eggs/egg products. Without systematic
      surveillance, knowledge of causative organisms, sources or vehicles of infection
      and modes of transmission, as gleaned from the peer-reviewed literature, would
      potentially distort food-safety policy.

PMID- 16420725
TI  - An outbreak of human salmonellosis caused by ampicillin-resistant Salmonella
      enterica serovar Enteritidis PT13 in the Czech Republic.
AB  - In summer 2004, an outbreak caused by Salmonella enterica serovar Enteritidis
      phage type 13 (S. Enteritidis PT13) was recorded in the Czech Republic. As well
      being a relatively rare phage type the strain was also ampicillin resistant.
      Outbreak (n=39) and pre-outbreak isolates (n=13) were characterized by pulsed
      field gel electrophoresis (PFGE), beta-lactamase gene polymerase chain reaction
      and plasmid profile. The majority of outbreak isolates (n=37) were identical in
      XbaI PFGE profile, and two other outbreak isolates each differed from this
      profile by one or two fragments respectively. The pre-outbreak isolates were
      uniform in PFGE profile but distinct from the outbreak strain. Ampicillin
      resistance was confirmed to be encoded by the blaTEM gene located on the TnA
      transposon. This gene was readily transferable to a S. Enteritidis recipient
      strain and was associated with the transfer of a 200-kb plasmid. Our results
      indicate that all S. Enteritidis PT13 tested from 2004 belonged to a single
      outbreak strain which prior to 2004 had not been recognized in the Czech
      Republic.

PMID- 16420726
TI  - Effectiveness of different policies in preventing meningococcal disease clusters
      following a single case in day-care and pre-school settings in Europe.
AB  - National policies for chemoprophylaxis after single cases of meningococcal
      disease in day-care or nursery settings vary across Europe. We carried out a
      multi-national retrospective study to compare the effectiveness of different
      policies. Countries were divided into those recommending chemoprophylaxis only to
      close contacts (policy A, close) and those recommending chemoprophylaxis for all
      children in the same nursery (policy B, mass). Country-specific relative risk
      (RR) of a cluster was defined as the ratio of the number of clusters observed to
      the number of clusters expected by chance. In total, 37 clusters were identified
      between 1 January 1993 and 31 December 2002. After adjusting for marked
      heterogeneity in RR by country, the ratio of RR between countries suggested
      possible benefit from mass prophylaxis (RR ratio 3.8, 95% CI 0.7-22.0), although
      the difference was not statistically significant (P=0.22). The costs of this
      approach and the low risk of clustering need to be taken into account when
      deciding national policy.

PMID- 16420727
TI  - Suicidality in chronic pain: a review of the prevalence, risk factors and
      psychological links.
AB  - BACKGROUND: This paper reviews and integrates the growing literature concerning
      the prevalence of and risk factors for suicidality in chronic pain. METHOD: A
      series of systematic searches in MEDLINE and PsychINFO identified 12 relevant
      articles examining suicide, suicide attempts, and suicidal ideation in chronic
      pain. A selection of theoretical and empirical work identifying psychological
      processes that have been implicated in both the pain and suicide literature and
      which may be related to increased suicidality was also reviewed. RESULTS:
      Relative to controls, risk of death by suicide appeared to be at least doubled in
      chronic pain patients. The lifetime prevalence of suicide attempts was between 5%
      and 14% in individuals with chronic pain, with the prevalence of suicidal
      ideation being approximately 20%. Eight risk factors for suicidality in chronic
      pain were identified, including the type, intensity and duration of pain and
      sleep-onset insomnia co-occurring with pain, which appeared to be pain-specific.
      Helplessness and hopelessness about pain, the desire for escape from pain, pain
      catastrophizing and avoidance, and problem-solving deficits were highlighted as
      psychological processes relevant to the understanding of suicidality in chronic
      pain. CONCLUSIONS: Programmatic research is urgently required to investigate the
      role of both general and pain-specific risk factors for suicidality, to examine
      how the psychological processes mentioned above mediate or exacerbate
      suicidality, and to develop enhanced interventions for pain patients at risk.

PMID- 16420728
TI  - Comparative development of Echinococcus multilocularis in its definitive hosts.
AB  - The comparative development of Echinococcus multilocularis was studied in its
      definitive hosts, the fox, dog, cat and raccoon dog, beyond the pre-patent period
      to 90 days post-infection. All host species, apart from cats were susceptible to
      infection and capable of supporting substantial worm burdens. Although worms in
      cats matured and produced thick-shelled eggs, their overall development was
      retarded compared to that in other species in which the parasite matured rapidly
      producing large populations of gravid worms. E. multilocularis matured rapidly in
      foxes and raccoon dogs and this was sustained in raccoon dogs but not in foxes in
      which maturation of worms declined during the later stages of infection, in
      contrast to that in both raccoon dogs and dogs. These populations were sustained
      for longer in raccoon dogs and dogs compared to foxes. Cats would appear to have
      only a minor role in the maintenance of E. multilocularis in endemic areas, and
      infections in cats may be of minimal public health significance. In contrast,
      foxes, dogs and the recently recognized definitive host the raccoon dog, are all
      capable of playing significant roles in the epidemiology of alveolar
      echinococcosis. This study also demonstrated that the developmental processes of
      growth, segmentation, proglottization and maturation in adult Echinococcus are
      independent and can be influenced by environmental factors thus confirming
      earlier in vitro observations.

PMID- 16420729
TI  - Impaired cognition and decision-making in bipolar depression but no 'affective
      bias' evident.
AB  - BACKGROUND: Depression is usually the predominant affective state in bipolar
      disorder. There are few studies, with discrepant views, examining the extent of
      cognitive impairment in patients with bipolar depression. To our knowledge, there
      are no previous studies examining decision-making ability or whether there is an
      affective attentional bias in bipolar depression. METHOD: We ascertained 24
      depressed bipolar I patients from acute psychiatric hospital wards and out
      patient clinics and 26 age- and IQ-matched healthy controls. Using computerized
      tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks
      (i.e. memory, attention and executive function) and on novel tasks of emotional
      cognition (i.e. the decision-making task and the affective go/no-go task).
      RESULTS: Accuracy measures were significantly impaired on tests of visual and
      spatial recognition and attentional set-shifting in bipolar depression compared
      with age- and IQ-matched controls. The quality of decision-making was also
      significantly impaired in the patients. A mood-congruent attentional bias for
      'sad' targets was not evident on the affective go/no-go task. CONCLUSIONS: We
      found widespread evidence of significant cognitive impairment and impaired
      quality of decision-making in symptomatically severe depressed bipolar patients.
      This cognitive impairment may contribute to difficulties with daily living,
      decision-making and the ability to engage and comply with psychological and drug
      treatments.

PMID- 16420732
TI  - Unsupervised pattern recognition: an introduction to the whys and wherefores of
      clustering microarray data.
AB  - Clustering has become an integral part of microarray data analysis and
      interpretation. The algorithmic basis of clustering -- the application of
      unsupervised machine-learning techniques to identify the patterns inherent in a
      data set -- is well established. This review discusses the biological motivations
      for and applications of these techniques to integrating gene expression data with
      other biological information, such as functional annotation, promoter data and
      proteomic data.

PMID- 16420731
TI  - A Bayesian method for analysing spotted microarray data.
AB  - In the decade since their invention, spotted microarrays have been undergoing
      technical advances that have increased the utility, scope and precision of their
      ability to measure gene expression. At the same time, more researchers are taking
      advantage of the fundamentally quantitative nature of these tools with refined
      experimental designs and sophisticated statistical analyses. These new approaches
      utilise the power of microarrays to estimate differences in gene expression
      levels, rather than just categorising genes as up- or down-regulated, and allow
      the comparison of expression data across multiple samples. In this review, some
      of the technical aspects of spotted microarrays that can affect statistical
      inference are highlighted, and a discussion is provided of how several methods
      for estimating gene expression level across multiple samples deal with these
      challenges. The focus is on a Bayesian analysis method, BAGEL, which is easy to
      implement and produces easily interpreted results.

PMID- 16420733
TI  - Evaluation of biomedical text-mining systems: lessons learned from information
      retrieval.
AB  - Biomedical text-mining systems have great promise for improving the efficiency
      and productivity of biomedical researchers. However, such systems are still not
      in routine use. One impediment to their development is the lack of systematic and
      rigorous evaluation, comparable to the approaches developed for information
      retrieval systems. The developers of text-mining systems need to improve both
      test collections for system-oriented evaluation and undertake user-oriented
      evaluations to determine the most effective use of their systems for their
      intended audience.

PMID- 16420734
TI  - What makes a gene name? Named entity recognition in the biomedical literature.
AB  - The recognition of biomedical concepts in natural text (named entity recognition,
      NER) is a key technology for automatic or semi-automatic analysis of textual
      resources. Precise NER tools are a prerequisite for many applications working on
      text, such as information retrieval, information extraction or document
      classification. Over the past years, the problem has achieved considerable
      attention in the bioinformatics community and experience has shown that NER in
      the life sciences is a rather difficult problem. Several systems and algorithms
      have been devised and implemented. In this paper, the problems and resources in
      NER research are described, the principal algorithms underlying most systems
      sketched, and the current state-of-the-art in the field surveyed.

PMID- 16420735
TI  - Software agents in molecular computational biology.
AB  - Progress made in applying agent systems to molecular computational biology is
      reviewed and strategies by which to exploit agent technology to greater advantage
      are investigated. Communities of software agents could play an important role in
      helping genome scientists design reagents for future research. The advent of
      genome sequencing in cattle and swine increases the complexity of data analysis
      required to conduct research in livestock genomics. Databases are always
      expanding and semantic differences among data are common. Agent platforms have
      been developed to deal with generic issues such as agent communication, life
      cycle management and advertisement of services (white and yellow pages). This
      frees computational biologists from the drudgery of having to re-invent the wheel
      on these common chores, giving them more time to focus on biology and
      bioinformatics. Agent platforms that comply with the Foundation for Intelligent
      Physical Agents (FIPA) standards are able to interoperate. In other words, agents
      developed on different platforms can communicate and cooperate with one another
      if domain-specific higher-level communication protocol details are agreed upon
      between different agent developers. Many software agent platforms are peer-to
      peer, which means that even if some of the agents and data repositories are
      temporarily unavailable, a subset of the goals of the system can still be met.
      Past use of software agents in bioinformatics indicates that an agent approach
      should prove fruitful. Examination of current problems in bioinformatics
      indicates that existing agent platforms should be adaptable to novel situations.

PMID- 16420736
TI  - Inferring network interactions within a cell.
AB  - The continuing growth in high-throughput data acquisition has led to a
      proliferation of network models to represent and analyse biological systems.
      These networks involve distinct interaction types detected by a combination of
      methods, ranging from directly observed physical interactions based in
      biochemistry to interactions inferred from phenotype measurements, genomic
      expression and comparative genomics. The discovery of interactions increasingly
      requires a blend of experimental and computational methods. Considering yeast as
      a model system, recent analytical methods are reviewed here and specific aims are
      proposed to improve network interaction inference and facilitate predictive
      biological modelling.

PMID- 16420737
TI  - WinPop 2.5: software for representing population genetics phenomena.
AB  - The curriculum for genetics courses is shifting from a classical to a more
      molecular genetics focus, increasing the importance of subjects such as
      population genetics. Population genetics is a computational and statistical field
      that requires a good understanding of the nature of stochastic events. It is a
      difficult field for biology students with a limited mathematical background and
      there is a need for visualisation tools to facilitate understanding by the use of
      practical examples. WinPop provides students and researchers with a visual tool
      to allow the simulation and representation of population genetics phenomena.
      WinPop is a user-friendly software meant for use in population genetics courses
      and basic research. WinPop 2.5 contains six different modules that represent and
      simulate population genetics models. Genotype and allele frequencies are
      calculated under the different models: panmixia, genetic drift, assortative
      matings, selection, gene flow and mutation. The program's interface presents
      information in Cartesian graphics and isosceles triangular coordinate systems,
      allowing the user to save graphical and textual data output from the simulations.
      WinPop is developed in Visual Basic 6.0 and uses Windows 95 and higher. WinPop
      2.5 can be downloaded from http://www.genedrift.org/winpop.php.

PMID- 16420738
TI  - Detecting horizontal gene transfer with T-REX and RHOM programs.
AB  - As the Human Genome Project and other genome projects experience remarkable
      success and a flood of biological data is produced by means of high-throughout
      sequencing techniques, detection of horizontal gene transfer (HGT) becomes a
      promising field in bioinformatics. This review describes two freeware programs: T
      REX for MS Windows and RHOM for Linux. T-REX is a graphical user interface
      program that offers functions to reconstruct the HGT network among the donor and
      receptor hosts from the gene and species distance matrices. RHOM is a set of
      command-line driven programs used to detect HGT in genomes. While T-REX impresses
      with a user-friendly interface and drawing of the reticulation network, the
      strength of RHOM is an extensive statistical framework of genome and the
      graphical display of the estimated sequence position probabilities for the
      candidate horizontally transferred genes.

PMID- 16420739
TI  - Structural features and structural variability of the lipopolysaccharide of
      Yersinia pestis, the cause of plague.
AB  - Data on the structure and temperature-dependent variations of the
      lipopolysaccharide (LPS) of Yersinia pestis are summarized and compared with data
      of other enteric bacteria, including other Yersinia spp. A correlation between
      the LPS structure and properties of the LPS and bacterial cultures as well as the
      LPS biosynthesis control are briefly discussed.

PMID- 16420740
TI  - GM-CSF priming of human monocytes is dependent on ERK1/2 activation.
AB  - The ability to augment monocyte functions such as TNF-alpha-producing capacities
      confers a high immunostimulating potential to GM-CSF. In the present
      investigation, the mechanism of the GMCSF-mediated enhancement of monocyte
      cytokine production was analysed with regard to the involvement of intracellular
      signalling pathways. GM-CSF primes human monocytes dose- and time-dependently for
      enhanced LPS-stimulated TNF-alpha synthesis. Pre-incubation with 10 ng/ml GM-CSF
      for 6 h before LPS stimulation (10 ng/ml) caused a 3.4 +/- 1.9-fold increase in
      TNF-alpha release compared to unprimed controls. This was associated with
      increased phosphorylation of IkappaBalpha and elevated nuclear levels of the NF
      kappaB components p50 and p65 and NF-kappaB binding to DNA. LPS-induced AP-1
      binding to DNA was also enhanced in GM-CSF-pre-incubated cells. GMCSF treatment
      also caused a slight increase in TLR4 expression on monocytes while CD14
      expression remained unchanged. GM-CSF-priming was unaffected by inhibitors of p38
      MAPK (SB203580) and lipoxygenase (NDGA). In contrast, the broad-spectrum tyrosine
      kinase inhibitor genistein and the MEK-1 inhibitor (PD98059) abrogated GM-CSF
      priming of TNF-alpha release and activation of both NF-kappaB and AP-1. It is
      concluded that a tyrosine kinase of the GM-CSF-triggered ERK1/2 pathway augments
      the LPS-induced NF-kappaB and AP-1 activation.

PMID- 16420741
TI  - Liver argininosuccinate synthase binds to bacterial lipopolysaccharides and lipid
      A and inactivates their biological activities.
AB  - The liver is known to clear and detoxify circulating lipopolysaccharide (LPS). To
      characterize the molecules involved in this process in the liver, we attempted to
      purify mouse liver protein(s) that can interact with lipid A, a biologically
      active portion of LPS. By partially purifying the inactivating activity against a
      synthetic lipid A analog, we observed the enrichment of a 45-kDa protein in the
      active fractions. The internal amino acid sequences of the protein were identical
      with those of argininosuccinate synthase (EC 6.3.4.5). To examine whether
      argininosuccinate synthase can interact with lipid A, we purified the enzyme from
      mouse liver and found the co-elevation of the specific enzyme activity and
      specific lipid A-inactivating activity, indicating that argininosuccinate
      synthase is the major lipid A-interacting protein in liver. Argininosuccinate
      synthase also inhibited the biological activities (macrophage activation and
      Limulus test) of natural lipid A and rough-type LPS but not smooth-type LPS. The
      enzyme activity was inhibited by lipid A and rough-type LPS and also by smooth
      type LPS. Native gel electrophoresis of a mixture of argininosuccinate synthase
      and LPS and immunoprecipitation of a mixture of argininosuccinate synthase and
      [(3)H]-LPS with anti-argininosuccinate synthase antiserum showed that
      argininosuccinate synthase stably bound lipid A and LPS. These findings,
      together, indicate that argininosuccinate synthase can effectively bind LPS in
      the liver.

PMID- 16420742
TI  - Reduced toxicity of lipo-oligosaccharide from a phoP mutant of Neisseria
      meningitidis: an in vitro demonstration.
AB  - PhoP is part of a two-component regulatory system, which we have previously
      demonstrated in Neisseria meningitidis and shown to be an important regulator of
      virulence in an in vivo model. The phoP mutant clearly induced cross-species
      reactive antibodies and lacks the obvious toxic effects of the wild-type strain.
      In the current study, we demonstrate distinct differences between the wild-type
      and mutant strains in an in vitro model of toxicity. At concentrations likely to
      be present early in an infection, the mutant was more efficient at stimulating an
      inflammatory response than the wild-type. However, at the concentrations likely
      to be found at the site of a fulminant infection, the mutant showed significantly
      weaker ability to stimulate the release of pro-inflammatory cytokines and the
      production of reactive oxygen and nitrogen intermediates. SDS-PAGE analysis of
      the isolated LOS from the wild-type and mutant showed a difference in the level
      of expression of two major species of LOS, a finding which was supported by
      preliminary MALDI-TOF analysis. These results suggest that the altered toxicity
      of the mutant may be due to the increased expression of a conformationally
      altered LOS species, which shows less affinity and avidity for the cellular
      receptors responsible for the inflammatory response to endotoxin.

PMID- 16420743
TI  - Apoptosis induction in gastric mucous cells in vitro: lesser potency of
      Helicobacter pylori than Escherichia coli lipopolysaccharide, but positive
      interaction with ibuprofen.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) cause peptic ulcer disease, but
      whether they interact with Helicobacter pylori to promote damage is
      controversial. Moreover, the reported induction of apoptosis in gastric cells by
      H. pylori lipopolysaccharide (LPS) (10(-9) g/ml) contrasts with studies showing
      low immunological potency of this LPS. Therefore, the effects of LPS from H.
      pylori NCTC 11637 and Escherichia coli O111:B4 on apoptosis in a primary culture
      of guinea-pig gastric mucous cells were investigated in the presence and absence
      of the NSAID, ibuprofen. Cell loss was estimated by a crystal violet assay, and
      apoptosis determined from caspase activity and from condensation and
      fragmentation of nuclei. Exposure to E. coli LPS for 24 h caused cell loss and
      enhanced apoptotic activity at concentrations >or= 10(-9) g/ml, but similar
      effects were only obtained with H. pylori LPS at concentrations >or= 10(-6) g/ml.
      Although ibuprofen (250 microM) caused cell loss and apoptosis, addition of
      either E. coli or H. pylori LPSs further enhanced these effects. In conclusion,
      LPS and ibuprofen interact to enhance gastric cell loss and apoptosis. In such
      interactions, E. coli LPS is more potent than that of H. pylori. The low potency
      of H. pylori LPS may contribute to a chronic low-grade gastritis that can be
      enhanced by the use of NSAIDs.

PMID- 16420744
TI  - Pro-atherogenic properties of lipopolysaccharide from the periodontal pathogen
      Actinobacillus actinomycetemcomitans.
AB  - An association between cardiovascular and periodontal disease may be due to
      lipopolysaccharide (LPS)-promoted release of inflammatory mediators, adverse
      alterations of the lipoprotein profile, and an imbalance in cholesterol
      homeostasis. Since periodontopathogenic potential differs between serotypes of a
      major periodontal pathogen, Actinobacillus actinomycetemcomitans, we studied the
      pro-atherogenic properties of LPS preparations from serotypes b and d strains on
      macrophages (RAW 264.7). A. actinomycetemcomitans LPS preparations induced a time
      dependent release of tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta). LPS induced foam cell formation and cholesteryl ester
      accumulation from native low density lipoprotein in the following order: A.
      actinomycetemcomitans strains JP2 (serotype b) > Y4 (serotype b) > IDH781
      (serotype d). mRNA expression levels of scavenger receptor class B, type-I, and
      ATP-binding cassette transporter-1, receptors mediating cholesterol efflux from
      macrophages, were decreased by LPS preparations. The results suggest that the pro
      atherogenic potential of A. actinomycetemcomitans LPS may depend on the infecting
      strain and correlate with the periodontopathogenic potential of the pathogen.

PMID- 16420745
TI  - Editorial. Mouse models of infectious disease.

PMID- 16420746
TI  - Genetic analysis of innate resistance to mouse cytomegalovirus (MCMV).
AB  - Innate immunity is inherited and is, therefore, particularly susceptible to
      analysis by classical genetic methods. The 'phenotype first' approach has already
      revealed the principal receptors of the innate immune system as well as several
      essential signalling intermediates. It has recently emerged that innate
      resistance to mouse cytomegalovirus (MCMV) infection depends upon a large number
      of host genes with non-redundant functions; hence, random germline mutagenesis
      frequently causes susceptibility to this pathogen. Approximately one in 30
      pedigrees derived from N-ethyl-N-nitrosourea-mutagenised progenitors bears a
      recessive mutation that disrupts resistance to MCMV. Moreover, many of the genes
      required for resistance to MCMV will undoubtedly prove to have broad roles in
      immunity, creating resistance to many other microbes. The forward genetics
      approach offers an excellent opportunity to identify many of the key components
      of the innate immune system.

PMID- 16420747
TI  - Controlling malaria and African trypanosomiasis: the role of the mouse.
AB  - Malaria and trypanosomiasis are vector-borne protozoal diseases which
      disproportionately affect the poor. Both give rise to immense human suffering;
      malaria exerts its effect directly on human health, while trypanosomiasis causes
      damage largely though its effect on the health and productivity of the livestock
      on which so many poor people depend. These diseases both have multifaceted and
      poorly understood mechanisms of pathogenesis, combined with relatively complex
      life cycles characterised by multiple stages in both insect vector and mammalian
      host. In both cases, there is a dramatic effect of host genotype on disease
      progression. This effect is apparent in both the human and cattle hosts and among
      inbred mouse strains. This provides an opportunity to use the mouse to probe the
      mechanisms underlying resistance or susceptibility to pathology. The availability
      of high-density linkage maps, the genome sequence and transcriptomics tools has
      transformed the power of the mouse to illuminate such fundamental aspects of the
      host--parasite interaction.

PMID- 16420748
TI  - Assessing the genetic component of the susceptibility of mice to viral
      infections.
AB  - Laboratory mice often exhibit wide differences in susceptibility when infected
      experimentally with viruses. Based on such observations, experiments have been
      designed to investigate the determinism of these differences at the molecular
      level, and a few genes that play a major role in the innate mechanisms of defence
      of the species toward viral aggressions have been characterised. For example, the
      extraordinary resistance of SJL mice to experimental infections with hepatitis
      virus strain A59 is the consequence of a structural alteration of a cell adhesion
      molecule which normally binds to the spikes of the virus, allowing its entry into
      the cells. If the virus cannot bind to the molecule, or if the molecule is
      absent, epithelial cells of the intestine and liver are not infected and mice are
      resistant. In the same way, most--not to say all--laboratory strains of mice are
      susceptible to infections with orthomyxoviruses or flaviviruses because essential
      molecules, the synthesis of which is normally triggered by interferon, are
      defective in these mice. Wild mice, by contrast --probably because they are
      constantly exposed to natural infections--are resistant. Finally, some mouse
      strains resist experimental infections by the mouse cytomegalovirus 1 (MCMV-1)
      because, once infected, these mice synthesise a molecule at the surface of
      infected cells which allows immediate recognition and killing by natural killer
      (NK) cells. With the exuberant development of mouse genetics and the constant
      generation of new mutant alleles, it is likely that many more genes with an
      impact on the phenotype of resistance or susceptibility will be identified in the
      forthcoming years. These genes are probably numerous, however, and many of them
      presumably interact with each other and/or have additive effects. This might slow
      down progress in our understanding of the innate mechanism of defence.

PMID- 16420749
TI  - Susceptibility and resistance to pneumococcal disease in mice.
AB  - Although pneumococcus is a major pathogen of humans and, every year, the
      bacterium causes illness and death in millions of individuals, the genetic basis
      of susceptibility to the bacterium is unknown. Previous attempts to identify the
      gene explaining differing susceptibility to pneumococcal disease in humans have
      been without significant success. In order to develop new hypotheses that can be
      tested in humans, significant efforts have been made using mouse models of
      infection and disease. Indeed, the majority of the information so far obtained on
      pneumococcal disease in vivo has come from mouse studies. Mice differ in their
      response to pneumococcal disease, however, and the genetic basis of
      susceptibility to infection is unknown. This review summarises the current
      knowledge of mouse susceptibility and resistance to pneumococcal infection.

PMID- 16420751
TI  - Listeria monocytogenes as a probe of immune function.
AB  - For almost half a century, the mouse model of Listeria monocytogenes infection
      has been used to analyse both innate and adaptive components of immunity and to
      discover key immune genes. Vast accumulated knowledge about the disease in mice
      provides a unique framework for identifying and characterising immune molecules
      using a variety of experimental approaches. To illustrate the range of questions
      that can be addressed using modern genetics and genomics tools, the authors
      provide an overview of the analysis of components of immune signalling networks
      using the mouse model of L. monocytogenes infection.

PMID- 16420750
TI  - Genetic regulation of host responses to group A streptococcus in mice.
AB  - The group A streptococci (GAS, Streptococcus pyogenes) are important human
      pathogens which can cause a variety of diseases, ranging from mild infections to
      very severe invasive diseases. In recent years, evidence has been accumulated
      that host genetic factors have a major influence on the outcome of streptococcal
      infections. Variability in the degree of susceptibility of different inbred mouse
      strains to infection with GAS has demonstrated that the host genetic background
      largely determines the susceptibility of mice to this pathogen. This information
      is particularly useful for studying the immune mechanisms underlying disease
      susceptibility in mice, and provides an entry point for the identification of
      host defence loci. This paper reviews the recent advances in the characterisation
      of pathogenic mechanisms associated with the development of GAS-induced septic
      shock in the mouse model and outlines the current knowledge regarding the genetic
      control of immune responses to Group A streptococcus in mice.

PMID- 16420752
TI  - Genetics of murine leishmaniasis.
AB  - Leishmaniasis encompasses a number of disease syndromes, caused by several
      species of the digenetic protozoan Leishmania, and is transmitted by sandflies.
      The mouse model of the disease has been used to identify genes involved in
      disease susceptibility--for example, the Slc11a1 gene, important in resistance to
      Leishmania donovani--and to map loci important in Leishmania major infection. The
      genetics of the host response to L. major has been shown to be complex and to
      involve much more than the T helper cell response.

PMID- 16420753
TI  - Mouse models for the genetic study of tuberculosis susceptibility.
AB  - Tuberculosis, mainly caused by the pathogenic bacterium Mycobacterium
      tuberculosis, remains an inestimable public health problem, despite the
      established use of the Bacillus Calmette-Guerin (BCG) vaccine, multidrug therapy
      and the existence of global tuberculosis control programmes. Statistics show that
      nearly 2 billion people (approximately one-third of the world's population) are
      infected with M. tuberculosis. For unknown reasons, only about 10 per cent of
      those infected by M. tuberculosis will develop tuberculosis, resulting in 9
      million new cases yearly and 2 million deaths. A better understanding of the host
      -mycobacterial--environmental interplay is central to developing better
      antituberculosis vaccines and treatments. This review will discuss how a clearer
      idea of this interplay is emerging with new genomic strategies in mouse models.

PMID- 16420754
TI  - [Hepatitis C--progress and challenge].

PMID- 16420755
TI  - [Retreatment with interferon of relapsed chronic hepatitis C patients].
AB  - OBJECTIVE: To evaluate the efficacy and investigate the influencing factors of
      the interferon (IFN) retreatment for patients with chronic hepatitis C relapsed
      after a previous IFN treatment. METHODS: A retrospective study was designed to
      analyze the retreatment with IFN of 60 relapsed chronic hepatitis C patients. All
      patients were from a randomized, opened and multi-center clinical trial about the
      efficacy and security of PEG-IFNalpha-2a compared to CIFNalpha-2a in the
      treatment of chronic hepatitis C in China. There were 35 patients treated with
      PEG-IFNalpha-2a and 25 with CIFNalpha-2a. The main parameter to evaluate the
      efficacy was sustained viral response (SVR) rate. The influence of viral
      concentration in serum, genotype and drug categories on the responses to IFN were
      analyzed. RESULTS: For all the patients, the end of treatment virus response
      (ETVR) and SVR rates were 55.00% and 35.00% respectively. ETVR rate of PEG
      IFNalpha-2a was significantly higher than that of CIFNalpha-2a (74.29% and 28.00%
      respectively, P < 0.01). SVR rate of PEG-IFNalpha-2a was also markedly higher
      than that of CIFNalpha-2a (45.71% and 20.00% respectively, P < 0.05). However,
      there was no significant difference between the high and low viral load groups.
      Among the patients with genotype 1, ETVR and SVR rates of PEG-IFNalpha-2a
      (75.00%, 45.83%) were significantly higher than those of CIFNalpha-2a (22.22%,
      11.11%), (P < 0.01, P < 0.05 respectively), but in patients with genotype non-1,
      there were no such differences between the two groups. CONCLUSION: Some relapsed
      patients were not responsive to the IFN retreatment. The efficacy of PEG-IFNalpha
      2a was superior to CIFNalpha-2a. The conventional IFN was not suggested to be
      used in the relapsed cases with genotype 1. The viral load was not associated
      with the efficacy of IFN retreatment.

PMID- 16420756
TI  - [The direct antiviral effect of interferon-gamma on hepatitis C virus replicon].
AB  - OBJECTIVE: To study the effects of interferon-gamma and interferon-gamma combined
      with interferon-alpha on HCV RNA replication and the possible mediators of
      interferon-gamma anti-HCV in vitro. METHODS: An HCV replicon cell culture system
      was established and the cells were treated with interferon-gamma or interferon
      gamma combined with interferon-alpha. HCV RNA levels in the cells were evaluated
      by semi-quantitative RT-PCR and real-time PCR, and the levels of NS5A protein
      were examined by Western blot. RESULTS: Interferon-gamma could inhibit HCV RNA
      replication and NS5A protein expression effectively; The anti-HCV effects of
      interferon-gamma were both in time-dependent and does-dependent manners;
      Pretreating the cells with interferon-gamma could significantly enhance the
      antiviral effects of interferon-alpha; The expressions of IRF-1, 2'5'-OAS1(p46),
      2'5'-OAS2(p69), ISGF3gamma and STAT1 were significantly increased after
      interferon-gamma treatment. CONCLUSION: Interferon-gamma has a direct inhibitory
      effect on HCV replicon RNA replication and NS5A expression, and both are in a
      dose and time dependent manner; Interferon-gamma has a synergistic anti-HCV
      effect with interferon-alpha. IRF-1, 2'5'-OAS1(p46), 2'5'-OAS2(p69) and
      ISGF3gamma may mediate the anti-HCV effects of interferon-gamma.

PMID- 16420757
TI  - [Inhibition of HCV replication by HCV specific U1 small nuclear RNA chimeric
      ribozyme in vivo].
AB  - OBJECTIVE: To determine the advantage of U1 small nuclear RNA as a ribozyme
      vector (U1-Rz) to inhibit HCV replication in vivo. METHODS: The 3rd stem-loop was
      substituted by HCV core specific ribozyme to construct an U1-Rz eucaryotic
      expression plasmid. Then it was co-transfected with pCMV/T7-NCRC Delta-luc into
      Huh7 cell line mediated by lipofectin. The cell lysis supernatant was subjected
      to Western blot and lumenometer to determine the luciferase levels. RESULTS: A U1
      snRNA chimeric ribozyme was constructed successfully. Both Rz and U1-Rz inhibited
      luciferase expression in Huh7 by 48.64% and 87.46%, respectively. CONCLUSION: Rz
      has more efficacy in cells when using U1 snRNA delivery system. U1 can be an
      efficient vector for HCV specific ribozyme.

PMID- 16420758
TI  - [Inhibition of hepatitis B virus replication and expression by RNA interference
      in vivo].
AB  - OBJECTIVE: To evaluate the inhibitory effect of small interfering RNA (siRNA)
      targeting HBV C gene region on hepatitis B virus (HBV) in vivo. METHODS: An
      animal model of HBV infection was developed hydrodynamically, and pcDNA3.1-HBV
      and siRNA were together injected into the tail vein of the BALB/c mice. HBsAg was
      analyzed by time-resolved immunofluorometric assay, HBV DNA was analyzed by
      fluorogenic quantitative PCR (FQ-PCR), HBV C-mRNA was detected by semi
      quantitative RT-PCR, and viral specific proteins (HBsAg and HBcAg) in the mice
      livers were assayed using immunohistochemical staining. RESULTS: In the mice, the
      siRNA effectively inhibited HBV replication and expression compared with the
      controls. The inhibitive effect of siRNA on HBV lasted at least 3 days.
      CONCLUSION: These results demonstrate that RNAi can substantially inhibit HBV
      replication and expression in vivo.

PMID- 16420759
TI  - [Study on quasispecies of hepatitis B virus and the clinical manifestation of
      their infection by melt curve analysis].
AB  - OBJECTIVES: To study the relationship between quasispecies of hepatitis B virus
      and the clinical manifestations of their infection, and to find the answer of why
      different quasispecies of HBV with the same genotype can induce different
      clinical situations. METHODS: Sixty serum samples, in all of which HBVs of
      genotype B exist, taken from 32 chronic asymptomatic carriers and 28 severe
      chronic hepatitis patients, were collected to detect quasispecies of HBV DNA by
      melt curve approach. Then the relationship between quasispecies of HBV of the
      same genotype and the clinical situation of their infection was studied by
      comparing the wave crests of the two sample groups. RESULTS: The data of the 60
      serum samples of HBV of genotype B detected by melt curve showed that HBV DNA in
      severe chronic hepatitis patients had more wave crests than that in chronic
      asymptomatic carriers (P < 0.05), suggesting that HBV in severe chronic hepatitis
      patients had more quasispecies than in the chronic asymptomatic carriers.
      CONCLUSION: The numbers of quasispecies of HBV correlate with the clinical
      situations of their infection. In the patients infected by HBV of the same
      genotype, those who have more HBV quasispecies would have more severe clinical
      manifestations.

PMID- 16420760
TI  - [Analysis of T cell receptor BV dominant usage and CDR3 sequences during acute
      exacerbation in patients with chronic hepatitis B].
AB  - OBJECTIVES: To understand the role cellular immunology plays in the pathogenesis
      of chronic hepatitis B (CHB) through analysis of T cell receptor (TCR) beta chain
      variable region gene (BV) family dominant usage and beta chain complementarity
      determining region3 (CDR3) sequences of peripheral blood mononuclear cells of the
      patients. METHODS: TCR BV families were amplified by inverse polymerase chain
      reaction (RT-PCR), and the dominant usage of BV families and CDR3 repertoire were
      analyzed by immunoscope technology for 8 CHB patients during their acute
      exacerbations and for 4 healthy blood donors who served as controls. The
      clonality of the T cells suspected by immunoscope was further confirmed by CDR3
      sequencing. RESULTS: The TCR BV CDR3 repertoire of the 4 healthy blood donors
      showed a Gaussian distribution. In the 8 CHB patients, however, the clonal
      expansion of T cells showed different TCR BV families with each patient. The T
      cells of the clonal expansion shared different CDR3 sequences. CONCLUSION: The
      peripheral blood T cells of CHB patients during their acute exacerbation showed
      significantly a clonal expansion and their T cell clonal expansion may be
      stimulated by several HBV epitopes. These results indicate that cellular
      immunology is involved in the pathogenesis of the liver inflammation process of
      CHB.

PMID- 16420761
TI  - [Study of the quasispecies dynamics of serum hepatitis B virus in a patient with
      acute exacerbations of chronic hepatitis B].
AB  - OBJECTIVES: To investigate the quasispecies dynamics of hepatitis B virus (HBV)
      during the course of exacerbation and resolution of chronic hepatitis B in a
      patients. METHODS: Five serum samples were collected from a patient with two
      episodes of exacerbation and resolution of chronic hepatitis B. A method of PCR
      TA cloning-conformation sensitive gel electrophoresis (CSGE)-sequencing was
      performed to study the dynamic changes of HBV quasispecies in basal core promoter
      (BCP), precore and core regions of HBV genome. RESULTS: Quasispecies complexity
      was 10 and 12 at the points of exacerbations, and 14 and 17 at the points of
      resolutions (t = 3.133, P < 0.05). Ratio of dominant quasispecies in HBV
      population was high (42.4% and 51.5%) during exacerbations and low (30.3% and
      21.2%) during resolutions (t = 3.295, P < 0.05). All dominant quasispecies,
      except the one during the second resolution, carried core P5T, L60V, S155T, and
      precore G1896A mutations. CONCLUSION: The composition of HBV quasispecies changes
      due to the change of host immune status, and immune pressure might lead to the
      selection of immune escape mutants.

PMID- 16420763
TI  - [Transcription factor activity profile of human hepatocellular carcinoma cell
      lines with different metastatic potentials].
AB  - OBJECTIVES: To examine the activities of transcription factors (TFs) in human
      hepatocellular carcinoma (HCC) cell lines with different metastatic potentials,
      so as to identify the TFs associated with HCC metastasis. METHODS: Transcription
      factor activity profile of Hep3B, MHCC97L and MHCC97H, three HCC cell lines with
      different metastatic potentials, were examined using protein/DNA array.
      Electrophoretic mobility shift assays (EMSA) and Western blot were used to
      confirm the results obtained by protein/DNA array. RESULTS: From a total of 345
      screened TFs, 7 activity differential TFs were found, of which 5 showed increased
      activity, including p53, hypoxia inducible factor-1 alpha (HIF-1alpha), signal
      transducer and activator of transcription 3 (Stat3) and Sp1, and 2 showed
      decreased activity including Rb and Smad3. CONCLUSION: The abnormal functioning
      of transcription factors is closely associated with HCC metastasis. Our present
      findings could be of help in expanding our understanding of the mechanism of HCC
      metastasis and identify new predictive biomarkers and therapeutic targets.

PMID- 16420762
TI  - [A clinical study of abnormal bone metabolism in patients with HBV liver
      cirrhosis].
AB  - OBJECTIVE: To study the pathogenesis of abnormal bone metabolism in patients with
      HBV liver cirrhosis. METHODS: NM-300 signal-energy X-ray absorptiometry system
      was used to measure the bone mineral density (BMD) in 61 liver cirrhosis patients
      and 30 age-matched healthy controls. The serum levels of 1,25(OH)2D3, parathyroid
      hormone (PTH), calcitonin (CT), bone gamma-carboxyglutamic acid-containing
      protein (BGP), IL-1beta, IL-6, tumor necrosis factor (TNF)alpha and urine
      crosslaps were also detected in these patients. RESULTS: BMD in patients with HBV
      liver cirrhosis was lower than those of the controls. The serum levels of
      1,25(OH)2D3 and BGP in cirrhosis patients were lower than those in the controls,
      and they were much lower in the osteoporosis (OP) group than in the non
      osteoporosis (NOP) group. The PTH and CT were higher significantly in the
      patients than in the controls. The changes of serum 1,25(OH)2D3 and BGP were
      correlated with the changes of BMD. The serum levels of IL-1beta, IL-6, TNFalpha
      and urine crosslaps in cirrhosis patients were higher than those of the controls,
      and they were much higher in the OP group than in the NOP group. We also found
      that the serum levels of IL-1beta, IL-6, TNFalpha and urine crosslaps had a
      negative correlation with BMD. CONCLUSIONS: These data suggest that bone
      formation is weakened and bone resorption is increased in patients with HBV liver
      cirrhosis, 1,25(OH)2D3 plays an important role in abnormal bone formation.
      Elevation of serum IL-1beta, IL-6, TNFalpha can accelerate bone resorption and
      cause hepatic bone disease (HBD). Taking 1,25(OH)2D3 and reducing the level of IL
      1beta, IL-6, TNFalpha may be very important in preventing and treating HBD.

PMID- 16420764
TI  - [A study on vasculogenic mimicry in hepatocellular carcinoma].
AB  - OBJECTIVE: To explore if vasculogenic mimicry (VM) exists in hepatocellular
      carcinoma (HCC) and to explain the clinical significance of VM. METHODS: Ninety
      nine HCC resection specimens with complete clinical and prognostic data were
      collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS
      staining of the histological preparations were conducted to explore if VM exists
      in those HCC. RESULTS: 12.12% (12 specimens) of the 99 specimens exhibited
      evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson
      pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to
      Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated
      HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC
      (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed
      and the stages of the cancers, using the TNM (tumor, node, metastases)
      classification criteria, were analyzed. These parameters of the VM and non-VM
      groups were compared. The mean TNM stage of the VM group was not more advanced
      than that of the non-VM group. The hematogenous metastases ( lung, bone,
      peritoneum et al) between the 2 groups were compared, and in the VM group the
      hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier
      actuarial survival curves were used to compare the VM group (n = 12) with the non
      VM group (n = 87). Median survival time of the VM group was 9 months and that of
      the non-VM group was 31 months. The VM group had a lower survival rate than the
      non-VM group (P < 0.01). CONCLUSION: VM exists in HCC, and the higher invasive
      HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM
      group had a higher rate of hematogenous metastases, a lower survival rate, and a
      poorer prognosis.

PMID- 16420765
TI  - [Relationship between hepatic insulin resistance and the expression of genes
      involved in hepatic glucose output].
AB  - OBJECTIVE: To study the relationship between hepatic insulin resistance induced
      by high fat diet and the expression of genes involving hepatic glucose output.
      METHODS: Normal 8-week-old male SD rats were randomly divided into two groups,
      i.e, normal chow group (NC, n = 10) and high fat diet group (HF, n = 10). They
      were fed for 28 weeks. Body weight and fasting blood glucose (FBG) were measured.
      At the end of the experiment, the rats were sacrificed and their fasting insulin
      (INS) and triglycerides (TG) were measured. Hepatic insulin sensitivity was
      measured by tissue uptake of 3H-2-deoxyglucose and the content of hepatic
      glycogen was measured using the anthrone method. Gene expression was investigated
      by using the semi-quantitative RT-PCR method. RESULTS: As compared with NC group,
      CF group rats developed visceral obesity which was accompanied by higher plasma
      TG. FBG in CF group increased starting from the 18th week (NC 4.77+/-63 mmol/L vs
      HF 5.45+/-87 mmol/L, P < 0.05). The rate of uptake of 3H-2-deoxyglucose in livers
      decreased by 51% in the HF group. The content of hepatic glycogen increased by
      92.4% (P < 0.01). The level of phosphoenolpyruvate carboxykinase (PEPCK) and PGC
      1a mRNA increased by 41.5% and 30.8%, respectively (P < 0.05). CONCLUSION: A high
      fat diet induced expressions of PGC-1a and PEPCK. It suggests that
      gluconeogenesis may play a role in the increase of hepatic glucose output and
      FBG.

PMID- 16420767
TI  - [Health-related quality of life of chronic hepatitis C patients].

PMID- 16420766
TI  - [Upregulating expressions of hepatic lipopolysaccharide receptors in nonalcoholic
      steatohepatitic rats].
AB  - OBJECTIVE: The expression of hepatic lipopolysaccharide (LPS) receptors in a rat
      nonalcoholic steatohepatitis (NASH) model was studied in order to explore the
      pathogenesis of NASH. METHODS: Forty-five male SD rats were fed with a high fat
      diet. These rats were sacrificed after high fat feeding at 8, 12, 16, 24 weeks.
      Hepatic expressions of CD14 were observed by immunohistochemistry and expressions
      of TLR4 were detected by RT-PCR. Hepatic expressions and serum levels of TNFa
      were measured by RT-PCR and ELISA. Some rats fed with normal rat food served as
      controls. RESULTS: At the 8th week fatty livers appeared, and hepatic expressions
      of CD14 (25.9+/-1.9) and TLR4mRNA (1.75+/-0.81) were upregulated compared to
      those in the control group (25.9+/-1.9 vs 12.4+/-0.7, 1.75+/-0.81 vs 0.98+/-0.33,
      P < 0.01, t > 2.756 and P < 0.05, t > 2.045). The hepatic expressions of the two
      kinds of receptors increased with the appearance of NASH at week 12 (61.8+/-1.9
      and 1.88+/-0.72, P < 0.01, t > 2.756 and P < 0.05, t > 2.045), They reached to
      their peaks at week 16 (71.5+/-1.3 and 5.64+/-0.87, both P < 0.01 and t > 2.756),
      and decreased slightly at week 24 (67.7+/-6.6 and 4.98+/-0.72, both P < 0.01 and
      t > 2.756). Hepatic expressions and serum levels of TNFa also increased starting
      at week 8, and remained at that high level from week 8 to week 24. CONCLUSION:
      The hepatic expressions of CD14 and TLR4 were up-regulated gradually in the
      established rat NASH model. It may be one of the factors responsible for the
      increase of hepatic sensitivity to LPS injury of the NASH rats and may play an
      important role in the pathogenesis of NASH.

PMID- 16420768
TI  - [Clinical implications of heterogeneity of hepatitis C virus].

PMID- 16420769
TI  - [Establishing a fluorescence quantitative polymerase chain reaction for detection
      of HBV cccDNA in serum].

PMID- 16420770
TI  - [Effect of hyperglycemia on the progress of rat liver fibrosis induced by carbon
      tetrachloride].

PMID- 16420771
TI  - [Effects of sp600125 on proliferation and protein expression of bcl-2 and c-myc
      in hepatic stellate cells].

PMID- 16420772
TI  - [The effects of plasma from patients with chronic severe hepatitis and hepatic
      failure on the proliferation and metabolic function of the C3A cell line].

PMID- 16420773
TI  - [RNA interference targeting human telomerase reverse transcriptase induces HepG2
      cell apoptosis].

PMID- 16420774
TI  - [Effect of a Ruditapes philippinarum diet on the development of experimental
      fatty liver in rabbits].

PMID- 16420776
TI  - [Comment on the AASLD position paper: the management of acute liver failure].

PMID- 16420775
TI  - [Study on the effects of human augmenter of liver regeneration on laminin B1
      chain gene promoter].

PMID- 16420777
TI  - [Clinical and pathological features and surgical treatment of hepatocellular
      carcinoma with intra-bile duct invasion and obstruction].

PMID- 16420778
TI  - Complementary and alternative medicine for MS.
AB  - Neurologists are often uncertain how to view the many complementary and
      alternative medicine (CAM) approaches, used by their patients. This is an
      important issue, as studies show that 50-75% of MS patients use one or more CAM
      therapies, and see CAM therapists more than conventional physicians. Moreover,
      many MS patients do not tell their physicians what they are doing, especially if
      they feel the physician will be judgmental.

PMID- 16420779
TI  - A review of the evidence for efficacy of complementary and alternative medicines
      in MS.
AB  - The role of complementary and alternative medicine for the management of MS
      symptoms lies in palliative care: this is borne out by the popularity of such
      therapies among people with MS. This article describes some of the major
      complementary and alternative therapies used to treat MS symptoms and whether
      their use is supported by evidence from randomized controlled trials. For the
      vast majority of complementary and alternative regimens researched, there are
      only one or two trials per therapy. Thus, it is difficult to recommend any
      specific modality. Several trials have investigated linoleic acid and its
      derivatives, magnetic field therapy and cannabis extracts. All three approaches
      appear to be of use in ameliorating MS symptoms but more research is needed.
      Other issues that should be considered by MS patients when taking a complementary
      or alternative therapy are discussed.

PMID- 16420780
TI  - MS treatment optimization: report from the 21st ETRIMS/10th ACTRIMS Congress, 28
      September-1 October 2005, Thessaloniki, Greece.
AB  - Around 3500 international delegates were presented with a broad scientific
      programme at the joint meeting of the 21st ECTRIMS and 10th ACTRIMS congress held
      last September. The meeting focused on the heterogeneity of MS and optimizing MS
      treatment--from the earliest stages to the long-term management of this chronic
      disease--with the goal of improving patient outcome.

PMID- 16420781
TI  - Health economic issues in MS.
AB  - The objectives of MS treatment are to avoid temporary disability due to relapses
      and to delay progression to permanent disability. There have been intense debates
      about whether new and costly MS treatments represent efficient use of resources,
      and which patients should be treated. Cost-effectiveness analysis attempts to
      estimate the trade-offs involved and to provide information that will assist the
      decision-making process. In chronic-progressive diseases, health gains and
      potential associated economic benefits are often most evident in the long term.
      Consequently, the potential impact of new treatments must be estimated, using
      models that project available knowledge into the future. These models can also
      explore scenarios that provide best value for money (e.g. by defining subgroups
      or criteria when treatment should be stopped). The different findings obtained by
      various cost-effectiveness studies of new MS treatments can be explained by the
      variations in methodological approaches, patient definitions and datasets used.
      The key is to communicate such differences transparently.

PMID- 16420782
TI  - Fabry's disease as a differential diagnosis of MS.
AB  - Fabry's disease is a genetically inherited error of glycosphingolipid metabolism
      that results from the defective activity of the lysosomal enzyme alpha
      galactosidase A (alpha-GalA). The enzymatic defect, caused by an X-linked
      recessive genes, leads to progressive deposition of neutral glycosphingolipids
      (predominantly globotriaosylceramide), with terminal alpha-galactosyl moieties,
      in most visceral tissues and fluids of the body. Cerebrovascular manifestations
      result from multifocal small-vessel involvement and may include thromboses,
      basilar arterial ischaemia and aneurysm, seizures, paroxystic hemiplegia or
      hemianaesthesia, vestibular disorders and frank cerebral haemorrhage. Severe
      neurological signs may be present without evidence of major thrombosis and are
      presumably due to multifocal small-vessel occlusive disease. Vascular ischaemia
      and lipid deposition in peripheral nerves may cause conduction abnormalities
      (slowed conduction velocities and distal latency). Sensory neurons in spinal
      ganglia and small myelinated and unmyelinated fibers are affected preferentially.

PMID- 16420783
TI  - [Subspecialization and quality of care in liver resections].

PMID- 16420784
TI  - [Antiangiogenic treatment of cancer].
AB  - The process of formation of new vessels from pre-existing capillaries is called
      angiogenesis. Angiogenesis is a complex process which involves distinct cells,
      soluble components and factors related to the extra-cellular matrix and which is
      highly important in a large variety of physiological and pathological processes
      in the body. Angiogenesis regulation takes place through a perfect equilibrium
      between the production and release of different stimulatory and inhibitory
      factors which vary in relation to needs and tissue types. A large number of
      diseases are characterized by alterations in the angiogenic process, either by an
      insufficiency or by excessive angiogenesis. The requirement of blood vessel
      proliferation for tumor growth was observed more than a century ago. Angiogenic
      treatment would have an indirect antitumoral action, inhibiting tumor
      vascularization and impairing the supply of essential nutrients for tumoral
      growth and development.

PMID- 16420785
TI  - [Conservative oncoplastic surgery in breast cancer. Indications and limitations
      to its application].
AB  - Conservative surgery is the technique of choice in the surgical treatment of
      women with breast cancer. The conflict between the extent of resection and the
      final cosmetic result can lead to asymmetries and deformities that are
      intensified after adjuvant treatment. The introduction of oncoplastic techniques
      in the conservative management of breast cancer have allowed the indication for
      breast conservation to be increased and have improved cosmetic results,
      increasing the technical alternatives available to general surgeons specialized
      in breast cancer. The present article aims to review the indications and
      limitations of these conservative oncoplastic techniques in the surgical
      management of women with breast cancer.

PMID- 16420786
TI  - [Toward zero mortality in liver resection. Presentation of 200 consecutive
      cases].
AB  - INTRODUCTION: Liver resection (LR) morbidity and mortality rates have dropped in
      recent decades. Mortality is now below 5% and morbidity is less than 30%. Our
      objective was to present a series of 200 LRs without mortality and to analyze the
      factors that may be related to complications. PATIENTS AND METHOD: Between
      January 1996 and October 2003, 200 LRs were performed in 177 patients. The most
      common indication was liver metastases in 123 patients (61.5%), primary malignant
      liver tumors in 27 patients (13.5%), bile duct tumors in 27 patients (13.5%) and
      benign disease in 23 patients (11.5%). Fifty-one percent of the resections were
      performed under hemihepatic vascular control and 49% were resections of central
      segments, segmentary and atypical resections. We studied the association between
      morbidity and age, sex, previous comorbidity, liver status, indication for
      surgery, number of resections, major and minor resections, resection extended to
      other organs, type of vascular occlusion, transfusion requirements, operating
      time, length of hospital stay and experience of the surgical team. RESULTS: There
      was no postoperative mortality. The morbidity rate was 17.5% (35 patients) and
      the most common complications were biliary (8%). Morbidity was related to
      transfusion (transfused patients presented more complications) (P < .001).
      Transfusion was greater in major resections, the first 100 resections and
      prolonged operations. Among the segmentary resections the Pringle maneuver
      reduced transfusion requirements but this difference was not statistically
      significant. Morbidity decreased in the second 100 resections, without
      significant differences. CONCLUSION: LRs can be performed with low mortality and
      morbidity. Biliary complications and blood transfusion should be avoided whenever
      possible.

PMID- 16420787
TI  - [Open versus laparoscopic resection in non-complicated colon cancer. A systematic
      review].
AB  - INTRODUCTION: The objective of this study was to determine the best surgical
      option for elective surgery in non-complicated colon cancer by comparing open
      (OR) and laparoscopic resection (LR). PATIENTS AND METHOD: A systematic review of
      the literature was performed. Studies of non-complicated colon cancer in adults
      treated by OS and LS published between 1990 and 2002 were analyzed. The MEDLINE,
      LILACS and COCHRANE databases were used, employing MeSH terms and free words.
      Selected studies were analyzed using a specially designed score of methodological
      quality to examine and compare studies with different types of design. The number
      of treated patients, 3-year actuarial survival rate, 3-year disease-free
      survival, recurrence, morbidity, mortality and the methodological quality of
      primary studies were analyzed. Means, medians, extreme values and weighted means
      were calculated, and the methodological quality of primary studies was compared
      using median 95% confidence intervals. RESULTS: Six hundred eighty related
      articles were found; of these, 11 were analyzed. Hospital stay was 10.1 days for
      OR and 6.5 days for LR. Morbidity was 19.5% for OR and 26.9% for LR and mortality
      was 1.6% and 1.7% respectively. With mean follow-up periods of 58 months for OR
      and 30 months for LR, actuarial and free-disease survival rates were 74.3% and
      75.6% for OR and 87.0% and 89.5% for LR. The median score for methodological
      quality was 16 for OR and 18.5 for LR. CONCLUSIONS: The early and medium-term
      results of LR are similar to those observed in OR in patients with non
      complicated colon cancer.

PMID- 16420788
TI  - [Surgical treatment of recurrent secondary hyperparathyroidism].
AB  - INTRODUCTION: Secondary renal hyperparathyroidism (SHPT) affects nearly all
      patients on regular hemodialysis. Between 5% and 10% will need surgery to control
      the disease. Despite a meticulous technique, the rate of recurrent/persistent
      hyperparathyroidism after surgery remains between 2% and 12%. PATIENTS AND
      METHOD: We reviewed the reoperations of 7 patients with recurrent or persistent
      SHPT from a series of 56 patients, 3 of which were referred from other units for
      treatment of recurrence. Subtotal parathyroidectomy (ST-PTX) was performed in 51
      patients and total parathyroidectomy with autograft (TPTX-AT) was performed in
      the remaining 5 patients. RESULTS: Seven patients underwent reoperation for
      recurrent SHPT, 1 of them twice (8 reinterventions in 56 patients). In 2 patients
      only 3 parathyroid glands were removed at the first intervention and recurrence
      was due to the presence of a fourth gland. In 4 patients, ST-PTX was performed
      and recurrence was due to a remnant hyperplasic area in 1 and to a fifth gland in
      3. Recurrence in the patient with a TPTX-AT was to due to cervical
      parathyromatosis. All the patients with recurrence had a positive preoperative Tc
      MIBI scintigraphy and the computed tomography/magnetic resonance examination was
      highly useful for anatomical localization of the lesion and for planning the
      surgical approach.

PMID- 16420789
TI  - [Cyclooxygenase-2 expression as a prognostic factor in sporadic colorectal
      cancer].
AB  - INTRODUCTION: The aims of the present study were to investigate cyclooxygenase-2
      expression in neoplastic cells from colorectal carcinoma and to study the role of
      cyclooxygenase-2 expression as a prognostic factor related to distant metastases
      and survival. PATIENTS AND METHOD: A retrospective study of 105 patients with
      sporadic colorectal cancer was performed. The patients underwent surgery at the
      General Surgery Department of the University Hospital of Jaen between 1991 and
      1997. Several clinicopathological features were recorded: gender, tumor location,
      TNM stage, histological type and grade and the presence of venous or lymphatic
      invasion. The mean time of follow-up was 54 months. Immunohistochemistry:
      cyclooxygenase-2 expression was tested using avidin-biotin-peroxidase
      immunostaining. Both the intensity and extension of the stain were assessed.
      RESULTS: Cyclooxygenase-2 expression in neoplastic cells was considered to be
      positive in 38 cases (36.2%). No statistically significant relationship was found
      between cyclooxygenase-2 expression and the clinicopathological features recorded
      (P >.05). Tumor recurrence: Distant metastases were diagnosed in 14 patients
      (13.3%). Cyclooxygenase-2 did not show a significant relationship with metastases
      in the multivariate analysis (HR: 0.36; 95% confidence interval [CI]: 0.07-1.69).
      Survival: Mean survival time was 55 months. Multivariate analysis did not show
      cyclooxygenase-2 as an independent risk factor of death (HR: 0.51; 95% CI: 0.22
      1.21). CONCLUSIONS: Cyclooxygenase-2 expression was not significantly related to
      clinical and histopathological features of the tumors nor was it an independent
      risk factor of tumour recurrence or survival.

PMID- 16420790
TI  - [Inguinofemoral hernia: multicenter study of surgical techniques].
AB  - INTRODUCTION: The present study was performed by the Spanish Association of
      surgeons through its abdominal wall and sutures section. The aim was to determine
      the current situation of inguinofemoral hernias in Spain and was based on an
      anonymous multicenter study with the participation of various national hospitals.
      MATERIAL AND METHOD: Fifty general surgery departments in distinct surgical
      centers throughout Spain responded to an anonymous survey in 2000. The survey
      gathered data on anesthetic features, surgical techniques and complications in
      the treatment of inguinofemoral hernias. RESULTS: Sixty-six percent of hospital
      centers had a specific abdominal wall unit and 24% performed laparoscopic hernia
      surgery. Prosthetic techniques (especially Lichtenstein) were the most frequently
      used in the treatment of primary inguinal hernia (72%) and recurrent hernia
      (100%). The most frequently used prosthetic material was polypropylene mesh
      (76%). Only 28% of the departments surveyed performed anatomic techniques in the
      repair of primary inguinal hernia (Shouldice and Bassini). The most frequent
      treatment for femoral hernia was the Lichtenstein "plug" (78%). Sixty-eight
      percent of the centers surveyed performed regional anesthesia, 18% used general
      anesthesia and only 14% used local anesthesia with sedation. Severe complications
      were found in 20% of departments. Clinical postoperative follow-up was performed
      in 96% of the centers and telephone follow-up was used in 4%. The recurrence rate
      was 1.2% for primary inguinal hernia, 2.7% for recurrent inguinal hernia and 0.3%
      for femoral hernia. CONCLUSIONS: In Spain the most commonly used surgical
      technique in the treatment of inguinal hernia is Lichtenstein hernioplasty under
      spinal anesthesia and with polypropylene prosthesis. The Lichtenstein plug is the
      most commonly used technique in the treatment of femoral hernia.

PMID- 16420791
TI  - [Primary angiosarcoma of the spleen with liver metastases. Case report and
      literature review].
AB  - Angiosarcomas of the spleen are infrequent tumors that often present with liver
      metastases. These tumors are usually multiple and have a poor prognosis.
      Immunohistochemical markers can aid preoperative diagnosis since radiological and
      ultrasonographic images are fairly nonspecific. The recommended treatment is
      splenectomy. The benefits of chemotherapy and radiotherapy have not been clearly
      demonstrated.

PMID- 16420792
TI  - [Tracheal injury from cervical stabbing].
AB  - We report a case of isolated tracheal injury after a cervical stab without any
      other cervical damage. Diagnosis was performed by bronchoscopic and clinical
      examination. Plastic suture was performed with end-to-end anastomosis. The
      patient was discharged with good health status on the eleventh postoperative day.

PMID- 16420793
TI  - [Giant epidermoid splenic cyst].
AB  - Giant epidermoid splenic cysts are rare benign tumors. Their treatment is
      becoming increasingly less aggressive and more conservative. We report the case
      of a young woman with a giant epidermoid cyst, which required open total
      splenectomy, and review the literature on benign congenital tumors of the spleen.

PMID- 16420795
TI  - [Acute intestinal anisakiasis].

PMID- 16420794
TI  - [Gas gangrene].

PMID- 16420796
TI  - [Gastrointestinal bleeding and intestinal invagination due to intestinal
      choriocarcinoma].

PMID- 16420797
TI  - [Minimally-invasive esophagectomy].

PMID- 16420799
TI  - [Sentinel node detection in malignant melanoma. Importance of localization of the
      primary tumor].

PMID- 16420800
TI  - [Treatment of chronic anal fissure].
AB  - Chronic anal fissure is a common benign anorectal problem in Western countries
      that substantially impairs the patient's life. Consequently, a rapid and
      effective solution is required. We reviewed the various treatments for chronic
      anal fissure described in the literature, with the aim of establishing a
      therapeutic protocol. We recommend surgical sphincterotomy (preferably open or
      closed lateral sphincterotomy) as the first therapeutic approach in patients with
      chronic anal fissure. However, we prefer the use of chemical sphincterotomy
      (preferably botulinum toxin) in patients aged more than 50 years old and in those
      with previous incontinence, risk factors for incontinence (previous anal surgery,
      multiple vaginal births, diabetes, inflammatory bowel disease, etc.), or without
      anal hypertonia, despite the higher recurrence rate with medical treatments,
      since this procedure avoids the greater risk of residual incontinence described
      in the literature with surgical sphincterotomy in this group of patients.

PMID- 16420801
TI  - [Liver metastases from colorectal cancer. Is the practice of surgery based on the
      best clinical evidence possible?].
AB  - To date, surgical resection remains the only curative treatment for liver
      metastases from colorectal cancer. However, the evidence supporting this
      treatment is based on retrospective studies. The lack of level I clinical
      evidence has stimulated strong interest in identifying the factors predictive of
      recurrence, and even to use them to create clinical risk scores (assigning one
      point to each factor for poor prognosis), in which a higher score indicates a
      poorer prognosis. In the present review, we discuss all these factors, as well as
      the therapeutic alternatives that improve local disease control. Next, we review
      all the prospective randomized studies published on this topic, which mainly
      focus on adjuvant chemotherapy associated with curative surgery with negative
      margins, with the aim of validating or rejecting this treatment. Lastly, we
      include the algorithm of the University of California at San Francisco for
      surgery in liver metastases from colorectal cancer.

PMID- 16420802
TI  - [Anatomical location of the primary tumor as a variable to be considered in
      sentinel node biopsy of cutaneous melanoma].
AB  - INTRODUCTION: The anatomical location of cutaneous melanoma has been suggested to
      be an independent prognostic factor. The aim of the present study was to
      determine whether the location of the primary tumor influences sentinel node
      detection in cutaneous melanoma. PATIENTS AND METHOD: Two hundred twelve patients
      with primary cutaneous melanoma (96 of the limbs, 89 of the trunk and 27 of the
      head or neck) who underwent sentinel lymph node biopsy were studied. Adequate
      lymphoscintigraphic and surgical localization was evaluated and epidemiological
      and histopathological variables, the number of lymph nodes draining the site of
      the primary lesion, sentinel nodes per drainage basin, and tumor-positive nodes
      were compared. RESULTS: Localization was less successful for tumors of the head
      and neck (88.8%), both with lymphoscintigraphy (P<.001) and surgery (P<.0005),
      especially for lymph nodes adjacent to salivary glands (P<.0005). Melanomas of
      the trunk showed a greater number of nodes per lesion and wider variability in
      drainage pathways (P<.0005), although there were no differences in the number of
      sentinel nodes per drainage basin (P=.455). CONCLUSIONS: Sentinel node detection
      with less successful in cutaneous melanomas located in the head and neck.
      Location of the sentinel node adjacent to a salivary gland is a factor that
      influences its detection. Cutaneous melanomas of the trunk showed a higher number
      of draining nodes per lesion than those located in the limbs or head and neck.

PMID- 16420803
TI  - [The Hartmann procedure: current situation in Spain].
AB  - INTRODUCTION: The therapeutic alternatives in emergency surgery of the colon are
      a constant subject of debate and the Hartmann procedure is one of the most
      controversial techniques. The aim of the present study was to analyze when, why
      and in whom this procedure is performed, as well as its results. PATIENTS AND
      METHOD: We performed a descriptive analysis of 105 emergency Hartmann procedures.
      Clinical variables (age, sex, antecedents, symptoms, risk factors, preoperative
      diagnosis) were analyzed and correlated with surgical variables (surgical
      findings, surgeon) indicating the Hartmann procedure depending on general and
      local factors. RESULTS: The mean age was 69.3 years and 56% of the patients were
      men. Seventy-three percent had personal antecedents. Presenting symptoms were
      occlusion in 48%, acute abdomen in 30% and septic shock in 12%. Seventy-eight
      percent were ASA III-IV. The most frequent surgical findings were intestinal
      occlusion (39%), purulent peritonitis (22%) and fecal peritonitis (18%).
      Perforation of the colon was found in 14%. Morbidity was 51% and mortality was
      11%. Sixty-three percent of the procedures were performed by general surgeons and
      37% by specialists in colorectal surgery. In 20 patients intestinal continuity
      was restored after a mean wait of 9 months. Retrospective evaluation of the
      indications for the Hartmann procedure revealed that 50.5% of the patients could
      have undergone anastomosis and the reasons for not performing this procedure were
      analyzed. CONCLUSION: In our experience the Hartmann procedure is performed
      primarily for factors related to the patient (risk factors, general status and
      local status of the abdomen) and secondly due to factors related to the duty
      surgeon.

PMID- 16420804
TI  - [Is impact factor an appropriate index to determine the level of evidence of
      studies on therapeutic procedures in surgery journals?].
AB  - INTRODUCTION: The aim of this study was to determine the association between the
      IF of surgery journals and the level of evidence of articles on therapeutic
      procedures published in these journals. MATERIAL AND METHOD: A bibliometric study
      was performed. Journals listed in the 2002 ISI under the subject heading of
      Surgery were included. Journals were classified by applying the 33rd percentile
      of their IF (group 1 from 0.128 to 1.690, group 2 from 1.691 to 2.886, and group
      3 from 2.887 to 6.674). Simple randomized sampling was conducted of journals in
      each group (group 1: Eur J Surg, Am Surg and World J Surg; group 2: J Am Coll
      Surg, Surgery and Arch Surg; and group 3: Br J Surg and Ann Surg). A crossover
      analysis was performed by 2 independent teams of reviewers. RESULTS: There were
      751 article on therapy (41.2%). The mean IF was 1.66 +/- 0.48 for group 1, 2.61
      +/- 0.15 for group 2, and 4.69 +/- 1.57 for group 3 (P<.001). There were 16
      systematic reviews, 82 randomized clinical trials, 96 cohort studies, 474 case
      series and 79 review articles. Level 1 evidence was found in only 4.8% of the
      articles. Statistical differences were verified in 15.1% of the study sample,
      which was represented by systematic reviews and randomized clinical trials (most
      frequent in group 3 (P<.001). CONCLUSIONS: An association between the IF of
      scientific surgical journals and the level of evidence in articles published on
      therapy was verified.

PMID- 16420805
TI  - [Prophylaxis of sternal dehiscence in obese patients through systematic
      application of Robicsek closure].
AB  - INTRODUCTION: Sternal dehiscence is a relatively frequent complication in median
      sternotomy and causes high morbidity and mortality in cardiothoracic surgery.
      Obesity is one of the most important risk factors for sternal infection and
      dehiscence and its prevalence is increasingly frequent in patients undergoing
      cardiac surgery. The aim of the present study was to assess the clinical benefit
      of the prophylactic use of Robicsek sternal reinforcement in high-risk patients
      undergoing cardiac surgery. PATIENTS AND METHOD: Two hundred ninety consecutive
      patients who underwent median sternotomy in our center were analyzed. The
      indications for prophylactic sternal reinforcement were severe sternal
      osteoporosis or a body mass index (BMI) of > or = 30. The technique was used in
      105 patients, 54 men and 51 women, with a mean age of 67.7 +/- 9.1 years and a
      mean BMI of 31.8 +/- 4.1. RESULTS: None of the patients in the reinforcement
      group developed noninfectious dehiscence; only one patient (1.7%) in this group
      showed sternal dehiscence due to osteomyelitis with good response to surgical
      debridement and intravenous antibiotics. CONCLUSION: Robicsek reinforcement
      reduces the incidence of sternal dehiscence in high-risk patients and its
      prophylactic use should be considered in patients with severe osteoporosis or a
      BMI of > or = 30.

PMID- 16420806
TI  - [Use of a composite prosthesis (PL-PU99) versus a biological prosthesis
      (Surgisis) in an experimental model of temporary abdominal closure].
AB  - INTRODUCTION: In some diseases of peritoneal origin, temporary closure of the
      abdominal cavity is required to avoid compartmental syndrome. This allows normal
      intra-abdominal pressure to be maintained and the fascial edges to be preserved
      for subsequent definitive closure. MATERIAL AND METHOD: Defects (7 x 4 cm) were
      created in the anterior abdominal wall of New Zealand white rabbits and were
      repaired using an oval-shaped patch of a prosthesis designed by our team (PL
      PU99) or a prosthesis of biological origin (Surgisis) of similar dimensions to
      the defects. The biomaterials were fixed to the cut edges of the wall by 2
      polypropylene running sutures interrupted only at the corners, leaving the patch
      in contact with the atmosphere. Fourteen days after implantation,
      prosthesis/anchorage tissue specimens were taken for light and scanning electron
      microscopy, morphometric measurements and immunohistochemical macrophage
      identification (using the RAM-11 antibody). RESULTS: There were no cases of
      mortality or implant rejection. Small areas of loose adhesions were observed on
      some implants (covering 0.31 +/- 0.03% of the PL-PU99 implants and 31.60 +/-
      7.35% of Surgisis). The neoperitoneum induced by both implant types was
      homogenous and well organized, with thicknesses of 427.60 +/- 8.38 microm (PL
      PU99) and 171.99 +/- 18.70 microm (Surgisis). No significant differences were
      observed in terms of the macrophage reaction induced (PL-PU99 19.76 +/- 1.59%;
      Surgisis 21.07 +/- 8.93% macrophages). CONCLUSIONS: a) The PL-PU99 prosthesis
      provoked fewer adhesions and generated a thicker neoperitoneum. b) Both
      prostheses would probably be suitable for temporary closure of the abdominal
      cavity.

PMID- 16420807
TI  - [Exceptional iatrogenic ureteral rupture].
AB  - Rupture of the ureter is an infrequent event that can have serious consequences.
      The most frequent cause is surgical iatrogenic ureter disease. Other possible
      causes are urological procedures and urographic studies. In our patient, which,
      to our knowledge, is the first to be reported in the literature, the ureteral
      rupture was produced by a traumatic urinary catheterism, because the balloon was
      filled inside the ureter. The normal presentation is nephritic colic, although
      acute abdomen is also a possibility. The possibility of ureteral rupture in
      abdominopelvic surgery or in urological techniques should be evaluated when
      patients present these clinical symptoms. Treatment is surgical, although in some
      cases conservative measures can be used.

PMID- 16420808
TI  - [Idiopathic pneumoperitoneum].
AB  - We report the case of a 48-year-old man who was admitted to the intensive care
      unit for acute respiratory distress. After discharge, the patient showed massive
      pneumoperitoneum. None of the complementary investigations provided information
      on the cause. The patient underwent surgery but no intraoperative diagnosis was
      reached. We believe that this case is of interest since pneumoperitoneum is a
      frequent entity that often leads to emergency laparotomy. The cause is usually
      perforation, although in a substantial proportion of cases the pneumoperitoneum
      is non-surgical, or idiopathic.

PMID- 16420809
TI  - [Perforation of choledochal cyst in a 12-year-old boy].
AB  - Choledochal cyst is a rare congenital malformation that presents in children and
      young adults and is more frequent in women. Early diagnosis is essential to avoid
      possible complications. The method of choice for the initial diagnosis is
      ultrasound. Treatment consists of complete resection of the cyst. We describe a
      case of perforation of a choledochal cyst in a 12-year-old boy.

PMID- 16420810
TI  - [Infracecal cystic tumor].

PMID- 16420811
TI  - [Local recurrence 40 years after Halsted mastectomy].

PMID- 16420812
TI  - [Aneurysm of the superior mesenteric artery].

PMID- 16420813
TI  - [Translational research in surgery].

PMID- 16420814
TI  - [Robots in general surgery: present and future].
AB  - Robotic surgery is an emerging technology. We began to use this technique in
      2000, after it was approved by the Food and Drug Administration. Our preliminary
      experience was satisfactory. We report 4 years' experience of using this
      technique in our institution. Between August 2000 and December 2004, 399 patients
      underwent robotic surgery using the Da Vinci system. We performed 110 gastric
      bypass procedures, 30 Lap band, 59 Heller myotomies, 12 Nissen fundoplications, 6
      epiphrenic diverticula, 18 total esophagectomies, 3 esophageal leiomyoma
      resections, 1 pyloroplasty, 2 gastrojejunostomies, 2 transduodenal
      sphincteroplasties, 10 adrenalectomies and 145 living-related donor
      nephrectomies. Operating times for fundoplications and Lap band were longer.
      After the learning curve, the operating times and morbidity of the remaining
      procedures were considerably reduced. Robot-assisted surgery allows advanced
      laparoscopic procedures to be performed with enhanced results given that it
      reduces the learning curve as measured by operating time and morbidity.

PMID- 16420815
TI  - [Proposal for a new classification of prostheses used in the repair of abdominal
      wall hernial defects].
AB  - Research and development in new biomaterials is currently increasing. The greater
      use of prostheses for the repair of abdominal wall defects has meant that new
      designs incorporating novel materials are constantly emerging. Today's surgeon
      needs to be aware of these novel designs and become familiar with their use. In
      the present article, we classify the prostheses currently available on the market
      for the repair of abdominal wall defects, mostly hernias. The new classification
      scheme we propose takes into account the type of prosthesis, its components, and
      its ideal site of placement in the abdominal wall.

PMID- 16420816
TI  - [Initial results of the National Registry of Laparoscopic Liver Surgery].
AB  - INTRODUCTION: Experience in laparoscopic liver surgery is limited, and
      multicenter studies with large series are required for a critical evaluation of
      this type of surgery. OBJECTIVE: To analyze the results of the National Registry
      of Laparoscopic Liver Surgery. Indications, technical features, conversion rates,
      morbidity, and mortality were analyzed. PATIENTS AND METHOD: Seventy-four
      patients from 10 centers who underwent surgery between February 2000 and April
      2005 were included. There were 58 women and 16 men, with a mean age of 55 years.
      More than one lesion was present in 16 patients. Consequently, 74 patients with
      156 lesions were treated. RESULTS: Forty-six patients had cystic lesions (26
      simple cysts, 13 polycystic disease, five hydatid cysts and two cystic adenomas).
      Surgical treatment consisted of 37 fenestrations, five cystopericystectomies, two
      atypical resections, one segmentectomy and one bisegmentectomy of segments II
      III. In 28 patients the lesions were solid (four adenomas, six focal nodular
      hyperplasias, three hemangiomas, four hepatocarcinomas, five colorectal
      metastases, two lung metastases, one breast metastasis, one malignant melanoma
      metastasis, one pancreatic vipoma metastasis, and one lymphoma). Ten
      bisegmentectomies of segments II-III, 17 atypical resections and one
      segmentectomy of segment III were performed. Other surgery was associated in 23
      patients. The mean operating time was 160.5 minutes and the conversion rate was
      8%. The mean length of hospital stay was 5.6 days and was less than 5 days in 78%
      of the patients. Analgesia was administered for less than 48 hours in 55%.
      Morbidity was observed in eight patients (10.8%). Reoperations were performed in
      three patients. There was no mortality in this series. CONCLUSIONS: Laparoscopic
      hepatic resection is safe and feasible in selected patients. Large, controlled
      series are required to determine long-term outcomes. The national registry
      provides a good basis for evaluating laparoscopic liver surgery in Spain.

PMID- 16420817
TI  - [Liver transplantation in the management of unresectable bilateral neuroendocrine
      metastases].
AB  - INTRODUCTION: Neuroendocrine tumors are rare neoplasms that present bilateral
      liver metastases at diagnosis. Because of the good initial results obtained,
      liver transplantation is considered as a potentially curative treatment.
      OBJECTIVE: Present our experience of the use of liver transplantation in the
      management of unresectable bilateral neuroendocrine metastases. PATIENTS AND
      METHODS: We retrospectively reviewed the medical records of eight patients (four
      men and four women), with a mean age of 45 years, who underwent liver
      transplantation due to bilateral neuroendocrine liver metastases between January
      1996 and January 2005. The most frequent location of the primary tumor was the
      pancreas in five patients (one carcinoid, one gastrinoma and three non
      functioning tumors). The remaining three tumors were located in the small bowel
      (two) and in the lung. RESULTS: Only one patient died due to technical
      complications related to the transplant, representing a mortality rate for the
      entire group of 14%. After a median follow-up of 3 years (range: 1 month-6
      years), two patients died due to tumoral recurrence at 15 and 17 months,
      representing a tumoral recurrence rate of 33%. The survival rate at 1 and 3 years
      was 86% and 57%, respectively. CONCLUSIONS: Despite the initial promising results
      obtained with liver transplantation in the management of unresectable
      neuroendocrine liver metastases, our results indicate that careful patient
      selection is required. The key to obtaining good results is individualization of
      the indication for this procedure.

PMID- 16420818
TI  - [Intraoperative factors predictive of failure of the ambulatory regimen after
      laparoscopic cholecystectomy].
AB  - OBJECTIVES: To determine which intraoperative factors during ambulatory
      laparoscopic cholecystectomy predict postoperative admission. MATERIAL AND
      METHOD: Between January 1999 and August 2003, we attempted 410 consecutive
      laparoscopic cholecystectomies. Intraoperative variables were analyzed using
      univariate and multivariate methods. An intraoperative score was applied to
      determine the probability of successful ambulatory surgery in each patient.
      RESULTS: A total of 88.5% of the patients were strictly ambulatory. Forty-two
      patients required overnight admission, mostly due to social factors, and five
      patients required admission after 24-48 hours. Intraoperative variables
      predictive of postoperative admission were an operating time of more than 60
      minutes (p = 0.011), gallbladder dissection with anatomic difficulty (p = 0.001),
      and cystic artery hemorrhage (p = 0.041). Surgical access to the abdominal
      cavity, gallbladder perforation, trocar wound or hepatic bed bleeding, intensity
      or grade of hemorrhage, and gallbladder extraction were not predictive variables.
      CONCLUSIONS: Ambulatory laparoscopic cholecystectomy is a safe and effective
      procedure. Operating time, correct dissection of gallbladder structures and
      hemorrhage of the gallbladder hilus, especially of the cystic artery, play a
      major role in the success or failure of ambulatory laparoscopic cholecystectomy.

PMID- 16420819
TI  - [Impact of conservative oncoplastic techniques in a surgery program for women
      with breast cancer].
AB  - OBJECTIVES: To evaluate the impact of conservative oncoplastic techniques in a
      surgery program for women with breast cancer. PATIENTS AND METHOD: The study
      group was composed of women who underwent a conservative oncoplastic technique
      and the control group consisted of women who underwent conservative
      (tumorectomy/quadrantectomy) and radical (mastectomy) techniques. Women with
      tumors smaller than 3 cm, axillary clinical stages N0-N1a-b and multifocal
      processes (infiltrating and/or in situ) were eligible for inclusion. Women with
      T3-4 tumors and reduced breast volume, and those in whom postoperative
      radiotherapy and disease-free margins during intraoperative study were not
      feasible were excluded. RESULTS: One hundred sixty women underwent surgery during
      the study period. Fifty oncoplastic techniques (29 to avoid mastectomy and 21 to
      improve the result of a conservative technique), 57 conservative techniques and
      53 mastectomies were performed. The techniques used for breast reconstruction
      were superior mammoplasty with transversal scar (23 patients), mammoplasty with
      superior pedicle (10 patients), mammoplasty with inferior pedicle (10 patients),
      J-shapped mammoplasty (four patients) and oblique mammoplasty (three patients).
      The mean operating time in the group undergoing oncoplastic techniques (131
      minutes) was higher than that in the group undergoing conservative (56 minutes)
      and radical (93 minutes) techniques. The incidence of postoperative complications
      was higher with radical techniques (35%), mainly due to axillary seromas after
      lymphadenectomy, than with conservative (25%) and oncoplastic (24%) techniques.
      CONCLUSIONS: Oncoplastic techniques are an effective and efficient alternative to
      conventional surgical techniques in women with breast cancer.

PMID- 16420820
TI  - [Inappropriate hospitalization use in general surgery wards. Magnitude,
      associated factors and causes].
AB  - OBJECTIVE: To determine the proportion of inappropriate days of hospitalization
      in the general surgery wards of three university hospitals, its causes, and
      associated factors. MATERIAL AND METHOD: We concurrently reviewed 596 days of
      hospitalisation during a 1-week period in 2000, using the Appropriateness
      Evaluation Protocol (AEP). The association among inappropriate days of hospital
      stay and independent variables was evaluated using bivariable and multivariable
      methods. Finally, the causes for inappropriate hospitalization use were analyzed.
      RESULTS: The percentage of inappropriate days was 17.6%, with no significant
      differences among the hospitals (21.5%, 12.5% and 17.5%). Inappropriate days were
      associated with the weekend (odds ratio [OR] = 2.1, scheduled admissions (OR =
      2.9), hospital stay of more than 1 week (OR:2.3), the last third of the hospital
      stay (OR: 3.7), and inappropriate admission (OR: 2.1). The main causes of
      inappropriate hospital stays were organizational problems in the hospital or in
      the clinical management of discharge. CONCLUSIONS: Inappropriate days of
      hospitalization represent a considerable percentage of hospitalization in surgery
      wards. The main reasons for inappropriate days are problems with surgical and
      discharge planning and factors that depend on the organization of the surgery
      departments and other related departments in the hospital.

PMID- 16420821
TI  - [Biliary adenocarcinoma arising from atypical benign lesions].
AB  - Tumors of the biliary tract have a poor prognosis. When these tumors arise from a
      prior benign lesion the prognosis improves. We present two cases of carcinoma
      developing from atypical benign lesions. Aggressive surgical treatment was
      provided.

PMID- 16420822
TI  - [Intravenous iron in general surgery].
AB  - Preoperative anemia is the main cause of blood transfusion in surgical patients.
      In digestive surgery high blood loss and allogenic blood transfusion (ABT) are
      associated with serious adverse events and higher mortality. Consequently, we
      believe that intravenous iron administration is justified to correct
      perioperative anemia. We present the case of a woman with metastatic colorectal
      adenocarcinoma in whom intravenous iron administration avoided the use of ABT.
      Subsequently, the iron metabolism profile improved. This had previously
      corresponded to a mixed pattern of iron deficiency, that is, to the association
      of organic and functional iron deficiency.

PMID- 16420823
TI  - [Technology of the future applied to the present: Life Support for Trauma and
      Transport (LSTAT)].
AB  - One of the most recent innovations coalescing computer technology and medical
      care is the development of integrated medical component technology coupled with a
      computer system. One such example is the patient transport system known as the
      Life Support for Trauma and Transport (LSTAT). LSTAT is a self-contained
      stretcher-based intensive care unit designed by the United States Army to provide
      care for critically injured patients during transport and in remote settings
      where resources are limited. It contains conventional medical equipment that has
      been reduced in size and integrated into a single platform. This article presents
      the latest technology applied to the field of medicine, which should not be
      limited to patients injured during warfare but should also be used to assist the
      injured civilian population who need transport from remote settings to urban
      trauma centers.

PMID- 16420824
TI  - [A single gallbladder calculus occupying the entire gallbladder].

PMID- 16420826
TI  - [Laparoscopic repair of incisional hernias].

PMID- 16420827
TI  - [Informed consent in emergency surgery: a challenge].

PMID- 16420828
TI  - [New scenarios in liver transplantation].

PMID- 16420829
TI  - [Expert opinion on the basic surgical technique for laparoscopic ventral hernia
      repair].
AB  - Laparoscopic ventral hernia repair is currently the subject of intense debate,
      even though it provides a series of advantages over open surgery and is feasible
      and safe. Various studies have shown this technique to be as effective as open
      repair with a lower recurrence rate. Despite the excellent results of
      laparoscopic repair of ventral hernias, there are numerous controversies
      associated with this procedure. These controversies concern the indications and
      contraindications of the procedure, and technical aspects such as how to create
      the pneumoperitoneum, perform adhesiolysis, manage the hernia sac, and insert and
      fix the mesh to the anterior abdominal wall. Also controversial are outcome,
      complications related to postoperative seroma, and which type and size of mesh
      should be used. The present article aims primarily to address many of these
      issues, based on the experience of distinct surgeons with expertise in this
      approach, in order to provide data to establish a consensus on how laparoscopic
      ventral hernia repair should be performed.

PMID- 16420830
TI  - [Basic concepts in survival analysis].
AB  - The present article aims to introduce and explain basic concepts in survival
      analysis. Most survival analyses use terms such as Kaplan-Meyer, logrank, and
      censored times, among others. We discuss the background to these terms and their
      interpretation. We discuss how to produce and interpret survival curves and how
      to compare them. Finally, we explain some conditions that should be borne in mind
      when performing a survival analysis.

PMID- 16420831
TI  - [One thousand liver transplants. Hospital Clinic i Provincial de Barcelona
      (Spain)].
AB  - The aim of this study was to evaluate a consecutive series of 1000 liver
      transplants performed in our institution and to evaluate changes over time in
      donors and recipients, as well as results. MATERIAL AND METHOD: To clearly
      evaluate the differences between the initial transplantation period and the
      present period, the first 100 consecutive liver transplantations performed (June
      1988-June 1990) and the last 200 consecutive liver transplantations performed
      (January 2001-June 2003) were compared. RESULTS: Donor age increased (23+/-10 vs.
      45+/-19), the etiology of brain death changed (severe head injury: 78% vs. 23.5%;
      stroke: 17% vs. 52.5%) and the percentage of donors from alternative methods to
      cadaveric donors increased (living donors: 12.5%) in the second period. Regarding
      recipients, the piggy-back technique and biliary anastomosis without T-tube were
      introduced in the second period. Actuarial 1-year survival was higher in the
      second period than in the first (84% vs. 91.3%). The need for retrasplantation in
      the entire series was 9.5%, with actuarial survival at 1, 5 and 10 years of
      67.7%, 51.3% and 39.4%, respectively. CONCLUSION: Because of the lack of donors
      and the greater number of patients on the waiting list, poorer quality donors and
      more critical recipients have been accepted and alternative and innovative
      programs have been started. Nevertheless, due to improvement in patient
      management before, during and after transplantation, the previous good results
      have been maintained.

PMID- 16420832
TI  - [Laparoscopic resection of solid liver tumors. Presentation of our experience].
AB  - INTRODUCTION: Laparoscopic liver resection (LLR) of solid liver tumors (SLT) has
      not become widespread due to technical problems, the risk of air embolism, and
      possible tumoral spread in malignant lesions. We present our experience of LLR in
      SLT. PATIENTS AND METHOD: Between January 2003 and May 2005, we performed the
      laparoscopic approach in 16 patients with SLT. Preoperative diagnosis was liver
      metastases from colorectal carcinoma in 11 patients and benign tumor in the
      remaining five patients. Five of the lesions were located in the left lobe,
      another 10 in the right lobe (two in S. V, four in S. VI and four in S. VII) and
      the remaining lesion was bilobar (S. III and VI). LLRs were performed by complete
      laparoscopic hepatectomy (CLH) (n=8) and assisted laparoscopic hepatectomy (ALH)
      (n=8). LLR was completed in 13 patients (81%). Surgical technique (n=13)
      consisted of three left lobectomies, one with partial resection of S. IV, three
      bisegmentectomies (two of S. VI and VII and one of S. III and IV, the latter
      associated with metastasectomy in S. VIII), five segmentectomies (one of S. II,
      two of S. V and two of S. VI, one of the latter associated with metastasectomy in
      S. VII) and two local resections of benign tumors. RESULTS: There was no intra-
      or postoperative mortality. With CLH the LLR was completed in five patients
      (62%), whereas with ALH there were no conversions. Only one of the 13 resected
      patients required transfusion. Seventeen nodules were excised in the 13 LLR, and
      12 of 17 required the Pringle maneuver. The mean length of hospital stay was 4.9
      days (3-14 days). Only one female patient (7.7%) developed an infected hematoma,
      requiring radiological drainage. CONCLUSION: LLR of benign SLTs shows all the
      advantages of laparoscopy. In the case of malignant lesions, greater experience
      is needed to confirm the safety and effectiveness of the open approach.

PMID- 16420833
TI  - [Visceral artery aneurysms].
AB  - INTRODUCTION: The aim of this study was to review our experience in the diagnosis
      and treatment of visceral artery aneurysms. MATERIAL AND METHOD: We performed a
      retrospective study through review of the medical records of patients diagnosed
      with visceral aneurysms from 1984 to 2003. Diagnosis, treatment and follow-up
      were analyzed. RESULTS: Thirty-two aneurysms were diagnosed in 27 patients (17
      men and 10 women). There were 12 aneurysms of the splanchnic artery, six of the
      hepatic artery, five of the celiac trunk, three gastroduodenal, one jejunal, one
      pancreaticoduodenal, one superior mesenteric--associated with a splanchnic, renal
      and celiac trunk aneurysm--, one inferior mesenteric, one cystic artery and one
      case of parenchymatous hepatorenal microaneurysms. Eight aneurysms were not
      treated. Three underwent embolization. One aneurysm was excluded with a covered
      endoprosthesis. Twenty aneurysms were treated surgically. Ligature or exclusion
      was performed in 11 patients, hepatic lobectomy in one patient, resection with
      revascularization in four patients, endoaneurysmorrhaphy in three patients and
      simple suture was performed in one hepatic artery pseudoaneurysm. CONCLUSIONS:
      Current diagnostic techniques favor early and sometimes minimally invasive
      treatment. Splanchnic aneurysms are more difficult to diagnose and require highly
      varied repair techniques.

PMID- 16420834
TI  - [Thyroid carcinoma].
AB  - OBJECTIVES: To evaluate the results of surgical treatment in patients with
      thyroid carcinoma. MATERIAL AND METHOD: Eighty-five patients diagnosed with
      thyroid cancer between October 1970 and November 2004 were studied. Clinical
      presentation, diagnostic procedures, surgical treatment, histological diagnoses,
      complications and follow-up were analyzed. The information was processed using
      the BMDP statistical package. The results were analyzed using descriptive
      statistics: chi-square test and t-test to evaluate differences. Survival was
      analyzed using the Mantel-Cox test, with a value of P=0.05. RESULTS:
      Differentiated carcinoma was more frequent (usual variant in 84.5%; follicular
      carcinoma in 9.3% and tall cell carcinoma in 6.2%). Age: 48+/-5.48 years.
      Papillary carcinoma was diagnosed in younger patients than follicular carcinoma
      (p=0.03) and predominated in women aged less than 49 years. Symptoms were due to
      the presence of nodules in the neck, whether palpable or not. Seventy-four
      percent of nodules were non-echoic. Ultrasonography revealed the presence of a
      solitary nodule in 96%. Total thyroidectomy was performed in 82%, and hemi- or
      subtotal thyroidectomy was performed in 12%. Six percent of the patients received
      palliative treatment. Recurrence occurred in 6%. CONCLUSIONS: Mortality in
      thyroid carcinoma is related to histological type, age, sex, tumoral size, the
      presence of regional metastases and palliative treatment.

PMID- 16420835
TI  - [Endoscopic treatment of Zenker's diverticulum].
AB  - INTRODUCTION: We report our experience in the endoscopic (flexible) treatment of
      Zenker's diverticulum. PATIENTS AND METHOD: Three patients with medium-sized
      Zenker's diverticula were treated by endoscopic cricopharyngeal myotomy with a
      modified needle-knife sphincterotome through a therapeutic gastroscope. The
      procedure was performed in the digestive endoscopy unit under conscious sedation
      without anesthetic support. RESULT: Endoscopic cricopharyngeal myotomy was
      completed in a single session without immediate or late complications. In all
      three patients dysphagia disappeared and all were discharged at 48 hours with a
      solid diet. After 12, 18 and 17 months of follow-up there has been no recurrence
      of dysphagia or other symptoms attributable to Zenker's diverticulum. CONCLUSION:
      Flexible endoscopic cricopharyngeal myotomy is a simple, effective and safe
      treatment of Zenker's diverticulum that avoids the need for open cervical surgery
      and general anesthesia.

PMID- 16420836
TI  - [Utility and advantages of single tracer subareolar injection in sentinel lymph
      node biopsy in breast cancer].
AB  - INTRODUCTION: Sentinel lymph node (SLN) biopsy is a reliable technique for
      determining axillary status in patients with early breast cancer. This technique
      is a minimally invasive procedure that can avoid the use of lymphadenectomy in
      patients without axillary involvement. We present a validation study of SLN
      biopsy with subareolar injection of 99mTc-nanocolloids. MATERIAL AND METHOD: We
      studied 100 patients with early breast cancer (T1 and T2) over a 2-year period.
      All patients underwent deep subareolar-injection of 99mTc-nanocoloid for
      localization of the sentinel node. Images were obtained and when the sentinel
      node was seen, it was marked on the skin. All patients underwent tumor excision
      and radioguided SLN biopsy followed by complete lymphadenectomy.
      Histopathological analysis of sentinel nodes was performed by hematoxylin-eosin
      and immunohistochemistry with cytokeratins. RESULTS: The sentinel node was
      identified in all patients, and a mean of 1.95 sentinel nodes per patient were
      found. Lymphatic metastases in the sentinel node were found in 44 patients and in
      15 of these tumoral spread was also found in the remaining axillary nodes. In the
      56 remaining patients the sentinel node was free of metastasis, but in two of
      them a non-sentinel node was found to be positive (4.5% false negative rate).
      Sensitivity was 95.7% (44/46), specificity was 100% (54/54), the positive
      predictive value was 100% and the negative predictive value was 96.4% (54/56).
      CONCLUSIONS: SLN biopsy is an accurate alternative to complete axillary lymph
      node dissection in patients with early-stage breast cancer. This technique
      improves the staging of these patients and decreases the morbidity associated
      with lymphadenectomy. The advantages of subareolar injection are that a single
      injection site is required, the tumor does not have to be located by other
      techniques, it allows rapid visualization of the sentinel node and avoids the
      "shine through phenomenon" when the tumor is located near the axilla.

PMID- 16420837
TI  - [Noninvasive intracystic papillary carcinoma of the male breast. A case report].
AB  - Ductal carcinoma in situ (DCIS) represents between 0% and 7% of breast cancers
      diagnosed in men. Noninvasive intracystic papillary carcinoma is a form of DCIS
      and is therefore an extremely rare presentation of breast cancer. The imaging
      technique that provides the greatest information on these lesions is
      ultrasonography. Treatment of DCIS in men continues to be controversial. We
      present a case of noninvasive intracystic papillary carcinoma treated with
      partial mastectomy followed by radiotherapy and tamoxifen therapy. After 1 year
      of follow-up, the patient shows no signs of recurrence.

PMID- 16420838
TI  - [Gastric perforation due to trichobezoar in an adult (Rapunzel syndrome)].
AB  - Rapunzel syndrome, or trichobezoar, is an uncommon entity and secondary gastric
      perforation is exceptional. We found no adult cases reported in the literature.
      Our patient is a teenager with clinical symptoms of epigastric mass and acute
      abdomen. Radiological study showed pneumoperitoneum and intragastric mass.
      Personal history revealed depressive syndrome and anxiety. Urgent laparotomy
      confirmed the diagnosis of gastric perforation due to a trichobezoar completely
      moulding the gastric chamber. The diagnosis was suspected on the basis of
      radiologic images but laparotomy was required to confirm it.

PMID- 16420839
TI  - [Late breast metastases from an intestinal carcinoid tumor].
AB  - We present the case of a woman who underwent surgery for an ileal carcinoid tumor
      and who subsequently presented breast metastases. The rarity of this case is
      discussed and a literature review is presented.

PMID- 16420840
TI  - [Grade III chondrosarcoma].

PMID- 16420841
TI  - [Mucinous cystoadenoma of the pancreas and acute pancreatitis].

PMID- 16420842
TI  - [Spontaneous intramural hematoma of the small intestine].

PMID- 16420843
TI  - [Misread lesions in patients with multiple trauma].

PMID- 16420844
TI  - [Advantages and characteristics of the laparoscopic approach in the elderly].
AB  - Both the age of the population and anesthetic and surgical techniques are
      advancing. Currently, 40% of surgical activity is performed in patients older
      than 65 years, who present a higher surgical risk than younger patients. The aim
      of treatment in the elderly is to provide the best possible quality of life, even
      though this represents a surgical challenge because of associated comorbidity and
      reduced cardiopulmonary reserve. From the moment at which laparotomy becomes an
      increased stress in the elderly, laparoscopic surgery can be particularly
      advantageous in this population. Therefore, minimally invasive surgery may have a
      greater impact in these individuals than in younger patients in reducing
      postoperative pain, cardiorespiratory complications, hospital stay, and recovery
      time before resuming physical activity. The recent advances in anesthesia,
      together with improved patient selection and perioperative cardiac care, and the
      general adoption of minimally invasive access have enabled more complex
      gastrointestinal procedures to be performed in the elderly. The factors that
      could influence the development of this type of approach in the elderly, as well
      as the precautions that should be taken, should be further analyzed.

PMID- 16420845
TI  - [The university in the development of thoracic surgery in Spain].
AB  - The present article analyzes the figures of the university professors who, from
      1911, formed part of one of the basic pillars in the development of "Spanish
      Thoracic Surgery". At that time, there was a certain amount of infighting between
      general and specialized surgery, which was resolved by allowing specialization
      after a period of training in general surgery. Universities should not be denied
      the great merit of having produced well-trained surgeons with a broad general
      foundation who would later choose a specialty. The figures of Ricardo Lozano
      Monzon, Francisco Martin Lagos, Jose Gasco, Benjamin Narbona, Carlos Carbonell
      Antoli, Rafael Vara Lopez, Alfonso de la Fuente Chaos and Jose M. Beltran de
      Heredia with their previous training, corresponding precursors and respective
      schools are described. Their teaching, surgical practice, and scientific activity
      are also described. A future article based on the contribution of Valencia to the
      specialty of general thoracic surgery is also outlined.

PMID- 16420846
TI  - [Missed injuries in patients with multiple trauma: analysis of a trauma
      registry].
AB  - INTRODUCTION: The frequency of missed injuries (MI) in patients with trauma
      oscillates between 0.5 and 38%, depending on the distinct studies and their
      inclusion criteria. In the present study, we evaluated the incidence,
      contributory factors and clinical relevance of these lesions, based on the Severe
      Trauma Registry of our center. PATIENTS AND METHODS: We retrospectively analyzed
      a registry of 912 cases of severe trauma, which were prospectively gathered. Of
      these, 19 patients had a MI (2%). Demographic (age and sex) and clinical
      variables (severity scales and mechanism of injury) were compared and avoidable
      contributory factors and clinically relevant MI were evaluated. RESULTS: Of the
      19 patients with a MI, 58% had closed injuries. No statistically significant
      differences were found in any of the variables studied, although penetrating
      injuries were clearly more frequent in patients with MI than in those without.
      Forty-seven percent of MI were musculoskeletal, 26% were visceral and 21% were
      vascular. Sixty-three percent of contributory factors were potentially avoidable
      and the most frequent reason for MI was incorrect clinical evaluation. Mortality
      due to lesions with a delayed diagnosis was 21%. CONCLUSIONS: Incorrect clinical
      evaluation was the avoidable factor that would have the greatest impact on
      reducing the number of MI. Another factor that clearly contributes to reduction
      of MI is appropriate interpretation of radiological images in the context of a
      tertiary survey. All teams treating these patients should periodically evaluate
      their results and intervene in the factors contributing to missed diagnoses.

PMID- 16420847
TI  - [Emergency surgery in severe lower gastrointestinal hemorrhage].
AB  - INTRODUCTION: There are no conclusive studies that would allow us to distinguish
      between patients with severe lower gastrointestinal hemorrhage (LGIH) who require
      emergency surgery and those who do not. The aim of the present study was to
      determine the clinical and epidemiological factors that would allow us to
      distinguish between severe LGIH requiring emergency surgery and self-limiting
      LGIH and to analyze the surgical management of these patients. MATERIAL AND
      METHODS: We reviewed 175 patients with LGIH (severe rectal bleeding with a
      decrease in hematocrit > or = 10 points or transfusion of at least three units of
      packed red blood cells) treated between 1980 and 2002 and selected 28 patients
      (16%) who required emergency surgery. The control group consisted of patients
      with LGIH who did not require surgery. Student's t-test and the Chi-squared test
      were used in the statistical analysis. RESULTS: Comparison of severe LGIH
      requiring emergency surgery with self-limiting LGIH revealed three variables that
      could serve as a guide to differentiating between these entities, namely: age
      less than 80 years (p = 0.013), the presence of hypotension on arrival at the
      emergency department (p < 0.0001), and cause of bleeding (p < 0.0001). Among
      patients requiring emergency surgery, the origin was ano-rectal in nine (32%) and
      consequently the approach used was perianal. In the remaining patients (n = 19)
      the abdominal approach was used. In 10 patients, etiologic diagnosis was not
      available before surgery and the source of bleeding was identified during the
      intervention in 6 of these patients. In the four remaining patients without
      etiological diagnosis before surgery, subtotal colectomy was performed. In the
      remaining patients, local resection of the affected area was performed (3 right
      hemicolectomies, 9 small bowel resections, and 3 resections of Meckel's
      diverticulum). Morbidity was 18% and mortality was 7%. CONCLUSION: Distinguishing
      between self-limiting LGIH and LGIH requiring emergency surgery is difficult. In
      our series, the only factors predictive of emergency surgery were hemodynamic
      instability on arrival at the emergency department and age less than 80 years.
      Cause of bleeding is not a predictive factor as it generally unknown at symptom
      onset.

PMID- 16420848
TI  - [Adverse outcomes in the surgical treatment of acute appendicitis].
AB  - OBJECTIVES: To describe adverse outcomes after appendectomy for acute
      appendicitis and to analyze the association between these outcomes and specific
      characteristics of the patient and hospital admission. MATERIAL AND METHODS: We
      studied a cohort of 792 patients who underwent appendectomy for acute
      appendicitis. Postoperative complications, reoperations and deaths were
      prospectively studied and all readmissions were retrospectively identified.
      Logistic regression was used to evaluate the relationship between complications
      and patient characteristics, as well as hospital admission. RESULTS: Postsurgical
      complications developed in 9.8% of the patients. These complications mainly
      consisted of surgical wound infection (4.2%) and intra-abdominal complications
      (2.1%). A total of 0.7% of patients underwent reoperation during admission, 0.5%
      were admitted to the intensive care unit and five patients (0.6%) died in
      hospital. The rate of operation-related readmissions in the following year was
      3.2%. Length of hospital stay was longer in patients with complications than in
      those without complications (9.6 and 3.5 days, respectively). Postoperative
      complications were associated with older age (45-65 years, OR 3.62, p < 0.001;
      more than 65 years OR 8.68, p < 0.001) and acute appendicitis complicated with
      peritonitis or perforation (OR 3.69, p < 0.005). Readmissions related to previous
      surgery were associated only with complications during the first admission (OR
      18.79, p < 0.001). CONCLUSIONS: In appendectomy, the most frequent adverse
      outcomes are surgical wound infection and intra-abdominal complications, which
      are associated with older patients and perforations. This subgroup of patients at
      high risk requires closer surveillance.

PMID- 16420849
TI  - [Surgical treatment of liver metastases from breast cancer].
AB  - INTRODUCTION: A small number of patients with breast cancer develop liver
      metastases (LM) as the sole site of regional dissemination. In these patients,
      surgical resection seems to be the best therapeutic option. We present our
      experience of LM from breast cancer and discuss the indications for resection.
      MATERIAL AND METHODS: Between July 2003 and March 2005, we performed five
      hepatectomies for LM from breast cancer. The mean age was 51 years (range: 38
      66). Patients received diverse combinations of chemotherapy, hormone therapy and
      radiotherapy after mastectomy. The disease-free interval between mastectomy and
      diagnosis of LM was 61 months (range: 36-80). The number of LM was 1.83 (range: 1
      6) with a median of one LM. The mean size was 4.1 cm (range: 1.5-6). RESULTS:
      Surgery consisted of segmentectomy (three patients), bisegmentectomy (one
      patient), right hepatectomy associated with isolated metasectomies of the left
      lobe and hilar lymphadenectomy (one patient). Operative mortality was 0%.
      Morbidity was 20% (one patient). The mean length of hospital stay was 8 days. The
      mean length of follow-up was 11.4 months (range: 3-21). The mean survival was
      11.4 months (range: 3-21). Disease-free survival was 9.6 months (range: 3-21).
      Two patients have had recurrence (one local and one regional). CONCLUSIONS: Given
      its characteristics, LM from breast cancer is an infrequent indication for liver
      resection and should be performed whenever technically feasible, whenever R0
      resection can be achieved, and when there is low operative risk. Postoperative
      survival is better with resection than with any other therapeutic modality, even
      though the period of disease-free survival is short.

PMID- 16420851
TI  - [Etiology and diagnosis of severe retroperitoneal hematoma: therapeutic options
      and surgical indication].
AB  - Retroperitoneal hematoma is a rare entity with clinical consequences that vary
      according to the speed and amount of bleeding. Thus, it may be asymptomatic, in
      which case it is usually diagnosed incidentally through imaging tests, or severe,
      in which case the most common symptoms are pain and hypovolemic shock. We report
      three cases of severe retroperitoneal hematoma. Although the literature on the
      subject describes a wide variety of causes, in all three patients the etiology
      was tumoral, consisting of one suprarenal myelolipoma, one renal adenocarcinoma
      and one suprarenal metastasis from bronchogenic adenocarcinoma. Computed
      tomography was the imaging test employed not only to determine the nature of the
      process (hematoma, abscess, tumor) but also to assess compression of adjacent
      structures and the occurrence of active bleeding. Conservative treatment
      consisting of volemic replacement and correction of coagulation was initially
      attempted. However, all three patients required emergency surgery due to
      hemodynamic instability in two patients and compression of the vena cava in the
      other.

PMID- 16420850
TI  - [Influence of superspecialization in endocrine surgery on outcomes of
      thyroidectomy in a general surgery department].
AB  - INTRODUCTION: The aim of this study was to analyze the influence of
      superspecialization in endocrine surgery on the standard of thyroidectomy, both
      before and after the creation of an endocrine surgery unit. PATIENTS AND METHODS:
      We performed a retrospective, comparative study of two 7-year periods. Three
      hundred forty thyroidectomies (G1) were performed before the instauration of the
      unit, and 583 were carried out afterwards (G2). The variables of age, gender,
      anesthesia risk, surgeon expertise (staff vs. resident), thyroid function,
      pathological features, intrathoracic growth, extent of the procedure (unilateral
      or bilateral), neck drainage, morbidity and mortality and length of hospital stay
      were compared. RESULTS: Age was older in G2 (G1: 44.7 +/- 15 years old, G2: 48.09
      +/- 16.3 years old; p < 0.001). There were no differences (p NS) between the two
      groups in gender, anesthesia risk, thyroid function or rate of benign/malignant
      disease, but there was a greater frequency of nodular (p = 0.009) and
      intrathoracic goiters (p = 0.0004) in the second period. Residents operated on
      more patients in G2 (p < 0.001). Bilateral thyroidectomy was more frequent in G2
      (G1: 155, G2: 315; p = 0.016) as was the rate of total thyroidectomy vs. subtotal
      or near total thyroidectomy (p < 0.001). Neck drainage also showed statistically
      significant differences (G1: 75.29%, G2: 12.18%; p < 0.001). No differences were
      found in overall postoperative complications. Although the procedures used were
      more aggressive in G2, similar rates of transient asymptomatic hypocalcemia (p
      NS) and transient symptomatic (p NS) and permanent hypocalcemia were found (G1:
      1.17%, G2: 0.68%, p NS). The rate of transitory recurrent laryngeal nerve
      paralysis was similar with regard to patients (p NS) or nerves at risk (p NS).
      Permanent inferior laryngeal nerve paralysis was no different regarding patients
      (p = 0.083) but statistically significant differences were found with regard to
      nerves at risk (G1: 1.44%, G2: 0.33%; p = 0.04). One patient in G2 died (p NS).
      Length of hospital stay was shorter in G2 (p < 0.001) and more patients in this
      group stayed in hospital for only one day (p < 0.001) or were operated on in the
      outpatient setting (0 versus 71; p < 0.001). CONCLUSIONS: An endocrine surgical
      unit allows more efficient management of thyroidectomy. It increases the rate of
      total thyroidectomy, reduces definitive complications and improves training of
      resident surgeons. In addition, it reduces resource use and allows the
      development of programs of outpatient thyroid surgery.

PMID- 16420852
TI  - [Absence/disappearance of gallbladder in a patient diagnosed with
      cholelithiasis].
AB  - We report the case of a patient with preoperatively demonstrated cholecystitis
      due to cholelithiasis but with no presence of gallbladder at laparoscopy or on
      conversion to open surgery. Gallbladder ectopy was ruled out and the possibility
      of gallbladder agenesia was discussed. However, four preoperative ultrasound
      scans performed within a protocol of treatment with octreotide, in the setting of
      acute cholecystitis, ruled out this possibility. We discuss the possibility of
      gallbladder destruction and digestion after a severe inflammatory process, as
      well as Frey's criteria for gallbladder agenesia. We believe that this is a case
      of complete gallbladder lysis due to an inflammatory process.

PMID- 16420853
TI  - [Crohn's disease of the appendix].
AB  - Crohn's disease limited to the appendix is uncommon. Clinically, it is likely to
      mimic acute appendicitis. It is more frequent in young people and definitive
      diagnosis is histological. We present a series of seven cases of Crohn's disease
      of the appendix that were treated in our surgery service over the past 12 years.
      The seven patients had pain in the lower right quadrant. In all patients, the
      preoperative diagnosis was acute appendicitis and appendectomy was performed.
      Histopathological evaluation was required for diagnosis. In the postoperative
      course, one patient was diagnosed with colonic Crohn's disease, and outcome was
      favorable with medical treatment. Although isolated Crohn's disease of the
      appendix is a rare entity, it should be considered in the preoperative
      differential diagnosis of patients with right lower quadrant pain and a
      protracted preoperative course mimicking acute appendicitis. Disease recurrence
      elsewhere in the alimentary tract is uncommon.

PMID- 16420854
TI  - [Image of the month. Abdominal muscle hematoma].

PMID- 16420855
TI  - [Treatment of chronic anal fissure].

PMID- 16420856
TI  - [Solitary fibrous tumor of the pleura].

PMID- 16420858
TI  - [Cytoreductive surgery and perioperative intraperitoneal chemotherapy for
      neoplasms with peritoneal dissemination: the time has come].

PMID- 16420859
TI  - [Local recurrence in colon and rectal cancer].
AB  - Data on the incidence of colorectal cancer are alarming and reveal that it is
      currently the second cause of death from cancer. Most of these deaths are due to
      recurrence after surgery with curative intent. The factors associated with
      locoregional recurrence are mainly related to the tumor's histopathological
      characteristics and grade of invasion. With adequate training the surgeon should
      not appear among these factors. In rectal cancer this training involves the
      technique of mesorectal excision, adequate circumferential margin and selective
      neoadjuvant chemoradiotherapy. After curative resection, patients should be
      followed-up to detect asymptomatic recurrence. Isolated local recurrence occurs
      in 20-30% of patients, but even with liver or lung metastases curative surgery
      can be attempted and success depends on correct multidisciplinary preoperative
      evaluation. If the diagnosis is made when the tumor is in an incurable phase, the
      aim is to improve the patient's quality of life.

PMID- 16420860
TI  - [On how to analyze the credibility of a clinical trial or meta-analysis whose
      main result is expressed in odds ratio, relative risk or hazard ratio].
AB  - Beyond the type of design or the statistical analysis applied, the credibility of
      a research study lies in the compatibility of its results with the intensity that
      the reader could accept that the phenomenon studied might have from a biological
      point of view. Ultimately this requires a value judgment. The present article
      describes a procedure that can be used to objectively approach the limits of
      intensity that that a biological phenomenon could have, according to the data
      presented, so that, based on the reader's judgment derived from the available
      knowledge of the problem, the study can be deemed credible. The procedure is
      valid when the results of the study are expressed in odds ratio, relative risk or
      hazard ratio. Although these statistics are difficult to interpret, they are
      probably the most widely used in clinical trials and meta-analyses, that is, in
      studies whose methodological designs provide the highest level of evidence.

PMID- 16420861
TI  - [Assessment of the fifth edition of the tumor-node-metastasis (TNM)
      classification for gastric cancer in our setting].
AB  - AIM: To estimate the proportion of patients with gastric carcinoma that can be
      classified using the criteria of the fifth edition of the TNM system and to
      analyze which factors could be related to the finding of an adequate number of
      nodes. PATIENTS AND METHOD: The influence of distinct factors that could
      influence the number of lymph nodes isolated was evaluated in 164 patients who
      underwent resection of gastric carcinoma. These factors included tumor size,
      surgical resection, grade, histological type, variability among the pathologists
      who analyzed the surgical specimens, and the surgeon's experience. RESULTS: The
      mean number of lymph nodes examined by the pathologists was 11.4 (10.12-12.66).
      Applying the criteria of the fifth edition of the TNM classification, only 31% of
      the patients could be correctly classified. A positive correlation was found
      between tumor size and the number of resected nodes (p = 0.0018). In addition, a
      greater number of lymph nodes were found in total gastrectomies than in subtotal
      gastrectomies (p = 0.034). No significant association was found with the
      pathologist who analyzed the surgical specimen or with the experience of the
      surgeon who performed the resection. CONCLUSIONS: The fifth edition of the TNM
      system is easily reproducible, although the number of lymph nodes required to
      evaluate metastatic node involvement is difficult to obtain in our environment.
      Our results suggest that a combined effort between surgeons and pathologists is
      needed to increase the number of patients that can be reliably staged with this
      TNM edition.

PMID- 16420862
TI  - [Resection of lung metastases from colorectal cancer].
AB  - OBJECTIVES: To evaluate clinically relevant prognostic factors and to define a
      subgroup of patients who would most benefit from resection of lung metastases.
      PATIENTS AND METHOD: Between July 1978 and April 2004, 125 patients with
      pulmonary metastases from colorectal cancer who underwent lung resections were
      prospectively followed-up. The median follow-up was 32.4 +/- 3.2 months. Patients
      with no evidence of extrathoracic recurrence, no more than three metastases on
      either side, and adequate cardiorespiratory function were eligible for surgery.
      The most frequent procedure was lobectomy. Univariate and multivariate analyses
      were performed, with a value of p = 0.05. RESULTS: A total of 54.4% of the
      patients were men. The median age was 53.04 +/- 11.5 years. Survival rates at 3
      and 5 years were 47% and 27% respectively. The independent prognostic factors
      identified were size of metastases and extent of resection. Subgroup analysis
      defined two statistically relevant prognostic groups: patients with metastases
      sized 3.75 +/- 2.3 cm or less with a disease-free interval of more than 10 months
      and patients with larger metastases and a shorter disease-free interval.
      CONCLUSIONS: Subgroup analysis provided criteria for the selection of patients
      for resection of lung metastases from colorectal cancer and differentiated
      between those at high and low risk of early tumor progression.

PMID- 16420863
TI  - [Predictive factors for malignancy in breast microcalcifications without
      associated lesions].
AB  - INTRODUCTION: Screening mammography allows the early detection and treatment of
      nonpalpable carcinomas. Microcalcifications are highly important for the
      detection of many of these malignancies but are also present in benign breast
      disease. In the present study we analyzed the radiologic and clinical factors
      associated with malignancy. MATERIAL AND METHODS: We retrospectively reviewed 133
      patients who underwent open biopsy after a mammographic finding of
      microcalcifications without an associated lesion. Clinical and radiologic
      characteristics were correlated with histologic findings. RESULTS: A total of
      28.6% of the lesions analyzed were malignant. Of these, 65.8% were ductal
      carcinoma in situ. Among invasive carcinomas, 23.1% presented lymph node
      metastasis. No clinical criterion was significant for malignancy. On univariate
      analysis six radiologic criteria were significant: morphologic type (Le Gal's
      classification), irregularity of size, irregularity of density, number of
      microcalcifications per cluster, diameter of the lesion, and the presence of more
      than one cluster. On multivariate analysis the factors with independent
      predictive value were: irregularity of density, > or = 10 microcalcifications per
      cluster, the presence of more than one cluster, and diameter of the cluster > or
      = 10 mm. CONCLUSIONS: Although none of the clinical factors analyzed was
      predictive for malignancy, the radiological characteristics of
      microcalcifications were determining factors in the indication for biopsy.

PMID- 16420864
TI  - [Laparoscopic appendicectomy and pregnancy. Personal experience and review of the
      literature].
AB  - INTRODUCTION: Pregnancy has been considered to be an absolute contraindication to
      the laparoscopic approach because of the theoretical effects of the
      pneumoperitoneum on the fetus and the occupation of the working space by the
      gravid uterus. Despite the growing literature on the subject, experience with
      frequent entities, such as acute appendicitis, is limited. OBJECTIVE: The aim of
      this study was to report our experience with laparoscopic appendicectomy in
      pregnancy, to review the scientific evidence available on the safety of this
      procedure, and to establish the most relevant practical features for the use of
      this approach during pregnancy. MATERIAL AND METHODS: We retrospectively reviewed
      six laparoscopic appendectomies performed in pregnant women. We also reviewed the
      available literature on well documented laparoscopic appendectomies during
      pregnancy. RESULTS: All the procedures were laparoscopically completed. The mean
      operating time was 46 min. All patients were discharged within the first 48
      postoperative hours. There were no surgical complications. All patients delivered
      healthy infants with appropriate weight for gestational age. For the literature
      review, 17 references were collected that included data on 94 laparoscopic
      appendectomies performed in pregnant women. There was only one fetal death
      associated with the surgical approach and the overall fetal mortality rate was
      less than that classically registered in the literature for the open approach.
      CONCLUSIONS: Laparoscopic appendectomy in pregnant women is as safe and effective
      as the open approach and confers all the benefits of minimally invasive surgery.

PMID- 16420865
TI  - [Polypropylene and polydioxanone show similar biomechanical efficacy in midline
      closure].
AB  - INTRODUCTION: After laparotomy, the incidence of incisional hernia is high,
      especially when the abdomen in opened along the linea alba, a weak structure of
      the abdominal wall. This study was designed to evaluate the biomechanical
      resistance of midline closure using the same surgical technique but two different
      types of suture material, a long-lasting absorbable material and a non-absorbable
      material. MATERIAL AND METHODS: A 7.5 cm midline laparotomy was performed in 48
      New Zealand White rabbits. The surgical wound was then repaired with an en masse
      running suture using polypropylene 4/0 or polydioxanone 4/0. Animals not
      subjected to surgery were used as controls. Morphological, immunohistochemical
      and biomechanical tests were undertaken 3 weeks, 6 weeks and 6 months after
      surgery. RESULTS: Both types of suture gave rise to scar tissue composed of
      collagen fibers concentrically arranged around the suture filaments. Six months
      after surgery, the polydioxanone suture had almost completely degraded. The
      macrophage response steadily diminished over time, although it was significantly
      greater in wounds closed by polydioxanone suture. No significant differences were
      found in the biomechanical strength provided by the two types of suture.
      CONCLUSIONS: After laparotomy closure at the linea alba, both suture materials
      showed optimal biological behavior. The composition of the suture material did
      not affect the tensile strength of the repair zone.

PMID- 16420866
TI  - [Stewart-Treves syndrome].
AB  - Lymphangiosarcoma is an uncommon vascular tumor that usually develops in
      longstanding lymphedema. We gathered the cases of lymphangioma observed in a
      hospital and attempted to analyze their characteristics: age, sex, localization,
      treatment and follow-up data. We studied five cases: three cases of Stewart
      Treves syndrome after mastectomy and radiotherapy and two cases that developed in
      patients with late-onset congenital lymphedema. There were four women and one
      man. Radical surgery was performed in four patients. The techniques employed
      were: above-knee amputation (one patient), hip disarticulation (one patient),
      scapulo-humeral disarticulation (two patients) and gemcitabine and radiotherapy
      in one patient with metastatic disease at diagnosis. Three patients died in the
      first 14 months of follow-up, while two are disease free after 46 and 86 months
      respectively. This study confirms the poor prognosis of patients with Steward
      Treves syndrome.

PMID- 16420867
TI  - [Intestinal occlusion due to cecal volvulus].
AB  - Cecal volvulus is uncommon in the West and represents only 1% of cases of
      intestinal occlusion in adults. We describe three cases of intestinal occlusion
      due to cecal volvulus in two women aged 74 and 61 years old and a man aged 81
      years old with multiple pathological antecedents. The patients had pain,
      abdominal distension and absent feces. They were treated surgically with right
      hemicolectomy and mechanical ileocolonic anastomosis. The postoperative course
      was favorable in the two women but the man died. The two female patients are
      currently able to perform appropriate social and occupational activities for
      their age and underlying diseases.

PMID- 16420868
TI  - [Central pancreatectomy in benign tumors of the neck of the pancreas].
AB  - The surgical treatment of benign tumors of the neck of the pancreas usually
      consists of enucleation or formal pancreatectomy. Central pancreatectomy has been
      put forward because it has fewer major complications and can preserve endocrine
      and exocrine function. Between January 1999 and march 2003, three patients with
      benign tumors of the neck of the pancreas underwent central pancreatectomy. all
      patients underwent computed tomography scans, intraoperative ultrasound and
      frozen-section analysis. pathologic examination showed two mucinous cystadenomas
      and one serous cystadenoma. after a mean follow-up of 34 months, none of the
      patients has shown major complications or local recurrence, or has developed
      diabetes. In conclusion, central pancreatectomy is a useful technique for
      selected benign or low-grade malignant pancreatic tumors of the neck of the
      pancreas.

PMID- 16420869
TI  - [Tumor compatible with adrenal cortex carcinoma].

PMID- 16420870
TI  - [Intestinal malrotation after childhood].

PMID- 16420871
TI  - [Morbidity and transfusion: homogenizing series].

PMID- 16420872
TI  - [Massive spontaneous hemothorax].

PMID- 16420873
TI  - [Intestinal pneumatosis and portal gas secondary to adhesional obstruction].

PMID- 16420874
TI  - [The development of a surgical education program].

PMID- 16420875
TI  - [The need for changes in surgical training: an unresolved problem in endoscopic
      surgery].

PMID- 16420877
TI  - [Gallbladder adenocarcinoma: tumoral staging, histological prognostic factors and
      survival].
AB  - INTRODUCTION: Gallbladder adenocarcinoma is an aggressive tumor and is one of the
      digestive tract malignancies with the poorest prognosis. Because of loco-regional
      extension and delayed diagnosis, curative resection is often impossible. To
      determine histological prognostic factors and survival in relation to tumoral
      stage at diagnosis, we performed a retrospective study of our patients with
      gallbladder carcinoma. PATIENTS AND METHOD: Sixty-two patients with gallbladder
      adenocarcinoma diagnosed over a 15-year period were retrospectively included in
      this study. The surgical procedures performed in this group of patients were
      laparoscopic cholecystectomy, open cholecystectomy and palliative surgery in
      patients with unresectable tumors. For each tumoral stage, age, sex, cellular
      differentiation, tumor size, the presence of metastatic nodes, histological
      variables linked to poor prognosis, and survival were compared. RESULTS: Of the
      62 patients included, 45 were women and 17 were men. The mean age was 75 years.
      No significant differences were found in relation to age or sex among the
      different tumoral stages. Cellular differentiation and survival were poorer with
      advanced tumoral stage. A significant predominance of histological factors of
      poor prognosis was found in T2 and T3 tumors. CONCLUSIONS: Preoperative diagnosis
      of gallbladder adenocarcinoma is difficult except in advanced cases. It is often
      incidentally diagnosed at histological examination of gallbladders, and shows
      little local advancement and a good degree of cellular differentiation. The
      etiology of this tumor is unknown but its prevalence is greater among women.
      Clinical symptoms are similar to those caused by gallstones. In this study no
      relationship was found between age and sex and tumoral stage. In advanced tumoral
      stages poor cellular differentiation is predominant as well as other histological
      markers of poor prognosis. Good survival was found in T3 tumors, possibly linked
      to good cellular differentiation. Due to high associated comorbidity, none of the
      patients underwent reintervention.

PMID- 16420876
TI  - [Principles of the treatment of peritoneal carcinomatosis due to colorectal
      cancer. Current review and update].
AB  - Colorectal cancer is the most frequent digestive tumor. The incidence of
      abdominal dissemination is high and all studies of the natural history of
      colorectal carcinomatosis demonstrate that prognosis in these patients is poor,
      with a mean survival of between 5 and 9 months. Furthermore, the results of
      systemic adjuvant treatment are disappointing, with a maximum survival of 18
      months. Consequently, other treatment strategies need to be studied and
      developed. We present a review of the principles that underlie Sugarbakers
      treatment protocol, which includes maximal cytoreductive surgery for the
      treatment of macroscopic disease through peritonectomy together with
      perioperative intraperitoneal intensification chemotherapy for residual
      microscopic disease. We present all the phase II studies with more than 10
      treated patients published in the medical literature by the main groups working
      in this line of treatment, together with the only phase III study published to
      date. With this new therapeutic alternative, the mean overall survival at 2 and 5
      years is 40% and 20% respectively. Based on these results, this new therapeutic
      approach is recommended as the treatment of choice in these unfortunate patients.
      The limits of the treatment of advanced colorectal cancer are also discussed.

PMID- 16420878
TI  - [Distal pancreatectomy: one technique with several indications].
AB  - INTRODUCTION: Distal pancreatectomy (DP) is performed for various pancreatic
      processes. This procedure has become less frequent since it ceased to be
      systematically used in oncologic gastric surgery and it is now performed mainly
      in patients with chronic pancreatitis. We present a series of patients who
      underwent DP and discuss technical features and surgical indications. PATIENTS
      AND METHODS: We performed a retrospective study of patients who underwent
      classical DP with associated splenectomy (CIE: 52.52) in our service from 1998
      2003. Fourteen DP were performed during the study period. RESULTS: The mean age
      was 52.6 years. Thirty-six percent of the patients were male (5/14). Diagnosis
      was mucinous cystic tumor of the pancreas (5), neuroendocrine tumor (3), focal
      chronic pancreatitis (2), pancreatic cancer (2), pancreatic injury due to a sharp
      instrument wound (1), and pancreatic metastases from renal cancer (1). The most
      frequently used diagnostic procedure was abdominal computerized axial tomography
      (13/14). Surgery was elective in 86%. The technique used to close the distal
      stump was manual suture (29%), mechanical stapling (64%) and suture plus stapling
      (7%). No statistically significant relationship was observed between closure of
      the stump and the development of pancreatic fistula. Morbidity was 35% and
      mortality was 0%. The mean length of hospital stay was 18 days. CONCLUSIONS: DP
      can be performed without mortality but morbidity is not inconsiderable and is
      usually associated with the development of pancreatic fistulas. The indications
      for DP have changed and currently this procedure is performed for several
      pancreatic processes that are becoming increasingly frequent.

PMID- 16420879
TI  - [Endosonographic and manometric assessment of the internal anal sphincter in
      patients with chronic anal fissure].
AB  - INTRODUCTION: High anal resting pressures have been implicated in the
      pathophysiology of chronic anal fissure. It is not known, however, whether
      altered function is associated with any morphological abnormalities of the
      internal anal sphincter (IAS). The aims of the present study were to determine
      IAS thickness in patients with chronic anal fissure and to investigate the
      correlation between IAS thickness and anal resting pressure. PATIENTS AND METHOD:
      Patients with chronic anal fissure were prospectively included between November
      1999 and December 2002. Patients with a history of inflammatory bowel disease,
      anal surgery, and those previously treated with nitroglycerine ointment or
      botulinum toxin were excluded. Anal endosonography and manometry were performed.
      IAS thickness was considered to be increased when it was > 2.5 mm in patients <
      50 years and > 3 mm in patients > or = 50 years. Anal resting pressure was
      considered to be increased when it was higher than 80 mmHg. RESULTS: Sixty-three
      patients were analyzed. An abnormally thick IAS was observed in 58 patients
      (92%). The mean IAS thickness was 3.7 +/- 0.7 mm. IAS hypertonia was found in 47
      patients (66%). The mean anal resting pressure was 91 +/- 28 mmHg. No correlation
      was found between IAS thickness and anal resting pressure (r = 0.05; p < 0.68).
      CONCLUSIONS: Most of the patients with chronic anal fissure had an abnormally
      thick IAS. However, increased thickness of the IAS did not correlate with
      increased anal resting pressure.

PMID- 16420880
TI  - [Quality of life after laparoscopic fundoplication for gastroesophageal reflux
      disease].
AB  - OBJECTIVE: To evaluate our results in terms of satisfaction and quality of life
      in patients who underwent laparoscopic 360 degrees fundoplication for
      gastroesophageal reflux disease. PATIENTS AND METHOD: We performed a cross
      sectional study of 49 consecutive patients who underwent laparoscopic 360 degrees
      fundoplication for gastroesophageal reflux disease. All patients had been
      operated on more than 6 months previously by the same surgeon. Postoperative
      morbidity was recorded. Patients were sent the SF-36 and GIQLI quality of life
      questionnaires and were also asked about their degree of satisfaction with the
      surgery. RESULTS: The mean age was 40.5 years (range, 23-71). There were nine
      women and 40 men. All patients underwent a floppy 360 degrees fundoplication and
      crural closure. There were no conversions. The complication rate was 8.2% (one
      case each of fever of unknown origin, acute urinary retention, self-limiting
      bleeding and hernia from a port). Forty-three patients completed the
      questionnaires (87.7%). Satisfaction with surgery was 8.7 points (out of 10),
      89.5% would undergo surgery again and 94.6% would recommend it to a relative. The
      results of the SF-36 questionnaire were similar to population-based reference
      values except in the domains of physical functioning and bodily pain where
      statistically significant differences were found. The mean global GIQLI score was
      110.8, which was similar to other studies published in the medical literature.
      CONCLUSIONS: Although this is a cross-sectional study, these preliminary results
      indicate a high degree of satisfaction with laparoscopic fundoplication, which
      was reflected in the results of the quality of life questionnaires.

PMID- 16420881
TI  - [Radio-guided occult lesion localization combined with sentinel node biopsy in
      women with breast cancer].
AB  - INTRODUCTION: The practice of intratumoral radiocolloid injection for sentinel
      node biopsy (SNB) allows localization of nonpalpable breast tumors in the same
      surgical intervention, using the technique known as radio-guided occult lesion
      localization (ROLL). PATIENTS AND METHOD: We present our experience with the
      combined use of both techniques (SNB and ROLL). A total of 233 patients were
      retrospectively analyzed: 65 patients underwent ROLL and 168 patients underwent
      wire-guided localization (control group) as the excision modality. Both groups
      had comparable pathologic and radiologic features. RESULTS: Complete excision of
      the lesion was achieved at the first attempt in only 169 patients. There were no
      significant differences among groups in surgical margin status (margins were
      adequate in 80% of ROLL patients vs 69.9% of non-ROLL patients) or in maximum
      specimen diameter (6.85 cm vs 6.52 cm, respectively). CONCLUSION: We conclude
      that ROLL is an acceptable alternative to wire-guided localization in patients
      with nonpalpable breast tumors undergoing SNB, leading to easier lesion excision
      and greater patient comfort.

PMID- 16420882
TI  - [Presentation and outcome of incarcerated external hernias in adults].
AB  - OBJECTIVE: The aim of this study was to determine the clinical presentation and
      outcome of incarcerated external hernias in adults, as well as to identify the
      factors that might have some influence on outcome. PATIENTS AND METHOD: A
      retrospective study of 230 adult patients who underwent emergency surgical repair
      of incarcerated external hernias from 1992 to 2001 was performed. The
      characteristics of clinical presentation, type of anesthesia, surgical
      procedures, complications and mortality were studied. To determine clinical
      factors that might have some influence on outcome, an univariate analysis was
      also performed. RESULTS: There were 77 femoral hernias, 70 inguinal, 43 umbilical
      and 40 incisional hernias. Seventy-four patients (32.2%) presented after 48 h of
      symptom onset. Significant associated diseases were found in 135 patients
      (58.7%). General anesthesia was used in 140 patients (60.9%), spinal anesthesia
      in 86 patients and local anesthesia in four patients. The most commonly used
      procedures were anatomic repair and tension-free hernioplasty. Bowel resection
      was required in 31 patients (13.5%). Overall and major morbidity and mortality
      were 37.8%, 10% and 3.9%, respectively. Factors that were significantly
      associated with unfavorable outcome were longer duration of symptoms, late
      hospitalization, concomitant diseases, and a high ASA class. CONCLUSIONS:
      External hernias produce elevated morbidity and mortality if treatment is
      undertaken as an emergency. Thus, early diagnosis and elective repair of
      uncomplicated hernias should be performed in adults.

PMID- 16420883
TI  - [Colon cancer: a rare complication in a colonic esophageal segment after
      coloesophagoplasty].
AB  - We report the case of a 65-year-old woman who presented to the Hermanos
      Ameijeiras Hospital in Cuba due to dysphagia for the previous 5 months. Forty
      years previously, she had undergone esophagocoloplasty for caustic esophagitis.
      Adenocarcinoma was diagnosed in the colonic interposition. The tumor was resected
      with oncologic margins and food transit was successfully restored.

PMID- 16420884
TI  - [Intestinal hemangiopericytoma].
AB  - A case of intestinal hemangiopericytoma is described. This localization is
      extremely rare. Clinical presentation consisted of upper digestive hemorrhage and
      abdominal mass; 9 months after surgical removal, the patient presented a single
      liver metastasis located in the left lobe, which was resected. Twenty-one months
      after the first surgical procedure the patient shows a favorable outcome. We
      review the literature and discuss this exceptional form of hemangiopericytoma, as
      well as its outcome.

PMID- 16420886
TI  - [Moderately differentiated adenocarcinoma of the gall bladder].

PMID- 16420885
TI  - [Acute cholecystitis secondary to recurrent cholelithiasis after subtotal
      cholecystectomy].
AB  - Subtotal cholecystectomy is a well-established procedure for complicated acute
      cholecystitis. Short-term safety is good and few complications have been
      described during follow-up. However, residual gallbladder mucosa can produce new
      calculi, which can provoke the same symptoms and complications as those in non
      operated patients and which require a high index of suspicion. Surgical treatment
      can be indicated. We report the case of a man who underwent subtotal
      cholecystectomy for complicated cholecystitis. Postoperative follow-up did not
      reveal residual cholelithiasis. The patient developed obstructive jaundice 8
      years later. Initial studies (computed tomography and ultrasonography) showed no
      complications. Endoscopic retrograde cholangiopancreatography revealed residual
      gallbladder with recurrent cholelithiasis. Conservative management was initiated
      but gallbladder stump cholecystectomy was required for acute cholecystitis.

PMID- 16420887
TI  - [Current status of minimally-invasive surgery in the treatment of malignant
      tumors of the esophagus and cardia].

PMID- 16420888
TI  - [Informing the surgical patient. Reflections on the basic law of patient
      autonomy].
AB  - The basic law of patient autonomy represents a new point of reference for
      surgeons in terms of their obligation to inform the patient and obtain consent.
      The main contribution of this new law is its explicit recognition of the patients
      autonomy in decision-making in medicine, leading to new obligations among health
      professionals in matters of information and consent. Nevertheless, because of the
      special characteristics of surgery, these legal principles need to be
      contextualized within the reality of surgical practice in order to harmonize
      rights, obligations and ethical values. In light of this new law, the present
      article aims to provide a reflection on the complexities of providing information
      in surgical practice with a view to identifying areas of conflict and making
      recommendations for their resolution.

PMID- 16420889
TI  - [Application of the EUSOMA criteria in breast units in countries of the European
      Union].
AB  - All the countries of the European Union face similar challenges when providing
      adequate and high quality treatment in oncology. A working party was established
      to consider what should comprise a specialist service and the Requirements of a
      Breast Unit, published in 2000, represent the opinion of the European Society of
      Mastology (EUSOMA) on the standards required for creating high quality Breast
      Cancer Units across Europe. We studied the application of the mandatory
      requisites and general recommendations of EUSOMA: critical mass, or minimum
      number of patients, core team (composition and specific training), quality
      assurance, and application of diagnostic and treatment protocols. A thorough
      literature search was performed and was completed with information from search
      tools, the web pages of scientific societies, national associations for the fight
      against cancer, and health ministries of the countries belonging to the European
      Union. We also analyzed the latest reports of the European Parliamentary
      Committee for breast cancer. Distinct approaches to the multidisciplinary
      management of breast disease can be found in the United Kingdom, Sweden, Italy,
      France and Spain. A common European standard would be useful to improve the care
      provided to patients.

PMID- 16420890
TI  - [Laparoscopic surgery in cancer of the esophagus].
AB  - INTRODUCTION: For the last year we have substituted laparotomy with laparoscopy
      for the abdominal stage of esophageal cancer surgery. We report our experience of
      the introduction of video-assisted surgery in the treatment of esophageal cancer.
      PATIENTS AND METHOD: We report our experience of nine patients diagnosed with
      esophageal cancer. In seven patients laparoscopy was preceded by right
      thoracotomy and esophageal dissection. Then, a left anterolateral cervicotomy was
      performed to remove the specimen and to construct the esophagogastroanastomosis.
      In two patients the laparoscopic technique was performed first and the Ivor Lewis
      procedure was completed by right thoracotomy. RESULTS: Due to the reduced number
      of operated patients, the results are of little significance. Morbidity was
      38.3%. The mean duration of the surgical procedure in laparoscopic patients was 4
      h 50 min. However, perioperative blood loss, postoperative complications,
      analgesic requirements and mean length of hospital stay were reduced.
      CONCLUSIONS: Video-assisted esophagectomy can be performed as safely as
      conventional esophagectomy and has considerable perioperative advantages. The
      introduction of the laparoscopic procedure is the first step in using video
      assisted surgery at all stages of esophageal cancer surgery.

PMID- 16420891
TI  - [Repair of primary inguinal hernia: Lichtenstein versus Shouldice techniques.
      Prospective randomized study of pain and hospital costs].
AB  - INTRODUCTION: Hernia is one of the most widely studied processes, and the search
      for excellence has become the final aim. However, many controversies remain to be
      resolved. The objective of the present study was to analyze postoperative pain
      and costs using two techniques of primary inguinal hernia repair. PATIENTS AND
      METHOD: We performed a prospective, randomized study of 54 patients who underwent
      surgical repair of inguinal hernia through either the Lichtenstein or the
      Shouldice technique between June 2001 and May 2002. The following variables were
      analyzed: age, location and type of hernia, evaluation of tolerance to local
      anesthesia, surgical technique, operating time, pain at days 1, 3 and 5 after
      surgery, analgesic consumption, days until driving could be resumed, days off
      work, and occupation. RESULTS: The patient groups were similar, with no
      significant differences in age, location or type of hernia. For Lichtenstein
      hernioplasty, operating time was lower (p < 0.01); pain evaluation showed no
      significant differences on days 1 and 3 after surgery but was higher on day 5 (p
      = 0.064). No significant differences were found in analgesic consumption, time
      before driving could be resumed, or days off work. Freelance patients returned to
      work earlier, independently of the surgical technique performed. The cost of the
      Lichtenstein technique was 235 euros compared with 180 euros for the Shouldice
      technique and this difference was statistically significant (p < 0.05).
      CONCLUSION: In the hands of expert surgeons, the Shouldice technique is the
      procedure of choice in the repair of primary hernias. The results are just as
      satisfactory as those obtained with Lichtenstein hernioplasty and hospital costs
      are lower.

PMID- 16420892
TI  - [Multivariate study of risk factors for developing complications after
      multinodular goiter surgery].
AB  - INTRODUCTION: Multinodular goiter (MG) accounts for a large volume of procedures
      performed in endocrine surgery departments. However, risk factors for
      postoperative complications have not been systematically investigated. The aim of
      the present study was to evaluate surgical outcomes in terms of morbidity and
      mortality through multivariate statistical analysis with a view to determining
      risk factors in MG surgery. PATIENTS AND METHOD: A total of 672 patients who
      underwent surgery for MG were retrospectively reviewed. The variables analyzed
      were age, sex, prior surgery, disease duration, symptomatology, intrathoracic
      component, the surgeons experience, surgical technique, identification of
      structures, associated thyroid carcinoma and thyroid specimen weight. The chi
      squared test, Students t-test and logistic regression analysis were performed.
      RESULTS: Morbidity was 22% (n = 147) and mostly corresponded to
      hypoparathyroidisms and transitory recurrent lesions. Risk factors for developing
      these complications were symptomatic disease (p = 0.0131), hyperthyroidism (p =
      0.0333), compressive symptoms (p = 0.0158), clinical grade of the goiter (p =
      0.0482), surgical technique (p < 0.00001) and thyroid weight (p = 0.0302).
      Independent risk factors were surgical technique, hyperthyroidism and goiter
      grade. The definitive complication rate was 2.2% (n = 15), corresponding to six
      hypoparathyroidisms (0.9%) and 10 recurrent lesions (1.5%). The risk factor for
      their development was hyperthyroidism (p = 0.0037; RR = 2.8). CONCLUSIONS: The
      main independent risk factor for complications after MG surgery is
      hyperthyroidism.

PMID- 16420893
TI  - [Evaluation of a clinical pathway for laparoscopic cholecystectomy].
AB  - INTRODUCTION: Clinical pathways are standardized plans for the integral care of
      specific processes. In March 2002, a clinical pathway for laparoscopic
      cholecystectomy was introduced in our service. The aim of the present study was
      to evaluate this pathway 1 year after its implementation. METHODOLOGY: All
      patients included in the clinical pathway since its introduction were studied.
      Evaluation criteria included compliance, indicators of the effectiveness of
      clinical care, economic impact and indicators of satisfaction based on a survey.
      The results were compared with those in a series of patients who underwent
      surgery in the year before the introduction of the clinical pathway. Our hospital
      uses analytical accounting and the mean cost per process before and after the
      introduction of the clinical pathway was analyzed. RESULTS: A series of 160
      consecutive patients who underwent surgery during the year prior to the creation
      of the clinical pathway and who fulfilled the accepted inclusion criteria was
      evaluated. The mean length of hospital stay was 3.27 days. The mean cost per
      process before the introduction of the pathway was 2149 (+/- 768) euros. During
      the first year after the introduction of the pathway, 140 patients were included
      with an inclusion rate of 100%. The mean length of hospital stay in patients
      included in the clinical pathway was 2.2 days. The degree of compliance with
      length of hospital stay was 66.7%. The most frequent causes of breach were staff
      related, followed by patient-related (oral intolerance, pain, etc.). The mean
      cost in patients included in the clinical pathway was 1845 (+/- 618) euros.
      CONCLUSIONS: Laparoscopic cholecystectomy is a suitable process with which to
      initiate systematization of clinical pathways. The results show that length of
      hospital stay has been significantly reduced without increasing morbidity.
      Patient satisfaction has been high.

PMID- 16420894
TI  - [Fissure-in-ano. Alterations in continence and quality of life during disease and
      at six months after lateral subcutaneous internal sphincterotomy].
AB  - OBJECTIVE: To prospectively evaluate alterations in continence and quality of
      life produced by lateral internal sphincterotomy with each patient acting as his
      or her own control. PATIENTS AND METHOD: Quality of life (SF-36 questionnaire)
      and fecal incontinence (Cleveland Clinic Florida-Fecal Incontinence [CCF-FI]
      questionnaire) were evaluated before and 6 months after lateral internal
      sphincterotomy was performed in 113 consecutive patients diagnosed with chronic
      anal fissure. RESULTS: Four patients were excluded because of their inability to
      complete the SF-36 questionnaire without help. Of the 109 remaining patients,
      there was persistence or relapse of anal fissure in six (5.5%). One patient
      refused to complete the quality of life questionnaire again and was excluded from
      the study. Of the 108 patients who completed the study, the median (interquartile
      range) score in the CCF-FI scale increased from 0.00 (3) before the intervention
      to 1(4) in the postoperative period (p = 0.001). Quality of life significantly
      improved after the operation, since the scores of the following scales increased:
      physical functioning (p = 0,005), role limitations-physical (p = 0.006), bodily
      pain (p < 0.001), vitality (p = 0.008), social functioning (p = 0.022) and mental
      health (p < 0.001). No statistically significant differences were found in
      general health perception or in role limitations-emotional. CONCLUSION: Despite
      deterioration in continence, sphincterotomy improves quality of life in patients
      with anal fissure.

PMID- 16420895
TI  - [Diverticular disease of the cecal appendix].
AB  - INTRODUCTION: Appendiceal diverticula are uncommon, with an incidence of less
      than 1% in surgical specimens. We report a series of 14 patients with
      diverticular disease of the cecal appendix. PATIENTS AND METHOD: A total of 547
      patients with a clinical diagnosis of acute appendicitis underwent surgery over 4
      years. Of these, 11 patients showed acute appendiceal diverticulitis at
      histological examination, and three patients showed diverticulosis associated
      with appendicitis. Clinical features were compared between the group of patients
      with diverticular disease and the group with acute appendicitis. Statistical
      analysis was performed using Students t-test and the chi-squared test. RESULTS:
      The overall incidence of appendiceal diverticula was 2.6%, and 2% of cases had
      acute diverticulitis. In the group with diverticular disease, the mean age and
      the percentage of patients under clinical observation before the decision to
      perform surgery was made were significantly higher. There was a nonsignificant
      predominance of male over female patients and no differences were found in mean
      white cell count. No radiological investigations were performed in the
      diverticular group. CONCLUSIONS: The incidence of appendiceal diverticula was
      much higher in our series than that reported in the literature. We found no
      clinical or perioperative data that would serve to differentiate acute
      diverticulitis from acute appendicitis.

PMID- 16420896
TI  - [Liposarcomas of the mediastinum in atypical locations: report of two cases].
AB  - Liposarcomas of the mediastinum are unusual tumors characterized by compression
      of neighboring structures and frequent recurrence. Computed tomography and
      magnetic resonance imaging provide useful data for diagnosis. According to a
      review of the literature, surgical resection is the most effective treatment. We
      report two cases of mediastinal liposarcoma: the first was a liposarcoma that was
      a recurrence of an atypical lipoma of the neck, and the second was a giant
      mediastinal liposarcoma involving both hemithoraces.

PMID- 16420898
TI  - [Traumatic diaphragmatic rupture].
AB  - Traumatic diaphragmatic rupture is an infrequent lesion that can result from
      penetrating or blunt trauma to the abdomen or chest. Early diagnosis continues to
      be a challenge and this type of injury is associated with high morbidity and
      mortality. Preoperative diagnosis is difficult and a high level of suspicion,
      careful scrutiny of the chest x-ray, and early surgical treatment are required
      for successful management. We present a case of rupture of the left hemidiaphragm
      that was diagnosed and treated successfully within the first few hours. We also
      review the literature on controversial issues in the diagnosis and treatment of
      this injury.

PMID- 16420897
TI  - [Small bowel obstruction due to metastatic lobular carcinoma of the breast].
AB  - Although breast cancer most frequently metastasizes to the bone, lung, pleura,
      liver, adrenal glands and brain, it can also affect other organs such as the
      small bowel and ovaries, especially if the type of cancer is infiltrating and
      lobular. We present a case of metastases to the small bowel and ovaries from
      pleomorphic type infiltrating lobular breast carcinoma presenting as intestinal
      obstruction. Barium transit study revealed a stenosis in the jejunum and another
      in the terminal ileum at the ileocecal valve area. A flat formation in the area
      of the ileocecal valve was observed on endoscopy but the results of biopsy were
      negative, a fairly frequent finding due to the absence of infiltration of the
      intestinal mucosa. Pathological and immunohistochemical study of the intestinal
      and ovarian surgical specimens confirmed the diagnosis of metastases from lobular
      carcinoma of the breast, which was corroborated by breast biopsy.

PMID- 16420899
TI  - [Image of the month. Splenic injury].

PMID- 16420900
TI  - [Positron emission tomography/computed tomography (PET/CT): present and future of
      a new imaging technique in oncology].

PMID- 16420901
TI  - [Abdominal wall closure in laparotomy].
AB  - The midline laparotomy is among the most common ways of accessing the peritoneal
      cavity. This approach is not only used for surgery of the digestive tract but is
      also extensively applied in vascular, gynecology and urological surgery. When
      this surgical procedure is conducted in an emergency setting, and depending on
      the type of surgery (clean and /or contaminated), the incidence of complications
      may be particularly high, especially when acute dehiscence of the wall occurs
      (evisceration). Furthermore, the rate of herniation related to midline laparotomy
      is still high at approximately 16% of cases. Despite efforts to evaluate
      different suture techniques, suture threads (reabsorbable or non-reabsorbable)
      and general factors that may interfere with the repair process, the incidence of
      complications associated with this approach has not been reduced. After multiple
      studies including meta-analyses, the outcome of laparotomy closure has not
      essentially improved. We should therefore consider the use of new ways of closing
      the abdomen in selected patients that might somehow reinforce the surgical wound
      and notably reduce the incidence of short- and medium-term complications. One
      such method could perhaps be the use of a biomaterial to support and strengthen
      conventional sutures.

PMID- 16420902
TI  - [The surgery that I have lived (1932-1988)].

PMID- 16420903
TI  - [Results and prognostic factors in the Hartmann procedure].
AB  - INTRODUCTION: The introduction of one-stage procedures in emergency colonic
      surgery many years ago has relegated the use of the Hartmann procedure to the
      most seriously-ill patients, which has led to the high morbidity and mortality
      rates associated with this surgical technique. The aim of our study was to
      investigate our results using Hartmanns procedure and to evaluate several
      prognostic factors of postoperative mortality in this group of patients. PATIENTS
      AND METHODS: From January 1995 to December 2000, 79 patients (34 men and 45
      women) with a mean age of 71.5 years underwent Hartmanns operation. Almost all
      the series (91.1%) had comorbidities. In this group of patients, morbidity and
      mortality were analyzed retrospectively, and a multivariate logistic regression
      analysis was performed to study prognostic factors of postoperative mortality.
      RESULTS: The indications for surgery were acute peritonitis (77.2%), intestinal
      obstruction (18.9%), and lower gastrointestinal hemorrhage (3.7%). The most
      frequent etiology was acute diverticulitis (36 patients), followed by complicated
      colorectal carcinoma (18 patients). In 70.9% of the patients (56 patients) one or
      more postoperative complications was observed. Reoperation was performed in 15
      patients (18.9%) and overall postoperative mortality was 45.5%. Renal failure
      (creatinine > or = 120 micromol/l) and high surgical ASA score (III or IV)
      reached statistical significance as predictive factors of mortality in these
      patients (p=.001 and p=.005, respectively). CONCLUSION: The patients who
      underwent Hartmanns procedure with high surgical ASA score and/or renal failure
      were at significantly higher risk of mortality.

PMID- 16420904
TI  - [What has changed in adrenalectomy? From open surgery to laparoscopy?].
AB  - INTRODUCTION: After the introduction of the laparoscopic approach in adrenal
      surgery, this technique has become the gold standard in surgical adrenal
      diseases. Nevertheless, comparative studies with open surgery are scarce and the
      impact of laparoscopic techniques on these diseases is unknown. OBJECTIVE: To
      evaluate our experience of adrenal surgery over a 14-year period, before and
      after the introduction of laparoscopic adrenalectomy, and to analyze the
      influence of this technique on the surgical management of adrenal diseases.
      PATIENTS AND METHOD: From January 1990 to June 2004, 78 patients underwent
      adrenalectomy. Between 1990 and 1998, open adrenalectomy was performed in 24
      patients, while between 1999 and 2004, 54 patients underwent the laparoscopic
      approach and 1 underwent open surgery. Data for the open group were
      retrospectively reviewed while those for the laparoscopic group were
      prospectively registered in the advanced laparoscopic surgery database of
      Hospital Sant Pau (HSP). RESULTS: The mean age was 47 years (16-75) in the open
      group and was 49 years (17-77) (p = NS) in the laparoscopic group. Distribution
      by surgical indication was similar in both periods concerning primary
      hyperaldosteronism, hypercortisolism, and pheochromocytoma, with a significant
      increase in surgical cases indicated by malignancy (1 vs 4) or incidentaloma (2
      vs 13) (p<.001). Operating time was reduced from 150 min (65-210) in the open
      group to 90 min (30-300) in the laparoscopic group (p<.01). Morbidity was also
      reduced (20% vs 6%, p<.01). The size of lesions resected by open or laparoscopic
      surgery (4 cm [0.4-16] vs 3.5 cm [1.2-14]) was similar. The mean length of
      hospital stay was reduced from 8 days (3-13) to 3 days (2-12) (p<.01). The number
      of adrenalectomies performed in HSP was 24 in the first period (1990-1997) vs 40
      in the second (1998-2004). This represented an increase from 3/year to 6.6/year
      mainly due to the increase in the number of incidentalomas. CONCLUSIONS: The
      laparoscopic approach has improved immediate surgical results (operating time,
      morbidity, and length of hospital stay). There was a clear increase in the number
      of adrenalectomies, and especially of incidentalomas, due to improved diagnostic
      techniques and the availability of a less aggressive approach.

PMID- 16420905
TI  - [Colorectal laparoscopy in the Canary Islands. A multicenter study of 144
      patients].
AB  - INTRODUCTION: To analyze the short-term results of laparoscopic colorectal
      surgery (LCRS) in the Canary Islands. MATERIAL AND METHODS: A questionnaire was
      sent to hospitals performing laparoscopy and retrospective data on demographic,
      perioperative and pathological variables in 144 patients who underwent LCRS
      between May 1993 and May 2003 were obtained. RESULTS: Sixty-five men and 79 women
      underwent colon (n=126) and rectal (n=18) surgery in the last 16 months of the
      study period. The most frequently performed procedure was sigmoidectomy in 85
      patients (59%). The most frequent diagnosis was colon adenocarcinoma in 73
      patients (50%), followed by diverticular disease in 36 patients (25%). The mean
      values of the variables studied were: body mass index, 27.3 (range, 22-35);
      operating time, 175 min (range, 60-255); blood loss, 183.6 ml (range, 50-500).
      Peristalsis reinitiated at 45 h; oral diet was introduced at 67 h and the overall
      mean length of hospital stay was 7.8 days (range, 3-30). The length of hospital
      stay was significantly longer in patients with complications (14.5 vs 6.4; p
      <.01). There were 7 conversions (4.86%). There were no perioperative deaths. The
      overall morbidity rate was 28%. The most frequent early complication was surgical
      wound infection in 9 patients (6.2%). Anastomotic leak was detected in 5 patients
      (3.4%). CONCLUSIONS: LCRS has been shown to be a safe and effective technique
      that has recently increased in the centers surveyed. The factor with the greatest
      influence on length of hospital stay was the development of postoperative
      complications.

PMID- 16420906
TI  - [Usefulness of absorbable meshes in the management of splenic trauma].
AB  - INTRODUCTION: The spleen is not an essential organ for survival but given its
      important role in immunologic functions its preservation is justified. OBJECTIVE:
      To analyze our experience with absorbable meshes applied to treat splenic
      injuries. PATIENTS AND METHOD: We performed an ambispective study. From July 1999
      to February 2004, 30 patients were treated for traumatic splenic injuries.
      Ultrasonography and/or spiral computed tomography scanning was carried out for
      the initial screening evaluation and grading of splenic injuries. The New Injury
      Severity Score (NISS) was calculated to quantify the severity of trauma.
      Operative splenic preservation was performed according to established selection
      criteria. Splenorrhaphy with prosthetic material was accomplished by means of a
      bag of polyglycolic acid mesh measuring 18 cm yen 23 cm (Dexon mesh) that was
      hand tailored and wrapped around the entire surface of the spleen. RESULTS:
      Thirty patients with splenic traumatic injuries were treated. The mean age was
      36.2 +/- 16.6 years. Twenty-three patients (76.6%) required splenectomy,
      nonoperative management was achieved in 1 patient (3.3%), and splenorrhaphy with
      prosthetic material was carried out in 6 patients (20%). Grade III injuries were
      present in 13 patients (43.3%), grade IV in 13 patients (43.3%), and grade V in 4
      patients (13.3%). The mean NISS was 18.9 +/- 9.1. No significant differences were
      detected between the two groups (splenectomy or mesh splenorrhaphy) in NISS
      (p=.53) or grade of splenic injuries (p=.69). Morbidity was related to the
      presence of multiple injuries (p=.002) and was greater in the group with mesh
      splenorrhaphy (p=.002); however, there were no septic complications in this
      group. A positive correlation was observed between the length of hospital stay
      and NISS (p=.01). The length of hospital stay was also significantly associated
      with the presence of multiple injuries (p=.005) and with morbidity (p=.0002), but
      was not associated with the type of surgery carried out (p=.17). No complications
      were observed during follow-up (median of 28 months) in patients who underwent
      splenic salvage procedures. CONCLUSIONS: Mesh splenorrhaphy is a suitable
      therapeutic option for patients with severe trauma, grade IV splenic injuries, or
      delayed rupture of the spleen. Both morbidity and length of hospital stay were
      associated with the presence of multiple injuries rather than with the type of
      surgery carried out. The safety, effectiveness and absence of septic
      complications related to the use of prosthetic material in splenic trauma salvage
      surgery were notable.

PMID- 16420907
TI  - [Initial experience in the laparoscopic repair of incisional/ventral hernias in
      an outpatient-short stay surgery unit].
AB  - INTRODUCTION: Hernia is a frequent complication in abdominal surgery. There are a
      multitude of repair techniques, ranging from classical direct closure of the
      defect and tension-free mesh repair using open surgery to the recent development
      of laparoscopic repair. OBJECTIVE: To evaluate the safety and effectiveness of
      laparoscopic repair of incisional/ventral hernias and its applicability in an
      outpatient-short stay surgical unit. PATIENTS AND METHOD: We performed a
      prospective study of 135 consecutive patients. All patients had incisional (132
      patients) or ventral hernias (2 patients) that were laparoscopically repaired
      between February 1999 and July 2003. The parameters analyzed were the number of
      prior abdominal interventions and hernia repairs, the number of defects, their
      location, operating time, type of mesh, postoperative complications,
      postoperative length of hospital stay, and recurrence rate during a mean follow
      up period of 12 months. RESULTS: Of the 135 patients, 16 (11.8%) underwent
      conversion to open surgery. The most frequent location of the defect was
      infraumbilical. Of the 119 patients who underwent laparoscopic repair, more than
      one hernia was found in 67. The mean operating time was 72.3 +/- 28.3 min. The
      most frequent immediate complication was seroma in the hernia sac. A total of
      92.4% of the patients were discharged within 24 h of the intervention. The
      recurrence rate was 5.04%. CONCLUSION: Laparoscopic repair of incisional/ventral
      hernias is a safe method that allows outpatient management of this defect.
      Moreover, the technique presents the advantages of minimally invasive surgery,
      allowing clear identification of multiple hernial defects, with an acceptable
      percentage of complications and low recurrence rate.

PMID- 16420908
TI  - [Laparoscopic repair of secondary lumbar hernias: open vs. laparoscopic surgery.
      A prospective, nonrandomized study].
AB  - INTRODUCTION: Lumbar hernia is an uncommon defect of the posterior abdominal wall
      and its surgical treatment remains controversial. The aim of the present study
      was to evaluate the utility of laparoscopy versus open surgery. PATIENTS AND
      METHOD: We performed a prospective, nonrandomized study of 16 patients with
      secondary lumbar hernias who underwent surgery between January 1997 and January
      2003. Nine patients underwent laparoscopy and 7 underwent open surgery. The
      variables analyzed were clinical features, hospital data (operating time and
      length of hospital stay), patient comfort (analgesic consumption and return to
      normal daily activity) and recurrences. Hospital costs were also analyzed.
      RESULTS: No differences were found between the two groups in age or history,
      although the size of laparoscopically-repaired defects was smaller. Mean
      operating time, postoperative morbidity, mean length of hospital stay, analgesic
      consumption, and return to daily activities were significantly lower in the
      laparoscopic group (P<.01). No statistically significant differences in the cost
      of the process were found according to surgical approach but significant
      differences were found in final cost after including the cost of readmissions and
      recurrences (P<.01). CONCLUSIONS: In our series, the laparoscopic approach was
      more effective than traditional open surgery in the repair of secondary lumbar
      hernias while the cost of the two procedures was the same.

PMID- 16420909
TI  - [Jaundice and chronic pancreatitis: common bile duct compression by pancreatic
      pseudocyst].
AB  - In chronic pancreatitis, obstructive jaundice solely due to common bile duct
      compression by a pancreatic pseudocyst is highly unusual. In most of these cases,
      the jaundice is due to fibrotic stricture of the intrapancreatic portion of the
      common bile duct. We report two cases of obstructive jaundice in chronic
      pancreatitis with pseudocyst. Operative findings and follow-up during the
      postoperative period demonstrated compression by the pseudocyst over the common
      bile duct as the only etiologic factor of the jaundice. We believe that
      intraoperative cholangiography should be performed after drainage of a pseudocyst
      to correctly assess the etiology of obstruction.

PMID- 16420910
TI  - [Extra-adrenal pheochromocytoma: update of the most controversial features.
      Apropos of two cases].
AB  - Pheochromocytomas are uncommon neuroendocrine tumors. They are usually
      symptomatic and sporadic and are generally located in the adrenal medulla. We
      present two cases of extra-adrenal nonfunctional pheochromocytomas located in the
      retroperitoneum. The tumors were apparently benign and sporadic and were not
      associated with other neoplasms or hereditary diseases. Ultrasonography, computed
      axial tomography and magnetic resonance imaging were performed before complete
      excision of the tumors using open abdominal surgery. Several immunohistochemical
      techniques were performed to reach the definitive diagnosis. After 8 and 14
      months of follow-up, there is no evidence of recurrence or other syndromes. As a
      consequence of these two cases, we performed a review of the literature on the
      topic, focussing on the most controversial areas.

PMID- 16420912
TI  - [Image of the month].

PMID- 16420911
TI  - [Prosthetic replacement of the inferior vena cava. Current controversies].
AB  - A ringed polytetrafluoroethylene (PTFE) graft is currently the most widely used
      replacement for the inferior vena cava, although clinical studies comparing this
      technique with non-ringed prostheses are lacking. There is no consensus on the
      need to use an anticoagulant or associate a temporary distal arteriovenous
      fistula to increase venous flow. At present, the best therapeutic strategy cannot
      be determined. We present a case of retroperitoneal sarcoma infiltrating the
      infrarenal vena cava, right colon and ureter that was surgically treated in our
      hospital. En bloc resection was performed and the vena cava was reconstructed
      using a non-ringed PTFE graft associated with systemic anticoagulation.

PMID- 16420914
TI  - [The laparoscopic approach in inguinal hernia: a single technique and tactical
      resource].

PMID- 16420913
TI  - [Giant retroperitoneal cyst].

PMID- 16420915
TI  - [Cervicoscopy].
AB  - The beginning of cervicoscopy dates back to the first laparoscopic
      parathyroidectomy in 1996. This operation, with its distinct variants, has today
      become a valid therapeutic option in many well-regarded centers. Later on
      endoscopic or video-assisted thyroidectomy was introduced, despite the limits
      imposed by the large size of the gland on its removal. Consequently, this
      technique is indicated in a small number of patients but both parathyroidectomy
      and thyroidectomy provide significant advantages over conventional surgery, which
      have been demonstrated in prospective studies. The main advantages are a better
      cosmetic outcome and a less distressing postoperative course. Both approaches
      have been proved to be safe and feasible in any surgical background and their
      complication rate is similar to that of traditional open surgery of the neck.
      Videoscopic access to neck lymph nodes (central and lateral compartments) seems
      to be highly promising, whereas other fields of application such as carotid
      artery surgery and spine surgery are still the object of experimental studies.
      Consequently, cervicoscopy should be considered an important surgical tool which
      already shows great possibilities but which could be further improved.

PMID- 16420916
TI  - [The required coordination of pancreas-islet-kidney transplantation in Spain].
AB  - We describe the historical background and current situation of pancreatic and
      islet cell transplantations in Spain and other countries, as well as their
      relationship with replacement therapy in chronic renal failure in diabetic kidney
      transplant recipients. Emphasis is placed on the improved results achieved in the
      last decade, the increased demand for these techniques and the need for highly
      efficient organization of these transplantations to optimize the available
      resources, which are clearly limited in terms of both donation and finances. The
      process initiated by the National Transplantation Organization (NTO) to
      coordinate all these activities and the preparation of a consensus document
      endorsed by all the professional bodies involved is described.

PMID- 16420917
TI  - [National project for the management of clinical processes. Surgical treatment of
      inguinal hernia].
AB  - INTRODUCTION: The high prevalence of surgical treatment for inguinal hernia
      (especially in general surgery) prompted the Spanish Association of Surgeons to
      perform a national study to identify the most important indicators. OBJECTIVE: To
      analyze healthcare quality in elective surgery for inguinal hernia by evaluating
      scientific-technical quality, efficiency, effectiveness, and patient
      satisfaction. MATERIAL AND METHODS: A prospective, longitudinal, descriptive
      study from diagnosis to postoperative follow-up was performed. Patients who
      underwent surgery for unilateral or bilateral, primary or recurrent inguinal
      hernias were included. Exclusion criteria were emergency surgery and associated
      surgical procedures. Clinical indicators were selected after a literature review.
      RESULTS: Forty-six hospitals corresponding to 16 Autonomous Communities with a
      total of 386 patients participated in this study. The mean follow-up was 18
      months. The mean age of the patients was 56.33 years and 88.3% were male. Half
      the patients (50.1%) were American Society of Anesthesiologists (ASA) grade I. A
      total of 95.6% did not comply with the protocol for preoperative tests of the
      Spanish Association of Surgeons. Antibiotic prophylaxis was used in 75.39% and
      thromboembolic prophylaxis was used in 40.04%. Ambulatory surgery was performed
      in 33.6%. Local anesthesia and sedation only were used in 16.36% of the patients.
      The most frequently used surgical procedures involved mesh repair (Lichtenstein
      50%, Rutkow-Robbins 17.1%), laparoscopy was used in 5.2% of the patients, and the
      Shouldice technique was used in 8.5%. The mean length of hospital stay was 47.5
      hours in inpatients and was 11.65 hours in patients who underwent ambulatory
      surgery. Notable among the complications was hematoma in 11.6%. Ninety-six
      percent of the patients were satisfied or highly satisfied. The most highly
      scored items in the satisfaction survey were those related to information,
      personal dealings with staff, and the staffs kindness. The lowest scored items
      dealt with punctuality and accessibility. Follow-up at 18 months showed a
      recurrence rate of 4.11% with a total recovery time estimated by patients of 7.26
      weeks. CONCLUSIONS: Analysis of the process revealed areas for improvement and
      strong points. Strong points consisted of up-to-date choice of surgical
      technique. The most frequently used techniques were tension-free procedures and
      the Shouldice technique. The following areas for improvement were identified:
      adherence to protocols for preoperative evaluation, increased use of ambulatory
      surgery, local anesthesia and sedation, appropriate use of antibiotic and
      thromboembolic prophylaxis in selected patients and a reduction in the length of
      hospital stay in inpatients. Patient satisfaction with the treatment was
      acceptable.

PMID- 16420918
TI  - [Influence of preoperative biliary drainage on postoperative morbidity and
      mortality after pancreatoduodenectomy].
AB  - Pancreatoduodenectomy is the only potentially curative treatment for
      peripapillary tumors. However, postoperative mortality remains as high as 5% and
      as many as 50% of patients have postoperative morbidity. Preoperative endoscopic
      retrograde cholangiopancreatography and placement of a biliary drainage stent aim
      to achieve a precise diagnosis, reduce jaundice and improve the results of
      surgery for biliary malignancies, but the effectiveness of preoperative biliary
      drainage in the prevention of postoperative infections is controversial. A
      retrospective analysis was performed in a series of 58 patients with
      periampullary tumors who underwent pancreatoduodenectomy and the relationship
      between preoperative biliary drainage and postoperative complications was
      examined. Biliary drainage (25.8%) before pancreatoduodenectomy was significantly
      associated with more frequent biliary and pancreatic anastomotic leakage (60%
      with drainage versus 20.9% without drainage), higher postoperative morbidity, and
      greater mean postoperative length of hospital stay (33.3 days with drainage
      versus 21.6 without drainage). No significant difference was found between the
      two groups in postoperative mortality at 30 days (13.7%). The effectiveness of
      biliary drainage before surgery in patients with pancreatic and peripancreatic
      lesions has not been well established, but we believe that this procedure should
      be avoided whenever possible in patients with potentially resectable pancreatic
      and peripancreatic lesions. Prospective randomized studies are required to
      clarify the indications for preoperative biliary drainage in these patients.

PMID- 16420919
TI  - [Duodenal adenocarcinoma].
AB  - INTRODUCTION: Duodenal adenocarcinoma is an infrequent neoplasm. Consequently,
      there are no large series that would allow conclusions to be reached on its
      diagnosis and treatment. PATIENTS AND METHOD: A retrospective study (1999-2003)
      of five patients diagnosed with duodenal adenocarcinoma in our service was
      performed. RESULTS: The mean age was 54 years. Eighty percent were male. All
      patients showed weight loss and abdominal pain. The tumors were localized in the
      second portion in three patients and in the third portion in two patients. All
      patients underwent gastrointestinal endoscopy with biopsy, which revealed
      adenocarcinoma. The most effective diagnostic test was computed tomography. In
      all patients, the preoperative diagnosis was correct. The technique performed was
      cephalic duodenopancreatectomy in three patients and duodenectomy with atypical
      pancreatic resection and right hemicolectomy in one patient. A decision not to
      perform surgery was made in one patient with liver metastases. Two patients who
      underwent surgery showed no complications. The remaining two patients showed slow
      gastric emptying in one patient and pancreatitis of the stump leading to fatal
      systemic inflammatory response syndrome in the other. Patient survival was 60, 13
      and 1 month respectively. There were no recurrences. The patient who did not
      undergo surgery died at 4 months. CONCLUSION: Duodenal adenocarcinoma is an
      infrequent tumor that is associated with various diseases. Surgical treatment is
      usually cephalic duodenopancreatectomy. Survival in resected patients is better
      than that obtained in primary pancreatic tumors.

PMID- 16420920
TI  - [Variation in the prognostic value of p53 protein in relation to tumoral stage in
      patients with colorectal adenocarcinoma].
AB  - OBJECTIVE: To analyze the prognostic value of p53 protein as a marker of
      recurrence risk in each tumoral stage. PATIENTS AND METHOD: A prospective study
      of a cohort of 288 patients who underwent surgery for colorectal adenocarcinoma
      was performed. Stage 1 of the tumor-node-metastasis (TNM) classification was
      found in 42 patients (14.6%), stage II in 144 (50%) and stage III in 102 (35.4%).
      Histopathological variables were examined in tumor samples fixed in formol and
      embedded in paraffin and p53 (DO7 antibody) and proliferative cell nuclear
      antigen (PC-10 antibody) proteins were determined using immunohistochemistry. The
      results of p53 were analyzed in each of the categories of clinical and
      histopathological variables. Recurrence-free survival was calculated using the
      Kaplan-Meier method. The value of each variable as a predictive marker for
      tumoral recurrence was analyzed using Cox regression analysis. Hazard ratios and
      95% confidence intervals were calculated as indicators of relative risk. The
      analysis was applied to the whole cohort and was subsequently repeated in each
      TNM tumoral stage separately. RESULTS: Tumors with p53 protein overexpression
      more frequently recurred and showed lower recurrence-free survival at 5 years.
      However, the association between p53 expression and postoperative outcome was
      statistically significant in stage III tumors only. In this subgroup of patients,
      recurrence-free survival at 60 months was 60% in p53-negative tumors and was 26%
      in p53-positive tumors (p=0.010). In the multivariate analysis, p53 was an
      independent prognostic factor associated with a high risk of recurrence in stage
      III tumors (hazard ratio=2.76; 95% CI, 1.29-5.9; p=0.009). Overexpression of p53
      showed prognostic value as a marker of high risk of recurrence in the form of
      metastases (hazard ratio=2.23; 95% CI, 1.04-4.75), but not as a prognostic marker
      of locoregional recurrence. No relationship was found between the state of p53
      protein and the effect of postoperative adjuvant therapy. CONCLUSION: The p53
      protein does not have the same prognostic value in all tumoral stages. This
      protein is only predictive of high recurrence risk in the subgroup of patients
      with stage III tumors.

PMID- 16420921
TI  - [EUSOMA requirements for breast cancer units in Spain].
AB  - INTRODUCTION: The optimal treatment of breast cancer consists of a
      multidisciplinary approach in specialized units, benefitting patients and leading
      to more rational resource use. Based on these premises, the European Society of
      Mastology (EUSOMA) drew up recommendations designed to provide all European
      countries with high-quality multidisciplinary teams. MATERIAL AND METHOD: We
      present and analyze the results obtained from a survey of breast cancer units in
      241 Spanish hospitals performed by the Breast Diseases Group of the Spanish
      Association of Surgeons. RESULTS: Breast disease was treated in general surgery
      departments in 131 hospitals and Spanish surgeons showed strong interest in
      continuing training (41.2% had a postgraduate degree in mastology).
      Multidisciplinary discussions at weekly intervals took place in 95 hospitals
      (73.6%) hospitals for planning a diagnostic and therapeutic course of action
      specific for each patient. Written protocols for diagnosis and treatment were
      used in 119 departments (90.8%) and quality control measures were applied in 83
      (63.4%). CONCLUSIONS: We stress the need for mandatory requirements in Spain for
      breast cancer units, preferably adapted to the EUSOMA criteria, which are
      accepted by the relevant committee of the European Parliament. Through its Breast
      Diseases Group, the Spanish Association of Surgeons should be involved in
      accreditation standards for breast surgeons and should promote adequate
      specialization programs.

PMID- 16420922
TI  - [Infection rate in clean surgery: follow-up until 30 days after operation].
AB  - INTRODUCTION: Surgical site infections in clean surgery are a significant problem
      and are linked to increasing morbidity and mortality. Consequently, surveillance
      systems should be developed to determine the true value of the infection rate in
      clean surgery and to focus efforts to reduce it. MATERIAL AND METHOD: Five
      hundred twenty-five patients who underwent clean surgery were prospectively
      studied. Demographic characteristics, underlying disease, and data related to
      both surgery and postoperative infection were analyzed. The patients were
      followed-up for 30 days after surgery. RESULTS: Fifty-eight percent of the
      infections were diagnosed after the patient had left hospital. The surgical wound
      infection rate was 2.3%. Patients with one or more risk factors had an infection
      rate of 3.95%. Diabetes mellitus and malignancy were associated with infection
      rates of 9% and 8.2% respectively. CONCLUSION: This type of surveillance, at 30
      days after surgery, provides more accurate data on real infection rates. The most
      important factors associated with infection in this series were diabetes
      mellitus, malignancy and length of surgery.

PMID- 16420923
TI  - [Tracheoesophageal fistula in an intubated patient. Treatment through exclusion
      and esophageal patch].
AB  - Currently, acquired benign tracheoesophageal fistulas are mainly iatrogenic
      lesions produced by prolonged tracheal intubation. Their occurrence in intubated
      patients is infrequent but devastating and their therapeutic resolution is highly
      complex. We present the case of a patient with an extensive tracheoesophageal
      fistula following tracheal intubation that was surgically treated through
      esophageal exclusion (cervical esophagostomy and suture-stapling of the distal
      esophagus) and closure of the tracheal defect using the posterior esophageal
      wall.

PMID- 16420924
TI  - [Solid-pseudopapillary tumor of pancreas].
AB  - Solid-pseudopapillary tumor of pancreas is a very rare neoplasm of low malignant
      potential and unknown origin. It generally occurs in young women and the
      prognosis is usually good after complete surgical removal. Two cases of solid
      pseudopapillary tumor with distinct disease duration are reported.

PMID- 16420925
TI  - [Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm].
AB  - Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by
      Carcangiu when he described its characteristic histology. Clinically and
      morphologically it is considered to be in an intermediate position between well
      differentiated carcinoma of the thyroid (papillary or follicular) and
      undifferentiated or anaplastic carcinoma of the thyroid. However, most authors
      believe it to be an independent entity. The prognosis of this tumor is worse than
      that of classic carcinoma of the thyroid, and most authors advise aggressive
      therapy, which in some cases can achieved prolonged survival. We describe 2
      patients who experienced recurrence after treatment for the primary tumor. The
      recurrences were treated but the clinical courses differed.

PMID- 16420927
TI  - [Sectorization of oncological care. The experience of the United Kingdom].

PMID- 16420926
TI  - [Necrotizing soft tissue infection, with bacteria from the intestines in affected
      tissues].

PMID- 16420928
TI  - [Benign solid liver tumors].
AB  - Benign solid liver tumors are a heterogeneous group of lesions (adenoma, focal
      nodular hyperplasia, hemangioma, etc.) with highly varied epidemiological
      characteristics. Advances in diagnostic methods have improved preoperative
      diagnosis. Magnetic resonance imaging has become the key test, but there is still
      a percentage of cases in which definitive preoperative diagnosis is not feasible.
      The most frequent symptom is abdominal pain, although patients are frequently
      asymptomatic. Surgery is indicated when diagnosis is uncertain or there are
      complications (rupture, hemorrhage, etc.). Because of the risk of malignant
      transformation, adenomas should always be resected. Morbidity and mortality after
      resection of these tumors is very low since excision is limited, performed in
      young people without concomitant disease, and in healthy liver.

PMID- 16420929
TI  - [Pelvic floor disease].
AB  - The pelvic floor is one of the most complex structures of the human body.
      Historically, the approach to pelvic floor disease has been "vertical": the
      anterior compartment was the domain of urologists, the middle compartment was the
      domain of gynecologists with frequent incursions into the female anterior
      compartment, and the posterior compartment was reserved for surgeons. In the last
      few years, a change has occurred in the philosophy underpinning the management of
      these diseases with the development of an integrative "cross sectional" approach
      which affects the physiology, physiopathology, and the definition of these
      diseases as an integrated structure, and which includes urinary and fecal
      incontinence, pelvic organ prolapse, alterations in the perception of urinary
      tract emptying, chronic constipation, sexual dysfunctions, and several chronic
      pain syndromes in the perineal area. We believe that the efforts of the various
      professionals involved in the treatment of these disorders should be pooled and
      that pelvic floor units should be created. These units should be characterized by
      a multidisciplinary approach, since the skills and knowledge necessary for the
      management of these patients requires teams composed of professionals with a
      broad range of competencies.

PMID- 16420930
TI  - [Intraductal papillary mucinous neoplasms of the pancreas].
AB  - INTRODUCTION: Mucin-producing pancreatic tumors account for 1% of all malignant
      tumors of the pancreas. Notable among these are intraductal papillary mucinous
      neoplasms of the pancreas, due to their variable clinical behavior, increased
      frequency, and the controversy surrounding the most suitable treatment and
      diagnostic methods. The aim of this study was to analyze the clinical
      presentation, epidemiological and pathological features, diagnostic methods,
      treatment and survival rates of these tumors. PATIENTS AND METHOD: We performed a
      prospective review of patients with a diagnosis of intraductal papillary mucinous
      neoplasm of the pancreas between 1996 and 2001. Demographic and clinical
      characteristics, diagnostic tests, surgical treatment, tumor characteristics and
      survival rates were studied. RESULTS: There were 8 patients. The mean age was 65
      years. The most common clinical presentation was abdominal pain. The most
      frequent localization was the pancreatic head. The most common diagnostic methods
      used were abdominal computed tomography, endoscopic retrograde pancreatography,
      and serum CA 19.9 levels. Seven patients underwent pancreatic resection and only
      one patient was not surgically treated. The mean follow-up period was 38 months
      with a survival rate of 75% and a recurrence rate of 25%. CONCLUSION: Intraductal
      papillary mucinous neoplasms of the pancreas generally appear in the sixth decade
      of life. The most common presenting symptom is abdominal pain. These neoplasms
      typically occur in the head of the pancreas. The most commonly used diagnostic
      test is computed tomography and the main treatment is early surgical resection.
      The prognosis is good after complete resection, with a 5-year survival rate of 60
      70%.

PMID- 16420931
TI  - [Enteral nutrition with needle catheter jejunostomy in esophageal anastomosis.
      Complications of the technique].
AB  - OBJECTIVE: The aim of this study was to evaluate the presence of complications
      associated with the use of surgical needle catheter jejunostomy and tolerance to
      enteral nutrition. PATIENTS AND METHOD: We performed a retrospective study of 58
      consecutive patients, who underwent esophageal or gastric resection with
      esophageal anastomosis and needle catheter jejunostomy. The variables studied
      were initiation of enteral nutrition, duration of perfusion, complications
      associated with the use of jejunostomy, and tolerance to enteral nutrition.
      RESULTS: Mortality in the series was 1.7%. Infusion of enteral nutrition was
      started at mean of 4.84+/-5.01 days and lasted for a mean of 7.9+/-7.5 days. In
      one patient the jejunostomy could not be used due to catheter obstruction and in
      another 2 patients some resistance to perfusion of nutrition was observed but
      these patients could be fed through the tube. One patient had to undergo
      reintervention due to peritonitis caused by extravasation of the enteral
      nutrition within the peritoneal cavity. Catheter withdrawal was difficult in 2
      patients; of these, 1 patient required investigation of the skin wound under
      local anesthetic. The overall rate of jejunostomy-related complications was
      10.3%. Tolerance of enteral nutrition was acceptable in 41 patients, the infusion
      rate was reduced in 6 patients and infusion was discontinued due to intolerance
      in 10. CONCLUSIONS: Because needle catheter jejunostomy produces low morbidity
      and good tolerance to enteral nutrition, it is a valid alternative in patients
      with esophageal anastomosis.

PMID- 16420932
TI  - [Approach to cytologically-benign recurrent thyroid cysts].
AB  - INTRODUCTION: The aim of this study was to determine the incidence of carcinoma
      in cytologically-benign recurrent thyroid cysts and to evaluate the surgical
      indications in these patients. PATIENTS AND METHOD: We reviewed all patients
      undergoing thyroid surgery between January 1992 and December 2002 for
      cytologically-benign solitary or dominant cystic nodules in multinodular goiter
      that recurred after aspiration. Mixed nodules were excluded. RESULTS: Thirty-four
      patients (29 women and five men) with a mean age of 43 years (18-76) underwent
      surgery. Seventy-five percent were solitary nodules and 25% were dominant nodules
      within a multinodular goiter. The mean number of fine needle aspirations with
      complete drainage was 2.3 (2-3) per patient with hemorrhagic aspirate in 35%.
      Total thyroidectomy was performed in multinodular goiters and lobectomy with
      isthmectomy in solitary nodules. Intraoperative biopsy revealed benign lesions in
      91% and was inconclusive in the remainder; no cases of carcinoma were identified.
      Definitive pathologic findings revealed the nodule to be a papillary carcinoma in
      3 patients (8.8%) and occult papillary carcinoma separate from the cyst in 4
      patients (11.8%). In all these patients intraoperative biopsy showed benign
      disease. The risk of malignancy was higher in cysts larger than 3 cm (23% vs 0%;
      p<0.05). CONCLUSIONS: Given the incidence of carcinoma, surgical resection should
      be considered in recurrent cystic thyroid nodules, especially in those larger
      than 3 cm, regardless cytological study.

PMID- 16420933
TI  - [Contribution of positron emission tomography to the detection and staging of
      breast cancer].
AB  - INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a
      diagnostic imaging tool with multiple applications in oncology. One of the more
      promising applications in breast cancer is noninvasive lymph node staging and
      detection of distant metastases, which may provide useful information about
      prognosis and treatment response. MATERIAL AND METHOD: Published studies on FDG
      PET applications in breast cancer detection and staging were reviewed. We also
      present our own experience in patients referred for preoperative staging of
      breast cancer. RESULTS: FDG-PET is very useful in evaluating dense breasts,
      multicentric disease and breast prostheses. The sensitivity of FDG-PET for nodal
      staging is low, and consequently it cannot replace either sentinel lymph node
      biopsy or histologic examination. However, it is more accurate than another
      noninvasive techniques and is very useful in internal mammary node chain
      evaluation. FDG-PET can improve and maybe replace conventional imaging in
      detecting metastatic disease, especially in high risk patients with
      locoregionally advanced recurrent breast cancer or increased serum tumor markers,
      and helps to characterize unclear findings of anatomic imaging techniques or
      scintigraphy. CONCLUSIONS: FDG-PET is useful in breast cancer staging. It
      complements and even improves information from other diagnostic techniques and
      changes therapeutic management in a high proportion of patients.

PMID- 16420934
TI  - [Risk factors for acute abdominal wall dehiscence after laparotomy in adults].
AB  - INTRODUCTION: Total evisceration consists of protrusion of the abdominal viscera
      due to dehiscence of all the planes of the abdominal wall after laparotomy. The
      greater the number of risk factors, the greater the probability of evisceration.
      PATIENTS AND METHOD: We performed a retrospective study of patients with
      evisceration treated in the previous 9 years. RESULTS: Among 12,622 patients who
      underwent laparotomy, 57 eviscerations were detected (45 men, 12 women; mean age
      70 years). The diagnosis was peritonitis in 26 patients and intestinal occlusion
      in 19. Emergency surgery was performed in 48 patients. Reintervention was
      performed in 12 patients. Postoperative complications were found in all patients,
      especially wound infection and paralytic ileus. The main clinical finding was
      staining of the dressing. Laboratory investigations revealed leukocytosis,
      hypoproteinemia, and anemia. Surgical repair consisted of simple closure and/or
      retention sutures; mesh was associated in 6 patients. Subsequent morbidity was
      77%. Twenty-six patients required admission to the intensive care unit. The mean
      length of hospital stay was 28.5 days. The were 41 recoveries (72%) and 16 deaths
      (28%). Review of 18 parameters involved in evisceration showed that 80% (45
      patients) presented 9 or more risk factors. CONCLUSIONS: Evisceration is a
      serious occurrence that produces high morbidity and mortality. The most frequent
      risk factors in our series were age greater than 65 years, hemodynamic
      instability, increased intra-abdominal pressure, emergency surgery, infection of
      the wound or abdominal wall, hypoproteinemia and anemia. Because these risk
      factors can be predicted, when several are grouped together, reinforcement should
      be used when closing the abdominal wall.

PMID- 16420935
TI  - [Surgical treatment of primary hyperparathyroidism in pregnancy].
AB  - Primary hyperparathyroidism during pregnancy is a pathological entity with an
      unknown incidence that presents certain physiological, therapeutic and prognostic
      characteristics leading to greater difficulty in diagnosis and a high risk of
      complications. We present the case of a 16-week pregnant woman who presented with
      asymptomatic hypercalcemia secondary to a solitary parathyroid adenoma. Since
      conservative measures produced no improvement, surgery was performed in the
      second trimester of pregnancy, with satisfactory pre- and postnatal results.
      Surgery in the second trimester constitutes a safe alternative to conservative
      treatment.

PMID- 16420936
TI  - [Giant solitary fibrous tumor of the pleura].
AB  - Primitive neoplasms of the pleura are uncommon. Solitary fibrous tumor of the
      pleura (SFTP) is a benign variety of primitive pleural tumor, which is usually
      asymptomatic and discovered as an incidental finding. However, these tumors can
      sometimes become locally aggressive and can even be life-threatening. The
      treatment of choice is surgical resection. We report a case of SFTP in a 78-year
      old woman with no relevant history, who presented with marked respiratory
      insufficiency and who required extended posterolateral thoracotomy to achieve
      complete resection of an SFTP weighing 2 kg.

PMID- 16420938
TI  - [Arterial branch originating in the abdominal aorta].

PMID- 16420937
TI  - [Giant retroperitoneal liposarcoma].
AB  - Liposarcoma is a malignancy of fat cells and is the most frequent soft tissue
      sarcoma localized in the retroperitoneum. It can reach substantial proportions.
      It is a slow-growing tumor, and the most frequent symptom is nonspecific
      abdominal pain and diffuse abdominal enlargement. Treatment is radical surgery
      and complete resection is essential for local control of the disease. We present
      a case of giant right retroperitoneal liposarcoma, which was well-encapsulated
      and could be completely excised. The patient is currently in follow up and at 2
      years is disease-free.

PMID- 16420939
TI  - [Many published survival analyses may be intrinsically flawed. The cases of
      transplantation and cancer].

PMID- 16420940
TI  - [Video-assisted surgery in the treatment of pneumothorax].

PMID- 16420942
TI  - [Massive liver metastases from colorectal cancer].

PMID- 16420943
TI  - [Abdominal abscess drainage. Advantages of fibrinolytic agents].
AB  - Image-guided percutaneous abscess drainage has become the standard method of
      treatment for most abdominal abscesses. In many cases, it should be considered
      the treatment of choice, but there are certain circumstances that require
      specific approaches and methods. Typical abscesses within solid parenchymal
      organs or those in the peritoneal spaces can be reliably detected by imaging
      techniques and efficiently drained. Abscesses that are multiple or long and
      circuitous require careful placement of one or more catheters. Management of the
      drainage catheters includes irrigation with saline solution to prevent
      obstruction. Despite the use of saline irrigations and large caliber catheters,
      catheter drainage sometimes fails and conventional surgery is required. In
      selected cases, fibrinolytic agents have been proved to be effective in
      shortening drainage times and length of hospital stay. The use of fibrinolytic
      agents in the drainage of some anatomical sites, such as the spleen and pancreas,
      is controversial and the technique should be meticulously selected. Successful
      treatment is most likely when an interdisciplinary approach is used. The present
      article reviews the state of the art of the use of fibrinolytic agents to improve
      percutaneous abdominal abscess drainage.

PMID- 16420944
TI  - [Informed consent in the surgical patient. Reflections on the basic law of
      patient autonomy].
AB  - Informed consent is the final step in informing the surgical patient. The basic
      law of patient autonomy specifies the conditions in which patient authorization
      should be given with the aim of guaranteeing that a free decision is made.
      However, surgeons are sometimes faced with clinical situations in which it is
      difficult to obtain informed consent, whether because the patient is unable to
      provide consent or because of the need to intervene in a life-threatening
      situation, or because the informed consent document must specify the risks and
      consequences of the intervention. The present article aims to analyze what
      happens when the patient is unable to provide consent ("consent by
      representation") and the characteristics of the informed consent document
      according to the stipulations of the basic law of patient autonomy.

PMID- 16420945
TI  - [Treatment of thoracic esophageal perforations].
AB  - OBJECTIVE: To evaluate the results of the treatment of patients with thoracic
      esophageal perforation in order to determine the most appropriate management of
      this entity. PATIENTS AND METHOD: We performed a retrospective study of 21
      patients (mean age 59 years; 24-82) who presented with thoracic esophageal
      perforation to our hospital between 1991 and 2004. RESULTS: In 13 patients (62%)
      treatment was performed within 24 hours. In the remaining 8 patients the mean
      delay was 7.2 (2-12) days. In 4 patients (26%) the perforation was confined to
      the mediastinum and conservative treatment was provided. Of these patients, 1
      developed empyema and underwent esophageal resection. Extramediastinal
      involvement was confirmed in 17 patients (73%) and was treated by a variety of
      surgical procedures: esophagectomy (n=2), drainage alone (n=2), primary closure
      (n=2) and reinforced primary repair (n=11). Two patients with simple closure and
      1 with reinforced primary closure developed leakage of the suture line resulting
      in death. The 3 patients who underwent esophagectomy survived. In patients with
      perforation confined to the mediastinum mortality was 0%, whereas in those with
      extramediastinal involvement mortality was 23%. CONCLUSIONS: Thoracic esophageal
      perforation leads to high mortality rates and requires early diagnosis and
      immediate treatment. Conservative management is appropriate in only a few
      selected patients. When surgical treatment is indicated, we advocate reinforced
      primary repair regardless of the interval between injury and operation, except
      when the esophagus is in such poor condition that esophagectomy is the only
      option.

PMID- 16420947
TI  - [Prognostic value of invasive growth pattern in sporadic colorectal cancer].
AB  - INTRODUCTION: Invasive growth pattern refers to the type of growth of the tumoral
      margins, whether infiltrating or noninfiltrating. The aim of the present study
      was to evaluate the invasive growth pattern (infiltrating/noninfiltrating) in
      colorectal cancer as a prognostic factor related to tumoral recurrence and
      survival. PATIENTS AND METHOD: We studied 105 patients with colorectal cancer who
      underwent radical surgery in the General Surgery Department of the Hospital
      Universitario Medico-Quirurgico of Jaen between 1991 and 1997. The mean length of
      follow-up was 54 months. Regarding invasive growth pattern, 2 types of growth
      have been described: infiltrating and noninfiltrating. RESULTS: Tumoral invasion
      was infiltrating in 65 patients (62%). Tumoral recurrence: in 14 patients (13.3%)
      distant metastases were diagnosed. In the univariate analysis, infiltrative
      pattern was a statistically significant risk factor for distant metastases;
      however, this factor did not retain statistical significance in the multivariate
      analysis. Survival: 30 patients (28.5%) died from causes directly related to the
      neoplastic disease. The mean survival was 55 months. Infiltrating growth pattern
      was a statistically significant independent risk factor for death (HR = 2.50; 95%
      CI = 1.05-5.88). CONCLUSIONS: Infiltrating growth pattern was significantly
      related with the disease-free interval before metastases. Infiltrating growth was
      an independent prognostic factor of survival in colorectal cancer.

PMID- 16420946
TI  - [Laparoscopic versus mini-laparotomy cholecystectomy].
AB  - OBJECTIVES: To describe differences in operating time, pain scores, analgesic
      consumption, complications, length of hospital stay, and quality of life in
      laparoscopic cholecystectomy (LC) vs mini-laparotomy cholecystectomy (MLC).
      PATIENTS AND METHOD: Between 1991 and July 1999, we performed a study of 1041
      patients with gallstones who underwent LC (group A, n = 421 patients) or MLC
      (group B, n = 620 patients). Age, sex, ASA score, pain scores (visual analog
      scale), analgesic and antiemetic consumption, operating time, complications and
      length of hospital stay were recorded. Nottingham Health Profile questionnaires
      were completed by a subgroup of 200 patients, and respiratory response was
      evaluated using a Fokuda spirometer before surgery and at 24 and 48 hours after
      surgery. Patient satisfaction and quality of life were evaluated. The results
      were interpreted using the SPSS program and descriptive statistics were performed
      with p = 0.05. RESULTS: The mean age was 48.9 +/- 14.2 years; 80.5% of the
      patients were women; 87.88% of the patients were ASA I. Elective surgery was
      performed in 89.78%. The mean operating time was 94 +/- 45 minutes in LC and was
      108 +/- 48 minutes in MLC (p < 0.001). LC was associated with lower postoperative
      pain (0 = 68.88%), lower analgesic-antiemetic requirements (0 = 9.03%) and
      shorter length of hospital stay. Complications were significantly more frequent
      in group B (p = 0.05); two patients in group B died within 30 days of surgery
      (0.32%). CONCLUSIONS: LC appears to be associated with lower pain scores and
      analgesic-antiemetic requirements and shorter recovery times than MLC. The
      results in terms of quality of life in LC were excellent.

PMID- 16420948
TI  - [Clinical pathway for the treatment of primary spontaneous pneumothorax in a
      general surgery department].
AB  - INTRODUCTION: Primary spontaneous pneumothorax (PSP) is a common entity.
      Treatment varies widely across different health systems and even among doctors in
      the same department. In our general surgery department 30 to 40 patients with PSP
      are treated each year and there is significant variability in care delivery. This
      prompted the development of a clinical pathway (CP) based on analysis of the
      process, a search for studies with the greatest scientific evidence and
      professional consensus. The aim of this study was to present the results after 1
      year's evaluation of the CP. PATIENTS AND METHOD: A series of 34 patients treated
      in the year prior to the design of the pathway was analyzed to identify weak
      points and areas for improvement. To address these weak points the CP included
      associated protocols and principal documents. Thirty-one patients included in the
      CP were treated over 1 year and the results were compared with those of the pre
      pathway series. RESULTS: The mean length of stay in the pre-pathway patients was
      7.3 days compared with 5.0 days in the pathway patients. The number of
      radiographs also fell from 4.3 to 3.2. The rate of complications and re
      admissions was similar in both groups. The mean cost per process decreased from
      1863 Euro to 1168 Euro. CONCLUSION: The CP for pneumothorax reduced both
      variability in professional care patterns and hospital costs, justifying the work
      involved in its development and implementation.

PMID- 16420949
TI  - [Composite prostheses for the repair of abdominal wall defects: comparative study
      of physical and/or chemical barriers].
AB  - INTRODUCTION: Composite biomaterials designed for the repair of abdominal wall
      defects are usually composed of a reticular component and a second component, or
      barrier, which is laminar (absorbable or non-reabsorbable) and which is placed in
      contact with the visceral peritoneum. This study was designed to evaluate how the
      composition of this second component affects the biological behavior of the
      biomaterial and the formation of adhesions. MATERIAL AND METHODS: Defects (7 x 5
      cm) comprising all the tissue planes except the skin were created in the anterior
      abdominal wall of white, New Zealand rabbits. In group A (n = 12) the defects
      were then repaired with composite prostheses with a non-reabsorbable physical
      barrier, polypropylene + ePTFE (PL + ePTFE) and PL + polyurethane (PL + PU). In
      group B (n = 12) the defects were repaired with a reabsorbable chemical barrier,
      polyester + a polyethyleneglycol/glycerol film (PO + gl) and PL + hyaluronate (PL
      + hy). Fourteen days after surgery, the animals were sacrificed and specimens
      were taken for light and scanning electron microscopy and immunohistochemical
      labeling for macrophages (RAM-11). Adhesions forming at the prostheses/visceral
      peritoneum interface were quantified. RESULTS: All the materials showed optimal
      tissue infiltration and mesothelialization. Adhesion formation was similar in
      prostheses with a physical barrier (PL + ePTFE, 0.49 +/- 0.14%; PL-PU, 0.29 +/-
      0.2%). In contrast, those with a chemical barrier showed a significant difference
      in adhesion formation (PO + gl, 0.55 +/- 0.06%; PL + hy, 18.55 +/- 4.96%; p <
      0.05). CONCLUSIONS: Physical barriers seem to induce similar adhesions, while
      adhesions formed to prostheses with chemical barriers can vary considerably,
      possibly depending on the chemical composition of the barrier.

PMID- 16420950
TI  - [Jejunal diverticulitis. A rare cause of acute abdomen].
AB  - Non-Meckelian jejunoileal diverticula are more frequently diagnosed in men aged
      more than 50 years old. They are a rare cause of acute abdomen. They are usually
      asymptomatic and are estimated to cause complications in 10-20% of cases. We
      present the recently diagnosed case of an 82-year-old man admitted to our
      hospital.

PMID- 16420951
TI  - [Pancreaticopleural fistula: diagnostic tests and treatment].
AB  - Pancreaticopleural fistula is an uncommon clinical entity that appears in
      patients with a history of chronic pancreatitis. Apropos of the case of a 40-year
      old man in our hospital, we reviewed the literature and found 40 publications
      with little more than 100 patients. All of these publications highlight the
      atypical presentation with dyspnea as the first symptom and stress that diagnosis
      is based on magnetic resonance pancreatography. Endoscopic retrograde
      cholangiopancreatography is used in confusing cases and in planning the optimal
      surgical approach. Initial treatment should consist of conservative medical
      therapy, including total parenteral nutrition and somatostatin or its analogues.
      If the fistula persists or recurs, various options are available such as surgery,
      placement of a transpapillary pancreatic stent or nasopancreatic tube. The
      overall mortality rate from pancreaticopleural fistula is approximately 5%.

PMID- 16420953
TI  - [Image of the month].

PMID- 16420952
TI  - [Intra-abdominal desmoid tumor].
AB  - Aggressive fibromatosis (desmoid tumor) are rare connective tissue tumors that
      occur sporadically or in association with familial adenomatous polyposis. The
      etiology is unknown and clinical findings depend on growth into neighboring
      structures. Biopsy is required to establish the diagnosis. The treatment of
      choice is surgery. We report a case with unusual localization in this form of
      presentation. The patient remains asymptomatic 15 months after surgery.

PMID- 16420955
TI  - Dissociation of bipolar hemiarthroplasty of the hip after dislocation. A report
      of five different cases and review of literature.
AB  - Little information is available about the rare but serious disadvantage of
      dissociation of modular components during dislocation or after close reduction in
      the bipolar hemiarthroplasty of the hip. In most cases, simple dislocation after
      primary bipolar hemiarthroplasty can safely be reduced by close methods.
      Dissociation leads almost always to reoperation and possible revision of the
      prosthesis. To avoid this complication, strict adherence to the surgical
      technique during the initial procedure and extra precaution during close
      reduction are recommended, in order to provide enhanced security over component
      disassembly. In the five cases presented in this study, dissociation is reported
      at different circumstances, along with the different methods of treatment
      required in each patient.

PMID- 16420954
TI  - Are there differences in clinical and laboratory parameters between children and
      adults with American visceral leishmaniasis?
AB  - A prospective study on 23 patients with American visceral leishmaniasis (VL),
      comparing clinical and laboratory parameters of 14 children (mean age of 3.85+/
      3.39 years) to nine adults (27.4+/-10.90 years) was performed in Sao Luis,
      Maranhao, Brazil, between August 2000 and July 2002. Data were collected at
      entrance (day 0), end of treatment, as well as 120 and 210 days after treatment
      using a protocol chart containing patient identification, clinical and laboratory
      data. N-Methylglucamine antimonate administered at the dose of 20mg/Sb5+/kg/day
      for 20-30 days was successfully used in all patients. Patients were followed for
      1 year after treatment, and no relapses were observed. A prolonged duration of
      the disease, lymphadenopathy and bleeding predominated in adult patients, while
      hepatomegaly and skin-mucosal pallor were more frequent in children. Disease was
      longer and more severe in adults than in children. Although both groups exhibited
      a trend toward normalization of hematological and biochemical parameters, more
      children returned sooner to normal values than adults. Difference in clinical or
      laboratory parameters between children and adults did not indicate the need for
      different clinical or therapeutic approaches.

PMID- 16420956
TI  - Covert colour processing in colour agnosia.
AB  - Patients with colour agnosia can perceive colours and are able to match coloured
      patches on hue, but are unable to identify or categorise colours. It is a rare
      condition and there is as yet no agreement on the clinical definition or a
      generally accepted explanation. In line with observations from object agnosia and
      prosopagnosia, we hypothesised that (some of) these patients might still be able
      to process colour information at an implicit level. In this study, we
      investigated this possibility of implicit access to colour semantics and colour
      names in a man (MAH) who suffers from developmental colour agnosia. We designed
      two experimental computer tasks: an associative colour priming task with a
      lexical decision response and a reversed Stroop task. The results of these
      experiments suggest that there is indeed automatic processing of colour, although
      MAH was unable to explicitly use colour information.

PMID- 16420957
TI  - Age decreased steady-state concentrations of genistein in plasma, liver, and
      skeletal muscle in Sprague-Dawley rats.
AB  - Soy isoflavones are associated with low incidence of cardiovascular diseases
      (CVD) and hormone-dependent cancers, but no solid information is available on the
      relative deposition of isoflavones in the body as a function of age. One-year-old
      (adult) male Sprague-Dawley rats were fed control diet or one of three high
      genistein isoflavone (HGI) diets at a dose of 62, 154, or 308 genistein mg/kg
      (ppm) diet for 5 weeks; 2-year-old (old) were fed a dose of 154 or 308 ppm.
      Steady-state genistein concentrations in plasma, liver, and gastrocnemius muscle
      of the adult rats after 12 h fast revealed a linear dose-dependent manner (P < or
      = 0.0001). However, there was no such relationship in the old rats. Nevertheless,
      old rats fed the 308 ppm genistein diet had significantly lower steady-state
      genistein concentrations in plasma and liver than the adult rats did (P < or =
      0.05); but similar genistein concentration in muscle. The results of this study
      indicate that steady-state genistein concentrations in tissues of adult rats
      after 12 h fast exhibited a dose-dependent fashion and were diminished in
      specific tissues by age.

PMID- 16420958
TI  - Development, freezability and amino acid consumption of bovine embryos cultured
      in synthetic oviductal fluid (SOF) medium containing amino acids at oviductal or
      uterine-fluid concentrations.
AB  - In this study, we examined the development, freezability and amino acid
      consumption of in vitro produced bovine embryos cultured in a chemically defined
      medium (SOF+polyvinyl alcohol), supplemented with 24 amino acids at
      concentrations measured in bovine oviductal or uterine fluid. Amino acids at
      concentrations in oviductal fluid tested by Elhanssan (EOAA) significantly
      improved development to the hatched blastocyst stage, compared to Sigma amino
      acid solutions BME and MEM (SAA). Amino acids at concentrations in uterine fluid
      tested by Li (LUAA) were not compared to SAA, and development in LUAA was not
      significantly different from development in EOAA. Amino acids at concentrations
      in uterine fluid tested by Elhanssan (EUAA) significantly reduced cleavage rate
      and blocked further embryo development. When the IVF embryos were cultured in
      EOAA for 48, 72, 96, or 120 h and then transferred to LUAA, blastocyst and
      hatched blastocyst rates were not significantly affected. The freezability of
      blastocysts cultured in EOAA for the first 72 h and then moved to LUAA was
      improved compared to that in SAA. During the 1-8-cell stages, embryos secreted
      all 23 amino acids (total, 6,368 pmol/embryo). During the 8-cell to morula
      stages, embryos continued to secrete 21 amino acids (total, 2,495 pmol/embryo),
      meanwhile embryos began to absorb Arg (70 pmol/embryo) and Gln (18 pmol/embryo).
      After the morula stage, embryos began to absorb 15 amino acids including Glu,
      Gly, Arg, and Gln (total, 2,742 pmol/embryo) and secreted eight amino acids
      (total, 1,616 pmol/embryo). Embryos absorbed only Arg (183 pmol/embryo) and
      secreted the other 22 amino acids (total, 3,697 pmol/embryo) when the culture
      medium was not changed during the entire culture period (zygote to blastocyst).

PMID- 16420959
TI  - A field investigation of intra-cervical insemination with reduced sperm numbers
      in gilts.
AB  - A novel insemination catheter with a smaller polyurethane tip for deeper
      insertion into the cervix of gilts was compared with the conventional catheter.
      The novel catheter could be inserted 31.4 mm deeper than the conventional
      catheter into the gilt cervix, but the difference diminished with parity until
      the sixth parity when there was no difference in penetration depth between the
      catheters. In Experiment 1, cyclic gilts were inseminated upon display of oestrus
      (back pressure test) in the presence of a boar (0 h) and 24 h later. The control
      group (n = 300) were inseminated with 2 x 10(9) total spermatozoa and the
      treatment group (n = 300) with 1 x 10(9) total spermatozoa per inseminate, in
      both cases utilising the novel insemination catheter. No significant differences
      were observed for farrowing rate and litter size, the values of which were those
      expected for natural mating. In Experiment 2, 66 cyclic gilts were subjected to
      the same heat detection and service regime as for Experiment 1 but were served
      with <1 x 10(9) total sperm cells per inseminate using the new device. Conception
      rates and embryo counts were recorded. Conception rate declined with <500 x 10(6)
      spermatozoa, and number of embryos (a reflection of potential litter size) was
      significantly reduced. Use of the new catheter for gilts with 1 x 10(9) total
      sperm cells per inseminate will achieve commercially acceptable fertility and
      fecundity levels, and offer substantial commercial benefits with more rapid
      genetic gains.

PMID- 16420960
TI  - The effect of dietary supplementation with blueberry, alpha-tocopherol or
      astaxanthin on oxidative stability of Arctic char (Salvelinus alpinus) semen.
AB  - The objective was to determine the oxidative stability of Arctic char (Salvelinus
      alpinus) semen following dietary supplementation with lowbush blueberry
      (Vaccinium angustifolium) product, alpha-tocopherol, alpha-tocopherol+blueberry
      product, or alpha-tocopherol+astaxanthin. Sperm lipid peroxidation was initiated
      by challenging with ferrous sulphate/ascorbic acid (Fe(++)/Asc) at level of
      0.04/0.2 mmol/L. Addition of blueberry, alpha-tocopherol, or both to char diets
      inhibited semen lipid peroxidation by: (a) decreasing the rate of sperm lipid
      peroxidation, an effect which was more pronounced with alpha-tocopherol
      treatments; and (b) increasing the antioxidant potential of seminal plasma, based
      on the lipid peroxidation process of sperm and an in vitro chicken brain tissue
      model. Dietary supplementation with astaxanthin and alpha-tocopherol had the same
      effect as the supplementation with alpha-tocopherol alone on inhibiting the lipid
      peroxidation process of sperm and chicken brain. Catalase-like activity increased
      significantly in sperm of fish fed alpha-tocopherol, blueberry, or both. There
      was a negative correlation (r= -0.397, P < 0.05) between catalase-like activity
      in sperm cells and the rate of sperm lipid peroxidation. Seminal plasma alpha
      tocopherol levels increased significantly in fish supplemented with alpha
      tocopherol alone or in combination with blueberry or astaxanthin. There were
      negative correlations between seminal plasma alpha-tocopherol levels and lipid
      peroxidation rates of sperm cells (r= -0.625, P < 0.01) and brain tissue (r= 
      0.606, P < 0.01). In conclusion, dietary supplementation of blueberry product or
      alpha-tocopherol inhibited lipid peroxidation in Arctic char semen. Further
      experiments are needed to test the effect of dietary blueberry and antioxidants
      on Arctic char semen quality during liquid and cryopreserved storage.

PMID- 16420961
TI  - Purification of MINUS: A negative regulator of microtubule nucleation in a
      variety of organisms.
AB  - Microtubules (MT) are important for cell behavior and maintenance, yet the
      factors regulating MT assembly in vivo remain obscure. In a biochemical search,
      we have isolated a small (4.7 kDa) acidic, phosphorylated polypeptide, which we
      named MINUS (microtubule nucleation suppressor) for its activity to inhibit MT
      nucleation [P. Fanara, B. Oback, K. Ashman, A. Podtelejnikov, R. Brandt, EMBO J.
      18 (1999) 565]. Here, the purification strategy was optimized and the polypeptide
      purified to homogeneity from bovine brain, Drosophila, Caenorhabditis elegans and
      yeast. Amino acid analysis showed similar composition of MINUS from different
      species. In particular, MINUS was rich in glycine, threonine, isoleucine, leucine
      and acidic amino acids. Inductively coupled plasma mass spectrometry revealed a
      large peak for phosphorus confirming its identity as a phosphopeptide. For
      further purification, MINUS was separated as a single peak on reverse phase-HPLC
      (RP-HPLC). Preliminary sequence analysis suggested MINUS to be N-terminally
      blocked. However, conventional enzymatic digestions did not reveal differences in
      the peak profile compared to undigested MINUS. Hence, partial acid hydrolysis and
      proteinase K digestion was performed followed by RP-HPLC. The proteinase K
      digested peaks were subjected to Edman degradation (first peak, ser-pro-ser/gly
      ser; second peak, tyr/arg-leu), mass spectrometry (no result) and MALDI analysis
      (no result). Collectively, the data suggest that MINUS belongs to a new class of
      MT assembly regulators. Sequence information and antibody development will be
      useful to examine its biological role in a definitive manner.

PMID- 16420962
TI  - No evidence for an association of ocular adnexal lymphoma with Chlamydia psittaci
      in a cohort of patients from the Netherlands.
AB  - Extra-nodal marginal zone B cell lymphomas (MZBCLs) of the mucosa-associated
      lymphoid tissues (MALT) arise at sites of chronic antigenic stimulation due to
      organ-specific autoimmunity or infections, like Helicobacter pylori-associated
      chronic gastritis and Borrelia burgdorferi dermatitis. Recently, conflicting data
      have been published regarding a possible association between Chlamydia psittaci
      and ocular adnexal MZBCL. In the present study, we analyzed a cohort of ocular
      adnexal MZBLs from the Netherlands for the presence of C. psittaci DNA. We found
      no evidence for the presence of C. psittaci DNA in any of the tumor samples
      studied. Our data do not support a role for C. psittaci in the pathogenesis of
      ocular adnexal lymphomas in patients from the Netherlands.

PMID- 16420963
TI  - The posterior attic: An observational study of aboriginal Australians with
      chronic otitis media (COM) and a theory relating to the low incidence of
      cholesteatomatous otitis media versus the high rate of mucosal otitis media.
AB  - OBJECTIVE: The incidence of COM without cholesteatoma in Australian aboriginals
      is quoted as being between 25 and 47%. The incidence of cholesteatomatous OM is
      very low in comparison (between 1 and 3%). A comprehensive literature search
      found no studies offering an explanation for the large discrepancy between these
      two types of OM. We offer a theory to account for the disproportionate rates of
      the two types of OM together with an observational study on aboriginals with COM
      to substantiate our argument. METHOD/RESULTS: The crux of our hypothesis centres
      on the anatomy of the posterior attic. We found that in a study of 40 aboriginal
      patients undergoing tympanoplasty with audiometric evidence of an intact
      ossicular chain that, after posterior tympanomeatal flap elevation, no part of
      the incudostapedial assembly was visible in 95% of cases denoting its location
      behind the posterior attic wall. CONCLUSION: We hypothesise that in aboriginal
      ears the resulting 'crowding' of the posterior attic by the incudostapedial
      assembly results in narrowing of the epitympanic space which compromises
      atticoantral drainage, thus leading to mucosal COM, however supporting the
      posterior-superior segment of the tympanic membrane, impeding the formation of a
      retraction pocket, and cholesteatoma formation migrating into the mastoid antrum.

PMID- 16420964
TI  - Nitric oxide synthases are associated with bronchial dysplasia.
AB  - Recent studies suggest that reactive oxygen (ROS) and nitrogen species (RNS) are
      highly associated with the pathogenesis of cigarette smoke related lung diseases
      but their role in the malignant conversion of bronchial epithelium is unclear.
      The immunohistochemical expression of inducible, endothelial and neuronal nitric
      oxide synthases (iNOS, eNOS and nNOS) and nitrotyrosine as a biomarker of
      oxidative/nitrosative stress was evaluated in 79 cases including 13 non-smokers,
      20 smokers without chronic obstructive pulmonary disease (COPD), 22 with COPD and
      24 with metaplasia-dysplasia-sequence of the bronchial epithelium. Normal lung of
      non-smokers was mainly negative for nitrotyrosine, while it was higher in the
      alveolar macrophages of cigarette smokers and COPD than in non-smokers (p=0.025,
      p<0.001), and in the alveolar epithelium of smokers and COPD than in non-smokers
      (p=0.049). There were no major differences in the nitrotyrosine immunoreactivity
      between the metaplastic/dysplastic lesions and bronchial epithelium of cigarette
      smokers. Inducible NOS and nNOS were mainly non-detectable or weak in the normal
      looking bronchial epithelium of smokers and COPD, whereas metaplasia and
      dysplasia showed positivity for iNOS (22/24) and nNOS (14/24) in the majority of
      cases. Strong immunoreactivity for iNOS and nNOS was also found more often in
      dysplastic than metaplastic (p=0.011 and p=0.049, respectively) specimens. Thus,
      smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS
      immunoreactivity in the metaplasia-dysplasia-lesions suggests a divergent role of
      NOSs in lung carcinogenesis.

PMID- 16420965
TI  - Flow cytometry-based method to analyze the change in Tau phosphorylation in a
      hGSK-3beta and hTau over-expressing EcR-293 cell line.
AB  - Neurofibrillary tangles are composed of insoluble aggregates of microtubule
      associated protein Tau. In the pathology of Alzheimer's disease (AD),
      accumulation of hyperphosphorylated Tau results in formation of paired helical
      filaments. One of the main candidate to hyperphosphorylate Tau in AD is glycogen
      synthase kinase 3beta (GSK-3beta). Here we introduce a non-neuronal cell line,
      stably co-expressing human Tau and GSK-3beta proteins, where the effect of
      potential kinase inhibitors on Tau phosphorylation can be monitored. The aim of
      our study was to establish a new flow-cytometry-based method to quantitatively
      analyze the changing of Tau phosphorylation, which is a suitable alternative to
      the well-accepted but non-quantitative Western blot technique. Our results
      demonstrate that the flow cytometry-based method is a convenient tool to analyze
      the effect of GSK-3beta inhibitors on Tau phosphorylation. This new approach
      provides appropriate throughput for screening purposes in preclinical research
      for characterization of GSK-3beta inhibitors, as potential drug candidate to cure
      Alzheimer's disease.

PMID- 16420966
TI  - 17 beta-Estradiol may affect vulnerability of striatum in a 3-nitropropionic acid
      induced experimental model of Huntington's disease in ovariectomized rats.
AB  - The aim of present study was to clarify the role of female sex hormones in the
      development and course of neurodegenerative disease in an experimental model of
      Huntington's disease induced by 3-nitropropionic acid (NPA) (30 mg/kg
      intraperitoneally (i.p.)/day for 4 days) in ovariectomized rat. Gonadectomy
      prompted oxidative stress and cell death evaluated by the detection of caspase-3,
      whereas 3-nitropropionic acid enhanced the oxidative stress induced by
      ovariectomy and it triggered cell damage characterized by increases of LDH
      levels. These changes were prevented by administration of 17 beta-estradiol. Our
      findings suggested that: (i) ovariectomy induced oxidative stress and apoptosis
      in the brain; (ii) 3-nitropropionic acid exacerbated oxidative stress induced by
      ovariectomy and shifting cell to cell death; and (iii) 17 beta-estradiol
      administration decreased oxidative stress and cell death induced by ovariectomy
      and 3-nitropropionic acid. These results revealed that sex ovarian hormones play
      a important role in onset and development of neurodegenerative diseases, as well
      as neuroprotective effects of 17 beta-estradiol against the changes induced
      ovariectomy and ovariectomy plus 3-nitropropionic acid.

PMID- 16420967
TI  - Improved efficacy of DNA vaccination against breast cancer by boosting with the
      repeat beta-hCG C-terminal peptide carried by mycobacterial heat-shock protein
      HSP65.
AB  - Studies have demonstrated that active-specific immunotherapy has potential for
      controlling mammary tumor progression. Human chorionic gonadotropin (hCG) is
      expressed and extremely sensitive, easily detectable and highly correlated with
      breast cancer. We developed a gene vaccine using a plasmid vector to deliver the
      six copies of 10-amino acid residues of beta-hCG 109-118 and beta hCG C-terminal
      37-amino acid (CTP37). BALB/c female mice were immunized with a combination of
      pCR-HBc-X6-betahCGCTP37 DNA vaccine and HSP-X6-betahCGCTP37 protein vaccine. pCR
      HBc-X6-betahCGCTP37 DNA vaccine were injected intramuscularly three times, on
      days -46,-25 and -11 and HSP-X6-betahCGCTP37 protein were applied two times, 21
      and 14 days before tumor cell challenge. We assessed a combined DNA and protein
      vaccine for its effect of against murine EMT6 mammary tumor cells. In this study,
      animals vaccinated DNA vaccination boosting with the repeat beta-hCG C-terminal
      peptide carried by mycobacterial heat-shock protein HSP65 induced higher avidity
      antibodies and effectively inhibited the growth of tumor, compared with treatment
      using DNA alone or BCG priming HSP-X6-betahCGCTP37 protein boosting. The data
      presented demonstrate that improve immunogenicity of DNA vaccination by boosting
      with the repeat beta-hCG C-terminal peptide carried by mycobacterial heat-shock
      protein HSP65, which should prove useful in the development of new DNA vaccine
      against growth factors for cancer immunotherapy.

PMID- 16420968
TI  - Half-day urotherapy improves voiding parameters in children with dysfunctional
      emptying.
AB  - OBJECTIVES: Children with voiding dysfunction benefit from intensive bladder
      emptying re-education; however, hospitalization for such training is not always
      financially viable or realistic. The aim of this study was to evaluate whether
      half-day voiding re-education in pairs improved immediate and mid-term voiding
      parameters. METHODS: 48 children (mean age, 8.9 years; 54% male) identified in
      the urotherapy clinic as having either (1) abnormal uroflow curves, (2) a
      postvoid residual urine (PVRU)>10% of voided volume, or (3) proven dysfunctional
      voiding, were recruited and age- and gender-matched. Training over a half day
      included postural instruction, abdominal wall muscle pattern recognition, pelvic
      floor muscle relaxation training, and supervised voiding. Data from the initial
      clinic visit was compared to that after training, and at 1 and 3 mo follow-up.
      Families completed a questionnaire after the session. RESULTS: Urine flow curves
      were abnormal in 76.2% of initial clinic visit voids, 14% of patients after the
      half-day training session, and 11.7% of children at the 3-mo follow-up. Initial
      emptying efficiency (voided volume as a percentage of total bladder volume for
      that void) and mean PVR significantly improved following half-day training with
      gains maintained at both follow-up visits. CONCLUSION: Training children in pairs
      over a half day resulted in significantly improved bladder emptying that was
      sustained at the 3-mo follow-up.

PMID- 16420969
TI  - Depressed contractile responses to neurokinin A in idiopathic but not neurogenic
      overactive human detrusor muscle.
AB  - OBJECTIVE: The role of tachykinins such as neurokinin A in regulating bladder
      function is unclear, but NK2 receptors seem to mediate contraction in the human
      bladder and it has been suggested that these peptides may have a role in the
      pathophysiology of bladder dysfunction. The present study investigates neurokinin
      receptor-mediated contractility of detrusor muscle in the idiopathic overactive
      and neurogenic overactive bladder and investigates the neurokinin receptor
      subtypes involved. METHODS: Human bladder was obtained from patients undergoing
      cystectomy (normal) or clam cystoplasty (idiopathic overactive) and from patients
      with spinal injuries (neurogenic overactive). Strips of isolated detrusor muscle
      were mounted in physiological Krebs-bicarbonate solution and cumulative
      concentration-response curves to 1 nM to 300 microM neurokinin A (NKA) were
      obtained in the absence and presence of neurokinin receptor antagonists, either
      the NK2 receptor-selective antagonist SR 48968 or the NK3 receptor-selective
      antagonist SB 223412. RESULTS: NKA evoked concentration-dependent contraction of
      normal, idiopathic, and neurogenic overactive detrusor strips. In idiopathic
      overactive detrusor muscle, NKA-induced contraction was significantly reduced
      relative to normal detrusor (0.031 +/- 0.005 mg/g, n = 11 versus 0.193 +/- 0.039
      mg/g, n = 7). Sensitivity to the peptide was also significantly (p < 0.01)
      reduced in idiopathic overactive detrusor, with mean pEC50 values (concentration
      producing 50% maximal response) of 6.62+/-0.16 (n = 11) compared to 7.47+/-0.19
      (n = 7) in normal detrusor. In contrast, NKA-induced responses of neurogenic
      overactive detrusor were similar to those in normal detrusor, with a mean maximum
      contraction of 0.199 +/- 0.036 mg/g (n = 10) and mean pEC50 value of 7.85+/-0.16
      (n = 10). NKA curves in all groups were shifted to the right by the NK2 receptor
      selective antagonist SR 48968 with high affinity, pK(B) values being similar in
      normal, idiopathic, and neurogenic overactive detrusor (8.85 + 0.08, n = 14; 8.97
      +/- 0.13, n = 12; 8.73 +/- 0.12, n = 8, respectively). In contrast the NK3
      receptor-selective antagonist SB 223412 had a minimal effect on NKA responses and
      affinity values were low (pK(B) 5.81 +/- 0.11, n = 12 in normal; 5.75 +/- 0.08, n
      = 12 in idiopathic overactive, and 5.77 +/- 0.13, n = 11 in neurogenic
      overactive). CONCLUSION: These data indicate that NKA-induced responses are
      impaired in detrusor muscle from idiopathic overactive human bladder, but not in
      detrusor muscle from neurogenic overactive bladder. The NK2 receptor subtype
      appears to mediate NKA responses in the normal, idiopathic overactive, and
      neurogenic overactive detrusor. This is important evidence suggesting a
      difference between the bladder pathophysiology observed in idiopathic versus
      neurogenic overactive detrusor.

PMID- 16420970
TI  - Epididymal SPAM1 and its impact on sperm function.
AB  - The most widely conserved mammalian sperm antigen is sperm adhesion molecule 1,
      SPAM1/PH-20, which is also the major testicular hyaluronidase. This
      multifunctional glycosyl phosphatidylinositol (GPI)-linked protein plays several
      roles in fertilization and is encoded by a gene that resides among hyaluronidase
      family members in a cluster on human 7q31/mouse 6A2. In the human cluster, SPAM1
      is the only functional hyaluronidase and of all six hyaluronidases in the genome
      it is the best characterized, both structurally and functionally. While SPAM1
      transcripts are abundantly expressed only in the testis, specifically in
      spermatids, the RNA and protein are present in the male reproductive tract and
      accessory organs and in the female tract of mice. Our investigation of the post
      testicular expression of SPAM1 shows that the protein is widely expressed in the
      epididymis. Like testicular SPAM1, epididymal SPAM1 (ES) has hyaluronidase
      activity and is conserved in at least five species (mouse, rat, bull, macaque,
      and human) all of which have putative androgen response elements in the gene
      promoters, consistent with androgen regulation. Testicular lumicrine factors have
      also been implicated in ES regulation. Based on regional expression, the protein
      is likely to play a role in both sperm maturation and storage. A minor secretory
      glycoprotein, ES is present in the epididymal luminal fluid in both a soluble and
      insoluble form (epididymosomes), with the latter having an intact lipid anchor.
      Genetic approaches have provided evidence for sperm uptake of ES in vivo, and in
      vitro uptake has been demonstrated with the use of Spam1 null mice. In vitro
      acquisition of ES on the sperm surface results in a pattern that mimics the wild
      type distribution. More importantly it significantly increases the ability of
      null sperm to penetrate the cumulus of oocytes via hyaluronidase activity,
      directly relating ES uptake with fertilizing ability and indicating that ES is a
      marker of sperm maturation.

PMID- 16420971
TI  - Regulation of baboon fetal ovarian folliculogenesis by estrogen.
AB  - Although it is well established that formation of the pool of follicles available
      for ovarian function and fertility in adulthood in human and non human primates
      occurs in utero, our understanding of the regulation of fetal ovarian development
      is incomplete. Our laboratories have been instrumental in establishing the baboon
      as a model for the study of human reproductive endocrinology and showed that
      estrogen plays a central integrative role in regulating fetal-placental
      development. Therefore, we adapted our baboon model to study the role of estrogen
      on fetal ovarian development. Estrogen receptors alpha and beta were expressed in
      pregranulosa cells and interfollicular nests of the baboon fetal ovary. In
      baboons in which estrogen levels had been suppressed by administration of an
      aromatase inhibitor throughout the second half of gestation, fetal ovarian
      follicle numbers were reduced by 50%, whereas the number of interfollicular nests
      comprised of oocytes and pregranulosa cells was increased. The decrease in
      follicles in estrogen-deprived animals was associated with a marked upregulation
      of expression of alpha-inhibin, but not activins or activin receptors and
      signaling molecules. Moreover, the majority of the follicles formed in ovaries of
      estrogen-depleted fetuses appeared unhealthy and contained oocytes with a marked
      reduction/depletion in microvilli, structures essential for uptake of substrates
      from surrounding granulosa cells. We propose that estrogen regulates fetal
      ovarian folliculogenesis and formation of healthy oocytes by controlling the
      intraovarian activin:inhibin ratio and the development of oocyte microvilli.
      These findings demonstrate a need for translational research studies of the
      impact of impairment of estrogen action/availability on reproductive function in
      adulthood.

PMID- 16420972
TI  - Membrane steroid receptor signaling in normal and neoplastic cells.
AB  - Rapid, non-genomic, steroid actions have been identified for more than 20 years.
      In the last decade however, a great expansion of research was observed. In the
      present review we report the identification and the subsequent signaling cascades
      involved in these rapid steroid effects. In the current state of knowledge, with
      the exception of progesterone for which a seven-loop G protein-coupled receptor
      has been identified, two major lines of evidence exist for membrane-related
      steroid actions: (1) a binding to the intracellular receptor, coupled to the
      plasma membrane, or interacting with other growth factor receptors, and (2) the
      existence of specific membrane steroid receptors. In addition, major
      intracellular signaling cascades involved in cell survival and/or apoptosis are
      activated by non-genomic steroid actions. Finally, it appears that cancer cells
      and tumors express membrane steroid sites, related to cancer aggressiveness.
      These lines of evidence may implicate, in the forthcoming years, membrane steroid
      receptors in cancer control as major or adjuvant chemotherapeutic agents,
      providing new possible targets for cancer chemotherapy.

PMID- 16420973
TI  - The influence of familiarity on brain activation during haptic exploration of 3-D
      facemasks.
AB  - Little is known about the neural substrates that underlie difficult haptic
      discrimination of 3-D within-class object stimuli. Recent work [A.R. Kilgour, R.
      Kitada, P. Servos, T.W. James, S.J. Lederman, Haptic face identification
      activates ventral occipital and temporal areas: an fMRI study, Brain Cogn. (in
      press)] suggests that the left fusiform gyrus may contribute to the
      identification of facemasks that are haptically explored in the absence of
      vision. Here, we extend this line of research to investigate the influence of
      familiarity. Subjects were trained extensively to individuate a set of facemasks
      in the absence of vision using only haptic exploration. Brain activation was then
      measured using fMRI while subjects performed a haptic face recognition task on
      familiar and unfamiliar facemasks. A group analysis contrasting familiar and
      unfamiliar facemasks found that the left fusiform gyrus produced greater
      activation with familiar facemasks.

PMID- 16420974
TI  - Vertical transmission of American foulbrood (Paenibacillus larvae) in honey bees
      (Apis mellifera).
AB  - The mode of transmission between hosts (horizontal versus vertical) of disease
      agents is important for determination of the evolution of virulence in pathogens.
      For disease management, it is imperative that the epidemiology of the disease is
      understood and pathogen transmission rates between hosts is a key factor for this
      understanding. Surprisingly little is known about transmission rates in honey bee
      pathology. We have studied the rate of vertical transmission of Paenibacillus
      larvae, the causative agent of American foulbrood (AFB) in honey bee colonies, as
      colonies reproduce by colony fission (swarming), by culturing for the spores from
      repetitive samples of adult bees. The results demonstrate vertical pathogen
      transmission to daughter swarms. The spore density declines over time in both
      mother colonies and daughter swarms if mother colonies do not exhibit clinical
      disease symptoms. Occasional positive samples more than a year post swarming,
      also in daughter swarms, indicate production of infectious spores from diseased
      larvae, without clinical disease observable by beekeepers, and/or maintenance of
      infective spores in the hive environment, allowing both horizontal and vertical
      transmission to be maintained. The results suggest that the virulence of AFB,
      being lethal at colony level in contrast to other bee diseases shaped by
      evolution, could be dependent on apicultural practices and that the pathogen
      probably would be maintained without causing frequent colony mortality in a
      natural system.

PMID- 16420975
TI  - Hearing assessment in pre-school children with speech delay.
AB  - OBJECTIVE: The purpose of this study was to detect any underlying hearing loss
      among the healthy pre-school children with speech delay. METHODS: 76 children,
      aged from 1 to 5 years, underwent a thorough audiological examination consisting
      of tympanometry, free field testing, otoacoustic emission recordings and auditory
      brainstem responses (ABRs). If hearing was normal, then they were evaluated by a
      child neurologist-psychiatrist. RESULTS: According to our findings, the children
      were classified into 3 groups; those with normal hearing levels (group I, 52
      children, 68.4%), sensorineural hearing loss (group II, 22 children, 28.9%) and
      conductive hearing loss (group III, 2 children, 2.6%). In group I, speech delay
      was attributed to pervasive developmental disorder (PDD), which represents high
      functioning autistic children (37 cases). Other causes were specific language
      impairment (SLI)-expressive (3 cases), bilingualism (2 cases), and unknown
      etiology (10 cases). More than half (59%) of the children diagnosed with PDD
      evidenced significant language impairment limited to more than two words.
      Children with SLI-expressive and bilingualism used a maximum of two words. In
      group II, 13 children suffered from profound hearing loss in both ears, 3 from
      severe, 3 had profound hearing loss in one ear and severe in the other, 2 from
      moderate, and 1 had moderate in one ear and severe in the other. No child had
      mild sensorineural hearing loss. The children with profound hearing loss in at
      least one ear had total language impairment using no word at all (10 cases), or a
      maximum of two words (6 cases). When hearing loss was moderate to severe, then
      the speech vocabulary was confined to several words (more than two words-6
      cases). Only two children suffering from conductive hearing loss both presented
      with complete lack of speech. CONCLUSION: A great number of healthy pre-school
      children with speech delay were found to have normal hearing. In this case, the
      otolaryngologist should be aware of the possible underlying clinical entities,
      especially of psychiatric nature. The children with profound sensorineural
      hearing loss exhibited more severe speech delay than those with moderate to
      severe. Regardless of etiology, the early identification and intervention
      contribute to positive outcome in this critical period of childhood for language
      development.

PMID- 16420976
TI  - In vitro exposure of community-associated methicillin-resistant Staphylococcus
      aureus (MRSA) strains to vancomycin: does vancomycin resistance occur?
AB  - Vancomycin is the preferred parenteral antibiotic for the treatment of all
      methicillin-resistant Staphylococcus aureus (MRSA) infections, including the
      newly emerging community-associated MRSA (CA-MRSA) infections. Vancomycin
      intermediate nosocomial MRSA strains have developed in vitro and in vivo after
      exposure to vancomycin. The aim of this study was to determine whether daily
      serial passage of CA-MRSA strains onto vancomycin-supplemented agar selects for
      the development of vancomycin resistance. Twelve clinical isolates of the six
      commonest Australian and US strains of CA-MRSA were serially passaged daily for
      25 days onto brain-heart infusion agar plates supplemented with 4 microg/mL
      vancomycin and then subcultured for a further 15 days onto antibiotic-free agar
      to assess the stability of the resistance phenotype. Minimum inhibitory
      concentrations (MICs) were determined by standard Etest every 5 days from day 0
      to day 40. Serial passaging resulted in increased MICs in all strains but the
      rises were modest, with an increase of < 2 doubling dilutions. All strains
      remained vancomycin susceptible throughout the experiment according to Clinical
      Laboratory Standards Institute criteria.

PMID- 16420977
TI  - Extracellular biosynthesis of silver nanoparticles using the fungus Aspergillus
      fumigatus.
AB  - Development of reliable and eco-friendly process for synthesis of metallic
      nanoparticles is an important step in the filed of application of nanotechnology.
      One of the options to achieve this objective is to use natural processes such as
      use of biological systems. In this work we have investigated extracellular
      biosynthesis of silver nanoparticles using Aspergillus fumigatus. The synthesis
      process was quite fast and silver nanoparticles were formed within minutes of
      silver ion coming in contact with the cell filtrate. UV-visible spectrum of the
      aqueous medium containing silver ion showed a peak at 420 nm corresponding to the
      plasmon absorbance of silver nanoparticles. Transmission electron microscopy
      (TEM) micrograph showed formation of well-dispersed silver nanoparticles in the
      range of 5-25 nm. X-ray diffraction (XRD)-spectrum of the silver nanoparticles
      exhibited 2theta values corresponding to the silver nanocrystal. The process of
      reduction being extracellular and fast may lead to the development of an easy
      bioprocess for synthesis of silver nanoparticles.

PMID- 16420978
TI  - Anxiety-mediated gait adaptations reduce errors of obstacle negotiation among
      younger and older adults: implications for fall risk.
AB  - The purpose of this study was to determine if anxiety-mediated gait adaptations
      can reduce the risk for falling among younger and older adults. Fourteen younger
      adults (23.14+/-3.08 years) and 14 older adults (69.28+/-5.41 years) participated
      in this study. Participants were asked to walk the length of a 7.20m walkway and
      avoid contact with an obstacle that appeared suddenly underfoot at either 25% or
      75% of the gait cycle duration. Testing was conducted in four conditions of
      postural threat. The obstacle was presented as a light beam and did not
      jeopardize balance when contacted. Fall risk was inferred from the frequency of
      obstacle contacts. Our findings indicated that obstacle contact frequency
      decreased when conservative gait patterns emerged. These findings imply that
      anxiety-mediated gait adaptations are beneficial in reducing the risk for falling
      among older adults and present the possibility that fear of falling may offer
      protective benefits for postural control. One possibility is that the beneficial
      effects of anxiety can only be realized among older adults who do not fear
      falling.

PMID- 16420980
TI  - Anti-platelet activity of KR-32560, a novel sodium/hydrogen exchanger-1
      inhibitor.
AB  - We investigated the anti-platelet effect of a newly synthesized guanidine
      derivative KR-32560, a sodium/hydrogen exchanger-1 (NHE-1) inhibitor, together
      with the elucidation of the possible mode of action. KR-32560 concentration
      dependently inhibited the aggregation of washed rabbit platelets induced by
      collagen (10 microg mL(-1)) and arachidonic acid (AA; 100 microM), with IC50
      values of 25 and 46 microM, respectively. Whereas, KR-32560 showed weaker potency
      against aggregation induced by thrombin (0.05 UmL(-1)) and U46619 (1 microM), and
      had no effect on thapsigargin (0.5 microM)- or A23187 (5 microM)-induced platelet
      aggregation up to 50 microM. KR-32560 inhibited the collagen-induced [3H]AA
      liberation in a concentration-dependent manner. In addition, KR-32560
      significantly suppressed TXB2 formation in AA-exposed platelets, but had no
      effect on production of PGD2, indicating an inhibitory effect on TXA2 synthase.
      This finding was supported by a TXA2 synthase assay that KR-32560 inhibited the
      conversion of PGH2 into TXB2 with a similar magnitude to suppression of TXB2
      formation. Furthermore, KR-32560 significantly inhibited the collagen-induced
      [Ca2+]i mobilization and serotonin secretion. Taken together, these observations
      suggest that the anti-platelet activity of KR-32560 may be mediated by the
      inhibition of cytoplasmic Ca2+ mobilization and AA liberation.

PMID- 16420979
TI  - Fenofibrate treatment reduces circulating conjugated diene level and increases
      glutathione peroxidase activity.
AB  - AIMS: Treatment with fibrates showed benefit in randomized trials predominantly
      in subgroups of patients with dyslipidaemia of metabolic syndrome. Post hoc
      analyses of these trials show that the effect of fibrates on lipid levels
      explains only minor part of the treatment benefit. The aim of the present study
      was to examine effect of fenofibrate on some parameters of oxidative stress.
      PATIENTS AND METHODS: The study group included 20 patients (6 males, 14 females)
      with combined dyslipidaemia. The average age was 54+/-10 years. Fenofibrate was
      given for 8 weeks in the dose of 300 mg daily. Lipid levels and parameters of
      oxidative stress were measured at baseline and after treatment period. RESULTS:
      Treatment with fenofibrate led to reduction of total cholesterol by 18%, LDL
      cholesterol and apoB by 17%, triglycerides by 46%, as well as increase of HDL
      cholesterol level by 10%. Among the measured parameters of oxidative stress,
      fenofibrate treatment significantly reduced level of circulating conjugated
      dienes (CD) in average by 42% (p < 0.0001) and also non-significantly reduced the
      production of malonaldehyde. Fenofibrate treatment led to an increase of the
      activity of antioxidant enzyme glutathione peroxidase (GPx) by 80% from baseline
      values (p = 0.001). CONCLUSION: Treatment with fenofibrate significantly reduced
      the level of conjugated dienes, a measure of LDL oxidation, and increased GPx
      activity. This finding could at least partially explain beneficial effect of
      fenofibrate treatment beyond that related to levels of commonly measured lipid
      parameters.

PMID- 16420981
TI  - Chronic inflammation, immunosuppression and cancer: new insights and outlook.

PMID- 16420982
TI  - Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an
      open label study.
AB  - PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as
      either 'de novo' (monotherapy) or 'add-on' therapy in patients with different
      generalised epilepsies characterised by myoclonic seizures from an observational
      study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with
      different types of generalised epilepsies (juvenile myoclonic epilepsy (JME),
      severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS),
      myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic
      epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes).
      Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency
      changes and adverse events were observed. Follow-up was conducted for a period of
      12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de
      novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients
      achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved
      seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure
      frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or
      seizure worsening. Not even a single patient discontinued due to adverse effects.
      CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on
      therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic
      seizure frequency in patients with generalised epilepsy. LEV was also well
      tolerated.

PMID- 16420983
TI  - Roles of glia in the Drosophila nervous system.
AB  - Glial cells have diverse functions that are necessary for the proper development
      and function of complex nervous systems. Various insects, primarily the fruit fly
      Drosophila melanogaster and the moth Manduca sexta, have provided useful models
      of glial function during development. The present review will outline evidence of
      glial contributions to embryonic, visual, olfactory and wing development. We will
      also outline evidence for non-developmental functions of insect glia including
      blood-brain-barrier formation, homeostatic functions and potential contributions
      to synaptic function. Where relevant, we will also point out similarities between
      the functions of insect glia and their vertebrate counterparts.

PMID- 16420984
TI  - Quantum cascade laser-based photoacoustic spectroscopy of volatile chemicals:
      application to hexamethyldisilazane.
AB  - The use of photoacoustic spectroscopy and mid-infrared quantum-cascade lasers
      (QCLs) for the detection of hexamethyldisilazane (HMDS) is reported. A detection
      limit of 200 parts in 10(9) is found using a Fabry-Perot QCL operated at 8.4
      microm in pulsed mode and a photoacoustic cell equipped with four electret
      microphones. The laser multimode spectrum matches the range of the N-H bending
      absorption band of HMDS. Further improvements to reach lower detection limits are
      discussed.

PMID- 16420985
TI  - Multiplexed PCR genotyping of HPVs from plantaris verrucae.
AB  - BACKGROUND: Plantaris verrucae are a common diagnosis in childhood, consume a
      significant amount of health-care resources, have many painful treatment options
      and many recurrences. OBJECTIVES: The objective of this study was to design and
      test a single site-anchored, multiplexed and expandable PCR assay for common
      types of cutaneous HPVs. STUDY DESIGN: Common forward and unique reverse primers
      were selected from the E2 open reading frames of five cutaneous HPV genotypes.
      These were analyzed for sensitivity and selectivity using pHPV plasmids and
      several control DNAs in an optimized multiplexed assay. This standardized assay
      was used to analyze human verruca plantaris tissue for genome type and to
      evaluate the effect of a commonly used treatment protocol. RESULTS: A sensitive,
      multiplexed PCR assay for human cutaneous HPV genotypes 1a, 2a and 4 was
      developed. Specific-unique primers and a consensus anchor primer were selected
      within the HPV E2 region to produce amplicons varying by greater than 100bp. In
      analytical sensitivity studies, fewer than 100 genome copies of HPV1a and 2a were
      detected, and fewer than 1000 copies of HPV4 were detected. The multiplexed assay
      did not amplify regions of human placenta, calf thymus, CaSki or SiHa DNA and E.
      coli, pBR322 or non-HPV virus DNAs. In combination with a forensic DNA extraction
      procedure, the multiplexed HPV assay detected and identified HPV types in 23 of
      51 (45%) deep plantaris verrucae. Two patients were found with two different
      genotypes in single deep plantaris verruca. Detection of the HPV genome was
      followed as a function of tissue ablation and Mediplast treatment in one patient.
      In healing tissue, the genome content was reduced but had not totally
      disappeared. CONCLUSIONS: The multiplexed HPV assay can be used to determine
      genotype prevalence that may correlate with treatment efficacy.

PMID- 16420986
TI  - [Acquired mutation of JAK2 tyrosine kinase and polycythaemia vera].
AB  - Polycythaemia vera is an acquired myeloproliferative disorder characterised by a
      polycythaemia resulting of a clonal disorder arising in a multipotent
      hematopoietic stem cell. The increase of red cell mass exposes to a high risk of
      arterial or venous thrombosis and thus requires a cytoreductive treatment. An
      acquired genetic mutation in exon 12 of the JAK2 tyrosine kinase gene, leading to
      a substitution of a valine to a phenylalanine (V617F), has been described in most
      polycythaemia vera patients. This mutation increases the phosphorylation activity
      of JAK2, promotes the spontaneous cellular growth and induces erythrocytosis in a
      mouse model. Prevalence studies of V617F JAK2 mutation in different
      myeloproliferative disorders have found this genetic alteration in half of
      idiopathic myelofibrosis and in one third of essential thrombocythaemia. This
      finding is a huge progress in the understanding of polycythaemia vera
      physiopathology, it will be also an useful tool for the diagnosis of
      myeloproliferative disorders and it opens a new field for the development of
      targeted therapeutic approaches in these disorders.

PMID- 16420987
TI  - [Ac-SDKP, a marker of the angiotensin-converting enzyme activity?].
AB  - The tetra-peptide Acetyl-Ser-Asp-Lys-Pro (Ac-SDKP) generated by the cleavage of
      thymosine beta4 inhibits the proliferation of hematopoietic stem cells and the
      proliferation and secretion of fibroblasts in the myocardium and the glomeruli.
      The clinical administration of Ac-SDKP has been proposed and partially
      investigated. The peptide could protect hematopoietic stem cells during anti
      neoplastic treatments leaving cancerous cells unprotected. As it opposes the
      effects of TGFbeta it could prevent fibrosis after myocardial infarcts and
      glomeruli fibrosis during the natural course of diabetic nephropathy. However,
      until now the expected benefits of such a treatment are based on an indirect
      consideration. Indeed, the degradation of Ac-SDKP is due to the action of the
      angiotensin-converting enzyme. Interestingly, the blocking of this enzyme both
      improves the above-mentioned fibrosis and increases the plasma levels of Ac-SDKP.
      Should the therapeutic effects prove solid, and therapeutic levels be established
      assaying Ac-SDKP could be an interesting marker of therapeutic efficiency.

PMID- 16420988
TI  - [Normal and abnormal cytological aspects of peripheral blood cells in neonates
      and young children].
AB  - Morphological alterations of blood cells are observed early in most hereditary
      disorders. Therefore, the cytological study of the blood cells is a must for the
      diagnosis of these disorders in neonates and children. Knowledge of the
      quantitative and qualitative physiological peculiarities of blood cells in
      neonates is mandatory for an accurate interpretation. In the present article, the
      main cytological characteristics of blood cells in healthy neonates and infants
      and their abnormalities associated with hereditary or acquired blood disorders
      are reviewed.

PMID- 16420989
TI  - [Beta-lactamases of Gram negative bacteria: never-ending clockwork!].
AB  - The acquired resistance against the wide-spectrum and highly stable beta-lactams
      including third-generation cephalosporins (3GC) and carbapenems is constinuously
      increasing and widespead with the discovery of various plasmid-encoded, or genes
      cassette or integrons coding for a novel beta-lactamase, always a major mechanism
      of resistance. To explain resistance against 3GC, with the continuing story with
      TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M
      type, at least CTX-M-40, but also other non predominant types intitled BES, GES,
      PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase
      inhibitor is correlated to synthesis of transferable cephalosporinases (class C)
      usually located in the chromosome but mobilized from Enterobacter spp.,
      Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such
      genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX
      group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem
      originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii
      and finally to enterobacteria is related to production of novel enzymes (classes
      B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of
      evolution towards more and more resistance is given by Salmonella, even from
      animal origins, a great threat fo public health. So far it appears necessary to
      perform molecular approaches to identify such enzymatic production. Finally
      because the absence of real new drugs, the discovery of some progenitors of the
      gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide
      not only in medecine or veterinary field but also in agriculture, including
      aquaculture for example.

PMID- 16420990
TI  - [Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies
      in a Moroccan patient].
AB  - The oculo-cerebro-renal syndrome of Lowe is a rare X-linked disorder, caused by
      the inositol biphosphate 5-phosphatase deficiency, localized to the Golgi
      complex. Several mutations were reported in patient's OCRL gene leading to enzyme
      deficiency. We report a Moroccan case of OCRL syndrome of Lowe with a neo
      mutation in exon 10. The patient aged of 19 months was referred to our medical
      centre because of a psychomotor retardation. He had a medical history of eye
      abnormalities including cataract and bilateral glaucoma, diagnosed when he was 5
      weeks old. Cataract has been treated after chirurgical therapy but ocular
      hypertonia persisted. Physical examination revealed an axial hypotonia and
      walking difficulties. Laboratory tests revealed a moderate acidosis (20 mmol/L),
      a slight decrease of serum phosphate level (24 mg/L) and an increased serum
      phosphatase activity. Further studies showed mild proteinuria, urinary
      bicarbonates loosing and generalised hyperaminoaciduria. Based on both clinical
      and biological data, Lowe syndrome has been suggested. In this context, molecular
      investigation has been performed using dHPLC/sequencing techniques which allow
      identifying an original mutation c.776T>C (p.Phe259Ser), localized on the exon 10
      of the OCRL gene. The mutation was not found in the probant's mother suggesting a
      neo mutation. Lowe syndrome is a rare hereditary X-linked disorder resulting from
      a variety of heterogeneous mutations of OCRL gene. Indeed, numerous mutations
      have been reported, variations were noted concerning their localization as well
      as their type. To our knowledge, this is the first report of the neo mutation
      c.776T>C of OCRL gene and the first published case report of the Lowe syndrome in
      a Moroccan patient.

PMID- 16420991
TI  - [Molecular identification of species within the Mycobacterium tuberculosis
      complex using regions of difference].
AB  - The differentiation within the Mycobacterium tuberculosis complex (MTBC) based on
      phenotypic methods is long and does not give an unambiguous result in every case
      whereas the advance in genetic knowledge leads to new views. Thus, regions of
      difference (RD), that seem to characterize the species of the MTBC, have been
      identified. Amplification methods, targeted on these zones, have been developed
      then. The study of four regions (RD1, RD5, RD9, RD10) has been done on 64
      isolates formerly identified thanks to phenotypic methods. Genotypic results
      confirm phenotypic identifications except in one case. This strain initially
      identified as M. tuberculosis and isolated from a Gabonese patient, corresponds,
      according to genotypic identification, to M. africanum. Since phenotypic
      characterization of M. africanum is difficult, this method would allow to
      accurately determine the true prevalence of this specie. Moreover, the study of
      RD10 doesn't seem to be informative. The amplification of only two RD, RD1 and
      RD9 carries out the identification of all M. tuberculosis and M. bovis BCG
      isolates. M. bovis and M. africanum will be then identified thanks to RD5. Thus,
      this easy and rapid method of identification of the major species of MTBC seems
      to be appropriated for a routine use.

PMID- 16420992
TI  - [Adaptation of Biomerieux enzymatic UV ammonia on Konelab analysers].
AB  - INTRODUCTION: Circulating ammonia in normal patients is relatively low, despite
      the fact that ammonia is continually produced from endogenous amino acid
      metabolism. The physiopathological interest of plasmatic ammonia determination
      lies primarily in its relationships to hepatic insufficiency (cirrhotic or
      neoplasic), or the diagnosis and the forecast of the Reye's syndrome. OBJECTS:
      This study describes an evaluation of plasmatic ammonia determination by the UV
      end point enzymatic method using GLDH on KONELAB(TM) analyzers. METHODS: The
      glutamate dehydrogenase (GLDH : EC.1.4.1.3) catalyses the reducing amination of
      alpha-cetoglutarate in the presence of NH(4)(+) and of NADPH, H(+) to form
      glutamate and NADP(+). The reduction of NADPH,H(+)'s concentration, directly
      proportional to ammonia rates, is evaluated at 340 nm. All the conditions were
      met to optimize the method, while covering a satisfying field of measurement.
      RESULTS AND COMMENTS: The evaluation of the modified method showed a good
      precision (repeatability: CV < 4 %; interserial reproducibility: CV from 2.01 to
      2.93 %; Intraserial reproducibility: CV equal to 0.67%) and a very good accuracy.
      The field of measurement extends from 27 to 250 micromol/L, with a limit of
      detection (L(D)) lowered to 0.325 micromol/L. CONCLUSION: The adapted technique
      is simple, fast, inexpensive and especially automatizable. It is in addition
      reliable and chiefly more sensitive, adapting particularly to the determination
      of plasmatic ammonia in urgency as in routine within our laboratory.

PMID- 16420993
TI  - [Waldenstrom's macroglobulinemia with an uncommon presentation].
AB  - Waldenstrom's macroglobulinemia is a rare disease with an indolent clinical
      course. The median age of the affected patient is 65 years. Nevertheless, we
      report a case of Waldenstrom's macroglobulinemia revealed by a splenomegaly and
      severe pancytopenia, in a 51-year-old man without previous medical history.
      According to the recent consensus recommendations for the clinicopathological
      definition of Waldenstrom's macroglobulinemia, diagnosis was made through
      morphological and immunophenotypic data of medullary cells. The reduced survival
      of the patient is associated with the importance of the cytopenia.

PMID- 16420994
TI  - [Evaluation of the reality of capillary glycemia measurement in an intensive care
      unit].
AB  - BACKGROUND: The usual glycemic supervision based on repeated measures of the
      capillary glycemia with the strip of which reliability can be taken at fault
      especially in critically ill patients. The objective of this work was to evaluate
      the reliability of capillary glycemia measurement in intensive care unit.
      MATERIAL AND METHODS: [corrected] The study was performed in a medical intensive
      care unit, during six months (July to December 2004). The capillary glycemias
      were carried out with only one blood glucose monitor and were compared with the
      referenced glycemias. The correlation between two methods was carried out by the
      parametric Pearson coefficient. The error percentage of the blood glucose monitor
      was calculated. The agreement of two methods was evaluated by Bland and Altman
      test. RESULTS: Were performed 245 glycemic pairs for 198 patients, their mean age
      was 42.6 +/- 14.6 years, 30(15%) among them were diabetics. The referenced
      glycemia was 8.7 +/- 5.5 mmol/L and the capillary glycemia was 8.3 +/- 4.6
      mmol/L. The correlation coefficient was 0.97 (p<0.001); 56 percent of the values
      had an error percentage lower than 10, 27 percent between 10 and 20%, and there
      were 17 percent discordant values with an error percentage higher than 20. The
      method of Bland and Altman objectived a skew of 0.40 mmol/L and a bad precision
      of +/- 2.90 mmol/L. CONCLUSION: The reliability of capillary glycemias was not
      satisfactory with bad precision and high percentage of discordance. The capillary
      glycemias must be interpreted with precaution in intensive care unit.

PMID- 16420995
TI  - [Numerical help to bacterial identification: definition of a first kind error
      risk].
AB  - The numerical method commonly used as an help to the bacterian identification
      appears quite efficient in its first role, i.e. to propose the name of the
      plausible bacteria, but it fails to define a confidence level to be assiociated
      to the final decision. To correct this, this paper propose to calculate the
      response probability distribution for each possible bacteria. The calculation
      uses the so-called "Monte-Carlo" method and has to be performed once for all on a
      given set of biochemical tests. For each calculated ditribution, it is easy to
      find a first kind error risk, or alpha-error risk. The proposed theoretical
      approach moreover avoid the comparison of "identification scores", which is
      always questionable so far the various bacteria present very different
      sensitivities to the biochemical tests.

PMID- 16420996
TI  - [Evaluation of the analytical performance of the ImmunoCap 250 (Sweden
      Diagnostics)].
AB  - A new automate, ImmunoCap 250 has recently been released by Sweden Diagnostics
      for the determination of specific and total IgE. We have evaluated its analytical
      performances (intra- and inter-assay precision, linearity, recovery and
      sensibility) and compared the results obtained by Unicap 100 on 149 samples
      positive for 12 different allergens and 30 samples containing different
      concentrations of total IgE. Intra- and inter-assay precision are less than 10%
      excepted for the specific IgE of one allergen (i3, common wasp), but still in
      accordance with the NCCLS guidelines. The sensibility is 0.01 kU(A)/L for
      specific and 0.35 kU/L for total IgE. The method is linear up to 5000 kU/L for
      total and at least 80 kU(A)/L for specific IgE. The recovery test showed a
      recovery of the International standard WHO 75/502 between 85 and 115%, with a
      mean of 103%. The correlation coefficient between the ImmunoCap 250 and Unicap
      100 is 0.9866 and 0.9984 for specific and total IgE respectively. ImmunoCap 250
      is a good solution for laboratories that perform twenty to thirty thousand
      determinations.

PMID- 16420997
TI  - Seven-day viable analysis of some ophthalmic preparations with different
      concentrations of benzalkonium chloride.
AB  - The efficacy of zinc sulphate and boric acid ophthalmic preparations, containing
      benzalkonium chloride as preservative have been investigated against Gram
      negative Escherichia coli and Pseudomonas aeruginosa and Gram-positive
      Staphylococcus aureus bacteria. The viability of bacteria was checked after 7
      days though they were completely suppressed after 24 hours of inoculation. Zinc
      sulphate increased the antimicrobial activity of benzalkonium chloride, whereas
      the boric acid or its combination with zinc sulphate reduced the same. The
      Pseudomonas aeruginosa was found to be viable against zinc sulphate, boric acid
      or its combination at a concentration of 0.01% to 0.005% of the preservative.
      Escherichia coil and Staphylococcus aureus also exhibited resistance but to a
      lesser extent than Pseudomonas aeruginosa. This viability may be dangerous in
      case of multidose ophthalmic preparations.

PMID- 16420998
TI  - A study of effects of harmidine on C.N.s. Of animals.
AB  - Effect of various doses of harmidine, a harmala alkaloid were evaluated on
      voluntary motor activity of rats, and on normal body temperature of mice. It was
      observed that harmidine antagonised the motor activity decreasing, Ptosis and
      miosis producing and hypothermic effects of reserpine like M.A.O. Inhibitors, as
      well as it prevented these effects of reserpine through a direct stimulant effect
      like amphetamine and imipramine. Further studies are suggested.

PMID- 16420999
TI  - An analysis of serum estradiol and serum progesterone in postmenopausal women of
      karachi suffering from breast cancer.
AB  - The cancer patients (39) and control (12) were subjected to postmenopausal
      hormonal evaluation in which serum estradiol and serum progesterone values were
      found to be 54.56 +/- 10.20 pg/ml as compared to 18.66 +/- 6.31 pg/ml and 0.170
      +/- 0.01 ng/ml as compared to 0.229 +/- 0.01 ng/ml respectively. Consequently it
      was inferred that in cancer postmenopausal patients when serum estradiol level
      increases the serum progesterone level decrease and vice versa.

PMID- 16421000
TI  - Fatty Acid compositions of two siphonaceous green algae from the coast of
      karachi.
AB  - Two green seaweeds Bryopsis pennata Lamour. and Valoniopsis pachynema (Mart.)
      Bthetarg. collected from the coast of Karachi have been studied for their fatty
      acid compositions. Altogether 34 fatty acids were identified as methyl esters
      from them, out of which 9 were saturated and 25 unsaturated acids including 17
      monoenoic, 5 dienoic and 4 trienoic acids. They were identified by gas
      chromatography-mass spectroscopy (GC-MS). Both seaweeds contained exactly the
      same saturated fatty acids, their unsaturated acids (67.58-71.81%) were greater
      in proportion than the saturated ones (28.17-32.38%). Tridecatrienoic (28.1%) and
      palmitic (13.93%) acids occurred in highest amount. Oleic acid was not uniformly
      present and occurred in small proportion (1.53%).

PMID- 16421001
TI  - Anodic voltammetric study of ascorbic Acid at platinum and gold rotating disc
      electrodes.
AB  - Anodic Voltammetry of ascorbic acid at platinum and gold rotating disc electrodes
      has been examined in acidic and alkaline media. Ascorbic acid is oxidised by a
      single two electron wave at platinum and one electron two step at gold electrode.
      The best medium for electroanalysis is 0.1 mol 1(-1) sulphuric acid in which it
      shows obedience to the Levich relationship at both electrodes. The limiting
      current is linearly proportional to ascorbic acid concentration with Zero
      intercept and shows excellent rapid voltammetric determination. Electrode Kinetic
      parameters for mass and charge transfer have been determined. Voltammetric method
      has been used to determine the number of electrons involved in the reaction and
      the reaction mechanism has been elucidated.

PMID- 16421002
TI  - Effects of drugs against cytotoxic compoundsfrom marine animals iv-hepatotoxic
      activity ofsea-snake hydrophis cyanocinctus venom.
AB  - Hepatotoxic activity and pathogenesis of sea snake Hydrophis cyanocinctus venom
      have been studied in guinea pigs and albino rats by histopathological examination
      and determining total Ca(2+). Concentration in liver tissue. Efficacy of two
      Ca(2+). antagonist drugs, verapamil and diltiazem was also studied against the
      cytotoxic activity of this venom. Administration of both lethal and sublethal
      doses of Hydrophis cyancinctus crude venom induced increased cellularity within
      the portal area in liver accompanied by increased tissue Ca(2+) concentration.
      This elicit a close correlation between tissue necrosis and increased Ca(2+)
      content in tissues. Both verapamil and diltiazem administration after an
      injection of H. cyanocinctus venom showed significant decrease in Ca(2+)
      concentration and tissue necrosis. Increase in survival time was also noted in
      almost all animals receiving Ca(2+) - antagonist drugs. It is thus suggested that
      cytotoxic compounds present in this marine venom cause tissue and cellular
      necrosis by increasing Ca(2+) influx within the cells which in turn stimulates
      Ca(2+) -dependent processes resulting in both organ dysfunction and sometimes
      fatality in few cases. But both these effects could be inhibited by using
      antagonizing drugs which could reduce the pathological conditions induced by such
      compounds by blocking the cation influx and its dependent processes.

PMID- 16421004
TI  - Amount of polyvinyl alcohol (pva) polymer adsorbed on the oil globules in liquid
      paraffinemulsions prepared by pva.
AB  - A modified method for estimating polyvinyl alcohol (PVA) in solution has been
      developed based on the principle of formation of PVA-iodine complex which has a
      characteristic absorption maxima. The amount of PVA adsorbed on the oil globules
      in liquid paraffin oil-water emulsions prepared by the polymer was determined.
      This was found to be dependent on the concentration of the polymer in the
      continuous phase of the emulsion until it reached a saturation point. Beyond that
      concentration, the amount of adsorption remained steady.

PMID- 16421003
TI  - Review article : stability and uses of liposomes.
AB  - The present article reviews information about the stability and uses of
      liposomes.

PMID- 16421005
TI  - Short note : concept and scope of community pharmacy.
AB  - Recognition of the importance of a Pharmacist in the rational use of drugs has
      been slow but is growing Public education in drug use is needed because without
      its recognition and proper utilization people lack the skills and knowledge which
      they require to make informed decisions about how to use drug (including when
      they should not be used) and to understand the role of a Pharmacist and drugs in
      health care.

PMID- 16421007
TI  - Helicobacter pylori-associated immune thrombocytopenia.
AB  - Idiopatic thrombocytopenic purpura (ITP), a disorder characterized by
      autoantibody-mediated platelet destruction, may be primary or secondary to
      various illnesses including lymphoproliferative, autoimmune, or infectious
      diseases. There are increasing data on the association between Helicobacter
      pylori infection and idiopathic thrombocytopenic purpura and the significant
      increase in platelet count after bacterial eradication. The aim of this review is
      to consider the studies so far published on Helicobacter pylori infection and
      idiopathic thrombocytopenic purpura in order to evaluate a possible pathogenic
      correlation between these two conditions. A review of the literature data show
      that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic
      purpura is effective in increasing platelet count in approximately half of the
      cases. However, since the studies so far published are few, sometimes
      controversial and involve small series of patients, further controlled studies on
      larger numbers of patients with longer follow-up are needed to confirm these
      preliminary findings.

PMID- 16421008
TI  - Platelet FcgammaRIIA expression is associated with the alpha2 integrin C807T gene
      polymorphism in type 2 diabetes.
AB  - "Patelet" FcgammaRIIA is stably overexpressed in type 2 diabetes and may also
      play a role in collagen-mediated platelet activation. Platelet surface integrin
      a(2)ss(1)-collagen interaction is an early step associated with platelet adhesion
      and activation and plays an important role in arterial thrombosis. The objective
      of this study was to characterize the relationship in diabetes and non-diabetes
      platelets between FcgammaRIIA expression and a polymorphism associated with
      arterial thrombotic events, polymorphism C807T on the gene encoding a(2)ss(1).
      Platelet flow cytometry and allele-specific PCR revealed a significant
      correlation in type 2 diabetes between low platelet FcgammaRIIA expression and
      the 807TT genotype that is associated with increased platelet a(2)ss(1) receptor
      density. We conclude that uni- or bi-directional modulation of surface expression
      may exist between the platelet FcgammaRIIA receptor and a a(2)ss(1) thrombogenic
      polymorphism that could play a role in platelet sensitivity to collagen in type 2
      diabetes.

PMID- 16421009
TI  - Ecto-nucleotide pyrophosphatase/phosphodiesterase as part of a multiple system
      for nucleotide hydrolysis by platelets from rats: kinetic characterization and
      biochemical properties.
AB  - In this study, we describe an ecto-nucleotide pyrophosphatase/phosphodiesterase
      (E-NPP) activity in rat platelets. Using p-nitrophenyl 5'-thymidine monophosphate
      (p-Nph-5'-TMP) as a substrate for E-NPP, we demonstrate an enzyme activity that
      shares the major biochemical properties described for E-NPPs: alkaline pH
      dependence, divalent cation dependence and blockade of activity by metal ion
      chelator. K(m) and V(max) values for p-Nph-5'-TMP hydrolysis were found to be 106
      +/- 18 microM and 3.44 +/- 0.18 nmol p-nitrophenol/min/mg (mean +/- SD, n = 5).
      We hypothesize that an E-NPP is co-localized with an ecto-nucleoside triphosphate
      diphosphohydrolase and an ecto-5'-nucleotidase on the platelet surface, as part
      of a multiple system for nucleotide hydrolysis, since they can act under distinct
      physiological conditions and can be differently regulated. Thus, 0.25 mM suramin
      inhibited p-Nph-5'-TMP, ATP and ADP hydrolysis, while 0.5 mM AMP decreased only p
      Nph-5'-TMP hydrolysis. Besides, 5.0, 10 and 20 mM sodium azide just inhibited ATP
      and ADP hydrolysis. Angiotensin II (5.0 and 10 nM) affected only ADP hydrolysis.
      Gadolinium chloride (0.2 and 0.5 mM) strongly inhibited the ATP and ADP
      hydrolysis. The E-NPP described here represents a novel insight into the control
      of platelet purinergic signaling.

PMID- 16421010
TI  - Effects of malondialdehyde content in low density lipoproteins on platelet
      adhesion.
AB  - Platelets play a key role in thrombotic vascular occlusion at the side of an
      atherosclerotic plaque. Malondialdehyde (MDA) derivatives are components of
      oxidized LDL. Recent studies suggest enhanced adhesion of platelets on oxidized
      LDL, but evidence of MDA-modified LDL contribution to enhanced platelet adhesion
      is missing. The aim of this study was to investigate platelet adhesion on LDLs
      with various content of MDA and to analyze its physiological relevance. LDLs were
      isolated by hydroxyapatite chromatography then analyzed. MDA, vitamin E and
      vitamin A content was estimated by HPLC methods and adhesion of platelets on
      modified LDLs was assessed. Both MDA and hypochlorite reactions induced an
      increase of both malondialdehyde content and negative charge in LDLs
      preparations. In LDLs of iron-overloaded patients both MDA content and negative
      charge was also significantly increased. The analysis of data showed that
      enhanced negative charge of LDLs had only negligible influence on platelet
      adhesion. The binding of platelets on LDL particles modified by MDA resulted in
      an S-shape curve and was substantially enhanced by high levels of MDA in LDL
      preparations. Malondialdehyde content both in hypochlorite modified LDLs and in
      LDLs of iron-overloaded patient matched the lower part of the binding curve. The
      platelet adhesion on circulating LDLs modified in in vivo conditions of oxidation
      stress in blood of iron-overloaded patients depends with considerable certainty
      preferably on non-MDA derived changes in derivatized LDLs. On the other hand,
      oxidized LDLs in atherosclerotic lesions can be much more extensively modified by
      MDA resulting in surfaces with enhanced affinity to adhering platelets. Such LDLs
      may be accessible to platelets, due to endothelial denudation or plaque rupture.

PMID- 16421011
TI  - Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular
      function in normal volunteers and patients with prior ischaemic stroke.
AB  - Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole
      inhibit platelets are well characterised, their effects on soluble modulators of
      thrombosis, inflammation, and endothelial function have yet to assessed
      systematically. In this investigation aspirin (A), clopidogrel (C), and
      dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD,
      CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and
      11 patients with previous ischaemic stroke. At the end of each treatment period
      plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1
      (MCP-1), nitric oxide metabolites (NO(x)), plasminogen activator inhibitor-1 (PAI
      1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and
      platelet derived growth factor (PDGF); were measured blinded to treatment.
      Dipyridamole reduced plasma vWf levels (%) in both volunteers, -10.0 (4.95), and
      patients, -10.11 (4.34) (p < 0.05). Dipyridamole also lowered CRP (mg/l) in
      patients, -0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in
      volunteers, -5.30 (2.20) (p < 0.05), and patients, -3.61 (2.75) (non-significant
      trend). Aspirin lowered PDGF (ng/ml) in volunteers, -3.46 (1.55), but not
      patients. Triple antiplatelet therapy was superior to dual and mono therapy in
      reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related
      effects on soluble modulators of thrombosis, inflammation, and endothelial
      function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers
      plasma PAI-1 levels. These effects may explain, in part, their roles in
      preventing atherothrombogenesis.

PMID- 16421012
TI  - Effect of combined administration of clopidogrel and lysine acetylsalicylate
      versus clopidogrel and aspirin on platelet aggregation and activated GPIIb/IIIa
      expression in healthy volunteers.
AB  - Platelet activation contributes to thrombotic events in cardiovascular disease.
      Acetylsalicylic acid (ASA) is used in combination with clopidogrel to reduce
      cardiovascular events. Lysine acetylsalicylate (L-ASA), also inhibits platelet
      activation with fewer gastrointestinal side effects than ASA. Dual therapy with L
      ASA and clopidogrel may result in an antiplatelet effect with fewer side effects.
      We compared the antiplatelet effect of combined ASA/clopidogrel versus L
      ASA/clopidogrel in healthy subjects. Fourteen volunteers (seven men and seven
      women, aged 25-45 years) received antiplatelet therapy during 14-day periods in
      the following sequence: 75 mg ASA; 160 mg L-ASA; 75 mg clopidogrel; 160 mg L-ASA
      plus 75 mg clopidogrel, and 75 mg ASA plus 75 mg clopidogrel. We evaluated
      platelet aggregation and glycoprotein IIb/IIIa activation. Our results show that
      administration of L-ASA/clopidogrel is as effective as ASA/clopidogrel
      combination.

PMID- 16421014
TI  - Glutathione-related enzymes and the eye.
AB  - Glutathione and the related enzymes belong to the defence system protecting the
      eye against chemical and oxidative stress. This review focuses on GSH and two key
      enzymes, glutathione reductase and glucose-6-phosphate dehydrogenase in lens,
      cornea, and retina. Lens contains a high concentration of reduced glutathione,
      which maintains the thiol groups in the reduced form. These contribute to lens
      complete transparency as well as to the transparent and refractive properties of
      the mammalian cornea, which are essential for proper image formation on the
      retina. In cornea, gluthatione also plays an important role in maintaining normal
      hydration level, and in protecting cellular membrane integrity. In retina,
      glutathione is distributed in the different types of retinal cells. Intracellular
      enzyme, glutathione reductase, involved in reducing the oxidized glutathione has
      been found at highest activity in human and primate lenses, as compared to other
      species. Besides the enzymes directly involved in maintaining the normal redox
      status of the cell, glucose-6-phosphate dehydrogenase which catalyzes the first
      reaction of the pentose phosphate pathway, plays a key role in protection of the
      eye against reactive oxygen species. Cornea has a high activity of the pentose
      phosphate pathway and glucose-6-phosphate dehydrogenase activity. Glycation, the
      non-enzymic reaction between a free amino group in proteins and a reducing sugar,
      slowly inactivates gluthathione-related and other enzymes. In addition,
      glutathione can be also glycated. The presence of glutathione, and of the related
      enzymes has been also reported in other parts of the eye, such as ciliary body
      and trabecular meshwork, suggesting that the same enzyme systems are present in
      all tissues of the eye to generate NADPH and to maintain gluthatione in the
      reduced form. Changes of glutathione and related enzymes activity in lens,
      cornea, retina and other eye tissues, occur with ageing, cataract, diabetes,
      irradiation and administration of some drugs.

PMID- 16421015
TI  - Unique ultrastructure of exorbital lacrimal glands in male NOD and BALB/c mice.
AB  - Lacrimal glands of male NOD and BALB/c mice have very small, pleomorphic acinar
      lumens. Acini contain isolated zones of highly complex cell surface
      interdigitations at the basal surface, sometimes occurring between acinar and
      myoepithelial cells. In NOD mice, cytological abnormalities, including
      mitochondrial deterioration, pleomorphic and heterogeneous cytoplasmic vacuoles,
      and lipid accumulation are evident within acinar cells at 1 month. Accumulation
      of lipid is further increased as the animal ages, accompanied by lymphocytic
      infiltration and destruction of acini. These results demonstrate alterations from
      normal cytology as early as 1 month in NOD mice, well before detection of
      clinical signs of Sjogren syndrome.

PMID- 16421016
TI  - Effectiveness of fluoroquinolones against Mycobacterium abscessus in vivo.
AB  - PURPOSE: To determine the effectiveness of fluoroquinolones against Mycobacterium
      abscessus in vivo. METHODS: M. abscessus growth was determined quantitatively in
      rabbit corneas after intrastromal bacterial injection (10(4) CFU/cornea; n >or= 4
      corneas per group). Eyes were treated topically with 0.3% ciprofloxacin, 0.5%
      levofloxacin, or 0.5% moxifloxacin by three protocols: (1) 1 drop of antibiotic
      applied hourly for 10 hr on day 3 postinfection (PI); (2) 1 drop applied every 2
      hr for 10 hr on days 2 and 3 PI; or (3) 1 drop applied every 2 hr for 10 hr on
      days 1, 2, and 3 PI. Corneas were cultured 1 hr after the last topical drop.
      Results are expressed as the log CFU. RESULTS: Bacteria in control group reached
      maximal numbers in vivo by day 3 PI (approximately 6 logs CFU/cornea). Treatment
      of infected eyes on day 3 with moxifloxacin or levofloxacin resulted in
      approximately 2.0 log decrease in CFU/cornea relative to the untreated control.
      Treatment on days 2 and 3 with moxifloxacin or levofloxacin resulted in
      approximately 3.0 and 2.5 log CFU/cornea decrease, respectively. Ciprofloxacin
      had no effect on bacterial load. Treatment on days 1, 2, and 3 with moxifloxacin
      resulted in a 5.5 log CFU decrease, whereas treatment with levofloxacin or
      ciprofloxacin resulted in a approximately 4.0 log CFU decrease. CONCLUSIONS:
      Moxifloxacin, and to a lesser extent levofloxacin and ciprofloxacin, demonstrated
      significant effectiveness for reducing the number of M. abscessus in vivo,
      suggesting the potential usage of these agents in prevention of M. abscessus
      keratitis.

PMID- 16421017
TI  - Fibrin glue as a suture substitute: histological evaluation of trabeculectomy in
      rabbit eyes.
AB  - PURPOSE: To describe the outcome of the use of fibrin adhesive (Quixil) in
      penetrating trabeculectomy in a rabbit model. METHODS: Fibrin adhesive was used
      experimentally to attach the conjunctiva and the scleral flap in two groups of 17
      New Zealand albino adult rabbits (34 eyes). In the first experiment (20 eyes),
      the fibrin adhesive was used to reattach the tissue after conjunctival peritomy
      and scleral flap only in 14 eyes (experiment I). In 6 eyes (controls), the
      conjunctiva was attached with nylon sutures. In the second experiment (14 eyes),
      the fibrin adhesive was used after conjunctival peritomy, scleral flap, and
      penetrating trabeculectomy in 8 eyes (experiment II). In a control group of 6
      eyes, nylon sutures were used to attach the scleral flap and the conjunctiva
      after penetrating trabeculectomy. Biomicroscopy and histopathological
      examinations were performed on postoperative days 1, 3, 7, 14, 21, and 30.
      Intraocular pressure was measured before and after surgery in the second
      experiment. Main outcome measures are histological presence of adhesive in the
      tissue, degree of capillary congestion, inflammatory reaction, collagen density
      [scar formation] and clinical (IOP measurements before and after surgery,
      conjunctival chemosis, anterior chamber reaction, presence of filtering bleb and
      wound leakage). RESULTS: In experiments I and II, the adhesive was well
      identified histologically in the tissue as an amorphic eosinophilic substance for
      up to day 3 and nearly disappeared by day 7. An acute inflammatory reaction was
      noted for up to 14 days, which converted to chronic inflammation with collagen
      deposits and scar formation by day 30. Similar inflammatory reaction was observed
      in the control group. The adhesive had no adverse effects on ocular tissue
      compared with sutures. One eye in experiment II demonstrated wound dehiscence.
      Intraocular pressure dropped from 17.35 mmHg preoperatively to 8.28 mmHg on
      postoperative day 1 in experiment II, and from 17.2 mmHg to 11.5 mmHg in the
      controls. No significant change in intraocular pressure was noted in experiment
      I. CONCLUSIONS: The fibrin adhesive had no adverse effects on ocular tissue
      compared with sutures. It might serve as an effective substitute for conjunctival
      and scleral wound closure in trabeculectomy surgery.

PMID- 16421019
TI  - Termination of systemic immunity in the presence of intraocular tumors: influence
      of ocular immune privilege on tumor vaccines.
AB  - Ocular immune privilege preserves the visual axis by preventing the induction of
      sight-threatening nonspecific inflammation. Although privilege is essential for
      maintaining visual integrity, intraocular tumors exploit the privileged
      environment and grow progressively within the anterior chamber of the eye.
      Recently, a large number of laboratories have constructed genetically engineered
      tumor cell vaccines that express high levels of costimulatory signals. These
      vaccines are designed to bypass the normal pathways of T-cell activation and
      directly activate CD8+ tumor-specific T cells. In the following series of
      experiments, we determined whether a tumor cell vaccine that uses costimulatory
      signals (CD80 and IL-12) is capable of eliminating tumors within the immune
      privileged anterior chamber. As expected, vaccine-immunized mice rejected
      subcutaneous flank tumors (a non-privileged site). However, the vaccine failed to
      protect mice from even a small number of tumor cells transplanted into the immune
      privileged anterior chamber. Surprisingly, immunized mice that were
      simultaneously challenged with subcutaneous and anterior chamber tumors were
      unable to eliminate tumors at either site. The failure of systemic protective
      immunity coincided with the loss of tumor-specific delayed hypersensitivity and
      cytotoxic T cells. We conclude that tumor cell vaccines that induce complete
      protection against tumors in non-immune-privileged sites fail to protect against
      the same tumor within an ocular immune-privileged site. Moreover, a tumor that
      escapes elimination within the eye can terminate systemic protective immunity
      that is induced by the tumor cell vaccine.

PMID- 16421018
TI  - Pattern-reversal visual evoked potentials in patients with human T-lymphotropic
      virus type 1 uveitis.
AB  - PURPOSE: The purpose of this study was to evaluate the possible injury in the
      optic pathway by measuring P100 peak latency of pattern-reversal visual evoked
      potentials (PVEPs) in patients with human T-lymphotropic virus type 1 uveitis
      (HU). METHODS: The P100 peak latency of PVEP was measured during the period
      without macular abnormalities observed by fluorescein angiography in 23 patients
      (46 eyes) with HU and 24 patients (48 eyes) with Vogt-Koyanagi-Harada disease
      (VKH) with a corrected visual acuity of 20/25 or more. To determine the normal
      upper limit of P100 peak latency, PVEPs were measured in 31 normal subjects (31
      eyes). In addition, in the HU patients, the serum anti-HTLV-1 antibody titer was
      measured by particle agglutination assay within 3 months of PVEP recording, and
      the period of HU was retrospectively surveyed. RESULTS: Delayed latency was
      observed in 4 (7 eyes) of the 23 patients (46 eyes) with HU but none of the 24
      patients (48 eyes) with VKH. All four patients with delayed latency showed a
      serum anti-HTLV-1 antibody titer of more than x4000. The HU period in the HU
      patients was 0.2-14.0 years, and the HU periods in the four patients with delayed
      latency were 0.8, 2.7, 4.2, and 14.0 years, respectively. CONCLUSIONS: We
      measured pattern-reversal visual evoked potentials and observed delayed P100 peak
      latency in 7 of the 46 eyes in 4 (17.4%) of the 23 HU patients. This suggests
      injury in the optic pathway including the optic nerve by HTLV-1 in some patients
      with HU. In the future, consideration should also be given to the possible
      development of optic neuropathy due to HTLV-1.

PMID- 16421020
TI  - KI-67 immunopositivity in choroidal and ciliary body melanoma with respect to
      nucleolar diameter and other prognostic factors.
AB  - PURPOSE: To study the association of cell proliferation in uveal melanoma with
      the mean of the 10 largest nucleoli (MLN), microvascular prognostic factors, and
      survival. METHODS: Population-based, retrospective cohort study of 167 choroidal
      and ciliary body melanomas enucleated from 1972 to 1981. Mouse monoclonal
      antibody Ki-67 (clone 7B11) was used to identify proliferating cells. MLN was
      measured from silver stained slides. Kaplan-Meier and Cox regression analysis
      were performed. RESULTS: The median number of Ki-67 immunopositive cells was 8
      per tumor cross-section (range, 0-272) corresponding to a median of 0.30
      cells/mm2. The percentage of immunopositive cells was 0.02% of all cells (range,
      0-3.2). Tumors with epithelioid cells tended to have a higher percentage of
      immunopositive cells (p = 0.089). Ki-67 immunoreactivity, MLN, and presence of
      extravascular loops and networks were independent predictors of melanoma-related
      mortality, whereas Ki-67 immunoreactivity was not an independent predictor of
      mortality when presence of epithelioid cells was in the model. CONCLUSIONS: Taken
      together with previous data, the results of this population-based study support
      the theory that high cell proliferation index is associated with presence of
      epithelioid cells and that presence of a high cell proliferation index is
      associated with a higher risk of metastatic death independent of MLN,
      microvascular density, and presence extravascular loops and networks.

PMID- 16421021
TI  - Protective effect of donepezil on retinal ganglion cells in vitro and in vivo.
AB  - The neuroprotective effect of donepezil, an acetylcholinesterase inhibitor on
      retinal ganglion cells (RGCs), was examined. The survival of purified RGCs after
      exposure to glutamate with or without donepezil (10(- 7) M to 10(- 5) M) was
      measured after 3 days in culture. In vivo, the neuroprotective effect of
      donepezil was examined by quantifying the number of viable RGCs 7 days after
      axotomy in adult rats. In vitro, donepezil dose-dependently reduced RGC death
      caused by glutamate toxicity. Oral administration of donepezil (10 mg kg(-1) day(
      1)) significantly reduced RGC death after axotomy. In conclusion, donepezil
      exerts a protective effect on RGCs both in vitro and in vivo.

PMID- 16421022
TI  - An endothelin type A receptor antagonist reverses upregulated VEGF and ICAM-1
      levels in streptozotocin-induced diabetic rat retina.
AB  - Diabetic retinopathy, a cause of blindness, is often associated with the
      upregulation of vascular endothelial growth factor (VEGF) in the retina.
      Recently, leukocyte adhesion (leukostasis) is claimed for the occlusion of
      retinal capillary vascularity, which ultimately assists in the progression of
      diabetic retinopathy. In addition, intercellular adhesion molecule-1 (ICAM-1), a
      representative factor for leukostasis, is increased in diabetic retina.
      Endothelin (ET)-1, a potent vasoconstrictor peptide, is closely linked to the
      pathogenesis of diabetic retinopathy. Different therapeutic interventions
      concerning VEGF have already been proposed to prevent diabetic retinopathy.
      However, no study has yet reported concerning the effects of ET-1 receptor
      antagonist on the upregulated VEGF and ICAM-1 in morphologically intact diabetic
      retina. The current study investigated the effect of ET(A) receptor antagonist
      (TA-0201; 1 mg kg(-1) day(-1)) on the expressions of VEGF and ICAM-1 in rat
      diabetic retina. Diabetes was induced by intraperitoneal injection of
      streptozotocin (70 mg/kg) in Sprague-Dawley rats, whereas control rats (Cont)
      received only citrate buffer. After 1 week, the streptozotocin-administered rats
      were randomly divided into two groups: ET(A) receptor antagonist-treated group
      (DM+TA-0201) and saline-treated group (DM+vehicle). After the treatment for 4
      weeks, the retina was removed from the eyeball. In DM+vehicle group, the VEGF
      expression of retina was significantly increased (33.5 pg/mg) in comparison with
      that in the Cont group (25.1 pg/mg), and the upregulation of VEGF was reversed in
      DM+TA-0201 group (26.9 pg/mg), a phenomenon consistent with the change in VEGF
      mRNA levels. The expression of retinal ICAM-1 was increased in DM+vehicle group
      (55.1 pg/mg) compared with Cont group (43.8 pg/mg), and ET antagonism completely
      blocked this increase (43.8 pg/mg). Moreover, an increased leukostasis by 3.3
      fold in DM+vehicle retina was returned to the control level by ET antagonism. In
      the current study, there was no obvious retinal morphological alteration from
      both the hematoxylin and eosin staining and the FITC-dextran angiography. Thus,
      ET(A) receptor antagonist might be useful in preventing the progression of
      diabetic retinopathy, as evidenced by suppressing the increase in VEGF and ICAM-1
      levels as well as leukostasis in morphologically intact diabetic retina.

PMID- 16421023
TI  - Local patterns of image degradation differentially affect refraction and eye
      shape in chick.
AB  - PURPOSE: To evaluate visual blur as a mechanism for modulating eye shape.
      METHODS: Chicks wore a unilateral full goggle or one of several goggles modified
      with apertures. After 2 weeks, eyes were measured with refractometry, ultrasound,
      and calipers, and three retinal regions were assayed for dopamine and DOPAC (3,4
      dihydroxyphenylacetic acid). RESULTS: Goggled eyes were diffusely enlarged or
      enlarged predominantly along the axial dimension, depending on the goggle. Myopia
      developed under goggle types inducing primarily axial growth and under some of
      the goggles inducing diffuse eye expansion. Enlarged eyes remained emmetropic
      beneath other goggles that caused diffuse eye expansion. Reductions in retinal
      dopamine and DOPAC were proportional to the eye growth and refraction effects.
      CONCLUSIONS: Localized image degradation can cause myopia with predominantly
      axial expansion, myopia with more diffuse vitreous chamber expansion, or eye
      expansion without myopia. Robust expansion of the equatorial diameter alone was
      not observed. The associated alterations in retinal dopamine metabolism are
      consistent with a hypothesized role of dopaminergic amacrine cells in the visual
      regulation of eye growth. Besides refraction and overall size, visual blur can
      affect eye shape; but the goggle responses do not correspond to a simple
      summation of blur signals across the retina. Therefore, other mechanisms
      seemingly are needed to account for the full range of refractions and ocular
      shapes seen in chicks and, by analogy, in humans.

PMID- 16421024
TI  - Small eye phenotypes observed in a human tau gene transgenic rat.
AB  - We developed a rat line showing small eye from transgenic rats that were obtained
      by microinjection of a DNA segment containing the human (h)tau cDNA (GenBank:
      BC000558: 31-677,774-1180) expressed under control of CAG promoter, which is
      related to Alzheimer disease, into the pronuclei rat embryos. The rat line was
      established by selective brother-sister mating of rats showing small eyes. Of 11
      offspring in the 11th generation, there were eight animals with microphthalmia
      and the transgene. The remaining three rats without transgene did not show the
      small eyes phenotype. The globes of affected rats were 1.2 mm in length compared
      with normal globes (3.5 mm), and all other ocular structures were normal. The
      expression of hTau protein was evident immunohistochemically in the ciliary body,
      extraocular muscle, lens epithelium, and pigment epithelium. Cytogenetic analysis
      suggested that the chromosome location of the transgene was chromosome 1 (1p12).
      This region may include genes related to lens development, such as Cat5.

PMID- 16421025
TI  - Physical activity and mental health in schoolchildren: a complicated
      relationship.
AB  - According to a study by Parfitt and Eston, physical activity was positively
      associated with child mental health and self-esteem. In this commentary, gender
      differences, causal links and implications for prevention are discussed.
      CONCLUSION: The relationship between physical activity and mental health is not
      as simple as to say that activity will invariably lead to improved mental health.
      For youngsters to be engaged in physical exercise, it is important that the needs
      of the particular child be taken into account. Forced and frightening activities
      should be avoided. The context should be one of enjoyment rather than of harsh
      discipline and skill-dependent games where many children are apt to fail.

PMID- 16421026
TI  - On the clinical relevance of early deficits in critical linguistic functions.
AB  - The clinical significance of patterns of deficits in semantic and phonological
      representations observed by Miniscalco et al. is discussed in light of an
      ecological approach to language development. CONCLUSION: Deficits in semantic
      representations reflect problems in capturing the core linguistic referential
      function and should be taken as serious early warning signals for language delay.

PMID- 16421027
TI  - Maternal anxiety: an emerging prognostic factor in neonatology.
AB  - Symptoms of anxiety in pregnant and postpartum women are of considerable concern
      due to their association with adverse obstetrical outcomes, postpartum
      depression, and emotional and behavioral problems in the children. Certain
      mothers are at particularly high risk for anxiety in the immediate postpartum
      period: those who have experienced preterm birth or other perinatal
      complications, as well as those lacking a satisfactory marital relationship or
      other forms of social support. CONCLUSION: Programs to detect and intervene with
      anxious mothers in the early postpartum period are warranted.

PMID- 16421028
TI  - Pervasive loss of function in asylum-seeking children in Sweden.
AB  - Presently, a couple of hundred children from traumatized asylum-seeking families
      in Sweden have developed severe loss of mental and physical functions without
      evidence of underlying disease. Of the 23 treated children treated at this
      clinic, 15 have recovered, three are improving and five are under initial care.
      Communication within the family is crucial from both pathogenic and salutogenic
      perspectives. A permanent residence permit, correcting the underlying situation
      of threat and insecurity, is a condition for good results from psychiatric
      treatment. In Sweden there is a lack of consensus and conflicting political and
      medical perspectives prevail regarding the "apathetic" children. CONCLUSION:
      Children living under unbearable life conditions can develop life-threatening
      depression-withdrawal stress reactions well known as pervasive refusal syndrome
      (PRS). This is also true of children in traumatized asylum-seeking families.
      Excellent results are achieved when the family's underlying fear and hopelessness
      can be erased and the treatment focuses on the traumatic experiences.

PMID- 16421029
TI  - Proteomic evaluation of milk from different mammalian species as a substitute for
      breast milk.
AB  - As milk represents the main source of nutrition for infants, the question of an
      effective human milk substitute becomes mandatory when a formula-fed baby is
      allergic to cows' milk proteins. In this case, formulas containing extensively
      hydrolysed milk proteins should be preferred, but even such a formula may cause
      allergic reactions in highly sensitive patients. If there is evidence of cows'
      milk allergy with IgE-associated symptoms, after 6 mo of age, a soy bean formula
      may be recommended only when tolerance to soy protein has been established by
      clinical challenge. In infants with allergic reactions to cows' milk proteins,
      even after extensive hydrolyzation, proteomic techniques coupled to immunological
      methods may make it possible to select other milk products that do not contain
      the same allergens as ordinary cow's milk. In this paper, evidence will be
      presented that proteomic evaluation of proteins from different mammalian species
      may be a suitable method of testing whether proteins from the milk of different
      mammalian species may be used as a substitute for untreated bovine milk.
      CONCLUSION: Proteomic evaluation of milk from different mammalian species may not
      only be of help when recommending suitable feeding in cases of cows' milk allergy
      but also gives new insight into the background to allergic reactions caused by
      milk proteins.

PMID- 16421030
TI  - Introduction of complementary food to infants within the first six months
      postpartum in rural Vietnam.
AB  - AIM: To document the introduction of complementary food and factors influencing
      the decision to feed infants with solid food within 6 mo postpartum in rural
      Vietnam. METHODS: A longitudinal study of 463 women who gave birth during August
      October 2002 was conducted. RESULTS: An early introduction of complementary food
      was found, which increased from 16.4% at week 1 to 56.5% at week 16 and nearly
      100% at week 24. Home-cooked solid food was introduced by 4.8%, 40.9% and 74.3%
      of women at weeks 1, 16 and 24, respectively. Logistic regression analysis found
      that at week 24 postpartum, it was less likely for the infant to be fed with
      solid food if the mother was a farmer (OR 0.52, 95% CI: 0.18-0.95) and passed
      secondary school (OR 0.28, 95% CI: 0.10-0.54), whose husband was satisfied with
      the infant's sex (OR 0.30, 95% CI: 0.17-0.53), her mother-in-law preferred
      exclusive breastfeeding (OR 0.18, 95% CI: 0.04-0.75), or her friends practised
      exclusive breastfeeding (OR 0.41, 95% CI: 0.16-1.10). However, infants were
      likely to be fed with solid food when their parents had higher income and lived
      independently (OR 1.76, 95% CI: 1.01-3.06). CONCLUSION: Community mobilization
      for sharing the workload with women could help them to cope with employment and
      breastfeeding.

PMID- 16421031
TI  - Association between prenatal treatment and clinical manifestations of congenital
      toxoplasmosis in infancy: a cohort study in 13 European centres.
AB  - AIM: To determine the effectiveness of prenatal treatment for clinical
      manifestations of congenital toxoplasmosis. METHODS: We prospectively identified
      255 live-born infants with congenital toxoplasmosis using prenatal or neonatal
      screening. We determined the effect of prenatal treatment on the risks of
      intracranial or ocular lesions in infancy, accounting for gestational age at
      maternal seroconversion. RESULTS: Prenatal treatment within 4 wk of
      seroconversion reduced the risk of intracranial lesions compared with no
      treatment (odds ratio, OR 0.28; 95% CI: 0.08-0.75), but there was no significant
      effect when initiated after 4 wk (OR 0.76; 95% CI: 0.35-1.59; overall p-value
      0.19). Compared to spiramycin alone, no treatment doubled the risk of
      intracranial lesions (OR 2.33; 95% CI: 1.04-5.50), but the risk did not differ
      with pyrimethamine-sulphonamide treatment (overall p-value 0.52). There was no
      consistent relationship between the type or timing of treatment and the risk of
      ocular lesions. Gestational age at maternal seroconversion was inversely
      associated with the risk of intracranial but not ocular lesions. CONCLUSION: Only
      early versus no prenatal treatment for intracranial lesions showed a
      statistically significant benefit. A large randomized controlled trial and/or
      meta-analysis of individual patient data from cohort studies is required to
      confirm these findings.

PMID- 16421033
TI  - Efficacy of an individualized written home-management plan in the control of
      moderate persistent asthma: a randomized, controlled trial.
AB  - BACKGROUND: The management of childhood asthma necessitates a comprehensive
      approach including pharmacological treatment as well as education about self
      evaluation and home management of the condition. AIM: To evaluate the efficacy of
      adding an individualized written home-management plan in the control of moderate
      persistent asthma. METHODS: Children with moderate persistent asthma were
      randomized to receive either an individualized written home-management plan or no
      plan, in addition to standard asthma therapy including education. They were
      followed up with serial measurement of outcome variables. RESULTS: Children
      receiving an individualized written home-management plan had fewer acute asthma
      events, fewer lost school days, lower symptom score and less nocturnal awakening
      than those who did not receive a written plan. CONCLUSION: The addition of a
      written individualized home-management plan improves overall control in children
      with moderate persistent asthma.

PMID- 16421032
TI  - Effect of obesity on inflammatory markers and renal functions.
AB  - AIM: To examine the relationship between inflammation criteria and body mass
      index in otherwise-healthy obese schoolchildren and to evaluate the effect of
      obesity on renal functions. METHODS: Sixty-five otherwise-healthy obese children
      (median age 10.8 y, range 7.1-16.5 y; median body mass index 26.8 kg/m(2), range
      19.9-38.7 kg/m(2)) and 20 healthy controls (median age 12.4 y, range 10.1-17.1 y;
      median body mass index 18.8 kg/m(2), range 17.3-23.1 kg/m(2)) were included.
      Blood and urine samples were taken from every child. RESULTS: Children in the
      obese and control groups had similar age and sex distributions (p>0.05).
      Inflammatory mediators were higher in obese children (p<0.05). A significant
      positive correlation was found between glomerular filtration rate and body mass
      index in the whole study group (r=0.39, p=0.001). A positive correlation was
      found between body mass index standard deviation and inflammatory mediators and
      glomerular filtration rate. No significant difference existed regarding protein
      and microalbumin excretion in the urine. CONCLUSION: Inflammatory mediators
      increased significantly in obese children, and the glomerular filtration rate
      increased as the body mass index increased. To prevent obesity-related
      complications in adulthood, it is important to take measures to prevent
      development of obesity during childhood.

PMID- 16421034
TI  - Effect of regular ingestion of Saccharomyces boulardii plus inulin or
      Lactobacillus acidophilus LB in children colonized by Helicobacter pylori.
AB  - AIM: To evaluate the effect of a probiotic, Lactobacillus acidophilus LB (LB), or
      a synbiotic, Saccharomyces boulardii plus inulin (SbI), on Helicobacter pylori
      (Hp) colonization in children. SUBJECTS AND METHODS: A clinical trial was carried
      out in a school from a low socio-economic area of Santiago. Two hundred and fifty
      four asymptomatic children (8.40+/-1.62 y) were screened for Hp by the (13)C-Urea
      Breath Test ((13)C-UBT). Hp-positive children were randomly distributed into
      three groups to receive either antibiotic treatment (lanzoprazole, clarythromycin
      and amoxicillin) for 8 d, or SbI or LB daily for 8 wk. A second (13)C-UBT was
      carried out at this time. Spontaneous clearance was evaluated in the same way in
      81 infected, untreated children. The differences in the delta(13)CO(2) over
      baseline values before and after treatments (?DOB) were evaluated. RESULTS: 182
      subjects (71.7%) were colonized by Hp, and 141 of them completed their treatment
      (22.5% dropout). Hp was eradicated in 66%, 12% and 6.5% of the children from the
      Ab, SbI and LB groups, respectively, while no spontaneous clearance was observed
      in the children without treatment. A moderate but significant difference in ?DOB
      was detected in children receiving living SbI (-6.31; 95% CI: -11.84 to -0.79),
      but not in those receiving LB (+0.70; 95% CI: -5.84 to +7.24). CONCLUSION: S.
      boulardii seems promising as an agent that interferes with Hp in colonized
      individuals. More studies are needed to confirm these results and to elucidate
      the mechanisms by which Sb inhibits Hp.

PMID- 16421035
TI  - Laparoscopic nephrectomy for congenital benign renal diseases in children:
      comparison with adults.
AB  - AIM: To compare the results of laparoscopic nephrectomy for congenital benign
      renal diseases in children and adults. METHODS: From August 1996 to February
      2003, laparoscopic nephrectomies were performed on 26 children and 60 adults. Of
      these patients, 33 patients (17 children, 16 adults) with comparable diseases
      were included in the analysis. RESULTS: Disease was on the right side in 16
      patients and on the left in 17. Operative and convalescence parameters, including
      operative time, blood loss, transfusion rate, conversion rate to open surgery,
      resumption of oral intake, hospital stay, and complication rate, were evaluated
      in both groups. Median operative time in the paediatric group was 140 min
      compared to 147.5 in adults (p=0.626). The estimated blood loss was significantly
      different (median 25 and 75 cm(3) in children and adults, respectively; p<0.001).
      Other operative and convalescence parameters were not statistically different.
      However, whereas no child required a blood transfusion, three adults (18.8%) did.
      No major perioperative complications occurred in the paediatric group, but open
      surgical exploration was needed due to retroperitoneal bleeding in a single
      adult. CONCLUSION: Our findings indicate that laparoscopic nephrectomy for
      congenital benign disease in children is achieved safely and that the modality
      offers additional advantages in children as compared to adults.

PMID- 16421036
TI  - Topographic localization of electrocortical activation in newborn and two- to
      four-month-old infants in response to head-up tilting.
AB  - AIMS: (1) To confirm that head-up tilting causes sustained increases in the heart
      rate (HR) of newborn infants but not during the period of maximum vulnerability
      to SIDS at 2-4 mo of age, and (2) to determine whether electrocortical activation
      (changes in high-frequency EEG power) also shows topographic and age-dependent
      effects of tilting. METHODS: HR and electrocortical activity were recorded in 15
      newborn and 12 2- to 4-mo-old infants during head-up tilting. Infants were
      tilted, three times, to a 30 degrees head-up position. Electrocortical activity
      was acquired using a 128-lead EEG system. Changes in HR and high-frequency (12-50
      Hz) power in the electrocortical signal were computed from the flat to the head
      up position. RESULTS: Newborn infants had significant increases in HR and robust
      increases in high-frequency power in the left frontal, right frontal-temporal,
      and occipital regions following head-up tilt. At 2 to 4 mo of age, HR did not
      change significantly and tilt-related increases in high-frequency power were
      smaller. CONCLUSION: The patterns of HR change and electrocortical activation
      with tilting of newborn infants are different from infants at the age of highest
      risk for SIDS.

PMID- 16421037
TI  - Effects of tidal volume and positive end-expiratory pressure during resuscitation
      of very premature lambs.
AB  - BACKGROUND: Guidelines recommend neonatal resuscitation without controlling tidal
      volume or positive end-expiratory pressure (PEEP). However, these may improve gas
      exchange, lung volume and outcome. AIM: To investigate resuscitation of very
      premature lambs with a Laerdal bag without PEEP versus volume guarantee
      ventilation with PEEP. METHODS: Anaesthetized lambs (n=20) delivered at 125 d
      gestation were randomized to three groups receiving 15 min resuscitation: (1)
      Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm
      H(2)O PEEP; (3) ventilation with 10 ml/kg and 8 cm H(2)O PEEP. They were then all
      ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H(2)O PEEP.
      Ventilation parameters and blood gases were recorded. RESULTS: Different tidal
      volumes affected PaCO(2) within minutes, with 10 ml/kg causing severe hypocarbia.
      PEEP had little effect on PaCO(2). Oxygenation improved significantly with PEEP
      of 8 cm H(2)O, irrespective of tidal volume. CONCLUSION: Very premature lambs can
      be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal
      volumes affected PaCO(2) within minutes but had little effect on oxygenation.
      PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature
      babies with controlled tidal volumes and PEEP might improve their outcome.

PMID- 16421038
TI  - Pre-discharge anxiety among mothers of well newborns: prevalence and correlates.
AB  - OBJECTIVE: To explore the prevalence and correlates of maternal postpartum
      anxiety. METHODS: 422 of 973 invited mothers (43%) were screened for anxiety
      before hospital discharge with the State-Trait Anxiety Inventory (STAI). Recent
      medical and social life events, stress, resiliency (mastery, social support, and
      marital satisfaction), length of stay, discharge readiness, anticipatory medical
      care, and history of psychiatric illness and depression were assessed by
      questionnaire and medical record review. RESULTS: 24.9% of mothers had moderate
      and 1% severe anxiety. Higher anxiety was observed among young, unmarried,
      primiparous mothers with male infants, and anxiety correlated with medical and
      negative social life events, stress, history of depression, and duration of
      postpartum stay. Inverse correlations were observed with maternal education and
      household income, pregnancy planning, prenatal class attendance, infant
      healthcare provider identification, and with all resiliency factors. In
      multivariate models, pre-discharge anxiety was significantly associated with
      medical life events and the maternal perception of perinatal stress, and
      negatively associated with mastery, marital satisfaction, and choice of infant
      healthcare provider. CONCLUSION: Moderate maternal anxiety is common prior to
      perinatal hospital discharge, especially among women with low mastery and marital
      satisfaction, stressful perinatal courses, and failure to identify an infant
      healthcare provider.

PMID- 16421039
TI  - A framework for ethical decision making in neonatal intensive care.
AB  - Intensive care for neonates with high risks of severe impairment and the
      possibility of a prolonged dying process represents a frequent ethical issue in
      neonatal units. The aim of this paper is to present a framework for structured
      decision making that has been developed in a neonatal intensive care unit and to
      demonstrate its impact on the healthcare team and on survival of critically ill
      neonates. This framework attempts to integrate the best interests of the infants
      and their parents, the possibilities of high-tech neonatal intensive care
      interventions, and the perspective of the nurses and doctors. An external
      evaluation of 84 sessions over 3 y revealed a beneficial effect on the quality of
      the decision-making process itself and on the quality of the teamwork in the
      unit. Survival time was shorter (median 2 d, interquartile range 1-7 d) in 26
      infants that died after structured decision making compared with 26 controls
      matched for gestational age, malformation and intracranial haemorrhage (median 7
      d, interquartile range 4-15 d). CONCLUSION: The introduction of this framework
      for structured decision making involving doctors and nurses improved the quality
      of the teamwork. It shortened futile intensive care, and thereby suffering for
      both infants and parents.

PMID- 16421040
TI  - Prescribers' indications for drugs in childhood: a survey of five European
      countries (Spain, France, Bulgaria, Slovakia and Russia).
AB  - BACKGROUND: Indication-based, in comparison to diagnoses-based, drug utilization
      studies in children are scarce in the literature. AIM: To determine the adequacy
      of the prescriber's indications for specific drug treatments compared to the
      current literature in five different European countries; and to show the
      possibilities of performing indication-based drug utilization studies. DESIGN: a
      descriptive, cross-sectional, international study. PATIENTS AND METHODS: Randomly
      selected sample of 12,264 paediatric outpatients seen in consultation rooms
      attended by paediatricians or general practitioners. Data on patient
      demographics, diagnoses, and pharmacological treatment, with therapeutic
      indications for each drug, were collected in pre-designed forms. Diagnoses and
      indications were coded using the ICD-9 and drugs according to the ATC
      classifications. RESULTS: Indications were registered for every drug prescribed
      in all locations. Antibiotic indications considered incorrect (common cold, upper
      respiratory tract infections, viral infections, general symptoms or "not
      specified") accounted from 24.1% of the total antibiotics prescribed in Tenerife
      to 67.4% in Slovakia. Incorrect indication of first-choice antibiotics prescribed
      in acute otitis media and tonsillitis ranged from 28.9% of total antibiotics use
      in Russia to 75.4% in Tenerife. Correct antibiotic indications ranged from 23.4%
      of total antibiotics used in Slovakia to 65.7% in Tenerife. Aspirin use in
      febrile viral conditions was detected mainly in Toulouse and Russia. CONCLUSION:
      The main areas for improvement detected were high use of mucolytics, prescription
      of aspirin in potential or established viral infections, overuse of antibiotics
      and identification of specific patterns of incorrect antibiotic prescription and
      clinical entities associated with each location.

PMID- 16421041
TI  - The relationship between children's habitual activity level and psychological
      well-being.
AB  - AIM: To explore the relationship between habitual physical activity and
      psychological well-being in children. METHODS: Seventy children (35 boys, 35
      girls), age 10.4+/-0.4 y, wore hip pedometers over a period of 7 d. Well-being
      was conceptualized as the presence of global self-esteem and the absence of
      anxiety and depression and assessed with the use of three questionnaires.
      RESULTS: Correlation analyses revealed that habitual physical activity had a
      strong association with global self-esteem (r=0.66), depression (r=-0.60) and
      anxiety (r=-0.48). However, using partial correlations, the significant
      relationships were removed for anxiety and depression, but remained for self
      esteem (r=0.36). When groups were created based upon activity level, children
      achieving >12,000 steps/day had more positive psychological profiles than
      children achieving <9,200 steps/day. CONCLUSION: The results support the findings
      from previous studies that have explored the relationship between physical
      activity and well-being, but represent the first to use a mechanical measure of
      physical activity over a 7-d period to assess the relationships. The actual step
      counts associated with more positive psychological well-being can be shown to be
      in line with the recommended guidelines that children accumulate a minimum of 60
      min of moderate-intensity activity per day.

PMID- 16421042
TI  - Language skills at age 6 years in Swedish children screened for language delay at
      2(1/2) years of age.
AB  - This study concerns language outcome in 6-y-old children who participated in a
      longitudinal community-based study of 105 children screened for language delay
      (LD) at 2(1/2) y of age. The purpose was to investigate (1) whether results from
      the 2(1/2)-y screening were persistent at 6 y of age, and (2) what language
      domains at age 6 were difficult for (a) children with LD at age 2(1/2) y and (b)
      children with normal language (LN) at the same age. Significant differences
      between LD and LN at age 2(1/2) y were persistent at age 6. The vulnerability
      that was identified at 2(1/2) y of age, such as problems with going from single
      word utterances to multi-word utterances, seems to persist as delayed development
      at different language levels and across language domains. CONCLUSION: This study
      has shown that children who failed the 2(1/2)-y screening are at high risk of
      having persistent language problems at age 6 y.

PMID- 16421043
TI  - Being old-for-grade and drug use: not such a clear connection.
AB  - AIM: To assess whether repeating a grade was associated with drug use among
      adolescents after controlling for personal, family and school-related variables,
      and whether there were differences between students in mandatory and post
      mandatory school. METHODS: Data were drawn from the Catalonia Adolescent Health
      Survey, a cross-sectional study of in-school adolescents aged 14-19 y. The index
      group included 366 subjects who were repeating a grade at the time the survey was
      carried out (old-for-grade, OFG). A control group matched by gender, school and
      being one grade ahead was randomly chosen among all the subjects who had never
      repeated a grade. All statistically significant variables in the bivariate
      analysis were included in a multivariate analysis. In a second step, all analyses
      were repeated for students in mandatory (14-16 y) and post-mandatory (17-19 y)
      school. RESULTS: After controlling for background variables, subjects in the
      index group were more likely to perceive that most of their peers were using
      synthetic drugs and to have ever used them, to have bad grades and a worse
      relationship with their teachers. OFG students in mandatory school were more
      likely to have divorced parents, bad grades and have ever used synthetic drugs,
      whereas they were less likely to be regular drinkers. OFG students in post
      mandatory school were more likely to have below average grades, to be regular
      smokers and to perceive that most of their peers used synthetic drugs.
      CONCLUSIONS: When background variables are taken into consideration, the
      relationship between repeating a grade and drug use is not so clear. By
      increasing the familial and academic support of adolescents with academic
      underachievement, we could reduce their drug consumption.

PMID- 16421044
TI  - Ultrasound diagnosis of brain atrophy is related to neurodevelopmental outcome in
      preterm infants.
AB  - BACKGROUND: Intraventricular haemorrhage and periventricular leukomalacia are
      associated with poor outcome of very preterm infants, while the role of more
      subtle cerebral alterations, as detected by cranial ultrasound, is less clear.
      AIM: In this study, we related periventricular echodensities and signs of brain
      atrophy to neurodevelopmental outcome at 3 y of age. PATIENTS AND METHODS: All
      preterm infants born in 1997 in our institution with a gestational age <32 wk or
      birthweight <1500 g were subjected to repeated standardized cranial ultrasound
      examinations until discharge. Survivors were examined at 3 y of age employing the
      Bayley Scales of Infant Development II. RESULTS: Eighty-seven infants were
      enrolled (birthweight 430-2500 g (median 1200 g), gestational age 24-34 wk
      (median 29 wk)). Periventricular echodensities were detected in 42 infants (48%);
      in 12 cases persisting <7 d, in 30 cases >7 d. At discharge, 18 infants (22%) had
      signs of brain atrophy. Neurodevelopmental outcome was assessed in 64 infants.
      Infants with signs of brain atrophy scored significantly lower on MDI (atrophy
      91.8, no atrophy 101.9; p=0.02), PDI (atrophy 91.4, no atrophy 106.5; p=0.001)
      and Behaviour Rating Scale (atrophy 41.1, no atrophy 66.4; p=0.01) than infants
      without atrophy. Periventricular echodensities were not related to outcome.
      CONCLUSION: Our data show that infants with sonographic signs of brain atrophy at
      discharge achieve lower scores in neurodevelopmental testing at 3 y.

PMID- 16421046
TI  - Use of polyvinyl feeding tubes and iatrogenic pharyngo-oesophageal perforation in
      very-low-birthweight infants.
AB  - BACKGROUND: Placement of a feeding tube may be associated with various
      complications, including iatrogenic pharyngo-oesophageal perforation. AIM: To
      determine the incidence of pharyngo-oesophageal perforation secondary to the use
      of polyvinyl feeding tubes in newborns weighing less than 1500 g, we conducted a
      retrospective study over a 3(1/2)-y period. METHODS: All the hospital files of
      the 371 very-low-birthweight newborns admitted were retrospectively reviewed.
      RESULTS: Three iatrogenic pharyngo-oesophageal perforations were observed, giving
      an incidence of 1:124 preterm infants. This incidence reaches values of 1:25
      newborns weighing less than 750 g. Data from our cases included clinical
      presentation and outcome, radiological evaluation, and type of feeding tube. One
      infant died of sepsis, and the clinical course was compatible with mediastinitis.
      The other two infants were treated successfully with conservative non-surgical
      management. CONCLUSION: Pharyngo-oesophageal perforation in our experience
      exclusively involved preterm infants weighing less than 750 g after traumatic
      placement of a polyvinyl feeding tube. The use of a silastic feeding tube with a
      really soft end instead of polyvinyl catheters could probably avoid iatrogenic
      oesophageal perforation.

PMID- 16421045
TI  - Vitamin K status of preterm infants with a prolonged prothrombin time.
AB  - AIM: To investigate the vitamin K status of preterm infants who have a prolonged
      prothrombin time (PT) in the first month of life. METHODS: Measures of vitamin K
      status were assessed in 21 preterm infants who were found to have an abnormal PT,
      despite 0.2-0.5 mg vitamin K(1) prophylaxis at birth. RESULTS: All infants had
      normal or supraphysiological vitamin K(1) concentrations and undetectable or, in
      one infant, insignificant PIVKA-II, indicating adequate vitamin K status.
      CONCLUSION: In preterm infants born at <32 wk gestation who received > or = 0.2
      mg vitamin K(1) after delivery, a prolonged PT in the first month of life is
      unlikely to be due to vitamin K deficiency.

PMID- 16421047
TI  - Interleukin-13 is involved in the survival of children with sepsis.
AB  - Forty-eight children with sepsis were studied. Interleukin-13 (IL-13) levels were
      lower in patients who died at admission (p=0.014) and at 6 h (p=0.037), and in
      patients with refractory shock at 0 (p=0.03) and particularly at 6 h (p=0.0009).
      IL-13 levels did not correlate with other cytokines (IL-1b, IL-10, IL-12, TNFr),
      CRP or neutrophil count. Low IL-13 levels in the early hours of sepsis are
      associated with poor prognosis. CONCLUSION: IL-13, a Th-2 cytokine fundamental in
      the pathogenesis of atopy, might also have a protective role against severe
      infections in children.

PMID- 16421048
TI  - Adolescent detainees in an adult prison in Geneva.
AB  - Despite the Convention on the Rights of the Child, some adolescents are still
      detained in adult prisons in Europe. Little is known about their health status.
      This cross-sectional study of 67 teenagers detained in an adult prison in
      Switzerland shows that morbidity in this group is high. CONCLUSION: These results
      highlight the need for developmentally appropriate health services for teenagers
      in adult prisons. The long-term implications of detention of adolescents in adult
      detention facilities also need to be discussed.

PMID- 16421049
TI  - Nils Rosen von Rosenstein and neonatal jaundice in the 18th century.
AB  - BACKGROUND: Nils Rosen von Rosenstein (1706-1773) was a Swedish nobleman and a
      professor at Uppsala University. His series of lectures on children's diseases
      and their treatment was published in 1764 under the title Underrattelser om Barn
      Sjukdomar och Deras Bote-Medel. MATERIALS AND METHODS: Rosen von Rosenstein's
      book was translated into several languages. The present paper deals with the
      opinions and advice proffered on the jaundiced neonate in chapter 25 of the
      Danish edition from 1769. RESULTS: The distinction between jaundice in the
      neonate and jaundice in older children is not clear everywhere in the chapter,
      and much of Rosen von Rosenstein's advice on therapy appears to be intended for
      all age groups. Rosen von Rosenstein believed that neonatal jaundice was less
      common in Sweden than elsewhere, and ascribed this to the common practice of
      purging newborns with a manna sugar laxative. The principal cause of jaundice,
      according to Rosen von Rosenstein, was bile stasis. When milk curdled in the
      stomach, the curds could plug the common bile duct, and bile would be forced into
      the lymphatics and from there into the blood. Thus, the bile was carried around
      the body and caused the skin and the sclera, as well as other organs, to become
      yellow. Cure was usually easy-a laxative in the form of pureed manna with
      powdered rhubarb was what Rosen von Rosenstein recommended. CONCLUSION: Rosen von
      Rosenstein's opinions and advice concerning neonatal jaundice were not original,
      and did not differ from those found in other medical texts from the 18th and 19th
      centuries. The bile stasis explanation for all kinds of jaundice, including
      neonatal jaundice, was widely held in the 18th century, and continued to
      predominate in paediatric texts until the end of the 19th century. Similarly,
      laxatives and enemas as the cure-all for many ailments held sway until the late
      1800s.

PMID- 16421050
TI  - Hyperglycaemia and insulinopenia in a neonate with cystic fibrosis.
AB  - Abnormal glucose tolerance is a frequent late complication of cystic fibrosis
      (CF), but the prevalence of CF-related diabetes mellitus (CFRD) in children less
      than 10 y old is less than 2%. The youngest child with CFRD reported to date was
      6 mo of age. Insulinopenia is the primary cause of abnormal glucose
      tolerance/CFRD, but it is unknown whether it may begin in the neonatal period. We
      describe a case of a neonate with CF who presented with hyperglycaemia in the
      diabetic range and marked insulinopenia. Insulinopenia and impaired glucose
      tolerance were permanent findings at 6 and 15 mo of age. CONCLUSION: This case
      suggests that abnormal glucose tolerance/diabetes may occur much earlier in the
      course of CF, even during neonatal age. Careful follow-up and further studies in
      CF infants could reveal that the real incidence of glucose intolerance and
      diabetes in this age group has been underestimated.

PMID- 16421051
TI  - Congenital chylothorax associated with isolated congenital hypoplastic superior
      caval vein: a case report.
AB  - Congenital absence, or hypoplasia, of the superior vena cava (SVC) with situs
      solitus is quite uncommon. Most cases have been found incidentally and
      concomitant with left persistent SVC or other cardiac disorders. Congenital
      chylothorax may be associated with cardiac anomalies, various syndromes, thoracic
      ductal or venous thrombosis, birth trauma or local compression of the thoracic
      duct, but it is rarely caused directly by congenital SVC anomalies. CONCLUSION:
      We report a rare case of congenital chylothorax associated with isolated
      congenital hypoplastic SVC and underdeveloped collateral circulation.

PMID- 16421052
TI  - Fetal hydrops in GM(1) gangliosidosis: a case report.
AB  - GM(1) gangliosidosis is a rare disorder characterized by deficiency of the ss
      galactosidase enzyme, with the resulting accumulation of glycolipids,
      oligosaccharides and especially GM(1) ganglioside. It can be classified into
      three clinical types according to the time of onset: infantile, juvenile and
      adult form. We report a case of GM(1) gangliosidosis presenting with fetal
      hydrops at 24 wk of gestation. The parents were consanguineous; the baby, born at
      35 wk of gestation, was dysmorphic and presented severe generalized oedema. The
      most common cause of fetal hydrops was excluded. A lysosomal storage disease was
      suspected, and GM(1) gangliosidosis was diagnosed. The child developed severe
      growth and mental retardation and died when she was 21 mo old. CONCLUSION: We
      suggest that the possible association between inborn errors of metabolism and
      antenatal ascites should be considered, in order to offer genetic counselling due
      to the high recurrence risk and the availability of early antenatal diagnosis.

PMID- 16421053
TI  - Cirrhosis in an infant heterozygous for classical citrullinaemia.
AB  - Classical citrullinaemia is caused by the inherited deficiency of
      argininosuccinate synthetase. Although varying degrees of liver involvement have
      been observed in urea cycle defects, including classical citrullinaemia, the co
      existence of liver failure in a patient heterozygous for the disease has not been
      reported before. A female infant was investigated to find out the aetiology of
      early infantile liver failure. She was later found to be a heterozygote for the
      G390R mutation found in severe citrullinaemia patients. CONCLUSION: Classical
      citrullinaemia is a phenotypically heterogeneous disease, and observations for
      signs of its presence should be made even in heterozygotes.

PMID- 16421054
TI  - A case of macroprolactinoma and elevated insulin-like growth factor-I in a young
      boy.
AB  - We report a case of a 10-y-old boy who presented with persistent headache and was
      found to have a giant prolactinoma. Laboratory evaluation revealed markedly
      elevated prolactin (PRL) level, thyroid-stimulating hormone (TSH) deficiency, and
      elevated insulin-like growth factor-I (IGF-I). He had normal random growth
      hormone (GH) but non-suppressible GH during oral glucose tolerance test (OGTT).
      Cabergoline treatment was initiated and was well tolerated. Therapy successfully
      reduced PRL levels, normalized IGF-I levels, and reduced tumor size. CONCLUSION:
      Our patient presented with a GH-PRL-secreting tumor. Dopamine agonists are
      recommended as the treatment of choice for prolactinomas. However, there should
      be careful attention to GH status when treating GH-PRL-secreting tumor with
      dopamine agonists alone. IGF-I levels should be followed in all patients with
      prolactinoma, even in those with normal basal GH concentrations, because of the
      possibility of GH co-secretion.

PMID- 16421055
TI  - Faecal calprotectin in children with chronic gastrointestinal symptoms.
AB  - AIMS: Faecal calprotectin, a neutrophil cytosolic protein, is raised in
      inflammatory bowel disease. We assessed this investigation in evaluating children
      with chronic intestinal symptoms. METHODS: Stool samples from 100 children aged 5
      17 years (referrals to the regional paediatric gastroenterology service) were
      tested using a commercially available kit. RESULTS: Calprotectin was higher in
      inflammatory bowel disease than normal children (p<0.0001) or in those with
      functional constipation (p<0.0001). The overall specificity for organic bowel
      disorders was 85%. Calprotectin correlated with C-reactive protein in
      inflammatory bowel disease (p=0.001), and clinical disease activity in ulcerative
      colitis (p=0.017), but not with disease activity in Crohn's disease. CONCLUSION:
      Raised faecal calprotectin should prompt further assessment in children with
      chronic intestinal symptoms, since an organic bowel disorder is likely. However,
      calprotectin cannot be regarded as a specific test for idiopathic inflammatory
      bowel disease.

PMID- 16421056
TI  - Raynaud phenomena and migraine in two children: inclusion within a family of
      related disorders.
AB  - We report a case of two siblings with Raynaud phenomena and migraine, whose
      symptoms were successfully treated with pizotifen. CONCLUSION: To our knowledge,
      this is the first case documenting the association between Raynaud phenomena and
      migraine in two siblings with a family history of Raynaud phenomena and ischaemic
      heart disease.

PMID- 16421057
TI  - Transverse myelitis due to echovirus type 30.

PMID- 16421060
TI  - Mild traumatic brain injury and anxiety sequelae: a review of the literature.
AB  - There is scattered but significant psychological and neuropsychological evidence
      to suggest that mild traumatic brain injury (mild TBI) plays a notable role in
      the emergence and expression of anxiety. Conversely, there is also empirical
      evidence to indicate that anxiety may exert a pronounced impact on the prognosis
      and course of recovery of an individual who has sustained a mild TBI. Although
      the relationship between mild TBI and anxiety remains unclear, the present body
      of research attempts to elucidate a number of aspects regarding this topic.
      Overall, the mild TBI research is rife with inconsistencies concerning prevalence
      rates, the magnitude and implications of this issue and, in the case of PTSD,
      even whether certain diagnoses can exist at all. This review obviates the need
      for greater consistencies across studies, especially between varying disciplines,
      and calls for a shift from studies overly focused on categorical classification
      to those concerned with dimensional conceptualization.

PMID- 16421061
TI  - Aquatics, health-promoting self-care behaviours and adults with brain injuries.
AB  - PRIMARY OBJECTIVE: To determine the effect of an aquatic programme on the health
      promoting behaviours of adults with brain injuries. MAIN OUTCOMES AND RESULTS:
      Eighteen individuals participated in the programme and were randomly assigned to
      an experimental (n = 9) or control group (n = 9). Health promoting behaviours,
      physical self-concept and self-esteem were measured pre- and post-intervention.
      Significant differences and large effect sizes were found between scores for the
      experimental group only, indicating an increase in health promoting behaviours,
      physical self-concept and self-esteem. CONCLUSIONS: Results have useful
      implications for health professionals as exercise prescription may enhance health
      promoting behaviours and decrease health care costs after a brain injury.

PMID- 16421062
TI  - Exploring eye movement analysis as a measure of selective visual attention in
      brain injured individuals.
AB  - PRIMARY OBJECTIVE: To investigate the utility of using a new method of assessment
      for deficits in selective visual attention (SVA). METHODS AND PROCEDURES: An
      independent groups design compared six participants with brain injuries with six
      participants from a non-brain injured control group. The Sensomotoric Instruments
      Eye Movement system with remote eye-tracking device (eye camera) and two sets of
      eight stimuli were employed to determine if the camera would be a sensitive
      discriminator of SVA in these groups. MAIN OUTCOMES AND RESULTS: The attention
      profile displayed by the brain injured group showed that they were slower, made
      more errors, were less accurate and more indecisive than the control group.
      CONCLUSIONS: The utility of eye movement analysis as an assessment method was
      established, with implications for rehabilitation requiring further development.

PMID- 16421063
TI  - A study investigating the effects of Tai Chi Chuan: individuals with traumatic
      brain injury compared to controls.
AB  - OBJECTIVE: To explore the effects of a 6-week course in Tai Chi associated with
      traumatic brain injury (TBI) symptoms. METHOD: Eighteen participants, with TBI
      assigned to a control (waiting list) group (n = 9) or Tai Chi group (n = 9)
      completed the Medical Outcome Scale Short Form 36 (SF-36) and Rosenberg Self
      Esteem Scale (RSES) before, during, immediately after and 3 weeks after
      completion of the Tai Chi course. The Tai Chi group completed the Visual Analogue
      Mood Scales (VAMS) before and after each class. RESULTS: Tai Chi was associated
      with significant improvement on all VAMS scores (except fatigue) with decreases
      in sadness, confusion, anger, tension, fear and increases in energy and
      happiness. There were no significant between-group differences on the SF-36 or
      RSES. CONCLUSIONS: Tai Chi provides short-term benefits after TBI, with rigorous
      outcome measurement needed to examine long-term benefits.

PMID- 16421064
TI  - Reduced daytime activity in patients with acquired brain damage and apathy: a
      study with ambulatory actigraphy.
AB  - PRIMARY OBJECTIVE: Apathy is difficult to assess in clinical practice. Ambulatory
      actigraphy was used with the aim to measure locomotor activity during the daytime
      as a correlate of self-initiated action in brain-damaged patients with apathy.
      RESEARCH DESIGN: Twenty-four patients with acquired brain damage and high levels
      of apathy or low levels of apathy as well as 12 healthy controls were
      investigated using a parallel group design. METHODS AND PROCEDURES: Apathy was
      diagnosed after clinical observation and evaluated with the apathy evaluation
      scale. Locomotor activity was measured with a wrist-worn actigraph over 3 days.
      RESULTS: High apathy patients showed significantly reduced locomotor activity and
      more episodes of inactivity (naps) during the daytime. Self-rated apathy
      correlated with daytime activity, nap frequency and cognitive (executive)
      deficits. CONCLUSIONS: Ambulatory actigraphy is a promising method to evaluate
      self-initiated action in patients with apathy.

PMID- 16421065
TI  - Neurocognitive fitness in the sub-acute stage after mild TBI: the effect of age.
AB  - OBJECTIVE: Age is assumed to be a negative prognostic factor in recovery from
      moderate-to-severe traumatic brain injury (TBI). Little is known on cognitive
      performance after mild TBI in relation to age in the sub-acute stage after
      injury. METHOD: Ninety-nine mild TBI subjects (age 15-75) were compared with 91
      healthy control subjects (age 14-74) in a case-control design. Patients were
      matched on age, sex and level of education, with control subjects. Mean interval
      between injury and cognitive assessment was 13 days. Neurocognitive test battery
      contained tests of verbal memory, selective attention, general speed of
      information processing and verbal fluency. RESULTS: An overall effect was found
      of a single mild TBI on neurocognitive performance in the sub-acute stage after
      injury. Age did not add significantly to the effect of mild TBI on cognitive
      functioning. CONCLUSION: Patients suffering from mild TBI are characterized by
      subtle neurocognitive deficits in the weeks directly following the trauma. The
      notion that elderly subjects have a worse outcome in the sub-acute period after
      mild TBI is at least not in line with the results of this study.

PMID- 16421066
TI  - Evaluation of a coping skills group following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To examine the impact of a cognitive behaviour therapy (CBT)
      based intervention programme, termed the Coping Skills Group (CSG), on coping
      strategy use and emotional adjustment. RESEARCH DESIGN: Thirty-one individuals
      with TBI participated and a wait-list control design was used. METHODS AND
      PROCEDURES: The CSG ran twice a week, for 5 weeks and focused on developing
      adaptive coping skills for the management of emotional and adjustment issues.
      MAIN OUTCOMES AND RESULTS: Following the CSG, the majority of participants
      subjectively reported that they had a better understanding of emotional issues
      and an improved ability to implement strategies to manage these issues. Adaptive
      coping, as measured on the Coping Scale for Adults, increased significantly
      immediately following intervention. However, no significant changes in anxiety,
      depression, self-esteem and psychosocial function were observed on the measures
      used. CONCLUSIONS: The results suggest that it may be possible to modify coping
      strategy use following brain injury, through CBT.

PMID- 16421067
TI  - Is there a relationship between whiplash-associated disorders and concussion in
      hockey? A preliminary study.
AB  - PRIMARY OBJECTIVE: To examine the relationship between the occurrence of whiplash
      associated disorders and concussion symptoms in hockey players. RESEARCH DESIGN:
      Prospective cohort observational study to examine the relationship between
      whiplash associated disorders and concussion in actual hockey play. METHODS AND
      PROCEDURES: Twenty hockey teams were followed prospectively for one season. Team
      therapists completed acute and 7-10 day follow-up evaluation questionnaires for
      all of the players who received either a whiplash mechanism or a concussion. MAIN
      OUTCOMES AND RESULTS: 183 players were registered for this study; 13 received
      either a whiplash mechanistic injury or a concussion injury. Initial injuries
      ranged from WAD I to WAD III and all subjects reported concussion symptoms. Only
      three subjects reported full resolution of both WAD and concussion symptoms at
      the 7-10 day follow-up evaluation. CONCLUSIONS: There is a strong association
      between whiplash induced neck injuries and the symptoms of concussion in hockey
      injuries. Both should be evaluated when dealing with athletes/patients suffering
      from either injury.

PMID- 16421068
TI  - Human spatial navigation deficits after traumatic brain injury shown in the arena
      maze, a virtual Morris water maze.
AB  - OBJECTIVE: Survivors of traumatic brain injury (TBI) often have spatial
      navigation deficits. This study examined such deficits and conducted a detailed
      analysis of navigational behaviour in a virtual environment. DESIGN: TBI
      survivors were tested in a computer simulation of the Morris water maze task that
      required them to find and remember the location of an invisible platform that was
      always in the same location. A follow-up questionnaire assessed everyday spatial
      ability. METHOD: Fourteen survivors of moderate-to-severe TBI were compared to 12
      non-injured participants. RESULTS: TBI survivors navigated to a visible platform
      but could not learn the location of the invisible platform. The difference
      between TBI survivors and uninjured participants was best indicated by two new
      dependent variables, path efficacy and spatial scores. CONCLUSION: This study
      confirms the capacity of virtual environments to reveal spatial navigation
      deficits after TBI and establishes the best way to identify such deficits.

PMID- 16421069
TI  - Prediction of functional rehabilitation outcomes in clients with stroke.
AB  - OBJECTIVES: To evaluate the validity of the Neurobehavioral Cognitive Status
      Examination (NCSE or Cognistat) and to determine its effects in order to estimate
      the functional outcomes of survivors with stroke. METHODS: The present study
      first studied the factor structure NCSE in 148 Chinese survivors with stroke
      (aged 45-91 years). They were admitted to hospital consecutively and recruited
      prospectively. The relationship of NCSE with Functional Independence Measures
      (FIM), a set of measures commonly adopted as an indicator of the outcome of
      rehabilitation, was studied. RESULTS: One hundred and forty-eight patients with
      stroke (49.3% male, 50.7% female), with a mean age of 70.38 and an average number
      of years of education of 3.50 years joined the study. A two-factor NCSE structure
      was obtained, namely verbal-spatial and integrated cognition, accounting for
      62.77% of the variance. A significant relationship between NCSE factors and the
      functional status of clients with stroke on admission and upon discharge, as well
      as age, years of education and length of hospital stay were indicated.
      CONCLUSIONS: This study supports a systematic relationship between cognitive
      factors and functional outcome in Chinese patients with stroke. Similarities and
      differences in the NCSE factor structure between the population with stroke and
      general neurological populations were discussed and the utility of NCSE in stroke
      rehabilitation, such as its predictive validity in functional independence is
      suggested.

PMID- 16421070
TI  - Post-anoxic myoclonus: a case presentation and review of management in the
      rehabilitation setting.
AB  - Post-anoxic myoclonus is a rare movement disorder manifested by diffuse action
      triggered jerking movements that may result in significant disability. The
      incidence of this disorder is not clearly established, but over 122 cases have so
      far been reported in the literature. The pathogenesis is not entirely known,
      although it has been hypothesized that particular susceptibility of the Purkinje
      cells of cerebellum to anoxic injury may play a key role. A case is presented of
      an independently living 60-year-old woman admitted to the rehabilitation unit
      with diffuse myoclonus after sustaining a cardio-pulmonary arrest. She presented
      with severe jerking movements in all extremities with startle to noise and
      exacerbations upon attempting any purposeful actions. The patient's myoclonus was
      controlled by a variety of anti-epileptic medications. The patient initially
      responded to a combination of divalproex sodium and zonisamide, but relapsed in
      several weeks, requiring addition of levetriacetam and clonazepam. At a 1-year
      follow-up she demonstrated a significant improvement in ambulation and self-care
      activities. This case illustrates that, although patients with post-anoxic
      myoclonus cannot be fully cured, their quality of life can be significantly
      improved by rehabilitation interventions.

PMID- 16421071
TI  - Characteristics of assistive technology service delivery models: stakeholder
      perspectives and preferences.
AB  - PURPOSE: The purpose of this study was to identify the key characteristics of an
      assistive technology service delivery model preferred by the various stakeholders
      in Manitoba, Canada. METHODS: A descriptive, exploratory approach consistent with
      qualitative research design was used to explore this issue. Three focus groups
      were held using a semi-structured interview guide and a hypothetical case study
      to guide the discussion. Eighteen adults participated in the study, each
      representing one of three groups of stakeholders (assistive technology service
      providers, funders and users). Interviews were audiotaped, transcribed and
      analysed using an inductive process to develop categories and themes. RESULTS:
      Three primary themes emerged from the data: the user of assistive technology is a
      unique individual; a decision-making process exists; and, assistive technology
      devices and services are complex. Based on the study results, recommendations for
      the delivery of assistive technology services are outlined. CONCLUSIONS: The
      results of this study may be useful for developing funding guidelines, supporting
      the importance of assistive technology in enabling meaningful activities, and
      examining current delivery of services in different contexts.

PMID- 16421072
TI  - The M3S-based electric wheelchair for the people with disabilities in Taiwan.
AB  - PURPOSE: This study aims to establish an electronic wheelchair system in Taiwan
      that conforms to multiple master-multiple slave (M3S) standards. The proposed
      system could enhance the safety and convenience of people with disabilities.
      MATERIAL AND METHOD: The M3S-based head-controlled electric wheelchair consists
      of three parts: (A) the input device, (B) the output device, and (C) the safety
      device. Head movement can be used as the input control to cause the tilting
      device to produce a corresponding level of analog voltage (backward &
      forward/left & right) which is then transmitted to the analogy/digital conversion
      module to control the output device (wheelchair's motor). Ten subjects with C5
      incompleted spinal cord injury were recruited in the clinical assessment. They
      were randomly assigned into groups A and B. In the group A, the subjects were
      assigned to operate the head-controlled wheelchair system with M3S standard
      before operating the head-controlled wheelchair system without M3S standard. In
      the group B, the subjects were assigned to operate the head-controlled wheelchair
      system without M3S standard before operating the head-controlled wheelchair
      system with M3S standard. Two subjects in the group B drop off due to their
      personal reasons. RESULTS: The time cost for group A in completing tasks 1, 2,
      and 3 with the M3S and without the M3S were insignificant (p>0.05). The time cost
      for completing in group B was insignificant (p>0.05). Thus, the wheelchair
      operating time is depended on the proficiency of the subjects, not the M3S
      standard added. DISCUSSIONS AND CONCLUSIONS: The time cost for subjects to
      operate the wheelchair was determined by their proficiency, not the M3S standard
      control added to the system. However, the M3S-based system did realize the safety
      mechanism and complex auxiliary tools with and without the plug-in and play
      function.

PMID- 16421073
TI  - Reliability of the seated postural control measure for adult wheelchair users.
AB  - PURPOSE: To evaluate the test-retest and interrater reliability of the Seated
      Postural Control Measure for Adults 1.0 (SPCMA 1.0). METHOD: The participants
      were evaluated first by two raters and then, 3 weeks later, by one rater. Section
      1 (one item, seven-point scale) evaluates the adult's overall ability to control
      its posture in a sitting position. Sections 2 and 3 (22 items each, scored on a
      seven-point scale), evaluate the adult's postural alignment in a static position
      and the changes in postural alignment induced by a dynamic activity. RESULTS: For
      the test-retest reliability, the intraclass correlation coefficient (ICC) of
      section 1 was excellent (0.95) and moderate to good for sections 2 and 3 (0.60 -
      0.62) and their subsections (0.47 - 0.78). For interrater reliability, the three
      sections had good to excellent ICCs (0.68 - 0.93) and their subsections had
      moderate to good ICCs (0.41 - 0.69). A large range was observed in Kappa
      coefficients (test-retest and interrater reliability) for the item analysis of
      the sections 2 and 3, due to a lack of variability in some items. CONCLUSIONS:
      The results confirm that the SPCMA is reliable as a whole. Suitable information
      has been obtained for the development of the SPCMA 2.0 and, although further
      psychometric testing is needed, the latter should improve clinical evaluation of
      seated postural control in adult wheelchair users.

PMID- 16421074
TI  - Theory development and a science of rehabilitation.
AB  - PURPOSE: This article considers the role of theory and theory building in science
      and specifically in rehabilitation. It is argued that rehabilitation has tended
      to value theory testing over theory building and some evidence is presented for
      this. METHOD: Some general questions concerning the role of theory in scientific
      progress are discussed including: What is a theory? What is the role of theory in
      science? What makes a good scientific theory? How does theoretical change occur
      in science? Where relevant these questions are discussed in terms of examples
      from clinical rehabilitation research. RESULTS: Two important issues arising from
      the preceding discussion are then considered. First is the question of whether a
      general or unifying theory of rehabilitation is a desirable goal. The second
      concerns how we might begin to develop a coherent programme of theory building in
      rehabilitation. CONCLUSION: More time spent on rehabilitation theory building may
      enhance the fruits of empirical theory testing.

PMID- 16421075
TI  - Theory for all and rehabilitation for the few (with money): who does our theory
      serve?

PMID- 16421076
TI  - Response to: Theory development and a science of rehabilitation (Siegert RJ,
      McPherson KM, Dean SG).

PMID- 16421077
TI  - Response to: Theory development and a science of rehabilitation (Siegert RJ,
      McPherson KM, Dean SG).

PMID- 16421078
TI  - Response to: Theory development and a science of rehabilitation (Siegert RJ,
      McPherson KM, Dean SG).

PMID- 16421079
TI  - Unifying rehabilitation through theory development.

PMID- 16421082
TI  - Effects of formulation factors on encapsulation efficiency and release behaviour
      in vitro of huperzine A-PLGA microspheres.
AB  - To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic
      therapy of Alzheimer's disease, the microsphere was prepared by using an o/w
      emulsion solvent extraction evaporation method based on a series of formulation
      design of the emulsion. The dialysis method was used for release analysis. The
      encapsulation efficiency and release amount of the microspheres were determined
      by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by
      scanning electron microscopy. The distribution of the drug within microspheres
      was observed by a confocal laser scanning microscope. The results indicated that
      the PLGA 15,000 microspheres possessed a smooth and round appearance with average
      particle size of 50 microm or so. The encapsulation percentages of microspheres
      prepared from PLGA 15,000, 20,000 and 30,000 were 62.75%, 27.52% and 16.63%,
      respectively. The drug release percentage during the first day decreased from
      22.52% of PLGA 30,000 microspheres to 3.97% of PLGA 15,000 microspheres, the
      complete release could be prolonged to 3 weeks. The initial burst release of
      microspheres with higher molecular weight PLGA could be explained by the
      inhomogeneous distribution of drug within microspheres. The encapsulation
      efficiency of the microspheres improved as the polymer concentration increased in
      the oil phase and PVA concentration decreased in the aqueous phase. The burst
      release could be controlled by reducing the polymer concentration. Evaporation
      temperature had a large effect on the drug release profiles. It had better be
      controlled under 30 degrees C. Within a certain range of particle size,
      encapsulation efficiency decreased and drug release rate increased with the
      reducing of the particle size.

PMID- 16421083
TI  - Microencapsulation of higher hydrocarbon phase change materials by in situ
      polymerization.
AB  - Three higher hydrocarbon phase change materials (PCMs) with melting points of 25,
      40 and 50 degrees C were microencapsulated by in situ polymerization of amino
      aldehyde resins. Trimethylolmelamine (TMM) and hexamethoxymethylolmelamine (HMMM)
      were studied as amino-aldehyde pre-polymers for microcapsule wall formation, in
      combination with emulsifying/modifying agents based on styrene-malein anhydride
      copolymers (SMA) of different molecular weights and different styrene-maleic acid
      anhydride ratios. Microcapsule sizes, size distribution and wall permeability
      were analysed. A mathematical model was developed for comparing the mechanical
      resistance of different batches of microcapsules, produced at different TMM-SMA
      ratios. Larger microcapsules with thicker walls and larger pores (M(LAR))
      expressed lower resistance to breakage than slightly smaller microcapsules with
      thinner walls and finer pore structure (M(SMA)). Mathematical data were confirmed
      by a smudging colouration test. Laboratory microencapsulation process parameters
      were optimized to obtain impermeable microcapsules with improved mechanical
      stability. The process was transferred into a 10l pilot reactor for two PCMs with
      melting points of 25 and 40 degrees C. Dry powder of microencapsulated PCMs was
      obtained by spray drying of aqueous microcapsule suspensions.

PMID- 16421084
TI  - Mucosal delivery of cytotoxic therapeutic agents: response of rat nasal mucosa to
      microencapsulated ethopropazine HCl enantiomer.
AB  - Use of microencapsulation technology in combination with absorption enhancers
      eliminated epithelium irritation and necrosis commonly associated with nasal
      delivery of cytotoxic therapeutic agents. Phenothiazines, such as ethopropazine
      (ETZ), promethazine, trimeprazine and propiomazine have been used for the
      treatment of allergenic conditions, motion sickness, nausea, Parkinson's disease,
      Prion disease and as a sedative for psychiatric disorders. The enantiomers of
      commercially available racemic phenothiazines were isolated and purified using
      classical diastereomeric salt techniques. The racemate and the enantiomers of ETZ
      were tested in vitro for their cellular toxicity using lung fibroblast cells.
      Each enantiomer was shown to be cytotoxic at concentrations greater than 10(-5)
      molar. The ETZ enantiomers were encapsulated using spinning disk atomization to
      prepare a nasal delivery dosage form that does not produce an irritation
      response. Release rates for the ETZ microcapsules were determined in vitro and an
      animal study was conducted to determine the irritation response of rat nasal
      mucosa when dosed with encapsulated vs. non-encapsulated ETZ.

PMID- 16421085
TI  - Monodisperse structured multi-vesicle microencapsulation using flow-focusing and
      controlled disturbance.
AB  - A method to produce monodisperse structured microcapsules in the diameter range
      from 10-100 microm is here presented. Flow-focusing is a well known technique
      whereby a steady capillary micro-jet is generated by the action of a highly
      accelerated co-flowing stream forced through a small orifice. The micro-jet
      breaks up owing to capillary instability, giving rise to droplets with a narrow
      size distribution. In the present study, flow-focusing gives rise not to simple
      but to compound capillary jets. At break-up, under suitable control parameters,
      such jets give rise to microcapsules where an outer liquid (shell liquid)
      surrounds a core liquid integrated by one or more vesicles. Furthermore, under
      adequate stimulation combining a sinusoidal signal with intermittent pulses, the
      jet break-up can be controlled. Highly monodisperse microcapsules are produced;
      fundamental geometric parameters (main diameter, shell thickness or number of
      cores) are reliably controlled. Rather than using a gas flow to focus the
      concentric stream of two immiscible liquids, this study has investigated in some
      detail the evolution of a concentric stream of three immiscible liquids forced
      through a small orifice. The selection of the surface tension coefficients
      between the three phases ensures the robust production of a microcapsule
      structure involving a plurality of vesicles homogeneously distributed in the
      capsule bulk, the number of cores being a freely chosen parameter. Such composite
      microcapsules find a broad field of technological applications in the
      pharmaceutical, food or biotechnology industries.

PMID- 16421086
TI  - Effects of divalent cations on drug encapsulation efficiency of deacylated gellan
      gum.
AB  - The objective of this research was to evaluate the effects of various divalent
      cations on the encapsulation efficiency of gellan gum and to probe the underlying
      mechanisms responsible for drug-loading efficiency. Spherical beads containing
      azathioprine were prepared from deacetylated gellan gum by ionotropic gelation
      method. One molar solution of various divalent chlorides (MgCl(2), BaCl(2),
      CaCl(2), CuCl(2) and ZnCl(2)) and two additional concentrations of CaCl(2) (2.5 M
      and 5.0 M) were used as ionotropic media. Drug solubility was also determined in
      these ionotropic media and statistically evaluated using ANOVA. Solubility in
      various divalent chloride solutions (1.0 M) suggests that azathioprine forms
      complex with Ca(2+), Zn(2+) and Cu(2+), while there might be a formation of
      poorly water-soluble chelates with Mg(2+) and Ba(2+) as solubility in these media
      were less than in deionized water. The encapsulation efficiency of gellan gum was
      much higher in the presence of transition elements (Cu(2+) and Zn(2+)) when
      compared to alkaline earth metal ions (Ca(2+), Mg(2+) and Ba(2+)). Higher
      concentrations of Ca(2+) decreased the encapsulation efficiency of gellan gum in
      a nearly proportional manner. The correlation between encapsulation efficiency
      and pH of the ionotropic media was negative and significant (r=-0.9574, p<0.05),
      although the solubility of azathioprine seems to be independent of the pH of the
      ionotropic medium. Overall, the results suggest that drug encapsulation
      efficiency of deacetylated gellan gum is largely affected by the concentration
      and nature of various divalent cations (e.g. atomic number, valency or electro
      positivity, co-ordination property, etc.) and pH of the ionotropic medium.

PMID- 16421087
TI  - Production of haloperidol-loaded PLGA nanoparticles for extended controlled drug
      release of haloperidol.
AB  - This study developed an emulsion-solvent evaporation method for producing
      haloperidol-loaded PLGA nanoparticles with up to 2% (wt/wt. of polymer) drug
      content, in vitro release duration of over 13 days and less than 20% burst
      release. The free haloperidol is removed from the nanoparticle suspension using a
      novel solid phase extraction technique. This leads to a more accurate
      determination of drug incorporation efficiency than the typical washing methods.
      It was discovered that PLGA end groups have a strong influence on haloperidol
      incorporation efficiency and its release from PLGA nanoparticles. The hydroxyl
      terminated PLGA (uncapped) nanoparticles have a drug incorporation efficiency of
      more than 30% as compared to only 10% with methyl-terminated PLGA (capped)
      nanoparticles. The in vitro release profile of nanoparticles with uncapped PLGA
      has a longer release period and a lower initial burst as compared to capped PLGA.
      By varying other processing and materials parameters, the size, haloperidol
      incorporation and haloperidol release of the haloperidol-loaded PLGA
      nanoparticles were controlled.

PMID- 16421088
TI  - Viability analysis of alginate encapsulated micro-organisms using fluorescent
      stains.
AB  - The encapsulation of micro-organisms such as bacteria and fungi in biopolymers is
      currently being evaluated as delivery systems in many fields. Information about
      the viability and morphology of the organisms in the microparticle is often
      required to ascertain the longevity of the systems. A rapid method using
      fluorescent stains for microbial viability has been validated for organisms
      within alginate microparticles. Usually viability is assessed by dissolving the
      microparticles and cell culturing. This new method is advantageous for slow
      growing or filamentous organisms because these are not quickly or accurately
      enumerated by plate counts. In addition, the technique also allows the morphology
      of the organism to be monitored over time.

PMID- 16421091
TI  - Literature alerts.

PMID- 16421089
TI  - PEG-derivative effectively modifies the characteristics of indomethacin-PLGA
      microspheres destined to intra-articular administration.
AB  - The aim of this study was to obtain biodegradable indomethacin microspheres for
      intra-articular administration in rheumatoid arthritis, where angiogenic
      processes are involved. Indomethacin concentrations to achieve an anti-angiogenic
      effect would be five-times higher than an anti-inflammatory. Microspheres were
      prepared by solvent evaporation using PLGA. Indomethacin is a poor water-soluble
      drug with it being possible that dissolved and non-dissolved drug co-exist within
      the polymeric matrix resulting in rapid release. To control this release, an oil
      PEG-derivative was incorporated, producing changes in morphology, crystallinity
      and indomethacin release. To minimize the amount of microspheres administered, a
      two-factor five-level central rotable composite 2(2)+star design was employed
      with two independent variables: indomethacin percentage and PEG-derivative
      percentage. The optimum formulation showed mean encapsulation efficiency of
      94.3+/-2.2% and released 7.99+/-0.25 microg indomethacin/day/mg microspheres for
      21 days. A dose of 20-50 mg of this formulation could be appropriate to achieve
      both anti-angiogenic and anti-inflammatory effects. Preliminary cytotoxicity
      studies performed in rat splenocytes showed an adequate cell viability.

PMID- 16421093
TI  - Replisome architecture and dynamics in Escherichia coli.

PMID- 16421094
TI  - SUMO-1 controls the protein stability and the biological function of phosducin.
AB  - Phosducin regulates Gbetagamma-stimulated signaling by binding to Gbetagamma
      subunits of heterotrimeric G-proteins. Control of phosducin activity by
      phosphorylation is well established. However, little is known about other
      mechanisms that may control phosducin activity. Here we report that phosducin is
      regulated at the posttranslational level by modification with the small ubiquitin
      related modifier, SUMO. We demonstrate modification with SUMO for phosducin in
      vitro expressed in cells and for native phosducin purified from retina and the
      heart. A consensus motif for SUMOylation was identified in phosducin at amino
      acid positions 32-35. Mutation of the conserved lysine 33 to arginine in this
      motif abolished SUMOylation of phosducin, indicating that SUMO is attached to
      lysine 33 of phosducin. In transfected cells the steady-state levels of the K33R
      mutant protein were much lower compared with wild-type phosducin. The
      investigation of the stability of wild-type phosducin and of phosducinK33R showed
      a decreased protein stability of the SUMOylation-deficient mutant. The decreased
      protein stability correlated with increased ubiquitinylation of the SUMOylation
      deficient mutant. These findings indicate that SUMOylation protects phosducin
      from proteasomal degradation. SUMOylation of phosducin decreased its ability to
      bind Gbetagamma. PhlP, a closely related member of the phosducin family, was not
      a target for SUMOylation, but its SUMOylation can be achieved by a single amino
      acid insertion in the conserved N terminus of PhlP. Together, these findings show
      that phosducin is a previously unrecognized target of SUMO modification and that
      SUMOylation controls phosducin stability in cells as well as its functional
      properties.

PMID- 16421095
TI  - Structural and functional characterization of PseC, an aminotransferase involved
      in the biosynthesis of pseudaminic acid, an essential flagellar modification in
      Helicobacter pylori.
AB  - Helicobacter pylori flagellin is heavily glycosylated with the novel sialic acid
      like nonulosonate, pseudaminic acid (Pse). The glycosylation process is essential
      for assembly of functional flagellar filaments and consequent bacterial motility.
      Because motility is a key virulence factor for this and other important
      pathogens, the Pse biosynthetic pathway offers potential for novel therapeutic
      targets. From recent NMR analyses, we determined that the conversion of UDP-alpha
      D-Glc-NAc to the central intermediate in the pathway, UDP-4-amino-4,6-dideoxy
      beta-L-AltNAc, proceeds by formation of UDP-2-acetamido-2,6-dideoxy-beta-L
      arabino-4-hexulose by the dehydratase/epimerase PseB (HP0840) followed with amino
      transfer by the aminotransferase, PseC (HP0366). The central role of PseC in the
      H. pylori Pse biosynthetic pathway prompted us to determine crystal structures of
      the native protein, its complexes with pyridoxal phosphate alone and in
      combination with the UDP-4-amino-4,6-dideoxy-beta-L-AltNAc product, the latter
      being converted to the external aldimine form in the active site of the enzyme.
      In the binding site, the AltNAc sugar ring adopts a 4C1 chair conformation, which
      is different from the predominant 1C4 form found in solution. The enzyme forms a
      homodimer where each monomer contributes to the active site, and these structures
      have permitted the identification of key residues involved in stabilization, and
      possibly catalysis, of the beta-L-arabino intermediate during the amino transfer
      reaction. The essential role of Lys183 in the catalytic event was confirmed by
      site-directed mutagenesis. This work presents for the first time a nucleotide
      sugar aminotransferase co-crystallized with its natural ligand, and, in
      conjunction with the recent functional characterization of this enzyme, these
      results will assist in elucidating the aminotransferase reaction mechanism within
      the Pse biosynthetic pathway.

PMID- 16421096
TI  - Humanized beta-thalassemia mouse model containing the common IVSI-110 splicing
      mutation.
AB  - Splicing mutations are common causes of beta-thalassemia. Some splicing mutations
      permit normal splicing as well as aberrant splicing, which can give a reduced
      level of normal beta-globin synthesis causing mild disease (thalassemia
      intermedia). For other mutations, normal splicing is reduced to low levels, and
      patients are transfusion-dependent when homozygous for the disease. The
      development of therapies for beta-thalassemia will require suitable mouse models
      for preclinical studies. In this study, we report the generation of a humanized
      mouse model carrying the common IVSI-110 splicing mutation on a BAC including the
      human beta-globin ((hu)beta-globin) locus. We examined heterozygous murine beta
      globin knock-out mice ((mu)beta(th-3/+)) carrying either the IVSI-110 or the
      normal (hu)beta-globin locus. Our results show a 90% decrease in (hu)beta-globin
      chain synthesis in the IVSI-110 mouse model compared with the mouse model
      carrying the normal (hu)beta-globin locus. This notable difference is attributed
      to aberrant splicing. The humanized IVSI-110 mouse model accurately recapitulates
      the splicing defect found in comparable beta-thalassemia patients. This mouse
      model is available as a platform for testing strategies for the restoration of
      normal splicing.

PMID- 16421097
TI  - Alternate recruitment of signal recognition particle and trigger factor to the
      signal sequence of a growing nascent polypeptide.
AB  - Different from cytoplasmic membrane proteins, presecretory proteins of bacteria
      usually do not require the signal recognition particle for targeting to the Sec
      translocon. Nevertheless signal sequences of presecretory proteins have been
      found in close proximity to signal recognition particle immediately after they
      have emerged from the ribosome. We show here that at the ribosome, the molecular
      environment of a signal sequence depends on the nature of downstream sequence
      elements that can cause an alternate recruitment of signal recognition particle
      and the ribosome-associated chaperone Trigger factor to a growing nascent chain.
      While signal recognition particle and Trigger factor might remain bound to the
      same ribosome, both ligands are clearly able to displace each other from a
      nascent chain. The data also imply that a signal sequence owes its molecular
      environment to the fact that it remains closely apposed to the ribosomal exit
      site during growth of a nascent secretory protein.

PMID- 16421098
TI  - The essential vertebrate ABCE1 protein interacts with eukaryotic initiation
      factors.
AB  - The ABCE1 gene is a member of the ATP-binding cassette (ABC) multigene family and
      is composed of two nucleotide binding domains and an N-terminal Fe-S binding
      domain. The ABCE1 gene encodes a protein originally identified for its inhibition
      of ribonuclease L, a nuclease induced by interferon in mammalian cells. The
      protein is also required for the assembly of the HIV and SIV gag polypeptides.
      However, ABCE1 is one of the most highly conserved proteins and is found in one
      or two copies in all characterized eukaryotes and archaea. Yeast ABCE1/RLI1 is
      essential to cell division and interacts with translation initiation factors in
      the assembly of the pre-initiation complex. We show here that the human ABCE1
      protein is essential for in vitro and in vivo translation of mRNA and that it
      binds to eIF2alpha and eIF5. Inhibition of the Xenopus ABCE1 arrests growth at
      the gastrula stage of development, consistent with a block in translation. The
      human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid
      identity allows the evolution of its introns to be examined throughout
      eukaryotes. The demonstration that ABCE1 plays a role in vertebrate translation
      initiation extends the known functions of this highly conserved protein.
      Translation is a highly regulated process important to development and
      pathologies such as cancer, making ABCE1 a potential target for therapeutics. The
      evolutionary analysis supports a model in which an ancestral eukaryote had large
      number of introns and that many of these introns were lost in non-vertebrate
      lineages.

PMID- 16421099
TI  - A synthetic peptidoglycan fragment as a competitive inhibitor of the melanization
      cascade.
AB  - Melanin synthesis is essential for defense and development but must be tightly
      controlled because systemic hyperactivation of the prophenoloxidase and excessive
      melanin synthesis are deleterious to the hosts. The melanization cascade of the
      arthropods can be activated by bacterial lysine-peptidoglycan (PGN),
      diaminopimelic acid (DAP)-PGN, or fungal beta-1,3-glucan. The molecular mechanism
      of how DAP- or Lys-PGN induces melanin synthesis and which molecules are involved
      in distinguishing these PGNs are not known. The identification of PGN derivatives
      that can work as inhibitors of the melanization cascade and the characterization
      of PGN recognition molecules will provide important information to clarify how
      the melanization is regulated and controlled. Here, we report that a novel
      synthetic Lys-PGN fragment ((GlcNAc-MurNAc-L-Ala-D-isoGln-L-Lys-D-Ala)2, T-4P2)
      functions as a competitive inhibitor of the natural PGN-induced melanization
      reaction. By using a T-4P2-coupled column, we purified the Tenebrio molitor PGN
      recognition protein (Tm-PGRP) without causing activation of the prophenoloxidase.
      The purified Tm-PGRP recognized both Lys- and DAP-PGN. In vitro reconstitution
      experiments showed that Tm-PGRP functions as a common recognition molecule of Lys
      and DAP-PGN-dependent melanization cascades.

PMID- 16421101
TI  - Regulation of the monomer-dimer equilibrium in inducible nitric-oxide synthase by
      nitric oxide.
AB  - The oxygenase domain of inducible nitric-oxide synthase exists as a functional
      tight homodimer in the presence of the substrate L-arginine and the cofactor
      tetrahydrobiopterin (H4B). In the absence of H4B, the enzyme is a mixture of
      monomer and loose dimer. We show that exposure of H4B-free enzyme to NO induces
      dissociation of the loose dimer into monomers in a reaction that follows single
      exponential decay kinetics with a lifetime of approximately 300 min. It is
      followed by a faster autoreduction reaction of the heme iron with a lifetime of
      approximately 30 min and the concurrent breakage of the proximal iron-thiolate
      bond, forming a five-coordinate NO-bound ferrous species. Mass spectrometry
      revealed that the NO-induced monomerization is associated with intramolecular
      disulfide bond formation between Cys104 and Cys109, located in the zinc-binding
      motif. The regulatory effect of NO as a dimer inhibitor is discussed in the
      context of the structure/function relationships of this enzyme.

PMID- 16421100
TI  - Accelerated lipid absorption in mice overexpressing intestinal SR-BI.
AB  - Dietary cholesterol absorption contributes to a large part of the circulating
      cholesterol. However, the mechanism of sterol intestinal uptake is not clearly
      elucidated. Scavenger receptor class B type I (SR-BI), major component in the
      control of cholesterol homeostasis, is expressed in the intestine, but its role
      in this organ remains unclear. We have generated transgenic mice overexpressing
      SR-BI primarily in the intestine by using the mouse SR-BI gene under the control
      of intestinal specific "apoC-III enhancer coupled with apoA-IV promoter." We
      found SR-BI overexpression with respect to the natural protein along the
      intestine and at the top of the villosities. After a meal containing
      [(14)C]cholesterol and [(3)H]triolein, SR-BI transgenic mice presented a rise in
      intestinal absorption of both lipids that was not due to a defect in chylomicron
      clearance nor to a change in the bile flow or the bile acid content.
      Nevertheless, SR-BI transgenic mice showed a decrease of total cholesterol but an
      increase of triglyceride content in plasma without any change in the high density
      lipoprotein apoA-I level. Thus, we described for the first time a functional role
      in vivo for SR-BI in cholesterol but also in triglyceride intestinal absorption.

PMID- 16421102
TI  - The growth and tumor suppressor NORE1A is a cytoskeletal protein that suppresses
      growth by inhibition of the ERK pathway.
AB  - NORE1A is a growth and tumor suppressor that is inactivated in a variety of
      cancers. NORE1A has been shown to bind to the active Ras oncogene product.
      However, the mechanism of NORE1A-induced growth arrest and tumor suppression
      remains unknown. Using anchorage-independent growth assays, we mapped the NORE1A
      effector domain (the minimal region of the protein responsible for its growth
      suppressive effects) to the fragment containing the central and Ras association
      domains of NORE1A (amino acids 191-363). Expression of the NORE1A effector domain
      in A549 lung adenocarcinoma cells resulted in the selective inhibition of signal
      transduction through the ERK pathway. The full-length NORE1A (416 amino acids)
      and its fragments capable of growth suppression were localized to centrosomes and
      microtubules in normal and transformed human cells in a Ras-independent manner. A
      mutant that was deficient in binding to centrosomes and microtubules was also
      deficient in inducing cell cycle arrest. This suggests that cytoskeletal
      localization is required for growth-suppressive effects of NORE1A. Ras binding
      function was required for growth-suppressive effects of the full-length NORE1A
      but not for the growth-suppressive effects of the effector domain. Our studies
      suggest that association of NORE1A with cytoskeletal elements is essential for
      NORE1A-induced growth suppression and that the ERK pathway is a target for NORE1A
      growth-suppressive activities.

PMID- 16421103
TI  - Mechanisms of cystic fibrosis transmembrane conductance regulator activation by S
      nitrosoglutathione.
AB  - We investigated the mechanisms by which S-nitrosoglutathione (GSNO) alters cystic
      fibrosis transmembrane conductance regulator (CFTR) mediated chloride (Cl(-))
      secretion across Calu-3 cells, an extensively used model of human airway gland
      serous cells. Confluent monolayers of Calu-3 cells, grown under an air-liquid
      interface, were mounted in Ussing chambers for the measurements of chloride short
      circuit current (I(sc)) and trans-epithelial resistance (R(t)). Addition of GSNO
      into the apical compartment of these chambers resulted in significant and
      sustained increase of I(sc) with an IC(50) of 3.2 +/- 1 mum (mean +/- 1 S.E.; n =
      6). Addition of either glibenclamide or pre-treatment of Calu-3 cells with the
      soluble guanylate cyclase inhibitor 1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one
      totally prevented the GSNO-induced increase of I(sc). Conversely, BAY 41-2272, a
      sGC stimulator, increased I(sc) in a dose-response fashion. The GSNO increase of
      I(sc) was reversed by addition of two phosphatases (PP2A1, PP2A2) into the apical
      compartment of Ussing chambers containing Calu-3 monolayers. Oxy-myoglobin (oxy
      Mb, 300 mum) added into the apical compartment of Ussing chambers either prior or
      after GSNO either completely prevented or immediately reversed the increase of
      I(sc). However, smaller concentrations of oxy-Mb (1-10 mum), sufficient to
      scavenge NO in the medium (as assessed by direct measurement of NO in the Ussing
      chamber using an ISO-NO meter) decreased I(sc) partially. Oxy-Mb did not reverse
      the increase of I(sc) following addition of GSNO and cysteine (50 mum). These
      findings indicate that GSNO stimulates Cl secretion via both cGMP-dependent and
      cGMP-independent mechanisms.

PMID- 16421104
TI  - Influence of membrane composition on osmosensing by the betaine carrier BetP from
      Corynebacterium glutamicum.
AB  - The glycine betaine carrier BetP from Corynebacterium glutamicum was recently
      shown to function as both an osmosensor and osmoregulator in proteoliposomes made
      from Escherichia coli phospholipids by sensing changes in the internal K+
      concentration as a measure of hyperosmotic stress (Rubenhagen, R., Morbach, S.,
      and Kramer, R. (2001) EMBO J. 20, 5412-5420). Furthermore, evidence was provided
      that a stretch of 25 amino acids of the C-terminal domain of BetP is critically
      involved in K+ sensing. This K+-sensitive region has been further characterized.
      Glu572 turned out to be important for osmosensing in E. coli cells and in
      proteoliposomes made from E. coli phospholipids. BetP mutants E572K, E572P, and
      E572A/H573A/R574A were unable to detect an increase in the internal K+
      concentration in this membrane environment. However, these BetP variants regained
      their ability to detect osmotic stress in membranes with increased
      phosphatidylglycerol content, i.e. in intact C. glutamicum cells or in
      proteoliposomes mimicking the composition of the C. glutamicum membrane. Mutants
      E572P and Y550P were still insensitive to osmotic stress also in this membrane
      background. These results led to the following conclusions. (i) The K+ sensor in
      mutants E572Q, E572D, and E572K is only partially impaired. (ii) Restoration of
      activity regulation is not possible if the correct conformation or orientation of
      the C-terminal domain is compromised by a proline residue at position 572 or 550.
      (iii) Phosphatidylglycerol in the membrane of C. glutamicum seems to stabilize
      the inactive conformation of BetP C252T and other mutants.

PMID- 16421105
TI  - A chondroitin sulfate chain attached to the bone dentin matrix protein 1 NH2
      terminal fragment.
AB  - Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein shown by gene
      ablations to be critical for the proper mineralization of bone and dentin. In the
      extracellular matrix of these tissues DMP1 is present as fragments representing
      the NH2-terminal (37 kDa) and COOH-terminal (57 kDa) portions of the cDNA-deduced
      amino acid sequence. During our separation of bone noncollagenous proteins, we
      observed a high molecular weight, DMP1-related component (designated DMP1-PG). We
      purified DMP1-PG with a monoclonal anti-DMP1 antibody affinity column. Amino acid
      analysis and Edman degradation of tryptic peptides proved that the core protein
      for DMP1-PG is the 37-kDa fragment of DMP1. Chondroitinase treatments
      demonstrated that the slower migration rate of DMP1-PG is due to the presence of
      glycosaminoglycan. Quantitative disaccharide analysis indicated that the
      glycosaminoglycan is made predominantly of chondroitin 4-sulfate. Further
      analysis on tryptic peptides led us to conclude that a single glycosaminoglycan
      chain is linked to the core protein via Ser74, located in the Ser74-Gly75
      dipeptide, an amino acid sequence specific for the attachment of
      glycosaminoglycans. Our findings show that in addition to its existence as a
      phosphoprotein, the NH2-terminal fragment from DMP1 occurs as a proteoglycan.
      Amino acid sequence alignment analysis showed that the Ser74-Gly75 dipeptide and
      its flanking regions are highly conserved among a wide range of species from
      caiman to the Homo sapiens, indicating that this glycosaminoglycan attachment
      domain has survived an extremely long period of evolution pressure, suggesting
      that the glycosaminoglycan may be critical for the basic biological functions of
      DMP1.

PMID- 16421107
TI  - Effects of coumarate 3-hydroxylase down-regulation on lignin structure.
AB  - Down-regulation of the gene encoding 4-coumarate 3-hydroxylase (C3H) in alfalfa
      massively but predictably increased the proportion of p-hydroxyphenyl (P) units
      relative to the normally dominant guaiacyl (G) and syringyl (S) units. Stem
      levels of up to approximately 65% P (from wild-type levels of approximately 1%)
      resulting from down-regulation of C3H were measured by traditional degradative
      analyses as well as two-dimensional 13C-1H correlative NMR methods. Such levels
      put these transgenics well beyond the P:G:S compositional bounds of normal
      plants; p-hydroxyphenyl levels are reported to reach a maximum of 30% in
      gymnosperm severe compression wood zones but are limited to a few percent in
      dicots. NMR also revealed structural differences in the interunit linkage
      distribution that characterizes a lignin polymer. Lower levels of key beta-aryl
      ether units were relatively augmented by higher levels of phenylcoumarans and
      resinols. The C3H-deficient alfalfa lignins were devoid of beta-1 coupling
      products, highlighting the significant differences in the reaction course for p
      coumaryl alcohol versus the two normally dominant monolignols, coniferyl and
      sinapyl alcohols. A larger range of dibenzodioxocin structures was evident in
      conjunction with an approximate doubling of their proportion. The nature of each
      of the structural units was revealed by long range 13C-1H correlation
      experiments. For example, although beta-ethers resulted from the coupling of all
      three monolignols with the growing polymer, phenylcoumarans were formed almost
      solely from coupling reactions involving p-coumaryl alcohol; they resulted from
      both coniferyl and sinapyl alcohol in the wild-type plants. Such structural
      differences form a basis for explaining differences in digestibility and pulping
      performance of C3H-deficient plants.

PMID- 16421106
TI  - Modulation of chaperone function and cochaperone interaction by novobiocin in the
      C-terminal domain of Hsp90: evidence that coumarin antibiotics disrupt Hsp90
      dimerization.
AB  - The C-terminal domain of Hsp90 displays independent chaperone activity, mediates
      dimerization, and contains the MEEVD motif essential for interaction with
      tetratricopeptide repeat-containing immunophilin cochaperones assembled in mature
      steroid receptor complexes. An alpha-helical region, upstream of the MEEVD
      peptide, helps form the dimerization interface and includes a hydrophobic
      microdomain that contributes to the Hsp90 interaction with the immunophilin
      cochaperones and corresponds to the binding site for novobiocin, a coumarin
      related Hsp90 inhibitor. Mutation of selected residues within the hydrophobic
      microdomain significantly impacted the chaperone function of a recombinant C
      terminal Hsp90 fragment and novobiocin inhibited wild-type chaperone activity.
      Prior incubation of the Hsp90 fragment with novobiocin led to a direct blockade
      of immunophilin cochaperone binding. However, the drug had little influence on
      the pre-formed Hsp90-immunophilin complex, suggesting that bound cochaperones
      mask the novobiocin-binding site. We observed a differential effect of the drug
      on Hsp90-immunophilin interaction, suggesting that the immunophilins make
      distinct contacts within the C-terminal domain to specifically modulate Hsp90
      function. Novobiocin also precluded the interaction of full-length Hsp90 with the
      p50(cdc37) cochaperone, which targets the N-terminal nucleotide-binding domain,
      and is prevalent in Hsp90 complexes with protein kinase substrates. Novobiocin
      therefore acts locally and allosterically to induce conformational changes within
      multiple regions of the Hsp90 protein. We provide evidence that coumermycin A1, a
      coumarin structurally related to novobiocin, interferes with dimerization of the
      Hsp90 C-terminal domain. Coumarin-based inhibitors then may antagonize Hsp90
      function by inducing a conformation favoring separation of the C-terminal domains
      and release of substrate.

PMID- 16421109
TI  - Is the whole brain periventricular?

PMID- 16421108
TI  - A uracil-DNA glycosylase inhibitor encoded by a non-uracil containing viral DNA.
AB  - Uracil-DNA glycosylase (UDG) is an enzyme involved in the base excision repair
      pathway. It specifically removes uracil from both single-stranded and double
      stranded DNA. The genome of the Bacillus subtilis phage 29 is a linear double
      stranded DNA with a terminal protein covalently linked at each 5'-end.
      Replication of 29 DNA starts by a protein-priming mechanism and generates
      intermediates that have long stretches of single-stranded DNA. By using in vivo
      chemical cross-linking and affinity chromatography techniques, we found that UDG
      is a cellular target for the early viral protein p56. Addition of purified
      protein p56 to B. subtilis extracts inhibited the endogenous UDG activity.
      Moreover, extracts from 29-infected cells were deficient in UDG activity. We
      suggested that inhibition of the cellular UDG is a defense mechanism developed by
      29 to prevent the action of the base excision repair pathway if uracil residues
      arise in their replicative intermediates. Protein p56 is the first example of a
      UDG inhibitor encoded by a non-uracil-containing viral DNA.

PMID- 16421111
TI  - Cognitive profile in CADASIL patients.

PMID- 16421112
TI  - Major congenital malformations and antiepileptic drugs: prospective observations.

PMID- 16421113
TI  - Quality of life in dementia: more than just cognition. An analysis of
      associations with quality of life in dementia.
AB  - OBJECTIVES: To explore the extent to which commonly used measures of specific
      outcomes in dementia are an appropriate proxy for quality of life in dementia.
      METHODS: This was a cross sectional study set in communities in London and
      Nottingham, comprising 101 people with dementia and their 99 main family
      caregivers. The main outcome measures were health related quality of life in
      dementia (measured by the DEMQOL-Proxy), cognition (Mini Mental State
      Examination), functional impairment (Barthel Index), behavioural and
      psychological symptoms in dementia (Neuropsychiatric Inventory; NPI), and carer
      mental health (General Health Questionnaire). RESULTS: On univariate analysis,
      decreased quality of life was statistically significantly correlated with higher
      levels of behavioural and psychological disturbance (NPI total score and its
      agitation, depression, anxiety, disinhibition, and irritability subscales);
      younger age of the person with dementia; and poorer mental health of the carer.
      Quality of life was not statistically significantly associated with cognition or
      carer age. In a multivariate model, psychological and behavioural disturbance and
      patient age remained statistically significantly associated with quality of life.
      Carer mental health was no longer statistically significantly associated, and
      cognition and functional limitation remained statistically insignificant.
      CONCLUSIONS: These data suggest that quality of life in dementia is complex, and
      that simple proxy substitutions of discrete measures such as cognition or
      function are likely to miss important factors.

PMID- 16421114
TI  - Increase in periventricular white matter hyperintensities parallels decline in
      mental processing speed in a non-demented elderly population.
AB  - OBJECTIVE: To investigate the influence of deep white matter hyperintensities
      (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression
      of cognitive decline in non-demented elderly people. METHODS: All data come from
      the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly
      at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the
      PROSPER study using both repeated magnetic resonance imaging and cognitive
      testing. Cognitive decline and its dependency on WMH severity was assessed using
      linear regression models adjusted for sex, age, education, treatment group, and
      test version when applicable. RESULTS: We found that the volume of PVWMH at
      baseline was longitudinally associated with reduced mental processing speed (p =
      0.0075). In addition, we found that the progression in PVWMH volume paralleled
      the decline in mental processing speed (p = 0.024). In contrast, neither presence
      nor progression of DWMH was associated with change in performance on any of the
      cognitive tests. CONCLUSION: PVWMH should not be considered benign but probably
      underlie impairment in cognitive processing speed.

PMID- 16421116
TI  - Discriminative and predictive power of an informant report in mild cognitive
      impairment.
AB  - BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE) requires caregivers to rate decline in patients' cognitive and
      functional performance and has never been used for mild cognitive impairment
      (MCI). METHODS: We contrasted the discriminative and predictive power of the
      IQCODE with that of the Mini Mental State Examination (MMSE) and a verbal
      episodic memory measure, the Rey's Auditory Verbal Learning Test (RAVLT), in 45
      patients with MCI (mean (SD) age at baseline: 71.6 (4.7) years) and 30
      outpatients with dementia (70.5 (6.3) years) attending the Neuropsychology
      Service, St Gerardo Hospital, and compared them with 55 cognitively intact
      elderly people (70.7 (7.1) years). Patients with MCI were followed up for at
      least 2 years or until conversion to dementia. RESULTS: In total, 24 patients
      with MCI (53.3%) had converted to dementia at follow up (mean (SD) duration of
      follow up 17.0 (7.3) months for converters and 35.0 (7.1) months for non
      converters). At baseline, the ability to differentiate patients with MCI from
      healthy controls was similar for the IQCODE (area under the curve (AUC) 0.86) and
      the MMSE (AUC 0.84; z = 0.53, not significant). As predictors of conversion to
      dementia, a trend favouring the IQCODE (AUC 0.86) with respect to immediate (AUC
      0.74) and delayed (AUC 0.75) recall on the RAVLT was apparent (z = 1.36, p =
      0.087 versus immediate recall, z = 1.51, p = 0.064 versus delayed recall). The
      independent predictive ability of IQCODE and memory scores was evaluated through
      logistic regression, and the questionnaire alone yielded the best correct
      classification of 81%. CONCLUSIONS: The IQCODE is an informant based measure of
      cognitive decline that may provide a relevant contribution to the diagnostic and
      prognostic investigation of patients with MCI.

PMID- 16421115
TI  - The apolipoprotein E epsilon4 allele selectively increases the risk of
      frontotemporal lobar degeneration in males.
AB  - OBJECTIVE: To determine whether polymorphic variations in the apolipoprotein E
      gene (APOE) are associated with increased risk of frontotemporal lobar
      degeneration (FTLD) when mutation in tau gene is absent. METHODS: The APOE gene
      was genotyped by polymerase chain reaction from DNA routinely extracted from
      blood or brain tissues. The APOE epsilon4 allele frequency in 198 patients with
      FTLD not associated with mutations in tau gene was compared with that of a
      control group of 756 normal individuals drawn from the same geographical region.
      Analyses were done according to clinical subtype or sex. RESULTS: The APOE
      epsilon4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole
      control group (14.1%), while the APOE epsilon2 allele frequency in FTLD (6.5%)
      was slightly lower than in controls (8.0%) (NS). The APOE epsilon4 allele
      frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls
      (12.3%); the frequency in women (16.3%) was similar to that in female controls
      (14.8%) (NS). The APOE epsilon2 allele frequency in men with FTLD was 4.9% while
      in male controls it was 9.5% (p = 0.06), but there was no difference in women
      (7.5% v 7.9%, NS). Neither the APOE epsilon2 nor APOE epsilon4 allele frequency
      varied significantly between any of the clinical subtypes. CONCLUSIONS: In FTLD
      not associated with mutations in tau gene, possession of APOE epsilon4 allele in
      men roughly doubles the chances of developing disease, whereas this has no impact
      upon disease risk in women.

PMID- 16421117
TI  - Dyskinesias induced by subthalamotomy in Parkinson's disease are unresponsive to
      amantadine.
AB  - BACKGROUND: Dyskinesias are a transient but severe complication of subthalamotomy
      in some patients. PATIENTS AND METHODS: Three patients with Parkinson's disease
      undergoing bilateral micro-recording guided surgery of the subthalamic nucleus
      (STN) are described; deep brain stimulation (DBS) was used in one case, and
      subthalamotomy in the other two. Prior to surgery, levodopa induced dyskinesia
      had improved (< or = 50%) under treatment with amantadine (400 mg/day, po) in all
      three patients. The patient treated with DBS developed severe dyskinesia a few
      days after discharge and began self medication with amantadine but showed no
      improvement. This suggested a possible lack of response to amantadine for
      treatment of dyskinesias induced by surgery of the STN. RESULTS: Both patients
      treated with bilateral subthalamotomy developed unilateral choreoballistic
      movements immediately after surgery, despite not taking levodopa (L-dopa).
      Patients were scored using the dyskinesia scale and started treatment with 400 mg
      amantadine (po) for 4 days within the first postoperative week with no effect on
      dyskinesia score or its phenomenology. Amantadine was therefore discontinued. One
      month after surgery both patients were free of involuntary movements with an
      improvement of about 60% in the "off" state UPDRS motor score. Six month follow
      up showed maintained antiparkinsonian benefit, without need for levodopa
      treatment and complete absence of dyskinesia. CONCLUSION: The present findings
      suggest that: (i) amantadine probably exerts its anti-dyskinetic effect by acting
      on the "indirect" pathway; (ii) the pathophysiological mechanisms of
      subthalamotomy induced dyskinesias may differ from those involved in L-dopa
      induced dyskinesias; (iii) dyskinesias induced by STN surgery resolve
      spontaneously as compensatory mechanisms develop.

PMID- 16421118
TI  - Cognitive profile in CADASIL.
AB  - BACKGROUND: The spectrum of cognitive alterations associated with CADASIL, a
      model of pure vascular dementia, has not been thoroughly evaluated. OBJECTIVES:
      The aims of this study were: (i) to describe the cognitive profile in CADASIL
      patients according to age; (ii) to compare the profile of patients with dementia
      with that of patients without dementia; and (iii) to determine the association
      between alterations in performance in different cognitive domains. METHODS: Forty
      two consecutive individuals with CADASIL (35-73 years old) were investigated.
      Cognitive skills were analysed in five domains (executive functions, reasoning,
      attention, memory, visuospatial abilities) according to age and compared between
      patients with and without dementia. Associations between cognitive performance
      and stroke were tested. RESULTS: The youngest patients presented with attention
      (69%), memory (70%), and executive disturbances (100%). Visuospatial abilities
      and reasoning deteriorated with age, mainly after the age of 60. About one
      quarter of patients had dementia, and 75% of these were >60 years of age. Age >60
      years was associated with a Rankin score >3 and a significant deficit in all
      cognitive domains. No association was found between dementia and the number of
      ischaemic attacks. Episodic memory disorder was characterised by difficulties in
      retrieval rather than impairment of the encoding process. CONCLUSION: Cognitive
      decline in CADASIL is dominated by early impairment of executive functions.
      Skills in other cognitive domains deteriorate with age and are found to be
      diffusely impaired in patients with dementia. The relative preservation of the
      encoding process in episodic memory impairment, even in individuals with
      dementia, is noteworthy.

PMID- 16421119
TI  - Serum matrix metalloproteinase-3 levels correlate with disease activity in
      relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Adhesion molecules and matrix metalloproteinases (MMPs) are known to
      be relevant to the ongoing development and disappearance of areas of
      demyelination in the white matter of the CNS of multiple sclerosis (MS) patients.
      This study examined whether serum matrix metalloproteinase-3 (MMP-3) levels
      correlate with disease activity in MS. METHODS: Serum MMP-3 levels in 47
      consecutive patients with relapsing-remitting MS were measured by immunoassay
      every 4 weeks over a 15 month period. RESULTS: During the study period, 48
      clinical relapses occurred. Serum MMP-3 levels within 1 month of relapse were
      significantly higher than during the remission phase. Sequential analysis showed
      that serum MMP-3 levels had increased transiently at the time of clinical relapse
      but returned to the normal range within a month. CONCLUSIONS: Circulatory MMP-3
      levels are correlated with disease activity in relapsing-remitting MS. This may
      contribute to the breakdown of the blood-brain barrier at the time of relapse.

PMID- 16421120
TI  - Plasma homocysteine levels in multiple sclerosis.
AB  - BACKGROUND: There is evidence that homocysteine contributes to various
      neurodegenerative disorders, and elevated plasma homocysteine levels have been
      observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if
      and why plasma homocysteine levels are increased in MS, and whether they play a
      role in the disease course. METHODS: We compared plasma levels of homocysteine in
      88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign
      course, 37 were secondary progressive, and 23 primary progressive. To explore the
      underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate,
      interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide
      production, and plasma diene conjugate levels (measure of oxidative stress).
      RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8
      (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However,
      there were no significant differences in homocysteine levels between the three
      clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and
      folate were not different between patients with MS and controls. In the MS group,
      there were no correlations between plasma homocysteine levels and the serum
      concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or
      plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine occurs
      in both benign and progressive disease courses of MS, and seems unrelated to
      immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12,
      or folate.

PMID- 16421122
TI  - Neurological picture. Focal splenial hyperintensity in epilepsy.

PMID- 16421121
TI  - Sudden unexpected death in epilepsy (SUDEP): don't ask, don't tell?
AB  - BACKGROUND: The National Institute for Clinical Excellence in the UK has issued
      guidelines stating all individuals with epilepsy be given information about
      sudden unexpected death in epilepsy (SUDEP). METHODS: We conducted a survey of
      current practice among UK neurologists, using a questionnaire sent to all
      practising neurologists in the UK listed on the Association of British
      Neurologists database, asking under what circumstances they told patients about
      SUDEP. RESULTS: Of the validated respondents, 5% discussed SUDEP with all
      patients, 26% with a majority, 61% with a few, and 7.5% with none. The commonest
      reasons for SUDEP to be discussed were the patient asking about it and the
      neurologist counselling people with known risk factors for SUDEP. CONCLUSIONS:
      The variation we found, although not necessarily in tune with the guidelines,
      reflects the variation in patients' need for knowledge about their condition.

PMID- 16421123
TI  - Causes of death among patients with myasthenia gravis in Norway between 1951 and
      2001.
AB  - OBJECTIVE: This study investigated the causes of death among patients with
      myasthenia gravis (MG), with emphasis on respiratory tract and cardiac disease.
      METHODS: The Norwegian Cause of Death Register contains information on all deaths
      among Norwegian citizens. In total, 249 deceased patients with MG were identified
      (1951-2001). These were compared with 1245 controls deceased in the same period
      and matched for sex and year of birth. RESULTS: The death certificates of
      patients with MG had a significantly higher occurrence of respiratory tract
      disease as cause of death than controls (28.1% v 20.9%, p = 0.012). The
      difference was most pronounced for male patients, for patients dying between 30
      and 69 years of age, and for deaths occurring before 1996. For cardiac disease
      there was a significantly lower occurrence among patients with MG than among
      controls at 50-69 years of age, for both men (19.4% v 52.0%, p = 0.001) and women
      (14.6% v 29.6%, p = 0.036). Age and year of death were important determinants for
      the causes of death, but could not account for the differences between the
      patients with MG and controls. CONCLUSIONS: This study shows that patients with
      MG dying between 1951 and 1995 had a higher occurrence of respiratory tract
      disease listed as cause of death than had a matched control group. The lack of
      difference after 1995 probably reflects improved treatment of MG and its
      complications. The reduced occurrence of cardiac disease among patients with MG
      is probably explained by competing factors (respiratory tract disease) causing
      death.

PMID- 16421124
TI  - Neurological picture. Medial medullary infarction.

PMID- 16421125
TI  - Abnormal muscle responses in hemifacial spasm: F waves or trigeminal reflexes?
AB  - OBJECTIVE: In patients with hemifacial spasm (HFS), abnormal muscle responses
      (AMR) are frequently present. The objective of this study was to investigate
      whether the afferent input of AMR is mediated by antidromic facial nerve
      stimulation or orthodromic trigeminal nerve stimulation. METHODS: AMR in the
      orbicularis oris muscle were recorded in 28 patients with HFS. When AMR were
      present, they were recorded after subthreshold stimulation of the facial nerve
      and weak stimulation delivered to the skin. RESULTS: AMR were recordable in 24
      (86%) of the patients, and usually consisted of the early constant component
      (mean onset latency, 10.0 ms) and late variable component (35.3 ms), similar to
      R1 and R2 of the blink reflex. The early or late components of AMR, or both, were
      frequently elicited after subthreshold stimulation of the facial nerve (43%) and
      skin stimulation (88%). CONCLUSIONS: AMR are likely to be mediated by trigeminal
      afferent inputs, rather than antidromic activation of the facial nerve, and are a
      type of trigeminal reflex.

PMID- 16421126
TI  - Facial emotion recognition in myotonic dystrophy type 1 correlates with CTG
      repeat expansion.
AB  - OBJECTIVE: To investigate the ability of patients with myotonic dystrophy type 1
      to recognise basic facial emotions. We also explored the relationship between
      facial emotion recognition, neuropsychological data, personality, and CTG repeat
      expansion data in the DM-1 group. METHODS: In total, 50 patients with DM-1 (28
      women and 22 men) participated, with 41 healthy controls. Recognition of facial
      emotional expressions was assessed using photographs of basic emotions. A set of
      tests measured cognition and personality dimensions, and CTG repeat size was
      quantified in blood lymphocytes. RESULTS: Patients with DM-1 showed impaired
      recognition of facial emotions compared with controls. A significant negative
      correlation was found between total score of emotion recognition in a forced
      choice task and CTG repeat size. Furthermore, specific cognitive functions
      (vocabulary, visuospatial construction ability, and speed) and personality
      dimensions (reward dependence and cooperativeness) correlated with scores on the
      forced choice emotion recognition task. CONCLUSION: These findings revealed a CTG
      repeat dependent facial emotion recognition deficit in the DM-1 group, which was
      associated with specific neuropsychological functions. Furthermore, a correlation
      was found between facial emotional recognition ability and personality dimensions
      associated with sociability. This adds a new clinically relevant dimension in the
      cognitive deficits associated with DM-1.

PMID- 16421127
TI  - Peripheral neuropathies in Waldenstrom's macroglobulinaemia.
AB  - OBJECTIVE: We sought to determine the prevalence, clinical features, and
      laboratory characteristics of polyneuropathies in Waldenstrom's
      macroglobulinaemia (WM), a malignant bone marrow disorder with lymphocytes that
      produce monoclonal IgM. METHODS: We prospectively studied 119 patients with WM
      and 58 controls. Medical history was taken, and neurological examinations,
      electrodiagnostic tests, and serum studies were performed by different examiners
      who were blinded to results except the diagnosis of WM. RESULTS: Polyneuropathy
      symptoms, including discomfort and sensory loss in the legs, occurred more
      frequently (p<0.001) in patients with WM (47%) than in controls (9%). Patients
      with WM had 35% lower quantitative vibration scores, and more frequent pin loss
      (3.4 times) and gait disorders (5.5 times) than controls (all p<0.001). Patients
      with IgM binding to sulphatide (5% of WM) had sensory axon loss; those with IgM
      binding to myelin associated glycoprotein (MAG) (4% of WM) had sensorimotor axon
      loss and demyelination. Patients with WM with IgM binding to sulphatide (p<0.005)
      or MAG (p<0.001) had more severe sensory axon loss than other patients with WM.
      Demyelination occurred in 4% of patients with WM with no IgM binding to MAG. Age
      related reductions in vibration sense and sural SNAP amplitudes were similar (
      approximately 30%) in WM and controls. CONCLUSIONS: Peripheral nerve symptoms and
      signs occur more frequently in patients with WM than controls, involve sensory
      modalities, and are often associated with gait disorders. IgM binding to MAG or
      sulphatide is associated with a further increase in the frequency and severity of
      peripheral nerve involvement. Age related changes, similar to those in controls,
      add to the degree of reduced nerve function in patients with WM.

PMID- 16421129
TI  - Cognition in the days following concussion: comparison of symptomatic versus
      asymptomatic athletes.
AB  - BACKGROUND: Concussion is a common neurological injury occurring during contact
      sport. Current guidelines recommend that no athlete should return to play while
      symptomatic or displaying cognitive dysfunction. This study compared post
      concussion cognitive function in recently concussed athletes who were
      symptomatic/asymptomatic at the time of assessment with that of non-injured
      (control) athletes. METHODS: Prospective study of 615 male Australian Rules
      footballers. Before the season, all participants (while healthy) completed a
      battery of baseline computerised (CogSport) and paper and pencil cognitive tasks.
      Sixty one injured athletes (symptomatic = 25 and asymptomatic = 36) were
      reassessed within 11 days of being concussed; 84 controls were also reassessed.
      The serial cognitive function of the three groups was compared using analysis of
      variance. RESULTS: The performance of the symptomatic group declined at the post
      concussion assessment on computerised tests of simple, choice, and complex
      reaction times compared with the asymptomatic and control groups. The magnitude
      of changes was large according to conventional statistical criteria. On paper and
      pencil tests, the symptomatic group displayed no change at reassessment, whereas
      large improvements were seen in the other two groups. CONCLUSION: Injured
      athletes experiencing symptoms of concussion displayed impaired motor function
      and attention, although their learning and memory were preserved. These athletes
      displayed no change in performance on paper and pencil tests in contrast with the
      improvement observed in asymptomatic and non-injured athletes. Athletes
      experiencing symptoms of concussion should be withheld from training and
      competition until both symptoms and cognitive dysfunction have resolved.

PMID- 16421128
TI  - Radiological findings in individuals at high risk of psychosis.
AB  - OBJECTIVE: To assess the prevalence of radiological magnetic resonance imaging
      (MRI) findings in individuals at high risk of schizophrenia. METHODS: MRI scans
      from individuals at high risk of schizophrenia (HR; n = 37) were assessed by a
      radiologist blind to group status and compared with scans from patients with
      first episode psychosis (FE; n = 30), depressive controls (DC; n = 17), and
      healthy controls (HC; n = 26). RESULTS: There was a significantly higher
      proportion of radiological findings in individuals at high risk of schizophrenia
      (35%) and patients with first-episode psychosis (40%) than in patients with
      depression (18%) or healthy controls (12%). These differences were specific to
      findings regarded as potentially clinically significant as opposed to normal
      variants; however, there was no indication for medical treatment. CONCLUSIONS:
      The results suggest that a large proportion of those at high risk of psychosis
      have radiological findings on MRI scanning, and that the prevalence of
      radiological findings in this group is similar to that in patients with first
      episode psychosis.

PMID- 16421130
TI  - CSF biomarkers in frontotemporal lobar degeneration: relations with clinical
      characteristics, apolipoprotein E genotype, and neuroimaging.
AB  - In order to better understand the large variation in cerebrospinal fluid (CSF)
      tau and amyloid-beta(1-42) (Abeta42) in frontotemporal lobar degeneration (FTLD),
      relations between these biomarkers and clinical parameters, neuroimaging
      characteristics, and apolipoprotein E (ApoE) genotype were studied in 31 patients
      with FTLD, including 16 patients with the frontal variant and 15 with the
      temporal variant. CSF tau was highest in FTLD with predominant temporal
      involvement. In the frontal subgroup, CSF tau level was influenced by the number
      of ApoE epsilon3 alleles. In the temporal subgroup, CSF tau level was dependent
      on a combination of CSF Abeta42, age, disease duration, and disease severity. No
      relation with degree of atrophy or asymmetry on neuroimaging could be
      established. CSF Abeta42 variability remained unexplained. Future research could
      study the role of ApoE genotype and Abeta42 in FTLD, as well as establish
      measures for disease intensity.

PMID- 16421131
TI  - Measuring therapy adherence in Parkinson's disease: a comparison of methods.
AB  - The objective of this study was to assess different methods of measuring therapy
      adherence in Parkinson's disease (PD). In a single centre observational study,
      112 patients with idiopathic PD were randomised to a crossover trial of active
      monitoring (n = 69, simple tablet count and electronic monitoring), or to no
      monitoring (n = 43, control group). All patients completed a self report and
      visual analogue scale (VAS) indicating therapy intake. In the active monitoring
      group, 56 (81% of cases) used > or = 80% of their medication, and 13 (19% of
      cases) used <80%, based on electronic monitoring. Median adherence for self
      report was 100% (interquartile range (IQR) 100 to 100) and for VAS was 100% (IQR
      95 to 100), in both active and control groups. Patients taking > or = 80% of
      prescribed medication had a median total adherence of 98% (IQR 93 to 101) by
      electronic monitoring, which was similar to that from other METHODS: self report
      100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; simple tablet count 98%, IQR 89 to
      100. Median total adherence in patients taking <80% of medication was
      significantly lower by electronic monitoring (69%, IQR 44 to 74) than by other
      methods: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; and simple
      tablet count 90%, IQR 78 to 100 (all p<0.0001). Sensitivities of self report
      (10%), VAS (17%), and simple tablet count (50%) were all low for detecting
      suboptimal medicine intake. Self report, VAS, and simple tablet counts are
      insensitive as predictors of suboptimal medicine usage in PD. How patients take
      their medicines influences interpretation of the therapy response and consequent
      management decisions, with implications for clinical trial analysis and clinical
      practice.

PMID- 16421132
TI  - A family study on primary blepharospasm.
AB  - BACKGROUND: Previous family studies provided evidence that blepharospasm (BSP)
      can aggregate in families but did not give accurate and reliable information on
      the characteristics and degree of familial clustering. AIM: To evaluate the
      proportion of familial and non-familial BSP cases, the clinical expression of
      dystonia within families, the inheritance pattern, and the extent of penetrance.
      METHODS: The study was based on the examination of the first degree relatives of
      56 probands with primary BSP. RESULTS: The 56 families produced a potential
      population of 436 first degree relatives of whom 296 were alive and 233 were
      examined. The proportion of index patients with at least one first degree
      relative affected by BSP, or adult onset dystonia other than BSP, was 27%. There
      was a remarkable degree of phenotypic variability of dystonia within families.
      Similar segregation ratios were calculated for probands' siblings and children.
      Under the assumption of autosomal dominant transmission of adult onset dystonia,
      penetrance was about 20%. CONCLUSIONS: The findings of this family study are
      relevant for accurately counselling the families of patients with BSP and may
      help identify the most appropriate study design to explore genetic susceptibility
      in BSP.

PMID- 16421134
TI  - Multiple sclerosis in stepsiblings: recurrence risk and ascertainment.
AB  - Reports implicating specific transmissible agents in multiple sclerosis (MS)
      susceptibility continue to appear. We therefore re-evaluated MS risk in 687 step
      siblings of 19 746 MS index cases. We found the risk of MS to be
      indistinguishable from that of the general population after diagnostic
      verification. These results are coherent with studies of adopted children, half
      siblings and conjugals, showing no risk attributable to the familial
      microenvironment. This family based genetic epidemiological approach found no
      trace of transmissibility other than genetic from one affected individual to
      another in the high prevalence area of Canada. This adds to existing data showing
      that the action of environment in influencing MS risk is operative at a
      population level.

PMID- 16421133
TI  - Paradoxical response of VEGF expression to hypoxia in CSF of patients with ALS.
AB  - Vascular endothelial growth factor (VEGF) is implicated in motor neurone
      degeneration. In normal individuals, hypoxia is known to induce an overexpression
      of VEGF, as measured in CSF. We show that patients with ALS do not manifest this
      VEGF overexpression in the presence of hypoxia. Although VEGF gene expression is
      mainly stimulated by hypoxia, we have measured lower VEGF levels in cerebrospinal
      fluid (CSF) from hypoxaemic patients with amyotrophic lateral sclerosis (ALS)
      than in CSF from normoxaemic patients with ALS. In contrast, hypoxaemic
      neurological controls displayed higher levels than normoxaemic neurological
      controls. There was a negative correlation between VEGF levels and the severity
      of hypoxaemia in patients with ALS, suggesting deregulation of VEGF in ALS.

PMID- 16421135
TI  - Optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos
      disease).
AB  - A fatal case of malignant atrophic papulosis (Degos disease) with optic nerve and
      spinal cord involvement is described. Magnetic resonance imaging (MRI) of the
      optic nerve showed abnormal signal enhancement on fat suppressed T1 weighted
      images after intravenous meglumine gadopentetate infusion. On T2 weighted
      sagittal images, a sawtooth pattern was observed over seven vertebral segments of
      the spinal cord. On necropsy, a severe loss of myelinated nerve fibres in the
      left optic nerve was seen, with thrombotic obstruction of the central retinal
      artery. Spongy degeneration was observed in all levels of the spinal cord, with
      patchy and motheaten patterns caused by thromboses and endothelial proliferation
      in subarachnoid vessels. Findings on MRI were consistent with findings on
      pathological examination.

PMID- 16421136
TI  - Incidence of common compressive neuropathies in primary care.
AB  - Apart from carpal tunnel syndrome, there are no population based studies of the
      epidemiology of compressive neuropathies. To provide this information, new
      presentations of compressive neuropathies among patients registered with 253
      general practices in the UK General Practice Research Database with 1.83 million
      patient years at risk in 2000 were analysed. The study revealed that in 2000 the
      annual age standardised rates per 100 000 of new presentations in primary care
      were: carpal tunnel syndrome, men 87.8/women 192.8; Morton's metatarsalgia, men
      50.2/women 87.5; ulnar neuropathy, men 25.2/women 18.9; meralgia paraesthetica,
      men 10.7/women 13.2; and radial neuropathy, men 2.97/women 1.42. New
      presentations were most frequent at ages 55-64 years except for carpal tunnel
      syndrome, which was most frequent in women aged 45-54 years, and radial nerve
      palsy, which was most frequent in men aged 75-84 years. In 2000, operative
      treatment was undertaken for 31% of new presentations of carpal tunnel syndrome,
      3% of Morton's metatarsalgia, and 30% of ulnar neuropathy.

PMID- 16421137
TI  - Ptosis aggravates dysphagia in oculopharyngeal muscular dystrophy.
AB  - BACKGROUND: Ptosis and dysphagia are important features in oculopharyngeal
      muscular dystrophy (OPMD). OBJECTIVE: Retroflexion of the head is a well known
      compensatory mechanism for ptosis, but generally retroflexion has a negative
      effect on swallowing. We hypothesised that severity of ptosis is related to
      degree of retroflexion and that this compensation is responsible for
      deteriorating dysphagia. METHODS: Nine OPMD patients were examined in the
      conditions "head position adapted to ptosis" and "head position slightly flexed".
      Ptosis was quantified by photogrammetry and retroflexion of the head by digital
      photographs. The severity of dysphagia was measured using visual analogue scales
      (VAS) and by calculating swallowing volumes and oropharyngeal swallow efficiency
      (OPSE) based on videofluoroscopy. RESULTS: Statistical analyses show a
      significant relationship between ptosis and degree of retroflexion. The degree of
      retroflexion of the head correlated significantly with VAS scores and with the
      maximum swallowing volume. The slightly flexed head position significantly
      improved VAS scores as well as swallowing volumes and OPSE. CONCLUSION: In OPMD
      patients, ptosis significantly correlates with retroflexion of the head, which
      has a negative effect on swallowing. Subjective and objective reduction of
      swallowing problems was found when patients were instructed to eat and drink with
      a slightly flexed head position.

PMID- 16421138
TI  - A case of multiple cutaneous schwannomas; schwannomatosis or neurofibromatosis
      type 2?
AB  - A 54 year old man presented with numerous cutaneous schwannomas, cranial nerve
      lesions, and spinal cord lesions, but no evidence of vestibular nerve
      involvement. There was no family history of neurocutaneous lesions. To help
      discriminate between the various possible diagnoses in this patient, molecular
      analysis of two cutaneous schwannomas was undertaken. An identical point mutation
      in the NF2 gene in the two anatomically distinct tumours was found, confirming
      this as a case of NF2 mosaicism.

PMID- 16421139
TI  - Clinical relevance of memory performance during Wada is stimulus type dependent.
AB  - OBJECTIVES: This study aimed to investigate whether different types of memory
      stimulus provide different information during the Wada or intracarotid amytal
      procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE).
      METHODS: Eighty nine surgical candidates with documented MTLE and selected for
      left hemispheric language dominance underwent memory assessment with verbal and
      dually encodable stimuli during a presurgical IAP. RESULTS: The overall IAP
      memory performance with the left hemisphere is significantly better than with the
      right hemisphere regardless of lesion side. This can be explained by the left
      hemispheric advantage of encoding all stimuli, whereas the right hemisphere has
      only limited resources to encode verbal stimuli. More importantly, it appeared
      that dually encodable items remain more readily recognised following injection
      ipsilateral to the lesion, whereas verbal items are always better recognised
      following right hemisphere injection regardless of lesion side. CONCLUSIONS:
      Verbal IAP stimuli show left hemispheric sensitivity in left language dominant
      MTLE patients. The dually encodable items of the IAP appear lesion sensitive.

PMID- 16421140
TI  - Heterogeneity of Parkinson's disease.

PMID- 16421141
TI  - A case of post-traumatic isolated ACTH deficiency with spontaneous recovery 9
      months after the event.

PMID- 16421142
TI  - An aspirin responsive non-progressive chronic chorea.

PMID- 16421143
TI  - Interaction between dopamine beta-hydroxylase and interleukin genes increases
      Alzheimer's disease risk.

PMID- 16421144
TI  - A third eye for the surgeon.

PMID- 16421145
TI  - Interleukin 1beta-511 C/T polymorphism and risk of aneurysmal subarachnoid
      haemorrhage.

PMID- 16421146
TI  - A novel sacsin mutation in a Japanese woman showing clinical uniformity of
      autosomal recessive spastic ataxia of Charlevoix-Saguenay.

PMID- 16421147
TI  - Qualitative evidence of anti-Ri specific intrathecal antibody synthesis and
      quantification of anti-Ri antibodies in serial samples from a patient with anti
      Ri syndrome.

PMID- 16421148
TI  - Parkinsonism and dementia due to gliomatosis cerebri mimicking sporadic
      Creutzfeldt-Jakob disease (CJD).

PMID- 16421149
TI  - Case reports of suspected adverse drug reactions--systematic literature survey of
      follow-up.
AB  - OBJECTIVE: To determine whether anecdotal reports of suspected adverse drug
      reactions are valuable early warning signals. DESIGN: Systematic literature
      survey DATA SOURCES: We evaluated all case reports of adverse drug reactions
      published in 1997 in five medical journals. Reports were excluded if the adverse
      reaction had previously been described in earlier publications and was already
      listed in the product information of the drug reference source (the British
      National Formulary (BNF) or the Medicines Compendium). We used the Web of
      Knowledge Citation Index and Medline for 2003 to identify follow-up studies. MAIN
      OUTCOME MEASURES: Primary: the number of suspected adverse reactions subjected to
      formal validation studies and the findings of these studies. Secondary: the
      number of instances in which the warning from the case report was incorporated
      into the product information. RESULTS: We evaluated 63 suspected adverse
      reactions and found that most (52/63, 83%) had not yet been subjected to further
      detailed evaluation. Data from controlled studies that supported the postulated
      link between the drug and the adverse event were available in only three cases.
      Of the 48 agents listed in the drug reference sources, details of the suspected
      reaction were subsequently added to the Medicines Compendium in 15 instances, and
      to the BNF in seven instances. In each case, only one reaction had been
      confirmed. CONCLUSIONS: Published case reports of suspected adverse reactions are
      of limited value as suspicions are seldom subjected to confirmatory
      investigation. Furthermore, these alerts are not incorporated into drug reference
      sources in a systematic manner.

PMID- 16421150
TI  - A man with a serum creatinine near 10 mg/dl with an intravenous pyelogram showing
      normally functioning kidneys.

PMID- 16421151
TI  - Renal extraction of cystatin C vs 125I-iothalamate in hypertensive patients.
AB  - BACKGROUND: Several markers are available to estimate the glomerular filtration
      rate (GFR) in patients. Cystatin C is a relatively new marker and has been
      suggested as an alternative for creatinine. Numerous studies have been performed
      to evaluate the usefulness of cystatin C to estimate GFR. The aim of this study
      is to compare the renal extraction of cystatin C with that of 125I-iothalamate in
      hypertensive patients. METHODS: Forty hypertensive patients with unilateral renal
      artery stenosis, and who used at least two antihypertensive agents, were studied.
      For the determination of the renal extraction ratio, blood samples were drawn
      simultaneously from the renal vein and the abdominal aorta. The renal extraction
      ratio was calculated as ([A]-[V])/[A], in which A is the plasma concentration of
      the compound from the abdominal aorta, and V is the plasma concentration of the
      compound from the renal vein. RESULTS: The mean difference between the renal
      extraction ratio of cystatin C and that of 125I-iothalamate was 0.002. The 95%
      confidence interval (CI) for the mean difference was -0.036 to 0.032, which was
      not statistically significant. However, the limits of agreement were large (
      0.271 and 0.267). CONCLUSIONS: Despite a lower reported glomerular sieving
      coefficient of cystatin C, the mean renal extraction of cystatin C was equal to
      the mean renal extraction of 125I-iothalamate in hypertensive patients,
      suggesting tubular secretion of cystatin C. Combined with the large variation in
      the renal extraction of cystatin C, these findings cast doubts on its usefulness
      as a glomerular filtration marker.

PMID- 16421152
TI  - Videolaparoscopy as rescue therapy and placement of peritoneal dialysis
      catheters: a thirty-two case single centre experience.
AB  - BACKGROUND: Malfunction of the peritoneal catheter is a frequent complication in
      peritoneal dialysis (PD). Videolaparoscopy is a minimal invasive technique that
      allows rescue therapy of malfunctioning catheters and consecutive immediate
      resumption of PD. Furthermore, Tenckhoff catheters can be safely positioned in
      patients with previous abdominal surgery. We analysed the clinical diagnosis,
      videolaparoscopic treatment and the outcome of PD patients on whom
      videolaparoscopic interventions had been performed at our centre. METHODS: Thirty
      two cases of videolaparoscopic interventions were performed for salvage of
      malfunctioning peritoneal catheters, implantation and abdominal surgical
      interventions in 25 PD patients. The videolaparoscope was inserted through a mini
      laparotomy site of 15 mm diameter which was closed with purse-string sutures at
      the end of the intervention. RESULTS: Videolaparoscopy was used in 21 cases of
      catheter malfunction mostly due to omental wrapping (12 cases) and dislocation
      (five cases). In eight patients with previous surgical abdominal interventions,
      laparoscopic placement of the PD catheter was performed. In two cases the gall
      bladder was removed. One case of intestinal occlusion was evaluated
      laparoscopically in an attempt to minimize invasive surgery. Leakage of the
      peritoneal fluid presented the only complication caused by insufficient closure
      of one mini-laparotomy site. Minimal follow-up time of rescued catheters was 5
      months. Videolaparoscopy prolonged PD catheter function by a median of 163 days
      (range 5-1469 days). CONCLUSIONS: Videolaparoscopy prolongs peritoneal catheter
      survival by treating directly the causes of malfunction. In patients with
      preceding abdominal interventions, the PD catheter can be placed safely even in
      cases necessitating surgical preparation like adhesiolysis.

PMID- 16421153
TI  - Non-association of VEGF genetic polymorphisms in promoter--5' UTR with end-stage
      renal disease.

PMID- 16421154
TI  - Fatal relapse of thrombotic thrombocytopaenic purpura after cardiac surgery in
      patient with congenital absence of vWF-cleaving protease activity.

PMID- 16421155
TI  - A new treatment for polyarteritis nodosa.

PMID- 16421156
TI  - Is salt-wasting the long awaited answer to the hyperuricaemia seen in uromodulin
      storage diseases?

PMID- 16421157
TI  - Favourable outcomes in episodes of Pseudomonas bacteraemia when associated with
      tunnelled cuffed catheters (TCCs) in chronic haemodialysis patients.
AB  - BACKGROUND: Pseudomonas is regarded as a particularly lethal bacterial isolate.
      High mortality rates have been reported in episodes of Pseudomonas sepsis when
      associated with visceral infections as seen in immunosuppressed, hospitalized
      patients. In comparison, lower mortality rates have been reported with catheter
      associated Pseudomonas bacteraemia in non-dialysis patients. The purpose of this
      study was to determine the risk factors and the outcomes for episodes of
      Pseudomonas bacteraemia associated with the use of tunnelled cuffed haemodialysis
      catheters (TCCs) in a chronic out-patient population. METHODS: We performed a
      prospective observational study in seven chronic haemodialysis units over a 2.5
      year period. Patients who were diagnosed as having their initial TCC-associated
      bacteraemia within the study period were followed for 3 months. All episodes of
      Pseudomonas TCC bacteraemia were identified, and univariate analyses were
      performed to compare Pseudomonas bacteraemia with non-Pseudomonas bacteraemia.
      RESULTS: During the study period, 219 episodes of TCC bacteraemia were
      identified; 18 had a Pseudomonas isolate (8%). Pseudomonas bacteraemia episodes
      were associated with a significantly higher risk of not receiving appropriate
      initial antibiotics (odds ratio = 3.6, P = 0.02). There were no deaths in the
      Pseudomonas bacteraemia group, whereas 19% died in the non-Pseudomonas group. The
      TCC was removed in 89% of Pseudomonas bacteraemias. There were no significant
      risk factors for acquiring a Pseudomonas isolate, and no difference in recurrent
      bacteraemia or infectious complication rates between the groups. CONCLUSIONS: In
      haemodialysis patients with a TCC-associated Pseudomonas bacteraemia, outcomes
      are remarkably good. This may be because the source of Pseudomonas infection was
      removed in most cases. Initial antibiotic coverage lacking anti-Pseudomonas
      activity was not associated with increased mortality.

PMID- 16421158
TI  - Effects of low molecular weight heparin in obstructed kidneys: decrease of
      collagen, fibronectin and TGF-beta, and increase of chondroitin/dermatan sulfate
      proteoglycans and macrophage infiltration.
AB  - BACKGROUND: Heparin exerts beneficial effects in different experimental models of
      nephropathy, as observed by the preservation of the structural morphology of the
      kidney after heparin therapy. Here we investigate molecular and cellular events
      involved in the protective effects of heparin in the progression of renal disease
      after unilateral ureteral obstruction. METHODS: Thirty-six rats were divided into
      six groups: group C (control) was not subjected to any surgical manipulation;
      group S (sham) was subjected to surgical manipulation but without ureteral
      ligation; group UUO was subjected to ureteral obstruction and received no
      treatment; group UUO + S was subjected to ureteral obstruction and received
      saline subcutaneously (s.c.) once daily; group UUO + H was subjected to ureteral
      obstruction and received low molecular weight heparin (LMW-Hep; 4 mg/kg) s.c.
      once daily; and group C + H was not subjected to any surgical manipulation and
      received LMW-Hep (4 mg/kg) s.c. once daily. After 14 days, the content of
      collagen, fibronectin, total glycosaminoglycans (GAGS), chondroitin
      sulfate/dermatan sulfate proteoglycans (CS/DSPGs), transforming growth factor
      beta (TGF-beta) and cellular infiltration were determined in the kidneys by
      immunohistochemical and biochemical techniques. RESULTS: Collagen, fibronectin,
      total GAGS, CS/DSPGs, TGF-beta and cellular infiltration increased significantly
      in group UUO. LMW-Hep treatment reduced collagen, fibronectin and TGF-beta, but
      induced an increase in the content of total GAGS, CS/DSPGs and macrophage
      infiltration in group UUO + H when compared with group UUO. CONCLUSIONS: LMW-Hep
      diminishes fibrosis in obstructed kidneys by downregulating the synthesis of
      collagen, fibronectin and TGF-beta. The mechanisms underlying the overproduction
      of CS/DSPGs and the increase in cellular infiltration upon LMW-Hep administration
      remain to be elucidated.

PMID- 16421159
TI  - Expression of the chemokine receptor CXCR3 in human renal allografts--a
      prospective study.
AB  - BACKGROUND: Mechanisms involved in the recruitment and activation of inflammatory
      cells during renal allograft injury are still incompletely understood. Since
      chemokines play pivotal roles in this process, our prospective study was
      performed to evaluate further the role of the chemokine receptor CXCR3. METHODS:
      A total of 138 biopsies were included from patients without rejection and
      unaltered morphology (according to Banff 97 classification grade 1, n = 49), with
      acute interstitial rejection (Banff grade 4 type I, n = 8), with acute vascular
      rejection (Banff grade 4 type II, n = 23), with chronic allograft nephropathy
      (Banff grade 5, n = 16), without rejection but with various other lesions (Banff
      grade 6, n = 36) and from pre-transplant kidneys (n = 6). The expression of CXCR3
      , CD4- and CD8-positive cells was localized by immunohistochemistry and
      quantified by image analysis. RESULTS: CXCR3 was expressed by infiltrating
      inflammatory cells, but not by intrinsic renal structures. CXCR3-positive cells
      were found to be involved in tubulitis and vascular rejection. The area of CXCR3
      positive staining was significantly larger in biopsies with acute interstitial
      rejection (P<0.001) and acute vascular rejection (P<0.001) as compared with
      normal renal graft biopsies. There was a strong morphological and numerical
      correlation between CXCR3 and both CD4- and CD8-positive T cells, respectively.
      CONCLUSIONS: A significant part of both CD4- and CD8-positive T cells express the
      chemokine receptor CXCR3. During renal allograft rejection, the number of these
      cells increases significantly at the site of injury and might be targeted by
      CXCR3 blocking agents.

PMID- 16421160
TI  - Impact of upper extremity abduction on arteriovenous fistula (AVF) blood flow.

PMID- 16421161
TI  - Association of low blood pressure with increased mortality in patients with
      moderate to severe chronic kidney disease.
AB  - BACKGROUND: Blood pressure shows an inverse association with mortality in
      patients with chronic kidney disease (CKD) on dialysis. It is unclear if the same
      phenomenon exists in patients with CKD not yet on dialysis. METHODS: We examined
      the association of systolic (SBP) and diastolic (DBP) blood pressure with all
      cause mortality in a historical prospective cohort of 860 patients (age 68.1+/
      10.1 years, 99.1% male, 24.4% black) with estimated glomerular filtration rate
      (GFR) < 60 ml/min/1.73 m2. We used Cox models to adjust for the effects of age,
      race, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD),
      congestive heart failure, smoking, antihypertensive medications, body mass index,
      GFR, albumin, cholesterol, haemoglobin and proteinuria. To examine the role of
      comorbidities, we performed subgroup analyses based on prevalent ASCVD status and
      level of estimated GFR. RESULTS: Higher SBP and higher DBP were both associated
      with lower mortality [adjusted hazard ratio (95% confidence interval) for SBP 133
      154, 155-170 and > 170 mmHg, compared with < 133 mmHg, respectively: 0.61 (0.44
      0.85), 0.62 (0.45-0.87) and 0.68 (0.49-0.96); and for DBP 65-75, 76-86 and > 86
      mmHg, compared with < 65 mmHg: 0.85 (0.62-1.18), 0.72 (0.52-1.00) and 0.60 (0.41
      0.86)]. The same association was present for both SBP and DBP only in subgroups
      with GFR < or = 30 ml/min/1.73 m2 and for DBP only in the subgroup with ASCVD.
      CONCLUSIONS: Lower blood pressure is associated with higher mortality in patients
      with moderate to severe CKD, but interactions with kidney function and with ASCVD
      suggest that blood pressure may play a surrogate rather than a causative role in
      this association.

PMID- 16421162
TI  - Diltiazem suppresses collagen synthesis and IL-1beta-induced TGF-beta1 production
      on human peritoneal mesothelial cells.
AB  - BACKGROUND: After long-term treatment with continuous ambulatory peritoneal
      dialysis (CAPD), some patients may develop peritoneal fibrosis. Peritoneal
      mesothelial cells (PMCs) participate in the inflammatory reactions in the
      peritoneal cavity, and transforming growth factor-beta1 (TGF-beta1) and
      interleukin-1beta (IL-1beta) are involved in peritoneal fibrosis. Diltiazem is
      used frequently in patients with CAPD to treat hypertension. The objectives of
      this study were to examine the effects of diltiazem on collagen- and IL-1beta
      induced TGF-beta1 production on human PMCs and the signalling pathway of
      diltiazem in this induction. METHODS: Human PMCs were cultured from the enzymatic
      disaggregation of human omentum. Collagen synthesis was measured by [3H]proline
      incorporation into pepsin-resistant, salt-precipitated collagen. The expression
      of collagen I and III, and TGF-beta1 mRNA was evaluated by northern blotting. The
      production of TGF-beta1 by human PMCs was measured by immunoassay. The changes of
      intracellular calcium level after adding Fura-2-AM were measured by fluorescence
      spectrophotometry. Western blotting was used to assess mitogen-activated protein
      kinase (MAPK) signalling proteins. RESULTS: We found that diltiazem (<0.2 mM)
      inhibited collagen I and III mRNA expression and collagen syntheses on a dose
      dependent basis. Diltiazem (0.2 mM) suppressed IL-1beta- (5 ng/ml) induced TGF
      beta1 production on human PMCs at both the protein and mRNA levels. Diltiazem
      (0.2 mM) also inhibited IL-1beta- (5 ng/ml) induced collagen I and III mRNA
      expression. Intracellular calcium levels did not change after the treatment with
      diltiazem, IL-1beta or both. The IL-1beta-treated human PMCs increased phospho
      JNK (stress-activated c-Jun N-terminal kinase) and phospho-p38 MAPK expression,
      while diltiazem could suppress this phenomenon. CONCLUSIONS: Diltiazem suppressed
      collagen synthesis of human PMCs and inhibited IL-1beta-induced TGF-beta1
      production on human PMCs. This signalling transduction may be through p38 MAPK
      and JNK pathways instead of intracellular calcium. These results suggest
      diltiazem to be a potential therapeutic regimen in preventing peritoneal fibrosis
      and support further in vivo studies.

PMID- 16421163
TI  - PAF-acetylhydrolase activity in plasma of patients with chronic kidney disease.
      Effect of long-term therapy with erythropoietin.
AB  - BACKGROUND: Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+
      independent phospholipase A2 that is secreted mainly from monocytes/macrophages.
      In human plasma, PAF-AH is associated primarily with low-density lipoprotein
      (LDL), while a small proportion of enzyme is associated with high-density
      lipoprotein (HDL). The ratio of HDL-PAF-AH to total plasma enzyme activity may
      represent a potential marker of atherogenicity. We evaluated possible alterations
      of lipoprotein-associated enzyme activity in Chronic Kidney Disease (CKD)
      patients, stages 3-4, and further investigated whether long-term therapy with
      recombinant human erythropoietin (epoetin) has any influence on the plasma PAF-AH
      activity in vivo or on the enzyme activity secreted from peripheral blood
      monocytes (PBMs), in vitro. METHODS: Forty-eight patients, 28 men and 20 women,
      with CKD (stages 3-4) participated in the study. Patients were randomized into
      groups I and II. Patients of group I (n = 28) were administered subcutaneously
      epoetin, 50 units/kg once per week. The Hb target was 13 g/dl. In group II (n =
      20), epoetin was initiated only when the Hb levels decreased during follow-up to
      less than 9 g/dl. All patients were seen on an outpatient basis at 2, 4 and 6
      months. Twenty-two normolipidemic age- and sex-matched healthy volunteers also
      participated in the study and were used as controls. RESULTS: The PAF-AH activity
      in plasma of both patient groups at baseline was higher compared to controls,
      whereas no difference in the HDL-PAF-AH activity was observed among the studied
      groups. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was
      significantly lower in both patient groups compared to controls. Epoetin
      administration in the patients of group I was associated with a significant
      increase in the plasma PAF-AH and in HDL-PAF-AH activities 2 months after
      treatment, which remained stable for up to 6 months of therapy, a phenomenon not
      observed in untreated patients of group II. Thus, the ratio of HDL-PAF-AH to the
      plasma enzyme activity was significantly increased in patients of group I
      compared to the baseline values, a phenomenon not observed in patients of group
      II. In vitro treatment with epoetin of PBMs from patients of group I (undergoing
      therapy with epoetin) resulted in a dose-dependent increase in total and secreted
      enzyme activity, a phenomenon not observed in patients of group II who did not
      receive therapy with epoetin. This suggests that the in vivo increase in
      lipoprotein-associated PAF-AH observed in patients treated with epoetin may be
      attributed to the drug-induced enhanced secretion of PAF-AH from PBMs of these
      patients. CONCLUSIONS: CKD patients of stages 3-4 are characterized by an
      increase in plasma PAF-AH activity and a low ratio of HDL-PAF-AH to total plasma
      enzyme activity. Long-term therapy with epoetin may improve this atherogenic
      ratio thus this drug may play an important antiatherogenic role in CKD.

PMID- 16421164
TI  - Aberrant expression of SPARC and its impact on proliferation and apoptosis in
      ADPKD cyst-lining epithelia.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) results from a
      combination of environmental and genetic factors. Secreted protein acidic and
      rich in cysteine (SPARC) can be expressed by many different cell types and is
      associated with development, remodelling, cell turnover and tissue repair. The
      analysis of SPARC would help evaluate the effect of the unique matricellular
      glycoprotein on renal disease progression in ADPKD. METHODS: The concentration of
      SPARC was measured with an enzyme-linked immunosorbent assay (ELISA);
      distribution and expression levels were measured with in situ hybridization,
      immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR)
      and western blot assays. Apoptosis was assessed by morphological observation and
      fluorescence-activated cell sorting (FACS) apoptosis index (AI) analysis. Cell
      cycle phase was examined by FACS analysis. Cell proliferation was studied using
      bromodeoxyuridine (BrdU) incorporation ELISA. RESULTS: The SPARC level in the
      renal cyst fluid of patients with ADPKD was greater than that in patients with
      simple renal cyst (SRC), and also greater than that found in the plasma and urine
      of patients with either ADPKD or SRC and normal subjects. SPARC mRNA and protein
      levels in polycystic renal tissue were greater than that in normal renal tissue.
      Additionally, SPARC could inhibit cyst-lining epithelial cell proliferation,
      bring about cell cycle arrest in the G0/G1 phase and induce apoptosis in vitro.
      SPARC treatment resulted in decreased mRNA levels of PCNA (proliferating cell
      nuclear antigen), MCM2 (minichromosome maintenance protein 2), ClnD1 and Bcl-2,
      but an increased mRNA level of p21(Waf1) in cyst-lining epithelial cells.
      CONCLUSION: Our findings suggest that the increased SPARC expression in ADPKD
      renal tissue may provide negative feedback in ADPKD patients.

PMID- 16421165
TI  - Correlates of habitual physical activity in chronic haemodialysis patients.
AB  - BACKGROUND: Results of physical performance tests may not reflect the level of
      habitual physical activity and health status of the dialysis patients. The aim of
      our study was to assess interdialytic spontaneous physical activity in chronic
      haemodialysis (HD) patients in relation to their nutritional status, severity of
      anaemia, inflammation and dialysis adequacy. METHODS: Sixty HD patients [27
      female, 33 male; mean age 60+/-13 years, time on dialysis 46.2+/-62.1 months and
      body mass index (BMI) 25.1+/-4.7 kg/m2] without physical and neurological
      disabilities and 16 healthy individuals (10 female, six male, mean age 56+/-6
      years, BMI 26.6+/-4.9 kg/m2) were enrolled into the study. In all patients,
      spontaneous daily physical activity was measured during 48 h between mid-week
      dialysis sessions by pedometers. Nutritional status was estimated by
      anthropometric methods (BMI and mid-arm muscle circumference) and serum albumin
      concentration. Additionally, body composition was estimated using a
      multifrequency phase-sensitive bioimpedance analysis (BIA). Severity of anaemia
      was determined by blood haemoglobin level and haematocrit value, and the presence
      of inflammatory state was determined by high sensitivity plasma C-reactive (CRP)
      protein measurements. RESULTS: The total number of steps during daily activities
      in dialysis patients and in healthy individuals was 6896+/-2357 vs 14 181+/-5383
      per 48 h, respectively (P<0.001). Dialysis patients showed typical signs of
      malnutrition in the BIA, i.e. high extracellular mass/body cell mass index
      (1.17+/-0.28 in dialysis patients vs 0.97+/-0.1 in controls; P<0.001), low
      percentage cell mass (46.7+/-5.6 and 51.0+/-3.6, respectively; P = 0.002) and low
      phase angle (5.1+/-0.9 and 5.8+/-0.7, respectively; P = 0.006). Dialysis patients
      also showed lower serum albumin and blood haemoglobin and higher serum CRP levels
      than healthy controls. In dialysis patients, the number of steps taken positively
      correlated with body water (R = 0.28, P = 0.03), fat mass (r = 0.29, P = 0.04),
      BMI (R = 0.25, P = 0.04), lean body mass (R = 0.26, P = 0.04), intracellular
      water (r = 0.30, P<0.01), phase angle (R = 0.40, P = 0.002), serum albumin (R =
      0.32, P = 0.01), haematocrit (R = 0.46, P = 0.001) and haemoglobin (R = 0.44, P =
      0.001). Furthermore, the number of steps taken correlated significantly with mid
      arm muscle circumference (r = 0.35, P = 0.006). A negative correlation was found
      between the number of steps and extracellular mass/body cell mass index (R = 
      0.37; P = 0.004). No significant relationships were found between the measures of
      physical activity and high sensitivity CRP or adequacy of dialysis. Multiple
      regression analysis revealed the independent associations between the number of
      steps taken by the patients and haemoglobin concentration, age, total body water,
      extracellular mass/body cell mass index and phase angle. CONCLUSIONS: Low
      habitual physical activity assessed in HD patients with simple portable
      pedometers is strongly related to several factors of major clinical importance in
      this population.

PMID- 16421166
TI  - Tacrolimus combined with mycophenolate mofetil can effectively reverse C4d
      positive steroid-resistant acute rejection in Chinese renal allograft recipients.
AB  - BACKGROUND: Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) has been
      suggested to play a critical role in the reversal of C4d-positive acute humoral
      rejection (AHR) in renal transplantation, but the efficacy of using only TAC-MMF
      without immunoadsorption or plasmapheresis has not been investigated. On the
      other hand, Chinese recipients of renal grafts usually need lower doses of
      immunosuppressants, and their optimal treatment for acute humoral rejection has
      not been established. METHODS: Since 1999, we have used TAC-MMF to treat steroid
      resistant acute rejection (AR). C4d staining was retrospectively performed in 32
      patients with steroid-resistant AR, and the treatments of 19 patients with C4d
      positive steroid-resistant AR were investigated. RESULTS: Thirteen of 19 patients
      received TAC-MMF treatment only; 11 episodes of rejection in them were reversed
      (7 completely, 4 partially) and only 2 recipients lost their graft. Another 6
      patients received immunoadsorption also. One of them failed to respond and lost
      her graft. Four of 5 patients treated with immunoadsorption and TAC-MMF recovered
      (3 completely, 1 partially), but 3 of them had severe pneumonia, a complication
      rate statistically higher than in patients treated with only TAC-MMF (P<0.05). AR
      occurring during the first two weeks after transplantation had a statistically
      better outcome than that occurring later (P = 0.003). CONCLUSION: Our study
      suggests that the combination of TAC and MMF is a potentially safe and economic
      treatment for most Chinese renal allograft recipients with C4d-positive steroid
      resistant AR, especially for rejections developing within the first two weeks
      after transplantation.

PMID- 16421167
TI  - A dry mouth and oedematous ankle.

PMID- 16421168
TI  - Structural stability and chromosome-specific telomere length is governed by cis
      acting determinants in humans.
AB  - Single telomere length analysis (STELA) of the XpYp telomere has revealed
      extensive allelic variation and ultra-short telomeres in senescent cells.
      Superimposed on end-replication losses are additional mutational events that
      result in large-scale changes in telomere length. In order to establish if the
      dynamics of the XpYp telomere are typical of human telomeres, here we describe an
      analysis using STELA of the telomeres of 2p, 11q, 12q, 17p and XpYp. The dynamics
      of telomere loss (erosion rates and stochastic length changes) was conserved
      among 2p, 11q, 12q and XpYp within the same cell strains and was dependent on the
      replicative kinetics of the cells in culture. However, of the telomeres analysed,
      the telomere of 17p was more stable with a striking paucity of large-scale length
      changes, and exhibited the shortest recorded allelic distribution (300 bp) in
      senescent cells and displayed a general, but not absolute, trend towards being
      the shortest telomere. Ectopic over-expression of hTERT homogenized both allelic
      and chromosome-specific telomeric distributions. However, telomerase-expressing
      cancer cells displayed both allelic variation and chromosome-specific telomere
      length, with 17p displaying the shortest allelic telomere length. Although other
      telomeres in the genome may share the properties of 17p, these data suggest that
      physiological levels of telomerase allow differential telomere length regulation
      and indicate the presence of cis-acting factors that govern both telomeric
      stability and chromosome-specific telomere length in the presence of telomerase.

PMID- 16421169
TI  - Allele-specific deposition of macroH2A1 in imprinting control regions.
AB  - In the current study, we analyzed the deposition patterns of macroH2A1 at a
      number of different genomic loci located in X chromosome and autosomes. MacroH2A1
      is preferentially deposited at methylated CpG-rich regions located close to
      promoters. The macroH2A1 deposition patterns at the methylated CpG islands of
      several imprinted domains, including the imprinting control regions (ICRs) of
      Xist, Peg3, H19/Igf2, Gtl2/Dlk1 and Gnas domains, show consistent allele
      specificity towards inactive, methylated alleles. The macroH2A1 deposition levels
      at the ICRs and other differentially methylated regions of these domains are also
      either higher or comparable to those observed at the inactive X chromosome of
      female mammals. Overall, our results indicate that besides DNA methylation
      macroH2A1 is another epigenetic component in the chromatin of ICRs displaying
      differential association with two parental alleles.

PMID- 16421170
TI  - Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2
      (Igf2) locus.
AB  - IGF2 loss of imprinting (LOI) is fairly prevalent and implicated in the
      pathogenesis of human cancer and developmental disease; however, the causes of
      this phenomenon are largely unknown. We determined whether the post-weaning diet
      of mice affects allelic expression and CpG methylation of Igf2. C57BL/6JxCast/EiJ
      F1 hybrid mice were weaned onto (1) a standard natural ingredient control diet,
      (2) a synthetic control diet or (3) a synthetic methyl-donor-deficient diet
      lacking folic acid, vitamin B(12), methionine and choline. Maternal Igf2
      expression in kidney was negligible at birth, but increased to approximately 10%
      of total expression after 60 days on the natural control diet. By 60 days post
      weaning, both synthetic diets caused significant LOI of Igf2 relative to animals
      weaned onto the natural control diet. Total Igf2 expression was significantly
      reduced in these groups, however, indicating that the increase in relative
      maternal Igf2 expression was caused by specific down-regulation of the paternal
      allele. The LOI induced by the synthetic-deficient diet persisted during a
      subsequent 100-day 'recuperation' period on natural ingredient diet. There were
      no group differences in overall or allele-specific CpG methylation in the H19
      differentially methylated region (DMR), Igf2 DMR0 or Igf2 DMR1. At 30 and 60 days
      post-weaning, however, the paternal allele of Igf2 DMR2 was hypermethylated in
      the kidneys of mice on the control synthetic diet. These results indicate that
      post-weaning diet can permanently affect expression of Igf2, suggesting that
      childhood diet could contribute to IGF2 LOI in humans.

PMID- 16421172
TI  - Comparison of 19 pre-operative risk stratification models in open-heart surgery.
AB  - AIMS: To compare 19 risk score algorithms with regard to their validity to
      predict 30-day and 1-year mortality after cardiac surgery. METHODS AND RESULTS:
      Risk factors for patients undergoing heart surgery between 1996 and 2001 at a
      single centre were prospectively collected. Receiver operating characteristics
      (ROC) curves were used to describe the performance and accuracy. Survival at 1
      year and cause of death were obtained in all cases. The study included 6222
      cardiac surgical procedures. Actual mortality was 2.9% at 30 days and 6.1% at 1
      year. Discriminatory power for 30-day and 1-year mortality in cardiac surgery was
      highest for logistic (0.84 and 0.77) and additive (0.84 and 0.77) European System
      for Cardiac Operative Risk Evaluation (EuroSCORE) algorithms, followed by
      Cleveland Clinic (0.82 and 0.76) and Magovern (0.82 and 0.76) scoring systems.
      None of the other 15 risk algorithms had a significantly better discriminatory
      power than these four. In coronary artery bypass grafting (CABG)-only surgery,
      EuroSCORE followed by New York State (NYS) and Cleveland Clinic risk score showed
      the highest discriminatory power for 30-day and 1-year mortality. CONCLUSION:
      EuroSCORE, Cleveland Clinic, and Magovern risk algorithms showed superior
      performance and accuracy in open-heart surgery, and EuroSCORE, NYS, and Cleveland
      Clinic in CABG-only surgery. Although the models were originally designed to
      predict early mortality, the 1-year mortality prediction was also reasonably
      accurate.

PMID- 16421173
TI  - The CAREGENE study: polymorphisms of the beta1-adrenoceptor gene and aerobic
      power in coronary artery disease.
AB  - AIMS: The heritability of aerobic power and of the response to physical training
      has been shown in healthy subjects. beta(1)-Adrenergic receptor (beta(1)AR)
      function affects exercise performance. This study aims to investigate whether the
      Ser49Gly and Gly389Arg polymorphisms of the beta(1)AR gene or their haplotypes
      are associated with aerobic power or its response to physical training in
      coronary artery disease (CAD). METHODS AND RESULTS: Nine hundred and thirty-five
      biologically unrelated Caucasian patients with CAD who had exercised until
      exhaustion during graded bicycle testing at baseline and after completion of 3
      months of exercise training from 1990 to 2001 (n = 1095) were eligible for
      inclusion in the CAREGENE (CArdiac REhabilitation and GENetics of Exercise
      performance) study. Polymorphisms were detected using the invader assay (Third
      Wave Technologiestrade mark, Madison, Wisconsin, USA). Patients with the Gly49Gly
      genotype had significantly higher covariate-adjusted aerobic power at baseline
      than those with Ser49Ser and Ser49Gly (P < 0.05). Adjusted aerobic power at
      baseline was highest in the Ser49-Gly389/Gly49-Gly389 and Gly49-Arg389/Gly49
      Arg389 haplotype combinations. Aerobic power increased significantly (P < 0.001)
      with physical training. There was no association with the effect of physical
      training. CONCLUSION: Ser49Gly and haplotype combinations of Ser49Gly and
      Gly389Arg of the beta(1)AR gene are associated with aerobic power, but not with
      the response to physical training in patients with CAD included in the CAREGENE
      study.

PMID- 16421171
TI  - Motor system activation after subcortical stroke depends on corticospinal system
      integrity.
AB  - Movement-related brain activation patterns after subcortical stroke are
      characterized by relative overactivations in cortical motor areas compared with
      controls. In patients able to perform a motor task, overactivations are greater
      in those with more motor impairment. We hypothesized that recruitment of motor
      regions would shift from primary to secondary motor networks in response to
      impaired functional integrity of the corticospinal system (CSS). We measured the
      magnitude of brain activation using functional MRI during a motor task in eight
      chronic subcortical stroke patients. CSS functional integrity was assessed using
      transcranial magnetic stimulation to obtain stimulus/response curves for the
      affected first dorsal interosseus muscle, with a shallower gradient representing
      increasing disruption of CSS functional integrity. A negative correlation between
      the gradient of stimulus/response curve and magnitude of task-related brain
      activation was found in several motor-related regions, including ipsilesional
      posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior
      primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor
      area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional
      superior cingulate sulcus. There were no significant positive correlations in any
      brain region. These results suggest that impaired functional integrity of the CSS
      is associated with recruitment of secondary motor networks in both hemispheres in
      an attempt to generate motor output to spinal cord motoneurons. Secondary motor
      regions are less efficient at generating motor output so this reorganization can
      only be considered partially successful in reducing motor impairment after
      stroke.

PMID- 16421174
TI  - Prognostic significance of plasma osteopontin levels in patients with chronic
      stable angina.
AB  - AIMS: Levels of the secreted glycophosphoprotein osteopontin (OPN) have been
      associated with the presence and extent of coronary artery disease (CAD). The
      present study assessed the relationship between plasma OPN concentrations and
      prognosis in patients with chronic stable angina (CSA). METHODS AND RESULTS: OPN
      was measured in baseline plasma samples from 799 patients with stable angina
      pectoris and angiographically documented CAD. Participants were prospectively
      followed-up for a median of 2.7 years (maximum 4.1 years). The primary study
      endpoint was the composite of non-fatal myocardial infarction and death from
      cardiovascular causes. In the univariate Cox proportional hazard analysis, the
      log-transformed OPN level [hazard ratio (HR) 1.79, 95% CI 1.35-2.36, P < 0.001]
      was significantly related to adverse outcome. In addition, hypertension, levels
      of C-reactive protein, and statin use were associated with future adverse events.
      Levels of OPN (HR, 1.88; P < 0.001) and C-reactive protein (HR, 1.42; P = 0.003),
      as well as the presence of hypertension (HR, 2.39; P = 0.008) remained
      statistically significant, independent predictors of adverse cardiovascular
      outcome in a multivariable Cox proportional hazard analysis. CONCLUSION: Baseline
      levels of OPN are an independent predictor of future adverse cardiac events in
      patients with CSA and may be useful for risk stratification.

PMID- 16421175
TI  - Clinical predictors and prognostic significance of electrical storm in patients
      with implantable cardioverter defibrillators.
AB  - AIMS: Insufficient data exists regarding predictors of electrical storms (ES) and
      clinical outcome in patients treated with an implantable cardioverter
      defibrillator (ICD). The purpose of this study was to delineate a subgroup of
      patients likely to experience ES and to determine the impact of ES on mortality
      in ICD recipients. METHODS AND RESULTS: Baseline characteristics of 307 ICD
      treated patients were retrospectively analysed. ES was defined as two or more
      ventricular tachyarrhythmias within 24 h leading to an immediate electrical
      therapy (antitachycardia pacing and/or shock), separated by a period of sinus
      rhythm. Clinical characteristics and survival of 123 patients experiencing a
      total of 294 episodes of ES (median 2 ES/patient, range 1-9), were compared with
      those of 184 ES-free patients during a median follow-up of 826 days (inter
      quartile 1141 days). Median actuarial duration for the first ES occurrence after
      ICD implant was 1417 days [95% confidence interval (CI) 1061-2363] with a median
      follow-up of 816 days (7-4642 days) in ES-free patients. Univariate analysis
      identified older age, depressed left ventricular ejection fraction (LVEF),
      ventricular tachycardia (VT) as index arrhythmia, chronic renal failure and
      absence of lipid-lowering drugs as variables significantly associated with an
      increased risk of ES. Multivariable Cox analysis confirmed an independent
      predictive value for chronic renal failure [hazard ratio (HR) 1.54, 95% CI 0.95
      2.51, P=0.052], VT (HR 2.20, 95% CI 1.44-3.37, P=0.0003), and LVEF (HR 0.98, 95%
      CI 0.97-0.99, P=0.027). In contrast, diabetics (HR 0.49, 95% CI 0.27-0.90,
      P=0.022) were less affected by ES. There was no difference in survival between
      both groups. CONCLUSION: ES is frequent but does not increase mortality in ICD's
      recipients. Patients with severe systolic dysfunction, chronic renal failure and
      VT as initial arrhythmia are likely to experience ES. Diabetics are less affected
      by ES.

PMID- 16421176
TI  - An analysis of signatures of selective sweeps in natural populations of the house
      mouse.
AB  - Population and locus-specific reduction of variability of polymorphic loci could
      be an indication of positive selection at a linked site (selective sweep) and
      therefore point toward genes that have been involved in recent adaptations.
      Analysis of microsatellite variability offers a way to identify such regions and
      to ask whether they occur more often than expected by chance. We studied four
      populations of the house mouse (Mus musculus) to assess the frequency of such
      signatures of selective sweeps under natural conditions. Three samples represent
      the subspecies Mus m. dometicus [corrected] and came from Germany, France, and
      Cameroon. One sample came from Kazakhstan and constitutes a population of the
      subspecies Mus m. [corrected] musculus. Mitochondrial D-loop sequences from all
      animals confirm their respective assignments. Approximately 200 microsatellite
      loci were typed for up to 60 unrelated individuals from each population and
      evaluated for signs of selective sweeps on the basis of Schlotterer's ln RV and
      ln RH statistics. Our data suggest that there are slightly more signs of
      selective sweeps than would have been expected by chance alone in each of the
      populations and also highlights some of the statistical challenges faced in
      genome scans for detecting selection. Single-nucleotide polymorphism typing of
      one sweep signature in the M. m. domesticus populations around the beta-defensin
      6 locus confirms a lowered nucleotide diversity in this region and limits the
      potential sweep region to about 20 kb. However, no amino acid exchange has
      occurred in the coding region when compared to M. m. musculus. If this sweep
      signature is due to a recent adaptation, it is expected that a regulatory change
      would have caused it. Our data provide a framework for conducting a systematic
      whole genome scan for signatures of selective sweeps in the mouse genome.

PMID- 16421177
TI  - Dithiol compounds at low concentrations increase arsenite toxicity.
AB  - Inorganic trivalent arsenicals are vicinal thiol-reacting agents, and
      dithiothreitol (DTT) is a well-known dithiol agent. Interestingly, both
      decreasing and increasing effects of DTT on arsenic trioxide-induced apoptosis
      have been reported. We now provide data to show that, at high concentrations,
      DTT, dimercaptosuccinic acid (DMSA), and dimercaptopropanesulfonic acid (DMPS)
      decreased arsenic trioxide-induced apoptosis in NB4 cells, a human promyelocytic
      leukemia cell line. In contrast, at low concentrations DTT, DMSA, and DMPS
      increased the arsenic trioxide-induced apoptosis. DTT at a high concentration (3
      mM) decreased, whereas at a low concentration (0.1 mM), it increased the cell
      growth inhibition of arsenic trioxide, methylarsonous acid (MMA(III)), and
      dimethylarsinous acid (DMA(III)) in NB4 cells. DMSA and DMPS are currently used
      as antidotes for acute arsenic poisoning. These two dithiol compounds also show
      an inverse-hormetic effect on arsenic toxicity in terms of DNA damage,
      micronucleus induction, apoptosis, and colony formation in experiments using
      human epithelial cell lines derived from arsenic target tissues such as the
      kidney and bladder. With the oral administration of dithiols, the concentrations
      of these dithiol compounds in the human body are likely to be low. Therefore, the
      present results suggest the necessity of reevaluating the therapeutic effect of
      these dithiol compounds for arsenic poisoning.

PMID- 16421178
TI  - Trichloroethylene: mechanisms of renal toxicity and renal cancer and relevance to
      risk assessment.
AB  - 1,1,2-Trichloroethylene (TCE) is an important solvent that is widespread in the
      environment. We have reviewed carcinogenicity data from seven bioassays with
      regard to renal injury and renal tumors. We report a consistent but low incidence
      of renal tubule carcinoma in male rats. Epidemiology studies on workers exposed
      to TCE (and other chlorinated solvents) indicate a weak association between high
      level exposure and renal cancer. There appears to be a threshold below which no
      renal injury or carcinogenicity is expected to arise. TCE is not acutely
      nephrotoxic to rats or mice, but subchronic exposure to rats produces a small
      increase in urinary markers of renal injury. Following chronic exposure,
      pathological changes (toxic nephrosis and a high incidence of cytomegaly and
      karyomegaly) were observed. The basis for the chronic renal injury probably
      involves bioactivation of TCE. Based on the classification by E. A. Lock and G.
      C. Hard (2004, Crit. Rev. Toxicol. 34, 211-299) of chemicals that induce renal
      tubule tumors, we found no clear evidence to place TCE in category 1 or 2
      (chemicals that directly or indirectly interact with renal DNA), category 4
      (direct cytotoxicity and sustained tubule cell regeneration), category 5
      (indirect cytotoxicity and sustained tubule cell regeneration associated with
      alpha2u-globulin accumulation), or category 6 (exacerbation of spontaneous
      chronic progressive nephropathy). TCE is best placed in category 3, chemicals
      that undergo conjugation with GSH and subsequent enzymatic activation to a
      reactive species. The implication for human risk assessment is that TCE should
      not automatically be judged by linear default methods; benchmark methodology
      could be used.

PMID- 16421179
TI  - Single and combination toxic metal exposures induce apoptosis in cultured murine
      podocytes exclusively via the extrinsic caspase 8 pathway.
AB  - Arsenite, cadmium, and mercury are among the most abundant toxic metals (TM) in
      the environment. Although the most common renal manifestation of TM toxicity is
      proximal tubular dysfunction, significant glomerular injury can also occur. We
      hypothesized that glomerular injury following TM exposure results from TM-induced
      apoptosis of podocytes. To test this hypothesis we examined the extent of
      apoptosis and the apoptotic pathways induced in cultured murine podocytes
      incubated for three days with arsenite, cadmium, or mercury, and with equimolar
      combinations of all three metals. Apoptosis was detected by DNA laddering, and
      the number of apoptotic nuclei determined by Tunel assay. Treatment for three
      days with each TM resulted in DNA laddering and induced a dose-dependent increase
      in apoptotic nuclei. In contrast, treatment with equimolar combinations of TM
      induced significantly fewer apoptotic nuclei than individual TM treatments.
      Apoptosis induced by each TM was associated with a significant (approximately
      400%) increase in caspase 8 activity, but no change in caspase 9 activity, and
      Western analyses revealed a marked up-regulation of Fas (approximately 500%) and
      FADD (approximately 300%) with no change in expression of Bax, Bcl-2, or Bcl-xL.
      Similar to the apoptotic response, combinations of TM induced less caspase 8
      activity and Fas/FADD expression than individual TM treatments. Collectively,
      these results demonstrate that (1) TM induced apoptosis in cultured murine
      podocytes via the extrinsic Fas-FADD caspase 8 pathway, rather than the
      mitochondrial apoptotic pathway, and (2) combination TM exposure induced less
      apoptosis than individual TM, indicating an antagonistic rather than an additive
      or synergistic toxicity.

PMID- 16421180
TI  - Post-fall syndrome: a matter to study in patients with hip fractures admitted to
      orthopaedic wards.

PMID- 16421181
TI  - Health-related quality of life and depression among older people in Yerevan,
      Armenia: a comparative survey of retirement home and household residents aged 65
      years old and over.

PMID- 16421182
TI  - Cytomegalovirus colitis--an unusual cause for diarrhoea in an elderly woman.
AB  - BACKGROUND: Clinically apparent cytomegalovirus (CMV) disease is uncommon in the
      immunocompetent host, despite the high seroprevalence rate of CMV in the general
      population. CASE REPORT: Here, we report the case of CMV colitis in an
      immunocompetent elderly woman who developed a large pulmonary embolism during her
      illness. DISCUSSION: The diagnosis of CMV colitis is made on histological
      examination of biopsy specimens obtained at sigmoidoscopy or colonoscopy.
      Extensive CMV disease can be accompanied by vascular thrombosis.

PMID- 16421183
TI  - Senior physicians' estimates of the likely effects of feeding policies on
      outcomes prior to the completion of the FOOD trials.

PMID- 16421184
TI  - Computer modelling study of the mechanism of optic nerve injury in blunt trauma.
AB  - AIM: The potential causes of the optic nerve injury as a result of blunt object
      trauma, were investigated using a computer model. METHODS: A finite element model
      of the eye, the optic nerve, and the orbit with its content was constructed to
      simulate blunt object trauma. We used a model of the first phalanx of the index
      finger to represent the blunt body. The trauma was simulated by impacting the
      blunt body at the surface between the globe and the orbital wall at velocities
      between 2-5 m/s, and allowing it to penetrate 4-10 mm below the orbital rim.
      RESULTS: The impact caused rotations of the globe of up to 5000 degrees /s,
      lateral velocities of up to 1 m/s, and intraocular pressures (IOP) of over 300 mm
      Hg. The main stress concentration was observed at the insertion of the nerve into
      the sclera, at the side opposite to the impact. CONCLUSIONS: The results suggest
      that the most likely mechanisms of injury are rapid rotation and lateral
      translation of the globe, as well as a dramatic rise in the IOP. The strains
      calculated in the study should be sufficiently high to cause axonal damage and
      even the avulsion of the nerve. Finite element computer modelling has therefore
      provided important insights into a clinical scenario that cannot be replicated in
      human or animal experiments.

PMID- 16421185
TI  - Visual function and quality of life following vitrectomy and epiretinal membrane
      peel surgery.
AB  - AIM: To investigate the effect of epiretinal membrane (ERM) peel on patients'
      health related quality of life (HR-QOL) and to explore the association between
      self reported HR-QOL and conventional measures of visual function. METHODS: The
      National Eye Institute 25 Item Visual Function Questionnaire (VFQ-25) and the 36
      Item Short-Form Health Survey (SF-36) were self administered by 20 patients
      before and 4 months following surgery. Preoperative and postoperative data
      collected included logMAR near and distant visual acuity (VA), contrast
      sensitivity, and metamorphopsia. Questionnaire scores were compared
      preoperatively and postoperatively and their correlation with traditional methods
      of visual function evaluation analysed. RESULTS: Postoperatively there was no
      significant improvement in mean logMAR VA. However, eight (40%) subjects improved
      by two or more ETDRS lines and nine eyes (45%) reached a final VA of 6/18 or
      better. Metamorphopsia decreased significantly (p = 0.019) and there was
      significant improvement in VFQ-25 mean scores for the general vision (p = 0.03),
      distance activities (p = 0.05), and composite score (p = 0.03). Baseline
      binocular VA was significantly correlated with baseline VFQ-25 composite score (r
      = 0.631, p = 0.004). CONCLUSIONS: ERM surgery appears to improve patients'
      subjective perception of visual function as indicated by higher composite scores
      in VFQ-25 and improved metamorphopsia in the absence of significant improvement
      in mean logMAR VA.

PMID- 16421186
TI  - Double masked randomised controlled trial to assess the effectiveness of
      paracetamol in reducing pain in panretinal photocoagulation.
AB  - AIM: To assess the effectiveness of pre-emptive analgesia with paracetamol in
      reducing pain associated with panretinal photocoagulation (PRP) in a prospective,
      double masked, randomised controlled trial. METHOD: 60 patients undergoing PRP
      for the first time were enrolled and randomised to paracetamol or placebo, taken
      for 2 days starting 24 hours before the laser treatment. The laser treatment was
      performed following a standardised protocol. Pain during and after treatment was
      assessed using the McGill pain questionnaire (MPQ) and visual analogue scales
      (VAS). RESULTS: The statistical analysis looked for differences between the two
      study groups immediately after the laser surgery and 24 hours later. There was no
      statistically significant difference in the primary outcome measure of perception
      of pain during and 24 hours after PRP, between the paracetamol and placebo group.
      However, none of the patients in the paracetamol group reported increased total
      pain at 24 hours, whereas six patients in the placebo group reported increased
      pain; this difference (21%) was significant to p = 0.01. CONCLUSIONS: Pre-emptive
      analgesia with paracetamol did not significantly reduce pain associated with PRP.
      This study has described for the first time the type of pain associated with PRP,
      which is perceived mainly as a discomfort. The main attributes of the pain that
      patients described, were sharp, flashing, tiring, intense, piercing,
      intermittent, and brief.

PMID- 16421187
TI  - Perceived quality of reproductive care for girls in a competitive voucher
      programme. A quasi-experimental intervention study, Managua, Nicaragua.
AB  - OBJECTIVE: To determine whether female adolescents from low-income areas in
      Managua were satisfied with the sexual and reproductive health (SRH) care
      provided through a competitive voucher programme and to analyse the determinants
      of their satisfaction. DESIGN: A community-based quasi-experimental intervention
      study from 2000 to 2002. SETTING: Low-income areas of Managua. INTERVENTION:
      Distribution of 28,711 vouchers giving adolescents free-access to SRH care in 19
      clinics; training and support for health care providers. STUDY PARTICIPANTS: A
      random sample of 3009 girls from 12 to 20 years completed self-administered
      questionnaires: 700 respondents had used this care in the last 15 months, 221
      with voucher (users-with-voucher) and 479 without voucher (users-without
      voucher). MAIN OUTCOME MEASURES: User satisfaction; Satisfaction with clinic
      reception; Clarity of doctors' explanations. RESULTS: User satisfaction was
      significantly higher in users-with-voucher compared with users-without-voucher
      [Adjusted odds-ratio (AOR) = 2.2; 95% confidence interval (95% CI) = 1.2-4.0].
      Voucher use was associated with more frequent satisfaction with clinic reception,
      especially among sexually active girls not yet pregnant or mother (AOR = 6.9; 95%
      CI = 1.5-31.8). The clarity of doctors' explanations was not perceived
      differently (AOR = 1.4; 95% CI = 0.9-2.2). User satisfaction was highly
      correlated to satisfaction with clinic reception and clarity of doctors'
      explanations (P < 0.001). Longer consultation times, shorter waiting times, older
      age, and having a female doctor positively influenced user satisfaction.
      CONCLUSION: Voucher use by teenage girls was associated with a better perceived
      SRH care. This is an important result, given the crucial role user satisfaction
      plays in adoption and continued use of health care and contraceptives. Though
      more research is needed, confidential and guaranteed access appear key factors to
      voucher success.

PMID- 16421188
TI  - Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation.
AB  - Parathyroid hormone-related protein (PTHrP) is essential to maintain a pool of
      dividing, immature chondrocytes in the growth plate of long bones. In chick and
      mouse, expression of Nkx3.2/Bapx1 in the growth plate is restricted to the
      proliferative zone and is down regulated as chondrocyte maturation begins.
      Nkx3.2/Bapx1 expression is lost in the growth plates of mice engineered to lack
      PTHrP signaling and, conversely, is maintained by ectopic expression of PTHrP in
      developing bones. Artificially preventing Nkx3.2/Bapx1 downregulation, by forced
      expression of either retroviral-encoded PTHrP or Nkx3.2 inhibits chondrocyte
      maturation. Although wild-type Nkx3.2 blocks chondrocyte maturation by acting as
      a transcriptional repressor, a ;reverse function' mutant of Nkx3.2 that has been
      converted into a transcriptional activator conversely accelerates chondrocyte
      maturation. Nkx3.2 represses expression of the chondrocyte maturation factor
      Runx2, and Runx2 mis-expression can rescue the Nkx3.2-induced blockade of
      chondrocyte maturation. Taken together, these results suggest that PTHrP signals
      block chondrocyte hypertrophy by, in part, maintaining the expression of
      Nkx3.2/Bapx1, which in turn represses the expression of genes required for
      chondrocyte maturation.

PMID- 16421189
TI  - Developmental control of nuclear morphogenesis and anchoring by charleston,
      identified in a functional genomic screen of Drosophila cellularisation.
AB  - Morphogenesis of epithelial tissues relies on the precise developmental control
      of cell polarity and architecture. In the early Drosophila embryo, the primary
      epithelium forms during cellularisation, following a tightly controlled genetic
      programme where specific sets of genes are upregulated. Some of them, for
      example, control membrane invagination between the nuclei anchored at the apical
      surface of the syncytium. We used microarrays to describe the global programme of
      gene expression underlying cellularisation and identified distinct classes of
      upregulated genes during this process. Fifty-seven genes were then tested
      functionally by RNAi. We found six genes affecting various aspects of cellular
      architecture: membrane growth, organelle transport or organisation and junction
      assembly. We focus here on charleston (char), a new regulator of nuclear
      morphogenesis and of apical nuclear anchoring. In char-depleted embryos, the
      nuclei fail to maintain their elongated shape and, instead, become rounded. In
      addition, together with a disruption of the centrosome-nuclear envelope
      interaction, the nuclei lose their regular apical anchoring. These nuclear
      defects perturb the regular columnar organisation of epithelial cells in the
      embryo. Although microtubules are required for both nuclear morphogenesis and
      anchoring, char does not control microtubule organisation and association to the
      nuclear envelope. We show that Char is lipid anchored at the nuclear envelope by
      a farnesylation group, and localises at the inner nuclear membrane together with
      Lamin. Our data suggest that Char forms a scaffold that regulates nuclear
      architecture to constrain nuclei in tight columnar epithelial cells. The
      upregulation of Char during cellularisation and gastrulation reveals the
      existence of an as yet unknown developmental control of nuclear morphology and
      anchoring in embryonic epithelia.

PMID- 16421190
TI  - Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during
      mouse development.
AB  - Fibroblast growth factor receptor 1 (Fgfr1) plays pleiotropic roles during
      embryonic development, but the mechanisms by which this receptor signals in vivo
      have not previously been elucidated. Biochemical studies have implicated Fgf
      receptor-specific substrates (Frs2, Frs3) as the principal mediators of Fgfr1
      signal transduction to the MAPK and PI3K pathways. To determine the developmental
      requirements for Fgfr1-Frs signaling, we generated mice
      (Fgfr1(Delta)Frs/DeltaFrs) in which the Frs2/3-binding site on Fgfr1 is deleted.
      Fgfr1(Delta)Frs/DeltaFrs embryos die during late embryogenesis, and exhibit
      defects in neural tube closure and in the development of the tail bud and
      pharyngeal arches. However, the mutant receptor is able to drive Fgfr1 functions
      during gastrulation and somitogenesis, and drives normal MAPK responses to Fgf.
      These findings indicate that Fgfr1 uses distinct signal transduction mechanisms
      in different developmental contexts, and that some essential functions of this
      receptor are mediated by Frs-independent signaling.

PMID- 16421192
TI  - Direct regulation of egl-1 and of programmed cell death by the Hox protein MAB-5
      and by CEH-20, a C. elegans homolog of Pbx1.
AB  - Hox genes are crucial determinants of cell fates and of body morphology of
      animals; mutations affecting these genes result in abnormal patterns of
      programmed cell death. How Hox genes regulate programmed cell death is an
      important and poorly understood aspect of normal development. In the nematode C.
      elegans, the Hox gene mab-5 is required for the programmed cell deaths of two
      lineally related cells generated in the P11 and P12 lineages. We show here that
      in the P11 lineage, a complex between MAB-5 and the Pbx homolog CEH-20 directly
      regulates transcription of the BH3 domain gene egl-1 to initiate programmed cell
      death; in the P12 lineage, mab-5 and ceh-20 apparently act indirectly to initiate
      programmed cell death. Direct regulation of programmed cell death may be an
      evolutionarily ancient and conserved function of Hox genes.

PMID- 16421191
TI  - The C. elegans Myt1 ortholog is required for the proper timing of oocyte
      maturation.
AB  - Maturation promoting factor (MPF), a complex of cyclin-dependent kinase 1 and
      cyclin B, drives oocyte maturation in all animals. Mechanisms to block MPF
      activation in developing oocytes must exist to prevent precocious cell cycle
      progression prior to oocyte maturation and fertilization. This study sought to
      determine the developmental consequences of precociously activating MPF in
      oocytes prior to fertilization. Whereas depletion of Myt1 in Xenopus oocytes
      causes nuclear envelope breakdown in vitro, we found that depletion of the Myt1
      ortholog WEE-1.3 in C. elegans hermaphrodites causes precocious oocyte maturation
      in vivo. Although such oocytes are ovulated, they are fertilization incompetent.
      We have also observed novel phenotypes in these precociously maturing oocytes,
      such as chromosome coalescence, aberrant meiotic spindle organization, and the
      expression of a meiosis II post-fertilization marker. Furthermore, co-depletion
      studies of CDK-1 and WEE-1.3 demonstrate that WEE-1.3 is dispensable in the
      absence of CDK-1, suggesting that CDK-1 is a major target of WEE-1.3 in C.
      elegans oocytes.

PMID- 16421193
TI  - Regulation of somitogenesis by Ena/VASP proteins and FAK during Xenopus
      development.
AB  - The metameric organization of the vertebrate body plan is established during
      somitogenesis as somite pairs sequentially form along the anteroposterior axis.
      Coordinated regulation of cell shape, motility and adhesion are crucial for
      directing the morphological segmentation of somites. We show that members of the
      Ena/VASP family of actin regulatory proteins are required for somitogenesis in
      Xenopus. Xenopus Ena (Xena) localizes to the cell periphery in the presomitic
      mesoderm (PSM), and is enriched at intersomitic junctions and at myotendinous
      junctions in somites and the myotome, where it co-localizes with beta1-integrin,
      vinculin and FAK. Inhibition of Ena/VASP function with dominant-negative mutants
      results in abnormal somite formation that correlates with later defects in
      intermyotomal junctions. Neutralization of Ena/VASP activity disrupts cell
      rearrangements during somite rotation and leads to defects in the fibronectin
      (FN) matrix surrounding somites. Furthermore, inhibition of Ena/VASP function
      impairs FN matrix assembly, spreading of somitic cells on FN and
      autophosphorylation of FAK, suggesting a role for Ena/VASP proteins in the
      modulation of integrin-mediated processes. We also show that inhibition of FAK
      results in defects in somite formation, blocks FN matrix deposition and alters
      Xena localization. Together, these results provide evidence that Ena/VASP
      proteins and FAK are required for somite formation in Xenopus and support the
      idea that Ena/VASP and FAK function in a common pathway to regulate integrin
      dependent migration and adhesion during somitogenesis.

PMID- 16421194
TI  - XHas2 activity is required during somitogenesis and precursor cell migration in
      Xenopus development.
AB  - In vertebrates, hyaluronan biosynthesis is regulated by three transmembrane
      catalytic enzymes denoted Has1, Has2 and Has3. We have previously cloned the
      Xenopus orthologues of the corresponding genes and defined their spatiotemporal
      distribution during development. During mammalian embryogenesis, Has2 activity is
      known to be crucial, as its abrogation in mice leads to early embryonic
      lethality. Here, we show that, in Xenopus, morpholino-mediated loss-of-function
      of XHas2 alters somitogenesis by causing a disruption of the metameric somitic
      pattern and leads to a defective myogenesis. In the absence of XHas2, early
      myoblasts underwent apoptosis, failing to complete their muscle differentiation
      programme. XHas2 activity is also required for migration of hypaxial muscle cells
      and trunk neural crest cells (NCC). To approach the mechanism whereby loss of HA,
      following XHas2 knockdown, could influence somitogenesis and precursor cell
      migration, we cloned the orthologue of the primary HA signalling receptor CD44
      and addressed its function through an analogous knockdown approach. Loss of XCD44
      did not disturb somitogenesis, but strongly impaired hypaxial muscle precursor
      cell migration and the subsequent formation of the ventral body wall musculature.
      In contrast to XHas2, loss of function of XCD44 did not seem to be essential for
      trunk NCC migration, suggesting that the HA dependence of NCC movement was rather
      associated with an altered macromolecular composition of the ECM structuring the
      cells' migratory pathways. The presented results, extend our knowledge on Has2
      function and, for the first time, demonstrate a developmental role for CD44 in
      vertebrates. On the whole, these data underlie and confirm the emerging
      importance of cell-ECM interactions and modulation during embryonic development.

PMID- 16421195
TI  - Spatial resolution for feature binding is impaired in peripheral and amblyopic
      vision.
AB  - We measured spatial resolution for discriminating targets that differed from
      nearby distractors in either color or orientation or their conjunction. In the
      fovea of normal human observers, whenever both attributes are big enough to be
      individually visible, their conjunction is also visible. In the periphery, the
      two attributes may be visible, but their conjunction may be invisible. We found a
      similar impairment in resolving conjunctions for the fovea of deprived eyes of
      humans with abnormal visual development (amblyopia). These results are
      quantitatively explained by a model of primary visual cortex (V1) in which
      orientation and color maps are imperfectly co-registered topographically. Our
      results in persons with amblyopia indicate that the ability of the fovea to
      compensate for this poor co-registration is consolidated by visual experience
      during postnatal development.

PMID- 16421196
TI  - Differential mechanisms underlying the modulation of delayed-rectifier K+ channel
      in mouse neocortical neurons by nitric oxide.
AB  - The modulatory effects of nitric oxide (NO) on voltage-dependent K+ channels are
      intricate. In our present study, the augmentation and reduction of K+ currents by
      NO donor S-nitro-N-acetylpenicillamine (SNAP) and pure dissolved NO was observed
      in dissociated neurons from mice neocortex with both whole cell and cell-attached
      patch clamp. By using a specific electrochemical sensor, the critical
      concentrations of NO that increased or reduced the channel activities were
      accurately quantified. Low concentrations of SNAP (20 microM) or NO solution (0.1
      microM) enhanced whole cell delayed rectifier K+ -current (IK) and left the fast
      inactivating A current (IA) unchanged. However, high concentrations of SNAP (100
      microM) and NO (0.5 microM) reduced both IK and IA currents. In cell-attached
      experiments, a significant increase in channel open probability (NP0) was
      observed when using low concentrations of SNAP or NO. High concentrations of SNAP
      or NO dramatically decreased NP0. The increase in channel activities by low
      concentrations of SNAP was abolished in the presence of either inhibitors of
      soluble guaylate cyclase or inhibitors of cGMP-dependent protein kinase G,
      suggesting a link to the NO-cGMP signaling cascade. The reduction of channel
      activities by high concentrations of SNAP was reversed by the reducing agent
      dithiothreitol, implying a redox reaction mechanism. Thus both NO-cGMP signaling
      and a redox mechanism are involved in the modulation of IK channel activity for
      neuron excitability.

PMID- 16421197
TI  - Neuronal activity related to elapsed time in prefrontal cortex.
AB  - We studied prefrontal cortex activity during a saccade task. On each trial, one
      of three delay periods elapsed between the onset of a visual stimulus and its
      offset, which triggered a saccade. After stimulus offset, many neurons showed
      phasic increases in activity that depended on the duration of the preceding delay
      period. This delay-dependent activity varied only weakly with reaction time and
      instead appeared to reflect a more general aspect of elapsed time.

PMID- 16421201
TI  - Relationship between physiological response type (RA and SA) and vibrissal
      receptive field of neurons within the rat trigeminal ganglion.
AB  - Cells within the trigeminal ganglion (Vg) encode all the information necessary
      for the rat to differentiate tactile stimuli, yet it is the least-studied
      component in the rodent trigeminal somatosensory system. For example, extensive
      anatomical and electrophysiological investigations have shown clear somatotopic
      organization in the higher levels of this system, including VPM thalamus and SI
      cortex, yet whether this conserved schemata exists in the Vg is unknown. Moreover
      although there is recent interest in recording from vibrissae-responsive cells in
      the Vg, it is surprising to note that the locations of these cells have not even
      been clearly demarcated. To address this, we recorded extracellularly from 350
      sensory-responsive Vg neurons in 35 Long-Evans rats. First, we determined three
      dimensional locations of these cells and found a finer detail of somatotopy than
      previously reported. Cells innervating dorsal facial features, even within the
      whisker region, were more dorsal than midline and ventral features. We also show
      more cells with caudal than rostral whisker receptive fields (RF), similar to
      that found in VPM and SI. Next, for each vibrissal cell we determined its
      response type classified as either rapidly (RA) or slowly (SA) adapting. We
      examined the relationship between vibrissal RF and response type and demonstrate
      similar proportions of RA and SA cells responding to any whisker. These results
      suggest that if RA and SA cells encode distinct features of stimuli, as
      previously suggested, then at the basic physiological level each whisker has
      similar abilities to encode for such features.

PMID- 16421200
TI  - Differential roles for group 1 mGluR subtypes in induction and expression of
      chemically induced hippocampal long-term depression.
AB  - Although metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 are often
      found to have similar functions, there is considerable evidence that the two
      receptors also serve distinct functions in neurons. In hippocampal area CA1,
      mGluR5 has been most strongly implicated in long-term synaptic depression (LTD),
      whereas mGluR1 has been thought to have little or no role. Here we show that
      simultaneous pharmacological blockade of mGluR1 and mGluR5 is required to block
      induction of LTD by the group 1 mGluR agonist, (RS)-3,5-dihydroxyphenylglycine
      (DHPG). Blockade of mGluR1 or mGluR5 alone has no effect on LTD induction,
      suggesting that activation of either receptor can fully induce LTD. Consistent
      with this conclusion, mGluR1 and mGluR5 both contribute to activation of
      extracellular signal-regulated kinase (ERK), which has previously been shown to
      be required for LTD induction. In contrast, selective blockade of mGluR1, but not
      mGluR5, reduces the expression of LTD and the associated decreases in AMPA
      surface expression. LTD is also reduced in mGluR1 knockout mice confirming the
      involvement of mGluR1. This shows a novel role for mGluR1 in long-term synaptic
      plasticity in CA1 pyramidal neurons. In contrast to DHPG-induced LTD,
      synaptically induced LTD with paired-pulse low-frequency stimulation persists in
      the pharmacological blockade of group 1 mGluRs and in mGluR1 or mGluR5 knockout
      mice. This suggests different receptors and/or upstream mechanisms for chemically
      and synaptically induced LTD.

PMID- 16421199
TI  - Nicotinic and muscarinic reduction of unitary excitatory postsynaptic potentials
      in sensory cortex; dual intracellular recording in vitro.
AB  - We studied the cholinergic modulation of glutamatergic transmission between
      neighboring layer 5 regular-spiking pyramidal neurons in somatosensory cortical
      slices from young rats (P10-P26). Brief bath application of 5-10 microM
      carbachol, a nonspecific cholinergic agonist, decreased the amplitude of evoked
      unitary excitatory postsynaptic potentials (EPSPs). This effect was blocked by 1
      microM atropine, a muscarinic receptor antagonist. Nicotine (10 microM), in
      contrast to carbachol, reduced EPSPs in nominally magnesium-free solution but not
      in the presence of 1 mM Mg+2, indicating the involvement of NMDA receptors.
      Likewise, when the postsynaptic cell was depolarized under voltage clamp to allow
      NMDA receptor activation in the presence of 1 mM Mg+2, synaptic currents were
      reduced by nicotine. Nicotinic EPSP reduction was prevented by the NMDA receptor
      antagonist D-AP5 (50 microM) and by the nicotinic receptor antagonist
      mecamylamine (10 microM). Both carbachol and nicotine reduced short-term
      depression of EPSPs evoked by 10 Hz stimulation, indicating that EPSP reduction
      happens via reduction of presynaptic glutamate release. In the case of nicotine,
      several possible mechanisms for NMDAR-dependent EPSP reduction are discussed. As
      a result of NMDA receptor dependence, nicotinic EPSP reduction may serve to
      reduce the local spread of cortical excitation during heightened sensory
      activity.

PMID- 16421202
TI  - Convergence of Ca2+-desensitizing mechanisms activated by forskolin and
      phenylephrine pretreatment, but not 8-bromo-cGMP.
AB  - Contractile stimuli can sensitize myosin to Ca2+ by activating RhoA kinase (ROK)
      and PKC that inhibit myosin light chain phosphatase (MLCP) activity. Relaxant
      stimuli, acting through PKA and PKG (cyclic nucleotide-dependent protein
      kinases), and pretreatment with contractile agents such as phenylephrine (PE),
      can desensitize myosin to Ca2+. It is unknown precisely how these stimuli cause
      Ca2+ desensitization. To test the hypothesis that PKA, PKG, and PE pretreatment
      signaling systems converge to cause relaxation by inhibition of ROK in intact,
      isolated tissues, we examined the effects of forskolin (FSK; PKA activation), 8
      bromo-cGMP (8br-cGMP; PKG activation), and PE pretreatment on KCl-induced force
      maintenance in rabbit arteries, a response nearly completely dependent on ROK
      activation. PE pretreatment and agents activating PKA and PKG caused Ca2+
      desensitization by inhibiting KCl-induced tonic force and MLC phosphorylation
      without inhibiting intracellular [Ca2+]. At pCa 5 in beta-escin-permeabilized
      muscle, FSK and 8b-cGMP accelerated the relaxation rate when tissues were
      returned to pCa 9, suggesting that both agents can elevate MLCP activity.
      However, a component of the Ca2+ desensitization attributed to PKG activation in
      intact tissues appeared to involve a MLC phosphorylation-independent component.
      Inhibition of KCl-induced tonic force by the ROK inhibitor, Y-27632, and by PE
      pretreatment, were synergistically potentiated by 8b-cGMP, but not FSK. FSK and
      PE pretreatment, but not 8b-cGMP, inhibited the KCl-induced increase in site
      specific myosin phosphatase target protein-1 phosphorylation at Thr853. These
      data support the hypothesis that PKA and PE pretreatment converge on a common
      Ca2+-desensitization pathway, but that PKG can act by a mechanism different from
      that activated by PKA and PE pretreatment.

PMID- 16421203
TI  - Functional link between TNF biosynthesis and CaM-dependent activation of
      inducible nitric oxide synthase in RAW 264.7 macrophages.
AB  - Inflammatory responses stimulated by bacterial endotoxin LPS involve Ca2+
      mediated signaling, yet the cellular sensors that determine cell fate in response
      to LPS remain poorly understood. We report that exposure of RAW 264.7 macrophage
      like cells to LPS induces a rapid increase in CaM abundance, which is associated
      with the modulation of the inflammatory response. Increases in CaM abundance
      precede nuclear localization of key transcription factors (i.e., NF-kappaB p65
      subunit, phospho-c-Jun, Sp1) and subsequent increases in the proinflammatory
      cytokine TNF-alpha and inducible nitric oxide synthase (iNOS). Cellular apoptosis
      after LPS challenge is blocked upon inhibition of iNOS activity using the
      pharmacological inhibitor 1400W. LPS-mediated iNOS expression and apoptosis also
      were inhibited by siRNA-mediated silencing of TNF induction, indicating TNF
      induction both precedes and is necessary for subsequent regulation of iNOS
      expression. Increasing the level of cellular CaM by stable transfection results
      in reductions in LPS-induced expression of TNF and iNOS, along with reduced
      activation of their transcriptional regulators and concomitant protection against
      apoptosis. Thus the level of CaM available for Ca2+-dependent signaling
      regulation plays a key role in determining the expression of the proinflammatory
      and proapoptotic cascade during cellular activation by LPS. These results
      indicate a previously unrecognized central role for CaM in maintaining cellular
      homeostasis in response to LPS such that, under resting conditions, cellular
      concentrations of CaM are sufficient to inhibit the biosynthesis of
      proinflammatory mediators associated with macrophage activation. Although CaM and
      iNOS protein levels are coordinately increased as part of the oxidative burst,
      limiting cellular concentrations of CaM due to association with iNOS (and other
      high-affinity binders) commit the cell to an unchecked inflammatory cascade
      leading to apoptosis.

PMID- 16421205
TI  - PVD9902, a porcine vas deferens epithelial cell line that exhibits
      neurotransmitter-stimulated anion secretion and expresses numerous HCO3(-)
      transporters.
AB  - Epithelial ion transport disorders, including cystic fibrosis, adversely affect
      male reproductive function by nonobstructive mechanisms and by obstruction of the
      distal duct. Continuous cell lines that could be used to define ion transport
      mechanisms in this tissue are not readily available. In the present study,
      porcine vas deferens epithelial cells were isolated by standard techniques, and
      the cells spontaneously immortalized to form a porcine vas deferens epithelial
      cell line that we have titled PVD9902. Cells were maintained in continuous
      culture for >4 yr and 200 passages in a typical growth medium. Frozen stocks were
      generated, and thawed cells exhibited growth characteristics indistinguishable
      from their nonfrozen counterparts. Molecular and immunocytochemical studies
      confirmed the origin and epithelial nature of these cells. When seeded on
      permeable supports, PVD9902 cells grew as electrically tight (>6,000 ohms x cm2),
      confluent monolayers that responded to forskolin with an increase in short
      circuit current (I(sc); 8 +/- 1 microA/cm2) that required Cl-, HCO3(-), and Na+,
      and was partially sensitive to bumetanide. mRNA was expressed for a number of
      anion transporters, including CFTR, electrogenic Na+-HCO3(-) cotransporter 1b
      (NBCe1b), downregulated in adenoma, pendrin, and Cl-/formate exchanger. Both
      forskolin and isoproterenol caused an increase in cellular cAMP levels. In
      addition, PVD9902 cell monolayers responded to physiological (i.e., adenosine,
      norepinephrine) and pharmacological [i.e., 5'-(N-ethylcarboxamido)adenosine,
      isoproterenol] agonists with increases in I(sc). Unlike their freshly isolated
      counterparts, however, PVD9902 cells did not respond to glucocorticoid exposure
      with an increase in amiloride-sensitive I(sc). RT-PCR analysis revealed the
      presence of both glucocorticoid and mineralocorticoid receptor mRNA as well as
      mRNA for the alpha- and gamma-subunits of the epithelia Na+ channels (alpha- and
      gamma-ENaC), but not beta-ENaC. Nonetheless, PVD9902 cells recapitulated most
      observations in freshly isolated cells and thus represent a powerful new tool to
      characterize mechanisms that contribute to male reproductive function.

PMID- 16421204
TI  - Protein kinase D protects against oxidative stress-induced intestinal epithelial
      cell injury via Rho/ROK/PKC-delta pathway activation.
AB  - Protein kinase D (PKD) is a novel protein serine kinase that has recently been
      implicated in diverse cellular functions, including apoptosis and cell
      proliferation. The purpose of our present study was 1) to define the activation
      of PKD in intestinal epithelial cells treated with H2O2, an agent that induces
      oxidative stress, and 2) to delineate the upstream signaling mechanisms mediating
      the activation of PKD. We found that the activation of PKD is induced by H2O2 in
      both a dose- and time-dependent fashion. PKD phosphorylation was attenuated by
      rottlerin, a selective PKC-delta inhibitor, and by small interfering RNA (siRNA)
      directed against PKC-delta, suggesting the regulation of PKD activity by upstream
      PKC-delta. Activation of PKD was also blocked by a Rho kinase (ROK)-specific
      inhibitor, Y-27632, as well as by C3, a Rho protein inhibitor, demonstrating that
      the Rho/ROK pathway also mediates PKD activity in intestinal cells. In addition,
      H2O2-induced PKC-delta phosphorylation was inhibited by C3 treatment, further
      suggesting that PKC-delta is downstream of Rho/ROK. Interestingly, H2O2-induced
      intestinal cell apoptosis was enhanced by PKD siRNA. Together, these results
      clearly demonstrate that oxidative stress induces PKD activation in intestinal
      epithelial cells and that this activation is regulated by upstream PKC-delta and
      Rho/ROK pathways. Importantly, our findings suggest that PKD activation protects
      intestinal epithelial cells from oxidative stress-induced apoptosis. These
      findings have potential clinical implications for intestinal injury associated
      with oxidative stress (e.g., necrotizing enterocolitis in infants).

PMID- 16421206
TI  - Implication of CO inactivation on myoglobin function.
AB  - Myoglobin (Mb) has a purported role in facilitating O2 diffusion in tissue,
      especially as cellular PO2 drops or the respiration demand increases. Inhibiting
      Mb with CO under conditions that accentuate the facilitated diffusion role should
      then elicit a significant physiological response. In one set of experiments, the
      perfused myocardium received buffer with decreasing PO2 (225, 129, and 64 mmHg).
      Intracellular PO2 declined, as reflected in the 1H NMR Val E11 signal of MbO2
      (67%, 32%, and 18%). The addition of 6% CO further reduced the available MbO2
      (11%, 9%, and 7%), as evidenced by the decline of the MbO2 Val E11 signal
      intensity at -2.76 ppm. In a second set of experiments, electrical stimulation
      increased the heart rate (300, 450, and 540 beats/min) and correspondingly the O2
      consumption rate (MVO2). Intracellular PO2 also declined, as reflected in the
      slight drop in the MbO2 signal (100%, 96%, and 82%). MVO2 increased (100%, 114%,
      165%). The addition of 3% CO in the stimulated hearts further decreased the
      available MbO2 (46%, 44%, and 29%). In all cases, CO inactivation of Mb does not
      induce any change in the respiration rate, contractile function, and high-energy
      phosphate levels. Moreover, the MbCO/MbO2 partition coefficient shifts
      dramatically from its in vitro value during hypoxia and increased work. The
      observation suggests a modulation of an intracellular O2 gradient. Overall, the
      experimental observations provide no evidence of a facilitated diffusion role for
      Mb in perfused myocardium and implicate a physiologically responsive
      intracellular O2 gradient.

PMID- 16421207
TI  - Alpha7beta1-integrin regulates mechanotransduction and prevents skeletal muscle
      injury.
AB  - Alpha7beta1-integrin links laminin in the extracellular matrix with the cell
      cytoskeleton and therein mediates transduction of mechanical forces into chemical
      signals. Muscle contraction and stretching ex vivo result in activation of
      intracellular signaling molecules that are integral to postexercise injury
      responses. Because alpha7beta1-integrin stabilizes muscle and provides
      communication between the matrix and cytoskeleton, the role of this integrin in
      exercise-induced cell signaling and skeletal muscle damage was assessed in wild
      type and transgenic mice overexpressing the alpha7BX2 chain. We report here that
      increasing alpha7beta1-integrin inhibits phosphorylation of molecules associated
      with muscle damage, including the mitogen-activated protein kinases (JNK, p38,
      and ERK), following downhill running. Likewise, activation of molecules
      associated with hypertrophy (AKT, mTOR, and p70(S6k)) was diminished in mice
      overexpressing integrin. While exercise resulted in Evans blue dye-positive
      fibers, an index of muscle damage, increased integrin protected mice from injury.
      Moreover, exercise leads to an increase in alpha7beta1 protein. These experiments
      provide the first evidence that alpha7beta1-integrin is a negative regulator of
      mechanotransduction in vivo and provides resistance to exercise-induced muscle
      damage.

PMID- 16421208
TI  - Disulfonic stilbene permeation and block of the anion channel from the
      sarcoplasmic reticulum of rabbit skeletal muscle.
AB  - Block of a sarcoplasmic reticulum anion channel (SCl channel) by disulfonic
      stilbene derivatives [DIDS, dibenzamidostilbene-2,2'-disulfonic acid (DBDS), and
      4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS)] was investigated in planar
      bilayers using SO4(2-) as the conducting ion. All molecules caused reversible
      voltage-dependent channel block when applied to either side of the membrane. DIDS
      also produced nonreversible channel block from both sides within 1-3 min.
      Reversible inhibition was associated with a decrease in channel open probability
      and mean open duration but not with any change in channel conductance. The half
      inhibitory concentration for cis- and trans-inhibition had voltage dependencies
      with minima of 190 nM and 33 microM for DBDS and 3.4 and 55 microM for DNDS. Our
      data supports a permeant blocker mechanism, in which stilbenes block SCl channels
      by lodging in the permeation pathway, where they may dissociate to either side of
      the membrane and thus permeate the channel. The stilbenes acted as open channel
      blockers where the binding of a single molecule occludes the channel. DBDS and
      DNDS, from opposite sides of the membrane, competed for common sites on the
      channel. Dissociation rates exhibited biphasic voltage dependence, indicative of
      two dissociation processes associated with ion movement in opposite directions
      within the trans-membrane electric field. The kinetics of DNDS and DBDS
      inhibition predict that there are two stilbene sites in the channel that are
      separated by 14-24 A and that the pore constriction is approximately 10 A in
      diameter.

PMID- 16421209
TI  - Store-operated Ca2+ entry modulates sarcoplasmic reticulum Ca2+ loading in
      neonatal rabbit cardiac ventricular myocytes.
AB  - Store-operated Ca2+ entry (SOCE), which is Ca2+ entry triggered by the depletion
      of intracellular Ca2+ stores, has been observed in many cell types, but only
      recently has it been suggested to occur in cardiomyocytes. In the present study,
      we have demonstrated SOCE-dependent sarcoplasmic reticulum (SR) Ca2+ loading
      (load(SR)) that was not altered by inhibition of L-type Ca2+ channels, reverse
      mode Na+/Ca2+ exchange (NCX), or nonselective cation channels. In contrast,
      lowering the extracellular [Ca2+] to 0 mM or adding either 0.5 mM Zn2+ or the
      putative store-operated channel (SOC) inhibitor SKF-96365 (100 microM) inhibited
      load(SR) at rest. Interestingly, inhibition of forward mode NCX with 30 microM KB
      R7943 stimulated SOCE significantly and resulted in enhanced load(SR). In
      addition, manipulation of the extracellular and intracellular Na+ concentrations
      further demonstrated the modulatory role of NCX in SOCE-mediated SR Ca2+ loading.
      Although there is little knowledge of SOCE in cardiomyocytes, the present results
      suggest that this mechanism, together with NCX, may play an important role in SR
      Ca2+ homeostasis. The data reported herein also imply the presence of
      microdomains unique to the neonatal cardiomyocyte. These findings may be of
      particular importance during open heart surgery in neonates, in which
      uncontrolled SOCE could lead to SR Ca2+ overload and arrhythmogenesis.

PMID- 16421210
TI  - Pathobiology of sepsis: are we still asking the same questions?

PMID- 16421211
TI  - Multicellularity and the functional interdependence of motility and molecular
      transport.
AB  - Benefits, costs, and requirements accompany the transition from motile totipotent
      unicellular organisms to multicellular organisms having cells specialized into
      reproductive (germ) and vegetative (sterile soma) functions such as motility. In
      flagellated colonial organisms such as the volvocalean green algae, organized
      beating by the somatic cells' flagella yields propulsion important in phototaxis
      and chemotaxis. It has not been generally appreciated that for the larger
      colonies flagellar stirring of boundary layers and remote transport are
      fundamental for maintaining a sufficient rate of metabolite turnover, one not
      attainable by diffusive transport alone. Here, we describe experiments that
      quantify the role of advective dynamics in enhancing productivity in germ soma
      differentiated colonies. First, experiments with suspended deflagellated colonies
      of Volvox carteri show that forced advection improves productivity. Second,
      particle imaging velocimetry of fluid motion around colonies immobilized by
      micropipette aspiration reveals flow fields with very large characteristic
      velocities U extending to length scales exceeding the colony radius R. For a
      typical metabolite diffusion constant D, the associated Peclet number Pe = 2UR/D
      >> 1, indicative of the dominance of advection over diffusion, with striking
      augmentation at the cell division stage. Near the colony surface, flows generated
      by flagella can be chaotic, exhibiting mixing due to stretching and folding.
      These results imply that hydrodynamic transport external to colonies provides a
      crucial boundary condition, a source for supplying internal diffusional dynamics.

PMID- 16421212
TI  - Acetylcholine causes an increase of intracellular calcium in human sperm.
AB  - Sperm nicotinic acetylcholine receptors (nAChRs) can influence motility and the
      initiation of acrosome reaction (AR). We report that AR initiation by
      acetylcholine (ACh) in capacitated human sperm requires both Na+ and Ca2+ in the
      external medium. Pre-incubation with 50 microM 3-quinuclidinyl benzilate (QNB) or
      50 nM strychnine failed to inhibit the ACh-initiated AR, demonstrating that
      muscarinic AChRs and nAChRs containing alpha9 subunits do not mediate this event.
      Choline (2.5, 5 and 10 mM), a highly specific but low potency agonist of the
      alpha7 nAChR initiated AR, with its effect blocked by the nAChR antagonist
      methyllycaconitine (MLA). ACh (50-400 microM) stimulated a small transient rise
      in the intracellular Ca2+ in sperm populations loaded with FURA-2, with 200
      microM ACh being maximal (146 nM +/- 23 SEM). The nAChR antagonists, alpha
      bungarotoxin (alpha-BTX) and MLA, reduced the ACh-initiated Ca2+ rise by 75 and
      78%, respectively, demonstrating the majority of the rise is mediated through
      nAChRs containing alpha7 or alpha9 subunits. Single cell imaging studies using
      FLUO-3 resolved two patterns of ACh-stimulated Ca2+ increase in the sperm head:
      94% of responding sperm displayed a rise (59.6% +/- 5.7 SEM increase from resting
      fluorescence intensity), returning to resting levels over a period of 2-3 min.
      The remaining sperm (6%) displayed a sharp spike of Ca2+ ( approximately 1 min;
      86% +/- 4.3 SEM change in fluorescence intensity), followed by abrupt loss of
      fluorescence, a pattern suggestive of AR. A Ca2+ influx in the sperm midpiece
      appeared to accompany the Ca2+ influx seen in the head. These observations
      confirm an ionotropic role for nAChRs in sperm function.

PMID- 16421213
TI  - Mitochondrial DNA content and 4977 bp deletion in unfertilized oocytes.
AB  - Previous studies analysing the incidences of mitochondrial DNA (mtDNA) deletions
      and mtDNA content in unfertilized oocytes in relation to donors' age have been
      controversial. The objective of the study was to compare these two parameters in
      unfertilized oocytes and relate them to the donors' age. Fifty-two women donated
      155 unfertilized metaphase II (MII) oocytes. The incidence of 4977 bp deletion
      was 34.6%, and the mtDNA copy number was 598 350 +/- 265 862. Women >or=35 years
      of age had a significantly higher incidence of 4977 bp deletion, lower mtDNA copy
      number, higher FSH level and poorer ovarian response when compared with younger
      women. The mtDNA copy number was negatively correlated with the donor's age. The
      higher incidence of mtDNA deletion and lower mtDNA copy number in older women
      suggested that these two parameters may reflect ovarian ageing.

PMID- 16421214
TI  - Prostanoid receptors in human uterine myocytes: the effect of reproductive state
      and stretch.
AB  - In the human, prostanoids are known to be important mediators of uterine
      relaxation and contraction during pregnancy and parturition. We have previously
      shown that stretch of uterine smooth muscle cells increased prostaglandin H
      synthase 2 (PGHS-2) mRNA expression, PGHS-2 peptide synthesis and activity,
      however, the net effect on uterine contractility of this increase in
      prostaglandin synthesis would be determined by the expression of the different
      prostanoid receptors. Therefore, the aims of this study were to establish the
      expression of prostanoid receptor mRNA in uterine myocytes obtained from women in
      different reproductive states and to test the hypothesis that stretch of uterine
      myocytes alters prostanoid receptor mRNA expression to promote uterine
      contractility. Myocytes were isolated from women undergoing hysterectomy (NP) and
      pregnant women undergoing LSCS either before (NL) or after the onset of labour
      (L) and were subjected to 11% stretch for 1 h (n = 6 in all cases). Copy numbers
      of the individual receptors varied widely with reproductive state but followed
      the pattern: FP > IP = DP = EP-4 > TP = EP-3 = EP-2 > EP-1. FP mRNA expression
      was significantly lower in the NL group compared to the NP group and EP-3, EP-4
      and TP mRNA expression was significantly lower in both NL and L groups compared
      to NP group levels. The level of mRNA expression of EP-1, EP-2, DP and IP did not
      differ between NP, NL and L groups. Stretch of cells derived from the NP group
      resulted in a significant decrease in EP-4 mRNA expression alone and of the NL
      group a significant decrease in EP-2 mRNA expression alone. Stretch had no effect
      on cells derived from the L group. These data show that pregnancy is associated
      with a significant reduction in 3 of 4 pro-contraction associated prostanoid
      receptor mRNA expression and 1 of 4 pro-relaxant. Stretch elicited no consistent
      change in prostanoid receptor mRNA expression.

PMID- 16421215
TI  - Characterization of potassium channels involved in volume regulation of human
      spermatozoa.
AB  - Fertility depends in part on the ability of the spermatozoon to respond to
      osmotic challenges by regulating its volume, which may rely on the movement of
      K+. These experiments were designed to characterize the K+ channels possibly
      involved in volume regulation of human ejaculated spermatozoa by simultaneously
      exposing them to a physiological hypo-osmotic challenge and a wide range of K+
      channel inhibitors. Regulation of cellular volume, as measured by flow cytometry,
      was inhibited when spermatozoa were exposed to quinine (QUI; 0.3 mM), 4
      aminopyridine (4AP; 4 mM) and clofilium (CLO; 10 microM) which suggests the
      involvement of voltage-gated K+ channels Kv1.4, Kv1.5 and Kv1.7, acid-sensitive
      channel TASK2 and the beta-subunit minK (IsK) in regulatory volume decrease
      (RVD). QUI and 4AP and, to some extent, CLO also induced hyper activation-like
      motility. A sensitivity of RVD to pH could not be demonstrated in spermatozoa to
      support the involvement of TASK2 channels. Western blotting indicated the
      presence of Kv1.5, TASK2, TASK3 and minK channel proteins, but not Kv1.4.
      Furthermore, Kv1.5, minK and TASK2 were localized to various regions of the
      spermatozoa. Although Kv1.4, Kv1.7, TASK2 and TASK3 channels may have important
      roles in human spermatozoa, Kv1.5 and minK appear to be the most likely
      candidates for human sperm RVD, serving as targets for non-hormonal
      contraception.

PMID- 16421216
TI  - Expression of SLC26A3, CFTR and NHE3 in the human male reproductive tract: role
      in male subfertility caused by congenital chloride diarrhoea.
AB  - Congenital chloride diarrhoea (CLD) is a rare inherited disease caused by
      mutations in the solute carrier family 26 member 3 (SLC26A3) gene. Disruption of
      intestinal Cl(-)/HCO(3)(-) exchange causes watery Cl(-) rich diarrhoea from
      birth, and recently male subfertility was observed as a novel manifestation.
      Expression of SLC26A3, together with interacting proteins cystic fibrosis
      transmembrane conductance regulator (CFTR) and Na(+)/H(+) exchanger 3 (NHE3), was
      studied using immunohistochemistry in the testis (n = 2) and efferent ducts (ED)
      (n = 1) of patients with CLD (V317del genotype) and in the testis and epididymis
      (n = 11), seminal vesicle (n = 9) and prostate (n = 4) of the controls. SLC26A3
      was immunolocalized in the head of the elongating spermatids (stages III-VI) and
      CFTR in the elongating spermatids (stages III and IV) and pachytene (stages III
      V) and diplotene spermatocytes. In the non-ciliated cells of the ED, apical
      expression of all three proteins was observed, but only SLC26A3 and CFTR were
      detected on the luminal border of the apical mitochondria-rich cells (AMRC) of
      the ductus epididymis and in the epithelium of the seminal vesicle. Only CFTR was
      present in the epithelium of the prostatic duct. In the patient with CLD, the
      expression of both SLC26A3 and CFTR was absent in the ED, but testicular
      expression was identical to that of the controls. These results suggest a primary
      role for SLC26A3 in male reproduction. Tissue-specific co-expression with CFTR
      and NHE3 supports diverse functions of SLC26A3 and may have an impact on
      pathophysiology of male subfertility both in CLD and in cystic fibrosis (CF), as
      well as spermatoceles.

PMID- 16421217
TI  - Full karyotyping, rapid aneuploidy diagnosis or both when invasive prenatal
      testing is performed for diagnosis of thalassaemia?
AB  - A retrospective study was performed to compare the detection rate of chromosomal
      abnormalities by different approaches of full karyotyping, rapid aneuploidy
      diagnosis (RAD) or both when invasive prenatal testing is performed for diagnosis
      of thalassaemia. The karyotype results of 1120 prenatal samples obtained from
      thalassaemia couples from January 1985 to December 2002 in a referral centre for
      prenatal diagnosis were studied. The detection rate of chromosomal abnormalities
      by four different approaches were compared: (i) karyotyping for all samples; (ii)
      RAD (21,18,13,X,Y) for all samples; (iii) RAD for all samples + karyotyping for
      cases with ultrasound abnormalities; and (iv) RAD (21,18,13) for all + RAD (X,Y)
      for cases with ultrasound abnormalities consistent with Turner syndrome +
      karyotyping for cases with ultrasound abnormalities. Normal karyotypes were found
      in 1103 samples (98.5%). There were 17 cases (1.5%) of chromosomal abnormalities:
      four cases (0.36%) were clinically significant, eight cases (0.7%) were of
      borderline clinical significance and five cases (0.44%) were not confirmed by
      subsequent prenatal or postnatal tests. The incidences of autosomal (7/1120 =
      0.63%) and sex chromosomal (5/1120 = 0.45%) abnormalities were not higher than
      those (0.41 and 0.22%, respectively) from newborn surveys (Hook and Hamerton,
      1977) (P = 0.398 and 0.216, respectively). Approach 1 would detect all 17
      chromosomal abnormalities. Approach 2 would detect three of four clinically
      significant chromosomal abnormalities but not detect six of eight chromosomal
      abnormalities of borderline clinical significance and three of five chromosomal
      abnormalities not confirmed by subsequent prenatal or postnatal tests. Approach
      3, in addition, would be able to detect all four clinically significant
      chromosomal abnormalities. Approach 4 would detect all four clinically
      significant chromosomal abnormalities but would not detect seven of eight
      chromosomal abnormalities of borderline clinical significance and four of five
      chromosomal abnormalities not confirmed by subsequent prenatal or postnatal
      tests. RAD (21,18,13) for all + RAD (X,Y) for cases with ultrasound abnormalities
      consistent with Turner syndrome + karyotyping for cases with ultrasound
      abnormalities seemed to be the best approach for the detection of chromosomal
      abnormalities when invasive prenatal testing is performed for diagnosis of
      thalassaemia.

PMID- 16421218
TI  - Oct-4 expression in human endometrium.
AB  - The transcription factor Oct-4 is crucial for the maintenance of cell
      pluripotency and is known to be expressed in embryonic stem cells, germ cells and
      whole embryos at various stages of development. Oct-4 regulates cell fate in a
      dose-dependent manner and plays a key role in germ-cell tumours. In the past,
      several stem-cell markers have been detected, and their role in the pathogenesis
      of diseases has been discussed frequently. Thus, we investigated the expression
      of Oct-4 comparing its occurrence in endometrium of healthy and diseased women
      using immunohistochemistry (IHC) and RT-PCR. IHC demonstrated Oct-4 expression in
      25 of 60 sections (42%), respectively in 11 out of 25 patients (44%). Oct-4 mRNA
      was detected by RT-PCR in all tested samples (9 of 9) of endometrium, although
      the levels of expression varied. To our knowledge, this is the first study
      demonstrating Oct-4 expression in human endometrium.

PMID- 16421219
TI  - A repository of ENU mutant mouse lines and their potential for male fertility
      research.
AB  - Many of the proteins and their encoding genes involved in spermatogenesis are
      unknown, making the specific diagnosis and treatment of infertility in males
      difficult and highlighting the importance of identifying new genes that are
      involved in spermatogenesis. Through genome-wide chemical mutagenesis using N
      ethyl-N-nitrosourea (ENU) and a three-generation breeding scheme to isolate
      recessive mutations, we have identified mouse lines with a range of abnormalities
      relevant to human male fertility. Abnormal phenotypes included
      hypospermatogenesis, Sertoli cell-only (SCO) seminiferous tubules, germ-cell
      arrest and abnormal spermiogenesis and were accompanied, in some, with abnormal
      serum levels of reproductive hormones. In total, from 65 mouse lines, 14 showed a
      reproductive phenotype consistent with a recessive mutation. This study shows
      that it is feasible to use ENU mutagenesis as an effective and rapid means of
      generating mouse models relevant to furthering our understanding of human male
      infertility. Spermatozoa and genomic DNA from all mouse lines, including those
      with abnormal reproductive tract parameters, have been cryopreserved for the
      regeneration of lines as required. This repository will form a valuable resource
      for the identification and analysis of key regulators of multiple aspects of male
      fertility.

PMID- 16421220
TI  - IDO expression on decidual and peripheral blood dendritic cells and
      monocytes/macrophages after treatment with CTLA-4 or interferon-gamma increase in
      normal pregnancy but decrease in spontaneous abortion.
AB  - Recent data demonstrated that CD4+CD25+ regulatory T (Treg) cells and an enzyme
      called indoleamine 2,3-dioxygenase (IDO) mediate maternal tolerance to the fetus.
      Interestingly, Treg cells express the CTLA-4 molecule on their surface, and B7
      (CD80/86) ligation by CTLA-4 enhanced IDO activity of dendritic cells (DCs) and
      monocytes by the induction of interferon gamma (IFN-gamma) production. In this
      study, we studied the IDO expression on peripheral blood monocytes and decidual
      monocytes or DCs after treatment with CTLA-4/Fc fusion protein or IFN-gamma using
      flow cytometry. IDO expressions on both peripheral blood DC and decidual DC and
      monocytes were up-regulated during normal pregnancy. On the other hand, both IDO
      expression on DC and monocytes after IFN-gamma treatment or CTLA-4 treatment were
      decreased in spontaneous abortion cases. The expression of CD86 on peripheral
      blood and decidual monocytes and DC in spontaneous abortion cases was lower
      compared with those in normal pregnancy subjects. Also, IFN-gamma production by
      decidual and peripheral blood mononuclear cells after CTLA-4/Fc treatment in
      spontaneous abortion cases was significantly lower than those in normal pregnancy
      subjects. These data suggest that CTLA-4 on Treg cells up-regulates IDO
      expression on decidual and peripheral blood DC and monocytes by the induction of
      IFN-gamma production.

PMID- 16421224
TI  - Heat shock-induced protection of renal proximal tubular epithelial cells from
      cold storage and rewarming injury.
AB  - Cold storage and reperfusion injury to transplanted kidneys contributes to
      increased incidence of delayed graft function and may have a negative impact on
      graft survival. This study examined the mechanisms by which previous heat shock
      protects against cell death in an in vitro model of kidney storage. Cold storage
      is mimicked by incubating human renal proximal tubular epithelial (HK-2) cells in
      University of Wisconsin solution at 4 degrees C with and without subsequent
      rewarming. Heat shock was induced by incubation of cells at 42 degrees C for 1 h.
      Altered protein expression was measured by Western blot, and cell viability and
      apoptosis were measured by propidium iodide DNA staining using flow cytometry.
      The specific role of heat-shock protein 70 (HSP-70) was determined both by siRNA
      knockdown and by stable overexpression approaches. Cold storage and rewarming
      induced cell death was associated with decreased expression of HSP-70, HSP-90,
      HSP-27, and Bcl-2. Previous heat shock significantly reduced HK-2 cell death
      after cold storage and rewarming and was associated with the maintenance of HSP
      70, HSP-27, and Bcl-2 protein levels. Blocking heat stress-induced HSP-70 with
      siRNA did not significantly block the protective effect of heat stress against
      cold storage and rewarming cell death; however, overexpression of HSP-70
      protected HK-2 cells from this stress. It is concluded that previous heat shock
      protects HK-2 cells from cold storage and rewarming injury. siRNA inhibition of
      HSP-70 induction did not block the protective effect of heat shock, indicating
      that HSP-70 is not essential to the heat stress-induced protective effect
      reported in this study.

PMID- 16421225
TI  - Acute blood pressure effects and chronic hypotensive action of calcimimetics in
      uremic rats.
AB  - A previous study in subtotally nephrectomized (SNX) rats suggested beneficial
      effects of the calcimimetic R-568 beyond the control of mineral metabolism. This
      study analyzed potential blood pressure (BP)-lowering effects of R-568. Male
      Sprague-Dawley rats received two-stage subtotal nephrectomy or sham operation.
      Telemetry devices were inserted into the abdominal aorta, and BP was measured
      every 5 min. R-568 (20 mg/kg per d) or solvent was infused for 4 wk followed by
      once-daily subcutaneous injections for 2 wk. Total body sodium was measured by
      neutron activation analysis. The uremia-induced increase of mean arterial
      pressure from baseline to day 42 in SNX solvent rats (103+/-5 to 128+/-14 mmHg,
      P=0.006) was attenuated by R-568 (104+/-5 to 111+/-8 mmHg; P<0.0001 for
      difference of slopes). The circadian rhythm was abrogated in SNX rats and not
      restored by R-568. In sham-operated rats, R-568 had only a minor transient
      antihypertensive effect. R-568 injection induced a transient rise of mean
      arterial pressure by 23+/-4 and 26+/-10 mmHg in sham and SNX rats but only by 9+/
      3 and 10+/-5 mmHg in solvent-treated rats (P<0.01 versus baseline and solvent
      versus R-568). Plasma angiotensin-converting enzyme activity and aldosterone
      levels were similar; food intake and physical activity did not differ throughout
      the study. In healthy rats, total body sodium was higher after 14 d of R-568
      compared with solvent infusion (37.1+/-4 versus 32.5+/-1.4 mmol/kg; P=0.01). The
      calcimimetic R-568 causes an initial BP increase in sham-operated and uremic
      rats, which in uremic rats is followed by a marked and sustained antihypertensive
      effect.

PMID- 16421227
TI  - Acid-base status determines the renal expression of Ca2+ and Mg2+ transport
      proteins.
AB  - Chronic metabolic acidosis results in renal Ca2+ and Mg2+ wasting, whereas
      chronic metabolic alkalosis is known to exert the reverse effects. It was
      hypothesized that these adaptations are mediated at least in part by the renal
      Ca2+ and Mg2+ transport proteins. The aim of this study, therefore, was to
      determine the effect of systemic acid-base status on renal expression of the
      epithelial Ca2+ channel TRPV5, the Ca2+-binding protein calbindin-D28K, and the
      epithelial Mg2+ channel TRPM6 in relation to Ca2+ and Mg2+ excretion. Chronic
      metabolic acidosis that was induced by NH4Cl loading or administration of the
      carbonic anhydrase inhibitor acetazolamide for 6 d enhanced calciuresis
      accompanied by decreased renal TRPV5 and calbindin-D28K mRNA and protein
      abundance in wild-type mice. In contrast, metabolic acidosis did not affect Ca2+
      excretion in TRPV5 knockout (TRPV5-/-) mice, in which active Ca2+ reabsorption is
      effectively abolished. This demonstrates that downregulation of renal Ca2+
      transport proteins is responsible for the hypercalciuria. Conversely, chronic
      metabolic alkalosis that was induced by NaHCO3 administration for 6 d increased
      the expression of Ca2+ transport proteins accompanied by diminished urine Ca2+
      excretion in wild-type mice. However, this Ca2+-sparing action persisted in TRPV5
      /- mice, suggesting that additional mechanisms apart from upregulation of active
      Ca2+ transport contribute to the hypocalciuria. Furthermore, chronic metabolic
      acidosis decreased renal TRPM6 expression, increased Mg2+ excretion, and
      decreased serum Mg2+ concentration, whereas chronic metabolic alkalosis resulted
      in the exact opposite effects. In conclusion, these data suggest that regulation
      of Ca2+ and Mg2+ transport proteins contributes importantly to the effects of
      acid-base status on renal divalent handling.

PMID- 16421228
TI  - Adverse perinatal outcome and later kidney biopsy in the mother.
AB  - Strong associations of adverse perinatal outcomes have been identified with later
      cardiovascular disease in the mother. Few studies have addressed associations
      with kidney disease. This study investigated whether perinatal outcomes are
      associated with later clinical kidney disease as diagnosed by kidney biopsy. The
      Medical Birth Registry of Norway contains data on all childbirths in Norway since
      1967. The Norwegian Kidney Biopsy Registry contains data on all kidney biopsies
      in Norway since 1988. All women with a first singleton delivery from 1967 to 1998
      were included. Pregnancy-related predictors of later kidney biopsy were analyzed
      by Cox regression analyses. A total of 756,420 women were included, and after a
      mean period of 15.9+/-9.4 yr, 588 had a kidney biopsy. Compared with women
      without preeclampsia and with offspring with birth weight of >or=2.5 kg, women
      with no preeclampsia and with offspring with birth weight of 1.5 to 2.5 kg had a
      relative risk (RR) for a later kidney biopsy of 1.7, women with no preeclampsia
      and with offspring with birth weight of <1.5 kg had an RR of 2.9, women with
      preeclampsia and with offspring with a birth weight of >or=2.5 kg had an RR of
      2.5, women with preeclampsia and with offspring with a birth weight of 1.5 to 2.5
      kg had an RR of 4.5, and women with preeclampsia and with offspring with a birth
      weight of <1.5 kg had an RR of 17. Similar results were found in adjusted
      analyses and after exclusion of women with diabetes, kidney disease, or rheumatic
      disease before pregnancy. The same risk patterns applied to any of the specific
      categories of kidney disease as well as specific kidney diseases investigated.
      Women who have preeclampsia and give birth to offspring with low birth weight and
      short gestation have a substantially increased risk for having a later kidney
      biopsy.

PMID- 16421229
TI  - Functional polymorphisms in the vascular endothelial growth factor gene are
      associated with development of end-stage renal disease in males.
AB  - This study elucidates the genetic role of vascular endothelial growth factor
      (VEGF) as a predisposing factor for progression of chronic kidney disease. Single
      nucleotide polymorphisms were genotyped and haplotype structures were determined
      in the 3' untranslated region (UTR) of VEGF gene, and the distribution of each
      haplotype in male patients with ESRD (n=101) and healthy male control subjects
      (n=189) was examined. The 936C/T and 1451C/T polymorphisms in the 3' UTR were in
      nearly absolute linkage disequilibrium, and haplotype analysis demonstrated that
      they were the primary responsible single-nucleotide polymorphisms. The
      distribution of the 936CC-1451CC genotype was significantly more frequent among
      patients with ESRD than among the age-matched healthy control subjects. In
      addition to case-control association study, the 936CC-1451CC genotype was also
      associated with significantly higher plasma VEGF levels in healthy individuals,
      but a significant association was found only in males, not in females. We also
      examined the effect of the 936C-1451C haplotype on mRNA stability. Consistent
      with the results of plasma VEGF levels, mRNA carrying 936C-1451C haplotype showed
      higher stability. The 936CC-1451CC genotype in the 3' UTR showed not only
      susceptibility for ESRD but also higher plasma VEGF levels and mRNA stability,
      indicating the contribution of VEGF to chronic kidney disease progression,
      especially in males.

PMID- 16421230
TI  - Innate immunity at the mucosal surface: role of toll-like receptor 3 and toll
      like receptor 9 in cervical epithelial cell responses to microbial pathogens.
AB  - Toll-like receptors (TLRs) are a family of pattern recognition receptors that
      recognize distinct molecular patterns shared by a broad range of pathogens,
      including nucleic acids. TLR9, for example, recognizes unmethylated deoxycytidyl
      phosphate-deoxyguanosine (CpG) dinucleotides that are common in bacterial and
      some viral nucleic acids, whereas TLR3 recognizes double-stranded RNA and
      TLR7/TLR8 recognize single-stranded RNA, which would be found during viral
      replication. We were interested in whether TLR3, TLR9, and the related TLR9
      family members TLR7/TLR8 might play a role in antiviral immune defense at the
      mucosal epithelial surface of the lower female reproductive tract. We studied
      cervical epithelial cells and found that they expressed mRNA for TLR3, TLR9, and
      TLR7, but had only a weak signal for TLR8. For TLR3 and TLR9, protein expression
      was confirmed to be intracellular. When epithelial cells were incubated with
      polyinosine-polycytidylic acid and CpG oligodinucleotides, we observed dose
      dependent upregulation of interleukin-8 secretion. However, cells failed to
      respond to a variety of TLR7/TLR8 ligands. Polyinosine-polycytidylic acid also
      induced production of interferon-beta and chemokine C-C motif ligand 5, whereas
      CpG DNA did not. Cell activation by synthetic oligodinucleotides occurred only in
      response to the B class sequences, and required the presence of human-specific
      CpG motifs. In addition, responses to CpG oligodinucleotides could be inhibited
      by chloroquine, demonstrating the requirement for endosomal maturation. These
      data demonstrate that mucosal epithelial cells express functional TLR3 and TLR9,
      and suggest that these receptors play a role in regulating the proinflammatory
      cytokine and antiviral environment of the lower female reproductive tract during
      infection with viral and bacterial pathogens.

PMID- 16421231
TI  - Spatio-developmental distribution of the prion-like protein doppel in Mammalian
      testis: a comparative analysis focusing on its presence in the acrosome of
      spermatids.
AB  - The first prion-like protein doppel, officially designed as prion protein dublet,
      does not seem to be needed for prion disease progression, whereas its
      physiological function seems to be related to male fertility. Its expression is
      primarily detected in the male genital tract, and Prnd-inactivated male mice are
      sterile. We investigated the location of Doppel in the testis of various species
      of mammal to determine its physiological function. Doppel is expressed early
      during ontogenesis, and is found in both germ cells and Sertoli cells in mice,
      rats, boars, and humans. Doppel is permanently expressed in the Sertoli cells but
      at different levels according to species. Its expression in testicular germ cells
      was primarily detected in spermatids, with a transient presence in the acrosome.
      These data suggest that Doppel may play a physiological role in acrosome
      biogenesis and may be of use in studies of patients suffering from idiopathic
      infertility.

PMID- 16421232
TI  - High resolution mapping of ribosomal DNA in early mouse embryos by fluorescence
      in situ hybridization.
AB  - The nucleolar precursor bodies (NPBs) are numerous discrete entities present in
      the nuclei of early mammalian embryos, which structurally support active rRNA
      genes. However, whether all rRNA genes, including those not transcribed, are
      spatially associated with NPBs, and moreover what is the general arrangement of
      ribosomal DNA (rDNA) in early mouse embryos, still remain unanswered questions.
      In our study, we examined the localization of rDNA in transcriptionally silent
      (one-cell and early two-cell) and transcriptionally active (late two-cell) mouse
      embryos by highly sensitive fluorescence in situ hybridization with probes
      complementary to mouse rDNA repeats. The results obtained showed that
      irrespective of the rDNA transcriptional status, one or more NPBs per nucleus
      were not structurally associated with rDNA. These observations support the idea
      that NPBs are heterogeneous in their ability to recruit rRNA genes and thus to
      participate in reassembly of the mature nucleolus. As in somatic cells, and
      despite the absence of the characteristic nucleoli, the general arrangement of
      rRNA genes in early mouse embryos reflected the intensity of rDNA transcription.
      Ribosomal RNA genes were unequally distributed with respect to repeat putative
      copy numbers between nucleolar organizing region (NOR)-bearing chromosomes at the
      first cleavage division, and more strikingly, between sister chromatid NORs of a
      single nucleolar organizing chromosome. The latter indicates that sister
      chromatids might harbor various numbers of rRNA gene copies, and that the genes
      might be unequally distributed between the two blastomeres during the first
      cleavage mitosis.

PMID- 16421233
TI  - New insights into the biology of preeclampsia.
AB  - Despite recent research progress, the biology of preeclampsia is still poorly
      understood and neither effective prediction nor causal therapy have yet emerged.
      Nevertheless, recent studies have documented new and exciting pathophysiological
      mechanisms for the origin and development of preeclampsia. These studies provide
      a more differentiated view on alterations of particular peptide systems with
      strong impact on angiogenesis and cardiovascular regulation in this pregnancy
      disorder. With the identification of the antiangiogenic factor soluble fms-like
      tyrosine kinase 1 and the agonistic autoantibody to the angiotensin II type 1
      receptor, two factors have been described with a clear linkage to the development
      of the disease. This review focuses on the most recent and relevant insights into
      the biology of preeclampsia and develops hypotheses regarding possible links
      between the reported aspects of preeclampsia.

PMID- 16421234
TI  - Molecular biology of ovarian aromatase in sex reversal: complementary DNA and 5'
      flanking region isolation and differential expression of ovarian aromatase in the
      gilthead seabream (Sparus aurata).
AB  - To elucidate the involvement of aromatase in sex reversal, the gilthead seabream
      ovarian P450 aromatase (cyp19a1a) cDNA and its 5'-flanking region were isolated
      and characterized. Northern blot analysis revealed that only one cyp19a1a
      transcript (2.0 kb) is expressed in the ovary. Four cAMP-responsive elements were
      identified at the 5'-flanking region of seabream cyp19a1a indicating a high
      potential to respond to gonadotropin signaling. Studying the seasonal profile,
      two expression peaks of cyp19a1a transcripts in the ovarian tissues were found in
      July (about 15000 copies/ng total RNA) for ambisexual fish and in December (about
      12000 copies/ng total RNA) for spawning females. Starting from September,
      transcript levels of cyp19a1a in the ovarian portions of the male-developing
      gonads gradually decreased. Furthermore, the ovarian portions of the female
      gonads expressed cyp19a1a at a significantly higher level than the ovarian
      portions of the male gonads after November. Taken together with levels of plasma
      estradiol in reversing females being significantly higher than those in
      developing males, the above results reinforce the importance of cyp19a1a in sex
      reversal. In vitro exposure of ovarian fragments to gonadotropins (hCG) at 1, 10,
      and 100 IU/ml significantly (P < 0.05) upregulated cyp19a1a expression.
      Additionally, expression of cyp19a1a displayed a stronger and significant
      correlation with the transcript expression of ovarian Lh receptor rather than Fsh
      receptor during the ambisexual stage. Our results indicate that the differential
      expression of cyp19a1a gene is associated with sex reversal and that gonadotropin
      signals (particularly Lh) may serve as major players in regulating the expression
      of cyp19a1a during the process of sex reversal.

PMID- 16421235
TI  - Modeling the sexual transmissibility of human papillomavirus infection using
      stochastic computer simulation and empirical data from a cohort study of young
      women in Montreal, Canada.
AB  - The authors estimated plausible ranges of the probability of human papillomavirus
      (HPV) transmission per coital act among newly forming couples by using stochastic
      computer simulation. Comparative empirical data were obtained in 1996-2001 from a
      cohort study of female university students in Montreal, Canada. Female prevalence
      and frequency of sexual intercourse and condom use were set equal to those in the
      cohort. Simulations included 240 combinations of male prevalence, the relative
      risk for protected versus unprotected sex, and per-act transmission
      probabilities. Those that produced expected HPV incidence within the 95%
      confidence interval observed in the cohort were selected. The observed 6-month
      cumulative incidence following acquisition of a new partner was 17.0% (95%
      confidence interval: 11.4, 23.0). Expected incidences consistent with those from
      cohort findings occurred in 54/240 simulations. The range of per-act transmission
      probabilities was 5-100% (median, 40%). Male HPV prevalence was the same as or
      greater than that for women in all consistent simulations. Varying condom
      effectiveness did not produce better-fitting data. This simulation suggests that
      HPV transmissibility is several-fold higher than that for other viral sexually
      transmitted infections such as human immunodeficiency virus or herpes simplex
      virus 2. With high transmissibility, any potential protective effect of condoms
      would disappear over multiple intercourse acts, underlining the need for an
      effective HPV vaccine.

PMID- 16421236
TI  - Association of educational level with inflammatory markers in the Framingham
      Offspring Study.
AB  - Socioeconomic position consistently predicts coronary heart disease; however, the
      biologic mechanisms that may mediate this association are not well understood.
      The objective of this study was to determine whether socioeconomic position
      (measured as educational level) is associated with inflammatory risk factors for
      coronary heart disease, including C-reactive protein, interleukin-6, soluble
      intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and P
      selectin. The study sample included 2,729 participants (53.4% women; mean age, 62
      +/- 10 years) from the US Framingham Offspring Study cohort who attended
      examination cycles 3 (1984-1987) and 7 (1998-2001) and provided educational
      attainment data. Inflammatory markers were measured in fasting serum samples.
      Multivariable linear regression analyses were performed, adjusting for potential
      confounders including age, sex, and clinical risk factors. In age- and sex
      adjusted analyses, educational attainment was significantly inversely associated
      with C-reactive protein (p < 0.0001), interleukin-6 (p < 0.0001), soluble
      intercellular adhesion molecule-1 (p < 0.0001), and monocyte chemoattractant
      protein-1 (p = 0.0004). After further adjustment for clinical risk factors,
      educational level remained significantly associated with C-reactive protein (p =
      0.0002), soluble intercellular adhesion molecule-1 (p = 0.01), and monocyte
      chemoattractant protein-1 (p = 0.01). In conclusion, educational attainment is
      associated with inflammatory risk factors for coronary heart disease. The
      association provides evidence suggestive of a biologic pathway by which
      socioeconomic position may predispose to coronary heart disease.

PMID- 16421237
TI  - Incidence and duration of group B Streptococcus by serotype among male and female
      college students living in a single dormitory.
AB  - Group B Streptococcus causes a variety of morbid and sometimes fatal conditions
      affecting individuals of all age groups. There are nine known serotypes of this
      Gram-positive coccus but few estimates of the incidence and duration of its
      colonization and none by serotype in the literature. In 2001, the authors
      conducted a prospective cohort study among 257 men and women living in a single
      dormitory in Ann Arbor, Michigan. The 3-week incidence with any serotype was
      11.3% (+/-3.9%) among women and 8.8% (+/-3.0%) among men; 3-week incidence rates
      were highest for serotype V (4.7% for women and 3.5% for men) and type Ia (2.3%
      for women and 2.4% for men), with no significant differences by gender. The
      estimated average duration of any group B Streptococcus colonization was longer
      for women (13.7 weeks) than men (8.5 weeks); serotype Ia was carried an average
      of 6.5 weeks longer in women, and serotype III was carried 4.9 weeks longer.
      Colonization with more than one serotype occurred significantly less than would
      be expected by chance (p <<< 0.001). Based on the overall incidence, transmission
      occurred between roommate pairs at the rate expected. Group B Streptococcus
      colonization is frequent and dynamic, but it is not transmitted by casual
      contact.

PMID- 16421238
TI  - Assessment of delay in age-appropriate vaccination using survival analysis.
AB  - Assessment of delay in age-appropriate vaccination provides more information
      about timeliness of vaccination than up-to-date vaccination coverage. The authors
      applied survival analysis methods to data from a vaccination coverage survey
      among children aged 13-59 months conducted in Argentina in 2002. By age 19
      months, 43% of children (95% confidence interval (CI): 40, 46) were vaccinated
      with the fourth dose of diphtheria, tetanus, and pertussis (DTP4). By age 13
      months, 55% of children (95% CI: 52, 57) were vaccinated with measles-containing
      vaccine. By age 7 months, 33% of children (95% CI: 27, 40) were vaccinated with
      the third dose of hepatitis B. Compared with firstborn children, third children
      were more likely to be delayed for DTP4 (relative risk (RR) = 1.41, 95% CI: 1.22,
      1.62), measles-containing vaccine (RR = 1.54, 95% CI: 1.32, 1.78), and the third
      dose of hepatitis B (RR = 1.31, 95% CI: 1.03, 1.67). Children whose caregivers
      had completed secondary school were less likely to be delayed for DTP4 (RR =
      0.68, 95% CI: 0.52, 0.90) compared with those whose caregivers had not completed
      primary school. Survival analysis methods were helpful in measuring vaccine
      uptake and should be considered in future surveys when assessing delay in age
      appropriate vaccination.

PMID- 16421239
TI  - A pooled analysis of second primary pancreatic cancer.
AB  - Studies of pancreatic cancer in the setting of second primary malignant neoplasms
      can provide etiologic clues. An international multicenter study was carried out
      using data from 13 cancer registries with a registration period up to year 2000.
      Cancer patients were followed up from the initial cancer diagnosis, and the
      occurrence of second primary malignant neoplasms was compared with expected
      values derived from local rates, adjusting for age, sex, and period of diagnosis.
      Results from individual registries were pooled by use of a fixed-effects model.
      People were at higher risk of developing pancreatic cancer within 10 years of a
      diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix,
      corpus uteri, bladder, and eye and 10 years or later following a diagnosis of
      cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus
      uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non
      Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related
      cancers, confirming the etiologic role of tobacco. The associations with uterine
      and ovarian cancers suggest that reproductive factors might be implicated in
      pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients
      observed among several types of cancer implies a role of genetic factors.
      Radiotherapy is also suggested as a risk factor.

PMID- 16421240
TI  - Risk of second primary malignancies in women with papillary thyroid cancer.
AB  - Second malignancies in women diagnosed with thyroid cancer are of concern given
      the young average age at diagnosis and excellent survival. Data from the
      California Cancer Registry were used to evaluate the risk of second primary
      cancers among a retrospective population-based cohort of 10,932 women diagnosed
      with papillary thyroid cancer between 1988 and 1999. Follow-up was calculated
      from 2 months until the diagnosis of a second primary cancer, death, loss to
      follow-up, or December 31, 1999, whichever occurred first. Standardized incidence
      ratios, based on age-specific cancer incidence rates for California women, were
      calculated. During a total of 50,938 person-years of follow-up (mean: 4.7 years),
      279 women developed a second primary cancer. The incidence of invasive breast
      cancer was not elevated compared with California women overall (standardized
      incidence ratio (SIR) = 0.9, 95% confidence interval (CI): 0.7, 1.1) or when
      stratified by age, race/ethnicity, follow-up, or radiation treatment. An excess
      of in situ breast cancer (SIR = 1.6, 95% CI: 1.0, 2.4), kidney cancer (SIR = 3.9,
      95% CI: 2.2, 6.3), and melanoma (SIR = 2.1, 95% CI: 1.3, 3.2) limited to the
      first 5 years after diagnosis was observed. Women with papillary thyroid cancer
      are at increased risk of in situ, but not invasive, breast cancer, kidney cancer,
      and melanoma.

PMID- 16421241
TI  - Drug dependence enviromics: job strain in the work environment and risk of
      becoming drug-dependent.
AB  - In a prospective epidemiologic study of a sample of young adults, the authors
      estimated the risks of being drug-dependent and becoming drug-dependent in
      relation to the psychosocial work environment encountered during young adulthood.
      Data were obtained from two young adult assessments of 2,311 children who entered
      the first grade of primary school in 1985-1986. A total of 1,692 participants
      completed the first young adult assessment (YAT0) in 2000-2002, and a follow-up
      young adult assessment (YAT1) was completed approximately 1 year later. Work
      environments characterized by high job strain (low job control combined with high
      job demands assessed at YAT0) signaled a 2- to 3-fold excess risk of being drug
      dependent (adjusted prevalence ratio = 2.3, 95% confidence interval: 1.4, 4.0).
      In reestimation for 861 young adults (61% female) with no drug dependence at
      YAT0, low job control alone was associated with a 2- to 3-fold excess risk of
      developing drug dependence (adjusted relative risk = 2.6, 95% confidence
      interval: 1.1, 6.5) between YAT0 and YAT1. The relative risk estimates did not
      change appreciably with statistical adjustment for demographic covariates,
      individual drugs used, childhood predispositional traits, job characteristics,
      and measurements of socioeconomic status at three time points (first grade,
      adolescence, and young adulthood).

PMID- 16421242
TI  - Association of blood lead and tibia lead with blood pressure and hypertension in
      a community sample of older adults.
AB  - Few studies have compared associations of blood lead and tibia lead with blood
      pressure and hypertension, and associations have differed in samples with
      occupational exposure compared with those with mainly environmental lead
      exposure. African Americans have been underrepresented in prior studies. The
      authors performed a cross-sectional analysis of 2001-2002 data from a community
      based cohort in Baltimore, Maryland, of 964 men and women aged 50-70 years (40%
      African American, 55% White, 5% other race/ethnicity) to evaluate associations of
      blood lead and tibia lead with systolic and diastolic blood pressure and
      hypertension while adjusting for a large set of potential confounding variables.
      Blood lead was a strong and consistent predictor of both systolic and diastolic
      blood pressure in models adjusted and not adjusted for race/ethnicity and
      socioeconomic status. Tibia lead was associated with hypertension status before
      adjustment for race/ethnicity and socioeconomic status (p = 0.01); after such
      adjustment, the association was borderline significant (p = 0.09). Propensity
      score analysis suggested that standard regression analysis may have exaggerated
      the attenuation. These findings are discussed in the context of complex causal
      pathways. The data suggest that lead has an acute effect on blood pressure via
      recent dose and a chronic effect on hypertension risk via cumulative dose.

PMID- 16421243
TI  - Reliability of self-reported ancestry among siblings: implications for genetic
      association studies.
AB  - This study investigated the reliability of self-reported ancestry by comparing
      the interview responses of probands and their siblings. A total of 546 sibling
      pairs were ascertained in a family-based study of susceptibility genes for
      Parkinson's disease and asked to identify maternal and paternal countries of
      origin. Probands were recruited prospectively from the Department of Neurology of
      the Mayo Clinic in Rochester, Minnesota, from June 1, 1996, through May 31, 2005.
      Probands resided within Minnesota or one of the four surrounding states
      (Wisconsin, Iowa, South Dakota, North Dakota). Only 49 percent of these sibling
      pairs, primarily Caucasian, agreed completely on the countries of origin of both
      parents. The agreement increased to 68 percent when named countries were
      postcoded into six population genetic clusters (as previously defined by
      microsatellite markers). Self-reported ancestry may not be a reliable method to
      reduce the possible impact of population stratification in genetic association
      studies of outbred populations, such as in the United States.

PMID- 16421244
TI  - When is quarantine a useful control strategy for emerging infectious diseases?
AB  - The isolation and treatment of symptomatic individuals, coupled with the
      quarantining of individuals that have a high risk of having been infected,
      constitute two commonly used epidemic control measures. Although isolation is
      probably always a desirable public health measure, quarantine is more
      controversial. Mass quarantine can inflict significant social, psychological, and
      economic costs without resulting in the detection of many infected individuals.
      The authors use probabilistic models to determine the conditions under which
      quarantine is expected to be useful. Results demonstrate that the number of
      infections averted (per initially infected individual) through the use of
      quarantine is expected to be very low provided that isolation is effective, but
      it increases abruptly and at an accelerating rate as the effectiveness of
      isolation diminishes. When isolation is ineffective, the use of quarantine will
      be most beneficial when there is significant asymptomatic transmission and if the
      asymptomatic period is neither very long nor very short.

PMID- 16421245
TI  - Neighborhood conditions and risk of incident lower-body functional limitations
      among middle-aged African Americans.
AB  - The authors investigated the association between observed neighborhood conditions
      and lower-body functional limitations (LBFLs) using data from 563 subjects of the
      African-American Health Study. This population-based cohort received in-home
      evaluations. Five items involving LBFL were obtained at baseline (2000-2001) and
      3 years later. Subjects were considered to have LBFL if they reported difficulty
      on at least two of the five tasks. The external appearance of the block the
      respondent lived on was rated during sample enumeration by use of five items
      (rated excellent, good, fair, or poor). Of 563 subjects with 0-1 LBFL at
      baseline, 15% and 14% lived in neighborhoods with 4-5 and 2-3 fair/poor
      conditions, respectively. Logistic regression adjusting for propensity scores
      showed that persons who lived in neighborhoods with 4-5 versus 0-1 fair/poor
      condition were 3.07 times (95% confidence interval: 1.58, 5.94) more likely to
      develop two or more LBFLs. The odds ratio was 2.24 (95% confidence interval:
      1.07, 4.70) when living in neighborhoods with 2-3 conditions versus 0-1 fair/poor
      condition. Odds ratios for individual neighborhood characteristics varied from
      3.45 (fair/poor street conditions) to 2.01 (fair/poor noise level). Sensitivity
      analyses showed the robustness of the findings. Poor neighborhood conditions
      appear to be an independent contributor to the risk of incident LBFLs in middle
      aged African Americans.

PMID- 16421246
TI  - Chronic liver disease is triggered by taurine transporter knockout in the mouse.
AB  - Taurine is an abundant organic osmolyte with antioxidant and immunomodulatory
      properties. Its role in the pathogenesis of chronic liver disease is unknown. The
      liver phenotype was studied in taurine transporter knockout (taut-/-) mice.
      Hepatic taurine levels were ~21, 15 and 6 mumol/g liver wet weight in adult wild
      type, heterozygous (taut+/-) and homozygous (taut-/-) mice, respectively.
      Immunoelectronmicroscopy revealed an almost complete depletion of taurine in
      Kupffer and sinusoidal endothelial cells, but not in parenchymal cells of (taut-/
      ) mice. Compared with wild-type mice, (taut-/-) and (taut+/-) mice developed
      moderate unspecific hepatitis and liver fibrosis with increased frequency of
      neoplastic lesions beyond 1 year of age. Liver disease in (taut-/-) mice was
      characterized by hepatocyte apoptosis, activation of the CD95 system, elevated
      plasma TNF-alpha levels, hepatic stellate cell and oval cell proliferation, and
      severe mitochondrial abnormalities in liver parenchymal cells. Mitochondrial
      dysfunction was suggested by a significantly lower respiratory control ratio in
      isolated mitochondria from (taut-/-) mice. Taut knockout had no effect on taurine
      conjugated bile acids in bile; however, the relative amount of cholate-conjugates
      acid was decreased at the expense of 7-keto-cholate-conjugates. In conclusion,
      taurine deficiency due to defective taurine transport triggers chronic liver
      disease, which may involve mitochondrial dysfunction.

PMID- 16421247
TI  - CD99 acts as an oncosuppressor in osteosarcoma.
AB  - CD99 was recently reported to be under control of the osteoblast-specific
      transcription factor Cbfa1 (RUNX2) in osteoblasts, suggesting a role in the phato
      physiology of these cells. No extensive information is available on the role(s)
      of this molecule in malignant phenotype, and osteosarcoma, in particular, has
      never been studied. We report that in 11 different cell lines and 17 clinical
      samples CD99 expression is either undetectable or very low. Being expressed in
      the normal counterpart, we tested the hypothesis that CD99 down-regulation may
      have a role in osteosarcoma development and progression. CD99-forced expression
      in two osteosarcoma cell lines significantly reduced resistance to anoikis,
      inhibited growth in anchorage independence as well as cell migration, and led to
      abrogation of tumorigenic and metastatic ability. Therefore, the molecule acts as
      a potent suppressor of malignancy in osteosarcoma. CD99 gene transfection induces
      caveolin-1 up-regulation and the two molecules were found to colocalize on the
      cell surface. Treatment with antisense oligonucleotides to caveolin-1 abrogates
      the effects of CD99 on migration. The findings point to an antioncogenic role for
      CD99 in osteosarcoma, likely through the regulation of caveolin-1 and inhibition
      of c-Src kinase activity.

PMID- 16421248
TI  - A genetic dissection of Aip1p's interactions leads to a model for Aip1p-cofilin
      cooperative activities.
AB  - Actin interacting protein 1 (Aip1p) and cofilin cooperate to disassemble actin
      filaments in vitro and are thought to promote rapid turnover of actin networks in
      vivo. The precise method by which Aip1p participates in these activities has not
      been defined, although severing and barbed-end capping of actin filaments have
      been proposed. To better describe the mechanisms and biological consequences of
      Aip1p activities, we undertook an extensive mutagenesis of AIP1 aimed at
      disrupting and mapping Aip1p interactions. Site-directed mutagenesis suggested
      that Aip1p has two actin binding sites, the primary actin binding site lies on
      the edge of its N-terminal beta-propeller and a secondary actin binding site lies
      in a comparable location on its C-terminal beta-propeller. Random mutagenesis
      followed by screening for separation of function mutants led to the
      identification of several mutants specifically defective for interacting with
      cofilin but still able to interact with actin. These mutants suggested that
      cofilin binds across the cleft between the two propeller domains, leaving the
      actin binding sites exposed and flanking the cofilin binding site. Biochemical,
      genetic, and cell biological analyses confirmed that the actin binding- and
      cofilin binding-specific mutants are functionally defective, whereas the genetic
      analyses further suggested a role for Aip1p in an early, internalization step of
      endocytosis. A complementary, unbiased molecular modeling approach was used to
      derive putative structures for the Aip1p-cofilin complex, the most stable of
      which is completely consistent with the mutagenesis data. We theorize that Aip1p
      severing activity may involve simultaneous binding to two actin subunits with
      cofilin wedged between the two actin binding sites of the N- and C-terminal
      propeller domains.

PMID- 16421249
TI  - Rgf1p is a specific Rho1-GEF that coordinates cell polarization with cell wall
      biogenesis in fission yeast.
AB  - Rho1p regulates cell integrity by controlling the actin cytoskeleton and cell
      wall synthesis. We have identified a new GEF, designated Rgf1p, which
      specifically regulates Rho1p during polarized growth. The phenotype of rgf1 null
      cells was very similar to that seen after depletion of Rho1p, 30% of cells being
      lysed. In addition, rgf1(+) deletion caused hypersensitivity to the antifungal
      drug Caspofungin and defects in the establishment of bipolar growth. rho1(+), but
      none of the other GTPases of the Rho-family, suppressed the rgf1Delta phenotypes.
      Moreover, deletion of rgf1(+) suppressed the severe growth defect in rga1(+) null
      mutants (a Rho1-GAP, negative regulator). Rgf1p and Rho1p coimmunoprecipitated
      and overexpression of rgf1(+) specifically increased the GTP-bound Rho1p; it
      caused changes in cell morphology, and a large increase in beta(1,3)-glucan
      synthase activity. These effects were similar to those elicited when the
      hyperactive rho1-G15V allele was expressed. A genetic relationship was observed
      between Rgf1p, Bgs4p (beta[1,3]-glucan synthase), and Pck1p (protein kinase C
      [PKC] homologue); Bgs4p and Pck1p suppressed the hypersensitivity to Caspofungin
      in rgf1Delta mutants. Rgf1p localized to the growing ends and the septum, where
      Rho1, Pck1p, and Bgs4p are known to function. Our results suggest that Rgf1p
      probably activates the Rho functions necessary for coordinating actin deposition
      with cell wall biosynthesis during bipolar growth, allowing the cells to remodel
      their wall without risk of rupture.

PMID- 16421250
TI  - The F-box protein Dia2 regulates DNA replication.
AB  - Ubiquitin-mediated proteolysis plays a key role in many pathways inside the cell
      and is particularly important in regulating cell cycle transitions. SCF
      (Skp1/Cul1/F-box protein) complexes are modular ubiquitin ligases whose
      specificity is determined by a substrate-binding F-box protein. Dia2 is a
      Saccharomyces cerevisiae F-box protein previously described to play a role in
      invasive growth and pheromone response pathways. We find that deletion of DIA2
      renders cells cold-sensitive and subject to defects in cell cycle progression,
      including premature S-phase entry. Consistent with a role in regulating DNA
      replication, the Dia2 protein binds replication origins. Furthermore, the dia2
      mutant accumulates DNA damage in both S and G2/M phases of the cell cycle. These
      defects are likely a result of the absence of SCF(Dia2) activity, as a Dia2
      DeltaF-box mutant shows similar phenotypes. Interestingly, prolonging G1-phase in
      dia2 cells prevents the accumulation of DNA damage in S-phase. We propose that
      Dia2 is an origin-binding protein that plays a role in regulating DNA
      replication.

PMID- 16421251
TI  - Assortment of phosphatidylinositol 3-kinase complexes--Atg14p directs association
      of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, two similar phosphatidylinositol 3-kinase
      complexes (complexes I and II) function in distinct biological processes, complex
      I in autophagy and complex II in the vacuolar protein sorting via endosomes.
      Atg14p is only integrated into complex I, likely facilitating the function of
      complex I in autophagy. Deletion analysis of Atg14p revealed that N-terminal
      region containing the coiled-coil structures was essential and sufficient for
      autophagy. Atg14p localized to pre-autophagosomal structure (PAS) and vacuolar
      membranes, whereas Vps38p, a component specific to complex II, localized to
      endosomes and vacuolar membranes. Vps34p and Vps30p, components shared by the two
      complexes, localized to the PAS, vacuolar membranes, and several punctate
      structures that included endosomes. The localization of these components to the
      PAS was Atg14p dependent but not dependent on Vps38p. Conversely, localization of
      these proteins to endosomes required Vps38p but not Atg14p. Vps15p, regulatory
      subunit of the Vps34p complexes, localized to the PAS, vacuolar membranes, and
      punctate structures independent of both Atg14p and Vps38p. Together, these
      results indicate that complexes I and II function in distinct biological
      processes by localizing to specific compartments in a manner mediated by specific
      components of each complex, Atg14p and Vps38p, respectively.

PMID- 16421252
TI  - Distinct roles of PI(3,4,5)P3 during chemoattractant signaling in Dictyostelium:
      a quantitative in vivo analysis by inhibition of PI3-kinase.
AB  - The role of PI(3,4,5)P(3) in Dictyostelium signal transduction and chemotaxis was
      investigated using the PI3-kinase inhibitor LY294002 and pi3k-null cells. The
      increase of PI(3,4,5)P(3) levels after stimulation with the chemoattractant cAMP
      was blocked >95% by 60 microM LY294002 with half-maximal effect at 5 microM. This
      correlated well with the inhibition of the membrane translocation of the PH
      domain protein, PHcracGFP. LY294002 did not reduce cAMP-mediated cGMP production,
      but significantly reduced the cAMP response up to 75% in wild type and completely
      in pi3k-null cells. LY294002-treated cells were round, not elongated as control
      cells. Interestingly, cAMP induced a time and dose-dependent recovery of cell
      elongation. These elongated LY294002-treated wild-type and pi3k-null cells
      exhibited chemotactic orientation toward cAMP that is statistically identical to
      chemotactic orientation of control cells. In control cells, PHcrac-GFP and F
      actin colocalize upon cAMP stimulation. However, inhibition of PI3-kinases does
      not affect the first phase of the actin polymerization at a wide range of
      chemoattractant concentrations. Our data show that severe inhibition of cAMP
      mediated PI(3,4,5)P(3) accumulation leads to inhibition of cAMP relay, cell
      elongation and cell aggregation, but has no detectable effect on chemotactic
      orientation, provided that cAMP had sufficient time to induce cell elongation.

PMID- 16421256
TI  - The differences in panoramic mandibular indices and fractal dimension between
      patients with and without spinal osteoporosis.
AB  - OBJECTIVES: The aims of this study were to evaluate the relationship between
      osteoporosis, oral signs, body mass index and age; and to assess the possibility
      of using these parameters as an indicator of post-menopausal osteoporosis. The
      oral signs were panoramic-based mandibular indices, such as cortical width,
      cortical index, panoramic mandibular index and mandibular crest resorption
      degree; the number of teeth and fractal dimension analysis. METHODS: Forty-eight
      post-menopausal women between the ages of 40 years and 64 years were evaluated.
      Mandibular indices and the number of mandibular teeth were measured and evaluated
      from panoramic radiographs and fractal dimension was calculated from the direct
      digital periapical radiographs of the mandibular premolar-molar region in box
      counting method. Weight, height, menopausal status and age of the patients were
      recorded by questionnaire. Bone mineral densities of the patients were measured
      with dual energy X-ray absorptiometry. RESULTS: In this study there were no
      statistically significant differences between the osteoporotic and non
      osteoporotic patients for cortical width, panoramic mandibular index, alveolar
      crest resorption degree, fractal dimension and the number of mandibular teeth,
      but there was a difference for cortical index. Binary logistic regression
      analyses demonstrated that age (P = 0.015) was an important risk factor for
      osteoporosis. CONCLUSION: The results of this study demonstrated that
      osteoporotic patients were more likely to have altered inferior cortex morphology
      than non-osteoporotic patients and age is an important risk factor for
      osteoporosis.

PMID- 16421257
TI  - Reproducibility of and file format effect on digital subtraction radiography of
      simulated external root resorptions.
AB  - OBJECTIVE: To evaluate, in simulated external root resorptions (ERR), two factors
      that may affect results of digital subtraction radiography (DSR): (1)
      intraobserver and interobserver reproducibility and (2) effects of digital file
      formats (TIFF, BMP and JPEG) on the estimation of mineral loss. METHODS: Eleven
      incisors were radiographed three times (NR, no resorption; SR, small--#1/4 round
      bur; and LR, large--#2 round bur) on standardized projections. The resulting
      images were reproduced and saved as TIFF, JPEG and BMP file formats. The pairs of
      TIFF images (NR x SR and NR x LR) were subtracted three times at 1 week intervals
      by three observers. One observer subtracted pairs of images (NR x SR and NR x LR)
      for all file formats. For each subtraction the resorption area was selected and
      mean pixel density values were calculated. RESULTS: Analysis of variance (ANOVA)
      (P = 0.05) showed no statistical differences for intraobserver and interobserver
      values. Mean pixel density values were: observer A, 121.60 +/- 2.56 (NR x SR) and
      111.84 +/- 4.04 (NR x LR); observer B, 121.86 +/- 2.50 (NR x SR) and 110.92 +/-
      3.36 (NR x LR); and observer C, 121.70 +/- 2.39 (NR x SR) and 111.10 +/- 2.67 (NR
      x LR). Also, no statistical differences were found between file formats for LR
      (TIFF, 110.88 +/- 2.79; JPEG, 111.35 +/- 3.35; BMP, 111.00 +/- 2.70) and for SR
      between TIFF (121.30 +/- 2.34) and JPEG (120.46 +/- 1.51) or BMP (121.67 +/-
      2.18) file formats. Differences were found between the JPEG and BMP groups.
      CONCLUSIONS: DSR is reproducible in simulated ERR, and JPEG or BMP file formats
      do not affect results.

PMID- 16421258
TI  - Evaluation of scatter dose of dental titanium implants exposed to photon beams of
      different energies and irradiation angles in head and neck radiotherapy.
AB  - OBJECTIVES: In this study, quantification of backscatter doses between scattering
      titanium dental implant and the thermoluminescent dosimeter (TLD(100)) radiation
      detector at axial beam irradiation-angle range of 0-90 degrees in head and neck
      radiotherapy is done to evaluate irradiation angle dependency of dose enhancement
      contributing to osteoradionecrosis. METHODS: A cylindrical titanium dental
      implant with diameter of 4 mm and length of 9 mm was implanted into a specially
      designed human mandible phantom with a TLD100 chip placed on the buccal site and
      irradiated with 6 MV X, 25 MV X and Co-60 gamma sources at 19 different
      irradiation angles. RESULTS: Dose enhancement on a buccal site of the titanium
      implant depends on the incident beam angle. At angles of 65 degrees, 60 degrees
      and 40 degrees the maximum detected scatter doses over the titanium implant are
      36%, 32% and 23% for Co-60 gamma, 6 MV X-ray and 25 MV X-ray, respectively. The
      dose enhancement at different beam angles was less pronounced in 25 MV X and more
      pronounced in Co-60 gamma irradiation. CONCLUSIONS: For the different radiation
      beams studied, the irradiation angle between scattering titanium dental implants
      and the central axis does not significantly affect the total dose that may lead
      to osteoradionecrosis of the mandible.

PMID- 16421253
TI  - Rab1 defines a novel pathway connecting the pre-Golgi intermediate compartment
      with the cell periphery.
AB  - The function of the pre-Golgi intermediate compartment (IC) and its relationship
      with the endoplasmic reticulum (ER) and Golgi remain only partially understood.
      Here, we report striking segregation of IC domains in polarized PC12 cells that
      develop neurite-like processes. Differentiation involves expansion of the IC and
      movement of Rab1-containing tubules to the growth cones of the neurites, whereas
      p58- and COPI-positive IC elements, like rough ER and Golgi, remain in the cell
      body. Exclusion of Rab1 effectors p115 and GM130 from the neurites further
      indicated that the centrifugal, Rab1-mediated pathway has functions that are not
      directly related to ER-to-Golgi trafficking. Disassembly of COPI coats did not
      affect this pathway but resulted in missorting of p58 to the neurites. Live cell
      imaging showed that green fluorescent protein (GFP)-Rab1A-containing IC elements
      move bidirectionally both within the neurites and cell bodies, interconnecting
      different ER exit sites and the cis-Golgi region. Moreover, in nonpolarized cells
      GFP-Rab1A-positive tubules moved centrifugally towards the cell cortex.
      Hydroxymethylglutaryl-CoA reductase, the key enzyme of cholesterol biosynthesis,
      colocalized with slowly sedimenting, Rab1-enriched membranes when the IC
      subdomains were separated by velocity sedimentation. These results reveal a novel
      pathway directly connecting the IC with the cell periphery and suggest that this
      Rab1-mediated pathway is linked to the dynamics of smooth ER.

PMID- 16421254
TI  - Calpain mediates a von Hippel-Lindau protein-independent destruction of hypoxia
      inducible factor-1alpha.
AB  - Hypoxia-inducible factor 1 (HIF-1) is controlled through stability regulation of
      its alpha subunit, which is expressed under hypoxia but degraded under normoxia.
      Degradation of HIF-1alpha requires association of the von Hippel Lindau protein
      (pVHL) to provoke ubiquitination followed by proteasomal digestion. Besides
      hypoxia, nitric oxide (NO) stabilizes HIF-1alpha under normoxia but destabilizes
      the protein under hypoxia. To understand the role of NO under hypoxia we made use
      of pVHL-deficient renal carcinoma cells (RCC4) that show a high steady state HIF
      1alpha expression under normoxia. Exposing RCC4 cells to hypoxia in combination
      with the NO donor DETA-NO (2,2'-(hydroxynitrosohydrazono) bis-ethanimine), but
      not hypoxia or DETA-NO alone, decreased HIF-1alpha protein and attenuated HIF-1
      transactivation. Mechanistically, we noticed a role of calpain because calpain
      inhibitors reversed HIF-1alpha degradation. Furthermore, chelating intracellular
      calcium attenuated HIF-1alpha destruction by hypoxia/DETA-NO, whereas a calcium
      increase was sufficient to lower the amount of HIF-1alpha even under normoxia. An
      active role of calpain in lowering HIF-1alpha amount was also evident in pVHL
      containing human embryonic kidney cells when the calcium pump inhibitor
      thapsigargin reduced HIF-1alpha that was stabilized by the prolyl hydroxylase
      inhibitor dimethyloxalylglycine (DMOG). We conclude that calcium contributes to
      HIF-1alpha destruction involving the calpain system.

PMID- 16421259
TI  - Correlation between the incidence of central nodal necrosis in cervical lymph
      node metastasis and the extent of differentiation in oral squamous cell
      carcinoma.
AB  - OBJECTIVES: To investigate the incidence of central nodal necrosis (CNN) in the
      cervical lymph nodes of patients with oral squamous cell carcinoma (SCC) and the
      factors that influence the formation of CNN. METHODS: Lymph nodes shown as CNN on
      computed tomography (CT) films in 107 lymph nodes from 27 patients with oral SCC
      were selected. Lymph nodes with CNN on CT films were compared with the
      pathological findings of lymph nodes on specimens. We compared many kinds of
      factors influencing the formation of CNN, including the differentiated type, with
      the incidence of CNN. RESULTS: Significant relationships were found between the
      incidence of CNN in metastatic lymph nodes and the presence of well
      differentiated SCC and the presence of keratinization in tumour cells.
      CONCLUSIONS: The results indicated that if a patient had SCC with low-grade
      differentiation, CNN in small lymph nodes would be difficult to detect on CT
      scan. Therefore, noting changes in lymph node density in the absence of CNN on CT
      scans is necessary in case the primary tumour is low-grade SCC.

PMID- 16421255
TI  - SUMOylation of the corepressor N-CoR modulates its capacity to repress
      transcription.
AB  - In the absence of ligands the corepressor N-CoR mediates transcriptional
      repression by some nuclear hormone receptors. Several protein-protein
      interactions of N-CoR are known, of which mainly complex formation with histone
      deacetylases (HDACs) leads to the repression of target genes. On the other hand,
      the role of posttranslational modifications in corepressor function is not well
      established. Here, we show that N-CoR is modified by Sumo-1. We found SUMO-E2
      conjugating enzyme Ubc9 and SUMO-E3 ligase Pias1 as novel N-CoR interaction
      partners. The SANT1 domain of N-CoR was found to mediate this interaction. We
      show that K152, K1117, and K1330 of N-CoR can be conjugated to SUMO and that
      mutation of all sites is necessary to fully block SUMOylation in vitro. Because
      these lysine residues are located within repression domains I and III,
      respectively, we investigated a possible correlation between the functions of the
      repression domains and SUMOylation. Coexpression of Ubc9 protein resulted in
      enhanced N-CoR-dependent transcriptional repression. Studies using SUMOylation
      deficient N-CoR RDI mutants suggest that SUMO modification contributes to
      repression by N-CoR. Mutation of K152 to R in RD1, for example, not only
      significantly reduced repression of a reporter gene, but also abolished the
      effect of Ubc9 on transcriptional repression.

PMID- 16421260
TI  - Interpretation of scintigraphic findings of oral malignant tumours with a new
      scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m
      MIBI).
AB  - OBJECTIVES: The purpose of this study was to investigate the usefulness of a new
      scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m
      MIBI) for the diagnosis of malignant tumours of the head and neck. METHODS:
      Scintigraphy with Tc-99m-MIBI was performed in 19 patients with malignant tumours
      of the head and neck. Factors of the early and delayed static scans (hot, warm or
      cold uptake), the early and delayed retention indexes, the blood flow index and
      the tumour retention index were obtained from Tc-99m-MIBI scintigraphy. Tumour
      retention indexes were classified into three grades; slightly (>0.9), moderately
      (0.9-0.8) and severely (0.8>) decreased. Grade of tissue differentiation of
      tumour (well, moderately or poorly differentiated) and tumour size (T1
      approximately T4) were examined using the excised tumour. Scintigraphic indexes
      and tumour characteristics were compared. RESULTS: The early static scan and
      tumour size showed a correlation with the blood flow index. However, the delayed
      static scan did not show any relationship with blood flow index and tumour size.
      The tumour retention index had a tendency to decrease in malignant tumours, and
      showed a significant correlation with the grade of tissue differentiation of the
      tumour. CONCLUSIONS: The tendency of the tumour retention index to decrease in Tc
      99m-MIBI scintigraphy showed the malignancy of tumour and would be useful for the
      diagnosis of malignant tumours of the head and neck.

PMID- 16421261
TI  - Pre-operative radiographic evaluation of lower third molars with computed
      tomography.
AB  - OBJECTIVES: To report radiographic findings of examinations with computed
      tomography (CT) of impacted lower third molars with an intimate relation to the
      mandibular canal and to investigate how findings of a dark band across the roots
      of the lower third molar on panoramic views correspond to the CT findings.
      METHODS: CT images of 90 lower third molars (64 patients, mean age 34.6 years) in
      which plain radiography was insufficient to allow determination of the precise
      anatomical relations were reviewed retrospectively. Panoramic views of 88 teeth
      existed; these images were interpreted independent of the CT examinations with
      respect to presence of a dark band across the roots. RESULTS: In 31% of the CT
      images, the course of the mandibular canal was buccal, in 33% lingual, in 26%
      inferior, and in 10% inter-radicular. The tooth was in contact with the
      mandibular canal in 94% and with the lingual cortex in 86%. In 23%, grooving of
      the root by the canal was judged to be present. In 63% of the cases where a dark
      band across the roots was observed on panoramic radiographs, CT revealed grooving
      of the root. CONCLUSIONS: Pre-operative CT of lower third molars is motivated in
      selected cases when plain radiography is inconclusive. The finding of a dark band
      across the roots on panoramic radiographs is an indicator of grooving of the
      tooth by the canal and justifies a pre-operative CT examination. The absence of
      dark bands on panoramic views does not exclude grooving of the roots.

PMID- 16421262
TI  - Impacted earring clip visible on panoramic radiograph.
AB  - Earrings are very popular jewelry and ear piercing is performed in very young
      children. Complications that have been reported in the literature are mainly
      dermatologic, ranging from embedded foreign body to pressure sores in the post
      auricular region. During panoramic radiographic evaluation, precise examination
      of this area can be used to determine the presence of foreign bodies. In this
      case, a patient referred to our clinic with panoramic film for an impacted third
      molar who was not aware of an earring clip impacted in her ear lobe is presented.

PMID- 16421263
TI  - Gunshot injury to the face with a missile lodged in the upper cervical spine
      without neurological deficit.
AB  - An unusual case of facial gunshot injury with the missile lodged in the cervical
      spinal canal, but without any neurological impairment is reported. The extent of
      tissue damage and missile track termination in a male patient who sustained
      gunshot trauma to the face was assessed by plain radiography and by CT scans. The
      patient was treated conservatively and observed for clinical manifestations of
      neurological deficit for 3 weeks. CT of the head and neck performed 13 years
      after injury with the three-dimensional (3D) reconstruction of skeletal elements
      revealed healed fractures of the right nasal bone, the labyrinth of the right
      ethmoid bone, and position of the missile on the medial aspect of the right
      lateral mass of the atlas. There was no migration of the missile during this
      period. This case report of gunshot wound to the face associated with injury of
      the cervical spine indicated possibility of survival and atypical absence of
      clinical manifestation that may occur even when a bullet remains in the spinal
      canal.

PMID- 16421264
TI  - A case of recurrent ameloblastoma developing in an autogenous iliac bone graft 20
      years after the initial treatment.
AB  - A case of recurrent ameloblastoma developing in an autogenous iliac bone graft 20
      years after radical resection of primary mandibular ameloblastoma is presented.
      This case showed extensive bony resorption extending throughout the auto-grafted
      bone. Seeding to the graft bone was suspected as a cause of the recurrence in the
      iliac bone graft because wide destruction of the graft bone was observed without
      any prior signs and symptoms of intraoral mucosa. Consequently, extensive
      resection of bone as well as adjacent soft tissue was performed. Persistent
      follow-up examination is essential for management of ameloblastoma.

PMID- 16421265
TI  - Pneumatization of the sphenoid sinus.
AB  - This paper describes a case of pneumatization of the sphenoid sinus in the
      pterygoid process and greater wing of the sphenoid bone, observed on a panoramic
      radiograph. Conventional radiographs and computerized tomography in axial and
      coronal sections confirmed the presence of the pneumatization of these
      structures.

PMID- 16421266
TI  - Pyle's disease: an incidental finding in a routine dental patient.
AB  - Pyle's disease (PD) or metaphyseal dysplasia is an extremely rare genetic
      disorder, transmitted as an autosomal recessive trait. The peculiarity of the
      disease is that the striking radiographic manifestations contrast with the
      relatively normal clinical features. The oral findings and radiographic features
      of the disease are not well documented. The present paper describes the
      radiographic features of Pyle's disease in a 17-year-old girl and draws attention
      to the findings in the jaw bones.

PMID- 16421267
TI  - The value of three-dimensional computed tomography in diagnosis and management of
      Jacob's disease.
AB  - This study reports a case of Jacob's disease characterized with limited mouth
      opening due to bilateral coronoid hyperplasia forming pseudojoints with zygomatic
      arches. Magnetic resonance (MR) examination of temporomandibular joint (TMJ) is
      usually the imaging method chosen in patients with such symptoms. However, the
      coronoid processes can not be displayed because they are not included in field of
      view in MR imaging of TMJ. For that reason, these patients may be treated for a
      misdiagnosis of TMJ disorders. In this study, the aetiology and diagnostic
      methods of Jacob's disease, the pre-operative/post-operative role of three
      dimensional computed tomography and some measurements used in diagnosis were
      evaluated.

PMID- 16421268
TI  - Probable keratocyst in a mandible from the late Roman era.
AB  - Odontogenic keratocysts, characterized by considerable local aggressiveness and
      high recurrence rates, account for 5-15% of all odontogenic cysts. This paper
      reviews the literature and describes the most important aspects of this type of
      cyst, a clinical example being given as way of illustration. We also report a
      paleopathological case featuring an osteolytic lesion where the characteristics
      are consistent with a keratocyst. The aim is thus to encourage odontologists to
      contribute to research in the field of paleopathology.

PMID- 16421269
TI  - Multiple radiographic projections in diagnosis of uncommon unerupted tooth.

PMID- 16421270
TI  - Genetic manipulation of an exogenous non-immunoglobulin protein by gene
      conversion machinery in a chicken B cell line.
AB  - During culture, a chicken B cell line DT40 spontaneously mutates immunoglobulin
      (Ig) genes by gene conversion, which involves activation-induced cytidine
      deaminase (AID)-dependent homologous recombination of the variable (V) region
      gene with upstream pseudo-V genes. To explore whether this mutation mechanism can
      target exogenous non-Ig genes, we generated DT40 lines that bears a gene
      conversion substrate comprising the green fluorescent protein (GFP) gene as a
      donor and the blue fluorescent protein (BFP) gene as an acceptor. A few percent
      of the initially BFP-expressing cells converted their fluorescence from blue to
      green after culture for 2-3 weeks when the substrate construct was integrated in
      the Ig light chain locus, but not in the ovalbumin locus. This was the result of
      AID-dependent and the GFP gene-templated gene conversion of the BFP gene, thereby
      leading to the introduction of various sizes of GFP-derived gene segment into the
      BFP gene. Thus, G/B construct may be used to visualize gene conversion events.
      After switching off AID expression in DT40 cells, the mutant clones were isolated
      stably and maintained with their mutations being fixed. Thus, the gene conversion
      machinery in DT40 cells will be a useful means to engineer non-Ig proteins by a
      type of DNA shuffling.

PMID- 16421271
TI  - Sub-plastidial localization of two different phage-type RNA polymerases in
      spinach chloroplasts.
AB  - Plant plastids contain a circular genome of approximately 150 kb organized into
      approximately 35 transcription units. The plastid genome is organized into
      nucleoids and attached to plastid membranes. This relatively small genome is
      transcribed by at least two different RNA polymerases, one being of the
      prokaryotic type and plastid-encoded (PEP), the other one being of the phage-type
      and nucleus-encoded (NEP). The presumed localization of a second phage-type RNA
      polymerase in plastids is still questionable. There is strong evidence for a
      sequential action of NEP and PEP enzymes during plant development attributing a
      prevailing role of NEP during early plant and plastid development, although NEP
      is present in mature chloroplasts. In the present paper, we have analysed two
      different NEP enzymes from spinach with respect to subcellular and intra
      plastidial localization in mature chloroplasts with the help of specific
      antibodies. Results show the presence of the two different NEP enzymes in mature
      chloroplasts. Both enzymes are entirely membrane bound but, unlike previously
      thought, this membrane binding is not mediated via DNA. This finding indicates
      that NEP enzymes are not found as elongating transcription complexes on the
      template DNA in mature chloroplasts and raises the question of their function in
      mature chloroplasts.

PMID- 16421272
TI  - 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (2'F-ANA) modified oligonucleotides
      (ON) effect highly efficient, and persistent, gene silencing.
AB  - To be effective in vivo, antisense oligonucleotides (AS ON) should be nuclease
      resistant, form stable ON/RNA duplexes and support ribonuclease H mediated
      heteroduplex cleavage, all with negligible non-specific effects on cell function.
      We report herein that AS ONs containing a 2'-deoxy-2'-fluoro-beta-D
      arabinonucleic acid (2'F-ANA) sugar modification not only meet these criteria,
      but have the added advantage of maintaining high intracellular concentrations for
      prolonged periods of time which appears to promote longer term gene silencing. To
      demonstrate this, we targeted the c-MYB protooncogene's mRNA in human leukemia
      cells with fully phosphorothioated 2'F-ANA-DNA chimeras (PS-2'FANA-DNA) and
      compared their gene silencing efficiency with AS ON containing unmodified
      nucleosides (PS-DNA). When delivered by nucleofection, chemically modified ON of
      both types effected a >90% knockdown of c-MYB mRNA and protein expression, but
      the PS-2'F-ANA-DNA were able to accomplish this at 20% of the dose of the PS-DNA,
      and in contrast to the PS-AS DNA, their silencing effect was still present after
      4 days after a single administration. Therefore, our data demonstrate that PS-2'F
      ANA-DNA chimeras are efficient gene silencing molecules, and suggest that they
      could have significant therapeutic potential.

PMID- 16421273
TI  - Molecular characterization of geminivirus-derived small RNAs in different plant
      species.
AB  - DNA geminiviruses are thought to be targets of RNA silencing. Here, we
      characterize small interfering (si) RNAs-the hallmarks of silencing-associated
      with Cabbage leaf curl begomovirus in Arabidopsis and African cassava mosaic
      begomovirus in Nicotiana benthamiana and cassava. We detected 21, 22 and 24 nt
      siRNAs of both polarities, derived from both the coding and the intergenic
      regions of these geminiviruses. Genetic evidence showed that all the 24 nt and a
      substantial fraction of the 22 nt viral siRNAs are generated by the dicer-like
      proteins DCL3 and DCL2, respectively. The viral siRNAs were 5' end
      phosphorylated, as shown by phosphatase treatments, and methylated at the 3'
      nucleotide, as shown by HEN1 miRNA methylase-dependent resistance to beta
      elimination. Similar modifications were found in all types of endogenous and
      transgene-derived siRNAs tested, but not in a major fraction of siRNAs from a
      cytoplasmic RNA tobamovirus. We conclude that several distinct silencing pathways
      are involved in DNA virus-plant interactions.

PMID- 16421274
TI  - Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA.
AB  - The present study shows that arsenic induces GADD45alpha (growth arrest and DNA
      damage inducible gene 45alpha) mainly through post-transcriptional mechanism.
      Treatment of the human bronchial epithelial cell line, BEAS-2B, with arsenic(III)
      chloride (As3+) resulted in a significant increase in GADD45alpha protein and
      mRNA. However, As3+ only exhibited a marginal effect on the transcription of the
      GADD45alpha gene. The accumulation of GADD45alpha mRNA is largely achieved by the
      stabilization of GADD45alpha mRNA in the cellular response to As3+. As3+ is able
      to induce binding of mRNA stabilizing proteins, nucleolin and less potently, HuR,
      to the GADD45alpha mRNA. Although As3+ was unable to affect the expression of
      nucleolin, treatment of the cells with As3+ resulted in re-distribution of
      nucleolin from nucleoli to nucleoplasm. Silencing of the nucleolin mRNA by RNA
      interference reversed As3+-induced stabilization of the GADD45alpha mRNA and
      accumulation of the GADD45alpha protein. Stabilization of GADD45alpha mRNA, thus,
      represents a novel mechanism contributing to the production of GADD45alpha and
      cell cycle arrest in response to As3+.

PMID- 16421275
TI  - Dual degradation signals control Gli protein stability and tumor formation.
AB  - Regulated protein destruction controls many key cellular processes with aberrant
      regulation increasingly found during carcinogenesis. Gli proteins mediate the
      transcriptional effects of the Sonic hedgehog pathway, which is implicated in up
      to 25% of human tumors. Here we show that Gli is rapidly destroyed by the
      proteasome and that mouse basal cell carcinoma induction correlates with Gli
      protein accumulation. We identify two independent destruction signals in Gli1,
      D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and
      rapidly accelerates tumor formation in transgenic animals. These data argue that
      control of Gli protein accumulation underlies tumorigenesis and suggest a new
      avenue for antitumor therapy.

PMID- 16421277
TI  - Swings and roundabouts for muscle gain and loss: differences between sexes?

PMID- 16421276
TI  - Phosphorylation-dependent maturation of Neurospora circadian clock protein from a
      nuclear repressor toward a cytoplasmic activator.
AB  - Frequency (FRQ) is a central component of interconnected negative and positive
      limbs of feedback loops of the circadian clock of Neurospora. In the negative
      limb, FRQ inhibits its transcriptional activator White Collar Complex (WCC) and
      in the positive limb, FRQ supports accumulation of WCC. We show that these
      conflicting functions are confined to distinct subcellular compartments and
      coordinated in temporal fashion. Inactivation of the transcriptional activator
      WCC requires nuclear FRQ and occurs early after the onset of FRQ expression.
      Support of WCC accumulation requires cytosolic FRQ and occurs on a post
      translational level, when high amounts of FRQ have accumulated. The
      transcriptional function of FRQ in the negative loop and its post-translational
      function in the positive loop are independent and associated with distinct
      regions of FRQ. Phosphorylation of FRQ at the PEST-2 region triggers its
      maturation from a nuclear repressor toward a cytoplasmic activator.

PMID- 16421278
TI  - Platelet count and function at high altitude and in high-altitude pulmonary
      edema.
AB  - Platelet aggregation is the key process in primary hemostasis. Certain conditions
      such as hypoxia may induce platelet aggregation and lead to platelet
      sequestration primarily in the pulmonary microcirculation. We investigated the
      influence of high-altitude exposure on platelet function as part of a larger
      study on 30 subjects with a history of high-altitude pulmonary edema (HAPE) and
      10 healthy controls. All participants were studied in the evening and the next
      morning at low altitude (450 m) and after an ascent to high altitude (4,559 m).
      Platelet count, platelet aggregation (platelet function analyzer PFA100; using
      epinephrine and ADP as activators), plasma soluble P (sP)-selectin, and the
      coagulation parameters prothrombin fragments 1+2 and thrombin-antithrombin
      complex were measured. High-altitude exposure decreased the platelet count,
      shortened the platelet function analyzer closure time by approximately 20%,
      indicating increased platelet aggregation, increased sP-selectin levels to
      approximately 250%, but left plasma coagulation unaffected. The HAPE-susceptible
      subjects were prophylactically treated with either tadalafil (a phosphodiesterase
      5 inhibitor), dexamethasone, or placebo in a double-blind way. Subgroup analyses
      between these different treatments and comparisons of the seven placebo-treated
      individuals developing HAPE and controls revealed no differences in platelet
      count, platelet aggregation, or sP-selectin values. We conclude that exposure to
      high altitude activates platelets, which leads to platelet aggregation, platelet
      consumption, and decreased platelet count. These effects are, however, not more
      pronounced in individuals with a history of HAPE or actually suffering from HAPE
      than in controls and therefore may not be a pathophysiological mechanism of HAPE.

PMID- 16421279
TI  - Chronic hypoxia and the cerebral circulation.
AB  - Exposure to mild hypoxia elicits a characteristic cerebrovascular response in
      mammals, including humans. Initially, cerebral blood flow (CBF) increases as much
      as twofold. The blood flow increase is blunted somewhat by a decreasing arterial
      Pco2 as a result of the hypoxia-induced hyperventilatory response. After a few
      days, CBF begins to fall back toward baseline levels as the blood oxygen-carrying
      capacity is increasing due to increasing hemoglobin concentration and packed red
      cell volume as a result of erythropoietin upregulation. By the end of 2 wk of
      hypoxic exposure, brain capillary density has increased with resultant decreased
      intercapillary distances. The relative time courses of these changes suggest that
      they are adjusted by different control signals and mechanisms. The CBF response
      appears linked to the blood oxygen-carrying capacity, whereas the hypoxia-induced
      brain angiogenesis appears to be in response to tissue hypoxia.

PMID- 16421280
TI  - Hypoxic regulation of the fetal cerebral circulation.
AB  - Fetal cerebrovascular responses to acute hypoxia are fundamentally different from
      those observed in the adult cerebral circulation. The magnitude of hypoxic
      vasodilatation in the fetal brain increases with postnatal age although fetal
      cerebrovascular responses to acute hypoxia can be complicated by age-dependent
      depressions of blood pressure and ventilation. Acute hypoxia promotes adenosine
      release, which depresses fetal cerebral oxygen consumption through action of
      adenosine on neuronal A1 receptors and vasodilatation through activation of A2
      receptors on cerebral arteries. The vascular effect of adenosine can account for
      approximately half the vasodilatation observed in response to hypoxia. Hypoxia
      induced release of nitric oxide and opioids can account for much of the adenosine
      independent cerebral vasodilatation observed in response to hypoxia in the fetus.
      Direct effects of hypoxia on cerebral arteries account for the remaining
      fraction, although the vascular endothelium contributes relatively little to
      hypoxic vasodilatation in the immature cerebral circulation. In contrast to acute
      hypoxia, fetal cerebral blood flow tends to normalize during acclimatization to
      chronic hypoxia even though cardiac output is depressed. However, uncompensated
      chronic hypoxia in the fetus can produce significant changes in brain structure
      and function, alteration of respiratory drive and fluid balance, and increased
      incidence of intracranial hemorrhage and periventricular leukomalacia. At the
      level of the fetal cerebral arteries, chronic hypoxia increases protein content
      and depresses norepinephrine release, contractility, and receptor densities
      associated with contraction but also attenuates endothelial vasodilator capacity
      and decreases the ability of ATP-sensitive and calcium-sensitive potassium
      channels to promote vasorelaxation. Overall, fetal cerebrovascular adaptations to
      chronic hypoxia appear prioritized to conserve energy while preserving basic
      contractility. Many gaps remain in our understanding of how the effects of acute
      and chronic hypoxia are mediated in fetal cerebral arteries, but studies of adult
      cerebral arteries have produced many powerful pharmacological and molecular tools
      that are simply awaiting application in studies of fetal cerebral artery
      responses to hypoxia.

PMID- 16421281
TI  - Reactive oxygen species: influence on cerebral vascular tone.
AB  - Reactive oxygen species have multiple effects on vascular cells. Defining the
      sources and the impact of the various reactive oxygen species within the vessel
      wall has emerged as a major area of study in vascular biology. This review will
      focus on recent findings related to effects of reactive oxygen species on
      cerebral vascular tone. Effects of superoxide radical, hydrogen peroxide, and the
      reactive nitrogen species peroxynitrite are summarized. Although higher
      concentrations may be important for cerebral vascular biology in disease,
      relatively low concentrations of reactive oxygen species may function as
      signaling molecules involved with normal regulation of cerebral vascular tone.
      The mechanisms by which reactive oxygen species affect vascular tone may be quite
      complex, and our understanding of these processes is increasing. Additionally,
      the role of reactive oxygen species as mediators of endothelium-dependent
      relaxation is addressed. Finally, the consequences of the molecular interactions
      of superoxide with nitric oxide and arachidonic acid are discussed.

PMID- 16421282
TI  - Point: in health and in a normoxic environment, VO2 max is limited primarily by
      cardiac output and locomotor muscle blood flow.

PMID- 16421283
TI  - Comment on Point:Counterpoint "positive effects of intermittent hypoxia (live
      high:train low) on exercise performance are/are not mediated primarily by
      augmented red cell volume".

PMID- 16421284
TI  - Comment on Point:Counterpoint "The muscle metaboreflex does/does not restore
      blood flow to contracting muscles".

PMID- 16421285
TI  - beta(2)-Adrenergic stimulation attenuates left ventricular remodeling, decreases
      apoptosis, and improves calcium homeostasis in a rodent model of ischemic
      cardiomyopathy.
AB  - The benefit of the beta(2)-adrenergic agonist, clenbuterol, in left ventricular
      assist device patients with dilated cardiomyopathy has been reported, but its
      effect on ischemic heart failure (HF) is unknown. We investigated whether
      clenbuterol improves left ventricular remodeling, myocardial apoptosis and has
      synergy with a beta(1) antagonist, metoprolol, in a model of ischemic HF. Rats
      were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF +
      clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left
      anterior descending artery (LAD) artery ligation and confirmed by decreased left
      ventricular fractional shortening, decreased maximum left ventricular dP/dt
      (dP/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP)
      compared with sham rats (p < 0.01). After 9 weeks of oral therapy,
      echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume
      relationship (EDPVR) measurements were obtained. Immunohistochemistry was
      performed for myocardial apoptosis and DNA damage markers. Levels of calcium
      handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF
      rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR
      curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF
      rats (p < 0.05). The metoprolol-treated group had a lower LVEDP and higher
      dP/dt(max) versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had
      decreased myocardial apoptosis and DNA damage markers and increased DNA repair
      markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor
      and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-,
      metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However,
      as a combination therapy, there were no synergistic effects of
      clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR,
      apoptosis, and calcium homeostasis but does not have synergy with metoprolol in
      our model of ischemic HF.

PMID- 16421286
TI  - Characterization of mice lacking the multidrug resistance protein MRP2 (ABCC2).
AB  - The multidrug resistance protein Mrp2 is an ATP-binding cassette (ABC)
      transporter mainly expressed in liver, kidney, and intestine. One of the
      physiological roles of Mrp2 is to transport bilirubin glucuronides from the liver
      into the bile. Current in vivo models to study Mrp2 are the transporter-deficient
      and Eisai hyperbilirubinemic rat strains. Previous reports showed
      hyperbilirubinemia and induction of Mrp3 in the hepatocyte sinusoidal membrane in
      the mutant rats. In addition, differences in liver cytochrome P450 and UGT1a
      levels between wild-type and mutant rats were detected. To study whether these
      compensatory mechanisms were specific to rats, we characterized Mrp2(-/-) mice.
      Functional absence of Mrp2 in the knockout mice was demonstrated by showing
      increased levels of bilirubin and bilirubin glucuronides in serum and urine, a
      reduction in biliary excretion of bilirubin glucuronides and total glutathione,
      and a reduction in the biliary excretion of the Mrp2 substrate
      dibromosulfophthalein. To identify possible compensatory mechanisms in Mrp2(-/-)
      mice, the expression levels of 98 phase I, phase II, and transporter genes were
      compared in liver, kidney, and intestine of male and female Mrp2(-/-) and control
      mice. Unlike in Mrp2 mutant rats, no induction of Mrp3 in Mrp2(-/-) mice was
      detected. However, Mrp4 mRNA and protein in liver and kidney were increased
      approximately 6- and 2-fold, respectively. Phenotypic analysis of major
      cytochrome P450-mediated activities in liver microsomes did not show differences
      between wild-type and Mrp2(-/-) mice. In conclusion, Mrp2(-/-) mice are a new
      valuable tool to study the role of Mrp2 in drug disposition.

PMID- 16421287
TI  - Induction of renal cytochrome P450 arachidonic acid epoxygenase activity by
      dietary gamma-linolenic acid.
AB  - Dietary gamma-linolenic acid (GLA), a omega-6 polyunsaturated fatty acid found in
      borage oil (BOR), lowers systolic blood pressure in spontaneously hypertensive
      rats (SHRs). GLA is converted into arachidonic acid (AA) by elongation and
      desaturation steps. Epoxyeicosatrienoic acids (EETs) and 20
      hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 (P450)-derived AA
      eicosanoids with important roles in regulating blood pressure. This study tested
      the hypothesis that the blood pressure-lowering effect of a GLA-enriched diet
      involves alteration of P450-catalyzed AA metabolism. Microsomes and RNA were
      isolated from the renal cortex of male SHRs fed a basal fat-free diet for 5 weeks
      to which 11% by weight of sesame oil (SES) or BOR was added. There was a 2.6- to
      3.5-fold increase in P450 epoxygenase activity in renal microsomes isolated from
      the BOR-fed SHRs compared with the SES-fed rats. Epoxygenase activity accounted
      for 58% of the total AA metabolism in the BOR-treated kidney microsomes compared
      with 33% in the SES-treated rats. More importantly, renal 14,15- and 8,9-EET
      levels increased 1.6- to 2.5-fold after dietary BOR treatment. The increase in
      EET formation is consistent with increases in CYP2C23, CYP2C11, and CYP2J protein
      levels. There were no differences in the level of renal P450 epoxygenase mRNA
      between the SES- and BOR-treated rats. Enhanced synthesis of the vasodilatory
      EETs and decreased formation of the vasoconstrictive 20-HETE suggests that
      changes in P450-mediated AA metabolism may contribute, at least in part, to the
      blood pressure-lowering effect of a BOR-enriched diet.

PMID- 16421288
TI  - Phenobarbital treatment inhibits the formation of estradiol-dependent mammary
      tumors in the August-Copenhagen Irish rat.
AB  - Exposure of female August-Copenhagen Irish (ACI) rats for 28 weeks to 3 mg of
      estradiol (E(2)) contained in cholesterol pellets elevated blood E(2) levels and
      caused palpable mammary tumors in all animals. Coadministration of phenobarbital
      (PB) in their drinking water reduced the incidence, number, and size of mammary
      tumors (MTs) but did not reduce blood E(2) levels. Inhibition of MTs by PB was
      accompanied by significant changes in total hepatic metabolism of E(2) measured
      in vitro. PB treatment caused approximately a 4-fold increase in hepatic
      metabolism of E(2) in control and E(2)-treated rats. The major NAD(P)H-dependent
      metabolites of E(2) were 2-OH-E(2) and estrone (E(1)). PB, either alone or
      together with E(2), increased microsomal 2-hydroxylation of E(2); formation of
      E(1) was either unaffected or decreased slightly. PB also increased microsomal
      metabolism of E(2) to minor metabolites (4-OH-E(2), 6alpha-OH-E(2), 6beta-OH
      E(2), 14alpha-OH-E(2), 6-keto E(1), and 2-OH-E(1)) and reduced the formation of
      the E(2)-17beta-oleoyl ester and the E(2) 3- and 17-glucuronides. In contrast,
      when given in combination with E(2), PB increased the formation of both
      glucuronides. Cotreatment of animals with PB and E(2) increased activities of
      NAD(P)H:quinone oxidoreductase and glutathione S-transferase to a greater extent
      than either compound alone. Collectively, these results show that the multiple
      actions of PB on hepatic metabolism of E(2), including induction of E(2)
      hydroxylation, glucuronidation, and antioxidant defense enzymes along with
      inhibition of E(2) esterification in livers of female ACI rats, accompany a
      marked reduction of E(2)-dependent mammary tumors in this model.

PMID- 16421289
TI  - Adenosine receptors find a new partner and move out.
AB  - Recent studies of G protein-coupled receptors have highlighted two "new" and
      interactive elements involved in their function and regulation: their ability to
      localize to different cell surface and intracellular compartments and their
      ability to interact with partners other than their classic heterotrimeric G
      proteins. The effects mediated by these receptors can be markedly different
      depending on the compartment in which they reside and the partners with which
      they interact in each compartment. The studies in this issue of Molecular
      Pharmacology by Milojevic et al. (page 1083) merge these two themes by
      identifying the ubiquitin-specific protease Usp4 as a partner for the carboxyl
      terminal tail of adenosine A2A receptors and showing that this interaction allows
      processing and delivery to the cell surface of newly synthesized A2A receptors,
      which are otherwise predominantly intracellular. Their studies suggest that the
      intracellular A2A receptors are ubiquitinated, presumably because of misfolding
      and intervention of the "endoplasmic reticulum quality control" mechanism leading
      to degradation of the receptors by proteasomes. Increasing Usp4 expression
      stimulates receptor de-ubiquitination and increases cell surface expression of
      functional receptors. Evidence is presented for tight specificity of this
      interaction, with another Usp family member failing to rescue A2A receptors and
      Usp4 failing to rescue another intracellular receptor. The background and
      significance of this study are highlighted here, including puzzles that remain to
      be solved and the potential for pharmacological targeting of such interactions to
      manipulate the expression, location, and function of G protein-coupled receptors
      for therapeutic benefit.

PMID- 16421290
TI  - The anti-yellow fever virus activity of ribavirin is independent of error-prone
      replication.
AB  - The precise mechanism by which the broad-spectrum anti-RNA virus agent ribavirin
      elicits its in vitro antiviral effect has remained a matter of debate. We have
      demonstrated that inhibition of cellular inosine monophosphate dehydrogenase
      (IMPDH) activity, and thus depletion of intracellular GTP pools, is the
      predominant mechanism by which ribavirin inhibits the replication of four flavi-
      and two paramyxoviruses (J Virol 79:1943-1947, 2005). As a consequence, induction
      of error catastrophe, which has been proposed as a mechanism by which ribavirin
      may elicit its anti-RNA virus activity, may be expected to have little, if any,
      impact on its antiviral effect. The flavivirus yellow fever virus (17D vaccine
      strain) was cultured for five consecutive passages in the presence of 1-beta-D
      ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 5-ethynyl-1-beta-D-ribo
      furanosylimidazole-4-carboxamide (EICAR) (the 5-ethynyl analog of ribavirin), or
      mycophenolic acid (MPA; a compound that exclusively inhibits IMPDH). The
      reduction in infectious virus yield brought about by ribavirin (as well as MPA
      and EICAR) was paralleled by a similar reduction in viral RNA yield; in case of
      error-prone replication, the infectious virus yield is expected to decrease
      significantly faster than the viral RNA yield. In addition, pre-extinction
      populations of the virus that has suffered a maximum impact of treatment with
      ribavirin did not accumulate an increased number of mutations. Very similar
      observations were obtained with EICAR and with MPA, a molecule that cannot be
      incorporated into viral RNA. These data thus allow us to conclude that the in
      vitro anti-yellow fever virus activity of ribavirin is independent of error-prone
      replication.

PMID- 16421291
TI  - Inhibition of cardiac hypertrophy by triflusal (4-trifluoromethyl derivative of
      salicylate) and its active metabolite.
AB  - The nuclear factor (NF)-kappaB signaling pathway is an important intracellular
      mediator of cardiac hypertrophy. The aim of the present study was to determine
      whether triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), a salicylate
      derivative used as antiplatelet agent, and its active metabolite 2-hydroxy-4
      trifluoromethylbenzoic acid (HTB) inhibit cardiac hypertrophy in vitro and in
      vivo by blocking the NF-kappaB signaling pathway. In cultured neonatal rat
      cardiomyocytes, HTB (300 microM, a concentration reached in clinical use)
      inhibited phenylephrine (PE)-induced protein synthesis ([3H]leucine uptake),
      induction of the fetal-type gene atrial natriuretic factor (ANF), and sarcomeric
      disorganization. Assessment of the effects of triflusal in pressure overload
      induced cardiac hypertrophy by aortic banding resulted in a significant reduction
      in the ratio of heart weight to body weight and in a reduction of the mRNA levels
      of the cardiac hypertrophy markers ANF and alpha-actinin compared with untreated
      banded rats. Electrophoretic mobility shift assay revealed an increase in the NF
      kappaB binding activity in cardiac nuclear extracts of banded rats that was
      prevented by triflusal treatment. It is noteworthy that banded rats treated with
      oral triflusal, compared with untreated rats, showed enhanced protein levels of
      IkappaBalpha, which forms a cytoplasmic inactive complex with the p65-p50
      heterodimeric complex. Finally, HTB increased phospho-IkappaBalpha levels in
      neonatal cardiomyocytes and inhibited proteosome activity, suggesting that this
      drug prevented proteosome-mediated degradation of IkappaBalpha. These results
      indicate that triflusal, a drug with a well characterized pharmacological and
      safety profile currently used as antiplatelet, inhibits cardiomyocyte growth by
      interfering with the NF-kappaB signaling pathway through a post-transcriptional
      mechanism involving reduced-proteosome degradation of IkappaBalpha.

PMID- 16421292
TI  - Primary reinforcing effects of nicotine are triggered from multiple regions both
      inside and outside the ventral tegmental area.
AB  - Nicotine is thought to be the key substance responsible for tobacco-smoking
      habits and appears to trigger reinforcement via the ventral tegmental area (VTA).
      Recently, multiple anatomical substrates for drug reinforcement have been
      identified in the vicinity of the ventral midbrain. In addition to the posterior
      portion of the VTA, the central linear nucleus raphe and the supramammillary
      nucleus of the posterior hypothalamus mediate drug reinforcement. Using
      intracranial self-administration procedures, we examined whether these regions
      mediate the reinforcing effects of nicotine. Rats learned to lever press for self
      administration of nicotine into the posterior VTA, central linear nucleus, and
      supramammillary nucleus, suggesting a reinforcing action of nicotine in these
      regions. The rats did not self-administer nicotine into surrounding regions
      including the anterior VTA, substantia nigra, the region just dorsal to the
      posterior VTA, interpeduncular nucleus, or medial mammillary nucleus. The
      reinforcing effects of nicotine into the three brain regions were further
      confirmed by a two-lever discrimination procedure, in which rats learned to
      selectively respond between active and inactive levers. The reinforcing effects
      of nicotine administration into the posterior VTA, central linear nucleus, and
      supramammillary nucleus were blocked by coadministration of the nicotine receptor
      antagonist mecamylamine. The reinforcing effects of nicotine into the posterior
      VTA or central linear nucleus were attenuated by coadministration of the D2
      receptor agonist quinpirole. These findings demonstrate that nicotine
      reinforcement involves multiple regions both inside and outside the VTA.

PMID- 16421293
TI  - Traumatic injury and the presence of antigen differentially contribute to T-cell
      recruitment in the CNS.
AB  - T-cell recruitment into the brain is critical in inflammatory and autoimmune
      diseases of the CNS. We use intracerebral antigen microinjection and tetramer
      technology to track antigen-specific CD8+ T-cells in the CNS and to clarify the
      contribution of antigen deposition or traumatic injury to the accumulation of T
      cells in the brain. We demonstrate that, after intracerebral microinjection of
      ovalbumin, ovalbumin-specific CD8+ T-cells expand systemically and then migrate
      into the brain where they complete additional proliferation cycles. T-cells in
      the brain are activated and respond to in vitro secondary antigen challenge. CD8+
      T-cells accumulate and persist in sites of antigen in the brain without
      replenishment from the periphery. Persistent survival of CD8+ T-cells at sites of
      cognate antigen is significantly reduced by blocking CD154 molecules. A small
      traumatic injury itself does not lead to recruitment of CD8+ T-cells into the
      brain but attracts activated antigen-specific CD8+ T-cells from cognate antigen
      injection sites. This process is presumably antigen independent and cannot be
      inhibited by blocking CD154 molecules. These data show that activated antigen
      specific CD8+ T-cells accumulate in the CNS at both cognate antigen-containing
      and traumatic injury sites after intracerebral antigen delivery. The accumulation
      of activated antigen-specific T-cells at traumatic injury sites, in addition to
      antigen-containing areas, could amplify local inflammatory processes in the CNS.
      Combination therapies in neuroinflammatory diseases to block both of these
      processes should be considered.

PMID- 16421294
TI  - Reversal of neuronal migration in a mouse model of fetal alcohol syndrome by
      controlling second-messenger signalings.
AB  - The brains of fetal alcohol syndrome patients exhibit impaired neuronal
      migration, but little is known about the mechanisms underlying this abnormality.
      Here we show that Ca2+ signaling and cyclic nucleotide signaling are the central
      targets of alcohol action in neuronal cell migration. Acute administration of
      ethanol reduced the frequency of transient Ca2+ elevations in migrating neurons
      and cGMP levels and increased cAMP levels. Experimental manipulations of these
      second-messenger pathways, through stimulating Ca2+ and cGMP signaling or
      inhibiting cAMP signaling, completely reversed the action of ethanol on neuronal
      migration in vitro as well as in vivo. Each second messenger has multiple but
      distinct downstream targets, including Ca2+/calmodulin-dependent protein kinase
      II, calcineurin, protein phosphatase 1, Rho GTPase, mitogen-activated protein
      kinase, and phosphoinositide 3-kinase. These results demonstrate that the
      aberrant migration of immature neurons in the fetal brain caused by maternal
      alcohol consumption may be corrected by controlling the activity of these second
      messenger pathways.

PMID- 16421295
TI  - Ermin, a myelinating oligodendrocyte-specific protein that regulates cell
      morphology.
AB  - Oligodendrocytes form an insulating multilamellar structure of compact myelin
      around axons, thereby allowing rapid propagation of action potentials. Despite
      the considerable clinical importance of myelination, little is known about the
      molecular mechanisms that enable oligodendrocytes to generate their specialized
      membrane wrapping. Here, we used microarray expression profiling of
      oligodendrocyte-ablated mutant mice to identify new glial molecules that are
      involved in CNS myelination. This effort resulted in the identification of Ermin,
      a novel cytoskeletal molecule that is exclusively expressed by oligodendrocytes.
      Ermin appears at a late stage during myelination, and in the mature nerves, it is
      localized to the outer cytoplasmic lip of the myelin sheath and the paranodal
      loops. In cultured oligodendrocytes, Ermin becomes visible in well differentiated
      MBP-positive cells, where it is concentrated at the tip of F-actin-rich processes
      (termed "Ermin spikes"). Ectopic expression of Ermin, but not of a mutant protein
      lacking its actin-binding domain, induced the formation of numerous cell
      protrusions and a pronounced change in cell morphology. Our results demonstrate
      that Ermin is a novel marker of myelinating oligodendroglia and suggest that it
      plays a role in cytoskeletal rearrangements during the late wrapping and/or
      compaction phases of myelinogenesis.

PMID- 16421296
TI  - Essential contribution of the ligand-binding beta B/beta C loop of PDZ1 and PDZ2
      in the regulation of postsynaptic clustering, scaffolding, and localization of
      postsynaptic density-95.
AB  - Postsynaptic density-95 (PSD-95), a PSD-95/Discs large/zona occludens-1 (PDZ)
      domain-containing scaffold protein, clusters many signaling molecules near NMDA
      type glutamate receptors in the postsynaptic densities. Although the synaptic
      localization of PSD-95 requires palmitoylation of two cysteines at the N terminus
      and the presence of at least one PDZ domain, how the clustering of PSD-95 is
      initiated and regulated remains essentially unknown. To address this issue, we
      examined PSD-95 clustering in primary cultured hippocampal neurons expressing
      full-length PSD-95 mutant proteins lacking the ligand-binding ability of PDZ1,
      PDZ2, and/or PDZ3. The formation of either excitatory or inhibitory synapses was
      unaffected. Combinations of individual mutations, however, significantly reduced
      the PSD-95 clustering index, in an approximately additive manner. The sensitivity
      to 2-bromo-palmitate and latrunculin A, reagents known to affect PSD-95 turnover,
      was also augmented. Furthermore, the synaptic recruitment of a PSD-95 ligand,
      synaptic GTPase-activating protein (synGAP), was significantly impaired, whereas
      the clustering of other scaffolding proteins, such as Homer 1c, Shank/Synamon,
      and PSD-93/Chapsin-110 was spared. Intriguingly, overexpression of the PSD-95
      PDZ1/2/3 mutants caused the PSD-95 clusters to localize away from the dendritic
      shaft, resulting in the formation of elongated spines, in an inverse correlation
      with the overall PDZ-ligand affinity. Expression of a mutant synGAP lacking the
      PDZ-binding motif replicated both the clustering and spine morphology phenotypes.
      In conclusion, the ligand-binding affinity of the PDZ domains of PSD-95,
      contributed in part via its interaction with the C-terminal end of synGAP, plays
      a critical role in titrating the synaptic clustering of PSD-95 and controlling
      its tight association with the PSD scaffold, thereby affecting synapse
      maturation.

PMID- 16421297
TI  - Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor
      protein transgenic mouse models.
AB  - Nerve cells that re-enter a cell cycle will die rather than divide, a fact that
      likely underlies the neurodegeneration in Alzheimer's disease (AD). Several mouse
      models of familial AD have been created, and although many display amyloid
      plaques in their brains, none captures the extensive pattern of nerve cell death
      found in the human disease. Using both immunocytochemistry and fluorescent in
      situ hybridization, we show that neurons in three different mouse models
      reproduce the ectopic cell cycling found in human AD. The temporal and spatial
      appearance of the cell cycle events in the mouse closely mimics the human disease
      progression. The cell-cycle events are evident 6 months before the first amyloid
      deposits and significantly precede the appearance of the first CD45+ microglia.
      These data suggest that the ectopic initiation of cell-cycle processes in neurons
      is an early sign of neuronal distress in both human and mouse AD. The close
      phenotypic correspondence indicates a previously unsuspected level of fidelity of
      the mouse model to the human disease. Finally, the relative timing suggests that
      neither the activated microglia nor the amyloid plaques themselves are necessary
      to initiate the pathogenic events in AD.

PMID- 16421298
TI  - A neural correlate of stochastic echo imaging.
AB  - Bats quickly navigate through a highly structured environment relying on
      echolocation. Large natural objects in the environment, like bushes or trees,
      produce complex stochastic echoes, which can be characterized by the echo
      roughness. Previous work has shown that bats can use echo roughness to classify
      the stochastic properties of natural objects. This study provides both
      psychophysical and electrophysiological data to identify a neural correlate of
      statistical echo analysis in the bat Phyllostomus discolor. Psychophysical
      results show that the bats require a fixed minimum roughness of 2.5 (in units of
      base 10 logarithm of the stimulus fourth moment) for roughness discrimination.
      Electrophysiological results reveal a subpopulation of 15 of 94 recorded cortical
      units, located in an anterior region of auditory cortex, whose rate responses
      changed significantly with echo roughness. It is shown that the behavioral
      ability to discriminate differences in the statistics of complex echoes can be
      quantitatively predicted by the neural responses of this subpopulation of
      auditory-cortical neurons.

PMID- 16421299
TI  - Neuroanatomical dissociation of encoding processes related to priming and
      explicit memory.
AB  - Priming is a facilitation of cognitive processing with stimulus repetition that
      can occur without explicit memory. Whereas the functional neuroanatomy of
      perceptual priming at retrieval is established, encoding processes that initiate
      priming and explicit memory have not yet been anatomically separated, and we
      investigated them using event-related functional magnetic resonance imaging.
      Activations predicting later explicit memory occurred in the bilateral medial
      temporal lobe (MTL) and left prefrontal cortex (PFC). Activity predicting later
      priming did not occur in these areas, but rather in the bilateral extrastriate
      cortex, left fusiform gyrus, and bilateral inferior PFC, areas linked with
      stimulus identification. Surprisingly, these regions showed response reductions.
      Our results demonstrate that priming and explicit memory have distinct functional
      neuroanatomies at encoding, with MTL activations being specific for explicit
      memory, and suggest that priming is initiated by sharpness of neural responding
      in stimulus identification areas, consistent with recent electrophysiological
      evidence regarding priming-related neural oscillations at encoding. We
      tentatively suggest that this sharpened responding at encoding may set the stage
      for increased neural processing efficiency at retrieval, with these different
      neural mechanisms both leading to observed priming-related hemodynamic decreases,
      and argue that neural measurements at encoding, and not just at retrieval, will
      be critical in resolving the debate about the neural mechanisms of learning that
      underlie priming.

PMID- 16421300
TI  - Spike count reliability and the Poisson hypothesis.
AB  - The variability of cortical activity in response to repeated presentations of a
      stimulus has been an area of controversy in the ongoing debate regarding the
      evidence for fine temporal structure in nervous system activity. We present a new
      statistical technique for assessing the significance of observed variability in
      the neural spike counts with respect to a minimal Poisson hypothesis, which
      avoids the conventional but troubling assumption that the spiking process is
      identically distributed across trials. We apply the method to recordings of
      inferotemporal cortical neurons of primates presented with complex visual
      stimuli. On this data, the minimal Poisson hypothesis is rejected: the neuronal
      responses are too reliable to be fit by a typical firing-rate model, even
      allowing for sudden, time-varying, and trial-dependent rate changes after
      stimulus onset. The statistical evidence favors a tightly regulated stimulus
      response in these neurons, close to stimulus onset, although not further away.

PMID- 16421301
TI  - Mitochondrial encephalomyopathy in Drosophila.
AB  - Mitochondrial encephalomyopathies are common and devastating multisystem genetic
      disorders characterized by neuromuscular dysfunction and tissue degeneration.
      Point mutations in the human mitochondrial ATP6 gene are known to cause several
      related mitochondrial disorders: NARP (neuropathy, ataxia, and retinitis
      pigmentosa), MILS (maternally inherited Leigh's syndrome), and FBSN (familial
      bilateral striatal necrosis). We identified a pathogenic mutation in the
      Drosophila mitochondrial ATP6 gene that causes progressive, adult-onset
      neuromuscular dysfunction and myodegeneration. Our results demonstrate
      ultrastructural defects in the mitochondrial innermembrane, neural dysfunction,
      and a marked reduction in mitochondrial ATP synthase activity associated with
      this mutation. This Drosophila mutant recapitulates key features of the human
      neuromuscular disorders enabling detailed in vivo studies of these enigmatic
      diseases.

PMID- 16421302
TI  - Mental chronometry of working memory retrieval: a combined functional magnetic
      resonance imaging and event-related potentials approach.
AB  - We used the combination of functional magnetic resonance imaging and event
      related potentials to decompose the processing stages (mental chronometry) of
      working memory retrieval. Our results reveal an early transient activation of
      inferotemporal cortex, which was accompanied by the onset of a sustained
      activation of posterior parietal cortex. We furthermore observed late transient
      responses in ventrolateral prefrontal cortex and late sustained activity in
      medial frontal and premotor areas. We propose that these neural signatures
      reflect the cognitive stages of task processing, perceptual evaluation
      (inferotemporal cortex), storage buffer operations (posterior parietal cortex),
      active retrieval (ventrolateral prefrontal cortex), and action selection (medial
      frontal and premotor cortex). This is also supported by their differential
      temporal contribution to specific subcomponents of the P300 cognitive potential.

PMID- 16421304
TI  - Selective attenuation of afferent synaptic transmission as a mechanism of
      thalamic deep brain stimulation-induced tremor arrest.
AB  - Deep brain stimulation (DBS) of the ventrolateral thalamus stops several forms of
      tremor. Microelectrode recordings in the human thalamus have revealed tremor
      cells that fire synchronous with electromyographic tremor. The efficacy of DBS
      likely depends on its ability to modify the activity of these tremor cells either
      synaptically by stopping afferent tremor signals or by directly altering the
      intrinsic membrane currents of the neurons. To test these possibilities, whole
      cell patch-clamp recordings of ventral thalamic neurons were obtained from rat
      brain slices. DBS was simulated (sDBS) using extracellular constant current pulse
      trains (125 Hz, 60-80 micros, 0.25-5 mA, 1-30 s) applied through a bipolar
      electrode. Using a paired-pulse protocol, we first established that
      thalamocortical relay neurons receive converging input from multiple independent
      afferent fibers. Second, although sDBS induced homosynaptic depression of EPSPs
      along its own pathway, it did not alter the response from a second independent
      pathway. Third, in contrast to the subthalamic nucleus, sDBS in the thalamus
      failed to inhibit the rebound potential and the persistent Na+ current but did
      activate the Ih current. Finally, in eight patients undergoing thalamic DBS
      surgery for essential tremor, microstimulation was most effective in alleviating
      tremor when applied in close proximity to recorded tremor cells. However,
      stimulation could still suppress tremor at distances incapable of directly
      spreading to recorded tremor cells. These complementary data indicate that DBS
      may induce a "functional deafferentation" of afferent axons to thalamic tremor
      cells, thereby preventing tremor signal propagation in humans.

PMID- 16421303
TI  - Critical role of integrin-linked kinase in granule cell precursor proliferation
      and cerebellar development.
AB  - Integrin-linked kinase (ILK) is a serine/threonine protein kinase that plays an
      important role in integrin signaling and cell proliferation. We used Cre
      recombinase (Cre)-loxP technology to study CNS restricted knock-out of the ilk
      gene by either Nestin-driven or gfap-driven Cre-mediated recombination.
      Developmental changes in ilk-excised brain regions are similar to those observed
      in mice lacking the integrin beta1 subunit in the CNS, including defective
      laminin deposition, abnormal glial morphology, and alterations in granule cell
      migration. Decreases in 6-bromodeoxyuridine (BrdU) pulse labeling and
      proliferating cell nuclear antigen expression in the external granule cell layer
      of the cerebellum demonstrated that proliferation is disrupted in granule cells
      lacking ILK. Previous studies have shown that laminin-sonic hedgehog (Shh)
      induced granule cell precursor (GCP) proliferation is dependent on beta1
      integrins, several of which bind laminin and interact with ILK through the beta1
      cytoplasmic domain. Both ex vivo deletion of ilk and a small molecule inhibitor
      of ILK kinase activity decreased laminin-Shh-induced BrdU labeling in cultured
      GCPs. Together, these results implicate ILK as a critical effector in a signaling
      pathway necessary for granule cell proliferation and cerebellar development.

PMID- 16421305
TI  - Calcium calmodulin-stimulated adenylyl cyclases contribute to activation of
      extracellular signal-regulated kinase in spinal dorsal horn neurons in adult rats
      and mice.
AB  - The extracellular signal-regulated kinase (Erk) cascades are suggested to
      contribute to excitatory synaptic plasticity in the CNS, including the spinal
      cord dorsal horn. However, many of their upstream signaling pathways remain to be
      investigated. Here, we demonstrate that glutamate and substance P (SP), two
      principal mediators of sensory information between primary afferent fibers and
      the spinal cord, activate Erk in dorsal horn neurons of both adult rat and mouse
      spinal cord. In genetic knock-out mice of calcium calmodulin-stimulated adenylyl
      cyclase subtypes 1 (AC1) and 8 (AC8), activation of Erk in dorsal horn neurons
      were significantly reduced or blocked, either after peripheral tissue
      inflammation or by glutamate or SP in spinal cord slices. Our studies suggest
      that AC1 and AC8 act upstream from Erk activation in spinal dorsal horn neurons
      and the calcium-AC1/AC8-dependent Erk signaling pathways may contribute to spinal
      sensitization, an underlying mechanism for the development of persistent pain
      after injury.

PMID- 16421306
TI  - Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction of
      exuberant retinal axons.
AB  - The calcium-stimulated adenylate cyclase 1 (AC1) has been shown to be required
      for the refinement of the retinotopic map, but the mechanisms involved are not
      known. To investigate this question, we devised a retinotectal coculture
      preparation that reproduces the gradual acquisition of topographic specificity
      along the rostrocaudal axis of the superior colliculus (SC). Temporal retinal
      axons invade the entire SC at 4 d in vitro (DIV) and eliminate exuberant branches
      caudally by 12 DIV. Temporal and nasal axons form branches preferentially in the
      rostral or caudal SC, respectively. Retinal explants from AC1-deficient mice,
      AC1(brl/brl), maintain exuberant branches and lose the regional selectivity of
      branching when confronted with wild-type (WT) SC. Conversely, WT retinas
      correctly target AC1(brl/brl) collicular explants. The effects of AC1 loss of
      function in the retina are mimicked by the blockade of ephrin-A5 signaling in WT
      cocultures. Video microscopic analyses show that AC1(brl/brl) axons have modified
      responses to ephrin-A5: the collapse of the growth cones occurs, but the rearward
      movement of the axon is arrested. Our results demonstrate a presynaptic, cell
      autonomous role of AC1 in the retina and further indicate that AC1 is necessary
      to enact a retraction response of the retinal axons to ephrin-A5 during the
      refinement of the retinotopic map.

PMID- 16421307
TI  - Hippocampus-mediated activation of superficial and deep layer neurons in the
      medial entorhinal cortex of the isolated guinea pig brain.
AB  - The entorhinal cortex (EC) is regarded as the structure that regulates
      information flow to and from the hippocampus. It is commonly assumed that
      superficial and deep EC neurons project to and receive from the hippocampal
      formation, respectively. Anatomical evidences suggest that both the hippocampal
      output and deep EC neurons also project to superficial EC layers. To functionally
      characterize the interlaminar synaptic EC circuit entrained the by hippocampal
      output, we performed simultaneous intracellular recordings and laminar profile
      analysis in the medial EC (m-EC) of the in vitro isolated guinea pig brain after
      polysynaptic hippocampal activation by lateral olfactory tract (LOT) stimulation.
      Optical imaging of voltage-generated signals confirmed that the LOT-evoked
      hippocampus-mediated response is restricted to the m-EC. The hippocampal output
      generated an extracellular current sink in layers V-VI, coupled with an EPSP in
      deep neurons. Deep neuron firing was terminated by a biphasic IPSP. The earliest
      response observed in superficial layer neurons was characterized by a feedforward
      IPSP of circa 100 ms (-69 +/- 1.3 mV reversal potential) abolished by local
      application of 1 mm bicuculline. The feedforward IPSP was followed by a delayed
      EPSP blocked by AP-5 (100 microM), presumably mediated by deep-to-superficial m
      EC connections. Our findings demonstrate that superficial m-EC cells are
      inhibited by the hippocampal output via a feedforward pathway that prevents
      activity reverberation in the hippocampal-EC-hippocampal loop. We propose that
      such inhibition could serve as a protective mechanism to prevent epileptic
      hyperexcitability.

PMID- 16421308
TI  - Multiple Eph receptors and B-class ephrins regulate midline crossing of corpus
      callosum fibers in the developing mouse forebrain.
AB  - Agenesis of the corpus callosum (CC) is a rare birth defect that occurs in
      isolated conditions and in combination with other developmental cerebral
      abnormalities. Recent identification of families of growth and guidance molecules
      has generated interest in the mechanisms that regulate callosal growth. One
      family, ephrins and Eph receptors, has been implicated in mediating midline
      pathfinding decisions; however, the complexity of these interactions has yet to
      be unraveled. Our studies shed light on which B-class ephrins and Eph receptors
      function to regulate CC midline growth and how these molecules interact with
      important guideposts during development. We show that multiple Eph receptors (B1,
      B2, B3, and A4) and B-class ephrins (B1, B2, and B3) are present and function in
      developing forebrain callosal fibers based on both spatial and temporal
      expression patterns and analysis of gene-targeted knock-out mice. Defects are
      most pronounced in the combination double knock-out mice, suggesting that
      compensatory mechanisms exist for several of these family members. Furthermore,
      these CC defects range from mild hypoplasia to complete agenesis and Probst's
      bundle formation. Further analysis revealed that Probst's bundle formation may
      reflect aberrant glial formations and/or altered sensitivity of CC axons to other
      guidance cues. Our results support a significant role for ephrins and Eph
      receptors in CC development and may provide insight to possible mechanisms
      involved in axon midline crossing and human disorder.

PMID- 16421309
TI  - Spatiotemporal structure of nonlinear subunits in macaque visual cortex.
AB  - The primate visual system is arranged hierarchically, starting from the retina
      and continuing through a series of extrastriate visual areas. Selectivity for
      motion is first found in individual neurons in the primate visual cortex (V1), in
      which many simple cells respond selectively to the direction and speed of moving
      stimuli. Beyond simple cells, most studies of direction selectivity have focused
      on either V1 complex cells or neurons in the middle temporal area (MT/V5). To
      understand how visual information is transferred along this pathway, we have
      studied all three types of neurons, using a reverse correlation procedure to
      obtain high spatial and temporal resolution maps of activity for different motion
      stimuli. Most complex and MT cells showed strong second-order interactions,
      indicating that they were tuned for particular displacements of an apparent
      motion stimulus. The spatiotemporal structure of these interactions showed a high
      degree of similarity between the populations of V1 complex cells and MT cells, in
      terms of the spatiotemporal limits and preferences for motion and their two
      dimensional spatial structure. Much of the structure in the V1 and MT second
      order kernels could be accounted for on the basis of the first-order responses of
      V1 simple cells, under the assumption of a Reichardt or motion-energy type of
      computation.

PMID- 16421311
TI  - Dorsolateral prefrontal cortex promotes long-term memory formation through its
      role in working memory organization.
AB  - Results from neuroimaging studies have shown that the dorsolateral prefrontal
      cortex (DLPFC) implements processes critical for organizing items in working
      memory (WM). Based on its role in WM, we hypothesized that the DLPFC should
      contribute to long-term memory (LTM) formation by strengthening associations
      among items that are organized in WM. We conducted an event-related functional
      magnetic resonance imaging (fMRI) study to test this hypothesis by investigating
      prefrontal activity during performance of two different WM tasks: on "rehearse"
      trials, participants actively maintained triplets of words during a brief delay,
      whereas on "reorder" trials, participants actively organized each triplet during
      the delay. After scanning, subjects performed an LTM test on words presented
      during both WM conditions. Behavioral results showed that WM processing in the
      reorder condition enhanced LTM by strengthening inter-item associations. fMRI
      results showed that DLPFC activity specifically during reorder trials was
      predictive of subsequent LTM. In contrast, activity in the posterior
      ventrolateral prefrontal cortex was predictive of LTM for words studied on both
      reorder and rehearse trials. These results support the view that the DLPFC
      contributes to LTM formation through its role in organization of information in
      WM.

PMID- 16421310
TI  - The role of CA3 hippocampal NMDA receptors in paired associate learning.
AB  - The hippocampus is necessary for declarative memory in humans and episodic memory
      in rodents. Considerable current research is focused on the role of plasticity
      within specific subfields of the hippocampus. Here, using a viral vector to
      temporally control a focal deletion of the NR1 gene, we show that learning novel
      paired associations between specific cues and their context is dependent on CA3
      NMDA receptors. Deletion of CA3 NR1 genes in <30% of the dorsal hippocampus was
      sufficient to disrupt new learning, whereas the same treatment does not prevent
      expression of previously acquired paired associates and does not affect the
      ability to discriminate contexts or paired associate learning when either the
      cues or the context is familiar. The findings suggest that CA3 NMDA receptors
      specifically support the encoding of new experiences to involve incidental and
      contingent associations.

PMID- 16421312
TI  - Fluent conceptual processing and explicit memory for faces are
      electrophysiologically distinct.
AB  - Implicit memory and explicit memory are fundamentally different manifestations of
      memory storage in the brain. Yet, conceptual fluency driven by previous
      experience could theoretically be responsible for both conceptual implicit memory
      and aspects of explicit memory. For example, contemplating the meaning of a word
      might serve to speed subsequent processing of that word and also make it seem
      familiar. We examined electrophysiological correlates of conceptual priming with
      180 celebrity faces to determine whether or not they resemble
      electrophysiological correlates of explicit memory. Celebrity faces are ideal for
      this purpose because they carry with them preexisting conceptual information
      (i.e., biographical facts) that can selectively be brought to mind such that
      conceptual processing can be manipulated systematically. In our experiment,
      exposure to biographical information associated with only one-half of the
      celebrities yielded conceptual priming for those faces, whereas all faces were
      perceptually primed. Conceptual priming was indexed by positive brain potentials
      over frontal regions from approximately 250 to 500 ms. Explicit memory retrieval
      was associated with later brain potentials over posterior regions that were
      strikingly similar to potentials previously associated with pure familiarity for
      faces (when a face seems familiar in the absence of retrieval of any specific
      information about previous occurrence). Furthermore, the magnitude of conceptual
      priming was correlated across subjects with the amplitude of frontal but not
      posterior potentials, whereas the opposite was true for explicit memory. Distinct
      brain processes were thus associated with conceptual priming and conscious
      recognition of faces, thus providing a sharper focus on the border between
      implicit and explicit memory.

PMID- 16421313
TI  - In vivo imaging of preferential motor axon outgrowth to and synaptogenesis at
      prepatterned acetylcholine receptor clusters in embryonic zebrafish skeletal
      muscle.
AB  - Little is known about the spatial and temporal dynamics of presynaptic and
      postsynaptic specializations that culminate in synaptogenesis. Here, we imaged
      presynaptic vesicle clusters in motor axons and postsynaptic acetylcholine
      receptor (AChR) clusters in embryonic zebrafish to study the earliest events in
      synaptogenesis in vivo. Prepatterned AChR clusters are present on muscle fibers
      in advance of motor axon outgrowth from the spinal cord. Motor axon growth cones
      and filopodia are selectively extended toward and contact prepatterned AChR
      clusters, followed by the rapid clustering of presynaptic vesicles and insertion
      of additional AChRs, hallmarks of synaptogenesis. All initially formed
      neuromuscular synapses contain AChRs that were inserted into the membrane at the
      time the prepattern is present. Examination of embryos in which AChRs were
      blocked or clustering is absent showed that neither receptor activity or receptor
      protein is required for these events to occur. Thus, during initial
      synaptogenesis, postsynaptic differentiation precedes presynaptic
      differentiation, and prepatterned neurotransmitter clusters mark sites destined
      for synapse formation.

PMID- 16421314
TI  - Localization of tactile stimuli depends on conscious detection.
AB  - Neurological reports of "tactile blindsight" suggest that the human somatosensory
      system can extract behaviorally useful information about the location of a
      tactile stimulus in the absence of conscious awareness that the stimulus occurred
      (Paillard et al., 1983; Rossetti et al., 1995). However, in a series of
      psychophysical experiments with neurologically intact subjects, we found no
      evidence for such a dissociation. Our subjects' ability to name the finger on
      which a tactile stimulus had been presented was dependent on their ability to
      consciously detect that stimulus (Harris et al., 2004). The present experiments
      followed up on this study and specifically sought evidence for a dissociation
      when subjects were required to indicate the location of the stimulus either by
      pointing at or moving the stimulated finger, the same response made by the
      neurological patients. Once again, localization accuracy was correlated with
      detection, and, crucially, when both detection and localization were measured
      using equivalent forced-choice tasks, the subjects were completely unable to
      identify the location of stimuli that they had not detected. These findings are
      inconsistent with the dissociation implied by the cases of tactile blindsight,
      but are consistent with other neurological evidence that detection of a tactile
      stimulus does not depend on localization (Head and Holmes, 1911; Halligan et al.,
      1995; Rapp et al., 2002).

PMID- 16421316
TI  - Organization of the presynaptic active zone by ERC2/CAST1-dependent clustering of
      the tandem PDZ protein syntenin-1.
AB  - Presynaptic active zones contain a cytoskeletal matrix called the CAZ, which is
      thought to play a critical role in the regulation of active zone formation and
      neurotransmitter release. Recent studies have identified several CAZ components,
      but little is known about how they contribute to the molecular organization of
      active zones. Here, we report a novel PDZ [postsynaptic density-95/Discs
      large/zona occludens-1] interaction between the CAZ protein ERC2/CAST1 and the
      tandem PDZ protein syntenin-1, which is known to associate with diverse synaptic
      proteins, including glutamate receptor subunits, SynCAM, and beta-neurexin. This
      interaction promotes the localization of syntenin-1 at presynaptic ERC2 clusters.
      In addition to the PDZ interaction, multimerization of both ERC2 and syntenin-1
      mediates syntenin-1 clustering. These results suggest that ERC2 promotes
      presynaptic syntenin-1 clustering by two distinct mechanisms and that syntenin-1
      may contribute to the molecular organization of active zones by linking ERC2 and
      other CAZ components to diverse syntenin-1-associated synaptic proteins.

PMID- 16421315
TI  - Morphine and pain-related stimuli enhance cell surface availability of somatic
      delta-opioid receptors in rat dorsal root ganglia.
AB  - The present study demonstrates that perikaryaldelta-opioid receptors (deltaORs)
      in rat dorsal root ganglion (DRG) neurons bind and internalize opioid ligands
      circulating in the CSF. Using confocal and electron microscopy, we found that
      prolonged morphine treatment increased the cell surface density of these
      perikaryal deltaORs and, by way of consequence, receptor-mediated internalization
      of the fluorescent deltorphin (DLT) analog omega-Bodipy 576/589 deltorphin-I 5
      aminopentylamide (Fluo-DLT) in all three types of DRG neurons (small, medium, and
      large). In contrast, chronic inflammatory pain induced by the injection of
      complete Freund's adjuvant (CFA) into one hindpaw selectively increased Fluo-DLT
      internalization in small and medium-sized DRG neurons ipsilateral to the
      inflammation. Based on our previous studies in the spinal cord of mu-opioid
      receptor (muOR) knock-out mice, it may be assumed that the enhanced membrane
      recruitment of deltaORs observed after sustained morphine is attributable to
      stimulation of muORs. However, the selectivity of the effect induced by
      inflammatory pain suggests that it involves a different mechanism, namely a
      modality-specific and pain-related activation of C and Adelta fibers. Indeed,
      stimulation by capsaicin of transient receptor potential vanilloid 1 receptors,
      which are selectively expressed by small diameter (< 600 microm2) DRG neurons,
      increased Fluo-DLT internalization exclusively in this cell population. The
      present results, therefore, demonstrate that DRG neurons express perikaryal
      deltaORs accessible to CSF-circulating ligands and that the density and, hence,
      presumably also the responsiveness, of these receptors may be modulated by both
      pain-related stimuli and sustained exposure to muOR agonists.

PMID- 16421317
TI  - A signaling mechanism from G alpha q-protein-coupled metabotropic glutamate
      receptors to gene expression: role of the c-Jun N-terminal kinase pathway.
AB  - Galphaq-protein-coupled group I metabotropic glutamate receptors (mGluRs) are
      densely expressed in brain neurons and are actively involved in various cellular
      activities. In this study, we investigated the role of group I mGluRs in
      regulating the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase in
      cultured neurons. We found that selective activation of mGluR5 induced a rapid
      and transient phosphorylation of JNK. In a series of studies to determine the
      mechanisms, we found that the conventional mGluR5-associated signaling pathways
      (inositol-1,4,5-triphosphate-mediated Ca2+ release and activation of protein
      kinase C) were not involved in the mGluR5 regulation. Instead, ligand stimulation
      of mGluR5 caused a dynamic transactivation of the epidermal growth factor (EGF)
      receptor, which in turn triggered a downstream signaling pathway to upregulate
      JNK phosphorylation. Furthermore, the mGluR5-dependent JNK activation
      specifically activated c-Jun, but not activating transcription factor-2 or JunD,
      and increased activator protein-1 (AP-1)-mediated endogenous transcriptional
      activity. Together, we identified a novel mGluR5-to-nucleus communication through
      the EGF/JNK pathway, which functions to regulate AP-1-mediated transcription.

PMID- 16421318
TI  - Human immunodeficiency virus (HIV)-induced neurotoxicity: roles for the NMDA
      receptor subtypes.
AB  - Neuronal damage in human immunodeficiency virus type 1 (HIV-1) infection in the
      brain is thought to occur at least in part through NMDA receptor (NMDAR)
      excitation initiated by soluble neurotoxins from HIV-infected brain macrophages.
      Furthermore, brain regions enriched in NMDAR-2A (NR2A) and NMDAR-2B (NR2B)
      subunits, such as the hippocampus, are particularly vulnerable. Using cultured
      rat hippocampal cells and HIV-1-infected human monocyte-derived macrophages
      (HIV/MDM), we examined the role of NR2A and NR2B in HIV/MDM-induced hippocampal
      neuronal death. We used the primary HIV-1 strain Jago derived from the CSF of an
      individual with HIV-associated dementia and that robustly replicates in MDM. We
      found the following: (1) hippocampal neuronal susceptibility to HIV/MDM
      excitotoxins varies according to the developmental expression patterns of NR2A
      and NR2B; (2) NMDAR activation by HIV/MDM results in neuronal calpain activation,
      which results in neuronal death; and (3) selective antagonists of homomeric
      NR2B/NR2B- and heteromeric NR2A/NR2B-containing NMDARs, as well as an inhibitor
      of calpain activity, afford neuroprotection against HIV/MDM. These studies
      establish a clear link between macrophage HIV infection, neuronal NR2A and NR2B
      activation, and calpain-mediated hippocampal neuronal death. They further suggest
      a dominant role for NR2A and NR2B in determining neuronal susceptibility in HIV
      infected brain. Antagonists of NR2A and NR2B subunits as well as inhibitors of
      calpain activation offer attractive neuroprotective approaches against HIV in
      both developing and mature brain.

PMID- 16421319
TI  - Temporal structure in zebra finch song: implications for motor coding.
AB  - Adult zebra finch songs consist of stereotyped sequences of syllables. Although
      some behavioral and physiological data suggest that songs are structured
      hierarchically, there is also evidence that they are driven by nonhierarchical,
      clock-like bursting in the premotor nucleus HVC (used as a proper name). In this
      study, we developed a semiautomated template-matching algorithm to identify
      repeated sequences of syllables and a modified dynamic time-warping algorithm to
      make fine-grained measurements of the temporal structure of song. We find that
      changes in song length are expressed across the song as a whole rather than
      resulting from an accumulation of independent variance during singing. Song
      length changes systematically over the course of a day and is related to the
      general level of bird activity as well as the presence of a female. The data also
      show patterns of variability that suggest distinct mechanisms underlying syllable
      and gap lengths: as tempo varies, syllables stretch and compress proportionally
      less than gaps, whereas syllable-syllable and gap-gap correlations are
      significantly stronger than syllable-gap correlations. There is also increased
      temporal variability at motif boundaries and especially strong positive
      correlations between the same syllables sung in different motifs. Finally, we
      find evidence that syllable onsets may have a special role in aligning syllables
      with global song structure. Generally, the timing data support a hierarchical
      view in which song is composed of smaller syllable-based units and provide a rich
      set of constraints for interpreting the results of physiological recordings.

PMID- 16421321
TI  - The role of striatum in initiation and execution of learned action sequences in
      rats.
AB  - To understand the role of striatum in motor sequence learning, we trained rats to
      perform a series of tasks measuring speed and accuracy of responding to luminance
      cues presented as discriminative stimuli for single nose pokes or for sequences
      of nose pokes in a serial reaction time task. Habit (stimulus-response) learning
      was measured by comparing performances when stimuli were repeated (predictable)
      with when they were selected randomly (unpredictable). Sequences had defined
      start and end points and were limited to five nose pokes to minimize chunking.
      When sequences were repeated, response time (RT) increased for nose pokes
      initiating the sequence and decreased for nose pokes completing it. These effects
      developed incrementally across sessions, consistent with the time course of habit
      learning. Medial (mCPu), lateral, and complete (CPu) caudate-putamen lesions
      affected speed and accuracy of single nose poke responses, confirming the role of
      these areas in guiding responses with external sensory stimuli. None of these
      lesions affected the short-term increase in accuracy observed when single nose
      poke responses were repeated. Both mCPu and CPu lesions increased RTs for
      initiating sequential responses, effects that were exacerbated across sessions in
      which specific sequences were repeated. None of the lesions affected the gradual
      decrease in RT for nose pokes completing repeated sequences. Correlational
      analyses confirmed the relationship between the extent of dorsal striatal damage
      and the ability to respond to brief luminance cues and to initiate learned
      sequences. These results provide evidence implicating dorsal striatum in higher
      level organizational aspects of learning reflected in planning that precedes the
      execution of learned action sequences.

PMID- 16421320
TI  - Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal
      inhibition through LIM kinase and Slingshot phosphatase.
AB  - Myelin-associated inhibitors (MAIs) signal through a tripartate receptor complex
      on neurons to limit axon regeneration in the CNS. Inhibitory influences
      ultimately converge on the cytoskeleton to mediate growth cone collapse and
      neurite outgrowth inhibition. Rho GTPase and its downstream effector Rho kinase
      are key signaling intermediates in response to MAIs; however, the links between
      Rho and the actin cytoskeleton have not been fully defined. We found that Nogo
      66, a potent inhibitory fragment of Nogo-A, signals through LIM (LIM is an
      acronym of the three gene products Lin-11, Isl-1, and Mec-3) kinase and Slingshot
      (SSH) phosphatase to regulate the phosphorylation profile of the actin
      depolymerization factor cofilin. Blockade of LIMK1 activation and subsequent
      cofilin phosphorylation circumvents myelin-dependent inhibition in chick dorsal
      root ganglion neurons, suggesting that phosphorylation and inactivation of
      cofilin is critical for neuronal inhibitory responses. Subsequent activation of
      SSH1 phosphatase mediates cofilin dephosphorylation and reactivation.
      Overexpression of SSH1 does not mimic the neurite outgrowth inhibitory effects of
      myelin, suggesting an alternative role in MAI inhibition. We speculate that SSH
      mediated persistent cofilin activation may be responsible for maintaining an
      inhibited neuronal phenotype in response to myelin inhibitors.

PMID- 16421322
TI  - Two signaling pathways regulate the expression and secretion of a neuropeptide
      required for long-term facilitation in Aplysia.
AB  - Activation of several signaling pathways contributes to long-term synaptic
      plasticity, but how brief stimuli produce coordinated activation of these
      pathways is not understood. In Aplysia, the long-term facilitation (LTF) of
      sensory neuron synapses by 5-hydroxytryptamine (serotonin; 5-HT) requires the
      activation of several kinases, including mitogen-activated protein kinase (MAPK).
      The 5-HT-enhanced secretion of the sensory neuron-specific neuropeptide sensorin
      mediates the activation of MAPK. We find that stimulus-induced activation of two
      signaling pathways, phosphoinositide 3-kinase (PI3K) and type II protein kinase A
      (PKA), regulate sensorin secretion and responses. Treatment with 5-HT produces a
      rapid increase in sensorin synthesis, especially at varicosities, which precedes
      the secretion of sensorin. PI3K inhibitor and rapamycin block LTF and the rapid
      synthesis of sensorin at varicosities even in the absence of sensory neuron cell
      bodies. Secretion of the newly synthesized sensorin from the varicosities and
      activation of the autocrine responses of sensorin to produce LTF require type II
      PKA interaction with AKAPs (A-kinase anchoring proteins). Thus, long-term
      synaptic plasticity is produced when multiple signaling pathways that are
      important for regulating distinct cellular functions are activated in a specific
      sequence and recruit the secretion of a neuropeptide to activate additional
      critical pathways.

PMID- 16421323
TI  - Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin splice
      variants.
AB  - Arrestins constitute a family of small cytoplasmic proteins that mediate
      deactivation of G-protein-coupled receptors (GPCRs) and are known to be essential
      for cascade inactivation and receptor desensitization. Alternative splicing
      produces an array of arrestin gene products that have widely different
      specificities for their cognate receptors in vitro, but the differential
      functions of these splice variants in vivo are essentially unknown. Bovine rod
      photoreceptors express two splice variants of visual arrestin (p44 and p48) that
      display different affinities for the GPCR rhodopsin. To determine the functions
      of these splice variants in intact cells, we expressed a transgene encoding
      either a truncated form of murine arrestin (mArr(1-369), or m44) or the long
      (p48) isoform in mouse rods lacking endogenous arrestin (Arr-/-). Morphological
      analysis showed that expression of either variant attenuated the light-induced
      degeneration that is thought to result from excessive cascade activity in Arr-/
      rods. Suction electrode recordings from individual rods indicated that the
      expression of either m44 or p48 splice variants could restore normal kinetics to
      Arr-/- dim flash responses, indicating that both isoforms can bind to and quench
      phosphorylated rhodopsin rapidly. To our surprise, only the full-length variant
      was able to alter the kinetics of responses in rods lacking both arrestin and
      rhodopsin kinase, indicating that p48 can also quench the activity of
      nonphosphorylated rhodopsin.

PMID- 16421325
TI  - Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a
      model of fetal alcohol exposure.
AB  - Although some studies showed the efficacy of phosphodiesterase (PDE) inhibitors
      as neuronal plasticity enhancers, little is known about the effectiveness of
      these drugs to improve plasticity in cases of mental retardation. Fetal alcohol
      syndrome (FAS) is the leading cause of mental retardation in the western world.
      Using a combination of electrophysiological and optical imaging techniques, we
      show here that vinpocetine, a PDE type I inhibitor, restores ocular dominance
      plasticity in the ferret model of fetal alcohol exposure. Our finding should
      contribute to a better understanding and treatment of cognitive deficits
      associated with mental disorders, such as FAS.

PMID- 16421326
TI  - Automatic and intrinsic auditory "what" and "where" processing in humans revealed
      by electrical neuroimaging.
AB  - The auditory system includes 2 parallel functional pathways-one for treating
      sounds' identities and another for their spatial attributes (so-called "what" and
      "where" pathways). We examined the spatiotemporal mechanisms along auditory
      "what" and "where" pathways and whether they are automatically engaged in
      differentially processing spatial and pitch information of identical stimuli.
      Electrical neuroimaging of auditory evoked potentials (i.e., statistical analyses
      of waveforms, field strength, topographies, and source estimations) was applied
      to a passive "oddball" paradigm comprising 2 varieties of blocks of trials. On
      "what" blocks, band-pass-filtered noises varied in pitch, independently of
      perceived location. On "where" blocks, the identical stimuli varied in perceived
      location independently of pitch. Beginning 100 ms poststimulus, the electric
      field topography significantly differed between conditions, indicative of the
      automatic recruitment of distinct intracranial generators. A distributed linear
      inverse solution and statistical analysis thereof revealed activations within
      superior temporal cortex and prefrontal cortex bilaterally that were common for
      both conditions, as well as regions within the right temporoparietal cortices
      that were selective for the "where" condition. These findings support models of
      automatic and intrinsic parallel processing of auditory information, such that
      segregated processing of spatial and pitch features may be an organizing
      principle of auditory function.

PMID- 16421324
TI  - Molecular and morphological heterogeneity of neural precursors in the mouse
      neocortical proliferative zones.
AB  - The proliferative ventricular zone (VZ) is the main source of projection neurons
      for the overlying cerebral neocortex. The number and diversity of neocortical
      neurons is determined, in part, by factors controlling the proliferation and
      specification of VZ cells during embryonic development. We used a variety of
      methods, including in utero electroporation with specific cellular markers,
      computer-assisted serial EM cell reconstruction, and time-lapse multiphoton
      imaging to characterize the molecular and morphological characteristics of the VZ
      constituents and to capture their behavior during cell division. Our analyses
      reveal at least two types of dividing cells in the VZ: (1) radial glial cells
      (RGCs) that span the entire neocortical wall and maintain contact both at the
      ventricular and pial surfaces throughout mitotic division, and (2) short neural
      precursors (SNPs) that possess a ventricular endfoot and a basal process of
      variable length that is retracted during mitotic division. These two precursor
      cell classes are present concomitantly in the VZ, but their relative number
      changes over the course of cortical neurogenesis. Moreover, the SNPs are
      morphologically, ultrastructurally and molecularly distinct from dividing RGCs.
      For example, SNPs are marked by their preferential expression of the tubulin
      alpha-1 promoter whereas RGCs instead express the glutamate-aspartate transporter
      and brain lipid binding protein promoters. In contrast to recent studies that
      suggest that RGCs are the sole type of VZ precursor, the present study indicates
      that the VZ in murine dorsal telencephalon is similar to that in human and
      nonhuman primates, because it contains multiple types of neuronal precursors.

PMID- 16421327
TI  - Neuroanatomical correlates of extraversion and neuroticism.
AB  - Introversion/extraversion and neuroticism are 2 important and frequently studied
      dimensions of human personality. These dimensions describe individual differences
      in emotional responding across a range of situations and may contribute to a
      predisposition for psychiatric disorders. Recent neuroimaging research has begun
      to provide evidence that neuroticism and introversion/extraversion have specific
      functional and structural neural correlates. Previous studies in healthy adults
      have reported an association between neuroticism, introversion/extraversion, and
      the activity of the prefrontal cortex and amygdala. Studies of individuals with
      psychopathological states have also indicated that anatomic variations in these
      brain areas may relate to extraversion and neuroticism. The purpose of the
      present study was to examine selected structural correlates of neuroticism and
      extraversion in healthy subjects (n = 28) using neuroanatomic measures of the
      cerebral cortex and amygdala. We observed that the thickness of specific
      prefrontal cortex regions correlates with measures of extraversion and
      neuroticism. In contrast, no such correlations were observed for the volume of
      the amygdala. The results suggest that specific aspects of regional prefrontal
      anatomy are associated with specific personality traits.

PMID- 16421328
TI  - Time representations can be made from nontemporal information in the brain: an
      MEG study.
AB  - Perceiving the passage of time is an essential ability for humans and animals.
      Here we used magnetoencephalography and investigated how our internal clock
      system in the brain converts sensory experiences into their time representations.
      We focused on neural activities in the high-level visual areas of human subjects
      when they saw visual patterns and estimated the duration of their presentation.
      The activities in the visual areas could give us neural indices about when
      subjects perceived the appearance and disappearance of visual patterns, thus
      enabling us to measure the stimulus duration "in the brain." Comparing these
      neural indices of time with subjective durations of stimuli measured
      psychophysically, we showed that, under some circumstances, these 2 durations can
      be dissociated in the opposite directions: although the neural index signals a
      "longer" interval of a stimulus over another one, it is perceived as "shorter" in
      subjective time scale. Instead, we found that these subjective intervals are
      closely linked to the strength, not timings, of neural activity evoked by visual
      patterns. Our results indicate that "nontemporal information" of perceptual
      neural activity, such as the strength (not latency) of neural responses, can
      influence the shaping of time representations in our brain.

PMID- 16421329
TI  - The role of semantics and grammatical class in the neural representation of
      words.
AB  - On the basis of neuropsychological and functional imaging evidence, meaning and
      grammatical class (particularly the verb-noun distinction) have been proposed as
      organizational principles of linguistic knowledge in the brain. However, previous
      studies investigating verb and noun processing have been confounded by the
      presence of systematic correlations between word meaning and grammatical class.
      In this positron emission tomography study, we investigated implicit word
      processing using stimuli that allowed the effects of semantic and grammatical
      properties to be examined independently, without grammatical-semantic confounds.
      We found that left hemisphere cortical activation during single-word processing
      was modulated by word meaning, but not by grammatical class. Motor word
      processing produced significant activation in left precentral gyrus, whereas
      sensory word processing produced significant activation in left inferior temporal
      and inferior frontal regions. In contrast to previous studies, there were no
      effects of grammatical class in left inferior frontal gyrus (IFG). Instead, we
      found semantic-based differences within left IFG: anterior, but not posterior,
      left IFG regions responded preferentially to sensory words. These findings
      demonstrate that the neural substrates of implicit word processing are determined
      by semantic rather than grammatical properties and suggest that word
      comprehension involves the activation of modality-specific representations linked
      to word meaning.

PMID- 16421330
TI  - Ventromedial prefrontal cortex is obligatory for consolidation and
      reconsolidation of object recognition memory.
AB  - Once consolidated, a long-term memory item could regain susceptibility to
      consolidation blockers, that is, reconsolidate, upon its reactivation. Both
      consolidation and reconsolidation require protein synthesis, but it is not yet
      known how similar these processes are in terms of molecular, cellular, and neural
      circuit mechanisms. Whereas most previous studies focused on aversive
      conditioning in the amygdala and the hippocampus, here we examine the role of the
      ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of
      object recognition memory. Object recognition memory is the ability to
      discriminate the familiarity of previously encountered objects. We found that
      microinfusion of the protein synthesis inhibitor anisomycin or the N-methyl-D
      aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV)
      into the vmPFC, immediately after training, resulted in impairment of long-term
      (24 h) but not short-term (3 h) recognition memory. Similarly, microinfusion of
      anisomycin or APV into the vmPFC immediately after reactivation of the long-term
      memory impaired recognition memory 24 h, but not 3 h, post-reactivation. These
      results indicate that both protein synthesis and NMDA receptors are required for
      consolidation and reconsolidation of recognition memory in the vmPFC.

PMID- 16421331
TI  - Differential functions of lateral and medial rostral prefrontal cortex (area 10)
      revealed by brain-behavior associations.
AB  - We analyzed the behavioral data from 104 neuroimaging studies using positron
      emission tomography or functional magnetic resonance imaging that reported
      activation peaks in rostral prefrontal cortex (PFC), approximating Brodmann's
      area 10. The distribution of absolute x coordinates of activation peaks (i.e., x
      coordinate regardless of hemisphere) differed significantly from a unimodal
      normal distribution, reflecting distinct clusters of activation in lateral and
      medial subregions. These 2 clusters were associated with different patterns of
      behavioral data. Lateral activations were associated with contrasts between
      experimental and control conditions where response times (RTs) were slower in the
      experimental condition. Medial activations were associated with contrasts where
      RTs were, if anything, faster in experimental than control conditions. These
      findings place important constraints on theories of rostral PFC functions.

PMID- 16421332
TI  - Effects of healthy aging on hippocampal and rhinal memory functions: an event
      related fMRI study.
AB  - Event-related functional magnetic resonance imaging was used to study the effects
      of healthy aging on hippocampal and rhinal memory functions. Memory for past
      events can be based on retrieval accompanied by specific contextual details
      (recollection) or on the feeling that an event is old or new without the recovery
      of contextual details (familiarity). There is evidence that recollection is more
      dependent on hippocampus, whereas familiarity is more dependent on the rhinal
      cortex, and that healthy aging has greater effects on recollection than on
      familiarity. However, little evidence is available about the neural correlates of
      these effects. Here, we isolated activity associated with recollection and
      familiarity by distinguishing between linear and quasi-exponential "perceived
      oldness" functions derived from recognition confidence levels. The main finding
      was a double dissociation within the medial temporal lobes between recollection
      related activity in hippocampus, which was reduced by aging, and familiarity
      related activity in rhinal cortex, which was increased by aging. In addition, age
      dissociations were found within parietal and posterior midline regions. Finally,
      aging reduced functional connectivity within a hippocampal
      retrosplenial/parietotemporal network but increased connectivity within a rhinal
      frontal network. These findings indicate that older adults compensate for
      hippocampal deficits by relying more on rhinal cortex, possibly through a top
      down frontal modulation. This finding has important clinical implications because
      early Alzheimer's disease impairs both hippocampus and rhinal cortex.

PMID- 16421333
TI  - A locus on chromosome 9p confers susceptibility to ALS and frontotemporal
      dementia.
AB  - OBJECTIVE: To perform genetic linkage analysis in a family affected with ALS and
      frontotemporal dementia (FTD). METHODS: The authors performed a genome-wide
      linkage analysis of a four-generation, 50-member Scandinavian family in which
      five individuals were diagnosed with ALS and nine with FTD. Linkage calculations
      assuming autosomal dominant inheritance of a single neurodegenerative disease
      manifesting as either ALS or FTD with age-dependent penetrance were performed.
      Further analyses for ALS alone and FTD alone were performed. A parametric
      logarithm of odds (lod) score of 2.0 or greater was required for further study of
      a potential locus and crossover (haplotype) analysis. RESULTS: A new ALS-FTD
      locus was identified between markers D9s1870 and D9s1791 on human chromosome
      9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers
      D9s1121 and D9s2154. Crossover analysis indicates this region covers
      approximately 21.8 cM, or 14Mb. CONCLUSIONS: A locus on chromosome 9p21.3-p13.3
      is linked to ALS-FTD.

PMID- 16421334
TI  - Achieving healthy weight in African-American communities: research perspectives
      and priorities.
AB  - The longstanding high burden of obesity in African-American women and the more
      recent, steeper than average rise in obesity prevalence among African-American
      children constitute a mandate for an increased focus on obesity prevention and
      treatment research in African-American communities. The African-American
      Collaborative Obesity Research Network (AACORN) was formed to stimulate and
      support greater participation in framing and implementing the obesity research
      agenda by investigators who have both social and cultural grounding in African
      American life experiences and obesity-related scientific expertise. AACORN's
      examination of obesity research agenda issues began in 2003 in conjunction with
      the Think Tank on Enhancing Obesity Research at the National Heart, Lung, and
      Blood Institute (NHLBI). The assessment was subsequently expanded to take into
      account the overall NIH strategic plan for obesity research, literature reviews,
      and descriptions of ongoing studies. In identifying priorities, AACORN members
      considered the quality, quantity, focus, and contextual relevance of published
      research relevant to obesity prevention and treatment in African-American adults
      or children. Fifteen recommended research priorities are presented in five
      categories adapted from the NHLBI Think Tank proceedings: health effects, social
      and environmental context, prevention and treatment, research methods, and
      research training and funding. These recommendations from an African-American
      perspective build on and reinforce certain aspects of the NHLBI and overall NIH
      research agendas by providing more specific rationale and directions on areas for
      enhancement in the type of research being done or in the conceptualization and
      implementation of that research.

PMID- 16421335
TI  - Prediction of visceral adipose tissue using air displacement plethysmography in
      children.
AB  - OBJECTIVE: To determine the ability of air displacement plethysmography (ADP) to
      predict visceral adipose tissue (VAT) volume in children. RESEARCH METHODS AND
      PROCEDURES: Fifty-five (33 boys/22 girls) white children 13 to 14 years old were
      studied. Anthropometric measures were collected for body mass, stature, BMI, and
      waist-to-hip ratio (WHR), and body fat percentage was estimated from triceps and
      subscapular skinfolds, bioelectrical impedance analysis, and ADP. VAT volume was
      determined using magnetic resonance imaging, using a multiple slice protocol at
      levels L1 to L5. RESULTS: Boys had significantly (p < or = 0.05) less VAT volume
      than girls [645.1 (360.5) cm(3) vs. 1035.8 (717.3) cm(3)]. ADP explained the
      greatest proportion of the variance in VAT volume compared with the other
      anthropometric measures. Multiple regression analysis indicated that VAT volume
      was best predicted by ADP body fat percentage in boys [r(2) = 0.81, SE of the
      estimate (SEE) = 160.1, SEE coefficient of variation = 25%] and by WHR and BMI in
      girls (r(2) = 0.80, SEE = 337.71, SEE coefficient of variation = 33%).
      DISCUSSION: Compared with the other anthropometric measures, ADP explains the
      greatest proportion of the variance in VAT volume in children 13 to 14 years old.
      For boys, ADP is the tool of choice to predict VAT volume, yet using the more
      simply collected measures of BMI and WHR is recommended for girls. However, large
      SE of the estimates remained, suggesting that if precision is needed, there is no
      surrogate for direct imaging of VAT.

PMID- 16421336
TI  - Characteristics of patients undergoing bariatric surgery in Canada.
AB  - OBJECTIVE: The increasing prevalence of obesity has led to an increased use of
      bariatric surgery in the treatment of severely obese individuals. The
      characteristics of patients undergoing bariatric procedures outside of clinical
      studies and on a national level have not previously been reported. RESEARCH
      METHODS AND PROCEDURES: Acute-care hospital discharge data from the Canadian
      Institute for Health Information were analyzed to determine the demographic and
      clinical features and in-hospital mortality rates of individuals undergoing
      bariatric surgery in Canada. Data from individuals undergoing surgery in fiscal
      year 2002/2003 were compared with data from 1993/1994. RESULTS: Over 1100
      bariatric surgeries were performed in Canada in 2002/2003, with the vast majority
      being performed in middle-aged women. Ten percent of patients had hypertension or
      diabetes, and only 1% or fewer had dyslipidemia or cardiovascular or
      cerebrovascular disease. Compared with 1993/1994, patients undergoing surgery in
      2002/2003 were older, more likely to have diabetes or hypertension, and had
      shorter hospital stays. In-hospital mortality rates were <1% in both years.
      DISCUSSION: In the last decade, there has been a small increase in the average
      age and the number of patients with concomitant cardiovascular risk factors who
      are undergoing bariatric procedures in Canada. However, the vast majority of
      surgeries are being performed in middle-aged women with little cardiovascular
      comorbidity, and this is likely contributing to very low in-hospital death rates.
      Such individuals likely represent a highly selected sample of severely obese
      patients within Canada.

PMID- 16421337
TI  - Peptide-YY levels after a fat load in black and white women.
AB  - OBJECTIVE: To determine whether basal plasma peptide-YY (PYY) levels in
      overweight, middle-aged black women are different from those of white women of
      similar BMI and age and ascertain whether there is a difference between the two
      groups in plasma PYY levels in response to a liquid high fat load. RESEARCH
      METHODS AND PROCEDURES: Using a commercial radioimmunoassay kit, the
      concentration of PYY was measured at baseline and at 2, 4, 6, and 8 hours after
      ingesting a fatty liquid meal (86.5% of the calories from fat) in 12 black and 12
      white women who were matched for age and BMI. RESULTS: PYY levels (picograms per
      milliliter) at baseline and at every other time-point of the test meal were
      significantly lower in the black than in the white group. In addition, the change
      in PYY concentration from baseline was lower in the black than in the white group
      only at 8 hours after the meal. DISCUSSION: The lower baseline level and the
      blunted PYY response of the black women to the fat load indicated that this
      signal for appetite suppression was reduced, which, in turn, might contribute to
      the enhanced obesity of the black women.

PMID- 16421338
TI  - Glucose-dependent insulin modulation of oscillatory lipolysis in perifused rat
      adipocytes.
AB  - OBJECTIVE: We showed glucose-dependent lipolytic oscillations in adipocytes that
      are modulated by free fatty acids (FFAs). We hypothesized that the oscillations
      are driven by oscillatory glucose metabolism that leads to oscillatory formation
      of alpha-glycerophosphate (alpha-GP), oscillatory removal of long-chain coenzyme
      A (LC-CoA) by alpha-GP to form triglycerides, and oscillatory relief of LC-CoA
      inhibition of triglyceride lipases. This study examined the effect of insulin on
      this hypothesis. RESEARCH METHODS AND PROCEDURES: Samples were collected every
      minute from perifused rat adipocytes during the basal state followed by insulin
      (+/-glucose) or isoproterenol (+/-insulin; n = 4 each). RESULTS: Insulin caused a
      significant increase in glycerol release (18%), with a concomitant significant
      decrease in FFA release (38%). Without glucose, insulin had no effect on glycerol
      release while still decreasing FFA release (35%). Insulin (5 microU/mL)
      attenuated the response of lipolysis to isoproterenol (approximately 3-fold
      increase with isoproterenol vs. 2-fold increase with insulin + isoproterenol).
      However, 1 mU/mL insulin amplified the lipolytic response ( approximately 5-fold
      increase in glycerol release with insulin + isoproterenol), with a concomitant
      increase in FFA reesterification (no increase in FFA release compared with
      isoproterenol alone). DISCUSSION: We interpret these results to be due to
      insulin's ability to increase glucose uptake and conversion to alpha-GP, thus
      removing LC-CoA inhibition of triglyceride lipases. While the physiological
      importance of lipolytic oscillations remains to be determined, we hypothesize
      that such an oscillation may play an important role in the delivery of FFAs to
      the liver, beta cells, and other tissues.

PMID- 16421339
TI  - Thyroid-stimulating hormone stimulates interleukin-6 release from 3T3-L1
      adipocytes through a cAMP-protein kinase A pathway.
AB  - OBJECTIVE: Thyroid-stimulating hormone (TSH) is a novel modulator of adipokine
      release from human and mouse adipocytes. The aim of our study was to identify the
      signal transduction pathways activated by TSH that stimulate interleukin (IL)-6
      production. RESEARCH METHODS AND PROCEDURES: Mouse 3T3-L1 preadipocyte and
      differentiated adipocyte cell cultures were studied. The effect of 0 to 1 microM
      TSH on IL-6 protein release into the medium over 0 to 24 hours was assessed. TSH
      signaling pathways responsible for regulating IL-6 were studied through the use
      of 1 muM forskolin, 100 microM 8-pCPT-2'-O-Me-cAMP, 10 microM H89, 50 microM
      PD98059, and 2 mug/mL actinomycin D. RESULTS: TSH stimulated IL-6 release by 2.6
      fold from 3T3-L1 adipocytes at concentrations as low as 0.01 microM but did not
      alter IL-6 production of corresponding preadipocytes. Forskolin (elevates
      intracellular cAMP) stimulated IL-6 release from 3T3-L1 adipocytes (n = 3, p <
      0.005), and H89, an inhibitor of cAMP-dependent protein kinase A (PKA), reduced
      TSH-stimulated IL-6 release by 66% (n = 3, p < 0.01), indicating a requirement
      for cAMP-dependent PKA. Inhibition of the mitogen-activated protein kinase
      pathway with PD98059 did not affect TSH-stimulated IL-6 release. Activation of an
      alternate cAMP target, the exchange protein of cAMP, with 8-pCPT-2'-O-Me-cAMP,
      had no effect on IL-6 release. TSH raised the level of IL-6 mRNA, and blockade of
      transcription with actinomycin D abrogated IL-6 protein release by TSH (n = 3, p
      < 0.05). DISCUSSION: TSH stimulates IL-6 release from differentiated 3T3-L1
      adipocytes, but not preadipocytes, by signaling through cAMP-PKA to activate IL-6
      gene transcription.

PMID- 16421340
TI  - Evidence in female rhesus monkeys (Macaca mulatta) that nighttime caloric intake
      is not associated with weight gain.
AB  - OBJECTIVE: To evaluate the hypothesis that nighttime consumption of calories
      leads to an increased propensity to gain weight. RESEARCH METHODS AND PROCEDURES:
      Sixteen female rhesus monkeys (Macaca mulatta) were ovariectomized and placed on
      a high-fat diet to promote weight gain, and we examined whether monkeys that ate
      a high percentage of calories at night were more likely to gain weight than
      monkeys that ate the majority of calories during the day. RESULTS: Within 6 weeks
      post-ovariectomy, calorie intake and body weight increased significantly (129 +/-
      14%, p = 0.04; 103 +/- 0.91%, p = 0.02, respectively). Subsequent placement on
      high-fat diet led to further significant increases in calorie intake and body
      weight (368 +/- 56%, p = 0.001; 113 +/- 4.0%, p = 0.03, respectively). However,
      there was no correlation between the increase in calorie intake and weight gain
      (p = 0.34). Considerable individual variation existed in the percentage of
      calories consumed at night (6% to 64% total daily caloric intake). However, the
      percentage of calorie intake occurring at night was not correlated with body
      weight (r = 0.04; p = 0.87) or weight gain (r = 0.07; p = 0.79) over the course
      of the study. Additionally, monkeys that showed the greatest nighttime calorie
      intake did not gain more weight (p = 0.94) than monkeys that showed the least
      nighttime calorie intake. DISCUSSION: These results show that eating at night is
      not associated with an increased propensity to gain weight, suggesting that
      individuals trying to lose weight should not rely on decreasing evening calorie
      intake as a primary strategy for promoting weight loss.

PMID- 16421341
TI  - Muscle type-dependent responses to insulin in intramyocellular triglyceride
      turnover in obese rats.
AB  - OBJECTIVE: To understand the role of hyperinsulinemia in intramyocellular (imc)
      triglyceride (TG) accumulation and in regulating imcTG turnover. RESEARCH METHODS
      AND PROCEDURES: imcTG was first prelabeled by continuous infusion of [U
      (14)C]glycerol (pulse), and then the rate of label loss from the prelabeled imcTG
      pool (turnover) in gastrocnemius, tibialis anterior, and soleus muscle of awake,
      high-fat-fed obese rats during the subsequent hyperinsulinemic-euglycemic clamp
      experiments (chase) was determined. RESULTS: Post-absorptive basal fractional
      imcTG turnover rate in soleus was 0.010 +/- 0.001/min, significantly lower than
      that in gastrocnemius (0.026 +/- 0.002/min, p < 0.001) or tibialis anterior
      (0.030 +/- 0.002/min, p < 0.0001), a pattern reciprocal to their imcTG pool size.
      Insulin infusion at 25 pmol/kg per minute resulted in pathophysiological
      hyperinsulinemia (5-fold increase over the baseline value). This caused an
      increase in imcTG turnover by 3-fold in soleus (0.029 +/- 0.006/min, p = 0.002)
      but a decrease in gastrocnemius (0.012 +/- 0.003/min, p = 0.001) and in tibialis
      anterior (0.0064 +/- 0.001/min, p < 0.0001). Pathophysiological hyperinsulinemia
      suppressed hormone-sensitive lipase activity in heart (p = 0.01) and mesenteric
      fat (p = 0.05) but not in skeletal muscle (p > 0.05). The pool size of imcTG was
      not affected by hyperinsulinemia. DISCUSSION: The results demonstrated muscle
      type dependence in the response of imcTG turnover to hyperinsulinemia in the
      obesity model. The reciprocal insulin effects on imcTG turnover in oxidative vs.
      oxidative-glycolytic muscle indicated a possibility that oxidative muscle
      contributes more to insulin resistance under hyperinsulinemia if imcTG-fatty acid
      oxidation is a function of turnover. imcTG turnover does not seem to regulate
      imcTG pool size acutely.

PMID- 16421342
TI  - Intramyocellular lipid content and molecular adaptations in response to a 1-week
      high-fat diet.
AB  - OBJECTIVE: To investigate molecular adaptations that accompany the elevation of
      intramyocellular lipid (IMCL) content on a high-fat (HF) diet for 1 week.
      RESEARCH METHODS AND PROCEDURES: Ten subjects consumed a normal-fat (NF) diet for
      1 week, followed by an HF diet for another week. After both dietary periods, we
      determined the IMCL content by proton magnetic resonance spectroscopy in the
      vastus lateralis muscle and quantified changes in gene expression, protein
      content, and activity in biopsy samples. We investigated genes involved in
      carbohydrate and fatty acid handling [lipoprotein lipase, acetyl-coenzyme A
      carboxylase (ACC) 2, hormone-sensitive lipase, hexokinase II, and glucose
      transporter 4] and measured protein levels of CD36 and phosphorylated and
      unphosphorylated ACC2 and the activity of adenosine monophosphate-activated
      kinase. RESULTS: IMCL content was increased by 54% after the HF period.
      Lipoprotein lipase mRNA concentration was increased by 33%, whereas ACC2 mRNA
      concentration tended to be increased after the HF diet. Hexokinase II, glucose
      transporter 4, and hormone-sensitive lipase mRNA were unchanged after the HF
      diet. ACC2 and CD36 protein levels, phosphorylation status of ACC2, and adenosine
      monophosphate-activated kinase activity did not change in response to the HF
      diet. DISCUSSION: We found that IMCL content in skeletal muscle increased after 1
      week of HF feeding, accompanied by molecular adaptations that favor fat storage
      in muscle rather than oxidation.

PMID- 16421343
TI  - Adolescent sex differences in adiponectin are conditional on pubertal development
      and adiposity.
AB  - OBJECTIVE: Adiponectin is an adipose tissue protein with important insulin
      sensitizing, anti-inflammatory, and cardioprotective properties but is
      paradoxically lower in obese individuals. Sex differences in adiponectin have
      been reported in adults and adolescents but not in prepubertal children. In this
      study, we hypothesized that sex differences in adiponectin would develop during
      puberty and would be influenced by level of adiposity. RESEARCH METHODS AND
      PROCEDURES: Adiponectin levels were measured in 1196 white and African-American
      adolescents. Insulin resistance was estimated using the homeostasis model (HOMA
      IR). Demographic, developmental, and metabolic variables, including interactions
      with adiposity measurements, were evaluated for independent relationships with
      adiponectin levels. RESULTS: Overall, adiponectin levels varied significantly by
      sex, race, adiposity, and puberty stage. Significant sex differences in
      adiponectin developed after the onset of puberty, particularly in lean
      adolescents. Adolescent boys had lower adiponectin levels in post-puberty
      compared with pre-puberty (p = 0.01) and had lower levels than girls in both
      puberty and post-puberty (both p < 0.001), after adjusting for race, BMI z-score,
      and natural logarithm-(HOMA-IR). Sex differences were also conditional on
      adiposity level, with significant sex differences among lean (p < 0.001) but not
      among non-lean (p = 0.16) adolescents. Adiponectin levels in girls decreased more
      with increasing adiposity than in boys (p = 0.004), but only marginally so after
      standardizing for girls' higher mean adiponectin level (p = 0.11). DISCUSSION:
      Sex differences in adiponectin are dependent on both puberty stage and adiposity
      in adolescents, such that by post-puberty, non-lean boys exhibit the lowest
      levels of adiponectin.

PMID- 16421344
TI  - Effect of low- and high-calcium dairy-based diets on macronutrient oxidation in
      humans.
AB  - OBJECTIVE: Higher calcium and dairy intakes may be associated with lower body
      weights, but a mechanism in humans has yet to be elucidated. We compared the
      effects of a dairy-based high-calcium diet and a low-calcium diet on
      macronutrient oxidation. RESEARCH METHODS AND PROCEDURES: Subjects (10 men and
      nine women) consumed a low-dairy (LD, approximately one serving per day,
      approximately 500 mg Ca(2+)/d) or high-dairy (HD, approximately three to four
      servings per day, approximately 1400 mg Ca(2+)/d) energy balance diet for 1 week.
      Each diet condition was performed twice. On the 7th day, subjects were studied in
      a room calorimeter under one of four study conditions, applied in a randomized
      crossover design. Within each diet condition, subjects were studied under
      conditions of energy balance and acute energy deficit. The deficit (-600 kcal/d)
      was induced only for the 24 hours that subjects resided in the room and was
      achieved by a combination of caloric restriction and exercise. RESULTS: Under
      energy balance conditions, there was no effect of diet treatment on respiratory
      quotient or 24-hour macronutrient oxidation. Under energy deficit conditions, 24
      hour fat oxidation was significantly increased on the HD diet (HD with deficit =
      136 +/- 13 g/d, LD with deficit = 106 +/- 7 g/d, p = 0.02). DISCUSSION:
      Consumption of a dairy-based high-calcium diet increased 24-hour fat oxidation
      under conditions of acute energy deficit. We hypothesize that these effects are
      due to an increased fat oxidation during exercise.

PMID- 16421345
TI  - ACDC/adiponectin and PPAR-gamma gene polymorphisms: implications for features of
      obesity.
AB  - OBJECTIVE: The main purpose of this study was to investigate associations of
      single-nucleotide polymorphisms (SNPs) in the adipocyte C1q and collagen domain
      containing (ACDC) gene and its regulator, the nuclear peroxisome proliferator
      activated receptor (PPAR)-gamma gene, with body fat mass and its topographical
      distribution in postmenopausal women. RESEARCH METHODS AND PROCEDURES:
      Participants were 1501 healthy women, 60 to 85 years old, who were genotyped for
      four SNPs in the ACDC gene (-11391G/A, -11377C/G, +45T/G, +276G/T) and the
      Pro12Ala SNP in the PPAR-gamma gene. Total body fat mass and the central to
      peripheral fat mass ratio (CFM/PFM ratio) were measured using DXA. Adiponectin
      and homeostasis model assessment of insulin resistance were measured in 287
      subjects. RESULTS: The -11377C/G SNP was associated with adiponectin (p < 0.001)
      and the CFM/PFM ratio (p = 0.005); the G allele being associated with low
      adiponectin and high CFM/PFM ratio. Similar associations of adiponectin (p =
      0.0001) and the CFM/PFM ratio (p = 0.002) characterized the 1_2 (G_G) promoter
      haplotype (11391G/A_-11377C/G). Genotype variation of SNP Pro12Ala was associated
      with total body fat mass (p = 0.04); women with GG being the most obese (p =
      0.01). The Ala/Ala (GG) genotype of Pro12Ala SNP interacted with the CC genotype
      of SNP-11377C/G in the determination of BMI (p = 0.001), when analyzed using a
      codominant model. DISCUSSION: Polymorphisms in the ACDC gene are associated with
      body fat distribution, whereas the Pro12Ala polymorphism in PPAR-gamma is
      associated with overall adiposity, apparently in interaction with an ACDC
      promoter SNP.

PMID- 16421346
TI  - Meta-analysis on the G-308A tumor necrosis factor alpha gene variant and
      phenotypes associated with the metabolic syndrome.
AB  - OBJECTIVE: The G-308A tumor necrosis factor (TNF) alpha gene variant has been
      associated with obesity, insulin resistance, and hypertension. We performed a
      systematical review of the literature by means of a meta-analysis to assess the
      association of the G-308A TNFalpha polymorphism with the components of the
      metabolic syndrome. RESEARCH METHODS AND PROCEDURES: Studies were identified by
      searches of the literature for reports using the terms: diabetes, insulin
      resistance, hypertension, obesity or metabolic syndrome and TNF, variants or
      polymorphism or alleles, and Nco or -308. From 824 reports, we included 31
      observational studies, case control and cohort at baseline, which analyzed the
      association between the TNFalpha polymorphism and one or more components of the
      metabolic syndrome. A fixed effect model was used to pool data from individual
      studies. RESULTS: Obesity [odds ratio, 1.23; 95% confidence interval (CI), 1.045
      to 1.45; p = 0.013] in a total of 3562 individuals from eight homogeneous
      studies, systolic arterial blood pressure (standardized difference, 0.132; 95%
      CI, 0.016 to 0.25; p < 0.03) in a total of 1624 individuals from four homogeneous
      studies and plasma insulin levels (standardized difference, 0.095; 95% CI, 0.020
      to 0.17; p = 0.013) in a total of 3720 subjects from 16 homogeneous studies were
      positively associated with the -308A variant. DISCUSSION: These results indicate
      that individuals who carried the -308A TNFalpha gene variant are at 23% risk of
      developing obesity compared with controls and showed significantly higher
      systolic arterial blood pressure and plasma insulin levels, supporting the
      hypothesis that the TNFalpha gene is involved in the pathogenesis of the
      metabolic syndrome.

PMID- 16421347
TI  - The APOA4 Thr347->Ser347 polymorphism is not a major risk factor of obesity.
AB  - OBJECTIVE: The goal of this study was to assess the association between the APOA4
      Thr(347)-->Ser(347) polymorphism and BMI and obesity. RESEARCH METHODS AND
      PROCEDURES: Men and women (n = 3320), randomly recruited in three independent
      population surveys from the north, east, and south of France, were genotyped for
      the APOA4 Thr(347)-->Ser(347) polymorphism. RESULTS: There were 1327 overweight
      (825 men, 502 women) and 611 obese (313 men, 298 women) subjects. The prevalences
      of subjects carrying at least one Ser(347) allele (*/Ser(347)) were 36.5%, 33.8%,
      and 34.3% in controls, overweight, and obese subjects, respectively (not
      significant), and those of the Ser(347)/Ser(347) genotype were 4.5%, 3.0%, and
      2.2%, respectively (not significant). In both men and women, mean BMI and body
      weight were not significantly different among APOA4 genotypes. There was no
      evidence of heterogeneity among centers, smoking status, alcohol intake, physical
      activity, and educational level categories. In men, mean waist girth was lower in
      Ser(347)/Ser(347) (92.2 +/- 9.4 cm) than in Thr(347) carriers (95.9 +/- 10.9 cm;
      p = 0.01), and plasma triglycerides levels were lower in Ser(347) (1.41 +/- 1.04
      mM) than in Thr(347)/Thr(347) carriers (1.55 +/- 1.23 mM; p = 0.01). DISCUSSION:
      These results suggest that the APOA4 347Ser allele is not a major risk factor for
      obesity or overweight.

PMID- 16421348
TI  - Total and regional fat distribution is strongly influenced by genetic factors in
      young and elderly twins.
AB  - OBJECTIVE: Indirect estimates of obesity such as BMI seem to be strongly
      influenced by genetic factors in twins. Precise measurements of total and
      regional fat as determined by direct techniques such as DXA scan have only been
      applied in a few twin studies. The aim of the present study was to estimate the
      heritability (h(2)) of total and regional fat distribution in young and elderly
      Danish twins. RESEARCH METHODS AND PROCEDURES: Monozygotic (108) and dizygotic
      (88) twins in two age groups (25 to 32 and 58 to 66 years) underwent
      anthropometric measurements and DXA scans. Intraclass correlations and etiologic
      components of variance were estimated for total and regional fat percentages
      using biometric modeling. RESULTS: The intraclass correlations demonstrated
      higher correlations for all fat percentages among monozygotic twins as compared
      with dizygotic twins. The biometric modeling revealed a major genetic component
      (h(2)) of total (h(2)(young) = 0.83, h(2)(elderly) = 0.86) and regional fat
      percentages (trunk, h(2)(young) = 0.82, h(2)(elderly) = 0.85; lower body,
      h(2)(young) = 0.83, h(2)(elderly) = 0.81; and trunk/lower body, h(2)(young) =
      0.83, h(2)(elderly) = 0.71) in both the young and elderly twins. DISCUSSION: The
      h(2) estimates emphasize that body fat and distribution as determined by DXA scan
      are under extensive genetic control.

PMID- 16421349
TI  - Water and food consumption patterns of U.S. adults from 1999 to 2001.
AB  - OBJECTIVE: High water consumption has been proposed as an aid to weight control
      and as a means of reducing the energy density of the diet. This study examines
      the relationship between water consumption and other drinking and eating
      patterns. RESEARCH METHODS AND PROCEDURES: The National Health and Nutrition
      Examination Survey 1999 to 2001, with responses from 4755 individuals > or =18
      years of age, provides the data for this cross-sectional analysis. A cluster
      analysis was performed using z-scores of specific food and beverage consumption
      to examine patterns. A multinomial logit analysis was used to examine
      sociodemographic characteristics of each dietary pattern and to examine the
      effects of water consumption on the likelihood of consuming a non-dairy caloric
      beverage. All results were weighted to be nationally representative and
      controlled for design effects. RESULTS: Within the sample, 87% consumed water,
      with an average daily consumption of 51.9 oz (1.53 liters) per consumer. Water
      consumers drank fewer soft/fruit drinks and consumed 194 fewer calories per day.
      Water consumers (potentially a self-selected sample) consumed more fruits,
      vegetables, and low- and medium-fat dairy products. Four distinct unhealthy
      dietary patterns were found that included little or no water consumption. Older
      and more educated persons used healthier food patterns. Mexican dietary patterns
      were much healthier than dietary patterns of blacks. DISCUSSION: Water
      consumption potentially is a dietary component to be promoted, but much more must
      be understood about its role in a healthy diet. Because high water consumption is
      linked with healthier eating patterns-patterns more likely to be followed by
      higher-educated, older adults-the target of water promotion and healthy diet
      options should focus on younger and less educated adults.

PMID- 16421350
TI  - An environmental approach to obesity prevention in children: Medical College of
      Georgia FitKid Project year 1 results.
AB  - OBJECTIVE: To test the hypothesis that third grade children (mean age = 8.7, SD =
      0.5) who attended an 8-month after-school program would exhibit favorable changes
      in body composition, cardiovascular fitness, blood pressure, total cholesterol,
      and high-density lipoprotein-cholesterol compared with children in control
      condition. RESEARCH METHODS AND PROCEDURES: Subjects were 61% African-American,
      31% white, and 8% other racial background from 18 public schools. Sixty-eight
      percent were eligible for free or reduced price lunch. Percentage body fat and
      bone mineral density were assessed by DXA, cardiovascular fitness by heart rate
      response to a step test, resting blood pressure with a Dinamap, and non-fasting
      total cholesterol and high-density lipoprotein-cholesterol by finger stick. Data
      pre- and post-intervention were available for 447 children. Children in the nine
      intervention schools who attended at least 40% of the after-school sessions were
      compared with control subjects. RESULTS: Compared with the control subjects and
      after controlling for race, sex, free/reduced price lunch status, and school
      level covariates, youths in the intervention group showed a relative reduction of
      percentage body fat [-0.76 (95% confidence interval (CI), -1.42, -0.09)], a
      greater relative gain in bone mineral density [0.008 (95% CI, 0.001, 0.005)], and
      a greater relative reduction in heart rate response to the step test [-4.4 (95%
      CI, -8.2, 0.6)]. The other outcome variables showed non-significant trends in
      favor of the intervention subjects. DISCUSSION: These results are promising in
      light of the potential impact on the emerging childhood obesity epidemic. The
      Medical College of Georgia FitKid Project has the potential to be
      institutionalized because it is built on the existing infrastructure in most
      public schools in the U.S.

PMID- 16421351
TI  - Predictors of long-term weight maintenance.
AB  - OBJECTIVE: The purpose of this study was to evaluate available variables of a
      long-term weight maintenance study to investigate possible factors predisposing
      to weight regain after a period of weight loss. RESEARCH METHODS AND PROCEDURES:
      The Maastricht Weight Maintenance Study is an ongoing longitudinal study of
      healthy men and women (29 men and 62 women; 18 to 65 years of age; BMI = 30.2 +/-
      3.1 kg/m(2)). A variety of parameters were measured before and after a very-low
      energy diet and after a follow-up of at least 2 years. RESULTS: Mean weight loss
      was 7.9 +/- 3.6 kg, and percent weight regain was 113.8 +/- 98.1%. Percent BMI
      regain was negatively associated with an increase in dietary restraint (r = 
      0.47, p < 0.05). Percent weight regain was negatively correlated with baseline
      resting metabolic rate (r = -0.38, p = 0.01) and baseline fat mass (r = -0.24, p
      = 0.05) and positively correlated with the magnitude of change in body weight
      (BW) expressed as maximum amplitude of BW (r = 0.21, p < 0.05). In addition,
      amplitude of BW was positively correlated with the frequency of dieting (r =
      0.57, p < 0.01). DISCUSSION: The best predictors for weight maintenance after
      weight loss were an increase in dietary restraint during weight loss, a high
      baseline resting metabolic rate, a relatively high baseline fat mass favoring a
      fat-free mass-sparing effect during weight loss, a rather stable BW, and a low
      frequency of dieting. Therefore, BW maintenance after BW loss seems to be a
      multifactorial issue, including mechanisms that regulate an individuals' energy
      expenditure, body composition, and eating behavior in such a way that energy
      homeostasis is maintained.

PMID- 16421352
TI  - Body weight and health status: importance of socioeconomic position and working
      conditions.
AB  - OBJECTIVE: To examine the association between relative body weight and health
      status and the potential modifying effects of socioeconomic position and working
      conditions on this association. RESEARCH METHODS AND PROCEDURES: The data were
      derived from three identical cross-sectional surveys conducted in 2000, 2001, and
      2002. Respondents to postal surveys were middle-aged employees of the City of
      Helsinki (7148 women and 1799 men, response rate 67%). BMI was based on self
      reported weight and height. Health status was measured by the Short-Form 36
      subscales and component summaries. RESULTS: Body weight was inversely associated
      with physical health, but in mental health, differences between BMI categories
      were small and inconsistent. In women, physical health deteriorated monotonically
      with increasing BMI, whereas in men, poor physical health was found among the
      obese only. Socioeconomic position did not modify the association between BMI and
      health. In women, the association between body weight and physical health became
      stronger with decreasing job control and increasing physical work load, whereas
      in men, a similar modifying effect was found for high job demands. DISCUSSION:
      Body weight was associated with physical health only. Lower levels of relative
      weight in women than in men may be associated with poor physical health. High
      body weight combined with adverse working conditions may impose a double burden
      on physical health.

PMID- 16421353
TI  - Trends in height and BMI of 6-year-old children during the nutrition transition
      in Chile.
AB  - OBJECTIVE: We analyzed trends in height and BMI and their interaction in 6-year
      old Chilean children over the last 15 years. RESEARCH METHODS AND PROCEDURES: We
      calculated height for age z-score (HAZ), BMI z-score, prevalence of obesity,
      underweight, and stunting from cross-sectional national school-based annual
      population surveys in 1987, 1990, 1993, 1996, 2000, and 2002. Using mixed model
      analysis, we determined the risk of obesity according to height over time as odds
      ratios (ORs) and 95% confidence interval and the potential influence of height
      and year of study on BMI z-score. RESULTS: Over the study period, height
      increased by 2.8 cm in boys and 2.6 cm in girls, whereas stunting declined from
      5% to 2% in both. Tallness increased by approximately 2%, BMI z-score increased
      from +0.3 to +0.65 in boys and to +0.62 in girls, and HAZ increased from -0.47 in
      boys and -0.45 in girls to 0 in 2002. Underweight declined from 4% to 3%, whereas
      obesity rose from 5% to approximately 14%. The probability of obesity among tall
      children was significantly greater than that for normal height children (OR, 2.3
      to 3.5). The lowest obesity risk was observed between -2 and -1 HAZ. The OR for
      obesity in the stunted relative to normal height children was variable, ranging
      from 1.23 to 0.65, whereas it was significant and consistently positive (1.1 to
      1.7) for boys and girls when it was compared with the lowest obesity risk
      according to height. DISCUSSION: Tallness is significantly associated with
      increased obesity risk in children, while stunting is also associated, but to a
      lesser degree.

PMID- 16421354
TI  - Stability of the association between birth weight and childhood overweight during
      the development of the obesity epidemic.
AB  - OBJECTIVE: To assess whether changes in the birth weight distribution or changes
      in the association of birth weight with the later risk of childhood overweight
      have contributed to the development of the obesity epidemic. RESEARCH METHODS AND
      PROCEDURES: A Danish population-based cohort study of 124,615 girls and 128,346
      boys (ages 6 to 13 years), born between 1936 and 1983, were studied. Birth weight
      and annual measurements of height and weight were obtained from school health
      records. Overweight was defined by BMI in relation to internationally accepted
      criteria. The relative risk of being overweight by birth weight was calculated
      separately for each age, sex, and time period. RESULTS: The birth weight
      distribution remained relatively stable over time. Compared with children with a
      birth weight of 3.0 to 3.5 kg, the risk of overweight increased consistently with
      each increase in birth weight category among girls and boys and at all ages
      between 6 and 13 years. Furthermore, the association between birth weight and
      increased risk of overweight in childhood remained stable across a 48-year
      period. DISCUSSION: The increase in the prevalence of overweight could not be
      explained by time trends in the distribution of birth weight or by changes in the
      association between birth weight and the later risk of overweight over time. This
      implies that, unless the prenatal environment influences the later risk of
      overweight without increasing birth weight, the environmental influences
      contributing to the obesity epidemic in children of school age operate in the
      early postnatal period.

PMID- 16421355
TI  - Tanner staging of secondary sexual characteristics and body composition, blood
      pressure, and insulin in black girls.
AB  - OBJECTIVE: To assess Tanner staging (breast and pubic hair development) and its
      relationship to measures of body composition, blood pressure, and fasting insulin
      and glucose in young black girls. RESEARCH METHODS AND PROCEDURES: Subjects were
      138 black girls, 8 to 12 years of age, recruited from elementary schools in low
      socioeconomic status neighborhoods. Exclusion criteria included the presence of
      any acute/chronic medical conditions. Pubertal stages were assessed by one of two
      pediatricians and analyzed individually, as well as with a composite index
      (prepubertal, pubertal/premenarcheal, or pubertal/menarcheal). Glucose and
      insulin were measured after a 12-hour fast. Measures of body composition included
      height, weight, BMI, waist and hip circumferences, fat mass, fat-free soft
      tissue, bone mineral density (DXA), and visceral adipose tissue (magnetic
      resonance imaging). Resting systolic and diastolic blood pressure were measured
      by Dinamap. RESULTS: With age in the model, breast development explained
      significant proportions of the variance in height, weight, fat-free soft tissue,
      bone mineral density, and insulin. Adding pubic hair development or menarche to
      those models did not significantly increase the proportion of variance that was
      explained by breast development. Furthermore, using a composite index of pubertal
      staging explained a smaller proportion of the variance compared with breast
      development alone. DISCUSSION: Combined with age, breast development was a better
      predictor of body composition and fasting insulin than was pubic hair development
      or a composite index of pubertal staging.

PMID- 16421356
TI  - Gastric bypass as treatment for obesity: trends, characteristics, and
      complications.
AB  - OBJECTIVE: This paper describes national trends in gastric bypass procedures from
      1998 through 2003 and explores the demographic and health profile of those who
      receive this procedure. Short-term outcomes such as length of stay and in
      hospital complication rates are also examined. RESEARCH METHODS AND PROCEDURES:
      Data on obese hospital inpatients who had gastric bypass were obtained from the
      1998 to 2003 National Hospital Discharge Survey. Gastric bypass was reported for
      an estimated 288,000 discharges during the 6-year study period. Trends within the
      6-year period were tested using weighted regression. Characteristics of gastric
      bypass patients were compared with those of other inpatients using a chi(2) test
      of independence and the two-sided t test. RESULTS: The estimated number of
      hospital discharges with gastric bypass increased significantly, from 14,000 in
      1998 to 108,000 in 2003. During this period, the average length of stay declined
      by 56% from 7.2 to 3.2 days. Gastric bypass patients were primarily women (84%),
      25 to 54 years of age (82%), and privately insured (76%). A 1 in 10 complication
      rate was found for discharges with gastric bypass. DISCUSSION: Gastric bypass
      procedures in the United States have increased rapidly since 1998, whereas the
      average hospital stay has decreased. The decreasing length of stay needs to be
      evaluated in conjunction with potential complication rates and the permanent
      change in anatomy and lifestyle that must accompany this procedure. Monitoring
      trends in use of this procedure is important, especially if reimbursement
      policies change and the epidemic of obesity continues.

PMID- 16421357
TI  - Heritability of body fat using DXA.

PMID- 16421361
TI  - Images in clinical medicine. Heavy-metal meals of mercury.

PMID- 16421362
TI  - Noma--the ulcer of extreme poverty.

PMID- 16421363
TI  - Crisis in Niger--outpatient care for severe acute malnutrition.

PMID- 16421364
TI  - A controlled trial of long-term inhaled hypertonic saline in patients with cystic
      fibrosis.
AB  - BACKGROUND: Inhaled hypertonic saline acutely increases mucociliary clearance
      and, in short-term trials, improves lung function in people with cystic fibrosis.
      We tested the safety and efficacy of inhaled hypertonic saline in a long-term
      trial. METHODS: In this double-blind, parallel-group trial, 164 patients with
      stable cystic fibrosis who were at least six years old were randomly assigned to
      inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent (control) saline
      twice daily for 48 weeks, with quinine sulfate (0.25 mg per milliliter) added to
      each solution to mask the taste. A bronchodilator was given before each dose, and
      other standard therapies were continued during the trial. RESULTS: The primary
      outcome measure, the rate of change (slope) in lung function (reflected by the
      forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and
      forced expiratory flow at 25 to 75 percent of FVC [FEF25-75]) during the 48 weeks
      of treatment, did not differ significantly between groups (P=0.79). However, the
      absolute difference in lung function between groups was significant (P=0.03) when
      averaged across all post-randomization visits in the 48-week treatment period. As
      compared with the control group, the hypertonic-saline group had significantly
      higher FVC (by 82 ml; 95 percent confidence interval, 12 to 153) and FEV1 (by 68
      ml; 95 percent confidence interval, 3 to 132) values, but similar FEF25-75
      values. The hypertonic-saline group also had significantly fewer pulmonary
      exacerbations (relative reduction, 56 percent; P=0.02) and a significantly higher
      percentage of patients without exacerbations (76 percent, as compared with 62
      percent in the control group; P=0.03). Hypertonic saline was not associated with
      worsening bacterial infection or inflammation. CONCLUSIONS: Hypertonic saline
      preceded by a bronchodilator is an inexpensive, safe, and effective additional
      therapy for patients with cystic fibrosis. (ClinicalTrials.gov number,
      NCT00271310.)

PMID- 16421365
TI  - Mucus clearance and lung function in cystic fibrosis with hypertonic saline.
AB  - BACKGROUND: Abnormal homeostasis of the volume of airway surface liquid in
      patients with cystic fibrosis is thought to produce defects in mucus clearance
      and airway defense. Through osmotic forces, hypertonic saline may increase the
      volume of airway surface liquid, restore mucus clearance, and improve lung
      function. METHODS: A total of 24 patients with cystic fibrosis were randomly
      assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent
      sodium chloride) four times daily with or without pretreatment with amiloride.
      Mucus clearance and lung function were measured during 14-day baseline and
      treatment periods. RESULTS: Long-term inhalation of hypertonic saline without
      pretreatment with amiloride (i.e., with placebo pretreatment) resulted in a
      sustained (> or =8 hours) increase in 1-hour rates of mucus clearance, as
      compared with those with amiloride pretreatment (14.0+/-2.0 vs. 7.0+/-1.5
      percent, respectively; P=0.02) and increased 24-hour rates of mucus clearance
      over baseline. Furthermore, inhalation of hypertonic saline with placebo improved
      the forced expiratory volume in one second (FEV1) between the baseline period and
      the treatment period (mean difference, 6.62 percent; 95 percent confidence
      interval, 1.6 to 11.7; P=0.02), whereas hypertonic saline with amiloride did not
      improve FEV1 (mean difference, 2.9 percent; 95 percent confidence interval, -2.2
      to 8.0; P=0.23). Forced vital capacity (FVC), the forced expiratory flow between
      25 and 75 percent of FVC (FEF25-75), and respiratory symptoms also significantly
      improved in patients treated with hypertonic saline and placebo, whereas the
      residual volume as a proportion of total lung capacity (RV:TLC) did not change in
      either group. A comparison of the changes in lung function in the two groups
      showed no significant difference. In vitro data suggested that sustained
      hydration of airway surfaces was responsible for the sustained improvement in
      mucus clearance, whereas inhibition of osmotically driven water transport by
      amiloride accounted for the observed loss of clinical benefit. CONCLUSIONS: In
      patients with cystic fibrosis, inhalation of hypertonic saline produced a
      sustained acceleration of mucus clearance and improved lung function. This
      treatment may protect the lung from insults that reduce mucus clearance and
      produce lung disease.

PMID- 16421366
TI  - Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and
      efavirenz for HIV.
AB  - BACKGROUND: Durable suppression of replication of the human immunodeficiency
      virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens
      to which patients can easily adhere. METHODS: We conducted an open-label,
      noninferiority study involving 517 patients with HIV infection who had not
      previously received antiretroviral therapy and who were randomly assigned to
      receive either a regimen of tenofovir disoproxil fumarate (DF), emtricitabine,
      and efavirenz once daily (tenofovir-emtricitabine group) or a regimen of fixed
      dose zidovudine and lamivudine twice daily plus efavirenz once daily (zidovudine
      lamivudine group). The primary end point was the proportion of patients without
      baseline resistance to efavirenz in whom the HIV RNA level was less than 400
      copies per milliliter at week 48 of the study. RESULTS: Through week 48,
      significantly more patients in the tenofovir-emtricitabine group reached and
      maintained the primary end point of less than 400 copies of HIV RNA per
      milliliter than did those in the zidovudine-lamivudine group (84 percent vs. 73
      percent, respectively; 95 percent confidence interval for the difference, 4 to 19
      percent; P=0.002). This difference excludes the inferiority of the tenofovir DF,
      emtricitabine, and efavirenz regimen, indicating a significantly greater response
      with this regimen. Significant differences were also seen in the proportion of
      patients with HIV RNA levels of less than 50 copies per milliliter (80 percent in
      the tenofovir-emtricitabine group vs. 70 percent in the zidovudine-lamivudine
      group; 95 percent confidence interval for the difference, 2 to 17 percent;
      P=0.02) and in increases in CD4 cell counts (190 vs. 158 cells per cubic
      millimeter, respectively; 95 percent confidence interval for the difference, 9 to
      55; P=0.002). More patients in the zidovudine-lamivudine group than in the
      tenofovir-emtricitabine group had adverse events resulting in discontinuation of
      the study drugs (9 percent vs. 4 percent, respectively; P=0.02). In none of the
      patients did the K65R mutation develop. CONCLUSIONS: Through week 48, the
      combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the
      criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus
      efavirenz and proved superior in terms of virologic suppression, CD4 response,
      and adverse events resulting in discontinuation of the study drugs.
      (ClinicalTrials.gov number, NCT00112047.)

PMID- 16421367
TI  - Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch
      syndrome.
AB  - BACKGROUND: Women with the Lynch syndrome (hereditary nonpolyposis colorectal
      cancer) have a 40 to 60 percent lifetime risk of endometrial cancer and a 10 to
      12 percent lifetime risk of ovarian cancer. The benefit of prophylactic
      gynecologic surgery for women with this syndrome has been uncertain. We designed
      this study to determine the reduction in the risk of gynecologic cancers
      associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in
      women with the Lynch syndrome. METHODS: Three hundred fifteen women with
      documented germ-line mutations associated with the Lynch syndrome were
      identified. Women who had undergone prophylactic hysterectomy (61 women) and
      women who had undergone prophylactic bilateral salpingo-oophorectomy (47 women)
      were matched with mutation-positive women who had not undergone the procedure in
      question (210 women for the analysis of endometrial cancer and 223 for the
      analysis of ovarian cancer). Women who had undergone prophylactic surgery and
      their matched controls were followed from the date of the surgery until the
      occurrence of cancer or until the data were censored at the time of the last
      follow-up visit. RESULTS: There were no occurrences of endometrial, ovarian, or
      primary peritoneal cancer among the women who had undergone prophylactic surgery.
      Endometrial cancer was diagnosed in 69 women in the control group (33 percent),
      for an incidence density of 0.045 per woman-year, yielding a prevented fraction
      (the proportion of potential new cancers prevented) of 100 percent (95 percent
      confidence interval, 90 to 100 percent). Ovarian cancer was diagnosed in 12 women
      in the control group (5 percent), for an incidence density of 0.005 per woman
      year, yielding a prevented fraction of 100 percent (95 percent confidence
      interval, -62 to 100 percent). CONCLUSIONS: These findings suggest that
      prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective
      strategy for preventing endometrial and ovarian cancer in women with the Lynch
      syndrome.

PMID- 16421369
TI  - Images in clinical medicine. Bleeding angiodysplasia in the duodenum.

PMID- 16421368
TI  - Estrogen carcinogenesis in breast cancer.

PMID- 16421370
TI  - Case records of the Massachusetts General Hospital. Case 2-2006. A 31-year-old,
      HIV-positive man with rectal pain.

PMID- 16421371
TI  - Restoring airway surface liquid in cystic fibrosis.

PMID- 16421372
TI  - Reducing the risk of gynecologic cancer in the Lynch syndrome.

PMID- 16421373
TI  - Disarming pathogens--a new approach for antibiotic development.

PMID- 16421374
TI  - Antipsychotic drugs and schizophrenia.

PMID- 16421375
TI  - Vasodilators in aortic regurgitation.

PMID- 16421376
TI  - Childhood growth and coronary events.

PMID- 16421377
TI  - Asbestos exposure and serum osteopontin.

PMID- 16421378
TI  - Malignant mesothelioma.

PMID- 16421379
TI  - Immunologic tolerance to intravenously injected insulin.

PMID- 16421380
TI  - Double duty.

PMID- 16421381
TI  - Dividing to keep muscle together: the role of satellite cells in aging skeletal
      muscle.
AB  - The factors responsible for the atrophy of skeletal muscle with aging remain to
      be elucidated. Recent evidence points toward an important role for a population
      of cells located on the surface of skeletal muscle fibers, known as satellite
      cells, in maintaining the integrity of skeletal myocytes throughout the life
      span. This Perspective examines the role that these cells are thought to play in
      aging muscle atrophy, and highlights a recent study by Brack and colleagues that
      attempts to understand the role of satellite cells in maintaining the ratio of
      myonuclear number to cytoplasmic volume within myocytes as we age.

PMID- 16421383
TI  - Congenital anomalies in the offspring of military personnel?

PMID- 16421384
TI  - Micro-epidemiology of the healthy worker effect?

PMID- 16421385
TI  - Acute effects of force and vibration on finger blood flow.
AB  - OBJECTIVES: To investigate the effects of contact force at the finger on acute
      changes in finger circulation during exposure to vibration. METHODS: Each of 10
      subjects attended 11 sessions in which they experienced five successive
      experimental 5-minute periods: (i) no force and no vibration; (ii) force and no
      vibration; (iii) force and vibration; (iv) force and no vibration; (v) no force
      and no vibration. During periods (ii) to (iv), the intermediate phalanx of the
      right middle finger applied one of two forces (2 N or 5 N) on a platform that
      vibrated during period (iii) at one of two frequencies: 31.5 Hz (at 4 or 16 ms(
      2) r.m.s.) or 125 Hz (at 16 or 64 ms(-2) r.m.s.). Finger blood flow was measured
      in the exposed right middle finger, the unexposed right little finger, and the
      unexposed left middle fingers throughout the 25 minutes of each session. RESULTS:
      The application of force alone caused a reduction in finger blood flow in the
      exposed finger, but not other fingers. There were additional reductions in finger
      blood flow caused by vibration, with greater reductions at the higher vibration
      magnitudes at both frequencies but no difference between the two frequencies when
      using unweighted acceleration. The vibration caused a similar vasoconstriction in
      vibrated and non-vibrated fingers. CONCLUSIONS: Modest levels of force applied by
      a finger can have a large effect on the finger blood flow, possibly due to the
      constriction of local blood vessels. The acute vascular effects of vibration
      cause additional reductions in finger blood flow that are not limited to the
      finger experiencing force and vibration. In all fingers (exposed and not exposed
      to vibration), the greater the magnitude of vibration, the greater the reduction
      in finger blood flow. In all fingers (exposed and not exposed to vibration), when
      the vibration was frequency weighted according to current standards, 125 Hz
      vibration caused greater reductions in finger blood flow than 31.5 Hz vibration.

PMID- 16421386
TI  - A higher risk of congenital anomalies in the offspring of personnel who served
      aboard a Norwegian missile torpedo boat.
AB  - BACKGROUND: In the 1990s, congenital anomalies were reported among children whose
      fathers had served aboard a Norwegian missile torpedo boat (MTB). The Royal
      Norwegian Navy asked the University of Bergen to look into this problem as one
      part of a general health and work environment surveillance. AIMS: To estimate any
      increased risk of having children with congenital anomalies and having stillborn
      children among the offspring of workers that had served aboard the MTB and to
      investigate possible differences in exposure and other risk factors between these
      groups. METHODS: Data from a cross-sectional study among all current employees of
      the Norwegian Navy (n = 2265, response rate 58%) were analysed. RESULTS: The
      prevalence ratio of having a child with congenital malformations associated with
      working on the ship was 4.0 (95% CI 1.9 to 8.6). The prevalence ratio of having a
      child who was stillborn or died within one week was 4.1 (95% CI 1.7 to 9.9).
      CONCLUSION: Service aboard the MTB was associated with an increased risk of
      having children with congenital birth defects and having children that were
      stillborn. The causes of these findings are unknown.

PMID- 16421387
TI  - Burnout as a predictor of self-reported sickness absence among human service
      workers: prospective findings from three year follow up of the PUMA study.
AB  - AIM: To investigate whether burnout predicts sickness absence days and sickness
      absence spells in human service workers. METHOD: A total of 824 participants from
      an ongoing prospective study in different human service sector organisations were
      eligible for the three year follow up analysis. Burnout was measured with the
      work related burnout scale of the Copenhagen Burnout Inventory. Sickness absence
      was measured with self-reported number of days and spells during the last 12
      months before the baseline and the follow up survey. A Poisson regression model
      with a scale parameter was used to account for over dispersion. A linear
      regression model was used for analysing changes in burnout and absence between
      baseline and follow up. RESULTS: Burnout was prospectively associated with both
      sickness absence days and sickness absence spells per year. Differences in
      sickness absence days varied from a mean of 5.4 days per year in the lowest
      quartile of the work related burnout scale to a mean of 13.6 in the highest
      quartile. An increase of one standard deviation on the work related burnout scale
      predicted an increase of 21% in sickness absence days per year (rate ratio 1.21,
      95% CI 1.11 to 1.32) after adjusting for gender, age, organisation, socioeconomic
      status, lifestyle factors, family status, having children under 7 years of age,
      and prevalence of diseases. Regarding sickness absence spells, an increase of one
      standard deviation on the work related burnout scale predicted an increase of 9%
      per year (rate ratio 1.09, 95% CI 1.02 to 1.17). Changes in burnout level from
      baseline to follow up were positively associated with changes in sickness absence
      days (estimate 1.94 days/year, SE 0.63) and sickness absence spell (estimate 0.34
      spells/year, SE 0.08). CONCLUSION: The findings indicate that burnout predicts
      sickness absence. Reducing burnout is likely to reduce sickness absence.

PMID- 16421388
TI  - Airborne occupational exposures and risk of oesophageal and cardia
      adenocarcinoma.
AB  - BACKGROUND: The reasons for the increasing incidence of and strong male
      predominance in patients with oesophageal and cardia adenocarcinoma remain
      unclear. The authors hypothesised that airborne occupational exposures in male
      dominated industries might contribute. METHODS: In a nationwide Swedish
      population based case control study, 189 and 262 cases of oesophageal and cardia
      adenocarcinoma respectively, 167 cases of oesophageal squamous cell carcinoma,
      and 820 frequency matched controls underwent personal interviews. Based on each
      study participant's lifetime occupational history the authors assessed cumulative
      airborne occupational exposure for 10 agents, analysed individually and combined,
      by a deterministic additive model including probability, frequency, and
      intensity. Furthermore, occupations and industries of longest duration were
      analysed. Relative risks were estimated by odds ratios (OR), with 95% confidence
      intervals (CI), using conditional logistic regression, adjusted for potential
      confounders. RESULTS: Tendencies of positive associations were found between high
      exposure to pesticides and risk of oesophageal (OR 2.3 (95% CI 0.9 to 5.7)) and
      cardia adenocarcinoma (OR 2.1 (95% CI 1.0 to 4.6)). Among workers highly exposed
      to particular agents, a tendency of an increased risk of oesophageal squamous
      cell carcinoma was found. There was a twofold increased risk of oesophageal
      squamous cell carcinoma among concrete and construction workers (OR 2.2 (95% CI
      1.1 to 4.2)) and a nearly fourfold increased risk of cardia adenocarcinoma among
      workers within the motor vehicle industry (OR 3.9 (95% CI 1.5 to 10.4)). An
      increased risk of oesophageal squamous cell carcinoma (OR 3.9 (95% CI 1.2 to
      12.5)), and a tendency of an increased risk of cardia adenocarcinoma (OR 2.8 (95%
      CI 0.9 to 8.5)), were identified among hotel and restaurant workers. CONCLUSIONS:
      Specific airborne occupational exposures do not seem to be of major importance in
      the aetiology of oesophageal or cardia adenocarcinoma and are unlikely to
      contribute to the increasing incidence or the male predominance.

PMID- 16421389
TI  - Promoting excellent work ability and preventing poor work ability: the same
      determinants? Results from the Swedish HAKuL study.
AB  - AIM: Health has been described as a continuum between the two poles of excellent
      health and ill health. Research has so far focused on the negative pole, leaving
      knowledge about the positive pole vague. With a main focus on working life, the
      authors aim was to identify determinants promoting excellent work ability and
      determinants preventing poor work ability. METHODS: 5638 (73% answering rate)
      employees in the public sector in Sweden answered a questionnaire both at
      baseline and at follow up 18 months later. The employees were divided into three
      groups based on sick leave at follow up: excellent work ability (13%), poor work
      ability (15%), and a middle group (72%). Self reported sociodemographic data,
      lifestyle data, and working life exposures at baseline were fitted into logistic
      regression models to determine which factors, if any, promoted excellent work
      ability or protected against poor work ability. RESULTS: Some determinants were
      mutual, but more than half of the determinants in the final model were associated
      solely with promoting excellent work ability or preventing poor work ability,
      thus creating different patterns of associations. Promotion of excellent work
      ability seemed more dependent on physical factors, clear work tasks, and positive
      feedback, while prevention of poor work ability seemed more dependent on job
      security and psychosocial factors. CONCLUSIONS: This explorative longitudinal
      study showed slightly different patterns of determinants promoting excellent work
      ability and preventing poor work ability. As most of the identified determinants
      are amenable to influence, our results open up the possibility of interventions
      for promoting excellent work ability and preventing poor work ability.

PMID- 16421390
TI  - Latex allergy: a follow up study of 1040 healthcare workers.
AB  - BACKGROUND: Natural rubber latex allergy can cause skin and respiratory symptoms
      The aim of this study was to evaluate the prevalence and incidence of latex
      related symptoms and sensitisation among a large group of healthcare workers in
      Trieste hospitals, followed for three years before and after the introduction of
      powder-free gloves with low latex release. METHODS: In the years 1997-99 the
      authors evaluated 1040 healthcare workers exposed to latex allergen for latex
      related symptoms and sensitisation by means of a questionnaire, a medical
      examination, skin prick tests, and IgE specific antibody assay. The second
      evaluation was carried out in the years 2000-02, subsequent to the changeover to
      a powder-free environment. RESULTS: Glove related symptoms were seen in 21.8% of
      the nurses (227), mostly consisting of mild dermatitis: 38 (3.6%) complaining of
      contact urticaria and 24 (2.3%) of asthma and/or rhinitis. These symptoms were
      significantly related to skin prick tests positive to latex (OR = 9.70; 95% CI
      5.5 to 17) and to personal atopy (OR = 2.29; 95% CI 1.6 to 3.2). Follow up was
      completed in 960 subjects (92.3%): 19 new subjects (2.4%) complained of itching
      erythema when using gloves, but none was prick positive to latex. Symptoms
      significantly improved and in most cases disappeared (p<0.0001). CONCLUSIONS:
      Simple measures such as the avoidance of unnecessary glove use, the use of non
      powdered latex gloves by all workers, and use of non-latex gloves by sensitised
      subjects can stop the progression of latex symptoms and can avoid new cases of
      sensitisation.

PMID- 16421391
TI  - Predictors of early leaving from the cotton spinning mill environment in newly
      hired workers.
AB  - OBJECTIVE: This longitudinal study aimed to identify the predictors of leaving
      during the first year of employment from the cotton spinning mill environment in
      newly hired workers. METHODS: One hundred and ninety eight consecutively
      appointed new employees were investigated by questionnaire, lung function test,
      and skin test. They were examined before employment and at the end of the 1st
      week, and the 1st, 3rd, 6th, and 12th month after starting work and when possible
      before leaving their job. 572 personal dust sampling and 191 endotoxin
      measurements were performed to assess the environmental exposure. For the
      univariate analysis chi2, Student t tests, ANOVA, and Kruskall Wallis tests were
      used. Cox proportional hazards analysis was used to identify factors associated
      with leaving the job. RESULTS: Fifty three per cent of workers left the mill
      environment during their first working year. Work related lower respiratory tract
      symptoms reported at the third month were associated with an increase rate of
      leaving the industry compared to those remaining in the industry (25% v 4.8%;
      p<0.005). Having respiratory symptoms at the first month of work predicted those
      leaving the industry at some point in the next 11 months. According to the Cox
      model, increasing age and having work related lower respiratory tract symptoms
      were found to be predictors for leaving job at the first working year. Atopic
      status, dust and endotoxin levels, and lung function changes were not
      consistently predictive of workers who left the industry in the follow up period.
      CONCLUSION: This study demonstrated that work related respiratory symptoms can
      predict workers likely to leave the cotton mill environment during the first year
      of employment, but atopy or acute lung function changes do not.

PMID- 16421392
TI  - Household exposure to pesticides and risk of childhood acute leukaemia.
AB  - OBJECTIVES: To investigate the relation between childhood acute leukaemia and
      household exposure to pesticides. METHODS: The study included 280 incident cases
      of acute leukaemia and 288 controls frequency matched on gender, age, hospital,
      and ethnic origin. The data were obtained from standardised face to face
      interviews of the mothers with detailed questions on parental occupational
      history, home and garden insecticide use, and insecticidal treatment of
      pediculosis. Odds ratios were estimated using unconditional regression models
      including the stratification variables parental socioeconomic status and housing
      characteristics. RESULTS: Acute leukaemia was observed to be significantly
      associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI
      1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden
      insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95%
      CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis
      was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3).
      CONCLUSION: The results reported herein support the hypothesis that various types
      of insecticide exposure may be a risk factor for childhood acute leukaemia. The
      observed association with insecticidal shampoo treatment of pediculosis, which
      has never been investigated before, requires further study.

PMID- 16421393
TI  - Parkinson's disease and other basal ganglia or movement disorders in a large
      nationwide cohort of Swedish welders.
AB  - INTRODUCTION: Although it has been hypothesised that metal welding and flame
      cutting are associated with an increased risk for Parkinson's disease due to
      manganese released in the welding fume, few rigorous cohort studies have
      evaluated this risk. METHODS: The authors examined the relation between
      employment as a welder and all basal ganglia and movement disorders (ICD-10, G20
      26) in Sweden using nationwide and population based registers. All men recorded
      as welders or flame cutters (n = 49,488) in the 1960 or 1970 Swedish National
      Census were identified and their rates of specific basal ganglia and movement
      disorders between 1964 and 2003 were compared with those in an age and
      geographical area matched general population comparison cohort of gainfully
      employed men (n = 489,572). RESULTS: The overall rate for basal ganglia and
      movement disorders combined was similar for the welders and flame cutters
      compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI
      0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99).
      Adjusted rate ratios for other individual basal ganglia and movement disorders
      were also not significantly increased or decreased. Further analyses of
      Parkinson's disease by attained age, time period of follow up, geographical area
      of residency, and educational level revealed no significant differences between
      the welders and the general population. Rates for Parkinson's disease among
      welders in shipyards, where exposures to welding fumes are higher, were also
      similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). CONCLUSION:
      This nationwide record linkage study offers no support for a relation between
      welding and Parkinson's disease or any other specific basal ganglia and movement
      disorders.

PMID- 16421394
TI  - Organisational injustice and impaired cardiovascular regulation among female
      employees.
AB  - OBJECTIVES: To examine the relation between perceived organisational justice and
      cardiovascular reactivity in women. METHODS: The participants were 57 women
      working in long term care homes. Heart rate variability and systolic arterial
      pressure variability were used as markers of autonomic function. Organisational
      justice was measured using the scale of Moorman. Data on other risk factors were
      also collected. RESULTS: Results from logistic regression models showed that the
      risk for increased low frequency band systolic arterial pressure variability was
      3.8-5.8 times higher in employees with low justice than in employees with high
      justice. Low perceived justice was also related to an 80% excess risk of reduced
      high frequency heart rate variability compared to high perceived justice, but
      this association was not statistically significant. CONCLUSIONS: These findings
      are consistent with the hypothesis that cardiac dysregulation is one stress
      mechanism through which a low perceived justice of decision making procedures and
      interpersonal treatment increases the risk of health problems in personnel.

PMID- 16421395
TI  - World at work: Dental laboratory technicians.

PMID- 16421396
TI  - The health hazards of volcanoes and geothermal areas.

PMID- 16421397
TI  - The President's Conference 2005: "Technology in Imaging and Radiotherapy--towards
      improved workflow and productivity".

PMID- 16421398
TI  - CT scanning the early days.
AB  - CT scanning has become an established diagnostic tool within the radiology
      department. This article covers some of the history of the development and early
      days of CT scanning. It is based upon the lecture given on the Memorial Day for
      Sir Godfrey Hounsfield during the British Institute of Radiology President's
      Conference 2005.

PMID- 16421399
TI  - Cardiac applications of multislice computed tomography.

PMID- 16421400
TI  - Technology solutions for better outcomes: integrated information management in
      key to productivity increases in medicine.
AB  - The challenges to healthcare systems around the world are primarily impacted by
      two topics: demographic factors and progress in medicine. An ageing population
      inherently needs more medical services which add financial burdens, in
      particular, to public healthcare. Since the level of medical education is growing
      at the same time, we are observing an increased demand for sophisticated (in
      general expensive) medicine. Drastic changes in financing seem unavoidable.
      Multiple diagnoses, repeated examinations, trial-and-error, overcapacities and
      other signs of missing economical considerations are reinforced by reimbursement
      systems. In a world where, in principle, all information is available everywhere,
      more than a patient's history should be accessible. Other industries have
      knowledge management systems in place that make state-of-the-art expertise
      available everywhere. Intelligent patient databases could consist of learning
      cycles that (i) enable the individual to benefit from structured knowledge, in
      addition to personal experience of the physician, and (ii) use the knowledge
      generated from the individual to extend the database. The novel area of molecular
      medicine fits perfectly well into these scenarios. Only attached to an IT
      backbone can the flood of information be managed in a beneficial way. Efficiency
      improvements in healthcare address the needs of all parties in the system:
      patients, providers, and payers. The opportunities, however, can only materialize
      if everyone is prepared to change. IT will set the standards for the biggest
      challenge in healthcare: The paradigm shift in medicine.

PMID- 16421401
TI  - The case for particle therapy.
AB  - Among the most important decisions facing the British Government regarding the
      treatment of cancer in the National Health Service (NHS) is the purchase of
      charged particle therapy (CPT) centres. CPT is different from conventional
      radiotherapy: the dose is deposited far more selectively in Bragg Peaks by either
      protons or "heavy" ions, such as carbon. In this way, it is possible to "dose
      paint" targets, voxel by voxel, with far less dose to surrounding tissues than
      with X-ray techniques. At present the UK possesses a 62 MeV cyclotron proton
      facility at Clatterbridge (Wirral), which provides therapy for intraocular
      cancers such as melanoma; for deeper situated cancers in the pelvis, chest etc.,
      much higher energies, over 200 MeV are required from a synchrotron facility.
      There is an impressive expansion in particle beam therapy (PBT) centres
      worldwide, since they offer good prospects of improved quality of life with
      enhanced cancer cures in situations where conventional therapy is limited due to
      radioresistance or by the close proximity of critical normal tissues. There is a
      threat to UK Oncology, since it is anticipated that several thousand British
      patients may require referral abroad for therapy; this would severely disrupt
      their multidisciplinary management and require demanding logistical support.

PMID- 16421402
TI  - The contribution of PET/CT to improved patient management.
AB  - With the introduction of both SPET/CT and PET/CT, multimodality imaging has truly
      entered routine clinical practice. Multiple slice spiral CT scanners have been
      incorporated with multiple detector gamma cameras or PET systems, such that the
      benefit of these modalities can be achieved in one patient sitting. The subject
      of this manuscript is PET/CT and its impact on patient management. Applications
      of PET/CT span the whole field of medical and surgical oncology since very few
      cancers do not take up the labelled glucose tracer, (18)F-FDG. Given the contrast
      achieved, high-quality data can be obtained with FDG PET/CT. This technology has
      now spread worldwide and has been the subject of intense interest, as witnessed
      by the vast body of published evidence. In this short overview, only a brief
      discussion of the main clinical applications is possible. Novel applications of
      PET/CT outside the field of oncology are expected in the near future.

PMID- 16421403
TI  - Mesenteric panniculitis in oncologic patients: PET-CT findings.
AB  - The aim of this study is to assess the role of PET/CT in differentiating between
      mesenteric panniculitis (MP) and co-existing MP and mesenteric tumoural
      involvement. A total of 33 PET/CT examinations, of 19 oncologic patients (16 men
      and three women with ages ranging from 48 years to 83 years) with findings of MP
      on the CT part of the study were retrospectively reviewed. The FDG uptake in
      mesenteric nodules was recorded. The final diagnosis of malignant mesenteric
      involvement was based on clinical and imaging follow-up. Based on the FDG uptake
      in mesenteric nodules, patients were categorized as group A: increased mesenteric
      uptake (n=8) and group B: no mesenteric uptake (n=11). In seven of the eight
      patients in group A, a co-existing MP and mesenteric tumour involvement was
      found: one patient had a recurrent cervical carcinoma and the other six patients
      had lymphoma. In four of these six patients, the positive PET findings
      disappeared on follow-up PET/CT with complete remission while the CT findings of
      the MP remained unchanged. In the other two, the PET findings progressed along
      with clinical deterioration. In the last patient of group A, with rectal
      carcinoma without evidence of recurrence, the mesenteric FDG uptake was a false
      positive uptake. In all 11 patients with CT findings of MP and negative PET, no
      malignant involvement of the mesentery was diagnosed. To conclude, a negative PET
      has a high diagnostic accuracy in excluding tumoural mesenteric involvement while
      increased uptake suggests the co-existing of mesenteric deposits, particularly in
      patients with lymphoma.

PMID- 16421404
TI  - Diagnostic efficacy of SonoVue, a second generation contrast agent, in the
      assessment of extracranial carotid or peripheral arteries using colour and
      spectral Doppler ultrasound: a multicentre study.
AB  - The purpose of this study was to demonstrate the improvement in diagnostic
      quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced
      ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation
      of extracranial carotid or peripheral arteries. 82 patients with suspected
      extracranial carotid or peripheral arterial disease received four SonoVue doses
      (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and
      following each dose. Diagnostic quality of the CE-US examinations was evaluated
      off-site for duration of clinically useful contrast enhancement, artefact effects
      and percentage of examinations converted from non-diagnostic to diagnostic.
      Accuracy, sensitivity and specificity were assessed as agreement of CE-US
      diagnosis evaluated by an independent panel of experts with reference standard
      modality. The median duration of clinically useful signal enhancement
      significantly increased with increasing SonoVue doses (p< or =0.002). At the dose
      of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive
      examinations significantly improved, falling from 40.7% at baseline down to 5.1%.
      Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity
      and specificity of assessment of disease compared with baseline ultrasound.
      SonoVue increases the diagnostic quality of Doppler images and improves the
      accuracy of both spectral and colour Doppler examinations of extracranial carotid
      or peripheral arterial disease.

PMID- 16421405
TI  - Lymphoepithelioma-like carcinoma of salivary glands: treatment results and
      failure patterns.
AB  - The purpose of this study was to evaluate the treatment results and failure
      patterns of lymphoepithelioma-like carcinoma (LELC) of salivary glands. From June
      1987 to May 2001, nine patients with LELC of salivary glands were treated at our
      hospital. One patient was excluded due to the loss of clinical follow-up after
      surgery. For the remaining eight patients, the primary tumour sites were parotid
      glands (4 patients), submandibular glands (3), and the minor salivary glands in
      right cheek (1), respectively. Seven patients underwent surgical treatment and
      post-operative radiotherapy, while the other one patient was treated with surgery
      only. The total radiation dose to the salivary tumour bed ranged from 39.6 Gy to
      67.6 Gy (mean dose: 58.3 Gy and median dose: 59 Gy). The treatment results and
      failure patterns were analysed. The survival time ranged from 21.4 months to
      145.2 months (mean: 69.1 months, median: 54.5 months). At the end of follow-up,
      six patients were still alive and two died. One patient died of distant
      metastases 21.5 months after the surgical treatment of LELC. The other case died
      of intercurrent disease (pontine haemorrhage) 53 months after surgery. No patient
      had local or regional failure after the treatments. Distant failure was noted in
      two patients. The patients with LELC of salivary glands were shown to have
      favourable prognoses. No local or regional failure was noted. However, distant
      failure developed in two patients. The risk of distant metastasis should be
      carefully monitored, especially for those patients with more advanced neck node
      involvement.

PMID- 16421406
TI  - Comparison of patient doses in 256-slice CT and 16-slice CT scanners.
AB  - The 256-slice CT-scanner has been developed at the National Institute of
      Radiological Sciences. Nominal beam width was 128 mm in the longitudinal
      direction. When scanning continuously at the same position to obtain four
      dimensional (4D) images, the effective dose is increased in proportion to the
      scan time. Our purpose in this work was to measure the dose for the 256-slice CT,
      to compare it with that of the 16-slice CT-scanner, and to make a preliminary
      assessment of dose for dynamic 3D imaging (volumetric cine imaging). Our group
      reported previously that the phantom length and integration range for dosimetry
      needed to be at least 300 mm to represent more than 90% of the line integral dose
      with the beam width between 20 mm and 138 mm. In order to obtain good estimates
      of the dose, we measured the line-integral dose over a 300 mm range in PMMA
      (polymethylmethacrylate) phantoms of 160 mm or 320 mm diameter and 300 mm length.
      Doses for both CT systems were compared for a clinical protocol. The results
      showed that the 256-slice CT generates a smaller dose than the 16-slice CT in all
      examinations. For volumetric cine imaging, we found an acceptable scan time would
      be 6 s to 11 s, depending on examinations, if dose must be limited to the same
      values as routine examinations with a conventional multidetector CT. Finally, we
      discussed the studies necessary to make full use of volumetric cine imaging.

PMID- 16421407
TI  - Assessment of tube current modulation in pelvic CT.
AB  - An anatomically shaped polymethylmethacrylate (PMMA) phantom was used to assess
      the effect of the Siemens CARE Dose mA modulation system on pelvic CT scans. The
      effect of the system on absorbed dose to air, image percentage noise and the
      signal to noise ratio of clinically relevant details was assessed. The signal to
      noise ratio was calculated using Polytetrafluoroethylene (PTFE) and distilled
      water inserts; PTFE was used to represent bony structure and distilled water was
      used to represent soft tissue abscess. Pelvis protocols identified from local
      hospitals and the UK CT Dose Survey (2002), were assessed and compared with those
      provided by Siemens Medical (UK). These protocols were tested on a Siemens
      Sensation 4 CT scanner, both with and without CARE Dose. Results were obtained
      which showed that dose savings were possible with no significant increase in
      image noise. Dose reductions were 8% in the lateral positions in the phantom and
      42% in the centre, top and bottom. The calculated "CTDIvol" was 32% lower with
      CARE Dose than without CARE Dose. This is slightly greater than the 25% change in
      the effective mAs values that was found. This implies that the reduction in the
      effective mAs values is a reasonable predictor of the total reduction in absorbed
      dose to air, whilst slightly underestimating the actual change. The results also
      showed a non-significant trend towards decreased signal to noise ratios for
      clinically relevant CT numbers when CARE Dose was activated. This suggests that
      tube current modulation may detrimentally affect signal detection due to changes
      in image noise.

PMID- 16421408
TI  - Radiosurgical palliation of aggressive murine SCCVII squamous cell carcinomas
      using synchrotron-generated X-ray microbeams.
AB  - Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy
      (MRT), was tested at the European Synchrotron Radiation Facility (ESRF). The left
      tibiofibular thigh of a mouse bearing a subcutaneously (sc) implanted mouse model
      (SCCVII) of aggressive human squamous-cell carcinoma was irradiated in two
      orthogonal exposures with or without a 16 mm aluminium filter through a multislit
      collimator (MSC) by arrays of nearly parallel microbeams spaced 200 microm on
      centre (oc). The peak skin-entrance dose from each exposure was 442 Gy, 625 Gy,
      or 884 Gy from 35 microm wide beams or 442 Gy from 70 microm wide beams. The
      442/35, 625/35, 884/35 and 442/70 MBRSs yielded 25 day, 29 day, 37 day and 35 day
      median survival times (MST) (post-irradiation), respectively, exceeding the 20
      day MST from 35 Gy-irradiation of SCCVIIs with a seamless 100 kVp X-ray beam.

PMID- 16421409
TI  - Solitary pulmonary nodule with growth and contrast enhancement at CT:
      inflammatory pseudotumour as an unusual benign cause.
AB  - Small (< or =10 mm) pulmonary nodules are frequently detected at modern chest CT.
      As most of these nodules are benign, non-invasive classification is required-
      usually based on assessment of growth and perfusion. Absence of growth and no
      evidence of perfusion, as demonstrated by lack of enhancement at contrast
      enhanced CT or MRI, strongly suggest a benign nodule. On the other hand, growth
      with a doubling of the nodule's volume between 20 days and 400 days or
      enhancement suggest a malignant nature of the lesion. We present an example of a
      nodule with strong contrast enhancement and a doubling time of approximately 260
      days, which histologically represented a benign inflammatory pseudotumour.

PMID- 16421410
TI  - Non-haemorrhagic subdural collection complicating rupture of a middle cranial
      fossa arachnoid cyst.
AB  - Arachnoid cysts are a common incidental finding on routine brain imaging and, for
      the most part, their presence is uneventful. Occasionally they may be associated
      with haemorrhage into the subdural compartment. Rarer still is simple rupture of
      the contents of the arachnoid cyst into the extra-axial space. MRI can help
      distinguish between these two rare occurrences--an important distinction to make
      as this may assist in directing the treating clinician toward the most
      appropriate management plan.

PMID- 16421411
TI  - Social factors in improving radiological perception.

PMID- 16421412
TI  - The Grandfather of volume scanning.

PMID- 16421413
TI  - A deformed skull with enlarging hand and feet in a young female.

PMID- 16421414
TI  - Poor outcome with front-line autologous transplantation in t(4;14) multiple
      myeloma: low complete remission rate and short duration of remission.

PMID- 16421415
TI  - Correlates of return to work for breast cancer survivors.
AB  - PURPOSE: To identify correlates of return to work for employed breast cancer
      survivors. PATIENTS AND METHODS: Patients included 416 employed women with newly
      diagnosed breast cancer identified from the Metropolitan Detroit Cancer
      Surveillance System. Patients were interviewed by telephone 12 and 18 months
      after diagnosis. Correlates of return to work at 12 and 18 months were identified
      using multivariate logistic regression. RESULTS: More than 80% of patients
      returned to work during the study period, and 87% reported that their employer
      was accommodating to their cancer illness and treatment. After adjusting for
      demographic characteristics, health status, cancer stage, treatment, and job
      type, heavy lifting on the job (odds ratio = 0.42; 95% CI, 0.18 to 0.99),
      perceived employer accommodation for cancer illness and treatment (odds ratio =
      2.2; 95% CI, 1.03 to 4.8), and perceived employer discrimination because of a
      cancer diagnosis (odds ratio = 0.27; 95% CI, 0.10 to 0.71) were independently
      associated with return to work at 12 months after breast cancer diagnosis, and
      perceived employer accommodation (odds ratio = 2.3; 95% CI, 1.06 to 5.1) was
      independently associated with return to work at 18 months after breast cancer
      diagnosis. CONCLUSION: A high percentage of employed breast cancer patients
      returned to work after treatment, and workplace accommodations played an
      important role in their return. In addition, perceived employer discrimination
      because of cancer was negatively associated with return to work for breast cancer
      survivors. Employers seem to have a pivotal role in breast cancer patients'
      successful return to work.

PMID- 16421416
TI  - Assessing BRCA carrier probabilities in extended families.
AB  - PURPOSE: Carrier prediction models estimate the probability that a person has a
      BRCA mutation. We evaluated the accuracy of the BOADICEA model and compared its
      performance with that of other models (BRCAPRO, Myriad I and II, Couch, and
      Manchester Scoring System). We also studied the effect of extended family
      information on risk estimation using BOADICEA. METHODS: We compared the area
      under receiver operating characteristic curves generated from 472 families with
      one member tested for BRCA mutations. We calculated sensitivity, specificity, and
      predictive values at an estimated probability of 10% and explored the biases of
      carrier prediction. RESULTS: BOADICEA performed better than the other models in
      Ashkenazi Jewish (AJ) families, BRCAPRO performed slightly better in non-AJ
      families, and Myriad II performed comparably well in both groups. Including
      extended family information in BOADICEA yielded slightly better performance than
      did limiting the information to second-degree relatives. Using a 10% cutoff
      point, BOADICEA and Myriad II were most sensitive in predicting BRCA1/2 mutations
      in AJ families, and Myriad II was most sensitive in non-AJ families. The
      Manchester Scoring System was the most sensitive and least specific in a subgroup
      of non-AJ families. BOADICEA and BRCAPRO tended to underestimate the observed
      risk at low estimated probabilities and overestimate it at higher probabilities.
      CONCLUSION: The BOADICEA, BRCAPRO, and Myriad II models performed similarly.
      Including second-degree relatives slightly improved carrier prediction by
      BOADICEA. The Myriad II model was the easiest to implement.

PMID- 16421417
TI  - The use of radiation as a component of breast conservation therapy in National
      Comprehensive Cancer Network Centers.
AB  - PURPOSE: Benchmark data regarding quality measures of breast cancer management
      are needed. We investigated rates of radiation use after breast conservation
      therapy (BCT) for patients treated for ductal carcinoma-in-situ (DCIS) or
      invasive breast cancer at National Comprehensive Cancer Network (NCCN) centers.
      PATIENTS AND METHODS: We studied 3,333 consecutive patients treated between 1997
      and 2002 with BCT for DCIS (n = 587) or for stage I or II breast cancer (n =
      2,746) in eight NCCN centers. RESULTS: The overall rate of radiation therapy use
      was 91%, with a lower frequency of radiation use in DCIS versus invasive breast
      cancers (82% v 94%; odds ratio [OR] = 0.31; P < .0001). In a multivariable
      analysis of the patients with DCIS, the only factor significantly associated with
      lower rates of radiation use was low/intermediate grade (OR = 0.19; P = .0003).
      For patients with invasive breast cancer, significant factors were presence of
      comorbidity (OR = 0.53; P = .0005), tubular histology (OR = 0.39; P = .02), type
      of health insurance (P = .0072), and the NCCN institution (P = .0005). The model
      also showed lower rates of radiation use in patients with stage II disease who
      did not receive systemic therapy (OR = 0.01; P = .0001), younger patients who did
      not receive systemic therapy (P = .003); and older patients with stage I disease
      (P < .0001). CONCLUSION: Radiation use as a component of BCT was high for
      patients seen at NCCN centers; however, there was variability in practice
      patterns noted across institutions. Radiation was most commonly omitted in
      patients with favorable disease characteristics, patients with comorbidities, and
      patients who also did not receive guideline-recommended systemic treatment.

PMID- 16421418
TI  - Multicycle dose-intensive chemotherapy for women with high-risk primary breast
      cancer: results of International Breast Cancer Study Group Trial 15-95.
AB  - PURPOSE: To compare adjuvant dose-intensive epirubicin and cyclophosphamide
      chemotherapy administered with filgrastim and progenitor cell support (DI-EC)
      with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with
      early-stage breast cancer and a high risk of relapse, defined as stage II disease
      with 10 or more positive axillary nodes; or an estrogen receptor-negative or
      stage III tumor with five or more positive axillary nodes. PATIENTS AND METHODS:
      Three hundred forty-four patients were randomized after surgery to receive seven
      cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2
      plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6
      weeks. All patients were assigned tamoxifen at the completion of chemotherapy.
      The primary end point was disease-free survival (DFS). RESULTS: After a median
      follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI
      EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for
      SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to
      1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT,
      with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight
      cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who
      received DI-EC. Women with hormone receptor-positive tumors benefited
      significantly from DI-EC. CONCLUSION: There was a trend in favor of DI-EC with
      respect to disease-free survival. A larger trial or meta-analysis will be
      required to reveal the true effect of dose-intensive therapy.

PMID- 16421419
TI  - OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and
      Go fashion in advanced colorectal cancer--a GERCOR study.
AB  - PURPOSE: In metastatic colorectal cancer, a combination of leucovorin (LV) and
      fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen.
      The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped
      in patients who are still responding. This study evaluates a new strategy of
      intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified
      leucovorin and fluorouracil regimen with high-dose oxaliplatin. PATIENTS AND
      METHODS: Previously untreated patients were randomly assigned to either FOLFOX4
      administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles,
      maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm
      B). RESULTS: Six hundred twenty patients were enrolled, including an exploratory
      cohort of 95 elderly or poor prognosis patients. Median progression-free survival
      and survival times were 9.0 and 19.3 months, respectively, in patients allocated
      to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated
      to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2%
      with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4
      toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in
      arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B.
      Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3%
      of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only
      40.1% of the patients but achieved responses or stabilizations in 69.4% of these
      patients. CONCLUSION: Oxaliplatin can be safely stopped after six cycles in a
      FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin
      reintroduction.

PMID- 16421420
TI  - Phase II study of temozolomide and thalidomide in patients with metastatic
      neuroendocrine tumors.
AB  - PURPOSE: Standard, intravenous chemotherapy regimens for neuroendocrine tumors
      have been associated with limited response rates and significant toxicity. We
      evaluated the efficacy of an oral regimen of temozolomide and thalidomide in
      patients with metastatic carcinoid, pheochromocytoma, or pancreatic
      neuroendocrine tumors. PATIENTS AND METHODS: Twenty-nine patients were treated
      with a combination of temozolomide, administered at a dose of 150 mg/m2 for 7
      days, every other week, and thalidomide at doses of 50 to 400 mg daily. Patients
      were followed for evidence of toxicity, biochemical response, radiologic
      response, and survival. RESULTS: Treatment with temozolomide and thalidomide was
      associated with an objective biochemical (chromogranin A) response rate of 40%,
      and a radiologic response rate of 25% (45% among pancreatic endocrine tumors, 33%
      among pheochromocytomas, and 7% among carcinoid tumors). The median duration of
      response was 13.5 months, 1-year survival was 79%, and 2-year survival was 61%.
      The median administered dose of temozolomide was 150 mg/m(2), and the median
      administered dose of thalidomide was 100 mg daily. Grade 3-4 toxicities were
      uncommon, with the exception of grade 3-4 lymphopenia, which developed in 69% of
      the patient population. Opportunistic infections occurred in three patients (10%)
      during the time of lymphopenia, and included single cases of Pneumocystis carinii
      pneumonia, disseminated varicella zoster virus, and herpes simplex virus.
      CONCLUSION: Orally administered temozolomide and thalidomide seems to be an
      active regimen for the treatment of neuroendocrine tumors. In this 29-patient
      study, this regimen appeared more active in pancreatic endocrine tumors than in
      carcinoid tumors.

PMID- 16421421
TI  - Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non
      small-cell lung cancer: meta-analysis of randomized trials.
AB  - PURPOSE: Systemic treatments for advanced non-small-cell lung cancer have low
      efficacy and high toxicity. Some Chinese herbal medicines have been reported to
      increase chemotherapy efficacy and reduce toxicity. In particular, Astragalus has
      been shown to have immunologic benefits by stimulating macrophage and natural
      killer cell activity and inhibiting T-helper cell type 2 cytokines. Many
      published studies have assessed the use of Astragalus and other Chinese herbal
      medicines in combination with chemotherapy. We sought to evaluate evidence from
      randomized trials that Astragalus-based Chinese herbal medicine combined with
      platinum-based chemotherapy (versus platinum-based chemotherapy alone) improves
      survival, increases tumor response, improves performance status, or reduces
      chemotherapy toxicity. METHODS: We searched CBM, MEDLINE, TCMLARS, EMBASE,
      Cochrane Library, and CCRCT databases for studies in any language. We grouped
      studies using the same herbal combinations for random-effects meta-analysis.
      RESULTS: Of 1,305 potentially relevant publications, 34 randomized studies
      representing 2,815 patients met inclusion criteria. Twelve studies (n = 940
      patients) reported reduced risk of death at 12 months (risk ratio [RR] = 0.67;
      95% CI, 0.52 to 0.87). Thirty studies (n = 2,472) reported improved tumor
      response data (RR = 1.34; 95% CI, 1.24 to 1.46). In subgroup analyses, Jin Fu
      Kang in two studies (n = 221 patients) reduced risk of death at 24 months (RR =
      0.58; 95% CI, 0.49 to 0.68) and in three studies (n = 411) increased tumor
      response (RR = 1.76; 95% CI, 1.23 to 2.53). Ai Di injection (four studies; n =
      257) stabilized or improved Karnofsky performance status (RR = 1.28; 95% CI, 1.12
      to 1.46). CONCLUSION: Astragalus-based Chinese herbal medicine may increase
      effectiveness of platinum-based chemotherapy when combined with chemotherapy.
      These results require confirmation with rigorously controlled trials.

PMID- 16421422
TI  - Comparison between patients with Philadelphia-positive chronic phase chronic
      myeloid leukemia who obtained a complete cytogenetic response within 1 year of
      imatinib therapy and those who achieved such a response after 12 months of
      treatment.
AB  - PURPOSE: Imatinib mesylate is a potent inhibitor of BCR-ABL, the constitutively
      active tyrosine kinase protein critical for the pathogenesis of chronic myeloid
      leukemia. PATIENTS AND METHODS: We reviewed 284 patients with late chronic-phase
      Philadelphia chromosome (Ph) -positive chronic myeloid leukemia treated with
      imatinib 400 mg daily after interferon-alpha failure. In a retrospective study,
      we evaluated the pattern and rapidity of the response to imatinib, comparing the
      cytogenetic and molecular responses, progression-free and overall survival rates
      in patients who obtained a complete cytogenetic response within 1 year of
      treatment (early responders), and in patients where a complete cytogenetic
      response was detected after 12 months (late responders). RESULTS: After 3 or 4
      years of treatment, the molecular response of the late cytogenetic responders was
      similar to that of the early cytogenetic responders. At 36 months of treatment
      the amount of residual disease measured by standardized quantitative reverse
      transcriptase polymerase chain reaction was 0.00047 in late responders versus
      0.00022 in early responders, and at 48 months it was 0.00019 versus 0.00026
      (median values, P value = nonsignificant). The estimated 4-year progression-free
      survival rate was 88% for early responders and 100% for late responders, while
      the estimated 4-year overall survival rates were 92% and 100% for early and late
      responders, respectively. CONCLUSION: The sensitivity and the response (cytogenic
      and molecular) to imatinib may require 1 year or more. Long-term follow-up
      results continue to improve in terms of rates and durability of the complete
      cytogenetic response, major or complete molecular response, and progression-free
      and overall survival.

PMID- 16421423
TI  - Long-term risk of cardiovascular disease in 5-year survivors of testicular
      cancer.
AB  - PURPOSE: To evaluate the long-term risk of cardiovascular disease (CVD) in
      survivors of testicular cancer (TC). PATIENTS AND METHODS: We compared CVD
      incidence in 2,512 5-year survivors of TC, who were treated between 1965 and
      1995, with general population rates. Treatment effects on CVD risk were
      quantified in multivariate Cox regression analysis. RESULTS: After a median
      follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute
      myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary
      heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000
      person-years. The SIR for MI was significantly increased in nonseminoma survivors
      with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86)
      but significantly decreased for survivors with attained ages of 55 years or older
      (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7
      fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone,
      whereas infradiaphragmatic irradiation was not associated with an increased MI
      risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was
      associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and
      bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95%
      CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI
      risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with
      a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk. CONCLUSION:
      Nonseminomatous TC survivors experience a moderately increased MI risk at young
      ages. Physicians should be aware of excess CVD risk associated with mediastinal
      radiotherapy, PVB CT, and recent smoking. Intervention in modifiable
      cardiovascular risk factors is especially important in TC survivors. Whether BEP
      treatment increases CVD risk should be evaluated after more prolonged follow-up.

PMID- 16421424
TI  - Risk of selected subsequent carcinomas in survivors of childhood cancer: a report
      from the Childhood Cancer Survivor Study.
AB  - PURPOSE: To determine the risk of subsequent carcinomas other than breast,
      thyroid, and skin, and to identify factors that influence the risk among
      survivors of childhood cancer. PATIENTS AND METHODS: Subsequent malignant
      neoplasm history was determined in 13,136 participants (surviving > or = 5 years
      postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood
      Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using
      Surveillance, Epidemiology, and End Results data. RESULTS: In 71 individuals, 71
      carcinomas were diagnosed at a median age of 27 years and a median elapsed time
      of 15 years in the genitourinary system (35%), head and neck area (32%),
      gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%)
      had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in
      a previous radiotherapy field. Risk was significantly elevated following all
      childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma
      (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had
      a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's
      lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas.
      Significantly elevated risk of head and neck carcinoma occurred in survivors of
      soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR =
      20.9). CONCLUSION: Young survivors of childhood cancers are at increased risk of
      developing subsequent carcinomas typical of later adulthood, underscoring the
      importance of long-term follow-up and risk-based screening. Follow-up of the
      cohort is ongoing to determine lifetime risk and delineate individual
      characteristics that contribute to risk.

PMID- 16421425
TI  - Thromboembolism in hospitalized neutropenic cancer patients.
AB  - PURPOSE: Cancer is associated with thrombosis, but the frequency of
      thromboembolism in hospitalized cancer patients receiving current chemotherapy
      regimens is not known. We investigated venous and arterial thromboembolism and
      associated outcomes in hospitalized cancer patients actively receiving therapy,
      as identified by neutropenia. METHODS: We conducted a retrospective cohort study
      using the discharge database of the University HealthSystem Consortium. This
      included 66,106 adult neutropenic cancer patients with 88,074 hospitalizations
      between 1995 and 2002 at 115 medical centers in the United States. RESULTS:
      Thromboembolism was reported in 5,272 patients (8%), with 5.4% patients
      developing venous thromboembolism and 1.5% developing arterial thromboembolism
      during the first hospitalization. Patients with lymphoma and leukemia accounted
      for one third of venous and nearly one half of arterial events. Clinical
      variables most frequently associated with thromboembolism were age > or = 65
      years; primary site of cancer, including lung, GI, gynecologic, and brain; and
      comorbidities, including infection, pulmonary and renal disease, and obesity. In
      hospital mortality was significantly greater in patients with venous (odds ratio
      [OR] = 2.01; 95% CI, 1.83 to 2.22) or arterial thromboembolism (OR = 5.04; 95%
      CI, 4.38 to 5.79). From 1995 to 2002, there was a 36% increase in venous events
      and a 124% increase in arterial events (P < .0001 for trend). CONCLUSION:
      Thromboembolism is frequent in hospitalized neutropenic cancer patients,
      including in perceived low-risk subgroups such as patients with hematologic
      malignancies and nonmetastatic disease, and seems to be increasing.
      Thromboembolism is associated with increased in-hospital mortality. Increased
      efforts at thromboprophylaxis are warranted.

PMID- 16421426
TI  - Impact of cranial radiotherapy on central nervous system prophylaxis in children
      and adolescents with central nervous system-negative stage III or IV
      lymphoblastic lymphoma.
AB  - PURPOSE: In the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) 95
      trial, we tested, against the historical control of the combined trials NHL-BFM90
      and NHL-BFM86, whether prophylactic cranial radiotherapy (PCRT) can be omitted
      for CNS-negative patients with stage III or IV lymphoblastic lymphoma (LBL) with
      sufficient early response. PATIENTS AND METHODS: Apart from the removal of PCRT
      in NHL-BFM95, the chemotherapy of the three trials was identical except for the
      amount of l-asparaginase and daunorubicin during induction. The therapy in NHL
      BFM95 was accepted to be noninferior when compared with trials NHL-BFM90/86 if
      the lower limit of the one-sided 95% CI for the difference in the 2-year
      probability of event-free-survival (pEFS) between target patients of NHL-BFM95
      and the historical controls of NHL-BFM90/86 did not exceed -14%. The target
      patient group consisted of stage III and IV patients who were CNS negative and
      responded well to induction therapy. RESULTS: The number of target patients was
      156 in NHL-BFM95 (median age, 8.6 years; range, 0.2 to 19.5 years) and 163 in NHL
      BFM90/86 (median age, 8.4 years; range, 0.6 to 16.6 years). For the target group,
      the pEFS rates at 2 and 5 years were 86% +/- 3% and 82% +/- 3%, respectively, in
      NHL-BFM95 (median follow-up time, 5.1 years; range, 2.1 to 9.1 years) compared
      with 91% +/- 2% and 88% +/- 3%, respectively in NHL-BFM90/86 (median follow-up
      time, 10.7 years; range, 5 to 15.4 years). The lower limit of the one-sided 95%
      CI for the difference in pEFS was -11% at 2 years and -13% at 5 years. In NHL
      BFM95, one isolated and two combined CNS relapses occurred compared with one
      combined CNS relapse in NHL-BFM90/86. Five-year disease-free-survival rate was
      88% +/- 3% in NHL-BFM95 compared with 91% +/- 2% in NHL-BFM90/86. CONCLUSION: For
      CNS-negative patients with stage III or IV LBL and sufficient response to
      induction therapy, treatment without PCRT may be noninferior to treatment
      including PCRT.

PMID- 16421427
TI  - Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative
      chemotherapy and autologous stem-cell transplantation in refractory
      neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) and toxicity of iodine-131
      metaiodobenzylguanidine ((131)I-MIBG) with carboplatin, etoposide, melphalan
      (CEM) and autologous stem-cell transplantation (ASCT) in refractory
      neuroblastoma. PATIENTS AND METHODS: Twenty-four children with primary refractory
      neuroblastoma and no prior ASCT were entered; 22 were assessable for toxicity and
      response. (131)I-MIBG was administered on day -21, CEM was administered on days 
      7 to -4, and ASCT was performed on day 0, followed by 13-cis-retinoic acid.
      (131)I-MIBG was escalated in groups of three to six patients, stratified by
      corrected glomerular filtration rate (GFR). RESULTS: The MTD for patients with
      normal GFR (> or = 100 mL/min/1.73 m2) was 131I-MIBG 12 mCi/kg, carboplatin 1,500
      mg/m2, etoposide 1,200 mg/m2, and melphalan 210 mg/m2. In the low-GFR cohort, at
      the initial dose level using 12 mCi/kg of 131I-MIBG and reduced chemotherapy, one
      in six patients had dose limiting toxicity (DLT), including veno-occlusive
      disease (VOD). Three more patients in this group had grade 3 or 4 hepatotoxicity,
      and two had VOD, without meeting DLT criteria. There was only one death as a
      result of toxicity among all 24 patients. All assessable patients engrafted, with
      median time for neutrophils > or = 500/microL of 10 days and median time for
      platelets > or = 20,000/microL of 26 days. Six of 22 assessable patients had
      complete or partial response, and 15 patients had mixed response or stable
      disease. The estimated probability of event-free survival and survival from the
      day of MIBG infusion for all patients at 3 years was 0.31 +/- 0.10 and 0.58 +/-
      0.10, respectively. CONCLUSION: 131I-MIBG with myeloablative chemotherapy is
      feasible and effective for patients with neuroblastoma exhibiting de novo
      resistance to chemotherapy.

PMID- 16421428
TI  - Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor
      tipifarnib in children with refractory solid tumors or neurofibromatosis type I
      and plexiform neurofibromas.
AB  - PURPOSE: This pediatric phase I trial of tipifarnib determined the maximum
      tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of tipifarnib in
      children with refractory solid tumors and neurofibromatosis type 1 (NF1) -related
      plexiform neurofibromas. PATIENTS AND METHODS: Tipifarnib was administered twice
      daily for 21 days, repeated every 28 days starting at 150 mg/m2/dose (n = 4),
      with escalations to 200 (n = 12), 275 (n = 12), and 375 (n = 6) mg/m2/dose. The
      MTD was also evaluated on a chronic continuous dosing schedule (n = 6).
      Pharmacokinetic sampling was performed for 36 hours after the first dose and
      peripheral-blood mononuclear cells (PBMCs) were collected at baseline and steady
      state for determination of farnesyl protein transferase (FTase) activity and HDJ
      2 farnesylation. RESULTS: Twenty-three solid tumor and 17 NF1 patients were
      assessable for toxicity. The MTD was 200 mg/m2/dose, and dose-limiting toxicities
      on cycle 1 were myelosuppression, rash, nausea, vomiting, and diarrhea. The 200
      mg/m2/dose was also tolerable on the continuous dosing schedule. Cumulative
      toxicity was not observed in the 17 NF1 patients who received a median of 10
      cycles (range, 1 to 32 cycles). The plasma pharmacokinetics of tipifarnib were
      highly variable but not age dependent. At steady state on 200 mg/m2/dose, FTase
      activity was 30% compared with baseline, and farnesylation of HDJ-2 was inhibited
      in PBMCs. CONCLUSION: Oral tipifarnib is well tolerated in children receiving the
      drug twice daily for 21 days and a continuous dosing schedule at 200 mg/m2/dose,
      which is equivalent to the MTD in adults. The pharmacokinetic profile of
      tipifarnib in children is similar to that in adults, and at the MTD, FTase is
      inhibited in PBMC in vivo.

PMID- 16421429
TI  - CASE 1. Langerhans cell histiocytosis of the thyroid.

PMID- 16421430
TI  - CASE 2. Acquired hypertrichosis: a rare paraneoplastic syndrome in various
      cancers.

PMID- 16421431
TI  - CASE 4. Fibrocystic breast disease in a 16-year-old female with PTEN hamartoma
      tumor syndrome.

PMID- 16421432
TI  - CASE 3. Benign pleural nodules in a patient with esophageal cancer.

PMID- 16421433
TI  - Overstated conclusions of a pooled analysis of bevacizumab in colon cancer.

PMID- 16421434
TI  - Is AGE accumulation a therapeutic target for diabetic complications?

PMID- 16421435
TI  - Regulatory T cells: back to the future.
AB  - Regulatory T cells seem to represent the resurrection of the old suppressor T
      cells. Although of a different phenotype, regulatory T cells are able to suppress
      many T cell mediated immune responses. While most basic knowledge about these
      cells is derived from animal studies, the recent identification of these cells in
      humans has further attributed to their characterisation by in vitro analysis.
      Results obtained have led to broad speculations about therapeutic potential by
      interference with these regulatory T cells. This review is an introduction to the
      world of regulatory T cells and contains an historical overview with respect to
      the identification and characterisation of these T cells. A distinction is made
      between naturally occurring regulatory T cells (nT(reg)), which require cell-cell
      contact for suppression, and inducible regulatory T cells (iT(reg)), which
      predominantly mediate suppression via cytokine dependent pathways. Although only
      limited studies on regulatory T cells in human disease are available today, the
      possible clinical applications are discussed in light of the other side of the
      coin, i.e. the danger of interfering with homeostatic mechanisms in the immune
      system.

PMID- 16421436
TI  - Time course of specific AGEs during optimised glycaemic control in type 2
      diabetes.
AB  - BACKGROUND: Several advanced glycation endproducts (AGEs) are formed in the
      hyperglycaemic state. Although serum AGEs correlate with average glycaemic
      control in patients with type 2 diabetes and predict the development of
      complications, it is not known how serum AGEs change during optimisation of
      diabetes therapy. METHODS: We evaluated the change in serum levels of total AGE
      and the AGEs CML (Nepsilon-carboxymethyllysine) and MGHI (methylglyoxal-derived
      hydroimidazolone), as well as markers of endothelial function in 28 subjects with
      type 2 diabetes, who were poorly controlled on oral agents,before and after the
      institution of insulin therapy. RESULTS: Mean subject age (+/- SEM) was 58 +/- 2
      years,body mass index 27.7 +/- 0.8 kg/m2, and known duration of diabetes was 8.1
      +/- 0.9 years. With insulin treatment fasting blood glucose levels dropped from
      12.1 +/- 0.9 mmol/l to 6.9 +/- 0.3 and 8.1 +/- 0.4 mmol/l after three and six
      months, respectively (both p<0.001), while HbA1c decreased from 10.0 +/- 0.3 to
      7.8 +/- 0.2% (p<0.001). Endothelial function improved as indicated by a small but
      significant decrease in soluble intercellular cell adhesion molecule (sICAM-1)
      (152 +/- 10 to 143 +/- 8 ng/ml, p<0.02)and sE-selectin (111 +/- 16 to 102 +/-12
      ng/ml, p<0.02)levels. In contrast, we observed only a tendency towards a decrease
      in CML levels (110 +/-22 to 86 +/- 13 microg/mg protein, p=ns), but a small
      increase of MGHI (from 0.23 +/- 0.02 to 0.29 +/- 0.04 U/mg protein, p<0.02). At
      baseline, 16 patients were on metformin, which is known to reduce methylglyoxal
      levels and reduce generation of reactive oxygen species. They had similar levels
      of CML and MGHI to the 12 non-metformin users, although their HbA1c was lower
      (9.4 +/- 0.3 vs 10.7 +/- 0.6 %). During insulin, patients receiving concomitant
      metformin therapy showed a similar course of CML and MGHI to those not taking
      metformin. CONCLUSION: Although insulin therapy improved HbA1c and markers of
      endothelial function, the levels of serum AGEs did not follow the same time
      course. This suggests that these specific AGEs are influenced by other factors in
      addition to overall glycaemia, such as oxidative stress.

PMID- 16421437
TI  - Fascioliasis: a report of five cases presenting with common bile duct
      obstruction.
AB  - Fascioliasis is a zoonotic infection caused by Fasciola hepatica. It is rarely
      seen with icterus caused by obstruction of the common bile duct. We report five
      patients with obstructive jaundice due to Fasciola hepatica, who were diagnosed
      and managed with endoscopic retrograde cholangiopancreatography (ERCP). All cases
      were admitted to hospital with complaints of icterus and pain in the right upper
      quadrant of the abdomen; their biochemical values were interpreted as obstructive
      jaundice. Ultrasound and computer tomography (CT) revealed biliary dilatation in
      the common bile duct, but did not help to clarify the differential diagnosis.
      ERCP showed the presence of Fasciola hepatica in the common bile duct. After
      removing the flukes, the symptoms disappeared and the biochemical values returned
      to normal. Biliary fascioliasis should be considered in the differential
      diagnosis of obstructive jaundice. This report confirms the diagnostic and
      therapeutic role of ERCP in patients with obstructive jaundice caused by biliary
      fascioliasis.

PMID- 16421439
TI  - Cyclical Cushing's syndrome due to an atypical thymic carcinoid.
AB  - A 43-year-old man presented with fluctuating symptoms of weight gain, shortness
      of breath, pretibial oedema, associated with anxiety and memory disturbances.
      Laboratory investigation revealed an adrenocorticotropin (ACTH)-dependent
      cyclical Cushing's syndrome characterised by remarkable variations in urinary
      cortisol excretions ranging from 27 to 28,050 nmol/ 24 h. Magnetic resonance
      imaging (MRI ) of the pituitary was normal and ectopic ACTH production was
      suspected. A tumour in the right anterior mediastinum was revealed on octreotide
      receptor scintigraphy, which had initially been overlooked on computed tomography
      (CT) scanning. A thymic carcinoid tumour was suspected, which was supported by
      increased levels of urinary serotonin, while platelet serotonin and urinary 5
      hydroxyindoleacetic acid levels were normal. The tumour was removed surgically
      and histological examination revealed an atypical thymic carcinoid tumour.
      Postoperatively, the patient's symptoms disappeared rapidly. He underwent
      external radiotherapy and is still free of symptoms after almost two years of
      follow-up. For clinical practice, a cyclical Cushing's syndrome should be
      suspected in any patient with clinical signs of Cushing's syndrome but normal
      biochemistry. Repeated measurement of urinary cortisol excretion is then required
      to establish or rule out the diagnosis.

PMID- 16421438
TI  - Mural aortic thrombus and peripheral embolisation in a patient with
      hyperhomocysteinaemia.
AB  - A mobile thrombus of the descending thoracic aorta in young people is extremely
      uncommon. We describe a 38-year-old woman with a mural thrombus in the proximal
      aorta complicated by peripheral embolisation, due to hyperhomocysteinaemia.

PMID- 16421440
TI  - Photo quiz. Melaena in a liver transplant recipient.

PMID- 16421442
TI  - Is radiation damage dependent on the dose rate used during macromolecular
      crystallography data collection?
AB  - This paper focuses on the radiation-damage effects when applying the same total X
      ray dose to protein crystals at different dose rates. These experiments have been
      performed on both a selenomethionated protein and on bovine trypsin using dose
      rates that span nearly two orders of magnitude. The results show no clear dose
      rate effect on the global indicators of radiation damage, but a small measurable
      dose-rate effect could be found when studying specific radiation damage. It is
      hypothesized that this observed dose-rate effect relates to differences in the
      steady-state free-radical concentration.

PMID- 16421443
TI  - The structure of human deoxycytidine kinase in complex with clofarabine reveals
      key interactions for prodrug activation.
AB  - Clofarabine [2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6
      amine] is a hybrid of the widely used anticancer drugs cladribine and
      fludarabine. It is the precursor of an effective chemotherapeutic agent for
      leukemias and other hematological malignancies and received accelerated approval
      by the FDA for the treatment of pediatric patients with relapsed or refractory
      acute lymphoblastic leukemia. Clofarabine is phosphorylated intracellularly by
      human deoxycytidine kinase (dCK) to the 5'-monophosphate, which is the rate
      limiting step in activation of the prodrug. dCK has a broad substrate
      specificity, with a much higher activity to deoxycytidine than to deoxyadenosine
      and deoxyguanosine. As a purine-nucleoside analog, clofarabine is a better
      substrate of dCK than deoxycytidine. The crystal structure of dCK has been solved
      previously in complex with pyrimidine nucleosides and ADP [Sabini et al. (2003),
      Nature Struct. Biol. 10, 513-519]. In the current study, the crystal structure of
      clofarabine- and ADP-bound dCK was solved to 2.55 angstroms by molecular
      replacement. It appears that the enzyme takes the same conformation as in the
      structures of the pyrimidine nucleoside-bound complexes. The interactions between
      2-Cl and its surrounding hydrophobic residues contribute to the high catalytic
      efficiency of dCK for clofarabine.

PMID- 16421444
TI  - Structure of Toxoplasma gondii adenosine kinase in complex with an ATP analog at
      1.1 angstroms resolution.
AB  - The obligate intracellular parasite Toxoplasma gondii is incapable of
      synthesizing purine nucleotides de novo and relies completely on purines salvaged
      from the host cells. Adenosine is the preferred precursor and is phosphorylated
      by adenosine kinase (AK), the most active enzyme in adenosine metabolism in T.
      gondii. AK thus represents a potential chemotherapeutic target for the treatment
      of T. gondii infections. The previously solved structures of unliganded AK and AK
      in complex with adenosine (or 7-iodotubercidin) and an ATP analog revealed a
      novel catalytic mechanism. A domain closure triggered by a GG switch upon
      adenosine binding sequesters the adenosine and gamma-phosphate of ATP from the
      solvent. The formation of the anion hole induced by the ATP binding completes the
      structural requirements for catalysis. In the current study, the structure of a
      binary complex of AK and the non-hydrolysable ATP analog AMP-PCP was determined
      to 1.1 angstroms resolution. The overall structure is similar to the apoenzyme,
      with an open conformation. AMP-PCP is bound in two relaxed conformations and
      without anchoring by Arg136. The induced anion hole is the same as that in the
      ternary complex AK-adenosine-AMP-PCP. This structure provides direct evidence
      that ATP binding at millimolar concentrations does not require adenosine binding
      as a prerequisite.

PMID- 16421445
TI  - Fluorescence detection of nucleic acids and proteins in multi-component crystals.
AB  - A highly sensitive and specific assay for the rapid detection of nucleic acids in
      crystals of macromolecular complexes is reported. The assay is based on the
      observation of crystals under a fluorescence microscope after incubation with a
      fluorescent dye that specifically binds nucleic acids. The assay allows clear
      distinction between crystals of free RNA polymerase II and crystals of the
      polymerase bound to DNA and RNA or RNA alone, even when the nucleic acids account
      for only 3% of the crystalline material. Fluorescence detection was also used to
      monitor the diffusion and accumulation of a fluorescence-labelled polymerase
      binding protein in preformed polymerase crystals. Additional experiments suggest
      the general applicability of these fluorescence assays for the characterization
      of crystal contents.

PMID- 16421446
TI  - 2.0 angstroms structure of prostaglandin H2 synthase-1 reconstituted with a
      manganese porphyrin cofactor.
AB  - Prostaglandin H2 synthase (EC 1.14.99.1) is a clinically important drug target
      that catalyzes two key steps in the biosynthesis of the eicosanoid hormones. The
      enzyme contains spatially distinct cyclooxygenase and peroxidase active sites,
      both of which require a heme cofactor. Substitution of ferric heme by Mn(III)
      protoporphyrin IX greatly diminishes the peroxidase activity, but has little
      effect on the cyclooxygenase activity. Here, the 2.0 angstroms resolution crystal
      structure of the Mn(III) form of ovine prostaglandin H2 synthase-1 is described
      (R = 21.8%, R(free) = 23.7%). Substitution of Mn(III) for Fe(III) causes no
      structural perturbations in the protein. However, the out-of-plane displacement
      of the manganese ion with respect to the porphyrin is greater than that of the
      iron by approximately 0.2 angstroms. This perturbation may help to explain the
      altered catalytic properties of the manganese enzyme.

PMID- 16421447
TI  - Structure of DraD invasin from uropathogenic Escherichia coli: a dimer with
      swapped beta-tails.
AB  - The dra gene cluster of uropathogenic strains of Escherichia coli produces
      proteins involved in bacterial attachment to and invasion of the eukaryotic host
      tissues. The crystal structure of a construct of E. coli DraD possessing an
      additional C-terminal extension of 13 amino acids, including a His6 tag, has been
      solved at a resolution of 1.05 angstroms. The protein forms symmetric dimers
      through the exchange of the C-terminal beta-strands, which participate in the
      immunoglobulin-like beta-sandwich fold of each subunit. This structure confirms
      that DraD is able to act as an acceptor in the donor-strand complementation
      mechanism of fiber formation but, in contrast to DraE adhesin, its native
      sequence does not have a donor strand; therefore, DraD can only be located at the
      tip of the fiber.

PMID- 16421448
TI  - Extension to 2268 atoms of direct methods in the ab initio determination of the
      unknown structure of bacteriophage P22 lysozyme.
AB  - The X-ray crystal structure of the previously unknown bacteriophage P22 lysozyme,
      the product of gene 19, has been determined ab initio by direct methods using the
      program SIR2002. The presence of several partially occupied iodine anions and
      samarium cations augmented the ability of direct methods to locate all 2268 non-H
      protein atoms in the asymmetric unit, making this one of the largest structures
      to date to be determined ab initio. The iodides were introduced from a quick
      soak, which the crystal survived sufficiently well to diffract to 1.04 angstroms
      resolution. The complete heavy-atom substructure contributed 6.6% of the total
      scattering power. The initial determination of the structure assumed that there
      were two iodide ions in the asymmetric unit, although it was later determined
      that these sites correspond to partially occupied samarium ions. Tests suggested
      that it is better to overestimate rather than underestimate the heavy-atom
      content. While experimental phases from all of the successful tests were of high
      quality, the best results came from a SAD experiment using the programs SHELXD
      and SHELXE. Nonetheless, ab initio structure determination by direct methods was
      found to be a viable alternative to traditional protein crystallographic methods
      provided that the X-ray data extend to atomic resolution and heavy atoms with
      sufficient scattering power are present in the crystal.

PMID- 16421449
TI  - Structures of the Dsk2 UBL and UBA domains and their complex.
AB  - The yeast proteins Dsk2 and Rad23 belong to a family of proteins that contain an
      N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated
      domain (UBA). Both Dsk2 and Rad23 function as adaptors to target ubiquitin
      labelled proteins to the proteasome through recognition of polyubiquitin (four or
      more K48-linked ubiquitins) by their UBA domains and to the yeast proteasomal
      subunit Rpn1 by their UBL domains. The crystal structures of the Dsk2 UBL domain,
      the Dsk2 UBA domain and the Dsk2 UBA-UBL complex are reported. In the crystal,
      the Dsk2 UBA domains associate through electrostatic interactions to form
      ninefold helical ribbons that leave the ubiquitin-binding surface exposed. The
      UBA-UBL complex explains the reduced affinity of the UBA domain for UBL compared
      with ubiquitin and has implications for the regulation of Dsk2 adaptor function
      during ubiquitin-mediated proteasomal targeting. A model is discussed in which
      two or more Dsk2 UBA molecules may selectively bind to K48-linked polyubiquitin.

PMID- 16421450
TI  - LAFIRE: software for automating the refinement process of protein-structure
      analysis.
AB  - Manual intervention is usually required in the multiple rounds of refinement of
      protein crystal structures, including linking and/or extending the fragments of
      the initial model and rebuilding (fitting) ill-matched residues using computer
      graphics software. Such manual modification is both time-consuming and requires a
      great deal of expertise in crystallography. Consequently, the refinement process
      becomes the bottleneck for high-throughput structure analysis. A program, Local
      correlation coefficient-based Automatic FItting for REfinement (LAFIRE), has been
      developed to achieve manual intervention-free refinement. This program was
      designed to perform the entire process of protein structural refinement
      automatically using the refinement programs CNS1.1 (CNS v.1.1) or REFMAC5. The
      automatic process begins from an initial model, which can be approximate,
      fragmentary or even only main-chain, and refines it to the final model including
      water molecules, controlled by monitoring the R(free) factor. More than 30
      structures have now been refined successfully in a fully or semi-automatic manner
      within a few hours or days using LAFIRE.

PMID- 16421451
TI  - New crystal structures of human glutathione transferase A1-1 shed light on
      glutathione binding and the conformation of the C-terminal helix.
AB  - Human glutathione transferase A1-1 is a well studied enzyme, but despite a wealth
      of structural and biochemical data a number of aspects of its catalytic function
      are still poorly understood. Here, five new crystal structures of this enzyme are
      described that provide several insights. Firstly, the structure of a complex of
      the wild-type human enzyme with glutathione was determined for the first time at
      2.0 angstroms resolution. This reveals that glutathione binds in the G site in a
      very similar fashion as the glutathione portion of substrate analogues in other
      structures and also that glutathione binding alone is sufficient to stabilize the
      C-terminal helix of the protein. Secondly, we have studied the complex with a
      decarboxylated glutathione conjugate that is known to dramatically decrease the
      activity of the enzyme. The T68E mutant of human glutathione transferase A1-1
      recovers some of the activity that is lost with the decarboxylated glutathione,
      but our structures of this mutant show that none of the earlier explanations of
      this phenomenon are likely to be correct. Thirdly, and serendipitously, the apo
      structures also reveal the conformation of the crucial C-terminal region that is
      disordered in all previous apo structures. The C-terminal region can adopt an
      ordered helix-like structure even in the apo state, but shows a strong tendency
      to unwind. Different conformations of the C-terminal regions were observed in the
      apo states of the two monomers, which suggests that cooperativity could play a
      role in the activity of the enzyme.

PMID- 16421453
TI  - High-resolution structure of recombinant Trichomonas vaginalis thioredoxin.
AB  - The structure of thioredoxin from the anaerobic organism Trichomonas vaginalis
      (TvTrx) has been determined at 1.9 angstroms resolution. The structure is that of
      a typical thioredoxin: a five-stranded beta-sheet structure with two alpha
      helices on either side. The active site of the protein carries a Trp-Cys-Gly-Pro
      Cys motif, residues 34-38, at the N-terminus of an alpha-helix (alpha2). The
      cysteine residues in this motif form a redox-active disulfide necessary for
      thioredoxin activity. With high-resolution data available, it was possible to
      model numerous amino-acid side chains in alternate conformations and this
      includes the redox-active disulfide cysteine residues. The sample was initially
      in the oxidized state and the use of X-rays from an intense third-generation
      synchrotron source resulted in partial photoreduction of this labile redox
      centre. Comparisons with previously determined thioredoxin structures indicate
      that TvTrx is most similar to the human homologue, although the insertion of
      three residues between strands beta4 and beta5 makes the corresponding turn
      longer and more flexible in TvTrx. In addition, three significant amino-acid
      differences are identified on the protein surfaces near to the active-site Cys35.
      These residues may contribute to the interactions that specific thioredoxins form
      with their cognate physiological partners.

PMID- 16421452
TI  - Molecular replacement with pseudosymmetry and model dissimilarity: a case study.
AB  - Crystals of human T-cell leukemia virus protease (HTLV-1 PR) have been very
      difficult to prepare and only native data extending to 2.6 angstroms resolution
      could be collected. Initial attempts to solve the structure with a variety of low
      sequence-identity models utilizing proteases from other retroviruses and using a
      number of molecular-replacement programs were unsuccessful. The structure was
      finally solved using Phaser, revealing extensive pseudosymmetry and significant
      deviations from the starting models, features that were likely to be responsible
      for the initial failures. The steps taken to solve this structure and some of its
      intriguing crystallographic aspects are discussed.

PMID- 16421455
TI  - N-/R-cadherin expression in dorsal root ganglia and spinal cord.
AB  - Localizations of N- and R-cadherins in dorsal root ganglia and lumbar spinal cord
      of the chick were immunocytochemically examined. As a result, N- and R-cadherin
      appeared to be co-localized on plasmalemma of neurons in dorsal root ganglia that
      were in contact with satellite cells, whereas there was no expression in neurons
      of the ventral horn. These findings indicate the possibility that expression
      pattern of cadherins in the peripheral neuron differs with its functional
      property (e.g. sensory or motor).

PMID- 16421456
TI  - ACE gene polymorphism in children with nephrotic syndrome in the Indonesian
      population.
AB  - BACKGROUND: The angiotensin converting enzyme (ACE) gene carries insertion (I)
      and deletion (D) polymorphism within its intron 16. The presence of D-allele in
      the ACE gene has been reported as a probable genetic risk factor for idiopathic
      nephrotic syndrome (INS), especially the subtype of focal segmental
      glomerulosclerosis (FSGS). The D-allele may be related to poor responsiveness to
      steroid therapy. To clarify the relationship between the D-allele and INS, we
      studied the prevalence of the D-allele in the Javanese-Indonesian patients.
      Additionally, we also analyzed relationship between each genotype and steroid
      sensitivity among the MCNS patients. METHODS: Eighty-five Javanese-Indonesian
      patients under 15 years of age with INS were enrolled in this study: 16 patients
      with FSGS and 69 patients with minimal change nephrotic syndrome (MCNS). As
      controls, 68 healthy adult Javanese-Indonesians with no history of kidney disease
      volunteered to participate in this study. Genotypes based on the polymorphisms
      (I/D) were determined by using a PCR method. As for the steroid responsiveness,
      the information of 14 out of 16 FSGS patient (87.5%) and 69 out of 69 MCNS
      patients (100%) was available. RESULTS: The genotype frequencies in the FSGS
      patients were II 37% (6/16), ID 44% (7/16) and DD 19% (3/16), and the D-allele
      frequency was 41% (13/32). The genotype frequencies in the MCNS patients were II
      56% (39/69), ID 38% (26/69) and DD 6% (4/69), and the D-allele frequency was 25%
      (34/138). The genotype frequencies in the controls were II 60% (41/68), ID 31%
      (21/68), and DD 9% (6/68), and the D-allele frequency was 26% (33/136). None of
      the FSGS patients were sensitive to steroid, while almost all MCNS patients
      (66/69) were sensitive to steroid. The genotype frequencies among steroid
      sensitive MCNS patients were consistent with those of the controls, suggesting
      that there was no relationship between each genotype and steroid sensitivity.
      CONCLUSIONS: In the Javanese-Indonesian population, none of the comparisons
      showed any significant differences in the genotypic distribution and allelic
      frequencies among the three groups, FSGS, MCNS and controls, although D-allele
      tended to exist more frequently in FSGS patients than in the MCNS patients and
      controls. In addition, the D-allele frequency was not related to steroid
      sensitivity in the MCNS patients.

PMID- 16421457
TI  - Determinants of first- and second-generation antipsychotic drug use in clinically
      unstable patients with schizophrenia treated in four European countries.
AB  - The present study investigated the use of antipsychotics in a sample of
      clinically unstable patients with schizophrenia who were recruited in four
      European sites. The study aimed: (i) to test whether the length of previous
      antipsychotic exposure was associated with the choice of antipsychotic
      medication; (ii) to test whether the severity of illness was associated with the
      use of second-generation antipsychotic agents (SGAs) or with the concomitant use
      of both first-generation antipsychotics (FGAs) and SGAs; and (iii) to investigate
      differences between study sites. Participants were recruited from patients under
      the care of psychiatric services serving geographical catchment areas in Croydon
      (UK), Verona (Italy), Amsterdam (The Netherlands) and Leipzig (Germany).
      Clinically unstable patients with a clinical diagnosis of schizophrenia and a
      research diagnosis of schizophrenia, established using the Item Group Checklist
      of the Schedule for Clinical Assessment in Neuropsychiatry, were enrolled.
      Sociodemographic and clinical data, including current antipsychotic drug therapy,
      psychopathology, adherence, insight, side-effects, attitudes towards medication
      and quality of life, were gathered. Three hundred and ninety patients were
      analysed in total. Almost 60% received SGAs, less than one-third FGAs, and less
      than 15% received both drug classes. Those receiving SGAs were younger and with a
      shorter length of antipsychotic drug therapy, whereas those receiving both drug
      classes were more often separated or widowed, unemployed and with a long history
      of antipsychotic drug therapy. The distribution of patients receiving FGAs, SGAs
      and both drug classes by illness-related variables showed that patients receiving
      both drug classes were more severely ill and complained of more side-effects.
      Using patients receiving FGAs as the reference category, multinomial logistic
      regression analysis showed that the length of antipsychotic treatment was
      negatively correlated with receiving SGAs, and that the severity of illness and
      being separated/widowed were positively correlated with receiving both drug
      classes. Compared with patients in Leipzig, patients in Amsterdam, Croydon and
      Verona were less frequently treated with SGAs and with combinations of both drug
      classes. Consistent with current clinical uncertainty with respect to what
      pharmacological treatment should be provided, patients with a long history of
      antipsychotic exposure were receiving FGAs, SGAs and combinations of both drug
      classes. Physicians tended to reserve polypharmacy for difficult-to-treat
      patients (i.e. for managing situations where, despite the lack of an evidence
      base, there is a pressing need to provide clinical answers).

PMID- 16421458
TI  - Influence of age, gender, body weight and valproate comedication on quetiapine
      plasma concentrations.
AB  - Quetiapine is a second-generation antipsychotic with a favourable risk/benefit
      profile that is increasingly used in psychiatric patients. Similar to other
      antipsychotics, the efficacy and adverse effects of quetiapine depend much more
      on the actual plasma concentration of the active drug than on the prescribed
      dose. The present study investigated whether age, gender, body weight or certain
      comedications influence quetiapine plasma concentration by determining quetiapine
      plasma levels by tandem mass spectrometry in 94 (36 male and 58 female) patients
      aged 42.2 +/- 20.0 years. Older age was a significant predictor of a higher
      quetiapine plasma concentration, with a mean increase of weight-corrected
      concentration/dose ratio of 11% per 10 years of age (P = 0.003). In females, the
      concentration/dose (C/D) ratio was 35.4% higher than in males (adjusted mean
      0.144 ng/ml/mg for males versus 0.195 ng/ml/mg for females, respectively; P =
      0.035). However, after correction for weight, the gender difference in C/D ratio
      dropped to 22% and significance was lost (P = 0.133). Valproate comedication was
      associated with a 77% increase in quetiapine plasma levels (P = 0.016). In
      conclusion, older age, body weight and comedication with valproate have to be
      considered when prescribing quetiapine. Higher plasma levels in female patients
      need to be replicated in larger samples.

PMID- 16421459
TI  - A comparative study of sertraline dosages, plasma concentrations, efficacy and
      adverse reactions in Chinese versus Caucasian patients.
AB  - This prospective 6-week study examined the differences in dosage and steady state
      plasma concentrations of sertraline in Chinese versus Caucasian depressed
      patients. Two groups of Chinese patients from different geographical sites and a
      group of Caucasian patients were evaluated with clinical measures during an
      initial dose of 50 mg/day, with subsequent doses adjusted clinically. The results
      of 17 Australian Chinese (ACHI), 13 Malaysian Chinese (MCHI) and 15 Australian
      Caucasians (AC) were analysed. Despite controlling for weight, the AC subjects
      received a significantly higher dose than both the ACHI (P = 0.002) and the MCHI
      groups (P = 0.012). However, the mean sertraline concentration to dose ratios at
      weeks 1 and 6 were not significantly different between the three groups.
      Sertraline was effective and well tolerated in both ethnic groups with few
      adverse events. Although there was a lack of difference between groups in the
      pharmacokinetic results, Chinese depressed patients appeared to require lower
      dosages with consequently lower plasma concentrations of sertraline compared to
      Caucasian patients to achieve clinical efficacy. Further studies of the dosages,
      kinetics and adverse effects of selective serotonin reuptake inhibitors linked
      with genotyping are necessary.

PMID- 16421460
TI  - High prevalence of the metabolic syndrome among a Swedish cohort of patients with
      schizophrenia.
AB  - Several cardiovascular risk factors have been linked to antipsychotic treatment
      and cardiovascular mortality is increased in these patients compared to the
      general population. The full metabolic syndrome (or its components) is associated
      with an increased risk of cardiovascular disorders. The prevalence of the
      metabolic syndrome was investigated using a cross-sectional study design in a
      cohort of 269 patients, aged 20-69 years, with schizophrenia living in Northern
      Sweden, and was defined according to the criteria of the National Cholesterol
      Education program. The prevalence of the metabolic syndrome was 34.6% (95% CI =
      28.8-40.3) and highest (43%; 95% CI = 32-53) for participants aged 40-49 years.
      Clozapine treated subjects reached the highest prevalence of the metabolic
      syndrome (48%; 95% CI = 34-62). The prevalence was similar for men (32.8%; 95% CI
      = 25.8-39.8) and women (38.0%; 95% CI = 27.9-48.2). Men had a high prevalence of
      hypertension (49.2%; 95% CI = 41.7-56.6) and women had high prevalence of low
      high-density lipoprotein cholesterol (40.2%; 95% CI = 30.0-50.4) and abdominal
      obesity (75.0%; 95% CI = 66.0-84.0). Subjects with the metabolic syndrome had
      significantly higher mean body mass index (BMI) (P < 0.001), HbA1c (P = 0.002),
      and fasting serum insulin (P < 0.001) compared to non-metabolic syndrome subject.
      Subjects with the metabolic syndrome had also significantly more often a positive
      history of cardiovascular diseases compared to non-metabolic syndrome subjects
      (25.8% versus 12.5%; P = 0.01). Of all study subjects 36.8% were obese (BMI >
      30). These results clearly show that the metabolic syndrome and its components
      are highly prevalent in patients with schizophrenia. Physicians treating patients
      with schizophrenia are recommended to monitor the components included in the
      metabolic syndrome.

PMID- 16421461
TI  - Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia
      patients: a randomized, double-blind, placebo-controlled cross-over study.
AB  - The beneficial effect of sulpiride augmentation of clozapine therapy for
      treatment-resistant schizophrenia patients is enhanced by its antisalivatory
      effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to
      sulpiride, is a substitute benzamide derivative with higher selective binding to
      the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also
      be beneficial in controlling CIH. In a randomized, double-blind, placebo
      controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria)
      inpatients with CIH were randomly initially assigned to add-on amisulpride (nine
      patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11
      patients). Primary outcome was change in the five-point Nocturnal Hypersalivation
      Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome
      Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale
      (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25)
      than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride
      treatment, there was a significant improvement on the negative symptoms subscale
      of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other
      subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a
      strong ameliorating effect on CIH. A long-term, large-scale study with a broader
      dose range is warranted to evaluate the stability of this effect across time.

PMID- 16421462
TI  - Onset of action of escitalopram compared with other antidepressants: results of a
      pooled analysis.
AB  - In general, antidepressant drugs are regarded as too slow acting. Most patients
      who benefit from treatment require more than 2 weeks of therapy to respond to
      treatment. An efficacious and well-tolerated antidepressant drug with an earlier
      onset of effect would be of greater interest to clinicians and patients. To study
      the onset of effect of escitalopram, a selective serotonin reuptake inhibitor
      (SSRI), data were pooled from controlled randomized clinical double-blind trials
      comparing this drug with other antidepressant drugs (SSRIs and venlafaxine XR) in
      major depressive disorder (MDD), with assessments of the primary efficacy
      parameter [mean change in the Montgomery-Asberg Depression Rating Scale (MADRS)
      total score from baseline, using last observation carried forward]. The mean
      change in MADRS total scores was significantly higher for escitalopram-treated
      patients than for patients treated with the comparators on day 7 (-3.9 versus 
      3.4, respectively, P = 0.029). This difference remained significant and in favour
      of escitalopram at all subsequent assessments. Using secondary outcomes (Clinical
      Global Impression of Improvement and Severity scales and early improvement), the
      results consistently showed a statistically significantly faster onset of effect
      of escitalopram compared to other antidepressants. In conclusion, by using the
      MADRS scale and pooling data from the escitalopram clinical trials in MDD
      comparing escitalopram with other active antidepressant drugs, escitalopram was
      shown to be a fast-acting antidepressant with a more rapid onset of effect than
      the comparators, particularly other SSRIs.

PMID- 16421463
TI  - Suicide trends in discharged patients with mood disorders: associations with
      selective serotonin uptake inhibitors and comorbid substance misuse.
AB  - We determined the rates of suicide in two consecutive time intervals of low and
      high selective serotonin reuptake inhibitor (SSRI) prescribing for men and women
      with mood disorders, who were at relatively high risk of suicide, in a discharged
      hospitalized sample. High quality Swedish national registers were cross-linked to
      estimate rates of suicide. The results were stratified by three age-bands, and
      rates of comorbid substance misuse were explored. These were compared with
      general population suicide rates. There were 1606 suicides in discharged patients
      with mood disorders. Suicide rates decreased for all women during 1989-94 and
      1995-2000 [odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.85] and
      a trend was found towards lower rates in men (OR = 0.89, 95% CI = 0.78-1.02).
      Approximately 90% of suicides occurred in those aged over 40 years; thus, the
      inpatient sample lacked the power to discriminate clear effects in the younger
      age groups. There was no increase or decrease in the rates of substance use
      disorders in patients who committed suicide. There were 20 851 suicides in the
      general population during 1989-2000. Suicide rates were lower at all ages for men
      and women in the general population in the interval of high SSRI prescribing. We
      conclude that there is no evidence from this study of an increase in suicide
      rates following the introduction of SSRIs in the general population or in a high
      risk inpatient sample.

PMID- 16421464
TI  - Response, remission and relapse in relation to adherence in primary care
      treatment of depression: a 2-year outcome study.
AB  - Non-adherence to antidepressant drug treatment is common. In a recent study in
      depressed primary care patients, we reported a strong relationship between
      adherence and response after 6 months. With the use of a naturalistic design, the
      patients in that study were prospectively followed for 2 years. The purpose of
      the present study was to investigate the patients' long-term outcome and, in
      particular, to examine the impact of patients' treatment adherence on response,
      remission and relapse. Of the 1031 patients in the intent-to-treat (ITT) sample,
      835 completed the study. After 2 years, the overall remission rate defined as a
      Montgomery-Asberg Depression Rating Scale score of nine or less was 68% in the
      ITT sample analysed with the last observation carried forward (LOCF) technique,
      and 75% in observed cases. In total, 34% of the responders experienced at least
      one relapse. Response rates (LOCF) were significantly higher in adherent compared
      to non-adherent patients at week 24 [95% confidence interval (CI) = 21.4-32.1],
      year 1 (95% CI = 12.3-22.2) and year 2 (95% CI = 9.2-19.0). Remission rates
      (LOCF) were also significantly higher in the group of adherent patients at week
      24 (95% CI = 9.6-21.5), year 1 (95% CI = 10.0-21.5) and year 2 (95% CI = 11.0
      22.0). No relationship between adherence and relapse rate was observed, although
      the mean time from response to first sign of relapse was significantly longer in
      the adherent patients (95% C I= 9-97 days). In conclusion, this 2-year follow-up
      study showed superior long-term recovery in patients who were adherent to
      antidepressant medication compared to non-adherent patients.

PMID- 16421465
TI  - Aripiprazole and suicidality.
AB  - Cases of psychotic symptoms that worsen after treatment with aripiprazole have
      been described. We report the case of a 19-year-old patient who, although her
      psychotic symptoms did not worsen, attempted suicide after switching from
      risperidone to aripiprazole. The patient had not shown any aggressive behaviour
      towards herself or others in the 18 months before the introduction of
      aripiprazole, nor following its discontinuation (12 months). The observed time
      sequence, with the repetition 4 weeks later of high suicidal behaviour, led us to
      consider that this effect might possibly be linked to the aripiprazole treatment,
      which could have increased the risk of suicide in this patient.

PMID- 16421466
TI  - Aripiprazole-induced parkinsonism.
AB  - Dopamine receptor antagonism is associated not only with antipsychotic action,
      but also with the generation of extrapyramidal side-effects of antipsychotic
      medications. Positron emission tomography studies reveal that an approximate 60
      70% blockade of the D2 receptors is required for typical antipsychotics to be
      efficacious, but a blockade of > or =75-80% results in acute extrapyramidal side
      effects. The newer atypical antipsychotics have a lower propensity to produce
      extrapyramidal side-effects. A new class of antipsychotics with a novel
      pharmacological profile and improved tolerability have emerged, comprising the
      'dopamine-serotonin system stabilizers' of which aripiprazole is the first agent.
      We present the case of a patient who developed parkinsonism during treatment with
      aripiprazole.

PMID- 16421467
TI  - Transplant tolerance: converging on a moving target.
AB  - Enthusiasm for tolerance induction has been tempered by the realization that it
      is more difficult to achieve clinically than was predicted by experimental
      models. Unlike the view that the immune response to an allograft is ordered and
      thus predictable, we view alloimmunity as highly plastic and molded by previous
      and ongoing experiences with allogeneic and environmental antigens. This implies
      that an individual's response to an allograft changes over time and that
      responses of seemingly similar individuals may vary greatly. This variability
      highlights the need to develop assays for monitoring the recipient immune
      response as well as individualized methods for therapeutic immune modulation.

PMID- 16421469
TI  - Current results of an organ procurement organization effort to increase
      utilization of donors after cardiac death.

PMID- 16421468
TI  - Impact of donor age and year of transplantation on graft and patient survival
      following liver transplantation for hepatitis C virus.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection has become the most common
      indication for liver transplantation (LT). Graft and patient survival are
      adversely affected by recurrent infection of the graft. Recent publications have
      described an inferior outcome for recently transplanted HCV patients and have
      highlighted the impact of advancing donor age on severity of recurrent HCV. The
      donor age at which a measurable impact on graft and patient outcome can be
      observed has not clearly been defined. In addition, the impact of donor age on
      graft and patient survival for non-HCV patients needs to be examined. METHODS: We
      have examined a large European liver transplant database to define the impact of
      transplantation date and donor age on graft and patient survival for HCV patients
      (n = 4,736) and the impact for a comparison group of transplanted alcoholic liver
      disease patients (ALD, n = 5,406). RESULTS: For the entire cohorts, graft and
      patient survival of HCV patients was inferior to ALD patients. Since 1987, there
      has been a steady and ongoing improvement in the outcome of transplanted ALD
      patients, an improvement not observed for HCV patients. Every year since 1989,
      there has been an increase in liver donor age. Graft and patient survival for
      both ALD and HCV cohorts was adversely affected by advancing donor age.
      Comparison of graft and patient survival for HCV and ALD cohorts was made
      according to donor age (donor age subgrouped <20, 20-30, 30-40, 40-50, 50-60 and
      >60 years of age). For donors younger than 40 years of age, HCV and ALD recipient
      graft and patient survival are not significantly different. For donors older than
      40, HCV recipient graft survival is inferior to ALD graft survival, an
      inferiority that increases for each advancing decade of donor age. For donors
      older than 50 years, HCV recipient patient survival is inferior to ALD patient
      survival, an inferiority that increases when the donor age is greater than 60
      years. CONCLUSION: The results of liver transplantation for European HCV patients
      is inferior to a comparison group of ALD patients, and have not improved during
      the past 15 years. Liver donor age has increased significantly during that
      period. Advancing donor age has an adverse influence on graft and patient
      survival for ALD and HCV patients, but a significantly greater impact is observed
      for HCV patients when the donor is older than 40 years.

PMID- 16421470
TI  - Transmission of infection from live donor to recipient.

PMID- 16421471
TI  - Campath-1H induction and the incidence of infectious complications in adult renal
      transplantation.
AB  - BACKGROUND: The purpose of this study was to evaluate adult renal transplantation
      patients who received a alemtuzumab (Campath-1H)-based induction protocol for the
      incidence of infectious complications. METHODS: We began using 30 mg Campath-1H
      intravenously for induction therapy in May 2003. The patients were treated with a
      maintenance regimen of tacrolimus or mycophenolate mofetil (MMF), and rapidly
      tapered prednisone; valganciclovir was used for CMV prophylaxis. Forty-nine adult
      patients who received renal transplants between May 1, 2003 and June 7, 2004 were
      included. The mean follow-up time was 13.7 months with a range of 10-24 months.
      Data were collected via a retrospective chart review. RESULTS: The infectious
      complications noted in the Campath-1H group were compared with a historical group
      of 56 patients receiving conventional immunosuppression. There was one case of
      cytomegalovirus (CMV) viremia and two cases of CMV disease (one pneumonitis and
      one enteritis). There were four cases of urinary tract infection and one
      extremity cellulitis. One patient developed Cryptococcal meningitis. Eight of the
      49 (16%) patients in the Campath group had an infectious complication, compared
      to 18 out of 56 (32%) in the historical group. CONCLUSION: Campath-1H induction
      for renal transplantation appears to have a low incidence of associated
      infectious complications when compared to historical regimens.

PMID- 16421472
TI  - Use of short tandem repeats for DNA fingerprinting to rapidly diagnose graft
      versus-host disease in solid organ transplant patients.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) is a rare complication following
      liver transplantation and carries a poor prognosis with mortality approaching 90
      95%. Diagnosis of GVHD is often delayed due to early symptoms mimicking more
      common, entities such as drug reactions and viral syndromes. To date, definitive
      diagnosis has been difficult and has relied on a constellation of clinical and
      histopathologic variables. We present the use of short tandem repeat DNA
      "fingerprinting" technology as a method of early, definitive diagnosis of GVHD in
      patients after liver transplantation. METHODS: A patient status-postorthotopic
      cadaveric-liver transplant, with an uncomplicated immediate posttransplant
      course, presented 4 weeks after transplant with fever, diarrhea, and
      maculopapular rash on her palms, soles, and back. The patient's condition
      worsened despite empiric treatment for an infectious etiology. Skin and rectal
      biopsies were suspicious for GVHD. RESULTS: DNA was isolated from the skin and
      rectal biopsies as well as from a donor lymph node. PCR amplification was done
      for nine highly polymorphic short tandem repeats for each specimen and a unique
      DNA "fingerprint" was obtained from each. DNA from skin and rectum demonstrated
      mixed chimerism with both donor and recipient alleles detected. Thorough analysis
      confirmed GVHD. CONCLUSION: Short tandem repeats for DNA fingerprinting
      represents an efficient and reproducible method for the definitive diagnosis of
      GVHD after liver transplantation. Rapid detection of GVHD using this technology,
      coupled with early initiation of therapy, may lead to improved survival for
      patients with GVHD after solid organ transplant.

PMID- 16421474
TI  - Streptozotocin-induced diabetes in large animals (pigs/primates): role of GLUT2
      transporter and beta-cell plasticity.
AB  - BACKGROUND: To induce irreversible diabetes in large animals, the efficiency of
      streptozotocin (STZ) was evaluated in pigs, primates and compared to the gold
      standard model in rats. METHODS: Low (50 mg/kg) and high (150 mg/kg) doses of STZ
      were tested. Hepatic/renal function, glucose metabolism (intravenous glucose
      tolerance tests, fasting blood glucose) and histomorphometry were evaluated prior
      to, 1, and 4 weeks after STZ treatment. RESULTS: In rats and primates, expressing
      a high level of GLUT2 expression on beta cells, a dose of 50 mg/kg STZ induced
      irreversible diabetes (due to the 97% destruction of beta cell mass) without
      provoking liver or renal failure. In pigs, despite the use of high STZ dose,
      partial correction of hyperglycaemia was observed four weeks after STZ injection
      (decreased fasting blood glucose and intravenous glucose tolerance tests;
      increased insulin production). The correction of hyperglycaemia was associated
      with significant hypertrophy of immature pig beta-cell clusters (+30%, P<0.05),
      whereas no hypertrophy was observed in rats/primates. CONCLUSION: These results
      demonstrated that STZ might be used to induce irreversible diabetes in rats and
      primates. In contrast, the low STZ sensitivity in pigs related to a low
      expression of GLUT2, higher number of immature beta cells and compensatory beta
      cell hypertrophy, renders STZ-induced diabetes inappropriate for studying islet
      allografts in swine.

PMID- 16421473
TI  - Long-term acceptance of fully allogeneic cardiac grafts by cotransplantation of
      vascularized thymus in miniature swine.
AB  - BACKGROUND: We have previously reported the ability of both thymokidney and
      vascularized thymic lobe (VTL) allografts to induce transplantation tolerance to
      renal allografts across a full major histocompatibility complex (MHC) mismatch in
      thymectomized miniature swine. However, whether vascularized thymus is capable of
      inducing tolerance to less tolerogeneic organs when it is transplanted
      simultaneously is not yet known. The present study investigates cardiac allograft
      survival and the mechanism of long-term acceptance in recipient swine following
      cotransplantation of VTL and cardiac grafts from fully MHC-mismatched donors.
      METHODS: Animals received a heart graft, a heart graft and a VTL, or a heart
      graft and a donor thymocyte infusion. Immunosuppressive regimens consisted of 12
      or 28 days of tacrolimus. RESULTS: All animals that received a VTL maintained
      their grafts significantly longer than their counterparts that received only a
      heart graft, and those receiving 28 days of tacrolimus maintained their heart
      grafts long-term. Recipients of a donor thymocyte infusion demonstrated slightly
      prolonged cardiac graft survival but all rejected their grafts, highlighting the
      importance of thymic stroma. Cytotoxic T-lymphocyte responses against third-party
      antigens by cells from tolerant animals showed restriction by both self and donor
      MHC, whereas responses of controls were restricted to self MHC only. The presence
      of donor dendritic cells in the VTL grafts and results of co-culture assays
      suggest that both central and regulatory mechanisms were involved in achieving
      long-term acceptance. CONCLUSION: This is the first demonstration of the long
      term acceptance of fully MHC-mismatched cardiac allografts in large animals.

PMID- 16421475
TI  - Influence of CYP3A5 gene polymorphisms of donor rather than recipient to
      tacrolimus individual dose requirement in liver transplantation.
AB  - BACKGROUND: Tacrolimus is a widely used immunosuppressant in organ
      transplantation, but it is characterized by a narrow therapeutic index and high
      interindividual variations of its pharmacokinetics. Tacrolimus is a substrate for
      CYP3A. It has been conjectured that CYP3A5 polymorphism is associated with
      tacrolimus pharmacokinetic variations. The objective of this study was to
      evaluate the contribution of polymorphisms of the donor and recipient CYP3A5 gene
      on tacrolimus disposition in liver transplantation. METHODS: Fifty-three liver
      transplant recipients treated with tacrolimus were enrolled in this study.
      Tacrolimus dosage and blood trough concentration were investigated at 1 week, 2
      weeks, and 1 month after transplantation. Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis was applied to determine the
      genotype of CYP3A5 gene. RESULTS: The concentration/dose (C/D) ratios in patients
      with *1/*1(*1/*3) genotype donor were significantly lower than in patients with
      *3/*3 genotype donor at 2 weeks (P = 0.036) and 1 month (P = 0.021), but not at 1
      week posttransplantation. Combination analysis showed that such significance
      still existed between CYP3A5 expressor group and nonexpressor group for both
      donor and recipient genotype. Also differences of C/D ratio between CYP3A5
      expressor and nonexpressor donors in nonexpressor recipients were larger than
      those between recipients in nonexpressor donors. CONCLUSION: The large
      interindividual variation of tacrolimus dose requirement is influenced by the
      metabolic activity of CYP3A5. Polymorphisms of the donor CYP3A5 gene seem to
      contribute more to such variation than the recipient. A larger population and
      further studies are needed to explore the exact mechanisms for tacrolimus
      pharmacokinetics.

PMID- 16421476
TI  - Randomized placebo-controlled study on the effects of losartan and carvedilol on
      albuminuria in renal transplant recipients.
AB  - BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin
      system in renal transplant recipients have been supposed but not finally proven.
      To shed more light on this issue, we performed a double-blind, placebo
      controlled, crossover study to evaluate the influence of the AT-1 angiotensin II
      receptor blocker, losartan, on the surrogate marker of kidney injury,
      albuminuria, in patients after renal transplantation. The safety of this therapy
      was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female),
      age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with
      hypertension and stable serum creatinine 123 +/- 4 micromol/L without
      proteinuria, completed the protocol. Each patient underwent two 8-week treatment
      periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in
      random order, allowing an 8-week placebo washout between treatments. The target
      office trough blood pressure was below 130/85 mmHg. RESULTS: The ambulatory blood
      pressure did not differ in the treatment periods. Losartan significantly reduced
      albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33
      v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically
      relevant decrease in hemoglobin level after losartan was observed (losartan: 129
      +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum
      potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels
      were unaffected. CONCLUSION: Losartan decreases microalbuminuria in renal
      transplant recipients with clinically minimal side effects.

PMID- 16421477
TI  - Thrombotic microangiopathy after lung transplantation.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) is a well-recognized complication
      after transplantation. The purpose of this study was to describe our center's
      experience with this complication after lung transplantation. METHODS: We
      retrospectively reviewed cases of TMA among patients who underwent lung
      transplantation between January 1, 1999 and December 31, 2003 (n = 257). The
      cases were characterized and the outcomes were analyzed. Univariate and
      multivariate Cox regression models were constructed to identify potential risk
      factors for TMA. RESULTS: Twenty-four cases of TMA developed in 20 recipients.
      Thirteen cases occurred in the setting of another illness and 11 cases were
      isolated complications. Multivariate Cox regression models identified female
      gender, history of TMA, and the immunosuppressive regimen as independent
      predictors of TMA. Maintenance immunosuppression with the combination of a
      calcineurin inhibitor and sirolimus carried a significantly higher risk of TMA
      than a calcineurin inhibitor alone. After the diagnosis of TMA, calcineurin
      inhibitors were stopped in 18 cases; however, in 6 cases in which the onset of
      TMA coincided with the addition of sirolimus to a calcineurin inhibitor, only
      sirolimus was discontinued. Plasmapheresis was performed for severe cases (n =
      10). TMA remitted in all cases, and an alternate calcineurin inhibitor was
      introduced in 14 cases. TMA recurred in 4 recipients, a median 253 days after the
      initial episode. The median survival after the onset of TMA was 377 days.
      CONCLUSION: TMA is a serious complication after lung transplantation, and the
      risk is highest when sirolimus is used in combination with a calcineurin
      inhibitor.

PMID- 16421478
TI  - Genetic detection of lymph node micrometastases: a selection criterion for liver
      transplantation in patients with liver metastases after colorectal cancer.
AB  - BACKGROUND: Liver transplantation for nonresectable liver metastases from
      colorectal cancer was abandoned in 1994 on account of high recurrence rates. The
      aim of this study was to investigate whether the genetic detection of
      micrometastases in histologically negative lymph nodes of the primary colon
      cancer could be applied to select patients for liver transplantation. METHODS: We
      analyzed 21 patients with colorectal cancer who had undergone liver
      transplantation between 1983 and 1994 for liver metastases. Eleven patients were
      histologically lymph node negative at the time of surgery; ten patients with
      lymph node metastases served as control group. DNA sequencing was used to screen
      tumor material for p53 and K-ras mutations. Mutant allele-specific amplification
      (MASA) was then used to search for micrometastases in DNA from regional lymph
      nodes of the primary colorectal cancer. RESULTS: p53 and K-ras mutations were
      detected in 12 (57%) and 3 (14%) of 21 patients in the colorectal cancer,
      respectively. The mutations were confirmed in the corresponding liver metastases.
      Of 11 patients with histologically negative lymph nodes, nine were eligible for
      MASA due to presence of p53 or K-ras mutation. MASA revealed six of nine patients
      to be genetically positive for micrometastases. Three patients were both
      genetically and histologically negative. These three patients showed a
      significantly longer overall survival (P = 0.011) of 4, 5, and 20 years,
      respectively. CONCLUSIONS: We conclude that the genetic detection of
      micrometastases by MASA could be a powerful prognostic indicator for selecting
      patients with colorectal liver metastases who could benefit from liver
      transplantation.

PMID- 16421479
TI  - Hypertension in heart and heart-lung transplanted children: does impaired
      baroreceptor function play a role?
AB  - BACKGROUND: Baroreceptor control of beat-to-beat blood pressure in heart and
      heart-lung-transplanted children is impaired. Time-related trends of baroreceptor
      function recovery are studied and a possible correlation of baroreflex impairment
      and systolic hypertension may give evidence for supplemental medical treatment of
      hypertension. METHODS: Seventeen patients (six female) 6.1 +/- 3.7 years (range
      0.8-13.0 years) after heart (n = 14) and heart-lung (n = 3) transplantation (TX)
      were studied. Twelve healthy children and 10 children after liver and bone marrow
      TX taking cyclosporine A (CyA) served as control groups 1 and 2, respectively.
      Baroreceptor sensitivity (BRS) was calculated from noninvasive systolic beat-to
      beat blood pressure (sBP) measurement during a resting phase and a tilt-table
      test. RESULTS: BRS was significantly impaired in the study group at rest and
      during tilting; mean sBP was slightly elevated. Significant difference between
      patients on CyA and healthy controls was not observed. Discrete recovery of BRS
      occurred after 4 years postTX with decreased sBP (n = 12 pts, BRS 6.78 +/- 7.44
      msec/mmHg, sBP 116.2 +/- 12.4 mmHg) when compared to a postTX time course of less
      than 4 years (n = 5 pts, BRS 4.02 +/- 4.21 msec/mmHg, sBP 122.0 +/- 6.7 mmHg, P =
      NS). CONCLUSION: BRS is disturbed after TX in children; four years postTX, a
      minimal recovery of BRS and a discrete reduction of sBP seem to occur. Those
      patients with a persistent low BRS and elevated sBP may profit from
      pharmacological influence in sympathovagal imbalance.

PMID- 16421480
TI  - Kidney transplantation from anti-HBc+ donors: results from a retrospective
      Italian study.
AB  - BACKGROUND: The risk of transmitting a hepatitis B virus (HBV) infection from
      donor kidneys with a past HBV serological profile may be negligible. Data on HBV
      transmission to kidney transplant recipients from donor organs that were anti
      HBc/HBsAg in Italy has not been previously reported. Anti-HBc testing in cadaver
      organ donors has been mandatory in Italy since 2002, when anti-HBc determinations
      were included in the National Guidelines for donor evaluation. Therefore, prior
      to that date kidney recipients from anti-HBc/HBsAg donors can be identified
      retrospectively where stored serum is available for testing. METHODS: The
      prevalence of anti-HBc Italian organ donors, the incidence of HBV transmission
      according to the recipients' HBV status (vaccinated, recovered, or naive), and
      the clinical impact (5-year graft and patient survival rates) in the North Italy
      Transplant program was evaluated by retrospectively screening for anti-HBc
      antibodies in the sera of cadaver kidney donors used in transplants from 1997 to
      1999. RESULTS: Two hundred and ten donors were found to have been anti-HBc. At
      the time of the study, no active infection was observed in any of the 344 HBsAg
      recipients, but 4/140 (2.86%) of the vaccinated recipients were found to have
      been anti-HBc/HBsAg. None of these patients, however, had any biochemical or
      clinical history of HBV infection. Patient and graft survival rates of anti-HBc
      or anti-HBc kidney recipients did not differ statistically. CONCLUSION: Kidney
      grafts from anti-HBc donors should be considered in all recipients because the
      benefit obtained from the transplantation out weighs the negligible risk of HBV
      transmission.

PMID- 16421481
TI  - T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients.
AB  - BACKGROUND: Kidney transplant patients given Campath-1H (Alemtuzumab)
      immunodepletion therapy and long-term rapamycin monotherapy have excellent graft
      survival and function at three years. As an initial step in understanding the
      characteristics of repopulated T lymphocytes in these patients, we performed
      several assays to assess alloreactivity. METHODS: We measured T-cell responses
      using CFSE-labeled recipient lymphocytes in a direct one-way MLR, and also
      analyzed the kinetics of expression of IFN-gamma. We examined the T-cell
      responses of Campath-treated transplant patients on monotherapy versus those
      treated with anti-CD25 (Basiliximab) induction therapy and maintenance
      immunosuppression consisting of cyclosporine A, mycophenolate mofetil, and
      steroids. RESULTS: On average, proliferative responses to donor antigen were
      equal between Campath and control groups. However, the Campath group displayed a
      greater response to third party compared to donor antigen (CD3 P = 0.04, CD4 P =
      0.07, CD8 P < 0.01), whereas the control group did not display a greater response
      to third party (CD3 P = 0.69, CD4 P = 0.72, CD8 P = 0.60). Interestingly, more
      Campath patients (4 of 15) than control patients (0 of 8) displayed donor
      specific unresponsiveness as gauged by IFN-gamma expression and T-cell
      proliferation (P = 0.15). CONCLUSIONS: These studies suggest that Campath-1H in
      conjunction with rapamycin monotherapy retains intact immune responses to third
      party alloantigen, yet may promote hyporesponsiveness to donor antigen.

PMID- 16421482
TI  - Rapamycin prolongs susceptibility of responding T cells to tolerance induction by
      CD8+ veto cells.
AB  - BACKGROUND: CD8 veto cells are an antigen-specific immunoregulatory cell type
      that induces tolerance by causing apoptosis in T cells that recognize antigens on
      the veto cell. However, responding T cells are only susceptible to veto based
      deletion for a 48-hour window, which represents a severe limitation to the use of
      veto cells as a cellular therapeutic. Several immunosuppresant drugs inhibit T
      cell differentiation at distinct points. We hypothesized that immunosuppresants,
      which arrest T cell differentiation, would maintain responding T cells in a
      vetoable state. METHODS: CD8 veto cells were generated from BALB/c (H-2) mice.
      The 2C transgenic mouse, which expresses a T cell receptor specific for L was
      used to visualize responding cells. Veto activity was measured by both
      visualizing apoptosis of the responding 2C T cells and by measuring a decrease in
      lysis of H-2 targets. Several immunosuppressant drugs were tested for their
      effect on veto cell activity. RESULTS: BALB/c veto cells exhibited a potent and
      antigen-specific deletion of 2C responder cells, but not mature 2C effectors. The
      addition of rapamycin significantly extended the window of opportunity to veto
      based deletion by preventing the responding 2C T cells from differentiating out
      of a vetoable state. CONCLUSION: These findings demonstrate that by utilizing
      rapamycin, the window of opportunity for veto-based induction of tolerance to
      transplantation antigens is significantly extended. This approach circumvents a
      serious obstacle in the development of veto cells as an efficacious cellular
      therapy to induce allospecific tolerance to transplantation antigens.

PMID- 16421483
TI  - Decay-accelerating factor prevents acute humoral rejection induced by low levels
      of anti-alphaGal natural antibodies.
AB  - BACKGROUND: Hyperacute and delayed vascular rejection due to natural antibodies
      (NAb) present major obstacles in pig-to-primate xenotransplantation. Although
      "supraphysiologic" expression of human complement regulatory proteins (CRPs) can
      prevent hyperacute rejection in discordant xenogenic recipients, their
      physiologic role in the homologous setting is undefined. We have evaluated the
      effect of the absence of decay-accelerating factor (DAF) on cardiac allograft
      rejection in the presence of different levels of antidonor antibodies (Ab).
      METHODS: DAF1-deficient (DAF KO; B6129F2 H-2) mice were used as heart graft
      donors to alpha1,3-galactosyltransferase deficient (GalT KO; B6, H-2) recipients.
      Heterotopic heart grafting was performed with or without presensitization. Graft
      survival, histology, and anti-alphaGal Ab levels were monitored. RESULTS: DAF
      knockout (KO) but not wild-type (WT) grafts showed hyperacute or acute humoral
      rejection in nonsensitized GalT KO mice with low levels of anti-alphaGal IgM NAb.
      However, humoral rejection of both DAF KO and DAF WT donor grafts occurred in
      presensitized GalT KO recipients. CONCLUSIONS: The expression of DAF prevents
      hyperacute rejection in mice with low titers of anti-alphaGal antibody. These
      studies demonstrate the physiologic role of DAF in preventing humoral rejection
      in the presence of low levels of NAb and have implications for transplantation of
      discordant vascularized xenografts.

PMID- 16421484
TI  - Survival benefit of asymptomatic cytomegalovirus reactivation after HLA-identical
      allogeneic peripheral blood stem cell transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) reactivation (CMV-R) is associated with
      increased morbidity after allogeneic stem cell transplantation (SCT). However,
      after the introduction of ganciclovir preemptive therapy, CMV-R can be
      successfully controlled if the recipient's immunity recovers. Although many
      investigations have already focused on CMV-R as a risk factor, data related to
      the impact of asymptomatic CMV-R on transplant outcomes is scarce. Accordingly,
      the present study analyzed the differences in the transplant outcomes the immune
      reconstitution according to the CMV-R after allogeneic PBSCT. METHODS: A total of
      76 patients undergoing allogeneic peripheral blood stem cell transplantation
      (PBSCT) were included in the current study. The transplant outcomes and immune
      reconstitution after 3, 6, and 12 months were analyzed according to the
      occurrence of CMV-R in 33 patients. RESULTS: The analysis revealed a favorable
      prognosis for the group with CMV-R compared to those without CMV-R: P = 0.0037
      for OS, P = 0.0204 for NRM, and P = 0.05 for the risk of relapse. CMV-R was also
      found to correlate to the lymphoid reconstitution (P = 0.024). In multivariate
      analyses, CMV-R was found to be a favorable prognostic factor in terms of OS (P =
      0.010, hazard ratio [HR] 2.948) and NRM (P = 0.05, HR 2.665), along with a higher
      transplant CD34 cell dose (P = 0.003 for OS, P = 0.002 for NRM), standard risk (P
      = 0.023 for OS), and acute GVHD grades 0-2 (P = 0.007 for NRM). CONCLUSION: In a
      PBSCT setting, CMV-R did not seem to be a poor prognostic factor in terms of OS
      and NRM, possibly due to the accelerated lymphoid immune reconstitution
      associated with CMV-R.

PMID- 16421486
TI  - Intravenous immunoglobulin as a treatment for BK virus associated nephropathy:
      one-year follow-up of renal allograft recipients.
AB  - BK virus associated nephropathy (BKVAN) has emerged as an important cause of
      renal allograft dysfunction and graft loss. Although several treatment strategies
      have been proposed, the rate of graft loss remains high. We studied the outcome
      of renal transplant patients with BKVAN treated with IVIG. After 11.4 +/- 3.9
      months (mean +/- SEM) from the time of transplantation, 8 renal allograft
      recipients were diagnosed with BKVAN. In addition to a reduction of
      immunosuppressive therapy, patients received 2 g/kg IVIG. After a mean follow-up
      of 15 months, all except one patient are currently off dialysis. In summary,
      after IVIG therapy, 88% of patients still have functioning grafts, although renal
      function continues to be impaired. The benefit of concomitant IVIG and reduction
      of immunosuppressive therapy in BKVAN needs to be further addressed in
      randomized, multicentered trials.

PMID- 16421485
TI  - An antagonist mutant IL-15/Fc promotes transplant tolerance.
AB  - BACKGROUND: IL-15 is a proinflammatory and antiapoptotic T-cell growth factor
      that plays an important role in a variety of autoimmune disorders and transplant
      rejection. To inhibit IL-15 function and to target IL-15 receptor (IL-15R)
      bearing cells, we have generated a unique lytic antagonistic mutant IL-15/Fc
      fusion protein (mIL-15/Fc). METHODS: In this study, we further examined the
      efficacy of mIL-15/Fc in preventing allograft rejection cross minor and major
      histocompatibility barriers. RESULTS: A short-course treatment with mIL-15/Fc
      fusion protein is sufficient to prevent cardiac allograft rejection and induce
      antigen-specific tolerance in minor histocompatibility complex-mismatched
      recipients, and permit prolonged cardiac allograft survival in fully MHC
      mismatched recipients. In addition, mIL-15/Fc treatment, in combination with a
      suboptimal dose of anti-CD154 antibody, confers permanent cardiac allograft
      engraftment in a fully MHC-mismatched mouse strain combination. In a murine islet
      allograft model, mIL-15/Fc monotherapy is capable to permit permanent allograft
      survival in 50% fully MHC-mismatched recipients. CONCLUSION: Immunochemistry
      studies demonstrated that prolonged graft survival was accompanied by reduced
      intragraft mononuclear cell infiltration and pro-inflammatory cytokine gene
      expression in the mIL-15/Fc treated recipients. Moreover, parallel experiments
      employing a mutated nonlytic IgG2a Fc demonstrate that the Fc portion of mIL
      15/Fc contributes to the overall efficacy of the molecule in vivo.

PMID- 16421487
TI  - Fatal pneumonia caused by Panton-Valentine Leucocidine-positive methicillin
      resistant Staphylococcus aureus (PVL-MRSA) transmitted from a healthy donor in
      living-donor liver transplantation.
AB  - Severe infections are the most dangerous complications in liver transplantation
      and their prevention is one of the major goals. A 60-year-old Saudi-Arabian
      female with decompensated hepatitis C liver cirrhosis received a right-lobe liver
      graft from her healthy daughter. After 9 days, the patient developed a rapidly
      progressive necrotizing pneumonia that was fatal in spite of extracorporal lung
      assist. The pneumonia was due to a Panton-Valentine Leucocidine-positive (PVL)
      methicillin-resistant Staphylococcus aureus (MRSA), or "community-acquired" MRSA,
      that had not been detectable in the patient preoperatively. The same strain of
      PVL-MRSA could be demonstrated in the nares of the asymptomatic donor, but not of
      other relatives, patients, or medical staff. These findings strongly suggest
      transmission of PVL-MRSA from the donor to the recipient. This case demonstrates
      a previously unknown, and potentially fatal, risk in living-donor liver
      transplantation: transmission of a severe infection from a healthy donor to the
      recipient.

PMID- 16421488
TI  - Five years of steroid sparing in renal transplantation with tacrolimus and
      mycophenolate mofetil.
AB  - Steroid sparing with tacrolimus and mycophenolate mofetil (MMF) is associated
      with good short-term renal transplant outcomes. However, late allograft
      dysfunction and failure remain concerns. In this study, 101 consecutive patients
      underwent renal transplantation with tacrolimus, MMF, and 7 days of
      corticosteroids only. After a median follow-up of 51 months (range 36-62),
      overall patient survival is 97%, and overall survival with graft function is 91%.
      The acute rejection rate at 12 months was 19%. Late rejection was uncommon, with
      only three further episodes beyond 12 months. Graft function was stable during
      the study, with a mean creatinine of 140 micromol/L and mean estimated creatinine
      clearance of 57 ml/min at the end of follow-up. Six patients developed
      posttransplant diabetes mellitus (three cases beyond 12 months). This steroid
      avoidance regimen is associated with excellent medium-term patient and graft
      outcomes, and a low incidence of side effects.

PMID- 16421489
TI  - Utilization of a liver allograft from a hepatitis B surface antigen positive
      donor.
AB  - With today's donor organ shortage, enhanced efforts must be made to utilize
      organs that previously would have been declined. We report a 26-year-old man with
      chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection who
      received a liver transplant from an HBsAg-positive donor. HBV viremia (6,281,185
      copies/ml) was seen early posttransplant despite lamivudine prophylaxis, but
      became negative with addition of adefovir. Virologic analysis revealed
      predominantly donor HBV strain immediately posttransplant. At 5 months there was
      an elevation of liver enzymes accompanied by histologic evidence of hepatitis. At
      this time, HCV-RNA was positive but HBV DNA was undetectable. Treatment with
      pegylated interferon and ribavirin resulted in sustained clearance of HCV RNA.
      Two years posttransplant, the patient has normal liver biochemistry and HCV and
      HBV viral load are undetectable with persistence of HBsAg. Our experience
      suggests that with effective antiviral therapy, the use of HBsAg seropositive
      donors is feasible in selected circumstances.

PMID- 16421490
TI  - Coccidioidal meningitis after liver transplantation in a nonendemic region: a
      case report.

PMID- 16421491
TI  - Posttransplant cerebral hemorrhage in a patient with familial amyloidotic
      polyneuropathy.

PMID- 16421492
TI  - Right renal vein extension with recipient left renal vein after laparoscopic
      donor nephrectomy.

PMID- 16421493
TI  - Interaction between tacrolimus and fumagillin in two kidney transplant
      recipients.

PMID- 16421494
TI  - Primary cytomegalovirus disease after five years of antiviral prophylaxis.

PMID- 16421496
TI  - Patient-specific daily pretreatment setup protocol using electronic portal
      imaging for radiation therapy.
AB  - The purpose of this study was to evaluate electronic portal imaging (EPI) as a
      means of identifying and correcting field displacement in patients with
      problematic external beam radiotherapy setups. Fourteen patients with problematic
      setups were identified for pretreatment daily EPI beam monitoring as part of a
      physician-directed therapist intervention protocol. Pretreatment EPIs were used
      to realign fields as necessary to bring the setup within the physician-prescribed
      tolerance level. For comparison, daily EPIs were available for 12 control
      patients who had no particular setup difficulties and for whom online beam
      realignment was not made. Anatomy-matching software was used to measure setup
      variation along medial-lateral, superior-inferior, and anterior-posterior axes.
      Online field realignment yielded a significant (p = 0.001) improvement when
      comparing initial and final setup variations. The mean standard deviation of
      setup displacement averaged over three axes was reduced from 6.4 mm to 3.1 mm
      after realignment. The final variation of protocol patients was comparable to
      that of control patients. In conclusion, EPI provided effective means to perform
      online beam realignment in a group of difficult-to-position patients. This
      procedure resulted in a reduction in setup displacement that was statistically
      significant, clinically relevant, and approached that of a more typical patient
      group.

PMID- 16421497
TI  - Image processing for IMRT QA dosimetry.
AB  - We have automated the determination of the placement location of the dosimetry
      ion chamber within intensity-modulated radiotherapy (IMRT) fields, as part of
      streamlining the entire IMRT quality assurance process. This paper describes the
      mathematical image-processing techniques to arrive at the appropriate measurement
      locations within the planar dose maps of the IMRT fields. A specific spot within
      the found region is identified based on its flatness, radiation magnitude,
      location, area, and the avoidance of the interleaf spaces. The techniques used
      include applying a Laplacian, dilation, erosion, region identification, and
      measurement point selection based on three parameters: the size of the erosion
      operator, the gradient, and the importance of the area of a region versus its
      magnitude. These three parameters are adjustable by the user. However, the first
      one requires tweaking in extremely rare occasions, the gradient requires rare
      adjustments, and the last parameter needs occasional fine-tuning. This algorithm
      has been tested in over 50 cases. In about 5% of cases, the algorithm does not
      find a measurement point due to the extremely steep and narrow regions within the
      fluence maps. In such cases, manual selection of a point is allowed by our code,
      which is also difficult to ascertain, since the fluence map does not yield itself
      to an appropriate measurement point selection.

PMID- 16421498
TI  - A method for deconvolution of integrated electronic portal images to obtain
      incident fluence for dose reconstruction.
AB  - A method to convert integrated electronic portal imaging device (EPID) images to
      fluence for the purpose of reconstructing the dose to a phantom is investigated
      here for simple open fields. Ultimately, the goal is to develop a method to
      reconstruct the dose to patients. The EPID images are transformed into incident
      intensity fluence by spatial filtering with a deconvolution kernel. The kernel
      uses a general mathematical form derived from a Monte Carlo calculation of the
      point spread function of an EPID. The deconvolution kernel is fitted using a
      downhill search algorithm that minimizes the difference between the reconstructed
      dose and the dose measured in water. The beam profile "horns" that are removed by
      the EPID calibration procedure are restored to the resulting images by direct
      multiplication using the measured in-air off-axis ratio. Applying the fitted
      kernel to an EPID image provides the incident fluence for that beam. This beam
      fluence is then entered into an independent dose calculation algorithm for
      phantom or patient dose reconstruction. The phantom dose was computed to an
      accuracy of 2.0% of the dmax dose at one standard deviation. The method is
      general and can possibly be applied to any EPID equipped with an integration
      mode. We demonstrate the application of the fitted kernel in two clinical IMRT
      cases.

PMID- 16421500
TI  - AAPM Task Group 103 report on peer review in clinical radiation oncology physics.
AB  - This report provides guidelines for a peer review process between two clinical
      radiation oncology physicists. While the Task Group's work was primarily focused
      on ensuring timely and productive independent reviews for physicists in solo
      practice, these guidelines may also be appropriate for physicists in a group
      setting, particularly when dispersed over multiple separate clinic locations. To
      ensure that such reviews enable a collegial exchange of professional ideas and
      productive critique of the entire clinical physics program, the reviews should
      not be used as an employee evaluation instrument by the employer. Such use is
      neither intended nor supported by this Task Group. Detailed guidelines are
      presented on the minimum content of such reviews, as well as a recommended format
      for reporting the findings of a review. In consideration of the full schedules
      faced by most clinical physicists, the process outlined herein was designed to be
      completed in one working day.

PMID- 16421499
TI  - Target localization for post-prostatectomy patients using CT and ultrasound image
      guidance.
AB  - We conducted a study comparing B-mode acquisition and targeting (BAT) ultrasound
      alignments based on CT data in the postoperative setting. CT scans were obtained
      with a Primatom CT-on-rails on nine patients. Two CT scans were obtained each
      week, while setup error was minimized by BAT ultrasounds. For the first three
      patients, a direct comparison was performed. For the next six patients, a
      template based on the shifts from the week 1 CT during treatment was used for
      subsequent setup. Comparison of isocenter shifts between the BAT ultrasound and
      CT was made by the difference, absolute difference, and improvement (using CT
      alignments as the reference technique). A total of 90 image comparisons were
      made. The average interfraction motion was 3.2 mm in the lateral, 3.0 mm in the
      longitudinal, and 5.1 mm in the AP direction. The results suggest that the
      CTbased ultrasound templates can improve the localization of the prostate bed
      when the initial displacements are greater than 4 mm. For initial displacements
      smaller than 4 mm, the technique neither improved nor worsened target
      localization. However, ultrasound alignments performed without the use of a
      template deteriorated patient positioning for two out of three patients,
      demonstrating that the use of a CT template was beneficial even at small initial
      displacements.

PMID- 16421501
TI  - Monte Carlo-based lung cancer treatment planning incorporating PET-defined target
      volumes.
AB  - Despite the well-known benefits of positron emission tomography (PET) imaging in
      lung cancer diagnosis and staging, the poor spatial resolution of PET has limited
      its use in radiotherapy planning. Methods used for segmenting tumor from normal
      tissue, such as threshold boundaries using a fraction of the standardized uptake
      value (SUV), are subject to uncertainties. The issue of respiratory motion in the
      thorax confounds the problem of accurate target definition. In this work, we
      evaluate how changing the PET-defined target volume by varying the threshold
      value in the segmentation process impacts target and normal lung tissue doses.
      For each of eight lung cancer patients we retrospectively generated multiple PET
      target volumes; each target volume corresponds to those voxels with intensities
      above a given threshold level, defined by a percentage of the maximum voxel
      intensity. PET-defined targets were compared to those from CT; CT targets
      comprise a composite volume generated from breath-hold inhale and exhale
      datasets; the CT dataset therefore also includes the extents of tumor motion.
      Treatment plans using Monte Carlo dose calculation were generated for all
      targets; the dose uniformity was approximately 100+/-5% within the internal
      target volume (ITV) (formed by a uniform 8-mm expansion of the composite gross
      target volume (GTV)). In all cases differences were observed in the generalized
      equivalent uniform doses (gEUDs) to the targets and in the mean lung doses (MLDs)
      and normal tissue complication probabilities (NTCPs) to the normal lung tissues.
      The magnitudes of the dose differences were found to depend on the target volume,
      location, and amount of irradiated normal lung tissue, and in many instances were
      clinically meaningful (greater than a single 2 Gy fraction). For those patients
      studied, results indicate that accurate dosimetry using PET volumes is highly
      dependent on accurate target segmentation. Further study with correlation to
      clinical outcome will be helpful in determining how to apply these various PET
      and CT volumes in treatment planning, to potentially improve local tumor control
      and reduce normal tissue toxicities.

PMID- 16421502
TI  - Technical and dosimetric considerations in IMRT treatment planning for large
      target volumes.
AB  - The maximum width of an intensity-modulated radiotherapy (IMRT) treatment field
      is usually smaller than the conventional maximum collimator opening because of
      design limitations inherent in some multileaf collimators (MLCs). To increase the
      effective field width, IMRT fluences can be split and delivered with multiple
      carriage positions. However, not all treatment-planning systems and MLCs support
      this technique, and if they do, the maximum field width in multiple carriage
      position delivery is still significantly less than the maximum collimator
      opening. For target volumes with dimensions exceeding the field size limit for
      multiple carriage position delivery, such as liver tumors or other malignancies
      in the abdominal cavity, IMRT treatment can be accomplished with multiple
      isocenters or with an extended treatment distance. To study dosimetric statistics
      of large field IMRT planning, an elliptical volume was chosen as a target within
      a cubic phantom centered at a depth of 7.5 cm. Multiple three-field plans (one AP
      and two oblique beams with 160 degrees between them to avoid parallel opposed
      geometry) with constraints designed to give 100% dose to the elliptical target
      were developed. Plans were designed with a single anterior field with dual
      carriage positions, or with the anterior field split into two fields with
      separate isocenters 8 cm apart with the beams being forcibly matched at the
      isocenter or with a 1 cm, 2 cm, 3 cm, and 4 cm overlap. The oblique beams were
      planned with a single carriage position in all cases. All beams had a nominal
      energy of 6 MV. In the dual isocenter plans, jaws were manually fixed and dose
      constraints remained unaltered. Dosimetric statistics were studied for plans
      developed for treatment delivery using both dynamic leaf motion (sliding window)
      and multiple static segments (step and shoot) with the number of segments varying
      from 5 to 30. All plans were analyzed based on the dose homogeneity in the
      isocenter plane, 2 cm anterior and 2 cm posterior to it, along with their
      corresponding dose-volume histograms (DVHs). All the dual isocenter plans had
      slight underdosage anterior to the match point and slight overdosage posterior to
      it, while the dual carriage plan had a nice blending of the dose distribution
      without the accompanying hot or cold spots. Based on the dose statistics, it was
      noted that the dual isocenter plans can be clinically acceptable if they have at
      least a 3-cm overlap. In the case of step and shoot IMRT, the number of segments
      used in a dual carriage plan was found to affect the overall plan dosimetric
      indices.

PMID- 16421503
TI  - New automated fluoroscopic systems for pediatric applications.
AB  - Pediatric patients are at higher risk to the adverse effects from exposure to
      ionizing radiation than adults. The smaller sizes of the anatomy and the reduced
      X-ray attenuation of the tissues provide special challenges. The goal of this
      effort is to investigate strategies for pediatric fluoroscopy in order to
      minimize the radiation exposure to these individuals, while maintaining effective
      diagnostic image quality. Modern fluoroscopy systems are often entirely automated
      and computer controlled. In this paper, various selectable and automated modes
      are examined to determine the influence of the fluoroscopy parameters upon the
      patient radiation exposures and image quality. These parameters include variable
      X-ray beam filters, automatic brightness control programs, starting kilovolt peak
      levels, fluoroscopic pulse rates, and other factors. Typical values of radiation
      exposure rates have been measured for a range of phantom thicknesses from 5 cm to
      20 cm of acrylic. Other factors that have been assessed include spatial
      resolution, low contrast discrimination, and temporal resolution. The selection
      menu for various procedures is based upon the examination type, anatomical
      region, and patient size. For pediatric patients, the automated system can employ
      additional filtration, special automatic brightness control curves, pulsed
      fluoroscopy, and other features to reduce the patient radiation exposures without
      significantly compromising the image quality. The benefits gained from an optimal
      selection of automated programs and settings for fluoroscopy include ease of
      operation, better image quality, and lower patient radiation exposures.

PMID- 16421504
TI  - Interobserver variation in cervical cancer tumor delineation for image-based
      radiotherapy planning among and within different specialties.
AB  - Radiation therapy for cervical cancer involves a team of specialists, including
      diagnostic radiologists (DRs), radiation oncologists (ROs), and medical
      physicists (MPs), to optimize imaging-based radiation therapy planning. The
      purpose of the study was to investigate the interobserver variations in tumor
      delineation on MR images of cervical cancer within the same and among different
      specialties. Twenty MRI cervical cancer studies were independently reviewed by
      two DRs, two ROs, and two MPs. For every study, each specialist contoured the
      tumor regions of interest (ROIs) on T2-weighted Turbo Spin Echo sagittal images
      on all slices containing tumor, and the total tumor volume was computed for
      statistical analysis. Analysis of variance (ANOVA) was used to compare the
      differences in tumor volume delineation among the observers. A graph of all tumor
      delineated volumes was generated, and differences between the maximum and minimum
      volumes over all the readers for each patient dataset were computed. Challenges
      during the evaluation process for tumor delineation were recorded for each
      specialist. Interobserver variations of delineated tumor volumes were significant
      (p < 0.01) among all observers based on a repeated measures ANOVA, which produced
      an F(5,95) = 3.55. The median difference between the maximum delineated volume
      and minimum delineated volume was 33.5 cm3 (which can be approximated by a sphere
      of 4.0 cm diameter) across all 20 patients. Challenges noted for tumor
      delineation included the following: (1) partial voluming by parametrial fat at
      the periphery of the uterus; (2) extension of the tumor into parametrial space;
      (3) similar signal intensity of structures proximal to the tumor such as ovaries,
      muscles, bladder wall, bowel loops, and pubic symphysis; (4) postradiation
      changes such as heterogeneity and necrosis; (5) susceptibility artifacts from
      bowels and vaginal tampons; (6) presence of other pathologies such as atypical
      myoma; (7) factors that affect pelvic anatomy, including the degree of bladder
      distension, bowel interposition, uterine malposition, retroversion, and
      descensus. Our limited study indicates significant interobserver variation in
      tumor delineation. Despite rapid progress in technology, which has improved the
      resolution and precision of image acquisition and the delivery of radiotherapy to
      the millimeter level, such "human" variations (at the centimeter level) may
      overshadow the gain from technical advancement and impact treatment planning.
      Strategies of standardization and training in tumor delineation need to be
      developed.

PMID- 16421506
TI  - Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and
      decreases edema formation in permanent middle cerebral artery occlusion.
AB  - Estrogen has been shown to protect against stroke-induced brain damage, yet the
      mechanism is unknown. During the early hours of stroke, cerebral edema forms as
      increased transport of Na and Cl from blood into brain occurs across an intact
      blood-brain barrier (BBB). We showed previously that a luminal BBB Na-K-Cl
      cotransporter is stimulated by hypoxia and arginine vasopressin (AVP), factors
      present during cerebral ischemia, and that inhibition of the cotransporter by
      intravenous bumetanide greatly reduces edema in rats subjected to permanent
      middle cerebral artery occlusion (MCAO). The present study was conducted to
      determine whether estrogen protects in stroke at least in part by reducing
      activity of the BBB cotransporter, thereby decreasing edema formation.
      Ovariectomized rats were subjected to 210 mins of permanent MCAO after 7-day or
      30-min pretreatment with 17beta-estradiol and then brain swelling and 2,3,5
      triphenyltetrazolium chloride staining were assessed as measures of brain edema
      and lesion volume, respectively. Diffusion-weighed imaging was used to monitor
      permanent MCAO-induced decreases in apparent diffusion coefficient (ADC) values,
      an index of changes in brain water distribution and mobility. Na-K-Cl
      cotransporter activity of cerebral microvascular endothelial cells (CMECs) was
      assessed as bumetanide-sensitive K influx and cotransporter abundance by Western
      blot analysis after estradiol treatment. Estradiol significantly decreased brain
      swelling and lesion volume and attenuated the decrease in ADC values during
      permanent MCAO. Estradiol also abolished CMEC cotransporter stimulation by
      chemical hypoxia or AVP and decreased cotransporter abundance. These findings
      support the hypothesis that estrogen attenuates stimulation of BBB Na-K-Cl
      cotransporter activity, reducing edema formation during stroke.

PMID- 16421507
TI  - Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects
      the brain by maintaining penumbral oxygenation in a rat model of transient focal
      cerebral ischemia.
AB  - Oxygen therapy for ischemic stroke remains controversial. Too much oxygen may
      lead to oxidative stress and free radical damage while too little oxygen will
      have minimal therapeutic effect. In vivo electron paramagnetic resonance (EPR)
      oximetry, which can measure localized interstitial partial oxygen (pO2), can
      monitor penumbral changes of pO2. Therefore, we used EPR to study the effects of
      oxygen therapy in a rat model of 90-mins middle cerebral artery occlusion (MCAO).
      We found that 95% normobaric O2 given during ischemia was able to maintain
      penumbral interstitial pO2 levels close to the preischemic value while it may
      cause a two-fold increase in penumbral pO2 level if given during reperfusion.
      Elevation of the penumbra pO2 to preischemic physiologic level during MCAO
      significantly reduced infarction volume, improved neurologic function, decreased
      the generation of reactive oxygen species (ROS), and reduced matrix
      metalloproteinase (MMP)-9 expression and caspase-8 cleavage in the penumbra
      tissue of rats brain treated with oxygen. These results suggest that maintaining
      penumbral oxygenation by normobaric oxygen treatment during ischemia lead to
      neuroprotection, which is further reflected by the decreased production of ROS,
      MMP-9, and caspase-8.

PMID- 16421508
TI  - Positron emission tomography of monoaminergic vesicular binding in aging and
      Parkinson disease.
AB  - The type-2 vesicular monoamine transporter (VMAT2) might serve as an objective
      biomarker of Parkinson disease (PD) severity. Thirty-one subjects with early
      stage PD and 75 normal subjects underwent continuous intravenous infusion of (+)
      [(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography (PET) imaging
      to estimate the striatal VMAT2 binding site density with equilibrium tracer
      modeling. Parkinson disease patients were evaluated clinically in the practically
      defined 'off' state with the Unified Parkinson Disease Rating Scale (UPDRS), the
      Hoehn and Yahr Scale (HY), and the Schwab and England Activities of Daily Living
      Scale (SE). In normal subjects there was age-related decline in striatal DTBZ
      binding, approximating 0.5% per year. In PD subjects, specific DTBZ binding was
      reduced in the caudate nucleus (CD; -44%), anterior putamen (-68%), and posterior
      putamen (PP; -77%). The PP-to-CD ratio of binding was reduced significantly in PD
      subjects. Dihydrotetrabenazine binding was also reduced by approximately 50% in
      the PD substantia nigra. Striatal binding reductions correlated significantly
      with PD duration and SE scores, but not with HY stage or with UPDRS motor
      subscale (UPDRS(III)) scores. Striatal and midbrain DTBZ binding was asymmetric
      in PD subjects, with greatest reductions contralateral to the most clinically
      affected limbs. There was significant correlation between asymmetry of DTBZ
      binding and clinical asymmetry measured with the UPDRS(III). In HY stage 1 and
      1.5 subjects (n=16), PP DTBZ binding contralateral to the clinically unaffected
      body side was reduced by 73%, indicating substantial preclinical nigrostriatal
      pathology in PD. We conclude that (+)-[(11)C]DTBZ-PET imaging displays many
      properties necessary of a PD biomarker.

PMID- 16421509
TI  - Hemodynamic impairment as a stimulus for functional brain reorganization.
AB  - We used functional magnetic resonance imaging to investigate whether hemispheral
      hemodynamic impairment can play an independent role in the functional
      reorganization of motor-related activity in the brain. Fourteen patients with
      large vessel occlusion but no infarct performed a simple motor task with the hand
      contralateral to the occluded vessel. Statistical parametric maps of regional
      activity were generated to compare the distribution of motor-related activity
      among patients with that of control subjects. Patients were classified into
      normal or abnormal cerebral hemodynamics on the basis of intracerebral vasomotor
      reactivity using transcranial Doppler and carbon dioxide inhalation. Controls and
      patients with normal vasomotor reactivity showed typical motor activity in
      contralateral motor areas. When the 9 patients with abnormal vasomotor reactivity
      were compared with the 14 control subjects in a single analysis, unique motor
      activation was identified in ipsilateral motor regions in the nonhypoperfused
      hemisphere. In a confirmatory analysis, blood oxygen level-dependent (BOLD)
      signal intensity was averaged in prespecified motor regions of interest. A
      significant group by hemisphere interaction was identified, driven by higher
      ipsilateral and lower contralateral hemisphere BOLD signal in patients with
      abnormal vasomotor reactivity compared with controls (F=12.40, P=0.002). The
      average ipsilateral motor region signal intensity was also significantly higher
      in the subgroup of patients with abnormal vasoreactivity and no TIA compared with
      controls (P=0.04). Our results suggest that hemodynamic impairment in one
      hemisphere, even in the absence of any focal lesion or any symptoms can be
      associated with a functional reorganization to the opposite hemisphere.

PMID- 16421510
TI  - Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex
      vivo HGF gene transfer with HSV-1 vector.
AB  - Occlusive cerebrovascular disease leads to brain ischemia that causes
      neurological deficits. Here we introduce a new strategy combining mesenchymal
      stromal cells (MSCs) and ex vivo hepatocyte growth factor (HGF) gene transferring
      with a multimutated herpes simplex virus type-1 vector in a rat transient middle
      cerebral artery occlusion (MCAO) model. Gene-transferred MSCs were
      intracerebrally transplanted into the rats' ischemic brains at 2 h (superacute)
      or 24 h (acute) after MCAO. Behavioral tests showed significant improvement of
      neurological deficits in the HGF-transferred MSCs (MSC-HGF)-treated group
      compared with the phosphate-buffered saline (PBS)-treated and MSCs-only-treated
      group. The significant difference of infarction areas on day 3 was detected only
      between the MSC-HGF group and the PBS group with the superacute treatment, but
      was detected among each group on day 14 with both transplantations. After the
      superacute transplantation, we detected abundant expression of HGF protein in the
      ischemic brain of the MSC-HGF group compared with others on day 1 after
      treatment, and it was maintained for at least 2 weeks. Furthermore, we determined
      that the increased expression of HGF was derived from the transferred HGF gene in
      gene-modified MSCs. The percentage of apoptosis-positive cells in the ischemic
      boundary zone (IBZ) was significantly decreased, while that of remaining neurons
      in the cortex of the IBZ was significantly increased in the MSC-HGF group
      compared with others. The present study shows that combined therapy is more
      therapeutically efficient than MSC cell therapy alone, and it may extend the
      therapeutic time window from superacute to acute phase.

PMID- 16421511
TI  - CNS microvascular pericytes exhibit multipotential stem cell activity.
AB  - It has been suggested that a vascular-like cell has multipotent regenerative and
      mesenchymal lineage relationships. The identity of this stem/progenitor cell has
      remained elusive. We report here that adult central nervous system (CNS)
      capillaries contain a distinct population of microvascular cells, the pericyte
      that are nestin/NG2 positive and in response to basic fibroblast growth factor
      (bFGF) differentiate into cells of neural lineage. In their microvascular
      location, pericytes express nestin and NG2 proteoglycan. In serum containing
      media primary (0 to 7 day old) CNS pericytes are nestin positive, NG2 positive,
      alpha smooth muscle actin (alphaSMA) positive, and do not bind the endothelial
      cell specific griffonia symplicifolia agglutinin (GSA). In serum containing
      media, pericytes do not undergo neurogenesis but are induced to express alphaSMA.
      In bFGF containing media without serum, CNS pericytes form small clusters and
      multicellular spheres. Differentiated spheres expressed neuronal and glial cell
      markers. After disruption and serial dilution, differentiated spheres were
      capable of self-renewal. When differentiated spheres were disrupted and cultured
      in the presence of serum, multiple adherent cell populations were identified by
      dual and triple immunocytochemistry. Cells expressing markers characteristic of
      pericytes, neurons, and glial cells were generated. Many of the cells exhibited
      dual expression of differentiation markers. With prolonged culture fully
      differentiated cells of neural lineage were present. Results indicate that adult
      CNS microvascular pericytes have neural stem cell capability.

PMID- 16421512
TI  - Monoamine oxidase A activity and norepinephrine level in hippocampus determine
      hyperwheel running in SPORTS rats.
AB  - An understanding of neurological mechanisms for wheel running by rodents,
      especially with high exercise activity, would be applicable to a strategy for
      promotion of exercise motivation in humans. One of several brain regions that are
      candidates for the regulation of physical exercise is the hippocampus. Here we
      examined the running activity of Spontaneously-Running-Tokushima-Shikoku (SPORTS)
      rat, a new animal model for high levels of wheel-running activity, and its
      relation with the hippocampal norepinephrine (NE) system including the levels of
      NE, adrenergic receptors, and degradation enzymes for monoamines. In the
      hippocampus of SPORTS rats, the level of NE in extracellular fluid was augmented,
      whereas the level in the homogenate of the whole tissue was decreased even for
      sedentary conditions. Elevated extracellular NE caused downregulation of alpha(2)
      adrenergic receptors in the hippocampus of SPORTS rats. Local administration of
      alpha(2)-adrenergic receptor antagonist yohimbine, but not of alpha(2)-agonist
      clonidine, into the hippocampus suppressed high running activity in SPORTS rats.
      The protein expression and the activity levels of monoamine oxidase A (MAOA), a
      critical enzyme for the degradation of NE, were decreased in the hippocampus of
      SPORTS rats to increase extracellular NE level. Thus, inhibition of oxidase
      activity in normal Wistar rats markedly increased wheel-running activity. These
      results indicate that decreased MAOA activity, elevation of extracellular NE, and
      alpha(2)-adrenergic receptors in the hippocampus determine the neural basis of
      the psychological regulation of exercise behavior in SPORTS rats.

PMID- 16421513
TI  - Further evidence for an association of 5-HTTLPR with intensity dependence of
      auditory-evoked potentials.
AB  - Intensity dependence of auditory-evoked potentials (IAEP) has been suggested as
      an indicator of central serotonergic neurotransmission. Two recent studies
      investigated a possible association of IAEP with a functional polymorphism in the
      transcriptional control region of the serotonin transporter gene (5-HTTLPR) that
      has a short (s) and a long (l) variant. Although both studies found an
      association between 5-HTTLPR and IAEP, Gallinat et al found l/l individuals to
      exhibit lower IAEP, whereas Strobel et al observed stronger IAEP in l/l
      individuals. These conflicting results require further evaluation and more
      attention needs to be paid to variables that are known to be confounded with the
      effects of IAEP and 5-HTTLPR. Using a paradigm comparable to Strobel et al, the
      present study analyzes the effect of 5-HTTLPR on IAEP in a healthy male student
      sample (N=91; age=23 years, SD=1.9) that was homogenous for most significant
      confounding variables. A stronger IAEP was shown in l/l individuals, irrespective
      of the method of IAEP parametrization. This also held at retest after 3 weeks in
      a subsample (N=18). Given the successful replication of Strobel et al, several
      possible reasons for conflicting results with regard to Gallinat et al are
      discussed. It is argued that the most significant difference between Gallinat et
      al on the one hand, and Strobel et al and this study on the other, is that
      different intensity ranges are used which impact IAEP. Therefore, this study
      encourages further analysis of dose dependence of results.

PMID- 16421514
TI  - Actions of novel antipsychotic agents on apomorphine-induced PPI disruption:
      influence of combined serotonin 5-HT1A receptor activation and dopamine D2
      receptor blockade.
AB  - The dopamine D1/D2 agonist apomorphine (0.63 mg/kg) disrupted prepulse inhibition
      (PPI) of acoustic startle in rats, a model of sensorimotor gating deficits
      observed in schizophrenia. All current antipsychotics, which antagonize D2
      receptors, prevent this apomorphine-induced deficit. A novel class of
      antipsychotics possesses, in addition to D2 antagonist property, various levels
      of 5-HT1A agonist activity. Considering that the latter itself produces PPI
      deficits, it appeared necessary to assess the potential of this novel class of
      antipsychotics to reverse apomorphine-PPI deficits. Potent D2 antagonists, like
      haloperidol (0.63-2.5 mg/kg), risperidone (0.63-10 mg/kg), and olanzapine (0.63
      40 mg/kg) prevented apomorphine PPI disruption. The atypical antipsychotics,
      clozapine (40 mg/kg), nemonapride (0.01-2.5 mg/kg), ziprasidone (10 mg/kg), and
      aripiprazole (0.01 and 10 mg/kg), which all exhibit 5-HT1A agonist properties,
      reversed PPI deficits at some doses only, whereas the anti-dyskinetic agent
      sarizotan (0.16-10 mg/kg), an efficacious 5-HT1A agonist, did not. New generation
      antipsychotics with marked 5-HT1A agonist properties, such as SLV313 and
      SSR181507 (0.0025-10 mg/kg and 0.16-10 mg/kg, respectively) did not reverse these
      deficits whereas bifeprunox (0.04-2.5 mg/kg) did. To reveal the contribution of 5
      HT1A agonist properties in the lack of effects of SLV313 and SSR181507, we
      pretreated rats with the 5-HT1A antagonist WAY100635 (0.63 mg/kg). Under these
      conditions, significant reversal of PPI deficit was observed, indicating that D2
      antagonist properties of SLV313 and SSR181507 are now sufficient to overcome the
      disruptive effects of apomorphine. To summarize, antipsychotics possessing
      agonist efficacy at 5-HT1A receptors exhibit diverse profiles against apomorphine
      induced PPI deficits, depending on the balance between D2 and 5-HT1A activities,
      suggesting that they may display distinct activity on some aspects of gating
      deficits in schizophrenic patients.

PMID- 16421515
TI  - DHEA, a neurosteroid, decreases cocaine self-administration and reinstatement of
      cocaine-seeking behavior in rats.
AB  - Dehydroepiandrosterone (DHEA), which can act as a potential antidepressant in
      both animals and humans, appears to lower distress involved with cocaine
      withdrawal. In fact, a role for neurosteroids in modulation of substance-seeking
      behavior is becoming increasingly clear. Therefore, we tested the effects of DHEA
      on the self-administration of cocaine (1 mg/kg/infusion) by rats. At maintenance,
      a relatively low dose of exogenous DHEA (2 mg/kg; i.p.) attenuated cocaine self
      administration after several days of chronic treatment. More than 2 weeks (19
      days) of daily DHEA injections were required to decrease the cocaine-seeking
      behavior of rats to less than 20% of their maintenance levels. DHEA does not seem
      to decrease cocaine self-administration by increasing the reinforcing properties
      of the drug, as indicated by a cocaine dose-response determination. After being
      subjected to extinction conditions in the presence of DHEA, rats demonstrated a
      minimal response to acute exposure to cocaine (10 mg/kg), which indicated a
      protective effect of DHEA on relapse to cocaine usage. Our results suggest a
      potential role for the neurosteroid DHEA in controlling cocaine-seeking behavior,
      by reducing both the desire for cocaine usage and the incidence of relapse.

PMID- 16421516
TI  - Free serum concentrations of the protein-bound retention solute p-cresol predict
      mortality in hemodialysis patients.
AB  - Based on in vitro data, protein-bound uremic retention solutes have increasingly
      been recognized to play a pathophysiological role in the uremic syndrome. p
      Cresol, a representative of this group of molecules, has been shown to be
      implicated in uremic immunodeficiency and endothelial dysfunction, potentially
      linking its serum levels to mortality. Thus far, however, no clinical information
      on this issue is available. To determine the relationship between p-cresol and
      all-cause mortality, 175 prevalent hemodialysis (HD) patients were enrolled in a
      prospective study. At baseline, serum levels of the water-soluble solutes urea,
      creatinine, and phosphate, the middle molecule beta2-microglobulin, total and
      free concentrations of the protein-bound solute p-cresol, and several risk
      factors for mortality were evaluated. During a median follow-up of 34 months, 60
      patients died. Baseline comorbidity (Davies score) (hazard ratio (HR), 1.49; 95%
      confidence interval (95% CI), 1.19-1.86), impaired nutritional status (HR, 4.22;
      95% CI, 2.15-8.29), time since initiation of dialysis (HR, 0.98; 95% CI, 0.97
      1.00), and higher free concentrations of the protein-bound solute p-cresol (HR,
      2.28; 95% CI, 1.12-4.64) were independently associated with mortality
      (multivariate Cox proportional hazards analysis). Our data suggest that free
      serum levels of p-cresol, a representative of the protein-bound uremic retention
      solutes, are associated with mortality in HD patients. These findings may
      encourage nephrologists to widen their field of interest beyond the scope of
      small water-soluble uremic solutes and middle molecules.

PMID- 16421517
TI  - Glucose and diabetes: effects on podocyte and glomerular p38MAPK, heat shock
      protein 25, and actin cytoskeleton.
AB  - Phosphorylated p38 (pp38) mitogen-activated protein kinase (MAPK) regulates heat
      shock protein 25 (HSP25), stabilizing fibrillar actin (FA) and preventing
      cleavage to G-actin (GA). Cultured podocytes (Pods) were exposed to glucose (5.5
      50 mM)+/-p38MAPK inhibitor SB202190 (SB) or control SB202474 to assess the
      effects on FA/GA and Pod structure. The relationship of p38MAPK with in vivo Pod
      structure and albuminuria (Ualb) was assessed in rats with streptozotocin (SZ)
      induced diabetes (DM) for 1 week, 1 month, and 4 months. High glucose induced
      concentration-dependent increases in pp38MAPK and phosphorylated HSP25 (pHSP25)
      maintained actin cytoskeleton. Inhibition by SB diminished pp38MAPK and pHSP25,
      decreased FA/GA, and altered FA and GA immunohistochemical appearance. In SZ-DM,
      glomerular pp38MAPK and biphosphorylated HSP25 were increased after 1 week,
      declining at 1 month, and at or below C values at 4 months. Glomerular FA/GA in
      DM was normal at 1 week, declining at 1 month, and low at 4 months.
      Ualb/creatinine was similar in DM vs C at 1 week, and increased at 1 and 4
      months. Morphometry demonstrated progressively diminishing slit pore density in
      DM over time, denoting evolving effacement. There were strong correlations
      between slit membrane density and both glomerular biphosphorylated HSP25 and ln
      Ualb/cr ratio. The data suggest that increased pp38MAPK and pHSP25 comprise an
      acute adaptation to glycemic stress. Later depletion of DM may contribute to Pod
      structural alterations and Ualb.

PMID- 16421518
TI  - Cognitive and neuropsychiatric consequences of endocannabinoid signaling
      dysfunction.

PMID- 16421519
TI  - The highs and lows of scientific conferences.
AB  - What are the main characteristics of scientific conferences and what
      distinguishes the successful meetings from the less successful? Here, semi
      seriously, I present a set of observations and suggestions that are organized
      into categories (such as big versus little conferences and long versus short
      conferences) and, for each category, I award the new meeting Oscars - the
      Georges.

PMID- 16421520
TI  - MAPKAP kinases - MKs - two's company, three's a crowd.
AB  - Downstream of mitogen-activated protein kinases (MAPKs), three structurally
      related MAPK-activated protein kinases (MAPKAPKs or MKs) - MK2, MK3 and MK5 -
      signal to diverse cellular targets. Although there is no known common function
      for all three MKs, these kinases are involved in important processes: MKs
      regulate gene expression at the transcriptional and post-transcriptional level,
      control cytoskeletal architecture and cell-cycle progression, and are implicated
      in inflammation and cancer.

PMID- 16421524
TI  - Standards for papers on cloning.

PMID- 16421525
TI  - Circulation challenge.

PMID- 16421526
TI  - A new ERA?

PMID- 16421528
TI  - Doctor admits Lancet study is fiction.

PMID- 16421529
TI  - Alarms ring over bird flu mutations.

PMID- 16421531
TI  - Snapshot: cloudshine is a stellar snap for Harvard duo.

PMID- 16421530
TI  - Will Germany choose a fair elite?

PMID- 16421532
TI  - Astronomers told to cut it out.

PMID- 16421533
TI  - Journals submit to scrutiny of their peer-review process.

PMID- 16421535
TI  - Promises to clean up industry fail to convince.

PMID- 16421536
TI  - Stress makes medics ever gloomier.

PMID- 16421539
TI  - Climate change: a sea change.

PMID- 16421540
TI  - Palaeontology: hooked on fossils.

PMID- 16421542
TI  - Hwang scandal hits Korean biotech hard.

PMID- 16421543
TI  - Humour of gene names lost in translation to patients.

PMID- 16421545
TI  - Value of high-protein diet is clearer than drawbacks.

PMID- 16421546
TI  - Risks of resurrecting 1918 flu virus outweigh benefits.

PMID- 16421547
TI  - Experiments in social responsibility.

PMID- 16421552
TI  - Condensed-matter physics: great moments in disorder.

PMID- 16421553
TI  - Cancer biology: signatures guide drug choice.

PMID- 16421554
TI  - Atmospheric chemistry: biogenic bromine.

PMID- 16421556
TI  - Plant biology: abscisic acid in bloom.

PMID- 16421557
TI  - Chemical ecology: in defence of maize.

PMID- 16421558
TI  - Nuclear physics: odd couple decays.

PMID- 16421559
TI  - Obituary: Theodore H. Bullock (1915-2005).

PMID- 16421560
TI  - Superplastic carbon nanotubes.
AB  - The theoretical maximum tensile strain--that is, elongation--of a single-walled
      carbon nanotube is almost 20%, but in practice only 6% is achieved. Here we show
      that, at high temperatures, individual single-walled carbon nanotubes can undergo
      superplastic deformation, becoming nearly 280% longer and 15 times narrower
      before breaking. This superplastic deformation is the result of the nucleation
      and motion of kinks in the structure, and could prove useful in helping to
      strengthen and toughen ceramics and other nanocomposites at high temperatures.

PMID- 16421561
TI  - A brain-specific microRNA regulates dendritic spine development.
AB  - MicroRNAs are small, non-coding RNAs that control the translation of target
      messenger RNAs, thereby regulating critical aspects of plant and animal
      development. In the mammalian nervous system, the spatiotemporal control of mRNA
      translation has an important role in synaptic development and plasticity.
      Although a number of microRNAs have been isolated from the mammalian brain,
      neither the specific microRNAs that regulate synapse function nor their target
      mRNAs have been identified. Here we show that a brain-specific microRNA, miR-134,
      is localized to the synapto-dendritic compartment of rat hippocampal neurons and
      negatively regulates the size of dendritic spines--postsynaptic sites of
      excitatory synaptic transmission. This effect is mediated by miR-134 inhibition
      of the translation of an mRNA encoding a protein kinase, Limk1, that controls
      spine development. Exposure of neurons to extracellular stimuli such as brain
      derived neurotrophic factor relieves miR-134 inhibition of Limk1 translation and
      in this way may contribute to synaptic development, maturation and/or plasticity.

PMID- 16421562
TI  - The RNA-binding protein FCA is an abscisic acid receptor.
AB  - The phytohormone abscisic acid (ABA) regulates various physiological processes in
      plants. The molecular mechanisms by which this is achieved are not fully
      understood. Genetic approaches have characterized several downstream components
      of ABA signalling, but a receptor for ABA has remained elusive. Although studies
      indicate that several ABA response genes encode RNA-binding or RNA-processing
      proteins, none has been found to be functional in binding ABA. Here we show that
      FCA, an RNA-binding protein involved in flowering, binds ABA with high affinity
      in an interaction that is stereospecific and follows receptor kinetics. The
      interaction between FCA and ABA has molecular effects on downstream events in the
      autonomous floral pathway and, consequently, on the ability of the plant to
      undergo transition to flowering. We further show that ABA binding exerts a direct
      control on the FCA-mediated processing of precursor messenger RNA. Our results
      indicate that FCA is an ABA receptor involved in RNA metabolism and in
      controlling flowering time.

PMID- 16421563
TI  - A late Miocene dust shower from the break-up of an asteroid in the main belt.
AB  - Throughout the history of the Solar System, Earth has been bombarded by
      interplanetary dust particles (IDPs), which are asteroid and comet fragments of
      diameter approximately 1-1,000 microm. The IDP flux is believed to be in quasi
      steady state: particles created by episodic main belt collisions or cometary
      fragmentation replace those removed by comminution, dynamical ejection, and
      planetary or solar impact. Because IDPs are rich in 3He, seafloor sediment 3He
      concentrations provide a unique means of probing the major events that have
      affected the IDP flux and its source bodies over geological timescales. Here we
      report that collisional disruption of the >150-km-diameter asteroid that created
      the Veritas family 8.3 +/- 0.5 Myr ago also produced a transient increase in the
      flux of interplanetary dust-derived 3He. The increase began at 8.2 +/- 0.1 Myr
      ago, reached a maximum of approximately 4 times pre-event levels, and dissipated
      over approximately 1.5 Myr. The terrestrial IDP accretion rate was overwhelmingly
      dominated by Veritas family fragments during the late Miocene. No other event of
      this magnitude over the past approximately 10(8) yr has been deduced from main
      belt asteroid orbits. One remarkably similar event is present in the 3He record
      35 Myr ago, but its origin by comet shower or asteroid collision remains
      uncertain.

PMID- 16421564
TI  - Proton-proton correlations observed in two-proton radioactivity of 94Ag.
AB  - The stability and spontaneous decay of naturally occurring atomic nuclei have
      been much studied ever since Becquerel discovered natural radioactivity in 1896.
      In 1960, proton-rich nuclei with an odd or an even atomic number Z were predicted
      to decay through one- and two-proton radioactivity, respectively. The
      experimental observation of one-proton radioactivity was first reported in 1982,
      and two-proton radioactivity has now also been detected by experimentally
      studying the decay properties of 45Fe (refs 3, 4) and 54Zn (ref. 5). Here we
      report proton-proton correlations observed during the radioactive decay of a
      spinning long-lived state of the lightest known isotope of silver, 94Ag, which is
      known to undergo one-proton decay. We infer from these correlations that the long
      lived state must also decay through simultaneous two-proton emission, making 94Ag
      the first nucleus to exhibit one- as well as two-proton radioactivity. We
      attribute the two-proton emission behaviour and the unexpectedly large
      probability for this decay mechanism to a very large deformation of the parent
      nucleus into a prolate (cigar-like) shape, which facilitates emission of protons
      either from the same or from opposite ends of the 'cigar'.

PMID- 16421565
TI  - Artificial 'spin ice' in a geometrically frustrated lattice of nanoscale
      ferromagnetic islands.
AB  - Frustration, defined as a competition between interactions such that not all of
      them can be satisfied, is important in systems ranging from neural networks to
      structural glasses. Geometrical frustration, which arises from the topology of a
      well-ordered structure rather than from disorder, has recently become a topic of
      considerable interest. In particular, geometrical frustration among spins in
      magnetic materials can lead to exotic low-temperature states, including 'spin
      ice', in which the local moments mimic the frustration of hydrogen ion positions
      in frozen water. Here we report an artificial geometrically frustrated magnet
      based on an array of lithographically fabricated single-domain ferromagnetic
      islands. The islands are arranged such that the dipole interactions create a two
      dimensional analogue to spin ice. Images of the magnetic moments of individual
      elements in this correlated system allow us to study the local accommodation of
      frustration. We see both ice-like short-range correlations and an absence of long
      range correlations, behaviour which is strikingly similar to the low-temperature
      state of spin ice. These results demonstrate that artificial frustrated magnets
      can provide an uncharted arena in which the physics of frustration can be
      directly visualized.

PMID- 16421566
TI  - Dynamical fracture instabilities due to local hyperelasticity at crack tips.
AB  - As the speed of a crack propagating through a brittle material increases, a
      dynamical instability leads to an increased roughening of the fracture surface.
      Cracks moving at low speeds create atomically flat mirror-like surfaces; at
      higher speeds, rougher, less reflective ('mist') and finally very rough,
      irregularly faceted ('hackle') surfaces are formed. The behaviour is observed in
      many different brittle materials, but the underlying physical principles, though
      extensively debated, remain unresolved. Most existing theories of fracture assume
      a linear elastic stress-strain law. However, the relation between stress and
      strain in real solids is strongly nonlinear due to large deformations near a
      moving crack tip, a phenomenon referred to as hyperelasticity. Here we use
      massively parallel large-scale atomistic simulations--employing a simple
      atomistic material model that allows a systematic transition from linear elastic
      to strongly nonlinear behaviour--to show that hyperelasticity plays a governing
      role in the onset of the instability. We report a generalized model that
      describes the onset of instability as a competition between different mechanisms
      controlled by the local stress field and local energy flow near the crack tip.
      Our results indicate that such instabilities are intrinsic to dynamical fracture
      and they help to explain a range of controversial experimental and computational
      results.

PMID- 16421567
TI  - Low sea level rise projections from mountain glaciers and icecaps under global
      warming.
AB  - The mean sea level has been projected to rise in the 21st century as a result of
      global warming. Such projections of sea level change depend on estimated future
      greenhouse emissions and on differing models, but model-average results from a
      mid-range scenario (A1B) suggests a 0.387-m rise by 2100 (refs 1, 2). The largest
      contributions to sea level rise are estimated to come from thermal expansion
      (0.288 m) and the melting of mountain glaciers and icecaps (0.106 m), with
      smaller inputs from Greenland (0.024 m) and Antarctica (- 0.074 m). Here we apply
      a melt model and a geometric volume model to our lower estimate of ice volume and
      assess the contribution of glaciers to sea level rise, excluding those in
      Greenland and Antarctica. We provide the first separate assessment of melt
      contributions from mountain glaciers and icecaps, as well as an improved
      treatment of volume shrinkage. We find that icecaps melt more slowly than
      mountain glaciers, whose area declines rapidly in the 21st century, making
      glaciers a limiting source for ice melt. Using two climate models, we project sea
      level rise due to melting of mountain glaciers and icecaps to be 0.046 and 0.051
      m by 2100, about half that of previous projections.

PMID- 16421568
TI  - Thallium isotopic evidence for ferromanganese sediments in the mantle source of
      Hawaiian basalts.
AB  - Ocean island basalts are generally thought to be the surface expression of mantle
      plumes, but the nature of the components in the source regions of such mantle
      plumes is a subject of long-standing debate. The lavas erupted at Hawaii have
      attracted particular attention, as it has been proposed that coupled 186Os and
      187Os anomalies reflect interaction with the Earth's metallic core. It has
      recently been suggested, however, that such variations could also result from
      addition of oceanic ferromanganese sediments to the mantle source of these lavas.
      Here we show that Hawaiian picrites with osmium isotope anomalies also exhibit
      pronounced thallium isotope variations, which are coupled with caesium/thallium
      ratios that extend to values much lower than commonly observed for mantle-derived
      rocks. This correlation cannot be created by admixing of core material, and is
      best explained by the addition of ferromanganese sediments into the Hawaii mantle
      source region. However, the lack of correlation between thallium and osmium
      isotopes and the high thallium/osmium ratios of ferromanganese sediments preclude
      a sedimentary origin for the osmium isotope anomalies, and leaves core-mantle
      interaction as a viable explanation for the osmium isotope variations of the
      Hawaiian picrites.

PMID- 16421569
TI  - Tetrapod-like middle ear architecture in a Devonian fish.
AB  - Few fossils show the incipient stages of complex morphological transformations.
      For example, the earliest stages in the remodelling of the spiracular tract and
      suspensorium (jaw suspension) of osteolepiform fishes into the middle ear of
      tetrapods have remained elusive. The most primitive known tetrapods show a middle
      ear architecture that is very different from osteolepiforms such as
      Eusthenopteron, with little indication of how this transformation took place.
      Here we present an analysis of tetrapod middle ear origins that is based on a
      detailed study of Panderichthys, the immediate sister taxon of tetrapods. We show
      that the spiracular region is radically transformed from osteolepiforms and
      represents the earliest stages in the origin of the tetrapod middle ear
      architecture. The posterior palatoquadrate of Panderichthys is completely
      tetrapod-like and defines a similarly tetrapod-like spiracular tract. The
      hyomandibula has lost its distal portion, representing a previously unrecognized
      advance towards a stapes-like morphology. This spiracular specialization suggests
      that the middle ear of early tetrapods evolved initially as part of a spiracular
      breathing apparatus.

PMID- 16421570
TI  - Reduced mixing generates oscillations and chaos in the oceanic deep chlorophyll
      maximum.
AB  - Deep chlorophyll maxima (DCMs) are widespread in large parts of the world's
      oceans. These deep layers of high chlorophyll concentration reflect a compromise
      of phytoplankton growth exposed to two opposing resource gradients: light
      supplied from above and nutrients supplied from below. It is often argued that
      DCMs are stable features. Here we show, however, that reduced vertical mixing can
      generate oscillations and chaos in phytoplankton biomass and species composition
      of DCMs. These fluctuations are caused by a difference in the timescales of two
      processes: (1) rapid export of sinking plankton, withdrawing nutrients from the
      euphotic zone and (2) a slow upward flux of nutrients fuelling new phytoplankton
      production. Climate models predict that global warming will reduce vertical
      mixing in the oceans. Our model indicates that reduced mixing will generate more
      variability in DCMs, thereby enhancing variability in oceanic primary production
      and in carbon export into the ocean interior.

PMID- 16421572
TI  - Top-down gain control of the auditory space map by gaze control circuitry in the
      barn owl.
AB  - High-level circuits in the brain that control the direction of gaze are
      intimately linked with the control of visual spatial attention. Immediately
      before an animal directs its gaze towards a stimulus, both psychophysical
      sensitivity to that visual stimulus and the responsiveness of high-order neurons
      in the cerebral cortex that represent the stimulus increase dramatically.
      Equivalent effects on behavioural sensitivity and neuronal responsiveness to
      visual stimuli result from focal electrical microstimulation of gaze control
      centres in monkeys. Whether the gaze control system modulates neuronal
      responsiveness in sensory modalities other than vision is unknown. Here we show
      that electrical microstimulation applied to gaze control circuitry in the
      forebrain of barn owls regulates the gain of midbrain auditory responses in an
      attention-like manner. When the forebrain circuit was activated, midbrain
      responses to auditory stimuli at the location encoded by the forebrain site were
      enhanced and spatial selectivity was sharpened. The same stimulation suppressed
      responses to auditory stimuli represented at other locations in the midbrain map.
      Such space-specific, top-down regulation of auditory responses by gaze control
      circuitry in the barn owl suggests that the central nervous system uses a common
      strategy for dynamically regulating sensory gain that applies across modalities,
      brain areas and classes of vertebrate species. This approach provides a path for
      discovering mechanisms that underlie top-down gain control in the central nervous
      system.

PMID- 16421571
TI  - DNA sequence and analysis of human chromosome 8.
AB  - The International Human Genome Sequencing Consortium (IHGSC) recently completed a
      sequence of the human genome. As part of this project, we have focused on
      chromosome 8. Although some chromosomes exhibit extreme characteristics in terms
      of length, gene content, repeat content and fraction segmentally duplicated,
      chromosome 8 is distinctly typical in character, being very close to the genome
      median in each of these aspects. This work describes a finished sequence and gene
      catalogue for the chromosome, which represents just over 5% of the euchromatic
      human genome. A unique feature of the chromosome is a vast region of
      approximately 15 megabases on distal 8p that appears to have a strikingly high
      mutation rate, which has accelerated in the hominids relative to other sequenced
      mammals. This fast-evolving region contains a number of genes related to innate
      immunity and the nervous system, including loci that appear to be under positive
      selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene
      that may have contributed to the evolution of expanded brain size in the great
      apes. The data from chromosome 8 should allow a better understanding of both
      normal and disease biology and genome evolution.

PMID- 16421573
TI  - Constant darkness is a circadian metabolic signal in mammals.
AB  - Environmental light is the 'zeitgeber' (time-giver) of circadian behaviour.
      Constant darkness is considered a 'free-running' circadian state. Mammals
      encounter constant darkness during hibernation. Ablation of the master clock
      synchronizer, the suprachiasmatic nucleus, abolishes torpor, a hibernation-like
      state, implicating the circadian clock in this phenomenon. Here we report a
      mechanism by which constant darkness regulates the gene expression of fat
      catabolic enzymes in mice. Genes for murine procolipase (mClps) and pancreatic
      lipase-related protein 2 (mPlrp2) are activated in a circadian manner in
      peripheral organs during 12 h dark:12 h dark (DD) but not light-dark (LD) cycles.
      This mechanism is deregulated in circadian-deficient mPer1-/-/mPer2m/m mice. We
      identified circadian-regulated 5'-AMP, which is elevated in the blood of DD mice,
      as a key mediator of this response. Synthetic 5'-AMP induced torpor and mClps
      expression in LD animals. Torpor induced by metabolic stress was associated with
      elevated 5'-AMP levels in DD mice. Levels of glucose and non-esterified fatty
      acid in the blood are reversed in DD and LD mice. Induction of mClps expression
      by 5'-AMP in LD mice was reciprocally linked to blood glucose levels. Our
      findings uncover a circadian metabolic rhythm in mammals.

PMID- 16421574
TI  - Oscillations of cyclic AMP in hormone-stimulated insulin-secreting beta-cells.
AB  - Cyclic AMP is a ubiquitous second messenger that transduces signals from a
      variety of cell surface receptors to regulate diverse cellular functions,
      including secretion, metabolism and gene transcription. In pancreatic beta-cells,
      cAMP potentiates Ca2+-dependent exocytosis and mediates the stimulation of
      insulin release exerted by the hormones glucagon and glucagon-like peptide-1 (GLP
      1) (refs 4, 5-6). Whereas Ca2+ signals have been extensively characterized and
      shown to involve oscillations important for the temporal control of insulin
      secretion, the kinetics of receptor-triggered cAMP signals is unknown. Here we
      introduce a new ratiometric evanescent-wave-microscopy approach to measure cAMP
      concentration beneath the plasma membrane, and show that insulin-secreting beta
      cells respond to glucagon and GLP-1 with marked cAMP oscillations. Simultaneous
      measurements of intracellular Ca2+ concentration revealed that the two messengers
      are interlinked and reinforce each other. Moreover, cAMP oscillations are capable
      of inducing rapid on-off Ca2+ responses, but only sustained elevation of cAMP
      concentration induces nuclear translocation of the catalytic subunit of the cAMP
      dependent protein kinase. Our results establish a new signalling mode for cAMP
      and indicate that temporal encoding of cAMP signals might constitute a basis for
      differential regulation of downstream cellular targets.

PMID- 16421578
TI  - Molecular cross-fertilization.

PMID- 16421576
TI  - Empathic neural responses are modulated by the perceived fairness of others.
AB  - The neural processes underlying empathy are a subject of intense interest within
      the social neurosciences. However, very little is known about how brain empathic
      responses are modulated by the affective link between individuals. We show here
      that empathic responses are modulated by learned preferences, a result consistent
      with economic models of social preferences. We engaged male and female volunteers
      in an economic game, in which two confederates played fairly or unfairly, and
      then measured brain activity with functional magnetic resonance imaging while
      these same volunteers observed the confederates receiving pain. Both sexes
      exhibited empathy-related activation in pain-related brain areas (fronto-insular
      and anterior cingulate cortices) towards fair players. However, these empathy
      related responses were significantly reduced in males when observing an unfair
      person receiving pain. This effect was accompanied by increased activation in
      reward-related areas, correlated with an expressed desire for revenge. We
      conclude that in men (at least) empathic responses are shaped by valuation of
      other people's social behaviour, such that they empathize with fair opponents
      while favouring the physical punishment of unfair opponents, a finding that
      echoes recent evidence for altruistic punishment.

PMID- 16421579
TI  - Challenges facing the biologist doing chemical genetics.
AB  - The goal of high-throughput screening (HTS) from the perspective of the biologist
      is to identify a highly specific small molecule that can be used to inhibit a
      protein in its normal biological context. Although several useful small molecules
      have been identified with HTS, there are many challenges to be considered when
      contemplating a screen, especially by those unfamiliar with chemical biology.

PMID- 16421580
TI  - Symbiosis in chemistry and biology.
AB  - What do organic synthesis, mechanistic enzymology, structural biology and
      glycoscience have in common? They all span chemistry and biology, benefit from
      and contribute to multidisciplinary approaches, and were up for discussion at a
      recent symposium in Dublin.

PMID- 16421581
TI  - Inhibitors of Bcr-abl... breaking new ground again.

PMID- 16421582
TI  - Getting under wraps: alkylating DNA in the nucleosome.

PMID- 16421583
TI  - Michaelis-Menten is dead, long live Michaelis-Menten!

PMID- 16421584
TI  - Sweet insights into learning and memory.

PMID- 16421586
TI  - Rethinking 'secondary' metabolism: physiological roles for phenazine antibiotics.
AB  - Microorganisms exist in the environment as multicellular communities that face
      the challenge of surviving under nutrient-limited conditions. Chemical
      communication is an essential part of the way in which these populations
      coordinate their behavior, and there has been an explosion of understanding in
      recent years regarding how this is accomplished. Much less, however, is
      understood about the way these communities sustain their metabolism. Bacteria of
      the genus Pseudomonas are ubiquitous, and are distinguished by their production
      of colorful secondary metabolites called phenazines. In this article, we suggest
      that phenazines, which are produced under conditions of high cell density and
      nutrient limitation, may be important for the persistence of pseudomonads in the
      environment.

PMID- 16421588
TI  - A green fluorescent protein-expressing murine tumour but not its wild-type
      counterpart is cured by photodynamic therapy.
AB  - The ideal cancer treatment should both destroy the primary tumour and at the same
      time educate the immune system to recognise the tumour as foreign so that distant
      metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v.
      administration of photosensitisers followed by illumination of the tumour with
      red light producing reactive oxygen species that eventually cause vascular
      shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is
      stimulated after PDT due to the acute inflammatory response, generation of tumour
      specific antigens, and induction of heat-shock proteins. Green fluorescent
      protein (GFP) is used as an optical reporter to noninvasively image the
      progression of mouse tumours, and in addition, may act as a foreign (jellyfish)
      antigen. We asked whether GFP-expressing tumours could be used to monitor the
      response of tumour-bearing mice to PDT, and whether the tumour response differed
      when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1
      or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of
      C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with
      benzoporphyrin derivative and a short drug-light interval. There were complete
      cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all
      recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a
      rechallenge with wild-type RIF-1 cells grew significantly slower. There was also
      slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours
      were surgically removed. There was a low rate of PDT cure of tumours when RIF-1
      cells were transduced with an empty retroviral vector. The presence of antibodies
      against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT
      can then stimulate a long-term memory immune response.

PMID- 16421589
TI  - The telomeric PARP, tankyrases, as targets for cancer therapy.
AB  - The requirement for the maintenance of telomeres by telomerase by most cancer
      cells for continued proliferation is a target in anticancer strategies.
      Tankyrases are poly(ADP-ribose) polymerases that enhance telomerase access to
      telomeres. Tankyrase 1 modulates telomerase inhibition in human cancer cells and
      is reviewed in this report as a potential telomere-directed anticancer target.

PMID- 16421590
TI  - Pathological complete response and residual DCIS following neoadjuvant
      chemotherapy for breast carcinoma.
AB  - Patients who have no residual invasive cancer following neoadjuvant chemotherapy
      for breast carcinoma have a better overall survival than those with residual
      disease. Many classification systems assessing pathological response to
      neoadjuvant chemotherapy include residual ductal carcinoma in situ (DCIS) only in
      the definition of pathological complete response. The purpose of this study was
      to investigate whether patients with residual DCIS only have the same prognosis
      as those with no residual invasive or in situ disease. A retrospective analysis
      of a prospectively maintained database identified 435 patients, who received
      neoadjuvant chemotherapy for operable breast cancer between February 1985 and
      February 2003. Of these, 30 (7%; 95% CI 5-9%) had no residual invasive disease or
      DCIS and 20 (5%; CI 3-7%) had residual DCIS only. With a median follow-up of 61
      months, there was no statistical difference in disease-free survival, 80% (95% CI
      60-90%) in those with no residual invasive or in situ disease and 61% (95% CI 35
      80%) in those with DCIS only (P=0.4). No significant difference in 5-year overall
      survival was observed, 93% (95% CI 75-98%) in those with no residual invasive or
      in situ disease and 82% (95% CI 52-94%) in those with DCIS only (P=0.3). Due to
      the small number of patients and limited number of events in each group, it is
      not possible to draw definitive conclusions from this study. Further analyses of
      other databases are required to confirm our finding of no difference in disease
      free and overall survival between patients with residual DCIS and those with no
      invasive or in situ disease following neoadjuvant chemotherapy for breast cancer.

PMID- 16421591
TI  - Increased risk of venous thromboembolism in patients with acute leukaemia.
AB  - Patients with malignancies have an increased risk for venous thromboembolisms
      (VTE), but data on patients with acute leukaemia are very limited so far. We
      found VTE in 12% of 455 patients with acute leukaemia, half of which occurred in
      association with central venous catheters, with equal risk of ALL and AML.

PMID- 16421592
TI  - COX inhibitors and breast cancer.
AB  - There is considerable evidence to suggest that prostaglandins play an important
      role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX)
      catalyses the conversion of arachidonic acid to prostaglandins. In recent years,
      there has been interest in a possible role for COX inhibitors in the prevention
      and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in
      several epithelial tumours, including breast cancer. Preclinical evidence favours
      an antitumour role for COX inhibitors in breast cancer. However, the
      epidemiological evidence for an association is conflicting. Trials are being
      conducted to study the use of COX inhibitors alone and in combination with other
      agents in the chemoprevention of breast cancer, and in the neo-adjuvant,
      adjuvant, and metastatic treatment settings. In evaluating the potential use of
      these agents particularly in cancer chemoprophylaxis, the safety profile is as
      important as their efficacy. Concern over the cardiovascular safety of both
      selective and nonselective COX-inhibitors has recently been highlighted.

PMID- 16421593
TI  - DNA hypermethylation in the normal colonic mucosa of patients with colorectal
      cancer.
AB  - The CpG-island methylator phenotype (CIMP+) in colorectal cancer (CRC) is
      characterised by frequent hypermethylation of promoter regions in tumour
      suppressor genes. Low level methylation of some CpG islands is also seen in the
      normal colonic mucosa and increases with age; however, it is still unclear what
      other factors regulate this phenomenon. The first aim of our study was to
      determine whether the level of promoter methylation is elevated in the normal
      colonic mucosa of patients with CIMP+ tumours. The second aim was to investigate
      whether common, functional polymorphisms in genes involved in methyl group
      metabolism are associated with the level of methylation in this tissue. CpG
      islands within the ERalpha, MYOD, P16(INK4A), MLH1, APC, P14(ARF), DAPK and TIMP3
      genes were quantitatively evaluated for methylation in normal colonic mucosa from
      a large series of CRC patients using the MethyLight assay. Genotyping was carried
      out for polymorphisms in the MTHFR, TS, MS, MTHFD1 and DNMT3b genes. Methylation
      of ERalpha and MYOD in normal colonic mucosa increased with age and was higher in
      female subjects. Methylation of P16(INK4A), MLH1, TIMP3 and DAPK in normal mucosa
      occurred at a lower level than ERalpha and MYOD but also increased with age and
      was significantly higher in patients with CIMP+ tumours. The DNMT3b C46359T
      polymorphism was associated with significantly less methylation of MYOD and MLH1
      and with trends for lower methylation in each of the other CpG islands examined.
      Our results demonstrate that age, gender and genetic factors can influence the
      methylation level of CpG islands in gene promoter regions of normal colonic
      mucosa. Further work is required to determine whether such methylation is
      associated with the development of CIMP+ CRC.

PMID- 16421594
TI  - Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable
      prognostic factor in non-small-cell lung carcinoma.
AB  - The purpose of this study was to clarify the relationship between the number of
      tumour-infiltrating T lymphocytes and the clinicopathological features and
      clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue
      specimens from 109 patients who underwent surgical resection for NSCLC were
      immunohistochemically analysed for CD4 and CD8 expression. Patients were
      classified into two groups according to whether their tumours exhibited a 'high'
      or 'low' level of CD8(+) or CD4(+) lymphocyte infiltration. Although the level of
      infiltration by CD8(+) T cells alone had no prognostic significance, the survival
      rate for patients with both 'high' CD8(+) and 'high' CD4(+) T-cell infiltration
      was significantly higher than that for the other groups (log-rank test, P=0.006).
      Multivariate analysis indicated that concomitant high CD8(+) and high CD4(+) T
      cell infiltration was an independent favourable prognostic factor (P=0.0092). In
      conclusion, the presence of high levels of both CD8(+) T cells and CD4(+) T cells
      is a significant indicator of a better prognosis for patients with NSCLC, and
      cooperation between these cell populations may allow a significantly more potent
      antitumour response than either population alone.

PMID- 16421595
TI  - Gene expression profiling of primary cultures of ovarian epithelial cells
      identifies novel molecular classifiers of ovarian cancer.
AB  - In order to elucidate the biological variance between normal ovarian surface
      epithelial (NOSE) and epithelial ovarian cancer (EOC) cells, and to build a
      molecular classifier to discover new markers distinguishing these cells, we
      analysed gene expression patterns of 65 primary cultures of these tissues by
      oligonucleotide microarray. Unsupervised clustering highlights three subgroups of
      tumours: low malignant potential tumours, invasive solid tumours and tumour cells
      derived from ascites. We selected 18 genes with expression profiles that enable
      the distinction of NOSE from these three groups of EOC with 92% accuracy.
      Validation using an independent published data set derived from tissues or
      primary cultures confirmed a high accuracy (87-96%). The distinctive expression
      pattern of a subset of genes was validated by quantitative reverse transcription
      PCR. An ovarian-specific tissue array representing tissues from NOSE and EOC
      samples of various subtypes and grades was used to further assess the protein
      expression patterns of two differentially expressed genes (Msln and BMP-2) by
      immunohistochemistry. This study highlights the relevance of using primary
      cultures of epithelial ovarian cells as a model system for gene profiling studies
      and demonstrates that the statistical analysis of gene expression profiling is a
      useful approach for selecting novel molecular tumour markers.

PMID- 16421596
TI  - Survivin expression in in situ and invasive breast cancer relates to COX-2
      expression and DCIS recurrence.
AB  - In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise
      survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking
      activated caspases. COX-2 expression limits the ubiquitination of survivin,
      protecting it from degradation. To determine if COX-2 expression in breast cancer
      showed an association with survivin expression, we assessed the levels of each
      protein in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC);
      relating expression patterns to recurrence of DCIS after surgery. Patterns of COX
      2 and survivin expression were determined by intensity-graded
      immunohistochemistry of the primary tumours. Patients with DCIS (n=161) which had
      either recurred (n=47) or shown no evidence of recurrence (n=114) 5 years
      following primary surgery were studied. These were compared to 58 cases of IBC.
      Survivin was expressed in the cytoplasm of 59% of DCIS and 17% of IBC. High
      levels of both cytoplasmic survivin and COX-2 expression significantly correlated
      to DCIS recurrence. COX-2 expression was present in 72% of DCIS, and levels of
      expression positively correlated with cytoplasmic survivin expression in DCIS and
      invasive disease. The majority of DCIS that recurred expressed both proteins
      (69%) vs 39% nonrecurrent. Recurrence was not seen in DCIS lacking both proteins
      at 5 years (P=0.001). Expression of the IAP survivin is increased in DCIS and
      correlates closely with COX-2 expression. Increased expression of IAP, (leading
      to reduced apoptosis) may explain the effect of COX-2 in increasing recurrence of
      DCIS after surgical treatment.

PMID- 16421597
TI  - COSMIC 2005.
AB  - The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was
      developed to preserve somatic mutation data and share it with the community. Over
      the past 25 years, approximately 350 cancer genes have been identified, of which
      311 are somatically mutated. COSMIC has been expanded and now holds data
      previously reported in the scientific literature for 28 known cancer genes. In
      addition, there is data from the systematic sequencing of 518 protein kinase
      genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency
      above 5% in one or more tumour type, no mutations were found in 333 genes and 180
      are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site
      has been expanded to give more views and summaries of the data and provide faster
      query routes and downloads. In addition, there is a new section describing
      mutations found through a screen of known cancer genes in 728 cancer cell lines
      including the NCI-60 set of cancer cell lines.

PMID- 16421598
TI  - A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to
      severe sepsis in the Spanish population.
AB  - Sepsis describes a complex clinical syndrome resulting from a systemic
      inflammatory response to bacteria. Functional studies in animal models of sepsis
      have catalogued CXCL2 as a candidate gene for the development of the disease. We
      hypothesized that CXCL2 polymorphisms may confer susceptibility to sepsis and
      performed an association study using 178 severe sepsis patients and 357
      population-based controls. We selected two polymorphisms from the promoter of the
      gene (-437A/G and -665(AC)n), and analyzed whether haplotypes or single loci were
      associated with disease susceptibility. An overall test of differentiation showed
      that haplotype distribution was not different between cases and controls
      (P=0.407). Likewise, -437A/G was not associated with disease susceptibility
      (heterozygote odds ratio (OR) 0.68 (0.47-1.03), and homozygote OR 0.86 (0.56
      1.32); P=0.706). However, for the -665(AC)n, we found that the 24+/-1 repeat
      alleles were associated with susceptibility (heterozygote OR 2.82 (1.10-7.24),
      and homozygote OR 3.65 (1.41-9.43); P=0.0006). This association remained
      significant when using a multiple logistic regression analysis (OR 2.23; 95%
      confidence intervals (95% CI) 1.22-4.03; P=0.008) and after a genomic control
      adjustment (P=0.017). Although replicate studies and functional assays are
      needed, these results suggest that CXCL2 gene variants may contribute to the
      development of severe sepsis.

PMID- 16421600
TI  - Genetic design of an optimized packaging cell line for gene vectors transducing
      human B cells.
AB  - Viral gene vectors often rely on packaging cell lines, which provide the
      necessary factors in trans for the formation of virus-like particles. Previously,
      we reported on a first-generation packaging cell line for gene vectors, which are
      based on the B-lymphotropic Epstein-Barr virus (EBV), a human gamma-herpesvirus.
      This 293HEK-derived packaging cell line harbors a helper virus genome with a
      genetic modification that prevents the release of helper virions, but efficiently
      packages vector plasmids into virus-like particles with transducing capacity for
      human B cells. Here, we extended this basic approach towards a non-transforming,
      virus-free packaging cell line, which harbors an EBV helper virus genome with
      seven genetic alterations. In addition, we constructed a novel gene vector
      plasmid, which is devoid of a prokaryotic antibiotic resistance gene, and thus
      more suitable for in vivo applications in human gene therapy. We demonstrate in
      this paper that EBV-based gene vectors can be efficiently generated with this
      much-improved packaging cell line to provide helper virus-free gene vector stocks
      with transducing capacity for established human B-cell lines and primary B cells.

PMID- 16421599
TI  - Development of a rapid method to generate multiple oncolytic HSV vectors and
      their in vivo evaluation using syngeneic mouse tumor models.
AB  - Replication-conditional herpes simplex virus (HSV)-based vectors have great
      potential in the treatment of various types of cancers including brain tumors.
      HSV mutants lacking the U(L)39 gene and both copies of the gamma(1)34.5 gene
      (e.g. MGH1, G207) have been demonstrated to possess oncolytic effects as well as
      potent anticancer vaccination effects without compromising safety. Such mutants
      thus provide optimal templates to produce novel oncolytic HSV vectors for cancer
      gene therapy applications. In order to accomplish quick and efficient
      construction of oncolytic HSV vectors, a novel BAC-based method designated as
      'HSVQuik system' was developed. This system sequentially utilizes two different
      site-specific recombination systems to introduce virtually any transgene
      cassettes of interest into the deleted U(L)39 locus (Flp-FRT in Escherichia coli)
      and to release the vector genome sequence from the procaryotic plasmid backbone
      (Cre-loxP in Vero cells). Taking advantage of the HSVQuik system, we constructed
      three oncolytic HSV vectors that express mouse IL4, CD40 ligand and 6CK,
      respectively. In vivo therapeutic experiments using two luciferase-labeled
      syngeneic mouse brain tumor models revealed that expression of these
      immunomodulators significantly enhanced antitumor efficacy of oncolytic HSV. The
      HSVQuik system, together with luciferase-labeled tumor models, should expedite
      the process of generating and evaluating oncolytic HSV vectors for cancer gene
      therapy applications.

PMID- 16421601
TI  - The CD20/alphaCD20 'suicide' system: novel vectors with improved safety and
      expression profiles and efficient elimination of CD20-transgenic T cells.
AB  - Adoptive transfer of T lymphocytes is an attractive strategy for many
      experimental treatment strategies for cancer. Unfortunately, manipulated T cells
      could be responsible for serious adverse events. Retroviral CD20-transduced T
      cells may be able to control these unwanted effects. CD20-positive cells are
      sensitive to rituximab (RTX), a monoclonal antibody specific for CD20. This
      permits their selective elimination in vivo in case of adverse events. To this
      end, a system is required that permits efficient and safe transduction of donor T
      cells and effective elimination of CD20-positive T cells. We constructed
      different CD20-encoding retroviral vectors and investigated the impact of
      inclusion of the woodchuck post-transcriptional regulatory element (WPRE) and the
      chicken hypersensitivity site 4 insulator elements on the levels, homogeneity and
      stability of CD20 expression. Importantly, inclusion of either WPRE or insulator
      elements in the retroviral vector resulted in a dramatic improvement in the
      stability of CD20 expression. The insulator element also led to a much more
      homogeneous level of CD20 expression. We also show the efficient elimination of
      the CD20-transgenic T cells via RTX by different effector mechanisms. In
      conclusion, we have constructed CD20-encoding retroviral vectors with improved
      efficiency and safety profiles, which can be used as a suicide strategy.

PMID- 16421602
TI  - Etiological factors of unconsummated marriage.
AB  - Normal erectile function is subjected to the influence of psychological,
      hormonal, neurological, vascular and cavernosal factors. Unconsummated marriage
      is a common medical and social problem in andrology clinics in conservative
      communities. However, its etiological factors remain unclear. This work aimed to
      define the probable etiology of unconsummated marriage. A total of 191 patients
      were evaluated through history taking, constructed questionnaire, educational
      settings, clinical examination, lab investigation, imaging procedures and other
      measures. Psychogenic factors were the cause in 74.4% of the investigated
      patients. Performance anxiety was the cause in 52.9%, and in 21.5% other
      psychological distresses were responsible. Organic causes represent 7.3%,
      vaginismus 8.4%, premature ejaculation 3.1% and cases with undetermined etiology
      were 6.8%. In conclusion, performance anxiety was revealed to be the main
      contributor. However, other psychogenic, organic and social factors represent
      sizable etiological factors.

PMID- 16421603
TI  - The future of sexual medicine for the urologist.
AB  - Editor's note: Winston Churchill said, 'I never worry about action, but only
      inaction'. Experience has taught the medical profession that action, change and
      adaptation are the rule as novel technologies and therapies are introduced into
      the mainstream of medical care. Sexual medicine is no exception. Originally
      thought to be psychogenic in origin, it is now well accepted that erectile
      dysfunction (ED) is predominately organic in origin in most middle-aged men.
      Treatment of organic ED has evolved with the introduction of novel, oral
      therapies, such as phosphodiesterase inhibitors. Adaptation has also led to
      incorporation of ED into the treatment realm of the primary-care physician. As
      sexual medicine becomes increasingly non-surgical, the challenge to the surgical
      specialists will reside in their ability to change and adapt to this ever
      burgeoning medical discipline. Lawrence Ross, President-Elect of the American
      Urological Association, discusses action and change below. If urologists are to
      remain involved in sexual medicine, then his action plan must be brought to
      fruition.

PMID- 16421606
TI  - Epigenetics: sins of the fathers, and their fathers.

PMID- 16421604
TI  - PTEN and GSK3beta: key regulators of progression to androgen-independent prostate
      cancer.
AB  - Prostate cancer (PrCa) is characterized by progression from an androgen-dependent
      phenotype to one that is inevitably androgen independent (AI) and lethal. Recent
      evidence strongly suggests that the phosphatidylinositol-3-kinase/Akt (PI3K/Akt)
      and androgen receptor (AR) signalling pathways provide prostatic epithelium with
      the necessary signalling events to escape the apoptotic response associated with
      androgen withdrawal therapy. Silencing of phosphatase and tensin homologue
      deleted on chromosome 10 (PTEN) and glycogen synthase kinase beta (GSK3beta) are
      frequently associated with advanced PrCa systems and likely serve critical roles
      in promoting AR and PI3K/Akt gain-of-function. That PTEN negatively regulates AR
      and is sufficient to promote metastatic PrCa in murine models strongly implies
      its role as a gatekeeper of progressive PrCa. In human PrCa, PTEN loss is
      correlated with substantial increases in Akt(Ser473) and integrin-linked kinase
      expression, both of which promote Ser(9) phospho-inhibition of GSK3beta and
      inactivation of apoptotic factors. Sufficient evidence also suggests that
      GSK3beta is not only a critical regulator of proproliferative signalling but also
      a promiscuous one as PI3K/Akt pools of GSK3beta are, at least in part,
      functionally interchangeable with those of the Wnt/beta-catenin pathway. Thus,
      GSK3beta may serve not only as a mediator of PI3K/Akt activation but may also
      regulate the potent transactivation and proproliferative effects that Wnt3a and
      beta-catenin confer upon AR. These data suggest that prostate-specific activation
      of GSK3beta may serve as a viable pharmacological option. Thus, in this review,
      we emphasize that temporal changes in GSK3beta and PTEN expression during
      progression to AI PrCa are important factors when considering the potential for
      therapies targeting the oncogenic contributions of PI3K/Akt and AR signalling
      pathways.

PMID- 16421608
TI  - [Health care in catastrophes].

PMID- 16421609
TI  - [Telemedicine: science or fiction?].
AB  - Telemedicine has been considered to be a scientific discipline midway between
      medicine and technology. Thus, over the last decade it has been largely
      influenced by the continuous development of computer and communications
      technologies. Now that the phase of its laboratory investigation has been
      completed, it can be considered to be a technique in a mature state. Hence, both
      from the point of view of technology suppliers and of the users of medicine 
      patients and professionals- there is a demand for a takeoff in the arena of its
      implantation, that is to say, the need for new health services based on
      telemedicine. This article offers an up-to-date view of the state of the art of
      telemedicine but without entering into an in-depth evaluation and description of
      the technology and its applications. On the contrary, our aim is to make it known
      to users and to the different health organisations, including their managers,
      that the conditions for its development are now available. Thus the success or
      failure of its implantation is a task for all of the actors involved. What is
      certain is that in the light of the experience and results of its application
      during the last decade, both in our surrounding geographical milieu and in the
      United States, there are unmistakable signs that telemedicine is here to stay.

PMID- 16421610
TI  - [Stroke risk factors. Population case-control study in the Foral Community of
      Navarre].
AB  - BACKGROUND: To determine the prevalence of different risk factors in patients
      with cerebrovascular disease of a population in the Foral Community of Navarre,
      and to compare this with a control group with the same characteristics. PATIENTS
      AND METHODS: Population-based case-control study of a basic health zone (12,200
      inhabitants). We included 91 patients, diagnosed with the first episode of
      cerebrovascular disease (1999-2003), and 182 controls (2 per case), paired by age
      and sex in the same time period. RESULTS: The estimation of the incidence of
      cerebrovascular disease in our series is between 160 and 190 cases/100,000
      inhabitants and year. The prevalence of arterial hypertension in the
      cerebrovascular disease group is 75%; 25% have previously suffered a transient
      ischemic attack and 31% had atrial fibrillation. Other vascular risk factors such
      as diabetes or hyperlipidaemia are present in 33% and 38%, respectively. Other
      risk factors are smoking (25%), ischemic cardiopathy (14%) and family antecedents
      of cerebrovascular disease (21.3%). An association has been found between
      cerebrovascular disease and arterial hypertension (OR=2.2; 95% CI = 1.2-4.0),
      personal antecedent of transient ischemic attack (OR=4.0; 95% CI 1.9-8.5), atrial
      fibrillation (OR=2.8; 95% CI 1.4-5.3), diabetes mellitus (OR=2.5; 95% CI 1.3-4
      6). CONCLUSIONS: The results obtained on a population basis - not only a hospital
      basis - will help us to obtain a more precise understanding of the aetiopathogeny
      of cerebrovascular disease. The results observed for arterial hypertension,
      diabetes mellitus and hyperlipidaemia, since they are modifiable risk factors;
      underline the importance of primary prevention. Similarly, such measures should
      be strengthened in the subjects with atrial fibrillation. The association with
      prior diagnosis of transient ischemic attack strengthens the need for adjusting
      the secondary prevention measures in this group of patients.

PMID- 16421611
TI  - [Cohort of asbestos exposed workers. Navarre (Spain) 1999-2004].
AB  - BACKGROUND: The identification of a population cohort of workers exposed to
      asbestos is important because it facilitates health surveillance, allowing us to
      fulfil the ethical obligation of recognizing the occupational origin of the
      illness and contributing to the development of scientific research. The goal of
      this study is to identify the asbestos exposed workers in Navarre and the success
      of the health surveillance offer. METHODS: The register of asbestos exposed
      workers was created in 1999. It includes companies and workers from the national
      register, the records of the regional institution of occupational health and the
      data of the occupational health services and the inspectorate of sick leave. The
      health programme deals with occupational and post-occupational workers. RESULTS:
      The cohort consists of 2,294 workers, from 33 companies, 40% of whom are active,
      half work manufacturing motor vehicles, 91% are exposed to chrysotile, 25%
      exposed to high concentrations (0.20 fibers /cm3 or more for chrysotile or 0.10
      fibers /cm3 for others). The 1970s and 1990s were when most workers began to be
      exposed. Workers who began in the 1940s and 1950s have longer exposure times.
      Medical surveillance is accepted by 72%, with higher acceptance among those who
      are active. CONCLUSIONS: The follow-up has allowed us to recognize three times as
      many cases of pathology for asbestos, in comparison with those declared
      spontaneously in the eleven years prior to the program, which reflects its
      importance. The level of acceptance of the surveillance is adapted, given the
      methodology of the programme.

PMID- 16421612
TI  - [Non-invasive home mechanical ventilation in the COPD patient].
AB  - BACKGROUND: The potential benefits of non-invasive mechanical breathing in
      clinically stable COPD patients are still not well known, nor have they been
      sufficiently studied. We evaluate whether non-invasive mechanical ventilation is
      beneficial to these patients. METHODS: A cross sectional study was carried out
      evaluating the application of non-invasive home mechanical ventilation (BIPAP),
      during the nocturnal rest in 23 COPD patients, who presented hypercapnia in basal
      arterial gasometry during clinical stability. Clinical, gasometric and
      spirometric evaluations were carried out 3, 6 and 12 months after initiating this
      therapy. Similarly, an evaluation was made of the number of admissions due to
      worsening of the underlying respiratory pathology during one year. Results. The
      patients included in the study had an average age of 68.83 years. Sixty point
      nine percent (60.9%) presented a severe degree of COPD. Sixty-nine point six
      percent (69.6%) of the total sample had previously received continuous
      oxygenotherapy at home; 75% of them presented severe or very severe COPD. During
      the period of time of the study a fall was recorded in the number of hospital
      admissions due to worsening (0.61+/-0.15 annual admissions on average) with
      respect to the period of time prior to the non-invasive mechanical ventilation
      (1.07+/-0.16 admissions on average), with greater benefits obtained by those who
      had previously shown a higher number of admissions and those with associated
      comorbidity. A reduction was also appreciated in the arterial pressure of carbon
      dioxide (PaCO2) in the majority of cases, principally those who at the start of
      the study presented a PaCO2>63.32 mm of Hg; this improvement was appreciated from
      the first three months of treatment.

PMID- 16421613
TI  - [Evaluation of the MTD-2 test for the direct detection of Mycobacterium
      tuberculosis in specimens].
AB  - BACKGROUND: To evaluate the utility of the Amplified Mycobacterium Tuberculosis
      Direct Test (MTD-2, Gen-Probe) in the microbiological diagnosis of tuberculosis.
      METHODS: We evaluated the results obtained in 146 specimens with the MTD-2 test,
      together with those of the culture and smears. The MTD-2 test was performed on
      all the smear positives specimens (n=47), on the smear-negative specimens, when
      the test was demanded (n=19), and in other smear-negative specimens previously
      selected, according to the clinical history of the patient (n=80). We considered
      real cases of tuberculosis, those that were culture positive for Mycobacterium
      tuberculosis and those that were specifically treated. RESULTS: The overall
      sensitivity, specificity, positive and negative predictive values for the MTD
      test were: 95, 76, 71, and 96%, for the culture; and 84, 100, 100 and 90% and 75,
      94, 89 and 86% for the smears, respectively. In smear positive specimens, the
      test showed a great specificity, and differentiated M. tuberculosis from other
      mycobacteria. In the smear negatives, the sensitivity of the test was low and so
      was the positive predictive value, especially in series performed with a high
      work load. CONCLUSIONS: Data from our study show that the MTD-2 test is a
      reliable method for rapid diagnosis of tuberculosis in smear positive specimens.
      However, due to its low sensitivity and positive predictive value, it is not
      recommended in the routine diagnosis of tuberculosis. Also, for this reason,
      whenever a positive result is obtained with a smear negative specimen, the result
      needs to be confirmed with another specimen.

PMID- 16421614
TI  - [Role of IL-6 and its -174G>C polymorphism in weight management and in the
      metabolic comorbidities associated with obesity].
AB  - Obesity and its comorbidities have been associated with a low grade
      proinflammatory state, in which the adipose tissue seems to be involved. In fact,
      this tissue produces different proinflammatory cytokines, such as IL-6 and
      others. High circulating concentrations of IL-6 have been related to high body
      mass index, to diabetes mellitus type 2, to lipid abnormalities and to high blood
      pressure. There are some studies, which reported a relationship between IL-6 and
      energy metabolism, so this cytokine and its -174G>C gene polymorphism could be
      factors involved in the development of obesity. Different studies have associated
      the G allele of the IL-6 gene with obesity, with insulin resistance and with
      different cardiovascular risk factors. However, other published reports have
      associated the C allele of this gene to these metabolic disturbances and
      pathologies. This paper reviews recently published evidences about IL-6 and its
      physiopathological involvement in obesity and comorbidities, with emphasis on the
      role of the -174G>C polymorphism in the aetiology of these disturbances, in which
      obesity is a major risk factor.

PMID- 16421615
TI  - [Primary CNS Lymphoma: bibliographical review and experience at the Hospital of
      Navarre in the last 5 years (2000-2004)].
AB  - Primary cerebral lymphoma (Primary CNS Lymphoma, PCNSL) is an aggressive non
      Hodgkin lymphoma that originates in the central nervous system without evidence
      of lymphoma in any other localization at the time of diagnosis. Primary cerebral
      lymphomas are less well-known and are characterized than their homologues the
      systemic lymphomas, as they are an entity whose frequency was scarce until a few
      decades ago. However, the great rise in incidence that this pathology has
      undergone over the last three decades, and which is still unexplained, makes more
      studies necessary to better understand the etiopathology of this entity. Thanks
      to the new systems of treatment, the prognosis of this pathology has improved
      significantly in recent years. Nonetheless, treatment of primary cerebral
      lymphoma continues to give rise to numerous controversies at present due to its
      high neurotoxicity in patients over 60 years of age, a group of patients
      frequently affected by this pathology. To resolve these and other questions it is
      necessary to deep in the study of primary cerebral lymphoma and to carry out high
      quality clinical trials.

PMID- 16421616
TI  - [Satisfaction of patients with cervical pain and low back pain in a
      rehabilitation service].
AB  - BACKGROUND: The aims of the present paper are: to reduce waiting time for
      treatment of patients with low back pain/cervical pain; to determine the degree
      of satisfaction of patients being treated by groups; and to determine whether
      there is correlation amongst satisfaction, improvement of pain and impact on the
      activities of everyday life. METHODS: Prospective observational study. STUDY
      POPULATION: users of the surgeries of a tertiary hospital and the specialties
      center attached to it, who attended surgery because of cervical/low back pain,
      and practiced a serie of exercises. PERIOD OF STUDY: 1 october 2001 to 1 April
      2002. The instrument of measurement used for evaluating pain and disability was
      the Von Korff questionnaire for low back pain, with an adaptation of this
      questionnaire for cervical pain. STATISTICAL ANALYSIS: Wilcoxon's non-parametric
      test. RESULTS: Total number of patients 273 (176 with cervical pain and 97 with
      low back pain): 198 women and 75 men. Average age: 48.5 (20-81). The self
      perceived evaluation of the patients treated in a group improved in 72 subjects
      (p<0.0001) with cervical pain and in 33 (p<0.001) with low back pain. Post
      treatment pain was significantly better (p<0.001) than pre-treatment pain in both
      groups. Its influence on the activities of everyday life did not achieve
      statistical significance. Perception of the information received was positive in
      the cervical group (p<0.05). CONCLUSIONS: Following the application of different
      techniques: reduction in number of patients and waiting time - decisive factors
      in the satisfaction of these patients; a good acceptance of group treatment was
      obtained, ameliorating pain. The degree of knowledge of their pathology only
      improved in the cervical group.

PMID- 16421617
TI  - [Effect of birth cohort, period of diagnosis and age on cancer incidence in
      Navarra, 1973-1997].
AB  - BACKGROUND: Population-based registers are one source of information about cancer
      incidence. Systematic study of its incidence in a specific population is a
      fundamental tool for estimating the present-day and future magnitude of cancer
      and provides elements for taking decisions with regard to the allocation of
      health resources. The aim of this article was to investigate the time trend in
      the incidence pattern of cancer in Navarre during the period 1973-1997, and to
      identify the components of age, diagnosis period and birth cohort as determinants
      of the time trend of cancer incidence. METHODS: Descriptive study of cancer
      incidence through age-period-cohort models. Monitoring of dynamic cohort over 25
      years. Classical incidence summarizing indicators were analysed. Log-linear
      Poisson models were developed to quantify cancer risk and the relative annual
      trend. Age-period-cohort models were adjusted in order to ascertain the effect on
      the time trend exerted by the respective age, diagnosis period and birth cohort
      components. RESULTS: The age-standardized rate incidence for all sites -except
      non melanoma skin tumours- is maximum in the five-year period 1993-1997, in men:
      304,1 new cases per 100,000 person-years, and in women: 190,6 new cases per
      100,000 person-years. The average incidence changes for each of the 25 years of
      monitoring of the set data studied is 1.88% (95% CI 1.69 to 2.07) in men and
      1.32% (95% CI 1.09 to 1.54) in women. The cancer increase in women is more
      pronounced from 35 to 64 years, a fact which should alert health authorities
      about the future evolution of cancer incidence in women. In the analysis of the
      trend components sharp increases are observed for the consecutive generations of
      males born in Navarre since 1900. In women, the risk associated with the year of
      birth increases markedly in the generations born after 1930-1940. CONCLUSIONS:
      There was an important increase in cancer incidence in Navarre from 1973 to 1997,
      in men and women. The cancer incidence pattern in Navarre does not yet show signs
      of stabilization.

PMID- 16421618
TI  - [Reasons to advise against temporary henna tattoos].

PMID- 16421619
TI  - [Comments on the paper: pronostic value of the reception, attendance and
      classification of patients in the emergency department of a tertiary hospital].

PMID- 16421621
TI  - [Septic thrombophlebitis of the portal vein (pylephlebitis): diagnosis and
      management of three cases].
AB  - BACKGROUND: Pylephlebitis is thrombophlebitis of the portal vein and/or of its
      branches; it is acute and generally arises as a complication of inflammatory
      intra-abdominal processes or of surgical interventions in patients with blood
      discrasies. As its clinical picture is fairly non-specific, radiological
      findings, while not pathognomonic, are of great use in early diagnosis and
      improved vital prognosis of these patients. The aims of this study are to review
      the pathophysiology of this entity and its clinical and radiological
      presentation, which allow for early clinical suspicion. CLINICAL CASES: Three
      cases of pylephlebitis are presented, two of them post-surgical, in which the
      only common clinical data for suspicion were the febricula and leucocytosis.
      Diagnosis was obtained from the finding of helicoidal computer tomography with IV
      contrast - Somaton Siemens - and abdominal echography - Ellegra Siemens - carried
      out on the three. The result of these tests was decisive for an early diagnosis,
      efficient treatment and satisfactory evolution in the three cases. DISCUSSION: We
      wish to emphasize the importance of clinical suspicion and early radiology for an
      early diagnosis of this entity, which make it possible to establish an efficient
      treatment.

PMID- 16421620
TI  - [Osteoporosis management in primary care].

PMID- 16421622
TI  - [Bilateral chylothorax after gastric surgery].
AB  - Chylothorax is a lymphatic effusion of chylous in the pleural space due to
      thoracic duct obstruction or injury. The most frequent aetiology is cancer; it is
      also related to chest trauma and iatrogenic. We describe the case of bilateral
      chylothorax in a 76-year-old woman, right predominant, during the post
      operational phase of gastric surgery. This presented itself with respiratory
      insufficiency and tachycardia without initial haemodynamic compromise. It
      presented a favourable evolution after conservative treatment, cessation of oral
      intake and TPN and chest tube during 10 to 14 days.

PMID- 16421623
TI  - Polysaccharides from the root of Angelica sinensis protect bone marrow and
      gastrointestinal tissues against the cytotoxicity of cyclophosphamide in mice.
AB  - Cyclophosphamide (CY) is a cytostatic agent that produces systemic toxicity
      especially on cells with high proliferative capacity, while polysaccharides from
      Angelica sinensis (AP) have been shown to increase the turnover of
      gastrointestinal mucosal and hemopoietic stem cells. It is not known whether AP
      has an effect on CY-induced cytotoxicity on bone marrow and gastrointestinal
      tract. In this study, we assessed the protective actions of AP on CY-induced
      leukopenia and proliferative arrest in the gastroduodenal mucosa in mice.
      Subcutaneous injection of CY (200 mg/kg) provoked dramatic decrease in white
      blood cell (WBC) count and number of blood vessels and proliferating cells in
      both the gastric and duodenal mucosae. Subcutaneous injection of AP significantly
      promoted the recovery from leukopenia and increased number of blood vessels and
      proliferating cells in both the gastric and duodenal tissues. Western blotting
      revealed that CY significantly down-regulated the protein expression of vascular
      endothelial growth factor (VEGF), c-Myc and ornithine decarboxylase (ODC) in
      gastric mucosae but had no effect on epidermal growth factor (EGF) expression. AP
      also reversed the dampening effect of CY on VEGF expression in the gastric
      mucosa. These data suggest that AP is a cytoprotective agent which can protect
      against the cytotoxicity of CY on hematopoietic and gastrointestinal tissues when
      the polysaccharide is co-administered with CY in cancer patients during treatment
      regimen.

PMID- 16421624
TI  - Effect of antibodies on the expression of Plasmodium falciparum circumsporozoite
      protein gene.
AB  - Antibodies are known to play an important role in the control of malaria
      infection. However, they can modulate parasite development enhancing infection.
      The effect of anti-Plasmodium antibodies on the expression of circumsporozoite
      protein gene (csp) was investigated. Plasmodium falciparum 3D7 in vitro cultures
      were submitted to: i) anti- circumsporozoite protein monoclonal antibody (anti
      CSP-mAb) [1microg/ml, 0.1microg/ml, 0.01microg/ml and 0.001microg/ml] and ii)
      purified IgG Fab fragment from a pool of malaria patients [1mg/ml and
      1microg/ml]; and compared to control cultures. After 24h the number of ring
      infected erythrocytes was determined in order to calculate invasion efficacy. At
      48h culture supernatant was collected, and the amount of circumsporozoite protein
      determined by ELISA, parasitaemia was calculated and cells were processed for RNA
      preparation. Expression of csp gene was quantified using Real time RT-PCR. There
      was an increase in parasite growth when treated with lower anti-CSP-mAb
      concentration, which was associated with lower csp expression, while 1mug/ml anti
      CSP-mAb treatment presented a growth inhibitory effect accompanied by high csp
      expression.

PMID- 16421625
TI  - Postoperative pain scores and analgesic requirements after thyroid surgery:
      comparison of three intraoperative opioid regimens.
AB  - PURPOSE: This study was designed to compare the effect on postoperative pain,
      opioid consumption and the length of stay in postoperative care unit (PACU) after
      three different intraoperative analgesic regimens in thyroid surgery. METHODS:
      Seventy five patients were enrolled into the study and assigned to one of three
      groups, fentanyl, sufentanil or remifentanil (n=25 for each group). Before the
      end of surgery, paracetamol 1 gr and nefopam 20 mg was also administered in all
      patients. Pain scores, opioid demand and the length of stay in PACU were assessed
      in a blind manner. RESULTS: Post operative pain scores were significantly lower
      in the fentanyl and sufentanil groups compared to remifentanil group (55 +/- 15,
      and 60 +/- 10 versus 78+/- 12, P < 0.05). Patients in the remifentanil group
      stayed longer in the PACU 108+/- 37 min versus 78+/-31 and 73 +/- 25 min, (P<
      0.05). CONCLUSION: After remifentanil based analgesia, anticipation of
      postoperative pain with opioid analgesic appears mandatory even for surgery rated
      as being moderately painful, otherwise longer opioid titration due to higher pain
      scores might delay discharge time.

PMID- 16421626
TI  - Correlations of HBV genotypes, mutations affecting HBeAg expression and HBeAg/
      anti-HBe status in HBV carriers.
AB  - This study was carried out to determine the effects of hepatitis B virus
      genotypes, core promoter mutations (A1762G1764-->T1762A1764) as well as precore
      stop codon mutations (TGG-->TAG) on HBeAg expression and HBeAg/ anti-HBe status.
      Study was also performed on the effects of codon 15 variants (C1858/ T1858) on
      the predisposition of precore stop codon mutations (TGG-->TAG). A total of 77
      sera samples were analyzed. Fifty one samples were successfully genotyped of
      which the predominant genotype was genotype B (29/ 51, 56.9 %), followed by
      genotype C (16/ 51, 31.4 %). Co-infections by genotypes B and C were observed in
      four samples (7.8 %). To a lesser degree, genotypes D and E (2.0 % each) were
      also observed. For core promoter mutations, the prevalence was 68.8 % (53/ 77)
      for A1762G1764 wild-type and 14.3 % (11/ 77) for T1762A1764 mutant while 9.1 %
      (7/ 77) was co-infected by both strains. The prevalence of codon 15 variants was
      found to be 42.9 % (33/ 77) for T1858 variant and 16.9 % (13/ 77) for C1858
      variant. No TAG mutation was found. In our study, no associations were found
      between genotypes (B and C) and core promoter mutations as well as codon 15
      variants. Also no correlation was observed between HBeAg/ anti-HBe status with
      genotypes (B and C) and core promoter mutations.

PMID- 16421627
TI  - Impact of clinically relevant progestins on the neural effects of estradiol and
      the signaling pathways involved.
AB  - The natural ovarian hormone progesterone functions as an effective
      neuroprotective agent. However, in its native state it is not an efficient
      therapeutic compound because of its poor bioavailability. Thus, for practical
      therapeutic usage it became necessary to develop orally active progestogens for
      use in hormone therapy. We have shown that not all progestogens are equal in
      their ability to modulate neuronal survival and markers of neuronal plasticity.
      Thus, one cannot assume that all hormone therapies will perform the same, and it
      is crucial to determine the neural effects and interactions with estradiol of
      synthetic progestins used in place of natural progesterone. We have analyzed a
      number of clinically relevant progestins for neuroprotective efficacy. These in
      vitro analyses of neuroprotective efficacy could serve as a predictive index of
      clinical efficacy for progestins to protect against degenerative insults that
      lead to Alzheimer's disease. To aid in such therapeutic development, we
      determined the chemical structural features that predict progestin efficacy in
      the brain and showed that binding affinity does not predict neuroprotective
      efficacy or the direction of effect and thus cannot be used as an indicator of
      neurological benefit. In contrast, there was a set of common features of ligand
      receptor interactions that are correlative and hopefully predictive of
      neuroprotective efficacy. Elucidation of the sites and targets of progestogen
      action should have a clear impact on both the use of hormone therapy for the
      prevention of neurodegenerative disease and the future design of target-specific
      hormone therapy formulations.

PMID- 16421628
TI  - The role of adult stem cells in carcinogenesis.
AB  - The role of adult stem cells in tissue regeneration has attracted much interest
      because of its enormous therapeutic potential. Adult stem cells reside in every
      tissue of the body and have the ability to self-renew and to give rise to a high
      number of differentiated progeny. These are indeed the essential steps in tissue
      regeneration, which in some cases occurs constitutively, whereas in other cases
      happens in response to an injury. The identification of the key factors involved
      in self-renewal and differentiation pathways is at the top of the agenda of stem
      cell biologists. Interestingly, a number of factors that govern the fate of adult
      stem cells also play a role in malignant cell transformation, such as the Wnt
      cascade, Oct-4, Bmi-1 and Evi1. In addition, rare subpopulations of cancer stem
      cells were identified for leukemia and other solid tumors. These rare fractions
      of cancer stem cells are in large part responsible for maintaining the tumor
      mass, as they have the capacity to self-renew and to generate a high number of
      progeny via differentiation program. These findings can be considered a major
      breakthrough in cancer research. Currently, oncologists and stem cell biologists
      have two main goals: i) the assessment of the consistency of the line that
      divides adult stem cells and carcinogenesis; ii) to better characterize the
      biology of cancer stem cells. This new line of investigation may allow for the
      development of novel therapeutics and cancer diagnostics.

PMID- 16421629
TI  - Role of central glutamatergic neurotransmission in the pathogenesis of
      psychiatric and behavioral disorders.
AB  - Glutamate is the most ubiquitous of the fast excitatory neurotransmitters in the
      central nervous system. In the process, glutamate fulfills numerous physiological
      functions, but also plays an important role in the pathophysiology of a variety
      of psychiatric and behavioral disorders such as schizophrenia. Recently,
      modulation of glutamatergic neurotransmission has been suggested to be involved
      in the mechanisms of action of antipsychotic drugs. Thus, pharmacological
      manipulation of glutamatergic transmission may be a feasible therapeutic strategy
      for treatment of schizophrenia. In this review article, we focus on the role of
      central glutamatergic neurotransmission in the pathogenesis and pharmacotherapy
      of schizophrenia and the development of new drugs targeting glutamate brain
      systems.

PMID- 16421630
TI  - Transcriptional control of pancreatic endocrine cell development.
AB  - In diabetes mellitus, insulin-producing beta cells in the pancreas are lost (type
      1) or dysfunctional (type 2). Cell replacement therapy has emerged as a promising
      alternative to insulin injection for treatment of diabetic patients. Given the
      scarcity and difficulty in obtaining pancreatic beta cells from cadaveric donors,
      current research is aiming at the generation of functional beta cells from non
      beta-cell sources or from pluripotent progenitors such as adult or embryonic stem
      cells. However, to achieve this, we first need to understand how beta cells are
      formed during normal development. Knowledge of the molecular and genetic pathways
      that direct cells along their differentiation pathway will be instrumental if we
      aim to engineer new beta cells for clinical use. This article reviews pancreatic
      development from a gene expression point of view and discusses our current
      understanding of the transcription factors that rule pancreatic morphogenesis
      during ontogeny.

PMID- 16421631
TI  - Molecule of the month. Rotigaptide.

PMID- 16421632
TI  - Highlights from the Fifth International Meeting on Metabotropic Glutamate
      Receptors, held September 18-23, 2005, in Taormina, Sicily, Italy. Metabotropic
      glutamate receptors as therapeutic targets.
AB  - The study of metabotropic glutamate receptors (mGluRs) is one of the fastest
      growing areas of neuropharmacology. The Fifth International Meeting on
      Metabotropic Glutamate Receptors, held September 18-23, 2005, in Taormina,
      Sicily, Italy, encompassed more than 80 oral presentations and 70 poster
      presentations. The role of mGluRs in various physiological and pathological
      conditions, such as learning and memory, modulation of sensory inputs, control of
      movement, schizophrenia, anxiety, seizures, addiction to drugs, neurodegeneration
      and developmental regulation of synaptic circuits, was discussed.

PMID- 16421633
TI  - Highlights from the First International Conference in Vascular Medicine, held
      August 26-28, 2005, in Melbourne, Australia. Vascular medicine in Australia and
      Germany.
AB  - Recent developments highlighted from the First International Conference in
      Vascular Medicine, held in Melbourne, Australia, August 26-28, 2005, are in
      nitric oxide signaling, oxidative stress, homeostasis, the angiotensin
      aldosterone system, diabetes, new vessel formation and P-selectin.

PMID- 16421634
TI  - Molecular characterization of the first Aichi viruses isolated in Europe and in
      South America.
AB  - The occurrence of Aichi virus, a picornavirus associated with acute
      gastroenteritis, has so far only been described in Asian countries. This study
      reports the first finding of Aichi virus in clinical specimens from Germany and
      Brazil. The nucleotide sequences of both a German and a Brazilian isolate were
      determined, analyzed, and compared to known Aichi sequences. The German strain
      turned out to be a member of genogroup A, while the Brazilian belonged to
      genogroup B. For a primary assessment of the epidemiological importance of Aichi
      virus in Germany, a panel of 485 German serum samples was screened for antibody
      to Aichi virus, and a seroprevalence of 76% was found.

PMID- 16421635
TI  - Inducible virus-mediated expression of a foreign protein in suspension-cultured
      plant cells.
AB  - Although suspension-cultured plant cells have many potential merits as sources of
      useful proteins, the lack of an efficient expression system has prevented using
      this approach. In this study, we established an inducible tomato mosaic virus
      (ToMV) infection system in tobacco BY-2 suspension-cultured cells to inducibly
      and efficiently produce a foreign protein. In this system, a modified ToMV
      encoding a foreign protein as replacement of the coat protein is expressed from
      stably transformed cDNA under the control of an estrogen-inducible promoter in
      transgenic BY-2 cells. Estrogen added to the culture activates an estrogen
      inducible transactivator expressed constitutively from the transgene and induces
      transcription and replication of viral RNA. In our experiments, accumulation of
      viral RNA and expression of green fluorescent protein (GFP) encoded in the virus
      were observed within 24 h after induction. The amount of GFP reached
      approximately 10% of total soluble protein 4 d after induction. In contrast,
      neither viral RNA nor GFP were detected in uninduced cells. The inducible virus
      infection system established here should be utilized not only for the expression
      of foreign proteins, but also for investigations into the viral replication
      process in cultured plant cells.

PMID- 16421636
TI  - Molecular characterization of human astroviruses isolated in Brazil, including
      the complete sequences of astrovirus genotypes 4 and 5.
AB  - Human astroviruses (HAstV) are recognized as an important cause of
      gastroenteritis in young children worldwide. This study describes the molecular
      characteristics of astroviruses isolated in Brazil, using RT-PCR and molecular
      sequencing of segments of all three viral ORFs. Genetic analysis of a 348
      nucleotide segment from ORF 2 demonstrated that the Brazilian isolates belong to
      HAstV genotypes 1 to 5 and 8. ORF 1b sequences displayed a high degree of
      nucleotide identity even between different genotypes, which disfavours HAstV
      genotyping in this region. ORF 1a sequence analysis classified all Brazilian
      samples as genogroup A. The complete sequences of HAstV genotype 4 (putative
      serotype 4) and genotype 5 (putative serotype 5) were determined for the first
      time.

PMID- 16421637
TI  - E1A genes of adenovirus type 2 and type 5 are expressed at different levels.
AB  - Adenoviruses are an extensively studied system for modeling oncogenesis and for
      experimental cancer therapy. The most commonly analyzed virus types are 2 and 5,
      and little distinction has been made between them in past studies. Adenoviruses
      used for therapeutic purposes are frequently hybrids between these types,
      including the prototype dl1520/Onyx015. We tested the replication of the wild
      type viruses WtD (a hybrid of the type 2 E1 region and type 5) and dl309 (type 5)
      in comparison with the mutants dl1520 (hybrid) and dl338 (type 5), the latter two
      lacking part of the E1B-55 kDa coding region. We found that the hybrid viruses
      replicated with considerably lower efficiency than their type 5 counterparts in
      H1299 cells (dl309:WtD = 3-4, dl338:dl1520 > 10). Moreover, adenovirus type 2 E1A
      expression from the hybrid viruses was strongly reduced in comparison to
      adenovirus type 5 E1A, as revealed by immunoblot analysis and RT-PCR, providing a
      potential explanation for the differences in virus yield. Differential E1A
      expression levels need to be taken into account for the construction of effective
      therapeutic viruses and when studying viral transformation.

PMID- 16421638
TI  - Vanilla mosaic virus isolates from French Polynesia and the Cook Islands are
      Dasheen mosaic virus strains that exclusively infect vanilla.
AB  - Sequence was determined for the coat protein (CP) gene and 3' non-translated
      region (3'NTR) of two vanilla mosaic virus (VanMV) isolates from Vanilla
      tahitensis, respectively from the Cook Islands (VanMV-CI) and French Polynesia
      (VanMV-FP). Both viruses displayed distinctive features in the N-terminal region
      of their CPs; for VanMV-CI, a 16-amino-acid deletion including the aphid
      transmission-related DAG motif, and for VanMV-FP, a stretch of GTN repeats that
      putatively belongs to the class of natively unfolded proteins. VanMV-FP CP also
      has a novel DVG motif in place of the DAG motif, and an uncommon Q//V protease
      cleavage site. The sequences were compared to a range of Dasheen mosaic virus
      (DsMV) strains and to potyviruses infecting orchids. Identity was low to DsMV
      strains across the entire CP coding region and across the 3'NTR, but high across
      the CP core and the CI-6K2-NIa region. In accordance with current ICTV criteria
      for species demarcation within the family Potyviridae, VanMV-CI and VanMV-FP are
      strains of DsMV that exclusively infect vanilla.

PMID- 16421639
TI  - [Early diagnosis of arthritis and spondyloarthritis within the framework of
      integrated health care in Lower Saxony].
AB  - In September 2005, the Collaborative Arthritis Center in Hannover, the Hannover
      Medical School, general practitioners, rheumatologists in private practice, the
      League against Rheumatism in Lower Saxony (Rheuma-Liga Niedersachsen, a regional
      patient self-help organization), the State Pension Authority (Deutsche
      Rentenversicherung Braunschweig-Hannover) and a health insurance fund
      (Kaufmannische Krankenkasse), in collaboration with the Physician's Association
      of Lower Saxony, entered a contract for integrated health care in rheumatology in
      Lower Saxony. The agreement aims at patients with early arthritis or
      spondyloarthritis. Through close collaboration between primary health care
      physicians and rheumatologists, the diagnosis of arthritis or spondyloarthritis
      should be made soon after disease manifestation and an adequate therapy
      initiated. The article describes the background and contents of the contract.

PMID- 16421640
TI  - [Pneumocystis jiroveci pneumonia (PcP) in patients with rheumatic diseases: case
      report and review].
AB  - A 74-year-old female patient with rheumatoid arthritis was diagnosed with
      Pneumocystis jiroveci pneumonia (PcP) following therapy with methotrexate and
      prednisone. Although bactrim treatment was initiated and PcP was not detected by
      a control bronchoalveolar lavage, the patient died. The precise cause of death
      remains unknown. As this case illustrates, PcP must be considered as a
      differential diagnosis in immunocompromised patients with rheumatic disease. The
      typical course, diagnosis, prophylaxis and treatment of PcP in this patient group
      are discussed.

PMID- 16421641
TI  - [Risk of infection during treatment with tumor necrosis factor-alpha inhibitors].
AB  - Tumor necrosis factor-alpha (TNF) is essential for immune defense. TNF plays a
      major role in the recruitment of inflammatory cells to the site of infection and
      in the formation and maintenance of granulomas. In addition, it plays a primary
      and detrimental role in chronic autoimmune diseases. Drugs that inhibit TNF are
      effective in the treatment of inflammatory rheumatic and autoimmune diseases.
      However, the three currently available TNF antagonists (etanercept, infliximab
      and adalimumab) decrease host resistance to granulomatous diseases such as
      tuberculosis. The incidence of tuberculosis in patients treated with TNF
      antagonists is higher than in the general population. There are a number of case
      reports describing the association of TNF-antagonists and the presentation of
      other infectious diseases such as histoplasmosis, listeriosis,
      coccidioidomycosis, candidiasis and aspergillosis. These case reports, however,
      are anecdotal. Nonetheless, patients treated with TNF antagonists are
      immunocompromised and infectious diseases are most likely more frequent and may
      present differently than expected. In this review, we describe the role of TNF in
      constraining infectious diseases, the difference between the three available TNF
      antagonists, and we discuss the relevant clinical data published in the
      literature as related to the risk of anti-TNF therapy for infectious diseases.

PMID- 16421642
TI  - [Infectious spondylitis].
AB  - Infectious spondylitis usually involves osteomyelitis in two adjacent vertebral
      bodies and the intervertebral disc (spondylodiscitis). The most common location
      is the lumbar spine, followed by the thoracic spine. Symptoms are nonspecific,
      leading to a delay in diagnosis, in many cases, of several weeks. A large number
      of infectious agents can cause vertebral osteomyelitis, usually reaching the
      vertebra by hematogenous spread. The most commonly isolated agent is
      Staphylococcus aureus. Spondylitis remains the most common skeletal manifestation
      of tuberculosis. As with other forms of osteomyelitis, microbiological diagnosis
      is essential for the choice of adequate therapy. The majority of cases can be
      cured with antibiotic therapy alone.

PMID- 16421643
TI  - [Diagnosis and treatment of prosthetic joint infections].
AB  - Prosthetic replacement surgery for hip, knee, shoulder, and elbow joints has
      become commonplace due to the great success of these procedures in restoring
      function to persons disabled by arthritis. One of the most feared complications
      is prosthetic joint infection, which is associated with significant morbidity and
      health care costs. The pathogenesis of prosthetic joint infections is influenced
      by microorganisms growing in biofilms, making these infections difficult to
      diagnose and eradicate. Low-grade infections are often manifest as early
      loosening with or without pain. They are therefore difficult to distinguish from
      aseptic failure. For an accurate diagnosis of prosthetic joint infections, a
      combination of preoperative and intraoperative tests is usually needed.
      Underlying rheumatologic disease can lead to periprosthetic inflammatory changes
      in tissue. Therefore, only the culture of the microorganism is definitive proof
      of infection. Successful treatment requires long-term antimicrobial therapy,
      ideally with an agent acting on adhering stationary-phase microorganisms,
      combined with an adequate surgical procedure. In this article, the epidemiology,
      pathogenesis, diagnosis and treatment of prosthetic joint infections are
      reviewed. We focus on difficult diagnostic aspects in the context of underlying
      rheumatologic disease.

PMID- 16421645
TI  - Urticaria and angiedema-like skin reactions in a patient treated with adalimumab.
AB  - Specific inhibition of the cytokine tumor necrosis factor alpha has resulted in
      significant clinical and laboratory improvement of patients with chronic
      inflammatory diseases of Th1 phenotype. Etanercept is a recombinant fusion
      protein of two p75 soluble receptors, while infliximab is a chimeric monoclonal
      antibody. Both have been considered to be immunogenic and cause various immune
      mediated skin reactions. On the other hand, adalimumab, a human monoclonal
      antibody, was expected to cause little or no immune-mediated skin reactions.
      Herein, we report a patient with rheumatoid arthritis treated with adalimumab,
      who after the seventh injection, developed angiedema affecting the lips and face,
      as well as an urticaria-like skin reaction affecting the trunk. These reactions
      were followed by hypotension. The patient was treated appropriately and after 2
      h, the rashes and the edema disappeared and the patient gradually recovered
      completely. Adalimumab was discontinued.

PMID- 16421644
TI  - Multiple small pulmonary emboli associated with transient antiphospholipid
      syndrome in human Parvovirus B19 infection.
AB  - Antiphospholipid antibodies (aPL) have been reported to occur in several
      conditions other than antiphospholipid syndrome, including infections. We herein
      report the case of a 21-year-old Japanese woman with Parvovirus B19 infection,
      who developed multiple pulmonary emboli associated with aPL, a lupus
      anticoagulant and IgM anticardiolipin antibody. Eight weeks later,
      antiphospholipid antibodies spontaneously disappeared and normal pulmonary flow
      was observed. Considering the high prevalence of Parvovirus B19 infection, we
      should be aware of thrombosis associated with transient aPL antibodies in this
      infectious disease.

PMID- 16421646
TI  - Reliability and validity of the Italian version of the Chronic Pain Grade
      questionnaire in patients with musculoskeletal disorders.
AB  - The aim of this study is to analyse the psychometric properties of the Italian
      version of the Chronic Pain Grade (CPG) questionnaire within a population of
      chronic musculoskeletal pain patients. The CPG questionnaire was adapted
      following the translation and back-translation methodologies. There were 576
      patients with chronic musculoskeletal pain. Internal consistency was checked by
      the Cronbach's alpha coefficient. Construct validity was analysed by performing
      principal component factor analysis and by comparing CPG dimensions and subscales
      with the SF-36 questionnaire. Discriminant validity was assessed by comparing the
      CPG and SF-36 dimensions in patients with and without other health conditions.
      Factor analysis yielded two factors which accounted for 76.4% of the variance of
      the questionnaire. Both subscales of the CPG showed satisfying to good internal
      consistency. Cronbach's alpha was 0.89 for the first factor 'Disability Score'
      (58.72% of the explained variance) and 0.81 for the second factor 'Characteristic
      Pain Intensity' (17.70% of the explained variance). Item-total correlations for
      the subscales were moderate up to high (from 0.500 to 0.771). In comparison with
      the SF-36, the expected correlations were found when comparing items measuring
      similar constructs, supporting the concepts of convergent construct validity.
      Discriminant validity, assessed by comparing the CPG dimensions in patients with
      and without other health conditions, showed that the CPG shows moderate
      association with the presence of co-morbidities. Furthermore, the CPG Disability
      Score was inversely correlated (p=0.01) to years of formal education. In
      conclusion, the Italian version of the CPG questionnaire has shown to be valid
      and reliable for evaluating the severity of chronic musculoskeletal pain, with
      metric properties in agreement with the original, widely used version.

PMID- 16421647
TI  - Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with
      established osteoporosis.
AB  - This study compared the clinical efficacy, safety, and tolerability of daily
      subcutaneous injections of teriparatide and salmon calcitonin in the treatment of
      postmenopausal women with established osteoporosis in Taiwan. This 6-month,
      multicenter, randomized, controlled study enrolled 63 women with established
      osteoporosis. They were randomized to receive either teriparatide 20 microg or
      calcitonin 100 IU daily in an open-label fashion. Lumber spine, femoral neck,
      total hip bone mineral density (BMD), and biochemical markers of bone turnover
      were measured, and adverse events and tolerability were recorded. The results at
      6 months showed that patients using teriparatide had larger mean increases in
      spinal BMD than those who used calcitonin (4.5% vs. 0.1%), but the BMD changes in
      these two groups at the femoral neck and the total hip were not significant.
      There were also larger mean increases in bone markers in the teriparatide group
      than in the calcitonin group (bone specific alkaline phosphatase 142% vs. 37%;
      osteocalcin 154% vs. 23%). We conclude that teriparatide has more positive
      effects on bone formation than salmon calcitonin, as shown by the larger
      increments of lumbar spine BMD and bone formation markers, and caused only mild
      adverse events and no significant change in liver, kidney or hematological
      parameters. Compared with the published global results, teriparatide seems to be
      equally effective and safe to use in this Asian population.

PMID- 16421649
TI  - The effects of expressive writing on adjustment to HIV.
AB  - Previous research suggests that writing about stressful experiences results in
      better health and psychological well-being. In the present study, a multi-ethnic
      sample of 79 HIV-positive women and men participated in a structured interview,
      and wrote about either their deepest thoughts and feelings about living with HIV
      (expressive writing) or their activities in the last 24 hr (control). Sixty-two
      participants returned for the 2-month follow-up and 50 returned for the 6-month
      follow-up interview. Oral fluid samples of beta2-microglobulin were taken at the
      baseline and follow-up assessments to examine the immunological effects of
      writing. No effects of writing condition were found, but expressive writing
      participants who included increasing insight/causation and social words in their
      writing had better immune function and reported more positive changes at follow
      up. Results suggest that cognitive processing and changes in social interactions
      may be critical to the benefits of writing.

PMID- 16421650
TI  - Lipodystrophy severity does not contribute to HAART nonadherence.
AB  - Lipodystrophy severity among 77 people living with HIV/AIDS (PHA) with body fat
      redistribution was not related to antiretroviral adherence including doses missed
      during the previous month, categorical rating of maximal adherence, and the PMAQ7
      adherence behavior scale. Two thirds of the sample reported submaximal adherence,
      19% missing more than two doses, but adherence behavior ratings reflected good
      overall adherence. Overall symptom burden, convenience of regimen schedule and
      remembering to organize and take antiretroviral doses, but not regimen adaptation
      or treatment support, were associated with adherence. Remembering was most
      strongly related to adherence indicators, retaining statistical significance in
      adjusted multivariate regression analyses.

PMID- 16421651
TI  - Rural-to-urban migrants and the HIV epidemic in China.
AB  - China is the next probable frontier for the global HIV epidemic. Central to this
      anticipated growth of the epidemic is the nation's new and growing population of
      rural-to-urban migrants. Although there are an estimated 120 million migrants,
      little information is available about their social and cultural context of their
      lives in urban areas and their HIV-related perceptions and behaviors. On the
      basis of the in-depth individual interviews conducted among 90 rural-to-urban
      migrants in 2 major Chinese cities, Beijing and Nanjing, this qualitative study
      was designed to explore these issues with a particular focus on their relevance
      to sexual transmission of HIV. The findings suggest an urgent need for HIV/STI
      prevention programs that address the cultural, social, and economic constraints
      facing the migrant population in China.

PMID- 16421652
TI  - Associations among health behaviors and time perspective in young adults: model
      testing with boot-strapping replication.
AB  - Previous research suggests that time perspective relates to health behavior;
      however, researchers have frequently employed inconsistent operational
      definitions and have often used projective or unpublished measures. The Zimbardo
      Time Perspective Inventory was created to provide a sound, objective measure of
      five distinct time perspective components. We examined the independent prediction
      of both risky and protective health behaviors from future, hedonistic, and
      fatalistic time perspective in 1,568 undergraduates using the Zimbardo Time
      Perspective Inventory. Health behaviors included alcohol, drug, tobacco, and seat
      belt use, sex behaviors, and exercise. Future time perspective was related to
      increased protective and decreased risky health behaviors, whereas hedonism
      exhibited an opposite pattern though was a stronger predictor; fatalism was
      related only to health-destructive behaviors. Gender interactions reveal that
      hedonism is a stronger predictor of risky health behaviors for females.

PMID- 16421653
TI  - Youth development, community engagement, and reducing risk behavior.
AB  - This article examines behaviors and attitudes associated with the "Youth
      Development Model," widely cited as a means of promoting resistance among young
      people to adverse environmental influences. Focusing on tobacco use as an example
      of high-risk behavior, the research reported here (1) tests the statistical
      independence of individual Youth Development Model dimensions, and (2) assesses
      their relationships to tobacco-related attitudes and behavior. The "engagement"
      dimension, reflecting strong ties of youths with the broader community, most
      clearly distinguishes risk reduction interventions based on the Youth Development
      Model. Two exploratory studies indicate that, among dimensions associated with
      this model, engagement is the least readily measurable and the least consistent
      and robust as a predictor of tobacco-related attitudes and behavior. Editors'
      Strategic Implications: The authors present an important challenge to the
      increasingly prevalent Youth Development Model. The results of the two studies
      call for a better conceptual and operational understanding of engagement, which
      must precede its successful application in reducing risky behavior among young
      people.

PMID- 16421654
TI  - Research to practice: efforts to bring effective prevention to every community.
AB  - This manuscript describes the pioneering efforts of the Substance Abuse and
      Mental Health Services Administration's attempts to catalog knowledge, support,
      and further evaluate the application of evidence-based prevention. The paper
      begins with a discussion of scientific inquiry, including discussion of cause-and
      effect relationships, theory that is useful in explaining those relationships,
      and suggestion of the opportunities and limitations of research in these and
      other areas. The authors then describe a system that has been introduced by the
      Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for
      Substance Abuse Prevention (CSAP) to systematically access and review applied
      research efforts in drug abuse prevention and related fields. In addition to
      identifying the key elements of this National Registry of Effective Prevention
      Programs (NREPP), the authors provide a brief history of prior efforts that have
      led us to this point.

PMID- 16421656
TI  - FAST and the arms race: the interaction of group aggression and the families and
      schools together program in the aggressive and delinquent behaviors of inner-city
      elementary school students.
AB  - This study applies a multi-player arms race model to peer contagion in the
      aggressive and delinquent behaviors of inner-city elementary school students.
      Because this model of peer contagion differs from the usual model based on
      positive reinforcement of delinquent behavior, it raises the possibility that the
      persistent finding of iatrogenic effects of group treatment might not apply to
      group treatment of elementary school children if the possibility of aggressive
      behavior in the group is limited. One way of limiting aggressive behavior is to
      include parents in the groups. The study therefore applies the model to groups of
      elementary school students assigned to Families and Schools Together (FAST; a
      group treatment that includes parental participation) or to an intervention
      focused on individual families. The model effectively describes the relationship
      between group averages of aggressive behavior in the classroom and aggressive and
      delinquent behavior outside the classroom for those students assigned to the
      individual intervention. The model fits those children assigned to FAST less
      well, suggesting that FAST may make it less likely that aggressive and delinquent
      behavior is generalized outside of aggressive classroom settings. Editors'
      Strategic Implications: The authors draw on evolutionary biology, developmental
      psychology, sociology, and learning theory to present an innovative prevention
      model and test the promising FAST program. Using longitudinal data from 403
      children, their parents, and their teachers, the authors describe how FAST may
      interfere with the process of escalating aggression.

PMID- 16421655
TI  - Cardiovascular health status and health risk assessment method of preference
      among worksite employees.
AB  - We investigated whether employees (n = 62) selecting a self-report Health Risk
      Assessment (HRA) would be at increased CVD risk compared to employees (n = 114)
      choosing an HRA with measurement of cardiovascular (CVD) health indicators.
      Participants were mostly middle-aged (44.1 +/- 0.8 yr) men (71.6%) displaying
      borderline features of the cardiometabolic syndrome. Although there were no
      significant differences between the groups regarding their measured CVD health
      status or self-reported lifestyle habits, employees in both groups consistently
      over-stated their level of cardiovascular health. Contrary to reports in the
      literature, cardiovascular health status did not appear to influence employee HRA
      method of preference.Editors' Strategic Implications: These findings await
      replication in other samples, both more diverse and less self-selected.
      Nonetheless, the authors' methods and their conclusions about workers' over
      estimation of their health and the lack of differences across assessment methods
      will be useful to employers, health professionals, and all practitioners with an
      interest in health risk assessments.

PMID- 16421657
TI  - Factors influencing treatment compliance among Turkish people at risk for stroke.
AB  - Successful management of stroke risk factors depends on adequate knowledge and
      self-care. The purpose of this study was to examine the factors affecting
      treatment compliance among people with modifiable stroke risks. We evaluated
      modifiable risk factors of stroke, recognition of these factors by patients, and
      patients' compliance with treatment in a teaching hospital. Semi-structured
      questionnaires were completed using face-to-face interview techniques. A majority
      (58.3%) of patients were aware of their risk factors for stroke. Awareness of
      risk factors was statistically significant for the participants carrying risk
      factors such as heart disease and hyperlipidemia. Compliance of the participants
      with treatment was mainly affected by the recognition that their disease could be
      a risk factor for stroke. Awareness of the presence of multiple risk factors and
      nonsmoker status were positively associated with treatment compliance. Editors'
      Strategic Implications: The authors provide evidence that the recognition of risk
      factors and informative healthcare education may decrease the likelihood of and
      the recurrence of stroke. Future research should document efforts to inform high
      risk patients and measure their compliance with recommendations.

PMID- 16421658
TI  - Participation in "parents who care": predicting program initiation and exposure
      in two different program formats.
AB  - Predictors of participation and exposure across two formats of a universal
      prevention program are examined here. Families of 225 8th-grade students,
      balanced by race (African American and European American) and gender, were
      assigned to a parent and adolescent group format (PAG) or a self-administered
      format (SA). Logistic regression showed greater program initiation in SA than in
      PAG. Hierarchical regression showed only one variable (parent high-risk behavior)
      to be associated with lower program exposure in the self-administered format. In
      contrast, demographic variables (e.g., being African American) predicted lower
      exposure in PAG. Overall, the findings of this study were notable in that most of
      the variables that have been identified in past research as lowering
      participation rates were not related to program initiation or level of exposure
      to either format of Parents Who Care. Further, the self-administered format may
      be particularly useful to increase program participation for families, even those
      who are traditionally difficult to reach. Editors' Strategic Implications: The
      authors make a promising contribution to the literature on program engagement by
      presenting experimental data highlighting different risk factors for
      nonparticipation across program formats. Their discussion of barriers will help
      program designers and practitioners decide on the most appropriate strategies for
      the dissemination of prevention-related materials to parents.

PMID- 16421659
TI  - Barostat measurement of rectal compliance and capacity.
AB  - PURPOSE: Fecal continence requires relaxation of the rectal wall and a reservoir
      of adequate capacity. Rectal compliance provides an assessment of rectal wall
      stiffness; however, compliance is also affected by rectal capacity. We developed
      and validated a barostat measurement of rectal capacity. By accounting for
      variation in rectal capacity, we aimed to improve the inconsistent relationship
      between rectal compliance, sensation, and continence reported in the literature.
      METHOD: Barostat measurements of rectal compliance and capacity were validated in
      41 healthy, continent subjects. Slow staircase (0-40 mmHg) and rapid phasic (12
      40 mmHg) distentions were performed on two separate days, filling sensations were
      assessed by visual analog score. A stool substitute retention test of rectal
      filling sensation and continence was performed. RESULTS: Variance of volume
      measurements decreased with pressure comparing conditioning vs. index
      distentions, staircase vs. phasic distentions, and measurements on different days
      (all P < 0.001). Correction for rectal capacity measured at 40 mmHg reduced the
      "normal range" of compliance measurements (P < 0.01) but not vice versa. Compared
      with unadjusted volume measurements, normalized rectal volume (percentage filling
      relative to rectal capacity) improved the description of rectal sensation visual
      analog score (P < 0.01). Rectal capacity correlated with filling sensations and
      the volume retained on retention testing (P < 0.01). CONCLUSION: Barostat
      measurements of rectal capacity at 40 mmHg are highly reproducible and not
      affected by distention protocol. The assessment of rectal capacity complements
      that of rectal compliance. Correction for rectal capacity provides an assessment
      of rectal wall stiffness independent of rectal geometry and improves the
      association of barostat volume measurements with rectal sensitivity and
      continence.

PMID- 16421660
TI  - Accumulation profile of frameshift mutations during development and progression
      of colorectal cancer from patients with hereditary nonpolyposis colorectal
      cancer.
AB  - PURPOSE: Role and timing of frameshift mutations during carcinogenesis in
      hereditary nonpolyposis colorectal cancer have not been examined. This study was
      designed to clarify the relationship between frameshift mutations and
      clinicopathologic features in colorectal cancer from patients with hereditary
      nonpolyposis colorectal cancer. METHODS: Thirty-one colorectal cancers from
      patients with hereditary nonpolyposis colorectal cancer at different
      clinicopathologic stages were analyzed for frameshift mutation in 18 genes.
      RESULTS: The frameshift mutations of the ACVR2 and PTHLH genes were found to have
      an extremely high frequency (94-100 percent) in all pathologic stages, and
      mutation of the MARCKS gene also was high (94 percent) in Dukes B and C cancers.
      These frequencies were higher than the frequency of TGFbetaRII gene inactivation
      (64-88 percent). Mutations of the hMSH3, TCF4, CASP5, RIZ, RAD50, and MBD4 genes
      were comparatively frequent (>35 percent) in all stages. Frequencies of
      inactivation of the MARCKS, BAX, IGFIIR, and PTEN genes were significantly higher
      in Dukes B and C cancers than in Dukes A cancer (P < 0.05). The number of
      accumulated frameshift mutations was larger in Dukes B and C cancers (9.4) than
      in Dukes A cancer (6.8) (P = 0.003). CONCLUSIONS: The present data suggest that
      the disruption of the transforming growth factor-beta super-family signaling
      pathway by the alteration of the ACVR2 and/or TGFbetaRII genes and the disruption
      of antiproliferative function by the PTHLH gene alteration contribute to the
      development of early colorectal cancer. Moreover, the further accumulation of
      alterations in the MARCKS, BAX, IGFIIR, and PTEN genes seem to be associated with
      progression from early to advanced colorectal cancer from patients with
      hereditary nonpolyposis colorectal cancer.

PMID- 16421661
TI  - Preoperative oral immune-enhancing nutritional supplementation corrects TH1/TH2
      imbalance in patients undergoing elective surgery for colorectal cancer.
AB  - PURPOSE: Recent studies have shown that the type 1/2 CD4+ T cell (Th1/Th2)
      balance shifts toward Th2 dominance in cancer-bearing state or by surgical
      stress. Perioperative immunonutrition is reported to improve the outcome in
      patients with gastrointestinal cancer. This study was designed to investigate
      whether preoperative immunonutrition corrects the impaired Th1/Th2 balance in the
      perioperative period. METHODS: Thirty-six patients with colorectal cancer were
      prospectively divided into two groups as follows: preoperative oral intake
      supplementation with a formula enriched with arginine, omega-3 fatty acids and
      ribonucleic acid for five days (supplemented group; n = 19); and (control group;
      n = 17). Blood sampling was performed before supplementation, on the morning of
      surgery, and 3, 7, and 14 days postoperatively. The proportions of CD4+ T cells
      producing intracellular cytokines (interferon-gamma and interleukin-4) were
      measured by flow cytometry. RESULTS: In the preoperative period, the proportions
      of CD4+ T cells producing interleukin-4 significantly decreased and Th1/Th2 ratio
      significantly increased on the morning of surgery compared with those before
      supplementation. In the postoperative period, the proportions of CD4+ T cells
      producing interferon-gamma in both groups maintained the preoperative level. The
      proportions of CD4+ T cells producing interleukin-4 in the control group showed a
      gradual increase from the preoperative level, which implies Th2 dominant shift.
      In contrast, the supplemented group maintained the preoperative level of Th1/Th2
      ratio. CONCLUSIONS: Preoperative immunonutrition corrects impaired Th1/Th2
      balance in both cancer-bearing state and the postoperative period. This
      correction may be one of the important determinants of the clinical benefits of
      immunonutrition.

PMID- 16421662
TI  - A comparison of POSSUM, P-POSSUM and colorectal POSSUM for the prediction of
      postoperative mortality in patients undergoing colorectal resection.
AB  - PURPOSE: POSSUM (Physiologic and Operative Severity Score for enUmeration of
      Morbidity & Mortality) and P-POSSUM have been validated as scoring tools for the
      prediction of postoperative complications in general surgical patients. More
      recently a colorectal-specific POSSUM has been developed for mortality
      prediction. This study was designed to evaluate and compare the accuracy for
      mortality prediction of POSSUM, P-POSSUM, and colorectal POSSUM after major and
      complex major colorectal procedures. METHODS: The relationship between the
      observed and expected morbidity and mortality was examined in 347 consecutive
      patients (321 elective, 26 urgent) undergoing a major or complex major colorectal
      resection using POSSUM, P-POSSUM, and Colorectal POSSUM. The accuracy of using
      these scoring tools to predict mortality was assessed using Receiver Operator
      Characteristic curve analysis. RESULTS: A total of 347 consecutive patients
      (median age, 69 (range, 34-92) years) were assessed. Seventy-one patients (20.5
      percent) suffered a postoperative complication and 15 patients (4.3 percent)
      died. The observed: expected POSSUM ratio for morbidity was 0.71 and mortality
      0.68. The area under curve from Receiver Operator Characteristic curve analysis
      for POSSUM was 0.752. The observed:expected mortality ratio for P-POSSUM was
      0.71, and the area under curve from Receiver Operator Characteristic curve
      analysis was 0.749. The observed:expected mortality ratio for colorectal POSSUM
      was 0.75, and the area under the curve from Receiver Operator Characteristic
      curve analysis was 0.781. CONCLUSIONS: Colorectal POSSUM provides comparable
      prediction of mortality risk after colorectal resection compared with POSSUM and
      P-POSSUM.

PMID- 16421663
TI  - Practice parameter for the detection of colorectal neoplasms: an interim report
      (revised).

PMID- 16421664
TI  - Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas.
AB  - PURPOSE: Long-term closure rates of anorectal fistulas using fibrin glue have
      been disappointing, possibly because of the liquid consistency of the glue. A
      suturable bioprosthetic plug (Surgisis, Cook Surgical, Inc.) was fashioned to
      close the primary opening of fistula tracts. A prospective cohort study was
      performed to compare fibrin glue vs. the anal fistula plug. METHODS: Patients
      with high transsphincteric fistulas, or deeper, were prospectively enrolled.
      Patients with Crohn's disease or superficial fistulas were excluded. Age, gender,
      number and type of fistula tracts, and previous fistula surgeries were compared
      between groups. Under general anesthesia and in prone jackknife position, the
      tract was irrigated with hydrogen peroxide. Fistula tracts were occluded by
      fibrin glue vs. closure of the primary opening using a Surgisis anal fistula
      plug. RESULTS: Twenty-five patients were prospectively enrolled. Ten patients
      underwent fibrin glue closure, and 15 used a fistula plug. Patient's age, gender,
      fistula tract characteristics, and number of previous closure attempts was
      similar in both groups. In the fibrin glue group, six patients (60 percent) had
      persistence of one or more fistulas at three months, compared with two patients
      (13 percent) in the plug group (P < 0.05, Fisher exact test). CONCLUSIONS:
      Closure of the primary opening of a fistula tract using a suturable biologic anal
      fistula plug is an effective method of treating anorectal fistulas. The method
      seems to be more reliable than fibrin glue closure. The greater efficacy of the
      fistula plug may be the result of the ability to suture the plug in the primary
      opening, therefore, closing the primary opening more effectively. Further
      prospective, long-term studies are warranted.

PMID- 16421665
TI  - Analysis of dissolution data using modified versions of Noyes-Whitney equation
      and the Weibull function.
AB  - PURPOSE: The aim of the study is to develop modified, branched versions of the
      Noyes-Whitney and the Weibull equations, including explicitly the solubility/dose
      parameter, for the analysis of dissolution data, which reach the plateau either
      at infinite or finite time. METHODS: The modified Weibull function is applied to
      the analysis of experimental and literature dissolution data. To demonstrate the
      usefulness of the mathematical models, two model drugs are used: one highly
      soluble, metoprolol, and one relatively insoluble, ibuprofen. RESULTS: The models
      were fitted successfully to the data performing better compared with their
      classic versions. The advantages of the use of the models presented are several.
      They fit better to a large range of datasets, especially for fast dissolution
      curves that reach complete dissolution at a finite time. Also, the modified
      Weibull presented can be derived from differential equations, and it has a
      physical meaning as opposed to the purely empirical character of the original
      Weibull equation. The exponent of the Weibull equation can be attributed to the
      heterogeneity of the process and can be explained by fractal kinetics concepts.
      Also, the solubility/dose ratio is present explicitly as a parameter and allows
      to obtain estimates of the solubility even when the dissolution data do not reach
      the solubility level. CONCLUSION: The use of the developed branched equations
      gives better fittings and specific physical meaning to the dissolution
      parameters. Also, the findings underline the fact that even in the simplest,
      first-order case, the speed of the dissolution process depends on the dose, a
      fact of great importance in biopharmaceutic classification for regulatory
      purposes.

PMID- 16421667
TI  - Determination of the surface free energy of crystalline and amorphous lactose by
      atomic force microscopy adhesion measurement.
AB  - PURPOSE: This study was conducted to accurately measure the dispersive surface
      free energy of lactose solids in ordered and disordered states. METHODS: Atomic
      force microscopy (AFM) was used to determine the contact adhesion force between
      an AFM tip and lactose under low humidity (ca. 1% RH). The geometry of the tip
      contacting apex was characterized by scanning a porous aluminum film with
      ultrasharp spikes (radius 2-3 nm). A sphere vs. flat surface model was employed
      to relate the adhesion force determined to the surface energy based upon the
      Johnson-Kendal-Roberts theory. Spray-dried amorphous lactose in a compressed-disk
      form and single crystals of alpha-lactose monohydrate were prepared as model
      samples. RESULTS: The condition of the smooth sample surface and sphere-shaped
      tip used was shown to be appropriate to the application of the JKR model. The
      surface energy of crystalline [(0,-1,-1) face] and amorphous lactose was
      determined to be 23.3 +/- 2.3 and 57.4 +/- 7.9 mJ m(-2), respectively.
      CONCLUSIONS: We have demonstrated the capability of AFM to measure the dispersive
      surface free energy of pharmaceutical materials directly through a blank probe at
      the nanometer scale. These data, although consistent with results from more
      traditional methods, illustrate some unique attributes of this approach, namely,
      surface energies are directly derived from solid-solid interactions, measurements
      may be made on specific crystalline faces, and the potential exists to identify
      the submicron heterogeneity of organic solids in terms of their molecular energy
      states (such as ordered and disordered lactose).

PMID- 16421666
TI  - Advances in the use of tocols as drug delivery vehicles.
AB  - There has been increasing interest in recent years in the drug delivery
      applications of tocols and their derivatives. Their biocompatibility and
      potential to deliver both poorly soluble and water-soluble drugs make tocols
      attractive as drug delivery vehicles. This review article will focus primarily on
      topical, oral, and parenteral drug administration using tocols, although other
      routes of delivery such as pulmonary and nasal will also be discussed. After an
      overview of the tocol structures, physicochemical properties with emphasis on
      their solvent properties, functions, and metabolism, specific case studies will
      be discussed where tocols have been successfully used in topical, oral, and
      parenteral drug formulations and marketed drug products. Case studies will be
      extended to those where tocol-based formulations were administered pulmonarily
      and nasally. As more clinical data and marketed drug products emerge, the utility
      and therapeutic value of tocols will certainly increase.

PMID- 16421668
TI  - Effect of high-frequency jet ventilation on oxygenation during one-lung
      ventilation in patients undergoing thoracic aneurysm surgery.
AB  - PURPOSE: To evaluate the effect of high-frequency jet ventilation (HFJV) and
      continuous positive airway pressure (CPAP) on oxygenation and the shunt fraction
      (Qs/Qt) during one-lung ventilation (OLV). METHODS: Twenty-five patients who were
      undergoing resection of a descending aortic aneurysm were studied. Arterial
      oxygenation, Qs/Qt, and hemodynamics were evaluated just before the initiation of
      OLV (T1), 15 min after OLV (T2), and 15 min (T3) and 30 min (T4) after the
      application of HFJV or CPAP to the nondependent lung. RESULTS: There were no
      significant changes in the mean arterial blood pressure (MAP), heart rate (HR),
      central venous pressure (CVP), or mixed venous partial pressure of oxygen
      throughout this study. The arterial partial pressure of oxygen (Pa(O2)) values
      after the application of HFJV or CPAP increased significantly, from 173.8 +/-
      39.6 mmHg (T2) to 344.1 +/- 87.9 mmHg (T3) and 359.9 +/- 82.4 mmHg (T4) in the
      HFJV group (P < 0.05), and from 153 +/- 38.5 mmHg (T2) to 243 +/- 48.5 mmHg (T3)
      and 249.7 +/- 55.0 mmHg (T4) in the CPAP group (P < 0.05). The shunt fraction
      decreased significantly after the initiation of HFJV or CPAP, from 38.7% +/- 8.9%
      (T2) to 27.0% +/- 8.0% (T3) and 25.9% +/- 8.7% (T4) in the HFJV group (P < 0.05),
      and from 44.6% +/- 8.6% (T2) to 34.3% +/- 10.2% (T3) and 32.6% +/- 8.5% (T4) in
      the CPAP group (P < 0.05). The arterial saturation of oxygen (Sa(O) (2))
      increased significantly after the application of either HFJV or CPAP (P < 0.05).
      CONCLUSIONS: Both HFJV and CPAP can improve oxygenation during OLV.

PMID- 16421669
TI  - Clinical effects of a neutrophil elastase inhibitor, sivelestat, in patients with
      acute respiratory distress syndrome.
AB  - PURPOSE: We assessed the effects of a neutrophil elastase inhibitor, sivelestat,
      on respiratory and organ functions as well as on the mortality of patients with
      acute respiratory distress syndrome (ARDS) associated with systemic inflammatory
      response syndrome (SIRS). METHODS: We retrospectively divided 25 patients who
      fulfilled the diagnostic criteria for SIRS and ARDS into two groups. One group (S
      group, n = 12) received a continuous infusion of sivelestat (0.2 mg.kg(-1).h(
      1)), and the other did not (C group, n = 13). RESULTS: Between days 1 and 10, the
      Pa(O2)/FI(O2) ratio in the S group significantly improved from 119.1 +/- 51.1 to
      214.4 +/- 88.2 mmHg (P < 0.05). Furthermore, the S group spent significantly
      fewer days on a ventilator than the C group (16.7 +/- 5.8 vs 26.6 +/- 14.3 days;
      P < 0.05). The length of the intensive care unit stay was also significantly
      shorter for the S group than for the C group (18.7 +/- 4.9 vs 27.5 +/- 13.5 days;
      P < 0.05). However, the mortality rate at 29 days did not statistically differ
      between the two groups. CONCLUSION: Our results suggested that sivelestat has a
      beneficial effect only on the pulmonary function of ARDS patients with SIRS.

PMID- 16421671
TI  - Effects of L-type Ca2+ channel modulation on direct myocardial effects of
      diazepam and midazolam in adult rat ventricular myocytes.
AB  - PURPOSE: Our objective was to determine whether an L-type Ca2+ channel modulation
      could alter myocardial depression induced by midazolam or diazepam in adult rat
      ventricular myocytes. METHODS: Freshly isolated rat ventricular myocytes were
      loaded with fura-2/AM and field-stimulated (0.3 Hz) at 28 degrees C. Amplitude
      and timing of intracellular Ca2+ concentration ([Ca2+]i) and myocyte shortening
      were simultaneously monitored in individual cells. RESULTS: Midazolam (3-100
      microM) caused a decrease in both peak [Ca2+]i and shortening. Diazepam (30, 100
      microM) increased myocyte shortening and peak [Ca2+]i; however, higher
      concentration of diazepam (300 microM) decreased shortening and peak [Ca2+]i. Bay
      K 8644 (0.01-10 microM), an L-type Ca2+ channel agonist, caused dose-dependent
      increases in peak [Ca2+]i and shortening. In contrast, verapamil (0.1-50 microM),
      an L-type Ca(2+) channel antagonist, caused dose-dependent decreases in peak
      [Ca2+]i and shortening. Dose-response curves to benzodiazepines on peak [Ca2+]i
      and shortening were not affected by pretreatment with Bay K 8644 (0.1 microM) or
      verapamil (1 microM). Diazepam (30, 100 microM), but not midazolam (3-30 microM),
      increased shortening and [Ca2+]i in the presence or absence of L-type Ca2+
      channel modulators. Diazepam (30 microM) and midazolam (10 microM) had no effect
      on peak [Ca2+]i of a caffeine-induced [Ca2+]i transient, which was used as a
      measure of SR Ca2+ content. CONCLUSION: Midazolam and diazepam have differential
      effects on cardiac E-C coupling. Diazepam, but not midazolam, enhances cardiac E
      C coupling independent of L-type Ca2+ channel modulation.

PMID- 16421670
TI  - Anandamide absorption by direct hemoperfusion with polymixin B-immobilized fiber
      improves the prognosis and organ failure assessment score in patients with
      sepsis.
AB  - PURPOSE: Direct hemoperfusion (DHP) with polymixin B-immobilized fiber (PMX) has
      been reported to be effective for patients with septic shock. The aim of this
      study was to clarify the mechanism of PMX-DHP effect on septic shock. METHODS:
      The following parameters were measured in septic shock patients who were treated
      with PMX-DHP: survival rate, sepsis-related organ failure assessment (SOFA)
      score, acute physiology and chronic health evaluation II (APACHE-II) score, and
      plasma concentrations of cannabinoids [anandamide (ANA) and 2-arachidonyl
      glyceride (2-AG)], cytokines [interleukin (IL)-6, IL-8, IL-10], transforming
      growth factor beta (TGF-beta), and calcitonin gene-related peptide (CGRP)]. The
      primary end point was mortality from all causes at day 28 after intensive care
      unit (ICU) admission or discharge. RESULTS: The survival rate of all patients at
      28 days after ICU admission was 37.5% (9/24). The survival group showed
      significantly lower SOFA and APACHE-II scores than the nonsurvival group after
      PMX-DHP treatment (P = 0.008 and 0.028, respectively). The improved SOFA score
      group showed a better survival rate than the nonimproved SOFA score group (71.4%
      versus 23.5%, P = 0.028). Plasma ANA level significantly decreased after PMX-DHP
      treatment both in the improved SOFA score group and in the survival group. The
      level of 2-AG, however, showed no significant change in either group. CONCLUSION:
      ANA, an intrinsic cannabinoid that induces hypotension in septic shock, is
      inferred to be the main mechanism of the PMX-DHP effect. Removal of ANA by PMX
      DHP could be key to successful septic shock treatment.

PMID- 16421672
TI  - Perioperative respiratory complications caused by cystic lung malformation in
      Proteus syndrome.
AB  - A 7-year-old girl with Proteus syndrome, complicated with severe kyphoscoliosis
      and cystic lung malformation, developed respiratory complications during and
      after posterior spinal fusion under general anesthesia. We speculated that low
      oxygenation while in the prone position contributed to ventilation perfusion
      mismatch owing to the cystic lung malformation that existed predominantly in the
      right lung, and that postoperative respiratory failure was caused by initially
      increased bronchial mucous secretions and secondary persistent bacterial
      pneumonia. Cystic lung malformation rather than reduced respiratory function,
      although both can be a cause of mucous clearance impairment, should be considered
      as one of the predictive factors for perioperative respiratory failure in Proteus
      syndrome.

PMID- 16421673
TI  - Right coronary artery spasms triggered by mechanical compression during off-pump
      coronary artery bypass grafting surgery.
AB  - In this case report, we describe recurrent spasms of the right coronary artery
      with no apparent preexisting abnormal angiogram that caused second-degree
      atrioventricular (AV) block and inferior wall hypokinesis. These hemodynamic
      changes were induced by mechanical compression of the right coronary artery by a
      pericardium drain tube. From our experience, we should be aware that mechanical
      compression may trigger an exaggerated vasomotor response, leading to severe
      coronary artery spasms.

PMID- 16421674
TI  - Prolonged relaxant effects of vecuronium in patients with deliberate
      hypermagnesemia: time for caution in cesarean section.
AB  - We present two cases showing significantly prolonged action of vecuronium from
      magnesium treatment after general anesthesia for urgent cesarean section. The
      serum magnesium levels were maintained at a therapeutic range for severe
      eclampsia in one patient (5.6 mg.dl(-1)) and for tocolysis in another with
      placenta previa totalis (6.9 mg.dl(-1)). The obstetrics-specific emergency in
      each patient led us to proceed with general anesthesia but using reduced-dose
      vecuronium, which failed to prevent prolongation of the neuromuscular block. As a
      result, the patients received prolonged mechanical ventilation. Our cases
      underscore the need for anesthesiologists as well as obstetricians to be aware of
      the prolongation of the action of nondepolarizing muscle relaxants as a result of
      magnesium treatment.

PMID- 16421675
TI  - Massive postoperative polyuria following total gastrectomy for gastric cancer.
AB  - Massive postoperative polyuria is rare, except in neurosurgery patients. Here we
      report excessive polyuria in a 59-year-old woman following total gastrectomy for
      advanced gastric cancer. The etiology of the patient's polyuria was unknown.
      Urine output was measured hourly and replaced with Ringer's lactate solution at
      80% of measured volume. The rate of urine output during 9 postoperative days
      ranged from 900 to 2700 ml.h(-1). Several administrations of an antidiuretic
      hormone (ADH) analogue were ineffective in reducing urine output, suggesting a
      possible relationship of the massive polyuria to nephrogenic diabetes insipidus.
      Following oral administration of a thiazide diuretic, known to exert an
      antidiuretic action in nephrogenic diabetes insipidus, urine output was
      dramatically reduced. We conclude that this case of massive polyuria probably
      resulted from postoperative nephrogenic diabetes insipidus.

PMID- 16421676
TI  - Intraoperative fetal heart rate monitoring during emergency neurosurgery in a
      parturient.
AB  - Malignant brain tumors during pregnancy are rare, and these patients seldom
      require immediate surgical intervention. A 27-year-old pregnant woman underwent
      emergency craniotomy. Anesthesia was induced with intravenous thiopental
      fentanyl; it was maintained with isoflurane in oxygen and continuous intravenous
      remifentanil infusion. We used full stomach precautions but omitted
      succinylcholine for fear of increasing the intracranial pressure during induction
      of anesthesia. To detect fetal hypoxia and the effects of anesthesia on fetal
      hemodynamics, the fetal heart rate (FHR) was monitored using a fetal Doppler
      ultrasonography unit fixed to the mother's abdominal wall. Intraoperative and
      recovery periods were uneventful. Use of an isoflurane and remifentanil
      combination provided stable hemodynamics with adequate arterial blood pressure to
      avoid uterine hypoperfusion and fetal hypoxia. In this case, using FHR monitoring
      we found that craniotomy can be performed safely under isoflurane/remifentanil
      based-general anesthesia during the second trimester of pregnancy.

PMID- 16421677
TI  - Effects of intravenous lidocaine prior to intubation on postoperative airway
      symptoms.
AB  - We investigated whether intravenous lidocaine prior to endotracheal intubation
      influences the postoperative airway symptoms of sore throat, cough, and sputum.
      After ethics committee approval, 80 patients undergoing elective operations were
      studied. A total of 20 patients were given lidocaine 1.0 mg.kg(-1) (group L1), 20
      patients were given lidocaine 1.5 mg.kg(-1) (group L2), and 40 patients received
      normal saline (group C). The sore throat incidence was 20% in group L1, 0 in
      group L2, and 40% in group C. Cough incidence was 0 in group L1, 20% in group L2,
      and 40% in group C. Sputum incidence was 35% in group L1, 25% in group L2, and
      47.5% in group C. There were significant differences in the incidences (P < 0.01)
      and severity (P < 0.01) of sore throat and cough in groups C and L (groups L1 +
      L2). There were no significant differences between groups in terms of the
      incidence or severity of sputum. In conclusion, intravenous lidocaine prior to
      endotracheal intubation decreased the incidence of postoperative sore throat and
      cough.

PMID- 16421678
TI  - Anesthetic management for the minimally invasive Nuss procedure in 21 patients
      with pectus excavatum.
AB  - The aim of this study was to assess the anesthetic management and postoperative
      analgesic effect of continuous epidural infusion for the minimally invasive Nuss
      procedure. A total of 21 operated cases were analyzed retrospectively.
      Thoracoscopy was used in all cases. General anesthesia with endotracheal
      intubation was induced and maintained with oxygen, air, sevoflurane, and fentanyl
      in all cases. Thoracic epidural anesthesia was performed after induction at the
      level between Th4 and 12. When the bar was placed via insertion under the
      sternum, six patients exhibited sinus tachycardia and one showed premature atrial
      contraction for 2-4 beats before recovering spontaneously within 1 min.
      Operations were uneventful. The mean operating time was 115 min and anesthetic
      time was 193 min. In X-ray findings, residual pneumothorax and pleural effusion
      were found in seven (33.3%) and eight (38.0%) patients, respectively. In all
      cases, these symptoms were resolved spontaneously within 5 days. Epidural
      fentanyl (0.3 microg.kg(-1).h(-1)) in 0.125% bupivacaine (0.15 ml.kg(-1).h(-1))
      or 0.2% ropivacaine (0.15 ml.kg(-1).h(-1)) were used for 3 days to relieve
      postoperative pain. Postoperatively, 12 (57.1%) patients required no additional
      analgesics, and 4 (19.0%) patients required a single dose of dicrofenac sodium or
      pentazocine. Although the Nuss procedure is minimally invasive, we should pay
      attention to the possibility of many intra- and postoperative complications.
      Continuous epidural infusion of fentanyl with local anesthetics provides
      effective postoperative pain relief and prevents complications such as bar
      displacement after the Nuss procedure.

PMID- 16421679
TI  - Higher preoperative D-dimer value remain high postoperatively in patients with
      rheumatoid arthritis compared with those with osteoarthrosis.
AB  - The differences in hemostatic condition between patients with inflammatory
      rheumatoid arthritis (RA) and noninflammatory osteoarthrosis (OA) were studied.
      Twenty-six patients undergoing total knee arthroplasty were enrolled. Compared
      with OA patients, RA patients showed a higher platelet count and D-dimer value
      preoperatively, and D-dimer remained high for 1 week after the operation.
      Patients with OA showed popular DD change, with the lowest value observed before
      the operation, and a gradual increase for 1 week after the operation. The highest
      value of thrombin-antithrombin complex was observed immediately after the
      operation. Fibrinogen and the clot rate at 1 week after operation were higher in
      both patient groups. We concluded that patients with RA showed different
      perioperative hemostatic change than patients with OA.

PMID- 16421681
TI  - The effect of gynecologic laparoscopy on propofol concentrations administered by
      the target-controlled infusion system.
AB  - The purpose of this study was to assess the effect of gynecologic laparoscopy on
      propofol concentrations administered by the target-controlled infusion (TCI)
      system. Thirteen patients undergoing gynecologic laparoscopy (intraabdominal
      pressure of 10 mmHg) were enrolled in this study. Anesthesia was induced with
      vecuronium 0.1 mg.kg(-1) and propofol, then maintained by 60% nitrous oxide and
      sevoflurane in oxygen and a constant infusion of propofol. Propofol was
      administered to all subjects by means of a target-controlled infusion to achieve
      propofol plasma concentration at 6.0 microg.ml(-1) at intubation and 2.0
      microg.ml(-1) after intubation. Before and during laparoscopy, plasma propofol
      concentration was determined using high-performance liquid chromatograhy. Cardiac
      output (CO) and effective liver blood flow (LBF) were also measured using
      indocyanine green as an indicator. Before and during pneumoperitoneum, there were
      no significant differences in propofol concentrations between each point.
      Propofol concentrations were well achieved to predicted concentrations
      administered by the TCI system during gynecologic laparoscopy under propofol and
      sevoflurane anesthesia.

PMID- 16421680
TI  - Dexmedetomidine during local anesthesia.
AB  - The objective of our study was to assess the efficacy and safety of
      dexmedetomidine given in a small dose for a 1-h infusion as an adjuvant to local
      analgesia in ophthalmic operations. The study was double-blind prospective,
      randomized, and placebo controlled. We studied the effects of a small dose of
      dexmedetomidine (0.5 micro.kg(-1).h(-1) for 10 min followed by 0.2 micro.kg(
      1).h(-1) for 50 min. Patients were divided randomly into two groups with 20
      patients in each: group A was the study group and group B was the placebo group.
      Heart rate, systolic blood pressure, and diastolic blood pressure were
      significantly lower in the dexmedetomidine group than the placebo group.
      Bispectral index values were significantly lower in the dexmedetomidine group
      than the placebo group. Also, intraocular pressure significantly decreased in the
      dexmedetomidine group compared to the placebo group. The study revealed that
      dexmedetomidine in the studied dose has a sedative effect, provides safe control
      of heart rate and blood pressure, and also decreases intraocular pressure during
      ophthalmic surgery under local anesthesia.

PMID- 16421683
TI  - Development of a safe guidewire.
AB  - As the result of a locking phenomenon that may occur in a guidewire inside a
      metal puncture needle when using the Seldinger technique to insert a central
      venous catheter, the guidewire can break and cause an embolism. To counter this
      possibility we devised a guidewire with a structure that made it difficult for
      locking to occur and compared it to conventional guidewires. Conventional
      guidewires are wound lengthways with a spring. The improved version has a special
      multi-ply structure. A series of 100 cases were divided into two groups: group A,
      the conventional guidewire group; and group B, the improved guidewire group. We
      punctured the internal jugular vein and attempted insertion of the guidewire
      through the side hole of a 22-gauge metal needle. We then compared the frequency
      of locking and the frequency of bending of the guidewire tips that have been
      withdrawn. In group A, locking occurred in 72% of the cases where the guidewire
      was unable to be inserted, but this figure was 0% in group B. The improved
      guidewire has the advantage of reducing the risk of locking and of guidewire
      breakage.

PMID- 16421682
TI  - Effect of propofol on ropivacaine metabolism in human liver microsomes.
AB  - A combination of the general anesthetic propofol and epidural anesthesia with a
      local anesthetic is widely used. The metabolism of ropivacaine and that of
      lidocaine are mediated by similar P450 isoforms. Previously, propofol was found
      to inhibit the metabolism of lidocaine in vitro. Here we investigated whether
      propofol inhibits the metabolism of ropivacaine using human liver microsomes in
      vitro. Ropivacaine (6.0 micromol.l(-1)) as the substrate and propofol (1-100
      micromol.l(-1)) were reacted together using human microsomes. The concentrations
      of ropivacaine and its major metabolite 2',6'-pipecoloxylidide (PPX) were
      measured using high-performance liquid chromatography. The metabolic activity of
      ropivacaine was reflected in the production of PPX. The inhibitory effects of
      propofol on ropivacaine metabolism were observed to be dose-dependent. The IC50
      of propofol was 34.9 micromol.l(-1). Propofol shows a competitive inhibitory
      effect on the metabolism of ropivacaine (i.e., PPX production mediated by CYP3A4)
      in human CYP systems in vitro.

PMID- 16421685
TI  - Tube obstruction of CobraPLA in a patient with fixed flexed neck.

PMID- 16421684
TI  - Carbon dioxide exhalation temporarily increases during electroconvulsive therapy.
AB  - Electroconvulsive therapy induces hypermetabolism and elevates oxygen and energy
      demands, while more carbon dioxide is produced than usual. The purpose of the
      present study was to determine the elevated carbon dioxide exhalation and the
      adequate ventilation volume during electroconvulsive therapy. Carbon dioxide
      exhalation during an electrically induced seizure was continuously monitored by
      capnography and spirography in 15 patients with endogenous depression. A
      laryngeal mask airway was used to measure the airway gas flow. Data were
      collected during a total of 80 electroconvulsive therapy trials. The carbon
      dioxide exhalation at 1 min after electrical stimulation was higher than the
      control value (2.8 +/- 0.4 versus 2.3 +/- 0.3 ml.min(-1).kg(-1), mean +/- SD; P <
      0.05). The ventilation volume was increased for 3 min after the electrical
      stimulation to maintain the end-tidal carbon dioxide partial pressure at 35-40
      mmHg. The results showed that increasing the ventilation volume by approximately
      20% may be necessary to compensate for the increased carbon dioxide exhalation
      during electroconvulsive therapy.

PMID- 16421686
TI  - Bispectral index monitor in anesthetic management during thyroidectomy of a
      patient with poorly controlled Graves' disease.

PMID- 16421687
TI  - Transient phlebitis induced by a bolus injection of propofol.

PMID- 16421688
TI  - Implantable rhythm management device failures and patient/physician notification:
      a simmering cauldron boils over.

PMID- 16421689
TI  - Comparison of a saline irrigated cooled-tip catheter to large electrode catheters
      with single and multiple temperature sensors for creation of large radiofrequency
      lesions.
AB  - BACKGROUND: Several catheter technologies for creating large radiofrequency (RF)
      lesions are used in clinical practice, but direct comparisons of the pathological
      lesions created by these technologies are unavailable. The purpose of this study
      was to compare the safety and efficacy of lesions created by three different
      large lesion RF ablation technologies. METHODS AND RESULTS: RF lesions were
      created in all four chambers of 15 mongrel dogs using 10 mm-tip multiple
      temperature sensor catheters, 10 mm tip single temperature sensor catheters, and
      4 mm cooled-tip catheters. Pathological lesions were bisected, and measured after
      viability staining. A total of 242 (79 large-tip single sensor, 82 large-tip
      multiple sensor, and 81 cooled-tip) lesions were created. All atrial lesions were
      transmural but tended to have larger surface areas with the single thermistor
      large-tip catheter (73.4 +/- 24.8 mm2) compared to either the multithermistor
      large-tip (60.9 +/- 28.3 mm2) or the cooled-tip (61.9 +/- 28.5 mm2) catheters (p
      = 0.07), especially those in the IVC-TA isthmus. Depths and volumes of
      ventricular lesions created by the multiple-thermistor catheter (5.0 +/- 1.5 mm;
      260 +/- 168 mm3) were smaller than either the single thermistor (5.7 +/- 1.5 mm;
      428 +/- 290 mm3) or cooled-tip (6.1 +/- 1.8 mm; 403 +/- 217 mm3) catheters (p <
      0.05). The difference in the depth and volume of lesions made by large-tip single
      thermistor and cooled-tip catheters was not significant. Char formation occurred
      during 11% of ablation with the single thermistor catheter, 6% with
      multithermistor and 8% of cooled-tip catheter (p = NS). There were no
      complications of ablation. CONCLUSIONS: All three catheters reliably created full
      thickness atrial lesions. For ventricular lesions, depths and volumes were
      similar for 10 mm-tip single thermistor and cooled-tip catheters. The
      multithermistor catheter lesions were smaller due to more precise temperature
      regulated power control. Safety was similar in all 3 groups.

PMID- 16421690
TI  - Heart rate variability: does it change after RF ablation of reentrant
      supraventricular tachycardia?
AB  - BACKGROUND: Following RF ablation of reentrant supraventricular tachycardia,
      inappropriate sinus tachycardia may occur. Local parasympathetic denervation is a
      possible mechanism for these rhythm disturbances. The purpose of this study was
      to determine the incidence of sinus tachycardia and to determine the relation
      between endocardial lesions at different ablation sites and alterations in
      autonomic tone in several different groups of patients with supraventricular
      tachycardia, using techniques of heart rate variability analysis. METHODS: The
      subjects of this study were 75 patients (48 women, 27 men) with a mean age of
      39.99 (SD = 13.39). They underwent RF ablation of AV nodal slow pathways (40
      cases), posteroseptal APs (23 cases), left lateral and right free wall APs (12
      cases) because of symptomatic tachycardias. The mean sinus rate and time domain
      (standard deviation of RR intervals and root mean square of differences of
      adjacent RR intervals) and frequency domain (low frequency, high frequency and
      low frequency/high frequency ratio) analyses of heart rate variability were
      obtained by use of 24 hour Holter monitoring before and 1 month after ablation
      compared with pre-ablation values. RESULTS: Analysis of 24 hour ambulatory Holter
      monitors, performed 1 month after RF ablation, showed no significant changes in
      time and frequency domain parameters of heart rate variability in different
      groups. A significant increase in mean heart rate was noted after RF ablation at
      AV nodal slow pathway group and left freewall/right free wall accessory pathways
      group. Patients undergoing RF ablation of right or left posteroseptal accessory
      pathways had no significant increase in the mean heart rate. CONCLUSION: In
      summary, an increase in sinus tachycardia may be initiated by RF ablation of
      atrioventricular reentrant tachycardia (AVNRT) and right free wall or left free
      wall accessory pathways. This finding shows that the modifications of heart rate
      are not directly related to the posteroseptal region or to the accessory
      pathways.

PMID- 16421691
TI  - The electrophysiologic characteristics in patients with only ventricular-pacing
      inducible slow-fast form atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) can be usually
      induced by atrial pacing or extrastimulation. However, it is less commonly
      induced only by ventricular pacing or extrastimulation. OBJECTIVE: The purpose of
      this retrospective study was to investigate the electrophysiologic
      characteristics in patients with slow-fast form AVNRT that could be induced only
      by ventricular pacing or extrastimulation. METHODS: The total population was 1497
      patients associated with AVNRT. There were 1373 (91.7%) patients who had slow
      fast form AVNRT included in our study. Group 1 (n = 45) could be induced only by
      ventricular pacing or extrastimulation, and Group 2 (n = 1328) could be induced
      by only atrial stimulation or both atrial and ventricular stimulation. The
      electrophysiologic characteristics of the group 1 and group 2 patients were
      compared. RESULTS: Group 1 patients had a significantly lower incidence of both
      antegrade and retrograde dual AV nodal pathways. The pacing cycle length (CL) of
      the antegrade 1:1 fast pathway (FP) and antegrade ERP of the FP were both
      significantly shorter in Group 1 patients. Mean antegrade FRP of the fast and
      slow pathways were significantly shorter in Group 1 patients. The differences of
      pacing CL of 1:1 antegrade conduction, antegrade ERP and FRP were much longer in
      Group 2 patients. CONCLUSION: This study demonstrated the patients with slow-fast
      form AVNRT that could be induced only by ventricular stimulation had a lower
      incidence of dual AV nodal pathways and the different electrophysiologic
      characteristics (shorter pacing CL of the antegrade 1:1 FP, antegrade ERP of the
      FP and the differences of pacing CL of 1:1 antegrade conduction, antegrade ERP
      and FRP) from the other patients. The specific electrophysiologic characteristics
      in such patients could be the reason that could be induced only by ventricular
      stimulation.

PMID- 16421692
TI  - Is dual defibrillator better than conventional DDD pacing in brady-tachy
      syndrome? Results of the ICARUS Trial (Internal Cardioversion Antitachypacing and
      Prevention: Resource Utilization Study).
AB  - AIM OF THE STUDY: To compare the impact of dual defibrillator versus conventional
      DDD pacing on quality of life and hospitalizations in patients with sinus node
      disease and recurrent symptomatic atrial fibrillation. STUDY DESIGN: Prospective,
      parallel, controlled trial. METHODS: Sixty-three patients (41 M, mean age 71 +/-
      8 years) with sinus node disease and at least three symptomatic episodes of
      atrial fibrillation during the last year were enrolled. Thirty-one consecutive
      patients received a dual defibrillator (group A) and 32 standard DDD pacing
      (group B). In group A, 12 patients received an external remote-control device in
      order to shock themselves in case of atrial fibrillation, while 19 were scheduled
      for early in-hospital manual shock. Seventy-five percent had been hospitalized
      during the last year and 57% had required electrical cardioversion. Atrial
      fibrillation was persistent in 63.5% and paroxysmal in 37.5%. The follow-up
      lasted 1 year. RESULTS: Atrial fibrillation recurred in 83.3% in group A and
      79.3% in group B (p = ns). Electrical cardioversion was applied in 54.8% in group
      A and in 21.9% in group B (p < 0.05). On the whole, 89.5% of electrical
      cardioversions were delivered in the defibrillator group (p < 0.0001). In the
      whole population 27.0% patients had cardiac-related hospitalization (31.2% in the
      pacemaker group and 22.6% in the defibrillator group, p = n.s.). In patients with
      persistent atrial fibrillation, cardiac-related hospitalization rate was
      significantly lower in the group A (0% vs. 30%, p < 0.05). Considering Symptom
      Check List, symptoms significantly improved in the whole population, but symptom
      number and frequency improved significantly only in the group A. Similarly, SF-36
      questionnaire scores showed a little higher quality of life improvement in the
      group A. CONCLUSIONS: Dual defibrillator showed consistent trends toward a higher
      effectiveness when compared with standard DDD pacing. Dual defibrillator was
      associated to reduced in-patient cardioversions and to better quality of life.
      All-cause hospitalizations were reduced only in patients with persistent atrial
      fibrillation.

PMID- 16421693
TI  - Efficacy and safety of ICD therapy in a population of elderly patients treated
      with optimal background medication.
AB  - INTRODUCTION: Implantable cardioverter-defibrillator (ICD) therapy has been shown
      to improve survival in patients with structural heart disease and at high risk
      for life threatening ventricular arrhythmias. Whether elderly patients benefit
      from device therapy in a similar way as younger patients is largely unknown.
      METHODS: We retrospectively analyzed data from 375 consecutive ICD recipients
      with structural heart disease. Patients were divided into two groups, younger
      than 70 years at time of ICD implantation (group 1) or 70 years or older (group
      2). Main outcome measures were time to death from any cause and time from first
      appropriate ICD therapy to death. RESULTS: Group 1 and 2 patients were comparable
      with respect to clinical presentation and average follow-up duration. In the
      elderly patient group, 78% received an ICD for secondary prevention versus 63% in
      group 1 (p = 0.007). During a mean follow-up period of 26.5 +/- 18.1 months,
      there was no significant difference in overall mortality among the two groups: 47
      patients died, 34 (12.5%) of group 1 versus 13 (12.7%) of group 2. The average
      time to death was 28.4 +/- 16.7 vs 30.4 +/- 22.1 months after device
      implantation, respectively (p = ns). There was no difference in time from device
      implantation to first adequate ICD therapy and time from first appropriate ICD
      therapy to death among the two groups (p = ns). Device associated complications
      were comparable in both groups. CONCLUSIONS: Elderly ICD recipients had
      comparable survival rates and appropriate use of the ICD compared to younger
      individuals.

PMID- 16421694
TI  - A new and simple method for distinguishing complete from incomplete block through
      the cavotricuspid isthmus.
AB  - BACKGROUND: A complete line of block (CLOB) in the cavotricuspid isthmus (CTI) is
      the endpoint of typical atrial flutter ablation. Before CTI block is obtained, a
      progressive CTI conduction delay due to an incomplete line of block (InLOB) can
      be difficult to distinguish from CLOB. The purpose of this study was to assess a
      new simple approach based on the changes in atrio-ventricular (AV) conduction
      delays during septal and lateral right atrial pacing, to distinguish a CLOB from
      an InLOB during typical atrial flutter (AFL) ablation. METHODS AND RESULTS: Forty
      patients who presented an InLOB before a CLOB, and a stable (AV) conduction delay
      at 600 ms cycle length pacing (when in sinus rhythm), during AFL ablation were
      included in this study. A 24-pole mapping catheter was positioned so that 2
      adjacent dipoles bracketed the targeted CTI line of block (LOB), with proximal
      dipoles lateral to the LOB and distal dipoles in the coronary sinus. Two pacing
      sites were lateral (position L1 and L2) and one was septal (position S) to the
      LOB, with locations L1 and S closest to the LOB. During L1, L2 and S site pacing,
      the delay between the pacing artefact and the peak of the R wave in a surface ECG
      (lead II) was measured. We measured the following conduction delays (mean +/- SD
      in ms), during InLOB versus CLOB: (L1 to R) 320.5 +/- 68.0 versus 367.0 +/- 62.0,
      p = 0.001; (L2 to R) 333.0 +/- 59.0 versus 338.0 +/- 62.0, p = 0.663, (S to R)
      259.4 +/- 51.5 versus 247.1 +/- 55.5, p = 0.987. We calculated the following data
      during an InLOB versus a CLOB: (L1R-L2R) -12.3 +/- 7 versus 20.2 +/- 12.7, p =
      0.001; (L1R-SR) 51.1 +/- 21.5 versus 120.1 +/- 16.6, p < 0.05. The sensitivity,
      specificity, positive and negative predictive values for CLOB with (L1R-SR > 94
      ms) and with (L1R-L2R > 0 ms) were respectively; 100%, 98%, 98% and 100%.
      CONCLUSIONS: This study establishes that lateral versus septal right atrial
      pacing sites combined with the measure of AV conduction delay on a surface ECG
      can be useful to distinguish a CLOB from an InLOB during AFL ablation.

PMID- 16421695
TI  - Assessment of ability of activation mapping by duodecapolar catheter to diagnose
      complete isthmus block utilizing electroanatomical mapping system.
AB  - Duodecapolar catheters (DPCs) have been widely used to diagnose isthmus block
      after ablation in patients with atrial flutters. The purpose of this study was to
      assess the ability of DPC to diagnose isthmus block utilizing electroanatomical
      mapping system (CARTO). METHODS: Sixty-two patients with common atrial flutter
      underwent isthmus ablation during CS pacing while DPC was positioned at lateral
      wall of RA along tricuspid annulus (TA). When activation sequence of DPC
      recording changed exclusively counter-clockwise after ablation, or did not even
      after ablations targeting single potentials on ablation line (Ab-L), only lateral
      side of Ab-L was remapped using CARTO to assess whether complete block (CB) was
      established. RESULTS: After ablation, DPC recording suggested CB and incomplete
      block (ICB) in 53 (85%) and 9 patients (15%), respectively. In 51/53 patients
      (96%) with CB suggested by DPC recordings, CARTO remap also demonstrated CB,
      however, in the remaining two patients (4%), demonstrated ICB with residual
      isthmus conduction that was slow enough to allow wavefront conducting around TA
      to arrive at distal dipole of DPC earlier, mimicking CB. In 4/9 patients (44%)
      with ICB suggested by DPC recordings, CARTO remap also demonstrated ICB, however,
      in the remaining five patients (56%), demonstrated CB with earlier arrival of
      wavefront traversing posterior wall at just lateral to Ab-L than that conducting
      around TA, mimicking ICB. Sensitivity, specificity, positive, and negative
      predictive values of DPC to diagnose CB were 91, 67, 96, and 44%, respectively.
      CONCLUSIONS: Mapping using DPC would not be sufficient for diagnosis of CB and
      ICB.

PMID- 16421696
TI  - Case report: Radiofrequency catheter ablation of typical atrial flutter and the
      atrioventricular junction via the superior vena caval approach in a patient with
      a congenital absence of an inferior vena cava.
AB  - The absence of an inferior vena cava is a rare congenital condition often without
      clinical significance. Alternative venous approaches are often needed to treat
      these patients. We report a case of successful ablation of both isthmus dependent
      flutter and the AV junction using the superior vena cava in a patient with an
      inferior vena cava anomaly.

PMID- 16421697
TI  - Berndt Luderitz (1940-present).

PMID- 16421702
TI  - Lawnmower injuries in children: a 10-year experience.
AB  - Approximately 77,800 annual lawnmower-related injuries are treated in the USA,
      with 9,300 involving children. This work reviews the literature and reports our
      10-year experience with lawnmower injuries. We retrospectively reviewed patients
      with lawnmower injuries admitted to the Women and Children's Hospital of Buffalo
      from 1995 to 2005 and reviewed the literature. Sixteen patients with mower
      related injuries were admitted to our institution, with three due to walk-behind
      mowers and 13 due to riding mowers. The mean age was 7.5 years. Riding mower
      injuries had a higher average injury severity score (14.3 vs. 9) and a longer
      average length of hospital stay (15 vs. 2 days). All of the walk-behind mower
      injuries were extremity injuries, with two requiring amputations. Eleven of the
      riding mower injuries had extremity injuries alone, one had isolated torso
      injuries, and one had both extremity and torso injuries. Three required
      amputations, and the two patients with torso injuries required extensive surgical
      reconstructions. Pediatric lawnmower injuries, particularly due to riding mowers,
      are a highly preventable cause of morbidity and mortality. Increased public
      safety awareness and further manufacturer safety modifications should be strongly
      encouraged in order to limit this cause of pediatric trauma.

PMID- 16421703
TI  - Hypertension in a cohort of African children with renal tumours.
AB  - Hypertension is a frequent problem in children with renal tumour, yet there are
      few reports from centres in the third world. A retrospective study of blood
      pressure in a cohort of 46 patients with renal tumours seen over a 3-year period
      was carried out. Fifty percent of patients presenting with Wilms' tumour were
      hypertensive. Serum concentrations of active renin correlated poorly with blood
      pressure. There was no correlation between serum concentrations of active renin
      and tumour mass or histology. Specific antihypertensive therapy was offered to 11
      patients who had either neurological or cardiac complications of hypertension.
      All other patients with Wilms' tumour had their blood pressure controlled by
      neoadjuvant chemotherapy. Patients with mesoblastic nephroma were managed by
      primary surgery. Patients with asymptomatic hypertension may be monitored as
      hypertension will resolve with neoadjuvant chemotherapy. Those with compelling
      symptomatology will require additional hypertensive medication.

PMID- 16421704
TI  - [Epithelioid hemangioendothelioma of the lung (IVBAT)--clinicopathological and
      immunohistochemical analysis of 11 cases].
AB  - Epithelioid hemangioendothelioma (EHE) of the lungs (syn.: intravascular
      bronchioloalveolar tumor/IVBAT) is a neoplasm with a vascular line of
      differentiation. This study provides a clinicopathological analysis of 11 cases
      of this tumor. There were 7 female and 4 male patients. Patients' age ranged from
      33 to 83 years (mean: 49.8, median: 48 years) showing 2 peaks (third/fourth and
      sixth/eighth decades). The typical radiological appearance revealed multiple
      bilateral lung nodules from 0.5 to 2 cm. In 2 cases, a striking perivascular and
      intravascular growth pattern associated to pulmonary veins was evident. All
      tumors were characterized by epithelioid tumor cells with nests, cords and
      strands embedded in a sclerosing, hyaline matrix with alveolar, bronchiolar and
      vascular extension. Necrosis was identified in 8 tumors and ossification in 2
      tumors. The mitotic index was below one mitosis in 10 HPF. By
      immunohistochemistry, all tumors were positive for CD 31, CD 34, and vimentin,
      60% positive for factor VIII, and negative for pancytokeratin and calretinin.
      Follow-up was available for 8 patients with a range of 6 to 105 months (mean:
      51.5 months, median: 52 months): 3 patients died (2 certainly from their tumors),
      4 are alive disease-free, and one is alive with metastases. EHE of the lungs
      (IVBAT) represents an intermediate-grade, malignant, mesenchymal neoplasm with a
      characteristic histological appearance and immunohistochemical profile.

PMID- 16421705
TI  - [Hematological side effects of tyrosine kinase inhibition using imatinib].
AB  - Imatinib (STI571, Gleevec/Glivec) and other small-molecule tyrosine kinase
      inhibitors are highly effective in the treatment of chronic myeloid leukemia
      (CML), gastrointestinal stromal tumors and, for example, eosinophilia-associated
      chronic myeloproliferative disorders. This molecularly targeted approach disrupts
      abnormal tyrosine kinase dependent signalling pathways, thus providing a
      preferred treatment option for selected neoplastic disorders with activating
      mutations of Abelson-, Abl-related-, Kit-, and platelet-derived growth factor
      receptor A and B genes. Loss of response to imatinib may be due to an acquired
      resistance of emerging mutant tumor cell clones. Therapy is generally well
      tolerated. However, toxicities including edema, skin rashes, fatigue, nausea and
      myelosuppression have been reported. Philadelphia/Bcr-Abl-negative clonal
      chromosomal abnormalities may develop. Bone marrow trephines obtained from CML
      patients in complete remission with prolonged pancytopenia secondary to imatinib
      generally show marrow hypoplasia. Morphological features may be in keeping with
      either aplastic anemia or myelodysplasia developing in Philadelphia-negative
      hematopoiesis. Single or multilineage myelodysplasia may be accompanied by an
      excess of blasts and rarely evolves into acute leukemia in CML patients. Severe
      adverse hematological effects of imatinib are extremely rare. Current questions
      involve the molecular mechanisms of hematological side effects of tyrosine kinase
      inhibitors with special regard to the emergence of distinct aberrant clones.

PMID- 16421707
TI  - [Long-lasting, refractory headache after bilateral dissection of the internal
      carotid artery].
AB  - Headache is usually the first and the most frequent symptom of cervicocephalic
      arterial dissection. Besides headache ipsilateral Horner's syndrome, cranial
      nerve palsies, or pulsatile tinnitus are observed. Serious complications of
      arterial dissection are ischemic strokes, which mostly occur later in the course
      of time. We report on a patient with spontaneous bilateral carotid artery
      dissection, who suffered from atypically prolonged, severe, and refractory
      headache. High-dose administration of nonsteroidal anti-inflammatory drugs as
      well as opioids were ineffective. Pain relief was only achieved after a 3-day
      course of corticosteroids (100 mg methylprednisolone/day).

PMID- 16421706
TI  - [Analgesia in pediatric outpatient surgery].
AB  - A number of surgical procedures for pediatric patients can be suitably performed
      in an outpatient setting. The advantages are impressive: reduced costs, lower
      rate of infection, avoidance of hospitalization with the inherent psychological
      stress, and timely return of the patients to their familiar home environment. An
      essential feature of the quality of outpatient surgery is the efficacy of the
      perioperative pain therapy for which a multimodal approach has proven to be very
      effective: workflow tailored to children's needs, ambiance appropriate for
      children, and pharmacological analgesia. In the preliminary counseling session it
      is imperative that parents and children receive detailed information on
      procedures (role playing, modeling). Associated unpleasant factors prior to
      induction of anesthesia should be avoided. The primary element of pharmacological
      analgesia is regional anesthesia; additional options are paracetamol,
      nonsteroidal antirheumatic agents (be aware of the highest dosages!), and
      opioids. When opioids are employed, care should be taken that monitoring
      standards in the recovery room are not lowered and include pulsoxymetry. Because
      of the clearly elevated rate of postoperative nausea and vomiting related to
      perioperative administration of opioids, the lower dosage level should be chosen.
      This article presents concepts of perioperative analgesia.

PMID- 16421708
TI  - [Practical pain control in pediatric oncology. Recommendations of the German
      Society of Pediatric Oncology and Hematology, the German Association for the
      Study of Pain, the German Society of Palliative Care, and the Vodafone Institute
      of Children's Pain Therapy and Palliative Care].
AB  - In pediatric oncology, optimal pain control is still a challenge. A structured
      pain history and the regular scoring of pain intensity using age-adapted
      measuring tools are hallmarks of optimal pain control. Psychological measures are
      as important as drug therapy in the prophylaxis or control of pain, especially
      when performing invasive procedures. Pain control is oriented toward the WHO
      multistep therapeutic schedule. On no account should the pediatric patient have
      to climb up the "analgesic ladder" - strong pain requires the primary use of
      strong opioids. Give opioids preferably by the oral route and by the clock -
      short-acting opioids should be used to treat breakthrough pain. Alternatives are
      i.v. infusion, patient-controlled analgesia, and transdermal applications.
      Constipation is the adverse effect most often seen with (oral) opioid therapy.
      Adverse effects should be anticipated, and prophylactic treatment should be given
      consistently. The assistance of pediatric nurses is of the utmost importance in
      pediatric pain control. Nurses deliver the basis for rational and effective pain
      control by scoring pain intensity and documenting drug administration as well as
      adverse effects. The nurses' task is also to prepare the patient for and monitor
      the patient during painful procedures. It is the responsibility of both nurse and
      doctor to guarantee emergency intervention during sedation whenever needed. In
      our guideline we comment on drug selection and dosage, pain measurement tools,
      and documentation tools for the purpose of pain control. Those tools may be
      easily integrated into daily routine.

PMID- 16421709
TI  - [Nomograms for the improvement of refractive outcomes].
AB  - BACKGROUND: Nomograms are efficient tools to improve the predictability of
      refractive procedures by using statistical methods to analyze pre- and
      postoperative refractive data. The purpose of this work was to analyze the
      clinical relevance and limitations of nomograms in a case series. METHODS:
      Computer simulations based on the known unpredictability for refractive outcomes
      were performed for three different distribution functions of the preoperative
      refractions. In addition, the clinical applicability was investigated in three
      different cohorts that underwent laser in situ keratomileusis (LASIK). RESULTS:
      The use of individual nomograms significantly improves the predictability of the
      refractive outcome. However, theoretical investigation demonstrates that a
      homogeneous data distribution within cohorts is a key factor for predictable
      nomogram calculations. Outliers within the cohorts are not integrated into the
      nomogram calculation due to the mathematical model used. CONCLUSIONS: Nomograms
      are helpful for improving refractive outcomes. However, they are currently
      limited to approximately 90% within +/-0.5 D.

PMID- 16421710
TI  - Accurate determination of allelic frequencies in mitochondrial DNA mixtures by
      electrospray ionization time-of-flight mass spectrometry.
AB  - The mitochondrial locus 16519T/C was used as a model for the evaluation of the
      benefits of ion-pair reversed-phase high-performance liquid chromatography on
      line hyphenated to electrospray ionization time-of-flight mass spectrometry
      (ICEMS assay) for the determination of allelic frequencies of single nucleotide
      polymorphisms. This marker has gained interest in forensic science owing to its
      ability to increase the discrimination power of mitochondrial DNA testing as a
      consequence of its high variability across various populations. In a first set of
      experiments, artificial mitochondrial DNA mixtures prepared from all four
      theoretically possible 16519 alleles served as samples. Any allele occurring at a
      frequency of as low as 1-5% was unequivocally detectable irrespective of the kind
      of allelic mixture. Measured and expected allelic frequencies correlated well
      following correction of observed experimental bias, which was most probably
      attributable to differential PCR amplification and/or preferential ionization.
      For thirteen different T/C mixtures with C contents in the range 1.0-99.0%, an
      average error of 1.2% and a maximum error of 2.2% were observed. Furthermore,
      ICEMS was applied to the quantitative genotyping of eight selected individuals of
      which four were heteroplasmic with C contents in the range 1.9-34.1%. To check
      the reliability of these results, allelic proportions were additionally
      determined by a cloning assay. The results of the two assays correlated well (R
      (2)=0.9971). In all cases, deviations were obtained that were smaller than 5.4%.
      The overall observed assay performance suggests that the described mass
      spectrometric technique represents one of the most powerful assays for the
      determination of allelic frequencies available today.

PMID- 16421711
TI  - A facile method for coding and labeling assays on polystyrene beads with
      differently colored luminescent nanocrystals.
AB  - The present paper describes a new, facile and fast technique that can be used to
      incorporate CdSe/ZnS core/shell nanocrystals into polystyrene beads. The
      nanocrystals were immobilized within the polymer beads by demixing two
      nonmiscible solvents. The resulting beads were bright, homogeneously coded, and
      did not show any surface texture or photobleaching under application-relevant
      conditions. The beads were subsequently used on a model streptavidin-biotin
      binding system in order to demonstrate the applicability of the technique to
      enzyme-linked assays and multiplexing applications.

PMID- 16421712
TI  - Multiplexed SNP genotyping using nanobarcode particle technology.
AB  - Single-nucleotide polymorphisms (SNP) are the most common form of sequence
      variation in the human genome. Large-scale studies demand high-throughput SNP
      genotyping platforms. Here we demonstrate the potential of encoded nanowires for
      use in a particles-based universal array for high-throughput SNP genotyping. The
      particles are encoded sub-micron metallic nanorods manufactured by electroplating
      inert metals such as gold and silver into templates and releasing the resulting
      striped nanoparticles. The power of this technology is that the particles are
      intrinsically encoded by virtue of the different reflectivity of adjacent metal
      stripes, enabling the generation of many thousands of unique encoded substrates.
      Using SNP found within the cytochrome P450 gene family, and a universal short
      oligonucleotide ligation strategy, we have demonstrated the simultaneous
      genotyping of 15 SNP; a format requiring discrimination of 30 encoded nanowires
      (one per allele). To demonstrate applicability to real-world applications, 160
      genotypes were determined from multiplex PCR products from 20 genomic DNA
      samples.

PMID- 16421713
TI  - Mangafodipir trisodium-enhanced MR imaging of pancreatic disease.
AB  - Our study aimed to assess the diagnostic capabilities of mangafodipir trisodium
      enhanced MRI for the evaluation of pancreatic disease. Sixty-three patients
      suspected of having pancreatic disease underwent MRI with a 1.5-T device. After
      the acquisition of axial and coronal T2-weighted sequences, the MR protocol
      included T1-weighted fat-suppressed breath-hold SPGR images obtained before and
      30 min after the infusion of Mn-DPDP (Teslascan). The detection of a focal
      pancreatic lesion and its intensity were evaluated in consensus by two observers,
      who also attempted to characterize each lesion as benign or malignant. The
      reviewers were blinded to patient identification and all clinical, laboratory and
      previous imaging findings. MR imaging results were correlated with surgery
      (n=37), laparoscopy (n=1), biopsy (n=2) and imaging follow-up (n=22). Sixty-two
      subjects were effectively included in our analysis because one patient was lost
      to follow-up; final malignant and benign diagnoses were determined in 22 (35%)
      and 29 (47%) of the patients, respectively. The level of confidence in the
      diagnosis of the pancreatic lesion was significantly increased by the
      administration of Mn-DPDP as demonstrated by ROC analysis of unenhanced and post
      contrast image sets (P=0.009). Overall, on the basis of observers' readings, MR
      assessment of pancreatic disease resulted in 57 correct diagnoses (accuracy, 92%)
      and five (8%) incorrect diagnoses. The sensitivity, specificity, positive
      predictive value and negative predictive value of the reviewers for the detection
      of pancreatic lesions and for the differentiation between benign and malignant
      masses were 91% (95% CI: 84 and 98%), 93% (95% CI: 86 and 99%), 87% (95% CI: 79
      and 95%) and 95% (95% CI: 89 and 100%), respectively. Mn-DPDP-enhanced MRI is an
      effective diagnostic tool for evaluating pancreatic disease.

PMID- 16421714
TI  - Hand-arm vibration exposure of dentists.
AB  - OBJECTIVES: The use of dental handpieces exposes the dental personnel to high
      frequency vibration. Dentists have been shown to have a high frequency of finger
      related and other upper limb symptoms and a high prevalence of osteoarthrosis in
      the distal interphalangeal joints. METHODS: The vibration of 22 dental handpieces
      was measured during normal work with accelerometer. The weighted vibration
      according to the standard ISO 5349-1 and the total acceleration of high frequency
      vibration ("ultravibration") in the frequency range of 1.6-10 kHz were analyzed.
      In order to compare non-contact vibration measurement method for dental
      handpieces, vibration of 12 handpieces was measured during idling with Portable
      Digital Vibrometer and simultaneously with the accelerometer. A group of 295
      female dentists aged 45-63 years responded to a questionnaire on working
      conditions, lifestyle, and health. RESULTS: The vibration measurements of air
      turbine and micromotor handpieces showed that daily vibration exposure of
      dentists was below the exposure action value of the Vibration Directive of
      European Union. The highest vibration levels of the handpieces exist in the
      frequency range above 1,250 Hz. The traditional method and the laser method gave
      highly similar values. A long work history in dental filling and root treatment
      as well as high BMI seem to be associated with frequent finger symptoms perceived
      as vibration-related by the dentists. CONCLUSIONS: The vibration exposure of
      dentists is low determined according to European legislation. However, a long
      work history in dental filling and root treatment seems to be associated with the
      risk of frequent finger symptoms of dentists. Therefore, when "pinch-gripping" is
      used, the effects of vibration on fingers should be comprehensively studied.

PMID- 16421715
TI  - Increase in exhaled nitric oxide (eNO) after work-related isocyanate exposure.
AB  - The objective of this study was to evaluate the role of eNO changes post
      inhalative isocyanate challenge tests (DeltaeNO) with regard to specific
      asthmatic reactions and unspecific bronchial hyperresponsiveness (BHR) to predict
      clinical and subclinical responses of isocyanate workers. METHODS: 55 workers
      with isocyanate-related respiratory complaints (29 with BHR and 25 without BHR)
      underwent occupational-type challenge tests. We determined eNO before, during and
      up to 22 h after diagnostic isocyanate challenge. RESULTS: The 12 asthmatic
      responders (22%) in the isocyanate-challenge test showed the highest eNO changes
      22 h after challenge as well as a significant association between these changes
      and BHR. There was a positive association between an eNO increase of > 50% and an
      asthmatic response when compared to nonresponders with an odds ratio of 6.1; 95%
      CI 1.4-26.3; P = 0.02. More than half of the employees with BHR (52%) but only
      20% of those without BHR developed an eNO rise of > 50% after 22 h. Furthermore,
      a significant positive association was found between the combination of BHR plus
      eNO increase of 50% after 22 h and the maximum sRaw change (% of baseline value)
      during the period 0-22 h after isocyanate exposure. The combination of BHR and
      eNO increase of > 50% was also associated with clinical symptoms during specific
      challenge tests (cough, shortness of breath, and/or rhinitis). DISCUSSION AND
      CONCLUSIONS: An eNO increase 22 h post isocyanate challenge occurred in two
      thirds of responders and in approximately half of nonresponders with BHR but only
      rarely in those without BHR. The combination of BHR and eNO increase in
      nonresponders may offer a new diagnostic tool to register subjects with an
      increased risk of developing occupational asthma. However, a large study group to
      perform follow-up investigations into this topic would be helpful to emphasize
      the importance of this finding.

PMID- 16421716
TI  - Potential of Rhodococcus strains for biotechnological vanillin production from
      ferulic acid and eugenol.
AB  - The potential of two Rhodococcus strains for biotechnological vanillin production
      from ferulic acid and eugenol was investigated. Genome sequence data of
      Rhodococcus sp. I24 suggested a coenzyme A-dependent, non-beta-oxidative pathway
      for ferulic acid bioconversion, which involves feruloyl-CoA synthetase (Fcs),
      enoyl-CoA hydratase/aldolase (Ech), and vanillin dehydrogenase (Vdh). This
      pathway was proven for Rhodococcus opacus PD630 by physiological characterization
      of knockout mutants. However, expression and functional characterization of
      corresponding structural genes from I24 suggested that degradation of ferulic
      acid in this strain proceeds via a beta-oxidative pathway. The vanillin precursor
      eugenol facilitated growth of I24 but not of PD630. Coniferyl aldehyde was an
      intermediate of eugenol degradation by I24. Since the genome sequence of I24 is
      devoid of eugenol hydroxylase homologous genes (ehyAB), eugenol bioconversion is
      most probably initiated by a new step in this bacterium. To establish eugenol
      bioconversion in PD630, the vanillyl alcohol oxidase gene (vaoA) from Penicillium
      simplicissimum CBS 170.90 was expressed in PD630 together with coniferyl alcohol
      dehydrogenase (calA) and coniferyl aldehyde dehydrogenase (calB) genes from
      Pseudomonas sp. HR199. The recombinant strain converted eugenol to ferulic acid.
      The obtained data suggest that genetically engineered strains of I24 and PD630
      are suitable candidates for vanillin production from eugenol.

PMID- 16421717
TI  - A recombinant Escherichia coli whole cell biocatalyst harboring a cytochrome
      P450cam monooxygenase system coupled with enzymatic cofactor regeneration.
AB  - A cytochrome P450cam monooxygenase (P450cam) system from the soil bacterium
      Pseudomonas putida requires electron transfer among three different proteins and
      a cofactor, nicotinamide adenine dinucleotide (NADH), for oxygenation of its
      natural substrate, camphor. Herein, we report a facile way to significantly
      enhance the catalytic efficiency of the P450cam system by the coupling of its
      native electron transfer system with enzymatic NADH regeneration catalyzed by
      glycerol dehydrogenase (GLD) in Escherichia coli whole cell biocatalysts.
      Recombinant E. coli harboring the P450cam system, but lacking GLD, exhibited
      little activity for camphor hydroxylation. In contrast, coexpression of GLD with
      the proteinaceous electron transfer components of P450cam resulted in about
      tenfold improvement in the substrate conversion, implying that the whole cell
      biocatalyst utilized molecular oxygen, endogenous NADH, and glycerol in the cell
      for catalysis. The addition of glycerol to the reaction media further promoted
      camphor hydroxylation, suggesting that exogenous glycerol is also available for
      GLD in the host cell and actively participates in the catalytic cycle. These
      results clearly show the utility of GLD towards functional reconstruction of the
      native P450cam system. The present approach may also be useful for E. coli whole
      cell biocatalysts with the other NADH-dependent oxygenases and oxidoreductases.

PMID- 16421718
TI  - Perspectives for synthesis and production of polyurethanes and related polymers
      by enzymes directed toward green and sustainable chemistry.
AB  - Enzyme-catalyzed polymerization and degradation will play an important role in
      both the synthesis and chemical recycling of green and sustainable polyurethane.
      This minireview covers the new synthetic routes to polyurethane without using
      diisocyanate, the biodegradation of polyurethane, and the enzymatic synthesis and
      the chemical recycling of poly(ester-urethane) (PEU) and poly(carbonate-urethane)
      (PCU). The lipase-catalyzed polymerization of low molecular weight and
      biodegradable urethanediols with short-chain dialkyl carbonate and alkanedioates
      produced PCU and PEU, respectively. They were readily degraded in an organic
      solvent into the repolymerizable cyclic oligomers by lipase as a novel chemical
      recycling. These results will be applicable for the production strategies of
      green and sustainable polyurethanes.

PMID- 16421720
TI  - Predicting the efficiencies of 2-mercaptobenzothiazole collectors used as
      chelating agents in flotation processes: a density-functional study.
AB  - In recent years, several new chelating reagents have been synthesized and tested
      for their collecting power in sulfide and non-sulfide minerals flotation. Many
      researchers have indicated that chelating reagents have the advantage of offering
      better selectivity and specificity as flotation collectors. Therefore, density
      functional theory (DFT) calculations at the B3LYP/6-31G(d,p) level were performed
      to investigate the observed activities of 2-mercaptobenzothiazole, 6-methyl-2
      mercaptobenzothiazole and 6-methoxy-2-mercaptobenzothiazole as the most popular
      flotation collectors. The molecular properties and activity relationships were
      determined by the HOMO localizations, the HOMO energies, Mulliken charges and the
      electrostatic potentials at the thioamide functional group, which is the key site
      in the forming efficiency of the collectors studied. It is concluded that these
      quantities can be used successfully for understanding the collecting abilities of
      2-mercaptobenzothiazoles. The results obtained theoretically are consistent with
      the experimental data reported in the literature.

PMID- 16421719
TI  - Expression of the cationic antimicrobial peptide lactoferricin fused with the
      anionic peptide in Escherichia coli.
AB  - Direct expression of lactoferricin, an antimicrobial peptide, is lethal to
      Escherichia coli. For the efficient production of lactoferricin in E. coli, we
      developed an expression system in which the gene for the lysine- and arginine
      rich cationic lactoferricin was fused to an anionic peptide gene to neutralize
      the basic property of lactoferricin, and successfully overexpressed the
      concatemeric fusion gene in E. coli. The lactoferricin gene was linked to a
      modified magainin intervening sequence gene by a recombinational polymerase chain
      reaction, thus producing an acidic peptide-lactoferricin fusion gene. The
      monomeric acidic peptide-lactoferricin fusion gene was multimerized and expressed
      in E. coli BL21(DE3) upon induction with isopropyl-beta-D-thiogalactopyranoside.
      The expression levels of the fusion peptide reached the maximum at the tetramer,
      while further increases in the copy number of the fusion gene substantially
      reduced the peptide expression level. The fusion peptides were isolated and
      cleaved to generate the separate lactoferricin and acidic peptide. About 60 mg of
      pure recombinant lactoferricin was obtained from 1 L of E. coli culture. The
      purified recombinant lactoferricin was found to have a molecular weight similar
      to that of chemically synthesized lactoferricin. The recombinant lactoferricin
      showed antimicrobial activity and disrupted bacterial membrane permeability, as
      the native lactoferricin peptide does.

PMID- 16421721
TI  - A radial-distribution-function approach for predicting rodent carcinogenicity.
AB  - Carcinogenic activity has been investigated using the Radial-Distribution
      Function (RDF) approach. A discriminant model was developed to predict the
      carcinogenic and non-carcinogenic activity on a data set of 188 compounds. The
      percentage of overall classification was 76.4% for the carcinogenic chemicals and
      72.5% for the non-carcinogenic chemicals. The predictive power of the model was
      validated by two tests: a cross-validation by the resubstitution technique and a
      test set (compounds not used in the development of the model) with 79.3 and 72.5%
      good classification, respectively. The RDF descriptors were compared with eight
      other methodologies; Constitutional, Molecular walks counts, Galvez topological
      charge indices, 2D autocorrelations, Randic molecular profiles, Geometrical, 3D
      MORSE, and WHIM, demonstrating that the RDF descriptors are better to the rest of
      the approaches used.

PMID- 16421722
TI  - ESTDAB: a collection of immunologically characterised melanoma cell lines and
      searchable databank.
AB  - Cancer immunologists working in humans often require panels of tumour cell lines
      expressing different combinations of HLA alleles and other characteristics.
      Sources of cell lines are usually large cell banks carrying little
      immunologically relevant information on the available cells and limited numbers
      of different lines from the same type of tumour. Access to cells with desired
      combinations of characteristics is, therefore, difficult. Here, we describe an
      interactive database of a large collection of melanoma cell lines which have been
      extensively characterised for HLA genotype and surface expression, oncogene and
      tumour antigen expression, cytokine secretion, surface molecule expression,
      adhesion to extracellular matrix components, cytokine gene polymorphisms and
      other factors of interest to immunologists. This enables investigators to search
      for cells with particular constellations of HLA alleles, tumour antigens, etc.,
      and then request these from the cell bank. This European Searchable Tumour Cell
      Line and Data Bank (ESTDAB) was established as a Research Infrastructure of the
      European Commission. For access to the databank and further details, please go to
      http://www.ebi.ac.uk/ipd/estdab/ .

PMID- 16421723
TI  - Mycoplasma pneumoniae infection complicated by necrotizing pneumonitis with
      massive pleural effusion.

PMID- 16421724
TI  - A survey of consultant practice: intravenous salbutamol or aminophylline for
      acute severe childhood asthma and awareness of potential hypokalaemia.
AB  - British Thoracic Society guidelines recommend intravenous salbutamol or
      aminophylline for acute severe asthma in children. In the survey reported here,
      133 consultant paediatricians completed a questionnaire aimed at evaluating their
      choice of intravenous bronchodilator for acute severe asthma and their awareness
      of subsequent hypokalaemia. Of the non-Paediatric Intensive Care Unit (PICU)
      consultants who responded, 82%, including respiratory paediatricians, reported
      using aminophylline; in contrast, PICU consultants were significantly more likely
      to use salbutamol (p=<0.001). There was a lack of awareness that hypokalaemia
      occurs with aminophylline: 50% of the consultants suggested that hypokalaemia was
      rare or did not occur. Consultants using intravenous aminophylline were
      significantly less likely to recheck serum potassium levels than those using
      intravenous salbutamol (p=0.03). Based on the completed questionnaires,
      salbutamol infusions are rarely used outside the PICU, and the awareness of
      potential hypokalaemia following intravenous bronchodilator treatment is
      variable. It would appear, therefore, that standardised clinical practice is
      required in order to recognise and treat potential hypokalaemia.

PMID- 16421725
TI  - The receptor for erythropoietin is present on cutaneous mast cells.
AB  - Skin samples from patients with extra-mammary Paget disease, Bowen's disease,
      atopic dermatitis, psoriasis and non-lesional skin of nevus pigmentosus were
      immunohistochemically examined with an anti-soluble erythropoietin receptor
      antibody (anti-sEPOR antibody), and only the dermal mast cells positively stained
      in all skin samples were examined. These positively stained dermal cells were
      proved to be mast cells by double staining with anti-sEPOR antibody and either
      with anti-bikunin antibody or anti-tryptase antibody. Immunoelectron
      microscopically these EPOR were found in the secretory granules of the dermal
      mast cells. Further, EPOR in the mast cells may be consisting of only the
      extracellular domain of erythropoietin receptor molecule as the mast cells were
      immunohistochemically not reacted with an antibody to the C-terminal peptide of
      EPOR. Human mast cell line, HMC-1 cells has immunohistochemically the
      erythropoietin receptor, which was consisting of a 43 kDa major protein and a 20
      kDa minor protein in the immunoelectrophoresis. These data may indicate that EPOR
      in the mast cells may not be the whole molecule, but probably the soluble one of
      EPOR.

PMID- 16421726
TI  - Kinetic and spectroscopic characterization of the E134A- and E134D-altered dapE
      encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Haemophilus
      influenzae.
AB  - Glutamate-134 (E134) is proposed to act as the general acid/base during the
      hydrolysis reaction catalyzed by the dapE-encoded N-succinyl-L,L-diaminopimelic
      acid desuccinylase (DapE) from Haemophilus influenzae. To date, no direct
      evidence has been reported for the role of E134 during catalytic turnover by
      DapE. In order to elucidate the catalytic role of E134, altered DapE enzymes were
      prepared in which E134 was substituted with an alanine and an aspartate residue.
      The Michaelis constant (K (m)) does not change upon substitution with aspartate
      but the rate of the reaction changes drastically in the following order:
      glutamate (100% activity), aspartate (0.09%), and alanine (0%). Examination of
      the pH dependence of the kinetic constants k (cat) and K (m) for E134D-DapE
      revealed ionizations at pH 6.4, 7.4, and approximately 9.7. Isothermal titration
      calorimetry experiments revealed a significant weakening in metal K (d) values of
      E134D-DapE. D134 and A134 perturb the second divalent metal binding site
      significantly more than the first, but both altered enzymes can still bind two
      divalent metal ions. Structural perturbations of the dinuclear active site of
      DapE were also examined for two E134-substituted forms, namely E134D-DapE and
      E134A-DapE, by UV-vis and electron paramagnetic resonance (EPR) spectroscopy. UV
      vis spectroscopy of Co(II)-substituted E134D-DapE and E134A-DapE did not reveal
      any significant changes in the electronic absorption spectra, suggesting that
      both Co(II) ions in E134D-DapE and E134A-DapE reside in distorted trigonal
      bipyramidal coordination geometries. EPR spectra of [Co_(E134D-DapE)] and
      [Co_(E1341A-DapE] are similar to those observed for [CoCo(DapE)] and somewhat
      similar to the spectrum of [Co(H(2)O)(6)](2+) which typically exhibit E/D values
      of approximately 0.1. Computer simulation returned an axial g-tensor with g
      ((x,y))=2.24 and E/D=0.07; g ( z ) was only poorly determined, but was estimated
      as 2.5-2.6. Upon the addition of a second Co(II) ion to [Co_(E134D-DapE)] and
      [Co_(E134A-DapE)], a broad axial signal was observed; however, no signals were
      observed with B (0)||B (1) ("parallel mode"). On the basis of these data, E134 is
      intrinsically involved in the hydrolysis reaction catalyzed by DapE and likely
      plays the role of a general acid and base.

PMID- 16421727
TI  - Grade of bone marrow fibrosis is associated with relevant hematological findings
      a clinicopathological study on 865 patients with chronic idiopathic
      myelofibrosis.
AB  - Controversy continues to exist regarding not only the exact definition and
      grading of myelofibrosis (MF), but also whether, and to what extent, this feature
      may be correlated with clinical findings. A retrospective study was performed
      involving 865 bone marrow (BM) biopsies together with the clinical records from
      patients with chronic idiopathic myelofibrosis (CIMF). Diagnosis was established
      according to the World Health Organization criteria, and assessment of MF
      followed a consensus scoring system that included four grades (MF-0 to MF-3).
      Histopathological and clinical evaluations were carried out in an independent
      fashion. Prefibrotic and early CIMF (MF-0/-1) were presented by 565 patients
      showing borderline to mild anemia and no or slight splenomegaly, but frequently,
      thrombocytosis exceeding 500x10(9)/l was shown. In 300 patients, manifest
      reticulin and collagen fibrosis (MF-2/-3) were characterized by marked anemia,
      gross splenomegaly, peripheral blasts, and normal to decreased platelet and
      leukocyte counts. The latter cohort was consistent with findings generally in
      keeping with MF with myeloid metaplasia. Regarding the stepwise evolution of
      disease, sequential BM examinations showed that in 103 patients, prefibrotic and
      early CIMF transformed into advanced stages accompanied by correspondingly
      developing clinical and histomorphological features. Survival analysis
      (univariate calculation) revealed a significantly more favorable prognosis in
      prefibrotic vs advanced stages of CIMF. On the other hand, higher classes of MF
      also exerted a higher clinical risk profile (Lille score). In conclusion, the
      dynamics of the disease process in CIMF are characterized by evolving MF in the
      BM and closely associated changes of relevant hematological findings.

PMID- 16421728
TI  - Control of adaptive locomotion: effect of visual obstruction and visual cues in
      the environment.
AB  - Visual information regarding obstacle position and size is used for planning and
      controlling adaptive gait. However, the manner in which visual cues in the
      environment are used in the control of gait is not fully known. This research
      examined the effect of obstacle position cues on the lead and trail limb
      trajectories during obstacle avoidance with and without visual information of the
      lower limbs and obstacle (termed visual exproprioception). Eight subjects stepped
      over obstacles under four visual conditions: full vision without obstacle
      position cues, full vision with position cues, goggles without position cues and
      goggles with position cues. Goggles obstructed visual exproprioception of the
      lower limbs and the obstacle. Position cues (2 m tall) were placed beside the
      obstacle to provide visual cues regarding obstacle position. Obstacle heights
      were 2, 10, 20 and 30 cm. When wearing goggles and without position cues, a
      majority of the dependent measures (horizontal distance, toe clearance and lead
      stride length) increased for the 10, 20 and 30 cm obstacles. Therefore lower limb
      obstacle visual exproprioception was important for the control of both limbs,
      even though with normal vision the trail limb was not visible during obstacle
      clearance. When wearing goggles, the presence of position cues, which provided on
      line visual exproprioception of the self relative to the obstacle position in the
      anterior-posterior direction, returned lead and trail foot placements to full
      vision values. Lead toe clearance was not affected by the position cues, trail
      clearance decreased but was greater than values observed during full vision.
      Therefore, visual exproprioception of obstacle location, provided by visual cues
      in the environment, was more relevant than visual exproprioception of the lower
      limbs for controlling lead and trail foot placement.

PMID- 16421729
TI  - Polysynaptic inputs to vestibular efferent neurons as revealed by viral
      transneuronal tracing.
AB  - The Bartha strain of the alpha-herpes pseudorabies virus (PrV) was used as a
      retrograde transneuronal tracer to map synaptic inputs to the vestibular efferent
      neurons of the Mongolian gerbil, Meriones unguiculatus. Although previous
      experiments have shown that vestibular efferent neurons respond to visual motion
      and somatosensory stimuli, the anatomic connections mediating those responses are
      unknown. PrV was injected unilaterally into the horizontal semicircular canal
      neuroepithelium of gerbils, where it was taken up by efferent axon terminals. The
      virus was then retrogradely transported to efferent cell bodies, replicated, and
      transported into synaptic endings projecting onto the efferent cells. Thirty
      animals were sacrificed at approximately 5-h increments between 75 and 105 h post
      infection after determining that shorter time points had no central infection.
      Infected cells were visualized immunohistochemically. Temporal progression of
      neuronal infection was used to determine the nature of primary and higher order
      projections to the vestibular efferent neurons. Animals sacrificed at 80-94 h
      post-inoculation exhibited immunostaining in the dorsal and ventral group of
      vestibular efferent neurons, predominately on the contralateral side. Neurons
      within the medial, gigantocellular, and lateral reticular formations were among
      the first cells infected thereafter. At 95 h, additional virus-labeled cell
      groups included the solitary, area postrema, pontine reticular, prepositus,
      dorsal raphe, tegmental, the subcoeruleus nuclei, the nucleus of Darkschewitsch,
      and the inferior olivary beta and ventrolateral subnuclei. Analysis beyond 95 h
      revealed virus-infected neurons located in the vestibulo-cerebellar and motor
      cortices. Paraventricular, lateral, and posterior hypothalamic cells, as well as
      central amygdala cells, were also labeled. Spinal cord tissue exhibited no
      labeling in the intermediolateral cell column, but scattered cells were found in
      the central cervical nucleus. The results suggest functional associations among
      efferent feedback regulation of labyrinthine sensory input and both behavioral
      and autonomic systems, and support a closed-looped vestibular feedback model with
      additional open-loop polysynaptic inputs.

PMID- 16421731
TI  - Evidence for positive force feedback during involuntary aftercontractions.
AB  - We examined the involuntary isotonic muscle aftercontraction which follows a 1
      min voluntary contraction at 60% of maximum voluntary force. Aftercontractions
      provide a unique paradigm for investigating the automatic postural control of the
      upper limb in man. Previous work has shown that the strength of these
      contractions in m. deltoid is linearly dependent on the inclination of the
      subject's body in the gravitational field. The current experiments were designed
      to test if this was due to the gravitational loading on the arm as this also
      changes with body inclination. The subject sat with the head stationary to
      prevent changes in vestibular orientation. Aftercontractions in m. deltoid were
      evoked with the normal weight of the arm present and also with arm loadings equal
      to 0, 25, 50 and 75% of this value. These reductions were produced by a counter
      lever apparatus. The results showed that the EMG amplitude of this involuntary
      contraction depended linearly on the loading of the arm. This is interpreted as
      being the result of positive load feedback. Aftercontraction EMG amplitude at
      100% load was 2.7 times greater than at 0% load. The results are discussed in the
      context of recent work on positive load feedback in man and animals.

PMID- 16421730
TI  - The Ia afferent feedback of a given movement evokes the illusion of the same
      movement when returned to the subject via muscle tendon vibration.
AB  - The aim of the present study was to further investigate the contribution of
      primary muscle spindle feedback to proprioception and higher brain functions,
      such as movement trajectory recognition. For this purpose, complex illusory
      movements were evoked in subjects by applying patterns of muscle tendon vibration
      mimicking the natural Ia afferent pattern. Ia afferent messages were previously
      recorded using microneurographic method from the six main muscle groups acting on
      the ankle joint during imposed "writing like" movements. The mean Ia afferent
      pattern was calculated for each muscle group and used as a template to pilot each
      vibrator. Eleven different vibratory patterns were applied to ten volunteers.
      Subjects were asked both to copy the perceived illusory movements by hand on a
      digitizing tablet and to recognize and name the corresponding graphic symbol. The
      results show that the Ia afferent feedback of a given movement evokes the
      illusion of the same movement when it is applied to the subject via the
      appropriate pattern of muscle tendon vibration. The geometry and the kinematic
      parameters of the imposed and illusory movements are very similar and the so
      called "two-thirds power law" is present in the reproduction of the vibration
      induced illusory movements. Vibrations within the "natural" frequency range of Ia
      fibres firing (around 30 Hz) produce clear illusions of movements in all the
      tested subjects. In addition, increasing the mean frequency of the vibration
      patterns resulted in a linear increase in the size of the illusory movements.
      Lastly, the subjects were able to recognize and name the symbols evoked by the
      vibration-induced primary muscle spindle afferent patterns in 83% of the trials.
      These findings suggest that the "proprioceptive signature" of a given movement is
      associated with the corresponding "perceptual signature". The neural mechanisms
      possibly underlying the sensory to perceptual transformation are discussed in the
      general framework of "the neuronal population vector model".

PMID- 16421732
TI  - Chlamydial infections in urology.
AB  - Chlamydia trachomatis is the most frequent cause for sexually transmitted
      diseases in European countries. The organism has an intracellular habitat with a
      very specific life cycle. A variety of diagnostic tests have been developed with
      different sensitivity and specificity. Interpretation of these tests can
      sometimes be difficult. Diseases caused by C. trachomatis in men comprise
      urethritis, prostatitis, epididymitis, infertility and reactive arthritis.
      Especially in prostatitis, the exact role of C. trachomatis is still under debate
      for the technical difficulties localizing the pathogen to the prostate. For
      treatment, only some antibiotics are effective because of the intracellular
      habitat of the pathogen. Prevention of infection comprises treatment and
      screening efforts.

PMID- 16421733
TI  - Validation of the German prostate-specific module.
AB  - Theoretically, all patients newly diagnosed with prostate cancer are faced with a
      choice of treatment options: radical prostatectomy or radio therapy. Although
      these different treatments may have no differences in terms of survival, they may
      have very different consequences on the subsequent quality of life (QoL).
      Prerequisite to analyze QoL is a reliable and valid instrument to assess these
      differences not only in terms of general QoL (EORTC QLQ-C30) but prostate
      specific symptoms with a prostate specific module as well. Therefore, the aim of
      this study was a psychometric evaluation (validation) of the prostate-specific
      module (PSM). Five historical cohort studies were put together for an empirical
      meta-analysis. The main objective was to analyze the module's psychometric
      properties. The total sample consisted of 1,185 patients, of whom 950 completed
      the QoL questionnaires (EORTC QLQ-C30 and a prostate specific module developed by
      Kuechler et al.). First step of analysis was a principal component analysis that
      revealed the following scales: urinary problems, incontinence, erectile
      dysfunction, sexual problems, problems with partner, pain, heat, nutrition, and
      psychic strain. The module showed good reliability and concurrent validity and
      very good construct validity, since the module is able to discriminate between
      different treatment regimes, tumor stages and age. The German PSM is a reliable,
      valid and applicable tool for QoL in patients with prostate cancer.

PMID- 16421734
TI  - Nuclear transport is becoming crystal clear.

PMID- 16421736
TI  - [Endoscopic diagnosis and therapy for gastrointestinal bleeding].
AB  - Gastrointestinal bleeding is still one of the most frequent medical emergencies.
      Despite improvements in endoscopic diagnosis and therapy, mortality from bleeding
      is still high (15%). Since conclusive trials are lacking, the endoscopist often
      has to rely on personal experience in the selection of therapeutic options.
      Therefore this article gives an overview of new publications in this field and
      recommendations based on personal experience.

PMID- 16421737
TI  - [The role of intraoperative ultrasound in surgery for benign nodular goiter].
AB  - BACKGROUND: In treating benign nodular goiter, selective surgery taking into
      account morphology and function is better than standard subtotal resection for
      reducing the frequency of nodules in the thyroid remnant. Intraoperative
      ultrasound (IOPUS) may additionally influence operative radicality and also the
      incidence of remaining nodules. METHODS: One hundred consecutive patients with
      benign nodular goiter were operated on with IOPUS; the specimens were compared
      with results of preoperative ultrasound and intraoperative palpation. Of these
      patients, 80 were reinvestigated after 3+/-1.6 years. A series of 80 patients
      with the same operative strategy but without IOPUS was used as control group,
      having been reinvestigated sonographically 1 year postoperatively, and was
      compared to the IOPUS group with respect to operative procedures, size of
      remnants, and sonography of lesions in thyroid remnants. RESULTS: In 35% of the
      thyroid lobes, preoperatively undetected nodules could be identified additionally
      by IOPUS, which also provided information on extent and structure in a further
      20%. It resulted in the indication for more radical surgery in 24% and greater
      tissue preservation in 10%. Compared to surgery without IOPUS, IOPUS-guided
      surgery was more radical (total lobectomy in 40% vs 24%, nonresected lobes in 16%
      vs 26%, P<0.05) and showed a lower incidence of nodules in remnants at follow-up
      (2.5% vs 12.5%, P<0.05). CONCLUSIONS: With IOPUS, more nodules are detectable,
      size and structure of the remnants are optimized, and the number of nodular
      lesions in thyroid remnants is lower. Thus, an even lower risk of recurrence can
      be expected for long-term follow-up. All in all, the routine use of IOPUS can be
      advocated, with maintenance of the selective operative strategy.

PMID- 16421735
TI  - Chromosome synapsis in Arabidopsis: analysis of the transverse filament protein
      ZYP1 reveals novel functions for the synaptonemal complex.
AB  - With respect to history, plants have provided an ideal system for cytogenetical
      analysis of the synaptonemal complex (SC). However, until recently, the
      identification of the genes that encode the SC in plants has proved elusive. In
      recent years, Arabidopsis thaliana was developed as a model system for plant
      meiosis research. As a result, there was substantial progress in the isolation of
      meiotic genes and this has recently led to the isolation of the first plant SC
      gene, ZYP1. The ZYP1 gene encodes a transverse filament (TF) protein that is
      predicted to have structural similarity to TF proteins found in other organisms.
      Analysis of plants deficient in ZYP1 expression has provided important insights
      into the function of the SC in plants. Loss of ZYP1 has only a limited effect on
      the overall level of recombination. However, it is associated with extensive
      nonhomologous recombination leading to multivalent formation at metaphase I. This
      phenomenon was not previously reported in other organisms. It is important to
      note that cytological analysis of the ZYP1 deficient lines indicates that SC
      formation is not required for the imposition of crossover interference.

PMID- 16421738
TI  - Abundant hypermethylation of SOCS-1 in clinically silent pituitary adenomas.
AB  - Janus kinase (JAK)/signal transducers and activators of transcription (STAT)
      cascade are required for cytokines, growth factors, G-proteins and hormones
      (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of
      cytokine signalling (SOCS) family of proteins. Their expression level is
      epigenetically regulated by DNA methylation. We have investigated the CpG island
      methylation status of SOCS-1 in a cohort of pituitary adenomas (PA; n=57),
      craniopharyngiomas (CP; n=30) and normal pituitary tissue (NP; n=11) using
      methylation sensitive single-strand conformation polymorphism analysis (MS-SSCP)
      and direct sequencing. SOCS-1 hypermethylation was identified in 51% (29/57) of
      surgical specimens obtained from PA patients. 83% of these tumours were
      clinically silent. In contrast, no methylation of SOCS-1 was observed in CPs or
      NPs. Quantitative real-time PCR and western blot analysis confirmed reduced SOCS
      1 expression in the majority of pituitary adenomas. The data is compatible with
      epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK
      STAT pathway in PA. This appears to contribute particularly to those tumours
      characterized by a hormone-inactive status.

PMID- 16421739
TI  - P25alpha immunoreactive but alpha-synuclein immunonegative neuronal inclusions in
      multiple system atrophy.

PMID- 16421740
TI  - Depletion of cholinergic neurons in the nucleus of the medial septum and the
      vertical limb of the diagonal band in dementia with Lewy bodies.
AB  - The cholinergic basal forebrain is divided into four subregions (Ch1-4), and
      cholinergic neuronal loss in the nucleus basalis of Meynert (Ch4) has been
      correlated with cognitive impairments in both Alzheimer's disease (AD) and
      dementia with Lewy bodies (DLB). However, the Ch1-2 regions, which provide the
      major cholinergic innervation to the hippocampus, have not been investigated in
      DLB. The purpose of this study was to reveal the cholinergic neuronal changes in
      the medial septum (Ch1) and the nucleus of the vertical limb of the diagonal band
      (Ch2) of DLB brains. Using choline acetyltransferase (ChAT) immunohistochemistry,
      we showed that the number of ChAT-immunoreactive neurons in DLB brains was
      significantly lower than the numbers in AD and non-demented (control) brains. No
      significant difference in the number of ChAT-immunoreactive neurons was found
      between the AD and control brains. Moreover, the size of the ChAT-immunoreactive
      neurons was significantly smaller in the AD and DLB brains than in the control
      brains. These results show that cholinergic neurons of the Ch1-2 regions are more
      severely affected in DLB than in AD. Our DLB cases did not fulfill the
      neuropathologic criteria for definite AD. Furthermore, some Lewy bodies were
      observed in the Ch1-2 regions. Thus, cholinergic neuronal loss in the Ch1-2
      regions might be specific to the pathology of DLB. Taking the distribution of
      cholinergic fibers in the hippocampus into consideration, this study suggests a
      possibility that hippocampal cholinergic projection is involved in Lewy-related
      neurites in the CA2-3 regions, the origin of which remains unclear.

PMID- 16421741
TI  - Commentary on hepatoblastoma minisymposium.

PMID- 16421742
TI  - Effect of photodynamic therapy on the function of the outer blood-retinal barrier
      in an in vitro model.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a well established clinical treatment
      for age-related macular degeneration (AMD), and comprises intravenous injection
      of verteporfin and subsequent application of a non-thermal laser beam to the area
      of AMD to induce selective vascular occlusion. Since there is evidence that PDT
      may cause outer blood-retinal barrier (BRB) breakdown and possibly RPE cell
      alteration, we investigated the effect of PDT on the BRB function of the RPE in
      an in vitro model. METHODS: Twenty-one monolayers of human RPE cells were
      cultured on semipermeable membranes until a stable barrier function was achieved
      as determined by transepithelial electrical resistance (TER) and sodium
      fluorescein permeability. To test the effect of PDT on the outer BRB function,
      non-thermal laser (692 nm), verteporfin or a combination of both were applied.
      TER assessment prior to and after PDT was utilized to identify changes in barrier
      function of the RPE in this in vitro model. Finally, monolayers of RPE cells were
      evaluated by transmission electron microscopy (TEM). RESULTS: No significant TER
      decrease was observed after application of non-thermal laser alone or after
      administration of verteporfin in therapeutic concentrations, but combination of
      these modalities resulted in significantly decreased TER within 4 h. Except for
      intercellular blisters, no damage to the RPE was evident in TEM. Verteporfin
      added at concentrations higher than therapeutic doses (2 mg/ml) resulted in an
      immediate decrease in TER and damage to the RPE cells. CONCLUSION: The
      combination of a therapeutic concentration of verteporfin and application of non
      thermal laser resulted in a morphologically and functionally detectable breakdown
      of the outer BRB function of the RPE without any damage to the RPE cells
      themselves in vitro. However, increasing the concentration of verteporfin can
      result in RPE cell damage.

PMID- 16421743
TI  - 25-gauge, sutureless vitrectomy and standard 20-gauge pars plana vitrectomy in
      idiopathic epiretinal membrane surgery: a comparative pilot study.
AB  - BACKGROUND: The aim of the study was to evaluate the safety and functional
      outcome of a small incision, sutureless vitrectomy in the treatment of idiopathic
      epiretinal membranes (ERM) compared with a standard 20-gauge vitrectomy system.
      METHODS: Forty-six consecutive patients with idiopathic ERM were recruited for
      this study and prospectively evaluated. In group 1 (n=26) we used a
      transconjunctival sutureless 25-gauge vitrectomy system (TSV), patients in group
      2 (n=20) were operated on using a standard 20-gauge vitrectomy system. The ERM
      was removed and the internal limiting membrane (ILM) was peeled in all eyes.
      Surgery-related complications, operating time, intraoperative balanced salt
      solution (BSS) consumption, postoperative discomfort, postoperative intraocular
      inflammation, lens opacification, and long-term visual outcome are reported and
      compared. RESULTS: No surgery-related complications were observed in either
      group. Operating time was shorter in group 1 compared with group 2 (mean 15.6 and
      29.6 min respectively). Intraoperative amount of BSS consumption was less in
      group 1 (mean 28 ml in group 1 and 42 ml in group 2). Postoperative discomfort
      and intraocular inflammation were significantly reduced in the 25-gauge group. In
      the 20-gauge group cataract formation requiring surgery was observed in two eyes.
      Visual acuity improved significantly in both groups. The 25-gauge group improved
      on average by more lines of vision and the improvement in vision was more rapid.
      CONCLUSION: The TSV system is a safe and efficient surgical technique for ERM
      surgery. Operating time is significantly reduced, minimizing surgery-induced
      trauma, and reducing postoperative intraocular inflammation and the patients'
      discomfort. The incidence of cataract formation may be less using TSV.
      Postoperative recovery is accelerated.

PMID- 16421744
TI  - Maintenance of graft compression in the adult cervical spine.
AB  - It is generally advised that the graft inserted in adult cervical spine should be
      pre-loaded with a compressive force or that the screws are inserted in a
      divergent orientation, in order to maximise compression and the chance of graft
      incorporation (Truumees et al. in Spine 28:1097-1102, 2003). However, there is
      little evidence that a compressive force is maintained once the force applicator
      has been removed, or that the divergent screws enhance compression. This study
      compared the maintenance of applied pre-load force, across cervical spine graft,
      between standard anterior plating technique with pre-load and divergent screws
      and a novel plate technique, which allows its application prior to removal of the
      force applicator. Six intact adult cadaveric human cervical spines were exposed
      by standard surgical technique. A Casper type distracter was inserted across the
      disc space of interest, the disc was removed. In 14 experiments, following the
      disc removal, an autologous iliac crest bone graft was inserted under
      distraction, together with a strain gauge pressure transducer. A resting output
      from the transducer was recorded. The voltage output has a linear relationship
      with compressive force. A standardised compressive force was applied across the
      graft through the "Casper type" distracter/compressor (7.5 kg, torque). The pre
      load compressive force was measured using a torque drill. Then two different
      procedures were used in order to compare the final applied strain on the bone
      graft. In eight experiments (procedure 1), the "Casper type"
      distracter/compressor was removed and a standard anterior cervical plate with
      four divergent screws was inserted. In six experiments (procedure 2), a novel
      plate design was inserted prior to removal of the distracter/compressor, which is
      not possible with the standard plate design. A final compressive force across the
      graft was measured. For the standard plate construct (procedure 1), the applied
      compression force is significantly greater than resting (SO/SC)--P=0.01, but the
      compression force is not maintained once the compressor is removed (SO/SR)-
      P=0.27. Final bone graft compression after plate insertion is not significantly
      different to the resting state (SO/SF)--P=0.16 (Wilcoxon's sign test for paired
      observation). Application of the plate tended to offload the graft; the final
      compressive force is 170+/-100% less than the resting force. None of the applied
      force was maintained (mean 9.5+/-8.8%). For the new plate (procedure 2), the end
      compressive force (SF) measured across the graft was greater than the resting
      force (SO) (P<0.001). Further, the novel plate application increased the
      compressive force on the graft by 712+/-484%. The final bone graft compression
      using a novel plate, which allows its application prior to removal of the force
      applicator, is significant (SO/SF)--P=0.01. Here, 77+/-10% of the applied pre
      load was maintained. The difference between the plates is significant (P<0.001).
      Conclusions are as follows: (1) Applied pre-load is not maintained across a graft
      once the force applicator is removed. (2) Divergent screws with a plate do not
      compress graft and rather tend to offload it. (3) Compressive force may be
      maintained if the plate is applied prior to the force applicator removal.

PMID- 16421745
TI  - Thoracic cord compression caused by disk herniation in Scheuermann's disease: a
      case report and review of the literature.
AB  - We present the case of a 14-year-old male with Scheuermann's disease and
      significant neurological deficit due to thoracic disk herniation at the apex of
      kyphosis. He was treated with an anterior decompression, anterior and posterior
      fusion in the same setting using plate, cage and a segmental instrumentation
      system. The patient had an excellent outcome with complete neurological recovery.

PMID- 16421746
TI  - Magnetic resonance image findings in the early post-operative period after
      anterior cervical discectomy.
AB  - If early neurological deterioration occurs following anterior cervical
      discectomy, the patient should be evaluated by urgent MRI scanning. In order to
      interpret such a scan it is essential to know what the normal post-operative MRI
      appearance is following an uncomplicated procedure. In the lumbar spine it is
      well recognized that early post-operative imaging following discectomy is
      difficult to interpret with a high rate of false positive scans. The normal
      appearance of MRI in the early post-operative period was evaluated prospectively
      in 15 patients undergoing anterior cervical discectomy without fusion for either
      cervical radiculopathy or myelopathy. MRI was performed on the first post
      operative day, at 6 weeks and 6 months. The successful outcome of the procedure
      was validated by uniform improvement of Visual Analogue Scale measurement for
      neck and arm pain, the Neck Disability Index and European Myelopathy Score as
      appropriate. In contrast to the established findings following lumbar discectomy,
      only two cases showed a persistent epidural mass in the first post-operative scan
      and this had completely resolved at 6 months. All patients had foraminal
      narrowing and root or cord compression pre-operatively. Sixty six percent of
      cases showed persistent foraminal narrowing on sequential imaging up to 6 months
      despite showing good symptomatic improvement. All cases demonstrated high signal
      in the operated disc space on T2 weighted imaging on the first post-operative day
      and this finding persisted in 13 of 15 scans performed at 6 weeks. Post contrast
      imaging demonstrated no enhancement of operated disc space and adjacent vertebral
      body on the first post-operative day, whereas all scans at 6 weeks showed
      enhancement and such enhancement persisted at 6 months in 50%. Persistent
      epidural filling defects are uncommon following successful anterior cervical
      discectomy but persistence of foraminal narrowing is common despite successful
      outcome. Enhancement of the disc space is also common and does not in itself
      imply infection.

PMID- 16421747
TI  - Early neuromuscular customized training after surgery for lumbar disc herniation:
      a prospective controlled study.
AB  - A prospective and controlled study of training after surgery for lumbar disc
      herniation (LDH). The objective was to determine the effect of early
      neuromuscular customized training after LDH surgery. No consensus exists on the
      type and timing of physical rehabilitation after LDH surgery. Patients aged 15-50
      years, disc prolapse at L4-L5 or L5-S1. Before surgery, at 6 weeks, 4, and 12
      months postoperatively, the following evaluations were performed: low back pain
      and leg pain estimated on a visual analog scale, disability according to the
      Roland-Morris questionnaire (RMQ) and disability rating index (DRI). Clinical
      examination, including the SLR test, was performed using a single blind method.
      Consumption of analgesics was registered. Twenty-five patients started
      neuromuscular customized training 2 weeks after surgery (early training group =
      ETG). Thirty-one patients formed a control group (CG) and started traditional
      training after 6 weeks. There was no significant difference in pain and
      disability between the two training groups before surgery. Median preoperative
      leg pain was 63 mm in ETG and 70 mm in the CG. Preoperative median disability
      according to RMQ was 14 in the ETG and 14.5 in the CG. Disability according to
      DRI (33/56 patients) was 5.3 in the ETG vs. 4.6 in the CG. At 6 weeks, 4 months,
      and 12 months, pain was significantly reduced in both groups, to the same extent.
      Disability scores were lower in the ETG at all follow-ups, and after 12 months,
      the difference was significant (RMQ P=.034, DRI P=.015). The results of the
      present study show early neuromuscular customized training to have a superior
      effect on disability, with a significant difference compared to traditional
      training at a follow-up 12 months after surgery. No adverse effects of the early
      training were seen. A prospective, randomized study with a larger patient sample
      is warranted to ultimately demonstrate that early training as described is
      beneficial for patients undergoing LDH surgery.

PMID- 16421748
TI  - Differences in aerodynamic characteristics of new and dysfunctional Provox 2
      voice prostheses in vivo.
AB  - Tracheoesophageal voice prostheses need to be replaced due to increased airflow
      resistance or retrograde leakage of fluid into the trachea as a consequence of
      biofilm formation. Previous in vitro studies show a change of aerodynamic
      features of biofilm covered voice prostheses after removal of the prostheses out
      of the patient. To assess these changes in an in situ situation, aerodynamic
      characteristics were measured within 45 patients at the beginning and at the end
      of the wearing process of the Provox 2 voice prosthesis. As a consequence, the
      influence of biofilm formation on aerodynamic characteristics can be evaluated.
      In the majority of cases, leakage through the prosthesis was the reason for
      replacement. No differences were found in the total flow, volume range and
      intratracheal pressure (ITP) of the voice prostheses measured. The airflow
      resistance of biofilm covered prostheses was significantly reduced compared to
      new clean prostheses. However, no correlation was found between the extent of
      biofilm and the different aerodynamic features measured. Biofilm formation on the
      Provox 2 is responsible for both reduction in airflow resistance and leakage
      through the prosthesis by deterioration of the silicone rubber material.

PMID- 16421749
TI  - Chemosensory pathways in the capitate tentacles of the hydroid Cladonema.
AB  - The introduction of an extract of Artemia into the sea water bathing tentacles
      from the hydroid Cladonema triggers a burst of electrical activity that can be
      recorded intracellularly from cnidocytes in the capitate tentacles. These bursts,
      which are composed of a variety of events, including action potentials and EPSPs,
      are Ca2+ dependent, and are abolished by pretreatment with NiCl2, suggesting that
      voltage-gated Ca2+ channels are involved in their generation or transmission.
      Intracellular injection of Lucifer Yellow and recordings from pairs of cnidocytes
      reveal that the cnidocytes are electrically coupled to one another, but that they
      are not uncoupled by heptanol. The role of these chemosensory pathways in priming
      the cnidocytes for discharge is discussed.

PMID- 16421750
TI  - Subperiosteal hemangioendothelioma of the femur.
AB  - Primary neoplastic vascular lesions of bone are rare, and include haemangiomas,
      haemangioendothelioma, epithelioid haemangioendothelioma and angiosarcoma. These
      lesions may be multicentric, and when they involve bone are typically
      intraosseous and lytic. Radiological findings are not always specific. We report
      a case of haemangioendothelioma localised to the subperiosteum of the femur, a
      site not previously described for this lesion. The nomenclature for vascular
      neoplasms in bone is discussed.

PMID- 16421751
TI  - Concurrent periosteal chondroma and enchondroma of the fibula mimicking
      chondrosarcoma.
AB  - We present a rare concurrence of enchondroma and periosteal chondroma in the
      right distal fibula that mimicked chondrosarcoma in a 13-year-old boy.
      Radiographs and CT scans showed a periosteal lesion producing saucerization
      without periosteal reaction and calcification in the distal metaphysis of the
      right fibula. MRI showed an intramedullary lesion adjacent to the periosteal
      lesion, although it was invisible at CT. There was no cortical breach on imaging
      and gross examination. Because both lesions represented benign cartilaginous
      tumors on histology, concurrent periosteal chondroma and enchondroma of the
      fibula was diagnosed. This combination in the same bone in a patient without
      enchondromatosis is exceedingly rare. Such imaging features may be confused with
      those of chondrosarcoma.

PMID- 16421753
TI  - A new ambulatory system for comparative evaluation of the three-dimensional knee
      kinematics, applied to anterior cruciate ligament injuries.
AB  - The aim of this study was to develop an ambulatory system for the three
      dimensional (3D) knee kinematics evaluation, which can be used outside a
      laboratory during long-term monitoring. In order to show the efficacy of this
      ambulatory system, knee function was analysed using this system, after an
      anterior cruciate ligament (ACL) lesion, and after reconstructive surgery. The
      proposed system was composed of two 3D gyroscopes, fixed on the shank and on the
      thigh, and a portable data logger for signal recording. The measured parameters
      were the 3D mean range of motion (ROM) and the healthy knee was used as control.
      The precision of this system was first assessed using an ultrasound reference
      system. The repeatability was also estimated. A clinical study was then performed
      on five unilateral ACL-deficient men (range: 19-36 years) prior to, and a year
      after the surgery. The patients were evaluated with the IKDC score and the
      kinematics measurements were carried out on a 30 m walking trial. The precision
      in comparison with the reference system was 4.4 degrees , 2.7 degrees and 4.2
      degrees for flexion-extension, internal-external rotation, and abduction
      adduction, respectively. The repeatability of the results for the three
      directions was 0.8 degrees , 0.7 degrees and 1.8 degrees . The averaged ROM of
      the five patients' healthy knee were 70.1 degrees (standard deviation (SD) 5.8
      degrees), 24.0 degrees (SD 3.0 degrees) and 12.0 degrees (SD 6.3 degrees for
      flexion-extension, internal-external rotation and abduction-adduction before
      surgery, and 76.5 degrees (SD 4.1 degrees), 21.7 degrees (SD 4.9 degrees) and
      10.2 degrees (SD 4.6 degrees) 1 year following the reconstruction. The results
      for the pathologic knee were 64.5 degrees (SD 6.9 degrees), 20.6 degrees (SD 4.0
      degrees) and 19.7 degrees (8.2 degrees) during the first evaluation, and 72.3
      degrees (SD 2.4 degrees), 25.8 degrees (SD 6.4 degrees) and 12.4 degrees (SD 2.3
      degrees) during the second one. The performance of the system enabled us to
      detect knee function modifications in the sagittal and transverse plane. Prior to
      the reconstruction, the ROM of the injured knee was lower in flexion-extension
      and internal-external rotation in comparison with the controlateral knee. One
      year after the surgery, four patients were classified normal (A) and one almost
      normal (B), according to the IKDC score, and changes in the kinematics of the
      five patients remained: lower flexion-extension ROM and higher internal-external
      rotation ROM in comparison with the controlateral knee. The 3D kinematics was
      changed after an ACL lesion and remained altered one year after the surgery.

PMID- 16421754
TI  - Dihydropyrimidine dehydrogenase deficiency in an Indian population.
AB  - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) deficiency is prevalent in 3-5%
      of the Caucasian population; however, the frequency of this pharmacogenetic
      syndrome in the Indian population and other racial and ethnic groups remains to
      be elucidated. PATIENTS AND METHODS: We describe an Indian patient who presented
      to clinic for the treatment of gastric adenocarcinoma with 5-flurouracil (5-FU)
      therapy who subsequently was diagnosed with DPD deficiency by using the
      peripheral blood mononuclear cell (PBMC) DPD radioassay. This observation
      prompted us to examine the data generated from healthy (cancer-free) Indian
      subjects who were enrolled in a large population study to determine the
      sensitivity and specificity of the uracil breath test (UraBT) in the detection of
      DPD deficiency. Thirteen Indian subjects performed the UraBT. UraBT results were
      confirmed by PBMC DPD radioassay. RESULTS: The Indian cancer patient demonstrated
      reduced DPD activity (0.11 nmol/min/mg protein) and severe 5-FU toxicities
      commonly associated with DPD deficiency. Of the 13 Indian subjects [ten men and
      three women; mean age, 26 years (range: 21-31 years)] enrolled in the UraBT, 12
      Indian subjects demonstrated UraBT breath profiles and PBMC DPD activity within
      the normal range; one Indian subject demonstrated a reduced breath profile and
      partial DPD deficiency. CONCLUSIONS: DPD deficiency is a pharmacogenetic syndrome
      which is also present in the Indian population. If undiagnosed, the DPD
      deficiency can lead to death. Future epidemiological studies would be helpful to
      determine the prevalence of DPD deficiency among racial and ethnic groups,
      allowing for the optimization of 5-FU chemotherapy.

PMID- 16421752
TI  - Variability of diurnality in laboratory rodents.
AB  - The locomotor activity rhythms of domestic mice, laboratory rats, Syrian
      hamsters, Siberian hamsters, Mongolian gerbils, degus, and Nile grass rats were
      compared. Running-wheel activity was monitored under a light-dark cycle with 12 h
      of light and 12 h of darkness per day. Nile grass rats were found to be reliably
      diurnal, whereas laboratory rats, Siberian hamsters, domestic mice, and Syrian
      hamsters were reliably nocturnal. Both diurnal and nocturnal subgroups were
      observed in Mongolian gerbils and degus. A downward gradient of diurnality was
      observed from Mongolian gerbils classified as diurnal, degus classified as
      diurnal, gerbils classified as nocturnal, and degus classified as nocturnal.
      Nocturnal degus remained nocturnal when tested with an infrared motion detector
      without running wheels. Thus, although the diurnal-nocturnal dichotomy could be
      applied to some of the species, it was not appropriate for others. The dichotomy
      may reflect researchers' needs for systematization more than a natural
      distinction between species. Through mechanisms as yet poorly understood, the
      balance between entraining and masking processes seems to generate a gradient of
      temporal niches that runs from predominantly diurnal species to predominantly
      nocturnal species with many chronotypes in between, including species that
      exhibit wide intra-species gradients of temporal niche.

PMID- 16421755
TI  - Dendritic cell infiltration and prognosis of human hepatocellular carcinoma.
AB  - AIM: To elucidate the relationship between local immunocompetent cells and
      prognosis of human hepatocellular carcinoma (HCC) after resection. METHODS: HE
      staining and immunohistochemical study were carried out on specimens from
      patients underwent surgical resection. Local immunocompetent cells, such as
      dendritic cells (DCs), memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes,
      were counted and their relationships with tumor-free survival rate were analyzed
      by grouping DCs with the T lymphocytes retrospectively. RESULTS: The number grade
      of infiltrating immunocompetent cells in HCC nodules and pericancerous tissues
      under HE staining had no significant correlation with tumor-free survival time
      (P=0.054, 0.071, respectively). DCs were mainly among tumor cells, encircling
      tumor cells with their pseudopodia and were in contact with T lymphocytes. A
      certain number of DCs in HCC nodules (> or =25/10HPF) statistically correlated to
      tumor-free survival time (P=0.005), while a certain number of DCs in
      pericancerous tissues (> or =28/10HPF) had no correlation with tumor-free
      survival time (P=0.329). The number of memory T cells, CD3+ T lymphocytes and
      CD8+ T lymphocytes in HCC nodules strongly correlated to tumor-free survival time
      (P=0.003, 0.005, 0.037, respectively). The tumor-free survival rate curves
      revealed that the more DCs or together with memory T cells/CD3+ T lymphocytes or
      that the more CD8+ T lymphocytes were detected in HCC nodules, the better the
      prognosis would be. CONCLUSIONS: Marked infiltration of DCs in HCC nodules was
      closely related to the prognosis of HCC after surgical resection and can be
      served as a predictive index for recurrence and metastasis of HCC.

PMID- 16421756
TI  - Behavioural and life history effects of predator diet cues during ontogeny in
      damselfly larvae.
AB  - A central issue in predator-prey interactions is how predator associated chemical
      cues affect the behaviour and life history of prey. In this study, we
      investigated how growth and behaviour during ontogeny of a damselfly larva
      (Coenagrion hastulatum) in high and low food environments was affected by the
      diet of a predator (Aeshna juncea). We reared larvae in three different predator
      treatments; no predator, predator feeding on conspecifics and predator feeding on
      heterospecifics. We found that, independent of food availability, larvae
      displayed the strongest anti-predator behaviours where predators consumed prey
      conspecifics. Interestingly, the effect of predator diet on prey activity was
      only present early in ontogeny, whereas late in ontogeny no difference in prey
      activity between treatments could be found. In contrast, the significant effect
      of predator diet on prey spatial distribution was unaffected by time. Larval size
      was affected by both food availability and predator diet. Larvae reared in the
      high food treatment grew larger than larvae in the low food treatment. Mean
      larval size was smallest in the treatment where predators consumed prey
      conspecifics, intermediate where predators consumed heterospecifics and largest
      in the treatment without predators. The difference in mean larval size between
      treatments is probably an effect of reduced larval feeding, due to behavioural
      responses to chemical cues associated with predator diet. Our study suggests that
      anti-predator responses can be specific for certain stages in ontogeny. This
      finding shows the importance of considering where in its ontogeny a study
      organism is before results are interpreted and generalisations are made.
      Furthermore, this finding accentuates the importance of long-term studies and may
      have implications for how results generated by short-term studies can be used.

PMID- 16421757
TI  - The influence of temperature and host availability on the host exploitation
      strategies of sexual and asexual parasitic wasps of the same species.
AB  - In the hymenopteran parasitoid Venturia canescens, asexual (obligate thelytoky
      not induced by Wolbachia bacteria) and sexual (arrhenotokous) wasps coexist in
      field conditions despite the demographic cost incurred due to the production of
      males by sexual females. Arrhenotoky predominates in field conditions, whereas
      populations in indoor conditions (mills, granaries) are exclusively thelytokous.
      These differences in the relative abundance of the two modes of reproduction
      between environments suggest that the individuals of each reproductive mode may
      have developed strategies adapted to the conditions prevailing in each kind of
      habitat. The two environments contrast in temperature variability and in the
      spatial heterogeneity of host availability. In this study, we considered the
      combined effect of temperature and host availability on host patch exploitation
      by thelytokous and arrhenotokous V. canescens. As expected, arrhenotokous females
      were more sensitive to temperature changes. If the temperature decreased before
      foraging, they remained longer and exploited patches more thoroughly. This is
      consistent with the expected behaviour of parasitoids in response to signs of
      unfavourable conditions that entail increasing risk of time limitation or a
      reduced probability of attaining further patches. Both arrhenotokous and
      thelytokous females increased patch exploitation with host availability. However,
      unexpectedly, we found no difference in the way the two types of wasp responded
      to differences in host availability. Differences in the strategies adopted under
      different environmental conditions may indicate divergence of niche-specific life
      history traits between the two modes of reproduction. Niche displacement may
      partly account for the coexistence of these two modes of reproduction at a
      geographical scale.

PMID- 16421758
TI  - Executive brain functions after exposure to nocturnal traffic noise: effects of
      task difficulty and sleep quality.
AB  - The after-effects of nocturnal traffic noise on cognitive performance and
      inhibitory brain activity were investigated. Twenty participants (18-30 years)
      performed an easy and a difficult visual Go/Nogo task with simultaneous EEG
      recording after a quiet night and then during three nights when aircraft noise
      was presented with equivalent noise levels of 39, 44, and 50 dBA, respectively,
      between 11 p.m. to 7 a.m. Based on subjective sleep quality rating, participants
      were separated into "good" versus "bad" sleepers. The performance and inhibition
      related components (N2, P3) of event-related potentials were analysed. The N2 and
      P3 amplitudes were smaller and latencies were prolonged in the difficult than in
      the easy task. This effect was more pronounced for Nogo than for Go trials. The
      Nogo-P3 amplitude was smaller in Noise than in "Quiet" conditions in the
      difficult task only. In the difficult task, the Nogo-P3 latency was prolonged in
      bad sleepers than in good sleepers. The Nogo-P3 amplitude was reduced in Noise as
      compared to "Quiet" conditions in bad sleepers only. Sleep quality in bad
      sleepers worsened steadily with increasing noise levels. No effects of noise or
      subjective sleep quality on performance were found. Inhibitory processes appear
      to be selectively impaired after nocturnal noise exposure. The task difficulty
      and perceived sleep quality are important factors modulating noise effects. The
      results suggest that nocturnal traffic noise increase physiological costs for
      inhibitory functioning on the day even if no overt performance decrement is
      observed.

PMID- 16421759
TI  - [Lymphogranuloma venereum. Two cases from Dresden].
AB  - Lymphogranuloma venereum (LGV) caused by Chlamydia trachomatis serovar L1-3 was
      formerly a rare sexually transmitted disease in western countries. Recently, an
      outbreak of LGV and LGV proctitis among men who have sex with men (MSM) was
      reported from the Netherlands. We report two cases from Dresden, Germany, of
      white HIV1-infected MSM who presented in November 2004 with genital ulcers along
      with inguinal lymphadenitis (case 1) and ulcerative proctitis (case 2). The
      clinical picture and high titers of serum IgG and IgA antibodies pointed to
      infection with Chlamydia trachomatis. Appropriate specimens were positive for
      Chlamydia trachomatis with culture and PCR. Subsequent genotyping of the major
      outer membrane protein (MOMP) by restricted fragment length polymorphism
      confirmed serovar L2. Treatment with doxycycline for 3-4 weeks was effective. The
      incidence of LGV is increasing among MSM in Europe. Since most of the reported
      cases have been HIV1-infected and ulcerative STDs enhance HIV transmission, both
      health care providers and patients should be more aware of LGV.

PMID- 16421760
TI  - [Hematogenous contact eczema induced by foods].
AB  - Oral ingestion or parenteral administration of certain contact allergens may
      elicit eczematous skin reactions "from inside" in sensitized individuals; this
      phenomenon has been termed "systemically-induced eczema" or "hematogenous contact
      eczema". There is a wide range of clinical features from polyetiological
      dyshidrotic hand and foot eczema to baboon syndrome. The most important contact
      allergens known to elicit systemically-induced contact eczema are metal salts,
      drugs, phytoallergens and balsam of Peru. Diagnosis is based on proof of delayed
      type hypersensitivity by patch testing and oral challenge. Until more and better
      data is acquired, special diets (for instance low nickel) should be instituted
      only in carefully selected patients.

PMID- 16421761
TI  - [Cutaneous symptoms after ingestion of pollen-associated foodstuffs].
AB  - The molecular basis of pollen-related food allergy is the marked similarity in
      sequence and structure of allergenic proteins in pollens and food plants. In
      affected patients, specific IgE antibodies are primarily directed against pollen
      allergens but then recognize homologous allergens in plant food. In Central and
      Northern Europe up to 80% of birch pollen allergic subjects suffer from a food
      allergy, in particular to stone- and pip fruits, nuts and vegetables. The main
      clinical manifestation of pollen-related food allergy is the oral allergy
      syndrome (OAS), a contact urticaria of the oral mucosa. Other features include
      contact urticaria of the hands in those handling the foods, as well as
      generalized urticaria and angioedema following ingestion. The impact of pollen
      related food allergy on the severity and course of atopic eczema remain to be
      elucidated.

PMID- 16421762
TI  - [What's your diagnosis? Lichenification of flexures, tetraspasm and mental
      retardation].

PMID- 16421763
TI  - Measuring nuclear factor-KB--who cares?

PMID- 16421764
TI  - Expert meeting: hypopituitarism after traumatic brain injury and subarachnoid
      haemorrhage.

PMID- 16421765
TI  - Prognostic value of perfusion-weighted imaging in brain glioma: a prospective
      study.
AB  - OBJECT: Biopsy targeting based on MR imaging alone may fail to identify malignant
      areas in brain gliomas. Considering the differences in relative Cerebral Blood
      Volume (rCBV) ratios reported among tumour grades, we evaluated whether perfusion
      weighted MR imaging (PWI) could usefully implement the routine preoperative
      imaging by detecting those areas bearing a higher yield for malignancy to guide
      the stereotactic biopsy or the surgical removal. CLINICAL MATERIAL AND METHODS:
      We studied a series of 55 consecutive patients with newly diagnosed brain glioma
      using both conventional MR imaging and PWI in the preoperative assessment. The
      pathological diagnosis was established by stereotactic biopsy in 29 cases and by
      craniotomy in 24 cases. We evaluated the patient survival to detect undergrading.
      DISCUSSION: Independent from contrast-enhancement, perfusion-weighted MR imaging
      improved the target selection in stereotactic biopsy guidance and the removal of
      malignant areas in tumours amenable to surgery. Particularly sensitive to the
      perfused part of the tumour as to small regional changes, rCBV maps allowed a
      better detection of malignant areas. The rCBV ratios correlated significantly to
      the tumour grade and the final outcome (p < 0.01). CONCLUSIONS: We found PWI
      valuable in the preoperative assessment of brain gliomas, discriminating high
      from low-grade gliomas. PWI can easily be performed on widely available MR
      imaging systems as part of the routine imaging of gliomas.

PMID- 16421766
TI  - Intracranial neurenteric cyst with recurrence and extensive craniospinal
      dissemination.
AB  - Neurenteric cyst represents a rare cystic lesion of the central nervous system,
      and is generally thought to result from failure of separation of neuro-ectodermal
      and endodermal elements during week 3 of embryogenesis. Although recurrences have
      been reported, only one case of craniospinal dissemination has previously been
      reported. We describe a unique intracranial neurenteric cyst with recurrence and
      dissemination to the spinal cord.

PMID- 16421768
TI  - Digital repeat analysis; setup and operation.
AB  - Since the emergence of digital imaging, there have been questions about the
      necessity of continuing reject analysis programs in imaging departments to
      evaluate performance and quality. As a marketing strategy, most suppliers of
      digital technology focus on the supremacy of the technology and its ability to
      reduce the number of repeats, resulting in less radiation doses given to patients
      and increased productivity in the department. On the other hand, quality
      assurance radiographers and radiologists believe that repeats are mainly related
      to positioning skills, and repeat analysis is the main tool to plan training
      needs to up-skill radiographers. A comparative study between conventional and
      digital imaging was undertaken to compare outcomes and evaluate the need for
      reject analysis. However, digital technology still being at its early development
      stages, setting a credible reject analysis program became the major task of the
      study. It took the department, with the help of the suppliers of the computed
      radiography reader and the picture archiving and communication system, over 2
      years of software enhancement to build a reliable digital repeat analysis system.
      The results were supportive of both philosophies; the number of repeats as a
      result of exposure factors was reduced dramatically; however, the percentage of
      repeats as a result of positioning skills was slightly on the increase for the
      simple reason that some rejects in the conventional system qualifying for both
      exposure and positioning errors were classified as exposure error. The ability of
      digitally adjusting dark or light images reclassified some of those images as
      positioning errors.

PMID- 16421769
TI  - Echocardiographic evaluation of coronary artery fistula in pediatric patients.
AB  - The management of pediatric patients with coronary artery fistula (CAF) remains
      controversial because the clinical course of CAF may vary greatly from
      spontaneous closure to severe complications. The purpose of our study was to
      report the outcome of CAF in pediatric patients by using echocardiography as an
      evaluation tool. Between January 1997 and July 2003, 17 patients (age range, 5
      months to 14 years; mean, 3.8 years) with coronary angiographically proven CAF
      were recruited. We divided patients into two groups. Group 1 (n = 4) included
      patients with symptoms related to CAF (n = 3), persistent coronary artery
      dilatation for 6 months (n = 4), and/or a continuous waveform of the fistula
      detected by Doppler (n = 3). Group 2 (n = 13) included patients who were
      asymptomatic, with normal coronary artery size or coronary artery dilatation less
      than 6 months, and/or a noncontinuous waveform of the fistula detected by
      Doppler. Group 1 patients received interventional therapy, whereas group 2
      patients were managed conservatively. There were 6 male and 11 female patients.
      The correlation coefficient of coronary artery diameter measured on
      echocardiography and angiography was 0.935 and 0.834 in groups 1 and 2,
      respectively. The diameter of the involved coronary artery was 5.8-9.2 mm (mean,
      7.50 +/- 1.85) and 1.7-3.8 mm (mean, 2.72 +/- 0.59) in group 1 and group 2,
      respectively. After transcatheter coil embolization, group 1 patients became
      asymptomatic with no residual fistula and had decrement of the coronary artery
      diameter (p = 0.035). All group 2 patients remained asymptomatic with no
      significant change in coronary artery size (p = 0.846) and 3 of them showed
      spontaneous closure of CAF. Persistent dilatation of the diameter of proximal
      coronary artery may be a useful parameter for determining subsequent application
      of interventional therapy. In patients with nonsignificant CAF, conservative
      follow-up is strongly suggested and intervention procedures may be unnecessary.

PMID- 16421767
TI  - Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure? A
      critical review and meta-analysis for patients who fail in vitro fertilization
      and embryo transfer (IVF).
AB  - PROBLEM: Intravenous Immunoglobulins (IVIG) are widely used off label in the
      treatment of early reproductive failure. As IVIG is expensive, and may have side
      effects, evidence of efficacy is needed. Previous results have suggested that the
      pre-conception treatment of primary recurrent abortion patients might be
      effective, but the data set has been too small for adequate statistical power.
      More recently it has been suggested that IVIG may improve the success rate of in
      vitro fertilization and embryo transfer (IVF) in patients with prior IVF
      failures, but clinical trials have given conflicting results that need
      explanation. Systematic reviews generating inconclusive results have focused on
      methodological rigor to the exclusion of biological plausibility. METHODS: Review
      of current basic science of design, measurement, and evaluation of clinical
      trials and basic science mechanisms providing a rationale for treatment. Meta
      analysis of published randomized controlled and cohort-controlled trials (updated
      with two unpublished data sets) evaluating IVIG treatment in IVF failure
      patients. Live birth rate was used as the most relevant endpoint. The ability of
      different sources of IVIG to suppress natural killer (NK) cell activity was
      determined using a standard (51)Cr-release assay in vitro. RESULTS AND
      CONCLUSIONS: Meta-analysis of three published randomized controlled trials (RCTs)
      of IVIG in IVF failure patients shows a significant increase in the live birth
      rate per woman (p = 0.012; Number Needed to Treat for 1 additional live birth,
      NNT = 6.0 women). Using live birth rate per embryo transferred, and adding data
      from two cohort-controlled trials to the meta-analysis further supports this
      conclusion (overall p = 0.000015, NNT = 3.7 women). Relevant variables appear to
      include properties and scheduling of the IVIG, and selection of patients with
      abnormal immune test results. Different IVIG preparations vary significantly in
      their ability to suppress NK activity in vitro. A rationale for use of IVIG is
      provided by a review of mechanisms of IVIG action and mechanisms underlying
      failure of chromosomally normal embryos.

PMID- 16421771
TI  - Around PediHeart: what should be done for fetal rhabdomyomata.

PMID- 16421770
TI  - The epidemiology of Kawasaki disease in an urban hospital: does African American
      race protect against coronary artery aneurysms?
AB  - The etiology and pathogenesis of Kawasaki disease (KD) is largely unknown.
      Certain demographic factors and laboratory findings are predictive of the
      development of coronary artery (CA) aneurysms. The objectives of this study were
      to determine the epidemiology of KD patients in an urban hospital and determine
      risk factors associated with their development of CA abnormalities. A
      longitudinal case series of KD patients admitted to Children's National Medical
      Center from 1990 to 2002 was examined. Age, sex, ethnic background, duration of
      fever prior to diagnosis, address, month diagnosed, and CA abnormalities (ectasia
      or aneurysms) on echocardiography were recorded. Median household income was
      obtained from the U.S. Census Bureau Web site. The Student t-test, logistic
      regression analyses, and the Kruskal-Wallis test were used, with significance
      assumed at p < 0.05. A total of 302 patients were evaluated. CA abnormalties were
      found in 27 patients (9%), with aneurysms identified in 13 patients (4%). Age was
      2.9 +/- 2.4 years (range, 2 months to 14 years). A total of 51 patients (16%)
      were < or =1 year and 35 patients (12%) were > or =5 years. Ethnic distribution
      was 54% (164) African American, 24% (72) Caucasian, 9% (29) Asian/Pacific
      Islander, 8% (23) Hispanic, and 5% (14) Middle Eastern. Only 2/164 (1.2%) African
      Americans developed CA aneurysms. Neighborhood median income of the cohort was
      $45,400 +/- $21,200 ($52,200 +/-$25,800 for patients with aneurysms). A total of
      28% of cases clustered between December and January. Cases doubled annually in
      1999-2001 compared to 1990-1998 (39 vs 19). Multivariate logistic regression
      found age between 1 and 5 years [p = 0.045; odds ratio, 0.31; 95% confidence
      interval (CI), 0.10-0.97] and African American race (p = 0.014; odds ratio, 0.15;
      95% CI, 0.03-0.68) to be independently protective against CA aneurysms. Duration
      of fever prior to diagnosis, considered in 210 patients, was different between
      patients with and without aneurysms (11 +/- 5.3 vs 6.5 +/- 3.8 days,
      respectively, p = 0.0007). Multivariate logistic regression found fever longer
      than 5 days to be the only predictive factor associated with the development of
      aneurysms and any abnormality. African Americans had a shorter duration of fever
      than the rest of the cohort (6.03 vs 7.31 days), (p = 0.0087). The epidemiology
      of KD at our hospital is similar to that at other centers except for the
      predominance of African Americans with a shorter duration of fever prior to
      diagnosis and a decreased incidence of CA aneurysms compared to other
      ethnicities. The protective nature of African American ethnicity against the
      development of CA aneurysms raises speculation about the role of genetics and its
      interaction with immunity in the pathogenesis of KD.

PMID- 16421772
TI  - Around PediHeart: hemodynamic indications for chemoprophylaxis.

PMID- 16421775
TI  - Another role for ultrasonography in the management of breast cancer.

PMID- 16421776
TI  - [Developments in psychotherapeutic health care--what would have been the comments
      of Adolf-Ernst Meyer?].

PMID- 16421777
TI  - [Standardized diagnosing: computer-assisted (CIDI) diagnoses compared to
      clinically-judged diagnoses in a psychosomatic setting].
AB  - BACKGROUND: Within the past two decades, there has been an increasing trend
      towards the use of empirically-based, standardized instruments to diagnose mental
      disorders. The purpose of this study was to investigate the congruence between
      clinically-derived and standardized computerized diagnoses using the Composite
      International Diagnostic Interview (CIDI) in a psychosomatic setting. PATIENTS
      AND METHODS: N = 230 inpatients treated at the Department of Psychosomatic
      Medicine, Charite Berlin, were diagnosed for mental disorders by experienced
      clinicians and by the CIDI according to the diagnostic criteria of ICD-10 and DSM
      IV. RESULTS: Congruence between computerized and clinically-derived diagnoses for
      all mental disorders was fair to poor (kappa = 0.0 - 0.33). The diagnostic
      congruence of somatoform (F45), anxiety (F40 - 41), depressive (F32 - 34), eating
      (F50) and dissociative disorders (F44) and disorders due to psychoactive
      substance use (F10 - 19) was fairly low (kappa = 0.19 - 0.33). Diagnostic
      congruence of diagnoses of reactions to severe stress (F43) and obsessive
      compulsive disorders (F42) was particularly poor (kappa = 0.0 - 0.01).
      CONCLUSION: Overall diagnostic congruence between computerized and clinical
      diagnostics was unsatisfactory. Thus, the validity of computer-assisted
      standardized interviews - like the CIDI - is questionable in a psychosomatic
      setting.

PMID- 16421778
TI  - [How relevant are the benefits for participation at working life for
      psychosomatic inpatient rehabilitation].
AB  - Beside the stabilization of the health status the reintegration into employment
      are the main ambitions of the medical rehabilitation. Thereby occupational
      rehabilitation plays an important role in the rehabilitation system. To recommend
      occupational rehabilitation physicians have to know the requirements patients
      have to comply with. In addition formal conditions of the medical report upon
      discharge have to be accomplish that benefits for participation at working life
      will be provided by the pension insurance. In our study the differences of the
      amount of recommendation for occupational rehabilitation and the appraisal of the
      ability to work in the medical reports upon discharge of psychosomatic and
      orthopaedic patients are examined. The results show that psychosomatic patients
      achieved significantly less recommendations for occupational rehabilitation than
      orthopaedic patients. At the same time more psychosomatic patients who achieved
      the recommendation didn't claim benefits for participation at working life. In
      addition orthopaedic patients get a rehabilitation approval certification more
      often than psychosomatic patients. At the same time it appears that maybe the
      recommending clinics were insecure about the connection between the occupational
      capacity assessment and the recommendations for benefits for participation at
      work life. The outcomes presume that work place problems in medical
      rehabilitation are not taken into consideration adequately.

PMID- 16421779
TI  - [Application of standardized patients in teaching, learning and assessment].
AB  - The new German requirements for Licensure to practice medicine focus on teaching
      clinical skills. It will become difficult for Medical Schools to fulfil these new
      requirements in the training of medical students with the increasing cost
      effectiveness in patient care. Standardized patients can be a very useful tool in
      teaching clinical skills. Implementation of a standardized patients program
      provides a quasi-real but safe learning environment in which students can acquire
      skills in physical examination, history taking, interpersonal and communication
      skills. These skills can also be assessed in this environment.

PMID- 16421780
TI  - [Anxiety and depression in chronic back pain patients: effects on beliefs of
      control and muscular capacity].
AB  - Chronic back pain patients often show a fear- and depression-related behavior
      with social retreat and less physical activity. Increasing pain is associated by
      decreasing muscular capacity of the spine stabilizing muscular system. The aim of
      the present study was to analyse the level of anxiety and depression (HADS-D)
      among chronic low back pain patients (n = 685) in ambulatory treatment in
      comparison with standardised values of a representative German adult population
      sample (n = 1943). Furthermore, the association between conspicuous values of
      anxiety or depression and beliefs of control (KU-WS) and muscular capacity
      (isometric power of lumbal extensor and flexor) were analysed. Back pain patients
      showed significantly higher mean scores in anxiety and depression without a
      significantly correlation to the age. Female subjects were more anxious than
      males. 14.9 % showed conspicuous values of anxiety, 16.1 % of depression.
      Patients with conspicuous values of anxiety and depression respectively showed
      lower levels of internal beliefs of control and muscular capacity. The present
      study confirms the importance of early anxiety and depression screening in
      patients with low back pain in ambulatory treatment to figure out risks of
      chronicity and to derive optimal treatment.

PMID- 16421781
TI  - Clinical and immunological comparison of smallpox vaccine administered to the
      outer versus the inner upper arms of vaccinia-naive adults.
AB  - BACKGROUND: Current recommendations direct health care providers to administer
      smallpox vaccine to the upper outer arm. However, concerns about cosmetically
      bothersome scarring, accidental contact transmission, interference by body
      tattoos, and even malignant transformation suggest evaluation of alternate
      vaccination sites is warranted. METHODS: We randomized 20 vaccinia-naive adults
      to undergo smallpox vaccination on the outer (n = 10) or inner (n = 10) upper
      arm. Evaluations included major reaction ("take") rates and vaccination site
      cultures on postvaccination day 7, determination of serum vaccinia-specific
      neutralizing antibody titers on days 0 (prevaccination) and 21, and determination
      of adverse events. RESULTS: On postvaccination day 7, a total of 18 participants
      (9 per group) had major reactions, 17 of whom had culture evidence of viable
      vaccinia. The inner and outer arm groups had similar major reaction mean sizes (P
      = .17), but the amount of erythema (in square centimeters) was smaller in the
      inner arm group (P = .05). At day 21, all participants had higher titers of
      vaccinia-specific neutralizing antibodies, compared with at day 0, and the
      geometric mean titer values of the 2 vaccine groups were similar (P = .45).
      Adverse event rates were similar. CONCLUSION: The comparable clinical,
      immunological, and tolerability outcomes between smallpox vaccine applied to the
      conventional upper outer arm site versus the upper inner arm, coupled with
      modestly less vaccine-site erythema on the inner arm, indicate that the inner arm
      may be a suitable alternate vaccination site.

PMID- 16421782
TI  - Ganciclovir is associated with low or undetectable Epstein-Barr virus DNA load in
      cerebrospinal fluid of patients with HIV-related primary central nervous system
      lymphoma.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is pathogenically linked to human
      immunodeficiency virus (HIV)-related primary central nervous system lymphoma
      (PCNSL) and is found in virtually all HIV-related PCNSL cases. The objective of
      this study was to assess the effect of ganciclovir on EBV DNA replication in
      patients with HIV-related PCNSL. PATIENTS AND METHODS: EBV DNA was measured by
      real-time polymerase chain reaction in cerebrospinal fluid and plasma samples
      from 25 patients with HIV-related PCNSL. Eight of these patients were receiving
      ganciclovir for concurrent cytomegalovirus infections. RESULTS: EBV DNA was
      detected in cerebrospinal fluid samples obtained from 15 (88%) of 17 ganciclovir
      untreated patients and 4 (50%) of 8 ganciclovir-treated patients (P = .028). EBV
      DNA load was significantly lower for treated patients, compared with untreated
      patients (median value, 2.15 vs. 4.16 log copies/mL; P = .001). Analysis of
      sequential cerebrospinal fluid samples from 7 patients showed that EBV DNA
      decreased in samples obtained from 2 patients following the start of ganciclovir
      administration but did not decrease in samples obtained from the 5 untreated
      patients. In addition, patients who received ganciclovir survived longer than the
      untreated patients (median duration of survival, 181 vs. 72 days; P = .006).
      CONCLUSION: The effect of ganciclovir on EBV DNA load in cerebrospinal fluid
      supports the hypothesis that EBV is replicating in patients with PCNSL. This
      observation, together with the effect of ganciclovir therapy on patient survival,
      suggests that this drug might be useful for the management of PCNSL.

PMID- 16421783
TI  - Cytomegalovirus ventriculoencephalitis in a peripheral blood stem cell transplant
      recipient.
AB  - Cytomegalovirus encephalitis occurs rarely in transplant recipients. We describe
      a patient with cytomegalovirus ventriculoencephalitis who had a very high CSF
      viral load but a low peripheral blood viral load. No resistance mutations were
      present in cerebrospinal fluid viral DNA, whereas DNA from blood showed a
      resistance mutation in the UL54 gene but not in the UL97 gene. Viral replication
      was intense in the brain ependyma and periventricular areas without evidence of
      peripheral cytomegalovirus disease. The data provide evidence for
      compartmentalization of cytomegalovirus infection. Levels of ganciclovir and
      foscarnet in the cerebrospinal fluid may be inadequate for treatment, even for
      some drug-susceptible strains, and, together with periventricular replication,
      may explain the disparity between cerebrospinal fluid viral load and peripheral
      blood viral load.

PMID- 16421784
TI  - Management of potential neurocysticercosis in patients with HIV infection.
AB  - In patients with human immunodeficiency virus, the diagnosis of
      neurocysticercosis can be complex, and the current diagnostic criteria may not
      apply. We report 3 cases and suggest including the CD4+ T lymphocyte count as an
      important factor in the proper diagnosis and treatment of patients with human
      immunodeficiency virus and potential neurocysticercosis.

PMID- 16421785
TI  - Temporal changes in streptococcal M protein types and the near-disappearance of
      acute rheumatic fever in the United States.
AB  - BACKGROUND: The explanation for the very substantial decrease in the incidence of
      acute rheumatic fever in the United States, particularly over the past 50 years,
      is unclear. It has been proposed that certain M types of group A streptococci
      (GAS) include strains that are particularly rheumatogenic and that others are
      nonrheumatogenic. METHODS: We compared the M type distribution of GAS recovered
      from children from Chicago, Illinois, with acute pharyngitis during 1961-1968 to
      that of GAS recovered from Chicago children and children from across the United
      States in 2000-2004, with attention to changes in M types that previously were
      associated with rheumatogenic strains. RESULTS: The rheumatogenic types 3, 5, 6,
      14, 18, 19, and 29 comprised 49.7% of 468 pharyngeal isolates during 1961-1968
      but only 10.6% of 450 Chicago isolates during 2000-2004 (P < .001) and 17.9% of
      3969 isolates nationwide during 2000-2004 (P < .001). Significant decreases in
      types 3, 5, and 6 and virtual disappearance of types 14, 18, 19, and 29 occurred
      between the 2 study periods. No change in the proportion of type 1 isolates, a
      highly heterogeneous group that includes some rheumatogenic strains, was
      observed. The nonrheumatogenic GAS types 2, 4, 22, and 28 increased from 4.9% to
      approximately 28% of pharyngeal isolates in Chicago and nationwide between the 2
      study periods (P < .001). CONCLUSIONS: These data support the concept of
      rheumatogenic strains of GAS and indicate that the marked decrease in the
      incidence of acute rheumatic fever in the United States over the past 4 decades
      is correlated with the replacement of rheumatogenic types by nonrheumatogenic
      types in cases of acute streptococcal pharyngitis in children. The reasons
      underlying the observed change in distribution of M types remain to be
      elucidated.

PMID- 16421786
TI  - Changing epidemiology of acute rheumatic fever in the United States.

PMID- 16421787
TI  - Clonal and capsular types decide whether pneumococci will act as a primary or
      opportunistic pathogen.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of morbidity and mortality
      worldwide. The role of the different capsular and clonal types in invasive
      disease severity remains to be defined. METHODS: Disease severity and disease
      type were correlated to age, underlying disease, capsular serotype, and clonal
      type of the causative agent for 494 adult patients with invasive pneumococcal
      disease. RESULTS: Pneumococcal isolates of serotypes 1 and 7F were genetically
      homogenous, had the highest potential to infect previously healthy individuals,
      and were not causing deaths. Also, type 1 isolates were only found among younger
      adults, whereas other serotypes were mainly found among elderly persons (e.g.,
      type 23F). Some serotypes and/or clones were more prone to cause more-severe
      disease, as observed by high APACHE II scores calculated at admission, and were
      also associated with a high mortality (e.g., clones of type 3 and 11A). We found
      no evidence of an impact of penicillin resistance on disease severity and disease
      type. CONCLUSIONS: We suggest that clones with capsular types 1 and 7F, which are
      known to have a high invasive disease potential, behave as primary pathogens,
      whereas clones with other capsular types with a lower relative risk of causing
      invasive disease are more opportunistic, primarily affecting patients with
      underlying disease. Disease caused by the latter group, however, was more severe,
      even in previously healthy individuals.

PMID- 16421788
TI  - Capsular type and the pneumococcal human host-parasite relationship.

PMID- 16421789
TI  - Conjunctival chlamydial 16S ribosomal RNA expression in trachoma: is chlamydial
      metabolic activity required for disease to develop?
AB  - BACKGROUND: Nucleic acid amplification testing frequently detects conjunctival
      Chlamydia trachomatis infection in subjects without clinical signs of trachoma.
      It is unclear whether such subjects are actually infected. We measured chlamydial
      16S ribosomal RNA (rRNA) expression, a marker of chlamydial metabolic activity,
      in comparison with the quantitation of a chlamydial DNA target in subjects
      exposed to trachoma. METHODS: Subjects from 2 Gambian villages where trachoma was
      endemic were examined. Conjunctival samples were tested for the presence of C.
      trachomatis DNA using a quantitative real-time polymerase chain reaction (PCR)
      assay for the omp1 gene and for the expression of C. trachomatis 16S rRNA using a
      1-step, real-time reverse-transcriptase PCR assay. RESULTS: A total of 248 people
      were examined. The prevalence of clinically active trachoma was 16.9%. C.
      trachomatis was detected in 19.8% and 6.8% of subjects by the omp1 and 16S rRNA
      assays, respectively. For subjects with positive results for both tests, the
      number of copies of 16S rRNA was approximately 100-fold greater than the number
      of copies of the omp1 gene. In samples from subjects in whom the omp1 gene was
      detected in the absence of 16S rRNA, typically only a few copies of omp1 were
      present. The expression of 16S rRNA was strongly associated with the presence of
      clinical signs of active trachoma. CONCLUSIONS: The use of 16S rRNA expression
      for the detection of chlamydial metabolic activity appears to usefully
      discriminate established infections from the inoculation of the conjunctiva with
      dead or subviable organisms, which probably occurs frequently in settings in
      which trachoma is endemic. The data support conclusions from primate challenge
      studies that live Chlamydiae species or antigens derived from them are needed to
      provoke the clinical signs of disease.

PMID- 16421790
TI  - Outcome of prosthetic joint infections treated with debridement and retention of
      components.
AB  - BACKGROUND: Debridement and retention of the prosthesis represents an attractive
      surgical modality for treatment of prosthetic joint infection, but risk factors
      for treatment failure require clarification. METHODS: We conducted a
      retrospective cohort analysis of all patients with a prosthetic joint infection
      who were treated with debridement and retention of the prosthesis at the Mayo
      Clinic (Rochester, Minnesota) between 1995 and 1999. RESULTS: Debridement and
      retention of the prosthesis was the initial treatment modality for 99 episodes of
      prosthetic joint infection that occurred in 91 patients who presented to the Mayo
      Clinic during 1995-1999. A total of 32% and 23% of all episodes were due to
      Staphylococcus aureus and coagulase-negative staphylococci, respectively. The
      median duration of intravenous antimicrobial therapy was 28 days (range, 1-90
      days). Oral antimicrobial suppression was used in 89% of the episodes, for a
      median duration of 541 days (range, 5-2673 days). Treatment failure occurred in
      53 episodes during a median follow-up period of 700 days (range, 1-2779 days).
      The 2-year survival rate free of treatment failure was 60% (95% confidence
      interval [CI], 50%-71%). Variables associated with an increased risk of treatment
      failure in multivariable analysis included the presence of a sinus tract (hazard
      ratio, 2.84; 95% CI, 1.48-5.44; P = .002) and a duration of symptoms prior to
      debridement of > or = 8 days (hazard ratio, 1.77; 95% CI, 1.02-3.07; P = .04).
      CONCLUSIONS: Debridement and retention of the prosthesis is a common surgical
      modality at our institution to treat prosthetic joint infection. Risk factors
      independently associated with treatment failure include the presence of a sinus
      tract and duration of symptoms prior to debridement of > or = 8 days.

PMID- 16421791
TI  - The evolution and evaluation of a whole blood polymerase chain reaction assay for
      the detection of invasive aspergillosis in hematology patients in a routine
      clinical setting.
AB  - BACKGROUND: Invasive aspergillosis (IA) is associated with high mortality.
      Successful outcome with treatment is linked to early diagnosis. The utility of
      classic diagnostic methods, however, is limited. METHODS: To aid in the diagnosis
      of IA, we retrospectively assessed our diagnostic service, using real-time
      polymerase chain reaction (PCR) and galactomannan sandwich enzyme-linked
      immunosorbent assay (ELISA). RESULTS: A total of 203 patients at risk of invasive
      fungal infection were screened by PCR, and 116 of the patients were also tested
      by ELISA. The patient group comprised 176 patients with hematological malignancy
      and 28 control patients with evidence of invasive candidal infection. Consensus
      European Organisation for Research and Treatment of Cancer and Mycoses Study
      Group criteria were used to classify fungal infection, which, by definition,
      excluded the PCR result. The PCR method was sensitive (up to 92.3% sensitivity)
      and specific (up to 94.6% specificity) and had good agreement with the
      galactomannan ELISA (76.7%) and high-resolution computed tomography scan results.
      CONCLUSIONS: A negative PCR result can be used to rule out IA and to limit the
      need for empirical antifungal therapy; thus, it has a role in diagnosing IA
      infections, especially in combination with antigen testing. PCR-positive cases
      classified as "false positives" regularly reflect the limitations of classic
      microbiological procedures or restricted use of consensus clinical methods
      employed to classify infection.

PMID- 16421792
TI  - Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer
      but still a ways to go.

PMID- 16421793
TI  - Hepatitis A virus infections in travelers, 1988-2004.
AB  - BACKGROUND: Uncertainty exists about the current risk of hepatitis A virus
      infection in nonimmune travelers to destinations with high or intermediate risk
      of transmission. We analyzed recent epidemiological data on imported hepatitis A
      to determine region-specific attack rates and incidences. METHODS: Surveillance
      data on hepatitis A virus infections diagnosed during 1988-2004 were evaluated on
      the basis of notification by laboratories, additional reports of physicians, and
      traveler's statistics. This study focuses on international travelers with
      hepatitis A virus infection detected after their return to Switzerland. RESULTS:
      The rate of imported hepatitis A virus infections decreased 75% from 1988 to 2004
      and accounted overall for 42% of all hepatitis A cases reported in Switzerland.
      The actual incidence of hepatitis A in travelers to countries of high or
      intermediate risk of transmission was 3.0-11.0 per 100,000 person-months abroad
      for all travelers and 6.0-28.0 per 100,000 for those presumed to be nonimmune.
      The actual proportion of those visiting friends and relatives among patients with
      hepatitis A has increased to 28.2%, with children aged 0-14 years predominating.
      Reductions in the incidence by hepatitis A vaccination were estimated to vary
      between 35.0% and 61.8% for different destinations. CONCLUSIONS: The risk of
      hepatitis A virus infections has decreased by a factor of 10-50-fold over time,
      compared with findings from older studies. The risk, however, remains very
      considerable at many destinations, including frequently visited places, such as
      Mexico. Children of immigrants are a high-risk population. Strategies are needed
      to reach those at highest risk.

PMID- 16421794
TI  - Foodborne bacterial infection and hospitalization: a registry-based study.
AB  - BACKGROUND: Foodborne bacterial gastrointestinal infections are important causes
      of morbidity and mortality worldwide, and despite successful control programs in
      some developed countries, these infections continue to have a major impact on
      public health and economy. METHODS: On the basis of data from 3 national
      registries, we determined short- and long-term risks of hospitalization due to
      gastroenteritis, short-term complications, and long-term sequelae after
      infections with nontyphoid Salmonella enterica, Campylobacter species, Yersinia
      enterocolitica, diarrheagenic Escherichia coli, and Shigella species. RESULTS:
      Among 52,121 patients, 7524 (14.4%) were hospitalized with a diagnosis of
      gastroenteritis within 90 days after microbiological diagnosis. A total of 4941
      patients (17.7%) with infections due to S. enterica and 1937 (10.8%) with
      infections due to Campylobacter species were admitted to the hospital.
      Complications, such as gastrointestinal perforation and invasive illness,
      occurred in 647 patients (1.2%). The risk of invasive illness was > 6-fold higher
      in patients with infections due to S. enterica (odds ratio [OR] compared with the
      general population, 30.3; 95% confidence interval [CI], 26.2-35.1) than in those
      with infections due to Campylobacter species (OR, 4.9; 95% CI, 3.5-6.8) (P <
      .001). Long-term sequelae were seen in 865 patients (1.7%). Among 1000 patients
      with infections due to S. enterica, 1820 days of hospital stay were attributable
      to gastroenteritis, complications, and long-term sequelae. The corresponding
      figure for Campylobacter infections was 714 days. CONCLUSIONS: Infections with
      bacteria that are usually foodborne cause considerable morbidity, in terms of
      severe gastroenteritis that requires admission to hospital, as well as
      complications and long-term sequelae. The risk of complications and sequelae
      depends on bacterial species, and nontyphoid Salmonella is particularly
      associated with a burden of severe morbidity.

PMID- 16421795
TI  - Immunotherapy for fungal infections.
AB  - Opportunistic fungal infections are major causes of morbidity and mortality among
      immunocompromised individuals. Fungi have evolved complex and coordinated
      mechanisms to survive in the environment and in the mammalian host. Fungi must
      adapt to "stressors" in the host (including scarcity of nutrients, pH, and
      reactive oxygen and nitrogen intermediates) in addition to evading host immunity.
      Knowledge of the immunopathogenesis of fungal infections has paved the way to
      promising strategies for immunotherapy. These include strategies that increase
      phagocyte number, activate innate host defense pathways in phagocytes and
      dendritic cells, and stimulate antigen-specific immunity (e.g., vaccines).
      Immunotherapy must be tailored to specific immunocompromised states. Challenges
      exist in bringing promising immunotherapies from the laboratory to clinical
      trials.

PMID- 16421796
TI  - Viral pneumonia in older adults.
AB  - Viruses account for a substantial portion of respiratory illnesses, including
      pneumonia, in the elderly population. Presently, influenza virus A H3N2 and
      respiratory syncytial virus are the most commonly identified viral pathogens in
      older adults with viral pneumonia. As diagnostic tests such as reverse
      transcription polymerase chain reaction become more widely used, the relative
      importance of additional viruses (such as parainfluenza, rhinoviruses,
      coronaviruses, and human metapneumovirus) will likely increase. Influenza virus
      should be considered as a cause of pneumonia during the winter months, especially
      during periods of peak activity. Patients with high-grade fever, myalgias, and
      cough should arouse the highest suspicion. Respiratory syncytial virus pneumonia
      should also be suspected during the winter in patients with coryza, wheezing, low
      grade fever, and patchy infiltrates, especially if negative for influenza on
      rapid testing. Because clinical features and periods of activity for many viruses
      overlap, laboratory confirmation of influenza is recommended for cases involving
      seriously ill or institutionalized patients.

PMID- 16421797
TI  - The crisis of resistance: identifying drug exposures to suppress amplification of
      resistant mutant subpopulations.
AB  - Antibiotic resistance is seen in both the hospital and community settings.
      Approaches are required to minimize the increase in resistant strains, such as
      good antibiotic stewardship and the limiting of antibiotic use to appropriate
      circumstances. There are instances when drug dose and/or schedule can be used to
      minimize the probability that mutants will take over the bacterial population.
      Over the past several years, significant advances have been made in understanding
      the relationship between drug concentrations and amplification of resistant
      mutant subpopulations. In this review, we examine the use of preclinical models
      for facilitating this understanding. We also use mathematical techniques,
      including Monte Carlo simulation, to bridge between the identification of
      exposures to minimize resistance and the examination of candidate drug doses to
      achieve this end. Examples are provided for Pseudomonas aeruginosa, Streptococcus
      pneumoniae, Staphylococcus aureus, and Mycobacterium tuberculosis. In each
      instance, quinolone antimicrobials were examined. More investigations with other
      pathogens and drug classes are required.

PMID- 16421798
TI  - Risk assessment and treatment of low-risk patients with febrile neutropenia.
AB  - Progress has been made in the development and validation of rules that attempt
      ito predict a low risk (<10%) of severe infection or clinical complications in
      patients with cancer, fever, and neutropenia. It is uncertain, however, which
      model is optimal, with respect to test characteristics, applicability, and
      interinstitutional reliability, and prospective model validation in a multicenter
      context among outpatients has not been performed. Clinical criteria, such as
      comorbidities and performance status, remain critical in the risk-assessment
      process and probably are used by most physicians caring for patients with cancer
      who are febrile and neutropenic. Clinical prediction rules might be improved in
      the future by including measurements of inflammatory markers, such as
      procalcitonin. Reliable prediction of the risk of medical complications may be
      relevant for decisions regarding parenteral versus oral antimicrobial therapy,
      but it is definitely needed for decisions regarding site of care. Site-of-care
      decisions require thorough assessment not only of medical criteria, but also of
      psychosocial and organizational and/or logistic criteria. If the appropriate
      infrastructure to provide follow-up is available, home-based therapy with oral
      (or parenteral) antibiotics is an acceptable option in the care of patients with
      cancer who have intercurrent febrile neutropenia and a predicted low risk for
      medical complications.

PMID- 16421799
TI  - Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders.
AB  - Rifaximin, a virtually nonabsorbed (<0.4%) rifamycin drug, has in vitro activity
      against aerobic and anaerobic gram-positive and gram-negative microorganisms.
      Because rifaximin is nonabsorbed, systemic adverse effects are unusual, and after
      3 days of therapy, the fecal level of the drug reaches 8000 microg/g. Moreover,
      the important selection of resistant mutants by the related drug, rifampin, has
      not yet been observed for rifaximin. Rifaximin has been demonstrated to reduce
      the duration of traveler's diarrhea secondary to noninvasive bacterial pathogens
      and recently has been shown to reduce the occurrence of the disease when used for
      chemoprophylaxis. Preliminary studies have demonstrated its potential for the
      treatment of other gastrointestinal disorders, such as hepatic encephalopathy.
      Additional studies should be performed to further define the role of rifaximin in
      the treatment of gastrointestinal diseases in adults and children.

PMID- 16421800
TI  - Bacille Calmette-Guerin vaccine-induced disease in HIV-infected and HIV
      uninfected children.
AB  - BACKGROUND: Bacille Calmette-Guerin (BCG)--a live, attenuated vaccine--is
      routinely given to neonates in settings where tuberculosis is endemic,
      irrespective of human immunodeficiency virus (HIV) exposure. HIV-infected infants
      and other immunodeficient infants are at risk of BCG-related complications. We
      report the presentation, treatment, and mortality of children who develop BCG
      disease, with emphasis on HIV-infected children. In addition, we present a
      revised classification of BCG disease in children and propose standard diagnostic
      and management guidelines. METHODS: This retrospective, hospital-based study was
      conducted in the Western Cape Province, South Africa. Mycobacterium tuberculosis
      complex isolates recovered from children aged <13 years during the period of
      August 2002 through January 2005 were speciated by polymerase chain reaction to
      confirm Mycobacterium bovis BCG. Clinical data were collected through medical
      file review. BCG disease was classified according to standard and revised disease
      classifications. Mortality was assessed at the end of the study period. RESULTS:
      BCG disease was diagnosed in 25 children; 22 (88%) had local disease, and 8 (32%)
      had distant or disseminated disease; 5 children (20%) had both local and distant
      or disseminated disease. Seventeen children were HIV infected; 2 children had
      other immunodeficiencies. All 8 children with distant or disseminated disease
      were immunodeficient; 6 were HIV infected. The mortality rate was 75% for
      children with distant or disseminated disease. CONCLUSIONS: BCG vaccination poses
      a risk to infants perinatally infected with HIV and to other primary
      immunodeficient children. The proposed pediatric BCG disease classification
      reflects clinically relevant disease categories in HIV-infected children. The
      suggested diagnostic and treatment guidelines should improve existing case
      management and surveillance. Prospective evaluation of management strategies for
      BCG disease in HIV-infected and HIV-uninfected children is essential.

PMID- 16421801
TI  - Routine childhood bacille Calmette Guerin immunization and HIV infection.

PMID- 16421802
TI  - Accuracy of Papanicolaou test among HIV-infected women.
AB  - OBJECTIVE: We examined the accuracy of the Papanicolaou (Pap) test among women
      with and women at high risk for human immunodeficiency virus (HIV) infection.
      METHODS: Pap test results and colposcopy findings were compared for 189 HIV
      infected women and 95 HIV-uninfected women from the Baltimore HIV Epidemiology
      Research (HER) study site who were followed up semiannually from 1993 through
      1999. Correlations were examined using data from individual visits that were
      analyzed using generalized estimating equation methods. RESULTS: Among women with
      normal results of Pap tests who underwent biopsy, the likelihood of cervical
      intraepithelial neoplasia was significantly greater for HIV-infected women
      (14.3%) than for HIV-uninfected women (1.2%) (P < .01). The specificity and
      negative predictive value of Pap testing were higher among HIV-uninfected women,
      regardless of whether detection of atypical squamous cells of undetermined
      significance was considered to be abnormal. Independent predictors of discordant
      cytologic and histologic findings included detection of human papillomavirus
      (adjusted odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8) and a CD4
      cell count of < 500 cells/microL (adjusted OR, 6.5; 95% CI, 1.5-29.2). Of the 19
      HIV-infected women with normal cytologic findings and cervical intraepithelial
      neoplasia, 18 had abnormal Pap test findings (most often atypical squamous cells
      of undetermined significance) within 1 year of discordant cytologic and
      histologic findings. CONCLUSION: In this well-described cohort of women with and
      women at high risk for HIV infection, agreement between cytologic findings and
      colposcopic and histologic findings was high. A small number of HIV-infected
      women had cervical intraepithelial neoplasia, despite having normal cytologic
      findings; 95% of these women would have had cytologic abnormalities detected
      within 1 year of the discordant results by use of current guidelines for Pap test
      screening. These data fail to support the need for routine colposcopy in all HIV
      infected women.

PMID- 16421803
TI  - Voluntary counseling and testing by nurse counselors: what is the role of routine
      repeated testing after a negative result?
AB  - Three hundred eighty-eight human immunodeficiency virus (HIV)-negative clients in
      Zimbabwe were retested at 3 months using 2 parallel rapid tests. One operator
      error (risk, 0.26%; 95% confidence interval, 0.0065%-1.4%) and no "true"
      seroconversions (upper 95% confidence limit, 0.96%) were detected. High-risk
      behavior was not significantly reduced. Policies recommending routine retesting
      need to be reconsidered.

PMID- 16421804
TI  - Safety of aseptically processed allograft tissue.

PMID- 16421805
TI  - Imiquimod 5% cream for the treatment of recurrent, acyclovir-resistant genital
      herpes.

PMID- 16421807
TI  - Gram-negative bacterial surgical site infection and intensive care unit patients.

PMID- 16421809
TI  - Kikuchi's disease or Kikuchi's syndrome?

PMID- 16421811
TI  - Lyme-like illness currently deserves Lyme-like treatment.

PMID- 16421813
TI  - Pneumocystis jiroveci dihydropteroate synthase gene mutations at codon 171 but
      not at codons 55 or 57 detected in Germany.

PMID- 16421814
TI  - Clinical significance of occult hepatitis B virus infection cannot be overlooked.

PMID- 16421817
TI  - Paradigm lost.

PMID- 16421815
TI  - Noninvasive diagnosis of mitochondrial dysfunction in HAART-related
      hyperlactatemia.

PMID- 16421818
TI  - Plans and hopes for veterinary education in Mexico.

PMID- 16421819
TI  - Evidence-informed education in the health care science professions.
AB  - The use of evidence to inform the practice and policy of professional education
      in the health care sciences is taking on an increasingly important role alongside
      the use of more traditional types of knowledge. It is an addition to the
      repertoire in this and many professions that draw on social-science discipline
      knowledge. In the field of health care science professional education, the Best
      Evidence Medical Education Collaboration (BEME) leads the movement toward
      evidence-informed practice. It is a movement not without controversy, and lively
      debate on epistemological and practical issues is in progress. With publication
      of the first BEME Reviews in 2005, this debate will be extended. We can expect
      energetic and healthy commentaries on both the review process and the substantive
      findings. All this will make a valuable contribution to an important aspect of
      professional education practice and policy that is here to stay.

PMID- 16421820
TI  - Retention of surgery specialists in academia: a critical agenda.
AB  - Recruitment and retention of specialists to academia appears to be a growing
      problem in university teaching hospitals. Members of the American College of
      Veterinary Surgeons (ACVS) believe that the movement of surgery specialists to
      practice may have an impact on the training of veterinary students and surgery
      residents. To address these concerns, 1,071 ACVS diplomates and 60 department
      heads and hospital directors from all veterinary schools in North America were
      surveyed to determine whether a problem exists, the extent of the problem, and
      potential reasons for migration of specialists to practice. Responses were
      obtained from 620 ACVS diplomates (58 per cent) and 38 department heads and
      hospital directors (63%) from 28 different universities. The responses confirmed
      a net movement of surgery specialists from academia to practice. Eighty seven
      percent of department heads and hospital directors believed there was a shortage
      of small animal surgery specialists in academia; this information was supported
      by the fact that 47% responded that they had open positions and 68% had
      difficulty filling positions in the last five years. The demand was slightly less
      for large animal surgery specialists, and 42 per cent of respondents indicated
      that they had open positions. Financial considerations were the most common
      reason for surgery specialists to move from academia to private practice. Seventy
      six percent of responding ACVS diplomates in private practice had a total
      compensation package valued at greater than $125,000 per year, whereas 77.8% of
      diplomates in academia had total compensation valued at $125,000 or less. Most
      universities offer starting salaries (not including benefits) for recently
      certified surgery specialists ranging from $70,000 to $90,000. Reasons for moving
      from academia to practice besides financial considerations included undesirable
      location of university hospitals; lack of interest in research; and a belief that
      university administration was not supportive of surgery specialists. Many
      academic surgery specialists were frustrated by the requirement for productivity
      in research, teaching, and service for promotion in tenure-track positions.

PMID- 16421821
TI  - Why the theme animal welfare?

PMID- 16421822
TI  - Introduction: animal welfare education, a critical time in veterinary medicine.

PMID- 16421823
TI  - Approaches to teaching animal welfare at 13 veterinary schools worldwide.
AB  - This paper comprises brief descriptions by faculty at 13 veterinary schools in
      Europe, North America, South America, and Australasia that summarize
      undergraduate training in animal welfare at the respective schools and how
      students are assessed.

PMID- 16421824
TI  - Animal welfare education: development and prospects.
AB  - Animal welfare has developed rapidly as a scientific discipline since the 1980s.
      Concepts have been refined, methodologies for assessment developed, and links
      made to other areas of science. Changes in the subject and in its teaching are
      required. Since 1986, a series of senior academic teaching posts in the subject
      have been created, especially in the last 10 years. Veterinary and animal science
      students should receive a specific course on animal welfare, in addition to
      mention of the subject in other courses. In the future, more allusion to
      developments in understanding of welfare in relation to disease and brain
      measures of welfare is likely. The central role of animal welfare in veterinary
      and animal science teaching will become more firmly established.

PMID- 16421826
TI  - Animal welfare training at the Ontario Veterinary College.
AB  - The University of Guelph is internationally recognized as a leader in animal
      welfare and is home to the Colonel K.L. Campbell Centre for the Study of Animal
      Welfare and to numerous faculty with expertise in the discipline. However, while
      animal welfare receives significant attention within the agricultural college,
      its didactic teaching within the veterinary curriculum has been limited.
      Veterinary students receive four hours of instruction in animal ethics and apply
      their knowledge within the communication lectures and laboratories, totaling 11
      15 hrs. Compulsory coursework explicitly addressing factual components of animal
      welfare science, welfare assessment, and associated animal-related policy
      constitute only 12 hrs throughout the four-year Doctor of Veterinary Medicine
      curriculum. However, an elective final-year clinical rotation and a graduate
      course specific to animal welfare were offered for the first time in 2004/2005.
      Student interest in animal welfare is evident through their participation in
      summer research projects in animal welfare, an animal welfare mentor group, and a
      student-run animal welfare club that organizes an Animal Welfare Forum each
      October. Veterinarians have important contributions to make in decision making
      about animal welfare issues, at clinician and policy levels. Although motivated
      individuals can seek out opportunities to expand their knowledge of animal
      welfare, a compulsory senior-level course in animal welfare is needed to develop
      the necessary depth of understanding of this discipline if veterinarians, as a
      profession, are to meet society's expectations about animal welfare.

PMID- 16421825
TI  - Teaching animal welfare at the University of Sydney's Faculty of Veterinary
      Science.
AB  - Animal welfare is part of the Mission Statement of the Faculty of Veterinary
      Science at the University of Sydney and is taught throughout the undergraduate
      curriculum. Two units of study have a particular focus on animal welfare:
      Professional Practice in years 1, 2, and 3 and Animal Behaviour and Animal
      Welfare Science in year 3. There is an emphasis on the refinement and development
      of alternatives to the use of animals in teaching. With a conscientious objection
      policy in place, these elements of our approach demonstrate the increasing
      importance of ethical teaching in the faculty. Undergraduate students have
      recently founded a vibrant special interest group called Veterinary Students for
      Animal Welfare. The faculty is advised on matters relating to animal welfare by
      its Animal Welfare Advisory Committee, chaired by the Sub-Dean for Animal
      Welfare. With the development of a Faculty Animal Welfare Policy, the faculty is
      progressing to a more proactive and public profile on animal welfare issues.

PMID- 16421827
TI  - "Concepts in animal welfare": a syllabus in animal welfare science and ethics for
      veterinary schools.
AB  - Public attitudes toward animal welfare have improved with growing social
      affluence, and veterinarians are increasingly expected to be informed about
      animal welfare in a broader sense than health alone. However, animal welfare has
      not been a traditional component of the veterinary curriculum. To help address
      this lack, the World Society for the Protection of Animals(WSPA) and the
      University of Bristol School of Veterinary Science launched the ''Concepts in
      Animal Welfare'' syllabus in 2003. This comprehensive syllabus comprises seven
      core and 23 elective modules and covers a range of animal welfare issues,
      including farm and companion animal welfare, wildlife, and the use of animals in
      experiments. There are also modules on ethics and animal legislation. The
      syllabus is interactive, promotes critical analysis of issues from different
      angles, and may be adapted for use in any veterinary curriculum. WSPA provides
      training and workshops in developing countries and assists with the
      implementation of the syllabus.

PMID- 16421828
TI  - Towards a humane veterinary education.
AB  - There is a vast array of learning tools and approaches to veterinary education,
      many tried and true, many innovative and with potential. Such new methods have
      come about partly from an increasing demand from both students and teachers to
      avoid methods of teaching and training that harm animals. The aim is to create
      the best quality education, ideally supported by validation of the efficacy of
      particular educational tools and approaches, while ensuring that animals are not
      used harmfully and that respect for animal life is engendered within the student.
      In this paper, we review tools and approaches that can be used in the teaching of
      veterinary students, tools and approaches that ensure the dignity and humane
      treatment of animals that all teachers and students must observe as the very
      ethos of the veterinary profession that they serve. Veterinary education has not
      always met, and still often does not meet, this essential criterion.

PMID- 16421829
TI  - Effective use of simulations for the teaching and acquisition of veterinary
      professional and clinical skills.
AB  - Simulation technology will feature prominently in this exciting, yet challenging,
      time for veterinary medicine. The profession is evolving to keep pace with rapid
      changes in clinical practice, scientific discovery, and educational strategy,
      while ensuring that it follows the public mandate to produce competent
      veterinarians. Among the challenges to meeting this educational goal are
      limitations-due to important issues such as animal welfare-on the availability of
      real patients for training. Drawing chiefly on the experience in human medicine,
      this article explores the use of simulations in veterinary medical education to
      provide safe and ethical alternative opportunities for learners to practice
      essential clinical and professional skills.

PMID- 16421830
TI  - Effective bibliographic searching for animal alternatives in veterinary medical
      education: the UC Davis web site.
AB  - To prepare students in just four years to enter veterinary practice, veterinary
      medical educators offer an array of laboratory and clinical experiences
      coordinated with didactic instruction. Recent curricular changes have reduced the
      numbers of animals involved in painful or terminal procedures. For each use of
      animals, veterinary educators are required by the USDA's policies 11 and 12 to
      complete animal-use protocols that include questions on alternatives to
      procedures causing more than momentary pain or distress. Veterinary medical
      educators seeking improved teaching resources and methods or completing animal
      use protocols may find it frustrating to locate the relevant information, which
      is dispersed across many databases. This paper addresses a gap facing veterinary
      educators by presenting user-friendly searching tools that are targeted toward
      (a) locating teaching resources and (b) conducting effective bibliographic
      searches on standard teaching laboratory procedures, as required for animal-use
      protocols. These tools simplify searching by providing streamlined access to the
      resources being sought. Facilitating efficient and effective searching by users
      can improve teaching and simplify compliance with USDA requirements.

PMID- 16421831
TI  - Mainstreaming alternatives in veterinary medical education: resource development
      and curricular reform.
AB  - Veterinary medical educators are charged with preparing students to enter
      practice in veterinary medicine during a four-year, intensive, professional
      education program. This requires giving students in laboratory training that
      involves dead, anesthetized, or conscious animals, so that they become proficient
      in the expected range of veterinary knowledge, skills, and abilities. Undeniably,
      experience with animals is essential to prepare students for a profession in
      which animals comprise the total domain. However, the consumptive use of animals
      for teaching students, especially in laboratories, is increasingly subject to
      regulatory requirements, while also being scrutinized by animal protection
      groups, and has become a common focus of contention among veterinary students.
      Not surprisingly, the use of animals in teaching has sharply declined over the
      past few decades, as new teaching resources and methods, involving less
      consumptive use of animals, have been incorporated. This change in veterinary
      medical education has occurred on such a wide scale, in almost all veterinary
      schools and colleges, that the educational approach can serve as a model for
      further developments within the veterinary educational community and, indeed, for
      animal-related material in secondary schools and undergraduate higher education.
      This article highlights examples of the leadership provided by veterinary
      educators in developing alternative teaching resources and methods, while
      maintaining the high level of proficiency expected from traditional educational
      approaches.

PMID- 16421832
TI  - Attitudes of veterinary students at one US college toward factors relating to
      farm animal welfare.
AB  - RATIONALE FOR STUDY: The American Veterinary Medical Association's policy states
      that veterinarians are obliged to promote good animal welfare. In order to
      establish how compatible the attitudes of future veterinarians in one North
      American Veterinary College were with the promotion of good animal welfare,
      students were surveyed with respect to their opinions about the humaneness of
      commonly employed agricultural procedures (e.g., hot branding) and their beliefs
      about the cognitive ability of various domesticated species. METHODOLOGY: A Web
      based questionnaire was made available to all veterinary students at Cornell
      University. Descriptive summary data were collected with regards to students'
      perceptions of the cognitive abilities of six different domesticated species.
      Students were also asked if they considered certain agricultural procedures to be
      humane for each of these species. The data were analyzed with respect to
      students' future career goals. Chi-squared tests and nonparametric statistical
      techniques were used to examine differences between species and desired career
      goals. RESULTS AND CONCLUSIONS: Veterinary students were more likely to believe
      that dogs and cats had cognitive abilities than farm animals did. Students
      considered various procedures to be more humane for farm mammals than for dogs
      and cats. Students aspiring to work with food animals considered more procedures
      to be humane for all species than did students aspiring to work with small
      animals. The inconsistency of students' attitudes for different species has
      implications for veterinary education and animal welfare. Scientific fields
      integral to understanding animal welfare may need to be emphasized within the
      veterinary educational curriculum.

PMID- 16421833
TI  - Factors influencing veterinary students career choices and attitudes to animals.
AB  - The purpose of the study was to investigate the influence of demographic and
      experiential factors on first-year veterinary students career choices and
      attitudes to animal welfare/rights. The study surveyed 329 first-year veterinary
      students to determine the influence of demographic factors, farm experience, and
      developmental exposure to different categories of animals on their career
      preferences and on their attitudes to specific areas of animal welfare and/or
      rights. A significant male gender bias toward food-animal practice was found, and
      prior experience with particular types of animals--companion animals, equines,
      food animals--tended to predict career preferences. Female veterinary students
      displayed greater concern for possible instances of animal suffering than males,
      and prior experience with different animals, as well as rural background and farm
      experience, were also associated with attitude differences. Seventy-two percent
      of students also reported that their interactions with animals (especially pets)
      had strongly influenced the development of their values. Animals ranked second in
      importance after parents in this respect. The present findings illustrate the
      importance to issues of animal welfare of the cultural context of past experience
      and influences on attitude development. The results also suggest that previous
      interactions with animals play a critical role in guiding veterinary students
      into their chosen career, as well as in helping to determine their specific
      employment preferences within the veterinary profession. From an animal welfare
      perspective, the dearth of women choosing careers in food-animal practice is a
      source of concern.

PMID- 16421835
TI  - Teaching animal welfare science, ethics, and law to veterinary students in the
      United kingdom.
AB  - Teaching veterinary students about animal welfare science, ethics, and law has
      been identified as a priority of the veterinary curriculum. Suggested content for
      such a course, the stage at which it should be taught, and possible methods of
      teaching and assessing the subject have been outlined. Critically, such a course
      needs to address the quantification of the impact of humans on animals (welfare
      science), the analysis of our moral obligations (welfare ethics), and knowledge
      of minimum welfare standards (welfare legislation). A mixture of both teaching
      methods and assessment techniques is needed to ensure that sufficient skills and
      knowledge and a deeper understanding are achieved.

PMID- 16421834
TI  - Integrating animal welfare into veterinary education: using an online,
      interactive course.
AB  - Veterinarians in the United States and abroad are faced with growing public
      concern for the welfare of animals, particularly those in production. To prepare
      veterinarians to exert the leadership expected by the public and industry, steps
      should be taken to provide instruction in animal welfare at veterinary colleges.
      The ultimate goal is to offer courses in animal welfare in a consistent manner on
      a global scale, utilizing existing expertise in an efficient and cost-effective
      manner. Given the intense curricula of veterinary schools and the scarcity of
      instructors trained in animal welfare, a nontraditional approach is needed to
      educate veterinary students in the United States and abroad in animal welfare.
      Michigan State University (MSU) is developing a graduate-level, online
      interactive course in animal welfare assessment. The course will approach the
      topic of animal welfare education from a holistic, multidisciplinary standpoint
      (encompassing ethics, economics, and behavior) and address issues important to
      the general public and the international community. The MSU course will draw on
      renowned international animal welfare experts, allowing students to receive high
      quality education that would be difficult in any other circumstance. The course
      will bridge an important gap in the veterinary curriculum and offer a complete
      and congruous education in animal welfare to veterinarians worldwide. The MSU
      course will also serve as a model for collaboration in content assembly and
      course delivery, by using technology to leverage global expertise in the
      interests of educational equity. In addition to innovative technology, such as
      the use of Web-collaboration software to create the course, a variety of media
      that enable students to interact with the material will also be incorporated
      throughout the course. Thus, the course will not only utilize the Internet to
      provide access to high-quality material, but will also require the active
      participation of the student, which is needed for effective learning.

PMID- 16421836
TI  - Commentary: a veterinary practitioner's perspective--the necessity of animal
      welfare expertise in today's job market.

PMID- 16421837
TI  - Evaluation of student attitudes to cooperative learning in undergraduate
      veterinary medicine.
AB  - RATIONALE FOR THE STUDY: Recent studies have demonstrated that collaborative or
      cooperative learning (CL) provides students and teachers with a variety of
      advantages over traditional instructional methods. To explore the possibility of
      introducing CL into the veterinary undergraduate curriculum on a larger scale-to
      facilitate the development of professional competencies-a cooperative learning
      assignment (CLA) was introduced into the fourth year Bachelor of Veterinary
      Medicine and Surgery (BVMS) degree course at the University of Glasgow. An
      evaluation was carried out as a basis for optimizing subsequent CL activities in
      the undergraduate course. METHODOLOGY: Evaluation of student attitudes to the CLA
      was conducted using pre- and post-task questionnaires and a focusgroup discussion
      involving student representatives from several of the small groups. Quantitative
      questionnaire data were imported into SPSS and a statistical test was used to
      identify any significant shifts in student attitudes. RESULTS AND CONCLUSIONS:
      Analysis of the quantitative questionnaire results indicates that students-who
      regarded themselves generally as team players rather than competing individuals
      had few concerns before or after the CLA. There were some significant shifts
      (negative and positive) in response to some of the questions, but generally the
      results were encouraging. However, a number of issues emerged from the focus
      group discussion with regards to the administration of CL and matching students'
      expectations to their experiences. In particular, students need to be adequately
      informed at the outset about the CL process and about how it will be assessed,
      have access to the required facilities, and be comfortable with learning
      different skills sets from those their peers are learning. Staff facilitators
      require adequate guidance on what they are expected to contribute to the CL
      process.

PMID- 16421839
TI  - Perceptions of the human-animal bond in veterinary education of veterinarians in
      Washington State: structured versus experiential learning.
AB  - RATIONALE FOR THE STUDY: The purpose of this research was to describe Washington
      private practitioners' beliefs about how the Human-Animal Bond (HAB) should be
      addressed in DVM curricula and continuing education. METHODOLOGY: 1,602
      Washington veterinarians in private practice were asked to participate in an
      online survey that addressed the importance of HAB and of DVM/post-DVM HAB
      education. RESULTS AND CONCLUSIONS: The response rate was 25.9% (415/1,602).
      Eighty-one percent (334/412) of respondents indicated that the HAB was important
      to their decisions to become veterinarians. The HAB was more important to the
      most recent graduates than to earliest graduates and to females than to males.
      Forty-four percent (184/415) of respondents considered mentoring to be the best
      way to learn about the HAB while in veterinary school. Of the 40% (165/415) of
      respondents who indicated that their veterinary schools offered structured
      learning on the HAB, 89% (145/163) said they had participated in it. Seven
      percent (29/415) indicated that entry-level veterinarians were very prepared to
      identify and facilitate the HAB, while 54% (224/415) said that they were somewhat
      prepared. Only 32% (131/415) had participated in any HAB structured learning
      since having started practicing, and the earliest graduates were twice as likely
      to have participated as the most recent graduates. More than half (55%, 223/407)
      disagreed or strongly disagreed that post-DVM, the best way to learn about the
      HAB is through structured learning. However, 83% (342/414) agreed that continuing
      education credits should be given for HAB classes. Eighty-six percent (358/414)
      supported additional HAB research. Ninety-seven percent (402/414) agreed that the
      best way to learn about the HAB is through experience. These results suggest that
      veterinarians do not value HAB structured learning as much as experiential
      learning and that they are not very confident in recent graduates' abilities
      regarding the HAB. We propose HAB structured learning in the first three years of
      DVM education, complemented by the incorporation of the HAB into clinical
      rotations and post-DVM continuing education.

PMID- 16421838
TI  - Pre-matriculation indicators of academic difficulty during veterinary school.
AB  - The purpose of this study was to assess pre-matriculation academic and
      demographic data to identify risk factors for academic difficulty and failure to
      graduate among veterinary students. Admissions data were compiled for 1,098
      students admitted to veterinary college between 1989 and 2000 inclusive. Students
      were classified by (a) academic success, consisting of students who completed
      veterinary school within four years in the top 90% of the class or (b) academic
      difficulty, including students dismissed for academic reasons, students who
      experienced academic delay, and students who graduated with a cumulative GPA in
      the 10th percentile of their class. Of 1,098 admitted students, 930 (84.7%)
      completed veterinary school within four years in the top 90% of their class.
      Among students with academic difficulty, 94 (8.6%) completed veterinary school in
      four years in the 10th percentile, 44 (4%) experienced academic delay, and 30
      (2.7%) were dismissed. Academic difficulty was associated with a low prerequisite
      GPA, a low GRE score, poor undergraduate institutional selectivity, and older age
      (> or =35 years). Students who attended three-or-more undergraduate institutions
      or two-year colleges prior to attending a four year institution were 1.9 times
      more likely to experience academic difficulty and 3.87 times more likely to fail
      to graduate than students who attended a four-year institution (major or small)
      to complete their prerequisites. These study findings may assist with early
      identification of students at greater risk of experiencing academic difficulty
      and support the consideration of cognitive selection criteria (GRE and GPA) and
      undergraduate institutional experience during the admissions process.

PMID- 16421840
TI  - A comparison of responses to group learning between first-year Asian and first
      year Australian veterinary science students.
AB  - INTRODUCTION: Group learning has been used to enhance deep (long-term) learning
      and promote life skills, such as decision making, communication, and
      interpersonal skills. However, with increasing multiculturalism in higher
      education, there is little information available as to the acceptance of this
      form of learning by Asian students or as to its value to them. METHODOLOGY: Group
      learning projects, incorporating a seminar presentation, were used in first-year
      veterinary anatomical science classes over two consecutive years (2003 and 2004)
      at the School of Veterinary Science, University of Queensland. Responses of
      Australian and Asian students to survey forms evaluating the learning experience
      were analyzed and compared. RESULTS: All students responded positively to the
      group learning, indicating that it was a useful learning experience and a great
      method for meeting colleagues. There were no significant differences between
      Asian and Australian students in overall responses to the survey evaluating the
      learning experience, except where Asian students responded significantly higher
      than Australian students in identifying specific skills that needed improving.
      CONCLUSIONS: Group learning can be successfully used in multicultural teaching to
      enhance deep learning. This form of learning helps to remove cultural barriers
      and establish a platform for continued successful group learning throughout the
      program.

PMID- 16421841
TI  - Rethinking the learning and evaluation environment of a veterinary course in
      gross anatomy: the implementation of an assessment and development center and an
      E-learning platform.
AB  - Today's students belong to an interactive generation and receive information
      through multiple channels. In addition, veterinary medicine curricula are
      changing due to trends such as student-centered education and competence-based
      learning. In consequence, we were stimulated to rethink the way in which
      veterinary gross anatomy was taught and assessed. As a first step, the learning
      goals for the students participating in the veterinary gross anatomy course were
      clearly defined. Students had to acquire knowledge of and insight into the
      structure, the function, and the interrelationships of gross anatomical
      structures in various species. They also had to be competent in observing,
      palpating, and exposing the anatomical structures. Additionally, they had to
      attain some general skills and attitudes. Next, a learning environment was
      developed enabling students to accomplish these goals. The three main components
      of this new environment were, first, the reorientation of classic cadaveric
      dissections towards attaching an increased importance to the attainment of course
      specific and general skills and attitudes; second, the incorporation of an e
      learning platform; and third, an increase in the number of student-lecturer
      interactions during lecture hours. Finally, the assessment and examination were
      adjusted to complement the goals defined earlier and the redesigned learning
      environment. An assessment and development center (ADC) was introduced, where
      students demonstrated their skills and insights by completing job-relevant
      assignments within a set time limit. This ADC was used as a means of evaluating
      students as well as of giving them feedback. Students were enthusiastic about
      this way of teaching although they experienced it as difficult.

PMID- 16421842
TI  - Genetic susceptibility to scrapie in sheep: a clinically relevant theme in
      veterinary medical education.
AB  - RATIONALE FOR THIS STUDY: This article describes and evaluates two molecular
      biology practical classes based around the theme of genetic susceptibility to
      scrapie in sheep. These practical classes allow students to experience a range of
      molecular biology techniques in the context of a clinically based genetic
      disease. METHODOLOGY: The two molecular biology practical classes described are
      evaluated in terms of their perceived usefulness to study by first-year
      veterinary medicine students. The students' ratings are then assessed in relation
      to the approaches to studying (i.e., deep, strategic, and surface). These
      dimensions of learning are measured using the 52-item Approaches to Studying
      Inventory (ASI). RESULTS: The overall ratings from students in relation to both
      the practical classes were found to be positive. The scrapie genotyping practical
      was the highest-ranking laboratory-based practical in the first-year curriculum.
      Ratings in terms of usefulness to studies for both practical classes were found
      to be significantly higher for students with higher deep learning scores.
      CONCLUSION: The practical classes described here provide a clinically relevant
      scenario within which molecular biology concepts and methods can be illustrated
      to veterinary students. The positive correlation with deep learning is more
      evident for the scrapie genotyping practical than for the DNA extraction
      practical. This may reflects the complexity of the former, which is greater both
      technically and conceptually.

PMID- 16421843
TI  - Listing of inherited disorders in animals (LIDA): an online relational database,
      using non-technical descriptions written by veterinary students.
AB  - This online database uses a search facility that allows users to select from the
      180 recognized dog breeds in Australia and find out which ones are prone to the
      more than 500 inherited disorders on record. It was developed in consultation
      with a number of supporting organizations, including the local breeders'
      governing body and animal-welfare groups, as well as owners. It is hoped that,
      although primarily for veterinary education, the Web site will increase awareness
      among breeders and may encourage them to adopt breeding programs that decrease
      the occurrence of the most prevalent disorders.

PMID- 16421844
TI  - Practice-based education at Michigan State University.
AB  - Practice-based large animal education at Michigan State University (MSU) was
      initiated in 1995. Urbanization of the area surrounding MSU and the declining
      number of livestock and farms to provide clinical experience under field
      conditions were the major reasons for adopting this educational model. Veterinary
      students, as a requirement for graduation from the professional program, must
      successfully complete a three-week clerkship in a private practice that has
      either a food animal or an equine emphasis. The objective of the practice-based
      program is to provide students with introductory on-the-farm experience, with
      emphasis on examination, diagnosis, treatment, and prevention of common medical
      and surgical conditions of horses and/or food animals. Participating practices
      must be located in Michigan, have a sufficient case load, be interested in
      teaching senior veterinary students, and be willing to interact with the program
      coordinator and attend annual meetings. Sixty-nine practices are currently
      participating. The program coordinator matches students to practices based on the
      students' species interest and background, the personalities of the student and
      practitioner, and any special concerns or needs of the students (health
      conditions, child care). Assessment of students includes a practitioner's
      performance evaluation and review of written assignments (case log, clinical case
      reports, and a practice management assessment report) by campus faculty. A
      pass/no pass grading system is used. Overall, the Practice-Based Ambulatory
      Program represents a successful model for meeting the clerkship objectives.
      Additionally, exposing students to a high volume of commonly encountered
      conditions in a private business setting complements the referral cases seen in
      our large animal teaching hospital.

PMID- 16421845
TI  - One medicine.

PMID- 16421846
TI  - Personality, cognitive adaptation, and marital satisfaction as predictors of well
      being among older married adults.
AB  - The current study examines constructs that contribute to the well-being of an
      international sample of older married adults. A convenience sample of 208
      participants was recruited through an Internet site as well as more traditional
      means such as newspaper advertisements and contact with community groups. The
      resulting structural equation model provides further support for the revised
      theory of cognitive adaptation. Within this model, the direct and indirect
      contributions of personality, marital satisfaction, and cognitive adaptation are
      examined in relation to wellbeing. Contrary to previous findings, personality
      appears to have an indirect effect upon both marital satisfaction and well-being.
      Cognitive adaptation, in contrast, has both a direct and indirect effect upon the
      well-being of older adults. Limitations of use of the Internet as a vehicle for
      data collection are considered as well as directions for future study.

PMID- 16421847
TI  - Patterns of paid and unpaid work: the influence of power, social context, and
      family background.
AB  - Over the last several decades there have been changes in how paid and unpaid
      labour is divided between men and women: The rate of women's participation in the
      labour force women has increased as has men's participation in household labour.
      Although a plethora of research has addressed these changes by analysing couple
      and individual data, few have examined them within the context of multi
      generational families. Using a case study analysis of a three-generation family,
      this paper shows that gender, class, social context, and family background
      influence how paid and unpaid work is divided within families. The case study
      shows that the social context of a given time conditions the options women and
      men have available to them in negotiating the balance of work and family
      responsibilities. Yet within this context, family background also matters.
      Negative childhood experiences were an impetus for adult children negotiating
      patterns of paid and unpaid labour that were different from those of their
      parents.

PMID- 16421848
TI  - Comparison of provincial and territorial legislation governing substitute consent
      for research.
AB  - In Canada, provincial and territorial laws address circumstances in which a
      substitute decision-maker may be appointed for an adult deemed legally incapable
      of making decisions in one or more areas of life. We searched for provincial and
      territorial laws that explicitly address substitute decision-making about
      research participation, and found significant differences among Canadian
      jurisdictions. In some provinces and territories there is no direct statutory
      guidance on the issue. Differences among jurisdictions that address substitute
      decision-making about research in legislation include whether judicial
      intervention is required to authorize the substitute decision-maker, whether any
      advance directive in place must explicitly authorize the decision about research
      in order for a proxy to consent, and how risk and benefit thresholds beyond which
      substitute consent to research is prohibited are articulated. It is imperative
      that government, researchers, and the Canadian public revisit the principles
      underpinning substitute decision-making about research in light of national and
      international norms, in order to lend clarity and consistency to this area of law
      and research practice.

PMID- 16421849
TI  - Translating evidence into practice: the case of dementia guidelines in
      specialized geriatric services.
AB  - This paper describes a process of identifying best practice guidelines for non
      pharmacological management for individuals with dementia and disseminating them
      to a group of frontline practitioners in specialized geriatric services. Our
      dissemination plan involved early participation of practitioners, development of
      a chart summarizing five guidelines showing commonalities, contrasts, and gaps in
      the guidelines, and their interpretation, colour-coded for the strength of the
      evidence on which they were based. Two sequential workshops were held in which
      recommendations for action were developed. Outcomes of the process included a
      resource manual, a network of practitioners, and action recommendations based
      upon survey data. An early follow-up evaluation showed increased adoption of
      guidelines.

PMID- 16421850
TI  - Risk factors for falling among community-dwelling veterans and their caregivers.
AB  - PURPOSE: To assess the prevalence and strength of association of risk factors for
      falling in Canadian veterans of World War II and Korea and their caregivers.
      METHODS: Questionnaires were sent to addresses of 3,000 Canadian veterans
      (response rate(1/4)70%). Risk factors for falls and the frequency of falls and
      injurious falls in the past 12 months were collected. RESULTS: Veterans had more
      risk factors than did caregivers, and more had fallen in the past year (39.8% vs.
      29.7%). Risk factors in the logistic model for veterans included lower extremity
      disability (odds ratio 1.98, 95% confidence interval 1.5-2.6); lower extremity
      weakness (OR 1.75, 95% CI 1.3-2.3); worse memory than peers (OR 1.67, 95% CI 1.1
      2.5); one or more visits to the family doctor in the past month (OR 1.53, 95% CI
      1.2-2.0); and worse memory than 5 years ago (OR 1.36, 95% CI 1.0-1.8).
      CONCLUSIONS: Veterans appear more frail and prone to falling than their
      caregivers.

PMID- 16421851
TI  - [Heterogeneity of cognitive deficits in Alzheimer's and cognition therapy:
      research design ].
AB  - Numerous studies suggest that the clinical presentation of Alzheimer's disease
      (AD) is varied and that AD is thus a heterogeneous disorder. Evidence of this
      inter-individual variability has had an important impact on the approaches to the
      cognitive rehabilitation of AD, particularly in the early stages of the disease.
      Research has shown that, despite variable cognitive profiles, many preserved
      capabilities are observed in the first stages of AD and that the disease does not
      affect all cognitive functions globally. These preserved capabilities make it
      possible to apply cognitive interventions. However, numerous methodological
      difficulties are encountered in evaluating the effectiveness of these
      interventions, many of which are related to the heterogeneity of the deficits.
      The purpose of this article is to discuss this heterogeneity and its impact on
      methodological characteristics, especially participant selection and research
      design.

PMID- 16421852
TI  - The role of social support in the relationship between urinary incontinence and
      psychological distress in older adults.
AB  - While an association between UI and psychological distress among older adults has
      been established in the literature, the mechanisms underlying this relationship
      remain less clear. Using a sample of 4,689 older adults from the Canadian
      Community Health Survey (1.1), we test the potential mediating and moderating
      effects of four dimensions of social support on the UI-distress relationship.
      Incontinent older adults are significantly more likely to report higher levels of
      distress than continent adults. Although we do not find support for a mediating
      effect of any of the dimensions of social support, we do report a significant
      interaction between one dimension of social support (tangible support) and UI. A
      buffering effect of tangible support is evident for continent - but not
      incontinent - respondents. These findings emphasize the need to assess the types
      of social support and the context in which they operate.

PMID- 16421853
TI  - Competence, capacity, and informed consent: beyond the cognitive-competence
      model.
AB  - Only competent persons can give informed consent to health care. Current
      approaches define competence in essentially cognitive terms, thereby ignoring the
      fact that someone may be cognitively competent yet lack the capacity to give a
      valid consent. I outline a more robust theory of competence that includes not
      only cognitive but also emotional and valuational parameters. I then distinguish
      competence from capacity, and indicate the role this distinction can usefully
      play in the extended and continuing care setting. I also show how this
      distinction is consistent with several recent Canadian legal decisions, and
      outline its usefulness in interpreting and applying relevant provincial statutes.

PMID- 16421854
TI  - Patient outcomes after discharge from a geriatric day hospital.
AB  - Evidence suggests that frailer older patients benefit from a continuum of care
      rather than the admit/discharge model of our health system. This study examined
      patient outcomes after discharge from a geriatric day hospital (GDH) to determine
      what proportion continues to do well, what proportion declines, how the two
      groups differ, and if factors predictive of deterioration can be identified.
      Using telephone survey and Goal Attainment Scaling methodologies, the goals of
      151 patients discharged from a GDH between 6 and 18 months previously were
      examined to determine whether GDH achievements were maintained or lost. All but 5
      patients improved between GDH admission and discharge; after discharge, 39 per
      cent deteriorated. The need for more support in the community was predictive of
      deterioration, probably reflecting patient frailty. Number of medical diagnoses
      or medications were not predictive. Frailer older patients tend not to maintain
      goals achieved in a GDH after discharge and may benefit from ongoing maintenance.

PMID- 16421855
TI  - SERRS study of the DNA binding by Ru(II) tris-(Bipyridyl) complexes bearing one
      carboxylic group.
AB  - Surface enhanced resonance Raman scattering (SERRS) is shown to be a satisfying
      method to study the interaction between DNA and ruthenium complexes
      [Ru(bpy)(2)(Hcmbpy)][PF(6)](2), where Hcmbpy = 4-carboxy-4'-methyl-2,2'
      bipyridine. Such metallic complexes are known for their fluorescence properties.
      To validate this spectroscopic approach we have checked that i) at a given
      lambda(ex), silver colloidal SERRS spectra of Ru complexes closely resemble
      resonance Raman spectra in aqueous solutions, intensity excepted, and ii) the DNA
      fragments are not altered when they are adsorbed on the Ag nanoparticles surface.
      This investigation shows that the intensity of the Ru complexes SERRS spectra is
      reduced in the presence of DNA, in particular for the specific bands assigned to
      the Hcmbpy ligand. This collapse demonstrates that the Ru complexes bind DNA
      through the Hcmbpy moiety, and intercalation is suggested as the binding mode.
      The DNA binding by the enantiopure Ru complexes (Delta or Lambda) is more
      efficient than by the racemic complexes.

PMID- 16421856
TI  - Construction and evaluation of a kinetic scheme for RecA-mediated DNA strand
      exchange.
AB  - The Escherichia coli RecA protein is the prototype of a class of proteins playing
      a central role in genomic repair and recombination in all organisms. The
      unresolved mechanistic strategy by which RecA aligns a single strand of DNA with
      a duplex DNA and mediates a DNA strand switch is central to understanding its
      recombinational activities. Toward a molecular-level understanding of RecA
      mediated DNA strand exchange, we explored its mechanism using oligonucleotide
      substrates and the intrinsic fluorescence of 6-methylisoxanthopterin (6MI).
      Steady- and presteady-state spectrofluorometric data demonstrate that the
      reaction proceeds via a sequential four-step mechanism comprising a rapid,
      bimolecular association step followed by three slower unimolecular steps.
      Previous authors have proposed multistep mechanisms involving two or three steps.
      Careful analysis of the differences among the experimental systems revealed a
      previously undiscovered intermediate (N1) whose formation may be crucial in the
      kinetic discrimination of homologous and heterologous sequences. This observation
      has important implications for probing the fastest events in DNA strand exchange
      using 6MI to further elucidate the molecular mechanisms of recombination and
      recombinational repair.

PMID- 16421857
TI  - Characterization of bacterial growth and the influence of antibiotics by means of
      UV resonance Raman spectroscopy.
AB  - In this work we monitor the bacterial growth of a Bacillus pumilus batch culture
      by means of UV resonance Raman spectroscopy. Excitation with a wavelength of 244
      nm especially enhances the Raman scattering of the aromatic amino acids and the
      nucleic acid bases and therefore is a good method to track the metabolic changes
      that occur during bacterial growth. Furthermore, a drug from the fluoroquinolone
      group is added to the bacterial suspension at the beginning of the exponential
      growth phase. With the help of chemometrical methods such as hierarchical cluster
      analysis (HCA) and principal component analysis (PCA) it is possible to visualize
      the small changes that occur in the UV resonance Raman spectra due to the
      interaction of the drug with its biological targets DNA and the enzyme gyrase
      within the bacterial cell.

PMID- 16421858
TI  - Classification of lactic acid bacteria with UV-resonance Raman spectroscopy.
AB  - UV-resonance Raman spectroscopy is applied as a method for the identification of
      lactic acid bacteria from yogurt. Eight different strains of bacteria from
      Lactobacillus acidophilus, L. delbrueckii ssp. bulgaricus, and Streptococcus
      thermophilus were investigated. At an excitation wavelength of 244 nm signals
      from nucleic acids and proteins are selectively enhanced. Classification was
      accomplished using different chemometric methods. In a first attempt, the
      unsupervised methods hierarchical cluster analysis and principal component
      analysis were applied to investigate natural grouping in the data. In a second
      step the spectra were analyzed using several supervised methods: K-nearest
      neighbor classifier, nearest mean classifier, linear discriminant analysis, and
      support vector machines.

PMID- 16421859
TI  - An enhanced LC-MS/MS method for microcystin-LR in lake water.
AB  - A LC-MS/MS method with enhanced sensitivity and specificity was established for
      monitoring microcystin-LR (MC-LR) in drinking water supplies in southern Taiwan.
      The enhanced sensitivity was achieved by the selection of a doubly charged MC-LR
      as the precursor ion to result in an multiple reaction monitoring (MRM) pair ions
      of m/z 498.6 --> 135.0. Using this ion pair, a record low detection limit of 2 pg
      was achieved on column, found in the available literature. A sample preparation
      method involving C8 solid-phase extraction gave satisfactory recoveries of the
      analyte. Nodularin, with structural similarity to MC-LR, was used as an internal
      standard to minimize matrix effects of water samples collected from six different
      water reservoirs in southern Taiwan, where MC-LR was detected at sub-ppb levels
      in all the reservoirs. The best precision and accuracy of this method were found
      with samples prepared to contain MC-LR at 0.1 and 1 microg l(-1). This new method
      requires considerably smaller water sample volumes because of enhanced
      quantification sensitivity and hence reduces the time needed for analysis. It
      should serve as a useful example for method development for monitoring other
      members of the microcystin family in drinking water supplies.

PMID- 16421860
TI  - Characterization of host-guest complexes of cucurbit[n]uril (n = 6, 7) by
      electrospray ionization mass spectrometry.
AB  - When an intramolecular cavity exists in a molecule, it can trap another chemical
      species to form a host-guest complex. We examine the formation of such an
      inclusion complex with cucurbit[n]uril (CBn, n = 6, 7) as the host to trap alkali
      metal or ammonium ions as the guest, by electrospray ionization mass spectrometry
      (ESI-MS). The results show that the inclusion complexes are formed between the
      three-dimensional cylinder of CBn hosts and the guest cations. Selectivity of the
      complex formation is dependent both on (1) ion-dipole interactions between the
      cylindrical portal of the CBn hosts and the guest cations and (2) the hydrophobic
      interactions at the inner cavity of CBn.

PMID- 16421861
TI  - Reactions of a modified lysine with aldehydic and diketonic dicarbonyl compounds:
      an electrospray mass spectrometry structure/activity study.
AB  - The phenomenon known as non-enzymatic glycation is described as the reaction of
      reducing sugars with basic amino groups of proteins and nucleic acids, as well as
      with simple amines, without enzyme mediation. Non-enzymatic model glycation
      reactions that make use of low-molecular-weight compounds make an important
      contribution in the elucidation of glicated processes in vitro and in vivo. Four
      alpha-dicarbonyl compounds, aldehydic (glyoxal, methylglyoxal and phenylglyoxal)
      and ketonic (diacetyl), were reacted with the modified amino acid N(alpha)-acetyl
      L-lysine (AcLys) in an attempt to establish structure/activity relationships for
      the reactivity of alpha-dicarbonyls with the amine compound. Electrospray
      ionization mass spectrometry (ESI-MS) combined with tandem mass spectrometry
      (MS/MS) and collision-induced dissociation (CID) was used to identify and
      characterize reagents, intermediates and reaction products. The formation of
      dicarbonyl-derived lysine dimers was observed exclusively. Especially, attention
      is drawn to alkyl- (asymmetrical dicarbonyl systems) and carboxyl- (glyoxal
      system) substituted imidazolium ions, at ring position 2. The main differences
      observed in the reactions studied were related to the reactivity with the diimine
      intermediate. This intermediate can react either with a non-hydrated dicarbonyl
      molecule at the aldehydic carbonyl, or with a mono-hydrated one at the ketonic
      carbonyl, particularly for asymmetrical dicarbonyls. For 2-carboxyl-substituted
      imidazolium ion (glyoxal reaction), besides the usual keto-enol rearrangement
      from the diol group, an alternative reaction pathway (proton abstraction) appears
      to contribute also for the imidazolium ring-closure process. Moreover, the
      formation of imidazolium ring structures can depend on several factors, namely,
      the presence (or absence) of electron donor substituents at the formed diol, the
      degree of stability of the new electrophile generated and/or the equilibrium
      concentration of the non- and mono-hydrated dicarbonyl forms in solution, the
      last being particularly important for asymmetrical dicarbonyls. The results
      reported reveal the complexity of reactivity as well as the diversity of
      imidazolium molecular structures.

PMID- 16421862
TI  - Is there a link between adult neurogenesis and learning?
AB  - During the past several years, evidence has accumulated suggesting a relationship
      between newly born cells in the hippocampus and various types of learning and
      memory. However, most of the evidence is correlational and some of it does not
      agree. This review discusses both sides of this issue, considering the effects of
      learning on the production of new neurons in the dentate gyrus and the question
      of whether newly born cells participate in learning and memory.

PMID- 16421863
TI  - Alcohol and adult neurogenesis: roles in neurodegeneration and recovery in
      chronic alcoholism.
AB  - The concept of "structural plasticity" has emerged as a potential mechanism in
      neurodegenerative and psychiatric diseases such as drug abuse, depression, and
      dementia. Chronic alcoholism is a progressive neurodegenerative disease while the
      person continues to abuse alcohol, though clinical and imaging studies show that
      some recovery may occur with abstinence. The neural plasticity observed in
      chronic alcoholism coupled with conflicting reports on alcohol-induced
      hippocampal neuropathology make this disease ripe for reconsideration in terms of
      the phenomenon of adult neurogenesis. This review describes opposing neurogenic
      processes that occur with alcohol intoxication and abstinence following alcohol
      dependence and how these opposing events relate to neurodegeneration and recovery
      from chronic alcoholism.

PMID- 16421864
TI  - Estimation of survival functions in interval and right censored data using STD
      behavioural diaries.
AB  - In investigations of sexually transmitted diseases (STDs), true infection times
      are often either interval censored or right censored. For such data, reliable
      estimation of the survival function is difficult to obtain. In this research, we
      propose a resampling based method for the estimation of the survival function
      using auxiliary behavioural information provided by daily diaries. By imputing
      the unknown infection time from a list of sexual encounter times recorded in the
      diaries, the proposed procedure can be easily implemented using existing
      estimation procedures for right censored data. Our simulations show that the
      proposed procedure consistently outperforms the existing ad hoc estimation
      methods and produces smaller mean integrated squared errors (MISE). We illustrate
      this method by analysing infection data obtained from an ongoing STD
      investigation of adolescent females.

PMID- 16421865
TI  - Fragmentation and skeletal rearrangements of 2-arylylamino-5-aryl-1,3,4
      oxadiazoles and their noncovalent complexes with cobalt cation and cyclodextrin
      studied by mass spectrometry.
AB  - Mass spectrometric fragmentation pathways of title compounds were studied by
      electron ionization (EI) and electrospray ionization (ESI) as methods of ion
      generation. To explain the observed complex skeletal rearrangements, tandem mass
      spectrometry, accurate mass measurement and isotope labeling (compounds
      containing one 13C atom in oxadiazole ring) were used. Loss of CO, N2 and H atoms
      under EI conditions led to the formation of 9,10-dihydroacridine-type ions, loss
      of NH3 under ESI conditions yielded the 4-phenylphthalazinone-type ions and the
      loss of HNCO under ESI conditions produced N-arylamino-benzonitrilium ions;
      however, this process can be affected by the electron-donor/electron-withdrawing
      properties of groups substituted at the phenyl rings. The ESI was used to study
      the complexes of the compounds with cobalt as well as with cyclodextrin. It was
      found that the compounds studied tend to form inclusion complexes with
      cyclodextrin of stoichiometry 1:1 and complexes of different stoichiometries with
      cobalt, although those of stoichiometry 6:1 and 4:1 are favored and the
      attachment of counter ion may stabilize the complexes 3:1 and 2:1.

PMID- 16421866
TI  - The fate of glyoxal and methylglyoxal in peritoneal dialysis.

PMID- 16421867
TI  - Falsely elevated C4-carnitine as expression of glutamate formiminotransferase
      deficiency in tandem mass spectrometry newborn screening.

PMID- 16421868
TI  - Preparative separation of a multicomponent peptide mixture by mass spectrometry.
AB  - We report on the first multiplex preparative separation by mass spectrometry of
      bio-organic molecules in the 200-350 Da mass range that is typical for synthetic
      drugs. A five-component mixture consisting of two di- and three tripeptides has
      been separated by mass using a specially designed mass spectrometer. The
      instrument for preparative separations consists of an electrospray ionization
      (ESI) source, ion transfer optics, an electrostatic sector, and an inhomogeneous
      field magnetic mass analyzer that achieves linear mass dispersion of ion beams.
      Protonated peptides produced by electrospray were separated, nondestructively
      landed on a 16-channel array of dry collector plates, and reconstituted in
      solution. The preparation procedures and the instrumental conditions have been
      optimized to maximize the ion currents. The significant features of the special
      mass spectrometer are high ion currents and simultaneous separation and
      collection of mixture components.

PMID- 16421869
TI  - Variability in conduction of the lateral femoral cutaneous nerve.
AB  - The purpose of this study was to establish a reliable technique for assessing
      conduction in the lateral femoral cutaneous nerve (LFCN), bearing in mind its
      anatomical variation. Based on our anatomical study, normative values were
      obtained in 40 healthy nerves. The optimal stimulation site was located 1 cm or
      more media 16470526 l to the anterior superior iliac spine (ASIS) in 93% of cases
      and over the ASIS in 7%. Sensory nerve action potentials (SNAPs) were recorded
      simultaneously along an imaginary line between the ASIS and the lateral border of
      the patella and 2 cm medial to this line. Side-to-side variability in amplitude
      was 31% for the recording from the line and 30% for the medial recording. The
      variability significantly decreased to 16% when the higher value of each side was
      compared. Therefore, the measurement of higher amplitude recorded at two
      different sites may minimize interside variability and improve the diagnostic
      utility of the LFCN conduction study.

PMID- 16421870
TI  - Automated software-guided identification of new buspirone metabolites using
      capillary LC coupled to ion trap and TOF mass spectrometry.
AB  - The identification and structure elucidation of drug metabolites is one of the
      main objectives in in vitro ADME studies. Typical modern methodologies involve
      incubation of the drug with subcellular fractions to simulate metabolism followed
      by LC-MS/MS or LC-MS(n) analysis and chemometric approaches for the extraction of
      the metabolites. The objective of this work was the software-guided
      identification and structure elucidation of major and minor buspirone metabolites
      using capillary LC as a separation technique and ion trap MS(n) as well as
      electrospray ionization orthogonal acceleration time-of-flight (ESI oaTOF) mass
      spectrometry as detection techniques. Buspirone mainly underwent hydroxylation,
      dihydroxylation and N-oxidation in S9 fractions in the presence of phase I co
      factors and the corresponding glucuronides were detected in the presence of phase
      II co-factors. The use of automated ion trap MS/MS data-dependent acquisition
      combined with a chemometric tool allowed the detection of five small
      chromatographic peaks of unexpected metabolites that co-eluted with the larger
      chromatographic peaks of expected metabolites. Using automatic assignment of ion
      trap MS/MS fragments as well as accurate mass measurements from an ESI oaTOF mass
      spectrometer, possible structures were postulated for these metabolites that were
      previously not reported in the literature.

PMID- 16421871
TI  - Enantiomeric excess determination of a chiral carboxylic acid using the
      enantiomer-labeled host method by electrospray ionization mass spectrometry.

PMID- 16421873
TI  - Mass spectrometric characterization of lipid-modified peptides for the analysis
      of acylated proteins.
AB  - The analysis of acylated proteins by mass spectrometry (MS) has largely been
      overshadowed in proteomics by the analysis of glycosylated and phosphorylated
      proteins; however, lipid modifications on proteins are proving to be of
      increasing importance in biomedical research. In order to identify the marker
      ions and/or neutral loss fragments that are produced upon collision-induced
      dissociation, providing a means to identify the common lipid modifications on
      proteins, peptides containing an N-terminally myristoylated glycine, a
      palmitoylated cysteine and a farnesylated cysteine were chemically synthesized.
      Matrix-assisted laser desorption/ionization time-of-flight time-of-flight (MALDI
      TOF-TOF), electrospray ionization quadrupole time-of-flight (ESI Q-TOF), and
      electrospray ionization hybrid triple-quadrupole/linear ion trap (ESI QqQ(LIT))
      mass spectrometers were used for the analysis. The peptide containing the N
      terminally myristoylated glycine, upon CID, produced the characteristic fragments
      a1 (240.4 Th) and b1 (268.4 Th) ions as well as a low-intensity neutral loss of
      210 Da (C14H26O). The peptides containing a farnesylated cysteine residue
      fragmented to produce a marker ion at a m/z of 205 Th (C15H25) as well as other
      intense farnesyl fragment ions, and a neutral loss of 204 Da (C15H24). The
      peptides containing a palmitoylated cysteine moiety generated neutral losses of
      238 Da (C16H30O) and 272 Da (C16H32OS); however, no marker ions were produced.
      The neutral losses were more prominent in the MALDI-TOF-TOF spectra, whereas the
      marker ions were more abundant in the ESI QqQ(LIT) and Q-TOF mass spectra.

PMID- 16421872
TI  - Deuterium isotope effects observed during competitive binding chiral recognition
      electrospray ionization--mass spectrometry of cinchona alkaloid-based systems.
AB  - Deuterium isotope effects are reported for binding between tert-butylcarbamoyl
      quinine/quinidine chiral selectors and isotopomeric quasienantiomers of N-(3,5
      dinitrobenzoyl)leucine measured using electrospray ionization-mass spectrometry
      (ESI-MS) and competitive binding. Evaluation of mixtures of each selector with
      one labeled and one unlabeled enantiomeric selectand of identical configuration
      showed a significant difference in measured ion abundances of diastereomeric
      complexes between the selector and each selectand. It was found that in some
      cases, the complex containing the nondeuterated selectand was 15% more abundant
      than its deuterated counterpart. On the basis of an assessment of solution- and
      gas-phase isotope effects reported in the literature, a series of control
      experiments were performed to study the origin of the effects. On the basis of
      these measurements, our preliminary conclusion is that the differing gas-phase
      physicochemical nature of the deuterated versus nondeuterated selectand
      represents the strongest contribution to the observed effect in this chiral
      molecular recognition system.

PMID- 16421874
TI  - Collision-induced dissociation studies of protonated ether--(H2O)n (n = 1-3)
      clusters.
AB  - We have studied the protonated ether-(H2O)n (n = 1-3) complexes containing
      tetrahydrofuran, dimethyl, diethyl, dibutyl, and butylmethyl ethers using a
      flowing afterglow triple-quadrupole mass spectrometer. Collision-induced
      dissociation, CID, of all clusters with n = 1, 2 shows sequential water loss. The
      n = 3 cluster of dimethyl ether shows sequential water loss, while all other
      ether clusters display selective product formation. The CID spectra are
      interpreted based on known energetics, and theoretical studies of the dimethyl
      and diethyl ether systems.

PMID- 16421875
TI  - The detection of red pigment-concentrating hormone (RPCH) in crustacean eyestalk
      tissues using matrix-assisted laser desorption/ionization-Fourier transform mass
      spectrometry: [M + Na]+ ion formation in dried droplet tissue preparations.
AB  - Red pigment-concentrating hormone (RPCH), an octapeptide found in crustaceans and
      insects with the sequence pGlu-Leu-Asn-Phe-Ser-Pro-Gly-Trp-NH2, is an N- and C
      terminally blocked uncharged peptide. These structural features are shared with
      many members of the larger adipokinetic hormone (AKH)/RPCH peptide family in
      insects. We have applied vacuum UV matrix-assisted laser desorption/ionization
      (MALDI)-Fourier transform ion cyclotron mass spectrometry (FTMS) to the direct
      analysis of crustacean sinus gland tissues, using 2,5-dihydroxybenzoic acid (DHB)
      as the MALDI matrix, and have found that RPCH is detected in the cationized, [M +
      Na]+, form under conditions where other peptides in the direct tissue spectra are
      protonated without accompanying [M + Na]+ or [M + K]+ satellite peaks. The [M +
      H]+ ion for RPCH is not detected in tissue samples or for an RPCH standard, even
      when care is taken to eliminate metal ions. This behavior is not unprecedented;
      however, both direct tissue spectra and SORI-CID spectra provide no clues to
      suggest that the ionizing agent is a metal cation. In this communication, we
      characterize the MALDI-FTMS ionization and SORI-CID mass spectra of the [M + Na]+
      and [M + K]+ ions from RPCH, and report on the detection of this neuropeptide in
      sinus gland tissues from the lobster Homarus americanus and the kelp crab
      Pugettia producta. We describe two strategies, an on-probe extraction procedure
      and a salt-doping approach, that can be applied to previously analyzed MALDI
      tissue samples to enhance and unmask sodiated peptides that may otherwise be
      mistaken for novel neuropeptides.

PMID- 16421876
TI  - Mass spectrometric characterization of efaproxiral (RSR13) and its implementation
      into doping controls using liquid chromatography-atmospheric pressure ionization
      tandem mass spectrometry.
AB  - Efaproxiral (2-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxyl]-2
      methylpropionic acid, formerly referred to as RSR13) is prohibited in sports
      according to the World Anti-Doping Agency (WADA). The drug as well as
      structurally related compounds and a stable isotope-labeled derivative have been
      synthesized to elucidate the fragmentation pathway of efaproxiral, using
      electrospray ionization (ESI) and tandem mass spectrometry by employing a novel
      linear ion trap--orbitrap hybrid mass spectrometer--in positive and negative
      ionization modes. The elimination of 2-methyl acrylic acid (-86 u) has been
      identified as a major fragmentation process in both charge states. Negative
      ionization and collision-induced dissociation (CID) caused an additional release
      of carbon dioxide (-44 u), and positive ionization the loss of formic acid (-46
      u). Efaproxiral was incorporated into an existing screening procedure for doping
      controls using solid-phase extraction (SPE) followed by liquid chromatography
      tandem mass spectrometry, enabling a limit of detection of 2.5 ng/ml and interday
      precisions ranging from 7.9 to 13.0%.

PMID- 16421877
TI  - Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality
      and toxicity of sulfur mustard administered through percutaneous route.
AB  - Sulfur mustard (SM), chemically bis (2-chloroethyl) sulfide is a bifunctional
      alkylating agent that causes serious blisters on contact with human skin.
      Although several antidotes have been reported for the systemic toxicity of SM in
      experimental animals none of them are approved so far and decontamination of SM
      immediately by physical or chemical means is recommended as the best protection.
      Two compounds amifostine [S-2(3-aminopropylamino) ethyl phosphorothioate] and
      DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulfide] gave very good protection
      as an oral prophylactic agent against SM the in mouse model, but in the rat model
      the protection was only moderate. In the search for more effective and less toxic
      compounds, a number of analogues of DRDE-07 were synthesised and their protective
      efficacy was evaluated in mouse and rat models. The LD50 of S-aryl substitution
      was between 1 and 2 g kg(-1) and S-alkyl substitution was more than 2 g kg(-1).
      In the mouse model, DRDE-07, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 gave about 20
      fold protection, and DRDE-23 and DRDE-38 gave less protection of 4.8 and 9.0 fold
      respectively, against percutaneously administered SM. In the rat model, DRDE-07,
      DRDE-09, DRDE-10 and DRDE-21 gave about two fold protection. Percutaneously
      administered SM (19.33 mg kg(-1)) significantly depleted the hepatic GSH content
      in mice. Pretreatment with DRDE-21 significantly elevated the levels. A 4.4 fold
      increase in % DNA fragmentation was observed 7 days after SM administration
      (19.33 mg kg(-1)) in mice. Pretreatment with DRDE-07, DRDE-09, DRDE-10, DRDE-21,
      DRDE-30 and DRDE-35 significantly protected the mice from SM induced DNA damage.
      The histopathological lesions in liver and spleen induced by percutaneously
      administered SM was reduced by pretreatment with DRDE-07, DRDE-09, DRDE-10 and
      DRDE-21. These analogues may prove as prototypes for the designing of more
      effective prophylactic drug for SM.

PMID- 16421878
TI  - Study of phytochelatins and other related thiols as complexing biomolecules of As
      and Cd in wild type and genetically modified Brassica juncea plants.
AB  - The accumulation of As and Cd in Brassica juncea plants and the formation of
      complexes of these elements with bioligands such as glutathione and/or
      phytochelatins (PCs) is studied. The genetic manipulation of these plants to
      induce higher As and Cd accumulation has been achieved by overexpressing the
      genes encoding for gamma-glutamyl cysteine synthetase (gamma-ECS) and glutathione
      synthetase (GS). These two enzymes are responsible for glutathione (GSH)
      formation in plants, which is the first step in the production of PCs. The
      biomass produced in both the wild type and the genetically modified plants, has
      been evaluated. Additionally, the total Cd and As concentration accumulated in
      the plant tissues was measured by inductively coupled plasma mass spectrometry
      (ICP-MS) after extraction. Speciation studies on the extracts were conducted
      using size exclusion liquid chromatography (SEC) coupled online with ICP-MS to
      monitor As, Cd and S. For further purification of the As fractions, reversed
      phase high performance liquid chromatography (RP-HPLC) was used. Structural
      elucidation of the PCs and other thiols, as well as their complexes with As and
      Cd, was performed by electrospray-quadrupole-time-of-flight (ESI-Q-TOF). In both
      the Cd and As exposed plants it was possible to observe the presence of oxidized
      PC2 ([M + H]+, m/z 538), GS-PC2(-Glu) ([M + H]+, m/z 716) as well as reduced GSH
      ([M + H]+, m/z 308) and oxidized glutathione (GSSG) ([M + H]+, m/z 613). However,
      only the GS plants exhibited the presence of As(GS)3 complex ([M + H]+, m/z 994)
      that was further confirmed by MS/MS. This species is reported for the first time
      in B. juncea plant tissues.

PMID- 16421880
TI  - Depression of involuntary activity in muscles paralyzed by spinal cord injury.
AB  - Involuntary muscle contractions are common after spinal cord injury (SCI).
      Increased sensitivity to Ia muscle afferent input may contribute to the
      development of these spasms. Since tendon vibration results in a period of
      postactivation depression of the Ia synapse, we sought to determine whether
      Achilles tendon vibration (80 HZ for 2 s) altered involuntary contractions evoked
      by superficial peroneal nerve (SPN) stimulation (5 pulses at 300 HZ) in paralyzed
      leg muscles of subjects with chronic (>1 year) SCI. Responses to SPN stimulation
      that were conditioned by vibration were reduced in 66% of trials (by 33+/-12% in
      tibialis anterior and 40+/-16% in soleus). These reductions in electromyographic
      activity are unlikely to be mediated by changes at the Ia synapse or motoneuron
      because vibration did not alter the magnitude of the soleus H reflex. The
      electromyographic reductions may involve long-lasting neuromodulatory effects on
      spinal inhibitory interneurons or synapses involved in the flexor reflex pathway.
      Vibration-evoked depression of electromyographic activity may be clinically
      useful in controlling involuntary muscle contractions after SCI.

PMID- 16421881
TI  - Targeted suppression of an amyloidogenic transthyretin with antisense
      oligonucleotides.
AB  - Transthyretin (TTR) amyloidosis, the most common form of hereditary systemic
      amyloidosis, is characterized clinically by adult-onset axonal neuropathy and
      restrictive cardiomyopathy. More than 85 mutations in transthyretin have been
      found to cause this hereditary disease. Since essentially all circulating TTR is
      of hepatic origin, orthotopic liver transplantation has been used as the only
      specific form of therapy. Unfortunately, in many patients amyloid deposition
      continues after orthotopic liver transplantation, indicating that mutant TTR is
      no longer required for progression of the disease after tissue deposits have been
      initiated. As a first step toward medical treatment of this disease, we have
      employed antisense oligonucleotides (ASOs) to inhibit hepatic expression of TTR.
      A transgenic mouse model carrying the human TTR Ile84Ser mutation was created and
      shown to express high levels of human mutant transthyretin. TTR ASOs suppressed
      hepatic TTR mRNA levels and serum TTR levels by as much as 80%. Suppression of
      hepatic synthesis of transthyretin may offer a medical treatment for
      transthyretin systemic amyloidosis.

PMID- 16421882
TI  - Response of the dropped head/bent spine syndrome to treatment with intravenous
      immunoglobulin.
AB  - Weakness of neck extension causing a dropped head may result from many
      neuromuscular disorders. One etiology is isolated neck extensor myopathy. A
      similar focal myopathy of the lower axial muscles may cause the bent spine
      syndrome, which manifests as flexion of the trunk and inability to stand upright.
      Combination of both dropped head and bent spine myopathies is uncommon.
      Inflammation is usually not pronounced in these conditions and response to
      immunosuppressive treatment is rare. We present an 81-year-old man who developed
      progressive weakness of neck and trunk extension over several months, with a
      prominent inflammatory process in the thoracic paraspinal muscles, which
      responded dramatically to treatment with intravenous immunoglobulin (IVIg). This
      case, together with other rare reports, suggests that the presence of
      inflammation in the biopsy of an affected muscle may predict treatment response.

PMID- 16421883
TI  - Meralgia paresthetica: clinical and electrophysiological diagnosis in 120 cases.
AB  - We report the results of clinical and electrophysiological examinations in 131
      cases of meralgia paresthetica (MP) among 120 unselected patients, 69 men and 51
      women, aged 15-81 years. All patients experienced permanent or intermittent pain,
      and all but one had permanent sensory impairment of the thigh. The lateral aspect
      of the thigh was solely involved in 88 cases and the anterior aspect was also or
      exclusively involved in 32 cases. The right thigh was involved 62 times and the
      left 58 times. Symptom duration varied from 2 weeks to 20 years. The initial
      diagnosis was meralgia paresthetica in 47 cases (39%), root disease in 35 cases,
      and osteoarthritis in 6 cases; no diagnosis was proposed in the 32 remaining
      cases. Two cases had undergone previous spine surgery for disk herniation, with
      no benefit. A precise cause could explain the lateral femoral cutaneous nerve
      (LFCN) lesion in 46 cases, the other 74 cases being considered idiopathic (25% of
      patients were obese). Only one case required surgery to relieve symptoms. LFCN
      conduction was studied orthodromically, distally from the anterior superior iliac
      spine. The side-to-side amplitude ratio (ssRatio) was greater than 2.3 in 118 of
      120 patients (98.3%) and was a better index to confirm a lesion of the LFCN than
      SNAP amplitude, which was abnormal (less than 3 microV) in 88 cases (73.3%). Only
      two of the 11 bilateral cases had an ssRatio lower than 2.3 (they were both 2.0).
      An ssRatio of 2.3 or more and a SNAP amplitude lower than 3 microV provided a
      specificity of 98.75% or more. The mean axonal loss was 88%. These clinical and
      electrophysiological data highlight the central role the neurophysiologist should
      play in diagnosing MP by means of an LFCN conduction study.

PMID- 16421884
TI  - Sensitivity of repetitive facial-nerve stimulation in patients with myasthenia
      gravis.
AB  - Repetitive stimulation of the facial nerve is commonly performed in cases of
      suspected myasthenia gravis (MG) because bulbar weakness is often present, but
      the most sensitive facial muscle is unknown. We compared the sensitivity of
      repetitive nerve stimulation (RNS) to the frontalis and nasalis muscles in 244
      patients with suspected MG. We found no difference in sensitivity of RNS when
      recording from these muscles in both ocular and generalized MG. In addition, we
      confirmed the low sensitivity of RNS for ocular (18%) or generalized (47%) MG.
      The specificity of facial RNS for both muscles was 100% and, in certain
      circumstances, may obviate the need for further diagnostic testing.

PMID- 16421885
TI  - Sensorineural hearing loss in combined modality treatment of nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Combined modality therapy has become the standard of care for
      nasopharyngeal carcinoma, yet the combined ototoxic effects of radiation and
      cisplatin are poorly understood. The incidence and severity of sensorineural
      hearing loss (SNHL) with combined modality therapy was evaluated and the dose
      response relation between radiation and hearing loss was investigated. METHODS:
      Patients with newly diagnosed AJCC Stage II-IVB nasopharynx carcinoma treated
      from 1994-2003 were identified. The records of 44 ears in 22 patients who
      received a preirradiation pure tone audiogram and followup audiograms 12+ months
      postirradiation were included in the analysis. All patients were treated with
      conformal radiotherapy to 70 Gy and received platinum-based chemotherapy similar
      to the Intergroup 0099 trial. Composite cochlear dose distributions were
      calculated. Ototoxicity was measured using intrasubject audiogram comparisons and
      SNHL was defined as per the American Speech and Hearing Association guidelines,
      with standard range of speech between 2000-4000 Hz. SNHL was analyzed using
      Fisher exact test and linear and logistic regression models. RESULTS:  PATIENT
      CHARACTERISTICS: median age, 45; 27% Asian; 68% male; 64% WHO III. Median
      audiologic followup was 29 months (range, 12-76 mos). Mean cochlear dose (Dmean)
      ranged from 28.4-70.0 Gy (median, 48.5 Gy). SNHL was detected in 25 of the 44
      ears (57%) studied. There was an increased risk of SNHL for ears receiving Dmean
      > 48 Gy compared with those receiving < or = 48 Gy at all frequencies within the
      range of speech (P = 0.04). Using univariate logistic regression analysis, Dmean
      to the cochlea, cycles of cisplatin, and time postradiotherapy were independently
      significant factors in determining the incidence of SNHL (P = 0.02, P = 0.03, and
      P = 0.04, respectively). In univariate and multivariate linear regression
      analysis, Dmean was statistically significant at all frequencies in affecting
      degree of SNHL, whereas the significance of cisplatin and time was variable.
      CONCLUSIONS: There was a significant increase in risk of SNHL among patients
      receiving > 48 Gy, suggesting a threshold in cochlear radiation dose-response in
      the setting of combined modality therapy. This dose should serve as a Dmean
      constraint maximum for intensity-modulated radiotherapy treatment of nasopharynx
      carcinoma.

PMID- 16421887
TI  - Are all melanomas the same? Spitzoid melanoma is a distinct subtype of melanoma.
AB  - BACKGROUND: Although the majority of melanomas demonstrate high rates of
      mutations in B-RAF or N-RAS that result in constitutive activation of the mitogen
      activated protein kinase-signaling pathway, emerging data suggest molecular
      differences among melanoma subtypes. In this study, the authors evaluated the
      contribution of B-RAF and N-RAS mutations to the pathogenesis of Spitzoid
      melanomas. METHODS: In total, 33 Spitzoid melanomas were analyzed for clinical
      and pathologic characteristics as well as for hot-spot mutations in the B-RAF and
      N-RAS genes. In the majority of patients (28 of 33 melanomas), the tumors were
      confined to the skin with no evidence of metastasis (average follow-up, 32.5
      mos). There were five metastasizing melanomas (5 of 33 tumors) with regional or
      systemic spread. RESULTS: Of 33 Spitzoid melanomas, only 1 showed the V600E
      mutation in the B-RAF gene (1 of 33 tumors; 3%). It was noteworthy that none of
      the metastatic Spitzoid melanomas (0 of 5 tumors; 0%), of which 2 resulted in
      fatal outcomes, demonstrated mutations in B-RAF or N-RAS. CONCLUSIONS: In
      contrast to the majority of cutaneous melanomas, activating hot-spot mutations in
      B-RAF or N-RAS were not involved in the pathogenesis of Spitzoid melanoma. These
      data suggested that Spitzoid melanoma is a distinct form of melanoma with unknown
      genes and/or signaling pathways involved in its development.

PMID- 16421889
TI  - Selective mutism: more than social anxiety?
AB  - This study investigated the relationship between selective mutism (SM), social
      phobia (SP), oppositionality, and parenting styles. Twenty-one children with SP,
      21 children with SM and SP, and 21 normal children ages 7-15, and the mother of
      each child, participated in an assessment of psychopathological factors
      potentially related to SM. Children with SM did not endorse higher levels of
      social anxiety than did children with SP, although clinicians gave higher
      severity ratings to those who had both disorders. In addition, although a
      dimensional measure of oppositionality (Eyberg Child Behavior Inventory) did not
      reveal group differences, there were significantly more diagnoses of oppositional
      defiant disorder among children with SM (29%) in comparison to children with SP
      alone (5%). With respect to parenting styles, there were no significant
      differences among parents of children with SM and the other groups, except that
      children with SP reported significantly less warmth/acceptance from parents than
      normal children. These data replicate previous findings that children with SM do
      not report greater social anxiety than other children with a SP diagnosis.
      Furthermore, they suggest that oppositional behaviors may be part of the clinical
      presentation of a subset of children with SM.

PMID- 16421886
TI  - A developmental fMRI study of self-regulatory control.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the neural
      correlates of self-regulatory control across development in healthy individuals
      performing the Stroop interference task. Proper performance of the task requires
      the engagement of self-regulatory control to inhibit an automatized response
      (reading) in favor of another, less automatic response (color naming). Functional
      MRI scans were acquired from a sample of 70 healthy individuals ranging in age
      from 7 to 57 years. We measured task-related regional signal changes across the
      entire cerebrum and conducted correlation analyses to assess the associations of
      signal activation with age and with behavioral performance. The magnitude of fMRI
      signal change increased with age in the right inferolateral prefrontal cortex
      (Brodmann area [BA] 44/45) and right lenticular nucleus. Greater activation of
      the right inferolateral prefrontal cortex also accompanied better performance.
      Activity in the right frontostriatal systems increased with age and with better
      response inhibition, consistent with the known functions of frontostriatal
      circuits in self-regulatory control. Age-related deactivations in the mesial
      prefrontal cortex (BA 10), subgenual anterior cingulate cortex (BA 24), and
      posterior cingulate cortex (BA 31) likely represented the greater engagement of
      adults in self-monitoring and free associative thought processes during the
      easier baseline task, consistent with the improved performance on this task in
      adults compared with children. Although we cannot exclude the possibility that
      age-related changes in reading ability or in the strategies used to optimize task
      performance were responsible for our findings, the correlations of brain
      activation with performance suggest that changes in frontostriatal activity with
      age underlie the improvement in self-regulatory control that characterizes normal
      human development.

PMID- 16421890
TI  - Comparative postnatal ontogeny of the skull in the australidelphian metatherian
      Dasyurus albopunctatus (Marsupialia: Dasyuromorpha: Dasyuridae).
AB  - We describe the cranial ontogeny of an australidelphian marsupial, Dasyurus
      albopunctatus, using a combination of qualitative and quantitative approaches. We
      examined in detail qualitative morphological changes of just-weaned individuals
      as compared to old adults; specifically, changes in 31 morphological structures
      (e.g., processes, foramina) and 38 changes in cranial joints. We also interpreted
      growth-invariant structures in terms of their functional relevance. We performed
      a multivariate allometry analysis based on 14 cranial measurements taken from 31
      specimens encompassing the entire postweaning period. Three variables (height of
      occipital plate, breadth of braincase, and height of mandible) showed the same
      allometric trends in D. albopunctatus and the three marsupial species studied
      previously in the same framework (Didelphis albiventris, Lutreolina
      crassicaudata, and Dromiciops gliroides). In addition, D. albopunctatus shared
      allometric trends in two variables (length of the upper postcanine row and length
      of the orbit) with the microbiotheriid D. gliroides. Most of the growth trends
      observed are interpreted as linked to the predominantly carnivorous dietary habit
      of adult D. albopunctatus. Because dasyuromorphians are most likely basal to the
      major Australasian radiation of marsupials, knowledge of ontogenetic changes in
      D. albopunctatus may shed light on the evolution of ontogeny in the highly
      diverse Australasian marsupial fauna.

PMID- 16421891
TI  - Evolution and homology of the astragalus in early amniotes: new fossils, new
      perspectives.
AB  - The reorganization of the ankle in basal amniotes has long been considered a key
      innovation allowing the evolution of more terrestrial and cursorial behavior.
      Understanding how this key innovation arose is a complex problem that largely
      concerns the homologizing of the amniote astragalus with the various
      ossifications in the anamniote tarsus. Over the last century, several hypotheses
      have been advanced homologizing the amniote astragalus with the many
      ossifications in the ankle of amphibian-grade tetrapods. There is an emerging
      consensus that the amniote astragalus is a complex structure emerging via the co
      ossification of several originally separate elements, but the identities of these
      elements remain unclear. Here we present new fossil evidence bearing on this
      contentious question. A poorly ossified, juvenile astragalus of the large
      captorhinid Moradisaurus grandis shows clear evidence of four ossification
      centers, rather than of three centers or one center as posited in previous models
      of astragalus homology. Comparative material of the captorhinid Captorhinikos
      chozaensis is also interpretable as demonstrating four ossification centers. A
      new, four-center model for the homology of the amniote astragalus is advanced,
      and is discussed in the context of the phylogeny of the Captorhinidae in an
      attempt to identify the developmental transitions responsible for the observed
      pattern of ossification within this clade. Lastly, the broader implications for
      amniote phylogeny are discussed, concluding that the neomorphic pattern of
      astragalus ossification seen in all extant reptiles (including turtles) arose
      within the clade Diapsida.

PMID- 16421892
TI  - Ethanol-induced alterations of the antioxidant defense system in rat kidney.
AB  - We report here the effects of chronic ethanol consumption on the antioxidant
      defense system in rat kidney. Thirty-two male Wistar rats were randomly divided
      in two identical groups and were treated as follows: control group (water for
      fluid) and the ethanol-fed group (2 g/kg body weight/24 h). The animals were
      sacrificed after 10 weeks, and respectively 30 weeks of ethanol consumption, and
      the renal tissue was isolated and analyzed. Results revealed that kidney alcohol
      dehydrogenase activities increased significantly after ethanol administration,
      but the electrophoretic pattern of alcohol dehydrogenase isoforms was unmodified.
      The SDS polyacrylamidegel electrophoretic study of kidney proteins has revealed
      the appearance of two new protein bands after long-term ethanol consumption. The
      kidney reduced glutathione/oxidized glutathione ratio decreased, indicating an
      oxidative stress response due to ethanol ingestion. The malondialdehyde contents
      and xanthine oxidase activities were unchanged. The antioxidant enzymatic defense
      system showed a different response during the two periods of ethanol
      administration. After 10 weeks, catalase, glutathione peroxidase, glutathione
      reductase, and glucose-6-phosphate dehydrogenase were activated, while superoxide
      dismutase, glutathione transferase, and gamma-glutamyltranspeptidase levels were
      stationary. After 30 weeks, superoxide dismutase and glutathione peroxidase
      activities were unmodified, but catalase, glutathione transferase, gamma
      glutamyltranspeptidase, glutathione reductase, and glucose-6-phosphate
      dehydrogenase activities were significantly increased. Remarkable changes have
      been registered after 30 weeks of ethanol administration for glutathione
      reductase and glucose-6-phosphate dehydrogenase activities, including an increase
      by 106 and 216' of control values, respectively. These results showed specific
      changes in rat kidney antioxidant system and glutathione status as a consequence
      of long-term ethanol administration.

PMID- 16421894
TI  - Warfarin resistance in a French strain of rats.
AB  - A warfarin-resistant strain and a warfarin-susceptible strain of wild rats
      (Rattus norvegicus) maintained in enclosures of the National Veterinary School of
      Lyon (France) were studied to determine the mechanism of the resistance to
      anticoagulant rodenticides. A low vitamin K epoxide reductase (VKOR) activity has
      been reported for many resistant rat strains. As recently suggested, mutations in
      the vitamin K epoxide reductase subunit 1 (VKORC1) gene are the genetic basis of
      anticoagulant resistance in wild populations of rats from various locations in
      Europe. Here we report, for our strain, one of the seven described mutations
      (Tyr139Phe) for VKORC1 in rats. In addition, a low expression of mRNA encoding
      VKORC1 gene is observed in resistant rats, which could explain their low VKOR
      activity. We calculated kinetic parameters of VKOR in the warfarin-resistant and
      warfarin-susceptible rats. The V(max) and the K(m) of the VKOR obtained in
      resistant rats were lowered by 57 and 77%, respectively, compared to those
      obtained in susceptible rats. As a consequence, the enzymatic efficiency
      (V(m)/K(m)) of the VKOR was similar between resistant and susceptible rats. This
      result could be a good explanation to the observation that no clinical signs of
      vitamin K deficiency was observed in the warfarin-resistant strain, while a low
      VKOR activity was found. VKOR activity in warfarin-resistant rats was poorly
      inhibited by warfarin (K(i) for warfarin is 29 microM and 0.72 microM for
      resistant and susceptible rats, respectively).

PMID- 16421893
TI  - Tumor necrosis factor alpha-mediated activation of c-Jun NH(2)-terminal kinase as
      a mechanism for fumonisin B(1) induced apoptosis in murine primary hepatocytes.
AB  - Fumonisin B(1) is a mycotoxin produced by Fusarium verticillioides, frequently
      associated with corn. It produces species-specific and organ-specific toxicity,
      including equine leukoencephalomalacia, porcine pulmonary edema, and hepatic or
      renal damage in most animal species. Fumonisin B(1) perturbs sphingolipid
      metabolism by inhibiting ceramide synthase. Our previous studies indicated that
      fumonisin B(1) caused localized activation of cytokines in liver produced by
      macrophages and other cell types that modulate fumonisin B(1) induced hepatic
      apoptosis in mice. The role of tumor necrosis factor alpha (TNFalpha) in
      fumonisin B(1) mediated hepatocyte apoptosis has been established; not much is
      known about the downstream events leading to apoptosis. In the current study,
      fumonisin B(1) induced apoptosis in primary culture of liver cells. In
      consistence with previous reports, fumonisin B(1) caused accumulation of
      sphingoid bases and led to increase in TNFalpha expression. Phosphorylated and
      total c-Jun NH(2)-terminal kinase (JNK) activities were increased after 24 h
      fumonisin B(1) treatment. JNK inhibitor (SP600125) and anti-TNFalpha reduced the
      apoptosis induced by fumonisin B(1). The role of JNK signaling in fumonisin B(1)
      induced apoptosis is downstream of TNFalpha production, as fumonisin B(1)
      mediated activation of JNK was reduced by the presence of anti-TNFalpha in the
      medium, whereas the presence of JNK inhibitor did not change the fumonisin B(1)
      induced TNFalpha expression. Results of this study imply that generation of
      fumonisin B(1) induced TNFalpha results in modulation of mitogen activated
      protein kinases, particularly of JNK, and provides a possible mechanism for
      apoptosis in murine hepatocytes.

PMID- 16421896
TI  - Malathion detoxification by human hepatic carboxylesterases and its inhibition by
      isomalathion and other pesticides.
AB  - The organophosphorothioate (OPT) pesticide malathion (MAL) in mammals is readily
      hydrolyzed by mammalian carboxylesterases (CE). The reaction competes with the
      CYP-catalyzed formation of malaoxon (MOX), the toxic metabolite. Alterations or
      individual variations in CE activity may result in increased MOX formation,
      enhancing MAL toxicity. We have characterized the human hepatic CE activity in a
      panel of 18 human liver microsomes as well as the inhibitory effect of IsoMAL, a
      major impurity of MAL commercial formulations, parathion (PAR), chlorpyrifos
      (CPF), and chlorpyrifos-oxon (CPFO). CE activity showed a low level of variation
      among individuals (4-fold). The reaction consists of two different phases,
      differing in their affinity for mal (k(m1)=0.25-0.69 microm; K(m2)=10.3-26.8
      microM). The relatively low K(m1) values confirmed that human CE efficiently
      detoxify MAL. IsoMAL was shown to be a potent noncompetitive inhibitor of MAL
      detoxification (K(i)=0.6 microM), with a higher inhibitory potency than CPF and
      PAR (K(i)=7.5 microM and 50 microM, respectively). These two latter compounds
      very likely act as mixed inhibitors. CPFO showed the highest inhibitory potency
      toward CE-mediated detoxification, being characterized by a K(i)=22 nM. The
      present results provide useful information for a better understanding of possible
      interactions between different OPTs and for assessing the potential cumulative
      risk for exposure to OPT mixtures.

PMID- 16421895
TI  - Chemopreventive activity of selenocysteine prodrugs against tobacco-derived
      nitrosamine (NNK) induced lung tumors in the A/J mouse.
AB  - Prodrugs of L-selenocysteine have potential utility in cancer chemoprevention.
      This study reports the efficacy of three selenazolidine-4(R)-carboxylic acids, (2
      unsubstituted, 2-oxo, and 2-methyl derivatives; SCA, OSCA, and MSCA,
      respectively) against tobacco-related lung tumorigenesis in a mouse model. Seven
      days after initiation of an AIN-76A diet supplemented with sodium selenite (5 ppm
      Se), L-selenomethionine (3.75 ppm Se), Se-methyl-L-selenocysteine (3 ppm Se), L
      selenocystine (15 ppm Se), SCA (15 ppm Se), OSCA (15 ppm Se), or MSCA (15 ppm
      Se), mice received 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 10
      micromol, i.p.). After an additional 16 weeks on the diets, two compounds, OSCA
      and selenocystine, significantly reduced lung adenoma multiplicity from 7.2
      tumors per mouse in the NNK group to 4.5 and 4.6 tumors per mouse, respectively.
      Neither selenium concentration nor glutathione peroxidase activity in either RBCs
      or liver served as surrogate indicators of tumor reduction. Hepatic selenium
      levels were significantly elevated by all selenium-containing compounds except Se
      methyl-L-selenocysteine and SCA; RBC selenium levels by all except sodium
      selenite and MSCA. With the exception of L-selenomethionine, RBC glutathione
      peroxidase activity was increased along with the elevated selenium levels.
      Hepatic glutathione peroxidase activity was elevated by all Se-compounds except
      SCA. The two compounds showing significant tumor reduction (OSCA and
      selenocystine) were the only two compounds that showed ubiquity of changes,
      elevating both selenium levels and GPx activity in both liver and RBC.

PMID- 16421897
TI  - Quantification of the expression and inducibility of 12 rat cytochrome P450
      isoforms by quantitative RT-PCR.
AB  - The administration of xenobiotics may significantly alter the expression of
      cytochromes P450 (CYPs), thereby leading to potentially toxic cellular,
      physiologic, and pharmacologic responses. Indeed, an important task in the
      development of new therapeutic entities is to evaluate efficiently and
      quantitatively their potential effects on the expression level of different CYPs.
      In this report, reverse transcriptase polymerase chain reaction (RT-PCR) was used
      to measure basal and induced mRNA of a wide range of rat CYP isoforms. Rats (n=3
      per treatment) were treated with five prototype inducers of CYP isoforms or with
      vehicle only. RT and PCR efficiencies were determined using appropriate RNA and
      DNA standards. Messenger RNA was quantified by PicoGreen standard curves and
      normalized to cyclophilin. Quantitative RT-PCR was used successfully to
      demonstrate that CYP isoforms were induced at the mRNA level following drug
      administration. Notably, phenobarbital resulted in significant induction of
      CYP2B1, CYP2B2, CYP2C6, CYP2C13, CYP2E1, CYP3A1, and CYP3A2. 3-Methylcholanthrene
      induced CYP1A1, CYP1A2, and CYP1B1. CYP2C11 expression was highly variable and
      suppressed by pyridine, whereas the expression of CYP2E1 was suppressed by
      dexamethasone. We demonstrated that quantitative RT-PCR can be used to evaluate
      efficiently the effect of compounds on the expression of a wide range of CYP
      isoforms. The technique is advantageous over others in that it is very sensitive,
      efficient and applicable to highly homologous CYP isoforms.

PMID- 16421899
TI  - Childhood acute lymphoblastic leukaemia in relation to population mixing around
      the time of birth in South Hungary.
AB  - In a retrospective epidemiological study of 481,984 live births in South Hungary,
      we investigated whether higher levels of population mixing around the time of
      birth is a risk factor for acute lymphoblastic leukemia (ALL) under age 5 years.
      Poisson regression was used to investigate the relationship between risk of ALL
      and the population-mixing index based on the number of incomers in each county
      district for each year, standardized to have a range of 0-1. Among all children,
      the risk of ALL increased significantly with increasing population mixing around
      the time of birth (trend across the range of 0-1 RR = 2.1 95% CI: 1.02-4.44).
      This effect was more marked for boys (RR = 3.1 95% CI: 1.13-8.51), which supports
      a sex-specific effect of exposures on risk of ALL.

PMID- 16421900
TI  - EBV lymphoproliferative disease of host origin after haploidentical stem cell
      transplantation.
AB  - Post-transplant lymphoproliferative disease (PTLPD), due to the reactivation of
      Epstein-Barr virus (EBV), is a serious complication. The risk of the disorder
      increases with T-cell depletion methods, mismatched hematopoietic stem cell
      transplantation (HSCT), graft-versus-host disease (GVHD), and immunosuppression.
      In contrast to solid organ transplantation, where EBV is typically of recipient
      origin, the source of the EBV in HSCT recipients is donor-derived B-lymphocytes.
      In this report, we describe a 15-year-old girl who underwent HSCT from her father
      as treatment for acute myeloid leukemia (AML). She subsequently developed
      disseminated PTLPD involving multiple organ and nodal sites. Her neoplastic
      lymphoblasts were host-derived and refractory to rituximab treatment due to lack
      of CD20 expression.

PMID- 16421901
TI  - Evaluation of health status and health-related quality of life in a cohort of
      Italian children following treatment for a primary brain tumor.
AB  - BACKGROUND: This study is a pilot experience aiming to investigate the compliance
      of an institutional cohort of Italian children treated for a malignant disease
      and their families in completing the health utilities index2, (HUI2) and the
      effectiveness of this measured in terms of their health status (HS) and health
      related quality of life (HRQL). It specifically, it aimed to compare the HS and
      the HRQL, as expressed by the HUI2 global utility score, in cohorts of patients
      who had brain tumors, extra-cerebral solid tumors, or leukemia/lymphoma.
      PROCEDURE: Fifty survivors of brain tumors, between 8 and 30 years at the time of
      the assessment ("self") and/or their parents ("proxy"), attending the Pediatric
      Oncology Out Patient clinic of Padua, Italy, completed the HUI2 questionnaire.
      Eighty-nine children with acute leukemia/lymphoma and 74 with extra-cerebral
      solid tumors and/or their parents were also assessed. RESULTS: The mean "self"
      and "proxy" HUI2 global utility scores in the brain tumor patients were 0.87 and
      0.84, respectively, while in the cohorts of children with other solid tumors and
      leukemia/lymphoma, there were 0.94, 0.91, 0.96, and 0.92, respectively. The
      differences between the HUI2 global utility scores in the "self" and "proxy"
      assessment within each cohort of children were not statistically significant. In
      decreasing order of frequency, the attributes affected most commonly were:
      "emotion," "pain," "sensation," and "cognition" both by "self" and "proxy"
      assessment. CONCLUSIONS: In this Italian population of childhood cancer survivors
      the HUI2 questionnaire proved to be a user-friendly tool, which provided
      information regarding HS and HRQL. A larger cohort of cancer children is needed
      to confirm the efficacy of the HUI2 questionnaire in distinguishing groups of
      children on this basis by disease category.

PMID- 16421902
TI  - Effects of human monoclonal antibody 216 on B-progenitor acute lymphoblastic
      leukemia in vitro.
AB  - BACKGROUND: Human monoclonal antibody (mAb) 216 is a naturally occurring IgM
      cytotoxic mAb that binds to a glycosylated epitope on the surface of B
      lymphocytes. This study investigated if this mAb could bind and kill acute
      lymphoblastic leukemia (ALL) B-progenitor lymphoblasts in vitro. ALL cell lines
      were used to determine if combining mAb 216 with chemotherapeutic drugs would
      enhance killing and cell lines were used to measure cytotoxicity by mAb 216 with
      human complement. PROCEDURE: Expression of cell surface markers and mAb 216
      epitope on fresh and banked ALL bone marrow samples was determined by flow
      cytometry. Fresh lymphoblasts were incubated for 20 hr with mAb 216 without
      complement to measure cytotoxicity. Cytotoxicity of ALL cell lines incubated with
      mAb 216 and vincristine (VCR) or human complement was determined using flow
      cytometry. RESULTS: Pre-B-ALL cells but not T-ALL cells are bound and killed by
      mAb 216. The combination of mAb 216 and VCR at sub-therapeutic levels
      demonstrated enhanced cytotoxicity beyond that observed for either agent alone.
      Incubation of mAb 216 with human complement increased cytotoxicity of ALL cell
      lines. CONCLUSION: This increased cytotoxicity with chemotherapy and the
      functional ability of mAb 216 to use multiple pathways to induce cell death
      identify mAb 216 as a potentially novel therapeutic tool in the treatment of B
      progenitor ALL. Based on the results from this preclinical study, a Phase I
      clinical trial with mAb 216 for the treatment of patients with relapsed or
      refractory B-lineage ALL is ongoing.

PMID- 16421903
TI  - Eliminating a gold standard in childhood acute lymphoblastic leukemia?

PMID- 16421904
TI  - Inhibition of Ih reduces epileptiform activity in rodent hippocampal slices.
AB  - Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels regulate
      membrane potential, neurotransmitter release, and patterning of synchronized
      neuronal activity. Currently, there is an intense debate as to whether or not
      these ion channels play a pro- or anticonvulsant role in vivo. To gain an insight
      into this question, we have examined how inhibitors of the response mediated by
      HCN channels (referred to as I(h)) affect epileptiform activity induced in adult
      hippocampal slices. The archetypal I(h) blocker ZD-7288 produced a concentration
      dependent inhibition of both nonsynaptic- (low Ca(2+)/elevated K(+) aCSF) and
      synaptic- (low Mg(2+) aCSF, elevated K(+) aCSF or convulsant application
      (bicuculline or pentylenetetrazol)) based epileptiform activities. The IC(50)
      value for ZD-7288 induced inhibition of epileptiform activity was similar across
      all forms of epileptiform response and was below concentrations producing
      nonspecific inhibition of glutamatergic synaptic transmission. Furthermore,
      capsazepine, which exhibits similar potency to ZD-7288 at inhibiting I(h), failed
      to inhibit glutamatergic synaptic transmission per se but produced a significant
      inhibition of bicuculline-induced epileptiform activity. These data suggest that
      broad spectrum inhibition of I(h) reduces neuronal hyperexcitability in the
      hippocampus.

PMID- 16421905
TI  - Hypothyroidism alters striatal dopamine release mediated by 3,4
      methylenedioxymethamphetamine (MDMA, ecstasy).
AB  - Microdialysis cannulas were surgically implanted into the striatum of
      thyroparathyroidectomized (TX) and sham rats in order to determine differences in
      dopamine release and core body temperature following MDMA administration. Rats
      were subsequently treated with MDMA (10 mg/kg, s.c.), and striatal DA levels were
      monitored at 20 min intervals, as well as core temperature every 30 min. Sham
      rats responded to MDMA with a characteristic hyperthermic response and
      significant increases in extracellular dopamine. Conversely, TX rats responded to
      MDMA with a hypothermic response and failed to demonstrate a similar increase
      from basal dopamine levels. On the basis of these data, thyroid hormones are not
      only important in the thermogenic effects of MDMA but also appear to have an
      auxiliary role in MDMA-induced striatal dopamine release.

PMID- 16421906
TI  - High-dose cyclophosphamide inhibition of humoral immune response to murine
      monoclonal antibody 3F8 in neuroblastoma patients: broad implications for
      immunotherapy.
AB  - BACKGROUND: The murine monoclonal antibody 3F8 mediates lysis of neuroblastoma
      (NB) by complement and leukocytes (including neutrophils) but is neutralized if
      human anti-mouse antibody (HAMA) forms. We assessed the impact on rapid HAMA
      formation of prior chemotherapy in NB patients. METHODS: For the 153 patients
      treated with 3F8 after conventional therapy (Group 1), the analysis included time
      from chemotherapy to the start of 3F8. For the 103 patients treated with 3F8
      after myeloablative alkylator-based therapy (MAT) (Group 2), the analysis
      included both chemotherapy administered before stem-cell collection and time from
      MAT to the start of 3F8. RESULTS: In Group 1, the incidence of HAMA-positivity
      was significantly lower if patients received high-dose cyclophosphamide (HD-Cy, >
      or = 4,000 mg/m2) before 3F8 treatment (P < 0.001). In addition, HAMA-positivity
      was least likely if 3F8 treatment was initiated <90 days post-HD-Cy (2/76
      compared to 3/19 first treated at 90-120 days, and 17/27 first treated at >120
      days, P < 0.001). In Group 2 patients who were transplanted with stem cells
      collected after HD-Cy, HAMA-positivity occurred in 1/60 patients treated <90 days
      post-MAT versus 13/23 treated >90 days post-MAT (P < 0.001). Among Group 2
      patients transplanted with stem cells collected after no prior HD-Cy, the
      incidence of HAMA-positivity was significantly higher (15/19, P < 0.001),
      including 5/7 whose 3F8 treatment began <90 days post-MAT. CONCLUSIONS: HD-Cy
      reliably blocks humoral responses to a murine antibody. This capacity to prevent
      host rejection of foreign or not fully humanized proteins raises the possibility
      of a broad role for HD-Cy in immunotherapeutic strategies.

PMID- 16421907
TI  - Quantitative bone mineral density assessment in malignant infantile
      osteopetrosis.
AB  - PURPOSE: To investigate the use of quantitative computed tomography (QCT) and
      dual energy absorptiometry (DXA) for assessing bone mineral density (BMD) in the
      evaluation of children with malignant infantile osteopetrosis (MIOP). METHODS AND
      PATIENTS: We retrospectively reviewed QCT- and DXA-determined BMD in six patients
      with infantile osteopetrosis and correlated BMD measured during the initial
      evaluation with patient characteristics. RESULTS: Five male and one female infant
      met the eligibility criteria. BMD was markedly elevated in all patients as
      determined by each modality, QCT or DXA. For QCT, in which age-specific normal
      values are known, the BMD was found to be 22.4-32.6 standard deviations above the
      mean. Using DXA, the estimated BMD of the lumbar spine ranged from 0.45 to 0.8
      g/cm(2); children with similarly appearing bone radiographs had quite disparate
      BMD. While the qualitative trend of BMD among the patients was similar for both
      measures, the units and numerical values of BMD differed. We found no correlation
      between BMD results and hematopoiesis observed in the bone marrow or with visual
      evaluation of the radiographs. CONCLUSION: Both QCT and DXA are effective
      quantitative measures of BMD in children with MIOP. However, the same modality
      should be employed for longitudinal evaluation of a given patient. Each technique
      has unique advantages and disadvantages and may complement one another in the
      evaluation of MIOP or other bone disorders. Quantitative assessment of BMD in
      children with MIOP will likely serve to further characterize this disease.

PMID- 16421908
TI  - Low prevalence of complications in severe neutropenic children with cancer in the
      unprotected environment of an overnight camp.
AB  - BACKGROUND: The high risk of infection and other complications in severely
      neutropenic pediatric oncology patients receiving chemotherapy has led to
      development of a variety of preventive measures including isolation and diet
      restrictions. In order to examine the potential impact of these measures, we
      evaluated the outcomes of such patients attending a recreational summer camp.
      METHODS: We collected data on all children who attended an overnight summer camp
      for children with cancer during the years 1999-2004, and who were either severely
      neutropenic or at a high-intensity phase of chemotherapy. Outcome measures
      included fever, bleeding, hospitalization, and clinical or laboratory evidence of
      infection. The observation period included both, the 2-week camp experience and
      30 days post-camp. RESULTS: The study group was comprised of 34 patients.
      Although nine (24%) were hospitalized for management of fever and neutropenia,
      only one patient had clinical or culture-positive evidence of an invasive
      infectious agent. No bleeding episode was recorded and most patients attended all
      camp activities. CONCLUSIONS: Our results support the safety and feasibility of
      severely neutropenic patients with cancer to attend the non-isolated, non-sterile
      environment of a summer camp. These findings may be applicable to school and
      other social settings.

PMID- 16421909
TI  - An analysis of primary site control and late effects according to local control
      modality in non-metastatic Ewing sarcoma.
AB  - PURPOSE: To examine prognostic factors for primary site control and analyze late
      effects according to local treatment modality in non-metastatic Ewing sarcoma
      (ES). MATERIALS AND METHODS: From 1976 to 2001, 76 patients with localized ES and
      a median age of 14.5 years were seen and treated at one institution. Tumors were
      located in the extremity in 38, pelvis in 13, spine in 11, trunk in 8, and head
      and neck in 6. Tumor size was < or = 8 cm in 44 and >8 cm in 32. Local therapy
      included radiotherapy (RT) alone in 40, surgery (S) alone in 27, and surgery
      followed by postoperative radiotherapy (S + RT) in 9. Chemotherapy (CT) was
      delivered to 65 patients (86%). Median follow-up for surviving patients was 9.7
      years. RESULTS: The 5- and 10-year overall survival rates were 57.5% and 52.1%
      while the 5- and 10-year local control rate was 79.2%. The 5- and 10-year local
      control rates were 78.2% for RT, 77.6% for surgery, and 88.9% for S + RT (P =
      0.68). Multivariate analysis showed that only the use of CT was found to be a
      prognostic factor for local control (P = 0.014). The 5- and 10-year local control
      rates were 83.7% for those receiving CT and 51.1% for those not receiving CT. For
      patients followed at least 5 years from diagnosis, late effects were seen in 10
      of 19 (52.6%) receiving RT, 2 of 5 (40%) receiving S + RT, and 4 of 16 (25%)
      receiving surgery alone. The most common late effects with RT were muscular
      atrophy, limb length growth delay, and development of second malignancy.
      Scoliosis and decrease range of motion of an extremity were seen regardless of
      local treatment modality. Three patients who had surgery alone had an amputation
      whereas two who had RT had an amputation secondary to relapse or development of
      osteosarcoma. CONCLUSION: In this single institution study, the use of CT was the
      only factor found to impact on local control. Late effects were common regardless
      of local control strategy.

PMID- 16421911
TI  - Increased incidence of malignancies in Sweden after the Chernobyl accident--a
      promoting effect?
AB  - BACKGROUND: After the Chernobyl accident in 1986, as much as 5% of the released
      caesium-137 was deposited in Sweden due to a heavy rainfall 2 days after the
      event. A study of increased incidence of malignancies was initiated after the
      accident. METHODS: The cohort included 1,137,106 inhabitants who were 0-60 years
      old in 1986 and lived in 8 counties of Sweden with the highest fallout of caesium
      137. With the dwelling coordinate, GIS-technique and a digital map on caesium
      137, each individual was matched for the exposure. Adjustments were made for
      several potential confounding factors. During the follow-up 33,851 malignancies
      was recorded 1988-1999. RESULTS: Exposure categories were: 0-8 (reference), 9-23,
      24-43, 44-66, 67-84, and > or =85 nGy/hr. The corresponding adjusted Mantel
      Haenszel incidence rate ratios for total malignancies during follow-up amounted
      to 1.000, 0.997, 1.072, 1.114, 1.068, 1.125, respectively. The excess relative
      risk per 100 nGy/hr with the same adjustments and time period was 0.042 95%
      confidence limit 0.001;0.084. An excess for thyroid cancer or leukemia could not
      be ruled out. CONCLUSION: Increased incidence of total malignancies possibly
      related to the fallout from the Chernobyl accident is seen.

PMID- 16421912
TI  - Long-lasting partial remission by Interferon-alpha treatment in a child with
      essential thrombocythemia.
AB  - Essential thrombocythemia (ET) is a clonal myeloproliferative disorder
      characterized by sustained thrombocytosis, isolated hyperplasia of megakaryocytic
      lineage, and association with thrombotic or bleeding episodes. It is extremely
      rare in childhood and frequently presents without evident clinical signs. We
      describe a 3-year-old girl with severe headache and dizziness suffering from ET,
      who was treated with Interferon-alpha-2a (IFN) based on the potent effect of this
      agent to inhibit myeloid colonies induced by phytohemagglutinin A stimulated
      leukocyte conditioned medium (PHA-LCM). Bone-marrow-derived mononuclear cells of
      this patient did not exhibit spontaneous colony formation but responded to
      recombinant human (rh) erythropoietin (EPO), rh granulocyte-colony stimulating
      factor (G-CSF), granulocyte-macrophage (GM)-CSF, and stem-cell factor in addition
      to PHA-LCM. After 65 months of in vivo IFN treatment, the patient experienced a
      sustained partial remission with platelet counts varying between 400 and 600 x
      10(3)/microl.

PMID- 16421910
TI  - Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric
      (ALL97) and adult (UKALLXII/E2993) trials.
AB  - BACKGROUND: Adolescents with acute lymphoblastic leukaemia (ALL) have languished
      in the shadow of success of the outcome of therapy in childhood ALL. Their
      treatment has always been incorporated into either paediatric or adult clinical
      trials depending on the mode of referral and hence there is a need to address an
      age and risk specific strategy for improving the outcome of this neglected group
      of patients. This article has summarised the recent and updated retrospective
      comparative analysis of adolescents treated on the Medical Research Council (MRC)
      trials. This analysis adds further emphasis to the treatment approach and the
      merits and limitations of treatment of adolescents on paediatric and adult
      trials. METHODS: A retrospective comparative analysis of adolescents aged 15-17
      years, treated on either MRC ALL97/revised 99 (n = 61), a randomised paediatric
      trial or UKALLXII/E2993 (n = 67), an adult trial, between 1997 and 2002 was
      undertaken. RESULT: Results suggest a trend towards a superior outcome on
      paediatric trials. The 5-year EFS on ALL97 was 65% (95% CI = 52-78%) and on
      UKALLXII/E2993 was 49% (95% CI = 37-61%; P = 0.01). Multivariate analysis
      allowing for age and Ph status, diminished the EFS difference, but confirmed a
      reduced rate of death in remission in patients managed on the paediatric
      protocol. CONCLUSIONS: Despite limitations in the methodology, comparative
      studies including our MRC study suggest a consistent advantage for adolescents
      managed intensively on paediatric trials. Redefining age limits with risk-based
      strategy and multi-centre collaboration should be considered to improve the
      survival of young adults.

PMID- 16421913
TI  - Extracorporeal membrane oxygenation (ECMO) initiation without intubation in two
      children with mediastinal malignancy.
AB  - We report the cases of two children presenting with severe airway compromise
      secondary to a mediastinal malignancy managed with extracorporeal membrane
      oxygenation without intubation. Results are presented on the use of ECMO as a
      primary means of stabilizing a pediatric patient with a critical mediastinal
      mass, thus providing another management strategy for this difficult situation.

PMID- 16421914
TI  - Identification of single eukaryotic cells with micro-Raman spectroscopy.
AB  - For a fast identification of eukaryotic cells such as yeast species without a
      cultivation step it should be possible to perform the investigation on only one
      single cell. Since yeasts as eukaryotes are heterogeneous and their Raman spectra
      are therefore dependent on the measuring position, one Raman spectra is not
      representative of the whole cell. In this contribution we demonstrate the
      application of average Raman spectra of a line scan over single yeast cells.
      These average spectra are used for classification with the help of a support
      vector machine.

PMID- 16421915
TI  - Surface-enhanced Raman scattering study of the interaction of red dye alizarin
      with ovalbumin.
AB  - Surface-enhanced Raman spectroscopy and UV-vis absorption spectroscopy were
      employed to study the interaction between the red dye alizarin and ovalbumin
      (OA), to check the effect of binding media usually employed when applying this
      pigment in painting practices based on egg tempera. The protein/alizarin
      interaction is rather weak and takes place through the alizarin neutral form,
      which interacts with exposed hydrophobic moieties of OA. This effect is of great
      interest from an artistic point of view because the dye color can be modified.
      Furthermore, the interaction with alizarin could induce a change in the protein
      structure, leading to a denaturation and subsequent aggregation.

PMID- 16421916
TI  - Single seed Raman measurements allow taxonomical discrimination of Apiaceae
      accessions collected in gene banks.
AB  - NIR-FT-Raman spectroscopy was applied for a nondestructive analysis of single
      seeds (fruit mericarps) of 36 accessions belonging to various species of the
      Apiaceae family. Main seed components such as fatty acids, polysaccharides,
      proteins, and lignin were identified based on the obtained Raman spectra.
      Variation at the species and genus level was related to differences observed
      between spectra. The application of cluster analysis discriminated among most of
      the species evaluated and grouped them according to their taxonomical
      classification. The spectroscopically analyzed seeds germinated and developed
      into normal seedlings to demonstrate the additional advantage that Raman
      spectroscopy is nondestructive and can be applied to living seed without harm.
      These results indicate that Raman spectroscopy is a valuable tool for the
      rational evaluation and management of genetic resources in ex situ seed
      collections by providing useful information for taxonomical validation of the
      accessions.

PMID- 16421917
TI  - Needlestick and sharps injuries among a cross-section of physicians in Mainland
      China.
AB  - BACKGROUND: Although needlestick and sharps injuries (NSI) represent a
      significant occupational hazard for physicians worldwide, their epidemiology has
      not been previously examined in Mainland China. This study describes the
      prevalence, distribution, and risk factors for NSI among a cross-section of
      Chinese physicians. METHODS: Data was obtained by an anonymous, self-reporting
      survey administered to all 361 physicians at a university teaching hospital,
      during 2004. RESULTS: Seventy-nine percent of the physicians responded. Among
      them, 64% had experienced an NSI in the previous 12 months, 50.3% of which
      involved contaminated devices. By device, 22.8% were caused by hollow-bore
      syringe needles, 19.1% by suture needles, and 12.1% by scalpel blades. Surgical
      procedures accounted for 27.9% of all injuries. Only 15.3% of physicians had
      officially reported their NSI to management, of which 10% went unreported because
      the individual felt they were not unlucky enough to get a disease. A
      statistically significant correlation was demonstrated between NSI and working in
      the intensive care unit (adjusted odds ratio: 5.3, 95% CI: 1.7-23.4).
      CONCLUSIONS: Although this study suggests that NSI are an important workplace
      hazard for Chinese physicians, future measures should consider the unique
      cultural beliefs of Chinese people and its effect on preventive behaviors. The
      concept of "luck," and its relationship with NSI reporting in particular, may
      also need to be addressed.

PMID- 16421918
TI  - A study of factors influencing return to work after wrist or ankle fractures.
AB  - BACKGROUND: Factors associated with time to return to work are poorly understood
      for occupational injuries, other than those to the back. METHODS: Anonymized data
      on claims for work-related wrist or ankle fracture between 1/1/1998 and
      12/31/2002 were identified in administrative data held by the Workers
      Compensation Board in Alberta, Canada. Bivariate and Cox regression analyses were
      used to identify factors associated with return to work. RESULTS: Increased
      duration of temporary disability (TD) was associated with older age, female
      gender, work in construction and construction trade services, smaller company
      size, higher industry claim rates, a fall/jump from a height, ankle fracture, and
      greater medical aid costs in the 30 days following injury (used as a proxy for
      severity). CONCLUSIONS: Factors associated with longer time off work were largely
      consistent with those reported following back injury. Median time to return to
      work was longer following ankle than wrist fracture. Although Workers'
      Compensation Board (WCB) administrative data provided information that could be
      used to identify factors affecting return to work, better information on injury
      severity would considerably enhance their research potential.

PMID- 16421919
TI  - Thermodynamic properties of Ag2O--B2O3 glasses by a modified scale-transformed
      energy space sampling Monte Carlo method.
AB  - The density of states of Ag(2)O--B(2)O(3) glasses has been calculated by using a
      modified scale-transformed energy space sampling algorithm. This algorithm
      combines the scale-transformed energy space sampling algorithm and the Wang
      Landau method. It is shown how the two algorithms can be combined to improve the
      efficiency of calculation. The thermodynamic properties, in particular the
      specific heat C(V), of the above-mentioned glass system is studied. At
      temperatures above 80 K, the value of specific heat C(v) is close to 22 J/mol/K.
      At low temperatures, the deviations of C(v) from a T(3) behavior are discernible,
      that is, C(v)/T(3) exhibits a hump at T = 7 K, which is in good agreement with
      the reported experimental behavior.

PMID- 16421920
TI  - Distribution of human papillomavirus types in ThinPrep Papanicolaou tests
      classified according to the Bethesda 2001 terminology and correlations with
      patient age and biopsy outcomes.
AB  - BACKGROUND: A survey of the distribution of human papillomavirus (HPV) types
      across the spectrum of cervical cytologic categories defined by the Bethesda 2001
      guidelines was conducted with the objective of examining how HPV detection by
      polymerase chain reaction (PCR) analysis may benefit the management of patients
      who have abnormal Papanicolaou (Pap) test results. METHODS: DNA samples from
      women with no intraepithelial lesion or malignancy (NLM) (n = 300 samples);
      atypical squamous cells of undetermined significance (ASC-US) (n = 200 samples);
      low-grade squamous intraepithelial lesion (LSIL) (n = 200 samples); atypical
      squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC
      H) (n = 200 samples); and high-grade squamous intraepithelial lesion (HSIL) (n =
      200 samples) were tested for HPV using a modified general primer (GP)5+/GP6+ PCR
      assay and dot-blot hybridization with type-specific oligonucleotide probes (PCR
      assay analytical sensitivity: 1-100 copies of HPV, depending on the HPV type, in
      a background of 100 ng human DNA). RESULTS: HPV was detected in 27% of NLM
      samples, in 89.5% of ASC-US samples, in 97.5% of LSIL samples, in 93% of ASC-H
      samples, and in 96.5% of HSIL samples. Thirty-seven different HPV types were
      identified in total. One or more of 13 high-risk (HR) HPV types (16, 18, 31, 33,
      35, 39, 45, 51, 52, 56, 58, 59, and 68) were detected in 53% of samples that were
      diagnosed as ASC-US (59.0% of patients younger than age 30 yrs; 45.5% of patients
      age 30 yrs and older), in 55.5% of samples that were diagnosed as LSIL (60.0% of
      patients younger than age 30 yrs; 44.0% of patients age 30 yrs and older), in 80%
      of samples that were diagnosed as ASC-H, and in 87.5% of samples that were
      diagnosed as HSIL (P < 0.001). HPV-16 was detected in 17.5% of ASC-US samples, in
      15.5% of LSIL samples, in 48.5% of ASC-H samples, and in 49.0% of HSIL samples (P
      < 0.001). Among abnormal smears, HR HPV was significantly more common in women
      younger than age 30 years compared with women age 30 years and older (P < 0.002).
      Follow-up biopsy data were obtained for 359 patients. A "benign" biopsy result
      was recorded for 47 of 64 women (73.5%) with ASC-US, 30 of 66 women (45.5%) with
      LSIL, 39 of 87 women (45.0%) with ASC-H, and 26 of 142 women (18.0%) with HSIL
      and was most common in women age 30 years and older (P < 0.0001). Cervical
      intraepithelial neoplasia (CIN) Grade I (CIN-I) was found in 14.0% of women with
      ASC-US, in 39.5% of women with LSIL, in 8.0% of women with ASC-H, and in 7.0% of
      women with HSIL. CIN-II was diagnosed in 9.5% of women with ASC-US, in 13.5% of
      women with LSIL, in 19.5% of women with ASC-H, and in 24.0% of women with HSIL.
      CIN-III was identified in 2 women (3.0%) with ASC-US, in 1 woman (1.5%) with
      LSIL, in 24 women (27.5%) with ASC-H, and in 71 women (50.0%) with HSIL.
      CONCLUSIONS: HR HPV testing by PCR of samples diagnosed according to the Bethesda
      2001 guidelines may benefit the management of patients with ASC-US or patients
      with LSIL, especially among women age 30 years and older, by allowing exclusion
      from referral for biopsy of women who are negative for HR HPV types. However, the
      small numbers of women who had CIN-III detected after a diagnosis of ASC-US or
      LSIL limited the assessment of test sensitivity.

PMID- 16421921
TI  - In utero exposure to female hormones and germ cell tumors in children.
AB  - BACKGROUND: Maternal exposure to exogenous female hormones during pregnancy has
      been implicated as a risk factor for malignant germ cell tumors (GCTs) in the
      offspring in some epidemiologic studies of testicular and ovarian carcinoma in
      adults. METHODS: From 1996 to 2002, 278 children younger than 15 years of age
      with malignant GCTs and 423 healthy controls, frequency-matched for geographic
      location, age, and sex were enrolled in a case-control study to investigate
      whether in utero exposure to female hormones is associated with the risk of
      malignant GCT in children. Cases were recruited from 84 institutions in the U.S.
      and controls were enrolled through random digit dialing. Information was obtained
      through telephone interview with the biological mothers of the subjects and
      through blinded review of the mothers' medical records. RESULTS: Neither self
      reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor
      medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to
      exogenous female hormones was related to malignant GCT risk. Pregnancy-related
      conditions that may have altered serum levels of circulating female hormones were
      also unrelated to the risk of GCT in the offspring. CONCLUSION: This study failed
      to provide strong evidence to support the hypothesis that maternal exposure to
      exogenous female hormones during pregnancy increases the risk of GCT in the
      offspring.

PMID- 16421922
TI  - Long-term cosmetic results and toxicity after accelerated partial-breast
      irradiation: a method of radiation delivery by interstitial brachytherapy for the
      treatment of early-stage breast carcinoma.
AB  - BACKGROUND: The objective of this study was to assess the cosmesis and toxicities
      in patients with early-stage breast carcinoma who received treatment with
      accelerated partial breast irradiation (APBI) using interstitial brachytherapy.
      METHODS: From April 1993 to December 2001, 199 patients with Stage I-II breast
      carcinoma received breast-conserving therapy with APBI to the tumor bed alone
      through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide
      was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant
      delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis
      (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines)
      were assessed at < or = 6 months, 2 years, and 5 years. RESULTS: The median
      follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all
      diminished over time. Breast fibrosis and hypopigmentation increased until the 2
      year mark and then stabilized. Fat necrosis and telangiectasia increased over
      time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34%
      at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all
      follow-up intervals. Infections (11%) occurred predominantly within the first
      month after treatment. Good-to-excellent cosmetic outcomes were noted in 95-99%
      of patients over time; cosmetic results stabilized at 2 years with excellent
      results increased out to 5 years. CONCLUSIONS: APBI with interstitial
      brachytherapy resulted in mild chronic toxicities, the majority of which
      diminished or reached a plateau over time. Long-term cosmesis was good to
      excellent in 95-99% of patients and stabilized at 2 years.

PMID- 16421923
TI  - Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant
      chemotherapy: 15-year experience in 789 patients treated at a single institution.
AB  - BACKGROUND: The evaluation variables influencing systemic and local recurrence
      and final outcome are extremely important in defining risk-adapted treatments for
      patients with nonmetastatic osteosarcoma of the extremity. METHODS: A homogeneous
      group of 789 patients treated at a single institution between March 1983 and
      March 1999 with different protocols of neoadjuvant chemotherapy, with a minimum
      followup of 5 years, were retrospectively evaluated in relation to gender, age,
      serum levels of alkaline phosphatase, tumor site and size of the pathologic
      fracture, type of surgery, protocol of chemotherapy, surgical margins, and
      histologic response to preoperative treatment. RESULTS: The 5-year event-free
      survival (EFS) and overall survival rates were 60.1% and 67.5%, respectively.
      Upon univariate analysis, EFS was significantly related to the age of patients,
      serum value of alkaline phosphatase, tumor volume, histologic subtype, type of
      surgery, surgical margins, histologic response to preoperative treatment, and
      chemotherapy protocol. Local recurrences (4.8%) were significantly correlated
      with surgical margins. The 5-year post-recurrence EFS survival was 17% and was
      significantly lower for patients who had a local recurrence and metastases than
      for those with metastases only. Patients who had a recurrence only in the lung
      had a post-recurrence survival rate significantly better than others, correlated
      with the number of metastatic nodules and the length of the disease-free
      interval. CONCLUSIONS: Upon multivariate analysis, age < or = 14 years, high
      serum levels of alkaline phosphatase, tumor volume > 200 mL, a two-drug regimen
      chemotherapy, inadequate surgical margins, and poor histologic response to
      treatment maintained independent prognostic values on the outcome of
      nonmetastatic osteosarcoma of the extremities. These factors must be considered
      when deciding risk-adapted treatments for osteosarcoma patients.

PMID- 16421924
TI  - CSF-1 and PI 3-kinase regulate podosome distribution and assembly in macrophages.
AB  - Podosomes are actin-rich adhesive foci found in several cell types, including
      macrophages. They have a core containing actin and actin-binding proteins and a
      peripheral ring of integrins and associated proteins. We show that podosomes are
      abundant in polarized mouse bone marrow-derived macrophages (BMM) and are found
      primarily in lamellae. We investigated the effects of CSF-1, which induces
      membrane ruffling, cell spreading, and subsequent polarization and migration, on
      podosome formation. CSF-1 induces a transient increase in podosome number and
      enhances the formation of circular arrays of podosomes. Conversely, CSF-1
      withdrawal leads to a reduction in podosomes and a decrease in polarized cells.
      The PI 3-kinase inhibitor LY294002 induces loss of podosomes together with rapid
      retraction of lamellae and loss of polarity. Our results indicate that CSF-1 acts
      via PI 3-kinase to enhance podosome assembly and that this is linked to
      macrophage polarization.

PMID- 16421925
TI  - Craniofacial morphology in the Argentine Center-West: consequences of the
      transition to food production.
AB  - The Argentine Center-West was the southernmost portion of the Andes where
      domestication of plants and animals evolved. Populations located in the southern
      portion of this area displayed a hunter-gatherer subsistence economy up to
      historical times, and coexisted with farmers located to the north. Archaeological
      and biological evidence suggests that the transition to food production was
      associated with the consumption of a softer diet and a more sedentary way of
      life. This study tests the hypothesis that diet-related factors influenced
      morphological differentiation, by comparing functional cranial components of
      farmers and hunter-gatherers. Three-dimensional changes on eight minor functional
      components (anteroneural, midneural, posteroneural, otic, optic, respiratory,
      masticatory, and alveolar) were measured on skulls derived from both subareas.
      Volumetric and morphometric indices were calculated to estimate the absolute and
      relative size of components, respectively. Results of a paired t-test indicated
      that farmers have a smaller craniofacial size than hunter-gatherers. The
      components that varied the most were masticatory and posteroneural, showing
      smaller absolute and relative sizes in farmers. Discriminant analyses indicated
      that lengths and widths were the most affected dimensions of these and other
      components. The pattern of differentiation, which involves specific components,
      enabled us to exclude differential gene flow and stochastic mechanisms as the
      main causes. Instead, results support the hypothesis that diet-related factors
      associated with both subsistence economies influenced craniofacial morphology. A
      proportion of the observed variation associated with size differences can be
      explained by two systemic factors: the lesser quality of nutrition due to a low
      protein content in the diet, and a decrease of growth hormone circulation induced
      by a lower mobility due to sedentism. However, differentiation is better
      explained by a localized factor: the reduction in the masticatory and
      posteroneural components in farmers resulted from a decrease of masticatory
      stresses and workload on the head and neck, linked to the consumption of a softer
      diet.

PMID- 16421926
TI  - A critical role for the type V myosin, Myo52, in septum deposition and cell
      fission during cytokinesis in Schizosaccharomyces pombe.
AB  - Cytokinesis in fission yeast involves the coordination of septum deposition with
      the contraction of a cytokinetic actomyosin ring. We have examined the role of
      the type V myosin Myo52 in the coupling of these two events by the construction
      of a series of deletion mutants of the Myo52 tail and a further mutant within the
      ATP binding domain of the head. Each mutant protein was ectopically expressed in
      fission yeast cells. Each truncation was assayed for the ability to localize to
      the cell poles and septum (the normal cellular locations of Myo52) and to rescue
      the morphology defects and temperature sensitivity of a myo52Delta strain. A
      region within the Myo52 tail (amino acids 1320-1503), with a high degree of
      similarity to the vesicle-binding domain of the budding yeast type V myosin
      Myo2p, was essential for Myo52's role in the maintenance of growth polarity and
      cell division. A separate region (amino acids 1180-1320) was required for Myo52
      foci to move throughout the cytoplasm; however, constructs lacking this region,
      but which retained the ability to dimerize still associated with actin at sites
      of cell growth. Not all of the Myo52 truncations which localized rescued the
      morphological defects of myo52Delta, demonstrating that loss of function was not
      simply brought about by an inability of mutant proteins to target the correct
      cellular location. By contrast, Myo52 motor activity was required for both
      localization and cellular function. myo52Delta cells were unable to efficiently
      localize the beta-1,3-glucan synthase, Bgs1, either at the cell poles or at the
      division septum, regions of cell wall deposition. Bgs1 and Myo52 localized to
      vesicle-like dots at the poles in interphase and these moved together to the
      septum at division. These data have led to the formulation of a model in which
      Myo52 is responsible for the delivery of Bgs1 and associated molecules to polar
      cell growth regions during interphase. On the commencement of septum formation,
      Myo52 transports Bgs1 to the cell equator, thus ensuring the accurate deposition
      of beta-1,3-glucan at the leading edge of the primary septum.

PMID- 16421927
TI  - Rho signaling in Entamoeba histolytica modulates actomyosin-dependent activities
      stimulated during invasive behavior.
AB  - Interaction of Entamoeba histolytica trophozoites with target cells and
      substrates activates signaling pathways in the parasite. Phosphorylation cascades
      triggered by phospho-inositide and adenyl-cyclase-dependent pathways modulate
      reorganization of the actin cytoskeleton to form structures that facilitate
      adhesion. In contrast, little is known about participation of Rho proteins and
      Rho signaling in actin rearrangements. We report here the in vivo expression of
      at least one Rho protein in trophozoites, whose activation induced actin
      reorganization and actin-myosin interaction. Antibodies to EhRhoA1 recombinant
      protein mainly localized Rho in the cytosol of nonactivated amoebae, but it was
      translocated to vesicular membranes and to some extent to the plasma membrane
      after treatment with lysophosphatidic acid (LPA), a specific agonist of Rho
      activation. Activated Rho was identified in LPA-treated trophozoites. LPA induced
      striking polymerization of actin into distinct dynamic structures.
      Disorganization of these structures by inhibition of Rho effector, Rho-kinase
      (ROCK), and by ML-7, an inhibitor of myosin light chain kinase dependent
      phosphorylation of myosin light chain, suggested that the actin structures also
      contained myosin. LPA stimulated concanavalin-A-mediated formation of caps,
      chemotaxis, invasion of extracellular matrix substrates, and erythrophagocytosis,
      but not binding to fibronectin. ROCK inhibition impaired LPA-stimulated functions
      and to some extent adhesion to fibronectin. Similar results were obtained with ML
      7. These data suggest the presence and operation of Rho-signaling pathways in E.
      histolytica, that together with other, already described, signaling routes
      modulate actomyosin-dependent motile processes, particularly stimulated during
      invasive behavior.

PMID- 16421928
TI  - Self-organized and highly ordered domain structures within swarms of Myxococcus
      xanthus.
AB  - Coordinated group movement (swarming) is a key aspect of Myxococcus xanthus'
      social behavior. Here we report observation of domain structures formed by
      multiple cells within large three-dimensional swarming groups grown on amorphous
      glass substrates, using the atomic force microscope (AFM). Novel analyses
      revealed that 90% of the wild type swarms displayed some form of preferential
      cell alignment. In contrast, cells with mutations in the social and adventurous
      motility systems displayed a distinct lack of cell alignment. Video microscopy
      observations of domain features of in vivo swarming M. xanthus cells were also
      consistent with the AFM data. The results presented here reveal that unique
      domain formation within swarms of wild type cells is a biologically driven
      process requiring the social and adventurous motility systems and is not a
      statistical phenomenon or thermodynamic process arising from liquid crystal
      behavior.

PMID- 16421929
TI  - Steady-state and time-resolved fluorescence studies of the intestinal fatty acid
      binding protein.
AB  - The intestinal fatty acid binding protein contains two tryptophan residues (Trp6
      and Trp82) both of which have been shown by X-ray and NMR methods to be buried in
      hydrophobic clusters. By using a combination of steady-state and time-resolved
      fluorescence experiments, we have deconvoluted the lifetime weighted contribution
      of each of the tryptophans to the steady-state fluorescence quantum yield. While
      Trp82 has been implicated in an intermediate that appears at relatively high
      denaturant concentrations, the variation of the lifetime weighted contribution of
      Trp6 with urea or guanidium hydrochloride shows formation of an intermediate
      state at low concentrations of the denaturant before the actual unfolding starts.
      Trp82 did not show similar behavior. Fluorescence quenching experiments by
      acrylamide show that while Trp6 in the native protein is less solvent-exposed,
      its accessibility is increased significantly at low urea concentration indicating
      that the early intermediate state is partially unfolded. Time-resolved anisotropy
      experiments indicate that the volume of the partially unfolded intermediates is
      larger than the native protein and lead to the speculation that the last step of
      the protein folding might be the removal of solvent molecules from the protein.

PMID- 16421930
TI  - Crystal structure at 1.45-A resolution of the major allergen endo-beta-1,3
      glucanase of banana as a molecular basis for the latex-fruit syndrome.
AB  - Resolution of the crystal structure of the banana fruit endo-beta-1,3-glucanase
      by synchrotron X-ray diffraction at 1.45-A resolution revealed that the enzyme
      possesses the eightfold beta/alpha architecture typical for family 17 glycoside
      hydrolases. The electronegatively charged catalytic central cleft harbors the two
      glutamate residues (Glu94 and Glu236) acting as hydrogen donor and nucleophile
      residue, respectively. Modeling using a beta-1,3 linked glucan trisaccharide as a
      substrate confirmed that the enzyme readily accommodates a beta-1,3-glycosidic
      linkage in the slightly curved catalytic groove between the glucose units in
      positions -2 and -1 because of the particular orientation of residue Tyr33
      delimiting subsite -2. The location of Phe177 in the proximity of subsite +1
      suggested that the banana glucanase might also cleave beta-1,6-branched glucans.
      Enzymatic assays using pustulan as a substrate demonstrated that the banana
      glucanase can also cleave beta-1,6-glucans as was predicted from docking
      experiments. Similar to many other plant endo-beta-1,3-glucanases, the banana
      glucanase exhibits allergenic properties because of the occurrence of well
      conserved IgE-binding epitopes on the surface of the enzyme. These epitopes might
      trigger some cross-reactions toward IgE antibodies and thus account for the IgE
      binding cross-reactivity frequently reported in patients with the latex-fruit
      syndrome.

PMID- 16421931
TI  - Bladder cancer risk in sales workers: artefact or cause for concern?
AB  - BACKGROUND: A large number of epidemiological studies have reported positive
      associations between bladder cancer and sales occupations. We investigated
      whether these findings are likely to be due to chance, confounding or publication
      bias, or may involve causal associations. METHODS: Studies reporting bladder
      cancer risk-estimates for sales occupations were reviewed. Using meta-analyses we
      assessed heterogeneity and publication bias, and derived summary estimates.
      RESULTS: Eighteen publications were identified, reporting 85 risk-estimates for
      sales-work. Meta-estimates were elevated for men (odds ratio (OR) 1.11, 95%
      confidence interval (CI) 1.01-1.21) and women (OR = 1.36, 95% CI = 1.11-1.67).
      The estimate was heterogeneous for men (p(Q-test) <0.01, women: 0.18) and
      indicated publication bias for women (p(Egger-test) <0.01, men: 0.40). When
      including only smoking-adjusted estimates reported irrespective of the strength
      of the association, the summary estimate for generic groups of sales workers was
      0.99 (95% CI 0.90-1.08) for men, and 1.18 (95% CI = 0.99-1.39) for women, without
      statistically significant heterogeneity or publication bias. For women, risk was
      positively associated with longer duration of sales-employment in three studies.
      CONCLUSIONS: Publication bias explained most of the reported increased bladder
      cancer risk, but sales-work still appeared to be associated with a small risk in
      women. Possible causal factors include lower frequency of urination and reduced
      fluid intake.

PMID- 16421933
TI  - The proteomic analysis of an adipocyte differentiated from human mesenchymal stem
      cells using two-dimensional gel electrophoresis.
AB  - Adipose tissues play a crucial endocrine role in the control of whole body
      glucose homeostasis and insulin sensitivity. Considering the current substantial
      rise in obesity and obesity-related diseases, including diabetes, it is important
      to understand the molecular basis of adipocyte differentiation and its control.
      In this study, we have analyzed the protein expression inherent to adipogenic
      differentiation, by 2-DE, MALDI-TOF, and RT-PCR. This study focused on proteins
      that were differentially expressed by the differentiation of human mesenchymal
      stem cells (hMSCs) to adipocytes. We conducted 2-DE for each set of proteins in
      the cytosol of adipocytes that had differentiated from hMSC, in a pH range from 3
      10. Thirty-two protein spots were shown to have different expression levels.
      Among these, eight up-regulated proteins were identified by MALDI-TOF/MS, as the
      following: syntaxin binding protein 3, OSBP-related protein 3, phosphodiesterase,
      glycophorin, immunoglobulin kappa chain variable region, peroxisome proliferative
      activated receptor gamma (PPAR-gamma), bA528A10.3.1 (novel protein similar to
      KIAA01616, isoform 1), and T cell receptor V-beta 4. Four proteins: syntaxin-3,
      OSBP-related protein 3, PPAR-gamma and glycophorin were associated with
      adipogenesis.

PMID- 16421932
TI  - Runx2 phosphorylation induced by fibroblast growth factor-2/protein kinase C
      pathways.
AB  - Runx2 is a key transcription factor in osteoblast differentiation, and its
      activity is regulated by fibroblast growth factors (FGFs). Craniosynostosis,
      characterized by premature suture closure, results from mutations that generate
      constitutively active FGF receptors (FGFRs). We previously showed that FGF/FGFR
      activated protein kinase C (PKC) is involved in the expression and activity of
      Runx2. Activated PKCdelta physically interacts with Runx2 in FGF2-stimulated
      MC3T3-E1 preosteoblastic cells. Immunopurified Runx2 protein reacted with
      PKCdelta kinase, and a phosphorylated 1460-Da peptide fragment (amino acids 241
      252, 1380-Da) derived from Runx2 was also detected in MS analysis. Computer
      analysis predicted that Ser247 in this Runx2 can be a possible phosphorylation
      site by PKCdelta. We also showed that Runx2 activity after FGF stimulation
      correlates with the presence of the Runx2 Ser247 residue. The S247A (Ser --> Ala)
      mutation confers decreased transcriptional activity on a Runx2-responsive
      promoter after FGF treatment.

PMID- 16421934
TI  - Proteomic analysis of pathogenic bacterium Vibrio vulnificus.
AB  - In this study we have constructed a proteome reference map of the pathogenic
      bacterium Vibrio vulnificus. From the reference map, we identified several
      virulence-related proteins, such as ToxR and ToxS, as well as numerous proteins
      involved in diverse cellular functions. To search for additional virulence
      related proteins, we compared the whole proteomes from the wild-type and toxR
      mutant of V. vulnificus and found that several proteins were up- or down
      regulated in the toxR mutant. We suggest that these differentially regulated
      proteins whose expression is coordinately controlled by a virulence regulator
      ToxR, some of which are already implicated in virulence, play roles in the
      pathogenesis of V. vulnificus.

PMID- 16421935
TI  - Characterization of plasma gelsolin as a substrate for matrix metalloproteinases.
AB  - We previously showed that plasma gelsolin, a major component of the extracellular
      actin scavenging system, is an matrix metalloproteinase (MMP)-14 substrate. Here
      we confirmed that plasma gelsolin is cleaved by MMP-14 at the plasma level, and
      found that it was most efficiently digested by MMP-3 followed by MMP-2, MMP-1,
      MMP-14, and MMP-9, in that order. Plasma gelsolin (90 kDa) was cut into several
      fragments of 43-48 kDa by MMP-3. The MMP-3 cleavage sites in plasma gelsolin were
      determined by labeling the C termini generated by in-gel digestion with 50% H2
      18O combined with peptide mass mapping, and sequencing of the N-terminal amino
      acids. Plasma gelsolin was cleaved at Asn416-Val417, Ser51-Met52, and Ala435
      Gln436. Proteolytic cleavage by MMP-3 resulted in considerable loss of its actin
      filament-depolymerizing activity. This suggests that MMPs weaken the
      extracellular actin-scavenging system by cleaving plasma gelsolin and may,
      therefore, be involved in pathological conditions induced by extracellular actin,
      such as endothelial injury, respiratory distress syndrome, hepatic necrosis, and
      septic shock.

PMID- 16421936
TI  - Proteomic analysis of heterotrophy in Synechocystis sp. PCC 6803.
AB  - To provide an insight into the heterotrophic metabolism of cyanobacteria, a
      proteomic approach has been employed with the model organism Synechocystis sp.
      PCC 6803. The soluble proteins from Synechocystis grown under photoautotrophic
      and light-activated heterotrophic conditions were separated by 2-DE and
      identified by MALDI-MS or LC-MS/MS analysis. 2-DE gels made using narrow- and
      micro-range IPG strips allowed quantitative comparison of more than 900 spots.
      Out of 67 abundant protein spots identified, 13 spots were increased and 9
      decreased under heterotrophy, representing all the major fold changes. Proteomic
      alterations and activity levels of selected enzymes indicate a shift in the
      central carbon metabolism in response to trophic change. The significant
      reduction in light-saturated rate of photosynthesis as well as in the expression
      levels of rubisco and CO(2)-concentrating mechanism proteins under heterotrophy
      indicates the down-regulation of the photosynthetic machinery. Alterations in the
      expression level of proteins involved in carbon utilization pathways refer to
      enhanced glycolysis, oxidative pentose phosphate pathway as well as tricarboxylic
      acid cycle under heterotrophy. Proteomic evidences also suggest an enhanced
      biosynthesis of amino acids such as histidine and serine during heterotrophic
      growth.

PMID- 16421937
TI  - Identification of an anti-aldolase autoantibody as a diagnostic marker for
      diabetic retinopathy by immunoproteomic analysis.
AB  - Circulating autoantibodies specific for retinal proteins are associated with
      retinal destruction in patients with diabetic retinopathy (DR). In this study, we
      screened diabetic sera for the presence of anti-retinal autoantibodies with an
      aim of developing diagnostic markers for DR. Immunoblot analysis of DR patients'
      sera with human retinal cytosolic proteins revealed a higher incidence of anti
      retinal autoantibodies, compared to normal blood donors or diabetic patients
      without DR. Anti-retinal protein autoantibody profiles of DR patient sera were
      obtained by 2-DE immunoblot analysis. Specifically, 20 protein spots reactive
      with DR patient sera were identified by ESI-MS/MS. Of these spots, 14 were
      specific for DR patients, and 4 reacted with both non-proliferative DR (non-PDR)
      and PDR sera. The anti-aldolase autoantibody was selected as a DR marker
      candidate, and specific reactivity of DR patient sera was confirmed by immunoblot
      analysis with rabbit aldolase. The serum anti-aldolase autoantibody level was
      measured by ELISA. DR patients showed significantly higher autoantibody levels
      than normal donors or diabetic patients without retinopathy. However, no
      significant differences were observed between non-PDR and PDR patients,
      suggesting that the level of anti-aldolase autoantibody is not determined by the
      severity of retinopathy in diabetic patients. Our data collectively demonstrate
      that the anti-aldolase autoantibody serves as a useful marker for DR diagnosis.

PMID- 16421938
TI  - The cassava (Manihot esculenta Crantz) root proteome: protein identification and
      differential expression.
AB  - Using high-resolution 2-DE, we resolved proteins extracted from fibrous and
      tuberous root tissues of 3-month-old cassava plants. Gel image analysis revealed
      an average of 1467 electrophoretically resolved spots on the fibrous gels and
      1595 spots on the tuberous gels in pH 3-10 range. Protein spots from both sets of
      gels were digested with trypsin. The digests were subjected to nanoelectrospray
      quadrupole TOF tandem mass analysis. Currently, we have obtained 299 protein
      identifications for 292 gel spots corresponding to 237 proteins. The proteins
      span various functional categories from energy, primary and secondary metabolism,
      disease and defense, destination and storage, transport, signal transduction,
      protein synthesis, cell structure, and transcription to cell growth and division.
      Gel image analysis has shown unique, as well as up- and down-regulated proteins,
      present in the tuberous and the fibrous tissues. Quantitative and qualitative
      analysis of the cassava root proteome is an important step towards further
      characterization of differentially expressed proteins and the elucidation of the
      mechanisms underlying the development and biological functions of the two types
      of roots.

PMID- 16421939
TI  - An observation of unusual temperature effects for enantioselective CZE employing
      highly sulfated-beta-cyclodextrin.
AB  - In this paper data are presented suggesting that for enantiomers of basic and
      neutral analytes, the concentrations of highly sulfated CDs typically used are
      above the optimum since lower concentrations result in unacceptable migration
      times. This situation arises because of the high binding affinities often
      obtained with sulphated CDs. In a system being over the optimum CD concentration
      increasing the temperature of the capillary offers a capability to improve
      selectivity and reduce migration times.

PMID- 16421940
TI  - Mechanism of enantioseparation of DL-pantothenic acid in ligand exchange
      capillary electrophoresis using a diol-borate system.
AB  - Borate complexes formed in the ternary system at pH 9.2 containing borate, (S)-3
      amino-1,2-propanediol (SAP), and DL-pantothenic acid (DL-PTA) were identified by
      13C and 11B NMR, and it is confirmed that the binary complexes, [B(OH)2(SAP)],
      [B(SAP)2]+ [B(OH)2(D- or L-PTA)]2-, and [B(D- or L-PTA)2]3- (including [B(D
      PTA)(L-PTA)]3-), and the ternary complexes, [B(SAP)(D- or L-PTA)]-, coexist at
      equilibrium in the ternary system. Thermodynamic experiments by variable
      temperature 11B NMR revealed that the ternary complex, [B(SAP)(D-PTA)]-, is
      entropically more stable than [B(SAP)(L-PTA)]-. Because two geometrical isomers
      are possible for the respective ternary complexes, semi-empirical molecular
      orbital calculations were performed by PM5, PM3, and AM1 methods in order to
      obtain the optimized structures. It is indicated from the calculated heats of
      formation and experimentally obtained thermodynamic parameters that the (S)
      isomer is more probable for the respective ternary complexes with D- and L-PTA.
      In the optimized structure of (S)-[B(SAP)(D-PTA)]- in water, the SAP and D-PTA
      ligands were oppositely oriented to form a rather linear structure, while the
      diastereomer, (S)-[B(SAP)(L-PTA)]-, had a folded structure. Because such a
      difference in the solvated structure of the ternary complexes can give a
      different electrophoretic velocity in CE, the enantioseparation of DL-PTA in CE
      is reasonably attributed to a difference in the observed electrophoretic mobility
      for the equilibrated ternary systems containing the respective ternary complexes.

PMID- 16421941
TI  - Enhanced binding and conformational selectivity in affinity capillary
      electrophoresis using a water-soluble resorcin[4]arene as intrinsic buffer and
      electrokinetic host.
AB  - Affinity capillary electrophoresis (ACE) is a widely used technique for
      quantifying non-covalent molecular interactions that is dependent on the specific
      buffer conditions selected. In this study, dynamic 1:1 host-guest inclusion
      complexation involving a charged resorcin[4]arene with a group of neutral
      corticosteroids was examined by ACE, where the macrocycle serves as both an
      intrinsic buffer and electrokinetic host. It was determined that over a 200%
      enhancement in the apparent binding constant (KB) was realized by ACE when using
      the host as an intrinsic buffer at pH 7.5 relative to an extrinsic sodium
      phosphate buffer system, which was also confirmed by 1H-NMR experiments. This
      report also revealed improved selectivity mediated by the discrete conformational
      properties of the complex among similar corticosteroid guests, as reflected by
      the complex mobility (mu(ep, AC)) or the relative change in complexation-induced
      mobility (1-mu(ep, AC)/mu(ep, C)). This latter property is a unique feature of
      ACE reflective of hydrodynamic size selectivity involving bulky guests or
      substrates. 1H-NMR and computer molecular modeling provided complementary
      information regarding the relative orientation, conformation and overall
      molecular area of the complex. The coupling of thermodynamic (KB) and
      electrokinetic (mu(ep, AC)) factors associated with complex formation in buffered
      solutions that minimize the effects of extrinsic electrolytes serves to enhance
      enthalpy-driven molecular recognition processes by ACE.

PMID- 16421943
TI  - Large-pore mesoporous SBA-15 silica particles with submicrometer size as
      stationary phases for high-speed CEC separation.
AB  - A new mesoporous sphere-like SBA-15 silica was synthesized and evaluated in terms
      of its suitability as stationary phases for CEC. The unique and attractive
      properties of the silica particle are its submicrometer particle size of 400 nm
      and highly ordered cylindrical mesopores with uniform pore size of 12 nm running
      along the same direction. The bare silica particles with submicrometer size have
      been successfully employed for the normal-phase electrochromatographic separation
      of polar compounds with high efficiency (e.g., 210,000 for thiourea), which is
      matched well with its submicrometer particle size. The Van Deemeter plot showed
      the hindrance to mass transfer because of the existence of pore structure. The
      lowest plate height of 2.0 microm was obtained at the linear velocity of 1.1
      mm/s. On the other hand, because of the relatively high linear velocity (e.g.,
      4.0 mm/s) can be generated, high-speed separation of neutral compounds, anilines,
      and basic pharmaceuticals in CEC with C18-modified SBA-15 silica as stationary
      phases was achieved within 36, 60, and 34 s, respectively.

PMID- 16421942
TI  - Effects of G-quartet DNA stationary phase destabilization on fibrinogen peptide
      resolution in capillary electrochromatography.
AB  - The migration of fibrinogen peptides in capillaries coated with G-quartet-forming
      DNA oligonucleotides in open-tubular CEC (OTCEC) was studied, in order to
      investigate factors affecting the retention of peptides on G-quartet DNA
      stationary phases. At 25 degrees C, the peptides eluted in the same order in
      OTCEC using a two-plane G-quartet DNA stationary phase as in CZE, including two
      peptides that were completely overlapped. It was found that baseline resolution
      of the coeluting peptides could be achieved in the OTCEC experiment, but not in
      CZE, at run temperatures of 35-40 degrees C. A stationary phase formed by a
      scrambled-sequence oligonucleotide that does not form a G-quartet did not provide
      any resolution of the two coeluting peptides, even at the higher temperatures,
      indicating that some destabilization of the G-quartet enhances resolution but
      that some degree of G-quartet structure is necessary. The effects of
      destabilization were further explored through variation of the cations (sodium or
      potassium) used in attachment of the G-quartet oligonucleotide to the capillary
      surface and in the mobile-phase buffer. Resolution was lower when a more stable,
      four-plane G-quartet stationary phase was used, supporting the conclusion that
      some flexibility in the G-quartet structure facilitates differential interactions
      that resolve otherwise coeluting peptides. The increase in peptide resolution
      upon destabilization of the G-quartet structure could prove to be an important
      factor in the application of G-quartet DNA stationary phases for nonaffinity
      based separation of native proteins and peptides.

PMID- 16421944
TI  - Binding of human serum amyloid P componentto L-selectin.
AB  - Serum concentrations of soluble L-selectin by far exceed those of other soluble
      adhesion molecules, and serum soluble L-selectin concentrations are remarkably
      stable upon prolonged storage. We present evidence for Ca(2+)-dependent binding
      interactions between human serum amyloid P (SAP), a proteolysis-resistant
      pentraxin glycoprotein, and L-selectin, as shown by surface plasmon resonance
      measurements, protein band shift assays in a native PAGE system, and after SDS
      PAGE and membrane transfer. Monoclonal antibodies to L-selectin strongly reduced
      binding of biotinylated SAP to L-selectin-IgG chimeras immobilized on microtiter
      plates. As binding was reduced by prior glycopeptidase F treatment of L-selectin
      but not of SAP, it appears to be based on SAP lectin domain interactions with N
      linked L-selectin carbohydrates. In freshly prepared human lymphocytes, SAP
      incubation induced expression of a beta2 integrin neoepitope associated with high
      affinity binding. This was partially blocked by pre-incubation with Fab fragments
      of two anti-L-selectin antibodies. In flow chamber experiments, SAP inhibited the
      adherence of human neutrophils to activated endothelium under shear stress. Thus,
      SAP binds to human L-selectin and affects L-selectin-dependent leukocyte
      endothelial interactions.

PMID- 16421945
TI  - Migration of cytotoxic T lymphocytes toward melanoma cells in three-dimensional
      organotypic culture is dependent on CCL2 and CCR4.
AB  - Studies in experimental animal models have demonstrated that chemokines produced
      by tumor cells attract chemokine receptor-positive T lymphocytes into the tumor
      area. However, in cancer patients, the role of chemokines in T lymphocyte
      trafficking toward human tumor cells is relatively unexplored. In the present
      study, the migration of a melanoma patient's CTL toward autologous tumor cells
      has been studied in a novel three-dimensional organotypic melanoma culture. In
      this model, CTL migrated toward tumor cells, resulting in tumor cell apoptosis.
      CTL migration was mediated by the CC chemokine receptor (CCR)4 expressed by the
      CTL and the CC chemokine ligand (CCL)2 secreted by the tumor cells, as evidenced
      by blockage of CTL migration by CCL2 or antibodies to CCL2 or CCR4. These results
      were confirmed in a Transwell migration assay in which the CTL actively migrated
      toward isolated CCL2 and migration was inhibited by anti-CCR4 antibody. These
      studies, together with previous studies in mice indicating regression of CCL2
      transduced tumor cells, suggest that CCL2 may be useful as an immunotherapeutic
      agent for cancer patients.

PMID- 16421946
TI  - IL-7Ralpha expression on CD4+ T lymphocytes decreases with HIV disease
      progression and inversely correlates with immune activation.
AB  - Many factors can influence the rate of HIV disease progression, including those
      that maintain T cell homeostasis. One key homeostatic regulator is the IL-7
      receptor (IL-7R). Previous studies have shown IL-7R expression levels decrease in
      HIV infection, but effects on memory subtypes, CD4(+) T cells, and cell function
      have not been explored. The present study examined the expression of the IL
      7Ralpha chain on naive and memory T lymphocyte subsets of both HIV-positive and
      HIV-negative individuals from Nairobi, Kenya to assess the role of IL-7Ralpha in
      HIV disease. Expression of IL-7Ralpha was significantly reduced in all CD4(+) and
      CD8(+) T cell subsets in HIV-positive individuals. This reduction was further
      enhanced in those with advanced HIV progression. Expression of IL-7Ralpha was
      inversely correlated to immune activation, and apoptosis, and was positively
      correlated with CD4 count in both bivariate and multivariate analysis. Expression
      of IL-7Ralpha did not correlate with HIV viral loads, indicating the elevated
      immune activation seen in HIV-infected individuals may be impacting expression of
      IL-7Ralpha, independent of viral loads. Signaling via the IL-7R is essential for
      T cell homeostasis and maintenance of T cell memory. Reduction of this receptor
      may contribute to the homeostatic disruption seen in HIV.

PMID- 16421947
TI  - Macrophage and T lymphocyte apoptosis during experimental pulmonary tuberculosis:
      their relationship to mycobacterial virulence.
AB  - The kinetics of macrophage and T lymphocyte apoptosis were determined in a well
      characterized mouse model of pulmonary tuberculosis, comparing strains of
      intermediate (H37Rv) and high virulence (Beijing strain, code 9501000). Both
      strains induced a high percentage of apoptotic activated macrophages at days 1
      and 3 post infection, although this was twofold lower in Beijing-infected mice.
      Progressive pneumonia started at day 14 (Beijing) or 21 (H37Rv) post infection.
      Pneumonic areas contained numerous macrophages with vacuolated cytoplasm (VM). In
      H37Rv infection few VM were apoptotic (8.7% at day 60), and the percentage was
      even lower in Beijing infection (1.4% at day 28). A high percentage of VM
      expressed the anti-apoptotic molecule Bcl-2 (H37Rv, 83%; Beijing, 95%). Both
      strains induced a progressive increase of apoptotic Th1 lymphocytes, peaking at
      day 60 in H37Rv infection, or 28 in Beijing infection. The peak was twofold
      higher in the latter. VM had strong FasL immunostaining, and confocal microscopy
      showed numerous apoptotic Th1 cells closely associated with them, suggesting that
      VM might induce apoptosis of Th1 cells. These results support the hypothesis that
      apoptosis of macrophages is associated with protection, while apoptosis of Th1
      cells favors disease progression, and is related to the virulence of the
      mycobacterial strain.

PMID- 16421948
TI  - CpG motif-independent activation of TLR9 upon endosomal translocation of
      "natural" phosphodiester DNA.
AB  - Endosomally translocated host (self) DNA activates Toll-like receptor 9 (TLR9),
      while extracellular self-DNA does not. This inconsistency reflects poor endosomal
      DNA translocation but also implies that host DNA contains DNA sequences that
      function as ligands for TLR9. Herein we report that contrary to phosphorothioate
      (PS)-stabilized oligonucleotides (ODN), "natural" phosphodiester (PD) ODN lacking
      CpG motifs activate TLR9. CpG motif-independent TLR9 activation of Flt3-L-induced
      dendritic cells (DC) was dependent on enforced endosomal translocation and
      triggered upregulation of CD40 and CD69 as well as production of IL-6 and IFN
      alpha. Binding studies utilizing surface plasmon resonance technology (Biacore)
      revealed low TLR9 binding to single-stranded (ss) PD-ODN lacking CpG motifs. At
      higher concentrations their TLR9 binding activity compared well with TLR9 binding
      of canonical ss PD CpG-ODN. These results imply that both the chemical
      modification of the DNA backbone as well as the amount of endosomally
      translocated DNA represent determining factors that allow CpG motif-independent
      activation of TLR9 by ss PD-DNA.

PMID- 16421949
TI  - Increased antigen presenting cell-mediated T cell activation in mice and patients
      without the autoimmune regulator.
AB  - Patients with autoimmune polyendocrine syndrome type I (APS I)suffer from
      endocrine and non-endocrine disorders due to mutations in the autoimmune
      regulator gene (AIRE). Mouse Aire is expressed both in thymic medullary
      epithelial cells and in peripheral antigen-presenting cells, suggesting a role in
      both central and peripheral tolerance. We here report that Aire(-/-) dendritic
      cells (DC) activate naive T cells more efficiently than do Aire(+/+) DC.
      Expression array analyses of Aire(-/-) DC revealed differential regulation of 68
      transcripts, among which, the vascular cell adhesion molecule-1 (VCAM-1)
      transcript was up-regulated in Aire(-/-) DC. Concurrently, the expression of the
      VCAM-1 protein was up-regulated on both Aire(-/-) DC and monocytes from APS I
      patients. Blocking the interaction of VCAM-1 prevented enhanced Aire(-/-) DC
      stimulation of T cell hybridomas. We determined an increased number of DC in
      spleen and lymph nodes and of monocytes in the blood from Aire(-/-) mice, and an
      increased number of blood monocytes in APS I patients. Our findings imply a role
      for Aire in peripheral DC regulation of T cell activation, and suggest that Aire
      participates in peripheral tolerance.

PMID- 16421951
TI  - Sensitive chiral analysis by capillary electrophoresis.
AB  - In this review, an updated view of the different strategies used up to now to
      enhance the sensitivity of detection in chiral analysis by CE will be provided to
      the readers. With this aim, it will include a brief description of the
      fundamentals and most of the recent applications performed in sensitive chiral
      analysis by CE using offline and online sample treatment techniques (SPE, liquid
      liquid extraction, microdialysis, etc.), on-column preconcentration techniques
      based on electrophoretic principles (ITP, stacking, and sweeping), and
      alternative detection systems (spectroscopic, spectrometric, and electrochemical)
      to the widely used UV-Vis absorption detection.

PMID- 16421950
TI  - Recent advances in amino acid analysis by capillary electrophoresis.
AB  - This paper describes a number of articles that have been published on amino acid
      analysis using CE during the period from June 2003 to May 2005. This review
      article follows the previous ones of Smith (Electrophoresis 1999, 20, 3078-3083),
      Prata et al. (Electrophoresis 2001, 22, 4129-4138), and Poinsot et al.
      (Electrophoresis 2003, 24, 4047-4062). Several new developments in amino acid
      analysis with CE are reported concerning UV detection, LIF, MS, and NMR. In
      addition, we describe articles concerning clinical and pharmaceutical studies,
      neuroclinical applications, and agricultural and food analysis.

PMID- 16421952
TI  - Advances in the enantioseparation of second-generation antidepressant drugs by
      electrodriven methods.
AB  - Stereochemistry is steadily increasing in importance in the development of new
      drugs, and the availability of pure enantiomer drugs can make therapy safer and
      more efficacious. In particular, almost all second-generation antidepressant
      drugs possess one or more chiral centres; however, only some of them are
      administered as single enantiomers. A fundamental part of the quality control of
      pharmaceutical formulations is the determination of enantiomeric excess and
      enantiomeric purity; this is also important for the therapeutic drug monitoring
      of depressed patients. For this purpose, efficient and reliable analytical
      methods are needed and electrodriven techniques (most of all CE, CEC and MEKC)
      are very efficient and inexpensive candidates for the role. In this review, the
      enantioselective electrodriven methods available for the analysis of second
      generation antidepressant are presented and discussed. In particular, the
      following pharmacological classes of antidepressants will be considered:
      selective serotonin reuptake inhibitors (fluoxetine, citalopram, paroxetine,
      sertraline); norepinephrine reuptake inhibitors (reboxetine); serotonin and
      norepinephrine reuptake inhibitors (venlafaxine, milnacipran, duloxetine); and
      noradrenergic and specific serotonergic antidepressants (mirtazapine).

PMID- 16421953
TI  - Recent advances in the applications of CE to forensic sciences (2001-2004).
AB  - The present article reviews the applications of CE in forensic science covering
      the period from 2001 until the first part of 2005. The overview includes the most
      relevant examples of analytical applications of capillary electrophoretic and
      electrokinetic techniques in the following fields: (i) Forensic drugs and
      poisons, (ii) explosive analysis and gunshot residues, (iii) small ions of
      forensic interest, (iv) forensic DNA and RNA analysis, (v) proteins of forensic
      interest, and (vi) ink analysis.

PMID- 16421954
TI  - Recent advances in the analysis of antibiotics by capillary electrophoresis.
AB  - In this review, the main aspects related to the separation of different groups of
      antibiotics by CE as well as the different applications reported in the
      literature from the beginning 2003 till May 2005 will be provided to the readers.
      Firstly, the experimental conditions employed to achieve the analysis of
      antibiotics by CE are given. Then, the main applications performed in the
      pharmaceutical, clinical, food, and environmental fields have been reviewed
      making emphasis on sample preparation requirements needed in each case. Finally,
      the main conclusions and future prospects in this field are presented.

PMID- 16421955
TI  - Recent advances of transient isotachophoresis-capillary electrophoresis in the
      analysis of small ions from high-conductivity matrices.
AB  - Since its invasion into the field of small ion analysis, quantitation of trace
      ionic analytes has always been a challenging task for CE, especially when dealing
      with highly saline samples. This review summarizes the method's progress and
      significant developments in the area due to its combination with on-line
      preconcentration by transient ITP (tITP). Principles of tITP stacking in high
      conductivity solutions and operational preconcentration modes are considered. The
      most important application areas covered in this review include the analysis of
      seawater and biological fluids (urine, serum, etc.). Examples cited in this
      review demonstrate that tITP-CE is now on a certain way of becoming a recognized
      technique when the determination of trace ionic species in loaded matrices is the
      aim.

PMID- 16421959
TI  - Capillary electrophoresis at the omics level: towards systems biology.
AB  - Emerging systems biology aims at integrating the enormous amount of existing
      omics data in order to better understand their functional relationships at a
      whole systems level. These huge datasets can be obtained through advances in high
      throughput, sensitive, precise, and accurate analytical instrumentation and
      technological innovation. Separation sciences play an important role in revealing
      biological processes at various omic levels. From the perspective of systems
      biology, CE is a strong candidate for high-throughput, sensitive data generation
      which is capable of tackling the challenges in acquiring qualitative and
      quantitative knowledge through a system-level study. This review focuses on the
      applicability of CE to systems-based analytical data at the genomic,
      transcriptomic, proteomic, and metabolomic levels.

PMID- 16421961
TI  - Chemiluminescence enzyme immunoassay (CLEIA) for the determination of
      chloramphenicol residues in aquatic tissues.
AB  - A competitive indirect chemiluminescence enzyme immunoassay (ic-CLEIA) for
      chloramphenicol (CAP) residues in shrimp has been developed. After optimization
      (incubation time, concentration of Tween-20, concentration of PBS and pH), the
      method gave a limit of detection of 0.01 ng/mL and a detection range of 0.03-23.7
      ng/mL, with an ED(50) of 0.47 ng/mL. The method has been validated on spiked
      shrimp samples in terms of precision (intra- and interassay coefficient
      variations of less than 10% and 15%, respectively) and accuracy (mean recovery 95
      123%). The assay performance is better than the ELISA method which is widely used
      to detect chloramphenicol and indicates that the CLEIA method can be used to test
      aquatic samples instead of ELISA.

PMID- 16421962
TI  - Crystallization inhibition of an amorphous sucrose system using raffinose.
AB  - The shelf life of pure amorphous sucrose systems, such as cotton candy, can be
      very short. Previous studies have shown that amorphous sucrose systems held above
      the glass transition temperature will collapse and crystallize. One study,
      however, showed that adding a small percent of another type of sugar, such as
      trehalose, to sucrose can extend the shelf life of the amorphous system by
      slowing crystallization. This study explores the hypothesis that raffinose
      increases the stability of an amorphous sucrose system. Cotton candy at 5 wt%
      raffinose and 95 wt% sucrose was made and stored at room temperature and three
      different relative humidities (%RH) 11%RH, 33%RH, and 43%RH. XRD patterns, and
      glass transition temperatures were obtained to determine the stability as a
      function of %RH. The data collected showed that raffinose slows sucrose
      crystallization in a low moisture amorphous state above the glass transition
      temperature and therefore improves the stability of amorphous sucrose systems.

PMID- 16421963
TI  - Nutritional evaluation of caseins and whey proteins and their hydrolysates from
      Protamex.
AB  - Whey protein concentrate (WPC 80) and sodium caseinate were hydrolyzed by
      Protamex to 5%, 10%, 15%, and 20% degree of hydrolysis (DH). WPC 80, sodium
      caseinate and their hydrolysates were then analyzed, compared and evaluated for
      their nutritional qualities. Their chemical composition, protein solubility,
      amino acid composition, essential amino acid index (EAA index), biological value
      (BV), nutritional index (NI), chemical score, enzymic protein efficiency ratio (E
      PER) and in vitro protein digestibility (IVPD) were determined. The results
      indicated that the enzymatic hydrolysis of WPC 80 and sodium caseinate by
      Protamex improved the solubility and IVPD of their hydrolysates. WPC 80, sodium
      caseinate and their hydrolysates were high-quality proteins and had a surplus of
      essential amino acids compared with the FAO/WHO/UNU (1985) reference standard.
      The nutritive value of WPC 80 and its hydrolysates was superior to that of sodium
      caseinate and its hydrolysates as indicated by some nutritional parameters such
      as the amino acid composition, chemical score, EAA index and predicted BV.
      However, the E-PER was lower for the WPC hydrolysates as compared to unhydrolyzed
      WPC 80 but sodium caseinate and its hydrolysates did not differ significantly.
      The nutritional qualities of WPC 80, sodium caseinate and their hydrolysates were
      good and make them appropriate for food formulations or as nutritional
      supplements.

PMID- 16421964
TI  - Early metabolism evaluation making traditional Chinese medicine effective and
      safe therapeutics.
AB  - Increasing attention is being paid to the scientific evaluation of traditional
      Chinese medicine (TCM). As many TCMs are capable of biotransformation in the
      gastrointestinal tract, attention to biotransformation of TCM in the
      gastrointestinal tract may lead to discovery of the active components and active
      mechanisms. In this article, we review reports that host metabolic enzymes and
      intestinal bacteria may be responsible for the metabolism of TCM. Good
      understanding of the in vivo course of TCM will help us to know how to conduct
      metabolism evaluation of TCM by using in vitro human-derived system. This
      evaluation system will create new views on TCM as effective and safe therapeutic
      agents.

PMID- 16421965
TI  - Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens
      during three phases of morphine induced conditioned place preference in rats.
AB  - OBJECTIVE: To investigate the changes in CREB (cAMP response element binding
      protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens)
      during three phases of morphine induced CPP (conditioned place preference) in
      rats, and to elucidate the role of CREB during the progress of conditioned place
      preference. METHODS: Morphine induced CPP acquisition, extinction and drug primed
      reinstatement model was established, and CREB expression in each brain area was
      measured by Western Blot methods. RESULTS: Eight alternating injections of
      morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that
      extinguished CPP. CPP was reinstated following a priming injection of morphine
      (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of
      CREB expression was significantly changed in different brain areas. CONCLUSION:
      It was proved that CPP model can be used as an effective tool to investigate the
      mechanisms underlying drug-induced reinstatement of drug seeking after
      extinction, and that morphine induced CPP and drug primed reinstatement may
      involve activation of the transcription factor CREB in several brain areas,
      suggesting that the CREB and its target gene regulation pathway may mediate the
      basic mechanism underlying opioid dependence and its drug seeking behavior.

PMID- 16421966
TI  - Dendritic cell therapy with improved outcome in glioma multiforme--a case report.
AB  - Malignant gliomas are the most devastating tumors in clinical practice and have
      poorest survival. Immunological treatment of such patients may likely increase
      the survival and quality of life. Dendritic cells (DCs), most potent antigen
      presenting cells in combination with oral chemotherapeutic agents may be tried
      for patients giving consent to such treatment. We have successfully combined the
      two therapies in an adult male patient who was on downhill course after being
      operated on once with post operation chemotherapy and radiotherapy for glioma in
      the left parietal area. He received five dendritic cell therapy vaccines in
      combination with oral chemotherapy and responded dramatically having near normal
      quality of life for an additional five months with this regime, increasing the
      survival after operation to 11 months. This therapy is continuing with
      radiological betterment of the lesion. The DCs are matured with antigen extracted
      from wax embedded tissue at 6th day of culture. We feel that the treatment can be
      given to more number of patients to establish its efficacy for the dreaded cancer
      glioblastoma multiforme.

PMID- 16421968
TI  - Surgical results of pars plana vitrectomy combined with phacoemulsification.
AB  - OBJECTIVES: To evaluate the technical feasibility, safety, outcome, and incidence
      of complications after combined clear corneal phacoemulsification (PEA) with
      intraocular lens (IOL) implantation and vitreoretinal surgery. METHODS: Combined
      operations of PEA and PPV were performed on 52 eyes of 52 patients with cataract
      and vitreoretinal diseases. RESULTS: The mean follow-up time was (10.3+/-2.8)
      months. Postoperatively, visual acuity improved in 46 eyes (88.5%); was unchanged
      in 6 eyes (11.5%). The best-corrected visual acuities (BCVAs) were the following:
      20/40 or better (9 eyes), 20/50 to 20/100 (24 eyes), 20/200 (5 eyes), 20/400 (10
      eyes), and fingers counting (FC) to light perception (LP) (4 eyes). In 38 eyes
      BCVA was 20/200 or better, and in 9 eyes it was 20/40 or better postoperatively.
      Postoperative complications included posterior capsual opacification (7 eyes);
      secondary glaucoma (1 eye); and retinal detachment (2 eyes). CONCLUSION: Although
      further studies are indicated, our study suggests that the combined operation of
      PPV, PEA and IOL implantation is safe and effective for patients. The visual
      outcome and complications depended primarily on underlying posterior segment
      pathology and were not related to the combined procedure technique.

PMID- 16421969
TI  - Hemodynamic changes in depressive patients.
AB  - OBJECTIVE: This study is aimed at exploring the relationship between hemodynamic
      changes and depressive and anxious symptom in depression patients. METHODS: The
      cardiac function indices including the left stroke index (LSI), ejection fraction
      (EF), heart rate (HR), diastolic pressure mean (DPM), systolic pressure mean
      (SPM), left ventricle end-diastolic volume (LVDV), effective circulating volume
      (ECV), resistance total mean (RTM) and blood flow smooth degree (BFSD) were
      determined in 65 patients with major depressive disorders and 31 healthy normal
      controls. The clinical symptoms were assessed with Hamilton depression scale
      (HAMD) and Hamilton anxiety scale (HAMA). RESULTS: In patients with depression
      without anxiety, LSI, EF, LVDV, DPM, SPM, ECV, BFSD were significantly lower than
      those in controls, while RTM was higher than that in controls. Patients with
      comorbidity of depression and anxiety showed decreased LVDV, ECV, BFSD, and
      increased HR in comparison with the controls. The anxiety/somatization factor
      score positively correlated with LSI, EF, LVDV, but negatively correlated with
      RTM. There was negative correlation between retardation factor score and DPM,
      SPM, LVDV. CONCLUSION: The study indicated that there are noticeable changes in
      left ventricle preload and afterload, blood pressure, peripheral resistance, and
      microcirculation in depressive patients, and that the accompanying anxiety makes
      the changes more complicated.

PMID- 16421970
TI  - A case of overlapping Bickerstaff's brainstem encephalitis and Guillain-Barre
      syndrome.
AB  - OBJECTIVE: There is no report on Bickerstaff's brainstem encephalitis (BBE)
      patients in China. We here report the first case of BBE in China. METHODS:
      Clinical features, results of electromyography, electroencephalography (EEG),
      magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination were
      studied to clarify the characteristics of this syndrome. RESULTS: A 44-year-old
      man presented himself at our inpatient department with somnolence and dizziness
      as his initial symptoms. He developed multiple cranial nerves paralysis
      especially internal and external ophthalmoplegia, ataxia and tetraparesis within
      1 week. His condition rapidly deteriorated, and he experienced coma.
      Electromyography showed indications of peripheral nerve dysfunction,
      electroencephalography revealed loss of basic rhythm, MRI demonstrated high
      intensity abnormalities on T(2)-weighted images of medulla oblongata, and CSF
      albuminocytological dissociation was defined abnormally as high protein. Ten
      months later, he almost completely recovered. CONCLUSION: BBE, fisher syndrome
      (FS) and Guillain-Barre syndrome (GBS) are similar clinically; BBE and FS were
      proposed to be the variant of GBS.

PMID- 16421967
TI  - Video-assisted thoracic surgery--the past, present status and the future.
AB  - Video-assisted thoracic surgery (VATS) has developed very rapidly in these two
      decades, and has replaced conventional open thoracotomy as a standard procedure
      for some simple thoracic operations as well as an option or a complementary
      procedure for some other more complex operations. In this paper we will review
      its development history, the present status and the future perspectives.

PMID- 16421971
TI  - Inhibition of mitochondria responsible for the anti-apoptotic effects of
      melatonin during ischemia-reperfusion.
AB  - OBJECTIVE: To investigate a possible mechanism responsible for anti-apoptotic
      effects of melatonin and provide theoretical evidences for clinical therapy.
      METHODS: Ischemia-reperfusion mediated neuronal cell injury model was constructed
      in cerebellar granule neurons (CGNs) by deprivation of glucose, serum and oxygen
      in media. After ischemia, melatonin was added to the test groups to reach
      differential concentration during reperfusion. DNA fragmentation, mitochondrial
      transmembrane potential, mitochondrial cytochrome c release and caspase-3
      activity were observed after subjecting cerebellar granule neurons to oxygen
      glucose deprivation (OGD). RESULTS: The results showed that OGD induced typical
      cell apoptosis change, DNA ladder and apoptosis-related alterations in
      mitochondrial functions including depression of mitochondrial transmembrane
      potential (its maximal protection ratio was 73.26%) and release of cytochrome c
      (its maximal inhibition ratio was 42.52%) and the subsequent activation of
      caspase-3 (its maximal protection ratio was 59.32%) in cytoplasm. Melatonin
      reduced DNA damage and inhibited release of mitochondrial cytochrome c and
      activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of
      the mitochondria membrane potential. CONCLUSION: Our findings suggested that the
      direct inhibition of mitochondrial pathway might essentially contribute to its
      anti-apoptotic effects in neuronal ischemia-reperfusion.

PMID- 16421972
TI  - Surgical outcomes and strategy of hypertrophic obstructive cardiomyopathy.
AB  - OBJECTIVE: To evaluate the surgical clinical results of hypertrophic obstructive
      cardiomyopathy. METHODS: We retrospectively collected data on 24 patients who
      underwent surgical management in the past ten years in two hospitals in China and
      Madras Medical Mission in India. Myomectomy was carried out on all patients.
      Among them 3 patients underwent mitral valve replacement; 2 patients underwent
      mitral valve repair (anterior mitral leaflet plication); 2 patients underwent
      aortic valve replacement; 1 patient underwent aortic valve repair; 2 patients
      underwent aortic root replacement; 1 patient underwent Bentall's procedure and 1
      patient underwent coronary artery bypass grafting because of a breached muscle
      bridge. RESULTS: One patient died of post-operative heart failure. The mean
      follow-up time was 4.3 years. There was significant improvement in the
      symptomatic status. Sixteen patients were asymptomatic with good effort tolerance
      and only four patients had New York heart association (NYHA) Classes I-II due to
      associated valvular lesions. CONCLUSION: Our experience proved that symptomatic
      hypertrophic obstructive cardiomyopathy or non-symptomatic hypertrophic
      obstructive cardiomyopathy with combined heart disease is indication for surgery
      as surgical intervention could get better clinical results in this kind of
      patients compared with other non-surgical method because it beneficially reduces
      the systolic anterior motion (SAM) of the mitral valve leaflet, which could not
      be avoided by other non-surgical treatment.

PMID- 16421973
TI  - A study of the relationship between expression level of TRF1 protein and
      telomerase activity in human acute leukemia.
AB  - OBJECTIVE: To study the expression level of TRF1 (telomeric repeat binding factor
      1) protein in human acute leukemia and relationship between expression level of
      TRF1 protein and telomerase. METHODS: A quantitative Western-Blot technique was
      developed using anti-TRF1(33-277) monoclonal antibody and GST-TRF1 purity protein
      as a standard to further determine the expression level of TRF1 protein in total
      proteins extracted from clinical specimens. RESULTS: Bone marrow tissues of 20
      acute leukemia patients were studied, 11 healthy donors' bone marrows were taken
      as a control. The expression level of TRF1 protein was significantly higher
      (P<0.01) in normal bone marrow ((2.217+/-0.462) microg/microl) than that of acute
      leukemia patients ((0.754+/-0.343) microg/microl). But there was no remarkable
      difference between ALL and ANLL patients ((0.618+/-0.285) microg/microl vs
      (0.845+/-0.359) microg/microl, P>0.05). After chemotherapy, TRF1 expression level
      of patients with complete remission elevated ((0.772+/-0.307) microg/microl vs
      (1.683+/-0.344) microg/microl, P<0.01), but lower than that of normal ((2.217+/
      0.462) microg/microl, P<0.01). There was no significantly difference after
      chemotherapy ((0.726+/-0.411) microg/microl vs (0.895+/-0.339) microg/microl,
      P>0.05). TRF1 expression level of patients with complete remission is higher than
      that of patients without complete remission ((1.683+/-0.344) microg/microl vs
      (0.895+/-0.339) microg/microl, P<0.01). All samples were determined for
      telomerase activity. It was confirmed that the activity of telomerase in normal
      bone marrow was lower than that of acute leukemia patients ((0.125+/-0.078)
      microg/microl vs (0.765+/-0.284) microg/microl, P<0.01). There was no significant
      difference of expression level of TRF1 protein between ALL and ANLL patients
      ((0.897+/-0.290) microg/microl vs (0.677+/-0.268) microg/microl, P>0.05). After
      chemotherapy, telomerase activity of patients with complete remission decreased
      ((0.393+/-0.125) microg/microl), but was still higher than that of normal
      ((0.125+/-0.078) microg/microl, P<0.01). CONCLUSION: The expression level of TRF1
      protein has correlativity to the activity of telomerase (P<0.001).

PMID- 16421974
TI  - The role of genomics in medicine--past, present and future.

PMID- 16421975
TI  - Genomics and world health: hopes and realities.
AB  - Due to lack of appreciation of the complexities of the interactions between
      nature and nurture, claims for the rapid improvements in medical care following
      the human genome project have been exaggerated. Although some progress has been
      made in certain fields, the full scope of genomic medicine may not be realised
      for many years.

PMID- 16421976
TI  - Clinical cytogenetics and molecular cytogenetics.
AB  - The short report will be focused on helping our students to understand commonly
      used conventional and cutting edge cytogenetic techniques and their clinical
      applications, the advances and drawbacks of each technique, and how to pick the
      right test(s) for a specific patient in order to achieve a proper diagnosis
      efficiently and economically.

PMID- 16421977
TI  - Human cancer genetics.
AB  - The short report will be focused on the genetic basis and possible mechanisms of
      tumorigenesis, common types of cancer, the importance of genetic diagnosis of
      cancer, and the methodology of cancer genetic diagnosis. They will also review
      presymptomatic testing of hereditary cancers, and the application of expression
      profiling to identify patients likely to benefit from particular therapeutic
      approaches.

PMID- 16421978
TI  - Human biochemical genetics: an insight into inborn errors of metabolism.
AB  - Inborn errors of metabolism (IEM) include a broad spectrum of defects of various
      gene products that affect intermediary metabolism in the body. Studying the
      molecular and biochemical mechanisms of those inherited disorder, systematically
      summarizing the disease phenotype and natural history, providing diagnostic
      rationale and methodology and treatment strategy comprise the context of human
      biochemical genetics. This session focused on: (1) manifestations of
      representative metabolic disorders; (2) the emergent technology and application
      of newborn screening of metabolic disorders using tandem mass spectrometry; (3)
      principles of managing IEM; (4) the concept of carrier testing aiming prevention.
      Early detection of patients with IEM allows early intervention and more options
      for treatment.

PMID- 16421979
TI  - Genetics of complex diseases.
AB  - Approaches to the study of the genetic basis of common complex diseases and their
      clinical applications are considered. Monogenic Mendelian inheritance in such
      conditions is infrequent but its elucidation may help to detect pathogenic
      mechanisms in the more common variety of complex diseases. Involvement by
      multiple genes in complex diseases usually occurs but the isolation and
      identification of specific genes so far has been exceptional. The role of common
      polymorphisms as indicators of disease risk in various studies is discussed.

PMID- 16421981
TI  - Baxter Healthcare infusion pump recall.

PMID- 16421980
TI  - Pharmacogenetics, pharmacogenomics and ecogenetics.
AB  - Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in
      drug effectiveness and adverse drug reactions. The promise of a personalized
      medicine is beginning to be explored but requires much more clinical and
      translational research. Specific DNA abnormalities in some cancers already have
      led to effective targeted treatments. Racially determined frequency differences
      in pharmacogenetic traits may affect choice of treatment requiring specific
      testing rather than basing treatments according to racial designation. The role
      of genes in variable responses to foreign chemicals (xenobiotics) has been termed
      ecogenetics or toxicogenetics raising problems in public health and occupational
      medicine. Nutrigenetics refers to genetic variation in response to nutrients and
      may affect nutritional requirements and predisposition to chronic disease.

PMID- 16421982
TI  - Several AIDS drugs tentatively approved.

PMID- 16421983
TI  - Warning on fentanyl patch.

PMID- 16421984
TI  - Meningococcal vaccine for adolescents and college freshmen.

PMID- 16421985
TI  - Public health advisory for mifepristone.

PMID- 16421986
TI  - Pet turtles may be harmful to your health.

PMID- 16421987
TI  - New whooping cough vaccine for adolescents and adults.

PMID- 16421988
TI  - Decreasing your risk of abnormal heart rhythm.

PMID- 16421989
TI  - Gastric bypass. Surgery's role in treating obesity.

PMID- 16421990
TI  - On occasion, my pulse rate climbs rapidly, only to return to normal a minute or
      two later. I don't experience any chest pain or other discomfort. What could
      cause this?

PMID- 16421991
TI  - I saw an advertisement for a weight-loss product. When I called the manufacturer
      to find out what's in it, I was told they couldn't tell me because it's a
      "proprietary blend." What does that mean?

PMID- 16421992
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 16421993
TI  - Familial hypercholesterolemia.

PMID- 16421994
TI  - China's biotech experiments.

PMID- 16421995
TI  - Lament of the really crummy deal.
AB  - You've heard enough bragging about the great licensing successes of your
      colleagues. But for each successful deal, there is at least one total disaster
      that they try to forget. It's time to pull back the curtain and talk about some
      truly lousy deals.

PMID- 16421997
TI  - [Acute bronchiolitis in infants].

PMID- 16421996
TI  - Reprinting the classic article on USPHS evaluation methods for measuring the
      clinical research performance of restorative materials.

PMID- 16421998
TI  - [Update on bronchial hyperreactivity after bronchiolitis].

PMID- 16421999
TI  - [Review of the definition of bronchopulmonary dysplasia].

PMID- 16422000
TI  - [Respiratory syncytial virus prevention in infants at high risk of
      rehospitalization].

PMID- 16422001
TI  - NY: RN falsely documents 'normal' GYN exam: termination & denial of unemployment
      benefit.

PMID- 16422002
TI  - Interleukin (IL)-6, interleukin (IL)-8 levels and cellular composition of the
      vitreous humor in proliferative diabetic retinopathy, proliferative
      vitreoretinopathy, and traumatic proliferative vitreoretinopathy.
AB  - PURPOSE: To investigate the interleukin (IL)-6 levels, IL-8 levels, and cellular
      composition of the vitreous humor in patients with proliferative diabetic
      retinopathy (PDR), proliferative vitreoretinopathy (PVR), and traumatic PVR.
      METHODS: Vitreous samples from 14 patients with PDR, 10 patients with PVR, and 10
      patients with traumatic PVR were analyzed. Fifteen cadaver eyes were used as
      controls. Cytokine levels were measured by ELISA. RESULTS: Elevated IL-6 levels
      were detected in the vitreous of 12 (85.7%) of the PDR patients, eight (80%) of
      the PVR patients, and all (100%) of the traumatic PVR patients. None of the
      control IL-6 results were elevated. Vitreous IL-8 levels were elevated in 12
      (85.7%) of the PDR patients, six (60%) of the PVR patients, all (100%) of the
      traumatic PVR patients, and one (6.7%) of the control eyes. Cytological
      examination of the vitreous specimens revealed a predominance of macrophages
      (50%) in the PDR samples and a predominance of retinal pigment epithelial (RPE)
      cells (60%) in the PVR samples. In contrast, neutrophils predominated (88%) in
      the traumatic PVR samples. CONCLUSION: The findings suggest that IL-6 and IL-8
      may be involved in the pathogenesis of PDR, PVR, and traumatic PVR. High
      proportions of RPE cells and macrophages are associated with elevated IL-6 and IL
      8 levels in the vitreous of PDR and PVR patients; however, the fact that these
      cells are not predominant in traumatic PVR suggests that different immune
      response mechanisms may be active in the pathogenesis of these disorders.

PMID- 16422003
TI  - Adventitious viruses and smallpox vaccine.

PMID- 16422004
TI  - Fluoroquinolone use in food animals.

PMID- 16422005
TI  - Ehrlichia ruminantium, Sudan.

PMID- 16422006
TI  - Borrelia spielmanii erythema migrans, Hungary.

PMID- 16422007
TI  - Profiling Mycobacterium ulcerans with hsp65.

PMID- 16422008
TI  - Spelling of emerging pathogens.

PMID- 16422009
TI  - Staphylococcus aureus bacteremia, Europe.

PMID- 16422010
TI  - Family clustering of avian influenza A (H5N1).

PMID- 16422011
TI  - Imported tickborne relapsing fever, France.

PMID- 16422012
TI  - Neonatal Moraxella osloensis ophthalmia.

PMID- 16422013
TI  - African tick-bite fever in French travelers.

PMID- 16422014
TI  - Your health in the 21st century. The science of drugs.

PMID- 16422016
TI  - Bibliography. Current world literature. Ocular manifestations of systemic disease
      part II.

PMID- 16422015
TI  - Bibliography. Current world literature. Oculoplastic and orbital surgery.

PMID- 16422017
TI  - Evidence-based medicine.
AB  - Evidence-based medicine (EBM) describes a structured (non-consensus-based)
      process, in which medical literature is assessed critically to define the value
      of different therapeutic interventions. Ultimately, the goal is to improve both
      physician decision making and patient outcome. These assessments begin by
      defining the specific clinical questions to be answered. Following a structured
      literature search, evidence that bears on these questions is assembled and
      classified with respect to the quality of the evidence provided by each study.
      Lastly, using a set of pre-specified rules, this evidence is translated into
      specific conclusions and recommendations. Its relative objectivity means that
      evidence-based medicine can be a powerful tool for practising physicians. As a
      result, it is important for them to become familiar with this analytical method.

PMID- 16422018
TI  - Antipsychotic drugs and schizophrenia.

PMID- 16422019
TI  - Antipsychotic drugs and schizophrenia.

PMID- 16422020
TI  - Antipsychotic drugs and schizophrenia.

PMID- 16422021
TI  - Vasodilators in aortic regurgitation.

PMID- 16422022
TI  - Vasodilators in aortic regurgitation.

PMID- 16422023
TI  - Vasodilators in aortic regurgitation.

PMID- 16422024
TI  - Asbestos exposure and serum osteopontin.

PMID- 16422025
TI  - Malignant mesothelioma.

PMID- 16422026
TI  - Malignant mesothelioma.

PMID- 16422027
TI  - Letter of retraction.

PMID- 16422028
TI  - Efficacy and tolerability of a topical erythromycin/tretinoin combination
      preparation in acne treatment: post-marketing surveillance study involving over
      6500 patients.
AB  - The good efficacy and tolerability of an alcoholic erythromycin/tretinoin
      solution was confirmed in a multicentre data investigation of over 6500 patients.
      The mean score for comedones declined clearly from 1.9 to 0.9 during treatment
      (average duration 70 days). The score for papules and pustules was reduced from
      1.6 to 0.5. Overall medical assessment indicated 'very good' to 'good' efficacy
      in 86.1% of documented cases. Adverse drug reactions during treatment were mostly
      only very mild and were nearly always the known symptoms of redness, scaling,
      dryness and itching. Overall assessment of tolerability was 'very good' or 'good'
      in 88.1% of cases.

PMID- 16422029
TI  - Ratio of inhaled corticosteroid to bronchodilator treatment and asthma
      hospitalisation.
AB  - BACKGROUND: Previous research based on aggregated data has led to conflicting
      interpretations of the relationship between the corticosteroid:bronchodilator
      (C:B) ratio and outcome measures. OBJECTIVES: To assess whether the C:B ratio is
      associated with hospital contact for asthma at individual patient level. METHODS:
      The study was a retrospective multivariate analysis, using data from the U.K.
      General Practice Research Database from 1993 to 1996. The subjects were 3465
      asthma-diagnosed patients receiving bronchodilator and corticosteroid medication.
      The main outcome measures were asthma-related hospital contacts. RESULTS: There
      was an inverse association between the C:B ratio and hospital contact after
      controlling for age. The odds ratio for the C:B ratio was 0.87 (95 % CI 0.73
      0.98) and 1.04 (95% CI 1.01-1.07) for five-year agebands among patients aged five
      years and over. There was no systematic relationship between the C:B ratio and
      hospital contacts for patients aged under five years. CONCLUSION: The results of
      this study show that higher C:B ratios are associated with lower levels of
      hospital contacts at patient level, although there are exceptions possibly linked
      to disease severity. For patients under five years, the ratio may not be a good
      outcome measure, perhaps owing to the difficulty in diagnosing asthma or poor
      compliance.

PMID- 16422030
TI  - Effect of rifaximin on intestinal bacterial overgrowth in Crohn's disease as
      assessed by the H2-Glucose Breath Test.
AB  - The occurrence of intestinal bacterial overgrowth in patients with Crohn's
      Disease (CD) has been described and antimicrobial treatment has been shown to be
      effective in reversing this condition. However, the mechanisms underlying the
      efficacy of antimicrobial therapy are still only partially known. The aim of the
      present study was to evaluate the effect of a non-absorbable antibiotic
      (rifaximin) in comparison to placebo on bacterial overgrowth in patients with CD.
      METHODS: Fourteen patients with inactive CD of the ileum and bacterial
      overgrowth, as assessed by the hydrogen breath test, were blindly allocated to
      receive rifaximin (1200 mg/day) or placebo t.i.d. for one week. A hydrogen breath
      test, and clinical and biochemical parameters were further performed 14 days and
      30 days after starting treatment. RESULTS: After 14 days, the hydrogen breath
      test proved to be negative in seven out of seven patients treated with rifaximin
      (p < 0.05), and in two out of seven in the placebo group (p = ns). After 30 days,
      the hydrogen breath test was positive in all patients of the rifaximin and
      placebo group, respectively. No changes in the CDAI score were documented in any
      patients. CONCLUSIONS: Short-term administration of rifaximin is effective in the
      therapy of bacterial overgrowth in patients with inactive CD of the ileum, thus
      suggesting that the control of luminal bacterial growth could be useful in the
      management of these patients. However, since we observed a decline with time in
      this positive effect, further studies are needed to identify the most appropriate
      therapeutic strategies.

PMID- 16422031
TI  - Treatment of dyslipidaemias in patients with established vascular disease: a
      revival of the fibrates.
AB  - The key 'statin trials' focussed on the beneficial effect of lowering the
      circulating concentrations of low-density lipoprotein cholesterol (LDL). However,
      epidemiological surveys, mainly based on healthy populations, indicate that other
      lipid-related variables, such as high-density cholesterol (HDL), triglycerides
      (TG), dense LDL subfraction distribution, and possibly lipoprotein (a) (Lp(a)),
      are also predictors of vascular events. Furthermore, TG and HDL levels influenced
      outcome within some of the statin trials. Plasma fibrinogen levels have also been
      shown to be powerful predictors of vascular risk in healthy subjects and patients
      with established ischaemic heart disease. The fibrates exert beneficial effects
      on all these variables that predict vascular events. The results from recent
      trials, the Bezafibrate Infarction Prevention (BIP) study and the Veterans
      Administration HDL Intervention Trial (VA-HIT) have revived our interest in
      fibrates. These trials involved bezafibrate and gemfibrozil that have a
      relatively poor LDL-lowering capacity. Therefore, the benefits reported in BIP
      and VA-HIT must be attributed to actions on variables other than a reduction in
      LDL quantity. Ciprofibrate and fenofibrate have significantly greater LDL
      lowering capacity than bezafibrate or gemfibrozil. This advantage may render them
      more effective, especially since they retain the additional beneficial actions
      associated with this class of lipid-lowering drugs.

PMID- 16422033
TI  - Antipsychotics--the future of schizophrenia treatment.
AB  - Schizophrenia is a debilitating mental disorder affecting up to five in every
      thousand people. Although specialist psychiatrists are initially responsible for
      treating patients suffering from acute schizophrenia, the current structure of
      mental healthcare in the U.K. puts the onus for the delivery of maintenance
      therapy of discharged patients on to the general practitioner. It is crucial,
      therefore, that the general practitioner is aware of all available therapies for
      the effective, long-term, community-based treatment of patients with
      schizophrenia. The so-called typical antipsychotics effectively treat the
      positive but not the negative symptoms of schizophrenia, and up to 40% of
      patients are nonresponders. These antipsychotics, however, are associated with
      high levels of extrapyramidal side-effects (EPS), which are the main cause of
      patient non-compliance and their subsequent relapse and hospital readmission.
      Clozapine, the first atypical antipsychotic, may cause severe agranulocytosis and
      patients must undergo regular haematological monitoring, which is both costly and
      a factor unlikely to foster patient compliance. In contrast, newly developed
      atypical antipsychotics, such as olanzapine and quetiapine, are not only
      efficacious in treating the symptoms of schizophrenia, but also give rise to
      fewer EPS and are generally better tolerated than clozapine. In particular,
      olanzapine and quetiapine are not associated with severe agranulocytosis.
      Atypical antipsychotics, therefore, have the potential to enhance patient
      compliance and thus ease the general practitioner's problems of providing long
      term and effective treatment for patients with schizophrenia.

PMID- 16422032
TI  - Hypertension control in the elderly with amlodipine.
AB  - Treatment of hypertension in the elderly reduces the incidence of cardiovascular
      events. Some classes of antihypertensive drugs, including long-acting
      dihydropyridine calcium channel blockers such as amlodipine, can be prescribed in
      the presence of comorbid conditions. The results of clinical trials support the
      use of long-acting dihydropyridine calcium channel blockers in the elderly;
      amlodipine has been shown to be effective and well tolerated in the elderly
      population.

PMID- 16422034
TI  - Targeting Parkinson's disease--the case for early referral.
AB  - Parkinson's disease (PD) is a chronic and disabling condition, for which
      guidelines for best practice have recently been implemented in the U.K. One of
      the key issues discussed is the provision of a continuum of care by a
      multidisciplinary team, which must comprise professionals with specialist
      expertise, including a PD specialist nurse and patient carer(s). Emphasis is
      placed on the importance of referral of de novo patients to specialist centres
      for confirmation of diagnosis and management. A synopsis of the classes of drugs
      available, differential diagnosis and the role of drug treatment in PD are also
      presented. The guidelines highlight that revision of national guidelines to form
      local protocols and working practices will improve and integrate care for PD
      patients. The significance of teamwork and good communication between primary
      care specialists in the management of PD is emphasised throughout.

PMID- 16422035
TI  - Management of data used in clinical trials which is unevenly distributed at
      baseline.
AB  - In this study, 63 healthy adult males were selected for participation in a
      clinical trial. After initial screening to determine their suitability for
      participation in the trial, an appointment was scheduled for a professional
      prophylaxis to derive baseline data and to instruct volunteers in the use of a
      standard oral hygiene regimen for the trial. Volunteers were then randomly
      assigned to test and control groups. Follow-up appointments were scheduled two
      and four weeks thereafter for collection of data. The presence of dental plaque
      and calculus was assessed at each appointment. Data was to be analysed by using a
      Student's 't'-test for paired data, but significant differences in the plaque
      scores were found between the test and control groups at baseline. As a result,
      the data could not be analysed in this way to obtain a meaningful result. An
      initial scatter plot of the data revealed six subjects whose plaque scores varied
      considerably from the group. The aim of this analysis was to evaluate how two
      different approaches to statistical analysis of data in which significant
      differences between test and control groups at baseline might affect the
      inferences drawn from the data. Reasons for significant differences in baseline
      data in randomly selected groups of volunteers were considered, as well as
      methods of avoiding this situation. Suggestions on the management of situations
      in which databases significantly differ include the elimination of 'outliers' and
      the use of techniques like the Standard Normal Deviate (SND). The data for this
      study were analysed using these techniques. Although no statistical differences
      were identified between the two methods of analysis, numerical differences were
      evident which altered with the type of analysis used. It was concluded that
      techniques for transformation of the data, like those used in this study, made no
      difference to the results of subsequent statistical analysis by comparison with
      the original data set. The influence of sample selection and analysis of data on
      the results of clinical trials are discussed. The difficulties in interpretation
      of the results of statistical analyses were highlighted. The influence of
      imbalances in the data set on the interpretation of the results of statistical
      analysis was shown to be minimal in this clinical trial.

PMID- 16422036
TI  - One of life's journeys.

PMID- 16422037
TI  - Stroke unit fall prevention: an interdisciplinary, data-driven approach.

PMID- 16422038
TI  - Stroke prevention education in the Hispanic community.
AB  - The Hispanic population is the fastest growing minority population in the United
      States. Little research has been done to assess the stroke risk in the Hispanic
      population, which has a higher prevalence of hypertension, diabetes, alcohol use,
      and physical inactivity. Healthcare professionals therefore are faced with the
      management and education of a cultural group with unfamiliar health beliefs. To
      decrease the risk of stroke, a culturally sensitive program that combines
      education and risk identification is needed. This article identifies the
      development of a stroke education and screening program for Hispanics.

PMID- 16422039
TI  - Medications, comorbidities, and medical complications in stroke survivors: the
      CAReS study.
AB  - Stroke survivors enter rehabilitation units with many medical comorbidities and
      often experience significant complications during their stays. The 97 stroke
      survivors discharged home in this study received prescriptionsfor a mean of 11.3
      medications from 5.4 different drug classifications. There were significant
      correlations between the number of comorbidities and after stroke complications
      and the number of different classifications of drugs that were ordered. This
      article (1) identifies the types of medications prescribed for stroke survivors
      who are being discharged home from rehabilitation, (2) explores correlations
      between medication prescriptions and the number of stroke-related comorbidities
      and medical complications, (3) identifies the cost of medications and the
      potential effect of medication costs on stroke survivors, and (4) discusses the
      nurse's role in preparing stroke survivors and their caregivers for medication
      use after discharge. Rehabilitation nurses bear the major responsibility for
      teaching stroke survivors and their caregivers about their discharge medications.

PMID- 16422040
TI  - Testing a model of post-stroke exercise behavior.
AB  - Stroke is the leading cause of disability in older Americans, and survivors tend
      to be sedentary, thereby risking loss of functional gains achieved during
      rehabilitation and increasing cardiovascular risk. Studies of motivation to
      exercise in older adults suggest that self-efficacy and outcome expectations are
      key determinants of initiation and adherence to exercise programs. This study
      tested a theoretical model of physical activity in stroke survivors. A survey of
      exercise beliefs and patterns was sent to National Stroke Association stroke
      support groups. Responses from 312 stroke survivors (mean age 63 years, 57%
      female, 70% White) indicated that only 31% exercised four times weekly. Self
      efficacy and outcome expectations for exercise, before exercise history, and
      physician recommendation all directly and indirectly influenced self-reported
      exercise behavior and accounted for 33% of the total variance in exercise
      behavior. Model testing supported the theory and the model fit the data.
      Interventions to strengthen self-efficacy and outcome expectations for exercise,
      along with reminders for clinicians to encourage regular exercise programs, may
      increase the likelihood of initiating and maintaining an exercise program,
      potentially improving physical function and cardiovascular fitness in this
      population.

PMID- 16422041
TI  - FIM score, FIM efficiency, and discharge disposition following inpatient stroke
      rehabilitation.
AB  - The Functional Independence Measure (FIM) is a widely accepted scale used to
      measure the functional abilities of patients undergoing rehabilitation. Scores at
      the extremes of this scale correlate with discharge disposition, while midrange
      scores are less well understood. This study evaluated the rate of FIM change with
      time ("efficiency"), admission and discharge FIM scores, and discharge
      disposition of 748 patients who underwent stroke inpatient rehabilitation.
      Patients with low scores at admission or discharge were likely to be discharged
      to a facility (63% and 78%, respectively), and those with high scores at
      admission or discharge almost always returned home (88% and 81%, respectively).
      Those with midrange scores at admission were more likely to return home (62%)
      than those with similar scores at discharge (33%). Greater FIM efficiency scores
      were associated with home discharge. Findings provide insight into discharge
      planning for stroke patients and indicate the need for more detailed evaluation
      of the midrange group.

PMID- 16422042
TI  - Caregiver perspectives of memory and behavior changes in stroke survivors.
AB  - Post-stroke memory and behavior changes (MBC) are associated with negative
      outcomes for stroke survivors and caregivers. This article describes the types of
      MBC that occur most frequently and caregivers' responses to these behaviors. Data
      were obtained through in-person interviews and administration of questionnaires
      to 132 caregivers of first-time stroke survivors 3-9 months after stroke. MBC
      were measured with a modified version of a Memory and Behavior Problems
      checklist. On average, caregivers reported 7.7 +/- 3.6 (range 0-17) behaviors.
      Common stroke survivor MBC included appearing sad or depressed, interrupting the
      caregiver, and being restless or agitated. These MBC were distressing to
      caregivers. Caregivers may not recognize some MBC as potential symptoms of
      depression. In addition, caregiver misunderstanding of the amount of control
      survivors may have over some behaviors has implications for rehabilitation and
      caregivers' responses to these changes.

PMID- 16422043
TI  - Outcomes among family caregivers of aphasic versus nonaphasic stroke survivors.
AB  - Adverse consequences are known to occur in family members responsible for
      providing care to stroke survivors. However, the differential effect of aphasic
      versus nonaphasic stroke on caregivers has not been well studied. This study
      compares selected outcomes (e.g., perceived task difficulty, depressive symptoms,
      and other negative stroke-related outcomes) among caregivers of aphasic (n = 46)
      and nonaphasic (n = 113) stroke survivors. Results indicated that caregivers of
      aphasic survivors perceived greater difficulty with tasks and had more negative
      stroke-related outcomes than caregivers of nonaphasic survivors. Communication
      with the survivor was rated as most upsetting and difficult by caregivers in the
      aphasic group, followed by managing behaviors. Lack of time for family and
      friends was evident. Female caregivers and caregivers of survivors with self-care
      deficits also perceived greater difficulty with tasks and negative outcomes.
      Comprehensive assessment of the unique needs of caregivers of aphasic survivors
      is suggested for more individualized nursing interventions.

PMID- 16422044
TI  - The evolution of hospice: from volunteer inception to professional business.

PMID- 16422045
TI  - A tribute to Susan Goldwater Levine and Hospice of the Valley.
AB  - Hospice of the Valley has clearly won a place in hearts and minds of the citizens
      of the Greater Phoenix/Scottsdale Community. This can be seen in the thousands of
      letters it has received such as the one from Mrs. C.S. of Tempe, Arizona who
      said: "I shall never be able to repay Hospice of the Valley for the tender loving
      care they gave my husband, and for the wonderful physical and emotional support
      they gave me when I didn't know where to turn to or how to cope. My love and
      prayers are with you forever." It can be seen in the fact that many of the
      original volunteers which included Mary-Audrey Mellor, Susan Cohill, Sandy Getz,
      Lyn Laflin, Julie Louis, Julie Perkins, Niki Robertshaw and Gay Wray are still
      involved. It can be seen in the growth of the organization and in the creation of
      some 16 (by the end of next year) inpatient facilities. It is evident in the
      involvement with major corporations and in the support of prominent political
      figures. HOV today stands as a model of all the best that hospice can be; a
      testimony to what can happen when good men and women work together in their
      mutual interest. Hospice of the Valley, has already had a profound effect on
      national hospice policy. Through the leadership of Ms. Levine, who last month
      took over the reigns from the esteemed Carla Braveman, to become Chairman of the
      Hospice Association of America, HOV will continue to help forge national policy.
      For many years to come, Hospice of the Valley will serve as a beacon to light the
      path for those who follow in the cause of humanitarian care for infirm and
      terminally ill Americans.

PMID- 16422046
TI  - Will I ever be normal?

PMID- 16422047
TI  - How to measure your organization's performance in one easy lesson.

PMID- 16422048
TI  - Best practices in nursing staff retention for hospice care organizations.

PMID- 16422049
TI  - A patient-centered approach to comfort assessment.

PMID- 16422050
TI  - Using outcome measures to drive hospice operating strategy.

PMID- 16422052
TI  - Integrative therapies: a valuable role in patient care.

PMID- 16422051
TI  - Telehospice and its use in home hospice care delivery today.

PMID- 16422053
TI  - The gift of dying at home alone.

PMID- 16422054
TI  - Hospice's high touch approach enhanced by telecommunication.

PMID- 16422055
TI  - Selling hospice services.

PMID- 16422056
TI  - Q & A: you ask and Sam answers.

PMID- 16422057
TI  - Quo Vadis Hospice?

PMID- 16422058
TI  - Schering-Plough manufactures do-it-yourself vaccinations.

PMID- 16422059
TI  - How to move the animal welfare issue forward.

PMID- 16422060
TI  - An ethicist's commentary on whether a veterinarian should report an owner with
      pit-bull puppies.

PMID- 16422061
TI  - The power of verbal treatment settings.

PMID- 16422062
TI  - The effect of postparturient urogenital diseases on the lifetime reproductive
      performance of sows.
AB  - To prove the effect of postparturient swine urogenital disease (SUGD) on
      reproductive performance, culled sows with SUGD in their previous history
      (n=1363) were subjected to retrospective lifetime production analysis. The sows
      were assigned to parity groups 1, 2 to 6, and >6. Bacterial flora of vulval
      discharges were evaluated. Parity 1 sows had a lower percentage of SUGD than did
      sows of parity 2 to 6 and parity >6 (P < 0.05 and P < 0.01, respectively).
      Compared with parity 2 to 6 sows, parity 1 and parity >6 sows had lower (P <
      0.001) conception, farrowing and adjusted farrowing rates, lifetime average total
      born, live-born litter sizes, stillbirth rates, and weaning litter weights
      compared with animals culled for other reasons than SUGD. The conclusions are
      that high parity sows have a higher occurrence of postparturient SUGD and that
      higher parity sows with postparturient SUGD have a lower performance compared
      with lower parity sows with postparturient SUGD.

PMID- 16422063
TI  - A retrospective study of the causes of morbidity and mortality in farmed elk
      (Cervus elaphus).
AB  - A survey of North American farmed elk (Cervus elaphus) producers was performed to
      determine the causes of sickness and mortality in farmed elk and to estimate
      mortality rates. Records over a 10-year period from 8 North American veterinary
      diagnostic pathology laboratories were also examined and summarized. The primary
      diagnosis for each record was used to classify diseases into categories such as
      parasitic, infectious, toxicological, and neoplastic. Nonspecific trauma was the
      most frequently reported known cause of mortality in both sexes and all age
      classes by elk producers. Ranked on perceived economic importance, producers
      cited trauma, chronic wasting disease, calf scours, dystocia, pneumonia, winter
      tick, tuberculosis, and grain overload. One-year mortality rates for adults and
      yearlings were 2.6% and 2.7%, respectively. Mortality rates for male and female
      adult animals were 2.4% and 2.7%, respectively. In general, the major findings of
      the survey matched reported causes for mortality provided by elk producers.

PMID- 16422064
TI  - Sudden cardiac death associated with occult hypertrophic cardiomyopathy in a dog
      under anesthesia.
AB  - A 6-year-old, 3.0 kg, neutered female, Yorkshire terrier was referred for
      orthopedic surgery. Cardiac arrest followed unsuccessful treatment of bradycardia
      and systemic arterial hypotension under general anesthesia. Postmortem
      examination revealed hypertrophic cardiomyopathy. A possible relationship between
      treatment of bradycardia, systemic arterial hypotension, and sudden cardiac death
      is described.

PMID- 16422065
TI  - The prevalence of milk and serum antibodies to Mycobacterium avium subspecies
      paratuberculosis in dairy herds in Ontario.
AB  - This study randomly surveyed 50 dairy herds in Ontario; 18% and 30% of herds had
      2 or more milk or serum enzyme-linked immunosorbent assay (ELISA)-positive cows,
      respectively. The apparent cow level prevalence was 1.7% and 2.6% on the milk and
      serum ELISA, respectively. The serum and milk assays agreed moderately.

PMID- 16422067
TI  - Amended health of animals regulations prohibiting the transport of nonambulatory
      animals.

PMID- 16422066
TI  - Suspected Clostridium difficile-associated hemorrhagic diarrhea in a 1-week-old
      elk calf.
AB  - Clostridium difficile-associated diarrhea was suspected in a 1-week-old elk
      (Cervus elaphus) calf. The isolation of a toxigenic strain of C. difficile from a
      diarrheic fecal sample, along with exclusion of other enteropathogens, formed the
      basis of this presumptive diagnosis. Further study is indicated to evaluate the
      role of C. difficile in neonatal diarrhea in elk.

PMID- 16422068
TI  - What's new in orthopedics in 2005--part I.

PMID- 16422069
TI  - Case study in canine intestinal lymphangiectasia.
AB  - A 9.52 kg, 9-year-old, spayed female beagle was presented with the chief
      complaint of abdominal distention of 1 week's duration. A presumptive diagnosis
      of canine intestinal lymphangectasia was arrived at by exclusion of other causes
      for the patient's ascites. The patient was successfully treated with dietary
      modification and immunosuppressive therapy.

PMID- 16422070
TI  - Avian pox virus infection in a mourning dove.
AB  - An adult mourning dove (Zenaidura macroura) was presented with dyspnea, poor body
      condition, and poor flight endurance. Nodular lesions were visible on the cere,
      both feet, and skin covering the pectoral region. Histopathological examination
      revealed epithelial hyperplasia with eosinophilic intracytoplasmic inclusion
      bodies consistent with Avipoxvirus infection.

PMID- 16422071
TI  - Veterinary diagnostic imaging. Malignant pheochromocytoma of the left adrenal
      gland invading the caudal vena cava, accompanied by a cortisol secreting
      adrenocortical carcinoma of the right adrenal gland.

PMID- 16422072
TI  - [A medical image fusion method based on fuzzy mathematics].
AB  - In this paper, a method based on fuzzy mathematics to fuse multimodality medical
      images was presented. The improved FCM algorithm was adopted to segment images,
      and automatic fuzzy redistribution algorithm to define the subject degree. 16
      different combinations of image tissues and 16 context relations, 256 models
      altogether, were considered. The result showed that the method had the great
      ability of anti-error and anti-segmentation interference and had the
      characteristics of robustness, quickness, and accuracy.

PMID- 16422073
TI  - [Frequency characteristic of diseased breast tissues detected by electrical
      impedance scanning].
AB  - The rules of conductance parameters on diseased breast tissue, which change with
      the driven frequency, are studied by use of electrical impedance scanning. This
      work is intended to provide a basis for further examination of breast. We have
      obtained conductance parameters' frequency characteristic of three kinds of
      breast diseases, i.e. invasive ductal carcinoma, neoplastic hyperplasia, and
      mastopathia. And by comparison, we find that the frequency characteristic of the
      diseased breast tissues is different from that of the peripheral normal tissues,
      and the frequency characteristic shows differences among the three kinds of
      diseased breast tissues. So, we are able to identify the kind of breast disease
      by its frequency characteristic.

PMID- 16422074
TI  - [Design of a quantitative analysis software system for myocardial contrast
      echocardiography].
AB  - This article reports a quantitative analysis software system for myocardial
      contrast echocardiography (MCE). It can measure the signal intensity of grayscale
      images and power Doppler images, draw the time-intensity curves of variations on
      the intensity of microbubbles scattering in subendocardial layer and
      subepicardial layer with the pulsing intervals, and estimate the hemodynamic
      parameters by nonlinear regression analysis. This system has been applied to a
      study on 20 healthy volunteers, and the results suggest that the software has the
      capacity for bringing the quantitative analysis of MCE to success. The MCE
      software system conforms to the DICOM standard and can be integrated into PACS.

PMID- 16422075
TI  - [Quantitative gait evaluation using principal component analysis].
AB  - Evaluation of human gait function is of great significance in clinical medicine
      and rehabilitation engineering. A quantitative gait evaluation method using
      principal component analysis was proposed. The evaluation steps included that a
      series of characteristic index was performed by the gait parameters with a gait
      detection, and the index was normalized, quantified and summarized by principal
      component analysis. Then the evaluation results were shown in formulation,
      figures and tables. The examples showed that this system could evaluate the
      recovery of the gait by treatment.

PMID- 16422076
TI  - [Effective control of excitable waves in 2D cardiac excitable media].
AB  - We propose a method for effective control of patter on dissipative system by use
      of little perturbation analysis, and apply this nonuniform feed back method to
      control the polarization wave of heart represented by FHN equation. In the
      numerical experiment, we successfully alter the propagating direction of planar
      waves and drift the spiral waves to boundary without resonant repulsion. The
      effective control of the excited system will be used to study the mechanism of
      defibrillation and that is our interesting work.

PMID- 16422077
TI  - [Bayesian representation of prior information and MCMC method in microwave
      imaging].
AB  - Microwave imaging for dielectric objects was considered in this paper. Applying
      Bayesian approach to represent prior information about permittivity distribution
      of observed object by prior probability density and combine measurements
      information of scattering field, we obtained posterior probability density that
      included synthetic information about the observed object. And then, Gibbs
      sampler, one of Markov Chain Monte Carlo method, was used to sample the posterior
      probability density. The sample mean was regarded as an evaluation of the
      permittivity distribution. The results of simulation imaging with "blocky"
      objects showed that this set of methods made good use of information and had the
      advantages of feasibility and very strong anti-noise ability. In addition,it is
      capable of describing (definite or indefinite) prior information in a convenient
      and controllable way, as well as capable of giving the "complete" solution, i.e.,
      the occurrence probability of every permittivity distribution.

PMID- 16422078
TI  - [The effect of extracellular perfusion on dielectric spectroscopy of skeletal
      muscle cells].
AB  - The dielectric spectroscopy of the skeletal muscle cells is approached by
      extracellular perfusion, using curve fitting and numerical calculation with
      nonlinear Cole-Cole equation, and the dielectric parameter of skeletal muscle
      cells is compared after perfusion, The results show: (1) the permittivy at low
      frequency (epsilon1) and the conductivity at hight frequency (kappa(h)) reduces
      in keeping with extracellular perfusate; (2) the effect of extracellular
      perfusion on the characteristic frequency (f(c1),f(c2)) is small; (3) the
      extracellular perfusion mostly influences the peaks of deltaepsilon" and tgdelta
      for the skeletal muscle cells.

PMID- 16422079
TI  - [Tongue image color recognition in traditional Chinese medicine].
AB  - The problem of color recognition of substances and coats in tongue images was
      decomposed into two steps, i. e. region separation and color recognition. In the
      first step, a new method based on the JSEG and the k-NN algorithms was proposed
      to separate coats and substances, where a prior template and some standard color
      patches were designed to assist the classification. Color recognition in a fine
      scale was carried out by the nearest neighbour method on the basis of the first
      step. The experiments showed the method proposed in this paper was simple and
      highly robust, and can be applied to tongue characterization effectively. In
      addition, the two important preprocessing algorithms namely color calibration and
      segmentation of tongue images were improved to obtain better results than the
      former.

PMID- 16422080
TI  - [Numerical simulation of the relationship between blood pressure and blood stream
      of arteries].
AB  - The quantitative relationship between blood pressure and blood stream of
      arteries, which is delineated by hemodynamics, is rather complex to understand
      and analyze mathematically. An equivalent simulated mathematical model was
      utilized to numerically describe this sort of relationship. The physiological
      essence of layered flowage inside the artery was opened out. The numerical
      simulation was accomplished using several sets of real parameters. Some important
      conclusions about quantitative relationship of the layered flowage were drawn
      through the simulation results. The research results presented in this paper have
      important reference value in respect of quantitative research of circulation
      physiology and clinical diagnosis and analysis of some illness within circulation
      system.

PMID- 16422081
TI  - [Auto sleep staging and sleep quality estimation based on BP neural network].
AB  - To estimate the sleep quality, a 3-layer BP neural network was studied. The EEG
      complexity and the power spectrum of sleep-multigraph served as the input vector
      of the network . All-night sleep-stage scoring was performed. Then several
      parameters (sleep period, shallow sleep period, deep sleep period, REM period,
      ratio of the wakeful period and sleep one) were defined to estimate the sleep
      quality. The experiments revealed that the estimated sleep condition was the same
      as the subjects' impression. The data on six cases of all-night sleep show that
      this method is available to estimate the sleep quality.

PMID- 16422083
TI  - [Study of fluoroscopic triggering technique in 3D-dynamic contrast enhancement
      magnetic resonance angiography].
AB  - In the examination of 3D DCE-MRA, it is the key of success or failure to measure
      and compute the delaying scan time accurately. Now, the timing technique used
      widely in clinic is test injection bolus, which is limited by inadequate
      perfectibility, limited spatial resolution and technique complexity. In this
      article is presented a technique in which contrast arrival is detected in the
      targeted vasculature in real time using MR fluoroscopy. Upon detection the
      operator triggers a 3D MR angiographic acquisition which uses an elliptical
      centric view order. It is shown that the view order intrinsically provides a high
      degree of venous suppression, a high degree of immunity to motion effects and a
      high degree of spatial resolution. The reliability of fluoroscopic triggering in
      bolus detection is shown to be over 95%. The technique provides high quality
      contrast-enhanced MR angiograms for many vascular regions.

PMID- 16422082
TI  - [Image segmentation in tongue characterization].
AB  - Tongue diagnosis is one of the essential methods of traditional Chinese medical
      diagnosis. The accuracy of tongue diagnosis can be improved by tongue
      characterization. Tongue area segmentation and homogeneous regions segmentation
      in tongue are important contents of preprocess of tongue image. An algorithm
      based on edge detection and Gradient vector flow (GVF) active contour for tongue
      area segmentation and another algorithm based on unsupervised segmentation of
      color-texture for homogeneous regions segmentation in tongue were presented.
      Totally about 1500 tongue images were collected. Results of tongue area
      segmentation achieved accuracy rate of 94.3% and results of homogeneous regions
      segmentation in tongue were approved by traditional Chinese medical experts. The
      experiments results show robustness of the algorithms. This work establishes
      solid foundation for feature selecting of Tongue diagnosis.

PMID- 16422084
TI  - [Study on technique of thermal imaging and soft-sensing].
AB  - The differences of body surface temperature reflect the changes of the status of
      body tissues. In this regard, detecting and forecasting the changes of the
      surface temperature is the objective of the technique of medical thermal
      diagnosis, and how to diagnose the disease earlier with the use of thermal images
      is a common problem in the field of medical diagnostics and biological
      engineering. The authors put forward that utilizing the soft-sensing techniques
      in the field of engineering will be a good solution.

PMID- 16422085
TI  - [Relationship between age and the energy density distribution of fundamental and
      harmonic frequency component in electrocardiogram energy spectrum].
AB  - In a least square method, an exponential function fits the energy density
      distribution of fundamental and harmonic frequency component in a long-term ECG
      energy spectrum. A distributing index of the function was used to quantify
      divergence and convergence degree of energy density. The function fits locally
      the ECG energy spectrum data that were collected from the young (21-34 yr) group
      and elderly (68-81 yr) group rigorously energy density ratio of the harmonic to
      fundamental frequency component and recognizability number of harmonic frequency
      component were significantly less in the young group than in the elderly group (P
      < 0.01), the center frequency f0 and energy density at center frequency f0 did
      not differ between the two age groups. These data indicate that the
      characteristic parameter values presented in this study can serve as a new
      measurement of heart rate fluctuations.

PMID- 16422086
TI  - [The design of an instrument furnished with hydrogen clearance technique for
      measuring local blood-flow and the microcomputer analysis curve on hydrogen
      clearance].
AB  - A new instrument, furnished with hydrogen clearance technique for measuring local
      blood-flow, was designed by use of new electronic components and a
      microcontroller. The corresponding program was developed. The curve of hydrogen
      clearance was sampled automatically by microcomputer, fitted into an exponential
      function by least square method, and then the local blood-flow was calculated.
      The cerebral blood-flow in the rat's striatum had been measured using the system.
      The fitted curve corresponds with the curve of hydrogen clearance and the
      obtained parameter was correct. The design of the instrument was reasonable. It
      can work reliably and stably. The calculated results are more accurate and they
      can be acquired more quickly, because the curve of hydrogen clearance is
      automatically sampled and analyzed by the microcomputer.

PMID- 16422087
TI  - [Watershed-based segmentation of histiocytic images].
AB  - The task of segmenting histiocyte is a crucial step in the analysis of
      histiocytic images which is an important application of computer vision to
      histopathology. The algorithm presented in this article was composed of two
      steps: (1) the morph-based preprocessing; (2) the ameliorated watershed method.
      In the first step, the difference between histiocytes was magnified in order to
      increase the visibility from the view of the computer vision, and then the
      ameliorated terrace-flooding-simulated watershed method was used to achieve the
      segmentation of histiocytic images in the second step. To test the performance of
      the algorithm, different samples of visual quality were tested and the result
      figures proved successful.

PMID- 16422088
TI  - [Studying psychology test EEG based on information transmission of cerebral
      cortex].
AB  - 23 subjects' 8-lead (Fp1, Fp2, Cp3, Cp4, T7, T8, P7, P8) electroencephalogram
      (EEG) was recorded when they were doing mental arithmetic at four different
      levels. We calculated the information transmission time series in human cerebral
      cortex basing on EEG, and the Lempel-Ziv complexity and C1C2 complexity of these
      time series. When 20 subjects were doing the most difficult mental arithmetic,
      the information transmission series between lead at left-brain (Cp3, T7, P7) and
      other leads was of more complexity than others; a light "cross" could be seen
      after the information transmission matrix was converted to image; when complexity
      was calculated, the difference was more significant by use of C1 complexity than
      by other complexity measures.

PMID- 16422089
TI  - [A study on technology to identify human beings or animals in life-detector based
      on radar].
AB  - To determine whether a living object is human being or animal by detecting the
      respiration signal using the life-detector based on radar to penetrate the
      building or debris. To fully utilize the nonstationary character of the
      respiration signal, short time Fourier transform (STFT) is employed to get the
      signal's time-frequency representation. Singular value decomposition (SVD) is
      then used in the spectrogram to extract feature vector for pattern
      identification. Human beings and animals can be identified from the respiration
      sensed by the life-detector based on radar. Experimental results show that the
      method based on STFT and SVD is stable and efficient to differ from the human
      being and animal.

PMID- 16422090
TI  - [Effect of low stress environment on bone density and geome-morphology of rat
      femur].
AB  - 6-week old rats were subjected to sciatic nerve resection and the right hindlimbs
      were then under a low stress environment. Bone mineral density (BMD) of different
      regions and geome-morphological parameters of femurs were measured. The results
      showed that the increase in the diameter, subperiosteal area and bone mineral
      density of femurs were suppressed obviously under low stress environment. But the
      sensitivity of BMD of different regions of the femur to the low stress
      environment was different. The suppression of the increase in femoral BMD was
      composed of an early impairment in the gain of BMD at the femoral metaphysis,
      which is rich in trabecular bone, and a sustained reduction in the gain of BMD at
      the femoral diaphysis, which is rich in cortical bone. The results of geome
      morphology suggested that the early reduction in the increase of BMD at the
      metaphysis was due to an enhancement of bone resorption, whereas the suppression
      of gain in cortical bone mass and size is the result of a sustained reduction of
      periosteal bone formation.

PMID- 16422091
TI  - [Effects of the PEMFs of different intensity on BMD and biomechanical properties
      of rabbits' femur].
AB  - The effects of the pulsed electromagnetic fields (PEMFs) of different intensity
      on bone mineral density (BMD) and biomechanical properties of rabbits' femur had
      been studied. Twenty-seven female white big ear rabbits were randomly divided
      into three groups. The magnetic groups were fed in 15 Hz PEMFs, which pulse
      duration was set to be 5 ms (6 h x d(-1)), the magnetic intensity was 10 x 10(-4)
      T and the other was 20 x 10(-4) T. Control group were just fed in coils, and the
      instrument of PEMFs was powered off. After six weeks, by examine BMD and
      biomechanical properties of the rabbits' femur, the effects of these PEMFs were
      studied. Compared with control group, the values of BMD, maximum load and
      structural rigidity of magnetic group were significantly increased (P < 0.05). In
      addition, there was significant increase in values of BMD and structural rigidity
      in group 10 x 10(-4) T in comparison with group 20 x 10(-4) T (P < 0.05). PEMFs
      is effective in improving BMD and biomechanical properties. The experiment
      indicated that there was evident "window-effect" during the treatment by PEMFs.
      It is favorable to the treatment and prevention of osteoporosis.

PMID- 16422092
TI  - [Study on chitosan-DNA nanoparticles as gene carriers].
AB  - The preparation and cell transfection of chitosan-DNA nanoparticles were studied.
      The TFPI (tissue factor pathway inhibitor) or EGFP (enhanced green fluorescent
      protein) plasmid DNA was encapsulated with chitosan to form gene nanoparticles.
      The results with TEM showed that the nanoparticles were of sphere shape. The mean
      diameter of the nanoparticles was 149 nm and the diameter ranged from 80-250 nm,
      which were measured by the photo related spectrometry (PCS). The encapsulation
      efficiency of DNA was 96% +/- 1.38% and the DNA content in the nanoparticles was
      37% +/- 3.0%. The encapsulated DNA could be protected from the degradation by
      DNase I. The transfection efficiency of chitosan nanoparticles were about
      equivalent to that of the LipofectAMINETM reagent. Our results also showed that
      chitosan nanoparticles were nontoxic to cultured cells.

PMID- 16422093
TI  - [Experimental observation on the effects of different chitosan on preventing
      peritoneal adhesion in rats].
AB  - This experiment was designed to investigate the effects of different chitosan on
      preventing peritoneal adhesion in rats. 240 SD rats were divided into 2
      jumbogroups: jumbogroup A (144 rats) treated with chitosan gel and jumbogroup B
      (96 rats) with chitosan/gelatin mixed film. In jumbogroup A, 144 rats were
      randomly divided into 3 groups further, and different methods were used to induce
      peritoneal adhesions in each group while in the experiment group the wounded
      processus vermiformis was coated with chitosan gel before it was put back into
      the abdominal cavity. In jumpbogroup B, 96 rats were randomly divided into 4
      groups (24 each) after surgical induction of perioneal adhesions; group B1 served
      as control group while in groups B2, B3 and B4, pure chitosan film and the
      chitosan film containing gelatin were respectively spread over the surface of the
      wounded. 2 and 4 weeks after surgical induction, exploratory laparatomy was
      performed on the rats to evaluate peritoneal adhesion, and the adhesive tissues
      were examined histopathologically. The results show that chitosan gel has perfect
      protective efficacy against traumatic or ischemic peritoneal adhesion, but pure
      chitosan film and the film chitosan containing gelatin could exacerbate
      peritoneal adhesion further.

PMID- 16422094
TI  - [A methodological study on testing the elastic modulus of soft bio
      anthropomorphic materials].
AB  - It is difficult to test the elastic modulus of the soft bio-anthropomorphic
      materials by using the general stretch-strain test method. With the equipment for
      a hardness testing system of bio-anthropomorphic materials and millesimal gauge,
      we introduce in this paper a compress-strain test method and carry out the
      related test-data curve-fitness. The test results indicate that this kind of
      method can be adopted in testing the elastic modulus of the soft bio
      anthropomorphic materials and help to compare and distinguish the biomechanics
      equivalent between the tissues.

PMID- 16422095
TI  - [Effect of polymeric scaffolds on attachment and growth of bone marrow
      mesenchymal stem cells].
AB  - To investigate the effect of three kinds of polymeric scaffolds on attachment,
      proliferation and differentiation of bone marrow mesenchymal stem cells, the
      cells were different polymeric scaffolds of PLA-PEG, PLA, PLGA, respectively. The
      proliferation of cell was evaluated by cell count; the attachment and morphology
      of BMSCs were observed by SEM; and differentiation was detected by alkaline
      phosphatase activity, fluorescence, and RT-PCR methods. Results showed that the
      cells in PLGA group spread better among BMSCs adhered to the three polymeric
      scaffolds. The activity of ALP was detected after 3 days culture in these three
      groups. There were no significant differences between PLA-PEG and PLGA groups,
      but the activity of ALP was higher than PLA group. The gene expressions of
      osteocalicin and collagen I were also observed in the early culture time. Calcium
      nodes formation in these polymeric scaffolds were detected. BMSC spreading first,
      then overlapping growth and secretion of matrix around the bottom and surface of
      scaffolds were observed through SEM. In summary, PLA-PEG and PLGA are better
      polymeric scaffolds for the bone tissue engineering, compared with PLA.

PMID- 16422096
TI  - [Effect of erosion on strength of dental infiltrated Al2O3 ceramics].
AB  - The objective of the research is to investigate the elements of routine sandblast
      technique on the evolution of bending strength of dental infiltrated Al2O3
      ceramics and the underlying erosion mechanism. The plane specimens of an
      infiltrated ceramic were manufactured, polished and then tested under the
      modified pen-like sandblasting apparatus (90 degrees erosive angle and 10 mm
      sandblasting distance), with different grit sizes, working pressure and disposing
      time. Half of samples were selected randomly and sintered subsequently with
      Vitadur alpha veneering porcelain. Before and after sintering, the three-point
      bending strengths was measured, and the surfaces of dental porcelain were
      observed with SEM and LCSM. The bending strength of ceramics decreased
      significantly after sandblast as compared with that of empty control group. After
      the procedure of sintering the veneering porcelain, the descending evolution of
      bending strength slowed down. Under the present manufacturing conditions, grit
      size effect is prominent among those correlative elements of sand grit size,
      working pressure and disposing time. And fatigue cracking characterizes the
      mechanism of erosion of dental infiltrated Al2O3 ceramics.

PMID- 16422097
TI  - [The effect of technological parameters of wide-band laser cladding on
      microstructure and sinterability of gradient bioceramics composite coating].
AB  - The gradient bioceramics coating was prepared on the surface of Ti-6Al-4V alloy
      by using wide-band laser cladding. And the effect of technological parameters of
      wide-band laser cladding on microstructure and sinterability of gradient
      bioceramics composite coating was studied. The experimental results indicated
      that in the circumstances of size of laser doze D and scanning velocity V being
      fixed, with the increasement of power P, the density of microstructure in
      bioceramics coating gradually degraded; with the increasement of power P, the
      pore rate of bioceramics gradually became high. While P = 2.3 KW, the bioceramics
      coating with dense structure and lower pore rate (5.11%) was obtained; while P =
      2.9 KW, the bioceramics coating with disappointing density was formed and its
      pore rate was up to 21.32%. The microhardness of bioceramics coating demonstrated
      that while P = 2.3 KW, the largest value of microhardness of bioceramics coating
      was 1100 HV. Under the condition of our research work, the optimum technological
      parameters for preparing gradient bioceramics coating by wide-band laser cladding
      are: P = 2.3 KW, V = 145 mm/min, D = 16 mm x 2 mm.

PMID- 16422098
TI  - [Research on the modeling of biological valves poppet].
AB  - In this paper are described the construction of biological valves poppet and the
      establishment of mathematical model according to cardiac valves hydrokinetics and
      the theory of membrane. Finite elements of biological valves leaflets connected
      with biological valves poppet are analyzed. The method of constructing geometric
      model is reasonable. CAD of biological valves poppet is realized by structured
      programming and parameterization.

PMID- 16422099
TI  - [Mechanical strain of different waveform and frequency inhibits proliferation of
      lung adenocarcinoma cell in vitro].
AB  - The effects of waveform and frequency on proliferation of human lung
      adenocarcinoma cell line A549 were studied by FX-4000 strain unit . The results
      showed that cellular proliferation index (PI) reduced significantly in squarewave
      group when compared with the control after A549 cells were subjected to collagen
      I 0-25% elongation at frequency 20 cycles/min, 40 cycles/min and 60 cycles/min
      for 2h. The PI showed no distinct difference in trianglewave group. The PI
      increased in heartwave group. These data indicate that A549 cells do respond to
      physiological strain in vitro. The effects of squarewave and 60 cycles/min
      tension may be optimal for inhibiting the proliferation of A549 cells. To select
      appropriate waveform and frequency will be of paramount importance to inhibiting
      proliferation of A549 cells.

PMID- 16422100
TI  - [Immunogenicity of acellular bovine pericardium in vivo].
AB  - To investigate the feasibility of making up bovine pericardium into scaffolds for
      tissue engineering valve, it was decellularized by 0.5% trypsin incubation for
      three hours. The rats were divided into fresh bovine group, acellular pericardium
      group and control group, and OD value of rat anti-bovine IgG was measured. Serum
      levels of IgG showed no difference among the three groups on the 7th day
      postoperatively (P > 0.05). The OD values of IgG at other time-points displayed
      distinct difference among the three groups (P < 0.05). Fresh bovine pericardium
      group produced more IgG than acellular bovine pericardium group did at the same
      time-point. The IgG level of fresh bovine pericardium group reached the peak
      postoperatively, but in acellular bovine pericardium group its peak value
      appeared on the 30th day postoperatively. Histological examination demonstrated
      that the bovine pericardium was thoroughly decellularized, the fibrous structure
      was slightly loose, but remained essentially intact. These results indicate that
      the acellularization procedure can result in a complete removal of cells and
      decrease of immunogenicity.

PMID- 16422101
TI  - [Study on the conditions of high density fermentation for the engineering
      bacterial strain with RGD spider silk protein gene].
AB  - Spider silk becomes the protein fibroin with excellent character in the natural
      world because of its unique mechanical properties. The genetic engineering
      technique is an effective method to procure the spider silk protein. In order to
      obtain RGD-spider silk protein gene recombinant engineering strain pNSR-16 on a
      regular scale, we determine the optimal conditions of the growth and expression
      of pNSR-16 through culture in laboratory, and based on these, study the fed-batch
      high density culture. We control the flow of carbon-nitrogen, the dissolved
      oxygen concentration and the cell specific growth rate, which make the final cell
      density and concentration of recombinant protein of total protein arrive at OD600
      57.15 and 20.8%, respectively.

PMID- 16422102
TI  - [Gene transfer by a novel nonviral vector polyethylenimine].
AB  - This study inquired about the influences on the gene delivery efficiency of
      polyethylenimine. pSVbeta plasmids were transferred into COS-7 and NIH3T3 cells
      with polyethylenimine. Influences of plasmids factor, albumin, serum, cell
      density, operation methods and polyethylenimine/DNA preserve factors on
      transfection efficiency were investigated. Inhibitors of biological activities in
      plasmids could be removed by ultrafiltration with cutoff molecular weight of 3000
      or 10000. Linear plasmids lowered transfection efficiency. Serum and albumin in
      the culture medium decreased the transfection efficiency of polyethylenimine/DNA.
      Cell density was associated with PEI/DNA transfection efficiency. Incubation of
      PEI/DNA complexes with the cells for 8 h and then aspiration for removal of the
      complexes could obtain an optimal transfection effect. Freezing of PEI/DNA
      complexes significantly decreased transfection efficiency. In conclusion,
      polyethylenimine could obtain optimal and reduplicate transfection results by
      controlling related factors.

PMID- 16422103
TI  - [Research and development of a piezoelectric immunosensor for detecting Treponema
      pallidum].
AB  - We utilized polyethylenimine (PEI) and Glu solution to immobilize the antibody of
      Treponema Pallidum on the silver electrode of piezoelectric quartz crystal and
      detect the standard antigen solution at different concentration. The antibody
      keeps the intrinsic Y type molecular structure revealed by AFM. The resonant
      range of the sensor is between 5 x 10(-5) - 1.25 x 10(-4) g/mL and the
      correlation coefficient is 0.9976, the optimal resonance pH is 7.5. We found the
      sensor having good selectivity in comparison with the method using BSA. At last,
      a discussion on the reproducibility of the sensor is presented.

PMID- 16422104
TI  - [Building immune microsphere against tumor necrosis factor-alpha (TNF-alpha)].
AB  - We have constructed the immune microsphere against tumor necrosis factor-alpha
      (TNF-alpha) prospectively, hoping to establish the experiment groundwork in more
      researches which could be used in specific elimination of the TNF-alpha by blood
      purification method for the future. The recombinant human tumor necrosis factor
      alpha monoclonal antibody (rHTNF-alpha McAb) was wrapped on the polystyrene
      microsphere (PSM) carrier connecting poly-L-lysine (PLL) beforehand. They were
      earmarked by the fluorescein isothiocyanate (FITC) respectively. The packing
      conditions were examined using the inversted and fluorescence microscopes and the
      spectrophotometer. The results showed that the best conditions for wrapping were
      20 degrees C, pH9.5 and 60 minutes. The PLL content was not changed in the
      washing fluid after coating, which indicated the wrapping was quite firm. At the
      same temperature and same coating time, the rHTNF-alpha McAb coated on the PLL
      was obviously substantial when the concentration of glutaraldehyde solution was
      0.2%. The findings demonstrated that the built immune microsphers can be used as
      a novel adsorption material. This method is simple and economic, and it offers a
      new approach to the related studies.

PMID- 16422105
TI  - [In vitro study of the directed inducing cartilage cells from rat bone
      mesenchymal stem cells on scaffolds].
AB  - This study was conducted to assess the cell proliferation and cell cycle of the
      directed inducing cartilage cells from rat bone mesenchymal stem cells on
      collagen sponge and compare the results with those of the plane inducing
      cartilage cells. The MSCs were isolated from rat bone marrow by density gradient
      centrifuge and adhesive property, and then were induced into chondrogenic
      differentiation by adding transforming growth factor-beta1 (TGF-beta1),
      dexamethasone, transferring and insulin on collage sponge and plane condition.
      Immunohistochemistry was applied to detect the expression of collagen type II on
      the scaffolds and plane conditions. The cell proliferation and cell cycle on
      different conditions were detected with MTT automated colormetric microassay and
      flow cytometry. The differentiation of MSCs toward chondrogenic phenotype was
      verified by the positive result of collagen type II on the scaffolds and plane
      condition. The cell viability in scaffolds was better than that in plane
      conditions. The S phase and G2 phase were 30 percent in whole cell cycle on the
      scaffold, which was different from that of the control groups. The method of
      using the Using directed inducing cartilage from bone MSCs combined with collage
      sponge to construct tissue-engineered cartilage is feasible; it is better than
      the method of plane directed inducing.

PMID- 16422106
TI  - [Effect of isorhmnetin on circadian rhythms of DNA synthesis and expression of c
      myc gene in Eca-109 cells of human oesophageal cancer].
AB  - This study was focused on the circadian rhythms of DNA synthesis and the
      expression of c-myc gene in untreated and treated Eca-109 cells in human
      oesophageal cancer with isorhmnetin. The circadian rhythms of 3H-TdR
      incorporation and expression of c-myc gene in untreated and treated Eca-109 cells
      were measured by 3H-thymidine uptake assay and flow cytometry. The data collected
      were analyzed by ANOVA and Cosinor method. DNA synthesis and expression of c-myc
      gene in untreated group varied according to circadian time with statistical
      significance, the distribution curves of both DNA synthesis and the expression
      level of c-myc were fit for cosinor changes. The circadian rhythms of DNA
      synthesis and circadian parameters of c-myc expression in treated Eca-109 cells
      changed. The circadian parameters of DNA synthesis and expression level of c-myc
      varied after treatment by isorhmnetin. The effects of isorhmnetin on cell
      proliferation and c-myc expression reached the highest level from 20: 00 to 0:
      00. The results provide a guidance for instituting the chemotherapy and
      chronotherapy of human tumors, when isorhmnetin is for use as anti-cancer agent.

PMID- 16422107
TI  - [Experimental study of colorectal cancerous autofluorescent spectra induced by
      laser].
AB  - The researches reported in this article are focused on the autofluorescent signal
      collection of colorectal tissues by laser induced autofluorescent diagnostic
      system, and on the signal processing by power spectra and networks methods,
      Pretty good clinical diagnostic sensitivity and specificity are acquired. These
      may serve as a foundation on which to develop a system for diagnosis of colorecal
      cancer.

PMID- 16422108
TI  - [Differentiation of bone marrow mesenchymal stem cells into hepatocytes in
      hepatectomized mouse].
AB  - CD44+ CD29+ and CD44- CD29+ bone marrow mesenchymal stem cells (BMSCs) were
      isolated from bone marrow of BALB/C male donor mouse by adherence selecting in
      DMEM media with low glucose and 20% fetal bovine serum. Then P5 cells were
      injected into the liver remnants of hepatectomined female mouse. Simultaneous
      assays were performed on the injected liver lobe and other liver lobe for
      detecting the Y-chromosome by fluorescence in situ hybridization and for
      defecting the albumin or cytokeratin 18 (CK18) by fluorescence immunoassays. Both
      Y chromosome and albumin (or CK18) positive cell could be detected at 5 days and
      14 days after transplantation. At 14 days after transplantation, the liver weight
      in transplanted mouse was higher than that in model mouse. These results suggest
      that BMSCs could be induced to differentiate into hepatocytes and participate in
      the regeneration of liver.

PMID- 16422109
TI  - [Phagocytic function of macrophage after partial splenectomy of rabbits using
      microwave tissue coagulation].
AB  - The immune function of spleen after partial splenectomy (PSM) of rabbits was
      stuided using microwave tissue coagulation (MTC). Streptococcus pneumoniae
      suspension was injected into the ear veins of rabbits 4 weeks after they were
      subjected to partial splenectomy using microwave tissue coagulation (PSM) group
      and to sham operation (SO groups), respectively. India ink was given via portal
      vein. Residual spleen were resected and microscopic examinations were performed
      on spleen slices stained using HE to compare phagocytic functions of macrophage.
      Gradings of phagocytic function in macrophage were of no significant difference
      between PSM and SO groups (P > 0.05). Weights of spleens showed no significant
      difference between the two groups (P > 0.05). The phagocytic function of
      macrophage after PSM can be preserved well. The result of this experiment implies
      that splenic salvage using MTC is a clinically applicable method.

PMID- 16422110
TI  - [Construction of fusion expression vector of human-derived neurotrophin-6 gene
      encoding mature peptide and purification of its expressed product].
AB  - To get the mature peptide of human-derived neurotrophin-6 (NT-6), NT-6 gene
      encoding mature peptide was amplified by PCR, using the NT-6 cDNA that had been
      cloned as templet. The gene encoding mature peptide of NT-6 gene was cloned into
      pGEX1-lambdaT plasmid to construct the fusion expression vector. Expression of
      fusion protein in Escherichia coli was defected after induction by isopropyl beta
      D-thiogalactoside(IPTG). The mature peptide of NT-6 was collected with GST fusion
      protein purifying kit. It was shown that a fragment of 460bp was gained by PCR.
      With the techniques of double-cleave and electrophoresis, the recombinant vector
      was identified as pGEX1-NT-6. The recombinant vector pGEX1-NT-6 transformed
      Escherichia coli expressed fusion protein of 41KD after induction by IPTG.
      Cleaved by thrombin, the mature peptide of NT-6 was obtained; its molecular
      weight was about 15KD. The cloning and expression of human-derived NT-6 gene
      encoding mature protein has provided a basis for further studies on the function
      and clinical application of NT-6.

PMID- 16422111
TI  - [Electrospinning and morphology of ultrafine poly (D, L-lactide) fibers].
AB  - Ultrafine poly (D, L-lactide) (PLA) fibers with diameter less than 200 nm
      produced by electrospinning were studied to obtain tissue restoration resembling
      extracellular matrix. Scanning electron microscopy was used to observe the fiber
      morphology. Results showed that the solvent was the critical factor to determine
      the formation of the electrospun PLA fibers. Compared with acetone, N,N
      dimethylformamide (DMF) was a better solvent for PLA to electrospin. Entrance of
      an organic salt, triethylbenzylammonium chlorate, led to a great increase of the
      conductivity of PLA/DMF solutions, so that the average fiber diameter of the
      electrospun PLA fibers decreased dramatically from 500 nm to 100-200 nm. The
      addition of surfactant, Span-80, did not improve the fiber morphology but formed
      beaded fiber web.

PMID- 16422112
TI  - [Intelligent peritoneal dialysis system for the treatment of renal failure].
AB  - Peritoneal dialysis is an important approach to the treatment of renal failure
      diseases such as acute renal failure, chronic renal failure and uremia. In this
      paper are presented the application of the multifunction squirm pump developed by
      authors, the use of PLC and single-chip to control harmonically, and the
      instituition of full automatic dialysis therapy. Man-machine interface with
      integrative touch liquid crystal display is adopted in the system, and Chinese
      interface is used to display and operate so that user can manipulate it in a
      guiding way. Hence, the whole process is simple and clear. At the same time, it
      is very easy to set dialysis parameters suited for medical treatment demands of
      all kinds of patients. Through squirm pump, electric valve, electronic weighing
      system and electrical heating system, the accurate control of input and output
      dialysis volumes, flow velocities, temperature, and other parameters are achieved
      and automatic alarm function is also implemented. Meanwhile, particular
      intelligent card system that can access automatically the user's treatment
      information is syncretized, which is convenient for doctor to make a diagnosis
      and give treatment or to carry out remote treatment. This system plays an
      important role in the improvement of peritoneal dialysis technique for renal
      failure treatment and clinical implementation.

PMID- 16422114
TI  - [A method for automatic selection of optimal standard hip stems].
AB  - In a hip replacement case when a standard hip stem is chosen, it is rough to
      select hip stems before operation, thus some stand-up standard hip stems should
      be prepared. The operation time is usually prolonged. In order to solve this
      problem, this paper presents a method to automatically select optimal standard
      hip stems by computers. Femoral anatomical data of a patient are acquired from X
      ray films. Based on these anatomical data and a database of average cross
      sections in proximal femurs, proximal femur of the patient can be reconstructed.
      This proximal femur model makes it possible to optimally select a standard hip
      stem. Theory analyses indicate that the method, presented in this paper, is
      practicable.

PMID- 16422113
TI  - [A hydrostatic compression device capable of generating both intermittent
      compressive forces and continuous compressive forces].
AB  - A hydrostatic compression device has been designed to study the effects of
      intermittent or continuous compressive forces on cells by trying to mimic in vivo
      forces. The model system is composed of two pistons that deliver and release
      compressed air under control of a motor to form an enclosed tissue culture
      chamber housing numerous tissues culture dishes. The continuous compressive
      forces and intermittent compressive forces are within 100-300 KPa and 0-30 KPa
      respectively. The compressive force is uniform in the system and can also result
      in the generation of shear forces along the interface between the cells and
      culture substratum, so the hydrostatic compression device can be used to study
      the characteristics of in vitro cells loading models.

PMID- 16422116
TI  - [A new method for measuring linearity of physiological instrumentation].
AB  - Based on theoretic analysis, a new method for measuring linearity of
      physiological instrument and its inner unit circuits is provided. In this method,
      the sawtooth wave signal, which includes a base wave and its odd-even times
      harmonic waves, is used to act as input signal, then the linearity of
      physiological instrument and its inner unit circuits can be measured by analyzing
      the shape and frequency property of the output signal. The results of experiment
      show this method is quick and convenient for measuring the linearity of
      physiological instrument and its inner unit circuits.

PMID- 16422115
TI  - [Application of high frequency component in classification of different mental
      tasks].
AB  - Electroencephalogram (EEG) signals of different mental tasks were preprocessed
      using Independent Component Analysis (ICA). Auto-Regressive (AR) model was used
      to extract the feature, and Back-Propagation (BP) network as the classifier. When
      features were extracted from 20-100 Hz high frequency range, the classification
      accuracy was the same as that taken from the whole frequency range and was more
      higher than the result of 2-35 Hz normal EEG rhythm. The explanation of this
      phenomenon is: brain displays different rhythm assimilation during different
      mental task under the effect of 60 Hz power frequency, so the high frequency
      components of EEG include more mental modulated information which is useful for
      improving the classification accuracy. The result presents a new evidence for the
      brain rhythm assimilation phenomenon and gives a novel feature extraction method
      for realizing high accuracy real-time BCI based on mental task.

PMID- 16422117
TI  - [Automated anesthesia record system].
AB  - Based on Client/Server architecture, a software of automated anesthesia record
      system running under Windows operation system and networks has been developed and
      programmed with Microsoft Visual C++ 6.0, Visual Basic 6.0 and SQL Server. The
      system can deal with patient's information throughout the anesthesia. It can
      collect and integrate the data from several kinds of medical equipment such as
      monitor, infusion pump and anesthesia machine automatically and real-time. After
      that, the system presents the anesthesia sheets automatically. The record system
      makes the anesthesia record more accurate and integral and can raise the
      anesthesiologist's working efficiency.

PMID- 16422118
TI  - [Developments in understanding of interactions between blood and biomaterials at
      molecular and cellular levels].
AB  - Blood compatibility is one of the most important factors for biomaterials applied
      in blood-contacting environment, which is determined by a series of complicated
      interactions of biomaterials surfaces with both soluble and cellular components
      in blood. As the development of molecular biology technology and emergence of new
      characterization methods for changes of protein conformation structure and
      function, more and more researchers are making intensive efforts to understand
      hemocompatibility of biomaterials at molecular and cellular levels. In this
      paper, developments in understanding of interactions between blood and materials
      surfaces, especially the changes of plasma protein conformation structure and
      activation of platelets induced by biomaterials surfaces, are reviewed.

PMID- 16422120
TI  - [Recommendations for mitral regurgtitation with Doppler echocardiography].
AB  - Mitral regurgitation is one of the most serious heart diseases. With the
      development of up-to-date medical techniques, the ratio of successful operations
      in valvular repair and valvular replacement has been largely improved.
      Examinations before operation become extremely crucial. Accurate method is
      required in assessing the degree of mitral regurgitation to set down the
      corresponding treatment method. This paper reviews the evaluation methods of
      mitral valvular regurgitation provided in these years and presents comments on
      the application areas as well as the merits and disadvantages of those methods.
      Finally, the prospect of the method based on three-dimensional Doppler
      ultrasonographic imaging on mitral regurgitation is discussed.

PMID- 16422119
TI  - [Environmental stimuli-sensitive biodegradable drug delivery systems].
AB  - Environmental stimuli-sensitive biodegradable drug delivery systems are drawing
      more and more attentions because of their advantages such as smart properties,
      high efficiency and easy-to-handle properties. On the basis of a large quantity
      of references on this topic, a review has been made on the developments of the
      thermosensitive and pH-sensitive intelligent polymeric systems for drug delivery.

PMID- 16422121
TI  - [Molecular mechanism of bone absorption in osteoclast].
AB  - The physiological reconstruction of bone is strictly dependent on bone
      resorption. Bone resorption is believed to be a complicated molecular reaction
      process that occurs in the microcircumstance of bone tissue. A lot of enzymes and
      factors take part in this process, yet there are not enough data with reference
      to the activation of osteoclast, resorption of bone matrix, regulation of bone
      resorption. In this paper we review the importance of matrix metalloproteinases
      (MMPs) in transfer of osteoclast and degradation of bone matrix, and the function
      of receptor activator of NF-kappaB-ligand (RANKL) and osteoprotegerin (OPG) in
      regulation of bone resorption.

PMID- 16422122
TI  - [Advance in researches on materials for abdominal wall defect].
AB  - How to succeed in repairing an immense abdominal wall defect is often a perplexed
      question for surgeons. Finding perfect substitute material, therefore, is of
      great importance. The materials in this regard are often divided into two
      categories: biomaterial and non-boimaterial. The former has excellent mechanics
      properties while the latter possesses more favourable biocompatibility. The
      characteristics, clinical effects and advantages of biomaterials and non
      biomaterials for abdominal wall repair are reviewed.

PMID- 16422123
TI  - Long-term outcome after coronary angioplasty: where do we stand?

PMID- 16422124
TI  - Awareness, treatment and control of the metabolic syndrome and its components: a
      multicentre Greek study.
AB  - INTRODUCTION: There are no data concerning the degree of awareness, treatment and
      control of the metabolic syndrome (MetS) and its components or associated
      vascular risk in the general population. METHODS: A cross-sectional analysis was
      made of a representative sample of Greek adults (n=9669, 49% men and 51% women),
      living in urban, semi-urban and rural areas (55%, 23% and 22%, respectively). The
      National Cholesterol Education Program (NCEP-ATP III) and the International
      Diabetes Federation (IDF) definitions for the MetS were used. RESULTS: The age
      standardised prevalence of the MetS in the general population was 24.5% [95% CI
      23.4-25.7%] (n=2369). This was similar in men and women and increased with age.
      Among subjects with the NCEP MetS the prevalence of hypertension was 71%,
      elevated blood glucose 55%, low high-density lipoprotein cholesterol 58%, high
      triglycerides 63% and abdominal obesity 82%. Only one third of subjects were
      aware of the MetS component conditions, less than one quarter were on treatment,
      and very few (< or =10%) were controlled for MetS components. Awareness of MetS
      individual component conditions (e.g. arterial hypertension), and consequently
      effective control, was lower than that reported in other cohorts, including
      subjects without MetS. Only 5% of subjects were aware of MetS as an entity, 2%
      were treated for all component conditions and only 1% were controlled. Using the
      IDF definition, the prevalence of MetS was higher (43.4%) and awareness,
      treatment and control of MetS and its components were significantly lower.
      CONCLUSIONS: The prevalence of MetS is high in Greece but is not recognised among
      the general population. Therefore, treatment and control of MetS and component
      conditions are extremely low. If the situation does not improve soon, MetS will
      cause a further increase in the vascular disease epidemic in the years to come.
      This calls for urgent education of the public and the medical community.

PMID- 16422126
TI  - Association of impaired glucose tolerance with increased heart rate and
      subclinical inflammation.
AB  - INTRODUCTION: This study was designed to assess possible alterations in heart
      rate (HR), heart rate variability (HRV) and circulating serum levels of
      proinflammatory cytokines in patients with impaired glucose tolerance (IGT).
      METHODS: Forty-five patients, aged 34-68 years, with IGT were compared with 28
      age-matched healthy controls. Using a 24-hour ambulatory electrocardiogram, we
      calculated mean HR during daytime (HR-D), night-time (HR-N) and the entire 24
      hour period (HR-24h), as well as time domain HRV parameters. From blood samples
      interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-a) and its soluble
      receptor (sTNFRII) were also calculated by immunoassay. RESULTS: Patients showed
      higher mean HR compared to controls and significantly elevated circulating levels
      of TNF-a, sTNFRII, and IL-6. Pearson correlation analysis showed that TNF-a was
      positively correlated with mean HR-D (r: 0.304, p=0.042). IL-6 was also
      positively correlated with mean HR-24h (r: 0.299, p=0.046) and with mean HR-D (r:
      0.410, p=0.005). CONCLUSION: IGT patients have an increased HR and elevated
      cytokine levels. These changes could serve as an index of the primary
      atherosclerotic process.

PMID- 16422125
TI  - Registration of antithrombotic policy for the management of acute coronary
      syndromes in the Greek population.
AB  - INTRODUCTION: In this study an attempt was made for the first time in the Greek
      population to register the antithrombotic medication given to patients with acute
      coronary syndromes (ACS), both during their hospitalisation and on discharge.
      METHODS: The study was designed to include all patients with ACS in a total of 22
      hospitals in Athens and other parts of Greece. An analysis was made of
      differences in the administration of antithrombotic agents in relation to region,
      sex and age. RESULTS: From the data recorded it emerged that patients in Athenian
      hospitals more often receive aspirin and heparin than do those in other regions.
      Also, women with acute myocardial infarction are given aspirin and platelet
      glycoprotein IIb/IIIa inhibitors less frequently than men. In addition, elderly
      patients with non-Q infarction and unstable angina are treated less often with
      clopidogrel than are younger patients. CONCLUSIONS: A large number of patients
      with ACS do not receive antithrombotic medication in accordance with the
      guidelines. Furthermore, it appears that population groups who are considered to
      have higher risk and poorer prognosis, such as the elderly and women, are
      undertreated.

PMID- 16422127
TI  - Postoperative arrhythmias in tetralogy of Fallot.

PMID- 16422128
TI  - Aldosterone in heart and kidney diseases.

PMID- 16422129
TI  - The contribution of Doppler echocardiography to the assessment of left
      ventricular long axis function.

PMID- 16422130
TI  - Unexpected aortic dissection.

PMID- 16422131
TI  - Rheolytic thrombectomy combined with a protective filter and platelet
      glycoprotein IIb/IIIa receptor inhibitors in rescue angioplasty.
AB  - Rescue angioplasty is used in patients in whom thrombolysis has been
      unsuccessful, in order to achieve a better restoration of flow and to improve
      left ventricular function and the long term prognosis. However, patients who
      undergo rescue angioplasty have a higher rate of reocclusion of the vessel or
      distal embolism, resulting in increased mortality. Rheolytic thrombectomy, which
      reduces the quantity of thrombus and improves flow in the vessel, has been used
      successfully in such cases. We describe a case in which rheolytic thrombectomy
      was applied during late rescue angioplasty in order to achieve immediate
      restoration of flow in the vessel.

PMID- 16422132
TI  - Nonbacterial vegetations in a young patient with primary antiphospholipid
      syndrome.
AB  - The classical clinical picture of the antiphospholipid syndrome (APS) is
      characterized by venous and/or arterial thromboses, fetal losses and
      thrombocytopenia, in the presence of antiphospholipid antibodies (aPL). We
      present the case of a young male patient who suffered a transient ischemic
      cerebrovascular attack and whose cardiac investigation revealed a cardiac source
      of embolus, namely non-bacterial vegetations of the mitral valve. Laboratory
      testing confirmed the diagnosis of primary APS.

PMID- 16422133
TI  - Stent fracture and restenosis of a paclitaxel-eluting stent.
AB  - We describe the case of a patient with restenosis six months after stent
      implantation, at two points where stent fracture had occurred. Fracture is an
      unusual and probably underestimated cause of restenosis, which acquires special
      significance in this era of drug-eluting stents.

PMID- 16422134
TI  - Improving dietary self-monitoring and adherence with hand-held computers: a pilot
      study.
AB  - PURPOSE: Innovations in information technology offer new opportunities for
      creative application of personalized, tailored feedback strategies for improving
      dietary adherence. We developed and tested a real-time diet-monitoring and
      feedback system using hand-held computers. The goals were to increase diet self
      monitoring, reduce the burden of monitoring food intake, and increase adherence
      to dietary goals within a clinical trial. METHODS: Participants were 33 women in
      the Diet Modification arm of the Women's Health Initiative (WHI). After using
      focus groups to determine system features, women used the Personal Digital
      Assistant (PDA)-based system for 1 month and received immediate and weekly
      tailored feedback. The process and outcomes were evaluated using real-time food
      records collected through the PDAs; surveys; and self-reported food frequency
      questionnaires. RESULTS: Participants significantly increased self-monitoring,
      improved their attitudes toward self-monitoring, and met their dietary goals more
      often. Reported total fat intake and percent energy from fat decreased
      significantly. There was a modest decrease in mean caloric intake. DISCUSSION:
      The pilot study findings support the largely untapped potential of hand-held
      computers for improving diet monitoring and diet adherence, particularly within a
      clinical trial.

PMID- 16422135
TI  - Smoking among adolescents in China: an analysis based upon the meanings of
      smoking theory.
AB  - PURPOSE: This study utilized the Meanings of Behavior theory to examine whether
      meanings of smoking differ among adolescents in China who were never smokers,
      ever smokers, and past-30-day smokers. The Meanings of Behavior theory argues
      that affect takes precedence over cognitive constructs in motivating behavior
      This study also examined whether the associations among meanings of smoking and
      smoking behavior vary by age and gender DESIGN: This study was a cross-sectional
      study using survey data. SETTING: Middle and high schools in seven cities in
      China. SUBJECTS: A random sample of 4724 students comprised this study. MEASURE:
      A self-administered questionnaire asked about smoking behavior and incorporated
      the meanings of smoking scale. RESULTS: Overall prevalence rates of ever smokers
      and past-30-day smokers in this sample were 24.3% and 9.0%. Smoking was much more
      prevalent in boys than in girls. Students in the 11th grade were more likely than
      those in the 7th grade to have tried smoking at some time and to have smoked
      within the past 30 days. Odds ratios confirmed that meanings of smoking were
      significantly associated with smoking behaviors. CONCLUSIONS: Meanings of smoking
      are associated with smoking behavior among Chinese adolescents in that smoking
      may connote autonomy, control, or social relatedness. Prevention programs in
      China require new strategies to incorporate meanings of smoking in order to meet
      adolescent psychological needs for autonomy, competence, and social connections.

PMID- 16422136
TI  - Depressive symptoms and cigarette smoking in American workers.
AB  - PURPOSE: This study examined the relationship between depressive symptoms and
      cigarette smoking in a large sample of American workers. METHODS: We used data
      from the National Survey of Midlife Development in the United States. Seventy
      percent of individuals completed a telephone survey. The present study focused on
      2593 individuals working for pay. Measures included depressive symptoms, job
      level, and current smoking status. RESULTS: In a logistic regression analysis,
      depressive symptoms significantly predicted smoking status among workers (p <
      .01). In follow-up chi2 analyses, the link between depressive symptoms and
      smoking was consistent across gender (p < .01) and job levels (p < .01).
      DISCUSSION: Depressive symptoms among workers present an underlying obstacle to
      the success of worksite smoking cessation efforts. Findings highlight the need
      for increased cooperation between workplace mental health and medical health
      promotion programs and for tailoring smoking cessation programs to depressed
      workers. Limitations include self-report cross-sectional data and an
      underrepresentation of minority group members and individuals of low
      socioeconomic status.

PMID- 16422137
TI  - Hardiness and support at work as predictors of work stress and job satisfaction.
AB  - PURPOSE: To test a theoretically and empirically based model linking potential
      protective resources (hardiness, coworker and supervisor support) to the outcomes
      of work stress and job satisfaction and replicating the relationship of work
      stress to job satisfaction while accounting for the potential influence of
      negative affectivity. DESIGN: A cross-sectional research design using survey data
      collected from two convenience samples. SETTING: Two worksites: (1) a high-tech
      company and (2) a government agency. SUBJECTS: High-tech employees (N = 310;
      response rate, 73.8%) and government agency employees (N = 745; response rate,
      49.7%). MEASURES: The Dispositional Resilience Scale measured hardiness and the
      Positive and Negative Affect Schedule measured negative affectivity. Coworker and
      supervisor support were measured using the Coworker Support Scale and the
      Supervisor Support Scale, respectively. The Perceived Work Stress Scale measured
      work stress, and a single item from the Job Satisfaction Scale assessed overall
      job satisfaction. RESULTS: A multiple-group path analysis examined the proposed
      model. Similar patterns of association were found for both samples and suggested
      a more parsimonious model without the path from negative affectivity to job
      satisfaction. The model supports the protective nature of hardiness and support
      at work with regard to work stress and job satisfaction. CONCLUSION: Explanations
      of relationships depicted in the model, practical implications for reducing work
      stress and enhancing job satisfaction, limitations and future directions are
      discussed.

PMID- 16422138
TI  - Evaluating a yogic breathing and meditation intervention for individuals living
      with HIV/AIDS.
AB  - PURPOSE: To assess the effectiveness of a group program aimed at improving well
      being among individuals living with HIV/AIDS. METHODS: A randomized controlled
      trial was used to evaluate a residential program designed to teach breathing,
      movement, and meditation techniques. Sixty-two participants were recruited from
      community HIV/AIDS organizations. Fifteen withdrawals from the study left 47
      study participants. Standardized measures used were the Mental Health Index
      (MHI), the MOS-HIV Health Survey (MOS), and the Daily Stress Inventory (DSI),
      along with qualitative interviews. RESULTS: A repeated-measures analysis of
      variance indicated positive changes in well-being on the MHI and the MOS, where
      the effect was primarily seen immediately following the program and disappeared
      at later data points. The DSI indicated an increase in experience and impact of
      stress over time for the intervention group postprogram. Alternatively, the
      qualitative interviews described positive changes in how participants were living
      their day-to-day lives. CONCLUSION: In order to capture the outcomes of this
      program properly, both qualitative and quantitative measures are needed.

PMID- 16422139
TI  - The effect of mental distress on women's preventive health behaviors.
AB  - PURPOSE: To examine the relationship between mental distress and preventive
      health behaviors (i.e., mammograms, pap tests, physical exams) among women.
      METHODS: A cross-sectional design was employed. The sample consisted of 426 women
      from the Appalachian region in the United States who completed a comprehensive
      health survey. Mental distress was assessed by the 5-item Mental Health Index
      (MHI). Logistic regression was used to specify the models allowing for the
      control of covariates (i.e., marital status, education, recipient of Medicaid).
      RESULTS: Women who reported high mental distress were more likely to not get
      timely pap tests [OR = 1.64; 95% CI (1.10, 2.45); p < .05] or physical exams [OR
      = 1.68; 95% CI (1.07, 2.65); p < .05] than women who did not report being
      mentally distressed. A similar but less robust relationship was found between
      mental distress and timely mammograms. CONCLUSIONS: These findings suggest that
      mental distress affects the likelihood of engagement in preventive health
      behaviors.

PMID- 16422140
TI  - Evaluation of social-cognitive versus stage-matched, self-help physical activity
      interventions at the workplace.
AB  - PURPOSE: To compare the effectiveness of stage-matched vs. social-cognitive
      physical activity interventions in a work setting. Both interventions were
      designed as minimal-contact, self-help programs suitable for large-scale
      application. DESIGN: Randomized trial. Participants were randomized into one of
      the two intervention groups at baseline; the follow-up assessment was conducted 1
      month later. SETTING: A large, public university in the southeastern region of
      the United States. SUBJECTS: Employees from two academic colleges within the
      participating institution were eligible to participate: 366 employees completed
      the baseline assessment; 208 of these completed both assessments (baseline and
      follow-up) and met the compliance criteria. INTERVENTION: Printed, self-help
      exercise booklets (12 to 16 pages in length) either (1) matched to the
      individual's stage of motivational readiness for exercise adoption at baseline or
      (2) derived from social-cognitive theory but not matched by stage. MEASURES:
      Standard questionnaires were administered to assess stage of motivational
      readiness for physical activity; physical activity participation; and exercise
      related processes of change, decisional balance, self-efficacy, outcome
      expectancy, and goal satisfaction. RESULTS: The two interventions were equally
      effective in moving participants to higher levels of motivational readiness for
      regular physical activity. Among participants not already in maintenance at
      baseline, 34.9% in the stage-matched condition progressed, while 33.9% in the
      social-cognitive group did so (chi2 = not significant). Analyses of variance
      showed that the two treatment groups did not differ in terms of physical activity
      participation, cognitive and behavioral process use, decisional balance, or the
      other psychological constructs. For both treatment groups, cognitive process use
      remained high across all stages, while behavioral process use increased at the
      higher stages. The pros component of decisional balance did not vary across
      stage, whereas cons decreased significantly between preparation and action.
      CONCLUSIONS: Minimal-contact, one-shot physical activity interventions delivered
      at work can help people increase their participation in regular physical
      activity. Stage matching may not necessarily add value to interventions that
      otherwise make good use of behavior change theory. The findings also reinforce
      the importance of barrier reduction in long-term adherence. A limiting factor in
      this study is that employees in the earliest stage of change (precontemplation)
      were not well-represented in the sample.

PMID- 16422141
TI  - Suitability of commuting by bicycle to Arizona elementary schools.
AB  - PURPOSE: To determine the biking suitability (i.e., bikeability) of and
      prevalence of biking in 14 elementary schools representing two extremes of bused
      students (2.4% vs. 53.6%). METHODS: Street segments (within 0.25-mile radius of
      school) were scored for bikeability. Bikes in racks per school student population
      established biking prevalence. Mann-Whitney U-test compared bikeability and
      prevalence of biking between groups. RESULTS: A total of 12.5 +/- 2.2 streets per
      school were assessed. Thirteen schools scored very good (< 3.0) and one scored
      fair (4.0-4.9). Median bikeability score was 0.69 for the low-busing schools and
      0.53 for the high-busing schools (nonsignificant). Median biking prevalence was
      3.1% in the low-busing schools and 1.3% in the high-busing schools (p < .05).
      CONCLUSION: Streets surrounding schools were adequate for biking. Biking
      prevalence was significantly higher in low-busing schools but was relatively low
      in both low- and high-busing schools. Other factors, including intraindividual,
      social, school, and community, likely contribute to choice of biking to school.

PMID- 16422142
TI  - Employer coverage of clinical preventive services in the United States.
AB  - PURPOSE: To characterize employers' coverage of clinical preventive services.
      DESIGN: Mercer Human Resource Consulting Inc. included questions on clinical
      preventive services as part of its National Survey of Employer-Sponsored Health
      Plans, 2001. SETTING: A national sample of employers of a large, medium, and
      small number of employees, including governments. SUBJECTS: Respondents self
      identified as most knowledgeable about the organization's health benefits.
      MEASURES: Weighted analyses of responses to eight survey questions on health
      promotion. RESULTS: The survey was completed by 2180 employers, and the response
      rate was 21%. More than 90% of employers included increased productivity and
      decreased health care costs among their most important reasons for coverage of
      clinical preventive services. Within health insurance, coverage of physical
      examinations, immunizations, and screenings generally exceeded 50%, but coverage
      of lifestyle modification services was less than 20%. Only 20% of employers
      covered tobacco cessation services, and only 4% of employers provided an
      "optimal" benefit. We compared employers' offerings with a published ranking, by
      impact and value, of clinical preventive services. We found the biggest
      discrepancy in tobacco cessation services and alcohol problem prevention, which
      ranked high in terms of impact and value but are offered by only 20% and 18% of
      employers, respectively. CONCLUSIONS: Employers seek financial return from their
      offerings of clinical preventive services to employees, but they are least likely
      to offer the services most likely to provide this return.

PMID- 16422143
TI  - Status report on disease management efforts for the health promotion community.

PMID- 16422144
TI  - The effect of fostering on the genetic expression of locomotor sensitivity to
      alcohol.
AB  - Steps were taken to eradicate endemic mouse coronavirus from a colony that was
      part of a behavioral project characterizing the genetics of alcohol sensitivity.
      This behavioral study was conducted to determine whether changing the uterine or
      rearing environment (as is integral to common rederivation methods) would have a
      significant effect on the expression of the behavioral traits in question.
      Selected breeding pairs of the affected lines were divided into four treatment
      groups: 1) transfer of embryos to pseudopregnant B6D2F1 female mice, 2) fostering
      offspring to B6D2F1 dams, 3) fostering offspring to a different dam of the same
      line, and 4) offspring raised by the birth dam. Embryo transfers were successful
      only in one affected line. At approximately 50 days of age, the offspring were
      tested for locomotor behavior after intraperitoneal administration of ethanol or
      normal saline. There were no statistically significant effects of embryo transfer
      on the ethanol phenotype (ethanol-induced locomotor depression). Fostering
      significantly reduced the stimulant response to ethanol of only one mouse line
      selectively bred for high sensitivity to ethanol-induced stimulation, although
      the stimulant response of the fostered groups was still quite robust. Overall,
      the results of this study showed that eradication efforts involving fostering of
      offspring have a modest impact on the stimulant response to ethanol, but there
      were insufficient data to draw conclusions regarding the use of embryo transfer.

PMID- 16422145
TI  - The ex vivo pig eye as a replacement model for laser safety testing.
AB  - The purpose of this study was to evaluate the viability of ex vivo pig eyes as a
      replacement model for in vivo testing in the establishment of laser eye safety
      standards. Previous studies of pulsed energy absorption at 3.8 microm were
      performed using rhesus monkey cornea at pulse durations two orders of magnitude
      shorter than the 8-micros pulses used in the current study. Ex vivo pig eyes were
      exposed to laser pulses of various energies and then evaluated to establish the
      statistical threshold for corneal damage. Tissue analysis (histologic evaluation)
      was used to determine the extent of damage to the cornea. These results can be
      used in the establishment of safety standards for laser use; our findings also
      suggest that ex vivo pig eyes are suitable models for this purpose.

PMID- 16422146
TI  - Murine xenograft model of Spirocerca lupi-associated sarcoma.
AB  - Nodular masses and granulomas of the esophagus are among the most frequent
      lesions caused by Spirocerca lupi, a nematode parasite of dogs, and neoplastic
      transformation of these granulomas to osteosarcoma or fibrosarcoma has been
      described. In this study, we developed a xenograft murine model of S. lupi
      associated sarcoma. Samples of esophageal fibrosarcoma and osteosarcomas were
      excised from three dogs diagnosed with spirocercosis. These sarcomas were
      inoculated into three groups of 6-week-old NOD/SCID mice to create three tumor
      lines of S. lupi-associated sarcomas. Mice in all groups developed tumors after
      inoculation, and the cell lines could be further propagated as second-generation
      xenografts. We successfully established xenograft murine models of three
      different lines of S. lupi-associated sarcoma that offer readily available
      sources of these tumors for further experiments. This resource will facilitate
      studies on the malignant transformation of the granulomas, establishment of
      efficient chemotherapy and radiotherapy regimens, and identification of
      diagnostic molecular markers.

PMID- 16422147
TI  - Evaluation of Helicobacter hepaticus bacterial shedding in fostered and sex
      segregated C57BL/6 mice.
AB  - Neonatal fostering has been evaluated as a means of eliminating Helicobacter
      hepaticus infection in laboratory mouse colonies. The purpose of the present
      study was to evaluate cross-fostering of neonatal C57BL/6 pups from
      experimentally infected dams after male-absent parturition and to determine the
      effects of sex and housing strategy on H. hepaticus populations. Approximately 20
      C57BL/6 mice (age, 1 to 4 days) were fostered daily. In all fostered mice, fecal
      samples collected at 21 and 42 days of age and cecal samples collected at 42 days
      of age tested negative for H. hepaticus by polymerase chain reaction analysis.
      Our results demonstrate that removal of the male prior to parturition extends the
      fostering period to yield Helicobacter-free mice. In a second experiment, the
      effects of time of infection, housing strategy, and sex on fecal H. hepaticus
      shedding and cecal colonization were evaluated. Neither time nor housing strategy
      affected bacterial shedding. In contrast, fecal and cecal bacterial loads were
      higher in male mice versus female mice. A novel predictive algorithm was
      developed to predict cecal bacterial colonization levels in light of fecal
      bacterial loads. Our findings likely will prove useful in Helicobacter
      eradication efforts and in studies designed to further elucidate the role of H.
      hepaticus in disease.

PMID- 16422149
TI  - Adaptation of Plasmodium vivax to growth in owl monkeys (Aotus nancymai).
AB  - The purpose of this study was reactivation and adaptation of a strain of
      Plasmodium vivax to Aotus nancymai monkeys. A need arose for malarial parasites
      for use in serologic and molecular studies and for teaching slides. This
      particular strain of parasite had been characterized previously as producing high
      density parasitemia in splenectomized New World monkeys and therefore represented
      a good candidate for reactivation. P. vivax (Vietnam II), isolated in 1970, was
      reactivated after adaptation in Aotus lemurinus griseimembra monkeys nearly 33
      years earlier and adapted to A. nancymai monkeys. Passage was achieved by
      intravenous inoculation of parasite blood stages into splenectomized A. nancymai
      monkeys. Parasitemia was determined by analyzing daily blood smears stained with
      Giemsa. Maximum parasite counts ranged from 10,630 to 94,000 parasites/microl;
      the mean maximum parasite count for the four animals was 39,565 parasites/microl.
      Parasite counts of > 10,000/microl were maintained for 2 to 64 days. After only
      three passages of the parasite, attempts to reactive were successful. A. nancymai
      proved a suitable animal model for the recovery of this parasite. In conclusion,
      successful reactivation and adaptation of this parasite offers the capability to
      perform a series of diagnostic, immunologic, and molecular studies as well as to
      provide otherwise potentially unavailable teaching materials to healthcare
      professionals.

PMID- 16422148
TI  - Characterization of cyclicity and hormonal profile with impending ovarian failure
      in a novel chemical-induced mouse model of perimenopause.
AB  - 4-Vinylcyclohexene diepoxide (VCD) causes early, gradual ovarian failure in mice
      because it specifically targets small pre-antral ovarian follicles. The period
      between loss of these follicles and ovarian failure is analogous to perimenopause
      in women. We sought to characterize the period of onset of ovarian failure in VCD
      treated mice in regard to estrous cycle length and hormonal changes. Female
      C57Bl/6 mice (age, 28 days) were dosed daily for 15 days with VCD (160 mg/kg
      intraperitoneally) to cause early ovarian failure or with vehicle only (control
      animals). Cycle length was monitored by vaginal cytology. Plasma levels of 17beta
      estradiol (E2), progesterone (P4), and follicle-stimulating hormone (FSH) in
      control and VCD-treated animals were measured during proestrus of cycles 1
      through 12. Cycle length (mean, 5.8 days) did not differ between groups for
      cycles 1 through 4. In contrast, cycle length during cycles 5 through 12 was
      increased (mean length, 10.9 days; P < 0.05 versus control) in VCD-treated
      animals, which also showed an apparent increase in plasma FSH levels. Plasma E2
      and P4 at proestrus did not differ between groups during any cycle. Ovarian
      failure in VCD-treated mice was confirmed by histological evaluation on day 156
      after onset of dosing, whereas control animals were still cycling. Therefore,
      despite compromised cycle length in VCD-treated mice, peak ovarian steroid
      production in preovulatory follicles at proestrus is adequate. These results
      demonstrate that the VCD-treated mouse can serve as an appropriate model to mimic
      hormonal changes during the perimenopausal transition in women.

PMID- 16422150
TI  - Zinc-induced survival of Leydig cells in Fischer rats (Rattus norvegicus) treated
      with cadmium chloride.
AB  - Zinc is known to prevent cadmium-induced carcinogenesis and Leydig cell
      destruction in rat testes; however, the mechanism of action is not known,
      although it has been suggested that pituitary feedback increases the production
      of luteinizing hormone (LH) in response to low circulating androgen. We therefore
      examined the biological role of zinc in reducing cadmium toxicity in the Leydig
      cells of Fischer rats. Two groups of eleven 6-month-old rats were injected
      subcutaneously with 20 micromol CdCl2/kg weekly for 5 weeks; one of these groups
      also received 1 mmol/kg zinc acetate weekly for the same 5 weeks. A third group
      of rats received 1 mmol/kg zinc acetate weekly, and a fourth group was injected
      with saline weekly for 5 weeks. After 8 months of study, the animals were
      euthanized by CO2 inhalation. The results indicated that the number of surviving
      Leydig cells was significantly lower in the cadmium group (7.34% = 0.095 x
      10(9)/cm3) than in the cadmium-zinc group (20.85%) or control animals (91.2%).
      Moreover, the concentrations of serum testosterone and LH were significantly
      higher in the cadmium group than in any of the other groups. This difference
      probably was due to the testosterone produced by a small reservoir of surviving
      Leydig cells and to other endocrine factors. These findings suggest that Fischer
      rat testis may be a good model system for testing the effects of cadmium and zinc
      on the production of LH and testosterone and other androgens before spontaneous
      cancers develop.

PMID- 16422151
TI  - Transforming care at the bedside: using a team approach to give nurses--and their
      patients--new voices in providing high-quality care.
AB  - To transform care at the bedside, 13 hospitals across the country have taken new
      approaches to involving staff members and patients-thinking outside the box about
      what care should be as opposed to what it actually is. The result has been a new
      way of communicating and a new way of delivering high-quality care.

PMID- 16422152
TI  - In search of a high-performing health system.
AB  - Healthcare today in the United States could be described as "the best of times
      and the worst of times," according to James Mongan, MD, president and CEO of
      Partners HealthCare System in Boston. On one hand, the U.S. appears to have the
      best healthcare in the world, but on the other hand, it has an underperforming
      system whose costs are disproportionately higher than those of other
      industrialized nations.

PMID- 16422153
TI  - Addressing the barriers to greater implementation of electronic health records.
AB  - A recent study released last month by RAND researchers said that widespread
      adoption of electronic health record systems and networking could eventually save
      more than dollar 81 billion annually through improvement of healthcare efficiency
      and safety.

PMID- 16422154
TI  - Light coupling into an optical microcantilever by an embedded diffraction
      grating.
AB  - By measuring the excitation efficiency of an optical waveguide on a diffraction
      grating one can accurately register the changes in the incidence angle of the
      exciting light beam. This phenomenon was applied to detect ultrasmall deflections
      of silicon dioxide cantilevers of submicrometer thickness that were fabricated
      with corrugation on top to act as diffraction grating couplers. The power of
      light coupled into the cantilevers was monitored with a conventional
      photodetector and modulated using mechanical vibration of the cantilever, thus
      changing the spatial orientation of the coupler with respect to the incident
      light beam. The technique can be considered as an alternative to the methods
      known for detection of cantilever deflection.

PMID- 16422155
TI  - Unified analysis and mathematical representation of film-thickness behavior of
      film-substrate systems.
AB  - The ellipsometric function p of a film-substrate system is studied as the film
      thickness d is kept constant and the angle of incidence phi is changed. The
      generated constant-thickness contours (CTCs) are characterized by an introduced
      mathematical behavior indicator that represents a group of CTCs. The behavior of
      each group is developed and studied in the four planes phi-d, X, Z, and p, where
      X is the film-thickness exponential function and Z is a previously introduced
      intermediate plane. In the phi-d plane the film-thickness domain is identified
      and divided into a sequence of disconnected thickness subdomains (DTSs),
      depending on only N0 and N1, and their number depending on the range in which
      N0/N1 lies. The behavior of the CTCs in the successive planes X, Z, and p is then
      studied in each DTS, and the CTC's space is divided into disconnected subfamilies
      according to the behavior indicator. Equivalence classes that reduce the infinite
      number of subfamilies into a finite number are then introduced. The
      transformation from each plane to the next is studied with the origin of the Z
      plane mapped onto the point at infinity of the p plane, forming a singularity. A
      multiple-film-thickness inequality is derived to determine the unique solution of
      the film thickness. The type of reflection being internal or external at both
      ambient-film and film-substrate interfaces affects the analysis and is also
      considered. To conclude we introduce the design of polarization-preserving
      devices and a novel oscillating single-element ellipsometer to fully characterize
      zero film-substrate systems as examples of applying the knowledge developed here.

PMID- 16422156
TI  - Attenuation of laser-generated shock waves in Plexiglas.
AB  - A simple analytic model is derived for describing the attenuation of a shock wave
      in a Plexiglas plate. At the same time, experimental measurements are presented
      with a well-designed optical-fiber sensor based on detection-beam deflection. The
      amplitude of the shock-wave pressure is measured experimentally and calculated
      numerically for analytic expressions at different distances from the region of
      the surface breakdown by the radiation of a single-pulse Nd:YAG laser. Good
      agreement between the experimental and the calculated values of the shock-wave
      pressure is established.

PMID- 16422157
TI  - Two-wave-plate compensator method for full-field retardation measurements.
AB  - The two-wave-plate compensator (TWC) method is expanded for full-field
      retardation measurements by use of a polarization microscope. The sample image is
      projected onto a CCD camera connected to a computer, allowing the retardation to
      be measured at all pixels. The retardation accuracy of this implementation of the
      TWC is evaluated to be 0.06 nm. The method is applied to polarization-maintaining
      fibers and long-period fiber gratings. The measured retardation is in good
      agreement with the crossed-polarizer images of the fibers. The method achieves a
      spatial resolution of 0.45 microm and a retardation resolution of 0.07 nm. The
      full-field TWC method can thus be a useful tool for characterizing and monitoring
      the fabrication of optical devices.

PMID- 16422158
TI  - Aberration measurement of projection optics in lithographic tools by use of an
      alternating phase-shifting mask.
AB  - As a critical dimension shrinks, the degradation in image quality caused by
      wavefront aberrations of projection optics in lithographic tools becomes a
      serious problem. It is necessary to establish a technique for a fast and accurate
      in situ aberration measurement. We introduce what we believe to be a novel
      technique for characterizing the aberrations of projection optics by using an
      alternating phase-shifting mask. The even aberrations, such as spherical
      aberration and astigmatism, and the odd aberrations, such as coma, are extracted
      from focus shifts and image displacements of the phase-shifted pattern,
      respectively. The focus shifts and the image displacements are measured by a
      transmission image sensor. The simulation results show that, compared with the
      accuracy of the previous straightforward measurement technique, the accuracy of
      the coma measurement increases by more than 30% and the accuracy of the spherical
      aberration measurement increases by approximately 20%.

PMID- 16422159
TI  - Optimization of compact lateral, vertical, and combined tapered spot-size
      converters by use of the beam-propagation method.
AB  - A study of lateral, vertical, and combined spot-size converters is presented that
      employs full-vectorial numerical techniques such as modal solution and beam
      propagation based on the finite-element method. Spot-size expansion, coupling
      efficiency to an optical fiber, the mode-beating phenomenon, and transmission
      losses are demonstrated for all three spot-size-converter designs. Optimization
      of the device fabrication parameters is also reported. A significant improvement
      in the coupling efficiency and reduction of the device length are achieved when
      the length and the width are changed simultaneously.

PMID- 16422160
TI  - Microarrays of silver nanowires embedded in anodic alumina membrane templates:
      size dependence of polarization characteristics.
AB  - Polarization characteristics of microarrays of silver nanowires embedded in an
      anodic alumina membrane are theoretically investigated. The microarrays mainly
      transmit the p-polarized wave, whereas they strongly attenuate the s-polarized
      wave in the near- and mid-infrared spectral range. We show that the sizes (e.g.,
      diameter, spacing, and ratio of diameter to spacing) of the nanowires strongly
      affect the optical losses for the polarized waves. It is predicted that large
      extinction ratios and small insertion losses can be simultaneously achieved by an
      appropriate choice of the ratio and the diameter. An optimized design of a
      nanowire grid polarizer at near- and mid-infrared wavelengths is presented.

PMID- 16422161
TI  - Replication of a holographic ion-etched spherical blazed grating for use at
      extreme-ultraviolet wavelengths: topography.
AB  - We have measured the topography of a holographic ion-etched spherical blazed
      grating and three of its replicas using an atomic force microscope. The master
      grating had a roughness of less than 5 angstroms rms, a blaze angle of 2.5
      degrees, and an antiblaze angle of 3.3 degrees. Thus the groove profile was more
      triangular than sawtooth. We find that the replication process did not
      significantly change the master grating. Moreover, we find no significant
      difference in roughness, blaze angle, or antiblaze angle between the master and
      its replicas before or after multilayer coating. However, bumps were observed on
      the gratings after coating, the cause of which is not understood. Although
      widespread, they occupy a relatively small fraction of the total area.

PMID- 16422162
TI  - Replication of a holographic ion-etched spherical blazed grating for use at
      extreme-ultraviolet wavelengths: efficiency.
AB  - Using synchrotron radiation, we have measured the efficiency at an angle of
      incidence of 10 degrees of a holographic ion-etched spherical blazed grating and
      three of its fourth-generation replicas. The measured efficiency profile of
      replicas 1 and 3 prior to multilayer coating oscillated from thin-film
      interference produced by the replicas' Al/Al2O3/SiO2 structure. A Mo2C/Si
      multilayer coating was applied to the master grating and replicas 1 and 2. After
      coating, the maximum grating efficiency occurred in the -2nd order and the
      maximum values were 12.4% at 143.8 angstroms for the master and 11.6% at 145.2
      angstroms for replicas 1 and 2. On the basis of measurements obtained after
      coating, the derived groove efficiency was 22.2% for the master, 19.4% for
      replica 1, and 19.3% for replica 2. The groove efficiency of the uncoated replica
      3 was 24.3% at 142.5 angstroms. We find that the replicas are reasonably faithful
      copies of the ion-etched master, and models based on measured atomic force
      microscope groove profiles are in general agreement with measured results.
      However, subtle issues remain regarding the widths of the peak order profile and
      the location of its maximum wavelength.

PMID- 16422163
TI  - Assessment of blood supply in superficial tissue by polarization-gated elastic
      light-scattering spectroscopy.
AB  - We report the feasibility of monitoring both hemoglobin oxygen saturation and
      hemoglobin concentration in the superficial layer of tissue using polarization
      gated elastic light-scattering spectroscopy. We detail our analysis technique,
      the experimental validation of our analysis, and the detection of an early
      increase in blood supply to the superficial layer of colon tissue in human
      patients with colonic adenomas as well as in an animal model of colon
      carcinogenesis. To the best of our knowledge, this study represents the first
      evidence that polarization gating can be used as a spectroscopic tool to quantify
      hemoglobin concentration as well as oxygen saturation in the uppermost tissue
      layer.

PMID- 16422164
TI  - Multigigahertz range-Doppler correlative signal processing in optical memory
      crystals.
AB  - Analog optical signal processing of complex radio-frequency signals for range
      Doppler radar information is theoretically described and experimentally
      demonstrated using crystalline optical memory materials and off-the-shelf
      photonic components. A model of the range-Doppler processing capability of the
      memory material for the case of single-target detection is presented. Radarlike
      signals were emulated and processed by the memory material; they consisted of
      broadband (> 1 GHz), spread-spectrum, pseudorandom noise sequences of 512 bits in
      length, which were binary phase-shift keyed on a 1.9 GHz carrier and repeated at
      100 kHz over 7.5 ms. Delay (range) resolution of 8 ns and Doppler resolution of
      130 Hz over 100 kHz were demonstrated.

PMID- 16422165
TI  - Second-order robust regularization cost function for detecting and reconstructing
      phase discontinuities.
AB  - We propose a robust method for computing discontinuous phase maps from a fringe
      pattern with carrier frequency. Our algorithm is based on the minimization of an
      edge-preserving regularized cost function, specifically, on a robust regularized
      potential that uses a paradigm called the plate with adaptive rest condition,
      i.e., a second-order edge-preserving potential. Given that the proposed cost
      function is not convex, our method uses as its initial point an overly smoothed
      phase computed with a standard fringe analysis method and then reconstructs the
      phase discontinuities. Although the method is general purpose, it is introduced
      in the context of interferometric gauge-block calibration. The performance of the
      algorithm is demonstrated by numerical experiments with both synthetic and real
      data.

PMID- 16422166
TI  - Achieving stabilization in interferometric logic operations.
AB  - Interferometric systems with amplitude beam splitters can implement reversible
      operations that, on detection, become Boolean operators. Being passive, they
      consume no energy, do not limit the operating bandwidth, and have negligible
      latency. Unfortunately, conventional interferometric systems are notoriously
      sensitive to uncontrolled disturbances. Here the use of polarization in a common
      path interferometric logic gate with and without polarization beam splitters is
      explored as an attractive alternative to overcome those difficulties. Two of
      three device configurations considered offer significant stability and lower
      drive modulator voltage as advantages over the previous systems. The first
      experimental tests of such a system are reported. Common-path interferometry
      lends itself to even more stability and robustness by compatibility with no-air
      gap, solid optics.

PMID- 16422167
TI  - Comment on "partially coherent flat-topped beam and its propagation".
AB  - We point out that the expression of the cross-spectral density (CSD) of a
      partially coherent flat-topped beam (PCFB) given by Ge et al. [Appl. Opt. 43,
      4732 (2004)] is incorrect. The results show that the M2 factor derived based on
      Ge's expression leads to M2 < 1 in some cases, which is physically unacceptable.
      A new expression of the CSD for a PCFB is given.

PMID- 16422168
TI  - Temperature stability of a dichroic atomic vapor laser lock.
AB  - We have investigated the temperature stability of the dichroic atomic vapor laser
      lock laser frequency lock method. We find that, in general, the lock exhibits
      significant temperature sensitivity, leading to laser frequency drifts as large
      as tens of MHz/K. However, for certain configurations of the optical elements of
      the system, this temperature dependence is reduced to below 1 MHz/K. These
      temperature-independent points can be found across a broad range of frequencies.
      We present a numerical model that reproduces the general behavior of the system.

PMID- 16422169
TI  - Optical parametric chirped-pulse amplifier and spatiotemporal shaping for a
      petawatt laser.
AB  - We present a degenerate noncollinear optical parametric chirped-pulse amplifier
      pumped by a high-energy, diode-pumped Nd:Glass regenerative amplifier delivering
      monomode pulses at 527 nm. The spatial mode shaping of the pump pulses is
      achieved with a diffractive laser cavity element, and temporal pulse shaping
      makes use of an electro-optic modulator and an arbitrary electrical waveform
      generator. Amplification at gain saturation achieves tailoring of the signal
      pulses. Numerical simulations with Miro software are presented and compared with
      experimental measurements.

PMID- 16422170
TI  - High-speed Shack-Hartmann wavefront sensor design with commercial off-the-shelf
      optics.
AB  - Several trade-offs relevant to the design of a two-dimensional high-speed Shack
      Hartmann wavefront sensor are presented. Also outlined are some simple
      preliminary experiments that can be used to establish critical design
      specifications not already known. These specifications include angular
      uncertainty, maximum measurable wavefront tilt, and spatial resolution. A generic
      design procedure is then introduced to enable the adaptation of a limited
      selection of CCD cameras and lenslet arrays to the desired design specifications
      by use of commercial off-the-shelf optics. Although initially developed to aid in
      the design of high-speed (i.e., megahertz-frame-rate) Shack-Hartmann wavefront
      sensors, our method also works when used for slower CCD cameras. A design example
      of our procedure is provided.

PMID- 16422171
TI  - Prognostic factors after potentially curative resection in stage II or III colon
      cancer.
AB  - It is important to identify factors that are predictive of outcome after a
      curative resection in colon cancer in order to optimize adjuvant therapy. To
      investigate these prognostic factors we conducted a retrospective analysis of our
      clinicopathological data. A total of 190 patients with a pathological stage II or
      III colon cancer underwent potentially curative resection with lymphadenectomy at
      our hospital between 1990 and 1998. These patients received no preoperative
      chemotherapy, immunotherapy or radiotherapy. Postoperative adjuvant chemotherapy
      using oral fluoropyrimidines was performed in 127 patients, and the other 63
      patients underwent surgery alone. Univariate and multivariate analyses for
      prognostic factors were carried out. The univariate analysis revealed that
      invasion to adjacent organs, N1-2, positive mesenteric lymph node metastasis
      (MLN+), lymphatic permeation (ly)1-3, venous invasion (v)1-3, and v2-3 were each
      significant factors indicating worse disease-free survival, and that N1-2, MLN+,
      ly1-3, v1-3 and v2-3 were each significant factors for worse overall survival. In
      the multivariate analysis, MLN+ and vl-3 were significant factors for worse
      disease-free survival, and for worse overall survival. In conclusion, stage II or
      III colon cancer patients positive for mesenteric lymph node metastasis or for
      venous invasion have a greater risk of recurrence and death after potentially
      curative resection. Postoperative adjuvant chemotherapy using oral
      fluoropyrimidines did not significantly reduce the risk of recurrence and death
      in these patients. More effective adjuvant chemotherapy than oral
      fluoropyrimidine should be considered, especially in such high-risk patients.

PMID- 16422172
TI  - Surgery and clinicopathological features of gastric adenocarcinoma involving the
      esophago-gastric junction.
AB  - To clarify the optimal operative procedure for gastric adenocarcinoma involving
      the esophago-gastric junction (EGJ), we investigated 49 cases with an upper
      gastric cancer invading the esophagus who underwent surgical treatment in our
      department during the period from 1991 to 2000. According to Siewert's
      classification, there were 21 cases with a type II tumor, and 28 cases with a
      type III tumor. Twenty-five cases underwent surgery through an abdominal approach
      only. The remaining 24 cases were operated on via a left thoraco-abdominal
      approach. Eight (33%) of 24 cases who underwent extended lymphadenectomy through
      a left thoraco-abdominal approach had lower mediastinal lymph node metastasis.
      Metastasis was observed in cases with cancer invasion more than 2 cm from the
      EGJ. There were 6 cases with a T1 tumor, 6 with a T2 tumor, 27 with a T3 tumor,
      and 10 with a T4 tumor. Incidences of lymph node metastasis were 0% for T1, 67%
      for T2, 81% for T3, and 80% for T4. Proximal gastrectomy was performed in 6 cases
      at the early stage and in 10 cases at the advanced stage with distant metastasis
      (M1). Total gastrectomy was done in 33 cases at the advanced stage, and 3 of
      these 33 cases had metastasis to the parapyloric lymph nodes. We performed
      combined resection of the body and tail of the pancreas and the spleen in 7
      cases. One of these 7 cases had direct invasion to the pancreas and 6 cases had
      remarkable metastasis to the lymph nodes along the splenic artery. Splenectomy
      preserving the pancreas was done in 24 cases. The incidences of metastasis of the
      lymph nodes along the splenic artery and the splenic hilum were 25% and 17%,
      respectively. We performed partial resection of the diaphragm surrounding the
      esophageal hiatus in 15 cases through a left thoraco-abdominal approach. Six
      cases had metastasis to the diaphragm and nine cases had direct invasion to the
      diaphragm. Tumors were stage I in 8 cases, II in 5 cases, III in 13 cases and IV
      in 23 cases, and the curability was categorized as A in 8 cases, B in 20 and C in
      21. The overall 5-year-survival rate was 25%, and the rates according to cancer
      stage were 86% for stage I, 40% for stage II , 21% for stage III and 0% for stage
      IV. The 5-year survival rates of cases at stage II and III were 33% for cases
      using the left thoraco-abdominal approach and 28% for cases with the abdominal
      approach. Based on these results, we recommend distal esophagectomy with total
      gastrectomy, and occasional combined resection of the spleen and the diaphragm
      through a left thoraco-abdominal approach for advanced gastric adenocarcinoma
      involving the EGJ.

PMID- 16422173
TI  - Pigment epithelium-derived factor as a new diagnostic marker for melanocytic
      tumors.
AB  - Pigment epithelium-derived factor (PEDF), a potent antiangiogenetic factor, has
      been lately known to correlate well with angiogenic and metastatic potentials of
      tumor cells. We investigated the expression of PEDF protein in various types of
      human tumor cells by an immunohistochemical technique using a monoclonal
      antibody. Consequently, we found the significantly frequent and intense
      expression of PEDF in human melanocytic tumor cells including malignant melanoma
      as compared to non-melanocytic ones. We evaluated the diagnostic usefulness of
      anti-PEDF antibody in melanocytic tumors by comparing its immunoreactive
      sensitivity with that of other conventional melanocytic markers such as S-100
      protein, HMB-45 and Melan-A, and found that PEDF possess the equal ability to
      others on its sensitivity. We finally concluded that PEDF is a useful diagnostic
      marker for melanocytic tumors, especially malignant melanomas, by its use in
      combination with other markers.

PMID- 16422174
TI  - Vascular endothelial growth factor is involved in angioedema associated with
      eosinophilia.
AB  - Angioedema associated with eosinophilia is a disorder characterized by angioedema
      and eosinophilia. However, the pathogenesis of this disorder has not been fully
      understood. We experienced 4 patients with angioedema associated with
      eosinophilia. All patients were young, 3 were female and 1 was male. All patients
      revealed edema of the limbs and eosinophilia. The symptom was rapidly improved
      after the initiation of low or medium dose of prednisolone. We evaluated the
      serum concentration of interleukin 5 (IL-5) and the plasma concentration of
      vascular endothelial growth factor (VEGF) in 1 patient. Both cytokines were
      markedly elevated before the treatment and decreased after the treatment.
      Angioedema associated with eosinophilia is not so rare, and IL-5 and VEGF are
      involved in the pathogenesis of this disease.

PMID- 16422175
TI  - Scleroderma and repeated spontaneous abortions treated with vitamin E--a case
      report--.
AB  - A 33-year-old woman was referred to our hospital due to repeated spontaneous
      abortions and positive autoantibodies. She had noticed Raynaud's phenomenon 13
      years earlier. We diagnosed scleroderma based on the presence of Raynaud's
      phenomenon, proximal scleroderma, presence of anti-centromere antibodies, and
      histological findings on skin biopsy. Neither lupus anticoagulant nor anti
      cardiolipin-beta2-glycoprotein 1 antibody was detected. We administered
      tocopherol nicotinate. Five months after the initiation of the treatment, she
      became pregnant and later delivered a healthy baby.

PMID- 16422176
TI  - Partial spontaneous regression of hepatocellular carcinoma: a case with high
      concentrations of serum lens culinaris agglutinin-reactive alpha fetoprotein.
AB  - Spontaneous regression of hepatocellular carcinoma (HCC) is rare. There are few
      reports discussing spontaneous regression associated with serum lens culinaris
      agglutinin-reactive alpha fetoprotein (AFP-L3). We describe a case of HCC with a
      high level of AFP-L3, which showed a rapid increase in alpha fetoprotein (AFP)
      concentration after partial spontaneous regression, and which was then treated
      successfully. A 71-year-old woman suffering from chronic hepatitis C underwent
      surgical resection for HCC. Preoperative concentrations of AFP fluctuated;
      subsequent to a transient decrease, a rapid increase in AFP was observed. AFP-L3
      concentration was extremely high. The resected tissue consisted of encapsulated
      moderately differentiated HCC, subcapsular coagulation necrosis, and chronic
      active hepatitis. The postoperative course was uneventful. At present, 24 months
      after diagnosis, no symptoms or signs of tumor recurrence or metastasis have been
      observed. Although the precise etiology of the spontaneous regression in this
      patient is not known, we speculate that spontaneous regression of tumor cells
      with high malignant potential may be related to arterial involvement and
      insufficient blood supply.

PMID- 16422177
TI  - Carcinoid tumor of the Vater's papilla presenting with chronic pancreatitis--a
      case report--.
AB  - Carcinoid tumors are common in the duodenum except for in the Vater's papilla [1
      9]. We report here a case of carcinoid tumor arising in the Vater's papilla with
      repeated episods of pancreatitis. The patient is a 28 year-old-woman who had
      repeated abdominal pain with elevated serum amylase and had been treated as
      chronic pancreatitis. Computed tomography (CT) revealed a slight dilatation of
      the main pancreatic duct from the pancreatic head to the tail, and mild swelling
      of the pancreas. A submucosal tumor measuring 1.3 cm in diameter was detected in
      the ampulla of Vater by esophagogastroduodenscopy (EGD), and total papillectomy
      was performed under the suspicious of carcinoid tumor. The tumor was not
      encapsulated, 1.0 cm in diameter, undefined, and whitish in color. Histologically
      monomorphic tumor cells with lightly eosinophlic cytoplasm and round nuclei
      proliferate in trabecular and solid patterns. Immunohistochemically tumor cells
      were positive for neuron-specific enolase, chromogranin A and synaptophysin, and
      the tumor was diagnosed as carcinoid tumor. It should be noted that carcinoid
      tumor in the ampulla may occur with initial signs of acute or chronic
      pancreatitis.

PMID- 16422178
TI  - Pioneering figures in medicine: Albert Bruce Sabin--inventor of the oral polio
      vaccine.
AB  - Over ten years after his death, the Sabin oral vaccine continues its profound
      influence on public health throughout the world. The annual incidence of polio
      has fallen dramatically since its introduction, with more than 300,000 lives
      being spared each year and an annual global saving in excess of 1 billion US
      dollars. In many ways, the development of an effective oral vaccine and its
      subsequent regulation by the World Health Organization can serve as a model for
      medical researchers. Our review describes the contribution of Albert Sabin as a
      medical researcher, and how his vaccine had a profound impact on the global
      reduction of polio infections. As many different factors influenced health-care
      last century, we describe Sabin's involvement with respect to prevailing
      scientific paradigms and public health issues of the time. Our paper also
      outlines the basic epidemiology of poliovirus and the historical development of
      an effective vaccine, both with and without Albert Sabin.

PMID- 16422179
TI  - Community-acquired pneumonia in children: from diagnosis to treatment.
AB  - Community-acquired pneumonia (CAP) in children is a leading cause of childhood
      morbidity and mortality mainly in the developing world. Its etiology can be
      viral, bacterial, or mixed infection. The etiological agents are different in
      different age groups and during the various seasons of the year. Chest X-rays and
      inflammatory laboratory tests have low diagnostic sensitivity and specificity.
      CAP in children has an important impact on society and is a frequent cause of
      physician visits, work loss, and reduction of quality of life of the children and
      his/her family. The use of treatment algorithms in the developing countries has
      led to lower mortality rates, but the future of this approach, given the rate of
      development of antimicrobial resistance, is uncertain. The wider use of
      pneumococcal vaccines may represent an important advance in the prevention of
      pneumonia caused by Streptococcus pneumoniae.

PMID- 16422180
TI  - Avian influenza.
AB  - Influenza is an old disease but remains vital nowadays. Three types of influenza
      viruses, namely A, B, C, have been identified; among them influenza A virus has
      pandemic potential. The first outbreak of human illness due to avian influenza
      virus (H5N1) occurred in 1997 in Hong Kong with a mortality of 30%. The most
      recent outbreak of the avian influenza epidemic has been going on in Asian
      countries since 2003. As of March 2005, 44 incidental human infections and 32
      deaths have been documented. Human influenza viruses differ with other avian
      influenza viruses on the choice of cellular receptors. Avian influenza viruses
      bind to cell-surface glycoproteins or glycolipids containing terminal sialyl
      galactosyl residues linked by 2-3-linkage [Neu5Ac(alpha2-3)Gal], whereas human
      viruses, including the earliest available isolates from the 1957 and 1968
      pandemics, bind to receptors that contain terminal 2-6-linked sialyl-galactosyl
      moieties [Neu5Ac(alpha2-6)Gal]. Recent evidence suggests that human bronchial
      ciliated epithelial cells contain Neu5Ac(alpha2-3)Gal and can be infected with
      avian influenza viruses. Nevertheless, avian influenza viruses can not infect non
      ciliated bronchial epithelial cells. Hence, adaptation of the avian influenza
      virus to nonciliated cells is a prerequisite for a pandemic virus to emerge.
      Biological behaviors of influenza viruses indicate that once a pandemic virus
      emerges, isolation is not likely to contain this epidemic. A specific vaccine
      against the pandemic strain will not be available until 6 to 12 months after the
      inception of the pandemic. Judicious use of antiviral agents and stringent
      disease control measures are imperative to decrease the impact of a future
      pandemic.

PMID- 16422181
TI  - Use of antimicrobial agents for upper respiratory tract infections in Taiwanese
      children.
AB  - Upper respiratory tract infections (URTIs) are mostly caused by viruses.
      Antibiotic misuse for viral URTIs in children is a serious problem that not only
      results in selection of resistant strains of bacteria but also wastes millions of
      dollars each year in Taiwan. Antibiotic resistance among common respiratory
      bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae,
      Staphylococcus aureus, and Moraxella catarrhalis has become a major issue for
      public health. The common cold, acute pharyngotonsillitis, acute otitis media,
      acute sinusitis, acute bronchitis, influenza and acute epiglottitis are the most
      frequently encountered acute URTIs in out-patient clinics. This article
      recommends the judicious use of antimicrobial agents for these seven common
      pediatric URTIs, based on local epidemiological data and the recommendations of
      the Infectious Disease Society of Taiwan and the American Academy of Pediatrics.
      With education and behavior modification, practitioners will help to reduce
      antibiotic overuse, and the goal of reducing antimicrobial resistance may be
      accomplished.

PMID- 16422182
TI  - Pneumococcal vaccines.
AB  - Streptococcus pneumoniae is the leading bacterial pathogen of infectious diseases
      in children and adolescents. The 23-valent pneumococcal polysaccharide vaccine
      could prevent invasive pneumococcal infection with broader serotype coverage but
      still has some limitations. On the other hand, 7-valent pneumococcal conjugate
      vaccine has been shown to decrease cases of nasopharyngeal acquired S. pneumoniae
      vaccine serotypes and proved herd immunity. The safety and efficacy against
      vaccine serotype pneumococcal diseases have been documented. However, the
      potential risk of increasing non-vaccine serotype pneumococcal diseases should be
      considered. This article reviews the current status of pneumococcal disease and
      pneumococcal vaccines. We also review the current situation of pneumococcal
      infections and vaccines in Taiwan. Surveillance of disease burden and clinical
      isolates should be continued.

PMID- 16422183
TI  - Pollakiuria in children with tic disorders.
AB  - BACKGROUND: To describe the rarely reported characteristics of pollakiuria in
      children with tic disorders (TD). METHODS: During a period of one year, all
      patients visiting our Tourette Syndrome (TS) Clinic with TD were studied for
      presentation of pollakiuria. RESULTS: We found that nine (1.9%) out of 467
      children with TD had pollakiuria: 407 boys and 60 girls, with a mean age of 8.7
      years. Of these nine children, there were eight boys and one girl, and their mean
      age was 7.4 years. Five had transient TD, one had chronic motor TD and the
      remaining three had TS. Their pollakiuria recovered within two to six months,
      except for two male patients aged six and 19 years, whose pollakiuria persisted
      for more than a year. Factors precipitating anxiety were identified in only three
      children. Obsessive compulsive behaviors could be traced in eight patients.
      CONCLUSIONS: Pollakiuria occurring in children with TD is not frequently
      encountered. It usually has a benign course, as it does in those without tics.
      However, sometimes the pollakiuria waxed and waned over years, as do tics.
      Pollakiuria could be a manifestation of tics or a compulsion, instead of just an
      anxiety disorder.

PMID- 16422184
TI  - Comparison of plasma interferon-gamma and antigen 60 immunoglobulin G in
      diagnosing pulmonary Mycobacterium tuberculosis infection.
AB  - BACKGROUND: An elevated interferon-gamma (IFN-gamma) level has been reported in
      the plasma of patients with pulmonary tuberculosis. Serologic diagnosis of
      tuberculosis using Antigen 60 immunoglobulin G (A60 IgG) is a well-known
      diagnostic approach. This study evaluated plasma IFN-y compared to A60 IgG in
      diagnosing Mycobacterium tuberculosis. METHODS: This study recruited 65 patients
      with tuberculosis and 59 controls. The plasma levels of A60 IgG and IFN-gamma
      were measured using enzyme-linked immunosorbent assay kits. RESULTS: The cutoff
      values of IFN-gamma and A60 IgG tests were set at 0.137 pg/ml and 261.2 units.
      The sensitivity and specificity of the IFN-gamma test were 27.7% and 91.5%. The
      positive and negative predictive values of the IFN-gamma test were 53.4% and
      78.3%. Moreover, the sensitivity and specificity of the A60 IgG test were 53.8%
      and 67.8%. The positive and negative predictive values of the A60 IgG test were
      37.0% and 80.7%. Finally, the sensitivity and specificity of the combined A60 IgG
      and IFN-gamma tests were 64.6% and 62.7%. The positive and negative predictive
      values of the combined A60 IgG and IFN-gamma tests were 37.8% and 83.4%.
      CONCLUSIONS: The combined tests did not achieve significant improvement in
      disease prediction. The A60 IgG test and IFN-gamma test had similar diagnostic
      value in pulmonary Mycobacterium tuberculosis infection.

PMID- 16422185
TI  - Effects of pelvic nerve neurectomy and estrogen on the M2 muscarinic receptor of
      the urinary bladder.
AB  - BACKGROUND: Normal physiological voiding, as well as generation of abnormal
      bladder contractions in the diseased state, is critically dependent on
      acetylcholine-induced stimulation of contractile muscarinic receptors on the
      detrusor muscle of the urinary bladder. This study investigated the effect of
      pelvic nerve neurectomy and estrogen treatment on the M2 muscarinic receptors of
      urinary bladder. METHODS: We studied the muscarinic cholinergic receptor density
      in the urinary bladder of castrated female rats following four weeks of estrogen
      treatment and/or pelvic nerve neurectomy. We used immunohistochemistry to detect
      the expression of M2 receptors on the smooth muscle cells of urinary bladder.
      RESULTS: When compared to a sham-operated group, the M2 receptors in the urinary
      bladders of rats that had undergone bilateral pelvic nerve neurectomy and
      estrogen treatment, showed no significant change. However, the M2 receptors
      decreased significantly in the urinary bladders of rats that had undergone
      simultaneous estrogen treatment and bilateral pelvic nerve neurectomy, when
      compared to the other groups (p < 0.05). CONCLUSION: Pelvic nerve denervation has
      a synergetic effect on the estrogen-induced down regulation of M2 receptor
      immunoreactive cells in the urinary bladder.

PMID- 16422186
TI  - The postpartum metabolic outcome of women with previous gestational diabetes
      mellitus.
AB  - BACKGROUND: This study investigated postpartum metabolic abnormality in women
      with previous gestational diabetes mellitus (GDM) and predictive factors for
      postpartum glucose intolerance. METHODS: From March 2001 to February 2003, 127
      prior-GDM women underwent a 75g oral glucose tolerance test (OGTT) and metabolic
      assessment at least six weeks after delivery. To identify the predictors,
      clinical variables obtained at the time of GDM were compared. RESULTS: The
      cumulative incidence rates of diabetes mellitus (DM) and abnormal glucose
      tolerance (AGT) i.e. impaired fasting glucose or impaired glucose tolerance, in
      women with previous GDM were 13.4% and 29.1%, respectively. Postpartum body mass
      index (BMI), total cholesterol, HDL cholesterol, triglycerides, blood pressure,
      waist-to-hip ratio and fasting C-peptide were not significantly different among
      DM, AGT and normal glucose tolerance (NGT) women. However, the C-peptide/glucose
      score was lower in DM than in AGT and NGT women (p < 0.01). DM or AGT women had
      higher prepregnancy BMI and fasting glucose level for 100g OGTT than NGT women (p
      < 0.05) at the time of GDM. The fasting glucose value was an independent risk
      factor. The cutoff point of three abnormal values in 100g OGTT provided 86%
      sensitivity and 43% specificity for the prediction of postpartum DM or AGT.
      CONCLUSIONS: High prepregnancy BMI and increased glycemic deterioration at the
      time of GDM are found in women developing postpartum DM and AGT. The fasting
      glucose value for 100g OGTT is an independent risk factor and more than three
      abnormal glucose values offers good diagnostic efficacy in predicting postpartum
      glucose intolerance.

PMID- 16422187
TI  - Treating colorectal polypoid neoplasms during a colonoscopy.
AB  - BACKGROUND: To evaluate the efficacy and outcomes of endoscopic treatment for
      colorectal polypoid neoplastic lesions. METHODS: From September 1999 to May 2003,
      11,447 consecutive colonoscopic examinations were performed in 9864 patients,
      totaling 5355 endoscopic polypectomies for colorectal polypoid neoplasms.
      According to the macroscopic characteristics, the neoplasms were classified into
      protruded (n = 3953) and sessile (n = 1402) ones. A snare polypectomy was
      conducted on 3987 lesions and hot biopsy forceps removal on 1368 lesions.
      RESULTS: Histological diagnoses included 4456 neoplastic lesions (4282 adenomas
      and 174 adenocarcinomas) and 899 non-neoplastic lesions (889 hyperplastic and 10
      inflamed polyps). For the adenocarcinoma group, 24 instances involved submucosal
      invasion or an unclear resection margin, and these patients received a further
      operation, while 11 surgical specimens disclosed no residual tumors. Three
      (0.05%) perforations and 96 (1.8%) instances of bleeding were found following
      endoscopic polypectomy. No procedure-related mortality was found, and no
      recurrent malignancy was found after 14 to approximately 56 months of follow-up.
      CONCLUSIONS: To lower the incidence of and mortality from colorectal cancer,
      endoscopic polypectomy for colorectal polypoid neoplasms is an effective and safe
      procedure.

PMID- 16422188
TI  - Fluorescent measurement of [Ca2+]c: basic practical considerations.
AB  - During the last decade or so, the range of fluorescent indicators for Ca2+ has
      increased dramatically, so that there are now a host of probes available. Each
      may offer particular advantages depending on the design of the experiment and the
      fluorometric equipment available. Careful choice of the indicator is therefore
      central to achieve a successful outcome. The probe that is chosen will of course
      depend on the aims of the experiment, how the indicator will be introduced into
      the cell(s), and the excitation source and detection equipment that are
      available. I hope that this chapter will not only help investigators choose the
      most appropriate indicator but, in addition, give an insight into what can be
      achieved using fluorescent Ca2+ indicators.

PMID- 16422189
TI  - Measurement of [Ca2+]i in whole cell suspensions using fura-2.

PMID- 16422190
TI  - Measurement of [Ca2+] in cell suspensions using indo-1.

PMID- 16422191
TI  - Confocal microscopy: theory and applications for cellular signaling.

PMID- 16422192
TI  - Single-cell and subcellular measurement of intracellular Ca2+ concentration.

PMID- 16422193
TI  - Ratiometric Ca2+ measurements using the FlexStation scanning fluorometer.

PMID- 16422194
TI  - Measuring Ca2+ changes in multiwell format using the fluorometric imaging plate
      reader.

PMID- 16422195
TI  - Measurement of Ca2+ entry using 45Ca2+.

PMID- 16422196
TI  - Measurement of [3H]PN200-110 and [125I]omega-conotoxin MVIIA binding.

PMID- 16422197
TI  - Whole-cell patch clamp recording of voltage-sensitive Ca2+ channel currents
      heterologous expression systems and dissociated brain neurons.

PMID- 16422198
TI  - Measurement of phospholipase C by monitoring inositol phosphates using
      [3H]inositol-labeling protocols in permeabilized cells.

PMID- 16422199
TI  - Measurement of inositol(1,4,5)trisphosphate using a stereospecific radioreceptor
      mass assay.

PMID- 16422200
TI  - Measurement of calcium fluxes in permeabilized cells using a 45Ca2+ uptake and
      release assay.

PMID- 16422201
TI  - Microinjection of myo-inositol(1,4,5)trisphosphate and other calcium-mobilizing
      agents into intact adherent cells.

PMID- 16422202
TI  - Measurement of free [Ca2+] changes in agonist-sensitive internal stores using
      compartmentalized fluorescent indicators.

PMID- 16422203
TI  - Measurement of [Ca2+]i in smooth muscle strips using front-surface fluorimetry.

PMID- 16422204
TI  - Measurement of calcium and movement in heart cells.

PMID- 16422205
TI  - Simultaneous analysis of intracellular pH and Ca2+ from cell populations.

PMID- 16422206
TI  - Measurement of cytosolic-free Ca2+ in plant tissue.

PMID- 16422207
TI  - Assay and purification of calmodulin-dependent protein kinase.

PMID- 16422208
TI  - Assay and purification of calmodulin-dependent cyclic nucleotide
      phosphodiesterase and isozyme separation.

PMID- 16422209
TI  - Measurement of Ca2+-ATPase activity (in PMCA and SERCA1).

PMID- 16422210
TI  - [Prevalence of respiratory symptoms. Currently available data on German
      practices].
AB  - Respiratory symptoms and lung function impairment as an expression of COPD are
      frequent in Germany. The symptoms, especially dyspnea, correlate only moderately
      with the degree of functional impairment. In contrast to the actual GOLD
      guidelines, in general practices the therapy is based on symptoms rather than on
      lung function, resulting in an undertreatment of asymptomatic patients.
      Therefore, increasing utilization of spirometry in practices is to demand; on the
      other hand respiratory symptoms should gain a greater significance in the GOLD
      guidelines, also against the background of disease-related costs.

PMID- 16422211
TI  - [Importance of air-trapping in patients with COPD. Pathophysiological principle].
AB  - Exertional dyspnea is the leading symptom in patients with COPD. The main causes
      are progressive weakness of skeletal muscles, reduction of diffusing capacity in
      emphysema and above all dynamic hyperinflation as a result of the collapsibility
      of bronchioli with expiratory flow limitation. The exercise-induced
      hyperinflation leads to a reduction of inspiratory capacity. Therefore, patients
      are unable to increase the minute volume under exercise. The inadequate
      ventilatory answer to an increased ventilatory drive is perceived as dyspnea. The
      inhalation of long-acting bronchodilators reduces hyperinflation and increases
      exercise capacity.

PMID- 16422212
TI  - [Bronchodilators reduce air-trapping in COPD patients].
AB  - Expiratory flow limitation, air-trapping and hyperinflation are well-known
      problems in COPD patients. Due to dyspnea during exercise COPD patients often
      avoid physical activity, which is one of the most important parameters of quality
      of life. In studies with long-acting bronchodilators, e.g., the anticholinergic
      agent tiotropiumbromide, a reduction of expiratory flow limitation,
      hyperinflation and dyspnea could be demonstrated. This was followed by an
      increase in physical activity. Increase in inspiratory capacity and reduction of
      functional residual capacity correlated well with the improvement of exercise
      capacity. In conclusion, bronchodilators such as tiotropiumbromide are able to
      reduce hyperinflation in COPD patients.

PMID- 16422213
TI  - [Optimization of therapy via rehabilitation plus pharmacotherapy].
AB  - Pulmonary rehabilitation of patients with COPD is more effective when the optimal
      bronchodilation has been reached. For obvious reasons therefore, the best
      possible bronchodilatory treatment should be instituted and subsequently, along
      with this pharmacotherapy, rehabilitation should be started. Tangible success for
      the patient can be expected from a combination of training and medication. In
      view of the relatively short-lived effects of a training therapy, it would be
      appropriate to make possible the continuous participation of the patient in
      pulmonary training through the build-up of respective networks. Those affected
      should be activated and their personal responsibility emphasized.

PMID- 16422214
TI  - [Laudatio. On the presentation of the 2005 Robert Koch Award to the drug
      tiotropium bromide (spiriva)].

PMID- 16422215
TI  - [Gratitude].

PMID- 16422216
TI  - [Low dose intravitreal triamcinolone acetonide in the treatment of neovasular
      glaucoma].
AB  - PURPOSE: To report the effect of an intravitreal injection of 4 mg of crystalline
      triamcinolone acetonide (Kenacort) as symptomatic treatment of neovascular
      glaucoma. MATERIAL AND METHODS: This clinical study is based on clinical and
      experimental investigations that examined the tolerability and the angiostatic
      effect of triamcinolone acetonide. The study includes prospectively 8 eyes of 8
      patients with neovascular glaucoma secondary to ischemic central retinal vein
      occlusion (n=8). All patients received an intravitreal injection of 4 mg of
      crystalline triamcinolone acetonide (0.1 cc) as the only procedure or in
      combination with transscleral cyclodiode as glaucoma treatment. Their mean age
      was 74.5 +/- 14.4 years. Mean intraocular pressure (IOP) was 38.9 +/- 9.3 mmHg.
      Mean follow-up was 6 months. RESULTS: 4 of 8 patients were treated by crystalline
      triamcinolone acetonide as the only procedure (n=3). Twenty seven days after
      intravitreal kenacort injection, the others four patients have been treated by
      transscleral cyclodiode (n=4) as glaucoma treatment. After injection, including
      the first postoperative day, patients report a subjective reduction of ocular
      pain. Furthermore no intra- or extraocular inflammatory reactions were observed
      during the follow-up. Intraocular pressure was significantly reduced to 18 +/-
      6.2 mm Hg at the end of the follow-up period. When considering only the four
      patients in which the intraocular cortisone injection was the only procedure
      performed, mean intraocular pressure decreased from 41.75 +/- 7.05 mm Hg to 20.5
      +/- 6.6 mm Hg. Iris neovascularisation was significantly decreased from grade IV
      to grade I in all patients at the end of the follow-up CONCLUSION: Intravitreal
      injection of 4 mg triamcinolone acetonide contributes to a better management of
      the neovascular glaucoma.

PMID- 16422217
TI  - [Traumatic cataract: clinical and therapeutic aspects].
AB  - PURPOSE: To assess clinical and therapeutic outcomes in traumatic cataracts.
      METHODS: Retrospective study of 20 cases of traumatic cataracts seen between 2001
      and 2004. Mean age at diagnosis was 35 years (5-72 yr), 25% were infants. There
      were 11 women and 9 men. Extracapsular cataract extraction was performed in
      eighteen patients (90% of cases), 13 were implanted in posterior chamber, 3
      having zonular rupture were implanted in anterior chamber. Two patients remained
      aphakic because of retinal lesions. Two patients with lens subluxation underwent
      intracapsular cataract extraction with anterior chamber implantation. The mean
      delay of surgery was 4 weeks. RESULTS: Overall satisfactory with 55% of final
      visual acuity more than 1/10. Visual acuity was better in implanted eyes, poorer
      in infants and after ocular perforation. Fibrinous uveitis was the common early
      postoperative complication especially in children. CONCLUSION: The majority of
      eyes with traumatic cataract could be safely rehabilitated after surgery and
      lensimplantation. In traumatic cataract, the vision can be severely threatened,
      preventive methods should be encouraged.

PMID- 16422218
TI  - [Post-traumatic glaucoma with irido-corneal angle injuries in Cameroon].
AB  - AIM: To study the particularities of late post-traumatic glaucoma with irido
      corneal angle injuries in black Cameroonians. MATERIAL AND METHODS: Retrospective
      analysis of 1343 files of glaucomatous patients was carried out from January 1991
      to December 2001 at the Douala General Hospital in Cameroon in Central Africa.
      Fifty seven of them had post-traumatic glaucoma. Of these 28 were secondary to
      irido-corneal angle injuries. RESULTS: The prevalence of post-traumatic glaucoma
      related to irido-corneal angle injuries in our population was 2.1%. The mean
      patients age was 45.9 +/- 18.3 years (range, 17 to 67 years). The time from
      injury to diagnosis ranged from 1 year 4 months to 7 years (median: 3.7 years).
      The follow-up period ranged from 3 months to 5 years 6 months, with a mean of 1.7
      +/- 1.9 years. The prevalence of monocular blindness was 61.9% and 81% at the
      first and last examination respectively. The mean intraocular pressure was 36.9
      +/- 13.8 mmHg (range: 22 and 66 mmHg) at the first examination and 24.3 +/- 13
      mmHg (range: 12 and 29 mmHg) at the last examination. The mean recorded cup/disc
      ratio was 0.8 +/- 0.2. It was equal to 1.0 in 61.9% of cases. Irido-corneal angle
      recession was the most common lesion (61.9%) followed by iridodialysis (38.1%)
      and cyclodialysis (14.3%). Normalization of the intraocular pressure was achieved
      with medical treatment in 23.8% and with trabelectomy in 12.3% of the cases.
      Neovascular glaucoma was found in 4.8% of the cases. CONCLUSION: The treatment of
      secondary post-traumatic open angle glaucoma is disappointing. The patients are
      young, the disease is advanced, and the compliance and follow-up are poor. The
      prevention of post-traumatic glaucoma is based on the control of ocular trauma
      and the periodic follow-up of patients with and history of non perforating injury
      of the eye.

PMID- 16422219
TI  - Myopia: more than a refractive error--LASIK and retinal dystrophies.
AB  - Three patients who had undergone laser in situ keratomileusis (LASIK) correction
      for myopia were first seen because of suboptimal visual acuity (VA) and night
      blindness and/or photophobia. After a comprehensive examination including
      psychophysical and electrophysiological tests, two of the three patients were
      shown to suffer from a progressive conerod dystrophy. The third patient had
      retinitis pigmentosa. These cases illustrate the need for in depth preoperative
      evaluation in myopic patients about to undergo LASIK when signs or problems of
      night blindness and/or photophobia are present.

PMID- 16422220
TI  - A case of secondary frosted branch angiitis in Behcet's disease.
AB  - We report a case of Behcet's disease in a pregnant woman associated with
      secondary Frosted Branch Angiitis (FBA). FBA is a rare entity characterized by a
      florid translucent retinal perivascular sheathing of both arterioles and venules,
      with variable uveitis, retinal oedema and visual loss. To our knowledge, this is
      the first published report of FBA secondary to Behcet's disease in pregnancy.

PMID- 16422221
TI  - [Purtscher's retinopathy with a favorable outcome after corticosteroids: case
      report].
AB  - Purtscher's retinopathy is a retinal vasculopathy most commonly caused by head or
      chest trauma. The most frequent signs include multiple areas of white ischemic
      infarcts and hemorrhages located in the posterior pole. Visual outcome in
      Purtscher's retinopathy is variable and there is no well defined treatment. We
      report a 8 year old child with sudden blurred vision in the right eye after head
      trauma. Ophthalmoscopy revealed multiple whitish patches and retinal hemorrhages
      predominant in the posterior pole. Megadoses of steroids were given with good
      visual response in the first three weeks, and child's vision recovered completely
      after four months despite initial severe symptomatology.

PMID- 16422222
TI  - Screening for vascular risk factors in glaucoma: the GVRF study.
AB  - PURPOSE: To determine the prevalence of vascular risk factors (VRF) in patients
      with primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and
      ocular hypertension (OH), and to evaluate their influence in the progression of
      the disease. METHODS: 269 Belgian ophthalmologists were invited to participate in
      this cross-sectional prevalence study. Using a questionnaire the following
      parameters were analyzed in patients with POAG, NTG, and OH: age, intraocular
      pressure, refraction, visual field defect, vertical cup/disc ratio, medical
      therapy, and vascular risk factors. Progression of visual field was based on
      subjective analysis of minimum three reliable automated perimetries over a period
      of minimum three years. RESULTS: 4920 patients were enrolled in the study. 75%
      had POAG, 8% had NTG, and 17% had OH. The mean age was 67 years (40-99 y.). Fifty
      three percent were female. There was a significant difference in the prevalence
      of no VRF vs. >1 VRF between the patients with OH and the patients with POAG/NTG
      (p < 0.01). Visual field progression was found in 34% of the patients with POAG
      and 46% of the patients with NTG. In the group with POAG the presence of at least
      2 and at least 3 VRF increased the risk for visual field progression with
      respectively 16% and 42% compared to patients without VRF (p = respectively 0.03
      and 0.002). CONCLUSIONS: The prevalence of VRF is significantly higher in
      patients with POAG/NTG compared to patients with OH. The presence of VRF might
      increase the risk for progression of glaucomatous visual field defects.

PMID- 16422223
TI  - Dynamic contour tonometry (DCT) versus non-contact tonometry (NCT): a comparison
      study.
AB  - In a prospective study we measured the intraocular pressure (IOP) by means of a
      Non-Contact Tonometer (NCT) and by means of a Pascal Dynamic Contour Tonometer
      (DCT), and the Central Corneal Thickness (CCT) by means of a contact pachymeter
      in 294 emmetropic or ametropic eyes. There is a linear relation between NCT and
      CCT. This linear relation doesn't exist between DCT and CCT. The same
      measurements were done before and 6 weeks after a Lasik intervention in 58 myopic
      eyes. Lasik intervention influences NCT but doesn't influence DCT.

PMID- 16422224
TI  - Comparison between arthroscopy and arthrotomy in the treatment of shoulder
      instability.
AB  - Anterior post-traumatic shoulder instability represents a common finding in
      orthopaedic surgery. The surgical treatment of this lesion is often indispensable
      for the normal social life of the patient and for the sports activity of the
      young. The Bankart procedure with capsular retensioning by arthrotomic access has
      for years been the gold standard. In the last 10 years arthroscopic accesses have
      gained more and more consent for the surgical treatment of such lesions, with
      results that have considerably improved in time. It is the purpose of this study
      to compare the results obtained in patients affected with anterior-inferior post
      traumatic shoulder instability treated by Bankart surgery, arthrotomic and
      arthroscopic, with a minimum follow-up of 4 years.

PMID- 16422225
TI  - The inverse prosthesis as a revision prosthesis in failures of shoulder
      hemiarthroplasty.
AB  - The authors describe their series of seven cases of complications and failures of
      shoulder hemiarthroplasty that were submitted to revision surgery involving an
      inverse prosthesis. This prosthesis has for some time now been indicated in
      elderly patients with arthropathy caused by rupture of the cuff. In our cases
      this prosthesis was implanted in patients who had undergone shoulder
      hemiarthroplasty for fracture and for arthrosis. The Constant score was used for
      pre- and postoperative evaluation. Results at mid-term, from 2 to 4 years,
      indicate evident improvement in Constant score that rose from a mean of 23.14
      preoperatively to a mean of 49.14 postoperatively. Despite the limited follow-up
      the authors suggest the use of the inverse prosthesis as an effective alternative
      solution in shoulder arthroplasty revision surgery.

PMID- 16422226
TI  - Bone with cement and antibiotic: antibiotic release in vitro.
AB  - It was the purpose of the study to evaluate morcellized bone with cement and
      antibiotic release mixed with vancomycin and methylmethacrylate cement (PMMA).
      The aim of the study is part of a wider one aimed at verifying the possibility of
      using this composite for the treatment of chronic septic pathologies of the bone.
      Five cylinders 1 cm in height by 1 cm in diameter, formed by morcellized bone
      with cement and vancomycin were immersed in plasma and 5 in physiological
      solution. Three cylinders equal in size but formed by cement and antibiotic alone
      were immersed in plasma and 3 in physiological solution. All of the cylinders
      remained in immersion for 28 days at a temperature of 37 degrees C. The immersion
      fluids were changed every day during the first week and on days 14, 21 and 28.
      The quantity of vancomycin released was dosed in each specimen. The greatest and
      most constant release of antibiotic took place in the cylinders of morcellized
      bone, cement and antibiotic immersed in plasma.

PMID- 16422227
TI  - In vivo study on critical defects using the sheep model.
AB  - Bone grafting procedures are widely used to repair large defects successfully in
      humans, but new surgical therapies can be designed to improve allograft
      integration. The objective of this study was to investigate the best surgical
      procedure to study bone graft integration in a large animal model. An
      osteoperiosteal defect of 3 cm in the tibia or in the metatarsal was made in 15
      adult crossbreed sheep to investigate osteo-integration of a homologous bone
      graft in an intercalary critical defect. DCP plates, alone or in association with
      Scotchcast or external fixator were used as fixation devices. The Scotchcast as
      was applied after surgery and left for 2 months to avoid torsion stress of the
      limb during the stand up movement. Metatarsal defect fixed with 7-hole DCP plate
      and protected with Scotchcast was the best surgical approach to avoid early or
      late implant failures, and provided good radiographic results after 4 months.

PMID- 16422229
TI  - Current trends in periprosthetic hip fractures: a review of the literature and an
      analysis of three clinical cases.
AB  - It is the purpose of this study to review current trends and guidelines in the
      treatment of periprosthetic hip fractures, and to report three cases of patients
      operated on and treated by different types of instrumentation: Modified Mennen
      plate by De Puy, Dall-Miles trochanteric grip, Zimmer cable-ready plate.

PMID- 16422228
TI  - Nonsurgical treatment of multiple vertebral fractures. Clinical case review of
      the literature.

PMID- 16422231
TI  - Stiff-skin syndrome.
AB  - It is the purpose of this paper to present the case of a patient who came to our
      observation because of the occurrence of non-elastic hardening of the skin (stone
      hard skin) and of the subcutaneous tissue that began during early childhood. The
      parents reported having observed the gradual functional limitation of numerous
      joints with asymmetrical distribution, more evident in the elbow and the right
      scapulohumeral joint. There were no signs of involvement of the internal organs;
      hematologic testing was normal. Described for the first time in 1971 by Esterly
      nd McKusik and called stiff skin syndrome (SSS), this is a rare genetic
      alteration characterized by hardening of the skin and subcutaneous tissue
      associated with gradual joint stiffness and, at times, hirsutism. Generally,
      there are no modifications in the internal organs or in the musculoskeletal
      structures; anomalies of the immune system are not described. Modifications are
      manifested during early childhood causing gradual functional limitation of the
      hips and knees, with consequent difficulty related to posture and walking.
      Deficit in the upper limbs is less important. The literature describes about 25
      cases with little incidence of familiarity; etiopathogenesis is unknown.

PMID- 16422230
TI  - Compression of the lower branch of the suprascapular nerve by a cyst: description
      of a case and review of the literature.
AB  - Ganglion cysts responsible for compression syndrome of the lower branch of the
      suprascapular nerve are described, but they are rare. The authors describe a well
      documented case that was treated in a traditional manner by exeresis conducted
      through posterior access. Pain was relieved immediately, while force in external
      rotation and electromyographic findings improved as early as two months after
      surgery. One year after surgery the patient does not complain of the recurrence
      of symptoms. The literature is analyzed and therapeutic options available are
      discussed.

PMID- 16422232
TI  - Osteoid osteoma of the femur with a double nidus: a case report.
AB  - Osteoid osteoma is a common benign lesion, that occurs in children and young
      adults. The authors report the observation of a multifocal lesion which is
      infrequently reported in the literature. S.A., a 10-year-old female came to our
      observation complaining of spontaneous pain in her right hip and cruralgia
      radiating to the homolateral knee over the last 6 months; the symptoms, which
      increased during the night, were relieved by treatment with NSAIDS. Clinical
      examination and imaging studies confirmed a diagnosis of osteoid osteoma with a
      double nidus; the lesion was treated by CT-guided thermo-ablation with
      radiofrequency under general anaesthesia. Complete regression of symptoms was
      observed at 2-year follow-up.

PMID- 16422233
TI  - Diagnosis, classification and treatment of partial-thickness rotator cuff tears.
AB  - Partial-thickness rotator cuff tears are a challenge for shoulder surgeons. There
      is still no standard treatment protocol. The recent introduction of new
      arthroscopic techniques and a better grasp of pathogenic mechanisms along with a
      greater functional demand from patients, have led to the need for a thorough
      analysis of the problem. This paper analyses the literature in order to simplify
      the approach to treating partial-thickness rotator cuff tears.

PMID- 16422234
TI  - Clinical and ultrasound results after arthroscopic repair of the rotator cuff.
AB  - The literature reports good functional results obtained with arthroscopic repair
      of the rotator cuff, but the incidence of anatomical healing has not been
      sufficiently studied. Ultrasound examination makes it possible to accurately
      document the healing process of the tendon at the bone, gathering information
      that may be useful in a comparison with clinical data. A total of 43 consecutive
      arthroscopic repairs of rotator cuff injuries were considered, that had made use
      of anchors and non-resorbable suturing. A total of 42 patients were willing to
      undergo clinical monitoring with an associated ultrasound examination after 3, 6
      and 12 months. When ultrasound examination after 6 and 12 months was carried out,
      36 patients presented with anatomical healing of the rotator cuff. The total
      percentage of repair failures was 14.3% and increased to 23% if we take into
      consideration the subscapular tendon alone. Constant score went from a
      preoperative mean of 51.25 to a mean of 78.21 after 12 months (p<0.001).
      Arthroscopic repair of the rotator cuff leads to anatomical healing of the
      tendons in a high percentage of cases, obtaining good functional results. The
      absence of healing is associated with lower values for recovery of strength at
      clinical follow-up. The advanced age of the patients (p<0.001) and the extensive
      injuries that involve several tendons (p=0.002) are negative prognostic factors.

PMID- 16422235
TI  - Algorithm for the treatment of calcific tendinitis in the rotator cuff:
      indications for arthroscopy and results in our experience.
AB  - Calcific tendinitis of the rotator cuff is a relatively frequent pathology and at
      times, in some phases, it is a disabling one: for this reason, numerous
      therapeutic options have been proposed. The authors propose an algorithm for the
      classification and treatment of calcific tendinitis and report their experience
      with arthroscopic treatment over a three-year period from 2001 to 2004. Based on
      the algorithm proposed, out of a total of 126 shoulders affected with calcific
      tendinitis of the rotator cuff for which debridement was indicated, 106 us-guided
      percutaneous surgeries (EPT), and only 20 arthroscopies were performed.
      Arthroscopy is indicated, on the basis of the algorithm that we followed, in
      patients affected by chronic and persistent calcific tendinitis who did not
      benefit from the execution of previous types of non-surgical treatment for a
      period of at least 6 to 12 months. Shoulder instability was found to be present
      in 8 patients out of 20 treated arthroscopically. After arthroscopy, short- and
      medium-term results were always positive with the exception of one case that
      evolved into adhesive capsulitis. Based on an analysis of this series, we were
      able to confirm the usefulness and clinical applicability of an algorithm to
      classify and treat calcific tendinitis of the rotator cuff; we also confirmed the
      role of arthroscopic treatment that in cases which did not respond to
      conservative procedures proved to be effective in resolving symptoms.

PMID- 16422236
TI  - Comparative and experimental study on different tendinous grasping techniques in
      rotator cuff repair: a new reinforced stitch.
AB  - Arthroscopic repair of wide rotator cuff ruptures is burdened by a percentage of
      recurrences that is greater than the repair carried out when an open technique is
      used. One of the main reasons for this difference can be searched for in the
      minor hold of stitching on the tendinous aspect obtained with arthroscopic
      repair. In fact, when an open technique is used, good hold can be guaranteed by
      using reinforced stitches such as the modified Mason-Allen. Thus, arthroscopic
      repair technique on the tendinous aspect, particularly in wide and massive
      injuries, must be improved. It was the purpose of this study to compare a new
      reinforced stitch that can easily be obtained in arthroscopy (simple stitch that
      orthogonally crosses a horizontal stitch previously knotted on the tendon: SS
      HL), with traditional stitches (simple stitch, mattress-stitch and modified Mason
      Allen stitch). Tests were carried out on sheep infraspinatus tendons in order to
      evaluate the resistance of pull-out. The SS-HL stitch showed resistance to
      loading that was similar to that when the modified Mason-Allen was used, but it
      was greater than that shown by the simple stitch (+48%) and the mattress stitch
      (+35%).

PMID- 16422237
TI  - Transplant of the teres major in the treatment of irreparable injuries of the
      rotator cuff (long-term analysis of results).
AB  - Purpose of this study is to evaluate the effectiveness of muscle transfer of the
      teres major in the treatment of irreparable posterosuperior injuries of the
      rotator cuff. Long-term monitoring of the results obtained in 20 patients treated
      at our clinic using this method are reported, comparing the data obtained in
      evaluations of results with preoperative values. Clinical evaluations were
      obtained using the Constant Score System, while X-ray examination showed the
      presence of osteoarticular modifications, and MRI and electromyography the
      preserved morphology and function of transplant. The mean Constant Score
      increased from 31.6 points preoperatively to 66.1 points postoperatively at the
      time of follow-up. At follow-up, MRI allowed us to evaluate any fatty
      degeneration of the muscle fibers of transfer and the integrity of tendinous
      insertion on the humeral greater tuberosity. The obtained results allowed us to
      reveal the advantages and the disadvantages of teres major transplant in
      irreparable posterosuperior ruptures of the cuff.

PMID- 16422238
TI  - Oblique capsular shift in anterior and anteroinferior shoulder instability.
AB  - Patients submitted to oblique capsular shift were followed-up; this is a personal
      method used to treat recurrent anterior and anteroinferior dislocation of the
      shoulder. A total of 186 patients were followed-up. The results were good as
      there were no recurrences, recovery of shoulder movement was early and ample, and
      the Constant score was about 81.2.

PMID- 16422239
TI  - Anterior-inferior shoulder instability: treatment based on the Thal method.
AB  - Purpose of this study is to analyze the results of a consecutive series of 139
      patients affected with anterior-inferior shoulder instability and treated by
      arthroscopic capsuloplasty using the Thal method with absorbable and non
      absorbable Mitek knotless anchors. Much attention was paid to the preoperative
      and intraoperative selection of patients, excluding from the arthroscopic
      procedure those with bony Bankart lesions measuring more than 25%, with an
      inverted-pear glenoid, with engaged Hill-Sachs lesions and patients with HAGL
      lesions. Pre- and postoperative clinical evaluation was carried out using the
      Rowe scale. Scores rose from 45-55 to 96 postoperatively. Intra-articular
      mobilization of the anchors did not occur and peri-metallic lysis was not
      manifested. Areas of bone resorption were observed in 7 cases (7/38, 18.4%) with
      the presence of peri-insertional geodes with biological anchors, but this had no
      effect on the clinical results.

PMID- 16422240
TI  - How to identify and calculate glenoid bone deficit.
AB  - In recent years, we have seen increased interest in bone lesions of the glenoid
      rim as acute fractures (Bony-Bankart) and as chronic bone defect in instability.
      This derives from three main clinical and statistical findings: a significant
      incidence of bony Bankart lesion after a first dislocation, a high percentage of
      glenoid bone defects in chronic instability, and, finally, a close relationship
      between bone defect and incidence of recurrence after arthroscopic stabilization.
      The authors agree on determining glenoid bone defect that exceeds 15-20% as the
      main contraindication to arthroscopic stabilization. It is thus necessary to
      accurately calculate bone defect in order to be able to plan the most suited type
      of surgery. The authors report their simple, accurate and reproducible CT method
      known as Pico to quantify and measure bone defect in terms of percentage bone
      area and in terms of square mm of defect.

PMID- 16422241
TI  - Injury of the axillary nerve subsequent to recurrence of shoulder dislocation.
      Clinical and electromyographic study.
AB  - Injuries of the axillary nerve subsequent to recurrence of glenohumeral
      dislocation have received only minimal attention. It is the purpose of this study
      to define the prevalence and the progression in time of injury of the axillary
      nerve in patients with recurrence of anterior shoulder dislocation. For two years
      we observed a total of 185 patients who had had primary shoulder dislocation.
      Excluded from the study were patients who had fractures associated with metabolic
      disorders that favored neurologic deficit. During the period of study, 98
      patients contacted us again after recurrence of the dislocation: there were 89
      patients aged over 60 years and 9 aged below 60 years. All of the patients were
      evaluated clinically and submitted to EMG in order to verify the condition of the
      axillary nerve. Four patients (4%) had neuroapraxia of the axillary nerve. One of
      these also had neuroapraxia of the radial nerve. Of the four patients, one was a
      male aged 34 years; the others were all aged over 60 years. In all of the cases,
      function of the axillary nerve completely recovered after a mean period of 4
      months (3-5.3 months) after recurrence. Injury of the axillary nerve can occur at
      the time of the first recurrence of the injury. However, prevalence is
      significantly lower than that observed after primary dislocation. The occurrence
      of this injury should be taken into consideration, particularly in elderly
      patients, in order to avoid erroneous clinical diagnosis and massive rupture of
      the cuff subsequent to recurrence of the dislocation.

PMID- 16422242
TI  - Surgical treatment of sequelae of fractures of the proximal third of the humerus.
      The role of osteotomies.
AB  - Between 1996 and 2003 a total of 19 humeral head osteotomies were performed to
      treat post-traumatic malunion of the proximal humerus. Mean age was 46 years,
      ranging from 17 to 71 years. The period of time between traumas and surgeries
      ranged from 6 to 22 months. Osteotomy procedure was as follows: one after two
      part fracture of the greater tuberosity, three after two-part fracture of the
      surgical neck, five after three-part fracture of the greater tuberosity, eight
      after four-part fracture, two after complex head splitting fracture, one after
      two-part fracture with anterior dislocation. Three different types of osteotomies
      were performed: osteotomy of the humeral neck for varus deformity, isolated
      osteotomy of the greater tuberosity, and a new osteotomy technique (two-plane and
      three-plane osteotomy) for three- and four-fragment fracture sequelae. At the
      time of follow-up evaluation, all 19 patients were questioned regarding pain and
      function. Excellent results in 14 patients and satisfactory results in 5 were
      obtained. None of the patients required revision surgery. Findings were recorded
      using the Constant rating scale. All patients had had significant pain relief
      after shoulder osteotomy. Range of motion was increased in all patients treated
      by osteotomy. The success of osteotomy in these cases was based on: patient
      selection, extensive preoperative evaluation, surgical technique and
      postoperative rehabilitation.

PMID- 16422243
TI  - Treatment of fractures of the humeral head by cemented and cementless
      hemiarthroplasty. Our experience.
AB  - Patients submitted to shoulder hemiarthroplasty for the treatment of fracture of
      the humeral head were analyzed. The study was conducted from 1991 to June 2001
      using 2 different prosthetic models: the Neer cemented prosthesis and the
      Randelli cementless prosthesis. The authors were able to evaluate 93 cases out of
      148 operated on. A review of data revealed the essential importance of
      reconstruction of the tuberosity and rehabilitation. It was also observed that
      the age of the patient and the severity of the fracture did not in any way
      influence results. X-ray examinations did not shed light on loosening phenomena
      in prosthetic implants. Erosion of the glenoid was observed only when two factors
      coexisted: incorrect position of the prosthesis and low mobility of the shoulder.
      The study allowed us to reveal numerous prognostic elements, both favorable and
      adverse, and to measure their importance and priority.

PMID- 16422244
TI  - Partial prosthetic replacement of the shoulder in fractures and fracture
      dislocations of the proximal humerus.
AB  - A total of 48 patients submitted to partial shoulder replacement for fracture and
      fracture-dislocation of the proximal humerus were evaluated after a mean follow
      up of 5.2 years (range 2 to 10 years). The absolute mean Constant score was 57.8,
      relative score 76.8% and corrected score 80.4%. A mean of 8.8 points were
      totalled in the Simple Shoulder Test. Out of 45 patients evaluated
      radiographically, tuberosity consolidation in the anatomical site was evident in
      25 shoulders (55%) and the subacromial space appeared to be preserved in 20
      shoulders (44%). More than 90% of the patients declared that he or she was
      satisfied with treatment. A comparative study on subgroups of patients in an
      attempt to identify the prognostic value of several factors was conducted. Better
      functional results were obtained in subjects aged under 70 years, in fracture
      dislocations, in shoulders with whole rotator cuffs, in patients with dedicated
      modular prostheses.

PMID- 16422245
TI  - Arthroscopic neurolysis of the ulnar nerve at the elbow.
AB  - Cubital tunnel syndrome is a frequent form of neuropathy caused by entrapment of
      the upper limb. Conservative treatment and physical therapy are the treatment of
      choice for at least 6 months prior to any type of surgery. The surgical
      techniques proposed for treatment of this syndrome include simple decompression,
      transposition and neurolysis. It is the purpose of this study to demonstrate the
      advantages of arthroscopy for neurolysis of the ulnar nerve at the elbow in a
      specific cohort of patients. The patients were evaluated preoperatively and
      postoperatively based on subjective (VAS) and objective (Bishop and Dellon)
      scales. The degree of patient satisfaction on the average was more than 60%. The
      mean increase in Bishop score was 5 points (minimum 3, maximum 7). Results
      appeared to be good and stable at 6 and 12-month follow-up evaluation.

PMID- 16422246
TI  - Reverse HAGL: a possible complication of a tight anterior gleno-humeral
      stabilization.
AB  - Recently the posterior humeral avulsion of the glenohumeral capsule (Reverse HAGL
      or RHAGL) has been reported in the orthopaedic literature as another possible
      cause of posterior traumatic shoulder instability. In the present paper we
      describe three patients in whom a RHAGL was probably a consequence of a tight
      open anterior shoulder stabilisation. The main complaint of these patients was a
      stiff shoulder after an open anterior stabilisation. A progressive and worsening
      discomfort was reported by patients in spite of an accurate rehabilitation
      program. At persistence of symptoms arthroscopy was performed with evidence of
      RHAGL that was repaired in association with an anterior release. Clinical and
      functional improvement was observed but the final outcome seems to be related to
      range of motion recovery and not only to the posterior repair.

PMID- 16422247
TI  - T-cell response of advanced aids patients after highly active antiretroviral
      therapy.
AB  - OBJECTIVE: To investigate the response on late stage Chinese AIDS patients after
      highly active antiretroviral therapy (HAART). METHODS: From October 2002 to March
      2004, 20 cases of late stage Chinese AIDS patients were selected to participate
      in this opened and randomised study, we purposely chose those with CD4+ T cell
      counts <100/mm3. All of them had one or two opportunistic infections and none had
      been treated with anti-HIV drugs. All patients were tested with CD4+ (naive CD4+
      T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-),
      CD8+ T cell, plasma HIV viral load, and clinical manifestations on before,
      during, and after HAART (5 different regimes) on 1, 3, 6, 9, and 12 months.
      RESULTS: Before HAART mean CD4+ T cell counts were 32 +/- 31 (range 2-91)/mm3,
      and plasma HIV viral load were 5.07 +/- 0.85 (range 2.04-5.70) log copies/mL. In
      1 month's time patients treated with HAART had mean CD4+ and CD8 T cell counts
      increasing rapidly. After 1 month the increasing speed turned to slow down, but
      HIV viral load decreased predominantly within the first 3 months. The major part
      of increasing CD4+ T cells were memory CD4+ T cells, as fol naive CD4+ T cells
      increasing low and slow. Clinical symptoms and signs improved, and opportunistic
      infections reduced. The quality of life will be far much better than before. Each
      patient was followed for 12 months, and had finished 12 months' HAART.
      CONCLUSION: This is the first report in China that late stage Chinese AIDS
      patients after HAART could have their immune reconstitution. The regular pattern
      is similar to what had been reported in Western countries and also in China. So
      it is worth to treat late stage Chinese AIDS patients with HAART.

PMID- 16422248
TI  - Effects of transcranial magnetic stimulation on motor cortical excitability and
      neurofunction after cerebral ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: To clarify the effects of repetitive transcranial magnetic stimulation
      (rTMS) on rat motor cortical excitability and neurofunction after cerebral
      ischemia-reperfusion injury. METHODS: After determined awake resting motor
      threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague
      Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion
      injury, then rTMS were applied to rTMS group (n=10) at different time, while
      control group (n=10) received no stimulation. A week later, MT and MEPs were
      evaluated again, as well as neurological deficits and infarct volume. The effects
      of rTMS and MCAO reperfusion injury on these parameters were analyzed. RESULTS:
      After MCAO reperfusion, both MT level and neurological deficit scores increased,
      distinct focal infarction formed, and latency of MEP elongated. Compared with the
      control group, the increased extent of MT and neurological scores of rats
      receiving rTMS were significantly lower (P < 0.05), as well as the infarct
      volumes reduced significantly (P < 0.05). But MEP was not affected by rTMS
      obviously. There was a positive linear correlation between postinjury MT and
      infarct volume (r = 0.64, P < 0.05). CONCLUSION: rTMS may facilitate
      neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could
      provide prognostic information after MCAO reperfusion injury.

PMID- 16422250
TI  - Allele distribution of five X-chromosome short tandem repeat loci in Ewenke
      population of north China.
AB  - OBJECTIVE: To study the allele genetic polymorphism of five short tandem repeat
      (STR) loci on X-chromosome in Ewenke population of north China and to provide
      basic data for forensic identification. METHODS: Genomic DNA was extracted from
      EDTA-whole blood of Ewenke population by Chelex-100. The DNA samples were
      amplified by PCR and were analyzed by polyacrylamide gel electrophoresis and
      silver staining. The sequence length variations of DXS6799, DXS8378, DXS101,
      HPRTB, and DXS6789 loci on X-chromosome in 98 unrelated Ewenke individuals were
      investigated. RESULTS: All five loci analyzed showed high polymorphism and
      genetic stability. The data of the five X-chromosome STR loci in Ewenke ethnic
      group of China was in accordance with Hardy-Weinberg equilibrium by Chi-square
      test. CONCLUSION: Allele polymorphism of five X-chromosome STR loci can be used
      as a genetic marker for forensic identification and population genetic research.

PMID- 16422249
TI  - Effect of losartan on slowing progression of chronic allograft nephropathy.
AB  - OBJECTIVE: To investigate the effects of losartan, a specific angiotensin II
      receptor blocker, on slowing progression of renal insufficiency in patients with
      biopsy-proven chronic allograft nephropathy (CAN) and the molecular mechanism of
      the therapy. METHODS: Twenty-two renal transplant recipients with biopsy-proven
      CAN (group A) were treated with losartan within two months after renal
      dysfunction for at least one year. Losartan was administered at a dose of 50
      mg/d. Twenty-four recipients in the same fashion (group B) who never received
      angiotensin II receptor antagonist were studied as control. The investigation
      time for each patient lasted one year. Renal functions and concentrations of
      plasma and urine transforming growth factor-beta1 (TGF-beta1) were compared
      between the two groups at the initiation and end of the study. In group A,
      expressions of TGF-betal mRNA and immunofluorescence intensity of TGF-betal
      protein and pathological alterations in renal biopsy specimens were compared
      between before losartan therapy and after one year of the therapy. RESULTS: At
      the initiation of the investigation, no significant differences were found
      between group A and group B in clinical data such as donor age, cold-ischemia
      time, HLA mismatch, levels of creatinine clearance (Ccr), plasma and urine TGF
      beta1 concentrations. One year later, 14 of 22 (63.6%) patients showed stable or
      improved graft functions in group A, and 4 of 24 (16.7%) in group B. The
      difference was significant (P < 0.05). At the end of the study, urine TGF-betal
      concentration was 273.8 +/- 84.1 pg/mg x Cr in group A and 457.2 +/- 78.9 pg/mg x
      Cr in group B. During one year study period, loss of Ccr was 6.6 +/- 5.4 mL/min
      in group A and 16.2 +/- 9.1 mL/min in group B. Both of the differences were
      significant between the two groups (P < 0.01). No significant differences were
      found in plasma TGF-betal concentrations between the four values determined at
      the initiation and end of the study in the two groups (F = 2.56, P > 0.05). After
      one year losartan therapy, group A showed a significant decrease in expressions
      of TGF-beta1 mRNA and TGF-betal protein in renal biopsy specimens [from 1.59 +/-
      0.35 to 0.96 +/- 0.27 and from (10.83 +/- 2.33) x l0(6) to (6.41 +/- 1.53) x
      10(6), respectively; both P < 0.01], but in light microscopy the histological
      changes were similar to the first renal biopsy. Losartan was excellently
      tolerated in all patients in group A. No cases with losartan therapy showed too
      low blood pressure and other side effects. CONCLUSION: This study suggests that
      losartan have an effect on slowing progression of CAN. Reducing production of
      intrarenal TGF-betal may play a decisive role in the efficacy of losartan.

PMID- 16422251
TI  - Changes of p38 mitogen-activated protein kinase and apoptosis after spinal cord
      injury.

PMID- 16422252
TI  - Cervical cytological screening and management in pregnant and postpartum women.
AB  - OBJECTIVE: To examine and follow up cervical cytology of pregnant and postpartum
      women and study their cytopathologic characteristics, so as to determine
      screening and managing programs for abnormal cervical cytology. METHODS: Totally
      5296 patients in pregnancy and postpartum, in which 3729 by computer-assisted
      cytology test and 1567 by liquid-based monolayers cytology test, were examined
      and diagnosed by the Bethesda System made in 2001. Those proven epithelial
      abnormalities patients were followed up until the lesions regressed to normal.
      The remaining patients, who exhibited persistent abnormalities or progression,
      were given further examinations. RESULTS: The positive rate of cervical
      cytological test was 8.72% (462/5296), including squamous carcinoma (SCA) 1 case
      (0.02%), high grade squamous intraepithelial lesion (HSIL) 34 cases (0.64%), low
      grade squamous intraepithelial lesion (LSIL) 145 cases (2.74%), atypical
      glandular cells (AGC) 5 cases (0.09%), atypical squamous cells cannot exclude
      HSIL (ASC-H) 14 cases (0.26%), atypical squamous cells of undetermined
      significance (ASC-US) 263 cases (4.97%). The 419 proven cytological abnormality
      cases were followed up successfully. The total transnegative rate in three months
      was 73.74% (309/419), in which 303 cases (72.32%) persisted normal status for
      more than six months after regression. And the transnegative rate of ASC-US, ASC
      H, AGC, LSIL, and HSIL were 79.56%, 64.29%, 100%, 72.14% and 44.12%,
      respectively. Forty-six cases received biopsy directed by colposcopy. The
      distribution of coincidence of cytopathologic and histopathologic diagnosis was:
      SCA 1 case (100%), HSIL 10 cases (76.92%), LSIL 13 cases (65%), ASC-H 2 cases
      (50%), ASC-US 3 cases (37.50%), total 29 cases (63.04%). CONCLUSIONS: We should
      cast more attention to screening cervix lesions in pregnant and postpartum women.
      Their cytopathologic characteristics are liable to make the clinician give a
      false positive diagnosis. So we propose to follow up them closely and to lower
      the indication of biopsy.

PMID- 16422253
TI  - Relationship of homocysteine and gene polymorphisms of its related metabolic
      enzymes with Alzheimer's disease.
AB  - OBJECTIVE: To investigate the relationship of plasma homocysteine (Hcy) levels
      and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase
      (MTHFR), cystathionine beta-synthase (CBS) with Alzheimer's disease (AD).
      METHODS: Plasma Hcy levels were measured by means of high voltage capillary
      electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4
      of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD
      patients and 102 non-AD controls. All controls were excluded from
      cardiocerebrovascular disorders and other diseases. RESULTS: The plasma Hcy level
      in AD patients (16.04 +/- 3.84 micromol/L) was significantly higher than that in
      the controls (11.94 +/- 3.87 micromol/L, P < 0.001). There were no significant
      differences of the genotype and allele frequencies of MTHFR C677T mutation and
      CBS 844ins68 mutation between the patients and controls. However, the T allele of
      MTHFR gene was found to relate with the plasma Hcy level increase in all
      subjects. CONCLUSION: The elevated plasma Hcy level in AD patients is probably
      involved in the pathogenesis of AD, which may be due to the environmental factor
      rather than genetic factors of the mutations of MTHFR and CBS.

PMID- 16422254
TI  - Simultaneous anterior and posterior hemivertebra resection in the treatment of
      congenital kyphoscoliosis.
AB  - OBJECTIVE: To evaluate the efficacy of simultaneous anterior and posterior
      hemivertebra resection in the treatment of congenital kyphoscoliosis caused by
      fully-segmented hemivertebra. METHODS: Twenty-one consecutive cases with
      congenital kyphoscoliosis, which were 8 males and 13 females, underwent one-stage
      operation of anterior hemivertebra resection and posterior instrumentation. All
      of the hemivertebra were fully-segmented. The average age at surgery was 11.4
      (range, 1.5-16) years old. RESULTS: The average follow-up was 23 (range, 6-50)
      months. The average Cobb's angle of the coronal curve was 51.4 degrees (30
      degrees - 120 degrees) before surgery, 16.9 degrees (0 degree - 54 degrees) after
      surgery, and 19.5 degrees at latest follow-up. The angle of segmental kyphosis
      was 37.1 degrees (0 degree - 95 degrees) before surgery and 16.1 degrees (0
      degree - 48 degrees) after surgery, and 18.2 degrees at latest follow-up. Apical
      translation was improved from 4.7 cm to 1.9 cm. The average fusion segments were
      4.8 (range, 2-10) segments. Complication included pressure sore in one case,
      pedicle cutting by pedicle screw in one case and elongation of the curve in one
      case. There was no obvious pseudarthrosis, decompensation, and kyphosis deformity
      aggravation at latest follow-up. CONCLUSION: One-stage hemivertebra resection has
      a good result in the surgical treatment of congenital kyphoscoliosis caused by
      fully-segmented hemivertebra, and may shorten fusion levels if performed at an
      earlier age.

PMID- 16422255
TI  - Clinical analysis of primary malignant melanoma of the cervix.
AB  - OBJECTIVE: To investigate the clinical and pathological characteristics of
      primary cervical malignant melanoma, and its prognosis. METHODS: The clinical and
      pathological data of four patients with primary malignant melanoma of the cervix
      were analyzed retrospectively. Nerve tissue protein S-100 and monoclonal antibody
      to melanoma (HMB-45) were measured in all cases by immunohistochemical method.
      All four patients received radical hysterectomy. Three of them received
      chemotherapy preoperation or postoperation, and one of them received biotherapy
      with interferon-gamma and interleukin-2 at the same time. All the cases were
      followed up. RESULTS: The average age of four patients was 45 years. Clinical
      symptoms presented with irregular vaginal bleeding, postcoital bleeding, or
      increase of vaginal discharge. Gynecologic examination showed polypus papilla
      cauliflower-shaped or nodulated black-brown or black-blue mass on the cervix. All
      the four cases were pathologically diagnosed with cervical malignant melanoma. S
      100 and HMB-45 were positive in all patients. Two patients died at 6 and 41
      months postoperation, respectively. The other two patients survived for 3.5 and 7
      years postoperation, respectively. CONCLUSIONS: S-100 protein and HMB-45 play
      very important roles in the diagnosis of primary malignant melanoma of cervix.
      Radical hysterectomy, chemotherapy combined with dimethyl triazemo imidazole
      carboxamide and biological therapies may improve the prognosis of the primary
      malignant melanoma of cervix if the disease could be diagnosed in an early stage.

PMID- 16422256
TI  - Forced-air warming and fluid warming minimize core hypothermia during abdominal
      surgery.
AB  - OBJECTIVE: To evaluate the effect of intraoperative combined forced-air warming
      and fluid warming system on patient's core temperature, blood loss, transfusion
      demand, extubation time, and incidence of postoperative shivering. METHODS: Forty
      patients with American Society of Anesthesiologists physical status I and II,
      aged 18-70 years, scheduled for elective abdominal surgery were randomly assigned
      to receive intraoperative warming from a forced-air blanket and fluid warming
      system or conventional cotton blanket, 20 in each group. The core temperature was
      recorded every 20 minutes during the operation, as well as the blood loss, blood
      transfusion, extubation time, and incidence of postoperative shivering. RESULTS:
      The core temperature at the end of the surgery in the warming group was
      significantly different from that in the control group (36.4 +/- 0.4 degrees C
      vs. 35.3 +/- 0.5 degrees C, P < 0.001). Application of intraoperative warming
      significantly shortened the time between the end of the surgery and extubation (P
      < 0.01). Postoperative shivering occurred in 30% of the patients in the control
      group compared to no patient in the warming group (P < 0.01). CONCLUSION: Active
      warming with air-forced blanket and fluid warming system provides sufficient heat
      to prevent hypothermia during abdominal surgery.

PMID- 16422257
TI  - Postoperative intussusception in children: a review of 14 cases.
AB  - OBJECTIVE: To search the etiologic factor, clinical diagnosis points and
      treatment of postoperative intussusception (PI). METHODS: To retrospectively
      review the clinical materials of 14 cases with PI including the cause of disease
      and treatment. RESULTS: PI occurred within 10 days (average 4 days) after the
      primary operation. Bowel obstructive symptoms gradually emerged. One case was
      diagnosed with intussusception by sonography and received enema reduction of
      intussusception by hydrostatic pressure. Thirteen cases were performed secondary
      operation. Small intestine was main site of intussusception. Manual reduction of
      the lesion was performed in 12 cases and bowel resection and anastomosis was done
      in 1 case with bowel necrosis. CONCLUSION: PI should be suspected if child
      presents with the symptoms of ileus in early postoperative period. Abdominal
      sonography may have some value on diagnosis of PI. Operation is the first choice
      for the treatment of PI.

PMID- 16422258
TI  - Expression and switching of TH1/TH2 type cytokines gene in human gliomas.
AB  - OBJECTIVE: To study the expression and switching of Th1/Th2 cytokines gene in
      human gliomas and its effects on occurring and developing of human gliomas.
      METHODS: Interleukin (IL)-2 and interferon-gamma represent Th1 type cytokines. IL
      4, IL-6, IL-10, and IL-13 represent Th2 type cytokines. The gene expressions of
      Thl/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes, and
      glioma cell lines were detected by reverse transcription polymerase chain
      reaction (RT-PCR). The biological activity of cytokines in the supernatant of
      glioma cell lines was assayed by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The total positive rates of Th1 and Th2 type cytokines gene in human
      glioma cells were 14.77% and 75%. The total positive rates of Th1 and Th2 type
      cytokines gene in glioma infiltrating lymphocytes were 22.73% and 68.17%. There
      was obviously predominant expression of Th2 type cytokines in human glioma
      tissues, glioma infiltrating lymphocytes, and glioma cell lines. There was no
      unbalanced expression of Th1/Th2 cytokines in normal brain tissues. CONCLUSION:
      There is a predominant expression of Th2 type cytokines in human glioma cells.
      The switching of Thl/Th2 cytokines gene may play an important role in the
      occurring and developing of human gliomas.

PMID- 16422259
TI  - Detection of pathogens causing genital ulcer disease by multiplex polymerase
      chain reaction.
AB  - OBJECTIVE: To establish a multiplex polymerase chain reaction (M-PCR) assay for
      simultaneous detection of pathogens causing genital ulcer disease (GUD). METHODS:
      Based on the gene-specific region of the following pathogens: Chlamydia
      trachomatis omp1/ompb, herpes simplex virus (HSV) DNA polymerase, Treponema
      pallidum tpp47, Haemophilus ducreyi 16s rRNA, four sets of primers were designed
      and an M-PCR assay was developed to detect four pathogens in one test. The assay
      was evaluated with diagnostic result of golden standard for each pathogen.
      RESULTS: Of the 51 clinical samples, M-PCR showed slightly higher positive rate
      (47.1%) of HSV than cell culture (23.6%). Meanwhile, the positive rate of T.
      pallidum detected by M-PCR and dark-field microscopy was 19.6% (10/51) and 15.7%
      (8/51), respectively. Only one sample was positive for H. ducreyi and no sample
      was positive for C. trachomatis detected by both M-PCR assay and culture.
      CONCLUSION: This primary study indicated that M-PCR assay can simultaneously and
      rapidly detect the four etiologic pathogens causing GUD.

PMID- 16422260
TI  - Cardiac echinococcosis.

PMID- 16422261
TI  - Endophthalmitis induced by mycobacterium tuberculosis being misdiagnosed as non
      infectious uveitis.

PMID- 16422263
TI  - Final report of the safety assessment of Urea.
AB  - Although Urea is officially described as a buffering agent, humectant, and skin
      conditioning agent-humectant for use in cosmetic products, there is a report
      stating that Urea also is used in cosmetics for its desquamating and
      antimicrobial action. In 2001, the Food and Drug Administration (FDA) reported
      that Urea was used in 239 formulations. Concentrations of use for Urea ranged
      from 0.01% to 10%. Urea is generally recognized as safe by FDA for the following
      uses: side-seam cements for food contact; an inhibitor or stabilizer in pesticide
      formulations and formulations applied to animals; internal sizing for paper and
      paperboard and surface sizing and coating of paper and paper board that contact
      water-in-oil dairy emulsions, low-moisture fats and oils, moist bakery products,
      dry solids with surface containing no free fats or oil, and dry solids with the
      surface of fat or oil; and to facilitate fermentation of wine. Urea is the end
      product of mammalian protein metabolism and the chief nitrogenous compound of
      urine. Urea concentrations in muscle, liver, and fetuses of rats increased after
      a subcutaneous injection of Urea. Urea diffused readily through the placenta and
      into other maternal and fetal organs. The half-life of Urea injected into rabbits
      was on the order of several hours, and the reutilization rate was 32.2% to 88.8%.
      Urea given to rats by a bolus injection or continuous infusion resulted in
      distribution to the following brain regions: frontal lobe, caudate nucleus,
      hippocampus, thalamus plus hypothalamus, pons and white matter (corpus callosum).
      The permeability constant after treatment with Urea of whole skin and the dermis
      of rabbits was 2.37 +/- 0.13 (x 10(6)) and 1.20 +/- 0.09 (x10(3)) cm/min,
      respectively. The absorption of Urea across normal and abraded human skin was
      9.5% +/- 2.3% and 67.9% +/- 5.6%, respectively. Urea increased the skin
      penetration of other compounds, including hydrocortisone. No toxicity was
      observed for Urea at levels as high as 2000 mg/kg in acute oral studies using
      female rats or mice. No signs of toxicity were observed in male piglets dosed
      orally with up to 4 g/kg Urea for 5 days. Dogs dosed orally with 5 to 30 g/L Urea
      for 4 to 10 days had signs of toxicity, including weakness, anorexia, vomiting
      and retching, diarrhea and a decreased body temperature, which led to a deep
      torpor or coma. No significant microscopic changes were observed in the skin of
      male nude mice dermally exposed to 100% Urea for 24 h. No observable effect on
      fetal development was seen in rats and mice dosed orally with an aqueous solution
      of Urea (2000 mg/kg) on days 10 and 12 of gestation. The mean number of implants,
      live fetuses, percent fetal resorptions, mean fetal weight, and percent fetuses
      malformed were comparable to control group. A detergent containing 15% Urea was
      injected into pregnant ICR-JCl mice and dams and fetuses had no significant
      differences when compared to control animals. Urea given orally did not enhance
      the developmental toxicity of N-nitrosomethylurea. Female Sprague-Dawley rats
      injected in the uterine horn with 0.05 ml Urea on day 3 (preimplantation) or on
      day 7 (post implantation) exhibited no maternal mortality or morbidity; a dose
      dependent reduction in embryo survival was seen with preimplantation treatment.
      Urea injected intra-amniotically induces mid-trimester abortions in humans. Urea
      was not genotoxic in several bacterial and mammalian assays; although in assays
      where Urea was used at a high concentration, genotoxicity was found, many in in
      vitro assays. Urea is commonly used in studies of DNA because it causes uncoiling
      of DNA molecules. Urea was not carcinogenic in Fisher 344 rats or C57B1/6 mice
      fed diets containing up to 4.5% Urea. Exposure of normal human skin to 60% Urea
      produced no significant irritation in one study, but 5% Urea was slightly
      irritating and 20% Urea was irritating in other reports. Burning sensations are
      the most frequently reported effect of Urea used alone or with other agents in
      treatment of diseased skin. Overall, there are few reports of sensitization among
      the many clinical studies that report use of Urea in treatment of diseased skin.
      The Cosmetic Ingredient Review (CIR) Expert Panel determined the data provided in
      this report to be sufficient to assess the safety of Urea. The Panel did note
      that Urea can cause uncoiling of DNA, a property used in many DNA studies, but
      concluded that this in vitro activity is not linked to any in vivo genotoxic
      activity. Although noting that formulators should be aware that Urea can increase
      the percutaneous absorption of other chemicals, the CIR Expert Panel concluded
      that Urea is safe as used in cosmetic products.

PMID- 16422262
TI  - Effect of auricular acupuncture with low power laser on four chronic allergic
      dermatoses and serum IgE level.

PMID- 16422264
TI  - Final amended report on the safety assessment of Mink Oil.
AB  - Mink Oil, obtained from the fatty tissues of minks, is a mixture of the natural
      glycerides of 14 to 20 carbon chain fatty acids. There are 100 current reported
      uses as a hair-conditioning agent, an occlusive skin-conditioning agent, and as a
      surfactant; up to a maximum concentration of 3%. Mink Oil is manufactured by
      harvesting animal hides and scraping the fat layer from the hide. It is rendered
      and refined using high temperature processes (230 degrees F to 240 degrees F) and
      saponification to reduce free fatty acids. Analyses demonstrate that Mink Oil can
      be substantially free of impurities, including pesticides. Mink Oil does not
      absorb significant UVA or UVB radiation. In a clinical test of skin penetration,
      1 h after application, Mink Oil was detected on the skin surface of all five
      panelists; it was detected within the stratum corneum in 2/5 panelists. Mink Oil
      has an oral LD50 of > 64.0 cc/kg in albino rats. No erythema or edema was noted
      after refined Mink Oil was applied for 24 h to intact and scarified area of
      albino rabbits. A 50% dilution of a Mink Oil cream did not sensitize guinea pigs
      in a maximization test. Mink Oil was not an ocular irritant to albino rabbits.
      Clinical studies using single occlusive patches found no irritation with up to
      2.8% Mink Oil, although transient mild to no irritation was noted in two
      exaggerated-use studies. Mink Oil is used in aerosols and sprays. Although there
      are no inhalation toxicity data available on Mink Oil, the available data on
      particle sizes of cosmetic aerosols and sprays indicates diameters more than an
      order of magnitude larger than the diameter of respirable particles. Most of the
      glycerides in Mink Oil are triglycerides (glyceryl triesters), the safety of
      which has been substantiated in previous safety assessments; e.g., dermal
      absorption is nil to slight; there is little or no acute, subchronic, or chronic
      oral toxicity; dermal application was not associated with significant irritation
      or sensitization; ocular exposures were, at most, mildly irritating; most of the
      genotoxicity test systems are negative; use as vehicles in carcinogenicity
      testing of other chemicals has produced no adverse reaction; and clinical tests
      produce no irritation or sensitization reactions--but, they may enhance the of
      penetration of other chemicals. Formulators should be aware of the possible
      penetration-enhancing properties of Mink Oil. Although pesticide residues have
      been analyzed and found to be below levels of detection, the Panel is concerned
      that the available data suggesting the absence of pesticide residues in Mink Oil
      are limited. The Panel advised the industry that the total polychlorinated
      biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm,
      with not more than 10 ppm for any specific residue.

PMID- 16422265
TI  - Final amended report on the safety assessment of Octyldodecyl Stearoyl Stearate.
AB  - Octyldodecyl Stearoyl Stearate is an ester that functions as a skin-conditioning
      agent and viscosity-increasing agent. It is reported to be used in 105 cosmetic
      products at concentrations from 2% to 15%. In an isolated human skin permeation
      and penetration study, 0.005% of the applied dose permeated the skin, around 3%
      was found in the epidermis, around 1.5% was in tape stripped skin layers, and
      around 95% stayed in the material applied to the skin. A formulation having 20.6%
      Octyldodecyl Stearoyl Stearate was classified as minimally to mildly irritating
      in an in vitro ocular irritation assay. Several tests of products containing from
      7.5% to 12.7% Octyldodecyl Stearoyl Stearate using rabbits produced minimal to
      mild ocular irritation. One test of 100% Octyldodecyl Stearoyl Stearate (a trade
      compound) and another of 10% Octyldodecyl Stearoyl Stearate in corn oil using
      rabbits produced no ocular irritation. Tests using rabbits demonstrated that
      Octyldodecyl Stearoyl Stearate at use concentrations was non- to mildly
      irritating to skin; only one study reported moderate irritation. Octyldodecyl
      Stearoyl Stearate was not mutagenic, with or without S-9 activation, in an Ames
      test and did not produce a significant increase in micronucleated cells in a
      mouse in vivo study. In clinical single-insult patch tests at use concentrations,
      Octyldodecyl Stearoyl Stearate was nonirritating to mildly irritating; in a
      cumulative irritation study, it caused mild irritation. Octyldodecyl Stearoyl
      Stearate was nonsensitizing in clinical tests. Because few toxicity data were
      available on Octyldodecyl Stearoyl Stearate, summaries of data from existing
      safety assessments of related ingredients (Octyl Dodecanol, Stearic Acid, and
      Octyl Stearate) were included. Undiluted Octyl Dodecanol was nontoxic during
      acute oral and dermal studies using rats and guinea pigs. Stearic Acid was
      nontoxic to rats during acute oral studies, but caused toxicity during subchronic
      studies. Rabbits treated topically with the acid were not affected adversely, and
      mild erythema and slight induration were observed when Stearic Acid was
      administered intradermally to guinea pigs and rabbits. Octyl Stearate had very
      low acute oral toxicity in rats and mice. Octyl Dodecanol produced only transient
      mild ocular irritation in rabbits when administered at concentrations up to 100%.
      Octyl Dodecanol (30% and 100%) was nonirritating to skin in one study using
      rabbits. In another study using multiple species, 100% Octyl Dodecanol (described
      as technical grade) caused severe skin irritation in rabbits, moderate irritation
      in guinea pigs and rats, and no irritation in swine. Stearic Acid was non- to
      moderately irritating in animal studies, and did not cause photosensitization. In
      studies using rabbits, undiluted Octyl Stearate caused slight, transient ocular
      irritation, and minimal skin irritation. Stearic Acid did not induce mitotic
      crossovers and aneuploidy in Saccharomyces cerevisiae, and was nonmutagenic in
      the Ames test. In a feeding study using mice, Stearic Acid was noncarcinogenic at
      doses up to 50 g/kg/day. Mice given subcutaneous injections of the acid had low
      incidences of carcinomas, sarcomas, and lymphomas. In clinical studies,
      concentrations of up to 100% Octyl Dodecanol were non- to mildly irritating,
      nonsensitizing, nonphototoxic, and nonphotosensitizing. Stearic Acid was
      nonirritating at concentrations up to 100%, and at concentrations up to 13% it
      was nonsensitizing and nonphotosensitizing. Octyl Stearate (7.6%) in formulation
      was nonirritating, nonsensitizing, and nonphotosensitizing. Based on skin
      permeation and penetration data, the Panel does not expect any significant amount
      of Octyldodecyl Stearoyl Stearate to be systemically available. There is no
      evidence of systemic toxicity associated with any of the related chemicals
      reviewed in previous safety assessments. None of the available toxicology or
      clinical data suggest a concern about adverse skin reactions to Octyldodecyl
      Stearoyl Stearate, or to any of the related chemicals. There is no evidence of
      ocular toxicity, except for a mild, transient ocular irritation associated with
      Octyldodecyl Stearoyl Stearate and the related chemicals. Overall, Octyldodecyl
      Stearoyl Stearate was considered safe as used in cosmetics.

PMID- 16422266
TI  - Final report of the safety assessment of Acacia catechu gum, Acacia concinna
      fruit extract, Acacia dealbata leaf extract, Acacia dealbata leaf wax, Acacia
      decurrens extract, Acacia farnesiana extract, Acacia farnesiana flower wax,
      Acacia farnesiana gum, Acacia senegal extract, Acacia senegal gum, and Acacia
      senegal gum extract.
AB  - These ingredients are derived from various species of the acacia plant. Only
      material derived from Acacia senegal are in current use according to industry
      data. The concentration at which these ingredients are reported to be used ranges
      from 9% in mascara to 0.0001% in tonics, dressings, and other hair-grooming aids.
      Gum arabic is a technical name for Acacia Senegal Gum. Gum arabic is comprised of
      various sugars and glucuronic acid residues in a long chain of galactosyl units
      with branched oligosaccharides. Gum arabic is generally recognized as safe as a
      direct food additive. Little information is available to characterize the
      extracts of other Acacia plant parts or material from other species. Acacia
      Concinna Fruit Extract was generally described as containing saponins, alkaloids,
      and malic acid with parabens and potassium sorbate added as preservatives.
      Cosmetic ingredient functions have been reported for Acacia Decurrens Extract
      (astringent; skin-conditioning agent--occlusive) and Acacia Farnesiana Extract
      (astringent), but not for the other Acacias included in this review. Toxicity
      data on gum arabic indicates little or no acute, short-term, or subchronic
      toxicity. Gum arabic is negative in several genotoxicity assays, is not a
      reproductive or developmental toxin, and is not carcinogenic when given
      intraperitoneally or orally. Clinical testing indicated some evidence of skin
      sensitization with gum arabic. The extensive safety test data on gum arabic
      supports the safety of Acacia Senegal Gum and Acacia Senegal Gum Extract, and it
      was concluded that these two ingredients are safe as used in cosmetic
      formulations. It was not possible, however, to relate the data on gum arabic to
      the crude Acacias and their extracts from species other than Acacia senegal.
      Therefore, the available data were considered insufficient to support the safety
      of Acacia Catechu Gum, Acacia Concinna Fruit Extract, Acacia Dealbata Leaf
      Extract, Acacia Dealbata Leaf Wax, Acacia Decurrens Extract, Acacia Farnesiana
      Extract, Acacia Farnesiana Flower Wax, Acacia Farnesiana Gum, and Acacia Senegal
      Extract in cosmetic products. The additional data needed to complete the safety
      assessment for these ingredients include (1) concentration of use; (2) identify
      the specific chemical constituents, and clarify the relationship between crude
      Acacias and their extracts and the Acacias and their extracts that are used as
      cosmetic ingredients; (3) data on contaminants, particularly relating to the
      presence of pesticide residues, and a determination of whether Acacia melanoxylon
      is used in cosmetics and whether acamelin (a quinone) and melacacidin (a flavin)
      are present in the Acacias that are being used; (4) skin sensitization study
      (i.e., dose response to be determined); (5) contact urticaria study at use
      concentration; and (6) ultraviolet (UV) absorption spectrum; if there is
      significant absorbance in the UVA or UVB range, then a photosensitization study
      may be needed. It was also noted that other data may be needed after
      clarification of the chemical constituents of the Acacia-derived ingredients.

PMID- 16422267
TI  - Barriers to quality end-of-life care in West Virginia ICU units: physicians' and
      nurses' prospectives.
AB  - Most deaths in West Virginia occur in hospitals and a high proportion take place
      in intensive care units (ICU). This study was undertaken to determine what West
      Virginia physicians and nurses treating patients in ICUs perceive to be the
      barriers to quality end-of-life care. A total of 626 physicians and nurses
      practicing in 28 hospitals completed surveys and the results showed that
      physicians and nurses agree the top three barriers are patient/family demands for
      all possible treatment; inadequate insurance coverage; and lack of health care
      professional education. The study indicated that the majority of physicians were
      satisfied with their end-of-life care skills. In addition, it showed that
      physicians referred an average of 10 patients to hospice in the preceding year
      and that they did not refer more patients because the patient or family did not
      accept that the patient was dying. Futher education of physicians, nurses and
      especially the public is needed to improve end-of-life care in West Virginia.

PMID- 16422268
TI  - The critical issue of quality child care.

PMID- 16422269
TI  - Prognostic indicators for stage II (Dukes' stage B) adenocarcinoma of the colon.
AB  - To determine the prognostic indicators that are associated with lower disease
      free survival (DFS) and overall survival (OS) in stage II colon cancer patients,
      the tumor registry records were reviewed for all patients diagnosed with stage II
      and III adenocarcinoma of the colon at Charleston Area Medical Center from 1986
      to 1994. The prognostic indicators of 174 stage II patients who had not undergone
      treatment were assessed for DFS and OS. The results demonstrated that the 5-year
      OS was reduced for those patients with the following prognostic indicators: male,
      obstruction at time of presentation, need for blood transfusion, and those who
      had < 7 LNR (lymph nodes removed). In addition, DFS and OS curves for stage II
      patients with < 7 LNR were not significantly different from survival curves for
      stage III patients. Treatment decisions are made based primarily on stage, and
      stage II patients are not routinely offered adjuvant therapy. Placing patients on
      a randomized clinical trial, until a standardized treatment is agreed upon, is
      one alternative. If patients are ineligible for, or refuse a clinical trial, then
      patients with poor prognostic indicators should be considered for adjuvant
      treatment.

PMID- 16422270
TI  - A 34-year-old man with Darier-White disease: a case report and review of the
      literature.
AB  - Darier-White disease is an uncommon genodermatosis that is commonly under
      recognized and is characteristically refractory to treatment. It is most
      frequently due to an autosomal dominant mutation in an intracellular calcium
      pump. It can be associated with severe cutaneous infections requiring
      hospitalization as well as neurologic and psychiatric comorbid disease. There are
      many treatment modalities described in the literature and systemic retinoids are
      the most effective. An increased clinical suspicion could possibly lead to a
      decreased delay in the diagnosis of this disease and an increased quality of life
      for these patients. We report a case of a man with Darier-White disease followed
      by a review of the current literature on the pathogenesis, clinical features,
      diagnosis, and treatment of this cutaneous malady.

PMID- 16422272
TI  - The healing arts: pushing the boundaries.

PMID- 16422271
TI  - A study of squamous cell carcinoma of the lip at West Virginia University
      Hospitals from 1980-2000.
AB  - The goal of this study was to review the patterns of relapse and outcome for
      patients with squamous cell carcinoma of the lip treated at West Virginia
      University Hospitals, and to assess the tumor factors that may influence the
      prognosis of patients. A total of 52 patients were identified in a retrospective
      review of all lip cancer patients referred to West Virginia University Hospitals
      between 1980 and 2000. Relevant data was extracted from the medical records of
      each patient, as well as information from the Cancer Registry. Most patients were
      men (86%) with T1N0 cancers (52%) of the lower lip. Less than 10% had nodal
      disease at diagnosis. Following treatment, 31% of patients relapsed, 7 at the
      primary site and 9 at regional lymph nodes. The relapse rate was 15% for T1
      lesions, whereas it increased to 44% for T2 lesions. The overall crude 5-year
      survival rate was 69%. These findings highlight an increased relapse rate and
      mortality for a subgroup of patients diagnosed with a more aggressive form of lip
      cancer. Treatment and follow up of these patients should accordingly be more
      aggressive.

PMID- 16422273
TI  - Pharmacotherapy for insomnia.

PMID- 16422274
TI  - The power of friendship: the Compeer Program at the University of Massachusetts
      Dartmouth.
AB  - Diminishing financial support for individuals with severe mental illnesses has
      required creative solutions to meet the needs of this population. Loneliness and
      stigma further hinder these individuals' efforts toward recovery. The Compeer
      program can provide friendship relationships, which can help to reduce loneliness
      and strengthen the effects of psychosocial interventions. University Compeer
      programs have proven successful in meeting the needs of both students and their
      Compeer friends.

PMID- 16422275
TI  - Long-acting injectable risperidone: an emerging tool in schizophrenia treatment.
AB  - Long-term treatment of patients with schizophrenia remains challenging.
      Functional and cognitive declines associated with schizophrenia compromise
      patients' ability to adhere to therapy. While medications can improve outcomes,
      partial adherence limits effectiveness and is associated with relapse and
      rehospitalization. Partial adherence has been shown to be high with both oral
      conventional and oral atypical antipsychotic agents. While long-acting
      conventional antipsychotic agents provide ensured medication delivery and reduce
      relapse rates, they carry a substantial risk of movement disorders. A new long
      acting formulation of the atypical agent risperidone has shown improved efficacy
      with decreased risk of adverse events. Its use, along with psychosocial
      approaches focused on adherence, may help, if initiated during inpatient
      treatment, by promoting adherence immediately postdischarge and improving long
      term treatment outcomes.

PMID- 16422276
TI  - Recovering from severe mental illness: mutual influences of self and illness.
AB  - A growing body of literature on the subjective experiences of people with severe
      mental illness (SMI) reveals the importance of the experience of self. The
      current study explored how the course of SMI is related to individuals'
      subjective experience of self. Bimonthly, comprehensive, semi-structured
      interviews with 43 people who had been discharged from psychiatric
      hospitalization were conducted over a 1-year period. Qualitative analysis of the
      data revealed mutual influences between the experience of self and illness over
      time. Conceptual and clinical implications of the relation between self and
      illness are discussed.

PMID- 16422277
TI  - The calcium connection to bone health across a woman's lifespan: a roundtable.
AB  - Adequate calcium throughout a woman's lifespan is a critical step to achieving
      and improving bone health. Unfortunately, there is no time across this continuum
      where the average intake is optimal. This paper reviews the output of a
      roundtable of scientific professionals who gathered to discuss approaches for
      turning high levels of awareness regarding the importance of adequate calcium
      intake into behaviors that actualize this recognition throughout the life of a
      woman. The critical time periods of pregnancy, lactation, perimenopause and
      menopause, in which adequate calcium intake is most important, are particularly
      highlighted. Recommended levels of calcium and vitamin D are reviewed with
      emphasis on diet and supplemental sources of these nutrients. Knowledge of the
      current shortfall in calcium intake across the life continuum coupled with health
      care professional education about the importance of compliance with
      recommendations will increase calcium awareness and utilization and improve bone
      health.

PMID- 16422278
TI  - National patterns of calcium use in osteoporosis in the United States.
AB  - OBJECTIVE: Although calcium intake is considered integral to appropriate
      management of osteoporosis, we hypothesized that the recent therapeutic dominance
      of bisphosphonates in osteoporosis treatment may have led calcium to be neglected
      as a component of effective management. STUDY DESIGN: Two national databases were
      used to assess the adequacy of calcium intake in patients with osteoporosis.
      Trends in reported supplemental calcium use among physician visits by patients
      with osteoporosis were assessed using nationally representative 1994-2004 IMS
      HEALTH National Disease and Therapeutic Index data. Quantity of calcium intake,
      from both supplements and food, among individuals with osteoporosis (n = 38 men
      and 376 women) was estimated using the 1999-2002 National Health and Nutrition
      Examination Survey (NHANES). RESULTS: Physician visits for osteoporosis in the
      United States increased 4.5-fold between 1994 (1.3 million visits) and 2004 (5.8
      million visits). During this time the proportion of osteoporosis visits in which
      bisphosphonates were prescribed increased from 14% to 81%, while reported calcium
      use fell from 43% to 23% of visits. Among osteoporosis patients in NHANES, 64%
      reported using calcium-containing supplements. Reported median calcium intake was
      433 (interquartile range: 295, 705) mg/d for calcium supplement nonusers and
      1,319 (845, 1,874) mg for calcium supplement users. Overall, only 40% of
      osteoporosis patients had calcium intake exceeding 1,200 mg/d. CONCLUSION: While
      osteoporosis is increasingly identified and treated with effective medications,
      calcium is being neglected as a component of osteoporosis management. Despite the
      fact that the efficacy of new osteoporosis medications depends on adequate
      calcium intake, reported calcium intake in osteoporosis patients is far below
      recommended levels.

PMID- 16422279
TI  - Elevated calcium requirements for women and unique approaches to improving
      calcium adherence.
AB  - Recent analyses from the Women's Health Initiative have shed new light on the
      importance of adequate calcium and vitamin D intake to women's bone health. This
      new information reveals the need for behavioral change in women's calcium and
      vitamin D intake. This is especially important considering that women, at certain
      points in their lives have calcium requirements that significantly increase, not
      only with menopause, but with pregnancy, post pregnancy and lactation. Despite
      the dissemination of this important information, women are still not complying
      with the calcium requirements. This paper will explore the reasons why women are
      not complying with the calcium requirements during their life course even though
      they are aware of the requirements.

PMID- 16422280
TI  - Calcium compliance: the clinician's role.
AB  - Clinician offices are the ideal location for patients to access reading material,
      videos and Web sites on bone health, effective prevention measures, treatments
      for osteoporosis and the importance of adequate calcium throughout the life
      cycle. For the clinician, the annual examination should be the time when
      evaluation and identification of patient risk factors for osteoporosis are done
      and the patient counseled on the need for adequate calcium, either through diet
      or supplement; vitamin D; and weight-bearing exercise. Women depend on their
      physicians for advice and counseling regarding both prescription and
      nonprescription interventions and therapies for bone health. The clinician's
      office should have a comprehensive sampling of educational materials that are of
      use to patients both for educating them about general preventive health practices
      as well as for giving them background information that will equip them to ask the
      physician health questions that directly pertain to them.

PMID- 16422281
TI  - Toward a better understanding of calcium intake: behavioral change perspectives.
AB  - This paper reviews what is currently known about the determinants of calcium
      intake. The paper focuses on findings from 3 studies conducted from 1994 to 2000
      to examine the determinants of calcium intake among women at midlife. These 3
      studies used the precaution adoption process model as a theoretical framework.
      Findings from other studies that have examined the determinants of calcium intake
      using different theoretical frameworks in different population groups are also
      presented. The findings reviewed suggest that there is a high level of awareness
      among women that consuming an inadequate amount of calcium increases their risk
      of developing osteoporosis but that this awareness is not being translated into
      long-lasting behavior change. Even when individuals are interested in increasing
      their calcium intake, perceived barriers often appear to prevent them from acting
      or lead to recidivism. Thus, in working with patients, clinicians should solicit
      patient concerns about trying to increase their calcium intake and barriers that
      the patient has experienced in the past or may anticipate in the future. In
      addition, this review notes a glaring lack of research concerning calcium intake
      among men and members of ethnic minorities and calls for future research focusing
      on more diverse populations.

PMID- 16422282
TI  - Prices and healthcare.

PMID- 16422283
TI  - Positive precepting for tomorrow.

PMID- 16422284
TI  - The issue that confronts us in private practice.

PMID- 16422285
TI  - The perfect world.

PMID- 16422286
TI  - Dentistry is for me!

PMID- 16422287
TI  - A continuing commitment.

PMID- 16422288
TI  - A vision of dentistry and medicine: a natural fit.

PMID- 16422289
TI  - Moving forward.

PMID- 16422290
TI  - Are we there yet?

PMID- 16422291
TI  - A united front.

PMID- 16422292
TI  - Discovering a whole new world.

PMID- 16422293
TI  - Afghanistan--revisited.

PMID- 16422294
TI  - Improve treatment acceptance by using patient payment plans.

PMID- 16422295
TI  - Oral and maxillofacial pathology case of the month. Molluscum contagiosum.

PMID- 16422296
TI  - Feasibility and prospects for a vaccine to prevent cryptococcosis.
AB  - Cryptococcosis is a relatively common fungal disease caused by Cryptococcus
      neoformans that has high morbidity and mortality. Numerous studies have
      established the feasibility of enhancing host immunity to C neoformans in naive
      immunocompetent animal models by vaccination. Several antigens have been
      identified that appear to be suitable vaccine candidates. Induced immune
      responses can mediate protection through both humoral and cellular immunity.
      Hence, a vaccine against cryptococcosis in humans is probably feasible but there
      are significant obstacles to vaccine development that range from uncertainties
      about the pathogenesis of infection to economic considerations.

PMID- 16422297
TI  - Random sequencing of Paracoccidioides brasiliensis genes.
AB  - Paracoccidioides brasiliensis genome has been reported as having a size of about
      30 Mb. By digestion of genomic DNA from strain IVICPb 73 (ATCC 32071), we have
      constructed a DNA library with an insert size average of 8 kb in Escherichia coli
      XL1 Blue. We have fully sequenced 7 clones comprising 51,022 bp which represent
      20 putative protein-coding sequences (seven of them, partial) and one tRNA. The
      20 coding sequences cover 46% of the total 51,022 bp with introns present in 10
      out of the 20 sequences. Database similarity analysis reveals the presence of
      genes conserved in other fungal species and higher organisms, including humans.

PMID- 16422298
TI  - Emmonsiosis of subterranean rodents (Bathyergidae, Spalacidae) in Africa and
      Israel.
AB  - The presence of adiaspores of the fungal genus Emmonsia was examined in the lungs
      of 85 mole rats representing 3 subterranean genera: blind mole rats (Spalax
      galili and S. golani) from Israel, Ansell's mole-rats (Cryptomys anselli) from
      Zambia, and silvery mole-rats (Heliophobius argenteocinereus) from Malawi and
      Zambia. Emmonsiosis was found in 28% of the blind mole rats, 100% of the Ansell's
      mole-rats, but in none of the silvery mole-rats. Infection in African mole-rats
      was caused by Emmonsia parva, and infection in Israeli blind mole rats was caused
      by E. parva and E. crescens. The study indicates that the perennial burrow system
      of the Ansell's mole-rat forms an appropriate microhabitat for the saprophytic
      growth of E. parva in Lusaka region, Zambia. We suggest that factors contributing
      to the striking difference in prevalence of emmonsiosis between the two African
      mole-rat genera (Cryptomys, Heliophobius) may be their differing burrow types,
      burrow longevity, and social lives.

PMID- 16422299
TI  - Vital growth factors of Malassezia species on modified CHROMagar Candida.
AB  - A comparison of several media, i.e., potato dextrose agar with olive oil (Oil
      PDA), modified Dixon agar (mDIX) and variations of Leeming and Notman agar (LNA)
      for the isolation and growth of Malassezia and Candida species was examined.
      Since LNA supported the highest growth of Malassezia species its key components,
      i.e., ox bile, glycerol monostearate, glycerol and Tween 60, were added to
      CHROMagar Candida. All 7 species of Malassezia grew well on this modified medium
      (LN-CHROM) after incubation for 4 days at 30 degrees C and development was equal
      to that observed on LNA. Colonies on LN-CHROM were smooth and from pink to dark
      purple in color. Furthermore, the use of LN-CHROM did not alter the colony
      characteristics of Candida species as compared to that found on CHROMagar
      Candida. The results of the present investigation indicate that the use of LN
      CHROM would make possible the simultaneous isolation and identification of
      Malassezia and Candida species.

PMID- 16422300
TI  - Coccidioidomycosis in hematopoietic stem cell transplant recipients.
AB  - Coccidioidomycosis is an endemic fungal infection of the desert southwestern
      United States that can cause devastating disseminated infection in
      immunocompromised persons. Clinical coccidioidomycosis, which is caused by
      Coccidioides species, has been well characterized in patients who have had solid
      organ transplants, but it has rarely been described in patients who have received
      a hematopoietic stem cell transplant (HSCT). We report the experience of 121
      consecutive HSCT recipients at a single tertiary care institution in an endemic
      area. One patient had fatal disseminated coccidioidomycosis after receiving an
      allogeneic transplant, and 2 patients had pulmonary infection before successful
      autologous HSCT; 1 of these 2 had a reactivation of coccidioidal infection after
      HSCT but was treated and survived. Coccidioidomycosis was not commonly identified
      in HSCT recipients, even in the endemic area. A prospective evaluation is
      required to address the optimal use of coccidioidal serologic tests, antifungal
      protocols, and secondary prophylaxis in these patients.

PMID- 16422301
TI  - Human albumin promotes germination, hyphal growth and antifungal resistance by
      Aspergillus fumigatus.
AB  - Invasive aspergillosis is one of the most common deep-seated fungal infections
      among patients with an impaired immune system. Albumin is a serum protein
      commonly administered to critical patients. Our objective was to evaluate the in
      vitro effect of human albumin upon germination and hyphal growth of Aspergillus
      species, especially the most pathogenic, Aspergillus fumigatus, as well as its
      influence on antifungal drug activity. Human albumin induced, at normal serum
      concentrations (2-4%), a significant promotion of conidial germination by A.
      fumigatus, but not by Aspergillus flavus and Aspergillus niger. However, mycelium
      growth following germination was enhanced in all Aspergillus species. Minimal
      inhibitory concentrations (MIC) of all strains tested to amphotericin B and
      itraconazole increased in the presence of physiological concentrations of human
      albumin. Voriconazole activity was not, however, significantly affected by the
      presence of the protein. Conidial germination represents a crucial initial step
      in the progression to invasive disease, involving metabolic pathways that may
      differ considerably among Aspergillus species. Our results support the concept
      that human albumin may promote a faster onset and enhanced dissemination of
      invasive aspergillosis.

PMID- 16422302
TI  - Hygromycin B-resistance phenotype acquired in Paracoccidioides brasiliensis via
      plasmid DNA integration.
AB  - Yeast cells of the human pathogenic fungus Paracoccidioides brasiliensis strain
      Pb01 were transformed to hygromycin B resistance using the plasmid pAN7.1.
      Transformation was achieved by electroporation, with intact or linearized plasmid
      DNA. The fungus was transformed using 200 mM manitol, 5 or 7 kV/cm field
      strength, 25 microF capacitance, 400 omega resistance, 5 microg plasmid DNA and
      10(7) yeast cells in 400 microl, and selected in BHI medium overlaid with 30
      microg/ml hygromycin B (hygB). Mitotic stability was assessed by growing
      transformants on non-selective BHI medium, followed by plating on hygromycin B
      (30 microg/ml). Transformants were analyzed by PCR and Southern blotting,
      confirming the hph gene integration into the transformants genome. A low level of
      stability of the integrated hph sequence in the transformant genomes was
      observed, probably because of the multinuclearity of P. brasiliensis yeast cells.

PMID- 16422303
TI  - Molecular detection of Paracoccidioides brasiliensis in soil.
AB  - The objective of the present study was to evaluate different techniques for the
      detection of Paracoccidioides brasiliensis in soil, e.g., culture, animal
      inoculation and specific DNA amplification by Nested PCR. We designed species
      specific inner primers derived from rDNA regions (ITS, 5.8S gene) and found their
      sensitivity to be higher than culture and animal inoculation. In addition, the
      sensitivity of these primers was higher than p27-gene primers developed for
      detection of P. brasiliensis in soil in a previous study. DNA from P.
      brasiliensis was detected in soil artificially seeded with the fungus (positive
      soil control) and from environmental samples collected in an armadillo burrow.

PMID- 16422304
TI  - Septic Candida krusei thrombophlebitis of inferior vena cava with persistent
      fungemia successfully treated by new antifungal agents.
AB  - Treatment of Candida krusei fungemia can be problematic. We describe a 44-year
      old critically ill, non-immunocompromised patient who had persistent Candida
      krusei fungemia complicated with septic thrombophlebitis of the inferior vena
      cava. Successful treatment was achieved by parenteral caspofungin followed by
      prolonged oral voriconazole. Persistent fungemia in the face of ongoing
      antifungal therapy and prompt removal of central line should alert physicians to
      the diagnosis of septic thrombophlebitis. Though combined therapy with
      amphotericin B and surgical intervention probably remains the treatment of
      choice, prolonged new antifungal agents, which have better efficacy, tolerability
      and bioavailability, may be a useful alternative where the central veins are
      relatively inaccessible or the patient is at high operative risk.

PMID- 16422305
TI  - Phenotypic identification of Candida albicans by growth on chocolate agar.
AB  - In this study, we describe a simple method for the identification of Candida
      albicans in clinical samples. A total of 383 clinical isolates of Candida species
      were streaked onto chocolate agar and incubated for 48 h at 37 degrees C in the
      presence of an atmosphere of 6% CO2. All 208 of the C. albicans isolates tested,
      developed an easy to identify filamentous colony morphology. Of 175 other Candida
      species tested, 172 (98.3%) were distinguishable from C. albicans by their smooth
      colony morphology. Three isolates (1.7%) exhibited weak filamentation after
      prolonged incubation. Although not a routine medium in medical mycology a
      significant advantage of using chocolate agar lies in its use in clinical
      bacteriology laboratories for the isolation of fastidious bacteria.
      Implementation of the proposed method is applicable across a range of specimen
      types, thus allowing the direct identification of C. albicans in clinical
      samples. This simple method may allow a quicker entry into directed treatment.

PMID- 16422306
TI  - Tobacco agar--used and reused.

PMID- 16422307
TI  - Monitoring event times in early phase clinical trials: some practical issues.
AB  - BACKGROUND: In many early phase clinical trials it is scientifically
      inappropriate or logistically infeasible to characterize patient outcome as a
      binary variable. In such settings, it often is more natural to construct early
      stopping rules based on time-to-event variables. This type of design may involve
      a variety of complications, however. PURPOSE: The purpose of this paper is to
      illustrate by example how one may deal with various complications that may arise
      when monitoring time-to-event outcomes in an early phase clinical trial. METHODS:
      We present a series of Bayesian designs for a phase II clinical trial in kidney
      cancer. Each design includes a procedure for monitoring the times to a severe
      adverse event, disease progression and death. The first design, which is the
      simplest, is based on the time to failure, defined as any of the three events,
      assuming exponentially distributed failure times with an inverse gamma prior on
      the mean. This design is compared by simulation to the CMAP design (Cheung and
      Thall, Biometrics, 2002; 58: 89-97). The model and monitoring procedure are then
      extended successively to accommodate several common practical complications, and
      we also study the method's robustness. RESULTS: Our simulations show that 1) one
      may apply the monitoring rule periodically, rather than continuously, without a
      substantive degradation of the design's reliability; 2) it is very important to
      account for interval censoring due to periodic evaluation of disease status; 3)
      it is important to account for the effect of disease progression on the
      subsequent death rate; 4) conducting a randomized trial presents little
      additional difficulty and provides unbiased comparisons; and 5) the exponential
      inverse gamma model is surprisingly robust in most cases. LIMITATIONS: The
      methods discussed here do not account for patient heterogeneity. This is an
      important but complex issue that may be dealt with by extending the models and
      methods given here to accommodate patient covariates and treatment-covariate
      interaction. CONCLUSIONS: Bayesian procedures for monitoring time-to-event
      outcomes offer a practical way to conduct a variety of early phase trials.
      Considerable care must be given, however, to modeling the important aspects of
      the trial at hand, and to calibrating the prior and the design parameters to
      ensure that the design will have good operating characteristics.

PMID- 16422308
TI  - Group sequential methods for cluster randomization trials with binary outcomes.
AB  - BACKGROUND: Cluster randomization trials in which intact social units are
      randomly assigned to different intervention groups have become very popular in
      recent years, particularly for the evaluation of innovations in the delivery of
      health care. An extensive literature dealing with the associated methodological
      challenges has also appeared. Although the monitoring of such trials using formal
      stopping rules is clearly indicated when the outcomes are irreversible and
      individual-level data are available sequentially, simple and reliable statistical
      methods that may be used for this purpose are currently not available. PURPOSE:
      To investigate the validity of standard group sequential methods when applied to
      cluster randomization trials having binary outcomes. METHODS: The large sample
      distributions for each of five test statistics computed from sequentially
      accumulated data are derived. A simulation study is performed to evaluate the
      finite sample properties of these statistics when applied to the interim analysis
      of cluster randomization trials. Data from the World Health Organization
      antenatal care trial are used to illustrate the methods. RESULTS: Each of the
      joint distributions is shown to be characterized by a covariance structure that
      asymptotically satisfies an independent increments structure, a foundation that
      simplifies group sequential methods. The simulation study reveals that four of
      the five test statistics evaluated provide satisfactory performance with as few
      as 10 clusters allocated to each of two interventions. LIMITATIONS: The
      applicability of our results to effect estimation following a group sequential
      cluster randomization trial is not investigated, although a theoretical
      foundation which may be used for this purpose is presented. CONCLUSIONS: Standard
      group sequential methods can be applied to cluster randomization trials when
      interim analyses are warranted.

PMID- 16422309
TI  - Nonignorable censoring in randomized clinical trials.
AB  - BACKGROUND: In a clinical trial, survival may be censored by the end of the
      study, especially for subjects who enter later in the enrollment period. If there
      is a trend toward better survival over time then longer survivors experience
      shorter censoring times (heavier censoring). In such a case, the censoring and
      survival times are correlated, and thus the censoring is nonignorable in the
      sense that standard survival models that assume independent censoring could yield
      incorrect inferences. We will demonstrate a graphical method for analyzing
      sensitivity of estimates of survival model parameters to small departures from
      nonignorable censoring. METHODS: We assume a parametric model of survival
      together with a scaled beta model for the censoring process that incorporates the
      dependence of censoring time on survival time. We assess sensitivity using an
      index of local sensitivity to nonignorability (Troxel et al.). High sensitivity
      indicates a large impact of nonignorable censoring on the parameter of interest
      and a need for additional modeling. RESULTS: A simulation study shows that the
      approach is valid for practical use. We apply our method to a clinical trial
      evaluating the survival benefit of a surgically implanted left ventricular assist
      device in subjects with end-stage heart failure. Sensitivity is somewhat larger
      in estimates of the mean survival in the device arm, where survival is better and
      the fraction censored is therefore larger. The degree of nonignorability required
      to substantially affect estimates is larger than seems plausible, however.
      CONCLUSIONS: Our results illustrate how one can apply sensitivity analysis to
      evaluate the reliability of survival parameter estimates in a clinical trial.

PMID- 16422310
TI  - Identifying methodologies in the assessment of treatment effects on the repeated
      occurrences of hot flashes in postmenopausal women.
AB  - BACKGROUND: Two methods that are commonly used in most clinical trials for
      evaluating the effect of treatment on hot flashes are frequency only and severity
      score methods. However, in these crude methods, composite recurrent hot flash
      data on a patient are reduced to a one-dimensional summary measure, an approach
      which may not be optimal. In addition, the duration of a hot flash event provides
      additional information, which is not accounted for in the two methods mentioned
      above. PURPOSE: We propose two new methods in the analysis of hot flash data in
      this paper. METHODS: The first method utilizes a generalization of the
      continuation ratio model to model the severity of a hot flash event. The model
      accounts for individual random effects and dependence of recurrent events within
      an individual. The other method that accounts for the duration of a hot flash
      event is a 3-Dimensional (3D) score method, which incorporates hot flash
      information on frequency, severity, and duration. RESULTS: Simulation studies
      were conducted to evaluate the properties of our proposed methods. The results
      indicate that our proposed generalized continuation ratio model has appreciably
      high power in detecting small treatment effects on severity compared with the two
      commonly used methods. The proposed 3D score, on the other hand, is sensitive in
      detecting treatment effects on both frequency and duration, but has low power in
      detecting treatment effects on severity alone. CONCLUSIONS: Our proposed
      generalized continuation ratio model approach provides a valuable and powerful
      alternative to the two commonly used methods in the analysis of treatment effects
      on hot flash severity. Our proposed 3D score method incorporates the additional
      information hot flash duration provides, and is another analysis option for the
      practitioners to employ.

PMID- 16422311
TI  - Non-linearity of Parkinson's disease progression: implications for sample size
      calculations in clinical trials.
AB  - BACKGROUND: Estimation of sample size for long-term studies of neuroprotection in
      Parkinson's disease requires information on expected clinical decline. Values may
      be obtained by analyzing existing long-term data sets or by prediction models of
      clinical decline applied to available data from shorter-term trials. The most
      commonly used measure to track clinical decline is the Unified Parkinson's
      Disease Rating Scale (UPDRS) but this measure is also affected by symptomatic
      therapy. Models can help better understand behavior of the UPDRS after initiation
      of symptomatic therapy when scores will improve and eventually start
      deteriorating again. PURPOSE: To understand how UPDRS scores progress after
      initiation of symptomatic therapy and how this progression impacts sample size
      calculations. METHODS: We developed a non-linear model of UPDRS after
      introduction of symptomatic therapy. The model is specified as a non-linear mixed
      effects model and is applied to three different data sets from clinical trials.
      The model is then used to produce estimates for the change in UPDRS and its
      associated variance for a period of up to five years of follow-up. The estimates
      produced by the model serve as the basis for sample-size calculations for
      different lengths of follow-up (one through five years) and for different values
      of clinically meaningful change in UPDRS. RESULTS: Despite differences in the
      short-term benefit of the dopaminergic drugs, after a period of approximately six
      months UPDRS scores progress linearly at an estimated rate of approximately three
      points a year. The sample size that is required for a clinical trial where the
      baseline coincides with initiation of symptomatic therapy is very large. On the
      other hand, if baseline is set at six months after initiation of symptomatic
      therapy then the sample size required decreases with length of follow-up.
      LIMITATIONS: Model specification and estimation is based on a set of simplifying
      assumptions regarding the progression of individual level UPDRS scores.
      CONCLUSIONS: Sample size calculations based on these estimates indicate a
      substantial reduction in sample size if patients are required to be on
      symptomatic treatment for a period of time before being randomized to a
      neuroprotective trial.

PMID- 16422312
TI  - A general formulation for a one-sided group sequential design.
AB  - BACKGROUND: A major contribution to the statistical literature on group
      sequential designs was provided by Pampallona and Tsiatis who developed closed
      form functions that can be used to iteratively calculate the boundary points of a
      family of popular group sequential designs. A related area of interest is the use
      of conditional probability calculations to make interim decisions in stochastic
      curtailment procedures. PURPOSE: The purpose of the paper is to develop group
      sequential designs based on conditional probabilities, to compare our results to
      the general closed form family of designs developed by Pampallona and Tsiatis,
      and to relate these to commonly used stochastic curtailment procedures. METHODS:
      The problem and its solution are formulated and derived mathematically. A
      graphical interpretation of the results provides the reader with an alternative
      mechanism to understand the results and their significance. RESULTS: One-sided
      group sequential design boundary points, as closed form functions, are derived
      from conditional probability statements. These conditional probability statements
      can be interpreted as the probability, at the final analysis, of reversing the
      conclusion reached at an interim state. Under mild constraints, these boundary
      points are identical to the Pampallona and Tsiatis boundary points. At any
      interim stage when a boundary point is attained or surpassed we suggest a
      graphical approach to examine the conditional probability of reversing the
      interim decision at the final stage versus a range of possible parameter values.
      For stochastic curtailment procedures, we recommend relaxing (increasing) the
      conditional probability levels to at least 0.50 so that early stopping is at
      least as likely as for the O'Brien-Fleming procedure. LIMITATIONS: The results
      are limited to one-sided group sequential designs. CONCLUSIONS: Conditional
      probabilities of reversing interim decisions provides a useful concept to develop
      group sequential designs and to evaluate stochastic curtailment procedures.

PMID- 16422313
TI  - Rationale and design of the Optimal Macro-Nutrient Intake Heart Trial to Prevent
      Heart Disease (OMNI-Heart).
AB  - BACKGROUND: The DASH (Dietary Approaches to Stop Hypertension) diet is a
      carbohydrate-rich, reduced-fat diet that lowers blood pressure (BP) and LDL
      cholesterol. Whether partial replacement of some carbohydrate (C) with either
      protein (P) or unsaturated fat (U) can further improve these and other
      cardiovascular (CVD) risk factors is unknown. METHODS: OmniHeart is a randomized,
      three-period, crossover feeding study designed to compare the effects on BP and
      blood lipids of a carbohydrate-rich diet (CARB, similar to the DASH diet) with a
      diet rich in protein (PROT, predominantly from nonmeat sources) and a diet rich
      in unsaturated fat (UNSAT, predominantly monounsaturated). Throughout feeding
      (run in and the three intervention periods), participants are provided with all
      of their meals that meet the nutrient profile of their assigned diet. Calorie
      intake is adjusted to maintain weight. The target sample size is 160 (50% African
      American). Participants are adults, aged 30 or older, with prehypertension or
      Stage 1 hypertension (systolic BP 120-159 or diastolic BP 80-99 mmHg). The
      primary outcome variables are systolic BP and LDL-cholesterol. Secondary outcomes
      are diastolic BP, HDL-cholesterol, and triglycerides. Other outcome variables are
      total cholesterol, apolipoproteins VLDL-apoB, VLDL-apoCIII, apolipoprotein B, non
      HDL cholesterol, and lipoprotein(a), and insulin resistance, as measured by
      Homeostasis Model Assessment (HOMA). CONCLUSIONS: OMNI-Heart should advance our
      fundamental knowledge of the effects of diet on both traditional and emerging
      risk factors, and, in the process, guide policy makers, health care providers and
      the general public on the relative benefits of carbohydrate, protein, and
      unsaturated fat as a means to reduce CVD risk.

PMID- 16422315
TI  - Optimization of anisotropically etched silicon surface-relief gratings for
      substrate-mode optical interconnects.
AB  - The optimum profiles of right-angle-face anisotropically etched silicon surface
      relief gratings illuminated at normal incidence for substrate-mode optical
      interconnects are determined for TE, TM, and random linear (RL) polarizations. A
      simulated annealing algorithm in conjunction with the rigorous coupled-wave
      analysis is used. The optimum diffraction efficiencies of the -1 forward
      diffracted order are 37.3%, 67.1%, and 51.2% for TE-, TM-, and RL-polarization
      optimized profiles, respectively. Also, the sensitivities to grating thickness,
      slant angle, and incident angle of the optimized profiles are presented.

PMID- 16422314
TI  - Clinical trials and epidemiological studies.

PMID- 16422316
TI  - Free-space-wave drop demultiplexing waveguide device fabricated by use of the
      interference exposure method.
AB  - Integration of free-space-wave add-drop multiplexers that consist of focusing
      grating couplers (FGCs) and distributed Bragg reflectors (DBRs) in thin-film
      waveguides have been investigated for construction of an intraboard wavelength
      division-multiplexing optical interconnection. Compact optics of a Lloyd mirror
      configuration and a contact-type mask aligner were combined as an interference
      exposure system for fabrication of DBRs of 300 microm coupling length. DBRs were
      integrated with FGCs on a thin-film waveguide on a glass substrate for two
      channel wavelength-drop demultiplexing from guided waves to free-space waves.
      Measured outcoupled wavelengths of two free-space waves from two pairs of a FGC
      and a DBR agreed with the design values of 845 and 849 nm.

PMID- 16422317
TI  - Synthetic diffractive elements for security applications realized on an enhanced
      integral dot-matrix system.
AB  - One of the important fields of application of synthetic diffractive structures is
      optical document security. Several methods of security enhancement of diffractive
      elements for security applications are presented, namely, high carrier-frequency
      cryptograms and noise-covered elements are introduced. Structures are designed
      with respect to the fabrication on special enhanced integral dot-matrix system.

PMID- 16422318
TI  - Development of a two-dimensional phase-grating mask for fabrication of an analog
      resist profile.
AB  - Fabrication of a thick analog profile with photoresist is a difficult task in
      photolithography. We demonstrate that a binary phase-grating photomask with an
      appropriate period and duty cycles is capable of manipulating the exposure
      illumination in an analog fashion and can be used for fabrication of the desired
      analog micro-optics profiles on the surface of a thick photoresist. By choosing
      the proper period and variation of duty cycle of the phase-grating mask, one can
      create the desired analog intensity of exposure illumination for an optical
      stepper. This allows the formation of a wide range of analog micro-optics
      profiles with an SPR 220-7 photoresist. The numerical convolution of the
      diffraction efficiency curve and resist exposure characteristics is used to
      predict the final resist profile and also to design the appropriate duty-cycle
      distribution for the binary phase grating. As a demonstration of this technology,
      we fabricated a variety of micro-optical elements, such as a positive lens, ring
      lens, prism, and vortex of approximately 100-200 microm diameter, by using a
      phase-grating mask fabricated in a poly(methyl methacrylate) electron-beam
      resist.

PMID- 16422319
TI  - Special features of Newton-type fringe formation in a diffraction interferometer.
AB  - An interferometer with a Fresnel zone plate located in the center of curvature of
      a concave mirror was studied. Attention was paid to the unique features of the
      interference field, which has a special point at which the path difference is
      equal to zero, thereby allowing for the observation of Newton-type fringes in
      white and quasi-monochromatic light. The conditions necessary for reducing the
      instrumental error to values less than lambda/20 were determined. Methods for
      suppressing noise and destructive interference patterns were also found.
      Metrological tests were carried out, and they proved the possibility of using
      this interferometer for industrial testing of spherical and parabolic mirrors.

PMID- 16422320
TI  - Zone-boundary optimization for direct laser writing of continuous-relief
      diffractive optical elements.
AB  - Enhancing the diffraction efficiency of continuous-relief diffractive optical
      elements fabricated by direct laser writing is discussed. A new method of zone
      boundary optimization is proposed to correct exposure data only in narrow areas
      along the boundaries of diffractive zones. The optimization decreases the loss of
      diffraction efficiency related to convolution of a desired phase profile with a
      writing-beam intensity distribution. A simplified stepped transition function
      that describes optimized exposure data near zone boundaries can be made universal
      for a wide range of zone periods. The approach permits a similar increase in the
      diffraction efficiency as an individual-pixel optimization but with fewer
      computation efforts. Computer simulations demonstrated that the zone-boundary
      optimization for a 6 microm period grating increases the efficiency by 7% and
      14.5% for 0.6 microm and 1.65 microm writing-spot diameters, respectively. The
      diffraction efficiency of as much as 65%-90% for 4-10 microm zone periods was
      obtained experimentally with this method.

PMID- 16422321
TI  - Cross-talk analysis in a telecentric adaptive free-space optical relay based on a
      spatial light modulator.
AB  - We present an analysis of the performance limit of an adaptive multichannel free
      space optical interconnect based on a spatial light modulator (SLM). The SLM
      function is to provide an active alignment of the signal beam in the detector
      plane. A thorough cross-talk analysis based on the diffractive properties of an
      ideal SLM in an isoplanatic optical system is shown. We analyze the performance
      in terms of the bit-error rate (BER) due to cross talk between different channels
      in the optical interconnect for different alignment states and for different
      phase-modulation schemes.

PMID- 16422322
TI  - Design of diffractive optical elements for the fractional Fourier transform
      domain: phase-space approach.
AB  - Phase-space optics is used to relate the problem of designing diffractive optical
      elements for any first-order optical system to the corresponding design problem
      in the Fraunhofer diffraction regime. This, in particular, provides a novel
      approach for the fractional Fourier transform domain. For fractional Fourier
      transforms of arbitrary order, the diffractive element is determined as the
      optimum design computed for a generic Fourier transform system, scaled and
      modulated with a parabolic lens function. The phase-space description also
      identifies critical system parameters that limit the performance and
      applicability of this method. Numerical simulations of paraxial wave propagation
      are used to validate the method.

PMID- 16422323
TI  - Replication of continuous-profiled micro-optical elements for silicon
      integration.
AB  - A novel scheme for the integration of diffractive optical elements onto silicon
      is presented. The processing is made in reverse order, meaning that the process
      of structuring the optical elements on the wafer precedes the silicon
      microstructuring. The first processing step on the wafer is the hot embossing of
      the optical microstructures into an amorphous fluorocarbon polymer spin coated on
      the wafer. The cured polymer forms a highly stable material with excellent
      optical properties. The remaining silicon processing is thus performed with the
      diffractive optical elements already in place. Two different diffractive
      structures were used in the development of the method-a (Fresnel) lens with a
      rather low f-number and a diffractive element producing a fan-out of a large
      number of paraxial beams.

PMID- 16422324
TI  - Efficient implementation of a spatial light modulator as a diffractive optical
      microlens array in a digital Shack-Hartmann wavefront sensor.
AB  - A traditional Shack-Hartmann wavefront sensor (SHWS) uses a physical microlens
      array to sample the incoming wavefront into a number of segments and to measure
      the phase profile over the cross section of a given light beam. We customized a
      digital SHWS by encoding a spatial light modulator (SLM) with a diffractive
      optical lens (DOL) pattern to function as a diffractive optical microlens array.
      This SHWS can offer great flexibility for various applications. Through fast
      Fourier-transform (FFT) analysis and experimental investigation, we studied three
      sampling methods to generate the digitized DOL pattern, and we compared the
      results. By analyzing the diffraction efficiency of the DOL and the
      microstructure of the SLM, we proposed three important strategies for the proper
      implementation of DOLs and DOL arrays with a SLM. Experiments demonstrated that
      these design rules were necessary and sufficient for generating an efficient DOL
      and DOL array with a SLM.

PMID- 16422325
TI  - Design and experimental test of diffractive superresolution elements.
AB  - By using previously established methods based on linear programming (MLP), we
      design and fabricate two types of diffractive superresolution element (DSE). The
      structure parameters and superresolution performances of the fabricated DSEs are
      tested. The test results agree well with the design results and are applicable to
      a writable or a read-only optical disk. Thus the application validity of the MLP
      is experimentally verified.

PMID- 16422326
TI  - Study of the injection molding of a polarizing beam splitter.
AB  - We describe the replication of a relief grating that behaves like a polarizing
      beam splitter by injection molding. Measurements of the grating master, nickel
      shim, and replica, performed by atomic force microscopy, allow establishing a
      limit for the injection molding technique (currently used in CD fabrication) to
      aspect ratios of approximately 0.15. Although this limit strongly reduces the
      diffraction efficiency of the elements as well as their polarizing properties,
      extinction ratios of approximately 10:1 were measured for the replicas in a large
      range of wavelengths.

PMID- 16422327
TI  - Design of adjustable superresolving filters based on birefringent crystals.
AB  - A two-mode adjustable superresolving filter based on a birefringent filter is
      proposed. This kind of filter has superresolution in two modes of adjustment. One
      is rotation of the binary pupil filter on the optical axis of the system and the
      other is the tilt of the filter away from the pupil plane on axis parallel or
      perpendicular to the optical axis of the crystal. The filters act as complex
      amplitude filters in the former mode, and as pure phase filters in the latter. By
      analyzing two superresolving parameters, we obtain the optimal design parameters
      that ensure a large field of view, a large superresolving range, and a high
      setting accuracy. This kind of filter can provide more flexibility in practical
      applications.

PMID- 16422328
TI  - Defect-free switchable phase grating.
AB  - Liquid-crystal-filled polymer structure devices offer a very low cost switchable
      spatial phase modulator. The phase profile set by the polymer structure may be
      varied or switched on/off with an applied field. Defects have been observed in
      some devices giving rise to spurious diffraction peaks. Computational modeling of
      the liquid-crystal director profile suggests that these defects might be
      suppressed if the dimensions of the liquid-crystal region are small. Experimental
      measurements confirm that this approach is effective in controlling the defects.
      This provides a route to fabrication of low-cost switchable complex diffractive
      devices.

PMID- 16422329
TI  - Topography characterization of a deep grating using near-field imaging.
AB  - Using near-field optical microscopy at the wavelength of 633 nm, we image light
      intensity distributions at several distances above an approximately 2-microm-deep
      and a 1-microm-period glass grating illuminated from below under the condition of
      total internal reflection. The intensity distributions are numerically modeled,
      and an inversion procedure based on a least-squares-fit optimization is employed
      to extract the grating geometry from the optical images.

PMID- 16422330
TI  - One-dimensional to two-dimensional channel formatting with micro-optics for
      wavelength division multiplexing networks.
AB  - We present a method of interfacing a conventional wavelength multiplexing and
      demultiplexing device with a two-dimensional (2-D) array of surface-active
      elements, such as micro-electromechanical system devices or photodetectors. We
      use diffractive optical elements to transform wavelength division multiplexed
      signals spread along a line into a 2-D array. We applied this technique to build
      a device that is compatible with an arrayed-waveguide grating. The theoretical
      insertion loss predicted by combining beam propagation and rigorous coupled-wave
      analysis is 2.75 dB. However, the experimental loss is 10 dB. The difference is
      due to the poor quality of the diffraction gratings. Nevertheless, the formatting
      operation was performed successfully.

PMID- 16422331
TI  - Transmittance analysis of three-dimensional photonic crystals by the effective
      medium theory.
AB  - A simple method for calculating the transmittance of three-dimensional photonic
      crystals is proposed. The crystals are divided into multilayer thin films, and
      each film is divided into rectangles with a minute width to calculate the
      effective permittivity of the film by the effective medium theory. Transmittance
      of the multilayer thin films is calculated with the matrix method. As the number
      of atomic layers increases, remarkable stop bands appear. When the refractive
      index of photonic atoms increases, the stop band shifts to a lower frequency, the
      band widens, and the number of bands increases. Polarization and incident angle
      dependences are also analyzed. The limit of application for this calculation
      method is also discussed.

PMID- 16422332
TI  - Interface engineered ultrashort period Cr-Ti multilayers as high reflectance
      mirrors and polarizers for soft x rays of lambda = 2.74 nm wavelength.
AB  - Cr-Ti multilayers with ultrashort periods of 1.39-2.04 nm have been grown for the
      first time as highly reflective, soft-x-ray multilayer, near-normal incidence
      mirrors for transition radiation and Cherenkov radiation x-ray sources based on
      the Ti-2p absorption edge at E = 452 eV (lambda = 2.74 nm). Hard, as well as
      soft, x-ay reflectivity and transmission electron microscopy were used to
      characterize the nanostructure of the mirrors. To achieve minimal accumulated
      roughness, improved interface flatness, and to avoid intermixing at the
      interfaces, each individual layer was engineered by use of a two-stage ion
      assistance process during magnetron sputter deposition: The first 0.3 nm of each
      Ti and Cr layer was grown without ion assistance, and the remaining 0.39-0.72 nm
      of the layers were grown with high ion-neutral flux ratios phi (phiTi = 3.3,
      phiCr = 2.2) and a low energy Eion (ETi = 23.7 and ECr = 21.2), ion assistance. A
      maximum soft-x-ray reflectivity of R = 2.1% at near-normal incidence
      (approximately 78.8 degrees) was achieved for a multilayer mirror containing 100
      bilayers with a modulation period of 1.379 nm and a layer thickness ratio of tau
      = 0.5. For a polarizing multilayer mirror with 150 bilayers designed for
      operation at the Brewster angle, 45 degrees, an extinction ratio, Rs/Rp, of 266
      was achieved with an absolute reflectivity of R = 4.3%.

PMID- 16422333
TI  - Extended focus diffractive optical element for Gaussian laser beams.
AB  - The depth of focus of the Gaussian beam is extended by introducing a wavefront
      phase correction with properly designed diffractive optical elements. Results of
      the computer simulations show that, compared with other methods, the presented
      method demonstrates a reduced focal spot size and low sidelobes in a focal
      domain, within a considerable range of defocusing distances. Experimental results
      for the visible range diffractive optical element with a focus of 40 mm and a
      depth of focus that extends to 1 mm agree with the theory.

PMID- 16422334
TI  - Influence of temperature on the sensitivity and signal-to-noise ratio of a fiber
      optic surface-plasmon resonance sensor.
AB  - We have theoretically analyzed the influence of temperature on the performance of
      a fiber-optic sensor based on surface-plasmon resonance (SPR). The performance of
      the sensor has been evaluated in terms of its sensitivity and signal-to-noise
      ratio (SNR). The theoretical model for temperature dependence includes the thermo
      optic effect in the fiber core and sensing layer, and phonon-electron scattering
      along with electron-electron scattering in the metal layer. The effect of
      temperature on the SNR and the sensitivity of the sensor with two different
      metals has been compared. The same comparison is carried out for the sensing
      layers with positive and negative thermo-optic coefficients. The theoretical
      model has been analyzed for both the nonremote and remote sensing cases. This
      detailed analysis of temperature-dependent SNR and sensitivity leads to achieving
      the best possible performance from a fiber-optic SPR sensor against the
      temperature variation.

PMID- 16422335
TI  - Efficient laser polishing of silica micro-optic components.
AB  - We report a study of the basic characteristics of laser polishing of fused silica
      with a protocol that is particularly suitable for surface smoothing of micro
      optic elements fabricated by a laser ablation process. We describe a new, to our
      knowledge, approach based on scanning a highly controlled small size laser beam
      and melting areas of tens to hundreds of micrometers of glass using a computer
      controlled raster scan process, which does not require beam shaping, substrate
      preheating, or special atmospheres. Special test samples of silica substrates
      with prescribed spatial frequency content were polished using a range of
      irradiation conditions with the beam from a well-controlled CO2 laser operating
      at a wavelength of 10.59 microm. An analysis is presented of the laser-generated
      reduction in surface roughness in terms of measurements of the spatial frequency
      characteristics, and the results are compared with the predictions of a simple
      model of surface-tension-driven mass flow within the laser-melted layer. This
      technique is shown to be capable of smoothing silica surfaces with approximately
      1 microm scale roughness down to levels < 1 nm with no net effect on the as
      machined net surface shape, at realistic production rates without a preheating
      stage, and with noncritical residual stresses.

PMID- 16422336
TI  - Highly reflecting aluminum-protected optical coatings for the vacuum-ultraviolet
      spectral range.
AB  - We discuss the approaches to preserve the high-reflectance aluminum mirror for
      the vacuum-ultraviolet spectral region. Single fluoride and oxide layers, a
      homogeneous multilayer, and hybrid multilayer solutions are put forward. Single
      fluoride and oxide materials have achieved reflectance above 90% at 193 nm.
      Multilayer capping can provide reflectance of 93.4% at 193 nm, and a hybrid
      multilayer of fluoride and oxide can achieve reflectance above 90% to 160 nm.

PMID- 16422337
TI  - Rugate filters fabricated by a radio frequency magnetron sputtering system by use
      of an optical in situ monitoring technique.
AB  - We propose, for the first time to our knowledge, a new feedback fabrication
      technique for rugate filters with sinusoidal refractive index distribution. The
      technique uses an in situ optical monitoring system, in contrast to conventional
      techniques for rugate filters that are based on time control, which is generally
      unsuitable for accurate fabrication of a continuous index distribution. We
      employed a-SiOx:H thin film as the material for the rugate filters because its
      refractive index can be successively controlled. Using the proposed technique and
      material, we fabricated near-infrared rugate minus filters having multiple and
      continuous refractive index distributions. The experimental and calculated
      spectra were well correlated as a result of applying the proposed feedback
      fabrication technique.

PMID- 16422338
TI  - Free-space optical communication through a forest canopy.
AB  - We model the effects of the leaves of mature broadleaf (deciduous) trees on air
      to-ground free-space optical communication systems operating through the leaf
      canopy. The concept of leaf area index (LAI) is reviewed and related to a
      probabilistic model of foliage consisting of obscuring leaves randomly
      distributed throughout a treetop layer. Individual leaves are opaque. The
      expected fractional unobscured area statistic is derived as well as the variance
      around the expected value. Monte Carlo simulation results confirm the predictions
      of this probabilistic model. To verify the predictions of the statistical model
      experimentally, a passive optical technique has been used to make measurements of
      observed sky illumination in a mature broadleaf environment. The results of the
      measurements, as a function of zenith angle, provide strong evidence for the
      applicability of the model, and a single parameter fit to the data reinforces a
      natural connection to LAI. Specific simulations of signal-to-noise ratio
      degradation as a function of zenith angle in a specific ground-to-unmanned aerial
      vehicle communication situation have demonstrated the effect of obscuration on
      performance.

PMID- 16422339
TI  - Principal component-based radiative transfer model for hyperspectral sensors:
      theoretical concept.
AB  - Modern infrared satellite sensors such as the Atmospheric Infrared Sounder
      (AIRS), the Cross-Track Infrared Sounder (CrIS), the Tropospheric Emission
      Spectrometer (TES), the Geosynchronous Imaging Fourier Transform Spectrometer
      (GIFTS), and the Infrared Atmospheric Sounding Interferometer (IASI) are capable
      of providing high spatial and spectral resolution infrared spectra. To fully
      exploit the vast amount of spectral information from these instruments, superfast
      radiative transfer models are needed. We present a novel radiative transfer model
      based on principal component analysis. Instead of predicting channel radiance or
      transmittance spectra directly, the principal component-based radiative transfer
      model (PCRTM) predicts the principal component (PC) scores of these quantities.
      This prediction ability leads to significant savings in computational time. The
      parameterization of the PCRTM model is derived from the properties of PC scores
      and instrument line-shape functions. The PCRTM is accurate and flexible. Because
      of its high speed and compressed spectral information format, it has great
      potential for superfast one-dimensional physical retrieval and for numerical
      weather prediction large volume radiance data assimilation applications. The
      model has been successfully developed for the NAST-I and AIRS instruments. The
      PCRTM model performs monochromatic radiative transfer calculations and is able to
      include multiple scattering calculations to account for clouds and aerosols.

PMID- 16422341
TI  - [Research in sciences of education. State of the art and points of view].

PMID- 16422342
TI  - [Multidisciplinary teams and method. Review of social work and nursing science
      research].

PMID- 16422343
TI  - [Reflection on the uses of the group interview].

PMID- 16422344
TI  - [The management of nutritional care in hospitals: comparative study Brazil
      France].
AB  - This study had as its proposal a comparative analysis, with the support of
      anthropotechnology, the management of nutritional care in hospital food and
      nutrition services both in Brazil and France. Data was obtained from documents,
      designed interviews and direct observation. The results with respect to France
      show that the characteristics observed offer conditions which are more favourable
      for dieticians. In Brazil, the low investment in health and education is even
      more challenging to dieticians. The recommendations to qualify the management of
      nutritional care were formulated in relation to the following aspects: the
      technology of management of nutritional care, strategies of interaction and
      organisation between clinical-nutritional attendance and the production of meals
      and background of dieticians.

PMID- 16422345
TI  - [Reflection upon returning from the Institute of Nursing Care Training: a space
      for dialogue in the development of the professional experience].
AB  - We were interested in the training practices undertaken by the trainers at the
      IFSI. And if there is a lot of research in this field, it is through the analysis
      of working situations, and more particularly in the field of professional
      education, that our research was carried out We observed how trainers proceed at
      the sessions when they come back from their training period, most often called
      "exploitation of training period". We tried to understand how they lead the
      reflective analysis, from the expression of the experience of the students in
      professional situations. We more particularly analysed how, from an object
      presented by a student, they act, contribute to progress, to the advance that
      will lead to the development of experience and therefore to the expansion of the
      students' capacity to act in working situations. We identified some particularly
      key elements. We used the concept of schema for the analysis, and our proposals
      also enable to expand the capacity of action of the trainers in the field of
      health.

PMID- 16422346
TI  - [Motivation: perspectives in education].

PMID- 16422347
TI  - Thermal stress and the physiological response to environmental toxicants.
AB  - Most toxicological and pharmacological studies are performed in laboratory
      animals maintained under comfortable environmental conditions. Yet, the exposure
      to environmental toxicants as well as many drugs can occur under stressful
      environmental conditions during rest or while exercising. The intake and
      biological efficacy of many toxicants is exacerbated by exposure to heat stress,
      which can occur in several ways. The increase in pulmonary ventilation during
      exposure to hot environments results in an increase in the uptake of airborne
      toxicants. Furthermore, the transcutaneous absorption of pesticides on the skin
      as well as drugs delivered by skin patches is increased during heat stress
      because of the combined elevation in skin blood flow coupled with moist skin from
      sweat. The thermoregulatory response to toxicant exposure, such as hypothermia in
      relatively small rodents and fever in humans, also modulates the physiological
      response to most chemical agents. This paper endeavors to review the issue of
      environmental heat stress and exercise and how they influence thermoregulatory
      and related pathophysiological responses to environmental toxicants, as well as
      exposure to drugs.

PMID- 16422348
TI  - Air pollution epidemiologic studies in South Africa--need for freshening up.
AB  - The results of epidemiologic studies obtained in developed countries cannot be
      extrapolated with complete confidence to developing countries. The objectives of
      this review were to examine the evidence from local studies for associations
      between air pollution and adverse health along with a critical review for
      methodologic limitations. The literature search strategy and selection criteria
      involved a MEDLINE search up to June 2005. Of 267 journal articles found, 14
      focused on air pollution epidemiology (excluding active smoking and internal dose
      as a proxy for health outcomes). Two studies were also located by word of mouth
      or through the references from the selected studies. The local studies provide
      some evidence of an association with a range of serious and common health
      problems. No study established an exposure-response curve for the criteria
      pollutants carbon monoxide, sulfur dioxide, nitrogen oxides, lead, and ozone.
      Therefore, using the results of such studies in risk-assessment is impossible.
      The studies were fraught with systematic and random errors, which limit their
      validity and precision. We recommend conducting a quantitative intervention study
      with an analytical study design in all major cities in the countries where
      residents are still using dirty fuels for cooking, lighting, and space heating.
      Future studies must involve national and international multidisciplinary
      stakeholders and must be planned well in advance.

PMID- 16422349
TI  - Environmentally and occupationally acquired diseases in adolescents and
      adulthood: control of diphtheria, tetanus, pertussis, and poliomyelitis through
      regular booster vaccinations--a European perspective.
AB  - Despite the success of childhood vaccination in industrialized countries,
      diphtheria, tetanus, pertussis (whooping cough), and poliomyelitis (polio) still
      affect adults and adolescents whose immunity has waned. The resurgence in the
      1990s of diphtheria in the area of the former Soviet Union and its subsequent
      control with immunization campaigns, demonstrates the value of continued adult
      vaccination. Tetanus cannot be eradicated from the soil reservoir, necessitating
      routine primary vaccination and regular booster doses to maintain protective
      immunity. Although Europe has been certified endogenous polio-free since June
      2002, polio imported from endemic areas continues to pose a serious threat for
      vulnerable populations. Booster polio vaccination is required in adolescence and
      adulthood. Pertussis among adults and adolescents is underestimated, representing
      a considerable health burden. The consequences can be more serious as this pool
      of susceptible adolescents and adults is a major source of pertussis transmission
      to newborns not yet protected by vaccination. The now available acellular
      pertussis-based combination vaccine covering diphtheria, tetanus, polio, and
      pertussis, suitable for adults and adolescents, provides the ideal tool for
      implementing booster immunization programs. Strong recommendations for adolescent
      and adult boosters are needed to overcome the continued threat of these diseases.

PMID- 16422350
TI  - [Coming technical advances in radiation oncology].
AB  - PURPOSE: To review the current limits on the efficacy of radiotherapy (RT) due to
      technical factors and to assess the potential for major improvements in
      technology. METHODS AND MATERIALS: The method of this review was to assess the
      efficacy of current RT in general terms; strategies for improving RT; historical
      record of technological advances; rationale for further reductions of treatment
      volume; and importance of defining and excluding nontarget tissues from the
      target volume. The basis for the interest in proton beam RT is developed, and the
      relative dose distributions of intensity-modulated radiotherapy (IMRT) and
      intensity-modulated proton RT (IMPT) are discussed. The discovery of the proton
      and the first proposal that protons be used in RT is described. This is followed
      by a brief mention of the clinical outcome studies of proton RT. Likely technical
      advances to be integrated into advanced proton RT are considered, specifically,
      four-dimensional treatment planning and delivery. Finally, the increment in cost
      of some of these developments is presented. RESULTS: For definitive RT, dose
      limits are set by the tolerance of normal tissues/structures adjacent or near to
      the target. Using imaging fusion of CT, MRI, positron emission tomography,
      magnetic resonance spectroscopic imaging, and other studies will result in
      improved definition of the target margins. Proton beams are likely to replace
      photon beams because of their physical characteristics. Namely, for each beam
      path, the dose deep to the target is zero, across the target it is uniform, and
      proximal to the target it is less. Proton therapy can use as many beams, beam
      angles, noncoplanar, and dynamic, as well as static, intensity modulation, as can
      photon plans. The ability for much greater accuracy in defining the target
      position in space and then maintaining the target in a constant position in the
      radiation beam despite target movement between and during dose fractions will be
      possible. The cost of proton RT will be modestly higher than comparable high
      technology photon therapy. CONCLUSION: The technology of RT is clearly
      experiencing intense and rapid technical developments as pertains to treatment
      planning and dose delivery. It is predicted that radical dose RT will move to
      proton beam technology and that the treatment will be four dimensional (the
      fourth dimension is time). The impact will be higher tumor control probability
      and reduced frequency and severity of treatment-related morbidity.

PMID- 16422351
TI  - [Experimental determination of the virtual source point of high-energy electron
      beams for clinical application].
AB  - In radiation therapy, electron beams are applied in many cases without the aid of
      treatment planning systems. When the geometrical conditions differ from the
      measurement conditions, the position of the virtual electron source must be known
      in order to convert the dosimetric data. According to the literature, there are
      multiple procedures for measuring the position of the virtual electron source,
      however these partially result in considerably different values. Therefore, the
      intended purpose of the virtual electron source must be clarifiedfirst, e.g.
      whether the correction of the field size or the calculation of the output in
      relationship to the focus-surface distance. Additionally, the scope of
      application must be clearly defined because the determined value, even for the
      same measuring method, is strongly dependent on the measurement range used for
      the evaluation. We investigated all common procedures and developed a new and
      very time-saving method. The method is presented in this paper, and the results
      and their impact on the application of electron beams under non-standard
      conditions are demonstrated and discussed.

PMID- 16422352
TI  - Comparison of the ESTRO formalism for monitor unit calculation with a Clarkson
      based algorithm of a treatment planning system and a traditional "full-scatter"
      methodology.
AB  - The ESTRO formalism for monitor unit (MU) calculations was evaluated and
      implemented to replace a previous methodology based on dosimetric data measured
      in a full-scatter phantom. This traditional method relies on data normalised at
      the depth of dose maximum (Zm), as well as on the utilisation of the BJR 25 table
      for the conversion of rectangular fields into equivalent square fields. The
      treatment planning system (TPS) was subsequently updated to reflect the new beam
      data normalised at a depth ZR of 10 cm. Comparisons were then carried out between
      the ESTRO formalism, the Clarkson-based dose calculation algorithm on the TPS
      (with beam data normalised at Zm and ZR), and the traditional "full-scatter"
      methodology. All methodologies, except for the "full-scatter" methodology,
      separated head-scatter from phantom-scatter effects and none of the
      methodologies; except for the ESTRO formalism, utilised wedge depth dose
      information for calculations. The accuracy of MU calculations was verified
      against measurements in a homogeneous phantom for square and rectangular open and
      wedged fields, as well as blocked open and wedged fields, at 5, 10, and 20 cm
      depths, under fixed SSD and isocentric geometries for 6 and 10 MV. Overall, the
      ESTRO Formalism showed the most accurate performance, with the root mean square
      (RMS) error with respect to measurements remaining below 1% even for the most
      complex beam set-ups investigated. The RMS error for the TPS deteriorated with
      the introduction of a wedge, with a worse RMS error for the beam data normalised
      at Zm (4% at 6 MV and 1.6% at 10 MV) than at ZR (1.-9% at 6 MV and 1.1% at 10
      MV). The further addition of blocking had only a marginal impact on the accuracy
      of this methodology. The "full-scatter" methodology showed a loss in accuracy for
      calculations involving either wedges or blocking, and performed worst for blocked
      wedged fields (RMS errors of 7.1% at 6 MV and 5% at 10 MV). The origins of these
      discrepancies were quantified and the shortcomings of these MU calculation
      methodologies are discussed in the paper.

PMID- 16422353
TI  - [Segmentation of the white matter in the brain based on MR-DTI fiber directions].
AB  - MR diffusion tensor imaging (DTI) allows the visualization of location and course
      of brain fiber bundles. To obtain these results, however, special evaluation
      techniques are necessary in addition to image acquisition and reconstruction.
      These include first the calculation of a preferential diffusional direction of
      water molecules in each voxel and then the tracking of brain fibers or
      segmentation of regions with similar fiber directions. In both cases, the
      procedures available thus far require the interactive definition of seed points.
      In this paper, we propose a method to segment voxel groups of connected data
      points without the need of setting seed points. This method is based first on the
      identification of all voxels of a brain volume with a sufficiently unique
      preferential diffusional direction and with interconnection. For each selected
      voxel, neighboring voxels are then identified that have a small deviation from
      the chosen preferential direction and can therefore be grouped with this point.
      Finally, the largest partial volumes determined in this way are marked and color
      coded to present them as three-dimensional structures. The present method
      resulting in a largely automatic subdivision of the white matter in the brain in
      a number of bilateral partial volumes.

PMID- 16422354
TI  - [Numerical simulations of pulsating flow in intracranial blood vessels with
      aneurysms using Lattice Boltzmann methods].
AB  - A major prerequisite for successful planning and control of the medical treatment
      of blood vessels with stenoses or aneurysms is the detailed knowledge of the
      individual situation in the damaged vessels. Modern tomography methods provide
      good spatial resolution, so that vessel walls as well as prostheses can be easily
      and rapidly identified. However, the mechanical loads of the walls remain largely
      unknown. In the past few years, tomography data have been used for spatial and
      temporal simulations of the blood flow in such vessels and to predict the
      mechanical loads of the vessel walls. The methodologies used so far, however,
      involve elaborate grid generation and simulation steps, most often relying on
      commercial software suited for engineering projects. These require specific
      knowledge and experience in mechanics and numerical simulation, and are therefore
      inappropriate for clinical applications. It is now shown, by example of an
      intracranial aneurysm, that employing a Lattice Boltzmann method for the flow
      simulation allows to avoid all mentioned drawbacks and to simulate blood flows in
      a fast and simple way that is also appropriate for clinical use. The practical
      relevance of such simulations will be enhanced by a better understanding of the
      correlations between pathology and specific mechanical loads. The paper discusses
      also some aspects of fluid mechanics that are relevant for the study of
      aneurysms.

PMID- 16422355
TI  - Recognition of malignant processes with neural nets from ESR spectra of serum
      albumin.
AB  - Cancer diseases are the focus of intense research due to their frequent
      occurrence. It is known from the literature that serum proteins are changed in
      the case of malignant processes. Changes of albumin conformation, transport
      efficiency, and binding characteristics can be determined by electron spin
      resonance spectroscopy (ESR). The present study analysed the binding/dissociation
      function of albumin with an ESR method using 16-doxyl stearate spin probe as
      reporter molecule and ethanol as modifier of hydrophobic interactions. Native and
      frozen plasma of healthy donors (608 samples), patients with malignant diseases
      (423 samples), and patients with benign conditions (221 samples) were analysed.
      The global specificity was 91% and the sensitivity 96%. In look-back samples of
      27 donors, a malignant process could be detected up to 30 months before clinical
      diagnosis. To recognise different entities of malignant diseases from the ESR
      spectra, Artificial neural networks were implemented. For 48 female donors with
      breast cancer, the recognition specificity was 85%. Other carcinoma entities (22
      colon, 18 prostate, 12 stomach) were recognised with specificities between 75%
      and 84%. Should these specificity values be reproduced in larger studies, the
      described method could be used as a new specific tumour marker for the early
      detection of malignant processes. Since transmission of cancer via blood
      transfusion cannot be excluded as yet, the described ESR method could also be
      used as a quality test for plasma products.

PMID- 16422356
TI  - [A dynamic heart phantom for quality control in functional nuclear cardiac
      imaging].
AB  - A dynamic heart phantom for the quality control of tomographic systems used in
      nuclear cardiology imaging was developed, built, and tested. The heart phantom
      anatomically simulates the left ventricle of the heart. The variable parameters
      are represented by the volume of the left ventricle, the temporal course of the
      filling event, and the frequency of the filling of the left ventricle. These
      parameters can reliably simulate the wall motion, wall thickening, ejection
      fraction, and stroke volume of the left ventricle.

PMID- 16422357
TI  - [A quantitative study of MRI-based treatment planning for the percutaneous
      radiation therapy of brain tumors].
AB  - This study examined to which extent treatment plans for brain tumors can be
      constructed with a commercial treatment planning system (TPS) based on MRI data
      only. CadPlan 6.4.7 was used as TPS. In particular, differences between MRT-based
      and conventional CT-based plans were examined systematically. The quantification
      of the retrospective evaluation was carried out by the point-wise dose difference
      and the gamma-distribution. In this study the gamma-distribution did not appear
      advantageous over the dose difference for the tolerance range (point-wise dose
      difference < 3%, distance criterion LLL 5 mm). The calculated dose distribution
      showed large differences (up to 103%) at the boundary of the treatment fields, in
      the regions of the head contour, and in areas with air inclusions and significant
      bone structures. The inner parts of the fields, and therefore the actual target
      volume, revealed only small deviations in the range of-2% in the homogeneous
      distribution.

PMID- 16422358
TI  - [Resolution and sensitivity of a two-dimensional ionisation chamber array (PTW
      type 10024)].
AB  - The two-dimensional verification of intensity-modulated radiation plans is one of
      the major requirements for the safe application of this technique. The present
      study examines the resolution and sensitivity of a two-dimensional ionisation
      chamber array (PTW2D-Array, type 10024), which can be used for plan verification
      instead of films. According to the Shannon-Nyquist theorem, the resolution of the
      2D-Array is sufficient for dose distributions with a minimal field size of 2 cm x
      2 cm. The minimal field size can be reduced to 1 cm x 1 cm by shifting the array
      5 mm in the direction of the MLC movement and by repeating the measurements. The
      high sensitivity against a monitor decalibration for a single field of a sequence
      is demonstrated on the basis of an individual case. The minimal threshold for MLC
      misalignment detected by a chamber of the array is less than 1 mm. Therefore, the
      resolution capabilities of the 2D-Array are sufficient for most intensity
      modulated radiation therapy (IMRT)fields.

PMID- 16422359
TI  - [Transrectal ultrasound in the diagnosis of prostate cancer].
AB  - Transrectal ultrasound is an important tool in detection and management of
      prostate cancer. Its role is to identify and characterize focal lesions before
      capsular invasion and metastases and to guide biopsy of the prostate. In this
      paper, we present a overview of the state of trans-rectal ultrasound imaging in
      prostate cancer.

PMID- 16422360
TI  - [Coelioscopy in gynecologic emergencies. About 239 cases].
AB  - OBJECTIVE: The goal of this study was to determine the efficiency of lapaorscopy
      as method of diagnosis and treatment of gynecologic emergencie. METHODS: A
      laparoscopy was performed in two hundred and thirty-nine patients who presented
      in emergency with signs like acute pelvic pain, uterine bleeding or fever.
      Diagnoses and treatments are presented in a retrospective study. RESULTS: The
      median patient age was 30.4 years and median parity was 14 sonography was
      performed in all patients and bHCG rate was positive in 101 patients. The most
      suspected diagnosis was ectopic pregnancy (42%) followed by complicated cysts
      (30%) and ligh genital infections (27%) At laparoscopy 92 cases of ectopic
      pregnancy, 66 cysts complicated or not and 47 high genital infections were found.
      Laparoscopy didn't show any evident pathology in 6.6% of patients. We didn't note
      any anesthesial or surgical complication. CONCLUSION: Laparoscopy for gynecologic
      emergencies can be satisfactorily performed in the majority of patients,
      regardingly to low fiability of usual diagnostic methods. II is useful for
      diagnosis and treatment. The rate of it's overall complications is relatively
      low.

PMID- 16422361
TI  - [Sedative practice in intensive care units results of a Maghrebian survey].
AB  - OBJECTIVES: sedation is central to the management of intensive care patients. The
      aim of this study was to establish the current sedation practice in Maghrebian
      intensive care units (ICUs). The use of sedation policies with or without a
      written protocol, the use of scoring systems, the influence of costs on drug
      choice, the most common drugs for sedation and the use of neuromuscular blocking
      agents. METHODS: a self-administered questionnaire composed of 20 items was sent
      to 138 intensivists in the Maghreb working in 25 teaching hospitals and 16
      private clinics. RESULTS: 50 of 138 questionnaires were returned (response rate =
      36.2%). Midazolam and Fentanyl were the main sedative agents used (respectively
      98% and 87%) less than 14% of the ICUs used the Propofol mainly in the first 48
      hours. A sedation policy was adopted in 63.6% with a written protocol in 20% of
      cases. Sedation scoring systems were noted in 14.3% of cases (RAMSAY scale in
      100%). Economic aspect was important for 64.6% of ICUs. DISCUSSION: sedation may
      seem secondary in the initial management of intensive care patients, only 63% of
      our respondents had a sedation policy and 20% a written protocol though its use
      is thought to improve outcome and reduce costs. Economic aspect was important for
      the choice of the drug to use (64%), this may explain the preferential use of
      Midazolam 98% in association with an analgesic (Fentanyl: 85%) while Propofol is
      used only in 14% though pharmacoeconomic studies may be in fact in favor of the
      latter. Neuromuscular blocking agents are less frequently used (16%) mainly
      because of the risk of complications.

PMID- 16422362
TI  - [Cryoglobulinemia in chronic hepatitis C virus infection. About 76 cases].
AB  - Cryolobulines are immunoglobulins that persist in the serum, precipitate with
      cold temperature and resolubilize when rewarmed. There are 3 types of
      cryoglobulinemia. Type II and III define mixed cryoglobulinemia. 40%
      approximately of patients with chronic hepatitis C virus (HCV) infection had
      cryoglobulinemia. OBJECTIVE: To evaluate the frequency of cryoglobulinemia in a
      chronic hepatitis virus (CHV) infection group and determine the characteristics
      of positive cryoglobulinemia patients. RESULTS: 76 patients were included. There
      were 53 women an 23 men. The mean age was 59.45 years. Mixed cryoglobulinemia was
      detected in 65 patients (85.5 %). Cirrhosis, old age and the long duration of CHV
      infection were the 3 factors associated with cryoglobulinemia positivity.
      CONCLUSION: Mixed cryoglobulinemia is a frequent manifestation during chronic
      hepatitis C infection virsus especially in patients with cirrhosis.

PMID- 16422363
TI  - [CD117 contribution in the diagnosic of mesenchymal tumors of the digestive
      tract].
AB  - Gastrointestinal stromal tumor (GIST) is a new distinct entity defined as CDI 17
      or c-kit positive mesenchymal tumors, originaling in gastrointestinal pacemaker
      cells known as interstitial cells of Cajal. This study evaluate the percentage of
      GIST previously diagnosed as mesenchymal tumors in our hospital during 11 years.
      METHODS: A total of 30 surgically resected gastrointestinal tumor specimens were
      collected from January 1990 to December 2000 in the pathology laboratory of la
      Rabta Jospital. Immunohistochemical studies were performed on these tumors with
      antibodies of CD 117, smooth muscle actin (SMA) and protein S-100. RESULTS: Among
      the 30 tumors, 26 (86.6%) were CD117 positive and were classified as
      gastrointestinal stromal tumors. Among the 26 GIST, SMA was positive in 11 tumors
      (42.3%), 6 tumors (23%) expressed protein S-100. The 4 tumors classified as non
      GIST were leiomyomas with the following immunohistochemical characteristics:
      CD117-negative with strong SMA-positive and protein S100 negative status.
      CONCLUSIONS: The majority (86.6%) of mesenchymal gastrointestinal tumors were
      GIST, except for a smalls groups of smooth muscle tumors.

PMID- 16422364
TI  - [Topical and systemic chemotherapy with 5-fluouracil in facial carcinoma
      secondary to xeroderma pigmentosum].
AB  - OBJECTIVE: to evaluate the feasibility, tolerance/toxicity and therapeutic
      efficacy of 5-fluorouracil (5-FU) by topical application and systemic use, in
      facial carcinoma associated with XP. METHODS AND PATIENTS: This is a prospective
      study of 10 patients with a median age of 22.9 years and a sex ratio of 4. Tumour
      lesions were facial mainly in the jugal and temporal region (36%). Chemotherapy
      indication was discussed in multidisciplinary committee, the topical 5
      fluorouracil was applied locally twice a day, whereas the systemic treatment
      consisted of FUFOL protocol (every 4 weeks a combinaison of a short perfusion of
      340 mg/m2 5-FU and preceded by an infusion of 20mg/m2 of folic acid, day 1 to 5);
      or C-FU protocol, combining continuous infusion of 5-FU (1 g/m2) 5 days
      associated with cisplatin (100 mg/m2, day 1) every 3 weeks. RESULTS: The median
      topical treatment duration was of 12 months in 10 patients. We noted a full
      tumoral regression in 10% of cases. Concerning systemic treatment, the median
      number of FUFOL cycles was 4 (2 to 6) and we observed a complete response in 6
      patients (60%), partial in 2 cases (20%). Treatment was well tolerated in most
      cases except for the cutaneous irritation on 5-FU application zone and a 4 grade
      cisplatin otoxicity. CONCLUSION: Systemic or topical chemotherapy represents an
      interesting palliative option for facial carcinoma associated with XP, avoiding
      reiterated surgery and its cosmetic consequences.

PMID- 16422365
TI  - [Abnormalities of haemostasis in myocardial infarction with normal coronary
      artery].
AB  - Myocardial infarction with normal coronary artery is ussually inaugural, with
      electric and clinical characteristics similar to those with atheroma. The role of
      constitutional or acquired abnormalities of haemostasis has been more
      incriminated in the pathogenesis of myocardial infarction with normal coronary.
      The aim of our study was to research abnormalities of haemostasis in patients
      with myocardial infarction and angiographically absolutely normal coronary
      arteries. PATIENTS AND METHODS: Thirty nine patients with myocardial infarction
      and normal coronary arteries where included in our study. They were 33 males and
      6 females aged between 22 and 75 years (44 + 13 years), in whom the deficiency in
      protein C and S. antithrombin, activated protein C resistance and
      antiphospholipid antibodies were assessed. RESULTS: Concurrent abnormalities of
      haemostasis were found in 10 patients: Antiphospholipid antibodies, found in 5
      patients constitute the most frequent abnormality. The other abnormalities were
      deficiency in protein C in two cases, deficiency in protein S 2 cases, deficiency
      in antithrombin in 2 ceses and activated protein C resistance in 3 cases .
      CONCLUSION: In our study. in face of the high prevalence of these abnormalities,
      it seems reasonable to research them, especially in young patients with
      myocardial infarction with normal coronary artery. This should have an impact on
      the management of these patients.

PMID- 16422367
TI  - [Stress echocardiography and mitral stenosis: what interest?].
AB  - The stress echocardiography is used extensively as a diagnostic and prognostic
      tool and the assessment of ischemic cardiopathies. Its use in valvulopathies is
      more limited, but is increasing with time. The discrepancies between the
      functional symptoms and hemodynamics at rest is frequently met in patients with
      mitral stenosis. By assessing changes of pressures, gradients and surface stress
      echocardiography helps to identify the real hemodynamic conditions permitting to
      recommend a more aggressive approach in certain situations.

PMID- 16422366
TI  - [Imaging of neuro-Behcet].
AB  - Behcet's disease is a vasculitis affecting predominantly the venous system. It's
      characterized by a classical triad of recurrent uveitis, oral and genital
      ulceration. Behcet's disease is more frequent in Japan, the Middle East and some
      Mediterranean countries. Its pathogenesis is still uncertain. Neurological
      manifestations in Behcet's disease are not rare and are associated with poor
      prognosis. These manifestations can be inaugural in 5% of cases and they are
      polymorphous. We report 15 new cases of neuro Behcet's disease explored by
      magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA).

PMID- 16422368
TI  - [Intra-uterine growth retardation: etiologic factors and management].
AB  - OBJECTIVE: The aim of this study is to define the etiologic factors, the
      diagnostic proceduresand obstetrical rules to be observed during a pregnancy in
      relation with low birth weight. PATIENTS AND METHODS: This is a retrospective
      study of 124 cases, carried out at the military hospital of Tunis, between
      January 1st 1999 and December 31 st 2001. RESULTS: The frequency of intra-uterine
      growth retardation (IVGR) was 2.1%. 46.8% of the patients were primiparous. The
      mean age of the patients was 30 years. 25.8% of the patients developed toxemia.
      The etiology was predominantly renovascular-syndromes, urinary infections, and
      idiopathic hypotrophy. The positive diagnosis was suggesred by the measure of the
      uterine height in 96% and was confirmed by sonogaphy in all cases. The ombilical
      Doppler was pathological in 17.76% of the cases. A corticosteroid administration
      for pulmonary maturation was prescribed in 28% of the cases. Obstetrical common
      rule was fetal extraction: 42.7% of the patients were delivered by cesarean.
      CONCLUSION: There is a real need to insist on the importance of early detection
      of fetal hypotrophy and of better management of the women at risk.

PMID- 16422369
TI  - [Tuberculous encapsulating peritonitis. About 18 cases].
AB  - Our goal is to study the circumstances of diagnosis and the therapeutic modes of
      encapsulating peritonitis of tubercular origin. We report in this retrospective
      study 18 cases of encapsulating peritonitis of tubercular origin collected from
      1982 to 2000. Symptoms and signs ere dominated by the general signs of tubercular
      nature, found isolated or in association with other, in 14 patients. Abdominal
      pain was found in all patients. Gastrointestinal disorders were found in 11
      patients. A typically sound abdominal mass was found in 3 cases. The
      ultrasonographic data associated with the biologic data, helped in making the
      diagnosis. Confirmation of the tubercular origin was provided by histological
      examination of the biopsies. Treatment was based on the anti-tuberculosis
      chemotherapy associating four antituberculous drugs taken daily during two months
      replated by the association of two antituberculous drugs during a period of six
      to 13 months. The outcome was favourable in 16 patients but the two patientsdied.
      Histological diagnosis and more rarely bacteriological examination, would be
      essential in order to start an early treatment. This diagnosis is confirmed by
      open coelioscopy when the ascitis is septated or by exploratory laparotomy in the
      fibro-adhesive formes. Radical surgery is indicated in case of complications.

PMID- 16422370
TI  - [Pseudo tumoral bronchial tuberculosis].
AB  - Bronchial lesion is a rare site for tuberculosis. It can mimic lung cancer
      especially when sputum- smear is negative, and this be a cause of a delay in
      diagnosis, that can be made later on by a culture of Koch bacillus or after a
      bronchial biopsy. Through these 4 cases reports, the authors recall the
      ethiopathogenic hypotheses of this lesion and review the radiologic, clinical and
      prognostic features of these unusual forms of TB.

PMID- 16422371
TI  - [Early gastric cancer--two case reports].
AB  - Gastric cancer is a serious disease with a high mortality rate. Early diagnosis
      of the disease improves its prognosis. We report two cases of early gastric
      cancer and we specify the clinical, endoscopic, histologic and therapeutic
      aspects of the disease. This study is about two female patients, respectively, 36
      and 70 years old. The diagnosis of early gastric cancer was based on pathologic
      examination of the resected stomach. The two patients are in remission 2 years
      and 6 months later, respectively. The diagnosis of early gastric cancer is often
      made on nonspecific symptoms. Oeso-gastro-duodenoscopy shows gastric mucosal
      anomalies. Pathologic examination of gastric biopsies confirm the diagnosis of
      adenocarcinoma. Endoscopic ultrasound is essential; it specifies the submucosal
      infiltration and evaluates the lymph node invasion. Surgery is the primary
      treatment but in some cases endoscopic mucosal resection provides good long-term
      results. Early diagnosis of adenocarcinoma improves the prognosis of the disease,
      which remains poor nowadays.

PMID- 16422372
TI  - [Malignant degeneration of mature benign teratoma of the ovary: a case report].
AB  - Malignant transformation of ovarian mature benign teratomas is an uncommon
      complication which often occurs in the postmenopausal period. Clinical
      presentation is similar to that of benign ovarian cysts. The diagnosis of
      malignant transformation is often made per-operatively by the break of the
      capsule and the adhesions of the tumor or during histological examination. The
      diagnosis is based on the association between a mature teratoma and a non
      metastatic unitissular, carcinoma or sarcoma. All histological forms can be met,
      but squamous cell carcinoma accounts for 75% of all cases. We report the case of
      a 70-year-old woman who had a squamous cell carcinoma which developed on a
      teratoma of the ovary, for whom the disease was fatal. The survival rate for this
      kind of ovarian tumour is reduced, with 15 to 30% survival after 5 years,
      irrespective of stages and histological types. Although it is not easy to define
      the best requested therapy, surgery associated with polychemotherapy or
      radiotherapy is apparently the only way of improving the poor prognosis for these
      tumours.

PMID- 16422373
TI  - [Urticarian vasculitis. A case report after sulfamethoxazoletrimethoprime
      ingestion].
AB  - Urticarian vasculitis (UV) is an anatomoclinical disorder characterized by the
      association of urticarian papules lasting for more than 24 hours with
      histological cutaneous vasculitis. Several etiologies are associated with the
      disease. We report the case of a 30-year-old woman with a-two-month history of
      urticarial purpuric and necrotic cutaneous lesions of the low limbs. These
      lesions occurred after oral sulfamethoxazole-trimethoprime ingestion, 2 weeks
      before the skin eruption. Histological examination revealed a leucocytoclasic
      vasculitis and direct immunofluorescence showed a perivascular IgG and C3
      deposits. Immunological, allergological and radiological investigations were
      normal. The pharmacological enquiry confirmed the imputability of
      sulfamethoxazole-trimethoprime in the onset of skin eruption. Mild cutaneous
      improvement was observed after 3 months of treatment with prednisone 0,5
      mg/Kg/day. Drug induced urticaria constitutes a rare etiology of UV.
      Sulfaminthoxazole-trimethoprime imputability has not been reported before among
      the drug responsible for UV. Management of patients is difficult and improvement
      usually occurs after several months because of the resistance of the skin
      lesions.

PMID- 16422374
TI  - [Chronic septic granulomatosis in children revealed by invasive pulmonary
      aspergillosis].
AB  - Chronic granulomatosis disease (GCD) is a hereditary abnormality of phagocytic
      cells, frequently revealed by invasive pulmonary Aspergillosis. The authors
      report the case of 8 year old girl investigates for hypotrophia, reccurent lung
      disease and hemoptysia. She was treated for pulmonary tuberculosis because of
      biological inflammatory syndrome, right alveolar opacity and positive tuberculin
      skin test. The course was marked by the developement of a thoracic wall mass.
      Anti- aspergillus serology was positive; culture of the thoracic mass puncture
      and bronchoalveolar lavage isolated fumigatus Aspergillus. GCD was suggested and
      confirmed by the NBT test.

PMID- 16422375
TI  - Losing the weight loss focus.

PMID- 16422376
TI  - Achieving healthy weights in children and adolescents.

PMID- 16422378
TI  - Lessons learned: morbid obesity patient care needs.

PMID- 16422377
TI  - A hybrid view of weight management.

PMID- 16422379
TI  - Reducing injury and death in teen drivers.

PMID- 16422381
TI  - Coding systems changes and the implications for the trauma registry.

PMID- 16422380
TI  - Management of hypothermia in the trauma patient.
AB  - Hypothermia is a disorder that causes catastrophic dysfunction in the body's
      regulation of homeostasis. Trauma patients are at increased risk of hypothermia
      from both intrinsic and iatrogenic causes. Rapid recognition and aggressive
      intervention is necessary to prevent organ failure and death. Passive external,
      active external, active core, and extracorporeal rewarming have all been studied
      as therapeutic options to manage severe hypothermia. Many, but not all, have a
      role in the resuscitation of hypothermic trauma patients. The appropriate
      rewarming modality should be chosen based on the patient, hemodynamic stability,
      and the resources available.

PMID- 16422382
TI  - A fungus among us: disseminated Aspergillosis.

PMID- 16422383
TI  - Going against the grain: a model for trauma registry operations.

PMID- 16422384
TI  - The ASK model: a bare bones approach to the critique of nursing research for use
      in practice.
AB  - Professional nurses are expected to read and evaluate nursing research. Many
      nurses' report feeling intimated by research studies. The Applicability, Science,
      Knowledge Model offers the basics needed to quickly review and grasp the
      potential clinical significance of a journal study. Using a research report
      previously published in the Journal of Trauma Nursing, the authors demonstrate
      the critique process. Key points for critical understanding and guidelines for
      application to practice are presented.

PMID- 16422385
TI  - Integration of concurrent trauma registry and performance improvement programs.
AB  - Health information management systems have had a tremendous impact on the
      delivery of healthcare. The implementation of an integrated, concurrent trauma
      registry and performance improvement system has had a remarkable impact on the
      University of Pennsylvania's trauma program. Having both the registry and
      performance improvement programs concurrent and integrated has allowed better
      utilization of staff and has produced more accurate, relevant and timely data.

PMID- 16422387
TI  - Acute extremity compartment syndrome.
AB  - Acute Extremity Compartment Syndrome is a disorder, which can cause loss of limb
      if left untreated. Compartment syndrome develops when pressures within the
      fascial compartments become elevated, resulting in decreased perfusion to muscles
      and nerves. Left untreated, tissue death occurs. Rapid identification of clinical
      signs can decrease severity of symptoms. Diligent nursing assessment and
      monitoring of clinical signs, with communication to the physician, will
      facilitate rapid treatment by the physician. The primary treatment option is
      early identification and intervention through performance of a fasciotomy.

PMID- 16422386
TI  - The top 10 things to evaluate in children with suspected blunt abdominal
      injuries.

PMID- 16422388
TI  - Carotid-cavernous sinus fistula in penetrating facial trauma.

PMID- 16422390
TI  - Basic protection of trauma registry information.

PMID- 16422389
TI  - The trauma disease.
AB  - Although trauma was identified as a "neglected disease" over three decades ago,
      it continues to remain the leading cause of death through the first four decades
      of life. Because trauma is preventable and frequently predictable, it is subject
      to the same epidemiology as disease. In the case of disease, the intervention of
      choice is prevention. By defining and addressing trauma as a disease, and
      approaching it within the context of behavioral nursing theory, the practitioner
      can develop interventions with the potential to reduce the impact and incidence
      of trauma across a wide spectrum of groups at identifiable risk.

PMID- 16422391
TI  - Collaborative model: nonoperative spleen and liver management.

PMID- 16422392
TI  - Cancer biology and hormesis: human tumor cell lines commonly display hormetic
      (biphasic) dose responses.
AB  - This article assesses the nature of the dose-response relationship of human tumor
      cell lines with a wide range of agents including antineoplastics, toxic
      substances (i.e., environmental pollutants), nonneoplastic drugs, endogenous
      agonists, and phyto-compounds. Hormetic-like biphasic dose responses were
      commonly reported and demonstrated in 136 tumor cell lines from over 30 tissue
      types for over 120 different agents. Quantitative features of these hormetic dose
      responses were similar, regardless of tumor cell line or agent tested. That is,
      the magnitude of the responses was generally modest, with maximum stimulatory
      responses typically not greater than twice the control, while the width of the
      stimulatory concentration range was usually less than 100-fold. Particular
      attention was directed to possible molecular mechanisms of the biphasic nature of
      the dose response, as well as clinical implications in which a low concentration
      of chemotherapeutic agent may stimulate tumor cell proliferation. Finally, these
      findings further support the conclusion that hormetic dose responses are broadly
      generalizable, being independent of biological model, endpoint measured, and
      stressor agent, and represent a basic feature of biological responsiveness to
      chemical and physical stressors.

PMID- 16422393
TI  - Cancer biology and hormesis: comments on Calabrese (2005).
AB  - Large numbers of chemicals of a variety of types exhibit apparent hormetic
      effects on cultured human cancer cells, causing stimulation of cell growth or
      related changes at low doses, followed by inhibition at higher doses. Many of the
      studies listed are not fully convincing, due to lack of appropriate controls or
      sufficient number of doses. However, the proposed hormetic response seems firmly
      established in a subset of these experiments. Significance with regard to in vivo
      cancer growth has not been pursued and must be a priority for the future. For
      several examples where in vivo titers are known, such as, resveratrol, suramin,
      and tamoxifen, comparison of the dose and concentration ranges confirms that
      hormesis could be an issue in vivo. Further investigations are warranted,
      especially for therapeutic drugs, phytochemicals, and environmental toxicants.

PMID- 16422394
TI  - Hormetic effects of hormones, antihormones, and antidepressants on cancer cell
      growth in culture: in vivo correlates.
AB  - Evidence is presented that the ability of hormones and antihormones to cause
      biphasic (hormetic) proliferative responses in cancer cells in vitro correlates
      with a similar effect of these substances in humans with cancer. Certain
      antidepressants also produce biphasic growth responses of cancer cells in vitro
      and stimulate cancer growth in rodents, correlating with an increased risk of
      breast and other cancers in some, but not all, epidemiological studies assessing
      early and/or late cancer incidence in patients on antidepressant drugs. The
      observation that certain drugs with biphasic effects on cancer cell growth in
      vitro may also produce an "up-down" effect on cancer growth in humans supports
      Calabrese's suggestion that the concept of the hormetic dose response must be
      taken seriously by toxicologists and regulators.

PMID- 16422395
TI  - Cancer biology and hormesis: commentary.
AB  - The observation of biphasic dose-response relationships following exposure to
      pharmacological and toxicological agents has been well documented. In this review
      Dr. Calabrese, using published data on human tumor cell lines treated with a
      variety of agents has provided additional support for the demonstration of
      hormesis in the cancer process. While this review has restricted the examination
      to human tumor cell lines, this limitation dose not take away from the value of
      the treatise and helps to point out the need for further analysis of the biphasic
      does response in other cancer models including in vivo carcinogenesis studies and
      human cancer epidemiology. This issue is further enhanced when the potential
      mechanisms for hormetic responses in the cancer cells are discussed, since the
      same mechanisms participate in the carcinogenesis process. Overall, this review
      provides an excellent opening examination into the definition of biphasic dose
      response effects of toxic and pharmacological agents in cancer cells.

PMID- 16422396
TI  - Nonlinear dose-effect relationship of different parameters in cancer cell lines.
AB  - The dose-effect curves of most parameters in cancer cell lines in response to x
      irradiation or toxic agents are usually nonlinear. Such a nature is demonstrated
      in this article with cell lines of the immune system. However, the shape of the
      nonlinear dose-effect curves was found to be different for lymphocytes (EL-4) and
      macrophages (J774A.1). The mechanisms and implications are briefly discussed.

PMID- 16422397
TI  - Commentary on "Cancer biology and hormesis: human tumor cell lines commonly
      display hormetic (biphasic) dose responses" by Edward J. Calabrese.

PMID- 16422398
TI  - The definition of hormesis and its implications for in vitro to in vivo
      extrapolation and risk assessment.
AB  - This article comments on some of the basic questions put forward in state-of-the
      art discussions on hormesis. There seems to be a need for a better definition of
      the concept itself and reconsideration of whether all biphasic dose-response
      curves should be considered representative for hormesis. Hormesis may be
      restricted to phenomena that proceed by mechanisms that are broadly generalizable
      and represent possibly beneficial overcompensation in response to an adverse
      stimulus. Using the concept that hormesis is defined as such, the biphasic effect
      of quercetin on cell proliferation, but also several other receptor-mediated
      biphasic dose-response phenomena, should not be related to hormesis. Taking into
      account hormesis in the procedures for risk assessment on compounds characterised
      by a threshold for the adverse effect is another matter for considerable debate.
      In our opinion, this would require the reduction of safety factors, providing the
      possibility for beneficial hormesis-type effects for some people, at the cost of
      increased chances on adverse effects for other parts of the population. Whether
      this is a proper way forward remains to be discussed. Improvement of risk
      assessment strategies may include taking into account biphasic dose-response
      curves, but should rather start with the consideration of proper physiologically
      based pharmacokinetic (PBPK) models for better extrapolation of differences in
      toxicokinetics going from high- to low-dose exposure, as well as taking into
      account kinetics for gene repair systems. Without considering in vivo
      toxicokinetics in the in vitro models, extrapolation from in vitro biphasic dose
      response curves on cell proliferation to in vivo cell proliferation is difficult
      to do. Altogether, it is concluded that hormesis is an important phenomenon,
      especially from the scientific point of view, but that its consequences for risk
      assessment and the possibilities for in vitro to in vivo extrapolation may remain
      limited without additional mechanistic insight.

PMID- 16422399
TI  - Stability of thick film piezoresistors under large pressure cycles at elevated
      temperature.
AB  - The resistance change of ruthenium based metal-insulator-metal (MIM) thick film
      resistors with hydrostatic pressure exhibits excellent linearity, no hysteresis,
      a small temperature dependency, and an order of magnitude greater sensitivity
      than the longitudinal mode. The effect of long-term 10(6) hydrostatic pressure
      cycles (0 to approximately 21 MPa) at 135 degrees C on response linearity,
      sensitivity (span), and the resistance at zero pressure Ro (offset) have been
      established for a commercial MIM composition. No change in linearity,
      sensitivity, and offset was observed up to 10(4) cycles. After 10(6) cycles the
      offset and sensitivity changed by less than 1% and 0.5%, respectively. Other
      parameters remained unchanged. The results are analyzed in terms of conduction
      models of this system.

PMID- 16422400
TI  - Analytical modeling of the apparent d33 piezoelectric coefficient determined by
      the direct quasistatic method for different boundary conditions.
AB  - The longitudinal piezoelectric coefficient d33 measured by the quasistatic
      (Berlincourt-type) method is strongly dependent on the sample aspect ratio
      (thickness/lateral dimension) and the type of contacts used to collect the charge
      and apply the pressure on the sample. In this study, we present an analytical
      model in which apparent (measured) d33 is a function of the aspect ratio, the
      mechanical properties of contacts, and the properties of piezoelectric material.
      Using derived relations, it is possible to obtain the true value of d33 in the
      wide range of boundary conditions. The analytical results are compared with
      simulations using finite element modeling (FEM) and with experimental data; and
      good correlation is found among them. Effect of the geometry of the contacts on
      apparent d33 value is specifically addressed.

PMID- 16422401
TI  - Absolute calibration of a geodetic time transfer system.
AB  - An absolute calibration technique is developed for geodetic Global Positioning
      System (GPS) receivers. An uncertainty budget for the system (receiver, cables,
      connectors, antenna) is evaluated, yielding 1.1 ns at each frequency, and 1.6 ns
      for a two-receiver experiment. Analysis of data on a short baseline yields 0.8
      and 1.2 ns agreement on P1 and P2, respectively.

PMID- 16422402
TI  - Long-term comparisons between two-way satellite and geodetic time transfer
      systems.
AB  - Global Positioning System (GPS) observations recorded in the United States and
      Europe were used to evaluate time transfer capabilities of GETT (geodetic time
      transfer). Timing estimates were compared with two-way satellite time and
      frequency transfer (TWSTFT) systems. A comparison of calibrated links at the U.S.
      Naval Observatory, Washington, D.C., and Colorado Springs, CO, yielded agreement
      of 2.17 ns over 6 months with a standard deviation of 0.73 ns. An uncalibrated
      link between the National Institute of Standards and Technology (NIST) and
      Physikalisch-Technische Bundesanstalt, Braunschweig, Germany, has a standard
      deviation of 0.79 ns over the same time period.

PMID- 16422403
TI  - A novel microcomputer temperature-compensating method for an overtone crystal
      oscillator.
AB  - In this paper, a novel microcomputer temperature-compensating method for an
      overtone crystal oscillator (MCOXO) is presented. In this method, a ceramic
      oscillator is chosen, and its output frequency is mixed with the output frequency
      of an overtone crystal oscillator. A crystal filter is used to suppress the
      spurious mixing products. A microcomputer is used to control the switch
      capacitance array that is connected to the ceramic oscillator circuit. The
      frequency deviation of the crystal oscillator is directly compensated by the
      output frequency of the ceramic oscillator. As a result, the method is able to
      overcome the disadvantages of frequency stability degradation and phase noise
      deterioration that are provoked by adding inductance or frequency multiplication
      in traditional compensating approaches. At the same time, this method is able to
      compensate a quite wide frequency range and many types of oscillators, not just
      crystal oscillators. The experimental compensating results show that, using this
      method, the frequency-temperature stability of a 100 MHz 5th overtone temperature
      compensated crystal oscillator can achieve < or = +/-2 x 10(-6) for 0-70 degrees
      C.

PMID- 16422404
TI  - Low-noise electronic design for the 87Rb coherent population trapping maser.
AB  - In this paper we present the low-noise electronics for a prototype of rubidium
      maser based on the coherent population trapping (CPT) phenomenon. After an
      overview of the general architecture, we will focus our description on the main
      blocks of the equipment we implemented: the microwave synthesis chain, the
      detection apparatus, the clock servo system and the electronics devoted to
      control the laser and the temperature. For each part, we present the design, the
      implementation, and the characterization measurements we performed. The
      contribution to the CPT maser frequency stability of each part also has been
      evaluated, and the frequency stability of the clock is reported.

PMID- 16422405
TI  - Propagation of spontaneously actuated pulsive vibration in human heart wall and
      in vivo viscoelasticity estimation.
AB  - Though myocardial viscoelasticity is essential in the evaluation of heart
      diastolic properties, it has never been noninvasively measured in vivo. By the
      ultrasonic measurement of the myocardial motion, we have already found that some
      pulsive waves are spontaneously excited by aortic-valve closure (AVC) at end
      systole (T0). These waves may serve as an ideal source of the intrinsic heart
      sound caused by AVC. In this study, using a sparse sector scan, in which the beam
      directions are restricted to about 16, the pulsive waves were measured almost
      simultaneously at about 160 points set along the heart wall at a sufficiently
      high frame rate. The consecutive spatial phase distributions, obtained by the
      Fourier transform of the measured waves, clearly revealed wave propagation along
      the heart wall for the first time. The propagation time of the wave along the
      heart wall is very small (namely, several milliseconds) and cannot be measured by
      conventional equipment. Based on this phenomenon, we developed a means to measure
      the myocardial viscoelasticity in vivo. In this measurement, the phase velocity
      of the wave is determined for each frequency component. By comparing the
      dispersion of the phase velocity with the theoretical one of the Lamb wave (the
      plate flexural wave), which propagates along the viscoelastic plate (heart wall)
      immersed in blood, the instantaneous viscoelasticity is determined noninvasively.
      This is the first report of such noninvasive determination. In in vivo
      experiments applied to five healthy subjects, propagation of the pulsive wave was
      clearly visible in all subjects. For the 60-Hz component, the typical propagation
      speed rapidly decreased from 5 m/s just before the time of AVC (t = T0 - 8 ms) to
      3 m/s at t = T0 + 10 ms. In the experiments, it was possible to determine the
      viscosity more precisely than the elasticity. The typical value of elasticity was
      about 24-30 kPa and did not change around the time of AVC. The typical transient
      values of viscosity decreased rapidly from 400 Pa x s at t = T0 - 8 ms to 70 Pa x
      s at t = T0 + 10 ms. The measured shear elasticity and viscosity in this study
      are comparable to those obtained for the human tissues using audio frequency in
      in vitro experiments reported in the literature.

PMID- 16422406
TI  - Stress field forming of sector array transducers for vibro-acoustography.
AB  - This paper presents a study of the stress field forming of sector array
      transducers for vibro-acoustography applications. The system point-spread
      function (PSF) is given in terms of the dynamic radiation stress exerted on a
      point target by a dual ultrasound beam with slightly different frequencies. The
      radiation stress is calculated by assuming that the resulting ultrasound beam is
      a plane wave. The stress is proportional to the product of the velocity potential
      of each incident ultrasound beam. The beamforming and stress field forming of
      sector array transducers are analyzed through linear acoustics. An expression for
      the velocity potential produced by sector array transducers is derived. The vibro
      acoustography PSF is evaluated numerically. A comparison between the PSF of a
      sector array and a confocal transducers is presented. The compared
      characteristics of the PSF are sidelobe levels, transverse, and in-depth spatial
      resolution. Indeed, one motivation to study sector transducers is the fact the
      depth-of-field of these transducers should be smaller than that of same size
      confocal transducers. An experimental setup was used to validate the theoretical
      PSF of sector array transducers. Results show that the measured PSF is in good
      agreement with the theoretical predications. Vibro-acoustography images of a
      breast-phantom by both transducers are presented and discussed.

PMID- 16422407
TI  - Quantitative real-time blood flow estimation with intravascular ultrasound in the
      presence of in-plane flow.
AB  - Previously, we showed a source of error in blood flow estimation introduced by in
      plane flow using a slow-time finite-impulse response (FIR) filter-bank method
      measuring blood flow through the image plane of an intravascular ultrasound
      (IVUS) catheter array. There is a monotonic relationship between flow velocity
      and the normalized second moment of the slow-time spectrum when flow is
      orthogonal to the image plane of a side-looking catheter array. However, this
      relationship changes in the presence of in-plane flow, as slow-time spectra shift
      and spread with varying in-plane and out-of-plane components. These two effects
      increase the normalized spectral second moment, resulting in flow overestimates.
      However, by resampling the received signal with variable time delay from pulse to
      pulse (i.e., tilting the slow-time signals), the slow-time spectrum shifts back
      to direct current (DC), and the orthogonal estimation method can be used. We
      present a method to correct this overestimation and accurately estimate blood
      flow through the image plane in real time. Initially, the tilt delay needed to
      shift the slow-time spectrum back to DC at each point within the flow field is
      calculated. Knowing this tilt delay, a tilted slow-time signal is obtained for
      the velocity component normal to the image plane, and its spectrum is estimated
      using a filter-bank. That spectrum then is used to estimate the flow speed using
      a mapping function closely related to the monotonic relationship between the slow
      time spectrum and flow speed observed for orthogonal flow. To accurately estimate
      flow angles, we modified the filter-bank algorithm, applying slow-time filter
      coefficients in a tilted arrangement and studying the slow-time spectral energy
      as a function of tilt. The slow-time spectral estimate is constructed with the
      tilted output of eight narrow, band-pass filters from a filter-bank. Independent
      simulations show that, for blood slowing at angles between +/-6 degrees and +/-15
      degrees at a speed of 300 mm/s, flow velocity would be overestimated by as much
      as 38.79% and 249%, respectively, using the direct filter-bank approach. However,
      this error can be corrected using the modified method presented here, reducing
      the maximum overestimation error by a factor of 2.69 and 10.88 for those angles,
      respectively. Although the remaining error is not negligible, the volume flow
      rate, calculated by integrating the flow velocity over the entire vessel lumen,
      differs by only 3% or less from the true value over the angular range considered
      here. This represents an improvement of a factor of 40 over uncompensated
      estimates at maximum flow angles. Consequently, the modified real-time method can
      quantitatively measure flow in most IVUS applications in which the catheter's
      image plane is not precisely orthogonal to the flow direction.

PMID- 16422408
TI  - Acoustic detection of controlled laser-induced microbubble creation in gelatin.
AB  - A high-frequency (85 MHz) acoustic technique is used to identify system
      parameters for controlled laser-induced microbubble creation inside tissue
      mimicking, gelatin phantoms. Microbubbles are generated at the focus of an
      ultrafast 793-nm laser source and simultaneously monitored through ultrasonic
      pulse-echo recordings. Displayed in wavefield form, these recordings illustrate
      microbubble creation, and integrated backscatter plots provide specifics about
      microbubble characteristics and dissolution behavior. By varying laser
      parameters, including pulse fluence (or pulse energy flux, J/cm2), total number
      of pulses delivered, and the period between pulses, the size, lifetime, and
      dissolution dynamics of laser-induced microbubbles may be independently
      controlled. Pulse fluence is the main size-controlling parameter, whereas both
      increases in pulse fluence and pulse number can lengthen microbubble lifetime
      from tens to hundreds of milliseconds. In short, a microbubble of particular
      lifetime does not necessarily have to be of a particular size. Microbubble
      behavior, furthermore, is independent of pulse periods below a fluence-dependent
      threshold value, but it exhibits stochastic behavior if pulse repetition is too
      slow. These results demonstrate that laser pulse fluence, number, and period may
      be varied to deposit energy in a specific temporal manner, creating and
      stabilizing microbubbles with particular characteristics and, therefore,
      potential uses in sensitive acoustic detection and manipulation schemes.

PMID- 16422409
TI  - Aberration correction by nonlinear beam mixing: generation of a pseudo point
      sound source.
AB  - Nonlinear beam mixing with microbubbles was explored to create a pseudo point
      source for aberration correction of therapeutic ultrasound. A damping coefficient
      for a bubble driven by a dual frequency sound field was derived by revisiting
      Prosperetti's linearized damping model. As a result, the overall damping term for
      dual frequency was obtained by linear summation of two damping terms for each
      frequency. The numerical simulation based on the bubble model suggests that the
      most efficient size range to generate a 1 MHz frequency from 4 MHz and 5 MHz
      sound sources is 2.6 to 3.0 microm. Furthermore, this size range constitutes the
      primary distribution of a specific ultrasound contrast agent. When a chamber of
      0.1% of the diluted agent is sonified by 4 MHz and 5 MHz sound beams with 80
      degrees incident angle between them, an approximately 100 Pa, 1 MHz difference
      frequency signal can be measured approximately 10 cm away. In addition, the
      received 1 MHz difference frequency signal shows omni-directional
      characteristics, even though the overlap zone of the two sound beams is on the
      order of the difference frequency wavelength. Therefore, the induced sound source
      can be considered as a pseudo point source and is expected to be useful for
      aberration correction for therapeutic ultrasound.

PMID- 16422410
TI  - High-frequency dynamics of ultrasound contrast agents.
AB  - Ultrasound contrast agents enhance echoes from the microvasculature and enable
      the visualization of flow in smaller vessels. Here, we optically and acoustically
      investigate microbubble oscillation and echoes following insonation with a 10 MHz
      center frequency pulse. A high-speed camera system with a temporal resolution of
      10 ns, which provides two-dimensional (2-D) frame images and streak images, is
      used in optical experiments. Two confocally aligned transducers, transmitting at
      10 MHz and receiving at 5 MHz, are used in acoustical experiments in order to
      detect subharmonic components. Results of a numerical evaluation of the modified
      Rayleigh-Plesset equation are used to predict the dynamics of a microbubble and
      are compared to results of in vitro experiments. From the optical observations of
      a single microbubble, nonlinear oscillation, destruction, and radiation force are
      observed. The maximum bubble expansion, resulting from insonation with a 20
      cycle, 10-MHz linear chirp with a peak negative pressure of 3.5 MPa, has been
      evaluated. For an initial diameter ranging from 1.5 to 5 microm, a maximum
      diameter less than 8 microm is produced during insonation. Optical and acoustical
      experiments provide insight into the mechanisms of destruction, including
      fragmentation and active diffusion. High-frequency pulse transmission may provide
      the opportunity to detect contrast echoes resulting from a single pulse, may be
      robust in the presence of tissue motion, and may provide the opportunity to
      incorporate high-frequency ultrasound into destruction-replenishment techniques.

PMID- 16422411
TI  - Influence of lipid shell physicochemical properties on ultrasound-induced
      microbubble destruction.
AB  - We present the first study of the effects of monolayer shell physicochemical
      properties on the destruction of lipid-coated microbubbles during insonification
      with single, one-cycle pulses at 2.25 MHz and low-duty cycles. Shell cohesiveness
      was changed by varying phospholipid and emulsifier composition, and shell
      microstructure was controlled by postproduction processing. Individual
      microbubbles with initial resting diameters between 1 and 10 microm were isolated
      and recorded during pulsing with bright-field and fluorescence video microscopy.
      Microbubble destruction occurred through two modes: acoustic dissolution at 400
      and 600 kPa and fragmentation at 800 kPa peak negative pressure. Lipid
      composition significantly impacted the acoustic dissolution rate, fragmentation
      propensity, and mechanism of excess lipid shedding. Less cohesive shells resulted
      in micron-scale or smaller particles of excess lipid material that shed either
      spontaneously or on the next pulse. Conversely, more cohesive shells resulted in
      the buildup of shell-associated lipid strands and globular aggregates of several
      microns in size; the latter showed a significant increase in total shell surface
      area and lability. Lipid-coated microbubbles were observed to reach a stable size
      over many pulses at intermediate acoustic pressures. Observations of shell
      microstructure between pulses allowed interpretation of the state of the shell
      during oscillation. We briefly discuss the implications of these results for
      therapeutic and diagnostic applications involving lipid-coated microbubbles as
      ultrasound contrast agents and drug/gene delivery vehicles.

PMID- 16422412
TI  - Evaluation of the spectral fit algorithm as functions of frequency range and
      deltakaeff.
AB  - Considerable effort has been directed at quantifying the properties of the tissue
      microstructure (i.e., scatterer correlation length) to diagnose disease and
      monitor treatment. In vivo assessments have had limited success due to frequency
      dependent attenuation along the propagation path (i.e., total attenuation)
      masking the frequency dependence of the scattering from the tissue
      microstructure. Previously, both total attenuation and scatterer correlation
      length, given by the effective radius, were solved simultaneously by a two
      parameter minimization of the mean squared error between a reference spectrum,
      modified by the attenuation and scatterer effective radius, and the backscattered
      waveforms using an algorithm termed the spectral fit algorithm. Herein, the
      impact of frequency range (largest frequency minus smallest frequency) and
      deltakaeff (largest kaeff value minus smallest kaeff value; k is wave number and
      aeff is scatterer effective radius) used by the spectral fit algorithm on
      estimating the scatterer effective radius, and total attenuation was assessed by
      computer simulations while excluding frequencies of the backscattered power
      spectrum dominated by electronic noise. The simulations varied the effective
      radius of the scatterers (5 microm to 150 microm), the attenuation of the region
      (0 to 1 dB/cm-MHz), the bandwidth of the source, and the amount of electronic
      noise added to the radio frequency (rf) waveforms. The center frequency of the
      source was maintained at 8 MHz. Comparable accuracy and precision of the
      scatterer effective radius were obtained for all the simulations whenever the
      same deltakaeff was used to obtain the estimates. A deltakaeff of 1 gave an
      accuracy and precision of approximately 15% +/- 35%, and a width of 1.5 gave an
      accuracy and precision of approximately 5% +/- 15% consistently for all of the
      simulations. Similarly, the accuracy and precision of the total attenuation
      estimate were improved by increasing the frequency range used by the spectral fit
      algorithm.

PMID- 16422413
TI  - Ultrasonic computed tomography reconstruction of the attenuation coefficient
      using a linear array.
AB  - The attenuation coefficient distribution and sound velocity distribution in the
      breast can be used to complement B-mode ultrasound imaging in the detection of
      breast cancer. This study investigated an approach for reconstructing the
      attenuation coefficient distribution in the breast using a linear array. The
      imaging setup was identical to that for conventional B-mode breast imaging, and
      the same setup has been used for reconstruction of sound velocity distributions
      in previous studies. In this study, we further developed a reconstruction method
      for the attenuation coefficient distribution. In particular, the proposed method
      incorporates the segmentation information from B-mode images and uses the sound
      velocity distribution to compensate for refraction effects. Experiments were
      conducted with a setup consisting of a 5-MHz, 128-channel linear array, a
      programmable digital array system, a phantom, and a computer. The constructed
      phantom contained materials mimicking the following breast tissues: glandular
      tissue, fat, cysts, high-attenuation tumors, and irregular tumors. Application of
      the proposed technique resulted in all the cysts and tumors (including high
      attenuation and irregular tumors) being distinguished by thresholding the
      reconstructed attenuation coefficients. We have demonstrated that it is possible
      to use the same imaging setup to acquire data for B-mode image, sound velocity
      distribution, and attenuation coefficient distribution simultaneously. Moreover,
      the experimental data indicate its potential in improving the detection of breast
      cancer.

PMID- 16422414
TI  - The determination of the optimal length of crystal blanks in quartz crystal
      resonators.
AB  - It is well understood that the strong coupling of thickness-shear and flexural
      vibrations in piezoelectric crystal plates only occurs at specific length at
      which the vibration mode conversion, like the flexural mode gradually converting
      to thickness-shear mode while the thickness-shear mode converting to higher-order
      flexural mode, happens. It is important to avoid the strong coupling of modes in
      a crystal resonator that uses thickness-shear vibrations to enhance the energy
      trapping. To achieve such a design goal, the length of a crystal blank should be
      carefully chosen such that the coupling is at its weakest, which usually is in
      the middle of two strong coupling points. Through a closer examination of the
      frequency spectra, or the frequency-length relationship in this study, we can see
      that the strong coupling points appear periodically. This implies that we can
      find exact locations with the plate theory that predicts the resonance frequency.
      Based on this observation, we first use the first-order Mindlin plate theory with
      the precise thickness-shear frequency, which is normalized to one, to find
      corresponding wavenumbers. Then the length as a variable is solved from the
      coupled frequency equation for exact coupling points in a crystal plate of AT-cut
      quartz. The optimal length of a crystal blank in the simplest resonator model is
      calculated for the coupled thickness-shear, flexural, and extensional vibrations.
      The solutions and the method will be important in the determination of optimal
      length of a crystal blank in the resonator design process.

PMID- 16422415
TI  - Vibrations of an asymmetrically electroded piezoelectric plate.
AB  - Two-dimensional equations for coupled extensional, flexural, and thickness-shear
      motions of a piezoelectric plate are obtained systematically from the three
      dimensional equations of linear piezoelectricity by retaining lower order terms
      in power series expansions in the plate thickness coordinate. The plate can have
      asymmetric electrodes on its major surfaces. The equations are specialized to
      crystals of 6-mm symmetry and are used to analyze thickness-shear vibrations of
      an asymmetrically electroded plate. Energy trapping, a behavior of thickness
      shear modes crucial to applications, is examined.

PMID- 16422416
TI  - Fast scanning probe for ophthalmic echography using an ultrasound motor.
AB  - High-frequency transducers, up to 35-50 MHz, are widely used in ophthalmic
      echography to image fine eye structures. Phased-array techniques are not
      practically applicable at such a high frequency, due to the too small size
      required for the single transducer element, and mechanical scanning is the only
      practical alternative. At present, all ophthalmic ultrasound systems use focused
      single-element, mechanically scanned probes. A good probe positioning and image
      evaluation feedback requires an image refresh-rate of about 15-30 frames per
      second, which is achieved in commercial mechanical scanning probes by using
      electromagnetic motors. In this work, we report the design, construction, and
      experimental characterization of the first mechanical scanning probe for
      ophthalmic echography based on a small piezoelectric ultrasound motor. The
      prototype probe reaches a scanning rate of 15 sectors per second, with very
      silent operation and little weight. The first high-frequency echographic images
      obtained with the prototype probe are presented.

PMID- 16422418
TI  - Design and characteristic analysis of L1B4 ultrasonic motor considering contact
      mechanism.
AB  - Up to the present time, the analysis and design of ultrasonic motors (USMs) have
      been performed using rough analytic methods or commercial analysis tools without
      considering the complex contact mechanisms. As a result, it was impossible to
      achieve an exact analysis and design of a USM. In order to address the problem,
      we proposed the analysis and design methodology of an L1B4 USM using a three
      dimensional finite element method combined with an analytic method that considers
      complex contact mechanisms in linear operation. This methodology is applicable to
      many other kinds of USMs which use resonance modes and contact mechanisms. Also,
      we designed and prototyped the mechanical system and driving circuit of the L1B4
      USM, and finally validated the proposed analysis and design methodology by
      comparing their outcomes with experimental data.

PMID- 16422417
TI  - A novel, single-mode piezoceramic plate actuator for ultrasonic linear motors.
AB  - A new type of piezoelectric plate actuator for ultrasonic linear motors has been
      developed. These new piezoelectric actuators use the principle of asymmetric
      resonant excitation of the piezoceramic plate in a special resonant mode
      consisting of a standing two-dimensional extensional wave in a piezoceramic
      plate. The behavior of the actuator has been simulated with finite-element method
      (FEM) software and the simulation results checked with single-point contact
      measurements on the surface of the actuator. This paper describes this work and
      closes by describing the new ultrasonic translation stages based on this design.

PMID- 16422420
TI  - Investigation on SAW properties of LGS and optimal cuts for high-temperature
      applications.
AB  - A promising perspective for surface acoustic wave (SAW) device applications at
      high temperature has been opened by langasite (LGS). The SAW properties of LGS in
      singly and doubly rotated cuts at 250 degrees C are investigated. Three
      noticeable regions for SAW-cut orientations and propagation directions at high
      temperature are put forward and are defined by Euler angles [0 degrees, 20
      degrees --> 50 degrees, 35 degrees --> 45 degrees], [0 degrees, 85 degrees -->
      110 degrees, 0 degrees --> 5 degrees], and [0 degrees, 138 degrees --> 145
      degrees, 20 degrees --> 23 degrees], respectively. The first region includes zero
      or comparatively reduced temperature coefficient of delay (TCD) (<2 ppm) and
      smaller electromechanical coupling factor (K2) (0.2%-0.35%); the second one
      exhibits higher K2 (0.35%-0.45%) and moderate TCD (<5 ppm); and the highest K2
      (>0.45%) and larger TCD (25-30 ppm) characterize the last region. For some
      typical orientations within the above-mentioned three regions, the temperature
      dependency of SAW characteristics (up to 1000 degrees C) is discussed. The second
      region [0 degrees, 85 degrees --> 110 degrees, 0 degrees --> 5 degrees],
      especially the orientation [0 degrees, 90 degrees, 0 degrees], has better
      comprehensive characteristics of SAW and is more suitable for high-temperature
      applications. Therefore, we should give a top priority to the orientation [0
      degrees, 90 degrees, 0 degrees] in the design of SAW devices operating at high
      temperature. Comparison between published experimental results and numerical
      predictions based on LGS constants and their temperature coefficients available
      in the literature reveals that the theoretical results of TCD under 250 degrees C
      are in agreement with the experimental ones (the relative error of TCD is within
      10%).

PMID- 16422419
TI  - Tomographic imaging of an ultrasonic field in a plane by use of a linear array:
      theory and experiment.
AB  - Quantitative ultrasonic characterization of in-homogeneous and anisotropic
      materials is often difficult due to undesired phenomena such as beam steering and
      phase aberration of the insonifying field. We introduce a method based on
      tomographic reconstruction techniques for the visualization of an ultrasonic
      field using a linear array rotated in a plane. Tomographic reconstruction of the
      ultrasonic field is made possible through the phase-sensitive nature of the tall,
      narrow piezoelectric elements of a linear array that act as parallel line
      integrators of the pressure field. We validate the proposed imaging method
      through numerical simulations of propagated ultrasonic fields based upon the
      angular spectrum decomposition technique. We then demonstrate the technique with
      experimental measurements of two textile composites and a reference water path.
      We reconstruct images of the real and imaginary parts of a transmitted 2 MHz
      ultrasonic field that are then combined to reconstruct images of the power and
      unwrapped phase. We also construct images of the attenuation and phase shift for
      several regions of the composites. Our results demonstrate that tomographic
      imaging of an ultrasonic field in a plane using a rotated linear array can
      potentially improve ultrasonic characterization of complex materials.

PMID- 16422421
TI  - X-ray topography analysis of acoustic wave fields in the SAW-resonator
      structures.
AB  - The formation of fields of standing surface acoustic waves (SAW) in LiNbO3 and
      La3Ga5SiO14 (LGS) crystals was studied by high-resolution topography method on a
      laboratory X-ray source. The fields of standing SAW were formed using SAW
      resonator structures consisting of interdigital transducer (IDT) and reflecting
      gratings. The SAW amplitudes and power flow angles were measured by X-ray
      topography, diffraction in acoustic beam was visualized, and the SAW interaction
      with the crystal structure defects was studied.

PMID- 16422422
TI  - Comparison and electrical modeling of new polymeric cellular electrets.
AB  - A new family of cellular polymers-that, upon appropriate charging, reveals
      interesting piezoelectric properties-has been developed recently. Its major
      characteristic is thermal stability up to high temperatures, which broadens the
      potential field of application. These materials become electrets upon charging
      under high levels of electric field. Investigation of charging mechanisms is
      fundamental to reach optimization of electret and piezoelectric properties. This
      paper presents results and considerations relevant to contact charging of these
      new materials, pointing out the relation between partial discharge and space
      charge formation, as well as time and temperature stability of electret
      properties. The concepts of threshold for partial discharge inception and space
      charge accumulation, the modeling of avalanches in cavities, and the rate of
      charge generation are exploited trying to explain charging mechanism and,
      therefore, they provide useful indication for optimization of material
      manufacturing.

PMID- 16422423
TI  - Design and fabrication of broadband graded ultrasonic transducers with
      rectangular kerfs.
AB  - Broadband ultrasound imaging is capable of achieving superior resolution in
      clinical applications. An effective and easy way of manufacturing broadband
      transducers is desired for these applications. In this work, a graded material in
      which the piezoelectric plate is mechanically graded with rectangular grooves is
      introduced. Finite element analysis (FEA) demonstrated that the graded
      piezoelectric material could achieve a broadband, time-domain response resulting
      from multiple resonant modes. Experimental tests were carried out to validate
      these theoretical results. Based upon the FEA designs, several single-element
      transducers were fabricated using either a nondiced ceramic or a diced, graded
      ceramics. A superior bandwidth of 92% was achieved by the graded transducer when
      compared to a bandwidth of 56% produced by the nondiced ceramic transducer at the
      expense of a reduced sensitivity.

PMID- 16422424
TI  - Generation and detection of guided waves using PZT wafer transducers.
AB  - We report here the use of finite element simulation and experiments to further
      explore the operation of the wafer transducer. We have separately modeled the
      emission and detection processes. In particular, we have calculated the wave
      velocities and the received voltage signals due to A0 and S0 modes at an output
      transducer as a function of pulse center frequency. These calculations include
      the effects of finite pulse width, pulse dispersion, and the detailed interaction
      between the piezoelectric element and the transmitting medium. We show that the
      received signals for A0 and S0 modes have maxima near the frequencies predicted
      from the previously published point-force model.

PMID- 16422425
TI  - Variational principles for the equations of porous piezoelectric ceramics.
AB  - The governing equations of a porous piezoelectric continuum are presented in
      variational form, though they were well established in differential form.
      Hamilton's principle is applied to the motions of a regular region of the
      continuum, and a three-field variational principle is obtained with some
      constraint conditions. By removing the constraint conditions that are usually
      undesirable in computation through an involutory transformation, a unified
      variational principle is presented for the region with a fixed internal surface
      of discontinuity. The unified principle leads, as its Euler-Lagrange equations,
      to all the governing equations of the region, including the jump conditions but
      excluding the initial conditions. Certain special cases and reciprocal
      variational principles are recorded, and they are shown to recover some of the
      earlier ones.

PMID- 16422426
TI  - A method of "weak resonance" for quality factor and coupling coefficient
      measurement in piezoelectrics.
AB  - In the absolute-immittance spectrum of a piezoelectric resonator (PR), if the
      relative resonance-antiresonance frequency interval of a high-intensity resonance
      is basically determined by the coefficient of electromechanical coupling (CEMC),
      the relative resonance-antiresonance frequency interval of a low-intensity
      resonance with the resonance-antiresonance attenuation less than 15 dB,
      regardless of the reason, is determined by the quality factor Q of the resonance,
      and its intensity is proportional to the CEMC. The technique for the quality
      factor and CEMC determination based on the "weak resonance" (WR) concept has been
      formulated and then applied to low-Q and/or low-CEMC piezoelectrics, including
      the initial stage of piezoceramics polarization, and to piezotransducers under
      electrical or mechanical loading with maximum efficiency. The WR method allows
      one to determine the quality factor on PRs under specific conditions, such as
      arbitrary PR shape resulting to a broken frequency spectrum; PRs with an
      extremely large or extremely low electrical capacitance; at high-order PR
      harmonics; electrodeless piezoelements under mechanically contactless electrical
      excitation; determining the local thickness-mode material quality factor value
      and its distribution along the surface of a thin electrodeless piezoplate--all
      this where the traditional methods show a poor performance or do not work at all.

PMID- 16422427
TI  - Elastic, piezoelectric, and dielectric characterization of modified BiScO3-PbTiO3
      ceramics.
AB  - The perovskite solid solution system (1-x)BiScO3-(x)PbTiO3 represents an
      interesting new family of high-temperature piezoelectric materials. Compositions
      near the morphotropic phase boundary (x approximately 0.64) have been reported to
      have high Curie temperatures (Tc > 450 degrees C) and good piezoelectric
      coefficients (d33 approximately 460 pC/N). In this work, manganese additions were
      used to improve the high-temperature electrical resistivity and RC time constant
      of compositions near the morphotropic phase boundary. The addition of manganese
      was found to shift Tc to slightly lower temperatures (442 degrees C and 456
      degrees C for x = 0.64 and x = 0.66, respectively). The piezoelectric activities
      of the modified materials were found to be reduced slightly due to the hardening
      effect of manganese; however, the temperature stability and resistivity of the
      modified materials were significantly enhanced. In this paper we present, for the
      first time, a complete set of materials constants, including the elastic (sij,
      cij), piezoelectric (dij, eij, gij, hij), dielectric (epsilonij, betaij), and
      electromechanical (kij) coefficients and compare them to both unmodified
      0.36BiScO3-0.64PbTiO3 and PZT5A ceramics.

PMID- 16422428
TI  - Characteristics of (1010) and (1120) textured ZnO piezofilms for a shear mode
      resonator in the VHF-UHF frequency ranges.
AB  - This paper reports the fabrication and characterization of ZnO piezoelectric thin
      films in which the crystallite c-axis is unidirectionally aligned in the plane.
      The films were deposited by a conventional radio frequency (RF) magnetron
      sputtering apparatus without epitaxy. We have measured reflection coefficient S11
      of the ZnO film/glass substrate composite shear mode resonator and confirmed that
      the resonator excites shear wave only in the very high frequency to ultra high
      frequency ranges (VHF-UHF). The crystallites c-axis orientation and alignment
      were determined by x-ray diffraction (XRD) patterns, phi-scan pole figure
      analysis, omega-scan rocking curves, and atomic force microscope (AFM)
      measurement. The transduction of the shear wave showed good agreement with
      properties of the crystallite alignment in the film.

PMID- 16422429
TI  - Vibration of piezoelectric/elastic laminated trimorph ring transducer.
AB  - This article describes the vibration characteristics of the trimorph ring
      transducer that consists of an isotropic elastic ring laminated between two
      identical piezoelectric rings under mechanical traction-free and constant
      electric voltage boundary conditions. The electro-elasticity theory with
      Kirchhoff-Love plate theory was applied to formulate the electromechanical
      solution. The resonance, antiresonance frequencies with corresponding mode shapes
      were verified by the measured impedance frequency responses. And, the design of
      maximized electromechanical coupling coefficients (EMCC) is proceeded.

PMID- 16422430
TI  - New studies examine the impact of performance measures.

PMID- 16422431
TI  - JCAHO, AHA clash on performance data.

PMID- 16422432
TI  - New CMS guidelines for managing complaints.

PMID- 16422433
TI  - Strategies to ease data collection burden.

PMID- 16422434
TI  - System achieves 'right patient, right level of care'.

PMID- 16422435
TI  - CHF project aims to bridge gap between providers.

PMID- 16422436
TI  - Improvements don't end with the action plan.

PMID- 16422437
TI  - 'Culture of safety' yields dramatic results.

PMID- 16422438
TI  - CPOE: It's not a ... say the experts, so the time to prepare is now.
AB  - The implementation of Computerized Physician Order Entry can be challenging and
      complicated, but you can make the process much smoother with careful planning.
      Staff up before going live. The first several weeks will slow down the
      department. Have enough computers for all staff, including residents and
      attendings. Take a "go-slow" attitude when it comes to installing medication
      allergy alarms.

PMID- 16422440
TI  - To cut diversions, get other units involved.
AB  - Integrate your own internal solutions for reducing diversions with process
      improvements developed in concert with other departments. This approached helped
      one ED reduce diversions by 72%, reduce length of stay from 397 to 372 minutes,
      and increase patient satisfaction from 3.96 to 4.11 on a five-point scale. Show
      radiology, lab, inpatient staff how unavailable beds or slow test result times
      can cause a patient logjam in the ED. Seek opportunities to move testing done in
      other departments directly into the ED. Give your nurses the authority to order
      certain treatment on their own.

PMID- 16422439
TI  - Atypical patient profiles common after disasters.
AB  - Follow the "surge, sort, support" triage model to ensure a higher quality of care
      for victims of communitywide disasters. Alert your staff that up to 80% of your
      patients will be self-referred. A large number of patients will have unexplained
      physical symptoms. Have a separate space available to function as a support
      center.

PMID- 16422441
TI  - Tiered structure helps ED improve flow, satisfaction.
AB  - Subdividing the major management tasks of one ED lightened the manager's load and
      gave staff a clearer idea of where to take their problems, helping to drop
      average length of stay from 85 minutes to 45 minutes, reduce throughput from 308
      minutes to 230 minutes, and improve patient satisfaction from 74.6% to 84%. Where
      possible, divide responsibilities according to the talents of the individual
      nurse managers. A manager with ED and observation unit responsibilities improves
      communication between the units. Tiered staffing structure creates ready-made
      "team leaders" for departmentwide initiatives.

PMID- 16422442
TI  - 2-pronged approach improves pain recording.
AB  - Take a proactive approach towards staff education and charting procedures to
      improve staff performance in documenting pain in children. Hold regular
      inservices on an individual or small-group basis. Review importance of pain
      documentation and most common meds used. Make sure that physicians, as well as
      nurses, are encouraged to document pain in the medical record. Adjust your chart
      design so that commonly overlooked areas are more likely to catch the eye of
      staff members.

PMID- 16422443
TI  - Inpatients in the ED: caught between two worlds.

PMID- 16422444
TI  - Pelvic trauma.

PMID- 16422445
TI  - The Tapered Groovy implant optimizes implant success in suboptimal clinical
      conditions.

PMID- 16422446
TI  - Stroboscopic vision as a treatment for motion sickness: strobe lighting vs.
      shutter glasses.
AB  - INTRODUCTION: Countermeasures (e.g., drugs, training, etc.) designed to combat
      the problem of space motion sickness (SMS) have had only limited successes. A
      possible solution for SMS and terrestrial motion sickness may rest in preventing
      retinal slip via stroboscopic vision. METHODS: There were 32 subjects who
      participated in a study to investigate the effect of stroboscopic illumination on
      motion sickness using either a strobe light or liquid crystal display (LCD)
      shutter glasses. There were 19 subjects who read text and made +/- 20 degrees
      head movements in the horizontal plane (yaw) at 0.2 Hz while wearing left-right
      reversing prisms and exposed to 4-Hz stroboscopic or normal room illumination
      (control condition). Motion sickness was scored using the Miller and Graybiel
      scale and subjective self-ratings. In a crossover design, testing was repeated
      using stroboscopic LCD shutter glasses with an additional 13 subjects and 6
      subjects from the first condition. RESULTS: During the experiment with a strobe
      light, motion sickness scores were significantly lower than in the control
      condition (chi 0.32 strobe vs. chi 3.79 light = p < 0.003). Results with the LCD
      shutter glasses corresponded with those when the environment was strobed in an
      otherwise dark room (chi 1.0 glasses vs. chi 4.1 light = p < 0.001). CONCLUSIONS:
      Stroboscopic illumination reduced the severity of motion sickness symptoms, and
      shutter glasses with a flash frequency of 4 Hz are as effective as a strobe
      light. Stroboscopic illumination appears to be an effective countermeasure where
      retinal slip is a significant factor in eliciting motion sickness due to either
      self- or surround-motion.

PMID- 16422447
TI  - Decompression sickness in a swine model: isobaric denitrogenation and
      perfluorocarbon at depth.
AB  - INTRODUCTION: Disabled submarine survivors could achieve inert gas tissue
      saturation likely to cause severe decompression sickness (DCS) on surfacing. This
      risk increases with time and depth of exposure. Methods to reduce DCS risk and
      severity are needed specifically for such an operational scenario. METHODS:
      Yorkshire swine (16.2-26.6 kg) fitted with an external jugular catheter were
      compressed to 5 ATA for 22 h. They then received an enriched breathing mix of 44%
      N2 and 56% O2, and an infusion of either saline or a perfluorocarbon (PFC)
      emulsion, and were observed for 2 h before surfacing without decompression stops.
      Controls were surfaced after 22 h saturation at 5 ATA. Surface observations
      continued for another 2 h on all animals and signs of DCS were recorded to the
      nearest minute. RESULTS: Seizure activity at depth was noted in 0/26 controls,
      1/16 in the saline group, and 7/16 in the PFC group. DCS in < 2 h occurred in
      25/26 air controls, 2/15 in the enriched mix/saline group, and 4/9 not suffering
      seizure in the enriched mix/PFC group. Death in < 2 h occurred in 23/26 controls,
      1/15 in the saline group, and 1/9 in the PFC group. DISCUSSION/CONCLUSION: This
      study demonstrates the benefits of breathing increased O2 at depth prior to rapid
      decompression and the deleterious effects of PFC administration at depth in a
      swine saturation model with rapid decompression. Future studies should examine a
      minimal O2 pre-breathe period to offer protection against DCS as well as the role
      of PFC use after surfacing.

PMID- 16422448
TI  - Decompression schedule optimization with an isoprobabilistic risk of
      decompression sickness.
AB  - INTRODUCTION: Divers use decompression schedules to reduce the probability of
      occurrence of decompression sickness when returning to the surface at the end of
      a dive. The probability of decompression sickness resulting from these schedules
      varies across different dives and the models used to generate them. Usually the
      diver is unaware of this variance in risk. This paper describes an investigation
      into the feasibility of producing optimized iso-probabilistic decompression
      schedules that minimize the time it takes for a diver to reach the surface.
      METHODS: The decompression schedules were optimized using the sequential
      quadratic programming method (SQP), which minimizes the ascent time for a given
      probability of decompression sickness. The U.S. linear-exponential multi-gas
      model was used to calculate an estimate of the probability of decompression
      sickness for a given dive. In particular 1.3-bar oxygen in helium rebreather
      bounce dives to between 18 m and 81 m were considered and compared against the UK
      Navy QinetiQ 90 tables for a similar estimate of probability of decompression
      sickness. RESULTS: The SQP method reliably produced schedules with fast and
      stable convergence to an optimized solution. Comparison of the optimized
      decompression schedules with the QinetiQ 90 schedules showed similar stop times
      for shallow dives to 18 m. For dives with a maximum depth of 39 m to 81 m,
      optimizing the decompression resulted in savings in decompression time of up to
      30 min. CONCLUSIONS: This paper has shown that it is feasible to produce
      optimized iso-probabilistic decompression tables given a reliable risk model for
      decompression sickness and appropriate dive trials.

PMID- 16422450
TI  - Speech intelligibility in noise using throat and acoustic microphones.
AB  - INTRODUCTION: Helicopter cockpits are very noisy and this noise must be reduced
      for effective communication. The standard U.S. Army aviation helmet is equipped
      with a noise-canceling acoustic microphone, but some ambient noise still is
      transmitted. Throat microphones are not sensitive to air molecule vibrations and
      thus, transmittal of ambient noise is reduced. It is possible that throat
      microphones could enhance speech communication in helicopters, but speech
      intelligibility with the devices must first be assessed. In the current study,
      speech intelligibility of signals generated by an acoustic microphone, a throat
      microphone, and by the combined output of the two microphones was assessed using
      the Modified Rhyme Test (MRT). METHODS: Stimulus words were recorded in a
      reverberant chamber with ambient broadband noise intensity at 90 and 106 dBA.
      Listeners completed the MRT task in the same settings, thus simulating the
      typical environment of a rotary-wing aircraft. RESULTS: Results show that speech
      intelligibility is significantly worse for the throat microphone (average percent
      correct = 55.97) than for the acoustic microphone (average percent correct =
      69.70), particularly for the higher noise level. In addition, no benefit is
      gained by simultaneously using both microphones. A follow-up experiment evaluated
      different consonants using the Diagnostic Rhyme Test and replicated the MRT
      results. DISCUSSION: The current results show that intelligibility using throat
      microphones is poorer than with the use of boom microphones in noisy and in quiet
      environments. Therefore, throat microphones are not recommended for use in any
      situation where fast and accurate speech intelligibility is essential.

PMID- 16422449
TI  - Trampoline exercise vs. strength training to reduce neck strain in fighter
      pilots.
AB  - INTRODUCTION: Fighter pilots' muscular strength and endurance are subjected to
      very high demands. Pilots' fatigued muscles are at higher risk for injuries. The
      purpose of this study was to compare the effects of two different training
      methods in reducing muscular loading during in-flight and cervical loading
      testing (CLT). METHODS: There were 16 volunteer Finnish Air Force cadets who were
      divided into 2 groups: a strength training group (STG) and a trampoline training
      group (TTG). During the 6-wk training period, the STG performed dynamic flexion
      and extension and isometric rotation exercises, and the TTG performed trampoline
      bouncing exercises. During in-flight and CLT, muscle strain from the
      sternocleidomastoid, cervical erector spinae, trapezius, and thoracic erector
      spinae muscles was recorded with EMG. RESULTS: In-flight muscle strain in the STG
      after the training period decreased in the sternocleidomastoid 50%, cervical
      erector spinae 3%, trapezius 4%, and thoracic erector spinae 8%. In the TTG, the
      decrease was 41%, 30%, 20%, and 6%, respectively. In CLT, the results were
      similar. After a 3-mo follow-up period with intensive high +Gz flying, EMG during
      CLT was still lower than in baseline measurements. CONCLUSION: Both training
      methods were found to be effective in reducing muscle strain during in-flight and
      CLT, especially in the cervical muscles. There was no statistically significant
      difference between the training groups. Introduced exercises expand muscles'
      capacities in different ways and the authors recommend both strength and
      trampoline training programs to be included in fighter pilots' physical education
      programs.

PMID- 16422451
TI  - Seat vibration in military propeller aircraft: characterization, exposure
      assessment, and mitigation.
AB  - INTRODUCTION: There have been increasing reports of annoyance, fatigue, and even
      neck and back pain during prolonged operation of military propeller aircraft,
      where persistent multi-axis vibration occurs at higher frequencies beyond human
      whole-body resonance. This paper characterizes and assesses the higher frequency
      vibration transmitted to the occupants onboard these aircraft. METHODS: Multi
      axis accelerations were measured at the occupied seating surfaces onboard the
      WC/C-130J, C-130H3, and E-2C Hawkeye. The effects of the vibration were assessed
      in accordance with current international guidelines (ISO 2631-1:1997). The
      relative psychophysical effects of the frequency components and the effects of
      selected mitigation strategies were also investigated. RESULTS: The accelerations
      associated with the blade passage frequency measured on the passenger seat pans
      located on the side of the fuselage near the propeller plane of the C-130J (102
      Hz) and C-130H3 (68 Hz) were noteworthy (5.19 +/- 1.72 ms(-2) rms and 7.65 +/-
      0.71 ms(-2) rms, respectively, in the lateral direction of the aircraft). The
      psychophysical results indicated that the higher frequency component would
      dominate the side passengers' perception of the vibration. Balancing the props
      significantly reduced the lower frequency propeller rotation vibration (17 Hz),
      but had little effect on the blade passage frequency vibration. CONCLUSIONS: The
      relationships among the frequency, vibration direction, and seat measurement
      sites were complex, challenging the development of seating systems and mitigation
      strategies. Psychophysical metrics could provide a tool for optimizing mitigation
      strategies, but the current international vibration standard may not provide
      optimum assessment methods for evaluating higher frequency operational exposures.

PMID- 16422452
TI  - Crew familiarity: operational experience, non-technical performance, and error
      management.
AB  - INTRODUCTION: Crew familiarity, in terms of having recent operational experience
      together as a crew, is seen as an important safety-related variable. However,
      little evidence exists to unpack the underlying processes with respect to
      familiarity. This study investigated the relationships between crew familiarity,
      non-technical performance, and error management. METHOD: Data were collected
      during normal line operations at a commercial airline by observers using a
      methodology based on the Line Operations Safety Audit (LOSA). A total of 154
      flights were analyzed, 31% of which were operated by an unfamiliar crew, with 69%
      operated by a familiar crew. RESULTS: The rate of error occurrence was found to
      be higher for unfamiliar crews, and these crews were found to make different
      types of errors when compared with familiar crews. However, with respect to the
      management of error events, no significant difference was found between
      unfamiliar and familiar crews. No significant effect of crew familiarity was
      found with respect to crews' non-technical performance. However, strong
      correlations were found between crews' non-technical performance and the
      management of errors. DISCUSSION: The findings indicate that crew familiarity, in
      terms of whether a crew has flown together recently or not, has little
      operational significance with respect to the management of error events during
      normal line operations. Accordingly, the suggestion that unfamiliar crews operate
      at a higher level of safety-related risk was not supported. Non-technical
      performance appears to be a stronger driver of effective error management than
      crew familiarity, and is highlighted as a focus for further investigation and
      intervention.

PMID- 16422453
TI  - Aviation signal light gun: variations in photometric and colorimetric properties
      among airports.
AB  - PURPOSE: The aviation signal light gun (LG) is believed by some to be the only
      color-critical task in aviation without redundant coding. However, there are
      questions regarding its practicality as a test of color vision given that the
      brightness and colors may vary between airports. METHODS: The chromaticity
      coordinates and relative intensities of five LGs were measured with a portable
      spectroradiometer. Four of the LGs were measured at airports in southern Ontario
      and compared with a newly purchased LG (ATI Avionics). The air traffic
      controllers (ATCs) were also surveyed regarding the frequency of LG use. RESULTS:
      Only 40% of the LGs at the airports were in good working condition. All working
      LGs met the ICAO standards for airport signal lights. However, differences did
      exist between models which were related to the date of manufacture. Older LG
      lights were dimmer and their green and white lights were more yellow than the
      newer LGs. ATCs reported that they used the LG primarily for pilot instruction
      and demonstration. However, in two locations, the LG was used to signal pilots
      who were flying their aircraft in for radio repair. This occurred about once or
      twice a month. DISCUSSION: The LG is used primarily for instructional purposes.
      However, if a radio repair shop is at the airport, then the LG will be used about
      once to twice a month. There is sufficient variability in the light colors and
      intensity across airports so that any given LG cannot be used as valid practical
      test of color vision in aviation.

PMID- 16422454
TI  - Hearing thresholds for U.S. Marines: comparison of aviation, combat arms, and
      other personnel.
AB  - INTRODUCTION: Aviation personnel in the U.S. Marine Corps are exposed to auditory
      trauma that may produce hearing loss in excess of personnel with other work
      exposures. METHODS: U.S. Marine Corps personnel in the Navy and Marine Corps
      Hearing Conservation Database (1995-1999; n = 20,645) were analyzed. The outcome
      variable was a hearing threshold at 4000 Hz in the left ear greater than 25 dB
      for annual and periodic audiograms. Personnel were characterized by gender,
      officer status, 5-yr age groups, and by military occupational skills (MOS) groups
      of "aviation," "combat arms," and "other." RESULTS: After adjustment by logistic
      regression for age group, gender, and officer status, the "aviation" group was
      not different from the "other" category, while the "combat arms" group was more
      likely to have elevated hearing thresholds. Officers and women demonstrated
      significantly lower rates for elevated thresholds. DISCUSSION: These findings
      provide information for personnel planning and assessing military hearing
      conservation programs.

PMID- 16422455
TI  - Hearing in military pilots: one-time audiometry in pilots of fighters,
      transports, and helicopters.
AB  - INTRODUCTION: Pilots are exposed to potentially harmful levels of noise, the
      actual consequences of which are still poorly documented. We have determined the
      audiometric profiles of pilots as a function of age and type of aircraft (i.e.,
      fighter, transport, helicopter) and have searched for risk factors of deafness
      other than noise in a pilot population. METHODS: We examined 521 French military
      pilots ages 20-40 yr during their annual medical check-ups. Pilots were
      interviewed using a standardized questionnaire and data from tonal audiograms of
      both ears were collected. Hearing levels were compared between groups of age and
      aircraft category. RESULTS: Abnormal hearing levels in pilots were found
      essentially at high frequencies with a marked notch on audiograms at 6 kHz. Left
      ears had a significantly poorer performance compared with right ears. At a given
      age, transport pilots had, on average, better hearing at 8 kHz than other pilots,
      despite a higher number of flying hours. In addition to the 6 kHz notch,
      helicopter pilots showed a significant hearing loss at 3 kHz. Such an enlargement
      of the impaired frequency range can disturb speech communication. Prevalence of
      otitis media in childhood was significantly higher in pilots with abnormal
      hearing. DISCUSSION: Pilots flying fighter and helicopter aircraft are at a
      higher risk of hearing loss compared with pilots flying transport aircraft.
      Improvements in ear protection seem particularly needed for the left ear. Hearing
      losses can potentially compromise speech communication in helicopter pilots.

PMID- 16422456
TI  - Ejection decisions by strike pilots: an extreme value interpretation.
AB  - BACKGROUND: An explanation is offered for the asymmetry of Receiver Operating
      Characteristic (ROC) curves obtained from pilots' decisions to eject. The curves
      can be fitted by a Gaussian model with unequal variances; however, that model
      does not provide a ready interpretation of the shape of the obtained ROCs.
      HYPOTHESIS: In an emergency, a pilot receives information from many parallel
      sources and will decide to eject if any one value from these sources exceeds the
      criterion for ejection. This process can be described by the extreme maximum
      value model. RESULTS: When fitted to published asymmetrical ROC curves for the
      decision to eject, the extreme maximum value model with one parameter provides a
      better fit, according to Akaike and Baysean information criteria, than the
      unequal variance Gaussian model with two parameters. DISCUSSION: In an emergency
      a pilot's decision to eject depends on whether any one value from several sources
      provides sufficiently strong evidence to exceed the criterion for ejection. A
      decision based on this policy is described by the extreme value model, which,
      therefore, offers a credible explanation of why the obtained ROCs are
      asymmetrical in shape.

PMID- 16422457
TI  - Vocal cord paralysis in a fighter pilot.
AB  - We present in this case report the return to flying duty of a pilot with vocal
      cord paralysis secondary to removal of a thymoma. We discuss the importance of
      glottic function as it pertains to the unique aviation environment. We also
      discuss the anatomy and physiology of the glottis, the evaluation for vocal cord
      paralysis, and surgical approaches for paralyzed vocal cords. Although the
      incidence of recurrent laryngeal nerve paralysis is low in the military aviation
      community, it is important to recognize that its sequelae can be managed so that
      the aviator may return to flight duties.

PMID- 16422458
TI  - Essential thrombocytosis and myocardial infarction in an aircrew member:
      aeromedical concerns.
AB  - Of essential thrombocytosis (ET) cases, 25% occur in patients younger than 40 yr
      of age, and are often discovered as an incidental laboratory abnormality.
      However, the risk for thrombosis remains of concern and needs to be closely
      evaluated, especially in the aerospace environment. We report on the case of a 40
      yr-old, female French military air traffic controller (ATC) admitted for an ST
      elevation myocardial infarction. She was a smoker and had no previous medical
      history of ET. The coronary angiogram showed a thrombus of the left anterior
      descending coronary artery. She was treated medically with angioplasty and stent.
      Laboratory data revealed an elevated platelet count (495,000 x mm(-3)), confirmed
      6 mo later (645,000 x mm(-3)). The diagnosis of ET was then established. No
      platelet-lowering therapy was prescribed, aspirin was continued, and this ATC was
      considered unfit for operational duties. Arterial thrombosis is more frequent
      than venous in ET, and can affect the whole arterial tree from the microscopic to
      the main arteries. Thrombosis is unpredictable and, due to abnormalities of the
      platelet functions and associated cardiovascular risk cofactors, may occur even
      with an almost normal platelet count. Risk-adjusted therapy is needed, including
      lifestyle modification to address vascular risk factors, antiplatelet drugs
      (aspirin), and platelet-lowering agents with their risk of leukomutagenesis.
      Furthermore, there is no consensus for the prevention of venous thrombosis. The
      decision for the aeromedical expert is difficult and depends on the specialty of
      the aircrew member, the type and duration of the mission, the therapeutics used,
      and the benefit-risk ratio of platelet-lowering agents.

PMID- 16422460
TI  - Multi-sensor integration systems for the tactical combat pilot.

PMID- 16422459
TI  - Aeromedical evacuation in the "Luftwaffe" from its origins until 1945.
AB  - Prior to WWII, Germany had little experience in aeromedical evacuation (AE) of
      the sick and wounded. The need for a specialized AE organization was recognized,
      organized, and used extensively on all fronts during WWII. Nearly 2.5 million
      casualties were transported by regular troop carriers and 11 specialized AE
      Units, which concentrated on the intensive care air transport of the seriously
      wounded, especially those with injuries of the brain, eyes, or jaw, thoracic or
      abdominal wounds, or gun-shot fractures. The AE Units were commanded by medical
      officers, most of whom were pilot-physicians, who had command jurisdiction over
      flying and line personnel as well as medical service personnel. The AE Units were
      equipped with both Junkers Ju-52s, which could carry up to 12 litter patients
      plus 3 to 5 ambulatory patients each, and with Fieseler Fi -156s (STOL "Stork"
      for 1 or 2 litter patients), ambulances, as well as the personnel needed for
      operating and maintaining the vehicles and materiel. The AE Units of the
      Luftwaffe--the Sanitaetsflugbereitschaften--made an outstanding contribution to
      military medical care in achieving this significant number of casualties
      evacuated under the humanitarian symbol of the Red Cross.

PMID- 16422461
TI  - This month in aerospace medicine history--January 2006.

PMID- 16422462
TI  - Demodex mites as a cause of human disease.

PMID- 16422463
TI  - What's eating you? The South African fattail scorpion (Parabuthus transvaalicus).

PMID- 16422464
TI  - What is your diagnosis? Lymphangioma circumscriptum (benign lymphangiectasia).

PMID- 16422465
TI  - Enhancing the care and treatment of skin of color, part 2: understanding skin
      physiology.
AB  - Cutaneous diseases in patients with skin of color frequently present differently
      than in individuals with white skin. Increased understanding of skin physiology
      including skin lipids and barrier function, as well as documentation of common
      issues such as ashy skin, has been the focus of researchers. New insights into
      the effects of UV radiation in skin of color and the increasing incidence of
      malignant melanoma heighten awareness of the need for new initiatives directed at
      education and further research, despite previous views about photoprotection for
      this population.

PMID- 16422466
TI  - Angiosarcoma: a case report and review of the literature.
AB  - Angiosarcoma is an aggressive neoplasm that predominantly affects elderly
      patients. Most cases appear on the scalp and face de novo; however, trauma,
      longstanding lymphedema, and irradiation are predisposing factors. Management
      includes a multidisciplinary team and may involve a combination of surgery,
      radiation, and chemotherapy tailored to the patient's age and associated
      comorbidities.

PMID- 16422467
TI  - Resistant scalp folliculitis secondary to Demodex infestation.
AB  - Folliculitis is a common complaint and its etiology may be related to a variety
      of factors. We examine a case involving a 57-year-old white man presenting with
      scalp erythema and folliculitis secondary to Demodex mite infestation. We discuss
      the pathophysiology of Demodex folliculitis, as well as the epidemiology,
      clinical manifestation, diagnosis, and treatment of this infection.

PMID- 16422468
TI  - The disappearing nail bed: a possible outcome of onycholysis.
AB  - Onycholysis is a separation of the nail plate from the underlying and/or lateral
      supporting structures (hyponychium, nail bed, lateral nail folds). It is a
      commonly seen disorder that is usually asymptomatic. We have observed a number of
      cases of onycholysis in which the distal nail bed appeared to shrink. The nail
      bed becomes keratinized and produces dermatoglyphics like the normal tip of a
      digit. This may explain why it is difficult to promote reattachment. If
      onycholysis persists, the condition is more likely to become irreversible and
      form the "disappearing nail bed." The best chance of resolving onycholysis is to
      try to identify the causative agent and institute early therapy.

PMID- 16422469
TI  - Large, nonhealing scalp ulcer associated with scarring alopecia and
      sclerodermatous change in a patient with porphyria cutanea tarda.
AB  - Porphyria cutanea tarda (PCT) is a disorder caused by deficient activity of a
      liver enzyme that leads to the accumulation of photoactive metabolites in the
      skin. The initial clinical presentation commonly includes mechanical fragility of
      the skin and blisters in sun-exposed areas. Sclerodermatous skin changes and
      scarring alopecia are described in up to 20% of patients. Although these unique
      skin changes have been reported in the literature, information regarding
      nonhealing ulcers of extraordinary size is lacking. We report a unique cutaneous
      manifestation of PCT that is not well documented: unusually large, nonhealing
      ulcers in the setting of sclerodermatous skin changes and scarring alopecia.

PMID- 16422470
TI  - The vanishing biopsy: the trend toward smaller specimens.
AB  - Dermatopathologists have noted an increased number of smaller biopsy specimens.
      Our objective was to determine whether dermatologists are changing their choice
      of biopsy technique and the size of biopsy specimens. We conducted a
      retrospective study of 500 biopsies performed by dermatologists for the purpose
      of diagnosis in 1988, 1993, 1998, and 2003. Our study results indicate that
      dermatologists are performing fewer punch biopsies and more shave biopsies.
      What's more, there has been a decrease in the size of shave biopsy specimens. We
      believe that the decreased number of punch biopsies being performed combined with
      the decreased size of shave biopsy specimens may affect patient care.

PMID- 16422471
TI  - Conventional CT and cone beam CT for improved dental diagnostics and implant
      planning.

PMID- 16422472
TI  - [Our outpatient cases for home anti-cancer chemotherapy].
AB  - We report our outpatient cases for home anti cancer chemotherapy. A total of 97
      patients with advanced and recurrent cancer (22 with breast, 20 gastric, 29
      colonic, 12 rectal, 1 hepatic, 3 cholangio, 4 pancreatic, 2 duodenal, 2 ovarian
      and 2 malignant lymphomas) were performed at an outpatient clinic or provided
      home anti-cancer chemotherapy since December 1996. Of these patients, 9 patients
      were provided home anti-cancer chemotherapy, 56 patients had died, and 41
      patients are alive and undergoing continuous therapy. The response rates revealed
      effective results in these diseases. No severe side effects were seen, and they
      underwent treatment at an outpatient clinic easily. The treatment of outpatients
      for home anti-cancer chemotherapy was effective and maintained the patient's QOL.
      However, it was important to establish early an exclusive therapy room, training
      of expert nurses and good staff.

PMID- 16422473
TI  - [Current status and problems in the chemotherapy of our outpatient clinic in the
      department of clinical oncology].
AB  - The department of clinical oncology performed an analysis of the current
      situation and problems inherent to 4500 chemotherapies of the outpatient clinic
      for the last 20 months using a new department of the outpatient clinical
      treatment. Divided into primary organs and the application of chemotherapy are as
      follow: breast cancer 49%, and gastrointestinal cancer 47% (esophageal cancer 4%,
      stomach cancer 28%, colorectal cancer 15%) and others 4%. In terms of time
      consumed by chemotherapy, there were differences in the tumors, regimens and
      ages. Within one hour, 40% of all chemotherapies mainly included those of breast
      cancers. From one to two hours, 40% included half breast cancers and half gastro
      intestinal cancers, two to three hours, 15% the same as one to two hours. Over 3
      hours, 5% mainly include those of gastro-intestinal cancers. In outpatient
      clinical chemotherapy, there were no human errors such as the use of wrong drugs
      and wrong intravenous injections. There were a few patients with adverse effects
      of chemotherapy including high fever with bone marrow suppression and severe
      diarrhea, who had an emergency admission to the hospital. As we perform an
      outpatient clinical chemotherapy with safe, it is important to coordinate with
      family doctors. To decrease the patients' effort of outpatient clinic, we request
      the treatment of high fever and the dose of G-CSF for bone marrow suppression to
      family doctors. The outpatient clinical chemotherapy enables to offer the
      suitable tailor-made treatment for each individual and to control the adverse
      effects of any regimen. But, patients' waiting period is still longer due to lack
      of numbers of doctors. To improve these statuses, careful consideration will be
      required for the trusting relationship with paramedical staffs' in the Department
      of Clinical Oncology.

PMID- 16422474
TI  - [Management of cancer chemotherapy for outpatients--effectiveness of using cancer
      chemotherapy protocol database for outpatients].
AB  - The present study investigated that a cancer chemotherapy protocol registration
      system was a safe management of cancer chemotherapy for outpatients. A protocol
      database was made with a personal computer and 122 protocols for 15 diseases were
      registered until the end of April 2005. As a result, it was easy to check
      injection prescriptions. Sixty-one errors including 13 dosage errors for 2409
      prescriptions were corrected. The time to check prescriptions were shortened,
      preparation and dosage mistakes were prevented, and stocking drug decreased by
      dissolution liquids being made with a standardization of using the same bottle
      (the cost of stocking drug: 40,418 yen). Therefore, the system and database are
      effective in raising safety of treatments and an increase in efficiency.

PMID- 16422475
TI  - [Present state and future of chemotherapy in out-patient clinic].
AB  - As the frequency of chemotherapy was increasing at an out-patient clinic,
      chemotherapy centers for an outpatient clinic have been established. When
      chemotherapy was carried out for 25 patients in a day at an outpatient clinic,
      the mean time was 27.6 minutes from ordering the drugs to the drugs' arrival.
      When the line was crowded, the drug arrival time was more than one hour, and at
      least 90 minutes was necessary to begin the chemotherapy. As the number of
      patients increases, it is necessary to have the effective use of a chemotherapy
      room and the patients have to be divided according to the duration of time
      required for chemotherapy. It appears that a continuation of infusion
      chemotherapy will be frequently carried out and the chemotherapy with an IVH port
      and a portable pump system will be popular in the future. It is necessary to make
      the system which supports a continuous infusion like this.

PMID- 16422476
TI  - [A terminal phase patient who can return home because of a multi-professional
      conference--considerations for multi-professional conference].
AB  - Palliative care has been provided in our sub-acute hospital ward and multi
      professional conferences have also taken place in order to enhance care. In this
      paper, we present a 72-year-old female who has suffered from relapse of lung
      cancer and was able to return home because of an execution of multi-professional
      conferences. We also present considerations that were carried out in multi
      professional conferences. We found some of the important factors for carrying an
      efficient conference are advance preparations in ahead, punctuality of the
      conference, a conference place that is kept in the ward, coping with nurse calls
      and participation of nutritionists. A timely conference, sharing information
      among the team and the education about a dying process are some of the future
      subjects.

PMID- 16422478
TI  - [Clinical pathway for long term home cares].
AB  - New tools of clinical pathway for long term home cares (care pathway) and new
      anamnesis charts on admission were introduced. These tools were based on
      Takeuchi's assessment methods. I describe that these tools make possible to
      develop collaborative works (team care) of co-medical staffs and promote a safe
      and rapid discharge from hospital.

PMID- 16422477
TI  - [A case report of a terminally ill patient who died of cancer at home under pain
      control].
AB  - Ninety percent of patients we handle at our visiting nurse group are last stage
      cancer patients. We report a terminally ill cancer patient who died at home under
      a high dose of powerful opioids to control pain. The patient was a 69-year-old
      woman with colorectal cancer. She lived together with her husband and their elder
      son's family. Even though the patient's condition dramatically shifted time to
      time, we could maintain a good QOL of the patient till her death at home. After
      the outpatient chemotherapy treatment began, we confirmed the patient's
      colorectal cancer had spread to her bones. We started using powerful opioids for
      pain control and the patient was eventually transferred to home hospice care.
      Then, the patient suffered a self destruction of the cutis metastasis layer and
      the disease caused broken bones on her left thigh. We however continued on
      providing home care service because of the patient's strong desire to stay home
      even if the family's concern as a care giver had multiplied. We increased the
      frequency of home visits and telephone calls in order to give medical and
      spiritual support for both the patient and her family. As a result, we could keep
      the patient's good QOL up to the time of her death. Based on the experiences
      through taking care of the patient, we strongly felt that the timing of proper
      guidance for the peaceful death to the family, a communication method or a
      communication system and telephone call visits were very important, in addition
      to controlling the condition of illness in order to keep up a good QOL for both
      the patient and her family.

PMID- 16422479
TI  - [Vasculitic condition following instillation of epirubicin hydrochloride in an
      outpatient chemotherapy].
AB  - The appearance of vasculitis is often observed following the use of epirubicin
      hydrochloride in outpatients. As it is important to continue to provide a safe
      treatment for outpatient with little or no side effects, the aim of this study
      was to reveal causes underlying the outbreak of vasculitis or the vasculitic
      state of patients who had undergone instillation of epirubicin hydrochloride as
      an adjuvant therapy following a breast cancer surgery. The study was conducted
      based on past investigation records. We extracted relevant factors such as age,
      previous illness, physical condition and dosage of epirubicin hydrochloride from
      past records which may all be connected to the outbreak of vasculitis. We
      administered one dose of epirubicin hydrochloride that was diluted into 50-100 ml
      of normal saline solution or 5% glucose and instilled over a period of 30
      minutes. As a result of this instillation of epirubicin hydrochloride, 35 out of
      45 cases displayed vasculitis. We did not observe any relationship among the aged
      (over 60), previous illness or physical condition (BMI over 25) and the
      appearance of vasculitis. When a dosage amount of more than 110 mg of epirubicin
      hydrochloride was administered, 23 out of 29 cases displayed vasculitis. From the
      past records, it was observed that the cause of vasculitis was dependent on the
      administrative method itself. As previous studies reported that vasculitis was
      low when epirubicin hydrochloride was retained in blood vessels for only a short
      time, our study, however, concentrated on how to administer epirubicin
      hydrochloride. Our results suggested that an adoption of a single dosage system
      may suppress the outbreak of vasculitis.

PMID- 16422480
TI  - [A contribution of a pharmaceutical department to the safety management of an
      outpatient's cancer chemotherapy].
AB  - A concern about safety management is growing rapidly in the field of an
      outpatient's cancer chemotherapy. Therefore, the pharmaceutical department of
      Tokai University Hachioji Hospital has employed; (1) a system to check injection
      prescriptions accompanied by records of drug administration and (2) an injection
      drug preparation worksheet for a certain communication. The results that examined
      their usability were as follows: (1) a prescription check found a deviation of
      recipes from the protocol, then all of the deviations were revised, (2) use of
      the worksheet with an indicated cancellation line completely prevented
      preparation mistakes in the case of a prescription change. Consequently, the
      safety management of an outpatient's cancer chemotherapy has made progress due to
      an application of the system and worksheet by the pharmaceutical department.

PMID- 16422481
TI  - [Aiming toward the supply of aseptic drugs--up to acceptance of the first
      patient].
AB  - As the ageing society has come, a categorized medical function has been advanced.
      Therefore, an improvement of medical care service for home care patients has been
      requested. One of the services provided by community pharmacists was to visit
      patient to give drug management advice based on the medical insurance and
      homecare insurance guidelines. In 1994, the Ministry of Health and Welfare
      expressed a degree of pharmacist's involvement to share patient's concern and was
      described as "the maturity of pharmacy". At present, the third step in the
      division of labor in medical services has taken its root. Then, an effort to
      arrange the fourth step (supply of aseptic drugs) will be needed in the future.
      Clinical exercises by pharmacists, acquisition of aseptic preparation skills and
      maintenance of facilities like a clean room will be required because the supply
      of aseptic drugs will be the first experience for a pharmacy. Neighboring medical
      facilities have to be prepared for accepting a supply of aseptic drugs along with
      the pharmacy's preparation. This time, we could have had an opportunity to accept
      the HPN patient. So we would like to report our progress and challenge.

PMID- 16422482
TI  - [Challenge of pharmacies to support home medical care].
AB  - Recently, hospitals have started to actively shorten the number of hospital days
      (hospital-stay and commuting days) of patients, as a result promotion of a home
      medical care has been started on that basis. Home medical care requires a fully
      equipped system in regional areas in terms of medical practitioners, home care
      nurses and drug supplies. From the system's perspective, home care for cancer
      patients is continually being promoted, so a drug supply system needs to be
      urgently put in place. Pharmacists are not only filling prescriptions for drug
      injectables, but they are also contributing to a proper use of drugs by engaging
      in patient home visits, and providing information to medical practitioners and
      home-visit nurses. In order to further promote home care, there will be a need to
      fully equip pharmacies and train pharmacists so they gain a rich clinical
      experience.

PMID- 16422483
TI  - [Management of the system to allow the terminal cancer patients and their
      families to choose from in-hospital care, outpatient care and home care at
      Matsuyama Bethel hospital].
AB  - Hospice ward at Matsuyama Bethel Hospital opened in April 2000. The hospice care
      has been provided for inpatients and outpatients. We considered a system that
      should be established to allow patients and their families to choose from in
      hospital care, outpatient care and home care. The hospice consultation for
      outpatients opened in April 2004. The terminal cancer patients who are within 6
      months of remaining days were hospitalized to the hospice ward. After making the
      hospice consultation for outpatients, hospice care services have been provided
      for terminal cancer patients including those with more than 6 months of remaining
      days under the coordination of palliative care for outpatients and inpatients.

PMID- 16422484
TI  - [Ways to make cooperation between hospital nurse and home visiting nurse in
      treating a final stage cancer patient at home].
AB  - Due to a payment system based on Comprehensive Medical Evaluation has been
      adopted, both a shorter hospitalization and the use of home nursing care have
      been increasing. A good cooperation between hospital and home visiting nurses is
      desired in order to transfer continued nursing. Regarding a home nursing care
      service for the most terminal cancer patients, we conducted a survey of 459 home
      visiting nurses with twelve questions in five categories: (1) Before transferring
      to home care, (2) Right after the transfer to home care, (3) Patient in a stable
      period, (4) Time of near death and (5) Other (Requests to hospital nurses). The
      following issues became clearer in terms of how hospital and home visiting nurses
      should be cooperating with the handling of last stage terminal cancer patients:
      (1) A home visiting nurse should have a coordinating role with a hospital nurse
      when the patient is discharged from the hospital. (2) A participation of home
      visiting nurses on the coordination guidance at the time of a patient discharge
      is influenced by a manpower of the nursing station. (3) Even though home visiting
      nurses found a discrepancy between the hospital information and what patients and
      their families were getting from the hospital, home visiting nurses have learned
      through the job to clarify what patient and family needs were, and they responded
      accordingly. (4) A coordination between hospital and home visiting nurses was
      needed quite often when the patient's time has come to die at home.

PMID- 16422485
TI  - [Questionnaire survey for doctors in the area of cooporation efforts when a
      terminal cancer is transformed to home medical care].
AB  - In order to smoothly transform a terminal cancer patient from hospital to home
      medical care, we surveyed based on questionnaires to examine doctor's roles of
      each primary and regional hospitals and its cooperation among the hospitals. We
      established two types of questionnaires for two groups, a primary doctor group
      and a regional doctor group, and distributed and collected them. A total of 123
      doctors (35 primary doctors and 88 regional doctors) responded out of 185
      doctors, and the collection rate was 66.5%. The survey result indicated that
      there were significant differences among the primary and regional doctors in
      evaluating patient's family members for understanding of the patients disease at
      the time of discharge, how to give a treatment to the patient, alleviating
      patient's disease conditions and a mental support given by doctor to family
      members from the hospital. Meanwhile, about 70% of regional doctors answered that
      family members had some sort of anxieties during a night and at the time of
      emergency to care the patient. It also revealed that about 70% of regional
      doctors had experienced troubles in coordinating with a primary hospital. On the
      other hand, 62% of primary doctors answered that they always provided necessary
      care to the patient at the time of emergency. In providing a safe and a high
      degree of QOL in home medical care settings, it is important to have specific
      common purposes among the two groups of doctors and patients. Furthermore, the
      primary and regional doctors have to be cooperative, specify duty roles when the
      patient is transformed to home medical care, and to have ways to accomplish
      mutual common goals for patients.

PMID- 16422486
TI  - [Utilization of the screening test for discharge support].
AB  - We hand out a list of screening tests for discharge support (the screening) to
      all patients upon admission, so that they can receive an early discharge.
      Implementing the screening as a balanced score card (BSC) evaluation index of the
      work performance by the nursing division, we were able to screen more than 40% of
      newly admitted patients immediately after the introduction of the screening. When
      more than two items of the screening questionnaire were checked, a discharge
      support intervention was introduced. Patients who checked items on the screening
      questionnaire have tended to request discharge support within a week of
      admission.

PMID- 16422487
TI  - [Experiences of family caregivers for patients suffering from dysphagia--the
      attempt of subjective caregiving].
AB  - The purpose of this study was to investigate the experiences of family caregivers
      for patients suffering from dysphagia following a stroke. This study, in
      particular, examines an approach for subjective caregiving. Eight primary
      caregivers for dysphagic patients, who receive homecare from visiting nurses,
      were interviewed in this research. A qualitative content analysis of semi
      structured interviews was used to analyze transcribed interview data. The overall
      experience of care is explained in seven phases. Phase 1: An initiation of caring
      for a dysphagic patient at home with a belief that it is possible to manage the
      care for patient, Phase 2: The sway of mind and acceptance of the reality of
      coming to terms with having to take care of a dysphagic patient, and then, to
      take a wise decision of doing so, Phase 3: A caregiver's inner struggle to
      provide foods even if patients cannot enjoy foods as before, and then, to take a
      wise decision of doing so, Phase 4: Coexistent feelings of "whether I can
      continue to give the care for the patient or I can't manage the care in the
      future", Phase 5: The feeling of caregiver, imaging that "if I were the
      caregiver, I would be able to take care of the patient," is obtained, Phase 6: An
      approach that aims at restructuring the life of the patient and Phase 7:
      Adjusting and balancing dysphagic patient's care and caregiver's personal life.
      An implication of this research includes the importance of assessing each
      caregiver's experiences. These findings may provide a direction for homecare
      nurses and other health professionals in targeting interventions that will meet
      the demand for caregivers.

PMID- 16422488
TI  - [Efficient use and problems associated with "home remote medical support system"-
      utilization of videophones for homecare patients].
AB  - "Home Remote Medical Support System" (the support system) is an interactive real
      time communication system, consisting of a vital health measuring device and a
      near-television quality home digital videophone installed at a residence, to
      connect a primary medical care institution and a homecare patient by information
      communication lines. Exclusive use of a telephone, vital health measuring device,
      TV monitor and camera are installed as home devices to communicate with a primary
      personal computer at the medical institution to manage patient's data and to have
      video phone health consultations. We employed and conducted the support system
      with a help from "the remote medical assistant task" operated by the local
      government since April 2004. Two patients actually used the support system in the
      first year although we initially planned to have three. In conclusion, the
      support system appears to have been useful for the health management of patients
      with stable conditions. Meanwhile, we have to reassess the application of the
      support system and to balance its accountability among the user efficiency, the
      content of the support provider and user expenses.

PMID- 16422489
TI  - [Examination of acute disease in the long-term geriatric ward].
AB  - We investigated the acute disorder in cases at the long-term geriatric ward.
      Fifty seven patients were admitted to the hospital during the period of October
      2002 to March 2005. In our study, the following items were analyzed: (1) the
      number of admission, (2) diagnosis, (3) the duration of hospital stay, and (4)
      the cause of death. The admission of respiratory disease patients, such as
      pneumonia, bronchitis and pleuritis, were most frequent and had the longest term
      of hospitalization. We also found that patients with respiratory disease had
      undergone percutaneous endoscopic gastrostomy (PEG), and their hospitalization
      was relatively shorter.

PMID- 16422490
TI  - [A home care adjustment help provided by a local medical support hospital--the
      role of home care adjusting full time nursing master].
AB  - The Tama Nanbu-Chiiki hospital is a community health support hospital in the
      sphere of the Minamitama insurance medical treatment that consists of five cities
      of the Minamitama district in Tokyo. The cancer medical treatment and emergency
      care are assumed to be an emphasis in medical treatment at the hospital, and an
      acute short-term hospital has 306 beds. The community health support hospital is
      organized with a general manager, clerical workers, a nursing master of MSW and
      nurses, and they execute cooperation with a community health organization. In the
      fiscal year 2004, we handled a total of 240 terminal patients. Of these, the HPN
      introduction guidance was conducted to 87 patients, and 34 of the 87 patients
      were transformed to being homecare treatment. Here, we report the role of a
      nursing consultation master based on the cases we handled at this hospital.
      Meanwhile, we also introduce a home care adjustment procedure to home IVH induced
      patients who require advanced medical treatments for home recuperation, when they
      discharged from the hospital.

PMID- 16422491
TI  - [A patient care experience of the psychologically impaired cancer patient against
      chemotherapy--the successful outpatient case report using a sedative agent to
      reduce vomiting].
AB  - We would like to present a case report on how we managed to reduce an adverse
      effect of chemotherapy, specifically vomiting and nausea with a sedative agent
      diazepam, when a patient was intravenously injected with chemotherapeutic agents
      at the outpatient department. The patient was a 39-year-old female who
      experienced total hysterectomy and bilateral oophorectomy due to ovarian ca.
      (stage III) on May 29, 2002. She used to have complained of severe vomiting
      whenever undergoing 4-day inpatient chemotherapies every month from June 2002 to
      April 2003. In the last chemotherapy, she suffered vomiting prior to a day before
      the infusion and after 5 days of the infusion. Because of her experience, the
      patient refused to undergo the following chemotherapy. Based on discussions with
      her, use of sedatives was chosen to relieve vomiting. Due to relief of stress,
      the patient slept and relaxed by means of a sedative effect during and after
      administration of chemotherapy. Since the reduction of vomiting, she has been
      accepting further chemotherapies.

PMID- 16422492
TI  - [Palliative home care of a breast cancer patient with esophageal metastasis after
      the operation of gastric fistula and tracheotomy--a case study].
AB  - A 66-year-old woman felt dysphagia gradually seven years after an operation of
      breast cancer. We diagnosed her with esophageal metastasis of the breast cancer,
      and carried out irradiation and outpatient chemotherapy. Because her general
      condition became worse after the treatment for about four years, we performed an
      operation of gastric fistula and tracheotomy to manage her nutrition and of an
      accidental swallowing. Although the patient and her family resisted a discharge
      from hospital due to the progressive nature of her illness and change in physical
      surroundings, she was eventually switched to take a homecare medical treatment
      with the support of a team care approach. The main purposes of the homecare
      treatment were to manage gastric fistula including the administration of anti
      cancer drugs, cervicobrachial pain control and tracheal cannula exchange. Though
      she was mentally stable and got along well with the family during the home stay,
      she was hospitalized again two months after the homecare treatment because of
      aggravated symptoms and the family's fatigue. We respected the value of her
      quality of life and gave careful considerations to support her during the entire
      period of re-hospitalization. She gently died two months after re
      hospitalization. We considered that this palliative home care could be realized
      with the palliative team care, nursing intervention visit and family support.

PMID- 16422493
TI  - [Population dynamics of endangered plant species Abies chensiensis].
AB  - In order to know the endangered status and causes of Abies chensiensis in Qinlin
      Mountains, a field investigation on 18 plots was conducted on its age structure,
      life table and fecundity, and its population dynamics were predicted by time
      sequence model. The analysis on the age structure of Abies chensiensis
      populations showed that there were fewer young individuals, but middle-aged and
      old individuals were relatively rich. The population D in Abies chensiensis
      Indigofera amblyantha-Carex lanceolata association showed a relatively stable
      development tendency, while other four populations (A, B, C and E) in Abies
      chensiensis-Pinus tabulaeformis-Sinarundinaria nitida-Carex lanceolata
      association, Abies chensiensis-Quercus aliena var. acutserrata-Litsea pungens
      Carex lanceolata association, Abies chensiensis-Betula albo-sinensis
      Sinarundinaria nitida-Duchesnea indica association, and Abies chensiensis-Pinus
      tabulaeformis-Smilax stans-Carex lanceolata association all showed an obviously
      declining tendency. The analysis on the life tables and survival curves showed
      that the survival curve of Abies chensiensis populations belonged to Deevey III,
      and the death peak of different populations was in the period of 60--100 years
      old. The number difference among populations reflected the population habitat.
      Time sequence prediction indicated the numbers of old individuals would be
      increased at the beginning, and decreased finally in 20, 40, and 80 years. It was
      difficult to maintain the population stability. Analysis on 10 ecological factors
      showed that tree coverage, soil organisms and air humidity influenced population
      positively, and human disturbance and sunlight influenced population negatively.
      In situ conservation should be taken as the most important management
      countermeasure, and natural regeneration should be promoted. At the same time,
      artificial population should be expanded.

PMID- 16422494
TI  - [Application of GIS and integrated mathematic models on estimating forest land
      wood productiveness and solar energy use efficiency].
AB  - Based on the meteorological elements observation and mountain soil survey in
      Fujian Province, this paper approached the application of geographic information
      system (GIS) and integrated mathematic models on estimating the grid wood
      productiveness and solar energy use efficiency (SEUE) of regional forest land.
      The results showed that there was a significant quadratic correlation of annual
      mean temperature, precipitation and total solar radiation energy(TSRE) with
      longitude, latitude and altitude, and their multiple correlation coefficients
      ranged from 0.692 to 0.981. The regional annual mean TSRE, temperature and
      precipitation could be well estimated by GIS and integrated models of quadratic
      tendency curve, and linear, quadratic and quartic inverse distance weighted
      interpolation. These annual means estimated by the models did not differ greatly
      from observed data, and the t test values were 1.29, 0.12 and 0.06, respectively.
      The grid wood productiveness and SEUE of regional forest land in Fujian could
      also be well estimated with the aid of GIS and integrated models, which ranged
      from 2.32 m3 x hm(-2) yr(-1) to 18.61 m3 x hm(-2) yr(-1) and from 0.11% to 0.91%,
      respectively.

PMID- 16422495
TI  - [Energy characteristics of Casuarina equisetifolia ecosystem on coastal sand in
      Dongshan County, Fujian Province].
AB  - The study on the energy characteristics of Casurina equisetifolia community on
      red earth eolian sandy soil and homogeneous eolian sandy soil in Dongshan County
      of Fujian Province showed that the standing biomass and energy of Casurina
      equisetifolia community were 15 681.84 g x m(-2) and 317 795.31 kJ x m(-2) on red
      earth eolian sandy soil, and 5 129.87 g x m(-2) and 10 575.50 kJ x m(-2) on
      homogeneous eolian sandy soil, respectively. On homogeneous eolian sandy soil,
      the gross caloric value of the community ranged from 19.98 kJ x g(-1) to 21.39 kJ
      x g(-1), of which, dead branch was the highest while root was the lowest, and its
      percentage was 46.93% (truck) > 16.44%(root) > 13.92% (branch) > 12.28% (dead
      branch) > 5.87% (bark) > 3.90% (leaf) > 0.66% (fruit). The return amount of
      litter was 2061.77 kJ x m(-2) x yr(-1), and the net energy productivity was
      12662.82 kJ x m(-2) x yr(-1). On red earth eolian sandy soil, the gross caloric
      value was 19.84 - 21.70 kJ x g(-1), among which, leaf was the highest while root
      was the lowest, and its percentage was 38.09% (truck) > 19.48% (branch) > 17.09%
      (root) > 16.86% (leaf) >6.83% (bark) > 0.88% (dead branch) > 0.77% (fruit). The
      returned amount of litter was 9070.47 kJ x m(-2) x yr(-1), and the net energy
      productivity was 31 298.70 kJ x m(-2) yr(-1). The standing biomass and energy of
      Casurina equisetifolia community were higher on red earth eolian sandy soil than
      on homogeneous eolian sandy soil, mainly because red earth eolian sandy soil had
      a thinner sandy layer (< 20 cm) and a stronger nutrient and water supplying
      ability.

PMID- 16422496
TI  - [Biomass and carbon storage of ground bryophytes under six types of young
      coniferous forest plantations].
AB  - This paper studied the biomass and carbon storage of the ground bryophytes under
      young Picea balfouriana (P), Pinus tabulaeformis (Y), Pinus armandii (H), Larix
      kaempferi (L), Picea balfouriana-Pinus tabulaeformis (P-Y), and Pinus
      tabulaeformis-Pinus armandii (Y-H) forest plantations in the upper reach of
      Minjiang River, Sichuan Province. The results showed that total biomass and
      carbon storage of ground bryophytes were relatively low, being 3.11 - 460.36 kg x
      hm(-2) and 1.12 +/- 0.03 x 168.95 +/- 0.92 kg x hm(-2), respectively. On plot
      level, only the bryophyte biomass between forest P and others, and the carbon
      storage between forest L and others were significantly different. The ground
      bryophyte had the highest biomass and carbon storage under forest P, while the
      lowest ones under forest H. Comprehensive analysis suggested that forest type and
      its structural feature might be the important factors determining the biomass and
      carbon storage of ground bryophytes, and thinning was an important measure to
      improve ground bryophyte growth and biomass production.

PMID- 16422497
TI  - [Chemical components of volatiles form withered black poplar leaves with
      different physiological age].
AB  - By the methods of steam distillation and GC-MS, this paper analyzed the chemical
      components of the volatiles from withered black poplar leaves. The main
      components of the volatiles from young leaves were(Z)-3-hexenol (44.81% ),4
      methyl-1-pentanol (21.85%) and 2-hydroxy-benzaldehyde (15.19%), those from
      matured leaves were(Z)-3-hexenol (28.71%) and 2-hydroxy-benzaldehyde (10.35%),
      while in the volatiles from senescent leaves, the main components were 2-hydroxy
      benzaldehyde (28.81%) and benzyl alcohol (15.06%). The (Z)-3-hexenol content in
      the volatiles was evidently decreased with increasing leaf age, while the species
      and contents of aromatic compounds were in adverse.

PMID- 16422499
TI  - [Characteristic study on village landscape patterns in Sichuan Basin hilly region
      based on high resolution IKONOS remote sensing].
AB  - To realize the landscape programming of agro-ecosystem management, landscape
      stratification can provide us the best understanding of landscape ecosystem at
      very detailed scales. For this purpose, the village landscapes in densely
      populated Jintang and Jianyang Counties of Sichuan Basin hilly region were mapped
      from high resolution (1 m) IKONOS satellite imagery by using a standardized 4
      level ecological landscape classification and mapping system in a regionally
      representative sample of five 500 x 500 m2 landscape quadrats (sample plots).
      Based on these maps, the spatial patterns were analyzed by landscape indicators,
      which demonstrated a large variety of landscape types or ecotopes across the
      village landscape of this region, with diversity indexes ranging from 1.08 to
      2.26 at different levels of the landscape classification system. The richness
      indices ranged from 42.2% to 58.6 %, except that for the landcover at 85 %. About
      12.5 % of the ecotopes were distributed in the same way in each landscape sample,
      and the remaining 87.5% were distributed differently. The landscape fragmentation
      indices varied from 2.93 to 4.27 across sample plots, and from 2.86 to 5.63
      across classification levels. The population density and the road and hamlet
      areas had strong linear correlations with some landscape indicators, and
      especially, the correlation coefficients of hamlet areas with fractal indexes and
      fragmental dimensions were 0.957* and 0.991**, respectively. The differences in
      most landscape pattern indices across sample plots and landscape classes were
      statistically significant, indicating that cross-scale mapping and classification
      of village landscapes could provide more detailed information on landscape
      patterns than those from a single level of classification.

PMID- 16422498
TI  - [Allelopathy and chemical constituents of Ligularia virgaurea volatile].
AB  - Ligularia virgaurea is a noxious weed widely distributed on the psychro
      grasslands of east Qinghai-Tibet Plateau of China, but the allelopathic effects
      of its volatile is less known. In this study, the allelopathy of L. virgaurea
      volatile to 5 kinds of grasses was examined, and its chemical constituents were
      analyzed by GC-MS. The results demonstrated that the volatile of growing L.
      virgaurea could inhibit the seed germination speed and germination rate of all
      tested grasses. The inhibitory effects on Elymus nutans and Bromus magnus were
      significant, while Poa annua and Festuca ovin were not very sensitive. 18 major
      constituents were identified from the essential oil of L. virgaurea, accounted
      for 68.24% of the total. The main chemical components were 2-methylheptane
      (9.84%), 3-methyl-heptane (8.25%), heptane (7.93%), 4-methyl-1-(methylethyl)
      bicyclo [3, 1, 0] hex-2-ene (7.79%), 3-methyl-hexane (6.38%), 2-methyl-hexane
      (5.54%), and D-limonene (4.70%). Monoterpenoids accounted for 16.58% of the
      total, indicating that volatilization was one of the ways by which L. virgaurea
      released allelochemicals. The allelopathy of the volatile may play an important
      role in enhancing the competitive ability of the species, and be one of reasons
      of grassland degeneration.

PMID- 16422500
TI  - [Heat island effect and human body comfortable degree in Zhengzhou city].
AB  - In this paper, the key factors of heat island effect in Zhengzhou city were
      monitored by grid method to study the diurnal and seasonal changes and the
      spatial distribution of the effect, and to evaluate the comfortable degree of
      human bodies at different sites of the city. The results showed that on the
      whole, the heat island effect had a unimodal diurnal change, while its intensity
      was distinctly different among seasons, being decreased in order of winter >
      spring > autumn > summer. The spatial distribution of heat island center was
      significantly related to its nearby industrial heat resources. As for the
      comfortable degree of human bodies, the People's Park was the best site because
      of its arbor virescence, while in the Xiliu Lake Park with lawn as its main
      greening type, its capability of improving microclimate was weaker. The railway
      station square still had 16% frequency of most comfortable degree, because of its
      open space and better air fluidity.

PMID- 16422502
TI  - [Water cycling characteristics of grassland and bare land soils on Loess
      Plateau].
AB  - The study under natural and simulated rainfall conditions showed that the
      variance coefficient of soil water in the grassland and bare land on Loess
      Plateau decreased with increasing soil depth, and the vertical change of soil
      water in drought year in the profile could be divided into four layers. In rainy
      year, the variance coefficient of soil water decreased first, increased later,
      and decreased lastly with the increase of soil depth, due to the continual
      rainfall infiltration and intensive evapotranspiration. The variance coefficient
      at surface soil layer was obviously smaller in rainy year than in drought year.
      Compared with that in bare land, the soil water cycling in grassland was deeper
      in depth and greater in intensity, as well as higher in evapotranspiration. The
      temporal change of soil water mostly depended on rainfall and evapotranspiration,
      especially in surface soil layer, and the change of soil water lagged behind
      gradually from low to deep layers in the profile. Soil water storage had a
      seasonal change, and could be divided into three main periods, i. e., decreasing
      in spring, alternatively decreasing and increasing in summer and autumn, and
      relatively stable in winter. In drought year, soil water storage decreased, and
      infiltrated rainfall was all consumed by intensive evapotranspiration. In rainy
      year, soil water storage increased, but most infiltrated rainfall (more than 80%)
      was consumed by intensive evapotranspiration.

PMID- 16422501
TI  - [Effects of land use type on soil nutrient distribution in northern agro-pasture
      ecotone].
AB  - Soil samples under five land use types were collected from Duolun County in the
      northern agro-pasture ecotone. Chemical analysis showed that soil nutrient
      content was the lowest in farmland, medium in grassland, and the highest in
      woodland, indicating that reclamation accelerated the decomposition of soil
      organic matter and the further loss of soil nutrients. To investigate the effects
      of land use type on soil organic matter, available phosphors, available nitrogen
      and total nitrogen, soils from four different land use types in the catchments
      with slopes steeper than 15 degrees were sampled and analyzed. Vertically, the
      content of soil nutrients from slope bottom to its top was two times higher in
      land use type cropland-grassland-woodland than in grassland-woodland-cropland.
      Such a difference indicated the positive effects of the former land use type on
      soil nutrient retention. Therefore, selecting this optimal land use type in
      studied area could improve local eco-environment and economic benefits.

PMID- 16422503
TI  - [Research on mineralization process of organic phosphorus in black soil in
      Northeast China].
AB  - Buried bag and incubation experiments were conducted to study mineralization
      process of organic phosphorus in black soil in Northeast China under different
      time sequences. The results showed that both the content and mineralized velocity
      of organic P decreased gradually as time went on, the cumulative mineralized rate
      increased step by step, whether it was used by the method of incubation or buried
      bag. Under incubation, two treatments' mineralized velocity reached the maximum
      at first month (31.67, 38.75 mg x kg(-1) x month(-1), respectively), and their
      cumulative mineralized rate and mineralized velocity at six months were 7.94%,
      13.26 mg x kg(-1) x month(-1) and 9.24%, 17.99 mg x kg(-1) x month(-1),
      respectively. Under buried bag, the mineralized velocity of five treatments all
      reached the maximum at first year (55.67, 55.65, 49.60, 19.71, 22.52 mg x kg(-1)
      month(-1), respectively), and the cumulative mineralized rate and mineralized
      velocity of maize root and wheat root treatments at three years both were
      approximately 50% and 35 mg x kg(-1) x month(-1), which were higher than those
      under soybean root andgrass root treatments. From two methods of studies on the
      mineralization process of organic P, it could be seen that the original content
      of organic P influenced its mineralized rate and mineralized velocity: the higher
      of the original content of organic P, the higher of its mineralized rate and
      mineralized velocity.

PMID- 16422504
TI  - [In vitro fermentation characteristics of crop straws and their combined
      utilization].
AB  - By the technique of in vitro gas production, this paper studied the in vitro
      fermentation characteristics of different kinds of crop straws and their combined
      utilization. The results showed that the theoretical maximum gas production and
      the gas production rate of silage corn were increased by 19.1% and 8.2%,
      respectively, compared to corn stalk. These two indices of mixed crop straws were
      higher than those of single crop straw, and significant positive interactions in
      gas production were observed after 48 h of incubation. It was concluded that a
      combined utilization of silage corn with different kinds of crop straws could be
      an efficient way to improve the nutritional characteristics. The optimum ratio of
      the mixture was 25/75 or 50/50 when silage corn mixed with wheat or rice straw.

PMID- 16422505
TI  - [Nutrient use efficiency and yield-increasing effect of single basal application
      of rice specific controlled release fertilizer].
AB  - A series of pot and field experiments and field demonstrations showed that in
      comparing with the commonly used specific-fertilizers containing same amounts of
      nutrients, single basal application of rice-specific controlled release
      fertilizer could increase the use efficiency of N and P by 12.2% - 22.7% and 7.0%
      - 35.0%, respectively in pot experiment, and the use efficiency of N by 17.1% in
      field experiment. In 167 field demonstrations successively conducted for 3 years
      in various rice production areas of Guangdong Province, single basal application
      of the fertilizer saved the application rate of N and P by 22.1% and 21.8%,
      respectively, and increased the yield by 8.2%, compared with normal split
      fertilization.

PMID- 16422506
TI  - [Soil C, N and P contents and their relationships with soil physical properties
      in wetlands of Dongting Lake floodplain].
AB  - Eight representative soil profiles were installed on three types of wetland (two
      profiles on Carex spp. -dominated floodplain, four on Phragmites-dominated
      floodplain, and two on paddy soil) in Dongting Lake floodplain of China in 2004,
      and their C, N and P contents, microbial biomass C, N and P, <0.001 mm clay
      particles, and bulk density were measured. The results indicated the spatial
      distribution of soil C and N and soil microbial biomass C, N, and P were very
      similar in the profiles (0-100 cm) of three types of wetland, being decreased
      gradually with depth, except for soil TP which was constant in the profiles. The
      percentages of soil microbial biomass C, N and P to soil organic C, total
      nitrogen and total phosphorus decreased gradually with depth. In top layer (0-10
      cm), the contents of soil organic C and microbial biomass C and the percentage of
      soil microbial biomass C to organic C were 19.63-50.20 g x kg(-1), 424.63 - 1
      597.36 mg kg(-1), and 3.17% - 4.82%, respectively, the contents of soil total N
      and microbial biomass N and the percentage of soil microbial biomass N to total N
      were 1.85-4.45 g x kg(-1), 57.90 - 259.47 mg x kg(-1), and 3.13% - 6.42%,
      respectively, and the content of soil microbial biomass P and the percentage of
      soil microbial biomass P to soil total P was 24.16 - 200.99 mg x kg(-1) and 1.09%
      - 11.20%, respectively. The bulk density of soil top layer (0 -10 cm) was 0.65 -
      1.04 g x cm(-3), and the content of < 0.001 mm clay particles was 26.24% -
      39.48%. The contents of soil organic C and N and microbial biomass N and P in 0 -
      10 cm layer were the highest in Carex spp.-dominated floodplain, followed by
      paddy soil, and Phragmites-dominated floodplain. Also in 0 - 10 cm layer, the
      soil microbial biomass C in Carex spp. dominated floodplain and paddy soil was
      higher than that in Phragmites-dominated floodplain, while the soil bulk density
      in Phragmites-dominated floodplain was higher than that in paddy soil, and much
      higher than that in Carex spp. -dominated floodplain. The amount of soil < 0.001
      mm clay particles in Carex spp. -dominated floodplain and Phragmites-dominated
      floodplain was higher than that in paddy soil. In these three types of wetland,
      soil organic C and N and microbial biomass C, N and P had a significant logarithm
      correlation (P < 0.01) with <0.001 mm clay particles, and a significant index
      correlation (P <0.01) with bulk density.

PMID- 16422507
TI  - [Effects of tillage method and herbicide on cornfield weed community].
AB  - By the method of community ecology, this paper surveyed the weed community in a
      cornfield at the Shenyang Experimental Station of Ecology, CAS, and studied the
      effects of tillage method and herbicide on the weed composition, species
      diversity, and biomass at the experimental site. The results showed that the
      dominant weed species in the cornfield were Eriochloa villosa, Abutilon
      theophrasti, Bidens frondosa and Commelina communis, of which, Eriochloa villosa
      had the highest important value. In non-tillage field without herbicide
      application, the weed community had larger biomass, higher richness (S) and
      concentration (C), but lower species diversity (D) and species evenness (J).
      Herbicide could decrease weed species and inhibit biomass growth significantly in
      non-tillage field. It was clear that tillage method and herbicide could affect
      the weed composition, diversity and stability significantly.

PMID- 16422508
TI  - [Effects of nitrogen supply on flag leaf photosynthesis and grain starch
      accumulation of wheat from its anthesis to maturity under drought or
      waterlogging].
AB  - In this paper, a cement pool culture experiment with three water treatments
      (waterlogging, drought, and moderate water supply) and two nitrogen levels (120
      and 240 kg x hm(-2)) was conducted to study the effects of nitrogen supply on the
      flag leaf photosynthesis and grain starch accumulation of two wheat varieties
      from anthesis to maturity under soil drought and waterlogging. In comparing with
      moderate water supply, soil drought and waterlogging reduced the photosynthesis
      rate (Pn) and SPAD of flag leaf and dry matter accumulation. Nitrogen supply
      under drought increased Pn and SPAD, while that under waterlogging was in
      adverse. The total soluble sugar content in grain was reduced under both drought
      and waterlogging, while that in leaf was decreased under waterlogging but
      increased under drought. Under waterlogging, increasing nitrogen application rate
      reduced starch accumulation. The unit grain weight and the yields of grain and
      starch were reduced under both drought and waterlogging, but nitrogen application
      favored them under drought while in adverse under waterlogging. It was indicated
      that both leaf photosynthesis and grain starch accumulation could be regulated by
      nitrogen supply under stress of soil drought or waterlogging from anthesis to
      maturity of wheat.

PMID- 16422509
TI  - [Genetic relationships among four Bactrocera Cucurbitae geographic populations in
      Yunan Province].
AB  - In this study, the partial section of mitochondrial cytochrome b in 23
      individuals of four Bactrocera cucurbitae geographic populations (Banna, Ruili,
      Yuanjiang, and Hekou)in Yunnan Province was sequenced, and the phylogenetic trees
      of all haplotypes were constructed by means of N-J method, using B. dorsalis, B.
      correct and B. tau as the out-group species. Of the 426 bp mitochondrial
      cytochrome b DNA sequences obtained, A% + T% was about 65.0%, four nucleotide
      sites were substituted, and no base composition of the sequences was inserted and
      lost. Five haplotypes were identified in all the sequences, with four showing
      polymorphism, and one shared. The genetic characters of the four populations were
      analyzed by Fst value and gene flow through Mega software. The Fst value was
      0.16667-0.20000 (P > 0.05), and the Nm value was 2.00 - 2.50. The N-J tree
      suggested that four haplotypes constructed three clades. All results showed that
      the genetic differences presented among the four populations, but with low
      degrees. The main reason causing the genetic differences among the four
      populations was supposed to be related to genetic isolation and ecological
      adaptation.

PMID- 16422511
TI  - [Effects of earthworm activity on phosphorus fraction and available phosphorus
      content in red soil].
AB  - By the methods of incubation test and Hedley's phosphorus fractionation, this
      paper studied the effects of inoculating earthworm (Pheretinma pingi) on the
      phosphorus fractions and available phosphorus contents in red soil. The results
      showed that during a 100-day incubation, earthworm inoculation combined with
      organic materials (rice straw RS, peanut residue PR, and rape residue RR)
      amendment increased significantly the content of soil available phosphorus.
      Statistics analysis showed that there was a significant difference in soil
      available phosphorus content between treatments PR or RR with and without
      earthworm inoculation. Compared with the contents of anion-exchange resin
      P(trace), NaCO3-soluble P(14.5 mg x kg(-1)) and microbial P(1.0 mg x kg(-1)) in
      CK, those in treatments of earthworm inoculation plus organic materials amendment
      increased to 10.5 - 17.8 mg kg(-1), 23.5-35.6 mg x kg(-1), and 6.8 - 9.7 mg x kg(
      1), respectively, organic phosphorus content enhanced from 37.9 mg x kg(-1) to
      50.7-59.3 mg x kg(-1), whereas residual P was reduced. Earthworm performed an
      activated effect on the availability of phosphorus in red soil.

PMID- 16422510
TI  - [Arthropod community structure and its fuzzy clustering analysis in jujube
      orchard].
AB  - Based on the principles of community ecology and by the method of fuzzy
      clustering, this paper studied the temporal and quantitative dynamics of the
      arthropod community and sub-community in jujube orchard (Feidong 2003), aimed to
      utilize natural enemy resources for pest control. There were 52 species of
      arthropod belonging to 47 families in the orchard. Arachnida and Cecidomyidae had
      a higher relative abundance than other families being 0.3465 and 0.2309,
      respectively. The individuals of the arthropod community were the highest on 8
      June and 21 September. The total community and pests-neutral insect sub-community
      could be clustered into 4 clusters, respectively. For total community, the
      clusters (T = 0.92) were those on 22 March, 6 April, 22 November, and on other
      dates, and for pests-neutral insect sub-community, they (T = 0.94) were those on
      22 March, 6 April, 8 June, and on other dates. The natural enemy sub-community
      could be clustered into 3 clusters (T = 0.94), i. e., those on 22 March, on 6
      April, and on other dates. The results of cluster analysis partly reflected the
      seasonal differences of total community and sub-community, while the temporal
      overlaps of cluster results reflected the complexity of community structure.

PMID- 16422512
TI  - [Effects of returning maize straw into field on dynamic change of soil microbial
      biomass C, N and P under different promoted decay condition].
AB  - A 2-year field experiment of wheat-maize rotation was conducted on a cinnamon
      soil of east Hebei Province to study the effects of returning maize straw into
      field on the dynamics of soil microbial biomass C, N and P, and their
      relationships with soil nutrients and enzyme activities. The results showed that
      under the condition of returning maize straw combined with applying chemical
      fertilizer to adjust straw C/N, the application of effective microorganisms could
      increase soil microbial biomass C, N and P in each crop growth period, advance
      their peak time, and better regulate soil nutrient supply, compared with no
      application of effective microorganisms. Soil microbial biomass had a
      significantly positive correlation with soil enzyme activities, but its
      correlation with soil hydrolysable N and available P was strongly affected by
      crop growth and fertilization system.

PMID- 16422513
TI  - [Ecological effects of multifunctional micro-flora agent in environment].
AB  - In this paper, strains ZJY-1 (Brevibacillus brevis) and ZJY-116 (Bacillus
      subtilis) with evident inhibitory effect on Fusarium oxysporum f. sp. cucumerinum
      and with promotion effect on plant growth were screened from cucumber
      rhizosphere, and the feasibility of exerting the ecological effects of
      multifunctional micro-flora agent was studied by treating cucumber seeds with the
      two strains singly or mixed with chlorpyrifos-degrading strain DSP3 (Alcaligenes
      faecali). The results showed that the two strains could keep their functions in
      suppressing disease and promoting plant growth when mixed with DSP3, and the
      chlorpyrifos-degrading effect of DSP3 had no significant difference when DSP3 was
      applied singly or mixed with the two strains. This study testified the
      feasibility of applying multifunctional micro-flora agent in the environment.

PMID- 16422514
TI  - [Phosphorus removal efficiency of Yaonigou constructed wetland on Fuxian
      lakeshore].
AB  - To mitigate and control the eutrophication of the waters in Fuxian Lake bay, 1
      hm2 Yaonigou constructed wetland was built on the north Fuxian lakeshore, and the
      P removal of the wastewater from Yaonigou River was investigated by the
      techniques of precipitation pond, oxidation pond, and subsurface-and surface flow
      constructed wetland. The results demonstrated that this constructed wetland had a
      very strong capacity (7.8% - 81.1%) of total phosphorus (TP) removal. The average
      removal rate of TP was 54.9%, and the TP retention in the constructed wetland was
      265mg x m(-2) x d(-1), of which, plant assimilation was 26.1 mg x m(-2) x d(-1),
      about 10% of the total. The TP removal was mainly through adsorption and
      sedimentation, but the seasonal growth dynamics of main plant Oenanthe javanica
      could have a definite effect on the efficiency of TP removal. During the
      examination, the TP retention capacity was in order of subsurface flow
      constructed wetland > oxidation pond > precipitation pond > surface flow
      constructed wetland.

PMID- 16422515
TI  - [Corresponding analysis on rice grain heavy metal pollution in Fujian province].
AB  - By the methods of environmental statistics and corresponding analysis, this paper
      collected 38 early and late rice grain samples from the middle, southern,
      northern, western and eastern parts of Fujian Province to detect their Hg, As,
      Cr, Cd and Pb contents, and to search for the main factors resulting in the
      difference of rice cropping type in different regions, aiming at further
      understanding the relationships between heavy metal pollution and rice cropping
      type. The results showed that among the test heavy metals in grain, Pb had the
      highest percentage (100%) beyond the standard level, followed by Hg (78.95%), Cd
      (50.5%) and Cu (2.63%), while As did not surpass the standard level. It therefore
      could be concluded that Pb and Cd were the main factors resulting in the
      difference of rice cropping type in different regions. The results also showed
      that 38 rice grain samples could be clustered into 7 groups, indicating that
      different rice cropping types would significantly cause different degrees of
      heavy metal pollution, which suggested that the best way in controlling and
      preventing rice grain heavy metal pollution could be the approach of combining
      site-controlling with variety selection, based on the situation of different
      regions and rice cropping systems.

PMID- 16422516
TI  - [Cd, Cu, Zn and Pb contents and forms in soils and rapeseeds around Wuhu Plant].
AB  - The study showed that around Wuhu Plant, soil Cd, Zn and Pb mainly existed in Fe
      Mn oxide form, and Cu in residual form, with the percentage of 31.81%, 39.83%,
      53.79%, and 46.24%, respectively. Soil exchangeable Cd and Pb had a higher
      proportion (23.47% and 16.32%) than soil exchangeable Cu and Zn (3.14% and
      0.54%). The correlations between soil heavy metals and their forms, as well as
      their transformation to available form were different. Different heavy metals had
      different accumulation trends in rapeseed and its hull. Cu easily accumulated in
      hull, while Cd, Zn and Pb had a higher accumulation in seed. The accumulation
      rate of heavy metals in rapeseed and hull was also different, being the highest
      for Cd. There was a significantly negative correlation (P < 0.05) between the
      accumulation rate of heavy metals and their contents in soil. In rapeseed, Cd, Cu
      and Pb were mainly in sodium hydroxide form, with the percentage of 32.50%,
      22.94% and 34.69%, respectively, while Zn was mainly in EDTA form, with a
      percentage of 45.97. The existed forms of heavy metals in rapeseed probably
      affected their toxicity, but the toxicity to human food could not be inferred
      from this research, and needed to be studied further. There was a weak relation
      between heavy metals contents and their existed forms in rapeseed.

PMID- 16422517
TI  - [Enrichment characteristics of heavy metals in heron eggs].
AB  - In this study, the eggs and tissues of black-crowned night heron, little egret,
      Chinese pond heron and cattle egret were sampled from the Dashu, Yuantong and
      Taizi mountains in Hefei areas of Anhui Province in April to June 2004, and the
      residual amounts of Cd, Pb and Cr in the samples were determined by atomic
      absorption spectrophotometry. The results showed that the test heavy metals could
      be detected at high levels in the eggshell, egg contents, and tissues of most
      samples. Eggshell and bone were the two main sites for heavy metals enrichment.
      Eggshell had significantly higher residues of the heavy metals than egg contents,
      implying that heavy metals could be excreted by eggshells. The residues of heavy
      metals in eggshell ranked as Cr > Pb > Cd, and had significant differences among
      species. Of the three heavy metals, Cr showed the most variation among species,
      being the highest in eggshell of Chinese pond heron and the lowest in that of
      cattle egret, but in egg contents, there was no significant difference among
      species. The variation of Cr residues among species was the second, being the
      highest in the egg contents of Chinese pond heron but not detected in that of
      cattle egret. The residues of Pb among species varied little. Since eggshell was
      easy to collect, it was practical to use it as the indicator to assess the
      pollution status of wetlands.

PMID- 16422518
TI  - [Effects of overlying water properties on sorption of organic pollutants in
      sediments].
AB  - By the method of orthogonal experiment, this paper studied the effects of
      overlying water temperature, pH, ionic strength, and dissolved organic carbon
      (DOC) on the sorption of phenanthrene and pentachlorophenol (PCP) in sediments.
      The results showed that temperature was the main factor affecting the sorption
      behavior of phenanthrene, with the trend of partition coefficient (Kd) decreased
      with temperature. For PCP, its Kd was the smallest at 20 degrees C, and its
      sorption was decreased with pH. The DOC content of overlying water slightly
      decreased the Kd of phenanthrene and PCP, and ionic strength only increased the
      Kd of PCP slightly. The sorption capacity of organic pollutants in sediment was
      mainly determined by the properties of organic pollutants and sediments.

PMID- 16422519
TI  - [Effects of stress duration and non-toxic ions on heavy metals toxicity to
      Arabidopsis seed germination and seedling growth].
AB  - The study on the toxicity of heavy metals Hg2+, Cd+, Cu2+ and Pb2+ to Arabidopsis
      se d germination and seedling growth showed that the test heavy metals had a
      stronger toxicity on seedling growth than on seed germination. The toxicity on
      seedlings was in order of Cu2+ > Hg2+ > Cd2+ /Pb2+, while on seeds was Hg2+ >
      Cd2+ > Pb2+/Cu2+. Seed germination rate was decreased with increasing stress
      duration, and different heavy metals showed different toxicity at different
      stress duration. For example, Hg2+ displayed a stronger toxicity at 12 - 24 h
      stress, while Cd2+ was at 0 - 12 h stress. It seemed that seed coat played an
      important role in seed tolerance to heavy metals. The interaction between non
      toxic ions and heavy metal ions on seed germination showed that Ca2+, Mg2+, K+
      and Na+ at 5 mmol x L(-1) could enhance the toxicity of Hg2+, but did not affect
      Cd2+ toxicity. For seedling growth, Ca2+, Mg2+, K+ and Na+ might enhance the
      toxicity of Hg2+, Ca2+ might alleviate the toxicity of Cd2+ but enhance the
      toxicity of Cu2+ , and K+ might alleviate Pb2+ toxicity. The mechanism of heavy
      metals injury was discussed in the paper.

PMID- 16422520
TI  - [Distribution of nekton stock density and its community structure in Taiwan
      Strait in summer and autumn].
AB  - This research was conducted based on the bottom trawl surveys in Summer and
      Autumn. An analysis on the stock density and community structure of nekton in
      Taiwan Straits indicated that the average stock density was 8.50 kg x h(-1) in
      Summer and 6.94 kg x h(-1) in Autumn. The species number was 80 in Summer and 91
      in Autumn, and the abundance, species diversity index, and evenness index were
      all higher in Autumn than in Summer. The average species diversity index was
      2.0466 in Summer and 2.3964 in Autumn. The dominant species whose index of
      relatively importance (IRI) was > 200 were hairtail (Trichiurus japonicus),
      lanternbelly (Acropoma japonicum), red bigeye (Priacanthus macracanthus), large
      scale lizardfish (Saurida undosquamis) and common Chinese squid (Loligo
      chinensis) in Summer, and hairtail (Trichiurus japonicus), skinnycheek
      lanternfish (Benthosema pterotum), wart perch (Psenopsis anomala), squid (Loligo
      chinensis), white-tipped mackerel scad (Decapterus maruaelsi) and deep pugnose
      ponyfish (Secuter ruconius) in Autumn. As a whole, the aggregated intensity of
      dominant species in Summer was higher than that in Autumn.

PMID- 16422521
TI  - [Microecological distribution of toxin-producing bacteria in Fug rubripes in
      Bohai Sea and biological characteristics of B3B].
AB  - The study showed that toxin-producing bacteria were commonly existed in each part
      of Fugu rubripes body. 19 strains of high poisonous bacteria were isolated from
      its ovary, liver and other tissues, among which, strain B3B was identified as
      genus Bacillus based on its physiological and biochemical characteristics and
      16SrDNA sequence, and could produce tetrodotoxin through mouse test, thinner
      chromatography, and mass spectrography.

PMID- 16422522
TI  - [A comparative study on feeding intensity of two rotifer Brachionus calyciflorus
      strains].
AB  - The study on the feeding intensity and its relationships with food concentration,
      food quality and cultural duration of Guangzhou and Wuhu Brachionus calyciflorus
      strains showed that the filtration and ingestion rates of the rotifers decreased
      with their increasing cultural duration. Within 20 hours, there was a curvilinear
      relationship between the filtration rate of both the two strains and food
      concentration, but a linear relationship between the ingestion rate and food
      concentration. The filtration rate of Guangzhou and Wuhu strains was 0.0029 +/-
      0.0001 ml x ind. (-1) x h(-1) and 0.0039 +/- 0.0008 ml ind. (-1) x h(-1),
      respectively, when fed on Chlorella pyrenoidosa, which were higher than fed on
      the other two types of food. The ingestion rate of Guangzhou strain fed on
      Chlorella pyrenoidosa (0.3992 x 10(4) +/- 0.00850 x 10(4) cell ind. (-1) x h(-1))
      was higher than that fed on Scenedesmus obliquus (0.1670 x 10(4) +/- 0.0370 x
      10(4) cell x ind.(-1) x h(-1)), but each of them was similar with that on mixed
      algae. The ingestion rate of Wuhu strain was not significantly affected by food
      type. The filtration and ingestion rates between the two strains differed with
      food concentration, food type and culture duration.

PMID- 16422523
TI  - [Effects of heavy metal ions on SOD activity of Litopenaeus vannamei
      hepatopancreas, gill and blood].
AB  - This paper studied the effects of Cu2+ , Zn2+ and Cd2+ on the superoxide
      dismutase (SOD) activity of Litopenaeus vannamnei hepatopancreas, gill and blood.
      The results showed that the SOD activity changed significantly with prolonged
      exposure of these ions (P < 0.05). The SOD activity of all test objectives
      changed with a single peak under the exposure of 0.1 - 1 mg Cu2+ x L(-1), that of
      hepatopancreas and of hepatopancreas and gills was inhibited obviously under 10
      mg Zn2+ x L(-1) and 0.5 mg Cd2+ x L(-1), respectively, while 0.25 mg Cd2+ x L(-1)
      had no significant effect on that of gill. The SOD activity of hepatopancreas,
      gill and blood all increased first and then decreased under the prolonged
      exposure of < 10 mg Zn2+ x L(-1) and < 0.25 mg Cd2+ x L(-1). There was an obvious
      dose-time response relationship between test metal ions and SOD activity. The SOD
      activity was decreased in order of hepatopancreas > gill > blood, while the
      toxicity of test metal ions was in order of Cd2+ > Cu2+ > Zn2+.

PMID- 16422525
TI  - [Regulation effects of tourmaline on seawater pH value].
AB  - In this paper, chemical analysis, X-ray diffraction and atomic force microscopy
      were employed to examine the characteristics of tourmaline produced in east Inner
      Mongolia Autonomous Region, and batch experiments were conducted to study its
      regulation effects on seawater pH value. The factors affecting the regulation,
      such as the dosage of tourmaline and the salinity and initial pH value of
      seawater, were also studied. The results showed that tourmaline could regulate
      the seawater pH value from its initial 3 and 10 to 7.1 and 8.9, respectively, and
      the regulation effect was greater in the seawater with lower salinity, e.g.,
      after 120 minutes treatment, the initial pH value (5.0) of the seawater with a
      salinity of 5, 10, 15, 20 and 35 was increased by 3.24, 3.16, 3.06, 2.99 and 2.85
      unit, respectively. Tourmaline had little effect on seawater conductivity. This
      study would provide an experimental base for the application of tourmaline in
      aquaculture.

PMID- 16422524
TI  - [Toxicity effects of pentachlorophenol on Brachydanio rerio].
AB  - With embryo development technique, this paper determined the toxicity of
      pentachlorophenol (PCP) to Brachydanio rerio embryos. The results showed that the
      special effect duration of PCP on embryos was within 6 hours after embryos
      incubation. PCP could markedly inhibit the development of Brachydanio rerio
      embryos, and cause its malformation and even death. There were different toxicity
      endpoints which could be observed in embryos exposed to PCP with different time.
      The lethal effect sensitivity of embryos incubated after 48 hours was getting
      lower when the exposure time was getting shorter, the LC50 being the minimum
      (70.8 microg x L(-1)) for 0 hpf embryos, and the maximum (831.8 microg x L(-1))
      for 24 hpf embryos. The acute toxicological endpoint of Brachydanio rerio embryos
      was in order of edema, no blood-circulation and heartbeat > incubation rate >
      stopping growth, and the most sensitive endpoints of Brachydanio rerio embryos to
      pentachlorophenol were no blood-circulation and half lethal concentration at 48
      hrs.

PMID- 16422526
TI  - [Research advances in ecosystem flux].
AB  - To develop the long-term localized observation and investigation on ecosystem
      flux is of great importance. On the basis of generalizing the concepts and
      connotations of ecosystem flux, this paper introduced the construction and
      development histories of Global Flux Networks, Regional Flux Networks (Ameri
      Flux, Euro-Flux and Asia-Flux) and China-Flux, as well as the main methodologies,
      including micrometeorological methods (such as eddy correlation method, mass
      balance method, energy balance method and air dynamic method)and chamber methods
      (static and dynamic chamber methods), and their basic operation principles. The
      research achievements, approaches and advances of CO2, N2O, CH4, and heat fluxes
      in forest ecosystem, farmland ecosystem, grassland ecosystem and water ecosystem
      were also summarized. In accordance with the realities and necessities of
      ecosystem flux research in China, some suggestions and prospects were put
      forward.

PMID- 16422527
TI  - [Biological effects of rare earth elements and their action mechanisms].
AB  - This paper reviewed the effects of rare earth elements on plant root development,
      biomass, quality, and resistance against stress. Applying appropriate amount of
      rare earth elements could not only promote seed germination and root development,
      increase plant biomass, but also improve harvest quality and plant resistance
      against stress. The plant uptake characteristics of rare earth elements, as well
      as their contents, distribution, existing forms, and cytolocalization in plants
      were discussed, with the focus on the effects of rare earth elements on
      photosynthesis and chlorophyll formation, nutrient uptake, relationships between
      rare earth elements and calcium, and action mechanisms of rare earth elements on
      cell membrane and enzymes. Rare earth elements could enhance chlorophyll content
      and improve photosynthetic rate, and thus, could increase plant biomass. When an
      appropriate amount of rare earth elements was applied, the uptake of nutrients by
      plant and their transformation and utilization were promoted. Rare earth elements
      could replace calcium ion to participate in enzymatic reactions, maintain the
      osmosis and stability of cell membrane, promote the protection function of cell
      membrane, and enhance the plant resistance capability against stress. In the end,
      further researches on rare earth elements were suggested.

PMID- 16422529
TI  - [Application of chemical ecology in controlling marine fouling organisms].
AB  - Many marine organisms can produce secondary metabolites beneficial to the
      protection of marine environments against fouling, and thus, applying chemo
      ecological methods to extract the natural antifoulants from marine organisms to
      resolve the problems relevant to marine fouling is a new thinking in resent
      years. Its aim is to search for high efficient and non-toxic antifoulants to
      replace the existing chemically synthetic ones which are unfortunately found to
      have widespread toxic effects on marine environment. Although we know few about
      the antifouling mechanisms of secondary metabolites, many natural products have
      been proved to have antifouling activity. Therefore, basic and applied researches
      on the ecological roles of these natural compounds, their action mechanisms,
      coating compatibility, controlled release, and field test are required in the
      future.

PMID- 16422528
TI  - [Advances in research on in situ chemo-immobilization of heavy metals in
      contaminated soils].
AB  - In situ immobilization of heavy metals is a main method for decreasing the
      mobility and bioavailability of heavy metal ions through their immobilization by
      adding various amendments. Due to its easy operation and rapid efficiency, this
      method is becoming non-replaceable, especially for the remediation of non-point
      polluted arable soils. Natural materials and industrial by-products with high
      capacity of entrapping and fastening heavy metals, e. g., phosphorite, peat,
      lime, and organic fertilizers, can be obtained and employed, and the
      immobilization efficiency of these amendments as well as the environmental risk
      of the ionic leaching, releasing, and biological toxicity of heavy metals could
      be evaluated in laboratory and field. In this paper, the resources and types of
      the amendments were classified, and the possible immobilization mechanisms for
      the remediation of heavy metals- contaminated soils were discussed. The
      assessment methods of this remediation in laboratory and field were formulized,
      its limitation was analyzed, and further development directions were put forward.

PMID- 16422530
TI  - [General principles of urban ecological land classification and planning].
AB  - Urban ecological land planning is a difficult and urgent task in city layout.
      This paper presented the definition of urban ecological land, and according the
      definition, divided the urban ecological land into two groups, i. e., ecological
      land for service, and ecological land for functioning. Based on the principles of
      city layout, some measures to plan these two urban ecological land groups were
      proposed.

PMID- 16422531
TI  - [Development of the study on germplasm resources of medicinal plants:
      construction of core collection].
AB  - According to the successful experience of studying on crops, this paper
      introduced the conception of the core collection of medicinal plants, and
      analyzed the characteristic and the way to construct it. Studies on the core
      collection would fulfill the management and utilize the germplasm resources
      conveniently and provide a new idea and a method to study on the germplasm
      resources of medicinal plants. It is necessary to study on the core collection
      for the development of the germplasm resources of medicinal plants.

PMID- 16422532
TI  - [Studies of commonly used traditional medicine-ginger].
AB  - To review the chemical, pharmacological, studies on ginger (Zingiber officinale)
      in the last ten years, and also its processing history and clinical uses.
      Gingerols and related compounds in ginger have many pharmacological activities.
      Chemical studies should be given sufficiently emphasis, and advances of the
      chemical study will promote the other related researches to develop in depth.

PMID- 16422533
TI  - [New study progress of sinomenine].
AB  - To further understand sinomenine, this paper has introduced the abstract
      technology, assaying, pharmaceutical chemistry, pharmacological action,
      pharmacotoxicology, pharmacokinetics and clinical application of sinomenine based
      on the important and significant contents of reference which have been consulted
      in the past ten years. Sinomenine is a kind of non-steroidal anti-inflammatory
      drugs with very effective and little side effect and expected it as a good new
      drug withdrawal medicine in the future.

PMID- 16422534
TI  - [Study on quantified relationship between contents of active components in
      Forsythia suspense and nutrition of soil].
AB  - OBJECTIVE: To sift the main effective factors of active component of Forsythia
      suspense. METHOD: The active component of F. suspense was mensurated by HPLC, and
      the contents of nutrition in soil was determined by conventional methods. The
      active component of F. suspense and the nutrition of soil collected from
      different regions was analyzed by SPSS 11.0 for windows software package.
      Accounted the partial correlation coefficients of soil factor to the active
      component of F. suspense, and established regression equations. RESULT: Soil
      available phosphorus is the most important factor that effected forsythiaside
      content in the seeds of F. suspense, followed by kalium, pH, FACT; Forsythin in
      the seeds of F. suspense is mainly effected by soil abailable kalium and FACT; pH
      is the important factor effected Forsythinin in F. suspense, followed by soil
      available phosphorus, soil available kalium, and FACT; and the main
      effectivefactors of forsythiaside in F. suspense are soil available phosphorus,
      soil available kalium. CONCLUSION: The contents of nutrition in soil is one of
      important factors which affect the active component of F. suspense.

PMID- 16422535
TI  - [Studies on micromorphological characters of fruit coats in cultivated Fructus
      Trichosanthis in Shandong Province].
AB  - OBJECTIVE: To explore the affinity relation among land race of Trichosanthes
      kirilowii and to provide evidence tor the classification and authentication.
      METHOD: Using scanning electron microscope, characteristics of the pericarp
      surface were studied comparatively. RESULT: The pericarp surface of the
      cultivated Fructus Trichosanthis in Shandong showed the characteristics of
      generality and diversity. CONCLUSION: The results of the study could be used for
      the identification of the cultivated Fructus Trichosanthis in Shandong.

PMID- 16422536
TI  - [Studies on the seed embryo germination and propagation of Dendrobium candidum in
      vitro].
AB  - OBJECTIVE: To determine optimum culture conditions for the seed embryo culture
      and rapid propagation of Dendrobium candidum. METHOD: Seed embryos of D. candidum
      were incubated in the medium containing a combination of 6-benzylaminopurine (BA)
      and 1-naphthaleneacetic acid (NAA), potato extract, banana extract and activated
      carbon in order to induce seed embryo germination, protocorm differentiation,
      plantlet propagation and plantlet rooting. RESULT AND CONCLUSION: The maximum
      embryo germination percentage was obtained in the 1/2 MS media supplemented with
      20% potato extract. The 1/2 MS medium supplemented with 1.0 mg x L(-1) BA and 0.1
      mg x L(-1) NAA was very beneficial to the protocorm differentiation and
      propagation of D. candidum. The highest protocorm propagation index was obtained
      from the medium containing the activated carbon. The highest root numbers and
      length were observed in plants growing in 1/2 MS medium containing 0.5 mg x L(-1)
      NAA.

PMID- 16422537
TI  - [Orthogonal experiments to select spraying granulation technique for Baoshen
      granules].
AB  - OBJECTIVE: To raise the end-product and economical efficiency of spraying
      granulation, we demand screening preparation technique. METHOD: Adopting newly
      spraying granulation technique, taking extracting technique, adhesive material,
      temperature of exit and entry,and the matching of accessories as inspecting
      factors, two levels of each factors, end-product as inspecting marker, we
      selected the best Baoshen granules preparation technique by orthogonal design.
      RESULT: Among the 4 factors, adhesive material is most notable, next is
      temperature of exit and entry, the other two is of little importance. CONCLUSION:
      The optimum spraying granulation technique of Baoshen granules is A2B1C2D1.

PMID- 16422538
TI  - [Chemical constituents from Elsholtzia blanda].
AB  - OBJECTIVE: To investigate the constituents of Elsholtzia blanda. METHOD: The
      chemical components were isolated by polyamide and silica gel column
      chromatography. Their structures were identified with extensive spectral (EI-MS,
      ESI-MS, 1H-NMR, 13C-NMR, DEPT, 1H-1H-COSY, HMBC, HMQC) and chemical methods.
      RESULT: Five compounds were isolated and identified as luteolin (I), luteolin-5-O
      beta-D-glucopyranoside (II), luteolin-7-O-beta-D-glucopyranoside (III), 5-hydroxy
      7, 8 -dimethoxyflavone (IV) and 5-hydroxy-6, 7-dimethoxyflavone (V). CONCLUSION:
      Compounds III, IV, V were isolated from E. blanda for the first time and I was
      firstly separated from the genus Elsholtzia.

PMID- 16422540
TI  - [Determination of hedychenone in Hedychium yunnanense].
AB  - OBJECTIVE: To establish an HPLC method for determination of hedychenone in
      Hedychium yunnanense. METHOD: C18 Chromatographic column was used, acetonitrile
      water (9:1) as mobile phase, at flow rate of 1.0 mL x min(-1): The wavelength for
      detection was 235 nm. RESULT: The linear range of hedychenone was 5.92-29.6
      microg x mL(-1)(r = 0.9999). The average recovery was 99.0%, RSD of precision was
      less than 2%. CONCLUSION: The method is simple, effective and feasible, and can
      be used to evaluate the quality of the herb.

PMID- 16422539
TI  - [Phenolic acid derivatives from the rhizome of Fagopyrum cymosum].
AB  - OBJECTIVE: To study the chemical constituents of Fagopyrum cymosum. METHOD: The
      chemical constituents were isolated by various chromatographic methods and their
      structures were elucidated by the analysis of spectral data and physiochemical
      properties. RESULT: Four phenolic acid derivatives were isolated from F. cymosum.
      The chemical structures were elucidated as trans-p-hydroxy cinnamic methyl ester
      (I), 3, 4-dihydroxy benzamide (II), protocatechuic acid (III), protocatechuic
      acid methyl ester (IV). CONCLUSION: Compounds I, II, IV were obtained from the
      genus Fagopyrum for the first time.

PMID- 16422541
TI  - [Study on the chemical constituents in herb of Hypericum attenuatum].
AB  - OBJECTIVE: To study the constituents of Hypericum attenatum. METHOD: The
      compounds were isolated by chromatography on silica gel, the structures were
      identified by their physical, chemical properties and IR, NMR and MS spectral
      data respectively. RESULT: Nine compounds were isolated and identified as p
      hydroxybenzoic acid (1), 6, 9-dihydroxy-4, 7-megastigmadien-3-one (2), butyl
      alcohol-O-alpha-D-fructoside (3), 24-ethyl-cholest-7-ene-3 beta, 5 alpha, 6 beta
      thtroil (4), hexanol (5), 1 beta, 6 alpha-dihydroxyeudesmane-4(14)-ene (6), beta
      sitosterol (7), 5, 5-dimethyl-4-hydroxy-tetrahydrofuran-2-one (8), beta
      daucosterol (9). CONCLUSION: All of the compounds were isolated from H.
      attenuatum for the first time.

PMID- 16422542
TI  - [Effect of the Yifuning soft gelatin capsules on estrogen receptor and nitric
      oxide levels in ovariectomized rats].
AB  - OBJECTIVE: To investigate the effects of the Yifuning soft gelatin
      capsules(YFN)on estrogen receptor (ER) and nitric oxide (NO) levels in
      ovariectomized rats. METHOD: Fifty female mature sprague-dawley rats were
      randomly divided into 5 groups: normal control; model control; diethylstilbestrol
      tablets (DT); YFN (high dose and low dose). After 4 weeks' treatment, the serum
      E2 levels were detected by radioimmunoassay. The estrogen receptor (ER) levels of
      uterus and artery were detected with method of radioligand binding assay of
      receptor (RBAR). The uterus pathologic changes were investigated with light
      microscope. NO and NOS levels of the artery and the uterus index were detected
      too. RESULT: YFN can obviously improve serum E2, increase index and ER of uterus
      (P < 0.01 or P < 0.05), and ameliorate the uterus' pathologic changes in OVX
      rats. It also can increase the artery' ER, NO and NOS levels. CONCLUSION: YFN can
      cure the climacteric syndrome and prevent the cardiovascular disease after post
      menopause.

PMID- 16422543
TI  - [Antioxidant and anti-inflammatory effects of cyanidin from cherries on rat
      adjuvant-induced arthritis].
AB  - OBJECTIVE: To assess the possible antioxidant and anti-inflammatory activity of
      cyanidin from cherries on adjuvant induced arthritis (AA) in SD rats. METHOD:
      Arthritis was induced by the complete Freud's adjuvant in male Sprague Dauley
      rats and assessed based on paw swelling. Rats were randomly divided into normal
      group (NM), adjuvant arthritis group (AA) and three cyanidin-treated groups in
      high dosage (HA), middle dosage (MA), and low dosage (LA). The morphological
      changes in the hind limbs were conducted under a light microscope. We detected
      glutathione (GSH) in whole blood and malonaldehyde (MDA), superoxide dismutase
      (SOD), total antioxidative capacity (T-AOC) activity in serum by special kits to
      assess the antioxidant effects of cyanidin on AA. Moreover, the prostaglandin E2
      (PGE2) levels in paw tissues were determined by radioimmunoassay and TNF-alpha
      levels in serum were determined using ELISA kits specific for rat. RESULT: The
      cyanidin could protect against the paws swelling in AA rats. From the day 14
      after AA induction, the swellings of the cyanidin treated groups at high dosage
      and low dosage were significantly reduced compared with the model group (P <
      0.05, 0.01). Histological examination of sections through the hind limbs revealed
      alleviation of inflammatory reaction in the joint after the treatment. The
      cyanidin at high and low dosage could increase the GSH, SOD activity and T-AOC
      levels in whole blood or serums and decrease MDA in AA rats (P < 0.01). The
      cyanidin could decrease the PGE2 levels in paw tissues and the TNF-alpha levels
      in serum at high and low dosages (P < 0.01). CONCLUSION: The cyanidin could
      protect against the paws swelling in AA rats, and alleviate the inflammatory
      reaction in the joint, and the mechanism might be via the increase activity of
      GSH, SOD and T-AOC that improve the total antioxidative capacity and scavenge the
      free radicals, perhaps as a result of that the levels of the PGE2 in paw tissues
      and TNF-alpha contents in serum were decreased. The results suggest that the
      cyanidin from cherries could be one of the potential candidates for the
      alleviation of arthritis.

PMID- 16422544
TI  - [Effects of components isolated from Astragalus mongholicus on expression of p
      selectin in shock wave induced kidney injury in rabbit model].
AB  - OBJECTIVE: To investigate the effective components of Astragalus mongholicus and
      their mechanisms in alleviating extracorporeal shock wave lithotripsy (ESWL)
      induced kidney injury. METHOD: 69 male rabbits were randomly assigned into
      control group, sham treatment group, Total Saponins of Astragalus (TSA) group,
      Total Flavonoids of Astragalus (TFA) group, and Total Polysaccharide of
      Astragalus group (TPA). The shock wave treated kidneys were observed for the
      expression of p-selectin and the change of cells ultrastructure pre and post
      ESWL. The concentration of Maleic Dialdehyde (MDA) as well as activity of
      superoxide dismutase (SOD) in the kidney tissues was also analyzed. RESULT: After
      application of shock wave treatment, p-selectin was expressed extensively in
      renal glomerulus, renal tubules and renal interstitium of the treated kidneys. It
      showed a significant increase of MDA levels and decrease of SOD activity in
      control group (P < 0.05) after ESWL. The comparison between controls and TSA
      group demonstrated that TSA could significantly reduce the positive rate of p
      selectin P < 0.05) and alleviate the injuries of cells ultrastructure. The
      results also showed a significant decrease of MDA levels and increase of SOD
      activity in TSA group compared to controls (P < 0.05). The protective effects of
      TFA and TPA in alleviating kidney injury induced by shock wave were lower than
      those of TSA; they had no effects of the expression of P-selectin. CONCLUSION:
      TSA is the main components of A. mongholicus in alleviating shock wave induced
      kidney injury not only by scavenging oxygen free radicals but also inhibiting the
      expression of p-selectin.

PMID- 16422545
TI  - [Pharmacokinetic study of intraperitoneal chemotherapy with HCPT].
AB  - OBJECTIVE: To study the pharmacokinetic of 10-Hydroxycamptothecin HCPT by
      intraperitoneal administration. METHOD: Six dogs were given HCPT by
      intraperitoneal perfusion: HCPT 2 mg x kg(-1), dissolved in 300 mL NS. During the
      course of experiments, peritoneal fluids and blood were sampled using a
      standardized protocol. The concentration of HCPT in all samples was determined by
      high performance liquid chromatography (HPLC). RESULT: The area under the curve
      (AUC) of peritoneal fluids was significantly highly as compared to the AUC of
      femoral vein and portal vein (P < 0.001). CONCLUSION: These experiments
      demonstrate that intraperitoneal chemotherapy has significant effect on the
      pharmacokinetics of IP route of HCPT administration. This method should be a more
      reasonable chemotherapy for the prevention of recurrence and liver metastasis of
      gastric cancer, colon cancer and ovary cancer after radical resection.

PMID- 16422546
TI  - [Development of an animal model of blood stasis syndrome and thrombosis].
AB  - OBJECTIVE: To develop an animal model of thrombosis and blood stasis syndrome in
      rats by using lipopolysaccharide (LPS) in combination with carrageenan (Ca).
      METHOD: SD rats in control group were randomly divided into control group and
      model group (LPS/Ca treatment). The rats in model group were firstly treated with
      Ca ip, and followed by LPS iv sixteen hours later. The rats in control group were
      given normal saline (NS). The moment of LPS iv was served as 0 h for the
      observation. The ear microcirculation, blood rheology parameters (whole blood
      viscosity etab, plasma viscosity etap and platelet aggregation PA), cruor
      parameters (thrombin time TT, prothrombin time PT, and partial thromboplastin
      time APIT) and inflammation factors (TNFalpha, IL-6) were observed at different
      time after treatment. RESULT: LPS/Ca combinatory treatment can induce a stable
      and repeatable thrombosis animal model. The thrombus can be observed on the tails
      of rats by naked eyes, and can be quantitatively measured without necessary of
      autopsy. Obstacle in microcirculation, increase in whole blood viscosity (etab)
      and a change of platelets aggregation (PA) rate were observed after LPS/Ca
      treatment. Cruor parameters were significantly prolonged due to large consumption
      of cruor factors and platelets. The concentration of inflammation factors
      TNFalpha and IL-6 in blood was obviously increased at the early stage of the
      model. The results indicate that this animal model has the characteristics of
      blood stasis syndrome caused by pyrogen and toxin accompanied by thrombosis.
      CONCLUSION: LPS/Ca combinatory treatment can induce a easily practicable and
      repeatable animal model characterized as thrombosis and blood stasis syndrome

PMID- 16422548
TI  - [Effect of Kanglaite injection oncyclooxygenase activity in lung carcinoma A549
      cell].
AB  - OBJECTIVE: To study the effect of Kanglaite injection on cyclooxygenase activity
      in lung carcinoma A549 cells. METHODS: The expression of mRNA of COX-1 and COX-2
      were measured by RT-PCR. The expression of COX-2 protein was measured by Western
      blot. RESULT: Kanglaite injection could selectively decreased COX-2 mRNA
      expression and protein expression while COX-1 mRNA expression was unchanged.
      CONCLUSION: Kanglaite injection is selectively inhibitory agent of COX-2, and
      possess inhibitory effects on cyclooxygenase 2.

PMID- 16422549
TI  - Patient safety.

PMID- 16422547
TI  - [Effects of ginsenoside Rh2(GS-Rh2) on cell cycle of Eca-109 esophageal carcinoma
      cell line].
AB  - OBJECTIVE: To investigate the effects of ginsenoside Rh2 (GS-Rh2) on growth
      inhibition and cell cycle of Eca-109 esophageal carcinoma cell line in culture.
      METHOD: The effects of GS-Rh2 on cell growth inhibition was detected by MTT
      assay. Cell cycle was analyzed by flow cytometry (FCM). Cell morphology was
      observed by a light microscope after HE staining. The protein expression of cell
      cycle components (cyclinE, CDK2, p21WAF1) were examined by immunocytochemistry
      and Western blot. The mRNA expression were examined by semiquantitative RT-PCR.
      RESULT: GS-Rh2 inhibited the proliferation of Eca-109 cells in dose and time
      dependent manners. The inhibition rate was about 50% after 1-day treatment with
      20 microg x mL(-1) GS-Rh2 x 20 microg x mL(-1) GS-Rh2 induced the mature
      differentiation and morphological reversion. With increasing dose of GS-Rh2
      treatment, the cell number of G0/G1 phase was increased, whereas it decreased at
      S and G2/M phase. There was significant difference between 10, 20 microg x mL(-1)
      GS-Rh2 groups and the corresponding group without GS-Rh2 treatement. After
      treating cells by 20 microg x mL(-1) GS-Rh2 for 1, 2, 3 days individually, the
      protein and mRNA expression of both cyclinE and CDK2 reduced, while the
      expression of p21WAF1 enhanced gradually. CONCLUSION: GS-Rh2 could arrest Eca-109
      cells at G0/G1 phase and induce cell differentiation tending to normal.
      Furthermore, GS-Rh2 had an effect on expression of cell cycle components
      (cyclinE, CDK2 and p21WAF1) to inhibit Eca-109 cell proliferation.

PMID- 16422550
TI  - A very easy death.

PMID- 16422551
TI  - Can short be long enough? A new perspective in the duration of treatment for
      community-acquired pneumonia.

PMID- 16422552
TI  - Education in end-of-life care: bridging disciplinary and institutional
      boundaries.
AB  - This paper describes the development of an interdisciplinary, interinstitutional
      seminar in palliative care for South Dakota students in medicine, nursing,
      pharmacy, chaplaincy, and social work. Student outcomes from six seminars
      conducted during 2001-2004 are reported, and recommendations for future
      educational efforts are outlined.

PMID- 16422553
TI  - Total victory in California.

PMID- 16422554
TI  - Bird flu plan may not fly.

PMID- 16422555
TI  - Single-player proponents ramp up campaign.

PMID- 16422556
TI  - Privatization fight fuels Canadian election.

PMID- 16422557
TI  - A work in progress.

PMID- 16422558
TI  - Universal lessons.

PMID- 16422559
TI  - The torch has passed.

PMID- 16422560
TI  - Al-H bond formation in hydrated aluminum oxide cluster anions.
AB  - Quantum chemical calculations have been performed to investigate the interaction
      of a water molecule with gas phase aluminum oxide cluster anions. While oxygen
      rich clusters (AlxOy-,x<y) (including Al2O3- which resembles the stoichiometry of
      bulk alumina) form hydroxides as the end product, many aluminum-rich clusters
      (AlxOy-,x>y) generate metal hydrides. These hydride species are, in many cases,
      30-35 kcal/mol more stable than their hydroxide counterparts. Our observations on
      such competing reaction pathways may be useful to understand the catalytic role
      of alumina nanoparticles in many chemical reactions.

PMID- 16422561
TI  - Electronic structure and prediction of atomization energy of naked homoleptic
      uranium hexacarbonyl U(CO)6.
AB  - Our ab initio all-electron fully relativistic Dirac-Fock and nonrelativistic
      Hartree-Fock self-consistent field (SCF) calculations predict the octahedral (Oh)
      uranium hexacarbonyl U(CO)6 to be bound with the calculated atomization energy of
      49.84 and 48.76 eV at the predicted U-C bond lengths (assuming the C-O bond
      distance fixed at 1.17 A) of 2.53 and 2.63 A, respectively. Moreover, our all
      electron fully relativistic Dirac-Fock SCF calculations predict U(CO)6 to be
      lower in energy by 3.90 eV with respect to dissociation into U plus six CO
      ligands. We predict U(CO)6 (Oh) to be very stable in view of our predicted large
      atomization energy (approximately 49 eV) and stability (approximately 4 eV) with
      respect to dissociation into U plus six CO molecules. Innovative techniques
      should be devised for the synthesis of uranium hexacarbonyl since the usual
      synthetic methods have failed so far for this naked actinide hexacarbonyl.

PMID- 16422562
TI  - Visualizing the transient electroosmotic flow and measuring the zeta potential of
      microchannels with a micro-PIV technique.
AB  - We have demonstrated a transient micro particle image velocimetry (micro-PIV)
      technique to measure the temporal development of electroosmotic flow in
      microchannels. Synchronization of different trigger signals for the laser, the
      CCD camera, and the high-voltage switch makes this measurement possible with a
      conventional micro-PIV setup. Using the transient micro-PIV technique, we have
      further proposed a method on the basis of inertial decoupling between the
      particle electrophoretic motion and the fluid electroosmotic flow to determine
      the electrophoretic component in the particle velocity and the zeta potential of
      the channel wall. It is shown that using the measured zeta potentials, the
      theoretical predictions agree well with the transient response of the
      electroosmotic velocities measured in this work.

PMID- 16422563
TI  - An ab initio potential surface describing abstraction and exchange for H+CH4.
AB  - We report an ab initio-based global potential energy surface for H+CH4 that
      describes the abstraction and exchange reactions. The PES, which is invariant
      with respect to any permutation of five H atoms, is a fit to 20,728 electronic
      energies calculated using the partially spin-restricted coupled-cluster method
      (RCCSD(T)) with a moderately large basis (aug-cc-pVTZ). A first set of
      quasiclassical trajectory calculations using this PES are reported for the H+CD4-
      >HD+CD3 reaction at collision energies of 0.65 and 1.52 eV and are compared to
      experiment and recent direct dynamics calculations done with density functional
      theory.

PMID- 16422564
TI  - Atomic-scale rectification at microwave frequency.
AB  - Microwave of known amplitude and frequency, irradiating the junction of a low
      temperature scanning tunneling microscope, was found to induce a dc signal. This
      rectification current is spatially localized and exhibits chemical sensitivity at
      the atomic scale. Dependence of the rectification current on the sample bias
      voltage reveals spin splitting in the electronic state of a single Mn atom and
      vibrations of single MnCO molecule. These results demonstrate the feasibility of
      atomic scale nonlinear spectroscopy and the potential for the detection of
      resonance phenomena excited with a spatially extended electromagnetic wave.

PMID- 16422565
TI  - Optimal dynamic discrimination of similar [corrected] quantum systems in the
      presence of decoherence.
AB  - Optimal dynamic discrimination (ODD) of a mixture of similar quantum systems with
      time series signals enables the extraction of the associated concentrations with
      reasonable levels of laser-pulse noise, signal detection errors, and imperfect
      signal detector resolution [Li et al., J. Chem. Phys. 122, 154103 (2005)]. The
      ODD paradigm is reexpressed in the density-matrix formulation to allow for the
      consideration of environmental decoherence on the quality of the extracted
      concentrations, along with the above listed factors. Simulations show that
      although starting in a thermally mixed state along with decoherence can be
      detrimental to discrimination, these effects can be counteracted by seeking a
      suitable optimal control pulse. Additional sampling of the temporal data also
      aids in extracting more information to better implement ODD.

PMID- 16422566
TI  - Simulating rare events in equilibrium or nonequilibrium stochastic systems.
AB  - We present three algorithms for calculating rate constants and sampling
      transition paths for rare events in simulations with stochastic dynamics. The
      methods do not require a priori knowledge of the phase-space density and are
      suitable for equilibrium or nonequilibrium systems in stationary state. All the
      methods use a series of interfaces in phase space, between the initial and final
      states, to generate transition paths as chains of connected partial paths, in a
      ratchetlike manner. No assumptions are made about the distribution of paths at
      the interfaces. The three methods differ in the way that the transition path
      ensemble is generated. We apply the algorithms to kinetic Monte Carlo simulations
      of a genetic switch and to Langevin dynamics simulations of intermittently driven
      polymer translocation through a pore. We find that the three methods are all of
      comparable efficiency, and that all the methods are much more efficient than
      brute-force simulation.

PMID- 16422567
TI  - Accurate magnetic exchange couplings in transition-metal complexes from
      constrained density-functional theory.
AB  - We demonstrate an accurate method for extracting Heisenberg exchange-coupling
      constants (J) from density-functional theory (DFT) calculations. We note that the
      true uncoupled low-spin state of a given molecule should be identified with the
      ground state of the system subject to a constraint on the spin density of the
      atoms. Using an efficient optimization strategy for constrained DFT we obtain
      these states directly, leading to a simple, physically motivated formula for J.
      Our method only depends on state energies and their associated electron densities
      and assigns no unphysical meaning to the Kohn-Sham determinant or individual
      orbitals. We study several bimetallic transition-metal complexes and find that
      the constrained DFT approach is competitive with, if not better than, the best
      broken symmetry DFT results. The success of constrained DFT in these cases
      appears to result from a balanced elimination of self-interaction error and
      static correlation from the simulation.

PMID- 16422568
TI  - Interaction energies in hydrogen-bonded systems: a testing ground for subsystem
      formulation of density-functional theory.
AB  - The formalism based on the total energy bifunctional (E[rhoI,rhoII]) is used to
      derive interaction energies for several hydrogen-bonded complexes (water dimer,
      HCN-HF, H2CO-H2O, and MeOH-H2O). Benchmark ab initio data taken from the
      literature were used as a reference in the assessment of the performance of
      gradient-free [local density approximation (LDA)] and gradient-dependent
      [generalized gradient approximation (GGA)] approximations to the exchange
      correlation and nonadditive kinetic-energy components of E[rhoI,rhoII]. On
      average, LDA performs better than GGA. The average absolute error of calculated
      LDA interaction energies amounts to 1.0 kJ/mol. For H2CO-H2O and H2O-H2O
      complexes, the potential-energy curves corresponding to the stretching of the
      intermolecular distance are also calculated. The positions of the minima are in a
      good agreement (less than 0.2 A) with the reference ab initio data. Both
      variational and nonvariational calculations are performed to assess the energetic
      effects associated with complexation-induced deformations of molecular electron
      densities.

PMID- 16422569
TI  - Orbital-free tensor density functional theory.
AB  - We propose a family of time-dependent orbital-free density-based theories that go
      beyond the usual current-density description of electrons or other particles. The
      theories deal with physical quantities that characterize the one-particle density
      matrix and consequently the kinetics of the particles. We analyze the first two
      theories in the family. The "lowest-order" theory is quantum hydrodynamics. The
      second one yields not only the longitudinal plasmon collective excitations, but
      also the transverse phonon modes that are associated with elementary excitations
      in Fermi liquids. The theories should make it feasible to do large orbital-free
      simulations of time-dependent and stationary systems.

PMID- 16422570
TI  - Three-pulse photon echo of an excitonic dimer modeled via Redfield theory.
AB  - In this article the third-order response of an excitonically coupled dimer is
      studied. The three-pulse photon echo signals were calculated by extracting
      polarization components from the total polarization in the corresponding phase
      matched directions. The total nonlinear response was obtained by numeric
      propagation of the density matrix, with the exciton-vibrational coupling modeled
      via Redfield relaxation theory. The full two-dimensional three-pulse photon echo
      signals and the peak shift were analyzed in terms of the density-matrix dynamics
      of coherence dephasing and population relaxation. The location of the two-exciton
      state was found to be essential for proper modeling of the three-pulse photon
      echo. In particular, an oscillation in the three-pulse photon echo peak shift is
      found if the two-exciton state is displaced. The oscillations can be related to
      the dynamics of the one-exciton coherences.

PMID- 16422571
TI  - Thermally activated escape rate for a Brownian particle in a double-well
      potential for all values of the dissipation.
AB  - The translational Brownian motion in a (2-4) double-well potential is considered.
      The escape rate, the position correlation function and correlation time, and the
      generalized susceptibility are evaluated from the solution of the underlying
      Langevin equation by using the matrix-continued fraction method. The escape rate
      and the correlation time are compared with the Kramers theory of the escape rate
      of a Brownian particle from a potential well as extended by Mel'nikov and Meshkov
      [J. Chem. Phys. 85, 1018 (1986)]. It is shown that in the low-temperature limit,
      the universal Mel'nikov and Meshkov expression for the escape rate provides a
      good estimate of both escape rate and inverse position correlation time for all
      values of the dissipation including the very low damping (VLD), very high damping
      (VHD), and turnover regimes. Moreover, for low barriers, where the Mel'nikov and
      Meshkov method is not applicable, analytic equations for the correlation time in
      the VLD and VHD limits are derived.

PMID- 16422572
TI  - Nuclear-spin relaxation in nonrigid molecules: discrete multisite local dynamics
      combined with anisotropic molecular reorientation.
AB  - Nuclear-spin relaxation is considered in a molecular system undergoing two types
      of dynamic processes: asymmetric-top small-step rotational diffusion and discrete
      multisite local jumps. The two processes are assumed to be uncorrelated. Time
      correlation functions for relevant rank-two interactions and corresponding
      spectral density functions are derived for a general relation between the
      characteristic rate constants. In addition, limiting cases of fast and slow local
      motions and of some specific jump conditions are also investigated.

PMID- 16422573
TI  - Statistical mechanical theory for steady state systems. IV. Transition
      probability and simulation algorithm demonstrated for heat flow.
AB  - Two microscopic transition theorems are given for the probability of
      nonequilibrium work performed on a subsystem of a thermal reservoir along the
      trajectory in phase space of the subsystem. The resultant transition probability
      is applied to the case of heat flow down an applied temperature gradient. A
      combined molecular dynamics and Monte Carlo algorithm is given for such a
      nonequilibrium steady state. Results obtained for the thermal conductivity are in
      good agreement with previous Green-Kubo and nonequilibrium molecular dynamics
      results.

PMID- 16422574
TI  - Statistical mechanics of quantum-classical systems with holonomic constraints.
AB  - The statistical mechanics of quantum-classical systems with holonomic constraints
      is formulated rigorously by unifying the classical Dirac bracket and the quantum
      classical bracket in matrix form. The resulting Dirac quantum-classical theory,
      which conserves the holonomic constraints exactly, is then used to formulate time
      evolution and statistical mechanics. The correct momentum-jump approximation for
      constrained systems arises naturally from this formalism. Finally, in analogy
      with what was found in the classical case, it is shown that the rigorous linear
      response function of constrained quantum-classical systems contains nontrivial
      additional terms which are absent in the response of unconstrained systems.

PMID- 16422575
TI  - Distributed polarizabilities obtained using a constrained density-fitting
      algorithm.
AB  - A computationally efficient method for obtaining distributed polarizabilities of
      arbitrary rank using a constrained density-fitting algorithm is demonstrated on
      the hydrogen, carbon dioxide, formamide, and N-methylpropanamide molecules. A
      description of the molecular polarization in terms of local polarizabilities
      without charge-flow terms is obtained when the nonlocal components of the
      polarizability tensor are transformed away using the localization method of Le
      Sueur and Stone [Mol. Phys. 83, 293 (1994)]. The resulting local polarizabilities
      are shown to be stable with respect to basis set used, exhibiting none of the
      artifacts of earlier basis-space partitioning methods. We also investigate the
      transferability of the resulting local polarizability models.

PMID- 16422576
TI  - Kramers escape rate in nonlinear diffusive media.
AB  - In this paper, we study nonlinear Kramers problem by investigating overdamped
      systems ruled by the one-dimensional nonlinear Fokker-Planck equation. We obtain
      an analytic expression for the Kramers escape rate under quasistationary
      conditions by employing a metastable potential and its predictions are in
      excellent agreement with numerical simulations. The results exhibit the anomalies
      due to the nonlinearity in W that the escape rate grows with D and drops as mu
      becomes large at a fixed D. Indeed, particles in the subdiffusive media (mu>1)
      can escape over the barrier only when D is above a critical value, while this
      confinement does not exist in the superdiffusive media (mu<1).

PMID- 16422578
TI  - IR+vacuum ultraviolet (118 nm) nonresonant ionization spectroscopy of methanol
      monomers and clusters: neutral cluster distribution and size-specific detection
      of the OH stretch vibrations.
AB  - Small methanol clusters are formed by expanding a mixture of methanol vapor
      seeded in helium and are detected using vacuum UV (vuv) (118 nm) single-photon
      ionization/linear time-of-flight mass spectrometer (TOFMS). Protonated cluster
      ions, (CH3OH)(n-1)H+ (n=2-8), formed through intracluster ion-molecule reactions
      following ionization, essentially correlate to the neutral clusters, (CH3OH)n, in
      the present study using 118 nm light as the ionization source. Both experimental
      and Born-Haber calculational results clarify that not enough excess energy is
      released into protonated cluster ions to initiate further fragmentation in the
      time scale appropriate for linear TOFMS. Size-specific spectra for (CH3OH)n (n=4
      to 8) clusters in the OH stretch fundamental region are recorded by IR+vuv (118
      nm) nonresonant ion-dip spectroscopy through the detection chain of IR
      multiphoton predissociation and subsequent vuv single-photon ionization. The
      general structures and gross features of these cluster spectra are consistent
      with previous theoretical calculations. The lowest-energy peak contributed to
      each cluster spectrum is redshifted with increasing cluster size from n=4 to 8,
      and limits near approximately 3220 cm(-1) in the heptamer and octamer. Moreover,
      IR+vuv nonresonant ionization detected spectroscopy is employed to study the OH
      stretch first overtone of the methanol monomer. The rotational temperature of the
      clusters is estimated to be at least 50 K based on the simulation of the monomer
      rotational envelope under clustering conditions.

PMID- 16422577
TI  - Density-functional geometry optimization of the 150,000-atom photosystem-I
      trimer.
AB  - We present a linear-scaling method based on the use of density-functional theory
      (DFT) for the system-wide optimization of x-ray structural coordinates and apply
      it to optimize the 150,000 atoms of the photosystem-I (PS-I) trimer. The method
      is based on repetitive applications of a multilevel ONIOM procedure using the
      PW916-31G(d) DFT calculations for the high level and PM3 for the lower level;
      this method treats all atoms in the structure equivalently, a structure in which
      the majority of the atoms can be considered as part of some internal "active
      site." To obtain a realistic single structure, some changes to the original
      protein model were necessary but these are kept to a minimum in order that the
      optimized structure most closely resembles the original x-ray one. Optimization
      has profound effects on the perceived electronic properties of the cofactors,
      with, e.g., optimization lowering the internal energy of the chlorophylls by on
      average 53 kcal mol(-1) and eliminates the enormous 115 kcal mol(-1) energy
      spread depicted by the original x-ray heavy-atom coordinates. A highly precise
      structure for PS-I results that is suitable for analysis of device function.
      Significant qualitative features of the structure are also improved such as
      correction of an error in the stereochemistry of one of the chlorophylls in the
      "special pair" of the reaction center, as well as the replacement of a water
      molecule with a metal cation in a critical region on the C3 axis. The method also
      reveals other unusual features of the structure, leading both to suggestions
      concerning device functionality and possible mutations between gene sequencing
      and x-ray structure determination. The optimization scheme is thus shown to
      augment the molecular modeling schemes that are currently used to add medium
      resolution structural information to the raw scattering data in order to obtain
      atomically resolved structures. System-wide optimization is now a feasible
      process and its use within protein x-ray data refinement should be considered.

PMID- 16422579
TI  - Postcollision relaxation of small atomic clusters.
AB  - Molecular-dynamics simulations are performed to investigate the effects caused by
      the lack of internal equilibration on the dynamics and properties of atomic
      clusters. The studied systems consist of Lennard-Jones clusters of five to ten
      atoms and a colliding vapor monomer. Cluster radius and potential energy are
      shown to reach a time-independent value within 30 ps after a collision with a
      vapor monomer. The relaxation in terms of rotational energy takes at least 200
      ps. During the first couple of picoseconds after the collision time-dependent
      cluster decay rates are observed. The unrelaxed cluster states are expected to
      have minimal effect on gas-liquid nucleation rates.

PMID- 16422580
TI  - Reaction dynamics of Ca(4s3d 1D2)+CH4-->CaH(X 2Sigma+)+CH3: reaction pathway and
      energy disposal for the CaH product.
AB  - The reaction pathway for Ca(4s3d 1D2)+CH4-->CaH(X 2Sigma+)+CH3 has been
      investigated by using a pump-probe technique in combination with potential-energy
      surface (PES) calculations. The nascent product distributions of CaH have been
      characterized with Boltzmann rotational temperatures of 1013+/-102 and 834+/-70 K
      for the v=0 and 1 levels, respectively, and a Boltzmann vibrational temperature
      of 1313+/-173 K. The rotational and vibrational energy partitions in CaH have
      been estimated to be 461+/-45 and 252+/-15 cm(-1), respectively. According to the
      PES calculations, the pathway favors an insertion mechanism. Ca(3 1D2) approaches
      CH4 along an attractive potential surface in a C2v (or Cs) symmetry and then the
      collision complex undergoes nonadiabatic transition to the reactive ground-state
      surface. An Arrhenius plot shows a potential-energy requirement of 2695+/-149 cm(
      1), which accounts for the endothermicity of 2930 cm(-1) for the reaction scheme.
      The Ca-C bond distance in the transition state structure is short enough to allow
      for tight orbital overlap between CaH and CH3. The strong coupling between the
      moieties renders the energy transfer sufficient from CaH into the CH3 radical. As
      compared to the Ca(4 1P1) reaction, the dissociation lifetime of the intermediate
      complex with less excess energy is prolonged so as to cause much less vibrational
      energy disposal into CaH.

PMID- 16422581
TI  - Dynamics of OH radical generation in laser-induced photodissociation of
      tetrahydropyran at 193 nm.
AB  - Tetrahydropyran (THP) undergoes photodissociation on excitation with ArF laser at
      193 nm, generating OH radical as one of the transient photoproducts. Laser
      induced fluorescence technique is used to detect the nascent OH radical and
      measure its energy state distribution. The OH radical is formed mostly in the
      ground vibrational level (v"=0), with low rotational excitation. The rotational
      distribution of OH (v"=0,J) is characterized by a temperature of 433+/-31 K,
      corresponding to a rotational energy of 0.86+/-0.06 kcalmol. Two Lambda-doublet
      levels, 2Pi+(A') and 2Pi-(A"), and the two spin-orbit states, the 2Pi(3/2) and
      2Pi(1/2), of OH are populated statistically for all rotational levels. The
      relative translational energy associated with the photoproducts in the OH channel
      is calculated to be 21.9+/-3.2 kcal mol(-1), from the Doppler-broadened
      linewidth, giving an ft value of approximately 43%, and most of the remaining 57%
      of the available energy is distributed in the internal modes of the other
      photofragment, C5H9. The observed distribution of the available energy is
      explained well, using a hybrid model of energy partitioning, with an exit barrier
      of 40 kcal mol(-1). The potential-energy surface of the reaction channel was
      mapped by ab initio molecular-orbital calculations. Based on experimental and
      theoretical results, a mechanism for OH formation is proposed. Electronically
      excited THP relaxes to the ground electronic state, and from there, a sequence of
      reactions takes place, generating OH. The proposed mechanism first involves C-O
      bond scission, followed by a 1,3 H atom migration to O atom, and finally, the C
      OH bond cleavage giving OH.

PMID- 16422582
TI  - On the theory of the reaction rate of vibrationally excited CO molecules with OH
      radicals.
AB  - The dependence of the rate of the reaction CO+OH-->H+CO2 on the CO-vibrational
      excitation is treated here theoretically. Both the Rice-Ramsperger-Kassel-Marcus
      (RRKM) rate constant kRRKM and a nonstatistical modification knon [W.-C. Chen and
      R. A. Marcus, J. Chem. Phys. 123, 094307 (2005).] are used in the analysis. The
      experimentally measured rate constant shows an apparent (large error bars)
      decrease with increasing CO-vibrational temperature Tv over the range of Tv's
      studied, 298-1800 K. Both kRRKM(Tv) and knon(Tv) show the same trend over the Tv
      range studied, but the knon(Tv) vs Tv plot shows a larger effect. The various
      trends can be understood in simple terms. The calculated rate constant kv
      decreases with increasing CO vibrational quantum number v, on going from v=0 to
      v=1, by factors of 1.5 and 3 in the RRKM and nonstatistical calculations,
      respectively. It then increases when v is increased further. These results can be
      regarded as a prediction when v state-selected rate constants become available.

PMID- 16422583
TI  - Line positions and line strengths for the 3<--0 electric quadrupole band of H2
      1Sigmag +.
AB  - Several rotational lines in the S and Q branches [including the previously
      unobserved Q(2) and Q(3) lines] of the 3-0 electric quadrupole band of H2 have
      been detected by cavity ring-down spectroscopy. Line strengths were measured at
      densities between 2.7x10(18) and 7.5x10(19) molecules cm-3 at room temperature.
      The observed line strengths in the S branch are consistent with earlier
      measurements, and systematically below theoretical calculations [relative
      differences of approximately 10% for the S(1),S(2), and S(3) lines, and nearly
      30% for the S(0) line]. Line strength measurements for the Q branch range from
      25% to 33% below theoretical calculations.

PMID- 16422584
TI  - Structure and shape variations in intermediate-size copper clusters.
AB  - Using extensive, unbiased searches based on density-functional theory, we explore
      the structural evolution of Cu(n) clusters over the size range n=8-20. For n=8
      16, the optimal structures are plateletlike, consisting of two layers, with the
      atoms in each layer forming a trigonal bonding network similar to that found in
      smaller, planar clusters (n<or=6). For n=17 and beyond, there is a transition to
      compact structures containing an icosahedral 13-atom core. The calculated ground
      state structures are significantly different from those predicted earlier in
      studies based on empirical and semiempirical potentials. The evolution of the
      structure and shape of the preferred configuration of Cu(n), n<or=20, is shown to
      be nearly identical to that found for Na clusters, indicating a shell-model-type
      behavior in this size range.

PMID- 16422585
TI  - The permanent electric dipole moment and hyperfine interaction in ruthenium
      monoflouride (RuF).
AB  - Ruthenium monofluoride, RuF, has been detected using low-resolution laser-induced
      fluorescence (LIF) in the visible and near infrared spectral regions. A visible
      band, designated as [18.2]5.5-X 4Phi(9/2), has been recorded field-free and in
      the presence of a static electric field using high-resolution LIF spectroscopy.
      The r0 internuclear distances for the [18.2]5.5 and X 4Phi(9/2) states were
      determined to be 1.911 and 1.916 A, respectively. The vibrational interval
      DeltaG(1/2) of 534(15) cm-1 for the X 4Phi(9/2) state was determined from the
      analysis of the dispersed LIF. The Stark shifts of the visible band were analyzed
      to produce permanent electric dipole moments of 1.97(8) and 5.34(7) D for the
      [18.2]5.5 and X 4Phi(9/2), states, respectively. The fluorine magnetic hyperfine
      structure associated with spectral features was analyzed. The hyperfine structure
      and dipole moments are interpreted using a molecular-orbital correlation model
      and compared with FeF and other ruthenium-containing molecules.

PMID- 16422586
TI  - Lifetimes of C60(2-) and C70(2-) dianions in a storage ring.
AB  - C60(2-) and C70(2-) dianions have been produced by electrospray of the monoanions
      and subsequent electron pickup in a Na vapor cell. The dianions were stored in an
      electrostatic ring and their decay by electron emission was measured up to 1 s
      after injection. While C70(2-) ions are stable on this time scale, except for a
      small fraction of the ions which have been excited by gas collisions, most of the
      C60(2-) ions decay on a millisecond time scale, with a lifetime depending
      strongly on their internal temperature. The results can be modeled as decay by
      electron tunneling through a Coulomb barrier, mainly from thermally populated
      triplet states about 120 meV above a singlet ground state. At times longer than
      about 100 ms, the absorption of blackbody radiation plays an important role for
      the decay of initially cold ions. The tunneling rates obtained from the modeling,
      combined with WKB estimates of the barrier penetration, give a ground-state
      energy 200+/-30 meV above the energy of the monoanion plus a free electron and a
      ground-state lifetime of the order of 20 s.

PMID- 16422587
TI  - High-resolution infrared spectroscopy and ab initio studies of the cyclopropane
      carbon dioxide interaction.
AB  - A jet-cooled high-resolution infrared spectrum of the cyclopropane-carbon dioxide
      complex was detected for the first time, using a rapid scan infrared spectrometer
      with an astigmatic multipass sample cell. The spectrum was recorded in the
      vicinity of the CO2 asymmetric stretching band (nu3) and exhibits a b-dipole
      selection rule. Altogether, over 200 lines were observed, assigned, and fitted to
      Watson's S-reduction Hamiltonian. Rotational and quartic distortion constants
      were obtained. The band origin was located at 2347.6263(2) cm(-1), redshifted by
      1.5230(2) cm(-1) from the corresponding frequency of the CO2 monomer. The
      experimentally determined structure shows that CO2 lies next to a C-C bond edge
      and is perpendicular to the C3 ring, indicating that the interaction is
      characterized by the bonding between the carbon atom of CO2 and the pseudo-pi
      system of cyclopropane. The intermolecular distance between the carbon atom of
      CO2 and the center of mass of cyclopropane was determined to be 3.667(2) A.
      Complete ab initio geometry optimizations and harmonic frequency calculations
      were carried out at the level of second-order Moller-Plesset perturbation theory
      with four different basis sets: cc-pVDZ, 6-311++G(d,p), aug-cc-pVDZ, and aug-cc
      pVTZ. The lowest-energy structure identified with the three larger basis sets is
      in accord with the experimental finding. In addition, a transition state was
      identified and the tunneling barrier height was computed.

PMID- 16422588
TI  - Two-state versus three-state quantization: an ab initio study of the three lower
      states of the {N,H2/A'} system.
AB  - In this article we present the first ab initio study of the conical intersections
      (cis) and their electronic nonadiabatic coupling terms (NACTs) for the {N,H2}
      system. Efforts were made to reveal the location of cis between the two lower, 1
      2A' and 2 2A' states--to be designated as (1,2) cis--and the cis between the two
      upper, 2 2A' and 3 2A' states--to be designated as the (2,3) cis--of this system.
      We found that these cis are located along the collinear {NHH) arrangement. The
      study is carried out by analyzing two-state magnitudes such as the (1,2) and
      (2,3) adiabatic-to-diabatic transformation angles (known also as the mixing
      angles) and the corresponding topological phases (known also as the Berry phases
      or the Longuet-Higgins phases). In addition, a detailed three-state study is
      carried out. Here the emphasis is on driving the diagonal elements of the
      topological D matrix and analyzing situations for which the corresponding
      nonadiabatic coupling matrix is quantized. The reliability of two-state results
      is carefully examined by comparing them with corresponding outcomes derived for
      the three-state study. In addition we also calculated the potential-energy
      surfaces related to the two lower states and studied to what extent they are
      affected by the (1,2) ci. The results obtained in this treatment were found to be
      in full agreement with the NACT's calculations.

PMID- 16422589
TI  - Cesium dimer spectroscopy on helium droplets.
AB  - Visible absorption spectra of cesium-doped helium nanodroplets between 14,500 and
      17,600 cm(-1) were probed by laser-induced fluorescence. A strong absorption band
      peaking around 16,700 cm(-1) is identified as Cs2 1(a) 3Sigmau+-3 3Sigmag+
      transition. A broad unstructured band near 17,520 cm(-1) is assigned as the Cs2
      1(X) 1Sigmag+-2 1Sigmau+ transition. Explanations of the observations are
      discussed on the basis of ab initio potential curves calculated by Spies and
      Meyer [(unpublished)]. All spectra have been modeled using narrow Frank-Condon
      windows around the equilibrium internuclear distance of the lowest singlet and
      triplet states. Many observed absorption peaks of smaller intensities could be
      identified, some of which may be due to transitions of cesium trimers formed on
      the droplets.

PMID- 16422590
TI  - Vibronic coupling in cyclopentadienyl radical: a method for calculation of
      vibronic coupling constant and vibronic coupling density analysis.
AB  - A method of calculation of vibronic or electron-phonon coupling constant is
      presented for a Jahn-Teller molecule, cyclopentadienyl radical. It is pointed out
      that symmetry breaking at degenerate point and violation of Hellmann-Feynman
      theorem occur in the calculations based on a single Slater determinant. In order
      to overcome these difficulties, the electronic wave functions are calculated
      using generalized restricted Hartree-Fock and complete active space self
      consistent-field method and the couplings are computed as matrix elements of the
      electronic operator of the vibronic coupling. Our result agrees well with the
      experimental and theoretical values. A concept of vibronic coupling density is
      proposed in order to explain the order of magnitude of the coupling constant from
      view of the electronic and vibrational structures. It illustrates the local
      properties of the coupling and enables us to control the interaction. It could
      open a way to the engineering of vibronic interactions.

PMID- 16422592
TI  - Structure of Au8: planar or nonplanar?
AB  - We have studied the structures and stabilities of Au6 and Au8 at the density
      functional theory (DFT) and ab initio correlated levels of theory. For Au8, our
      ab initio calculations predict the lowest Au8 isomer to be planar, in line with
      the DFT calculations.

PMID- 16422591
TI  - Photofragment alignment in the photodissociation of I2 from 450 to 510 nm.
AB  - A combination of velocity map imaging and slicing techniques have been used to
      measure the product recoil anisotropy and angular momentum polarization for the
      photodissociation process I2-->I(2P(3/2))+I(2P(3/2)) and I2-
      >I(2P(3/2)))+I(2P(1/2)) in the 450-510 nm laser wavelength region using linearly
      polarized photolysis and probe laser light. The former channel is produced
      predominantly via perpendicular excitation to the 1Piu state, and the latter is
      predominantly parallel, via the B 3Pi(0u)+ state. In both cases we observe mostly
      adiabatic dissociation, which produces electronically aligned iodine atoms in the
      mid /m/=1/2 states with respect to the recoil direction.

PMID- 16422593
TI  - Molecular vibrational energy flow and dilution factors in an anharmonic state
      space.
AB  - A fourth-order resonance Hamiltonian is derived from the experimental normal-mode
      Hamiltonian of SCCl2. The anharmonic vibrational state space constructed from the
      effective Hamiltonian provides a realistic model for vibrational energy flow from
      bright states accessible by pulsed laser excitation. We study the experimentally
      derived distribution PE(sigma) of dilution factors sigma as a function of energy.
      This distribution characterizes the dynamics in the long-time limit. State space
      models predict that PE(sigma) should be bimodal, with some states undergoing
      facile intramolecular vibrational energy redistribution (small sigma), while
      others at the same total energy remain "protected" (sigma approximately 1). The
      bimodal distribution is in qualitative agreement with analytical and numerical
      local density of states models. However, there are fewer states protected from
      energy flow, and the protected states begin to fragment at higher energy,
      shifting from sigma approximately 1 to sigma approximately 0.5. We also examine
      how dilution factors are distributed in the vibrational state space of SCCl2 and
      how the power law specifying the survival probability of harmonic initial states
      correlates with the dilution factor distribution of anharmonic initial states.

PMID- 16422594
TI  - Quantum Monte Carlo calculations of the dissociation energies of three-electron
      hemibonded radical cationic dimers.
AB  - We report variational and diffusion quantum Monte Carlo (VMC and DMC)
      calculations of the dissociation energies of the three-electron hemibonded
      radical cationic dimers of He, NH3, H2O, HF, and Ne. These systems are
      particularly difficult for standard density-functional methods such as the local
      density approximation and the generalized gradient approximation. We have
      performed both all-electron (AE) and pseudopotential (PP) calculations using
      Slater-Jastrow wave functions with Hartree-Fock single-particle orbitals. Our
      results are in good agreement with coupled-cluster CCSD(T) calculations. We have
      also studied the relative stability of the hemibonded and hydrogen-bonded water
      radical dimer isomers. Our calculations indicate that the latter isomer is more
      stable, in agreement with post-Hartree-Fock methods. The excellent agreement
      between our AE and PP results demonstrates the high quality of the PPs used
      within our VMC and DMC calculations.

PMID- 16422595
TI  - Mimicking solvent shells in the gas phase. II. Solvation of K+.
AB  - The observed gas-phase coordination number of K+ in K+(H2O)m clusters is smaller
      than that observed in bulk solution, where the coordination number has been
      reported to be between 6 and 8. Both theoretical and gas-phase studies of
      K+(H2O)m cluster ions point to a coordination number closer to 4. In the gas
      phase, the coordination number is determined by a variety of factors-the most
      critical being the magnitude of the K+...ligand pairwise interaction. Decreasing
      the magnitude of the ion...ligand interaction allows more ligands to directly
      interact with the cation. One method for decreasing the ion...ligand interaction
      in K+(H2O)m clusters is to systematically substitute weakly bound ligands for the
      more strongly bound water molecules. The systematic introduction of para
      difluorobenzene (DFB) to K+(H2O)m clusters was monitored using infrared
      photodissociation spectroscopy in the OH stretching region. By varying the ratio
      of DFB molecules to water molecules present in K+(H2O)m(DFB)n clusters, the
      observed coordination number of gas-phase K+ was increased to 8, similar to that
      reported for bulk solution.

PMID- 16422596
TI  - Analysis of adiabatic passage by light-induced potentials with chirped laser
      pulses in three- and four-level diatomic systems.
AB  - This paper describes an investigation into the process of adiabatic passage by
      light-induced potentials (APLIP), which was previously suggested as a method for
      employing two strong picosecond laser pulses to transfer the population between
      two electronic states. We have extended earlier numerical studies in order to
      assess the feasibility of an experimental implementation of the APLIP concept.
      APLIP has been modeled in a three-level model system based on Na2 with chirped
      pulses, using laser parameters available from a typical chirped pulse amplified
      Ti:sapphire laser. The model showed that the APLIP process remains essentially
      unchanged for chirped pulses of equal magnitude and the opposite, or equal and
      positive sign of chirp as compared to the transform-limited case. We also
      examined the case of additional electronic states by introduction of a fourth
      state that lies close to the "target," i.e., final, state. The investigation
      showed that there are circumstances in which a significant fraction of the
      population gets transferred to this state which will disrupt the APLIP process.
      However, by switching to this fourth state as the target state in an experiment,
      good transfer efficiency is recovered. The results of the extension of the
      original APLIP modeling to chirped pulses and additional electronic states
      indicate that an APLIP experimental realization should be feasible in Na2.

PMID- 16422597
TI  - Ab initio study of hydrated sodium halides NaX(H2O)(1-6) (X=F, Cl, Br, and I).
AB  - We have studied the dissociation phenomena of sodium halides by water molecules.
      The structures, binding energies, electronic properties, and IR spectroscopic
      features have been investigated by using the density-functional theory, second
      order Moller-Plesset perturbation theory, and coupled clusters theory with
      single, double, and perturbative triplet excitations. In the case that the sodium
      halides are hydrated by three water molecules, the most stable structures show
      the partial (or half) dissociation feature. The dissociated structures are first
      found for NaX(H2O)(n=5) for X=BrI, though these structures are slightly higher in
      energy than the global minimum-energy structure. In the case of hexahydrated
      sodium halides the global minimum-energy structures (which are different from the
      structures reported in any previous work) are found to be dissociated (X=F/I) or
      partially/half dissociated (X=Cl/Br), while other nearly isoenergetic structures
      are undissociated, and the dissociated cubical structures are higher in energy
      than the corresponding global minimum-energy structure.

PMID- 16422598
TI  - A comparative ab initio study of Br2*- and Br2 water clusters.
AB  - The work presents ab initio results on structure and electronic properties of
      Br2*-.nH2O(n=1-10) and Br2.nH2O(n=1-8) hydrated clusters to study the effects of
      an excess electron on the microhydration of the halide dimer. A nonlocal density
      functional, namely, Becke's half-and-half hybrid exchange-correlation functional
      is found to perform well on the present systems with a split valence 6-31++G(d,p)
      basis function. Geometry optimizations for all the clusters are carried out with
      several initial guess structures and without imposing any symmetry restriction.
      Br2*-.nH2O clusters prefer to have symmetrical double hydrogen-bonding
      structures. Results on Br2.nH2O(n>or=2) cluster show that the O atom of one H2O
      is oriented towards one Br atom and the H atom of another H2O is directed to
      other Br atom making Br2 to exist as Br+-Br- entity in the cluster. The binding
      and solvation energies are calculated for the Br2*-.nH2O and Br2.nH2O clusters.
      Calculations of the vibrational frequencies show that the formation of Br2*- and
      Br2 water clusters induces significant shifts from the normal modes of isolated
      water. Excited-state calculations are carried out on Br2*-.nH2O clusters
      following configuration interaction with single electron excitation procedure and
      UV-VIS absorption profiles are simulated. There is an excellent agreement between
      the present theoretical UV-VIS spectra of Br2*-.10H2O cluster and the reported
      transient optical spectra for Br2*- in aqueous solution.

PMID- 16422599
TI  - Experimental and theoretical elastic cross sections for electron collisions with
      the C3H6 isomers.
AB  - In the present work we report cross sections for electron collisions with the
      isomers propene (C3H6) and cyclopropane (c-C3H6). Electron-scattering
      differential cross sections (DCS) are reported for measurements carried out for
      energies 1.5-100 eV and the angular range of 20 degrees-120 degrees. Elastic
      integral cross sections (ECS), DCS, and momentum-transfer cross sections (MTCS)
      are reported for calculations carried out using the Schwinger multichannel method
      with pseudopotentials for the energy range of 2.0-40 eV and angular range of 0
      degrees-180 degrees. The resemblance of the pi* shape resonance in the cross
      sections, observed at 1.5-2.0 eV for propene, to those in C2H4 and C2F4 clearly
      points to the effect of the double bond in the molecular structures for these
      molecules. Below 60 eV, we observed clear differences in peak positions and
      magnitudes between the DCS, ECS, and MTCS for C3H6 and c-C3H6, which we view as
      the isomer effect.

PMID- 16422600
TI  - Photodissociation dynamics of ketene at 157.6 nm.
AB  - Photodissociation dynamics of ketene at 157.6 nm has been investigated using the
      photofragment translational spectroscopic technique based on photoionization
      detection using vacuum-ultraviolet synchrotron radiation. Three dissociation
      channels have been observed: CH2+CO, CH+HCO, and HCCO+H. The product
      translational energy distributions and angular anisotropy parameters were
      measured for all three observed dissociation channels, and the relative branching
      ratios for different channels were also estimated. The experimental results show
      that the direct C-C bond cleavage (CH2+CO) is the dominant channel, while H
      migration and elimination channels are very minor. The results in this work show
      that direct dissociation on excited electronic state is much more significant
      than the indirect dissociation via the ground state in the ketene
      photodissociation at 157.6 nm.

PMID- 16422601
TI  - Geometrical and electronic properties of neutral and charged cesium clusters
      Cs(n) (n=2-10): a theoretical study.
AB  - We have investigated the structure and electronic properties of cesium clusters
      following all electron ab initio theoretical methods based on configuration
      interaction, second-order Moller-Plesset (MP2) perturbation theory, and density
      functional theory. Becke's three-parameter nonlocal hybrid exchange-correlation
      functional (B3LYP) is found to perform best on the present systems with a split
      valence 3-21G basis function. We have calculated the optimized geometries of
      neutral and singly charged cesium clusters having up to ten atoms, their binding
      energy per atom, ionization potentials (IPs), and adiabatic electron affinity
      (EA). Geometry optimizations for all the clusters are carried out without
      imposing any symmetry restriction. The neutral clusters having up to six atoms
      prefer planar structure and three-dimensional structure is preferred only when
      the number of atoms in a cluster is more than six. There is a good agreement
      between the present theoretical and reported experimental IP values for the
      neutral clusters with cluster size n<or=10. Calculated EA is also in good
      agreement with the available experimental data for the small Cs clusters. Similar
      calculations have also been carried out for small Rb clusters and the performance
      of B3LYP is equally good. Thermodynamic properties such as enthalpy and entropy
      for small Cs and Rb clusters have also been calculated and are well compared with
      the experimental data.

PMID- 16422602
TI  - Theoretical study on the circular dichroism in core and valence photoelectron
      angular distributions of camphor enantiomers.
AB  - In the present work the photoelectron circular dichroism of camphor has been
      theoretically studied using B-spline and continuum multiple scattering-Xalpha
      methods, and comparisons are made with available experimental data. In general,
      rather large dichroism effects have been found for both valence and core (O 1s, C
      1s) photoionizations. The agreement between the two calculations reported here
      and previous experimental measurements for core C 1s data is essentially
      quantitative. For valence ionization satisfactory agreement between theory and
      experiment has been obtained and the discrepancies have been attributed to both
      exchange-correlation potential limitations and the absence of response effects in
      the adopted formalism. The calculations predict, moreover, important features in
      the cross-section profiles, which have been discussed in terms of dipole-prepared
      continuum orbitals.

PMID- 16422603
TI  - The properties of ion-water clusters. II. Solvation structures of Na+, Cl-, and
      H+ clusters as a function of temperature.
AB  - Ion-water-cluster properties are investigated both through the multistate
      empirical valence bond potential and a polarizable model. Equilibrium properties
      of the ion-water clusters H+(H2O)100, Na+(H2O)100, Na+(H2O)20, and Cl-(H2O)17 in
      the temperature region 100-450 K are explored using a hybrid parallel basin
      hopping and tempering algorithm. The effect of the solid-liquid phase transition
      in both caloric curves and structural distribution functions is investigated. It
      is found that sodium and chloride ions largely reside on the surface of water
      clusters below the cluster melting temperature but are solvated into the interior
      of the cluster above the melting temperature, while the solvated proton was found
      to have significant propensity to reside on or near the surface in both the
      liquid- and solid-state clusters.

PMID- 16422604
TI  - Fragmentation dynamics of ionized neon clusters (Ne(n), n=3-14) embedded in
      helium nanodroplets.
AB  - We report a theoretical study of the nonadiabatic fragmentation dynamics of
      ionized neon clusters embedded in helium nanodroplets for cluster sizes up to
      n=14 atoms. The dynamics of the neon atoms is modeled using the molecular
      dynamics with quantum transitions method of Tully [J. Chem. Phys. 93, 1061
      (1990)] with the nuclei treated classically and transitions between electronic
      states quantum mechanically. The potential-energy surfaces are derived from a
      diatomics-in-molecules model to which induced dipole-induced dipole interactions
      are added. The effect of the spin-orbit interaction is also discussed. The helium
      environment is modeled by a friction force acting on charged atoms whose speed
      exceeds the critical Landau velocity. The dependence of the fragment size
      distribution on the friction strength and on the initial nanodroplet size is
      investigated. By comparing with the available experimental data obtained for Ne3+
      and Ne4+, a reasonable value for the friction coefficient, the only parameter of
      the model, is deduced. This value is then used to predict the effect of the
      helium environment on the dissociation dynamics of larger neon clusters, n=5-14.
      The results show stabilization of larger fragments than in the gas phase, but
      fragmentation is not completely caged. In addition, two types of dynamics are
      characterized for Ne4+: fast and explosive, therefore leaving no time for
      friction to cool down the process when dynamics starts on one of the highest
      electronic states, and slower, therefore leading to some stabilization by helium
      when it starts on one of the lowest electronic states.

PMID- 16422605
TI  - Proton dynamics in lithium-ammonia solutions and expanded metals.
AB  - Quasielastic neutron scattering has been used to study proton dynamics in the
      system lithium-ammonia at concentrations of 0, 4, 12, and 20 mole percent metal
      (MPM) in both the liquid and solid (expanded metal) phases. At 230 K, in the
      homogenous liquid state, we find that the proton self-diffusion coefficient first
      increases with metal concentration, from 5.6x10(-5) cm2 s(-1) in pure ammonia to
      7.8x10(-5) cm2 s(-1) at 12 MPM. At higher concentrations we note a small decrease
      to a value of 7.0x10(-5) cm2 s(-1) at 20 MPM (saturation). These results are
      consistent with NMR data, and can be explained in terms of the competing
      influences of the electron and ion solvation. At saturation, the solution freezes
      to form a series of expanded metal compounds of composition Li(NH3)4. Above the
      melting point, at 100 K, we are able to fit our data to a jump-diffusion model,
      with a mean jump length (l) of 2.1 A and residence time (tau) of 3.1 ps. This
      model gives a diffusion coefficient of 2.3x10(-5) cm2 s(-1). In solid phase I
      (cubic, stable from 88.8 to 82.2 K) we find that the protons are still undergoing
      this jump diffusion, with l=2.0 A and tau=3.9 ps giving a diffusion coefficient
      of 1.8x10(-5) cm2 s(-1). Such motion gives way to purely localized rotation in
      solid phases IIa (from 82.2 to 69 K) and IIb (stable from 69 to 25 K). We find
      rotational correlation times (tau(rot)) of the order of 2.0 and 7.3 ps in phases
      IIa and IIb, respectively. These values can be compared with a rotational mode in
      solid ammonia with tau(rot) approximately 2.4 ps at 150 K.

PMID- 16422606
TI  - High-pressure x-ray diffraction and Raman spectroscopy of ice VIII.
AB  - In situ high-pressure/low-temperature synchrotron x-ray diffraction and optical
      Raman spectroscopy were used to examine the structural properties, equation of
      state, and vibrational dynamics of ice VIII. The x-ray measurements show that the
      pressure-volume relations remain smooth up to 23 GPa at 80 K. Although there is
      no evidence for structural changes to at least 14 GPa, the unit-cell axial ratio
      ca undergoes changes at 10-14 GPa. Raman measurements carried out at 80 K show
      that the nu(Tz)A(1g)+nuT(x,y)E(g) lattice modes for the Raman spectra of ice VIII
      in the lower-frequency regions (50-800 cm(-1)) disappear at around 10 GPa, and
      then a new peak of approximately 150 cm(-1) appears at 14 GPa. The combined data
      provide evidence for a transition beginning near 10 GPa. The results are
      consistent with recent synchrotron far-IR measurements and theoretical
      calculations. The decompressed phase recovered at ambient pressure transforms to
      low-density amorphous ice when heated to approximately 125 K.

PMID- 16422608
TI  - A simple model for the water o-H2 complex.
AB  - The infrared spectrum of the complex between o-H2 and H2O, D2O, or HDO, isolated
      in a matrix of solid p-H2, has been studied between 20 and 4500 cm(-1). In
      addition the infrared spectrum of the complex between p-D2 and H2O in solid o-D2
      has been studied. The spectral shifts are interpreted as the result of the
      quadrupole-dipole interaction between hydrogen and water.

PMID- 16422607
TI  - Flexible simple point-charge water model with improved liquid-state properties.
AB  - In order to introduce flexibility into the simple point-charge (SPC) water model,
      the impact of the intramolecular degrees of freedom on liquid properties was
      systematically studied in this work as a function of many possible parameter
      sets. It was found that the diffusion constant is extremely sensitive to the
      equilibrium bond length and that this effect is mainly due to the strength of
      intermolecular hydrogen bonds. The static dielectric constant was found to be
      very sensitive to the equilibrium bond angle via the distribution of
      intermolecular angles in the liquid: A larger bond angle will increase the angle
      formed by two molecular dipoles, which is particularly significant for the first
      solvation shell. This result is in agreement with the work of Hochtl et al. [J.
      Chem. Phys. 109, 4927 (1998)]. A new flexible simple point-charge water model was
      derived by optimizing bulk diffusion and dielectric constants to the experimental
      values via the equilibrium bond length and angle. Due to the large sensitivities,
      the parametrization only slightly perturbs the molecular geometry of the base SPC
      model. Extensive comparisons of thermodynamic, structural, and kinetic properties
      indicate that the new model is much improved over the standard SPC model and its
      overall performance is comparable to or even better than the extended SPC model.

PMID- 16422609
TI  - Cage motions induced by electronic and vibrational excitations: Cl2 in Ar.
AB  - Femtosecond dynamics of molecular vibrations as well as cage motions in the B<--X
      transition of Cl2 in solid Ar have been investigated. We observed molecular
      vibrational wave-packet motion in experimental pump-probe spectra and an
      additional oscillation with a 500 fs period which is assigned to the zone
      boundary phonon of the Ar crystal. The cage motion is impulsively driven by the
      B<--X transition due to the expansion of the electronic cloud of the chromophore.
      To clarify the underlying mechanism, we performed simulations based on the
      diatomics-in-molecules method which takes into account the different shapes of
      the Cl2 electronic wave function in the B and X states as well as the anisotropic
      interaction with the matrix. The simulation results show that Ar atom motion in
      the (100) plane is initiated by the electronic transition and that only those Ar
      atoms oscillate coherently with an approximately 500 fs period which are
      essentially decoupled from the molecular vibration. Their phase and time
      evolution are in good agreement with the experimentally observed oscillation,
      supporting the assignment as a displacive excitation of coherent phonons.

PMID- 16422610
TI  - Temperature- and solvation-dependent dynamics of liquid sulfur dioxide studied
      through the ultrafast optical Kerr effect.
AB  - The ultrafast dynamics of liquid sulphur dioxide have been studied over a wide
      temperature range and in solution. The optically heterodyne-detected and
      spatially masked optical Kerr effect (OKE) has been used to record the
      anisotropic and isotropic third-order responses, respectively. Analysis of the
      anisotropic response reveals two components, an ultrafast nonexponential
      relaxation and a slower exponential relaxation. The slower component is well
      described by the Stokes-Einstein-Debye equation for diffusive orientational
      relaxation. The simple form of the temperature dependence and the agreement
      between collective (OKE) and single molecule (e.g., NMR) measurements of the
      orientational relaxation time suggests that orientational pair correlation is not
      significant in this liquid. The relative contributions of intermolecular
      interaction-induced and single-molecule orientational dynamics to the ultrafast
      part of the spectral density are discussed. Single-molecule librational
      orientational dynamics appear to dominate the ultrafast OKE response of liquid
      SO2. The temperature-dependent OKE data are transformed to the frequency domain
      to yield the Raman spectral density for the low-frequency intermolecular modes.
      These are bimodal with the lowest-frequency component arising from diffusive
      orientational relaxation and a higher-frequency component connected with the
      ultrafast time-domain response. This component is characterized by a shift to
      higher frequency at lower temperature. This result is analyzed in terms of a
      harmonic librational oscillator model, which describes the data accurately. The
      observed spectral shifts with temperature are ascribed to increasing
      intermolecular interactions with increasing liquid density. Overall, the dynamics
      of liquid SO2 are found to be well described in terms of molecular orientational
      relaxation which is controlled over every relevant time range by intermolecular
      interactions.

PMID- 16422611
TI  - Spatial hydration structures and dynamics of phenol in sub- and supercritical
      water.
AB  - The hydration structures and dynamics of phenol in aqueous solution at infinite
      dilution are investigated using molecular-dynamics simulation technique. The
      simulations are performed at several temperatures along the coexistence curve of
      water up to the critical point, and above the critical point with density fixed
      at 0.3 g/cm3. The hydration structures of phenol are characterized using the
      radial, cylindrical, and spatial distribution functions. In particular, full
      spatial maps of local atomic (solvent) density around a solute molecule are
      presented. It is demonstrated that in addition to normal H bonds with hydroxyl
      group of phenol, water forms pi-type complexes with the center of the benzene
      ring, in which H2O molecules act as H-bond donor. At ambient conditions phenol is
      solvated by 38 water molecules, which make up a large hydrophobic cavity, and
      forms on average 2.39 H bonds (1.55 of which are due to the hydroxyl group-water
      interactions and 0.84 are due to the pi complex) with its hydration shell. As
      temperature increases, the hydration structure of phenol undergoes significant
      changes. The disappearance of the pi-type H bonding is observed near the critical
      point. Self-diffusion coefficients of water and phenol are also calculated.
      Dramatic increase in the diffusivity of phenol in aqueous solution is observed
      near the critical point of simple point-charge-extended water and is related to
      the changes in water structure at these conditions.

PMID- 16422612
TI  - Two-dimensional Raman spectra of atomic solids and liquids.
AB  - We calculate third- and fifth-order Raman spectra of simple atoms interacting
      through a soft-core potential by means of molecular-dynamics (MD) simulations.
      The total polarizability of molecules is treated by the dipole-induced dipole
      model. Two- and three-body correlation functions of the polarizability at various
      temperatures are evaluated from equilibrium MD simulations based on a stability
      matrix formulation. To analyze the processes involved in the spectroscopic
      measurements, we divide the fifth-order response functions into symmetric and
      antisymmetric integrated response functions; the symmetric one is written as a
      simple three-body correlation function, while the antisymmetric one depends on a
      stability matrix. This analysis leads to a better understanding of the time
      scales and molecular motions that govern the two-dimensional (2D) signal. The 2D
      Raman spectra show novel differences between the solid and liquid phases, which
      are associated with the decay rates of coherent motions. On the other hand, these
      differences are not observed in the linear Raman spectra.

PMID- 16422613
TI  - Simultaneous estimation of phase behavior and second-derivative properties using
      the statistical associating fluid theory with variable range approach.
AB  - A modified statistical associating fluid theory (SAFT) with variable range
      version is presented using the family of m-n Mie potentials. The use of this
      intermolecular potential for modeling repulsion-dispersion interactions between
      the monomer segments, together with a new method for optimizing the molecular
      parameters of the equation of state, is found to give a very accurate description
      of both vapor-liquid equilibria and compressed liquid bulk properties (volumetric
      and derivative properties) for long-chain n-alkanes. This new equation improves
      other SAFT-like equations of state which fail to describe derivative properties
      such as the isothermal compressibility and the speed of sound in the condensed
      liquid phase. Emphasis is placed on pointing out that the key for modeling the
      latter properties is the use of a variable repulsive term in the intermolecular
      potential. In the case of the n-alkanes series, a clear dependence of the
      characteristic molecular parameters on increasing chain length is obtained,
      demonstrating their sound physical meaning and the consistency of the new fitting
      procedure proposed. This systematic method for optimizing the model parameters
      includes data on the saturation line as well as densities and speed of sound data
      in the condensed liquid phase, and the results show undoubtedly that the model
      performance is enhanced and its range of applicability is now widened, keeping in
      any case a good balance between the accuracy of the different estimated
      properties.

PMID- 16422614
TI  - Free-energy calculation of structure-H hydrates.
AB  - A molecular-dynamics (MD) simulation of structure-H hydrates was performed under
      constant pressure and temperature with 6120 TIP4P water molecules, 900 OPLS-UA
      methane molecules, and 180 large molecular guest substance (LMGS) molecules. The
      LMGS molecules were represented in the form of a one-site Lennard-Jones (LJ)
      model using the LJ parameters sigma and epsilon. In order to clarify the
      thermodynamic stability of structure-H hydrates, we calculated the free-energy
      difference, changing on the sigma and epsilon only of the LMGS molecules. In this
      simulation, stable crystals of structure-H hydrates and a minimum value of DeltaG
      were obtained at sigma approximately 6.2 A and large values of epsilon. All
      simulations were performed using the special-purpose computer hardware MDGRAPE-2.

PMID- 16422615
TI  - Cs*He(n) exciplexes in solid 4He.
AB  - We present a theoretical and experimental study of the laser-induced formation
      process and of the emission spectra of Cs*He(n) exciplexes in the hcp and bcc
      phases of solid helium. Two different exciplex molecules are detected: a linear
      triatomic Cs*He2, which can exist in two electronic states: APi(1/2) and
      BPi(3/2), and a larger complex, where six or seven He atoms form a ring around a
      single cesium atom in the 6P(1/2) state. A theoretical model is presented, which
      allows the interpretation of the experimentally observed spectra.

PMID- 16422616
TI  - Pair-correlation entropy of hydrophobic hydration: decomposition into
      translational and orientational contributions and analysis of solute-size
      effects.
AB  - We develop an efficient method to evaluate the translational and orientational
      contributions to the solute-water pair-correlation entropy that is a major
      component of the hydration entropy. A water molecule is modeled as a hard sphere
      of diameter dS=0.28 nm in which a point dipole and a point quadrupole of
      tetrahedral symmetry are embedded. A hard sphere of diameter dM, a hydrophobic
      solute, is immersed at infinite dilution in the model water. The pair-correlation
      entropy is decomposed into the translational and orientational contributions in
      an analytical manner using the angle-dependent Ornstein-Zernike integral equation
      theory. The two contributions are calculated for solutes with a variety of sizes
      (0.6<or=dM/dS<or=30). The effects of the solute-water attractive interaction are
      also studied. As dM becomes larger, the percentage of the orientational
      contribution first increases, takes a maximum value at dM=DM (DM/dS depends on
      the strength of the solute-water attractive interaction and is in the range of
      1.4-2), and then decreases toward a limiting value. The percentage of the
      orientational contribution reduces progressively as the solute-water attractive
      interaction becomes stronger. The physical origin of the maximum orientational
      restriction at dM=DM is discussed in detail.

PMID- 16422617
TI  - An atomistic simulation scheme for modeling crystal formation from solution.
AB  - We present an atomistic simulation scheme for investigating crystal growth from
      solution. Molecular-dynamics simulation studies of such processes typically
      suffer from considerable limitations concerning both system size and simulation
      times. In our method this time-length scale problem is circumvented by an
      iterative scheme which combines a Monte Carlo-type approach for the
      identification of ion adsorption sites and, after each growth step, structural
      optimization of the ion cluster and the solvent by means of molecular-dynamics
      simulation runs. An important approximation of our method is based on assuming
      full structural relaxation of the aggregates between each of the growth steps.
      This concept only holds for compounds of low solubility. To illustrate our method
      we studied CaF2 aggregate growth from aqueous solution, which may be taken as
      prototypes for compounds of very low solubility. The limitations of our
      simulation scheme are illustrated by the example of NaCl aggregation from aqueous
      solution, which corresponds to a solute/solvent combination of very high salt
      solubility.

PMID- 16422618
TI  - Theoretical interpretation of the line shape of crystalline adipic acid.
AB  - A general quantum theoretical approach of the upsilon(X-H) IR line shape of
      cyclic dimers of weakly H-bonded species in the crystal state is proposed. In
      this model, the adiabatic approximation (allowing to separate the high-frequency
      motion from the slow one of the H-bond bridge) is performed for each separate H
      bond bridge of the dimer and a strong nonadiabatic correction is introduced into
      the model via the resonant exchange between the fast-mode excited states of the
      two moieties. Quantum indirect damping and Fermi resonances are taken into
      account. The present model reduces satisfactorily to many models in the
      literature dealing with more special situations. It has been applied to the
      cyclic dimers of adipic acid in the crystal phase. It correctly fits the
      experimental line shape of the hydrogenated compound and predicts satisfactorily
      the evolution in the line shapes with temperature and the change in the line
      shape with isotopic substitution.

PMID- 16422619
TI  - The precursors of the solvated electron in methanol studied by femtosecond pump
      repump-probe spectroscopy.
AB  - Using UV photoionization and delayed near-infrared reexcitation pulses, a novel
      time-, frequency-, and polarization-resolved pump-repump-probe spectroscopy is
      conducted in the probing range of 450-2400 nm with improved experimental
      accuracy. Both the generation process and relaxation dynamics following selective
      repumping of intermediate species of the solvated electron are investigated and
      analyzed self-consistently with the help of a kinetic model. New insight in the
      intermediates of the trapped electron is gained leading to a unique microscopic
      picture.

PMID- 16422620
TI  - Monolayer alignment on azobenzene surfaces during UV light irradiation: analysis
      of optical polarized absorption measurement results and theoretical treatment.
AB  - The influence of the charge separation during the trans-cis conformational change
      on the surface of azobenzene 6Az10PVA monolayer on the polar liquid-crystal
      monolayer film, such as 4-n-pentyl-4'-cyanobiphenyl(5CB), is investigated. The
      effective anchoring energy (in the Rapini-Papolar form) is phenomenologically
      described in the framework of the molecular model, which takes into account the
      interaction between the surface polarization and surface electric field, for
      number of conformational states of the boundary surface. It is shown, using the
      experimental data for the voltage across the 6Az10PVA+5CB film, provided by the
      surface-potential technique, that the charge separation during the conformational
      changing, caused by the UV irradiation, may lead to changing of the surface
      alignment of liquid-crystalline molecules. The influence of the
      photoisomerization process on the orientational order parameter S2(t) using the
      optical polarized absorption measurement is also investigated.

PMID- 16422621
TI  - Two-dimensional surrogate Hamiltonian investigation of laser-induced desorption
      of NO/NiO(100).
AB  - The photodesorption of NO from NiO(100) is studied from first principles, with
      electronic relaxation treated by the use of the surrogate Hamiltonian approach.
      Two nuclear degrees of freedom of the adsorbate-substrate system are taken into
      account. To perform the quantum dynamical wave-packet calculations, a massively
      parallel implementation with a one-dimensional data decomposition had to be
      introduced. The calculated desorption probabilities and velocity distributions
      are in qualitative agreement with experimental data. The results are compared to
      those of stochastic wave-packet calculations where a sufficiently large number of
      quantum trajectories is propagated within a jumping wave-packet scenario.

PMID- 16422622
TI  - Ab initio multireference configuration-interaction study of hydrogen molecule
      activation by Cs-promoted Pt clusters.
AB  - The adsorption of the H2 molecule on CsnPt(5-n) bcc (111) clusters for Cs/Pt
      rates of 20%, 40%, and 80% is studied using ab initio multiconfigurational self
      consistent field plus multireference configuration-interaction variational and
      perturbative calculations. The H2 interaction with the clusters is studied in
      ground and excited states with geometry optimization, where the hydrogen
      adsorption takes place by a Pt atom. These calculations are compared with those
      of H2 adsorption on Pt4. The most stable configurations of Cs/Pt4 and Cs2Pt3
      clusters (Cs/Pt rates of 20% and 40%) are a doublet and a closed-shell singlet,
      respectively. Both clusters capture and activate the hydrogen molecule and their
      behaviors resemble Pt4. The H2 capture distances are, respectively, similar and
      smaller than Pt4 capture distances, while the H-H bond dissociation distances are
      similar and bigger than those of Pt4; however, none of them presents activation
      barriers. The most stable Cs4Pt cluster (Cs/Pt rate of 80%) is also a closed
      shell singlet; it also captures and activates the hydrogen molecule and shows a
      different behavior as compared with Cs/Pt4, Cs2Pt3, and Pt4 clusters. The capture
      distance is quite smaller and is obtained after surmounting an activation
      barrier. For all clusters studied here, no hydrogen absorption was observed, only
      the adsorption of H2.

PMID- 16422623
TI  - Theoretical study of one-, two-, and three-photon absorption properties for a
      series of Y-shaped molecules.
AB  - In this paper, the equilibrium geometries, one-, two-, and three-photon
      absorption properties, and the transition nature of a series of Y-shaped
      molecules which possess an imidazole-thiazole core have been theoretically
      studied by using the parametrization model 3 and Zerner's intermediate neglect of
      differential overlap methods. Our calculated results have confirmed the
      experimental findings that the investigated molecules are all promising
      multiphoton absorption materials and both the two-photon absorption and the three
      photon absorption cross sections are seriatim increscent along with the increase
      of the electron-donor strength. The nonlinear optical phenomenon originates from
      the intramolecular charge transfer within the pi-conjugated system. The
      calculated results indicate that the heterocyclic core increases the two- and
      three-photon absorption cross sections due to its pi-excessive nature. So it can
      provide more free electrons to enlarge the charge transfer within the molecule
      system. In addition, the design of Y shape and the sulfonyl-based electron
      accepting group play a part in the enhancement of multiphoton absorption. It is
      notable that molecules with heterocyclic core will provide favorable condition
      for multiphoton absorption applications.

PMID- 16422624
TI  - Induction of strand breaks by low-energy electrons (8-68 eV) in a self-assembled
      monolayer of oligonucleotides: effective cross sections and attenuation lengths.
AB  - Self-assembled monolayers of 5'-32P-labeled 3'-thiolated oligonucleotides
      chemisorbed on gold were bombarded by low-energy electrons (LEE) of 8-68 eV.
      Shorter 5'-32P-oligonucleotides produced by LEE-induced strand breaks were
      separated with denaturing polyacrylamide gel electrophoresis and quantified by
      phosphor imaging. The yields of short oligonucleotides (y) decrease exponentially
      with their length (n), following the equation y=ae-bn, where a and b are
      constants, which are related to the average effective cross section per
      nucleotide for DNA strand break (sigmaeff) and the attenuation length (AL=1b) of
      LEE, respectively. The AL decreases with LEE energies from 2.5+/-0.6 nm at 8 eV
      to 0.8+/-0.1 nm at 68 eV, whereas sigmaeff increases from (3+/-1)x10(-18) to
      (5.1+/-1.6)x10(-17) cm2 within the same energy range. The energy dependence of
      sigmaeff shows a resonance peak of (2.8+/-0.9)x10(-17) cm2 at 18 eV superimposed
      on a monotonically rising curve. Transient electron attachment to a sigma* anion
      state of the deoxyribose group, followed by dipolar dissociation into H- and the
      corresponding positive-ion radical, leading to C-O bond cleavage, is proposed to
      account for this maximum.

PMID- 16422625
TI  - Asymmetric bridging of interconnected pores by encased semiflexible
      macromolecules.
AB  - An increase of chain rigidity of macromolecule encased in interconnected cavities
      leads to bridging conformational transition in which polymer molecule at certain
      conditions spans the cavities. This is a similar phenomenon to that described for
      flexible chains on increase of confinement. Chain stiffness introduces, however,
      a delicate effect of interplay between confinement, chain stiffness, and
      concentration that leads to a breakup of symmetric bridging conformation to a
      striking asymmetric conformation even in the symmetric system of cavities. We
      provide the first data on this transition with complex translocation landscape
      and offer a tentative explanation.

PMID- 16422626
TI  - Wetting behavior of low-index cubic SiC surfaces.
AB  - We report on the interaction of water molecules with polar and nonpolar
      stoichiometric surfaces of cubic silicon carbide, as described by ab initio
      molecular dynamics at finite temperature. Our calculations show that,
      irrespective of coverage, in the gas phase water spontaneously dissociates on
      both polar Si-terminated (001) and nonpolar (110) surfaces, following similar
      mechanisms. The specific geometric arrangement of atoms on the outermost surface
      layer is responsible for water orientation and coordination and thus plays a
      major role in determining surface reactivity. This is found to be the case also
      for water on a computer-generated amorphous-SiC surface. In addition, from a
      macroscopic standpoint, the ability of the two crystalline surfaces with
      different polarities to induce water dissociation can be related to the
      similarities of their ionization potentials.

PMID- 16422627
TI  - The rutile TiO2 (110) surface: obtaining converged structural properties from
      first-principles calculations.
AB  - We investigate the effects of constraining the motion of atoms in finite slabs
      used to simulate the rutile TiO2 (110) surface in first-principles calculations.
      We show that an appropriate choice of fixing atoms in a slab eliminates spurious
      effects due to the finite size of the slabs, leading to a considerable
      improvement in the simulation of the (110) surface. The method thus allows for a
      systematic improvement in convergence in calculating both geometrical and
      electronic properties. The advantages of this approach are illustrated by
      presenting the first theoretical results on the displacement of the surface atoms
      in agreement with experiment.

PMID- 16422628
TI  - Screened exchange hybrid density-functional study of the work function of
      pristine and doped single-walled carbon nanotubes.
AB  - We present a detailed study of the work function of pristine and doped single
      walled carbon nanotubes (SWCNTs) using a novel screened exchange hybrid density
      functional. We find that SWCNTs with diameters larger than 0.9 nm tend
      asymptotically and smoothly to the graphene limit of 4.6 eV. On the other hand,
      the work function of narrow tubes exhibits a strong dependence on their diameter
      and chiral angle. Boron or nitrogen doping, with concentrations from 1% to 2%,
      not only changes the electronic behavior by introducing new states around the
      Fermi level, but also produces a significant change of the work function that can
      vary between 3.9 (N doping) and 5.2 eV (B doping).

PMID- 16422629
TI  - Formation of regular nanoscale undulations on a thin polymer film imprinted by a
      soft mold.
AB  - We observed the formation of regular nanoscale undulations on a polystyrene film
      when imprinted by a soft poly(dimethylsiloxane) mold above the polymer's glass
      transition temperature. The shape of the wave was reminiscent of a buckling wave
      frequently observed for a metal film supported on an elastomeric substrate. We
      derived a simple theoretical model based on an anisotropic buckling of the
      polymer film rigidly bound to a substrate, which agrees well with the experiment.

PMID- 16422630
TI  - Surface reconstructions and stability of X-shaped carbon nanotube junction.
AB  - A complete surface reconstruction takes place after a local connection between
      two crossed tubes is established, leading to the creation of an extended X-shaped
      junction constituted by topological defects with smooth negative curvature.
      Molecular-dynamics simulations show that the surface reconstructions occur
      through (1) generalized Stone-Wales transformation and (2) the movement of sp and
      sp3 atoms and their transformation to sp2 atoms by bond rearrangement. Based on
      both the principle of energy minimization and a generalized Euler's rule, it is
      demonstrated that the most stable structure for X junctions contains only 12
      heptagons. The annealing temperature influences the topological structure and
      stability of junctions.

PMID- 16422631
TI  - The elastic constants and related properties of the energetic material
      cyclotrimethylene trinitramine (RDX) determined by Brillouin scattering.
AB  - The acoustic phonons of cyclotrimethylene trinitramine (RDX) have been studied
      using Brillouin scattering. The analysis of the acoustic-phonon velocities
      allowed determination of the complete stiffness tensor for this energetic
      material. The results are compared to other recent experimental and theoretical
      determinations of the RDX elastic constants, bulk moduli, and shear moduli. The
      observed ordering of elastic constants, C11>C22>C33, is qualitatively associated
      with a (001) cleavage plane and molecular packing. This interpretation is further
      corroborated by the linear compressibilities plotted in three crystallographic
      planes, and a comparison to recent theoretical and experimental hydrostatic
      compression studies on RDX. Finally, the elasticity of RDX is compared to a
      recently published report on the beta polymorph of cyclotetramethylene
      tetranitramine's elasticity, and is related to several proposed mechanisms for
      detonation initiation.

PMID- 16422632
TI  - Cluster kinetics and dynamics during spinodal decomposition.
AB  - Spinodal decomposition (barrierless phase transition) is a spontaneous phase
      separation caused by conditions that force the system to become thermodynamically
      unstable. We consider spinodal decomposition to occur under conditions of large
      supersaturation S and/or small ratio of interfacial to thermal energies omega,
      such that the computed number of monomers in a critical nucleus xi*=(omega/ln S)3
      is less than unity. The small critical nucleus size is consistent with a
      negligible energy barrier for initiating condensation. Thus, in contrast to
      conventional opinion, it is suggested that the spinodal decomposition is related
      to the homogeneous nucleation of metastable fluids. Population balance equations
      show how clusters aggregate and rapidly lead to phase separation. Different mass
      dependences of aggregation rate coefficients are proposed to investigate the
      fundamental features of spinodal decomposition. When the mass dependency is an
      integer, the equations are solved by the moment technique to obtain analytical
      solutions. When the mass dependency is a noninteger, the general cases are solved
      numerically. All solutions predict the two time regimes observed experimentally:
      the average length scale of condensed-phase domains increases as a power law with
      an exponent of 1/3 at early times, followed by a linear increase at longer times.

PMID- 16422633
TI  - Phase of molecular ink in nanoscale direct deposition processes.
AB  - We report the first observation of a phase transition in a nanoscale direct
      deposition process. This transition involves the melting of molecular ink layers
      in dip-pen nanolithography, and it is observed by measuring the temperature
      dependence of the growth rate of the deposited pattern. The results are
      interpreted using a diffusion equation approach in conjunction with a "double
      molecular-layer" model of the adsorbed molecules on the atomic force microscope
      tip. The theory provides a qualitative explanation for the dependence of the
      pattern growth rate on solvent and adsorbed water as well as on temperature.

PMID- 16422634
TI  - Desorption dynamics of deuterium molecules from the Si(100)-(3x1) dideuteride
      surface.
AB  - We measured polar angle (theta)-resolved time-of-flight spectra of D2 molecules
      desorbing from the Si(100)-(3x1) dideuteride surface. The desorbing D2 molecules
      exhibit a considerable translational heating with mean desorption kinetic
      energies of approximately 0.25 eV, which is mostly independent of the desorption
      angles for 0 degrees<or=theta<or=30 degrees. The observed desorption dynamics of
      deuterium was discussed along the principle of detailed balance to predict their
      adsorption dynamics onto the monohydride Si surface.

PMID- 16422635
TI  - Structure and binding energies of unsaturated hydrocarbons on Si(001) and
      Ge(001).
AB  - The adsorption of acetylene, ethylene, and benzene on the Si(001) and Ge(001)
      surfaces is investigated by first-principles density-functional calculations
      within the generalized-gradient approximation. We find that the adsorption
      energies of the three hydrocarbons containing a triple bond, a double bond, and a
      pi-conjugated aromatic ring decrease as the sequence of C2H2>C2H4>C6H6. We also
      find that the bondings of acetylene, ethylene, and benzene to Ge(001) are much
      weaker than those to Si(001). As a result, benzene is weakly bound to Ge(001)
      while it is chemisorbed on Si(001), consistent with temperature-programmed
      desorption data.

PMID- 16422636
TI  - Shape versus inverse-shape selective adsorption of alkane isomers in carbon
      nanotubes.
AB  - Simulation results are reported for the adsorption of pure pentane (C5) isomers
      and their ternary mixture in a series of open-ended armchair-type (m,m) single
      walled carbon nanotubes (SWNTs). Inverse-shape selective adsorption occurs in the
      order of nC5<iC5<neoC5 only in the (7,7) SWNT as a result of the length entropy
      effect. In the larger (20,20) and (10,10) SWNTs, shape selective adsorption
      occurs in the order of nC5>or=iC5>neoC5 as a result of the configurational
      entropy effect. In smaller SWNTs, depending on the diameter, only nC5 adsorbs, or
      no adsorption at all occurs. The entropy effects are found to lead to a large
      adsorptive separation among the C5 isomers from their mixture. Using the ideal
      adsorbed-solution theory with data on the adsorption of only the pure isomers, we
      predict mixture adsorption. The agreement between predictions and simulations
      deteriorates with decreasing diameter of the SWNT.

PMID- 16422637
TI  - Organometallic molecular rectification.
AB  - We study the rectification of current through a single molecule with an intrinsic
      spatial asymmetry. The molecule contains a cobaltocene moiety in order to take
      advantage of its relatively localized and high-energy d states. A rectifier with
      large voltage range, high current, and low threshold can be realized. The
      evolution of molecular orbitals under both forward and reverse biases is captured
      in a self-consistent nonequilibrium Green function plus density functional theory
      description. Our calculations demonstrate the plausibility of making excellent
      molecular diodes by using metallocenes, pointing to a fruitful class of
      molecules.

PMID- 16422638
TI  - Investigation of a binuclear gallium complex with bipolar charge transporting
      capability for organic light-emitting diodes.
AB  - Detailed theoretical and experimental investigations have been presented on a
      novel binuclear gallium complex Ga2(saph)2q2, a potentially active and novel
      material for organic light-emitting diodes (OLEDs). The density-functional theory
      has been employed to shed light on the reason why this complex exhibits bipolar
      character. Theoretical results, such as ionization potential and electron
      affinity, and optimized geometries are in good agreement with what we have
      obtained experimentally. Our theoretical analysis provides new insight into the
      origin of bipolar features. Such character enables the gallium complex to become
      a prosperous hole and electron transporter used to fabricate single-layer OLEDs,
      which exhibit better electroluminescence compared with those originated from the
      previously well-adopted tri(8-hydroxyquinoline)aluminum (Alq3). An OLED device of
      single Ga2(saph)2q2 layer exhibiting desirable performances has been fabricated,
      which is in good agreement with the theoretical analysis.

PMID- 16422639
TI  - Excitations of lithium ammonia complexes studied by inelastic x-ray scattering.
AB  - We have carried out high-resolution inelastic x-ray scattering measurements of
      the excitations of lithium dissolved in ammonia. The incident x-ray energy was
      21.6 keV and the resolution was about 2 meV. Several different excitations are
      observed in the energy range of 0-60 meV (0-500 cm(-1)). In addition to acoustic
      phonons at low energies, we see excitations that are associated with vibrations
      of Li(NH3)4+ complexes. We examined these excitations as a function of momentum
      transfer, lithium concentration, temperature, and state of the system (solid
      versus liquid). Data are compared with Hartree-Fock and density-functional theory
      calculations of the excitations of this complex, which agree well with the
      measured excitation energies.

PMID- 16422640
TI  - Determination of surface tension in binary mixtures using transition-matrix Monte
      Carlo.
AB  - We present a methodology based on grand-canonical transition-matrix Monte Carlo
      and finite-size scaling analysis to calculate surface tensions in binary
      mixtures. In particular, mixture transition-matrix Monte Carlo is first used to
      calculate apparent, system-size-dependent free-energy barriers separating
      coexisting fluid phases. Finite-size scaling is then used to extrapolate these
      values to the infinitely large system limit to determine the true thermodynamic
      surface tension. A key distinction of the methodology is that it yields the
      entire isothermal surface-tension curve for a binary mixture in a relatively
      small number of simulations. We demonstrate the utility of the method by
      calculating surface-tension curves for three binary Lennard-Jones mixtures. While
      we have only examined the surface tension of simple fluids in this work, the
      method is general and can be extended to molecular fluids as well as to determine
      interfacial tensions of liquid-liquid interfaces.

PMID- 16422641
TI  - From cluster to bulk: size dependent energetics of silica and silica-water
      interaction.
AB  - We present our computational investigations on the energetics of clusters that
      consist of H2O and SiO2 using first-principles Born-Oppenheimer molecular
      dynamics method. Cohesive energy and hydration energy of both pure (or dry) and
      hydroxylated (or wet) ring-structured clusters have been investigated as
      functions of system size. We have found clear trends of energy as the cluster
      size increases. Energetics of a small silica nano-rod that contains 108 atoms is
      also obtained as a middle reference point for size evolution. Results from
      cluster and nano-rod calculations are compared with values from bulk quartz
      calculations using the same level of theoretical treatments.

PMID- 16422642
TI  - Entropy production during reversible polymerization in nonideal systems.
AB  - A general route is shown to calculate the entropy production sigma as function of
      time t in a closed system during reversible polymerization. We treat the polymer
      molecules to behave nonideal and apply exemplarily the classical Flory-Huggins
      theory to get explicit expressions for the activity coefficient. At the beginning
      of the polymerization the system is in a nonequilibrium state where chemical
      reactions take place that irreversibly drive the system towards equilibrium with
      sigma approaching zero in the limit t-->infinity. The time-dependent course of
      the entropy production is explicitly calculated for two cases where the reaction
      starts (i) from monomer molecules polymerizing to a defined number average chain
      length xn,eq and (ii) from monodisperse polymer molecules reacting with each
      other under the constrain that xn is the same at the beginning and the end of the
      reaction. In both cases we find that the nature of the activity coefficient has
      an important effect on the curvature of sigma which may considerably differ from
      that of an ideal behavior.

PMID- 16422643
TI  - Elongation/compaction of giant DNA caused by depletion interaction with a
      flexible polymer.
AB  - Structural changes in giant DNA induced by the addition of the flexible polymer
      Polyethylene Glycol (PEG) were examined by the method of single-DNA observation.
      In dilute DNA conditions, individual DNA assumes a compact state via a discrete
      coil-globule transition, whereas in concentrated solution, DNA molecules exhibit
      an extended conformation via macroscopic phase segregation. The long-axis length
      of the stretched state in DNA is about 10(3) times larger than that of the
      compact state. Phase segregation at high DNA concentrations occurs at lower PEG
      concentrations than the compaction at low DNA concentrations. These opposite
      changes in the conformation of DNA molecule are interpreted in terms of the free
      energy, including depletion interaction.

PMID- 16422644
TI  - Deforming biological membranes: how the cytoskeleton affects a polymerizing
      fiber.
AB  - We give a theoretical treatment of the force exerted by a fluctuating membrane on
      a polymer rod tip, taking into account the effects of an underlying biological
      cytoskeleton by way of a simple harmonic dependence on displacement. We also
      consider theoretically and experimentally the dynamics of a growing fiber tip
      under the influence of such a fluctuation-induced membrane force, including the
      effects of an underlying cytoskeletal network. We compare our model with new
      experimental data for the growth of hemoglobin fibers within red blood cells,
      revealing a good agreement. We are also able to estimate the force and
      membrane/cytoskeletal displacement required to stall growth of, or buckle, a
      growing fiber. We discuss the significance of our results in a biological
      context, including how the properties of the membrane and cytoskeleton relate to
      the thermodynamics of rod polymerization.

PMID- 16422645
TI  - Monte Carlo phase diagram for diblock copolymer melts.
AB  - A partial phase diagram is constructed for diblock copolymer melts using lattice
      based Monte Carlo simulations. This is done by locating the order-disorder
      transition (ODT) with the aid of a recently proposed order parameter and
      identifying the ordered phase over a wide range of copolymer compositions
      (0.2<or=f<or=0.8). Consistent with experiments, the disordered phase is found to
      exhibit direct first-order transitions to each of the ordered morphologies. This
      includes the spontaneous formation of a perforated-lamellar phase, which
      presumably forms in place of the gyroid morphology due to finite-size and/or
      nonequilibrium effects. Also included in our study is a detailed examination of
      disordered cylinder-forming (f=0.3) diblock copolymers, revealing a substantial
      degree of pretransitional chain stretching and short-range order that set in well
      before the ODT, as observed previously in analogous studies on lamellar-forming
      (f=0.5) molecules.

PMID- 16422646
TI  - Local-structural diversity and protein folding: application to all-beta off
      lattice protein models.
AB  - Global measures of structural diversity within a distribution of biopolymers,
      such as the radius of gyration and percent native contacts, have proven useful in
      the analysis of simulation data for protein folding. In this paper we describe a
      statistical-based methodology to quantify the local structural variability of a
      distribution of biopolymers, applied to 46- and 69-"residue" off-lattice, three
      color model proteins. Each folds into beta-barrel structures. First we perform a
      principal component analysis of all interbead distance variables for a large
      number of independent, converged Boltzmann-distributed samples of conformations
      collected at each of a wide range of temperatures. Next, the principal component
      vectors are subjected to orthogonal (varimax) rotation. The results are displayed
      on so-called "squared-loading" plots. These provide a quantitative measure of the
      contribution to the sample variance of the position of each residue relative to
      the others. Dominant structural elements, those having the largest structural
      diversity within the sampled distribution, are responsible for peaks and
      shoulders observed in the specific heat versus temperature curves, generated
      using the weighted histogram analysis method. The loading plots indicate that the
      local-structural diversity of these systems changes gradually with temperature
      through the folding transition but radically changes near the collapse transition
      temperature. The analysis of the structural overlap order statistic suggests that
      the 46-mer thermodynamic folding transition involves the native state and at
      least three other nearly native intermediates. In the case of the 46-mer protein
      model, data are generated at sufficiently low temperatures that squared-loading
      plots, coupled with cluster analysis, provide a local and energetic description
      of its glassy state.

PMID- 16422647
TI  - A thermodynamic approach to the fragility of glass-forming polymers.
AB  - We have connected the dynamic fragility, namely, the steepness of the relaxation
      time variation upon temperature reduction, to the excess entropy and heat
      capacity of a large number of glass-forming polymers. The connection was obtained
      in a natural way from the Adam-Gibbs equation, relating the structural relaxation
      time to the configurational entropy. We find a clear correlation for a group of
      polymers. For another group of polymers, for which this correlation does not
      work, we emphasize the role of relaxation processes unrelated to the alpha
      process in affecting macroscopic thermodynamic properties. Once the residual
      excess entropy at the Vogel temperature is removed from the total excess entropy,
      the correlation between dynamic fragility and thermodynamic properties is
      reestablished.

PMID- 16422648
TI  - Lifetime determination of fluorescence and phosphorescence of a series of
      oligofluorenes.
AB  - The photoluminescence (PL) properties of oligofluorenes with 2-ethylhexyl group
      in 9, 9' position in solution and as thin films were investigated by time
      resolved techniques at both room temperature and 77 K. The fluorescence lifetimes
      of the oligomers decrease with chain length. The lifetimes tau follow the
      relation tau=386+808(1/n) (ps) where n is the number of fluorene units in the
      oligomer. Concentration and laser excitation energy dependences of PL spectra of
      the oligofluorenes are also given. Phosphorescence was observed for
      oligofluorenes in the frozen matrix of MTHF at 77 K. The lifetime of
      phosphorescence increases with increasing molecular length. Similar emission
      bands were observed for oligofluorenes with a central ketogroup. A lifetime
      analysis clearly reveals that the "green emission" of the oligomers free of
      ketogroups results from a phosphorescence with lifetime tau of 3 ms while the
      green emission from the keto-oligomer is a fluorescence from a charge transfer pi
      pi* level of tau=8 ns.

PMID- 16422649
TI  - Incompatible strains associated with defects in nematic elastomers.
AB  - In a nematic elastomer the deformation of the polymer network chains is coupled
      to the orientational order of the mesogenic groups. Statistical arguments have
      derived the so-called neoclassical free energy that models this coupling. Here we
      show that the neoclassical model supplemented by the usual Frank energy predicts
      incompatible network strains associated with the formation of standard nematic
      textures. The incompatibility is measured by the Riemann curvature tensor, which
      we find to be nonzero for both radial hedgehog defects and escaped disclinations
      of strength +1 in circular cylinders. Analogous problems for conventional
      nonlinearly elastic solids do not possess solutions with such incompatibilities.
      Compatibility in nematic elastomers would require either more complicated nematic
      textures in elastomers than in conventional (polymeric and low molecular weight)
      liquid crystals or a free-energy density more complicated than the neoclassical
      expression.

PMID- 16422650
TI  - Polymer chains in a soft nanotube: a Monte Carlo study.
AB  - We study the equilibrium properties of flexible polymer chains confined in a soft
      tube by means of extensive Monte Carlo simulations. The tube wall is that of a
      single sheet six-coordinated self-avoiding tethered membrane. Our study assumes
      that there is no adsorption of the chain on the wall. By varying the length N of
      the polymer and the tube diameter D we examine the variation of the polymer
      gyration radius Rg and diffusion coefficient Ddiff in soft and rigid tubes of
      identical diameter and compare them to scaling theory predictions. We find that
      the swollen region of the soft tube surrounding the chain exhibits a cigarlike
      cylindrical shape for sufficiently narrow tubes with D<<Rg. The observed scaling
      of static conformational properties with chain length N and tube diameter D
      follows the predictions of scaling theory and displays no significant difference
      between soft and rigid tubes. The Brownian dynamics of the polymer diffusion in a
      rigid tube is found to slow down in a tube with soft walls by an amount which
      depends on the Rg/D ratio albeit the relaxation time tau(parallel) for diffusive
      motion along the tube still scales as tau(parallel) proportional, N3.

PMID- 16422651
TI  - Evaluating the conformational entropy of macromolecules using an energy
      decomposition approach.
AB  - We have developed a novel method to compute the conformational entropy of any
      molecular system via conventional simulation techniques. This method only
      requires that the total energy of the system is available and that the
      Hamiltonian is separable, with individual energy terms for the various degrees of
      freedom. Consequently the method, which we call the energy decomposition (Edcp)
      approach, is general and applicable to any large polymer in implicit solvent.
      Edcp is applied to estimate the entropy differences due to the peptide and ester
      groups in polyalanine and polyalanil ester. Ensembles over a wide range of
      temperatures were generated by replica exchange molecular dynamics, and densities
      of states were estimated using the weighted histogram analysis method. The
      results are compared with those obtained via evaluating the P ln P integral or
      employing the quasiharmonic approximation, other approaches widely employed to
      evaluate the entropy of molecular systems. Unlike the former method, Edcp can
      accommodate the correlations present between separate degrees of freedom. In
      addition, the Edcp model assumes no specific form for the underlying fluctuations
      present in the system, in contrast to the quasiharmonic approximation. For the
      molecules studied, the quasiharmonic approximation is observed to produce a good
      estimate of the vibrational entropy, but not of the conformational entropy. In
      contrast, our energy decomposition approach generates reasonable estimates for
      both of these entropy terms. We suggest that this approach embodies a simple yet
      effective solution to the problem of evaluating the conformational entropy of
      large macromolecules in implicit solvent.

PMID- 16422652
TI  - Patch-distribution effect on diffusion-limited process in dilute suspension of
      partially active spheres.
AB  - The normalized overall rate constant, kp/kf for diffusion-limited processes in a
      dilute suspension of spheres, partially covered with active patches of varying
      distribution states, is studied with sped-up Brownian dynamic simulations. A
      dimensionless separation index Is is defined to quantify the characteristics of
      patch distribution on the sphere surfaces, with values of 0 and 1 corresponding
      to the states of the most compact and loosest patch distributions, respectively.
      Remarkably, the normalized overall rate constant is found to strongly correlate
      with the dimensionless separation index at fixed patch coverage fcover exhibiting
      a positive, linear relationship. In addition, the slope of the kp/kf vs Is line,
      a measure of sensitivity of kp/kf to variation in the separation state of the
      distributed patches, is found to depend on patch coverage and patch size. This
      sensitivity exhibits a maximum value with respect to an increase in patch
      coverage, and the magnitude of the maximum sensitivity decreases with increasing
      patch size. The patch coverage, at which the maximum sensitivity occurs,
      increases with increasing patch size.

PMID- 16422653
TI  - Interfacial and volumetric kinetics of the beta-->delta phase transition in the
      energetic nitramine octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine based on the
      virtual melting mechanism.

PMID- 16422654
TI  - The effect of surface relaxation on the N2 dissociation rate on stepped Ru: a
      transition state theory study.

PMID- 16422659
TI  - The effect of age and education transformations on neuropsychological test scores
      of persons with diffuse or bilateral brain damage.
AB  - Heaton, Grant, and Matthews (1991) published procedures for adjusting raw scores
      on various neuropsychological tests according to the individual's age and
      education. Despite rather widespread use of these score conversions in both
      clinical work and research publications, there have been very few investigations
      to evaluate the accuracy or limitations of these score transformations. This
      study was based on 52 persons with brain damage who had a range of verified brain
      injuries or disease. Raw scores were transformed according to the Heaton, Grant,
      and Matthews (HGM) procedure and also according to Reitan and Wolfson's
      Neuropsychological Deficit Scale (RW NDS) score procedure. The latter method is a
      straightforward transformation of raw scores and does not adjust for age or
      education. The number of normal (vs. impaired) scores was 1.74 times greater
      using the Heaton, Grant, and Matthews method than when using the Reitan and
      Wolfson method, yielding a chi2 value of 32.66 (p < .001). These results suggest
      that impairment in this brain-damaged group was identified less often when using
      the Heaton, Grant, and Matthews procedure than when using a method that
      represented the raw scores directly. The clinical and forensic implications of
      these findings are discussed. More research on this issue is needed.

PMID- 16422660
TI  - A model of the development of frontal lobe functioning: findings from a meta
      analysis.
AB  - Although past research has provided an initial examination of maturational trends
      of frontal lobe functioning, it has not yielded a unifying developmental model.
      The purpose of this study was to generate a model representing the maturation of
      frontal lobe function as determined principally through neuropsychological tests.
      A meta-analytic review of the literature on the development of frontal lobe
      functioning was conducted. Journal articles were identified through an initial
      search of PsycInfo, Medline, and ERIC for the years 1984-2004 using key words
      executive function*, frontal function*, development*, and age. Analyses of effect
      size differences across age groups assisted in determining the developmental
      patterns for commonly used measures of frontal functioning by providing a common
      metric of growth. Age-related increases across the different frontal functions
      were averaged providing overall age-related increases in performance. A plot was
      made of the development of frontal lobe functioning using the mean effect size of
      change in performance across age groups. The model of the development of frontal
      lobe functioning suggests a staging of development that begins in early childhood
      with the maturation of frontal functioning and continues, although at a decreased
      rate, into adolescence and early adulthood.

PMID- 16422662
TI  - Ipsative comparisons of WISC-IV index scores.
AB  - The Wechsler Intelligence Scale for Children-4th Edition (Wechsler, 2003a) yields
      standard scores for four indexes that can be compared when practitioners examine
      within-child variability. The test manual provides pairwise comparison tables
      that clinicians can use to examine the scale variability, but it does not
      adequately caution them about the statistical pitfalls of multiple pairwise
      comparisons (e.g., inflated error rate). An alternative to the pairwise
      comparison approach called an ipsative method can be used to compare the 4 WISC
      IV standard scores to an individual child's mean of the 4 index scores with more
      control over the error rate. These values were computed at the .05 and .01 levels
      following the method used by Naglieri (1993) for the Wechsler Intelligence Scale
      for Children-3rd Edition (WISC-III; Wechsler, 1991) as originally suggested by
      Davis (1959) and modified by Silverstein (1982) for previous versions of
      Wechsler's scales and other multiscore intelligence tests. An example of the use
      of the technique is provided, as are interpretive cautions.

PMID- 16422661
TI  - An examination of the California Verbal Learning Test II to detect incomplete
      effort in a traumatic brain-injury sample.
AB  - Clinical neuropsychologists are frequently called on to distinguish people who
      appear impaired on neuropsychological testing due to putting forth incomplete
      effort from those who have genuine cognitive deficits. Because traditional
      measures of effort are becoming accessible over the Internet and within the legal
      community and their purpose may be obvious to potential malingerers,
      nontraditional effort measures have been newly investigated. Using discriminant
      function analysis, this study explores whether five California Verbal Learning
      Test-Second Edition (CVLT-II) variables could differentiate between head-injured
      patients who were putting forth full effort and those who were putting forth
      incomplete effort. The discriminant function seemed to best predict those who put
      forth adequate effort while testing (95.6% correct) but not those who failed to
      put forth adequate effort during testing (only 13.8% correct). Hence, although
      the overall classification rate was moderately impressive (75.8%), the model's
      sensitivity in classification of the incomplete effort group was low. Cautious
      applications for these findings are discussed.

PMID- 16422663
TI  - Cognitive findings after transient global amnesia: role of prefrontal cortex.
AB  - The aim of this study is to verify, after recovery, the presence of specific
      patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen
      patients with the diagnosis of TGA were submitted to a battery of
      neuropsychological tests and compared to a matched control group. We found
      significant qualitative and quantitative differences between TGA patients and
      controls in the California Verbal Learning Test (CLVT) and Rey-Osterrieth Complex
      Figure Test. Our data support the presence of selective cognitive dysfunctions
      after the clinical recovery. Moreover, for Verbal Fluency, Digit Span Backward,
      and Number of Clusters in the CVLT short-term memory test, the relation resulted
      as positively related with the temporal interval from the TGA episode. Reduction
      of categorical learning, attention, and qualitative alterations of spatial
      strategy seem to postulate a planning defect due to a prefrontal impairment.

PMID- 16422665
TI  - Familiarity effect on retrieval: a neuropsychological case study.
AB  - NM, who suffered traumatic brain injury (TBI) to the prefrontal cortex (PFC), was
      compared with a diffuse axonal injury (DAI) patient on tasks of free recall, cued
      recall and recognition memory. We manipulated the familiarity of items to explore
      the effects of item strength on retrieval. On free recall, NM performed best
      during the high-familiarity picture condition. On cued recall, he performed best
      during the high-familiarity word condition. Although high familiarity improved
      his accuracy on picture items in free recall, low familiarity improved his
      recognition of words. The patient with DAI did not show these patterns. The role
      of the PFC in memory is discussed in terms of plausible recognition processes.

PMID- 16422667
TI  - Osmol gap as a surrogate marker for serum propylene glycol concentrations in
      patients receiving lorazepam for sedation.
AB  - STUDY OBJECTIVES: To correlate serum propylene glycol concentration with osmol
      gap, serum lactate concentration, and amount of propylene glycol administered to
      mechanically ventilated patients receiving continuous infusions of lorazepam (80%
      propylene glycol by weight), and to characterize the prevalence of
      hyperosmolality and range of serum propylene glycol concentrations in this
      patient population. DESIGN: Prospective, controlled, observational study.
      SETTING: Adult surgical and cardiothoracic intensive care units (ICUs) of a 1200
      bed, urban, tertiary care, teaching hospital. PATIENTS: Sixty-four consecutively
      enrolled intensive care patients requiring mechanical ventilation and
      pharmacologic sedation. INTERVENTION: Thirteen patients received continuous
      infusions of high-dose lorazepam (> or = 6 mg/hr) for a minimum of 36 hours, and
      26 received continuous infusions of low-dose lorazepam (2-5.99 mg/hr) for 36
      hours. Twenty-five control patients received sedatives that did not contain
      propylene glycol. MEASUREMENTS AND MAIN RESULTS: Serum propylene glycol and
      lactate concentrations, osmolality, and basic metabolic profiles were obtained 72
      108 hours after ICU admission. Clinical data, drug administration, and severity
      of illness scores were recorded. Osmol gap and the amount of propylene glycol
      administered before serum sampling predicted propylene glycol concentrations
      (r(2)=0.692, p<0.05). Osmol gap alone also predicted serum propylene glycol
      concentrations (r(2)=0.532, p<0.05). Serum lactate concentrations did not
      correlate with serum propylene glycol concentrations. Unlike the low-dose and
      control patients, eight (62%) of 13 high-dose patients had osmol gaps above 10.
      All 13 high-dose patients had serum propylene glycol concentrations previously
      associated with toxicity. CONCLUSION: Osmol gap can be used as a surrogate marker
      for serum propylene glycol concentration. In critically ill patients receiving
      lorazepam for sedation, an osmol gap above 10 was associated with concentrations
      previously reported to cause toxicity.

PMID- 16422674
TI  - Learning for reality. 1975.

PMID- 16422677
TI  - The concept of nursing. 1977.

PMID- 16422668
TI  - Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties
      of a natural proteolytic antibody.
AB  - The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the
      glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a
      subject with Waldenstrom's macroglobulinaemia. Dynamic light scattering was used
      to estimate the gel point and monitor the formation of an ordered hydroscopic gel
      of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and
      organs, the associated swelling and damage to microvasculature can result in
      considerable morbidity and mortality. The three-dimensional structure of the
      branched N-linked oligosaccharide associated with the CH1 domain (first constant
      domain of heavy chain) is reported. The carbohydrate may act to shield part of
      the lateral surface of the CH1 domain and crowd the junction between the CH1 and
      CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact
      Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the
      properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque,
      Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol.
      Chem. 279, 39611-39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick,
      Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo
      protein displayed the ability to cleave, by a nucleophilic mechanism, the amide
      bonds of a variety of serine protease substrates and the gp120 coat protein of
      HIV. An atypical serine, arginine and glutamate motif is located in the middle of
      the Yvo antigen-binding site and displays an overall geometry that mimics the
      classical serine, histidine and aspartate catalytic triad of serine proteases.
      Our present findings indicate that pre-existing or natural antibodies can utilize
      at least one novel strategy for the cleavage of peptide bonds.

PMID- 16422680
TI  - Attitudes of nursing staff in general medical wards towards activation of stroke
      patients. 1981.

PMID- 16422683
TI  - Evaluating handwashing technique. 1985.

PMID- 16422691
TI  - Putting nursing research findings into practice: research utilization as an
      aspect of the management of change. 1989.

PMID- 16422687
TI  - Being old does not always mean being sick: perspectives on conditions of health
      as perceived by British and American elderly. 1987.

PMID- 16422694
TI  - Beyond empathy: expanding expressions of caring. 1991.

PMID- 16422698
TI  - Establishing rigour in qualitative research: the decision trail. 1993.

PMID- 16422701
TI  - Is the professional code still the cornerstone of clinical nursing practice?
      1995.

PMID- 16422705
TI  - Protective steering: a grounded theory study of the processes by which midwives
      facilitate informed choices during pregnancy. 1998.

PMID- 16422708
TI  - Psychiatric diagnosis: some implications for mental health nursing care. 1999.

PMID- 16422710
TI  - Music improves sleep quality in older adults. 2004.

PMID- 16422713
TI  - Discursive practices in the documentation of patient assessments.
AB  - AIM: This paper reports a study analysing the various functions of nurses'
      documentation of patient assessments. BACKGROUND: Modes of documentation have
      received much attention in the nursing press since the integration of the nursing
      process and nursing models. Previous research has shown that current
      documentation practices do not consistently promote effective communication and
      evaluation of patient care. A recent systematic review found no evidence that any
      particular system of documentation improved this situation. However, nurses'
      documentation serves not only to communicate information to others, but also has
      a political function as a presentation of what is important and ethically 'right'
      to report. METHOD: A Foucauldian approach to discourse analysis was used to
      analyse 45 patient records. FINDINGS: The findings indicate that nurses employ
      three discernible discursive practices in the documentation of patient
      assessments: medical, nursing and informal. Each practice has an effect on the
      presentation of nursing in the documentation. Because of the complex interplay
      between these practices, nurses present themselves as aligned with the medical
      profession, as distinct and professional, and as informal in their descriptions
      of non-biological information. The use of these practices appears to be motivated
      by the type of information being reporting. CONCLUSION: Existing literature
      highlights the functional aspects of nursing documentation. In contrast, this
      paper explores the way in which nurses, through their documentation, constitute
      themselves and the nursing profession. In this way, nursing documentation is
      viewed as a social practice and a conduit through which particular power effects
      are produced and reproduced, rather than simply a matter of, for example,
      knowledge, individual choice or good practice.

PMID- 16422714
TI  - Client-centred empowering partnering in nursing.
AB  - AIM: This paper explores nurses' experiences 1 year after an organization's
      commitment to providing a client-centred and client-empowering partnering
      approach to care. BACKGROUND: Historically, nurses' approach to providing care in
      all nursing contexts has been one of doing for clients, and previous studies have
      focused more on in-hospital care than on home care. However, the isolation
      inherent in in-home nursing and nurses' limited professional autonomy and power
      associated with physician control over patients in home care have been reported,
      as has their difficulty in finding the meaning and satisfaction of human
      connectedness and mutuality in nurse-client relationships. Overall, research to
      date does not inform us about how nurses might make a change toward a more client
      centred and client-empowering approach to nursing. METHODS: An interpretive
      phenomenological design was used to elicit in-depth understanding about
      Registered Nurses' experiences of providing care using this innovative
      empowerment model. A purposefully selected sample of eight Registered Nurses
      participated in in-depth interviews. Data were generated during 2002. Hermeneutic
      analysis was used to elicit themes and patterns emerging from the data. FINDINGS:
      Caring, client-centredness and the context of in-home care were important in
      implementing the new partnering approach. Barriers encountered at system,
      organizational and personal levels distracted nurses from fully comprehending and
      enacting the approach. After a year, they had begun to contemplate potential
      strategies for partnering with clients, but had not yet explored the power of
      their professional autonomy. CONCLUSION: Nurses are inclined to practise within
      the expert model of service delivery. They need to work through issues of
      professional autonomy and rise to the challenge of exercising their autonomy
      within the current healthcare context if they are to attend more consistently to
      client-centred empowering partnering. The home care setting offers an excellent
      environment for achieving these aims.

PMID- 16422715
TI  - Nurses' perceptions of quality end-of-life care on an acute medical ward.
AB  - AIM: This paper reports the findings of a study that generated a conceptual model
      of the nursing behaviours and social processes inherent in the provision of
      quality end-of-life care from the perspective of nurses working in an acute care
      setting. BACKGROUND: The majority of research examining the issue of quality end
      of-life care has focused on the perspectives of patients, family members and
      physicians. The perspective of nurses has generally received minimal research
      attention, with the exception of those working within palliative or critical
      care. The vast majority of hospitalized patients, however, continue to be cared
      for and die on medical units. To date, little research has been conducted
      examining definitions and determinants of quality end-of-life care from the
      perspective of nurses working in acute adult medical settings. METHOD: Grounded
      theory method was used in this study of 10 nurses working on acute medical units
      at two tertiary university-affiliated hospitals in central Canada. Data were
      collected during 2002 by interview and participant observation. FINDINGS: The
      basic social problem uncovered in the data was that of nurses striving to provide
      high quality end-of-life care on an acute medical unit while being pulled in all
      directions. The unifying theme of 'Creating a haven for safe passage' integrated
      the major sub-processes into the key analytic model in this study. 'Creating a
      haven for safe passage' represents a continuum of behaviours and strategies, and
      includes the sub-processes of 'facilitating and maintain a lane change'; 'getting
      what's needed'; 'being there'; and 'manipulating the care environment'.
      CONCLUSION: The ability of nurses to provide quality end-of-life care on an acute
      medical unit is a complex process involving many factors related to the patient,
      family, healthcare providers and the context in which the provision of end-of
      life care takes place.

PMID- 16422716
TI  - Profiles of pain after day surgery: patients' experiences of three different
      operation types.
AB  - AIM: The aim of this paper is to examine the pain profile of three types of day
      surgery operation and undertake a comparative analysis of the intensity and
      duration of pain over a consecutive 4-day period. BACKGROUND: Although studies on
      pain after day surgery have figured prominently, evidence is limited as to what
      intensity and duration of pain should be regarded as unacceptable, and how it
      varies for different operation types. METHODS: A prospective postal survey (n =
      785) was undertaken during a 12-month period in 1998/1999 involving three day
      surgery units in three different areas in England and Wales and based on three
      commonly performed operation types: hernia repair, varicose vein surgery and
      laparoscopic sterilization. A visual analogue scale was used to measure the
      intensity of pain experienced over a 4-day consecutive time period. Analysis of
      variance was used to explore statistically significant differences between levels
      of pain for the operation types. RESULTS: On the day of surgery and even on the
      third postoperative day, high levels of severe pain (>50 mm on a Visual Analogue
      Scale) were experienced. Pain levels differed across different operation types.
      On the day of surgery, more patients undergoing laparoscopic sterilization
      experienced severe pain. By the third postoperative day, more of those who had
      been operated on for hernia repair, followed by varicose vein surgery and
      laparoscopic sterilization, continued to experience severe pain. CONCLUSION: A
      large number of patients experienced severe levels of pain after day surgery.
      This could have resulted from a lack of knowledge about the assessment and
      management of pain, in which nurses play an important role. This study has
      highlighted that different pain trajectories are associated with different
      operation types, and this has important implications for the preoperative and
      postoperative preparation of day surgery patients as well as the role of nurses
      in the overall success of the day surgery process.

PMID- 16422717
TI  - Patients' assessments of consulting a nurse practitioner: the time factor.
AB  - AIM: This paper reports a study exploring patients' views about consulting with a
      primary care nurse practitioner. BACKGROUND: United Kingdom based randomized
      controlled trials comparing the work of doctors and nurse practitioners add
      considerable weight to the view that patients tend to be more satisfied with
      primary care nurse practitioner consultations. However, there is a need for
      qualitative research to explore issues raised by the trials. METHODS: A judgement
      sample of 10 patients consulting with a primary care nurse practitioner was
      drawn. In-depth interviews were conducted and analysed thematically. The data
      were collected in 2000-2001. FINDINGS: The following themes were identified in
      the data: time spent in the consultation; and time as a commodity in patients'
      lives. Time matters to patients when they consult on their health, whether it is
      time to discuss problems or time saved as a result of having issues resolved,
      thus minimizing further visits. Factors associated with the style and emphasis of
      consultations are also important. CONCLUSIONS: Understanding the relationship
      between time, and style and emphasis of consultation may help to explain
      patients' satisfaction with primary care nurse practitioners.

PMID- 16422718
TI  - Caring for patients living with AIDS: knowledge, attitude and global level of
      comfort.
AB  - AIMS: This paper reports a study that aimed to determine Nigerian nurses'
      knowledge, attitudes and overall level of comfort in giving nursing care to
      acquired immune deficiency syndrome patients; determine the relationship between
      these variables; and identify the sociodemographic variables that influence
      nurses' attitudes and how comfortable they are giving nursing care to patients
      with acquired immune deficiency syndrome. BACKGROUND: There is little information
      on sub-Saharan African nurses' knowledge, attitude and feeling of comfort in
      providing care to patients living with acquired immune deficiency syndrome.
      METHODS: Two hundred and seventy-seven nurses in two teaching hospitals and two
      general hospitals in Nigeria were surveyed in 2003. The survey questionnaire had
      two parts. Part I elicited demographic information and information on previous
      encounters with acquired immune deficiency syndrome patients and Part II
      consisted of three subscales assessing knowledge, attitude and level of comfort
      administering certain nursing procedures to acquired immune deficiency syndrome
      patients. RESULTS: Respondents demonstrated low levels of knowledge and poor
      attitudes towards people with acquired immune deficiency syndrome. Attitudes
      appeared to be influenced by the nurse's speciality, rank, prior education and
      experience with patients with acquired immune deficiency syndrome. The responding
      nurses showed low levels of comfort in giving care to patients with acquired
      immune deficiency syndrome. CONCLUSIONS: The findings suggest that Nigerian
      nurses will hesitate to care for patients with acquired immune deficiency
      syndrome, and that there is potential for avoidance behaviour towards them.
      Periodic continuing education and curriculum enhancement to include clinical
      clerkship, structured experience, guided discussion on ethical scenarios and
      attitude exploration are suggested in order to achieve and maintain adequate
      knowledge and a positive attitude. University-based professional and
      postprofessional nursing education, which could enhance acquisition of a broad
      knowledge base, therefore represents the future direction.

PMID- 16422719
TI  - Consulting the oracle: ten lessons from using the Delphi technique in nursing
      research.
AB  - AIM: The aim of this paper was to provide insight into the Delphi technique by
      outlining our personal experiences during its use over a 10-year period in a
      variety of applications. BACKGROUND: As a means of achieving consensus on an
      issue, the Delphi research method has become widely used in healthcare research
      generally and nursing research in particular. The literature on this technique is
      expanding, mainly addressing what it is and how it should be used. However, there
      is still much confusion and uncertainty surrounding it, particularly about issues
      such as modifications, consensus, anonymity, definition of experts, how 'experts'
      are selected and how non-respondents are pursued. DISCUSSION: This issues that
      arise when planning and carrying out a Delphi study include the definition of
      consensus; the issue of anonymity vs. quasi-anonymity for participants; how to
      estimate the time needed to collect the data, analyse each 'round', feed back
      results to participants, and gain their responses to this feedback; how to define
      and select the 'experts' who will be asked to participate; how to enhance
      response rates; and how many 'rounds' to conduct. CONCLUSION: Many challenges and
      questions are raised when using the Delphi technique, but there is no doubt that
      it is an important method for achieving consensus on issues where none previously
      existed. Researchers need to adapt the method to suit their particular study.

PMID- 16422720
TI  - Issues in data generation using email group conversations for nursing research.
AB  - AIM: The purpose of this paper is to provide an overview of the issues we have
      confronted when generating and analysing dialogue data by using electronic mail.
      BACKGROUND: The decision to use email for our research arose from our developing
      understanding of some of the consequences of illness that people living with
      chronic illness confront in their lives. As researchers, we recognized the
      potential of the Internet for computer-mediated communication using email for
      communication between researchers and research participants. DISCUSSION: We
      consider the functional aspects of generating data by email, such as the software
      needed, and then explore the issues encountered during the research process
      including ethical considerations, fluctuating participation, participants'
      familiarity with using email, facilitating lurkers towards participation,
      establishing group norms, and the role of the facilitator. CONCLUSION: As a
      collaborative inquiry, email conversation allowed us to spend time with
      participants over 2 years to explore chronic illness experience. However the
      scope and viability of computer-mediated communication as a qualitative method of
      research remains relatively unexplored, hence this paper.

PMID- 16422721
TI  - Nurses' attitudes towards adult patients who are obese: literature review.
AB  - AIMS: This paper presents a review of all empirical studies focusing on nurses'
      attitudes towards adult overweight or obese patients, with the aim of clarifying
      the dimensions and patterns of these attitudes and the methods by which they have
      been studied. BACKGROUND: Obesity has become a common condition and a major
      public health concern, but it is often associated with negative attitudes and
      discrimination. Nurses play a key role in providing support and care to patients
      who are obese. METHODS: Electronic searches were carried out on seven databases
      from inception to December 2004, along with hand-searching of references in
      relevant studies. The search terms were built around obesity (and related terms),
      nursing (and its branches) and attitudes (and related terms). Eleven studies met
      the inclusion criteria. Data were extracted and summarized in tabular form and
      analysed in relation to the aims of this review during January 2005. FINDINGS:
      There is relatively little research about nurses' attitudes towards obese
      patients, and the studies reviewed mostly have weaknesses of sampling and
      measurement. However, they do consistently suggest that a proportion of nurses
      have negative attitudes and beliefs, reflecting wider stereotypes within Western
      cultures. There is also a hint of a more complex mix of attitudes among nurses,
      some of which may counter the consequences of negative attitudes, but these have
      not been adequately investigated. A number of variables that influence attitudes
      of nurses can be identified, including age, gender, experience and the
      weight/body mass index of the nurse. CONCLUSION: Further research (both
      qualitative and quantitative) is needed with more rigorous sampling and, where
      appropriate, more consistency of measurement. A shift in focus towards the sets
      of attitudes (positive as well as negative) and behaviours that influence health
      service quality and outcomes for obese persons would be useful.

PMID- 16422722
TI  - Economics of home vs. hospital breastfeeding support for newborns.
AB  - AIM: This paper presents the findings of research comparing the incremental costs
      associated with the provision of home-based vs. hospital-based support for
      breastfeeding by nurse lactation consultants for term and near-term neonates
      during the first week of life. BACKGROUND: A consequence of both consumer demands
      and increasing health resource constraints is that alternative care delivery
      models for safe, efficacious and cost-effective breastfeeding programmes have
      steadily evolved. To date, the economic impact of the setting (home or hospital)
      where lactation support is delivered has received little research attention.
      METHODS: Mother-infant dyads were stratified by gestational age as term (>37
      weeks gestational age; n = 101) or near term (35-37 weeks gestational age; n =
      37) and randomized to standard hospital care and postpartum follow-up (standard
      care), or to standard hospital care plus home support from certified nurse
      lactation consultants (experimental). Data collection occurred at study entry,
      hospital discharge and at a seventh day postpartum follow-up session. Costs to
      the family (out-of-pocket and time costs) and to the healthcare system (during
      hospitalization and after hospital discharge) were measured. Total societal costs
      were defined as the sum of both family and healthcare system costs. RESULTS:
      Compared with standard hospital-based care, home support by nurse lactation
      consultants showed no statistically significant differences in either time costs
      to the family or total societal costs. Term infants who received home support had
      statistically significantly greater postdischarge system costs (P < 0.0001), with
      a trend towards lower out-of-pocket expenses to their families (P = 0.12). There
      were no statistically significant differences between the two groups in overall
      combined family and healthcare system costs. CONCLUSIONS: These results suggest
      that the cost of home lactation support programmes were comparable with the costs
      of hospital-based standard care. Breastfeeding support at home by lactation
      consultants should be considered as an option as it was no more costly than
      support from lactation consultants in the hospital setting. The findings for near
      term infants need to be interpreted with caution, given the small sample size.

PMID- 16422723
TI  - Discursive patterns in multiprofessional healthcare teams.
AB  - AIM: The aim of this paper is to report a study exploring how members of
      multiprofessional healthcare teams talk about their team. Specifically, the team
      members' talk was analysed to explore the discursive patterns that emerged and
      their functions. BACKGROUND: Over recent decades there has been an increasing
      demand in Western countries to change care organizations and to coordinate
      resources and professional competencies to meet the needs of patients/service
      users better. Because society promotes this kind of work, it may be valuable to
      explore the self-presentations of a multiprofessional healthcare team. METHODS: A
      discourse analysis was carried out on existing empirical data from focus group
      interviews with a member-identified category sample comprising 32 healthcare
      professionals in six authentic multiprofessional teams in south-east Sweden. The
      analysis focused on the participants' discursive constructions of
      multiprofessional teamwork, on the way they talked about their group, and, in
      particular, on their use of the pronouns we, they and I. FINDINGS: The
      constructions of 'we' by multiprofessional healthcare teams showed discursive
      patterns that are here referred to as knowledge synergy and trusting support,
      which included factors such as cross-learning and personal chemistry. The pronoun
      we was also used as a flexible resource to manage expertise, power and leadership
      within the teams, and it might also function to ease the pressure for consensus.
      CONCLUSION: These discursive patterns provided powerful rhetorical resources for
      team members, both to affirm their choice of membership and to claim superiority
      in relations with the surrounding community (the others) by linking to a societal
      discourse that promotes collaboration.

PMID- 16422729
TI  - Burn injuries in small children, a population-based study in Sweden.
AB  - AIMS AND OBJECTIVES: The aim of this study was to describe characteristics in
      burn injuries in children (zero to six years old), consulting primary care and
      hospital-based care in Malmo, Sweden. Burn-injured children consulting the
      University Hospital or the 21 Health Centres, during year 1998 and year 2002,
      were included. BACKGROUND: Epidemiological studies of burns in children have
      mostly been hospital-based and the cases that never reached the hospital have
      been excluded. DESIGN: The study had a retroperspective design with data
      collected from medical records. METHODS: Chi-squared test was used to analyse
      differences in nominal data and cross tables were used to analyse the proportions
      between the characteristics of the injuries and sex, age and nationality.
      RESULTS: The burn-injured children were 148 and 80% of those were scalds, caused
      by hot liquid (71%) or hot food (29%). The greatest number was boys between one
      and two years old. Children to foreign born parents were more frequently affected
      and the extent of the injuries often larger. Almost all the accidents (96%)
      occurred in home environment, while a family member was next to the child. The
      Health Centres received more often children affected on hand/arm and by causes
      like hot food than the University Hospital. CONCLUSIONS: Our data demonstrate the
      importance of developing a programme for the prevention of paediatric scalds with
      education of family members to be aware of the danger. With present study the
      knowledge about the occurrence of injuries in scald accidents in children has
      become deeper. This knowledge may contribute to more individual adept child
      accident prevention programme, to use in the child health care.

PMID- 16422730
TI  - An evaluation of the role of the clinical education facilitator.
AB  - AIMS AND OBJECTIVES: The objective of the study was to identify whether clinical
      education facilitators made a difference to the learning experiences of nurses in
      a large teaching hospital. BACKGROUND: Strategies for enabling continuous
      professional development are well established in health care organizations as key
      components of approaches to lifelong learning. The benefits of continuous
      professional development include the maintenance of high standards of care, the
      improvement and development of services, ensuring the competency of all nursing
      staff and guaranteeing the accountability of nurses for their actions. The role
      of clinical education facilitator is relatively new and little evaluation of this
      role has been undertaken. CONCLUSIONS: This study highlights important issues to
      be considered in developing a 'learning culture' in a hospital organization,
      through the adoption of such roles as clinical education facilitators. Whilst the
      roles have had an important function in the active coordination of learning
      activities in the hospital, there is little evidence of the role directly
      impacting on the learning culture of clinical settings. Learning mechanisms have
      been identified. The results of this evaluation can be subjected to further
      testing through ongoing evaluation of the outcomes arising from the learning
      mechanisms in place. Given the emphasis on work-based learning and continuing
      professional development in health care, then this ongoing evaluation can yield
      important information about future directions for nurse education. RELEVANCE TO
      CLINICAL PRACTICE: The study highlights the importance of supported learning in
      the workplace. However, more importantly, it identifies the need for a culture of
      professional practice to be developed in order to sustain learning in practice.
      Classroom-based learning alone, cannot create a culture of development in nursing
      and there is thus a need for models of work-based learning to be integrated into
      practice environments.

PMID- 16422731
TI  - Chest drain removal pain and its management: a literature review.
AB  - AIMS AND OBJECTIVES: The purpose of this review was to analyse critically the
      published research on chest drain removal pain and its management. The findings
      of descriptive and non-pharmacological intervention studies were summarized and
      studies of analgesic efficacy were critiqued in depth. BACKGROUND: The removal of
      a chest drain is a painful and frightening experience, particularly for children.
      However, there is limited research regarding the amount of pain experienced or
      effectiveness of analgesia for this procedure. RESULTS: Fourteen studies were
      reviewed, including five descriptive studies; three studies of non
      pharmacological interventions; and six randomized controlled trials of morphine,
      local anaesthetics and Entonox. The search revealed only two paediatric studies.
      Many of the studies had design limitations or were poorly reported. The majority
      of studies indicated that patients experienced moderate to severe pain during
      chest drain removal, even when morphine or local anaesthetics were given.
      CONCLUSIONS: Morphine alone does not provide satisfactory analgesia for chest
      drain removal pain. Non-steroidal anti-inflammatory drugs, local anaesthetics and
      inhalation agents may have a role to play in providing more effective analgesia
      for this procedure. RELEVANCE TO CLINICAL PRACTICE: Analgesic protocols for the
      management of painful procedures such as chest drain removal are unsatisfactory
      and practice in this area should be revised. More research is needed to determine
      the efficacy of drugs other than morphine, particularly Entonox and to
      investigate multi-modal techniques of management further.

PMID- 16422732
TI  - Using clinical skills laboratories to promote theory-practice integration during
      first practice placement: an Irish perspective.
AB  - AIMS AND OBJECTIVES: This aim of this study was designed to investigate how a
      select cohort of nursing students experienced their first practice placement in a
      large Irish teaching hospital. The objectives of this study were to investigate
      whom do students learn from, what skills they learnt during their first practice
      placement and to identify if the use of clinical skills laboratories before their
      first practice placement helped students relate theory to practice during their
      first practice placement. The aim of this paper is to discuss if the sessions
      taught in the clinical skills laboratory prior to the first placement helped
      students integrate theory to practice during their first practice placement.
      BACKGROUND: The debate regarding theory-practice integration has been ongoing in
      nursing for decades. Many studies across Europe have consistently demonstrated
      that the use of clinical skills laboratories have helped students integrate
      theory to practice during practice placements. Others have identified the
      difficulty students have relating theory to practice. However, as there appears
      to be a gap in current literature, from an Irish perspective, it is essential to
      highlight if Irish students can integrate theory to practice during their first
      practice placement. DESIGN: A qualitative method incorporating the Heideggarian
      approach of phenomenology was utilized. METHODS: A purposeful sampling technique
      was used to select six participants from all first year students. Interviews were
      conducted using a semi-structured interview schedule. Data were analysed using
      the Giorgi method of analysing phenomenological data. RESULTS: The participants
      identified that sessions taught in the clinical skills laboratory before the
      first practice placement, which they identified as 'basic nursing skills such as
      taking and recording vital signs and hygiene needs of patients were useful and
      helped them to integrate theory to practice during their first practice
      placement. These results are relevant to this paper as they identify the use of
      teaching sessions in the clinical skills laboratories, enabling students to link
      theory to practice during practice placements. CONCLUSIONS: Nursing students must
      be adequately prepared to carry out clinical skills competently and efficiently.
      Educators and practitioners must display the knowledge and skills required to
      promote theory-practice integration, to enhance nursing students education, which
      in turn will optimize high standards of patient care. Relevance to clinical
      practice. Clinical skills laboratories are essential to help students develop the
      collaborative skills required for a profession like nursing. It is essential that
      students are adequately prepared to carry out clinical skills during their first
      practice placement, and have the ability to link theory to practice.

PMID- 16422733
TI  - A 4-cm thermoactive viscoelastic foam pad on the operating room table to prevent
      pressure ulcer during cardiac surgery.
AB  - AIMS AND OBJECTIVES: In this experimental study, a 4-cm thermoactive viscoelastic
      foam overlay and a heating source on the operating room table was compared with
      the standard operating room table with a heating source for the effect on the
      postoperative pressure ulcer incidence in cardiac surgery patients. BACKGROUND:
      Pressure ulcer incidence in the cardiac surgery population is reported to be up
      to 29.5%. The prolonged compressive forces from lying on the operating room table
      are one source of pressure ulcer development in this population. Pressure
      reducing devices on the operating room (OR)-table should reduce the patients'
      interface pressure and thus the hazard of skin breakdown. METHODS: A randomized
      controlled trial was performed to test the effect of a 4-cm thermoactive
      viscoelastic foam overlay with a water-filled warming mattress on the OR-table
      (test OR-table) compared with the standard OR-table (a water-filled warming
      mattress, no pressure-reducing device) on the postoperative pressure ulcer
      incidence in cardiac surgery patients. INSTRUMENTS: The pressure ulcer
      classification system of the European Pressure Ulcer Advisory Panel (EPUAP) was
      used for pressure ulcer grading. RESULTS: The results show that patients lying on
      the 4-cm thermoactive viscoelastic foam overlay suffer slightly more pressure
      ulcer (17.6%) than patients on the standard OR-table without the foam overlay
      (11.1%). Because of the clinical relevance of the results, the randomized
      controlled trial was terminated after 175 patients at the interim analysis
      although the power calculation stated 350 patients. CONCLUSIONS: The combination
      of a 4-cm viscoelastic foam overlay and a warming source cannot be recommended
      for pressure ulcer prevention on the operating room table. RELEVANCE TO CLINICAL
      PRACTICE: Foam overlays are used to prevent pressure ulcers in patients. It is
      necessary to use such devices according to patient safety and use of resources.

PMID- 16422734
TI  - Nutrition of the critically ill patient and effects of implementing a nutritional
      support algorithm in ICU.
AB  - AIM: To test whether a feeding algorithm could improve the nutritional support of
      intensive care patients. BACKGROUND: Numerous factors may impede delivery of both
      enteral and parenteral nutrition to patients in the intensive care unit. Often
      there is a discrepancy between what is prescribed and actual delivery of
      nutrients. The purpose of this study was to test the effect of a nutritional
      support algorithm in an intensive care unit mainly by using the enteral route and
      if necessary by combining enteral and parenteral nutrition. METHODS: In this
      prospective study, nutritional data were collected from routinely fed critically
      ill patients (controls, n=21) during the first three days following admission to
      the intensive care unit. A nutritional support algorithm was then implemented and
      nutritional data were collected from critically ill patients who participated in
      this intervention (intervention group, n=21). Data collected included the total
      amount of calories prescribed vs. received, onset of delivery of enteral
      nutrition, enteral vs. parenteral nutrition, and the use and size of enteral
      feeding tubes. RESULTS: Patients in the intervention group were both prescribed
      and actually received significantly larger amounts of nutrients than patients in
      the control group. They also received a larger proportion of their nutrients in
      the form of enteral nutrition. In addition, the nutritional support algorithm led
      to greater consistency in nursing practices with respect to aspiration of gastric
      content and rate of increment in enteral feeding. CONCLUSION: The study confirms
      that a nutritional support algorithm improved the delivery of nutrients to
      critically ill patients. The algorithm was most effective with respect to the
      delivery of enteral nutrition. The effect was primarily because of early and more
      rapid increment in the delivery of enteral nutrition administered by nurses based
      on improved physician orders. The combination of enteral and parenteral nutrition
      may contribute to meeting adequate nutritional requirements. RELEVANCE TO
      CLINICAL PRACTICE: By using a nutritional algorithm focused on enteral nutrition,
      but including parenteral nutrition as a supplement, it is possible to improve the
      delivery of clinical nutrition in the intensive care unit patients.

PMID- 16422735
TI  - Use of technological equipment in critical care units: nurses' perceptions in
      Greece.
AB  - AIMS AND OBJECTIVES: The aim of this study was to determine the perceptions of
      nurses who work in critical care units about positive and negative effects
      related to the use of technological equipment and identify relationships between
      these perceptions and demographic characteristics of participants. BACKGROUND:
      Previous researchers have investigated the perceptions of nursing personnel about
      the effects of technology on clinical practice. However, most of them focus on
      specific negative effects. Positive and negative effects have never been studied
      as a whole. DESIGN: Critical care nurses were surveyed to elicit their
      perceptions regarding the use of technological equipment. The instrument
      comprised a 14-item questionnaire and a series of demographic characteristics. A
      five-point Likert scale was used for each of these 14 questions. METHODS: The
      questionnaire was administered to 122 nurses working at the four critical care
      units of a major academic hospital in Patras, Greece, from 1/10/2003 to
      31/12/2003. The completion of the questionnaires was achieved by means of a
      personal interview. RESULTS: A total of 118 questionnaires were completed. The
      majority of nurses recognized the positive effects of equipment regarding patient
      care and clinical practice. At the same time, they agreed that use of equipment
      possibly leads to increased risk due to human errors or mechanical faults,
      increased stress and restricted autonomy of nursing personnel. CONCLUSIONS: The
      use of machines does not add to nursing prestige and this may be related to
      decreased autonomy. Human errors, mechanical faults and increased stress do not
      seem to come as a result of time constriction but rather of inadequate education.
      Undergraduate and continuing education should respond efficiently to the needs of
      contemporary critical care. RELEVANCE TO CLINICAL PRACTICE: Recognition of
      positive and negative effects of machines through the investigation of
      perceptions of nurses is the first step before looking for ways of maximizing
      advantages and facing disadvantages of equipment use.

PMID- 16422736
TI  - Caring in nursing: investigating the meaning of caring from the perspective of
      cancer patients in Beijing, China.
AB  - AIMS: The aims of the study were to develop an understanding of caring in nursing
      from the perspective of cancer patients and attempt to identify the concept of
      caring in the Chinese cultural context. BACKGROUND: Caring as a concept remains
      elusive, the acceptable definitions of the term care have not been reached. The
      expressions, processes and patterns of caring vary among cultures, but there is a
      lack of Chinese culture-based study about caring in nursing. METHODS: A
      qualitative research design was used and 20 cancer patients were interviewed
      using a semi-structured interview guide. A qualitative content analysis was used
      to identify themes in the data. RESULTS: Three themes emerged from the data,
      which suggested that caring is delivering care in an holistic way: nurses' caring
      attitudes and their professional responsibility for providing emotional support,
      nurses' professional knowledge and their professional responsibility for
      providing informational support and nurses' professional skills and their
      professional responsibility for providing practical support. The caring behaviour
      of nurses as perceived by cancer patients involved the provision of emotional,
      informational, and practical support and help based on patients' needs. A model
      of caring in nursing was formulated. CONCLUSIONS: Caring in nursing as perceived
      by cancer patients involves nurses having qualified professional knowledge,
      attitudes and skills in oncology and providing the informational, emotional and
      practical supports and help required by cancer patients. RELEVANCE TO CLINICAL
      PRACTICE: Caring is manifested in nursing actions through nurse-patient
      communication process. Patients have their inner expectation for nurses' caring
      behaviour and attitudes and nurses' performance of caring or uncaring behaviour
      has a direct influence on the feelings of patients. It is necessary for all
      nurses to continue improving their oncology professional knowledge, attitudes and
      skills as well as their abilities of offering informational, emotional and
      practical support and help for their cancer patients.

PMID- 16422737
TI  - Exploring community nurses' perceptions of life review in palliative care.
AB  - AIMS AND OBJECTIVES: This exploratory study aimed to identify community nurses'
      understanding of life review as a therapeutic intervention for younger people
      requiring palliative care. The objectives set out to: (i) Describe the
      participants' understanding of reminiscence and life review (ii) Detail their
      current ideas regarding a structured approach to using life review in the
      community setting. (iii) Outline their understanding of the possible advantages
      and limitations of life review in relation to palliative care. (iv) Identify
      future training requirements. BACKGROUND: The literature review illustrated how
      the eighth developmental stage of Erikson's theory, ego-integrity vs. despair, is
      a 'crisis' often faced by older people entering the final stage of life. Life
      review is considered a useful therapeutic intervention in the resolution of this
      crisis. Younger terminally ill people in the palliative stage of an illness may
      face the same final crises due to their reduced lifespan. Therefore, this study
      explored the benefits and limitations of life review as an intervention in
      palliative care. METHOD: The study used a purposive sample of community nurses
      responsible for delivering generic and specialist palliative care. A qualitative
      method of data collection in the form of three focus group interviews was used.
      Subsequent data were manually analysed, categorized and coded with associations
      between the themes identified. RESULTS: The findings suggested that community
      nurses have limited knowledge pertaining to the use of life review and tend to
      confuse the intervention with reminiscence. Furthermore, they believed that life
      review could potentially cause harm to practitioners engaged in listening to
      another person's life story. However, the participants concur that with
      appropriate training they would find life review a useful intervention to use in
      palliative care. CONCLUSIONS: The results led to the identification of a number
      of key recommendations: Community nurses require specific education in the
      technicalities of life review and additional interpersonal skills training. The
      need for formalized support through clinical supervision is also recognized and
      discussed. Finally, suggestions are offered regarding the need to generate wider
      evidence and how, possibly, to integrate life review into existing palliative
      care services. RELEVANCE TO CLINICAL PRACTICE: This study has demonstrated that
      community nurses are keen to extend the support offered to younger terminally ill
      people who are in the palliative stage of their illness. Despite having limited
      knowledge of life the main components and underpinning theory pertaining to life
      review participants could appreciate the potential of life review as a
      therapeutic intervention in palliative care and were keen to learn more about its
      use and gain the necessary knowledge and skills.

PMID- 16422738
TI  - Structured reminiscence: an intervention to decrease depression and increase self
      transcendence in older women.
AB  - AIMS/OBJECTIVES: The purpose of this study was to assess the effect of group
      reminiscing on depression and self-transcendence of older women residing in an
      assisted living facility in southeast Texas. There were two major objectives for
      this study. One objective was to determine if depression decreased in older women
      after structured reminiscence group sessions held twice weekly for a six-week
      period. A second objective was to determine if self-transcendence increased after
      structured reminiscence group sessions held twice weekly for a six-week period.
      BACKGROUND: Reminiscence has been studied to determine its impact on a variety of
      conditions including but not limited to depression, self-esteem, fatigue,
      isolation, socialization, well-being, language acquisition and cognitive
      functioning. This review of research specifically focused on reminiscence,
      depression, self-transcendence and older people. DESIGN/METHODS: Two groups were
      assessed at baseline, three and six weeks to answer the research questions. A
      sample of 24 women between the ages of 72 and 96 years were randomly assigned to
      either a reminiscence (experimental) group or the activity (control) group of the
      facility. Pearson's r was used to determine the magnitude of the relationship
      between subjects' responses on the Geriatric Depression Scale and the Self
      Transcendence Scale. A mixed design analysis of variance (anova) was used to
      determine if there was a difference between the experimental and control groups
      on scores of the Geriatric Depression Scale and the Self-Transcendence Scale at
      baseline, three and six weeks. CONCLUSIONS: Data revealed a non-significant
      decrease in depression and increase in self-transcendence in the reminiscence
      group at the completion of six weeks, indicating a trend toward a positive result
      with reminiscence group sessions. The study also revealed an inverse relationship
      between depression and self-transcendence. These findings underscore the
      importance of screening older people for depression. RELEVANCE TO CLINICAL
      PRACTICE: One of the primary modalities used for the treatment of depression in
      elderly women is medication. Antidepressant medications lead to harmful side
      effects without alleviating the underlying depression. For these reasons, there
      is a need to research alternative therapies for treatment of depression in the
      older female. Reminiscence offers a possible intervention for treatment of
      depression in older women.

PMID- 16422739
TI  - The health promotion model as assessed by ageing workers.
AB  - AIMS: This study describes qualitatively ageing workers and their health
      promotion. It also describes quantitatively the importance of individual,
      workplace and occupational health promoting factors, the impact of health
      promotion and the contributions of the other co-partners promoting the health of
      ageing workers. These form the foundation for a model of health promotion.
      BACKGROUND: Very little is known about the health promotion factors exclusively
      focused at ageing workers. METHODS: A pretested questionnaire with structured and
      some open-ended questions were devised to form the basis of qualitative data and
      sent to 150 ageing workers, of whom 93 (62%) returned it. Qualitative data were
      analysed by content analysis. Statistical analyses were performed using
      frequencies and means. RESULTS: Over 90% of respondents stated that health
      habits, individual arrangements at the workplace, a good workplace spirit, health
      checks, counselling and access to nursing care were important factors for health
      promotion. Better health (99%), work satisfaction (95%) and motivation of
      employees (96%) were the factors impacting on health promotion. Ageing workers
      stated that health and safety organization (94%) and rehabilitation institutes
      (93%) were the most important co-partners. CONCLUSIONS: This study confirms
      extremely high importance of different health promotion factors, their impact and
      some co-partners. Health problems, early retirement and work absenteeism are
      rather common in ageing workers. If we are to avoid these problems, it is
      important to support their work ability effectively and systematically to allow
      these workers to stay employed until the normal retirement age. Relevance to
      clinical practice. It is necessary, that management appreciate the benefits of
      ageing workers; they have to take a positive attitude toward these workers and
      participate more effectively in their health promotion. Occupational health
      professionals play a key role in training workers and management to undertake the
      required measures.

PMID- 16422740
TI  - Knowledge, health beliefs, and behaviours in first-degree relatives of women
      suffering from osteoporosis.

PMID- 16422741
TI  - Commentary on Whitehead D (2004) Health-promoting hospitals: the role and
      function of nursing. Journal of Clinical Nursing 14, 20-27.

PMID- 16422743
TI  - Commentary on Whittemore R, Melkus GD & Grey M (2005) Metabolic control, self
      management and psychosocial adjustment in women with type 2 diabetes. Journal of
      Clinical Nursing 14, 195-203.

PMID- 16422744
TI  - Darbyshire P (2004) 'Rage against the machine?': Nurses' and midwives'
      experiences of using computerized patient information systems for clinical
      information. Journal of Clinical Nursing 13, 17-25.

PMID- 16422745
TI  - Commentary on Schultz PN, Klein MJ, Beck ML, Stava C & Sellin RV (2005) Breast
      cancer: relationship between menopausal symptoms, physiologic health effects of
      cancer treatment and physical constraints on quality of life in long-term
      survivors. Journal of Clinical Nursing 14, 204-211.

PMID- 16422746
TI  - Commentary on Defloor T & Grypdonck MFH (2005) Pressure ulcers: validation of two
      assessment scales. Journal of Clinical Nursing 14, 373-382.

PMID- 16422747
TI  - Commentary on Glacken M & Chaney D (2004) Perceived barriers to implementing
      research findings in the Irish practice setting. Journal of Clinical Nursing 13,
      731-740.

PMID- 16422748
TI  - Commentary on Smith L and Callery P (2005) Children's accounts of their
      preoperative information needs. Journal of Clinical Nursing 14, 230-238.

PMID- 16422749
TI  - Commentary on McKenna HP, Keeney S and Hasson F (2005) Views on the ground:
      teaching and clinical assessors' views on vocational training for health care
      assistants in Ireland. Journal of Clinical Nursing 14, 426-434.

PMID- 16422750
TI  - Commentary on Watson B, Clarke C, Swallow V and Forster S (2005) Exploratory
      factor analysis of the research and development culture index among qualified
      nurses. Journal of Clinical Nursing 14, 1042-1047.

PMID- 16422751
TI  - Orofacial/cerebral injuries and the use of mouthguards by professional athletes
      in Switzerland.
AB  - The objective of the present study was to measure the occurrence of orofacial and
      cerebral injuries in different sports and to survey the awareness of athletes and
      officials concerning the use of mouthguards during sport activities. Two hundred
      and sixty-seven professional athletes and 63 officials participating in soccer,
      handball, basketball and ice hockey were interviewed. The frequency of orofacial
      and cerebral trauma during sport practice was recorded and the reason for using
      and not using mouthguards was assessed. A great difference in orofacial and
      cerebral injuries was found when comparing the different kinds of sports and
      comparing athletes with or without mouthguards. 45% of the players had suffered
      injuries when not wearing mouthguards. Most injuries were found in ice hockey,
      (59%), whereas only 24% of the soccer players suffered injuries when not wearing
      mouthguards. Sixty-eight percentage of the players wearing mouthguards had never
      suffered any orofacial and cerebral injuries. Two hundred and twenty-four
      athletes (84%) did not use a mouthguard despite general acceptance by 150
      athletes (56%). Although the awareness of mouthguards among officials was very
      high (59%), only 25% of them would support the funding of mouthguards and 5%
      would enforce regulations. Athletes as well as coaches should be informed about
      the high risk of oral injuries when performing contact sports. Doctors and
      dentists need to recommend a more intensive education of students in sports
      medicine and sports dentistry, and to increase their willingness to become a team
      dentist.

PMID- 16422752
TI  - Prevalence and risk of traumatic gingival recession following elective lip
      piercing.
AB  - The aims of this study were to evaluate the prevalence, risk and odds ratios of
      gingival recession defects associated with elective lip piercing and wearing of
      stud jewelry, and to attempt to identify risk factors that might permit the
      incidence of recession and its severity to be predicted, using Miller's
      classification. Ninety-one subjects with lip piercing and labrets were evaluated
      with regard to gender, age, smoking history, orthodontic history, and labret
      characteristics. An age-matched group of 54 individuals without peri-oral
      piercing provided the control. Gingival recession was recorded on teeth opposing
      a labret in 68.13% of pierced subjects. By contrast, only 22.2% of unpierced
      individuals demonstrated recession. The odds ratio between pierced and control
      groups indicates a likelihood of recession 7.5 times greater in a pierced
      individual wearing a labret than in an unpierced individual. Logistical
      regression analysis showed that age, gender, smoking and labret configuration did
      not significantly influence the development of recession. Furthermore, an
      illustrative example indicates that piercing and provision of a labret might
      typically increase the risk of recession occurring from 34.4% (pre-piercing) to
      80.8 %. Recession severity was greater in the pierced group, with Miller's class
      2 and 3 defects observed in 18.7% of the pierced but not at all in the unpierced
      group. Ordinal regression identified previous orthodontic treatment as the only
      significant predictor of Miller's grade. We concluded that a clear link exists
      between lip piercing, labret use and gingival recession. Belief that labret
      placement and configuration can be modified to provide protection is unfounded.

PMID- 16422753
TI  - Long-term effect of different treatment modalities for traumatized primary
      incisors presenting dark coronal discoloration with no other signs of injury.
AB  - The aim was to compare the long-term outcomes of root canal treatment with that
      of follow-up-only in traumatized primary incisors in which dark discoloration is
      the only sign of injury. Root canal treatment was performed in 48 dark discolored
      asymptomatic primary incisors following trauma. Twenty-five of them [root canal
      treatment (RCT) group] were followed till eruption of their permanent successors.
      Ninety-seven dark discolored asymptomatic primary incisors were left untreated
      and invited for periodic clinical and radiographic examination. Of these, 28
      [follow-up (FU) group] were followed till eruption of their permanent successors.
      The parameters examined included early extraction of the traumatized primary
      incisor, early or delayed eruption of the permanent successors, ectopic eruption
      of the permanent successor and signs of enamel hypopcalcification or hypoplasia
      in the permanent successor. Chi-square test was used for statistical analysis.
      Seven of 25 (28%) of the RCT group and 32% (nine of 28) of the FU group required
      early extraction. Five of 25 (20%) of the RCT group and 21% (six of 28) of the FU
      group showed early or delayed eruption of the permanent successors. Sixteen of 25
      (64%) of the RCT group and 79% (22 of 28) of the FU group showed ectopic eruption
      of the permanent successors. Enamel hypopcalcification or hypoplasia in the
      permanent successors was equally found (36%) in both groups (nine of 25 in the
      RCT group and 10 of 28 in the FU group). None of differences was statistically
      significant. Root canal treatment of primary incisors that had change their color
      into a dark-gray hue following trauma with no other clinical or radiographic
      symptom is not necessary as it does not result in better outcomes in the primary
      teeth and their permanent successors.

PMID- 16422754
TI  - Three-dimensional bone microstructures of the mandibular angle using micro-CT and
      finite element analysis: relationship between partially impacted mandibular third
      molars and angle fractures.
AB  - The mandibular angle is one of the areas of the mandible that are prone to bone
      fractures, and the presence of an impacted third molar has been found to be
      associated with increased risk of angle fractures. The factors involved in bone
      fractures are the amount and direction of load, and the biomechanical and
      anatomical properties of bone. In the present study, micro-focused X-ray computed
      tomography was performed to observe and analyze the three-dimensional (3D) bone
      microstructure of the mandibular angle, and finite element analysis was conducted
      to examine the relationship between angle fractures and the presence or absence
      of mandibular third molars. 3D bone microstructure showed no marked difference
      between mandibles with and without third molars. Finite element analysis showed
      that, in the mandible with a third molar, stress was concentrated around the root
      apex of the third molar, and was transmitted in a direction matching the clinical
      findings of angle fractures. The results obtained in this study suggest that the
      presence of an impacted third molar changes the concentration and transmission of
      stress in the mandible, thus increasing the risk of an angle fracture.

PMID- 16422755
TI  - In vitro clonogenic capacity of periodontal ligament fibroblasts cultured with
      Emdogain.
AB  - The aim of the present study was to evaluate the efficiency of Emdogain (EMD) in
      preserving the size of the periodontal ligament progenitor pool (clonogenic
      capacity) and in promoting their proliferation. Periodontal ligament fibroblasts
      (PDLF) were obtained from explants of young permanent healthy tooth. After
      initial outgrowth (10 days to 2 weeks following explantation), the culture medium
      of experimental flasks was replaced with medium supplemented with 100 microg ml(
      1) EMD, whereas the other served as controls and were fed with regular medium.
      Following 5 weeks, the cells were washed (3x), harvested (trypsin + EDTA), and
      evaluated for their viability. Viable cells from each group were inoculated into
      six 96-well plates at a concentration of one viable cell per two wells and were
      allowed to grow for 5 weeks. The percentage of cells with clonogenic capacity was
      determined as the number of colonies formed/number of cells seeded x 100 in the
      experimental and control groups. Three degrees of dish area coverage were
      utilized: up to 25%, between 25% and 75% and higher than 75%. This experiment was
      repeated four times from four different donors. A total of 2328 cells were
      evaluated, half of which, were cultured with EMD. The mean percentage of cells
      (from all donors) who exhibited any clonogenic capacity in the presence of EMD
      was comparable with that of cells cultured in the absence of EMD: 26.6 +/- 14.3%
      when compared with 34.6 +/- 20.6% respectively (P = 0.186). Similarly, the
      percentage of clones that proliferated to cover up to 25% of the well area was
      comparable in the two groups 7.5 +/- 8.6 for EMD-treated clones and 7.1 +/- 7.8
      for untreated clones (P = 0.674). The percentage of clones that proliferated to
      cover 25% up to 75% of the well area was greater EMD-treated clones as compared
      with the untreated cells: 8.1 +/- 6.7% vs 3.8 +/- 3%. However this difference was
      not statistically significant (P = 0.277). In contrast, the percentage of clones
      that covered more than 75% of the well area was significantly lower in the EMD
      treated clones when compared with the untreated clones (10.9 +/- 11.1 vs 23.8 +/-
      14.7; P = 0.022) . In conclusion, EMD decreased the percentage of PDLF with
      capabilities of arising colonies with 75-100% confluency probably by increasing
      their differentiation.

PMID- 16422756
TI  - Evaluation of the topical effect of alendronate on the root surface of extracted
      and replanted teeth. Microscopic analysis on rats' teeth.
AB  - The treatment of choice for tooth avulsion is replantation. The ideal
      replantation should be realized as quickly as possible, or at least, the avulsed
      tooth should be kept in an adequate solution to preserve the periodontal ligament
      attached to the root. If that is not possible, treatment of the radicular surface
      should be done in order to prevent radicular resorption. The purpose of this
      study was to test sodium alendronate as a substance for topical treatment of the
      radicular surface of avulsed teeth in an attempt to prevent the occurrence of
      dental resorptions. Fifty-four rat maxillary right central incisors were
      extracted and replanted. Group I--extra-alveolar dry period of 15 min, intracanal
      dressing with calcium hydroxide (CALEN, S.S. White, Artigos Dentarios LTDA, Rio
      de Janeiro, Brazil) and replantation; Groups II and III - extra-alveolar dry
      periods of 30 and 60 min, respectively, immersion in 1% sodium hypochlorite for
      30 min for removal of the periodontal ligament, washing in saline solution for 5
      min, and treatment of the radicular surface with 3.2 mg/l sodium alendronate
      solution for 10 min. Intracanal dressing with calcium hydroxide and replantation
      followed. At 15, 60, and 90 days post-reimplantation, the animals were killed and
      the samples obtained and processed for microscopic analysis. The results
      indicated that sodium alendronate was able to reduce the incidence of radicular
      resorption, but not of dental ankylosis. No significant differences were observed
      regarding variations in the extra-alveolar periods among the groups.

PMID- 16422757
TI  - Morphometric and microscopic evaluation of the effect of solution of
      acetazolamide as an intracanal therapeutic agent in late reimplanted rat teeth.
AB  - The use of substances that inhibit root resorption may be an alternative for
      cases of unsuccessful reimplants. Hence, the purpose of this study was to test a
      solution of acetazolamide, a resorption inhibitor, as an intracanal therapeutic
      agent for late reimplanted teeth. Thirty rat maxillary right central incisors
      were avulsed and kept dry for 30 min. The teeth were instrumented, and the root
      surfaces treated with 1% hypochlorite solution followed by application of 2%
      sodium fluoride. Thereafter, the teeth were divided into two groups according to
      the intracanal dressing: Group I, solution of acetazolamide and Group II, calcium
      hydroxide paste. Teeth were then reimplanted in their respective sockets. The
      animals were killed at 15, 30, and 60 days after reimplantation and the samples
      processed for morphometric and microscopic analysis. The results showed that
      calcium hydroxide paste limited root resorption, even though not avoiding it. In
      contrast, no root resorption was observed after 60 days in the acetazolamide
      group, confirming the efficacy of the substance in inhibiting root resorption.

PMID- 16422758
TI  - Multiple dental fractures following tongue barbell placement: a case report.
AB  - The number of adolescents and young adults undergoing intra-oral piercing, is
      increasing worldwide. There have been several case reports documenting oral and
      systemic complications of this practice. These include damage to the dentition,
      gingivae, infection, speech impediments and nerve damage. The case presented here
      draws attention to the possibility of multiple tooth fracture as a result of
      trauma incurred from a barbell inserted into the tongue.

PMID- 16422759
TI  - Trauma to an osseointegrated anterior dental implant: a case report.
AB  - Single tooth implant systems have been shown to offer a safe and highly
      predictable option for the replacement of anterior teeth. There is however, a
      paucity of evidence on the result of trauma to single tooth implant systems,
      particularly in the vulnerable anterior maxillary area. This article presents a
      report on the outcome of a traumatic incident to an osseointegrated single tooth
      implant.

PMID- 16422760
TI  - Multidisciplinary approach to the rehabilitation of a crown-root fracture with
      original fragment for immediate esthetics: a case report with 4-year follow-up.
AB  - Dental practitioners frequently encounter dentoalveolar traumas. According to the
      severity of the trauma, a large spectrum of complications such as isolated tooth
      fracture, dentoalveolar fracture or fracture at maxillofacial region may occur.
      If the isolated tooth fracture occurs particularly at anterior region, the
      rehabilitation should satisfy both esthetic and functional problems. An
      unrestorable tooth should be extracted and this leads to more complex treatments
      such as implant or conventional prosthetic rehabilitations, which will restore
      the function, but impair the esthetics. Recently, powerful new generation dual
      cured resin composites have been produced for reattachment of original fractured
      fragments. In this case, we presented treatment of oblique crown-root fracture of
      a maxillary central tooth from enamel-cement junction by the reattachment
      technique. We used dual cured resin composite (Panavia F) and a self-tapping
      screw-post (Dentatus) for reattaching the crown fragment. Orthodontic treatment
      was applied for intruding and leveling the tooth. Four years after treatment, the
      tooth exhibited good esthetics, good periodontal health and normal function.
      However, minimal relapse occurred in spite of orthodontic treatment. In
      conclusion, the reattachment technique is an alternative method, which offers
      satisfactory esthetic and functional rehabilitation of the fractured teeth.

PMID- 16422761
TI  - Mandibular fracture 2 weeks after third molar extraction.
AB  - This case report describes mandibular fracture after the surgical extraction of
      fully erupted lower third molar of a 53-year-old healthy male patient. The
      fracture occurred 15 days after the extraction while chewing. The fracture line
      extended from the apex of the mesiobuccal root socket to the inferior border of
      the mandible. Follow-up of the patient was agreed as the patient was not willing
      to carry on further treatment. Bony union was observed radiologically 3 months
      later.

PMID- 16422762
TI  - Antibiotic coverage for lip wound.

PMID- 16422763
TI  - Nutritional physiology of neonatal calves.
AB  - The gastrointestinal tract of neonatal calves is relatively mature but still
      requires morphological and functional changes. The intake of colostrum with its
      nutrient and non-nutrient components exerts marked effects on gastrointestinal
      development and function. Colostrum intake provides immunoprotection (passive
      immunity by immunoglobulins) and is essential for survival of neonates of most
      species. Furthermore, there are important transient as well as long-lasting
      systemic effects on the nutritional status, on metabolism, and on various
      endocrine systems due to intake of nutrient and non-nutrient colostral components
      that contribute to survival in the stressful postnatal period. Colostrum is much
      more than just a supplier of immunoglobulins.

PMID- 16422765
TI  - Influence of the feed base excess on urine parameters in cats.
AB  - In this study the base excess (BE) was used as a method to predict the influence
      of the food on the urinary pH on cats. Nine cat foods (six dry and three canned)
      were consecutively fed to eight cats. The urine pH, volume, specific gravity and
      water and food intake were determined daily. The base excess [BE; mmol/kg dry
      matter (DM)] was calculated from the compounds in the food (BE =
      49.9*Ca+82.3*Mg*+43.5*Na+25.6*K-64.6*P-13.4*Met-16.6*Cys-28.2*Cl). The BE of the
      tested foods was between -287.35 and 133.38 mmol/kg DM. The mean urine pH varied
      between 5.76 (SD = 0.13) and 7.16 (SD = 0.22). The BE correlated with the mean
      urine pH (pH = 6.25+0.0023*BE; r = 0.74**). The urine volume (ml/kg BW/day)
      correlated significantly positive with the K- (r = 0.71**) and significantly
      negative with the P-content (r = -0.67**), the Ca-content (r = -0.50**) followed
      by the Mg-content (r = -0.36**) of the food. The correlation coefficients between
      the anions/cations in the food and the urine pH was for K 0.36**, for P -0.61**,
      the Met+Cys -0.60** and Cl -0.27**. In practice the correlation between urine pH
      and BE would help to pre-estimate the effect of food on the urine pH and to
      prevent urolith formation.

PMID- 16422764
TI  - Effect of ovariectomy and ad libitum feeding on body composition, thyroid status,
      ghrelin and leptin plasma concentrations in female dogs.
AB  - The objective of this study was to evaluate the effects of ovariectomy (i) and ad
      libitum feeding (ii) on energy intake, body weight (BW), body composition,
      thyroid status, leptin and ghrelin plasma concentrations. Four young adult female
      Beagle dogs were fed a maintenance diet for 6 weeks prior to ovariectomy, then 6
      months after. Food allowance was adjusted in order to maintain optimal BW. Then,
      a diet slightly higher in energy concentration was fed ad libitum for 4 months.
      The maintenance diet was then fed ad libitum for one additional month. The
      maintenance of optimal BW after ovariectomy required a significant decrease in
      energy allowance. No increase in fat mass was observed. Ghrelin concentration
      remained unchanged. During the first month of ad libitum feeding, plasma ghrelin
      concentration and energy intake increased, then they decreased. Mean BW, plasma
      leptin, thyrotropin (TSH), total triiodothyronine (TT3) and total thyroxine (TT4)
      concentrations significantly increased over the study. The BW increase was
      exclusively due to an increase in body fat. In conclusion, energy allowance
      should be strictly controlled in spayed female dogs. The results suggest that in
      dogs, thyroid hormones, leptin and ghrelin concentrations change in response to a
      positive energy balance in an attempt to limit weight gain. However, the
      significant weight gain shows that this goal was not achieved.

PMID- 16422766
TI  - Effects of a probiotic Enterococcus faecium strain supplemented from birth to
      weaning on diarrhoea patterns and performance of piglets.
AB  - This placebo-controlled double-blind study was conducted to evaluate effects of
      Enterococcus faecium DSM 10663 NCIMB 10415 (EcF) orally given from birth to
      weaning on diarrhoea and performance of piglets. At the first 3 days postnatum
      (p.n.), piglets from 54 [verum group (VG)] and 60 [placebo group (PG)] sows got 1
      g of a gel directly per mouth by a dosing device. Gel for the VG contained 2.8 x
      10(9) colony forming units (CFU) EcF/g. From day 4 p.n. until weaning (24 +/- 3.2
      days p.n.) a liquid additive was given that administered twice a day 1.26 x 10(9)
      CFU EcF to each VG piglet. In case of diarrhoea, an electrolyte solution was used
      which provided daily 2.9 and 5.8 (week 1 and >or= 2, respectively) x 10(8) CFU
      EcF per VG piglet. Diarrhoea scores were defined as follows: (i) no diarrhoea;
      (ii) piglets developed diarrhoea, but were vital and (iii) piglets suffered from
      diarrhoea and additionally looked pale, developed rough coat, showed slackening
      of the flank and lethargy. Counts of viable born, stillborn and weaned piglets
      were normal and not different between groups (p > 0.05). Placebo group vs. VG
      piglets suffered more frequently from diarrhoea (40.0 vs. 14.8%, p < 0.05).
      Duration of diarrhoea was not affected by feeding EcF (2.2 +/- 0.81 days, p >
      0.05). Diarrhoea score was lower in VG vs. PG (1.2 vs. 1.5 +/- 0.54, p < 0.05)
      and the daily weight gain (DWG) was higher by 17 g/day (p < 0.05). Results
      suggest that the daily oral supplementation of EcF from birth to weaning reduces
      the portion of piglets suffering from diarrhoea. This may improve performance, as
      the higher DWG indicates. In contrast, no obvious benefit seems to result from an
      additional supply of EcF via electrolyte solution when diarrhoea is always
      present.

PMID- 16422767
TI  - Effects of feeding deoxynivalenol contaminated wheat on growth performance, organ
      weights and histological parameters of the intestine of broiler chickens.
AB  - A feeding trial was conducted to evaluate the effects of moderate dietary
      concentrations of deoxynivalenol (DON) during a 21-day feeding experiment on the
      performance of broilers. Fifteen 1-day-old broiler chicks were randomly divided
      into two groups. The control group was fed non-contaminated diet. Another group
      of broilers was fed a diet naturally contaminated with 5 mg DON/kg diet.
      Deoxynivalenol had no effect (p > 0.05) on feed consumption, feed conversion,
      body-weight gain, live body weight or mortality. The absolute and relative weight
      of the organs (gizzard, pancreas, heart, spleen, colon and caecum) were not
      altered by the dietary inclusion of DON contaminated grain. However, both the
      absolute and relative weight of small intestine was decreased (p < 0.01) in DON
      fed broilers compared to the controls. No gross lesions were detected in any of
      the organs of birds fed contaminated wheat during the feeding trial. The
      microscopic examination revealed that, the height and the width of villi in
      duodenum decreased (p < 0.05) in birds fed DON contaminated wheat compared to
      controls. On the other hand the height and the width of jejunum villi were not
      affected (p > 0.05). This study indicates that feeding DON for 21 days to broiler
      chickens at a concentration of up to 5 mg/kg of diet influenced the weight of the
      small intestine as well as intestinal histology, especially the duodenum, as
      evidenced by shorter and thinner villi. In conclusion, diets with DON
      contamination below levels that induce negative impact on health and performance
      could affect small intestinal morphology in broilers.

PMID- 16422768
TI  - Late development of homoeothermy in mink (Mustela vison) kits -- a strategy for
      maximum survival rate.
AB  - The objective of this study was to establish the age at which mink kits develop
      functional homoeothermy. The investigation was based on the hypothesis that in
      this species with very immature neonates, late development of homoeothermy may be
      an adaptation to economize with energy. Measurements of heat production (HE) by
      means of indirect calorimetry lasting 3 h were performed on neonatal kits and
      kits from 1 to 54 days of age. Both single kits and groups of 4-5 huddling kits
      were kept at 15 degrees C (L) or 30 degrees C (H) [from 35 days onwards at 25
      degrees C (H)]. Animals were weighed before and after the experiments and
      evaporative water losses (EWL) were calculated. When exposed to L temperature,
      single kits responded with a very low HE until 29 days of age, and groups of kits
      until 14 days of age. It was not until they reached an age of approximately 6
      weeks that single kits showed a clear thermoregulatory response to the L
      temperature by increased HE, whereas groups of kits showed increased HE from 29th
      day onwards. When kept at H temperature, HE was low initially, but all kits
      showed elevated HE at 8 days of age, and the metabolic rate was similar for
      single kits and kits huddling in groups. Evaporative water losses was higher
      among single than among groups of kits and slightly lower but more variable for
      animals at L than at H temperature. It was concluded that mink kits develop
      functional homoeothermy at an age of close to 6 weeks and that the failure of
      very young kits to thermoregulate is an adaptation mechanism in order to
      economise with their very limited body energy reserves.

PMID- 16422769
TI  - Immersion booster vaccination effect on sea bass (Dicentrarchus labrax L.)
      juveniles.
AB  - In each challenge 30 sea bass juveniles (mean weight 3.3 +/- 0.2 g SD) were used.
      During the whole experiment (water T: 18 +/- 1 degrees C) the fish were held in
      four 50l seawater independent recirculation systems (one fish group per 50l
      system). The protection to the pathogen Vibrio anguillarum was tested on booster
      vaccinated sea bass (Dicentrarchus labrax L.) juveniles. The vaccination was
      performed by immersion for 60 s in a commercial anti-V. anguillarum vaccine
      suspension. Booster vaccination took place 60 days after the initial
      immunization. Thirty days after the booster vaccination all the fish received
      intraperitoneally (IP) 3.0 x 10(6) cfu/fish (colony forming units) virulent V.
      anguillarum bacteria. The booster vaccination showed a strong protection effect
      on the challenged sea bass. In the next 20 days after the challenge the mortality
      was 0% among the booster vaccinated sea bass, 10% among the once vaccinated fish
      and 50% in the control group (unvaccinated fish). No mortality was observed among
      the unvaccinated sea bass injected IP with sterile normal saline by the
      challenge.

PMID- 16422770
TI  - Assessment of dietary zinc requirement of weaned piglets fed diets with or
      without microbial phytase.
AB  - Fifty-four pigs, weaned at 26 days of age at an average body weight of 7.74 kg
      were used in a 26-day experiment to assess the zinc requirement of piglets, using
      diets based on maize and soybean meal, with or without microbial phytase. The
      nine experimental diets were the basal diet containing 33 mg of zinc/kg
      supplemented with 10, 25, 40, 60 or 80 mg of zinc as sulphate (ZnSO(4),
      7H(2)O)/kg and the basal diet supplemented with 0, 10, 25 or 40 mg of zinc as
      sulphate/kg and 700 units (U) of microbial phytase (Natuphos)/kg. Pigs were fed
      the basal diet for a 7-day adjustment period prior to the 19-day experimental
      period. Microbial phytase enhanced plasma alkaline phosphatase (AP) activity,
      plasma zinc and bone zinc concentrations. These parameters increased linearly
      with zinc intake, with a similar slope with and without phytase. The response of
      bone zinc-to-zinc added did not plateau. Without microbial phytase, plasma AP
      activity and zinc concentration were maximized when dietary zinc reached 86 and
      92 mg/kg respectively. With microbial phytase they were maximized when dietary
      zinc concentration reached 54 and 49 mg/kg respectively. Accounting for a safety
      margin, the recommended supply of zinc for weaned piglets up to 16 kg fed maize
      soybean meal diets supplemented with zinc as sulphate is thus of 100-110 mg/kg
      diet. This supply may be reduced by around 35 mg if the diet is supplemented with
      700 U of microbial phytase.

PMID- 16422772
TI  - Dietary lutein and fat interact to modify macrophage properties in chicks hatched
      from carotenoid deplete or replete eggs.
AB  - Two experiments were conducted to study the interaction between dietary lutein
      and fat levels in broiler chicks hatched from lutein depleted (Experiment I) and
      repleted (Experiment II) eggs. In both experiments, a 2 x 3 factorial arrangement
      of treatments resulted in six dietary treatments (fat at 3% and 6% and lutein at
      0, 25 and 50 mg/kg feed) that were fed for 23 days to 18 birds per treatment (in
      three replications). In Experiment I, the anti-dinitrophenyl-keyhole-lympet
      hemocyanin (anti-DNP-KLM) serum antibody response at day 22 and macrophage
      phagocytotic index at day 17 did not differ among treatment groups (p > 0.05).
      The concavalin A and phytohaemagglutinin-P lymphocyte proliferation index at day
      19 was greater in birds fed 50 mg of lutein and 3% fat than in birds fed all
      other diets (p < 0.05). Independent of the level of dietary fat, dietary lutein
      increased macrophage (day 23) nitrite production measured 46 h after in vitro
      stimulation with LPS (p < 0.05). Among the birds fed lutein at 25 or 50 mg/kg
      feed, birds fed 3% fat had higher LPS-induced nitrite production compared to the
      birds fed 6% fat after 46 (p = 0.014) or 70 h (p < 0.001). In Experiment II,
      macrophage nitrite production was measured at 54 h after LPS stimulation on days
      11, 15, 19 and 23. An interaction between dietary lutein and fat levels on
      nitrite production was observed on day 19 (p = 0.012), where macrophages from
      birds fed 0 mg lutein and 3% fat had the highest nitrite production (p = 0.012).
      Macrophages from birds fed lutein at 25 and 50 mg/kg diet and 3% fat had higher
      (p = 0.012) nitrite production than birds fed 6% fat. Thus, in birds hatched from
      lutein deplete and replete eggs, modulation of macrophage nitrite production by
      lutein is dependent on the level of dietary fat.

PMID- 16422771
TI  - A first estimate of the amino acid requirement for milk production of the high
      producing female mink (Mustela vison).
AB  - Thirty mink dams nursing litters of six kits were assigned to one of three
      dietary treatments [high protein (HP), medium protein (MP) and low protein (LP)],
      fed ad libitum for 4 week from parturition, to investigate the effects of protein
      supply on milk yield and milk composition in order to estimate the amino acid
      requirement of the lactating mink. Twelve dams were held in an intensive care
      unit and subjected to balance experiments and the kits were injected with
      deuterium oxide to determine water kinetics and milk yield. Eighteen dams were
      kept under normal farm conditions but with feed intake of dams and live weight
      gain of kits being determined and milk samples collected. The ME intake was
      higher (p < 0.05) in dams fed the LP and MP diets than in dams fed the HP diet,
      whereas the amino acid intake (g/day) was lowest (p < 0.05) in dams fed the LP
      diet. In the third and fourth weeks of lactation milk yield was higher (p < 0.05)
      in dams fed the LP and MP diets than in dams fed the HP diet. Chemical
      composition of milk was not affected (p > 0.05) by dietary treatment. However,
      protein content tended (p = 0.06) to be lower in dams fed the LP diet. Amino acid
      content (g/16 g N) of milk was higher (p < 0.05) in dams fed the LP and MP diets
      than in dams fed the HP diet. This resulted in the highest (p < 0.05) amino acid
      intake and highest (p < 0.001) live weights of kits nursed by dams fed the LP and
      MP diets, which may be explained by a combined effect of higher ME intake and
      reduced energetic costs for glucose production through less amino acids being
      used in gluconeogenesis. In conclusion, the improved performance of dams fed the
      LP diet suggested that their requirement of essential amino acids and non
      specific N were covered, and the requirement of digestible amino acids of
      lactating mink (kg(0.75)) was, thereby, estimated by use of a factorial approach
      including the amino acid excretion in milk of LP dams.

PMID- 16422773
TI  - Long-term effects of early-life dietary L-carnitine on lymphoid organs and immune
      responses in Leghorn-type chickens.
AB  - The long-term effects of supplementing Leghorn-type chickens with dietary L
      carnitine after hatching for 4 weeks on growth, lymphoid organ weights, humoral
      and cell-mediated immune responses were assessed in a 12-week study. A commercial
      starter feed supplemented with 0 (control), 100 (LC) or 1,000 (HC) mg L
      carnitine/kg was offered to day-old ISA Brown cockerels for 4 weeks, then all
      birds were given a commercial pullet grower feed for another 8 weeks. No
      differences (p > 0.05) in growth rates, feed intake or feed utilisation
      efficiency existed among the dietary treatments throughout the study. Compared
      with control birds, HC-fed birds had a lower (p < 0.05) thymus weight relative to
      bodyweight (BW) at Week 4, but a higher (p < 0.05) relative thymus weight at Week
      12. A higher (p < 0.05) serum primary antibody response to sheep red blood cells
      (SRBC) in HC-fed birds than in the other two groups was also detected at Week 12.
      Relative spleen or bursa weights and cutaneous responses of toe webs to
      phytohaemagglutimin (PHA) (an in vivo indicator of cell-mediated immune
      responses) did not differ (p > 0.05) among dietary treatments at any time. It is
      concluded that a short-term supply of dietary L-carnitine to a conventional
      commercial feed after hatching enhanced subsequent humoral immunity in Leghorn
      type chickens. Further study is warranted to confirm such a long-term effect.

PMID- 16422774
TI  - The objective assessment of international collaboration between pathology
      laboratories.
AB  - Collaboration between clinical laboratories in different countries is widespread
      but rarely subject to critical analysis. We developed a management tool for
      assessing the quality of an international pathology laboratory collaboration. Key
      areas of activity were identified and relevant performance indicators were
      established. There was no evidence of improved staff morale arising from the
      project but research, education, equipment, protocols and ethics activities all
      had demonstrable outputs. Identification of suboptimal performance in areas of
      the project allowed effective improvement planning. International collaboration
      may consume significant resources. Objective assessment should be used to measure
      performance and to enhance quality.

PMID- 16422775
TI  - Attributed disability: a spot of local difficulty.
AB  - There has been an exponential growth of publications relating to the development
      and application of health measurement instruments. Condition-specific measures
      have formed a large part of this trend. This article questions the rationale
      behind the concept of condition-specific disability, a common domain in such
      measures, taking musculoskeletal medicine as an example. It argues that physical
      functions are seldom unique to a specific condition and that measurement
      specificity therefore relies on attributing functional consequences to the health
      condition of interest. The presence of multi-morbidity (musculoskeletal and non
      musculoskeletal), and the influence of personal and environmental factors, pose
      problems for attribution that have seldom been empirically investigated.
      Furthermore, attributing disability to a specific health condition of interest
      potentially limits insights into important interventions such as managing co
      morbid interactions and targeting barriers in the physical, social, and
      attitudinal environment. Efforts to identify regionally relevant item content and
      to measure participation in daily life are a step in the right direction.
      Attribution is not needed for either.

PMID- 16422776
TI  - A systematic review on communicating with patients about evidence.
AB  - OBJECTIVE: To conduct a systematic search for (1) the effectiveness of evidence
      based communication tools to increase patient understanding of evidence, (2)
      effective formats for representing probabilistic information and (3) effective
      strategies for eliciting patient preferences about evidence. A case scenario is
      used to illustrate some of the difficulties of putting these results into
      practice. DATA SOURCES: Systematic search of The Cochrane Library, Medline,
      Psychinfo, Embase and Cancerlit. REVIEW METHODS: Systematic reviews of randomized
      controlled trials (RCTs) and high quality RCTs were included. Studies were
      excluded if they did not address the question, were focused on behavioural
      outcomes without attempting to increase understanding, were concerned with
      counselling as a therapeutic intervention, or were specific to communication
      regarding clinical trial participation. RESULTS: We found 10 systematic reviews
      of RCTs and 30 additional RCTs addressing our questions. Communication tools in
      most formats (verbal, written, video, provider-delivered, computer-based) will
      increase patients' understanding but are more likely to do so if structured,
      tailored and/or interactive. Probabilistic information is best represented as
      event rates (natural frequencies) in relevant groups of people, rather than
      words, probabilities or summarized as effect measures such as relative risk
      reduction. Illustrations such as cartoons, or graphs (vertical bar charts) appear
      to aid understanding. Values clarification exercises may be better than standard
      utility techniques for eliciting preferences in individual decision making.
      Looking for effective evidence-based communication tools for prostatic specific
      antigen testing highlighted the challenges for clinicians and consumers in
      accessing tools that are evidence-based in design as well as content. CONCLUSION:
      There is an increasing body of evidence supporting the design of effective
      evidence-based communication tools but variable access to such tools in practice.

PMID- 16422777
TI  - Diagnosis: contemporary medical hubris; Rx: a tincture of humility.
AB  - Despite increasing attention to evidence-based medicine, unprecedented advances
      in medical technology, and rapid diffusion of innovative information, there
      continues to be disturbing disclosures of widespread iatrogenic illness resulting
      from harmful medical interventions. The medical community at times displays a
      lethargic and lackluster response to important scientific and epidemiological
      data that challenges prevailing conventional wisdom or that elucidates existing
      medical miscalculations. To ensure that long-term health and well-being for
      patients and the community remains the primary goal of medicine, it is necessary
      to revisit the important issues of scientific integrity, health care objectives,
      and medical professionalism. Furthermore, to be trustworthy advisors for
      individual patients and credible advocates for the health of populations, the
      medical community needs to critically evaluate the profound influence of
      commercial interests on medical research, medical education and clinical
      practice.

PMID- 16422778
TI  - Oxygen therapy in hospitalized patients: the impact of local guidelines.
AB  - OBJECTIVE: To study the influence of local guidelines on the behaviour of nursing
      and medical staff to optimize the oxygen use in patients admitted to hospital.
      METHODS: Study was performed in a district teaching hospital. Guidelines produced
      suggested indications, monitoring, use of arterial blood gases (ABGs) and advice
      on when to stop oxygen therapy. The guidelines were implemented both verbally and
      in writing to all the nursing and medical staff before and after an audit
      studying the oxygen use by patients on medical and surgical wards. RESULTS:
      Ninety patients were included in pre-intervention audit and 59 in post
      intervention study. Oxygen prescription did not change with guidelines 30%
      (27/90) vs. 32% (19/59). Nurses administered oxygen better 95% (18/19) vs. 70%
      (19/27) (P = 0.043) and monitored more frequently using oximetry 91% (54/59) vs.
      69% (62/90) (P = 0.001) after the guidelines. Patients with airway disease had
      their ABGs checked more frequently 87% (14/16) vs. 65% (15/23) on admission and
      after they started oxygen inhalation 68% (11/16) vs. 34% (8/23). CONCLUSION: The
      guidelines disseminated verbally and in writing had no influence on oxygen
      prescription but improved the practice of close monitoring of patients with
      airway disease. Nurses improved their performance of both administration of
      oxygen according to the prescribed dose and monitoring with oximetry.

PMID- 16422779
TI  - Publishing outcome data: is it an effective approach?
AB  - RATIONALE, AIMS AND OBJECTIVES: The publication of health outcome data--rather
      than merely the measurement and collection--is being given increasing
      consideration. Publication reflects society's increasing emphasis on a general
      'right to know', as well as being a means of informing consumer choice. In
      theory, publication may help to promote public trust, support patient choice, and
      stimulate action to improve the quality of care whilst controlling costs.
      METHODS: Drawing on a literature review, this paper overviews the strategies
      employed in the UK and US to publish outcome data. The focus is on outcomes, and
      certain related process measures, that measure the performance of hospitals or
      surgeons. RESULTS AND CONCLUSIONS: Presenting the limited evidence that exists,
      we review the potential beneficial and harmful effects of publishing hospital
      outcome data. We also consider the risks of making incorrect inferences based on
      these data and the potential for dysfunctional consequences. Recognizing that the
      public largely mistrusts currently published health outcome data, we offer some
      recommendations for the future direction of strategies for publication.

PMID- 16422780
TI  - Exploring the continuum: medical information to effective clinical practice.
      Paper I: the translation of knowledge into clinical practice.
AB  - This paper investigates the translation of medical information into clinical
      practice and the role of thoughtful dissent by exploring the influence of
      sociological factors on change, the impact of evidence-based medicine (EBM), and
      the role of industry. Changing practice related to hormone therapy for menopausal
      and post-menopausal women provides context for this discussion. Medical change
      involves diffusion of ideas to potential users and ongoing reconciliation of new
      information with old ideas; this process is influenced by sociological factors
      including values and experiences, interpersonal relationships and local context.
      While EBM has alerted doctors to the importance of high quality research and
      theoretically provides a tool for translating research into practice, there are
      important problems with its application: (1) it has resulted in a reductionist
      approach to research and illness; (2) there is a considerable gap between
      research findings and the complex environment of clinical practice; and (3) EBM
      has been appropriated by experts, thus corporately developed 'standard-of-care'
      documents have become instruments of external regulation, and EBM has ceased to
      be a tool in the hand of individual clinicians. In addition, industry impacts the
      translation of knowledge by significantly influencing academia, researchers,
      medical publications, consensus conferences, and practising doctors. While
      questioning doctrinaire practices or directives is a daunting prospect for
      individual clinicians, the translation of knowledge into practice and evolution
      of medical thought is dependent on the progressive role of thoughtful dissent.

PMID- 16422781
TI  - Exploring the continuum: medical information to effective clinical practice.
      Paper II. Towards aetiology-centred clinical practice.
AB  - Contemporary clinical practice increasingly functions within a disease management
      paradigm aimed at finding and implementing therapeutic interventions that
      demonstrate efficacy in clinical trials. Disease prevention, elucidation of
      illness aetiology and proactive health promotion have taken a back seat. Current
      clinical care often includes a 'fast-food' type of medical encounter, which
      frequently neglects disease causality. The medical community is presently
      challenged by unique administrative and professional adversities as well as undue
      commercial influence; these factors contribute to a lethargic response to
      escalating rates of chronic illness and to mainstream medicine's relative
      inattention to emerging research about disease aetiology. Individual medical
      practitioners and the medical establishment must strategically seek to advance
      patient health and maintain professional relevancy by a renewed emphasis on the
      following principles: patient-based clinical care, aetiology-centred medicine,
      and proactive health promotion.

PMID- 16422782
TI  - A comparison of multivariable regression models to analyse cost data.
AB  - RATIONALE, AIMS AND OBJECTIVES: Analysis of cost data is important in providing
      reliable information to aid budgeting decisions. Certain features of cost data,
      such as its typically highly skewed distribution and the need to estimate
      arithmetic mean costs in order to allow inferences to be made on total costs,
      make it difficult to analyse. Multivariable regression analysis is useful for
      estimating the influence of explanatory variables on cost in order to predict
      costs of future patients and allows for the control of variables which influence
      cost but whose distributions differ between comparison groups. This is especially
      important in the case of observational studies, where there may be no control
      over the balance of characteristics between the comparison groups. METHOD: This
      paper compares the appropriateness of various multivariable models of cost data
      by examining regression diagnostics, using as an example data collected on costs
      incurred in the treatment of inflammatory bowel disease. The models compared are
      normal and bootstrapped multiple linear regression, median regression, gamma
      model with the log link and normal linear regression (NLR) of log costs. RESULTS:
      Gamma modelling with the log link was found to be the most suitable model.
      CONCLUSIONS: Bootstrapping was found to make very little difference to
      conclusions from the NLR model.

PMID- 16422783
TI  - Do case-generic measures of queue performance for bypass surgery accurately
      reflect the waiting-list experiences of those most urgent?
AB  - BACKGROUND: Queue performance is typically assessed using generic measures, which
      capture the queue in aggregate. The objective of this study was to examine
      whether case-generic measures of queue performance appropriately reflected the
      waiting-list experiences of those patients with greatest disease severity.
      METHODS: We examined the queue for isolated coronary artery bypass grafting
      (CABG) in Ontario between April 1993 and March 2000 using data obtained from the
      Cardiac Care Network. Our primary measure of queue performance was the proportion
      of patients who received their bypass surgery within their recommended maximum
      waiting times (%RMWTs) in any given month. We compared case-generic measures of
      queue performance to case-specific measures of queue performance stratified by
      urgency level. RESULTS: The queue was largely comprised of elective cases ranging
      from 73% (1993) to 57%(1999). Urgent patients comprised the minority of the queue
      ranging from 14% (1993) to 20% (1999). Case-generic month-to-month variations in
      the percentage of cases completed within RMWTs (an aggregated waiting list
      measure encompassing the characteristics of all patients in the queue) closely
      resembled the experiences of elective patients (R2 = 0.81), but conversely, bore
      little relationship to the waiting-list experiences of those most urgent (R2 =
      0.15). INTERPRETATION: Case-generic measures of queue performance for bypass
      surgery in Ontario were not reflective of the waiting-list experiences of those
      most urgent. Our results reinforce the concept that urgency-specific waiting list
      monitoring systems are required to best evaluate and appropriately respond to
      fluctuations in queue performance.

PMID- 16422784
TI  - Lessons from developing and running a clinical database for colorectal cancer.
AB  - BACKGROUND: Recent policy developments in the UK require the routine monitoring
      of the performance of cancer services. Developing and using clinical databases is
      one approach to meet this objective, but to date their implementation has been
      challenging. OBJECTIVE: To describe the development of the Thames Cancer Registry
      clinical database for colorectal cancer, and to present the lessons learnt in the
      first five years since its establishment. METHODS: Planning of this clinical
      database began in 1998. Detailed variables for the data set were derived by
      analysis of national standards and guidelines. Structured pro formas were
      designed to abstract data from clinical notes. A pilot study over 12 months
      collected 400 cases from seven hospital trusts in one cancer network. Data
      collection over the wider North Thames area began in 1999. RESULTS: The number of
      new records entered each year into the database rose from 747 in 1999 to 1107 in
      2002. By 2004, it held a total of 8500. However, participation and completeness
      of data collection varied between trusts. Currently only 18 of 26 trusts in the
      area submit data and only 12 have done so every year. Overall completeness for
      key demographic and treatment variables has been between 80 and 100% but less so
      for more detailed diagnostic and treatment variables (40-60%). Barriers to
      implementation in trusts could be grouped as organizational, professional and
      data-related. Organizational barriers have included changes in the cancer
      networks, variability in trust commitment to different data sets and lack of
      personnel to enter data consistently. Professional barriers have included
      competing priorities and varying commitments within the multidisciplinary
      clinical teams. Data-related barriers include the wide range of database formats
      that are used in trusts, and a tendency for data to be collected at the end of
      the year rather than continuously. CONCLUSIONS: Creating and maintaining a
      clinical database is a time-consuming and complex undertaking. Completeness of
      ascertainment and quality are major issues of concern. Key lessons from this
      project have been that the commitment of clinicians and the ability of trusts to
      provide consistent support for data collection are crucial.

PMID- 16422786
TI  - Evaluation of a community mental health carepath for early psychosis.
AB  - PURPOSE: To implement a carepath for early psychosis across all community mental
      health centres through the Early Psychosis Intervention Programme in the Fraser
      South Area of British Columbia, Canada. METHODS: Prior to developing the
      carepath, chart reviews and interviews were performed to assess for adherence to
      published guidelines for early psychosis intervention. This assessment revealed
      the inadequacies of narrative recording and that core psychosocial interventions
      were inconsistently provided. The carepath developed included prompts for
      interventions and standardized assessments and ultimately replaced the charting
      system used in the mental health centres for early psychosis clients. RESULTS AND
      CONCLUSIONS: One-year evaluation revealed some improvements in clinical practice
      but also identified other areas that require further improvement. This project
      demonstrated that it is possible to successfully implement a carepath in
      community mental health and that doing so provides a standardized method for
      ongoing improvements in care.

PMID- 16422785
TI  - Impact of an educational intervention to promote condom use among the male
      partners of HIV positive women.
AB  - RATIONALE AIMS AND OBJECTIVES: Promoting the secondary prevention of HIV
      transmission is essential. METHOD: An intervention. aimed at increasing condom
      use by partners. was delivered to HIV positive women attending a Brazilian
      clinic. It included educational advice delivered by doctors. and unlimited access
      to free condoms. A pre-post design was used: 170 control group women were
      recruited. the intervention was implemented. and 170 intervention group women
      were then enrolled. All were interviewed at baseline. 30 and 60 days. RESULTS:
      After training. doctors were more likely to provide advice on condom use.
      Reported use increased by 8.8% points (a 14.2% increase) in the intervention
      group after 30 days. and by 5.7 points (9.5%) in the control group (P = 0.52).
      CONCLUSION: The reasons why the intervention failed to reach a significant effect
      are discussed. as are the possible Public Health impact of a 14.2% increase in
      condom use among HIV positive women.

PMID- 16422788
TI  - Postmenopausal female sexual dysfunction: at a crossroads.

PMID- 16422789
TI  - Confronting the challenges: epidemiological study of female sexual dysfunction
      and the menopause.
AB  - INTRODUCTION: Despite rapid current and anticipated growth in the number of women
      who will spend a substantial portion of their life span in the postmenopausal
      period, the nature, incidence, and prevalence of changes in sexual function
      during and after the menopausal transition remain poorly characterized. AIM:
      Challenges inherent in studying the menopausal transition and proposed additions
      and changes that have emerged from recent consensus conferences on female sexual
      dysfunction are reviewed. METHODS: Specific topics related to female sexual
      dysfunction were presented in a Postmenopausal FSD Roundtable in which
      multidisciplinary international experts participated. MAIN OUTCOME MEASURE:
      Expert opinion was based on a review of evidence-based medical literature,
      presentation, and internal discussion. RESULTS: Knowledge concerning sexual
      function in the menopause is limited, in part, due to the difficulty in designing
      and conducting studies that adequately address these changes over time, and which
      also permit the effects of menopause to be distinguished from more general
      changes associated with aging. Moreover, the study of female sexual function and
      dysfunction is in the midst of significant transition: a tentative definition of
      the stages of reproductive aging and menopause has recently been advanced, and a
      set of comprehensive changes to the diagnostic framework that defines female
      sexual dysfunction is under review. CONCLUSIONS: In spite of fast-moving changes
      in this field of study, it is possible to reach some tentative conclusions about
      how women's sexual function changes after menopause: postmenopausal women report
      a relatively high rate of sexual dysfunction (higher than men). There is a marked
      decline in sexual interest and frequency of sexual activity. This decline can be
      ameliorated by a number of psychosocial factors, although vaginal dryness and
      dyspareunia seem to be driven primarily by declining estradiol. The effects of
      menopause appear to be incremental and additional to those characteristic of
      aging.

PMID- 16422790
TI  - Biological and psychosocial pathophysiology of female sexual dysfunction during
      the menopausal transition.
AB  - INTRODUCTION: Although increasing age is a primary determinant of reduced sexual
      function in older women, hormonal changes may be significant contributors to
      female (and couples') sexual dysfunction. AIM: To analyze the most relevant
      biological, psychosexual, and/or contextual factors that influence changes in
      women's sexuality during and after menopause. METHODS: A Postmenopausal FSD
      Roundtable consisting of multidisciplinary international experts was convened to
      review specific issues related to postmenopausal women and sexual dysfunction.
      MAIN OUTCOME MEASURE: Expert opinion was based on a review of evidence-based
      medical literature, presentation, and internal discussion. RESULTS: Menopause is
      associated with physiological and psychological changes that influence sexuality:
      the primary biological change is a decrease in circulating estrogen levels.
      Estrogen deficiency initially accounts for irregular menstruation and diminished
      vaginal lubrication. Continual estrogen loss is associated with changes in the
      vascular, muscular, and urogenital systems, and also alterations in mood, sleep,
      and cognitive functioning, influencing sexual function both directly and
      indirectly. The age-dependent decline in testosterone and androgen function,
      starting in the early 20s, may precipitate or exacerbate aspects of female sexual
      dysfunction; these effects are most pronounced following bilateral ovariectomy
      and consequent loss of 50% or more total testosterone. The contribution of
      progestogens to sexual health and variability in the effects of specific
      progestogens are being increasingly appreciated. Comorbidities, influenced by
      loss of sexual hormones, between mood and desire disorders and urogenital and
      sexual pain disorders are common and remain frequently overlooked in clinical
      practice. Physical and psychosexual changes may contribute to lower self-esteem,
      and diminished sexual responsiveness and sexual desire. Nonhormonal factors that
      affect sexuality are health status and current medication use, changes in or
      dissatisfaction with partner, partner's health and/or sexual problems, and
      socioeconomic status. CONCLUSION: Determination of the best way to provide
      optimal management of sexual dysfunction associated with menopause requires
      additional controlled studies.

PMID- 16422791
TI  - Current perspectives on the clinical assessment and diagnosis of female sexual
      dysfunction and clinical studies of potential therapies: a statement of concern.
AB  - INTRODUCTION: The assessment and diagnosis of female sexual dysfunction (FSD) are
      in a state of transition because of evolving concepts of female sexuality and
      suggested changes to the FSD diagnostic framework. AIM: To review the problems
      with current FSD diagnosis. METHODS: Multidisciplinary experts from five
      countries were assembled to convene a "Postmenopausal FSD Roundtable on specific
      topics related to FSD." MAIN OUTCOME MEASURE: Expert opinion was based on a
      review of evidence-based medical literature, presentation, and internal
      discussion. RESULTS: Current FSD diagnosis is challenging because of poorly
      defined distinctions between normal and abnormal, a limited ability to integrate
      subjective and objective findings and an inability to incorporate contextual
      factors that play a significant role in sexual behavior. The availability of self
      administered questionnaires (SAQs) that assess various domains of female sexual
      function, as well as those developed specifically for postmenopausal women,
      suggests that a more structured approach to assessment and diagnosis may be
      possible. Several SAQs reflecting proposed changes to the FSD diagnostic
      framework by the American Foundation for Urologic Disease (AFUD), including the
      Sexual Function Questionnaire (SFQ) and the Female Sexual Distress Scale (FSDS),
      have been introduced and recently incorporated into a Structured Diagnostic
      Method (SDM). Recent regulatory decisions and events affecting the development of
      FSD interventions have highlighted the lack of consensus with regard to
      clinically meaningful FSD outcomes, as well as shortcomings in a U.S. Food and
      Drug Administration draft document that provides the primary guidance for
      conducting FSD clinical studies in the United States. CONCLUSIONS: Given the high
      cost and inherent risk of clinical studies, continued development efforts toward
      FSD therapies are unlikely to proceed in the absence of significant changes in
      regulatory guidance that reflect the current understanding of FSD and incorporate
      validated assessment tools.

PMID- 16422792
TI  - Practical aspects in the management of vaginal atrophy and sexual dysfunction in
      perimenopausal and postmenopausal women.
AB  - INTRODUCTION: The decline in circulating estrogen levels in peri- and
      postmenopause has a wide range of physiological effects, including atrophy of
      tissues in the urogenital tract. Vaginal atrophy is an important contributor to
      postmenopausal sexual dysfunction. AIM: To provide a framework for clinical
      evaluation and clinical management of sexual dysfunction secondary to vaginal
      atrophy. METHOD: Conduct a brief overview of literature on evaluation and
      treatment of vaginal atrophy, augmented with the authors' clinical observations
      and experience. RESULTS: Estrogen decline disrupts many physiological responses
      characteristic of sexual arousal, including smooth muscle relaxation,
      vasocongestion, and vaginal lubrication; genital tissues depend on continued
      estrogen and androgen stimulation for normal function. An upward shift in vaginal
      pH as the result of vaginal atrophy alters the normal vaginal flora. Reduced
      lubrication capability and reduced tissue elasticity, in addition to shortening
      and narrowing of the vaginal vault, can lead to painful and/or unpleasant
      intercourse. At the same time, diminished sensory response may reduce orgasmic
      intensity. Other contributors to peri- and postmenopausal sexual dysfunction
      include reduced androgen levels, aging of multiple body systems, and side-effects
      of medications. Workup of sexual health problems starts by taking a comprehensive
      sexual, medical, and psychosocial history, followed by complete physical
      examination and laboratory evaluation. Clinical management includes measures to
      preserve and enhance overall health, adjustment of medication regimes to reduce
      or avoid side-effects, and topical or systemic hormone supplementation with
      estrogens and/or androgens. CONCLUSIONS: No single therapeutic approach is
      appropriate for every woman with peri- or postmenopausal sexual dysfunction;
      instead, treatment should be based on a comprehensive evaluation and
      consideration of medical and psychosocial contributors to the individual's
      dysfunction. Further research is required to establish optimal regimens of
      hormonal and nonhormonal agents, including dosages/dosage forms and duration of
      treatment, for specific subtypes of sexual dysfunction.

PMID- 16422794
TI  - Premature ejaculation: past, present, and future perspectives.

PMID- 16422795
TI  - Prevalence of premature ejaculation: a global and regional perspective.
AB  - The effort to determine the global burden of premature ejaculation (PE) has been
      impeded by the lack of a clear and universally accepted definition of the
      condition. Current diagnostic criteria are variable and rely, to a large degree,
      on subjective measurements. Moreover, the absence of a clear consensus on what
      constitutes a normal ejaculatory latency has impeded research into the prevalence
      of PE, although evidence is gradually accruing that may make this definition
      easier. Perception of "normal" ejaculatory latency varies by country and can
      differ when assessed either by the patient or their partner. Despite these
      limitations, information from the Global Study of Sexual Attitudes and Behaviors
      and other sources suggests a global prevalence of PE of approximately 30% across
      all age groups. The etiology underpinning this prevalence remains to be
      clarified, but current evidence reflects a shift from psychogenic theories to
      more neurobiological bases. While elucidation of the etiology of PE will
      undoubtedly aid the development of more effective therapies, it is clear that,
      whatever the cause of the condition, it is associated with a significant burden
      on psychological and overall health.

PMID- 16422796
TI  - Diagnosis and treatment of premature ejaculation: the physician's perspective.
AB  - Premature ejaculation (PE) is a common condition associated with significant
      adverse effects on the sexual and overall quality of life of men with this
      condition. Behavioral therapies, such as the "squeeze" and "stop-start"
      techniques, and psychotherapy, have been the mainstay of PE management for many
      years. However, evidence of their short-term efficacy is limited while support
      for their long-term benefit is lacking. There are currently no medications
      licensed specifically for the treatment of PE. This paucity of pharmacological
      treatment may, in turn, contribute to the absence of systematic procedures for
      the identification, evaluation, and treatment of PE patients. Current "off-label"
      pharmacotherapeutic approaches include topical anesthetics, phosphodiesterase-5
      inhibitors, and serotonin reuptake inhibitors. Of these, the serotonin reuptake
      inhibitors show the greatest efficacy and an increasing body of evidence is
      illuminating their mode of action. Nevertheless, all current "off-label"
      pharmacotherapeutic approaches fall short of the ideal therapy for PE. In the
      absence of a cure, such a treatment should be tolerable, inconspicuously used,
      effective from first dose, rapid in onset of action, and available as a prn
      dosing regimen. It is anticipated that agents in development for the specific
      indication of PE will come closer to this ideal than existing pharmacotherapeutic
      approaches.

PMID- 16422797
TI  - The burden of premature ejaculation: the patient's perspective.
AB  - Premature ejaculation (PE) remains an underdetected and under-treated condition,
      despite the advances in available treatment options. Men with PE often feel
      stigmatized by the condition and embarrassment is a key barrier to discussing the
      problem with healthcare professionals. Men with PE perceive themselves as having
      little control over ejaculation and this lack of control is mirrored in
      diminished satisfaction with sexual intercourse. The burden of PE is both
      emotional and physical. Premature ejaculation is associated with low self-esteem,
      anxiety, and feelings of shame and inferiority. In some studies there is an
      association with depression. Premature ejaculation places a significant burden on
      the patient-partner relationship and there is evidence to suggest that there is a
      higher prevalence of female sexual dysfunction associated with PE. Patients with
      PE often view the condition as purely psychological or as a problem that will
      resolve with time and many are unaware that medical treatment could be of
      benefit. This endorses the particularly important role of healthcare
      professionals in recognizing the barriers to patient diagnosis and promoting the
      view that PE is not only a common but also a treatable medical condition.

PMID- 16422798
TI  - Abstracts from the 7th Congress of the European Society for Sexual Medicine,
      London, United Kingdom, December 5-8, 2004.

PMID- 16422800
TI  - Phosphodiesterase 5 inhibitors and nonarteritic anterior ischemic optic
      neuropathy (NAION): coincidence or causality?

PMID- 16422801
TI  - The physiological role of androgens in penile erection: regulation of corpus
      cavernosum structure and function.
AB  - It is generally accepted that androgens are critical for development, growth, and
      maintenance of penile erectile tissue. However, their role in erectile function,
      especially in humans, remains controversial. Clinical and preclinical studies
      have suggested that venoocclusion is modulated by the tone of the vascular smooth
      muscle of the resistance arteries and the cavernosal tissue and a balance between
      trabecular smooth muscle content and connective tissue matrix. In men with
      erectile dysfunction, venous leakage is thought to be a common condition among
      nonresponders to medical management and is attributed to penile smooth muscle
      atrophy. In the animal model, androgen deprivation produces penile tissue atrophy
      concomitant with alterations in dorsal nerve structure, endothelial morphology,
      reduction in trabecular smooth muscle content, and increased deposition of
      extracellular matrix. Further, androgen deprivation results in accumulation of
      fat-containing cells (adipocytes) in the subtunical region of the corpus
      cavernosum. Androgen deficiency diminishes protein expression and enzymatic
      activity of nitric oxide synthases (eNOS and nNOS) and phosphodiesterase type 5
      (PDE5). The androgen-dependent loss of erectile response is restored by androgen
      administration but not by administration of PDE5 inhibitors alone. These data
      suggest that androgens regulate trabecular smooth muscle growth and connective
      tissue protein synthesis in the corpus cavernosum. Further, androgens may
      stimulate differentiation of progenitor cells into smooth muscle cells and
      inhibit their differentiation into adipocytes. Thus, we conclude that androgens
      exert a direct effect on penile tissue to maintain erectile function and that
      androgen-deficiency produces a metabolic and structural imbalance in the corpus
      cavernosum, resulting in venous leakage and erectile dysfunction. .

PMID- 16422802
TI  - Testosterone and sleep-related erections: an overview*.
AB  - Sleep-related erections have been reported to occur from the intrauterine life to
      senescence. It has been speculated that the main function of nocturnal erections
      is to provide adequate engorgement of the corpora cavernosa, which then leads to
      increased tissue oxygenation. This is in turn to prevent cavernous fibrosis, the
      histopathological basis for corporeal venoocclusive dysfunction, which probably
      is the most common cause of organic erectile dysfunction. It has been suggested
      that sleep-related erections are triggered by the release of nitric oxide by the
      nitrergic nerve fibers within the cavernous nerves. Androgens regulate this
      mechanism as well as some other non-nitrergic processes within the corpora
      cavernosa and within the central nervous system. By contrast, the erectile
      response to tactile or visual erotic stimuli in wakefulness predominantly
      involves an androgen-independent system, although it may, at least to a certain
      degree, also be influenced by androgen-sensitive mechanisms. No doubt, androgens
      are key players in the physiology of nocturnal erections, and the availability of
      new, user-friendly testosterone preparations such as transdermal gel and
      intramuscularly administered testosterone undecanoate stimulates further
      investigations on this field. The prospect that the quality of sleep may also be
      improved by an androgen therapy administered to improve sleep-related erections
      in hypogonadal men needs further basic research and appropriate clinical studies.

PMID- 16422803
TI  - Testosterone therapy in erectile dysfunction and hypogonadism.
AB  - INTRODUCTION: Laboratory experiments indicate that the nitric oxide erectile
      pathway is testosterone-dependent. Castration induces erectile dysfunction (ED)
      and reduction in nitric oxide synthase and in phosphodiesterase type 5 (PDE5) in
      the erectile tissue. Furthermore, castration causes apoptosis adversely affecting
      smooth muscle content and penile hemodynamics leading to veno-occlusive
      dysfunction. Testosterone therapy reverses these structural, biochemical, and
      physiological changes. In humans, testosterone therapy improves erectile function
      in men with hypogonadism. However, the efficacy of testosterone monotherapy may
      not be adequate because of the multifactorial nature of the pathophysiology of
      ED. METHODS: Preliminary data from a number of studies have been reviewed.
      RESULTS: There are emerging evidence-based benefits to using the combination of
      testoterone and PDE5 inhibitors. A recently published multicenter, randomized,
      placebo-controlled study evaluated the safety and efficacy of testosterone gel 1%
      plus sildenafil vs. placebo gel plus sildenafil, in producing an erectile
      response in hypogonadal men who had failed prior sildenafil alone for ED.
      Screening yielded a prevalence of hypogonadism in ED patients who failed prior
      sildenafil. Following randomization, the double-blinded treatment phase was 12
      weeks. Testosterone therapy with testosterone gel significantly improved erectile
      function in response to sildenafil. In addition, it significantly improved
      orgasmic function and patient satisfaction. CONCLUSION: It is important to screen
      all men with ED for hypogonadism, especially those with a history of inadequate
      response to prior PDE5 inhibitors. The combination of testosterone plus PDE5
      inhibitors may be considered for the treatment of ED in men with low to low
      normal testosterone levels, who had inadequate response to prior treatment with
      PDE5 inhibitors alone.

PMID- 16422804
TI  - Psychological and interpersonal dimensions of sexual function and dysfunction.
AB  - INTRODUCTION: There are limited outcome data on the efficacy of psychological
      interventions for male and female sexual dysfunction and the role of innovative
      combined treatment paradigms. AIM: To highlight the salient psychological and
      interpersonal issues contributing to sexual health and dysfunction; to offer a
      four-tiered paradigm for understanding the evolution and maintenance of sexual
      symptoms; and to offer recommendations for clinical management and research.
      METHODS: An International Consultation assembled over 200 multidisciplinary
      experts from 60 countries into 17 committees. The recommendations of committee
      members represent state-of-the-art knowledge and opinions of experts from five
      continents were developed in a process over a 2-year period. Concerning the
      Psychological and Interpersonal Committee of Sexual Function and Dysfunction,
      there were nine experts from five countries. MAIN OUTCOME MEASURE: Expert opinion
      was based on grading of evidence-based medical literature, widespread internal
      committee discussion, public presentation, and debate. RESULTS: Medical and
      psychological therapies for sexual dysfunctions should address the intricate
      biopsychosocial influences of the patient, the partner, and the couple. The
      biopsychosocial model provides a compelling reason for skepticism that any single
      intervention (i.e., a phosphodiesterase type 5 inhibitor, supraphysiological
      doses of a hormone, processing of childhood victimization, marital therapy,
      pharmacotherapy of depression, etc.) will be sufficient for most patients or
      couples experiencing sexual dysfunction. CONCLUSIONS: There is need for
      collaboration between healthcare practitioners from different disciplines in
      evaluation, treatment, and education issues surrounding sexual dysfunction. In
      many cases, neither psychotherapy alone nor medical intervention alone is
      sufficient for the lasting resolution of sexual problems. Assessment of male,
      female, and couples' sexual dysfunction should ideally include inquiry about:
      predisposing, precipitating, maintaining, and contextual factors. Treatment of
      lifelong and/or chronic dysfunction will be different from acquired or recent
      dysfunction. Research is needed to identify efficacious combined and/or
      integrated treatments for sexual dysfunction.

PMID- 16422805
TI  - The Sexual Interest and Desire Inventory-Female (SIDI-F): item response analyses
      of data from women diagnosed with hypoactive sexual desire disorder.
AB  - INTRODUCTION: Hypoactive sexual desire disorder (HSDD) is the most common sexual
      complaint in women. Currently there are no validated instruments for specifically
      assessing HSDD severity, or change in HSDD severity in response to treatment, in
      premenopausal women. The Sexual Interest and Desire Inventory-Female (SIDI-F) is
      a clinician-administered instrument that was developed to measure severity and
      change in response to treatment of HSDD. Seventeen items were included in a
      preliminary version of the SIDI-F, including 10 items related to desire, and
      seven items related to possible comorbid factors (e.g., other kinds of sexual
      dysfunction, general relationship satisfaction, mood, and fatigue). AIM: The aim
      of the study was to use the outcome of item response analyses of blinded data
      from two randomized, placebo-controlled trials, to assist in the revision of the
      scale. METHODS: A nonparametric item response (IRT) model was used to assess the
      relation between item functioning and HSDD severity on this preliminary version
      of the SIDI-F. RESULTS: Results show that the majority of SIDI-F items
      demonstrated good sensitivity to differences in overall HSDD severity. That is,
      there was an orderly relation between differences in option selection for an item
      and differences in overall HSDD severity. The IRT analyses further indicated that
      revisions were warranted for a number of these items. Five items were not
      sensitive to differences in HSDD severity and were removed from the scale.
      CONCLUSION: The SIDI-F is a brief, clinician-administered rating scale designed
      to assess severity of HSDD symptoms in women. IRT analyses show that majority of
      the items of the SIDI-F function well in discriminating individual differences in
      HSDD severity. A revised 13-item version of the SIDI-F is currently undergoing
      further validation.

PMID- 16422806
TI  - Women's sexual function improves when partners are administered vardenafil for
      erectile dysfunction: a prospective, randomized, double-blind, placebo-controlled
      trial.
AB  - INTRODUCTION: There are limited data concerning the sexual function of women
      whose male partners receive pharmacological treatment for erectile dysfunction
      (ED). AIM: One objective of this research was to prospectively compare the
      efficacy of vardenafil vs. placebo administered to men with ED in improving men's
      and women partners' sexual function and satisfaction. Another goal was to assess
      the relationship of erectile function changes in men with ED receiving treatment
      with sexual function changes in women partners not directly receiving treatment.
      METHODS: A randomized, double-blind, placebo-controlled, multi-institutional
      comparison of vardenafil vs. placebo was performed in 229 couples (treated man
      with ED>6 months and untreated woman partner). Co-primary outcomes for which this
      research was statistically powered were Sexual Encounter Profile (SEP3) (treated
      man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman
      partner). MAIN OUTCOME MEASURES: Erectile function changes in men with ED
      receiving vardenafil vs. placebo were compared at last observation carried
      forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and
      Erection Quality Scale (EQS). Sexual function at LOCF in women partners was
      determined by mSLQQ-QOL and Female Sexual Function Index (FSFI). RESULTS:
      Compared with placebo at LOCF, vardenafil significantly increased least square
      (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and
      EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal,
      lubrication, orgasm and satisfaction FSFI domains in untreated women partners.
      Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS
      was correlated reliably with improvement in women partners' FSFI total and
      individual domain scores. CONCLUSIONS: Vardenafil is an effective ED treatment in
      men that also significantly improves sexual function/satisfaction in untreated
      women partners. Women partners' sexual function improvements relate significantly
      and consistently to treatment-related improvements in men's erectile function. ED
      management should emphasize both members of the couple.

PMID- 16422807
TI  - Sexual dysfunction in female partners of men who have undergone radical
      prostatectomy correlates with sexual dysfunction of the male partner.
AB  - INTRODUCTION: Preservation and restoration of erectile function after radical
      prostatectomy (RP) for prostate cancer has been extensively studied. However, the
      influence of RP on the sexual function of female partners is poorly understood.
      AIM: The purpose of this retrospective study is to assess sexuality in men who
      have undergone RP for prostate cancer and their female partners. METHODS: Men who
      underwent RP for localized prostate cancer at our institution from 1996 to 2000
      were identified and invited to participate in this study with their female
      partners. Both partners completed a demographic survey. Men completed the
      International Index of Erectile Function (IIEF) and female partners completed the
      Female Sexual Function Index (FSFI) and supplemental questions. MAIN OUTCOME
      MEASURES: Correlation between IIEF and FSFI domain scores was determined in
      matched couples using Pearson correlation coefficient. Kappa statistics and
      Spearman correlation coefficient were calculated for supplemental questions and
      IIEF domain scores. RESULTS: Of 1,134 men contacted by letter, 90 (8%) couples
      completed demographic surveys and both the IIEF/FSFI. Pearson correlation
      coefficients of IIEF and FSFI domain scores in matched couples demonstrated
      significant correlation (P<0.05) of all IIEF domains with all FSFI domains with
      the exception of male erectile function and overall sexual function with female
      sexual desire. There was moderate agreement between partner supplemental
      questions and IIEF domain scores. CONCLUSIONS: Response rate was very low. FSFI
      domain scores correlate with IIEF domain scores, indicating an interrelationship
      between male and female sexual dysfunction in these couples. Evaluation and
      treatment of sexual dysfunction after RP should involve both partners.

PMID- 16422808
TI  - Flexible-dose vardenafil in a community-based population of men affected by
      erectile dysfunction: a 12-week open-label, multicenter trial.
AB  - AIM: To evaluate the efficacy, safety, and tolerability of a flexible-dose
      regimen of vardenafil in a community-based population of men with erectile
      dysfunction (ED). METHODS: This was a 12-week, open-label, flexible-dose,
      multicenter study of unselected men with ED of diverse origins and severity.
      Unlike previous studies, prostatectomy-induced ED and previous unresponsiveness
      to sildenafil were not exclusion criteria. After 4 weeks of treatment with 10 mg
      of vardenafil, the dose could be continued or titrated to 5 mg or 20 mg,
      depending on efficacy and tolerability. After 8 weeks, another dose change was
      possible. Efficacy was assessed with International Index of Erectile Function
      erectile function (IIEF-EF) domain scores, diary questions of the Sexual
      Encounter Profile (SEP), and a global assessment question (GAQ) about erection
      improvement during the previous 4 weeks. RESULTS: Safety was evaluated in 497
      patients, and 480 were suitable for intention-to-treat analysis. After 12 weeks
      of treatment, the mean per patient rate of successful intercourse, defined by an
      affirmative response to SEP questions 1-3, was 72%, and was related to age and ED
      duration. The overall success rate increased from 66% at week 4 to 77% at week
      12. The mean IIEF-EF domain score of the whole population increased from 17.2
      (baseline) to 24.4 (endpoint). At week 12, the best scores were obtained by
      patients taking 5 mg and 10 mg. At week 12, GAQ scores showed improved erection
      in 97.4%, 94.8%, and 78.8% of patients in the 5 mg, 10 mg, and 20 mg group,
      respectively. Safety was excellent: no serious drug-related event was reported,
      and only 2.2% of patients discontinued treatment because of side-effects.
      CONCLUSIONS: Vardenafil was effective and well tolerated in this community-based
      ED population that is truly representative of the general ED population. Dose
      titration meets the patient's needs and optimizes clinical outcome.

PMID- 16422809
TI  - Medication utilization behavior in patients receiving phosphodiesterase type 5
      inhibitors for erectile dysfunction.
AB  - INTRODUCTION: A number of preference studies have been conducted with
      phosphodiesterase type 5 (PDE5) inhibitor medications demonstrating inconsistent
      findings. Additionally, limited information is available regarding real-world
      utilization patterns of PDE5 inhibitors. AIM: To evaluate treatment patterns
      using real-world data for patients initiating erectile dysfunction (ED) therapy
      with Viagra (sildenafil citrate), Levitra (vardenafil), or Cialis (tadalafil).
      METHODS: Patients with an initial prescription claim for sildenafil, vardenafil,
      or tadalafil were identified in NDCHealth's Intelligent Health Repository.
      Medication refills, medication switching, and dose titration were analyzed.
      Logistic regression on the odds of refilling initial PDE5 medications was
      conducted controlling for patient age, presence of common comorbidities, initial
      number of tablets, and copay. RESULTS: A higher percentage of patients receiving
      sildenafil (52%) refilled their ED medication during the study period than
      patients receiving vardenafil (30%) or tadalafil (29%) (P<0.001). A smaller
      percentage of patients in the sildenafil cohort (6.4%) switched medication than
      in the tadalafil (9.0%) or vardenafil (10.4%) cohorts (P<0.001); the difference
      between the tadalafil and vardenafil cohorts in switching medications was also
      significant (P<0.001). There were no statistically significant differences
      between cohorts in dose titration frequency, which was low in all three treatment
      cohorts. Using logistic regression, the odds of refilling initial PDE5 therapy
      was significantly lower for vardenafil (odds ratio [OR]: 0.39, 95% confidence
      interval [CI]: 0.38-0.40; P<0.0001) and tadalafil (OR: 0.38, 95% CI: 0.37-0.40;
      P<0.0001) compared with sildenafil. CONCLUSIONS: Patients who were initially
      prescribed sildenafil were significantly more likely to refill their medication
      and significantly less likely to switch medications during the study period
      compared with patients who were initially prescribed vardenafil or tadalafil.
      These findings may indicate greater treatment satisfaction in patients receiving
      sildenafil, although future prospective evaluation is required.

PMID- 16422810
TI  - Safety and efficacy of vardenafil, a selective phosphodiesterase 5 inhibitor, in
      patients with erectile dysfunction and arterial hypertension treated with
      multiple antihypertensives.
AB  - INTRODUCTION: Vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, was
      evaluated in a prospective trial in the primary care setting involving
      hypertensive men with ED who were receiving at least one antihypertensive
      medication. AIMS: To investigate the safety and efficacy of flexible-dose
      vardenafil therapy compared with placebo in PDE5 inhibitor-naive subjects with
      arterial hypertension and ED. METHODS: In this multicenter, randomized, double
      blind, placebo-controlled study, 354 patients received placebo or vardenafil (5
      20 mg) for 12 weeks. Primary efficacy measures were diary responses to the Sexual
      Encounter Profile (SEP) questions 2 (vaginal insertion) and 3 (maintenance of
      erection). Additional efficacy measures included positive responses to the Global
      Assessment Question (GAQ). RESULTS: Compared with placebo, vardenafil
      significantly improved mean SEP2 and SEP3 success rates over the 12-week study
      period (intention-to-treat [ITT] and last observation carried forward [LOCF])
      analysis). For LOCF, SEP2 and SEP3 were 83% for vardenafil vs. 58% for placebo
      and 67% for vardenafil vs. 35% for placebo, respectively (P<0.0001 vs. placebo).
      Improved erections (GAQ) were experienced by 80% of vardenafil-treated patients
      at study end, compared with 40% for placebo (P<0.0001, LOCF). The most commonly
      reported treatment-emerging adverse events were headache (3.1%) and flushing
      (1.6%), which were mild-to-moderate and transient in nature. Importantly, there
      were no significant changes in systolic and diastolic blood pressure or heart
      rate between the vardenafil and placebo groups. The average number of
      antihypertensives used per patient was 1.5 and 1.4 in the vardenafil and placebo
      groups, respectively. Both the incidence of adverse events and the ability to
      maintain an erection were unaffected by stratification into distinct subsets
      according to the class of antihypertensive medication being received. CONCLUSION:
      Vardenafil significantly improves EF in hypertensive men treated with concomitant
      antihypertensive medication, is well tolerated, and does not significantly affect
      blood pressure.

PMID- 16422811
TI  - Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with
      lifelong premature ejaculation without erectile dysfunction.
AB  - INTRODUCTION: Apart from the involvement of central serotonergic
      neurotransmission on lifelong premature ejaculation, interference of thyroid
      function has been speculated. AIM: To study thyroid function in a large group of
      men with lifelong premature ejaculation (LPE). METHODS: Lifelong premature
      ejaculation was defined as an intravaginal ejaculation latency time (IELT) of
      less than 1 minute. Any consecutive man with LPE and no erectile dysfunction
      assessed by medical history and the International Index of Erectile Function
      (IIEF-5) was eligible for the study. Apart from the assessment of thyroid
      stimulating hormone (TSH) also free thyroxin (f T4) was determined in case of a
      TSH of <0.3 mU/L or TSH of >4.0 mU/L (being the lower and upper limits of normal
      values, respectively). Blood samples were drawn throughout the day within office
      hours. MAIN OUTCOME MEASURES: Thyroid-stimulating hormone and f T4. RESULTS:
      Included were 620 men; age (mean+/-SD) was 39.9+/-9.4 years (range 19-65). TSH
      concentrations from morning, early and late afternoon samples did not differ. The
      geometrical mean TSH concentration was 0.85 mU/L (95% confidence intervals: 0.82
      0.90) with a coefficient of variation of 57.9%. Fourteen men had a TSH of <0.3
      mU/L (2.2%), while five men (0.8%) of >4.0 mU/L. All men with an abnormal TSH had
      a normal f T4 (between 10 and 20 pmol/L). No relationship was found between age
      and TSH concentrations. CONCLUSION: Thyroid-stimulating hormone distribution was
      analyzed in a cohort of Dutch men with lifelong premature ejaculation and no
      erectile dysfunction. According to statistical analysis, there appeared to be no
      interaction between this ejaculatory complaint and the prevalence of thyroidal
      dysfunction. However, further studies are needed to gain more insight into the
      role of thyroid dysfunction and regulation of ejaculation time.

PMID- 16422815
TI  - Research on bicycle saddles and sexual health comes of age.

PMID- 16422816
TI  - Bicycle riding and erectile dysfunction: an increase in interest (and concern).
AB  - INTRODUCTION: From 1999 to 2004, there had been 21 publications from multiple
      medical specialties (sexual medicine, urology, neurology, cardiology, biomedical
      engineering, sports medicine, emergency medicine, and officials from the National
      Institute for Safety and Occupational Health) investigating the relationship
      between bicycle riding and erectile dysfunction (ED). In the previous 18 years,
      there have been 14 such studies. AIM: The primary aim was to summarize
      accumulating data on the safety of bicycle riding based on medical evidence
      categorized by levels of evidence, including case reports, observational studies,
      case control studies, mechanistic studies, and population-based epidemiologic
      investigations. The secondary aim was to address the concerns of bicyclists and
      propose measures to minimize the risk of ED associated with bicycle riding.
      METHODS: An English-language medical literature review was made of publications
      in peer review journals from 1981 to 2004, including published abstract
      presentations at major medical meetings. MAIN OUTCOME MEASURE: Ranked published
      epidemiologic data on bicycle riding and ED. RESULTS: Bicycle riding more than 3
      hours per week was an independent relative risk (RR = 1.72) for moderate to
      severe ED. In case control studies, the prevalence of moderate to severe ED in
      bicyclists was 4.2% and 4% vs. age-matched runners 1.1% (P < or = 0.018) and
      swimmers 2% (P = 0.05), respectively. Therefore, bicycle riders should take
      precautionary measures to minimize the risk of ED associated with bicycle riding:
      change the bicycle saddle with a protruding nose to a noseless seat, change the
      posture to a more upright/reclining position, change the material of the saddle
      (GEL), and tilt the saddle/seat downwards. CONCLUSIONS: The mechanism is
      hypothetically related to the rider interaction with the bicycle saddle at the
      perineum-saddle interface. Straddling bicycle saddles with a nose extension is
      associated with suprasystolic perineal compression pressures, temporarily
      occluding penile perfusion and potentially inducing endothelial injury and
      vasculogenic ED.

PMID- 16422817
TI  - Development of a new geometric bicycle saddle for the maintenance of genital
      perineal vascular perfusion.
AB  - OBJECTIVE: To identify a bicycle saddle model for cyclists who cover long
      distances, to minimally reduce the compression on the structures of the pelvic
      floor, thereby protecting blood perfusion of the penis and avoiding possible
      consequences on penile erection. MATERIALS AND METHODS: A comparison between a
      new geometric development of a bicycle saddle model (SMP) and one of the more
      frequently used models by professional cyclists was made. The measurement of the
      partial pressure of penile transcutaneous oxygen (PtcO(2)) in 29 healthy
      voluntary cyclists was recorded to investigate the differences of compression
      from two different saddles on the vascular structures of the perineum. The
      PtcO(2) was recorded at 3 and 10 minutes in conditions of static sitting. Then,
      the values of PtcO(2) were recorded for 15 minutes while the cyclists were in a
      60-degree position and in stable hemodynamic conditions. RESULTS: A t-test was
      performed to measure the level of confidence. The clear superiority of the SMP
      saddle in preventing vascular compression of the perineal structures was
      demonstrated to be statistically significant. CONCLUSION: The experiment
      validated the effectiveness of the SMP saddle in limiting the compression on the
      pelvic floor. In addition, the SMP saddle introduces compatible seat dimensions
      that cyclists prefer to cover long distances.

PMID- 16422818
TI  - Only the nose knows: penile hemodynamic study of the perineum-saddle interface in
      men with erectile dysfunction utilizing bicycle saddles and seats with and
      without nose extensions.
AB  - PURPOSE: To investigate the differential impact of straddles (A(ns) and B(ns))
      and noseless two-cheek seats (A(ntcs) and B(ntcs)) on penile hemodynamics and
      perineal compressive forces in subjects who cycle in a stationary bicycle.
      MATERIALS AND METHODS: Subjects underwent cavernosal artery peak systolic
      velocity (CAPSV) measurements after intracavernosal injection of vasoactive
      agents while supine, sitting upright on an examination table, straddling a
      saddle, sitting on a seat, and again supine. Mean perineal compression pressures
      recorded while straddling the saddles were compared with those while sitting
      upright. RESULTS: No differences were found in right and left CAPSV values while
      supine, sitting upright on an examination table, sitting on a seat, and supine
      again. Right/left CAPSV (cm/second) values straddling A(ns) and saddle B(ns) (0.7
      +/- 2.9/1.5 +/- 6.2 and 0/0, respectively) were significantly lower than values
      obtained while sitting on A(ntcs) and B(ntcs) (25.6 +/- 13.4/23.8 +/- 12.0 and
      17.3 +/- 6.4/18.3 +/- 6.5, respectively) (P < 0.001). Mean perineal compression
      pressures (mm Hg) on A(ns) and saddle B(ns) (315.2 +/- 39 and 387.9 +/- 64.3,
      respectively) were significantly higher than values obtained while sitting
      upright on an examination table (47.6 +/- 5.2 and 46.0 +/- 8.1, respectively) (P
      < 0.001). CONCLUSIONS: We have identified an objective test to assess if an
      individual bicycle rider, sitting on a certain shape of bicycle saddle or seat
      generates sufficient compressive forces at the perineal-saddle interface to
      obstruct cavernosal arterial inflow. This study also demonstrated that straddling
      bicycle saddles with nose extensions is associated with perineum-saddle interface
      compressive pressures that exceed systolic perfusion pressures, significantly
      diminishing penile hemodynamics.

PMID- 16422819
TI  - T-type (alpha1G) low voltage-activated calcium channel interactions with nitric
      oxide-cyclic guanosine monophosphate pathway and regulation of calcium
      homeostasis in human cavernosal cells.
AB  - INTRODUCTION: Nitric oxide-cyclic guanosine monophosphate (NO-cGMP)-mediated
      relaxation of cavernosal smooth muscle during erection is accompanied by a
      decrease in intracellular calcium concentrations ([Ca2+](i)). However, it is not
      known whether and how an increase in [Ca2+](i) is responsible for (i) initiating
      smooth muscle contraction/detumescence following relaxation; and (ii) maintaining
      the penis in a flaccid state under nonstimulating conditions. AIM: To elucidate
      (i) the mechanism(s) of [Ca2+](i) homeostasis regulation in human cavernosal
      smooth muscle cells (HCSMC); and (ii) how NO-cGMP interacts with such [Ca2+](i)
      homeostasis. METHODS: We evaluated the expression and function of both T-type and
      L-type Ca2+ channels in HCSMC by employing selective probes/inhibitors using
      various cellular and molecular techniques (e.g., reverse transcriptase and real
      time polymerase chain reaction, cell proliferation assay, fura-2 Ca2+
      fluorescence spectroscopy, enzyme-linked immuno-absorbent assay (ELISA)). MAIN
      OUTCOME MEASURE: We have demonstrated for the first time significant interactions
      of NO-cGMP with the T-type (alpha1G) Ca2+ channel in HCSMC. RESULTS: Our results
      suggest that in addition to NO-induced rapid and transient decrease in [Ca2+](i)
      that results in smooth muscle relaxation, NO-cGMP also enhanced mRNA expression
      of the T-type (alpha1G) Ca2+ channel resulting in delayed elevation of [Ca2+](i).
      This could be abolished by a selective T-channel blocker, NNC 55-0396. Another
      unique finding of this study is that dose-dependent HCSMC proliferation in vitro
      by NO is associated with the activation of the T-type (alpha1G) Ca2+ channel that
      regulates [Ca2+](i) homeostasis in these cells. CONCLUSIONS: Human cavernosal
      cells express T-type (alpha1G) Ca2+ channels that are involved in maintaining
      [Ca2+](i) homeostasis and regulation of NO-cGMP-induced smooth muscle relaxation
      contraction responsible for penile erection, flaccidity, and tonicity. Targeting
      these Ca2+ channels may (i) associate various comorbidities with the onset of
      erectile dysfunction; (ii) provide a biochemical basis for differences between
      therapeutic profiles of various phosphodiesterase type 5 inhibitors, especially
      in nonresponders to current therapy; and (iii) provide biochemical basis in
      understanding mechanism(s) of drug tolerance.

PMID- 16422821
TI  - An evaluation of a telephone follow-up clinic in urology.
AB  - OBJECTIVE: To evaluate the introduction of telephone follow-up reviews for
      prescriptions of oral erectogenic agents. PATIENTS AND METHODS: 124 men of 166
      invited patients who had participated in telephone consultations during the first
      12 months of operation. RESULTS: 91.9% of respondents found the telephone clinic
      more convenient than traditional attendance particularly because the former
      requires no travel and waiting time to be seen by a consultant. CONCLUSION: Men
      with erectile dysfunction can be followed up by telephone in the majority of
      cases where an oral erectogenic agent has been prescribed.

PMID- 16422820
TI  - Cholesterol feeding reduces vascular endothelial growth factor signaling in
      rabbit corporal tissues.
AB  - PURPOSE: Hypercholesterolemia is a major risk factor for erectile dysfunction
      (ED), but the mechanisms are not completely understood. Vascular endothelial
      growth factor (VEGF) is reduced in rabbit corporal tissue with cholesterol
      feeding. VEGF signaling leads to the phosphorylation of Akt and endothelial
      nitric oxide synthase (p-Akt and p-eNOS). MATERIAL AND METHODS: New Zealand White
      rabbits (n = 50) were fed a 1% cholesterol (n = 8, 8, 8, 4) or normal (n = 6, 6,
      6, 4) diet for 2, 4.5, 7.5, and 12 weeks. Akt, p-Akt, and p-Akt/Akt were measured
      by enzyme-linked immunosorbent assay. Levels of eNOS, p-eNOS, and neuronal and
      inducible nitric oxide synthase (nNOS and iNOS) mRNA and protein were assessed by
      polymerase chain reaction and Western analysis. RESULTS: Cholesterol feeding was
      associated with a significant decrease in p-Akt/Akt 2.16-fold (P < 0.05), 3.28
      fold (P < 0.02), and 3.42-fold (P < 0.02) at 4.5, 7.5, and 12 weeks,
      respectively. The reduction in p-Akt/Akt with the cholesterol diet at 2 weeks was
      not significantly different, but the correlation between the duration of
      cholesterol feeding and the reduction in p-Akt/Akt was high (r( 2) = 0.858). eNOS
      protein or mRNA did not change with cholesterol feeding, but p-eNOS was
      significantly decreased at 4.5 weeks and all subsequent time points. nNOS mRNA
      and protein levels were decreased at 4.5 weeks and all subsequent time points,
      while iNOS was not different between groups. CONCLUSIONS: Hypercholesterolemia
      results in decreased VEGF signaling and decreased levels of the active form of
      eNOS in corporal tissue. Levels of nNOS were reduced by a different mechanism.
      VEGF signaling may provide a target to modulate ED.

PMID- 16422822
TI  - Assessment of cerebrocortical regions associated with sexual arousal in
      premenopausal and menopausal women by using BOLD-based functional MRI.
AB  - PURPOSE: The aim of this study was to compare the cerebral regions associated
      with sexual arousal between premenopausal and menopausal women by using
      functional magnetic resonance imaging (f MRI). MATERIALS AND METHODS: Ten
      premenopausal and 10 menopausal women underwent fMRI on a 1.5T MR scanner using
      the blood oxygen level dependent technique. To identify the activated brain
      regions associated with sexual response, brain activation was assessed during 1
      minute of a nonerotic film, followed by 4 minutes of an erotic film. RESULTS: The
      overall activation ratios of the premenopausal women were greater than those of
      the menopausal women by approximately 8% on average. The limbic, temporal
      association areas, and parietal lobe showed greater enhancement of signal
      intensities in premenopausal women. However, signal enhancement in the genu of
      the corpus callosum and superior frontal gyrus was dominant in menopausal women.
      CONCLUSIONS: The activated brain center associated with visually evoked sexual
      arousal showed qualitative and quantitative differences between premenopausal and
      menopausal women.

PMID- 16422823
TI  - Women's sexual concerns: data analysis from a help-line.
AB  - PURPOSE: To report female sexual problems and concerns, as presented by women
      calling a help-line, and to evaluate women's help-seeking behavior regarding
      sexual matters. MATERIALS AND METHODS: The study included all telephone calls
      from women who called for sexual concerns to a help-line dedicated to sexual
      problems during a 5-year period. During the call, the counselor addresses
      demographic characteristics of the caller, the sexual problem reported, their
      sexual function, any previous doctor contacts, coexisting physical and mental
      health problems, couple's relationship, and lifestyle factors that may influence
      sexual function. Data processing employed descriptive statistics and logistic
      regression analysis in order to detect possible associations between categorical
      variables. RESULTS: Of a total of 3,523 calls made by women, 2,287 full forms
      were analyzed, reflecting a response rate of 64.9%. Most women (46.6%) called for
      problems encountered by their partners, 45.1% called for their own sexual
      problems, while 5.9% were calling for their children. Only 34.3% of them had
      already consulted a doctor. The most frequently reported difficulties were
      achieving orgasm (25.6%), reduced sexual desire (16.9%), and pain during
      intercourse (6.1%). Women in the 40-49 age group had the higher odds ratios for
      the sexual problems reported (reduced sexual desire: odds ratio [OR] 5.0;
      difficulties achieving orgasm: OR 6.3; pain during intercourse: OR 5.8). Both
      married and single women had high risk of experiencing low levels of sexual
      desire (40% and 30%, respectively). CONCLUSIONS: Women's sexual concerns are not
      devoted to their sexual problems, but also their partner's and children's
      problems. Most frequently reported sexual problems are difficulties in reaching
      orgasm and reduced sexual desire. However, women are reluctant to seek medical
      advice on their sexual concerns. There is a need for general practitioners and
      family doctors to become aware of the possibility of a sexual problem and to be
      trained on how to manage this at a primary care level.

PMID- 16422824
TI  - Efficacy of sildenafil citrate in men with erectile dysfunction following radical
      prostatectomy: a systematic review of clinical data.
AB  - INTRODUCTION: Radical prostatectomy is a frequently used treatment option for
      prostate cancer; however, prostatectomy is often associated with significant
      morbidity, including erectile dysfunction (ED). AIM: To analyze the efficacy of
      sildenafil citrate in treating ED after radical prostatectomy. MATERIALS AND
      METHODS: MEDLINE and CANCERLIT (1998 to January 2004) were searched for English
      language articles using the key words prostatectomy, sildenafil, and
      phosphodiesterase inhibitors. Eleven studies fulfilled the inclusion criteria:
      primary, discrete data sets of postprostatectomy patients with ED treated with
      sildenafil monotherapy. RESULTS: Sample sizes ranged from 13 to 198 (mean age, 61
      +/- 3 years). Treatment durations were 4 weeks (or more than four doses) to 1
      year, and sildenafil dosing was in the recommended range (25-100 mg). Seven
      studies reported a response rate (range, 14%-53%) for an end point consistent
      with the primary analysis outcome (erection sufficient for vaginal intercourse);
      the combined estimate of probability of response was 35% (95% confidence interval
      [CI], 24%-48%). There was strong evidence for a lower response rate after non
      nerve-sparing (range, 0%-15%) versus nerve-sparing surgery (range, 35%-75%;
      combined odds ratio [OR] = 12.1; 95% CI, 5.5-26.6) but not after unilateral
      (range, 10%-80%) versus bilateral nerve-sparing surgery (range, 46%-72%; combined
      OR = 2.21; 95% CI, 0.75-6.54). CONCLUSIONS: The results of these studies
      demonstrate that with sildenafil, more than one third of patients with
      postprostatectomy ED achieved erection sufficient for intercourse. The odds of
      responding improved 12-fold with preservation of at least one neurovascular
      bundle. Early treatment failure does not necessarily imply lack of efficacy in
      the future, and patients should be encouraged to continue trying sildenafil,
      titrating up to 100 mg as needed.

PMID- 16422825
TI  - Sexual intercourse attempt patterns with two dosing regimens of tadalafil in men
      with erectile dysfunction: results from the SURE study in 14 European countries.
AB  - OBJECTIVE: To describe the pattern of sexual attempts by men with erectile
      dysfunction (ED) taking tadalafil 20 mg on demand or on an alternative dosing
      regimen, 3 times/week, and to assess changes in sexual behavior when the patients
      were exposed to the alternative regimen. DESIGN AND METHODS: Scheduled use versus
      on-demand regimen evaluation (SURE) is a multicenter, crossover, open-label study
      conducted in 14 European countries. Men with ED (N = 4,262) were randomized to
      tadalafil 20 mg on-demand treatment (maximum one dose per day and before sexual
      activity) or 3 times/week for 5-6 weeks. After a 1-week washout period, patients
      were crossed over to the alternative regimen for 5-6 weeks. RESULTS: Nearly half
      (47%) of the attempts on the on-demand regimen and 71% of the attempts on the 3
      times/week treatment were performed by patients more than 4 hours post dosing.
      Sexual activity occurred throughout the week on both regimens, with the highest
      percentage of attempts made during the weekend (50% on on-demand and 48% on 3
      times/week) and evening and morning hours. The efficacy of tadalafil was more
      than 70% mean-per-patient success rate (Sexual Encounter Profile question 3)
      regardless of the time interval post dosing. CONCLUSIONS: Patients on tadalafil
      changed their sexual behavior significantly when on an alternative dosing regimen
      (3 times/week) and had sexual attempts distributed over a wide period of time
      post dosing. A substantial number of sexual attempts were performed beyond the
      first 4 hours post dosing on both regimens (47% for on-demand and 71% for 3
      times/week) and preferably in the evening and morning hours. Tadalafil was
      efficacious regardless of the time interval post dosing-i.e., up to 36 hours. The
      two treatment regimens, on-demand and 3 times/week, provide an additional option
      and unique flexibility in dosing for men with ED and their partners.

PMID- 16422826
TI  - Sexual experience of female partners of men with erectile dysfunction: the female
      experience of men's attitudes to life events and sexuality (FEMALES) study.
AB  - INTRODUCTION: Much research has explored the experience of erectile dysfunction
      (ED) among men with ED, but far less attention has been paid to the perceptions
      and sexual experiences of the female partners of men with ED. AIM: The objective
      of this study was to characterize the attitudes, beliefs, and sexual experience
      of female partners of men with erectile difficulties. METHODS: Female partners of
      men with ED who had participated in the Men's Attitudes to Life Events and
      Sexuality (MALES) study were recruited for this research via mail or Internet,
      after their male partners consented to this contact. Female partners of men with
      ED (N = 293) responded to questionnaire measures assessing their frequency of
      sexual activity and the nature of their sexual experience, both before and after
      the development of their partner's ED, and in relation to their partner's use of
      phosphodiesterase type 5 (PDE5) inhibitors. RESULTS: Women reported engaging in
      sexual activity significantly less frequently after their partner developed ED in
      comparison with before (P < 0.001). Moreover, significantly fewer women
      experienced sexual desire, arousal, or orgasm "almost always" or "most times,"
      and significantly fewer women reported satisfaction with their sexual
      relationship after their partner developed ED, compared with before (P < 0.001).
      Decreases in female sexual satisfaction and frequency of orgasm were
      significantly related to the male partner's self-reported severity of ED (P <
      0.01). The proportion of women who experienced sexual desire, arousal, and orgasm
      "almost always" or "most times" was significantly higher in the group whose
      partners were currently using a PDE5 inhibitor (P < 0.05). CONCLUSION: Erectile
      dysfunction has significant adverse effects on the female partner's sexual
      experience. Women with partners who were currently using PDE5 inhibitors had a
      more satisfying sexual experience than those whose partners did not use a PDE5
      inhibitor.

PMID- 16422827
TI  - Efficacy and safety of oral tadalafil in the treatment of men in Canada with
      erectile dysfunction: a randomized, double-blind, parallel, placebo-controlled
      clinical trial.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent, often undertreated
      condition. AIM: This 12-week, double-blind, parallel, placebo-controlled study
      was conducted at 25 sites in Canada to evaluate the efficacy and safety of oral
      tadalafil, a phosphodiesterase type 5 inhibitor, for the treatment of ED.
      METHODS: Men with ED of organic, psychogenic, or mixed etiology were stratified
      by baseline ED severity then randomly assigned to placebo (N = 50), tadalafil 10
      mg (N = 103), or tadalafil 20 mg (N = 100), taken as needed (maximum, once
      daily). MAIN OUTCOME MEASURES: Efficacy was assessed by the International Index
      of Erectile Function (IIEF), a Sexual Encounter Profile diary, and a global
      assessment question (GAQ). RESULTS: Tadalafil 10 mg and tadalafil 20 mg
      significantly improved erectile function compared with placebo (P < 0.001, all
      measures). At end point, the mean IIEF erectile function (EF) domain scores were
      14.5, 21.2, and 23.3 of a possible score of 30 for placebo, tadalafil 10 mg, and
      tadalafil 20 mg, respectively. Patients treated with tadalafil reported greater
      change from baseline on the IIEF EF domain score compared with placebo,
      regardless of baseline ED severity. During treatment, the mean per-patient
      proportion of successful intercourse attempts was higher for tadalafil 10 mg and
      20 mg than for placebo (placebo, 31.9%; tadalafil 10 mg, 56.7%; and tadalafil 20
      mg, 61.5%), and a greater proportion of patients reported improved erections with
      tadalafil (GAQ; placebo, 22.0%; tadalafil 10 mg, 67.0%; tadalafil 20 mg, 79.0%).
      Fifty percent and 62% of patients treated with tadalafil 10 mg and 20 mg,
      respectively, achieved successful sexual intercourse after their first dose,
      compared with 31% with placebo. Treatment-emergent adverse events were generally
      mild or moderate. CONCLUSION: Tadalafil was an effective, well-tolerated therapy
      for ED of broad-spectrum etiology and severity.

PMID- 16422828
TI  - Improving the sexual quality of life of couples affected by erectile dysfunction:
      a double-blind, randomized, placebo-controlled trial of vardenafil.
AB  - INTRODUCTION: Erectile dysfunction (ED) has a dual negative impact on men and
      their female partners; both are likely to face a drop in sexual quality of life
      and challenges to their intimate relationship as couples' sexual activities are
      curtailed by the loss of erectile function. AIM: The primary objective of this
      study was to compare the efficacy of vardenafil vs. placebo in terms of success
      of maintenance of erection in men with ED and improvement of their female
      partner's sexual quality of life. METHODS: This was a randomized, double-blind,
      multicenter, flexible-dose, parallel-group comparison of vardenafil vs. placebo
      for 12 weeks in men (> or =18 years) with ED of > or = 6 months duration, and
      their female partners. MAIN OUTCOME MEASURES: Changes in patient's overall
      response rate to Sexual Encounter Profile question 3 (SEP3) "Did your erection
      last long enough for you to have sexual intercourse?" and female partner's
      response to the quality of life domain of the modified Sexual Life Quality
      Questionnaire (mSLQQ-QOL) at last observation carried forward (LOCF) were
      considered the primary efficacy measures. In addition, patient's response to SEP2
      "Were you able to insert your penis into your partner's vagina?," the erectile
      function domain of the International Index of Erectile Function (IIEF-EF) and
      patient's mSLQQ-QOL score were also assessed. RESULTS: Compared with placebo,
      vardenafil significantly improved overall least square (LS) mean per-patient SEP3
      success rate (28% vs. 68%; P < 0.0001) and partner's LS mean (standard error
      [SE]) mSLQQ-QOL score at LOCF (32.14 [3.24] vs. 65.80 [3.10]; P < 0.0001). In
      addition, compared with placebo, vardenafil also improved overall LS mean per
      patient SEP2 success rate (47% vs. 80%; P < 0.0001), LS mean (SE) IIEF-EF scores
      at LOCF (12.7 [0.8] vs. 22.8 [0.8]; P < 0.0001) and patient's LS mean (SE) mSLQQ
      QOL (28.37 [3.46] vs. 63.85 [3.28]; P < 0.0001) at LOCF. CONCLUSIONS: Vardenafil
      improved erectile function in men with ED and improved the sexual quality of life
      of the couple.

PMID- 16422829
TI  - The impact of intralesional interferon alpha-2b injection therapy on penile
      hemodynamics in men with Peyronie's disease.
AB  - INTRODUCTION: Penile duplex Doppler ultrasound (PDDU) is currently the preferred
      method for the functional evaluation of penile hemodynamics. PDDU may be used to
      monitor objectively changes in penile vascular parameters in men who undergo
      treatment for Peyronie's disease (PD), including intralesional interferon alpha
      2b (IFN alpha-2b). AIM: To investigate the impact of intralesional IFN alpha-2b
      therapy for PD on penile hemodynamics by using PDDU and to assess the objective
      role of PDDU in monitoring treatment outcomes. MATERIALS AND METHODS: Thirty-nine
      patients (20 in the placebo and 19 in the IFN alpha-2b treatment arm) were
      enrolled in this prospective, placebo-controlled, parallel study. Patients
      received either 10 mL saline or 5 x 10(6) units of IFN alpha-2b intralesional
      injections every other week for a total of six injections. Patients in each group
      were evaluated at baseline and after completion of treatment regarding changes in
      penile hemodynamic parameters, penile curvature, plaque size and density, pain on
      erection, and erectile function. Specific published criteria were used for PDDU
      measurements. Outcomes were statistically compared between each group by using
      Mann-Whitney U and chi-square tests. RESULTS: The mean age of the patients and
      the duration of PD were similar in both groups. The improvement in penile blood
      flow was significantly greater in IFN alpha-2b-treated patients than those in the
      placebo group. The number with the nonvascular classification increased
      significantly in the IFN alpha-2b arm from 31.5% to 57.8%. Additionally,
      improvements in penile curvature, plaque size and density, and pain on erection
      were better in the IFN alpha-2b group compared with the control. No significant
      improvement was observed in the erectile function domain in either group.
      CONCLUSION: This study reveals that intralesional IFN alpha-2b injections have a
      significant benefit on penile hemodynamic parameters. Moreover, intralesional IFN
      alpha-2b is an effective, minimally invasive treatment for PD, and PDDU is a
      useful adjunct to monitor objectively changes in penile vascular parameters.
      interferon alpha-2b injection therapy on penile hemodynamics in men with
      Peyronie's disease.

PMID- 16422830
TI  - Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism.
AB  - AIM: Symptomatic late-onset hypogonadism is associated not only with a decline in
      serum testosterone, but also with a rise in serum estradiol. These endocrine
      changes negatively affect libido, sexual function, mood, behavior, lean body
      mass, and bone density. Currently, the most common treatment is exogenous
      testosterone therapy. This treatment can be associated with skin irritation,
      gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts.
      In this study we investigated the efficacy of clomiphene citrate in the treatment
      of hypogonadism with the objectives of raising endogenous serum testosterone (T)
      and improving the testosterone/estrogen (T/E) ratio. METHODS: Our cohort
      consisted of 36 Caucasian men with hypogonadism defined as serum testosterone
      level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg
      clomiphene citrate and followed prospectively. Analysis of baseline and follow-up
      serum levels of testosterone and estradiol levels were performed. RESULTS: The
      mean age was 39 years, and the mean pretreatment testosterone and estrogen levels
      were 247.6 +/- 39.8 ng/dL and 32.3 +/- 10.9, respectively. By the first follow-up
      visit (4-6 weeks), the mean testosterone level rose to 610.0 +/- 178.6 ng/dL (P <
      0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 (P < 0.001). There
      were no side effects reported by the patients. CONCLUSIONS: Low dose clomiphene
      citrate is effective in elevating serum testosterone levels and improving the
      testosterone/estradiol ratio in men with hypogonadism. This therapy represents an
      alternative to testosterone therapy by stimulating the endogenous androgen
      production pathway.

PMID- 16422831
TI  - The antimasturbation crusade in antebellum American medicine.
AB  - The antimasturbation fervor that swept through the English-speaking world during
      the 19th century raged with particular intensity and unequaled duration in the
      United States. American medical leaders were convinced that masturbation was the
      underlying cause of nearly all social problems and diseases. Even after the
      discovery and general acceptance of the germ theory of disease in the late 19th
      century, the U.S. medical establishment continued to maintain well into the
      middle of the 20th century that masturbation was both a pathological act and a
      cause of mental and physical disease. This article explores the dominant themes
      in the medical doctrines about masturbation that prevailed in the first half of
      the 19th century, by examining the case reports of five prominent American
      physicians: Benjamin Rush, Samuel Bayard Woodward, Alfred Hitchcock, Alonzo
      Garwood, and Edward H. Dixon.

PMID- 16422832
TI  - Idiopathic stuttering priapism treated successfully with low-dose ethinyl
      estradiol: a single case report.
AB  - INTRODUCTION: Chronic priapism represents a challenging therapeutic dilemma.
      Inadequate or deferred treatment can result in impaired quality of life and
      permanent erectile dysfunction. The etiology of stuttering priapism is speculated
      to be initially an ischemic injury that damages the neurologic and/or endothelial
      mediated mechanisms that normally regulate detumescence and maintain penile
      flaccidity. AIM: We report a case of stuttering priapism successfully treated
      with low-dose ethinyl estradiol. METHODS: A 51-year-old man presented with
      idiopathic stuttering priapism. Treatment was given in the form of low-dose
      ethinyl estradiol for six consecutive weeks. RESULTS: Moderate lowering of
      testosterone level and effective prevention of priapism for at least 6 months
      with retaining of erectile function. CONCLUSION: The use of low-dose estrogen
      shows a potential to be an effective and relatively rapid treatment option for
      some cases of idiopathic stuttering priapism.

PMID- 16422833
TI  - Rare complication of multiple revision surgeries of penile prosthesis.
AB  - INTRODUCTION: Migration of the penile prosthesis reservoir into the bladder is
      rare. METHODS: A 67-year-old male was found with painful gross hematuria after
      two revision surgeries of the penile prosthesis. RESULTS: The inflatable penile
      prosthesis reservoir migrated into the bladder. A new reservoir was repositioned
      on the contralateral side to the erosion site with salvage surgery. CONCLUSIONS:
      Erosion of penile prosthesis reservoir into the bladder due to shortened tubing
      by multiple revision surgeries is rare. In selected cases, reposition of a new
      reservoir on the contralateral side to the erosion site can be used as salvage
      surgery.

PMID- 16422835
TI  - Commentaries on Jackson et al. "Successful withdrawal of oral long-acting
      nitrates to facilitate phosphodiesterase type 5 inhibitor use in stable coronary
      disease patients with erectile dysfunction".

PMID- 16422836
TI  - Persistent sexual arousal syndrome.

PMID- 16422837
TI  - Persistent sexual arousal syndrome--a descriptive study.

PMID- 16422840
TI  - Sensitivity of the psychological and interpersonal relationship scales to oral
      therapies for erectile dysfunction.
AB  - INTRODUCTION: Studies of erectile dysfunction (ED) therapies typically assess
      erectile function end- points, although other treatment outcomes may also be of
      value to men and their partners. Aim. To examine the treatment sensitivity of the
      Psychological and Interpersonal Relationship Scales (PAIRS) associated with the
      use of two phosphodiesterase type 5 (PDE5) inhibitors with different duration of
      action. METHODS: Men with ED were recruited from three clinical trials of
      tadalafil and sildenafil citrate to complete post-treatment questionnaires that
      included the PAIRS. In study 1, the PAIRS was assessed after 6 months of open
      label tadalafil (20 mg) treatment and after 2 months of real-world sildenafil use
      (25-100 mg). In studies 2 and 3, the PAIRS was assessed at the end of the trial
      assessment phase. In study 2, men with a 6-24 week history of sildenafil use (25
      100 mg) received 3 weeks of open-label sildenafil treatment (dosage at study
      entry), and then switched to 9 weeks of tadalafil treatment. In study 3, a double
      blind, crossover study, men were randomized to 12 weeks of either tadalafil (20
      mg) or sildenafil (50 mg) treatment, followed by 12 weeks of the alternate
      treatment; PAIRS scores for the second treatment period were evaluated. MAIN
      OUTCOME MEASURE: Treatment outcomes were assessed with the PAIRS, a new reliable
      and valid self-report measure of sexual self-confidence, spontaneity, and time
      concerns before sex. RESULTS: Significant mean differences were observed on all
      PAIRS domain scores associated with tadalafil and sildenafil treatment. Across
      studies, men had significantly higher sexual self-confidence and spontaneity
      scores, and lower time concerns scores in reference to tadalafil compared with
      their scores in reference to sildenafil. CONCLUSIONS: Mean differences observed
      on PAIRS domains across studies support the sensitivity of the measure to
      differentiate between these two ED treatments.

PMID- 16422841
TI  - The use of the sexual function questionnaire as a screening tool for women with
      sexual dysfunction.
AB  - AIM: To determine if the validated Sexual Function Questionnaire (SFQ), developed
      to assess efficacy in female sexual dysfunction (FSD) clinical trials, may also
      have utility in identifying target populations for such studies. METHODS: Data
      from five clinical trials and two general population surveys were used to analyze
      the utility of the SFQ as a tool to discriminate between the presence of specific
      components of FSD (i.e., hypoactive sexual desire disorder, female sexual arousal
      disorder, female orgasmic disorder, and dyspareunia). RESULTS:
      Sensitivity/specificity analysis and logistic regression analysis, using data
      from all five clinical studies and the general population surveys, confirmed that
      the SFQ domains have utility in detecting the presence of specific components of
      FSD and provide scores indicative of the presence of a specific sexual disorder.
      CONCLUSIONS: The SFQ is a valuable new tool for detecting the presence of FSD and
      identifying the specific components of sexual functions affected (desire,
      arousal, orgasm, or dyspareunia).

PMID- 16422842
TI  - Cyclic nucleotide signaling in cavernous smooth muscle.
AB  - INTRODUCTION: Penile erection depends on cavernous smooth muscle relaxation that
      is principally regulated by cyclic nucleotide signaling. It is hoped that a
      comprehensive review of publications relevant to this subject will be helpful to
      both scientists and clinicians who are interested in the sciences of erectile
      function/dysfunction. AIMS. To review the roles of extracellular signaling
      molecules, their receptors, intracellular effectors, and phosphodiesterases in
      cyclic nucleotide signaling that leads to cavernous smooth muscle relaxation. The
      involvement of these molecules in the development of erectile dysfunction and the
      possibility of using them as therapeutic agents or targets are also discussed.
      METHODS: Entrez, the search engine for life sciences, was used to search for
      publications relevant to the topics of this review. Keywords used in the searches
      included vascular, cavernous, penis, smooth muscle, signaling molecules
      (adenosine, nitric oxide, etc.), and key elements in the cyclic nucleotide
      signaling pathways (cAMP, cGMP, cyclases, PKG, PKA, etc.). Articles that are
      dedicated to the study of erectile function/dysfunction were prioritized for
      citation. RESULTS: More than 1,000 articles were identified, many of which are
      studies of the vascular system and are therefore reviewed but not cited. Studies
      on erectile function have identified both cyclic adenosine monophosphate (cAMP)
      and cyclic guanosine monophosphate (cGMP) signaling pathways in cavernous smooth
      muscle. Many signaling molecules of these two pathways have been shown capable of
      inducing erection when administered intracavernously. However, for sexually
      induced erection, nitric oxide (NO) is the responsible signaling molecule and it
      passes on the signal through soluble guanyl cyclase (sGC), cGMP, and protein
      kinase G (PKG). CONCLUSIONS: The NO/sGC/cGMP/PKG pathway is principally
      responsible for sexually stimulated erection. Detumescence is mainly carried out
      by the degradation of cGMP by phosphodiesterase 5. Both cAMP and cGMP signaling
      pathways are susceptible to genetic and biochemical alterations in association
      with erectile dysfunction. Several key elements along these pathways are
      potential therapeutic targets.

PMID- 16422843
TI  - A multinational population survey of intravaginal ejaculation latency time.
AB  - INTRODUCTION: Intravaginal ejaculation latency time (IELT), defined as the time
      between the start of vaginal intromission and the start of intravaginal
      ejaculation, is increasingly used in clinical trials to assess the amount of
      selective serotonin reuptake inhibitor-induced ejaculation delay in men with
      premature ejaculation. Prospectively, stopwatch assessment of IELTs has superior
      accuracy compared with retrospective questionnaire and spontaneous reported
      latency. However, the IELT distribution in the general male population has not
      been previously assessed. AIM: To determine the stopwatch assessed-IELT
      distribution in large random male cohorts of different countries. METHODS: A
      total of 500 couples were recruited from five countries: the Netherlands, United
      Kingdom, Spain, Turkey, and the United States. Enrolled men were aged 18 years or
      older, had a stable heterosexual relationship for at least 6 months, with regular
      sexual intercourse. The surveyed population were not included or excluded by
      their ejaculatory status and comorbidities. This survey was performed on a
      "normal" general population. Sexual events and stopwatch-timed IELTs during a 4
      week period were recorded, as well as circumcision status and condom use. MAIN
      OUTCOME MEASURES: The IELT, circumcision status, and condom use. RESULTS: The
      distribution of the IELT in all the five countries was positively skewed, with a
      median IELT of 5.4 minutes (range, 0.55-44.1 minutes). The median IELT decreased
      significantly with age, from 6.5 minutes in the 18-30 years group, to 4.3 minutes
      in the group older than 51 years (P<0.0001). The median IELT varied between
      countries, with the median value for Turkey being the lowest, i.e., 3.7 minutes
      (0.9-30.4 minutes), which was significantly different from each of the other
      countries. Comparison of circumcised (N=98) and not-circumcised (N=261) men in
      countries excluding Turkey resulted in median IELT values of 6.7 minutes (0.7
      44.1 minutes) in circumcised compared with 6.0 minutes (0.5-37.4 minutes) in not
      circumcised men (not significant). The median IELT value was not affected by
      condom use. CONCLUSION: The IELT distribution is positively skewed. The overall
      median value was 5.4 minutes but with differences between countries. For all five
      countries, median IELT values were independent of condom usage. In countries
      excluding Turkey, the median IELT values were independent of circumcision status.

PMID- 16422844
TI  - Proposal for a definition of lifelong premature ejaculation based on
      epidemiological stopwatch data.
AB  - INTRODUCTION: Consensus on a definition of premature ejaculation has not yet been
      reached because of debates based on subjective authority opinions and
      nonstandardized assessment methods to measure ejaculation time and ejaculation
      control. AIM: To provide a definition for lifelong premature ejaculation that is
      based on epidemiological evidence including the neurobiological and psychological
      approach. METHODS: We used the 0.5 and 2.5 percentiles as accepted standards of
      disease definition in a skewed distribution. We applied these percentiles in a
      stopwatch-determined intravaginal ejaculation latency time (IELT) distribution of
      491 nonselected men from five different countries. The practical consequences of
      0.5% and 2.5% cutoff points for disease definition were taken into consideration
      by reviewing current knowledge of feelings of control and satisfaction in
      relation to ejaculatory performance of the general male population. MAIN OUTCOME
      MEASURES: Literature arguments to be used in a proposed consensus on a definition
      of premature ejaculation. RESULTS: The stopwatch-determined IELT distribution is
      positively skewed. The 0.5 percentile equates to an IELT of 0.9 minute and the
      2.5 percentile an IELT of 1.3 minutes. However, there are no available data in
      the literature on feelings of control or satisfaction in relation to ejaculatory
      latency time in the general male population. Random male cohort studies are
      needed to end all speculation on this subject. Exact stopwatch time assessment of
      IELT in a multinational study led us to propose that all men with an IELT of less
      than 1 minute (belonging to the 0.5 percentile) have "definite" premature
      ejaculation, while men with IELTs between 1 and 1.5 minutes (between 0.5 and 2.5
      percentile) have "probable" premature ejaculation. Severity of premature
      ejaculation (nonsymptomatic, mild, moderate, severe) should be defined in terms
      of associated psychological problems. CONCLUSION: We define lifelong premature
      ejaculation as a neurobiological dysfunction with an unacceptable increase of
      risk to develop sexual and psychological problems anywhere in a lifetime. By
      defining premature ejaculation from an authority-defined disorder into a
      dysfunction based on epidemiological evidence it is possible to establish
      consensus based on epidemiological evidence. Additional epidemiological stopwatch
      studies are needed for a final decision of IELT values at both percentile cutoff
      points.

PMID- 16422846
TI  - Successful withdrawal of oral long-acting nitrates to facilitate
      phosphodiesterase type 5 inhibitor use in stable coronary disease patients with
      erectile dysfunction.
AB  - INTRODUCTION: Vascular disease is the most common cause of male erectile
      dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors are effective in up
      to 80% of men but are contraindicated in the presence of oral nitrates, because
      of a potentially severe hypotensive interaction. AIMS: To see if stable coronary
      disease patients with ED could have their oral nitrates discontinued to allow
      safe use of a PDE5 inhibitor. METHODS: Prospective study of 425 men with ED and
      cardiac disease conducted in an outpatient cardiac sexual advice clinic. MAIN
      OUTCOME MEASURES: Discontinuation of oral nitrates to facilitate subsequent use
      of PDE5 therapy. RESULTS: Oral nitrates were being used by 88 (21%) coronary
      artery disease patients all of whom were clinically stable. Fifty-five (63%) of
      these men with a good exercise ability had their nitrates discontinued in the
      presence of continuing beta-blockade or calcium antagonist therapy. They were
      reviewed 1 week later. Only three restarted their nitrate therapy because of an
      increase in symptoms. Forty-nine of the 52 men no longer taking nitrates were
      treated with a PDE5 inhibitor which was effective in 22 out of 26 (85%) patients
      who have completed follow-up. Fifteen patients are currently undergoing clinic
      follow-up in order to optimize treatment, and nine patients have continued
      therapy with their family doctors. Importantly, there have been no adverse
      cardiac events. CONCLUSION: Oral nitrates can be discontinued in the presence of
      continuing beta-blockade and/or calcium antagonist therapy in stable coronary
      disease patients with ED to allow for the safe use of PDE5 inhibitors.

PMID- 16422845
TI  - Premature ejaculation--does country of origin tell us anything about etiology?
AB  - INTRODUCTION: Premature ejaculation is a common sexual problem. The etiology of
      this condition is unclear. It has been suggested that some racial groups may be
      more at risk than others. We had a clinical impression that in our unit in
      London, UK, there was a preponderance of men from Islamic and Asian backgrounds.
      AIM: We therefore undertook a retrospective analysis of our clinic population
      over an eighteen-month period. METHODS: A total of 123 patients were identified
      with a clinical diagnosis of PE based on the DSM-IV and UK national guidelines.
      MAIN OUTCOME MEASURE: Demographic and clinical data were collected
      retrospectively: parameters of patients seen in the previous 18 months were
      identified, including self-identified ethnicity and age. Patient-defined
      ethnicity was compared with the ethnicity of self-referring patients attending
      our general sexual health services (outpatients), and also with local population
      census data. RESULTS: A total of 60% of patients were from Islamic or Asian
      backgrounds but 12% and 11% came from those racial groups in local population
      census data and our general clinic population respectively (P<0.001).
      CONCLUSIONS: It thus appears that there is a preponderance of men from Islamic
      and Asian backgrounds presenting to our unit with premature ejaculation. The
      reasons for this are unclear. Possible mechanisms include psychosocial, familial,
      or genetic influences.

PMID- 16422847
TI  - The efficacy of tadalafil in clinical populations.
AB  - OBJECTIVES: To evaluate the efficacy of tadalafil in men with erectile
      dysfunction (ED) by demographic and ED characteristics, in patients having
      various comorbid medical conditions, and in patients receiving drug treatment for
      other medical conditions. METHODS: This is an analysis of 11 double-blind,
      placebo-controlled trials with 2,102 men with a broad spectrum of ED etiology and
      various comorbid medical conditions as participants. The variables analyzed in
      this report included race, age, body mass index (BMI), ED etiology, ED severity,
      ED duration, smoking, prior sildenafil use, presence of comorbid conditions
      (diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia,
      depression, benign prostatic hyperplasia), and treatment with antihypertensives
      or antidepressants. Patients were randomly assigned to receive tadalafil 10 mg
      (N=321), tadalafil 20 mg (N=1,143), or placebo (N=638). The primary efficacy
      variables included mean changes from baseline in the erectile function (EF)
      domain score of the International Index of Erectile Function (IIEF)
      questionnaire, and the mean per-patient percentage of "yes" responses to the
      Sexual Encounter Profile (SEP) diary question 3 (SEP3--successful intercourse).
      The Global Assessment Question 1 (GAQ) was evaluated, as was the percentage of
      men attaining a normal IIEF EF domain score at end point. RESULTS: Patients
      taking tadalafil 10 mg or 20 mg demonstrated significant improvement (P<0.005)
      from baseline to end point on the IIEF EF domain score in all subpopulations
      analyzed compared with patients receiving placebo. The mean-per-patient
      percentage of "yes" responses to SEP3 increased significantly in all
      subpopulations taking tadalafil compared with placebo (P<0.05). Tadalafil-treated
      patients had a significantly greater positive response rate on the GAQ in all
      subpopulations analyzed compared with placebo-treated patients (P<0.03) except
      for the tadalafil 10 mg cardiovascular subpopulation (placebo, 46.8%; tadalafil
      10 mg, 71.0%; P=0.127). The percentage of positive responses ranged from 72% to
      91% for patients on tadalafil 20 mg and from 52% to 94% for tadalafil 10 mg
      compared with a range of 20% to 47% for placebo-treated patients. CONCLUSIONS:
      Tadalafil was effective in improving erectile function across a wide spectrum of
      ED patients including patients with various comorbid conditions.

PMID- 16422848
TI  - The use of an erectogenic pharmacotherapy regimen following radical prostatectomy
      improves recovery of spontaneous erectile function.
AB  - PURPOSE: It has been suggested that postradical prostatectomy (RP) erectile
      function outcomes are improved by early use of erectogenic medications. This
      analysis was designed to assess the ability of a post-RP vasoactive drug program
      to improve long-term spontaneous erectile function. METHODS: Men with functional
      preoperative erections who underwent RP were challenged early postoperatively
      with oral sildenafil. Nonresponders were switched to intracavernosal injection
      therapy (ICI). Patients were instructed to inject three times a week. Only
      patients who presented within 6 months post RP, who completed the International
      Index of Erectile Function (IIEF) questionnaire on at least three separate
      occasions after surgery, and who had been followed for at least 18 months were
      included. Data from men who were committed to rehabilitation were compared with
      those of men who did not follow the protocol but continued to be followed
      serially following RP. RESULTS: There were 58 patients in the rehabilitation (R)
      group and 74 in the nonrehabilitation (NR) group. No differences existed in mean
      patient age, comorbidity profile, intraoperative nerve sparing status, or
      postoperative erectile hemodynamics between the two groups. At 18 months post RP,
      there were statistically significant differences between the two groups in the
      percentage of patients who were capable of having medication-unassisted
      intercourse (R=52% vs. NR=19%, P<0.001); mean erectile rigidity (R=53+/-21% vs.
      NR=26+/-43%, P<0.01); mean IIEF erectile function (EF) domain scores (R=22+/-6
      vs. NR=12+/-14, P<0.01); the percentage of patients with normal EF domain scores
      (R=22% vs. NR=6%, P<0.01); the percentage of patients responding to sildenafil
      (R=64% vs. NR=24%, P<0.001); the time to become a sildenafil responder (R=9+/-4
      vs. NR=13+/-3 months, P=0.02); and the percentage of patients responding to ICI
      (R=95% vs. NR=76%, P<0.01). CONCLUSIONS: The data generated from this
      nonrandomized study indicate that a pharmacologic penile rehabilitation protocol
      results in higher rates of spontaneous functional erections and erectogenic drug
      response after RP.

PMID- 16422852
TI  - Association between erectile dysfunction and sleep disorders measured by self
      assessment questionnaires in adult men.
AB  - BACKGROUND: Erectile dysfunction (ED) is often associated with sleep disorders
      and sleep apnea syndrome (SAS) in mostly middle-aged and elderly men. Sleep
      disorders and ED are also prevalent in younger men. PURPOSE: To study the
      association between ED, sleep disorders, and SAS, particularly among adult men.
      METHODS: A health screening program is offered by the Israel Defense Force (IDF)
      for career servicemen older than 25 years, for the purpose of early detection of
      ED and sleep disorders, among other concealed morbidities. The Sexual Health
      Inventory for Man questionnaire (SHIM) was used to measure ED. The Sleep Quality
      (SQ) questionnaire, developed by the medical services of the IDF, was used to
      characterize SAS and other sleep disorders. RESULTS: From 2002 through 2003,
      3,363 men (mean age, 36.1+/-6.8 years) replied to the SHIM and SQ questionnaires.
      Of these men, 337 (10%) scored high (>or=25) in the SQ questionnaire, suggesting
      moderate to severe sleep disorders, and 870 men (25.8%) scored low (<or=21) in
      the SHIM questionnaire, suggesting ED. There was a negative correlation between
      the scores in the SHIM questionnaire and in the SQ questionnaire (r=-0.29,
      P<0.0001)-even after age adjustment and after excluding men with risk factors for
      both ED and SAS (such as essential hypertension, diabetes mellitus, and obesity;
      r=-0.21, P<0.0001). This correlation was consistent with all severity levels of
      ED and sleep disorders. CONCLUSIONS: Sleep disorders, in particular SAS, and ED
      are prevalent and may be related in adult men. Either ED or sleep disorders
      should be considered whenever the other is suspected in adult men. Sleep
      disorders and ED should also be investigated for the purpose of treating
      underlying systemic diseases and emotional disorders, and in order to prevent
      late complications of atherosclerosis.

PMID- 16422853
TI  - Pattern of endocrinal changes in patients with sexual dysfunction.
AB  - INTRODUCTION: Many patients with endocrinal changes (endocrinopathy) have some
      degrees of sexual dysfunction that necessitate assessment and treatment. AIM: To
      assess the prevalence, and identify the pattern, of endocrinopathy in patients
      with sexual dysfunction in our community. METHODS: A total of 1,248 male patients
      with sexual dysfunction were enrolled in this study. Patients were screened for
      erectile dysfunction (ED) and sexual desire by the erectile function and the
      sexual desire domains of the International Index of Erectile Function (IEEF).
      Patients underwent routine laboratory investigations as well as total
      testosterone and prolactin assessment. All patients were referred to an
      endocrinologist for clinical and biochemical assessment of their endocrine
      function. The evaluation consisted of comprehensive history taking, physical
      examination, and, as needed, laboratory investigations. RESULTS: Mean ages+/-SD
      were 51.9+/-12.2 and 52.3+/-11.7 years for patients with and without
      endocrinopathy, respectively. Of the study population, 23.8% had endocrinopathy.
      The most frequent endocrinal changes were low testosterone level (15%),
      hyperprolactinemia (13.7%), and hypothyroidism (3.1%). There were significant
      associations between endocrinopathy and obesity, smoking, low desire, and
      premature ejaculation (P<0.05 for each). Also, significant associations were
      found between low desire and low testosterone level, hyperprolactinemia, and
      hypothyroidism (P<0.05 for each). Hyperprolactinemia was significantly associated
      with premature ejaculation (P<0.05) but not with low testosterone level (P>0.05).
      There was no significant association between endocrinopathy and age, cigarette
      smoking (number and duration), and ED (duration, severity, type of onset, and
      progression) (P>0.05 for each). CONCLUSION: Endocrinopathy is not a rare
      condition among ambulatory patients with sexual dysfunction. This study provides
      a quantitative estimate of endocrinopathy in ambulatory patients with sexual
      dysfunction.

PMID- 16422854
TI  - Testosterone therapy can enhance erectile function response to sildenafil in
      patients with PADAM: a pilot study.
AB  - INTRODUCTION: Recent studies suggest a direct relationship between free
      testosterone and cavernous vasodilatation. Some men with erectile dysfunction
      (ED) associated with PADAM (partial androgen deficiency in aging men) might
      possibly benefit from testosterone undecanoate therapy (TRT). OBJECTIVES: To
      determine the efficacy of testosterone undecanoate in facilitating the erectile
      response and patient satisfaction with sildenafil in men 40-70 years old with
      PADAM symptoms. DESIGN AND METHODS: Prospective study including 40 patients
      recruited after a sildenafil therapeutic trial. Total testosterone and sex
      hormone binding globulin (SHBG) were measured to calculate the free androgen
      index. Prostate specific antigen (PSA) was measured and repeated 2 months after
      treatment. A rating score was used for PADAM symptoms, and the 5-point
      abbreviated version of the International Index of Erectile Function (IIEF-5) to
      assess erectile function. Men failing to respond to sildenafil were randomized
      into two groups receiving sildenafil plus continuous TRT (group 1ST), and TRT
      (group 1T) alone. Men partially responding to sildenafil were randomized into two
      groups receiving sildenafil plus continuous TRT for 2 months (group 2ST), or
      sildenafil alone (group 2S). Treatment efficacy was assessed by analysis of
      between-group differences. RESULTS: Groups 1T, 2S, and 2ST showed significant
      improvement in PADAM scores (P<0.05, Wilcoxon matched pairs test). Patients
      receiving both sildenafil plus continuous TRT (groups 1ST and 2ST) showed
      significant improvement in IIEF-5 scores (P<0.5, paired t-test). No significant
      changes in serum levels of PSA were detected (paired t-test). CONCLUSIONS: We
      conclude that TRT appears to be beneficial and safe in facilitating the erectile
      response and patient satisfaction with sildenafil in men with PADAM symptoms.
      Androgen supplementation should be carried out cautiously with careful monitoring
      to avoid possible adverse effects.

PMID- 16422855
TI  - Antibiotic coating reduces penile prosthesis infection.
AB  - AIM: To evaluate the efficacy of a new antibiotic-coated (rifampicin+monocycline)
      penile prosthesis in prevention of bacterial adhesion and reduction of penile
      prosthesis infection. METHODS: In a retrospective analysis of medical records of
      men who had undergone implantation of American Medical Systems (AMS) inflatable
      penile prostheses between July 1990 and November 2003, we compared patients with
      AMS antibiotic-coated prostheses and patients with AMS nonantibiotic-coated
      prostheses. A total of 152 men aged from 27 to 79 years with erectile dysfunction
      underwent implantation of the AMS inflatable penile prosthesis. Fifty-eight
      patients received the antibiotic-coated prosthesis between July 2001 and November
      2003, and 94 patients received the nonantibiotic-coated prosthesis between July
      1990 and June 2001. RESULTS: In most cases infection was present; it was detected
      1-2 days or up to 3-6 months after implantation. Complications including
      infection, which required surgical intervention, were observed in 15 patients of
      the nonantibiotic-coated prosthesis group (three reoperations for infection), and
      noninfection-related failure in five patients of the antibiotic-coated prosthesis
      group. In the nonantibiotic-coated prosthesis group of patients, time to
      infection ranged from 1 day to 6 months (mean 3.5 months). The antibiotic-coated
      prosthesis group of patients immediately after surgery and during the short- and
      intermediate-term follow-up had no infection of the penile prosthesis.
      CONCLUSIONS: We suggest that the antibiotic locally delivered from the prosthesis
      coating might be an effective supplement for prevention of prosthesis-related
      infection in penile prosthesis surgery.

PMID- 16422856
TI  - A history of sexual medicine in the United kingdom.
AB  - The history of sexual medicine in the United Kingdom since the 19th century is
      reviewed, with particular reference to masturbation, homosexuality,
      contraception, and in the past four decades, the treatment of sexual dysfunction.
      The medical profession's tendency to deal with sexual issues according to the
      sociopolitical and moral issues of the time is emphasized, and whereas "sex
      negativism" has prevailed within the medical profession for most of this
      historical period, there has been a succession of individuals within the
      profession who have presented a more positive approach to defining and promoting
      sexual health. Four tracks within sexual medicine over the past 30 years are
      described: the psychoanalytic approach of the Institute of Psychosexual Medicine,
      modern "sex therapy," psychophysiological sex research, and the involvement of
      andrology in the assessment and treatment of erectile dysfunction. The impact of
      Viagra is seen as the most recent chapter in this history.

PMID- 16422857
TI  - Association between erectile dysfunction and coronary artery disease: a case
      report study.
AB  - Evidence is accumulating in favor of classifying erectile dysfunction (ED) as a
      vascular disorder. There are three main clinical scenarios in which ED and
      coronary artery disease (CAD) may coexist: the patient with ED who later develops
      CAD, the patient with overt CAD who is casually found to have ED, and the patient
      with acute coronary syndrome who has normal sexual function. This study presents
      three cases and discusses a "putative" pathophysiological mechanism underlying
      all these clinical presentations. Further studies, coupling functional and
      structural changes of coronary circulation with those of penile (i.e., dynamic
      penile test) circulation in each of these situations are mandatory to support
      this hypothesis.

PMID- 16422859
TI  - Comments from Ronald Virag on intracavernous injection: 25 years later.

PMID- 16422860
TI  - Assessment and management of women's sexual dysfunctions: problematic desire and
      arousal.
AB  - INTRODUCTION: Women frequently report low sexual desire or interest. An
      associated lack of subjective arousal during sexual activity is clinically highly
      apparent but has not been the focus of traditional sexual inquiry, definitions of
      dysfunction, or management. The frequent poor correlation of women's subjective
      sexual arousal and observable increases in genital congestion in response to
      sexual stimulation has not been reflected in assessment, diagnosis, or
      management. AIM: To provide recommendations/guidelines for the assessment and
      management of women's sexual dysfunctions focusing on low desire, low interest,
      and lack of arousal. METHODS: An international consultation, in collaboration
      with major sexual medicine associations, assembled over 200 multidisciplinary
      experts from 60 countries into 17 committees. One subcommittee of five members
      focused on women's sexual desire and arousal, developing over a 2-year period
      various recommendations. MAIN OUTCOME MEASURE: Expert opinion was based on
      grading of evidence-based scientific literature, widespread internal committee
      discussion, public presentation, and debate. RESULTS: Women's sexual response in
      health can be reconceptualized as a circular model of overlapping phases of
      variable order influenced by psychological, societal, and biological factors.
      Subsequent revisions to definitions of arousal and desire disorder are given.
      Recommendations regarding assessment and management focus on factors reducing
      arousability and satisfaction. These include women's mental health and feelings
      for their partner, generally and at the time of sexual activity. Recommendations
      reflect the poor correlation of subjective arousal and increases in genital
      vasocongestion. CONCLUSION: Further outcome research of management based on new
      conceptualization of sexual response and revised definitions of dysfunction is
      needed. The basis of the variable correlation between genital vasocongestion and
      subjective arousal needs clarification as do the biological underpinnings of
      sexual response and their changes with age and life cycle.

PMID- 16422861
TI  - Women's sexual pain and its management.
AB  - INTRODUCTION: Approximately 15% of women have chronic dyspareunia that is poorly
      understood, infrequently cured, often highly problematic, and distressing.
      Chronic dyspareunia is an urgent health issue. AIM: To provide
      recommendations/guidelines concerning state-of-the-art knowledge for the
      assessment and management of women's sexual pain disorders. METHODS: An
      international consultation, in collaboration with the major sexual medicine
      associations, assembled over 200 multidisciplinary experts from 60 countries into
      17 committees. One six-member committee focused on women's sexual pain disorders,
      developing recommendations over a 2-year period. MAIN OUTCOME MEASURE: Expert
      opinion was based on grading of evidence-based medical literature, widespread
      internal committee discussion, public presentation, and debate. RESULTS: There is
      increasing evidence for the role of neuropathic pain mechanisms in the
      pathophysiology of sexual pain disorders. Empirical literature has demonstrated
      the comorbid presence of clinical psychopathology. With regard to the
      pathophysiologic role of the pelvic floor and sexual pain disorders, studies
      reveal that (i) differentiation between vaginismus and dyspareunia using clinical
      tools is difficult; (ii) vaginal spasms have not been identified; (iii) physical
      therapists can differentiate vaginismic women from matched controls based on
      muscle tone/strength differences; (iv) the traditional treatment of vaginismus
      with vaginal "dilatation" plus psycho-education, desensitization, and so forth is
      not evidence-based; (v) pelvic floor muscle tone/strength measures for women
      suffering from vulvar vestibulitis syndrome are intermediate between those of
      women with vaginismus and no-pain controls; and (vi) the pelvic floor musculature
      is indirectly innervated by the limbic system and highly reactive to emotional
      stimuli and states. Pelvic floor therapies for dyspareunia may be effective.
      CONCLUSION: Recommendations include (i) revising the definitions of vaginismus
      and dyspareunia; (ii) integration of treatment approaches; (iii) validation of
      nonspecific treatment effects; (iv) controlled studies to test interventions; and
      (v) sexuality education to help prevent sexual pain.

PMID- 16422862
TI  - The impact of aging on sexual function and sexual dysfunction in women: a review
      of population-based studies.
AB  - INTRODUCTION: Scientific interest in the impact of aging on women's sexual
      function and dysfunction has increased in the half century since Kinsey described
      age-related changes in women's sexual activities. However, a range of
      methodological issues limit the conclusions that can be drawn from many published
      studies in this area. AIM: To review community-based studies investigating
      changes in women's sexual function and sexual dysfunction with age, taking into
      account confounders to aging and methodological limitations. METHODS: Electronic
      databases were searched for published studies investigating changes in sexual
      function and dysfunction with age. A critical review was carried out. MAIN
      OUTCOME MEASURES: Age-related changes in sexual function and dysfunction.
      RESULTS: There are inconsistencies in the way sexual function and sexual
      dysfunction are measured. Validated scales are infrequently used. Low response
      rates, limited age ranges, and restrictive inclusion criteria limit the
      generalizability of many studies. Confounders are often either not measured or
      not analyzed. Longitudinal studies are rare, making it difficult to separate the
      effects of birth cohort and aging. The evidence indicates that a woman's sexual
      function declines with age. This decline begins in a woman's late 20s to late
      30s. Specifically, desire, frequency of orgasm, and frequency of sexual
      intercourse decrease with age. However, it is not clear whether arousal decreases
      or remains relatively constant. In longitudinal studies, decline in women's
      sexual function has also been detected, but patterns of stability and improved
      sexual function have also been observed for short periods of time. The prevalence
      of most sexual difficulties or dysfunctions changes little with age, with the
      exception of sexual pain, which may decrease. CONCLUSIONS: Age-related changes in
      sexually related personal distress may help explain why the prevalence of sexual
      dysfunctions remains constant with age while sexual function declines. More
      research is needed to demonstrate this.

PMID- 16422863
TI  - Persistent sexual arousal syndrome: a descriptive study.
AB  - INTRODUCTION: Persistent sexual arousal disorder (PSAS) is a poorly documented
      condition characterized by persistent genital arousal in the absence of conscious
      feelings of sexual desire. AIM: To determine whether there are replicable
      features associated with PSAS, to describe salient characteristics of women
      reporting this condition, and to determine predictors of distress. METHODS: A 46
      item Internet survey containing demographic information, symptom description,
      triggers, exacerbation and relief measures, distress ratings, and life and sexual
      satisfaction was placed on a secure server. MAIN OUTCOME MEASURES: Frequency
      analyses of descriptive data, and stepwise multiple regression analysis to
      identify independent predictors of level of distress. RESULTS: Of the 103
      respondents, most were in good health, well educated, and in long-term
      relationships. Ninety-eight percent of respondents met at least one criterion for
      PSAS and 53% met all five criteria. Involuntary genital and clitoral arousal
      persisting for extended time periods, genital arousal unrelated to subjective
      feelings of sexual desire, and genital arousal not relieved with orgasms were the
      most frequently endorsed features associated with this syndrome. Symptom triggers
      included sexual stimulation, masturbation, stress, and anxiety. Distress about
      the condition was low in 25%, moderate in 35%, and high in 40% of respondents.
      The strongest predictors of distress were intrusive and unwanted feelings of
      genital arousal (P < 0.0001), continuous symptoms (P < 0. 001), feelings of
      unhappiness (P < 0.03), shame (P = 0.0001) and worry (P = 0.01), reduced sexual
      satisfaction (P < 0.004), enjoyment of symptoms some of the time (P = 0.01), and
      relationship status (P < 0.004). CONCLUSIONS: The results of this research
      support the description of a condition (persistent sexual arousal) involving
      involuntary genital and clitoral arousal unrelated to subjective feelings of
      sexual desire which persists despite one or more orgasms and which usually feels
      intrusive and unwanted. Varying levels of distress were identified with this
      condition as well as a variety of primarily negative emotional reactions.

PMID- 16422864
TI  - Persistent sexual arousal syndrome associated with increased soy intake.
AB  - INTRODUCTION: Persistent sexual arousal syndrome is an uncommon sexual complaint.
      Patients with this disorder can be distressed by the escalation of tension in the
      pelvic region and the prevailing necessity to diminish the pressure by self
      stimulation. Patients frequently suffer from guilt or shame and often do not seek
      medical care. There are many potential causes of this disorder; however, a
      definitive etiology has yet to be elucidated. CASE: The patient is a 44-year-old
      female who presented to her gynecologist for evaluation of dysmenorrhea and
      menometrorrhagia. During the review of systems, the patient reported 5-6 months
      of increased pelvic tension, not associated with an increase in desire that
      required her to self-stimulate to orgasm approximately 15 times daily. Upon
      further inquiry, the patient disclosed that her dietary regimen included soy
      intake in excess of 4 pounds per day that began approximately 1 month prior to
      the onset of symptoms. RESULTS: Treatment consisted of supportive counseling and
      dietary modification. At the 3-month follow-up visit, the patient's menstrual
      difficulties and sexual complaints resolved. CONCLUSIONS: Although no known cause
      or cure of persistent sexual arousal syndrome has been identified to date, the
      success of reducing dietary of phytoestrogens in this patient may provide insight
      into the etiology of the disorder and suggest potential treatments.

PMID- 16422865
TI  - Enhancement of both EDHF and NO/cGMP pathways is necessary to reverse erectile
      dysfunction in diabetic rats.
AB  - AIMS AND METHODS: Phosphodiesterase 5 (PDE5) inhibitors are less effective in the
      treatment of erectile dysfunction (ED) in diabetic men than in nondiabetic
      patients. We have evaluated the effects of sildenafil, a PDE5 inhibitor that
      enhances the nitric oxide (NO)/cGMP pathway, calcium dobesilate (DOBE), which
      potentiates endothelium-derived hyperpolarizing factor (EDHF)-mediated responses
      and the combination of both on erectile responses elicited by cavernosal nerve
      electrical stimulation (CNES) in a rat model of ED after 8 weeks of
      streptozotocin-induced diabetes. RESULTS: After 8 weeks of diabetes, erectile
      responses to CNES were significantly decreased in diabetic animals compared with
      nondiabetic time controls. While intravenous administration of sildenafil (0.3
      mg/kg) or DOBE (10 mg/kg), individually, enhanced erectile responses in
      nondiabetic rats (214.7 +/- 34.1% and 268.5 +/- 30.1% of control response at 1
      Hz, respectively), each failed to significantly enhance erectile responses in
      diabetic rats. Only when administered in combination did DOBE and sildenafil
      markedly potentiate erectile responses in these animals (380.1 +/- 88.6% of
      control response at 1 Hz), completely restoring erectile function. CONCLUSIONS:
      These findings emphasize the importance of NO/cGMP and EDHF pathways for normal
      erectile function. They also give support to the in vitro observation that
      diabetes impairs NO and EDHF-dependent responses, precluding the complete
      recovery of erectile function with PDE5 inhibitors and explaining the relatively
      poor clinical response of diabetic men with ED to PDE5 inhibition. Finally, our
      study suggests that a pharmacological approach that combines enhancement of
      NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men.

PMID- 16422866
TI  - Age-related changes in phosphorylation of endothelial nitric oxide synthase in
      the rat penis.
AB  - AIM: Aging is associated with erectile dysfunction (ED) attributed to reduced
      nitric oxide synthase (NOS) activity and nitric oxide bioavailability. However,
      the mechanism for this effect has not been fully investigated. We evaluated (i)
      whether age-related ED involves dysregulation of endothelial NOS (eNOS)
      phosphorylation; and (ii) whether vascular endothelial growth factor (VEGF)
      exerts erectile effects and operates via eNOS phosphorylation in aged rats.
      METHODS: Male Fischer 344 "young" (4-month-old) and "aged" (19-month-old) rats
      were used. Electrical stimulation of the cavernous nerve (CNS) was performed to
      generate penile erection. Erectile response in the presence of rhVEGF165 was
      evaluated by intracavernosal pressure monitoring 25 minutes after intracavernosal
      injection of VEGF. Penes were excised at baseline, with or without rhVEGF
      treatment, and after CNS for Western immunoblot of phospho-eNOS (Ser-1177 and Thr
      495), phospho-Akt, and eNOS. RESULTS: Erectile response was significantly reduced
      in aged rats compared with young rats. Phospho-eNOS (Ser-1177) and phospho-Akt
      were significantly reduced, while phospho-eNOS (Thr-495) was significantly
      increased, in the aged penis at baseline and after CNS. rhVEGF significantly
      improved erection and reversed downregulated Ser-1177, but not upregulated Thr
      495 phosphorylation, on eNOS in aged penes. eNOS protein was significantly
      increased in aged penes. CONCLUSIONS: Age-related ED is associated with eNOS
      inactivation through a decrease in phosphorylation of its positive regulatory
      site (Ser-1177) and an increase in phosphorylation of its negative regulatory
      site (Thr-495) in the penis. Altered phosphorylation/constitutive activation of
      eNOS by fluid shear stress may be a major determinant of compromised vascular
      homeostasis of the aged penis. The finding that VEGF rapidly induces erection and
      partly corrects alterations in eNOS phosphorylation in the aged rat penis
      suggests impaired eNOS activation by deficient endogenous VEGF and supports the
      potential for growth factor therapy in the treatment of age-related ED.

PMID- 16422867
TI  - Premature ejaculation: an observational study of men and their partners.
AB  - INTRODUCTION: Premature ejaculation (PE) is the most common male sexual
      dysfunction affecting men and their partners. Lack of community-based data
      describing this condition limits understanding of PE and its outcomes. AIM: To
      characterize PE in a large population of men with and without PE using patient
      reported outcome (PRO) measures elicited from men and their partners. METHODS: 4
      week, multicenter, observational study of males (> or =18 years) and their female
      partners in monogamous relationships (> or =6 months). Screening, baseline, and
      follow-up visits scheduled at 2-week intervals. Clinicians diagnosed PE utilizing
      DSM-IV-TR criteria. Intravaginal ejaculatory latency time (IELT), measured by a
      stopwatch held by the partner, was recorded for each sexual intercourse
      experience. Subject and partner independently assessed PROs: control over
      ejaculation and satisfaction with sexual intercourse (0 = very poor to 4 = very
      good), personal distress and interpersonal difficulty (0 = not at all to 4 =
      extremely), and severity of PE (0 = none to 3 = severe). Results. Of the total
      study population (N = 1,587), 207 subjects were diagnosed with PE and 1,380 were
      assigned to the non-PE group. Median IELT (min) was 1.8 (range, 0-41) for PE and
      7.3 (range, 0-53) for non-PE subjects (P < 0.0001). More PE vs. non-PE subjects
      gave ratings of "very poor" or "poor" for control over ejaculation (72% vs. 5%; P
      < 0.0001) and satisfaction with sexual intercourse (31% vs. 1%; P < 0.0001). More
      subjects in the PE vs. non-PE group gave ratings of "quite a bit" or "extremely"
      for personal distress (64% vs. 4%; P < 0.0001) and interpersonal difficulty (31%
      vs. 1%; P < 0.0001). Subject and partner assessments showed similar patterns and
      correlated moderately (0.36-0.57). CONCLUSIONS: PE subjects reported
      significantly shorter IELT. Overlap in IELT distributions was observed between
      the PE and non-PE groups, indicating the need for additional PRO measures to
      characterize PE. Shorter IELT was significantly associated with reduced
      ejaculatory control and sexual satisfaction and increased distress and
      interpersonal difficulty.

PMID- 16422868
TI  - Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation.
AB  - OBJECTIVES: Premature ejaculation (PE) is the most common ejaculatory
      dysfunction. We assessed the efficacy of sildenafil to increase the time to
      ejaculation, improve ejaculatory control, and decrease the postejaculatory
      erectile refractory time in men with PE. DESIGN AND METHODS: The main study was
      an 8-week, double-blind, placebo-controlled, parallel group study in men between
      18 and 65 years of age with diagnosed PE. A substudy was also conducted using a
      subset of patients (two-way crossover, one center) before entry to the main
      study. The primary study measured intravaginal ejaculatory latency (IELT) and
      responses to the Index of Premature Ejaculation (IPE) questionnaire. The substudy
      measured vibrotactile stimulation ejaculatory latency time (VTS-ELT) and
      postejaculatory erectile refractory time. Differences between treatment groups
      were determined by ancova at the 5% level of significance. RESULTS: The change in
      IELT (1.6 +/- 6.08 vs. 0.6 +/- 2.07 minutes) and VTS-ELT (2.9 +/- 0.4 vs. 2.4 +/-
      0.4 minutes) were higher after taking sildenafil, compared with placebo, but did
      not reach statistical significance. However, patients who took sildenafil (vs.
      placebo) reported significantly (P < 0.05) increased ejaculatory control (1.8 +/-
      0.3 vs. 1.5 +/- 0.3), increased ejaculatory confidence (2.2 +/- 0.2 vs. 1.9 +/-
      0.2), and improved overall sexual satisfaction scores (3.1 +/- 0.2 vs. 2.8 +/-
      02) on the IPE, and had a decreased postejaculatory erectile refractory time (3.2
      +/- 0.7 vs. 6.4 +/- 0.7 minutes). The most common adverse events for sildenafil
      (vs. placebo) were headache (15% vs. 1%), flushing (15% vs. 0%), dyspepsia (5%
      vs. 1%), abnormal vision (5% vs. 0%), and rhinitis (5% vs. 0%). CONCLUSIONS:
      Although IELT and VTS-ELT were not significantly improved, sildenafil increased
      confidence, the perception of ejaculatory control, and overall sexual
      satisfaction, and decreased the refractory time to achieve a second erection
      after ejaculation in men with PE.

PMID- 16422869
TI  - Premature ejaculation: prevalence and associated conditions in a sample of 12,558
      men attending the andrology prevention week 2001--a study of the Italian Society
      of Andrology (SIA).
AB  - INTRODUCTION: Premature ejaculation (PE) is the most frequent sexual complaint.
      AIM: To investigate prevalence of PE and its associated conditions. METHODS: We
      analyzed information gathered from men attending a free andrologic consultation
      in 186 Italian medical centers, in the setting of a project focused on andrologic
      prevention. MAIN OUTCOME MEASURES: Risk factors for PE. RESULTS: Five hundred
      sixty-nine men suffered from lifelong PE; 1,855 had previously normal
      ejaculation; and 234 had PE not specified. Men with PE were younger than those
      without, but after adjusting for concomitant erectile dysfunction the risk of PE
      significantly decreased with aging. Men more educated, or who had experienced a
      divorce had a slightly increased risk. Also, lifestyle and occupational status
      affected the risk of PE. Concerning medical history, a decreased risk of PE
      emerged in men with treated diabetes, and no association was found with
      hypertension, cardiopathy, hypercholesterolemia, and peripheral or central
      neuropathy. CONCLUSIONS: The results of the analysis of a large dataset show that
      subjects with PE who are seeking treatment either have experienced stress-related
      problems or have a physical condition predisposing to this dysfunction (genital
      anomalies, prostate inflammation).

PMID- 16422870
TI  - Psychosexual factors that differentiate men with inhibited ejaculation from men
      with no dysfunction or another sexual dysfunction.
AB  - AIM: Inhibited or retarded ejaculation (IE) is an uncommon male sexual
      dysfunction that may result in a lack of sexual fulfillment for both the man and
      his partner. In this study, we attempted to identify factors that differentiate
      men with IE from sexually functional controls or from men with other sexual
      dysfunctions and to specify whether such factors predict self-reported sexual
      arousal during psychophysiological assessment. METHODS: Each patient underwent
      psychophysiological assessment and a structured clinical interview based on a
      standardized questionnaire that included demographic information, psychosexual
      and medical history, and assessment of current sexual, erectile, and ejaculatory
      function, including relationship quality and characteristics. RESULTS: Men with
      IE resemble men with other dysfunctions but are differentiated from controls, in
      their lower level of relationship satisfaction, greater level of distress, and
      higher level of health-related problems. Men with IE were further characterized
      by lower levels of self-reported subjective sexual arousal, despite exhibiting
      strong penile response during psychophysiological testing and reporting high
      quality erections across a variety of situations. Also notable, however, were the
      many factors on which men with IE did not differ from controls. CONCLUSIONS:
      Taken together, this research helps specify directions for future investigations
      of men with IE.

PMID- 16422872
TI  - Attitudes of men with erectile dysfunction: a cross-national survey.
AB  - INTRODUCTION: Erectile dysfunction (ED), the inability to achieve or maintain an
      erection sufficient for sexual performance, is a complex disorder involving
      multiple biopsychosocial factors. AIM: To better understand the psychological and
      behavioral aspects of ED and compare the attitudes of ED patients in different
      countries. METHODS: The Cross-National Survey on Male Health Issues surveyed men
      aged 20-75 years in six countries. Participants completed questionnaires on
      attitudes, behavior, doctor-related issues, and comorbidities. MAIN OUTCOME
      MEASURES: Men rated their attitudes using a scale of 1 (strongly disagree) to 5
      (strongly agree). Responses of "somewhat agree" and "strongly agree" were
      combined and the percentage calculated for each country and overall. A mean score
      for all responses (1-5) was calculated for each country. RESULTS: Attitudes held
      by men with ED overlap significantly when compared between countries. Men in all
      countries agreed that ED was a source of great sadness for themselves and their
      partners, and nearly all disagreed with the idea that they were too old for sex.
      Men in all countries agreed that it was important to know they had the capacity
      to perform sexually, and half of all men reported they would do "nearly anything"
      to cure their ED. Men in all countries also agreed that their doctor was the best
      source of information on sexual issues. Men in the United States and the United
      Kingdom were less willing to accept ED, more motivated to find a cure, and less
      likely to consider ED a result of psychological problems. CONCLUSIONS: Attitudes
      of men with ED overlap significantly when compared between countries, but
      interesting differences were seen. Additional research is needed to understand
      how attitudes and behaviors reported reflect actual experiences. This study
      highlights some of the barriers that exist between physician-patient
      communication surrounding identification and treatment of ED.

PMID- 16422871
TI  - Relationships between erectile dysfunction, depression, and anxiety in Japanese
      subjects.
AB  - AIMS: This study aimed to elucidate the relationships between erectile
      dysfunction (ED) and depression or anxiety. METHODS: Subjects were 1,419 Japanese
      men aged 40-64 years. ED was assessed by the International Index of Erectile
      Function 5 (IIEF-5) score (Japanese version), and depression and anxiety symptoms
      were assessed by the Hospital Anxiety and Depression Scale (HADS). In this study
      ED cases were defined as those whose IIEF-5 value was less than 12, and a score
      of 8 or higher was used to classify a subject as suffering from depression or
      anxiety, respectively. The prevalence odds ratio (OR) of ED was calculated with
      confidence interval (CI) estimated by the Woolf's method by five age groups (40
      44, 45-49, 50-54, 55-59, 60-64 years). To control for age, body mass index,
      smoking, and alcohol drinking factors, we conducted the multivariate logistic
      regression analysis for calculating adjusted ORs and 99% CIs. RESULTS: ED was
      significantly associated with depression in age groups 45-49 (OR 3.42, 99% CI
      1.51-7.76) and 50-54 years (OR 2.43, 99% CI 1.11-5.35). After using multivariate
      analysis, adjusted OR also showed statistical significance. (OR 2.02, 99% CI 1.32
      3.08). ED was significantly associated with anxiety in the 50-55-year-old age
      group (OR 2.48, 99% CI 1.12-5.47). After using multivariate analysis, adjusted OR
      also showed statistical significance (OR 1.77, 99% CI 1.15-2.72). The concomitant
      depression and anxiety group (A+D+) had significantly higher prevalence of ED
      than the control group (A-D-) in both the 45-49 and 50-54 age groups. (P < 0.01)
      CONCLUSION: ED associated significantly with depression and anxiety status only
      in late 40s to early 50s (45-55 years) in male Japanese. Furthermore,
      comorbidities of depression and anxiety strengthen this association. Our results
      might be useful in furthering understanding of ED etiology and determining a
      target population for prevention in ED subjects.

PMID- 16422873
TI  - Hemodynamic effects of sildenafil citrate and isosorbide mononitrate in men with
      coronary artery disease and erectile dysfunction.
AB  - INTRODUCTION: Mild hemodynamic effects have been reported with sildenafil citrate
      therapy. AIM: To compare the hemodynamic effects of sildenafil and isosorbide
      mononitrate (ISMN) in men with coronary artery disease and erectile dysfunction.
      METHODS: A total of 31 men aged 35 years or older with coronary artery disease
      (at least 50% narrowing of the left main stem or at least 70% narrowing of any
      other coronary artery) and erectile dysfunction (receiving medication for
      erectile dysfunction or scoring less than 26 out of a maximum score of 30 on the
      erectile function domain questions of International Index of Erectile Function)
      were randomized to sildenafil 100 mg (n = 10), ISMN 40 mg (n = 11), or placebo (n
      = 10) in this single-dose multicenter study. MAIN OUTCOME MEASURES: Hemodynamic
      parameters were measured at baseline, 1, 2, 4, and 6 hours post dose. RESULTS:
      Compared with baseline, cardiac index increased slightly with sildenafil (0.29
      L/min/m2 at 1 hour) and decreased slightly with placebo (-0.12 L/min/m2 at 4
      hours) and ISMN (-0.14 L/min/m2 at 1 hour). The stroke volume index increased
      from baseline at each time point post dose with sildenafil (4.4 mL/m2 at 2
      hours), but decreased with ISMN (-5.8 mL/m2 at 1 hour) and placebo (-2.8 mL/m2 at
      4 hours). ISMN reduced mean arterial pressure more than sildenafil did (-22 vs. 
      10 mm Hg at 2 hours, respectively). Both sildenafil and ISMN increased heart rate
      (4 vs. 7 beats/minute at 1 hour, respectively) and decreased systemic vascular
      resistance, but sildenafil produced greater reductions in pulmonary vascular
      resistance. There were no serious adverse events in the sildenafil group.
      CONCLUSIONS: Sildenafil 100 mg was well tolerated and induced smaller changes in
      central and peripheral hemodynamic pressures compared with ISMN 40 mg. Moreover,
      sildenafil selectively reduced pulmonary resistance, which may have clinical
      importance in pulmonary hypertension.

PMID- 16422874
TI  - Comparison of efficacy, safety, and tolerability of on-demand tadalafil and daily
      dosed tadalafil for the treatment of erectile dysfunction.
AB  - OBJECTIVE: To assess and compare the efficacy of on-demand tadalafil and daily
      tadalafil in the treatment of erectile dysfunction. MATERIALS AND METHODS: A
      total of 145 men with a mean age of 57.3 years (range 19-82 years) and mild to
      severe erectile dysfunction of various etiologies were randomized to receive on
      demand tadalafil (20 mg) or daily tadalafil (10 mg) taken without food or alcohol
      restrictions in a trial lasting 26 weeks. The three primary outcome measures were
      changes from baseline in the erectile function domain of the International Index
      of Erectile Function (IIEF), the proportion of "yes" responses to questions 2 and
      3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included
      a Global Assessment Question administered at completion of the study. RESULTS:
      Compared with baseline, on-demand and daily tadalafil enhanced all efficacy
      outcomes. Patients receiving on-demand tadalafil (20 mg) and daily tadalafil (10
      mg) experienced a significant mean improvement of 8.3 and 11.9, respectively, in
      the erectile function domain of the IIEF from baseline (P < 0.001). The mean
      change from baseline was significantly higher for daily dosed tadalafil than for
      on-demand tadalafil (P < 0.05). Sexual intercourse was successfully completed
      (SEP3) in 69% and 84% of patients taking on-demand tadalafil and daily tadalafil,
      respectively, compared with 30% at baseline (P < 0.001). Successful completion of
      sexual intercourse was statistically higher for daily tadalafil than for on
      demand tadalafil (P < 0.05). Treatment with on-demand tadalafil or daily
      tadalafil was well tolerated, and headaches, facial flushing, and dyspepsia were
      the most frequently observed adverse events. CONCLUSION: Tadalafil was effective
      and well tolerated in this patient population. Treatment with daily tadalafil was
      associated with a significantly higher IIEF erectile function domain score and
      completion of successful intercourse compared with on-demand tadalafil.

PMID- 16422875
TI  - Use of a visual analog scale to assess pain of injection with intracavernous
      injection therapy.
AB  - AIM: Fear of pain with intracavernosal injection (ICI) therapy may discourage its
      use in patients with erectile dysfunction (ED). METHODS: We prospectively
      analyzed patient self-report of discomfort with ICI therapy for ED utilizing a
      visual analog scale from 0 to 10. RESULTS: Patient self-report using a visual
      analog scale revealed minimal discomfort, with 59 consecutive patients reporting
      an average pain score of 1.93 +/- 1.76. There was no statistical difference
      between self-administered or nurse-administered injections. The volume of the
      injection also had no statistical effect on pain score, and there was no
      difference observed between those who received alprostadil alone or combination
      treatment. Patients with diabetes mellitus did have significantly higher pain
      scores than other patients (3.31 +/- 2.25 vs. 1.62 +/- 1.39, P = 0.009), even
      when controlling for other factors. CONCLUSION: Clinicians should be aware of the
      greater potential for discomfort in ED patients with diabetes. In the majority of
      ED patients, however, discomfort is minimal, and this information should be
      helpful in alleviating fear of injection in those who may benefit from this
      therapy.

PMID- 16422876
TI  - The hemodynamics of erectile dysfunction following external beam radiation for
      prostate cancer.
AB  - INTRODUCTION: Radiation to the pelvis is associated with erectile dysfunction
      (ED). The mechanisms include neural injury, vascular alterations, and corporal
      smooth structural changes. There exists little data on the vascular assessment of
      men who present with ED following radiation therapy for prostate cancer. This
      study was conducted to evaluate the erectile hemodynamics in such a patient
      population. METHODS: Men who presented for the evaluation of ED following
      radiation therapy for prostate cancer underwent vascular evaluation in the form
      of dynamic infusion cavernosometry and cavernosography (DICC). Established
      parameters were recorded to define arterial insufficiency and venocclusive
      function including cavernosal artery occlusion pressure, flow-to-maintain, and
      pressure decay. RESULTS: Sixteen men with a mean age of 61 years presenting with
      ED after radiation underwent DICC at a mean duration post radiation of 11 months.
      All of the patients in whom arterial hemodynamics were measurable had abnormal
      arterial parameters, and 85% had abnormal venocclusive parameters. Of the
      patients who could undergo cavernosography, 80% had venous leak, most commonly
      from the crura. CONCLUSIONS: Men presenting with ED following radiation therapy
      for prostate cancer are likely to have significant alterations in erectile
      hemodynamics, often of a combined arterio-venogenic nature. In patients with
      venous leak the majority had venocclusive dysfunction with venous leak emanating
      from the crura.

PMID- 16422877
TI  - Association between the bothersomeness of lower urinary tract symptoms and the
      prevalence of erectile dysfunction.
AB  - OBJECTIVE: To assess the association between the bothersomeness of lower urinary
      tract symptoms (LUTS) and the prevalence of erectile dysfunction (ED). METHODS:
      The target population comprised all men born in 1924, 1934, or 1944 and residing
      in Tampere or 11 surrounding municipalities in Finland in 1999. A questionnaire
      was sent in May 1999 to 2,864 men, and 2,133 (75%) responded. Of them, 417 were
      excluded because of missing data on erectile function, or because they had
      prostate cancer or radical prostatectomy, leaving a total of 1,716 (60%)
      qualified respondents. LUTS was assessed by the Danish Prostatic Symptom Score,
      and ED by a short form of the International Index of Erectile Function. Logistic
      regression model was used in the multivariate analysis. RESULTS: Adjusted odds
      ratios (ORs) of ED were 2.6 (95% CI 1.3-5.2) for men with LUTS total scores of 11
      19 compared with men without LUTS and were not bothered by them, and 4.4 (2.1
      8.9) for those with scores 20 or more. Bother scores 1-3 and 4-6 were
      significantly associated with ED (OR 1.8, 95% CI 1.2-2.6 and 2.1, 1.4-3.4,
      respectively), while similar symptoms scores were not. Adjusted ORs of ED was 4.1
      (2.0-8.2) for men with a symptoms score of 10 or more compared with those free
      from symptoms, and same (OR 4.2, 95% CI 2.7-6.7) for men with similar bother
      score. Among symptoms, nocturia (adjusted OR 1.5), weak stream (OR 1.5), stress
      incontinence (OR 2.1), and overflow incontinence (OR 1.8) were significantly
      associated with ED, whereas among bother, only overflow incontinence (OR 2.2) was
      significantly correlated with ED. CONCLUSIONS: ED is a common problem in men with
      LUTS and is strongly associated with both the severity of symptoms and their
      bothersomeness. However, bother of mild LUTS affects ED more than the mild
      symptoms, emphasizing the potential of psychological mechanisms of ED.

PMID- 16422878
TI  - The prevalence of bother, acceptance, and need for help in men with erectile
      dysfunction.
AB  - INTRODUCTION: Apart from knowledge on the prevalence of erectile dysfunction
      (ED), for clinical reasons it is important to obtain information on concern or
      bother and need for help. However, information is lacking on men with ED who need
      help but do not seek medical attention. Thus, this study aimed to assess the
      distribution of bother, acceptance, and need for help in men with ED, and assess
      characteristics of patients with ED in need for help but not receiving medical
      attention for ED. METHODS: A total of 5,721 men aged 18 years and older and
      registered in 12 general practices in the middle of the Netherlands were sent a
      questionnaire by mail about sexual problems, ED, need for help, and medical
      attention. Out of 2,117 questionnaires that were returned, 1,481 were completed
      on ED, bother, and need for help. RESULTS: The prevalence of ED (according to
      World Health Organization definition) in the 1,481 men was 14.2%. Of these men
      67.3% were bothered, 68.7% did not accept ED, and 85.3% wanted help.
      Surprisingly, 41.9% of men who denied a need for help were bothered and 19.4% did
      not accept ED. Only 10.4% of men with ED received any medical care. Bother in men
      with ED was related to increasing age (decreasing above 60 years). Compared with
      men who already received help for ED, men who wanted help but did not receive it
      more often suffered from diabetes, neurological problems, and various
      cardiovascular problems. On the other hand, history of myocardial infarction
      increased the chance of getting adequate medical attention for ED. CONCLUSIONS:
      The majority of men with ED are concerned or bothered and perceive a need for
      help. Most of them do not receive any medical attention. These men are
      characterized by chronic medical conditions, visiting the physician's office
      regularly for their medical condition.

PMID- 16422881
TI  - The silver lining of a crisis: the Journal of Sexual Medicine establishes the
      ethics committee.

PMID- 16422882
TI  - Ethical aspects of sexual medicine.
AB  - INTRODUCTION: Ethics describe the ways in which moral life is understood.
      Morality comprises norms for human conduct, and addresses what is right and what
      is wrong. AIM: To provide a consensus-based summary of the ethical aspects of
      sexual medicine. METHODS: Over 200 multidisciplinary specialists from 60
      countries were divided into 17 consultation committees as part of a process
      organized by an international consultation on sexual medicine held in Paris, June
      28-July 1, 2003 in close alliance with several sexual medicine organizations.
      Embarking on a study on ethics in sexual medicine, 10 experts from eight
      countries assembled over a two-year period to develop this consensus-based
      summary. MAIN OUTCOME MEASURE: Although ethics are recognized as subjective,
      expert opinion was based on grading of evidence-based medical literature, in
      addition to cultural and ethical considerations. The process also involved
      extensive internal committee discussion, public presentation, and debate.
      RESULTS: Contemporary medical practitioners provide health care for patients from
      many different cultures from all around the world. Thus, it is recommended that
      all health professionals working in sexual medicine should above all be able to
      demonstrate respect, understanding, and tolerance toward the differing moral
      worldviews of their patients and colleagues, and the societies they represent. In
      sexual medicine, health professionals have an obligation to respect the autonomy
      of any individual that they treat, regardless of that individual's religious or
      socio-cultural tradition, race, gender, or sexual orientation. Sexual rights are
      a necessary condition for sexual health. Sexual health requires a positive and
      respectful approach to sexuality and sexual relationships as well as the
      possibility of having pleasurable and safe sexual experiences, free of coercion,
      discrimination, and violence. For sexual health to be attained and maintained,
      the sexual rights of all persons must be respected, protected, and fulfilled.
      CONCLUSIONS: Additional discussion and research on ethics in sexual medicine is
      needed.

PMID- 16422883
TI  - On Swedish women's distressing sexual dysfunctions: some concomitant conditions
      and life satisfaction.
AB  - OBJECTIVES: To explore the associations between women's distressing sexual
      dysfunctions and different aspects of life satisfaction together with women's
      concomitant socio-psychological characteristics. Thus, this descriptive article
      does not discuss causalities. METHODS: A nationally representative sample of
      sexually active Swedish women aged 18-65 years in a heterosexual steady partner
      relationship participated in 1996 in a combined structured
      interview/questionnaire investigation. Personal sexual distress caused by low
      sexual interest, insufficient lubrication, orgasm dysfunction, dyspareunia, and
      vaginism was classified as manifest and mild. Concomitant conditions explored
      were perceived health, stability of domestic situation, perception of male
      partner's sexual functions/dysfunctions per se, and some socio-demographic
      factors. Satisfaction with life as a whole and with 10 different domains of life
      were reported by using the LiSat-11 checklist. RESULTS: Main results were that a
      multitude of the independent variables were univariately associated with manifest
      and, to a lesser extent, mild distressing sexual dysfunctions. This was
      particularly true for satisfaction with partner relationship and for male's
      sexual dysfunctions. By performing multiple logistic regressions, the numbers
      were markedly reduced. The resulting statistical models still contained sexual
      partner's sexual dysfunctions and satisfaction with partner relationship as
      dominant covariants of most distressing sexual dysfunctions. CONCLUSIONS:
      Reported low level of satisfaction with partner relationship and male sexual
      dysfunctions per se are likely to co-occur with manifest but, to a lesser extent,
      mild distressing sexual dysfunctions in Swedish women aged 18-65 years.

PMID- 16422884
TI  - Low scores in the sexual health inventory for men questionnaire may indicate
      sexual disorders other than erectile dysfunction.
AB  - INTRODUCTION: A screening program aimed at early detection of erectile
      dysfunction, among other hidden morbidities, is offered by the medical services
      of the Israel Defense Force for career servicemen. Men apparently with erectile
      dysfunction can turn to a sexual rehabilitation specialist for consultation. AIM:
      To present our experience in sexual evaluation of men with low scores in the
      Sexual Health Inventory for Men (SHIM) questionnaire. METHODS: Men aged 25-50
      years go through a routine check-up at the Staff Periodic Examination Center. The
      SHIM questionnaire was used to characterize erectile dysfunction. Men who had
      scored low in the SHIM questionnaire were referred to a sexual consultation and
      evaluation. RESULTS: During 2001-2003, 11,914 men reported to the Staff Periodic
      Examination Center (mean age 34.8 +/- 7.1 years). Among 5,836 men who filled out
      the SHIM questionnaire (compliance of 48.9%), 1,570 (26.9%) men scored low. Of
      those men with low SHIM scores, 7.2% (114/1,570) underwent a sexual dysfunction
      evaluation. Only 50% (57/114) of the men in fact had erectile dysfunction, of
      whom 15.7% (9/57) also had premature ejaculation. In addition, 38.5% (44/114) of
      the men were found to have premature ejaculation only, and the rest (14/114,
      9.7%) had other sexual dysfunctions or lack of sexual knowledge. CONCLUSION: The
      SHIM questionnaire is a valuable tool for detecting various sexual dysfunctions
      other than erectile dysfunction. Incorporating the SHIM questionnaire in a
      routine check-up encourages men to seek consultation and treatment for sexual
      disorders. In addition, the SHIM questionnaire encourages men to seek sexual
      education and increase their awareness of issues concerning sexual health.

PMID- 16422885
TI  - Superoxide anion production in the rat penis impairs erectile function in
      diabetes: influence of in vivo extracellular superoxide dismutase gene therapy.
AB  - INTRODUCTION: Superoxide anion may contribute to erectile dysfunction (ED) in
      diabetes mellitus by reducing cavernosal nitric oxide (NO) bioavailability. The
      purpose of this study was to determine if gene transfer of extracellular
      superoxide dismutase (EC-SOD) can reduce superoxide anion formation and determine
      if this reactive oxygen species may contribute to diabetes-related ED in an
      experimental model of diabetes. METHODS: Three groups of animals were utilized:
      (1) control; (2) streptozotocin (STZ)-diabetic rats [60 mg/kg intraperitoneally
      (ip)] intracavernosally injected with AdCMVbetagal (negative control); and (3)
      STZ-rats intracavernosally injected with AdCMVEC-SOD. Two months after ip
      injection of STZ, groups 2 and 3 were transfected with the adenoviruses and 2
      days after transfection, all animals underwent cavernosal nerve stimulation (CNS)
      to assess erectile function. Confocal microscopy for superoxide anion and von
      Willebrand Factor (vWF) was performed in the STZ-diabetic rat. Superoxide anion
      production, total SOD activity, and cyclic guanosine monophosphate (cGMP) levels
      were measured in each experimental group of rats. RESULTS: Confocal microscopy
      demonstrated superoxide in smooth muscle and endothelial cells of the STZ-rat
      cavernosum and colocalized with vWF in the endothelium. Higher superoxide anion
      levels and decreased cGMP levels were found in the penis of STZ-rats at a time
      when erectile function was reduced. Two days after administration of AdCMVEC-SOD,
      superoxide anion levels were significantly lower in the penis of STZ-rats. Total
      SOD activity and cavernosal cGMP was increased in the penis of EC-SOD-transfected
      rats. STZ-rats transfected with AdCMVEC-SOD had a peak intracavernosal pressure
      (ICP) and total ICP to CNS that was similar to control rats. CONCLUSIONS: These
      data demonstrate that in vivo adenoviral gene transfer of EC-SOD can reduce
      corporal superoxide anion levels and raise cavernosal cGMP levels by increasing
      NO bioavailability thus restoring erectile function in the STZ-diabetic rat.

PMID- 16422887
TI  - Arteriogenic erectile dysfunction alters protein expression within the cavernosal
      tissue in an animal model.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent and often untreated
      condition. It may be a marker of underlying chronic illness and negatively
      impacts quality of life. Penile arterial insufficiency, frequently found in
      association with hypertension, dyslipidemia, diabetes mellitus, pelvic
      irradiation, trauma, and smoking, is the most common cause of ED. AIM: This study
      was designed to measure the effect of penile hypoperfusion-induced alteration and
      injury on erectile tissue at the cellular and protein level. METHODS: Eighteen 4
      month-old male Sprague Dawley rats were placed into three groups (n = 6): sham
      surgery, unilateral internal iliac artery ligation (UIIAL), and bilateral
      internal iliac artery ligation (BIIAL). MAIN OUTCOME MEASURE: Erectile function
      was assessed 4 weeks following arterial ligation surgery as measured by a rise in
      intracavernosal pressure induced by cavernosal nerve stimulation. Penile tissue
      alterations were characterized by immunohistochemistry, protein content measured
      by western blot, and "global" protein expression profile carried out by using
      surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
      (SELDI-TOF-MS) ProteinChip technology. RESULTS: Significantly lower
      intracavernous pressures were demonstrated in animals subjected to UIIAL surgery,
      which correlated to the extent of artery ligation. The intensity and quantity of
      immunohistochemical staining for neuronal nitric oxide synthase, endothelial cell
      integrity, smooth muscle cell alpha-actin, and vascular endothelial growth factor
      (VEGF) receptor flk1 were decreased in the BIIAL group compared to sham controls.
      SELDI-TOF-MS analysis revealed changes in molecular expression of a approximately
      6,560 Da protein relative to a 7,720 Da protein (peak ratio = 1.34 +/- 0.3,
      BIIAL; 0.36 +/- 0.1 controls, P < 0.05). CONCLUSIONS: In this report, an animal
      model of vascular penile insufficiency demonstrates altered protein expression
      associated with cavernosal tissue injury and reduced erectile function. Although
      the clinical significance of these observations is currently undefined, this
      model may allow greater insight into the complex biologic changes associated with
      arteriogenic ED in man.

PMID- 16422888
TI  - Long-term effect of inhibition of the angiotensin-converting enzyme (ACE) on
      cavernosal perfusion in men with atherosclerotic erectile dysfunction: a pilot
      study.
AB  - INTRODUCTION: Impaired perfusion of the corpora cavernosa is considered an
      important causal factor of erectile dysfunction (ED) in the aging male with
      atherosclerosis. Aim. On the basis of this notion, we hypothesized that
      inhibition of angiotensin-converting enzyme (ACE) may have a structural
      beneficial effect on cavernosal perfusion and subsequently on erectile function
      in men with impaired cavernosal perfusion. METHODS: A total of 59 men with
      atherosclerotic ED (mean age, 60.0 +/- 6.8 years) and impaired cavernosal
      perfusion, as demonstrated with penile-pharmaco duplex ultrasonography, were
      randomized between an ACE inhibitor and placebo treatment arm. The minimum period
      of intervention was 26 weeks (26-46 weeks). The goal of the study was to
      demonstrate an improvement of (i) cavernosal arterial perfusion demonstrated by a
      decrease of blood flow velocity waveform; and (ii) erectile function in the
      erection domain of the International Index of Erectile Function. RESULTS:
      Cavernosal perfusion improved significantly (paired samples t-test, P < 0.05) in
      both study arms, but the improvement did not differ significantly (anova, P >
      0.05) between both arms. The number of sexually active men increased, and the
      severity of ED decreased in both groups. CONCLUSION: Although a persisting
      improvement of cavernosal perfusion by at least a 6 month-administration of an
      ACE inhibitor in men with advanced atherosclerotic ED could not be demonstrated
      in this pilot study, the beneficial effect on cavernosal perfusion, sexual
      activity, and erectile function in all participants of this study is remarkable.
      This pilot study warrants a follow-up study in sexually more active men with ED
      and less advanced atherosclerosis to show that ACE inhibition may result in
      persisting improvement of cavernosal perfusion.

PMID- 16422889
TI  - Comparison of the steady-state pharmacokinetics, metabolism, and variability of a
      transdermal testosterone patch versus a transdermal testosterone gel in
      hypogonadal men.
AB  - AIM: To compare the pharmacokinetics (PK), metabolism, intra- and inter-subject
      variability of a permeation-enhanced testosterone patch versus a topical
      testosterone gel. METHODS: 28 hypogonadal men were treated with a testosterone
      patch (5 mg/day applied at 2200 h) and a 1% testosterone gel (5 g/day applied at
      0800 h; nominal delivery 5 mg/day), each for 14 days, in an open-label crossover
      design. PK profiles of total testosterone (TT) and calculated free testosterone
      (cFT) were measured on day 7 and day 14 of each treatment, with patches or gel
      applied to the abdomen; dihydrotestosterone (DHT) and estradiol (E2) profiles
      were measured on day 14. The time-average (Cavg), maximum (Cmax), time of maximum
      (Tmax) and minimum concentrations (Cmin) were derived from each profile. The
      intra- and inter-subject coefficients of variation (CVintra and CVinter) of the
      TT and cFT parameters were computed by ANOVA. RESULTS: Nightly applications of
      the patch produced a mean TT profile that mimicked the circadian pattern of
      healthy men. Morning applications of the gel produced a flatter mean profile;
      though individual subjects exhibited significant peaks at variable times. For TT,
      the mean and 90% confidence intervals of the patch/gel ratio of Cavg (1.030;
      0.936-1.133; P > 0.05) and Cmax (1.086; 0.974-1.211; P > 0.05) met the criteria
      for bioequivalence. Cmin was lower for the patch. DHT levels and DHT/T ratios
      were 2 to 3-fold higher for the gel (P < 0.0001). E2 levels and E2/T ratios were
      comparable. CVintra and CVinter for Tmax approached 100% for the gel and were 23%
      and 42%, respectively, for the patch (P < 0.0001). Other variability parameters
      were generally comparable. Both products were well tolerated, and the patches
      adhered well. CONCLUSIONS: These findings reflect the different mechanisms of
      transdermal absorption from the patch and gel and provide new considerations for
      selecting testosterone replacement therapies in hypogonadal men.

PMID- 16422890
TI  - Transfer of transdermally applied testosterone to clothing: a comparison of a
      testosterone patch versus a testosterone gel.
AB  - AIM: To assess the amount of testosterone transferred from the abdominal
      application sites of a transdermal testosterone patch and a transdermal
      testosterone gel to cotton T-shirts worn for 24 hours during each treatment.
      METHODS: During a crossover study comparing the pharmacokinetics of a
      testosterone patch versus a testosterone gel in 28 hypogonadal men, subjects wore
      fresh cotton T-shirts for 24 hours on the seventh and fourteenth days of each
      treatment and during a 24-hour baseline period. At the end of each evaluation,
      the abdominal section of the shirt was carefully cut out, extracted in alcohol,
      and analyzed for testosterone by a direct radioimmunoassay. The minimum
      quantifiable amount of testosterone was 0.03 microg per T-shirt sample. RESULTS:
      The median amounts of extracted testosterone were 0.44 microg for the baseline
      samples, 25.4 microg for the average of the two patch samples, and 6,762.7 microg
      for the average of the two gel samples (all comparisons P < 0.0001). Significant
      correlations were observed between the day 7 and day 14 data for both the patch
      (R = 0.4982; P < 0.01) and the gel (R = 0.8383; P < 0.0001). No significant
      correlations were found between the baseline, patch, or gel data, or between
      these and any demographic or pharmacokinetic parameters. A quantitative
      interpretation of the findings suggests that the baseline results are consistent
      with the transfer of testosterone in sweat; the patch results are probably due to
      the transfer of a small amount of residual testosterone left on the abdominal
      skin from the prior day's patches; and the gel results reflect the desquamation
      of stratum corneum containing a portion of the abdominally applied testosterone.
      CONCLUSIONS: There are large differences in the amount of testosterone that can
      be transferred from the application sites of transdermal patches and gels. The
      latter should be covered with clothing to minimize transfer through intimate skin
      to-skin contact.

PMID- 16422891
TI  - Prostatic specific antigen in patients with hypogonadism: effect of testosterone
      replacement.
AB  - INTRODUCTION: The effect of parenteral testosterone replacement therapy on
      prostatic specific antigen (PSA) level or the development or growth of prostate
      cancer is unclear. AIM: To assess the effect of testosterone replacement on PSA
      level in patients with hypogonadism associated with erectile dysfunction (ED).
      METHODS: A total of 187 male patients above the age of 45 with hypogonadism
      associated with ED were enrolled in this study. Patients were screened for ED by
      the erectile function domain of the International Index of Erectile Function
      (IIEF). Patients underwent routine laboratory investigations, plus total
      testosterone, and PSA assessment. Replacement treatment with parenteral
      testosterone every 2-4 weeks for 1 year was instituted. Total testosterone and
      PSA serum levels were assessed every 3 months during the treatment course.
      RESULTS: Mean age +/- SD was 62.8 +/- 11.4. Of the patients 87.7% were sexually
      active. Of the patients 10.2% had mild, 40.6% had moderate and 49.2% had severe
      ED. Of the study population, 62.5% had ED complaints for less than 5 years and
      84.5% had gradual onset of their complaint. The majority of the patients (91.4%)
      had either progressive or stationary course while the minority reported
      regressive course and improvement of the condition. There was a significant
      increase of the post-treatment testosterone level in comparison to pretreatment
      level (P < 0.05). No significant increase in the post-treatment PSA level in
      comparison to pretreatment (P > 0.05). No significant difference between pre- and
      post-treatment categories of PSA level (normal, borderline, high) in relation to
      the severity of ED (P > 0.05). There was no significant association between PSA
      level and the duration of testosterone replacement therapy in the study
      population (P > 0.05). CONCLUSION: The current study demonstrated that the level
      of PSA was not significantly changed after 1 year of testosterone replacement
      therapy in patients with hypogonadism associated with ED.

PMID- 16422892
TI  - Erectile dysfunction following surgical correction of Peyronie's disease and a
      pilot study of the use of sildenafil citrate rehabilitation for postoperative
      erectile dysfunction.
AB  - INTRODUCTION: Peyronie's disease (PD) is correctable by several surgical
      approaches including plaque incision with grafting. While the best choice of
      graft material remains controversial, the risk of postoperative erectile
      dysfunction (ED) is apparent across previous reports. AIM: We attempt to provide
      guidelines as to which patients may be at increased risk for developing
      postoperative ED after this procedure, as well as examine the role of sildenafil
      citrate (SC) in the postoperative period for prevention of this complication.
      MATERIALS AND METHODS: A retrospective review was performed on 37 patients who
      underwent surgical correction of PD with pericardial grafting after plaque
      incision. Mean follow-up was 24 months. We evaluated patient age, duration of
      disease, defect size, plaque location, degree of curvature, shaft narrowing,
      preoperative coital activity, vascular risk factors for ED, as well as
      preoperative erection grade and duplex ultrasound parameters. Twenty-six of these
      patients underwent a postoperative rehabilitation protocol of SC to enhance
      recovery of unassisted erections. RESULTS: Overall, 11 patients (29%) noted
      diminished postoperative rigidity, that compromised unassisted coitus, compared
      to preoperative status. Comparison of rates of ED among those with or without
      vascular risk factors yielded no statistically significant results. Peyronie's
      disease duration, patient age, defect size, plaque location, degree of curvature,
      and narrowing were also insignificant predictors of which patients developed ED.
      An increased percentage of patients who developed ED were not sexually active
      preoperatively compared to those that did not develop ED (58% vs. 80%). When
      patients were compared based on preoperative erection grade, those patients with
      compromised erectile function were more likely to develop postoperative ED vs.
      those with full erections (P < 0.05). No significant differences were found in
      preoperative duplex ultrasound parameters between both sets of patients. For
      those undergoing SC rehabilitation, 7 out of 26 (26%) developed ED in comparison
      to 4 out of 11 patients (36%) developing diminished rigidity when not subjected
      to the protocol. CONCLUSIONS: No single parameter was found that predicted the
      occurrence of postoperative ED with the exception of preoperative erectile
      status. The surgeon must carefully assess and consult each patient when
      considering grafting as well as consider the possible role of SC in attempting to
      prevent this complication.

PMID- 16422893
TI  - Intracavernosal irrigation by cold saline as a simple method of treating
      iatrogenic prolonged erection.
AB  - AIMS AND METHODS: The aim of this study was to evaluate the efficacy of
      aspiration and irrigation of the corpora cavernosa with cold saline as a simple
      outpatient method for treating prolonged penile erection after intracavernous
      injection of vasoactive agents. RESULTS: Aspiration and irrigation was needed in
      70 out of 122 cases with iatrogenic priapism in whom cooling of the penis and
      perineum failed to achieve detumescence. According to the temperature of the
      saline used, patients were randomized into four different groups: A, B, C, and D
      with a saline temperature 10, 15, 20, and 37 degrees C, respectively. MAIN
      OUTCOME: We used a significantly larger volume of saline in groups C and D
      compared to group A. On the other hand there was no significant difference in the
      volume of saline used between groups A and B. Complete detumescence was achieved
      in 24/25 (96%) of cases in group A compared to 9/15 (60%) of cases in group D.
      CONCLUSION: We recommend corporal aspiration and irrigation with 10 degrees C
      saline for patients with prolonged penile erection who failed to respond to the
      noninvasive measures using ice-cold compresses and physical exercise.

PMID- 16422894
TI  - Serum antioxidant enzymes and malondialdehyde levels in patients with premature
      ejaculation before and after pharmacotherapy.
AB  - BACKGROUND: In our previous study, significantly higher antioxidant enzymes and
      malondialdehyde (MDA) levels in patients with premature ejaculation (PE) compared
      to healthy controls were found. In the present study, we planned to evaluate
      antioxidant enzymes and MDA levels of patients with PE before and after
      citalopram treatment. METHODS: The study comprised 30 patients with PE according
      to Diagnostic and Statistical Manual of Mental Disorders Fourth Version (DSM-IV)
      and 30 healthy controls. The patients were randomly assigned to two groups.
      Fifteen of them (group I) received 8 weeks of citalopram treatment but the
      remaining (group II) did not. The subjects were asked to determine the average
      intravaginal ejaculation latency time (IVELT). The fasting antioxidant enzymes
      and MDA levels were measured at baseline and after 8 weeks. RESULTS: No
      statistically significant difference in the mean IVELT between groups at baseline
      was found. IVELT considerably elevated after 8 weeks of citalopram treatment in
      group I with a mean of 209 +/- 72.1 seconds but not in group II. Antioxidant
      enzymes and MDA levels did not differ between groups at baseline. At the
      evaluation of week 8, SOD, GSH-Px, and MDA levels significantly reduced during
      treatment in group I patients. CONCLUSION: In conclusion, the results suggest
      that the ability for antioxidant enzymes and MDA to normalize through symptom
      alleviation reveals that they might be trait marker of PE. Further placebo
      controlled studies are needed.

PMID- 16422895
TI  - Construction of neoglans penis: a new sculpturing technique from rectus abdominis
      myofascial flap.
AB  - INTRODUCTION: Construction of a neoglans penis may be required following glans
      amputation at circumcision, strangulation by a hair coil, or self-mutilation,
      among other indications. It may also be combined with phalloplasty to imitate the
      natural appearance and to support a penile prosthesis. AIM: This is a report on a
      novel technique of neoglans construction for a patient with an amputated glans
      penis as a result of circumcision injury. METHODS: A rectus abdominis myofascial
      flap was used. The flap was designed to be a 12 x 4 cm segment of the
      infraumbilical portion of the muscle, based on the inferior epigastric vessels.
      The flap was harvested through a paramedian incision. The penis was partially
      degloved through a circumferential incision 1 cm below its summit. The distal
      penile skin was utilized to elongate the urethra, so that the urethral meatus
      would be at the tip of the neoglans. The flap was reflected and tunneled
      underneath the mons veneris and alongside the penis, to emerge distal to the
      summit of the penis. The flap was fashioned into the shape of a glans and secured
      in place around the neourethra. The impression of a corona was achieved by
      tucking the proximal edge of the flap to its undersurface. RESULT: Six months
      following surgery, the patient had a neoglans penis, a corona, and a urethral
      meatus at the very tip. The neoglans had similar consistency, color, and shape to
      the normal glans. CONCLUSION: Construction of a neoglans penis is possible using
      the described sculpturing techniques, with satisfactory cosmetic results.

PMID- 16422896
TI  - Early experience with the American Medical Systems new tactile pump: results of a
      multicenter study.
AB  - INTRODUCTION: A new Tactile Pump for the American Medical Systems (AMS) 700
      Inflatable Penile Prosthesis (IPP) had been developed in an effort to improve
      usability for the patient. Aim. To assess the ease of use of the new Tactile
      Pump. METHODS: A prospective, multicenter study was conducted at four
      investigative sites. Preoperatively, patients completed an evaluation of the new
      Tactile Pump vs. the current design 700 pump placed in scrotal models. Patients
      compared the ease of inflation and deflation of each model. All patients were
      implanted with the AMS 700 IPP including the new Tactile Pump. Patients returned
      at 6 weeks for activation of the device and for follow-up evaluation at 3 and 6
      months. MAIN OUTCOME MEASURES: Preoperatively patients compared ease of use of
      the Tactile Pump vs. the current design. Postoperatively both physicians and
      patients assessed device functionality for inflation and deflation, ease of use
      of the pump, and time required to learn device operation. RESULTS: Thirty
      patients were implanted with the AMS 700 IPP and Tactile Pump. Thirty patients
      completed an activation visit, 20 patients completed the 3-month evaluation, and
      9 patients completed the 6-month evaluation. The average age was 62.1 years.
      Primary erectile dysfunction etiologies included organic, nonspecific 10 (33.3%),
      vasculogenic 6 (20.0%), prostatectomy 6 (20.0%), diabetes mellitus 4 (13.3%),
      Peyronie's disease 3 (10.0%), and spinal cord injury 1 (3.3%). Preoperatively
      93.3% (P < 0.001) of patients favored the Tactile Pump over the current pump on
      locating and working the inflation mechanism in the scrotal model. Patients also
      found the Tactile Pump deflation mechanism easier to find 100% (P < 0.001) and
      deflate 96.7% (P < 0.001). Most patients (86.7%) were trained to use their
      devices within 3 minutes. CONCLUSIONS: The AMS Tactile Pump provides benefit to
      patients and physicians by improving ease of use and training over the current
      IPP 700 pump.

PMID- 16422897
TI  - Adrian Walton Zorgniotti (1925-1994): renaissance urologist.
AB  - Adrian Zorgniotti was born on March 3, 1925 and died on July 6, 1994. During his
      47 years as a physician, he brought innovation and imagination to the field of
      Urology, especially in the field of erectile dysfunction (ED). Biographical
      information was obtained from Dr. Zorgniotti's curriculum vitae, his published
      articles, and his eulogies. Several of his colleagues and peers were also
      interviewed by telephone. In addition, personal experiences of this author, from
      the 9 years we spent as associates, and of several other friends were recounted.
      Dr. Zorgniotti's involvement with the history of Urology began in 1970 when he
      published his first historical treatise on Rome's first doctor, Arcagathus. He
      continued his involvement when he served as moderator for the History Forum of
      the American Urological Association (AUA) from 1975 to 1988 and as Historian for
      the AUA from 1979 to 1988. This innovator brought vision to the field of ED when
      he introduced the combination of papaverine and phentolamine as an intracavernous
      injection for the treatment of ED. He also organized the first International
      Conference on Corpus Cavernolum Revascularization in 1978 at New York University
      and published long-term results with this therapy. Adrian Zorgniotti will
      probably be best remembered by the multitude of Urologists whose lives he has
      touched for his generosity of spirit and for his ability to help shape our
      careers with a kind gesture, suggestion, or phone call. I am proud to call him a
      mentor, a colleague, and a friend.

PMID- 16422898
TI  - Abnormal testosterone levels in partners of patients using testosterone gels.

PMID- 16422901
TI  - Clinical biologic pathophysiologies of women's sexual dysfunction.
AB  - INTRODUCTION: Data concerning the biologic pathophysiology of desire, arousal,
      and orgasm in women are limited. AIM: To gain knowledge of biologic
      pathophysiology of female sexual function. METHODS. To provide state-of-the-art
      knowledge concerning female sexual dysfunction, representing the opinions of
      seven experts from five countries developed in a consensus process over a 2-year
      period. MAIN OUTCOME MEASURE: An International Consultation in alliance with key
      urological and sexual medicine societies convened over 200 multidisciplinary
      specialists from 60 countries into 17 consultation committees. The aims, goals
      and intentions of each committee were defined. Expert opinion was based on
      grading of evidence-based medical literature, extensive internal committee
      dialogue, open presentation, and debate. RESULTS: Three critical physiologic
      requirements, including intact sex steroids, autonomic/somatic nerves, and
      arterial inflow/perfusion pressure to women's genital organs play fundamental
      roles in maintaining women's sexual function. Despite this, there are nominal
      data supporting a direct pathophysiologic involvement of abnormal sex steroid
      values, and/or damage/injury to neurologic and/or blood flow integrity in women
      with problems in sexual desire, arousal, and/or orgasm. This summary details the
      available literature concerning hormonal, neurologic, and vascular organic
      pathophysiologies of women's sexual dysfunctions. CONCLUSIONS: Additional
      research on clinical pathophysiologies in women's sexual dysfunction is needed.
      This chapter encompasses data presented at the 2nd International Consultation on
      Sexual Medicine in Paris, France, June 28-July 1, 2003.

PMID- 16422902
TI  - Pathophysiology of erectile dysfunction.
AB  - INTRODUCTION: Multiple regulatory systems are involved in normal erectile
      function. Disruption of psychological, neurological, hormonal, vascular, and
      cavernosal factors, individually, or in combination, can induced erectile
      dysfunction (ED). The contribution of neurogenic, vascular, and cavernosal
      factors was thoroughly reviewed by our committee, while psychological and
      hormonal factors contributing to ED were evaluated by other committees. AIM: To
      provide state of the art knowledge on the physiology of ED. METHODS: An
      international consultation in collaboration with the major urology and sexual
      medicine associations assembled over 200 multidisciplinary experts from 60
      countries into 17 committees. Committee members established specific objectives
      and scopes for various male and female sexual medicine topics. The
      recommendations concerning state-of-the-art knowledge in the respective sexual
      medicine topic represent the opinion of experts from five different continents
      developed in a process over a 2-year period. Concerning the pathophysiology of ED
      committee, there were seven experts from five different countries. MAIN OUTCOME
      MEASURE: Expert opinion was based on the grading of evidence-based medical
      literature, widespread internal committee discussion, public presentation, and
      debate. RESULTS: The epidemiology and classification of neurogenic ED was
      reviewed. The evidence for the association between vascular ED and
      atherosclerosis/hypercholesterolemia, hypertension and diabetes was evaluated. In
      addition, the pathophysiological mechanisms implicated in vascular ED were
      defined, including: arterial remodeling, increased vasoconstriction, impaired
      neurogenic vasodilatation, and impaired endothelium-dependent vasodilatation. The
      possible mechanisms underlying the association between chronic renal failure and
      ED were also evaluated as well as the evidence supporting the association of ED
      with various classes of medications. CONCLUSIONS: A better understanding of how
      diseases interfere with the physiological mechanisms that regulate penile
      erection has been achieved over the last few years, which helps establish a
      strategy for the prevention and treatment of ED.

PMID- 16422903
TI  - Erectile dysfunction is a marker for cardiovascular disease: results of the
      minority health institute expert advisory panel.
AB  - INTRODUCTION: Cardiovascular disease and its related comorbidities are associated
      with significant morbidity and mortality and affect a disproportionately large
      number of African Americans and Hispanics. The prevalence of cardiovascular
      disease is increasing worldwide, which underscores the urgency to improve methods
      of prevention and early detection. AIM: To develop a risk assessment and
      management algorithm for primary care patients with erectile dysfunction (ED)
      that facilitates diagnosis, early intervention, and prevention of cardiovascular
      disease. METHODS: The Minority Health Institute (MHI) convened an Expert Advisory
      Panel of cardiologists and urologists to design a new practice model algorithm
      that uses ED as a clinical tool for early identification of men with systemic
      vascular disease. A draft of the algorithm was presented at a national symposium
      and comments from symposium participants were considered in the development of
      the final algorithm. MAIN OUTCOME MEASURES AND RESULTS: Erectile dysfunction is
      common and has long been considered a secondary complication of cardiovascular
      disease, diabetes, hypertension, and dyslipidemia. However, a growing body of
      evidence challenges this view, suggesting instead that ED is an early
      manifestation of atherosclerosis and a precursor to systemic vascular disease.
      Endothelial dysfunction is the etiologic factor linking ED and cardiovascular
      disease. CONCLUSIONS: The recognition of ED as an early sign of systemic
      cardiovascular disease offers an opportunity for prevention, particularly in high
      risk and underserved minority populations. The MHI algorithm stipulates that all
      men 25 years old and older regardless of sexual dysfunction complaints should be
      asked about ED. The presence of ED should prompt an aggressive assessment for
      cardiovascular risk and occult systemic vascular disease.

PMID- 16422908
TI  - The labial photoplethysmograph: a new instrument for assessing genital
      hemodynamic changes in women.
AB  - AIM: The labial photoplethysmograph (LP), a new measure for assessing genital
      responses in women, was compared to the vaginal photoplethysmograph (VP).
      METHODS: Fifteen women wore both devices simultaneously while viewing neutral,
      sexual, sexually-threatening, and threatening film clips. RESULTS: The LP and VP
      exhibited comparable specificity to sexual stimuli. Additionally, the LP
      demonstrated greater resistance to movement artifacts and a slightly higher
      correspondence with subjective measures of sexual arousal. CONCLUSION: The LP,
      while somewhat more difficult to place and less comfortable than the VP, is a
      promising new measure of genital response in women that warrants further
      development.

PMID- 16422909
TI  - Development and validation of a five-factor sexual satisfaction and distress
      scale for women: the Sexual Satisfaction Scale for Women (SSS-W).
AB  - INTRODUCTION: This article presents data based on the responses of over 800 women
      who contributed to the development of the Sexual Satisfaction Scale for Women
      (SSS-W). AIM: The aim of this study was to develop a comprehensive, multifaceted,
      valid, and reliable self-report measure of women's sexual satisfaction and
      distress. METHODS: Phase I involved the initial selection of items based on past
      literature and on interviews of women diagnosed with sexual dysfunction and an
      exploratory factor analysis. Phase II involved an additional administration of
      the questionnaire, factor analyses, and refinement of the questionnaire items.
      Phase III involved administration of the final questionnaire to a sample of women
      with clinically diagnosed sexual dysfunction and controls. RESULTS: Psychometric
      evaluation of the SSS-W conducted in a sample of women meeting DSM-IV-TR criteria
      for female sexual dysfunction and in a control sample provided preliminary
      evidence of reliability and validity. The ability of the SSS-W to discriminate
      between sexually functional and dysfunctional women was demonstrated for each of
      the SSS-W domain scores and total score. CONCLUSION: The SSS-W is a brief, 30
      item measure of sexual satisfaction and sexual distress, composed of five domains
      supported by factor analyses: contentment, communication, compatibility,
      relational concern, and personal concern. It exhibits sound psychometric
      properties and has a demonstrated ability to discriminate between clinical and
      nonclinical samples.

PMID- 16422907
TI  - A nitric oxide-releasing PDE5 inhibitor relaxes human corpus cavernosum in the
      absence of endogenous nitric oxide.
AB  - INTRODUCTION: In conditions with severe deficiency of endogenous nitric oxide
      (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase
      type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile
      dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic
      approach in such cases. AIM: We therefore aimed to compare sildenafil and NO
      releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence
      or presence of endogenous NO. METHODS: The two compounds were compared in
      reducing the phenylephrine-induced tone of human corpus cavernosum in the
      presence or absence of an inhibitor of NO synthase (L-NAME; 500 microM) or an
      inhibitor of soluble guanylate cyclase (ODQ, 10 microM). RESULTS: NCX-911 was as
      potent as sildenafil in control conditions (EC(50) = 733.1 +/- 94.4 nM and 800.7
      +/- 155.8 nM, respectively). The potency of NCX-911 was not altered but that of
      sildenafil decreased significantly in the presence of L-NAME (EC(50) = 980.4 +/-
      106.7 nM and 2446.7 +/- 256.8 nM, respectively; P < 0.001 for sildenafil vs.
      control). Both compounds below 1 microM failed to induce relaxation in the
      presence of ODQ (EC(50) = 6,578 +/- 1150 nM and 6,488 +/- 938 nM for NCX-911 and
      sildenafil, respectively). CONCLUSION: These results show that the potency of NCX
      911 was maintained unlike sildenafil in the absence of endogenous NO confirming
      the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions.

PMID- 16422910
TI  - Scale for Quality of Sexual Function (QSF) as an outcome measure for both
      genders?
AB  - BACKGROUND: For years, there has been interest in sexual dysfunction and its
      impact on quality of life but usually focused on one gender. Therapeutic options
      that became available raised the interest to evaluate effects on the other
      partner but there is no standardized instrument applicable for both genders. This
      paper reports first data regarding the development of a new general "Quality of
      Sexual Function" (QSF) scale. METHODS: The raw scale was based on our own gender
      specific scales and the pertinent literature. The scale was applied in over 700
      persons of a cross-sectional survey in Germany. Factorial analyses were performed
      to describe the internal structure (domains) of the scale and for item reduction.
      Internal consistency reliability and some aspects of validity were analyzed with
      the same community sample preliminary reference values determined. RESULTS: The
      scale consists of 32 specific items and eight general questions. Four dimensions
      were identified: "psycho-somatic quality of life,""sexual activity,""sexual
      (dys)function-self-reflection," and "sexual (dys)function-partner's view." The
      internal consistency reliability coefficients of the total scale and the
      subscales were good as were the total-domain correlations. Content validity was
      promising. CONCLUSION: This self-administrable 40-item QSF scale can measure and
      compare quality of sexual function for both genders. The scale was well accepted
      by the respondents. It is easy to answer and the evaluation is simple. Only a few
      results of reliability and validity have been established in this early stage of
      the development of the new instrument. Further research is needed to complete
      many missing aspects of reliability and the construct validity, particular its
      sensitivity to treatment effects.

PMID- 16422911
TI  - Incidence of metabolic syndrome and insulin resistance in a population with
      organic erectile dysfunction.
AB  - INTRODUCTION: Advanced age in men is accompanied by an increased prevalence of
      cardiovascular disease (CVD) and erectile dysfunction (ED). Prior studies
      revealed that 56% of an ED population have asymptomatic myocardial ischemia, 75%
      of men with CAD have symptoms of ED, and 91% of our ED patients have
      cardiovascular risks. AIM: Because metabolic syndrome (MS) and insulin resistance
      (IR) are both predictors of CVD, we wished to evaluate these parameters in our
      population. METHODS: Our men (N = 154) were evaluated for multiple cardiovascular
      risk factors and graded on severity of ED. The severity of ED was evaluated by
      the Sexual Health Inventory for Men (SHIM) questionnaire. The prevalence of MS
      was determined by NCEP/ATP III criteria. Insulin resistance was measured by
      QUICKI. MAIN OUTCOME MEASURES: Bivariate associations among total
      cholesterol/high-density lipoprotein (HDL), triglyceride/HDL, and Quantitative
      Insulin Sensitivity Check Index (QUICKI) were compared. Chi-square analysis was
      used to evaluate the relation between the presence and severity of IR with the
      severity of ED. RESULTS: The total cholesterol/HDL ratio was moderately and
      negatively correlated with QUICKI (r = -0.33; P < 0.01) and similarly for the
      triglyceride/HDL ratio (r = -0.32; P < 0.01). Metabolic syndrome was present in
      43% of our ED population as opposed to 24% in a matched patient population.
      Approximately 79.2% of our total population had IR and 73.3% of the nondiabetic
      portion (N = 120) had IR, compared to 26% in a general population study.
      Metabolic syndrome (P = 0.01), IR (P = 0.01), and fasting blood sugar (FBS) >110
      mg/dL (P = 0.01) correlated positively and moderately with increasing severity of
      ED by SHIM score. CONCLUSION: Men with ED have a high incidence of MS and IR.
      Early detection of metabolic disease in patients with ED may be a gateway to the
      reduction endothelial dysfunction in younger men with increased cardiovascular
      risk but who present for treatment of ED alone.

PMID- 16422912
TI  - Sildenafil citrate response correlates with the nature and the severity of penile
      vascular insufficiency.
AB  - INTRODUCTION: Sildenafil citrate is a highly effective erectogenic agent.
      However, predicting which patients will respond to this agent is often difficult.
      While the patient response to this agent is dependent on the nitric oxide
      guanylate cyclase-cyclic guanosine monophosphate cascade, the integrity of penile
      arterial flow and venocclusive mechanism is also important. Duplex Doppler penile
      ultrasonography can reliably document penile hemodynamics. This study aimed at
      defining response rates based on degree of penile vascular sufficiency. METHODS:
      This study enrolled patients who met strict criteria for sildenafil citrate
      response who had also undergone penile ultrasound. Correlation was drawn between
      the nature and the severity of the vascular insufficiency and the response rate
      to sildenafil citrate. RESULTS: The distribution of vascular diagnoses was
      arteriogenic 64%, venogenic 6%, mixed vascular insufficiency 18%, and normal 12%.
      The best response was seen in those men with normal vascular studies, 80%
      responding. Fifty-three percent of all men with any abnormality on penile
      ultrasound responded; 65% of men with arteriogenic erectile dysfunction (ED), 25%
      of patients with venogenic ED, and 6% of men with a mixed vascular insufficiency
      were responders. There was a correlation between the degree of vascular
      impairment and the response rate. All men with venogenic ED who responded had
      mild leak. CONCLUSION: These data demonstrate a correlation between the nature
      and severity of penile vascular disease and the ability to respond to sildenafil
      citrate. These data may be useful to the sexual medicine practitioner when
      counseling patients regarding oral erectogenic therapy.

PMID- 16422913
TI  - Vardenafil improves satisfaction rates, depressive symptomatology, and self
      confidence in a broad population of men with erectile dysfunction.
AB  - INTRODUCTION: Vardenafil is a potent and selective phosphodiesterase 5 (PDE5)
      inhibitor developed for the treatment of erectile dysfunction (ED). Fixed-dose
      and flexible-dose studies have previously established the efficacy and
      tolerability of vardenafil. AIM: To assess, besides the usual measures of
      efficacy, the quality of erection, satisfaction with the sexual experience,
      symptoms of depression, and overall confidence. METHODS: This 12-week double
      blind, placebo-controlled flexible-dose study assessed patients from the general
      ED population. Patients underwent a 4-week treatment-free period before
      randomization to vardenafil or matching placebo. Initial dosage was vardenafil 10
      mg for 4 weeks. At 4 weeks, patients could switch to 5 or 20 mg (or corresponding
      placebo), or remain on 10 mg for an additional 4 weeks; dose switching was also
      optional for the last 4 weeks. This paper describes per-patient success in
      satisfaction with hardness of erection, satisfaction with overall sexual
      experience, effect on overall self-confidence, and an assessment of symptoms of
      depression using the Center for Epidemiologic Studies Depression Scale. RESULTS:
      Mean per-patient satisfaction rates with erection hardness increased after
      vardenafil treatment to 43%, 59%, and 63% at weeks 4, 8, and 12, respectively,
      compared to placebo with 10%, 21%, and 23% (all P < 0.005 vs. placebo).
      Vardenafil also improved mean per-patient overall satisfaction 50-65% over the 4
      12 week study period compared with 17-28% for placebo (P < 0.005). Symptoms of
      depression were statistically significantly reduced compared to placebo (P =
      0.02); the effect was observed particularly in patients who were depressed at
      baseline (P = 0.01). Significantly more patients in the vardenafil treatment
      group reported improved self-confidence than those who received placebo (P <
      0.005). CONCLUSIONS: A flexible-dose regimen of vardenafil improved satisfaction
      rates, symptoms of depression, and self-confidence, providing patients with an
      effective ED therapy that contributes to overall improvements in sexual function
      and confidence.

PMID- 16422915
TI  - On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations
      for relevant ejaculation delay and consequent solutions.
AB  - INTRODUCTION: Recently, the idea has emerged that on-demand use of serotonin
      reuptake inhibitors (SSRIs), particularly short half-life, should be equally
      effective in delaying ejaculation as daily SSRI treatment of premature
      ejaculation. AIM: To provide evidence that SSRI-induced ejaculation delay is
      mainly dependent on pharmacodynamic properties of the drug and hardly on
      pharmacokinetic factors, and that combined SSRI administration with specific 5
      hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger
      ejaculation delay than acute SSRI monoadministration. METHODS: We performed a
      detailed analysis of serotonin neurotransmission and reviewed animal studies with
      5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on
      demand SSRI treatments publications and the current debate on a definition of
      premature ejaculation. MAIN OUTCOME MEASURES: Intravaginal ejaculation latency
      time (IELT). RESULTS: Acute SSRI administration leads to only a mild or no
      increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5
      HT receptors. Existing on-demand SSRI treatment studies suffer from
      methodological insufficiencies, and the reported high-fold increases of
      ejaculation time contradict with neuropharmacological insights from serotonin
      metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor
      antagonists significantly increases the ejaculation time acutely compared to
      acute SSRI monoadministration. CONCLUSION: On-demand SSRI treatment has less
      ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half
      life are likely leading to much less ejaculation delay than current registered
      SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the
      likelihood of clinically relevant ejaculation delay after on-demand treatment. On
      demand SSRIs with short half-life that insufficiently delay ejaculation in men
      with IELTs less than 1 minute should be called ejaculation-delaying drugs rather
      than drugs against premature ejaculation.

PMID- 16422914
TI  - Intracavernous sodium nitroprusside (SNP) versus papaverine/phentolamine in
      erectile dysfunction: a comparative study of short-term efficacy and side
      effects.
AB  - OBJECTIVE: The aim of our work is to evaluate the efficacy of intracavernous
      sodium nitroprusside (SNP) in management of erectile dysfunction (ED) in a
      clinical comparative study with papaverine/phentolamine in ED patients. METHODS:
      The study included 40 patients with ED divided into two groups. Group I include
      20 patients receiving intracavernous (30 mg papaverine + 1 mg phentolamine)
      followed 1 week later by intracavernous 300 microg SNP. Group II included 20
      patients receiving the same regimen of group I but with intracavernous SNP first
      followed by papaverine/phentolamine 1 week later. All patients were assessed
      clinically for their response and any developing complications. RESULTS: The
      numbers of good and poor responders were not statistically significant (P > 0.05)
      among the two groups. The mean erectile duration of SNP was similar to bimix (P >
      0.05). No side-effects whether local or systemic occurred with SNP while priapism
      and local penile pain were recorded with bimix solution. CONCLUSIONS:
      Intracavernous pharmacotherapy is still a reliable method both for diagnosis and
      for treatment of ED. While preliminary results of our study show a potential of
      SNP to be an effective and safe intracavernous agent, long-term self-injection
      clinical trials are needed before large-scale usage is recommended.

PMID- 16422916
TI  - A surgical algorithm for men with combined Peyronie's disease and erectile
      dysfunction: functional and satisfaction outcomes.
AB  - INTRODUCTION: Men with Peyronie's disease who also have erectile dysfunction
      represent a challenge to the urologist. Historically, penile prosthesis surgery
      has been the management strategy of choice for this population. This study was
      undertaken to define the outcomes of a penile reconstructive surgery algorithm in
      men with Peyronie's disease and concomitant erectile dysfunction (ED). METHODS:
      Patients presenting with combined Peyronie's disease and erectile dysfunction
      were treated with vasoactive therapy initially. All patients underwent dynamic
      infusion cavernosometry and cavernosography. Nonresponders to erectogenic
      pharmacotherapy were advised to undergo penile prosthetic surgery. Responders to
      erectogenic therapy were considered candidates for either corporoplasty or plaque
      incision and grafting. The International Index of Erectile Function (IIEF)
      questionnaire was used to compare erectile function and satisfaction profiles
      serially pre- and postoperatively between the patients in the three groups.
      RESULTS: Sixty-two patients constituted the study population. Eighty-one percent
      of the patients responded to erectogenic pharmacotherapy. Postoperative IIEF
      erectile function domain scores were statistically higher for implant patients
      and lower for plaque incision and grafting patients compared to preoperative
      scores. Postoperative IIEF satisfaction domain scores were higher for
      corporoplasty and implant patients and lower for plaque incision and grafting
      patients compared to preoperative scores. CONCLUSIONS: The surgical algorithm
      used in this study leads to excellent IIEF erectile function and satisfaction
      scores for corporoplasty and implant patients; however, plaque incision and
      grafting patients had poor functional and satisfaction outcomes. These data
      support the concept that not all men with combined ED and Peyronie's disease
      require penile prosthetic surgery, and furthermore, plaque incision and grafting
      surgery is a poor option for men with combined disease.

PMID- 16422917
TI  - Nikolaj A. Bogoraz (1874-1952): pioneer of phalloplasty and penile implant
      surgery.
AB  - Phalloplasty and penile implants are outstanding pioneering procedures introduced
      in 1936 by the Russian surgeon Nikolaj A. Bogoraz and are thus of eminent
      interest to the urological and plastic surgeon. This article from the history of
      medicine will discuss his biography and scientific achievements during the first
      half of the 20th century.

PMID- 16422918
TI  - A broken intracavernous needle: successful ultrasound-guided removal.
AB  - INTRODUCTION: Common complications of intracavernous injection therapy include
      pain, hematoma formation, syncope, prolonged erections, and penile fibrosis. Rare
      reported complications include postinjection cavernositis, intracorporeal needle
      breakage. AIM: We report a case of postinjection intracavernous needle breakage
      with successful ultrasound-guided retrieval. METHODS: A 32-year-old patient
      complaining of a 6-month penile pain following intracavernous papaverine
      injection presented to our department. Clinical examination and penile ultrasound
      revealed a broken intracavernous needle at the left mid-dorsum aspect of the
      penis with surrounding fibrosis. A decision was made to remove the broken needle.
      RESULTS: The needle was dislodged effortlessly under local anesthesia.
      CONCLUSION: A deeply seated intracavernous broken needle should be immediately
      retrieved. Patients must be carefully instructed on the proper injection
      technique with emphasis on the delicacy of the needle and the possibility of
      needle breakage during injection.

PMID- 16422919
TI  - Retained rear-tip extenders in redo penile prosthesis surgery: a case for
      heightened suspicion and thorough physical examination.
AB  - INTRODUCTION: Penile Prosthesis infection is a dreaded complication that can
      occur after primary inflatable penile implants. Redo prosthesis operations and
      salvage procedures have become increasingly popular after these inflections.
      These operations, however, have higher rates of re-infection as compared to
      primary implants. AIM: We describe a patient who was referred for repeat redo
      penile prosthesis surgery in whom retained rear-tip extenders harboring purulent
      fluid was discovered during physical examination. RESULTS: The patient underwent
      exploration and two rear-tip extenders were removed. He later underwent redo
      prosthesis insertion and the device remains fully functional and infection free
      at follow-up. CONCLUSION: This case conveys the importance of a thorough physical
      examination and raises the index of suspicion for retained prosthesis fragments
      in patients with recurrent penile prosthesis infections.

PMID- 16422921
TI  - Abstracts from the 11th World Congress of the International Society for Sexual
      and Impotence Research.

PMID- 16422954
TI  - Physiology of female sexual function: animal models.
AB  - INTRODUCTION: Data concerning the physiology of desire, arousal, and orgasm in
      women are limited because of ethical constraints. Aim. To gain knowledge of
      physiology of female sexual function through animal models. METHODS: To provide
      state-of-the-art knowledge concerning female sexual function in animal models,
      representing the opinions of seven experts from five countries developed in a
      consensus process over a 2-year period. MAIN OUTCOME MEASURE: Expert opinion was
      based on the grading of evidence-based medical literature, widespread internal
      committee discussion, public presentation, and debate. RESULTS: Sexual desire may
      be considered as the presence of desire for, and fantasy about, sexual activity.
      Desire in animals can be inferred from certain appetitive behaviors that occur
      during copulation and from certain unconditioned copulatory measures. Proceptive
      behaviors are dependent in part on estrogen, progesterone, and drugs that bind to
      D1 dopamine receptors, adrenergic receptors, oxytocin receptors, opioid
      receptors, or gamma-amino butyric acid receptors. Peripheral arousal states are
      dependent on regulation of genital smooth muscle tone. Multiple
      neurotransmitters/mediators are involved including adrenergic, and nonadrenergic,
      noncholinergic agents such as vasoactive intestinal polypeptide, nitric oxide,
      neuropeptide Y, calcitonin gene-related peptide, and substance P. Sex steroid
      hormones, estrogens and androgens, are critical for structure and function of
      genital tissues including modulation of genital blood flow, lubrication,
      neurotransmitter function, smooth muscle contractility, mucification, and sex
      steroid receptor expression in genital tissues. Orgasm may be investigated by
      urethrogenital (UG) reflex, in which genital stimulation results in rhythmic
      contractions of striated perineal muscles and contractions of vagina, anus, and
      uterine smooth muscle. The UG reflex is generated by a multisegmental spinal
      pattern generator involving the coordination of sympathetic, parasympathetic, and
      somatic efferents innervating the genital organs. Serotonin and dopamine may
      modulate UG reflex activity. CONCLUSIONS: More research is needed in animal
      models in the physiology of female sexual function.

PMID- 16422955
TI  - Physiology of erectile function.
AB  - INTRODUCTION: There are numerous investigations concerning the balance and
      interactions between relaxant and contractile factors regulating penile smooth
      muscle (arterial and trabecular) tone, the determinant of penile flaccidity or
      erection. Enhanced knowledge of erectile physiology may improve management of men
      with erectile dysfunction. Aim. To provide state-of-the-art knowledge on the
      physiology of erectile function. METHODS: An international consultation in
      collaboration with the major urology and sexual medicine associations assembled
      over 200 multidisciplinary experts from 60 countries into 17 committees.
      Committee members established specific objectives and scopes for various male and
      female sexual medicine topics. The recommendations concerning state-of-the-art
      knowledge in the respective sexual medicine topic represent the opinion of
      experts from five continents developed in a process over a two-year period.
      Concerning the physiology of erectile function and pathophysiology of erectile
      dysfunction committee, there were seven experts from five countries. MAIN OUTCOME
      MEASURE: Expert opinion was based on the grading of evidence-based medical
      literature, widespread internal committee discussion, public presentation, and
      debate. RESULTS: Key roles in the mechanism determining the tone of penile smooth
      muscle are played by the rise of the intracellular concentration of free calcium
      and the sensitivity of the contractile machinery to calcium, endothelial health,
      endothelium-derived nitric oxide, endothelium-derived hyperpolarizing factor
      (EDHF), neuronal nitric oxide, cyclic guanosine monophosphate-dependent protein
      kinase and phosphodiesterase type 5. CONCLUSIONS: A number of new mechanisms have
      been identified for the local regulation of penile smooth muscle contractility
      and therefore penile erection. Molecules participating in these pathways can be
      considered targets for the development of new treatments to treat erectile
      dysfunction.

PMID- 16422956
TI  - Psychophysiological assessment in premenopausal sexual arousal disorder.
AB  - INTRODUCTION: Female sexual arousal disorder (FSAD) is a complex diagnostic
      category whose definition continues to evolve. AIM: The purpose of this study was
      to explore the physiological patterns of genital arousal in 31 women with and 30
      women without sexual arousal difficulties using a vaginal photoplethysmograph. In
      addition, subtypes of FSAD, based on a recently proposed redefinition, were
      explored on measures of sexual arousal. RESULTS: Whereas there were no
      psychophysiological or subjective sexual arousal differences when the entire
      group of women with arousal complaints was compared to a control group,
      significant differences emerged when subtypes of arousal disorder were compared.
      Only women fitting the description of "Genital Arousal Disorder" showed evidence
      of impaired psychophysiological arousal, whereas those characterized with
      "Subjective Sexual Arousal Disorder" and "Combined Genital and Subjective Sexual
      Arousal Disorder" did not differ from the control group. These subgroups also
      differed in the correlation between psychophysiological and subjective arousal.
      CONCLUSION: Overall, there is evidence for diagnostic heterogeneity in FSAD which
      supports the recent redefinition of this disorder into subtypes.

PMID- 16422957
TI  - A Swedish telephone help-line for sexual problems: a 5-year survey.
AB  - INTRODUCTION: Telephone help-lines for people with sexual problems have been
      established in many European countries during the late decade. They, however,
      have very different modes of operation, and very few reports focusing on the way
      they function have been published internationally. AIM: To describe the methods
      and activities of a Swedish help-line for sexual problems. METHODS: In the 5
      years, from 1999 to 2003, 27,387 persons called the Swedish toll-free help-line
      for "impotence and sexual problems" that operates around the clock. The majority
      of callers appeared to be looking for information on erectile dysfunction. A
      counseling option staffed by experts in sexual medicine counseled 2,817 (men 73%,
      women 27%). A further 478 callers were professionals wanting information or
      advice. RESULTS: Among a wide spectrum of problems associated with the callers'
      sexual life, sexual dysfunctions were the most frequent. Calls about sexual
      abuse, sexual preference, paraphilias, and other subjects were also received.
      Among those with sexual dysfunction, 33% of men and 41% of women had more than
      one sexual dysfunction. These were often concomitant with a frequently drug
      treated, medical condition. In addition to counseling, the majority of callers
      were advised to contact physicians or specialists in sexology/sexual medicine for
      further help. CONCLUSION: Competent person-to-person telephone counseling in the
      multifaceted bio-psycho-social field of sexual problems requires broad knowledge
      on sexual medicine.

PMID- 16422958
TI  - Prevalence of erectile dysfunction among young adults: results of a large-scale
      survey.
AB  - INTRODUCTION: Erectile dysfunction (ED) can be an early and first sign of an
      underlying systemic disease. A screening program is offered by the Medical
      services of the Israel Defense Force for career servicemen at the Staff Periodic
      Examination Center (SPEC) aimed at early detection of morbidity. The Sexual Human
      Inventory for Males (SHIM) questionnaire was introduced to these men in order to
      identify ED, to offer men with ED suitable treatment options, and to investigate
      underlying systemic diseases. AIM: To provide epidemiological data regarding the
      prevalence of ED among a large-scale young adult population. METHODS: Subjects
      aged 25-50 years are undergoing a routine check-up at SPEC. Blood samples,
      physiological measures, demographic variables, information on health status and
      smoking habits are recorded and documented. The SHIM self-administrated
      questionnaire was used to characterize ED. RESULTS: During 2001-2003, 11,914
      males reported to SPEC (average age 34.8 +/- 7.1 years). Five thousand eight
      hundred thirty-six of them chose to answer the SHIM questionnaire (compliance of
      48.9%). According to the SHIM scores, at least one out of three men (26.9%)
      suffered from ED (19%, 7%, and 1% had mild, moderate, and severe ED,
      respectively). ED was prevalent also among young adults: 22.1% of males under-40
      had low SHIM scores (<21). Severity of ED correlated with age and diabetes
      mellitus. CONCLUSION: In light of these results, we conclude that ED is a major
      health concern among young men as well. Incorporating questions regarding sexual
      health in a routine check-up may encourage more men to seek treatment, not only
      for ED, but also for underlying diseases.

PMID- 16422959
TI  - Efficacy and safety of daily tadalafil in men with erectile dysfunction
      previously unresponsive to on-demand tadalafil.
AB  - OBJECTIVE: To assess the efficacy and safety of daily tadalafil, a potent
      selective phosphodiesterase 5 inhibitor, for the treatment of erectile
      dysfunction (ED) in men previously unresponsive to on-demand tadalafil. MATERIALS
      AND METHODS: A total of 112 men with a mean age of 63 (range 21-79) and moderate
      to severe ED of various aetiologies were treated with tadalafil, taken on a daily
      basis at flexible daily doses of 10 and 20 mg for 12 weeks. The three primary
      outcomes were changes from the pretreatment and on-demand tadalafil baseline in
      the erectile function domain of the International Index of Erectile Function and
      the proportion of yes responses to questions 2 and 3 of the Sexual Encounter
      Profile. Additional efficacy instruments included a Global Assessment Question
      administered at completion of the study. RESULTS: Compared with pretreatment and
      on-demand tadalafil baseline, daily dosed tadalafil significantly enhanced all
      efficacy outcome variables. Patients receiving daily tadalafil (10 mg)
      experienced a significant mean improvement of 12.8 and 8.2 in the International
      Index of Erectile Function erectile function domain score from baseline (P <
      0.001) and from on-demand tadalafil, respectively (P < 0.001). Fifty-eight
      percent of intercourse attempts (Sexual Encounter Profile question 3) were
      successfully completed (P < 0.001 vs. pretreatment baseline, P < 0.001 vs. on
      demand tadalafil). Improved erections at end point were reported by 69% of men
      compared with 42% of men with on-demand tadalafil. Daily tadalafil was well
      tolerated with headache, dyspepsia, and facial flushing as the most frequent
      adverse events. CONCLUSION: Daily tadalafil (10/20 mg) was effective and well
      tolerated in this study population and is an effective salvage for previous on
      demand tadalafil nonresponders.

PMID- 16422960
TI  - Vardenafil improves erectile function in men with erectile dysfunction
      irrespective of disease severity and disease classification.
AB  - BACKGROUND: Vardenafil (Levitra) is a potent and selective phosphodiesterase 5
      (PDE5) inhibitor used in the management of erectile dysfunction (ED). This
      retrospective subgroup analysis assessed the effectiveness of vardenafil
      treatment in men with ED of different baseline severity and disease
      classification. METHODS: Data from two pivotal, randomized, double-blind, placebo
      controlled clinical trials enrolling men from the general ED population who
      received placebo or vardenafil 5 mg, 10 mg, or 20 mg during a 12-week treatment
      period were retrospectively analysed, stratifying by psychogenic, organic, and
      mixed ED disease classification as determined by the investigator. Efficacy
      endpoints included the International Index of Erectile Function (IIEF)-Erectile
      Function (EF) domain score, per-patient diary response rates to questions on
      penile insertion [Sexual Encounter Profile (SEP-2)] and maintenance of erection
      (SEP-3) and rates of positive response to the Global Assessment Question (GAQ).
      RESULTS: Data from 1,385 men who received at least one dose of study medication
      and had pre- and post-baseline measures of efficacy available (intent-to-treat
      population) are presented. At baseline 37-41% of patients had severe ED, 30-34%
      moderate, 22% mild-to-moderate and 6-8% mild ED. At baseline, 46-51% of patients
      were considered to have an organic cause for ED, 13-16% psychogenic ED, and 36
      38% mixed classification of ED. For all classifications and for mild-to-moderate
      to severe ED, men treated with 10 or 20 mg of vardenafil showed statistically and
      clinically significant improvements (P < 0.001) in IIEF-EF scores, diary response
      rates to the SEP-2 and SEP-3 questions, and GAQ as compared with those given
      placebo. The greatest improvements relative to placebo were noted in patients
      with more severe ED. The most common treatment-emergent adverse events were
      headache, flushing, rhinitis, dyspepsia, and were dose-related, mostly mild to
      moderate in intensity and consistent with the class. CONCLUSIONS: Vardenafil
      improves EF in men with ED irrespective of investigator-determined classification
      and baseline ED severity.

PMID- 16422961
TI  - Intracavernous chlorpromazine versus phentolamine: a double-blind clinical
      comparative study.
AB  - INTRODUCTION: Intracavernous pharmacotherapy is one of the most common treatment
      modalities of erectile dysfunction (ED). There are different drugs that are used
      for intracavernous injection including papaverine, phentolamine, prostaglandins
      E1, phenoxybenzamine, and moxisylate. AIM: The aim of this study is to evaluate
      the efficacy of chlorpromazine as an intracavernous vasoactive agent alone or
      with other drugs. METHODS: This study was performed on 50 patients presenting to
      our department complaining of ED. Patients were divided into three groups
      according to the type of intracavernous drug injected. Group A included 20
      patients who received an intracavernous injection of 1 mL bimix (30 mg papaverine
      + 1 mg phentolamine) followed a week later by intracavernous test dose using a 1
      mL mixture of papaverine and chlorpromazine (30 mg papaverine + 2.5 mg
      chlorpromazine). Group B included 20 patients who received an intracavernous
      injection of 1 mL trimix (30 mg papaverine + 1 mg phentolamine + 10 microg PGE1).
      A week later they received another intracavernous test dose using a 1 mL mixture
      of papaverine, PGE1, and chlorpromazine (30 mg papaverine + 2.5 mg chlorpromazine
      + 10 microg PGE1). Group C included 10 patients who received various
      intracavernous injections of chlorpromazine in doses 1 mg, 2 mg, 5 mg, and 10 mg.
      RESULTS: There was no significant difference in erection response and erection
      duration between phentolamine and chlorpromazine. Prolonged erection occurred in
      two patients of group B and postural hypotension occurred in three patients of
      group C. CONCLUSION: Chlorpromazine can be used as an intracavernous vasoactive
      agent; it is similar to phentolamine in efficacy and short-term side effect
      profile.

PMID- 16422962
TI  - Does sildenafil enhance quality of nocturnal erections in healthy young men? A
      NPT-RigiScan study.
AB  - OBJECTIVE: To assess the effect of sildenafil on nocturnal erectile function (EF)
      in young healthy volunteers with normal sexual function (SF) according to the
      International Index of Erectile Function (IIEF) questionnaire. METHODS: Thirty
      three young (mean age 21 +/- 0.3 years; range 18-25) healthy volunteers not
      taking any medications who had normal SF and an EF domain >26 on the IIEF
      questionnaire were evaluated. Erectile function was assessed using the RigiScan
      (Dacomed Corp., MN, USA) during three nights: night 1 = adaptation to the NPT
      Rigiscan apparatus, night 2 = baseline recording of eight parameters, and night 3
      = recordings after ingestion of sildenafil 100 mg. Data on the number of
      erections, erection duration, minimal and maximal base tumescence, minimal and
      maximal tip tumescence, and base and tip rigidity were analysed using anova with
      repeated measures. RESULTS: A statistically significant improvement in all eight
      parameters was observed as a result of sildenafil administration: number of
      erections from 3.1 +/- 0.7 to 4.0 +/- 0.7 (P < 0.05), erection time 22 +/- 3.5 to
      34.2 +/- 5.9, minimal base tumescence 8.2 +/- 0.8 to 8.7 +/- 0.8, maximal base
      tumescence 12.1 +/- 0.7 to 14.2 +/- 0.7, base rigidity 75.6 +/- 3.1 to 81.6 +/-
      3.6, tip rigidity 70.6 +/- 1.5 to 75.9 +/- 3.1, minimal tip tumescence 5.9 +/-
      0.5 to 6.5 +/- 0.6, and maximal tip tumescence 8.6 +/- 0.6 to 11.7 +/- 0.7 (P <
      0.0001 for each of the last seven parameters). The mean sleep duration, 7.3 hours
      (range 6.30-9.20 hours), was similar for both nights of recording. CONCLUSIONS:
      Sildenafil increases the quality and number of nocturnal erections as tested by
      the NPT-RigiScan in young healthy volunteers with normal EF.

PMID- 16422963
TI  - Penile prosthetic surgery for Peyronie's disease: defining the need for
      intraoperative adjuvant maneuvers.
AB  - INTRODUCTION: There are a number of accepted approaches to the patient with
      Peyronie's disease and erectile dysfunction (ED), including penile prosthesis
      surgery. During prosthesis surgery for Peyronie's disease some men are left with
      residual curvature upon maximum device inflation. This analysis was undertaken to
      define how often and in which patients, intra-operative adjuvant maneuvers are
      required. METHODS: Men undergoing penile prosthesis surgery for combined
      Peyronie's disease/ED constituted the study population. Residual curvature >10
      degrees was deemed to warrant the use of a secondary maneuver to correct
      curvature. In this analysis, plaque release incisions were utilized and grafting
      was performed only if there was overt exposure of the prosthesis. RESULTS: 36 men
      were included in the analysis. All patients with preoperative curvatures <or=30
      degrees had complete resolution of the penile curvature with full inflation of
      the prosthesis alone. Of patients who had >45 degrees curvature preoperatively,
      86% needed plaque incision to achieve adequate penile straightening. Grafting was
      required in only 5.5% patients and both of these patients had preoperative
      curvature >60 degrees . CONCLUSIONS: In 61% of patients with combined Peyronie's
      disease/ED in this study, the placement of a three-piece inflatable penile
      prosthesis alone corrected the penile curvature. 86% of patients requiring plaque
      incision had preoperative curvatures >45 degrees . This information should enable
      surgeons to plan such operations more effectively and to counsel patients more
      comprehensively prior to operative intervention.

PMID- 16422964
TI  - Review of phosphodiesterases in the urogenital system: new directions for
      therapeutic intervention.
AB  - INTRODUCTION: With the success of Phosphodiesterase (PDE) type 5 inhibitors
      (i.e., sildenafil, tadalafil, vardenafil) in the treatment of erectile
      dysfunction (ED), PDEs are considered attractive targets for drug intervention in
      the urogenital tract. AIM: To review the role of PDEs, which exist as a
      superfamily of enzymes comprising 11 distinct families, in the urogenital system,
      focusing on anatomical locations, functions and dysfunctions, potential disorders
      that could be treated, and any promising new selective PDE inhibitors under
      development. METHODS: Included are (i) abstracts from 2001, 2002, and 2003; (ii)
      a MEDLINE search from 1996 through December 2003; and (iii) a pipeline search for
      therapeutics in development. Data from animal experiments are presented when
      there is a paucity of human data, but with the caveat that the distribution of
      PDE isozymes in a specific tissue can vary between species. RESULTS: PDE mRNA and
      protein have been localized throughout the normal human urogenital tract. Double
      blind, placebo-controlled studies suggest possible new clinical roles for
      sildenafil, including prophylaxis to preserve penile smooth muscle and erectile
      function after radical prostatectomy, and treatment of ejaculatory delay
      secondary to serotonergic reuptake inhibitor antidepressant therapy. Open-label
      studies suggest a potential clinical role for: vinpocetine (a PDE1 inhibitor) in
      the treatment of incontinence and low-compliance bladder; and sildenafil in the
      treatment of premature ejaculation, prostate-related lower urinary tract
      symptoms, and in women who have had unsuccessful in vitro fertilization. Several
      new orally administered PDE5 inhibitors are in early clinical development for the
      treatment of ED. Potential indications for PDE inhibitors that are suggested by
      preclinical data include Peyronie's disease, ureteral colic, male and female
      birth control, and prevention of preterm labor. CONCLUSIONS: Drug selectivity and
      differential PDE tissue distribution allow for potential targeted intervention
      for numerous disorders related to the urogenital tract.

PMID- 16422965
TI  - Possible correlation between type 1 diabetes mellitus and female sexual
      dysfunction: case report and literature review.
AB  - INTRODUCTION: Sexual dysfunction in diabetic women has received less attention in
      clinical research than the sexual symptoms of diabetic men. Although conflicting
      results have been reported, several studies suggest an increased prevalence of
      deficient vaginal lubrication in women with diabetes mellitus. As support to the
      hypothesis of a potential diabetes-related arousal dysfunction caused by a
      decrease in vaginal lubrication of women with Type 1 diabetes mellitus, we
      describe the following case report. METHODS: A 29-year-old white woman was found
      with a sexual arousal disorder of sudden onset, complicated by loss of orgasm and
      sexual desire, in absence of any marital, relational, psychological, or
      gynecological cause. RESULTS: One month later she was diagnosed with severe Type
      1 diabetes. With the correction of diabetes and without other treatment of the
      sexual dysfunction, she experienced a full recovery of her sexual complaints.
      CONCLUSIONS: The case illustrates the importance of being aware of female sexual
      dysfunction as an early symptom of diabetes mellitus and suggests that a good
      glycemic control would be fundamental to restore a normal sexual activity in
      diabetic women. It also demonstrates the need to take into account, not only in
      males, a sexual history in the management of diabetes mellitus.

PMID- 16422967
TI  - Pharmacotherapy for erectile dysfunction.
AB  - INTRODUCTION: Advances in understanding of the biochemistry and physiology of
      penile erection have led to breakthroughs in pharmacotherapy of erectile
      dysfunction. AIM: To provide recommendations/guidelines concerning state-of-the
      art knowledge for the putative molecular and cellular mechanisms of action of
      centrally and peripherally acting drugs currently utilized in pharmacotherapy of
      erectile dysfunction. METHODS: An international consultation in collaboration
      with the major urology and sexual medicine associations assembled over 200
      multidisciplinary experts from 60 countries into 17 committees. Committee members
      established specific objectives and scopes for various male and female sexual
      medicine topics. The recommendations concerning state-of-the-art knowledge in the
      respective sexual medicine topic represent the opinion of experts from five
      continents developed in a process over a two-year period. Concerning the
      Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10
      countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence
      based medical literature, widespread internal committee discussion, public
      presentation and debate. RESULTS: Selective and potent oral PDE5 inhibitors have
      significantly more affinity than cGMP and form broader molecular interactions
      with multiple amino acids, thereby blocking access to cGMP in the catalytic sites
      of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency,
      selectivity and pharmacokinetics, lead to cGMP elevation and relaxation
      facilitation of penile corpus cavernosum smooth muscle cells following sexual
      stimulation. Various centrally acting drugs influence sexual behaviour. In
      particular, the dopaminergic substance apomorphine is a central enhancer that
      acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2)
      receptor agonist, induces and increases penile erection responses via
      disinhibition, following sexual stimulation. CONCLUSIONS: There is a need for
      more research in the pharmacotherapeutic development of central and peripheral
      agents for safe and effective erectile dysfunction treatment.

PMID- 16422968
TI  - Health care cost implications of sildenafil citrate.
AB  - INTRODUCTION: As prescription drug expenditures increase, third-party payors are
      increasingly scrutinizing costs and reimbursement guidelines, such as for
      medications that treat chronic conditions that are not necessarily directly life
      threatening (i.e., obesity, nicotine addiction, and erectile dysfunction). AIM:
      To review the costs and consequences of pharmacy benefit reimbursement policies
      related to erectile dysfunction therapies, using sildenafil citrate as the case
      study. METHODS: Data and references were found through searches of PubMed and
      Google. RESULTS AND CONCLUSIONS: To meet the varied health needs of a defined
      population under reasonable resource constraints requires analysis of cost and of
      the economic and non-economic consequences of a treatment. Based on analysis of
      sildenafil data, oral therapy of erectile dysfunction provides substantial cost
      savings when compared with other treatment options and contributes insignificant
      overall costs to health plans. Regardless, health plans impose controls to limit
      reimbursement. Because erectile dysfunction is often a precursor to other
      conditions, such limitations could compromise detection and management of
      underlying disease (e.g., depressive, cardiovascular, and urogenital).
      Reimbursement restrictions may also decrease membership satisfaction and re
      enrollment rates.

PMID- 16422969
TI  - The multinational Men's Attitudes to Life Events and Sexuality (MALES) Study
      Phase II: understanding PDE5 inhibitor treatment seeking patterns, among men with
      erectile dysfunction.
AB  - OBJECTIVE: The aim of Phase II of the Men's Attitudes to Life Events and
      Sexuality (MALES) Study is to explore PDE5 inhibitor treatment seeking among men
      with erectile dysfunction (ED). METHODS: Phase II of the MALES study involved
      2,912 men, aged 20-75 years, from 8 countries (U.S., U.K., Germany, France,
      Italy, Spain, Mexico, and Brazil), who reported ED. Participants were recruited
      from the MALES Phase I sample [1] and via booster methods (e.g., physician
      referral, street interception), and completed self-report questionnaires
      concerning the characteristics of their ED, their efforts to seek PDE5 inhibitor
      treatment for their sexual dysfunction, and attitudinal and referent influences
      that potentially affect treatment-seeking. Statistical analyses focus on
      identification of correlates of PDE5 inhibitor treatment seeking. RESULTS: PDE5
      inhibitor utilization is strongly associated with ED sufferers' assessment of the
      severity of their sexual dysfunction, with their belief that medication for ED is
      dangerous, and with their perceptions of whether physicians, other professionals,
      and spouses or family members are supportive of their seeking treatment. ED
      sufferers who evaluate their sexual dysfunction as severe, who believe that
      medication for ED is not dangerous, and who perceive support for treatment
      seeking from referent others, are more likely to utilize PDE5 inhibitor
      treatment. CONCLUSION: Findings indicate that perceived ED severity, beliefs
      about ED medication, and referent influences are strongly correlated with
      utilization of PDE5 inhibitor therapy. These findings aid our understanding of
      factors that may incline men with ED to seek-or to avoid-PDE5 inhibitor therapy
      for their sexual dysfunction, and provide a basis for clinical and educational
      interventions to assist men with ED to seek appropriate treatment.

PMID- 16422970
TI  - Update on clinical trials of tadalafil demonstrates no increased risk of
      cardiovascular adverse events.
AB  - INTRODUCTION: Cardiovascular disease and erectile dysfunction (ED) share similar
      risk factors and often occur concomitantly. Therefore, men with ED may be at
      increased risk for cardiovascular adverse events. AIM: The aim of this
      retrospective analysis was to evaluate the cardiovascular adverse events in
      clinical trials of tadalafil, an effective medication for the treatment of ED.
      METHODS: An integrated analysis of cardiovascular adverse events was performed on
      a database from 35 controlled clinical trials (placebo [N = 2,118] and tadalafil
      [N = 5,228]) and eight open-label trials of tadalafil (tadalafil [N = 6,939]).
      Some patients in controlled trials also received tadalafil in the open-label
      extension phase of four trials. Across all trials, the dose range of tadalafil
      was 2-25 mg, with the majority of patients receiving tadalafil 20 mg. This
      analysis represents an update of previous published results. RESULTS: In 35
      controlled tadalafil clinical trials, the incidence of cardiovascular adverse
      events was low and comparable in tadalafil- and placebo-treated patients. The
      rate of myocardial infarction (MI) across all controlled and open-label studies
      was 0.33 per 100 patient-years in tadalafil-treated patients (N = 10,460, patient
      exposure = 5,088 patient-years). The MI rate in tadalafil-treated patients was
      comparable to that in placebo-treated patients (0.41 per 100 patient-years; N =
      2,118; 489 patient-years), and to that in an age-standardized male population
      (0.6 per 100 patient-years). The cardiac mortality rate in tadalafil-treated
      patients across all studies (N = 10,460) was 0.12 per 100 patient-years which was
      not increased compared with the cardiac mortality rate of 0.26 per 100 patient
      years reported in an age-standardized male population. CONCLUSIONS: In tadalafil
      clinical trials, the incidence of cardiovascular adverse events in patients
      receiving tadalafil was low and comparable to placebo. Tadalafil did not increase
      the rate of MI or cardiac mortality compared with reported rates from
      epidemiological studies. This favorable cardiovascular safety profile for
      tadalafil is important, because men with ED commonly have cardiovascular disease
      and may seek medical therapy for ED.

PMID- 16422971
TI  - Earliest time to onset of action leading to successful intercourse with
      vardenafil determined in an at-home setting: a randomized, double-blind, placebo
      controlled trial.
AB  - INTRODUCTION: Vardenafil, a potent and selective oral PDE5 inhibitor, is
      efficacious and generally well-tolerated in men with erectile dysfunction (ED).
      Of considerable interest to patients and physicians is an understanding of the
      time required after dosing to attain penile erection sufficient for successful
      sexual intercourse. AIM: To determine the earliest time to onset of action of
      vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in
      men with ED. METHODS: A prospective, randomized, double-blind, parallel-group, at
      home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in
      North America and Europe. Following a 4-week run-in period, patients were
      randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N =
      247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the
      elapsed time from dosing to attainment of an erection perceived to be adequate
      for penetration that led to intercourse completion. Earliest time of onset was
      defined as the fastest time among the first four doses for each patient. Time
      points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a
      backward stepping procedure. RESULTS: Mean baseline erectile function domain
      score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of
      men on vardenafil 10/20 mg had at least one erection in the first four doses
      perceived to be sufficient for penetration with subsequent intercourse completion
      compared to 26% on placebo (P < 0.0001). A statistically superior response to
      vardenafil vs. placebo was observed in these responders at all times >or= 10 and
      >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a
      retrospective analysis using time intervals of <or= 15, <or= 20, <or= 25 and <or=
      30 minutes between dosing and erection adequate for penetration, 75-77% of these
      intercourse attempts were successful (SEP3 positive) by patients receiving
      vardenafil 10/20 mg, compared to 45-47% of attempts by those who received
      placebo. Vardenafil 10/20 mg was generally well-tolerated with headache (7%/12%
      vs. 1%) and flushing (6%/9% vs. < 1%) reported more frequently than with placebo.
      No patient discontinued vardenafil therapy due to adverse events. CONCLUSION: In
      this large, at-home study, the onset of action of vardenafil with subsequent
      intercourse completion was recognized as early as 10 minutes after dosing.

PMID- 16422972
TI  - Duration of action of sildenafil citrate in men with erectile dysfunction.
AB  - INTRODUCTION: Viagra (sildenafil citrate) has a rapid onset of action for the
      treatment of erectile dysfunction (ED). However, its duration of action has not
      been thoroughly investigated. Practical knowledge of the time window available
      for sexual intercourse would be valuable for couples planning sexual activity.
      AIM: We investigated the duration of action of sildenafil in men with ED.
      METHODS: This was a double-blind, randomized, placebo-controlled, four-way
      crossover study of 16 men, mean age of 55 years (range, 36-68 years) with ED of
      no known organic cause. Participants received oral sildenafil (100 mg) or placebo
      1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included
      the duration of erections of >or= 60% rigidity, assessed by penile
      plethysmography (RigiScan), and the proportion of sildenafil responders, defined
      as patients with erections of >or= 60% rigidity for >or= 4 minutes and >or= 50%
      improvement over erections achieved in their placebo arm. Self-assessed duration
      of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was
      also recorded. RESULTS: At 1, 8, and 12 hours after dosing with sildenafil, the
      mean duration of erections with >or= 60% rigidity was 26, 11, and 8 minutes,
      respectively, compared with only 3 minutes after placebo dosing (P < 0.05).
      However, the mean duration of self-assessed erections was 33, 23, and 16 minutes,
      respectively, compared with 7 minutes after placebo dosing (P < 0.05), and was
      greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1
      hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil
      administration. CONCLUSION: Sildenafil improved objective and self-assessed
      erectile function in men with ED, and the duration of action of sildenafil was
      longer than that previously reported. These data suggest that sildenafil may be
      effective in a significant proportion of men with ED up to 12 hours after being
      taken.

PMID- 16422973
TI  - Vardenafil improves patient satisfaction with erection hardness, orgasmic
      function, and overall sexual experience, while improving quality of life in men
      with erectile dysfunction.
AB  - PURPOSE: The North American Pivotal Trial was designed to investigate the
      efficacy and safety of vardenafil in males with erectile dysfunction (ED).
      MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled,
      multicenter, fixed-dose, parallel group, 6-month study, vardenafil at three doses
      (5 mg, 10 mg, and 20 mg) was compared to placebo with the primary efficacy
      variables being the International Index of Erectile Function (IIEF) Erectile
      Function (EF) domain score and per patient diary response success rates for
      penetration and maintenance of erection through completion of intercourse.
      Additional efficacy variables included IIEF domain scores measuring intercourse
      satisfaction, orgasmic function, sexual desire, and overall satisfaction. Diary
      entries for overall per patient satisfaction rates for hardness and sexual
      experience were also measured. Improvements in quality of sexual life were
      assessed using the Fugl-Meyer quality of life (QoL) questionnaire. RESULTS:
      Compared to placebo, patients taking 10 mg and 20 mg doses of vardenafil showed
      statistically significantly greater improvement in IIEF domain scores measuring
      intercourse satisfaction (10.3 and 10.3 vs. 7.7), orgasmic function (7.1 and 6.9
      vs. 5.3), overall satisfaction. (7.1 and 7.1 vs. 5.2) for vardenafil 10 mg and 20
      mg vs. placebo, respectively, at last observation carried forward (LOCF).
      Vardenafil 5 mg was statistically significantly better than placebo for the
      secondary IIEF domain variables of intercourse satisfaction (8.9 vs. 7.7) and
      overall satisfaction (6.3 vs. 5.2) for vardenafil vs. placebo, respectively, at
      LOCF. Per patient satisfaction rates for the secondary diary variables measuring
      erection hardness (38%, 52%, 58% and 18%) and overall satisfaction (45%, 58%, 62%
      and 23%) were dose dependent and statistically significantly superior for
      vardenafil at 5 mg, 10 mg and 20 mg compared with placebo, respectively.
      Patients' answers to the Fugl-Meyer QoL questionnaire assessing improvement in
      sexual life also indicated statistically significant superiority for all doses of
      vardenafil vs. placebo treatment. The most frequent adverse events (AE) in the 5
      mg, 10 mg, and 20 mg of vardenafil and placebo groups, respectively, were:
      headache (10%, 22%, 21% and 4%), flushing (5%, 10%, 13% and 0%), dyspepsia (1%,
      4%, 6% and < 1%), and rhinitis (9%, 14%, 17% and 5%). Most AEs were mild or
      moderate in severity and transient in nature. CONCLUSION: Vardenafil was superior
      to placebo for IIEF domain scores, per patient success rates for diary questions,
      and assessment of quality of sexual life, in a broad range of patients with ED
      irrespective of etiology or severity. Vardenafil was generally well tolerated,
      with most AEs being mild or moderate in severity and transient in nature.

PMID- 16422974
TI  - Determining the earliest time within 30 minutes to erectogenic effect after
      tadalafil 10 and 20 mg: a multicenter, randomized, double-blind, placebo
      controlled, at-home study.
AB  - INTRODUCTION: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor used for the
      treatment of erectile dysfunction (ED). The minimal time to onset of erectogenic
      effect in the at-home setting has not been evaluated. AIM: The goal was to
      determine the earliest time to erectogenic effect leading to successful
      intercourse within 30 minutes after taking tadalafil 10 and 20 mg. METHODS: The
      multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase
      2 study enrolled men at least 21 years old with a minimum 3-month history of ED.
      Four single doses each of placebo, tadalafil 10 mg, or 20 mg were taken at home
      once every 8-10 days. Using a stopwatch, couples recorded in Sexual Encounter
      Profile diaries the earliest time within 30 minutes after dosing to the first
      erection adequate for vaginal penetration, and whether the erection led to
      successful intercourse. MAIN OUTCOME MEASURES: The primary analysis compared the
      percentage of erections resulting in successful intercourse between tadalafil
      groups and placebo at one-minute intervals using a step-down procedure. A
      secondary analysis compared the overall distribution of time to erectogenic
      effect between treatment groups using the Cox Regression Method. RESULTS:
      Compared to placebo, a significant erectogenic response to tadalafil 20 mg was
      found from 30 minutes down to 16 minutes after dosing (P = 0.012). Response to
      tadalafil 10 mg approached significance (P = 0.054) at 30 minutes. As analysed by
      the Cox Regression Method, a significant erectogenic response was found from 30
      minutes down to 15 minutes after dosing for tadalafil 20 mg (P = 0.020), and from
      30 minutes down to 26 minutes for tadalafil 10 mg (P = 0.042). Fifty-two percent
      of men taking tadalafil 20 mg had at least one successful intercourse attempt
      within 30 minutes compared to 35.1% of men taking placebo (P = 0.038).
      CONCLUSIONS: This stopwatch-based study demonstrated a pharmacodynamic effect
      within 30 minutes after dosing for tadalafil 10 and 20 mg.

PMID- 16422975
TI  - Efficacy and safety of on-demand oral tadalafil in the treatment of men with
      erectile dysfunction in Taiwan: a randomized, double-blind, parallel, placebo
      controlled clinical study.
AB  - INTRODUCTION: Tadalafil is a phosphodiesterase type 5 inhibitor for the treatment
      of erectile dysfunction (ED). Past clinical trials have assessed its efficacy and
      safety in western populations. Tadalafil has not been investigated in a large
      clinical trial with a South-east Asian population. AIM: To assess the efficacy
      and safety of on-demand tadalafil for the treatment of ED in a 12-week, double
      blind, placebo-controlled study in Taiwan. METHODS: Men with mild to severe ED of
      various etiologies were randomized to receive placebo, tadalafil 10 mg, or
      tadalafil 20 mg, taken as needed (maximum once daily). Efficacy assessments
      included the International Index of Erectile Function, the Sexual Encounter
      Profile (SEP) diary, and a Global Assessment Question (GAQ). RESULTS: Tadalafil
      significantly improved erectile function compared with placebo (P < 0.005, all
      measures). At endpoint, the patients receiving tadalafil reported a greater mean
      per-patient percentage of successful intercourse attempts (SEP question 3: 70.0%,
      10 mg; 78.0%, 20 mg) than placebo-treated patients (42.8%) and a greater
      proportion of improved erections (GAQ: 92.3% and 84.6% vs. 54.5%). Most treatment
      emergent adverse events were mild or moderate. The most common adverse events
      were back pain, dyspepsia, and myalgia. CONCLUSIONS: Tadalafil was an effective,
      well-tolerated therapy for men in Taiwan with ED of broad-spectrum severity and
      etiology.

PMID- 16422980
TI  - Summary of the recommendations on sexual dysfunctions in women.
AB  - INTRODUCTION: Women's sexual dysfunctions include persistent or recurrent
      disorders of sexual interest/desire, disorders of subjective and genital arousal,
      orgasm disorder, pain and difficulty with attempted or completed intercourse.
      There are limited recommendation/guideline documents pertaining to the diagnosis
      and treatment of women's sexual dysfunctions. AIM: To provide
      recommendations/guidelines concerning state-of-the-art knowledge for the clinical
      management of women's sexual dysfunctions. METHODS: An International Consultation
      in collaboration with the major sexual medicine associations assembled over 200
      multidisciplinary experts from 60 countries into 17 committees. Committee members
      established specific objectives and scopes for various sexual medicine topics.
      The recommendations concerning state-of-the-art knowledge in the respective
      sexual medicine topic represent the opinion of experts from five continents
      developed in a process over a 2-year period. Ten experts from four countries
      compiled the Recommendations on Sexual Dysfunctions in Women. MAIN OUTCOME
      MEASURE: Expert opinion was based on grading of evidence-based medical
      literature, widespread internal committee discussion, public presentation and
      debate. RESULTS: Recommendations and guidelines concerning the various sexual
      dysfunctions were updated. A comprehensive assessment of medical, sexual and
      psychosocial history is recommended for diagnosis and management planning.
      Indications for general and focused pelvic genital examination and laboratory
      testing are included. Recently revised definitions for sexual desire/interest
      disorder, arousal disorders (genital, subjective, combined and persistent),
      orgasm disorder, dyspareunia and vaginismus are presented. An evidence-based
      approach to management is provided. CONCLUSIONS: There is a need for more
      research and scientific reporting, re-assessment, and management of women's
      sexual dysfunction including long-term outcome studies.

PMID- 16422979
TI  - Summary of the recommendations on sexual dysfunctions in men.
AB  - INTRODUCTION: There are few published guidelines for the management of sexual
      dysfunctions in men and women, despite the prevalence and lack of attention to
      these problems. Disorders of sexual function in men include erectile dysfunction,
      orgasm/ejaculation disorders, priapism, and Peyronie's disease. AIM: To provide
      evidence-based and expert-opinion consensus guidelines for the clinical
      management of men's sexual dysfunctions. METHODS: An International Consultation
      in collaboration with major urological and sexual medicine societies assembled
      over 200 multidisciplinary experts from 60 countries into 17 consultation
      committees. Committee members established the scope and objectives for each
      chapter. Following intensive review of available data and publications,
      committees developed evidence-based guidelines in each area. MAIN OUTCOME
      MEASURE: New algorithms and guidelines for assessment and treatment of men's
      sexual dysfunction were developed. The Oxford system of evidence-based review was
      systematically applied. Expert opinion was based on systematic grading of the
      medical literature, in addition to cultural and ethical considerations. RESULTS:
      Recommendations and guidelines for men's sexual dysfunction are presented. These
      guidelines were developed as evidence-based, patient-centered, and
      multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a
      basic evaluation was recommended for all patients, with optional and specialized
      testing reserved for special cases. A new treatment algorithm is proposed. This
      algorithm provides a clinically relevant guideline for managing ED in the large
      majority of men. New treatment guidelines and algorithms are provided for men's
      orgasm and ejaculation disorders, including premature ejaculation, retrograde and
      delayed ejaculation. Finally, expert opinion-based guidelines for the clinical
      management of priapism and Peyronie's disease are provided. CONCLUSIONS:
      Additional research is needed to validate and extend these guidelines.
      Nonetheless, this summary encompasses the recommendations concerning men's sexual
      dysfunctions presented at the 2nd International Consultation on Sexual Medicine
      in Paris, France, June 28-July 1, 2003.

PMID- 16422981
TI  - Epidemiology/risk factors of sexual dysfunction.
AB  - INTRODUCTION: Accurate estimates of prevalence/incidence are important in
      understanding the true burden of male and female sexual dysfunction and in
      identifying risk factors for prevention efforts. AIM: To provide
      recommendations/guidelines concerning state-of-the-art knowledge for the
      epidemiology/risk factors of sexual dysfunctions in men and women. METHODS: An
      International Consultation in collaboration with the major urology and sexual
      medicine associations assembled over 200 multidisciplinary experts from 60
      countries into 17 committees. Committee members established specific objectives
      and scopes for various male and female sexual medicine topics. The
      recommendations concerning state-of-the-art knowledge in the respective sexual
      medicine topic represent the opinion of experts from five continents developed in
      a process over a 2-year period. Concerning the Epidemiology/Risk Factors
      Committee, there were seven experts from four countries. MAIN OUTCOME MEASURE:
      Expert opinion was based on grading of evidence-based medical literature,
      widespread internal committee discussion, public presentation and debate.
      RESULTS: Standard definitions of male and female sexual dysfunctions are needed.
      The incidence rate for erectile dysfunction is 25-30 cases per thousand person
      years and increases with age. There are no parallel data for women's sexual
      dysfunctions. The prevalence of sexual dysfunction increases as men and women
      age; about 40-45% of adult women and 20-30% of adult men have at least one
      manifest sexual dysfunction. Common risk factor categories associated with sexual
      dysfunction exist for men and women including: individual general health status,
      diabetes mellitus, cardiovascular disease, other genitourinary disease,
      psychiatric/psychological disorders, other chronic diseases, and socio
      demographic conditions. Endothelial dysfunction is a condition present in many
      cases of erectile dysfunction and there are common etiological pathways for other
      vascular disease states. Increasing physical activity lowers incidence of ED in
      males who initiate follow-up in their middle ages. CONCLUSIONS: There is a need
      for more epidemiologic research in male and female sexual dysfunction.

PMID- 16422982
TI  - Revised definitions of women's sexual dysfunction.
AB  - INTRODUCTION: Existing definitions of women's sexual disorders are based mainly
      on genitally focused events in a linear sequence model (desire, arousal and
      orgasm). AIM: To revise definitions based on an alternative model reflecting
      women's reasons/incentives for sexual activity beyond any initial awareness of
      sexual desire. METHODS: An International Definitions Committee of 13 experts from
      seven countries repeatedly communicated, proposed new definitions and presented
      at the 2nd International Consultation on Sexual Medicine in Paris July 2003. MAIN
      OUTCOME MEASURE: Expert opinions/recommendations are based on a process that
      involved review of evidence-based medical literature, extensive internal
      committee discussion, informal testing and re-testing of drafted definitions in
      various clinical settings, public presentation and deliberation. RESULTS: Women
      have many reasons/incentives for sexual activity. Desire may be experienced once
      sexual stimuli have triggered arousal. Arousal and desire co-occur and reinforce
      each other. Women's subjective arousal may be minimally influenced by genital
      congestion. An absence of desire any time during the sexual experience designates
      disorder. Arousal disorder subtypes are proposed that separate an absence of
      subjective arousal from all types of sexual stimulation, from an absence of
      subjective arousal when the only stimulus is genital. A new arousal disorder has
      provisionally been suggested, namely that of persistent genital arousal. Orgasm
      disorder is limited to absence of orgasm despite high subjective arousal.
      Dyspareunia includes partial painful vaginal entry attempts as well as pain with
      intercourse. Variable reflex muscle tightening around the vagina and an absence
      of abnormal physical findings are noted in the definition of vaginismus. Women's
      sexuality is highly contextual and descriptors are recommended re past
      psychosexual development, current context, as well as medical status. Diagnosing
      sexual disorders need not imply intrinsic dysfunction of the woman's own sex
      response system. CONCLUSIONS: The International Definitions Committee has
      recommended a number of fundamental changes to the existing definitions of
      women's sexual disorders.

PMID- 16422983
TI  - Clinical evaluation and management strategy for sexual dysfunction in men and
      women.
AB  - INTRODUCTION: The optimal approach for identification and evaluation of the
      sexual problems in men and women in primary care or general medicine practice has
      not been consensed. AIM: To provide recommendations/guidelines concerning state
      of-the-art knowledge for clinical evaluation and management strategies in the
      evaluation and treatment of sexual dysfunction in men and women, emphasizing
      evidence-based medicine and a patient-centered framework. METHODS: An
      International Consultation in collaboration with the major urology and sexual
      medicine associations assembled over 200 multidisciplinary experts from 60
      countries into 17 committees. Committee members established specific objectives
      and scopes for various male and female sexual medicine topics. The
      recommendations concerning state-of-the-art knowledge in the respective sexual
      medicine topic represent the opinion of experts from five continents developed in
      a process over a 2-year period. Concerning the Clinical Evaluation and Management
      Strategies Committee, there were 12 experts from five countries. MAIN OUTCOME
      MEASURE: Expert opinion was based on grading of evidence-based medical
      literature, widespread internal committee discussion, public presentation and
      debate. RESULTS: Three concepts underlie sexual medicine management: (i) adoption
      of a patient-centered framework for evaluation and treatment; (ii) application of
      the principles of evidence-based medicine in diagnostic and treatment planning;
      and (iii) use of a unified management approach in men and women. When taken
      together, these three principles provide a balanced and integrated approach to
      sexual dysfunction management. Common algorithms for diagnosis and management of
      men and women with sexual dysfunction, brief sexual symptom checklists, basics in
      history and physical examination, indications for specialized referral and
      development of a follow-up strategy are presented. CONCLUSIONS: More research is
      needed in understanding the role of evidence-based and patient-centered medicine
      in the clinical evaluation and management strategies of men and women with sexual
      dysfunction.

PMID- 16422984
TI  - Disorders of orgasm and ejaculation in men.
AB  - INTRODUCTION: Ejaculatory/orgasmic disorders, common male sexual dysfunctions,
      include premature ejaculation, inhibited ejaculation, anejaculation, retrograde
      ejaculation and anorgasmia. AIM: To provide recommendations/guidelines concerning
      state-of-the-art knowledge for management of ejaculation/orgasmic disorders in
      men. METHODS: An International Consultation in collaboration with the major
      urology and sexual medicine associations assembled over 200 multidisciplinary
      experts from 60 countries into 17 committees. Committee members established
      specific objectives and scopes for various male and female sexual medicine
      topics. The recommendations concerning state-of-the-art knowledge in the
      respective sexual medicine topic represent the opinion of experts from five
      continents developed in a process over a 2-year period. Concerning the Disorders
      of Ejaculation/Orgasm in Men Committee, there were nine experts from six
      countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence
      based medical literature, widespread internal committee discussion, public
      presentation and debate. RESULTS: Premature ejaculation management is dependent
      upon etiology. When secondary to ED, etiology-specific treatment is employed.
      When lifelong, initial pharmacotherapy (SSRI, topical anesthesia, PDE5
      inhibitors) is appropriate. When associated with psychogenic/relationship
      factors, behavioral therapy is indicated. When acquired, pharmacotherapy and/or
      behavioral therapies are preferred. Retrograde ejaculation, diagnosed with
      spermatozoa and fructose in centrifuged post-ejaculatory voided urine, is managed
      by education, patient reassurance, pharmacotherapy or bladder neck
      reconstruction. Men with anejaculation or anorgasmia have a biologic failure of
      emission and/or psychogenic inhibited ejaculation. Men with age-related penile
      hypoanesthesia should be educated, reassured and be instructed in revised sexual
      techniques which maximize arousal. CONCLUSIONS: More research is needed in
      understanding management of men with ejaculation/orgasmic dysfunction.

PMID- 16422985
TI  - Disorders of orgasm in women.
AB  - INTRODUCTION: Orgasm is a sensation of intense pleasure creating an altered
      consciousness state accompanied by pelvic striated circumvaginal musculature and
      uterine/anal contractions and myotonia that resolves sexually-induced
      vasocongestion and induces well-being/contentment. In 1,749 randomly-sampled U.S.
      women, 24% reported an orgasmic dysfunction. AIM: To provide
      recommendations/guidelines concerning state-of-the-art knowledge for management
      of orgasmic disorders in women. METHODS: An International Consultation in
      collaboration with the major urology and sexual medicine associations assembled
      over 200 multidisciplinary experts from 60 countries into 17 committees.
      Committee members established specific objectives and scopes for various male and
      female sexual medicine topics. The recommendations concerning state-of-the-art
      knowledge in the respective sexual medicine topic represent the opinion of
      experts from five continents developed in a process over a 2-year period.
      Concerning the Disorders of Orgasm in Women Committee, there were four experts
      from two countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of
      evidence-based medical literature, widespread internal committee discussion,
      public presentation and debate. RESULTS: Female Orgasmic Disorder, the second
      most frequently reported women's sexual problem is considered to be the
      persistent or recurrent delay in, or absence of, orgasm following a normal sexual
      excitement phase that causes marked distress or interpersonal difficulty (DSM
      IV). Empirical treatment outcome research is available for cognitive behavioral
      and pharmacological approaches. Cognitive-behavioral therapy for anorgasmia
      promotes attitude and sexually-relevant thought changes and anxiety reduction
      using behavioral exercises such as directed masturbation, sensate focus, and
      systematic desensitization treatments as well as sex education, communication
      skills training, and Kegel exercises. To date there are no pharmacological agents
      trials (i.e., bupropion, granisetron, and sildenafil) proven to be beneficial
      beyond placebo in enhancing orgasmic function in women diagnosed with Female
      Orgasmic Disorder. CONCLUSIONS: More research is needed in understanding
      management of women with orgasmic dysfunction.

PMID- 16422986
TI  - Endocrine aspects of sexual dysfunction in men.
AB  - INTRODUCTION: Endocrine disorders of sex steroid hormones may adversely affect
      men's sexual function. Aim. To provide expert opinions/recommendations concerning
      state-of-the-art knowledge for the pathophysiology, diagnosis and treatment of
      endocrinologic sexual medicine disorders. METHODS: An International Consultation
      in collaboration with the major urology and sexual medicine associations
      assembled over 200 multidisciplinary experts from 60 countries into 17
      committees. Committee members established specific objectives and scopes for
      various male and female sexual medicine topics. The recommendations concerning
      state-of-the-art knowledge in the respective sexual medicine topic represent the
      opinion of experts from five continents developed in a scientific and debate
      process. Concerning the Endocrine committee, there were eight experts from seven
      countries. MAIN OUTCOME MEASURE: Expert opinions/recommendations are based on
      grading of evidence-based medical literature, extensive internal committee
      discussion over 2 years, public presentation and deliberation. RESULTS:
      Hypogonadism is a clinical and biochemical syndrome characterized by a deficiency
      in serum androgen levels which may decrease sexual interest, quality of erections
      and quality of life. Biochemical investigations include testosterone and either
      bioavailable or calculated free testosterone; prolactin should be considered when
      hypogonadism has been documented. If clinically indicated, androgen therapy
      should maintain testosterone within the physiological range avoiding
      supraphysiologic values. Digital rectal examination and determination of serum
      prostate specific antigen values are mandatory prior to therapy and regularly
      thereafter. Androgen therapy is usually long-term requiring regular follow-up,
      frequent monitoring of blood levels and beneficial and adverse therapeutic
      responses. CONCLUSIONS: Safe and effective treatments for endocrinologic sexual
      medicine disorders examined by prospective, placebo-controlled, multi
      institutional clinical trials are needed.

PMID- 16422987
TI  - Endocrine aspects of female sexual dysfunction.
AB  - INTRODUCTION: Various endogenous hormones, including estrogen, testosterone,
      progesterone and prolactin, may influence female sexual function. AIM: To provide
      recommendations for the diagnosis and treatment of women with endocrinologic
      sexual difficulties. METHODS: The Endocrine Aspects of Female Sexual Dysfunction
      Committee was part of a multidisciplinary International Consultation. It included
      four experts from two countries and several peer reviewers. MAIN OUTCOME MEASURE:
      Expert opinion was based on committee discussion, a comprehensive literature
      review and evidence-based grading of available publications. RESULTS: The impact
      of hormones on female sexual function and their etiological roles in dysfunction
      is complex. Research data are limited as studies have been hampered by lack of
      precise hormonal assays and validated measures of sexual function in women. Sex
      steroid insufficiency is associated with urogenital atrophy and may also
      adversely affect central sexual thought processes. Systemic estrogen/estrogen
      progestin therapy alleviates climacteric symptoms but there is no evidence that
      this therapy specifically improves hypoactive sexual desire disorder (HSDD) in
      premenopausal or postmenopausal women. Exogenous testosterone has been shown in
      small randomized controlled trials (RCT) to improve sexual desire, arousal and
      sexual satisfaction in both premenopausal and postmenopausal women. However, as
      there is no biochemical measure that clearly identifies who to treat, use of
      exogenous testosterone should be considered only after other causes of HSDD have
      been excluded, such as depression, relationship problems and ill health. The
      clinical assessment of HSDD should include detailed medical, gynecologic, sexual
      and psychosocial history and physical examination including the external/internal
      genitalia. Hormonal therapy should be individualized and risks/benefits fully
      discussed, and all treated women should be carefully followed up and monitored
      for therapeutic side effects. CONCLUSIONS: There is a need for prospective, multi
      institutional clinical trials to define safe and effective endocrine treatments
      for female sexual dysfunction.

PMID- 16422988
TI  - Standards for clinical trials in male sexual dysfunction: erectile dysfunction
      and rapid ejaculation.
AB  - INTRODUCTION: The introduction of safe and effective therapies for sexual
      dysfunctions depend upon appropriate clinical protocol design, study procedures,
      data collection and analysis. AIM: To provide recommendations/guidelines
      concerning state-of-the-art knowledge for standards for clinical trials in sexual
      dysfunction in men, particularly in the areas of erectile dysfunction and rapid
      ejaculation. METHODS: An International Consultation in collaboration with the
      major urology and sexual medicine associations assembled over 200
      multidisciplinary experts from 60 countries into 17 committees. Committee members
      established specific objectives and scopes for various male and female sexual
      medicine topics. The recommendations concerning state-of-the-art knowledge in the
      respective sexual medicine topic represent the opinion of experts from five
      continents developed in a process over a 2-year period. Concerning the Standards
      for Clinical Trials in Male Sexual Dysfunction Committee, there were six experts
      from four countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of
      evidence-based medical literature, widespread internal committee discussion,
      public presentation and debate. RESULTS: Drug development requires a multiphased
      approach. Phase 1 studies investigate multiple-dose safety, tolerability and
      pharmacokinetic issues. Phase 2 programs explore dose ranging (lowest effective,
      maximally tolerated and toxic doses). Phase 3 trials provide the substantial
      evidence including drug-drug interaction data and studies in special populations.
      Clinical studies require validated outcome assessment instruments conducted in
      defined but representative patient populations. Daily diaries or per-event
      questionnaires are patient-reported outcomes that assist in retrospective
      questionnaire interpretation. A qualified biostatistician should calculate the
      sample power for the trial, type of statistical model and design employed, use of
      covariate or subgroup analyses, and calculation of effect sizes. CONCLUSIONS:
      More research is needed in developing standards for use in the development of
      clinical trials and outcomes assessment researching either erectile dysfunction
      or rapid ejaculation.

PMID- 16422989
TI  - Standards for clinical trials in sexual dysfunctions of women: research designs
      and outcomes assessment.
AB  - INTRODUCTION: Clinical trials on sexual dysfunctions in women are limited in
      spite of the fact that sexual dysfunctions are likely more common in women than
      in men. Currently there are no medications approved for treatment in women, and
      limited data on drug efficacy or psychological efficacy in well-controlled
      studies. AIM: To provide recommendations/guidelines concerning state-of-the-art
      knowledge for the research design and outcome assessment standards for clinical
      trials in women's sexual dysfunctions. METHODS: An International Consultation in
      collaboration with the major urology and sexual medicine associations assembled
      over 200 multidisciplinary experts from 60 countries into 17 committees.
      Committee members established specific objectives and scopes for various male and
      female sexual medicine topics. The recommendations concerning state-of-the-art
      knowledge in the respective sexual medicine topic represent the opinion of
      experts from five continents developed in a process over a 2-year period.
      Concerning the Standards for Clinical Trials in Women's Sexual Dysfunctions
      Committee, there were seven experts from two countries. MAIN OUTCOME MEASURE:
      Expert opinion was based on grading of evidence-based medical literature,
      widespread internal committee discussion, public presentation and debate.
      RESULTS: A comprehensive update was created which included references and
      recommended guidelines for rationale and design of clinical trials, study
      populations, outcome assessments, protocol design and implementation, data
      analysis and reporting, as well as ethical and clinical issues related to sexual
      dysfunction research. CONCLUSIONS: There is a need for more research in
      developing standards to be used when performing clinical trials and outcomes
      assessment research in sexual dysfunctions of women.

PMID- 16422990
TI  - The penile implant for erectile dysfunction.
AB  - INTRODUCTION: Penile prostheses, introduced as the first effective organic
      treatment for erectile dysfunction over three decades ago, have an important role
      in the treatment of erectile dysfunction when other nonprosthetic treatment
      options have proven unsatisfactory. Although they are the least chosen and most
      invasive treatment option, they have the highest satisfaction rate of all
      available ED options and provide a predictable and reliable result. AIM: To
      provide recommendations/guidelines concerning state-of-the-art knowledge for
      utilization of the penile prosthesis in the management of men with erectile
      dysfunction. METHODS: An International Consultation in collaboration with the
      major sexual medicine associations assembled over 200 multidisciplinary experts
      from 60 countries into 17 committees. Committee members established specific
      objectives and scopes for various sexual medicine topics. The recommendations
      concerning state-of-the-art knowledge in the respective sexual medicine topic
      represent the opinion of experts from five continents developed in a process over
      a 2-year period. There were 10 experts from seven countries concerning the Penile
      Implant for Erectile Dysfunction. MAIN OUTCOME MEASURE: Expert opinion was based
      on grading of evidence-based medical literature, widespread internal committee
      discussion, public presentation and debate. RESULTS: Recommendations/guidelines
      for penile prosthesis (hydraulic, semi-rigid and soft silicone) insertion for
      management of men with erectile dysfunction were updated. Consensed issues
      included: criteria for patient selection, informed consent procedures, strategies
      for preoperative preparation, operative incisions/technical considerations and
      outcome results in terms of patient satisfaction and device survival. Updated
      information was reviewed concerning therapies for device failures, device
      insertion in scarred corporal bodies and strategies for managing implant
      infections. CONCLUSIONS: There is a need for more research in developing
      management strategies for insertion of penile prostheses in men with ED.

PMID- 16422991
TI  - Peyronie's disease.
AB  - INTRODUCTION: Peyronie's disease is a sexual medicine condition that may
      adversely affect male sexual function. AIM: To provide expert
      opinions/recommendations concerning state-of-the-art knowledge for the
      pathophysiology, diagnosis and treatment of Peyronie's disease. METHODS: An
      International Consultation in collaboration with the major urology and sexual
      medicine associations assembled over 200 multidisciplinary experts from 60
      countries into 17 committees. Committee members established specific objectives
      and scopes for various male and female sexual medicine topics. The
      recommendations concerning state-of-the-art knowledge in the respective sexual
      medicine topic represent the opinion of experts from five continents developed in
      a scientific and debate process. Concerning the Peyronnie's disease committee,
      there were 10 experts from six countries. MAIN OUTCOME MEASURE: Expert
      opinions/recommendations are based on grading of evidence-based medical
      literature, extensive internal committee discussion over 2 years, public
      presentation and deliberation. RESULTS: Peyronie's disease is characterized by an
      inflammatory response beneath the tunica albuginea with fibroblast proliferation
      forming a thickened fibrous plaque that may cause penile pain, penile curvature
      and erectile dysfunction. Medical treatments have been described but few
      prospective controlled trials have revealed significant clinical benefits.
      Surgical treatments (penile plication, Nesbit excision, plaque incision and
      grafting and penile prosthesis insertion) should be considered after Peyronie's
      disease has stabilized. Surgical outcome studies reveal that a stable deformity
      is best corrected with the least postoperative ED by a Nesbit procedure. Plaque
      incision and grafting should be reserved for men with good erectile function and
      marked penile shortening although there is a higher prevalence of postoperative
      ED. Implantation of a penile prosthesis is an excellent option for men with an
      accompanying erectile deficit. CONCLUSIONS: Safe and effective treatments for
      Peyronie's disease examined by prospective, placebo-controlled, multi
      institutional clinical trials are needed.

PMID- 16422993
TI  - Review article: complementary and alternative therapies for inflammatory bowel
      disease.
AB  - Complementary and alternative medicine includes a wide range of practices and
      therapies outside the realms of conventional western medicine. Despite a lack of
      scientific data in the form of controlled trials for either efficacy or safety of
      complementary and alternative medicine, use by patients with inflammatory bowel
      disease, particularly of herbal therapies, is widespread and increasing. There is
      limited controlled evidence indicating efficacy of traditional Chinese medicines,
      aloe vera gel, wheat grass juice, Boswellia serrata and bovine colostrum enemas
      in ulcerative colitis. Encouraging results have also been reported in small
      studies of acupuncture for Crohn's disease and ulcerative colitis. Contrary to
      popular belief, natural therapies are not necessarily safe: fatal hepatic and
      irreversible renal failure have occurred with some preparations and interactions
      with conventional drugs are potentially dangerous. There is a need for further
      controlled clinical trials of the potential efficacy of complementary and
      alternative approaches in inflammatory bowel disease, together with enhanced
      legislation to maximize their quality and safety.

PMID- 16422992
TI  - Priapism.
AB  - INTRODUCTION: There are three different types of priapism: low-flow, ischemic,
      anoxic or veno-occlusive priapism; high-flow, arterial or nonischemic priapism;
      and recurrent or stuttering priapism. AIM: To provide recommendations/guidelines
      concerning state-of-the-art knowledge for the diagnosis and treatment of
      priapism. METHODS: An International Consultation in collaboration with the major
      urology and sexual medicine associations assembled over 200 multidisciplinary
      experts from 60 countries into 17 committees. Committee members established
      specific objectives and scopes for various male and female sexual medicine
      topics. The recommendations concerning state-of-the-art knowledge in the
      respective sexual medicine topic represent the opinion of experts from five
      continents developed in a process over a 2-year period. Concerning the Priapism
      Committee, there were 10 experts from six countries. MAIN OUTCOME MEASURE: Expert
      opinion was based on grading of evidence-based medical literature, widespread
      internal committee discussion, public presentation and debate. RESULTS:
      Concerning ischemic priapism, persistent cavernous smooth muscle relaxation and
      failure of contraction is a compartment syndrome with increasing intracavernosal
      anoxia, rising pCO2 and acidosis. Urgent medical attention should be sought for
      an erection lasting >4 hours; 90% with priapism >24 hours develop complete
      erectile dysfunction. After diagnosis and counselling, intracavernosal aspiration
      and alpha-blockers should precede surgical shunting. Concerning high-flow
      priapism (congenital, traumatic or iatrogenic), intervention is not urgent and
      often unnecessary. Definitive management is by selective embolization with
      autologous blood clot. Concerning recurrent/stuttering priapism, the
      pathophysiology may be central or local (sickle cell disease). Management needs
      to be individualized; androgen deprivation has proved useful but has adverse
      effects. CONCLUSIONS: There is need for prospective, clinical trials to define
      safe and effective management strategies for patients with low-flow, high-flow or
      recurrent priapism.

PMID- 16422994
TI  - Review article: non-biological liver support in liver failure.
AB  - Liver failure, whether acute or acute-on-chronic, remains an important cause of
      morbidity and mortality. The lack of liver detoxification, metabolic and
      regulatory functions of the liver leads to life-threatening complications, such
      as renal failure, altered immune response, hepatic coma and systemic haemodynamic
      dysfunction, eventually culminating in multiorgan failure. Current medical
      therapy involves the management of the precipitating event and treatment of
      complications until the liver eventually recovers, leaving us with no other
      treatment options than transplantation if these attempts fail. However, the
      shortage in cadaveric organs and other transplant-related problems, have prompted
      the need for alternative methods to provide liver support. As liver failure is
      often potentially reversible, considerable effort has been invested in the
      development of liver support systems. Currently, most of the experience is
      available for non-biological support systems. They represent the focus of this
      review, which aims to define the goals of liver support, to describe the design
      of the different existing devices and to analyse the available data to determine
      their current status in the management of patients with liver failure.

PMID- 16422995
TI  - Influence of citalopram, a selective serotonin reuptake inhibitor, on oesophageal
      hypersensitivity: a double-blind, placebo-controlled study.
AB  - Background Tricyclic antidepressants, which have multiple pharmacological
      influences, have a therapeutic effect in non-cardiac chest pain, but selective
      serotonin reuptake inhibitors have a single pharmacological effect. Aim To
      evaluate the acute effect of citalopram on oesophageal hypersensitivity. Methods
      On two separate occasions, 10 healthy subjects (seven men, mean age 25 years)
      with established oesophageal hypersensitivity, underwent oesophageal manometry
      with evaluation of mechanical and chemical sensitivity. Subjects received placebo
      or citalopram 20 mg i.v. in a randomized, crossover, double-blind fashion.
      Results Citalopram did not alter oesophageal motility. Citalopram significantly
      increased the threshold inducing first perception (4.6+/-0.3 vs. 6.7+/-0.4 mL,
      P<0.005) and discomfort (8.6+/-0.4 vs. 9.9+/-0.6 mL, P<0.01) during balloon
      distention. It also significantly prolonged the acid perfusion time to induce
      perception of heartburn (6.0+/-0.9 vs. 10.7+/-0.6 min, P<0.005) and discomfort
      (12.2+/-0.8 vs. 16.7+/-0.7 mL, P<0.001). Seven subjects experienced a
      retrosternal sensation during edrophonium provocation with placebo, and this was
      reduced to two of 10 after citalopram (P=0.02). Conclusions Acute administration
      of citalopram significantly lowers chemical and mechanical oesophageal
      sensitivity in oesophageal hypersensitivity, without altering the motility.

PMID- 16422996
TI  - Cost-of-disease analysis in patients with gastro-oesophageal reflux disease and
      Barrett's mucosa.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common and frequently
      chronic condition that causes considerable costs. AIM: To estimate the economic
      burden caused by patients with erosive and non-erosive reflux disease, and
      Barrett's oesophagus. METHODS: The Progression of Gastro-oesophageal Reflux
      Disease study includes a total of 6,215 patients. At baseline, patients were
      categorized as non-erosive reflux disease, erosive reflux disease, or Barrett's
      oesophagus according to endoscopic findings alone or as confirmed by histology.
      Direct and indirect disease-related costs were calculated based on 5,273 patients
      with complete information in the second year of the study. RESULTS: A total of
      73% of the Progression of Gastro-oesophageal Reflux Disease patients had taken
      GERD medication, 61% had visited a doctor, and 2% had been hospitalized because
      of GERD during the previous 12 months. Of all employed persons, 6% reported days
      off work because of GERD. This health resource utilization caused direct costs of
      342+/-864 (mean+/-s.d.) and indirect costs of 40+/-473 per patient and year.
      Total costs for patients with Barrett's oesophagus or erosive reflux disease were
      higher than those for patients with non-erosive reflux disease. CONCLUSION:
      Patients with GERD frequently need long-term medication and doctor care. The
      disorder is associated with a considerable health economic burden to society.

PMID- 16422997
TI  - Long-term prognosis in Crohn's disease: factors that affect quality of life.
AB  - BACKGROUND: There are many studies investigating quality of life in recently
      diagnosed patients and following surgery for Crohn's disease, but there are none
      investigating quality of life changes with disease duration. The response shift
      model suggests quality of life improves with time following diagnosis. AIM: To
      assess how well the model applies to patients with Crohn's disease. METHODS: The
      Cardiff Crohn's disease database contains data on all patients diagnosed there
      since 1934. Three hundred and ninety four patients diagnosed before 1 January
      1985 were traced and the mortality status on 31 December 2004 established. Two
      hundred and eleven still living were sent quality of life questionnaires. Two
      hundred and eighty five questionnaires were sent to patients with varying disease
      duration attending out-patient clinics in Leicester. RESULTS: Eighty-nine valid
      replies were received from Cardiff, 63 from Leicester patients diagnosed over 20
      years, 69 from Leicester patients diagnosed <10 years. There was no difference in
      quality of life between newly diagnosed and established patients. Of greatest
      concern was possible need for ostomy, uncertain nature of disease, and lack of
      energy. Stepwise regression showed that increased disease severity, older age and
      smoking adversely affect quality of life. DISCUSSION: Quality of life is equally
      poor in patients with established disease as in those newly diagnosed, and
      directly correlates with disease severity. The response shift model may not be
      applicable in Crohn's disease.

PMID- 16422998
TI  - Pharmacokinetics and pharmacodynamic action of budesonide in children with
      Crohn's disease.
AB  - BACKGROUND: Budesonide is effective as initial therapy of mild to moderate
      Crohn's disease in adults. Superior tolerability to conventional corticosteroids
      might be attributed to extensive first-pass metabolism of budesonide by
      cytochrome P450 3A. AIM: To evaluate biotransformation and pharmacodynamic action
      of budesonide in children. METHODS: Drug disposition and effects on endogenous
      cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after
      first intake of 3 mg budesonide (single dose), and again after 1 week of thrice
      daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent
      metabolites were analysed in blood and urine. RESULTS: Pharmacokinetic parameters
      of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/
      5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall
      systemic elimination of budesonide reflected by clearance and half-life was not
      different between children and adults. After 1 week of treatment reversible
      adrenal suppression was observed - most pronounced in children aged below 12
      years. CONCLUSIONS: Disposition of oral budesonide appears to be similar between
      children and adults, but the doctor has to be aware of an increased risk for
      adrenal suppression in paediatric patients.

PMID- 16422999
TI  - Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and
      ribavirin in clinical practice.
AB  - BACKGROUND: Pegylated interferon alfa-2a (40 KD) plus ribavirin therapy induces
      sustained virological response rates up to 63% in randomized-controlled trials.
      AIM: To conduct a prospective open-label programme to examine the efficacy and
      safety of this therapy in routine clinical practice. METHODS: Treatment-naive
      patients with chronic hepatitis C received, at the discretion of the
      investigator, pegylated interferon alfa-2a 180 microg/week + ribavirin 800 mg/day
      for 24 or 48 weeks. In total, 508 patients were enrolled [334 non-cirrhotic; 174
      cirrhotic (defined as stage F3 and F4)]. RESULTS: In genotype 1 patients treated
      for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and
      34% in cirrhotics. Sustained virological response rates in genotype 2 or 3 non
      cirrhotics were 79% (24 weeks) and 72% (48 weeks). Corresponding values for
      cirrhotic genotype 2/3 were 66% and 44%. The negative predictive value of an
      early virological response at week 12 was 94%. Predictive factors for sustained
      virological response on multivariate analysis were genotype (2/3 vs. 1), low
      viral load and degree of fibrosis. Rates of serious adverse events (<or=5%) and
      adverse events inducing withdrawal (<or=8%) were comparable with the phase III
      trials. CONCLUSION: Efficacy and safety of pegylated interferon alfa-2a +
      ribavirin in clinical practice is comparable with results of randomized
      controlled trials.

PMID- 16423000
TI  - Cost-effectiveness analysis of lamivudine and adefovir dipivoxil in the treatment
      of patients with HBeAg-negative chronic hepatitis B.
AB  - AIM: To estimate the cost-effectiveness over a 4-year duration of lamivudine and
      adefovir dipivoxil for patients with hepatitis B 'e' antigen-negative chronic
      hepatitis B. METHODS: A decision analysis model has been used to perform a cost
      effectiveness analysis of lamivudine and adefovir dipivoxil from the perspective
      of the Spanish Public Health System. Data were obtained from clinical trials.
      RESULTS: For the base-case, the total estimated cost per patient treated with
      lamivudine or adefovir dipivoxil for 4 years was 11,457 and 21,939 respectively.
      Virological response at year 4 for the lamivudine arm was 40.4% and 78.0% for the
      adefovir dipivoxil arm. The average cost-effectiveness ratio (cost per responding
      patient at year 4) was 28,375 for the lamivudine arm and 28,132 for the adefovir
      dipivoxil arm. The incremental cost-effectiveness ratio of adefovir dipivoxil vs.
      lamivudine (cost per additional responding patient with adefovir dipivoxil) was
      27,872, demonstrating that this cost was slightly lower than the average cost
      effectiveness ratios of adefovir dipivoxil or lamivudine. The sensitivity
      analysis demonstrated that the factors that most influence the cost-effectiveness
      were the response to adefovir dipivoxil and lamivudine at year 4. CONCLUSION:
      Long-term treatment with adefovir dipivoxil is a cost-effective strategy in
      patients with chronic hepatitis B 'e' antigen-negative hepatitis.

PMID- 16423001
TI  - Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy
      as second-line treatment of resistant Helicobacter pylori infection.
AB  - AIM: To test the efficacy of levofloxacin-based second-line therapy for resistant
      Helicobacter pylori infection. METHODS: One hundred and six patients who failed
      H. pylori eradication were randomized to receive (i) lansoprazole 30 mg,
      amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or
      (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth
      subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days
      (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath
      test. RESULTS: Intention-to-treat and per-protocol H. pylori eradication rates
      were 57/60% for the LAL group and 71/76% for the quadruple group respectively.
      Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found
      in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to
      treatment failure in the LAL group. For patients with dual resistance to
      metronidazole and clarithromycin, the eradication rates were 79% in the LAL group
      (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). CONCLUSION:
      Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable
      with quadruple therapy in efficacy. Subjects, especially those with dual
      resistance to metronidazole and clarithromycin, may consider levofloxacin-based
      therapy for levofloxacin-sensitive strains.

PMID- 16423002
TI  - Primary clarithromycin resistance in Italy assessed on Helicobacter pylori DNA
      sequences by TaqMan real-time polymerase chain reaction.
AB  - BACKGROUND: Helicobacter pylori clarithromycin resistance is increasing worldwide
      and different mutations are involved in its mechanisms. Recently, molecular
      methods have been proposed to assess these mutations. AIM: To assess prevalence
      of primary clarithromycin resistance in two Italian areas, and the distribution
      of involved mutations, by using a novel method for real-time polymerase chain
      reaction. METHODS: Two hundred and thirty-two H. pylori-positive patients
      undergoing oesophagogastroduodenoscopy in two Italian towns (Rome, centre Italy;
      Foggia, south Italy) were enrolled. Helicobacter pylori infection was detected by
      histology, rapid urease and urea breath tests. Clarithromycin resistance was
      assessed by TaqMan real-time polymerase chain reaction on paraffin-embedded
      antral biopsies. Results Primary clarithromycin resistance was detected in 62
      (26.7%) patients. Its prevalence did not differ between the two areas (31.5%,
      centre vs. 23.3%, south; P=0.17) and between non-ulcer dyspepsia and peptic ulcer
      patients (28.4% vs. 20.7%, P=0.2). The A2143G point mutation was detected in 35
      (56.4%) patients, A2142G in 14 (22.6%), A2142C in eight (12.9%), whilst a double
      mutation (A2143G plus A2142C or A2142G) was present in the remaining five (8.1%)
      cases. CONCLUSIONS: Our study found that primary clarithromycin resistance is
      highly prevalent in both central and southern Italy, and that A2143G is the most
      frequent point mutation involved in these areas.

PMID- 16423003
TI  - Three-year oral pantoprazole administration is effective for patients with
      Zollinger-Ellison syndrome and other hypersecretory conditions.
AB  - BACKGROUND: Zollinger-Ellison syndrome and idiopathic hypersecretion are
      gastrointestinal hypersecretory conditions requiring long-term maintenance. AIMS:
      The safety and efficacy data for short-term (6-month) treatment of Zollinger
      Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were
      previously published. This study extends the initial observations to 3 years.
      METHODS: The primary efficacy end point for this report was the control of
      gastric acid secretion in the last hour before the next dose of oral pantoprazole
      (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid-reducing
      surgery). Dose titration was permitted to a maximum of 240 mg per 24 h. RESULTS:
      Twenty-four subjects completed the study. The acid output of 28 of 34 subjects
      was controlled at initial enrolment. The mean acid output rates were <10 mmol/h
      throughout the 36 months of treatment for 90-100% of the patients. The majority
      of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36
      months (acid output was controlled in 24 of 24 subjects). Pantoprazole was
      generally well tolerated with minimal adverse events reported. CONCLUSIONS:
      Maintenance oral pantoprazole therapy up to 3 years at dosages of 40-120 mg b.d.
      was effective and well tolerated in patients with Zollinger-Ellison syndrome and
      other hypersecretory conditions.

PMID- 16423007
TI  - Protecting sausages with bacteria instead of salt.

PMID- 16423004
TI  - Thalidomide: an effective anabolic agent in gastrointestinal cancer cachexia.

PMID- 16423008
TI  - Environmental tuning of mutation rates.
AB  - Through their life cycles, bacteria experience many different environments in
      which the relationship between available energy resources and the frequency and
      the nature of various stresses is highly variable. In order to survive in such
      changeable environments, bacteria must balance the need for nutritional
      competence with stress resistance. In Escherichia coli natural populations, this
      is most frequently achieved by changing the regulation of the RpoS sigma factor
      dependent general stress response. One important secondary consequence of altered
      regulation of the RpoS regulon is the modification of mutation rates. For
      example, under nutrient limitation during stationary phase, the high
      intracellular concentration of RpoS diminishes nutritional competence, increases
      stress resistance, and, by downregulating the mismatch repair system and
      upregulating [corrected] the expression of the dinB gene (coding for PolIV
      translesion synthesis polymerase) increases mutation rates. The reduction of the
      intracellular concentration of RpoS has exactly opposite effects on nutritional
      competence, stress resistance and mutation rates. Therefore, the natural
      selection that favours variants having the highest fitness under different
      environmental conditions results in high variability of stress-associated
      mutation rates in those variants.

PMID- 16423009
TI  - daime, a novel image analysis program for microbial ecology and biofilm research.
AB  - Combinations of microscopy and molecular techniques to detect, identify and
      characterize microorganisms in environmental and medical samples are widely used
      in microbial ecology and biofilm research. The scope of these methods, which
      include fluorescence in situ hybridization (FISH) with rRNA-targeted probes, is
      extended by digital image analysis routines that extract from micrographs
      important quantitative data. Here we introduce daime (digital image analysis in
      microbial ecology), a new computer program integrating 2-D and 3-D image analysis
      and visualization functionality, which has previously not been available in a
      single open-source software package. For example, daime automatically finds 2-D
      and 3-D objects in images and confocal image stacks, and offers special functions
      for quantifying microbial populations and evaluating new FISH probes. A novel
      feature is the quantification of spatial localization patterns of microorganisms
      in complex samples like biofilms. In combination with '3D-FISH', which preserves
      the 3-D structure of samples, this stereological technique was applied in a proof
      of principle experiment on activated sludge and provided quantitative evidence
      that functionally linked ammonia and nitrite oxidizers cluster together in their
      habitat. This image analysis method complements recent molecular techniques for
      analysing structure-function relationships in microbial communities and will help
      to characterize symbiotic interactions among microorganisms.

PMID- 16423010
TI  - Nitrosospira spp. can produce nitrous oxide via a nitrifier denitrification
      pathway.
AB  - Nitrous oxide (N(2)O) emission from soils is a major contributor to the
      atmospheric loading of this potent greenhouse gas. It is thought that autotrophic
      ammonia oxidizing bacteria (AOB) are a significant source of soil-derived N(2)O
      and a denitrification pathway (i.e. reduction of NO(2) (-) to NO and N(2)O), so
      called nitrifier denitrification, has been demonstrated as a N(2)O production
      mechanism in Nitrosomonas europaea. It is thought that Nitrosospira spp. are the
      dominant AOB in soil, but little information is available on their ability to
      produce N(2)O or on the existence of a nitrifier denitrification pathway in this
      lineage. This study aims to characterize N(2)O production and nitrifier
      denitrification in seven strains of AOB representative of clusters 0, 2 and 3 in
      the cultured Nitrosospira lineage. Nitrosomonas europaea ATCC 19718 and ATCC
      25978 were analysed for comparison. The aerobically incubated test strains
      produced significant (P < 0.001) amounts of N(2)O and total N(2)O production
      rates ranged from 2.0 amol cell(-1) h(-1), in Nitrosospira tenuis strain NV12, to
      58.0 amol cell(-1) h(-1), in N. europaea ATCC 19718. Nitrosomonas europaea ATCC
      19718 was atypical in that it produced four times more N(2)O than the next
      highest producing strain. All AOB tested were able to carry out nitrifier
      denitrification under aerobic conditions, as determined by production of (15)N
      N(2)O from applied (15)N-NO(2) (-). Up to 13.5% of the N(2)O produced was derived
      from the exogenously applied (15)N-NO(2) (-). The results suggest that nitrifier
      denitrification could be a universal trait in the betaproteobacterial AOB and its
      potential ecological significance is discussed.

PMID- 16423011
TI  - Microbial community structure in polluted Baltic Sea sediments.
AB  - Nearly half the seabed of the Baltic Proper is incapable of supporting life of
      higher organisms as a consequence of oxygen depletion resulting from
      eutrophication. However, these areas are actually teeming with microbial life.
      Here we used terminal-restriction fragment length polymorphism (T-RFLP) to
      investigate the dominant archaeal and bacterial groups, with respect to community
      structure, in surface layers of bottom sediments of the Baltic Sea along a
      coastal pollution gradient. Both archaeal and bacterial communities formed
      distinct clusters along the pollution gradient and the community compositions
      were different at the polluted sites compared with the relatively clean reference
      sites. The structures of the bacterial communities were most strongly correlated
      to water depth, followed by organic carbon, oxygen, salinity and silicate levels.
      In contrast, the structures of the archaeal communities were most strongly
      correlated to oxygen, salinity, organic carbon, silicate and nitrate levels. Some
      members of the microbial communities were identified using a combination of
      traditional and molecular approaches. Isolates obtained on different culture
      media were identified by partial sequencing of their 16S rRNA genes and some
      novel species were found. In addition, we developed a computer program, aplaus,
      to elucidate the putative identities of the most dominant community members by T
      RFLP.

PMID- 16423012
TI  - Effect of above-ground plant species on soil microbial community structure and
      its impact on suppression of Rhizoctonia solani AG3.
AB  - The extent of soil microbial diversity is seen to be critical to the maintenance
      of soil health and quality. Different agricultural practices are able to affect
      soil microbial diversity and thus the level of suppressiveness of plant diseases.
      In a 4-year field experiment, we investigated the microbial diversity of soil
      under different agricultural regimes. We studied permanent grassland, grassland
      turned into arable land, long-term arable land and arable land turned into
      grassland. The diversity of microbial communities was described by using
      cultivation-based and cultivation-independent methods. Both types of methods
      revealed differences in the diversities of soil microbial communities between
      different treatments. The treatments with higher above-ground biodiversity
      generally maintained higher levels of microbial diversity. Moreover, a positive
      correlation between suppression of Rhizoctonia solani AG3 and microbial diversity
      was observed. Permanent (species-rich) grassland and grassland turned into maize
      stimulated higher microbial diversities and higher levels of suppressiveness of
      R. solani AG3 compared with the long-term arable land. Effects of agricultural
      practices on Bacillus and Pseudomonas communities were also observed and clear
      correlations between the levels of suppressiveness and the diversities of these
      bacterial groups were found. This study highlighted the importance of
      agricultural management regime for soil microbial community structure and
      diversity as well as the level of soil suppressiveness.

PMID- 16423013
TI  - Alteration and resilience of the soil microbial community following compost
      amendment: effects of compost level and compost-borne microbial community.
AB  - Compost amendment has been reported to impact soil microbial activities or
      community composition. However, little information is available on (i) to what
      extent compost amendment concurrently affects the activity, size and composition
      of soil microbial community, (ii) the relative effect of the addition of a
      material rich in organic matter versus addition of compost-borne microorganisms
      in explaining the effects of amendment and (iii) the resilience of community
      characteristics. We compared five treatments in microcosms: (i) control soil (S),
      (ii) soil + low level of compost (Sc), (iii) soil + high level of compost (SC),
      (iv) sterilized soil + high level of compost [(S)C] and (v) soil + high level of
      sterilized compost [S(C)]. The actual C mineralization rate, substrate-induced
      respiration, size of microbial community (biomass and heterotrophic cells
      number), and structure of total microbial (phospholipid fatty acids) and
      bacterial (automated ribosomal intergenic spacer analysis, A-RISA) communities
      were surveyed during 6 months after amendment. Our results show that (i) compost
      amendment affected the activity, size and composition of the soil microbial
      community, (ii) the effect of compost amendment was mainly due to the
      physicochemical characteristics of compost matrix rather than to compost-borne
      microorganisms and (iii) no resilience of microbial characteristics was observed
      6-12 months after amendment with a high amount of compost.

PMID- 16423014
TI  - Diversity and phylotype consistency of bacteria in the guts of three bee species
      (Apoidea) at an oilseed rape field.
AB  - The gut of insects may harbour one of the largest reservoirs of a yet unexplored
      microbial diversity. To understand how specific insects select for their own
      bacterial communities, the structural diversity and variability of bacteria found
      in the gut of different bee species was analysed. For three successive years,
      adults and larvae of Apis mellifera ssp. carnica (honey bee), and Bombus
      terrestris (bumble bee), as well as larvae of Osmia bicornis (red mason bee) were
      collected at a flowering oilseed rape field. Total DNA was extracted from gut
      material and the bacterial diversity was analysed, independent of cultivation, by
      genetic profiling with single-strand conformation polymorphism (SSCP) of
      polymerase chain reaction (PCR)-amplified partial 16S rRNA genes. The SSCP
      profiles were specific for all bee species and for larvae and adults. Qualitative
      and quantitative differences were found in the bacterial community structure of
      larvae and adults of A. mellifera, but differences in B. terrestris were mainly
      quantitative. Sequencing of the PCR products revealed a dominance of Alpha-, Beta
      , and Gammaproteobacteria, Bacteroidetes, and Firmicutes in all bee species.
      Single-strand conformation polymorphism profiles suggested a higher abundance and
      diversity of lactobacilli in adults of A. mellifera than in larvae. Further
      phylogenetic analyses indicated common bacterial phylotypes for all three bee
      species, e.g. those related to Simonsiella, Serratia, and Lactobacillus. Clades
      related to Delftia acidovorans, Pseudomonas aeruginosa or Lactobacillus
      intestinalis only contained sequences from larvae. Several of the bee-specific
      clusters also contained identical or highly similar sequences from bacteria
      detected in other A. mellifera subspecies from South Africa, suggesting the
      existence of cosmopolitan gut bacteria in bees.

PMID- 16423015
TI  - Genomic comparisons among gamma-proteobacteria.
AB  - Predicted highly expressed (PHX) genes are compared for 16 gamma-proteobacteria
      and their similarities and differences are interpreted with respect to known or
      predicted physiological characteristics of the organisms. Predicted highly
      expressed genes often reflect the organism's predominant lifestyle, habitat,
      nutrition sources and metabolic propensities. This technique allows to predict
      principal metabolic activities of the microorganisms operating in their natural
      habitats. Among our findings is an unusually high number of PHX enzymes acting in
      cell wall biosynthesis, amino acid biosynthesis and replication in the ant
      endosymbiont Blochmannia floridanus. We ascribe the abundance of these PHX genes
      to specific aspects of the relationship between the bacterium and its host.
      Xanthomonas campestris is unique with a very high number of PHX genes acting in
      flagellum biosynthesis, which may play a special role during its pathogenicity.
      Shewanella oneidensis possesses three protein complexes which all can function as
      complex I in the respiratory chain but only the Na(+)-transporting
      NADH:ubiquinone oxidoreductase nqr-2 operon is PHX. The PHX genes of Vibrio
      parahaemolyticus are consistent with the microorganism's adaptation to extremely
      fast growth rates. Comparative analysis of PHX genes from complex environmental
      genomic sequences as well as from uncultured pathogenic microbes can provide a
      novel, useful tool to predict global flux of matter and key intermediates.

PMID- 16423016
TI  - Development and validation of a prototype 16S rRNA-based taxonomic microarray for
      Alphaproteobacteria.
AB  - The microarray approach has been proposed for high throughput analysis of the
      microbial community by providing snapshots of the microbial diversity under
      different environmental conditions. For this purpose, a prototype of a 16S rRNA
      based taxonomic microarray was developed and evaluated for assessing bacterial
      community diversity. The prototype microarray is composed of 122 probes that
      target bacteria at various taxonomic levels from phyla to species (mostly
      Alphaproteobacteria). The prototype microarray was first validated using bacteria
      in pure culture. Differences in the sequences of probes and potential target DNAs
      were quantified as weighted mismatches (WMM) in order to evaluate hybridization
      reliability. As a general feature, probes having a WMM > 2 with target DNA
      displayed only 2.8% false positives. The prototype microarray was subsequently
      tested with an environmental sample, which consisted of an Agrobacterium-related
      polymerase chain reaction amplicon from a maize rhizosphere bacterial community.
      Microarray results were compared to results obtained by cloning-sequencing with
      the same DNA. Microarray analysis enabled the detection of all 16S rRNA gene
      sequences found by cloning-sequencing. Sequences representing only 1.7% of the
      clone library were detected. In conclusion, this prototype 16S rRNA-based
      taxonomic microarray appears to be a promising tool for the analysis of
      Alphaproteobacteria in complex ecosystems.

PMID- 16423017
TI  - DNA extraction procedure: a critical issue for bacterial diversity assessment in
      marine sediments.
AB  - In order to evaluate whether different DNA extraction procedures can affect
      estimates of benthic bacterial diversity, based on 16S rRNA gene terminal
      restriction fragment length polymorphism (T-RFLP) fingerprinting technique, we
      compared two in situ lysis procedures (a SDS-based protocol and a commercial kit
      for DNA recovery) and one cell-extraction protocol on a variety of marine
      sediments. Despite the two in situ lysis procedures resulted in significantly
      different DNA yields (highest with the SDS in situ lysis), estimates of bacterial
      diversity provided a not significantly different ribotype richness, as well as
      similar values of the Shannon-Wiener (H') and Margalef (d) indices of
      biodiversity and of evenness (Pielou index, J). Conversely, the cell-extraction
      procedure for DNA extraction resulted always in a significantly lower ribotype
      richness and diversity. The analysis of similarities (anosim) among the T-RFLP
      electropherograms allowed concluding that ribotypes composition did not change
      significantly using different protocols. However, the analysis of beta-diversity
      (turnover diversity) revealed that a large number of ribotypes was observed
      exclusively with one of the three protocols utilized. When unshared ribotypes
      from in situ lysis and cell extraction were pooled together, total ribotype
      richness resulted much higher (up to 80%). Our results indicate that estimates of
      ribotype diversity based on a single protocol of DNA extraction can significantly
      underestimate the total number of bacterial ribotypes present in the benthic
      domain. We recommend that future studies will not only integrate different DNA
      extraction procedures, but also will explore the possibility of integrating two
      or more different genetic markers in order to increase our ability to detect the
      actual bacterial diversity in environmental samples.

PMID- 16423018
TI  - The active methanotrophic community in hydromorphic soils changes in response to
      changing methane concentration.
AB  - Methanotrophic communities were studied in several periodically water-saturated
      gleyic soils. When sampled, each soil had an oxic upper layer and consumed
      methane from the atmosphere (at 1.75 ppmv). In most gleyic soils the K(m(app))
      values for methane were between 70 and 800 ppmv. These are higher than most
      values observed in dry upland soils, but lower than those measured in wetlands.
      Based on cultivation-independent retrieval of the pmoA-gene and quantification of
      partial pmoA gene sequences, type II (Alphaproteobacteria) methanotrophs of the
      genus Methylocystis spp. were abundant (> 10(7) pmoA target molecules per gram of
      dry soil). Type I (Gammaproteobacteria) methanotrophs related to the genera
      Methylobacter and Methylocaldum/Methylococcus were detected in some soils. Six
      pmoA sequence types not closely related to sequences from cultivated
      methanotrophs were detected as well, indicating that diverse uncultivated
      methanotrophs were present. Three Gleysols were incubated under different mixing
      ratios of (13)C-labelled methane to examine (13)C incorporation into phospholipid
      fatty acids (PLFAs). Phospholipid fatty acids typical of type II methanotrophs,
      16:0 and 18:1omega7c, were labelled with (13)C in all soils after incubation
      under an atmosphere containing 30 ppmv of methane. Incubation under 500 ppmv of
      methane resulted in labelling of additional PLFAs besides 16:0 and 18:1omega7c,
      suggesting that the composition of the active methanotrophic community changed in
      response to increased methane supply. In two soils, 16:1 PLFAs typical of type I
      methanotrophs were strongly labelled after incubation under the high methane
      mixing ratio only. Type II methanotrophs are most likely responsible for
      atmospheric methane uptake in these soils, while type I methanotrophs become
      active when methane is produced in the soil.

PMID- 16423019
TI  - Sequence analysis of three plasmids harboured in Rhodococcus erythropolis strain
      PR4.
AB  - Rhodococcus erythropolis strain PR4 has been isolated as an alkane-degrading
      bacterium. The strain harbours one linear plasmid, pREL1 (271 577 bp) and two
      circular plasmids, pREC1 (104 014 bp) and pREC2 (3637 bp), all with some sequence
      similarities to other Rhodococcus plasmids. For pREL1, pREC1 and pREC2, 298, 102
      and 3 open reading frames, respectively, were predicted. Linear plasmid pREL1 has
      several regions homologous to plasmid pBD2 found in R. erythropolis BD2. Sequence
      analysis of pREL1 and pBD2 identified common metal-resistance genes on both, but
      pREL1 also encodes alkane-degradation genes not found on pBD2, with enzyme
      constituents some of which are quite different from those of other organisms. The
      alkane hydroxylase consisted of a cytochrome P450 monooxygenase, a 2Fe-2S
      ferredoxin, and a ferredoxin reductase. The ferredoxin reductase amino acid
      sequence resembles the AlkT (rubredoxin reductase) sequence. A zinc-containing
      alcohol dehydrogenase further oxydizes alkanols, alkane oxidation products
      catalysed by alkane hydroxylase. Of the circular plasmids, the pREC1 sequence is
      partially similar to the sequence of pREAT701, the virulence plasmid found in
      Rhodococcus equi. pREC1 has no pREAT701 virulence genes and encodes genes for
      beta-oxidation of fatty acids. Thus, joint actions of enzymes encoded by pREL1
      and pREC1 may enable efficient mineralization of alkanes.

PMID- 16423020
TI  - Methylation is the initial reaction in anaerobic naphthalene degradation by a
      sulfate-reducing enrichment culture.
AB  - The sulfate-reducing culture N47 can utilize naphthalene or 2-methylnaphthalene
      as the sole carbon source and electron donor. Here we show that the initial
      reaction in the naphthalene degradation pathway is a methylation to 2
      methylnaphthalene which then undergoes the subsequent oxidation to the central
      metabolite 2-naphthoic acid, ring reduction and cleavage. Specific metabolites
      occurring exclusively during anaerobic degradation of 2-methylnaphthalene were
      detected during growth on naphthalene, i.e. naphthyl-2-methyl-succinate and
      naphthyl-2-methylene-succinate. Additionally, all three enzymes involved in
      anaerobic degradation of 2-methylnaphthalene to 2-naphthoic acid that could be
      measured in vitro so far, i.e. naphthyl-2-methyl-succinate synthase, succinyl
      CoA:naphthyl-2-methyl-succinate CoA-transferase and naphthyl-2-methyl-succinyl
      CoA dehydrogenase were also detected in naphthalene-grown cells with similar
      activities. Induction experiments were performed to study the growth behaviour of
      the cell when transferred from naphthalene to 2-methylnaphthalene or vice versa.
      When the cells were transferred from naphthalene to 2-methylnaphthalene they grew
      immediately, indicating that no new enzymes had to be induced. On the contrary,
      the transfer of cells from 2-methylnaphthalene to naphthalene caused a lag-phase
      of almost 100 days demonstrating that an additional catabolic enzyme has to be
      activated in this case. We propose the methylation as a novel general mechanism
      of activation reactions in anaerobic degradation of unsubstituted aromatic
      hydrocarbons.

PMID- 16423021
TI  - Origin of replication in circular prokaryotic chromosomes.
AB  - To predict origins of replication in prokaryotic chromosomes, we analyse the
      leading and lagging strands of 200 chromosomes for differences in oligomer
      composition and show that these correlate strongly with taxonomic grouping,
      lifestyle and molecular details of the replication process. While all bacteria
      have a preference for Gs over Cs on the leading strand, we discover that the
      direction of the A/T skew is determined by the polymerase-alpha subunit that
      replicates the leading strand. The strength of the strand bias varies greatly
      between both phyla and environments and appears to correlate with growth rate.
      Finally we observe much greater diversity of skew among archaea than among
      bacteria. We have developed a program that accurately locates the origins of
      replication by measuring the differences between leading and lagging strand of
      all oligonucleotides up to 8 bp in length. The program and results for all
      publicly available genomes are available from
      http://www.cbs.dtu.dk/services/GenomeAtlas/suppl/origin.

PMID- 16423022
TI  - Reduction of Prussian Blue by the two iron-reducing microorganisms Geobacter
      metallireducens and Shewanella alga.
AB  - Cyanide or cyanide-metal complexes are frequent contaminants of soil or aquifers
      at industrial sites, which can be released from such sites by outgassing or
      transport with the groundwater. They form very stable complexes with iron, which
      may occur in the subsurface as an insoluble blue mineral, the so-called Prussian
      Blue (Fe(4)[Fe(CN)(6)](3)). In this study, we show that the insoluble and
      colloidal Fe(III)-cyanide complex Prussian Blue can be reduced and utilized as
      electron acceptor by the dissimilatory iron-reducing bacteria Geobacter
      metallireducens and Shewanella alga strain BrY. The microbial reduction of the
      dark blue pigment Prussian Blue leads to the formation of a completely colourless
      solid mineral, presumably Prussian White (Fe(2)[Fe(CN)(6)]), which could be
      reoxidized through exposure to air, regaining the dark blue colour. In addition,
      the microorganisms were able to grow with Prussian Blue, using it as the sole
      electron acceptor. Geobacter metallireducens could also reduce Prussian Blue
      coatings on sand, which was sampled from a contaminated site.

PMID- 16423025
TI  - Reducing the bias of probing depth and attachment level estimates using random
      partial-mouth recording.
AB  - OBJECTIVES: To evaluate the bias and precision of probing depth (PD) and clinical
      attachment level (CAL) estimates of random and fixed partial examination methods
      compared with full-mouth examinations. METHODS: PD and CAL were calculated on six
      sites for up to 28 teeth (considered to be the gold standard with no bias) and
      three fixed-site selection methods (FSSMs) that resulted in a partial examination
      of sites: the Ramfjord method, and the NIDCR methods used in NHANES I, and NHANES
      2000. Finally, seven random-site selection methods (RSSMs) were created by
      sampling the following number of sites: 84, 42, 36, 28, 20, 15, 10 and 6. To
      compare bias and precision of the methods we calculated percent relative bias and
      relative error. RESULTS: Estimates of means, standard deviations (SD), relative
      bias and relative error for RSSMs were almost identical to the full-mouth
      examination, but SDs increase slightly when fewer than 28 sites were sampled and
      relative bias and error increase for methods sampling fewer than 20 sites. The
      FSSMs had very low relative error, but much higher relative bias indicating
      underestimation. The FSSM with the smallest bias and error was the Ramfjord
      method, but the Random 36 method had less bias and less relative error. The
      NHANES 2000 method was the FSSM with the lowest bias and relative error for
      estimates of Extent Scores (percent of sites > or =3, 4, 5, or 5 mm PD or CAL)
      but random methods sampling fewer sites performed just as well. Both FSSMs and
      RSSMs underestimated prevalence, especially prevalence of less frequently
      occurring conditions, but most RSSMs were less likely to underestimate prevalence
      than the FSSMs. CONCLUSION: The promise of reducing bias and increasing precision
      of the estimates support the continued development and examination of RSSMs.

PMID- 16423026
TI  - Evaluating oral health promotion: need for quality outcome measures.
AB  - Oral health promotion effectiveness reviews have identified the need to improve
      the quality of the evaluation of interventions. A project was undertaken to
      identify and assess the quality of available outcome measures. This paper
      describes the methodology adopted and highlights the need for further development
      of oral health promotion outcome measures. Initially a thorough and comprehensive
      search of both the published and unpublished literature was undertaken to
      identify potential outcome measures. A set of quality criteria was then developed
      and used to assess the identified measures. The search identified a total of 1202
      outcome measures of which 39% (n = 466) were developed for use with
      schoolchildren. A high proportion of the identified measures were classified as
      health literacy and healthy lifestyle outcomes, appropriate for the evaluation of
      oral health education activities. Only 1% (n = 12) of measures identified were
      classified in the healthy public policy category. When reviewed against the
      quality criteria, 49% (n = 594) of the measures were considered satisfactory. The
      poorest performing measures were those classified as healthy lifestyle and health
      literacy measures in which only 33% (n = 72) and 41% (n = 240), respectively,
      were deemed to be of satisfactory quality. In conclusion, a significant number of
      oral health promotion evaluation outcome measures have been identified although
      their quality is highly variable. Very few high-quality outcome measures exist
      for use in the evaluation of oral health policy and environmental interventions.
      The lack of appropriate and high-quality outcome measures is hampering the
      development of oral health promotion.

PMID- 16423027
TI  - An empirically derived population-response model of the short form of the Oral
      Health Impact Profile.
AB  - OBJECTIVE: The aim of this paper was to model the consequences of dental
      conditions from an empirical basis and to test the model's ability to predict
      response combinations. METHODS: The model was derived from responses to the short
      form Oral Health Impact Profile (OHIP14) obtained from a UK population sample of
      5281 dentate adults. This model was then used to predict OHIP14 response
      combinations obtained from a sample of 3973 dentate and edentulous adults in
      Australia. FINDINGS: The empirically derived population-response model accounted
      for over 98% of response combinations of Australian dentate adults. CONCLUSIONS:
      The empirically derived model followed a similar hierarchical pattern to the base
      model underlying the long-form version of the measure (thereby supporting the
      validity of the OHIP14 measure) and was strongly predictive of the pattern of
      responses obtained from Australian adults.

PMID- 16423028
TI  - Pattern and severity of early childhood caries.
AB  - OBJECTIVES: The aim of this study was to investigate the association between
      selected social and behavioural variables and the pattern and severity of early
      childhood caries (ECC) within a community child population. METHODS: A cross
      sectional sample of 2515 children aged 4-5 years were examined in a preschool
      setting using decayed, missing, filled teeth/surface (dmft/dmfs) indices and a
      self-administered questionnaire was used to obtain information regarding social,
      demographic, birth, infant feeding, oral and general health attitudes. Children
      with caries (847) were divided into anterior or posterior caries pattern groups
      and severe (dmfs score > or =6) or non-severe (dmfs score <6) caries groups. The
      data were analysed using a chi-square test and modelled using a logistic
      regression procedure. RESULTS: Significant variables associated with anterior ECC
      pattern were ethnicity other than Caucasian (OR = 2.1, 95% CI = 1.4-3.1), sipping
      from the bottle during the day (OR = 1.9, 95% CI = 1.3-2.7), male gender (OR =
      1.6, 95% CI = 1.2-2.2) and sleeping with a bottle at night (OR = 1.5, 95% CI =
      1.1-2.2). Significant variables associated with severe ECC form were sipping from
      the bottle during the day (OR = 2, 95% CI = 1.4-2.8), maternal age at birth < or
      =24 years (OR = 1.8, 95% CI = 1.3-2.7), ethnicity other than Caucasian (OR = 1.6,
      95% CI = 1.1-2.5) and sleeping with a bottle at night (OR = 1.5, 95% CI = 1.1
      2.2). CONCLUSIONS: Infant bottle-feeding habits (either allowing a child to sip
      from a bottle during the day or put to sleep at night) and ethnicity other than
      Caucasian were significant determinants for both anterior caries pattern and
      severity of ECC in 4-5-year-old Australian children.

PMID- 16423030
TI  - Inter-examiner reliability in the clinical examination of temporomandibular
      disorders: influence of age.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of the age of
      the subject on inter-examiner reliability of the clinical signs of
      temporomandibular disorder (TMD). METHODS: Forty-three elderly (ES) and 44
      younger adults (YS) were selected. The female/male distribution was almost the
      same in the two groups. All participants underwent clinical examination according
      to the Research Diagnostic Criteria for TMD, performed successively by two
      clinicians. RESULTS: For metric measurements - with the exception of unassisted
      opening - the ES gave a significantly lower range of motion with both examiners
      and significantly worse percentage agreement between the examiners. A remarkable
      inter-examiner disagreement in the elderly was found with laterotrusion and
      protrusion movements. The prevalence of joint sounds was rated inconsistently by
      the examiners. The reliability of detection was not different in the two groups.
      The prevalence of tender muscle sites was also inconsistent. The overall
      percentage agreement for subjects with at least one tender muscle point was not
      age dependent. Because of the very low prevalence in ES, further statistical
      assessment of reliability is not possible. CONCLUSIONS: The age-dependent lower
      range of motion and the inferior reliability of metric measurements in the
      elderly could lead to wrong diagnoses. The reliability of detecting joint sounds
      and tender muscles was not age dependent within the limitations of the study.

PMID- 16423029
TI  - A field trial of resin-based and glass-ionomer fissure sealants: clinical and
      radiographic assessment of caries.
AB  - OBJECTIVE: The purpose of the present study was to provide further data for
      comparison of retention and caries-preventive effect of a resin-based sealant
      (Delton, and a glass-ionomer sealant (Fuji III). METHODS: The study was conducted
      in the municipality of Vaerlose located 15 km north of Copenhagen, Denmark in the
      period 1996-2001. The study comprised 153 children aged 8-13 years with a total
      of 364 site-pairs. Caries was diagnosed both clinically and radiographically, and
      sealant retention was diagnosed clinically. Sealants were placed either by one of
      four dentists, who had the responsibility for the children's dental care, by a
      dental hygienist or a dental assistant. Mean follow-up time was 38-39 months for
      sites on first permanent molars and 28-29 months for sites on second permanent
      molars. RESULTS: The retention rates were consistently, and considerably lower
      for Fuji III than for Delton. Relative risks of caries in Delton-sealed teeth
      over Fuji III-sealed teeth was 0.435 (95% CI 0.150-0.846) based on the clinical
      diagnosis, and 0.559 (95% CI 0.342-0.905) based on the radiographic diagnosis.
      The ratio of the relative risks (clinical over radiographic diagnosis) was close
      to 1 (0.778; 95% CI 0.272-1.481). CONCLUSION: In the present study, Delton-sealed
      teeth had a lower risk than Fuji III-sealed teeth of developing caries,
      independent of the caries diagnostic method used.

PMID- 16423031
TI  - Dental Discomfort Questionnaire: assessment of dental discomfort and/or pain in
      very young children.
AB  - OBJECTIVE: To present and analyse the Dental Discomfort Questionnaire (DDQ) for
      very young children and to assess the possible differences in pain-related
      behaviours displayed by children with or without reported toothache, and by
      children with or without decayed teeth. METHODS: Based on parental interviews of
      toddlers referred to a dental care practice 12 pain-related behaviours were
      identified which formed the DDQ. The DDQ was filled out by parents on behalf of
      their children (n = 146; mean age 47 months). Two-third (n = 94) of the children
      were referred to a special dental care centre and one-third (n = 52) were
      controls from a day care centre. RESULTS: The results show that the 12 items of
      the DDQ seem to measure one dimension. However, four items do not correlate with
      the presence of reported toothache, when these items are removed the DDQ-8 has a
      satisfactory reliability. All eight behaviours from the DDQ-8 occur significantly
      more often in children with decayed teeth and toothache than in children without
      decayed teeth or toothache. Especially behaviours concerning eating or brushing
      teeth are found to be more often present in children with decayed teeth and
      toothache. CONCLUSIONS: It seems useful to take the child behaviour into account
      in assessing toothache. The DDQ has shown to be a reliable instrument, which
      could be helpful in the future for both parents and dentists in identifying
      toothache in young children.

PMID- 16423032
TI  - Assessing oral health-related quality of life in general dental practice in
      Scotland: validation of the OHIP-14.
AB  - OBJECTIVES: To validate the Oral Health Impact Profile (OHIP)-14 in a sample of
      patients attending general dental practice. METHODS: Patients with pathology-free
      impacted wisdom teeth were recruited from six general dental practices in
      Tayside, Scotland, and followed for a year to assess the development of problems
      related to impaction. The OHIP-14 was completed at baseline and at 1-year follow
      up, and analysed using three different scoring methods: a summary score, a
      weighted and standardized score and the total number of problems reported.
      Instrument reliability was measured by assessing internal consistency and test
      retest reliability. Construct validity was assessed using a number of variables.
      Linear regression was then used to model the relationship between OHIP-14 and all
      significantly correlated variables. Responsiveness was measured using the
      standardized response mean (SRM). Adjusted R(2)s and SRMs were calculated for
      each of the three scoring methods. Estimates for the differences between adjusted
      R(2)s and the differences between SRMs were obtained with 95% confidence
      intervals. RESULTS: A total of 278 and 169 patients completed the questionnaire
      at baseline and follow-up, respectively. Reliability - Cronbach's alpha
      coefficients ranged from 0.30 to 0.75. Alpha coefficients for all 14 items were
      0.88 and 0.87 for baseline and follow-up, respectively. Test-retest coefficients
      ranged from 0.72 to 0.78. Validity - OHIP-14 scores were significantly correlated
      with number of teeth, education, main activity, the use of mouthwash, frequency
      of seeing a dentist, the reason for the last dental appointment, smoking, alcohol
      intake, pain and symptoms. Adjusted R(2)s ranged from 0.123 to 0.202 and there
      were no statistically significant differences between those for the three
      different scoring methods. Responsiveness - The SRMs ranged from 0.37 to 0.56 and
      there was a statistically significant difference between the summary scores
      method and the total number of problems method for symptomatic patients.
      CONCLUSIONS: The OHIP-14 is a valid and reliable measure of oral health-related
      quality of life in general dental practice and is responsive to third molar
      clinical change. The summary score method demonstrated performance as good as, or
      better than, the other methods studied.

PMID- 16423033
TI  - Caries and fluorosis in 6- and 9-year-old children residing in three communities
      in Iran.
AB  - OBJECTIVES: The aim of this study was to investigate the caries and fluorosis
      prevalence among 6- and 9-year-old students in three communities in Iran with
      varying urbanization and fluoride in piped water. METHODS: Data were obtained
      from 523 dental examinations of 6- and 9-year olds in an upper middle class
      district in Teheran (T) (0.3 mg F/l), the city of Semnan (S) (1.3 mg F/l), and
      the village Dibaj (D) (0.2 mg F/l). RESULTS: Children in the naturally
      fluoridated town showed slightly higher dmfs/dfs (SD) values for both 6-year olds
      [S: 9.1 (9.2), T: 7.2 (7.4), D: 7.1 (6.1)] and 9-year olds [S: 6.0 (6.2), T: 4.4
      (4.2), D: 5.0 (4.7)], whereas the mean dmft/dft values as well as the numbers of
      caries-free children were comparable. A lower prevalence of dental restorations
      was reported for both Semnan and Dibaj compared with Teheran. A higher prevalence
      of fluorosis [Tooth Surface Index of Dental Fluorosis (TSIF) 3-7] was observed in
      the naturally fluoridated town compared with the low-fluoridated communities.
      CONCLUSIONS: The ingestion of naturally fluoridated water (1.3 mg F/l) seemed to
      have a negligible effect on caries prevalence, but resulted in higher prevalence
      of dental fluorosis. It is emphasized that the study population was not adjusted
      for socioeconomic status, availability of dental care nor for exposures to other
      sources of fluoride. Nevertheless, it can be concluded that caries prevalence in
      Iran is quite low compared with that in other countries in the Middle East and
      that the elevated fluoride levels in the drinking water in Semnan may contribute
      to the development of mild to severe fluorosis.

PMID- 16423034
TI  - Evaluating the role of dental behaviour in oral health inequalities.
AB  - OBJECTIVE: The aim of this study was to describe differences in dental attendance
      and dental self-care behaviour between socioeconomic groups and to investigate
      the extent to which the socioeconomic gradient in oral health was explained by
      these behaviours. METHODS: We used data from a representative sample of adults in
      Australia, surveyed by telephone interview and by self-complete questionnaire.
      The dependent variables were self-reported missing teeth and the social impact of
      oral conditions evaluated with the 14-item Oral Health Impact Profile (OHIP-14).
      Socioeconomic position was measured at the small-area level. We conducted
      bivariate analysis using one-way analysis of variance and 95% confidence
      intervals (95% CI) and adjusted for the effect of age. After adjusting for age,
      dental behavioural variables were entered individually into multivariate linear
      regression models. RESULTS: Data were obtained for 3678 dentate adults aged 18-91
      years. Missing teeth and OHIP-14 scores followed a social gradient with poorer
      adults experiencing poorer outcomes. Routine dental attendance and diligent
      dental self-care were associated with inverse monotonic gradients in missing
      teeth (P < 0.05) and OHIP-14 scores (P < 0.05). Although adults living in areas
      with the least disadvantage had a preventive dental attendance orientation, no
      socioeconomic pattern was found for dental self-care. In multivariate analysis,
      the slope of the socioeconomic gradient [beta estimate for Index of Relative
      Socioeconomic Disadvantage (IRSD)] in missing teeth was not significantly
      attenuated by either dental attendance or dental self-care. For OHIP-14 scores,
      the slope of the socioeconomic gradient was significantly attenuated by dental
      visiting, but not by dental self-care and not by the combined effect of both
      behaviours. CONCLUSION: The commonly held view that the poor oral health of poor
      people is explained by personal neglect was not supported in this study.

PMID- 16423035
TI  - Putting the natural killer cell in its place.
AB  - Natural killer (NK) cells were originally described as 'null' lymphocytes, but we
      have increasing evidence of their role in recognizing pathogen, and our knowledge
      of NK cell receptors continues to expand exponentially. Human NK cells have many
      receptors for human leucocyte antigen (HLA) class I. These killer immunoglobulin
      like receptors (KIRs) and CD94/NKG2 receptors can signal in both positive and
      negative ways to regulate NK cell functions. The inhibitory receptors are the
      best characterized, but even in these cases much of their functional biology
      remains elusive. In this review, some recent advances in terms of the three
      immunoglobulin (3Ig)-domain KIRs are discussed. Natural cytotoxicity receptors
      (NCRs) are among the activatory receptors found on NK cells. While pathogen
      ligands for these receptors have been described, endogenous ligands remain
      elusive. NCRs and NKG2D, a receptor for stress-induced antigens, appear to play
      complementary functional roles in terms of NK cell activation. More recently
      described on NK cells are the Toll-like receptors. In particular, these receptors
      of the innate immune system allow NK cells to directly sense pathogen, and their
      ligation on accessory cells indirectly activates NK cells through cytokine
      production. It is becoming clear that none of these receptor systems functions in
      isolation and that it is the sum of the signals (which will reflect the
      pathogenic situation), in addition to the cytokine milieu, that will direct NK
      cell activation. The resulting cytotoxicity, cytokine production and direct cell
      cell regulatory interactions with other cells of the immune system, for example
      dendritic cells, ultimately determine the role of the NK cell in the context of
      an overall immune response.

PMID- 16423036
TI  - Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human
      corneal epithelial cells.
AB  - The objective of this study was to examine the expression of Toll-like receptor 3
      (TLR3) by human corneal epithelial cells (HCECs) and to determine whether
      exposure to the TLR3 agonist polyinosinic-polycytidylic acid [poly(I:C)] induces
      an antiviral response in these cells. Fluorescence-activated cell sorter (FACS)
      analysis revealed TLR3 to be constitutively expressed and distributed
      intracellularly in HCECs. Stimulation of HCECs with the TLR3 agonist poly(I:C)
      induced the activation of nuclear factor (NF)-kappaB and production of the
      proinflammatory cytokine interleukin (IL)-6 and the chemokine IL-8. Upon exposure
      to poly(I:C), HCECs initiated a potent antiviral response resulting in an
      increase of interferon (IFN)-beta mRNA expression (7-fold). Poly(I:C) stimulation
      also up-regulated mRNA expression of the antiviral chemokine IFN-gamma inducible
      protein 10 (IP10), myxovirus resistance gene A and 2',5'-oligoadenylate
      synthetase (5-, 10- and 9-fold, respectively), and secretion of IP10. These
      responses were also induced by exogenously added type 1 IFNs, but could not be
      blocked by pretreatment of the cells with anti-TLR3 monoclonal antibody,
      suggesting that the receptor was not expressed on the cell surface. Furthermore,
      incubation of HCECs with an endosomal acidification inhibitor, chloroquine,
      markedly inhibited poly(I:C)-mediated IFN-beta expression in HCECs. These results
      suggest that corneal epithelial cells are important sentinels of the corneal
      innate immune system against viral infection, and that stimulation of TLR3 can
      induce the expression of key proinflammatory cytokines and chemokines and
      antiviral genes that help in the defence of the cornea against viral infection.

PMID- 16423037
TI  - The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23
      functions and abrogates IL-23-mediated antitumour effects.
AB  - Interleukin (IL)-23 is a heterodimeric cytokine consisting of a novel p19
      molecule and the p40 subunit of IL-12. Since secreted p40 can act as an
      antagonist for IL-12, we investigated whether p40 also inhibited IL-23-mediated
      immunological functions. p40 did not induce interferon (IFN)-gamma or IL-17
      production from splenocytes but impaired IL-23-induced cytokine production by
      competitive binding to the IL-23 receptors. Furthermore, a mixed population of
      murine colon carcinoma Colon 26 cells transduced with the p40 gene and those
      transduced with the IL-23 gene developed tumours in syngenic mice, whereas the IL
      23-expressing Colon 26 cells were completely rejected. p40 also suppressed IFN
      gamma production of antigen-stimulated splenocytes and IL-23-mediated cytotoxic T
      lymphocyte activities in the mice that rejected Colon 26 cells expressing IL-23.
      p40 can thereby antagonize IL-23 and is a possible therapeutic agent for
      suppression of IL-23 functions.

PMID- 16423038
TI  - Characterization of a novel PMA-inducible pathway of interleukin-13 gene
      expression in T cells.
AB  - Although interleukin 13 (IL-13) is an important mediator of asthma and allergic
      diseases, the molecular mechanisms regulating IL-13 gene expression are not well
      understood. This study was designed to define the molecular mechanisms governing
      IL-13 gene expression in T cells. IL-13 expression was examined in human
      peripheral blood T cells and in the EL-4 T-cell line by enzyme-linked
      immunosorbent assay and reverse-transcription polymerase chain reaction. An IL-13
      promoter deletion analysis was performed using luciferase-based reporter plasmids
      transiently transfected into EL-4 cells by electroporation. DNA binding factors
      were investigated using electrophoretic mobility shift assays. In contrast to IL
      4 expression, which required concomitant activation of calcium- and protein
      kinase C- (PKC-) dependent signalling pathways, PKC activation alone was
      sufficient for IL-13 protein secretion in mitogen-primed (but not resting)
      peripheral blood T cells, and for IL-13 mRNA expression and promoter activity in
      EL-4 T cells. Promoter deletion analysis localized a phorbol 12-myristate 13
      acetate (PMA)-sensitive element to a proximal promoter region between -109 and 
      79 base pairs upstream from the IL-13 transcription start site. This promoter
      region supported the binding of both constitutive and PMA-inducible nuclear
      factors in gel shift assays.

PMID- 16423039
TI  - Induction of interferon-gamma from natural killer cells by immunostimulatory CpG
      DNA is mediated through plasmacytoid-dendritic-cell-produced interferon-alpha and
      tumour necrosis factor-alpha.
AB  - Immunostimulatory sequences (ISS) that contain CpG motifs have been demonstrated
      to exert antipathogen and antitumour immunity in animal models through several
      mechanisms, including the activation of natural killer (NK) cells to secrete
      interferon-gamma (IFN-gamma) and to exert lytic activity. Since NK cells lack the
      ISS receptor TLR9, the exact pathway by which NK cells are activated by ISS is
      unclear. We determined that ISS-induced IFN-gamma from NK cells is primarily
      dependent upon IFN-alpha release from plasmacytoid dendritic cells (PDCs), which
      directly activates the NK cell. However, further analysis indicated that other
      PDC-released soluble factor(s) may contribute to IFN-gamma induction. Indeed,
      tumour necrosis factor-alpha (TNF-alpha) was identified as a significant
      contributor to ISS-mediated activation of NK cells and was observed to act in an
      additive fashion with IFN-alpha in the induction of IFN-gamma from NK cells and
      to up-regulate CD69 expression on NK cells. This activity of TNF-alpha, however,
      was dependent upon the presence of PDC-derived factors such as type I interferon.
      These results illustrate an important function for type I interferon in innate
      immunity, which is not only to activate effectors like NK cells directly, but
      also to prime them for enhanced activation by other factors such as TNF-alpha.

PMID- 16423041
TI  - Salmonella porins induce a sustained, lifelong specific bactericidal antibody
      memory response.
AB  - We examined the ability of porins from Salmonella enterica serovar typhi to
      induce a long-term antibody response in BALB/c mice. These porins triggered a
      strong lifelong production of immunoglobulin G (IgG) antibody in the absence of
      exogenous adjuvant. Analysis of the IgG subclasses produced during this antibody
      response revealed the presence of the subclasses IgG2b, IgG1, IgG2a and weak
      IgG3. Despite the high homology of porins, the long-lasting anti-S. typhi porin
      sera did not cross-react with S. typhimurium. Notably, the antiporin sera showed
      a sustained lifelong bactericidal-binding activity to the wild-type S. typhi
      strain, whereas porin-specific antibody titres measured by enzyme-linked
      immunosorbent assay (ELISA) decreased with time. Because our porin preparations
      contained the outer membrane proteins C and F (OmpC and OmpF), we evaluated the
      individual contribution of each porin to the long-lasting antibody response. OmpC
      and OmpF induced long-lasting antibody titres, measured by ELISA, which were
      sustained for 300 days. In contrast, although OmpC induced sustained high
      bactericidal antibody titres for 300 days, postimmunization, the bactericidal
      antibody titre induced by OmpF was not detected at day 180. These results
      indicate that OmpC is the main protein responsible for the antibody-mediated
      memory bactericidal response induced by porins. Taken together, our results show
      that porins are strong immunogens that confer lifelong specific bactericidal
      antibody responses in the absence of added adjuvant.

PMID- 16423040
TI  - Augmented induction of CD8+ cytotoxic T-cell response and antitumour resistance
      by T helper type 1-inducing peptide.
AB  - The effector CD8(+) T cells recognize major histocompatibility complex (MHC)
      class I binding altered self-peptides expressed in tumour cells. Although the
      requirement for CD4(+) T helper type 1 (Th1) cells in regulating CD8(+) T cells
      has been documented, their target epitopes and functional impact in antitumour
      responses remain unclear. We examined whether a potent immunogenic peptide of
      Mycobacterium tuberculosis eliciting Th1 immunity contributes to the generation
      of CD8(+) T cells and to protective antitumour immune responses to unrelated
      tumour-specific antigens. Peptide-25, a major Th epitope of Ag85B from M.
      tuberculosis preferentially induced CD4(+) Th1 cells in C57BL/6 mice and had an
      augmenting effect on Th1 generation for coimmunized unrelated antigenic peptides.
      Coimmunization of mice with Peptide-25 and ovalbumin (OVA) or Peptide-25 and B16
      melanoma peptide [tyrosinase-related protein-2 (TRP-2)] for MHC class I led to a
      profound increase in CD8(+) T cells specific for OVA and TRP-2 peptides,
      respectively. This heightened response depended on Peptide-25-specific CD4(+) T
      cells and interferon-gamma-producing T cells. In tumour protection assays,
      immunization with Peptide-25 and OVA resulted in the enhancement of CD8(+)
      cytotoxic cell generation specific for OVA and the growth inhibition of EL-4
      thymoma expressing OVA peptide leading to the tumour rejection. These phenomena
      were not achieved by immunization with OVA alone. Peptide-25-reactive Th1 cells
      counteractivated dendritic cells in the presence of Peptide-25 leading them to
      activate and present OVA peptide to CD8(+) cytotoxic T cells.

PMID- 16423042
TI  - CD2 activation of human lamina propria lymphocytes reduces CD3 responsiveness.
AB  - Lamina propria lymphocytes (LPLs) are thought to be antigen-activated memory T
      cells. Yet, they respond better to ligation of the CD2 receptor than the CD3
      receptor by mitogenic antibodies. This study defines their constitutive state of
      activation and relates it to their CD3 hyporesponsiveness. The activated state of
      LPLs was demonstrated by their heightened display of the activated CD2 epitope,
      T11(3). Constitutive CD2 activation was shown by the reduction in spontaneous
      proliferation when the CD2-CD58 interaction was blocked. LPLs preferentially
      recognized CD58 rather than the major histocompatibility complex molecules on
      monocytes, triggering proliferation and interferon-gamma (IFN-gamma) secretion
      that was inhibited by blocking the CD2-CD58 interaction. To determine whether CD2
      activation of LPLs contributes to their CD3 hyporesponsiveness, they were first
      stimulated with mitogenic CD2 antibodies and then tested for CD3-induced
      proliferation. The responses were greatly reduced by prior CD2 stimulation
      compared with LPLs cultured in medium alone. This effect was not caused by
      apoptosis or by changes in CD3 expression induced by CD2 triggering. This study
      shows that LPLs are constitutively activated through CD2, that they
      preferentially recognize CD58 on monocytes and that CD2 stimulation leads to CD3
      hyporesponsiveness.

PMID- 16423044
TI  - Interleukin-16 inhibits interleukin-13 production by allergen-stimulated blood
      mononuclear cells.
AB  - Expression of interleukin (IL)-16 is increased in bronchial mucosal biopsies of
      atopic asthmatics compared to normal controls. The functional significance of
      increased expression of IL-16 at sites of allergic inflammation is not yet clear.
      We have previously shown that IL-16 inhibits IL-5 secretion by allergen
      stimulated peripheral blood mononuclear cells (PBMC). We investigated whether IL
      16 inhibits the production of other T helper 2 cytokines, namely IL-13 and IL-4,
      by allergen-specific T cells. PBMC from ragweed-sensitive atopic subjects were
      stimulated with allergen extract for cytokine production in the presence or
      absence of rhIL-16. Production of cytokines was assessed by enzyme-linked
      immunosorbent assay and reverse transcription-polymerase chain reaction. To
      evaluate whether the modulatory effect of IL-16 on cytokine synthesis was
      mediated by interferon-gamma (IFN-gamma), IL-10, IL-12 or IL-18, allergen
      stimulated PBMC were cultured in presence of IL-16 and neutralizing
      concentrations of relevant antibodies. Allergen-stimulated PBMC produced
      significantly elevated levels of IL-13 (90-740 pg/ml) as compared to unstimulated
      PBMC (0-375 pg/ml, P < 0.01). Addition of rhIL-16 resulted in down-regulation of
      IL-13 mRNA expression as well as significantly reduced amounts of IL-13 released
      by allergen-stimulated PBMC (0-457 pg/ml, P < 0.001), as observed for IL-5. No
      effect of IL-16 was observed on IL-4 mRNA expression. Treatment with IL-16
      resulted in increased levels of IL-10 and IL-18 in allergen-stimulated cell
      culture. Neutralization of IFN-gamma, IL-12, IL-10 or IL-18 did not alter the
      inhibitory effects of IL-16 on IL-13 and IL-5 secretion by allergen-stimulated
      PBMC. IL-16 did not modify IL-13 synthesis by anti-CD3-stimulated CD4(+) T cells,
      but it significantly reduced the production of IL-5. These data suggest that IL
      16 may play an important immunoregulatory role in allergic states in response to
      allergen.

PMID- 16423043
TI  - Enhanced and prolonged cross-presentation following endosomal escape of exogenous
      antigens encapsulated in biodegradable nanoparticles.
AB  - CD8(+) T-cell responses are critical in the immunological control of tumours and
      infectious diseases. To prime CD8(+) T cells against these cell-associated
      antigens, exogenous antigens must be cross-presented by professional antigen
      presenting cells (APCs). While cross-presentation of soluble antigens by
      dendritic cells is detectable in vivo, the efficiency is low, limiting the
      clinical utility of protein-based vaccinations. To enhance the efficiency of
      presentation, we generated nanoparticles from a biodegradable polymer, poly(D,L
      lactide-co-glycolide) (PLGA), to deliver antigen into the major
      histocompatibility complex (MHC) class I antigen presentation pathway. In primary
      mouse bone marrow-derived dendritic cells (BMDCs), the MHC class I presentation
      of PLGA-encapsulated ovalbumin (OVA) stimulated T cell interleukin-2 secretion at
      1000-fold lower concentration than soluble antigen and 10-fold lower than antigen
      coated latex beads. The microparticles also served as an intracellular antigen
      reservoir, leading to sustained MHC class I presentation of OVA for 72 hr,
      decreasing by only 20% after 96 hr, a time at which the presentation of soluble
      and latex bead-associated antigens was undetectable. Cytosol extraction
      demonstrated that antigen delivery via PLGA particles increased the amount of
      protein that escaped from endosomes into the cytoplasm, thereby increasing the
      access of exogenous antigen to the classic MHC class I loading pathway. These
      data indicate that the unique properties of PLGA particle-mediated antigen
      delivery dramatically enhance and sustain exogenous antigen presentation by MHC
      class I, potentially facilitating the clinical use of these particles in
      vaccination.

PMID- 16423045
TI  - The delivery of an antigen from the endocytic compartment into the cytosol for
      cross-presentation is restricted to early immature dendritic cells.
AB  - Dendritic cells (DCs) are the only antigen-presenting cell population having a
      cross-presentation capacity. For cross-presentation, however, the intracellular
      antigen-processing pathway and its regulatory mechanism have not been defined.
      Here we report the differences in cross-presentation ability among murine bone
      marrow-derived immature DC, early immature day8-DC and late immature day10-DC,
      and fully mature day10 + lipopolysaccharide DC. Day8-DCs and day10-DCs show an
      immature phenotypic profile but are different in morphology. Day8-DCs can
      internalize an abundant volume of exogenous soluble ovalbumin (OVA) and result in
      cross-presentation. In contrast, day10-DCs are not able to cross-present,
      although they maintain efficient macropinocytosis. Exogenously internalized OVA
      antigens are stored in the endocytic compartments. The endocytic compartments are
      temporarily maintained at mildly acidic pH in day8-DCs and are rapidly acidified
      in day10-DCs after uptake of antigens. We show that OVA antigens accumulated in
      the endocytic compartments move into the cytosol in day8-DCs but do not in day10
      DCs. NH(4)Cl-treatment, which neutralizes the acidic endocytic compartments
      and/or delays endosomal maturation, restores day10-DCs for transport the stored
      OVA antigens from the endocytic compartments into the cytosol.
      Diphenyleneiodonium chloride-treatment, which acidifies the endocytic
      compartments, decreases an amount of transported OVA antigen into the cytosol in
      day8-DCs. These data indicate that only the early immature stage of DC interferes
      with endosomal maturation, even after uptake of exogenous antigens, and then
      transports the antigens into the cytosol.

PMID- 16423047
TI  - Rapid and preferential distribution of blood-borne alphaCD3epsilonAb to the liver
      is followed by local stimulation of T cells and natural killer T cells.
AB  - Dissemination of soluble molecules or antigens via the blood stream is considered
      to lead to a uniform distribution in the various organs of the body, but organ
      specific microarchitecture and vascularization may influence this. Following
      intravenous injection of alphaCD3epsilon antibody (alphaCD3epsilonAb) we observed
      clear differences in antibody binding to Fcgamma receptor (FcgammaR)(+) antigen
      presenting cells (APCs) or T lymphocytes in different organs. Significant binding
      of blood-borne alphaCD3epsilonAb was only detected in the spleen and liver and
      not in the thymus or lymph node. In the spleen, only 10% of dendritic
      cells/macrophages and 40% of T-cell receptor (TCR)-beta(+) cells were positive
      for alphaCD3epsilonAb, and, dependent on FcgammaR-mediated cross-linking of
      alphaCD3epsilonAb, a similar percentage of splenic TCR-beta(+) cells were
      stimulated and became CD69(+). Stimulation of TCR-beta(+) cells in the liver was
      at least as efficient as in the spleen, but almost all T cells and all scavenger
      liver sinusoidal endothelial cells bound alphaCD3epsilonAb. In contrast to CD69
      up-regulation, only CD4(+) natural killer T (NKT) cells and CD11a(high) CD8(+) T
      cells were activated by alphaCD3epsilonAb and expressed interferon (IFN)-gamma.
      Again, IFN-gamma release from NKT/T cells was at least as efficient in the liver
      as in the spleen. Taken together, our results support the notion that the
      combination of extensive hepatic vascularization and very high scavenger activity
      allows the liver to fulfill its metabolic tasks and to promote stimulation of the
      large but widely distributed hepatic population of NKT/T cells.

PMID- 16423046
TI  - OX40 interactions in gastrointestinal nematode infection.
AB  - The immune expulsion of gastrointestinal nematode parasites is usually associated
      with T helper type 2 (Th2) responses, but the effector mechanisms directly
      responsible for parasite loss have not been elucidated. The intestinal
      inflammatory response accompanying infection with gastrointestinal helminths is
      thought to be a contributory factor leading to the expulsion of the parasite.
      However, we have shown that the intestinal inflammation, which is controlled by
      interleukin (IL)-4, is not required for parasite expulsion. OX40-OX40 ligand (L)
      signals have been shown to be important for the development of Th2 immune
      responses but are also involved in a number of inflammatory diseases including
      those of the intestine. Here, we have investigated the effect of OX40 and OX40L
      fusion protein treatment on the induction of protective Th2 responses and
      enteropathy following infection with the gastrointestinal nematode Trichinella
      spiralis. Treatment with an OX40-immunoglobulin (Ig) blocking fusion protein
      resulted in enhanced expulsion of the parasite and an increase in the
      accompanying mastocytosis, despite unaltered levels of Th2 cytokines.
      Furthermore, there was a delay in the villus atrophy and crypt hyperplasia
      usually associated with this infection. In contrast, levels of Th2 cytokines were
      greatly up-regulated in mice treated with an OX40L-Ig activating fusion protein,
      yet the expulsion of the parasite and the enteropathy were unaffected. Therefore,
      OX40 ligation potentiates the Th2 response without enhancing host protective
      immune responses, whereas blocking the OX40-OX40L interaction enhances host
      protection without promoting Th2 cytokine responses during Trichinella spiralis
      infection.

PMID- 16423048
TI  - Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int
      B220+ gammadelta T cells with double-negative CD4- CD8- phenotype in the liver.
AB  - DBA/2 (H-2(d)) mice are known to be more resistant than C57BL/6 (B6, H-2(b)) mice
      to the non-lethal 17XNL strain of Plasmodium yoelii. This is a very strange
      phenomenon because the functions of conventional T cells, especially CD8(+) T
      cells, are known to be somewhat lower in DBA/2 mice than in other strains of
      mice. We examined herein how immune responses differed between DBA/2 mice and B6
      mice during malarial infection. DBA/2 mice and (DBA/2 x B6)F(1) (BDF(1), H
      2(b/d)) mice were found to have milder parasitaemia and to recover more quickly
      from malarial infection than B6 mice. These DBA/2 and BDF(1) mice were also found
      to experience a marked expansion of interleukin (IL)-2Rbeta(+) CD3(int) cells and
      gammadelta T cells in the liver, especially in the recovery phase. The expansion
      of unconventional T cells (i.e. B220(+) T cells) was also marked in DBA/2 and
      BDF(1) mice. The majority of B220(+) T cells were gammadelta T cells and these T
      cells were double-negative CD4(-) CD8(-). More importantly, the production of
      immunoglobulin M (IgM)-type anti-DNA autoantibody was also higher in DBA/2 and
      BDF(1) mice than in B6 mice. In conjunction with data on cytokine production,
      these results indicate that primitive T and B cells, namely autoreactive
      extrathymic T cells and autoantibody-producing B cells, may be much more
      activated in DBA/2 mice and therefore resistant to the non-lethal 17XNL strain of
      P. yoelii.

PMID- 16423049
TI  - Molecular characterization of an arthritogenic collagen peptide interacting with
      I-Ar.
AB  - Collagen-induced arthritis (CIA) is an autoimmune arthritis that can be elicited
      by the immunization of genetically susceptible strains of mice with type II
      collagen (CII). We have analysed the molecular interactions that occur between an
      arthritogenic T-cell determinant CII (442-457) and the murine class II
      susceptibility allele I-A(r). To determine which amino acid residues within the
      CII (442-457) sequence are responsible for binding to I-A(r), a soluble I
      A(r):IgG2aFc fusion protein-peptide binding assay was developed. Various
      concentrations of analogue peptides were tested for their ability to compete with
      biotinylated CII (607-622) for binding to I-A(r), thereby establishing a relative
      comparison of the binding affinities among these analogues. Analogue peptides
      with substitutions at positions 447 (Ala --> Val), 448 (Gly --> Ala) and 451 (Gly
      --> Ala) bound poorly to the I-A(r) molecule. These data suggest that positions
      447, 448 and 451 on CII are the major anchor points to I-A(r) molecules. In
      cytokine assays, only substitutions within positions 445-454 decreased the
      interferon-gamma production by T cells. These data narrow the core of the
      arthritogenic T-cell determinant to CII (445-454). Identification of the
      molecular interactions involved in T-cell recognition of CII should lead to
      antigen-specific means of inhibiting autoimmune arthritis.

PMID- 16423050
TI  - CD45: all is not yet crystal clear.
AB  - CD45 has been recognized as an important player in regulating signalling in
      lymphocytes. However, compared with tyrosine kinases, phosphatases are still
      poorly understood in terms of the details of their specificity and regulation.
      Here, the recent progress in understanding the biology of the first recognized
      receptor tyrosine phosphatase, CD45, is reviewed.

PMID- 16423051
TI  - Functional and transcriptional profiling of MUTZ-3, a myeloid cell line acting as
      a model for dendritic cells.
AB  - The incidence of allergy is steadily increasing, but the molecular mechanisms
      involved in the allergic immune response are still not fully understood. In
      particular, further investigations focusing on dendritic cells, which are central
      in orchestrating the immune response, are needed. The objective of this study was
      to investigate the ability of myeloid leukaemia-derived cell lines, such as KG-1,
      THP-1 and MUTZ-3, to serve as in vitro models for dendritic cells. The ability of
      these cell lines to mature into functional dendritic cells, expressing
      costimulatory molecules, was assessed by functional and transcriptional profiling
      and compared with that of monocyte-derived dendritic cells, which are now used as
      a standard source of dendritic cells. High-density microarray analysis was
      utilized to study the transcriptional activity and kinetics of activation of the
      differentiated MUTZ-3 cell line, in response to a cocktail of inflammatory
      cytokines. The data obtained clearly demonstrate that MUTZ-3 cells have the
      ability to induce antigen-independent proliferation in CD4(+) CD45RA(+) T cells,
      whereas KG-1 and THP-1 only induced a marginal response. Furthermore, MUTZ-3
      displayed the phenotypic and transcriptional profiles of immature dendritic
      cells, after differentiation with granulocyte-macrophage colony-stimulating
      factor and interleukin-4. Upon activation with inflammatory cytokines, MUTZ-3
      matured phenotypically and exhibited a gene induction similar to that of monocyte
      derived dendritic cells. This delineation of the cellular and transcriptional
      activity of MUTZ-3, in response to maturational stimuli, demonstrates the
      significance of this cell line as a model for functional studies of inflammatory
      responses.

PMID- 16423052
TI  - Herpes simplex virus 1 infection induces the expression of proinflammatory
      cytokines, interferons and TLR7 in human corneal epithelial cells.
AB  - Herpetic epithelial and stromal keratitis is a sight-threatening ocular
      infection. To study the role of the epithelium in the innate response to herpes
      simplex virus 1 (HSV-1) infection of the cornea, we used a telomerase
      immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs
      as a model and infected the cells with HSV-1 (KOS strain). HSV-1 infection of
      HCECs resulted in a two-phase activation of nuclear factor-kappaB (NF-kappaB),
      JNK and p38, with the first peak at 1-4 hr and a second peak at 8 hr. Concomitant
      with the first peak of activation, transcriptional expression of interleukin (IL)
      6, IL-8, tumour necrosis factor (TNF)-alpha and interferon (IFN)-beta was rapidly
      induced in HSV-1-infected cells. HSV-1 infection also induced the production of
      IL-6, IL-8, and TNF-alpha in both HUCL cells and primary HCECs. Coincident with
      the second phase of NF-kappaB activation in HSV-1-infected HCECs, the expression
      of Toll-like receptor 7 (TLR7) was induced, whereas the level of TLR3 was greatly
      down-regulated. Thus, in response to HSV-1 infection, HCECs produce
      proinflammatory cytokines, leading to infiltration, and IFNs to enhance the
      antiviral activity in the cornea, probably through sequential activation of TLRs.

PMID- 16423053
TI  - A canine model of cutaneous late-phase reactions: prednisolone inhibition of
      cellular and cytokine responses.
AB  - Immunoglobulin E (IgE)-mediated late-phase reactions can be induced in atopic
      humans by intradermal injection of relevant allergens or anti-IgE antibodies. The
      histology of these reactions resembles that of naturally occurring atopic
      dermatitis. Strikingly similar responses can be induced in dogs, suggesting that
      a canine model could prove valuable for preclinical investigation of drugs
      targeting late-phase reactions. This study was designed to characterize the
      cellular, cytokine and chemokine responses after intradermal anti-IgE injection
      in untreated and prednisolone-treated dogs. Normal beagles were untreated or
      treated with prednisolone before intradermal injection of polyclonal rabbit anti
      canine IgE or normal rabbit IgG. Biopsies were taken before injection and 6, 24
      and 48 hr after injection. Samples were evaluated by histological and
      immunohistochemical staining, as well as by real-time quantitative polymerase
      chain reaction analysis. Dermal eosinophil and neutrophil numbers increased
      dramatically within 6 hr after injection of rabbit anti-canine IgE, and remained
      moderately elevated at 48 hr. The numbers of CD1c(+) and CD3(+) mononuclear cells
      were also increased at 6 hr. The real-time quantitative polymerase chain reaction
      demonstrated marked increases in mRNA expression for interleukin-13 (IL-13),
      CCL2, CCL5 and CCL17. Levels of mRNA for IL-2, IL-4, IL-6 and IFN-gamma did not
      change within the limits of detection. Prednisolone administration suppressed the
      influx of neutrophils, eosinophils, CD1c(+) and CD3(+) cells, as well as
      expression of IL-13, CCL2, CCL5 and CCL17. These data document the cytokine and
      chemokine responses to anti-IgE injection in canine skin, and they demonstrate
      the ability of the model to characterize the anti-inflammatory effects of a known
      therapeutic agent.

PMID- 16423054
TI  - A novel mechanism of nuclear factor-kappaB regulation by adenoviral protein
      14.7K.
AB  - Viruses have evolved many different ways to evade immune attacks. The adenoviral
      E3 protein 14.7K effectively inhibits antiviral immunity and inflammation.
      However, the underlying mechanism for this effect is unclear. Here we show that
      14.7K is a potent inhibitor of nuclear factor (NF)-kappaB transcriptional
      activity following Toll-like receptor (TLR) or tumour necrosis factor (TNF)
      receptor signalling. The inhibition of the NF-kappaB activity occurs downstream
      of IkappaBalpha degradation and NF-kappaB translocation into the nucleus.
      Analysis of NF-kappaB DNA binding reveals that 14.7K specifically inhibits p50
      homodimer DNA binding and that this inhibition is mediated through the
      interaction of 14.7K with p50. We propose that 14.7K inhibits NF-kappaB activity
      through directly blocking p50 binding to DNA and that this is the basis for its
      anti-inflammatory properties. Our data also indicate a role for p50 homodimer
      dependent transcription in inflammation.

PMID- 16423055
TI  - Activated T cells express the OX40 ligand: requirements for induction and
      costimulatory function.
AB  - OX40/OX40 ligand (OX40L) interactions have been shown to exert potent
      costimulatory effects on T-cell activation. OX40 expression is transiently up
      regulated on T cells following T-cell receptor engagement, while OX40L is
      expressed on antigen-presenting cells following activation. Although expression
      of the OX40L by T cells has been reported, the requirements for induction of
      OX40L on T cells have not been studied in detail. Here, we demonstrate that the
      OX40L can be induced on murine CD4(+) and CD8(+) T cells after 6 days of culture
      under T helper type 1 (Th1) conditions, but not under Th2 conditions. Induction
      of OX40L expression required a high concentration of interleukin-12 (IL-12), was
      not seen in the presence of interferon-gamma, and was dependent on signal
      transducer and activator of transcription type 4 (STAT4). Notably, induction of
      OX40L on T cells was only seen at very low concentrations of antigen or anti-CD3.
      T-cell-expressed OX40L was fully capable of delivering a potent costimulatory
      signal that enhanced the proliferation of CD4(+) T cells as well as promoted
      their differentiation to Th2 cells. OX40L expression could also be induced on
      CD4(+) T cells in vivo following immunization with low-dose antigen and an IL-12
      inducer. OX40/OX40L interactions between antigen-specific T cells may occur in T
      cell zones in lymph node and spleen when OX40L expression has diminished on APC.
      Costimulation by T-cell-expressed OX40L may result in deviation of a Th1 response
      to a Th2 response under conditions where T cells are exposed to low
      concentrations of foreign or autoantigens in the presence of high concentrations
      of IL-12.

PMID- 16423056
TI  - Differential regulation of neutrophil chemotaxis to IL-8 and fMLP by GM-CSF: lack
      of direct effect of oestradiol.
AB  - Neutrophils are a normal constituent of the female reproductive tract and their
      numbers increase in the late secretory phase of the menstrual cycle prior to
      menses. Several cytokines are produced in female reproductive tract tissue. In
      particular granulocyte-macrophage colony-stimulating factor (GM-CSF), a potent
      activator of neutrophils, is secreted in high concentrations by female
      reproductive tract epithelia. We previously observed that GM-CSF synergizes
      strongly with interleukin-8 (IL-8) in enhancing chemotaxis of neutrophils. Thus
      we investigated whether pretreatment of neutrophils with GM-CSF would prime
      subsequent chemotaxis to IL-8 in the absence of GM-CSF. Surprisingly, a 3-hr
      pulse of GM-CSF severely diminished chemotaxis to IL-8, whereas N-formyl-methyl
      leucyl-phenylalanine (fMLP)-mediated chemotaxis was retained. Conversely, when
      cells were incubated without GM-CSF they retained IL-8-mediated migration but
      lost fMLP chemotaxis. These changes in chemotaxis did not correlate with
      expression of CXCR1, CXCR2 or formyl peptide receptor. However, IL-8-mediated
      phosphorylation of p44/42 mitogen-activated protein kinase was greatly reduced in
      neutrophils that no longer migrated to IL-8, and was diminished in cells that no
      longer migrated to fMLP. Oestradiol, which is reported by some to exert an anti
      inflammatory effect on neutrophils, did not change the effects of GM-CSF. These
      data suggest that neutrophil function may be altered by cytokines such as GM-CSF
      through modulation of signalling and independently of surface receptor
      expression.

PMID- 16423057
TI  - Role of matrix metalloproteinase-7 in the modulation of a Chlamydia trachomatis
      infection.
AB  - To determine the role of matrix metalloproteinase-7 (MMP-7) in the pathogenesis
      of chlamydial infection, C57BL/6 wild-type (WT) and MMP-7 knockout (KO) mice were
      infected intravaginally with Chlamydia trachomatis mouse pneumonitis (MoPn). Over
      a period of 6 weeks postinfection, various organs were cultured for C.
      trachomatis. Other infected animals were mated to assess their fertility status.
      No significant differences were observed between WT and KO mice in the number of
      animals with positive vaginal cultures, length of time of C. trachomatis
      shedding, or the number of C. trachomatis inclusion-forming units (IFU) recovered
      from their genital tracts. Likewise, the number of animals with hydrosalpinx, and
      the fertility rates and the number of embryos per mouse, were similar in WT and
      KO mice. Cultures from the spleen, lungs, kidneys and large intestine yielded
      similar numbers of IFU from WT and KO mice. However, the number of C. trachomatis
      IFU recovered from the small intestine of KO mice was significantly higher than
      that recovered from the small intestine of WT mice at 2 weeks postinfection.
      Because MMP-7 KO mice are deficient in active intestinal alpha-defensins, the
      results suggest that these components play a role in regulating colonization of
      the gastrointestinal tract by Chlamydia. By contrast, MMP-7 is dispensable in the
      progression and resolution of the genital tract infection.

PMID- 16423058
TI  - High-risk human papilloma virus infection decreases the frequency of dendritic
      Langerhans' cells in the human female genital tract.
AB  - Dendritic cells (DC) are often arranged in planar layers in tissues with high
      antigenic exposure, such as skin and mucosae. Providing an en face view, this
      arrangement optimizes in situ analysis regarding morphology (even of individual
      dendrites), topographic distribution (regular/clustered) and quantification. The
      few reports on human genital DC usually utilize single markers and conventional
      sections, restricting immunolabelling only to cell parts sectioned by the cut. To
      better assess DC in situ, we labelled epithelial sheets, prepared from fresh
      cervix biopsies, with antibodies to major histocompatibility complex (MHC)-CII,
      CD1a and Langerin, revealing (with each of these markers) a dense DC network in a
      planar-like, regular distribution. Using the hybrid capture system to detect the
      high-risk mucotropic human papilloma virus (HPV) group, 16 positive and five
      negative women were studied and the results were compared between these groups.
      DC frequency per area was substantially reduced (to approximately 50% for the
      three markers) in samples from all HPV-infected patients compared with samples
      from controls. Unlike HPV(-) samples, Langerin(+) DC in HPV(+) cervix exhibited a
      highly accentuated dendritic appearance. We believe this to be the first study
      using these three DC-restricted markers (Langerin, CD1a and MHC-CII) in cervical
      epithelial sheets from high-risk HPV(+) donors and also the first study to
      demonstrate the morphological and quantitative changes triggered by high-risk HPV
      infection. Cervical DC reduction in early, premalignant high-risk HPV infection
      might represent viral subversion strategies interfering with efficient antigen
      handling by the immune system's peripheral sentinels, the DC, perhaps hampering
      appropriate recruitment and subsequent development of effector (cytotoxic) T
      cells.

PMID- 16423059
TI  - Antibodies neutralizing feline leukaemia virus (FeLV) in cats immunized with the
      transmembrane envelope protein p15E.
AB  - The feline leukaemia virus (FeLV) vaccines that are currently in wide use are
      generally poor inducers of virus-neutralizing antibodies, although such
      antibodies appear after recovering from challenge. However, the presence of
      neutralizing antibodies in cats recovering from natural FeLV infection clearly
      correlates with resistance to subsequent infection and passive transfer of
      antibodies can protect other animals. After demonstrating the induction of
      neutralizing antibodies in rats and goats immunized with the transmembrane
      envelope protein p15E of FeLV, cats were immunized with the same antigen. High
      titres of neutralizing antibodies specific for FeLV were induced and epitope
      mapping revealed a pattern of recognition similar to that seen following
      immunization of rats and goats. These epitopes are highly related to epitopes
      recognized after immunization with porcine endogenous retrovirus (PERV) p15E and
      to epitopes recognized by neutralizing antibodies in patients infected with human
      immunodeficiency virus type 1. The ability of p15E to induce neutralizing
      antibodies in cats suggests that it should be included in the next generation of
      vaccines. In contrast, sera from FeLV-infected animals usually fail to recognize
      the neutralization-relevant epitopes in p15E. Since homologous epitope sequences
      are present in feline endogenous retroviruses, it appears that tolerance against
      these sequences is not induced.

PMID- 16423060
TI  - Mature monocyte-derived dendritic cells respond more strongly to CCL19 than to
      CXCL12: consequences for directional migration.
AB  - The chemokine receptor CCR7 is crucial for migration of mature dendritic cells
      (DC) directed toward secondary lymphoid organs; however, there is little
      knowledge about the function of the homeostatic chemokine receptor CXCR4 in DC
      and its contribution to directional migration of DC during inflammation. By
      comparing the impact of chemokine receptor engagement on mature DC we found that
      the CCR7 ligand CCL19 holds a stronger chemotactic potency than the CXCR4 ligand
      CXCL12. Moreover, CCL19 elicited rapid, steep and long-lasting mobilization of
      intracellular calcium in individual cells and induced intense phosphorylation of
      extracellular signal-regulated kinase 1/2 and protein kinase B, while the
      intracellular signals elicited by CXCL12 were in part distinct and significantly
      weaker. Analysis of chemokine receptor expression revealed that although CCR7 and
      CXCR4 were expressed by a similar percentage of DC, the mean fluorescence
      intensity of CCR7 was up to six times higher, suggesting a higher receptor
      density. Based on these correlations we propose that the type of chemokine signal
      in conjunction with the expression and functional activity of the respective
      chemokine receptor is also determining the migration rate and potency of a
      chemotactic response in mature DC. In conclusion, our data support the
      fundamental role of CCR7 for rapidly guiding DC toward secondary lymphoid organs
      at an extra- and intracellular molecular level and on the contrary render CXCR4 a
      weaker contributor to directional migration of DC during inflammation.

PMID- 16423061
TI  - Deletion is neither sufficient nor necessary for the induction of peripheral
      tolerance in mature CD8+ T cells.
AB  - Previous reports have demonstrated clonal deletion of CD8(+) T cells during
      peripheral tolerance induction to tissue antigens. However, direct evidence
      demonstrating a causal connection between deletion and tolerance has not been
      reported because of model limitations in which the tissue antigens were expressed
      in vital organs. Thus, studies were initiated in a mouse model where expression
      of a membrane-bound ovalbumin fusion protein (mOVA) was driven by a prostate
      specific androgen regulated probasin promotor, providing restricted expression in
      a non-vital organ where antigen levels can be abrogated through androgen
      deprivation. Adoptive transfer of mOVA specific CD8(+) T cells (OT-I) was used to
      assess the development of peripheral tolerance. Proliferation of OT-I cells was
      observed, as was partial deletion of transferred OT-I cells. Although deletion
      occurred, the long-term persistence of a stable level of OT-I cells was observed.
      Importantly, the persistent OT-I cells lost antigen responsiveness within 3 weeks
      of transfer. Castration resulted in loss of high-level prostate mOVA expression,
      with a resultant abrogation of tolerance induction, but surprisingly did not
      affect the deletion rate of OT-I cells. In contrast, abrogation of deletion
      through the adoptive transfer of OT-I cells from third generation CD95-deficient
      mice had no effect on tolerance induction. These data demonstrate the necessity
      for continued expression of tissue antigen throughout the establishment of
      peripheral tolerance. Furthermore, these findings demonstrate that deletion is
      neither sufficient nor required for CD8(+) T-cell tolerance to tissue antigens,
      suggesting that regulatory events independent of deletion are necessary for
      peripheral tolerance induction to prostate antigens.

PMID- 16423062
TI  - Protection of non-obese diabetic mice from autoimmune diabetes by Escherichia
      coli heat-labile enterotoxin B subunit.
AB  - Autoimmune diabetes in the non-obese diabetic (NOD) mouse is associated with
      development of inflammation around the islets at around 4-5 weeks of age, which
      may be prolonged until frank diabetes begins to occur around 12 weeks of age.
      Although many interventions can halt disease progression if administration
      coincides with the beginning of the anti-beta cell response, very few are able to
      prevent diabetes development once insulitis is established. Here we describe a
      strategy which blocks cellular infiltration of islets and prevents diabetes.
      Intranasal treatment with the B-subunit of Escherichia coli heat labile
      enterotoxin (EtxB), a protein that binds GM1 ganglioside (as well as GD1b, asialo
      GM1 and lactosylceramide with lower affinities), protected NOD mice from
      developing diabetes in a receptor-binding dependent manner. Protection was
      associated with a significant reduction in the number of macrophages, CD4(+) T
      cells, B cells, major histocompatibility complex class II(+) cells infiltrating
      the islets. Despite this, treated mice showed increased number of interleukin
      10(+) cells in the pancreas, and a decrease in both T helper 1 (Th1) and Th2
      cytokine production in the pancreatic lymph node. Disease protection was also
      transferred with CD4(+) splenocytes from treated mice. Taken together, these
      results demonstrated that EtxB is a potent immune modulator capable of blocking
      diabetes.

PMID- 16423063
TI  - Interleukin-4 can induce interleukin-4 production in dendritic cells.
AB  - The presence of interleukin-4 (IL-4) during the generation of dendritic cells
      (DC) from precursor cells results in measurable increases of IL-12 in
      supernatants but IL-4 secretion has not been reported. However, DC have IL-4
      receptors and are able to make IL-4. We therefore sought evidence for autocrine
      effects of IL-4 on DC. IL-4 gene expression was low in DC generated from bone
      marrow stem cells in the presence of granulocyte-macrophage colony-stimulating
      factor but was up-regulated by exposure of the developing DC to IL-4. Exposure to
      IL-4 also induced intracellular IL-4 production in DC. The intracellular IL-4
      induced in the presence of IL-4 was increased following further DC maturation
      with tumour necrosis factor-alpha. By contrast, in supernatants of DC, IL-4 was
      rarely detected and only at late culture periods. However, after exposure of DC
      to IL-4, cell-bound IL-4 was detected transiently, which suggested binding and
      internalization of the cytokine. Binding via IL-4 receptor-alpha was indicated
      from phosphorylation of the signal transducer and activator of transcription
      (STAT) protein 6, which is known to mediate IL-4 function. Cytokine persisting
      within the supernatants of the cells may therefore be unrepresentative of the
      actual production and function of IL-4 in the cells; IL-4 may be produced in DC
      in response to exposure to IL-4 but may then be lost from the supernatants during
      cell binding and activation of the cells.

PMID- 16423064
TI  - Inverse correlation between CD4+ regulatory T-cell population and autoantibody
      levels in paediatric patients with systemic lupus erythematosus.
AB  - CD4(+) CD25(+) regulatory T cells (Tregs) are critical in maintaining self
      tolerance and preventing organ-specific autoimmunity. Their role in paediatric
      systemic lupus erythematosus (SLE), an autoimmune disease characterized by
      inappropriate regulation of hyperactivated B and T cells, has not been clearly
      defined. Using flow cytometry to determine cell populations and real-time
      polymerase chain reaction to assay mRNA expression for FOXP3, CTLA-4, and GITR,
      we characterized CD4(+) CD25(+) T cells in paediatric SLE patients and healthy
      subjects. The frequency of CD4(+) CD25(+) Tregs was significantly decreased in
      patients with active SLE compared with patients with inactive SLE and with
      controls (7.27% +/- 2.50%, 9.59% +/- 2.80% and 9.78% +/- 2.11%, respectively; P =
      0.027 and P < 0.001, respectively), and was inversely correlated with disease
      activity, as assessed with the Systemic Lupus Erythematosus Disease Activity
      Index 2000 scores (r = -0.59, P = 0.001) and serum anti-double-stranded DNA
      levels (r = -0.65, P < 0.001). Our preliminary investigations found elevated
      surface expression of GITR in CD4(+) CD25(+) T cells, elevated mRNA expression of
      CTLA-4 in CD4(+) T cells and higher amounts of mRNA expression for FOXP3 in
      CD4(+) cells in patients with active SLE compared with patients with inactive
      disease and controls. We demonstrated reduced CD4(+) CD25(+) Treg levels were
      inversely correlated with disease activity, indicating a defective Treg
      population in paediatric SLE patients. The differences in the expression of
      FOXP3, CTLA-4 and GITR imply the possible role of CD4(+) Tregs in the
      pathogenesis of SLE.

PMID- 16423066
TI  - Biotechnology, physiology and genetics of the yeast Pichia anomala.
AB  - The ascomycetous yeast Pichia anomala is frequently associated with food and feed
      products, either as a production organism or as a spoilage yeast. It belongs to
      the nonSaccharomyces wine yeasts and contributes to the wine aroma by the
      production of volatile compounds. The ability to grow in preserved food and feed
      environments is due to its capacity to grow under low pH, high osmotic pressure
      and low oxygen tension. A new application of P. anomala is its use as a
      biocontrol agent, which is based on the potential to inhibit a variety of moulds
      in different environments. Although classified as a biosafety class-1 organism,
      cases of P. anomala infections have been reported in immunocompromised patients.
      On the other hand, P. anomala killer toxins have a potential as antimicrobial
      agents. The yeast can use a broad range of nitrogen and phosphor sources, which
      makes it a potential agent to decrease environmental pollution by organic
      residues from agriculture. However, present knowledge of the physiological basis
      of its performance is limited. Recently, the first studies have been published
      dealing with the global regulation of the metabolism of P. anomala under
      different conditions of oxygenation.

PMID- 16423067
TI  - Molecular organization of the cell wall of Candida albicans and its relation to
      pathogenicity.
AB  - Candida albicans is one of the most important opportunistic pathogenic fungi.
      Weakening of the defense mechanisms of the host, and the ability of the
      microorganism to adapt to the environment prevailing in the host tissues, turn
      the fungus from a rather harmless saprophyte into an aggressive pathogen. The
      disease, candidiasis, ranges from light superficial infections to deep processes
      that endanger the life of the patient. In the establishment of the pathogenic
      process, the cell wall of C. albicans (as in other pathogenic fungi) plays an
      important role. It is the outer structure that protects the fungus from the host
      defense mechanisms and initiates the direct contact with the host cells by
      adhering to their surface. The wall also contains important antigens and other
      compounds that affect the homeostatic equilibrium of the host in favor of the
      parasite. In this review, we discuss our present knowledge of the structure of
      the cell wall of C. albicans, the synthesis of its different components, and the
      mechanisms involved in their organization to give rise to a coherent composite.
      Furthermore, special emphasis has been placed on two further aspects: how the
      composition and structure of C. albicans cell wall compare with those from other
      fungi, and establishing the role of some specific wall components in
      pathogenesis. From the data presented here, it becomes clear that the
      composition, structure and synthesis of the cell wall of C. albicans display both
      subtle and important differences with the wall of different saprophytic fungi,
      and that some of these differences are of utmost importance for its pathogenic
      behavior.

PMID- 16423068
TI  - Occurrence and function of yeasts in Asian indigenous fermented foods.
AB  - In the Asian region, indigenous fermented foods are important in daily life. In
      many of these foods, yeasts are predominant and functional during the
      fermentation. The diversity of foods in which yeasts predominate ranges from
      leavened bread-like products such as nan and idli, to alcoholic beverages such as
      rice and palm wines, and condiments such as papads and soy sauce. Although
      several products are obtained by natural fermentation, the use of traditional
      starter cultures is widespread. This minireview focuses on the diversity and
      functionality of yeasts in these products, and on opportunities for research and
      development.

PMID- 16423069
TI  - Metabolic pathway engineering for complex polyketide biosynthesis in
      Saccharomyces cerevisiae.
AB  - Polyketides are a diverse group of natural products with significance in human
      and veterinary medicine. Because polyketides are structurally complex molecules
      and fermentation is the most commercially viable route of production, a generic
      heterologous host system for high-level polyketide production is desirable.
      Saccharomyces cerevisiae has been shown to be an excellent production host for a
      simple polyketide, yielding 1.7 g of 6-methylsalicylic acid per liter of culture
      in un-optimized shake-flask fermentations. However, a barrier to the heterologous
      production of more complex 'modular' polyketides in S. cerevisiae is the lack of
      required polyketide precursor pathways. In this work, we describe the
      introduction into S. cerevisiae of pathways for the production of methylmalonyl
      coenzyme A (CoA), a precursor for complex polyketides, by both propionyl-CoA
      dependent and propionyl-CoA-independent routes. Furthermore, we demonstrate that
      the methylmalonyl-CoA produced in the engineered yeast strains is used in vivo
      for the production of a polyketide product, a triketide lactone.

PMID- 16423070
TI  - Methionine catabolism in Saccharomyces cerevisiae.
AB  - The catabolism of methionine to methionol and methanethiol in Saccharomyces
      cerevisiae was studied using (13)C NMR spectroscopy, GC-MS, enzyme assays and a
      number of mutants. Methionine is first transaminated to alpha-keto-gamma
      (methylthio)butyrate. Methionol is formed by a decarboxylation reaction, which
      yields methional, followed by reduction. The decarboxylation is effected
      specifically by Ydr380wp. Methanethiol is formed from both methionine and alpha
      keto-gamma-(methylthio)butyrate by a demethiolase activity. In all except one
      strain examined, demethiolase was induced by the presence of methionine in the
      growth medium. This pathway results in the production of alpha-ketobutyrate, a
      carbon skeleton, which can be re-utilized. Hence, methionine catabolism is more
      complex and economical than the other amino acid catabolic pathways in yeast,
      which use the Ehrlich pathway and result solely in the formation of a fusel
      alcohol.

PMID- 16423071
TI  - The cellular resistance against oxidative stress (H2O2) is independent of neutral
      trehalase (Ntc1p) activity in Candida albicans.
AB  - The protective role of trehalose against oxidative stress caused by hydrogen
      peroxide in Candida albicans has been investigated in the homozygous mutant
      ntc1Delta/ntc1Delta, disrupted in the NTC1 gene, which encodes the neutral
      (cytosolic) trehalase (Ntc1p). After a severe oxidative exposure (50 mM
      H(2)O(2)), both parental (CAI-4) and ntc1Delta/ntc1Delta exponential-phase cells
      stored large amounts of intracellular trehalose. In turn, the degree of cell
      survival was roughly equivalent in both strains, although slightly higher in
      ntc1Delta/ntc1Delta cultures. The mechanism of 'adaptive tolerance' was
      functional in the two strains. Thus, a gently oxidative pretreatment (5 mM
      H(2)O(2)) increased the recovery of cellular viability when it was followed by a
      severe challenge (50 mM H(2)O(2)); this phenomenon was accompanied by a
      significant elevation of the endogenous trehalose content. Oxidative stress also
      induced specific activation of the antioxidant enzymes catalase and glutathione
      reductase upon gentle oxidative treatment (5 mM H(2)O(2)), whereas superoxide
      dismutase activity was only activated upon prolonged exposure. Taken together,
      these results strongly suggest that in C. albicans neutral trehalase activity
      does not play an essential role in the protective response against oxidative
      stress. They also suggest that a diminished Ntc1p activity might favour the
      growth of C. albicans cells subjected to a strong oxidative exposure.

PMID- 16423072
TI  - Extensive colonization of apples by smut anamorphs causes a new postharvest
      disorder.
AB  - Colonization of apples by ballistoconidium-forming fungi causes a new disorder,
      here named 'white haze'. White haze may occur in mild form in the field, but only
      becomes problematic after Ultra-Low Oxygen storage, and, therefore, may be
      considered as a postharvest disorder. All isolates, obtained using the spore-fall
      method, were morphologically identified as anamorphs of smut fungi belonging to
      the genus Tilletiopsis. Sequence analysis of the D1/D2 and the ITS domains of the
      rDNA revealed nine novel taxa scattered among the Exobasidiomycetidae
      (Ustilaginomycetes). Field experiments confirmed the erratic incidence of white
      haze over the years, and the development of the disorder seems to be enhanced at
      lower temperatures and a high relative humidity. Several scab fungicide
      treatments showed diminishing effects on the incidence of white haze.

PMID- 16423073
TI  - The mitochondrial genome of the wine yeast Hanseniaspora uvarum: a unique genome
      organization among yeast/fungal counterparts.
AB  - The complete sequence of the apiculate wine yeast Hanseniaspora uvarum mtDNA has
      been determined and analysed. It is an extremely compact linear molecule
      containing the shortest functional region ever found in fungi (11 094 bp long),
      flanked by Type 2 telomeric inverted repeats. The latter contained a 2704-bp-long
      subterminal region and tandem repeats of 839-bp units. In consequence, a
      population of mtDNA molecules that differed at the number of their telomeric
      reiterations was detected. The functional region of the mitochondrial genome
      coded for 32 genes, which included seven subunits of respiratory complexes and
      ATP synthase (the genes encoding for NADH oxidoreductase subunits were absent),
      two rRNAs and 23 tRNA genes which recognized codons for all amino acids. A single
      intron interrupted the cytochrome oxidase subunit 1 gene. A number of reasons
      contributed towards its strikingly small size, namely: (1) the remarkable size
      reduction (by >40%) of the rns and rnl genes; (2) that most tRNA genes and five
      of the seven protein-coding genes were the shortest among known yeast homologs;
      and (3) that the noncoding regions were restricted to 5.1% of the genome. In
      addition, the genome showed multiple changes in the orientation of transcription
      and the gene order differed drastically from other yeasts. When all protein
      coding gene sequences were considered as one unit and were compared with the
      corresponding molecules from all other complete mtDNAs of yeasts, the
      phylogenetic trees constructed robustly supported its placement basal to the
      yeast species of the 'Saccharomyces complex', demonstrating the advantage of this
      approach over single-gene or multigene approaches of unlinked genes.

PMID- 16423074
TI  - Metabolic profiling as a tool for revealing Saccharomyces interactions during
      wine fermentation.
AB  - The multi-yeast strain composition of wine fermentations has been well
      established. However, the effect of multiple strains of Saccharomyces spp. on
      wine flavour is unknown. Here, we demonstrate that multiple strains of
      Saccharomyces grown together in grape juice can affect the profile of aroma
      compounds that accumulate during fermentation. A metabolic footprint of each
      yeast in monoculture, mixed cultures or blended wines was derived by gas
      chromatography - mass spectrometry measurement of volatiles accumulated during
      fermentation. The resultant ion spectrograms were transformed and compared by
      principal-component analysis. The principal-component analysis showed that the
      profiles of compounds present in wines made by mixed-culture fermentation were
      different from those where yeasts were grown in monoculture fermentation, and
      these differences could not be produced by blending wines. Blending of
      monoculture wines to mimic the population composition of mixed-culture wines
      showed that yeast metabolic interactions could account for these differences.
      Additionally, the yeast strain contribution of volatiles to a mixed fermentation
      cannot be predicted by the population of that yeast. This study provides a novel
      way to measure the population status of wine fermentations by metabolic
      footprinting.

PMID- 16423075
TI  - Diversity and evolution of non-Saccharomyces yeast populations during wine
      fermentation: effect of grape ripeness and cold maceration.
AB  - We have evaluated the effect of grape maturity and cold maceration prior to
      fermentation on the yeast ecology during wine fermentation. Non-Saccharomyces
      strains were selectively isolated and identified using two rapid PCR techniques,
      namely enterobacterial repetitve intergenic consensus-PCR and PCR-intron splice
      sites, in various wine fermentation conditions. These identifications were
      further complemented and confirmed by restriction fragment length poymorphism and
      sequencing analysis of the 5.8S-ITS and D1/D2 ribosomal regions, respectively.
      Eleven species belonging to five genera were identified. Candida stellata,
      Hanseniaspora uvarum and Hanseniaspora osmophila were the dominant species,
      representing almost 90% of the isolates. Minor strains presented different
      species of the genera Candida, Issatchenkia, Zygoascus and Zygosaccharomyces.
      Selective isolation made it possible to isolate some species that were hardly
      related to the wine-making process, such as Issatchenkia hanoiensis, a new
      species that has only been described recently.

PMID- 16423076
TI  - Accounting for strain-specific differences during RTG target gene regulation in
      Saccharomyces cerevisiae.
AB  - Mitochondrial dysfunction results in the expression, via the retrograde response
      pathway, of a concise set of genes (RTG target genes) that encode enzymes
      involved in the anapleurotic production of alpha-ketoglutarate. Inhibiting the
      rapamycin-sensitive TOR kinases, important regulators of cell growth, similarly
      results in RTG target gene expression under rich nutrient conditions. Retrograde
      and TOR-dependent regulation of RTG target genes requires a number of shared
      components, including the heterodimeric bZip/HLH transcription factors Rtg1p and
      Rtg3p, as well as their upstream regulator Mks1p. Two unresolved discrepancies
      exist with regard to the mechanism of RTG target gene control: (1) deletion of
      MKS1 results in constitutive expression of RTG target genes in most but not all
      strain backgrounds; and (2) RTG target gene expression has been correlated with
      both decreased as well as increased Rtg3p phosphorylation. Here we have addressed
      both of these issues. First, we demonstrate that the mks1 deletion strain used in
      a previous study by Shamji and coworkers contains a nonsense mutation within
      codon Ser 231 in RTG3 that likely accounts for the inactivity of the RTG system
      in this strain. Second, we confirm results by Butow and coworkers that Rtg3p is
      dephosphorylated as a primary response to induction of the pathway. Hyper
      phosphorylation of this protein appears to be a secondary consequence of
      rapamycin treatment and is influenced both by strain background as well as by
      specific supplied nutrients. That hyper-phosphorylation of Rtg3p is also caused
      by heat shock suggests that it may reflect a more generalized response to cell
      stress. Together these results contribute toward a uniform view of RTG target
      gene regulation.

PMID- 16423077
TI  - Atomic force microscopic study of the influence of physical stresses on
      Saccharomyces cerevisiae and Schizosaccharomyces pombe.
AB  - Morphological changes in the cell surfaces of the budding yeast Saccharomyces
      cerevisiae (strain NCYC 1681), and the fission yeast Schizosaccharomyces pombe
      (strain DVPB 1354), in response to thermal and osmotic stresses, were
      investigated using an atomic force microscope. With this microscope imaging,
      together with measurements of culture viability and cell size, it was possible to
      relate topological changes of the cell surface at nanoscale with cellular stress
      physiology. As expected, when the yeasts were exposed to thermostress or
      osmostress, their viability together with the mean cell volume decreased in
      conjunction with the increase in thermal or osmotic shock. Nevertheless, the
      viability of cells stressed for up to 1 h remained relatively high. For example,
      viabilities were >50% and >90% for the thermostressed, and >60% and >70% for the
      osmostressed S. cerevisiae and Schiz. pombe, respectively. Mean cell volume
      measurements, and bearing and roughness analyses of atomic force microscope
      images of stressed yeasts indicate that Schiz. pombe may be more resistant to
      physical stresses than S. cerevisiae. Overall, this study has highlighted the
      usefulness of atomic force microscope in studies of yeast stress physiology.

PMID- 16423078
TI  - Hybrid filtering to rescue stable oscillations from noise-induced chaos in
      continuous cultures of budding yeast.
AB  - In large-scale fermentations with oscillating microbial cultures, noise is
      commonly present in the feed stream(s). As this can destabilize the oscillations
      and even generate chaotic behavior, noise filters are employed. Here three types
      of filters were compared by applying them to a noise-affected continuous culture
      of Saccharomyces cerevisiae with chaotic oscillations. The aim was to restore the
      original noise-free stable oscillations. An extended Kalman filter was found to
      be the least efficient, a neural filter was better and a combined hybrid filter
      was the best. In addition, better filtering of noise was achieved in the dilution
      rate than in the oxygen mass transfer coefficient. These results suggest the use
      of hybrid filters with the dilution rate as the manipulated variable for
      bioreactor control.

PMID- 16423079
TI  - The Eleventh International Congress of Mycology of the International Union of
      Microbiological Societies, San Francisco, California, 23-28 July 2005.

PMID- 16423080
TI  - Eighteenth 'Biology of Kluyveromyces' meeting, Bratislava, Slovakia, 6 August
      2005.

PMID- 16423081
TI  - The 23rd small meeting on Yeast Transport and Energetics (SMYTE), New Delhi
      (India), 23-26 September 2005.

PMID- 16423082
TI  - The 24th International Specialized Symposium on Yeasts (ISSY 24) "Cell surface: a
      genomic and proteomic approach" Oropesa del Mar (Castellon, Spain), 28 September
      2 October 2005.

PMID- 16423084
TI  - Isolation of Helicobacter pylori from the intestinal mucosa of patients with
      Crohn's disease.
AB  - BACKGROUND: Helicobacter species are associated with inflammatory bowel disease
      in rodents and in nonhuman primates. Therefore, we prospectively investigated the
      presence of Helicobacter species in the intestinal mucosa of patients with and
      without Crohn's disease by culture and polymerase chain reaction (PCR) assays.
      MATERIALS AND METHODS: Mucosal fragments were obtained from the ileum, different
      colon regions, and rectum of 43 patients with Crohn's disease and of 74 patients
      without inflammatory bowel disease. RESULTS: Helicobacter pylori strains,
      identified by 16S rRNA gene sequencing, were more frequently isolated and PCR
      detected in the intestinal mucosa of patients with ulcerative colitis-like
      Crohn's disease than in intestinal mucosa of the control group. Otherwise, anti
      H. pylori immunoglobulin G levels were significantly lower in fibrostenosing and
      fistulating Crohn's disease subgroups. No other Helicobacter species were found
      in the intestinal mucosa of the patients. CONCLUSIONS: Although our results
      suggest an association between the presence of H. pylori in the intestine and
      ulcerative colitis-like phenotype of Crohn's disease, H. pylori infection in the
      actual causality of Crohn's disease is still to be determined.

PMID- 16423086
TI  - Helicobacter pylori has stimulatory effects on naive T cells.
AB  - BACKGROUND: Despite an apparently active host response, Helicobacter pylori
      infection can persist for life. Unexpectedly, T cells from apparently uninfected
      individuals respond to H. pylori antigen by proliferating. Also, the T-cell
      proliferative response appears to be less in infected compared with uninfected
      individuals. MATERIALS AND METHODS: We have investigated the T-cell response of
      isolated human peripheral blood, naive, and memory CD4+ T cells to H. pylori
      antigen in infected and uninfected subjects. RESULTS: In agreement with previous
      findings, the peripheral blood proliferative response was higher in uninfected
      compared with infected subjects. Interestingly, there was a response in CD4+
      CD45RO+ (memory) and CD4+CD45RA+ (naive) subsets. The RO/RA ratio of the response
      to H. pylori antigen was 0.8-2.1 in both H. pylori-positive and H. pylori
      negative subjects, which was similar to that of a known superantigen (2.5 and 2.2
      in Helicobacter-positive and -negative subjects, respectively) whereas the RO/RA
      response ratio to a recall antigen (tetanus toxoid) was 9.8 and 18.7 in
      Helicobacter-positive and -negative subjects, respectively. Mononuclear cells
      isolated from cord blood also responded to H. pylori antigen, whereas there was
      no response to tetanus toxoid. The cord blood response and CD4+ CD45RA+ cell
      response to H. pylori antigen were inhibited predominantly by anti-HLA-DR and to
      some extent by anti-HLA-DQ antibodies. Investigation of the response to five
      different recombinant H. pylori antigens identified two that produced a response
      in naive T cells. CONCLUSIONS: These data suggest that H. pylori possesses
      molecules that cause higher than expected proliferation of naive T cells.

PMID- 16423085
TI  - Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2
      expression, apoptosis, and functional gastric mucosal impairment in Helicobacter
      pylori-infected Mongolian gerbils.
AB  - BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established
      experimental model of gastric carcinogenesis that mimics H. pylori-positive
      patients developing gastric ulcer and gastric cancer, but the effect of probiotic
      therapy on functional aspects of this infection remains unknown. METHODS: We
      compared the effects of intragastric inoculation of gerbils with H. pylori strain
      (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy
      including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil.
      Histology of glandular mucosa, the viable H. pylori, and density of H. pylori
      colonization were evaluated. The gastric blood flow was measured by H2-gas
      clearance method; the plasma gastrin and gastric luminal somatostatin were
      determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and
      Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori
      infection was detected in all animals by histology and H. pylori culture. Basal
      gastric acid was significantly reduced in H. pylori-infected animals but not in
      those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks
      upon H. pylori inoculation and consisted of chronic gastritis and glandular
      atypia associated with typical regenerative hyperplasia and increased mitotic
      activity and formation of apoptotic bodies. The H. pylori infection was
      accompanied by the fall in gastric blood flow, the marked increase in plasma
      gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein
      expression, and the rise in expression of COX-2 and Bax proteins. These mucosal
      changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H.
      pylori infection in gerbils, associated with regenerative hyperplasia of
      glandular structure, results in the suppression of gastric secretion,
      overexpression of COX-2, and enhancement in apoptosis and impairment of both,
      gastric blood flow and gastrin-somatostatin link that were reversed by anti-H.
      pylori triple therapy and attenuated by probiotics.

PMID- 16423087
TI  - Helicobacter pylori infection, but not low-dose aspirin, results in a local
      reduction of the secretory leukocyte protease inhibitor in gastroduodenal mucosa.
AB  - BACKGROUND: The secretory leukocyte protease inhibitor (SLPI) represents a
      multifunctional protein with mucosa-protective features. Helicobacter pylori and
      the usage of low-dose aspirin are two independent risk factors for the
      development of gastrointestinal diseases. Therefore, the effect of low-dose
      aspirin on gastrointestinal SLPI expression was analyzed in the context of H.
      pylori infection. MATERIAL AND METHODS: The study included 20 volunteers (H.
      pylori positive and negative: n = 10) who received 2 x 50 mg aspirin/day for 7
      days. H. pylori-positive subjects underwent eradication therapy and repeated the
      protocol. Gastroduodenoscopy was performed at day 0, 1, 3, and 7, and biopsies
      were obtained each from antrum, corpus, and duodenal bulb. SLPI expression was
      determined by quantitative reverse transcription-polymerase chain reaction (RT
      PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: A reduction of
      antral SLPI levels, ranging between 582 (day 0) and 941 pg/10 microg protein (day
      7), was determined in H. pylori-positive compared to H. pylori-negative and 
      eradicated subjects (1600-2050 pg/10 microg protein, ANOVA: p = .001-.045). No
      differences concerning aspirin were observed within the groups. SLPI levels in
      corpus and duodenal mucosa were neither affected by H. pylori nor low-dose
      aspirin. There was an inverse correlation between SLPI and H. pylori-induced
      inflammation (activity: r = -0.575, -0.69 to -0.43, p < .0001; chronicity: r = 
      0.54, -0.66 to -0.39, p < .0001) in antral mucosa only, whereas other locations
      as well as the usage of low-dose aspirin did not show an association between SLPI
      and inflammation. CONCLUSIONS: H. pylori infection, but not the usage of low-dose
      aspirin, has a role in the down-regulation of antral SLPI levels.

PMID- 16423088
TI  - 7-day triple therapy of Helicobacter pylori infection with levofloxacin,
      amoxicillin, and high-dose esomeprazole in patients with known antimicrobial
      sensitivity.
AB  - BACKGROUND AND AIMS: Failed primary anti-Helicobacter pylori therapy results in a
      high rate of antimicrobial resistance. This necessitates a search for new
      regimens to cure H. pylori infection. The aim of this study was to evaluate the
      efficacy and tolerability of a new levofloxacin-containing 7-day triple therapy
      and to compare it with that of standard French triple therapy in patients with
      known H. pylori susceptibility to MET (metronidazole) and CLA (clarithromycin).
      PATIENTS AND METHODS: Sixty-one patients with documented antibiotic sensitivity
      (E-test) and an indication for anti-H. pylori treatment based on the Maastricht
      Consensus 2/2000 guidelines were randomized to receive either esomeprazole 2 x 40
      mg, levofloxacin 2 x 500 mg, and amoxicillin 2 x 1 g for 7 days (ELA, n = 30), or
      esomeprazole 2 x 20 mg, clarithromycin 2 x 500 mg, and amoxicillin 2 x 1 g for 7
      days (ECA, n = 31). A cure check was performed 4-6 weeks after conclusion of
      therapy. RESULTS: Sixty-one patients were randomized to the two treatment groups.
      Twenty-eight of 30 patients of the ELA group were available for per-protocol (PP)
      analysis, of whom 26 (92.9% CI: 76-99%; intention-to-treat [ITT] analysis 86.7%
      CI: 68-96%) became H. pylori negative compared with 26 of the 31 patients of the
      ECA group (83.9%, CI: 66-93% both PP and ITT analyses). Five patients of the ELA
      group showed CLA resistance, three of whom also showed MET resistance, and all
      five were treated successfully. Two patients with levofloxacin-resistant strains,
      one in each group, were cured. Both regimens were generally well tolerated with
      minor adverse events being seen in 15 patients (51.7%) of the ELA group and in 13
      (40.6%) of the ECA group. None of the patients discontinued treatment prematurely
      due to adverse events. CONCLUSION: The data of this pilot study suggest a better
      than 80% efficacy of the new 7-day levofloxacin triple therapy, which is within
      the range of the French triple therapy in patients with MET- and CLA-susceptible
      strains. The data suggest that the new levofloxacin triple therapy may also be an
      option in patients with MET- and CLA-resistant H. pylori strains.

PMID- 16423089
TI  - Efficacy of moxifloxacin-based triple therapy as second-line treatment for
      Helicobacter pylori infection.
AB  - BACKGROUND AND AIM: Metronidazole and tetracycline-based second-line quadruple
      therapy, widely used for Helicobacter pylori infection, often ends up in failure
      due to antibiotic resistance and poor compliance in Korea. Our aim is to evaluate
      the efficacy and tolerability of moxifloxacin-based triple therapy as an
      alternative second-line treatment for H. pylori infection. METHODS: The subjects
      consisted of 85 patients infected with H. pylori, in whom initial proton pump
      inhibitor triple therapy had failed. They were randomized to receive the
      following 7-day therapy: 1, moxifloxacin 400 mg q.d., esomeprazole 20 mg b.i.d.,
      and amoxicillin 1 g b.i.d.; and 2, esomeprazole 40 mg b.i.d., tripotassium
      dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline
      500 mg q.i.d. Eradication rates, drug compliance, and side-effect rates of each
      group were evaluated. RESULTS: The eradication rates were 75.6 and 83.8% with
      moxifloxacin triple therapy, and 54.5 and 72.7% with quadruple therapy by
      intention-to-treat (p = .042) and per-protocol analyses (p = .260), respectively.
      Moxifloxacin triple therapy was significantly superior to quadruple therapy in
      terms of side-effect rates (p = .039). Compliance for therapy, i.e., the
      percentage of tablets taken (> 85%), was 90.2 and 75.0%, numerically higher in
      moxifloxacin triple therapy group than in quadruple therapy group, but without
      statistical difference (p = .065). CONCLUSIONS: Moxifloxacin-based triple therapy
      showed high eradication rates with few side effects and good drug compliance,
      suggesting this regimen could be a safe and effective option as second-line
      therapy for H. pylori infection in Korea.

PMID- 16423090
TI  - Twice-a-day quadruple therapy for eradication of Helicobacter pylori in the
      elderly.
AB  - BACKGROUND: Midday and evening twice-a-day quadruple therapy appears to be the
      most effective therapy for Helicobacter pylori infection in Northern Sardinia, a
      site where antibiotics resistance is common. AIM: The objective of our study was
      to estimate the efficacy, side-effects, and compliance of a quadruple therapy
      containing esomeprazole in a group of dyspeptic elderly patients. PATIENTS AND
      METHODS: Consecutive elderly patients positive for H. pylori infection and not
      previously treated for eradication were enrolled. Therapy consisted of
      esomeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth
      subcitrate tablets 240 mg, all twice-a-day with the midday and evening meals, for
      10 days. Efficacy was evaluated using 13C-urea breath testing. Compliance was
      assessed after completing treatment and at follow up. Side effects were graded
      based on daily activities. RESULTS: Ninety-five dyspeptic patients (range 65-81
      years), 52 men and 43 women, were enrolled. The intention-to-treat cure rate was
      91% (81 of 89; 95% CI = 88-99%) and, 95% (81 of 85; 95% CI = 83-96%) per-protocol
      analysis. Compliance was excellent. Mild-moderate side effects occurred in 27
      patients. CONCLUSIONS: Esomeprazole containing quadruple therapy was highly
      successful for initial eradication of H. pylori in elderly patients.

PMID- 16423092
TI  - Analysis of volatile compounds emitted by the Helicobacter pylori reference
      strain NCTC 11637 in vitro.

PMID- 16423091
TI  - Epidemiology of Helicobacter pylori infection in the Czech Republic.
AB  - BACKGROUND: Prevalence of Helicobacter pylori infection has been estimated to
      range from 60 to 95% in the former communist countries of Central and Eastern
      Europe. The aim of this study was to evaluate H. pylori infection prevalence in a
      representative sample of the Czech population. The second objective was to
      describe difference of H. pylori prevalence between different social groups of
      children and adults. MATERIALS AND METHODS: A total of 2509 persons aged 5-100
      years, randomly selected out of 30,012 persons of the general population, took
      part in the study. H. pylori infection was investigated by means of 13C-urea
      breath test. Breath samples were analyzed by isotope ratio mass spectrometry.
      Social and demographic characteristics were based on data from self-completed
      questionnaires. RESULTS: Using the total Czech population as a standard, we
      estimated the age-standardized prevalence of H. pylori in males aged 5+ years at
      41.9% (95% CI 39.0%, 44.8%) and in females aged 5+ years at 41.4% (95% CI 38.6%,
      44.3%) in 2001. Prevalence of H. pylori increased with age but was not related to
      gender. Children of mothers with basic or lower education, living in crowded
      accommodations, without access to running warm water, and residing in smaller
      towns appear to be at the highest risk. Low education and heavy smoking are most
      strongly associated with prevalence of H. pylori positivity in adults and
      adolescents. CONCLUSIONS: This is a unique study based on a representative sample
      of the general population in a Central European country. The overall prevalence
      of H. pylori is lower than previously assumed and could partly reflect a
      substantial recent decrease in H. pylori prevalence in the Czech Republic.
      Consistent with earlier studies, H. pylori infection is strongly influenced by
      socioeconomic conditions and childhood poverty.

PMID- 16423094
TI  - Physicians in retainer ("concierge") practice. A national survey of physician,
      patient, and practice characteristics.
AB  - BACKGROUND: Retainer practices represent a new model of care whereby physicians
      charge an up-front fee for services that may not be covered by health insurance.
      The characteristics of these practices are largely unknown. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted a cross-sectional mail survey of 144 retainer
      physicians (58% response rate) and a national random sample of 463 nonretainer
      physicians (50% response rate) to compare retainer and nonretainer practices.
      Outcomes of interest included physician demographics, size and case-mix of
      patient panel, services offered and, for retainer practices, characteristics of
      practice development. RESULTS: Retainer physicians have much smaller patient
      panels (mean 898 vs 2303 patients, P<.0001) than their nonretainer counterparts,
      and care for fewer African-American (mean 7% vs 16%, P<.002), Hispanic (4% vs
      14%, P<.001), or Medicaid (5% vs 15%, P<.001) patients. Physicians in retainer
      practices are more likely to offer accompanied specialist visits (30% vs 1%),
      house calls (63% vs 26%), 24-hour direct physician access (91% vs 40%), and
      several other services (all P values <.05). Most retainer physicians (85%)
      converted from nonretainer practices but kept few of their former patients (mean
      12%). Most retainer physicians (84%) provide charity care and many continue to
      see some patients (mean 17%) who do not pay retainer fees. CONCLUSIONS: Despite
      differences between retainer and nonretainer practices, there is also substantial
      overlap in services provided. These findings, in conjunction with the scope of
      patient discontinuity when physicians transition to retainer practice, suggest
      that ethical and legal debates about the standing of these practices will endure.

PMID- 16423095
TI  - Improving psychologic adjustment to chronic illness in cardiac patients. The role
      of depression and anxiety.
AB  - BACKGROUND: Poor mood adjustment to chronic medical illness is often accompanied
      by decrements in function. OBJECTIVE: To evaluate the effectiveness of a
      telephone-based intervention for psychologic distress and functional impairment
      in cardiac illness. DESIGN: Randomized, controlled trial. METHODS: We recruited
      survivors of acute coronary syndromes using the Hospital and Anxiety Depression
      Scale (HADS) with scores indicative of mood disturbances at 1-month
      postdischarge. Recruited patients were randomized to experimental or control
      status. Intervention patients received 6 30-minute telephone counseling sessions
      to identify and address illness-related fears and concerns. Control patients
      received usual care. Patients' responses to the HADS and the Workplace Social
      Adjustment Scale (WSAS) were collected at baseline, 2, 3, and 6 months using
      interactive voice recognition technology. At baseline, the PRIME-MD was used to
      establish diagnosis of depression. We used mixed effects regression to study
      changes in outcomes. RESULTS: We enrolled 100 patients. Mean age was 60; 67% of
      the patients were male. Findings confirmed that the intervention group had a 27%
      improvement in depression symptoms (P=.05), 27% in anxiety (P=.02), and a 38%
      improvement in home limitations (P=.04) compared with controls. Symptom
      improvement tracked those for WSAS measures of home function (P=.04) but not
      workplace function. CONCLUSIONS: The intervention had a moderate effect on
      patient's emotional and functional outcomes that were observed during a critical
      period in patients' lives. Patient convenience, ease of delivery, and the
      effectiveness of the intervention suggest that the counseling can help patients
      adjust to chronic illness.

PMID- 16423096
TI  - Hypertension outcomes through blood pressure monitoring and evaluation by
      pharmacists (HOME study).
AB  - OBJECTIVE: To evaluate the effectiveness of a community pharmacist-based home
      blood pressure (BP) monitoring program. DESIGN: Trial of a high-intensity (HI)
      versus low-intensity (LI) intervention randomized in 12 community pharmacies. The
      HI intervention comprised 4 face-to-face visits with a trained pharmacist.
      Pharmacists provided patient-specific education about hypertension. Following the
      first and third visits, patients were provided with a home BP monitoring device
      and instructed to measure their BP at least once daily for the next month. Home
      BP readings were used by the pharmacists to develop treatment recommendations for
      the patient's physician. Recommendations were discussed with the physician and,
      if approved, implemented by the pharmacist. In the LI intervention, pharmacists
      measured patients BP in the pharmacy and referred them to their physician for
      evaluation. PARTICIPANTS: Patients with uncontrolled BP at baseline.
      MEASUREMENTS: The main outcomes were the differences in systolic and diastolic BP
      (SBP and DBP) from baseline to follow-up between the HI and LI patients. RESULTS:
      The study enrolled 125 patients, 64 in the HI and 61 in the LI group. From
      baseline, SBP declined 13.4 mmHg in the HI group and 9.0 mmHg in the LI group. At
      the final visit, the difference in SBP/DBP change between the HI and LI group was
      -4.5/-3.2 mmHg (P=.12 for SBP and P=.03 for DBP). CONCLUSIONS: The HI
      intervention achieved a lower DBP and this model could be a strategy for patients
      with hypertension.

PMID- 16423097
TI  - Promoting use of colorectal cancer screening tests. Can we change physician
      behavior?
AB  - BACKGROUND: Colorectal cancer (CRC) screening is underutilized despite evidence
      that screening reduces mortality. OBJECTIVE: To assess the effect of an
      intervention targeting physicians and their patients on rates of CRC screening.
      DESIGN: A randomized clinical trial of community physicians and their patients.
      PARTICIPANTS: Ninety-four community primary care physicians randomly assigned to
      an intervention consisting of academic detailing and direct mailings to patients
      or a control group. Patients aged 50 to 79 years in the intervention group
      physicians received a letter from their physician, a brochure on CRC screening,
      and a packet of fecal occult blood test (FOBT) cards. MEASUREMENTS: After 1 year
      we measured receipt of the following: (1) FOBT in the past 2 years, (2) flexible
      sigmoidoscopy (SIG) or colonoscopy (COL) in the previous 5 years, and (3) any CRC
      screening. We report the percent change from baseline in both groups. RESULTS:
      9,652 patients were enrolled for 2 years, and 3,732 patients were enrolled for 5
      years. There was no increase in any CRC screening that occurred in the
      intervention group for patients enrolled for 2 years (12.7 increase vs 12.5%,
      P=.51). Similar results were seen for any CRC screening among patients enrolled
      for 5 years (9.7% increase vs 8.6%, P=.45). The only outcome on which the
      intervention had an effect was on patient rates of screening SIG (7.4% increase
      vs 4.4%, P<.01). CONCLUSION: With the exception of an increase in rates of SIG in
      the intervention group, the intervention had no effect on rates of CRC screening.
      Future interventions should assess innovative approaches to increase rates of CRC
      screening.

PMID- 16423098
TI  - Chlamydia screening and management practices of primary care physicians and nurse
      practitioners in California.
AB  - BACKGROUND: Because sexually transmitted chlamydial infections are common among
      young women, it is critical that providers screen and manage these infections
      appropriately. OBJECTIVE: To assess the Chlamydia care practices of California
      primary care physicians and nurse practitioners. DESIGN: Cross-sectional, self
      report mail survey. PARTICIPANTS: A stratified random sample of primary care
      physicians and a convenience sample of primary care nurse practitioners in
      California. MEASUREMENTS AND MAIN RESULTS: Survey content included 5 topic areas:
      sexual history taking, management of cervicitis, management of a nonpregnant
      Chlamydia-infected patient, availability of onsite STD services, and Chlamydia
      screening practices and attitudes. Main outcome measure was the reported
      frequency of Chlamydia screening of sexually active women age 25 and younger.
      Respondents included 708 physicians (49% response rate) and 895 nurse
      practitioners (63% response rate). Nearly half of physicians (47%, 95% confidence
      interval [CI], 42% to 51%) and a majority of nurse practitioners (79%, 95% CI,
      77% to 82%) reported routine Chlamydia screening of women under age 20; similar
      proportions reported routinely screening women aged 20 to 25 years. Independent
      predictors of screening among physicians were adolescent medicine specialty,
      female gender, practicing in a nonprivate setting, and having a higher volume of
      female patients. Additional findings included the overscreening of women over age
      25 by nurse practitioners and the shared concern among providers that Chlamydia
      screening may not be reimbursed. CONCLUSIONS: The Chlamydia care practices of
      many California primary care providers are inconsistent with current guidelines.
      Targeted provider education and improved reimbursements are potential strategies
      for improvement.

PMID- 16423099
TI  - Teaching medical students the important connection between communication and
      clinical reasoning.
AB  - BACKGROUND: Medical students are rarely taught how to integrate communication and
      clinical reasoning. Not understanding the relation between these skills may lead
      students to undervalue the connection between psychosocial and biomedical aspects
      of patient care. OBJECTIVE: To improve medical students' communication and
      clinical reasoning and their appreciation of how these skills interrelate in
      medical practice. DESIGN: In 2003, we conducted a randomized trial of a
      curricular intervention at Johns Hopkins University School of Medicine. In a 6
      week course, participants learned communication and clinical reasoning skills in
      an integrative fashion using small group exercises with role-play, reflection and
      feedback through a structured iterative reflective process. PARTICIPANTS: Second
      year medical students. MEASUREMENTS: All students interviewed standardized
      patients who evaluated their communication skills in establishing rapport, data
      gathering and patient education/counseling on a 5-point scale (1=poor;
      5=excellent). We assessed clinical reasoning through the number of correct
      problems listed and differential diagnoses generated and the Diagnostic Thinking
      Inventory. Students rated the importance of learning these skills in an
      integrated fashion. RESULTS: Standardized patients rated curricular students more
      favorably in establishing rapport (4.1 vs 3.9; P=.05). Curricular participants
      listed more psychosocial history items on their problem lists (65% of curricular
      students listing > or =1 item vs 44% of controls; P=.008). Groups did not differ
      significantly in other communication or clinical reasoning measures. Ninety-five
      percent of participants rated the integration of these skills as important.
      CONCLUSIONS: Intervention students performed better in certain communication and
      clinical reasoning skills. These students recognized the importance of biomedical
      and psychosocial issues in patient care. Educators may wish to teach the
      integration of these skills early in medical training.

PMID- 16423100
TI  - Psychosocial risk factors for adverse outcomes in patients with nonvalvular
      atrial fibrillation receiving warfarin.
AB  - OBJECTIVE: Our goal was to establish whether psychosocial risk factors for
      nonadherence, previously identified as negative predictors of warfarin
      prescribing, are predictors of adverse events for patients with nonvalvular
      atrial fibrillation receiving warfarin. DESIGN: Retrospective cohort analysis.
      SETTING: Ohio Medicaid administrative database. PATIENTS: We studied Ohio
      Medicaid recipients with nonvalvular atrial fibrillation receiving warfarin to
      determine whether a history of substance abuse, psychiatric illness, or social
      factors (identified as conditions perceived to be barriers to adherence) are
      predictors of adverse events, including stroke, intracranial hemorrhage, and
      gastrointestinal bleeding. Multivariable risk ratios were calculated for each
      risk factor using Cox proportional hazards models. RESULTS: 9,345 patients were
      identified as having nonvalvular atrial fibrillation and receiving 2 or more
      warfarin prescriptions between 1997 and 2002. The event rates for the sample as a
      whole were 1.5 strokes, 0.7 intracranial hemorrhages, and 4.3 gastrointestinal
      bleeds per 100 person-years of follow-up. Subjects with substance abuse had the
      highest adjusted risk ratio, 2.4 (95% confidence interval [CI]: 1.4, 4.0) for an
      intracranial hemorrhage while receiving warfarin, followed by subjects with
      psychiatric illness, adjusted risk ratio of 1.5 (95% CI: 1.04, 2.1). Subjects
      with psychiatric illness also had an adjusted risk ratio of 1.4 (95% CI: 1.1,
      1.7) for stroke. Patients in all 3 identified risk groups were at a significantly
      increased risk of gastrointestinal bleeding. CONCLUSION: Patients with
      nonvalvular atrial fibrillation treated with warfarin who have psychosocial risk
      factors for nonadherence have an increased risk of adverse events.

PMID- 16423101
TI  - Laboratory monitoring of drugs at initiation of therapy in ambulatory care.
AB  - BACKGROUND AND OBJECTIVES: Product labeling and published guidelines reflect the
      importance of monitoring laboratory parameters for drugs with a risk of organ
      system toxicity or electrolyte imbalance. Limited information exists about
      adherence to laboratory monitoring recommendations. The objective of this study
      was to describe laboratory monitoring among ambulatory patients dispensed
      medications for which laboratory testing is recommended at therapy initiation.
      DESIGN AND SUBJECTS: We conducted a retrospective cross-sectional analysis of
      patients in 10 geographically distributed health maintenance organizations who
      were newly prescribed medications with recommended laboratory test monitoring.
      The main outcome measure was the proportion of initial drug dispensing without
      recommended baseline laboratory monitoring for 35 newly initiated drugs or drug
      classes. RESULTS: One hundred seven thousand, seven hundred sixty-three of
      279,354 (39%) initial drug dispensings occurred without recommended laboratory
      monitoring. Patients without monitoring were younger than patients who had
      monitoring (median 57 vs 61 years, P<.001). Thirty-two percent of dispensings
      where a serum creatinine was indicated did not have it evaluated (range across
      drugs, 12% to 61%); 39% did not have liver function testing (range 10% to 75%);
      32% did not have hematologic monitoring (range 9% to 51%); and 34% did not have
      electrolyte monitoring (range 20% to 62%) (P<.001). CONCLUSIONS: Substantial
      opportunity exists to improve laboratory monitoring of drugs for which such
      monitoring is recommended. This study emphasizes the need for research to
      identify the clinical implications of not conducting recommended laboratory
      monitoring, existing barriers to monitoring, and methods to improve practice.

PMID- 16423102
TI  - Cardiac risk underestimation in urban, black women.
AB  - BACKGROUND: Black women have a disproportionately higher incidence of
      cardiovascular disease mortality than other groups and the reason for this health
      disparity is incompletely understood. Underestimation of personal cardiac risk
      may play a role. OBJECTIVE: We investigated the personal characteristics
      associated with underestimating cardiovascular disease in black women. DESIGN,
      SETTING, PARTICIPANTS: Trained surveyors interviewed 128 black women during the
      baseline evaluation for a randomized controlled trial in an urban, academic
      continuity clinic affiliated with a public hospital system. They provided
      information on the presence of cardiac risk factors and demographic and
      psychosocial characteristics. These self-report data were supplemented with
      medical record abstraction for weight. MEASUREMENTS AND MAIN RESULTS: The main
      outcome measure was the accurate perception of cardiac risk. Objective risk was
      determined by a simple count of major cardiac risk factors and perceived risk by
      respondent's answer to a survey question about personal cardiac risk. The burden
      of cardiac risk factors was high in this population: 77% were obese; 72% had
      hypertension; 48% had high cholesterol; 49% had a family history of heart
      disease; 31% had diabetes, and 22% currently used tobacco. Seventy-nine percent
      had 3 or more cardiac risk factors. Among those with 3 or more risk factors
      ("high risk"), 63% did not perceive themselves to be at risk for heart disease.
      Among all patients, objective and perceived cardiac risk was poorly correlated
      (kappa=0.026). In a multivariable model, increased perceived personal stress and
      lower income were significant correlates of underestimating cardiac risk.
      CONCLUSIONS: Urban, disadvantaged black women in this study had many cardiac risk
      factors, yet routinely underestimated their risk of heart disease. We found that
      the strongest correlates of underestimation were perceived stress and lower
      personal income.

PMID- 16423103
TI  - Physicians' initial management of acute low back pain versus evidence-based
      guidelines. Influence of sciatica.
AB  - BACKGROUND: Little information is available on physician characteristics and
      patient presentations that may influence compliance with evidence-based
      guidelines for acute low back pain. OBJECTIVE: To assess whether physicians'
      management decisions are consistent with the Agency for Health Research Quality's
      guideline and whether responses varied with the presentation of sciatica or by
      physician characteristics. DESIGN: Cross-sectional study using a mailed survey.
      PARTICIPANTS: Participants were randomly selected from internal medicine, family
      practice, general practice, emergency medicine, and occupational medicine
      specialties. MEASUREMENTS: A questionnaire asked for recommendations for 2 case
      scenarios, representing patients without and with sciatica, respectively.
      RESULTS: Seven hundred and twenty surveys were completed (response rate=25%). In
      cases 1 (without sciatica) and 2 (with sciatica), 26.9% and 4.3% of physicians
      fully complied with the guideline, respectively. For each year in practice, the
      odds of guideline noncompliance increased 1.03 times (95% confidence interval
      [CI]=1.01 to 1.05) for case 1. With occupational medicine as the referent
      specialty, general practice had the greatest odds of noncompliance (3.60, 95%
      CI=1.75 to 7.40) in case 1, followed by internal medicine and emergency medicine.
      Results for case 2 reflected the influence of sciatica with internal medicine
      having substantially higher odds (vs case 1) and the greatest odds of
      noncompliance of any specialty (6.93, 95% CI=1.47 to 32.78), followed by family
      practice and emergency medicine. CONCLUSIONS: A majority of primary care
      physicians continue to be noncompliant with evidence-based back pain guidelines.
      Sciatica dramatically influenced clinical decision-making, increasing the extent
      of noncompliance, particularly for internal medicine and family practice.
      Physicians' misunderstanding of sciatica's natural history and belief that more
      intensive initial management is indicated may be factors underlying the observed
      influence of sciatica.

PMID- 16423104
TI  - A pilot study evaluating mindfulness-based stress reduction and massage for the
      management of chronic pain.
AB  - BACKGROUND: Mindfulness-based stress reduction (MBSR) and massage may be useful
      adjunctive therapies for chronic musculoskeletal pain. OBJECTIVE: To evaluate the
      feasibility of studying MBSR and massage for the management of chronic pain and
      estimate their effects on pain and mood. DESIGN: Randomized trial comparing MBSR
      or massage with standard care. PARTICIPANTS: Thirty patients with chronic
      musculoskeletal pain. MEASUREMENTS: Pain was assessed with 0 to 10 numeric rating
      scales. Physical and mental health status was measured with the SF-12. RESULTS:
      The study completion rate was 76.7%. At week 8, the massage group had average
      difference scores for pain unpleasantness of 2.9 and mental health status of 13.6
      compared with 0.13 (P<.05) and 3.9 (P<.04), respectively, for the standard care
      group. These differences were no longer significant at week 12. There were no
      significant differences in the pain outcomes for the MBSR group. At week 12, the
      mean change in mental health status for the MBSR group was 10.2 compared with 
      1.7 in the standard care group (P<.04). CONCLUSIONS: It is feasible to study MBSR
      and massage in patients with chronic musculoskeletal pain. Mindfulness-based
      stress reduction may be more effective and longer-lasting for mood improvement
      while massage may be more effective for reducing pain.

PMID- 16423105
TI  - Identification and management of overweight and obesity by internal medicine
      residents.
AB  - BACKGROUND: Obesity is a major cause of morbidity and mortality in the United
      States. OBJECTIVE: To assess how frequently Internal Medicine residents identify
      and manage overweight and obese patients and to determine patient characteristics
      associated with identification and management of overweight compared with
      obesity. DESIGN: A cross-sectional medical record review. PATIENTS: Four hundred
      and twenty-four overweight or obese primary care patients from 2 Internal
      Medicine resident clinics in Connecticut. MEASUREMENTS: Measurements included the
      frequency with which obese and overweight patients were identified as such by
      their resident physicians, patient demographics, and co-morbid illnesses, as well
      as use of management strategies for excess weight. RESULTS: In this population of
      obese and overweight patients, obese patients were identified and treated more
      often compared with overweight patients (76/246%, 30.9% vs 12/178%, 7.3% for
      identification, P=.001, and 59/246%, 24.0% vs 11/178%, 6.2% for treatment,
      P=.001). Overall, only 70/424 (17%) of patients received any form of management.
      Only higher body mass index (BMI) (BMI> or =30 kg/m2 compared with BMI 25-29.9
      kg/m2) was independently associated with identification of overweight or obesity
      (odds ratio 7.51%, 95% confidence interval [CI] 3.76 to 15.02) or with any
      management for excess weight (odds ratio 4.79%, 95% CI 2.44 to 9.42).
      CONCLUSIONS: Our results suggest that Internal Medicine residents markedly
      underrecognize and undertreat overweight and obesity.

PMID- 16423106
TI  - The impact of cigarette smoking on mortality, quality of life, and comorbid
      illness among HIV-positive veterans.
AB  - BACKGROUND: The impact of smoking on outcomes among those with HIV infection has
      not been determined in the era of highly active antiretroviral therapy (HAART).
      STUDY OBJECTIVE: Determine the impact of smoking on morbidity and mortality in
      HIV-positive patients post-HAART. DESIGN: Prospective observational study.
      PARTICIPANTS: Eight hundred and sixty-seven HIV-positive veterans enrolled in the
      Veterans Aging Cohort 3 Site Study. MEASUREMENTS: Clinical data were collected
      through patient questionnaire, International Classification of Diseases--9th
      edition codes, and standardized chart extraction, and laboratory and mortality
      data through the national VA database. Quality of life was assessed with the
      physical component summary (PCS) of the Short-Form 12. RESULTS: Current smokers
      had increased respiratory symptoms, chronic obstructive pulmonary disease (COPD),
      and bacterial pneumonia. In analyses adjusted for age, race/ethnicity, CD4 cell
      count, HIV RNA level, hemoglobin, illegal drug and alcohol use, quality of life
      was substantially decreased (beta=-3.3, 95% confidence interval [CI] -5.3 to 
      1.4) and mortality was significantly increased (hazard ratio 1.99, 95% CI 1.03 to
      3.86) in current smokers compared with never smokers. CONCLUSIONS: HIV-positive
      patients who currently smoke have increased mortality and decreased quality of
      life, as well as increased respiratory symptoms, COPD, and bacterial pneumonia.
      These findings suggest that smoking cessation should be emphasized for HIV
      infected patients.

PMID- 16423107
TI  - Ineffective communication of mental status information during care transfer of
      older adults.
AB  - BACKGROUND: Monitoring and documenting the mental status of older patients
      transferred between providers or facilities is important because mental status
      change can be a sign of acute disease and mental status abnormalities necessitate
      specific approaches to care. OBJECTIVES: To identify patient and illness factors
      associated with presence of a mental status description in inter-facility
      transfer documents and to describe the content and concurrent validity of
      transfer mental status descriptions when they occur. DESIGN: Retrospective study.
      PARTICIPANTS: Individuals transferred between 5 long-term and 2 acute care
      facilities in an urban setting. MEASUREMENTS: Trained research personnel reviewed
      hospital and nursing home medical records and inter-facility transfer documents.
      Mental status descriptions in transfer documents were coded as abnormal or normal
      within 5 domains: alertness, communication, orientation/memory, behavior, and
      mood. Descriptions were compared with mental status items in the nursing home
      Minimum Data Set and in a transfer communication checklist. RESULTS: In all, 123
      nursing home residents experienced 174 hospital admissions. Mental status
      descriptions were present in 69% of transfer documents. A total of 67% of
      patients missing a transfer mental status description upon nursing home-to
      hospital transfer had dementia. Factors associated with presence of a transfer
      mental status description were urgent transfer, nursing home of origin, and among
      patients without dementia, greater cognitive impairment. When present, a mean of
      1.47 (SD=0.81) cognitive domains were documented in transfer mental status
      descriptions. Agreement between transfer mental status descriptions and
      comparison sources was fair to good (kappa=.31 to .73). CONCLUSION: Mental status
      documentation during transfer of older adults between nursing home and hospital
      did not identify all patients with dementia and did not completely characterize
      patients' cognitive status.

PMID- 16423108
TI  - The efficacy and safety of exogenous melatonin for primary sleep disorders. A
      meta-analysis.
AB  - BACKGROUND: Exogenous melatonin has been increasingly used in the management of
      sleep disorders. PURPOSE: To conduct a systematic review of the efficacy and
      safety of exogenous melatonin in the management of primary sleep disorders. DATA
      SOURCES: A number of electronic databases were searched. We reviewed the
      bibliographies of included studies and relevant reviews and conducted hand
      searching. STUDY SELECTION: Randomized controlled trials (RCTs) were eligible for
      the efficacy review, and controlled trials were eligible for the safety review.
      DATA EXTRACTION: One reviewer extracted data, while the other verified data
      extracted. The Random Effects Model was used to analyze data. DATA SYNTHESIS:
      Melatonin decreased sleep onset latency (weighted mean difference [WMD]: -11.7
      minutes; 95% confidence interval [CI]: -18.2, -5.2)); it was decreased to a
      greater extent in people with delayed sleep phase syndrome (WMD: -38.8 minutes;
      95% CI: -50.3, -27.3; n=2) compared with people with insomnia (WMD: -7.2 minutes;
      95% CI: -12.0, -2.4; n=12). The former result appears to be clinically important.
      There was no evidence of adverse effects of melatonin. CONCLUSIONS: There is
      evidence to suggest that melatonin is not effective in treating most primary
      sleep disorders with short-term use (4 weeks or less); however, additional large
      scale RCTs are needed before firm conclusions can be drawn. There is some
      evidence to suggest that melatonin is effective in treating delayed sleep phase
      syndrome with short-term use. There is evidence to suggest that melatonin is safe
      with short-term use (3 months or less).

PMID- 16423109
TI  - What is the validity evidence for assessments of clinical teaching?
AB  - BACKGROUND: Although a variety of validity evidence should be utilized when
      evaluating assessment tools, a review of teaching assessments suggested that
      authors pursue a limited range of validity evidence. OBJECTIVES: To develop a
      method for rating validity evidence and to quantify the evidence supporting
      scores from existing clinical teaching assessment instruments. DESIGN: A
      comprehensive search yielded 22 articles on clinical teaching assessments. Using
      standards outlined by the American Psychological and Education Research
      Associations, we developed a method for rating the 5 categories of validity
      evidence reported in each article. We then quantified the validity evidence by
      summing the ratings for each category. We also calculated weighted kappa
      coefficients to determine interrater reliabilities for each category of validity
      evidence. MAIN RESULTS: Content and Internal Structure evidence received the
      highest ratings (27 and 32, respectively, of 44 possible). Relation to Other
      Variables, Consequences, and Response Process received the lowest ratings (9, 2,
      and 2, respectively). Interrater reliability was good for Content, Internal
      Structure, and Relation to Other Variables (kappa range 0.52 to 0.96, all P
      values < .01), but poor for Consequences and Response Process. CONCLUSIONS:
      Content and Internal Structure evidence is well represented among published
      assessments of clinical teaching. Evidence for Relation to Other Variables,
      Consequences, and Response Process receive little attention, and future research
      should emphasize these categories. The low interrater reliability for Response
      Process and Consequences likely reflects the scarcity of reported evidence. With
      further development, our method for rating the validity evidence should prove
      useful in various settings.

PMID- 16423111
TI  - Internal medicine training in the inpatient setting. A review of published
      educational interventions.
AB  - PURPOSE: Although the inpatient setting has served as the predominant educational
      site of internal medicine training programs, many changes and factors are
      currently affecting education in this setting. As a result, many educational
      organizations are calling for reforms in inpatient training. This report reviews
      the available literature on specific internal medicine inpatient educational
      interventions and proposes recommendations for improving internal medicine
      training in this setting. METHOD: We searched Medline for articles published
      between 1966 and August 2004 which focused on internal medicine training
      interventions in the inpatient setting; bibliographies of Medline-identified
      articles, as well as articles suggested by experts in the field provided
      additional citations. We then reviewed, classified, and abstracted only articles
      where an assessment of learner outcomes was included. RESULTS: Thirteen studies
      of inpatient internal medicine educational interventions were found that included
      an outcome assessment. All were single institution studies. The majority of these
      studies was of poor methodological quality and focused on specific content areas
      of internal medicine. None assessed the effectiveness or impact of internal
      medicine core inpatient experiences or curriculum. CONCLUSION: This review
      identifies significant gaps in our understanding of what constitutes effective
      inpatient education. The paucity of high quality research in the internal
      medicine inpatient setting highlights the urgent need to formally define and
      study what constitutes an effective "core" inpatient curriculum.

PMID- 16423110
TI  - Reforming internal medicine residency training. A report from the Society of
      General Internal Medicine's task force for residency reform.

PMID- 16423113
TI  - READY... SET... GO ... internal medicine residency reform for the 21st century.

PMID- 16423112
TI  - Changing habits of practice. Transforming internal medicine residency education
      in ambulatory settings.
AB  - PURPOSE: The majority of health care, both for acute and chronic conditions, is
      delivered in the ambulatory setting. Despite repeated proposals for change, the
      majority of internal medicine residency training still occurs in the inpatient
      setting. Substantial changes in ambulatory education are needed to correct the
      current imbalance. To assist educators and policy makers in this process, this
      paper reviews the literature on ambulatory education and makes recommendations
      for change. METHODS: The authors searched the Medline, Psychlit, and ERIC
      databases from 2000 to 2004 for studies that focused specifically on curriculum,
      teaching, and evaluation of internal medicine residents in the ambulatory setting
      to update previous reviews. Studies had to contain primary data and were reviewed
      for methodological rigor and relevance. RESULTS: Fifty-five studies met criteria
      for review. Thirty-five of the studies focused on specific curricular areas and
      11 on ambulatory teaching methods. Five involved evaluating performance and 4
      focused on structural issues. No study evaluated the overall effectiveness of
      ambulatory training or investigated the effects of current resident continuity
      clinic microsystems on education. CONCLUSION: This updated review continues to
      identify key deficiencies in ambulatory training curriculum and faculty skills.
      The authors make several recommendations: (1) Make training in the ambulatory
      setting a priority. (2) Address systems problems in practice environments. (3)
      Create learning experiences appropriate to the resident's level of development.
      (4) Teach and evaluate in the examination room. (5) Expand subspecialty-based
      training to the ambulatory setting. (6) Make faculty development a priority. (7)
      Create and fund multiinstitutional educational research consortia.

PMID- 16423114
TI  - Concierge care and the future of general internal medicine.

PMID- 16423116
TI  - Teaching cardiac examination skills. A controlled trial of two methods.
AB  - OBJECTIVE: To determine if structured teaching of bedside cardiac examination
      skills improves medical residents' examination technique and their identification
      of key clinical findings. DESIGN: Firm-based single-blinded controlled trial.
      SETTING: Inpatient service at a university-affiliated public teaching hospital.
      PARTICIPANTS: Eighty Internal Medicine residents. METHODS: The study assessed 2
      intervention groups that received 3-hour bedside teaching sessions during their 4
      week rotation using either: (1) a traditional teaching method, "demonstration and
      practice" (DP) (n=26) or (2) an innovative method, "collaborative discovery" (CD)
      (n=24). The control group received their usual ward teaching sessions (n=25). The
      main outcome measures were scores on examination technique and correct
      identification of key clinical findings on an objective structured clinical
      examination (OSCE). RESULTS: All 3 groups had similar scores for both their
      examination technique and identification of key findings in the preintervention
      OSCE. After teaching, both intervention groups significantly improved their
      technical examination skills compared with the control group. The increase was
      10% (95% confidence interval [CI] 4% to 17%) for CD versus control and 12% (95%
      CI 6% to 19%) for DP versus control (both P<.005) equivalent to an additional 3
      to 4 examination skills being correctly performed. Improvement in key findings
      was limited to a 5% (95% CI 2% to 9%) increase for the CD teaching method, CD
      versus control P=.046, equivalent to the identification of an additional 2 key
      clinical findings. CONCLUSIONS: Both programs of bedside teaching increase the
      technical examination skills of residents but improvements in the identification
      of key clinical findings were modest and only demonstrated with a new method of
      teaching.

PMID- 16423117
TI  - Impact of instructional practices on student satisfaction with attendings'
      teaching in the inpatient component of internal medicine clerkships.
AB  - OBJECTIVE: To determine the prevalence and influence of specific attending
      teaching practices on student evaluations of the quality of attendings' teaching
      in the inpatient component of Internal Medicine clerkships. DESIGN: Nationwide
      survey using a simple random sample. SETTING: One hundred and twenty-one
      allopathic 4-year medical schools in the United States. PARTICIPANTS: A total of
      2,250 fourth-year medical students. MEASUREMENTS AND MAIN RESULTS: In the spring
      of 2002, student satisfaction with the overall quality of teaching by attendings
      in the inpatient component of Internal Medicine clerkships was measured on a 5
      point scale from very satisfied to very dissatisfied (survey response rate,
      68.3%). Logistic regression was used to determine the association of specific
      teaching practices with student evaluations of the quality of their attendings'
      teaching. Attending physicians' teaching practices such as engaging students in
      substantive discussions (odds ratio (OR)=3.0), giving spontaneous talks and
      prepared presentations (OR=1.6 and 1.8), and seeing new patients with the team
      (OR=1.2) were strongly associated with higher student satisfaction, whereas
      seeming rushed and eager to finish rounds was associated with lower satisfaction
      (OR=0.6). CONCLUSION: Findings suggest that student satisfaction with attendings'
      teaching is high overall but there is room for improvement. Specific teaching
      behaviors used by attendings affect student satisfaction. These specific
      behaviors could be taught and modified for use by attendings and clerkship
      directors to enhance student experiences during clerkships.

PMID- 16423118
TI  - Measuring patients' experiences with individual primary care physicians. Results
      of a statewide demonstration project.
AB  - BACKGROUND: Measuring and reporting patients' experiences with health plans has
      been routine for several years. There is now substantial interest in measuring
      patients' experiences with individual physicians, but numerous concerns remain.
      OBJECTIVE: The Massachusetts Ambulatory Care Experiences Survey Project was a
      statewide demonstration project designed to test the feasibility and value of
      measuring patients' experiences with individual primary care physicians and their
      practices. DESIGN: Cross-sectional survey administered to a statewide sample by
      mail and telephone (May-August 2002). PATIENTS: Adult patients from 5 commerical
      health plans and Medicaid sampled from the panels of 215 generalist physicians at
      67 practice sites (n=9,625). MEASUREMENTS: Ambulatory Care Experiences Survey
      produces 11 summary measures of patients' experiences across 2 domains: quality
      of physician-patient interactions and organizational features of care. Physician
      level reliability was computed for all measures, and variance components analysis
      was used to determine the influence of each level of the system (physician, site,
      network organization, plan) on each measure. Risk of misclassifying individual
      physicians was evaluated under varying reporting frameworks. RESULTS: All
      measures except 2 achieved physician-level reliability of at least 0.70 with
      samples of 45 patients per physician, and several exceeded 0.80. Physicians and
      sites accounted for the majority of system-related variance on all measures, with
      physicians accounting for the majority on all "interaction quality" measures
      (range: 61.7% to 83.9%) and sites accounting for the largest share on
      "organizational" measures (range: 44.8% to 81.1%). Health plans accounted for
      neglible variance (<3%) on all measures. Reporting frameworks and principles for
      assuring misclassification risk < or =2.5% were identified. CONCLUSIONS: With
      considerable national attention on the importance of patient-centered care, this
      project demonstrates the feasibility of obtaining highly reliable measures of
      patients' experiences with individual physicians and practices. The analytic
      findings underscore the validity and importance of looking beyond health plans to
      individual physicians and sites as we seek to improve health care quality.

PMID- 16423119
TI  - Randomized controlled trial of an informatics-based intervention to increase
      statin prescription for secondary prevention of coronary disease.
AB  - OBJECTIVE: Suboptimal treatment of hyperlipidemia in patients with coronary
      artery disease (CAD) is well documented. We report the impact of a computer
      assisted physician-directed intervention to improve secondary prevention of
      hyperlipidemia. DESIGN AND SETTING: Two hundred thirty-five patients under the
      care of 14 primary care physicians in an academically affiliated practice with an
      electronic health record were enrolled in this proof-of-concept physician-blinded
      randomized, controlled trial. Each patient with CAD or risk equivalent above
      National Cholesterol Education Program-recommended low-density lipoprotein (LDL)
      treatment goal for greater than 6 months was randomized, stratified by physician
      and baseline LDL. Physicians received a single e-mail per intervention patient. E
      mails were visit independent, provided decision support, and facilitated "one
      click" order writing. MEASUREMENTS: The primary outcomes were changes in
      hyperlipidemia prescriptions, time to prescription change, and changes in LDL
      levels. The time spent using the system was assessed among intervention patients.
      RESULTS: A greater proportion of intervention patients had prescription changes
      at 1 month (15.3% vs 2%, P=.001) and 1 year (24.6% vs 17.1%, P=.14). The median
      interval to first medication adjustment occurred earlier among intervention
      patients (0 vs 7.1 months, P=.005). Among patients with baseline LDLs >130 mg/dL,
      the first postintervention LDLs were substantially lower in the intervention
      group (119.0 vs 138.0 mg/dL, P=.04). Physician processing time was under 60
      seconds per e-mail. CONCLUSION: A visit-independent disease management tool
      resulted in significant improvement in secondary prevention of hyperlipidemia at
      1-month postintervention and showed a trend toward improvement at 1 year.

PMID- 16423121
TI  - Medical patients' attitudes toward emotional problems and their treatment. What
      do they really want?
AB  - BACKGROUND: Understanding medical patients' attitudes toward emotional problems
      and their management is crucial to overcoming obstacles to efficient depression
      treatment. OBJECTIVE: To investigate attitudes toward emotional problems,
      psychotherapy, antidepressants, alternative treatment approaches, and self
      management techniques in depressed and nondepressed medical outpatients. DESIGN:
      Cross-sectional interview study, including quantitative and qualitative methods.
      PATIENTS: Eighty-seven depressed subjects (mean age, 41.0 years; 66% female) and
      91 nondepressed subjects (mean age, 41.4 years; 67% female) from 7 internal
      medicine outpatient clinics and 12 family practices (participation rate, 91%).
      MEASUREMENTS: Depression diagnoses were established using a structured diagnostic
      interview, and patient attitudes were investigated with open-ended interview
      questions regarding treatment preferences, factors improving and impairing
      emotional well-being, and patients' self-management to improve well-being.
      RESULTS: Among the depressed patients, psychotherapy was the most frequently
      preferred treatment (29%) and the most common factor reported to improve
      emotional well-being (36%). Twenty-two percent of the depressed patients desired
      depression treatment within their current medical system, but requested
      substantially more time to communicate with their physician. Antidepressants were
      rarely mentioned as a preferred treatment (6%) or factor improving well-being
      (11%). Thirty-eight percent of the depressed patients attributed their impaired
      mood to health problems. Compared with the depressed patients, the nondepressed
      controls preferred significantly less frequent depression-specific therapies.
      CONCLUSIONS: The vast majority of medical outpatients prefer treatment approaches
      for emotional problems that go beyond antidepressant medication therapy. Health
      care providers should consider providing sufficient time to communicate with
      their patients, the strong preference for psychotherapy, and an appropriate
      treatment of comorbid physical conditions.

PMID- 16423120
TI  - Prevalence of depression in survivors of acute myocardial infarction.
AB  - OBJECTIVES: To assess the prevalence and persistence of depression in patients
      with acute myocardial infarction (AMI) and the relationship between assessment
      modality and prevalence. DATA SOURCES: MEDLINE, Cochrane, CINAHL, PsycINFO, and
      EMBASE. REVIEW METHODS: A comprehensive search was conducted in March 2004 to
      identify original research studies published since 1980 that used a standardized
      interview or validated questionnaire to assess depression. The search was
      augmented by hand searching of selected journals from October 2003 through April
      2004 and references of identified articles and reviews. Studies were excluded if
      only an abstract was provided, if not in English, or if depression was not
      measured by a validated method. RESULTS: Major depression was identified in 19.8%
      (95% confidence interval [CI] 19.1% to 20.6%) of patients using structured
      interviews (N=10,785, 8 studies). The prevalence of significant depressive
      symptoms based on a Beck Depression Inventory score > or =10 was 31.1% (CI 29.2%
      to 33.0%; N=2,273, 6 studies), using a Hospital Anxiety and Depression Scale
      (HADS) score > or =8%, 15.5% (CI 13.2% to 18.0%; N=863, 4 studies), and with a
      HADS score > or =11%, 7.3% (CI 5.5% to 9.3%; N=830, 4 studies). Although a
      significant proportion of patients continued to be depressed in the year after
      discharge, the limited number of studies and variable follow-up times precluded
      specification of prevalence rates at given time points. CONCLUSIONS: Depression
      is common and persistent in AMI survivors. Prevalence varies depending on
      assessment method, likely reflecting treatment of somatic symptoms.

PMID- 16423123
TI  - Uncovering frustrations. A qualitative needs assessment of academic general
      internists as geriatric care providers and teachers.
AB  - BACKGROUND: General internists commonly provide medical care for older adults and
      geriatric education to trainees, but lack the necessary knowledge and skills to
      fulfill these tasks. OBJECTIVE: Assess the geriatric training needs of academic
      general internists in 3 hospital systems in Portland, OR. DESIGN: Ten focus
      groups and 1 semi-structured interview. Interview transcripts were analyzed using
      thematic analysis, a well-recognized qualitative technique. PARTICIPANTS: A
      convenience sample of 22 academic general internists and 8 geriatricians from 3
      different teaching hospitals. MEASUREMENTS: We elicited stories of frustration
      and success in caring for elderly patients and in teaching about their care. We
      asked geriatricians to recount their experiences as consultants to general
      internists and to comment on the training of Internists in geriatrics. RESULTS:
      In addition to deficits in their medical knowledge and skills, our Internists
      reported frustration with the process of delivering care to older adults. In
      particular, they felt ill prepared to guide care transitions for patients, use
      multidisciplinary teams effectively, and were frustrated with health care system
      issues. Additionally, general internists' approach to medical care, which largely
      relies on the medical model, is different from that of geriatricians, which
      focuses more on social and functional issues. CONCLUSIONS: Although our findings
      may not be broadly representative, improving our general internists' abilities to
      care for the elderly and to teach learners how to do the same should address
      deficits in medical knowledge and skills, barriers to the processes of delivering
      care, and philosophical approaches to care. Prioritizing and quantifying these
      needs and measuring the effectiveness of curricula to address them are areas for
      future research.

PMID- 16423122
TI  - Screening, assessment, and management of depression in VA primary care clinics.
      The Behavioral Health Laboratory.
AB  - OBJECTIVES: The purpose of this project was to assess the utility and feasibility
      of a telephone-based systematic clinical assessment service, the Behavioral
      Health Laboratory (BHL), in the context of primary care. The BHL is a clinical
      service that provides primary care providers with an assessment and a summary of
      mental health and substance abuse (MH/SA) symptoms and provides treatment
      decision support, including triage to specialty MH/SA services. The BHL was
      implemented to assist in the evaluation of patients who screened positively for
      depression at an annual clinical appointment or who were identified through
      routine care. METHODS: Results from systematic screening of primary care patients
      were extracted during a period of 6 months prior to implementation of the BHL and
      after implementation of the BHL. Descriptive results of the 580 evaluations
      conducted during this time were available. RESULTS: Results suggest an
      association between the implementation of the BHL and an increase in the
      proportion of patients screened for depression in primary care. In addition,
      there was an increase in the proportion of patients who screened positively (2.8%
      vs 7.0%). The BHL was successful in providing a comprehensive assessment for 78%
      of those referred. Significant co-occurring mental illness and substance misuse
      were found among those assessed. CONCLUSIONS: Introducing the BHL into primary
      care was associated with an apparent change in clinical practice in primary care
      at the Philadelphia VA Medical Center. Not only were more patients identified,
      the broad-based approach of the BHL identified significant comorbidity with
      alcohol misuse, illicit drugs, and suicidal ideation, symptoms likely to have
      been missed in routine clinical practice. The BHL offers a practical, low-cost
      method of assessment, monitoring, and treatment planning for patients identified
      in primary care with MH/SA needs.

PMID- 16423124
TI  - Men's theories about benign prostatic hyperplasia and prostate cancer following a
      benign prostatic hyperplasia decision aid.
AB  - OBJECTIVE: To use qualitative methods to explore audiotape evidence of
      unanticipated confusion between benign prostatic hyperplasia (BPH) and prostate
      cancer in using a videotape BPH treatment decision aid (DA). DESIGN: Qualitative
      analysis of semi-structured interviews and surveys originally collected to study
      men's interpretation of a DA. SETTING AND PARTICIPANTS: Community sample of
      college and noncollege educated African American and white men (age> or =50;
      n=188). MEASURES: Transcript analysis identified themes in men's comments about
      BPH and cancer. Surveys measured BPH general and prostate cancer-specific
      knowledge, literacy (Short Test of Functional Health Literacy in Adults), BPH
      symptoms, and demographics. RESULTS: In transcript analysis, 18/188 men
      spontaneously talked about BPH and cancer as being related to each other, despite
      explicit statements to the contrary in the video. Survey data suggest that up to
      126/188 men (67%) persisted in misconceptions even after viewing the DA video.
      Three themes were identified in the transcripts: (1) BPH and cancer are equated,
      (2) BPH surgery is for the purpose of removing cancer, and (3) BPH leads to
      cancer. CONCLUSIONS: Overall knowledge increases with DA use may mask incorrect
      theories of disease process. Further research should identify decision support
      designs and clinical counseling strategies to address persistence of beliefs
      contrary to new information presented in evidence-based DAs.

PMID- 16423125
TI  - Brief report: Factors associated with depression among homeless and marginally
      housed HIV-infected men in San Francisco.
AB  - OBJECTIVES: To evaluate the prevalence of and factors associated with depression
      among HIV-infected homeless and marginally housed men. DESIGN: Cross-sectional
      study. PARTICIPANTS AND SETTING: Homeless and marginally housed men living with
      HIV in San Francisco identified from the Research on Access to Care in the
      Homeless (REACH) Cohort. MEASUREMENTS: The primary outcome was symptoms of
      depression, as measured by the Beck Depression Inventory (BDI). Multivariate
      logistic regression was used to identify associations of sociodemographic
      characteristics, drug and alcohol use, housing status, jail status, having a
      representative payee, health care utilization, and CD4 T lymphocyte counts.
      RESULTS: Among 239 men, 134 (56%) respondents screened positive for depression.
      Variables associated with depression in multivariate analysis included white race
      (adjusted odds ratio [AOR]=2.2, confidence interval [CI]=1.3 to 3.9), having a
      representative payee (AOR=2.4, CI=1.3 to 4.2), heavy alcohol consumption
      (AOR=4.7, CI=1.3 to 17.1), and recently missed medical appointments (AOR=2.6,
      CI=1.4 to 4.8). CONCLUSIONS: Depression is a major comorbidity among the HIV
      infected urban poor. Given that missed medical appointments and alcohol use are
      likely indicators of depression and contributors to continued depression,
      alternate points of contact are necessary with many homeless individuals.
      Providers may consider partnering with payees to improve follow-up with
      individuals who are HIV-positive, homeless, and depressed.

PMID- 16423126
TI  - Brief report: Utility of a short screening scale for DSM-IV PTSD in primary care.
AB  - OBJECTIVE: To evaluate Breslau's 7-item screen for posttraumatic stress disorder
      (PTSD) for use in primary care. DESIGN: One hundred and thirty-four patients were
      recruited from primary care clinics at a large medical center. Participants
      completed the self-administered 7-item PTSD screen. Later, psychologists blinded
      to the results of the screen-interviewed patients using the Clinician
      Administered PTSD Scale (CAPS). Sensitivity, specificity, and likelihood ratios
      (LR) were calculated using the CAPS as the criterion for PTSD. RESULTS: The
      screen appears to have test-retest reliability (r=.84), and LRs range from 0.04
      to 13.4. CONCLUSIONS: Screening for PTSD in primary care is time efficient and
      has the potential to increase the detection of previously unrecognized PTSD.

PMID- 16423127
TI  - Brief report: Housestaff adherence to cervical cancer screening recommendations.
AB  - BACKGROUND: Postgraduate training involves intensive clinical education
      characterized by long work hours with minimal flexibility. Time demands may be a
      barrier to obtaining preventive care for housestaff during postgraduate training.
      OBJECTIVE: Assess adherence to United States Preventive Services Task Force
      (USPSTF) cervical cancer screening recommendations. DESIGN: Cross-sectional
      survey. PARTICIPANTS: Convenience sample of female housestaff at 1 university
      hospital. MEASUREMENTS: Primary outcomes included (1) adherence to USPSTF
      recommendations, (2) perception of adherence to recommendations, and (3) barriers
      to obtaining preventive care. RESULTS: Surveys were completed by 204 housestaff.
      Overall, 81% of housestaff were adherent to USPSTF screening recommendations.
      Housestaff requiring screening in the past year were less likely to be adherent
      when compared with housestaff requiring screening in the past 3 years. Overall,
      84% accurately perceived their screening behavior as adherent or nonadherent
      (kappa=0.58). Of the 43% who identified a barrier to obtaining preventive care,
      not having time to schedule or keep appointments was reported most frequently
      (n=72). CONCLUSIONS: Housestaff accurately perceived their need for cervical
      cancer screening and were generally adherent to USPSTF recommendations, even
      though lack of time during postgraduate training was frequently reported as a
      barrier to obtaining preventive care. However, we found lower adherence among a
      small subgroup of housestaff at a slightly greater risk for cervical disease and
      most likely to benefit from screening.

PMID- 16423128
TI  - Housing instability and food insecurity as barriers to health care among low
      income Americans.
AB  - BACKGROUND: Homelessness and hunger are associated with poor health outcomes.
      Housing instability and food insecurity describe less severe problems securing
      housing and food. OBJECTIVE: To determine the association between housing
      instability and food insecurity and access to ambulatory health care and rates of
      acute health care utilization. DESIGN: Secondary data analysis of the National
      Survey of American Families. PARTICIPANTS: 16,651 low-income adults. MEASUREMENT:
      Self-reported measures of past-year access: (1) not having a usual source of
      care, (2) postponing needed medical care, or (3) postponing medication; and past
      year utilization: (1) not having an ambulatory care visit, (2) having emergency
      department (ED) visits, or (3) inpatient hospitalization. RESULTS: 23.6% of
      subjects had housing instability and 42.7% had food insecurity. In multivariate
      logistic regression models, housing instability was independently associated with
      not having a usual source of care (adjusted odds ratio [AOR] 1.31, 95% confidence
      interval [CI] 1.08 to 1.59), postponing needed medical care (AOR 1.84, 95% CI
      1.46 to 2.31) and postponing medications (AOR 2.16, 95% CI 1.70 to 2.74),
      increased ED use (AOR: 1.43, 95% CI 1.20 to 1.70), and hospitalizations (AOR
      1.30, 95% CI 1.01 to 1.67). Food insecurity was independently associated with
      postponing needed medical care (AOR 1.74, 95% CI 1.38 to 2.21) and postponing
      medications (AOR 2.15, 95% CI 1.62 to 2.85), increased ED use (AOR 1.39, 95% CI
      1.17 to 1.66), and hospitalizations (AOR 1.42, 95% CI 1.09 to 1.85). CONCLUSIONS:
      Housing instability and food insecurity are associated with poor access to
      ambulatory care and high rates of acute care. These competing life demands may
      lead to delays in seeking care and predispose to acute care.

PMID- 16423129
TI  - Neuropsychological predictors of decision-making capacity over 9 months in mild
      to-moderate dementia.
AB  - BACKGROUND: Older adults with dementia may have diminished capacity to make
      medical treatment decisions. OBJECTIVE: To examine rates and neuropsychological
      predictors of treatment decision making, or consent capacity, among older adults
      with dementia over 9 months. DESIGN: Consent capacity was assessed initially and
      9 months later in subjects with and without dementia using a longitudinal
      repeated measures design. PARTICIPANTS: Fifty-three older adults with dementia
      and 53 similarly aged adults without dementia. MEASUREMENTS: A standardized
      measure MacArthur Competence Assessment Tool-Treatment of 4 legal standards for
      capacity (Understanding, Appreciation, Reasoning, and Expressing a Choice) and a
      neuropsychological battery. RESULTS: In the dementia group, 9.4% had impaired
      capacity initially, and 26.4% had impaired capacity at 9 months. Mean scores in
      the dementia group were impaired relative to controls initially and at 9 months
      for Understanding (initial t=2.49, P=.01; 9-month t=3.22, P<.01) and Reasoning
      (initial t=2.18, P=.03; 9-month t=4.77, P<.01). Declining capacity over 9 months
      was attributable to a further reduction in Reasoning (group x time F=9.44,
      P=.003). Discriminant function analysis revealed that initial scores on naming,
      delayed Logical Memory, and Trails B were associated with impaired capacity at 9
      months. CONCLUSIONS: Some patients with mild-to-moderate dementia develop a
      clinically relevant impairment of consent capacity within a year. Consent
      capacity in adults with mild-to-moderate dementia should be reassessed
      periodically to ensure that it is adequate for each specific informed consent
      situation. Interventions that maximize Understanding and Reasoning by supporting
      naming, memory, and flexibility may help to optimize capacity in this patient
      group.

PMID- 16423131
TI  - A language problem.

PMID- 16423130
TI  - Preventing diabetes in the clinical setting.
AB  - OBJECTIVE: Translating lessons from clinical trials on the prevention or delay of
      type 2 diabetes to populations in nonstudy settings remains a challenge. The
      purpose of this paper is to review, from the perspective of practicing
      clinicians, available evidence on lifestyle interventions or medication to
      prevent or delay the onset of type 2 diabetes. DESIGN: A MEDLINE search
      identified 4 major diabetes prevention trials using lifestyle changes and 3 using
      prophylactic medications. We reviewed the study design, key components, and
      outcomes for each study, focusing on aspects of the interventions potentially
      adaptable to clinical settings. RESULTS: The lifestyle intervention studies set
      modest goals for weight loss and physical activity. Individualized counseling
      helped participants work toward their own goals; behavioral contracting and self
      monitoring were key features, and family and social context were emphasized.
      Study staff made vigorous follow-up efforts for subjects having less success.
      Actual weight loss by participants was modest; yet, the reduction in diabetes
      incidence was quite significant. Prophylactic medication also reduced diabetes
      risk; however, lifestyle changes were more effective and are recommended as first
      line strategy. Cost-effectiveness analyses have shown both lifestyle and
      medication interventions to be beneficial, especially as they might be
      implemented in practice. CONCLUSION: Strong evidence exists for the prevention or
      delay of type 2 diabetes through lifestyle changes. Components of these programs
      may be adaptable for use in clinical settings. This evidence supports broader
      implementation and increased reimbursement for provider services related to
      nutrition and physical activity to forestall morbidity from type 2 diabetes.

PMID- 16423133
TI  - Swimming upstream. Access, health outcomes, and the social determinants of
      health.

PMID- 16423134
TI  - Using videotaped vignettes to teach medical students to perform the neurologic
      examination.

PMID- 16423135
TI  - Comments on Rangel et al., "Racial and ethnic disparities in influenza
      vaccination...".

PMID- 16423136
TI  - The corporate co-author, the ghostwriter, and the medical society: an object
      lesson (June, 2005 issue).

PMID- 16423138
TI  - Response to "Interactions between pharmaceutical representatives and doctors in
      training: a thematic review".

PMID- 16423140
TI  - Comments on Thavendiranathan et al. Do blood tests cause anemia in hospitalized
      patients?

PMID- 16423141
TI  - Understanding developmental psychopathology: two steps forward; one step back?

PMID- 16423142
TI  - Practitioner review: use of antiepileptic drugs in children.
AB  - BACKGROUND: The aim in treating epilepsy is to minimise or control seizures with
      full respect of quality-of-life issues, especially of cognitive functions.
      Optimal treatment first demands a correct recognition of the major type of
      seizures, followed by a correct diagnosis of the type of epilepsy or of the
      specific syndrome. METHODS: Review of data from literature and personal clinical
      experience in treating children with epilepsy. RESULTS: After summarising the
      general aspects on the diagnosis and treatment of the main forms of childhood
      epilepsy, we review key issues about management of seizure disorders, including
      when to start treatment, how to proceed when the first treatment fails, and how
      to set the targets of treatment. A special section is devoted to the new concept
      of epileptic encephalopathy and to the influence of "interictal" EEG
      abnormalities on cognition, behaviour, and motor abilities in children, providing
      some suggestions on why and how to treat these conditions. A second section
      approaches the choice of treatment according to the specific syndromes including
      infantile spasms, focal epilepsies, syndromes with typical absence seizures, the
      myoclonic epilepsies and the Lennox-Gastaut syndrome. CONCLUSIONS: Antiepileptic
      drugs (AEDs) can efficiently control seizures in most children. However, the
      specificity of AEDs is relatively limited, although continuing research is
      leading to a better understanding of the relationship between pathogenesis and
      the mechanism(s) and site(s) of drug action.

PMID- 16423143
TI  - A randomised controlled trial to determine the effectiveness of an early
      psychological intervention with children involved in road traffic accidents.
AB  - OBJECTIVE: To determine whether an early intervention using a psychological
      debriefing format is effective in preventing psychological distress in child road
      traffic accident survivors. DESIGN: Randomised controlled trial. SETTING:
      Accident and Emergency Department, Royal United Hospital, Bath. SUBJECTS: 158
      children aged 7-18. Follow-up assessment completed eight months post accident
      with 132 (70/82 of the experimental group and 62/76 in the control group). MAIN
      OUTCOME MEASURES: Self-completed measures of psychological distress; fulfilment
      of diagnostic criteria for post-traumatic stress disorder. RESULTS: Children in
      both groups demonstrated considerable improvements at follow-up. The early
      intervention did not result in any additional significant gains. CONCLUSIONS:
      Although children in this study made significant improvements it is unclear
      whether these are better or worse than natural recovery rates. The specific
      intervention did not result in additional gains although the structured
      assessment provided for both groups may have been helpful in reducing subsequent
      pathology.

PMID- 16423144
TI  - Psychostimulant and other effects of caffeine in 9- to 11-year-old children.
AB  - BACKGROUND: Recent research on adults suggests that "beneficial" psychostimulant
      effects of caffeine are found only in the context of caffeine deprivation; that
      is, caffeine improves psychomotor and cognitive performance in habitual caffeine
      consumers following caffeine withdrawal. Furthermore, no net benefit is gained
      because performance is merely restored to "baseline" levels. The effects of
      caffeine in children is an under-researched area, with only a handful of studies
      being carried out in the US where children's consumption of caffeine appears to
      be lower on average than in the UK. METHOD: Twenty-six children aged between 9
      and 11 years completed a double-blind, placebo-controlled study. Habitual
      caffeine consumers (mean daily caffeine intake = 109 mg) and non/low-consumers
      (12 mg) were tested on two separate days following overnight caffeine abstinence.
      On each day measures of cognitive performance (a number search task), and self
      rated mood and physical symptoms, including alertness and headache, were taken
      before and after administration of 50 mg of caffeine, or placebo. RESULTS: At
      baseline (before treatment), the habitual consumers showed poorer performance on
      the cognitive test than did the non/low-consumers, although no significant
      differences in mood or physical symptoms were found between the two groups. There
      were significant habit by treatment (caffeine vs. placebo) interactions for
      accuracy of performance and headache, and a significant main effect of treatment
      for alertness. Post hoc comparisons showed that caffeine administration improved
      the consumers' accuracy on the cognitive test (to near the level displayed by the
      non/low-consumers at baseline), but that it had no significant effect on the
      non/low-consumers' performance. In the consumers, caffeine prevented an increase
      in headache that occurred after placebo, and it increased alertness relative to
      placebo. Again, however, caffeine did not significantly affect levels of headache
      or alertness in the non/low-consumers. CONCLUSIONS: These results suggest that,
      like adults, children probably derive little or no benefit from habitual caffeine
      intake, although negative symptoms associated with overnight caffeine withdrawal
      are avoided or rapidly reversed by subsequent caffeine consumption.

PMID- 16423145
TI  - Children's subjective emotional reactivity to affective pictures: gender
      differences and their antisocial correlates in an unselected sample of 7-11-year
      olds.
AB  - BACKGROUND: Differential responses in terms of gender and antisocial behaviour in
      emotional reactivity to affective pictures using the International Affective
      Picture System (IAPS) have been demonstrated in adult and adolescent samples.
      Moreover, a quadratic relationship between the arousal (intensity) and valence
      (degree of unpleasantness) has been suggested. The picture perception methodology
      has rarely been applied to middle school-aged children. We examined the
      subjective ratings of emotional reactivity in children for: i) the relationship
      between arousal and valence, ii) gender differences, and iii) its association
      with measures of antisocial behaviour. METHOD: Twenty-seven IAPS pictures were
      selected to cover a wide range of affective content and were individually
      administered to a non-referred community sample of 659 7-11-year-old children
      using a paper-and-pencil version. Concurrent symptoms of conduct disorder,
      oppositional defiance and psychopathy were collected from multiple sources
      (teacher-, parent- and self-report). RESULTS: A quadratic relationship between
      arousal and valence, similar to that previously reported in adults, was
      demonstrated. A gender difference was found for valence ratings, with girls
      rating aversive pictures more unpleasant than boys. No gender differences for
      arousal ratings were found. A significant difference was found between groups
      scoring above and below cut-off scores on measures of antisocial behaviour.
      Children above cut-off reported lower arousal to unpleasant pictures, but higher
      arousal to pleasant pictures. CONCLUSIONS: We confirmed that a paper-and-pencil
      version of the IAPS for evaluating emotion response to affectively valent and
      arousing stimuli can be used in school settings and that comparable gender
      differences in emotional reactivity can be found in children. The differential
      emotional reactivity of children above cut-off on measures of antisocial
      behaviour suggested these symptoms to be associated with a combination of
      increased reward and decreased punishment sensitivity.

PMID- 16423146
TI  - Personality differences in children and adolescents with attention
      deficit/hyperactivity disorder, conduct disorder, and controls.
AB  - BACKGROUND: Differences in personality profiles were examined between children
      who differed in their co-morbidity of externalizing disorders: attention
      deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). METHODS: 11- and
      17-year-old male and female twins from a community sample were categorized as
      ADHD only, CD only, co-morbid CD-ADHD, and controls (no ADHD or CD) based on
      threshold and subthreshold CD and ADHD diagnoses assessed with structured
      interviews. Multivariate analyses were used to identify patterns of personality
      that differentiate these four diagnostic groups. It was hypothesized that
      significant differences would be found in the pattern of personality variables
      between participants in the co-morbid group, compared to the other three groups,
      and that these differences would hold across developmental periods. RESULTS: As
      expected, the co-morbid group had a pattern of personality marked by higher
      Negative Emotionality and lower Constraint than the other diagnostic groups. This
      pattern was evidenced across gender and age cohort. CONCLUSIONS: An extreme
      personality profile may represent a liability toward the occurrence of ADHD and
      CD with more extreme profiles contributing to the occurrence of both disorders
      among boys and girls. Implications for treatment planning and theoretical
      development are discussed.

PMID- 16423147
TI  - The Obsessive Compulsive Scale of the Child Behavior Checklist predicts obsessive
      compulsive disorder: a receiver operating characteristic curve analysis.
AB  - BACKGROUND: The purpose of this study was to determine a score on the Obsessive
      Compulsive Scale (OCS) from the Child Behavior Checklist (CBCL) to screen for
      obsessive compulsive disorder (OCD) in children and to rigorously test the
      specificity and sensitivity of a single cutpoint. METHODS: A receiver operating
      characteristic (ROC) curve analysis was applied to data from 61 patients with
      clinically determined OCD, 64 clinical controls and 73 general population
      controls to determine the best sum score on the CBCL-OCS to predict confirmed OCD
      in children. Using the ROC-determined cutoff, this score was applied to a
      national sample of CBCL data from 2460 singleton children ages 4-18 and to 20,016
      children ages 7-18 from three large general population twin samples to determine
      the estimated prevalence in the general population. RESULTS: Using a CBCL-OCS
      score of 5 demonstrated an area under the curve (AUC) of .88 with high
      sensitivity (92%) and moderate specificity (67%) compared to clinical controls.
      Compared to the general population controls, the AUC was .96 with high
      sensitivity (92%) and specificity (89%). In the twin samples, the number of
      participants with CBCL-OCS scores above this cutpoint was 2.3-7.1%. CONCLUSIONS:
      These findings suggest that the OCS of the CBCL may provide a highly effective
      way to screen for childhood OCD, and that the prevalence of childhood OCD may
      have been underestimated, thus prompting the need for further research into
      screening children for this condition.

PMID- 16423148
TI  - Autistic features in a total population of 7-9-year-old children assessed by the
      ASSQ (Autism Spectrum Screening Questionnaire).
AB  - BACKGROUND: The prevalence of autism is reported to be on the rise worldwide.
      Change of diagnostic criteria and a broadening of the concept of autism have been
      mentioned as contributing factors. Further studies of general populations are
      needed. The present study assessed the distribution of autistic features in a
      total population of children 7-9 years of age, and explored the impact of age,
      gender, informant, and participation bias on symptom report. METHODS: Teacher and
      parent forms of the Autism Spectrum Screening Questionnaire (ASSQ) were used in
      the "Bergen Child Study", a total population study of 9430 children aged 7-9
      years. Completed teacher forms were returned for 97% and parent forms for 71% of
      the children. High-scorers were defined according to the ASSQ validation study by
      Ehlers, Gillberg, and Wing (1999). RESULTS: The distribution of ASSQ scores was
      found to be almost continuous. Of the children with both a teacher and a parent
      form, 2.1% were defined as high-scorers. Children without parent informed consent
      (i.e., anonymous children) obtained significantly higher teacher scores than
      those who had questionnaires completed by both parent and teacher. Adjusting
      prevalence for the anonymous children, the prevalence of high-scorers was 2.7% of
      the total population. Age did not affect symptom scores. Boys scored higher and
      parents reported more symptoms, particularly in girls. Agreement between
      informants was low to moderate. CONCLUSIONS: Autism symptoms are not uncommon in
      the general population of children. Our findings are consistent with the concept
      of autism as a spectrum. Non-responders had a higher load of autism symptoms than
      identified children, indicating that reports on the prevalence of autism in a
      responder group underestimate true prevalence. Large differences across
      informants suggested the need to gather information both from families and from
      schools when screening for autism spectrum disorders.

PMID- 16423149
TI  - Towards a typology of specific language impairment.
AB  - BACKGROUND: The population of children with specific language impairments (SLI)
      is heterogeneous. The present study was conducted to examine this heterogeneity
      more closely, by identifying and describing subgroups within the population of
      children with SLI in the Netherlands. METHOD: A broad battery of language tests
      and language-related cognitive tests were administered to 147 six-year-old and
      136 eight-year-old children with SLI. RESULTS: Factor analyses revealed 4 factors
      indicating 4 distinctive linguistic domains for both age samples: 1) lexical
      semantic abilities, 2) auditory conceptualization, 3) verbal sequential memory
      and 4) speech production. These empirical findings were further validated by the
      positive correlations found between the language factors and the judgments of
      teachers and speech therapists. Finally, a cluster analysis revealed 4 distinct
      clusters of SLI children for each sample with specific language profiles based on
      the 4 factors. Results were nearly the same for both age samples. CONCLUSIONS:
      The language problems that emerged from the two samples of children with SLI
      could be described as falling into four types. Based on these language types,
      four subgroups of children with SLI could be distinguished, each with a specific
      profile. Some subgroups had severe problems on one specific type of language
      problem; others had severe problems in more than one type of language problem
      when compared to the other subgroups of the same age sample. The different
      profiles may indicate that a more dynamic approach is needed in intervention,
      considering the presence of both compensating and restricting factors within each
      child with SLI.

PMID- 16423151
TI  - Phonology and handedness in primary school: predictions of the right shift
      theory.
AB  - BACKGROUND: The right shift (RS) theory of handedness suggests that poor
      phonology may occur in the general population as a risk associated with absence
      of an agent of left cerebral speech, the hypothesised RS + gene. The theory
      predicts that poor phonology is associated with reduced bias to right-handedness.
      METHODS: A representative cohort of primary school children was assessed on tests
      of phonology, nonverbal ability, literacy, and handedness. There were three types
      of analysis; for discrete variables, poor phonology and left hand preference; for
      continuous variables, phonology factor scores and hand skill; for "cases" of
      specifically poor phonology. RESULTS: Reduced bias to dextrality was found in
      those with poor phonology for all types of analysis. Trends were similar for both
      sexes but stronger in males than females. Poor phonology was associated with a
      raised proportion of left-handed brothers. There was a strong association between
      poor phonology and poor literacy, but not all those with specifically poor
      phonology were poor readers or spellers. Among children with poor phonology but
      not poor for other variables, some 23-31% were left-handed writers. CONCLUSIONS:
      Poor phonological processing is associated with reduced bias to the right hand,
      consistent with absence of an agent of left hemisphere advantage.

PMID- 16423150
TI  - Are numerical impairments syndrome specific? Evidence from Williams syndrome and
      Down's syndrome.
AB  - BACKGROUND: Several theorists maintain that exact number abilities rely on
      language-relevant processes whereas approximate number calls on visuo-spatial
      skills. We chose two genetic disorders, Williams syndrome and Down's syndrome,
      which differ in their relative abilities in verbal versus spatial skills, to
      examine this hypothesis. Five experiments assessed number skills in these two
      genetic syndromes and in their mental age (MA) and chronological age (CA) matched
      controls. METHODS: Experiment 1 used a preferential looking paradigm with infants
      and toddlers to measure sensitivity to changes in numerosity. Experiment 2
      measured reaction times in older children and adults in a numerosity comparison
      task with dots in a random pattern. Experiment 3 comprised a number battery that
      measured various forms of counting and simple arithmetic. RESULTS: The WS infants
      displayed a level of performance equal to that of their CA-controls, whereas the
      DS infants failed to reach even the level of their MA-controls. By contrast, the
      older DS children and adults outstripped the older WS group in their numerosity
      abilities, with different patterns of errors in the two clinical groups.
      CONCLUSIONS: Differences in the infant and adult number phenotypes between these
      two genetic disorders are discussed with reference to the processing styles used
      by each group and how these might impact on their developmental trajectories.
      Theoretically, we highlight our contention that one cannot infer the infant
      starting state from the adult end state. Rather, the development process itself
      must be taken into account.

PMID- 16423152
TI  - Surrogacy families: parental functioning, parent-child relationships and
      children's psychological development at age 2.
AB  - BACKGROUND: Findings are presented of the second phase of a longitudinal study of
      families created through surrogacy. METHODS: At the time of the child's 2nd
      birthday, 37 surrogacy families were compared with 48 egg donation families and
      68 natural conception families on standardised interview and questionnaire
      measures of the psychological well-being of the parents, parent-child
      relationships and the psychological functioning of the child. RESULTS: The
      surrogacy mothers showed more positive parent-child relationships, and the
      surrogacy fathers reported lower levels of parenting stress, than their natural
      conception counterparts. The surrogacy children did not differ from the natural
      conception children with respect to socio-emotional or cognitive development.
      CONCLUSIONS: Surrogacy does not appear to impact negatively on parenting or child
      development in families with 2-year-old children.

PMID- 16423157
TI  - Standardized remission criteria in schizophrenia.

PMID- 16423158
TI  - The gluten connection: the association between schizophrenia and celiac disease.
AB  - OBJECTIVE: Schizophrenia affects roughly 1% of the population and is considered
      one of the top 10 causes of disability worldwide. Given the immense cost to
      society, successful treatment options are imperative. Based on initial findings,
      gluten withdrawal may serve as a safe and economical alternative for the
      reduction of symptoms in a subset of patients. METHOD: A review of the literature
      relevant to the association between schizophrenia and celiac disease (gluten
      intolerance) was conducted. RESULTS: A drastic reduction, if not full remission,
      of schizophrenic symptoms after initiation of gluten withdrawal has been noted in
      a variety of studies. However, this occurs only in a subset of schizophrenic
      patients. CONCLUSION: Large-scale epidemiological studies and clinical trials are
      needed to confirm the association between gluten and schizophrenia, and address
      the underlying mechanisms by which this association occurs.

PMID- 16423159
TI  - Standardized remission criteria in schizophrenia.
AB  - OBJECTIVE: Recent work has focussed on schizophrenia as a 'deficit' state but
      little attention has been paid to defining illness plasticity in terms of
      symptomatic remission. METHOD: A qualitative review of a recently proposed
      concept of remission [N.C. Andreasen, W.T. Carpenter Jr, J.M. Kane, R.A. Lasser,
      S.R. Marder, D.R. Weinberger (2005) Am J Psychiatry 162: 441] is presented.
      RESULTS: The proposed definition of remission is conceptually viable, and can be
      easily implemented in clinical trials and clinical practice. Its increasing
      acceptance may reset expectations of treatment to a higher level, improve
      documentation of clinical status and facilitate dialogue on treatment
      expectations. The availability of validated outcome measures based on remission
      will enhance the conduct and reporting of clinical investigations, and could
      facilitate the design and interpretation of new studies on cognition and
      functional outcomes. While useful as a concept, it is important to consider that
      remission is distinct from recovery. CONCLUSION: The introduction of standardized
      remission criteria may offer significant opportunities for clinical practice,
      health services research and clinical trials.

PMID- 16423160
TI  - Non-affective Acute Remitting Psychosis: a preliminary report from Iran.
AB  - OBJECTIVE: To investigate the concept of 'Non-affective Acute Remitting
      Psychosis' (NARP) in a group of patients with first episode psychosis in Iran.
      METHOD: This is a 24-month follow-up study of 54 patients with first-episode
      psychosis admitted consecutively to a psychiatric hospital in Tehran, Iran. At
      the end of follow-up, consensus judgments were made on fulfillment of the NARP
      criteria as well as illness course and treatment. NARP was defined as a psychotic
      illness with acute onset (developed within 1 week), short duration (remission
      within 6 months), and the absence of prominent mood symptoms. RESULTS: Of 49
      patients who completed the follow-up, 15 (30.6%) had NARP, accounting for 60% of
      non-affective psychoses. Ten patients with NARP remained relapse free, four had a
      very short-lived relapse, and only one developed a chronic illness. Throughout
      the follow-up, patients with NARP received fewer months of treatment than did
      patients with other non-affective psychoses. CONCLUSION: The high proportion of
      NARP among patients with first episode psychosis, and the favorable course is in
      keeping with previous studies in developing countries.

PMID- 16423161
TI  - Neuropsychological functions predict 1- and 3-year outcome in first-episode
      psychosis.
AB  - OBJECTIVE: To examine neuropsychological performance as a possible predictor of
      course and outcome in first-episode psychotic (FEP) patients. METHOD: A group of
      consecutive FEP patients (n = 120) tested with Wechsler Adult Intelligence Scales
      Revised (WAIS-R) at baseline was compared with a healthy group (n = 30) matched
      for age, education and gender. Relationship between WAIS-R and both Brief
      Psychiatric Rating Scale and Global Assessment of Function (GAF) ratings were
      studied at baseline and at 1- and 3-year follow-ups. RESULTS: The performance of
      FEP patients was significantly lower (P < 0.001) than that of healthy comparison
      subjects on all WAIS-R subtests except for Information and Comprehension. The
      WAIS-R scores of patients with schizophrenia syndromes (DSM-IV) were lower than
      those of patients with non-schizophrenia syndromes on Block Design. Low WAIS-R
      Full-Scale IQ scores in FEP patients predicted the presence of negative symptoms
      at 1-year follow-up and of low GAF ratings at 3-year follow-up. CONCLUSION:
      Neurocognitive performance at admission appears to predict various aspects of
      functional outcome in FEP.

PMID- 16423162
TI  - Evidence for three distinct classes of 'typical', 'psychotic' and 'dual' mania:
      results from the EMBLEM study.
AB  - OBJECTIVE: To describe patients included in the European Mania in Bipolar
      Longitudinal Evaluation of Medication (EMBLEM) study and to assess and clinically
      validate the presence of clinical subtypes of patients with acute mania. METHOD:
      The EMBLEM study is a 2-year prospective, observational study on the treatment
      and outcome of patients who are treated for a manic or mixed episode. Latent
      Class Analysis was used to define discrete groups of patients at baseline.
      RESULTS: Three groups were identified: 'typical mania' (59% of patients);
      'psychotic mania' (27%) with more severe mania and presence of psychotic
      symptoms; and 'dual mania' (13%) with a high proportion of substance abuse.
      Patient groups differed in age of onset, social functioning and service needs.
      CONCLUSION: Dual mania represents a distinct and not infrequent subgroup of
      patients with mania. The exclusion of patients with comorbid substance problems
      from clinical trials creates a gap in our knowledge on treatment effectiveness.

PMID- 16423163
TI  - Homocysteine levels and glucose metabolism in non-obese, non-diabetic chronic
      schizophrenia.
AB  - OBJECTIVE: We studied a sample of schizophrenia out-patients to test the
      hypotheses that serum homocysteine concentrations would correlate positively with
      measures of glucose metabolism. METHOD: Subjects underwent a nutritional
      assessment and fasting plasma, serum insulin and homocysteine tests. RESULTS:
      Males had a significantly higher homocysteine levels than females (7.69 +/- 1.42
      microM vs. 6.63 +/- 1.40 microM; P = 0.02). Comparing subjects with normal
      fasting glucose (NFG) (glucose < 100 mg/dl) and impaired fasting glucose (IFG) (>
      or = 100 mg/dl) subjects with IFG (mean 8.2 +/- 1.5 microM) had significantly
      higher homocysteine levels than those with NFG (mean 7.2 +/- 1.4 microM, P =
      0.03). IFG was also associated with greater mean values for a Homeostatic Model
      Assessment-Insulin Resistance (HOMA-IR) (P = 0.002) and diastolic blood pressure
      (P = 0.045). CONCLUSION: The group with IFG had higher fasting serum homocysteine
      concentrations than those with NFG which supports a connection to an important
      cardiovascular risk factor.

PMID- 16423164
TI  - Maintenance antipsychotic medication patterns in outpatient schizophrenia
      patients: a naturalistic cohort study.
AB  - OBJECTIVE: Newer antipsychotics are increasingly used in schizophrenia
      maintenance. The UK change has been slow with little known on switching patterns.
      We aimed to investigate antipsychotic prescribing patterns in schizophrenia
      patients. METHOD: A naturalistic six-site cohort sample of 600 patients were
      interviewed by researchers at 6-monthly intervals for 2 years to record their
      clinical and social functioning; use of services and medication for the preceding
      6 months was obtained by structured extraction from clinical case notes. RESULTS:
      Alterations in antipsychotic medication were frequent in this group, mainly
      during periods of inpatient care. Atypical prescribing increased steadily, though
      slowly, across the period. Polypharmacy was less than anticipated. CONCLUSION:
      Inpatient care remains the main forum for switching of antipsychotics. The UK
      maintains a slow shift to atypical antipsychotics.

PMID- 16423165
TI  - Increased risk of extrapyramidal side-effect treatment associated with atypical
      antipsychotic polytherapy.
AB  - OBJECTIVE: To determine whether atypical antipsychotic polytherapy is a risk
      factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and
      whether the risk is attributable to antipsychotic dose. METHOD: We studied Iowa
      Medicaid beneficiaries aged 18-64 years with an active atypical and no
      conventional antipsychotic on January 1, 2001. The association of atypical
      antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple
      logistic regression was utilized to adjust for covariates in two models, the
      first adjusting for age, sex and the specific antipsychotic(s) prescribed, and
      the second also adjusting for doses. RESULTS: Among 4400 patients, the unadjusted
      odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy
      remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after
      adjusting for doses (OR 1.0, 95% CI 0.7-1.4). CONCLUSION: Atypical antipsychotic
      polytherapy is a risk factor for anti-EPS drug treatment, apparently because of
      higher cumulative doses.

PMID- 16423166
TI  - An exploratory open-label trial of aripiprazole as an adjuvant to clozapine
      therapy in chronic schizophrenia.
AB  - OBJECTIVE: We conducted this 6-week open-label trial to examine the effects of
      adjunctive aripiprazole in clozapine-treated subjects on weight, lipid and
      glucose metabolism, as well as positive and negative symptoms of schizophrenia.
      METHOD: Ten clozapine-treated subjects received aripiprazole augmentation; eight
      completed the 6-week trial and two ended at week 4. Eighty percent were male, the
      mean age was 38.7 +/- 8.9 years and the mean clozapine dose was 455 +/- 83 mg
      daily. RESULTS: There was a significant decrease in weight (P = 0.003), body mass
      index (P = 0.004), fasting total serum cholesterol (P = 0.002) and total
      triglycerides (P = 0.04) comparing baseline to study endpoint. There was no
      significant change in total Positive and Negative Syndrome Scale scores.
      CONCLUSION: This combination may be useful for clozapine-associated medical
      morbidity and must be studied in placebo-controlled double-blind randomized
      trials to determine efficacy and safety.

PMID- 16423167
TI  - Patients with schizophrenia treated with aripiprazole, a multicentre naturalistic
      study.
AB  - OBJECTIVE: The purpose was to carry out a naturalistic study on efficacy, safety
      and tolerability of aripiprazole during treatment of schizophrenia. Fifty-one
      patients with an ICD-10 diagnosis of schizophrenia and partial responders to
      prior antipsychotic medication were offered treatment with aripiprazole as
      monotherapy or in combination their prior medication. Inclusion criteria were
      lack of therapeutic effect or adverse events on former antipsychotic treatment.
      METHOD: Six-month open multicentre naturalistic study with prospective
      assessments including Body Mass Index (BMI), Clinical Global Impression-Severity
      (CGI-S), Clinical Global Impression-Improvement, Global Assessment of Functioning
      Scale (GAF) and adverse events. RESULTS: A statistically significant improvement
      in the different measures of psychopathology and global functioning (CGI-S
      reduction 34.7%; GAF improvement 14%) was shown in combination with a
      statistically significant reduction in BMI of 2.9%. Nine patients (17.6%) did not
      complete the 6-month treatment. CONCLUSION: In an open multicentre naturalistic
      study, aripiprazole showed to improve the severity of psychotic symptoms and the
      global level of functioning. However, many of the patients (47%) were also given
      another antipsychotic drug at the same time. Also, high compliance and few side
      effects were reported. However, because of the study design, the results must be
      interpreted conservatively.

PMID- 16423168
TI  - Multi-family treatment for patients with persistent auditory hallucinations and
      their relatives: a pilot study.
AB  - OBJECTIVE: To test feasibility and effectiveness of multi-family treatment (MFT)
      for patients with persistent auditory hallucinations. METHOD: A naturalistic
      pilot study with 6-month follow-up of 12 patients and 10 relatives. Pre- and post
      treatment assessment concerned compliance, satisfaction, subjective burden, and
      control of voices, psychopathology, quality of life, social functioning and
      burden on the family. RESULTS: Significant improvements were found in all
      domains. Compliance and satisfaction with treatment were satisfactory. Self-help
      contacts outside treatment sessions increased over time. CONCLUSION: MFT may be
      considered a potentially effective form of additional treatment for refractory
      voice hearers.

PMID- 16423172
TI  - Recombinant human erythropoietin: has treatment reached its full potential?
AB  - For more than 15 years recombinant human erythropoietin (r-HuEPO) has been used
      for the treatment of renal anemia benefiting patients with improved quality of
      life and reduced need for blood transfusions. It is still early in the history of
      r-HuEPO treatment; therapy has changed little and there have been few
      investigations into whether current treatment strategies are optimal. Of note,
      current therapy makes little attempt to mimic normal erythropoietin biology.
      Large doses of drug are administered episodically resulting in great fluxes in
      serum erythropoietin levels. It is unlikely that this approach is very efficient
      from the erythropoietic standpoint. Furthermore the effects of these nonbiologic
      kinetics on extraerythroid organs that express erythropoietin receptors are
      unknown. In this review the current state of r-HuEPO treatment is compared to the
      normal biology of erythropoietin and potential pitfalls caused by divergences are
      explored.

PMID- 16423173
TI  - Soliciting kidneys on web sites: is it fair?
AB  - The Internet serves as a meeting place where people in need of kidney transplants
      can find strangers willing to donate. While Good Samaritan donors located via the
      Internet increase the number of kidneys available for transplantation, they also
      raise ethical issues. This practice alters the pattern for distributing kidneys
      from unrelated living donors and raises questions of justice in the allocation of
      organs. It is unclear if commercial forces are at play in the arrangements made
      between potential donors and recipients via the Internet. While it is unfair that
      some recipients do not have suitable willing living donors, Web sites help to
      balance the inequity by increasing the opportunity to find a living donor; they
      also benefit other potential recipients by reducing the waiting list. However,
      although these Web sites are probably here to stay, Internet donor-recipient
      matches can have negative consequences that we need to minimize. Suggested
      strategies include regulated, monitored Web sites and the development of more
      anonymous organ donor programs.

PMID- 16423174
TI  - How should chronic medical therapies be altered with the onset of end-stage renal
      disease and initiation of dialysis?

PMID- 16423179
TI  - Diagnosis and management of insomnia in dialysis patients.
AB  - Sleep-related complaints affect 50-80% of patients on dialysis. Sleep disorders
      impair quality of life significantly. Increasing evidence suggests that sleep
      disruption has a profound impact both on an individual and on a societal level.
      The etiology of sleep disorders is often multifactorial: biologic, social, and
      psychological factors play a role. This is especially true for insomnia, which is
      the most common sleep disorder in different populations, including patients on
      dialysis. Biochemical and metabolic changes, lifestyle factors, depression,
      anxiety, and other underlying sleep disorders can all have an effect on the
      development and persistence of sleep disruption, leading to chronic insomnia.
      Insomnia is defined as difficulty initiating or maintaining sleep, or having
      nonrestorative sleep. It is also associated with daytime consequences, such as
      sleepiness and fatigue, and impaired daytime functioning. In most cases, the
      diagnosis of insomnia is based on the patient's history, but in some patients
      objective assessment of sleep pattern may be necessary. Optimally the treatment
      of insomnia involves the combination of both pharmacologic and nonpharmacologic
      approaches. In some cases acute insomnia resolves spontaneously, but if left
      untreated, it may lead to chronic sleep problems. The treatment of chronic
      insomnia is often challenging. There are only a few studies specifically
      addressing the management of this sleep disorder in patients with chronic renal
      disease. Considering the polypharmacy and altered metabolism in this patient
      population, treatment trials are clearly needed. This article reviews the
      diagnosis of sleep disorders with a focus on insomnia in patients on dialysis.

PMID- 16423180
TI  - Lipid abnormalities associated with end-stage renal disease.
AB  - Patients undergoing chronic renal replacement therapy have a high incidence of
      dyslipidemia. In general, there are increased concentrations of triglyceride-rich
      apolipoprotein B-containing particles. These elevations lead to increased levels
      of non-high-density lipoprotein (HDL) levels. This pattern is further modified by
      the method of dialysis (peritoneal versus hemodialysis) and comorbidities such as
      diabetes. End-stage renal disease patients also demonstrate increased levels of
      lipoprotein(a) (Lp(a)) and oxidized low-density lipoprotein (LDL)both of which
      are highly atherogenic. This review focuses on the pathogenesis of these lipid
      abnormalities and their role in the atherosclerotic process.

PMID- 16423181
TI  - Dialyzer reuse-Part I: Historical perspective.
AB  - The first apparatus for hemodialysis in animals, made painstakingly by Abel et
      al. in their laboratory at the beginning of 20th century, was cleaned with acid
      pepsin to digest blood, disinfected with thymol, and reused for up to 30
      experiments for as long as 8 months. The obvious incentive was saving time. In
      the early years of hemodialysis in patients, dialyzers and lines were assembled
      and sterilized immediately before dialysis. Various methods of dry and moist heat
      sterilization and miscellaneous chemical agents were employed for disinfection.
      Significant time was required to assemble the dialyzers, so there was an
      incentive to reuse previously assembled dialyzers to save time, especially for
      home hemodialysis. Bleach to clean and formaldehyde to disinfect the membranes
      and lines was used for this purpose. Preassembled dialyzers, commercially
      introduced in the 1950s, were the most expensive components of hemodialysis
      systems, therefore reprocessing of these dialyzers was the most effective way to
      save money. Refrigeration of coil dialyzers with blood, introduced in the mid
      1960s, was associated with frequent febrile reactions and was soon abandoned.
      Preassembled coil and plate dialyzers permitted almost complete return of blood
      after dialysis and led to the introduction of chemical disinfection for dialyzer
      reprocessing. A variety of disinfectants have been used. Formaldehyde was the
      most common disinfectant until the end of the 1970s. Sodium hypochlorite was used
      to clean the majority of dialyzers and to sterilize dialyzers with
      polyacrylonitrile membranes. In the early 1980s, peracetic acid and
      glutaraldehyde started to compete with formaldehyde. By the 1990s, formaldehyde
      had become less popular than peracetic acid. In the mid-1990s, disinfection and
      membrane cleaning with acetic acid and heat was introduced. Manual reprocessing
      was replaced by early reuse machines in the mid-1970s and a more sophisticated
      second generation of automated hemodialyzer reprocessing machines followed in the
      late 1970s. Recently disinfection of dialyzers with moist heat has resumed.
      Saving both time for the patient and money for the provider were the main
      motivations for designing a new machine for daily home hemodialysis. The machine,
      developed in the 1990s, cleans and moist-heat disinfects the dialyzer and lines
      in situ so they do not need to be changed for a month. In contrast, the reuse of
      dialyzers in home hemodialysis patients treated with other hemodialysis machines
      has become less popular and is almost extinct.

PMID- 16423182
TI  - Leptin and renal disease.
AB  - Leptin is a mediator of metabolism and disease in a variety of organ systems,
      most notably as an agent of energy stores. However, its role in renal disease as
      an inflammatory agent as well as its potential impact on the cachexia of uremia
      have sparked new interest in the molecule for nephrologists. This review
      elucidates the complex uremic state, the historical discovery of leptin and its
      physiology, and the potential interactions leptin has on both the progression of
      kidney disease as well as the morbidity and mortality of end-stage renal disease.

PMID- 16423183
TI  - Vascular calcifications in uremia: old concepts and new insights.
AB  - The annual mortality rate in uremic patients, corrected for age, sex, and race,
      is significantly higher than in the general population. This is primarily due to
      cardiovascular events. Vascular calcifications play a vital role in the
      development of cardiovascular morbidity and subsequent increased mortality.
      Vascular calcification affects both vascular intima and media layers and its
      mechanism remains poorly understood. Over the last few years it has been shown
      that, in addition to traditional cardiovascular risk factors, disturbances in
      mineral metabolism in the uremic milieu, calcium-containing phosphate binders,
      and vitamin D treatment of secondary hyperparathyroidism may contribute to the
      pathogenesis of vascular calcifications. Other uremia-related risk factors
      (e.g.increased oxidized low-density lipoprotein cholesterol, uremic toxins,
      increased oxidative stress, dialysis and dialysate-related factors, hemodynamic
      overload, hyperhomocysteinemia) may also play a role. In uremic patients, apart
      from these facilitating factors, decreased levels of endogenous calcification
      inhibitors such as fetuin-Amatrix Gla protein, osteoprotegerin, and osteopontin
      have also been associated with increased calcium-phosphate precipitation in
      extraskeletal tissues. Finally, vascular calcification is the outcome of the
      active and dynamic balance of procalcifying and anticalcifying influences. For
      the prevention and treatment of vascular calcifications, it is essential to avoid
      treatment modalities that lead to calcium overload, achieve good metabolic
      control, and optimize dialysis.

PMID- 16423184
TI  - Pulse high-volume hemofiltration in critically ill patients: a new approach for
      patients with septic shock.
AB  - Mortality rates in septic shock remain unacceptably high despite advances in our
      understanding of the syndrome and its treatment. Humoral factors are increasingly
      recognized to participate in the pathogenesis of septic shock, giving a
      biological rationale to therapies that might remove varied and potentially
      dangerous humoral mediators. While plasma water exchange in the form of
      hemofiltration can remove circulating cytokines in septic patients, the
      procedure, as routinely performed, does not have a substantial impact on their
      plasma levels. More intensive plasma water exchange, as high-volume
      hemofiltration (HVHF)can reduce levels of these mediators and potentially improve
      clinical outcomes. However, there are concerns about the feasibility and costs of
      HVHF as a continuous modality--very high volumes are difficult to maintain over
      24 hours and solute kinetics are not optimized by this regimen. We propose pulse
      HVHF (PHVHF)-HVHF of 85 ml/kg/hr for 6-8 hours followed by continuous venovenous
      hemofiltration (CVVH) of 35 ml/kg/hr for 16-18 hours-as a new method to combine
      the advantages of HVHFimprove solute kinetics, and minimize logistic problems. We
      treated 15 critically ill patients with severe sepsis and septic shock using
      daily PHVHF in order to evaluate the feasibility of the technique, its effects on
      hemodynamics, and the impact of the treatment on pathologic apoptosis in sepsis.
      Hemodynamic improvements were obtained after 6 hours of PHVHF and were maintained
      subsequently by standard CVVHas demonstrated by the reduction in norepinephrine
      dose. PHVHFbut not CVVHsignificantly reduces apoptotic plasma activity within 1
      hour and the pattern was maintained in the following hours. PHVHF appears to be a
      feasible modality that may provide the same or greater benefits as HVHFwhile
      reducing the workload and cost.

PMID- 16423187
TI  - Severe lactic acidosis treated with prolonged hemodialysis: recovery after
      massive overdoses of metformin.
AB  - We report two cases of severe lactic acidosis due to massive metformin ingestion.
      The first case was a 37-year-old man who was discovered several hours after
      ingesting 45 g of metformin. He had severe lactic acidosis (blood pH 6.81,
      bicarbonate 4 mEq/L, lactate 25.7 mEq/L). Despite intravenous bicarbonate
      therapy, he decompensated and was placed on a combination of hemodialysis and
      charcoal hemoperfusion for a continuous time of 25 hours. His hospital course was
      complicated by acute renal failure requiring a period of intermittent
      hemodialysis. He has since made a complete recovery. The second case was a 53
      year-old man who ingested 50 g of metformin. He also presented with severe lactic
      acidosis (blood pH 6.85, bicarbonate 3 mEq/L and lactate 28.4 mEq/L) and
      deteriorated despite intravenous bicarbonate therapy. He was placed on
      hemodialysis as a continuous therapy for 21 hours. His hospital course was
      complicated by acute renal failure requiring a period of intermittent
      hemodialysis. He has subsequently made a complete recovery. Metformin-associated
      lactic acidosis carries a high mortality rate. Prolonged hemodialysis should be
      considered as an early treatment option in these cases.

PMID- 16423185
TI  - Hip fractures in end-stage renal disease patients: incidence, risk factors, and
      prevention.
AB  - Hip fractures are an important problem for end-stage renal disease (ESRD)
      patients treated with dialysis. The incidence of hip fractures in the dialysis
      population is approximately four times that of the general population. Even more
      concerning is the associated 1 year mortality, which is twice that of other
      dialysis patients. Management of this problem is complicated by the heterogeneous
      nature of renal osteodystrophy and the inadequate methods of diagnosis currently
      available. Fall prevention has been shown to reduce the incidence of hip fracture
      and associated decline in functional ability in the general population. Because
      falls occur frequently in the dialysis population, simple fall prevention may be
      one important way of protecting dialysis patients from the morbidity and
      mortality of hip fracture.

PMID- 16423190
TI  - Detection of early arteriovenous fistula failure: systematic physical examination
      and beyond.

PMID- 16423188
TI  - Recent onset of focal arteriovenous graft swelling.

PMID- 16423191
TI  - Boning up on lanthanum.

PMID- 16423194
TI  - Editorial.

PMID- 16423195
TI  - Pleural disease: a forgotten frontier in respiratory research.

PMID- 16423196
TI  - Pulmonary arterial hypertension: new insights and new hope.
AB  - Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by
      abnormal increased vasoconstriction and vascular remodelling. In this review we
      discuss the pathophysiology, genetic basis and clinical features of this
      disorder. Current therapy of PAH is based on an understanding of its
      pathogenesis, and we review current treatment options based on the
      pathophysiology of the disease. We discuss three promising novel therapies
      studied in animal models and human tissue. All three therapies appear to prevent
      and reduce pulmonary arterial medial hyperplasia through their anti-proliferative
      and/or pro-apoptotic effects: serotonin transporter inhibitors by blocking
      serotonin uptake; dichloroacetate by activating voltage-gated potassium channels;
      and simvastatin by preventing activation of small GTPases.

PMID- 16423197
TI  - Involvement of PKC, p38 MAPK and AP-2 in IL-1beta-induced expression of
      cyclooxygenase-2 in human pulmonary epithelial cells.
AB  - OBJECTIVE: The aim of this study was to identify the signal molecules involved in
      IL-1beta-induced expression of cyclooxygenase (COX)-2 in human pulmonary
      epithelial (A549) cells. METHODS: A549 cells were stimulated with IL-1beta in the
      presence or absence of H-7 (a protein kinase C inhibitor), SB203580 (a p38
      mitogen-activated protein kinase inhibitor) and PD098059 (a mitogen-activated and
      extracellular regulated kinase kinase (MEK1) inhibitor). The A549 cells were also
      transfected with adenovirus vector encoding activator protein (AP)-2alpha, or a
      plasmid containing a dominant-negative gene (AP-2Delta), in the presence or
      absence of IL-1beta. RESULTS: IL-1beta induced expression of the COX-2 mRNA and
      protein in A549 cells in a time- and dose-dependent manner. SB203580 and H-7, but
      not PD098059, inhibited IL-1beta-induced expression of COX-2 protein.
      Overexpression of AP-2alpha increased expression of the COX-2 protein, whereas AP
      2Delta decreased IL-1beta-induced COX-2 expression. CONCLUSION: Protein kinase C,
      p38 mitogen-activated protein kinase and transcriptional factor AP-2alpha may
      play important roles in regulating IL-1beta-induced COX-2 expression in human
      pulmonary epithelial cells.

PMID- 16423198
TI  - Hypoxia-sensitive molecules may modulate the development of atherosclerosis in
      sleep apnoea syndrome.
AB  - OBJECTIVES: Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is associated
      with increased morbidity and mortality due to cardiovascular disease. In order to
      examine the association between OSAHS and cardiovascular disease, this study
      measured hypoxia-inducible and atherosclerosis-associated molecules in the
      peripheral blood. METHODS: In this study peripheral blood was obtained early in
      the morning from 60 consecutive male patients with OSAHS (AHI > or =10 events/h)
      and 30 male control subjects without OSAHS (AHI <5 events/h). Serum levels of
      heat shock protein-70 (Hsp-70), tissue factor (TF), monocyte chemotactic protein
      1 (MCP-1), highly sensitive C-reactive protein (hs-CRP), hepatocyte growth factor
      and plasma vascular endothelial growth factor were measured and their
      relationship with severity and hypoxaemia in OSAHS examined. RESULTS: Serum hs
      CRP, TF, MCP-1 and Hsp-70 levels were significantly higher in OSAHS compared with
      control subjects. Categorization of the patients into mild (10 < or = AHI < 30
      events/h), moderate (30 < or = AHI < 60 events/h) and severe (AHI > or = 60
      events/h) OSAHS subgroups showed that serum levels of hs-CRP, TF and Hsp-70
      increased with severity. The hs-CRP, TF, MCP-1 and Hsp-70 levels in the non-obese
      OSAHS group were also significantly higher than those in the control group
      whereas there was no difference in BMI between the two groups. Repetitive
      hypoxaemia significantly correlated with hs-CRP, TF and Hsp-70 levels and
      appeared to be a significant determinant for these molecules. CONCLUSIONS: These
      findings suggest that CRP, TF and Hsp-70 may be upregulated by repetitive
      hypoxaemia in OSAHS and may be involved in the development of the atherogenic
      process in OSAHS.

PMID- 16423200
TI  - Proteomic study of plasma proteins in pregnant women with asthma.
AB  - OBJECTIVE AND BACKGROUND: The course of asthma may be altered during pregnancy
      with at least one-third of women experiencing a worsening of asthma and 20%
      having an exacerbation during pregnancy. This study used the novel proteomic
      technique, surface-enhanced laser desorption ionization-time of flight mass
      spectrometry to determine if the presence of asthma during pregnancy was
      associated with alterations in plasma proteins. METHODS: Plasma collected from
      healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks
      gestation was applied to strong anion exchange (SAX2), weak cation exchange
      (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis
      was conducted using Ciphergen Protein Biology System IIc and significant
      differences in individual peak intensities between groups determined. RESULTS: At
      18 weeks gestation, 91 peaks were significantly different between pregnant women
      with and without asthma, representing 28% of the total peaks identified. At 30
      weeks gestation, 51 peaks were significantly different. There were two peaks that
      were significantly different between groups at both 18 and 30 weeks gestation and
      expressed at a similar level at both time points. One was increased in asthmatics
      (MW = 6444 Da) whereas the other decreased in asthmatics compared with non
      asthmatic women (MW = 1846 Da). CONCLUSIONS: This study demonstrated that there
      are differences in protein patterns between pregnant women with and without
      asthma. Other techniques are needed to define the molecular species and classify
      pathophysiological significance. Surface-enhanced laser desorption ionization
      time of flight mass spectrometry has potential as a tool to monitor disease
      progression in situations such as pregnancy.

PMID- 16423199
TI  - Anaerobic metabolism of inspiratory muscles in COPD.
AB  - OBJECTIVE: The purpose of this study was to determine if the respiratory muscles
      of patients with COPD could be made to function anaerobically, as evidenced by an
      increase in arterial blood lactate concentration ([lactate](a)) during specific
      loading of the inspiratory muscles and, if so, the effect of a programme of high
      intensity inspiratory muscle training on this function. METHODS: In seven
      patients with COPD (FEV(1) = 33 +/- 14% of predicted), measurements of
      [lactate](a) were made each minute during progressive inspiratory threshold
      loading to voluntary exhaustion. These tests were performed before and after an 8
      week programme of specific high-intensity inspiratory muscle training, combined
      with general whole-body exercise training. RESULTS: During inspiratory muscle
      loading small increases in [lactate](a) (0.83 +/- 0.32 mM) were observed in two
      subjects before training, and in five subjects after training (0.69 +/- 0.57 mM).
      [Lactate](a) only increased when the inspiratory work rate exceeded 6.9 cm H(2)O
      L/min per kilogram of body weight, and when baseline maximum inspiratory pressure
      exceeded 65 cm H(2)O. CONCLUSIONS: The results of this study demonstrated that it
      is possible for COPD patients to increase inspiratory muscle work rate to a level
      requiring a major energy contribution from anaerobic glycolytic metabolism. This
      was only seen when inspiratory muscle strength and endurance were sufficient to
      allow it. Some patients who failed to demonstrate an increase in [lactate](a) at
      baseline did so after a programme of high-intensity inspiratory muscle training.

PMID- 16423201
TI  - Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and
      their clinical significance.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly discovered
      disease caused by a novel coronavirus. The present study studied the longitudinal
      profile of antibodies against SARS-coronavirus (SARS-CoV) in SARS patients and
      evaluated the clinical significance of these antibodies. METHODS: Two methods,
      ELISA and indirect immunofluorescent assay, were used for the detection of the
      anti-SARS-CoV IgG and IgM in 335 serial sera from 98 SARS patients. In 18
      patients, serum antibody profiles were investigated and antibody neutralization
      tests were performed from 7 to 720 days after the onset of symptoms. RESULTS: The
      ratios of positive IgG/IgM by ELISA were 0/0, 45.4/39.4, 88.6/71.4, 96/88,
      100/48.6, 100/30.9, 100/17.1, 100/0 per cent, respectively, on 1-7, 8-14, 15-21,
      22-28, 29-60, 61-90, 91-180 and 181-720 days after the onset of symptoms.
      Antibodies were not detected within the first 7 days of illness, but IgG titre
      increased dramatically on day 15, reaching a peak on day 60, and remained high
      until day 180 from when it declined gradually until day 720. IgM was detected on
      day 15 and rapidly reached a peak, then declined gradually until it was
      undetectable on day 180. Neutralizing viral antibodies were demonstrated in the
      convalescence sera from SARS patients. CONCLUSION: The persistence of detectable
      IgG antibodies and neutralizing viral antibodies for up to 720 days suggest that
      SARS patients may be protected from recurrent SARS-CoV infection for up to 2
      years.

PMID- 16423203
TI  - Effect of simulated altitude during sleep on moderate-severity OSA.
AB  - OBJECTIVE: These studies were conducted to test the hypothesis that isobaric
      hypoxia would switch OSA to central sleep apnoea (CSA). METHODS: Five adult men
      (mean age 54.2 +/- 5.5 years, mean BMI 29.9 +/- 6.7 kg/m(2)) with moderate OSA
      underwent overnight polysomnography at three altitudes. The highest altitude was
      simulated in a normobaric hypoxic chamber. RESULTS: The obstructive respiratory
      disturbance index fell from 25.5 +/- 14.4/h at 60 m to 17.3 +/- 9.2/h at 610 m
      and 0.5 +/- 0.7/h at 2750 m (P = 0.004 compared with 60 m). The central
      respiratory disturbance index rose from 0.4 +/- 0.5/h at 60 m to 8.1 +/- 5.8/h at
      610 m and 78.8 +/- 29.7/h at 2750 m (P < 0.001 compared with 60 m). Mean sleep
      SaO(2) fell from 94 +/- 1% at 60 m to 93 +/- 1% at 610 m to 85 +/- 4% at 2750 m
      (P < 0.001 compared with 60 m). CONCLUSION: Moderate severity OSA at sea level
      (60 m) was completely replaced by severe CSA at a simulated altitude of 2750 m.
      The authors believe that the OSA resolved because of an increased respiratory
      drive [corrected] and an increase in upper airway tone, whereas CSA developed
      because of hypocapnia in non-rapid eye movement sleep.

PMID- 16423202
TI  - Inflammatory subtypes in asthma: assessment and identification using induced
      sputum.
AB  - OBJECTIVE: The authors sought to investigate the detection of non-eosinophilic
      asthma using induced sputum. Although this is an important subtype of clinical
      asthma, its recognition is not standardized. METHODS: Adult non-smokers with
      asthma and healthy controls underwent sputum induction and hypertonic saline
      challenge. Non-eosinophilic asthma was defined as symptomatic asthma with normal
      sputum eosinophil counts. The normal range for sputum eosinophil count was
      determined using the 95th percentile from the healthy control group as a cut-off
      point. RESULTS: The recognition of non-eosinophilic asthma using eosinophil
      proportion was in agreement with a definition based on absolute eosinophil count
      (kappa 0.67). Non-eosinophilic asthma was a stable subtype over both the short
      term (4 weeks) and longer term (5 years, kappa 0.77). Airway inflammation in
      asthma could be categorized into four inflammatory subtypes based on sputum
      eosinophil and neutrophil proportions. These subtypes were neutrophilic asthma,
      eosinophilic asthma, mixed granulocytic asthma and paucigranulocytic asthma.
      Subjects with increased neutrophils (neutrophilic asthma and mixed granulocytic
      asthma) were older and had an increased total cell count and cell viability
      compared with other subtypes. CONCLUSION: Induced sputum eosinophil proportion is
      a good discriminator for eosinophilic asthma, providing a reproducible definition
      of a homogenous group. The remaining non-eosinophilic subjects are heterogeneous
      and can be further classified based on the presence of neutrophils. These
      inflammatory subtypes have important implications for the investigation and
      characterization of airway inflammation in asthma.

PMID- 16423204
TI  - High plasma levels of factor VIII: an important risk factor for isolated
      pulmonary embolism.
AB  - OBJECTIVE: The aim of the study was to investigate whether factor V Leiden and
      prothrombin G20210A mutations, elevated levels of factor VIII and factor IX are
      associated with pulmonary embolism (PE). METHODS: Sixty-four patients with
      objectively documented PE and 64 control subjects were included in this study.
      The authors divided the 64 subjects with PE into those with PE and deep vein
      thrombosis (combined form of venous thromboembolism, n = 26) and those with PE
      without deep vein thrombosis (isolated PE n = 38). RESULTS: There was no
      significant difference between the PE groups and the control subjects with regard
      to the presence of factor V Leiden and prothrombin mutations and elevated levels
      of factor IX. Using the 90th percentile measured in control subjects (P(90) = 168
      U/dL) as a cut-off point for factor VIII levels, the authors found an 11-fold
      increased risk for both isolated PE patients and patients with a combined form of
      venous thromboembolism who have factor VIII levels >168 U/dL compared with
      individuals having factor VIII levels below this cut-off point. The risk was not
      affected by adjustments for other possible risk factors. CONCLUSIONS: Elevated
      plasma factor VIII levels were found to be a significant, independent risk factor
      for PE.

PMID- 16423205
TI  - Recent air travel and venous thromboembolism resulting in hospital admission.
AB  - OBJECTIVE: The objective of the study was to determine the proportion of patients
      admitted to hospital with a deep vein thrombosis (DVT) or pulmonary embolism (PE)
      in whom recent air travel was documented in the medical records. METHODS: A
      retrospective review of the medical records of patients with a primary or
      secondary discharge diagnosis of DVT or PE in four hospitals in New Zealand was
      undertaken. From the medical records information was collected on demographic
      details, documentation of the presence of risk factors and results of
      radiological investigations. Strict radiological criteria were applied to ensure
      that the diagnosis of DVT or PE was firmly established. RESULTS: In 60 of 576
      (10.4%) patients with a confirmed venous thromboembolism there was documentation
      of recent air travel; in 31 of these 60 subjects no other risk factors were
      recorded. In those cases in whom details of the air travel had been recorded, it
      had been undertaken in the previous 1 week in 65.0%, and in 43.3% the air travel
      was of at least 10-h duration. CONCLUSION: Long distance air travel is an
      important risk factor for venous thromboembolism requiring hospital admission and
      represents a significant public health problem in New Zealand.

PMID- 16423206
TI  - Simkania negevensis and newly diagnosed asthma: a case-control study in 1- to 6
      year-old children.
AB  - BACKGROUND: Simkania negevensis is an intracellular bacterium, sharing many
      characteristics with Chlamydophila and Chlamydia species. S. negevensis infection
      has been associated with bronchiolitis in infants and with pneumonia and
      exacerbations of COPD in adults. OBJECTIVE: The aim of the present study was to
      evaluate, in a case-control setting, whether S. negevensis serology had any
      association with the onset of asthma in children. METHODS: S. negevensis-specific
      IgM, IgA and IgG antibodies were measured by microimmunofluorescence in 104
      children below school-age with newly diagnosed asthma, and in 122 control
      children. RESULTS: S. negevensis-specific IgM was detected in two (2%) cases and
      in nine (8%) of the controls. IgG was detected in 12 (12%) cases and 12 (10%) of
      the controls. IgA antibodies were absent in all children. The age distribution of
      the 35 children with S. negevensis-specific antibodies was even, the positivity
      rate being 11% in the 12- to 23-month-old group and 20-23% in the children aged
      between 2 and 5 years. CONCLUSION: Although S. negevensis appears to cause
      infections in the Finnish preschool-aged population, there was no association
      with asthma.

PMID- 16423207
TI  - Positron emission tomography with CT in the evaluation of non-small cell lung
      cancer in populations with a high prevalence of tuberculosis.
AB  - OBJECTIVE AND BACKGROUND: To determine the utility of positron emission
      tomography with CT (PET-CT) in the evaluation of non-small cell lung cancer
      (NSCLC) in an Asian context where tuberculosis rates are moderately high.
      METHODS: Case records of consecutive patients with NSCLC undergoing PET-CT at the
      Singapore General Hospital over a 1-year period were retrospectively reviewed.
      The authors evaluated the sensitivity and specificity of PET-CT at their
      institution using surgical pathology or the tincture of time as the gold
      standard. RESULTS: A total of 54 patients underwent PET-CT during this period.
      Seven patients were evaluated for solitary pulmonary nodule, for which PET-CT
      gave a sensitivity of 100% and specificity of 75%. There was one patient with
      false positive PET-CT due to active tuberculosis. In total, 41 patients underwent
      PET-CT for staging of NSCLC. There was one false positive (patient was found to
      have active tuberculous lymphadenitis) and one false negative for NSCLC. This
      gave a sensitivity of 92.3% and a specificity of 95%. Histology from the adrenal
      glands was available in two patients with PET-CT that was positive for adrenal
      metastases. One proved to be benign whereas the other was consistent with
      metastasis. Two patients had PET-CT positive for liver metastases, which was
      verified by histology. Two patients with positive PET-CT for lesions in the colon
      turned out to be benign histologically. CONCLUSIONS: Positron emission tomography
      with CT for the evaluation and follow-up of solitary pulmonary nodule and NSCLC
      can provide additional useful information to conventional radiology for treatment
      planning and a non-invasive determination of prognosis. However, physicians need
      to be aware of the limitations of this imaging modality, particularly when
      tuberculosis has a high prevalence in the population.

PMID- 16423208
TI  - Intrapleural cisplatin and OK432 therapy for malignant pleural effusion caused by
      non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate the efficacy of combined intrapleural therapy with
      cisplatin, an antineoplastic agent, and OK432, a sclerosing agent, in controlling
      malignant pleural effusions, when compared with monotherapy with either agent.
      METHODS: A total of 49 non-small cell lung cancer patients with malignant pleural
      effusion were randomly assigned to one of three groups: intrapleural cisplatin
      therapy (n = 17), intrapleural OK432 therapy (n = 17), or both (n = 15). They
      were compared in terms of success rate, duration of indwelling chest tube and
      adverse reactions. RESULTS: Rates of pleural effusion recurrence within 180 days
      following cisplatin, OK432, or combination therapy were 64.7%, 52.9% and 13.3%,
      respectively, being significantly lower in the combination therapy group (P =
      0.01). The mean duration of chest tube drainage was 8.4 days, 5.5 days and 12.9
      days, respectively, being significantly longer in the combination therapy group
      (P < 0.001). All procedures were well tolerated. CONCLUSIONS: Although chest tube
      drainage took longer because of the time required for multiple administration of
      the agents, intrapleural combination therapy with cisplatin and OK432 was more
      effective in controlling malignant pleural effusions due to non-small cell lung
      cancer than monotherapy with either agent.

PMID- 16423209
TI  - Maintaining exercise capacity and quality of life following pulmonary
      rehabilitation.
AB  - OBJECTIVE: The optimum method for sustaining the benefits gained from pulmonary
      rehabilitation (PR) has not been determined. In this report the authors describe
      the 4-year referral and uptake patterns to a hospital-based outpatient PR
      programme, and the sustained benefits of PR in patients with COPD attending a
      community-based maintenance exercise programme. METHODS: Entry and exit data were
      mapped for all patients referred to the PR service over the review period. All
      eligible patients were offered a community-based maintenance exercise programme
      upon completion of PR. A total of 21 patients underwent follow-up assessment of
      functional exercise capacity, quality of life (QOL) and health-care utilization.
      RESULTS: Over a 4-year period, 467 patients (80% with COPD) were referred to the
      programme, of whom 230 entered PR. In total, 172 patients completed PR, with
      attrition (25%) being mostly due to medical problems. Of the 84 patients who
      elected for the community-based programme, 46 were still attending at follow up
      and 21 patients with moderate-to-severe COPD (44.9 +/- 12.6 (mean +/- SD) FEV(1)%
      predicted) were reassessed at 18.4 +/- 11.9 months post PR. Significant
      improvements (mean change (95% confidence interval)) persisted in 6-min walk
      distance (41.1 m (15.7-66.5)), distance walked in 20 min (195.1 m (82.3-308)) and
      in QOL (Chronic Respiratory Disease Questionnaire) (11.0 points (4.4-17.6)) (P <
      0.01). The QOL improvements exceeded the minimum clinically important difference.
      A trend towards a reduction in COPD-related hospital admissions, bed-days and
      emergency department presentations was observed in the 12 months following PR.
      Self-reported adherence with the home exercise programme indicated that 67% of
      patients were exercising at least 3-5 days each week in addition to attending a
      class. CONCLUSION: For patients with moderate-to-severe COPD, a weekly community
      based maintenance exercise class, supervised by a physiotherapist, combined with
      a home exercise programme is an effective intervention for maintaining
      improvements following PR.

PMID- 16423210
TI  - Efficacy and safety of iodopovidone pleurodesis through tube thoracostomy.
AB  - OBJECTIVE: To evaluate the efficacy and safety of iodopovidone as an agent for
      pleurodesis through tube thoracostomy in patients with recurrent pleural
      effusions and pneumothorax. METHODS: This was a prospective study in which
      pleurodesis was performed with a solution of 20 mL 10% iodopovidone and 80 mL
      normal saline solution infused through a tube thoracostomy and left in the
      pleural cavity for 4 h. RESULTS: A total of 64 patients (34 men) with a mean (+/
      SD) age of 47.1 +/- 15.4 years were included. There were 37 cases of pleural
      effusion and 27 of pneumothorax. A complete response (neither reaccumulation of
      fluid nor recurrence of pneumothorax) was obtained in 32 (86.5%) patients with
      pleural effusion and 25 (92.6%) patients with pneumothorax. A second procedure
      (i.e. repeated pleurodesis) was attempted successfully in four patients in the
      pleural effusion group. All patients experienced chest pain to a varying degree
      as recorded on a Visual Analogue Scale (median 50.5, range 10-95). Seven patients
      developed fever and one immunocompromised patient developed empyema following the
      procedure. There were no recurrences at a median follow up of 5 months (range 3
      15 months) in the pleural effusion group, and 13 months (range 6-24 months) in
      the pneumothorax group. CONCLUSIONS: Iodopovidone can be used as an effective and
      safe agent for (chemical) pleurodesis (through tube thoracostomy), which is
      inexpensive and readily available.

PMID- 16423211
TI  - Multiple tracheobronchial mucosal lesions in two cases of Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is characterized by hypereosinophilia and a systemic
      necrotizing vasculitis seen almost exclusively in patients with asthma. The most
      common pathological findings in the chest in CSS are eosinophilic pneumonia,
      necrotizing vasculitis and granulomatous inflammation (extravascular granuloma).
      However, tracheobronchial mucosal lesions have rarely been reported in CSS. The
      authors report two patients with CSS who had multiple tracheobronchial mucosal
      lesions that were found by fibreoptic bronchoscopy. They were tiny nodular
      lesions and necrotizing bronchial inflammation with many eosinophils was observed
      upon pathological examination. The authors concluded that tracheobronchial
      mucosal lesions may be one of the manifestations of vasculitis seen in CSS.

PMID- 16423212
TI  - Gefitinib-induced lung injury successfully treated with high-dose
      corticosteroids.
AB  - A 55-year-old man was treated with gefitinib for disseminated pleural lesions, 1
      year after resection of the left lower lobe for non-small cell lung cancer. After
      6 weeks of continuous daily treatment with oral gefitinib, he developed dyspnoea
      on exertion and a non-productive cough. CXR and CT revealed focal areas of ground
      glass opacity (GGO) in the right upper lobe. Despite gefitinib being
      discontinued, high-resolution CT revealed extension of GGO and restructuring of
      lung parenchyma, suggesting acute interstitial pneumonia. Transbronchial biopsy
      revealed acute-phase diffuse alveolar damage. After administration of
      methylprednisolone pulse therapy (1 g/day intravenously) for three consecutive
      days, the areas of GGO shrank on high-resolution CT and symptoms resolved.
      Diffuse alveolar damage caused by gefitinib can be successfully treated in the
      early phase with high-dose corticosteroids. Patients receiving gefitinib should
      be carefully examined for symptoms and undergo CT if their condition
      deteriorates.

PMID- 16423213
TI  - CT bronchoscopy in the diagnosis of Williams-Campbell syndrome.
AB  - Williams-Campbell syndrome, a rare disorder, is characterized by a congenital
      deficiency of cartilage, typically involving the fourth to the sixth order
      bronchi, and resulting in expiratory airway collapse and bronchiectasis. The
      authors report a patient with Williams-Campbell syndrome with type II respiratory
      failure due to extensive cystic bronchiectasis and secondary emphysema. CT of the
      thorax showed the affected bronchi had characteristic ballooning on inspiration
      and collapse on expiration. Three-dimensional images of the tracheobronchial tree
      were constructed from a volume of data acquired by thin-slice CT scanning. Apart
      from confirming expiratory collapse of the affected bronchi, these images
      revealed an absence of the cartilage ring impressions in the bronchial wall,
      extending bilaterally from the mainstem down to subsegmental bronchi, suggesting
      cartilage deficiency.

PMID- 16423214
TI  - Hepatopulmonary syndrome can show spontaneous resolution: possible mechanism of
      portopulmonary hypertension overlap?
AB  - Hepatopulmonary syndrome (HPS) (hypoxaemia due to intrapulmonary vasodilation and
      a right-to-left shunt associated with liver disease) resolves after liver
      transplantation. The authors describe a case of spontaneous resolution of HPS
      prior to liver transplantation. This patient was diagnosed with HPS associated
      with extra-hepatic biliary atresia when she was 10 years old. She exhibited
      digital clubbing, facial vascular dilation, cyanosis, and suffered from dyspnoea
      during exercise. The patient's PaO(2) at rest was 53.8 mm Hg in room air and a
      Technetium-99m macro-aggregated albumin lung perfusion scan demonstrated a right
      to-left shunt. Although her symptoms and laboratory data supported a diagnosis of
      HPS, she nevertheless showed spontaneous resolution within 2 years. When she was
      14 years old, pulmonary hypertension was evident upon examination of her
      echocardiogram. HPS may be improved or masked by an accidental overlap with
      pulmonary hypertension in the terminal stage of liver disease.

PMID- 16423215
TI  - A year in review: Respirology 2005 - clinical science.

PMID- 16423216
TI  - Facial soft tissue thicknesses in Australian adult cadavers.
AB  - Craniofacial identification methods heavily rely on the knowledge of average soft
      tissue depths. This study measured soft tissue thicknesses of an Australian
      cadaver sample (N = 33) using published needle puncture techniques at 13
      anatomical locations. Data were compared and contrasted with other studies that
      used essentially identical samples and methods. Full descriptive statistics were
      calculated for measurements made in this study and means, medians, and modes were
      reported. Differences between mean values for males and females were found to be
      minimal (2.2 mm or less) and considerable overlap was found between the groups.
      There were no statistically significant differences between the soft tissue
      depths of the sexes (P>0.05). These findings indicate that differences between
      male and female soft tissue depths are of little practical significance for
      craniofacial identification and, therefore, data (means, standard deviations, and
      sample sizes) reported for Australians were pooled across the sexes and the
      studies. Although these new pooled means have increased statistical power, data
      distributions at some landmarks were skewed and thus emphasis is placed on median
      and modes reported for this study rather than upon the collapsed data means.

PMID- 16423217
TI  - The effects of chemical and heat maceration techniques on the recovery of nuclear
      and mitochondrial DNA from bone.
AB  - Forensic anthropologists use a number of maceration techniques to facilitate
      skeletal analysis of personal identity and trauma, but they may unwittingly
      eliminate valuable DNA evidence in the process. This study evaluated the effect
      of 10 maceration methods on gross bone structure and the preservation of DNA in
      ribs of 12 pigs (Sus scrofa). A scoring system was applied to evaluate the ease
      of maceration and resulting bone quality while DNA purity was quantified by
      optical densitometry analysis, followed by polymerase chain reaction (PCR)
      amplification of three mitochondrial and three nuclear loci. The results
      demonstrated that while mitochondrial DNA could be amplified for all experiments,
      cleaning treatments using bleach, hydrogen peroxide, ethylenediaminetetraacetic
      acid/papain, room temperature water and detergent/sodium carbonate followed by
      degreasing had low DNA concentrations and failed to generate nuclear PCR
      products. In general, treatments performed at high temperatures (90 degrees C or
      above) for short durations performed best. This study shows that traditionally
      "conservative" maceration techniques are not necessarily the best methods to
      yield DNA from skeletal tissue.

PMID- 16423218
TI  - A parameter study regarding the IBIS correlator.
AB  - The electronic system IBIS has been used by numerous agencies worldwide as the
      standard tool to compare firearm markings on bullets and fired cartridges. There
      is a general interest among users concerning the likelihood with which the IBIS
      correlator may locate hits in its databases. Test results of the performance
      under different test conditions have been published in various papers. Experience
      has also been gained with the IBIS system from years of practical usage. All of
      these findings are difficult to compare with each other. No systematic
      presentation exists that actually shows the parameters upon which the success
      rate of the IBIS correlator depends. There has also been no mention of what
      values these parameters take on during each test. This paper first generally
      defines the success and error rates of the IBIS correlator. The parameters used
      will be discussed. Results of previously published tests will be re-examined
      based on this methodology. An illustrative form of presentation for the success
      rate of an electronic comparison system will also be suggested. It will be shown
      that the success rate of the IBIS correlator highly depends on the quality of the
      firearms-generated markings. It increases with the number of considered mark
      types, the number of available signatures per firearm, and the number of items
      inspected in the hit list. The success rate decreases with the database size. The
      paper will conclude with a series of practical recommendations for the setting up
      and successful operation of an electronic collection of ballistic evidence.

PMID- 16423219
TI  - An experience report regarding the performance of the IBIS correlator.
AB  - The majority of published experimental evaluations of the performance of the IBIS
      system are based on very specific conditions, mainly considering IBIS as a tool
      to create a "ballistic database." No recent reports were found covering the
      performance of the IBIS system to search an open case file of realistic
      structure. In this paper, the performance of the IBIS correlator will be
      evaluated, based on four different data sources that predominantly concern the
      operation of the central collection of evidence ammunition of the Federal
      Criminal Police Office (BKA), Germany. The results allow a conclusion on the
      success and error rates to be expected of the IBIS correlator in a realistic
      OCFDB ("open case file database") environment, given certain conditions. It was
      found that success rates of 75-95% for cartridge case comparisons and 50-75% for
      bullet comparisons can be achieved in practice. Recommendations for a most
      efficient way to operate the IBIS electronic comparison system will be presented
      based on the results of the evaluations. The terms and definitions in this report
      completely correspond with the definitions in an earlier article. Familiarity
      with this article is therefore absolutely necessary to fully understand many of
      the statements presented here.

PMID- 16423220
TI  - Identification of Acer rubrum using amplified fragment length polymorphism.
AB  - Amplified fragment length polymorphism (AFLP) analysis of botanical forensic
      evidence provides a means of obtaining a reproducible DNA profile in a relatively
      short period of time in species for which no sequence information is available.
      AFLP profiles were obtained for 40 Acer rubrum trees. Leaf material from five
      additional species was also typed. Genomic DNA was isolated using the DNeasy
      Plant Miniprep Kit (Qiagen, Valencia, CA), double-digested by two restriction
      endonucleases (EcoRI and MseI) and ligated to oligonucleotide adapters. Two
      consecutive PCR reactions (pre-amplification and selective amplification) were
      performed using a modification of the AFLP protocol described by Gibco
      (Invitrogen, Rockville, MD). The DNA fragments were separated by capillary
      electrophoresis using the CEQ 8000 DNA Fragment Analyzer. A number of Acer rubrum
      species-specific peaks were identified. In addition, within this closed set of
      samples, 15 of 16 (93.8%) blind samples were correctly identified. AFLP data can
      be used to determine the species of botanical evidence or to associate a sample
      to a source. This information can be used in forensic investigations to link a
      piece of evidence with a particular location or suspect.

PMID- 16423221
TI  - Analysis of carbohydrates in seized heroin using capillary electrophoresis.
AB  - Illicitly produced heroin is commonly cut with carbohydrates to increase bulk.
      The analysis of these solutes is important for legal and intelligence purposes. A
      capillary electrophoresis (CE) method was developed for the qualitative analysis
      of dextrose, lactose, sucrose, inositol, and mannitol in heroin exhibits. For
      this method, a 64 cm (55.5 cm to detector window) by 50 mum capillary was used
      with the Agilent Basic Anion Buffer modified to pH 12.1. This separation was
      performed at 25 degrees C with a voltage of 20 kV and indirect detection with 2,6
      pyridinedicarboxylic acid as the visualization reagent. The methodology is also
      applicable for the screening of inorganic and organic anions using indirect
      detection, and acidic adulterants using direct detection. For a run time of 13
      min, the relative standard deviation (n = 6) of the methodology was better than
      0.36% for migration times and less than 2.6% for corrected peak areas. For the
      analysis of carbohydrates and acidic adulterants in seized heroin, excellent
      agreement was obtained between CE and nuclear magnetic resonance spectroscopy.

PMID- 16423222
TI  - The determination of psilocin and psilocybin in hallucinogenic mushrooms by HPLC
      utilizing a dual reagent acidic potassium permanganate and tris(2,2'
      bipyridyl)ruthenium(II) chemiluminescence detection system.
AB  - This paper describes a procedure for the determination of psilocin and psilocybin
      in mushroom extracts using high-performance liquid chromatography with postcolumn
      chemiluminescence detection. A number of extraction methods for psilocin and
      psilocybin in hallucinogenic mushrooms were investigated, with a simple
      methanolic extraction being found to be most effective. Psilocin and psilocybin
      were extracted from a variety of hallucinogenic mushrooms using methanol. The
      analytes were separated on a C12 column using a (95:5% v/v) methanol:10 mM
      ammonium formate, pH 3.5 mobile phase with a run time of 5 min. Detection was
      realized through a dual reagent chemiluminescence detection system of acidic
      potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II). The
      chemiluminescence detection system gave improved detectability when compared with
      UV absorption at 269 nm, with detection limits of 1.2 x 10(-8) and 3.5 x 10(-9)
      mol/L being obtained for psilocin and psilocybin, respectively. The procedure was
      applied to the determination of psilocin and psilocybin in three Australian
      species of hallucinogenic mushroom.

PMID- 16423223
TI  - Species identification of Kachuga tecta using the cytochrome b gene.
AB  - A DNA technique has been established for the identification to species level of
      tortoises. The test on the shell of the animal was used to identify samples from
      the species Kachuga tecta. A total of 100 tortoise shell specimens collected from
      the National Council of Agriculture (COA), Taiwan, were used in this study.
      Primer pairs were designed to amplify partial DNA fragments of cytochrome b
      within the mitochondrial genome. The DNA data showed that among the 100 samples,
      there were four distinct haplotype DNA sequences, within which there were a total
      of 90 variable sites. Between haplotypes I and II, there was only 1 nucleotide
      difference at position 228. Between haplotypes I and III, 65 nucleotide
      differences were observed; haplotypes I and IV, 62 nucleotide differences; and
      haplotypes III and IV, 56 nucleotide differences were observed. There were 66 and
      63 nucleotide differences between haplotypes II and III and haplotypes II and IV
      respectively. All four haplotypes were compared with the DNA sequences held at
      the GenBank and EMBL databases. The most similar species were K. tecta (haplotype
      I and II), Morenia ocellata (haplotype III) and Geoclemys hamiltonii (haplotype
      IV), and their respective mtDNA similarities were 99.5%, 99.3%, 89.9% and 99.5%.
      However, as haplotype III was only 89.9% homologous with M. ocellata, it would
      seem that this haplotype shows only a limited relationship with a similar species
      registered currently in these databases. The method established by this study is
      an additional method for the identification of samples protected under Convention
      International Trade in Endangered Species (CITES) and will improve the work for
      the preservation of the endangered species.

PMID- 16423224
TI  - Detection of visible and latent fingerprints using micro-X-ray fluorescence
      elemental imaging.
AB  - Using micro-X-ray fluorescence (MXRF), a novel means of detecting fingerprints
      was examined in which the prints were imaged based on their elemental
      composition. MXRF is a nondestructive technique. Although this method requires a
      priori knowledge about the approximate location of a print, it offers a new and
      complementary means for detecting fingerprints that are also left pristine for
      further analysis (including potential DNA extraction) or archiving purposes.
      Sebaceous fingerprints and those made after perspiring were detected based on
      elements such as potassium and chlorine present in the print residue. Unique
      prints were also detected including those containing lotion, saliva, banana, or
      sunscreen. This proof-of-concept study demonstrates the potential for visualizing
      fingerprints by MXRF on surfaces that can be problematic using current methods.

PMID- 16423225
TI  - Development and validation of the AmpFlSTR Yfiler PCR amplification kit: a male
      specific, single amplification 17 Y-STR multiplex system.
AB  - In the past 5 years, there has been a substantial increase in the use of Y-short
      tandem repeat loci (Y-STRs) in forensic laboratories, especially in cases where
      typing autosomal STRs has met with limited success. The AmpFlSTR Yfiler PCR
      amplification kit simultaneously amplifies 17 Y-STR loci including the loci in
      the "European minimal haplotype" (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390,
      DYS391, DYS392, and DYS393), the Scientific Working Group on DNA Analysis Methods
      (SWGDAM) recommended Y-STR loci (DYS438 and DYS439), and the highly polymorphic
      loci DYS437, DYS448, DYS456, DYS458, Y GATA H4, and DYS635 (formerly known as Y
      GATA C4). The Yfiler kit was validated according to the FBI/National Standards
      and SWGDAM guidelines. Our results showed that full profiles are attainable with
      low levels of male DNA (below 125 pg) and that under optimized conditions, no
      detectable cross-reactive products were obtained on human female DNA, bacteria,
      and commonly encountered animal species. Additionally, we demonstrated the
      ability to detect male specific profiles in admixed male and female blood samples
      at a ratio of 1:1000.

PMID- 16423226
TI  - Quantitation of human genomic DNA through amplification of the amelogenin locus.
AB  - An alternate method for quantitation of human genomic DNA is presented.
      Quantitative template amplification technology (abbreviated "Q-TAT") estimates
      the quantity of human DNA present in an extract by comparing fluorescence in X
      and Y amplicons produced from unknowns with fluorescence in a standard curve
      amplified from known quantities of reference DNA. Q-TAT utilizes PCR and
      electrophoresis with fluorescent detection/quantitation, precluding the need for
      new instrumentation, methodology, or quality assurance associated with slot-blot
      or real-time PCR. In a comparison study incorporating shared samples, Q-TAT was
      found to be more sensitive than widely used slot-blot methods but somewhat less
      sensitive than real-time PCR. Among samples containing DNA concentrations ranging
      from 100 pg/microL to 2-4 ng/microL, Q-TAT produced DNA concentration estimates
      that agreed reasonably well with either Quantiblot or real-time PCR. Q-TAT was
      reproducible with a typical coincidence of variation of about 35%. Quantitation
      of human DNA in this study involved summing fluorescence in X and Y amplicons in
      unknowns and quantitation standards. However, analyzing fluorescence in X and Y
      amplicons individually could allow estimates of male and female DNA present in
      mixtures to be made. Moreover, since X and Y amplicons exhibit sizes of 210 and
      216 bp, respectively, the integrity as well as the concentration of the genomic
      DNA template can be assessed. Q-TAT represents an alternate method useful for the
      quantitation of human genomic DNA prior to amplification of STR loci used for
      identity testing purposes. The method uses existing equipment and procedures in
      conjunction with a well-characterized DNA standard to produce concentration
      estimates for unknowns that reliably produce STR profiles suitable for analysis.

PMID- 16423227
TI  - Capillary electrophoretic analysis of phosphorus species in clandestine
      methamphetamine laboratory samples.
AB  - The clandestine manufacture of methamphetamine is a spreading epidemic.
      Manufacturing methods are constantly changing, necessitating the implementation
      of new analytical tools to identify materials from these labs. Characterization
      of phosphate, phosphite, and hypophosphite ions is necessary to distinguish the
      various phosphorus-iodine manufacturing methods that are popular methods for
      reducing pseudoephedrine to methamphetamine. This work describes a capillary
      electrophoresis method to separate acetate, azide, bromide, carbonate, chlorate,
      chloride, chromate, fluoride, hypophosphite, iodide, nitrate, nitrite,
      perchlorate, phosphate, phosphite, sulfate, sulfite, and thiocyanate. The
      CElixerOA 8.2 dynamic coating system was modified by lowering the capillary
      temperature to 15 degrees C and using an acid flush between runs to remove
      adsorbed materials. This allows detection of ions down to between 10 and 30 parts
      per million with percent relative standard deviations of normalized migration
      times under 0.1%. This method is a valuable tool for the characterization of
      phosphate, phosphite, and hypophosphite in routine analysis of clandestine
      methamphetamine manufacturing evidence and has a broader application in other
      areas of forensic analysis.

PMID- 16423228
TI  - Analysis of a soldered wire burnt in a fire.
AB  - Fire investigators frequently encounter electrical wires with melted ends at fire
      scenes, which can provide useful information on the cause and development of the
      fire even when the melted ends result from the fires. A bead on a melted end of a
      wire was found in the area of origin of a massive fire that lasted for nearly a
      whole day, devastating a factory. The bead appeared to be the end of a wire
      soldered to a terminal. X-ray analysis showed that the bead is a tin-copper
      alloy. Although regular tin-lead solder was used in the factory, lead was not
      detected. This contradictory result stood in the way of fire investigation.
      Therefore, an unused wire soldered with tin-lead solder was heated in an electric
      furnace at 500 degrees C for 3 h for further examination. X-ray analysis of this
      wire showed that copper can be alloyed with tin while losing lead in a long-term
      heat in a fire.

PMID- 16423229
TI  - Incestuous paternity detected by STR-typing of chorionic villi isolated from
      archival formalin-fixed paraffin-embedded abortion material using laser
      microdissection.
AB  - Microscopic examination of a blood clot expelled by a physically and mentally
      disabled woman taken to the emergency room because of genital bleeding revealed
      the presence of chorionic villi encircled by decidua, hemorrhage, and necrosis.
      In order to identify the father of the product of conception, sections of
      formalin-fixed, paraffin-embedded abortion material were subjected to laser
      microdissection: DNA extraction from chorionic villi selectively isolated from
      the surrounding tissues allowed successful STR-typing of fetal cells, which was
      otherwise prevented by excess maternal DNA. The large number of homozygous
      genotypes in the fetal profile suggested incestuous paternity. Analysis of
      reference DNA samples from male relatives excluded the woman's father, paternal
      grandfather, and maternal grandfather, whereas the obligate paternal alleles of
      the fetus were constantly present in the genotypes of the woman's brother,
      clearly demonstrating brother-sister incest (probability of paternity >
      99.99999%).

PMID- 16423230
TI  - Fatal falls from a height: two case studies.
AB  - Two case studies are presented involving fatal falls of adult females from a
      height. One involved a launch at low speed from a balcony, and one involved a
      launch at high speed from the top of a cliff. Crime scene evidence obtained on
      the balcony itself provided a strong indication of homicide, but subsequent
      investigation showed that the fall was accidental. No crime scene evidence was
      obtained for the cliff fall since the fall initially appeared to be just another
      suicide from a popular suicide spot. Subsequent investigations indicated homicide
      based on measurements of cliff height, horizontal distance to the impact, and
      available runup distance, plus measurements of possible run, jump, and throw
      speeds. It was found that a female weighing 61 kg (134 lb) can be thrown at
      speeds up to 4.85 m/s by a strong male, more than enough to account for the
      estimated launch speed (4.5 m/s). Given the available 4.0 m runup distance, it
      was found that women of better than average rather than elite athletic ability
      can dive at speeds of about 3.5 m/s or jump feet first at speeds of about 4.0
      m/s, both being less than the estimated launch speed. The decedent had no
      athletic ability and landed head first after falling through a height of 29 m.

PMID- 16423231
TI  - Color separation in forensic image processing.
AB  - In forensic image processing, it is often important to be able to separate a
      feature from an interfering background or foreground, or to demonstrate colors
      within an image to be different from each other. In this study, a color
      deconvolution algorithm that could accomplish this task is described, and it is
      applied to color separation problems in document and fingerprint examination.
      Subtle color differences (sometimes invisible to the naked eye) are found to be
      sufficient, which is demonstrated successfully for several cases where color
      differences were shown to exist, or where colors were removed from the foreground
      or background. The software is available for free in the form of an Adobe
      Photoshop-compatible plug-in.

PMID- 16423232
TI  - Forensic anthropology and the most probable cause of death in cases of violations
      against international humanitarian law: an example from Bosnia and Herzegovina.
AB  - This study presents the results of the analysis of at least 298 predominantly
      male individuals, between 15 and 75 years, who were recovered from an open cast
      mine in Bosnia-Herzegovina. Particular attention is paid to identifying the
      mechanisms of injury and determination of the most probable cause of death based
      on the assessment of lethal or lethal-if-untreated injuries recorded in the
      skeleton. It was calculated that at least 38.9% (155/398) of individuals
      sustained gunshot wounds (GSWs) (plus one shrapnel wound) and may have died as
      consequence of these injuries. Among individuals who died from GSWs, there were
      142 males (91.60%), eight females (5.1%) and five cases that were (3.2%)
      undetermined. One male individual sustained shrapnel injuries. This study
      presents an example of the multidisciplinary approach to the effective forensic
      investigation of violation against International Humanitarian Law, as well as an
      example of how it is possible to obtain meaningful results to assist the needs of
      the prosecution in these kind of cases despite the large number of cases and
      technological constraints.

PMID- 16423233
TI  - Lessons learned from large-scale comparative dental analysis following the South
      Asian tsunami of 2004.
AB  - The aim of this study was to examine the quality of the ante-(AM) and postmortem
      (PM) dental data that were submitted for entry into the PLASS data system in
      Phuket, Thailand, following the Boxing Day (December 26) Tsunami, 2004. The
      investigators were two forensic odontologists who were part of the New Zealand
      Disaster Victim Identification team that worked at Wat Yang Yao morgue and at the
      Information Management Center in Phuket. Our findings underline the usefulness of
      dental data in human identification, but point to a number of significant sources
      of error. Of the 78 PM records received, only 68% of radiographs and 49% of
      photos confirmed the accompanying dental charting. This underlines the value,
      particularly of photographs of the dental arches, in quality control. It also
      points to a large error component, which may have been due to inexperience of the
      operators, fatigue, poor conditions in the temporary morgue, or the problem of
      tooth-colored fillings. Of the 106 AM records received, 62% were of unacceptable
      quality and 64% were either not accompanied by radiographs or had poor quality
      radiographs. These results indicate that AM data collection ideally needs to be
      collated and checked by a forensically trained dentist(s) in the country of
      origin.

PMID- 16423234
TI  - Dental CT imaging as a screening tool for dental profiling: advantages and
      limitations.
AB  - The use of dental processing software for computed tomography (CT) data
      (Dentascan) is described on postmortem (pm) CT data for the purpose of pm
      identification. The software allows reconstructing reformatted images comparable
      to conventional panoramic dental radiographs by defining a curved reconstruction
      line along the teeth on oblique images. Three corpses that have been scanned
      within the virtopsy project were used to test the software for the purpose of
      dental identification. In every case, dental panoramic images could be
      reconstructed and compared to antemortem radiographs. The images showed the basic
      component of teeth (enamel, dentin, and pulp), the anatomic structure of the
      alveolar bone, missing or unerupted teeth as well as restorations of the teeth
      that could be used for identification. When streak artifacts due to metal
      containing dental work reduced image quality, it was still necessary to perform
      pm conventional radiographs for comparison of the detailed shape of the
      restoration. Dental identification or a dental profiling seems to become possible
      in a noninvasive manner using the Dentascan software.

PMID- 16423235
TI  - Immunohistochemical expression of HIF-1alpha in response to early myocardial
      ischemia.
AB  - This study aims to evaluate the effects of ischemia on the myocardial fibers and
      the expression of the transcriptional factor for angiogenesis hypoxia-inducible
      factor-1 alpha (HIF-1alpha) in human heart specimens. We have prospectively
      analyzed the HIF-1alpha expression in human ischemic hearts with the ABC
      inmunohistochemistry technique and amplification by biotinylated tyramide. The
      relationship between the expression of HIF-1alpha and the temporal evolution of
      ischemia has also been evaluated. As pathomorphological diagnosis of early
      myocardial ischemia has many problems in human autopsy material with less than 4
      to 6 h after clinical onset, we suggest that HIF-1alpha is helpful in the early
      acute myocardial infarction diagnosis, so it stains necrotic areas within the
      first 2 h. The amplification procedure provides a higher intensity of the final
      staining without losing specificity. It is concluded that in normal cardiac
      fibers, basal expression of HIF-1alpha is not appreciable, but it steadily
      increases after ischemia. With regard to the practical applicability in forensic
      field, our observations suggest that positive immunohistochemical expression of
      HIF-1alpha on heart samples may be used as a reliable indicator of myocardial
      damage in cases without cardiac lesion evidence, using conventional microscopy.
      This method is especially useful and may provide definitive proof of myocardial
      ischemia in unexpected deaths without previous symptoms, or in forensic cases
      with a short period of clinical manifestations. In addition, it may have been
      involved in possible future cardiovascular therapies.

PMID- 16423236
TI  - Investigation of nocturnal oviposition by necrophilous flies in central Texas.
AB  - The need to accurately estimate the postmortem interval (PMI) has prompted
      research into factors affecting fly oviposition (i.e., oviposition and/or
      larviposition) on a corpse. Research efforts have focused on whether or not
      diurnally active flies oviposit during nighttime hours. This study reports that
      nocturnal oviposition (defined as occurring between 2100-0600 h CDST (Central
      Daylight Savings Time)) did not occur on freshly killed white rats or mice, on
      beef (fresh or aged up to 48 h), on freshly thawed pigs, nor, usually, on thawed
      pigs that were aged for up to 48 h. Limited oviposition did occur between 2100
      and 2120 h on one bloated pig at a lighted rural site. Necrophilous flies were
      present and active at lighted and dark sites (urban and rural) before and
      immediately after sunset, but fly activity on the bait ceased within 50 min
      postsunset and did not resume until after 0600 h. These observations support
      other studies reporting that diurnally active flies do not oviposit during the
      nighttime.

PMID- 16423238
TI  - A distant-range, suicidal shotgun wound of the back.
AB  - The case being reported is one of a shotgun fatality with a thoracic back wound.
      A 23-year-old man was shot from a distance with trajectories going from back to
      front and on a nearly horizontal level. These findings observed in the autopsy
      could represent homicide, but scene investigation and police records were
      interpreted and it became clear that the case was suicide. Thus, this case shows
      that the determination of the manner of death requires a careful forensic
      investigation including autopsy findings, scene investigation, and reconstruction
      of the events.

PMID- 16423237
TI  - Resuscitation injuries complicating the interpretation of premortem trauma and
      natural disease in children.
AB  - Minor soft tissues injuries are common in both adults and children who have had
      cardiopulmonary resuscitation (CPR). Potentially life-threatening injuries are
      rare. The pre-arrest history in a resuscitated adult often assists the
      pathologist to interpret autopsy findings. In contrast, an infant or child may
      not have a reliable history. In this situation, it may be difficult if not
      impossible to distinguish resuscitation injuries from pre-existing accidental or
      inflicted trauma. I describe two children who had significant autopsy-documented
      injuries initially attributed to abuse. The State filed murder charges against
      the caretaker in each case. However, further history and review of the medical
      records suggested that resuscitation rather than pre-arrest trauma caused almost
      all of the injuries. The State dismissed the charges in the first case. A jury
      returned a "not guilty" verdict in the second. It is essential to consider the
      entire history and not just autopsy findings when performing a death
      investigation.

PMID- 16423239
TI  - Pulmonary interstitial emphysema in live birth determination: radiographic and
      gross pathologic features.
AB  - Pulmonary interstitial emphysema (PIE) has previously been reported as a useful
      finding in the determination of live birth in cases where the birth and death
      were not attended. Herein, we present the radiographic and gross pathologic
      features of PIE in such a case. In this instance, in addition to parenchymal
      interstitial emphysema, there were subpleural air collections and a pneumothorax.

PMID- 16423240
TI  - Aqua-eroticum: an unusual autoerotic fatality in a lake involving a home-made
      diving apparatus.
AB  - The term Aqua-eroticum was first introduced in 1984 by Sivaloganathan to describe
      the unusual autoerotic death of a man using submersion as an asphyxia method.
      This was the first case of that kind, and since then, no other case of autoerotic
      submersion has been reported, nor other autoerotic fatality in open water. Here
      we report the case of a 25-year-old man, nude under a home-made plastic body
      suit, overdressed for the season with winter clothes and restrained by complex
      bondage. He was submersed, tied underwater to a boat and was using a home-made
      diving apparatus for air supply. Death was ruled as accidental autoerotic
      asphyxia from rebreathing, caused by the faulty air-supply device.

PMID- 16423241
TI  - Autoerotic deaths in the literature from 1954 to 2004: a review.
AB  - Autoerotic death by hanging or ligature is a method of autoeroticism well known
      by forensic pathologists. In order to analyze autoerotic deaths of nonclassic
      hanging or ligature type, this paper reviews all published cases of autoerotic
      deaths from 1954 to 2004, with the exclusion of homicide cases or cases in which
      the autoerotic activity was not solitary. These articles were obtained through a
      systematic Medline database search. A total of 408 cases of such deaths has been
      reported in 57 articles. For each case, the following characteristics are
      presented here: sex, age, race, method of autoerotic activity, cause of death,
      and location where the body was found. Autoerotic death practioners were
      predominantly Caucasian males. Victims were aged from 9 to 77 years and were
      mainly found in various indoor locations. Most cases were asphyxia by hanging,
      ligature, plastic bags, chemical substances, or a mixture of these. Still,
      atypical methods of autoerotic activity leading to death accounted for about
      10.3% of cases in the literature and are classified here into five broad
      categories: electrocution (3.7%), overdressing/body wrapping (1.5%), foreign body
      insertion (1.2%), atypical asphyxia method (2.9%), and miscellaneous (1.0%). All
      these atypical methods are further discussed individually.

PMID- 16423242
TI  - The RECON typology of stalking: reliability and validity based upon a large
      sample of North American stalkers.
AB  - A new typology of stalking, RECON (relationship and context-based), is proposed,
      based upon the prior relationship between the pursuer and the victim, and the
      context in which the stalking occurs. The static typology yields four groups:
      Intimate, Acquaintance, Public Figure, and Private Stranger. The typology was
      tested on a large (N = 1005) nonrandom sample of North American stalkers gathered
      from prosecutorial agencies, a large police department, an entertainment
      corporation security department, and the authors' files. Interrater reliability
      for group assignment was 0.95 (ICC). Discriminant validity (p < 0.01) was
      demonstrated on a variety of demographic, clinical, pursuit, threat, and violence
      characteristics among and between groups. Findings confirm and extend the work of
      other researchers, most notably the very high risk of threats and violence among
      prior sexually intimate stalkers, the very low risk of threats and violence among
      public figure (celebrity) stalkers, and the negative relationship between
      stalking violence and psychosis.

PMID- 16423243
TI  - Risk of harm: inmates who harm themselves while in prison psychiatric treatment.
AB  - In this study, 242 randomly selected male offenders who were receiving
      psychiatric treatment in prison were administered psychological and
      neuropsychological evaluations and were followed during their treatment in a
      prison psychiatric hospital. Offenders who harmed themselves in treatment were
      compared to those who did not harm themselves. Eighteen percent of offenders
      harmed themselves, the severity of which required medical intervention. Young
      age, drug abuse, absence of Axis I mental disorder but presence of Axis II
      borderline personality disorder identified offenders who harmed themselves.
      Psychopathy checklist-revised (PCL-R) total rating > or = 30 and PCL-R Factor 2
      (antisocial lifestyle) rating also identified offenders who harmed themselves.
      Additionally, offenders who harmed themselves also were 8.36 times more likely
      than their cohorts to harm treatment staff. Theoretical understanding of
      offenders who harm themselves, the importance of considering the environmental
      context in identifying risk factors for self-harm, and implications for treatment
      are suggested.

PMID- 16423244
TI  - Juvenile sex offenders: a complex population.
AB  - Individuals who engage in sexual offending behavior represent a heterogeneous
      population. Recent research has found some success in categorizing sexual
      offenders based on a number of variables, particularly the type of victim. For
      example, differences have been found between those offenders who victimize adults
      when compared with those who victimize children. However, the research in this
      area has been conducted predominantly with adult samples. As the adult sex
      offender literature has progressed, it has become evident that risk assessment,
      treatment effectiveness, and risk management are dependent on such offender
      characteristics. Unfortunately, the relevance to juveniles of characteristics
      deemed to be important with adult sex offenders is limited due to the complexity
      of developmental processes, particularly with respect to mental disorders and
      personality formation. As such, the formulation and implementation of treatment
      and risk management strategies that will be effective with juvenile sex offenders
      are challenging. The goal of this paper is to review some of the complexities
      inherent in the juvenile sex offender population by focusing on specific areas of
      complication, including: classification systems, comorbid paraphilias and other
      mental illnesses, and maladaptive personality traits.

PMID- 16423245
TI  - Results of a proposed breath alcohol proficiency test program.
AB  - Although proficiency test programs have long been used in both clinical and
      forensic laboratories, they have not found uniform application in forensic breath
      alcohol programs. An initial effort to develop a proficiency test program
      appropriate to forensic breath alcohol analysis is described herein. A total of
      11 jurisdictions participated in which 27 modern instruments were evaluated. Five
      wet bath simulator solutions with ethanol vapor concentrations ranging from
      0.0254 to 0.2659 g/210 L were sent to participating programs, instructing them to
      perform n = 10 measurements on each solution using the same instrument. Four of
      the solutions contained ethanol only and one contained ethanol mixed with
      acetone. The systematic errors for all instruments ranged from -11.3% to +11.4%
      while the coefficient of variations ranged from zero to 6.1%. A components-of
      variance analysis revealed at least 79% of the total variance as being due to the
      between-instrument component for all concentrations. Improving proficiency test
      program development should consider: (1) clear protocol instructions, (2)
      frequency of proficiency testing, (3) use lower concentrations for determining
      limits-of-detection and -quantitation, etc. Despite the lack of a biological
      component, proficiency test participation should enhance the credibility of
      forensic breath test programs.

PMID- 16423246
TI  - A large-scale study of the relationship between blood and breath alcohol
      concentrations in New Zealand drinking drivers.
AB  - Blood alcohol concentrations (BAC) and corresponding breath alcohol
      concentrations (BrAC) were determined for 21,582 drivers apprehended by New
      Zealand police. BAC was measured using headspace gas chromatography, and BrAC was
      determined with Intoxilyzer 5000 or Seres Ethylometre infrared analysers. The
      delay (DEL) between breath testing and blood sampling ranged from 0.03 to 5.4 h.
      BAC/BrAC ratios were calculated before and after BAC values were corrected for
      DEL using 19 mg/dL/h as an estimate of the blood alcohol clearance rate.
      Calculations were performed for single and duplicate breath samples obtained
      using the Intoxilyzer (groups I-1 and I-2) and Seres devices (groups S-1 and S
      2). Before correction for DEL, BAC/BrAC ratios for groups I-1, I-2, S-1, and S-2
      were (mean+/-SD) 2320+/-260, 2180+/-242, 2330+/-276, and 2250+/-259,
      respectively. After BAC values were adjusted for DEL, BAC/BrAC ratios for these
      groups were (mean+/-SD) 2510+/-256, 2370+/-240, 2520+/-280, and 2440+/-260,
      respectively. Our results indicate that in New Zealand the mean BAC/BrAC ratio is
      19-26% higher than the ratio of the respective legal limits (2000).

PMID- 16423248
TI  - Genetic polymorphism at 15 tetrameric short tandem repeat loci in four aboriginal
      tribal populations of Bengal.
AB  - POPULATIONS: This study reports the genetic polymorphism observed at 15 short
      tandem repeat loci D3S1358, TH01, D21S11, D18S51, D5S818, D13S317, D7S820,
      D16S539, CSF1PO, vWA, D8S1179, TPOX, D2S1338, D19S433, and FGA in four aboriginal
      populations of Bengal. The analysis was performed to decipher the suitability of
      CODIS as well as six other highly polymorphic and unlinked markers in Forensic
      Testing. Studied populations include four tribes: Karmali, Kora, Maheli, and
      Lodha.

PMID- 16423247
TI  - Postmortem tissue distribution of atomoxetine following fatal and nonfatal doses-
      three case reports.
AB  - Atomoxetine (Strattera, Lilly) is a selective norepinephrine reuptake inhibitor
      (SNRI) prescribed for the treatment of attention-deficit/hyperactivity disorder
      (ADHD) in children, adolescents, and adults. It is the first nonstimulant drug
      therapy option for ADHD. Three case reports are presented in which atomoxetine
      was detected in two individuals who died from causes unrelated to the drug and a
      third from the intentional ingestion of atomoxetine and other drugs. In addition,
      a brief description of the pharmacokinetics and side effects of atomoxetine are
      given. Postmortem fluid and tissue concentrations of atomoxetine were as follows:
      aortic blood, <0.1-8.3 mg/L; femoral blood, 0.33-5.4 mg/L; vitreous humor, 0.1
      0.96 mg/L; bile, 1.0-33 g/L; urine, <0.1 mg/L; liver, <0.44-29 mg/kg; and gastric
      contents, 0.0097-16.8 mg total. Autopsy findings in the two cases in which death
      was not attributed to drug toxicity included arrhythmogenic right ventricular
      dysplasia and hypertrophic cardiomyopathy. The analytical method utilized was a
      modified basic drug, liquid-liquid procedure followed by gas chromatography/mass
      spectrometry and nitrogen phosphorous detection. Atomoxetine can be considered
      nontoxic at whole blood and liver concentrations below 1.3 mg/L and 5 mg/kg,
      respectively.

PMID- 16423249
TI  - Genetic polymorphisms of 15 STR loci in a Japanese population.

PMID- 16423250
TI  - Genetic profile of nine autosomal STR loci among Halakki and Kunabhi populations
      of Karnataka, India.
AB  - POPULATION: Blood samples were collected from a total of 84 healthy and unrelated
      Halakki (44) and Kunabhi (40) populations, with their informed written consent.
      The geographic location of the sampled area is shown in Fig. 1. Both the
      populations are endogamous, and they belong to Dravidian linguistic family.
      Halakki is a tribal group having a population size of approximately 3383. They
      claim that they originally belong to Gujarat and Rajasthan, and migrated through
      Andhra Pradesh to Karnataka. Kunabhi is also a tribal population, who are
      approximately 35,214 in number. The male Kunabhi can be identified by their
      tattoo marks. A necklace is the symbol of married women. They were hunters and
      gatherers, but at present they practice agriculture.

PMID- 16423251
TI  - Allele frequency distributions at three pentanucleotide repeat STRs in a Japanese
      population.

PMID- 16423252
TI  - Analysis of Y-STR loci in a population sample from northeast China.

PMID- 16423253
TI  - DNA sequence characterization of the FGA STR locus in the free state population
      of South Africa.

PMID- 16423260
TI  - New Aspects in Pulmonary Surfactant Biology and Disease. Proceedings of the 3rd
      Conference in the Japanese Surfactant Molecular Pathophysiology Meetings Series,
      12-13 November 2004, Osaka, Japan.

PMID- 16423262
TI  - Biology of alveolar type II cells.
AB  - The purpose of this review is to highlight the many metabolic properties of
      alveolar type II cells, their production of surfactant, their role in innate
      immunity, and their importance in the repair process after lung injury. The
      review is based on the medical literature and results from our laboratory. Type
      II cells produce and secrete pulmonary surfactant and for that purpose they need
      to synthesize the lipids of surfactant. One of the regulators of lipogenesis is
      the transcription factor sterol regulatory element binding protein-1c (SREBP-1c).
      This is a key transcription factor regulating fatty acid synthesis. Type II cells
      also proliferate to restore the epithelium after lung injury, clear alveolar
      fluid by transporting sodium from the apical to the basolateral surface, and
      participate in the innate immune response to inhaled materials and organisms. The
      type II cell is, in many ways, the defender of the alveolus. However, the type II
      cells work in concert with the other cells in the gas exchange regions of the
      lung to keep the alveoli open and reduce inflammation due to irritants in the air
      we breathe.

PMID- 16423263
TI  - Extra-pulmonary aspects of acquired pulmonary alveolar proteinosis as predicted
      by granulocyte-macrophage colony-stimulating factor-deficient mice.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF)-/- mice are an
      invaluable model for exploring the effects of systemic GM-CSF deficiency. Their
      lung phenotype exactly reproduces the abnormalities seen in human pulmonary
      alveolar proteinosis (PAP). However, GM-CSF-/- mice also have significant
      systemic functional abnormalities. These include immune defects which result in a
      reduced susceptibility to a range of experimentally induced autoimmune disorders.
      These immunological defects are also functionally manifest as an impaired ability
      to resolve a range of infections under certain conditions, usually implicating
      cellular effectors, including Listeria, Group B streptococcus, adenovirus,
      Pneumocystis carinii, and malaria. These observations are consistent with the
      known propensity for patients with PAP to develop a range of opportunistic
      infections. Conversely, the diminished immunological response to inflammatory
      stimuli may be beneficial in some settings by limiting inflammatory cell
      recruitment and pro-inflammatory mediator-release. GM-CSF-/- mice also have
      distinct fertility defects, manifest as reduced litter size and an increased rate
      of early fetal loss. These observations may be clinically relevant for women
      affected by PAP and further support the evaluation of the role of GM-CSF in human
      reproduction. These observations reinforce the importance of clinicians viewing
      PAP as a state of systemic functional GM-CSF deficiency, albeit with prominent
      pulmonary manifestations, rather than purely a 'lung disease'. These systemic
      manifestations of GM-CSF deficiency should also be considered when deciding on
      the choice between pulmonary or systemic delivery of GM-CSF as therapy for PAP,
      as only systemic drug delivery has the potential capacity to correct the systemic
      manifestations of GM-CSF deficiency in these patients.

PMID- 16423264
TI  - Pulmonary surfactant proteins and lipids as modulators of inflammation and innate
      immunity.
AB  - OBJECTIVES: The pulmonary surfactant system of the human lung consists of unique
      lipids and proteins that contribute to the biophysical and innate immune
      properties of the organ. Surfactant protein A (SP-A) is an oligomeric protein
      consisting of 18 protomers with collagen and lectin-like domains that recognizes
      glycoconjugates, lipids and protein determinants on both host cells and invading
      microorganisms. The authors examined the interaction of SP-A with Mycoplasma
      pneumoniae and the influence of the protein upon the innate immune response to
      the bacteria. METHODOLOGY: The authors quantified SP-A interaction with bacteria
      using ELISA, and identified the major surface ligand by thin layer
      chromatography, HPLC and mass spectrometry. The inflammatory response of human
      and rat macrophages was measured by quantifying tumour necrosis factor-alpha
      secretion using ELISA, and nitric oxide production. RESULTS: SP-A bound the
      bacteria with high affinity and enhanced the inflammatory response of human and
      rat macrophages to the organism and its membranes. Analysis of the interaction of
      SP-A with the bacteria revealed that the major ligand was a phospholipid. The
      lipid ligand was purified by a combination of thin layer and HPLC, and identified
      by mass spectrometry. The mass spectrometry demonstrated that the SP-A reactive
      lipid consisted of several disaturated molecular species of phosphatidylglycerol
      (PtdGro). Additional experiments were performed to determine if disaturated
      PtdGro was capable of interfering with the action of SP-A as an inhibitor of
      bacterial lipopolysaccharide-induced inflammatory mediator production by
      macrophages. The disaturated PtdGro failed to alter the anti-inflammatory action
      of SP-A but unexpectedly these same studies revealed that unsaturated PtdGro can
      modify the host response to lipopolysaccharide. CONCLUSIONS: These findings
      reveal that both the lipids and proteins of pulmonary surfactant play a role in
      regulating the host response to invading microorganisms.

PMID- 16423266
TI  - Surfactant catabolism.
AB  - Alveolar pulmonary surfactant is a complex of macromolecular aggregates composed
      of phospholipids and surfactant proteins (SP) that is essential for maintenance
      of normal lung function. The importance of surfactant homeostasis is recognized
      in the patients and the animal models with pulmonary disease, although the
      mechanisms of surfactant homeostasis are not fully understood. In this review the
      author will discuss: (i) the mechanisms of the surfactant catabolism by
      macrophage and type II cells; and (ii) the important role of SP-D on
      ultrastructure of surfactant that affects uptake by type II cells.

PMID- 16423267
TI  - Alveolar epithelial cells: differentiation and lung injury.
AB  - Re-epithelialization of alveolar epithelial cells is one of the important repair
      processes in many types of lung injury. The major functions of alveolar type II
      cells are synthesis and secretion of surfactant, hyperplasia in reaction to
      alveolar epithelial injury, and serving as progenitor cells for alveolar type I
      cells. The authors have examined the effects of several soluble factors on
      cultured alveolar type II cells in vitro, and also examined the histopathology
      and gene expression of surfactant proteins in the rat lungs with LPS, bleomycin
      and/or treated with keratinocyte growth factor. The authors next examined the
      effects of bone marrow stromal cells (BMSC) implanted transvenously into
      bleomycin-induced lungs. The authors found that keratinocyte growth factor (KGF)
      is a strong growth factor for alveolar type II cells, and that KGF instillation
      prevents bleomycin-induced lung injury. Furthermore, the authors showed the
      possibility of differentiation of implanted BMSC into alveolar epithelial cells.
      KGF and BMSC may play an important role in maintaining the alveolar epithelium
      and repairing the damaged epithelium after injury, and may well provide potential
      therapeutic alternatives.

PMID- 16423268
TI  - Functional heterogeneity of colony-stimulating factor-induced human monocyte
      derived macrophages.
AB  - OBJECTIVES: Macrophages (Mphis) have various functions and play a critical role
      in host defense and the maintenance of homeostasis. Mphis exist in every tissue
      in the body, but Mphis from different tissues exhibit a wide range of phenotypes
      with regard to their morphology, cell surface antigen expression and function,
      and are called by different names. However, the precise mechanism of the
      generation of macrophage heterogeneity is not known. In the present study, the
      authors examined the functional heterogeneity of Mphis generated from human
      monocytes under the influence of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and macrophage-CSF (M-CSF). METHODOLOGY: CD14 positive human monocytes
      (Mos) were incubated with M-CSF and GM-CSF for 6-7 days to stimulate the
      generation of M-CSF-induced monocyte-derived Mphis (M-Mphis) and GM-CSF-induced
      monocyte-derived Mphis (GM-Mphis), respectively. The expression of cell surface
      antigens and several functions such as antigen presenting cell activity,
      susceptibility to oxidant stress, and the susceptibility to HIV-1 and
      mycobacterium tuberculosis infection were examined. RESULTS: GM-Mphis and M-Mphis
      are distinct in their morphology, cell surface antigen expression, and functions
      examined. The phenotype of GM-Mphis closely resembles that of human Alveolar
      Mphis (A-Mphis), indicating that CSF-induced human monocyte-derived Mphis are
      useful to clarify the molecular mechanism of heterogeneity of human Mphis, and GM
      Mphis will become a model of human A-Mphis.

PMID- 16423269
TI  - Alveolar macrophages and emphysema in surfactant protein-D-deficient mice.
AB  - Surfactant protein-D (SP-D) is a member of the collectin family of collagenous
      proteins with lectin activity. SP-D is expressed in numerous tissues, primarily
      in type II alveolar cells in the periphery of the lung. SP-D plays an important
      role in host defense of the lung. To evaluate the importance of SP-D in vivo,
      transgenic mice lacking SP-D (SP-D-/- mice) have been generated. Lipid
      accumulation and airspace enlargement were observed in the lungs of SP-D-/- mice
      within 3 weeks after birth, and progressed with advancing age. Airspace
      enlargement and abnormalities in elastin fibers supported the concept that SP-D
      was required to inhibit destruction of the alveoli. Alveolar macrophages from SP
      D-/- mice produced more H2O2 and matrix metalloproteinases (MMP)-2, -9, and -12
      compared with wild-type mice. In vitro studies demonstrated that oxidants derived
      in part from NADPH oxidase enhanced NF-kappaB activation and MMP production in
      alveolar macrophages from SP-D-/- mice. A specific inhibitor of NF-kappaB reduced
      MMP production by alveolar macrophages from SP-D-/- mice. Taken together, these
      data demonstrated oxidant-dependent activation of NF-kappaB and enhanced MMP
      expression by alveolar macrophages from SP-D-/- mice, a process likely to mediate
      airspace remodeling caused by SP-D deficiency. SP-D plays a critical role in
      regulating alveolar macrophage activation, oxidant production, and MMP activity
      that may influence the pathogenesis of various pulmonary disorders.

PMID- 16423270
TI  - Clinical features and genetic analysis of surfactant protein C in adult-onset
      familial interstitial pneumonia.
AB  - Familial cases of interstitial pneumonia (FIP) have been reported to be linked to
      mutations of the surfactant protein C (SP-C) gene. Based on this knowledge, we
      evaluated the characteristics of patients with adult-onset FIP in the Tokyo area
      using clinical and radiopathological findings, and further evaluated the genetic
      background of patients with FIP compared with sporadic IP patients using genetic
      sequencing of the SP-C gene. A total of 22 patients with FIP from 13 families
      were identified, and the mean age at first diagnosis of these patients was 50 +/-
      2.7 years (range: 20-66 years). Based on the specimen histology, UIP and non
      specific interstitial pneumonia accounted for 64 and 36%, respectively.
      Distribution of the interstitial pattern in HRCT imaging resulted in 36% upper
      lung dominant, 5% whole lung and 59% lower lung dominant. Two missense mutations
      in exon 4 (N138T) and exon 5 (N186S) were identified in the SP-C gene from 11
      cases with FIP. Each exonic mutation consisted of DNA polymorphism. The
      frequencies of these DNA polymorphisms were evaluated among 11 subjects with FIP,
      30 subjects with sporadic IP, and 43 healthy volunteers as controls.
      Interestingly, the genotype and allele frequencies in exon 5 were statistically
      different among these groups. In particular, the N186S substitution of exon 5 in
      the SP-C gene was shown in patients with FIP or sporadic IP, with a statistically
      higher frequency. While pathophysiological mechanisms remain to be elucidated,
      the N186S missense variant may have potential susceptibility in the development
      of IP. The gene or genes that prove to be important in the development of FIP may
      provide insights into the pathogenesis of other forms of interstitial lung
      diseases.

PMID- 16423271
TI  - Regulation of inflammation and bacterial clearance by lung collectins.
AB  - Pulmonary surfactant proteins (SP) A and D play important roles in the innate
      immune system of the lung. These proteins belong to the collectin subgroup in
      which lectin domains are associated with collagenous structures. To obtain a
      better understanding of how lung collectins modulate cellular responses, the
      authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2).
      SP-A bound to TLR2 and inhibited interactions between TLR2 and TLR2-ligands such
      as peptidoglycan (PGN) and zymosan. NF-kappaB activation and tumour necrosis
      factor-alpha expression induced by PGN or zymosan were significantly inhibited in
      the presence of SP-A. Lung collectins may act as inhibitors of lung inflammation
      in respiratory infections. The authors also examined the effects of lung
      collectins on the phagocytosis of bacteria by alveolar macrophages. Lung
      collectins enhanced the uptake of S. pneumoniae or M. avium by alveolar
      macrophages. It was demonstrated that the direct interaction of lung collectins
      with macrophages resulted in increased cell surface expression of scavenger
      receptor A or mannose receptor, which are responsible for phagocytosis. This
      study has emphasized the biological relevance of SP-A and SP-D against various
      respiratory infections, however, a more complete understanding of the molecular
      mechanism is required.

PMID- 16423272
TI  - Monitoring markers of disease activity for interstitial lung diseases with serum
      surfactant proteins A and D.
AB  - OBJECTIVES: Surfactant protein (SP) A and D are specific serum markers for
      interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). The
      authors evaluated the critical roles of these markers on the prognoses of
      patients with IPF and the mechanisms of their elevation in sera. METHODOLOGY: The
      authors evaluated the relationship between prognosis and the serum markers in 82
      IPF patients. The protein content and mRNA expression of the markers were
      evaluated using rats with interstitial pneumonia induced by bleomycin
      administration. RESULTS: Higher levels of serum SP-D at the time of the initial
      visit to the Sapporo Medical University Hospital were associated with poorer
      prognoses, while SP-A showed no significant affect on survival. Causes of the
      elevation in sera were due to the acceleration of, not only production in the
      lungs, leakage into the circulation. The elevation was associated with alveolitis
      but not fibrosis. CONCLUSIONS: SP-D is a good predictor of the prognosis in
      patients with IPF.

PMID- 16423273
TI  - Epidemiological and clinical features of idiopathic pulmonary alveolar
      proteinosis in Japan.
AB  - Idiopathic pulmonary alveolar proteinosis (IPAP) is a rare disease characterized
      by excessive amounts of lipoproteinaceous material in the alveolus. This report
      presents an interim analysis of nationwide epidemiological data from Japanese
      patients with pulmonary alveolar proteinosis, and the roles of serum markers for
      IPAP. (i) The nationwide demographic data from 166 Japanese patients with IPAP
      are shown. The female to male ratio was 1:2, and the average age was 51 +/- 14
      years old (age range: 15-79 years) at registration or diagnosis. A total of 30%
      of patients with IPAP have a poor clinical course. In total, 30% of patients were
      treated with whole lung lavage therapy (WLL). Under WLL, the patients
      significantly improved in the short term, but 40% of the patients who underwent
      WLL worsened again. A new strategy such as granulocyte-macrophage colony
      stimulating factor (GM-CSF) therapy for intractable PAP is required. (ii) The
      correlation of serum KL-6, carcinoembryonic antigen, surfactant proteins D and A,
      and LDH with disease severity suggests their potential as disease markers. In
      contrast, serum anti-GM-CSF antibody did not correlate with disease severity, but
      is a specific marker for the diagnosis of IPAP. The combined measurements of the
      serum markers may well prove very useful for both the diagnosis and the
      management of IPAP patients.

PMID- 16423274
TI  - Granulocyte-macrophage colony-stimulating factor inhalation therapy for patients
      with idiopathic pulmonary alveolar proteinosis: a pilot study; and long-term
      treatment with aerosolized granulocyte-macrophage colony-stimulating factor: a
      case report.
AB  - Idiopathic pulmonary alveolar proteinosis (IPAP) is considered to be caused by an
      autoantibody to the granulocyte-macrophage colony-stimulating factor (GM-CSF),
      which neutralizes GM-CSF and therefore impairs the differentiation of alveolar
      macrophages. The authors have previously characterized the BAL fluid and alveolar
      macrophages obtained from three IPAP patients who were successfully treated with
      aerosolized GM-CSF and demonstrated restoration of the cell number, expression of
      surface marker, and phagocytic ability of the alveolar macrophages as well as a
      decrease in the autoantibody levels in the BAL fluid. The condition recurred in
      one of the patients after 20 months. This patient underwent a second and third
      course of GM-CSF inhalation therapy with the same dose and schedule as the first
      one. Since the second therapeutic intervention did not succeed in producing any
      improvement in the symptoms and disease markers, the authors used a new nebulizer
      and a liquid preparation of the drug instead of the lyophilized preparation for
      the third therapeutic session and this restored the respiratory function
      considerably. A 6-month maintenance therapeutic regimen with a lower GM-CSF
      inhalation frequency brought about a further improvement in the disease markers.
      The results suggest that the efficacy of GM-CSF inhalation therapy might be
      related to the drug preparation mode, choice of nebulizer, and duration of
      treatment.

PMID- 16423276
TI  - New concepts in collectin-mediated host defense at the air-liquid interface of
      the lung.
AB  - OBJECTIVES: Surfactant proteins A (SP-A) and D are collectins that play key roles
      in innate immune defense of the lung. Recent studies suggest that these proteins
      have a direct effect on the growth and viability of Gram-negative bacteria,
      Mycoplasma pneumoniae and Histoplasma capsulatum. METHODOLOGY: The researchers
      examined membrane permeabilization by BAL fluid of mice that were sufficient or
      deficient in surfactant proteins, of rough and smooth LPS-containing membranes,
      and of genetically altered bacteria. The permeability assay is based on the
      ability of agents to promote access of impermeable dyes propidium iodide and
      ELF97 to intracellular targets. RESULTS: The permeabilizing activity of
      concentrated BAL material from SP-A+/+ mice was substantially greater than that
      from SP-A-/- animals, and was sensitive to hyperoxic exposure. Oxidation of the
      collectins in vitro also blocked their antimicrobial effects. Rough but not
      smooth LPS conferred susceptibility of model bacterial membranes to
      permeabilization by the collectins. The screening of genetically engineered SP-A
      mice with a Pseudomonas aeruginosa signature tagged mutagenesis library has
      revealed several pathways which are required for resistance to the permeabilizing
      effects of SP-A, including those required for salicylate biosynthesis and
      flagellar function. CONCLUSION: The researchers conclude that the pulmonary
      collectins directly permeabilize bacteria in an LPS-dependent and rough LPS
      specific manner. Oxidative damage blocks the permeabilizing activity of alveolar
      lining fluid and purified proteins. The mechanism(s) of permeabilization is not
      known, but the crystal structure of SP-A reveals a hydrophobic cleft lined by
      charged residues which may play a role in membrane perturbation.

PMID- 16423275
TI  - Why does the autoantibody against granulocyte-macrophage colony-stimulating
      factor cause lesions only in the lung?
AB  - OBJECTIVES: During the course of investigating the etiology of idiopathic
      pulmonary alveolar proteinosis (IPAP), the authors found that the autoantibody
      against granulocyte-macrophage colony-stimulating factor (GM-CSF) was
      consistently present in both sera and the lung tissue. The autoantibody
      completely blocked bioactivity by direct binding with high specificity and
      avidity. Because of the existence of patients with congenital PAP who lack GM-CSF
      receptors and the development of PAP in GM-CSF and GM-CSF receptor knock-out
      mice, the autoantibody is likely to be the causative agent for IPAP. However,
      this finding posed the question as to why the autoantibody against GM-CSF caused
      lesions only in the lung. METHODOLOGY: To answer this question, the authors
      investigated, using immunohistochemistry, confocal laser microscopy, and
      immunoblotting, the expression of PU.1 in tissue macrophages. PU.1 is a critical
      transcription factor for terminal differentiation of alveolar macrophage (AM), as
      reported previously in the lung, liver, spleen, kidney, intestine and brain.
      RESULTS: PU.1 was consistently expressed in the nuclei of normal AM, but faintly
      or not at all in IPAP-AM. Moreover, it was not expressed in the nuclei of any
      other normal tissue macrophages tested. Blood monocytes expressed PU.1 in the
      cytosol but not in the nuclei. These results suggested that the differentiation
      pathway is different between AM and other tissue macrophages. PU.1 was not
      expressed in the nuclei of newborn rat lung AM but was gradually expressed during
      the first 10 days. CONCLUSIONS: The authors demonstrated that GM-CSF is crucial
      for terminal differentiation of AM, but not for that of other tissue macrophages.

PMID- 16423277
TI  - Pulmonary surfactant transport in alveolar type II cells.
AB  - Pulmonary surfactant (PS) is a mixture of several lipids (mainly
      phosphatidylcholine; PC) and four apoproteins (A, B, C and D). The classical
      hypothesis of PS transport suggests that PS is synthesized in the endoplasmic
      reticulum and transported to the lamellar body (LB) via the Golgi apparatus.
      However, recent studies have raised questions regarding this single route. This
      study examined, independently, the intracellular trafficking route of three
      different components of PS, that is, PC, SP-A and SP-B. Alveolar type II cells
      were isolated from Sprague-Dawley rats or Japanese white rabbits. The cells were
      cultured with either [3H]choline or [35S]methionine/cysteine with or without
      brefeldin A, which disassembles the Golgi apparatus. LB was purified from
      disintegrated cells with sucrose density gradient centrifugation. [3H]PC was
      extracted from radiolabeled media, cells, and the LB fraction with Bligh-Dyer's
      method. [35S]SP-A or [35S]SP-B was immunoprecipitated from each sample with a
      specific antibody. [3H]PC was transported and stored to the LB via a Golgi
      independent pathway. [35S]SP-A was transported to the Golgi apparatus, underwent
      glycosylation, and was then constitutively secreted. The secreted [35S]SP-A was
      re-uptaken into the LB. [35S]SP-B was transported and stored to the LB via the
      Golgi-dependent pathway. These results indicate that, rather than a single route,
      surfactant components take different pathways to reside in the LB. These
      different pathways may reflect the different nature and role of each surfactant
      component such as surface tension-lowering activity and innate host defense.

PMID- 16423278
TI  - Successful treatment of congenital pulmonary alveolar proteinosis with
      intravenous immunoglobulin G administration.
AB  - The authors report a female patient with congenital pulmonary alveolar
      proteinosis (PAP). She had two brothers who died from the same disease. BAL did
      not improve her progressive respiratory failure. After intravenous immunoglobulin
      G (IVIG) administration for complicated hypogammaglobulinemia, she recovered from
      respiratory failure. The efficacy of IVIG was confirmed by recovery from
      deterioration in respiratory status and improvement in chest CT findings on two
      separate occasions. Subsequently, the patient remains free from respiratory
      symptoms for more than 3 years on an ongoing regimen of monthly IVIG. She had no
      surfactant protein (SP) B deficiency. Alveolar macrophages (AM) obtained from her
      BAL fluid were small and showed decreased phagocytotic activity. Immunostaining
      revealed weak expression of PU.1 in her AM, a key protein in AM maturation. All
      nucleotide sequences of granulocyte-macrophage colony stimulating factor (GM
      CSF), GM-CSF-receptor and PU.1 were normal. Endotoxin-induced GM-CSF release from
      peripheral mononuclear cells (PMNC), and proliferation of PMNC in response to GM
      CSF were normal. In addition, an antibody against GM-CSF, as seen in adult
      patients with idiopathic PAP, was not detected in the serum or BAL fluid.
      Although the patient's PMNC secreted only small amounts of IgG and IgM, an EB
      virus-derived cell line of her B cells secreted IgM as much as normal control
      cells. In a flow cytometric study, IgM was expressed on the cell surface. In
      conclusion, an abnormality in a single gene may have decreased secretion of
      immunoglobulin from the B cells and the AM phagocytotic activity in the patient.

PMID- 16423279
TI  - Lipid-soluble smoke particles damage endothelial cells and reduce endothelium
      dependent dilatation in rat and man.
AB  - BACKGROUND: Cigarette smoking is a strong risk factor for vascular disease and
      known to cause dysfunction of the endothelium. However, the molecular mechanisms
      involved are still not fully understood. METHODS: In order to reveal the direct
      effects of lipid-soluble smoke particles on the endothelium, ring segments
      isolated from rat mesenteric arteries and human middle cerebral arteries (MCA)
      obtained at autopsy were incubated for 6 to 48 hrs in the presence of
      dimethylsulphoxide (DMSO)-soluble particles from cigarette smoke (DSP), i.e.
      lipid-soluble smoke particles. The endothelial microstructure was examined by
      transmission electron microscopy. The endothelial function was evaluated by
      acetylcholine (ACh)-induced endothelium-dependent vasodilatation, using a
      sensitive myograph. RESULTS: After DSP treatment, the arterial endothelium was
      swollen and loosing its attachment. In functional tests, the total ACh-induced
      dilatation, the nitric oxide (NO)-mediated and the endothelium-derived
      hyperpolarization factor (EDHF)-mediated dilatations were significantly decreased
      by DSP in a time- and concentration-dependent manner (p < 0.05). Nicotine, an
      important compound in cigarette smoke had, in an equivalent concentration as in
      DSP, no such effects (p > 0.05). Similar results were obtained in the human MCA.
      CONCLUSION: Thus, we demonstrate that the lipid-soluble smoke particles, but not
      nicotine, caused damage to arterial endothelium and reduced the endothelium
      dependent dilatation in man and rat.

PMID- 16423280
TI  - Prevalence of cardiovascular risk factors in a middle-income country and
      estimated cost of a treatment strategy.
AB  - BACKGROUND: We assessed the prevalence of risk factors for cardiovascular disease
      (CVD) in a middle-income country in rapid epidemiological transition and
      estimated direct costs for treating all individuals at increased cardiovascular
      risk, i.e. following the so-called "high risk strategy". METHODS: Survey of risk
      factors using an age- and sex-stratified random sample of the population of
      Seychelles aged 25-64 in 2004. Assessment of CVD risk and treatment modalities
      were in line with international guidelines. Costs are expressed as USD per capita
      per year. RESULTS: 1255 persons took part in the survey (participation rate of
      80.2%). Prevalence of main risk factors was: 39.6% for high blood pressure (> or
      =140/90 mmHg or treatment) of which 59% were under treatment; 24.2% for high
      cholesterol (> or =6.2 mmol/l); 20.8% for low HDL-cholesterol (<1.0 mmol/l); 9.3%
      for diabetes (fasting glucose > or =7.0 mmol/l); 17.5% for smoking; 25.1% for
      obesity (body mass index > or =30 kg/m2) and 22.1% for the metabolic syndrome.
      Overall, 43% had HBP, high cholesterol or diabetes and substantially increased
      CVD risk. The cost for medications needed to treat all high-risk individuals
      amounted to USD 45.6, i.e. 11.2 dollars for high blood pressure, 3.8 dollars for
      diabetes, and 30.6 dollars for dyslipidemia (using generic drugs except for
      hypercholesterolemia). Cost for minimal follow-up medical care and laboratory
      tests amounted to 22.6 dollars. CONCLUSION: High prevalence of major risk factors
      was found in a rapidly developing country and costs for treatment needed to
      reduce risk factors in all high-risk individuals exceeded resources generally
      available in low or middle income countries. Our findings emphasize the need for
      affordable cost-effective treatment strategies and the critical importance of
      population strategies aimed at reducing risk factors in the entire population.

PMID- 16423281
TI  - WholePathwayScope: a comprehensive pathway-based analysis tool for high
      throughput data.
AB  - BACKGROUND: Analysis of High Throughput (HTP) Data such as microarray and
      proteomics data has provided a powerful methodology to study patterns of gene
      regulation at genome scale. A major unresolved problem in the post-genomic era is
      to assemble the large amounts of data generated into a meaningful biological
      context. We have developed a comprehensive software tool, WholePathwayScope
      (WPS), for deriving biological insights from analysis of HTP data. RESULT: WPS
      extracts gene lists with shared biological themes through color cue templates.
      WPS statistically evaluates global functional category enrichment of gene lists
      and pathway-level pattern enrichment of data. WPS incorporates well-known
      biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and
      Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant
      gene clusters or groups, and explores gene-term relationships within the derived
      gene-term association networks (GTANs). WPS simultaneously compares multiple
      datasets within biological contexts either as pathways or as association
      networks. WPS also integrates Genetic Association Database and Partial MedGene
      Database for disease-association information. We have used this program to
      analyze and compare microarray and proteomics datasets derived from a variety of
      biological systems. Application examples demonstrated the capacity of WPS to
      significantly facilitate the analysis of HTP data for integrative discovery.
      CONCLUSION: This tool represents a pathway-based platform for discovery
      integration to maximize analysis power. The tool is freely available at
      http://www.abcc.ncifcrf.gov/wps/wps_index.php.

PMID- 16423282
TI  - Transition into daylight saving time influences the fragmentation of the rest
      activity cycle.
AB  - BACKGROUND: Daylight saving time is widely adopted. Little is known about its
      influence on the daily rest-activity cycles. We decided to explore the effects of
      transition into daylight saving time on the circadian rhythm of activity.
      METHODS: We monitored the rest-activity cycles with the use of wrist-worn
      accelerometer on a sample of ten healthy adults for ten days around the
      transition into summer time. Identical protocols were carried out on the same
      individuals in two consecutive years, yielding data on 200 person-days for
      analysis in this study. RESULTS: There was no significant effect on the rest
      activity cycle in the sample as a whole. Fragmentation of the rest-activity cycle
      was enhanced in a subgroup of persons having sleep for eight hours or less (P =
      0.04) but reduced in those who preferred to sleep for more than eight hours per
      night (P = 0.05). The average level of motor activity was increased in persons
      having the morning preference for daily activity patterns (P = 0.01). CONCLUSION:
      Transition into daylight saving time may have a disruptive effect on the rest
      activity cycle in those healthy adults who are short-sleepers or more of the
      evening type.

PMID- 16423283
TI  - Phosphodiesterase type 4 expression and anti-proliferative effects in human
      pulmonary artery smooth muscle cells.
AB  - BACKGROUND: Pulmonary arterial hypertension is a proliferative vascular disease,
      characterized by aberrant regulation of smooth muscle cell proliferation and
      apoptosis in distal pulmonary arteries. Prostacyclin (PGI2) analogues have anti
      proliferative effects on distal human pulmonary artery smooth muscle cells
      (PASMCs), which are dependent on intracellular cAMP stimulation. We therefore
      sought to investigate the involvement of the main cAMP-specific enzymes,
      phosphodiesterase type 4 (PDE4), responsible for cAMP hydrolysis. METHODS: Distal
      human PASMCs were derived from pulmonary arteries by explant culture (n = 14,
      passage 3-12). Responses to platelet-derived growth factor-BB (5-10 ng/ml),
      serum, PGI2 analogues (cicaprost, iloprost) and PDE4 inhibitors (roflumilast,
      rolipram, cilomilast) were determined by measuring cAMP phosphodiesterase
      activity, intracellular cAMP levels, DNA synthesis, apoptosis (as measured by DNA
      fragmentation and nuclear condensation) and matrix metalloproteinase-2 and -9
      (MMP-2, MMP-9) production. RESULTS: Expression of all four PDE4A-D genes was
      detected in PASMC isolates. PDE4 contributed to the main proportion (35.9 +/-
      2.3%, n = 5) of cAMP-specific hydrolytic activity demonstrated in PASMCs,
      compared to PDE3 (21.5 +/- 2.5%), PDE2 (15.8 +/- 3.4%) or PDE1 activity (14.5 +/-
      4.2%). Intracellular cAMP levels were increased by PGI2 analogues and further
      elevated in cells co-treated with roflumilast, rolipram and cilomilast. DNA
      synthesis was attenuated by 1 microM roflumilast (49 +/- 6% inhibition), rolipram
      (37 +/- 6%) and cilomilast (30 +/- 4%) and, in the presence of 5 nM cicaprost,
      these compounds exhibited EC50 values of 4.4 (2.6-6.1) nM (Mean and 95%
      confidence interval), 59 (36-83) nM and 97 (66-130) nM respectively. Roflumilast
      attenuated cell proliferation and gelatinase (MMP-2 and MMP-9) production and
      promoted the anti-proliferative effects of PGI2 analogues. The cAMP activators
      iloprost and forskolin also induced apoptosis, whereas roflumilast had no
      significant effect. CONCLUSION: PDE4 enzymes are expressed in distal human PASMCs
      and the effects of cAMP-stimulating agents on DNA synthesis, proliferation and
      MMP production is dependent, at least in part, on PDE4 activity. PDE4 inhibition
      may provide greater control of cAMP-mediated anti-proliferative effects in human
      PASMCs and therefore could prove useful as an additional therapy for pulmonary
      arterial hypertension.

PMID- 16423284
TI  - Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Streptozotocin-induced diabetes (STZ-D) in rats has been associated
      with carnitine deficiency, bradycardia and left ventricular enlargement. AIM: The
      purpose of this study was to determine whether oral carnitine supplementation
      would normalize carnitine levels and cardiac function in STZ-D rats. METHODS:
      Wistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age
      normal Wistar rats (24) were used for comparison. Echocardiograms were performed
      at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals.
      HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same
      times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received
      supplemental oral carnitine for 16 weeks. RESULTS: The heart rates for the STZ-D
      rats (290 +/- 19 bpm) were less than control rats (324 +/- 20 bpm) (p < 0.05).
      After 4 weeks of oral carnitine supplementation, the serum carnitine and heart
      rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart
      rates of all study animals, but the increase in STZ-D rats (141 +/- 8 bpm) was
      greater than controls (79 +/- 8 bpm) (p < 0.05). The heart rates of STZ-D rats
      given oral carnitine, however, were no different than controls (94 +/- 9 bpm).
      The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7
      +/- 0.5) was greater than control animals (2.2 +/- 0.3) (p < 0.05) after 18 weeks
      of diabetes. In contrast, the LVM/BW (2.3 +/- .2) of the STZ-D animals receiving
      supplemental carnitine was the same as the control animals at 18 weeks.
      CONCLUSION: Thus, supplemental oral carnitine in STZ-D rats normalized serum
      carnitine, heart rate regulation and left ventricular size. These findings
      suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic
      animal model.

PMID- 16423285
TI  - Modeling the cost effectiveness of injury interventions in lower and middle
      income countries: opportunities and challenges.
AB  - BACKGROUND: This paper estimates the cost-effectiveness of five interventions
      that could counter injuries in lower and middle income countries(LMICs): better
      traffic enforcement, erecting speed bumps, promoting helmets for bicycles,
      promoting helmets for motorcycles, and storing kerosene in child proof
      containers. METHODS: We adopt an ingredients based approach to form models of
      what each intervention would cost in 6 world regions over a 10 year period
      discounted at both 3% and 6% from both the governmental and societal
      perspectives. Costs are expressed in local currency converted into US $2001. Each
      of these interventions has been assessed for effectiveness in a LMIC in limited
      region, these effectiveness estimates have been used to form models of disability
      adjusted life years (DALYs) averted for various regions, taking account of
      regional differences in the baseline burden of injury. RESULTS: The interventions
      modeled in this paper have cost effectiveness ratios ranging from US $5 to $ 556
      per DALY averted depending on region. Depending on local acceptability thresholds
      many of them could be judged cost-effective relative to interventions that are
      already adopted. Enhanced enforcement of traffic regulations is the most cost
      effective interventions with an average cost per DALY of $64 CONCLUSION: Injury
      counter measures appear to be cost-effective based on models. More evaluations of
      real interventions will help to strengthen the evidence basis.

PMID- 16423286
TI  - Examination of actin and microtubule dependent APC localisations in living
      mammalian cells.
AB  - BACKGROUND: The trafficking of the adenomatous polyposis coli (APC) tumour
      suppressor protein in mammalian cells is a perennially controversial topic.
      Immunostaining evidence for an actin-associated APC localisation at intercellular
      junctions has been previously presented, though live imaging of mammalian
      junctional APC has not been documented. RESULTS: Using live imaging of
      transfected COS-7 cells we observed intercellular junction-associated pools of
      GFP-APC in addition to previously documented microtubule-associated GFP-APC and a
      variety of minor localisations. Although both microtubule and junction-associated
      populations could co-exist within individual cells, they differed in their
      subcellular location, dynamic behaviour and sensitivity to cytoskeletal poisons.
      GFP-APC deletion mutant analysis indicated that a protein truncated immediately
      after the APC armadillo repeat domain retained the ability to localise to
      adhesive membranes in transfected cells. Supporting this, we also observed
      junctional APC immunostaining in cultures of human colorectal cancer cell line
      that express truncated forms of APC. CONCLUSION: Our data indicate that APC can
      be found in two spatially separate populations at the cell periphery and these
      populations can co-exist in the same cell. The first localisation is highly
      dynamic and associated with microtubules near free edges and in cell vertices,
      while the second is comparatively static and is closely associated with actin at
      sites of cell-cell contact. Our imaging confirms that human GFP-APC possesses
      many of the localisations and behaviours previously seen by live imaging of
      Xenopus GFP-APC. However, we report the novel finding that GFP-APC puncta can
      remain associated with the ends of shrinking microtubules. Deletion analysis
      indicated that the N-terminal region of the APC protein mediated its junctional
      localisation, consistent with our observation that truncated APC proteins in
      colon cancer cell lines are still capable of localising to the cell cortex. This
      may have implications for the development of colorectal cancer.

PMID- 16423287
TI  - Weekly induction intraperitoneal chemotherapy after primary surgical
      cytoreduction in patients with advanced epithelial ovarian cancer.
AB  - BACKGROUND: Traditional intraperitoneal (IP) therapy administered simultaneously
      with intravenous (IV) chemotherapy in the primary setting has been well
      documented. This retrospective study was conducted to investigate the role of
      weekly IP therapy as an inducing intervention before front-line IV chemotherapy,
      particularly in patients with bulky residual disease after surgery. METHODS: A
      total of 426 patients with advanced ovarian cancer treated between 1990 and 1999,
      were reviewed. Follow-up data were available in 409 patients. Of whom, 230
      patients received postoperative weekly IP therapy with a median cycles of 4,
      other 179 patients who did not receive any IP therapy were used as the control
      group. RESULTS: The median age of the patients was 51 years (range, 20-77 years).
      One hundred eighty-nine patients with stage III disease and 41 patients with
      stage IV disease were treated with postoperative IP therapy, respectively.
      Complications and toxicity were observed in 68 patients (29.5%), but there were
      no grade 4 toxicities and no patients died of complications or toxicities. In
      patients with residual disease > 1 cm, the median survival of those with IP
      delivery of chemotherapy and those without was 21.6 months and 18.8 months,
      respectively (hazard ratio [HR]= 0.69, P = 0.02). Whereas, in patients with
      residual disease </= 1 cm, the median survival was 46.8 months and 37.6 months,
      respectively (HR= 0.73, P = 0.09). Multivariate analysis suggested that the
      factors age </= 60 years, stage III, IP therapy and paclitaxel as front-line
      chemotherapy were associated with a better prognosis for patients with advanced
      ovarian cancer. CONCLUSION: Weekly postoperative IP therapy as an inducing
      intervention is practical for both physicians and patients with acceptable
      complications and associated with a lengthened survival of patients with advanced
      ovarian cancer. Whether this arm can be used in lieu of a traditional one needs
      further randomized trial to confirm the preliminary results.

PMID- 16423288
TI  - Similarity-based gene detection: using COGs to find evolutionarily-conserved
      ORFs.
AB  - BACKGROUND: Experimental verification of gene products has not kept pace with the
      rapid growth of microbial sequence information. However, existing annotations of
      gene locations contain sufficient information to screen for probable errors.
      Furthermore, comparisons among genomes become more informative as more genomes
      are examined. We studied all open reading frames (ORFs) of at least 30 codons
      from the genomes of 27 sequenced bacterial strains. We grouped the potential
      peptide sequences encoded from the ORFs by forming Clusters of Orthologous Groups
      (COGs). We used this grouping in order to find homologous relationships that
      would not be distinguishable from noise when using simple BLAST searches.
      Although COG analysis was initially developed to group annotated genes, we
      applied it to the task of grouping anonymous DNA sequences that may encode
      proteins. RESULTS: "Mixed COGs" of ORFs (clusters in which some sequences
      correspond to annotated genes and some do not) are attractive targets when
      seeking errors of gene prediction. Examination of mixed COGs reveals some
      situations in which genes appear to have been missed in current annotations and a
      smaller number of regions that appear to have been annotated as gene loci
      erroneously. This technique can also be used to detect potential pseudogenes or
      sequencing errors. Our method uses an adjustable parameter for degree of
      conservation among the studied genomes (stringency). We detail results for one
      level of stringency at which we found 83 potential genes which had not previously
      been identified, 60 potential pseudogenes, and 7 sequences with existing gene
      annotations that are probably incorrect. CONCLUSION: Systematic study of sequence
      conservation offers a way to improve existing annotations by identifying
      potentially homologous regions where the annotation of the presence or absence of
      a gene is inconsistent among genomes.

PMID- 16423289
TI  - Food composition database development for between country comparisons.
AB  - Nutritional assessment by diet analysis is a two-stepped process consisting of
      evaluation of food consumption, and conversion of food into nutrient intake by
      using a food composition database, which lists the mean nutritional values for a
      given food portion. Most reports in the literature focus on minimizing errors in
      estimation of food consumption but the selection of a specific food composition
      table used in nutrient estimation is also a source of errors. We are conducting a
      large prospective study internationally and need to compare diet, assessed by
      food frequency questionnaires, in a comparable manner between different
      countries. We have prepared a multi-country food composition database for
      nutrient estimation in all the countries participating in our study. The nutrient
      database is primarily based on the USDA food composition database, modified
      appropriately with reference to local food composition tables, and supplemented
      with recipes of locally eaten mixed dishes. By doing so we have ensured that the
      units of measurement, method of selection of foods for testing, and assays used
      for nutrient estimation are consistent and as current as possible, and yet have
      taken into account some local variations. Using this common metric for nutrient
      assessment will reduce differential errors in nutrient estimation and improve the
      validity of between-country comparisons.

PMID- 16423290
TI  - NOXclass: prediction of protein-protein interaction types.
AB  - BACKGROUND: Structural models determined by X-ray crystallography play a central
      role in understanding protein-protein interactions at the molecular level.
      Interpretation of these models requires the distinction between non-specific
      crystal packing contacts and biologically relevant interactions. This has been
      investigated previously and classification approaches have been proposed.
      However, less attention has been devoted to distinguishing different types of
      biological interactions. These interactions are classified as obligate and non
      obligate according to the effect of the complex formation on the stability of the
      protomers. So far no automatic classification methods for distinguishing
      obligate, non-obligate and crystal packing interactions have been made available.
      RESULTS: Six interface properties have been investigated on a dataset of 243
      protein interactions. The six properties have been combined using a support
      vector machine algorithm, resulting in NOXclass, a classifier for distinguishing
      obligate, non-obligate and crystal packing interactions. We achieve an accuracy
      of 91.8% for the classification of these three types of interactions using a
      leave-one-out cross-validation procedure. CONCLUSION: NOXclass allows the
      interpretation and analysis of protein quaternary structures. In particular, it
      generates testable hypotheses regarding the nature of protein-protein
      interactions, when experimental results are not available. We expect this server
      will benefit the users of protein structural models, as well as protein
      crystallographers and NMR spectroscopists. A web server based on the method and
      the datasets used in this study are available at http://noxclass.bioinf.mpi
      inf.mpg.de/.

PMID- 16423291
TI  - Major depression, fibromyalgia and labour force participation: a population-based
      cross-sectional study.
AB  - BACKGROUND: Previous studies have documented an elevated frequency of depressive
      symptoms and disorders in fibromyalgia, but have not examined the association
      between this comorbidity and occupational status. The purpose of this study was
      to describe these epidemiological associations using a national probability
      sample. METHODS: Data from iteration 1.1 of the Canadian Community Health Survey
      (CCHS) were used. The CCHS 1.1 was a large-scale national general health survey.
      The prevalence of major depression in subjects reporting that they had been
      diagnosed with fibromyalgia by a health professional was estimated, and then
      stratified by demographic variables. Logistic regression models predicting labour
      force participation were also examined. RESULTS: The annual prevalence of major
      depression was three times higher in subjects with fibromyalgia: 22.2% (95% CI
      19.4 - 24.9), than in those without this condition: 7.2% (95% CI 7.0 - 7.4). The
      association persisted despite stratification for demographic variables. Logistic
      regression models predicting labour force participation indicated that both
      conditions had an independent (negative) effect on labour force participation.
      CONCLUSION: Fibromyalgia and major depression commonly co-occur and may be
      related to each other at a pathophysiological level. However, each syndrome is
      independently and negatively associated with labour force participation. A
      strength of this study is that it was conducted in a large probability sample
      from the general population. The main limitations are its cross-sectional nature,
      and its reliance on self-reported diagnoses of fibromyalgia.

PMID- 16423292
TI  - A global definition of expression context is conserved between orthologs, but
      does not correlate with sequence conservation.
AB  - BACKGROUND: The massive scale of microarray derived gene expression data allows
      for a global view of cellular function. Thus far, comparative studies of gene
      expression between species have been based on the level of expression of the gene
      across corresponding tissues, or on the co-expression of the gene with another
      gene. RESULTS: To compare gene expression between distant species on a global
      scale, we introduce the "expression context". The expression context of a gene is
      based on the co-expression with all other genes that have unambiguous
      counterparts in both genomes. Employing this new measure, we show 1) that the
      expression context is largely conserved between orthologs, and 2) that sequence
      identity shows little correlation with expression context conservation after gene
      duplication and speciation. CONCLUSION: This means that the degree of sequence
      identity has a limited predictive quality for differential expression context
      conservation between orthologs, and thus presumably also for other facets of gene
      function.

PMID- 16423295
TI  - The Farmer Field School: a method for enhancing the role of rural communities in
      malaria control ?
AB  - Malaria has strong linkages with agriculture, and farmers in malarious regions
      have a central position in creating or controlling the conditions that favour
      disease transmission. An interdisciplinary and integrated approach is needed to
      involve farmers and more than one sector in control efforts. It is suggested that
      malaria control can benefit from a complementary intervention in rural
      development, the Farmer Field School (FFS) on Integrated Pest Management (IPM).
      This is a form of education that uses experiential learning methods to build
      farmers' expertise, and has proven farm-level and empowerment effects. The
      benefits of incorporating malaria control into the IPM curriculum are discussed.
      An example of a combined health-agriculture curriculum, labeled Integrated Pest
      and Vector Management (IPVM), developed in Sri Lanka is presented. Institutional
      ownership and support for IPVM could potentially be spread over several public
      sectors requiring a process for institutional learning and reform.

PMID- 16423293
TI  - Health-related quality of life in patients waiting for major joint replacement. A
      comparison between patients and population controls.
AB  - BACKGROUND: Several quality-of-life studies in patients awaiting major joint
      replacement have focused on the outcomes of surgery. Interest in examining
      patients on the elective waiting list has increased since the beginning of 2000.
      We assessed health-related quality of life (HRQoL) in patients waiting for total
      hip (THR) or knee (TKR) replacement in three Finnish hospitals, and compared
      patients' HRQoL with that of population controls. METHODS: A total of 133
      patients awaiting major joint replacement due to osteoarthritis (OA) of the hip
      or knee joint were prospectively followed from the time the patient was placed on
      the waiting list to hospital admission. A sample of controls matched by age,
      gender, housing and home municipality was drawn from the computerised population
      register. HRQoL was measured by the generic 15D instrument. Differences between
      patients and the population controls were tested by the independent samples t
      test and between the measurement points by the paired samples t-test. A linear
      regression model was used to explain the variance in the 15D score at admission.
      RESULTS: At baseline, 15D scores were significantly different between patients
      and the population controls. Compared with the population controls, patients were
      worse off on the dimensions of moving (P < 0.001), sleeping (P < 0.001), sexual
      activity (P < 0.001), vitality (P < 0.001), usual activities (P < 0.001) and
      discomfort and symptoms (P < 0.001). Further, psychological factors--depression
      (P < 0.001) and distress (P = 0.004)--were worse among patients than population
      controls. The patients showed statistically significantly improved average scores
      at admission on the dimensions of moving (P = 0.026), sleeping (P = 0.004) and
      discomfort and symptoms (P = 0.041), but not in the overall 15D score compared
      with the baseline. In patients, 15D score at baseline (P < 0.001) and body mass
      index (BMI) (P = 0.020) had an independent effect on patients' 15D score at
      hospital admission. CONCLUSION: Although patients' HRQoL did not deteriorate
      while waiting, a consistently worse HRQoL was observed in patients waiting for
      major joint replacement compared with population controls.

PMID- 16423294
TI  - Mucociliary and long-term particle clearance in airways of patients with immotile
      cilia.
AB  - Spherical monodisperse ferromagnetic iron oxide particles of 1.9 microm geometric
      and 4.2 microm aerodynamic diameter were inhaled by seven patients with primary
      ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13
      healthy non-smokers (NS) from a previous study. The bolus penetration front depth
      was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/
      8 % after 8 s breath holding time. Particle retention was measured by the
      magnetopneumographic method over a period of nine months. Particle clearance from
      the airways showed a fast and a slow phase. In PCD patients airway clearance was
      retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time
      of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time
      of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast
      phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact
      mucociliary clearance. There was no difference in the slow clearance phase
      between PCD patients and healthy NS. Despite non-functioning cilia the
      effectiveness of airway clearance in PCD patients is comparable to healthy NS,
      with a prolonged kinetics of one week, which may primarily reflect the
      effectiveness of cough clearance. This prolonged airway clearance allows longer
      residence times of bacteria and viruses in the airways and may be one reason for
      increased frequency of infections in PCD patients.

PMID- 16423296
TI  - Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of
      comparative genomic hybridization results.
AB  - Nasopharyngeal carcinoma (NPC) is a highly prevalent disease in Southeast Asia
      and its prevalence is clearly affected by genetic background. Various theories
      have been suggested for its high incidence in this geographical region but to
      these days no conclusive explanation has been identified. Chromosomal imbalances
      identifiable through comparative genomic hybridization may shed some light on
      common genetic alterations that may be of relevance to the onset and progression
      of NPC. Review of the literature, however, reveals contradictory results among
      reported findings possibly related to factors associated with patient selection,
      stage of disease, differences in methodological details etc. To increase the
      power of the analysis and attempt to identify commonalities among the reported
      findings, we performed a meta-analysis of results described in NPC tissues based
      on chromosomal comparative genomic hybridization (CGH). This meta-analysis
      revealed consistent patters in chromosomal abnormalities that appeared to cluster
      in specific "hot spots" along the genome following a stage-dependent progression.

PMID- 16423297
TI  - Urbanization and traffic related exposures as risk factors for schizophrenia.
AB  - BACKGROUND: Urban birth or upbringing increase schizophrenia risk. Though
      unknown, the causes of these urban-rural differences have been hypothesized to
      include, e.g., infections, diet, toxic exposures, social class, or an artefact
      due to selective migration. METHODS: We investigated the hypothesis that traffic
      related exposures affect schizophrenia risk and that this potential effect is
      responsible for the urban-rural differences. The geographical distance from place
      of residence to nearest major road was used as a proxy variable for traffic
      related exposures. We used a large population-based sample of the Danish
      population (1.89 million people) including information on all permanent addresses
      linked with geographical information on all roads and house numbers in Denmark.
      Schizophrenia in cohort members (10,755 people) was identified by linkage with
      the Danish Psychiatric Central Register. RESULTS: The geographical distance from
      place of residence to nearest major road had a significant effect. The highest
      risk was found in children living 500-1000 metres from nearest major road (RR =
      1.30 (95% Confidence Interval: 1.17-1.44). However, when we accounted for the
      degree of urbanization, the geographical distance to nearest major road had no
      significant effect. CONCLUSION: The cause(s) or exposure(s) responsible for the
      urban-rural differences in schizophrenia risk were closer related to the degree
      of urbanization than to the geographical distance to nearest major road. Traffic
      related exposures might thus be less likely explanations for the urban-rural
      differences in schizophrenia risk.

PMID- 16423298
TI  - Short forms of the Child Perceptions Questionnaire for 11-14-year-old children
      (CPQ11-14): development and initial evaluation.
AB  - BACKGROUND: The Child Perceptions Questionnaire for children aged 11 to 14 years
      (CPQ11-14) is a 37-item measure of oral-health-related quality of life (OHRQoL)
      encompassing four domains: oral symptoms, functional limitations, emotional and
      social well-being. To facilitate its use in clinical settings and population
      based health surveys, it was shortened to 16 and 8 items. Item impact and
      stepwise regression methods were used to produce each version. This paper
      describes the developmental process, compares the discriminative properties of
      the resulting four short-forms and evaluates their precision relative to the
      original CPQ11-14. METHODS: The item impact method used data from the CPQ11-14
      item reduction study to select the questions with the highest impact scores in
      each domain. The regression method, where the dependent variable was the overall
      CPQ11-14 score and the independent variables its individual questions, was
      applied to the data collected in the validity study for the CPQ11-14. The
      measurement properties (i.e. criterion validity, construct validity, internal
      consistency reliability and test-retest reliability) of all 4 short-forms were
      evaluated using the data from the validity and reliability studies for the CPQ11
      14. RESULTS: All short forms detected substantial variability in children's
      OHRQoL. The mean scores on the two 16-item questionnaires were almost identical,
      while on the two 8-item questionnaires they differed by only one score point. The
      mean scores standardized to 0-100 were higher on the short forms than the
      original CPQ11-14 (p < 0.001). There were strong significant correlations between
      all short-form scores and CPQ11-14 scores (0.87-0.98; p < 0.001). Hypotheses
      concerning construct validity were confirmed: the short-forms' scores were
      highest in the oro-facial, lower in the orthodontic and lowest in the paediatric
      dentistry group; all short-form questionnaires were positively correlated with
      the ratings of oral health and overall well-being, with the correlation
      coefficient being higher for the latter. The relative validity coefficients were
      0.85 to 1.18. Cronbach's alpha and intraclass correlation coefficients ranged
      0.71-0.83 and 0.71-0.77, respectively. CONCLUSION: All short forms demonstrated
      excellent criterion validity and good construct validity. The reliability
      coefficients exceeded standards for group-level comparisons. However, these are
      preliminary findings based on the convenience sampling and further testing in
      replicated studies involving clinical and general samples of children in various
      settings is necessary to establish measurement sensitivity and discriminative
      properties of these questionnaires.

PMID- 16423300
TI  - A new pooling strategy for high-throughput screening: the Shifted Transversal
      Design.
AB  - BACKGROUND: In binary high-throughput screening projects where the goal is the
      identification of low-frequency events, beyond the obvious issue of efficiency,
      false positives and false negatives are a major concern. Pooling constitutes a
      natural solution: it reduces the number of tests, while providing critical
      duplication of the individual experiments, thereby correcting for experimental
      noise. The main difficulty consists in designing the pools in a manner that is
      both efficient and robust: few pools should be necessary to correct the errors
      and identify the positives, yet the experiment should not be too vulnerable to
      biological shakiness. For example, some information should still be obtained even
      if there are slightly more positives or errors than expected. This is known as
      the group testing problem, or pooling problem. RESULTS: In this paper, we present
      a new non-adaptive combinatorial pooling design: the "shifted transversal design"
      (STD). It relies on arithmetics, and rests on two intuitive ideas: minimizing the
      co-occurrence of objects, and constructing pools of constant-sized intersections.
      We prove that it allows unambiguous decoding of noisy experimental observations.
      This design is highly flexible, and can be tailored to function robustly in a
      wide range of experimental settings (i.e., numbers of objects, fractions of
      positives, and expected error-rates). Furthermore, we show that our design
      compares favorably, in terms of efficiency, to the previously described non
      adaptive combinatorial pooling designs. CONCLUSION: This method is currently
      being validated by field-testing in the context of yeast-two-hybrid interactome
      mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer
      Institute. Many similar projects could benefit from using the Shifted Transversal
      Design.

PMID- 16423299
TI  - Referrals from general practice to consultants in Germany: if the GP is the
      initiator, patients' experiences are more positive.
AB  - BACKGROUND: Referrals of patients from primary care to medical specialist care
      are an important activity in any health care system. German data show that the
      number of referrals by GPs have increased since 2004, but detailed insight into
      the experiences of patients, GPs and consultants regarding referrals is very
      limited. This study aimed at describing the experiences of consultants, GPs and
      patients with referrals from primary care to medical specialist care. An
      additional objective was to examine the impact of purpose regarding the referral
      and of the referrer on the experiences of GPs and patients. METHODS: Referrals of
      26 general practitioners (GPs) from 25 practices in Marbach, a rural region in
      the south of Germany were studied. All adult patients referred after consulting
      these GPs in a period of five weeks were eligible for the study. GPs, consultants
      and patients completed short structured forms to document factual characteristics
      of each referral and their experiences with the referral. GPs and patients
      completed forms before and after the referral was made, while the consultants
      completed forms after the patient had consulted them. RESULTS: Overall,
      consultants were very positive about appropriateness of the referral (91%). They
      were somewhat more critical regarding the information provided on the patients'
      medical history (61%) and prescriptions (48%). In 258 referrals (63%) GPs
      perceived clear diagnostic benefits, while in 202 referrals (49%) they perceived
      clear treatment benefits. GPs' experiences were more positive if the GP's purpose
      was to reduce diagnostic uncertainty (beta = 0.318, p < 0.001) or if the purpose
      was to exclude serious illness (beta = 0.143, p < 0.010). Other purposes of the
      referral had no impact on their experiences. Patients' expectations regarding the
      referrals mostly referred to diagnosis, including increased diagnostic certainty
      (80%), detailed information about the illness (66%) and exclusion of serious
      illness (62%). They were overall satisfied with the referral (83%). Their
      experiences with the referral were more positive if the initiative for the
      referral came from the physician (beta = 0.365, p < 0.000). CONCLUSION: Patients,
      GPs and consultants have positive views on the value of referrals from primary
      care to medical specialists. Patients were most positive if the physician had
      initiated the referral, which supports the gate keeper role of the GP.

PMID- 16423301
TI  - A need to study the immune status of frail older adults.

PMID- 16423302
TI  - Improvement in hearing after chiropractic care: a case series.
AB  - BACKGROUND: The first chiropractic adjustment given in 1895 was reported to have
      cured deafness. This study examined the effects of a single, initial chiropractic
      visit on the central nervous system by documenting clinical changes of audiometry
      in patients after chiropractic care. CASE PRESENTATION: Fifteen patients are
      presented (9 male, 6 female) with a mean age of 54.3 (range 34-71). A Welch Allyn
      AudioScope 3 was used to screen frequencies of 1000, 2000, 4000 and 500 Hz
      respectively at three standard decibel levels 20 decibels (dB), 25 dB and 40 dB,
      respectively, before and immediately after the first chiropractic intervention.
      Several criteria were used to determine hearing impairment. Ventry & Weinstein
      criteria of missing one or more tones in either ear at 40 dB and Speech-frequency
      criteria of missing one or more tones in either ear at 25 dB. All patients were
      classified as hearing impaired though greater on the right. At 40 dB using the
      Ventry & Weinstein criteria, 6 had hearing restored, 7 improved and 2 had no
      change. At 25 dB using the Speech-frequency criteria, none were restored, 11
      improved, 4 had no change and 3 missed a tone. CONCLUSION: A percentage of
      patients presenting to the chiropractor have a mild to moderate hearing loss,
      most notably in the right ear. The clinical progress documented in this report
      suggests that manipulation delivered to the neuromusculoskeletal system may
      create central plastic changes in the auditory system.

PMID- 16423303
TI  - Highly sensitive real-time PCR for specific detection and quantification of
      Coxiella burnetii.
AB  - BACKGROUND: Coxiella burnetii, the bacterium causing Q fever, is an obligate
      intracellular biosafety level 3 agent. Detection and quantification of these
      bacteria with conventional methods is time consuming and dangerous. During the
      last years, several PCR based diagnostic assays were developed to detect C.
      burnetii DNA in cell cultures and clinical samples. We developed and evaluated
      TaqMan-based real-time PCR assays that targeted the singular icd (isocitrate
      dehydrogenase) gene and the transposase of the IS1111a element present in
      multiple copies in the C. burnetii genome. RESULTS: To evaluate the precision of
      the icd and IS1111 real-time PCR assays, we performed different PCR runs with
      independent DNA dilutions of the C. burnetii Nine Mile RSA493 strain. The results
      showed very low variability, indicating efficient reproducibility of both assays.
      Using probit analysis, we determined that the minimal number of genome
      equivalents per reaction that could be detected with a 95% probability was 10 for
      the icd marker and 6.5 for the IS marker. Plasmid standards with cloned icd and
      IS1111 fragments were used to establish standard curves which were linear over a
      range from 10 to 10(7) starting plasmid copy numbers. We were able to quantify
      cell numbers of a diluted, heat-inactivated Coxiella isolate with a detection
      limit of 17 C. burnetii particles per reaction. Real-time PCR targeting both
      markers was performed with DNA of 75 different C. burnetii isolates originating
      from all over the world. Using this approach, the number of IS1111 elements in
      the genome of the Nine Mile strain was determined to be 23, close to 20, the
      number revealed by genome sequencing. In other isolates, the number of IS1111
      elements varied widely (between seven and 110) and seemed to be very high in some
      isolates. CONCLUSION: We validated TaqMan-based real-time PCR assays targeting
      the icd and IS1111 markers of C. burnetii. The assays were shown to be specific,
      highly sensitive and efficiently reproducible. Cell numbers in dilutions of a C.
      burnetii isolate were reliably quantified. PCR quantification suggested a high
      variability of the number of IS1111 elements in different C. burnetii isolates,
      which may be useful for further phylogenetic studies.

PMID- 16423304
TI  - Recrafting the neighbor-joining method.
AB  - BACKGROUND: The neighbor-joining method by Saitou and Nei is a widely used method
      for constructing phylogenetic trees. The formulation of the method gives rise to
      a canonical Theta(n3) algorithm upon which all existing implementations are
      based. RESULTS: In this paper we present techniques for speeding up the canonical
      neighbor-joining method. Our algorithms construct the same phylogenetic trees as
      the canonical neighbor-joining method. The best-case running time of our
      algorithms are O(n2) but the worst-case remains O(n3). We empirically evaluate
      the performance of our algoritms on distance matrices obtained from the Pfam
      collection of alignments. The experiments indicate that the running time of our
      algorithms evolve as Theta(n2) on the examined instance collection. We also
      compare the running time with that of the QuickTree tool, a widely used efficient
      implementation of the canonical neighbor-joining method. CONCLUSION: The
      experiments show that our algorithms also yield a significant speed-up, already
      for medium sized instances.

PMID- 16423305
TI  - Segregation analysis of apolipoprotein A1 levels in families of adolescents: a
      community-based study in Taiwan.
AB  - BACKGROUND: Apolipoprotein (Apo) A1 is a protective factor for cardiovascular
      events. This study aimed to perform complex segregation analyses of Apo A1 levels
      in families of adolescents systematically ascertained from the junior high school
      students in a rural community. Both siblings and parents of the adolescent
      probands were recruited for the study. Apo A1 concentrations were measured by
      turbidimetric immunoassay methods. After adjustment for gender, age, body mass
      index, smoking and drinking status, residual values of Apo A1 were subjected to
      subsequent analyses. RESULTS: Significant mother-father and parent-offspring
      correlations were found. Commingling analyses indicated that a four-component
      distribution model was needed to account for the Apo A1 variation. Segregation
      analysis using regressive models revealed that the best-fit model of Apo A1 was a
      model of environmental effect plus familial correlation (heritability = 23.9%),
      in which a significant mother-father correlation existed. Models containing major
      gene effect could be rejected. CONCLUSION: These results suggest that variations
      of Apo A1 levels in the normal range, especially during adolescence, are likely
      to be influenced by multiple factors without significant contribution from major
      genes.

PMID- 16423306
TI  - Effect of prolonged HAART on oral colonization with Candida and candidiasis.
AB  - BACKGROUND: Progressive cell-mediated immunodeficiency with decrease of CD4+
      lymphocyte count to less than or equal to 200 cells/mm3 is a major risk factor
      for colonization with Candida species and development of candidiasis.
      Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus
      (HIV)-infected patients during the course of the disease. This study is to
      determine the effect of prolonged highly active antiretroviral therapy (HAART) on
      oropharyngeal colonization with Candida species and oral candidiasis. METHODS: A
      prospective, longitudinal follow-up study in HIV-infected patients receiving
      HAART. RESULTS: The mean CD4+ count increased from 232.5 to 316 cells/mm3 and the
      proportion of patients whose CD4+ count less than 200 cells/mm3 decreased from
      50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The
      prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The
      decrease in Candida colonization was less impressive, falling from 57.8% to 46.5
      % (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%)
      remained colonized with Candida and 42 (29.6%) remained negative. In the
      remaining 52 patients, 34 switched from culture positive to negative, and an
      increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients
      who switched from culture negative to positive, 61.1% also demonstrated an
      increase in CD4+ lymphocyte count (p = 0.01). CONCLUSION: These findings indicate
      that HAART is highly effective in decreasing oral candidiasis in association with
      a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating
      Candida from the oropharynx.

PMID- 16423307
TI  - The contribution of microscopy to targeting antimalarial treatment in a low
      transmission area of Tanzania.
AB  - BACKGROUND: There is a need for improved targeting of antimalarial treatment if
      artemisinin combination therapy is to be successfully introduced in Africa. This
      study aimed to explore why malaria slides are requested and how their results
      guide treatment decisions in an area of low transmission of P. falciparum.
      METHODS: Outpatients attending a district hospital in a highland area of Tanzania
      were studied over a 3-week period. Clinical and social data were collected from
      patients who had been prescribed an antimalarial or sent for a malaria slide.
      Hospital slides were re-read later by research methods. RESULTS: Of 1,273
      consultations 132(10%) were treated presumptively for malaria and 214(17%) were
      sent for a malaria slide; only 13(6%) of these were reported positive for P.
      falciparum but 96(48%) of the 201 slide-negative cases were treated for malaria
      anyway. In a logistic regression model, adults (OR 3.86, P < 0.01), a history of
      fever (OR1.72, P = 0.03) and a longer travel time to the clinic (OR 1.77 per hour
      travelled, P < 0.01) independently predicted the request for a malaria slide.
      Only a history of a cough predicted (negatively) the prescription of an
      antimalarial with a negative slide result (OR 0.44, P < 0.01). The sensitivity
      and specificity of hospital slide results were 50% and 96% respectively.
      CONCLUSION: Progress in targeting of antimalarials in low malaria transmission
      settings is likely to depend on consistent use of malaria microscopy and on the
      willingness of health workers to be guided by negative slide results. Further
      studies are needed to identify how this can be achieved.

PMID- 16423308
TI  - Eye care utilization patterns in Tehran population: a population based cross
      sectional study.
AB  - BACKGROUND: The aim of this study is to determine eye care visits which are an
      indicator of eye care service utilization by Tehran population and its
      determinants. METHODS: Through a population-based, cross-sectional study, 6497
      Tehran citizens were sampled. All participants had complete eye examinations and
      an interview regarding demographic and socioeconomic status variables, past
      medical and eye history, and their previous and last eye care visits. RESULTS:
      Among those sampled, 4565 people participated in the study (response rate of
      70.3%). Among these participants, 34.7 % had never visited an ophthalmologist or
      optometrist (95% confidence interval [CI]: 32.4 to 36.9) and 43.2% had not seen
      an eye care provider in the last 5 years. Multivariate logistic regression
      revealed that men (OR = 1.30), younger participants (each year increase in age:
      OR = 0.98) and the less educated (each year increase in education: OR = 0.93)
      were more likely, and the visually impaired were less likely (OR = 0.41) to have
      neglected eye care. CONCLUSION: A large proportion of the population, including
      those in the high risk group who require eye care, has never utilized any eye
      care service. These data suggest that efforts have to be made to better
      understand the causes and to optimize the utilization of the available eye care
      services in the population.

PMID- 16423309
TI  - Diagnosis and treatment of ileal pouch diseases in patients with underlying
      ulcerative colitis.
AB  - Ileal pouch-anal anastomosis (IPAA) after total proctocolectomy is the surgical
      treatment of choice for ulcerative colitis (UC) patients with medically
      refractory disease or dysplasia. IPAA significantly improves quality of life in
      UC patients who require surgery. However, certain inflammatory and
      noninflammatory diseases can develop after the surgery, including pouchitis,
      Crohn's disease (CD) of the pouch, cuffitis, and irritable pouch syndrome. The
      cause and pathogenesis of these disease conditions of IPAA are largely unknown.
      Accurate diagnosis and classification are important for appropriate management.

PMID- 16423310
TI  - Travelers' diarrhea: modern concepts and new developments.
AB  - Travelers' diarrhea occurs when persons move from industrialized regions to
      developing countries with reduced hygiene. Bacterial enteropathogens from
      ingested food are the primary causes. Although it is possible to reduce the
      occurrence of illness by careful selection of food and beverages, travelers do
      not seem willing to restrict their diets. Diarrhea is associated with a
      disability of 24 hours per episode, interfering with travel plans and, of even
      greater concern, post-diarrhea irritable bowel syndrome (IBS) occurs in up to 10%
      of patients. The use of rifaximin, a poorly absorbed drug, is likely to become
      common as an attempt to prevent diarrhea and post-infectious IBS. All travelers
      to high-risk areas should take with them an effective antibacterial drug
      (rifaximin, fluoroquinolones, or azithromycin) for self-treatment of diarrhea
      occurring during travel. Additional work is needed to improve the hygienic
      conditions found in the developing world into which susceptible persons travel.

PMID- 16423311
TI  - Diarrhea in patients with AIDS.
AB  - Diarrhea in patients with AIDS is a worldwide problem that can have a devastating
      impact on quality of life for the patient. Chronic diarrhea, usually defined as
      at least 4 weeks' duration, is more common in patients with low CD4-positive T
      lymphocyte counts, signaling advanced immunosuppression. Some organisms, such as
      Microsporidia, usually cause diarrhea only in the immunosuppressed; others, such
      as Cryptosporidium, Salmonella, Shigella, and Campylobacter, which are capable of
      causing diarrhea in the immunocompetent population, produce more severe or
      prolonged infections in people living with AIDS. Familiarity with the most common
      pathogens in the clinician's region will help with diagnosis and treatment.
      Because treatment options vary widely depending upon the infectious agent,
      thorough microbiologic evaluation is warranted. A stepped diagnostic approach of
      stool cultures and specialized microscopy and stains for protozoa, followed by
      sigmoidoscopy or colonoscopy and duodenoscopy with biopsies for histopathological
      examination is recommended in all patients with persistent, disabling diarrhea
      who have a CD4 count of less than 200/mm3, and should be considered for those
      with higher counts on an individual basis. Treatment, tailored to the specific
      pathogen, may need to be prolonged in the most severely immunocompromised
      patients to prevent relapse or recrudescence. For patients taking antiretroviral
      therapy (especially protease inhibitors) in whom no infectious agent can be
      found, diarrhea may be due to the medications. Nonspecific antidiarrheal agents
      should be tried until one that suits the patient is found. The most essential
      component of any therapeutic strategy for a patient with AIDS-associated diarrhea
      is restoration of the underlying immunologic defect using highly active
      antiretroviral therapy.

PMID- 16423312
TI  - Ileostomy diarrhea.
AB  - Ileostomy diarrhea is not an uncommon problem and can lead to considerable loss
      of quality of life. Unfortunately, well-designed therapeutic trials are lacking,
      and thus, treatment of patients with ileostomy diarrhea remains largely empiric.
      The majority of individuals will have "idiopathic" ileostomy diarrhea, or
      increased output due to proctocolectomy with limited ileal resection alone. Once
      other, less common causes are excluded, empiric treatment should be initiated
      with the safest, least costly option. In general, this consists of a dietary
      evaluation and symptomatic treatment with loperamide and advancing as needed to
      other, more expensive options, frequently with an increase in side effect
      profile. Other more recently evaluated treatment options include budesonide and
      oleic acid; however, efficacy has only been demonstrated in preliminary studies;
      further evaluation is needed. Limited data exist regarding success of surgical
      therapy such as reversed peristaltic ileal segments. It remains to be seen if
      surgery, other than ileostomy revision, has a role in the treatment of ileostomy
      diarrhea.

PMID- 16423313
TI  - Treatment of noncardiac chest pain of psychological origin.
AB  - Psychiatric comorbidity is not an uncommon phenomenon in patients with noncardiac
      chest pain (NCCP). Panic disorder seems to be the most important psychiatric
      comorbidity for a number of reasons. First, it is the most common psychiatric
      disorder associated with NCCP. Second, panic disorder is a highly treatable
      condition that can produce dramatic improvement of NCCP when treatment is
      appropriate. Finally, the treatment of psychiatric comorbidity, whether panic
      disorder or other psychiatric disorders, can pay significant dividends in terms
      of improving the patient's overall well-being and adaptation to illness, even if
      his/her chest pain symptoms are not alleviated. Adopting a biopsychosocial model
      to intervene on the stress of these patients' experience is a key concept that
      can make NCCP a much less formidable challenge for the gastroenterologist.

PMID- 16423314
TI  - Endoscopic therapy for GERD: is the evidence for efficacy any stronger?
AB  - Gastroesophageal reflux disease (GERD) is a common chronic medical disorder that
      has a significant impact on quality of life and afflicts millions of people
      worldwide. Therapy with either daily medications or surgical fundoplication,
      though highly effective for the majority of patients, is not without long-term
      shortcomings. The development of endoscopic antireflux therapies has been fueled
      by the hope of providing safe, effective, long-term symptomatic relief. Although
      several studies have been published, they are limited by small sample size, lack
      of adequate controls, and a highly selective patient population. However, it is
      clear that many, if not most, patients will continue to be on acid-suppressive
      therapy despite these procedures. Also, reports of postmarketing adverse effects
      emphasize the need for further scrutiny of the safety of these devices. This
      review will summarize the available evidence and provide tentative conclusions
      about the current and evolving role of endoscopic antireflux therapy.

PMID- 16423315
TI  - Reflux-induced laryngitis (laryngopharyngeal reflux).
AB  - Gastroesophageal reflux disease (GERD) has been increasingly associated with ear,
      nose, and throat (ENT) signs and symptoms. This condition, often referred to as
      laryngopharyngeal reflux (LPR) has become increasingly prevalent. However, the
      cause and effect relationship between GERD and laryngeal signs or symptoms is far
      from established. Many patients diagnosed initially with GERD as the cause of
      laryngeal signs do not symptomatically or laryngoscopically respond to aggressive
      acid suppression and do not have abnormal esophageal acid exposure by pH
      monitoring. This has resulted in frustration on the part of both
      gastroenterologists and ENT physicians and confusion on the part of patients. The
      current recommendations for the management of LPR patients call for initial
      empiric therapy with twice daily proton-pump inhibitors (PPIs) for 2 to 4 months.
      In those unresponsive to such therapy, diagnostic testing with prolonged pH
      monitoring may be indicated. However, in the majority of such patients, the
      reason for lack of response to PPI therapy may be irritation of the larynx by
      causes other than GERD. Surgical fundoplication in this group of patients has
      lower efficacy than in those with typical symptoms of GERD and is reserved for
      those with improvement on acid-suppressive therapy.

PMID- 16423316
TI  - Esophageal foreign bodies: types and techniques for removal.
AB  - Patients with esophageal foreign bodies require prompt diagnosis and therapy. The
      first tasks are to determine the type of object, time since ingestion, location
      of the object, and the likelihood of associated complications. Patients who have
      evidence of complete esophageal occlusion or who have ingested a sharp or pointed
      object require urgent treatment due to the increased risk of complications.
      Button batteries are particularly injurious in the esophagus and should be
      removed immediately. Coins in the esophagus should also be removed; however, a
      brief period of observation is appropriate for coins in the distal esophagus, as
      some will pass spontaneously. Flexible endoscopy is the therapeutic modality of
      choice for most patients. The key principles for endoscopic management of
      esophageal foreign bodies are to protect the airway, to maintain control of the
      object during extraction, and to avoid causing additional damage. Endotracheal
      intubation is sometimes necessary, especially in younger children and those at
      higher risk for aspiration. The use of devices such as an esophageal overtube and
      a latex protector hood may facilitate safer extraction of sharp/pointed objects.
      Patients with food impactions usually require treatment of an associated
      structural lesion of the esophagus.

PMID- 16423317
TI  - Esophagectomy for Barrett's esophagus: indications, techniques, and outcome.
AB  - Barrett's esophagus describes metaplastic changes from squamous mucosa to
      specialized columnar epithelium that can progress from low-grade dysplasia to
      high-grade dysplasia and even invasive carcinoma. The treatment of Barrett's
      esophagus with low-grade dysplasia or Barrett's adenocarcinoma is relatively
      standardized; however, controversy remains regarding appropriate therapy for
      Barrett's esophagus with high-grade dysplasia. Treatment recommendations for high
      grade dysplasia vary widely, from periodic endoscopic surveillance to endoscopic
      ablative therapies and esophagectomy. Selected studies have shown that a
      relatively high percentage (41% to 47%) of patients with high-grade dysplasia
      have occult carcinoma. In these patients, surgery is indicated, as esophagectomy
      can be curative for early stage adenocarcinoma in Barrett's esophagus. A major
      criticism of esophagectomy is the significant morbidity and mortality. Minimally
      invasive esophagectomy was developed in an effort to reduce the morbidity
      associated with open esophagectomy. In minimally invasive esophagectomy, the
      abdominal laparotomy is replaced with laparoscopy, and the conventional right
      thoracotomy is replaced with thoracoscopy to reduce the operative trauma. In
      experienced centers, minimally invasive esophagectomy is now an attractive
      alternative for the treatment of Barrett's esophagus with high-grade dysplasia.

PMID- 16423318
TI  - Small-area variations in conviction rates for DWI: the significance of contextual
      variables in a Southwestern state.
AB  - Average annual conviction rates (1990-2000) of people arrested for driving under
      the influence of alcohol in each of New Mexico's 33 counties are described.
      Conviction rates vary from 58 to 95%. Rates are correlated with political
      conservatism, being higher where a higher proportion of voters voted for the
      republican presidential candidates, and with measures of crowding in the courts.
      Conviction rates are higher in rural than urban areas and are correlated with a
      low prevalence of alcohol-related problems in the population. The variance in
      conviction rates is higher in rural than urban areas, and higher where measures
      of court crowding are low. The results suggest that political culture and the
      efficiency of court functioning are each independently associated with conviction
      rates for DWI and may also be associated in a reciprocal fashion with both low
      DWI arrest rates and alcohol-involved crash rates.

PMID- 16423319
TI  - Segment characteristics and severity of head-on crashes on two-lane rural
      highways in Maine.
AB  - More than two out of three of all fatal crashes in Maine occur on rural, two-lane
      collector or arterial roads. Head-on crashes on these roads account for less than
      5% of the crashes, but they are responsible for almost half of all fatalities.
      Data analyzed in this study was provided by Maine Department of Transportation
      and covers all head-on crashes for 2000-2002 during which period there were 3,136
      head-on crashes reported. Out of these, 127 were fatal crashes and 235 produced
      incapacitating but not fatal injuries. These two categories made up over 75% of
      the crash cost. A clear majority of head-on crashes on two-lane, rural roads in
      Maine were caused by drivers making errors or misjudging situations.
      Illegal/unsafe speed was a factor in 32% of the crashes while driver
      inattention/distraction was a primary factor in 28%. Fatigue was responsible for
      around one in 40 crashes and one in 12 fatal crashes. Alcohol or drugs was a
      factor in one in 12 crashes and one in nine fatal head-on crashes. Less than 8%
      of fatalities involved someone overtaking another vehicle, and only around 14%
      involved a driver intentionally crossing the centerline. Two in three fatal head
      on crashes occurred on straight segments and 67% of these happened on dry
      pavement. There is a clear trend towards higher speed limits leading to a higher
      percentage of crashes becoming fatal or having incapacitating injuries. There is
      also a clear trend - if one keeps speeds constant and AADT within a certain range
      - that wider shoulders give higher crash severities. Also, for higher-speed
      roads, more travel lanes (than two) increase crash severity. In summary, there
      seems to be two major reasons why people get across the centerline and have head
      on collisions: (a) people are going too fast for the roadway conditions; or (b)
      people are inattentive and get across the centerline more or less without
      noticing it. The latter category of crashes could probably be reduced if
      centerline rumble-strips were installed. More or less all head-on collisions
      could be eliminated if median barriers were installed. In-vehicle technology
      could also be used to significantly reduce the incidence of lane departures.
      Furthermore, today's speed limits should be better enforced since a high
      percentage of serious crashes involve illegal speeding. This should be combined
      with lowered speed limits for targeted high-crash segments.

PMID- 16423320
TI  - Automatic response activation of implicit spatial information: Evidence from the
      SNARC effect.
AB  - In the present paper, we focus on how irrelevant implicit spatial information is
      processed. By irrelevant we mean information that is not required to fulfill the
      task and by implicit we mean information that is not directly available in the
      external stimulus. A good example of a task in which such information exists is
      the SNARC task [Dehaene, S., Bossini, S., & Giraux, P. (1993). The mental
      representation of parity and number magnitude. Journal of Experimental
      Psychology: General, 122, 371-396]. The SNARC effect shows that the magnitude of
      a number, although irrelevant to the task, activates spatial codes that may
      interfere with the task-related response. These spatial associations exist both
      for the horizontal and the vertical direction. In Experiment 1, response keys
      were discriminating in the vertical or the horizontal direction. It is shown that
      the impact of the numerical spatial codes on overt behavior, although automatic,
      depends on the response discrimination of the horizontal or the vertical
      dimension. In Experiment 2, response keys were assigned such that both the
      horizontal and the vertical direction of the response were discriminating. In
      this case, the horizontal and the vertical dimension of the irrelevant numerical
      spatial codes were shown to interact. In general, the results are in line with
      the response-discrimination account [Ansorge, U., & Wuhr, P. (2004). A response
      discrimination account of the Simon effect. Journal of Experimental Psychology:
      Human Perception and Performance, 30, 365-377].

PMID- 16423321
TI  - Characterization of a nonspecific phosphopantetheinyl transferase from
      Pseudomonas syringae pv. syringae FF5.
AB  - The 4'-phosphopantetheinyl transferases (PPTases) catalyze the transfer of a 4'
      phosphopantetheine moiety from coenzyme A to phosphopantetheine-dependent carrier
      proteins. The carrier proteins (CPs) are required for the biosynthesis of
      peptides synthesized by nonribosomal peptide synthases and the biosynthesis of
      fatty acids and polyketides. A single PPTase (PcpS) is present in the pathogenic
      bacterium Pseudomonas aeruginosa. Several pathovars of Pseudomonas syringae
      produce the chlorosis-inducing phytotoxin coronatine. Structural genes for
      coronatine biosynthesis include two ACPs, two ACP domains, and one peptidyl
      carrier protein (PCP) domain. To gain insight into factors affecting coronatine
      biosynthesis, the PPTase of P. syringae pv. syringae FF5 has been investigated. A
      single PPTase gene (pspT) was amplified from this organism by PCR. The
      translation product PspT exhibited 62% identity to PcpS as well as higher levels
      of identity to other, uncharacterized Pseudomonad PPTases. PspT was overproduced
      in soluble form in Escherichia coli and its enzymatic properties were compared
      with those of PcpS. PspT exhibited broad substrate specificity, and it displayed
      the highest activity with a PCP domain. In contrast, the most efficient
      substrates for PcpS are CPs from primary metabolism. These results indicate
      phosphopantetheinyl transferases from different Pseudomonas sp. may vary
      significantly in their enzymatic properties.

PMID- 16423322
TI  - Evaluating anxiety sensitivity and other fundamental sensitivities predicting
      anxiety symptoms and fearful responding to a biological challenge.
AB  - Fear of arousal symptoms, often referred to as anxiety sensitivity (AS), appears
      to be associated with risk for anxiety pathology and other Axis I conditions.
      However, AS is only one of three fundamental components of Reiss' Expectancy
      Model proposed to account for the development of anxiety problems. Very little
      research has focused on the other two components of this model (Fear of Negative
      Evaluation, Illness/Injury Sensitivity) and the specificity of AS, relative to
      these other two components, has rarely been evaluated. This study evaluated
      general and unique associations among all three so-called fundamental
      sensitivities to fearful responding to a biological challenge in a nonclinical
      sample (N=404). Participants were administered a 20-s inhalation of 20%
      CO2/balance O2. Consistent with hypothesis, only AS uniquely contributed to
      increased subjective fear responding to the challenge. These findings are
      consistent with Expectancy Theory in suggesting that the AS component of the
      model is specific to amplification of fears to arousal cues.

PMID- 16423323
TI  - Comparison of test systems for RNAinterference.
AB  - RNAinterference (RNAi) has developed within a short time from an area of basic
      research occupied by a few experts to a widely used technical tool for reverse
      genetics, which is expected to have a broad utility not only in research, but
      also in medical and diagnostic applications. Despite its widespread use, the
      application of RNAi is often hampered because a difference of only a few
      nucleotides in the sequence of the target RNA can change the efficiency of a
      small interfering RNA (siRNA) from high to zero, and publicly available design
      tools for siRNAs are not yet perfect. We therefore developed and compared RNAi
      test systems based on different promoters, reporters, and target sequences. Here,
      we show that fluorescence-based test systems have obvious disadvantages compared
      to luciferase-based test systems and that some combinations of promoter,
      reporter, and target sequences, although currently in use, are not well suited
      for testing RNAi effects.

PMID- 16423324
TI  - Granulocyte colony-stimulating factor stimulates neurogenesis via vascular
      endothelial growth factor with STAT activation.
AB  - The adult brain harbors multipotent stem cells, which reside in specialized
      niches that support self-renewal. Granulocyte colony-stimulating factor (G-CSF)
      induces bone marrow stem cells proliferation and mobilization from their niche,
      and activates endothelial cell proliferation, which might help to establish a
      vascular niche for neural stem cells (NSCs). Here, we show that G-CSF induced
      receptor-mediated proliferation and differentiation of neural precursors in human
      NSCs cultures and in adult rat brain in vivo. In human NSCs cultures, G-CSF
      activated STAT3 and 5, and increased VEGF and its receptor, VEGFR2 (Flk-1)
      expression, and VEGFR2 tyrosine kinase inhibitor blocked the neurogenesis
      stimulated by G-CSF. G-CSF also activated endothelial cell proliferation in adult
      rat brain in vivo. Our results indicate that G-CSF stimulates neurogenesis
      through reciprocal interaction with VEGF and STAT activation.

PMID- 16423325
TI  - Hypothalamic monoamine metabolism is different between the diabetic GK (Goto
      Kakizaki) rats and streptozotocin-induced diabetic rats.
AB  - Hypothalamic neuronal activities of noradrenaline, dopamine and serotonin were
      investigated in the GK (Goto-Kakizaki) rats, a model for type 2 diabetes, and the
      streptozotocin (STZ)-induced diabetic rats, a model for type 1 diabetes. Each
      neuronal activity was assessed from a ratio of the concentrations of the major
      metabolite to those of its precursor monoamine itself or the metabolite
      concentrations itself. In the GK rats, hypothalamic noradrenaline and dopamine
      activities were significantly increased, and serotonin activity was unchanged. In
      the STZ-induced diabetic rats, hypothalamic dopamine and serotonin activities
      were significantly decreased, and noradrenaline activity was unchanged. In these
      two diabetic rats, hypothalamic noradrenaline and dopamine activities correlated
      significantly with serum insulin concentrations, whereas hypothalamic serotonin
      activity correlated significantly with serum glucose concentrations. These
      findings suggest that hypothalamic monoamine metabolism of the GK rats is quite
      different from that of the STZ-induced diabetic rats, and that not only
      hyperglycemia but also serum insulin concentrations have an influence on the
      hypothalamic monoamine metabolism in these diabetic rats.

PMID- 16423327
TI  - Distribution and expression of CRF receptor 1 and 2 mRNAs in the CRF over
      expressing mouse brain.
AB  - Corticotropin-releasing factor (CRF) acts through CRF 1 and CRF 2 receptors
      (CRF1, CRF2). To test the hypothesis that CRF controls the expression of these
      receptors in a brain site- and receptor-type specific manner, we studied CRF1
      mRNA and CRF2 mRNA expressions in mice with central CRF over-expression (CRF-OE)
      and using in situ hybridization. CRF1 and CRF2 mRNAs appear to be differentially
      distributed across the brain. The brain structures expressing the receptors are
      the same in wild-type (WT) and in CRF-OE mice. We therefore conclude that
      chronically elevated CRF does not induce or inhibit expression of these receptors
      in structures that normally do not or do, respectively, show these receptors.
      However, from counting cell body profiles positive for CRF1 and CRF2 mRNAs, clear
      differences appear in receptor expression between CRF-OE and WT mice, in a brain
      structure-specific fashion. Whereas some structures do not differ, CRF-OE mice
      exhibit remarkably lower numbers of CRF1 mRNA-positive profiles in the
      subthalamic nucleus (-38.6%), globus pallidus (-31.5%), dorsal part of the
      lateral septum (-23.5%), substantia nigra (-22,8%), primary somatosensory cortex
      (-18.9%) and principal sensory nucleus V (-18.4%). Furthermore, a higher number
      of CRF2 mRNA-positive profiles are observed in the dorsal raphe nucleus (+32.2%).
      These data strongly indicate that central CRF over-expression in the mouse brain
      is associated with down-regulation of CRF1 mRNA and up-regulation of CRF2 mRNA in
      a brain-structure-specific way. On the basis of these results and the fact that
      CRF-OE mice reveal a number of physiological and autonomic symptoms that may be
      related to chronic stress, we suggest that CRF1 in the basal nuclei may be
      involved in disturbed information processing and that CRF2 in the dorsal raphe
      nucleus may play a role in mediating stress-induced release of serotonin by CRF.

PMID- 16423326
TI  - 'Functional' neuroanatomical tract tracing: analysis of changes in gene
      expression of brain circuits of interest.
AB  - Neuroanatomical tracing when considered as an isolated method produces relatively
      straightforward answers. Although single-, double- or even triple-tracing
      paradigms produce valuable data on the organization of brain circuits, the final
      outcome often is too simplistic since it is not possible to elucidate the
      activity of these circuits. In this regard, emerging technologies contribute with
      additional information about the status of neuronal circuits. The laser-guided
      capture microdissection microscope (LCM) allows the accurate dissection of small
      brain areas under the microscope that could be further analyzed for gene
      expression or proteomics. In order to elucidate the gene expression of a given
      circuit of interest, we have developed a combination of methods comprising (i)
      fluorescent non-radioactive in situ hybridization for the detection of vGLUT2
      mRNA expression combined with retrograde tracing with Fluoro-Gold (FG; analysis
      performed under the confocal microscope) and (ii) laser-guided capture
      microdissection of brain areas containing neurons retrogradely labeled with FG
      followed by the measurement of changes in mRNA levels encoding for vGLUT2 by real
      time PCR. Our goal was to detect changes in gene expression of the
      thalamostriatal pathway in unilaterally 6-OHDA lesioned rats. Taking advantage of
      this procedure, we found a three-fold increase in vGLUT2 mRNA expression within
      thalamic neurons projecting to the dopamine-depleted striatum when compared with
      the activity of the thalamic neurons innervating the control striatum.

PMID- 16423328
TI  - Fluoxetine disrupts food intake and estrous cyclicity in Fischer female rats.
AB  - Adult, regularly cycling female Fischer rats were injected daily with 10 mg/kg
      fluoxetine for 12-23 days. In the first experiment, body weight and vaginal
      smears were monitored daily. Fluoxetine treatment reduced body weight within the
      first 24 h of treatment. Fluoxetine treatment also elongated the estrous cycle,
      reduced blood levels of progesterone, and eliminated lordosis behavior. In the
      second experiment, body weight and food intake were examined and a pair-fed group
      was included to determine if fluoxetine-induced anorexia contributed to the
      disturbance of the estrous cycle. In pair-fed rats, effects similar to fluoxetine
      treatment were present. These results lead to the suggestion that fluoxetine's
      anorectic properties could disrupt the female's normal endocrine cyclicity and
      that this disruption could be relevant to the reduction in sexual behavior and
      motivation. However, when the duration of fluoxetine treatment was extended
      beyond 16 to 17 days, fluoxetine-treated female rats reinitiated vaginal
      cyclicity and showed evidence of normal sexual receptivity. In contrast, the
      estrous cycles of their pair-fed counterparts remained disrupted. Thus,
      restricted food intake appears to contribute to the disruption of the estrous
      cycle and elimination of sexual receptivity during fluoxetine treatment. However,
      compensatory changes in the serotonergic system that are associated with chronic
      fluoxetine administration may contribute to the gradual recovery of estrous
      cyclicity and sexual receptivity of the fluoxetine-treated animals.

PMID- 16423329
TI  - Effects of nordihydroguaiaretic acid on Na+ currents in rat dorsal root ganglion
      neurons.
AB  - Nordihydroguaiaretic acid (NDGA) is a lipoxygenase (LO) inhibitor with a strong
      antioxidant activity. It attenuates nociceptive responses produced by various
      stimuli, which has been ascribed to its LO inhibition. Primary sensory neurons
      express multiple Na+ channels that are important in processing normal and
      abnormal nociception. We examined the effects of NDGA on tetrodotoxin-sensitive
      and tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurons. NDGA
      inhibited both types of Na+ currents concentration dependently and reversibly.
      Both activation and inactivation time courses were slowed by NDGA, which were not
      reversible. NDGA produced a hyperpolarizing shift of the steady-state
      inactivation curves and reduced the maximal availability of both Na+ currents,
      indicating that it blocks both inactivated and resting Na+ channels. NDGA shifted
      the conductance-voltage curves of both Na+ currents toward a depolarizing
      direction and increased the slope factors of the curves. The recovery of Na+
      channels from inactivation was retarded by NDGA. All these effects will reduce
      the excitability of sensory neurons and should be taken into account when it
      comes to the antinociceptive effects of NDGA.

PMID- 16423330
TI  - Catecholaminergic activation of G-protein coupling in rat spinal cord: further
      evidence for the existence of dopamine and noradrenaline receptors in spinal grey
      and white matter.
AB  - [35S]GTPgammaS autoradiography of slide-mounted tissue sections was used to
      examine G-protein coupling in the rat spinal cord, as stimulated by dopamine, the
      D1 receptor agonist SKF 38393, noradrenaline, and noradrenaline in the presence
      of the alpha adrenoceptor antagonist, phentolamine. Measurements were obtained
      from the different laminae of spinal grey and from the dorsal, lateral, and
      ventral columns of white matter, at cervical, thoracic, and lumbar levels. At
      every level, there was a relatively strong basal incorporation of GTPgammaS in
      laminae II-III>lamina IV-X of spinal grey, even in presence of DPCPX to block
      endogenous activation by adenosine A1 receptors. Dopamine, and to a lesser degree
      SKF 38393, but not the D2 receptor agonist quinpirole, stimulated G-protein
      coupling in laminae IV-X. Both dopamine and SKF 38393 also induced a weak but
      significant activation throughout the white matter. In both grey and white
      matter, the activation by dopamine was markedly reduced in presence of a
      selective D1 receptor antagonist. Noradrenaline strongly stimulated coupling
      throughout the spinal grey at all levels, an effect that was uniformly reduced in
      the presence of phentolamine. With or without phentolamine, there was also
      significant stimulation by noradrenaline in the white matter. Under the same
      experimental conditions, alpha 1, alpha 2, and beta adrenergic receptor agonists
      failed to activate GTPgammaS incorporation in either grey or white matter.
      However, in the presence of selective alpha 1 or alpha 2 receptor antagonist,
      significant reductions of noradrenaline-stimulated GTPgammaS incorporation were
      observed in both grey and white matter. The beta antagonist propanolol reduced
      GTPgammaS incorporation in grey matter only. Thus, the results confirmed the
      existence of D1 dopamine receptors and of alpha 1, alpha 2, and beta adrenergic
      receptors in the grey matter of rat spinal cord. In white matter, they strongly
      suggested the presence of dopamine D1, and of alpha 1 and alpha 2 adrenergic
      receptors on glia and/or microvessels, that might be activated by diffuse
      transmission in vivo.

PMID- 16423331
TI  - Effects of pharmacologically induced changes in NMDA receptor activity on human
      timing and sensorimotor performance.
AB  - Unlike processing of time intervals in the range of seconds or more, processing
      of brief durations in the subsecond range appears to be beyond cognitive control
      and based on subcortical mechanisms located in the basal ganglia. The present
      study was designed to evaluate the effects of NMDA receptor activity on temporal
      processing in the second and subsecond range. In a double-blind crossover design,
      either 30 mg of the noncompetitive NMDA receptor antagonist memantine or placebo
      was administered to 32 healthy male volunteers. While memantine induced a marked
      impairment in temporal processing of intervals in the range of seconds, temporal
      processing of intervals in the range of milliseconds was not affected.
      Furthermore, no effect of memantine on speed of information processing could be
      observed. Speed of motor response execution, however, was significantly enhanced
      by memantine compared to placebo. The overall pattern of results provides
      converging evidence for the notion that temporal processing of longer intervals
      involves higher order working memory functions such as working memory capacity.
      The absence of an effect on temporal processing of very brief intervals in
      combination with the beneficial effect on movement time suggests that NMDA
      receptor activity in the basal ganglia is not directly related to the timing of
      intervals in the subsecond range.

PMID- 16423332
TI  - Cognitive disturbances in old dogs suffering from the canine counterpart of
      Alzheimer's disease.
AB  - In geriatric dogs, Alzheimer-like behavior is frequently observed. This behavior
      has been classified by several authors using questionnaires and a correlation has
      been described between cognitive dysfunctions and Alzheimer-like pathology. In
      the present study, cognitive performance was correlated with brain pathology for
      30 dogs of varying ages. Within these animals, two age-matched groups of old dogs
      with and without behavioral changes were compared. The behavioral changes were
      analyzed and scored with questionnaires and necropsy was performed to rule out
      any other cause for changed behavior. Measurements, (immuno)-histochemical
      staining and fluorescence microscopy were used to detect cortex atrophy, amyloid,
      rest-products of oxidative damage, demyelination and accumulations of macrophages
      in the brains of these dogs. Spearman rank correlation coefficients (r) were
      calculated and adjusted according to Bonferonni. In the whole group (young to
      very old dogs), the age of the animal showed a significant correlation with
      various behavioral changes (r = 0.7 to 0.9, P < 0.01). The dementia score
      correlated significantly (r = 0.6 to 0.8, P < 0.01) with all the brain lesions
      studied, except one, i.e. demyelination (r = -0.4, P > 0.05). These results
      suggest that a questionnaire can be used to diagnose Alzheimer-like changes in
      canine practice. Oxidative damage on a cellular and a nuclear level plays an
      important role in behavior changes.

PMID- 16423334
TI  - Alterations in BDNF and trkB mRNAs following acute or sensitizing cocaine
      treatments and withdrawal.
AB  - In the present study, we used in situ hybridization to examine the influence of
      acute or repeated cocaine administrations and withdrawal from repeated cocaine
      treatment on the level of brain-derived neurotrophic factor (BDNF) and its
      receptor trkB mRNAs in rat brain. Cocaine (10 mg/kg i.p.) injected acutely
      produced locomotor hyperactivation, while repeated (single injection for 5 days)
      administrations of cocaine (10 mg/kg) induced a two-fold increases in the
      locomotor activity in rats in response to a challenge cocaine dose (10 mg/kg) on
      day 10, as compared to the saline-treated animals (sensitization). Cocaine
      treatments induced a brain-region-specific decrease in the levels of trkB mRNA.
      On the other hand, BDNF mRNA in the rat hippocampus was increased only in the
      group of rats subjected to cocaine withdrawal. Animals under cocaine withdrawal
      demonstrated a significant increase in the immobility time measured by the use of
      modified forced swimming test. Therefore, the increases in the levels of BDNF
      mRNA in the rat hippocampus seem to be correlated with "depressive-like"
      behavioral effects during withdrawal from repeated cocaine treatment. In the
      shell (but not in the core) of the nucleus accumbens, the levels of BDNF mRNA
      were significantly increased following acute and repeated cocaine treatment as
      well as during cocaine withdrawal, which indicates that the alterations in the
      neurotrophin level in the brain region important for the expression of cocaine
      induced sensitization involve other mechanisms.

PMID- 16423333
TI  - Long-term expression of corticotropin-releasing factor (CRF) in the
      paraventricular nucleus of the hypothalamus in response to an acute colonic
      inflammation.
AB  - This study examined the long-term effects of an acute colitis on central
      corticotropin-releasing factor (CRF) expression. An increase in CRF mRNA in the
      paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the
      amygdala (CeA) was observed during active colitis, and the effect in the PVN was
      maintained following recovery. In summary, hypothalamic gene expression of CRF
      persists in the PVN despite resolution of an acute colitis.

PMID- 16423336
TI  - Analytical validation of an HPLC assay for urinary albumin.
AB  - BACKGROUND: Microalbuminuria is the earliest clinical finding for renal disease.
      Diabetic individuals often produce modified forms of albumin, perhaps due to
      impaired lysosomal processing, that are undetectable by common immunoassays but
      accurately measured by HPLC. METHODS: We evaluated the performance of a
      commercially available, FDA-approved HPLC assay (AusAm Biotechnologies, NY) and
      compare results to our immunoturbidimetric assay (ITA, Beckman-Coulter, CA) using
      random urine specimens from 32 nondiabetic and 60 type 1 and 2 diabetic subjects.
      RESULTS: The HPLC assay was linear to 963 mg/l with a limit of detection of 6.1
      mg/l. Within-run and between-run precision was <2% and 7-10%, respectively.
      Unpreserved urine was stable for at least 3 days at room temperature and 10 days
      at 4 degrees C. In both diabetic and nondiabetic subjects urinary albumin
      concentrations were higher by HPLC than by ITA, and many more diabetic and
      nondiabetic individuals were classified as microalbuminuric by HPLC than by ITA.
      The HPLC assay showed acceptable performance; however, because urinary albumin
      concentrations are higher in apparently healthy nondiabetic as well as diabetic
      subjects, different cutpoints will be necessary to accurately differentiate
      microalbuminuria. CONCLUSIONS: Prospective studies are necessary to determine
      whether the HPLC assay can effectively detect microalbuminuria earlier than
      current assays without a concomitant increase in the false positive rate.

PMID- 16423335
TI  - Urinary biomarkers of 1,3-butadiene in environmental settings using liquid
      chromatography isotope dilution tandem mass spectrometry.
AB  - Although, 1,3-butadiene is a known human carcinogen emitted from mobile sources,
      little is known about traffic-related human exposure to this toxicant. This pilot
      study was designed to characterize traffic-related environmental exposure to 1,3
      butadiene and evaluate its urinary mercapturic acids as biomarkers of exposure in
      these settings. Personal air samples and multiple urine samples were collected on
      two separate occasions from three groups of individuals that differed by spatial
      proximity as well as intensity of traffic: (i) toll collectors, (ii) urban
      weekday and (iii) suburban-weekend group. Air samples were analyzed using thermal
      desorption followed by GC/MS and urine samples were analyzed using isotope
      dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) for two
      mercapturic acids of 1,3-butadiene: monohydroxy-3-butenyl mercapturic acid
      (MHBMA) and 1,2-dihydroxybutyl mercapturic acid (DHBMA). Exposure differed
      between groups (p<0.05) with median values of 2.38, 1.62 and 0.88 microg/m(3) for
      toll collectors, the urban-weekday group and the suburban-weekend group,
      respectively. A refined ID-LC-MS/MS method enabled detection of MHBMA, previously
      detected only in occupational settings, with high frequency. MHBMA and DHBMA were
      detected in 95 and 100% of urine samples at levels (mean+/-S.D.) of 9.7+/-9.5,
      6.0+/-4.3 and 6.8+/-2.6 ng/mL for MHBMA and 378+/-196, 258+/-133 and 306+/-242
      ng/mL for DHBMA for the three different groups, respectively. Mean biomarker
      levels were higher among the toll collectors compared to the other two groups,
      however, the differences were not statistically significant (p>0.05). This study
      is the first to evaluate 1,3-butadiene biomarkers for subtle differences in
      environmental exposures. However, additional research will be required to
      ascertain whether the lack of statistical association observed here is real or
      attributable to unexpectedly small differences in exposure between groups (<1
      microg/m(3)), non-specificity of the biomarker at low exposure, and/or small
      sample size.

PMID- 16423337
TI  - Pediatric reference intervals for bone markers.
AB  - Bone markers are specific bone-derived molecules that reflect bone remodeling
      activity and can be classified into two categories: bone formation and bone
      resorption markers. Children have significantly elevated bone marker levels due
      to high skeletal growth velocity and rapid bone turnover during childhood growth.
      Many physiological and pathological processes may influence bone metabolism and
      bone marker concentrations during childhood growth. Measurements of bone markers
      may be useful in investigating skeletal diseases in children and monitoring the
      response to treatment. This review documents recent advances in analytical
      methods, preanalytical considerations related to each marker and particularly
      highlights the most valuable bone formation markers, bone alkaline phosphatase
      and osteocalcin, and bone resorption markers, pyridinium cross-links and cross
      linked telopeptides. Age- and sex-specific pediatric reference intervals and
      their limitations in clinical application are also discussed.

PMID- 16423338
TI  - Association of the IL-1RN2 allele with periodontal diseases.
AB  - OBJECTIVES: Interleukin-1 receptor antagonist (IL-1Ra) gene (IL-1RN) polymorphism
      is associated with disease susceptibility and activity in several inflammatory
      diseases. The aim of this study was to investigate IL-1RN genotype and its
      associations with different periodontal diseases in a group of Turkish subjects.
      DESIGN AND METHODS: A total of 293 subjects were included in this study. Genomic
      DNA was obtained from the peripheral blood of 52 patients with generalized
      aggressive periodontitis (G-AgP), 51 with chronic periodontitis (CP) and 190
      reference subjects. A variable number tandem repeat (VNTR) polymorphism in the
      second intron of the IL-1RN gene was detected by PCR-based methods. Probing
      pocket depth, clinical attachment loss, plaque accumulation and bleeding on
      probing (BOP) were recorded. The data were analyzed by the chi(2) test, logistic
      regression and Mann-Whitney U test. RESULTS: There were significant differences
      among the groups in the distribution of IL-1RN genotypes (P = 0.0001) and allele
      frequencies (P = 0.0001). The frequency of IL-1RN2 allele 2 positivity was higher
      in the AgP and CP group than the reference group [odds ratio (OR) 6.654, 95% CI:
      3.023-16.648; OR 10.327, 95% CI: 4.758-22.412, respectively]. The percentage of
      sites with BOP was significantly higher in IL-1RN2+ compared to IL-1RN2- CP
      patients (P = 0.022). CONCLUSION: These results suggest that IL-1RN2 allele
      positivity is associated with periodontal disease in a Turkish population.

PMID- 16423339
TI  - Serum ribonuclease activity in the diagnosis of prostate cancer in men with serum
      prostate-specific antigen levels between 2.5 and 20 ng/mL.
AB  - OBJECTIVES: To evaluate the diagnostic value of serum ribonuclease activity for
      prostate cancer detection and to compare its performance with serum PSA. DESIGN
      AND METHODS: 111 subjects with serum PSA levels between 2.5 and 20 ng/mL
      underwent prostate biopsy. The diagnostic performance of serum ribonuclease
      activity, PSA, free PSA, complex PSA and PSA derivatives was studied in regard to
      discriminating prostate cancer from BPH. RESULTS: Of 111 patients, 27 (24.3%)
      were positive for prostate cancer. Median serum ribonuclease level in patients
      with prostate cancer was significantly higher than the non-cancer patients (21.3
      U/mL vs. 6.6 U/mL, P < 0.001). Area under curve (AUC) values for ribonuclease
      activity level, PSA, f/tPSA and cPSA were 0.696, 0.514, 0.617 and 0.662,
      respectively. Of 27 patients with prostate cancer, radical prostatectomy was
      performed in 15. Of these 15 cases, four (26.7%) had clinical insignificant
      tumors; all with undetectable serum ribonuclease activity. When median values of
      various diagnostic parameters were compared in regard to predicting clinically
      significant and insignificant cancers, only serum ribonuclease activity was found
      to be significant. CONCLUSIONS: Although serum ribonuclease activity had no
      additional benefit beyond serum PSA in the diagnosis of patients with PSA levels
      between 2.5 and 20 ng/mL, it may be helpful to discriminate the clinically
      significant prostate cancers and thus select the proper treatment accordingly.

PMID- 16423340
TI  - Functional polymorphism in the manganese superoxide dismutase (MnSOD) gene in
      patients with asthma.
AB  - OBJECTIVES: To investigate the possible association between functional variant
      Ala-9Val in the MnSOD gene and asthma in the case-control study comprising 626
      Caucasian subjects. METHODS: MnSOD genotypes were determined by PCR with
      subsequent restriction analysis by the BsaWI enzyme. RESULTS: Significant
      differences in allele frequencies between groups were not ascertained.
      CONCLUSIONS: Pursuant to these results, Ala-9Val polymorphism does not seem to be
      a significant predisposing factor for bronchial asthma in the Czech population.

PMID- 16423342
TI  - scylla and charybde, homologues of the human apoptotic gene RTP801, are required
      for head involution in Drosophila.
AB  - We employed robotic methods and the whole-genome sequence of Drosophila
      melanogaster to facilitate a large-scale expression screen for spatially
      restricted transcripts in Drosophila embryos. In this screen, we identified a
      pair of genes, scylla (scyl) and charybde (chrb), that code for dorsal
      transcripts in early Drosophila embryos and are homologous to the human apoptotic
      gene RTP801. In Drosophila, both gene products are transcriptionally regulated
      targets of Dpp/Zen-mediated signal transduction and appear more generally to be
      downstream targets of homeobox regulation. Gene disruption studies revealed the
      functional redundancy of scyl and chrb, as well as their requirement for
      embryonic head involution. From the perspective of functional genomics, our
      studies demonstrate that global surveys of gene expression can complement
      traditional genetic screening methods for the identification of genes essential
      for development: beginning from their spatio-temporal expression profiles and
      extending to their downstream placement relative to dpp and zen, our studies
      reveal roles for the scyl and chrb gene products as links between patterning and
      cell death.

PMID- 16423341
TI  - Retinoic acid signaling is essential for formation of the heart tube in Xenopus.
AB  - Retinoic acid is clearly important for the development of the heart. In this
      paper, we provide evidence that retinoic acid is essential for multiple aspects
      of cardiogenesis in Xenopus by examining embryos that have been exposed to
      retinoic acid receptor antagonists. Early in cardiogenesis, retinoic acid alters
      the expression of key genes in the lateral plate mesoderm including Nkx2.5 and
      HAND1, indicating that early patterning of the lateral plate mesoderm is, in
      part, controlled by retinoic acid. We found that, in Xenopus, the transition of
      the heart from a sheet of cells to a tube required retinoic acid signaling. The
      requirement for retinoic acid signaling was determined to take place during a
      narrow window of time between embryonic stages 14 and 18, well before heart tube
      closure. At the highest doses used, the lateral fields of myocardium fail to
      fuse, intermediate doses lead to a fusion of the two sides but failure to form a
      tube, and embryos exposed to lower concentrations of antagonist form a heart tube
      that failed to complete all the landmark changes that characterize looping. The
      myocardial phenotypes observed when exposed to the retinoic acid antagonist
      resemble the myocardium from earlier stages of cardiogenesis, although precocious
      expression of cardiac differentiation markers was not seen. The morphology of
      individual cells within the myocardium appeared immature, closely resembling the
      shape and size of cells at earlier stages of development. However, the failures
      in morphogenesis are not merely a slowing of development because, even when
      allowed to develop through stage 40, the heart tubes did not close when embryos
      were exposed to high levels of antagonist. Indeed, some aspects of left-right
      asymmetry also remained even in hearts that never formed a tube. These results
      demonstrate that components of the retinoic acid signaling pathway are necessary
      for the progression of cardiac morphogenesis in Xenopus.

PMID- 16423344
TI  - [35S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4
      and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine.
AB  - Aim of the present study was to investigate possible differences between the
      human dopamine D4 receptor 48 bp polymorphism variants hD4.2, hD.4. and hD4.7 in
      agonist stimulated [35S]GTPgammaS binding, to investigate dopamine D4 receptor
      sodium sensitivity and to further characterize norepinephrine and epinephrine
      agonism at this receptor. G-protein activation at the receptor variants hD4.2,
      hD4.4 and hD4.7 expressed in CHO-K1 cells, following stimulation by dopamine,
      norepinephrine and epinephrine, was investigated using the [35S]GTPgammaS assay
      at experimental conditions of 10 and 100 mM sodium, respectively. Dopamine
      displayed a 2 fold higher potency of stimulating [35S]GTPgammaS binding at the
      hD4.2, compared to the hD4.4 and hD4.7 at 10 mM sodium. A significant difference
      in sodium sensitivity of basal [35S]GTPgammaS binding was found, with the hD4.7
      being 1.7 fold more sensitive than the hD4.4 and 2.5 fold more sensitive than the
      hD4.2. Norepinephrine and epinephrine both produced concentration-dependent
      increases in [35S]GTPgammaS binding at all three receptor variants, and
      epinephrine showed only 2 fold less potency than dopamine. The present results
      are in certain line with previous reports of functional 2-3 fold differences
      between the dopamine D4 receptor variants. Agonism of norepinephrine and
      epinephrine at the dopamine D4 receptor may indicate an important way of cross
      reactivity among the different monoamine neurotransmitter systems.

PMID- 16423343
TI  - The mouse Ovol2 gene is required for cranial neural tube development.
AB  - The Ovo gene family encodes a group of evolutionarily conserved transcription
      factors and includes members that reside downstream of key developmental
      signaling pathways such as Wg/Wnt and BMP/TGF-beta. In the current study, we
      explore the function of Ovol2, one of three Ovo paralogues in mice. We report
      that Ovol2 is expressed during early-mid embryogenesis, particularly in the inner
      cell mass at E3.5, in epiblast at E6.5, and at later stages in ectodermally
      derived tissues such as the rostral surface (epidermal) ectoderm. Embryos in
      which Ovol2 is ablated exhibit lethality by E10.5, prior to which they display
      severe defects including an open cranial neural tube. The neural defects are
      associated with improper Shh expression in the underlying rostral axial mesoderm
      and localized changes of neural marker expression along the dorsoventral axis, as
      well as with expanded cranial neural tissue and reduced cranial surface ectoderm
      culminating in a lateral shift of the neuroectoderm/surface ectoderm border. We
      propose that these defects reflect the involvement of Ovol2 in independent
      processes such as regionalized gene expression and neural/non-neural ectodermal
      patterning. Additionally, we present evidence that Ovol2 is required for
      efficient migration and survival of neural crest cells that arise at the
      neuroectoderm/surface ectoderm border, but not for their initial formation.
      Collectively, our studies indicate that Ovol2 is a key regulator of neural
      development and reveal a previously unexplored role for Ovo genes in mammalian
      embryogenesis.

PMID- 16423345
TI  - Inhibition of cardiac HERG potassium channels by antidepressant maprotiline.
AB  - Many drugs block delayed rectifier K+ channels and prolong the cardiac action
      potential duration. Here we investigate the molecular mechanisms of voltage
      dependent block of human ether-a-go-go-related gene (HERG) K+ channels expressed
      in cells HEK-293 and Xenopus oocytes by maprotiline. The IC50 determined at 0 mV
      on HERG expressed HEK-293 cell and oocytes was 5.2 and 23.7 microM, respectively.
      Block of HERG expressed in oocytes by maprotiline was enhanced by progressive
      membrane depolarization and accompanied by a negative shift in the voltage
      dependence of channel activation. The potency of maprotiline was reduced 7-fold
      by point mutation of a key aromatic residue (F656T) and 3-fold for Y652A, both
      located in the S6 domain. The mutation Y652A inverted the voltage dependence of
      HERG channel block by maprotiline. Together, these results suggest that voltage
      dependent block of HERG results from gating dependent changes in the
      accessibility of Y652, a critical component of the drug binding site.

PMID- 16423346
TI  - Prenatal exposure to a cannabinoid receptor agonist does not affect sensorimotor
      gating in rats.
AB  - Clinical evidence suggests that prenatal exposure to cannabis may be conducive to
      long-term neurobehavioral impairments in executive and attentional domains. Such
      sensorimotor alterations might be related to disorders in gating functions.
      Hence, the present study was undertaken to assess the effects of long-term
      prenatal exposure to WIN 55,212-2, a potent cannabinoid receptor agonist, on
      prepulse inhibition of the acoustic startle reflex, a well-validated paradigm to
      test sensorimotor gating. In utero exposure to WIN 55,212-2 (0.5, 1 mg/kg, from
      day 5 to 20 of gestation) failed to alter startle magnitude in rats in comparison
      with controls. Similarly, prepulse inhibition of the startle was not
      significantly affected by such treatment, regardless of the age when behavioral
      testing was carried out (40, 60 or 80 days). Interestingly, prenatal treatment
      with WIN 55,212-2 (0.5 mg/kg, from day 5 to 20 of gestation) induced no
      differences in the prepulse inhibition-disrupting effects of apomorphine (0.125,
      0.25 mg/kg, s.c.) and dizocilpine (0.05, 0.1 mg/kg, s.c.), suggesting that a
      prenatal exposure to a cannabinoid receptor agonist is likely unable to affect
      sensitivity of sensorimotor gating substrates to dopaminergic agonists and NMDA
      receptor antagonists. Our results show that prenatal exposure to cannabis does
      not affect reflex reactivity to environmental stimuli, ruling out that the
      observed impairments in executive functions are to refer to sensorimotor gating
      alterations.

PMID- 16423347
TI  - Activation of cannabinoid CB1 receptors induces glucose intolerance in rats.
AB  - Recent reports have described the presence of cannabinoid CB1 receptors in
      pancreatic islets. Here we show that administration of the endogenous cannabinoid
      anandamide or the selective cannabinoid CB1 receptor agonist Arachidonyl-2'
      chloroethylamide (ACEA) results in glucose intolerance after a glucose load. This
      effect is reversed by the selective cannabinoid CB1 receptor antagonist N
      (piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide (AM251). These results suggest that targeting cannabinoid CB1
      receptors may serve as new therapeutic alternatives for metabolic disorders such
      as diabetes.

PMID- 16423348
TI  - Amelioration of autoimmune neuroinflammation by recombinant human alpha
      fetoprotein.
AB  - Alpha-fetoprotein (AFP) is a 65-kDa oncofetal glycoprotein found in fetal and
      maternal fluids during pregnancy. Clinical remissions during pregnancy have been
      observed in several autoimmune diseases, such as multiple sclerosis (MS), and
      have been attributed to the presence of pregnancy-associated natural immune
      reactive substances, including AFP which can exert immunomodulatory effects on
      immune cells. In this study, we tested the effect of recombinant human AFP
      (rhAFP) isolated from transgenic goats, which contain the genomic DNA for hAFP,
      on experimental autoimmune encephalomyelitis (EAE), the animal model used for the
      study of MS. RhAFP treatment markedly improved the clinical manifestations of
      EAE, preventing central nervous system (CNS) inflammation and axonal
      degeneration. RhAFP exerted a broad immunomodulating activity, influencing the
      various populations of immune cells. T cells from treated mice had significantly
      reduced activity towards the encephalitogenic peptide of myelin oligodendrocyte
      glycoprotein (MOG), exhibiting less proliferation and reduced Th1 cytokine
      secretion. Moreover, AFP affected the humoral response, causing an inhibition in
      MOG-specific antibody production. The expression of CD11b, MHC class II and the
      chemokine receptor CCR5 was also down-regulated. This is the first study
      demonstrating reduced inflammation and axonal damage exerted by recombinant AFP.
      In light of our findings, rhAFP may serve as a potential candidate for treatment
      of MS and other autoimmune diseases.

PMID- 16423349
TI  - Perimicrovascular edema in the frontal cortex in a rat model of intraperitoneal
      sepsis.
AB  - Septic encephalopathy is a complication of sepsis, and it is closely associated
      with the increased mortality of the sufferers. Pathophysiology of septic
      encephalopathy is not still completely understood. In an attempt to provide
      insight into the pathogenesis of septic encephalopathy, a light and electron
      microscopic investigation has been carried out in a rat model of intraperitoneal
      sepsis. Experimental fecal peritonitis was induced in Wistar rats which have been
      monitored for 6 h and sacrificed to harvest the samples of frontal cortex. Vital
      parameters and morphometric data obtained from investigation of the microvessels
      were then compared with the sham-operated and unoperated controls. In addition to
      the discernible drop in the blood pressure and in rectal temperature following
      initial increases, unstable but usually increased heart rate and marked
      respiratory failure were recorded. Estimation of the percentage of the
      microvessel area occupied by edema revealed the presence of significantly more
      perimicrovascular edema in the experimental fecal peritonitis group compared to
      both sham-operated and unoperated controls, while no significant difference was
      present between the latter two groups. Electron microscopic investigation
      confirmed the presence of distinctive perimicrovascular edema in the fecal
      peritonitis group although the endothelial cells were linked by tight junctions
      which appeared morphologically intact. Although it might be premature to draw any
      strict parallels between the septic encephalopathy in humans and the findings
      observed in the present model, the results may suggest that the edema observed
      around the microvessels would bare a role in the pathogenesis of the septic
      encephalopathy probably by affecting the exchange of oxygen and nutrients with
      carbon dioxide and waste products between the blood and brain parenchyma.

PMID- 16423350
TI  - Dynamic analysis of a genomic island in Magnetospirillum sp. strain AMB-1 reveals
      how magnetosome synthesis developed.
AB  - The entire structure of a 98 kb genomic region that abounds in genes related to
      magnetosome synthesis was first described in the Magnetospirillum sp. strain AMB
      1. The deletion of this 98 kb genomic region and the circular form after excision
      from the chromosome was detected by PCR amplification. This strongly suggests
      that the region has undergone a lateral gene transfer. The region has the
      characteristics of a genomic island: low GC content, location between two
      repetitive sequences, and the presence of an integrase in the flanking region of
      the first repetitive sequence. This 98 kb genomic region has the potential for
      transfer by the integrase activity. Comparative genome analysis revealed other
      regions with a high concentration of orthologs in magnetic bacteria besides the
      98 kb region, and magnetosome synthesis seemed to need not only the exogenous 98
      kb region, but also other orthologs and individually originating genes.

PMID- 16423351
TI  - Kidney function and the role of arginine vasotocin in three agamid lizards from
      habitats of differing aridity in Western Australia.
AB  - Western Australian agamid lizards are diverse and inhabit mesic to very arid
      areas of the state. Although reptilian kidneys are unable to elaborate
      hyperosmotic urine, we hypothesised that the renal system of lizards inhabiting
      arid areas would display an enhanced ability to conserve water under the control
      of the antidiuretic peptide hormone, arginine vasotocin (AVT). To examine this,
      the renal physiological and endocrine responses to osmotic challenge in three
      closely-related Australian agamid lizards inhabiting arid, semi-arid, and mesic
      environments were studied. The species studied were Pogona minor (mesic),
      Ctenophorus salinarum (semi-arid), and Ctenophorus nuchalis (arid). Circulating
      AVT was assayed and renal variables such as glomerular filtration rate (GFR),
      urine flow rate (V), and fractional reabsorption of filtrate FRH2O were measured
      in response to hypernatraemia, water load, and dehydration. Hypernatraemia and
      dehydration induced antidiuresis in all three species through similar mechanisms
      involving both glomerular and tubular responses. However, in salt-loaded P. minor
      the response was largely glomerular in nature, as FRH2O did not increase relative
      to the hydrated condition. The magnitude of the antidiuretic response was also
      greater in P. minor, indicating a greater sensitivity to osmotic challenge.
      Plasma concentrations of AVT were significantly correlated with FRH2O in P. minor
      (r2=0.38, P=0.025), but with GFR in C. nuchalis (r2=0.16, P=0.041). We found that
      the control and mechanisms of renal function among these lizards were largely
      similar, and there was little support for the hypothesis that arid lizards
      possess physiological adaptations not present in closely-related mesic lizards.
      Yet, differences remain in their response to hypernatraemia which may reflect the
      aridity of their different environments, or their varying habits.

PMID- 16423352
TI  - Chronic disruption of body weight but not of stress peptides or receptors in rats
      exposed to repeated restraint stress.
AB  - Rats exposed to restraint stress for 3 h on each of 3 days lose weight and do not
      return to the weight of their non-stressed controls for extended periods of time.
      Studies described here demonstrate that the initial weight loss is associated
      with increased energy expenditure and reduced food intake on the days of
      restraint but that there is no difference between stressed and control rats once
      stress ends. The failure to compensate for this energy deficit accounts for the
      sustained reduction in weight which lasts for up to 80 days after the end of
      restraint. In an additional experiment, in situ hybridization was used to measure
      mRNA expression of corticotrophin releasing factor (CRF) and CRF receptors in
      hypothalamic nuclei, of urocortin (UCN) in the Edinger Westphal nucleus and of
      UCN III in the rostral perifornical area and medial amygdaloidal nucleus.
      Immediately after the second 3 h bout of restraint stress, there was a
      significant increase in expression of UCN in the Edinger Westphal nucleus and of
      CRF-R1 in the paraventricular nucleus of the hypothalamus and a less pronounced
      decrease in CRF-R2 expression in the ventromedial nucleus of the hypothalamus.
      There were no differences in expression of stress-related peptides or their
      receptors 40 days after the end of repeated restraint. These results suggest that
      the sustained reduction in body weight and increased responsiveness to subsequent
      stressors in rats that have been exposed to repeated restraint are not associated
      with prolonged changes in mRNA expression of CRF receptors or their ligands.

PMID- 16423353
TI  - Sex hormones, central nervous system and pain.
AB  - The aim of the present review, which highlights some relationships between sex
      hormones, the CNS and pain, is to provide reference points for discussion on one
      of the most intriguing aspects of pain pathophysiology: the presence of sex
      differences in the response threshold to phasic painful stimuli and in the
      incidence of chronic pain syndromes. The first part of the review deals with sex
      steroids and their mechanisms of action. In the second part, the connections
      between sex steroids, the CNS and pain are illustrated to introduce possible
      areas of discussion in the study of sex differences in experimental and clinical
      pain.

PMID- 16423354
TI  - Developing a managed clinical network in palliative care: a realistic evaluation.
AB  - BACKGROUND: The attainment of evidence-based practice is at the fore of the
      international practice development agenda. It is therefore imperative that robust
      evaluation methodologies are available to scrutinise new approaches to service
      development. OBJECTIVES: This paper reflects on the merits and challenges of
      realistic evaluation design in the establishment of a new managed clinical
      network (MCN) approach to implementing a guideline concerned with the care of
      individuals with cancer-related pain. DESIGN AND METHODS: There were three
      evaluation points scrutinising three versions of the MCN approach to care. At
      each stage, steps were taken to identify the context, mechanisms and outcomes
      associated with the version of the model under scrutiny. Findings from patient
      centred case studies fed into realistic evaluation interviews with the management
      group. SETTING: A rural primary care setting in Scotland. PARTICIPANTS: Three
      older men, their families, and the doctors and nurses providing direct care
      participated, along with 13 members of the network management group. RESULTS: The
      investigation highlighted the level of practitioner effort required to introduce
      the MCN approach to care. Progress was much slower than anticipated, at times
      frustrated by inexperience in change management and unfamiliarity with leading
      practice development projects and supporting practitioner learning. Issues to do
      with the age appropriateness of the evidence base in relation to the care of
      frail older people were also apparent. The professional group that experienced
      most role change were district nurses and community pharmacists. CONCLUSION: The
      collaborative approach nurtured by the realistic evaluation framework was found
      particularly helpful and there was consensus that the evaluation had become
      integral to the intervention itself. There were a number of methodological
      challenges and a need to limit the depth of 'realistic unravelling'. However, as
      a formative approach, in the messy world of interdisciplinary practice
      development, realistic evaluation proved a worthy design.

PMID- 16423355
TI  - Do public access defibrillation (PAD) programmes lead to an increase of patients
      surviving to discharge from hospital following out of hospital cardiac arrest?--a
      literature review.
AB  - OBJECTIVE: To ascertain the evidence for effectiveness of Public Access
      Defibrillation Programmes using any level of first responder. DATA SOURCES:
      Structured searches were made of Medline, Cinahl, Embase, and 'All EBM reviews'
      (CDSR, ACP Journal Club, DARE, CCTR). No limits were set on the searches in terms
      of date, publication type or language. Limited hand searches were carried out and
      colleagues approached for potential papers. REVIEW METHODS: All 491 results were
      'hand searched' for suitability. Potential papers for inclusion were further
      reviewed by access to abstracts or full text if necessary. The final papers for
      review were assessed using a recognised checklist. RESULTS: Of a total of 491
      results from all databases removal of repeats and papers that did not answer the
      question led to 22 papers being further reviewed. Of these 19 were excluded and a
      final three were assessed and reviewed. Of the three papers two were randomised
      controlled trials (one with cross over design) and one was a non-randomised
      controlled cross over trial. Two of the papers assessed the use of level one
      responders and one level two responders. Odds ratios for the trials using level
      one responders were 1.3 and 1.6. The relative risk (of survival) for the trial
      using level two responders was 2.0. However all three trials had wide confidence
      intervals. CONCLUSION: The use of level one responders probably carries a slight
      benefit for patients in OOHCA. The use of level two responders may lead to a
      greater benefit but only for a small section of the population suffering OOHCA.
      Emphasis must also be placed on the improvement of ambulance response times and
      bystander CPR rates.

PMID- 16423356
TI  - Overexpression of human ApoAI transgene provides long-term atheroprotection in
      LDL receptor-deficient mice.
AB  - The long-term effect of elevated levels of human apolipoprotein AI (apoAI) on
      atherosclerosis was assessed using human apoAI transgenic mice on a double mutant
      LDL receptor-deficient (LDLr-/-) and mouse apoAI-deficient (apoAI-/-) background.
      When they were fed a high fat diet, atherosclerosis in transgenic human apoAI,
      LDLr-/-, apoAI-/- mice (huapoAITg) was compared with LDLr-/- mice that expressed
      normal amounts of apoAI (msapoAI) or LDLr-/- mice that lacked mouse apoAI
      (noapoAI). The atheroprotective effect of human apoAI was demonstrated by a
      greater than six-fold inhibition in lesion areas in the aortic wall and heart
      valves compared to the two control strains after 27 or 36 weeks. Plasma apoAI
      concentrations in huapoAITg mice were considerably higher than in msapoAI mice
      (600 and 37 mg/dL, respectively). The human apoAI transgene led to several plasma
      HDL subpopulations, with high levels of prebeta-HDL and a significant decrease in
      total plasma cholesterol. This was observed without a change in total HDL
      cholesterol levels. Thus, elevated levels of human apoAI in LDL receptor
      deficient mice lacking mouse apoAI conferred profound protection against diet
      induced over extended periods of time.

PMID- 16423357
TI  - Influence of bicycle seat pressure on compression of the perineum: a MRI
      analysis.
AB  - It is a common belief that bicycle seat pressure compresses neurovascular tissues
      in the perineum and may lead to perineal and penile pathologies in male cyclists.
      The purpose of this study was to examine the effect bicycle seat pressure has on
      compression of the perineal cavernous spaces, which house the penile
      neurovascular tissues. A second purpose was to identify where peak cavernous
      compression occurs in relation to a bicycle seat. Five males were assessed for
      compression of the corpus spongiosum and corpora cavernosa with and without
      bicycle seat pressure using MRI. Seat pressure was applied using a custom loading
      device designed to replicate seat pressure recorded during stationary bicycling.
      The distance between a horizontal midline of the seat and the point of peak
      cavernous space compression was made on sagittal plane images. Diameter
      measurements of the cavernous spaces at the point of peak compression were made
      on coronal plane images. Results revealed that peak cavernous space compression
      occurred below the pubic symphysis, 40.7(+/-11.4) mm anterior to the midline of
      the seat. Corpus spongiosum values in the unloaded condition were 148% greater
      than the loaded condition (p=0.008). Similarly, the left and right corpora
      cavernosa values for the unloaded condition were 252% and 232% greater,
      respectively, than the loaded condition (p=0.02-0.03). Cavernous spaces that
      house penile arteries and nerves were compressed maximally below the pubic
      symphysis. Because this location of peak compression was not different between
      subjects, it may be a universal impingement zone that limits blood flow and
      neural activity to and from the penis. This information can be used to optimize
      seat design and thus reduce perineal injuries.

PMID- 16423358
TI  - Corrected thermodynamic description of adsorption via formalism of the theory of
      volume filling of micropores.
AB  - Based on the series of benzene adsorption and related enthalpy of adsorption data
      measured on porous carbons that possess various porous structures, we show that
      the creation of a solidlike structure in pores depends on the average pore
      diameter of an adsorbent. Taking into account the solidlike adsorbed phase in the
      thermodynamic description of the adsorption process via the formalism of the
      theory of volume filling of micropores (TVFM) leads to very good agreement
      between the data measured experimentally and those calculated from TVFM. Finally
      we show that the boundary between solidlike and liquidlike structures of benzene
      molecules in carbon pores is located around the average pore diameter, close to
      ca. 2.1-2.4 nm.

PMID- 16423359
TI  - Optimal shapes for adhesive binding between two elastic bodies.
AB  - The pull-off force required to separate two elastic bodies in adhesive binding
      depends on the surface shapes of the corresponding binding regions on the two
      bodies. Given a fixed binding area A, the optimal shapes are those which give the
      maximum pull-off force sigma(th)A where sigma(th) is the theoretical strength of
      interactive forces between the two solids. Here we study closed form solutions to
      the optimal shapes for adhesive binding over a small circular region where slip
      is allowed whenever shear stress along the contact interface exceeds a critical
      value.

PMID- 16423360
TI  - Physico-chemical characterization and photocatalytic activity of zinc oxide
      prepared by various methods.
AB  - Zinc oxide was prepared by different methods by varying precipitating agents, the
      source of the salt precursors and the microwave irradiation time and was
      characterized by XRD, BET-surface area, surface acidity and crystallite sizes.
      The photocatalytic reactions were carried out under solar radiation in batch
      reactors towards oxidation of 4-nitrophenol and reduction of Cr(VI) by varying
      different parameters such as irradiation time, pH of the solution, catalyst
      amount and substrate concentration and the activities were correlated with the
      physico-chemical parameters. Zinc oxide samples prepared by microwave irradiation
      and calcined at 300 degrees C exhibit highest surface area, acid sites and lowest
      crystallite sizes and show highest activity towards photocatalytic reactions.

PMID- 16423361
TI  - Colloidal aggregation phenomena: Spatial structuring of TEOS-derived silica
      aerogels.
AB  - In this contribution, the homogeneity of silica aerogels made from tetraethyl
      orthosilicate (TEOS) was studied by means of Fourier transform infrared (FTIR)
      and 29Si nuclear magnetic resonance (NMR) spectroscopies. FTIR spectra show a
      slight difference in the asymmetric Si-O-Si stretching vibration frequency in the
      outer and inner part of the aerogels. According to the 29Si NMR data, a higher
      relation Q4/Q3 was obtained in the inner parts of the gels compared with their
      outer parts, proving the difference in the cross linkage of the silica network.
      The obtained results are interpreted in terms of the specific spatial structuring
      of the colloidal suspensions due to the presence of gravity.

PMID- 16423362
TI  - Deformation of water droplets on solid surface in electric field.
AB  - The purpose of this paper is to analyze the deformation of water droplets on a
      solid surface under electric stress. A mathematical model making it possible to
      simulate the axisymmetric as well as non-axisymmetric deformations of droplets is
      developed. According to this model, the droplet deformation depends on several
      parameters such as the volume and the number of droplets, the conductivity and
      the permittivity of droplets, their proximity to one another, the surface of the
      solid material, and the location of each droplet on the dielectric surface. The
      results of the simulation show the disturbance of the background field through
      the presence of a single or multiple droplets. An experimental study is also
      achieved by considering one to three droplets aligned simultaneously on a
      dielectric smooth surface between two electrodes subjected to AC voltages. The
      influence of the background field and the droplet location regarding the
      electrodes on the deformation of water droplets are evidenced.

PMID- 16423363
TI  - The controlling effect of pH on oxidation of Cr(III) by manganese oxide minerals.
AB  - Oxidation of Cr(III) by three types of manganese oxide minerals (birnessite I,
      birnessite II, and todorokite) and effects of pH were investigated by chemical
      analysis, equilibrium redox, X-ray diffraction (XRD), and transmission electron
      microscopy. The effects of pH in the reaction systems on the oxidation of Cr(III)
      were similar among the three manganese oxide minerals. As pH increased from pH
      2.0, the amount of Cr(III) oxidized by the tested manganese oxide minerals first
      increased, and then peaked at pH 3.0-3.5. While pH continually increased from 3.0
      to 3.5, the amount of Cr(III) oxidized by the manganese oxide minerals sharply
      decreased. Until pH was higher than 5.0-5.5, the Cr(III) oxidation amounts
      changed to a small extent or kept stable. pH influenced the oxidation of Cr(III)
      mainly by altering the redox potential in the system, i.e., the concentration of
      H+, the species of Cr(III), and their distributions in the system. However, the
      surface charge of the manganese oxide minerals, subjected to the pH in the
      system, was not found to greatly influence the extent of the oxidation. When pH
      was below 5.0, oxidation of Cr(III) by the manganese oxide minerals was (or
      tended to be) an equilibrium reaction and was controlled thermodynamically. When
      pH was above 5.0-5.5, Cr(OH)3 precipitate was produced in the system and pH had
      little effect on the oxidation content of Cr(III).

PMID- 16423364
TI  - Bacterial cell microarrays for the detection and characterization of antibodies
      against surface antigens.
AB  - Bacterial cell surface antigens interact with the host immune system resulting in
      the production of antibodies. Detection of antibodies against surface antigens
      has applications in diagnosis of many bacterial infections, assessment of immune
      status and epidemiological studies. We developed a microarray platform, for
      antibody detection, by printing Gram-negative and Gram-positive whole bacterial
      cells on nitrocellulose coated glass substrates. Antibody binding was detected
      using fluorophore labeled secondary antibodies. The sensitivity of antibody
      detection was found to be 0.1 microg/ml. Using bacterial cell microarrays it was
      also possible to successfully detect antibodies against Francisella tularensis in
      canine serum samples declared positive for tularemia based on microagglutination
      antibody titer. Use of bacterial cells as the antigen source in immunoassays has
      the advantages of simulating in vivo presentation of surface antigens and also
      eliminating the need for antigen purification. The microarray format gives the
      added advantage of simultaneous detection of antibodies against multiple bacteria
      employing only small amounts of samples and reagents.

PMID- 16423365
TI  - Dynamic and label-free monitoring of natural killer cell cytotoxic activity using
      electronic cell sensor arrays.
AB  - A microelectronic sensor-based platform, the RT-CES (real time electronic
      sensing) system, is introduced for label free assessment of natural killer (NK)
      cell-mediated cytotoxic activity. The RT-CES system was used to dynamically and
      quantitatively monitor NK-mediated cytotoxic activity towards 8 different
      adherent target cell lines, including cancer cell lines commonly used in
      laboratories. The cytotoxic activity monitored by RT-CES system was compared with
      standard techniques such as MTT measurement and shows good correlation and
      sensitivity. To test the specificity of the assay, pharmacological agents that
      inhibit NK cell degranulation and cytotoxic activity were employed and were shown
      to selectively and dose-dependently inhibit NK-mediated cytotoxic activity toward
      target cells. In summary, the RT-CES system offers fully automated measurement of
      cytotoxic activity in real time, which enables large-scale screening of chemical
      compounds or genes responsible for the regulation of NK-mediated cytotoxic
      activity.

PMID- 16423366
TI  - Motor unit number estimates--from A to Z.
AB  - Quantitation has become an increasingly important part of clinical EMG. Most
      aspects of peripheral nerve and muscle function can be evaluated quantitatively
      using commonly available neurophysiologic methods. Because of the effects of
      collateral sprouting and reinnervation, techniques to measure the number of motor
      units supplying a muscle have been more difficult to develop. Motor unit number
      estimation (MUNE) consists of a number of different methods that evaluate the
      last unmeasured variable in nerve disease. The various MUNE techniques and their
      common technical issues will be reviewed, and potential clinical and research
      applications emphasized.

PMID- 16423367
TI  - Sporadic amyotrophic lateral sclerosis and breast cancer: Hyaline conglomerate
      inclusions lead to identification of SOD1 mutation.
AB  - Autopsy of patients with sporadic amyotrophic lateral sclerosis (ALS) rarely
      provides clues to a genetic etiology. We studied a 66-year-old woman who
      developed progressive weakness, fasciculations and upper motor neuron signs 1
      year after mastectomy and chemotherapy for a breast carcinoma. She died 14 months
      after the onset of neurological symptoms. Autopsy showed characteristic features
      of ALS but also with posterior column degeneration and conglomerate hyaline
      inclusions. These features suggested a mutation of SOD1 mutation although no
      other family members were affected. DNA analysis of autopsy tissue indicated an
      I113T SOD1 mutation.

PMID- 16423369
TI  - Cardioprotective effect of des-Aspartate-angiotensin-I (DAA-I) on cytokine gene
      expression profile in ligation model of myocardial infarction.
AB  - We investigate the influence of des-Aspartate-angiotensin-I (DAA-I) on the
      cytokine expression profile in a rodent model of myocardial infarction.
      Myocardial infarction model was created in female Wistar rats by coronary artery
      ligation. Animals were randomized to receive intravenously either a daily dose of
      1.2 mug DAA-I/kg body weight (group 1; n = 60) or saline (group 2; n = 60) for 14
      days after infarction. Heart function was assessed by echocardiography. Animals
      were euthanized at 1, 3, 7, 14 and 31 days. Morphometric analysis using
      tetrazolium chloride staining revealed that infarct size was reduced by 32.2% (p
      < 0.05) in group 1 after 14 days of DAA-I treatment. Left ventricular ejection
      fraction in group 1 improved significantly (73.4%) as compared to group 2 (47.7%;
      p < 0.001). Immunostaining for immune cells at the infarct site showed that CD8+
      lymphocytes infiltration at the infarct site declined in group 1 (15 +/- 5 cells)
      as compared to group 2 (50 +/- 6 cells; p < 0.001). Infiltration of monocytes and
      macrophages remained high at day 14 in group 2 (126 +/- 40 cells) as compared to
      group 1 (49 +/- 11 cells; p = 0.006). Multiplex PCR was done for differential
      gene expression of various pro-inflammatory cytokines. IL-6, TNF-alpha, TGF-beta
      and GM-CSF expression were significantly down-regulated in the infarct, peri
      infarct and contra-lateral zones of the left ventricle in group 1 as compared to
      group 2. IL-6, TGF-beta and GM-CSF expression started to decline from day 1 of
      DAA-I treatment while TNF-alpha expression only reduced after 7 days of DAA-I
      treatment. We conclude that DAA-I prevented infarct expansion through suppression
      of inflammatory cytokines and immune cell infiltration in the infarct region.

PMID- 16423370
TI  - Influence of in vitro and in vivo insulin treatment on the hormone (histamine,
      serotonin, endorphin and triiodothyronine) content of thymus and spleen cells.
AB  - Thymic and spleen cells were treated in vitro or in vivo with insulin. The in
      vitro treatments were done with 10(-6), 10(-9), 10(-12) and 10(-15) M
      concentrations for 30 min and after that histamine, serotonin, endorphin and
      triiodothyronine (T3) content of the cells were detected by using antibodies to
      the hormones and flow cytometry as well as confocal microscopy. For in vivo
      treatment 1 IU/kg insulin was given for adult rats and 1 h after that the target
      hormone contents were determined by the same manner. Histamine and T3 content
      radically decreased in the thymus after in vitro treatment independent on the
      insulin concentrations administered. In vivo treatment halved histamine and T3
      content. Serotonin content also decreased after in vitro treatment with the two
      higher concentrations, however the in vivo treatment did not cause a change.
      Histamine content was elevated after in vitro treatment in the spleen,
      independent on the insulin concentration. Endorphin level was not influenced at
      all. The experiments demonstrate that insulin is a factor which regulates the
      content (production, storage, secretion?) of some immunologically important
      molecules of the immune cells. Since each hormone molecule studied has important
      immunomodulatory role, the experiment points to the indirect immunomodulatory
      role of insulin.

PMID- 16423371
TI  - Metal ion and antioxidant alterations in leaves between different sexes of Ginkgo
      biloba L.
AB  - A comparative study was carried out to determine some valuable phytochemical
      components, macro- and microelement and redox parameters in leaves of male and
      female Ginkgo biloba trees and in extracts made from them. G. biloba extracts
      have become more popular as a therapeutic agent in the modern pharmacology in
      neurodegenerative diseases, in which increased brain metal levels can be observed
      and free radical reactions are involved. Macro- and microelement components,
      total phenol content, H-donating activity and reducing power as well as total
      scavenger capacity were determined in the samples. Well detectable differences
      were obtained for micro- and macroelement contents between male and female
      samples, but no toxic elements could be detected in the extracts. Male extracts
      contained more hazardous metals (e.g. Fe) compared to the female ones, while
      extracts from female leaves had higher levels of ions, which are known to have
      beneficial effects in neurodegenerative diseases. The ethanolic extracts of male
      leaves showed the highest H-donating activity, reducing power and total phenol
      content, as well as the best total scavenger activity. Ginkgo extracts due to the
      antioxidant properties may have favourable effects as dietary supplements in
      several neurodegenerative diseases, but this study draws the attention that
      critical evaluation is required in view of the potential hazard induced by their
      metal ion constitution. Our results lead us to the conclusion that although the
      aqueous extracts of female leaves are characterized by relatively lower
      antioxidant properties, they may be more eligible for these purposes due to their
      favourable metal ion constitution.

PMID- 16423372
TI  - Effect of a newly developed ketolide antibiotic, telithromycin, on metabolism of
      theophylline and expression of cytochrome P450 in rats.
AB  - The effects of a newly-developed ketolide antibiotic, telithromycin, on the
      metabolism of theophylline and the expression of hepatic cytochrome P450 (CYP)
      1A2 and CYP3A2 were investigated in rats. Telithromycin at a high dose (100 mg/kg
      of body weight) was injected intraperitoneally once a day for 3 days. Twenty-four
      hours (day 4) after the final administration of telithromycin, theophylline (10
      mg/kg) was administered intravenously. The presence of telithromycin
      significantly delayed the disappearance of theophylline from plasma. Parameters
      related to the pharmacokinetic interaction between theophylline and telithromycin
      were examined by noncompartmental methods. A significant decrease in the systemic
      clearance of theophylline was observed in the presence of telithromycin.
      Pretreatment with telithromycin significantly decreased the metabolic clearance
      of the major metabolites, 1-methyluric acid and 1,3-dimethyluric acid, with no
      change in the renal clearance of theophylline, suggesting that the decreased
      systemic clearance of theophylline by telithromycin is due to reduction of their
      metabolic clearance. Pretreatment with telithromycin significantly decreased the
      activity of 7-ethoxyresorufin O-deethylation and testosterone 6 beta
      hydroxylation, suggesting that telithromycin decreases the activity of hepatic
      CYP1A2 and CYP3A2. Western blot analysis revealed that telithromycin
      significantly decreased the protein levels of CYP1A2 and CYP3A2 in the liver,
      which could explain the observed decreases in the systemic clearance of
      theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric
      acid. The present study suggests that telithromycin at the dose used in this
      study alters the pharmacokinetics and metabolism of theophylline, due to
      reductions in the activity and expression of hepatic CYP1A2 and CYP3A2.

PMID- 16423373
TI  - Liver histopathology in Baltic flounder (Platichthys flesus) as indicator of
      biological effects of contaminants.
AB  - Results are presented of a study on liver histopathology in Baltic flounder
      (Platichthys flesus) carried out in 2001 and 2002 in four coastal sampling areas
      of the Baltic Sea: Kvadofjarden (Swedish east coast, reference area), Klaipeda
      Butinge (Lithuanian coast), Gulf of Gdansk (Polish coast), and Wismar Bay (German
      coast) within the framework of the EU-funded BEEP project. Liver lesions were
      diagnosed and categorised using standardised methodologies and, for a spatial and
      temporal assessment of the prevalence and types of lesions detected, a scoring
      system was applied, involving the calculation of mean histopathology lesion
      scores. 83.0% of the 436 female flounder examined (size range: 20-43 cm total
      length, age range: 2-8 years) were affected by liver lesions, out of which 74.3%
      were assigned to the category of non-specific, 3.4% to the category of early
      toxicopathic non-neoplastic, 4.6% to the category of pre-neoplastic and 0.7% to
      the category of neoplastic lesions. Mean lesions scores were highest in the areas
      at the Lithuanian and Swedish coast and there is indication of an impact of the
      age structure of the flounder populations studied, the sampling season as well as
      of contaminant effects.

PMID- 16423374
TI  - Bystander-induced differentiation: a major response to targeted irradiation of a
      urothelial explant model.
AB  - A ureter primary explant technique, using porcine tissue sections was developed
      to study bystander effects under in vivo like conditions where dividing and
      differentiated cells are present. Targeted irradiations of ureter tissue
      fragments were performed with the Gray Cancer Institute charged particle
      microbeam at a single location (2 microm precision) with 10 3He2+ particles (5
      MeV; LET 70 keV/microm). After irradiation the ureter tissue section was
      incubated for 7 days allowing explant outgrowth to be formed. Differentiation was
      estimated using antibodies to Uroplakin III, a specific marker of terminal
      urothelial differentiation. Even although only a single region of the tissue
      section was targeted, thousands of additional cells were found to undergo
      bystander-induced differentiation in the explant outgrowth. This resulted in an
      overall increase in the fraction of differentiated cells from 63.5+/-5.4% to
      76.6+/-5.6%. These changes are much greater than that observed for the induction
      of damage in this model. One interpretation of these results is that in the
      tissue environment, differentiation is a much more significant response to
      targeted irradiation and potentially a protective mechanism.

PMID- 16423375
TI  - Serous cutaneous glands of the Pacific tree-frog Hyla regilla (Anura, Hylidae):
      patterns of secretory release induced by nor-epinephrine.
AB  - The serous (poison) cutaneous glands of the Pacific tree-frog Hyla regilla were
      induced to release their product by 10(-3)M nor-epinephrine stimulation. After
      discharge structural and ultrastructural features of the cutaneous glands
      involved in release were observed. Furthermore, the discharged product,
      consisting of discrete, secretory granules, was collected and processed for
      transmission electron microscope analysis. As indicated by patterns found in the
      myoepithelium encircling the syncytial secretory unit, gland discharge is caused
      by contraction of the peripheral myocytes. Muscle cell compression dramatically
      affects the syncytium and results in degenerative changes, including expulsion of
      the secretory unit nuclei. Therefore, the structural collapse in depleted glands
      has been ascribed to the mechanical activity performed by the myoepithelium
      during discharge, rather than cytoplasm involution described in conventional,
      holocrine glands. TEM investigation revealed that the secretory granules
      collected after discharge maintain their peculiar traits: they consist of
      recurrent patterns of thin subunits, acquired during serous maturation and
      provided with remarkable structural stability.

PMID- 16423376
TI  - Removal of heavy metal ions from water by complexation-assisted ultrafiltration.
AB  - Toxic heavy metals in air, soil and water are global problems that are growing
      threat to the environment. Therefore, the removal and separation of toxic and
      environmentally relevant heavy metal ions are a technological challenge with
      respect to industrial and environmental application. A promising process for the
      removal of heavy metal ions from aqueous solutions involves bonding the metals to
      a bonding agent (such as macromolecular species), and then separating the loaded
      agents from wastewater by separation processes such as membrane filtration. The
      choice of water-soluble macroligands remains important for developing this
      technology. The effects of type of complexing agent, pH value and applied
      pressure on retention coefficients of Zn(II) and Cd(II) complexes were
      investigated. At best operating conditions (pH=9.0, p=300kPa) using
      diethylaminoethyl cellulose, the removal of Cd(2+) and Zn(2+) was more than 95%
      and 99%, respectively.

PMID- 16423377
TI  - Sorption kinetics and leachability of heavy metal from the contaminated soil
      amended with immobilizing agent (humus soil and hydroxyapatite).
AB  - Release of heavy metals onto the soil as a result of agricultural and industrial
      activities may pose a serious threat to the environment. This study investigated
      the kinetics of sorption of heavy metals on the non-humus soil amended with (1:3)
      humus soil and 1% hydroxyapatite used for in situ immobilization and leachability
      of heavy metals from these soils. For this, a batch equilibrium experiment was
      performed to evaluate metal sorption in the presence of 0.05 M KNO(3) background
      electrolyte solutions. The Langmuir isotherms applied for sorption studies showed
      that the amount of metal sorbed on the amended soil decreased in the order of
      Pb(2+)>Zn(2+)>Cd(2+). The data suggested the possibility of immobilization of Pb
      due to sorption process and immobilization of Zn and Cd by other processes like
      co-precipitation and ion exchange. The sorption kinetics data showed the pseudo
      second-order reaction kinetics rather than pseudo-first-order kinetics.
      Leachability study was performed at various pHs (ranging from 3 to 10).
      Leachability rate was slowest for the Pb(2+) followed by Zn(2+) and Cd(2+). Out
      of the metal adsorbed on the soil only 6.1-21.6% of Pb, 7.3-39% of Zn and 9.3
      44.3% of Cd leached out from the amended soil.

PMID- 16423378
TI  - Transformations of dissolved organic matter in a landfill leachate--a size
      exclusion chromatography/mass spectrometric approach.
AB  - The aim of the present study was to search for qualitative changes in the
      landfill leachate DOM along a groundwater gradient. The study was focused on DOM
      characteristics of importance for its interaction with pollutants, such as
      molecular weight distribution and aromaticity. It was concluded that the leachate
      DOM underwent substantial qualitative changes along the investigated gradient at
      the Vejen landfill, Denmark. The molecular weight decreased, the polydispersity
      increased, and the aromaticity varied with the lowest values found in the middle
      of the gradient. The high aromaticity in the end of the gradient may explain the
      higher DOM binding capacity towards hydrophobic compounds seen earlier in these
      samples. The relative abundance of ions with mass to charge ratio (m/z) of 600
      1200 seemed to be very stable along the gradient, indicating that the observed
      qualitative changes of the DOM is mostly attributed to changes in the m/z 100-600
      range. The DOM seemed to become more similar to fulvic acids present in
      uncontaminated groundwater with respect to molecular weight and polydispersity
      along the gradient.

PMID- 16423379
TI  - Bioaccumulation of cyclopenta[cd]pyrene and benzo[ghi]fluoranthene by mussels
      transplanted in a coastal lagoon.
AB  - The bioaccumulation of two isomeric non-alternant non-priority polycyclic
      aromatic hydrocarbons (PAHs), namely cyclopenta[cd]pyrene and
      benzo[ghi]fluoranthene, was investigated in caged mussels (Mytilus
      galloprovincialis) exposed for 30 days in three sites of a coastal lagoon
      (Pialassa Baiona, Ravenna, Italy) contaminated by pyrogenic PAHs. The
      concentration of cyclopenta[cd]pyrene and benzo[ghi]fluoranthene increased from
      undetectable levels in reference mussels withdrawn from the Adriatic sea to 10-30
      ng g(-1) dry weight in transplanted mussels. Other contaminants bioaccumulated by
      caged mussels included pyrene, fluoranthene and mercury. Whilst the isomer
      concentration ratio pyrene/fluoranthene in biota was comparable to that observed
      in sediments, the cyclopenta[cd]pyrene/benzo[ghi]fluoranthene ratio was much
      lower in mussels than in sediments. The lower sediment biota accumulation factor
      of cyclopenta[cd]pyrene with respect to that of benzo[ghi]fluoranthene was
      tentatively attributed to the greater biological activity of the former compound,
      which contains a reactive olefinic bond in the cyclopenta fused ring moiety.
      Given the higher mutagenic activity of cyclopenta[cd]pyrene with respect to other
      priority PAHs, its bioaccumulation from contaminated sediments may rise
      considerably the overall toxicity of PAH residues in exposed biota.

PMID- 16423380
TI  - Biochemical stress response in freshwater fish Channa punctatus induced by
      aqueous extracts of Euphorbia tirucalli plant.
AB  - Piscicidal activities of aqueous extracts of Euphorbia tirucalli were very well
      established, but their ultimate mode of action on fish metabolism was not yet
      known. Exposure of fishes over 24h or 96h to sub-lethal doses (40% and 80% of
      LC(50)) of aqueous extract of E. tirucalli stem-bark and latex, significantly
      (P<0.05) altered the level of total protein, total free amino acids, nucleic
      acids, glycogen, pyruvate, lactate and activity of protease, alanine
      aminotransferase, aspartate aminotransferase, acetylcholinesterase and cytochrome
      oxidase enzyme in liver and muscle tissues of freshwater fish Channa punctatus.
      The alterations in all these biochemical parameters were significantly (P<0.05)
      time- and dose-dependent. After 7d of withdrawal of treatment of 80% of LC(50) of
      E. tirucalli extracts shows that there was a partial recovery in the levels of
      glycogen but nearly complete recovery in total protein, total free amino acids,
      pyruvate, lactate, nucleic acids level and activity of protease, aspartate
      aminotransferase, alanine aminotransferase, acetylcholinesterase and cytochrome
      oxidase enzyme in both the tissues of fish. Thus aqueous extracts of E. tirucalli
      adversely affect respiratory pathway of fish and cause energy crisis during
      stress by suppressing ATP production. The reversibility of the action of the
      aqueous extracts would be an additional advantage in their use.

PMID- 16423381
TI  - Inhibin/activin subunits beta-A (-betaA) and beta-B (-betaB) are differentially
      localised in normal, hyperplastic and malignant human endometrial tissue.
AB  - Inhibins (INHs) are dimeric glycoproteins composed of an alpha (-alpha) subunit
      and one of two possible beta (beta-) subunits (betaA or betaB). The aims of this
      study were to determine the frequency and distribution of INH beta (betaA and
      betaB) subunits in normal, hyperplastic and malignant human endometrium.
      Endometrial tissue was obtained from normal, hyperplastic (simple, complex and
      atypical) and endometrioid adenocarcinoma (EC) and INH-alpha, -betaA and -betaB
      were labelled using immunohistochemistry and immunofluorescence. INH-betaA and 
      betaB labelling was increased significantly between the proliferative and
      secretory phase (p<0.05). The lowest labelling was demonstrated in EC, being
      significantly lower than in secretory phase (p<0.01) and in simple, complex and
      atypical hyperplastic tissue (p<0.05). For inhibin-betaB, the most intense
      labelling was noted in atypical hyperplasia compared to EC (p<0.05). A strong
      colocalisation of inhibin-alpha and -betaA could be demonstrated in malignant
      endometrial tissue, suggesting the production of inhibin A within the tumour.
      Additionally, only limited colocalisation of inhibin-betaB with -alpha subunit
      could be observed, suggesting the synthesis of activin B rather than inhibin B in
      malignant endometrium. In conclusion, INH-betaA and -betaB were labelled in
      normal, hyperplastic and malignant endometrium. Hyperplastic tissue labelled more
      intensely than EC for the presence of INH-betaA and -betaB, suggesting a
      substantial function in endometrial pathogenesis and an important role in
      endometrial carcinogenesis.

PMID- 16423382
TI  - Long-term suppression of fertility in female giraffe using the GnRH agonist
      deslorelin as a long-acting implant.
AB  - Zoological institutions provide an environment conducive to studying proximate
      mechanisms influencing reproduction that can provide guidance to both field and
      captive settings seeking to manage their stock. Both national parks and zoos have
      space limitations that sometimes require the use of reversible contraception in
      order to reduce reproductive rate or limit specific individuals from reproducing.
      We designed a study to test the efficacy of a long-lasting contraceptive in
      female giraffe by monitoring reproductive endocrinology and behavior. We
      implanted two animals with the GnRH agonist deslorelin and monitored their
      endocrine status using fecal steroid analysis. We have previously validated an
      assay for fecal pregnanes and here we report our validation for fecal estrogens.
      Both sex steroid concentrations were suppressed in two females, although one
      female exhibited an immediate post-implantation positive feedback response.
      Sexual activity nearly disappeared in one animal, whereas the other showed
      regular sexual behavior. The contraceptive effect lasted for at least 472 d, and
      successfully suppressed estrous cyclicity in one female for >2 y. We conclude
      that deslorelin implants provide a minimally invasive means for long-term
      suppression of reproduction in female giraffe.

PMID- 16423383
TI  - Nuclear status of immature and mature stallion spermatozoa.
AB  - 'The highly packed chromatin of mature spermatozoa results from replacement of
      somatic-like histones by highly basic arginine- and cysteine-rich protamines
      during spermatogenesis, with additional conformational changes in chromatin
      structure during epididymal transit. The objective of the present study was to
      compare the nuclear characteristics of immature and mature epididymal stallion
      spermatozoa, using a variety of experimental approaches. Resistance to in vitro
      decondensation of chromatin, following exposure to SDS-DTT and alkaline
      thioglycolate, increased significantly in mature spermatozoa. Evaluation of the
      thiol-disulfide status (monobromobimane labeling) demonstrated that immature
      cells obtained from ductulli efferentes contained mostly thiol groups, whereas
      these groups were oxidized in mature cells collected from the cauda epididymidis.
      Based on atomic absorption spectrophotometry, maturation of stallion spermatozoa
      was accompanied by a 60% reduction in the Zn(2+) content of sperm cells,
      concomitant with increased concentrations of this ion in epididymal fluid.
      Furthermore, the degree of disulfide bonding was inversely correlated with
      susceptibility of chromatin to acid denaturation (SCSA). Collectively, these data
      were consistent with the hypothesis that maturation of stallion spermatozoa
      involves oxidation of sulphydryl groups to form intra- and intermolecular
      disulfide links between adjacent protamines, with loss of zinc as an integral
      feature. These changes endow mechanical and chemical resistance to the nucleus,
      ensuring efficient transmission of the paternal genome at fertilization.

PMID- 16423384
TI  - Characterization of nanofilled compared to universal and microfilled composites.
AB  - OBJECTIVES: The purpose of this study was to compare the inorganic fraction and
      the mechanical properties of three nanofilled composites with four universal
      hybrid and two microfilled composites. The degrees of conversion of the materials
      photopolymerized using halogen and LED units were also investigated. METHODS:
      Three nanofilled (Supreme, Grandio and Grandio Flow), four universal hybrid
      (Point-4, Tetric Ceram, Venus, Z 100) and two microfilled (A 110, Durafill VS)
      composites were used in this study. Their filler weight content was measured by
      thermogravimetric analysis. The morphology of the filler particles was determined
      using scanning-electron microscopy (SEM). Mechanical properties were measured:
      dynamic and static elastic moduli, flexural strength and Vickers microhardness.
      The degree of conversion in relation with the depth of polymerization of every
      material tested was evaluated using Raman spectrophotometry. RESULTS: Nanofilled
      resin composites show higher elastic moduli than those of universal and
      microfilled composites, except for the Z-100. The microfilled composites exhibit
      by far the lowest mechanical properties. The flexural strength does not appear as
      a discriminating factor in this study. The degrees of polymerization obtained
      with the halogen lamp are higher than those obtained with the LED lamp.
      SIGNIFICANCE: Nanofilled resin composites show mechanical properties at least as
      good as those of universal hybrids and could thus be used for the same clinical
      indications as well as for anterior restorations due to their high aesthetic
      properties.

PMID- 16423386
TI  - The effect of mold temperature on castability of CP Ti and Ti-6Al-4V castings
      into phosphate bonded investment materials.
AB  - OBJECTIVE: The aim of this study was to evaluate the castability of CP titanium
      and Ti-6Al-4V alloy castings into Rematitan Plus investment at three different
      mold temperatures. METHODS: A nylon mesh pattern (20 mm with 64 squares and wire
      of 0.7 mm in diameter) was used for the castability testing. Initially, an image
      of the wax pattern was obtained by means of a digital camera and the total
      extension of filaments (mm) was then measured, using the Leica Qwin image
      analysis system. The mesh sprued was placed in the Rematitan Plus investment
      material and the castings were made in a Discovery Plasma machine at three
      different mold temperatures: 430 degrees C (control group), 480 degrees C or 530
      degrees C. Ten castings were made for each temperature. The images of the
      castings were analyzed (Leica Qwin) and the castability index determined by the
      number of the completely cast segments as a percentage of the wax pattern. Data
      were analyzed by two-way ANOVA and Tukey's multiple comparison test (a = 0.05)
      using materials and temperatures as discriminating variables. RESULTS: The Ti-6Al
      4V alloy (60.86%) presented a better castability index than CP Ti (48.44%) (p <
      0.000001). For CP Ti, the temperature of 530 degrees C (23.96%) presented better
      castability than at other temperatures, 480 degrees C (14.66%) and 430 degrees C
      (12.54%), with no difference between them (p < 0.001). For Ti-6Al-4V alloy, there
      was a statistically significant difference among the three temperatures: 530
      degrees C (28.36%) > 480 degrees C (19.66%) > 430 degrees C (15.97%) (p < 0.002).
      SIGNIFICANCE: Within the limitations of this study, the increase in the mold
      temperature of the Rematitan Plus investment resulted in a better castability
      index for both materials, and Ti-6Al-4V presented a better castability index than
      CP Ti.

PMID- 16423385
TI  - Study of shrinkage-strain and contraction rates of commercial and experimental
      compomers.
AB  - OBJECTIVE: To asses the contraction rate and shrinkage-strain of a new
      experimental compomer in comparison with four commercial compomers and a flowable
      composite resin. METHOD: Shrinkage-strain and contraction rate were calculated by
      measuring the deflection of a disc in a developed instrument using "bonded disk"
      method. RESULTS: Both shrinkage-strain and contraction rate are reported. Total
      shrinkage-strain for compomer systems varies from 2.59 to 3.34%, whereas the
      flowable composite resin showed a value of 3.50%. The contraction rate for
      compomers varies from 81.60 to 109.80 microm/min, whereas the flowable composite
      resin obtained 141.6 microm/min. Commercial compomers show a lower contraction
      rate than the control group, whereas the experimental group only shows
      statistical differences with a commercial compomer (Dyract AP). SIGNIFICANCE: The
      shrinkage-strain and contraction rate results for the experimental compomer are
      as good as those obtained for a commercial flowable compomer and a flowable
      composite resin. The contraction rates of all compomers could be directly related
      to polymerization rates. The method used to measure shrinkage-strain and
      contraction rate is adequate because it simulates conditions in situ. It can be
      inferred that the contraction rate is directly related to shrinkage-strain.

PMID- 16423387
TI  - Two-step purification of outer membrane proteins.
AB  - Here, we describe a simple and efficient method for the purification of
      Escherichia coli outer membrane proteins. We have tested this protocol for the
      purification of Wza and Osmoporin C (OmpC) proteins. Both proteins were purified
      to homogeneity, in two steps, by anion exchange and size exclusion chromatography
      with a final yield of 92.5 mg for the Wza protein and 291.5 mg for the OmpC
      protein. The purity of the samples was judged by electrophoretic analysis, mass
      spectrometry, single particle analysis, three-dimensional (3D) crystallisation
      and X-ray diffraction.

PMID- 16423388
TI  - Structure and properties of clinical coralline implants measured via 3D imaging
      and analysis.
AB  - The development and design of advanced porous materials for biomedical
      applications requires a thorough understanding of how material structure impacts
      on mechanical and transport properties. This paper illustrates a 3D imaging and
      analysis study of two clinically proven coral bone graft samples (Porites and
      Goniopora). Images are obtained from X-ray micro-computed tomography (micro-CT)
      at a resolution of 16.8 microm. A visual comparison of the two images shows very
      different structure; Porites has a homogeneous structure and consistent pore size
      while Goniopora has a bimodal pore size and a strongly disordered structure. A
      number of 3D structural characteristics are measured directly on the images
      including pore volume-to-surface-area, pore and solid size distributions, chord
      length measurements and tortuosity. Computational results made directly on the
      digitized tomographic images are presented for the permeability, diffusivity and
      elastic modulus of the coral samples. The results allow one to quantify
      differences between the two samples. 3D digital analysis can provide a more
      thorough assessment of biomaterial structure including the pore wall thickness,
      local flow, mechanical properties and diffusion pathways. We discuss the
      implications of these results to the development of optimal scaffold design for
      tissue ingrowth.

PMID- 16423389
TI  - The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite
      thin films.
AB  - Magnetron co-sputtering has been employed to fabricate thin nanocrystalline
      coatings of silicon-substituted hydroxyapatite (SiHA) of different Si
      compositions: 0.8 wt%, 2.2 wt%, and 4.9 wt%. A human osteoblast-like (HOB) cell
      model was used to study the long-term interaction between the HOB cells and
      coatings in vitro. Results showed that the number of cells growing on all coated
      titanium (Ti) samples were statistically significantly higher than on uncoated
      Ti. In addition, HOB cells growing on all SiHA surfaces displayed enhanced cell
      spreading, with extensive extracellular matrix synthesis. DNA staining revealed
      normal phenotype nuclear morphology for HOB cells, with several dense chromosomes
      surrounded by a periphery of intact nuclear membrane. Furthermore,
      immunofluorescent staining indicated that cells showed improved adhesion on the
      coated surfaces with increasing Si content, developing mature cytoskeletons with
      numerous distinct and well-defined actin stress fibres in the cell membranes.
      Results also demonstrated that the bone mineralisation process was greatest in
      the presence of the highest Si level (4.9 wt%). However, at very early culturing
      time point, cells did not attach so readily on the surface of this coating due to
      rapid dissolution. Thus, this work suggests that a Si content of 2.2 wt% may be
      the optimum loading to improve the bioactive property of HA thin films.

PMID- 16423390
TI  - Fabrication methods of porous metals for use in orthopaedic applications.
AB  - Implant stability is not only a function of strength but also depends on the
      fixation established with surrounding tissues [Robertson DM, Pierre L, Chahal R.
      Preliminary observations of bone ingrowth into porous materials. J Biomed Mater
      Res 1976;10:335-44]. In the past, such stability was primarily achieved using
      screws and bone cements. However, more recently, improved fixation can be
      achieved by bone tissue growing into and through a porous matrix of metal,
      bonding in this way the implant to the bone host. Another potentially valuable
      property of porous materials is their low elastic modulus. Depending on the
      porosity, moduli can even be tailored to match the modulus of bone closer than
      solid metals can, thus reducing the problems associated with stress shielding.
      Finally, extensive body fluid transport through the porous scaffold matrix is
      possible, which can trigger bone ingrowth, if substantial pore interconnectivity
      is established [Cameron HU, Macnab I, Pilliar RM. A porous metal system for joint
      replacement surgery. Int J Artif Organs 1978;1:104-9; Head WC, Bauk DJ, Emerson
      Jr RH. Titanium as the material of choice for cementless femoral components in
      total hip arthroplasty. Clin Orthop 1995;85-90]. Over the years, a variety of
      fabrication processes have been developed, resulting in porous implant substrates
      that can address unresolved clinical problems. The advantages of metals
      exhibiting surface or bulk porosity have led researchers to conduct systematic
      research aimed at clarifying the fundamental aspects of interactions between
      porous metals and hard tissue. This review summarises all known methods for
      fabricating such porous metallic scaffolds.

PMID- 16423391
TI  - Dopamine-induced graded intracellular Ca2+ elevation via the Na+Ca2+ exchanger
      operating in the Ca2+-entry mode in cockroach salivary ducts.
AB  - Stimulation with the neurotransmitter dopamine causes an amplitude-modulated
      increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in epithelial
      cells of the ducts of cockroach salivary glands. This is completely attributable
      to a Ca(2+) influx from the extracellular space. Additionally, dopamine induces a
      massive [Na(+)](i) elevation via the Na(+)K(+)2Cl(-) cotransporter (NKCC). We
      have reasoned that Ca(2+)-entry is mediated by the Na(+)Ca(2+) exchanger (NCE)
      operating in the Ca(2+)-entry mode. To test this hypothesis, [Ca(2+)](i) and
      [Na(+)](i) were measured by using the fluorescent dyes Fura-2, Fluo-3, and SBFI.
      Inhibition of Na(+)-entry from the extracellular space by removal of
      extracellular Na(+) or inhibition of the NKCC by 10 microM bumetanide did not
      influence resting [Ca(2+)](i) but completely abolished the dopamine-induced
      [Ca(2+)](i) elevation. Simultaneous recordings of [Ca(2+)](i) and [Na(+)](i)
      revealed that the dopamine-induced [Na(+)](i) elevation preceded the [Ca(2+)](i)
      elevation. During dopamine stimulation, the generation of an outward Na(+)
      concentration gradient by removal of extracellular Na(+) boosted the [Ca(2+)](i)
      elevation. Furthermore, prolonging the dopamine-induced [Na(+)](i) rise by
      blocking the Na(+)/K(+)-ATPase reduced the recovery from [Ca(2+)](i) elevation.
      These results indicate that dopamine induces a massive NKCC-mediated elevation in
      [Na(+)](i), which reverses the NCE activity into the reverse mode causing a
      graded [Ca(2+)](i) elevation in the duct cells.

PMID- 16423393
TI  - Classification and scoring systems in myelodysplastic syndromes: a retrospective
      analysis of 311 patients.
AB  - The main objective of this study was to evaluate the role of the recent World
      Health Organization (WHO) classification for assessing prognosis in patients with
      myelodysplastic syndromes (MDS). To this effect, we analyzed the prognostic
      impact of the WHO and French-American-British (FAB) morphologic classifications
      and of four different scoring systems in a series of 311 patients with primary
      MDS diagnosed between October 1990 and June 2001. Both the FAB and WHO
      classifications identified groups with different prognoses (p<0.0001), those
      presenting refractory anemia (RA) and refractory anemia with ringed sideroblasts
      (RARS) showing the best prognosis. The WHO classification subdivided RA into RA
      with only red cell dysplasia, and refractory cytopenia with multilineage
      dysplasia (RCMD), and RARS into RARS plus refractory cytopenia with multilineage
      dysplasia and ringed sideroblast (RCMD-RS). In our population, we have shown that
      the two subtypes characterized by dysplasia affecting exclusively the erythroid
      population (RA and RARS) have a better prognosis, with a median survival of 122.2
      and 81.9 months, respectively, than those with multilineage dysplasia (RCMD and
      RCMD-RS) with a median survival of 32.3 and 43.2 months, respectively. There were
      no significant differences in median survival comparing RA with RAS (p<0.95), or
      comparing RCMD with RSCMD (p<0.97). Besides, the four scoring systems
      discriminated our MDS patients in terms of survival, and an increase in
      prognostic capacity was achieved on adding the score to the morphological
      classifications. Risk scoring had a greater prognostic impact than the FAB and
      WHO classifications. Prognostic scoring systems may be an important tool for risk
      stratification in hematological practice, and add significance to morphological
      classification. Combined application of the WHO classification and score system
      is useful for improving the identification of patients with a poorer prognosis.
      The WHO classification establishes more homogeneous subcategories than the FAB
      classification and is also able to identify groups with different prognoses.

PMID- 16423392
TI  - Ganoderma lucidum causes apoptosis in leukemia, lymphoma and multiple myeloma
      cells.
AB  - Over many centuries, herbal remedies have treated a variety of ailments. This
      empiric observational approach has produced a number of leads for formulated
      medicines. Ganoderma lucidum extract was screened for its anti-proliferative
      activity using a panel of 26 human cancer cell lines. The six most sensitive
      hematologic cell lines were: HL-60 (ED50 26 microg/ml), U937 (63 microg/ml), K562
      (50 microg/ml), Blin-1 (38 microg/ml), Nalm-6 (30 microg/ml) and RPMI8226 (40
      microg/ml). Cell cycle analyses revealed a G2/M arrest, most prominently in HL-60
      cells. Four hematopoietic cell lines (HL-60, Blin-1, U937, RPMI8226) were
      examined for apoptosis, which ranged between 21 and 92%. After exposure to G.
      lucidum extract, HL-60 cells became multinucleated with an increased DNA content.
      These results indicate that G. lucidum extract has a profound activity against
      leukemia, lymphoma and multiple myeloma cells and may be a novel adjunctive
      therapy for the treatment of hematologic malignancies.

PMID- 16423394
TI  - Immunomodulatory effects of beta-glucan on neutrophil function in fathead minnows
      (Pimephales promelas Rafinesque, 1820).
AB  - Stimulatory effects of yeast beta-1,3-1,6-glucans on neutrophils have long been
      recognized, but effects of glucans on degranulation of primary granules in fish
      neutrophils have not been previously reported. Neutrophil function was monitored
      during in vitro and in vivo application of glucans to non- (NS), acute- (AS) and
      chronically stressed (CS) fish. beta-Glucan proved to be a strong and quick (80%,
      2 min) stimulant of degranulation. Dietary glucan increased degranulation in NS
      fish, and prevented a decrease in AS fish. Degranulation in CS fish returned to
      NS levels 3 days after the glucan diet was fed. Fathead minnows appear to be a
      useful model to investigate neutrophil degranulation in fish exposed to different
      environmental conditions and immunomodulators. Use of beta-glucans in fish diets
      prior to AS and during chronic stress can enhance neutrophil function,
      potentially increasing disease resistance and survival rates after transportation
      or exposure to poor water quality.

PMID- 16423395
TI  - Mad1 is a transcriptional repressor of Bcl-6.
AB  - Bcl-6, a major regulator of B lymphocyte function that contributes to neoplastic
      transformation of B cells, is expressed in activated germinal center (GC) B cells
      and down-regulated during terminal differentiation to plasma cells. Regulation of
      Bcl-6 expression is incompletely characterized. Terminal B cell differentiation
      is associated with down-regulation of Bcl-6, activation of Blimp-1, modulation of
      Myc, and specifically with the up-regulation of the Mad1 and Mad4 transcription
      factors, which play a critical role in cell differentiation and cell cycle
      regulation. Because the Mad E-box consensus binding site is present in the
      upstream promoter of Bcl-6, we investigated whether Bcl-6 may be under control of
      the Mad1 transcription factor. Anti-sense Mad1 oligonucleotides abrogated the
      down-regulation of Bcl-6 expression that occurred during in vitro differentiation
      of mouse splenic B cells induced by dextran-conjugated anti-IgD Ab and IL-5.
      Transduction of the WEHI 231 B cell line with retroviruses expressing Mad1 down
      regulated Bcl-6 expression. Expression of the 5' upstream promoter region of Bcl
      6 was down-regulated by co-expression of Mad1. Last, chromatin
      immunoprecipitation assays with anti-Mad1 Ab demonstrated in vivo interaction of
      Mad1 with the Bcl-6 promoter region. The findings suggest that Mad1 is a
      transcriptional repressor of Bcl-6.

PMID- 16423396
TI  - Proteasomes and antigen presentation: evidence that a KEKE motif does not promote
      presentation of the class I epitope SIINFEKL.
AB  - Previously we proposed that stretches of alternating Lys(K) and Glu(E) in
      polypeptides promote the expression of nearby sequences on Class I molecules
      [Realini, C., Rogers, S.W., Rechsteiner, M., 1994. KEKE motifs. Proposed roles in
      protein-protein association and presentation of peptides by MHC class I
      receptors. FEBS Lett. 348, 109-113]. As a test of the KEKE hypothesis we have
      employed osmotic lysis of pinosomes and transfection to introduce or express
      various ubiquitin peptide fusion proteins in the cytosol of wild type and
      PA28alphabetagamma- mouse embryo fibroblasts. KEKE or non-KEKE motifs were placed
      between ubiquitin and the OVA epitope SIINFEKL that was at or near the C-termini
      of the various fusion proteins. Measurements of surface Kb-SIINFEKL complexes
      using the monoclonal antibody 25.-D1.16 allowed us to assess the effects of
      upstream KEKE motifs and PA28 status on SIINFEKL surface presentation. KEKE
      motifs did not enhance presentation of the OVA epitope. However, our studies did
      confirm that PA28alphabeta is needed for efficient SIINFEKL surface expression
      when hsp90 is inhibited.

PMID- 16423397
TI  - Autoreactivity of primary human immunoglobulins ancestral to hypermutated human
      antibodies that neutralize HCMV.
AB  - The human antibody response to the AD-2S1 epitope of glycoprotein B (gB) of human
      cytomegalovirus (HCMV) is dominated by a family of closely related somatically
      mutated antibodies. These antibodies neutralize viral infectivity and the genes
      encoding them are derived from two commonly used germ-line variable (V) region
      genes, IGHV3-30 and IGKV3-11. Recombination of these V genes with the appropriate
      junctional diversity generates genes that encode primary immunoglobulins that
      bind to AD-2S1. To further understand the initial primary immunoglobulin response
      to AD-2S1 we synthesized the germ-line-based ancestor of one such family of
      antibodies and showed that it bound gB at the AD-2S1 epitope. Here we show that
      the germ-line ancestor of a second family of antibodies likewise binds to gB. We
      further show that one of the ancestral primary immunoglobulins, but not the
      other, also recognized autoantigens. In contrast, the hypermutated derivatives
      did not demonstrate autoreactivity and minor structural changes in the primary
      immunoglobulin were sufficient to generate or abolish autoreactivity or to change
      specificity. Thus, our demonstration that the ancestor of a highly mutated, non
      autoreactive antiviral IgG antibody binds nuclear and cell-surface autoantigens
      indicates for the first time that self-reactivity is not necessarily a barrier to
      development into a follicular B lymphocyte that undergoes antigen-initiated
      affinity maturation.

PMID- 16423398
TI  - Sodium butyrate up-regulates cathelicidin gene expression via activator protein-1
      and histone acetylation at the promoter region in a human lung epithelial cell
      line, EBC-1.
AB  - The antimicrobial protein cathelicidin is considered to play an important role in
      the defense mechanisms against bacterial infection. Recent studies show that
      sodium butyrate induces cathelicidin gene expression in human colonic, gastric
      and hepatic cells. However, little is known about the precise regulatory
      mechanisms underlying sodium butyrate-induced cathelicidin gene expression. In
      this study, we examined the regulatory mechanisms involved in sodium butyrate
      induced cathelicidin gene expression using a human lung epithelial cell line, EBC
      1. Our results indicate that sodium butyrate induces both cathelicidin mRNA and
      protein expression. Moreover, deletion or mutation of a putative activator
      protein-1 (AP-1) binding site in the cathelicidin gene promoter abrogated the
      response to sodium butyrate stimulation. Three different mitogen-activated
      protein (MAP) kinase inhibitors suppressed sodium butyrate-induced
      transactivation of the cathelicidin promoter. Electrophoretic mobility shift
      assays (EMSA) showed that nuclear extracts prepared from sodium butyrate
      stimulated EBC-1 cells generated specific binding to probe including a putative
      AP-1 binding site in the cathelicidin gene promoter. Furthermore, chromatin
      immunoprecipitation (ChIP) assays demonstrated that sodium butyrate augmented
      histone acetylation of the cathelicidin promoter in EBC-1 cells. Therefore, these
      results indicate that AP-1 and histone acetylation of the cathelicidin promoter
      play a critical role in the regulation of inducible cathelicidin gene expression
      in EBC-1 cells stimulated with sodium butyrate.

PMID- 16423399
TI  - The expression of membrane protein augments the specific responses induced by
      SARS-CoV nucleocapsid DNA immunization.
AB  - Nucleocapsid protein plays a critical role in SARS-CoV pathogenesis, and high
      level anti-nucleocapsid antibodies are detected in the patients infected by
      severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Several
      studies have shown that there exists an interaction between nucleocapsid (N) and
      membrane (M) protein. In this paper, we investigate whether the expression of
      membrane protein can affect the immune responses induced by nucleocapsid DNA
      immunization. Two recombinant plasmids containing M and N coding sequence were
      constructed. Moreover, in order to get the antigen for ELISA and in vitro
      stimulation assay, N protein were expressed and purified from E. coli bacteria.
      Injection of 20mug of the mixture of pVAX1-M and pVAX1-N into the Balb/c mice
      could elicit the humoral and cellular responses. The ELISA analysis using the N
      antigen or inactivated SARS-CoV particles as capture antigen showed that co
      injection of SARS-M could enhance N-induced antibody production, especially IgG2a
      subclass. After lymphocytes were stimulated with 10mug/ml purified N antigen, The
      CD4+ and CD8+ T cells of N and M plus N group were increased compared with those
      of control groups, and the M protein could augment the activation of lymphocytes
      induced by N DNA vaccine. Cytokine ELISA analysis revealed that co-injection of M
      could enhance the levels of IFN-gamma, IL-2 release induced by N antigen. Further
      experiments in field mouse also support the claim that membrane protein can
      augment the N-specific immune responses. Virus challenge test was conducted in
      BSL3 bio safety laboratory with Brandt's vole SARS-CoV model, and the results
      indicated that co-immunization of M and N antigens could reduce the mortality and
      pathological changes in lung from the virus infection.

PMID- 16423400
TI  - Major mountain cedar allergen, Jun a 1, contains conformational as well as linear
      IgE epitopes.
AB  - We have previously identified four linear IgE epitopes on Jun a 1, the dominant
      allergen in mountain cedar pollen, and mapped these to the surfaces of a
      molecular model and to the crystal structure of this glycoprotein. The aim of the
      present study was to determine if Jun a 1 also displays conformational IgE
      epitopes. Jun a 1 was denatured by heating at 75 degrees C for 1h, exposure to 6M
      guanidine or by reductive alkylation in the presence and absence of guanidine.
      The effects of these manipulations on the binding to IgE from patients with
      mountain cedar hypersensitivity was evaluated by an ImmunoCAP inhibition assay,
      using Jun a 1-specific caps. Treatment-associated changes in the 3D-structure
      were assessed by dynamic light scattering and CD spectroscopy. IgE binding to
      native Jun a 1 was inhibited 92+/-9% by soluble native protein and 92+/-9% by
      reduced and alkylated Jun a 1. However, the capacity of Jun a 1 to inhibit the
      binding of IgE antibodies was significantly diminished upon denaturation by heat,
      guanidine alone, or reduction and alkylation in guanidine, compared to native Jun
      a 1. Reductive alkylation treatment under denaturing conditions also increased
      the Stoke's radius, suggesting that the protein was partially unfolded. Analysis
      of the circular dichroism (CD) spectra suggested that heating and treatment with
      guanidine caused a loss of alpha-helical structure. Guanidine also caused an
      increase in random coil structure. Thus, at least a portion of the anti-Jun a 1
      IgE antibodies produced by allergic humans recognize conformational epitopes and
      it is likely that some of these epitopes reside in alpha-helical structures of
      Jun a 1.

PMID- 16423401
TI  - Distinct gene expression in human Vdelta1 and Vdelta2 gammadelta T cells
      following non-TCR agonist stimulation.
AB  - The two major human gammadelta T cell subsets, Vdelta1 and Vdelta2, display
      differences in tissue tropism and agonist responses, but we have little insight
      into global differences that may exist at the gene expression level. This is due
      to the small numbers of these cells that can be obtained from healthy donors,
      which limit comprehensive, comparative gene expression analyses. We established a
      culture method that expands Vdelta1 and Vdelta2 cells from the same PBL
      preparation to levels sufficient for sorting and microarray analysis. Although
      the subsets were expanded identically (anti-TCR mAb, plus IL-15), 392 and 614
      genes were identified, which were differentially expressed in the two subsets,
      from two donors, respectively. Approximately 4500 genes changed in both subsets
      following PMA/ionomycin treatment; about 50% of these genes were subset-specific.
      Both subsets responded to a crude LPS preparation, but only 6% of the responsive
      genes were the same. The differentially expressed genes were consistent with
      Vdelta2 cells being more inflammatory and Vdelta1 cells having more of a
      regulatory phenotype. Both subsets expressed transcripts encoding an array of
      innate and NK cell receptors, supporting the relationship of gammadeltaT cells to
      the innate immune system. Our results indicate that circulating Vdelta1 and
      Vdelta2 subsets in humans have considerable inherent differences in gene
      expression following treatment with the same agonist. The patterns of
      differentially expressed genes are consistent with unique functional roles for
      these cells in vivo.

PMID- 16423402
TI  - Effects of permethrin given before mating on the behavior of F1-generation in
      mice.
AB  - Permethrin, a type I synthetic pyrethroid insecticide, was evaluated through
      assessment of the behavioral development of F1 progeny of mice. Groups each of 30
      male and 30 female ICR (CD-1) mice, as F0-generation, were given 0, 4.9, 9.8, and
      19.6 mg/kg/d permethrin by gavage for 4 weeks before mating. Behavioral endpoints
      of motor reflexes, motor coordination, and activity were evaluated in F1 progeny.
      Clinical signs of toxicity including salivation, hyperactivity, and liquid feces
      which attributed to permethrin were observed in the F0-mice treated with 9.8 and
      19.6 mg/kg/d. Reduction of body weight became evident only during gestation and
      lactation periods for the middle and high dose groups. Significant differences in
      the development of reflexes, swimming ability, and open field activity were
      evident in the offspring for the 9.8 and 19.6 mg/kg/d dose groups compared to the
      control group. These results show that permethrin at dose levels of 9.8 and 19.6
      mg/kg/d can induce a significant risk to the offspring following treatment of F0
      mice before mating. The NOEL obtained in this study for the effects of permethrin
      on the development of the F1-progeny is 4.9 mg/kg/d.

PMID- 16423403
TI  - Al(III)-binding ability of an octapeptide and its phosphorylated derivative.
AB  - A synthetic octapeptide, H-GlyGluGlyGluGlySerGlyGly-OH, and its phosphorylated
      Ser derivative were synthetized and their solution speciation and binding modes
      in their complexes with Al(III) were measured. One goal of the work was find a
      lead compound for the design of a selective peptide-based Al(III) chelator. pH
      potentiometry was used to characterize the stoichiometry and the stability of the
      species formed in the interactions of the metal ion and the peptides, while
      multinuclear NMR was applied to characterize the binding sites of the metal ion
      in the complexes. CD spectroscopy revealed a difference in the conformational
      behaviour of the phosphorylated peptide as compared with its non-phosphorylated
      parent derivative. The Al(III) is presumed to enhance aggregation through the 
      PO3H(-)-Al(3+)-PO3(2-)-Al(3+)- intermolecular bindings between the peptide
      chains. The results of molecular dynamics calculations supported the
      experimentally obtained secondary structures and the binding position of Al(III).

PMID- 16423404
TI  - Pharmacological regulation of low density lipoprotein receptor expression:
      current status and future developments.
AB  - Plasma levels of low-density lipoprotein (LDL) cholesterol are considered to be a
      major risk factor for the development of cardiovascular diseases. The LDL
      receptor is the key component in the maintenance of cholesterol homeostasis in
      the body, playing a pivotal role by regulating the hepatic catabolism of LDL
      cholesterol. Many clinical studies using statins, which up-regulate the LDL
      receptor expression via a feedback mechanism, have demonstrated that the
      reduction of LDL cholesterol levels lowers the incidence of cardiovascular events
      in both primary and secondary prevention. In this context, new strategies
      designed to increase hepatic LDL receptor activity can be considered as
      attractive opportunities for future therapy. Several potential new drugs have
      been described in the last decade to up-regulate LDL receptor expression in vitro
      and in vivo, thus allowing the identification of new transcriptional and post
      transcriptional mechanisms.

PMID- 16423405
TI  - Determination of antibiotic residues and their interaction in milk with lactate
      biosensor.
AB  - Milk and dairy products are among the most important foodstuffs and the quality
      of raw milk is of significant importance from the point of view of human health.
      For rapid determination of chloramphenicol and penicillin residues in raw milk,
      lactate oxidase-based amperometric biosensor was used. The concentration of
      antibiotic residuals was determined by two characteristic reaction parameters,
      calculated from the biosensor transient response with the dynamic biosensor
      model. Both chloramphenicol and penicillin caused the decrease of the value of
      the kinetic parameter, but they changed the total signal change parameter in
      different ways. The shift of the combined total signal change parameter at the
      simultaneous presence of these antibiotics indicated their antagonistic effect.
      Due to the respiration process of bacteria in raw milk, the dynamics of the
      biosensor signal was different in warm and cold seasons. The respiration
      characteristics were added to the biosensor model as a negative linear time
      depending factor. The reaction characteristic parameters, obtained with this
      complemented model, showed excellent alignment in different conditions and
      allowed to detect antibiotic residues and their interaction in raw milk.

PMID- 16423406
TI  - Selective cultivation of N-cadherin expressing cells from the optic tectum of the
      chick.
AB  - Dissociated primary cell cultures of the nervous system are usually composed of
      many different cell types, which makes it difficult to investigate a specific
      cell type and to describe its development in vitro without direct or indirect
      influence of other cell types. Although various methods have been published to
      specifically separate either neurons or glial cells, there is still a need for
      simple protocols to isolate distinct neuronal subpopulations. Here we describe a
      method to purify specific neuronal subtypes from the chick embryonic midbrain.
      Embryonic (E10) optic tecta were dissociated and a cell suspension was produced.
      Cells were separated by magnetic cell sorting (MACS) based on their specific
      expression of somatic N-cadherin. After cultivation on poly-D-lysine coated
      dishes in serum-free culture medium supplemented with B27, cells were fixed and
      analyzed with immuncytochemistry. Enriched primary cultures contained about 70%
      of N-cadherin positive cells compared to 46% before sorting. 7 days after
      cultivation, N-cadherin expression and its co-localization with synapses was
      demonstrated.

PMID- 16423407
TI  - An improved post-operative care protocol allows detection of long-term functional
      deficits following MCAo surgery in rats.
AB  - Developing new therapeutants for stroke requires animal models in which typical
      stroke outcomes can be detected. In rats, temporary occlusion of the middle
      cerebral artery (MCAo) closely resembles reversible human ischemic stroke, but
      most neuroprotection studies have used limited, short-term (1-2 weeks)
      behavioural and histological endpoints in this model. Further, the use of this
      model for assessing long-term recovery has been questioned. Long-term deficits
      may be difficult to detect because testing may not reflect the diversity of
      functional outcomes in clinical stroke, and/or high mortality rates mean that
      only the least severely affected rats remain to be tested. We believe that
      enhanced survival through intensive post-operative husbandry practices, and
      extensive behavioural testing that reflects multiple clinically relevant
      behavioural endpoints, will permit the detection of long-term functional
      deficits. In the present study, male SD rats (280-320 g) received transient (90
      min) MCAo (n = 19) or sham surgery (n = 13). An intense post-operative care
      protocol was maintained, and assessments included various physical and
      sensorimotor parameters, tests of emotionality and tests of learning and memory.
      We report 0% mortality, and statistically significant deficits on all aspects of
      this battery, including learning and memory deficits up to 2 months post-MCAo.
      The current study demonstrates that with adequate post-operative care and
      extensive behavioural testing, assessing the potential of new therapeutants for
      promoting long-term functional neuroprotection following MCAo in the rat is
      feasible.

PMID- 16423408
TI  - Algorithmically designed peptides ameliorate behavioral defects in animal model
      of ADHD by an allosteric mechanism.
AB  - This study exemplifies the use of three ADHD-relevant methodological innovations.
      (1) The use of novel, patented, computational peptide design techniques to
      generate peptides targeting the extra-cellular and para-transmembrane amino acid
      loops of the putatively ADHD-involved, D(2) dopamine receptor, D(2)DAR; (2)
      experimental evidence that these peptides in L-amino acid/ortho ordered or D
      amino acid/reverse ordered (retro-inverso), D(2)DAR, hydrophobic eigenmode
      matched forms, evoked positive allosteric and indirect agonist influences on in
      vitro stably receptor transfected CHO and LtK cells and on in vivo, brain
      mediated activity; (3) a representative 15 residue all-D-amino acid, D(2) mode
      matched peptide, given parenterally, was found to "repair" a key aberrant ADHD
      behavioral characteristic in a standard animal model of ADHD, the Spontaneously
      Hypertensive Rat, SHR, relative to its progenitor species control, the Wistar
      Kyoto rat, WKY. The representative, retro-inverso peptide, all-D-LLYKNKPRYPKRNRE,
      reversed SHR's relative deficiency in sensory motor gating (pre-pulse inhibition,
      PPI) while leaving SHR's nonselective attention (rearings), impulsive behavior
      (time in center), and activity level (timed total motor behavior) unchanged.
      Amphetamine also reversed SHRs sensory gating defect, but with significant
      increases in nonselective attention, impulsivity and hyperactivity. These
      preliminary results suggest the possibility of a new, "softer" pharmacological
      approach to ADHD: hydrophobic mode matched peptide allosteric augmentation of the
      activity of indigenous dopamine with respect to D(2)DAR mediated function, in
      place of stimulant drug-induced presynaptic dopamine release or impairment of
      dopamine uptake.

PMID- 16423409
TI  - Competitive displacement binding assay on rat brain sections and using a beta
      imager: application to mu-opioid ligands.
AB  - A new approach of competitive displacement binding assay using brain sections and
      a beta-imager is presented to estimate binding parameters such as affinity and
      selectivity of new compounds or to characterize receptor families or subtypes of
      receptors in small brain regions. This method includes a preliminary saturation
      assay intended to define the optimal concentration of displaceable radio-labeled
      ligand followed by the determination of displacement constants (IC(50) and K(i))
      in cerebral regions rich in studied receptor. The technique application was
      demonstrated in seven rat brain structures, using displacement of the selective
      tritiated mu-opioid ligand [(3)H]-DAMGO by six opioid ligands: a specific agonist
      (DAMGO), less specific agonists (morphine, remifentanil), a non-specific
      antagonist with good affinity for mu receptors (naloxone) and ligands specific of
      other opioid subtypes (naltrindole, U50.488). Radioactivity counts were collected
      during 48 h. The assay-validation was performed by measuring intra- and inter
      assay variation on determinations and by comparing presently obtained K(i) values
      with data from recognised methodologies. Both prove the accuracy of the proposed
      method.

PMID- 16423410
TI  - Antiretroviral therapy-associated modulation of Th1 and Th2 immune responses in
      HIV-infected pregnant women.
AB  - A successful pregnancy is characterised by an increase in Th2 cytokines and
      suppression of Th1 cytokine production. A Th1 to Th2 cytokine shift is also
      observed in the disease progression of HIV infection. Highly active
      antiretroviral therapy (HAART) suppresses HIV viremia, increases CD4+ cell counts
      and counteracts the Th1 to Th2 shift. We hypothesised that the increased risk of
      premature delivery reported in HIV-infected, HAART-treated pregnant women is
      mediated through changes in the cytokine environment in pregnancy. Here, we
      present results relating to levels of interleukin (IL)-2 (Th1) and IL-10 (Th2) in
      peripheral blood mononuclear cells (PBMCs) measured three times during pregnancy
      in 49 HIV-infected women. Slope values representing the trend of repeated
      cytokine (IL-2-PHA, IL-2-Env, IL-10-PHA and IL-10-Env) measurements within women
      during pregnancy were estimated and median values compared by prematurity and
      HAART use. Multiple regression adjusted for HAART and cytokine slope clarified
      the additional and independent effect of HAART on prematurity risk. Results
      showed favourable immunomodulation induced by HAART with increased IL-2 and
      decreased IL-10. HAART use and IL-10-Env slopes were not significantly associated
      with prematurity risk, but each unit increase in IL-2-PHA slope was associated
      with an 8% increased risk of premature delivery (AOR, 1.08; 95% CI, 1.0-1.17;
      p=0.005). HAART use in pregnancy provides significant benefits in delaying HIV
      disease progression and reducing the risk of mother-to-child-transmission, but
      may be counterproductive in terms of successful pregnancy outcome.

PMID- 16423411
TI  - Family cohesion and children's behavior problems: a longitudinal investigation.
AB  - We examine the association of family cohesion and conflict with childhood
      behavior problems. A stratified random sample of 823 children was evaluated at
      ages 6 and 11 years. Mothers rated the family environment at age 6 using the
      Family Environment Scale. Mothers and teachers rated children's behavior problems
      at ages 6 and 11, using the Child Behavior Checklist and the Teacher Report Form,
      respectively. Multiple regression analysis, applying generalized estimating
      equations, was used. Although results varied between mothers' and teachers' data,
      they converged in identifying family cohesion as a factor in children's mental
      health. Family cohesion, as rated by mothers, had a beneficial effect on
      children's internalizing and attention problems, as rated by both mothers and
      teachers, that was stable over time. The study highlights an important
      relationship between family cohesion and children's internalizing and attention
      problems.

PMID- 16423412
TI  - Co-clustering activating and inhibitory receptors: impact at varying expression
      levels of the latter.
AB  - Clustering the mast cell function-associated antigen (MAFA) has earlier been
      shown to inhibit mast cells' secretory response to the type 1 Fcepsilon receptor
      (FcepsilonRI) stimulus. MAFA is a type II membrane glycoprotein first identified
      on rat mast cells and contains an immunoreceptor tyrosine-based inhibitory motif
      (ITIM) in its cytosolic domain. This inhibition is induced already upon
      clustering MAFA alone. Still, the inhibitory capacity of MAFA-FcepsilonRI co
      clustering has recently been characterized and co-clustered MAFA molecules were
      found to exhibit a markedly higher inhibition capacity than MAFA-clusters alone.
      We have now compared the inhibitory capacity of FcepsilonRI co-clustered MAFA on
      the secretory response of rat mucosal-type mast cells (RBL-2H3 line) expressing
      different levels of this inhibitory protein. Reacting these cells carrying an IgE
      class, 2,4 dinitrophenyl (DNP)-specific monoclonal antibody with DNP-conjugated
      F(ab')2 fragments of non-specific polyclonal mouse IgG causes clustering of the
      FcepsilonRI-IgE. Reaction of these cells with DNP-conjugated F(ab')2 fragments of
      the MAFA-specific, monoclonal antibody G63 co-aggregates MAFA together with the
      FcepsilonRI-IgE thereby producing FcepsilonRI-IgE-MAFA co-clusters. Results of
      measurements of the secretory responses of RBL-2H3 cells expressing higher or
      lower MAFA levels than those of unmodified cells provided further support to the
      notion that co-clustered MAFA molecules exhibit a markedly higher inhibition
      capacity than MAFA-clusters alone. The molecular basis for this enhanced
      inhibition is most probably the increased concentration of the inhibitory cell
      components in the immediate proximity of the co-clustered FcepsilonRI-MAFA.

PMID- 16423413
TI  - Development of an extraction and concentration procedure and comparison of RT-PCR
      primer systems for the detection of hepatitis A virus and norovirus GII in green
      onions.
AB  - Vegetables can be considered as a vector of transmission for human hepatic and
      enteric viruses such as hepatitis A virus (HAV) and noroviruses when contaminated
      by spoiled irrigation water or when prepared by infected food handlers. Recently,
      outbreaks of HAV have been reported in the USA involving fresh green onions. A
      viral elution-concentration method was developed for the detection of HAV and
      norovirus contaminated green onions by RT-PCR. Repeated pipetting/washings of the
      surface with a pH 9.5 glycine-buffered solution allowed the elution of viruses
      from the vegetables. Concentration of the viral load was performed by a
      polyethylene glycol (PEG) precipitation procedure. Viral RNAs were extracted and
      purified using a combination of Trizol-chloroform and poly(dT) magnetic beads
      methods. Different sets of primers, including two newly designed primers sets for
      HAV RT-PCR, were tested in order to achieve the best analytical sensitivity.
      Using the new primer design, it was possible to detect 10(0) TCID(50%)/25 g of
      HAV in fresh green onions, while 1 RT-PCRU/25 g was detected for noroviruses GII
      using previously described primers. This method, based on molecular tools, would
      be useful for diagnostic laboratories in order to perform viral analyses of such
      commodities as fresh vegetables in cases of foodborne infections.

PMID- 16423414
TI  - Establishment and characterization of a novel genetic hybrid cell line for
      propagation of four pathogens.
AB  - Chromosomal DNAs were purified from human epidermoid carcinoma (HEP-2) cells and
      transfected into human embryonic lung (HEL) cells to establish a genetic hybrid
      cell line susceptible to infections by toxoplasma, rubella virus,
      cytomegalovirus, and herpes simplex virus. Karyotype analysis showed that the
      resultant hybrid cells, designated D3, had a chromosome number of 96, which was
      stable after passage for 100 generations. Direct microscopy and
      immunofluorescence showed that the D3 cells could be infected by the four
      pathogens with overt cytopathic effects. The toxoplasma and three viruses were
      purified from infected D3 cells by sucrose gradient centrifugation and used as
      the antigens for detection of specific IgG and/or IgM in serum samples from
      pregnant women with suspicious infections by the four pathogens, the results of
      which were consistent with those of commercial kits. These data indicate that a
      stable genetic hybrid cell line has been generated, which is a valuable tool for
      the isolation of the four intrauterine pathogens and for the preparation of
      antigens for serological tests.

PMID- 16423415
TI  - Focal cerebral ischemia alters the spatio-temporal properties, but not the amount
      of activity in mice.
AB  - Cerebral ischemia induces sensorimotor and cognitive dysfunctions in rodents;
      however, little is known about the changes in the spatio-temporal organization of
      locomotor activity after ischemia. In this study, we continuously assessed the
      spatio-temporal properties of locomotor activity in an enclosure (40 cm x 40 cm x
      65 cm, arbitrarily divided into 16 zones) with feeding and drinking supplies, and
      observed the spatio-temporal changes in mice with focal cerebral ischemia.
      Locomotor tracks were recorded from 3rd to 24th h (total 22 h) after middle
      cerebral artery occlusion (MCAO) or sham operation. The absolute and relative
      distance traveled or time spent in different regions was analyzed. We found that
      there was no significant difference in total traveled distances over 22 h between
      the two groups. Control mice moved and stayed primarily in feeding and drinking
      zones, frequently in peripheral but rarely in central zones. However, ischemic
      mice lost such a property, almost evenly moved and stayed in 16 zones. Mice in
      both groups were more active (traveled more distances) shortly after they entered
      the enclosure, while ischemic mice returned to stable levels slower. The traveled
      distance had a remarkable circadian variation with more locomotion in the night
      in control mice, but not in ischemic mice. Most of the spatial parameters
      (ratios) of locomotor activity were closely correlated with the ischemic
      infarction, neuron densities (in cortex, hippocampal CA1 region and striatum),
      and typical behavioral assessments (neurological scores and inclined board test).
      Thus, these findings indicate that focal cerebral ischemia does not alter the
      amount of locomotor activity in mice, but impairs the spatio-temporal properties
      prolonging the initial hyperactivity and losing regionally special distribution
      of the activity.

PMID- 16423416
TI  - Left main coronary artery 'embolectomy' using a novel, straightforward technique.
AB  - A 60-year-old man experienced catastrophic haemodynamic decompensation 3 days
      following coronary artery bypass grafting (CABG). Aspiration thrombectomy to
      remove a left main coronary artery saddle embolus resulted in immediate
      haemodynamic improvement with no requirement for angioplasty or repeat bypass
      grafting. Coronary thromboembolism should be considered in the differential
      diagnosis of haemodynamic collapse post CABG. Urgent coronary angiography and
      aspiration thrombectomy may result in significant improvement for this condition.

PMID- 16423417
TI  - Simulation analyses to evaluate alternative control strategies for the 2002 foot
      and-mouth disease outbreak in the Republic of Korea.
AB  - Using the stochastic and spatial simulation model of between-farm spread of
      disease, InterSpread Plus, we evaluated the effect of alternative strategies for
      controlling the 2002 epidemic of foot-and-mouth disease (FMD) in the Republic of
      Korea. InterSpread Plus was parameterised to simulate epidemics of FMD in the
      population of farms containing susceptible animal species in the Korean counties
      of Yongin, Icheon, Pyongtaek, Anseong, Eumseong, Asan, Cheonan, and Jincheon. The
      starting point of our analyses was the simulation of a reference strategy, which
      approximated the real epidemic. The results of simulations of alternative
      epidemic-control strategies were compared with this reference strategy. Ring
      vaccination (when used with either limited or extended pre-emptive depopulation)
      reduced both the size and variability of the predicted number of infected farms.
      Reducing the time between disease incursion and commencement of controls had the
      greatest effect on reducing the predicted number of infected farms.

PMID- 16423418
TI  - The effect of sample size in studies of soil microbial community structure.
AB  - Replicate soil samples of 0.01, 0.1, 0.25, 1.0 and 10.0 g were taken from a
      single, large, homogenized sample from a field maintained as continuous meadow.
      The samples were processed for direct enumeration of bacterial cells and
      community structure assays by DGGE analysis of PCR-amplified 16S-rDNA fragments
      from whole community extracts. The goal was to determine the sample size or size
      range that produced the most consistent results (i.e., mean values) and the
      lowest variance. Enumeration data were analyzed by ANOVA, and the community
      composition fingerprints were analyzed by discriminant analysis (DA). Acceptable
      results were obtained for sample sizes from 0.1 to 1.0 g for both enumeration and
      community fingerprinting, but the size that yielded the best results for both
      measures was 0.25 g. The results suggest that for well homogenized silt loam
      soils with moderate organic matter concentrations, this sample size should
      produce high quality consistent results. For soils that differ in organic
      concentrations or clay content, a reconnaissance survey similar to the present
      examination is recommended.

PMID- 16423419
TI  - Potential of selected infant food formulas for production of Bacillus cereus
      emetic toxin, cereulide.
AB  - Cereulide producing Bacillus cereus was isolated from randomly chosen commercial
      infant foods. The cereulide production in infant food formulas was investigated.
      When the reconstituted foods were inoculated with >10(5) cfu ml(-1) of cereulide
      producing B. cereus, 2 to 200 microg of cereulide per 100 ml of food accumulated
      during 24 h of non-refrigerated storage. The amount of cereulide measured in the
      foods by the accurate chemical assay (LC-MS) matched with that found by sperm
      micro assay, proving the cereulide was the sole heat stable toxin in the foods
      and present in its toxic form. The infant formulas containing both cereal and
      dairy ingredients were the most supportive for cereulide production. Cereulide
      accumulation was affected by the infant food composition as well as by the
      handling of the food. Diluting the reconstituted food with water resulted in
      increased toxin production expressed as mug per volume. More cereulide was
      accumulated when the food was incubated stationary compared with moderate
      shaking. The amount of cereulide accumulated within 24 h at room temperature per
      100 ml of cereal and dairy or in rice-nondairy reconstituted infant formulas,
      inoculated with >or=10(5) cfu ml(-1) of B. cereus strain F4810/72, was higher or
      similar to the amounts reported for foods implicated in emetic type of food
      poisonings. Thus mishandling and temperature abuse of infant foods may cause food
      poisoning when emetic B. cereus is present.

PMID- 16423420
TI  - Validation of an optical sensor-based high-throughput bioreactor system for
      mammalian cell culture.
AB  - Cell culture optimization is a labor-intensive process requiring a large number
      of experiments to be conducted under varying conditions. Here we describe a high
      throughput bioreactor system that allows 12 mini stirred-tank bioreactors to be
      operated simultaneously. All bioreactors are monitored by low-cost minimally
      invasive optical sensors for pH and dissolved oxygen. The sensors consist of
      single-use patches affixed inside the bioreactors and monitored optically from
      the outside. Experimental results show that different sensing patches with the
      same composition respond consistently. The discrepancy between different pH
      sensors is less than 0.1 pH units over most of their responsive range. The
      discrepancy between different dissolved oxygen sensors is less than 10% over the
      whole range from 0% to 100% dissolved oxygen. The consistency of the sensing
      system ensures that only an initial one-time calibration is required for the
      sensing patches. After that, a calibration code is generated and sensing patches
      of the same composition can be used directly. This greatly reduces the time and
      cost required for monitored multi-bioreactor operations. We used SP2/0
      myeloma/mouse hybridoma cell cultures to demonstrate reactor performance
      consistency. Transcriptional profiling, HPLC analysis, viable cell count, and
      viability inspection show that the presence of sensing patches and the use of
      optical monitoring have no apparent effect on the metabolism of the cells.

PMID- 16423421
TI  - EsiRNAs inhibit Hepatitis B virus replication in mice model more efficiently than
      synthesized siRNAs.
AB  - RNA interference (RNAi) has been proved to be a promising strategy to combat
      Hepatitis B virus (HBV) infection by way of cell culture and animal model
      studies. In this work, esiRNAs (endoribonuclease-prepared siRNAs) targeting all
      of the four open reading frames (ORFs) of HBV genome were prepared. In vitro
      experiment showed that esiHBVP suppressed HBsAg expression most effectively. Its
      capacity to suppress HBV replication in vivo was then tested. A single dose of 1
      microg esiHBVP was able to reduce HBsAg and HBeAg level in the mouse serum by 90
      and 89% one day after injection, while the same amount of chemically synthesized
      siRNA only reduced that by 33 and 45%. Immunostaining of HBcAg showed that
      esiHBVP inhibited HBcAg expression more potently than chemically synthesized
      siRNA. Quantification of HBV DNA in the mouse serum showed 1 microg eiHBVP
      treatment reduced serum HBV DNA copy number to 18% that of the untreated control,
      while 1 microg siRNA treatment only reduced that to 63%. In conclusion, the data
      presented here proved that esiRNA is much more efficient in suppressing HBV
      replication than chemically synthesized siRNA, and it might be a better
      therapeutic agent to fight against HBV infection.

PMID- 16423423
TI  - n-gram-based classification and unsupervised hierarchical clustering of genome
      sequences.
AB  - In this paper we address the problem of automated classification of isolates,
      i.e., the problem of determining the family of genomes to which a given genome
      belongs. Additionally, we address the problem of automated unsupervised
      hierarchical clustering of isolates according only to their statistical substring
      properties. For both of these problems we present novel algorithms based on
      nucleotide n-grams, with no required preprocessing steps such as sequence
      alignment. Results obtained experimentally are very positive and suggest that the
      proposed techniques can be successfully used in a variety of related problems.
      The reported experiments demonstrate better performance than some of the state-of
      the-art methods. We report on a new distance measure between n-gram profiles,
      which shows superior performance compared to many other measures, including
      commonly used Euclidean distance.

PMID- 16423422
TI  - A peptide competing with VEGF165 binding on neuropilin-1 mediates targeting of a
      chlorin-type photosensitizer and potentiates its photodynamic activity in human
      endothelial cells.
AB  - Destruction of the neovasculature is essential for efficient tumor eradication by
      photodynamic therapy (PDT). Since the over-expression of receptors for vascular
      endothelial growth factor (VEGF) is correlated with tumor angiogenesis and
      subsequent growth, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20
      triphenyl-chlorin, TPC), via a spacer (6-aminohexanoic acid, Ahx), to a VEGF
      receptor-specific heptapeptide (ATWLPPR). ATWLPPR and TPC-Ahx-ATWLPPR bound
      exclusively to neuropilin-1 (NRP-1) recombinant chimeric protein (IC50=19 and 171
      microM, respectively) but were devoid of affinity for VEGF receptor type 2 (VEGFR
      2, KDR), to which ATWLPPR was initially thought to bind. TPC-Ahx-ATWLPPR was
      incorporated up to 25-fold more in human umbilical vein endothelial cells (HUVEC)
      than TPC over a 24-h period, and the addition of 8 mM ATWLPPR induced a
      significant decrease of this uptake (P<0.05), corroborating a receptor-mediated
      incorporation. Slightly less cytotoxic in the dark, TPC-Ahx-ATWLPPR exhibited
      enhanced in vitro photodynamic activity (10.4-fold), compared to TPC.
      Pharmacokinetic analysis in nude mice xenografted with U87 human malignant glioma
      cells revealed relevant tumor levels as soon as 1 h after intravenous injection
      of TPC-Ahx-ATWLPPR, and a rapid elimination from the blood compartment. Moreover,
      TPC-Ahx-ATWLPPR was not degraded in vivo up to 2 h after intravenous injection.
      Taken together, our results demonstrate that TPC-Ahx-ATWLPPR is a much more
      potent photosensitizer in vitro than TPC, in NRP-1-expressing cells. Thus, it may
      efficiently potentiate the vascular effect of PDT in vivo.

PMID- 16423424
TI  - Techniques for biased data distributions and variable classification with neural
      networks applied to otoneurological data.
AB  - It is frequently useful and advantageous to investigate not only the
      classification efficacy of neural networks, but also the reasons for
      misclassification and relations between input variables and output classes. We
      have developed novel techniques to disentangle these dilemmas: a network
      structure and learning strategy for biased output class distributions, a method
      to measure the classification information incorporated in variables and variable
      groups, and methods to express properties learned by a network from its
      structure. We tested these techniques with otoneurological data from the
      conjunction with vertiginous diseases that we have explored in our previous
      neural network studies.

PMID- 16423425
TI  - Robust segmentation and analysis of DNA microarray spots using an adaptative
      split and merge algorithm.
AB  - Microarray images push to their limits classical analysis methods, since gene
      spots are often poorly contrasted, ill defined and of irregular shapes. These
      characteristics hinder a robust quantification of corresponding values for red
      and green intensities as well as their R/G ratio. New approaches are thus needed
      to ensure accurate data extraction from these images. Herein we present an
      automatic non-supervised algorithm for a fast and accurate spot data extraction
      from DNA microarrays. The method is based on a split and merge algorithm, relying
      on a Delaunay triangulation process, allowing an incremental partition of the
      image into homogeneous polygons. Geometric properties of triangles as well as
      homogeneity criteria are defined according to the specificities of microarray
      image signals. The method is first assessed on simulated data, and then compared
      with GenePix and Jaguar Softwares. Results in segmentation and quantification are
      superior to those obtained from a number of standard techniques for spot
      extraction.

PMID- 16423426
TI  - Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer.
      Relation to clinicopathological factors, beta-catenin and prognosis.
AB  - Matrix metalloproteinases (MMPs) have been shown to have a significant role in
      determining cancer cell behaviour. The present study was undertaken to analyze
      the expression and prognostic value of MMP-7 and MMP-9 in non-small cell lung
      cancer (NSCLC). The relationship of MMP-7 with beta-catenin was also evaluated.
      The study consists of 212 patients with resected NSCLC. Tumour samples were
      stained immunohistochemically, and the expression of MMP-7 and MMP-9 was
      evaluated in both tumour cells and peritumoural stromal tissue. The results were
      compared to clinicopathological factors of the patients. A high staining of MMP-7
      and MMP-9 in tumour cells was noted in 62 (30%) and 113 (57%) cases,
      respectively. Expression of MMP-7 was noted more often in adenocarcinomas than in
      other histological types (p=0.022). High cancer cell associated MMP-7 was related
      to lower T-factor (p=0.037), better tumour differentiation (p=0.005) and normal
      beta-catenin expression in tumour cells (p=0.001). A high MMP-9 expression in
      tumour cells was related to poor tumour differentiation (p=0.016). The stromal
      signal for MMP-9 was observed in 58 (32%) cases and was linked with higher tumour
      grade (p=0.031). In survival analyses the significant predictors of survival were
      histological type of tumour and tumour stage (p=0.0009 and 0.0012, respectively).
      MMP-7 or MMP-9 signals were not related to patient's outcome. The results show
      that high MMP-9 expression indicates aggressive, and high MMP-7 less aggressive
      tumour behaviour in NSCLC. However, MMP-7 and MMP-9 expressions had no prognostic
      value in NSCLC.

PMID- 16423427
TI  - Epigenetic modulation of the developing serotonergic neurotransmission in the
      semi-precocial rodent Octodon degus.
AB  - Environmental influences during early life periods, particularly those provided
      by the mother or parents, are generally considered to have a strong impact on the
      development of brain and behaviour of the offspring. In the semi-precocial South
      American species Octodon degus, a rodent becoming increasingly popular in
      different laboratory research fields, the present study aimed to examine the
      consequences of the disturbance of the parent-offspring interaction induced by
      parental separation on the serotonergic neurotransmission. Based on a
      quantitative neurochemical approach using brain homogenates obtained from
      cortical regions and the hippocampus our results revealed that (i) the tissue
      levels of serotonin and 5-hydroxyindoleacetic acid showed in both sexes a
      moderate, around two-fold increase until adulthood, indicating relatively matured
      cortical and hippocampal serotonergic systems at birth. In addition, we found an
      age-, region- and sex-specific pattern of changes in the serotonergic system
      induced by (ii) an acute stress challenge early in life (1-h parental separation
      at the postnatal day 3, 8, 14 or 21) with the most pronounced effects at earlier
      ages (between postnatal days 3 and 14) in the female cortex and (iii) repeated
      stress exposure (1h daily) during the first 3 weeks of life affecting cortical
      regions of both sexes. Taken together, these data indicate that early life stress
      (i.e. parental separation) influences the developing serotonergic system in the
      semi-precocial O. degus, even if the brain is relatively well matured at the
      early stages of postnatal development.

PMID- 16423428
TI  - Non-invasive imaging of neuropathology in a rat model of alpha-synuclein
      overexpression.
AB  - Parkinson's disease is a neurodegenerative disorder affecting the dopaminergic
      neurons in the substantia nigra. Aggregation of alpha-synuclein appears to play a
      central role in the pathogenesis. Novel animal models for neurodegeneration have
      been generated by lentiviral vector-mediated locoregional overexpression of
      disease-associated genes in the adult brain. We have used lentiviral vectors to
      overexpress a clinical mutant of alpha-synuclein, A30P, in the rat substantia
      nigra. This overexpression induced time-dependent cytoplasmic and neuritic
      accumulation of alpha-synuclein and neurodegeneration. A subgroup of the rats
      developed asymmetric rotational behavior after administration of amphetamine. In
      addition, these animals displayed reduced dopamine transporter binding visualized
      by 123I-FP-CIT microSPECT imaging. The behavioral and microSPECT data were
      validated by histological analysis. There was a strong correlation between the
      reduction of dopaminergic neurons in the substantia nigra and the reduction of
      dopamine transporter binding in the striatum. MicroSPECT imaging enables non
      invasive imaging of the neurodegeneration allowing longitudinal follow-up in this
      new animal model for Parkinson's disease and the evaluation of neuroprotective
      drugs.

PMID- 16423429
TI  - Serological response to pneumococcal vaccination in HAART-treated HIV-infected
      patients: one year follow-up study.
AB  - The aim of this study was to evaluate specific IgG responses against pneumococcal
      serotypes 1, 6B, 14, 19F, 23F at baseline, 1 and 12 months after vaccination with
      the 23-valent polysaccharide pneumococcal vaccine in 89 HAART-treated HIV
      infected patients, 24 antiretroviral "naive" HIV-infected and 30 non-HIV-infected
      healthy subjects. Levels of specific antipneumococcal IgG and the mean fold
      increase in IgG levels at 1 month as well as the kinetics of antibodies along the
      12 months in all groups of HIV-infected patients and healthy subjects were
      similar. Neither CD4 cell count at baseline nor "nadir" CD4 cells correlated with
      the response to the vaccine. In conclusion, the immunogenicity conferred by the
      polysaccharide vaccine in HIV-infected patients under HAART is at least as good
      as that observed in healthy subjects.

PMID- 16423430
TI  - Vaccination with a preparation based on recombinant cysteine peptidases and
      canine IL-12 does not protect dogs from infection with Leishmania infantum.
AB  - Cysteine peptidases (CPs) have been implicated in various processes central to
      the pathogenicity of Leishmania parasites, and are thought to be key factors in
      the host-parasite interaction. In order to fully evaluate the potential of the
      CPs as vaccine candidates, studies in natural host species are required. In the
      study we report here, recombinant L. infantum CPs CPA and CPB were used to
      vaccinate dogs. In order to induce an appropriate response against the antigens,
      recombinant canine IL-12 was added as an adjuvant either by itself or in
      combination with Quil A. After vaccination, dogs were given an intravenous
      challenge with promastigotes of L. infantum JPC strain. In both vaccinated groups
      (CPs with IL-12 or CPs with IL-12 and Quil A) CP-specific antibodies were
      detected after vaccination, indicating that there was a reaction to the vaccine.
      However, all dogs were found parasite-positive and all developed some degree of
      clinical leishmaniosis. The observed lack of efficacy of the candidate vaccines
      could be due, completely or in part, to a number of factors associated with the
      vaccine antigen, the adjuvant or host-parasite interactions. When compared to
      results from other studies, it seems less likely that the molecular conformation
      of the rCPs or rIL-12 caused this lack of efficacy. More plausible explanations
      are the dose and timing of the IL-12 application and the potentially different
      effects IL-12 induces as an adjuvant in either the murine or the canine
      leishmaniosis model.

PMID- 16423431
TI  - Protective immunization against "Candidatus Helicobacter suis" with heterologous
      antigens of H. pylori and H. felis.
AB  - "Helicobacter (H.) heilmannii" type 1 colonizes the human stomach. It has been
      shown to be identical to "Candidatus H. suis", a Helicobacter species colonizing
      the stomach of more than 60% of slaughter pigs. This bacterium is, until now, not
      isolated in vitro. The effect of vaccination on "Candidatus H. suis" infection
      was studied in a mouse model. Mice were vaccinated intranasally or subcutaneously
      with whole bacterial cell lysate of Helicobacter pylori or Helicobacter felis and
      subsequently challenge infected with "Candidatus H. suis". Intranasal and
      subcutaneous immunisation caused a decrease in faecal excretion of "Candidatus H.
      suis" DNA. Urease tests on stomach tissue samples at 16 weeks after challenge
      infection were negative in all H. felis intranasally immunized animals and in the
      majority of the animals of the other immunisation groups. Since PCR on stomach
      tissue samples at 16 weeks after challenge infection could still detect
      "Candidatus H. suis DNA" in all immunisation-challenge groups, complete clearance
      of challenge bacteria was not achieved.

PMID- 16423432
TI  - Potential cost-effectiveness of annual influenza immunization for infants and
      toddlers: experience from Canada.
AB  - BACKGROUND: In 2004, expert groups in North America recommended annual influenza
      immunization for healthy infants and toddlers aged 6-23 months with a goal of
      reducing high hospitalization rates (HR). We assess cost-effectiveness of this
      program in Canada. METHODS: Analysis was from third-party payer and societal
      perspectives in preventing hospitalization and other outcomes among 500,000
      vaccinated or non-vaccinated infants/toddlers. Base-case assumptions include: 25%
      attack rate (AR), 1% case hospitalization rate (HR), 0.002% case fatality,
      vaccine effectiveness (VE) of 66%, CDN dollar 15 per dose for vaccine and
      administration, half of mothers requiring 2h from work per dose to immunize and
      two doses required by 100% (first year) or 33% (subsequent years) of
      infants/toddlers immunized. RESULTS: After the first year, infant/toddler
      influenza immunization costs the third-party approximately CDN dollar 9 per day
      of illness averted, CDN dollar 120 per physician visit averted, CDN dollar 7000
      per hospitalization averted, CDN dollar 3 million per death averted and CDN
      dollar 450,000 per life year gained. Corresponding costs from societal
      perspective are approximately CDN dollar 3, CDN dollar 45, CDN dollar 2500, CDN
      dollar 1 million and CDN dollar 170,000. The program becomes cost-saving from the
      third-party perspective at AR>55%, HR>4%, or cost per dose (for vaccine and its
      administration) <CDN dollar 6.81. From the societal perspective corresponding
      break-even occurs at 28%, 2% and CDN dollar 11.90, or when half of all mothers
      require no more than 1.6h to immunize or VE is >74%. CONCLUSIONS: In the base
      case, infant/toddler influenza immunization is not cost-saving but could become
      more cost-effective in settings of higher attack rate and lower immunization
      cost. In this context, immunization of children in daycare or other group
      settings should be preferentially considered. Economic analyses should routinely
      inform expansions to influenza immunization programs.

PMID- 16423433
TI  - Endoscopically assisted reduction and fixation of condylar neck/base fractures-
      The learning curve.
AB  - Following the introduction of a new technique for fixation of fractures of the
      condylar neck and base in our department, the operative times were compared with
      those for the traditional and frequently used method of open reduction and
      internal fixation. A distinct learning curve was seen.

PMID- 16423434
TI  - Immediate mechanical stability of sagittal split ramus osteotomy fixed with
      resorbable compared with titanium bicortical screws in mandibles of sheep.
AB  - Ten fresh mandibles from adult sheep were stripped of all soft tissues and
      sectioned in the midline. We did sagittal split osteotomies and 5 mm advancement
      on all the 20 hemimandibles. Ten hemimandibles were fixed with three 2.0 mm x 13
      mm titanium bicortical screws, and the other 10 were fixed with three 2.0 mm x 13
      mm poly-l-lactic acid/polyglycolic acid (PLLA/PGA) bicortical screws in an
      inverted L pattern. All the hemimandibles were then mounted in a servohydraulic
      testing unit and tested to permanent deformation. Maximum forces that the
      mandibles resisted before breaking, maximum displacements, and the displacement
      values under 20, 60, 120, and 150 N were compared using the Mann-Whitney U-test.
      There were no significant differences in stability between the bones fixed with
      titanium and those fixed with resorbable screws.

PMID- 16423435
TI  - Public and private domains of religiosity and adolescent smoking transitions.
AB  - We used data from a nationally representative sample of US adolescents in school
      grades 7 through 12 to explore the effects of public and private religiosity on
      initiation, escalation, and cessation of smoking. We found that adolescents'
      decisions to experiment with smoking are influenced by both their individual
      practice of their faith and by participation in a larger faith community.
      However, the effects of private and public religiosity are specific to different
      decision points on the smoking uptake process. Private religiosity was protective
      against initiation of regular smoking among nonsmokers. It also was protective
      against initiation of experimental smoking but only when the young person
      frequently attended religious services or a religious youth group. Although
      private religiosity appeared to discourage the uptake of smoking, it was
      unrelated to reduction or cessation once a young person has become addicted to
      cigarettes. In contrast, public religiosity did predict reduction and cessation
      of cigarette use among regular smokers. Taken together, these findings
      demonstrate that the domains in which religiosity are important extend beyond the
      individual and include religious institutions.

PMID- 16423437
TI  - Before and after the 1999 Chi-Chi earthquake: traumatic events and depressive
      symptoms in an older population.
AB  - Natural disasters, such as earthquakes, can have deleterious consequences for
      physical and psychological health. In this study, we investigate variability in
      resilience to depressive symptoms in the aftermath of a massive earthquake that
      struck Taiwan in 1999. We analyze data on 1160 older individuals from a national,
      longitudinal survey with interviews before and after the earthquake. This survey
      contains extensive information on physical and cognitive function, depressive
      symptoms, socio-demographic characteristics and earthquake-related exposure and
      experiences. We estimate regression models to identify risk factors associated
      with the presence of depressive symptoms after the disaster, controlling for
      health status and the presence of depressive symptoms beforehand. We pay special
      attention to how socio-demographic factors moderate the psychological impact of
      the earthquake. Results indicate that persons of low socioeconomic status (SES),
      socially isolated individuals, and women reported higher levels of depressive
      symptoms than their respective counterparts, as did persons who experienced
      damage to their homes. The psychological effects of damage were strongest among
      those aged 54-70. The findings suggest that people who experience damage to their
      home during a disaster are at risk of experiencing depressive symptoms, with the
      elderly being more resilient than the near-elderly.

PMID- 16423436
TI  - Alcohol outlets, gonorrhea, and the Los Angeles civil unrest: a longitudinal
      analysis.
AB  - This study tests the effect of neighborhood changes on gonorrhea rates. Prior
      studies that indicate gonorrhea rates are associated with alcohol outlet density
      and neighborhood deterioration have been cross-sectional and cannot establish
      causality. After the 1992 Civil Unrest in Los Angeles, 270 alcohol outlets
      surrendered their licenses due to arson and vandalism thus providing a natural
      experiment. We geocoded all reported gonorrhea cases from 1988 to 1996 in LA
      County, all annually licensed alcohol outlets, and all properties damaged as a
      result of the civil unrest. We ran individual growth models to examine the
      independent effects of changes in alcohol outlets and damaged buildings on
      gonorrhea. The individual growth model explained over 90% of the residual
      variance in census tract gonorrhea rates. After the civil unrest, a unit decrease
      in the number of alcohol outlets per mile of roadway was associated with 21 fewer
      gonorrhea cases per 100,000 (p<.01) in tracts affected by the Unrest compared to
      those not affected. Neighborhood alcohol outlets appear to be significantly
      associated with changes in gonorrhea rates. The findings suggest that efforts to
      control sexually transmitted diseases, including gonorrhea and HIV, should
      address contextual factors that facilitate high-risk behaviors and disease
      transmission.

PMID- 16423438
TI  - Episodic representations support early semantic learning: evidence from midazolam
      induced amnesia.
AB  - Current controversy exists regarding the role of episodic representations in the
      formation of long-term semantic memories. Using the drug midazolam to induce
      temporary amnesia we tested participants' memories for newly learned facts in a
      semantic cue condition or an episodic and semantic cue condition. Following
      midazolam administration, memory performance was superior in the episodic and
      semantic condition, suggesting early semantic learning is supported by episodic
      representations.

PMID- 16423439
TI  - Using perfusion fMRI to measure continuous changes in neural activity with
      learning.
AB  - In this study, we examine the suitability of a relatively new imaging technique,
      arterial spin labeled perfusion imaging, for the study of continuous, gradual
      changes in neural activity. Unlike BOLD imaging, the perfusion signal is stable
      over long time-scales, allowing for accurate assessment of continuous
      performance. In addition, perfusion fMRI provides an absolute measure of blood
      flow so signal changes can be interpreted without reference to a baseline. The
      task we used was the serial response time task, a sequence learning task. Our
      results show reliable correlations between performance improvements and decreases
      in blood flow in premotor cortex and the inferior parietal lobe, supporting the
      model that learning procedures that increase efficiency of processing will be
      reflected in lower metabolic needs in tissues that support such processes. More
      generally, our results show that perfusion fMRI may be applied to the study of
      mental operations that produce gradual changes in neural activity.

PMID- 16423440
TI  - The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in
      Japanese psychiatric patients.
AB  - The authors investigated the impact of the CYP2D6 genotypes on the plasma
      concentration of paroxetine (PAX) in 55 Japanese psychiatric patients. They were
      administered 10 to 40 mg/day (24+/-10.0 mg/day) of PAX and maintained at the same
      daily dose for at least two weeks to obtain the steady-state concentrations. The
      plasma levels of PAX were 15.8+/-15.0, 47.4+/-32.0, 101.2+/-59.9 and 177.5+/
      123.6 ng/ml at the daily dose of 10, 20, 30 and 40 mg, respectively, which
      suggested dose dependent kinetics of PAX. The allele frequencies of the CYP2D65,
      CYP2D610 and CYP2D641 were 1.8%, 41.8% and 1.8%, respectively. Significantly
      higher PAX concentrations were observed in the patients having one functional
      allele compared with those with two functional alleles (150.9+/-20.6 vs. 243.6+/
      25.2 ng/ml mg(-1) kg(-1), p<0.05, Newman-Keuls multiple comparison test) or no
      functional (243.6+/-25.2 vs. 76.7+/-6.1 ng/ml mg(-1) kg(-1), p<0.05, Newman-Keuls
      multiple comparison test) in the subjects with 30 mg/day of paroxetine. The same
      trend of findings as in the subjects treated with 30 mg/day were observed in the
      subjects with 40 mg/day of PAX. The present results suggest that having one non
      functional allele is the marker for high plasma concentration of PAX when
      relatively high daily dose of PAX is administered.

PMID- 16423441
TI  - Validation of a model to evaluate the role of radiographs in the diagnosis and
      treatment planning of periodontal diseases.
AB  - OBJECTIVES: The purposes of this study were (i) to see if an indirect method of
      design (paper patients) could be developed for study of change affected by
      radiographs on diagnostic outcome and planned treatment of periodontal patients
      and (ii) to investigate the effect of the nature of clinical examination on the
      value of radiographs in reaching a periodontal diagnosis. Paper cases could allow
      the design of examiner blind studies where repeatability could be assessed.
      METHODS: 201 patients were assigned to one of four groups and clinically assessed
      according to group specifications. Radiographs were taken. Periodontal diagnoses
      and treatment plans were drawn up for each patient with and without radiographic
      information (real patient). Simulated paper transcriptions were made for each
      subject and diagnoses and treatment plans were again drawn up (paper patient).
      RESULTS: For many diagnoses and treatment options assessments were similar for
      real and paper patients. There was substantial agreement between periodontal
      diagnoses reached from real and paper assessments (kappa=0.68). Greater
      differences were seen for extractions and periodontal surgery. Paper assessments
      better replicated real assessments when more thorough clinical examinations were
      undertaken. The relatively time efficient Group 2 clinical assessment appeared to
      perform similarly to the extensive Group 4 clinical assessment. CONCLUSIONS: The
      model described may be useful for simulating real patients for studies of this
      nature. The Group 2 assessment appeared to give sufficient clinical information
      for patient management and may be an appropriate choice for initial diagnosis and
      treatment planning of periodontal patients.

PMID- 16423442
TI  - Induction and expression mechanisms of postsynaptic NMDA receptor-independent
      homosynaptic long-term depression.
AB  - The induction of long-term depression (LTD) can be divided into two main forms,
      one dependent upon activation of postsynaptic NMDAR, and another independent of
      postsynaptic NMDAR. Non-postsynaptic NMDAR-LTD (non-NMDAR-LTD) occurs in many
      regions of the brain, and encompasses a wide variety of induction and expression
      mechanisms. In this article, the induction and expression mechanisms of such LTD
      in over 10 brain regions are described, with a number of common mechanisms
      compared across a large range of types of LTD. The article describes the
      involvement of different presynaptic or postsynaptic receptors in the induction
      of non-NMDAR-LTD, especially metabotropic glutamate receptors, cannabinoid
      receptors and dopamine receptors. An increase in presynaptic or postsynaptic
      intracellular Ca concentration is a key event in induction, commonly followed by
      activation of certain kinases, especially PKC, p38 MAPK and ERK. Expression
      mechanisms are either presynaptic via a reduction in release probability, or
      postsynaptic involving a decrease in AMPAR via phosphorylation of a glutamate
      receptor subunit, especially GluR2, followed by clathrin-mediated endocytosis.
      Retrograde signalling from postsynaptic to presynaptic occurs when induction is
      postsynaptic and expression is presynaptic.

PMID- 16423443
TI  - Obstetric complications, genetics and psychosis.

PMID- 16423444
TI  - Placental site trophoblastic tumor originating in a tubal ectopic pregnancy.

PMID- 16423445
TI  - Elective abortions for minors: impact of the new law in France.
AB  - OBJECTIVE: This study in a French family planning centre assessed the impact of
      the new law (July 2001) concerning minors seeking elective abortions. STUDY
      DESIGN: We compared two historical cohorts of adolescents (<18 years). The
      "before" (n=61) and "after" (n=81) cohorts comprise the patients seen for the
      year before and the year after the effective date of the new statute. The data
      came from medical records. We compared the girls' obstetrical history and their
      social, demographic and medical characteristics. RESULTS: Obstetrical history did
      not differ significantly between the two cohorts (p>0.05), nor did most of the
      social and demographic characteristics. Fewer adolescents in the "before" (29.5%)
      than in the "after" (51.2%) (p<0.05) cohort did not use contraceptives. There
      were no significant differences between the two study periods for the adult
      selected to accompany the minor or for the reasons given for refusing to inform a
      parent. In the "before" cohort, the girl's legal representative always provided
      consent, while only 63% did so in the "after" cohort. CONCLUSION: The scope of
      application of the new law substantially exceeded the legislative intent, since
      recourse to non-parental adults was not rare, even though the reasons for not
      informing parents did not differ during the two study periods.

PMID- 16423447
TI  - Scalability of the surface-based DNA algorithm for 3-SAT.
AB  - Since Adleman first proposed DNA computing for the Hamiltonian path problem,
      several authors have reported DNA computing for 3-SAT. Previous research
      presented DNA computing on surfaces and demonstrated how to solve a four-variable
      four-clause instance of 3-SAT, and claimed that the surface-based approach was
      designed to scale up to larger problems. In this paper we establish an error
      model for the incomplete "mark" and imperfect "destroy" operations. By using the
      error model we argue that no matter how large the "mark" and "destroy" rates are
      we can always give satisfiable instances of 3-SAT such that no DNA strands remain
      on the surface at the end of the computation. By the surface-based approach the
      satisfiable instances of 3-SAT would be misdetermined to be unsatisfiable. Thus,
      the error leads to an incorrect result of the SAT computation. Furthermore, given
      the "mark" rate p and the "not-destroy" rate rho, we find that the approach can
      only solve at most N-variable instances of 3-SAT problems, where
      N=[(2+beta(2)+2+2 square root beta (2))/beta(2)] in which beta=1-1/(p+rhoq) and
      q=1-p and [a] is the greatest integer less than a or equal to a.

PMID- 16423446
TI  - Pre-treatment nomogram for disease-specific survival of patients with
      chemotherapy-naive androgen independent prostate cancer.
AB  - OBJECTIVE: Our objective was to develop a nomogram that predicts the probability
      of cancer-specific survival in men with untreated androgen-independent prostate
      cancer (AIPC). METHODS: AIPC was diagnosed in 129 consecutive patients between
      1989 and 2002. No patient received cytotoxic chemotherapy. Univariate and
      multivariate Cox regression models were used to test the association between
      prostate-specific antigen (PSA) level at initiation of androgen deprivation, PSA
      doubling time (PSADT), PSA nadir on androgen deprivation therapy (ADT), time from
      ADT to AIPC, and AIPC-specific mortality. Multivariate regression coefficients
      were then used to develop a nomogram predicting AIPC-specific survival at 12-60
      mo after AIPC diagnosis. Two-hundred bootstrap resamples were used to internally
      validate the nomogram. RESULTS: AIPC-specific mortality was recorded in 74 of 129
      patients (57.4%). Other-cause mortality was recorded in 7 men (5.4%). Median
      overall survival was 52.0 mo (mean, 36.0 mo) and median AIPC-specific survival
      was 54.0 mo (mean, 35.0 mo). In univariate regression models, all variables were
      significant predictors of AIPC-specific survival (p < or = 0.02). In multivariate
      models, PSADT and time from androgen deprivation to AIPC remained statistically
      significant (p < or = 0.004). Bootstrap-corrected predictive accuracy of the
      nomogram was 80.9% versus 74.9% for our previous model. CONCLUSIONS: A nomogram
      predicting AIPC-specific survival is between 13% and 14% more accurate than
      previous nomograms and 6% more accurate than tree regression-based predictions
      obtained from the same data. Moreover, a nomogram approach combines several
      advantages, such as user-friendly interface and precise estimation of individual
      recurrence probability at several time points after AIPC diagnosis, which all
      patients deserve to know and all treating physicians need to know.

PMID- 16423448
TI  - Membrane estrogen receptors: genomic actions and post transcriptional regulation.
AB  - The primary cellular location of the nuclear estrogen receptor II (nER II) is the
      plasma membrane. A number of reports that have appeared in the recent past
      indicate that plasma membrane localized estrogen receptor alpha (ERalpha) also
      exists. Whether the membrane localized ERalpha represents the receptor that binds
      to the estrogen responsive element (ERE) remains to be known. The mechanisms that
      underlie the internalization of nER II (non-activated estrogen receptor,
      deglycosylated) have been identified to a certain extent. The question remains:
      is the primary location of the ERalpha also the plasma membrane? If that is the
      case, it will be a challenging task to identify the molecular events that
      underlie the plasma membrane-to-nucleus movement of ERalpha. The internalization
      mechanisms for the two 66kDa plasma membrane ERs, following hormone binding,
      appear to be distinct and without any overlaps. Interestingly, while the major
      gene regulatory role for ERalpha appears to be at the level of transcription, the
      nER II has its major functional role in post transcriptional mechanisms. The
      endoplasmic reticulum associated anchor protein-55 (ap55) that was recently
      reported from the author's laboratory needs a closer look. It is a high affinity
      estrogen binding protein that anchors the estrogen receptor activation factor (E
      RAF) in an estrogen-mediated event. It will be interesting to examine whether
      ap55 bears any structural similarity with either ERalpha or ERbeta.

PMID- 16423449
TI  - Identifying putative contraceptive targets by dissecting signal transduction
      networks in the epididymis using an in vivo electroporation (electrotransfer)
      approach.
AB  - Our studies have focused on understanding how the initial segment is regulated,
      in particular, by testicular luminal fluid factor(s). Our working hypothesis is
      that testicular luminal fluid growth factors, e.g. FGFs, regulate initial segment
      function via activation of signal transduction pathways and PEA3 family
      transcription factors. These, in turn, regulate downstream genes that are
      important for providing an appropriate fluid milieu for the protection and
      survival of sperm and the initial segment. To test this hypothesis and to look
      for potential contraceptive targets, we used an in vivo electroporation technique
      to introduce dominant-negative plasmids of FGF Receptor 1 and ERM into the
      initial segment of the rat epididymis. The levels of several putative downstream
      genes were estimated using quantitative-PCR (q-PCR). Data suggests that initial
      segment genes are regulated by 5alpha-reductase-dependent and -independent
      pathways and that multiple growth factor pathways are activated to coordinate the
      expression of these genes.

PMID- 16423451
TI  - Brachioradial pruritus--a peculiar neuropathic disorder.
AB  - The case is presented of a middle-aged woman who suffered from lancinating itch
      on the dorsolateral aspect of the upper arm after a loco-regional injury, first
      on the right and later on the left side. Brachioradial pruritus (BRP) was
      diagnosed. Neurophysiologic examination was compatible with a neuropathy at the
      C5-C6 level, while a negative nerve root block supported an additional central
      impact. The presumed pathophysiology of BRP is discussed in terms of a
      neuropathic disorder. We suggest that damage from whatever cause from either the
      cutaneous nerves or from the more proximal sensory pathways may be the causative
      physiopathologic basis for this enigmatic disorder. BRP was refractory to
      different therapeutic approaches, except to lamotrigine. As BRP presents a
      therapeutic challenge, it seems important to report lamotrigine as a potential
      new therapy.

PMID- 16423450
TI  - Eppin: an effective target for male contraception.
AB  - Eppin (epididymal protease inhibitor) is a member of the whey acidic protein
      (WAP)-type four-disulfide core (WFDC) gene family. This study provides updated
      information on Eppin and the Eppin-like genes within the Eppin cluster on human
      chromosome 20. A virtual structural model of the Eppin protein demonstrates that
      the C-terminal half of Eppin is structurally homologous to the Kunitz-type
      trypsin inhibitor. The Eppin N-terminal may have structural similarities to
      defensin-type molecules, rather than to that of the WAP consensus sequence. Human
      spermatozoa have a receptor for Eppin. When recombinant semenogelin (Sg) is
      digested with PSA many low molecular weight fragments are produced. However, when
      Eppin is bound to Sg, digestion by PSA is modulated. Addition of antibodies to
      the C-terminal of Eppin resulted in blocking PSA activity modulation. We can
      hypothesize from our analysis of anti-Eppin epitopes on Eppin that when anti
      Eppin antibodies are bound to Eppin on the sperm surface they block the binding
      site for semenogelin.

PMID- 16423452
TI  - Use of Fenton oxidation to improve the biodegradability of a pharmaceutical
      wastewater.
AB  - The applicability of Fenton's oxidation to improve the biodegradability of a
      pharmaceutical wastewater to be treated biologically was investigated. The
      wastewater was originated from a factory producing a variety of pharmaceutical
      chemicals. Treatability studies were conducted under laboratory conditions with
      all chemicals (having COD varying from 900 to 7000 mg/L) produced in the factory
      in order to determine the operational conditions to utilize in the full-scale
      treatment plant. Optimum pH was determined as 3.5 and 7.0 for the first
      (oxidation) and second stage (coagulation) of the Fenton process, respectively.
      For all chemicals, COD removal efficiency was highest when the molar ratio of
      H(2)O(2)/Fe(2+) was 150-250. At H(2)O(2)/Fe(2+) ratio of 155, 0.3M H(2)O(2) and
      0.002 M Fe(2+), provided 45-65% COD removal. The wastewater treatment plant that
      employs Fenton oxidation followed by aerobic degradation in sequencing batch
      reactors (SBR), built after these treatability studies provided an overall COD
      removal efficiency of 98%, and compliance with the discharge limits. The
      efficiency of the Fenton's oxidation was around 45-50% and the efficiency in the
      SBR system which has two reactors each having a volume of 8m(3) and operated with
      a total cycle time of 1 day, was around 98%, regarding the COD removal.

PMID- 16423453
TI  - Wind-induced dust generation and transport mechanics on a bare agricultural
      field.
AB  - Strong atmospheric winds may cause wind erosion and dust emissions on bare, dry,
      erodible fields. Since these dust emissions may exceed particulate matter limits
      established by the United States Environmental Protection Agency, information on
      dust generation and transport mechanics is needed to determine the particulate
      hazard of dust sources. Measurements of climatic variables and airborne sediment
      mass and concentration were made during three strong wind events on a bare, fine
      sandy loam field in west Texas. This study clearly shows that dust flux estimates
      were very sensitive to dust concentration measurement height. PM10 flux values
      estimated between heights of 2 and 5m were 2-5 times those estimated between
      heights of 5 and 10 m. Tower placement in relation to the upwind unerodible
      boundary produced significant differences in dust flux that varied with storm
      intensity. During the most intense storm event, the PM10 flux between heights of
      2 and 5m measured at the tower 200 m from the unerodible boundary was almost 2.5
      times as that measured at the tower 100 m from the unerodible boundary. Vertical
      PM10 dust flux was closely related with horizontal sediment flux only when the
      winds came from the same direction during the entire duration of horizontal
      sediment flux measurements.

PMID- 16423454
TI  - Estimating windblown PM-10 emissions from vacant urban land using GIS.
AB  - This paper presents a Geographic Information Systems (GIS)-based methodology to
      estimate annual area-wide airborne particulate matter with an aerodynamic
      diameter of less than 10 microm (PM-10) emissions, and identify zones with high
      emissions in order to efficiently implement mitigation strategies. Application of
      the methodology is demonstrated using the land disposal boundary within Clark
      County, NV as the study area, which is currently classified as a non-attainment
      area by United States Environmental Protection Agency (US EPA). The estimated PM
      10 emissions depend on the extent of disturbed vacant land area, undisturbed
      vacant land area, emission factors by soil group, and wind speeds. Portable wind
      tunnel field test data were used to estimate emission factors at 78 sites in the
      study area. Portable wind tunnel results were categorized by the wind speed range
      and the corresponding site soil group in order to estimate emission factors by
      soil group and the wind speed range. Wind speed data were obtained from the Clark
      County Health District's air quality monitoring stations. The proximal area over
      which the wind speeds are same is obtained by constructing "Thiessen" polygons
      around each wind speed monitoring station. PM-10 emissions were estimated as a
      function of the extent of disturbed vacant lands, the measured or estimated
      erodibility of the soil surfaces, and the intensity, duration and frequency of
      erosive wind events.

PMID- 16423455
TI  - Role of heteroatoms in activated carbon for removal of hexavalent chromium from
      wastewaters.
AB  - Heteroatoms are elements including sulfur, nitrogen, oxygen and hydrogen which
      are found on the surface of activated carbons. This study investigated the
      surface modification arising from heteroatoms bonding to carbon aromatic rings
      within the activated carbon and their corresponding influence on the chromium
      adsorption process. Activated carbons were prepared from bagasse by physical.
      Chromium removal capacities of these activated carbons by adsorption and
      reduction were determined. Models which related the chromium adsorption and
      reduction capacities of activated carbons to carbon acidity and heteroatom site
      concentrations were established using multi-variable linear regression method. It
      was found the individual heteroatoms contributed separately to the basicity of
      the carbon which in turn determined the mechanism by which chromium was removed
      from solution. The surface areas of the carbons were also observed to influence
      the adsorption and reduction of chromium. These understandings provide the
      fundamental method of optimising chromium removal through suitable control of
      carbon surface chemistry and textural properties.

PMID- 16423456
TI  - Decoloration of textile wastewater by means of a fluidized-bed loop reactor and
      immobilized anaerobic bacteria.
AB  - Textile wastewater was treated by means of a fluidized-bed loop reactor and
      immobilized anaerobic bacteria. The main target of this treatment was
      decoloration of the wastewater and transformation of the non-biodegradable azo
      reactive dyes to the degradable, under aerobic biological conditions, aromatic
      amines. Special porous beads (Siran) were utilized as the microbial carriers.
      Acetic acid solution, enriched with nutrients and trace elements, served both as
      a pH-regulator and as an external substrate for the growth of methanogenic
      bacteria. The above technique was firstly applied on synthetic wastewater (an
      aqueous solution of a mixture of different azo-reactive dyes). Hydraulic
      residence time was gradually decreased from 24 to 6 h over a period of 3 months.
      Full decoloration of the wastewater could be achieved even at such a low
      hydraulic residence time (6 h), while methane-rich biogas was also produced. The
      same technique was then applied on real textile wastewater with excellent results
      (full decoloration at a hydraulic residence time of 6 h). Furthermore, the
      effluent proved to be highly biodegradable by aerobic microbes (activated
      sludge). Thus, the above-described anaerobic/aerobic biological technique seems
      to be a very attractive method for treating textile wastewater since it is cost
      effective and environment-friendly.

PMID- 16423457
TI  - Estradiol prevents the focal cerebral ischemic injury-induced decrease of
      forkhead transcription factors phosphorylation.
AB  - Estradiol prevents neuronal cell death through the inhibition of apoptotic
      signals. This study investigated whether estradiol modulates the anti-apoptotic
      signal through the activation of Akt and its downstream targets, including
      forkhead transcription factors FKHR and FHKRL1. Adult female rats were
      ovariectomied and treated with estradiol prior to middle cerebral artery
      occlusion (MCAO). Brains were collected 24 h after MCAO and infarct volumes were
      analyzed. Estradiol administration significantly reduced infarct volume and
      decreased the positive cells of TUNEL staining in the cerebral cortex. Potential
      activation was measured by phosphorylation of Akt at Ser473, pFKHR at Ser256, and
      pFKHRL1 at Thr32 using Western blot analysis and immunohistochemistry. Estradiol
      prevents the injury-induced decrease of pAkt, pFKHR, and pFKHRL1. Further, in the
      presence of estradiol, the interaction of pFKHRL1 and 14-3-3 increased, compared
      to that of oil-treated animals. Our findings suggest that estradiol plays a
      potent protective role against brain injury and that Akt activation and FKHR
      phosphorylation by estradiol mediated these protective effects.

PMID- 16423458
TI  - Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic
      or local administration?
AB  - Recent studies showed the therapeutic effect of bone marrow stromal cells (BMSC)
      after spinal cord injury (SCI). In the present study, we compared the effect of
      systemic and local administration of BMSC in adult Wistar rats suffering chronic
      paraplegia as consequence of severe SCI. Adult Wistar rats were subjected to a
      weight-drop impact causing complete paraplegia, and 3 months later, all the
      animals remained without signs of functional recovery. At this moment, 3 x 10(6)
      BMSC were injected intravenously (n: 20) or into traumatic spinal cord cavity (n:
      20). Outcome was evaluated until sacrifice of the animals, 6 months later, using
      the Basso-Beattie-Bresnehan (BBB) score, the cold spray test, and measuring the
      thigh perimeter. After sacrifice, samples of spinal cord tissue were studied
      histologically. The results showed that intravenous administration of BMSC
      achieves some degree of functional recovery when compared to controls.
      Nevertheless, administration of BMSC into postraumatic spinal cord cavity
      promotes a clear and progressive functional recovery, significantly superior to
      the recovery obtained by means of the intravenous administration. This effect is
      associated to long-term presence of BMSC in the injured spinal cord tissue, with
      images suggesting neuronal differentiation and spinal cord reconstruction.

PMID- 16423459
TI  - Nerve growth factor increases survival of dopaminergic graft, rescue nigral
      dopaminergic neurons and restores functional deficits in rat model of Parkinson's
      disease.
AB  - In the present study, an attempt has been made to explore the neuroprotective and
      neurorescue effects of nerve growth factor (NGF) on grafted cells and on host
      nigral dopaminergic neurons, respectively. NGF was co-transplanted with fetal
      ventral mesencephalic cells (VMC) in the striatum of 6-hydroxydopamine (6-OHDA)
      lesioned rat model of Parkinson's disease (PD). In the other groups fetal VMC and
      NGF were transplanted alone. Twelve weeks post-transplantation, a significant
      restoration was observed in D-amphetamine induced rotations (stereotypy),
      spontaneous locomotor activity, striatal and nigral dopamine (DA) and 3,4
      dihydroxy-phenyl acetic acid (DOPAC) levels in co-transplanted rats as compared
      to VMC alone transplanted rats. Higher number of surviving tyrosine hydroxylase
      immunoreactive (TH-ir) neurons and significantly increased fiber outgrowth from
      graft was evident in co-transplanted rats as compared to VMC alone transplanted
      rats. Further, a significant increase was also observed in substantia nigra TH-ir
      neurons count in co-transplanted rats, exhibiting a potential neuroprotective and
      neurorescue effects of NGF on nigrostriatal dopaminergic neurons. The results
      suggest that NGF at the time of transplantation exhibits neuroprotective effect
      on transplanted VMC as well as neurorescue effect on remaining host nigral
      dopaminergic neurons, leading to better functional restoration.

PMID- 16423460
TI  - Nociceptin/orphanin FQ evokes knee joint pain in rats via a mast cell independent
      mechanism.
AB  - Nociceptin/orphanin FQ (N/OFQ) is an opioid-like neuropeptide that has been shown
      to cause peripheral sensitization of knee joint afferents; however, the effect of
      the peptide on joint pain behaviour is unknown. In addition to having a direct
      effect on peripheral nerves, N/OFQ has also been shown to activate connective
      tissue mast cells causing the local release of potentially pain causing
      mediators. The present study tested the effect of peripherally administered N/OFQ
      on joint pain and examined whether synovial mast cells contribute to these
      responses. Hindlimb weight bearing and von Frey hair algesiometry were measured
      before and following a single injection of N/OFQ in the vicinity of the right
      knee of male Wistar rats. Compared to saline-treated controls, N/OFQ caused a
      conspicuous shift in hindlimb weight bearing in favour of the contralateral non
      injected leg. Similarly, paw withdrawal threshold and latency were significantly
      reduced following N/OFQ administration indicative of secondary hyperalgesia. To
      test the involvement of synovial mast cells in these pain reactions, a separate
      group of rats were treated with the mast cell stabilizer cromolyn (20 mg/kg s.c.)
      5 min prior to N/OFQ injection. Cromolyn treatment had no significant effect on
      N/OFQ-induced weight bearing deficit nor secondary hyperalgesic responses. In
      conclusion, these data support the premise that N/OFQ has a pain causing effect
      in the periphery which occurs independently of mast cell activation.

PMID- 16423461
TI  - Right hemisphere dominance in perceiving coherence of visual events.
AB  - The visual world consists of static pictures as well as of coherent visual
      events. The present study investigated neural substrates underlying the
      perception of coherence of visual events that evolves over time. We measured
      brain activity using functional magnetic resonance imaging (fMRI) while adults
      watched briefly presented static images that were extracted from movie clips
      depicting coherent visual events. The images were presented either in the
      coherent order as they were displayed in the movie clips or in a random order.
      Relative to the random order presentation condition, static images presented in
      the coherent order generated stronger activation in the right middle temporal
      cortex, the right posterior superior temporal cortex, and the right inferior
      postcentral gyrus. The results provide neuroimaging evidence for the dominance of
      the right hemisphere in perceiving coherent visual events.

PMID- 16423462
TI  - Striatal microinjections of nitric oxide synthase inhibitors and L-arginine fail
      to exert effects on paroxysmal dystonia in the dtsz mutant.
AB  - Primary dystonia is a common movement disorder with an unknown pathophysiology,
      but basal ganglia dysfunctions seem to play a critical role. Previous studies in
      the dtsz mutant hamster, an animal model of primary paroxysmal dystonia,
      demonstrated a deficit of striatal gamma-amino-butyric acid (GABA) containing
      interneurons, which normalized at the age of the spontaneous remission of the
      symptoms. Whereas the reduction of striatal parvalbumin-reactive interneurons is
      thought to be critically involved in the pathogenesis of dystonia in the hamster
      mutant, the impact of a reduced density of nitric oxide synthase (NOS) reactive
      interneurons within the striatum is still unclear. Beside GABA, these
      interneurons contain somatostatin, neuropeptide Y, nicotinamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d) and neuronal NOS, an enzyme which
      produces NO after the activation of the interneurons. In order to clarify if the
      reduced density of NOS-reactive interneurons contributes by an altered striatal
      production of nitric oxide (NO) to the occurrence of dystonic attacks in the
      hamster mutant, we performed microinjections of the NOS inhibitors 7
      nitroindazole (7-NI) and Nomega-propyl-L-arginine (NPLA) and of the precursor of
      NO, L-arginine, into the striata of dtsz hamsters. Neither 7-NI (0.1 and 0.4
      microg per hemisphere) and NPLA (2.5, 5 and 7.5 microg per hemisphere) nor L
      arginine (9 and 18 microg per hemisphere) exerted any effects on the severity of
      dystonic movements in the dtsz mutant. Therefore, a critical involvement of
      striatal changes of NO in the pathophysiology of dystonic attacks in the dtsz
      hamster cannot be confirmed by the results of these pharmacological examinations.
      In view of the ontogenetic reduction of the other types of GABAergic
      interneurons, the deficit of NOS-reactive interneurons is possibly due to the
      same underlying unknown mechanism, but is less important for the pathophysiology
      of primary paroxysmal dystonia in the dtsz hamster mutant.

PMID- 16423463
TI  - Genetic study of Sardinian patients with Alzheimer's disease.
AB  - We describe the genetic analysis of an Alzheimer's disease (AD) sample derived
      from a genetically isolated population. Genetic assessment included the analysis
      of genes involved in AD, such as the genes for amyloid precursor protein (APP),
      presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some
      proteins that constitute the gamma-secretase complex: nicastrin (NCSTN),
      presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E
      (APOE). Using polymerase chain reaction and single strand conformational
      polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation
      in PSEN1. Furthermore, we found an intronic +17G>C polymorphism in PEN2 which, in
      homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared
      to controls, and one haplotype in the NCSTN gene which was linked to EOAD and
      familial AD (FAD). Finally, the genotyping of APOE confirmed that the varepsilon4
      allele could be a risk factor for the onset of AD, in particular for FAD
      subjects. In conclusion, these results show the existence of Sardinian genetic
      peculiarities, essential in studies regarding genetically inherited and
      multifactorial disorders, as AD.

PMID- 16423464
TI  - Electro-olfactograms are present when odorous stimuli have not been perceived.
AB  - After chemical stimulation of the human olfactory epithelium it is possible to
      record a negative response (electro-olfactogram, EOG) which is interpreted as the
      summated generator potential of olfactory neurons. The aim of the present
      investigation was to test whether the EOG is present when olfactory stimuli have
      not been perceived. Stimulation was performed with vanillin and eugenol at
      supraliminal and subliminal levels. Twelve healthy volunteers participated in the
      experiments. Stimuli were applied at an interstimulus interval of approximately
      60s. Although recordings were successful in 4 of the 12 subjects, for both
      stimulants EOG could be obtained even when the stimuli had not been perceived by
      the subjects. EOG recordings in response to supra- and subliminal stimuli
      exhibited no major differences, except for the onset of the EOG in response to
      subliminal eugenol-stimuli which were prolonged compared to supraliminal
      stimulation. All in all, the present data provide a physiological basis for the
      subliminal influence of odorous stimuli on human behavior.

PMID- 16423466
TI  - Quantitative Fresnel Lorentz microscopy and the transport of intensity equation.
AB  - Imaging of the magnetic structure of thin films by the Fresnel mode of Lorentz
      microscopy has been re-evaluated in terms of the Amperian current density within
      a sample. The conditions for which this imaging can be treated as linear are
      discussed for quantitative application. Additionally, the consequences for
      magnetic phase reconstruction using the transport of intensity equation for
      defocused images are considered. While the range of applicability may initially
      appear rather limited examples of objects containing different spatial frequency
      components are used to illustrate the possibilities where relatively large
      defocus values may be used.

PMID- 16423465
TI  - Gaze tracking accuracy in humans: two eyes are better than one.
AB  - Many people viewing a small distant object report the use of a dominant eye,
      which may change when viewing the same object in right or left viewing fields.
      This study was designed to determine if the accuracy in left and right gaze
      recordings from a video-based binocular eye tracking system with eye-head
      integration would change when observers looked at targets in different viewing
      fields. We also wanted to determine whether system accuracy was best using the
      dominant eye, the average of both eyes or an alignment switching strategy for
      various viewing fields. Bilateral eye and head movements were recorded to
      determine point of gaze (POG) for subjects viewing targets with the head neutral
      or rotated left or right with a stationary body (static) or while stepping toward
      a target and back (dynamic). Constant, absolute and variable POG and rotational
      errors were determined. Results showed that although errors were highest in the
      static condition for POG errors and in the dynamic condition for rotational
      errors, absolute rotational angle errors were similar for static and dynamic
      conditions, indicating that subject to object distance played an important role
      in determining POG errors. Furthermore, errors were not consistently lower for a
      given eye or for a given eye within a specific viewing field for the head
      rotations performed. Since low errors across the viewing fields were found by
      averaging left and right errors, it was concluded that this average and should be
      used in future studies involving relatively small eye-in-head rotations.

PMID- 16423468
TI  - Oxidative stress may underlie the sex differences seen in steroid-induced
      osteonecrosis models.

PMID- 16423469
TI  - Medicine and the space odyssey.
AB  - Up to the mid-1960s, science and technology (including medicine) were generally
      regarded as exciting, beautiful and spiritually enthralling; and the space
      odyssey seemed a symbol of the optimistic future of humankind. The early
      seventies saw a growing disillusionment with space travel as part of a mood of
      cultural pessimism and anti-modernization - and this combined with a resurgence
      of therapeutic nihilism in medicine. But recent discussions of renewed space
      exploration and a Mars mission may be evidence of a changing zeitgeist, with
      Western culture moving towards a bolder and more optimistic attitude. The
      adventure of space travel, exploration and colonization could be seen as both a
      barometer of cultural optimism, and an enterprise which would feed-back into
      cultural optimism for many decades to come. Medical science could also be a
      beneficiary; since greater boldness and optimism would be likely to renew the
      goals of medicine to do positive good - as contrasted with the necessary, but
      relatively uninspiring, requirement to minimize risk and harm. In a modernizing
      society humankind needs to look outward as well as inward: we need a frontier,
      and we need to grow. A resurgent space odyssey may be the best way that this can
      be enacted.

PMID- 16423467
TI  - Serological evidence of Neospora caninum in dual-purpose cattle herds in
      Venezuela.
AB  - Bovine neosporosis is a parasitic disease produced by Neospora caninum that
      induces abortion in cows, and consequently has a negative impact on the herd's
      reproductive efficiency. The main objective of this research was to determine the
      serological evidence of N. caninum in cattle herds from Venezuela using an
      indirect antibody capture ELISA test. Four hundred and fifty-nine (459) serum
      samples from crossbred adult cows were collected to be tested for Neospora
      antibodies. The sampled cows came from 15 large farms located in eight important
      cattle states that have predominant dual-purpose production systems (cattle from
      these farms are used for both milk and meat production). Fifty-two cows (11.3%)
      were seropositive to N. Caninum. Thirteen (86.7%) of 15 studied herds had cows
      seropositive to N. caninum. The average within-herd seroprevalence was 11.5%
      (range 3.8-36.7%). Cows that aborted in some of these farms had 2.71 (P: 0.009)
      greater odds to be seropositive when compared to cows that did not abort. Each
      one of the eight states represented in our study had seropositive animals. These
      results are the first evidence of exposure to N. caninum in Venezuelan cattle
      herds, indicating the possible circulation of this pathogen in the country.
      Further epidemiological studies should be granted to determine the spread of the
      disease in the Venezuelan cattle industry and its associated risk factors.

PMID- 16423470
TI  - Characterization of the NASP promoter in 3T3 fibroblasts and mouse spermatogenic
      cells.
AB  - NASP (nuclear autoantigenic sperm protein) is a histone H1 binding protein
      expressed in all cells undergoing division. We have previously reported the
      sequence for the mouse NASP gene and analyzed its proximal promoter region in
      silico to determine putative regulatory regions. In this report we describe
      various factors regulating the transcription of NASP. Luciferase assays using 3T3
      fibroblasts show that the region +9 to -135 nt (PR1C) provides the core
      transcriptional activity for NASP and that extending this region out to -976
      nucleotides partially represses activity. However, when luciferase reporter
      assays were done in transfected pachytene spermatocytes, the cells that exhibit
      the highest NASP expression, a different gene regulation picture was revealed. In
      spermatogenic cells, PR1C is still a relatively strong core promoter, but unlike
      3T3 cells, if the construct is extended to -3002 nucleotides there is marked
      enhancement of transcription. Electrophoretic mobility shift assays with 3T3
      nuclear extracts were used to study the PR1C core promoter in greater detail. In
      the region immediately upstream of the transcription initiation site we
      identified two closely associated Sp1 binding sites and a binding site for an Ets
      family member. Supershift assays further confirmed the presence of Sp1 bound to
      their respective sites suggesting that Sp1 and Ets are the primary activators of
      the NASP promoter.

PMID- 16423471
TI  - Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell
      motility and invasion.
AB  - Cellular migration and invasion are critical for important biological processes
      including cancer metastasis. We previously reported that uteroglobin (UG), a
      multifunctional secreted protein, binds to several cell types inhibiting
      migration and invasion [G.C. Kundu, A.K. Z. Zhang Mandal, G. Mantile-Selvaggi,
      A.B. Mukherjee (1998) Uteroglobin (UG) suppresses extracellular matrix invasion
      by normal and cancer cells that express the high affinity UG-binding proteins. J
      Biol Chem. 273: 22819-22824]. More recently, we reported that HTB-81
      adenocarcinoma cells, which do not bind UG, are refractory to UG-mediated
      inhibition of migration and invasion [Z. Zhang, G.C. Kundu, D. Panda, A.K. Mandal
      et al. (1999) Loss of transformed phenotype in cancer cells by overexpression of
      the uteroglobin gene. Proc Natl Acad Sci U S A. 96, 3963-3968]. Since UG shares
      several biological properties with lipocalin-1 that mediates some of its
      biological effects via its receptor (Lip-1R), we sought to determine whether UG
      might interact with Lip-1R and inhibit migration and invasion of HTB-81 cells. To
      address this question, we first transfected COS-1 cells, which do not bind UG,
      with a Lip-1R-cDNA construct and performed binding assays using 125I-human UG
      (hUG). The results show that hUG binds Lip-1R on these cells with high
      specificity. Further, transfection of HTB-81 cells with the same construct
      yielded 125I-hUG binding with high affinity (Kd=18 nM) and specificity. The hUG
      Lip-1R interaction was further confirmed by transfecting HTB-81, HTB-30 and HTB
      174 cells, which are refractory to UG-binding, with a green fluorescent protein
      (GFP)-Lip-1R-cDNA construct and testing for Lip-1R-hUG colocalization by
      fluorescence microscopy. Finally, we demonstrate that Lip-1R-hUG interaction on
      Lip-1R transfected HTB-81 cells renders them fully responsive to hUG-mediated
      inhibition of migration and invasion. Taken together, these results suggest that
      Lip-1R is at least one of the UG-binding proteins through which UG exerts anti
      motility and anti-invasive effects.

PMID- 16423472
TI  - Repertoire of mouse ectodysplasin-A (EDA-A) isoforms.
AB  - Mutations in ectodysplasin-A (EDA) cause loss of hair, sweat glands, and teeth in
      man and mouse. Isoform EDA-A1 protein shows partial rescue of the affected Tabby
      mouse phenotypes, suggesting that other isoforms may be required for full
      function. We describe genomic structure for five EDA isoforms, EDA-A1', A5, A5',
      A6, and A6', in addition to the previously known EDA-A1, A2, A3, and A4. The
      novel isoforms together account for approximately 12% of total EDA transcripts.
      The most different, EDA-A6 and A6', which lack the critical domain for
      interaction with NF-kappaB-activating receptors, were nevertheless confirmed to
      be present in mouse and human skin tissue. Other isoforms, EDA-A5 and A5', for
      example, activated NF-kappaB through receptors EDAR and XEDAR. These properties
      make new isoforms candidates for modulators of EDA function.

PMID- 16423473
TI  - Klebsiella to Salmonella gene transfer within rumen protozoa: implications for
      antibiotic resistance and rumen defaunation.
AB  - The rumen has long been thought to be a site of gene transfer for microorganisms.
      Rumen protozoa (RPz) are active predators of bacteria that can harbor antibiotic
      resistance genes. In this study, RPz were assessed as sites of gene transfer
      between two bacterial species, Salmonella and Klebsiella. One Klebsiella isolate
      carried a plasmid bearing bla(CMY-2), encoding an extended-spectrum beta
      lactamase conferring ceftriaxone resistance, while the Salmonella was susceptible
      to ceftriaxone yet capable of thriving within protozoa. In vitro studies revealed
      that ceftriaxone-resistant Salmonella could be isolated following co-incubation
      of Salmonella and Klebsiella with RPz obtained from adult cattle and goats.
      Ceftriaxone-resistant Salmonella were not recovered in the presence of an
      inhibitor of protozoa engulfment or when a protozoa-sensitive Salmonella was part
      of the co-incubation. This transfer event was additionally observed in vitro for
      protozoa-independent stressors although at a significantly lower frequency. The
      gene transfer event was related to bacterial conjugation since a conjugation
      inhibitor, nalidixic acid, perturbed the phenomenon. Ceftriaxone-resistant
      Salmonella were recovered from calves, sheep, and goats co-challenged with
      ceftriaxone-resistant Klebsiella and ceftriaxone-sensitive Salmonella. However,
      the transfer event was not observed in calves and sheep that were defaunated
      prior to the co-challenge. Moreover, Salmonella transconjugants were isolated
      from separate bovine in vivo studies involving a Klebsiella donor carrying a
      plasmid conferring colicin activity while no such transconjugants were obtained
      from defaunated calves. These results provide an important basis for evaluating
      and preventing the spread of antibiotic resistance and other selective advantages
      for pathogens present in ruminants.

PMID- 16423474
TI  - Association between race and hot flashes in midlife women.
AB  - OBJECTIVE: Studies suggest that African American women may have a greater risk of
      hot flashes compared to Caucasian women, but the reasons for this are unknown.
      This study tested the hypothesis that African American women have an increased
      risk of hot flashes due to racial differences in risk factors for hot flashes,
      including high body mass index (BMI) and lower estrogen levels. METHODS: A
      population-based study was conducted among women aged 45-54 years. Participants
      were divided into women who reported ever experiencing hot flashes (n=356) and
      women who reported never experiencing hot flashes (n=257). Participants provided
      a blood sample for hormone assays, were weighed and measured, and completed a
      questionnaire. RESULTS: Among peri-menopausal women, African American women were
      more likely than Caucasian women to report any hot flashes (RR=2.08), severe hot
      flashes (RR=2.19), and hot flashes for more than 5 years (RR=1.61). The risk
      ratios for the associations between race and the hot flash outcomes were
      attenuated after controlling for other important hot flash risk factors (i.e.
      obesity and low estrogen levels). CONCLUSIONS: African American women have an
      increased risk of hot flashes compared to Caucasian women due to racial
      differences in a number of risk factors for hot flashes, including advanced age,
      obesity, current smoking, less than 12 drinks in the past year, and lower
      estrogen levels.

PMID- 16423475
TI  - Effects of incorporated drugs on degradation of novel 2,2'-bis(2-oxazoline)
      linked poly(lactic acid) films.
AB  - Earlier studies have indicated that the degradation rate of poly(lactic acid)
      (PDLLA) can be modified by using 2,2'-bis(2-oxazoline) as a chain extender in
      polymer synthesis to form a lactic acid-based poly(ester-amide) (PEA). In the
      present study, the effect of an incorporated drug on the degradation rate of the
      PEA was evaluated. The model drugs, neutral guaifenesin, acidic sodium salicylate
      (pK(a) 3.0) and basic timolol (pK(a) 9.2), were incorporated into solvent cast
      PDLLA and PEA films. The drug content in the films was 2% (w/w). The degradation
      studies were carried out in PBS (pH 7.4, 37 degrees C); the resulting decrease in
      molecular weight of polymers was determined by size exclusion chromatography and
      the weight loss of films was measured. In addition, the drug release from the
      films in PBS (pH 7.4, 37 degrees C) was studied. The model drugs were released
      from the PDLLA and PEA films in a biphasic or triphasic manner. The final fast
      release phase of the drugs from both PDLLA and PEA films started when the
      molecular weight (M(n)) of the polymer had decreased close to 15,000 g/mol. The
      degradation rate of the PDLLA films was clearly enhanced by incorporated sodium
      salicylate or timolol. Whereas, the degradation rate of the PEA film was not
      enhanced by the incorporated drugs. The present results indicate that when
      compared to the PDLLA film, degradation rate of the PEA film in the presence of
      the drug is more predictable.

PMID- 16423476
TI  - Preparation of ethyl cellulose/methyl cellulose blends by supercritical
      antisolvent precipitation.
AB  - The supercritical antisolvent (SAS) technique was used to prepare ethyl
      cellulose/methyl cellulose blends, two biocompatible polymers commonly used as
      drug carriers in controlled delivery systems. Ethyl cellulose is widely used as a
      drug carrier. The drug release of the delivery devices can be controlled to some
      extent by addition of a water-soluble or water swellable polymer, such as methyl
      cellulose. This leads to the solubility enhancement of poorly water-soluble
      molecules. SAS experiments were carried out at different operational conditions
      and microspheres with mean diameters ranging from 5 to 30 microm were obtained.
      The effect of CO(2) and liquid flow, temperature and pressure on particle size
      and particle size distribution was evaluated. The microspheres were precipitated
      from a mixture of dichloromethane (DCM) and dimethylsulfoxide (DMSO) (4:1 ratio).
      The best process conditions for this mixture were according to our study 40
      degrees C and 80 bar.

PMID- 16423477
TI  - G-CSF loaded biodegradable PLGA nanoparticles prepared by a single oil-in-water
      emulsion method.
AB  - A new formulation method was developed for preparing poly(D,L-lactic-co-glycolic
      acid) (PLGA) nanoparticles loaded with recombinant human granulocyte colony
      stimulating factor (rhG-CSF). Lyophilized rhG-CSF powder and PLGA polymer were
      directly co-dissolved in a single organic phase, and the resulting solution was
      dispersed into an aqueous solution. PLGA nanoparticles encapsulating rhG-CSF were
      produced by a spontaneous emulsion/solvent diffusion method. In this manner, rhG
      CSF was molecularly dissolved in the polymer phase. Release profile of rhG-CSF
      from PLGA nanoparticles was compared with those from two kinds of PLGA
      microparticles which were separately prepared by either single oil-in-water (O/W)
      or double water-in-oil-in-water (W/O/W) emulsion technique. The sizes of rhG-CSF
      loaded nanoparticles, O/W microparticles, and W/O/W microparticles were about 257
      nm, 4.7 microm, and 4.3 microm, respectively. For rhG-CSF nanoparticles, about
      90% of encapsulated rhG-CSF was released out in a sustained manner from PLGA
      nanoparticles over a 1 week period, but for rhG-CSF microparticles, only about
      20% of rhG-CSF could be released out during the same period. Reversed phase and
      size exclusion chromatograms revealed that the structural integrity of released
      rhG-CSF from nanoparticles was nearly intact, compared to that of native rhG-CSF.

PMID- 16423478
TI  - Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic
      mice with induced human cancer tumors.
AB  - Radiolabeled peptides, like the somatostatin analogs, have been used for peptide
      receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine
      tumors. The eight amino acid peptide 3-(2-naphthalenyl)-D-alanyl-L-cysteinyl-L
      tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide,cyclic(2-->7)
      disulfide (9Cl) (lanreotide) was found to bind to the five somatostatin tumor
      receptors. Lanreotide has been labeled via the bifunctional chelating agent,
      DOTA, to (111)In, and (90)Y. A direct labeling method was used to label
      lanreotide with (188)Re. Athymic mice with implanted human cancer tumors (uterine
      cervix, renal, and neuroblastoma) were injected with radiochemically pure (188)Re
      lanreotide (1.11 MBq). The percent injected activity (%IA/g) from serial blood
      samples was the input data for the WinNonlin computer program to obtain
      radiopharmacokinetic parameters. The organs' percent injected activity per gram
      of tissue (%IA/g) was extrapolated to the weights of a 70 kg male model organs
      and the number of nuclear transitions (N) were the input for the OLINDA/EXM
      program to obtain dosimetry estimates. Induced uterine-cervix tumors (HeLa cells)
      show a mean 2.4 %IA/g uptake up to 24 h and the tumor/blood ratio was over 1.85
      (1.5-24 h post-injection) confirming (188)Re-lanreotide remains bound to the
      tumor. The estimated tumor absorbed dose was 460 mGy/MBq. Human effective dose
      was 0.0182 mSv/MBq. Therefore, (188)Re-lanreotide is a good candidate for PRMRT
      and a clinical trial is being planned in order to acquire individual dosimetric
      data.

PMID- 16423479
TI  - Analgesic and anticonvulsant effects of extracts from the leaves of Kalanchoe
      crenata (Andrews) Haworth (Crassulaceae).
AB  - Kalanchoe crenata Andr. (Crassulaceae) is a fleshy herbaceous plant used in the
      African traditional medicine as remedies against otitis, headache, inflammations,
      convulsions and general debility. In the present work, the analgesic effects of
      methylene chloride/methanol (1:1) (CH(2)Cl(2)/CH(3)OH) extract and its hexane,
      methylene chloride (CH(2)Cl(2)), ethyl acetate, n-butanol fractions and aqueous
      residue have been evaluated using acetic acid, formalin and pressure test. The
      anticonvulsant effects of the CH(2)Cl(2)/CH(3)OH extract were also investigated
      on seizures induced by pentylenetetrazol (PTZ 70 mg/kg), strychnine sulphate (STN
      2.5 mg/kg) and thiosemicarbazide (TSC 50 mg/kg). CH(2)Cl(2)/CH(3)OH extract and
      its fractions, administered orally at the doses of 150 and 300 mg/kg, exhibited
      protective effect of at least 30% on the pain induced by acetic acid. The
      CH(2)Cl(2) fraction at 300 mg/kg showed a maximal effect of 78.49%. The
      CH(2)Cl(2)/CH(3)OH extract and its CH(2)Cl(2) fraction at the doses of 150 and
      300 mg/kg significantly reduced the first phase of pain induced by formalin while
      the second phase was completely inhibited. The CH(2)Cl(2) fraction produced more
      than 45% reduction in the sensitivity to pain induced by pressure. The
      CH(2)Cl(2)/CH(3)OH extract of Kalanchoe crenata significantly increased the
      latency period in seizures induced by PTZ and significantly reduced the duration
      of seizures induced by the three convulsant agents. The extract protected 20% of
      animals against death in seizures induced by TSC and STN. These results suggest a
      peripheral and central analgesic activities as well as an anticonvulsant effect
      of the leaves of Kalanchoe crenata.

PMID- 16423480
TI  - Ethnopharmacological evaluation of the informant consensus model on anti
      tuberculosis claims among the Manus.
AB  - Ethnobotanists often utilize predictive models to analyze the potential of
      indigenously used medicinal plants. The most common of these prognostic models is
      the informant consensus model. This study evaluates use of this model through the
      analytical ethnopharmacology of Manus Province, Papua New Guinea (PNG). The
      informant consensus model enables researchers to prioritize plants for
      pharmacognostic evaluation, based on the relative frequency of plants cited in
      anthropological interviews. Fieldwork on Manus Island, PNG, led to the
      identification of 43 species of plants used in traditional medicine for
      persistent respiratory symptoms. Plants were collected, dried, micro-extracted
      using a new technique generated in our laboratory, and evaluated in vitro against
      Mycobacterium tuberculosis. The results, in the form of IC(50) values and
      modified selectivity indices (SI), were compared to the results of the
      anthropological models of informant consensus, and statistically compared through
      linear regression and t-tests. Results were not statistically significant
      (alpha=0.1), leading to the conclusions that the informant consensus assumptions
      were inaccurate in predicting anti-mycobacterial activity among the Manus for
      anti-TB claims.

PMID- 16423481
TI  - New multiplexes for Europe-amendments and clarification of strategic development.
AB  - Recently, the ENFSI/EDNAP groups issued advice on the design of the next
      generation of STR multiplexes in order to encourage standardisation within
      Europe. As the result of collaborative experimentation within the EDNAP group, we
      demonstrated that the low molecular weight STRs had substantial benefits to
      detect degraded samples. We subsequently recommended adoption of three new mini
      STR loci to improve the success rate of degraded DNA markers, concurrent with the
      reduction in size of the existing STR markers in current use. This also improves
      the discriminating power of the system which is important to improve the power of
      national DNA databases. Subsequent discussions have occurred with manufacturers
      and members of the ENFSI/EDNAP groups. Because significant time and investment is
      required to develop new multiplexes of 13+ STR loci, manufacturers indicated that
      it would be preferable to adopt a staged approach. Two differing, but parallel
      strategies have now emerged. The first strategy employs a 13 STR loci multiplex
      incorporating three mini-STRs into the current multiplex test. The second
      strategy employs a multiplex of six high molecular weight STRs (in current use),
      modified to provide smaller amplicons combined with an additional two loci of
      high discriminating power. Eventually, the two strategies will converge to
      provide a single multiplex of 15 STR loci. The process will be guided by the
      ENFSI/EDNAP groups.

PMID- 16423482
TI  - Stability of Delta(9)-tetrahydrocannabinol (THC) in oral fluid using the
      Quantisal collection device.
AB  - This article details the stability of Delta(9)-tetrahydrocannabinol (THC) in oral
      fluid during collection, extraction and storage. Oral fluid is being increasingly
      used as the specimen of choice for the detection of drug use in various
      applications. Studies to determine the extraction efficiency of THC from the
      collection buffer and stability under various laboratory storage conditions were
      carried out. THC was extracted from the collection pad and buffer with an average
      efficiency over 80% and was stable in Quantisal oral fluid extraction buffer when
      stored at refrigerated temperatures. Fluorescent lighting caused THC losses of
      over 50%, however the presence of the pad reduced the loss. In the dark, the loss
      of THC at room temperature was approximately 20% over 14 days. When stored with
      the serum separators in place, THC losses were significant. After 3 days, THC
      concentration was reduced by almost 30%, and after 14 days, 60% of the drug was
      lost and the losses were not concentration dependent.

PMID- 16423484
TI  - Beyond the myth: the mermaid syndrome from Homerus to Andersen. A tribute to Hans
      Christian Andersen's bicentennial of birth.
AB  - Mermaid or sirens have been part of the cultural tradition of the sailors during
      the first expeditions in the western world. The Siren's Myth appeared for a first
      time with Homer, who described in the Odyssey some singing creatures that lured
      the enchanted sailors to death. More frequently described with a bird body and a
      female head, sometimes the female part was extended to torso, with arms prolonged
      in sturdy claws. In the Latin literature Publius Ovidius Naso presented in the
      Metamorphoses these creatures. Proposed ethymology for the word "siren" seems to
      confirm the prerogatives of these creatures, related to magnetism, seduction,
      charm. The first figuration of Sirens resembling to fish-women was in the second
      century bc. Hans Christian Andersen provided to leave us the strongest legend of
      Siren in the well-known fairy tale "The Little Mermaid". Following this story,
      Sirens are definitely considered as beautiful half-fish women who lived in the
      bottom of the sea, having a lovely voice to be used when they rise up to allow
      sweeter the agony of the wrecked sailors. Beyond the Myth, may the Siren really
      exist? It can be hypothesized that these creatures probably were individuals
      affected by sirenomelia. In our literature and medical review, we describe the
      etiology of the disease, and we illustrated the anatomical features of fetuses
      affected by this pathology using MDCT 3D reconstructions. Syrenomelia is a
      condition not compatible with the normal life, however nine cases of "mermaid"
      survived to reconstructive surgery have been reported until now. In our report we
      also presented a case of survival baby girl affected by sirenomelia, before and
      after surgery, with correlative radiologic imaging findings. The most important
      characteristic that seems to allow survival of the affected individuals is the
      presence of one functional kidney, displaced in pelvis. As so dramatically tragic
      was the history of the Andersen Little Mermaid, so unattended pleasant would be
      the destiny of a modern mermaid, who can hope to finally marry her prince,
      without the risk to "loose her head", as the Copenhagen City's Symbol did in the
      past years, for a story beyond the Myth.

PMID- 16423485
TI  - Hydrophilic interaction liquid chromatography-tandem mass spectrometry for the
      determination of levofloxacin in human plasma.
AB  - A rapid, sensitive and selective hydrophilic interaction liquid chromatography
      tandem mass spectrometric (HILIC-MS/MS) method for the determination of
      levofloxacin in human plasma was developed. Levofloxacin and ciprofloxacin
      (internal standard) were extracted from human plasma with dichloromethane and
      analyzed on an Atlantis HILIC Silica column with the mobile phase of acetonitrile
      ammonium formate (100 mM, pH 6.5) (82:18 v/v). The analytes were detected using
      an electrospray ionization tandem mass spectrometry in the multiple-reaction
      monitoring mode. The standard curve was linear (r>0.999) over the concentration
      range of 10.0-5000 ng/ml. The lower limit of quantification for levofloxacin was
      10.0 ng/ml using 20 microl plasma sample. The coefficient of variation and
      relative error for intra- and inter-assay at four QC levels were 2.9-7.8% and 
      7.3% to -2.2%, respectively. The recoveries of levofloxacin and ciprofloxacin
      were 55.2% and 77.3%, respectively. This method was successfully applied to the
      pharmacokinetic study of levofloxacin in humans.

PMID- 16423486
TI  - Comparative assessment of kaempferitrin from medicinal extracts of Bauhinia
      forficata link.
AB  - The leaves of the pantropical genus Bauhinia (Fabaceae) are popularly known as
      cow's-paw or cow's hoof due to their unique characteristic bilobed aspect. The
      species Bauhinia forficata (Brazilian Orchid-tree) is widely used in folk
      medicine as an antidiabetic. This article deals with the quantitative analysis of
      kaempferitrin from B. forficata medicinal extract (aqueous and hydro alcoholic)
      using the LC method, and the comparison of kaempferitrin content in leaves
      collected from two different regions in the south Brazil. The total flavonoid
      content assessed by LC was also compared with the classical spectrophotometric
      determination. Kaempferitrin was found in different amounts, in samples from two
      geographical areas (Telemaco Borba/PR and Itajai/SC), for aqueous (368.68 and
      77.91 microg/mL) and hydro alcoholic extracts (1952.59 and 211.61 microg/mL),
      respectively. The method was subjected to recovery assay, to determine its
      accuracy. A marked difference in total flavonoid concentration was observed in
      relation to kaempferitrin content: 2759.95 and 2188.20 microg/mL for the
      fluidextract and 863.35 and 856.77 microg/mL for the aqueous extract (Telemaco
      Borba/PR and Itajai/SC). The spectrophotometric assay overestimated the total
      flavonoid content (3620 microg/mL) in relation to the LC assay.

PMID- 16423487
TI  - Disseminated Mycobacterium kansasii infection in an HIV-negative patient
      presenting with mimicking multiple bone metastases.
AB  - We report a patient with disseminated Mycobacterium kansasii infection, but with
      no underlying disease, presenting with mimicking multiple bone metastases with
      cancer of unknown primary site. Disseminated M. kansasii infection is rare in HIV
      negative patients without underlying diseases. This patient had disseminated M.
      kansasii infection manifested with vertebral osteomyelitis, sacroiliitis, psoas
      abscess, bone marrow granuloma, liver granuloma, and possible spleen abscesses.
      The clinical manifestations are described and discussed in details.

PMID- 16423488
TI  - A real-time polymerase chain reaction assay for detection of Pneumocystis from
      bronchoalveolar lavage fluid.
AB  - Pneumocystis jiroveci is an important cause of pneumonia in immunocompromised
      individuals. This organism cannot be cultured, and therefore, diagnosis relies on
      microscopic identification of the organism using stains or antibodies. Although
      simple, these tests are insensitive and require expertise for accurate
      interpretation. We developed a real-time polymerase chain reaction (PCR) assay
      that provides sensitive and objective detection of Pneumocystis from
      bronchoalveolar lavage fluid. Primers and fluorescence resonance energy transfer
      probes were developed that target the cdc2 gene of P. jiroveci. Assay sensitivity
      is 6 copies of target per microliter of sample. No cross-reactivity occurs with
      other pathogens, and the PCR assay has a 21% increase in clinical sensitivity as
      compared with Calcofluor white staining. The real-time PCR assay provides a
      sensitive, rapid, and objective method for the detection of Pneumocystis from
      bronchoalveolar lavage fluid.

PMID- 16423489
TI  - Species identification of corynebacteria by cellular fatty acid analysis.
AB  - We evaluated the usefulness of cellular fatty acid analysis for the
      identification of corynebacteria. Therefore, 219 well-characterized strains
      belonging to 21 Corynebacterium species were analyzed with the Sherlock System of
      MIDI (Newark, DE). Most Corynebacterium species have a qualitative different
      fatty acid profile. Corynebacterium coyleae (subgroup 1), Corynebacterium
      riegelii, Corynebacterium simulans, and Corynebacterium imitans differ only
      quantitatively. Corynebacterium afermentans afermentans and C. coyleae (subgroup
      2) have both a similar qualitative and quantitative profile. The commercially
      available database (CLIN 40, MIDI) identified only one third of the 219 strains
      correctly at the species level. We created a new database with these 219 strains.
      This new database was tested with 34 clinical isolates and could identify 29
      strains correctly. Strains that remained unidentified were 2 Corynebacterium
      aurimucosum (not included in our database), 1 C. afermentans afermentans, and 2
      Corynebacterium pseudodiphtheriticum. Cellular fatty acid analysis with a self
      created database can be used for the identification and differentiation of
      corynebacteria.

PMID- 16423490
TI  - Pharmacodynamic profiling of cefepime in plasma and cerebrospinal fluid of
      hospitalized patients with external ventriculostomies.
AB  - Population pharmacokinetic (PK) modeling and Monte Carlo simulation (MCS) were
      used to describe the pharmacodynamic profile of cefepime in the both plasma and
      cerebrospinal fluid (CSF). Plasma and CSF cefepime data were obtained from a PK
      study of 7 hospitalized patients with external ventricular drains. Concentration
      time profiles in plasma and CSF were modeled using a 3-compartment model with
      zero-order infusion and first-order elimination and transfer. Estimates of the PK
      parameters were identified in the Big Non Parametric Adaptive Grid with adaptive
      gamma (BigNPAG) program of Leary, Jelliffe, Schumitzky, and Van Guilder. MCS
      (10,000 subjects) was performed to estimate the probability of attaining the
      targets of free plasma concentration (20% protein binding) and total drug CSF
      concentration of 50-100% T>minimal inhibitory concentration (MIC) for MICs 0.06-8
      mg/L for cefepime 2 g, iv, every 8 h (0.5-h infusion); cefepime 2 g, iv, every 12
      h (0.5-h infusion); and cefepime 2 g (0.5-h infusion) once and 250 mg/h
      continuous infusion. After the Bayesian step, the observed-predicted regression
      and r(2) for plasma and CNS were as follows: plasma, observed=0.984 x
      predicted+2.570, r(2)=0.944; CSF, observed=0.785 x predicted+0.868, r(2)=0.821.
      The median penetration of cefepime as measured by AUC(CSF)/AUC(plasma) was 7.8%.
      In the MCS, the target attainment rates in plasma for 60-70% fT>MIC were high at
      each MIC value between 0.03 and 8 microg/mL for each regimen examined. In CSF,
      none of the regimens achieved 50-100% T>MIC for>80% of patients for MICs>0.5
      mg/L.

PMID- 16423492
TI  - Activity of gemifloxacin tested against Neisseria gonorrhoeae isolates including
      antimicrobial-resistant phenotypes.
AB  - The antigonococcal potency of gemifloxacin and 5 reference comparator
      antimicrobials was determined for a selected collection of gonococcal isolates.
      The 250 Neisseria gonorrhoeae strains were inclusive of (1) 50 historic strains
      from Japan with elevated fluoroquinolone minimal inhibitory concentration values
      (QRNG) and (2) 200 contemporary strains from clinical specimens in 2004 (176 from
      6 sentinel sites in the United States and 24 bacteremic isolates from the SENTRY
      Antimicrobial Surveillance Program). The rank order of potency of the tested
      antimicrobials for the entire collection was: ceftriaxone (MIC(90) = 0.06
      microg/mL) > gemifloxacin (1 microg/mL) > tetracycline (2 microg/mL) >
      ciprofloxacin = levofloxacin = penicillin (4 microg/mL). The activity of
      gemifloxacin was not affected by penicillinase production; however, its activity
      was decreased for penicillin-resistant strains. Cross-resistance between
      gemifloxacin and the older fluoroquinolones was present, and the gemifloxacin
      MIC90 value was higher for the ciprofloxacin-resistant strains compared with the
      ciprofloxacin-susceptible strains (2 versus 0.016 mug/mL, respectively). More
      than 20.0% of the recent clinical strains were resistant to penicillin,
      tetracycline, and ciprofloxacin with >30.0% of gonococci resistant to
      ciprofloxacin in Washington State and Hawaii. The historic QRNG strains from the
      Far East were predominantly of intermediate susceptibility (88.0%) to
      ciprofloxacin, with a gemifloxacin MIC90 value of only 0.25 microg/mL. The
      bacteremic gonococcal strains were exquisitely susceptible to the 3 quinolones
      tested (ciprofloxacin, levofloxacin, and gemifloxacin, MIC90 at < or = 0.03
      microg/mL) and ceftriaxone (MIC90 = 0.06 microg/mL). In summary, the potency of
      gemifloxacin was competitive and positioned between that of ceftriaxone and older
      quinolones or penicillin or tetracycline, irrespective of the gonococcal
      resistance phenotype. Gemifloxacin should be considered for further development
      as a therapeutic option to treat uncomplicated infections due to emerging strains
      resistant to penicillins, tetracycline, and some older fluoroquinolones.

PMID- 16423491
TI  - Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia
      coli and Klebsiella species as defined by CLSI reference methods: report from the
      SENTRY Antimicrobial Surveillance Program.
AB  - As extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae continue
      to emerge worldwide, selection of empiric treatment modalities is an increasing
      challenge. Data describing the clinical outcomes associated with different
      treatment regimens have been limited. Using data from centers with confirmed ESBL
      and non-ESBL-producing Escherichia coli and Klebsiella species isolates in North
      America, Latin America, and Europe, potential risk factors for the occurrence of
      invasive ESBL- and non-ESBL-producing Enterobacteriaceae infections and factors
      associated with clinical outcome were evaluated. Of the 175 cases considered
      evaluable, 77% were ESBL-producing organisms. Underlying comorbidities and
      potential risk factors were generally similar between ESBL and non-ESBL cases
      with a statistically greater proportion of ESBL cases requiring gastrostomy or
      jejunostomy tubes, ventilatory assistance, or care in the intensive care unit
      before culture (P<or=0.008). Among ESBL cases, carbapenem monotherapy and
      combination therapy were often selected for treatment (32.6% and 13.3%,
      respectively). Among non-ESBL cases, fluoroquinolones and beta-lactam/beta
      lactamase inhibitor combination agents accounted for the highest proportion of
      treatment regimens (25.0% and 22.5%, respectively), whereas cephalosporin
      monotherapy and combination therapy were each used as treatment for 10% of cases.
      Clinical success was similar between patients with ESBL and non-ESBL-producing
      isolates (83% and 80%, respectively). Although infections arising from E. coli
      and Klebsiella species are associated with significant mortality, ESBL production
      alone did not appear to be an independent risk factor for treatment failure.

PMID- 16423493
TI  - Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae
      strains from Italy: report from the SENTRY Antimicrobial Surveillance Program
      (2001-2004).
AB  - Fluoroquinolones are key antimicrobials in the treatment of more serious
      pneumococcal infections, especially for treating infections caused by penicillin
      resistant strains. Increased use of newer fluoroquinolones should be accompanied
      by greater surveillance efforts to monitor resistance development as well as
      clonal dissemination. Streptococcus pneumoniae (n=551) collected from 3 medical
      centers in Italy (Catania, Genoa, and Rome) over a period of 4 years (2001-2004)
      as part of the SENTRY Antimicrobial Surveillance Program were susceptibility
      tested against >30 antimicrobials using reference broth microdilution methods.
      Mutations in the quinolone resistance-determining region (QRDR) were
      characterized by PCR and sequencing of parC, parE, and gyrA. Epidemiological
      relationships among levofloxacin-resistant isolates were determined using
      ribotyping, PFGE, serotyping combined with antimicrobial resistance profiles
      augmented by QRDR mutation patterns. Eighty-three (15.1%) isolates showed reduced
      susceptibility to ciprofloxacin (MIC>or=4 microg/mL) and 31 (5.6%) were resistant
      to levofloxacin. In 2001, all pneumococcal isolates were susceptible to
      levofloxacin and resistance rapidly emerged in all 3 medical centers in 2002. The
      overall rates of levofloxacin resistance in 2002-2004 were the following: Catania
      10.9%, Genoa 3.3%, and Rome 6.5%. All resistant strains showed at least one
      mutation in parC and gyrA. Each isolate from Genoa with a unique resistance
      phenotype also showed distinct ribotype/PFGE, serotype, and QRDR mutation
      patterns. All isolates from Catania (n=19) showed an identical ribotype/PFGE
      pattern (333.3/A1); however, 3 distinct clusters could be identified based on
      further resistance phenotype, serotypes, and QRDR mutation pattern analysis. Two
      clusters were documented among isolates from Rome based on ribotype/PFGE. One
      isolate from Genoa shared ribotype/PFGE (333.3/A1) and serotype (9 not V) results
      with clusters from the other 2 institutions monitored, indicating clonal
      dissemination between the geographically diverse cities. In conclusion,
      fluoroquinolone resistance rates have increased among S. pneumoniae recovered in
      Italian medical centers evaluated by the SENTRY Program. Although resistance has
      emerged in many epidemiologically distinct strains, clonal dissemination seems to
      be a key contributing factor for increasing resistance to fluoroquinolones among
      pneumococci in this nation.

PMID- 16423494
TI  - The value of Gram staining of catheter segments for rapid detection of peripheral
      venous catheter infections.
AB  - Catheter-related bloodstream infections are common in hospitalized patients.
      Peripheral venous catheters (PVCs) are the most frequently used vascular access
      devices with usually low reported infection rates. We conducted a study to find
      the rate of PVC-related infections using semiquantitative (roll plate) and
      quantitative catheter culture techniques. We found significant growth in 9.5% of
      the PVCs by quantitative culture, which was predictive of a BSI in 43% of cases,
      which seems to be the major limitation of the method. We conclude that Gram stain
      is a fast and reliable diagnostic tool for rapid detection of PVC infection.

PMID- 16423495
TI  - Clinical evaluation of repetitive sequence-based polymerase chain reaction using
      the Diversi-Lab System for strain typing of vancomycin-resistant enterococci.
AB  - The reliability of the Diversi-Lab System, an automated method of microbial
      strain typing using repetitive sequence-based polymerase chain reaction (rep
      PCR), was evaluated by comparing results with those obtained by pulsed-field gel
      electrophoresis (PFGE). Ninety-five clinical isolates of vancomycin-resistant
      enterococci (VRE; 13 groups, 2-17 isolates per group) sent to Associated Regional
      and University Pathologists (ARUP) Laboratories for typing were tested by both
      methods. Rep-PCR and PFGE results were concordant for 83 isolates: all 32
      isolates in 6 of the groups and 51 of the 63 isolates in the other 7 groups.
      Clustering of the remaining 12 isolates differed. With the Diversi-Lab System,
      analysis is objective, and results are available in 4 h, compared with a more
      subjective analysis and a 2- to 3-day turnaround time for PFGE. The Diversi-Lab
      System may be a viable alternative to PFGE for typing VRE in clinical reference
      laboratories.

PMID- 16423496
TI  - Comparison of real-time polymerase chain reaction using the Smart Cycler and the
      Gen-Probe amplified Mycobacterium tuberculosis direct test for detection of M.
      tuberculosis complex in clinical specimens.
AB  - The performance of a real-time polymerase chain reaction (PCR) assay using the
      Smart Cycler instrument and a minor groove binding MGB Eclipse probe (Epoch
      Biosciences, Bothell, WA) for identification of Mycobacterium tuberculosis
      complex in acid-fast bacillus smear-positive and smear-negative clinical
      specimens was assessed by comparing results to the Amplified M. tuberculosis
      Direct Test (MTD) and mycobacterial culture plus clinical diagnosis. After
      initial testing, the overall sensitivity, specificity, and positive and negative
      predictive values of PCR for the 172 specimens submitted for mycobacterial
      culture were 86.3%, 100%, 100%, and 94.5%, respectively. These same values for
      MTD were 98.0%, 99.2%, 98.0%, and 99.2%. For 83 additional specimens, only MTD
      and PCR were performed; 5 specimens were positive and 78 were negative by both
      tests. The sensitivity of the PCR assay was improved by using different primers
      and probes. The time to a result for real-time PCR, starting with a
      decontaminated sample, was less than 3 h compared with 5-6 h for the MTD.

PMID- 16423497
TI  - Muscarinic acetylcholine receptor inhibition in transgenic Alzheimer-like Tg2576
      mice by scopolamine favours the amyloidogenic route of processing of amyloid
      precursor protein.
AB  - The molecular mechanisms of the interrelationship between cholinergic
      neurotransmission, processing of amyloid precursor protein (APP) and beta-amyloid
      (Abeta) production in vivo are still less understood. To reveal any effect of
      cholinergic dysfunction on APP processing in vivo, 11-month-old transgenic Tg2576
      mice with Abeta plaque pathology received intraperitoneal injections of
      scopolamine at a daily dosage of 2mg/kg body weight for 14 days in order to
      suppress cortical cholinergic transmission by chronic inhibition of muscarinic
      acetylcholine receptors. Scopolamine treatment of transgenic Tg2576 mice resulted
      in increased levels of fibrillar Abeta(1-40) and Abeta(1-42), while the soluble,
      SDS-extractable Abeta level remained unchanged as compared to vehicle-injected
      Tg2576 mice. alpha-Secretase activity determined in cortical tissue from
      scopolamine-treated Tg2576 mice was lower by about 30% as compared to that
      assayed in control mice, while beta-secretase activity and BACE1 protein
      expression appeared unaffected by scopolamine treatment. The amount of sAPPalpha,
      the product secreted by alpha-secretase-mediated APP cleavage, and the
      unprocessed APP were assayed in the soluble and membrane fraction, respectively,
      of cortical tissue preparations from treated and control mice by Western
      blotting. Using the anti antibody 6E10 which specifically labels human sAPPalpha
      and full length APP in transgenic Tg2576, an enhanced APP level was detected in
      the membrane fraction from treated mice as compared to controls, while in the
      soluble fraction scopolamine treatment did not affect the protein level of
      sAPPalpha. These data indicate an accumulation of APP in cortical membrane
      fraction in scopolamine-treated Tg2576 mice presumably due to the decreased level
      of alpha-secretase-mediated APP cleavage, and further suggest that chronic
      suppression of cortical muscarinic cholinergic transmission may alter the balance
      between alpha- and beta-secretory APP processing by favouring the amyloidogenic
      route.

PMID- 16423498
TI  - Developmental and amyloid plaque-related changes in cerebral cortical capillaries
      in transgenic Tg2576 Alzheimer mice.
AB  - There is experimental evidence that cerebral perfusion is decreased during aging
      and in Alzheimer's disease. To characterize the temporal relationship between
      amyloid deposition, plaque size and cerebrovascular abnormalities, a
      semiquantitative immunohistochemical study was performed in transgenic Tg2576
      mice that express the Swedish double mutation of human amyloid precursor protein
      (APP) and progressively develop Alzheimer-like beta-amyloid deposits. Cortical
      cryocut sections, obtained from mice at ages ranging between 4 and 18 months,
      were immunostained to label glucose transporter type 1 (GLUT1), a marker of
      vascular endothelial cells, and thioflavine-S to visualize plaques. Regardless of
      age and transgene, a laminar distribution of capillaries was observed being
      highest in cortical layers IV and V. The density of microvessels estimated in
      cortical regions with high plaque load was found to be significantly lower as
      compared to areas with low plaque load. Around large thioflavine-S-positive
      senile plaques the capillary density was low, while diffuse plaques demonstrated
      a close association of capillaries with no signs of any damage. The data suggest
      that amyloid plaque deposition differentially affects the cerebrovascular system
      in an age- and plaque type-related manner, and provide further evidence that beta
      amyloid, in addition to its well-described neurotoxic effects, may also
      contribute to neuronal dysfunction through its actions on the cerebrovasculature.

PMID- 16423499
TI  - Ectopic insulin-like growth factor I expression in avian skeletal muscle prevents
      expression of CMD4, a novel inhibitor of differentiation.
AB  - Embryonic chick skeletal muscle undergoes profound hypertrophy in response to
      ectopic IGF-I resulting in two- to three-fold increase in total muscle mass. IGF
      I likely causes several changes in gene expression profiles to elicit the robust
      effect. To identify genes differentially affected by IGF-I, total RNA was
      isolated from the hindlimbs of chick embryos infected with RCAS or RCAS-IGF-I and
      used in a subtractive library screen. CMD4 was identified as a novel, avian
      specific gene expressed in muscle. In situ mRNA analysis reveals that the gene
      product is expressed in multiple tissues including skeletal muscle. Ectopic
      expression of IGF-I within the hindlimb results in a reduction in CMD4 mRNA to
      levels below conventional detection limits. A chimeric CMD4-yellow fluorescent
      protein (CMD4-YFP) demonstrates an indiscriminant localization pattern throughout
      the cytoplasm and nucleus of myoblasts. By contrast to control C2C12 myoblasts, a
      stable muscle cell line that expresses CMD4-YFP (C2C12-CMD4-YFP) is unable to
      form the large multinucleated cells characteristic of mature myofibers. The
      differentiation defective myoblasts do not express myosin heavy chain but the
      relative amounts of myogenin, desmin and troponin proteins do not differ from
      controls. The transcriptional activity of the myogenic regulatory factors (MRFs)
      remains unchanged by CMD4 expression. We report the identification of an IGF-I
      inhibited gene present in skeletal muscle. While the mechanism of CMD4-mediated
      inhibition of muscle development remains elusive, we propose that loss of CMD4
      gene expression may be required for optimal muscle hypertrophy in the chick
      embryo.

PMID- 16423500
TI  - Milk production correlates negatively with plasma levels of pregnancy-associated
      glycoprotein (PAG) during the early fetal period in high producing dairy cows
      with live fetuses.
AB  - This study was designed to establish possible factors affecting plasma pregnancy
      associated glycoprotein (PAG) concentrations during early pregnancy in high
      producing dairy cows with live fetuses. Blood samples were obtained on days 35,
      42, 49, 56 and 63 of gestation from 80 lactating cows in two herds carrying live
      fetuses. Radioimmunoassay systems were used to determine PAG (RIA-497 and RIA
      706) and progesterone concentrations. We evaluated the effects on PAG
      concentrations of herd, lactation number, sire of fetus, day of gestation, fetus
      number, plasma progesterone and milk production at each time point established,
      along with possible paired interactions. Mean milk production per cow approached
      41kg during the study period. PAG concentrations were not affected by herd,
      lactation number or plasma progesterone concentration. Significant positive
      effects on PAG concentrations were shown by the gestation day, and the
      interaction between day of gestation and twin pregnancy. Significant differences
      between bulls and a significant negative correlation between milk production and
      PAG values on day 63 of pregnancy were also detected. Proportions of blood
      samples showing undetectable PAG levels and false negative diagnoses throughout
      the study period were significantly higher (P<0.001) using the RIA-497 system
      (2.5% and 5.3%, respectively) compared to RIA-706 (0% and 0.8%, respectively).
      Our findings suggest that PAG concentrations during the early fetal period are
      related to the day of gestation, milk production, number of fetuses and sire of
      fetus in high producing dairy cows. Under our working conditions, the RIA-706
      method was better at detecting plasma PAG molecules than the RIA-497 system.

PMID- 16423501
TI  - Reduction in channel catfish hepatic growth hormone receptor expression in
      response to food deprivation and exogenous cortisol.
AB  - The objective of this study was to assess the effects of food deprivation and
      exogenous cortisol administration on somatic growth of channel catfish, Ictalurus
      punctatus, and examine the resultant changes in circulating insulin-like growth
      factor-I (IGF-I) concentrations and growth hormone receptor (GHR) gene
      expression. Integral to this objective, we report the isolation, sequence, and
      characterization of channel catfish GHR. Sequence analysis and characterization
      results indicate sequence identity and tissue distribution similar to GHRs in
      other teleost fish and several functional characteristics conserved in known
      vertebrate GHRs. The effects of food deprivation and dietary exogenous cortisol
      administration were assessed as part of a 4-week study. Growth was significantly
      reduced after 4 weeks in cortisol-fed fish compared to fed-control fish, and
      fasting resulted in weight loss. At the end of the 4-week study, both IGF-I
      plasma concentrations and hepatic GHR mRNA abundance were significantly reduced
      in fasted and cortisol-fed catfish. Levels of hepatic GHR mRNA were positively
      correlated to circulating IGF-I levels. These results suggest that a reduction in
      hepatic GHR gene expression might serve as a mechanism for the reduction of
      circulating IGF-I and growth in channel catfish during periods of food
      deprivation and stress.

PMID- 16423502
TI  - Propagation and control of stochastic signals through universal learning
      networks.
AB  - The way of propagating and control of stochastic signals through Universal
      Learning Networks (ULNs) and its applications are proposed. ULNs have been
      already developed to form a superset of neural networks and have been applied as
      a universal framework for modeling and control of non-linear large-scale complex
      systems. However, the ULNs cannot deal with stochastic variables. Deterministic
      signals can be propagated through a ULN, but the ULN does not provide any
      stochastic characteristics of the signals propagating through it. The proposed
      method named Probabilistic Universal Learning Networks (PrULNs) can process
      stochastic variables and can train network parameters so that the signals behave
      with the pre-specified stochastic properties. As examples of applications of the
      proposed method, control and identification of non-linear dynamic systems with
      noises are studied, and it is shown that the method are useful for dealing with
      the control and identification of the non-linear stochastic systems contaminated
      with noises.

PMID- 16423503
TI  - Oral lichen planus and dental implants. Report of 3 cases.
AB  - Oral lichen planus (OLP) is generally considered to be a contraindication for the
      placement of dental implants. This report describes 3 female patients in whom
      implants were installed, either before OLP developed or thereafter. OLP in all 3
      patients was asymptomatic and mostly of the atrophic or mixed atrophic and
      reticular type. The implants were in place between 15 years and 3 months. Bone
      resorption around the implants in all 3 patients was on average 3-4 mm. All
      implants were functioning well. Patients with OLP of the asymptomatic type
      involving the gingiva may be treated with dental implants, however, strict follow
      up is recommended.

PMID- 16423504
TI  - Coroner and medical examiner documentation of sudden unexplained deaths in
      epilepsy.
AB  - BACKGROUND: Prevalence data for sudden unexplained death in epilepsy (SUDEP) are
      hampered by its underuse as a final diagnosis on death certificates in
      appropriate cases. Few data exist about how coroners (COs) and medical examiners
      (MEs) in the United States use the diagnosis of SUDEP. METHODS: A survey
      instrument that addressed demographics, professional background, annual cases of
      epilepsy, seizure history, percentage of post-mortem examinations, cause of
      death, and use of SUDEP as a diagnosis was sent to all COs and MEs in the United
      States. Unadjusted comparisons between categorical variables used chi2 tests. A
      multiple regression model examined the odds of respondents considering SUDEP to
      be a valid diagnosis. RESULTS: Of 2995 surveys, 80.7% went to COs and 19.3% to
      MEs. The response rate was 15.9% for COs and 21.8% for MEs. Acknowledgment of
      SUDEP as a valid entity was greatest among pathologists (83.5%) versus other
      physicians and non-physicians (P< .001) and correlated with higher autopsy rates
      and seeing more cases of epilepsy. In actual practice, SUDEP was not used
      routinely as a death certificate diagnosis in most cases with no cause of death
      found at autopsy by any group in the survey regardless of title, educational
      background, location, autopsy rate, or number of seizure cases seen annually.
      CONCLUSIONS: SUDEP appears to be an underused final diagnosis by COs and MEs
      throughout the United States. There is a need to educate officials at all levels
      about this diagnosis in persons who have epilepsy with no other cause of death.

PMID- 16423505
TI  - Measuring remission in schizophrenia: response to Sethuraman et al., 2005.

PMID- 16423506
TI  - Effect of liposome encapsulation of tea catechins on their accumulation in basal
      cell carcinomas.
AB  - BACKGROUND: (-)-Epigallocatechin gallate (EGCG), the main active polyphenol in
      green tea, is associated with antioxidant and anticancer activities. OBJECTIVE:
      The aim of this study was to evaluate the feasibility of using liposomes for
      intratumor distribution of EGCG and its derivative, (+)-catechin. METHOD:
      Liposomes containing egg phosphatidylcholine, cholesterol, or anionic surfactant
      in the presence of 15% ethanol were prepared. The physicochemical characteristics
      including vesicle size, zeta potential, drug entrapment, and drug release of
      liposomal formulations were determined. The liposomes containing EGCG were
      injected into basal cell carcinomas (BCCs), melanomas, and colon tumors to
      examine the tumor uptake of the drug. Liposomes were also incubated with a given
      number of BCC cells, and the cell viability was estimated. RESULT: Almost no drug
      molecules were observed when free EGCG was administered to BCCs. EGCG
      encapsulated in liposomes with deoxycholic acid (DA) and ethanol increased drug
      deposition by 20-fold as compared to the free form. The larger vesicle size of
      this formulation was suggested to be the predominant factor governing this
      enhancement. The liposomes without ethanol showed low or negligible enhancement
      on EGCG uptake in BCCs. Liposomes protected EGCG from degradation, resulting in
      the induction of greater BCC death compared to that by free EGCG at lower
      concentrations. CONCLUSION: These results suggest that the intratumor injection
      of liposomes containing EGCG with moderate modification is an effective approach
      for increasing EGCG deposition in BCCs.

PMID- 16423507
TI  - Anti-inflammatory activity in skin by biomimetic of Evodia rutaecarpa extract
      from traditional Chinese medicine.
AB  - BACKGROUND: Wu-Zhu-Yu, is an extract prepared from the small berry fruit of
      Evodia rutaecarpa and is reported to have anti-inflammatory and anti-nociceptic
      activity. Methyl nicotinate (MN) is known to induce the release of PGD(2)
      resulting in localized erythema within 30 min after topical application to human
      skin. OBJECTIVE: The purpose of this study was to determine if a defined
      biomimetic mixture of components of Evodia fruit extract inhibit inflammation in
      human cells and skin. METHODS: In order to control the potency of the test
      article, we prepared a defined biomimetic mixture of synthetic and natural forms
      of the active components of Evodia fruit extract, containing rutaecarpine,
      dehydroevodiamine, and evodin. This was tested for anti-inflammatory activity in
      UVB-irradiated cultured cells and in the MN model of micro-inflammation in human
      skin. RESULTS: This Evodia biomimetic mixture was a potent inhibitor of UVB
      induced PGE(2) released by keratinocytes in culture. We found that MN also
      induces release of nitric oxide from cultured keratinocytes and microvascular
      endothelial cells. Twice daily application of 0.1-1% Evodia biomimetic mixture
      for 2 weeks significantly inhibited erythema after a MN challenge. A single
      application of 1% Evodia biomimetic mixture also significantly inhibited MN
      induced erythema when applied at 60 min before, or within 5 min after MN
      exposure. The Evodia biomimetic mixture was significantly more effective at
      inhibiting erythema than bisabolol, the active component of chamomile.
      CONCLUSIONS: These results demonstrate that compounds found in E. rutaecarpa
      (including the indole quinazoline alkaloids) have powerful anti-inflammatory
      activity when applied topically to human skin.

PMID- 16423508
TI  - Systemic immunomodulatory effects of Polypodium leucotomos as an adjuvant to PUVA
      therapy in generalized vitiligo: A pilot study.

PMID- 16423509
TI  - Community-acquired methicillin-resistant Staphylococcus aureus infections.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) should no longer be regarded
      as a strictly nosocomial pathogen. During the past decade, community-acquired
      MRSA (CA-MRSA) infections among young persons without healthcare-associated (HCA)
      risk factors have emerged in several areas worldwide. These infections are caused
      by strains that almost exclusively carry the staphylococcal cassette chromosome
      mec type IV element and the Panton-Valentine leukocidin genes and, unlike HCA
      MRSA strains, are not multiresistant. Although the majority of CA-MRSA infections
      are mild skin and soft tissue infections, severe life-threatening cases of
      necrotizing pneumonia, necrotizing fasciitis, myonecrosis and sepsis have been
      reported. Clindamycin is an effective agent for skin and soft tissue infections,
      however attention should be paid to the possibility of the emergence of
      resistance during treatment in strains with the macrolide, lincosamide and group
      B streptogramin (MLS(B))-inducible resistance phenotype. For patients with
      invasive infections that may be caused be CA-MRSA, vancomycin, teicoplanin and
      linezolid represent appropriate empirical therapeutic options.

PMID- 16423510
TI  - Newly developed colorimetric drug screening assay for Bacillus anthracis.

PMID- 16423511
TI  - Evidence for tetracycline resistance determinant tet(M) allele replacement in a
      Streptococcus pneumoniae population of limited geographical origin.
AB  - A collection of 185 Streptococcus pneumoniae isolates was tested for their
      susceptibility to antipneumococcal drugs, with a focus on the distribution of
      tetracycline resistance determinants tet(M) and tet(O). Resistance patterns were
      compared with established correlates of multidrug resistance, and tetracycline
      resistant isolates were tested for clonality and allelic variation within tet(M).
      Resistance to tetracyclines, penicillins and macrolides were all strongly related
      to multidrug resistance. Over one-quarter of the strains were tetracycline
      resistant, all via the tet(M)-mediated mechanism. Restriction fragment length
      polymorphism analysis revealed a high degree of allelic variation within tet(M)
      and gave evidence of a clonal and horizontal spread of selected alleles. A tet(M)
      variant that emerged with the onset of epidemic multidrug-resistant strains was
      replacing old alleles in the population.

PMID- 16423512
TI  - Regulation of decapentaplegic expression during Drosophila wing veins pupal
      development.
AB  - The differentiation of veins in the Drosophila wing relies on localised
      expression of decapentaplegic (dpp) in pro-vein territories during pupal
      development. The expression of dpp in the pupal veins requires the integrity of
      the shortvein region (shv), localised 5' to the coding region. It is likely that
      this DNA integrates positive and negative regulatory signals directing dpp
      transcription during pupal development. Here, we identify a minimal 0.9 kb
      fragment giving localised expression in the vein L5 and a 0.5 kb fragment giving
      expression in all longitudinal veins. Using a combination of in vivo expression
      of reporter genes regulated by shv sequences, in vitro binding assays and
      sequence comparisons between the shv region of different Drosophila species, we
      found binding sites for the vein-specific transciption factors Araucan, Knirps
      and Ventral veinless, as well as binding sites for the Dpp pathway effectors Mad
      and Med. We conclude that conserved vein-specific enhancers regulated by
      transcription factors expressed in individual veins collaborate with general vein
      and intervein regulators to establish and maintain the expression of dpp confined
      to the veins during pupal development.

PMID- 16423513
TI  - Zn2+ release from zinc and zinc oxide particles in simulated uterine solution.
AB  - Zn(2+) release from Zn and ZnO particles with different sizes in simulated
      uterine solution were investigated by absorbance measurements. The effects of pH
      and human serum albumin (HSA) on Zn(2+) release were also studied. The morphology
      of Zn and ZnO particles was observed by scanning electron microscopy, and the
      corrosion products of zinc nanoparticles were analyzed by XRD. The results
      indicate that the maximum release ratios of Zn(2+) from Zn and ZnO nanoparticles
      are higher than those from Zn and ZnO microparticles. Zn(2+) release ratio
      depends not only on the pH of the simulated uterine solution but also the
      presence of human serum albumin. It decreases as the pH of the uterine solution
      increases. The trends of Zn(2+) release ratios are almost the opposite for
      solutions with and without HSA. XRD analysis results indicate that zinc oxide is
      the main corrosion product of zinc particles.

PMID- 16423514
TI  - Effect of monascus pigment derivatives on the electrophoretic mobility of
      bacteria, and the cell adsorption and antibacterial activities of pigments.
AB  - Various amino acid derivatives of monascus pigments were synthesized. The effects
      of pigment derivatives on the pigment adsorption ratio, electrophoretic mobility
      (EPM) of bacterial cells, and antibacterial activity were investigated under
      varying conditions of pigment type, pigment concentration, pH, and ionic
      strength. Two hydrophobic and two hydrophilic derivatives were selected as model
      pigments. There was a close relationship between the antimicrobial activity and
      the pigment adsorption ratio. Against Escherichia coli, the hydrophobic L-Tyr and
      L-Phe derivatives (log P = 3.18 and 3.57) exhibited high antimicrobial activities
      (MIC = 8 and 16 mg/L) and high cellular adsorption ratios (9.6 and 10.9 mg/L).
      The hydrophilic L-Glu and L-Asn derivatives (log P = 1.40 and 0.47) exhibited low
      activities (MIC = 64 and 128 mg/L) and low adsorption ratios (4.7 and 4.0 mg/L).
      The electrophoretic mobility of 11 different bacteria varied between -1.93 x 10(
      8) and -1.19 x 10(-8) m(2) V(-1) s(-1) regardless of Gram(+) or Gram(-). The L
      Phe derivative showed low MIC values (high antimicrobial activities) against
      bacteria with a high electrophoretic mobility. A positive linearity between the
      pigment adsorption ratio and the electrophoretic mobility was established. When
      the four pigment derivatives were added to E. coli solutions, the electrophoretic
      mobility of cells in all cases sharply increased with an increasing pigment
      concentration. The mobility value was high for hydrophobic pigment derivatives in
      descending order of L-Phe (0.8 x 10(-8) m(2) V(-1) s(-1)), L-Tyr (0.68 x 10(-8)
      m(2) V(-1) s(-1)), L-Glu (0.46 x 10(-8) m(2) V(-1) s(-1)), and L-Asn (0.44 x 10(
      8) m(2) V(-1) s(-1)). Additional adsorption of the hydrophobic derivatives
      probably occurred due to a hydrophobic interaction between the pigment and the
      pigment-coated cells. The electrophoretic mobility decreased gradually with an
      increasing pH and/or ionic strength with both addition and no addition of the
      pigment derivatives. The pattern of change of the pigment adsorption ratio under
      varying pH and/or ionic strength values was similar to the pattern for
      electrophoretic mobility.

PMID- 16423515
TI  - [Clinical guidelines for the screening and the diagnosis of autism and pervasive
      developmental disorders].
AB  - Autism is the best defined category among PDD. Its high prevalence, its onset in
      very young children and its persistence in adulthood arise many questions about
      early screening and early diagnosis. The aim of the study was to identify
      professional best practices about screening and diagnosis of autism in order to
      propose clinical guidelines and actions for the future. Scientific experts and
      parents take part to this procedure. Literature and previous guidelines were
      analyzed, experts in various fields were interviewed, a national study about the
      medical practices of the diagnosis of autism was made and questionnaires were
      send to 1600 psychiatrists and pediatricians. Guidelines built around 2 levels
      were proposed about screening and diagnosis. CONCLUSION: Diagnosis needs a
      multidisciplinary approach, validated instruments and more communication between
      professionals and parents. Finally one of the more important aims of the
      diagnosis of autism is to facilitate intervention program.

PMID- 16423516
TI  - [Adolescent contraception: the great paradox].

PMID- 16423517
TI  - [Metered-dose inhaler with spacer vs nebulization for severe and potentially
      severe acute asthma treatment in the pediatric emergency department].
AB  - OBJECTIVE: To compare treatment with beta 2 agonist delivered either by a spacer
      device or a nebulizer in children with severe or potentially severe acute asthma.
      METHODS: In this randomized trial, children 4 to 15 years, cared for in the
      emergency department for severe or potentially severe acute asthma, received 6
      times either nebulizations of salbutamol (0.15mg/kg) or puffs of a beta 2 agonist
      (salbutamol 50 microg/kg or terbutaline 125 microg/kg). The primary outcome was
      the hospitalization rate. Secondary outcomes included percentage improvement in
      Bishop score, in PEF, SaO(2), respiratory and heart rates, side effects, length
      of stay and relapses 10 and 30 days later. RESULTS: Groups did not differ for
      baseline data. There were no significant differences between the 2 groups
      (nebulizer N=40, spacer N=39) for baseline characteristics before emergency
      department consultation except for length of acute asthma in the spacer group.
      Clinical evolution after treatment, hospitalization rate, relapse were similar
      including the more severe subgroup. In the spacer group, tachycardia was less
      frequent (P<0.02). The overall length of stay in the emergency department was
      significantly shorter (148+/-20 vs 108+/-13 min, P<10(-9)). CONCLUSIONS: The
      administration of beta 2 agonist using a metered-dose inhaler with spacer is an
      effective alternative to nebulizers for the treatment of children with severe or
      potentially severe acute asthma in the emergency department. Time gained can be
      used for asthma education.

PMID- 16423519
TI  - The efficacy of St. John's Wort in patients with minor depressive symptoms or
      dysthymia--a double-blind placebo-controlled study.
AB  - INTRODUCTION: We studied the efficacy of St. John's Wort compared with placebo in
      patients with minor depressive symptoms or dysthymia, with the main focus on
      which diagnostic entities are optimally amenable to treatment with two different
      doses of Hypericum, and which are not. METHODS: One hundred and fifty patients,
      25-70 years old, meeting ICD-10 criteria for mild or moderately severe depressed
      episodes or with dysthymia, and having a 17-item Hamilton Depression Scale for
      Depression (HAM-D) total score between 7 and 17, were randomly assigned to an
      extract. The extract, PM235, manufactured by Cederroth International AB, Sweden,
      was given t.i.d. in a lower (0.12% hypericine) or a higher (0.18% hypericine)
      formulation, based on 270mg extractions or identical placebo. Clinical response
      was defined by HAM-D as a 50% reduction and/or a score 7. The Beck Depression
      Inventory (BDI) and Visual Analog Scales (VAS) were used as secondary efficacy
      parameters. Measures were conducted at screening, baseline, and after 3 and 6
      weeks of treatment. RESULTS: We found a large discrepancy in response between
      dysthymic and non-dysthymics, the latter seemingly more sensitive to Hypericum.
      HAM-D showed tendency but no significance toward a more frequent improvement of
      the non-dysthymics treated with Hypericum (p=0.057). BDI criteria showed
      significance (p=0.045) for both doses of Hypericum compared to placebo. Pooling
      high- and low-dose groups together, a significant reduction for HAM-D7 and BDI
      criteria was found among non-dysthymic patients (p=0.03). Significant improvement
      in response to Hypericum was found in symptoms reflected by VAS - again only in
      non-dysthymic patients (p=0.041). DISCUSSION: We observed, a tendency toward a
      more frequent significant improvement of the non-dysthymic patient treated with
      PM235, though this did not reach the level of statistical significance. In a
      secondary analysis, pooling both hypericine-treated groups concluded that
      Hypericum has a clinical significant effect in minor depressed patients with HAM
      D up to 17. This finding was significant only in non-dysthymic patients.

PMID- 16423518
TI  - [Ataxia-telangiectasia: a review].
AB  - Ataxia-telangiectasia (AT) is an autosomal recessive inherited disease caused by
      mutational inactivation of the ATM gene. It is a multisystemic disease,
      characterized by progressive neurological dysfunction, especially in the
      cerebellum, oculo-cutaneous telangiectasia, immunodeficiency, recurrent sino
      pulmonary infections and high incidence of neoplasms. The responsible gene, ATM,
      encodes a large protein that belongs to a family of protein kinases with a
      phosphatidylinositol 3-kinase (Pi3K) domain. ATM is a key regulator of cell cycle
      checkpoints that causes DNA repair or apoptosis. Several studies report ATM
      function in target cells (such as neurons, fibroblast, endothelium, germ cells,
      lymphocytes). The pleiotropic phenotypes of AT reflect the multifaceted
      activities of ATM protein. In nucleus (lymphocytes, fibroblasts, germ cells) ATM
      is involved in regulation of cell-cycle checkpoints; in cytoplasm ATM regulates
      redox state (neurons).

PMID- 16423520
TI  - Inhibitory effects of ethyl acetate extract of Cordyceps sinensis mycelium on
      various cancer cells in culture and B16 melanoma in C57BL/6 mice.
AB  - The cultivated mycelium of a Cordyceps sinensis (Cs) fungus was sequentially
      extracted by petroleum ether (PE), ethyl acetate (EtOAc), ethanol (EtOH) and hot
      water. All solvent extracts except hot water extract showed a significant and
      dose-dependent inhibitory effect on the proliferation of four cancer cell lines,
      MCF-7 breast cancer, B16 mouse melanoma, HL-60 human premyelocytic leukemia and
      HepG2 human hepatocellular carcinoma, with IC(50) values below 132 microg/ml. The
      EtOAc extract, in particular, had the most potent effect against all four cancer
      cell lines, with IC(50) between 12 microg/ml (on B16) and 45 microg/ml (on MCF
      7). In contrast, it had much lower cytotoxicity against normal mouse bone marrow
      cells. The EtOAc extract contained carbohydrates, adenosine, ergosterol and trace
      amount of cordycepin, of which ergosterol and related compounds were identified
      as a major class of active constituents contributing to the in vitro
      cytotoxicity. In an animal test, the EtOAc extract showed significant inhibiting
      effect on B16-induced melanoma in C57BL/6 mice, causing about 60% decrease of
      tumor size over 27 days. Our results suggest that the EtOAc extract of Cs fungal
      mycelium has strong anti-tumor activity and is a potential source of natural anti
      tumor products.

PMID- 16423521
TI  - Detection of Bacillus anthracis spores and a model protein using PEMC sensors in
      a flow cell at 1 mL/min.
AB  - Piezoelectric-excited millimeter-sized cantilever (PEMC) sensors of 4mm(2)
      sensing area were immobilized with antibody specific to Bacillus anthracis (anti
      BA) spores or bovine serum albumin (anti-BSA). Detection of pathogen (Bacillus
      anthracis (BA) at 300 spores/mL) and BSA (1 mg/mL) were investigated under both
      stagnant and flow conditions. Two flow cell designs were evaluated by
      characterizing flow-induced resonant frequency shifts. One of the flow cells
      labeled SFC-2 (hold-up volume of 0.3 mL), showed small fluctuations (+/-20 Hz)
      around a common resonant frequency response of 217 Hz in the flow rate range of 1
      17 mL/min. The total resonant frequency change obtained for the binding of 300
      spores/mL in 1h was 90+/-5 Hz (n=2), and 162+/-10 Hz (n=2) under stagnant and
      flow conditions, respectively. Binding of antibodies, anti-BA and anti-BSA, were
      more rapid under flow than under stagnant conditions. The sensor was repeatedly
      exposed to BSA with an intermediate release step. The first and second responses
      to BSA were nearly identical. The total resonant frequency response to BSA was
      388+/-10 (n=2) Hz under flow conditions. Kinetic analysis is carried out to
      quantify the effect of flow rate on antibody immobilization and the two types of
      detection experiments.

PMID- 16423522
TI  - 13C-Labelling of lipids to investigate microbial communities in the environment.
AB  - The introduction of (13)C-labelled substrates to soils, sediments or cultures
      followed by (13)C analysis of phospholipid fatty acids (PLFAs) provides
      quantitative and chemotaxonomic information for the groups of microorganisms
      utilizing a given substrate. Gas chromatography-combustion-isotope ratio mass
      spectrometry has provided the high precision necessary to measure small isotopic
      changes (differences in the relative abundances of (13)C to (12)C expressed as
      delta(13)C values) for nanogram amounts of individual compounds, such as
      microbial PLFAs. This methodology constitutes a powerful new culture-independent
      method for investigating microbial communities in the environment. The
      information obtained is highly complementary to that obtained from gene-probe
      based methods, and considerable possibilities exist to extend this methodology to
      include other biochemical components of microorganisms.

PMID- 16423524
TI  - Development.

PMID- 16423525
TI  - The changing landscape of protein allostery.
AB  - It is becoming increasingly clear that the fundamental capacity to undergo
      conformational change in response to ligand binding is intrinsic to proteins.
      This property confers on proteins the ability to be allosterically modulated in
      order to shift substrate binding affinities, alter enzymatic activity or regulate
      protein-protein interaction. How this allosteric modulation occurs--the pathways
      of communication, the shifting of conformational ensembles and the altered
      molecular dynamics--has received considerable attention during the past two
      years. Recent progress has helped outline the molecular origins of allostery in
      proteins as diverse as Hsp70 molecular chaperones and signal integrating
      proteins, such as WASP. In addition, allosteric properties have been successfully
      engineered into proteins for drug design or the development of novel biosensors.
      Methodological advances have provided exciting prospects for new insights and new
      biological roles of allosteric systems have been uncovered.

PMID- 16423526
TI  - Amplitude threshold criteria improve surface electrode specificity during walking
      and functional movements.
AB  - Contamination of electromyographic (EMG) data due to crosstalk in recordings from
      surface electrodes can lead to misinterpretation of results. The purpose of this
      study was to determine if removing a portion of the EMG signal normalized to a
      maximum voluntary contraction (MVC) would improve the specificity of surface
      electrode recordings. We hypothesized that setting an amplitude threshold to
      define when a muscle was active would remove that part of the myoelectric signal
      most likely to include crosstalk, without affecting the intensity or the onset
      and cessation times. Surface and intramuscular electrodes recorded signals from
      the same muscles of adults performing cyclic ankle movements and walking at self
      selected speeds. Signals identified as crosstalk were eliminated when 15% and 18%
      of the amplitude of the normalized signal was removed and muscle timing or
      intensity was not significantly changed in most cases.

PMID- 16423527
TI  - Electron energy loss spectra near structural defects in TiN and TiC.
AB  - In this study, we use first principles multiple scattering calculations on atomic
      clusters to show how the carbon and nitrogen K-edge fine structures are modified
      in the vicinity of structural defects in TiN and TiC. Changes in the electron
      energy loss spectra are due to changes in the atomic structure of the first
      atomic shells around the absorbing atom. Two different kinds of defects, which
      both modify the structure of these atomic shells, are investigated here. In a
      first part, we describe a method which correctly takes into account the
      statistical spatial distribution of nitrogen vacancies in a TiN cluster. We study
      the influence of vacancy concentration on the shape of the nitrogen K-edge
      spectra and we find that vacancies mainly affect the height of the second peak of
      the spectra. This peak decreases when the number of vacancies in the second
      nitrogen shell increases. In a second part, we study the carbon K-edge spectrum
      modification near stacking faults in TiC. Two different stacking faults are
      studied. These two-dimensional defects are responsible for changes in the
      position of the carbon as well as titanium atoms of the atomic shells centered on
      the absorbing carbon atom. The shape of the spectra is strongly modified near the
      stacking faults and several peaks are affected by these modifications. We show
      that these fine structure modifications only concern the very first carbon atomic
      layers near the two-dimensional defects.

PMID- 16423529
TI  - Dermoid cyst of the tongue: an association of dermoid cyst with bronchogenic
      epithelium.
AB  - A congenital dermoid together with a bronchogenic cyst of the tongue is extremely
      rare. The diagnosis made in this case of a 1-year-old boy was "teratoid cyst of
      the tongue". A surgical exploration was performed under general anaesthesia via a
      midline sagittal glossotomy. The tumour was completely dissected and excised, the
      microscopical examination of the surgical specimen revealed multiple cystic
      cavities lined by a keratinized squamous epithelium with skin appendages and
      fatty tissue. Others were composed of cylindrical, ciliated epithelial cells of
      respiratory type. This is the third reported case in the world literature. All
      cases were reviewed and compared with this case.

PMID- 16423528
TI  - Lysosomal proteases are involved in generation of N-terminal huntingtin
      fragments.
AB  - N-terminal mutant huntingtin (N-mhtt) fragments form inclusions and cause cell
      death in vitro. Mutant htt expression stimulates autophagy and increases levels
      of lysosomal proteases. Here, we show that lysosomal proteases, cathepsins D, B
      and L, affected mhtt processing and levels of cleavage products (cp) known as A
      and B, which form inclusions. Adding inhibitors of cathepsin D, B and L to clonal
      striatal cells reduced mhtt, especially mhtt fragment cp A. Mutant htt fully
      degraded in cathepsin-L-treated lysates but formed stable N-mhtt fragments upon
      exposure to cathepsin D. Mutagenesis analysis of htt cDNA suggested that
      cathepsin D and the protease for cp A may cleave htt in the same region. Brain
      lysates from HD knock-in mice expressed N-mhtt fragments that accumulated with
      cathepsin D treatment and declined with aspartyl protease inhibition. Findings
      implicate lysosomal proteases in formation of N-mhtt fragments and clearance of
      mhtt.

PMID- 16423530
TI  - A clinical study on ankylosis of the temporomandibular joint.
AB  - INTRODUCTION: Restoration of normal function and jaw movement in patients with
      temporomandibular joint (TMJ) ankylosis is difficult. Various techniques have
      been defined for the treatment of the condition. PATIENTS: This study is based on
      the pre-, intra- and post-operative evaluation of 78 TMJ operations in 59
      patients who were treated for TMJ ankylosis between 1985 and 2002. METHODS: The
      patients in this study were evaluated with regard to age, gender, aetiology of
      ankylosis, ankylosis type/classification, existing facial asymmetry, maximal pre-
      and post-operative mouth opening, the arthroplasty methods (gap and
      interpositional arthroplasty) including complications and recurrence of
      ankylosis. RESULTS: Falls represented the most widespread aetiological factor
      (85%), and women constituted the group with the highest incidence of ankylosis
      (61%). Forty cases were unilateral (68%) and 19 bilateral (32%); 82% (64 joints)
      were of the bony type. Gap arthroplasty was applied in 34 of the 59 cases (58%)
      and interpositional arthroplasty in the remaining 25 (42%). Pre- and post
      operative mean mouth opening were 3.5+/-1.7 and 30.7+/-3.0mm, respectively. Re
      ankylosis was noted in 5%. CONCLUSION: In addition to radical and sufficient
      resection of the ankylosed bone, early post-operative exercises, appropriate
      physiotherapy and close follow-up of the patient play an important role in the
      prevention of post-operative adhesions and re-ankylosis.

PMID- 16423531
TI  - Ossification of the frontal sinus in juvenile minipigs following water jet
      application.
AB  - BACKGROUND: Obliteration of the frontal sinus is a generally accepted management
      for patients with severe craniofacial trauma in whom the sinus cannot be repaired
      or adequately drained. Effective obliteration requires complete removal of
      mucosa, sufficient filling of the sinus cavity as well as effective occlusion of
      the nasofrontal duct. The use of various filling materials for sinus obliteration
      has been described and include autologous fat, bone, muscle and lyophilized
      cartilage. MATERIAL AND METHODS: In order to appreciate the advantages of the
      water-jet scalpel an animal study in 10 juvenile (4 months old) and 10 adult (18
      months) minipigs was performed. In 5 juvenile and 5 adult animals the frontal
      sinus mucosa was removed using the water jet, while in the others bone curettes
      were used. No occlusion of the frontonasal duct was carried out and no filling
      material was implanted. All animals were followed-up for 40 days. After
      sacrifice, radiological, histological and computerized histomorphometrical
      examinations were carried out. RESULTS: Removal of the mucosa from the sinus was
      simplified when using the water jet. Previous studies have shown that the
      selected tissue structures were less traumatized when compared with conventional
      surgical techniques. In young animals (only) and exclusively following the use of
      a water-jet scalpel osseous occlusion of the frontal sinus was found at follow
      up. Histomorphometric findings revealed a significant increase of bone formation
      in the frontal sinus area of these animals. CONCLUSION: Based on these
      experimental results in a small series of juvenile minipigs the water-jet
      technique is a faster and less traumatic technique (less blood loss) for
      osteoplastic surgery of the frontal sinus. Further long-term studies are needed
      to evaluate the possibilities for applying this technique in post-traumatic
      craniofacial surgery in man.

PMID- 16423532
TI  - Outcome after mitral valve repair for acute and healed infective endocarditis.
AB  - OBJECTIVE: To evaluate the long-term clinical and echocardiographic outcomes
      after mitral valve surgery for acute and healed infective endocarditis. METHODS:
      Of 37 consecutive patients presenting with native mitral valve endocarditis,
      mitral valve repair (MVRep) was feasible in 34 (92%) patients. In 17 (50%)
      patients, surgery was indicated during antibiotic therapy (acute endocarditis),
      whereas 17 (50%) underwent surgery after antibiotic therapy was completed (healed
      endocarditis). Patients were evaluated for early and long-term clinical and
      echocardiographic outcome. RESULTS: In-hospital death occurred in two (6%)
      patients and two (6%) died during follow-up, with a 2-year survival of 100% in
      healed endocarditis as compared to 76% (p=0.03) in patients undergoing surgery in
      acute endocarditis. No patient with acute endocarditis needed repeat mitral valve
      surgery. Three (9%) patients underwent re-operation because of early mitral
      regurgitation (n=1) or late recurrent endocarditis (n=2). The average grade of
      mitral regurgitation was 3.8+/-0.4 (all grades 3 to 4+) before surgery and 0.6+/
      0.8 during follow-up (p<0.001). Significant reductions in left atrial (from 52+/
      8mm to 46+/-8mm, p=0.004), left ventricular end-diastolic (from 61+/-8mm to 54+/
      8mm, p=0.001), and end-systolic dimensions (from 41+/-8mm to 36+/-9 mm, p=0.02)
      were observed during follow-up, compared to preoperative dimensions. Of note,
      significant reverse remodeling was only observed in patients undergoing surgery
      in healed endocarditis. CONCLUSION: MVRep for mitral valve endocarditis is
      feasible with good clinical results, maintained valve competency with significant
      reductions in left atrial and left ventricular dimensions after surgery.

PMID- 16423533
TI  - Aorto-bronchial fistula following aortic and bronchial stenting of a thoracic
      aneurysm.
AB  - A 66-year-old man underwent repair of an abdominal aortic aneurysm and
      synchronous stenting of a thoracic aneurysm compressing his left main bronchus.
      This resulted in further bronchial compression which was also stented. An aorto
      bronchial fistula resulting in severe haemoptysis occurred a few weeks later.
      This was successfully treated with repeat endovascular stenting and left
      pneumonectomy. Open repair should be the treatment of choice for thoracic
      aneurysms with bronchial compression.

PMID- 16423534
TI  - Adjunct brachytherapy: a new concept to prevent intimal hyperplasia after
      surgical endarterectomy?
AB  - OBJECTIVE: Endarterectomy represents a therapeutical option for patients with
      advanced coronary artery disease. The mid-term results are compromised by
      restenosis due to neointima formation. The aim of this study was to evaluate a
      new treatment concept - endarterectomy with consecutive gamma-irradiation - in a
      rat model. METHODS: Male Sprague-Dawley rats underwent left carotid
      endarterectomy with removal of intima: control (n=10) or were irradiated with 15
      Gray (Gy) (n=13) or 20 Gy (n=10) postoperatively and compared with sham-operated
      rats (n=10). After 3 weeks, carotid arteries were perfusion-fixed and vessel
      compartment areas were measured. Transmission electron microscopy and
      immunohistochemical staining were used to confirm neointima formation. RESULTS:
      Three weeks after endarterectomy, neointimal hyperplasia was found in the control
      group (0.07+/-0.04 mm(2)). After irradiation, a dose-dependent reduction of
      neointima was observed (0.003 mm(2) at 15 Gy and 0.0007 mm(2) at 20 Gy,
      P<0.0001). However, immunohistochemical staining revealed that thin re
      endothelialization after irradiation was not inhibited. CONCLUSIONS: Gamma
      irradiation significantly suppressed neointimal hyperplasia in a rat model of
      surgical endarterectomy. Despite inhibition of intimal hyperplasia, re
      endothelialization after adjuvant brachytherapy was present. Adjuvant
      brachytherapy may be therefore a new concept to prevent restenosis after
      endarterectomy in patients.

PMID- 16423536
TI  - Platelet-monocyte pro-coagulant interactions in on-pump coronary surgery.
AB  - OBJECTIVE: Platelets and monocytes possess haemostatic properties, but the
      clinical effect of platelet-monocyte interactions on haemostasis following
      coronary surgery is not known. The study characterises the platelet and monocyte
      responses in cardiac surgery and its impact on haemostasis. METHODS: In 1342
      patients, changes in white blood cell counts (WBC), monocyte counts and platelet
      counts were measured. PMC formation was analysed by flow-cytometry using
      monoclonal antibodies against pan-leucocyte marker CD45, monocyte marker CD14 and
      platelet marker CD42. TF expression was determined using monoclonal antibodies
      against, CD45, CD14 and human-TF. Continuous variables were expressed as mean+/
      SD. Changes in monocyte and platelet counts over time were considered as repeated
      measures data, and analysed using Generalised Estimating Equations (GEE).
      Multivariate regression analysis was used to evaluate the effect of several
      factors on blood loss. RESULTS: A monocytosis occurs with on-pump coronary
      surgery, but is less pronounced than with off-pump surgery. No difference was
      seen in patients having redo-surgery or more complex cardiac surgery. Factors
      associated with monocytosis on multivariate analysis were higher body mass index
      (p=0.02), diabetes (p=0.035) and smoking (p=0.01). Older patients manifested a
      lower response (p<0.001). Cross-clamp fibrillation was associated with a lower
      (p=0.048) monocytic response than was cardioplegia. PMC formation dropped
      following administration of heparin, peaked at 5 min of CPB, and declined by 2h
      of CPB (p=0.04). A return towards preoperative levels was found during
      postoperative days 1-5. No significant change in monocyte TF expression occurred.
      The mean postoperative blood loss was 581.2+/-292.8 ml, and inversely related to
      increasing preoperative platelet counts (p<0.001), and to higher monocyte %
      counts (p=0.012). Patients, who were female (p<0.001), had higher body mass
      indices (p<0.001), and higher core body temperatures during surgery (p=0.013), as
      well as patients having perioperative aprotinin (p<0.001) related to less blood
      loss. CONCLUSIONS: A higher postoperative platelet count as well as monocyte%
      significantly and independently decreases postoperative blood loss following
      cardiac surgery.

PMID- 16423535
TI  - Mitral valve repair robotic versus sternotomy.
AB  - OBJECTIVE: Robotically assisted mitral valve repair were compared with sternotomy
      mitral valve repair. Prospectively we evaluated safety and efficacy in performing
      simple mitral repairs. METHODS: Between February 2004 and September 2005, 25
      patients with posterior leaflet insufficiency underwent mitral valve repair using
      the da Vinci system. They were matched retrospectively with 25 patients who
      underwent the same repair via a median sternotomy. The minimal invasive repairs
      were performed with peripheral cardiopulmonary bypass, transthoracic aortic cross
      clamp, and antegrade cardioplegia. Repair was performed with two ports and a 4-cm
      intercostals lateral incision in the right chest for access. All patients had
      posterior leaflet resection and placement of a ring annuloplasty. RESULTS: All
      patients had successful valve repairs. There were no deaths. There was one
      conversion to an extended thoracotomy in the minimal invasive group due to a
      bleeder on the left atrial appendage. Overall mean study times showed a longer
      aortic cross-clamp (range, 96.1 min vs 69.6 min) and cardiopulmonary bypass
      (range, 122.1 min vs 85.7 min) for the minimal invasive group. Length of stay was
      less for the minimal group (7 days vs 9 days). At postoperative echocardiography
      two patients in both group developed 2+ mitral regurgitations. All other patients
      had a competent mitral valve repair with no insufficiency. CONCLUSIONS: Simple
      mitral valve repair can be successfully performed with the da Vinci robotic
      system. This approach is as safe as a sternotomy and long-term follow-up is
      needed to determine the durability of the mini invasive repair.

PMID- 16423537
TI  - Functional control of regulatory T cells and cancer immunotherapy.
AB  - Regulatory T (Treg) cells induce immune tolerance by suppressing host immune
      responses against self- or non-self-antigens. Hence, they not only play critical
      roles in preventing autoimmune diseases, but also may have detrimental effects on
      vaccines directed to cancer and infectious diseases. Understanding the antigen
      specificity and functional control of Treg cells will be crucial to the
      development of effective cancer immunotherapy. This review will discuss different
      subsets of Treg cells, the factors that contribute to Treg cell generation and
      suppressive function, and the ability of signaling through Toll-like receptor 8
      to reverse the suppressive function of Treg cells. Importantly, this TLR pathway
      does not depend on interaction with dendritic cells, but operates independently
      in Treg cells, relying on TLR8 (with MyD88 as its sole receptor-proximal adaptor)
      to transduce signals generated by TLR8 ligands. Linking TLR signaling to the
      functional control of Treg cells opens intriguing opportunities to shift the
      balance between CD4(+) T-helper and Treg cells, in ways that may improve the
      outcome of cancer immunotherapy.

PMID- 16423538
TI  - Muscle specificity in tests of cervical flexor muscle performance.
AB  - The deep cervical flexor (DCF) muscles are considered to be of substantial
      clinical importance in the management of neck pain. While conventional cervical
      flexion (CF) dynamometry methods have been used frequently to assess the capacity
      of the cervical flexor muscles, it has been suggested that cranio-cervical
      flexion (CCF) methods may provide a more specific test of DCF muscle performance.
      This study compared the activation of the deep and superficial cervical flexor
      muscles between tests of isometric cranio-cervical flexion (CCF) and conventional
      cervical flexion (CF) dynamometry. Normalised root-mean-square values were
      recorded for the deep cervical flexor (DCF), sternocleidomastoid (SCM), anterior
      scalene (AS), and sternohyoid (SH) muscles during isometric CCF and CF tests at
      maximal voluntary contraction (MVC), 50% MVC, and 20% MVC in ten healthy
      volunteers. The results demonstrated significantly greater electromyography (EMG)
      amplitude for the SCM (P<.001-.002) and AS (P<.001-.001) muscles in the CF test
      conditions (MVC, 20%MVC, and 50%MVC) compared to CCF test conditions. Moreover,
      the SH muscle demonstrated significantly greater EMG amplitude during CF compared
      to CCF but only in the 50% MVC and 20% MVC conditions (P=.007 and .02
      respectively). These results demonstrate that dynamometry tests of CF result in
      greater activity of the superficial cervical flexor muscles compared to tests of
      CCF. As a result, CCF dynamometry may provide a more specific method to assess
      and retrain DCF muscle performance, compared to conventional CF in which
      superficial muscle activity may mask impaired performance of the DCF muscles.

PMID- 16423539
TI  - Reliability of electromyographic normalization methods for evaluating the hip
      musculature.
AB  - The purpose of this study was to determine the reliability of three normalization
      methods for analyzing hip abductor activation during rehabilitation exercises.
      Thirteen healthy subjects performed three open kinetic chain and three closed
      kinetic chain hip abductor exercises. Surface EMG activity for the gluteus medius
      was collected during each exercise and normalized based on a maximum voluntary
      isometric contraction (MVIC), mean dynamic (m-DYN), and peak dynamic activity (pk
      DYN). Intraclass coefficient correlations (ICCs), intersubject coefficients of
      variation (CVs), and intrasubject CVs were then calculated for each normalization
      method. MVIC ICCs exceeded 0.93 for all exercises. M-DYN and pk-DYN ICCs exceeded
      0.85 for all exercises except for the sidelying abduction exercise. Intersubject
      CVs ranged from 55% to 77% and 19% to 61% for the MVIC and dynamic methods,
      respectively. Intrasubject CVs ranged from 11% to 22% for all exercises under all
      normalization methods. The MVIC method provided the highest measurement
      reliability for determining differences in activation amplitudes between hip
      abductor exercises in healthy subjects. Future research should determine if these
      same results would apply to a symptomatic patient population.

PMID- 16423540
TI  - Selective posterior cerebral artery amobarbital test in patients with temporal
      lobe epilepsy for surgical treatment.
AB  - PURPOSE: To evaluate whether the selective posterior cerebral artery amobarbital
      test (PCAAT) can predict postoperative memory function in patients with temporal
      lobe epilepsy (TLE) for surgical treatment and its clinical safety. METHODS: The
      database included adult patients with intractable TLE undergoing presurgical
      evaluation at Taipei Veterans General Hospital between 1995 and 2002. The PCAAT
      was carried out on patients who had failed conventional intracarotid amobarbital
      test (IAT) or had IAT results that evoked a concern of postoperative memory
      function decline. A battery of learning and memory testing was performed
      immediately before and after injection of amobarbital into the peduncular segment
      of the posterior cerebral artery (PCA) on the presumed hemisphere of
      epileptogenicity. Neuropsychological assessments were followed in surgically
      treated patients. RESULTS: A total of 16 patients completed PCAAT successfully
      and underwent anterior temporal lobectomy (ATL). Four patients failed PCAAT
      angiographic procedures due to technical difficulty in one patient, transient
      signs of vasospasm in two patients, and subarachnoid hemorrhage in one patient.
      Of the 12 patients who performed well in PCAAT learning and memory testing items
      by free recall or recognition, only 1 patient demonstrated postoperative memory
      decline in follow-up neuropsychological assessments. In contrast, two of the four
      patients with a deficit in PCAAT memory testing showed postoperative memory
      decline. Regarding subjective memory function (not necessarily associated with
      objective memory decline), patients not seizure-free after ATL were more likely
      to have memory complaints (in 3 out of 6 patients) than patients with seizure
      free outcomes (in 1 out of 10 patients). CONCLUSIONS: The PCAAT memory test
      reliably predicts postoperative memory function in patients with TLE for surgical
      treatment. However, the inherent risks of PCAAT must be considered and it should
      be used judiciously.

PMID- 16423541
TI  - Sleep deprivation impairs object recognition in mice.
AB  - Many studies in animals and humans suggest that sleep facilitates learning,
      memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred
      after learning, impaired memory in humans, mice, rats, and hamsters. We
      investigated the importance of sleep and its timing in an object recognition task
      in OF1 mice subjected to 6h SD either immediately after the acquisition phase (0
      6 SD) or 6h later (7-12 SD), and in corresponding undisturbed controls. Motor
      activity was continuously recorded with infrared sensors. All groups explored two
      familiar, previously encountered objects to a similar extent, both at the end of
      the acquisition phase and 24h later during the test phase, indicating intact
      familiarity detection. During the test phase 0-6 SD mice failed to discriminate
      between the single novel and the two familiar objects. In contrast, the 7-12 SD
      group and the two control groups explored the novel object significantly longer
      than the two familiar objects. Plasma corticosterone levels determined after SD
      did not differ from time-matched undisturbed controls, but were significantly
      below the level measured after learning alone. ACTH did not differ between the
      groups. Therefore, it is unlikely that stress contributed to the memory
      impairment. We conclude that the loss of sleep and the activities the mice
      engaged in during the SD, impaired recognition memory retrieval, when they
      occurred immediately after acquisition. The delayed SD enabled memory
      consolidation during the 6h when the mice were allowed to sleep, and had no
      detrimental effect on memory. Neither SD schedule impaired object familiarity
      processing, suggesting that only specific cognitive abilities were sensitive to
      the intervention. Sleep may either actively promote memory formation, or
      alternatively, sleep may provide optimal conditions of non-interference for
      consolidation.

PMID- 16423542
TI  - Instrumental learning in hyperdopaminergic mice.
AB  - In two experiments we investigated the effects of elevated dopaminergic tone on
      instrumental learning and performance using dopamine transporter knockdown (DAT
      KD) mice. In Experiment 1, we showed that both DAT KD mice and wild-type controls
      were similarly sensitive to outcome devaluation induced by sensory specific
      satiety, indicating normal action-outcome learning in both groups. In Experiment
      2, we used a Pavlovian-to-instrumental transfer procedure to assess the
      potentiation of instrumental responding by Pavlovian conditional stimuli (CS).
      Although during the Pavlovian training phase the DAT KD mice entered the food
      magazine more frequently in the absence of the CS, when tested later both groups
      showed outcome-selective PIT. These results suggest that the elevated
      dopaminergic tone reduced the selectivity of stimulus control over conditioned
      behavior, but did not affect instrumental learning.

PMID- 16423543
TI  - Design, construction, and validation of a 1-mm triple-resonance high-temperature
      superconducting probe for NMR.
AB  - We report a 600-MHz 1-mm triple-resonance high-temperature-superconducting (HTS)
      probe for nuclear magnetic resonance spectroscopy. The probe has a real sample
      volume of about 7.5 microl, an active volume of 6.3 microl, and appears to have
      the highest mass sensitivity at any field strength. The probe is constructed with
      four sets of HTS coils that are tuned to 1H, 2H, 13C, and 15N, and there is a z
      axis gradient. The coils are cooled with a conventional Bruker CryoPlatform to
      about 20 K, and the sample chamber can be regulated above or below room
      temperature over a moderate range using a Bruker variable temperature unit. The
      absolute S/N for 0.1% ethylbenzene is approximately 1/3 that of a conventional
      5mm probe with just 1/70 of the sample volume. We demonstrate the utility of this
      probe for small molecules and proteins with 2D spectra of just 1.7 microg of
      ibuprofen and 400 microM 15N-labeled ubiquitin.

PMID- 16423544
TI  - Field-dependent nuclear relaxation of spins 1/2 induced by dipole-dipole
      couplings to quadrupole spins: LaF3 crystals as an example.
AB  - A general theory of spin-lattice nuclear relaxation of spins I=1/2 caused by
      dipole-dipole couplings to quadrupole spins S1, characterized by a non-zero
      averaged (static) quadrupole coupling, is presented. In multispin systems
      containing quadrupolar and dipolar nuclei, transitions of spins 1/2 leading to
      their relaxation are associated through dipole-dipole couplings with certain
      transitions of quadrupole spins. The averaged quadrupole coupling attributes to
      the energy level structure of the quadrupole spin and influences in this manner
      relaxation processes of the spin 1/2. Typically, quadrupole spins exhibit also a
      complex multiexponential relaxation sensed by the dipolar spin as an additional
      modulation of the mutual dipole-dipole coupling. The proposed model includes both
      effects and is valid for an arbitrary magnetic field and an arbitrary quadrupole
      spin quantum number. The theory is applied to interpret fluorine relaxation
      profiles in LaF3 ionic crystals. The obtained results are compared with
      predictions of the 'classical' Solomon relaxation theory.

PMID- 16423545
TI  - Expression of vitellogenin and cortical rod proteins during induced ovarian
      development by eyestalk ablation in the kuruma prawn, Marsupenaeus japonicus.
AB  - In penaeid shrimp species, ovarian development is characterized by the
      accumulation of a major yolk protein (vitellin) and the formation of cortical
      rods in the oocytes. The process is considered to be under the control of a
      neuroendocrine organ in the eyestalk (the X-organ sinus gland complex). In the
      present study, the synthesis of vitellogenin (VTG, precursor of vitellin) and two
      kinds of cortical rod proteins (cortical rod protein, CRP; thrombospondin, MjTSP)
      was induced by bilateral eyestalk ablation (removal of the X-organ sinus gland
      complex) in immature female kuruma prawn, Marsupenaeus japonicus, and the
      synthesis process was monitored over a 7-day period after the ablation. The
      ovarian weight and hemolymph VTG levels increased in the ablated females. The VTG
      mRNA levels in the ovary increased concomitantly with vitellin accumulation in
      the ovary after eyestalk ablation. On the other hand, the CRP and MjTSP protein
      levels in the ovary increased after eyestalk ablation, whereas the CRP and MjTSP
      mRNA levels in the ovary did not change concomitantly. The results suggest that
      the regulatory mechanism of gene expression by eyestalk hormones is different
      between VTG (transcriptional control) and CRP-MjTSP (translational control).

PMID- 16423546
TI  - Adaptation for water balance in the partial gastrointestinal tract of summer
      flounder.
AB  - Marine teleosts continually drink and absorb water across the intestine to
      prevent dehydration. Surprisingly, summer flounder that are missing most of their
      intestine, due to necrotizing enteritis, maintain osmotic homeostasis. Here, we
      tested the hypothesis that this remnant gastrointestinal tract undergoes
      compensatory adaptation for fluid uptake. Flounder (Paralicthys dentatus) with a
      partial gastrointestinal tract had an emaciated liver. Moisture content of muscle
      however was similar to healthy cohorts with an intact gastrointestinal tract,
      indicative of an undisturbed osmoregulatory status. Mass-specific rates of fluid
      uptake across all segments of the partial gastrointestinal tract were less than
      or similar to rates in corresponding segments from intact flounder. In contrast,
      weights (percent of body mass) were doubled in stomach and partial intestine of
      the remnant gastrointestinal tract. Consequently, total capacity for fluid uptake
      (microL h(-1) g body mass(-1)) was similar for both groups. The functional
      capacity of the remnant gastrointestinal tract was therefore of a magnitude
      sufficient to maintain osmoregulatory ability, further evidencing a critical role
      of the intestine in salt and water balance of marine teleosts.

PMID- 16423547
TI  - Involvement of norepinephrine in the hyperglycemic responses of the freshwater
      giant prawn, Macrobrachium rosenbergii, under cold shock.
AB  - Hyperglycemic response of freshwater giant prawn, Macrobrachium rosenbergii,
      under acute cold shock was investigated, and the involvement and stimulatory
      pathways of norepinephrine (NE) on induced-glycemia were further examined.
      Remarkable elevations in hemolymph glucose at comparable magnitude were observed
      in both intact and eyestalkless prawn under cold treatments, suggesting that
      hyperglycemic response of this species is not solely mediated through the actions
      of crustacean hyperglycemic hormone released from X-organ sinus gland complex on
      the target tissues, but NE is involved. Positive and significant correlations
      were noted between the hemolymph glucose titers and NE contents in both thoracic
      ganglia and the hemolymph, suggesting that NE plays a significant role in the
      hyperglycemic responses of this species under cold. Depressive effects of various
      adrenoceptor antagonists monitored in vivo and in vitro further suggest that the
      action of NE is primarily mediated through both alpha1- and beta1-adrenoceptors.

PMID- 16423548
TI  - Purification and kinetic properties of elisabethatriene synthase from the coral
      Pseudopterogorgia elisabethae.
AB  - The Bahamian octocoral Pseudopterogorgia elisabethae is the source of
      pseudopterosins, diterpene glycosides with potent anti-inflammatory activity. The
      first committed step in pseudopterosin biosynthesis comprises the cyclisation of
      the universal diterpene precursor geranylgeranyl diphosphate to elisabethatriene.
      This reaction is catalysed by elisabethatriene synthase, which was purified to
      homogeneity from a crude coral extract. This represents the first purification to
      apparent homogeneity of a terpene cyclase from any marine source. The reaction
      kinetics of elisabethatriene synthase was examined using a steady state approach
      with (3)H-labelled isoprenyldiphosphates varying in carbon chain length (C(10),
      C(15), C(20)). For the reaction of elisabethatriene synthase with its natural
      substrate geranylgeranyl diphosphate, values of K(m) (2.3 x 10(-6) M), V(max)
      (3.4 x 10(4) nM elisabethatriene x s(-1)) and the specificity constant
      (k(cat)/K(m)= 1.8 x 10(-10) M(-1) x s(-1)) were comparable with diterpene
      cyclases from terrestrial plants. Elisabethatriene synthase also catalysed the
      conversion of C(15) and C(10) isoprenyldiphosphate analogues to monoterpene and
      sesquiterpene olefins, respectively. Kinetic parameters indicated that substrate
      specificity and K(m) of elisabethatriene synthase decreased with decreasing
      isoprenoid carbon chain length. Furthermore, GC-MS analysis showed increased
      product diversity with decreasing isoprenoid carbon chain length.

PMID- 16423549
TI  - Can the DCoHalpha isozyme compensate in patients with 4a-hydroxy
      tetrahydrobiopterin dehydratase/DCoH deficiency?
AB  - 4a-Hydroxy-tetrahydrobiopterin dehydratase/DCoH is a bifunctional protein. In the
      cytoplasm it is an enzyme required for the regeneration of tetrahydrobiopterin,
      an essential cofactor for phenylalanine hydroxylase. In the nucleus it functions
      as a transcriptional coactivator by forming a 2:2 heterotetramer with the hepatic
      nuclear factor HNF1alpha (HNF1). Patients with a deficiency of dehydratase
      activity have elevated levels of phenylalanine, and accumulate 7-pterins due to
      degradation of its substrate 4a-hydroxy-tetrahydrobiopterin. Curiously, the
      hyperphenylalaninemia is transient, and no defects in the transcriptional
      coactivator function have been reported. Recently, a human isozyme,
      dehydratase/DCoHalpha, has been detected which shares 60% identity with
      dehydratase/DCoH. This investigation was undertaken to ascertain if
      dehydratase/DCoHalpha has the pre-requisite properties to compensate in
      individuals lacking an active form of DCoH. DCoHalpha demonstrated the ability to
      quantitatively alter HNF1-dependent DNA-binding in vitro whereas DCoH was
      ineffective in vitro. This characteristic, due to the presence of dimeric
      DCoHalpha, demonstrates that DCoHalpha does not require any additional mammalian
      regulation process to alter DNA binding and therefore, may be more effective than
      DCoH at low concentrations. The dehydratase activity of each isoform was measured
      by a direct spectrophotometric assay. Km and Vmax for DCoHalpha were both 2-3
      times higher than for DCoH, thus leaving the catalytic efficiency (Vmax/Km) the
      same for both enzymes. In conclusion, the properties of dehydratase/DCoHalpha are
      consistent with the hypothesis that the activity of this isozyme could account
      for the relatively mild symptoms reported for patients with a defect in
      dehydratase/DCoH.

PMID- 16423550
TI  - Mutational spectrum of cystic fibrosis patients from Cordoba province and its
      zone of influence: implications of molecular diagnosis in Argentina.
AB  - Cystic Fibrosis (CF) is an autosomal recessive disorder affecting 1/2000-4000
      newborns in Caucasian populations. This lethal disease mainly affects respiratory
      and digestive organs as well as fertility in man. So far, the CF prevalence and
      mutational spectrum have showed specificity among populations and regions, making
      it necessary to establish them in each one. In this study, we present the
      spectrum and frequency of CFTR gene mutations in CF patients from Cordoba (a
      province with 3.1 millions inhabitants in the middle of Argentina) and its zone
      of influence, to offer an accurate genetic testing. The study includes 78
      families in which 98 patients fulfilled clinical criteria to CF diagnosis. The
      strategy for the molecular diagnosis comprised analysis of 21 common mutations,
      microsatellite haplotypes and the complete CFTR gene analysis using scanning
      techniques followed by sequencing of the abnormal migration patterns. Our first
      step led us to the identification of 10 mutations that represented 76% of
      alleles. Another four mutations (p.R1066C, c.1811 + 1.6 kbA > G, c.711 + 1G > T,
      and p.G85E) were found based on the microsatellite haplotype-mutation
      association. Finally, 14 mutations were characterized after the CFTR gene
      scanning, three of them are not previously described (p.G27R, c.622-2A > G, and
      p.W277R). In summary, we have identified 27 mutations accounting for 94.23% of CF
      alleles. This characteristic mutational spectrum highlights the 14 most frequent
      mutations (>1%) in the Cordoba region.

PMID- 16423551
TI  - Ultrasonic enhancement of the supercritical extraction from ginger.
AB  - This work examines the concurrent use of power ultrasound during the extraction
      of pungent compounds from a typical herb (ginger) with supercritical CO(2). A
      power ultrasonic transducer with an operating frequency of 20 kHz is connected to
      an extraction vessel and the extraction of gingerols from freeze-dried ginger
      particles (4-8 mm) is monitored. In the presence of ultrasound, we find that both
      the extraction rate and the yield increase. The higher extraction rate is
      attributed to disruption of the cell structures and an increase in the
      accessibility of the solvent to the internal particle structure, which enhances
      the intra-particle diffusivity. While cavitation would readily account for such
      enhancement in ambient processes, the absence of phase boundaries should exclude
      such phenomena above the critical point. Possible alternate mechanisms for the
      cell structure damage are discussed.

PMID- 16423553
TI  - Pancreatic acinar cell: its role in acute pancreatitis.
AB  - The pancreatic acinar cell is the functional unit of the exocrine pancreas. It
      synthesizes, stores, and secretes digestive enzymes. Under normal physiological
      conditions, digestive enzymes are activated only once they have reached the
      duodenum. Premature activation of these enzymes within pancreatic acinar cells
      leads to the onset of acute pancreatitis; it is the major clinical disorder
      associated with pancreatic acinar cells. Although there have been major advances
      in our understanding of the pathogenesis of this disease in recent years,
      available treatment options are still limited to traditional nonspecific and
      palliative interventions. Novel therapeutic strategies have been suggested based
      on ongoing research in the physiology and pathophysiology of the disease; these
      include the administration of systemic antibiotics, antioxidants, cytokine
      antagonists, and more recently, inhibition of the renin-angiotensin system.
      Notwithstanding this promising development, most of these potential therapies are
      still in an experimental stage or clinical trial. Further investigation is needed
      to prove the efficacy of these novel treatment modalities.

PMID- 16423552
TI  - Jun signalling in the epidermis: From developmental defects to psoriasis and skin
      tumors.
AB  - The Jun proteins Jun, JunB and JunD are core members of activator protein-1 (AP
      1), a dimeric transcription factor complex consisting of homo- and heterodimers
      of the Jun, Fos, activating transcription factor (ATF) and musculoaponeurotic
      fibrosarcoma (Maf) families. Growth factors, hormones and a variety of
      environmental stresses activate mitogen activated protein kinase (MAPK) cascades
      that enhance Jun/AP-1 activity, e.g. through phosphorylation thereby regulating
      cell proliferation, differentiation, transformation and/or apoptosis. Embryonic
      lethality of various AP-1 knock-outs, e.g. for Jun, JunB, Fra-1 and Fra-2 largely
      prevented functional studies in vivo. Therefore, conditional knock-out
      strategies, in particular for the epidermis, have become an important model to
      study the regulation and function of AP-1 subunits in physiological and
      pathological processes in vivo. Jun is regarded as a positive regulator of
      keratinocyte proliferation/differentiation during development and in skin cancer
      through its direct transcriptional effect on epidermal growth factor receptor
      (EGFR) expression. In contrast, JunB can antagonize proliferation of
      keratinocytes and hematopoietic stem cells. Furthermore, it has been demonstrated
      in patient's samples and an inducible mouse model that down-regulation of JunB/AP
      1 in keratinocytes is one initiating event in the aetiology of psoriasis which is
      characterized by increased cell proliferation and deregulated cytokine
      expression.

PMID- 16423554
TI  - Outcome of preoperative concurrent chemoradiotherapy and surgery for resectable
      lingual squamous cell carcinoma greater than 3 cm: the possibility of less
      extensive surgery.
AB  - We present the outcome of treatment with preoperative concurrent
      chemoradiotherapy and surgery for resectable lingual squamous cell carcinoma more
      than 3 cm in its greatest dimension. Twenty patients were enrolled in this study
      between June 2001 and August 2004. Concurrent chemoradiotherapy included
      intraarterial pirarubicin (THP) (5 mg/day), intravenous continuous 5-FU, and
      radiation, usually followed by surgery. Complete response rate was 100%. Notably,
      8 of 12 patients who underwent surgery exhibited pathologically complete
      response, though three patients developed recurrence or distant metastasis. The
      main adverse effects were mucositis (13/20) and leucopenia (9/20), both of which
      were acceptable. Although long-term results should be considered, our treatment
      method appears very useful for lingual squamous cell carcinoma greater than 3 cm,
      with a remarkably high rate of pathological local control and acceptable adverse
      events.

PMID- 16423557
TI  - Detection of 4-oxo-2-hexenal, a novel mutagenic product of lipid peroxidation, in
      human diet and cooking vapor.
AB  - Since the diet plays an important role in the development of human cancer, it is
      important to identify mutagens in foods. We have detected a novel mutagenic
      product, 4-oxo-2-hexenal (4-OHE), in a model lipid peroxidation reaction mixture
      [H. Kasai, M. Maekawa, K. Kawai, K. Hachisuka, Y. Takahashi, H. Nakamura, R.
      Sawa, S. Matsui, T. Matsuda, 4-Oxo-2-hexenal, a mutagen formed by omega-3 fat
      peroxidation, causes DNA adduct formation in mouse organs, Ind. Health 43 (2005)
      699-701]. In the present study, the contents of 4-OHE in various food samples
      were determined by a GC/MS method. Commercial perilla oil (derived from the seed
      of Perilla frutescens var. frutescens), which is rich in linolenic acid
      triglyceride (TG), the edible part of broiled fish, and various fried foods
      contained 4-OHE in the range of 1-70 microg/g. Furthermore, from the ethyl
      acetate trap (extracts) of the smoke released during the broiling of fish, 4-OHE
      was also detected by GC/MS. These results provide a warning to humans, who may be
      exposed to this mutagen. The 4-OHE may be produced from omega-3 polyunsaturated
      fats, such as alpha-linolenic acid-, docosahexaenoic acid (DHA)- and
      eicosapentaenoic acid (EPA)-TG, which are more easily oxidized than omega-6 fats,
      such as linoleic acid-TG.

PMID- 16423558
TI  - Development of nonalcoholic steatohepatitis model through combination of high-fat
      diet and tetracycline with morbid obesity in mice.
AB  - Nonalcoholic steatohepatitis (NASH) is a chronic liver disease closely associated
      with obesity, type 2 diabetes and hyperlipidemia. For further understanding of
      NASH, development and characterization of appropriate animal models with
      metabolic abnormalities is important. Based on the "two hit theory", we tried to
      develop a new murine model of NASH with metabolic abnormalities. For the first
      hit to achieve metabolic abnormalities, a high-fat diet (HFD: 60 cal% fat) was
      fed to C57BL/6 mice for 10 weeks. For the second hit, 30mg/kg tetracycline was
      injected intraperitoneally once daily for 10 days. The HFD-fed mice treated with
      tetracycline showed robust increases in triglyceride content and expression
      levels of proinflammatory cytokine mRNAs in the liver. In addition, plasma ALT
      levels were significantly elevated by this combinational treatment. Furthermore,
      histological examination demonstrated that combinational treatment induced
      multifocal inflammatory cellular infiltration in the livers of all mice, and thus
      caused mild steatohepatitis. The HFD-tetracycline model could be useful for
      further understanding NASH.

PMID- 16423555
TI  - DNA damage evaluated by gammaH2AX foci formation by a selective group of
      chemical/physical stressors.
AB  - It has been reported that the phosphorylated form of histone variant H2AX
      (gammaH2AX) plays an important role in the recruitment of DNA repair and
      checkpoint proteins to sites of DNA damage, particularly at double strand breaks
      (DSBs). Using gammaH2AX foci formation as an indicator for DNA damage, several
      chemicals/stress factors were chosen to assess their ability to induce gammaH2AX
      foci in a 24h time frame in a human amnion FL cell line. Two direct-acting
      genotoxins, methyl methanesulfonate (MMS) and N-ethyl-N-nitrosourea (ENU), can
      induce gammaH2AX foci formation in a time- and dose-dependent manner. Similarly,
      an indirect-acting genotoxin, benzo[a]pyrene (BP), also induced the formation of
      gammaH2AX foci in a time- and dose-dependent manner. Another indirect genotoxin,
      2-acetyl-aminofluorene (AAF), did not induce gammaH2AX foci formation in FL
      cells; however, AAF can induce gammaH2AX foci formation in Chinese hamster CHL
      cells. Neutral comet assays also revealed the induction of DNA strand breaks by
      these agents. In contrast, epigenetic carcinogens azathioprine and cyclosporine
      A, as well as non-carcinogen dimethyl sulfoxide, did not induce gammaH2AX foci
      formation in FL cells. In addition, heat shock and hypertonic saline did not
      induce gammaH2AX foci. Cell survival analyses indicated that the induction of
      gammaH2AX is not correlated with the cytotoxic effects of these agents/factors.
      Taken together, these results suggest that gammaH2AX foci formation could be used
      for evaluating DNA damage; however, the different cell types used may play an
      important role in determining gammaH2AX foci formation induced by a specific
      agent.

PMID- 16423559
TI  - Fasting plasma ghrelin levels reflect malnutrition state in patients with liver
      cirrhosis.
AB  - BACKGROUND AND AIM: Ghrelin plays an important role in controlling the feeding
      and nutritional states by signaling hypothalamic centers. However, the role of
      ghrelin in cirrhotic patients in the malnutrition state remains unclear. SUBJECTS
      AND METHODS: Thirty-four patients with liver cirrhosis (LC) and 10 healthy
      controls (normal controls, NC) were enrolled in this study. Fasting plasma
      ghrelin levels (desacyl form) were measured using a newly developed ELISA and the
      relationship among biochemical parameters including plasma leptin, body
      composition and energy metabolism were evaluated using an indirect calorimeter.
      RESULTS: Plasma ghrelin levels were slightly but not significantly elevated in
      patients with LC when compared with NC. Plasma ghrelin levels showed a negative
      correlation (r=-0.432, p<0.01) with plasma leptin levels and positive
      correlations with blood urea nitrogen (BUN), creatinine, white blood cell count
      and C-reactive protein. No correlation with the severity of liver damage based on
      the classification of Child-Pugh was noted. Plasma ghrelin levels were
      significantly correlated with body mass index (BMI), arm muscular circumference
      (AMC), triceps skinfold thickness (TSF) (BMI, r=-0.389, p<0.05; AMC, r=-0.416,
      p<0.05; TSF, r=-0.459, p<0.01, respectively) and the substrate oxidation rates of
      glucose (%CHO), fat (%FAT) and non-protein respiratory quotients (npRQ) (%CHO, r=
      0.391, p<0.05; %FAT, r=0.438, p<0.01; npRQ, r=-0.411, p<0.05, respectively). Four
      factors (npRQ, TSF, total bilirubin, BUN) associated with plasma ghrelin levels
      were identified by multiple regression analysis. CONCLUSIONS: These data suggest
      that fasting plasma ghrelin levels may be a useful indicator reflecting
      malnutrition in patients with LC, although renal failure and inflammatory status
      are also closely associated with plasma ghrelin levels.

PMID- 16423560
TI  - Altered CD45 expression and disease.
AB  - CD45, the leucocyte common antigen, is a haemopoietic cell-specific tyrosine
      phosphatase. Many isoforms are generated by alternative splicing, but their
      function remains obscure. The extracellular domain of CD45 is highly polymorphic
      in all vertebrates. Importantly, human polymorphic variants that alter CD45
      isoform expression are associated with autoimmune and infectious diseases,
      establishing CD45 as an important immunomodulator with a significant influence on
      disease burden. Here, we discuss the new opportunities provided by the human
      variants for investigating and understanding how CD45 regulates antigen receptor
      signalling, cytokine responses and apoptosis.

PMID- 16423561
TI  - CNS gene therapy applications of the Semliki Forest virus 1 vector are limited by
      neurotoxicity.
AB  - The Semliki Forest virus (SFV) 1 vector system is highly efficient at gene
      transduction in a broad range of host cells, including neurons. To determine the
      potential of SFV1-based vectors to mediate gene expression in substantia nigra
      neurons, we inoculated d1EGFP-expressing SFV virus-like particles stereotaxically
      into the mouse brain. This system selectively and extensively mediated gene
      expression in dopaminergic neurons of the substantia nigra. Continual reporter
      gene expression was evident in neuronal cell bodies for up to 3 weeks
      postinoculation and d1EGFP-positive neuronal processes were apparent for 12
      weeks. There was no evidence of an apoptotic response to infection, but with time
      cell degeneration and an axonopathy, indicative of neuronal loss, were
      increasingly apparent. This system has potential for experimental studies
      requiring efficient transient gene transduction of mouse CNS neurons. The current
      SFV1 vector system is, however, limited in its potential for CNS gene therapy by
      neurotoxicity.

PMID- 16423562
TI  - Temperature increase results in oxidative stress in goldfish tissues. 1. Indices
      of oxidative stress.
AB  - Levels of lipid peroxides (LOOH), thiobarbituric-acid reactive substances
      (TBARS), protein carbonyls and low- and high-molecular weight thiols were
      measured in brain, liver, kidney, and white muscle of goldfish, Carassius auratus
      L., over 1-12 h of high temperature (35 degrees C) exposure followed by 4 or 24 h
      of lower (21 degrees C) temperature recovery. LOOH and TBARS contents increased
      during heat shock exposure with a maximal rise of 20-fold for liver TBARS, but
      both mainly reversed at recovery. Protein carbonyl content was unaffected by heat
      shock but rose in brain, liver, and kidney during recovery. Low-molecular weight
      thiol concentrations unexpectedly increased up to approximately 4-fold in brain,
      kidney and muscle under heat shock and remained high during recovery. Protein
      thiol contents also rose in liver and muscle during high temperature exposure by
      2- and 3-fold, respectively, and decreased to control values or below in all
      tissues at late recovery. Low- and high-molecular weight thiol levels inversely
      correlated in liver (R2=0.87) suggesting that the former was used to reduce the
      latter over the experiment. It is concluded that the redox balance in goldfish
      tissues is strictly maintained probably contributing to the high tolerance of
      this species to heat shock.

PMID- 16423563
TI  - Invertebrate intracellular fatty acid binding proteins.
AB  - Fatty acid binding proteins are multigenic cytosolic proteins largely distributed
      along the zoological scale. Their overall identity at primary and tertiary
      structure is conserved. They are involved in the uptake and transport of
      hydrophobic ligands to different cellular fates. The precise functions of each
      FABP type remain imperfectly understood, since sub-specialization of functions is
      suggested. Evolutionary studies have distinguished major subfamilies that could
      have been derived from a common ancestor close to vertebrate/invertebrate split.
      Since the isolation of the first invertebrate FABP from Schistocerca gregaria in
      1990, the number of FABPs isolated from invertebrates has been increasing.
      Differences at the sequence level are appreciable and relationships with
      vertebrate FABPs are not clear, and lesser among invertebrate proteins,
      introducing some uncertainty to infer functional relatedness and phylogenetic
      relationships. The objective of this review is to summarize the information
      available on invertebrate FABPs to elucidate their mutual relationships, the
      relationship with their vertebrate counterparts and putative functions.
      Structure, gene structure, putative functions, expression studies and
      phylogenetic relationships with vertebrate counterparts are analyzed. Previous
      suggestions of the ancestral position concerning the heart-type of FABPs are
      reinforced by evidence from invertebrate models.

PMID- 16423564
TI  - Nitric oxide-induced nuclear translocation of the metal responsive transcription
      factor, MTF-1 is mediated by zinc release from metallothionein.
AB  - We previously showed that the major Zn-binding protein, metallothionein (MT) is a
      critical target for nitric oxide (NO) with resultant increases in labile Zn. We
      now show that NO donors also affected the activity of the metal responsive
      transcription factor MTF-1 that translocates from the cytosol to the nucleus in
      response to physiologically relevant increases in intracellular Zn and
      transactivates MT gene expression. Exposing mouse lung endothelial cells (MLEC)
      to ZnCl(2) or the NO donor, S-Nitroso-N-acetylpenicillamine (SNAP, 200 microM),
      caused nuclear translocation of a reporter molecule consisting of enhanced green
      fluorescent protein (EGFP) fused to MTF-1 (pEGFP-MTF-1). In separate experiments,
      NO donors induced increases in MT protein levels (Western blot). In contrast, NO
      did not cause nuclear translocation of EGFP-MTF-1 in MLEC from MT knockouts,
      demonstrating a central role for MT in mediating this response. These data
      suggest that S-nitrosation of Zn-thiolate clusters in MT and subsequent
      alterations in Zn homeostasis are participants in intracellular NO signaling
      pathways affecting gene expression.

PMID- 16423565
TI  - Characterization of big bang, a novel gene encoding for PDZ domain-containing
      proteins that are dynamically expressed throughout Drosophila development.
AB  - PDZ (PSD-95, Discs-large, ZO-1) domain proteins often function as scaffolding
      proteins and have been shown to play important roles in diverse cellular
      processes such as the establishment and maintenance of cell polarity, and signal
      transduction. Here, we report the identification and cloning of a novel
      Drosophila melanogaster gene that is predicted to produce several different PDZ
      domain-containing proteins through alternative promoter usage and alternative
      splicing. This gene, that we have named big bang (bbg), was first identified as
      C96-GAL4, a GAL4 enhancer trap line that was generated in our lab. To further
      characterize bbg, its expression pattern was examined in ovaries, embryos, and
      late third instar larvae using UAS reporter gene constructs, in situ
      hybridization, or immunocytochemistry. In addition, the expression of
      alternatively spliced transcripts was examined in more detail using in situ
      hybridization. We find that during embryogenesis bbg is predominantly expressed
      in the developing gut, but it is also expressed in external sensory organs found
      in the epidermis. In the late third instar larva, bbg is expressed along the
      presumptive wing margin in the wing disc, broadly in the eye disc, and in other
      imaginal discs as well as in the brain. The expression patterns observed are
      dynamic and specific during development, suggesting that like other genes that
      encode for several different PDZ domain protein isoforms, bbg likely plays
      important roles in multiple developmental processes.

PMID- 16423566
TI  - Immobilization of tyrosinase on poly(indole-5-carboxylic acid) evidenced by
      electrochemical and spectroscopic methods.
AB  - A conducting, polymeric film of poly(indole-5 carboxylic acid) has been prepared
      by electrochemical polymerization for covalent immobilization of an enzyme
      belonging to the family of phenoloxidases-tyrosinase. The polymer was
      characterized by cyclic voltammetry, UV-VIS and Raman spectroscopy in a buffer
      solution. As the polymer contains pendant carboxylic groups one-step carbodiimide
      method was used to immobilize tyrosinase on the polymer matrix. Immobilization of
      tyrosinase was confirmed by surface enhanced resonance Raman scattering spectra
      (SERRS) and by cyclic voltammetry as well. Tyrosinase was shown to retain its
      biological activity when being immobilized on the polymer surface. As proved by
      the electrochemical and spectroelectrochemical (UV-VIS) experiments, tyrosinase
      covalently bonded to the polymer matrix effectively catalyzes oxidation of
      catechol. The reduction current of o-quinones was measured as a function of
      catechol concentration. The linear dependence was found to be 15 microM of
      catechol with sensitivity of 250 mA/M cm2.

PMID- 16423567
TI  - Influence of diaphragm and rib cage muscle fatigue on breathing during endurance
      exercise.
AB  - Inspiratory muscle fatigue (IMF) can develop during exhaustive exercise and cause
      tachypnea or rapid shallow breathing. We assessed the effects of rib cage muscle
      (RCM-F) and diaphragm fatigue (DIA-F) on breathing pattern and respiratory
      mechanics during high-intensity endurance exercise. Twelve healthy subjects
      performed a constant-load (85% maximal power) cycling test to exhaustion with
      prior IMF and a cycling test of similar intensity and duration without prior IMF
      (control). IMF was induced by resistive breathing and assessed by oesophageal and
      gastric twitch pressure measurements during cervical magnetic stimulation. Both
      RCM-F and DIA-F increased RCM and abdominal muscle force production during
      exercise compared to control. With RCM-F, tidal volume decreased while it
      increased with DIA-F. RCM-F was associated with a smaller increase in end
      expiratory oesophageal pressure (i.e. decrease in lung volume) than DIA-F. These
      results suggest that RCM-F and not DIA-F is associated with rapid shallow
      breathing and that lowering the operating lung volume with DIA-F may help to
      preserve diaphragmatic function.

PMID- 16423568
TI  - Nonsurgical treatment of abdominal or pelvic abscess in consecutive patients with
      Crohn's disease.
AB  - BACKGROUND: There is little agreement about the efficacy of nonsurgical treatment
      for abscess associated with Crohn's disease. Furthermore, there is no study on
      characteristics of abscess or patient that nonsurgical treatment could be worth
      trying as initial treatment. AIMS: To evaluate the outcome of nonsurgical
      treatment in Crohn's disease-related abscess and identify factor leading to
      failure of nonsurgical treatment of this complication. PATIENTS: Twenty-four
      patients, who consecutively admitted for Crohn's disease-related abscess to our
      institution during a 7-year period, underwent nonsurgical treatment as initial
      therapy. METHODS: Outcome data such as recurrence and intractability, and
      clinical features were retrospectively analysed. Univariate analysis with patient
      related factors and abscess-related factors was performed for risk factor
      identification. RESULTS: Median follow-up period was 47.5 months. Of the eligible
      patients, 19 patients were treated medically and 5 patients underwent
      percutaneous catheter drainage with medical treatment. Overall success rate of
      nonsurgical treatment in our centre was 66.7%. The cumulative recurrence rate at
      7 months was 12.5%. All recurrences occurred within 7 months from complete
      resolution on follow-up imaging. Univariate analysis showed that the significant
      factors which lead to failure of nonsurgical treatment were presence of
      associated fistula and concurrent steroid use (P=0.019 and P=0.019,
      respectively). CONCLUSION: Nonsurgical treatment can be considered as initial
      treatment modality for the Crohn's disease-related abscess without concurrent
      steroid therapy or relevant fistula.

PMID- 16423569
TI  - Longer preservation of cardiac performance by sheet-shaped myoblast implantation
      in dilated cardiomyopathic hamsters.
AB  - OBJECTIVES: Cell therapy is a promising strategy for ischemic cardiomyopathy.
      However, the direct injection method has limitations for generalized cell
      delivery, especially in dilated cardiomyopathy (DCM). We hypothesized that a
      sheet-shaped myoblast graft would be superior to direct injection for improving
      cardiac performance in DCM. METHODS: Male 27-week-old BIO TO-2 (DCM) hamsters
      that showed moderate cardiac remodeling were used as recipients. Myoblasts
      isolated from BIO F1B hamsters were cultured on dishes coated with poly(N
      isopropylacrylamide), a temperature-responsive polymer, and spontaneously
      detached as a sheet-shaped graft at 20 degrees C without enzymatic treatment.
      Three different therapies were conducted: (1) sheet-shaped myoblast graft
      implantation (S group, n=29); (2) myoblast injection (M group, n=28); and (3)
      sham operation (C group, n=28). In the S group, two sheet-shaped myoblast grafts
      were implanted on the left ventricle (LV) wall, and in the M group, myoblasts
      were injected into the right ventricle (RV) and LV walls. RESULTS: After the
      sheet-shaped myoblast grafts were implanted, echocardiography demonstrated that
      the dilated LV dimension was significantly reduced, whereas the hearts in other
      groups showed a progression of LV dilation. The fractional shortening in the M
      and C groups decreased significantly while that in the S group was maintained at
      the preoperative level for 3 months after the operation. Histological examination
      demonstrated that in the S group, the LV wall thickness was increased, with
      viable myoblasts, and myocardial fibrosis was decreased compared with the other
      groups. Immunohistochemical staining demonstrated alpha-sarcoglycan and beta
      sarcoglycan expression on the basement membrane of the cardiomyocytes in the S
      group but not in the other groups. The life expectancy was significantly
      prolonged in the S group. CONCLUSION: Sheet-shaped myoblast graft implantation
      improved cardiac performance and prolonged life expectancy, associated with a
      reduction in myocardial fibrosis and re-organization of the cytoskeletal proteins
      in DCM hamsters. Thus, sheet-shaped autologous myoblast graft implantation may
      induce restoration of the heart in DCM.

PMID- 16423572
TI  - Experimental second passage of chronic wasting disease (CWD(mule deer)) agent to
      cattle.
AB  - To compare clinicopathological findings in first and second passage chronic
      wasting disease (CWD(mule deer)) in cattle, six calves were inoculated
      intracerebrally with brain tissue derived from a first-passage CWD-affected calf
      in an earlier experiment. Two uninoculated calves served as controls. The
      inoculated animals began to lose both appetite and weight 10-12 months later, and
      five subsequently developed clinical signs of central nervous system (CNS)
      abnormality. By 16.5 months, all cattle had been subjected to euthanasia because
      of poor prognosis. None of the animals showed microscopical lesions of spongiform
      encephalopathy (SE) but PrP(res) was detected in their CNS tissues by
      immunohistochemistry (IHC) and rapid Western blot (WB) techniques. Thus,
      intracerebrally inoculated cattle not only amplified CWD PrP(res) from mule deer
      but also developed clinical CNS signs in the absence of SE lesions. This
      situation has also been shown to occur in cattle inoculated with the scrapie
      agent. The study confirmed that the diagnostic techniques currently used for
      diagnosis of bovine spongiform encephalopathy (BSE) in the US would detect CWD in
      cattle, should it occur naturally. Furthermore, it raised the possibility of
      distinguishing CWD from BSE in cattle, due to the absence of neuropathological
      lesions and to a distinctive multifocal distribution of PrP(res), as demonstrated
      by IHC which, in this study, appeared to be more sensitive than the WB technique.

PMID- 16423571
TI  - Cytokine and Toll-like receptor mRNAs in the nasal-associated lymphoid tissues of
      cattle during foot-and-mouth disease virus infection.
AB  - The pharyngeal region is known to play an important role in foot-and-mouth
      disease virus (FMDV) infection in relation to acute disease and viral
      persistence. In this study, the local mucosal immune response in nasal-associated
      lymphoid tissue (NALT) of cattle infected with FMDV (strain O UKG 34/2001) was
      examined. Quantitative "real-time" RT-PCR assays were used to measure mRNA
      expression of cytokines (IFN-alpha, beta and gamma, IL-2, IL-1alpha and TNF
      alpha) and Toll-like receptors (TLR)-3 and -4. NALTs from dorsal soft palate were
      collected from cattle at 7 days post-infection (dpi) and from carriers and non
      carriers at 64 dpi. Expression of IFN-alpha mRNA was significantly greater in
      NALT during acute disease than in uninfected animals. Increased expression of IFN
      gamma and IL-1alpha mRNA was also observed but was much lower than IFN-alpha
      expression. There was a slight increase in mRNA expression of TNF-alpha and IL-2.
      During persistence, TNF-alpha mRNA expression in carrier cattle was much higher
      than in non-carrier cattle. Expression of TLR-4 in NALT during the acute stage of
      infection was greater than in uninfected animals. Carrier and non-carrier cattle
      did not differ in respect of expression of TLR-3 and -4 mRNA in NALT.

PMID- 16423573
TI  - Proliferative activity, apoptosis and expression of oestrogen receptor and Bcl-2
      oncoprotein in canine mammary gland tumours.
AB  - Samples of 39 canine mammary gland tumours (MGTs) were examined
      immunohistochemically for oestrogen receptor (ER-alpha), Bcl-2 protein and Ki67
      antigen, and by TUNEL assay for apoptosis. ER-alpha was expressed by 80% (31/39)
      of the tumours, including all of the 15 benign tumours and 67% (16/42) of the
      malignant tumours. ER-alpha expression was greater in the benign than in the
      malignant tumours (P<0.01). Bcl-2 protein was detected in 62% (24/39) of the
      MGTs, of which 67% (10/15) were benign and 58% (14/24) malignant. No significant
      difference in Bcl-2 expression between benign and malignant tumours was detected.
      The Ki67 and TUNEL indices were greater in malignant than in benign tumours
      (P<0.01). Correlation analysis suggested that ER-alpha and Bcl-2 expression were
      related, but this observation lacked statistical significance. The levels of cell
      proliferation and apoptosis did not appear to be significantly correlated with
      the expression of Bcl-2. A positive relationship was apparent between cell
      proliferation and apoptosis, whilst a negative correlation between ER-alpha and
      cell proliferation was demonstrated. In conclusion, the suggestion of a positive
      correlation between ER-alpha and Bcl-2 in canine MGTs indicates that ER may be
      the regulator of Bcl-2 protein, as in human breast cancer. In contrast to cell
      proliferation and apoptosis, ER-alpha and Bcl-2 expression were greater in benign
      MGTs than in their malignant counterparts.

PMID- 16423574
TI  - Histopathological and immunohistochemical investigations of hepatic lesions
      associated with congenital portosystemic shunt in dogs.
AB  - Canine livers with congenital portosystemic shunt were investigated
      histopathologically and immunohistochemically before and 8-272 days after partial
      ligation of the shunt. Lesions included hypoplasia of portal veins, arteriolar
      and ductular proliferation, lymphangiectasis, mild to moderate fibrosis, fatty
      cysts, and mostly mild hepatocellular damage with frequent atrophy and steatosis,
      regardless of the location of the shunting vessel. Perisinusoidal hepatic
      stellate cells (HSCs) in normal canine liver expressed alpha-smooth muscle actin
      (alpha-SMA), but no desmin. In altered livers, however, raised expression of
      alpha-SMA was detected, together with expression of desmin, in varying numbers of
      HSCs. This was interpreted as a sign of cellular proliferation and transformation
      to myofibroblast-like cells. Additionally, there was an obvious perisinusoidal
      increase of several extracellular matrix components. Postoperative biopsy samples
      showed basically the same lesions as those of pre-operative samples, except that
      signs of resolution of hepatic changes were apparent.

PMID- 16423575
TI  - Immunohistochemical study of STAT3 expression in feline injection-site
      fibrosarcomas.
AB  - STAT3 (signal transducer and activator of transcription 3) is a cytoplasmic
      transcription factor that plays a role in the G1 to S phase cell-cycle transition
      and is induced by cytokines and growth factors. In the present study, the
      relation between histological grade and anti-STAT3 immunoreactivity was evaluated
      in 39 feline injection-site sarcomas treated surgically, 24 of the cats having
      received preoperative treatment with doxorubicin. Anti-STAT3 immunoreactivity was
      significantly lower in cases receiving preoperative doxorubicin, specifically
      with regard to nuclear localization. Moreover, STAT3 expression (intranuclear)
      was significantly correlated with mitotic activity in the animals that did not
      receive doxorubicin (P=0.019), and with differentiation score (P=0.009). STAT3
      expression was correlated with the histological grade in both doxorubicin-treated
      and -untreated cats; in the treated cats, however, this correlation applied only
      to cytoplasmic STAT3 (P=0.018). Doxorubicin treatment induced a significant
      decrease in STAT3 expression (nuclear, P<0.0001; cytoplasmic, P=0.033) as
      compared with cases treated by surgery alone. These findings support existing
      evidence from human and experimental pathology on the potential role of STAT3 in
      oncogenesis and tumour progression.

PMID- 16423576
TI  - Brain lesions in pigs dually infected with porcine reproductive and respiratory
      syndrome virus and pseudorabies virus.
AB  - Four pigs were inoculated with an aerosol containing porcine reproductive and
      respiratory syndrome virus (PRRSV) followed 14 days later by inoculation with
      pseudorabies virus (PRV). The four dually infected pigs showed severe clinical
      signs, and one died on day 6 after infection with PRV. As demonstrated
      previously, the clinical disease was much more severe than that produced by
      either virus alone. All four dually infected pigs developed severe non
      suppurative encephalitis, two had tonsillitis, two had necrotizing bronchiolitis,
      and one had lymphadenitis. The distribution of lesions corresponded closely with
      the detection of intranuclear inclusion bodies and PRV antigen. High numbers of
      TUNEL-positive cells detected in the thymus were associated with thymic atrophy.

PMID- 16423587
TI  - Insulin sensitivity and secretion: swaying the pendulum.

PMID- 16423588
TI  - The role of genetic susceptibility for maternal alcohol metabolism in determining
      pregnancy outcome.

PMID- 16423589
TI  - Lessons from Kawasaki disease: all brands of IVIG are not equal.

PMID- 16423590
TI  - The zinc protoporphyrin/heme ratio in premature infants: has it found its place?

PMID- 16423591
TI  - Office-based objective measures in childhood asthma.

PMID- 16423592
TI  - Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell
      function during puberty.
AB  - OBJECTIVE: To determine longitudinal changes in insulin sensitivity (SI), insulin
      secretion, and beta-cell function during puberty in white and black youth. STUDY
      DESIGN: The tolbutamide-modified frequently sampled intravenous glucose tolerance
      test and minimal modeling were used to measure SI, the acute insulin response to
      glucose (AIRg), and beta-cell function (disposition index, DI) in white (n = 46)
      and black (n = 46) children (mean [+/-SD] age at baseline = 10.2 +/- 1.7 years).
      Growth curve models (including 272 observations) with SI, AIRg, and DI regressed
      on Tanner stage were run after adjusting for covariates. RESULTS: After adjusting
      for covariates, growth curve models revealed that SI decreased and subsequently
      recovered by the end of puberty in whites and blacks (both p < .05), AIRg
      decreased linearly across Tanner stages in both races (both p < .001), and DI
      decreased across puberty in blacks (p = .001) but not in whites (p = .2).
      CONCLUSIONS: White and black youth exhibited transient insulin resistance and
      diminished AIRg during puberty. The progressive decline in DI among blacks versus
      whites may reflect a unique effect of puberty on beta-cell compensation in
      blacks. Future studies are needed to identify whether this difference contributes
      to the increased risk of type II diabetes in young blacks.

PMID- 16423594
TI  - Protective effects of the alcohol dehydrogenase-ADH1B allele in children exposed
      to alcohol during pregnancy.
AB  - OBJECTIVES: To examine alcohol use for mothers with and without an ADH1B*3 allele
      and the moderating effects of the maternal and child ADH1B*3 allele on a broad
      range of infant and 7.5-year outcomes. STUDY DESIGN: Blood samples from 263 black
      mother/child pairs (217 mothers and 239 children) were analyzed to determine
      incidence of the ADH1B allele and the relation of the maternal allele to
      pregnancy drinking assessed at every prenatal clinic visit. Moderating effects of
      ADH1B were examined by dichotomizing the moderator variable and performing
      regression analyses on the 2 groups. RESULTS: Pregnancy drinking at conception
      was less frequent in the presence of the ADH1B*3 allele, and virtually no adverse
      effects were found in children whose mothers had at least one ADH1B*3 allele. By
      contrast to the maternal allele, we found no consistent pattern of greater
      vulnerability in children lacking the ADH1B*3 allele. CONCLUSIONS: These data are
      consistent with the hypothesis that the maternal ADH1B*3 allele provides some
      protection to the fetus from prenatal alcohol exposure.

PMID- 16423595
TI  - Clinical responses of patients with Kawasaki disease to different brands of
      intravenous immunoglobulin.
AB  - OBJECTIVE: To determine whether different brands of intravenous immunoglobulin
      (IVIG) administered to children with Kawasaki disease (KD) result in different
      outcomes. STUDY DESIGN: We analyzed children with KD and divided them into 4
      groups according to the brand of IVIG. A coronary artery abnormality (CAA) was
      defined as having a lumen diameter (inner border to inner border) of > or =3 mm
      in KD cases <5 years old and > or =4 mm in cases > or =5 years old, and giant
      aneurysm was defined as a lumen diameter > or =8 mm. Patients were considered
      nonresponsive to IVIG therapy if fever persisted longer than 2 days after
      completion of treatment and needed retreatment with IVIG. RESULTS: We collected
      437 cases, 29 (6.6%) were nonresponsive, 17 (3.9%) had CAA at convalescence, and
      3 (0.7%) had giant aneurysm, 2 of whom had development of myocardial infarcts.
      Patients receiving Brand C IVIG, prepared with beta-propiolactone, had higher
      rates (10%, 9/93, P = .01) of CAA at convalescence and nonresponsiveness (13%,
      12/93, P = .001); giant aneurysm occurred in 3/93 (3%) receiving Brand C IVIG and
      in 0/344 who received the other 3 brands (P = .008). CONCLUSIONS: IVIG, prepared
      with beta-propiolactone, was most significantly associated with
      nonresponsiveness, CAA at convalescence, and giant aneurysm. Physicians should be
      cautious when using IVIG prepared with beta-propiolactone or enzyme digestion to
      treat KD.

PMID- 16423593
TI  - Insulin dynamics predict body mass index and z-score response to insulin
      suppression or sensitization pharmacotherapy in obese children.
AB  - OBJECTIVE: To assess the use of oral glucose tolerance testing (OGTT) to predict
      efficacy of insulin sensitization (metformin) or suppression (octreotide) because
      insulin resistance and insulin hypersecretion may impact pharmacotherapeutic
      efficacy in obese children. STUDY DESIGN: Forty-three and 24 obese children, with
      and without central nervous system (CNS) insult, underwent OGTT. Insulin
      sensitivity was expressed as composite insulin sensitivity index (CISI), and
      secretion as corrected insulin response (CIRgp). Those without CNS insult
      received metformin (weight-based dosing) for 6 to 16 months. Those with CNS
      insult received octreotide SQ 15 microg/kg/d for 6 months. Body mass index (BMI)
      and z-score responses were modeled using CIRgp and CISI. RESULTS: Metformin: With
      CIRgp and CISI = 1, BMI z-score in white children declined by 0.23 over the first
      4 months (P < .001), and by 0.14 over the next year (P = .33). Each 2-fold
      increase in CIRgp or CISI attenuated BMI z-score reduction, but with wide
      uncertainty (P = .24). Black children exhibited little response. Octreotide: With
      CIRgp and CISI = 1, BMI z-score decreased by 0.23 in the first 4 months (P =
      .052). Efficacy was dependent on an interaction between CIRgp and CISI (P =
      .051). CONCLUSIONS: Efficacy of metformin was predicted by pretreatment insulin
      resistance. Efficacy of octreotide was predicted by insulin hypersecretion and
      sensitivity.

PMID- 16423596
TI  - Iron sulfate supplementation decreases zinc protoporphyrin to heme ratio in
      premature infants.
AB  - OBJECTIVES: To test the utility of zinc protoporphyrin to heme ratio (ZnPP/H) as
      an indicator of iron status in premature infants and to evaluate the effect of
      oral iron supplements on oxidative injury. We hypothesized that iron sulfate
      supplementation would decrease the ZnPP/H in preterm infants. STUDY DESIGN:
      Infants eligible for this prospective study were: hospitalized, 24 to 32 weeks of
      gestation, 7 to 60 days old, feeding > or = 70 mL/kg/d, with a ZnPP/H > or = the
      mean for age. Iron dose was determined by the ZnPP/H. Iron status and oxidative
      injury were evaluated at study entry and completion. Concurrent control subjects
      met entry criteria but were not enrolled and were not treated with iron during
      the study interval. Statistical evaluation included repeated measures analysis of
      variance and Z-score conversions. RESULTS: Entry ZnPP/H of iron-treated subjects
      (n = 16) and control subjects (n = 16) were not different. The ZnPP/H of iron
      treated infants was lower at study end (P < .05) but did not change in control
      infants. Iron treatment (3 to 12 mg/kg/day) was not associated with changes in
      conventional measures of iron status nor in measures of oxidative injury.
      CONCLUSIONS: Iron sulfate supplementation (3-12 mg/kg/d) decreases ZnPP/H, is
      tolerated, and is not associated with increased oxidative injury.

PMID- 16423597
TI  - Placental circulation, fetal growth, and stiffness of the abdominal aorta in
      newborn infants.
AB  - OBJECTIVE: To measure the elastic properties of the abdominal aorta in normal
      infants and infants who had umbilical placental insufficiency (UPI) before birth.
      STUDY DESIGN: An index of aortic stiffness was measured in 65 infants who were
      appropriate-for-gestational age (32 preterm infants between 29 and 40 weeks of
      gestation) and 51 compromised infants who were identified antenatally by an
      umbilical artery Doppler flow waveform >95th percentile. An aortic stiffness
      index (SI) was measured with a phase-locked loop ultrasound technique to estimate
      the aortic systolic and diastolic diameters and their correlation with blood
      pressure. RESULTS: In normal infants, the aortic systolic and diastolic
      diameters, as well as the SI, increased with the gestational age. In the infants
      with UPI, aortic diameter and blood pressure were normal, but SI was increased.
      Infants from the compromised group with an SI >95th percentile for their
      gestational age had a significantly worse clinical outcome. CONCLUSION: The
      increase of afterload caused by UPI resulted in a decrease of aortic
      distensibility during the neonatal period, suggesting an alteration of aortic
      wall structure.

PMID- 16423598
TI  - The influence of birth weight and socioeconomic position on cognitive
      development: Does the early home and learning environment modify their effects?
AB  - OBJECTIVE: To establish whether effects of birth weight and socioeconomic
      position on cognition are explained or modified by home or learning environments.
      STUDY DESIGN: Prospective birth cohort (n = 13,980) with math tests at 7, 11, and
      16 years of age and qualifications by 33 years of age. RESULTS: For 1 kg increase
      in birth weight, 7-year math Z score increased 0.23 (0.19 adjusted for parental
      interest in child's progress) and adult qualifications increased 0.22 (on a 5
      point scale). Maternal reading benefited math less among lower than higher birth
      weights (p < .05). The birth weight effect remained unchanged 7 to 16 years of
      age. For each increment in social class (4 categories; IV&V to I&II), 7-year math
      increased 0.19 (0.12 adjusted for parental interest). Benefits of mother's
      reading and father's interest were greatest in classes IV&V (interaction p <
      .05). The difference in Z scores between classes I&II to IV&V was 0.57 at 7
      years; 1.12 at 16 years of age. Estimates were little affected by home and school
      factors. Adult qualifications increased 0.40 per unit social class (0.33 adjusted
      for parental interest). Maternal interest reduced the chances of those from
      unskilled manual origins gaining few qualifications (p < .05). Similarly,
      interactions were seen for maternal reading and paternal interest. CONCLUSION:
      Influences in the home partly underlie associations between social background and
      cognition, but they do little to explain a birth weight/cognition association.

PMID- 16423599
TI  - New insight into rectal function in pediatric defecation disorders: disturbed
      rectal compliance is an essential mechanism in pediatric constipation.
AB  - OBJECTIVE: To evaluate rectal sensitivity in patients with pediatric constipation
      (PC) and nonretentive fecal soiling (FNRFS) using pressure-controlled distention
      (barostat). STUDY DESIGN: Thresholds for rectal sensitivity (first sensation,
      urge to defecate, and pain), and rectal compliance were determined using a
      barostat. RESULTS: A total of 69 patients with PC (50 males; mean age, 10.9 +/-
      2.2 years) and 19 patients with FNRFS (15 males; mean age, 10.0 +/- 1.9 years)
      were compared with 22 healthy volunteers (HVs) (11 males; mean age, 12.7 +/- 2.6
      years). Sensitivity thresholds were not significantly different among the 3
      groups. Rectal compliance was increased in 58% of the patients with PC (P < .0001
      vs HVs). Rectal compliance did not differ between patients with FNRFS and HVs.
      Children with PC with abnormal rectal function required significantly larger
      rectal volumes at urge to defecate. CONCLUSIONS: Increased compliance is the most
      prominent feature in patients with PC. Because of higher compliance in these
      children, larger stool volumes are required to reach the intrarectal pressure of
      the urge to defecate. Children with FNRFS have normal rectal function.

PMID- 16423600
TI  - Family history is a poor screen for prothrombotic genes in children with stroke.
AB  - OBJECTIVE: To evaluate family history of early pathological thrombosis as a
      screen for genetic prothrombotic risk factors in children with stroke. STUDY
      DESIGN: A 5-year retrospective review of standardized pediatric stroke clinic
      evaluations of children with arterial ischemic stroke (AIS) or sinovenous
      thrombosis (SVT). A family history of early pathological thrombosis was defined
      as stroke, heart attack, or deep venous thrombosis before 50 years of age or
      multiple miscarriages in the parents or grandparents of the patient. We evaluated
      the association between family history and the presence of the Factor V Leiden
      mutation (FVL) and/or Prothrombin G20210A mutation (PTG) in these children.
      RESULTS: The study included 68 children. Thirteen (19.1%) had a positive family
      history of early pathological thrombosis, nine (13.2%) were heterozygous for FVL,
      and one (1.5%) was heterozygous for PTG. Family history was not associated with
      the presence of FVL (p = .36) or FVL combined with PTG (p = .40). For FVL, family
      history had a positive predictive value of 23.1% and a negative predictive value
      of 89.1%. CONCLUSION: A family history of early thrombosis is not associated with
      the presence of FVL or PTG in children with stroke. We recommend that all
      children with stroke receive a prothrombotic workup regardless of family history.

PMID- 16423601
TI  - Long-term neuromotor outcome at school entry of infants with congenital heart
      defects requiring open-heart surgery.
AB  - OBJECTIVES: Increased survival in infants with complex congenital heart defects
      (CHDs) has resulted in greater focus on morbidity. This prospective study was
      conducted to investigate whether or not neuromotor impairments evident acutely
      persist long-term. STUDY DESIGN: A total of 94 infants with CHD were reassessed
      at school entry (age 64.2 +/- 11.3 months) by blinded examiners using the Peabody
      Developmental Motor Scale and neurologic examination. RESULTS: Neurologic
      abnormalities were noted in 28.4% of the subjects, with hypotonia and
      developmental delay most commonly observed. Microcephaly was documented in 15.4%
      of subjects, with head circumference >50th percentile in only 14.1%. Mean gross
      and fine motor quotients were shifted downward (82.7 +/- 12.3 and 86.2 +/- 16.3,
      respectively), and gross and fine motor delays were prevalent (49.4% and 39.0%,
      respectively). Severe disability was rare (<5%). Predictors of neurologic
      impairment included type of surgery (palliative/corrective), abnormal
      postoperative neurologic examination, and presence of microcephaly at initial
      surgery. Gross motor delay was more likely if palliated. Deep hypothermic
      circulatory arrest time, palliative surgery, microcephaly, and number of
      hospitalizations were associated with fine motor delay. CONCLUSIONS: Neurologic
      impairments and motor delay are common in survivors of open-heart surgery,
      persisting to age of school entry. Early indicators of medical complications and
      acute neurologic compromise are associated with increased risk. Early
      identification and intervention may optimize performance in those at risk.

PMID- 16423602
TI  - Endocrinological and auxological abnormalities in young children with optic nerve
      hypoplasia: a prospective study.
AB  - OBJECTIVE: To determine the prevalence of endocrinopathies, neuroradiographical
      findings, and growth derangements in young children with optic nerve hypoplasia
      (ONH). STUDY DESIGN: A prospective observational study examined the prevalence of
      endocrinopathies at study enrollment and growth patterns in children with ONH.
      Subjects (n = 47, mean +/- SD 15.2 +/- 10.6 months) were followed until 59.0 +/-
      6.2 months of age. RESULTS: The prevalence of endocrinopathies was 71.7%: 64.1%
      of subjects had growth hormone (GH) axis abnormalities, 48.5% hyperprolactinemia,
      34.9% hypothyroidism, 17.1% adrenal insufficiency, and 4.3% diabetes insipidus
      (DI). Endocrinopathies were not associated with ONH laterality, absence of the
      septum pellucidum, or pituitary abnormalities on neuroimaging. End height
      standard deviation score (SDS) was similar to start length SDS independent of GH
      surrogate status. A significant increase in end weight SDS was found for the
      cohort (p < .001). A body mass index (BMI) >85th percentile was noted in 44.4% of
      the cohort and in 52.1% of subjects with GH axis abnormalities. Initial
      hyperprolactinemia was positively associated with increased end BMI SDS (p =
      .004). CONCLUSIONS: These prospective findings confirm the high prevalence of
      pituitary endocrinopathies in children with ONH reported in previous
      retrospective studies. Our data reveal that some of these children maintain
      normal height velocity despite GH axis abnormalities, and, as a group, they are
      at high risk for increased BMI.

PMID- 16423603
TI  - Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in
      Northwest England.
AB  - OBJECTIVE: To study the distribution of septo-optic dysplasia (SOD) and optic
      nerve hypoplasia (ONH) in the Greater Manchester and Lancashire (GM&L) region of
      Northwest England, and to analyze occurrence by location and over time. STUDY
      DESIGN: A population-based incidence study was undertaken for cases of SOD/ONH
      from GM&L. Standardized incidence ratio (SIR) for each district, relationships
      between SIRs and possible geographically varying risk factors, and spatial and
      space-time clustering were analyzed. RESULTS: Eighty-seven cases had a confirmed
      diagnosis of ONH/SOD giving an incidence of 10.9/100,000 per year in GM&L. SIRs
      ranged widely but were significantly elevated (lower confidence limit >100) in
      three districts: 167%, 192%, and 198%, respectively. All three were high
      population density, inner-city locations. SIRs were significantly correlated with
      higher rates of unemployment (r = 0.49, P = .01), dependent children in non
      earning households (r = 0.47, P = .02), underage conceptions (r = 0.46, P = .02),
      and underage pregnancies (r = 0.44, P = .03). There was no evidence of spatial or
      space-time clustering. CONCLUSIONS: The incidence of ONH/SOD in GM&L was higher
      than that reported elsewhere. Cases were more common in areas that had higher
      unemployment and teenage pregnancy rates.

PMID- 16423606
TI  - Quality of life after growth hormone therapy and induced puberty in women with
      Turner syndrome.
AB  - OBJECTIVE: To evaluate health-related quality of life (HRQoL) in young women with
      Turner syndrome (TS) after long-term growth hormone (GH) therapy and induced
      puberty and to analyze whether HRQoL was influenced by auxologic parameters,
      pubertal development, or subjective parameters. STUDY DESIGN: The study group
      comprised 49 women with TS, mean (standard deviation) age 19.6 (+/-3.0) years,
      all former participants of 2 GH studies, > or =6 months after GH discontinuation.
      Puberty was induced by estrogen treatment, at mean age 12.9 (+/-1.1) years. HRQoL
      was measured by self-reports of the 2 generic questionnaires, SF36 and TAAQOL. As
      an additional source of information on HRQoL, we applied parental proxy reports.
      RESULTS: HRQoL of the women with TS was normal. Remarkably, the women with TS had
      higher HRQoL scores on some of the scales, including "social functioning" and
      "role-emotional." Satisfaction with height and breast development had a positive
      influence on several HRQoL scales. CONCLUSIONS: The young women with TS who
      reached normal height and had age-appropriate pubertal development reported
      normal HRQoL. The relatively high scores on some of the HRQoL scales can be
      explained by an estrogen effect or by a possible response shift, indicating a
      different internal reference in women with TS. We hypothesize that GH and
      estrogen treatment positively influenced HRQoL in young women with TS.

PMID- 16423607
TI  - Truth-telling and Turner Syndrome: the importance of diagnostic disclosure.
AB  - OBJECTIVE: A targeted analysis with transcript data from previous research was
      designed to study the perceived effects of secret-keeping on individuals with
      Turner syndrome (TS). STUDY DESIGN: Girls and women (n = 97) and 21 parents
      participated in the initial interview study. Transcripts were coded and analyzed
      for constructs related to secret-keeping. RESULTS: Thirty percent of participants
      spontaneously mentioned that their health care providers (HCP) or parents had
      withheld all or part of their TS diagnosis. Of those, 15 individuals were not
      informed of the infertility component of their diagnosis. Individuals reporting
      secret-keeping were more likely to have had a negative perception of the HCP's
      role in the disclosure process compared with those participants who did not
      report that a secret had been kept (P < .025). CONCLUSION: The prevalence of
      secret-keeping within this sample population suggests it is likely an existing
      concern in the greater TS population. How HCPs disclose a TS diagnosis may affect
      whether secrets are kept. Conversely, secret-keeping may result in a negative
      disclosure experience. These observations suggest the need for interventions
      aimed at helping HCPs disclose health-related information to parents and their
      children in a timely, caring, and sensitive manner.

PMID- 16423605
TI  - Evaluation of the buserelin stimulation test in diagnosing gonadotropin
      deficiency in males with delayed puberty.
AB  - OBJECTIVE: To assess the efficacy of the gonadotropin-releasing hormone (GnRH)
      agonist buserelin in a stimulated gonadotropin test for the investigation of
      delayed puberty in males. STUDY DESIGN: Prepubertal males (n = 31; age range,
      10.3 to 17.2 years) were studied; buserelin (100 microg) was administered
      subcutaneously, with blood sampling at 0 and 4 hours for serum luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH). At follow-up (mean, 4.2
      years), 8/31 (26%) failed to progress into puberty, constituting hypogonadotropic
      hypogonadism (HH), but 23/31 (74%) had testicular enlargement (> or =8 mL)
      consistent with a normal hypothalamic-pituitary-gonadal (HPG) axis. RESULTS:
      Stimulated serum LH response to buserelin was lower in males with HH (mean +/-
      standard error under the mean for HH, 1.4 +/- 0.5 U/L, compared with a normal HPG
      axis of 17.4 +/- 2.0 U/L; P < .0001). Stimulated serum FSH response was
      nondiscriminatory (HH, 7.7 +/- 2.2 U/L; normal HPG axis, 11.5 +/- 1.6 U/L; P =
      .27). All males with HH had a stimulated serum LH level <5 U/L, whereas only 1/23
      with a normal HPG axis had a stimulated serum LH below this level. Using this
      value as the criterion for diagnosing HH, the buserelin stimulation test yielded
      a sensitivity of 100%, specificity of 96%, and positive predictive value of 89%.
      CONCLUSIONS: The buserelin stimulation test is a highly specific and sensitive
      GnRH agonist test for the investigation of males with delayed puberty.

PMID- 16423608
TI  - Outpatient pharmacotherapy for pediatric asthma.

PMID- 16423609
TI  - Skeletal dysplasia and myelopathy in congenital disorder of glycosylation type
      IA.
AB  - We report on a boy with a congenital disorder of glycosylation (CDG) Ia and a
      severe narrowing of the spinal canal caused by atlantoaxial subluxation with
      anterior displacement of C1. C1-laminectomy improved the progressive paresis.
      Progressive paresis caused by spinal cord compression is a hitherto unrecognized
      complication in patients with CDG-Ia.

PMID- 16423611
TI  - Human milk beyond one year post-partum: lower content of protein, calcium, and
      saturated very long-chain fatty acids.
AB  - Maternal milk feeding for more than 1 year is encouraged by many health care
      authorities. We demonstrate that human milk beyond 1 year of lactation had a
      small but significantly lower concentration of protein, calcium, and long-chain
      saturated fatty acids compared with human milk at 3 months after delivery.

PMID- 16423610
TI  - Cerebrospinal fluid mononuclear cell predominance is not related to symptom
      duration in children with enteroviral meningitis.
AB  - We used a binomial regression model to determine the relationship between the
      percent of cerebrospinal fluid (CSF) mononuclear white blood cells and symptom
      duration in children with proven enteroviral meningitis. The odds of a CSF white
      blood cell being mononuclear increased by 15.7% (95% confidence interval: -3.8%
      to 38.0%; P = .11) for each day of symptoms. Fifty percent of patients with
      symptoms of 1 day or less had predominance of mononuclear cells among CSF white
      blood cells. These findings suggest that factors other than symptom duration
      influence the composition and evolution of the CSF white blood cell response to
      enteroviral infection.

PMID- 16423612
TI  - Changes in amplitude-integrated electroencephalography in neonates treated with
      extracorporeal membrane oxygenation: a pilot study.
AB  - Neonates (n = 20) treated with extracorporeal membrane oxygenation were evaluated
      with serial amplitude-integrated electroencephalography (aEEG). There was no
      acute change in aEEG during extracorporeal membrane oxygenation cannulation, nor
      were there lateralizing effects. An abnormal aEEG predicted death or moderate to
      severe intracranial neuropathology with sensitivity = 1.0, specificity = 0.75,
      positive predictive value = 0.86, and negative predictive value = 1.0.

PMID- 16423613
TI  - Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in
      children.
AB  - We report the successful use of oral urea in the management of children with
      chronic syndrome of inappropriate antidiuretic hormone secretion (SIAD). We
      performed a retrospective review of four children with chronic SIAD. After
      initial attempts at management with fluid restriction, each was started on a 30%
      to 50% oral urea solution, and the dose was titrated until normal serum sodium
      was achieved. Fluid intake was liberalized after serum sodium normalization. All
      four children normalized their serum sodium. No side effects or toxicities were
      experienced. Oral urea is a safe, effective treatment for chronic SIAD in
      children.

PMID- 16423614
TI  - Abnormal oral vascular network pattern geometry: a new clinical sign of down
      syndrome.
AB  - Down syndrome is a leading genetic cause of mental retardation. Here, we show
      high fractal dimensions and Lempel-Ziv complexity and lower minimum path fractal
      dimension (P < or = .0006) for the oral vascular networks of patients (n = 14)
      and their unaffected parents. This newly recognized sign may provide a useful
      phenotypical marker for identifying couples potentially at risk for offspring
      with Down syndrome.

PMID- 16423615
TI  - Direct diagnosis of Wilson disease by molecular genetics.
AB  - In 3 children with chronic liver disease, although multiple studies of copper
      metabolism were normal, which made the diagnosis of Wilson disease unlikely,
      analysis of ATP7B gene showed disease causing mutations in all. Molecular
      diagnosis should be considered in children with enigmatic liver disease,
      especially those with features of nonalcoholic fatty liver disease.

PMID- 16423616
TI  - Early diagnosis of Wilson Disease in a six-year-old child.

PMID- 16423617
TI  - Evaluation and treatment of hepatoblastoma.

PMID- 16423618
TI  - Measurement of HbF concentration for diagnosing a case of Munchausen by proxy
      syndrome.

PMID- 16423619
TI  - Insulin resistance in hypertension quantified by oral glucose tolerance test:
      comparison of methods.
AB  - Four methods reported in the literature for evaluation of insulin sensitivity
      indexes from oral glucose tolerance tests (OGTTs) were analyzed and compared in
      order to test their ability to discriminate the insulin-resistant state in
      hypertension. To this aim, 15 normoglycemic subjects, not affected by metabolic
      syndrome, underwent a 22-sample, 300-minute OGTT. Eight subjects were
      normotensive (mean age, 47.0 +/- 4.2 years) and 7 were hypertensive (mean age,
      53.6 +/- 1.6 years). The following insulin sensitivity indexes were computed and
      compared: (a) 2 indexes, ISIE22/300 and ISIE8/180, provided by an integral
      equation (IE) method applied to the full OGTT and to a reduced 8-sample, 180
      minute data subset, respectively; (b) 2 indexes, ISOGIS180 and ISOGIS120,
      computed by the oral glucose, insulin sensitivity (OGIS) method, which only
      requires 3 blood samples taken within 180 and 120 minutes, respectively; (c) an
      index, ISISI, which considers fasting and mean insulinemia and glycemia measured
      during a 5-sample, 120-minute OGTT; and (d) an index, ISMCR, which considers body
      mass index and requires 2 blood samples taken within 120 minutes. Except the
      ISOGIS180, all other indexes were able to detect a significant reduction
      (unpaired Student t test, P < .05) of insulin sensitivity in our hypertensive
      group compared with the normotensive group. Failure of ISOGIS180 was explained by
      the fact that this index did not capture the information portrayed by the peak of
      insulinemia in hypertensive patients, which occurred around the 90th minute.
      Intraclass correlation coefficients higher than 0.89 demonstrated a substantial
      agreement between ISIE22/300 and ISIE8/180 indexes. These are the only indexes
      characterized by units of measure consistent with the definition of insulin
      sensitivity as the ability of insulin to enhance glucose effectiveness.

PMID- 16423620
TI  - NO-1886 (ibrolipim), a lipoprotein lipase-promoting agent, accelerates the
      expression of UCP3 messenger RNA and ameliorates obesity in ovariectomized rats.
AB  - The synthetic compound NO-1886 (ibrolipim, [4-(4-bromo-2-cyano-phenylcarbamoyl)
      benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase
      (LPL)-promoting agent that decreases plasma triglycerides, increases high-density
      lipoprotein cholesterol levels, and prevents fat accumulation in high fat-fed
      rats. However, the effect of NO-1886 on body weight, fat accumulation, and energy
      expenditure in ovariectomized (OVX) rats is not clear. The primary aim of this
      study was to ascertain whether NO-1886 ameliorated obesity in OVX rats and to
      examine the effects on fatty acid oxidation-related enzymes. NO-1886 decreased
      accumulation of visceral fat and suppressed the increase in body weight resulting
      from the ovariectomy. NO-1886 decreased the respiratory quotient and increased
      expression of the fatty acid translocase messenger RNA (mRNA) in the liver,
      soleus muscle, and mesenteric fat. NO-1886 also increased the expression of fatty
      acid-binding protein mRNA in the liver and soleus muscle and the expression of
      the uncoupling protein 3 (UCP3) mRNA in the heart, soleus muscle, and mesenteric
      fat, but not in the brown adipose tissue. Furthermore, NO-1886 did not affect
      UCP1 and UCP2 in brown adipose tissue. Therefore, amelioration of obesity by NO
      1886 in OVX rats is possibly because of an the increased expression of fatty acid
      oxidation-related enzymes and UCP3, both of which are related to fatty acid
      transfer and fat use. Our study indicates that the LPL-promoting agent NO-1886
      may be potentially beneficial in the treatment of obesity and obesity-linked
      health problems in postmenopausal women.

PMID- 16423622
TI  - Modifying a standard method allows simultaneous extraction of RNA and protein,
      enabling detection of enzymes in the rat retina with low expressions and protein
      levels.
AB  - The aim of the study was to evaluate messenger RNA and protein expression in
      limited amounts of tissue with low protein content. The Chomczynski method was
      used for simultaneous extraction of RNA, and protein was modified in the protein
      isolation step. Template mass and cycling time for the complementary DNA
      synthesis step of real-time reverse transcription-polymerase chain reaction (RT
      PCR) for analysis of catalase, copper/zinc superoxide dismutase, manganese
      superoxide dismutase, the catalytic subunit of glutamylcysteine ligase,
      glutathione peroxidase 1, and the endogenous control cyclophilin B (CypB) were
      optimized before PCR. Polymerase chain reaction accuracy and efficacy were
      demonstrated by calculating the regression (R2) values of the separate
      amplification curves. Appropriate antibodies, blocking buffers, and running
      conditions were established for Western blot, and protein detection and multiplex
      assays with CypB were performed for each target. During the extraction procedure,
      the protein phase was dissolved in a modified washing buffer containing 0.1%
      sodium dodecyl sulfate, followed by ultrafiltration. Enzyme expression on real
      time RT-PCR was accomplished with high reliability and reproducibility (R2, 0.990
      0.999), and all enzymes except for glutathione peroxidase 1 were detectable in
      individual retinas on Western blot. Western blot multiplexing with CypB was
      possible for all targets. In conclusion, connecting gene expression directly to
      protein levels in the individual rat retina was possible by simultaneous
      extraction of RNA and protein. Real-time RT-PCR and Western blot allowed accurate
      detection of retinal protein expressions and levels.

PMID- 16423623
TI  - Tumor necrosis factor alpha is associated with insulin-mediated suppression of
      free fatty acids and net lipid oxidation in HIV-infected patients with
      lipodystrophy.
AB  - Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined
      whether plasma TNF-alpha is associated with the degree by which insulin
      suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and
      net lipid oxidation (LIPOX) rate in HIV-infected patients with lipodystrophy
      (LIPO) and those without (controls). LIPOX was estimated by indirect calorimetry
      during fasting and steady state of a hyperinsulinemic euglycemic clamp in 36 (18
      LIPO and 18 controls) normoglycemic HIV-infected men on highly active
      antiretroviral therapy. In LIPO, TNF-alpha correlated with clamp FFA (r = 0.67, P
      < .01), clamp LIPOX (r = 0.47, P < .05), incremental FFA (r = 0.69, P < .01), and
      incremental LIPOX (r = 0.64, P < .01), all of which, but not the clamp LIPOX
      correlation (r = 0.29, P > .05), remained significant after correction for
      insulin sensitivity. None of these correlations were significant in controls. In
      all patients, TNF-alpha correlated with clamp FFA (r = 0.61, P < .001), clamp
      LIPOX (r = 0.43, P < .01), and incremental FFA (r = 0.43, P < .01), with the 2
      former correlations remaining significant after correction for insulin
      sensitivity. LIPOX and FFA (fasting and clamp values combined) correlated
      strongly and positively in both LIPO (R2 = 0.43, P < .001) and controls (R2 =
      0.60, P < .0001). Fasting FFA and LIPOX did not differ between study groups;
      however, the insulin-mediated suppression of FFA and LIPOX was attenuated in LIPO
      (P's < .05). Our data indicate that higher TNF-alpha, independently of insulin
      sensitivity, is associated with attenuated insulin-mediated suppression of FFA
      and LIPOX in HIV-LIPO, suggesting in turn that TNF-alpha stimulates lipolysis in
      this syndrome. Furthermore, FFA may be a major determinant of LIPOX in HIV
      infected patients on highly active antiretroviral therapy.

PMID- 16423621
TI  - Ascorbic acid and alpha-tocopherol down-regulate apolipoprotein A-I gene
      expression in HepG2 and Caco-2 cell lines.
AB  - HepG2 cells and Caco-2 cells were treated with various concentrations of select
      antioxidants to study some of the molecular pathways underlying antioxidant
      related changes in apolipoprotein A-I (apoA-I) expression. Both alpha-tocopherol
      and ascorbate treatment over a time course of 72 hours caused a significant
      reduction in apoA-I messenger RNA and protein levels in a dose-dependent fashion.
      Albumin levels did not change with any treatment, suggesting that the effect is
      protein-specific. Similar changes were seen in Caco-2 cells. In contrast, apoA-I
      messenger RNA and protein levels significantly increased after 28 and 280
      micromol/L dimethyl sulfoxide (DMSO) treatment. Cells were transfected with
      chloramphenicol acetyltransferase (CAT) reporter gene plasmid containing the full
      length apoA-I promoter to determine if these changes occur at a transcriptional
      level, and after 24 hours, the HepG2 or Caco-2 cells were treated with varying
      concentrations of ascorbate or alpha-tocopherol. At the highest concentration of
      ascorbate and alpha-tocopherol used (5 mmol/L), there was a significant reduction
      in apoA-I promoter activity. DMSO treatment up-regulated apoA-I promoter
      activity, whereas increasing oxidative load with 50, 100, and 200 micromol/L
      hydrogen peroxide treatment did not significantly alter apoA-I promoter activity.
      Studies with deletional constructs of the promoter containing or lacking the
      antioxidant response element (ARE) indicated that the effect of ascorbate and
      alpha-tocopherol, unlike that of DMSO, was independent of this ARE. Using a
      series of apoA-I deletion constructs, it was shown that site A-containing segment
      of the promoter has a critical regulatory element. However, electromobility shift
      assays indicated that there was no significant change in nuclear factor binding
      activity to site A as a result of treatment with ascorbate or alpha-tocopherol.
      As expected, treatment with DMSO increased factor binding to the previously
      described ARE. It is concluded that the apoA-I promoter-stimulating effect of
      DMSO may be independent of its antioxidant activity and that some antioxidants at
      very high concentrations may have suppressive effect on the apoA-I gene
      expression. It appears that the inhibitory effect of ascorbate or alpha
      tocopherol on the apoA-I promoter is either indirect or is the result of
      posttranslational modifications of the nuclear binding factors. The previously
      described ARE is not a response element for the ascorbate or alpha-tocopherol.

PMID- 16423624
TI  - Comparison of insulin resistance and serum high-sensitivity C-reactive protein
      levels according to the fasting blood glucose subgroups divided by the newly
      recommended criteria for fasting hyperglycemia in 10059 healthy Koreans.
AB  - The increment for the prevalence of diabetes mellitus and impaired glucose
      tolerance warrants lowering the cutoffs of normoglycemia to help predict the
      future development of diabetes. The aim of this study was to find out whether
      insulin resistance and high-sensitivity C-reactive protein (hsCRP), a
      nontraditional cardiovascular risk factor, were related to the fasting glucose
      level, even in normoglycemic range that was categorized by the newly recommended
      criteria by the American Diabetes Association. Among the participants undergoing
      medical checkup program at Kangbuk Samsung Hospital, 10059 subjects (5535 men and
      4524 women; mean age, 45 years) with normal fasting glucose levels, as defined by
      the newly recommended criteria (<5.6 mmol/L), were enrolled in this study. The
      blood pressures, body mass index (BMI), fasting blood glucose, fasting insulin,
      lipid batteries, and hsCRP levels were checked. The homeostatic model assessment
      insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check
      indexes (QUICKI) were calculated. All subjects were subdivided into 4 groups
      according to the fasting glucose level. The HOMA-IR, QUICKI, and log-transformed
      (log) hsCRP, or log(hsCRP), level significantly increased according to the
      increment in fasting glucose, and these associations were consistent after
      adjustment for age and BMI, except for the log(hsCRP) (P = .124 after
      adjustment). Log(hsCRP) increased as the HOMA-IR increased and as the QUICKI
      decreased, and when multiple regression analysis was done with log(hsCRP) as the
      dependent variable, age, high BMI, male sex, high HOMA-IR, hypertriglyceridemia,
      and low high-density lipoprotein cholesterol were the significant predictor for
      log(hsCRP). In conclusion, the insulin resistance indexes and hsCRP increased
      gradually even in the normal fasting glucose range, as categorized by the newly
      recommended criteria for abnormal fasting glucose levels, supporting the
      rationale for expanding the range of fasting hyperglycemia.

PMID- 16423625
TI  - Serum adiponectin in a population sample of 64-year-old women in relation to
      glucose tolerance, family history of diabetes, autoimmunity, insulin sensitivity,
      C-peptide, and inflammation.
AB  - The aim of the study was to describe serum adiponectin levels in a population
      based sample of women with different degrees of glucose tolerance and to examine
      if the variability in serum adiponectin was explained by family history of
      diabetes, obesity, insulin resistance, glycemia, and inflammation. Repeated oral
      glucose tolerance tests were used in a screening procedure of a cohort of 64-year
      old women to identify those with diabetes mellitus n = 210) and impaired glucose
      tolerance (n = 201). A random sample of women with normal glucose tolerance (NGT,
      n = 186) was also included. The examination included history of first-degree
      relatives with diabetes, anthropometry, measurement of circulating adiponectin,
      glutamic acid decarboxylase antibodies, blood glucose, HbA1c, insulin,
      proinsulin, C-peptide, high-sensitivity C-reactive protein, and homeostasis model
      assessment. Serum adiponectin concentration was lowest among diabetic women,
      highest in the random-sample NGT group, and intermediate in the impaired glucose
      tolerance group. This difference was partly explained by homeostasis model
      assessment, C-peptide, family history, and high-sensitivity C-reactive protein
      (R2 = 0.33, P < .001), but obesity and glycemia did not contribute to this
      variability in serum adiponectin. A family history of diabetes was associated
      with low serum adiponectin concentration independently of obesity, glycemia, or
      insulin sensitivity (P = .002). Glutamic acid decarboxylase-positive diabetic
      women (n = 17) had similar serum adiponectin as the NGT group in spite of
      hyperglycemia. In conclusion, serum adiponectin was lowered in women with type 2
      diabetes mellitus, and this difference could only be partly explained by insulin
      resistance, insulin secretion, family history of diabetes, and inflammation.
      Family history of diabetes was independently associated with hypoadiponectinemia.
      Autoimmune diabetic women did not have low adiponectin levels.

PMID- 16423626
TI  - The effects of a new soluble dietary fiber on weight gain and selected blood
      parameters in rats.
AB  - This study was designed to investigate a new dietary fiber, alpha-cyclodextrin,
      marketed under the trade name FBCx (Wacker Biochem, Adrian, MI), for beneficial
      effects on weight reduction and the improvement of certain blood parameters in
      rats. Male Wistar rats were divided into 4 groups and fed ad libitum for a period
      of 6 weeks: (1) a normal low-fat diet (LF; 4% fat wt/wt); (2) an LF diet with
      FBCx added; (3) a high-fat diet (HF, 40% fat wt/wt); and (4) an HF diet with
      FBCx. The FBCx was added at the rate of 10% (wt/wt) of the fat in the diet. Body
      weight and food intake were recorded 3 times per week. Plasma constituent levels
      and liver and fecal lipid contents, as well as body composition were determined
      at sacrifice. Adding FBCx to the diet significantly reduced weight gain in rats
      fed with an HF diet relative to rats fed with the HF control diet (P < .05). FBCx
      also elicited a reduction in plasma triglyceride levels of 30%, total cholesterol
      of 9%, and increased the fat content of the feces in the rats fed with the HF
      diet with FBCx. In addition, the serum leptin levels were normalized, and the
      calculated insulin sensitivity was improved. No adverse effects were observed in
      the rats consuming FBCx. It would appear that FBCx might be effective in reducing
      body weight gain and improving metabolic syndrome.

PMID- 16423628
TI  - The Arg121Trp variant in PAX4 gene is associated with beta-cell dysfunction in
      Japanese subjects with type 2 diabetes mellitus.
AB  - Mutations in PAX4, a transcription factor involved in the beta-cell
      differentiation, could predispose to the development of type 2 diabetes mellitus.
      To clarify the role of PAX4 Arg121Trp mutation on the development of type 2
      diabetes mellitus, we try to determine the clinical phenotype in diabetic
      subjects with this mutation. Study subjects consisted of 793 type 2 diabetic
      patients and 318 control subjects. Genotyping for Arg121Trp polymorphism was
      performed by Invader assay. Clinical phenotype was determined in diabetic
      subjects including 20 Trp121 carriers and 142 wild-type subjects using a
      combination of 2-compartment model of C-peptide kinetics and minimal model
      analysis during intravenous glucose tolerance test. We detected 3 Trp/Trp, 51
      Arg/Trp, and 739 Arg/Arg in diabetic subjects, and 16 Arg/Trp and 302 Arg/Arg in
      control subjects. The frequency of Trp121 allele was 3.59% and 2.51% in diabetic
      and control groups, respectively (P = .19). Rate of insulin users was higher in
      Trp121 carriers compared with the wild-type group (42.5% vs 25.0%, P = .0046).
      First-phase C-peptide secretion was significantly decreased in the diabetic
      subjects with Trp121 allele compared with the patients with wild type (P =
      .0048), whereas there were no significant differences in insulin sensitivity and
      glucose effectiveness between the groups. Arg121Trp mutation in PAX4 gene could
      be associated with beta-cell dysfunction in Japanese subjects with type 2
      diabetes mellitus.

PMID- 16423627
TI  - High-fat feeding effects on components of the CAP/Cbl signaling cascade in
      Sprague-Dawley rat skeletal muscle.
AB  - The aim of this investigation was to determine whether the CAP (Cbl-associated
      protein)/Cbl signaling cascade is present and responsive to insulin in skeletal
      muscle and if high-fat feeding impairs insulin-stimulated activation of this
      signaling cascade. Sprague-Dawley rats were assigned to either control (n = 16)
      or high fat-fed (n = 16) dietary groups. After a 12-week dietary period, animals
      were subjected to hind limb perfusions in the presence (n = 8 per group) or
      absence (n = 8 per group) of insulin. High-fat feeding reduced rates of insulin
      stimulated skeletal muscle phosphatidylinositol 3-kinase activity and 3-O
      methylglucose transport. In plasma membrane fractions, neither the high-fat diet
      nor insulin altered the insulin receptor beta subunit (IR-beta), APS (adaptor
      protein containing PH and SH2 domains), c-Cbl, or TC10 protein concentration, but
      high-fat feeding did decrease CAP protein concentration. APS, c-Cbl, CAP, and
      TC10 messenger RNA were present in the skeletal muscle and reflected the protein
      concentration of experimental groups. Despite insulin-stimulated plasma membrane
      IR-beta tyrosine phosphorylation being unaffected by high-fat feeding, c-Cbl
      tyrosine phosphorylation, the kinase activity of IR-beta toward APS, and glucose
      transporter 4 protein concentration were all significantly reduced in insulin
      stimulated plasma membrane prepared from the skeletal muscle of high fat-fed
      animals. These findings suggest that the CAP/Cbl signaling cascade is present in
      skeletal muscle, activated by insulin, and impaired by high-fat feeding.

PMID- 16423629
TI  - Repeated prolonged whole-body low-intensity exercise: effects on insulin
      sensitivity and limb muscle adaptations.
AB  - This study investigates the effect of prolonged whole-body low-intensity exercise
      on insulin sensitivity and the limb muscle adaptive response. Seven male subjects
      (weight, 90.2 +/- 3.2 kg; age, 35 +/- 3 years) completed a 32-day unsupported
      crossing of the Greenland icecap on cross-country skies pulling sleighs. The
      subjects were studied before and 3 to 4 days after the crossing of the icecap.
      Subjects came in overnight fasted, and an intravenous glucose tolerance test
      (IVGTT) was done. A biopsy was obtained from the vastus lateralis and deltoid
      muscle. On a separate day, a progressive test was performed to establish maximal
      oxygen uptake. During the crossing, subjects skied for 342 +/- 41 min/d. Peak
      oxygen uptake (4.6 +/- 0.2 L/min) was decreased (P < .05) by 7% after the
      crossing and body mass decreased (P < .05) by 7.1 +/- 0.2 kg, of which 4.4 +/-
      0.5 kg was fat mass and 2.7 +/- 0.2 kg lean body mass. Glycosylated hemoglobin
      (5.6% +/- 0.01%) was not affected by the crossing. The IVGTT data revealed that
      insulin sensitivity (7.3 +/- 0.6 mU x L-1 x min-1) and glucose effectiveness
      (0.024 +/- 0.002 min-1) were not changed after the crossing. Similarly, the IVGTT
      data, when expressed per kilogram of lean body mass or body mass, were not
      affected by the crossing. Citrate synthase activity was higher (P < .05) in the
      leg (29 +/- 1 micromol x g-1 x min-1) than in the arm muscle (16 +/- 2 micromol x
      g-1 x min-1) and was unchanged after the crossing. Muscle GLUT4 protein
      concentration was higher (P < .05) in the leg (104 +/- 10 arbitrary units) than
      in the arm (54 +/- 9 arbitrary units) and was not changed in the leg, but was
      increased (P < .05) by 70% to 91 +/- 9 arbitrary units in the arm after the
      crossing. In conclusion, the increased glucose transporter expression in arm
      muscle may compensate for the loss of lean body mass and the decrease in aerobic
      fitness and thereby contribute to the maintenance of whole-body insulin
      sensitivity after prolonged low-intensity exercise training.

PMID- 16423630
TI  - Hazards associated with pregnancies and deliveries in lysinuric protein
      intolerance.
AB  - Lysinuric protein intolerance (LPI) is an autosomal recessive transport disorder
      of the dibasic amino acids. The defect leads to deficiency of lysine, arginine,
      and ornithine and, secondarily, to a functional disorder of the urea cycle.
      Transient postprandial hyperammonemia and subsequent persistent protein aversion,
      linked with several other biochemical and clinical characteristics of the
      disease, suggest an increased risk for maternal and fetal complications during
      pregnancy and delivery. Our unique material on the outcomes of 18 pregnancies of
      9 Finnish mothers with LPI and the follow-up of their 19 children shows that
      maternal LPI is truly associated with increased risk of anemia, toxemia, and
      intrauterine growth retardation during pregnancy and bleeding complications
      during delivery. Successful pregnancies and deliveries can still be achieved with
      careful follow-up of blood pressure and laboratory values. The children of the
      mothers with LPI generally develop normally. Special care of maternal protein
      nutrition and control of ammonemia, anemia, and toxemia during pregnancy are
      essential. We propose centralization of deliveries to obstetric units with
      capability to deal with bleeding complications and rare inborn errors of
      metabolism.

PMID- 16423631
TI  - Increased serum levels of the specific advanced glycation end product
      methylglyoxal-derived hydroimidazolone are associated with retinopathy in
      patients with type 2 diabetes mellitus.
AB  - Advanced glycation end products (AGEs) are thought to play a major pathogenic
      role in diabetic retinopathy. The most important AGE is unknown, but as increased
      serum methylglyoxal-derived hydroimidazolone has been demonstrated in patients
      with type 2 diabetes mellitus, the aim of the present study was to elucidate
      possible associations between serum levels of hydroimidazolone and retinopathy in
      patients with type 2 diabetes mellitus. We recruited 227 patients with type 2
      diabetes mellitus and retinopathy ranging from none to proliferative. Level of
      retinopathy was determined from 7 standard field stereo photographs per eye
      according to the Early Treatment Diabetic Retinopathy Study. The patients were 66
      +/- 11 years old, with a known diabetes duration of 14 +/- 9 years. Serum levels
      of hydroimidazolone were determined with a competitive immunoassay. Serum levels
      of hydroimidazolone were increased in nonproliferative (median, 4.50 U/mL;
      interquartile range, 3.69-5.77 U/mL) and proliferative retinopathy (median, 4.88
      U/mL; interquartile range, 3.70-6.52 U/mL) compared with patients without
      retinopathy (median, 4.02 U/mL; interquartile range, 3.47-4.88 U/mL) (P = .008
      and .002, respectively). There was no association between hydroimidazolone and
      hemoglobin A1c (r = 0.04, P = .57). In addition, patients with proliferative
      retinopathy and a relatively short known duration of diabetes, that is, less than
      the median of 14 years, had increased serum levels of hydroimidazolone (median,
      6.91 U/mL; interquartile range, 4.70-8.91 U/mL) compared with those with
      nonproliferative retinopathy (median, 4.34; interquartile range, 3.86-5.53U/mL, P
      = .015). Serum levels of hydroimidazolone are increased in type 2 diabetic
      patients with retinopathy. This association is independent of hitherto known
      associated factors, such as hemoglobin A1c.

PMID- 16423632
TI  - Soluble P-selectin and CD40L levels in subjects with prediabetes, diabetes
      mellitus, and metabolic syndrome--the Chennai Urban Rural Epidemiology Study.
AB  - The aim of the study was to determine whether the levels of soluble P-selectin
      (sP-selectin) and soluble CD40L (sCD40L) are elevated in Asian Indian subjects
      with impaired glucose tolerance (IGT), diabetes, and metabolic syndrome (MS).
      Study subjects were recruited from the Chennai Urban Rural Epidemiology Study
      (CURES), an ongoing population-based study on a representative population of
      Chennai city in southern India, and were grouped as follows: group 1, normal
      glucose tolerance (NGT) (n = 60); group 2, IGT (n = 60); and group 3, type 2
      diabetes mellitus (n = 60). Normal glucose tolerance, IGT, and diabetes were
      defined using World Health Organization consulting group criteria. The inclusion
      criteria were nonsmokers; normal resting 12-lead electrocardiogram; absence of
      angina, myocardial infarction, or history of any known vascular, infectious, or
      inflammatory diseases; and subjects not on statins or aspirin. Insulin resistance
      was calculated using the homeostasis assessment model using the formula: fasting
      insulin (microIU/mL) x fasting glucose (mmol/L)/22.5. Soluble P-selectin and
      sCD40L were estimated by enzyme-linked immunosorbent assay. Metabolic syndrome
      was defined using Adult Treatment Panel III guidelines. Subjects with diabetes
      and IGT were older (diabetes: 53 +/- 9 years, P < .01; IGT: 51 +/- 10 years, P <
      .05) compared with the NGT group (48 +/- 10 years). Subjects with diabetes and
      IGT had higher levels of sP-selectin (diabetes: 162 +/- 79 ng/mL, P < .001; IGT:
      102 +/- 37 ng/mL, P < .001) compared with the NGT group (55 +/- 48 ng/mL).
      Soluble CD40L levels were also higher in those with diabetes and IGT (diabetes:
      3.2 +/- 2.0 ng/mL, P < .001; IGT: 2.0 +/- 1.3 ng/mL, P < .001) compared with the
      NGT group (1.1 +/- 0.9 ng/mL). Subjects with MS had significantly higher levels
      of sP-selectin (with MS, 118 +/- 76 ng/mL; without MS, 95 +/- 66 ng/mL; P = .028)
      and sCD40L (with MS, 2.4 +/- 1.8 ng/mL; without MS, 1.9 +/- 1.5 ng/mL; P = .036)
      compared with subjects without MS. Among subjects with NGT and IGT, the mean
      levels of sP-selectin (tertile I, 65.0 ng/mL; tertile II, 80.0 ng/mL; tertile
      III, 91.0 ng/mL) and sCD40L levels (tertile I, 1.2 ng/mL; tertile II, 1.7 ng/mL;
      tertile III, 1.8 ng/mL) increased with increase in tertiles of homeostasis
      assessment model-insulin resistance, and the difference reached statistical
      significance in the last tertile compared with the first tertile (P < .05). This
      study demonstrates that increased levels of sP-selectin and sCD40L are seen in
      Asian Indian subjects with IGT, type 2 diabetes mellitus, MS, and insulin
      resistance.

PMID- 16423633
TI  - The metabolic response to a high-protein, low-carbohydrate diet in men with type
      2 diabetes mellitus.
AB  - We recently reported that in subjects with untreated type 2 diabetes mellitus, a
      5-week diet of 20:30:50 carbohydrate-protein-fat ratio resulted in a dramatic
      decrease in 24-hour integrated glucose and total glycohemoglobin compared with a
      control diet of 55:15:30. Body weight, total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and serum ketones were
      unchanged; insulin and nonesterified fatty acids were decreased. We now present
      data on other hormones and metabolites considered to be affected by dietary
      macronutrient changes. The test diet resulted in an elevated fasting plasma total
      insulin-like growth factor 1, but not growth hormone. Urinary aldosterone was
      unchanged; free cortisol was increased, although not statistically. Urinary pH
      and calcium were unchanged. Blood pressure, creatinine clearance, serum vitamin
      B12, folate, homocysteine, thyroid hormones, and uric acid were unchanged. Serum
      creatinine was modestly increased. Plasma alpha-amino nitrogen and urea nitrogen
      were increased. Urea production rate was increased such that a new steady state
      was present. The calculated urea production rate accounted for 87% of protein
      ingested on the control diet, but only 67% on the test diet, suggesting net
      nitrogen retention on the latter. The lack of negative effects, improved glucose
      control, and a positive nitrogen balance suggest beneficial effects for subjects
      with type 2 diabetes mellitus at risk for loss of lean body mass.

PMID- 16423634
TI  - Relationship between plasma S-adenosylhomocysteine concentration and glomerular
      filtration rate in children.
AB  - S-Adenosylhomocysteine (SAH) is the metabolic precursor of all the homocysteine
      (Hcy) produced in the body. It is formed by the enzyme SAH hydrolase in a
      reversible reaction. In a previous study we have shown that plasma SAH is a more
      sensitive indicator of the risk for cardiovascular disease, and in a second study
      involving patients with renal disease, we also showed that it is a more sensitive
      indicator of renal insufficiency than plasma Hcy. However, in the latter study,
      the patients with renal disease were older and had a variety of other diseases
      such as diabetes and primary hypertension, which are associated with vascular
      disease and which could reduce renal function by involvement of the kidneys. Our
      objective was to rule out these complicating factors as the cause of the elevated
      SAH in renal disease and determine whether renal insufficiency alone was the
      cause of the elevated SAH. We therefore measured SAH, Hcy, folate, and vitamin
      B12 in 23 patients between the ages of 1 and 18 years with a wide range of renal
      function, but who had none of these complicating factors. Glomerular filtration
      rate (GFR) was calculated using serum creatinine according to the Schwartz
      formula. None of the children were deficient in folate or vitamin B12. After
      adjusting for age, folate, and vitamin B12, there was a modest and insignificant
      decrease of 0.033 micromol/L of Hcy associated with an increase of 1 mL/min of
      GFR (95% confidence interval, -0.066 to 0.0002). However, there was a strong and
      statistically significant association between log(SAH) and log(GFR): P < .0005,
      R2 = 0.76. This result suggests that plasma SAH rather than Hcy is the metabolite
      primarily affected in renal disease. We suggest that plasma Hcy elevations that
      have been linked to vascular disease may be due to elevated SAH resulting from
      renal insufficiency.

PMID- 16423635
TI  - Interleukin 6, adiponectin, leptin, and insulin resistance in nonobese Japanese
      type 2 diabetic patients.
AB  - The aim of the present study was to investigate the relationships between
      interleukin 6 (IL-6) and insulin resistance, serum leptin, serum adiponectin, or
      serum lipids including triglycerides in 98 nonobese Japanese type 2 diabetic
      patients. Insulin resistance was estimated by the insulin resistance index of
      homeostasis model assessment (HOMA-IR). Serum IL-6 concentration was negatively
      correlated to high-density lipoprotein cholesterol (r = -0.295, P = .004), but
      was not associated with HOMA-IR (r = 0.016, P = .871), body mass index (BMI) (r =
      0.090, P = .375), systolic (r = 0.169, P = .116) and diastolic (r = -0.061, P =
      .570) blood pressures, leptin (r = 0.062, P = .544), and adiponectin (r = -0.020,
      P = .841) in these patients. In contrast, serum leptin level was positively
      correlated to HOMA-IR (r = 0.291, P = .004), BMI (r = 0.338, P < .001), and
      systolic blood pressure (r = 0.241, P = .025). Serum adiponectin level was
      negatively correlated to HOMA-IR (r = -0.288, P = .005), BMI (r = -0.308, P =
      .002), diastolic blood pressure (r = -0.269, P = .012), and triglycerides (r = 
      0.338, P < .001), and positively correlated to high-density lipoprotein
      cholesterol (r = 0.300, P = .003) in our patients. From these results, it can be
      suggested that fasting serum IL-6 is not a major factor responsible for the
      evolution of insulin resistance in nonobese Japanese type 2 diabetic patients.

PMID- 16423636
TI  - Short-term bioaccumulation of vanadium when ingested with a tea decoction in
      streptozotocin-induced diabetic rats.
AB  - Sodium orthovanadate suspended in a lichee black tea decoction effectively
      regulates blood glucose levels in rats with insulin-dependent, streptozotocin
      (STZ)-induced diabetes. The primary advantage of vanadate delivery with the tea
      decoction over conventional systems that use water suspensions of vanadate is a
      significant reduction in the toxic side effects of vanadate. It is unknown if the
      tea alters the bioavailability of vanadate. Male Sprague-Dawley rats were
      administered an intravenous injection of STZ to induce diabetes. Four days later,
      the diabetic rats were treated by oral gavage with 40 mg of Na-orthovanadate
      suspended in double-distilled, deionized water (V/H2O), tea/vanadate (TV)
      decoction, or were treated with the tea decoction alone. Vanadium concentrations
      were measured in blood and various tissues at 1 to 24 hours posttreatment using
      graphite furnace atomic absorption spectrophotometry. With the exception of bone,
      maximal vanadium concentration in plasma and tissue samples were observed 2 hours
      after ingestion, but steadily decreased after that. Plasma vanadium levels
      continued to decrease until 16 hours. In contrast, vanadium steadily accumulated
      in bone over the 24-hour period. Overall, rats treated with V/H2O contained
      similar or significantly higher concentrations of vanadium in all tissues
      compared with TV treatment. The pattern of vanadium accumulation was also similar
      over time in both treatment groups. Vanadium levels were highest in bone > kidney
      > liver > pancreas > lung > heart > muscle > brain in both TV- and V/H2O-treated
      animals. This study demonstrates that the accumulation of vanadium in diabetic
      rats is reduced when coadministered with a black tea decoction in comparison to
      administration of vanadium in water. However, this effect is unlikely to be of a
      magnitude to explain the full capacity of TV to reduce the toxic side effects of
      vanadate.

PMID- 16423637
TI  - Altered tumor necrosis factor alpha release from mononuclear cells of obese
      reproductive-age women during hyperglycemia.
AB  - The aim of the study was to determine whether lipopolysaccharide (LPS)-stimulated
      tumor necrosis factor alpha (TNF-alpha) release from mononuclear cells (MNCs) is
      altered in obese reproductive-age women in response to hyperglycemia. Six obese
      and 8 age-matched normal-weight women (18-40 years) underwent a 2-hour 75-g oral
      glucose tolerance test. Tumor necrosis factor alpha release was measured from
      MNCs cultured in the presence of LPS after isolation from blood samples drawn
      fasting and 2 hours after glucose ingestion. Insulin resistance was derived by
      homeostasis model assessment of insulin resistance. Total body fat (%) and
      truncal fat (%) were determined by dual-energy absorptiometry. Obese women had a
      higher (P < .03) body mass index (34.1 +/- 1.1 vs 21.9 +/- 0.8 kg/m2), percentage
      of total body fat (42.4% +/- 1.3% vs 28.7% +/- 1.8%), and percentage of truncal
      fat (42.1% +/- 1.2% vs 24.7% +/- 2.2%). Homeostasis model assessment of insulin
      resistance was greater in the obese group (58.0 +/- 10.6 vs 27.8 +/- 4.3, P <
      .02). Fasting plasma C-reactive protein (7787 +/- 884 vs 236 +/- 79 ng/mL, P <
      .0001) and TNF-alpha (2.37 +/- 0.09 vs 0.54 +/- 0.04 pg/mL, P < .05) were both
      elevated in obese women. Hyperglycemia resulted in a suppression of LPS
      stimulated TNF-alpha release from MNCs of normal-weight subjects (154 +/- 21 vs
      57 +/- 28 pg/mL, P < .003), but no change in obese women (148 +/- 36 vs 173 +/-
      49 pg/mL). The TNF-alpha response was different between groups (-97 +/- 21 vs +24
      +/- 22 pg/mL, P < .003). There was also a positive association between the
      incremental change in MNC-derived TNF-alpha and percentage of truncal fat (r =
      0.75, P < .002). In conclusion, these data suggest that there is an absence of
      the "normal" suppression of TNF-alpha in MNCs after hyperglycemia in obese women,
      and this response may contribute to impaired glucose disposal and insulin
      resistance.

PMID- 16423638
TI  - Letter to the editor.

PMID- 16423641
TI  - Case closed.

PMID- 16423642
TI  - The new wave of ePCRs.

PMID- 16423643
TI  - Talking trash. Where do you throw stuff?

PMID- 16423644
TI  - Offshore innovation.

PMID- 16423645
TI  - What we know about the EMS workforce.

PMID- 16423647
TI  - Do EMS ride-along programs violate patient privacy? How to ensure your program
      measures up to HIPAA's privacy rule.

PMID- 16423649
TI  - Follow-up EMS visits.

PMID- 16423650
TI  - Bacterial tyrosinases.
AB  - Tyrosinases are nearly ubiquitously distributed in all domains of life. They are
      essential for pigmentation and are important factors in wound healing and primary
      immune response. Their active site is characterized by a pair of
      antiferromagnetically coupled copper ions, CuA and CuB, which are coordinated by
      six histidine residues. Such a "type 3 copper centre" is the common feature of
      tyrosinases, catecholoxidases and haemocycanins. It is also one of several other
      copper types found in the multi-copper oxidases (ascorbate oxidase, laccase). The
      copper pair of tyrosinases binds one molecule of atmospheric oxygen to catalyse
      two different kinds of enzymatic reactions: (1) the ortho-hydroxylation of
      monophenols (cresolase activity) and (2) the oxidation of o-diphenols to o
      diquinones (catecholase activity). The best-known function is the formation of
      melanins from L-tyrosine via L-dihydroxyphenylalanine (L-dopa). The complicated
      hydroxylation mechanism at the active centre is still not completely understood,
      because nothing is known about their tertiary structure. One main reason for this
      deficit is that hitherto tyrosinases from eukaryotic sources could not be
      isolated in sufficient quantities and purities for detailed structural studies.
      This is not the case for prokaryotic tyrosinases from different Streptomyces
      species, having been intensively characterized genetically and spectroscopically
      for decades. The Streptomyces tyrosinases are non-modified monomeric proteins
      with a low molecular mass of ca. 30kDa. They are secreted to the surrounding
      medium, where they are involved in extracellular melanin production. In the
      species Streptomyces, the tyrosinase gene is part of the melC operon. Next to the
      tyrosinase gene (melC2), this operon contains an additional ORF called melC1,
      which is essential for the correct expression of the enzyme. This review
      summarizes the present knowledge of bacterial tyrosinases, which are promising
      models in order to get more insights in structure, enzymatic reactions and
      functions of "type 3 copper" proteins in general.

PMID- 16423651
TI  - Distribution of F- and A/V-type ATPases in Thermus scotoductus and other closely
      related species.
AB  - The presence of an A/V-type ATPase in different Thermus species and in the deeper
      branching species Meiothermus ruber and Deinococcus radiodurans suggests that the
      presence of the archaeal-type ATPase is a primitive character of the Deinococci
      that was acquired through horizontal gene transfer (HGT). However, the presence
      of a bacterial type F-ATPases was reported in two newly identified Thermus
      species (Thermus scotoductus DSM 8553 and Thermus filiformis DSM 4687). Two
      different scenarios can explain this finding, either the recent replacement of
      the ancestral A/V-type ATPase in Thermus scotoductus and Thermus filiformis with
      a newly acquired F-type ATPase or a long-term persistence of both F and A type
      ATPase in the Deinococci, which would imply several independent losses of the F
      type ATPase in the Deinococci. Using PCR with redundant primers, sequencing and
      Southern blot analyses, we tried to confirm the presence of an F-type ATPase in
      the genome of Thermus scotoductus and Thermus filiformis, and determine its
      phylogenetic affinities. Initial experiments appeared to confirm the presence of
      an F-type ATPase in Thermus scotoductus that was similar to the F-ATPases found
      in Bacillus. However, further experiments revealed that the detection of an F
      ATPase was due to a culture contamination. For all the Thermus and Deinococcus
      species surveyed, including Thermus scotoductus, cultures that were free of
      contamination only contained an A/V-type ATP synthases.

PMID- 16423652
TI  - Growth characteristics of Bacillus anthracis compared to other Bacillus spp. on
      the selective nutrient media Anthrax Blood Agar and Cereus Ident Agar.
AB  - Anthrax Blood Agar (ABA) and Cereus Ident Agar (CEI) were evaluated as selective
      growth media for the isolation of Bacillus anthracis using 92 B. anthracis and
      132 other Bacillus strains from 30 species. The positive predictive values for
      the identification of B. anthracis on ABA, CEI, and the combination of both were
      72%, 71%, and 90%, respectively. Thus, less than 10% of all species were
      misidentified using both nutrient media. Species which might be misidentified as
      B. anthracis were B. cereus, B. mycoides, and B. thuringiensis. Particularly, 30%
      of B. weihenstephanensis strains were misidentified as B. anthracis.

PMID- 16423654
TI  - Evaluation of amplified ribosomal DNA restriction analysis (ARDRA) and species
      specific PCR for identification of Bifidobacterium species.
AB  - Molecular biological methods based on genus-specific PCR, species-specific PCR,
      and amplified ribosomal DNA restriction analysis (ARDRA) of two PCR amplicons
      (523 and 914bp) using six restriction enzymes were used to differentiate among
      species of Bifidobacterium. The techniques were established using DNA from 16
      type and reference strains of bifidobacteria of 11 species. The discrimination
      power of 914bp amplicon digestion was higher than that of 523bp amplicon
      digestion. The 914bp amplicon digestion by six restrictases provided unique
      patterns for nine species; B. catenulatum and B. pseudocatenulatum were not
      differentiated yet. The NciI digestion of the 914bp PCR product enabled to
      discriminate between each of B. animalis, B. lactis, and B. gallicum. The
      reference strain B. adolescentis CCM 3761 was reclassified as a member of the B.
      catenulatum/B. pseudocatenulatum group. The above-mentioned methods were applied
      for the identification of seven strains of Bifidobacterium spp. collected in the
      Culture Collection of Dairy Microorganisms (CCDM). The strains collected in CCDM
      were differentiated to the species level. Six strains were identified as B.
      lactis, one strain as B. adolescentis.

PMID- 16423653
TI  - Kribbella yunnanensis sp. nov., Kribbella alba sp. nov., two novel species of
      genus Kribbella isolated from soils in Yunnan, China.
AB  - Two actinomycete strains, designated YIM 30006(T) and YIM 31075(T), were isolated
      from soil samples in Yunnan, China and subjected to a polyphasic taxonomic study.
      Morphological and chemotaxonomic analysis revealed that the two isolates should
      be consistent with the nocardioform actinomycetes. Comparative 16S rDNA sequences
      confirmed that the two unknown isolates to be members of the genus Kribbella.
      Based on the results of phenotypic characteristics, phylogenetic studies and DNA
      DNA hybridization results, strains YIM 30006(T) and YIM 31075(T) should be
      classified as two novel species of the genus Kribbella, for which the names
      Kribbella yunnanensis sp. nov. and Kribbella alba sp. nov. are proposed. The type
      strains for them are YIM 30006(T) (=CCTCC AA001019(T)=DSM 15499(T)) and YIM
      31075(T) (=CCTCC AA 001020(T)=DSM 15500(T)), respectively. The 16S rDNA sequences
      of strains YIM 30006(T), YIM 31075(T) have been deposited in GenBank under the
      accession numbers AY 082061 and AY 082062, respectively.

PMID- 16423655
TI  - Detection of Chromobacterium violaceum by multiplex PCR targeting the prgI, spaO,
      invG, and sipB genes.
AB  - Based on the recently completed genomic sequence of Chromobacterium violaceum
      American Type Culture Collection (ATCC) 12472 a multiplex PCR assay targeting the
      prgI, spaO, invG, and sipB genes of the Salmonella SPI-1 homologue type-III
      secretion system was developed. PCR products of 255bp (prgI), 749bp (spaO),
      1685bp (invG), and 1752bp (sipB) were successfully amplified simultaneously in a
      single reaction with all Chr. violaceum strains investigated whereas other
      bacteria tested negative. The detection limit for pure cultures in multiplex PCR
      analysis was 100CFU. The developed assay significantly improves rapid
      identification of Chr. violaceum and allows its differentiation from closely
      related organisms.

PMID- 16423656
TI  - Monitoring Lactobacillus plantarum in grass silages with the aid of 16S rDNA
      based quantitative real-time PCR assays.
AB  - Ensiling plant material with the aid of lactic acid bacteria (LAB) is a common
      agricultural practice for conserving forages independently of the time point of
      harvest. Despite ensiling being a natural process, it can be improved by the
      treatment of the harvested forage with starter cultures before storage. Within
      this context, Lactobacillus plantarum (L. plantarum) is the most frequently used
      LAB in commercially available starter cultures. In order to enable the monitoring
      of the population dynamics of L. plantarum in silage, methods for species
      specific detection based on the 16S ribosomal DNA (rDNA) sequence were developed
      by applying a quantitative real-time polymerase chain reaction (QRT-PCR)
      approach. The QRT-PCR assay was also applied to estimate the development of the
      L. plantarum population within experimental grass silages. In addition, a
      multiplex QRT-PCR assay was developed to estimate the amount of L. plantarum 16S
      rDNA in relation to total bacterial 16S rDNA. This multiplex QRT-PCR assay was
      applied to monitor the influence of different silage additives on the L.
      plantarum population.

PMID- 16423657
TI  - Polyphasic characterization of the lactic acid bacteria in kefir.
AB  - The lactic acid bacteria of kefir were isolated and characterized using
      phenotypical, biochemical, and genotypical methods. Polyphasic analyses of
      results permitted the identification of the microflora to the strain level. The
      genus Lactobacillus was represented by the species Lb. kefir and Lb.
      kefiranofaciens. Both subspecies of Lactococcus lactis (lactis and cremoris) were
      isolated. Leuconostoc mesenteroides subsp. cremoris was also found. The kefir
      studied contained few species of lactic acid bacteria but showed a high number of
      different strains. We found that the polyphasic analysis approach increases the
      confidence in strain determination. It helped confirm strain groupings and it
      showed that it could have an impact on the phylogeny of the strains.

PMID- 16423658
TI  - Oral cavity as natural reservoir for intestinal lactobacilli.
AB  - Ecological studies indicate that most Lactobacillus species found in the human
      gastrointestinal tract are likely to be transient (allochthonous), originating
      from either the oral cavity or food. In order to investigate if oral lactobacilli
      constitute a part of the faecal Lactobacillus biota, the Lactobacillus biota of
      saliva and faeces of three human subjects were investigated and compared at two
      time-points in a 3-months interval. Bacteriological culture, performed by
      incubation under standard (37 degrees C, anaerobic) and alternative (30 degrees
      C, microaerobic) conditions, as well as PCR-DGGE with group-specific primers were
      used to characterize the predominant lactobacilli. Cell counts varied among the
      subjects and over time, reaching up to 10(7)CFU/ml in saliva and 5 x 10(6)CFU/g
      in faecal samples. The species composition of the Lactobacillus biota of human
      saliva and faeces was found to be subject-specific and fluctuated to some degree,
      but the species Lactobacillus gasseri, Lactobacillus paracasei, Lactobacillus
      rhamnosus and Lactobacillus vaginalis were detected at both time-points in saliva
      and faecal samples of individual subjects. RAPD-PCR analysis indicated that
      several strains of these species were present both in the oral cavity and in the
      faecal samples of the same subject. Oral isolates of the species L. gasseri and
      L. vaginalis showing identical RAPD types were found to persist over time,
      suggesting that these species are autochthonous to the oral cavity. Our results
      together with recent published data give strong evidence that some lactobacilli
      found in human faeces are allochthonous to the intestine and originate from the
      oral cavity.

PMID- 16423659
TI  - PCR-based DGGE fingerprinting and identification of methanogens detected in three
      different types of UASB granules.
AB  - Methane is produced by various methanogenic bacteria present in upflow anaerobic
      sludge blanket (UASB) bioreactors. Methane can be used to predict and improve
      UASB bioreactor efficiency. The methanogen population in the granules can be
      influenced by the composition of the substrate. The aim of this study was to
      fingerprint and identify the methanogens present in three different types of UASB
      granules that had been used to treat winery, brewery and peach-lye canning
      effluents. This was done using polymerase chain reaction (PCR)-based denaturing
      gradient gel electrophoresis (DGGE) and DNA sequence analysis. The DGGE
      fingerprints obtained from the methanogen reference cultures of Methanosaeta
      concilii, Methanosaeta thermophila, Methanosarcina barkeri, Methanosarcina mazeii
      and Methanobacterium formicicum were compared to the DGGE profiles of the Archaea
      in the different granules. The positions of the DGGE bands that did not
      correspond well to the bands of the known species were sequenced and compared to
      sequences available on GenBank using the Blastn search option. The aligned DNA
      sequences were used to construct a phylogenetic tree. Based on the data obtained,
      a DGGE marker was constructed which was used to provide a quick method to
      identify the Archaeal members of the microbial consortium in UASB granules.

PMID- 16423662
TI  - Real-time transthoracic three-dimensional echocardiographic assessment of left
      ventricular volume and ejection fraction in congenital heart disease.
AB  - OBJECTIVE: The purpose of this study was to assess the (1) feasibility of real
      time three-dimensional echocardiography (RT-3DE) data acquisition and (2) volumes
      and function of the abnormal left ventricle (LV) in adult patients with
      congenital heart disease (CHD), compared with magnetic resonance imaging (MRI)
      data. METHODS: Thirty-two patients (59% were male) with CHD were evaluated on the
      same day by MRI and RT-3DE. Acquisition of RT-3DE data sets was feasible in 29 of
      the 32 patients (91%). The time of 3D data acquisition was 4 +/- 2 minutes, and
      LV analysis was 17 +/- 5 minutes per patient for manual border tracing. RESULTS:
      A good correlation was observed between RT-3DE with manual border detection and
      MRI for LV end-diastolic volume (r = 0.97), LV end-systolic volume (r = 0.98),
      and LV ejection fraction (r = 0.94). CONCLUSION: RT-3DE is feasible for
      volumetric analysis of the abnormal LV allowing accurate determination of LV
      volume and ejection fraction compared with MRI in adult patients with CHD.

PMID- 16423663
TI  - Feasibility and accuracy of real-time 3-dimensional echocardiographic assessment
      of ventricular septal defects.
AB  - The aim of this study was to evaluate feasibility, accuracy, and clinical
      applicability of real-time (RT) transthoracic 3-dimensional (3D) echocardiography
      (3DE) in the determination of the position, size, and shape of a ventricular
      septal defect (VSD). In all, 34 patients (age: 2 months-46 years), who were
      scheduled for surgical closure of a VSD, were enrolled in the study. VSD
      localization, shape, and dimensions were assessed and compared with measurements
      performed by the surgeon. Acquisition of RT-3DE datasets was feasible in 30 of 34
      (88%) patients. Duration of 3D data acquisition was 6 +/- 2 minutes.
      Reconstruction time was 23 +/- 16 minutes. Localization and number of VSD were
      determined correctly by RT-3DE in all patients. There was a good correlation for
      VSD measurements between RT-3DE and operation (r = 0.95). RT-3DE allows accurate
      determination of VSD size, shape, and location. The short acquisition time and
      acceptable reconstruction time make this technique clinically applicable.

PMID- 16423664
TI  - Doppler tissue, strain, and strain rate imaging in pediatric patients with
      Alstrom syndrome: are there regional functional abnormalities?
AB  - OBJECTIVE: We sought to determine the potential additive usefulness of Doppler
      tissue imaging (DTI), strain (epsilon), and epsilon rate (SR) imaging in
      assessing systolic function in pediatric patients with Alstrom syndrome. METHODS:
      We conducted a case-control study at a pediatric hospital with 5 patients (age 5
      18 years) with Alstrom syndrome living in Atlantic Canada and 21 age- and sex
      matched healthy control subjects. Standard echocardiographic examination was
      followed by DTI of the interventricular septum (IVS) and left ventricle (LV)
      lateral wall, longitudinal epsilon, and SR at the basal, mid, and apical segments
      of the LV lateral, inferior, and anterior walls, and the IVS. We also imaged
      radial epsilon and SR of the interventricular posterior wall. RESULTS: For
      patients versus control subjects, conventional ejection fraction (0.65 vs 0.72)
      and fractional shortening (0.30 vs 0.35) did not distinguish between groups. DTI
      derived s-waves consistently demonstrated significant differences in systolic
      function (LV lateral wall 0.073 vs 0.100; IVS 0.064 vs 0.080; LV anterior wall
      0.066 vs 0.096; LV inferior wall 0.069 vs 0.092 [P < .05 in all positions]).
      Epsilon differences were observed in the movement of the mid-LV lateral (-10.4 vs
      -15.2, P = .035), basal LV anterior wall (-16.3 vs -22.9, P = .004), and the
      apical IVS (-6.3 vs -13.8, P = .015). SR at the midposition of the LV lateral
      wall (-0.7 vs -1.4, P = .000) also differed between the groups. Substantial
      diastolic function differences were also observed between patients and control
      subjects. CONCLUSION: Detection of systolic and diastolic function abnormalities
      in patients with Alstrom syndrome can potentially be enhanced by the use of DTI,
      epsilon, and SR imaging.

PMID- 16423666
TI  - Risk assessment in patients with depressed left ventricular function after
      myocardial infarction using the myocardial performance index--Survival and
      Ventricular Enlargement (SAVE) experience.
AB  - BACKGROUND: Myocardial performance index (MPI) is a noninvasive, quantitative
      Doppler measure of global cardiac function, integrating systolic and diastolic
      functions. The prognostic significance of MPI is less clear for cardiovascular
      (CV) events after myocardial infarction (MI) among individuals at high risk with
      depressed left ventricular (LV) systolic function. METHODS: We analyzed
      echocardiograms from 512 patients with depressed LV function after MI enrolled in
      the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy.
      Baseline MPI measures were obtainable in 226 patients. The cohort was separated
      by median MPI (0.50). MPI was related to baseline clinical and echocardiographic
      characteristics, ventricular remodeling, and subsequent CV events, including
      recurrent MI, heart failure, CV death, and a composite of all CV end points.
      RESULTS: An MPI of 0.5 or more was associated with larger infarct size and
      reduced LV systolic function at baseline; other baseline characteristics between
      the groups were similar. A total of 64 (28.3%) patients experienced CV events.
      Baseline MPI did not influence ventricular remodeling and did not modify the
      relationship between ventricular dilatation and CV events. After covariate
      adjustment, an MPI of 0.50 or higher remained an independent predictor for
      adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43).
      CONCLUSIONS: An MPI of 0.50 or greater is an independent predictor for CV events
      after MI in patients with known LV dysfunction.

PMID- 16423665
TI  - Use of myocardial performance index in pediatric patients with idiopathic
      pulmonary arterial hypertension.
AB  - BACKGROUND: The myocardial performance index (MPI) correlates with clinical
      status in adults with idiopathic pulmonary arterial (PA) hypertension (IPAH).
      This pediatric study used MPI to assess response to bosentan therapy. METHODS:
      The study included 12 children with IPAH and 12 healthy control subjects. MPI was
      correlated with catheterization data at initiation of bosentan and at a median
      follow-up of 9 months. Therapy responders were defined by a greater than 20%
      decrease in mean PA pressure. RESULTS: Right ventricular MPI for patients with
      IPAH was 0.64 +/- 0.30 versus 0.28 +/- 0.03 in control subjects (P < .01). It had
      a strong correlation with mean PA pressure (R = 0.94; P < .001). Right
      ventricular MPI decreased significantly in responders (range 20%-44%, mean 25%)
      with a 5% increase in nonresponders. CONCLUSIONS: Right ventricular MPI in
      pediatric IPAH correlates with mean PA pressure and response to therapy. This
      study suggests that this noninvasive Doppler index may be useful to follow up
      children with IPAH, particularly when tricuspid regurgitation data are
      insufficient.

PMID- 16423667
TI  - Myocardial strain decreases with increasing transmurality of infarction: a
      Doppler echocardiographic and magnetic resonance correlation study.
AB  - BACKGROUND: Regional abnormalities in myocardial systolic function can be
      detected with myocardial strain measurements derived from Doppler tissue
      echocardiography. We studied longitudinal strain measurements in patients with
      evidence of myocardial infarction by cardiac magnetic resonance imaging to
      determine whether end-systolic strain could identify the severity of the
      infarction. METHODS: A total of 20 patients with chronic myocardial infarctions
      and 10 healthy volunteers underwent 2-dimensional echocardiography and cardiac
      magnetic resonance with delayed gadolinium (Gd) gadopentetate dimeglumine (DTPA)
      contrast hyperenhancement. Delayed Gd hyperenhancement was graded using the
      following scale: 0 = none, 1 = less than 25%, 2 = 26% to 50%, 3 = 51% to 75%, and
      4 = greater than 75%. RESULTS: There was a progressive decrease in peak systolic
      strain in the infarct segments as the transmural extent of infarction increased.
      When compared with the peak systolic strain in remote segments without evidence
      of infarction (-19.7 +/- 0.9), the strain was significantly lower in segments
      with greater than 25% Gd hyperenhancement (grade 2, -14.8 +/- 1.1, P = .001;
      grade 3, -12.9 +/- 2.1, P = .001; grade 4, -9.1 +/- 2.0, P < .001). CONCLUSIONS:
      In patients with chronic myocardial infarctions, strain measurements with
      echocardiography show a graded response of decreasing regional strain in segments
      with increasing transmural extent of infarction defined by Gd hyperenhancement.

PMID- 16423668
TI  - Effects of ultrasound contrast during tissue velocity imaging on regional left
      ventricular velocity, strain, and strain rate measurements.
AB  - BACKGROUND: Strain (epsilon) rate (SR) imaging and left ventricular (LV)
      opacification with intravenous (IV) contrast both potentially decrease operator
      dependency in interpretation of stress echocardiography. The aim of this study
      was to evaluate whether contrast present during tissue velocity imaging (TVI)
      significantly affected measurements of velocity, epsilon, and SR. Secondly, we
      sought to evaluate whether increased scan line density improved feasibility of
      simultaneous TVI and contrast echocardiography. METHODS: The 4-chamber LV view in
      15 healthy volunteers and 25 patients was acquired at rest before and after IV
      injections of contrast using: (1) conventional TVI; (2) LV opacification with
      standard TVI added; and (3) modified LV opacification with doubled TVI line
      density. Velocity, SR, and epsilon curves, along with peak systolic velocity,
      peak systolic SR, and end-systolic epsilon, were assessed from midwall segments.
      RESULTS: IV contrast significantly reduced feasibility of TVI with standard
      settings, giving noisy data for SR and epsilon, particularly in the septum.
      Absolute values of peak systolic SR and end-systolic epsilon from adequately
      shaped curves were significantly higher with contrast compared with baseline.
      However, increased TVI line density significantly improved feasibility of
      velocity traces with contrast and decreased the level of noise in SR and epsilon.
      Furthermore, higher line density improved agreement between peak systolic
      velocity, peak systolic SR, and end-systolic epsilon measured with contrast, and
      corresponding precontrast values from the conventional TVI setting. CONCLUSIONS:
      SR imaging was not feasible performed with IV contrast during conventional TVI
      settings, and we do not recommend the clinical use of this combination. Increased
      TVI line density made velocity curves with contrast feasible and resulted in less
      noisy SR and epsilon curves, but variability in SR and epsilon measurements with
      contrast is still too high for clinical use.

PMID- 16423669
TI  - Color encoding of endocardial motion improves the interpretation of contrast
      enhanced echocardiographic stress tests by less-experienced readers.
AB  - BACKGROUND: We hypothesized that color encoding of endocardial motion could aid
      less-experienced readers in detection of wall-motion abnormalities at rest and
      stress in patients with poor acoustic windows. METHODS: Color-encoded images
      (color kinesis) were obtained at rest and peak dobutamine stress in 4 standard
      views during intravenous infusion of contrast agent in 117 patients with poorly
      visualized endocardium. In 101 of 117 patients (86%), in whom contrast
      enhancement allowed endocardial tracking, images were reviewed by two expert
      readers without color overlays. Each reader graded regional wall motion as
      normal, abnormal, or uninterpretable, and their consensus grades served as a gold
      standard. The same images were then reviewed and graded with and without color
      overlays by 3 cardiology fellows. The accuracy of the interpretation was
      calculated against the gold standard separately for the 3 vascular territories
      (left anterior descending, left circumflex, and right coronary arteries) and
      averaged for the 3 fellows. RESULTS: With the addition of color encoding: (1) the
      number of uninterpretable segments decreased by 55% at rest and 61% at peak
      stress; and (2) all 3 fellows reached higher levels of accuracy in all 3 vascular
      territories both at rest (6%-82% average) and at stress (73%-80%). CONCLUSION:
      The addition of color encoding of wall motion to contrast-enhanced images
      obtained in patients with poor acoustic windows during stress tests improves the
      interpretation of regional left ventricular function by less-experienced readers.

PMID- 16423670
TI  - Heterogeneity of myocardial perfusion in distal coronary embolism with different
      particle sizes.
AB  - BACKGROUND: We hypothesized that altered myocardial perfusion distribution
      patterns could be seen with coronary distal emboli of different particle sizes
      using myocardial contrast echocardiography. METHODS: In 16 open-chest
      anesthetized dogs, microsphere suspensions of 9 or 500 microm in diameter were
      injected into the left anterior descending coronary artery until the mean left
      anterior descending coronary artery flow rate was reduced to less than 30% of
      baseline flow. During baseline conditions and after maximal embolization, real
      time myocardial contrast echocardiography was performed by intravenous infusion
      of an echocontrast agent. RESULTS: In animals infused with 9-microm microspheres,
      a transmural perfusion defect was seen at the time of maximal embolization. In
      contrast, in animals infused with 500-microm microspheres, a subendocardial
      perfusion defect was observed. CONCLUSIONS: The particle size of coronary distal
      emboli affects myocardial perfusion distribution.

PMID- 16423671
TI  - Myocardial contrast echocardiographic estimates of infarct size predict
      likelihood of left ventricular remodeling after acute anterior wall myocardial
      infarction.
AB  - OBJECTIVES: We sought to determine the utility of myocardial contrast
      echocardiography (MCE) in predicting left ventricular (LV) remodeling (LVR) in
      patients with a recent anterior wall myocardial infarction and residual regional
      LV akinesis. BACKGROUND: Although recent studies have shown that MCE predicts
      recovery of regional and global LV systolic function after myocardial infarction,
      the relationship between myocardial perfusion patterns and likelihood of
      subsequent LVR has not been extensively studied. METHODS: In all, 50 patients
      (mean age 62 years) underwent contrast-enhanced echocardiography for
      determination of LV volumes and ejection fraction, and MCE, 2 days after
      admission, with follow-up contrast-enhanced echocardiography 6 months later. LVR
      was defined as greater than 15% increase in LV end-diastolic volume index at
      follow-up. RESULTS: LVR occurred in 19 patients (38%) (group 1), with stable LV
      volumes in 31 patients (62%) (group 2). Routine clinical and angiographic
      variables did not differ between groups 1 and 2. Both transmural extent of
      infarction and number of abnormally perfused myocardial segments (assessed by
      MCE) predicted LVR. LVR occurred in 55% of patients with transmural perfusion
      defects, and was less common in those with subendocardial perfusion defects or
      normal perfusion (31% and 21%, respectively). The mean percent increase in LV
      size was significantly greater for transmural infarcts (15 +/- 7%) versus
      subendocardial infarcts or normal perfusion (-1 +/- 8 and 8 +/- 8, respectively).
      When more than 5 myocardial segments were abnormally perfused, remodeling always
      occurred and was extensive. CONCLUSIONS: MCE markers of infarct size are useful
      in predicting subsequent risk of LVR after myocardial infarction. Routine
      performance of MCE studies in select patients early after infarction may be
      helpful in further refining risk stratification.

PMID- 16423672
TI  - Geometric differences of the mitral valve tenting between anterior and inferior
      myocardial infarction with significant ischemic mitral regurgitation:
      quantitation by novel software system with transthoracic real-time three
      dimensional echocardiography.
AB  - We sought to investigate the 3-dimensional geometric differences of mitral
      leaflet tenting in ischemic mitral regurgitation, comparing inferior and anterior
      myocardial infarction (MI). Using real-time 3-dimensional echocardiography, we
      obtained transthoracic volumetric images for patients with significant ischemic
      mitral regurgitation (9 inferior and 7 anterior). With our novel software system,
      3-dimensional images of the leaflets were reconstructed for quantitation. Mitral
      leaflet configuration was then represented in contour in which the degree of the
      tenting could be observed. Calculated percent of tethered leaflet area (>5-mm
      tenting from the annular level) was compared in inferior and anterior MI. Percent
      of tethered leaflet area was significantly smaller in inferior than anterior MI,
      reflecting the localized leaflet tenting in inferior MI (16.7 +/- 18.8% vs 38.9
      +/- 9.7%, P = .01). In anterior MI, mitral valve leaflets were widely tethered
      toward the left ventricle, in contrast with inferior MI showing localized tenting
      of the leaflet.

PMID- 16423673
TI  - Relationship of mitral annular remodeling to severity of chronic mitral
      regurgitation.
AB  - HYPOTHESES: (1) Mitral regurgitation (MR) severity is directly associated with
      mitral annular remodeling as evidenced by mitral annular enlargement. (2)
      Increasing severity of chronic MR will result in symmetric enlargement of the
      mitral annulus as measured by annular shape indices. BACKGROUND: Limited data
      exist on mitral annular remodeling for patients with MR. Identification of
      annular changes may be important in aiding surgical repair. METHODS: The mitral
      annulus was measured in several planes using transthoracic echocardiography in
      173 patients: trace to no MR (34), mild MR (48), moderate MR (45), and severe MR
      (46). Patients were subgrouped by mechanism of MR and annular shape indices were
      determined. RESULTS: With increasing MR severity, there was a corresponding
      symmetric increase in all systolic and diastolic measurements, but no significant
      differences in annular shape indices between subgroups by MR severity or by MR
      mechanism. CONCLUSIONS: Mitral annular remodeling is symmetric, regardless of
      degree or mechanism of MR.

PMID- 16423674
TI  - Early mitral filling/diastolic mitral annular velocity ratio is not a reliable
      predictor of left ventricular filling pressure in the setting of severe mitral
      regurgitation.
AB  - The early mitral filling velocity (E)/early diastolic mitral annular velocity
      (E') ratio is increasingly being used as a simplified approach to estimate left
      ventricular (LV) filling pressure. The validity of applying this Doppler
      parameter to patients with severe mitral regurgitation is unknown. We
      retrospectively identified 20 patients in sinus rhythm who had LV end-diastolic
      pressure (LVEDP) invasively measured within 72 hours of a full echocardiogram
      including diastolic parameters. We observed a poor correlation between E/E' ratio
      and LVEDP in these patients (r = -0.07, P = not significant). Previously
      described E/E' cut-off values did not accurately identify patients with low,
      intermediate, and high LVEDP. Of the diastolic parameters measured, the most
      significant correlation with LVEDP was found with mitral deceleration time (r = 
      0.66, P = .002) and systolic/diastolic peak velocity ratio (r = -0.52, P = .02).
      We conclude that E/E' ratio is not reliable in predicting LV filling pressure in
      the setting of severe mitral regurgitation, and that in these cases mitral
      deceleration time or systolic/diastolic peak velocity ratio may be better
      indicators of LVEDP.

PMID- 16423675
TI  - Mitral annulus motion as a predictor of mortality in a community-based sample of
      75-year-old men and women.
AB  - Mitral annulus motion (MAM) is a predictor of mortality in selected patient
      groups, but its prognostic value in less selected populations is not known. In a
      community-based random sample of 75-year-old men and women (n = 408), left
      ventricular function was measured as: (1) maximum amplitude of MAM; and (2) wall
      motion index. During a median follow-up of 7.2 years, 83 persons died (26 from
      cardiac causes). Left ventricular function as measured by MAM predicted the risk
      of all-cause and cardiac mortality independently of other potential risk factors
      in this community-based sample. Regarding cardiac mortality, the predictive
      ability of MAM was also independent of left ventricular systolic function
      measured as wall-motion index. MAM may prove to be a valuable complement to other
      echocardiographic methods in the assessment of prognosis in less selected
      populations.

PMID- 16423676
TI  - Left bundle branch block in chronic heart failure-impact on diastolic function,
      filling pressures, and B-type natriuretic peptide levels.
AB  - BACKGROUND: For patients with chronic heart failure (CHF), left bundle branch
      block (LBBB) is associated with impaired systolic function and increased
      morbidity and mortality, but data on diastolic function are scarce. In this
      patient population, we attempted to define the impact of LBBB on diastolic
      function, filling pressures, and brain natriuretic peptide and its circulating N
      terminal precursor (NT-proBNP) levels. METHODS: A total of 94 patients with
      stable CHF (48 with complete LBBB, 46 without intraventricular conduction delay
      and normal QRS duration) underwent conventional 2-dimensional/Doppler
      echocardiography and Doppler tissue analysis of mitral annular velocities. As a
      measure of left ventricular filling pressures, the ratio of peak early mitral
      flow velocity to peak early diastolic mitral annular velocity was derived. NT
      proBNP measurements were carried out on a bench-top analyzer (Elecsys-2010, Roche
      Diagnostics, Mannheim, Germany). RESULTS: Patients with or without LBBB did not
      differ with respect to the cause of CHF or ejection fraction, but in LBBB
      deceleration time was shorter (163 +/- 66 vs 205 +/- 95 milliseconds, P = .021)
      and a restrictive mitral filling pattern was more frequent (35% vs 11%, P =
      .005). In such patients, the ratio of peak early mitral flow velocity to peak
      early diastolic mitral annular velocity was higher (14.5 +/- 6.2 vs 10.6 +/- 5.2,
      P < .001) and NT-proBNP was elevated (3553 +/- 3725 vs 850 +/- 896 pg/mL, P <
      .01) as compared with patients without LBBB. CONCLUSION: For patients with CHF
      and comparable systolic performance, LBBB is associated with more severe
      diastolic dysfunction, elevated filling pressures, and higher NT-proBNP levels.
      These findings may contribute to increased morbidity and mortality of such
      patients.

PMID- 16423677
TI  - Hemodynamic significance of mitral stenosis: use of a simple, novel index by 2
      dimensional echocardiography.
AB  - OBJECTIVE: We sought to assess the hemodynamic significance of mitral stenosis
      (MS) using a new index. METHODS: We studied 88 patients with MS. Maximum
      separation of mitral leaflet tips in diastole in parasternal long-axis and apical
      4-chamber views was measured. These two parameters were averaged to yield the
      mitral leaflet separation index. The index was compared with mitral valve area by
      planimetry and pressure half-time. RESULTS: The mitral leaflet separation index
      was measurable in 76 (86.4%) patients. There was excellent correlation with
      mitral valve area by planimetry (r = 0.91, P < .001) and pressure half-time (r =
      0.86, P < .001) across a wide range of mitral valve areas. Good correlation was
      found even in atrial fibrillation (r = 0.86 and r = 0.79, respectively). The
      index could discriminate between hemodynamically significant and insignificant MS
      (P < .001). An index of 0.81 cm or less predicted severe MS with 92.3%
      sensitivity and 100% specificity whereas a value of 1.11 cm or more identified
      mild MS with 85.7% sensitivity and 100% specificity. CONCLUSION: The mitral
      leaflet separation index is an independent and reliable measure of MS severity
      that is easy to measure.

PMID- 16423678
TI  - Primary large B-cell cardiac lymphoma.
AB  - Primary cardiac lymphomas are rare. They can be detected incidentally during
      echocardiography or cardiac operation. They can have various clinical
      manifestations. We report a case of primary cardiac large B-cell lymphoma in a 66
      year-old man with symptoms of chest pain and light-headedness who was found to
      have a right atrial mass with echocardiography and without right ventricular
      outflow tract obstruction or pericardial involvement.

PMID- 16423679
TI  - "Steal" collaterals: an echocardiographic diagnostic marker for anomalous origin
      of the left main coronary artery from the pulmonary artery in the adult.
AB  - Anomalous origin of the left main coronary artery from the pulmonary artery, also
      known as Bland-White-Garland syndrome, is a rare malformation. Few patients
      survive past childhood without surgical repair, and up to 90% die suddenly at a
      mean age of 35 years. We describe a case of a 60-year-old patient with anomalous
      origin of the left main coronary artery from the pulmonary artery in which 2
      dimensional and color flow Doppler visualization of the intercoronary (so-called
      "steal") collaterals was the first marker that alerted the examiner to the
      possibility of this diagnosis, subsequently guided step-by-step the
      echocardiographic approach.

PMID- 16423680
TI  - Real-time 3-dimensional echocardiographic evaluation of aortic dissection.
AB  - Prompt and correct diagnosis is the cornerstone of effective treatment of aortic
      (Ao) dissection. Recent studies have demonstrated the usefulness of newly
      developed imaging modalities for diagnosis of Ao dissection (digital subtraction
      arteriography, computed tomography, magnetic resonance imaging, and
      transoesophageal echocardiography). The aim of this study was to demonstrate the
      clinical usefulness of real-time 3-dimensional echocardiography for the spatial
      assessment of the Ao tract. Our case suggested that real-time 3-dimensional
      echocardiography is a valuable method for real-time noninvasive spatial
      evaluation of dissection of the Ao tract.

PMID- 16423681
TI  - Hypertrabeculation is not distinct from noncompaction in neuromuscular and
      nonneuromuscular disorders.

PMID- 16423682
TI  - Asynchrony detection and Doppler tissue imaging.

PMID- 16423683
TI  - Killed in action: microbiologists and clinicians as victims of their occupation.
      Part 4: Tick-borne Relapsing Fever, Malta Fever, Glanders, SARS.

PMID- 16423684
TI  - Phage therapy: facts and fiction.
AB  - Recent examples of the use of bacteriophages in controlling bacterial infections
      are presented, some of which show therapeutic promise. The therapeutic use of
      bacteriophages, possibly in combination with antibiotics, may be a valuable
      approach. However, it is also quite clear that the safe and controlled use of
      phage therapy will require detailed information on the properties and behavior of
      specific phage-bacterium systems, both in vitro and especially in vivo. In vivo
      susceptibility of bacterial pathogens to bacteriophages is still largely poorly
      understood and future research on more phage-bacterium systems has to be
      undertaken to define the requirements for successful phage treatments.

PMID- 16423685
TI  - The Legionella pneumophila global regulatory protein LetA affects DotA and Mip.
AB  - Several genes have been identified in Legionella pneumophila which are necessary
      for its virulence properties. These genes include the dot/icm type IV secretion
      system (T4SS), mip and letA. Genes of the dot/icm system, in particular dotA,
      have been found to be essential for intracellular growth. The macrophage
      infectivity protein (Mip) is also necessary for full virulence of the bacteria.
      Although these genes are well characterized, the regulation of such virulence
      factors is not. The LetA transcriptional activator interacts with the global
      regulator CsrA in controlling the switch from the replicative, non-infectious to
      the transmissive, highly infectious form of L. pneumophila. Regulation by LetA of
      the dot/icm genes has also been previously postulated. Here we show that the letA
      mutation exerts effects not only on DotA but on a substrate of the secretion
      system, RalF as well. LetA was found to be necessary for full transcriptional
      expression of the dotA and ralF genes. Although at the transcriptional level dotA
      was reduced, this did not result in a decrease of DotA protein in whole cell
      lysates. The letA mutation, however, does result in decreased amounts of the DotA
      protein found in the membrane and increased amounts in the culture supernatant.
      Additionally, the letA mutation dramatically decreased the secretion of Mip. This
      work demonstrates the participation of the global regulatory protein LetA in the
      regulation of an essential part of the dot/icm T4SS. Also shown is the presence
      of secreted Mip and a decrease in this secretion in the letA(-) strain. Exactly
      how LetA is regulating these virulence factors remains to be elucidated but it
      obviously occurs at both transcriptional and post-transcriptional levels.

PMID- 16423686
TI  - Detection of cdtA, cdtB, and cdtC genes in Campylobacter jejuni by multiplex PCR.
AB  - A multiplex PCR was developed for simultaneous detection of the cytolethal
      distending toxin (cdt) genes of Campylobacter jejuni. Three primer pairs
      targeting each one of the cdtA, cdtB and cdtC genes were designed and combined in
      the same PCR reaction. The assay was evaluated with 100 C. jejuni strains
      recovered from humans and animals and it was found to be rapid and specific. Two
      isolates presented several deletions affecting both cdtA and cdtB genes. High
      prevalence (98%) of the three cdt genes was found among isolates of different
      geographic origins.

PMID- 16423687
TI  - Genotypic characterization of toxic shock syndrome toxin-1-producing strains of
      Staphylococcus aureus isolated in the Czech Republic.
AB  - Genotyping based on pulsed-field gel electrophoresis (PFGE), PCR ribotyping,
      enterobacterial repetitive intergenic consensus motif (ERIC2)-PCR, and prophage
      content analysis was carried out in 45 toxic shock syndrome toxin-1 (TSST-1)
      positive Staphylococcus aureus strains isolated in 19 cities of the Czech
      Republic between 1986 and 2004. Twenty-four wild-type TSST-1-positive isolates of
      which 18 strains were the causative agents of toxic shock syndrome (TSS) had the
      same genotype profiles as the type strain FRI 1169 and were classified into
      genotype T1. The remaining 21 strains of which 12 caused TSS were distinct from
      one another and differed from the T1 strains mainly in PFGE pattern and also in
      one or more other genetic characteristics. While the strains of genotype T1 are
      most prevalent in the Czech population and account for the majority of TSS cases,
      TSS-related S. aureus strains of different genotypes were also found and cannot
      be excluded as the causative agents of TSS cases in this country.

PMID- 16423688
TI  - Synaptic vesicles caught kissing again.
AB  - In this issue of Neuron, Harata et al. use a novel quenching technique to provide
      compelling evidence that kiss-and-run is the dominant mode of vesicle fusion at
      hippocampal synapses and that the prevalence of kiss-and-run can be modulated by
      stimulus frequency. The increased incidence of kiss-and-run at lower frequencies
      may ensure that vesicles are available for use during periods of high demand.

PMID- 16423689
TI  - Flick-induced flips in perception.
AB  - Microsaccades are miniature eye movements produced involuntarily during visual
      fixation of stationary objects. Since their first description more than 40 years
      ago, the role of microsaccades in vision has been controversial. In this issue,
      Martinez-Conde and colleagues present a solution to the long-standing research
      problem connecting this basic oculomotor function to visual perception, by
      showing that microsaccades may control peripheral vision during visual fixation
      by inducing flips in bistable peripheral percepts in head-unrestrained viewing.
      Their study provides new insight into the functional connectivity between
      oculomotor function and visual perception.

PMID- 16423690
TI  - Selectivity of adaptation in single units: implications for FMRI experiments.
AB  - Understanding the neural basis of adaptation (repetition suppression) is critical
      for interpreting fMRI-adaptation experiments. Sawamura and colleagues provide a
      critical stepping-stone by elucidating the relation between neural adaptation and
      response selectivity. They find some cross-adaptation by two different stimuli
      that activate the same neuron.

PMID- 16423691
TI  - Watching the fly brain learn.
AB  - The peptidergic dorsal paired medial (DPM) neurons, which innervate the mushroom
      bodies in Drosophila, have been widely hypothesized to be part of the
      unconditioned stimulus (US) pathway of odor-shock classical conditioning. In the
      December 2 issue of Cell, Yu et al., using functional imaging techniques, report
      the surprising finding that DPMs contain odor-specific memory traces and send
      integrated information about the conditioned stimulus (CS) to the mushroom
      bodies. These findings provide important new insight into the circuitry of
      learning in Drosophila.

PMID- 16423692
TI  - A critical role for myosin IIb in dendritic spine morphology and synaptic
      function.
AB  - Dendritic spines show rapid motility and plastic morphology, which may mediate
      information storage in the brain. It is presently believed that
      polymerization/depolymerization of actin is the primary determinant of spine
      motility and morphogenesis. Here, we show that myosin IIB, a molecular motor that
      binds and contracts actin filaments, is essential for normal spine morphology and
      dynamics and represents a distinct biophysical pathway to control spine size and
      shape. Myosin IIB is enriched in the postsynaptic density (PSD) of neurons.
      Pharmacologic or genetic inhibition of myosin IIB alters protrusive motility of
      spines, destabilizes their classical mushroom-head morphology, and impairs
      excitatory synaptic transmission. Thus, the structure and function of spines is
      regulated by an actin-based motor in addition to the polymerization state of
      actin.

PMID- 16423693
TI  - Receptive-field modification in rat visual cortex induced by paired visual
      stimulation and single-cell spiking.
AB  - Experience-dependent plasticity of visual cortical receptive fields (RFs)
      involves synaptic modifications in the underlying neural circuits, but the site
      and mechanism of these modifications remain to be elucidated. Using in vivo whole
      cell recordings, we show that pairing visual stimulation at a given retinal
      location with spiking of a single neuron in developing rat visual cortex induces
      rapid RF modifications. The time course of the response to the visual stimulus at
      the paired RF location is altered, with an enhancement of the response preceding
      the spike time and a reduction following the spike. Such bidirectional
      modification is consistent with spike timing-dependent plasticity. Response
      modification also occurs at nearby locations, the direction and magnitude of
      which are correlated with the change at the paired location. In addition, changes
      at unpaired locations show a negative correlation with the initial strength of
      the response, which may facilitate rapid modification of the spatial RF profile.

PMID- 16423694
TI  - Leptin directly activates SF1 neurons in the VMH, and this action by leptin is
      required for normal body-weight homeostasis.
AB  - Leptin, an adipocyte-derived hormone, acts directly on the brain to control food
      intake and energy expenditure. An important question is the identity of first
      order neurons initiating leptin's anti-obesity effects. A widely held view is
      that most, if not all, of leptin's effects are mediated by neurons located in the
      arcuate nucleus of the hypothalamus. However, leptin receptors (LEPRs) are
      expressed in other sites as well, including the ventromedial hypothalamus (VMH).
      The possible role of leptin acting in "nonarcuate" sites has largely been
      ignored. In the present study, we show that leptin depolarizes and increases the
      firing rate of steroidogenic factor-1 (SF1)-positive neurons in the VMH. We also
      show, by generating mice that lack LEPRs on SF1-positive neurons, that leptin
      action at this site plays an important role in reducing body weight and, of note,
      in resisting diet-induced obesity. These results reveal a critical role for
      leptin action on VMH neurons.

PMID- 16423695
TI  - Regulation of layer-specific targeting by reciprocal expression of a cell
      adhesion molecule, capricious.
AB  - Layer-specific innervation is a major form of synaptic targeting in the central
      nervous system. In the Drosophila visual system, photoreceptors R7 and R8 connect
      to targets in distinct layers of the medulla, a ganglion of the optic lobe. We
      show here that Capricious (CAPS), a transmembrane protein with leucine-rich
      repeats (LRRs), is a layer-specific cell adhesion molecule that regulates
      photoreceptor targeting in the medulla. During the period of photoreceptor
      targeting, caps is specifically expressed in R8 and its target layer but not in
      R7 or its recipient layer. caps loss-of-function mutations cause local targeting
      errors by R8 axons, including layer change. Conversely, ectopic expression of
      caps in R7 redirects R7 axons to terminate in the CAPS-positive R8 recipient
      layer. CAPS promotes homophilic cell adhesion in transfected S2 cells. These
      results suggest that CAPS regulates layer-specific targeting by mediating
      specific axon-target interaction.

PMID- 16423696
TI  - Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth
      cones.
AB  - Slits mediate multiple axon guidance decisions, but the mechanisms underlying the
      responses of growth cones to these cues remain poorly defined. We show here that
      collapse induced by Slit2-conditioned medium (Slit2-CM) in Xenopus retinal growth
      cones requires local protein synthesis (PS) and endocytosis. Slit2-CM elicits
      rapid activation of translation regulators and MAP kinases in growth cones, and
      inhibition of MAPKs or disruption of heparan sulfate blocks Slit2-CM-induced PS
      and repulsion. Interestingly, Slit2-CM causes a fast PS-dependent decrease in
      cytoskeletal F-actin concomitant with a PS-dependent increase in the actin
      depolymerizing protein cofilin. Our findings reveal an unexpected link between
      Slit2 and cofilin in growth cones and suggest that local translation of actin
      regulatory proteins contributes to repulsion.

PMID- 16423697
TI  - Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and
      photoreceptor cell survival.
AB  - In sensory neurons, successful maturation of signaling molecules and regulation
      of Ca2+ are essential for cell function and survival. Here, we demonstrate a
      multifunctional role for calnexin as both a molecular chaperone uniquely required
      for rhodopsin maturation and a regulator of Ca2+ that enters photoreceptor cells
      during light stimulation. Mutations in Drosophila calnexin lead to severe defects
      in rhodopsin (Rh1) expression, whereas other photoreceptor cell proteins are
      expressed normally. Mutations in calnexin also impair the ability of
      photoreceptor cells to control cytosolic Ca2+ levels following activation of the
      light-sensitive TRP channels. Finally, mutations in calnexin lead to retinal
      degeneration that is enhanced by light, suggesting that calnexin's function as a
      Ca2+ buffer is important for photoreceptor cell survival. Our results illustrate
      a critical role for calnexin in Rh1 maturation and Ca2+ regulation and provide
      genetic evidence that defects in calnexin lead to retinal degeneration.

PMID- 16423698
TI  - Frequency-dependent kinetics and prevalence of kiss-and-run and reuse at
      hippocampal synapses studied with novel quenching methods.
AB  - The kinetics of exo-endocytotic recycling could restrict information transfer at
      central synapses if neurotransmission were entirely reliant on classical full
      collapse fusion. Nonclassical fusion retrieval by kiss-and-run would be
      kinetically advantageous but remains controversial. We used a hydrophilic
      quencher, bromophenol blue (BPB), to help detect nonclassical events. Upon
      stimulation, extracellular BPB entered synaptic vesicles and quenched FM1-43
      fluorescence, indicating retention of FM dye beyond first fusion. BPB also
      quenched fluorescence of VAMP (synaptobrevin-2)-EGFP, thus indicating the timing
      of first fusion of vesicles in the total recycling pool. Comparison with FM dye
      destaining revealed that kiss-and-run strongly prevailed over full-collapse
      fusion at low frequency, giving way to a near-even balance at high frequency.
      Quickening of kiss-and-run vesicle reuse was also observed at higher frequency in
      the average single vesicle fluorescence response. Kiss-and-run and reuse could
      enable hippocampal nerve terminals to conserve scarce vesicular resources when
      responding to widely varying input patterns.

PMID- 16423699
TI  - Contrasting effects of the persistent Na+ current on neuronal excitability and
      spike timing.
AB  - The persistent Na+ current, INaP, is known to amplify subthreshold oscillations
      and synaptic potentials, but its impact on action potential generation remains
      enigmatic. Using computational modeling, whole-cell recording, and dynamic clamp
      of CA1 hippocampal pyramidal cells in brain slices, we examined how INaP changes
      the transduction of excitatory current into action potentials. Model simulations
      predicted that INaP increases afterhyperpolarizations, and, although it increases
      excitability by reducing rheobase, INaP also reduces the gain in discharge
      frequency in response to depolarizing current (f/I gain). These predictions were
      experimentally confirmed by using dynamic clamp, thus circumventing the
      longstanding problem that INaP cannot be selectively blocked. Furthermore, we
      found that INaP increased firing regularity in response to sustained
      depolarization, although it decreased spike time precision in response to single
      evoked EPSPs. Finally, model simulations demonstrated that I(NaP) increased the
      relative refractory period and decreased interspike-interval variability under
      conditions resembling an active network in vivo.

PMID- 16423700
TI  - Synchronization of olfactory bulb mitral cells by precisely timed inhibitory
      inputs.
AB  - Synchronized oscillatory activity at the gamma frequency (30-70 Hz) is thought to
      be important for information processing in many sensory systems. Here, I used
      patch-clamp recordings in neuron pairs in rat olfactory bulb slices to assess the
      mechanisms underlying such "gamma" activity in the olfactory system. Patterned
      electrical stimulation of afferents that mimicked a natural odor stimulus
      elicited rapidly synchronized spikes (lag < or = 5 ms) in mitral cells, along
      with oscillatory activity at the gamma (approximately 50 Hz) frequency. Analysis
      of coupling potentials, combined with dendritic sectioning, indicated that mitral
      cell synchrony was mainly driven by inhibitory postsynaptic potentials (IPSPs)
      imposed by GABAergic granule cells. Recordings in granule cell pairs indicated
      that granule cells were themselves synchronized by their excitatory inputs from
      mitral cells, providing a means to coordinate GABA release. These results
      demonstrate that rapid synchrony can emerge in a network through the precise back
      and-forth interplay between neuronal populations.

PMID- 16423701
TI  - Imaging taste responses in the fly brain reveals a functional map of taste
      category and behavior.
AB  - The sense of taste allows animals to distinguish nutritious and toxic substances
      and elicits food acceptance or avoidance behaviors. In Drosophila, taste cells
      that contain the Gr5a receptor are necessary for acceptance behavior, and cells
      with the Gr66a receptor are necessary for avoidance. To determine the cellular
      substrates of taste behaviors, we monitored taste cell activity in vivo with the
      genetically encoded calcium indicator G-CaMP. These studies reveal that Gr5a
      cells selectively respond to sugars and Gr66a cells to bitter compounds. Flies
      are attracted to sugars and avoid bitter substances, suggesting that Gr5a cell
      activity is sufficient to mediate acceptance behavior and that Gr66a cell
      activation mediates avoidance. As a direct test of this hypothesis, we inducibly
      activated different taste neurons by expression of an exogenous ligand-gated ion
      channel and found that cellular activity is sufficient to drive taste behaviors.
      These studies demonstrate that taste cells are tuned by taste category and are
      hardwired to taste behaviors.

PMID- 16423703
TI  - Selectivity of neuronal adaptation does not match response selectivity: a single
      cell study of the FMRI adaptation paradigm.
AB  - fMRI-based adaptation paradigms (fMR-A) have been used to infer neuronal stimulus
      selectivities in humans. Inferring neuronal selectivities from fMR-A, however,
      requires an understanding of the relationship between the stimulus selectivity of
      neuronal adaptation and responses. We studied this relationship by recording
      single cells in macaque inferior temporal (IT) cortex, an area that shows fMRI
      adaptation. Repetition of identical object images reduced the responsiveness of
      single IT neurons. Presentation of an image to which the neuron was unresponsive
      did not alter the response to a subsequent image that activated the neuron.
      Successive presentation of two different images to which the neuron responded
      similarly produced adaptation, but less so than the repeated presentation of an
      image. The neuronal adaptation at the single-cell level showed a greater degree
      of stimulus selectivity than the responses. This complicates the interpretation
      of fMR-A paradigms when inferring neuronal selectivity.

PMID- 16423702
TI  - Microsaccades counteract visual fading during fixation.
AB  - Our eyes move continually, even while we fixate our gaze on an object. If
      fixational eye movements are counteracted, our perception of stationary objects
      fades completely, due to neural adaptation. Some studies have suggested that
      fixational microsaccades refresh retinal images, thereby preventing adaptation
      and fading. However, other studies disagree, and so the role of microsaccades
      remains unclear. Here, we correlate visibility during fixation to the occurrence
      of microsaccades. We asked subjects to indicate when Troxler fading of a
      peripheral target occurs, while simultaneously recording their eye movements with
      high precision. We found that before a fading period, the probability, rate, and
      magnitude of microsaccades decreased. Before transitions toward visibility, the
      probability, rate, and magnitude of microsaccades increased. These results reveal
      a direct link between suppression of microsaccades and fading and suggest a
      causal relationship between microsaccade production and target visibility during
      fixation.

PMID- 16423706
TI  - 2005 Gap Junction Conference, Whistler, British Columbia, Canada. Abstracts.

PMID- 16423710
TI  - Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in
      chronic anxiety.
AB  - Stress initiates a series of neuronal responses that prepare an organism to adapt
      to new environmental challenges. However, chronic stress may lead to maladaptive
      responses that can result in psychiatric syndromes such as anxiety and depressive
      disorders. Corticotropin-releasing factor (CRF) has been identified as a key
      neuropeptide responsible for initiating many of the endocrine, autonomic and
      behavioral responses to stress. The amygdala expresses high concentrations of CRF
      receptors and is itself a major extrahypothalamic source of CRF containing
      neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role
      in regulating anxiety and affective responses. During periods of stress, CRF is
      released into the amygdala and local CRF receptor activation has been postulated
      as a substrate for stress-induced alterations in affective behavior. Previous
      studies have suggested that synaptic plasticity in the BLA contributes to
      mechanisms underlying long-term changes in the regulation of affective behaviors.
      Several studies have shown that acute glutamate receptor-mediated activation, by
      either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term
      synaptic plasticity and increases the excitability of BLA neurons. This review
      summarizes some of the data supporting the hypotheses that stress induced
      plasticity within the amygdala may be a critical step in the pathophysiology of
      the development of chronic anxiety states. It is further proposed that such a
      change in the limbic neural circuitry is involved in the transition from normal
      vigilance responses to pathological anxiety, leading to syndromes such as panic
      and post-traumatic stress disorders.

PMID- 16423711
TI  - Cortico-amygdala circuits: role in the conditioned stress response.
AB  - The amygdala plays a crucial role in the orchestration and modulation of the
      organism response to aversive, stressful events. This response could be conceived
      as the result of two interdependent components. The first is represented by sets
      of visceral and motor responses aimed at helping the organism to cope with the
      present event. The second is the acquisition and modulation of memories relative
      to the stressful stimulus and its context. This latter component contributes to
      the instatement of conditioned stress responses that are essential to the
      capability of the organism to predict future exposures to similar stimuli in
      order to avoid them or counteract them effectively. In the amygdala, these two
      components become fully integrated. Massive networks link the amygdala to the
      hypothalamus, midbrain and brainstem. These networks convey visceral, humoral and
      nociceptive information to the amygdala and mediate its effects on the
      hypothalamic-pituitary-adrenal axis as well on autonomic and motor centers. On
      the other hand, interactions between the amygdala and interconnected cortical
      networks play a crucial role in acquisition, consolidation and extinction of
      learning relative to the stressful stimulus. Within the scope of this review,
      current evidence relative to the interaction between the amygdala and cortical
      networks will be considered in relationship to the integration of the conditioned
      response to stress.

PMID- 16423712
TI  - Modulation of anxiety circuits by serotonergic systems.
AB  - Anxiety is a complex emotional state associated with sustained heightened
      autonomic and behavioral arousal and an increase in avoidance behavior. Anxiety
      related behavior is a form of risk assessment behavior that is associated with a
      level of uncertainty or unpredictability regarding the outcome of emotionally
      salient events, often when both rewarding and aversive outcomes are possible. In
      this review, we highlight recent advances in our understanding of the neural
      circuits regulating anxiety states and anxiety-related behavior with an emphasis
      on the role of brainstem serotonergic systems in modulating anxiety-related
      circuits. In particular, we explore the possibility that the regulation of
      anxiety states and anxiety-related behavior by serotonergic systems is dependent
      on a specific, topographically organized mesolimbocortical serotonergic system
      that originates in the mid-rostrocaudal and caudal parts of the dorsal raphe
      nucleus.

PMID- 16423713
TI  - Early maternal deprivation retards neurodevelopment in Wistar rats.
AB  - A single 24 h period of maternal deprivation (MD) in rats has been shown to
      induce, in adulthood, a number of abnormalities in brain and behaviour that also
      occur in patients with schizophrenia. However, the short-term behavioural effects
      of MD have not been studied in detail. Since patients with schizophrenia are
      characterized by a retardation of normal development, we aimed in the present
      study to investigate the development of control rats and rats that were exposed
      to MD on postnatal day 9. Compared to control animals, MD rats showed (1) a
      reduction in body weight, (2) an increased in reversal latency in negative
      geotaxis, (3) a delayed eye opening, (4) a delayed emergence of walking and
      rearing; and (5) a delayed emergence of the behavioural response to amphetamine
      (amph). On the other hand, MD and control rats responded similarly to the non
      competitive NMDA antagonist MK801. These data clearly show that early MD delays
      development, especially of the dopaminergic system and confirm our hypothesis
      that MD may represent an interesting animal model for the neurodevelopmental
      hypothesis of schizophrenia.

PMID- 16423714
TI  - Social isolation-induced changes in the hypothalamic-pituitary-adrenal axis in
      the rat.
AB  - Social isolation of rats both reduces the cerebrocortical and plasma
      concentrations of 3a-hydroxy-5a-pregnan-20-one (3a,5a-TH PROG) and 3a,5a
      tetrahydrodeoxycorticosterone and potentiates the positive effects of acute
      stress and ethanol on the concentrations of these neuroactive steroids. We now
      show that social isolation decreased the plasma level of adrenocorticotropin
      (ACTH), moreover, intracerebroventricular administration of corticotropin
      releasing factor (CRF) induced a marked increase in the plasma corticosterone
      level in both isolated and group-housed rats, but this effect was significantly
      greater in the isolated rats (+121%) than in the group-housed rats (+86%). In
      addition, in isolated rats, a low dose of dexamethasone had no effect on the
      plasma corticosterone concentration, whereas, a high dose significantly reduced
      it; both doses of dexamethasone reduced plasma corticosterone in group-housed
      rats. Furthermore, the corticosterone level after injection of dexamethasone at
      the high dose was significantly greater in the isolated animals than in the group
      housed rats. These results suggest that social isolation increased sensitivity of
      the pituitary to CRF and impaired negative feedback regulation of the
      hypothalamic-pituitary-adrenal (HPA) axis.

PMID- 16423715
TI  - Stress-induced progesterone secretion and progesterone receptor immunoreactivity
      in the paraventricular nucleus are modulated by pubertal development in male
      rats.
AB  - Male rats show a differential adrenocortical response to stress before and after
      pubertal development, such that prepubertal animals have a more prolonged stress
      induced corticosterone response compared to adults. Whether pubertal maturation
      affects other adrenocortical responses to stress is currently unknown. To address
      this question, we assessed stress-induced progesterone secretion in both intact
      and gonadectomized prepubertal (28 days of age) and adult (77 days of age) male
      rats either before or after exposure to a 30 min session of restraint stress. We
      found that prepubertal males show a greater and more prolonged stress-induced
      progesterone response compared to adults. We also found a similar effect in
      castrated prepubertal and adult males, indicating the differential stress-induced
      progesterone response is not gonadal in origin. We also examined progesterone
      receptor (PR) levels by immunohistochemistry in the paraventricular nucleus (PVN)
      of the hypothalamus, a key regulatory nucleus of the hypothalamic-pituitary
      adrenal (HPA) axis, and found lower PR protein expression in the PVN of
      prepubertal compared to adult males. These data indicate that in addition to
      corticosterone, stress-induced adrenocortical progesterone levels are
      differentially affected by pubertal maturation. Furthermore, these data raise the
      possibility of different progesterone sensitivity of the PVN before and after
      puberty. The significance of this differential response is presently unknown.
      However, given the pleiotropic effects of progesterone on male physiology and
      behaviour, it is likely that the disparate post-stress exposure to progesterone
      affects the prepubertal and adult male differently.

PMID- 16423716
TI  - Enhanced involvement of brain vasopressin V1 receptors in cardiovascular
      responses to stress in rats with myocardial infarction.
AB  - Stress is one of the factors provoking cardiovascular complications. The purpose
      of the study was to explore the role of vasopressin (VP) in central control of
      arterial blood pressure and heart rate under resting conditions and during
      stimulation by an alarming stress (air jet stress) in myocardial infarct-induced
      cardiac failure. Six groups of male Sprague Dawley (SD) rats were subjected
      either to sham surgery (sham rats) or to ligation of a left coronary artery
      (infarcted rats). After 5 weeks both infarcted and sham rats were subjected
      either to intracerebroventricular infusion of artificial cerebrospinal fluid
      (aCSF) (sham aCSF and infarcted aCSF), [Arg8]-VP (sham VP and infarcted VP) or VP
      V1a receptor antagonist (d(CH2)5[Tyr(Me)2Ala-]VP, sham V1ANT and infarcted
      V1ANT). Air jet stress elicited significantly greater increases in mean arterial
      blood pressure (MABP) and heart rate in the infarcted aCSF than in the sham aCSF
      rats. Intracerebroventricular infusion of V1ANT significantly reduced resting
      MABP and MABP and heart rate increases in response to stress in the infarcted but
      not in the sham rats. Intracerebroventricular infusion of VP elicited a
      significant increase in resting MABP in the infarcted VP but not in the sham VP
      rats. The results provide evidence for enhanced engagement of the brain V1 VP
      receptors in regulation of resting MABP and in generation of exaggerated
      cardiovascular responses to air jet stress during the post-infarct state.

PMID- 16423718
TI  - Ecotoxicity of pentachlorophenol in contaminated soil as affected by soil type.
AB  - Four uncontaminated soils were chosen with a wide range of pH, organic carbon,
      and clay content to allow us to determine the properties that were most
      influential on pentachlorophenol (PCP) toxicity. The soils were contaminated in
      the laboratory at concentrations of 50 and 100 mg/kg and target organisms were
      exposed to the contaminated soil. Germination and emergence of lettuce seedlings
      was found to be dependent upon PCP concentration and soil type, and responses
      were highly correlated to extractable concentrations. Earthworms were sensitive
      to PCP, regardless of soil properties, and mortality was observed in most samples
      at the 100 mg/kg concentration. Toxic responses by the worms were not strongly
      related to soil properties or extractable concentrations. The importance of soil
      chemical and physical properties on toxicity and bioavailability depends upon the
      target organism. In the case of lettuce seedlings, PCP is acquired through the
      aqueous phase; therefore, the chemical interaction between PCP and soil controls
      toxicity. Since earthworms ingest soil and potentially can change the chemical
      environment of exposure, the impact of soil properties on PCP toxicity is less
      apparent.

PMID- 16423719
TI  - Novel fibrous catalyst in advanced oxidation of photographic processing
      effluents.
AB  - A novel fibrous catalyst was used to destroy the pollutants in Kodak Non-Silver
      Bearing (NSB) photographic processing effluents with high chemical oxygen demand
      (COD) value. The oxidation activity of the catalyst was evaluated in terms of COD
      reduction of the effluent. The effects of concentrations of hydrogen peroxide and
      effluent, amount of catalyst, reaction time and temperature on the COD reduction
      were studied. In addition, the combination of catalysis with UV treatment on the
      COD reduction of the effluent was also investigated. Based on the experimental
      results, room temperature is preferred for the catalytic oxidation of NSB
      effluent. It was found that COD reduction of the effluent depends on the amount
      of hydrogen peroxide added to the feed in relation to the mass of catalyst used.
      Significant COD reduction (up to 52%) is achieved after 4 hours of catalytic
      treatment. Extending the duration of catalysis up to 24 hours gives further
      slight decrease in COD value.

PMID- 16423720
TI  - Hg(II) exposure exacerbates UV-induced DNA damage in MRC5 fibroblasts: a comet
      assay study.
AB  - When exposed to UVR, MRC5 fibroblasts incubated with mercuric chloride (0-15
      microM) for 1 hour show increased DNA damage (as measured by the comet assay)
      compared to control cells (UVR irradiated but no mercuric chloride). This
      demonstrates that mercuric chloride and UVR in combination increase DNA damage in
      a synergistic manner. This may have implications to those exposed to mercury as
      it suggests that exposure to mercury in the environment may increase sensitivity
      to sunlight-induced carcinogenesis.

PMID- 16423721
TI  - Study of the chemical interaction between barks and heavy metal cations in the
      sorption process.
AB  - The chemical mechanism displayed in the sorption of heavy metal cations on barks
      was discussed through a modelling study of adsorption in relation to the nature
      of the ligand borne by the chemical components of the bark sorbent. The
      adsorption isotherms of five heavy metal cations (Cr3 +, Cu2 +, Ni2 +, Pb2 +,
      Zn2+) on five species of barks (Sweet chestnut, Oak, Douglas fir, Norway spruce,
      Scots pine species) were studied. The experimental data fitted well the Langmuir
      model, which allowed the expression of the mathematical parameters (qmax, maximum
      binding capacity; b, affinity). The qmax values increased conversely to the b
      values. The correlation of these mathematical values (qmax and b) with the
      analysis of the chemical composition of barks led us to note that Cu2 + interacts
      preferentially with phenolic groups present in lignins and tannins and, opposite
      in, Pb2 + with the carboxylic acid groups in polysaccharides. These observations
      were explained (i) quantitatively by the amount of different types of sites and
      (ii) qualitatively, by the physicochemical characteristics of cations, the nature
      and the tridimensional structure of adsorption sites. Finally, the results
      allowed to define the nature of the chemical interaction (monodentate or
      multidentate complex) between each specified chemical component of barks and each
      kind of heavy metal cations.

PMID- 16423722
TI  - Effects of bismuth contamination on the growth and activity of soil
      microorganisms using thiols as model compounds.
AB  - The present study was undertaken to obtain information about the effects of Bi
      contamination on soil microbial growth and activity using a series of Bi
      complexes with thiol compounds, including mercaptoethanol, thioglycerol,
      mercaptoethylamine, thioglycolic acid, thiomallic acid, reduced glutathione, 2
      mercaptopropionic acid, and L-cysteine. We found that Bi complexes with
      mercaptoethanol, thioglycerol, and mercaptoethylamine, all of which showed
      lipophilicity, markedly inhibited bacterial growth in 1/10 TSB liquid media in
      both Eutric Cambisol (brown forest soil) and Eutric Fluvisol (brown lowland
      soil), with relative CFU of less than 2% at 50 micro M Bi and 6% at 25 micro M
      Bi. However, none of the Bi-thiols, including Highly lipophilic complexes, at 200
      micro M Bi in rosebengal agar medium inhibited fungal growth, possibly because
      fungi have a metabolic system that protects against Bi uptake or detoxifies Bi
      compounds. When soil was contaminated experimentally with Bi-thiol, these
      complexes suppressed soil dehydrogenase activity, particularly in brown forest
      soil, which contains large amounts of easily decomposable organic matter. These
      results indicate that the effects of Bi on soil microbes may depend on mutual
      reactions with organic matter in the environment.

PMID- 16423723
TI  - Fecal contamination of agricultural soils before and after hurricane-associated
      flooding in North Carolina.
AB  - Hurricane Floyd and other storms in 1999 caused widespread and extensive flooding
      of eastern North Carolina and environmental contamination with fecal wastes from
      municipal wastewater and livestock operations. Because wastewater contains high
      levels of pathogenic micro-organisms, principal health risks to humans from
      flooding are consumption of crops grown in fecally contaminated soil and
      ingestion of contaminated water. Flood waters polluted with microbial and other
      contaminants also may be detrimental to the health of livestock and plant crops.
      In the present study, agricultural soils impacted by flood waters were analyzed
      for bacterial and viral indicators of fecal contamination. Total coliforms, fecal
      coliforms, Escherichia coli, spores of Clostridium perfringens, and both male
      specific (F+) and somatic coliphages were recovered from soil and assayed in
      liquid culture media. A number of samples were positive for the presence of fecal
      coliforms, E. coli, and coliphages, indicating the presence of human or animal
      feces. Most samples were positive for total coliforms, and almost all samples
      contained high levels of Cl. perfringens spores. The levels of Cl. perfringens
      spores were significantly (P < 0.001) higher in flooded soil (post-Hurricane
      Floyd) compared to pre-flood soil. Persistent fecal contamination of soil, as
      demonstrated by the high levels of Cl. perfringens spores, suggests the need for
      additional or alternative measures to protect crop-growing areas, including
      prospective microbiological monitoring and improved protection of watersheds from
      incidents capable of releasing fecal material.

PMID- 16423724
TI  - Heuristic for constructing minimum-well groundwater monitoring configurations at
      waste storage facilities.
AB  - A graphical heuristic was designed and evaluated for locating detection wells in
      aquifers beneath landfills. The heuristic identifies locations of a minimum
      number of wells on a compliance boundary to detect potential contaminant releases
      from a landfill. It maximizes gaps between wells while ensuring no potential
      releases pass between them. The solution progresses from one end of a compliance
      boundary to another. Heuristic solutions were compared with output from a second
      method, which equalizes cross-gradient distances between wells, given a specified
      number of wells in a monitoring network. The second approach is superior when
      increasing the number of wells for backup coverage or reducing them to save
      costs. Both approaches maintain high detection efficiency with increased seepage
      velocity or decreased source width relative to design values. To a lesser extent,
      they accommodate variations in flow direction relative to the design direction;
      in test cases, 20-degree variations reduced detection efficiency from 0 to 14%.
      Conjunctively, the approaches can identify effective candidate monitoring
      configurations at landfills.

PMID- 16423725
TI  - Neural network modeling of the kinetics of SO2 removal by fly ash-based sorbent.
AB  - The mechanistic modeling of the sulfation reaction between fly ash-based sorbent
      and SO2 is a challenging task due to a variety reasons including the complexity
      of the reaction itself and the inability to measure some of the key parameters of
      the reaction. In this work, the possibility of modeling the sulfation reaction
      kinetics using a purely data-driven neural network was investigated. Experiments
      on SO2 removal by a sorbent prepared from coal fly ash/CaO/CaSO4 were conducted
      using a fixed bed reactor to generate a database to train and validate the neural
      network model. Extensive SO2 removal data points were obtained by varying three
      process variables, namely, SO2 inlet concentration (500-2000 mg/L), reaction
      temperature (60-80 degreesC), and relative humidity (50-70%), as a function of
      reaction time (0-60 min). Modeling results show that the neural network can
      provide excellent fits to the SO2 removal data after considerable training and
      can be successfully used to predict the extent of SO2 removal as a function of
      time even when the process variables are outside the training domain. From a
      modeling standpoint, the suitably trained and validated neural network with
      excellent interpolation and extrapolation properties could have immediate
      practical benefits in the absence of a theoretical model.

PMID- 16423727
TI  - Organchlorinated pesticides in surface sediments of Meiliang Bay in Taihu Lake,
      China.
AB  - The concentration level of organochlorine pesticides (OCPs) in sediments from
      Taihu Lake, China was investigated to evaluate the potential ecological risk. A
      total of 48 surface sediment samples were collected in Taihu Lake. Meiliang Bay
      in Taihu Lake was selected due to its importance as a drinking water source for
      nearby cities. Results show that the concentrations of various pesticides in
      sediments were in the range of 0.1-107.3 ng/g for HCH, 3.5-50.5 ng/g for
      endosulfan sulfate, 2.7-23.0 ng/g for endosulfan II and 0.3-59.3 ng/g for DDT.
      Among the OCPs, HCHs and DDTs were the most dominant contamnants in the
      sediments. Cyclodiene compounds were also the main pesticides in Taihu lake
      besides HCH and DDT. Among the cyclodiene compounds, heptachlor and endosulfan
      sulfate prevailed in most of the sediments. Moreover, the frequencies of
      detection for the metabolites of PAHs were higher than those of parent compounds,
      depicting that the sediments have been contaminated historically. The results
      obtained in this study shown that there still exist a variety of OCPs residues in
      Taihu Lake and Meiliang Bay.

PMID- 16423726
TI  - Effect of anaerobic digestion and initial pH on metal bioleaching from sewage
      sludge.
AB  - The effects of anaerobic digestion and initial pH on the bioleaching of metals
      from sewage sludge were investigated in shake flask experiments. A strain of
      Acidithiobacillus thiooxidans was employed in the assays using secondary and
      anaerobic sludges, which resulted in similar solubilization yields of the metals
      chromium, copper, lead, nickel, and zinc for both the sludges investigated. The
      effect of initial pH (7.0 and 4.0) on metal bioleaching was assayed by using the
      anaerobic sludge inoculated with indigenous sulfur-oxidizing thiobacilli.
      Although the time required to reach the end of the experiment (final pH close to
      1.0) was shortened at initial pH of 4.0, final metal solubilization was not
      significantly different for both initial pH values, resulting in higher
      solubilization yields for copper, nickel, and zinc (higher than 80%). Chromium
      and lead presented solubilization yields close to 50%. The results obtained in
      this work showed that the metal bioleaching process can be applied to sewage
      sludge regardless of the type of sludge and without the requirement of pH
      adjustment.

PMID- 16423728
TI  - Removal of phthalate esters from aqueous solutions by chitosan bead.
AB  - Removal of phthalate esters (PAEs) by chitosan bead in aqueous solution was
      studied. The adsorption isotherms of PAEs by chitosan bead were well described by
      Freundlich isotherm equations. Results of kinetic experiments indicated that
      diheptyl phthalate (DHpP) had the highest adsorption capacity (1.52 mg/g) among
      six PAEs in our research. PAE adsorption efficiency by chitosan bead was examined
      in both batch and continuous systems, and DHpP attained 74.9% recovery efficiency
      from chitosan bead by shaking with an equal volume mixture of methanol and water.
      The recovered chitosan bead was reusable as an adsorbent. The influences of
      temperature, pH, Ca+2, and NaCl on PAE adsorption were also evaluated to
      determine performance in different water environments (e.g., groundwater, surface
      water, and sea water). The results showed that PAE adsorption decreased as
      temperature increased. From pH experiments it appeared that pH 8.0 was optimal
      for adsorption. The effect of Ca+2 showed that adsorption efficiency did not
      change by increasing the concentrations of Ca+2 until 400 mg/L. NaCl coexistence
      showed an insignificant effect on PAE adsorption. Furthermore, the chitosan bead
      was also applied to treating the discharge of a plastics plant, and the treatment
      results resembled those of a laboratory continuous system. This is the first
      report to use chitosan bead as an adsorbent to adsorb phthalate esters from
      aqueous solution. These results indicate that the application of chitosan bead is
      feasible in the aqueous environments of Taiwan.

PMID- 16423729
TI  - What is Christian about Christian bioethics? Metaphysical, epistemological, and
      moral differences.

PMID- 16423730
TI  - So finally, what is Christian about Christian bioethics?
AB  - The author criticizes the essays in this issue by Waters, Erickson, Trotter and
      Verhey for not placing an adequate Christology at the center of their definitions
      what is Christian bioethics.

PMID- 16423731
TI  - On the Christian in Christian bioethics.
AB  - What is Christian about Christian bioethics? And is an authentically Christian
      bioethics a practical possibility in the world in which we find ourselves? In my
      essay I argue that personhood and the personal are so fundamental to the
      Christian understanding of our humanity that body, soul, and spirit are probably
      best understood as the components of a triune (as opposed to dual) aspect theory
      of personhood. To confess to a Christian bioethics is to admit that Christians
      cannot pretend fully to understand either cures or their meaning. However
      effective and "knowledge-based" contemporary medical interventions are, a
      Christian must humbly and honestly confess a lack of complete knowledge on both
      levels. At the same time, a Christian bioethicist must express a total personal
      commitment to Christian Faith.

PMID- 16423732
TI  - What is Christian about Christian bioethics?
AB  - What is Christian about Christian bioethics? The short answer to this question is
      that the Incarnation should shape the form and content of Christian bioethics. In
      explicating this answer it is argued that contemporary medicine is unwittingly
      embracing and implementing the transhumanist dream of transforming humans into
      posthumans. Contemporary medicine does not admit that there are any limits in
      principle to the extent to which it should intervene to improve the quality of
      human life. This largely inarticulate, yet ambitious, agenda is derived first in
      late modernity's failed, but nonetheless ongoing, attempt to transform necessity
      into goodness, and second the loss of any viable concept of eternity, thereby
      stripping temporal existence of any normative significance. In short, medicine
      has become the vanguard of a profane attempt to save humankind by extracting data
      from flesh. In response, it is contended that an alternative Christian bioethics
      must be shaped by the Incarnation, the Word made flesh. This assertion does not
      entitle Christians to oppose the posthuman trajectory of contemporary medicine on
      the basis of any natural or biological essentialism. Rather, it is an evangelical
      witness to the grace of Christ's redemption instead of the work of self
      transformation. It is Christ alone who thereby makes the vulnerability and
      mortality of finitude a gift and blessing. Specifically, it is maintained that
      the chasm separating necessity and goodness cannot be filled but only bridged
      through the suffering entailed in Christ's cross, and through Christ's
      resurrection eternity becomes the standard against which the temporal lives of
      human creatures are properly formed and measured. Consequently, Christian
      bioethics should help us become conformed to Christ rather than enabling self
      transformation.

PMID- 16423733
TI  - What makes Christian bioethics Christian? Bible, story, and communal discernment.
AB  - Scripture is somehow normative for any bioethic that would be Christian. There
      are problems, however, both with Scripture and with those who read Scripture.
      Methodological reflection is necessary. Scripture must be read humbly and in
      Christian community. It must be read not as a timeless code but as the story of
      God and of our lives. That story moves from creation to a new creation. At the
      center of the Christian story are the stories of Jesus of Nazareth as healer,
      preacher of good news to the poor, and sufferer. The story shapes character and
      conduct and enables communal discernment.

PMID- 16423734
TI  - Bioethics, Christian charity and the view from no place.
AB  - This essay contrasts the notions of charity employed by Traditional Christianity
      and by liberal cosmopolitan bioethics, arguing that: (1) bioethics attempts to
      reconstruct the notion of charity in a manner that is caustic to the Traditional
      Christian moral vision, (2) Christians are, on the whole, more charitable than
      proponents of bioethics' reconstructed view (even given the standards of the
      latter), and (3) the theistically oriented conception of charity employed by
      Traditional Christianity cannot be expressed in bioethics' purportedly neutral
      public vocabulary. The upshot is that, in the name of neutrality and pluralism,
      liberal cosmopolitan bioethicists seek to impose an impoverished moral vocabulary
      that reflects liberal cosmopolitan ideology while excluding input from
      Traditional Christianity and other non-liberal-humanistic moral visions.

PMID- 16423735
TI  - Christian bioethics and the Church's political worship.
AB  - Christian bioethics springs from the worship that is the response of the Church
      to the Gospel of Jesus Christ. Such worship is distinctively political in nature,
      in that it acknowledges Christ as Lord. Because it is a political worship, it can
      recognize no other lords and no other prior claims on its allegiance: these
      include the claims of an allegedly universal ethics and politics determined from
      outside the Church. However the Church is called not just to be a contrast
      society, but also to witness to the freeing of the world from salvific
      pretensions in order that it may embrace its proper temporality. The implications
      of this for the distinctiveness of Christian bioethics are brought out in three
      movements: first, the Church's itself learning how it is to conceive bioethics;
      second, the Church's role in unmasking the idols of secular bioethics; and third,
      the Church's witnessing to the freeing of medicine from idolatrous aspirations.

PMID- 16423736
TI  - Christian bioethics, secular bioethics, and the claim to cultural authority.
AB  - Though the papers in this volume for the most part address the question, "What is
      Christian about Christian Bioethics", this paper addresses instead a closely
      related question, "How would a Christian approach to bioethics differ from the
      kind of secular academic bioethics that has emerged as such an important field in
      the contemporary university?" While it is generally assumed that a secular
      bioethics rooted in moral philosophy will be more culturally authoritative than
      an approach to bioethics grounded in the contingent particularities of a
      religious tradition, I will give reasons for rejecting this assumption. By
      examining the history of the recent revival of academic bioethics as well as the
      state of the contemporary moral philosophy on which it is based I will suggest
      that secular bioethics suffers from many of the same liabilities as a carefully
      articulated Christian bioethics. At the end of the paper I will turn briefly to
      examine the question of how, in light of this discussion, a Christian bioethics
      might best be pursued.

PMID- 16423737
TI  - The impact of stress on neutral and emotional aspects of episodic memory.
AB  - The present experiment demonstrates that exposure to a significant psychological
      stressor (administered before watching a slide show) preserves or even enhances
      memory for emotional aspects of an event, and simultaneously disrupts memory for
      non-emotional aspects of the same event. Stress exposure also disrupted memory
      for information that was visually and thematically central to the event depicted
      in the slide show. Memory for peripheral information, on the other hand, was
      unaffected by stress. These results are consistent with theories invoking
      differential effects of stress on brain systems responsible for encoding and
      retrieving emotional memories (the amygdala) and non-emotional memories (e.g.,
      the hippocampal formation), and inconsistent with the view that memories formed
      under high levels of stress are qualitatively the same as those formed under
      ordinary emotional circumstances. These data, which are also consistent with
      results obtained in a number of studies using animals and humans, have
      implications for the traumatic memory debate and theories regarding human memory.

PMID- 16423738
TI  - Omitting details from post-event information: are true and false memory affected
      in the same way?
AB  - Participants who witness an event and later receive post-event information that
      omits a critical scene are less likely to recall and to recognise that scene than
      are participants who receive no post-event information (Wright, Loftus, & Hall,
      2001). The present study used the Deese-Roediger-McDermott (DRM) paradigm, in
      which participants study lists of semantic associates (e.g., hot, snow, warm,
      winter) that commonly elicit false memories of critical non-presented words
      (e.g., cold), to determine whether omitting information from a second
      presentation decreases memory for both presented and non-presented information.
      Participants were presented with a list of the semantic associates of six non
      presented words. For half the participants, this list was presented a second time
      with the semantic associates of one of the non-presented words omitted. As
      expected, participants were less likely to recall and to recognise the presented
      words when they had been omitted from the second presentation. Omission also
      decreased the rate at which non-presented words were recalled, although false
      recognition of these words was not reduced. These results suggest that false
      recognition may be particularly difficult to attenuate and that post-event
      omission may be more detrimental to memory accuracy than previously thought.

PMID- 16423739
TI  - Remembering a criminal conversation: beyond eyewitness testimony.
AB  - Unlike the important body of work on eyewitness memory, little research has been
      done on the accuracy and completeness of "earwitness" memory for conversations.
      The present research examined the effects of mode of presentation (audiovisual/
      auditory-only) on witnesses' free recall for utterances in a criminal
      conversation at different retention intervals (immediate/delayed) within a single
      experiment. Different forms of correct recall (verbatim/gist) of the verbal
      information as well as different types of errors (distortions/fabrications) were
      also examined. It was predicted that participants in the audiovisual modality
      would provide more correct information, and fewer errors than participants in the
      auditory-only modality. Participants' recall was predicted to be impaired over
      time, dropping to a greater extent after a delay in the auditory-only modality.
      Results confirmed these hypotheses. Interpretations of the overall findings are
      offered within the context of dual-coding theory, and within the theoretical
      frameworks of source monitoring and fuzzy-trace theory.

PMID- 16423740
TI  - Suggestibility and state anxiety: how the two concepts relate in a source
      identification paradigm.
AB  - Source identification tests provide a stringent method for testing the
      suggestibility of memory because they reduce response bias and experimental
      demand characteristics. Using the techniques and materials of Maria Zaragoza and
      her colleagues, we investigated how state anxiety affects the ability of
      undergraduates to identify correctly the source of misleading post-event
      information. The results showed that individuals high in state anxiety were less
      likely to make source misattributions of misleading information, indicating lower
      levels of suggestibility. This effect was strengthened when forgotten or non
      recognised misleading items (for which a source identification task is not
      possible) were excluded from the analysis. Confidence in the correct attribution
      of misleading post-event information to its source was significantly less than
      confidence in source misattributions. Participants who were high in state anxiety
      tended to be less confident than those lower in state anxiety when they correctly
      identified the source of both misleading post-event information and non-misled
      items. The implications of these findings are discussed, drawing on the
      literature on anxiety and cognition as well as suggestibility.

PMID- 16423741
TI  - Collaborative remembering of emotional events: the case of Rabin's assassination.
AB  - Individual and collaborative remembering of the assassination of Israel's Prime
      Minister, Itzhak Rabin, were compared. In line with previous laboratory findings
      on memory of neutral stimuli, it was hypothesised that collaborative remembering
      (three individuals reaching a common response) and nominal remembering (three
      individual responses pooled together) of the assassination would be more accurate
      than individual remembering. A total of 146 participants responded (115
      individually and 120 in groups of three) to open-ended and multiple-choice
      questionnaires (among them, 89 responded twice with a week of intertest interval)
      about Rabin's assassination and the events that preceded and followed it. Data
      analysis showed that the collaborative responses to the open-ended questionnaire
      contained more details (both accurate and inaccurate) than the individual
      responses, and that the responses to the multiple-choice questionnaire were more
      accurate than the individual responses. However, the collaborative responses
      contained fewer details (both accurate and inaccurate) than the nominal
      responses. Responses to the two questionnaires were more accurate on the retest
      when they followed collaborative rather than individual responses on the original
      test. The inferiority of the collaborative relative to the nominal remembering
      was attributed to collaborative inhibition, whereas the positive effect of
      collaborative remembering on performance on the retest was attributed to the
      contribution of contextual cues.

PMID- 16423742
TI  - Adult recollections of earliest childhood dreams: a cross-cultural study.
AB  - In two studies, Caucasian and Asian college students recalled their earliest
      memory of a dream, and they provided information about behaviours and beliefs
      associated with dreaming. Consistent with previous research on childhood amnesia,
      participants rarely recounted dreams that occurred before age 3. In Study 1, the
      mean age of the earliest dream memory was 14 months earlier for Caucasians than
      for Asians. In Study 2, more Asians than Caucasians were unable to remember a
      childhood dream. Dream-related behaviours and beliefs also differed markedly
      across cultures. Compared to Asians, Caucasians reported talking more frequently
      with parents about their dreams in childhood, receiving stronger parental
      encouragement to share dreams, and feeling more comfortable doing so. Caucasians
      also reported sharing their dreams with others more frequently in adulthood and
      they assigned greater value to their dreams. Most Caucasians but few Asians
      consented to the researchers' request to send parents a questionnaire concerning
      the participant's childhood dreams. The results support the social interaction
      explanation for autobiographical memory development, in which parent-child
      conversations about the personal past contribute to memory accessibility.

PMID- 16423743
TI  - The difference between implicit and explicit associative processes at study in
      creating false memory in the DRM paradigm.
AB  - The effects of implicit and explicit associative processes for false recognition
      were examined by manipulating exposure duration of studied items; 20 ms or 2000
      ms. Participants studied lists of words that were high associates to a
      nonpresented word (critical lure) in either condition. After learning each list,
      they took a recognition test and remember/know judgements immediately (Experiment
      1) or 1 minute later (Experiment 2). In Experiment 1, know responses for critical
      lures were more in the 20 ms than in the 2000 ms conditions, while remember
      responses for them were more in the 2000 ms condition. Implicit associative
      processes create familiarity of critical lures, and explicit associative
      processes create details of false memories. Comparing the results of Experiment 1
      with those of Experiment 2, remember responses for critical lures were increased
      with the prolonged time only in the 20 ms condition. Characteristics of false
      memory made by implicit associative processes could be changed by prolonged time.

PMID- 16423744
TI  - Effect of retention interval on the simultaneous cognate-noncognate and remember
      know mirror effects.
AB  - Recognition memory for Spanish-Catalan cognate and noncognate words was tested at
      retention intervals of 30 minutes, 3 days, and 7 days using a remember/know
      response procedure. We observed a clear mirror effect for the cognate-noncognate
      stimulus class and a remember-know response categorisation at the immediate
      retention interval. However, the cognate and noncognate mirror was still observed
      at 3 and 7 days, whereas the remember-know mirror disappeared at both retention
      intervals. Also, we ran a repeated testing condition to be able to carry out a
      sequential item analysis and observe the fate of the original remember and know
      responses 3 or 7 days later. The analysis supported the idea that there was a
      loss of contextual information that was at the root of the disappearance of the
      remember-know mirror effect. These results provide support to the idea that it is
      the imbalance between recollection and familiarity that is the most likely cause
      of the mirror effect.

PMID- 16423745
TI  - Memories of uncertain origin: dreamt or real?
AB  - The existence of a memory whose origin, real or dreamt, was uncertain was
      reported by just over half of an undergraduate sample of 358. Each respondent
      described one such memory if they had one. The memories were typically of mundane
      events, although 10 respondents described possible crimes. Respondents were often
      concerned to resolve the origin of these memories. Their plausibility, vividness,
      and how well the events fitted into one's life were often considered by the
      respondents, but where resolution occurred it was frequently based on evidence
      obtained from the physical or social environment. The reported qualities of the
      event did not correlate with whether the respondent thought it more likely to
      have been originally a dream or a real event.

PMID- 16423746
TI  - Effects of the timing and identity of retrieval cues in individual recall: an
      attempt to mimic cross-cueing in collaborative recall.
AB  - Inhibitory effects in collaborative recall have been attributed to cross-cueing
      among partners, in the same way that part-set cues are known to impair recall in
      individuals. However, studies of part-set cueing in individuals typically involve
      presenting cues visually at the start of recall, whereas cross-cueing in
      collaboration is likely to be spoken and distributed over time. In an attempt to
      bridge this gap, three experiments investigated effects of presenting spoken part
      set or extra-list cues at different times during individual recall. Cues had an
      inhibitory effect on recollection in the early part of the recall period,
      especially when presented in immediate succession at the start of recall. There
      was no difference between the effects of part-set and extra-list cues under these
      presentation conditions. However, more inhibition was generated by part-set than
      extra-list cues when cue presentation was distributed throughout recall. These
      results are interpreted as suggesting that cues presented during recall disrupt
      memory in two ways, corresponding to either blocking or modifying retrieval
      processes. Implications for explaining and possibly ameliorating inhibitory
      effects in collaborative recall are discussed.

PMID- 16423747
TI  - Pre-event stereotypes and misinformation effects in young children.
AB  - This study examined the effects of pre-event stereotypes on 5-year-old children's
      memories for the visit of an adult male to their school. Children were read three
      stories in which this man was described in positive, negative, or neutral terms.
      Following the visit, children were read post-event narratives which contained
      positive and negative misinformation that was consistent and inconsistent with
      the pre-event stereotype. Children were then given a recognition test under
      inclusion and exclusion instructions. Negative misinformation was correctly
      rejected more often than positive misinformation. Children given a positive pre
      event stereotype were more likely to accept positive misinformation than those in
      the other stereotype conditions. Process dissociation analyses revealed that
      recollection for negative misinformation was larger than for positive
      misinformation; the opposite was the case for familiarity.

PMID- 16423748
TI  - Re-exposure to studied items at test does not influence false recognition.
AB  - In two experiments, we investigated whether re-exposure to previously studied
      items at test affects false recognition in the DRM paradigm. Furthermore, we
      examined whether exposure to the critical lure at test influences memory for
      subsequently presented study items. In Experiment 1, immediately following each
      studied DRM list, participants were given a recognition test. The tests were
      constructed such that the number of studied items preceding the critical lure
      varied from zero to five. Neither false recognition for critical lures nor
      accurate memory for studied items was affected by this manipulation. In
      Experiment 2, we replicated this pattern of results under speeded conditions at
      test. Both experiments confirm that exposure to previously studied items at test
      does not affect true or false recognition in the DRM paradigm. This pattern
      strongly suggests that retrieval processes do not influence false recognition in
      the DRM paradigm.

PMID- 16423750
TI  - Effects of waterbolus size, shape and configuration on the SAR distribution
      pattern of the Lucite cone applicator.
AB  - The effects of waterbolus dimensions and configuration on the effective field
      size (EFS) of the Lucite cone applicator (LCA) for superficial hyperthermia are
      presented. The goal of the research is to develop guidelines which mark out a sub
      set of optimal LCA-waterbolus set-ups. The effects of variations in (i)
      waterbolus thickness, (ii) waterbolus area, (iii) waterbolus length/width ratio
      and (iv) eccentric placement of the applicator have been investigated in an FDTD
      model study. The prominent effects are verified with IR thermography
      measurements. An optimal EFS value of 80 cm2 is found for waterbolus area of 200
      400 cm2. A small (10 x 10 cm2) waterbolus area restricts the EFS to 25% of the
      optimal value. The sensitivity to sub-optimal waterbolus area and length/width
      ratio increases with waterbolus height. Eccentric placement of the LCA near the
      waterbolus edge reduces the EFS to up to 50% of the optimal value. The IR
      measurements confirm the model findings. Based on the results, the following
      guidelines for the clinical application of the LCA have been defined: the
      waterbolus (i) should extend the LCA aperture at least 2.5 cm, especially at the
      Lucite windows, and (ii) the height should not exceed 2 cm.

PMID- 16423749
TI  - Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia for pain
      relief of unresectable and recurrent colorectal cancer.
AB  - PURPOSE: The purpose of this study was to assess the pain relief in patients with
      unresectable and recurrent colorectal cancer treated with radiation plus 8 MHz
      radiofrequency-capacitive regional hyperthermia and to identify predictors of the
      good outcome. METHODS: Between February 1986-May 2003, 41 patients with primarily
      unresectable and recurrent colorectal cancer that caused pain were treated with
      thermoradiotherapy at the hospital and retrospectively analysed. Radiotherapy was
      administered with a mean total radiation dose of 56 Gy. Hyperthermia was usually
      applied within 30 min after radiotherapy once or twice a week. For cooling of the
      skin surface, the overlay boluses were applied in addition to regular boluses.
      The external cooling unit has been used to reinforce the cooling ability of the
      overlay bolus and achieve strong surface cooling to reduce the preferential
      heating of the subcutaneous fat tissue and treat with more RF-output in 17
      patients since January 1997. RESULTS: Pain relief was obtained in 83% of the
      patients. Multi-variate analysis by logistic regression to evaluate the effects
      of certain factors on pain relief (complete response + good response) was
      strongly correlated with the presence of radiating pain to leg(s) (p < 0.05). The
      median follow-up was 18 months. The median duration of pain relief was 7.0
      months. For the 27 patients in whom the tumour temperature was estimated, the
      median duration of pain relief was 14.6 months for the patients with a mean
      average tumour temperature of > 42.5 degrees C and 5.7 months for those of < 42.5
      degrees C (p < 0.05). In the 18 patients with radiating pain to leg(s), use of
      strong superficial cooling and the higher numbers of hyperthermia treatments were
      better prognostic factors for the duration of pain relief (p < 0.01 and p < 0.05,
      respectively). CONCLUSIONS: Radiotherapy with 8 MHz radiofrequency-capacitive
      regional hyperthermia provided an efficient, effective means on pain relief of
      treating unresectable and recurrent colorectal cancer. The duration of pain
      relief can be prolonged, if an adequate heating is achieved, especially in the
      patients with radiating pain to the leg(s).

PMID- 16423751
TI  - MR thermometry-based feedback control of efficacy and safety in minimum-time
      thermal therapies: phantom and in-vivo evaluations.
AB  - The experimental validation of a model-based, thermal therapy control system
      which automatically and simultaneously achieves the specified efficacy and safety
      objectives of the treatment is reported. MR-thermometry measurements are used in
      real-time to control the power of a stationary, focused ultrasound transducer in
      order to achieve the desired treatment outcome in minimum time without violating
      the imposed safety constraints. Treatment efficacy is quantified in terms of the
      thermal dose delivered to the target. Normal tissue safety is ensured by
      automatically maintaining normal tissue temperature below the imposed limit in
      the user-specified locations. To reflect hardware limitations, constraints on the
      maximum applied power are also imposed. At the pretreatment stage, MR imaging and
      thermometry are used to localize the treatment target and identify thermal and
      actuation models. The results of phantom and canine experiments demonstrate that
      spatially-distributed, real-time MR temperature measurements enhance one's
      ability to robustly achieve the desired treatment outcome in minimum time without
      violating safety constraints. Post-treatment evaluation of the outcome using T2
      weighted images of canine muscle showed good spatial correlation between the
      sonicated area and thermally damaged tissue.

PMID- 16423752
TI  - Alterations in heat-induced radiosensitization accompanied by nuclear structure
      alterations in Chinese hamster cells.
AB  - This paper examined heat-induced radiosensitization in two Chinese hamster heat
      resistant cell lines, HR-1 and OC-14, that were isolated from the same wild-type
      HA-1 cell line. It found a reduction of the magnitude of heat-induced
      radiosensitization after exposure to 43 degrees C in both HR-1 and OC-14 cells
      and a similar reduction after exposure to 45 degrees C in HR-1 cells, but not in
      OC-14 cells. The effect of heat exposure on a class of ionizing radiation-induced
      DNA damage that inhibits the ability of nuclear DNA to undergo super-coiling
      changes was also studied using the fluorescent halo assay in these three cell
      lines. Wild type cells exposed to either 43 or 45 degrees C before irradiation
      had a DNA rewinding ability that was intermediate between control and unheated
      cells, a phenomenon previously described as a masking effect. This masking effect
      was significantly reduced in HR-1 cells exposed to either 43 or 45 degrees C or
      in OC-14 cells exposed to 43 degrees C under conditions that heat-induced
      radiosensitization was reduced. In contrast, the masking effect was not altered
      in OC-14 cells exposed to 45 degrees C, conditions under which heat-induced
      radiosensitization was similar to that observed in wild-type HA-1 cells. These
      results suggest that a reduction in the masking effect is associated with a
      reduction of the magnitude of heat-induced radiosensitization in the HR-1 and OC
      14 heat-resistant cell lines. The reduction of the masking effect in the cell
      lines resistant to heat-induced radiosensitization was associated with neither a
      reduction in the magnitude of the heat-induced increase in total nuclear protein
      content nor major differences in the protein profiles of the nucleoids isolated
      from heated cells.

PMID- 16423754
TI  - Cell cycle dependent apoptosis and cell cycle blocks induced by hyperthermia in
      HL-60 cells.
AB  - The effects of heat are strongly dependent on the time of heating at a given
      temperature. The relationship between treatment time and temperature for a
      biological isoeffect (the Arrhenius plot) has been confirmed for a variety of
      normal tissues and tumours. A marked change of slope occurs somewhere between 42
      43 degrees C. Above this transition temperature the slope is constant for a
      variety of cells and tissues. Therefore, when defining thermal doses in
      hyperthermia studies, both the time and temperature of heating are equally
      important determinants. In this study, cell cycle progression and apoptosis were
      analysed in HL-60 cells after heating from 5-60 min at 45.0 degrees C and also
      heating with five different iso-dose time-temperature heat treatments. A heat
      shock of 5-15 min at 45.0 degrees C caused the accumulation of cells in G1 and
      G2/M phases after 12 h at 37 degrees C, whereas a heat shock of 20-60 min at 45.0
      degrees C reduced the number of non-apoptotic cells in all phases because the
      number of apoptotic cells increased. The fraction of apoptotic cells followed a
      sigmoid curve as the heating time increased from 5-60 min at 45.0 degrees C. Cell
      cycle analysis showed that apoptosis occurred predominantly in S-phase cells for
      shorter heating times but in all phases at longer times. An isodose heat shock
      lower than 44.0 degrees C (42.0-43.0 degrees C) gave the same apoptotic index,
      while heat shock from 44.0-46.0 degrees C caused a greater than expected
      apoptotic index. Thus, there was a transition at 44.0 degrees C in HL-60 cells,
      above which apoptosis increased rapidly. These results indicate that isodose
      analysis based on clonogenic survival in fibroblast cells may not be relevant for
      cell types which readily undergo apoptosis. Clonogenic survival was also compared
      with apoptosis for HL-60 cells and an apoptotic-resistant derivative cell line,
      HWC-2, heated for various times at 45.0 degrees C. Survival based on a clonogenic
      assay was much lower than survival based only on apoptotic index at all times for
      HL-60 cells. HWC-2 cells did not undergo apoptosis and also had a higher
      clonogenic survival than HL-60 cells.

PMID- 16423753
TI  - Response to pulsed dose rate and low dose rate irradiation with and without mild
      hyperthermia using human breast carcinoma cell lines.
AB  - The purpose of this study was to establish whether a pulsed dose rate (PDR)
      treatment of 1.5 Gy given every 3 h in combination with 41 degrees C mild
      hyperthermia or a continuous low dose rate (LDR) treatment with mild hyperthermia
      could radiosensitize two isogenic human breast carcinoma cell lines in comparison
      to pulsed dose rate or low dose rate irradiation alone. The radiation resistant
      cell line was derived from the parental cell line and was transfected to over
      express DNA polymerase beta. The end-points assessed were the survival of the
      cells using the clonogenic assay, the amount of residual DSB(s) using the comet
      assay and gene expression of polymerase beta using RT-PCR. Results showed that
      the PDR and LDR treatments combined with mild hyperthermia caused significant
      radiosensitization when compared to PDR and LDR irradiation alone in terms of the
      clonogenic and comet assays with both cell lines. RT-PCR results showed that
      polymerase beta levels of expression were not elevated in response to these
      treatments, implying that this polymerase may not be involved in sub-lethal
      damage repair or thermal radiosensitization. These results suggest a potential
      clinical advantage when combining LDR or PDR with hyperthermia, since they
      indicate that hyperthermia is an effective radiosensitizer.

PMID- 16423755
TI  - Fluidized bed microencapsulation: thermodynamics of aqueous and ethanolic coating
      processes.
AB  - This paper aims to provide the fluidized bed scientist with appropriate and
      simple tools for the elaboration of efficient experimental designs of
      microencapsulation processes by fluidized bed using any combination of solvent
      and gas. Psychometric charts are used to predict and optimize experimental
      parameters in microencapsulation by fluidized bed evaporative cooling processes.
      This paper shows that theoretical psychometric charts for water-air, ethanol-air
      and, by extrapolation, and solvent-gas mixtures can be developed from simple
      thermodynamic equations. The psychometric charts are constructed from readily
      available or calculable physical data such as the heat capacities of the gas and
      the solvent, the latent heat of vapourization of the solvent and the saturation
      concentration of the solvent in the fluidization gas. The calculated psychometric
      chart for water-air mixtures presented in this paper is shown to agree very well
      with the generally accepted charts found in the literature. An ethanol-air
      psychometric chart is built using the same equations and compared to experimental
      data of evaporative cooling processes using ethanol as the solvent. The paper
      shows a very good agreement between the calculated psychometric charts and the
      empirical data obtained from both ethanol-based and water-based evaporative
      cooling experiments. The results show the soundness and the relevance of the
      theoretical development behind the construction of the calculated psychometric
      charts; the accuracy of any other solvent-gas psychometric charts built using the
      equations proposed in this paper can be rightly extrapolated.

PMID- 16423756
TI  - Vancomycin biodegradable poly(lactide-co-glycolide) microparticles for bone
      implantation. Influence of the formulation parameters on the size, morphology,
      drug loading and in vitro release.
AB  - The present study investigates vancomycin microencapsulation in biodegradable
      PLAGA microparticles. To optimize encapsulation efficiency by the double emulsion
      (w/o/w) solvent evaporation/extraction process, two parameters were studied:
      surfactant (Span 80) rate and external aqueous phase saturation. In vitro
      dissolution studies, laser granulometry and scanning electron microscopy were
      performed to characterize the microparticles. The best results were obtained by
      stabilizing the first emulsion with 0.5% Span 80 and saturating the external
      phase with sodium chloride. Such parameters allowed a 95% drug encapsulation
      efficiency. This process yielded round microparticles with a mean diameter of
      approximately 170 microm and presenting a smooth surface without any pores.
      Moreover, this formulation induces a sustained drug release at a constant rate
      over a period of 10 days. Such materials could be associated with biphasic
      calcium phosphate granules to form an antibiotic-loaded injectable bone
      substitute offering a long-term activity in situ.

PMID- 16423757
TI  - The relation between narrow-dispersed microcapsules and surfactants.
AB  - Electric ink display is one of the prospect technologies in paper-like display.
      In this paper, electric ink microcapsules are prepared by means of an in situ
      polymerization and complex coacervation. In order to obtain the microcapsules in
      a uniform size distribution, this study focused on the inter-facial tension
      between tetrachloroethylene and water solution, the dispersion of the core
      droplets and the microencapsulation with different kind of surfactants. By
      measuring the inter-facial tensions between water and tetrachloroethylene, it is
      found that urea-formaldehyde (UF) pre-polymer presents certain surface activity
      due to the inter-facial tension descending from 43 mN m(-1) to 35 mN m(-1).
      Because the surface activity of pre-polymer is not valid, the water-soluble
      emulsifiers can occupy on the surface of the droplets and prevent the UF resin
      depositing there. The analysis of the size distribution shows that the UF
      microcapsules are multi-dispersed. Furthermore, the influence of anionic
      surfactant of SDS on the size distribution of the core droplets is also
      investigated. The average diameters of the core droplets prepared with 0.005 wt%
      and 0.012 wt% SDS are approximately 50 microm and 28 microm, respectively. That
      reveals the existence of SDS not only decreases the droplet diameters, but also
      makes the size distribution centralized. Because the surface of the core droplets
      is charged due to the absorption of SDS anionic, the Gelatin and Gum Arabic (GA)
      coacervating layer is easy to form there. The size of the GA microcapsules
      prepared with 0.003 wt% SDS is approximately 65 microm. Finally; the responsive
      behaviour of the microcapsules to electric field is also investigated.

PMID- 16423758
TI  - Formulation and in vitro evaluation of ethyl cellulose microspheres containing
      zidovudine.
AB  - The aim of this study was to formulate and evaluate microencapsulated controlled
      release preparations of zidovudine using ethyl cellulose as the retardant
      material with high entrapment efficiency and extended release. Microspheres were
      prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method.
      A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a
      1:1 ratio and light liquid paraffin were chosen as primary and secondary oil
      phases, respectively. Span 80 was used as the surfactant for stabilizing the
      secondary oil phase. The prepared microspheres were white, free flowing and
      spherical in shape and characterized by drug loading, infrared spectroscopy (IR),
      differential scanning colorimetry (DSC) and scanning electron microscopy (SEM).
      The in vitro release studies were performed using PH 7.4 phosphate buffer. The
      drug loaded microspheres showed 41-55% of entrapment and release was extended up
      to 18-20 h. The infrared spectra and DSC and DTA thermograms showed stable
      character of zidovudine in the drug loaded microspheres and revealed the absence
      of drug-polymer interactions. SEM studies showed that the microspheres are
      spherical and porous in nature. Data obtained from in vitro release were fitted
      to various kinetic models and high correlation was obtained in the Higuchi model.
      The drug release was found to be diffusion controlled.

PMID- 16423759
TI  - Formulation and in-vitro characterization of retinoic acid loaded poly (lactic-co
      glycolic acid) microspheres.
AB  - Poly (lactic-co-glycolic acid) (PLGA) microspheres containing all-trans retinoic
      acid (atRA) were prepared by emulsion/solvent evaporation technique. PLGA (50:50)
      with inherent viscosities of 0.17 and 0.39 dL g(-1) was used. Polyvinyl alcohol
      (PVA) or PVA and sodium oleate (SO) combinations (4:1) were used to stabilize the
      emulsions. The effect of polymer viscosity, emulsifier type and concentration on
      the in vitro release of atRA from the microspheres was investigated. The
      stability of the microparticles was also tested at the temperatures of 4, 25 and
      40 degrees C. The particle size ranged between 1-2 microm. Microspheres were
      smooth and spherical in shape, as determined by scanning electron microscope
      (SEM) photographs. The yield of microspheres ranged from 50-75% and the
      encapsulation efficiency was determined between 45-75%. In vitro release studies
      showed that atRA release from microspheres lasted for 11 days.

PMID- 16423760
TI  - Liquid phase coating to produce controlled-release alginate microspheres.
AB  - This study explored a liquid phase coating technique to produce polymethyl
      methacrylate (PMMA)-coated alginate microspheres. Alginate microspheres with a
      mean diameter of 85.6 microm were prepared using an emulsification method. The
      alginate microspheres, as cores, were then coated with different types of PMMA by
      a liquid phase coating technique. The release characteristics of these coated
      microspheres in simulated gastric (SGF) and intestinal (SIF) fluids and the
      influence of drug load on encapsulation efficiency were studied. The release of
      paracetamol, as a model hydrophilic drug, from the coated microspheres in SGF and
      SIF was greatly retarded. Release rates of Eudragit RS100-coated microspheres in
      SGF and SIF were similar as the rate-controlling polymer coat was insoluble in
      both media. Drug release from Eudragit S100-coated microspheres was more
      sustained in SGF than in SIF, due to the greater solubility of the coating
      polymer in media with pH greater than 7.0. The drug release rate was affected by
      the core:coat ratio. Drug release from the coated microspheres was best described
      by the Higuchi's square root model. The liquid phase coating technique developed
      offers an efficient method of coating small microspheres with markedly reduced
      drug loss and possible controlled drug release.

PMID- 16423761
TI  - Drug release from core-shell type nanoparticles of poly(DL-lactide-co-glycolide)
      grafted dextran.
AB  - This study prepared core-shell type nanoparticles of a poly(DL-lactide-co
      glycolide) (PLGA) grafted-dextran. The synthesis of the PLGA-dextran conjugate
      was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. The PLGA
      grafted-dextran was able to form nanoparticles in water by self-assembly and
      their particle size was 245.3 +/- 95.1 nm. From fluorescence probe study using
      pyrene as a hydrophobic probe, critical association concentration (CAC) values
      were determined from the fluorescence excitation spectra and were found to be
      0.006 g l(-1). Morphological observations using a scanning electron microscope
      (SEM) showed that the polymeric nanoparticles of the PLGA-dextran conjugate have
      uniformly spherical shapes. Their size and morphology provide them with
      acceptable properties for use as a drug-targeting carriers. Drug release from
      core-shell type nanoparticles was faster in the presence of dextranase,
      indicating that core-shell type nanoparticles of PLGA grafted-dextran can be used
      as an oral drug carriers.

PMID- 16423765
TI  - Changing the presumption: providing ART to vaccine research participants.

PMID- 16423766
TI  - Oocyte and somatic cell procurement for stem cell research: the South Korean
      experience.

PMID- 16423767
TI  - A commentary on oocyte donation for stem cell research in South Korea.

PMID- 16423768
TI  - When the trough breaks.

PMID- 16423770
TI  - Bioterror and public health infrastructure: a response to commentators.

PMID- 16423771
TI  - Letter to the editor: The doctor-patient relationship in the age of evidence
      based health care (and not the "post-managed care era"): a response to G. Caleb
      Alexander and John D. Lantos.

PMID- 16423772
TI  - Deception, catholicism, and hope: understanding problems in the communication of
      unfavorable prognoses in traditionally-catholic countries.
AB  - The doctor's use of deception in appropriate circumstances has commonly been
      considered a necessity of the medical art. Resistance to full and frank
      communication is typical of many traditionally Catholic countries, and
      particularly of Italy, a western country where Catholicism remains particularly
      influential. The Catholic teaching on truth and lies, and the problem of telling
      the truth to a severely ill patient is discussed. It is suggested that the
      contemporary Catholic model of gradually telling a terminal patient the truth,
      which looks reasonable and feasible in theory, is rarely followed in practice, as
      in the majority of cases the truth is not told tout court. Problems stem from the
      way in which medicine is currently practiced in Italy; from the synergism between
      Catholicism and the medical tradition's grounded paternalism; and from the
      ambiguity of the term 'hope'. Catholic ethics in fact recommends that the truth
      must be told without destroying hope, but the Catholic meaning of 'hope' is very
      different from its meaning in current language.

PMID- 16423773
TI  - Bioethics in a global village.

PMID- 16423774
TI  - Don't be chicken: bioethics and avian flu.

PMID- 16423775
TI  - Informed consent revisited: Japan and the U.S.
AB  - Informed consent, decision-making styles and the role of patient-physician
      relationships are imperative aspects of clinical medicine worldwide. We present
      the case of a 74-year-old woman afflicted with advanced liver cancer whose
      attending physician, per request of the family, did not inform her of her true
      diagnosis. In our analysis, we explore the differences in informed-consent styles
      between patients who hold an "independent" and "interdependent" construal of the
      self and then highlight the possible implications maintained by this position in
      the context of international clinical ethics. Finally, we discuss the need to
      reassess informed-consent styles suitable to the needs of each patient regardless
      of whether he or she resides in the United States or in Japan.

PMID- 16423776
TI  - More information, broader dissent on informed consent.

PMID- 16423777
TI  - The family-facilitated approach could be dangerous if there is pressure by family
      dynamics.

PMID- 16423778
TI  - Culture and communication: medical disclosure in Japan and the U.S.

PMID- 16423779
TI  - Complications of culture in obtaining informed consent.

PMID- 16423780
TI  - Taking families seriously enough.

PMID- 16423781
TI  - Reconfiguring informed consent (with a little help from the capability approach).

PMID- 16423782
TI  - Informing consent: analogies to history-taking.

PMID- 16423783
TI  - Family and informed consent in multicultural setting.

PMID- 16423784
TI  - The doctor-patient relationship in the post-managed care era.
AB  - The growth of managed care was accompanied by concern about the impact that
      changes in health care organization would have on the doctor-patient relationship
      (DPR). We now are in a "post-managed care era," where some of these changes in
      health care delivery have come to pass while others have not. A re-examination of
      the DPR in this setting suggests some surprising results. Rather than posing a
      new and unprecedented threat, managed care was simply the most recent of numerous
      strains on the DPR that have occurred throughout the century. These strains are a
      constant, inevitable consequence of the varying needs and concerns of patient and
      physicians as they seek to balance their desires for a certain type of DPR with
      their simultaneous desire for other aspects of care such as lower costs, greater
      technological sophistication, and improved outcomes.

PMID- 16423785
TI  - Reinvesting in the doctor--patient relationship in the coming era of scarcity.

PMID- 16423786
TI  - Be clear about managed care to get clear about doctor-patient relations.

PMID- 16423787
TI  - What is managed care anyway?

PMID- 16423788
TI  - Family medicine, the physician-patient relationship, and patient-centered care.

PMID- 16423789
TI  - Finding meaning in the doctor-patient relationship.

PMID- 16423790
TI  - In search of medicine's moral glue.

PMID- 16423791
TI  - Quality of care in evaluating the doctor-patient relationship.

PMID- 16423792
TI  - Medical education, managed care and the doctor-patient relationship.

PMID- 16423793
TI  - If cardiologists take care of patients with heart disease, what do hospitalists
      treat?: hospitalists and the doctor-patient relationship.

PMID- 16423797
TI  - In vitro characterization of carbamazepine-loaded precifac lipospheres.
AB  - Lipospheres of carbamazepine were prepared by melt dispersion technique using
      Precifac ATO 5 in the various drug-lipid ratios. The resulting free-flowing
      lipospheres were evaluated with respect to surface morphology, particle size
      distribution, encapsulation efficiency, and in vitro release behavior. The effect
      of druglipid ratio, the surfactant added, emulsion stabilizer, and stirring speed
      also were identified as the key variables affecting the formation of discrete
      spherical lipospheres and drug release rate. The preparation conditions were
      optimized by using 0.4% w/v span 20 (Hydrophilic-Lipophilic Balance, HLB = 8.6)
      as a surfactant and 1% w/v gelatin solution as a stabilizer in presence of a high
      level of water. We found that the ratio of drug to lipid affects the size of the
      spheres. The incorporation efficiency was found to be high at all loadings.
      Increasing the lipid:drug ratio produced more spherical, smooth, and round
      lipospheres. All the prepared lipospheres exhibited slow release profiles
      dictating the Higuchi mode of release. We saw that the higher the sphere size and
      the ratio of Precifac, the slower is in vitro drug release.

PMID- 16423798
TI  - Preparation and characterization of poly(D,L-lactic-co-glycolic Acid)
      microspheres containing flurbiprofen sodium.
AB  - This study aimed to prepare biodegradable microspheres containing flurbiprofen
      sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery
      system to the periodontal pocket. Microspheres were prepared from biodegradable
      copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation
      method. The effects of the different copolymers and amounts of polyvinyl alcohol
      (PVA) as a dispersing agent on characteristics of the microspheres were
      evaluated. Although there was no correlation between microsphere size and amount
      of PVA, an optimum PVA concentration was essential to achieve narrower size
      distributions of microspheres. As the concentration of PVA increased, the drug
      loading of the microspheres increased. The effect of PVA on drug loading was
      found to be statistically significant for those microspheres prepared from PLGA
      50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher
      drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of
      microspheres (60-80%) were affected neither by different PVA concentrations nor
      by copolymer compositions (p > 0.05). According to the first-order release rate
      constants of the microspheres, the microspheres of PLGA 50:50 released the drug
      at the highest rate consistently, with the highest hydrophilicity of this
      copolymer.

PMID- 16423799
TI  - Use of natural gums and cellulose derivatives in production of sustained release
      metoprolol tablets.
AB  - Metoprolol tartrate sustained-release tablets (100 mg) were prepared using
      xanthan/guar gums and also hydroxypropyl methyl cellulose (HPMC) carboxymethyl
      Cellulose (CMC) polymers by direct compression method. Physical characteristics
      of the tablets and water uptake in addition to their dissolution profiles were
      compared with standard (Lopressor SR) tablets. Dissolution test was performed in
      the phosphate buffer solution (pH 6.8) and the samples were analyzed
      spectrophotometerically in 275.7 nm. Dissolution studies showed that formulations
      containing 100 and 80% of HPMC, 100% of guar, and 20% of xanthan followed the
      Higuchi model, while those containing 60 and 40% HPMC and 100 and 80% xanthan
      followed a zero-order model. The tablets with 40% xanthen followed a Hixon
      Crowell model. In cellulose derivatives the highest MDT and dissolution
      efficiency until 8 hr (DE8%) belonged to tablets with 40% HPMC, increasing the
      amount of CMC decreased the drug release rate, and formulations containing 60 and
      40% of HPMC had the USP dissolution standards. While, in the gum formulations,
      the highest mean dissolution time and the lowest DE(8)% belonged to tablets with
      100% xanthan, increasing the xanthan decreased the release rate of metoprolol,
      and formulations containing 80 and 100% xanthan had the USP dissolution
      standards. Results showed that natural gums are suitable for production of
      sustained-release tablets of metoprolol.

PMID- 16423800
TI  - Evaluation of polyvinyl acetate dispersion as a sustained release polymer for
      tablets.
AB  - Kollicoat SR 30D is a unique 30% aqueous dispersion of polyvinvyl acetate
      stabilized by polyvinyl-pyrrolidone intended for preparation of sustained release
      products. Detailed evaluation of this polymer dispersion as a sustained release
      coating for active pharmaceutical ingredients of two diverse classes of drugs was
      studied. A water insoluble drug (ibuprofen) and a water soluble drug (ascorbic
      acid) were selected as model active drugs. Ibuprofen was granulated using a GPCG
      1 fluid bed processor prior to tableting, to improve the particle size and
      particle flow properties. In this process a 2(3) factorial design was implemented
      to evaluate the optimum process parameters such as spray rate, inlet air
      temperature and the inlet air velocity. The statistical model selected was
      Y(ijkl) = mu + tau(i) + beta(j) + theta(k) + (taubeta)ij + (betatheta)jk +
      (tautheta)ik + (taubetatheta)ijk + epsilon(ijkl). The factorial design showed
      that the spray rate, inlet air temperature, and inlet air velocity had a
      significant effect (p value <0.05) on the particle size. Significant improvement
      was observed in the flow properties of the granules. The granules were coated
      with Kollicoat SR30D dispersion using top spray method in the fluid bed
      processor. The dissolution studies showed that the release of ibuprofen decreased
      with an increase in the coating levels of Kollicoat SR 30 D. In the case of
      ascorbic acid, preparation of sustained release coated commercial granules was
      not possible due to the difficulty in coating a highly soluble drug particle.
      However, the coated granules when compressed into tablets showed some
      sustainability. Ibuprofen tablets manufactured with coated granules with a 15 g
      polymer for 300 g batch showed dissolution parameters of t50 and t90 at 4.2 hr
      and 7.5 hr, respectively. An approximate zero-type of release was observed when
      the polymer content was increased to 45 g for 300 g batch. Ascorbic acid tablets
      made with coated commercial granules having a total polymer content of 45 g per a
      500 g batch showed an average dissolution t50 and t90 at 1.0 hr and 4.55 hr,
      respectively. When the total polymer content was increased to 60 g, per 500 g,
      the average dissolution t50 and t90 delayed to 1.40 hr and 7.20 hr, respectively.

PMID- 16423801
TI  - Pharmacodynamics of piroxicam from self-emulsifying lipospheres formulated with
      homolipids extracted from Capra hircus.
AB  - A self-emulsifying system is a mixture of oil and surfactant that forms oil-in
      water emulsion when exposed to aqueous fluid. It enhances the in vitro
      dissolution and improves the in vivo absorption of lipophilic drugs that have
      poor aqueous solubility. In this study, a poorly water soluble drug, piroxicam,
      was incorporated into self-emulsifying lipospheres consisting of a mixture of a
      homolipid from Capra hircus and Tween 65. Various solid self-emulsifying
      lipospheres were formulated having different ratios of the homolipid and Tween 65
      to contain piroxicam. The self-emulsifying lipospheres were evaluated using the
      following parameters: particle size, absolute drug content, and dissolution
      profile. The pharmacodynamics of the drug from the lipospheres were also
      evaluated using antinociceptive activity on albino mice. Based on our results the
      self-emulsifying lipospheres containing 4:11 ratio of the homolipid and Tween 65
      had the best performance in terms of antiinflammatory effect, particle size, and
      dissolution. They possibly could be employed in the formulation of self
      emulsifying lipospheres for various administration.

PMID- 16423802
TI  - Cross-linked guar gum hydrogel discs for colon-specific delivery of ibuprofen:
      formulation and in vitro evaluation.
AB  - Hydrogel discs of guar gum cross-linked with glutaraldehyde were prepared as
      vehicles for colon-specific drug delivery. Ibuprofen was chosen as model drug.
      The discs were evaluated for such parameters as size, shape, weight, and drug
      loading. Swelling (buffer uptake) and in vitro drug release study, in presence
      and absence of rat caecal contents, was performed in simulated gastric fluid (pH
      1.2) and simulated intestinal fluid (pH 7.4) to evaluate the effect of various
      formulation parameters like guar gum concentration, amount of cross-linking
      agent, and cross-linking time on drug release. Cross-linking resulted in
      significant reduction in swelling of guar gum. Significant increase in drug
      release was observed in medium containing rat caecal content. Percent drug
      release increased with increasing glutaraldehyde concentration. Cross-linking
      time and guar gum concentration did not have any significant effect on drug
      release in the range studied.

PMID- 16423803
TI  - Thermally reversible in situ gelling carbamazepine liquid suppository.
AB  - Carbamazepine (CBZ), indicated for the control of epilepsy, undergoes extensive
      hepatic first-pass elimination after oral administration. A rectal dosage form of
      CBZ is not commercially available, although it is of particular interest when
      oral administration is impossible. Conventional suppositories can cause patient
      discomfort and may reach the end of the colon; consequently, the drug can undergo
      the first-pass effect. Mucoadhesive liquid suppositories of CBZ were prepared by
      adding carbopol to formulation of thermally gelling suppositories that contain
      20% poloxamer 407 and either 15% poloxamer 188 or 1% methylcellulose. Gellan gum
      was also tried instead of 20% poloxamer. All formulations contained 10% CBZ. The
      characteristics of the suppositories differed depending on the formulation. The
      formula containing 20% poloxamer 407, 1% methylcellulose, and 0.5% carbopol
      showed reasonable gelation temperature, gel strength and bioadhesive force. The
      analysis of release mechanism showed that CBZ released from the suppositories by
      Fickian diffusion. In vivo evaluation of the same formulation showed higher peak
      plasma concentration of CBZ compared with the orally administered suspension
      containing the equivalent amount of drug. However, there was no statistical
      significant difference (p > 0.05) in extent of bioavailability between the liquid
      suppository and oral suspension as indicated by the values of AUC(0 - infinity),
      17.9 and 18.8 micro g x h/ml, respectively. These results suggested that
      mucoadhesive in situ gelling liquid suppository could be an effective and
      convenient delivery system of carbamazepine.

PMID- 16423804
TI  - Administration of optimum sustained-insulin release PLGA microcapsules to
      spontaneous diabetes-prone BB/Wor//Tky rats.
AB  - To show the possibility of sustained-release insulin formulation composed of
      PLGA, the optimum one was administered to BioBreeding rat, a model of spontaneous
      type I diabetes mellitus (IDDM). Every 2 weeks subcutaneous administration made
      their blood glucose level depend on the insulin release and food intake. However,
      all of them kept alive with little change or rather a little gain in body weight.
      Furthermore, some of pregnant rats with intermittent treatment bore fetuses,
      although additional insulin therapy seemed necessary. Therefore, the formulation
      could become a new tool as a provider of basal insulin for IDDM patients.

PMID- 16423805
TI  - A new bioimaging carrier for fluorescent quantum dots: phospholipid nanoemulsion
      mimicking natural lipoprotein core.
AB  - Fluorescent quantum dots (semiconductor nanocrystals) have the potential to
      revolutionize biological imaging, but their use has been limited by difficulties
      in obtaining quantum dots that are water soluble and biocompatible. The
      objectives of our research were to develop a methodology for encapsulation of
      cadnium-selenium (CdSe) quantum dots (QDs) in phospholipid nanoemulsion that
      mimics the natural lipoprotein core and to study their interactions with cultured
      non-small cell lung cancer cells (NSCLC). We found that CdSe QDs can be
      efficiently encapsulated in the phospholipid nanoemulsion. The QD nanoemulsion
      has a particle size approximately 80 nm and appears physically stable. The QD
      nanoemulsion interacts well with cells. The intensity of cellular fluorescence
      imaging increases with the cell incubation time, indicating more QDs were taken
      up by the cells, respectively. Two types of fluorescence microscopies confirm
      that QDs are primarily localized in the cytoplasm but not in the nucleus of the
      cells.

PMID- 16423808
TI  - Isocyanate exposure in an autobody repair and collision center.

PMID- 16423809
TI  - Airborne hexamethylene diisocyanate and particulate matter exposures during
      fire/rescue vehicle ladder finishing operations.

PMID- 16423810
TI  - Parathyroid hormone: past and present.
AB  - Research on parathyroid hormone (PTH) has undergone four rather distinctive
      phases, beginning just before the turn of the 20th century. Early debates about
      the function of the parathyroids were resolved by 1925, when understanding the
      role of PTH led to comprehending the action of the glands in calcium physiology.
      Elucidation of the pathophysiology of hormone excess (severe bone loss) and
      deficiency (hypocalcemia) continued over the following decades. With the advent
      of advances in chemical and molecular biology, the structure of PTH and its
      principal receptor (PTHrP-receptor [PTHR1]) were established. Tests with purified
      hormonal peptide in humans led to the surprising, even paradoxical, finding that
      PTH can be used pharmacologically to build bone, providing a dramatic therapeutic
      impact on osteoporosis. These developments have stimulated the field of calcium
      and bone biology and posed new questions about the role of PTH as well as
      possible new directions in therapy.

PMID- 16423811
TI  - MicroRNAs and endocrine biology.
AB  - microRNAs (miRNAs) are highly conserved, non-coding RNAs that powerfully regulate
      gene expression at the post-transcriptional level. These fascinating molecules
      play essential roles in many biological processes in mammals, including insulin
      secretion, B-cell development, and adipocyte differentiation. This review
      provides a general background regarding current knowledge about miRNA biogenesis
      and the potential contributions of these RNAs to endocrine function.

PMID- 16423812
TI  - Hormonology: a genomic perspective on hormonal research.
AB  - Recent advances in comparative genomics allow a new paradigm for hormonal
      research. At the centennial of the first use of the term hormone by Ernest
      Starling, we reflected on the changing approaches in elucidating hormonal
      signaling mechanisms and highlighted the inadequacy of the term endocrinology,
      implying remote activation, to describe the diverse modes of hormone actions.
      Several examples were presented to underscore the power of comparative genomics
      in the identification of new polypeptide hormones, receptors, and signaling
      pathways. We propose the use of the term hormonology to more accurately reflect
      the expanding boundaries of the discipline.

PMID- 16423813
TI  - Change in prostaglandin E synthases (PGESs) in microsomal PGES-1 knockout mice in
      a preterm delivery model.
AB  - Most preterm deliveries are associated with infection and inflammation.
      Prostaglandin E2 (PGE2) is one of the most important mediators in the processes
      of inflammation, and is converted from PGH2 by various kinds of PGE synthases
      (PGESs). Among PGESs, microsomal PGES-1 (mPGES-1) is known to be the most
      important subtype in the processes of inflammation. To evaluate the role of PGESs
      in preterm delivery, we used mPGES-1 knockout mice in a lipopolysaccharide (LPS)
      induced preterm labor model. Unexpectedly, the duration of labor after LPS
      treatment was not statistically different between C57BL6 wild-type mice and mPGES
      1 knockout mice. In wild-type mice, mPGES-1 mRNA and protein expression increased
      in the myometrium and fetal membrane after LPS treatment. In contrast, the
      expression of mPGES-2 or cytosolic PGES was not changed by LPS treatment. On
      mPGES-1 knockout mice, mPGES-2 increased by LPS treatment in myometrium. The
      present data indicate that mPGES-1 may be involved in LPS-induced preterm labor,
      but inhibition of mPGES-1 alone may not prevent preterm delivery, because mPGES-2
      might compensate for the role of mPGES-1.

PMID- 16423814
TI  - Endocrine roles of D-aspartic acid in the testis of lizard Podarcis s. sicula.
AB  - In the lizard Podarcis s. sicula, a substantial amount of D-aspartate (D-Asp) is
      endogenous to the testis and shows cyclic changes of activity connected with sex
      hormone profiles during the annual reproductive phases. Testicular D-Asp content
      shows a direct correlation with testosterone titres and a reverse correlation
      with 17beta-estradiol titres. In vivo experiments, consisting of i.p. injections
      of 2.0 micromol/g body weight of D-Asp or other amino acids, in lizards collected
      during the three main phases of the reproductive cycle (pre-reproductive,
      reproductive and post-reproductive period), revealed that the testis can
      specifically take up and accumulate D-Asp alone. Moreover, this amino acid
      influences the synthesis of testosterone and 17beta-estradiol in all phases of
      the cycle. This phenomenon is particularly evident during the pre- and post
      reproductive period, when endogenous testosterone levels observed in both testis
      and plasma were the lowest and 17beta-estradiol concentrations were the highest.
      D-Asp rapidly induces a fall in 17beta-estradiol and a rise in testosterone at 3
      h post-injection in the testis and at 6 h post-injection in the blood. In vitro
      experiments show that testicular tissue converted L-Asp into D-Asp through an
      aspartate racemase. D-Asp synthesis was measured in all phases of the cycle, but
      was significantly higher during the reproductive period with a peak at pH 6.0.
      The exogenous D-Asp also induces a significant increase in the mitotic activity
      of the testis at 3 h (P < 0.05) and at 6 h (P < 0.01). Induction of
      spermatogenesis by D-Asp is recognized by an intense immunoreactivity of the
      germinal epithelium (spermatogonia and spermatids) for proliferation cell nuclear
      antigen (PCNA). The effects of D-Asp on the testis appear to be specific since
      they were not seen in lizards injected with other D- or L-forms of amino acids
      with known excitatory effects on neurosecretion. Our results suggest a regulatory
      role for D-Asp in the steroido-genesis and spermatogenesis of the testis of the
      lizard Podarcis s. sicula.

PMID- 16423815
TI  - Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann
      syndrome and normosmic hypogonadotropic hypogonadism patients.
AB  - We report the results of molecular analysis in a series of twelve Kallmann
      syndrome (KS) and five normosmic hypogonadotropic hypogonadism (nHH) Brazilian
      patients. Kallman syndrome 1 (KAL-1) gene analysis was performed in all patients
      and the gonadotrophin releasing hormone receptor (GnRH-R) gene was investigated
      in nHH patients using PCR analysis with exon-flanking primers followed by
      automated sequencing techniques. Two-point mutations at the KAL-1 locus were
      found in two KS patients. One case exhibited a novel C deletion (del1956C) in
      exon 12 leading to a premature stop codon at position 617. The second case, a C
      to T transition at exon 5, showed a stop codon at aminoacid 191 (Arg191X). Renal
      agenesis and bimanual synkinesis, which are frequently found in patients with the
      KAL-1 mutation, were observed in these cases. Among the KS patients, two
      previously reported cases had intragenic deletions of exons 5-10, while a third
      patient had a KAL-1 gene microdeletion detected by fluorescence in situ
      hybridization. For the nHH patients, no abnormalities were observed at the exonic
      and flanking sequences of the KAL-1 or GnRH-R genes. Nasal embryonic LHRH factor
      (NELF) and early B-cell factor 2 (EBF2) exons were evaluated in KAL-1/GnRH-R
      mutation-negative cases (seven KS and five nHH) by sequence analysis but no
      mutations were identified in the coding regions in these patients. In conclusion,
      this report includes the description of a novel point mutation of the KAL-1 gene
      and suggests that the KAL-1 mutations and deletions might be more prevalent in KS
      Brazilian patients than previously described in other series. NELF and EBF2 genes
      have been considered good candidates for HH and a large number of patients need
      to be studied to assess their contribution to reproductive function.

PMID- 16423816
TI  - Effects of decreased estradiol-17beta on the serum and anterior pituitary IGF-I
      system in pigs.
AB  - To further delineate the role of estradiol in the IGF system an experiment was
      conducted to determine the dosage of the aromatase inhibitor, anastrozole, needed
      to decreases serum concentrations of estradiol-17beta (E2) in maturing boars. A
      second experiment was conducted to determine if administration of anastrozole to
      growing boars decreased serum concentrations of E2 and affected components of the
      serum and anterior pituitary gland (AP) IGF system vs untreated boars and
      barrows. In Experiment 1, 12 crossbred boars (292 days, 158 kg) were administered
      either 0, 1 or 10 mg/day anastrozole (n = 4/group) beginning on day 1. Blood
      samples were collected every 7-14 days. Mean serum concentrations of E2 were
      decreased (P < 0.05) in the 10 mg group vs the 0 and 1 mg groups by day 36;
      however, no difference (P > 0.05) existed between the 0 and 1 mg groups. In
      Experiment 2, 24 crossbred boars and 12 barrows (101 days, 44 kg) were stratified
      by litter to one of three treatment groups (n = 12): boars administered 10 mg/day
      anastrozole, boars administered 0 mg/day, and barrows administered 0 mg/day.
      Blood samples were collected and pigs were weighed on day 0 and every 14 days
      thereafter, then killed on day 84 when blood and APs were collected. The 10
      mg/day pigs were fed the anastrozole-amended diet beginning on day 1. Mean serum
      concentrations of E2 did not differ (P > 0.05) between the 10 mg/day pigs and 0
      mg/day pigs on day 0; however, on day 15 through to 84 mean serum concentrations
      of E2 were greater (P < 0.05) in 0 mg/day pigs than in the 10 mg/day pigs. Mean
      percentage increase in serum concentrations of IGF-I was greater (P < 0.05) in
      untreated boars than anastrozole-treated boars and barrows from day 58 through to
      84. Mean percentage of basal IGF-I increased (P < 0.05) from day 29 through to 84
      in untreated boars. Mean relative amounts of AP IGF-binding protein (IGFBP)-2 and
      -5 were less (P < 0.01) in 10 mg/day pigs than in the 0 mg/day pigs, but each was
      greater (P < 0.01) than in barrows administered 0 mg/day. These results indicate
      anastrozole administered at a dosage of 10 mg/day suppresses serum concentrations
      of E2 in pigs. Administration of anastrozole to boars reduced the percentage
      increase in serum concentrations of IGF-I and relative amounts of AP IGFBP-2 and 
      5. These data further support a role for E2 in regulating components of the IGF
      system in pigs.

PMID- 16423817
TI  - Somatostatin receptor subtype expression in the human heart: differential
      expression by myocytes and fibroblasts.
AB  - In acromegaly, somatostatin receptor ligands (SRLs) can ameliorate left
      ventricular hypertrophy (LVH) and their use is associated with demonstrable
      improvements in various parameters of cardiac function. It remains unclear as to
      whether these beneficial effects are principally attributable to falling GH and
      IGF-I levels, or whether SRLs exert independent direct effects on the heart via
      somatostatin receptors. To help address this issue, we have sought to investigate
      somatostatin receptor expression in human heart. A human heart cDNA library was
      probed using PCR techniques to determine expression of somatostatin receptor
      subtypes. Subsequently, human heart biopsies and human cardiac fibroblasts and
      myocytes were analysed to determine whether expression differed between cardiac
      chambers or cell types. mRNAs for four of the five somatostatin receptor subtypes
      (sst1, sst2, sst4 and sst5) were shown to be co-expressed by the human heart.
      These receptors were present in both atrial and ventricular tissue. Human cardiac
      myocytes expressed mRNA for only sst1 and sst2, while human cardiac fibroblasts
      expressed all four subtypes found in whole heart tissue. The expression of
      functional somatostatin receptors on human cardiac fibroblasts was confirmed by
      mobilisation of intracellular calcium in response to somatostatin. The presence
      of cardiac somatostatin receptors raises the possibility of a direct effect of
      somatostatin analogues on the heart. Furthermore, the differential expression of
      somatostatin receptor subtypes by human cardiac myocytes and fibroblasts opens up
      the possibility of differential modulation of the cell types in the heart by
      subtype-specific somatostatin analogues.

PMID- 16423818
TI  - Increased sensitivity to GH in liver of Ames dwarf (Prop1df/Prop1df) mice related
      to diminished CIS abundance.
AB  - To investigate the influence of chronic GH deficiency on GH signaling in vivo, we
      have analyzed Janus kinase (JAK) 2/signal transducers and activators of
      transcription (STAT) 5 GH signaling pathway, and its regulation by the
      suppressors of the cytokine signaling SOCS and by the JAK2-interacting protein
      SH2-Bbeta, in liver of Ames dwarf (Prop1df/Prop1df) mice, which are severely
      deficient in GH, prolactin and TSH, and of their normal littermates.
      Prop1df/Prop1df mice displayed unaltered GH receptor, JAK2 and STAT5a/b protein
      levels. No significant differences in the basal tyrosine-phosphorylation levels
      of JAK2 and STAT5a/b were found between both groups of animals. After in vivo
      administration of a high GH dose (5 microg/g body weight (BW)), the tyrosine
      phosphorylation levels of JAK2 and STAT5a/b increased significantly, reaching
      similar values in normal and dwarf mice. However, after stimulation with lower GH
      doses (50 and 15 ng/g BW) the tyrosine-phosphorylation level of STAT5a/b was
      higher in dwarf mice. The protein content of CIS, a SOCS protein that inhibits
      STAT5 signaling, was approximately 80% lower in dwarf mice liver, while SOCS-2
      and SOCS-3 levels were unaltered. The content of SH2-Bbeta, a modulator of JAK2
      activity, was reduced by approximately 30% in dwarf mice, although this was
      associated with normal JAK2 response to a high GH dose. In summary,
      Prop1df/Prop1df mice display increased hepatic sensitivity to GH, an effect that
      could be related to the lower abundance of CIS in this tissue. Furthermore, the
      lower CIS content found in this model of GH deficiency suggests that CIS protein
      levels are regulated by GH in vivo.

PMID- 16423819
TI  - Ghrelin against alendronate-induced gastric damage in rats.
AB  - Alendronate sodium, a primary amino bisphosphonate, is widely used in the
      treatment of various diseases that are associated with bone resorption, such as
      postmenopausal osteoporosis and Paget's disease of bone. Although the adverse
      effects of biphosphonates on the gastrointestinal system have been demonstrated
      in experimental and clinical studies, the exact mechanisms underlying this damage
      are not clear yet. Ghrelin, a 28 amino acid peptide produced predominantly by the
      stomach, was shown to exert a potent protective action on the stomach of rats
      exposed to ethanol or stress. Our objective was to evaluate the possible anti
      oxidant and anti-inflammatory effects of ghrelin against alendronate-induced
      gastric damage. Wistar albino rats were administered alendronate (20 mg/kg) by
      gavage for 4 days, along with either ghrelin (10 ng/kg per day) or saline given
      i.p. After decapitation, stomach tissues were removed for the determination of
      malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO)
      activity and tissue collagen content, while the extent of tissue damage was
      analyzed microscopically. Formation of reactive oxygen species was determined by
      chemiluminesence using a luminol probe in fresh gastric tissues. Serum tumor
      necrosis factor (TNF-alpha) and lactate dehydrogenase levels were assessed in
      trunk blood. Oral administration of alendronate-induced significant gastric
      damage, accompanied by increased MPO activity, collagen content, MDA and luminol
      levels (P < 0.01-P < 0.001), while tissue GSH was decreased (P < 0.01). On the
      other hand, ghrelin treatment reversed these alterations (P < 0.05-P < 0.001) as
      well as elevating serum TNF-alpha levels significantly (P < 0.001). The findings
      of the present study suggest that alendronate induces oxidative gastric damage by
      a local irritant effect, and ghrelin ameliorates this damage by its possible
      antioxidant and anti-inflammatory properties.

PMID- 16423820
TI  - Altered Glut-2 accumulation and beta-cell function in mice lacking the exocrine
      specific transcription factor, Mist1.
AB  - Mist1 is an exocrine-specific transcription factor that is necessary for the
      establishment of cell organization and function of pancreatic acinar cells. While
      Mist1 is not expressed in the endocrine pancreas, the disorganized phenotype of
      the exocrine component may affect endocrine function. Therefore, we examined
      endocrine tissue morphology and function in Mist1-knockout (Mist1(KO)) mice.
      Endocrine function was evaluated using a glucose-tolerance test on 2-10-month-old
      female mice and revealed a significant reduction in glucose-clearing ability in
      10-month-old Mist1(KO) mice compared with wild-type mice. Immunohistochemical
      analysis of islet hormone expression indicated that the decreased endocrine
      function was not due to a decrease in insulin-, glucagon- or somatostatin
      expressing cells. However, a decrease in the size of islets in 10-month-old
      Mist1(KO) mice was observed along with a decrease in Glut-2 protein accumulation.
      These results suggest that the islets in Mist1(KO) mice are functionally
      compromised, likely accounting for the decreased glucose tolerance. Based on
      these findings, we have identified that the loss of a regulatory gene in the
      exocrine compartment can affect the endocrine component, providing a possible
      link between susceptibility for various pancreatic diseases.

PMID- 16423822
TI  - Asymmetric cooperativity in a symmetric tetramer: human hemoglobin.

PMID- 16423821
TI  - Exogenous expression of glucagon-like peptide 1 receptor and human insulin in AtT
      20 corticotrophs confers cAMP-mediated gene transcription and insulin secretion.
AB  - The insulinotrophic effects of glucagon-like peptide 1 (GLP-1) are mediated by
      its seven-transmembrane receptor (GLP-1R) in pancreatic beta-cells. We have
      transiently transfected the GLP-1R and a proopiomelanocortin (POMC) promoter
      driven human preproinsulin gene vector (pIRES) into the AtT-20 pituitary
      corticotrophic cell line, to investigate the possibility of creating a regulated,
      insulin-expressing cell line. Receptor expression was confirmed by RT-PCR and
      functionality was demonstrated by measuring changes in cAMP levels in response to
      GLP-1. Rapid (5 min) stimulation of cAMP production was observed with 100 nM GLP
      1, 24 h after transfection of 2 microg GLP-1R DNA. AtT-20 cells co-transfected
      with GLP-1R and human glycoprotein hormone alpha-subunit or rat POMC promoters
      revealed GLP-1-stimulated cAMP activation of transcription. Co-transfection of
      the pIRES vector with the GLP-1R resulted in GLP-1-stimulated activation of POMC
      promoter-driven preproinsulin gene transcription but insulin secretion was not
      detected. However, using an adenoviral expression system to infect AtT-20 cells
      with GLP-1R and the preproinsulin gene (including 120 bp of its own promoter)
      resulted in a 6.4 +/- 0.6-fold increase in cAMP and a 4.9 +/- 0.8-fold increase
      in insulin secretion in response to 100 nM GLP-1. These results demonstrate, for
      the first time, functional GLP-1R-mediated preproinsulin gene transcription and
      secretion in a transplantable cell line.

PMID- 16423823
TI  - Catalytic mechanism of class B2 metallo-beta-lactamase.
AB  - The initial nucleophilic substitution step of biapenem hydrolysis catalyzed by a
      subclass B2 metallo-beta-lactamase (CphA from Aeromonas hydrophila) is
      investigated using hybrid quantum mechanical/molecular mechanical methods and
      density functional theory. We focused on a recently proposed catalytic mechanism
      that involves a non-metal-binding water nucleophile in the active site of the
      monozinc CphA. Both theoretical models identified a single transition state
      featuring nearly concomitant nucleophilic addition and elimination steps, and the
      activation free energy from the potential of mean force calculations was
      estimated to be approximately 14 kcal/mol. The theoretical results also
      identified the general base for activating the water nucleophile to be the metal
      binding Asp-120 rather than His-118, as suggested earlier. The protonation of Asp
      120 leads to cleavage of the O(delta2)-Zn coordination bond, whereas the
      negatively charged nitrogen leaving group resulting from the ring opening
      replaces Asp-120 as the fourth ligand of the sole zinc ion. The electrophilic
      catalysis by the metal ion provides sufficient stabilization for the leaving
      group to avoid a tetrahedral intermediate. The theoretical studies provided
      detailed insights into the catalytic strategy of this unique metallo-beta
      lactamase.

PMID- 16423824
TI  - Delta-subunit confers novel biophysical features to alpha beta gamma-human
      epithelial sodium channel (ENaC) via a physical interaction.
AB  - Native amiloride-sensitive Na+ channels exhibit a variety of biophysical
      properties, including variable sensitivities to amiloride, different ion
      selectivities, and diverse unitary conductances. The molecular basis of these
      differences has not been elucidated. We tested the hypothesis that co-expression
      of delta-epithelial sodium channel (ENaC) underlies, at least in part, the
      multiplicity of amiloride-sensitive Na+ conductances in epithelial cells. For
      example, the delta-subunit may form multimeric channels with alpha beta gamma
      ENaC. Reverse transcription-PCR revealed that delta-ENaC is co-expressed with
      alpha beta gamma-subunits in cultured human lung (H441 and A549), pancreatic
      (CFPAC), and colonic epithelial cells (Caco-2). Indirect immunofluorescence
      microscopy revealed that delta-ENaC is co-expressed with alpha-, beta-, and gamma
      ENaC in H441 cells at the protein level. Measurement of current-voltage that
      cation selectivity ratios for the revealed relationships
      Na+/Li+/K+/Cs+/Ca2+/Mg2+, the apparent dissociation constant (Ki) for amiloride,
      and unitary conductances for delta alpha beta gamma-ENaC differed from those of
      both alpha beta gamma- and delta beta gamma-ENaC (n = 6). The contribution of the
      delta subunit to P(Li)/P(Na) ratio and unitary Na+ conductance under bi-ionic
      conditions depended on the injected cRNA concentration. In addition, the EC50 for
      proton activation, mean open and closed times, and the self-inhibition time of
      delta alpha beta gamma-ENaC differed from those of alpha beta gamma- and delta
      beta gamma-ENaC. Co-immunoprecipitation of delta-ENaC with alpha- and gamma
      subunits in H441 and transfected COS-7 cells suggests an interaction among these
      proteins. We, therefore, concluded that the interactions of delta-ENaC with other
      subunits could account for heterogeneity of native epithelial channels.

PMID- 16423825
TI  - HIV-1 Tat is a natively unfolded protein: the solution conformation and dynamics
      of reduced HIV-1 Tat-(1-72) by NMR spectroscopy.
AB  - Tat (transactivator of transcription) is a small RNA-binding protein that plays a
      central role in the regulation of human immunodeficiency virus type 1 replication
      and in approaches to treating latently infected cells. Its interactions with a
      wide variety of both intracellular and extracellular molecules is well
      documented. A molecular understanding of the multitude of Tat activities requires
      a determination of its structure and interactions with cellular and viral
      partners. To increase the dispersion of NMR signals and permit dynamics analysis
      by multinuclear NMR spectroscopy, we have prepared uniformly 15N- and 15N/13C
      labeled Tat-(1-72) protein. The cysteine-rich protein is unambiguously reduced at
      pH 4.1, and NMR chemical shifts and coupling constants suggest that it exists in
      a random coil conformation. Line broadening and multiple peaks in the Cys-rich
      and core regions suggest that transient folding occurs in two of the five
      sequence domains. NMR relaxation parameters were measured and analyzed by
      spectral density and Lipari-Szabo approaches, both confirming the lack of
      structure throughout the length of the molecule. The absence of a fixed
      conformation and the observation of fast dynamics are consistent with the ability
      of Tat protein to interact with a wide variety of proteins and nucleic acid and
      support the concept of a natively unfolded protein.

PMID- 16423826
TI  - Defective one- or two-electron reduction of the anticancer anthracycline
      epirubicin in human heart. Relative importance of vesicular sequestration and
      impaired efficiency of electron addition.
AB  - One-electron quinone reduction and two-electron carbonyl reduction convert the
      anticancer anthracycline doxorubicin to reactive oxygen species (ROS) or a
      secondary alcohol metabolite that contributes to inducing a severe form of
      cardiotoxicity. The closely related analogue epirubicin induces less
      cardiotoxicity, but the determinants of its different behavior have not been
      elucidated. We developed a translational model of the human heart and
      characterized whether epirubicin exhibited a defective conversion to ROS and
      secondary alcohol metabolites. Small myocardial samples from cardiac surgery
      patients were reconstituted in plasma that contained clinically relevant
      concentrations of doxorubicin or epirubicin. In this model only doxorubicin
      formed ROS, as detected by fluorescent probes or aconitase inactivation.
      Experiments with cell-free systems and confocal laser scanning microscopy studies
      of H9c2 cardiomyocytes suggested that epirubicin could not form ROS because of
      its protonation-dependent sequestration in cytoplasmic acidic organelles and the
      consequent limited localization to mitochondrial one-electron quinone reductases.
      Accordingly, blocking the protonation-sequestration mechanism with the vacuolar
      H+-ATPase inhibitor bafilomycin A1 relocalized epirubicin to mitochondria and
      increased its conversion to ROS in human myocardial samples. Epirubicin also
      formed approximately 60% less alcohol metabolites than doxorubicin, but this was
      caused primarily by its higher Km and lower Vmax values for two-electron carbonyl
      reduction by aldo/keto-reductases of human cardiac cytosol. Thus, vesicular
      sequestration and impaired efficiency of electron addition have separate roles in
      determining a defective bioactivation of epirubicin to ROS or secondary alcohol
      metabolites in the human heart. These results uncover the molecular determinants
      of the reduced cardiotoxicity of epirubicin and serve mechanism-based guidelines
      to improving antitumor therapies.

PMID- 16423827
TI  - Endothelin-3-converting enzyme activity of the KEL1 and KEL6 phenotypes of the
      Kell blood group system.
AB  - The Kell blood group protein is a metalloendopeptidase that preferentially
      cleaves a Trp(21)-Ile(22) bond of big endothelin-3 producing bioactive endothelin
      3. Kell is a polymorphic protein, and 25 different phenotypes, because of point
      mutations resulting in single amino acid substitutions, have been described. It
      was recently reported that a recombinant form of KEL1 (K, K1) phenotype,
      expressed in K562 and HEK293 cells, had no endothelin-3-converting activity, in
      contrast to the common KEL2 (k, K2) phenotype. We demonstrate that KEL1 red blood
      cells and also a soluble recombinant form of KEL1 protein (s-Kell KEL1) have
      similar enzymatic activity as the common Kell phenotype. In addition we show that
      KEL6 red blood cells, which are more prevalent in persons of African heritage
      than in Caucasians also have endothelin-3-converting enzyme activity and that the
      recombinant soluble form of KEL6 protein (s-Kell KEL6) has similar K(m) values as
      the wild-type.

PMID- 16423829
TI  - Saccharomyces cerevisiae lacking Btn1p modulate vacuolar ATPase activity to
      regulate pH imbalance in the vacuole.
AB  - The vacuolar H(+)-ATPase (V-ATPase) along with ion channels and transporters
      maintains vacuolar pH. V-ATPase ATP hydrolysis is coupled with proton transport
      and establishes an electrochemical gradient between the cytosol and vacuolar
      lumen for coupled transport of metabolites. Btn1p, the yeast homolog to human
      CLN3 that is defective in Batten disease, localizes to the vacuole. We previously
      reported that Btn1p is required for vacuolar pH maintenance and ATP-dependent
      vacuolar arginine transport. We report that extracellular pH alters both V-ATPase
      activity and proton transport into the vacuole of wild-type Saccharomyces
      cerevisiae. V-ATPase activity is modulated through the assembly and disassembly
      of the V(0) and V(1) V-ATPase subunits located in the vacuolar membrane and on
      the cytosolic side of the vacuolar membrane, respectively. V-ATPase assembly is
      increased in yeast cells grown in high extracellular pH. In addition, at elevated
      extracellular pH, S. cerevisiae lacking BTN1 (btn1-Delta), have decreased V
      ATPase activity while proton transport into the vacuole remains similar to that
      for wild type. Thus, coupling of V-ATPase activity and proton transport in btn1
      Delta is altered. We show that down-regulation of V-ATPase activity compensates
      the vacuolar pH imbalance for btn1-Delta at early growth phases. We therefore
      propose that Btn1p is required for tight regulation of vacuolar pH to maintain
      the vacuolar luminal content and optimal activity of this organelle and that
      disruption in Btn1p function leads to a modulation of V-ATPase activity to
      maintain cellular pH homeostasis and vacuolar luminal content.

PMID- 16423828
TI  - Structural determinants of slippage-mediated mutations by human immunodeficiency
      virus type 1 reverse transcriptase.
AB  - Single-base deletions at nucleotide runs or -1 frameshifting by human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) result from
      template slippage during polymerization. In crystal structures of HIV-1 RT
      complexed with DNA-DNA template-primer, the palm subdomain in the template cleft
      contacts the template backbone near the proposed site of slippage via the Glu(89)
      side chain. We investigated the role of Glu(89) in frameshifting by perturbing
      this interaction. Substitutions with Asp, Gly, Ala, Val, Ser, Thr, Asn, or Lys
      were created in recombinant HIV RT, and frameshift frequencies of the resulting
      mutant RTs were measured. All substitutions led to reduced -1 frameshifting by
      HIV-1 RT (2-40-fold). Interestingly, the suppression of -1 frameshifting
      frequently coincided with an enhancement of +1 frameshifting (3-47-fold)
      suggesting that Glu(89) can influence the slippage of both strands. Glu(89)
      substitutions also led to reduced rates of dNTP misincorporation that paralleled
      reductions in -1 frameshifting, suggesting a common structural mechanism for both
      classes of RT error. Our results reveal a major influence of Glu(89) on slippage
      mediated errors and dNTP incorporation fidelity. The crystal structure of HIV-1
      RT reveals a salt bridge between Glu(89) and Lys(154), which may facilitate -1
      frameshifting; this concept is supported by the observed reduction in -1
      frameshifting for K154A and K154R mutants.

PMID- 16423830
TI  - Leishmania major expresses a single dihydroxyacetone phosphate acyltransferase
      localized in the glycosome, important for rapid growth and survival at high cell
      density and essential for virulence.
AB  - Despite major advances in the understanding of pathogenesis of the human
      protozoan parasite Leishmania major, little is known about the enzymes and the
      primary precursors involved in the initial steps of synthesis of its major
      glycerolipids including those involved in virulence. We have previously
      demonstrated that the initial step of acylation of the precursor glycerol 3
      phosphate is not essential for the synthesis of ester and ether phospholipids in
      this parasite. Here we show that Leishmania expresses a single acyltransferase
      with high specificity for the precursor dihydroxyacetone phosphate and shows the
      best activity in the presence of palmitoyl-CoA. We have identified and
      characterized the LmDAT gene encoding this activity. LmDAT complements the
      lethality resulting from the loss of both dihydroxyacetone phosphate and glycerol
      3-phosphate acyltransferase activities in yeast. Recombinant LmDAT exhibits
      biochemical properties similar to those of the native enzyme of the promastigote
      stage parasites. We show that LmDAT is a glycosomal enzyme and its loss in a
      delta lmdat/delta lmdat null mutant results in complete abrogation of the
      parasite dihydroxyacetone phosphate acyltransferase activity. Furthermore, lack
      of LmDAT causes a major alteration in parasite division during the logarithmic
      phase of growth, an accelerated cell death during stationary phase, and loss of
      virulence. Together, our results demonstrate that LmDAT is the only
      dihydroxyacetone phosphate acyltransferase of the L. major localized in the
      peroxisome, important for growth and survival and essential for virulence.

PMID- 16423831
TI  - Involvement of the Ras-Ras-activated Rab5 guanine nucleotide exchange factor RIN2
      Rab5 pathway in the hepatocyte growth factor-induced endocytosis of E-cadherin.
AB  - E-cadherin is a key cell-cell adhesion molecule at adherens junctions (AJs) and
      undergoes endocytosis when AJs are disrupted by the action of an extracellular
      signal, such as hepatocyte growth factor (HGF)/scatter factor. Rab5 small G
      protein has been implicated in the HGF-induced endocytosis of E-cadherin, but the
      molecular mechanism for the regulation of Rab5 activity remains unknown. We first
      studied this mechanism by using the cell-free assay system for the endocytosis of
      E-cadherin of the AJ-enriched fraction from rat livers. HGF induced activation of
      Ras small G protein, which then bound to RIN2, a Rab5 GDP/GTP exchange factor
      with the Vps9p-like guanine nucleotide exchange factor and Ras association
      domains, and activated it. Activated RIN2 then activated Rab5, eventually
      inducing the endocytosis of E-cadherin. We then studied whether RIN2 was involved
      in the HGF-induced endocytosis of E-cadherin in intact Madin-Darby canine kidney
      cells. RIN2 localized at the cell-cell adhesion sites, and its guanine nucleotide
      exchange factor activity was required for the HGF-induced endocytosis of E
      cadherin in Madin-Darby canine kidney cells. These results indicate that RIN2
      connects Ras to Rab5 in the HGF-induced endocytosis of E-cadherin.

PMID- 16423833
TI  - Identification of a polymeric Ig receptor binding phage-displayed peptide that
      exploits epithelial transcytosis without dimeric IgA competition.
AB  - The polymeric Ig receptor (pIgR), also called membrane secretory component (SC),
      mediates epithelial transcytosis of polymeric immunoglobulins (pIgs). J Chain
      containing polymeric IgA (pIgA) and pentameric IgM bind pIgR at the basolateral
      epithelial surface. After transcytosis, the extracellular portion of the pIgR is
      cleaved at the apical side, either complexed with pIgs as bound SC or unoccupied
      as free SC. This transport pathway may be exploited to target bioactive molecules
      to the mucosal surface. To identify small peptide motifs with specific affinity
      to human pIgR, we used purified free SC and selection from randomized, cysteine
      flanked 6- and 9-mer phage-display libraries. One of the selected phages, called
      C9A, displaying the peptide CVVWMGFQQVC, showed binding both to human free SC and
      SC complexed with pIgs. However, the pneumococcal surface protein SpsA
      (Streptococcus pneumoniae secretory IgA-binding protein), which binds human SC at
      a site distinct from the pIg binding site, competed with the C9A phage for
      binding to SC. The C9A phage showed greatly increased transport through polarized
      Madin-Darby canine kidney cells transfected with human pIgR. This transport was
      not affected by pIgA nor did it inhibit pIgR-mediated pIgA transcytosis. A free
      peptide of identical amino acid sequence as that displayed by the C9A phage
      inhibited phage interaction with SC. This implied that the C9A peptide sequence
      may be exploited for pIgR-mediated epithelial transport without interfering with
      secretory immunity.

PMID- 16423832
TI  - Smoothened regulates activator and repressor functions of Hedgehog signaling via
      two distinct mechanisms.
AB  - The secreted protein Hedgehog (Hh) plays an important role in metazoan
      development and as a survival factor for many human tumors. In both cases, Hh
      signaling proceeds through the activation of the seven-transmembrane protein
      Smoothened (Smo), which is thought to convert the Gli family of transcription
      factors from transcriptional repressors to transcriptional activators. Here, we
      provide evidence that Smo signals to the Hh signaling complex, which consists of
      the kinesin-related protein Costal2 (Cos2), the protein kinase Fused (Fu), and
      the Drosophila Gli homolog cubitus interruptus (Ci), in two distinct manners. We
      show that many of the commonly observed molecular events following Hh signaling
      are not transmitted in a linear fashion but instead are activated through two
      signals that bifurcate at Smo to independently affect activator and repressor
      pools of Ci.

PMID- 16423834
TI  - Tissue kallikrein mK13 is a candidate processing enzyme for the precursor of
      interleukin-1beta in the submandibular gland of mice.
AB  - By using Western blot analysis, high levels of 17.5- and 20-kDa interleukin-1beta
      (IL-1beta) proteins were detected in the submandibular gland (SMG) of mice.
      Despite this fact, the amount of pro-IL-1beta protein, a precursor of IL-1beta,
      with a molecular size of 35 kDa in this tissue was below the detectable level,
      although strong expression of pro-IL-1beta mRNA was observed. A large amount of
      17.5-kDa IL-1beta also appeared in the saliva of mice injected with
      lipopolysaccharide, suggesting that this IL-1beta is a secretory form produced by
      the SMG. The protein for IL-1beta-converting enzyme, a processing enzyme for pro
      IL-1beta, was expressed only at a low level in the SMG as compared with its level
      in various epithelial tissues or lipopolysaccharide-stimulated macrophages. On
      the other hand, mK1, mK9, mK13, and mK22, members of the kallikrein family, were
      detected strongly in the SMG but not in other tissues. By incubation with mK13,
      but not with mK1, mK9, or mK22, the 35-kDa pro-IL-1beta was cleaved into two
      major products with molecular masses of 17.5 and 22 kDa, and production was
      inhibited by phenylmethylsulfonyl fluoride, a serine protease inhibitor, but not
      by IL-1beta-converting enzyme inhibitors. A peptide segment corresponding to
      amino acid residues 107-121 of mouse pro-IL-1beta (107WDDDDNLLVCDVPIR) was
      cleaved by incubation with mK13, generating two peptides, 107WDDDDNL and
      114LVCDVPIR. Therefore, kallikrein mK13 would appear to hydrolyze pro-IL-1beta
      between its Leu113 and Leu114 residues. The results of immunohistochemistry and
      an autonomic therapy experiment showed that IL-1beta and kallikrein mK13 were co
      localized in the secretory granules of granular convoluted tubular cells. Our
      present results thus suggest kallikrein mK13 is a plausible candidate for the
      processing enzyme for pro-IL-1beta in the SMG of mice.

PMID- 16423835
TI  - Limitations of a case-control study on bisphenol A (BPA) serum levels and
      recurrent miscarriage.

PMID- 16423836
TI  - Total and active ghrelin levels in women with polycystic ovary syndrome.

PMID- 16423837
TI  - Use of washed sperm for assisted reproduction in HIV-positive males without
      checking viral absence. A risky business?

PMID- 16423838
TI  - Comment on 'Season of birth influences the timing of menopause'.

PMID- 16423839
TI  - Is 250 microg rHCG always better and safer than 500 microg rHCG?

PMID- 16423840
TI  - Alemtuzumab, fludarabine and melphalan as a conditioning therapy in severe
      aplastic anemia and hypoplastic myelodysplastic syndrome--single center
      experience.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation is the treatment
      of choice in young patients with severe aplastic anemia. The main causes of
      failure after this procedure are graft versus host disease, infections and graft
      failure, often exacerbated by large numbers of transfusions and prolonged disease
      duration before transplant. METHODS: We report the results of allografting
      following conditioning with fludarabine, alemtuzumab and melphalan in: five
      patients with severe aplastic anemia and one with hypoplastic myelodysplastic
      syndrome. All patients had matched sibling donors. Source of hematopoietic stem
      cell was: bone marrow-2, blood-3, bone marrow and blood-1. The age of recipients
      was 18-26 years. Four patients received their graft as the first line therapy and
      two after failure of cyclosporine and antithymocyte globulin treatment. Number of
      transfused units including red blood cells and platelets before transplantation
      was 8-100 (median: 22) and 10-32 (median: 11), respectively. All donors and
      recipients were CMV-seropositive. Conditioning consisted of: alemtuzumab 30 mg/d
      (day -7 to -5), fludarabine 30 mg/m(2) (days -7 to -3) and melphalan 140 mg/m(2)
      at the day -2. RESULTS: The time to granulocytes and platelets recovery was 15
      and 25 days, respectively. All patients achieved full donor chimerism on day +60.
      Only two patients needed ganciclovir as preemptive therapy. Recurrent parvovirus
      B19 infection with pure red cell aplasia and acute viral B hepatitis was observed
      in one case. Pure red cell aplasia was successfully treated with immunoglobulins
      and cyclosporine discontinuation. With a follow-up of 16-39 (median: 29) months
      all patients are alive, and neither graft failure nor graft versus host disease,
      or any no other severe complications, was observed. CONCLUSIONS: Our study
      suggests that transplantation of hematopoietic stem cell using alemtuzumab,
      fludarabine and melphalan as a conditioning therapy is safe, inexpensive and
      effective treatment for patients with severe aplastic anemia, including multi
      transfused adults having their disease for a long time.

PMID- 16423841
TI  - Tobacco smoking and colorectal cancer risk: an evaluation based on a systematic
      review of epidemiologic evidence among the Japanese population.
AB  - BACKGROUND: It is unclear whether tobacco smoking is related to colorectal cancer
      risk in Japan. We evaluated the association among the Japanese population based
      on a systematic review of epidemiologic evidence. METHODS: Original data were
      obtained from searches of MEDLINE using PubMed, complemented with manual
      searches. The evaluation of associations was based on the strength of evidence
      and the magnitude of association, together with biological plausibility as
      previously evaluated by the International Agency for Research on Cancer. RESULTS:
      A total of six cohort studies and 15 case-control studies were thus identified. A
      substantial degree of heterogeneity was observed in the association between
      smoking and colon cancer; most case-control studies published before 1994
      reported an inverse association, whereas studies conducted over the last decade
      did not find any significant association. Recent cohort studies have shown a non
      significant 20-40% increase in colon cancer risk associated with current smoking.
      Several recent case-control studies and some cohort studies have identified a
      weak to strong positive association between smoking and rectal cancer.
      CONCLUSION: We conclude that tobacco smoking possibly increases the risk of
      colorectal cancer among the Japanese population. More specifically, tobacco
      smoking may possibly increase the risk of rectal cancer; however, epidemiologic
      evidence is still insufficient to demonstrate any clear association with colon
      cancer.

PMID- 16423842
TI  - Effect of the Integrated Management of Childhood Illness strategy on health care
      quality in Morocco.
AB  - OBJECTIVE: To evaluate an intervention to promote health workers' use of the
      World Health Organization's Integrated Management of Childhood Illness clinical
      guidelines and to identify other factors influencing quality of care received by
      Moroccan children. SETTING: Public outpatient health facilities. DESIGN: Cross
      sectional survey of consultations with sick children under 5 years old at
      facilities in two intervention and two comparison provinces in April 2000 (6-12
      months after intervention). Consultations were observed, children's caretakers
      and health workers were interviewed, and children were re-examined by a 'gold
      standard' study clinician. STUDY PARTICIPANTS: Probability sample of 467
      consultations (97.9% participation) performed by 101 health workers in 62
      facilities. INTERVENTION: Health workers received in-service training with job
      aids and a follow-up visit with feedback 4-6 weeks after training. MAIN OUTCOME
      MEASURES: Index of overall guideline adherence (mean percentage of recommended
      tasks that were done per child) and the percentage of children requiring
      antibiotics correctly prescribed antibiotics. RESULTS: Quality of care was better
      in intervention provinces, according to the adherence index (79.7 versus 19.5%, P
      < 0.0001), correct prescription of antibiotics (60.8 versus 31.3%, P = 0.0013),
      and other indicators. Multivariate modeling revealed a variety of factors
      significantly associated with quality, including health worker attributes (pre
      service training, residence in government-subsidized housing, sex, and opinions)
      and child/consultation attributes (child's age and temperature, number of chief
      complaints, and caretaker type). CONCLUSIONS: Exposure to the intervention was
      strongly associated with adherence to the guidelines and correct prescribing of
      antibiotics 6-12 months after exposure. Many other factors may influence health
      worker performance.

PMID- 16423843
TI  - Directed evolution of RuBisCO hypermorphs through genetic selection in engineered
      E.coli.
AB  - The Calvin Cycle is the primary conduit for the fixation of carbon dioxide into
      the biosphere; ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO)
      catalyzes the rate-limiting fixation step. Our goal is to direct the evolution of
      RuBisCO variants with improved kinetic and biophysical properties. The Calvin
      Cycle was partially reconstructed in Escherichia coli; the engineered strain
      requires the Synechococcus PCC6301 RuBisCO for growth in minimal media
      supplemented with a pentose. We randomly mutated the gene encoding the large
      subunit of RuBisCO (rbcL), co-expressed the resulting library with the small
      subunit (rbcS) and the Synechococcus PCC7492 phosphoribulokinase (prkA), and
      selected hypermorphic variants. The RuBisCO variants that evolved during three
      rounds of random mutagenesis and selection were over-expressed, and exhibited 5
      fold improvement in specific activity relative to the wild-type enzyme. These
      results demonstrate a new strategy for the artificial selection of RuBisCO and
      other non-native metabolic enzymes.

PMID- 16423844
TI  - Characterization of an FcgammaRI-binding peptide selected by phage display.
AB  - The high-affinity IgG receptor, Fcgamma receptor I (FcgammaRI), is expressed
      exclusively on myeloid cells, and there is a great interest in the targeting of
      vaccine antigens to FcgammaRI using anti-human FcgammaRI antibodies or fragments
      derived from such molecules. In order to reduce the size and complexity of the
      targeting reagent, we have searched for FcgammaRI binding peptides in peptide
      libraries displayed on phage. The human monocytic cell line U937 was used as
      target. Phages that displayed the consensus peptide CLRSGXGC were selected and
      revealed increased binding to IFN-gamma stimulated versus non-stimulated U937
      cells as well as to FcgammaRI transfected versus non-transfected IIA1.6 cells.
      Furthermore, they bound the extracellular domains of soluble FcgammaRI, but
      neither FcgammaRIIA, FcgammaRIIB nor FcgammaRIIIB. Binding was inhibited by a
      synthetic version of the peptide, whereas neither human IgG nor the FcgammaRI
      specific monoclonal antibodies (mAb) mAb22 and 32.2 interfered. Flow-cytometry
      analysis and internalization studies showed that a synthetic biotin-conjugated
      peptide ADGACLRSGRGCGAAK-bio was able to target U937 cells and FcgammaRI
      transfected IIA1.6 cells, and further to promote internalization and vesicular
      degradation of streptavidin coupled to 1 microm magnetic beads. These peptides
      may have potential as FcgammaRI targeting reagents.

PMID- 16423845
TI  - Functional analysis of organophosphorus hydrolase variants with high degradation
      activity towards organophosphate pesticides.
AB  - Organophosphorus hydrolase (OPH, also known as phosphotriesterase) is a bacterial
      enzyme that is capable of degrading a wide range of neurotoxic organophosphate
      nerve agents. Directed evolution has been used to generate one variant (22A11)
      with up to 25-fold improved hydrolysis of methyl parathion. Surprisingly, this
      variant also degraded all other substrates (paraoxon, parathion and coumaphos)
      tested 2- to 10-fold faster. Since only one mutation (H257Y) is directly located
      in the active site, site-directed mutagenesis and saturation mutagenesis were
      used to identify the role of the other distal substitutions (A14T, A80V, K185R,
      H257Y, I274N) on substrate specificity and activity. Sequential site-directed
      mutagenesis indicated that K185R and I274N are the most important substitutions,
      leading to an improvement not only in the hydrolysis of methyl parathion but also
      the overall hydrolysis rate of all other substrates tested. Using structural
      modeling, these two mutations were shown to favor the formation of hydrogen bonds
      with nearby residues, resulting in structural changes that could alter the
      overall substrate hydrolysis.

PMID- 16423846
TI  - Variable gap penalty for protein sequence-structure alignment.
AB  - The penalty for inserting gaps into an alignment between two protein sequences is
      a major determinant of the alignment accuracy. Here, we present an algorithm for
      finding a globally optimal alignment by dynamic programming that can use a
      variable gap penalty (VGP) function of any form. We also describe a specific
      function that depends on the structural context of an insertion or deletion. It
      penalizes gaps that are introduced within regions of regular secondary structure,
      buried regions, straight segments and also between two spatially distant
      residues. The parameters of the penalty function were optimized on a set of 240
      sequence pairs of known structure, spanning the sequence identity range of 20
      40%. We then tested the algorithm on another set of 238 sequence pairs of known
      structures. The use of the VGP function increases the number of correctly aligned
      residues from 81.0 to 84.5% in comparison with the optimized affine gap penalty
      function; this difference is statistically significant according to Student's t
      test. We estimate that the new algorithm allows us to produce comparative models
      with an additional approximately 7 million accurately modeled residues in the
      approximately 1.1 million proteins that are detectably related to a known
      structure.

PMID- 16423847
TI  - Multicenter randomized phase III study of the cardioprotective effect of
      dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated
      with anthracycline-based chemotherapy.
AB  - BACKGROUND: Anthracycline-induced cardiotoxicity has led to the adoption of
      empirical dose limits that may restrict continued use of anthracyclines among
      patients who might benefit. Dexrazoxane, a cardioprotective agent, has been shown
      to reduce the risk of anthracycline-associated cardiotoxicity when given from
      first dose of anthracycline. This study sought to confirm the benefit of
      dexrazoxane in patients at high risk of cardiotoxicity due to prior anthracycline
      use. PATIENTS AND METHODS: A total of 164 female breast cancer patients,
      previously treated with anthracyclines, received anthracycline-based chemotherapy
      either with (n = 85) or without (n = 79) dexrazoxane for a maximum of six cycles.
      RESULTS: Compared with those receiving anthracycline alone, patients treated with
      dexrazoxane experienced significantly fewer cardiac events (39% versus 13%, P <
      0.001) and a lower and less severe incidence of congestive heart failure (11%
      versus 1%, P < 0.05). Tumor response rate was unaffected by dexrazoxane therapy.
      The frequency of adverse events was similar between groups and there were no
      significant between-group differences in the number of dose
      modifications/interruptions. CONCLUSION: Dexrazoxane significantly reduced the
      occurrence and severity of anthracycline-induced cardiotoxicity in patients at
      increased risk of cardiac dysfunction due to previous anthracycline treatment
      without compromising the antitumor efficacy of the chemotherapeutic regimen.

PMID- 16423848
TI  - A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus
      carboplatin treatment in patients with extended disease small-cell lung cancer.
AB  - BACKGROUND: Superiority of irinotecan/cisplatin over etoposide/cisplatin was
      suggested in small-cell lung cancer (SCLC). This trial investigated
      irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP). PATIENTS AND
      METHODS: The interim analysis at the phase II/phase III transition point of the
      multicenter trial is reported. Extensive disease SCLC patients were randomized to
      receive carboplatin AUC 5 mg x min/ml either in combination with 50 mg/m2 of
      irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m2 days 1-3 (EP).
      The primary end point was response rate and the secondary end points were
      toxicity and progression-free survival. RESULTS: Seventy patients were
      randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus
      48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P < 0.01) were found.
      Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P =
      0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm,
      respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1
      10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03).
      CONCLUSIONS: IP is active, less toxic and appears to improve PFS. Based on the
      phase II results the trial has been extended to phase III to assess the impact on
      overall survival.

PMID- 16423850
TI  - Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons
      both in vitro and in vivo.
AB  - Cyclothiazide (CTZ) is a potent blocker of AMPA receptor desensitization. We have
      recently demonstrated that CTZ also inhibits GABA(A) receptors. Here we report
      that CTZ induces robust epileptiform activity in hippocampal neurons both in
      vitro and in vivo. We first found that chronic treatment of hippocampal cultures
      with CTZ (5 microM, 48 h) results in epileptiform activity in the majority of
      neurons (80%). The epileptiform activity lasts more than 48 h after washing off
      CTZ, suggesting a permanent change of the neural network properties after CTZ
      treatment. We then demonstrated in in vivo recordings that injection of CTZ (5
      micromol in 5 microl) into the lateral ventricles of anaesthetized rats also
      induces spontaneous epileptiform activity in the hippocampal CA1 region. The
      epileptogenic effect of CTZ is probably due to its enhancing glutamatergic
      neurotransmission as shown by increasing the frequency and decay time of mEPSCs,
      and simultaneously inhibiting GABAergic neurotransmission by reducing the
      frequency of mIPSCs. Comparing to a well-known epileptogenic agent kainic acid
      (KA), CTZ affects neuronal activity mainly through modulating synaptic
      transmission without significant change of the intrinsic membrane excitability.
      Unlike KA, which induces significant cell death in hippocampal cultures, CTZ
      treatment does not result in any apparent neuronal death. Therefore, the CTZ
      induced epilepsy model may provide a novel research tool to elucidate the
      molecular and cellular mechanisms of epileptogenesis without any complication
      from drug-induced cell death. The long-lasting epileptiform activity after CTZ
      washout may also make it a very useful model in screening antiepileptic drugs.

PMID- 16423849
TI  - A possible role of the junctional face protein JP-45 in modulating Ca2+ release
      in skeletal muscle.
AB  - We investigated the functional role of JP-45, a recently discovered protein of
      the junctional face membrane (JFM) of skeletal muscle. For this purpose, we
      expressed JP-45 C-terminally tagged with the fluorescent protein DsRed2 by
      nuclear microinjection in myotubes derived from the C2C12 skeletal muscle cell
      line and performed whole-cell voltage-clamp experiments. We recorded in parallel
      cell membrane currents and Ca(2+) signals using fura-2 during step
      depolarization. It was found that properties of the voltage-activated Ca(2+)
      current were not significantly changed in JP-45-DsRed2-expressing C2C12 myotubes
      whereas the amplitude of depolarization-induced Ca(2+) transient was decreased
      compared to control myotubes expressing only DsRed2. Converting Ca(2+) transients
      to Ca(2+) input flux using a model fit approach to quantify Ca(2+) removal, the
      change could be attributed to an alteration in voltage-activated Ca(2+)
      permeability rather than to altered removal properties or a lower Ca(2+) content
      of the sarcoplasmic reticulum (SR). Determining non-linear capacitive currents
      revealed a reduction of Ca(2+) permeability per voltage-sensor charge. The
      results may be explained by a modulatory effect of JP-45 related to its reported
      in vitro interaction with the dihydropyridine receptor and the SR Ca(2+) binding
      protein calsequestrin (CSQ).

PMID- 16423851
TI  - T-type Ca2+ channels encode prior neuronal activity as modulated recovery rates.
AB  - T-type Ca2+ channels give rise to low-threshold inward currents that are central
      determinants of neuronal excitability. The availability of T-type Ca2+ channels
      is strongly influenced by voltage-dependent inactivation and recovery from
      inactivation. Here, we show that native and cloned T-type Ca2+ channel subunits
      selectively encode specific aspects of prior membrane potential changes via a
      powerful modulation of the rates with which these channels recover from
      inactivation. Increasing the duration of subthreshold (-70 to -55 mV)
      conditioning depolarizations caused a pronounced slowing of subsequent recovery
      from inactivation of both cloned (Ca(v)3.1-3.3) and native T-type channels
      (thalamic neurones). The scaling of recovery rates with increasing duration of
      conditioning depolarizations could be well described by a power law function.
      Different T-type channel isoforms exhibited overlapping but complementary ranges
      of recovery rates. Intriguingly, scaling of recovery rates was dramatically
      reduced in Ca(v)3.2 and Ca(v)3.3, but not Ca(v)3.1 subunits, when mock action
      potentials were superimposed on conditioning depolarizations. Our results suggest
      that different T-type channel subunits exhibit dramatic differences in scaling
      relationships, in addition to well-described differences in other biophysical
      properties. Furthermore, the availability of T-type channels is powerfully
      modulated over time, depending on the patterns of prior activity that these
      channels have encountered. These data provide a novel mechanism for cellular
      short-term plasticity on the millisecond to second time scale that relies on
      biophysical properties of specific T-type Ca2+ channel subunits.

PMID- 16423852
TI  - Pore properties and pharmacological features of the P2X receptor channel in
      airway ciliated cells.
AB  - Airway ciliated cells express an ATP-gated P2X receptor channel of unknown
      subunit composition (P2X(cilia)) which is modulated by Na+ and by long exposures
      to ATP. P2X(cilia) was investigated by recording currents from freshly
      dissociated rabbit airway ciliated cells with the patch-clamp technique in the
      whole-cell configuration. During the initial continuous exposure to extracellular
      ATP, P2X(cilia) currents gradually increase in magnitude (priming), yet the
      permeability to N-methyl-D-glucamine (NMDG) does not change, indicating that
      priming does not arise from a progressive change in pore diameter. Na+, which
      readily permeates P2X(cilia) receptor channels, was found to inhibit the channel
      extracellular to the electric field. The rank order of permeability to various
      monovalent cations is: Li+, Na+, K+, Rb+, Cs+, NMDG+ and TEA+, with a relative
      permeability of 1.35, 1.0, 0.99, 0.91, 0.79, 0.19 and 0.10, respectively. The
      rank order for the alkali cations follows an Eisenman series XI for a high
      strength field site. Ca2+ has been estimated to be 7-fold more permeant than Na+.
      The rise in [Ca2+]i in ciliated cells, induced by the activation of P2X(cilia),
      is largely inhibited by either Brilliant Blue G or KN-62, indicating that P2X7
      may be a part of P2X(cilia). P2X(cilia) is augmented by Zn2+ and by ivermectin,
      and P2X4 receptor protein is detected by immunolabelling at the basal half of the
      cilia, strongly suggesting that P2X4 is a component of P2X(cilia) receptor
      channels. Taken together, these results suggest that P2X(cilia) is either
      assembled from P2X4 and P2X7 subunits, or formed from modified P2X4 subunits.

PMID- 16423853
TI  - The anti-angiogenic VEGF isoform VEGF165b transiently increases hydraulic
      conductivity, probably through VEGF receptor 1 in vivo.
AB  - Vascular endothelial growth factor (VEGF) is the principal agent that increases
      microvascular permeability during physiological and pathological angiogenesis.
      VEGF is differentially spliced to form two families of isoforms: VEGF(xxx), and
      VEGF(xxx)b. Whereas VEGF(165) stimulates angiogenesis, VEGF(165)b is anti
      angiogenic. To determine the effect of VEGF(165)b on permeability, hydraulic
      conductivity (L(p)) was measured in individually perfused microvessels in the
      mesentery of frogs and rats. As with VEGF(165), VEGF(165)b increased L(p) in
      amphibian (2.4 +/- 0.3-fold) and mammalian (1.9 +/- 0.2-fold) mesenteric
      microvessels. A dose-response relationship showed that VEGF(165)b (EC(50), 0.65
      pm) was approximately 25 times more potent than VEGF(165) (EC(50), 16 pm) in
      amphibian microvessels. VEGF(165) has been shown to increase permeability through
      VEGF receptor 2 (VEGF-R2) signalling. However, VEGF(165)b increased L(p) of frog
      vessels to the same extent in the presence of the VEGF-R2 inhibitor ZM323881,
      indicating that it does not increase permeability via VEGF-R2 signalling, and was
      inhibited by the VEGF receptor inhibitor SU5416 at doses that are specific for
      VEGF receptor 1 (VEGF-R1). VEGF(165)b, in contrast to VEGF(165), did not result
      in a sustained chronic increase in L(p). These results show that although
      VEGF(165)b is anti-angiogenic in the mesentery, it does signal in endothelial
      cells in vivo resulting in a transient, but not sustained, increase in
      microvascular L(p), probably through VEGF-R1.

PMID- 16423854
TI  - Neonatal programming of the rat neuroimmune response: stimulus specific changes
      elicited by bacterial and viral mimetics.
AB  - Recently, it has been shown that the neonatal immune environment can have
      significant programming effects on the adult neuroimmune response. A single
      neonatal immune challenge with the bacterial mimetic lipopolysaccharide (LPS) can
      alter the neuroendocrine, neurochemical and febrile responses to a subsequent,
      homotypic (LPS) immune challenge as adults. As the programming effects of viral
      stimuli during this neonatal period are unknown, we tested whether the viral
      mimetic polyinosinic-polycytidylic acid (PolyIC), administered on postnatal day
      14 (P14) would alter the adult neuroimmune responses to a subsequent PolyIC
      challenge. Our results show that animals treated neonatally with PolyIC had
      significantly attenuated febrile responses to an adult PolyIC challenge, which
      coincided with a heightened corticosteroid response. When the corticosteroid
      receptor blocker RU486 was administered prior to the adult PolyIC challenge,
      animals treated neonatally with PolyIC no longer displayed attenuated febrile
      responses. Similar responses to an adult LPS challenge have been seen in animals
      that were exposed neonatally to LPS, indicating that both neonatal immune stimuli
      elicit highly similar programming effects on the adult neuroimmune responses.
      However, we find that neither neonatal PolyIC nor neonatal LPS challenges led to
      an alteration in the adult febrile or corticosteroid responses to a heterotypic
      adult immune challenge, indicating that the programming effects of the neonatal
      immune environment are stimulus specific, and do not alter the adult responses to
      other immune stimuli.

PMID- 16423855
TI  - Differential effects of prenatal exposure to dexamethasone or cortisol on
      circulatory control mechanisms mediated by angiotensin II in the central nervous
      system of adult sheep.
AB  - Prenatal exposure to elevated maternal glucocorticoids (dexamethasone (DEX) or
      cortisol (CORT)) for 2 days early in pregnancy can 'programme' alterations in
      adult offspring of sheep, including elevated arterial pressure. DEX treatment
      also results in greater angiotensin II type 1 (AT1) receptor expression in the
      medulla oblongata in late gestation fetuses than in saline (SAL)- or CORT-exposed
      animals. We hypothesized that this would result in functional changes in
      brainstem angiotensinergic control of cardiovascular function in DEX- but not
      CORT-exposed animals. To test this hypothesis, cardiovascular responses to
      intracerebroventricular (I.C.V.) angiotensin II were examined in adult male
      offspring exposed to DEX (0.48 mg h(-1); n = 7), CORT (5 mg h(-1), n = 6) or SAL
      (n = 9) from 26 to 28 days of gestation. Increases in mean arterial pressure
      during i.c.v. infusion of angiotensin II (1 or 10 microg h(-1)) were
      significantly greater in the DEX group (10 +/- 1 mmHg at 1 microg h(-1)) compared
      with SAL (6 +/- 1 mmHg) or CORT (6 +/- 1 mmHg) animals (P < 0.05). I.C.V.
      infusion of the AT1 antagonist losartan significantly decreased cardiac output
      and heart rate in DEX animals, but not in SAL or CORT animals. Thus, increased
      expression of brainstem AT1 receptor mRNA after prenatal DEX is associated with
      increased responsiveness of cardiovascular control to activation of brain AT
      receptors by exogenous and endogenous angiotensin II. The altered role of the
      brain RAS in sheep exposed prenatally to DEX was not observed in sheep exposed
      prenatally to cortisol, suggesting these two glucocorticoids have distinct
      programming actions.

PMID- 16423856
TI  - Mechanisms underlying variations in excitation-contraction coupling across the
      mouse left ventricular free wall.
AB  - Ca(2+) release during excitation-contraction (EC) coupling varies across the left
      ventricular free wall. Here, we investigated the mechanisms underlying EC
      coupling differences between mouse left ventricular epicardial (Epi) and
      endocardial (Endo) myocytes. We found that diastolic and systolic [Ca(2+)](i) was
      higher in paced Endo than in Epi myocytes. Our data indicated that differences in
      action potential (AP) waveform between Epi and Endo cells only partially
      accounted for differences in [Ca(2+)](i). Rather, we found that the amplitude of
      the [Ca(2+)](i) transient, but not its trigger - the Ca(2+) current - was larger
      in Endo than in Epi cells. We also found that spontaneous Ca(2+) spark activity
      was about 2.8-fold higher in Endo than in Epi cells. Interestingly, ryanodine
      receptor type 2 (RyR2) protein expression was nearly 2-fold higher in Endo than
      in Epi myocytes. Finally, we observed less Na(+)-Ca(2+) exchanger function in
      Endo than in Epi cells, which was associated with decreased Ca(2+) efflux during
      the AP; this contributed to higher diastolic [Ca(2+)](i) and SR Ca(2+) in Endo
      than in Epi cells during pacing. We propose that transmural differences in AP
      waveform, SR Ca(2+) release, and Na(+)-Ca(2+) exchanger function underlie
      differences in [Ca(2+)](i) and EC coupling across the left ventricular free wall.

PMID- 16423857
TI  - Cycling efficiency in humans is related to low UCP3 content and to type I fibres
      but not to mitochondrial efficiency.
AB  - The purpose of this study was to investigate the hypothesis that cycling
      efficiency in vivo is related to mitochondrial efficiency measured in vitro and
      to investigate the effect of training status on these parameters. Nine endurance
      trained and nine untrained male subjects (V(O2peak) = 60.4 +/- 1.4 and 37.0 +/-
      2.0 ml kg(-1) min(-1), respectively) completed an incremental submaximal
      efficiency test for determination of cycling efficiency (gross efficiency, work
      efficiency (WE) and delta efficiency). Muscle biopsies were taken from m. vastus
      lateralis and analysed for mitochondrial respiration, mitochondrial efficiency
      (MEff; i.e. P/O ratio), UCP3 protein content and fibre type composition (% MHC
      I). MEff was determined in isolated mitochondria during maximal (state 3) and
      submaximal (constant rate of ADP infusion) rates of respiration with pyruvate.
      The rates of mitochondrial respiration and oxidative phosphorylation per muscle
      mass were about 40% higher in trained subjects but were not different when
      expressed per unit citrate synthase (CS) activity (a marker of mitochondrial
      density). Training status had no influence on WE (trained 28.0 +/- 0.5, untrained
      27.7 +/- 0.8%, N.S.). Muscle UCP3 was 52% higher in untrained subjects, when
      expressed per muscle mass (P < 0.05 versus trained). WE was inversely correlated
      to UCP3 (r = -0.57, P < 0.05) and positively correlated to percentage MHC I (r =
      0.58, P < 0.05). MEff was lower (P < 0.05) at submaximal respiration rates (2.39
      +/- 0.01 at 50% V(O2max)) than at state 3 (2.48 +/- 0.01) but was neither
      influenced by training status nor correlated to cycling efficiency. In conclusion
      cycling efficiency was not influenced by training status and not correlated to
      MEff, but was related to type I fibres and inversely related to UCP3. The inverse
      correlation between WE and UCP3 indicates that extrinsic factors may influence
      UCP3 activity and thus MEff in vivo.

PMID- 16423858
TI  - Static and dynamic gamma-motor output to ankle flexor muscles during locomotion
      in the decerebrate cat.
AB  - In locomotion, the flexor muscles of the leg are mainly concerned with the
      relatively constant task of raising the foot, whereas the extensors have the more
      variable task of support and propulsion at different speeds. This suggests that
      the way in which the fusimotor system works may differ between the two muscle
      groups. Observations previously made of the static and dynamic gamma-motor firing
      patterns in the ankle extensor medial gastrocnemius (MG) have therefore been
      repeated in the flexor tibialis anterior (TA). One or more single gamma-motor
      axons, dissected from a small filament of TA nerve, were recorded simultaneously
      with a number of single spindle afferents in dorsal rootlets. Cats were
      decerebrated and locomoted spontaneously on a treadmill. Identification of each
      gamma-motor axon depended on relating the changes in firing caused by midbrain
      stimulation to the changes in static and dynamic behaviour of the spindle
      afferents in response to repetitive ramp and hold stretches. Static gamma axons
      all showed a smooth modulation in frequency, increasing in phase with muscle
      shortening, superimposed on a minimum frequency of about 20-30 impulses s(-1).
      Dynamic gamma axons showed interrupted firing with the frequency rising abruptly
      from zero at the onset of shortening, and falling again to zero shortly after the
      onset of lengthening. The frequency during the active periods was relatively
      constant, even when movement amplitudes varied. The basic similarity in the
      static and dynamic gamma discharge patterns for the two muscles suggests that the
      strategy of gamma-motor control is common to both flexors and extensors. The
      static gamma pattern is thought to be a 'temporal template' of the expected
      movement, effectively expanding the dynamic response range of the spindles in
      active movements. The dynamic gamma pattern sensitizes the primary afferents to
      detect the onset of muscle lengthening and to detect departures from the intended
      movement trajectory.

PMID- 16423859
TI  - Fundamental importance of Na+-Ca2+ exchange for the pacemaking mechanism in
      guinea-pig sino-atrial node.
AB  - Na+-Ca2+ exchange (NCX) current has been suggested to play a role in cardiac
      pacemaking, particularly in association with Ca2+ release from the sarcoplasmic
      reticulum (SR) that occurs just before the action potential upstroke. The present
      experiments explore in more detail the contribution of NCX to pacemaking. Na+
      Ca2+ exchange current was inhibited by rapid switch to low-Na+ solution (with Li+
      replacing Na+) within the time course of a single cardiac cycle to avoid slow
      secondary effects. Rapid switch to low-Na+ solution caused immediate cessation of
      spontaneous action potentials. ZD7288 (3 microM), to block I(f) (funny current)
      channels, slowed but did not stop the spontaneous activity, and tetrodotoxin (10
      microM), to block Na+ channels, had little effect, but in the presence of either
      of these agents, rapid switch to low-Na+ solution again caused immediate
      cessation of spontaneous action potentials. Spontaneous electrical activity was
      also stopped following loading of the cells with the Ca2+ chelators BAPTA and
      EGTA, and by exposure to the NCX inhibitor KB-R7943 (5 microM). When rapid switch
      to low-Na+ solution caused cessation of spontaneous activity, this was found
      (using confocal microscopy, with fluo-4 as the Ca2+ probe) to be accompanied by
      an initial fall in cytosolic [Ca2+], with subsequent appearance of Ca2+ waves.
      Inhibition of SR Ca2+ uptake with cyclopiazonic acid (CPA, 30 microM) slowed but
      did not stop spontaneous activity. Rapid switch to low-Na+ solution in the
      presence of CPA caused abolition of spontaneous Ca2+ transients and a progressive
      rise in cytosolic [Ca2+]. With ratiometric fluorescence methods (indo-5F as the
      Ca2+ probe), the minimum level of [Ca2+] between beats was found to be
      approximately 225 nM, and abolition of beating with nifedipine, acetylcholine or
      adenosine caused a fall in cytosolic [Ca2+] below this level. These observations
      support the hypothesis that NCX current is essential for normal pacemaker
      activity under the conditions of our experiments. A continuous depolarizing
      influence of current through the NCX protein might result from maintained
      electrogenic NCX (with 3:1 stoichiometry, supported by a cytosolic [Ca2+] that
      normally does not fall below 225 nM between beats) and/or from a novel, recently
      suggested role of the NCX protein to allow a Na+ leak pathway.

PMID- 16423861
TI  - Purkinje cells in the lateral cerebellum of the cat encode visual events and
      target motion during visually guided reaching.
AB  - In this study the receipt of visual information by the lateral cerebellum and its
      contribution to a motor output was studied using single unit recording of
      cerebellar cortical neurones in cats trained to perform visually guided reaching.
      The activity of Purkinje cells and other cortical neurones in the lateral
      cerebellum was investigated in relation to various aspects of the task, such as
      visual events, parameters of target movement, and limb and eye movements. Two
      thirds (66%) of Purkinje cells tested could signal simple visual events, such as
      a flash of light. Neurones were also capable of detecting other less potent, but
      behaviourally important visual events, such as a 'GO' signal (LED brightening).
      Half of the cells tested were responsive to the on-going motion of the visual
      target, displaying tonically altered discharge rates for as long as it was
      moving, and a 'preferred' target velocity. A small proportion of cells showed
      short latency visual modulation that persisted during the forelimb reach.
      Anatomical tracing studies confirmed that the recordings were obtained from the
      D1 zone of crus I. In summary, cells in this region of lateral cerebellar cortex
      perform simple visual functions, such as event detection, but also more complex
      visual functions, such as encoding parameters of target motion, and their visual
      responsiveness is appropriate for a role in accurate visually guided reaching to
      a moving target.

PMID- 16423860
TI  - Evaluation of plateau-potential-mediated 'warm up' in human motor units.
AB  - Spinal motor neurones can exhibit sustained depolarization in the absence of
      maintained synaptic or injected current. This phenomenon, referred to as a
      plateau potential, is due to the activation of monoamine-dependent persistent
      inward currents. Accordingly, activation of a plateau potential should result in
      a decrease in the excitatory synaptic drive required to activate a motor unit.
      This, in turn, has been suggested to cause a progressive decline in the muscle
      force at which motor units are recruited during repeated voluntary contractions.
      Such a progressive decrease in threshold force associated with preceding
      activation of a plateau potential is referred to as 'warm up'. Furthermore,
      activation of a plateau potential is thought to manifest itself as a decrease in
      the derecruitment force compared to recruitment force. Multiple muscles, however,
      can contribute to the detected force and their relative contributions may vary
      over time, which could confound measures of recruitment and derecruitment force.
      Therefore, the purpose of this study was to compare the recruitment and
      derecruitment forces of single motor units in the human extensor digitorum and
      tibialis anterior during repetitive triangular-force contractions in which the
      contributions of other muscles had been minimized. In both muscles, we found that
      the recruitment thresholds of single motor units were unchanged during repeated
      contractions, and that the derecruitment force was consistently greater than the
      recruitment force. These results suggest either that plateau potentials were not
      engaged (or were rapidly extinguished) under these experimental conditions or
      that changes in recruitment and derecruitment force are not suitable criteria for
      detecting them.

PMID- 16423862
TI  - Early growth response factor-1 is critical for cholestatic liver injury.
AB  - Hepatocyte injury during cholestasis depends in part on the release of
      proinflammatory mediators that cause neutrophils to accumulate in the liver and
      become activated to damage hepatocytes. The mechanism by which cholestasis
      stimulates production of proinflammatory mediators in the liver is not completely
      understood. The studies presented here tested the hypothesis that the
      transcription factor early growth response factor-1 (Egr-1) is required for
      inflammation to occur in the liver during cholestasis. The results of these
      studies show that Egr-1 was rapidly upregulated, primarily in hepatocytes, in
      mice subjected to bile duct ligation, an animal model of cholestasis. To
      determine whether Egr-1 was required for inflammation and hepatocyte injury
      during cholestasis, bile duct ligation was performed in wild-type and Egr-1
      knockout mice. Hepatocyte injury, neutrophil accumulation, and upregulation of
      macrophage inflammatory protein-2 (MIP-2) and intercellular adhesion molecule-1
      (ICAM-1) in the liver were significantly reduced in Egr-1 knockouts. By contrast,
      levels of tumor necrosis factor-alpha (TNF-alpha) and collagen (i.e., a biomarker
      of liver fibrosis) were not different between wild-types and Egr-1 knockouts
      subjected to bile duct ligation. Because hepatocytes are exposed to elevated
      concentrations of bile acids during cholestasis, it was determined that bile
      acids upregulate Egr-1 in primary mouse hepatocytes. Deoxycholic acid dose
      dependently increased Egr-1 protein in hepatocytes. Results from these studies
      suggest a scenario in which elevated concentrations of bile acids during
      cholestasis increase expression of Egr-1 in hepatocytes. Egr-1 then upregulates
      proinflammatory mediators that cause neutrophils to accumulate in the liver and
      become activated to damage hepatocytes.

PMID- 16423864
TI  - Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Control
      of the false discovery rate applied to the detection of positively selected amino
      acid sites.
AB  - In this article, we consider the probabilistic identification of amino acid
      positions that evolve under positive selection as a multiple hypothesis testing
      problem. The null hypothesis "H0,s: site s evolves under a negative selection or
      under a neutral process of evolution" is tested at each codon site of the
      alignment of homologous coding sequences. Standard hypothesis testing is based on
      the control of the expected proportion of falsely rejected null hypotheses or
      type-I error rate. As the number of tests increases, however, the power of an
      individual test may become unacceptably low. Recent advances in statistics have
      shown that the false discovery rate--in this case, the expected proportion of
      sites that do not evolve under positive selection among those that are estimated
      to evolve under this selection regime--is a quantity that can be controlled.
      Keeping the proportion of false positives low among the significant results
      generally leads to an increase in power. In this article, we show that
      controlling the false detection rate is relevant when searching for positively
      selected sites. We also compare this new approach to traditional methods using
      extensive simulations.

PMID- 16423863
TI  - Diversification and specialization of HIV protease function during in vitro
      evolution.
AB  - Our goal is to understand how enzymes adapt to utilize novel substrates. We and
      others have shown that directed evolution tends to generate enzyme variants with
      broadened substrate specificity. Broad-specificity enzymes are generally
      deleterious to living cells, so this observed trend might be an artifact of the
      most commonly employed high throughput screens. Here, we demonstrate a more
      natural and effective screening strategy for directed evolution. The gene
      encoding model enzyme HIV protease was randomly mutated, and the resulting
      library was expressed in Escherichia coli cells to eliminate cytotoxic broad
      specificity variants. The surviving variants were screened for clones with
      activity against a reporter enzyme. The wild-type human immunodeficiency virus
      type I protease (HIV PR) is cytotoxic and exhibits no detectable activity in
      reactions with beta-galactosidase (BGAL). In contrast, the selected variants were
      nontoxic and exhibited greater activity and specificity against BGAL than did the
      wild-type HIV PR in reactions with any substrate. A single round of whole gene
      random mutagenesis and conventional high-throughput screening does not usually
      effect complete inversions of substrate specificity. This suggests that a
      combination of positive and purifying selection engenders more rapid adaptation
      than positive selection alone.

PMID- 16423865
TI  - Nephrogenic diabetes insipidus, thiazide treatment and renal cell carcinoma.

PMID- 16423866
TI  - Allozyme diversity and morphometrics of Melocactus paucispinus (Cactaceae) and
      evidence for hybridization with M. concinnus in the Chapada Diamantina, North
      eastern Brazil.
AB  - BACKGROUND AND AIMS: Melocacatus paucispinus (Cactaceae) is endemic to the state
      of Bahia, Brazil, and due to its rarity and desirability to collectors it has
      been considered threatened with extinction. This species is usually sympatric and
      inter-fertile with M. concinnus, and morphological evidence for hybridization
      between them is present in some populations. Levels of genetic and morphological
      variation and sub-structuring in populations of these species were assessed and
      an attempt was made to verify the occurrence of natural hybridization between
      them. METHODS: Genetic variability was surveyed using allozymes (12 loci) and
      morphological variability using multivariate morphometric analyses (17 vegetative
      characters) in ten populations of M. paucispinus and three of M. concinnus
      occurring in the Chapada Diamantina, Bahia. KEY RESULTS: Genetic variability was
      low in both species (P = 0.0-33.3, A = 1.0-1.6, H(e) = 0.000-0.123 in M.
      paucispinus; P = 0.0-25.0, A = 1.0-1.4, H(e) = 0.000-0.104 in M. concinnus).
      Deficit of heterozygotes within the populations was detected in both species,
      with high values of F(IS) (0.732 and 0.901 in M. paucispinus and M. concinnus,
      respectively). Evidence of hybridization was detected by the relative allele
      frequency in the two diaphorase loci. High levels of genetic (F(ST) = 0.504 in M.
      paucispinus and 0.349 in M. concinnus) and morphological (A = 0.20 in M.
      paucispinus and 0.17 in M. concinnus) structuring among populations were found.
      CONCLUSIONS: The Melocactus spp. displayed levels of genetic variability lower
      than the values reported for other cactus species. The evidence indicates the
      occurrence of introgression in both species at two sites. The high F(ST) values
      cannot be explained by geographical substructuring, but are consistent with
      hybridization. Conversely, morphological differentiation in M. paucispinus, but
      not in M. concinnus, is probably due to isolation by distance.

PMID- 16423868
TI  - A multistep kinase-based sertoli cell autocrine-amplifying loop regulates
      prostaglandins, their receptors, and cytokines.
AB  - In Sertoli epithelial cells, the IL-1beta induces prostaglandins (PG) PGE(2),
      PGF(2alpha) and PGI(2) (7-, 11-, and 2-fold, respectively), but not PGD(2),
      production. Cyclohexamide pretreatment inhibiting protein synthesis prevents IL
      1beta increases in PG levels, indicating that induction requires de novo protein
      synthesis. IL-1beta-regulated PGE(2) and PGF(2alpha) production and cytokine
      expression require activation of cyclooxygenase-2 (COX-2) and c-Jun NH(2)
      terminal kinase, as shown using specific enzyme inhibition. PGE(2) and
      PGF(2alpha) stimulate expression of IL-1alpha, -1beta, and -6, findings
      consistent with PG involvement in IL signaling within the seminiferous tubule.
      PGE(2) and PGF(2alpha) reverse COX-2-mediated inhibition of IL-1beta induction of
      cytokine expression and PG production. Sertoli PG receptor expression was
      determined; four known E-prostanoid receptor (EP) subtypes (1-4) and the F
      prostanoid and prostacyclin prostanoid receptors were demonstrated using RNA and
      protein analyses. Pharmacological characterization of Sertoli PG receptors
      associated with cytokine regulation was ascertained by quantitative real-time RT
      PCR analyses. IL-1beta regulates both EP(2) mRNA and protein levels, data
      consistent with a regulatory feedback loop. Butaprost (EP(2) agonist) and 11
      deoxy PGE(1) (EP(2) and EP(4) agonist) treatments show that EP(2) receptor
      activation stimulates Sertoli cytokine expression. Consistent with EP(2)-cAMP
      signaling, protein kinase A inhibition blocks both IL-1beta- and PGE(2)-induced
      cytokines. Together, the data indicate an autocrine-amplifying loop involving IL
      1beta-regulated Sertoli function mediated by COX-2-induced PGE(2) and PGF(2alpha)
      production. PGE(2) activates EP(2) and/or EP(4) receptor(s) and the protein
      kinase A-cAMP pathway; PGF(2alpha) activates F-prostanoid receptor-protein kinase
      C signaling. Further identification of the molecular mechanisms subserving these
      mediators may offer new insights into physiological events as well as
      proinflammatory-mediated pathogenesis in the testis.

PMID- 16423867
TI  - Effects of cultivar, fruit number and reflected photosynthetically active
      radiation on Fragaria x ananassa productivity and fruit ellagic acid and ascorbic
      acid concentrations.
AB  - BACKGROUND AND AIMS: A number of strawberry varieties were surveyed for their
      total ellagic acid concentration, and attempts were made to determine if ellagic
      acid and ascorbic acid concentrations of two strawberry cultivars could be
      increased by polythene reflective mulches. METHODS: After adjusting crop yields
      and cultivation using polythene mulches with two different PAR reflective
      capacities, field- and polytunnel-grown strawberries were analysed for ellagic
      acid and ascorbic acid concentrations by HPLC. Comparative measurements of yield
      and fruit quality were determined along with plant developmental changes. KEY
      RESULTS: Ellagic acid concentration varied widely with strawberry cultivar (60
      341 microg g(-1) frozen weight), as did the ratio of conjugated ellagic acid :
      free ellagic acid. Also, there was significant year-to-year variation in total
      ellagic acid concentration with some cultivars. Mulches with different reflective
      capacities impacted on strawberry production; highly reflective mulches
      significantly increased growth and yield, the latter due to increases in fruit
      size and number. CONCLUSIONS: Highly reflective mulches significantly increased
      total concentrations of ellagic acid and ascorbic acid relative to control in
      fruit of different cultivars. The potential of agronomic practices to enhance the
      concentration and amounts of these important dietary bioactive compounds is
      discussed.

PMID- 16423869
TI  - A dominant-negative human growth hormone-releasing hormone (GHRH) receptor splice
      variant inhibits GHRH binding.
AB  - GHRH is a hypothalamic peptide that stimulates the synthesis and secretion of GH
      from pituitary somatotroph cells. The GHRH receptor is a seven-transmembrane G
      protein-coupled receptor that localizes to the surface of somatotroph cells and
      binds GHRH. Alternative splicing of the GHRH receptor primary transcript at the
      intron/exon boundary 3' of exon 11 results in inclusion of sequence that is
      normally intronic. In the human, this inclusion has an in-frame premature stop
      codon, and this variant mRNA encodes a protein truncated just before the sixth
      transmembrane domain. To identify the effects of the truncated receptor on
      signaling of the wild-type receptor and the mechanisms by which its effects are
      produced, the full-length and truncated receptor constructs were epitope tagged
      and transfected into HeLa T4 cells to examine signaling and expression. Results
      show that the truncated GHRH receptor cannot signal through the cAMP pathway and
      acts as a dominant inhibitor of wild-type receptor signaling. The wild-type and
      truncated GHRH receptor proteins form a complex. Stably transfected cell lines
      were generated to examine the mechanism of signal inhibition by the truncated
      receptor. The data show that receptor cell surface expression is not altered when
      the wild-type and truncated receptors are cotransfected, but that truncated
      receptor coexpression substantially reduces GHRH binding by the wild-type
      receptor. The results support an important role for alternative splicing in
      mediating the effects of G protein-coupled receptors in general, and suggest that
      the GHRH receptor can form multimers, which may be important to its signaling
      properties.

PMID- 16423870
TI  - Autocrine growth hormone prevents lactogenic differentiation of mouse mammary
      epithelial cells.
AB  - We have examined the expression, postnatal ontogeny, and localization of mouse GH
      (mGH) and its relative expression during pregnancy, lactation, and weaning in the
      mouse. mGH mRNA and protein was expressed predominantly in the epithelial
      component of the mammary gland, and maximal expression was observed during the
      pubertal period. Autocrine mGH expression dramatically decreased during late
      pregnancy and lactation. Concordantly, autocrine mGH expression is repressed
      during forced differentiation of mouse HC11 mammary epithelial cells in culture.
      Forced expression of mGH in HC11 cells abrogated lactogenic differentiation as
      indicated by reduced expression of beta-casein and reduced expression and loss of
      lateral epithelial localization of E-cadherin. Forced expression of mGH in mouse
      mammary epithelial cells increased cell survival and proliferation and
      consequently increased the size of mammary acinar-like structures formed in three
      dimensional Matrigel. Thus, autocrine mGH expression in the mouse mammary
      epithelial cell is maximal at puberty and prevents mammary epithelial cell
      differentiation. Autocrine GH will therefore participate in mammary morphogenic
      processes at puberty.

PMID- 16423872
TI  - Patients enrolled in coronary intervention trials are not representative of
      patients in clinical practice: results from the Euro Heart Survey on Coronary
      Revascularization.
AB  - AIMS: Revascularization in patients with coronary artery disease changed over the
      last two decades, favouring the number of patients treated by means of
      percutaneous coronary interventions (PCI) when compared with coronary artery
      bypass grafting (CABG). Many randomized controlled trials (RCTs) have been
      performed to compare these two competing revascularization techniques. Because of
      the strict enrolment criteria of RCTs in which highly selected patients are
      recruited, the applicability of the results may be limited in clinical practice.
      The current study evaluates to what extent patients in clinical practice were
      similar to those who participated in RCTs comparing PCI with CABG. METHODS AND
      RESULTS: Clinical characteristics and 1-year outcome of 4713 patients enrolled in
      the Euro Heart Survey on Coronary Revascularization were compared with 8647
      patients who participated in 14 major RCTs, comparing PCI with CABG. In addition,
      we analysed which proportion of survey patients would have disqualified for trial
      participation (n=3033, 64%), aiming at identifying differences between trial
      eligible and trial-ineligible survey patients. In general, important differences
      were observed between trial participants and survey patients. Patients in
      clinical practice were older, more often had comorbid conditions, single-vessel
      disease, and left main stem stenosis when compared with trial participants.
      Almost identical differences were observed between trial-eligible and trial
      ineligible survey patients. In clinical practice, PCI was the treatment of
      choice, even in patients who were trial-ineligible (46% PCI, 26% CABG, 28%
      medical). PCI remained the preferred treatment option in patients with multi
      vessel disease (57% in trial-eligible and 40% in trial-ineligible patients,
      respectively, P<0.001); yet, the risk profile of patients treated by PCI was
      better than that for patients treated either by CABG or by medical therapy. In
      the RCTs, there was no mortality difference between PCI and CABG. In clinical
      practice, however, we observed 1-year unadjusted survival benefit for PCI vs.
      CABG (2.9 vs. 5.4%, P<0.001). Survival benefit was only observed in trial
      ineligible patients (3.3 vs. 6.2%, P<0.001). CONCLUSION: Many patients in
      clinical practice were not represented in RCTs. Moreover, only 36% of these
      patients were considered eligible for participating in a trial comparing PCI with
      CABG. We demonstrated that RCTs included younger patients with a better
      cardiovascular risk profile when compared with patients in everyday clinical
      practice. This study highlights the disparity between patients in clinical
      practice and patients in whom the studies that provide the evidence for treatment
      guidelines are performed.

PMID- 16423873
TI  - Emergency revascularization in patients with cardiogenic shock on admission: a
      report from the SHOCK trial and registry.
AB  - AIMS: To determine clinical correlates and optimal treatment strategy in patients
      with cardiogenic shock (CS) on admission. METHODS AND RESULTS: In SHould we
      emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) trial
      and registry patients with left ventricular (LV) dysfunction (n=1053), CS on
      admission occurred in 26% of directly admitted patients (n=166/627). Time from
      myocardial infarction to CS was shorter, initial haemodynamic profile poorer, and
      aggressive treatment less frequent in CS on admission than in delayed CS
      patients. CS on admission patients constituted a smaller relative proportion
      (11%) of the transferred (n=48/426) when compared with the directly admitted
      cohort (P<0.001). In-hospital mortality was higher (75 vs. 56%; P<0.001) with
      more rapid death (24-h mortality 40 vs. 17%; P<0.001) in CS on admission than in
      delayed CS patients. Emergency revascularization reduced in-hospital mortality in
      CS on admission (60 vs. 82%; P=0.001) and in delayed CS patients similarly (46
      vs. 62%; P<0.001; interaction P=0.25). After adjustment for clinical differences,
      CS on admission was an independent predictor of in-hospital mortality (P=0.008).
      CONCLUSION: CS on admission patients have a worse outcome but benefit equally
      from emergency revascularization as delayed CS patients, emphasizing the need for
      rapid and direct access of CS on admission patients to facilities providing this
      care.

PMID- 16423874
TI  - An engineered VEGF-activating zinc finger protein transcription factor improves
      blood flow and limb salvage in advanced-age mice.
AB  - Advances in understanding the relationship between protein structure and DNA
      binding specificity have made it possible to engineer zinc finger protein (ZFP)
      transcription factors to specifically activate or repress virtually any gene. To
      evaluate the potential clinical utility of this approach for peripheral vascular
      disease, we investigated the ability of an engineered vascular endothelial growth
      factor (VEGFa)-activating ZFP (MVZ+426b) to induce angiogenesis and rescue
      hindlimb ischemia in a murine model. Hindlimb ischemia was surgically induced in
      advanced-age C57/BL6 mice. Adenovirus (Ad) encoding either MVZ+426b or the
      fluorescent marker dsRed was delivered to the adducter muscle of the ischemic
      hindlimb, and the effects on blood flow, limb salvage, and vascularization were
      assessed. Ad-MVZ+426b induced expression of VEGFa at the mRNA and protein levels
      and stimulated a significant increase in vessel counts in the ischemic limb. This
      was accompanied by significantly increased blood flow and limb salvage as
      measured serially for 4 wk. These data demonstrate that activation of the
      endogenous VEGFa gene by an engineered ZFP can induce angiogenesis in a
      clinically relevant model and further document the feasibility of designing ZFPs
      to therapeutically regulate gene expression in vivo.

PMID- 16423875
TI  - Transcriptional profiling of myostatin-knockout mice implicates Wnt signaling in
      postnatal skeletal muscle growth and hypertrophy.
AB  - Myostatin is an inhibitor of skeletal muscle growth. Disruption of the Mstn gene
      in mice results in muscles that weigh two to three times those of controls, but
      precisely how myostatin signals to exert its effects on muscle is unclear. We
      used the Affymetrix GeneChip system to identify differences in gene expression
      between myostatin null and wild-type mice. The results indicated a switch in
      muscle fiber type, from slow to fast, in the absence of myostatin. They also
      indicated that myostatin may act upstream of Wnt pathway components. Notably, it
      repressed expression of Wnt4. Wnt4 was capable of stimulating satellite cell
      proliferation, while inhibition of Wnt signaling down-regulated satellite cell
      proliferation. This evidence points to a role for Wnt/calcium signaling in the
      growth and maintenance of postnatal skeletal muscle. This study offers new
      insight into potential downstream targets of myostatin, which will be beneficial
      for elucidation of the mechanism through which myostatin acts to inhibit muscle
      growth.

PMID- 16423876
TI  - Testosterone regulates FGF-2 expression during testis maturation by an IRES
      dependent translational mechanism.
AB  - Spermatogenesis is a complex process involving cell proliferation,
      differentiation, and apoptosis. Fibroblast growth factor 2 (FGF-2) is involved in
      testicular function, but its role in spermatogenesis has not been fully
      documented. The control of FGF-2 expression particularly occurs at the
      translational level, by an internal ribosome entry site (IRES)-dependent
      mechanism driving the use of alternative initiation codons. To study IRES
      activity regulation in vivo, we have developed transgenic mice expressing a
      bicistronic construct coding for two luciferase genes. Here, we show that the FGF
      2 IRES is age-dependently activated in mouse testis, whereas EMCV and c-myc IRESs
      are not. Real-time PCR confirms that this regulation is translational. By using
      immunohistological techniques, we demonstrate that FGF-2 IRES stimulation occurs
      in adult, but not in immature, type-A spermatogonias. This is correlated with
      activation of endogenous FGF-2 expression in spermatogonia; whereas FGF-2 mRNA
      transcription is known to decrease in adult testis. Interestingly, the FGF-2 IRES
      activation is triggered by testosterone and is partially inhibited by siRNA
      directed against the androgen receptor. Two-dimensional analysis of proteins
      bound to the FGF-2 mRNA 5'UTR after UV cross-linking reveals that testosterone
      treatment correlates with the binding of several proteins. These data suggest a
      paracrine loop where IRES-dependent FGF-2 expression, stimulated by Sertoli cells
      in response to testosterone produced by Leydig cells, would in turn activate
      Leydig function and testosterone production. In addition, nuclear FGF-2 isoforms
      could be involved in an intracrine function of FGF-2 in the start of
      spermatogenesis, mitosis, or meiosis initiation. This report demonstrates that
      mRNA translation regulation by an IRES-dependent mechanism participates in a
      physiological process.

PMID- 16423877
TI  - Proinflammatory cytokines released from microglia inhibit gap junctions in
      astrocytes: potentiation by beta-amyloid.
AB  - Brain inflammation is characterized by a reactive gliosis involving the
      activation of astrocytes and microglia. This process, common to many brain
      injuries and diseases, underlies important phenotypic changes in these two glial
      cell types. One characteristic feature of astrocytes is their high level of
      intercellular communication mediated by gap junctions. Previously, we have
      reported that astrocyte gap junctional communication (AGJC) and the expression of
      connexin 43 (Cx43), the main constitutive protein of gap junctions, are inhibited
      in microglia (MG)-astrocyte cocultures. Here, we report that bacterial
      lipopolysaccharide activation of microglia increases their inhibitory effect on
      Cx43 expression and AGJC. This inhibition is mimicked by treating astrocyte
      cultures with conditioned medium harvested from activated microglia. Interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were identified as
      being the main factors responsible for this conditioned medium-mediated activity.
      Interestingly, an inflammatory response characterized by MG activation and
      reactive astrocytes occurs in Alzheimer's disease, at sites of beta-amyloid
      (Abeta) deposits. We found that this peptide potentiates the inhibitory effect of
      a conditioned medium diluted at a concentration that is not effective per se.
      This potentiation is prevented by treating astrocytes with specific blockers of
      IL-1beta and TNF-alpha activities. Thus, the suppression of communication between
      astrocytes, induced by activated MG could contribute to the proposed role of
      reactive gliosis in this neurodegenerative disease.

PMID- 16423878
TI  - Retinal dysfunction in patients with chronic Chagas' disease is associated to
      anti-Trypanosoma cruzi antibodies that cross-react with rhodopsin.
AB  - To investigate retinal involvement in chronic Chagas' disease, we performed
      electroretinography and retinal fluorescein angiography studies in chagasic
      patients. Our results demonstrated a dissociated electrophysiological response
      characterized by both an abnormal reduction of the electroretinographic b-wave
      amplitude and a delayed latency, under the dark-adaptated condition. These
      alterations are compatible with a selective dysfunction of the rods. Antibodies
      raised against Trypanosoma cruzi that also interact with beta1-adrenergic
      receptor blocked light stimulation of cGMP-phosphodiesterase in bovine rod
      membranes. The specificity from the antibody-rhodopsin interaction was confirmed
      by Western blot analysis and antigenic competition experiments. Our results
      suggest an immunomediated rhodopsin blockade. T. cruzi infection probably induces
      an autoimmune response against rhodopsin in the chronic phase of Chagas' disease
      through a molecular mimicry mechanism similar to that described previously on
      cardiac human beta1-adrenergic and M2-cholinergic receptors, all related to the
      same subfamily of G-protein-coupled receptors.

PMID- 16423879
TI  - Lives and times of nuclear receptors.
AB  - Down-regulation of receptor in response to ligand was one of the earliest
      functional readouts of steroid hormone action. The loss of total receptor content
      upon stimulation, referred to initially as receptor "processing," was carefully
      described with respect to receptor nuclear transformation or tight nuclear
      binding. It was these early studies that were the first to note a correlation
      between receptor turnover and induction of gene transcription, leading to the
      proposal that down-regulation of receptor was involved in mechanisms of
      transcriptional activation. This idea has now attracted renewed attention with
      the discovery that ligand-induced "processing" in the form of proteolysis is
      carried out by the 26S proteasome, a multicatalytic enzyme whose activity is
      directly coupled to cell-cycle control, signal transduction, and importantly,
      transcription. Here, we review our current understanding of the mechanism and
      relevance of proteolysis to receptor function based on general concepts that have
      emerged from analyses of liganded members of the nuclear receptor family.

PMID- 16423880
TI  - Switching of NR5A proteins associated with the inhibin alpha-subunit gene
      promoter after activation of the gene in granulosa cells.
AB  - The inhibin alpha-subunit gene is transcriptionally activated by FSH in ovarian
      granulosa cells during follicular growth. We have investigated the roles of the
      NR5A family nuclear receptors steroidogenic factor 1 (SF-1) and liver receptor
      homolog 1 (LRH-1) in transcriptional activation of the inhibin alpha-subunit
      gene. Transfection assays using an inhibin alpha-subunit promoter reporter in
      GRMO2 granulosa cells show that LRH-1 and SF-1 act similarly to increase promoter
      activity, and that the activity of both transcription factors is augmented by the
      coactivators cAMP response element-binding protein-binding protein and steroid
      receptor coactivator 1. However, chromatin immunoprecipitation experiments
      illustrate differential dynamic association of LRH-1 and SF-1 with the alpha
      subunit inhibin promoter in both primary cells and the GRMO2 granulosa cell line
      such that hormonal stimulation of transcription results in an apparent
      replacement of SF-1 with LRH-1. Transcriptional stimulation of the inhibin alpha
      subunit gene is dependent on MAPK kinase activity, as is the dynamic
      association/disassociation of SF-1 and LRH-1 with the promoter. Inhibition of the
      phosphatidylinositol 3-kinase signaling pathway influences promoter occupancy and
      transcriptional activation by SF-1 but not LRH-1, suggesting a possible
      mechanistic basis for the distinct functions of these NR5A proteins in inhibin
      alpha-subunit gene regulation.

PMID- 16423881
TI  - Role of steroid receptor coactivators in glucocorticoid and transforming growth
      factor beta regulation of plasminogen activator inhibitor gene expression.
AB  - TGFbeta is a major regulator of extracellular matrix deposition and a potent
      inducer of type-1 plasminogen activator inhibitor (PAI-1) gene expression. We
      have reported that liganded glucocorticoid receptor (GR) represses TGFbeta
      transactivation of PAI-1 in Hep3B human hepatoma cells and that it interacts
      functionally and physically with the C-terminal activation domain of Smad3, a
      mediator of TGFbeta signaling. The ligand binding domain of GR is required for GR
      mediated transrepression, but the GR DNA binding domain and activation function 1
      domains are not. We report here that overexpression of steroid receptor
      coactivator-1 (SRC-1) and GR-interacting protein-1 (GRIP-1) enhanced repression
      by liganded GR, and by a GR mutant defective in repression. Surprisingly, SRC-1
      and GRIP-1 also enhanced TGFbeta-induced activation from the TGFbeta-responsive
      sequence of the PAI-1 gene by a GR-independent mechanism. Coimmunoprecipitation
      and mammalian one-hybrid experiments demonstrated that SRC-1 and GRIP-1 interact
      physically with endogenous Smad3 and functionally with the C-terminal domain of
      Smad3 to directly enhance transcription. Thus, the GR coactivators, SRC-1 and
      GRIP-1, act as both corepressors of the glucocorticoid repression of PAI-1 gene
      transcription, and coactivators of TGFbeta-induced activation of the PAI-1
      promoter.

PMID- 16423882
TI  - Suppression of androgen receptor signaling in prostate cancer cells by an
      inhibitory receptor variant.
AB  - There is increasing evidence that sensitization of the androgen receptor (AR)
      signaling pathway contributes to the failure of androgen ablation therapy for
      prostate cancer, and that direct targeting of the AR may be a useful therapeutic
      approach. To better understand how AR function could be abrogated in prostate
      cancer cells, we have developed a series of putative dominant-negative variants
      of the human AR, containing deletions or mutations in activation functions AF-1,
      AF-5, and/or AF-2. One construct, AR inhibitor (ARi)-410, containing a deletion
      of AF-1 and part of AF-5 of the AR, had no intrinsic transactivation activity but
      inhibited wild-type AR (wtAR) in a ligand-dependent manner by at least 95% when
      transfected at a 4:1 molar ratio. ARi-410 was an equally potent inhibitor of gain
      of-function AR variants. Ectopic expression of ARi-410 inhibited the
      proliferation of AR-positive LNCaP cells, but not AR-negative PC-3 cells. Whereas
      ARi-410 also marginally inhibited progesterone receptor activity, this was far
      less pronounced than the effect on AR (50% vs. 95% maximal inhibition,
      respectively), and there was no inhibition of either vitamin D or estrogen
      receptor activity. In the presence of ligand, ARi-410 interacted with wtAR, and
      both receptors translocated into the nucleus. Whereas the amino-carboxy terminal
      interaction was not necessary for optimal dominant-negative activity, disruption
      of dimerization through the ligand binding domain reduced the efficacy of ARi
      410. In addition, although inhibition of AR function by ARi-410 was not dependent
      on DNA binding, the DNA binding domain was required for dominant-negative
      activity. Taken together, our results suggest that interaction between ARi-410
      and the endogenous AR in prostate cancer cells, potentially through the DNA
      binding and ligand binding domains, results in a functionally significant
      reduction in AR signaling and AR-dependent cell growth.

PMID- 16423884
TI  - Subcutaneous lesions in dermatomyositis.

PMID- 16423883
TI  - The genomic analysis of the impact of steroid receptor coactivators ablation on
      hepatic metabolism.
AB  - Members of the steroid receptor coactivator (SRC) family, which include SRC-1
      (NcoA-1/p160), SRC-2(TIF2/GRIP1/NcoA-2) and SRC-3(pCIP/RAC3/ACTR/pCIP/
      AIB1/TRAM1), are critical mediators of steroid receptor action. Gene ablation
      studies previously identified SRC-1 and SRC-2 as being involved in the control of
      energy homeostasis. A more precise identification of the molecular pathways
      regulated by these coactivators is crucial for understanding the role of steroid
      receptor coactivators in the control of energy homeostasis and obesity. A genomic
      approach using microarray analysis was employed to identify the subsets of genes
      that are altered in the livers of SRC-1-/-, SRC-2-/-, and SRC-3-/- mice.
      Microarray analysis demonstrates that gene expression changes are specific and
      nonoverlapping for each SRC member in the liver. The overall pattern of altered
      gene expressions in the SRC-1-/- mice was up-regulation, whereas SRC-2-/- mice
      showed an overall down-regulation. Several key regulatory enzymes of energy
      metabolism were significantly altered in the liver of SRC-2-/- mice, which are
      consistent with the prior observation that SRC-2-/- mice have increased energy
      expenditure. This study demonstrates that the molecular targets of SRC-2
      regulation in the murine liver stimulate fatty acid degradation and glycolytic
      pathway, whereas fatty acid, cholesterol, and steroid biosynthetic pathways are
      down-regulated.

PMID- 16423885
TI  - Hypothenar hammer syndrome in a patient with rheumatoid arthritis: a mimic of
      vasculitis.

PMID- 16423886
TI  - Lack of association of MYO9B genetic variants with coeliac disease in a British
      cohort.
AB  - BACKGROUND AND AIMS: Development of coeliac disease involves an interaction
      between environmental factors (especially dietary wheat, rye, and barley
      antigens) and genetic factors (there is strong inherited disease susceptibility).
      The known human leucocyte antigen (HLA)-DQ2 and -DQ8 association explains only a
      minority of disease heritability. A recent study in the Dutch population
      suggested that genetic variation in the 3' region of myosin IXB (MYO9B)
      predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein
      involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to
      influence intestinal permeability and hence intestinal antigen presentation.
      METHODS: Four single nucleotide polymorphisms were chosen to tag all common
      haplotypes of the MYO9B 3' haplotype block (exons 15-27). We genotyped 375
      coeliac disease cases and 1366 controls (371 healthy and 995 population based).
      All individuals were of White UK Caucasian ethnicity. RESULTS: UK healthy control
      and population control allele frequencies were similar for all MYO9B variants.
      Case control analysis showed no significant association of any variant or
      haplotype with coeliac disease. CONCLUSIONS: Genetic variation in MYO9B does not
      have a major effect on coeliac disease susceptibility in the UK population.
      Differences between populations, a weaker effect size than originally described,
      or possibly a type I error in the Dutch study might explain these findings.

PMID- 16423887
TI  - Gastrointestinal Candida colonisation promotes sensitisation against food
      antigens by affecting the mucosal barrier in mice.
AB  - BACKGROUNDS AND AIMS: Controversy still exists as to whether gastrointestinal
      colonisation by Candida albicans contributes to aggravation of atopic dermatitis.
      We hypothesised that Candida colonisation promotes food allergy, which is known
      to contribute to a pathogenic response in atopic dermatitis. We tested this using
      a recently established murine Candida colonisation model. METHODS: Candida
      colonisation in the gastrointestinal tract was established by intragastric
      inoculation with C albicans in mice fed a synthetic diet. To investigate
      sensitisation against food antigen, mice were intragastrically administered with
      ovalbumin every other day for nine weeks, and antiovalbumin antibody titres were
      measured weekly. To examine gastrointestinal permeation of food antigen, plasma
      concentrations of ovalbumin were measured following intragastric administration
      of ovalbumin. RESULTS: Ovalbumin specific IgG and IgE titres were higher in
      BALB/c mice with Candida colonisation than in normal mice. Gastrointestinal
      permeation of ovalbumin was enhanced by colonisation in BALB/c mice. Histological
      examination showed that colonisation promoted infiltration and degranulation of
      mast cells. Candida colonisation did not enhance ovalbumin permeation in mast
      cell deficient W/Wv mice but did in congenic littermate control +/+ mice.
      Reconstitution of mast cells in W/Wv mice by transplantation of bone marrow
      derived mast cells restored the ability to increase ovalbumin permeation in
      response to Candida colonisation. CONCLUSIONS: These results suggest that
      gastrointestinal Candida colonisation promotes sensitisation against food
      antigens, at least partly due to mast cell mediated hyperpermeability in the
      gastrointestinal mucosa of mice.

PMID- 16423889
TI  - Wotherspoon criteria combined with B cell clonality analysis by advanced
      polymerase chain reaction technology discriminates covert gastric marginal zone
      lymphoma from chronic gastritis.
AB  - BACKGROUND AND AIMS: Gastric mucosa associated lymphoid tissue lymphoma is a well
      defined B cell lymphoma yet often impossible to distinguish from severe chronic
      gastritis on morphological grounds alone. Therefore, it was suggested to use the
      clonality of the immunoglobulin (Ig) heavy chain (H) genes, as detected by
      polymerase chain reaction (PCR), as a decisive criterion. However, there is
      controversy as to whether B cell clonality also exists in chronic gastritis,
      hence rendering this approach futile at present. METHODS: An expert panel re
      examined the histology and immunohistochemistry of a total of 97 cases of gastric
      biopsies, including clearcut marginal zone lymphoma, chronic gastritis, and
      ambiguous cases, applying the Wotherspoon criteria on the basis of haematoxylin
      eosin and CD20 immunostainings. In addition, a new and advanced PCR system for
      detection of clonal IgH gene rearrangements was independently applied in two
      institutions in each case. RESULTS: The overall IgH clonality assessments of both
      institutions were in total agreement. Overt lymphoma (Wotherspoon score 5) was
      clonal in 24/26 cases. Chronic gastritis (Wotherspoon scores 1 and 2) was not
      clonal in 52/53 cases; the clonal case being Wotherspoon score 2. Of 18 cases
      with ambiguous histology (Wotherspoon scores 3 and 4) four were clonal.
      CONCLUSIONS: Using advanced PCR technology, clonal gastritis is extremely rare,
      if it exists at all. Thus B cell clonality in Wotherspoon 3 and 4 cases is
      regarded as suitable for definitively diagnosing gastric marginal zone lymphoma.

PMID- 16423888
TI  - Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to
      apoptosis as a mechanism of progressive hepatic fibrogenesis in humans.
AB  - BACKGROUND AND AIMS: Myofibroblast-like cells, originating from activation of
      hepatic stellate cells (HSC/MFs), play a key role in liver fibrosis, a
      potentially reversible process that may rely on induction of HSC/MFs apoptosis.
      While this possibility has been shown in cultured rat HSC, very limited data are
      currently available for human HSC/MFs. METHODS: Cultured human HSC/MFs were
      exposed to several proapoptotic stimuli, including those known to induce
      apoptosis in rat HSC/MFs, and induction of cell death and related mechanisms were
      investigated using morphology, molecular biology, and biochemical techniques.
      RESULTS: In this study we report that fully activated human HSC/MFs did not
      undergo spontaneous apoptosis and survived to prolonged serum deprivation, Fas
      activation, or exposure to nerve growth factor, tumour necrosis factor alpha (TNF
      alpha), oxidative stress mediators, doxorubicin, and etoposide. Induction of
      caspase dependent, mitochondria driven apoptosis in HSC/MFs was observed only
      when protein synthesis or transcription were inhibited. Importantly, the process
      of HSC activation was accompanied by changes in expression of a set of genes
      involved in apoptosis control. In particular, activated human HSC/MFs in culture
      overexpressed Bcl-2. The role of Bcl-2 was crucial as Bcl-2 silenced cells became
      susceptible to TNF-alpha induced apoptosis. Finally, Bcl-2 was markedly expressed
      in HSC/MFs present in liver tissue obtained from patients with hepatitis C virus
      related cirrhosis. CONCLUSIONS: Human activated HSC/MFs are resistant to most
      proapoptotic stimuli due to Bcl-2 overexpression and this feature may play a key
      role in the progression of fibrosis in chronic liver diseases.

PMID- 16423890
TI  - Survival and cause specific mortality in patients with inflammatory bowel
      disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004.
AB  - BACKGROUND AND AIMS: We followed a population based cohort of patients with
      inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to
      analyse long term survival and cause specific mortality. MATERIAL AND METHODS: A
      total of 692 patients were followed for a median of 14 years. Standardised
      mortality ratios (SMRs, observed/expected deaths) were calculated for specific
      causes of death. Cox proportional hazards regression was used to determine if
      clinical variables were independently associated with mortality. RESULTS: Fifty
      six of 314 Crohn's disease patients died compared with 46.0 expected (SMR 1.2
      (95% confidence interval (CI) 0.9-1.6)), and 62 of 378 ulcerative colitis (UC)
      patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6-1.0)). Eighteen
      patients with Crohn's disease (32%) died from disease related complications, and
      12 patients (19%) died from causes related to UC. In Crohn's disease, an
      increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95%
      CI 3.2-11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7-10.2)), and
      chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3-7.5)) was
      observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4-0.9)).
      Increased age at diagnosis and male sex were associated with mortality in both
      subtypes. In UC but not Crohn's disease, a diagnosis after 1980 was associated
      with decreased mortality. CONCLUSIONS: In this population based study of IBD
      patients from North America, overall survival was similar to that expected in the
      US White population. Crohn's disease patients were at increased risk of dying
      from gastrointestinal disease and COPD whereas UC patients had a decreased risk
      of cardiovascular death.

PMID- 16423892
TI  - Sporadic adenoma in ulcerative colitis: endoscopic resection is an adequate
      treatment.
AB  - BACKGROUND AND AIMS: In studies with small numbers of cases, it has been shown
      that endoscopic resection of adenomas in ulcerative colitis represents adequate
      treatment. In a larger study cohort with more prolonged follow up, we assessed
      the reliability of this finding. METHODS: Between 1988 and 2002, 148 consecutive
      patients, mainly from private gastroenterologists' practices, with ulcerative
      colitis were diagnosed as having an adenoma. In 60 patients, histological
      diagnosis was established in biopsies and in 87 patients in polypectomy
      specimens; one patient underwent proctocolectomy following diagnosis. The outcome
      of these patients was analysed after a mean follow up period of 6.0 (3.63) years.
      RESULTS: Among 60 patients, surprisingly without endoscopic treatment, 48.3%
      developed ulcerative colitis associated neoplasia in the same colon segment
      (23.3% low grade intraepithelial neoplasia; 8.3% high grade intraepithelial
      neoplasia; 16.7% carcinoma). Among 87 patients undergoing polypectomy of the
      adenoma, follow up revealed colitis associated neoplasia in other segments of
      colon in 4.6% of cases. CONCLUSION: Development of adenocarcinomas in a total of
      6.7% of the overall patient group, and in 2.3% of those undergoing polypectomy,
      indicates that biopsy based diagnosis of an adenoma in ulcerative colitis must be
      considered to mandate endoscopic resection of the lesion; 40% of affected
      patients did not receive any form of endoscopic removal of the lesion. This shows
      that the most recent guidelines are not followed in a considerable number of
      patients with ulcerative colitis in private practice in Germany. Although
      polypectomy of the adenoma represents adequate therapy, further regular follow up
      examinations are nevertheless necessary.

PMID- 16423891
TI  - Neural contractions in colonic strips from patients with diverticular disease:
      role of endocannabinoids and substance P.
AB  - BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely defined
      pathogenesis. Motor abnormalities of the intestinal wall have been frequently
      described but very little is known about their mechanisms. We investigated in
      vitro the neural response of colonic longitudinal muscle strips from patients
      undergoing surgery for complicated diverticular disease (diverticulitis).
      METHODS: The neural contractile response to electrical field stimulation of
      longitudinal muscle strips from the colon of patients undergoing surgery for
      colonic cancer or diverticulitis was challenged by different receptor agonists
      and antagonists. RESULTS: Contractions of colonic strips from healthy controls
      and diverticulitis specimens were abolished by atropine. The beta adrenergic
      agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had
      similar potency in reducing the electrical twitch response in controls and
      diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100
      times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in
      diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1
      receptor, had no intrinsic activity in control preparations but potentiated the
      neural twitch in diseased tissues by up to 196% in a concentration dependent
      manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips
      but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular
      disease patients. Colonic levels of the endogenous ligand of cannabinoid and
      vanilloid TRPV1 receptors anandamide were more than twice those of control
      tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had
      opposite effects in the two preparations, completely inhibiting the contractions
      of control strips but potentiating those in diverticular preparations, an effect
      selectively inhibited by SR140333. CONCLUSIONS: Neural control of colon motility
      is profoundly altered in patients with diverticulitis. Their raised levels of
      anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1
      receptor, and the SR141716 induced intrinsic response, suggest that
      endocannabinoids may be involved in the pathophysiology of complications of
      colonic diverticular disease.

PMID- 16423893
TI  - A multifunctional cytoprotective agent that reduces neurodegeneration after
      ischemia.
AB  - Cellular and molecular pathways underlying ischemic neurotoxicity are
      multifaceted and complex. Although many potentially neuroprotective agents have
      been investigated, the simplicity of their protective mechanisms has often
      resulted in insufficient clinical utility. We describe a previously
      uncharacterized class of potent neuroprotective compounds, represented by PAN
      811, that effectively block both ischemic and hypoxic neurotoxicity. PAN-811
      disrupts neurotoxic pathways by at least two modes of action. It causes a
      reduction of intracellular-free calcium as well as free radical scavenging
      resulting in a significant decrease in necrotic and apoptotic cell death. In a
      rat model of ischemic stroke, administration of PAN-811 i.c.v. 1 h after middle
      cerebral artery occlusion resulted in a 59% reduction in the volume of
      infarction. Human trials of PAN-811 for an unrelated indication have established
      a favorable safety and pharmacodynamic profile within the dose range required for
      neuroprotection warranting its clinical trial as a neuroprotective drug.

PMID- 16423894
TI  - Intrinsic backbone preferences are fully present in blocked amino acids.
AB  - The preferences of amino acid residues for ,psi backbone angles vary strikingly
      among the amino acids, as shown by the backbone angle found from the
      (3)J(H(alpha),H(N)) coupling constant for short peptides in water. New data for
      the (3)J(H(alpha),H(N)) values of blocked amino acids (dipeptides) are given
      here. Dipeptides exhibit the full range of coupling constants shown by longer
      peptides such as GGXGG and dipeptides present the simplest system for analyzing
      backbone preferences. The dipeptide coupling constants are surprisingly close to
      values computed from the coil library (conformations of residues not in helices
      and not in sheets). Published coupling constants for GGXGG peptides agree closely
      with dipeptide values for all nonpolar residues and for some polar residues but
      not for X = D, N, T, and Y, which are probably affected by polar side chain
      backbone interactions in GGXGG peptides. Thus, intrinsic backbone preferences are
      already determined at the dipeptide level and remain almost unchanged in GGXGG
      peptides and are strikingly similar in the coil library of conformations from
      protein structures. The simplest explanation for the backbone preferences is that
      backbone conformations are strongly affected by electrostatic dipole-dipole
      interactions in the peptide backbone and by screening of these interactions with
      water, which depends on nearby side chains. Strong backbone electrostatic
      interactions occur in dipeptides. This is shown by calculations both of backbone
      electrostatic energy for different conformers of the alanine dipeptide in the gas
      phase and by electrostatic solvation free energies of amino acid dipeptides.

PMID- 16423895
TI  - Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha.
AB  - Estrogen is known to influence glucose homeostasis with dominant effects in the
      liver, but the role of estrogen receptors in muscle glucose metabolism is
      unknown. In the present study, we investigated the expression of the two estrogen
      receptors, ERalpha and ERbeta, and their influence on regulation of the glucose
      transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse
      gastrocnemius muscle. Immunohistochemical analysis revealed that ERalpha and
      ERbeta are coexpressed in the nuclei of most muscle cells, and that their levels
      were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice].
      GLUT4 expression on the muscle cell membrane was not affected by loss of ERbeta
      but was extremely reduced in ERalpha(-/-) mice and elevated in ArKO mice. RT-PCR
      confirmed a parallel reduction in GLUT4 mRNA levels in ERalpha(-/-) mice. Upon
      treatment of ArKO mice with the ERbeta agonist 2,3-bis(4
      hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence
      and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in
      ERbeta(-/-) and ERalpha(-/-) mice than in WT littermates. GLUT4 and caveolin-1
      were colocalized in WT and ArKO mice but not in ERbeta(-/-) and ERalpha(-/-)
      mice. These results reveal that ERalpha is a positive regulator of GLUT4
      expression, whereas ERbeta has a suppressive role. Both ERbeta and ERalpha are
      necessary for optimal caveolin-1 expression. Taken together, these results
      indicate that colocalization of caveolin-1 and GLUT4 is not an absolute
      requirement for muscle glucose metabolism but that reduction in GLUT4 could be
      contributing to the insulin resistance observed in ERalpha(-/-) mice.

PMID- 16423896
TI  - Leptin: a potential novel antidepressant.
AB  - Leptin, a hormone secreted from adipose tissue, was originally discovered to
      regulate body weight. The localization of the leptin receptor in limbic
      structures suggests a potential role for leptin in emotional processes. Here, we
      show that rats exposed to chronic unpredictable stress and chronic social defeat
      exhibit low leptin levels in plasma. Systemic leptin treatment reversed the
      hedonic-like deficit induced by chronic unpredictable stress and improved
      behavioral despair dose-dependently in the forced swim test (FST), a model widely
      used for screening potential antidepressant efficacy. The behavioral effects of
      leptin in the FST were accompanied by increased neuronal activation in limbic
      structures, particularly in the hippocampus. Intrahippocampal infusion of leptin
      produced a similar antidepressant-like effect in the FST as its systemic
      administration. By contrast, infusion of leptin into the hypothalamus decreased
      body weight but had no effect on FST behavior. These findings suggest that: (i)
      impaired leptin production and secretion may contribute to chronic stress-induced
      depression-like phenotypes, (ii) the hippocampus is a brain site mediating
      leptin's antidepressant-like activity, and (iii) elevating leptin signaling in
      brain may represent a novel approach for the treatment of depressive disorders.

PMID- 16423897
TI  - Organization of spines on the dendrites of Purkinje cells.
AB  - Dendritic spines have been investigated intensively over recent years; however,
      little is yet known about how they organize on the cell surface to make synaptic
      contacts with appropriate axons. Here we investigate spine distributions along
      the distal dendrites of cerebellar Purkinje cells, after biolistic labeling of
      intact tissue with a lipid-soluble dye. We show that the spines have a preference
      to form regular linear arrays and to trace short-pitch helical paths. The helical
      ordering is not determined by external factors that may influence how individual
      spines develop, because the same periodicities were present in fish and mammalian
      Purkinje cells, including those of weaver mice, which are depleted of the normal
      presynaptic partners for the spines. The ordering, therefore, is most likely an
      inherent property of the dendrite. Image reconstruction of dendrites from the
      different tissues showed that the helical spine distributions invariably lead to
      approximately equal sampling of surrounding space by the spineheads. The purpose
      of this organization may therefore be to maximize the opportunity of different
      spines to interact with different axons.

PMID- 16423899
TI  - Photocatalysis and the origin of life: synthesis of nucleoside bases from
      formamide on TiO2(001) single surfaces.
AB  - We report the conversion of a large fraction of formamide (NH(2)CHO) to high
      molecular-weight compounds attributed to nucleoside bases on the surface of a
      TiO(2) (001) single crystal in ultra-high vacuum conditions. If true, we present
      previously unreported evidence for making biologically relevant molecules from a
      C1 compound on any single crystal surface in high vacuum and in dry conditions.
      An UV light of 3.2 eV was necessary to make the reaction. This UV light excites
      the semiconductor surface but not directly the adsorbed formamide molecules or
      the reaction products. There thus is no need to use high energy in the form of
      photons or electrical discharge to make the carbon-carbon and carbon-nitrogen
      bonds necessary for life. Consequently, the reaction products may accumulate with
      time and may not be subject to decomposition by the excitation source. The
      formation of these molecules, by surface reaction of formamide, is proof that
      some minerals in the form of oxide semiconductors are active materials for making
      high-molecular-weight organic molecules that may have acted as precursors for
      biological compounds required for life in the universe.

PMID- 16423898
TI  - Structural insights into a protein-bound iron-molybdenum cofactor precursor.
AB  - The iron-molybdenum cofactor (FeMoco) of the nitrogenase MoFe protein is a highly
      complex metallocluster that provides the catalytically essential site for
      biological nitrogen fixation. FeMoco is assembled outside the MoFe protein in a
      stepwise process requiring several components, including NifB-co, an iron- and
      sulfur-containing FeMoco precursor, and NifEN, an intermediary assembly protein
      on which NifB-co is presumably converted to FeMoco. Through the comparison of
      Azotobacter vinelandii strains expressing the NifEN protein in the presence or
      absence of the nifB gene, the structure of a NifEN-bound FeMoco precursor has
      been analyzed by x-ray absorption spectroscopy. The results provide physical
      evidence to support a mechanism for FeMoco biosynthesis. The NifEN-bound
      precursor is found to be a molybdenum-free analog of FeMoco and not one of the
      more commonly suggested cluster types based on a standard [4Fe-4S] architecture.
      A facile scheme by which FeMoco and alternative, non-molybdenum-containing
      nitrogenase cofactors are constructed from this common precursor is presented
      that has important implications for the biosynthesis and biomimetic chemical
      synthesis of FeMoco.

PMID- 16423900
TI  - Cyclodextrin-covered organic nanotubes derived from self-assembly of dendrons and
      their supramolecular transformation.
AB  - The dendritic building blocks with a focal pyrene unit self-organize into
      vesicles in aqueous phase. The in situ inclusion of the focal pyrene units into
      the cavity of beta- or gamma-cyclodextrin (CD) induces self-assembled organic
      nanotubes with an average outer diameter of approximately 45 nm and inner
      diameter of 22 nm. The surface of the nanotube is covered with CD. Therefore, the
      functional group on the surface of the nanotube is controlled simply by modifying
      the functionality of CD. The removal of CD from the nanotube with poly(propylene
      glycol) reversibly generates vesicles. This work provides an efficient
      methodology not only to create an additional class of CD-covered organic
      nanotubes but also to exhibit reversible transformation of nanotubes and vesicles
      triggered by the motifs of dendron self-assembly, CD inclusion, and
      pseudorotaxane formation.

PMID- 16423901
TI  - Amplicon DNA melting analysis for mutation scanning and genotyping: cross
      platform comparison of instruments and dyes.
AB  - BACKGROUND: DNA melting analysis for genotyping and mutation scanning of PCR
      products by use of high-resolution instruments with special "saturation" dyes has
      recently been reported. The comparative performance of other instruments and dyes
      has not been evaluated. METHODS: A 110-bp fragment of the beta-globin gene
      including the sickle cell anemia locus (A17T) was amplified by PCR in the
      presence of either the saturating DNA dye, LCGreen Plus, or SYBR Green I.
      Amplicons of 3 different genotypes (wild-type, heterozygous, and homozygous
      mutants) were melted on 9 different instruments (ABI 7000 and 7900HT, Bio-Rad
      iCycler, Cepheid SmartCycler, Corbett Rotor-Gene 3000, Idaho Technology HR-1 and
      LightScanner, and the Roche LightCycler 1.2 and LightCycler 2.0) at a rate of 0.1
      degrees C/s or as recommended by the manufacturer. The ability of each
      instrument/dye combination to genotype by melting temperature (Tm) and to scan
      for heterozygotes by curve shape was evaluated. RESULTS: Resolution varied
      greatly among instruments with a 15-fold difference in Tm SD (0.018 to 0.274
      degrees C) and a 19-fold (LCGreen Plus) or 33-fold (SYBR Green I) difference in
      the signal-to-noise ratio. These factors limit the ability of most instruments to
      accurately genotype single-nucleotide polymorphisms by amplicon melting. Plate
      instruments (96-well) showed the greatest variance with spatial differences
      across the plates. Either SYBR Green I or LCGreen Plus could be used for
      genotyping by T(m), but only LCGreen Plus was useful for heterozygote scanning.
      However, LCGreen Plus could not be used on instruments with an argon laser
      because of spectral mismatch. All instruments compatible with LCGreen Plus were
      able to detect heterozygotes by altered melting curve shape. However, instruments
      specifically designed for high-resolution melting displayed the least variation,
      suggesting better scanning sensitivity and specificity. CONCLUSION: Different
      instruments and dyes vary widely in their ability to genotype homozygous variants
      and scan for heterozygotes by whole-amplicon melting analysis.

PMID- 16423902
TI  - Semiautomated method for determination of serum paraoxonase activity using
      paraoxon as substrate.
AB  - BACKGROUND: Serum paraoxonase (PON1) is an enzyme associated with HDL, and its
      ability to protect LDL from oxidation is one mechanism by which HDL protects
      against atherosclerosis. Low concentrations of PON1 are found in patients with
      type 2 diabetes or coronary heart disease. Serum PON1 activity may also be
      important in avoidance of organophosphate toxicity in industry. METHODS: The
      generally accepted method for determining PON1 activity requires use of a
      recording spectrophotometer and is not suited to large numbers of samples; in
      addition, automation presents particular problems because of the extreme toxicity
      of substrates such as paraoxon. We established a relatively safe microtiter plate
      method that facilitates the determination of PON1 activity at a rate of 120
      samples per hour. RESULTS: PON1 activity was determined by the generally accepted
      method (x) and the new method (y); results correlated with a slope close to unity
      (y = 0.93x + 8; r = 0.97; P < 0.0001; n = 101). Examination of differences by
      Bland-Altman plots showed a weak concentration-dependent difference (r = 0.33; P
      < 0.0001; n = 101). The intra- and interassay sample CVs, obtained with samples
      with PON1 activities ranging from 41 to 348 nmol x min(-1) x mL(-1), were 3.5%
      and 2.7%, respectively (n = 16). CONCLUSION: The proposed method for
      determination of PON1 activity is simple, relatively safe, and inexpensive and is
      suitable for analysis of large numbers of samples.

PMID- 16423903
TI  - Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential
      screening and prognostic tool.
AB  - BACKGROUND: Evaluation of tumor-specific circulating DNA in plasma/serum is a
      promising noninvasive diagnostic and prognostic tool requiring only a blood
      sample, which circumvents the logistic difficulties associated with the use of
      invasive procedures for serial tumor samplings during screening of lung cancer.
      METHODS: We reviewed English-language reports published in the MEDLINE database
      that provided the results of qualitative and quantitative studies on circulating
      DNA in serum/plasma of lung cancer patients. We searched the bibliographies of
      the retrieved reports and reviews. Abstracts presented at the 2003, 2004, and
      2005 annual meetings of the American Society of Clinical Oncology were also
      reviewed. RESULTS: More than 80 citations were retrieved, of which 33 met our
      criteria: 22 qualitative studies, and 11 quantitative studies. The studies varied
      in the choice of markers, frequency of alterations, sensitivities of used
      methodologies, sample sizes, treatment protocols, and prognostic correlates
      evaluated. CONCLUSIONS: The findings from the studies on serum/plasma DNA suggest
      that it would be possible to develop a simple blood test with high sensitivity
      and specificity that has potential for screening of high-risk individuals, for
      prognostic or staging purposes, and to be used as intermediate end-points of
      efficacy in chemo-prevention and therapeutic trials. However, further work is
      needed to identify additional biomarkers and to standardize present techniques
      for sample collection, processing, and analysis. Large prospective studies with
      long follow-ups are essential to eventually integrate blood marker-based assays
      into the clinical setting.

PMID- 16423904
TI  - Adipocyte fatty acid-binding protein is a plasma biomarker closely associated
      with obesity and metabolic syndrome.
AB  - BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) is traditionally
      thought to be a cytosolic fatty acid chaperone expressed in adipocytes. Mice with
      targeted disruption of the A-FABP gene exhibit a striking phenotype with strong
      protection from insulin resistance, hyperglycemia, and atherosclerosis. The
      clinical relevance of these findings remains to be confirmed. METHODS: We used
      tandem mass spectrometry-based proteomic analysis to identify proteins secreted
      from adipocytes and present in human serum. We measured serum A-FABP
      concentrations in 229 persons (121 men and 108 women; age range, 33-72 years),
      including 100 lean [body mass index (BMI) <25 kg/m2] and 129 overweight/obese
      individuals (BMI >25 kg/m2) selected from a previous cross-sectional study.
      RESULTS: A-FABP was released from adipocytes and was abundantly present in human
      serum. Mean (SD) circulating concentrations of A-FABP were significantly higher
      in overweight/obese than in lean persons [32.3 (14.8) vs 20.0 (9.8) microg/L; P <
      0.001]. Age- and sex-adjusted serum A-FABP concentrations correlated positively
      (P < 0.005) with waist circumference, blood pressure, dyslipidemia, fasting
      insulin, and the homeostasis model assessment insulin resistance index. Moreover,
      we observed a significant increase in A-FABP concentrations corresponding with
      increases in the number of components of the metabolic syndrome (P < 0.05).
      CONCLUSIONS: A-FABP is a circulating biomarker closely associated with obesity
      and components of the metabolic syndrome, and measurement of serum concentrations
      of A-FABP might be useful for clinical diagnosis of obesity-related metabolic and
      cardiovascular disorders.

PMID- 16423905
TI  - Isolated mitochondrial long-chain ketoacyl-CoA thiolase deficiency resulting from
      mutations in the HADHB gene.
AB  - BACKGROUND: The human mitochondrial trifunctional protein (MTP) complex is
      composed of 4 hydroacyl-CoA dehydrogenase-alpha (HADHA) and 4 hydroacyl-CoA
      dehydrogenase-beta (HADHB) subunits, which catalyze the last 3 steps in the fatty
      acid beta-oxidation spiral of long-chain fatty acids. The HADHB gene encodes long
      chain ketoacyl-CoA thiolase (LCTH) activity, whereas the HADHA gene contains the
      information for the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl
      CoA dehydrogenase (LCHAD) functions. At present, 2 different biochemical
      phenotypes of defects in the mitochondrial trifunctional protein complex are
      known: isolated LCHAD deficiency and generalized MTP deficiency, with decreased
      activities of all 3 enzymes. Isolated LCTH deficiency with mutations in the HADHB
      gene has not been reported. PATIENT AND RESULTS: We report a male newborn who
      presented with lactic acidosis, pulmonary edema, and cardiomyopathy leading to
      acute heart failure and death at the age of 6 weeks. Routine newborn screening by
      tandem mass spectrometry showed increased concentrations of the acylcarnitines
      tetradecenoylcarnitine, hexadecenoylcarnitine, hydroxypalmitoylcarnitine, and
      hydroxyoctadecenoylcarnitine, suggesting LCHAD deficiency or complete MTP
      deficiency. Enzyme investigations revealed very low LCTH (4% of normal) and
      normal LCHAD activities, whereas molecular analysis showed compound
      heterozygosity for 185G > A (R62H) and 1292T > C (F431S) mutations in the HADHB
      gene. CONCLUSION: We describe the first case of isolated LCTH deficiency based on
      a mutation in the HADHB gene.

PMID- 16423906
TI  - Serum proteomic fingerprints of adult patients with severe acute respiratory
      syndrome.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious
      disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns
      might be present in serum in response to the infection and could be useful for
      early detection of the disease. METHODS: Using surface-enhanced laser
      desorption/ionization (SELDI) ProteinChip technology, we profiled and compared
      serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS
      patients who were suspected cases during the SARS outbreak period. Proteomic
      patterns associated with SARS were identified by bioinformatic and biostatistical
      analyses. Features of interest were then purified and identified by tandem mass
      spectrometry. RESULTS: Twenty proteomic features were significantly different
      between the 2 groups. Fifteen were increased in the SARS group, and 5 were
      decreased. Their concentrations were correlated with 2 or more clinical and/or
      biochemical variables. Two were correlated with the SARS-CoV viral load.
      Hierarchical clustering analysis showed that a majority of the SARS patients
      (95%) had similar serum proteomic profiles and identified 2 subgroups with poor
      prognosis. ROC curve analysis identified individual features as potential
      biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). ROC curve
      areas were largest for an N-terminal fragment of complement C3c alpha chain (m/z
      28 119) and an internal fragment of fibrinogen alpha-E chain (m/z 5908).
      Immunoglobulin kappa light chain (m/z 24 505) positively correlated with viral
      load. CONCLUSIONS: Specific proteomic fingerprints in the sera of adult SARS
      patients could be used to identify SARS cases early during onset with high
      specificity and sensitivity.

PMID- 16423907
TI  - Determination of clopidogrel resistance by whole blood platelet aggregometry and
      inhibitors of the P2Y12 receptor.
AB  - BACKGROUND: Inhibition of platelet aggregation by clopidogrel may be insufficient
      in up to 30% of users. These nonresponders carry an increased risk of
      cardiovascular events. We reported here a simple assay to study clopidogrel
      responsiveness. METHODS: Electrical impedance aggregometry was performed in
      diluted whole blood in the presence of 5 and 20 micromol/L ADP. Some samples were
      incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (MeSAMP), a P2Y12
      receptor blocker, to maximize inhibition of aggregation before aggregometry. To
      validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244
      patients with coronary artery disease (CAD). RESULTS: At 5 micromol/L ADP, the
      imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was
      12.2 (2.2) Omega. The mean - 3 SD was used to define the cutoff for clopidogrel
      responsiveness: responders and nonresponders exhibited a 6-min impedance < or =5
      Omega and >5 Omega, respectively. Samples from nonresponders were incubated with
      MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic
      types of resistance. Sixteen percent of CAD patients were classified as
      nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance,
      respectively). Female sex was strongly associated with clopidogrel resistance (P
      = 0.0002, Fisher exact test). A higher clopidogrel loading dose (P = 0.0353, Mann
      Whitney U-test) was given to responders (median, 450 mg) than nonresponders
      (median, 300 mg). Age and cardiovascular diagnosis showed no significant
      associations. CONCLUSIONS: Impedance aggregometry using 5 mumol/L ADP is a useful
      tool for studying clopidogrel responsiveness. MeSAMP allows characterization of
      responsiveness "on treatment" and may be useful for optimizing clopidogrel
      dosing.

PMID- 16423908
TI  - Immunoassays developed for pregnancy-associated plasma protein-A (PAPP-A) in
      pregnancy may not recognize PAPP-A in acute coronary syndromes.
AB  - BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) concentrations are
      increased in the circulation of patients with acute coronary syndromes (ACS) and
      are associated with future adverse cardiac events. PAPP-A in ACS differs from
      PAPP-A in pregnancy in that PAPP-A in ACS is not complexed with the proform of
      eosinophil major basic protein (proMBP). We investigated the effect of antibody
      selection on the utility of PAPP-A assays for measurement of PAPP-A in pregnancy
      and/or ACS, and whether immunoassays for PAPP-A in pregnancy are suitable for
      PAPP-A in ACS. METHODS: We constructed 2-site sandwich time-resolved
      immunofluorometric assays using 22 monoclonal antibodies raised against pregnancy
      serum PAPP-A. All antibodies were studied in pairs, with each antibody used as
      either capture or tracer. We compared the reactivity of each antibody combination
      with PAPP-A/proMBP complex derived from pregnancy sera or with uncomplexed PAPP-A
      extracted from atherosclerotic plaques. Recombinant human PAPP-A and proMBP were
      also used to determine the specificity of the antibodies. We confirmed all major
      findings with serum samples collected from patients with myocardial infarction.
      RESULTS: Six monoclonal antibodies reacted with the proMBP subunit of the PAPP
      A/proMBP complex. Epitopes of 3 proMBP-reactive antibodies largely overlapped,
      but were well separated from those of another group of 3 proMBP-reactive
      antibodies. Assays using any of the 6 proMBP-reactive antibodies failed to detect
      PAPP-A in ACS. In addition, some 2-site assays capable of detecting PAPP-A in
      pregnancy were almost incapable of detecting PAPP-A in ACS, although the
      individual epitopes remained detectable in PAPP-A in ACS. CONCLUSIONS:
      Immunoassays developed for PAPP-A in pregnancy may not be suitable for PAPP-A in
      ACS. Assays for PAPP-A in ACS should be based on careful antibody selection and
      subjected to extensive testing with clinical ACS samples.

PMID- 16423909
TI  - Biological determinants of and reference values for plasma interleukin-8,
      monocyte chemoattractant protein-1, epidermal growth factor, and vascular
      endothelial growth factor: Results from the STANISLAS cohort.
AB  - BACKGROUND: Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1),
      epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) are
      known to be involved in various diseases related to inflammation, vascular
      remodeling, or growth deregulation. In addition, increases in plasma
      concentrations of these cytokines appear to provide useful diagnostic and
      prognostic information. We therefore investigated which factors most strongly
      influence the biological variations of plasma IL-8, MCP-1, EGF, and VEGF
      concentrations. METHODS: We used the Evidence biochip array analyzer to quantify
      plasma IL-8, MCP-1, EGF, and VEGF concentrations in a subsample of 304 children
      (age range, 4-17 years) and 540 adults (age range, 18-55 years) from the
      STANISLAS family study. We also calculated reference intervals for the 4
      cytokines. RESULTS: We found the following associations with plasma marker
      concentrations: Age, neutrophil count, and glucose concentration were positively
      associated with IL-8 concentrations in children and adults, as were smoking and
      platelet count in adults. MCP-1 concentrations were associated with age and
      smoking in both children and adults, monocyte count in children, and sex and
      hematocrit in adults. EGF concentrations were associated with platelet count in
      children and monocyte count and glucose in adults. VEGF concentrations were
      associated with age in children and adults and platelet count and alanine
      aminotransferase activity in adults. CONCLUSION: Our results for IL-8, MCP-1,
      EGF, and VEGF may be useful for interpretation of patients' laboratory results
      and for understanding the regulation of concentrations of these cytokines in
      physiologic conditions.

PMID- 16423913
TI  - Anterior cruciate ligament injuries in female athletes: Part 1, mechanisms and
      risk factors.
AB  - The mechanism underlying gender disparity in anterior cruciate ligament injury
      risk is likely multifactorial in nature. Several theories have been proposed to
      explain the mechanisms underlying the gender difference in anterior cruciate
      ligament injury rates. These theories include the intrinsic variables of
      anatomical, hormonal, neuromuscular, and biomechanical differences between
      genders and extrinsic variables. Identification of both extrinsic and intrinsic
      risk factors associated with the anterior cruciate ligament injury mechanism may
      provide direction for targeted prophylactic treatment to high-risk individuals.

PMID- 16423912
TI  - Getting back in the game.

PMID- 16423914
TI  - Comment: effect of fatigue on knee kinetics and kinematics in stop-jump tasks.

PMID- 16423915
TI  - Comment: effect of fatigue on knee kinetics and kinematics in stop-jump tasks.

PMID- 16423916
TI  - Comment: the effect of radiofrequency (RF) energy on human articular cartilage.

PMID- 16423917
TI  - Dr Hughston's legacy: a dedication to the fundamentals.

PMID- 16423918
TI  - Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives
      in experimental colitis.
AB  - Recent clinical trials of the gum resin of Boswellia serrata have shown promising
      results in patients with ulcerative colitis. The objective of this study was to
      determine whether a semisynthetic form of acetyl-11-keto-beta-boswellic acid
      (sAKBA), the most potent anti-inflammatory component of the resin, also confers
      protection in experimental murine colitis induced by dextran sodium sulfate (DSS)
      to compare its effects with those standard medications of ulcerative colitis like
      steroids and to examine whether leukocyte-endothelial cell adhesion is a major
      target of action of sAKBA. Clinical measurements of disease activity and
      histology were used to assess disease progression, and intravital microscopy was
      employed to monitor the adhesion of leukocytes and platelets in postcapillary
      venules of the inflamed colon. sAKBA treatment significantly blunted disease
      activity as assessed both grossly and by histology. Similarly, the recruitment of
      adherent leukocytes and platelets into inflamed colonic venules was profoundly
      reduced in mice treated with sAKBA. Because previous studies in the DSS model
      have shown that P-selectin mediates these blood cell-endothelial cell
      interactions, the expression of P-selectin in the colonic microcirculation was
      monitored using the dual-radiolabeled antibody technique. The treatment of
      established colitis with sAKBA largely prevented the P-selectin upregulation
      normally associated with DSS colitis. All of the protective responses observed
      with sAKBA were comparable to that realized in mice treated with a
      corticosteroid. Our findings demonstrated an anti-inflammatory effect of sAKBA
      and indicated that P-selectin-mediated recruitment of inflammatory cells is a
      major site of action for this novel anti-inflammatory agent.

PMID- 16423919
TI  - Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB
      1 and MCH receptor abundance.
AB  - Intact vagal afferent neurons are required for the satiety effects of the
      intestinal hormone cholecystokinin (CCK) and the orexigenic effects of the
      gastric regulatory peptide ghrelin. In this study, we examined the localization
      of ghrelin receptors in nodose ganglia and their function in regulating the
      expression of other orexigenic receptors, notably cannabinoid (CB)-1 and melanin
      concentrating hormone (MCH)-1 receptors. With the use of RT-PCR, transcripts
      corresponding to both functional [growth hormone secretagogue receptor (GHS-R)1a]
      and truncated forms (GHS-R1b) of the ghrelin receptor were detected in rat nodose
      ganglia. There was no difference in expression between rats fed ad libitum or
      fasted for up to 48 h. Immunohistochemical studies using antibodies directed at
      GHS-R1a revealed expression in over 75% of neurons also expressing CCK-1
      receptors in the mid- and caudal regions of the ganglion. There was also
      expression in human nodose ganglia. In fasted rats in which CB-1 and MCH-1
      receptor expression was increased, administration of ghrelin prevented the
      downregulation by refeeding. We conclude that the actions of CCK and ghrelin are
      mediated by a common population of vagal afferent neurons. Ghrelin may act to
      limit the action of CCK in depressing expression of CB-1 and MCH-1 receptors and
      other receptors.

PMID- 16423920
TI  - Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha
      OSTbeta in cholestasis in humans and rodents.
AB  - Organic solute transporter (OSTalpha-OSTbeta) is a novel heteromeric bile acid
      and sterol transporter expressed at the basolateral membranes of epithelium in
      the ileum, kidney, and liver. To determine whether OSTalpha-OSTbeta undergoes
      farnesoid X receptor (FXR)-dependent adaptive regulation following cholestatic
      liver injury, mRNA and protein expression levels were analyzed in patients with
      primary biliary cirrhosis (PBC) and following common bile duct ligation (CBDL) in
      rats and Fxr null and wild-type mice. Hepatic OSTalpha and OSTbeta mRNA increased
      3- and 32-fold, respectively, in patients with PBC compared with controls,
      whereas expression of Ostalpha and Ostbeta also increased in the liver of rats
      and mice following CBDL. In contrast, expression of Ostalpha and Ostbeta mRNA was
      generally lower in Fxr null mice, and CBDL failed to enhance expression of
      Ostalpha and Ostbeta compared with wild-type mice. HepG2 cells treated for 24 h
      with chenodeoxycholic acid, a selective FXR ligand, had higher levels of OSTalpha
      and OSTbeta mRNA and protein. Increases in OST protein were visualized by
      confocal microscopy at the plasma membrane. These results indicate that
      expression of Ostalpha and Ostbeta are highly regulated in response to
      cholestasis and that this response is dependent on the FXR bile acid receptor.

PMID- 16423921
TI  - Gene deletion of MK2 inhibits TNF-alpha and IL-6 and protects against cerulein
      induced pancreatitis.
AB  - Inflammatory effects contribute to the pathogenesis of pancreatitis. Clearly,
      proinflammatory cytokines like TNF-alpha and IL-6 are involved in this process
      and the associated systemic complications. The MAPKAPK-2 (MK2) signaling pathway
      is involved in cytokine gene expression. Therefore, we hypothesized that blockade
      of this pathway inhibits the expression of proinflammatory cytokines and thereby
      protects against pancreatitis. To investigate this, we used an in vivo mouse
      model with a homozygous deletion of the MK2 gene. Pancreatitis was induced by
      injection of cerulein. The severity was determined by measuring serum lipase,
      pancreatic trypsin activation, pancreatic edema, and morphological changes by
      quantitative scoring of histological sections. Systemic inflammation was
      evaluated by measuring myeloperoxidase activity in lung tissue. Serum levels of
      TNF-alpha and IL-6 were measured using an ELISA, and mRNA levels were identified
      using RT-PCR and subsequent quantitative PCR analysis. Pancreatitis in animals
      with deletion of the MK2 gene is less severe and accompanied with reduced serum
      levels of TNF-alpha and IL-6. Pancreatic mRNA levels revealed a fourfold
      reduction of IL-6 mRNA expression in MK2 -/- mice. Effects were associated with
      suppression of pancreatic trypsin activity and reduced acinar cell injury. In
      summary, these data show that gene deletion of MK2 ameliorates cerulein-induced
      pancreatitis. TNF-alpha and IL-6 signaling is mediated by the MK2 pathway and
      therefore crucial for the regulatory inflammatory processes. TNF-alpha expression
      is supposably regulated by a posttranscriptional mechanism, whereas IL-6
      expression is most likely regulated by transcriptional effects.

PMID- 16423923
TI  - cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells.
AB  - In guinea pig antral mucous cells, ACh stimulates the Ca(2+)-regulated
      exocytosis, which has a characteristics feature: an initial transient phase
      followed by a sustained phase. The effects of cGMP on ACh-stimulated exocytosis
      were studied in guinea pig antral mucous cells using video microscopy. cGMP
      enhanced the frequency of ACh-stimulated exocytotic events, whereas cGMP alone
      did not induce any exocytotic events under the ACh-unstimulated condition. cGMP
      did not stimulate either Ca(2+) mobilization or cAMP accumulation. The Ca(2+)
      dose-response studies demonstrated that cGMP shifted the dose-response curve
      upward with no shift to the lower concentration. This indicates that cGMP
      increased maximal responsiveness of the Ca(2+)-regulated exocytosis, but not the
      Ca(2+) sensitivity. Moreover, under a condition of ATP depletion by dinitrophenol
      (DNP) or anoxia (N(2) bubbling), ACh evoked only a sustained phase in exocytotic
      events with no initial transient phase. However, ACh evoked an initial transient
      phase followed by a sustained phase with addition of cGMP before ATP depletion,
      whereas only a sustained phase was evoked in a case of cGMP addition after ATP
      depletion. Thus cGMP-induced enhancement in ACh-stimulated exocytotic events
      requires ATP, suggesting that cGMP modulates ATP-dependent priming of Ca(2+)
      regulated exocytosis in antral mucous cells. In conclusion, cGMP increases the
      number of primed granules via acceleration of the ATP-dependent priming, which
      enhances the Ca(2+)-regulated exocytosis stimulated by ACh.

PMID- 16423922
TI  - Enteric glia inhibit intestinal epithelial cell proliferation partly through a
      TGF-beta1-dependent pathway.
AB  - Although recent studies have shown that enteric neurons control intestinal
      barrier function, the role of enteric glial cells (EGCs) in this control remains
      unknown. Therefore, our goal was to characterize the role of EGCs in the control
      of intestinal epithelial cell proliferation using an in vivo transgenic and an in
      vitro coculture model. Assessment of intestinal epithelial cell proliferation
      after ablation of EGCs in transgenic mice demonstrated a significant increase in
      crypt cell hyperplasia. Furthermore, mucosal glial network (assessed by
      immunohistochemical detection of S-100beta) is altered in colon adenocarcinoma
      compared with control tissue. In an in vitro coculture model of subconfluent Caco
      2 cells seeded onto Transwell filters with EGCs, Caco-2 cell density and
      [3H]thymidine incorporation were significantly lower than in control (Caco-2
      cultured alone). Flow cytometry analysis showed that EGCs had no effect on Caco-2
      cell viability. EGCs induced a significant increase in Caco-2 cell surface area
      without any sign of cellular hypertrophy. These effects by EGCs were also seen in
      various transformed or nontransformed intestinal epithelial cell lines.
      Furthermore, TGF-beta1 mRNA was expressed, and TGF-beta1 was secreted by EGCs.
      Exogenously added TGF-beta1 reproduced partly the EGC-mediated effects on cell
      density and surface area. In addition, EGC effects on Caco-2 cell density were
      significantly reduced by a neutralizing TGF-beta antibody. In conclusion, EGCs
      have profound antiproliferative effects on intestinal epithelial cells.
      Functional alterations in EGCs may therefore modify intestinal barrier functions
      and be involved in pathologies such as cancer or inflammatory bowel diseases.

PMID- 16423924
TI  - REMORA: a pilot in the ocean of BioMoby web-services.
AB  - Emerging web-services technology allows interoperability between multiple
      distributed architectures. Here, we present REMORA, a web server implemented
      according to the BioMoby web-service specifications, providing life science
      researchers with an easy-to-use workflow generator and launcher, a repository of
      predefined workflows and a survey system. CONTACT: Jerome.Gouzy@toulouse.inra.fr
      AVAILABILITY: The REMORA web server is freely available at
      http://bioinfo.genopole-toulouse.prd.fr/remora, sources are available upon
      request from the authors.

PMID- 16423925
TI  - SUSPECTS: enabling fast and effective prioritization of positional candidates.
AB  - SUSPECTS is a web-based server which combines annotation and sequence-based
      approaches to prioritize disease candidate genes in large regions of interest. It
      uses multiple lines of evidence to rank genes quickly and effectively while
      limiting the effect of annotation bias to significantly improve performance.
      AVAILABILITY: SUSPECTS is freely available at
      http://www.genetics.med.ed.ac.uk/suspects/ SUPPLEMENTARY INFORMATION: A quick
      start guide in Macromedia Flash format is available at
      http://www.genetics.med.ed.ac.uk/suspects/help.shtml and Excel spreadsheets
      detailing the comparative performance of the software are included as
      Supplementary material.

PMID- 16423926
TI  - Do we need more twin studies? The Healthy Twin Study, Korea.

PMID- 16423928
TI  - Comparison of computed and conventional whole lung tomography in detecting
      pulmonary nodules: a prospective radiologic-pathologic study. AJR 1978; 131:51
      54.

PMID- 16423929
TI  - Good things come in small packages: a review of the proceedings of the 2005
      Academy of Molecular Imaging Meeting.

PMID- 16423930
TI  - Report of a summit on molecular imaging.

PMID- 16423931
TI  - A liposomal nanoscale contrast agent for preclinical CT in mice.
AB  - OBJECTIVE: The goal of this study was to determine if an iodinated, liposomal
      contrast agent could be used for high-resolution, micro-CT of low-contrast, small
      size vessels in a murine model. MATERIALS AND METHODS: A second-generation,
      liposomal blood pool contrast agent encapsulating a high concentration of iodine
      (83-105 mg I/mL) was evaluated. A total of five mice weighing between 20 and 28 g
      were infused with equivalent volume doses (500 microL of contrast agent/25 g of
      mouse weight) and imaged with our micro-CT system for intervals of up to 240 min
      postinfusion. The animals were anesthetized, mechanically ventilated, and vital
      signs monitored allowing for simultaneous cardiac and respiratory gating of image
      acquisition. RESULTS: Initial enhancement of about 900 H in the aorta was
      obtained, which decreased to a plateau level of approximately 800 H after 2 hr.
      Excellent contrast discrimination was shown between the myocardium and cardiac
      blood pool (650-700 H). No significant nephrogram was identified, indicating the
      absence of renal clearance of the agent. CONCLUSION: The liposomal-based
      iodinated contrast agent shows long residence time in the blood pool, very high
      attenuation within submillimeter vessels, and no significant renal clearance
      rendering it an effective contrast agent for murine vascular imaging using a
      micro-CT scanner.

PMID- 16423933
TI  - Atypical polypoid adenomyoma of the uterus: appearance on (18)F-FDG PET/MRI fused
      images.

PMID- 16423932
TI  - Quantifying the effect of IV contrast media on integrated PET/CT: clinical
      evaluation.
AB  - OBJECTIVES: The use of IV contrast media in PET/CT can result in an
      overestimation of PET attenuation factors that potentially can affect
      interpretation. The objective of this study was to quantify the effect of IV
      contrast media in PET/CT and assess its impact on patients with intrathoracic
      malignancies. MATERIALS AND METHODS: Nine patients had CTs performed with and
      without IV contrast media followed by (18)F-FDG PET. PET images were
      reconstructed using contrast-enhanced and unenhanced CT. To quantify the effect
      of contrast media on standardized uptake values (SUV), similar regions of
      interest (ROIs) were drawn on the subclavian vein, heart, liver, spleen, and site
      of malignancy on both CT and corresponding reconstructed PET images, and the mean
      and maximum values were compared. In addition, two physicians blinded to the
      imaging parameters that were used evaluated the reconstructed PET images to
      assess whether IV contrast media had an effect on clinical interpretation.
      RESULTS: For all patient studies, the subclavian vein region on the ipsilateral
      side of contrast media administration had the highest increase in CT numbers with
      a corresponding average SUV(max) increase of 27.1%. Similarly, ROIs of the heart
      and at the site of malignancy showed an increase in the maximum attenuation value
      with a corresponding average SUV(max) increase of 16.7% and 8.4%, respectively.
      Other locations had relatively small attenuation value differences with a
      correspondingly negligible SUV variation. CONCLUSION: Although there is a
      significant increase in SUV in regions of high-contrast concentration when
      contrast-enhanced CT is used for attenuation correction, this increase is
      clinically insignificant. Accordingly, in PET/CT, IV contrast-enhanced CT can be
      used in combination with the PET to evaluate patients with cancer.

PMID- 16423935
TI  - When, why, and how to examine the heart during thoracic CT: Part 2, clinical
      applications.
AB  - OBJECTIVE: CT examination of the thorax is often requested for the investigation
      of disorders that may have an important underlying cardiac cause or association
      that is not clinically obvious. Conditions such as idiopathic and acquired
      cardiomyopathy, ischemic heart disease, and valvular dysfunction may underlie
      symptoms such as dyspnea, chest pain, and hemoptysis that prompt the request for
      CT of the thorax. Other conditions such as pulmonary thromboembolic disease,
      chronic obstructive airways disease, pectus excavatum, sleep apnea, and many
      intrathoracic malignancies may have an important effect on cardiac structure and
      function. Patients undergoing thoracic surgery may have unsuspected coronary
      artery disease that can be detected in the course of preoperative evaluation by
      CT; similarly, postoperative complications often have a cardiogenic basis.
      CONCLUSION: Examination of the heart in the course of CT of the chest often can
      provide important and clinically relevant information that is not otherwise
      easily available.

PMID- 16423934
TI  - When, why, and how to examine the heart during thoracic CT: Part 1, basic
      principles.
AB  - OBJECTIVE: MDCT systems with fast scanning capabilities can acquire images of the
      thorax with reduced cardiac motion artifacts, enabling improved evaluation of the
      heart and surrounding structures in the course of routine thoracic CT. This
      article describes the principles of including an evaluation of the heart in the
      course of a chest CT examination in terms of both examination technique and image
      interpretation. In addition, both the normal appearances and some of the most
      common abnormal appearances of the cardiac structures will be described.
      CONCLUSION: Details concerning the cardiac structures can inform interpretation
      of thoracic CT studies and can influence the patient's clinical management. Both
      unenhanced and contrast-enhanced scans can detect significant cardiac disorders
      that may otherwise go undetected. In certain situations, a CT examination of the
      entire chest, complemented by cardiac gating, can provide a more dedicated
      analysis of the heart and coronary arteries, providing both morphologic and
      functional information.

PMID- 16423936
TI  - Aortic valve calcification as an incidental finding at CT of the elderly:
      severity and location as predictors of aortic stenosis.
AB  - OBJECTIVE: The purpose of this study was to correlate the severity and location
      of aortic valve calcifications, as an incidental finding at chest CT of elderly
      persons, with pressure gradients across the valve. MATERIALS AND METHODS: One
      hundred fifteen subjects who were 60 years old or older and who showed aortic
      valve calcification on chest CT (5-mm reconstructed section width, no IV contrast
      material) and who had also undergone transthoracic echocardiography within 3
      months of the CT examination were identified retrospectively. Aortic valve
      calcification scores (Agatston and volumetric) and subjective calcification
      pattern scores (based on a 9-point scale) were calculated and correlated with
      echocardiographic gradients. RESULTS: Thirty patients (26%) (median age, 81
      years) were identified who showed an increased pressure gradient across the
      aortic valve at echocardiography. Eighty-five subjects (74%), including 30 age
      matched but otherwise randomly selected control subjects, showed no increase in
      pressure gradient. The severity of aortic valve calcification was greater for the
      30 subjects with an increased gradient than for the control subjects (p <
      0.0001). Increased mean and peak gradients across the aortic valve correlated
      with the subjective scores for aortic valve calcification (r = 0.69 and 0.65,
      respectively; p < 0.0001), with Agatston scores (r = 0.76 and 0.70, respectively;
      p < 0.0001), and with volumetric scores (r = 0.78 and 0.73, respectively; p <
      0.0001). In terms of specific commissures, the greatest correlation with mean and
      peak gradients was for peripheral left-posterior commissural calcification (r =
      0.71 and 0.65, respectively; p < 0.0001) and central right-left commissural
      calcification (r = 0.69 and 0.66, respectively; p < 0.0001). CONCLUSION: The
      severity of aortic valve calcifications on chest CT, as assessed either
      subjectively or objectively, correlated with increased pressure gradients across
      the aortic valve, particularly for calcification of the peripheral left-posterior
      commissure and the central right-left commissure. These results indicate that the
      severity and location of aortic valve calcifications on chest CT are associated
      with an increased pressure gradient across the aortic valve.

PMID- 16423937
TI  - MDCT evaluation of aortic valvular disease.
AB  - OBJECTIVE: This essay depicts recent advances of MDCT in the evaluation of aortic
      valvular disease. CONCLUSION: Aortic valvular disease can be assessed with
      current MDCT technology. The improved imaging characteristics of MDCT have
      significantly decreased artifacts traditionally seen with prosthetic aortic
      valves and enabled excellent visualization of valve function. Advances in ECG
      gated MDCT technology offer the opportunity to evaluate a variety of aortic
      valvular abnormalities.

PMID- 16423938
TI  - Percutaneous left atrial appendage transcatheter occlusion (PLAATO): planning and
      follow-up using contrast-enhanced MRI.

PMID- 16423939
TI  - Myxoid fibrosarcoma of a pulmonary vein with extension into the left atrium.

PMID- 16423940
TI  - Drug-induced eosinophilic pneumonia: high-resolution CT findings in 14 patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the high-resolution CT
      findings of drug-induced eosinophilic pneumonias. CONCLUSION: Drug-induced
      eosinophilic pneumonias usually manifest as areas of consolidation and ground
      glass opacity most commonly involving the outer third of the lungs.

PMID- 16423941
TI  - 16-MDCT aortography with a low-dose contrast material protocol.
AB  - OBJECTIVE: The objective of our study was to evaluate whether a low-dose contrast
      material (CM) protocol with a saline flush might provide sufficient contrast
      enhancement in aortoiliac 16-MDCT angiography. SUBJECTS AND METHODS: Forty-five
      patients were divided into two groups on the basis of the CM (300 mg I/mL)
      administration protocol: group 1 (23 patients) received 100 mL of CM at 3.0
      mL/sec; and group 2 (22 patients), 50 mL of CM at 3.0 mL/sec followed by a 20-mL
      saline flush at 3.0 mL/sec. All patients underwent 16-MDCT angiography of the
      entire aortoiliac region. Seven regions of interest (ROIs) were drawn from the
      ascending aorta (ROI 1) to the external iliac artery (ROI 7). Quantitative
      analysis was performed by calculating the mean aortoiliac attenuation and the
      mean difference between the maximum and minimum attenuation values. Vascular
      enhancement of the renal arteries was visually assessed using 2D and 3D
      postprocessing techniques. RESULTS: The mean aortoiliac attenuation in group 1
      was 314.3 +/- 45.9 H and that in group 2 was 306.1 +/- 35.0 H. The difference was
      not statistically significant. Adequate mean aortoiliac attenuation was achieved
      in 95.7% (22/23) and 95.5% (21/22) of patients in groups 1 and 2, respectively.
      The difference was not statistically significant. The mean difference between the
      maximum and minimum attenuation values was significantly smaller in group 1 (41.3
      +/- 16.8 H) than in group 2 (57.2 +/- 25.3 H). The renal arteries were assessable
      in all patients in both groups. CONCLUSION: This protocol of 50 mL of CM with a
      saline flush provides attenuation comparable to that obtained with the 100 mL of
      CM in aortoiliac 16-MDCT angiography.

PMID- 16423942
TI  - Simulation of aortic peak enhancement on MDCT using a contrast material flow
      phantom: feasibility study.
AB  - OBJECTIVE: The objective of our study was to develop a flow phantom simulating
      aortic peak enhancement after the injection of contrast material on CT and to
      investigate the validity of the flow phantom by comparing the time-enhancement
      curves obtained for the flow phantom and humans. MATERIALS AND METHODS: We
      developed a flow phantom simulating the enhancement pattern of the aorta after
      the injection of contrast material. In protocols 1, 2, and 3 of the phantom
      study, 90, 102, and 150 mL of iohexol, respectively, was administered over 35
      sec. In protocol 4, 102 mL of iohexol was administered over 25 sec. In phantom
      protocols 1', 2', and 3', the dose and contrast injection duration were the same
      as in protocols 1, 2, and 3; however, saline (10 mL) was injected during the 20
      sec after contrast delivery. In the human study, 20 patients were randomized into
      four groups: Groups A, B, and C received 1.5, 1.7, and 2.5 mL of iohexol per
      kilogram of body weight, respectively, over 35 sec; and group D received 1.7
      mL/kg over 25 sec. In patient groups A, B, C, and D, phantom protocols 1, 2, 3,
      and 4 were used, respectively. Single-level serial CT scans were obtained using a
      16-MDCT scanner on the simulated and real aortas after the injection of contrast
      material. Time-enhancement curves of simulated and real aortas were generated,
      and aortic peak times and aortic peak enhancement values were calculated.
      RESULTS: Aortic peak enhancement and aortic peak times in protocols 1-4 and 1'-3'
      of the phantom study were 2-8% larger and 6-18% longer, respectively, than in the
      corresponding patient study. The shape of the time-enhancement curves before
      aortic peak time in protocols 1-3 and 1'-3' of the phantom study closely
      resembled that of the corresponding patient study. After the aortic peak time,
      the shape of time-enhancement curves in protocols 1, 2, and 3 of the phantom
      study was different from the corresponding patient study; however, it was similar
      in phantom protocols 1'-3' and the corresponding patient study. In all four
      phantom protocols, the difference between maximal and minimal aortic peak
      enhancement was less than the SD of the corresponding patient study. CONCLUSION:
      The level of peak aortic enhancement and the time to peak aortic enhancement were
      similar in the phantom and human studies when we used our different contrast
      injection protocols for MDCT.

PMID- 16423943
TI  - MR angiography for abdominal and thoracic aortic aneurysms: assessment before
      endovascular repair in patients with impaired renal function.
AB  - OBJECTIVE: The aim of the study was to establish the feasibility of using MR
      angiography as the sole imaging technique before endovascular repair of abdominal
      or thoracic aortic aneurysms and to compare preprocedural measurements by MR
      angiography and digital subtraction angiography in patients with impaired renal
      function. CONCLUSION: MR angiography appears to be effective and reliable for use
      as the sole imaging method before endovascular repair of aortic aneurysms in
      patients with renal impairment.

PMID- 16423944
TI  - Innominate artery occlusive disease: sonographic findings.
AB  - OBJECTIVE: The objective of this study was to report the sonographic
      abnormalities in a group of patients with angiographically proven innominate
      artery stenosis and occlusion. MATERIALS AND METHODS: A review of all
      cerebrovascular sonograms at our institutions was undertaken to identify patients
      with complete or partial flow reversal in the right vertebral artery and reversal
      or midsystolic deceleration of flow in any one of the three major segments of the
      right carotid system (common, internal, or external carotid artery). The
      distribution and appearance of these abnormalities was evaluated, and the
      presence or absence of tardus-parvus waveforms was noted in any segment of the
      right carotid artery. Additionally, a left to right common carotid peak systolic
      velocity ratio (LCCA/RCCA) was calculated and compared to published normal
      values. All patients had correlative contrast or MR angiography. Correlation was
      made between the severity of stenosis as determined by angiographic images and
      waveform aberrations as well as the more objective LCCA/RCCA ratios. RESULTS:
      Twelve patients were identified as having the abnormalities described above in
      the right vertebral and carotid arteries. Doppler waveforms from the right
      vertebral artery revealed that eight of the 12 patients had complete reversal of
      flow at rest. Bidirectional flow was found in the remaining four as manifested by
      the presence of marked midsystolic deceleration. In the carotid arteries, one
      patient had complete reversal of flow in all segments of the right carotid
      system. Waveforms with midsystolic deceleration were identified in at least one
      of the carotid arteries of the remaining 11 patients: common carotid artery (8/11
      = 73%), internal carotid artery (10/11 = 91%), external carotid artery (3/11 =
      27%). The average LCCA/RCCA was 3.1 with a range of 1.7 to 5.7 (normal = 0.7
      1.3). All patients had severe innominate artery disease (from 70% to occlusion)
      by contrast angiography or MR angiography. There was no correlation between the
      angiographically determined degree of stenosis and the Doppler findings.
      CONCLUSION: A distinctive pattern of hemodynamic alterations occurs in the right
      vertebral and carotid arteries of patients with severe innominate artery disease.
      Findings include reversed or bidirectional flow in the right vertebral artery,
      the presence of midsystolic deceleration in any of the branches of the right
      carotid system, and elevated LCCA/RCCA ratio.

PMID- 16423945
TI  - Development of nonobstructive intraarterial thrombi after injection of thrombin
      into pseudoaneurysms.
AB  - OBJECTIVE: Our objective was to describe the development of nonobstructive,
      localized intraarterial thrombi after percutaneous injection of thrombin into
      femoral pseudoaneurysms. CONCLUSION: Partial extension of thrombi into the
      arterial lumen may occur after injection of thrombin into small pseudoaneurysms
      with short necks. In our experience, this is an asymptomatic and self-limited
      complication of the procedure.

PMID- 16423946
TI  - IV contrast selection for MDCT: current thoughts and practice.
AB  - OBJECTIVE: The purpose of this article is to review studies evaluating how
      contrast concentration affects MDCT of the body and to report IV contrast
      infusion protocols from MDCT angiography and MDCT of abdominal tumors.
      CONCLUSION: Higher concentrations (350 mg I/mL or greater) may improve
      visualization of small abdominal arteries. However, preliminary data comparing
      300 mg I/mL to higher concentrations for MDCT of hypervascular hepatocellular
      carcinoma and pancreatic cancer have shown that higher concentrations may not
      increase tumor conspicuity.

PMID- 16423947
TI  - Digital volume tomography: radiologic examinations of the temporal bone.
AB  - OBJECTIVE: We evaluated the clinical applicability and the value of digital
      volume tomography for visualization of the lateral skull base using temporal bone
      specimens. MATERIALS AND METHODS: Twelve temporal bone specimens were used to
      evaluate digital volume tomography on the lateral skull base. Aside from the
      initial examination of the temporal bones, radiologic control examinations were
      performed after insertion of titanium, gold, and platinum middle-ear implants and
      a cochlear implant. RESULTS: With high-resolution and almost artifact-free
      visualization of alloplastic middle-ear implants of titanium, gold, or platinum,
      it was possible to define the smallest bone structures or position of the
      prosthesis with high precision. Furthermore, the examination proved that digital
      volume tomography is useful in assessing the normal position of a cochlear
      implant. CONCLUSION: Digital volume tomography expands the application of
      diagnostic possibilities in the lateral skull base. Therefore, we believe
      improved preoperative diagnosis can be achieved along with more accurate planning
      of the surgical procedure. Digital volume tomography delivers a small radiation
      dose and a high resolution coupled with a low purchase price for the equipment.

PMID- 16423948
TI  - Does size matter? Positive predictive value of MRI-detected breast lesions as a
      function of lesion size.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of lesion size
      on the positive predictive value (PPV) of biopsy in MRI-detected breast lesions.
      MATERIALS AND METHODS: A retrospective review was performed of 666 consecutive
      nonpalpable, mammographically occult lesions that had MRI-guided localization.
      MRI examinations were performed using a 1.5-T magnet. Lesions were measured by
      the interpreting radiologist before biopsy. Malignancy rate versus lesion size
      was determined. RESULTS: The median MRI lesion size was 1 cm (range, 0.3-7.0 cm).
      Malignancy was present in 149/666 (22%) lesions, of which 80 (54%) were ductal
      carcinoma in situ (DCIS), 66 (44%) were invasive cancer, and three (2%) were
      lymphoma. The frequency of malignancy increased significantly (p = 0.0005) with
      lesion size, with malignancy found in one (3%) of 37 lesions less than 5 mm, 44
      (17%) of 254 lesions 5-9 mm, 37 (25%) of 151 lesions 10-14 mm, 21 (28%) of 74
      lesions 15-19 mm, and 46 (31%) of 150 lesions 20 mm or larger. Lesions less than
      5 mm accounted for 37 (6%) of 666 lesions that had a biopsy and one (< 1%) of 149
      cancers (one DCIS). Among lesions less than 10 mm, the likelihood of malignancy
      was highest in postmenopausal women (22% malignant) and in the extent of disease
      setting (22% malignant), and lowest in premenopausal women (10% malignant) and in
      the high-risk screening setting (10% malignant). CONCLUSION: The PPV of biopsy
      for lesions identified at breast MRI using a 1.5-T magnet significantly increased
      with increasing lesion size. Biopsy is rarely necessary for lesions smaller than
      5 mm because of their low (3%) likelihood of cancer. Further work is needed to
      develop an algorithm that uses size in addition to other patient and lesion
      factors to guide biopsy recommendations for MRI-detected breast lesions.

PMID- 16423949
TI  - Breast-conserving surgery after chemotherapy: value of MDCT for determining tumor
      distribution and shrinkage pattern.
AB  - OBJECTIVE: For this study, we investigated the usefulness of MDCT in assessing
      the extent of residual breast cancer after neoadjuvant chemotherapy. To ensure
      the success of breast-conserving surgery, we evaluated the usefulness of
      determining the tumor distribution before neoadjuvant chemotherapy and the
      shrinkage pattern after neoadjuvant chemotherapy. SUBJECTS AND METHODS: MDCT
      before and after neoadjuvant chemotherapy was performed in 46 consecutive
      patients with 47 locally advanced breast cancers. The distribution pattern of
      contrast enhancement on MDCT before neoadjuvant chemotherapy was classified into
      five categories: solitary lesion, grouped lesion (localized lesion with linear,
      spotty, or linear and spotty enhancement), separated lesion (multiple foci of
      contrast enhancement), mixed lesion (grouped lesion with multiple foci), and
      replaced lesion (diffuse contrast enhancement in whole quadrants). RESULTS: There
      was agreement between the MDCT assessment and pathologic findings in 44 (94%) of
      the 47 tumors. In the partial response group with nonreplaced lesions, MDCT
      revealed three shrinkage patterns: pattern 1a, concentric shrinkage without
      surrounding lesions; pattern 1b, concentric shrinkage with surrounding lesions;
      and pattern 2, shrinkage with residual multinodular lesions. Breast-conserving
      surgery was performed successfully in 14 patients including complete response
      cases that were detected on the basis of MDCT findings and partial response cases
      that were detected on the basis of observation of pattern 1 shrinkage. In all
      five patients with pattern 2 shrinkage, CT underestimated the residual tumor
      extent by more than 2 cm. CONCLUSION: MDCT classification of tumor distribution
      before neoadjuvant chemotherapy and of shrinkage patterns after neoadjuvant
      chemotherapy is important in the preoperative evaluation of patients undergoing
      breast-conserving surgery.

PMID- 16423950
TI  - MDCT of the gonadal veins in females with large pelvic masses: value in
      differentiating ovarian versus uterine origin.
AB  - OBJECTIVE: The objective of our study was to determine the usefulness of
      recognizing the continuity of the gonadal veins to the pelvic mass to
      differentiate ovarian versus uterine origin on MDCT in females with a large
      pelvic mass. MATERIALS AND METHODS: Two radiologists interpreted the MDCT images
      obtained on a monitor, using paging methods, in 86 female patients with a large
      pelvic mass (> 8 cm) and 40 patients without an abdominopelvic mass as control
      subjects. The following issues were recorded using a 5-point scale: visualization
      of gonadal veins and origin determination based on anatomic continuity. Receiver
      operating characteristic (ROC) curve analysis was performed, and the
      interobserver differences were checked with kappa statistics. The maximum
      diameters of the gonadal veins were also measured. With consensus
      interpretations, the sensitivity, specificity, and accuracy of ovarian origin
      determination were calculated. RESULTS: Gonadal veins were shown in more than 70%
      of the subjects in both the control group and the patients with a mass (hereafter
      referred to as the "mass group"). There was no significant difference in the
      diameter of the gonadal veins between the control and mass groups and between
      patients with an ovarian mass and those with a uterine mass. The values for the
      area under the ROC curve (A(z)) of the two observers for ovarian origin
      determination were 0.90 and 0.92. The kappa value was 0.48. The sensitivity,
      specificity, and accuracy were 83.3%, 87.5%, and 84.9%, respectively. CONCLUSION:
      Gonadal veins can be shown on MDCT with high consistency; MDCT provides useful
      information for determining the origin of relatively large pelvic tumors arising
      in females.

PMID- 16423951
TI  - Sensitivity of MR arthrography in the evaluation of acetabular labral tears.
AB  - OBJECTIVE: MRI has historically provided suboptimal visualization of tears of the
      acetabular labrum. Degenerative fraying and underlying cartilage abnormalities
      can often mimic tears of the labrum on conventional MRI. Administration of
      intraarticular gadolinium enhances the MRI appearance of the labrum to improve
      detection of labral abnormalities. This study examined the improved diagnostic
      sensitivity of MR arthrography compared with conventional MRI and the importance
      of confining the study to a small field of view. MATERIALS AND METHODS: Fifty-one
      hips were imaged in 48 patients. Fourteen hips underwent conventional MRI with a
      large field of view (30-38 cm). Seven hips underwent conventional MRI with a
      small field of view (14-20 cm). Thirty hips underwent MR arthrography with a
      small field of view (14-20 cm). Labral tears were diagnosed when contrast
      material was identified within the labrum or between the labrum and the
      acetabulum, when a displaced fragment was noted, or when a paralabral cyst was
      identified. All study results were compared with findings at the time of hip
      arthroscopy. RESULTS: Conventional MRI with a large field of view was 8%
      sensitive in detecting labral tears compared with findings at the time of
      arthroscopy. Diagnostic sensitivity was improved to 25% with a small field of
      view. MR arthrography with a small field of view was 92% sensitive in detecting
      labral tears. CONCLUSION: A combination of MR arthrography and a small field of
      view is more sensitive in detecting labral abnormalities than is conventional MRI
      with either a large or a small field of view.

PMID- 16423952
TI  - Abnormalities on MRI of the subscapularis tendon in the presence of a full
      thickness supraspinatus tendon tear.
AB  - OBJECTIVE: Our objective was to determine the association between size and
      chronicity of full-thickness supraspinatus tendon tears with subscapularis tendon
      abnormalities on MRI. MATERIALS AND METHODS: One hundred forty-two MRI
      examinations with full-thickness supraspinatus tendon tears were categorized on
      the basis of the supraspinatus muscle (SS): normal muscle (SS(normal)),
      suggesting a recent or small tear; reduced muscle bulk without fatty atrophy
      (SS(volume loss)); and those with fatty atrophy, suggesting a large or chronic
      tear (SS(fatty atrophy)). Subscapularis tendon abnormalities, the subcoracoid
      interval, and subcortical bone marrow edema in the lesser tuberosity and coracoid
      process were recorded. RESULTS: The mean size of supraspinatus tendon tears in
      the SS(normal) (n = 45) group was 8.5 mm, 16.6 mm in SS(volume loss) (n = 53),
      and 29 mm in the SS(fatty atrophy) group (n = 44). Subscapularis tendon
      abnormality was identified in 22% of SS(normal) patients, 61% of SS(volume loss),
      and 86% of the SS(fatty atrophy) group (p < 0.001). There was moderate
      correlation between chronicity of supraspinatus tendon tears and subscapularis
      tendon abnormality (r = 0.47; p < 0.0001), with no correlation between the
      subcoracoid interval and abnormalities of the subscapularis tendon. There was
      moderate correlation between chronicity of supraspinatus tendon tears and bone
      marrow changes in the lesser tuberosity (r = 0.44; p < 0.0001). CONCLUSION:
      Subscapularis tendon abnormality is related to chronicity of supraspinatus tendon
      tears. Bone marrow edema in the lesser tuberosity with a subscapularis tendon
      abnormality suggests increased stress at the subscapularis tendon insertion with
      chronicity of full-thickness supraspinatus tendon tears. Lack of correlation with
      the subcoracoid interval indicates that anterior instability may be a more
      important contributing factor to subscapularis tendon abnormalities than static
      subcoracoid impingement in the setting of a full-thickness supraspinatus tendon
      tear.

PMID- 16423953
TI  - MRI of the popliteomeniscal fasciculi.
AB  - OBJECTIVE: The purpose of this study was to further our understanding of the
      normal appearance of the popliteomeniscal fasciculi (PMF) on MRI after the
      determination of finely tuned imaging parameters. For this purpose we performed
      the study in two stages. Stage I was to determine suitable parameters for
      depicting the popliteomeniscal fasciculi. Stage II was to classify the "normal"
      image. CONCLUSION: The findings presented in this article will contribute to the
      understanding of the normal appearance of the popliteomeniscal fasciculi on MRI,
      and of the degree of variation of this structure among the population.

PMID- 16423954
TI  - Radiologic-pathologic conferences of the University of Texas M. D. Anderson
      Cancer Center: Chondromyxoid fibroma of the sacrum and left iliac bone.

PMID- 16423955
TI  - MRI of knee osteonecrosis in children with leukemia and lymphoma: Part 1,
      observer agreement.
AB  - OBJECTIVE: The aim of this study was to determine whether a new MRI-based staging
      system for osteonecrosis of the knee in pediatric patients could be used with an
      acceptable level of intra- and interobserver agreement. MATERIALS AND METHODS: We
      conducted a retrospective analysis of MRI studies of the knee performed in a
      single institution between April 1994 and July 2003. Knee osteonecrosis was
      identified in 168 children with a primary diagnosis of hematologic malignancy.
      This substantial number prompted us to design a staging system for use with
      pediatric patients. To assess interobserver reliability of two primary observers
      in using the system, they reviewed and interpreted the same 36 imaging studies of
      randomly chosen patients. For the assessment of intraobserver reproducibility,
      each observer rereviewed 16 studies. A senior observer coded potential causes of
      disagreement between the primary observers. RESULTS: Interobserver agreement was
      substantial: the kappa value was 0.66 (95% confidence interval [CI], 0.58-0.75)
      in locations where the observers had to record only the presence or absence of a
      lesion, and the weighted kappa value was 0.65 (95% CI, 0.59-0.72) in locations
      where they had to classify the extent of involvement. The presence of marrow
      edema, punctate foci of altered signal, and mottled marrow changes was associated
      with a higher level of disagreement between the primary observers. CONCLUSION:
      Our proposed classification system, developed specifically for use with MRI, was
      used with substantial intra- and interobserver agreement. We think its use can
      contribute to a standardized approach to the interpretation of MRI findings in
      pediatric osteonecrosis of the knee.

PMID- 16423956
TI  - MRI of knee osteonecrosis in children with leukemia and lymphoma: Part 2,
      clinical and imaging patterns.
AB  - OBJECTIVE: This aim of this study was to explore the relationship between MRI
      findings and clinical symptoms of knee osteonecrosis in children and to determine
      the significance of this relationship. Such information is important for early
      diagnosis of this frequent complication and for choosing an appropriate treatment
      strategy. MATERIALS AND METHODS: Osteonecrotic lesion size and location were
      determined in a retrospective analysis of MR images of the knee obtained in our
      institution during the past 10 years. Association between MRI findings and
      clinical symptoms expressed by the knee scores was tested for a subgroup of our
      patient population who had clinical evaluation of the knees in the orthopedic
      clinic within 6 weeks of their MRI studies. RESULTS: In 80% of patients,
      osteonecrosis was bilateral. Lesions were distributed as follows: femur and
      tibia, 66% of the knees; femur alone, 26%; and tibia alone, 8%. Clinical symptoms
      of knee osteonecrosis were associated with lesions involving the articular
      surface of the distal femur, large lesions, and involvement of any part of the
      tibia. MR images showed milder osteonecrosis in patients who were less than 10
      years old at the time of primary diagnosis. CONCLUSION: Osteonecrosis affecting
      the knees of children treated for leukemia and lymphoma is mostly asymptomatic.
      Children who are 10 years old or older have signs of more advanced osteonecrosis.
      Clinical symptoms often lag MRI presentation and may develop late in the course
      of the disease. Routine MRI evaluation is recommended for timely diagnosis of
      treatment-induced osteonecrosis.

PMID- 16423957
TI  - Solid extratesticular masses in children: radiographic and pathologic
      correlation.
AB  - OBJECTIVE: The purpose of this pictorial essay is to review the sonographic and
      pathologic appearances of the most common solid and complex extratesticular
      masses in children. CONCLUSION: Solid or complex extratesticular masses,
      especially those that are rapidly growing and are painless, raise concerns
      regarding malignant rhabdomyosarcoma. Mimickers of rhabdomyosarcoma include
      inflammatory processes such as pseudotumor, chronic epididymitis, or meconium
      periorchitis. Because sonography cannot distinguish benign from malignant,
      worrisome extratesticular masses should be biopsied or removed.

PMID- 16423958
TI  - Clinical significance of poor CT enhancement of the thickened small-bowel wall in
      patients with acute abdominal pain.
AB  - OBJECTIVE: Our purpose was to compare clinical outcomes in patients with acute
      abdominal pain and inner-layer enhancement of a thickened small-bowel wall, as
      shown on CT, with outcomes in similar patients without such enhancement.
      MATERIALS AND METHODS: We retrospectively studied outcomes in 126 patients with
      acute abdominal pain and small-bowel wall thickening on CT: 84 with inner-layer
      enhancement and 42 without this enhancement. We compared the surgical, small
      bowel resection, small-bowel necrosis, and mortality rates between the two groups
      using the chi-square test. RESULTS: Among the 42 patients without inner-layer
      enhancement, 32 (76%) underwent an operation, 27 (64%) received segmental small
      bowel resection, 26 (62%) had small-bowel necrosis, and seven (17%) died. All of
      these proportions were significantly higher (p < 0.01) than the corresponding
      rates-34 (40%), nine (11%), five (6%), and two (2%), respectively-in the 84
      patients with inner-layer enhancement. All 31 patients with necrotic small bowel
      had pathologic evidence of ischemic necrosis involving the mucosa. CONCLUSION:
      Among patients with acute abdominal pain, those whose CT scans did not show inner
      layer enhancement of a thickened small-bowel wall were more prone to undergo
      surgery and small-bowel resection and were more likely to have small-bowel
      necrosis than those with such enhancement. Poor inner-layer enhancement on CT
      might be consistent with sloughed or necrotic mucosa, as observed on pathology.

PMID- 16423959
TI  - Diagnosis of duct disruption and assessment of pancreatic leak with dynamic
      secretin-stimulated MR cholangiopancreatography.
AB  - OBJECTIVE: The management of pancreatic duct disruption is complex and depends on
      several factors including the cause, morphology, and degree of disruption. ERCP
      can show duct disruption in as many as 75% of patients but is invasive and cannot
      detect disruption beyond an obstruction. We studied the role of secretin MR
      cholangiopancreatography in patients with suspected pancreatic duct disruption.
      CONCLUSION: Secretin MR cholangiopancreatography is a safe, noninvasive test that
      can provide additional useful information about duct integrity and facilitate
      management.

PMID- 16423960
TI  - Diffuse mesenteric extramedullary hematopoiesis with ascites: sonography, CT, and
      MRI findings.

PMID- 16423961
TI  - MDCT appearance of gastrointestinal stromal tumors after therapy with imatinib
      mesylate.
AB  - OBJECTIVE: Our objective was to determine the MDCT appearance of gastrointestinal
      stromal tumors (GISTs) after treatment with imatinib mesylate. CONCLUSION: Cystic
      changes within primary and metastatic GISTs seen on MDCT in patients after
      imatinib mesylate therapy are evidence of disease response. Calcification may
      also occur in lesions that respond to therapy.

PMID- 16423962
TI  - 3.0- Versus 1.5-T MR cholangiography: a pilot study.
AB  - OBJECTIVE: The purpose of our study was to evaluate quantitative and qualitative
      image quality of MR cholangiography at a field strength of 3.0 T compared with
      the standard field strength of 1.5 T. MATERIALS AND METHODS: A standardized MR
      cholangiography sequence protocol was used for 15 healthy male volunteers (mean
      age +/- SD, 32.4 +/- 4.3 years) who underwent both 1.5- and 3.0-T MRI within 2 hr
      in an alternating fashion. Dedicated circular polarized torso coils (1.5 and 3.0
      T) were used. The sequence protocol included breath-hold single-slice rapid
      acquisition with relaxation enhancement (slice thickness, 50 mm; orientation,
      coronal and +/- 20 degrees oblique coronal); breath-hold multislice HASTE (slice
      thickness, 3 mm; coronal only); and a non-breath-hold, respiratory-triggered 3D
      turbo spin-echo (TSE) T2-weighted sequence (slice thickness, 1 mm; 60 slices per
      slab; coronal only). Maximum intensity projections were generated from each
      multislice data set. Bile duct (common bile duct, right posterior segmental
      branch, and left hepatic duct) to periductal tissue contrast-to-noise ratios were
      compared at 1.5 and 3.0 T. Qualitative image analysis was performed by three
      independent reviewers. Qualitative analysis included delineation of the extra-
      and intrahepatic biliary anatomy, with specific attention given to the presence
      (or absence) of cystic or intrahepatic ductal variants, using a 4-point
      confidence scale. Statistical analysis consisted of the paired Student's t test
      and the signed rank test. RESULTS: Contrast-to-noise ratios between the bile duct
      and the periductal tissue were higher at 3.0 T in all three locations (common
      bile duct, right posterior segmental branch, and left hepatic duct). In each
      magnet class, the 3D TSE sequence offered the best contrast-to-noise ratio and
      qualitative analysis. Superiority of the 3D TSE sequence was statistically
      significant in all analyses. Five of the 15 volunteers had intrahepatic biliary
      variants that were detected with a higher level of confidence (p < 0.01) on the
      3.0-T system than on the 1.5-T system. CONCLUSION: Compared with MR
      cholangiography at 1.5 T, MR cholangiography at 3.0 T offers improved contrast-to
      noise ratio and a higher level of confidence for depicting intrahepatic variants.

PMID- 16423963
TI  - Complications of adjustable gastric banding, a radiological pictorial review.
AB  - OBJECTIVE: The purpose of this article is to review the radiologic appearance of
      complications of the adjustable gastric band. CONCLUSION: Continuous progress in
      surgical technique of adjustable gastric banding and the increasing experience of
      surgeons have decreased the rate of complications. However, because different
      complications may have the same clinical presentation but require different
      treatment, to give a definitive diagnosis, the radiologist must be aware of the
      surgical procedures and possible sequelae.

PMID- 16423964
TI  - Inverted appendiceal stumps simulating large pedunculated polyps on screening CT
      colonography.

PMID- 16423965
TI  - Retained seminal vesicles after radical prostatectomy: frequency, MRI
      characteristics, and clinical relevance.
AB  - OBJECTIVE: Changes after radical prostatectomy (RP) may present potential
      pitfalls in the interpretation of pelvic MRI studies in post-RP patients. One
      such change is retained seminal vesicles (SVs). The purpose of this study was to
      characterize the MRI features and evaluate the frequency of retained SV remnants
      in patients after RP. CONCLUSION: Retained SV remnants are a common finding after
      RP. Most are fibrotic distal tips. Recognition of SV remnants may prevent their
      misinterpretation as local recurrences.

PMID- 16423967
TI  - Visualization and quantification of flow and velocity fields in intracranial
      arteriovenous malformations using phase-contrast MR angiography.
AB  - OBJECTIVE: The objective of this study was to describe postprocessing tools for
      MR phase-contrast flow quantification images and apply those tools to cerebral
      arteriovenous malformations (AVMs) to visualize blood flow dynamics
      noninvasively. CONCLUSION: Inflow and outflow zones were clearly depicted at
      different regions in the AVM. The processed images showed flow patterns including
      vortical flow and variations in velocity over the cardiac cycle. Particle
      tracking gave an impression of the overall flow state and of the venous drainage
      system in particular.

PMID- 16423968
TI  - Postbiopsy arterioportal fistula in patients with hepatocellular carcinoma:
      clinical significance in transarterial chemoembolization.
AB  - OBJECTIVE: The purpose of this study was to determine, retrospectively, the
      frequency of postbiopsy arterioportal fistula in hepatocellular carcinoma and its
      significance in transarterial chemoembolization (TACE). MATERIALS AND METHODS:
      Forty-one patients who underwent percutaneous liver biopsy for diagnosis of
      hepatocellular carcinoma were referred for TACE. The control population comprised
      161 patients referred during the same period who underwent TACE without biopsy.
      We determined that an arterioportal fistula was present by opacification of the
      portal vein during the arterial phase of angiography or by opacification with
      iodized oil during TACE. We considered hepatocellular carcinoma to be responsive
      to TACE when the sum of iodized oil retention in the tumor and a low-attenuation
      area on CT was greater than 50% of tumor size. We compared the frequency of
      arterioportal fistula and the rate of tumor response to TACE in both groups and
      also evaluated possible factors associated with postbiopsy arterioportal fistula,
      such as age, sex, Child-Pugh score, tumor size, average number of needle passes,
      average distance that the needle traversed normal liver before reaching the mass,
      and average interval between biopsy and TACE. RESULTS: Twenty-three (56.1%) of 41
      patients in the biopsy group and 19 (11.8%) of 161 patients in the control group
      had an arterioportal fistula (p < 0.001). The rate of tumor response to TACE was
      87.8% (36/41) in the biopsy group and 87.0% (140/161) in the control group (p =
      0.5932). Of the possible related factors, only tumor size correlated negatively
      with the occurrence of arterioportal fistula. CONCLUSION: Percutaneous liver
      biopsy in hepatocellular carcinoma patients apparently increases the rate of
      arterioportal fistula but does not seem to affect the rate of tumor response to
      TACE.

PMID- 16423969
TI  - Radiologic management of cysts in the abdomen and pelvis.
AB  - OBJECTIVE: Few abdominal or pelvic cystic lesions come to the attention of the
      interventional radiologist, and those that do are symptomatic. Differentiation of
      cysts from cystic-appearing masses is not difficult when a multitechnique imaging
      approach is used. Our objective is to summarize the principles and specifics for
      management of symptomatic cysts through percutaneous catheter techniques.
      CONCLUSION: Percutaneous aspiration of cysts can relieve symptoms without the
      need for surgery. A sound knowledge of the various types of cysts that may be
      found in the abdomen and pelvis enables the radiologist to select those patients
      who will benefit the most from percutaneous management.

PMID- 16423966
TI  - Carotid artery calcification on CT may independently predict stroke risk.
AB  - OBJECTIVE: The purpose of our study was to quantitatively evaluate calcified
      atherosclerotic burden in the cervical carotid arteries using MDCT to determine
      the relationship of scores with luminal stenosis and symptomatology. MATERIALS
      AND METHODS: Calcium plaque volume was measured in 106 cervical carotid arteries
      (53 patients) using MDCT angiography. The study group included 32 asymptomatic
      patients (mean age, 70.2 +/- 8.7 [SD] years; 15 women, 17 men) and 21 patients
      with ischemic neurologic symptoms (69.6 +/- 12.9 years; eight women, 13 men). By
      vessel, there were 43 high-grade stenotic (> or = 60% by North American
      Symptomatic Carotid Endarterectomy Trial [NASCET] criteria), 15 moderate-grade
      stenotic (30-59%), and 44 mild-grade stenotic or normal (0-29%) vessels, with
      four excluded for prior carotid endarterectomy. Volume scores were calculated by
      summing the area of calcium in the common and extracranial internal carotid
      arteries on axial slices and multiplying by the slice increment. RESULTS:
      Controlling for cardiovascular risk factors and luminal stenosis, we found that
      scores were significantly related to the occurrence of symptoms (p = 0.003). Even
      with patient age as a covariant, patients with high-grade stenosis had
      significantly higher scores than those without high-grade disease (p = 0.004).
      Moreover, quantitative burden was associated with luminal stenosis on adjusted
      multivariate analysis (p = 0.034). The specificity and positive predictive value
      for high-grade luminal narrowing were notably lower on individual vessel analysis
      than on total score analysis, likely secondary to variability in vascular
      remodeling. CONCLUSION: Calcium scores in the cervical carotid arteries may
      represent an independent marker for luminal stenosis and ischemic symptoms. A
      prospective longitudinal study examining calcium levels and morbidity may be
      warranted to examine whether burden has a role in risk stratification.

PMID- 16423970
TI  - Percutaneous radiologic gastrostomy using push-type gastrostomy tubes with CT and
      fluoroscopic guidance.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and feasibility
      of percutaneous radiologic gastrostomy with endoscopic push-type gastrostomy
      tubes using CT and fluoroscopic guidance. CONCLUSION: Percutaneous radiologic
      gastrostomy using CT and fluoroscopic guidance with push-type tubes is a safe and
      effective means of gastric feeding that has few complications and offers an
      alternative to introducer-placed gastrostomy tubes.

PMID- 16423971
TI  - High-magnification chromoscopic colonoscopy: caution needs to be exercised before
      changing screening policy.

PMID- 16423972
TI  - Previous studies on delayed enhanced MRI for the detection of cardiac
      sarcoidosis.

PMID- 16423973
TI  - Receiver operating characteristic analysis: a proper measurement for performance
      in breast cancer screening?

PMID- 16423974
TI  - Percutaneous sacroplasty for osteoporotic insufficiency fractures.

PMID- 16423976
TI  - Liver abscess formation after radiofrequency ablation in patients with
      hepatocellular carcinoma.

PMID- 16423975
TI  - PET/CT with diagnostic CT in the evaluation of childhood sarcoma.

PMID- 16423977
TI  - Inadvertent high radiation dose to pediatric patients during CT: whose
      responsibility is it?

PMID- 16423979
TI  - Why I won't be getting off the interventional radiology tour.

PMID- 16423980
TI  - True gastrogastric intussusception: a rare radiologic diagnosis with surgical
      correlation.

PMID- 16423981
TI  - Unusual manifestation of small-vessel vasculitis.

PMID- 16423982
TI  - Snooping around the adolescent pelvis: good grief, it's the brief!

PMID- 16423983
TI  - The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with
      specificity for high mannose.
AB  - We examined the carbohydrate-binding potential of the C-type lectin-like receptor
      Dectin-2 (Clecf4n). The carbohydrate-recognition domain (CRD) of Dectin-2
      exhibited cation-dependent mannose/fucose-like lectin activity, with an IC(50)
      for mannose of approximately 20 mM compared to an IC(50) of 1.5 mM for the
      macrophage mannose receptor when assayed by similar methodology. The
      extracellular domain of Dectin-2 exhibited binding to live Candida albicans and
      the Saccharomyces-derived particle zymosan. This binding was completely abrogated
      by cation chelation and was competed by yeast mannans. We compared the lectin
      activity of Dectin-2 with that of two other C-type lectin receptors (mannose
      receptor and SIGNR1) known to bind fungal mannans. Both mannose receptor and
      SIGNR1 were able to bind bacterial capsular polysaccharides derived from
      Streptococcus pneumoniae, but interestingly they exhibited distinct binding
      profiles. The Dectin-2 CRD exhibited only weak interactions to some of these
      capsular polysaccharides, indicative of different structural or affinity
      requirements for binding, when compared with the other two lectins. Glycan array
      analysis of the carbohydrate recognition by Dectin-2 indicated specific
      recognition of high-mannose structures (Man(9)GlcNAc(2)). The differences in the
      specificity of these three mannose-specific lectins indicate that mannose
      recognition is mediated by distinct receptors, with unique specificity, that are
      expressed by discrete subpopulations of cells, and this further highlights the
      complex nature of carbohydrate recognition by immune cells.

PMID- 16423984
TI  - Cranking the immunologic engine with chemotherapy: using context to drive tumor
      antigen cross-presentation towards useful antitumor immunity.
AB  - This review shows how tumor antigen cross-presentation is affected by the major
      therapeutic modalities including chemotherapy, radiotherapy, and surgery. We
      argue that this process could affect the way that a tumor works as its own
      cellular vaccine, and that it is differentially modulated by the choice of
      treatment.

PMID- 16423985
TI  - Distinct role of macrophages in different tumor microenvironments.
AB  - Macrophages are prominent in the stromal compartment of virtually all types of
      malignancy. These highly versatile cells respond to the presence of stimuli in
      different parts of tumors with the release of a distinct repertoire of growth
      factors, cytokines, chemokines, and enzymes that regulate tumor growth,
      angiogenesis, invasion, and/or metastasis. The distinct microenvironments where
      tumor-associated macrophages (TAM) act include areas of invasion where TAMs
      promote cancer cell motility, stromal and perivascular areas where TAMs promote
      metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate
      angiogenesis. This review will discuss the evidence for differential regulation
      of TAMs in these microenvironments and provide an overview of current attempts to
      target or use TAMs for therapeutic purposes.

PMID- 16423986
TI  - Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the
      growth of human PC-3 prostate xenografts in immunodeficient mice.
AB  - Earlier studies using prostate cancer cells in culture showed that phenethyl
      isothiocyanate (PEITC) and curcumin have significant chemopreventive and possibly
      chemotherapeutic effects. However, their in vivo effects are still lacking.
      Hence, this study was undertaken to determine the possible in vivo efficacy of
      prostate cancer-prevention as well as cancer-therapeutic treatment by PEITC and
      curcumin alone or in combination. We evaluated the effects on tumor growth in
      vivo, using NCr immunodeficient (nu/nu) mice bearing s.c. xenografts of PC-3
      human prostate cancer cells. Molecular biomarkers representing proliferation and
      apoptosis were determined. Continued i.p. injection of curcumin or PEITC (6 and 5
      mumol; thrice a week for 28 days), beginning a day before tumor implantation
      significantly retarded the growth of PC-3 xenografts. Combination of i.p.
      administration of PEITC (2.5 mumol) and curcumin (3 mumol) showed stronger growth
      inhibitory effects. Next, we evaluated the cancer-therapeutic potential of
      curcumin and PEITC in mice with well-established tumors, and the results showed
      that PEITC or curcumin alone had little effect, whereas combination of curcumin
      and PEITC significantly reduced the growth of PC-3 xenografts.
      Immunohistochemistry staining and Western blot analysis revealed that the
      inhibition of Akt and nuclear factor-kappaB signaling pathways could contribute
      to the inhibition of cell proliferation and induction of apoptosis. Taken
      together, our results show that PEITC and curcumin alone or in combination
      possess significant cancer-preventive activities in the PC-3 prostate tumor
      xenografts. Furthermore, we found that combination of PEITC and curcumin could be
      effective in the cancer-therapeutic treatment of prostate cancers.

PMID- 16423987
TI  - Significance of murine retroviral mutagenesis for identification of disease genes
      in human acute myeloid leukemia.
AB  - Retroviral insertion mutagenesis is considered a powerful tool to identify cancer
      genes in mice, but its significance for human cancer has remained elusive.
      Moreover, it has recently been debated whether common virus integrations are
      always a hallmark of tumor cells and contribute to the oncogenic process. Acute
      myeloid leukemia (AML) is a heterogeneous disease with a variable response to
      treatment. Recurrent cytogenetic defects and acquired mutations in regulatory
      genes are associated with AML subtypes and prognosis. Recently, gene expression
      profiling (GEP) has been applied to further risk stratify AML. Here, we show that
      mouse leukemia genes identified by retroviral insertion mutagenesis are more
      frequently differentially expressed in distinct subclasses of adult and pediatric
      AML than randomly selected genes or genes located more distantly from a virus
      integration site. The candidate proto-oncogenes showing discriminative expression
      in primary AML could be placed in regulatory networks mainly involved in signal
      transduction and transcriptional control. Our data support the validity of
      retroviral insertion mutagenesis in mice for human disease and indicate that
      combining these murine screens for potential proto-oncogenes with GEP in human
      AML may help to identify critical disease genes and novel pathogenetic networks
      in leukemia.

PMID- 16423988
TI  - HIV-1 Vpr induces DNA double-strand breaks.
AB  - Recent observations imply that HIV-1 infection induces chromosomal DNA damage
      responses. However, the precise molecular mechanism and biological relevance are
      not fully understood. Here, we report that HIV-1 infection causes double-strand
      breaks in chromosomal DNA. We further found that Vpr, an accessory gene product
      of HIV-1, is a major factor responsible for HIV-1-induced double-strand breaks.
      The purified Vpr protein promotes double-strand breaks when incubated with
      isolated nuclei, although it does not exhibit endonuclease activity in vitro. A
      carboxyl-terminally truncated Vpr mutant that is defective in DNA-binding
      activity is less capable of Vpr-dependent double-strand break formation in
      isolated nuclei. The data suggest that double-strand breaks induced by Vpr depend
      on its DNA-binding activity and that Vpr may recruit unknown nuclear factor(s)
      with positive endonuclease activity to chromosomal DNA. This is the first direct
      evidence that Vpr induces double-strand breaks in HIV-1-infected cells. We
      discuss the possible roles of Vpr-induced DNA damage in HIV-1 infection and the
      involvement of Vpr in further acquired immunodeficiency syndrome-related tumor
      development.

PMID- 16423989
TI  - Comparison of metabolic pathways between cancer cells and stromal cells in
      colorectal carcinomas: a metabolic survival role for tumor-associated stroma.
AB  - Understanding tumor metabolism is important for the development of anticancer
      therapies. Immunohistochemical evaluation of colorectal adenocarcinomas showed
      that cancer cells share common enzyme/transporter activities suggestive of an
      anaerobic metabolism [high lactate dehydrogenase 5 (LDH5)/hypoxia-inducible
      factor alphas (HIFalphas)] with high ability for glucose absorption and lactate
      extrusion [high glucose transporter 1 (GLUT1)/monocarboxylate transporter
      (MCT1)]. The tumor-associated fibroblasts expressed proteins involved in lactate
      absorption (high MCT1/MCT2), lactate oxidation (high LDH1 and low
      HIFalphas/LDH5), and reduced glucose absorption (low GLUT1). The expression
      profile of the tumor-associated endothelium indicated aerobic metabolism (high
      LDH1 and low HIFalphas/LDH5), high glucose absorption (high GLUT1), and
      resistance to lactate intake (lack of MCT1). It is suggested that the newly
      formed stroma and vasculature express complementary metabolic pathways, buffering
      and recycling products of anaerobic metabolism to sustain cancer cell survival.
      Tumors survive and grow because they are capable of organizing the regional
      fibroblasts and endothelial cells into a harmoniously collaborating metabolic
      domain.

PMID- 16423990
TI  - Ductal access for prevention and therapy of mammary tumors.
AB  - In cancer patients and in those at high risk, systemic exposure to agents for
      therapy or prevention is accompanied by undesirable side effects. We hypothesized
      that it is possible to prevent and treat breast cancer by introducing anticancer
      agents into the mammary ductal network. Here, we show the efficacy of
      intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated
      liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer
      using the rat N-methyl-N'-nitrosourea-induced and spontaneous HER-2/neu
      transgenic mouse (neu-N) models of breast cancer. Intraductal administration of
      PLD to neu-N mice caused regression of established tumors and prevented tumor
      development more effectively than i.v. injection (P < 0.0001). Intraductal
      administration resulted in lower circulating levels of PLD compared with i.v.
      administration, with no evidence of systemic toxicity or long-term
      histopathologic changes in the mammary gland. Compared with systemic
      administration, intraductal injection provides direct access to breast lesions
      with higher local and lower systemic drug exposure. These studies suggest that
      this approach has potential for application to prevention and neoadjuvant therapy
      of early breast cancer.

PMID- 16423991
TI  - The single nucleotide polymorphism IVS1+309 in mouse double minute 2 does not
      affect risk of familial breast cancer.
AB  - The mouse double minute 2 (MDM2) oncoprotein promotes cell survival and cell
      cycle progression by inhibiting the p53 tumor suppressor protein. Further, MDM2
      overexpression can inhibit DNA double-strand break repair in a p53-independent
      manner. Recently, it was shown that a single nucleotide polymorphism (SNP) in the
      MDM2 promoter was associated with an accelerated tumor formation in individuals
      with a p53 mutation. The present case-control study investigated the association
      of this SNP (IVS1+309) with the risk and the age of onset of familial breast
      cancer in patients with unknown p53 mutation status. Data from 549 women affected
      by familial breast cancer and 1,065 healthy controls were analyzed. The cases did
      not carry BRCA1/2 mutations. Cases and controls showed a similar genotype
      distribution and the SNP did not seem to modify the age of onset of familial
      breast cancer. The data were also examined taking into account the presence of
      any additional cancer after breast cancer and the family history of cases;
      however, no association was found. These results suggest that the SNP IVS1+309
      alone affects neither the risk nor the age of onset of heritable breast cancer.

PMID- 16423992
TI  - Tumor cell lines expressing the proteasome subunit isoform LMP7E1 exhibit
      immunoproteasome deficiency.
AB  - The immune system can recognize antigenic peptides derived from tumors by their
      presentation on MHC class I complexes to CTLs. Immunoproteasomes (i20S) can
      substantially enhance the MHC class I peptide repertoire, making down-regulation
      of i20S an important strategy of tumor cells in manipulating immune surveillance.
      Here, we report that human cancer cells express the nonfunctional immunosubunit
      variant LMP7E1, in addition to, or instead of LMP7E2, in response to IFN-gamma.
      This preferential expression of LMP7E1 and the consequent down-regulation of
      LMP7E2 results in i20S deficiency. The molecular explanation for this phenomenon
      is the incapacity of LMP7E1 to interact efficiently with the proteasome
      maturation protein, which regularly recruits LMP7E2 into nascent i20S precursor
      complexes. In contrast to previous reports, i20S formation in these cancer cells
      cannot be restored by IFN-gamma treatment. However, expression of LMP7E2 in these
      cells restores the i20S-deficient phenotype. Thus, our data describe a novel
      mechanism that contributes to the process of oncogenesis.

PMID- 16423993
TI  - CpG island methylation and expression of the secreted frizzled-related protein
      gene family in chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (CLL) is characterized by a clonal
      accumulation of mature neoplastic B cells indicating disruption of apoptosis.
      Restriction Landmark Genome Scanning was done to identify novel target genes
      silenced by CpG island methylation in CLL. Secreted frizzled-related protein 4
      (SFRP4), a negative regulator of the Wnt signaling pathway, was found to be
      frequently methylated in CLL samples. Wnt signaling has been shown to control
      normal apoptotic behavior and is required for normal B-cell development whereas
      aberrant activation of this pathway has been observed in CLL. We show aberrant
      DNA methylation and silencing of SFRP4, as well as of additional SFRP family
      members, in primary CLL samples. Induction of their expression in a dose
      dependent manner following treatment with a demethylating agent, 5-aza-2'
      deoxycytidine, was shown. Of the five SFRP family members studied in detail,
      SFRP1 was hypermethylated and down-regulated in all CLL patient samples studied,
      suggesting that this epigenetic event is a critical step during leukemogenesis.
      Our results suggest that silencing of SFRPs by CpG island methylation is one
      possible mechanism contributing to aberrant activation of Wnt signaling pathway
      in CLL.

PMID- 16423994
TI  - Gene conversion is a frequent mechanism of inactivation of the wild-type allele
      in cancers from MLH1/MSH2 deletion carriers.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly
      inherited cancer predisposition syndrome caused by germ line mutations in DNA
      mismatch repair genes, predominantly MLH1 and MSH2, with large genomic
      rearrangements accounting for 5% to 20% of all mutations. Although crucial to the
      understanding of cancer initiation, little is known about the second, somatic hit
      in HNPCC tumorigenesis, commonly referred to as loss of heterozygosity. Here, we
      applied a recently developed method, multiplex ligation-dependent probe
      amplification, to study MLH1/MSH2 copy number changes in 16 unrelated Swiss HNPCC
      patients, whose cancers displayed microsatellite instability and loss of MLH1 or
      MSH2 expression, but in whom no germ line mutation could be detected by
      conventional screening. The aims of the study were (a) to determine the
      proportion of large genomic rearrangements among Swiss MLH1/MSH2 mutation
      carriers and (b) to investigate the frequency and nature of loss of
      heterozygosity as a second, somatic event, in tumors from MLH1/MSH2 germ line
      deletion carriers. Large genomic deletions were found to account for 4.3% and
      10.7% of MLH1 and MSH2 mutations, respectively. Multiplex ligation-dependent
      probe amplification analysis of 18 cancer specimens from two independent sets of
      Swiss and Finnish MLH1/MSH2 deletion carriers revealed that somatic mutations
      identical to the ones in the germ line occur frequently in colorectal cancers (6
      of 11; 55%) and are also present in extracolonic HNPCC-associated tumors.
      Chromosome-specific marker analysis implies that loss of the wild-type allele
      predominantly occurs through locus-restricted recombinational events, i.e., gene
      conversion, rather than mitotic recombination or deletion of the respective gene
      locus. (Cancer Res 2006; (66)2: 659-64).

PMID- 16423995
TI  - PEG10 is a c-MYC target gene in cancer cells.
AB  - The product of the imprinted gene paternally expressed gene-10 (PEG10) has been
      reported to support proliferation in hepatocellular carcinomas, but how this gene
      is regulated has been an open question. We find that MYC knockdown by RNA
      interference suppresses PEG10 expression in Panc1 pancreatic carcinoma and HepG2
      hepatocellular carcinoma cells and that knockdown of PEG10 inhibits the
      proliferation of Panc1, HepG2, and Hep3B cells. Conversely, PEG10 was up
      regulated by inducing c-MYC expression in a B-lymphocyte cell line. Chromatin
      immunoprecipitation from Panc1 cells showed c-MYC bound to an E-box-containing
      region in the PEG10 first intron and site-directed mutagenesis showed that the
      most proximal E-box is essential for promoter activity. In a mouse mammary tumor
      virus (MMTV)-MYC transgenic mouse model of breast cancer, most but not all of the
      mammary carcinomas had strongly increased Peg10 mRNA compared with normal mammary
      gland. By immunohistochemistry, normal human breast and prostate epithelium was
      negative for the major isoform [reading frame-1 (RF1)] of PEG10 protein, but this
      cytoplasmic protein was strongly expressed in a subset of breast carcinomas in
      situ and invasive ductal carcinomas ( approximately 30%) and in a similar
      percentage of prostate cancers. As in the mouse model, we found positive, but not
      absolute, correlations between PEG10 and c-MYC in tissue arrays containing 161
      human breast cancers (P < 0.002) and 30 prostate cancers (P = 0.014).
      Immunostaining of human placenta showed PEG10 and c-MYC proteins coexpressed in
      proliferating cytotrophoblast and coordinately lost in postmitotic
      syncytiotrophoblast. These findings link cancer genetics and epigenetics by
      showing that a classic proto-oncogene, MYC, acts directly upstream of a
      proliferation-positive imprinted gene, PEG10.

PMID- 16423996
TI  - c-myc overexpression causes anaplasia in medulloblastoma.
AB  - Both anaplasia and increased c-myc gene expression have been shown to be negative
      prognostic indicators for survival in medulloblastoma patients. myc gene
      amplification has been identified in many large cell/anaplastic medulloblastoma,
      but no causative link between c-myc and anaplastic changes has been established.
      To address this, we stably overexpressed c-myc in two medulloblastoma cell lines,
      DAOY and UW228, and examined the changes in growth characteristics. When analyzed
      in vitro, cell lines with increased levels of c-myc had higher rates of growth
      and apoptosis as well as significantly improved ability to form colonies in soft
      agar compared with control. When injected s.c. into nu/nu mice, flank xenograft
      tumors with high levels of c-myc in DAOY cell line background were 75% larger
      than those derived from control. Overexpression of c-myc was required for tumor
      formation by UW228 cells. Most remarkably, the histopathology of the Myc tumors
      was severely anaplastic, with large areas of necrosis/apoptosis, increased
      nuclear size, and macronucleoli. Indices of proliferation and apoptosis were also
      significantly higher in Myc xenografts. Thus, c-myc seems to play a causal role
      in inducing anaplasia in medulloblastoma. Because anaplastic changes are often
      observed in recurrent medulloblastoma, we propose that c-myc dysregulation is
      involved in the progression of these malignant embryonal neoplasms.

PMID- 16423997
TI  - De novo CpG island methylation in human cancer cells.
AB  - A major obstacle toward understanding how patterns of abnormal mammalian cytosine
      DNA methylation are established is the difficulty in quantitating the de novo
      methylation activities of DNA methyltransferases (DNMT) thought to catalyze these
      reactions. Here, we describe a novel method, using native human CpG island
      substrates from genes that frequently become hypermethylated in cancer, which
      generates robust activity for measuring de novo CpG methylation. We then survey
      colon cancer cells with genetically engineered deficiencies in different DNMTs
      and find that the major activity against these substrates in extracts of these
      cells is DNMT1, with minor contribution from DNMT 3b and none from DNMT3a, the
      only known bona fide de novo methyltransferases. The activity of DNMT1 against
      unmethylated CpG rich DNA was further tested by introducing CpG island substrates
      and DNMT1 into Drosophila melanogaster cells. The exogenous DNMT1 methylates the
      integrated mammalian CpG islands but not the Drosophila DNA. Additionally, in
      human cancer cells lacking DNMT1 and DNMT3b and having nearly absent genomic
      methylation, gene-specific de novo methylation can be initiated by reintroduction
      of DNMT1. Our studies provide a new assay for de novo activity of DNMTs and data
      suggesting a potential role for DNMT1 in the initiation of promoter CpG island
      hypermethylation in human cancer cells.

PMID- 16423998
TI  - A functional variant in the transcriptional regulatory region of gene LOC344967
      cosegregates with disease phenotype in familial nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma is a common malignancy in Southeast Asian countries, and
      genetic background is a well-known component of the complexity underlying its
      tumorigenic process. We have mapped a nasopharyngeal carcinoma susceptibility
      locus to chromosome 4p15.1-q12 in a previous linkage study on nasopharyngeal
      carcinoma pedigrees. In this study provided in this communication, we screened
      all the genes in this region, with a focus on exons, promoters, and the exon
      intron boundary to identify nasopharyngeal carcinoma-associated mutations or
      functional variants. Importantly, we found a novel gene (LOC344967) with a single
      nucleotide polymorphism -32G/A in the promoter region. This gene is a member of
      the acyl CoA thioesterase family that plays an important role in fatty acid
      metabolism and is involved in the progression of various types of tumors. The 
      32A variant was found cosegregated with the disease phenotype in the
      nasopharyngeal carcinoma pedigrees that we previously used for the linkage study.
      Moreover, this -32A variant creates an activator protein (AP-1)-binding site in
      the transcriptional regulatory region of LOC344967, which significantly enhanced
      the binding of AP-1 to the promoter region and the transcription activity of the
      promoter in vivo. Furthermore, the expression of LOC344967 was significantly up
      regulated at both mRNA and protein levels in nasopharyngeal carcinoma cells
      sharing the -32G/A genotype compared with nasopharyngeal carcinoma cells with the
      -32G/G genotype. Collectively, these results provide evidence that the -32A
      variant is a functional sequence change and may be related to nasopharyngeal
      carcinoma susceptibility in the families studied.

PMID- 16423999
TI  - Thymosin beta4 is a determinant of the transformed phenotype and invasiveness of
      S-adenosylmethionine decarboxylase-transfected fibroblasts.
AB  - S-adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the synthesis of
      polyamines essential for cell growth and proliferation. Its overexpression
      induces the transformation of murine fibroblasts in both sense and antisense
      orientations, yielding highly invasive tumors in nude mice. These cell lines
      hence provide a good model to study cell invasion. Here, the gene expression
      profiles of these cells were compared with their normal counterpart by microarray
      analyses (Incyte Genomics, Palo Alto, CA, and Affymetrix, Santa Clara, CA). Up
      regulation of the actin sequestering molecule thymosin beta4 was the most
      prominent change in both cell lines. Tetracycline-inducible expression of
      thymosin beta4 antisense RNA caused a partial reversal of the transformed
      phenotype. Further, reversal of transformation by dominant-negative mutant of c
      Jun (TAM67) caused reduction in thymosin beta4 mRNA. Interestingly, a sponge
      toxin, latrunculin A, which inhibits the binding of thymosin beta4 to actin, was
      found to profoundly affect the morphology and proliferation of the AdoMetDC
      transformants and to block their invasion in three-dimensional Matrigel. Thus,
      thymosin beta4 is a determinant of AdoMetDC-induced transformed phenotype and
      invasiveness. Up-regulation of thymosin beta4 was also found in ras-transformed
      fibroblasts and metastatic human melanoma cells. These data encourage testing
      latrunculin A-like and other agents interfering with thymosin beta4 for treatment
      of thymosin beta4-overexpressing tumors with high invasive and metastatic
      potential.

PMID- 16424000
TI  - Protein kinase C delta overexpressing transgenic mice are resistant to chemically
      but not to UV radiation-induced development of squamous cell carcinomas: a
      possible link to specific cytokines and cyclooxygenase-2.
AB  - Protein kinase C delta (PKCdelta), a Ca(2+)-independent, phospholipid-dependent
      serine/threonine kinase, is among the novel PKCs (delta, epsilon, and eta)
      expressed in mouse epidermis. We reported that FVB/N transgenic mice that
      overexpress ( approximately 8-fold) PKCdelta protein in basal epidermal cells and
      cells of the hair follicle are resistant to the development of both skin
      papillomas and squamous cell carcinoma (SCC) elicited by 7,12
      dimethylbenz(a)anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate
      (TPA) promotion protocol. We now present that PKCdelta overexpression in
      transgenic mice failed to suppress the induction of SCC developed by repeated
      exposures to UV radiation (UVR), the environmental carcinogen linked to the
      development of human SCC. Both TPA and UVR treatment of wild-type mice (a)
      increased the expression of proliferating cell nuclear antigen (PCNA) and
      apoptosis; (b) stimulated the expression of cytokines tumor necrosis factor-alpha
      (TNF-alpha), granulocyte macrophage colony-stimulating factor (GM-CSF), and
      granulocyte CSF (G-CSF); and (c) increased cyclooxygenase-2 (COX-2) expression
      and expression of phosphorylated Akt (p-Akt), p38, extracellular signal-regulated
      kinase-1 (ERK1), and ERK2. PKCdelta overexpression in transgenic mice enhanced
      TPA-induced but not UVR-induced apoptosis and suppressed TPA-stimulated but not
      UVR-stimulated levels of cell PCNA, cytokines (TNF-alpha, G-CSF, and GM-CSF), and
      the expression of COX-2, p-Akt, and p38. The results indicate that UVR-mediated
      signal transduction pathway to the induction of SCC does not seem to be sensitive
      to PKCdelta overexpression. The proapoptotic activity of PKCdelta coupled with
      its ability to suppress TPA-induced expression of proinflammatory cytokines, COX
      2 expression, and the phosphorylation of Akt and p38 may play roles in the
      suppression of TPA-promoted development of SCC.

PMID- 16424001
TI  - TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving antagonistic
      activity of Chibby.
AB  - The Wnt/beta-catenin pathway has been implicated in human cancers. Here, we show
      that TC1 (C8orf4), a small protein present in vertebrates, functions as a
      positive regulator of the pathway. TC1 interacts with Chibby (Cby) and thereby
      enhances the signaling pathway by relieving the antagonistic function of Cby on
      the beta-catenin-mediated transcription. Upon coexpression in mammalian cells,
      TC1 redistributes from nucleolus to nuclear speckles, where it colocalizes with
      Cby. TC1 up-regulates the expression of beta-catenin target genes that are
      implicated in invasiveness and aggressive behavior of cancers, such as
      metalloproteinases, laminin gamma2, and others. Our data indicate that TC1 is a
      novel upstream regulator of the Wnt/beta-catenin pathway that enhances aggressive
      behavior of cancers.

PMID- 16424002
TI  - Differential requirement for DNA methyltransferase 1 in maintaining human cancer
      cell gene promoter hypermethylation.
AB  - Previous work has shown that DNA hypermethylation of tumor suppressor genes in
      colorectal cancer cells may be maintained in the absence of the major mammalian
      methyltransferase, DNA methyltransferase 1 (DNMT1). In an effort to dissect the
      dependency on DNMT1 to maintain such hypermethylation in different cancer types,
      we performed a systematic analysis of depletion of DNMT1 in colorectal (SW48),
      bladder (T24), and breast (T47D) cancer cells by DNMT1-specific small hairpin RNA
      (shRNA) targeting. We show that although DNMT1-deficient SW48 and T24 cells
      exhibited no observable growth defects and were able to maintain promoter
      hypermethylation, DNMT1-deficient T47D breast cells failed to form comparable
      numbers of colonies when stably selected for the incorporation of the DNMT1
      specific shRNA expression vector, suggesting a growth defect with reduced levels
      of DNMT1. Further treatment of T47D cells with transient transfection of small
      interfering RNA targeting DNMT1 revealed that severely DNMT1-deficient T47D cells
      could not fully maintain promoter hypermethylation, and gene silencing was
      partially reversed at two of the three assayed loci. These observations suggest
      that human cancer cells may differ in their reliance on DNMT1 for maintaining DNA
      methylation.

PMID- 16424003
TI  - PTEN autoregulates its expression by stabilization of p53 in a phosphatase
      independent manner.
AB  - PTEN (phosphatase and tensin homologue, deleted on chromosome 10) is a tumor
      suppressor with dual phosphatase activity and mutations of its gene, PTEN, have
      been associated with many sporadic cancers and heritable neoplasia syndromes,
      including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. However,
      accumulating evidence now shows that PTEN may have novel functions other than as
      a phosphatase. In the present study, we show that PTEN is able to autoregulate
      its expression through the stabilization of another tumor suppressor p53. We
      further show that PTEN enhances p53 transactivation, a relationship that requires
      the interaction between PTEN and p53 and is PTEN phosphatase independent. We show
      that cell lines from Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome
      patients with germ line PTEN promoter mutations in the vicinity of the p53
      binding motifs have altered p53 regulation. This seems to be due to reduced PTEN
      stability and decreased PTEN-p53 interactions. Our data provide clues to better
      understand the regulation of PTEN expression and the possible mechanisms of the
      pathogenesis of the subset of Cowden syndrome individuals with germ line promoter
      variation and who lack mutations in the PTEN coding region and splice sites.
      Importantly, this mechanism also holds for those sporadic tumors that lack
      intragenic mutations but have hemizygous deletion of PTEN, which includes the
      promoter region as manifested by loss-of-heterozygosity of 10q markers. The
      importance of our observations is underlined by the broad spectrum of neoplasias
      that harbor somatic PTEN or p53 alterations, or both.

PMID- 16424004
TI  - Profiling genetic variation along the androgen biosynthesis and metabolism
      pathways implicates several single nucleotide polymorphisms and their
      combinations as prostate cancer risk factors.
AB  - Several candidate genes along androgen pathway have been suggested to affect
      prostate cancer risk but no single gene seems to be overwhelmingly important for
      a large fraction of the patients. In this study, we first screened for variants
      in candidate genes and then chose to explore the association between 18 variants
      and prostate cancer risk by genotyping DNA samples from unselected (n = 847) and
      familial (n = 121) prostate cancer patients and population controls (n = 923). We
      identified a novel single nucleotide polymorphism (SNP) in the CYP19A1 gene,
      T201M, with a mild significant association with prostate cancer [odds ratio (OR),
      2.04; 95% confidence interval (95% CI), 1.03-4.03; P = 0.04]. Stratified analysis
      revealed that this risk was most apparent in patients with organ-confined (T(1)
      T(2)) and low-grade (WHO grade 1) tumors (OR, 5.42; 95% CI, 2.33-12.6; P <
      0.0001). In contrast, CYP17A1 -34T>C alteration was associated with moderate to
      poorly differentiated (WHO grade 2-3) organ-confined disease (OR, 1.42; 95% CI,
      1.09-1.83; P = 0.007). We also tested a multigenic model of prostate cancer risk
      by calculating the joint effect of CYP19A1 T201M with five other common SNPs.
      Individuals carrying both the CYP19A1 and KLK3 -252A>G variant alleles had a
      significantly increased risk for prostate cancer (OR, 2.87; 95% CI, 1.10-7.49; P
      = 0.03). In conclusion, our results suggest that several SNPs along the androgen
      pathway, especially in CYP19A1 and CYP17A1, may influence prostate cancer
      development and progression. These genes may have different contributions to
      distinct clinical subsets as well as combinatorial effects in others illustrating
      that profiling and joint analysis of several genes along each pathway may be
      needed to understand genetic contributions to prostate cancer etiology.

PMID- 16424005
TI  - Critical roles for polymerase zeta in cellular tolerance to nitric oxide-induced
      DNA damage.
AB  - Nitric oxide (NO), a signal transmitter involved in inflammation and regulation
      of smooth muscle and neurons, seems to cause mutagenesis, but its mechanisms have
      remained elusive. To gain an insight into NO-induced genotoxicity, we analyzed
      the effect of NO on a panel of chicken DT40 clones deficient in DNA repair
      pathways, including base and nucleotide excision repair, double-strand break
      repair, and translesion DNA synthesis (TLS). Our results show that cells
      deficient in Rev1 and Rev3, a subunit essential for DNA polymerase zeta
      (Polzeta), are hypersensitive to killing by two chemical NO donors, spermine
      NONOate and S-nitroso-N-acetyl-penicillamine. Mitotic chromosomal analysis
      indicates that the hypersensitivity is caused by a significant increase in the
      level of induced chromosomal breaks. The data reveal the critical role of TLS
      polymerases in cellular tolerance to NO-induced DNA damage and suggest the
      contribution of these error-prone polymerases to accumulation of single base
      substitutions.

PMID- 16424006
TI  - In utero exposure of mice to dibenzo[a,l]pyrene produces lymphoma in the
      offspring: role of the aryl hydrocarbon receptor.
AB  - Lymphoma and leukemia are the most common cancers in children and young adults;
      in utero carcinogen exposure may contribute to the etiology of these cancers. A
      polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DBP), was given to
      pregnant mice (15 mg/kg body weight, gavage) on gestation day 17. Significant
      mortalities in offspring, beginning at 12 weeks of age, were observed due to an
      aggressive T-cell lymphoblastic lymphoma. Lymphocytes invaded numerous tissues.
      All mice surviving 10 months, exposed in utero to DBP, exhibited lung tumors;
      some mice also had liver tumors. To assess the role of the aryl hydrocarbon
      receptor (AHR) in DBP transplacental cancer, B6129SF1/J (AHR(b-1/d), responsive)
      mice were crossed with strain 129S1/SvIm (AHR(d/d), nonresponsive) to determine
      the effect of maternal and fetal AHR status on carcinogenesis. Offspring born to
      nonresponsive mothers had greater susceptibility to lymphoma, irrespective of
      offspring phenotype. However, when the mother was responsive, an AHR-responsive
      phenotype in offspring increased mortality by 2-fold. In DBP-induced lymphomas,
      no evidence was found for TP53, beta-catenin, or Ki-ras mutations but lung
      adenomas of mice surviving to 10 months of age had mutations in Ki-ras codons 12
      and 13. Lung adenomas exhibited a 50% decrease and a 35-fold increase in
      expression of Rb and p19/ARF mRNA, respectively. This is the first demonstration
      that transplacental exposure to an environmental PAH can induce a highly
      aggressive lymphoma in mice and raises the possibility that PAH exposures to
      pregnant women could contribute to similar cancers in children and young adults.

PMID- 16424007
TI  - Altered expression and localization of creatine kinase B, heterogeneous nuclear
      ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix
      associated with colon cancer.
AB  - Identification of biomarkers could lead to the development of effective screening
      tests for colorectal cancer. A previous study from our laboratory showed specific
      alterations of nuclear structure in colon cancer. In an effort to characterize
      these biomarkers, protein spots were selected from separations made by two
      dimensional gel electrophoresis, which were analyzed by mass spectrometry. The
      sequences obtained from the isolated spots revealed that they have close
      similarity to creatine kinase B (CKB) isoforms, heterogeneous nuclear
      ribonucleoprotein F (hnRNP F) and high mobility group box 1 protein (HMGB1)
      isoforms. To determine the expression of these proteins in colon cancer,
      expression was studied in 9 tumor and matched adjacent normal pairs, 5 donor
      colons, 16 polyps, 4 metastatic liver lesions and matched adjacent normal pairs,
      and 3 liver donors. CKB and hnRNP F were expressed in 78% and 89% of colon
      tumors, respectively. hnRNP F had a higher frequency of expression than CKB in
      premalignant polyps. With the establishment of differential expression of the
      proteins in colon cancer, their subcellular localization was analyzed. The
      subcellular fractions studied both showed high protein levels of hnRNP F in colon
      tumors compared with normal colon tissues. Surprisingly, subcellular levels of
      CKB were decreased in colon tumors, suggesting that the observed high CKB levels
      in nuclear matrix extracts are caused by the enhanced localization of CKB to the
      nuclear matrix during colon tumorigenesis. These results suggest an involvement
      of hnRNP F and CKB in colorectal cancer. Additionally, they suggest that hnRNP F
      is a potential marker for colorectal cancer progression.

PMID- 16424008
TI  - Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha
      in cancer: role of free radical formation.
AB  - Widespread expression of the alpha-subunit of hypoxia-inducible factor (HIF
      1alpha) was observed in samples of human oral squamous cell carcinoma. In all the
      cases, this was accompanied by a widespread distribution of nitric oxide (NO)
      synthases (NOS). Furthermore, in three human cell lines derived from human oral
      squamous cell carcinoma, the accumulation of HIF-1alpha was prevented either by
      inhibition of NOS activity with the nonspecific NOS inhibitor N(G)-monomethyl-L
      arginine or by the antioxidants N-acetyl-L-cysteine and ascorbic acid. We suggest
      that, in certain forms of cancer, NO might be responsible for the accumulation of
      HIF-1alpha by a mechanism dependent on free radicals.

PMID- 16424009
TI  - Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease
      2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling
      pathway.
AB  - Accumulating evidence reveals a significant correlation between angiopoietin 2
      (Ang2) expression and tumor invasion and metastasis in various human cancers, but
      the major focus of recent studies has been on the angiogenic effects of Ang2. We
      recently reported that Ang2-stimulated glioma cell invasion results from the up
      regulation and activation of matrix metalloprotease 2 (MMP-2) in tumor cells. In
      this study, we identify a novel mechanism by which Ang2 stimulates MMP-2
      expression leading to glioma cell invasion. We show that Ang2 interacts with
      alpha(v)beta(1) integrin in Tie2-deficient human glioma cells, activating focal
      adhesion kinase (FAK), p130(Cas), extracellular signal-regulated protein kinase
      (ERK) 1/2, and c-jun NH(2)-terminal kinase (JNK) and substantially enhancing MMP
      2 expression and secretion. The Ang2/alpha(v)beta(1) integrin signaling pathway
      was attenuated by functional inhibition of beta(1) and alpha(v) integrins, FAK,
      p130(Cas), ERK1/2, and JNK. Furthermore, expression of a negative regulator of
      FAK, FAK-related nonkinase, by U87MG/Ang2-expressing glioma xenografts suppressed
      Ang2-induced MMP-2 expression and glioma cell infiltration in the murine brain.
      These data establish a functional link between Ang2 interaction with
      alpha(v)beta(1) integrin and glioma cell invasion through the
      FAK/p130(Cas)/ERK1/2 and JNK-mediated signaling pathway.

PMID- 16424010
TI  - Phospholipase D prevents etoposide-induced apoptosis by inhibiting the expression
      of early growth response-1 and phosphatase and tensin homologue deleted on
      chromosome 10.
AB  - Phospholipase D (PLD) has emerged as a critical regulator of cell proliferation
      and survival signaling. We show for the first time that elevated expression of
      PLD isozymes attenuates expression of the tumor suppressors early growth response
      1 (Egr-1) and the phosphatase and tensin homologue deleted on chromosome 10
      (PTEN) tumor suppressor and apoptosis during etoposide treatment. When formation
      of phosphatidic acid was inhibited by overexpression of catalytically inactive
      PLD during etoposide treatment, expression of Egr-1 and PTEN and the apoptotic
      effect of etoposide were not inhibited. This suggests that PLD inhibits
      expression of these tumor suppressors and inhibits apoptosis. Deletion of a
      specific Egr-1-binding site present in the PTEN promoter blocked etoposide
      induced PTEN activity and elevated expression of PLD decreased the sensitivity to
      apoptosis induced by ectopic expression of Egr-1. Etoposide-induced activation of
      Akt was potentiated by overexpression of PLD and PLD-stimulated suppression of
      Egr-1 was blocked by inhibition of phosphatidylinositol 3-kinase/Akt survival
      pathway at the both transcriptional and posttranscriptional levels. These results
      show that survival signals generated by PLD attenuate expression of Egr-1 by
      activation of phosphatidylinositol 3-kinase signaling pathway and induction of
      PTEN by Egr-1, which confers resistance to apoptosis.

PMID- 16424011
TI  - The gene expression program of prostate fibroblast senescence modulates
      neoplastic epithelial cell proliferation through paracrine mechanisms.
AB  - The greatest risk factor for developing carcinoma of the prostate is advanced
      age. Potential molecular and physiologic contributors to the frequency of cancer
      occurrence in older individuals include the accumulation of somatic mutations
      through defects in genome maintenance, epigenetic gene silencing, oxidative
      stress, loss of immune surveillance, telomere dysfunction, chronic inflammation,
      and alterations in tissue microenvironment. In this context, the process of
      prostate carcinogenesis can be influenced through interactions between intrinsic
      cellular alterations and the extrinsic microenvironment and macroenvironment,
      both of which change substantially as a consequence of aging. In this study, we
      sought to characterize the molecular alterations that occur during the process of
      prostate fibroblast senescence to identify factors in the aged tissue
      microenvironment capable of promoting the proliferation and potentially the
      neoplastic progression of prostate epithelium. We evaluated three mechanisms
      leading to cell senescence: oxidative stress, DNA damage, and replicative
      exhaustion. We identified a consistent program of gene expression that includes a
      subset of paracrine factors capable of influencing adjacent prostate epithelial
      growth. Both direct coculture and conditioned medium from senescent prostate
      fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold,
      respectively. The paracrine-acting proteins fibroblast growth factor 7,
      hepatocyte growth factor, and amphiregulin (AREG) were elevated in the
      extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone
      stimulated prostate epithelial cell growth, and neutralizing antibodies and small
      interfering RNA targeting AREG attenuated, but did not completely abrogate the
      growth-promoting effects of senescent fibroblast conditioned medium. These
      results support the concept that aging-related changes in the prostate
      microenvironment may contribute to the progression of prostate neoplasia.

PMID- 16424012
TI  - The possible role of EWS-Fli1 in evasion of senescence in Ewing family tumors.
AB  - The chromosomal translocation t(11;22) yields the EWS-Fli1 fusion gene and is
      associated with oncogenesis of Ewing family tumors (EFT). In this study, using
      the RNA interference method, we show that EWS-Fli1-targeting small interfering
      RNAs (siRNA) depleted EWS-Fli1 protein and caused growth inhibition in EFT cells
      with the accumulation of p27 protein and the down-regulation of Skp2 protein in
      dose-dependent, time-dependent, and sequence-specific manners. Depletion of EWS
      Fli1 subacutely elicited a senescence-like phenotype, but not apoptosis, in EFT
      cells. Furthermore, not only the knockdown of p27, but also the forced expression
      of Skp2, reduced the expression levels of p27 protein and partially rescued
      senescence-like phenotype caused by EWS-Fli1-targeting siRNAs. The accumulation
      of p27 protein in EWS-Fli1-depleted cells inhibited cdk2 kinase activity and was
      related to the stability of p27 protein, which resulted from a decrease in Skp2
      protein. Immunohistochemical analysis of p27 and Skp2 proteins in EFT samples
      revealed that there was an inverse relationship between the expression profiles
      of p27 and Skp2 proteins. These findings indicate an important role of EWS-Fli1
      in the prevention of senescence, leading to the unlimited growth and oncogenesis
      of EFT cells through a decrease in the stability of p27 protein due to increased
      action of Skp2-mediated 26S proteasome degradation.

PMID- 16424013
TI  - Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human.
AB  - c-Maf translocation or overexpression has been observed in human multiple
      myeloma. Although c-maf might function as an oncogene in multiple myeloma, a role
      for this gene in other cancers has not been shown. In this study, we have found
      that mice transgenic for c-Maf whose expression was direct to the T-cell
      compartment developed T-cell lymphoma. Moreover, we showed that cyclin D2,
      integrin beta(7), and ARK5 were up-regulated in c-Maf transgenic lymphoma cells.
      Furthermore, 60% of human T-cell lymphomas (11 of 18 cases), classified as
      angioimmunoblastic T-cell lymphoma, were found to express c-Maf. These results
      suggest that c-Maf might cause a type of T-cell lymphoma in both mice and humans
      and that ARK5, in addition to cyclin D2 and integrin beta(7), might be downstream
      target genes of c-Maf leading to malignant transformation.

PMID- 16424014
TI  - Down-regulation of stem cell genes, including those in a 200-kb gene cluster at
      12p13.31, is associated with in vivo differentiation of human male germ cell
      tumors.
AB  - Adult male germ cell tumors (GCTs) comprise distinct groups: seminomas and
      nonseminomas, which include pluripotent embryonal carcinomas as well as other
      histologic subtypes exhibiting various stages of differentiation. Almost all GCTs
      show 12p gain, but the target genes have not been clearly defined. To identify
      12p target genes, we examined Affymetrix (Santa Clara, CA) U133A+B microarray (
      approximately 83% coverage of 12p genes) expression profiles of 17 seminomas, 84
      nonseminoma GCTs, and 5 normal testis samples. Seventy-three genes on 12p were
      significantly overexpressed, including GLUT3 and REA (overexpressed in all GCTs)
      and CCND2 and FLJ22028 (overexpressed in all GCTs, except choriocarcinomas). We
      characterized a 200-kb gene cluster at 12p13.31 that exhibited coordinated
      overexpression in embryonal carcinomas and seminomas, which included the known
      stem cell genes NANOG, STELLA, and GDF3 and two previously uncharacterized genes.
      A search for other coordinately regulated genomic clusters of stem cell genes did
      not reveal any genomic regions similar to that at 12p13.31. Comparison of
      embryonal carcinoma with seminomas revealed relative overexpression of several
      stem cell-associated genes in embryonal carcinoma, including several core
      "stemness" genes (EBAF, TDGF1, and SOX2) and several downstream targets of WNT,
      NODAL, and FGF signaling (FGF4, NODAL, and ZFP42). Our results indicate that 12p
      gain is a functionally relevant change leading to activation of proliferation and
      reestablishment/maintenance of stem cell function through activation of key stem
      cell genes. Furthermore, the differential expression of core stem cell genes may
      explain the differences in pluripotency between embryonal carcinomas and
      seminomas.

PMID- 16424016
TI  - Protein kinase C-delta and mitogen-activated protein/extracellular signal
      regulated kinase-1 control GLI activation in hedgehog signaling.
AB  - One third of all lethal cancers are associated with excessive activation of the
      Hedgehog (HH) pathway by mutations of its signaling components or by increased
      responsiveness of cells to the HH ligand. HH signaling through the GLI
      transcription factors leads to increased cell proliferation by up-regulation of
      the extracellular regulated kinase (ERK) pathway and by expression of S phase
      cyclins. In this study, we have tested the hypothesis that the HH pathway can
      integrate ERK signaling to modulate the activity of GLI. Using NIH 3T3 cells, we
      show that phorbol esters, acting through protein kinase C-delta (PKCdelta) and
      mitogen-activated protein/extracellular signal-regulated kinase-1 (MEK-1), fully
      stimulate the transcriptional activity of endogenous and overexpressed GLI
      proteins, as assessed by GLI-luciferase reporter assays, and induce the
      expression of endogenous GLI1 and PTCH-1 target genes, as assessed by reverse
      transcription-PCR. Moreover, activation of GLI elicited by Sonic Hedgehog also
      requires PKCdelta and MEK-1 function. Remarkably, coexpression of activated MEK-1
      and GLI1 or GLI2 induced a 10-fold synergistic increase in GLI-luciferase
      activity that was totally blocked by PD98059. The NH(2)-terminal region of GLI1
      (amino acids 1-130) is required for sensing the ERK pathway, as deletion of this
      domain produces active GLI1 protein with greatly reduced response to activation
      by MEK-1. Basic fibroblast growth factor activation of the ERK pathway also
      stimulated GLI1 activity through its NH(2)-terminal domain. Our results identify
      PKCdelta and MEK-1 as essential, positive regulators of GLI-mediated HH
      signaling. Furthermore, our findings suggest that tumors with deregulated HH and
      ERK synergize to stimulate cell proliferation pathways.

PMID- 16424018
TI  - MSF-A interacts with hypoxia-inducible factor-1alpha and augments hypoxia
      inducible factor transcriptional activation to affect tumorigenicity and
      angiogenesis.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the signaling
      pathway that controls the hypoxic responses of cancer cells. Activation of the
      HIF system has been observed in carcinogenesis and numerous cancers. We found an
      interaction between a member of the mammalian septin gene family (MSF-A) and the
      HIF system. MSF-A is a nuclear protein that interacts with HIF-1alpha protein to
      prevent its ubiquitination and degradation, thus activating the HIF
      transcriptome. Cells overexpressing MSF-A protein exhibit increased HIF
      transcriptional activity and higher proliferation rates in vitro and in vivo.
      Xenograft-derived human tumors from these cells were larger and more vascular.
      These findings link a function of a septin protein with angiogenesis through
      activation of the HIF pathway.

PMID- 16424015
TI  - Helicobacter infection is required for inflammation and colon cancer in SMAD3
      deficient mice.
AB  - Accumulating evidence suggests that intestinal microbial organisms may play an
      important role in triggering and sustaining inflammation in individuals afflicted
      with inflammatory bowel disease (IBD). Moreover, individuals with IBD are at
      increased risk for developing colorectal cancer, suggesting that chronic
      inflammation may initiate genetic or epigenetic changes associated with cancer
      development. We tested the hypothesis that bacteria may contribute to the
      development of colon cancer by synergizing with defective transforming growth
      factor-beta (TGF-beta) signaling, a pathway commonly mutated in human colon
      cancer. Although others have reported that mice deficient in the TGF-beta
      signaling molecule SMAD3 develop colon cancer, we found that SMAD3-deficient mice
      maintained free of the Gram-negative enterohepatic bacteria Helicobacter spp. for
      up to 9 months do not develop colon cancer. Furthermore, infection of SMAD3(-/-)
      mice with Helicobacter triggers colon cancer in 50% to 66% of the animals. Using
      real-time PCR, we found that Helicobacter organisms concentrate in the cecum, the
      preferred site of tumor development. Mucinous adenocarcinomas develop 5 to 30
      weeks after infection and are preceded by an early inflammatory phase, consisting
      of increased proliferation of epithelial cells; increased numbers of
      cyclooxygenase-2-positive cells, CD4(+) T cells, macrophages; and increased MHC
      class II expression. Colonic tissue revealed increased transcripts for the
      oncogene c-myc and the proinflammatory cytokines interleukin-1alpha (IL-1alpha),
      IL-1beta, IL-6, IFN-gamma, and tumor necrosis factor-alpha, some of which have
      been implicated in colon cancer. These results suggest that bacteria may be
      important in triggering colorectal cancer, notably in the context of gene
      mutations in the TGF-beta signaling pathway, one of the most commonly affected
      cellular pathways in colorectal cancer in humans.

PMID- 16424017
TI  - Roles of myofibroblasts in prostaglandin E2-stimulated intestinal epithelial
      proliferation and angiogenesis.
AB  - Prostaglandins (PG) are produced throughout the gastrointestinal tract and are
      critical mediators for a complex array of physiologic and pathophysiologic
      processes in the intestine. Intestinal myofibroblasts, which express
      cyclooxygenase (COX) and generate PGE(2), play important roles in intestinal
      epithelial proliferation, differentiation, inflammation, and neoplasia through
      secreting growth factors and cytokines. Here, we show that PGE(2) activated human
      intestinal subepithelial myofibroblasts (18Co) through Gs protein-coupled E
      prostanoid receptors and the cyclic AMP/protein kinase A pathway. 18Co cells and
      primary colonic myofibroblast isolates expressed a number of growth factors;
      several of them were dramatically regulated by PGE(2). An epidermal growth factor
      like growth factor, amphiregulin (AR), which was not expressed by untreated
      cells, was strongly induced by PGE(2). Expression of vascular endothelial growth
      factor A (VEGFA) was rapidly increased by PGE(2) exposure. Hepatocyte growth
      factor (HGF) was elevated in PGE(2)-treated myofibroblasts at both mRNA and
      protein levels. Thus, PGE(2)-activated myofibroblasts promoted the proliferation
      and migration of intestinal epithelial cells, which were attenuated by
      neutralizing antibodies to AR and HGF, respectively. Moreover, in the presence of
      PGE(2), myofibroblasts strongly stimulated the migration and tubular formation of
      vascular endothelial cells. Neutralizing antibody to VEGFA inhibited the observed
      stimulation of migration. These results suggest that myofibroblast-generated
      growth factors are important mediators for PGE(2)-induced intestinal epithelial
      proliferation and angiogenesis, which play critical roles in intestinal
      homeostasis, inflammation, and neoplasia.

PMID- 16424019
TI  - Differential gene expression analysis reveals generation of an autocrine loop by
      a mutant epidermal growth factor receptor in glioma cells.
AB  - The epidermal growth factor receptor (EGFR) gene is commonly amplified and
      rearranged in glioblastoma multiforme leading to overexpression of wild-type and
      mutant EGFRs. Expression of wild-type EGFR ligands, such as transforming growth
      factor-alpha (TGF-alpha) or heparin-binding EGF (HB-EGF), is also often increased
      in gliomas resulting in an autocrine loop that contributes to the growth autonomy
      of glioma cells. Glioblastoma multiformes express a characteristic EGFR mutant
      (EGFRvIII, de 2-7) that does not bind ligand, signals constitutively, and is more
      tumorigenic than the wild-type receptor. However, the downstream signals that
      mediate this increased tumorigenicity are not well understood. We hypothesized
      that signals induced specifically by EGFRvIII and not the wild-type receptor are
      more likely to mediate its increased tumorigenic activity and examined the gene
      expression profiles resulting from inducible expression of comparable levels of
      either wild-type EGFR or EGFRvIII in a U251-MG glioma cell line. Expression of
      EGFRvIII resulted in specific up-regulation of a small group of genes.
      Remarkably, all these genes, which include TGFA, HB-EGF, EPHA2, IL8, MAP4K4,
      FOSL1, EMP1, and DUSP6, influence signaling pathways known to play a key role in
      oncogenesis and function in interconnected networks. Increased expression of
      EGFRvIII-induced genes was validated by real-time PCR. The mutant receptor does
      not bind ligand, and EGFRvIII-induced expression of TGF-alpha and HB-EGF suggests
      that EGFRvIII plays a role in generating an autocrine loop using the wild-type
      EGFR in glioma. It also raises the possibility that EGFRvIII may signal, at least
      in part, through the wild-type receptor. Indeed, we show that inhibiting the
      activity of HB-EGF, a potent mitogen, with neutralizing antibodies reduces cell
      proliferation induced by expression of EGFRvIII. This suggests that the EGFRvIII
      HB-EGF-wild-type EGFR autocrine loop plays an important role in signal
      transduction by EGFRvIII in glioma cells. We also show by immunohistochemistry
      that HB-EGF expression correlates with the presence of EGFRvIII in glioblastoma
      multiforme. Thus, our study provides a new insight into oncogenic signaling by
      EGFRvIII and improves our understanding of how autocrine loops are generated in
      glioma.

PMID- 16424020
TI  - Angiostatin is directly cytotoxic to tumor cells at low extracellular pH: a
      mechanism dependent on cell surface-associated ATP synthase.
AB  - Angiostatin, a proteolytic fragment of plasminogen, is a potent angiogenesis
      inhibitor able to suppress tumor growth and metastasis through inhibition of
      endothelial cell proliferation and migration. Previously, we showed that
      angiostatin binds and inhibits F(1)F(o) ATP synthase on the endothelial cell
      surface and that anti-ATP synthase antibodies reduce endothelial cell
      proliferation. ATP synthase also occurs on the extracellular surface of a variety
      of cancer cells, where its function is as yet unknown. Here, we report that ATP
      synthase is present and active on the tumor cell surface, and angiostatin, or
      antibody directed against the catalytic beta-subunit of ATP synthase, inhibits
      the activity of the synthase. We show that tumor cell surface ATP synthase is
      more active at low extracellular pH (pH(e)). Low pH(e) is a unique characteristic
      of the tumor microenvironment. Although the mechanism of action of angiostatin
      has not been fully elucidated, angiostatin treatment in combination with acidosis
      decreases the intracellular pH (pH(i)) of endothelial cells, leading to cell
      death. We also find that, at low pH(e), angiostatin and anti-beta-subunit
      antibody induce intracellular acidification of A549 cells, as well as a direct
      cytotoxicity that is absent in tumor cells with low levels of extracellular ATP
      synthase. These results establish angiostatin as an antitumorigenic and
      antiangiogenic agent through a mechanism implicating tumor cell surface ATP
      synthase. Furthermore, these data provide evidence that extracellular ATP
      synthase plays a role in regulating pH(i) in cells challenged by acidosis.

PMID- 16424021
TI  - Increased expression of osteopontin contributes to the progression of prostate
      cancer.
AB  - Osteopontin is a secreted glycosylated phosphoprotein known to be involved in
      numerous physiologic functions and associated with the late stages of various
      cancers. We used preneoplastic and neoplastic mouse models of prostate cancer to
      determine the onset of elevated expression of osteopontin in the development of
      this disease. Osteopontin alterations occurred early in the disease with
      dysregulated expression observed in lesions of low-grade prostatic
      intraepithelial neoplasia (PIN). Over time, osteopontin expressing dysplastic
      cells seemed to increase in number in high-grade PIN and increased further in
      adenocarcinoma, and in metastasis, almost all of the cancer cells
      immunohistochemically stained positive for osteopontin overexpression. We
      examined the biological properties of human prostate cancer cell lines LNCaP and
      PC-3, in which osteopontin overexpression was achieved via lentiviral gene
      transduction. Evidence was obtained that osteopontin could contribute to a
      proliferative advantage in both cell types, although more significantly in LNCaP
      than PC-3. Osteopontin also influenced their in vitro invasive ability, and
      again, most strikingly in the weakly oncogenic LNCaP. Furthermore, excess
      osteopontin induced the LNCaP cells to acquire a strong intravasation potential
      in vivo in the chicken embryo chorioallantoic membrane assay for blood vessel
      penetration. These results establish a correlation between an increased gradient
      of osteopontin expression throughout the stages of murine prostate cancer,
      beginning from the preneoplastic lesions to distant metastases that suggests a
      proliferative and invasive advantages to those prostate tumor cells
      overexpressing osteopontin. Together, these findings support a strategy designed
      to target osteopontin in the context of prostate cancer therapy.

PMID- 16424023
TI  - Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer.
AB  - Human chromosome 1p35-p36 has long been suspected to harbor a tumor suppressor
      gene in pancreatic cancer and other tumors. We found that expression of rap1GAP,
      a gene located in this chromosomal region, is significantly down-regulated in
      pancreatic cancer. Only a small percentage of preneoplastic pancreatic
      intraductal neoplasia lesions lost rap1GAP expression, whereas loss of rap1GAP
      expression occurred in 60% of invasive pancreatic cancers, suggesting that
      rap1GAP contributes to pancreatic cancer progression. In vitro and in vivo
      studies showed that loss of rap1GAP promotes pancreatic cancer growth, survival,
      and invasion, and may function through modulation of integrin activity.
      Furthermore, we showed a high frequency of loss of heterozygosity of rap1GAP in
      pancreatic cancer. Collectively, our data identify rap1GAP as a putative tumor
      suppressor gene in pancreatic cancer.

PMID- 16424022
TI  - Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: role in
      epithelial-mesenchymal transition.
AB  - Homeobox genes encode transcription factors that control cell differentiation and
      play essential roles in developmental patterning. Increasing evidence indicates
      that many homeobox genes are aberrantly expressed in cancers, and that their
      deregulation significantly contributes to tumor progression. The homeobox gene
      HOXA10 controls uterine organogenesis during embryonic development and functional
      endometrial differentiation in the adult. We investigated whether HOXA10
      expression is deregulated in endometrial carcinomas, and how counteracting this
      aberrant expression modifies tumor behavior. We found that down-regulation of
      HOXA10 expression in endometrial carcinomas strongly correlates with increased
      tumor grade and is associated with methylation of the HOXA10 promoter. Enforced
      expression of HOXA10 in endometrial carcinoma cells inhibited invasive behavior
      in vitro and tumor dissemination in nude mice. The inhibitory effect of HOXA10 on
      invasive behavior was attributable at least in part to the ability of HOXA10 to
      induce expression of the epithelial cell adhesion molecule E-cadherin by down
      regulating expression of Snail, a repressor of E-cadherin gene transcription.
      These findings reveal a novel role for HOXA10 deregulation in the progression of
      endometrial carcinoma by promoting epithelial-mesenchymal transition.

PMID- 16424024
TI  - The P2X7 receptor sustains the growth of human neuroblastoma cells through a
      substance P-dependent mechanism.
AB  - P2X(7) is a receptor for extracellular nucleotides expressed by different normal
      cell types. P2X(7) triggering may result in stimulation of cell proliferation or
      induction of apoptosis depending on the level of activation. P2X(7) expression
      and function in B-cell chronic lymphocytic leukemia has been shown to correlate
      with disease severity. Here, we have asked the question of whether P2X(7) is
      expressed and functional in neuroblastoma, a pediatric tumor of neuroectodermal
      origin. P2X(7) was detected both in primary neuroblastoma tumors and in
      neuroblastoma cell lines. In the latter cells, P2X(7) stimulation by ATP was
      found to trigger (a) increased intracellular calcium fluxes, (b) plasma membrane
      depolarization, and (c) formation of a nonselective plasma membrane permeable
      pore. In contrast to the usual response typically observed in the majority of
      cell types, P2X(7) in vitro stimulation did not induce caspase-3 activation or
      apoptosis of neuroblastoma cells but rather supported their proliferation. Growth
      stimulation was partially due to substance P release from nucleotide-activated
      neuroblastoma cells. Therefore, neuroblastoma cells seem to have molded P2X(7)
      function to their advantage in two ways (i.e., by silencing P2X(7) proapoptotic
      activity and by coupling P2X(7) stimulation to release of locally acting trophic
      factors).

PMID- 16424025
TI  - Effect of rapamycin on mouse chronic lymphocytic leukemia and the development of
      nonhematopoietic malignancies in Emu-TCL1 transgenic mice.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the world. The
      TCL1 gene, responsible for prolymphocytic T cell leukemia, is also overexpressed
      in human B cell malignancies and overexpression of the Tcl1 protein occurs
      frequently in CLL. Aging transgenic mice that overexpress TCL1 under control of
      the mu immunoglobulin gene enhancer, develop a CD5+ B cell lymphoproliferative
      disorder mimicking human CLL and implicating TCL1 in the pathogenesis of CLL. In
      the current study, we exploited this transgenic mouse to investigate two
      different CLL-related issues: potential treatment of CLL and characterization of
      neoplasms that accompany CLL. We successfully transplanted CLL cells into
      syngeneic mice that led to CLL development in the recipient mice. This approach
      allowed us to verify the involvement of the Tcl1/Akt/mTOR biochemical pathway in
      the disease by testing the ability of a specific pharmacologic agent, rapamycin,
      to slow CLL. We also showed that 36% of these transgenic mice were affected by
      solid malignancies, in which the expression of the Tcl1 protein was absent. These
      findings indicate that other oncogenic mechanism(s) may be involved in the
      development of solid tumors in Emu-TCL1 transgenic mice.

PMID- 16424026
TI  - Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S
      proteasome pathway.
AB  - IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is
      conjugated to many cellular proteins. However, its role in protein degradation is
      unclear. Here, we show that ISG15 is highly elevated and extensively conjugated
      to cellular proteins in many tumors and tumor cell lines. The increased levels of
      ISG15 in tumor cells were found to be associated with decreased levels of
      polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15
      specific small interfering RNA (siRNA) was shown to increase the levels of
      polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in
      regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down
      regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of
      ISG15 protein conjugates, also increased the levels of polyubiquitinated
      proteins. Together, our results suggest that the ISG15 pathway, which is
      deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome
      pathway by interfering with protein polyubiquitination/degradation.

PMID- 16424027
TI  - Cisplatin mimics ARF tumor suppressor regulation of RelA (p65) nuclear factor
      kappaB transactivation.
AB  - The RelA (p65) nuclear factor-kappaB (NF-kappaB) subunit can contribute towards
      tumor cell survival through inducing the expression of a variety of antiapoptotic
      genes. However, the NF-kappaB response can show great diversity and is not always
      antiapoptotic. Here, we find that cisplatin, a DNA cross-linking agent and
      commonly used anticancer compound, does not affect RelA nuclear translocation but
      modulates its transcriptional activity. Similar to other genotoxic agents, such
      as daunorubicin and UV light, cisplatin treatment in the U-2 OS osteosarcoma cell
      line represses RelA activity and inhibits expression of the NF-kappaB
      antiapoptotic target gene Bcl-x(L). The mechanism through which cisplatin
      achieves these effects is different to daunorubicin and UV light but shows great
      similarity to the RelA regulatory pathway induced by the ARF tumor suppressor:
      cisplatin regulation of RelA requires ATR/Chk1 activity, represses Bcl-x(L) but
      not XIAP expression, and results in phosphorylation of RelA at Thr(505). In
      contrast to these results, another chemotherapeutic drug etoposide activates NF
      kappaB and induces expression of these target genes. Thus, within a single tumor
      cell line, there is great heterogeneity in the NF-kappaB response to different,
      commonly used chemotherapeutic drugs. These observations suggest that it might be
      possible to minimize the ability of RelA to inhibit cancer therapy by
      diagnostically predicting the type of chemotherapeutic drug most compatible with
      NF-kappaB functionality in a tumor cell type. Moreover, our data indicate that at
      least with respect to RelA, cisplatin functions as an ARF mimic. Other drugs
      capable of mimicking this aspect of ARF function might therefore have therapeutic
      potential.

PMID- 16424028
TI  - Efficient inhibition of intra-peritoneal tumor growth and dissemination of human
      ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal
      antibody treatment.
AB  - The L1 cell adhesion molecule is implicated in the control of proliferation,
      migration, and invasion of several tumor cell types in vitro. Recently, L1
      overexpression was found to correlate with tumor progression of ovarian
      carcinoma, one of the most common causes of cancer-related deaths in gynecologic
      malignant diseases. To evaluate L1 as a potential target for ovarian cancer
      therapy, we investigated the effects of anti-L1 monoclonal antibodies (chCE7 and
      L1-11A) on proliferation and migration of L1-positive human SKOV3ip ovarian
      carcinoma cells in vitro and the therapeutic efficacy of L1-11A against i.p.
      SKOV3ip tumor growth in nude mice. In vitro, both anti-L1 antibodies efficiently
      inhibited the proliferation of SKOV3ip cells as well as other L1-expressing tumor
      cell lines (renal carcinoma, neuroblastoma, and colon carcinoma). On two cell
      lines, hyper-cross-linking of L1-11A with a secondary antibody was necessary for
      significant inhibition of proliferation, indicating that cross-linking of L1 is
      required for the antiproliferative effect. L1-negative prostate carcinoma cells
      were not influenced by antibody treatment. Biweekly treatment of ovarian
      carcinoma-bearing mice with L1-11A led to a dose-dependent and significant
      reduction of tumor burden (up to -63.5%) and ascites formation (up to -75%). This
      effect was associated with reduced proliferation within the tumors. L1-directed
      antibody-based inhibition of peritoneal growth and dissemination of human ovarian
      carcinoma cells represents important proof-of-principle for the development of a
      new therapy against one of the leading gynecologic malignant diseases.

PMID- 16424029
TI  - Restoring E-cadherin expression increases sensitivity to epidermal growth factor
      receptor inhibitors in lung cancer cell lines.
AB  - The epidermal growth factor receptor (EGFR) is overexpressed in the majority of
      non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as
      gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E
      Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC
      prognosis and progression, and interacts with EGFR. The zinc finger
      transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting
      histone deacetylases (HDAC). We identified a significant correlation between
      sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their
      predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E
      Cadherin transfection into a gefitinib-resistant line increased its sensitivity
      to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275,
      induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic
      effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines
      including those harboring EGFR mutations. Thus, combined HDAC inhibitor and
      gefitinib treatment represents a novel pharmacologic strategy for overcoming
      resistance to EGFR inhibitors in patients with lung cancer.

PMID- 16424030
TI  - The synthetic compound CC-5079 is a potent inhibitor of tubulin polymerization
      and tumor necrosis factor-alpha production with antitumor activity.
AB  - We have found that the synthetic compound CC-5079 potently inhibits cancer cell
      growth in vitro and in vivo by a novel combination of molecular mechanisms. CC
      5079 inhibits proliferation of cancer cell lines from various organs and tissues
      at nanomolar concentrations. Its IC(50) value ranges from 4.1 to 50 nmol/L. The
      effect of CC-5079 on cell growth is associated with cell cycle arrest in G(2)-M
      phase, increased phosphorylation of G(2)-M checkpoint proteins, and apoptosis. CC
      5079 prevents polymerization of purified tubulin in a concentration-dependent
      manner in vitro and depolymerizes microtubules in cultured cancer cells. In
      competitive binding assays, CC-5079 competes with [(3)H]colchicine for binding to
      tubulin; however, it does not compete with [(3)H]paclitaxel (Taxol) or
      [(3)H]vinblastine. Our data indicate that CC-5079 inhibits cancer cell growth
      with a mechanism of action similar to that of other tubulin inhibitors. However,
      CC-5079 remains active against multidrug-resistant cancer cells unlike other
      tubulin-interacting drugs, such as Taxol and colchicine. Interestingly, CC-5079
      also inhibits tumor necrosis factor-alpha (TNF-alpha) secretion from
      lipopolysaccharide-stimulated human peripheral blood mononuclear cells (IC(50),
      270 nmol/L). This inhibitory effect on TNF-alpha production is related to its
      inhibition of phosphodiesterase type 4 enzymatic activity. Moreover, in a mouse
      xenograft model using HCT-116 human colorectal tumor cells, CC-5079 significantly
      inhibits tumor growth in vivo. In conclusion, our data indicate that CC-5079
      represents a new chemotype with novel mechanisms of action and that it has the
      potential to be developed for neoplastic and inflammatory disease therapy.

PMID- 16424032
TI  - Targeting cell-impermeable prodrug activation to tumor microenvironment
      eradicates multiple drug-resistant neoplasms.
AB  - The tumor microenvironment is notably enriched with a broad spectrum of
      proteases. The proteolytic specificities of peptide substrates provide modular
      chemical tools for the rational design of cell-impermeable prodrugs that are
      specifically activated by proteases extracellularly in the tumor
      microenvironment. Targeting cell-impermeable prodrug activation to tumor
      microenvironment will significantly reduce drug toxicity to normal tissues. The
      activated prodrug attacks both tumor and stroma cells through a "bystander
      effect" without selectively deleting target-producing cells, therefore further
      minimizing resistance and toxicity. Here, we showed that legumain, the only
      asparaginyl endopeptidase of the mammalian genome, is highly expressed by
      neoplastic, stromal, and endothelial cells in solid tumors. Legumain is present
      extracellularly in the tumor microenvironment, associated with matrix as well as
      cell surfaces and functional locally in the reduced pH of the tumor
      microenvironment. A novel legumain-activated, cell-impermeable doxorubicin
      prodrug LEG-3 was designed to be activated exclusively in the tumor
      microenvironment. Upon administration, there is a profound increase of the end
      product doxorubicin in nuclei of cells in tumors but little in other tissues.
      This tumor microenvironment-activated prodrug completely arrested growth of a
      variety of neoplasms, including multidrug-resistant tumor in vivo and
      significantly extended survival without evidence of myelosuppression or cardiac
      toxicity. The tumor microenvironment-activated prodrug design can be extended to
      other proteases and chemotherapeutic compounds and provides new potentials for
      the rational development of more effective functionally targeted cancer
      therapeutics.

PMID- 16424033
TI  - Synergistic effects of gemcitabine and gefitinib in the treatment of head and
      neck carcinoma.
AB  - Although the combination of gemcitabine and radiation produces a high frequency
      of complete responses in the treatment of locally advanced head and neck cancer,
      substantial toxicity suggests that an improvement in the therapeutic index is
      required. The purpose of this study was to determine if gefitinib could improve
      the efficacy of gemcitabine and if drug schedule is important. We hypothesized
      that gemcitabine followed by gefitinib would be superior to the opposite order
      because of both cell cycle and growth factor signaling interactions. Using UMSCC
      1 cells in vitro, we confirmed that gefitinib arrested cells in G(1) and
      suppressed phospho-epidermal growth factor receptor (p(Y845)EGFR) and that
      gemcitabine arrested cells in S phase and stimulated p(Y845)EGFR. The schedule of
      gemcitabine followed by gefitinib caused arrest of cells in S phase. Gefitinib
      suppressed gemcitabine-mediated p(Y845)EGFR stimulation. This schedule caused
      decreased p(S473)AKT, increased poly(ADP-ribose) polymerase cleavage, and
      increased apoptosis compared with gemcitabine alone. The schedule of gefitinib
      followed by gemcitabine also caused suppression of p(Y845)EGFR but arrested cells
      in G(1). This schedule in which gefitinib was used first was associated with
      stable levels of p(S473)AKT and minimal poly(ADP-ribose) polymerase cleavage and
      apoptosis. These results were reflected in experiments in nude mice bearing UMSCC
      1 xenografts, in which there was greater tumor regression and apoptosis when
      animals received gemcitabine followed by gefitinib during the first week of
      therapy. These findings suggest that the schedule of gemcitabine followed by
      gefitinib may increase the therapeutic index over gemcitabine alone and, combined
      with clinical data, encourage exploration of combination of gemcitabine, EGFR
      inhibitors, and radiation.

PMID- 16424031
TI  - Effect of adenovirus-mediated heat shock protein expression and oncolysis in
      combination with low-dose cyclophosphamide treatment on antitumor immune
      responses.
AB  - Heat shock proteins such as gp96 have the ability to chaperone peptides and
      activate antigen-presenting cells. In this study, we tested whether adenovirus
      mediated overexpression of secreted or membrane-associated forms of gp96 in tumor
      cells would stimulate an antitumor immune response. Studies were carried out in
      C57Bl/6 mice bearing aggressively growing s.c. tumors derived from syngeneic TC-1
      cells, a cell line that expresses HPV16 E6 and E7 proteins. We found that
      secreted gp96 can induce protective and therapeutic antitumor immune responses.
      Our data also indicate that the antitumor effect of sgp96 expression seems to be
      limited by the induction of suppressive regulatory T cells (Treg). TC-1 tumor
      transplantation increased the number of splenic and tumor-infiltrating Tregs.
      Importantly, treatment of mice with low-dose cyclophosphamide decreased the
      number of Tregs and enhanced the immunostimulatory effect of sgp96 expression. We
      also tested whether an oncolytic vector (Ad.IR-E1A/TRAIL), that is able to induce
      tumor cell apoptosis and, potentially, release cryptic tumor epitopes in
      immunogenic form, could stimulate antitumor immune responses. Although tumor
      cells infected ex vivo with Ad.IR-E1A/TRAIL had no antitumor effect when used as
      a vaccine alone, the additional treatment with low-dose cyclophosphamide resulted
      in the elimination of pre-established tumors. This study gives a rationale for
      testing approaches that suppress Tregs in combination with oncolytic or
      immunostimulatory vectors.

PMID- 16424034
TI  - Activity of the adenoviral E1A deletion mutant dl922-947 in ovarian cancer:
      comparison with E1A wild-type viruses, bioluminescence monitoring, and
      intraperitoneal delivery in icodextrin.
AB  - The adenoviral mutant dl922-947 has potent activity in a variety of tumors. We
      investigated the efficacy of dl922-947 in ovarian carcinoma; compared its
      activity to wild-type adenovirus, dl309, and dl1520; and investigated the use of
      icodextrin to enhance activity in vivo. We also assessed the utility of
      luciferase bioluminescence imaging to quantify the response of human ovarian
      carcinoma xenografts to dl922-947. Ovarian carcinoma cell lines were transfected
      in vitro with dl922-947, adenovirus 5 wild-type (Ad5 WT), dl309, and dl1520 and
      monitored for S-phase induction, viral protein expression, replication, and
      overall survival. In vivo, the efficacy of dl922-947 when delivered in PBS or
      icodextrin to female nude mice bearing IGROV1 xenografts was determined. In
      vitro, dl922-947 induced lysis with greater efficacy than Ad5 WT, dl309, or
      dl1520 in all ovarian carcinoma cell lines tested, which was associated with
      earlier expression of viral proteins and S-phase induction. The lytic effect in
      immortalized ovarian surface epithelial cells confirmed that cellular
      retinoblastoma pathway status is a strong determinant of dl922-947 activity. In
      vivo, i.p. delivery of dl922-947 (5 x 10(9) particles daily x 5) increased median
      survival from 20 to 96 days (P < 0.0001) and delivery in icodextrin-enhanced
      survival further. However, delayed hepatic toxicity was evident in some dl922-947
      treated mice, which was not dependent upon viral replication within tumor cells
      or the liver. dl922-947 has potency in ovarian carcinoma and i.p. delivery in
      icodextrin may enhance this activity. Immunocompetent models of ovarian carcinoma
      are required for further evaluation of hepatotoxicity.

PMID- 16424035
TI  - Oncogenic BRAF is required for tumor growth and maintenance in melanoma models.
AB  - The usual paradigm for developing kinase inhibitors in oncology is to use a high
      affinity proof-of-concept inhibitor with acceptable metabolic properties for key
      target validation experiments. This approach requires substantial medicinal
      chemistry and can be confounded by drug toxicity and off-target activities of the
      test molecule. As a better alternative, we have developed inducible short-hairpin
      RNA xenograft models to examine the in vivo efficacy of inhibiting oncogenic
      BRAF. Our results show that tumor regression resulting from BRAF suppression is
      inducible, reversible, and tightly regulated in these models. Analysis of
      regressing tumors showed the primary mechanism of action for BRAF to be increased
      tumor cell proliferation and survival. In a metastatic melanoma model,
      conditional BRAF suppression slowed systemic tumor growth as determined by in
      vivo bioluminescence imaging. Taken together, gain-of-function BRAF signaling is
      strongly associated with in vivo tumorigenicity, confirming BRAF as an important
      target for small-molecule and RNA interference-based therapeutics.

PMID- 16424036
TI  - Structure of the kinase domain of an imatinib-resistant Abl mutant in complex
      with the Aurora kinase inhibitor VX-680.
AB  - We present a high-resolution (2.0 A) crystal structure of the catalytic domain of
      a mutant form of the Abl tyrosine kinase (H396P; Abl-1a numbering) that is
      resistant to the Abl inhibitor imatinib. The structure is determined in complex
      with the small-molecule inhibitor VX-680 (Vertex Pharmaceuticals, Cambridge, MA),
      which blocks the activity of various imatinib-resistant mutant forms of Abl,
      including one (T315I) that is resistant to both imatinib and BMS-354825
      (dasatinib), a dual Src/Abl inhibitor that seems to be clinically effective
      against all other imatinib-resistant forms of BCR-Abl. VX-680 is shown to have
      significant inhibitory activity against BCR-Abl bearing the T315I mutation in
      patient-derived samples. The Abl kinase domain bound to VX-680 is not
      phosphorylated on the activation loop in the crystal structure but is
      nevertheless in an active conformation, previously unobserved for Abl and
      inconsistent with the binding of imatinib. The adoption of an active conformation
      is most likely the result of synergy between the His(396)Pro mutation, which
      destabilizes the inactive conformation required for imatinib binding, and the
      binding of VX-680, which favors the active conformation through hydrogen bonding
      and steric effects. VX-680 is bound to Abl in a mode that accommodates the
      substitution of isoleucine for threonine at residue 315 (the "gatekeeper"
      position). The avoidance of the innermost cavity of the Abl kinase domain by VX
      680 and the specific recognition of the active conformation explain the
      effectiveness of this compound against mutant forms of BCR-Abl, including those
      with mutations at the gatekeeper position.

PMID- 16424037
TI  - OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor
      tyrosine kinases with antitumor activity in mouse xenograft models.
AB  - OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase
      insert domain receptor (KDR), which is currently being evaluated in clinical
      studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact
      cells and also inhibits these targets in vivo following oral dosing. We have
      investigated the relationships between the potency observed in cell-based assays
      in vitro, the plasma exposure levels achieved following oral dosing, the time
      course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor
      xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged
      inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this
      dose range was associated with antitumor activity. Similarly, prolonged
      inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral
      doses of 100 to 200 mg/kg, which was the dose level associated with significant
      antitumor activity in this model as well as in the majority of other xenograft
      models tested. The data suggest that antitumor activity of OSI-930 in mouse
      xenograft models is observed at dose levels that maintain a significant level of
      inhibition of the molecular targets of OSI-930 for a prolonged period.
      Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930
      at these effective dose levels provides an estimate of the target plasma
      concentrations that may be required to achieve prolonged inhibition of Kit and
      KDR in humans and which would therefore be expected to yield a therapeutic
      benefit in future clinical evaluations of OSI-930.

PMID- 16424039
TI  - The penetration of anticancer drugs through tumor tissue as a function of
      cellular adhesion and packing density of tumor cells.
AB  - To reach cancer cells in optimal quantities, therapeutic agents must be delivered
      to tumors through their imperfect blood vascular system, cross vessel walls into
      the interstitium, and penetrate multiple layers of tissue. Strategies to enhance
      drug penetration have potential to improve therapeutic outcome. The development
      of multicellular layers (MCLs), in which tumor cells are grown on a semipermeable
      Teflon support membrane, has facilitated quantification of drug penetration
      through solid tissue. The goals of the present study were to quantify the
      penetration of anticancer drugs as a function of cellular adhesion and packing
      density and to determine the effects of variable penetration on therapeutic
      efficacy in this model system. We compared the properties of MCLs grown from two
      epithelioid and round subclones of a colon carcinoma cell line. One pair of
      epithelioid and round sublines differed in expression of alpha-E-catenin, and
      both pairs generated MCLs with different packing density. The penetration of
      commonly used anticancer agents (paclitaxel, doxorubicin, methotrexate, and 5
      fluorouracil) through MCLs derived from these cell lines was significantly
      greater through the round (loosely packed) than through the epithelioid (tightly
      packed) sublines. In MCLs treated with doxorubicin, we observed greater survival
      in the tightly packed cell lines than in the loosely packed cell lines. Impaired
      penetration of anticancer agents through MCLs derived from the tightly packed
      cell lines and relative resistance to killing of cells within them by doxorubicin
      treatment strengthen the role of tumor cell adhesion and packing density as
      contributing to drug resistance.

PMID- 16424038
TI  - Antitumor activity of epidermal growth factor receptor-related protein is
      mediated by inactivation of ErbB receptors and nuclear factor-kappaB in
      pancreatic cancer.
AB  - The erbB family of receptor tyrosine kinases plays critical roles in human
      cancers, including pancreatic cancer. Discovering a specific agent, which targets
      multiple members of the erbB family, would be important in pancreatic cancer
      therapy. Recently, we isolated a novel negative regulator of epidermal growth
      factor receptor (EGFR), termed EGFR-related protein (ERRP), whose expression
      attenuates EGFR activation. In the current study, we examined the effects of
      recombinant ERRP on the growth and ligand-induced activation of multiple members
      of erbB family in three pancreatic cancer cell lines that express varying levels
      of EGFR and other member(s) of its family, specifically HER-2. Additionally, we
      compared the growth inhibitory effect of ERRP with that of Erbitux or Herceptin.
      Our results showed that ERRP is most effective in inhibiting proliferation of
      BxPC-3, HPAC, and PANC-1 pancreatic cancer cells. ERRP also inhibited ligand
      induced activation of EGFR, HER-2, and HER-3 (ErbB3). In contrast, Erbitux and
      Herceptin only partially or modestly inhibited activation of EGFR, HER-2, and HER
      3. Most importantly, ERRP was found to inhibit pancreatic tumor growth in a
      severe combined immunodeficient mouse xenograft model. The antitumor activity of
      ERRP correlates well with tumor differentiation and down-regulation of nuclear
      factor-kappaB activity. In summary, our results suggest that ERRP is an effective
      pan-erbB inhibitor, which could be a potential therapeutic agent for pancreatic
      cancers expressing different levels and subclasses of erbB family of proteins.

PMID- 16424040
TI  - Farnesyl and geranylgeranyl transferase inhibitors induce G1 arrest by targeting
      the proteasome.
AB  - Isoprenoid inhibitors are being evaluated as agents for the treatment of cancer.
      Their antitumor activity is attributed to inhibition of post-translational
      modification of Ras, which is crucial for its translocation and attachment to the
      plasma membrane, and ultimate involvement in signal transduction. However,
      whether blocking of Ras is solely responsible for the observed antitumor activity
      is unresolved. In this report, we propose an alternate mechanism. Using breast
      tumor models, we show that agents possessing a lactone moiety, including statins
      (such as lovastatin) and the isoprenoid inhibitors (such as FTI-277 and GGTI
      298), mediate their cell cycle inhibitory activities by blocking the chymotrypsin
      activity of the proteasome in vitro. This results in the accumulation of cyclin
      dependent kinase inhibitors p21 and p27 with subsequent G(1) arrest. Cells devoid
      of p21 were refractory to the growth-inhibitory activity of lovastatin, FTI-277,
      and GGTI-298. However, in these p21 null cells, isoprenylation of key substrates
      of farnesyl transferase (such as Ras) and of geranylgeranyl transferase (such as
      RAP-1) were inhibited by FTI-277 and GGTI-298, respectively, suggesting that
      although both these isoprenoid inhibitors reached and inhibited their intended
      targets, inhibition of the isoprenylation of Ras and RAP-1A are not sufficient to
      mediate G(1) arrest. We also show that the cell cycle effects can be attributed
      to the functional lactone moiety of the aforementioned agents. Collectively, our
      data suggest that FTI and GGTI and other agents containing an active lactone
      moiety mediate G(1) arrest via inhibition of the proteasome and up-regulation of
      p21, independent of the inhibition of isoprenylation of Ras or RAP-1.

PMID- 16424041
TI  - Radiation-induced changes in gene expression involve recruitment of existing
      messenger RNAs to and away from polysomes.
AB  - Although ionizing radiation has been shown to influence gene transcription,
      little is known about the effects of radiation on gene translational efficiency.
      To obtain a genome-wide perspective of the effects of radiation on gene
      translation, microarray analysis was done on polysome-bound RNA isolated from
      irradiated human brain tumor cells; to allow for a comparison with the effects of
      radiation on transcription, microarray analysis was also done using total RNA.
      The number of genes whose translational activity was modified by radiation was
      approximately 10-fold greater than those whose transcription was affected. The
      radiation-induced change in a gene's translational activity was shown to involve
      the recruitment of existing mRNAs to and away from polysomes. Moreover, the
      change in a gene's translational activity after irradiation correlated with
      changes in the level of its corresponding protein. These data suggest that
      radiation modifies gene expression primarily at the level of translation. In
      contrast to transcriptional changes, there was considerable overlap in the genes
      affected at the translational level among brain tumor cell lines and normal
      astrocytes. Thus, the radiation-induced translational control of a subset of
      mRNAs seems to be a fundamental component of cellular radioresponse.

PMID- 16424042
TI  - RNA interference-mediated depletion of phosphoinositide 3-kinase activates
      forkhead box class O transcription factors and induces cell cycle arrest and
      apoptosis in breast carcinoma cells.
AB  - Breast cancer is one of the most common malignancies affecting women in the
      Western world and one in seven women is predicted to develop invasive breast
      cancer in their lifetime. Breast cancer arises following the accumulation of a
      series of somatic changes often including deregulation of key signal transduction
      pathways. The phosphoinositide 3-kinase (PI3K) pathway has been shown to be
      activated in breast cancer and overexpression of PI3K is sufficient to confer a
      malignant phenotype. Activation of the PI3K pathway serves to repress forkhead
      box class O (FoxO) transcription factor-mediated growth arrest and apoptosis. In
      this study, we used small interfering RNA (siRNA) to knockdown PI3K in three
      breast cancer cell lines representing different stages of cancer development.
      Transfection of PI3K siRNA in breast cancer cells resulted in a significant
      decrease in cell viability and induction of apoptosis irrespective of their
      estrogen receptor alpha (ERalpha) or ErbB2 status. PI3K depletion also resulted
      in a significant G(1) phase cell cycle arrest in ERalpha-positive breast cancer
      cells. Further, our data showed that PI3K knockdown resulted in a significant
      activation of FoxO; interestingly, a simultaneous knockdown of FoxO1a rescued the
      cells from apoptosis. Furthermore, the downstream effects of FoxO activation were
      found to be inhibition of cyclin-dependent kinase 4, cyclin-dependent kinase 6,
      and cyclin D1, and accumulation of p27/Kip1. Thus, we suggest that (a) PI3K plays
      a critical role in breast cancer development and (b) gene therapeutic approaches
      aimed at PI3K or the pharmacologic inhibitors of PI3K could be developed for the
      management of breast cancer.

PMID- 16424043
TI  - Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear
      antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these
      complexes.
AB  - Rapamycin and its derivatives are promising anticancer agents, but the exact
      mechanisms by which these drugs induce cell cycle arrest and inhibit tumor growth
      are unknown. A biochemical analysis of human mammary tumor cell lines indicated
      that rapamycin-induced antiproliferative effects correlated with down-regulation
      of cellular p21 levels and the levels of p21 in cyclin-dependent kinase (Cdk) 2
      and 4 complexes. Cyclin D1 overexpression reversed rapamycin action and this
      reversal correlated with increased levels of cellular p21, higher levels of p21
      associated with Cdk2, and stabilization of cyclin D1/Cdk2/p21/proliferating cell
      nuclear antigen (PCNA) complexes. Experiments using a novel cyclin D1-Cdk2 fusion
      protein or a kinase-dead mutant of the fusion protein indicated that reversal of
      rapamycin action required not only the formation of complexes with p21 and PCNA
      but also complex-associated kinase activity. Similar results were observed in
      vivo. The rapamycin derivative RAD001 (everolimus) inhibited the growth of mouse
      mammary tumors, which correlated with the disruption of cyclin D1/Cdk2 complexes.
      The potential implications of these results with respect to the use of rapamycin
      derivatives in breast cancer therapy are discussed.

PMID- 16424044
TI  - Intracellular signaling pathways involved in the cell growth inhibition of glioma
      cells by melatonin.
AB  - Melatonin is an indolamine mostly produced in the pineal gland, soluble in water,
      and highly lipophilic, which allows it to readily cross the blood-brain barrier.
      Melatonin possesses antioxidant properties and its long-term administration in
      rodents has not been found to cause noteworthy side effects. In the present work,
      we found that millimolar concentrations of this indolamine reduced cell growth of
      C6 glioma cells by 70% after 72 hours of treatment, inhibiting cell progression
      from G(1) to S phase of the cell cycle. Intraperitoneal administration of 15
      mg/kg body weight of melatonin to rats previously injected in the flank with C6
      glioma cells reduces tumor growth by 50% 2 weeks after the implant. Inhibition of
      cell growth does not depend on melatonin membrane receptor activation whereas it
      seemingly relates to the reduction of intracellular basal free radical levels by
      30%. Increase of basal redox state of the cells and constitutive activation of
      tyrosine kinase receptor [receptor tyrosine kinase (RTK)] pathways, including the
      extracellular signal-regulated kinase 1/2 (ERK1/2) and the Akt and protein kinase
      C (PKC) signaling pathways, contribute to the progression of the gliomas leading
      to the constitutive activation of the redox-dependent survival transcription
      factor nuclear factor kappaB (NF-kappaB). The antioxidant effect of melatonin in
      C6 cells is associated to inhibition of NF-kappaB and Akt, but not of ERK1/2. The
      antiproliferative effect of the indolamine on these cells is partially abolished
      when coincubated with the PKC activator 12-O-tetradecanoylphorbol-13-acetate,
      thus indicating that the ability of melatonin to change cellular redox state may
      be inactivating the pathway RTK/PKC/Akt/NF-kappaB.

PMID- 16424045
TI  - 17-allylamino-17-demethoxygeldanamycin synergistically potentiates tumor necrosis
      factor-induced lung cancer cell death by blocking the nuclear factor-kappaB
      pathway.
AB  - Nuclear factor-kappaB (NF-kappaB), a survival signal induced by tumor necrosis
      factor (TNF), contributes substantially to the resistance to TNF-induced cell
      death. Previous studies suggest that heat shock protein 90 (Hsp90) regulates the
      stability and function of receptor-interaction proteins (RIP) and IkappaB kinase
      beta (IKKbeta), the key components of the TNF-induced NF-kappaB activation
      pathway. In this study, we showed that the Hsp90 inhibitor 17-allylamino-17
      demethoxygeldanamycin (17AAG) was synergistic with TNF to induce apoptotic cell
      death in a panel of lung tumor-derived cell lines. Treatment with 17AAG caused
      degradation of RIP and IKKbeta that, in turn, blocked TNF-induced NF-kappaB
      activation and antiapoptotic gene expression. The synergistic cytotoxicity was
      detected only when TNF treatment followed 17AAG preexposure. Importantly, the
      potentiation of cell death was abolished in NF-kappaB-disabled cells that express
      a nondegradable IkappaBalpha mutant (IkappaBalphaAA). These results suggest that
      the cytotoxicity seen with 17AAG and TNF treatment results from blocking TNF
      induced NF-kappaB activation. The other components of the TNF receptor I
      signaling cascade were not altered, whereas TNF-induced c-Jun NH(2)-terminal
      kinase activation and apoptosis were potentiated. A similar synergism for
      inducing apoptosis was also observed in 17AAG-treated and TNF-related apoptosis
      inducing ligand (TRAIL)-treated cancer cells. Our results suggest that NF-kappaB
      plays a key role in the resistance of lung cancer cells to TNF and TRAIL and that
      disabling this survival signal with 17AAG followed by TNF or TRAIL treatment
      could be an effective new therapeutic strategy for lung cancer.

PMID- 16424046
TI  - Selective targeting of antitumor immune responses with engineered live-attenuated
      Listeria monocytogenes.
AB  - Improved immunization and ex vivo T-cell culture strategies can generate larger
      numbers and more potent tumor-specific effector cells than previously possible.
      Nonetheless, the capacity of these cells to eliminate established tumors is
      limited by their ability to efficiently enter tumor-bearing organs and mediate
      their effector function. In the current study, we show that the administration of
      an engineered organ-homing microbe selectively targets tumor-specific immune
      responses to metastases within that organ. Specifically, an attenuated Listeria
      monocytogenes strain, which preferentially infects the liver following systemic
      administration, dramatically enhances the activity of a cancer vaccine against
      liver metastases but not metastases in the lung. This enhanced activity results
      from both local recruitment of innate immune effectors as well as concentration
      and increased activation of vaccine-induced antitumor T cells within the liver.
      These findings show a general approach to focus systemic cancer immunotherapies
      to specific organs bearing tumor metastases by taking advantage of differential
      tropisms and the proinflammatory nature of microbes.

PMID- 16424047
TI  - De novo induction of a cancer/testis antigen by 5-aza-2'-deoxycytidine augments
      adoptive immunotherapy in a murine tumor model.
AB  - Recent studies suggest that immunotherapy targeting specific tumor-associated
      antigens (TAAs) may be beneficial in cancer patients. However, most of these TAAs
      are tumor type specific and heterogeneous among patients, thus limiting their
      applications. Here, we describe the de novo induction of a cancer/testis antigen
      (CTA) for immunotherapy of tumors of various histologies. The murine CTA P1A,
      normally expressed only in a few tumor lines, could be induced de novo in all P1A
      negative cancer lines of eight histologic origins in vitro and in various murine
      xenografts by systemic administration of 5-aza-2'-deoxycytidine. The induction of
      P1A expression correlated strongly with demethylation of the CpG island in the
      promoter region of this gene. The induced antigen was processed and presented
      properly for recognition by H-2L(d)-restricted P1A-specific CTLs. The combination
      of a demethylating agent and adoptive transfer of P1A-specific CTL effectively
      treated lung metastases in syngeneic mice challenged with P1A-negative 4T1
      mammary carcinoma cells. These data show a novel strategy of combined
      chemoimmunotherapy of cancer targeting a CTA induced de novo in a broad range of
      tumor histologies, and support further evaluation of chromatin-remodeling agents
      for human cancer therapy.

PMID- 16424048
TI  - Prostaglandin E2 impairs CD4+ T cell activation by inhibition of lck:
      implications in Hodgkin's lymphoma.
AB  - Many tumors, including Hodgkin's lymphoma, are associated with decreased cellular
      immunity and elevated levels of prostaglandin E(2) (PGE(2)), a known inhibitor of
      CD4+ T cell activation, suggested to be involved in immune deviation in cancer.
      To address the molecular mechanisms tumor-derived PGE(2) might have on primary
      human CD4+ T cells, we used a whole genome-based transcriptional approach and
      show that PGE(2) severely limited changes of gene expression induced by signaling
      through the T cell receptor and CD28. This data suggests an interference of
      PGE(2) at an early step of T cell receptor signaling: indeed, PGE(2) stimulation
      of T cells leads to inactivation of lck and reduced phosphorylation of ZAP70.
      Antiapoptotic genes escaped PGE(2)-induced inhibition resulting in partial
      protection from apoptosis in response to irradiation or Fas-mediated signaling.
      As a functional consequence, PGE(2)-treated CD4+ T cells are arrested in the cell
      cycle associated with up-regulation of the cyclin/cyclin-dependent kinase
      inhibitor p27(kip1). Most importantly, CD4+ T cells in Hodgkin's lymphoma show
      similar regulation of genes that were altered in vitro by PGE(2) in T cells from
      healthy individuals. These data strongly suggest that PGE(2) is an important
      factor leading to CD4+ T cell impairment observed in Hodgkin's lymphoma.

PMID- 16424049
TI  - Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor
      induced T regulatory cells and T-cell anergy in tumor-bearing host.
AB  - The accumulation of myeloid suppressor cells (MSCs) is associated with immune
      suppression in tumor-bearing mice and in cancer patients. The suppressive
      activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115
      (macrophage colony-stimulating factor receptor), and F4/80. Gr-1(+)CD115(+) MSCs,
      in addition to being able to suppress T-cell proliferation in vitro, can induce
      the development of Foxp3(+) T regulatory cells (Treg) in vivo, which are anergic
      and suppressive. Furthermore, the secretion of interleukin (IL)-10 and
      transforming growth factor-beta by Gr-1(+)CD115(+) MSCs was induced and enhanced,
      respectively, on IFN-gamma stimulation. The development of Treg requires antigen
      associated activation of tumor-specific T cells, depends on the presence of IFN
      gamma and IL-10, and is independent of the nitric oxide-mediated suppressive
      mechanism by MSC. Our data provide evidence that Gr-1(+)CD115(+) MSC can mediate
      the development of Treg in tumor-bearing mice and show a novel immune suppressive
      mechanism by which MSCs can suppress antitumor responses.

PMID- 16424050
TI  - The in vivo expansion rate of properly stimulated transferred CD8+ T cells
      exceeds that of an aggressively growing mouse tumor.
AB  - It has been hypothesized that rapidly dividing tumor cells can outpace adoptively
      transferred antitumor lymphocytes when tumors are large. However, this hypothesis
      is at odds with clinical observations indicating that bulky tumors can be
      destroyed by small numbers of adoptively transferred antitumor T cells. We sought
      to measure the relative growth rates of T cells and tumor cells in a model using
      transgenic CD8(+) T cells specific for the gp100(25-33) H-2D(b) epitope (called
      pmel-1) to treat large, well-established s.c. B16 melanoma. We tested the effect
      of the immunization using an altered peptide ligand vaccine alone or in
      combination with interleukin-2 (IL-2) by analyzing the kinetics of T-cell
      expansion using direct enumeration. We found that pmel-1 T cells proliferated
      explosively during a 5-day period following transfer. Calculations from net
      changes in population suggest that, at the peak of cell division, pmel-1 T cells
      divide at a rate of 5.3 hours per cell division, which was much faster than B16
      tumor cells during optimal growth (24.9 hours per cell division). These results
      clearly indicate that the notion of a kinetic "race" between the tumor and the
      lymphocyte is no contest when adoptively transferred cells are stimulated with
      immunization and IL-2. When appropriately stimulated, tumor-reactive T-cell
      expansion can far exceed the growth of even an aggressively growing mouse tumor.

PMID- 16424051
TI  - Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can
      activate and enhance tumor-specific T-cell responses.
AB  - Radiofrequency thermal ablation (RFA) destroys tumoral tissue generating a local
      necrosis followed by marked inflammatory response with a dense T-cell infiltrate.
      In this study, we tested whether hepatocellular carcinoma thermal ablation can
      induce or enhance T-cell responses specific for hepatocellular carcinoma
      associated antigens. Peripheral blood mononuclear cells derived from 20 patients
      with hepatocellular carcinoma were stimulated before and a month after RFA
      treatment with autologous hepatocellular carcinoma-derived protein lysates
      obtained before and immediately after RFA treatment. The effect of thermal
      ablation on memory T-cell responses to recall antigens [tetanus toxoid, protein
      purified derivative (PPD), Escherichia coli] was also assessed. T-cell reactivity
      was analyzed in an IFN-gamma enzyme-linked immunospot assay and by intracellular
      IFN-gamma staining. Treatment was followed by a significant increase of patients
      responsive either to tumor antigens derived from both the untreated
      hepatocellular carcinoma tissue (P < 0.05) and the necrotic tumor (P < 0.01) and
      by a higher frequency of circulating tumor-specific T cells. T-cell responses to
      recall antigens were also significantly augmented. Phenotypic analysis of
      circulating T and natural killer cells showed an increased expression of
      activation and cytotoxic surface markers. However, tumor-specific T-cell
      responses were not associated with protection from hepatocellular carcinoma
      relapse. Evidence of tumor immune escape was provided in one patient by the
      evidence that a new nodule of hepatocellular carcinoma recurrence was not
      recognized by T cells obtained at the time of RFA. In conclusion, RFA treatment
      generates the local conditions for activating the tumor-specific T-cell response.
      Although this effect is not sufficient for controlling hepatocellular carcinoma,
      it may represent the basis for the development of an adjuvant immunotherapy in
      patients undergoing RFA for primary and secondary liver tumors.

PMID- 16424052
TI  - Tumor cells transduced with the MHC class II Transactivator and CD80 activate
      tumor-specific CD4+ T cells whether or not they are silenced for invariant chain.
AB  - The specificity and potency of the immune system make immunotherapy a potential
      strategy for the treatment of cancer. To exploit this potential, we have
      developed cell-based cancer vaccines consisting of tumor cells expressing
      syngeneic MHC class II and costimulatory molecules. The vaccines mediate tumor
      regression in mice and activate human CD4+ T cells in vitro. Previous vaccines
      were generated by transducing MHC II negative tumor cells with a single HLA-DR
      allele. Because expression of multiple MHC II alleles would facilitate
      presentation of a broader repertoire of tumor antigens, we have now transduced
      tumor cells with the MHC class II transactivator (CIITA), a regulatory gene that
      coordinately increases expression of all MHC II alleles. Previous studies in mice
      indicated that coexpression of the MHC II accessory molecule invariant chain (Ii)
      inhibited presentation of endogenously synthesized tumor antigens and reduced
      vaccine efficacy. To determine if Ii expression affects presentation of MHC class
      II-restricted endogenously synthesized tumor antigens in human tumor cells, HLA
      DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory
      molecule gene, and with or without small interfering RNAs (siRNA) specific for
      Ii. Ii expression is silenced >95% in CIITA/CD80/siRNA transductants; down
      regulation of Ii does not affect HLA-DR expression or stability; and Ii(+) and
      Ii(-) transductants activate human CD4+ T cells to DRB1*0701-restricted HER-2/neu
      epitopes. Therefore, tumor cells transduced with the CIITA, CD80, and with or
      without Ii siRNA present endogenously synthesized tumor antigens and are
      potential vaccines for activating tumor-specific CD4+ T cells.

PMID- 16424053
TI  - Efficient induction of tumor antigen-specific CD8+ memory T cells by recombinant
      lentivectors.
AB  - The success of active cancer immunotherapy entails a robust induction of tumor
      reactive effector and memory CD8+ T cells. We compared the in vivo immunogenicity
      of the melanoma-associated antigen Melan-A(26-35) encoded by third-generation
      recombinant lentivector (rec. lv) or as peptide admixed with a strong adjuvant.
      Ex vivo analyses of immunized HLA-A2/H-2K(b) mice showed that rec. lv triggered a
      stronger anti-Melan-A CD8+ T -cell response than peptide vaccine. Importantly,
      the majority of anti-Melan-A T cells elicited by rec. lv expressed the memory
      marker CD127 at the peak of the primary response. In those mice, memory T cells
      were detectable several months after priming and could be activated by recall
      peptide vaccination. These results show that immunization with rec. lv induces
      not only a strong antigen-specific CD8+ T -cell response but also a long-lasting
      T-cell memory against a bona fide tumor-associated antigen.

PMID- 16424054
TI  - Chaperoning function of stress protein grp170, a member of the hsp70 superfamily,
      is responsible for its immunoadjuvant activity.
AB  - When used as vaccines, tumor-derived stress proteins can elicit antitumor immune
      responses. For members of the hsp70 superfamily, like grp170, this seems to be
      due to (a) the chaperoning of antigenic peptide by the stress protein and (b) the
      binding of the stress protein to receptor(s) on antigen-presenting cells (APC)
      and subsequent antigen presentation. This suggests that domains exist on the
      stress protein for each function. In this study, we determine the ability of
      grp170 and its structural domains to (a) bind to and present melanoma-associated
      antigen gp100 to the immune system and (b) to bind to receptors on APCs. A direct
      correlation between chaperone function, binding to APCs in a receptor-like
      manner, and antitumor immunity was observed. Two mutants that share no common
      sequence, yet are both effective in their antitumor activities, compete with one
      another for APC binding. Studies of other members of the hsp70 superfamily,
      hsp110 and hsp70, or their domain deletion mutants, further confirmed that APC
      binding segregates with chaperoning function and not sequence. Therefore, these
      studies suggest that molecular chaperoning is involved in stress protein
      interactions with APCs, antigen binding, and in eliciting antitumor immunity,
      thus bridging this ancient function of stress proteins in prokaryotes to their
      ability to elicit immunity in higher organisms.

PMID- 16424055
TI  - Vaccine with beta-defensin 2-transduced leukemic cells activates innate and
      adaptive immunity to elicit potent antileukemia responses.
AB  - Murine beta-defensin 2 (MBD2) is a small antimicrobial peptide of the innate
      immune system. Recent study showed that MBD2 could not only recruit immature
      dendritic cells but also activate them by Toll-like receptor 4 and thus may
      provide a critical link between the innate immune system and the adaptive immune
      response. In this report, we examined the antileukemia activity of MBD2 in a
      murine model of acute lymphoid leukemia (ALL) L1210. L1210 cells were engineered
      to secrete biologically functional MBD2. MBD2-modified L1210 (L1210-MBD2) showed
      significantly reduced leukemogenecity, resulting in a 80% rate of complete
      leukemia rejection. Inoculation of mice with L1210-MBD2 induced enhanced CTL and
      natural killer (NK) activity and augmented interleukin-12 and IFN-gamma
      production. All the recovered mice from the inoculation showed a protective
      immunity to the following challenge with parental L1210 cells and generate
      leukemia-specific memory CTL. Vaccines with irradiated L1210-MBD2 cells could
      cure 50% leukemia-bearing mice. Depletion of CD8+ T cells but not CD4+ T cells
      completely abrogated the antileukemia activity of MBD2. Interestingly, NK cells
      were also required for the MBD2-mediated antileukemia response, although ALL
      generally display a high degree of resistance to NK-mediated lysis. Our results
      suggest that MBD2 can activate both innate and adaptive immunity to generate
      potent antileukemia response, and MBD2 immunotherapy warrants further evaluation
      as a potential treatment for ALL.

PMID- 16424056
TI  - Polymorphisms in RET and its coreceptors and ligands as genetic modifiers of
      multiple endocrine neoplasia type 2A.
AB  - Germ line missense mutations in the RET proto-oncogene are responsible for the
      inherited cancer syndrome multiple endocrine neoplasia type 2A (MEN2A). The
      clinical presentation of the disease and the age at onset varies even within
      families, where patients carry the same mutation. These variations in phenotypes
      suggest a role for genetic modifiers, and recently, it has been reported that
      polymorphisms within RET (G691S/S904S) may have such a modifier effect on the age
      at onset. Here, we investigate whether this observed association could be
      confirmed in a larger set of 384 individuals from MEN2 families from four
      different European populations. In addition, we tested as modifiers four other
      single nucleotide polymorphisms (SNPs), which we have found in a previous
      association study of RET, its coreceptors, and ligands to be associated with the
      risk of developing sporadic medullary thyroid carcinoma. We could not replicate
      the association between G691S/S904S and modifier effects in MEN2A families in any
      of the four European families analyzed. Of the other SNPs tested, only RET A432A
      showed a positive weak effect on tumor spectrum within MEN2A, which requires
      replication in a larger series.

PMID- 16424058
TI  - Expression of a fibroblast growth factor-binding protein during the development
      of adenocarcinoma of the pancreas and colon.
AB  - The activity of growth factors is crucial for tumor progression. We previously
      characterized a secreted fibroblast growth factor-binding protein (FGF-BP1) as a
      chaperone molecule, which enhances the biological functions of FGFs by releasing
      FGFs from the extracellular matrix. Here, we characterize the frequency and
      pattern of FGF-BP1 expression during the malignant progression of pancreas and
      colorectal carcinoma. For this, we generated monoclonal antibodies that detect
      FGF-BP1 protein in formalin-fixed, paraffin-embedded tissues and applied in situ
      hybridization to detect FGF-BP1 mRNA in adjacent tissue sections. FGF-BP1 protein
      and mRNA were found up-regulated (>70% positive) in parallel (r = 0.70, P <
      0.0001) in colon adenoma (n = 9) as well as primary (n = 46) and metastatic (n =
      71) colorectal cancers relative to normal colon epithelia (all P < 0.0001, versus
      normal). Similarly, pancreatitis (n = 17), pancreatic intraepithelial neoplasia
      (n = 80), and pancreatic adenocarcinoma (n = 67) showed a significant up
      regulation of FGF-BP1 compared with normal pancreas (n = 42; all P < 0.0001,
      relative to normal). Furthermore, the biological activity of FGF-BP1 is
      neutralized by one of the antibodies, suggesting the potential for antibody-based
      therapeutic targeting. We propose that the up-regulation of the secreted FGF-BP1
      protein during initiation of pancreas and colon neoplasia could make this protein
      a possible serum marker indicating the presence of high-risk premalignant
      lesions.

PMID- 16424059
TI  - Induction of metastasis by S100P in a rat mammary model and its association with
      poor survival of breast cancer patients.
AB  - S100P, an EF-hand calcium-binding protein, has been reported to be associated
      with the progression of many types of cancers. Transfection of an expression
      vector for S100P into a benign, nonmetastatic rat mammary cell line causes a 4-
      to 6-fold increase in its level in all four transformant cell clones. When the
      resultant transformant cell lines are introduced in turn into the mammary fat
      pads of syngeneic Furth-Wistar rats, there is a significant 3-fold increase in
      local muscle invasion and a significant induction of metastasis in 64% to 75% of
      tumor-bearing animals. In a group of 303 breast cancer patients followed for up
      to 20 years, antibodies to S100P immunocytochemically stain 161 primary tumors.
      Survival of patients with S100P-positive carcinomas is significantly worse by
      about 7-fold than for those with negatively stained carcinomas. There is also a
      significant association between the class level of immunocytochemical staining of
      the carcinoma cells and decreased patient survival. Positive staining for S100P
      is significantly associated with that for two other metastasis-inducing proteins,
      S100A4 and osteopontin. Patients with tumors that stained positively for both
      S100P and S100A4 have a significantly reduced survival of 1.1% over patients with
      either S100 protein alone. Multivariate regression analysis identifies S100P,
      S100A4, and osteopontin as the most significant independent indicators of death
      in this group of patients. These results suggest that stratification of patients
      into groups according to expression of multiple metastasis-inducing proteins may
      lead to a more accurate prediction of patient survival.

PMID- 16424057
TI  - Diagnostic markers of ovarian cancer by high-throughput antigen cloning and
      detection on arrays.
AB  - A noninvasive screening test would significantly facilitate early detection of
      epithelial ovarian cancer. This study used a combination of high-throughput
      selection and array-based serologic detection of many antigens indicative of the
      presence of cancer, thereby using the immune system as a biosensor. This high
      throughput selection involved biopanning of an ovarian cancer phage display
      library using serum immunoglobulins from an ovarian cancer patient as bait.
      Protein macroarrays containing 480 of these selected antigen clones revealed 65
      clones that interacted with immunoglobulins in sera from 32 ovarian cancer
      patients but not with sera from 25 healthy women or 14 patients having other
      benign or malignant gynecologic diseases. Sequence analysis data of these 65
      clones revealed 62 different antigens. Among the markers, we identified some
      known antigens, including RCAS1, signal recognition protein-19, AHNAK-related
      sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1
      (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic
      initiation factor 5A, and casein kinase II, as well as many previously
      uncharacterized antigenic gene products. Using these 65 antigens on protein
      microarrays, we trained neural networks on two-color fluorescent detection of
      serum IgG binding and found an average sensitivity and specificity of 55% and
      98%, respectively. In addition, the top 6 of the most specific clones resulted in
      an average sensitivity and specificity of 32% and 94%, respectively. This global
      approach to antigenic profiling, epitomics, has applications to cancer and
      autoimmune diseases for diagnostic and therapeutic studies. Further work with
      larger panels of antigens should provide a comprehensive set of markers with
      sufficient sensitivity and specificity suitable for clinical testing in high-risk
      populations.

PMID- 16424060
TI  - DNA methylation alterations in the pancreatic juice of patients with suspected
      pancreatic disease.
AB  - Molecular markers of pancreatic neoplasia could aid in the evaluation of visible
      pancreatic lesions and indicate neoplasia invisible to imaging. We evaluated
      methylation-specific PCR (MSP) assays that detect aberrantly methylated DNA for
      their use as markers of pancreatic neoplasia. Methylation analysis was done on
      pancreatic juice collected endoscopically or surgically from 155 individuals with
      suspected pancreatic disease: 56 patients had pancreatic ductal adenocarcinoma,
      17 had intraductal papillary mucinous neoplasms, 26 had symptomatic chronic
      pancreatitis, 12 controls lacked evidence of pancreatic disease, and 44 were
      asymptomatic individuals at increased risk of developing familial pancreatic
      cancer undergoing screening for pancreatic neoplasia. Pancreatic juice DNA was
      analyzed for promoter methylation using conventional MSP assays for 17 genes. For
      six genes, pancreatic juice methylation was quantified using real-time
      quantitative MSP (QMSP; Cyclin D2, FOXE1, NPTX2, ppENK, p16, and TFPI2).
      Quantifying pancreatic juice methylation using QMSP with a cutoff of >1%
      methylated DNA could better predict pancreatic cancer than detecting methylation
      using conventional MSP. In the endoscopic group, 9 of 11 patients with pancreatic
      cancer, but none of 64 individuals without neoplasia had > or =1% methylation for
      two or more of the best five QMSP assays (82% sensitivity and 100% specificity; P
      < 0.0001). The prevalence of pancreatic juice methylation in patients with
      chronic pancreatitis was less than in patients with pancreatic cancer but higher
      than in controls and similar to high-risk individuals. The detection and
      quantification of aberrantly methylated DNA in pancreatic juice is a promising
      approach to the diagnosis of pancreatic cancer.

PMID- 16424061
TI  - Age-related changes of the cervix influence human papillomavirus type
      distribution.
AB  - Approximately 15 human papillomavirus (HPV) types cause virtually all cervical
      cancer whereas other HPV types are unrelated to cancer. We were interested in
      whether some noncarcinogenic types differ from carcinogenic in their affinity for
      the cervical transformation zone, where nearly all HPV-induced cancers occur. To
      examine this possibility, we tested cervical specimens from 8,374 women without
      cervical precancer and cancer participating in a population-based study in
      Guanacaste for >40 HPV types using PCR. We compared age-group specific
      prevalences of HPV types of the alpha9 species, which are mainly carcinogenic and
      include HPV16, to the genetically distinct types of the alpha3/alpha15 species
      (e.g., HPV71), which are noncarcinogenic and common in vaginal specimens from
      hysterectomized women. We related HPV detection of each group to the location of
      the junction between the squamous epithelium of the ectocervix and vagina and the
      columnar epithelium of the endocervical canal. Models evaluated the independent
      effects of amount of exposed columnar epithelium (ectopy) and age on the presence
      of alpha9 or alpha3/alpha15 types. Prevalence of alpha9 types (7.6%) peaked in
      the youngest women, declined in middle-aged women, and then increased slightly in
      older women. By contrast, prevalence of alpha3/alpha15 types (7.6%) tended to
      remain invariant or to increase with increasing age. Detection of alpha9
      infections increased (P(trend) < 0.0005) but alpha3/alpha15 infections decreased
      (P(trend) < 0.0005) with increasing exposure of the columnar epithelia. Older age
      and decreasing cervical ectopy were independently positively associated with
      having an alpha3/alpha15 infection compared with having an alpha9 infection.
      These patterns need to be confirmed in other studies and populations. We suggest
      that these genetically distinct groups of HPV types may differ in tissue
      preferences, which may contribute to their differences in carcinogenic potential.

PMID- 16424062
TI  - Tagging single-nucleotide polymorphisms in antioxidant defense enzymes and
      susceptibility to breast cancer.
AB  - It is generally believed that the initiation of breast cancer is a consequence of
      cumulative genetic damage leading to genetic alterations and provoking
      uncontrolled cellular proliferation and/or aberrant programmed cell death, or
      apoptosis. Reactive oxygen species have been related to the etiology of cancer as
      they are known to be mitogenic and therefore capable of tumor promotion. The aim
      of this study was to assess the role of common variation in 10 polymorphic genes
      coding for antioxidant defense enzymes in modulating individual susceptibility to
      breast cancer using a case-control study (N cases = 4,474 and N controls =
      4,580). Both cases and controls were from the East Anglian region of the United
      Kingdom. We have identified a set of 54 single nucleotide polymorphisms (SNPs)
      that efficiently tag all the known SNPs in the 10 genes and are also expected to
      tag any unknown SNPs in each gene. We found no evidence for association of common
      variants in SOD1, SOD2, GPX1, GPX4, GSR, TXNRD1, and TXN2. There was borderline
      evidence for association of variants in CAT g27168a {P [2 degrees of freedom
      (df)] = 0.05}, TXN t2715c [P (2 df) = 0.007], and TXNRD2 A66S and TXNRD2 g23524a
      (P(trend) = 0.074 and 0.046, respectively). For TXNRD2 A66S [AS versus AA: odds
      ratio (OR), 1.05; 95% confidence intervals (95% CI), 0.96-1.15; SS versus AA: OR,
      1.12; 95% CI, 0.98-1.29], there are bioinformatics data to suggest that it is
      functional but confirmation in independent data sets is required before they can
      be regarded as definitive breast cancer susceptibility alleles. Even if
      confirmed, these four alleles would account for just 0.32% of the excess familial
      risk of breast cancer.

PMID- 16424063
TI  - Chemoprevention of human prostate cancer by oral administration of green tea
      catechins in volunteers with high-grade prostate intraepithelial neoplasia: a
      preliminary report from a one-year proof-of-principle study.
AB  - Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in
      several experimental models. Recent studies showed that 30% of men with high
      grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer
      (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of
      principle clinical trial to assess the safety and efficacy of GTCs for the
      chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs
      preparations were assessed by high-performance liquid chromatography [(-)
      epigallocathechin, 5.5%; (-)-epicatechin, 12.24%; (-)-epigallocatechin-3-gallate,
      51.88%; (-)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, <1%].
      Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to
      sign an informed consent form and were enrolled in this double-blind, placebo
      controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each
      (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs
      treated men (incidence, approximately 3%), whereas nine cancers were found among
      the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did
      not change significantly between the two arms, but GTCs-treated men showed values
      constantly lower with respect to placebo-treated ones. International Prostate
      Symptom Score and quality of life scores of GTCs-treated men with coexistent
      benign prostate hyperplasia improved, reaching statistical significance in the
      case of International Prostate Symptom Scores. No significant side effects or
      adverse effects were documented. To our knowledge, this is the first study
      showing that GTCs are safe and very effective for treating premalignant lesions
      before CaP develops. As a secondary observation, administration of GTCs also
      reduced lower urinary tract symptoms, suggesting that these compounds might also
      be of help for treating the symptoms of benign prostate hyperplasia.

PMID- 16424064
TI  - Dietary soy isoflavones inhibit estrogen effects in the postmenopausal breast.
AB  - Soy isoflavones are promising dietary agents for prevention of breast cancer.
      Isoflavones bind estrogen receptors (ER) and may variably act as either estrogen
      agonists or antagonists depending on the estrogen environment. In this study, we
      used a postmenopausal primate model to evaluate interactive effects of dietary
      soy isoflavones and estrogen on risk markers for breast cancer. The experiment
      followed a randomized factorial design in which 31 ovariectomized adult female
      cynomolgus monkeys were divided into social groups of three to four animals each
      and rotated through eight different diets containing the human equivalent of 0,
      60, 120, or 240 mg/d soy isoflavones with a dose of oral micronized 17beta
      estradiol (E(2)) corresponding to either a low (0.09 mg/d) or a high (0.5 mg/d)
      postmenopausal estrogen environment. Treatment periods lasted 4 months with a 1
      month washout period between diets. The highest isoflavone dose resulted in
      significantly lower breast proliferation and uterine size in the high-estrogen
      environment. These effects were accompanied by divergent changes in breast
      markers of ER activation in which pS2 expression was significantly lower and
      progesterone receptor expression was significantly higher following the 240 mg
      isoflavone dose. All isoflavone doses resulted in lower serum estrone and E(2)
      concentrations in the high-estrogen environment. In contrast, isoflavone
      treatment had no significant estrogen agonist effects and minimal antagonistic
      effects in the lower-estrogen environment. These findings show that in the
      presence of estrogen higher doses of dietary soy isoflavones may alter ER
      signaling and induce selective antagonistic effects in the breast.

PMID- 16424066
TI  - Enhanced mitochondrial sensitivity to creatine in rats bred for high aerobic
      capacity.
AB  - Qualitative and quantitative measures of mitochondrial function were performed in
      rats selectively bred 15 generations for intrinsic aerobic high running capacity
      (HCR; n = 8) or low running capacity (LCR; n=8). As estimated from a speed-ramped
      treadmill exercise test to exhaustion (15 degrees slope; initial velocity of 10
      m/min, increased 1 m/min every 2 min), HCR rats ran 10 times further (2,375+/-80
      m) compared with LCR rats (238+/-12 m). Fiber bundles were obtained from the
      soleus and chemically permeabilized. Respiration was measured 1) in the absence
      of ADP, 2) in the presence of a submaximally stimulating concentration of ADP
      (0.1 mM ADP, with and without 20 mM creatine), and 3) in the presence of a
      maximally stimulating concentration of ADP (2 mM). Although non-ADP-stimulated
      and maximally ADP-stimulated rates of respiration were 13% higher in HCR compared
      with LCR, the difference was not statistically significant (P>0.05). Despite a
      similar rate of respiration in the presence of 0.1 mM ADP, HCR rats demonstrated
      a higher rate of respiration in the presence of 0.1 mM ADP+20 mM creatine (HCR
      33% higher vs. LCR, P<0.05). Thus mitochondria from HCR rats exhibit enhanced
      mitochondrial sensitivity to creatine (i.e., the ability of creatine to decrease
      the Km for ADP). We propose that increased respiratory sensitivity to ADP in the
      presence of creatine can effectively increase muscle sensitivity to ADP during
      exercise (when creatine is increased) and may be, in part, a contributing factor
      for the increased running capacity in HCR rats.

PMID- 16424065
TI  - Post-traumatic stress disorder in patients with cardiac disease: predicting
      vulnerability from emotional responses during admission for acute coronary
      syndromes.
AB  - OBJECTIVES: To assess frequency and predictors of post-traumatic stress disorder
      (PTSD), measured by the Post Traumatic Stress-self report version, at three
      months after admission for acute coronary syndromes (ACS). DESIGN: Two-phase
      prospective study. SETTING: Four coronary care units. PATIENTS: 135 patients
      admitted to hospital with ACS confirmed by ECG and cardiac enzyme changes.
      RESULTS: 20 patients (14.8%) showed a symptom pattern characteristic of PTSD at
      three months assessed by a conservative scoring criterion. Severity of chest pain
      and psychological factors during admission were predictive of PTSD severity.
      Acute stress symptoms, depression, negative affect, hostility, and pain scores
      were independent predictors of three-month PTSD symptoms (R(2) = 0.495, p <
      0.001). In contrast, demographic factors (age, sex, education level and income)
      were unrelated to post-traumatic symptoms, as were markers of clinical disease
      severity. CONCLUSIONS: Patient vulnerability to PTSD three months after ACS is
      predictable on the basis of psychological state and chest pain at the time of
      admission. This may be valuable to the clinician, as PTSD after myocardial
      infarction is associated with poorer quality of life, reduced adherence to drug
      treatment and increased likelihood of cardiovascular morbidity.

PMID- 16424067
TI  - FDG-PET imaging of pulmonary inflammation in healthy volunteers after airway
      instillation of endotoxin.
AB  - Recent studies indicate that a focal, limited, inflammatory response can be
      safely elicited after direct bronchial instillation of small doses of endotoxin
      into a single lung segment. Because the radiotracer [18F]fluorodeoxyglucose
      ([18F]FDG) is taken up at accelerated rates within inflamed tissues, we
      hypothesized that we could detect and quantify this regional inflammatory
      response with positron emission tomography (PET). We imaged 18 normal volunteers
      in a dose-escalation study with 3 endotoxin dosing groups (n = 6 in each group):
      1 ng/kg, 2 ng/kg, and 4 ng/kg. Endotoxin was instilled by bronchoscopy into a
      segment of the right middle lobe, with imaging performed approximately 24 h
      later, followed by bronchoalveolar lavage (BAL). A "subtraction imaging analysis"
      was performed in the highest dose cohort to identify the area of inflammation,
      using the preendotoxin scan as a baseline. BAL neutrophil counts were
      significantly higher in the highest dose group compared with the other two groups
      (1,413 +/- 625 vs. 511 +/- 396 and 395 +/- 400 cells/mm3; P < 0.05).
      Autoradiography performed on cells harvested by BAL showed specific
      [3H]deoxyglucose ([3H]DG) uptake limited to neutrophils. In vitro [3H]DG uptake
      in BAL neutrophils in the 4 ng/kg dose group (but not in the 2 ng/kg group) was
      statistically greater than in peripheral blood neutrophils obtained before
      endotoxin instillation. The rate of [18F]FDG uptake was greatest in the 4 ng/kg
      group, with a consistent, statistically significant increase in the rate of
      uptake after endotoxin instillation compared with baseline. We conclude that the
      inflammatory response to low-dose endotoxin in a single lung segment can be
      visualized and quantified by imaging with FDG-PET.

PMID- 16424068
TI  - Exercise-induced abdominal muscle fatigue in healthy humans.
AB  - The abdominal muscles have been shown to fatigue in response to voluntary
      isocapnic hyperpnea using direct nerve stimulation techniques. We investigated
      whether the abdominal muscles fatigue in response to dynamic lower limb exercise
      using such techniques. Eleven male subjects [peak oxygen uptake (VO2 peak) = 50.0
      +/- 1.9 (SE) ml.kg(-1).min(-1)] cycled at >90% VO2 peak to exhaustion (14.2 +/-
      4.2 min). Abdominal muscle function was assessed before and up to 30 min after
      exercise by measuring the changes in gastric pressure (Pga) after the nerve roots
      supplying the abdominal muscles were magnetically stimulated at 1-25 Hz.
      Immediately after exercise there was a decrease in Pga at all stimulation
      frequencies (mean -25 +/- 4%; P < 0.001) that persisted up to 30 min postexercise
      (-12 +/- 4%; P = 0.001). These reductions were unlikely due to changes in
      membrane excitability because amplitude, duration, and area of the rectus
      abdominis M wave were unaffected. Declines in the Pga response to maximal
      voluntary expiratory efforts occurred after exercise (158 +/- 13 before vs. 145
      +/- 10 cmH2O after exercise; P = 0.005). Voluntary activation, assessed using
      twitch interpolation, did not change (67 +/- 6 before vs. 64 +/- 2% after
      exercise; P = 0.20), and electromyographic activity of the rectus abdominis and
      external oblique increased during these volitional maneuvers. These data provide
      new evidence that the abdominal muscles fatigue after sustained, high-intensity
      exercise and that the fatigue is primarily due to peripheral mechanisms.

PMID- 16424069
TI  - Salvage of focal cerebral ischemic damage by transfusion of high O2-affinity
      recombinant hemoglobin polymers in mouse.
AB  - Cell-free hemoglobin solutions with high oxygen affinity might be beneficial for
      selectively delivering oxygen to ischemic tissue. A recombinant hybrid hemoglobin
      molecule was designed using the human alpha-subunit and the bovine beta-subunit,
      with placement of surface cysteines to permit disulfide bond polymerization of
      the tetramers. The resulting protein generated from an Escherichia coli
      expression system had a molecular mass >1 MDa, a P50 of approximately 3 Torr, and
      a cooperativity of n = 1.0. Anesthetized mice were transfused during 2-h
      occlusion of the middle cerebral artery. Compared with transfusion with 5%
      albumin, cerebral infarct volume was reduced by 41% with transfusion of a 3%
      solution of the high oxygen-affinity hemoglobin polymer and by 50% with
      transfusion of a 6% solution of the polymer. Transfusion of a 6% solution of a
      500-kDa polymer possessing a P50 of 17 Torr and a cooperativity of n = 2.0
      resulted in a 66% reduction of infarct volume. These results indicate that cell
      free Hb polymers with P50 values much lower than that of red blood cell
      hemoglobin are highly capable of salvaging ischemic brain. The assumption that
      the P50 of blood substitutes should be similar to that of blood might not be
      warranted when used during ischemic conditions.

PMID- 16424070
TI  - Experimental determination of net protein charge, [A]tot, and Ka of nonvolatile
      buffers in bird plasma.
AB  - The quantitative mechanistic acid-base approach to clinical assessment of acid
      base status requires species-specific values for [A]tot (the total concentration
      of nonvolatile buffers in plasma) and Ka (the effective dissociation constant for
      weak acids in plasma). The aim of this study was to determine [A]tot and Ka
      values for plasma in domestic pigeons. Plasma from 12 healthy commercial domestic
      pigeons was tonometered with 20% CO2 at 37 degrees C. Plasma pH, Pco2, and plasma
      concentrations of strong cations (Na, K, Ca), strong anions (Cl, L-lactate), and
      nonvolatile buffer ions (total protein, albumin, phosphate) were measured over a
      pH range of 6.8-7.7. Strong ion difference (SID) (SID5=Na+K+Ca-Cl-lactate) was
      used to calculate [A]tot and Ka from the measured pH and Pco2 and SID5. Mean (+/
      SD) values for bird plasma were as follows: [A]tot=7.76+/-2.15 mmol/l (equivalent
      to 0.32 mmol/g of total protein, 0.51 mmol/g of albumin, 0.23 mmol/g of total
      solids); Ka=2.15+/-1.15x10(-7); and pKa=6.67. The net protein charge at normal pH
      (7.43) was estimated to be 6 meq/l; this value indicates that pigeon plasma has a
      much lower anion gap value than mammals after adjusting for high mean L-lactate
      concentrations induced by restraint during blood sampling. This finding indicates
      that plasma proteins in pigeons have a much lower net anion charge than mammalian
      plasma protein. An incidental finding was that total protein concentration
      measured by a multianalyzer system was consistently lower than the value for
      total solids measured by refractometer.

PMID- 16424071
TI  - Central excitability does not limit postfatigue voluntary activation of
      quadriceps femoris.
AB  - After fatigue, motor evoked potentials (MEP) elicited by transcranial magnetic
      stimulation and cervicomedullary evoked potentials elicited by stimulation of the
      corticospinal tract are depressed. These reductions in corticomotor excitability
      and corticospinal transmission are accompanied by voluntary activation failure,
      but this may not reflect a causal relationship. Our purpose was to determine
      whether a decline in central excitability contributes to central fatigue. We
      hypothesized that, if central excitability limits voluntary activation, then a
      caffeine-induced increase in central excitability should offset voluntary
      activation failure. In this repeated-measures study, eight men each attended two
      sessions. Baseline measures of knee extension torque, maximal voluntary
      activation, peripheral transmission, contractile properties, and central
      excitability were made before administration of caffeine (6 mg/kg) or placebo.
      The amplitude of vastus lateralis MEPs elicited during minimal muscle activation
      provided a measure of central excitability. After a 1-h rest, baseline measures
      were repeated before, during, and after a fatigue protocol that ended when
      maximal voluntary torque declined by 35% (Tlim). Increased prefatigue MEP
      amplitude (P=0.055) and cortically evoked twitch (P<0.05) in the caffeine trial
      indicate that the drug increased central excitability. In the caffeine trial,
      increased MEP amplitude was correlated with time to task failure (r=0.74,
      P<0.05). Caffeine potentiated the MEP early in the fatigue protocol (P<0.05) and
      offset the 40% decline in placebo MEP (P<0.05) at Tlim. However, this was not
      associated with enhanced maximal voluntary activation during fatigue or recovery,
      demonstrating that voluntary activation is not limited by central excitability.

PMID- 16424072
TI  - Soleus aponeurosis strain distribution following chronic unloading in humans: an
      in vivo MR phase-contrast study.
AB  - The in vivo strain properties of human skeletal muscle-tendon complexes are
      poorly understood, particularly following chronic periods of reduced load
      bearing. We studied eight healthy volunteers who underwent 4 wk of unilateral
      lower limb suspension (ULLS) to induce chronic unloading. Before and after the
      ULLS, maximum isometric ankle plantar flexion torque was determined by using a
      magnetic resonance (MR)-compatible dynamometry. Volumes of the triceps surae
      muscles and strain distribution of the soleus aponeurosis and the Achilles tendon
      at a constant submaximal plantar flexion (20% pre-maximal voluntary contraction)
      were measured by using MRI and velocity-encoded, phase-contrast MRI techniques.
      Following ULLS, volumes of the soleus and the medial gastrocnemius and the
      maximum isometric ankle plantar flexion (maximum voluntary contraction) decreased
      by 5.5+/-1.9, 7.5+/-2.7, and 48.1+/-6.1%, respectively. The strain of the
      aponeurosis along the length of the muscle before the ULLS was 0.3+/-0.3%,
      ranging from -1.5 to 2.7% in different locations of the aponeurosis. Following
      ULLS, the mean strain was -6.4+/-0.3%, ranging from -1.6 to 1.3%. The strain
      distribution of the midregion of the aponeurosis was significantly influenced by
      the ULLS, whereas the more distal component showed no consistent changes.
      Achilles tendon strain was not affected by the ULLS. These results raise the
      issue as to whether these changes in strain distribution affect the functional
      properties of the triceps surae and whether the probability of strain injuries
      within the triceps surae increases following chronic unloading in those regions
      of this muscle complex in which unusual strains occur.

PMID- 16424073
TI  - Relation between muscle fiber conduction velocity and fiber size in neuromuscular
      disorders.
AB  - To determine the relation between muscle fiber conduction velocity (MFCV) and
      muscle fiber diameter (MFD) in pathological conditions, we correlated invasively
      measured MFCV values with MFD data obtained from muscle needle biopsies in 96
      patients with various neuromuscular disorders. MFCV was significantly correlated
      with MFD and independent of the underlying disorder. Pathological diameter
      changes were fiber-type dependent, with corresponding MFCVs. A linear equation
      expresses the relation well: MFCV (m/s)=0.043.MFD (microm)+0.83. We conclude that
      fiber diameter determines MFCV largely independent of the underlying
      neuromuscular disorders studied.

PMID- 16424074
TI  - Nitric oxide in B6 mouse and nitric oxide-sensitive soluble guanylate cyclase in
      cat modulate acetylcholine release in pontine reticular formation.
AB  - ACh regulates arousal, and the present study was designed to provide insight into
      the neurochemical mechanisms modulating ACh release in the pontine reticular
      formation. Nitric oxide (NO)-releasing beads microinjected into the pontine
      reticular formation of C57BL/6J (B6) mice significantly (P < 0.0001) increased
      ACh release. Microdialysis delivery of the NO donor N-ethyl-2-(1-ethyl-2-hydroxy
      2-nitrosohydrazino)-ethanamine (NOC-12) to the mouse pontine reticular formation
      also caused a concentration-dependent increase in ACh release (P < 0.001). These
      are the first neurochemical data showing that ACh release in the pontine
      reticular formation of the B6 mouse is modulated by NO. The signal transduction
      cascade through which NO modulates ACh release in the pontine reticular formation
      has not previously been characterized. Therefore, an additional series of studies
      quantified the effects of a soluble guanylate cyclase (sGC) inhibitor, 1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), on ACh release in the cat medial
      pontine reticular formation. During naturally occurring states of sleep and
      wakefulness, but not anesthesia, ODQ caused a significant (P < 0.001) decrease in
      ACh release. These results show for the first time that NO modulates ACh in the
      medial pontine reticular formation of the cat via an NO-sensitive sGC signal
      transduction cascade. Isoflurane and halothane anesthesia have been shown to
      decrease ACh release in the medial pontine reticular formation. The finding that
      ODQ did not alter ACh release during isoflurane or halothane anesthesia
      demonstrates that these anesthetics disrupt the NO-sensitive sGC-cGMP pathway.
      Considered together, results from the mouse and cat indicate that NO modulates
      ACh release in arousal-promoting regions of the pontine reticular formation via
      an NO-sensitive sGC-cGMP pathway.

PMID- 16424075
TI  - Cerebral autoregulation is preserved during orthostatic stress superimposed with
      systemic hypotension.
AB  - We sought to determine whether cerebral autoregulation (CA) is compromised during
      orthostatic stress superimposed with systemic hypotension. Transient systemic
      hypotension was produced by deflation of thigh cuffs previously inflated to
      suprasystolic pressure, combined with or without lower body negative pressure
      (LBNP). Cardiac output (CO) decreased from a baseline of 5.0+/-0.5 l/min by 
      8.3+/-1.7, -19.2+/-2.0, and -30.6+/-3.4% during LBNP of -15, -30, and -50 Torr,
      respectively. Mean arterial pressure (MAP) was maintained during LBNP, despite
      decreases in systolic and pulse pressures. Middle cerebral arterial blood flow
      velocity (VMCA) decreased significantly from a baseline of 64+/-3 to 58+/-4 cm/s
      (-9.7+/-2.4%) at -50 Torr of LBNP. The reduction in VMCA was associated with a
      decrease in regional cerebral O2 saturation. However, the percent decrease in
      VMCA was markedly less than that of CO. This suggests that the magnitude of the
      change in VMCA (an index of cerebral blood flow) is less than would be predicted,
      given the decrease in CO. Transient systemic hypotension decreased MAP by -21+/
      2, -24+/-2, -28+/-3, and -26+/-3% at rest and during LBNP of -15, -30, and -50
      Torr, respectively. Likewise, this acute hypotension resulted in decreases in
      VMCA of -20+/-2, -21+/-2, -24+/-25, and -19+/-2% and regional cerebral O2
      saturation of -5+/-1, -6+/-1, -6+/-1, and -7+/-2% at rest and during LBNP of -15,
      -30, and -50 Torr, respectively. Complete recovery of VMCA to baseline values
      following transient hypotension (ranging from 5 to 8 s) occurred significantly
      earlier compared with MAP (from 10 to 12 s). No subjects experienced syncope
      during acute hypotension. We conclude that CA is preserved during LBNP,
      superimposed with transient systemic hypotension, despite the decrease in VMCA
      associated with sustained central hypovolemia in normal healthy individuals. This
      preserved CA is vital for the prevention of orthostatic syncope.

PMID- 16424076
TI  - Carbohydrate metabolism during prolonged exercise and recovery: interactions
      between pyruvate dehydrogenase, fatty acids, and amino acids.
AB  - During prolonged exercise, carbohydrate oxidation may result from decreased
      pyruvate production and increased fatty acid supply and ultimately lead to
      reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the
      amino acids alanine, glutamine, and glutamate, whereby the decline in pyruvate
      production could affect tricarboxycylic acid cycle flux as well as
      gluconeogenesis. To enhance our understanding of these interactions, we studied
      the time course of changes in substrate utilization in six men who cycled at 44+/
      1% peak oxygen consumption (mean+/-SE) until exhaustion (exhaustion at 3 h 23
      min+/-11 min). Femoral arterial and venous blood, blood flow measurements, and
      muscle samples were obtained hourly during exercise and recovery (3 h).
      Carbohydrate oxidation peaked at 30 min of exercise and subsequently decreased
      for the remainder of the exercise bout (P<0.05). PDH activity peaked at 2 h of
      exercise, whereas pyruvate production peaked at 1 h of exercise and was reduced
      (approximately 30%) thereafter, suggesting that pyruvate availability primarily
      accounted for reduced carbohydrate oxidation. Increased free fatty acid uptake
      (P<0.05) was also associated with decreasing PDH activity (P<0.05) and increased
      PDH kinase 4 mRNA (P<0.05) during exercise and recovery. At 1 h of exercise,
      pyruvate production was greatest and was closely linked to glutamate, which was
      the predominant amino acid taken up during exercise and recovery. Alanine and
      glutamine were also associated with pyruvate metabolism, and they comprised
      approximately 68% of total amino-acid release during exercise and recovery. Thus
      reduced pyruvate production was primarily associated with reduced carbohydrate
      oxidation, whereas the greatest production of pyruvate was related to glutamate,
      glutamine, and alanine metabolism in early exercise.

PMID- 16424077
TI  - The contribution of TWIK-related acid-sensitive K+-containing channels to the
      function of dorsal lateral geniculate thalamocortical relay neurons.
AB  - A genetic knockout was used to determine the specific contribution of TWIK
      related acid-sensitive K+ (TASK)-1 channels to the function of dorsal lateral
      geniculate nucleus (DLG) thalamocortical relay (TC) neurons. Disruption of TASK-1
      function produced an approximately 19% decrease in amplitude of the standing
      outward current (ISO) and a 3 +/- 1-mV depolarizing shift in resting membrane
      potential (Vrest) of DLG neurons. We estimated that current through TASK-1
      homodimers or TASK-1/TASK-3 heterodimers contribute(s) approximately one third of
      the current sensitive to TASK channel modulators in DLG TC neurons. The effects
      of the TASK channel blocker bupivacaine (20 microM), of muscarine (50 microM),
      and of H+ on ISO were reduced to approximately 60%, 59%, and shifted to more
      acidic pH values, respectively. The blocking effect of anandamide on ISO [30
      microM; 23 +/- 3% current decrease in wild type (WT)] was absent in TASK-1
      knockout (TASK-1-/-) mice (9 +/- 6% current increase). Comparable results were
      obtained with the more stable anand-amide derivative methanandamide (20 microM;
      20 +/- 2% decrease in WT; 4 +/- 6% increase in TASK-1-/-). Current-clamp
      recordings revealed a muscarine-induced shift in TC neuron activity from burst to
      tonic firing in both mouse genotypes. Electrocorticograms and sleep/wake times
      were unchanged in TASK-1-/- mice. In conclusion, our findings demonstrate a
      significant contribution of TASK-1 channels to ISO in DLG TC neurons, although
      the genetic knockout of TASK-1 did not produce severe deficits in the
      thalamocortical system.

PMID- 16424078
TI  - Pseudolarix acid B, a new tubulin-binding agent, inhibits angiogenesis by
      interacting with a novel binding site on tubulin.
AB  - Tubulin-binding agents have received considerable interest as potential tumor
      selective angiogenesis-targeting drugs. Herein, we report that pseudolarix acid B
      (PAB), isolated from the traditional Chinese medicinal plant Pseudolarix
      kaempferi Gordon, is a tubulin-binding agent. We further demonstrate that PAB
      significantly and dose-dependently inhibits proliferation, migration, and tube
      formation by human microvessel enthothelial cells. It is noteworthy that PAB
      eliminated newly formed endothelial tubes and microvessels both in vitro and in
      vivo. In addition, PAB dramatically arrested the cell cycle at G2/M phase. PAB
      also induced endothelial cell retraction, intercellular gap formation, and
      promoted actin stress fiber formation in conjunction with disruption of the
      tubulin and actin cytoskeletons. All of these effects occurred at noncytotoxic
      concentrations of PAB. We found that these effects of PAB are attributable to
      depolymerization of tubulin by direct interaction with a distinct binding site on
      tubulin compared with those of colchicine and vinblastine. Taken together, these
      findings show that PAB is a candidate antiangiogenic agent for use in cancer
      therapy, and they provide proof of principle for targeting this novel binding
      site on tubulin as a new strategy for treating cancer.

PMID- 16424079
TI  - Insulin secretion is controlled by mGlu5 metabotropic glutamate receptors.
AB  - Recent evidence suggests that metabotropic glutamate (mGlu) receptors are
      involved in the regulation of hormone secretion in the endocrine pancreas. We
      report here that endogenous activation of mGlu5 receptors is required for an
      optimal insulin response to glucose both in clonal beta-cells and in mice. In
      clonal beta-cells, mGlu5 receptors were expressed at the cell surface and were
      also found in purified insulin-containing granules. These cells did not respond
      to a battery of mGlu5 receptor agonists that act extracellularly, but instead
      responded to a cell-permeant analog of glutamate with an increase in [Ca2+]i and
      insulin secretion. Both effects were largely attenuated by the mGlu5 receptor
      antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP). MPEP and its structural
      analog, (E)-2-methyl-6-styryl-pyridine (SIB-1893), reduced the increase in
      [Ca2+]i and insulin secretion induced by glucose in clonal beta-cells, whereas a
      mGlu1 receptor antagonist was inactive. mGlu5 knockout mice showed a defective
      insulin response at all times after a glucose pulse (1.5 g/kg, i.p.), whereas
      wild-type mice treated with MPEP (10 mg/kg, i.p.) showed a selective impairment
      in the late phase of insulin secretion in response to glucose challenge. Mice
      injected with MPEP or lacking mGlu5 receptors also showed a blunted glucagon
      response to an insulin challenge. We conclude that insulin secretion is under the
      control of mGlu5 receptors both in clonal beta-cells and in vivo. Drugs that
      modulate the function of mGlu5 receptors might affect glucose homeostasis by
      altering the secretion of pancreatic hormones.

PMID- 16424080
TI  - Persistence of a behavioral food-anticipatory circadian rhythm following
      dorsomedial hypothalamic ablation in rats.
AB  - Circadian rhythms of behavior in rodents are regulated by a system of circadian
      oscillators, including a master light-entrainable pacemaker in the
      suprachiasmatic nucleus that mediates synchrony to the day-night cycle, and food
      entrainable oscillators located elsewhere that generate rhythms of food
      anticipatory activity (FAA) synchronized to daily feeding schedules. Despite
      progress in elucidating neural and molecular mechanisms of circadian oscillators,
      localization of food-entrainable oscillators driving FAA remains an enduring
      problem. Recent evidence suggests that the dorsomedial hypothalamic nucleus (DMH)
      may function as a final common output for behavioral rhythms and may be critical
      for the expression of FAA (Gooley JJ, Schomer A, and Saper CB. Nat Neurosci 9:
      398-407, 2006). To determine whether the reported loss of FAA by DMH lesions is
      specific to one behavioral measure or generalizes to other measures, rats
      received large radiofrequency lesions aimed at the DMH and were recorded in cages
      with movement sensors. Total and partial DMH ablation was associated with a
      significant attenuation of light-dark-entrained activity rhythms during ad
      libitum food access, because of a selective reduction in nocturnal activity. When
      food was restricted to a single 3-h daily meal in the middle of the lights-on
      period, all DMH and intact rats exhibited significant FAA. The rhythm of FAA
      persisted during a 48-h food deprivation test and reappeared during a 72-h
      deprivation test after ad libitum food access. The DMH is not the site of
      oscillators or entrainment pathways necessary for all manifestations of FAA, but
      may participate on the output side of this circadian function.

PMID- 16424081
TI  - Direct and indirect effects of leptin on preadipocyte proliferation and
      differentiation.
AB  - Leptin has been shown to reduce body fat in vivo. Adipocytes express the leptin
      receptor; therefore, it is realistic to expect a direct effect of leptin on
      adipocyte growth and metabolism. In vitro studies examining the effect of leptin
      on adipocyte metabolism require supraphysiological doses of the protein to see a
      decrease in lipogenesis or stimulation of lipolysis, implying an indirect action
      of leptin. It also is possible that leptin reduces adipose mass by inhibiting
      preadipocyte proliferation (increase in cell number) and/or differentiation
      (lipid filling). Thus we determined direct and indirect effects of leptin on
      preadipocyte proliferation and differentiation in vitro. We tested the effect of
      leptin (0-500 ng/ml), serum from leptin-infused rats (0.25% by volume), and
      adipose tissue-conditioned medium from leptin-infused rats (0-30% by volume) on
      preadipocyte proliferation and differentiation in a primary culture of cells from
      male Sprague-Dawley rat adipose tissue. Leptin (50 ng/ml) stimulated
      proliferation of preadipocytes (P<0.05), but 250 and 500 ng leptin/ml inhibited
      proliferation of both preadipocyte and stromal vascular cell fractions (P<0.01),
      as measured by [3H]thymidine incorporation. Serum from leptin-infused rats
      inhibited proliferation of the adipose and stromal vascular fractions (P=0.01),
      but adipose tissue-conditioned medium had no effect on proliferation of either
      cell fraction. None of the treatments changed preadipocyte differentiation as
      measured by sn-glycerophosphate dehydrogenase activity. These results suggest
      that leptin could inhibit preadipocyte proliferation by modifying release of a
      factor from tissue other than adipose tissue.

PMID- 16424082
TI  - Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar
      increases in food intake and patterns of hypothalamic gene expression.
AB  - The gut peptide ghrelin has been shown to stimulate food intake after both
      peripheral and central administration, and the hypothalamic arcuate nucleus has
      been proposed to be the major site for mediating this feeding stimulatory action.
      Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin
      administration has been shown to potently stimulate feeding, suggesting that
      there may be other sites for ghrelin action. In the present study, we have
      further assessed potential sites for ghrelin action by comparing the ability of
      lateral and fourth ventricular ghrelin administration to stimulate food intake
      and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2
      nmol) in the lateral or fourth ventricle significantly increased food intake in
      the first 4 h after injection, with no ventricle-dependent differences in degree
      or time course of hyperphagia. One nanomole of ghrelin into either the lateral or
      fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y
      mRNA expression. Expression levels of agouti-related peptide or
      proopiomelanocortin mRNA were not affected by ghrelin administration. These data
      demonstrate that ghrelin can affect food intake and hypothalamic gene expression
      through interactions at multiple brain sites.

PMID- 16424083
TI  - Oxytocin actions within the supraoptic and paraventricular nuclei: differential
      effects on peripheral and intranuclear vasopressin release.
AB  - In response to forced swimming (FS), AVP is released somato-dendritically within
      the supraoptic nucleus (SON) and paraventricular nucleus (PVN), but not from
      neurohypophyseal terminals into blood. Together with AVP, oxytocin (OXT) is
      released within the SON and PVN. Here, we studied the role of intra-SON and intra
      PVN OXT in the regulation of local AVP release and into the blood in male rats.
      Within the SON, bilateral retrodialysis of an OXT receptor antagonist (OXT-A)
      increased local AVP release in response to FS [60 s, 21 degrees C, vehicle
      twofold, not significant (ns); OXT-A: 15-fold increase, P < 0.05] without
      significantly affecting basal AVP release. In addition, local OXT-A elevated
      plasma AVP secretion under basal conditions (twofold increase, P < 0.05) without
      further elevation after FS. Within the PVN, exposure to FS elevated local AVP
      release, reaching significance only in the OXT-A group (vehicle: 1.4-fold, ns;
      OXT-A: 1.6-fold increase, P = 0.050). Bilateral OXT-A into the PVN did not affect
      peripheral AVP secretion either under basal or stress conditions. Basal ACTH
      concentrations tended to be elevated by local OXT-A within the PVN (1.7-fold
      increase, P = 0.076). In contrast, the swim-induced ACTH secretion was attenuated
      after retrodialysis of OXT-A within both the SON (at 5 min) and PVN (at 15 min)
      (P < 0.05 both) compared with vehicle. The results demonstrate a receptor
      mediated effect of OXT within the SON and PVN on local and neurohypophyseal AVP
      release, which depends upon the activity conditions. Further, while exerting an
      inhibitory effect on hypothalamo-pituitary-adrenal axis activity under basal
      conditions, hypothalamic OXT is essential for an adequate acute ACTH response.

PMID- 16424084
TI  - Measurement of activation energy and oxidative phosphorylation onset kinetics in
      isolated muscle fibers in the absence of cross-bridge cycling.
AB  - This study utilized N-benzyl-p-toluene sulfonamide (BTS), a potent inhibitor of
      cross-bridge cycling, to measure 1) the relative metabolic costs of cross-bridge
      cycling and activation energy during contraction, and 2) oxygen uptake kinetics
      in the presence and absence of myosin ATPase activity, in isolated Xenopus laevis
      muscle fibers. Isometric tension development and either cytosolic Ca2+
      concentration ([Ca2+]c) or intracellular Po2 (PiO2) were measured during
      contractions at 20 degrees C in control conditions (Con) and after exposure to
      12.5 microM BTS. BTS attenuated tension development to 5+/-0.4% of Con but did
      not affect either resting or peak [Ca2+]c during repeated isometric contractions.
      To determine the relative metabolic cost of cross-bridge cycling, we measured the
      fall in PiO2) (DeltaPiO2; a proxy for Vo2) during contractions in Con and BTS
      groups. BTS attenuated DeltaP(iO2) by 55+/-6%, reflecting the relative ATP cost
      of cross-bridge cycling. Thus, extrapolating DeltaPiO2 to a value that would
      occur at 0% tension suggests that actomyosin ATP requirement is approximately 58%
      of overall ATP consumption during isometric contractions in mixed fiber types.
      BTS also slowed the fall in PiO2) (time to 63% of overall DeltaPiO2) from 75+/-9
      s (Con) to 101+/-9 s (BTS) (P<0.05), suggesting an important role of the products
      of ATP hydrolysis in determining the Vo2 onset kinetics. These results
      demonstrate in isolated skeletal muscle fibers that 1) activation energy accounts
      for a substantial proportion (approximately 42%) of total ATP cost during
      isometric contractions, and 2) despite unchanged [Ca2+]c transients, a reduced
      rate of ATP consumption results in slower Vo2 onset kinetics.

PMID- 16424085
TI  - Expression of slow myosin heavy chain during muscle regeneration is not always
      dependent on muscle innervation and calcineurin phosphatase activity.
AB  - In the literature, there is an ambiguity as to the respective roles played by
      calcineurin phosphatase activity (CPA) and muscle innervation in the
      reestablishment of the slow-twitch muscle phenotype after muscle regeneration in
      different species. In this study, we wanted to determine the role of calcineurin
      and muscle innervation on the appearance and maintenance of the slow phenotype
      during mouse muscle regeneration. The pattern of myosin expression and CPA was
      analyzed in adult (n=15), regenerating (n=45) and denervated-regenerating (n=32)
      slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles.
      Moreover, in a second group of denervated-regenerating mice (n=9), the animals
      were treated with a calcineurin inhibitor. Regeneration was induced by injection
      of cardiotoxin and in the denervated-regenerating group, denervation was carried
      out by cutting the sciatic nerve before the administration of cardiotoxin. In
      innervated-regenerating soleus muscle, CPA increased continuously after 10 days
      postinjury and by 21 days, there was a 3.5-fold increase in CPA compared with
      adult basal level, whereas in innervated-regenerating EDL muscle, CPA remained
      unchanged. Moreover, our results show that in denervated-regenerating muscles,
      the MyHC profile was identical in spite of the functional differences inherent in
      these muscles. In long-term denervated-regenerating muscles, a slow muscle
      phenotype was reexpressed both in the presence or absence of calcineurin
      inhibitor. Our results show that although in innervated-regenerating mouse
      muscle, the appearance of a slow phenotype is correlated with a peak of CPA, in
      denervated-regenerating muscles, a slow phenotype is triggered and maintained in
      a calcineurin- and nerve-independent manner.

PMID- 16424086
TI  - Macrophages and skeletal muscle regeneration: a clodronate-containing liposome
      depletion study.
AB  - The study evaluates the influence of monocytes/macrophages in the mechanisms of
      skeletal muscle injury using a mouse model and selective depletion of peripheral
      monocyte with systemic injections of liposomal clodronate (dichloromethylene
      bisphosphonate). This pharmacological treatment has been demonstrated to induce
      specific apoptotic death in monocytes and phagocytic macrophages. In the current
      studies, the liposomal clodronate injections resulted in a marked attenuation of
      the peak inflammatory response in the freeze-injured muscle in the first three
      days after injury. The effect was accompanied by a transient reduction (at day 1
      or 3 postinjury) of the expression of several genes coding for inflammatory, as
      well as growth-related mediators, including TNF, monocyte chemoattractant protein
      (MCP)-1, thioredoxin, high-mobility group AT-hook 1, insulin-like growth factor
      binding protein (IGFBP), and IGF-1. In contrast, the expression of major myogenic
      factors (i.e., MyoD and myogenin) directly involved in the
      activation/proliferation and differentiation of muscle precursor cells was not
      altered by the clodronate liposome treatment. The repair process in the injured
      muscle of clodronate liposome-treated mice was characterized by prolonged
      clearance of necrotic myofibers and a tendency for increased muscle fat
      accumulation at day 9 and 14 postinjury, respectively. In conclusion, a
      significant reduction of the initial monocyte/macrophage influx into the injured
      muscle is associated with not improved, but moderately impaired, repair processes
      after skeletal muscle injury.

PMID- 16424087
TI  - Ankyrin repeat and SOCS box protein 15 regulates protein synthesis in skeletal
      muscle.
AB  - Ankyrin repeat and SOCS box protein 15 (ASB15) is an Asb family member expressed
      predominantly in skeletal muscle. We have previously reported that ASB15 mRNA
      abundance decreases after administration of beta-adrenergic receptor agonists.
      Because beta-adrenergic receptor agonists are known to stimulate muscle
      hypertrophy, the objective of this study was to determine whether ASB15 regulates
      cellular processes that contribute to muscle growth. Stable myoblast C2C12 cells
      expressing full-length ASB15 (ASB15-FL) and ASB15 lacking the ankyrin repeat
      (ASB15-Ank) or SOCS box (ASB15-SOCS) motifs were evaluated for changes in
      proliferation, differentiation, protein synthesis, and protein degradation.
      Expression of ASB15-FL caused a delay in differentiation, followed by an increase
      in protein synthesis of approximately 34% (P<0.05). A consistent effect of ASB15
      overexpression was observed in vivo, where ectopic expression of ASB15 increased
      skeletal muscle fiber area (P<0.0001) after 9 days. Expression of ASB15-SOCS
      altered differentiation of myoblasts, resulting in detachment of cells from
      culture plates. Expression of ASB15-Ank increased protein degradation by 84 h of
      differentiation (P<0.05), and in vivo ectopic expression of an ASB15 construct
      lacking both the ankyrin repeat and SOCS box motifs decreased skeletal muscle
      fiber area (P<0.0001). Together, these results suggest ASB15 participates in the
      regulation of protein turnover and muscle cell development by stimulating protein
      synthesis and regulating differentiation of muscle cells. This is the first study
      to demonstrate a role for an Asb family member in skeletal muscle growth.

PMID- 16424089
TI  - Textbook cricket goes to the field: the ecological scene of the neuroethological
      play.
AB  - Sensory ecology has recently emerged as a new focus in the study of how organisms
      acquire and respond to information from and about their environment. Many sensory
      scientists now routinely explore the physiological basis of sensing, such as
      vision, chemoreception or echolocation, in an ecological context. By contrast,
      research on one of the most performing sensors in the animal kingdom, the wind
      sensitive escape system of crickets and cockroaches, has failed so far to
      encompass ecological and evolutionary considerations. We report survival and
      behavioural experiments in which wood crickets interacted freely with natural
      predators in the field. Our results illustrate how the lack of knowledge about
      the ecology of these insects may entail our understanding of the biological
      relevance of their wind sensors. We found that predation pressure was most
      important on early stage crickets. Because laboratory studies have focused
      exclusively on adults' sensory systems, it is crucial that physical,
      physiological and neurobiological studies now turn to juveniles. Another common
      assumption challenged by our results is the nature of the air flow to which
      crickets are sensitive. Our results identify wolf spiders as the major predatory
      risk for wood crickets. Air movement stimuli produced by hunting spiders are
      likely to be strikingly different from air flows produced by flying insects. Yet,
      our theoretical understanding of air motion sensing is currently drawn from
      oscillatory flows of flying predators only.

PMID- 16424090
TI  - Rapid cold-hardening increases the freezing tolerance of the Antarctic midge
      Belgica antarctica.
AB  - Rapid cold-hardening (RCH) is well known to increase the tolerance of chilling or
      cold shock in a diverse array of invertebrate systems at both organismal and
      cellular levels. Here, we report a novel role for RCH by showing that RCH also
      increases freezing tolerance in an Antarctic midge, Belgica antarctica (Diptera,
      Chironomidae). The RCH response of B. antarctica was investigated under two
      distinct physiological states: summer acclimatized and cold acclimated. Summer
      acclimatized larvae were less cold tolerant, as indicated by low survival
      following exposure to -10 degrees C for 24 h; by contrast, nearly all cold
      acclimated larvae survived -10 degrees C, and a significant number could survive 
      15 degrees C. Cold-acclimated larvae had higher supercooling points than summer
      larvae. To evaluate the RCH response in summer-acclimatized midges, larvae and
      adults, maintained at 4 degrees C, were transferred to -5 degrees C for 1 h prior
      to exposures to -10, -15 or -20 degrees C. RCH significantly increased survival
      of summer-acclimatized larvae frozen at -10 degrees C for 1 h compared with
      larvae receiving no cold-hardening treatment, but adults, which live for only a
      week or so in the austral summer, lacked the capacity for RCH. In cold-acclimated
      larvae, RCH significantly increased freeze tolerance to both -15 and -20 degrees
      C. Similarly, RCH significantly increased cellular survival of fat body,
      Malpighian tubules and gut tissue from cold-acclimated larvae frozen at -20
      degrees C for 24 h. These results indicate that RCH not only protects against non
      freezing injury but also increases freeze tolerance.

PMID- 16424091
TI  - Freezing resistance of antifreeze-deficient larval Antarctic fish.
AB  - Antarctic notothenioids, along with many other polar marine fishes, have evolved
      biological antifreeze proteins (AFPs) to survive in their icy environments. The
      larvae of Antarctic notothenioid fish hatch into the same frigid environment
      inhabited by the adults, suggesting that they must also be protected by
      sufficient AFPs, but this has never been verified. We have determined the
      contribution of AFPs to the freezing resistance of the larvae of three species:
      Gymnodraco acuticeps, Pagothenia borchgrevinki and Pleuragramma antarcticum. Of
      the three, only P. borchgrevinki larvae are protected by high, adult levels of
      AFPs. Hatchling G. acuticeps and P. antarcticum have drastically inadequate AFP
      concentrations to avoid freezing at the ambient seawater temperature (-1.91
      degrees C). We raised G. acuticeps larvae and measured the AFP levels in their
      blood for approximately 5 months post hatching. Larval serum freezing point was 
      1.34+/-0.04 degrees C at the time of hatch; it began to decrease only after 30
      days post hatch (d.p.h.), and finally reached the adult value (-2.61+/-0.03
      degrees C) by 147 d.p.h. Additionally, AFP concentrations in their intestinal
      fluids were very low at hatching, and did not increase with age throughout a
      sampling period of 84 d.p.h. Surviving in a freezing environment without adequate
      AFP protection suggests that other mechanisms of larval freezing resistance
      exist. Accordingly, we found that G. acuticeps hatchlings survived to -3.6+/-0.1
      degrees C while in contact with external ice, but only survived to -1.5+/-0.0
      degrees C when ice was artificially introduced into their tissues. P. antarcticum
      larvae were similarly resistant to organismal freezing. The gills of all three
      species were found to be underdeveloped at the time of hatch, minimizing the risk
      of ice introduction through these delicate structures. Thus, an intact
      integument, underdeveloped gill structures and other physical barriers to ice
      propagation may contribute significantly to the freezing resistance and survival
      of these larval fishes in the icy conditions of the Southern Ocean.

PMID- 16424092
TI  - How bees tune their dancing according to their colony's nectar influx: re
      examining the role of the food-receivers' 'eagerness'.
AB  - Apis mellifera bees perform dances to communicate the presence of desirable
      nectar sources. The regulation of these dances does not depend exclusively on
      properties of the nectar sources, but also upon certain stimuli derived from the
      foraging status of the colony as a whole; i.e. bees exploiting a source of
      constant profitability are more likely to dance when the colony's nectar intake
      rate is low. Based on these stimuli, individual bees tune their dances according
      to their colony's nectar influx without visiting alternative nectar sources.
      Division of labour, in addition, is a common feature in honeybees. Upon returning
      to the nest, successful foragers transfer the content of their crops to food
      receivers by means of a common behaviour in social insects called trophallaxis,
      i.e. the transfer of liquid food by mouth. Martin Lindauer stated that a returned
      forager may sense the foraging status of its colony on the basis of the food
      transfer process by computing how quickly and eagerly the food-receivers unload
      its crop. This study focuses on the forager's experience during the food transfer
      process, its variability based on the colony's nectar influx, and the separate
      effects that the 'ease' and the 'eagerness' of the food-unloading have on the
      tuning of recruitment dances. Results indicate that foragers can rapidly sense
      variations in the colony's nectar influx, even when they experience no variation
      in the time interval between their return to the hive and the beginning of the
      food transfer. To accomplish this task they appear to use stimuli derived from
      the number of food-receivers, which enable them, in turn, to set their dance
      thresholds in relation to the nectar influx of their colony. The relevance of
      these findings is discussed in the context of communication and successful
      foraging.

PMID- 16424093
TI  - Ontogeny of mantle musculature and implications for jet locomotion in oval squid
      Sepioteuthis lessoniana.
AB  - We examined the relationship between mantle muscle structure and mantle
      kinematics in an ontogenetic series (5-85 mm dorsal mantle length) of oval squid,
      Sepioteuthis lessoniana. Thick filament length increased during growth in the
      mantle muscle fibres that power jet locomotion (i.e. the circular muscles). The
      thick filament length of both the superficial mitochondria-rich (SMR; analogous
      to vertebrate red muscle fibres) and central mitochondria-poor (CMP; analogous to
      vertebrate white muscle fibres) circular muscles increased significantly during
      ontogeny. Thick filaments in the SMR circular muscle fibres of newly hatched
      squid (N=5) ranged from 0.7 to 1.4 microm and averaged 1.0 microm, while the
      thick filaments of the SMR fibres of the largest squids (N=4) studied ranged from
      1.2 to 3.4 microm and averaged 1.9 microm. The ontogeny of thick filament length
      in the CMP circular muscle fibres showed a similar trend. The range for hatchling
      CMP circular muscles was 0.7-1.4 microm, with an average of 1.0 microm, whereas
      the range and average for the largest squids studied were 0.9-2.2 microm and 1.5
      microm, respectively. Within an individual hatchling, we noted no significant
      differences between the thick filament lengths of the SMR and CMP fibres. Within
      an individual juvenile, the thick filaments of the SMR fibres were approximately
      25% longer than the CMP fibres. The change in thick filament length may alter the
      contractile properties of the circular muscles and may also result in a decrease
      in the rate of mantle contraction during jetting. In escape-jet locomotion, the
      maximum rate of mantle contraction was highest in newly hatched squid and
      declined during ontogeny. The maximum rate of mantle contraction varied from 7-13
      muscle lengths per second in newly hatched squid (N=14) and from 3-5 muscle
      lengths per second in the largest squids (N=35) studied.

PMID- 16424094
TI  - The effect of endurance exercise on the morphology of muscle attachment sites.
AB  - The morphology of muscle attachment sites, or entheses, has long been assumed to
      directly reflect in vivo muscle activity. The purpose of this study is to examine
      whether variations in muscle activity that are within normal physiological limits
      are reflected in variations in external attachment site morphology. This study
      tests the hypothesis that increased muscle activity (magnitude, number and
      frequency of loading cycles) results in the hypertrophy of muscle attachment
      sites. The attachment sites of six limb muscles and one muscle of mastication
      (control) in mature female sheep were measured and compared in exercised
      (weighted treadmill running for 1 h per day for 90 days) and sedentary control
      animals. Attachment site surface morphology was assessed by quantifying the size
      (3D surface area) and complexity (fractal dimension parallel and perpendicular to
      soft tissue attachment) of the surfaces. The results of this study demonstrate no
      effect of the exercise treatment used in this experiment on any measure of
      enthesis morphology. Potential explanations for the lack of exercise response
      include the mature age of the animals, inappropriate stimulus type for inducing
      morphological change, or failure to surpass a hypothetical threshold of load for
      inducing morphological change. However, further tests also demonstrate no
      relationship between muscle size and either attachment site size or complexity in
      sedentary control animals. The results of this study indicate that the attachment
      site morphological parameters measured in this study do not reflect muscle size
      or activity. In spite of decades of assumption otherwise, there appears to be no
      direct causal relationship between muscle size or activity and attachment site
      morphology, and reconstructions of behavior based on these features should be
      viewed with caution.

PMID- 16424095
TI  - Dynamically similar locomotion in horses.
AB  - It is possible for animals of very different sizes to use the same patterns of
      locomotion, i.e. to move in a ;dynamically similar fashion'. This will only
      occur, however, if relevant biomechanical parameters scale with size in such a
      way that they compensate for the effects of size differences. Here we apply this
      principle to understanding the effects of size on locomotion within a species:
      the domestic horse. We predict that, without any factor to compensate for size
      differences, detectable deviations from dynamically similar locomotion would
      occur over the size range present in adult horses. We measured relative stride
      length (RSL) and duty factor (DF) in 21 trotting horses (body mass: 86-714 kg),
      and interpolated the data to predict RSL and DF at equivalent speeds (Froude
      numbers: 0.5, 0.75, 1.0). RSL and DF at equal Froude number were not
      significantly related to body mass. This is consistent with the hypothesis that
      horses trot in a dynamically similar fashion at equal Froude number. We show that
      the nonlinear stress-strain relationship of tendon can contribute to reducing
      deviations from dynamic similarity, ;buffering' the effects of variation in body
      mass, but conclude that this effect is unlikely to explain fully our results.
      This suggests that a ;compensatory distortion' may occur in horses, counteracting
      the effects of size differences. The approach used here is also applicable to
      understanding the consequences of size changes within an individual during
      growth.

PMID- 16424096
TI  - A comparative analysis of thermogenic capacity and cold tolerance in small birds.
AB  - Small birds showing marked seasonal changes in cold tolerance also exhibit winter
      increases in summit metabolic rate (Msum=maximum cold-induced thermogenesis or
      thermogenic capacity) relative to summer birds. However, some birds show modest
      seasonal changes in cold tolerance without winter increases in Msum and others
      exhibit large seasonal changes in cold tolerance with only minor changes in Msum.
      Thus, the degree of correlation between cold tolerance and Msum is uncertain and
      no interspecific study has directly addressed this question. In this study, we
      measured cold tolerance and Msum in summer- (21 species) and winter- (11 species)
      acclimatized birds from southeastern South Dakota. Msum was measured as the
      maximum oxygen consumption attained during exposure of individual birds to a
      declining series of temperatures in 79% helium/21% oxygen (helox). Cold tolerance
      was measured as the temperature at cold limit (TCL), which is the helox
      temperature that induced hypothermia in individual birds. Residuals from
      allometric regressions of logMsum and logTCL were significantly and negatively
      related for summer (R2=0.34, P=0.006) and winter (R2=0.40, P=0.037) birds. Data
      were also subjected to a comparative analyses with phylogenetically independent
      contrasts to remove potential confounding effects of phylogeny, and results were
      similar to the non-phylogenetic analyses, with significant negative correlations
      in both summer (R2=0.47, P<0.001) and winter (R2=0.40, P=0.049). Thus, birds with
      high Msum tended to show reduced TCL (i.e. high cold tolerance), suggesting that
      cold tolerance and summit metabolism are phenotypically linked in small birds.

PMID- 16424097
TI  - Heterogeneous perfusion of the paired gills of the abalone Haliotis iris Martyn
      1784: an unusual mechanism for respiratory control.
AB  - The abalone Haliotis iris retains the ancestral gastropod arrangement of a pair
      of bipectinate gills (ctenidia). The gills share a single branchial chamber, are
      supplied from a common haemolymph sinus and effectively support the whole of
      oxygen uptake by the animal. Using chronic indwelling cannulae and pulsed Doppler
      probes, post-branchial haemolymph oxygen partial pressures (PaO2) and haemolymph
      flow rates were measured in the left and right efferent ctenidial veins. During
      periods of internal hypoxia following emersion and handling, total branchial
      haemolymph flow (24.4+/-3.6 ml kg-1 min-1) was partitioned nearly equally between
      the left and right gills (13.3+/-2.6 and 10.8+/-1.4 ml kg-1 min-1, respectively)
      and their PaO2 values were similar (81.9+/-6.1 and 87.3+/-4.7 mmHg,
      respectively). In animals settled for >24 h, branchial haemolymph flow decreased
      to 9.1+/-2.1 ml kg-1 min-1, primarily resulting from a virtual shutdown of the
      left gill flow to only 4.6% of total flow (left, 0.41+/-0.34 ml kg-1 min-1;
      right, 8.6+/-2.0 ml kg-1 min-1). At rest, right gill PaO2 (85.5+/-6.8 mmHg) was
      essentially unchanged while PaO2 of the slowly perfused left gill rose to 105.3+/
      10.2 mmHg, close to the PO2 of the exhalant seawater (104.5+/-3.1 mmHg). The
      aerobic metabolic scope of H. iris therefore appears to be met primarily by
      circulatory adjustments at the left gill, which at rest is highly perfusion
      limited (left Ldiff, 0.14+/-0.07; right Ldiff, 0.44+/-0.08).

PMID- 16424098
TI  - Exposure to brackish water, upon feeding, leads to enhanced conservation of
      nitrogen and increased urea synthesis and retention in the Asian freshwater
      stingray Himantura signifer.
AB  - The white-edge freshwater whip ray Himantura signifer is ammonotelic in
      freshwater, but retains the capacities of urea synthesis and ureosmotic
      osmoregulation to survive in brackish water. The first objective of this study
      was to examine whether exposure to brackish water would lead to increases in food
      intake, and/or conservation of nitrogen in H. signifer upon daily feeding.
      Results obtained showed that a progressive increase in ambient salinity, from 1
      per thousand to 15 per thousand over a 10-day period, did not lead to an increase
      in daily food intake. However, there were significant reductions in daily rates
      of ammonia and urea excretion in H. signifer during salinity changes, especially
      between day 5 (in 10 per thousand water) and day 10 (in 15 per thousand water)
      when compared to those of the control kept in 1 per thousand water. Consequently,
      there was a significant decrease in the percentage of nitrogen (N) from the food
      being excreted as nitrogenous waste (ammonia-N+urea-N) during this period. On day
      10, the tissue urea contents in fish exposed to 15 per thousand water were
      significantly greater than those of fish kept in 1 per thousand water, and the
      excess urea-N accumulated in the former fish could totally account for the
      cumulative deficit in excretion of urea-N+ammonia-N during the 10-day period.
      Thus, it can be concluded that H. signifer is N-limited, and conserved more N
      from food when exposed to brackish water. The conserved N was converted to urea,
      which was retained in tissues for osmoregulation. The second objective of this
      study was to elucidate whether the retention of the capacity of N conservation in
      H. signifer would lead to an accumulation of urea in fish exposed to not only 15
      per thousand water, but also 1 per thousand water, upon feeding. For fish pre
      acclimated to 1 per thousand water or 15 per thousand water for 10 days and then
      fasted for 48 h, the rate of ammonia excretion in fish exposed to 15 per thousand
      water was consistently lower than that of fish exposed to 1 per thousand water,
      throughout the 36-h post-feeding period. In addition, the hourly rate of urea
      excretion in the former was significantly lower than that of the latter between
      hours 12 and 36. There were postprandial increases in ammonia contents in the
      muscle, liver, stomach, intestine, brain and plasma of fish kept in 1 per
      thousand water; but postprandial increases in ammonia occurred only in the liver
      and brain of fish exposed to 15 per thousand water, and the magnitudes of
      increases in the latter were smaller than those in the former. Indeed,
      postprandial increases in tissue urea contents occurred in both groups of fish,
      but the greatest increase in urea content was observed in the muscle of fish
      exposed to 15 per thousand water. Taken together, these results indicate that H.
      signifer in freshwater could be confronted with postprandial osmotic stress
      because of its capacity of conserving N and increasing urea synthesis upon
      feeding.

PMID- 16424099
TI  - Functions of the subesophageal ganglion in the medicinal leech revealed by
      ablation of neuromeres in embryos.
AB  - Two general trends in the evolution of the nervous system have been toward
      centralization of neuronal somata and cephalization of the central nervous system
      (CNS). These organizational trends are apparent in the nervous system of annelid
      worms, including leeches. To determine if the anterior brain of the leech serves
      functions similar to those of the brains of more complex organisms, including
      vertebrates, we ablated one of the two major regions of the cephalic brain--the
      subesophageal ganglion (SubEG). For anatomical reasons, ablations were performed
      in embryos, rather than in adults. At the end of embryonic development, we
      observed the leeches' spontaneous behaviour and their responses to moderate
      touch. We observed that, although the midbody ganglia of the leech CNS display a
      high degree of local autonomy, the cephalic brain provides generalized excitation
      to the rest of the CNS, is a source of selective inhibition that modulates
      behaviour, integrates sensory information from the head with signals from the
      rest of the body, and plays an important role in organizing at least some
      complicated whole-body behaviours. These roles of the leech cephalic brain are
      common features of brain function in many organisms, and our results are
      consistent with the hypothesis that they arose early in evolution and have been
      conserved in complex nervous systems.

PMID- 16424100
TI  - Early rearing environment impacts cerebellar growth in juvenile salmon.
AB  - The size and structure of an animal's brain is typically assumed to result from
      either natural or artificial selection pressures over generations. However,
      because a fish's brain grows continuously throughout life, it may be particularly
      responsive to the environmental conditions the fish experiences during
      development. Salmon are an ideal model system for studying these effects because
      natural habitats differ significantly from the hatchery environments in which
      these fish are frequently reared. For example, in the wild, salmon alevins (i.e.
      yolk-sac fry) are buried in the gravel, while hatchery environments lack this
      structural component. We show that the simple manipulation of adding stones to a
      standard rearing tank can dramatically alter the growth of specific brain
      structures in steelhead salmon alevins (Oncorhynchus mykiss). We found that
      alevins reared with stones grew brains with significantly larger cerebella than
      genetically similar fish reared in conventional tanks. This shift to a larger
      cerebellar size was, in turn, accompanied by changes in locomotory behaviors-
      behaviors that correlate strongly to the function of this brain region. We next
      show that hatchery fish reared in a more naturalistic setting in the wild had
      significantly larger brains than their lab-reared counterparts. However, relative
      cerebellar volumes were similar between wild-reared alevins and those reared in
      the complex treatment in the laboratory. Together our results indicate that,
      within the first three weeks of life, variation in rearing environment can result
      in brain differences that are commonly attributed to generations of selection.
      These results highlight the need to consider enrichment strategies when designing
      captive rearing facilities for both conservation and laboratory use.

PMID- 16424101
TI  - Corticotropin-releasing hormone-receptor 1 (CRH-R1) and CRH-binding protein (CRH
      BP) are expressed in the gills and skin of common carp Cyprinus carpio L. and
      respond to acute stress and infection.
AB  - We established that corticotropin-releasing hormone (CRH), CRH-binding protein
      (CRH-BP) and CRH-receptor 1 (CRH-R1) are expressed in the gills and skin of
      common carp Cyprinus carpio, an early vertebrate. Immunoreactive CRH was detected
      in macrophage-like cells in gills and skin, in fibroblasts in the skin and in
      endothelial cells in the gills. The involvement of the CRH system in gills and
      skin was investigated in response to infection and in an acute restraint stress
      paradigm. Carp were infected with the protozoan leech-transmitted blood
      flagellate Trypanoplasma borreli and subjected to acute restraint stress by
      netting for 24 h. The expression of CRH-BP and CRH-R1 genes in the gills and in
      the skin is downregulated after both infection and restraint. Thus the peripheral
      CRH system reacts to infection and stress. The gills and skin separate the
      internal from the external environment and are permanently exposed to stress and
      pathogens. Because of their pivotal role in maintaining the homeostatic
      equilibrium, these organs must act locally to respond to diverse stresses.
      Clearly, the CRH system is involved in the response of the integument to diverse
      stresses at the vulnerable interface of the internal and external milieu.

PMID- 16424102
TI  - The role of branchial carbonic anhydrase in acid-base regulation in rainbow trout
      (Oncorhynchus mykiss).
AB  - The objective of the present study was to examine the branchial distribution of
      the recently identified rainbow trout cytoplasmic carbonic anhydrase isoform
      (tCAc) and to investigate its role in the regulation of acid-base disturbances in
      rainbow trout (Oncorhynchus mykiss). In situ hybridization using an
      oligonucleotide probe specific to tCAc revealed tCAc mRNA expression in both
      pavement cells and mitochondria-rich cells (chloride cells). Similarly, using a
      homologous polyclonal antibody, tCAc immunoreactivity was localized to pavement
      cells and mitochondria-rich cells in the interlamellar region and along the
      lamellae of the gills. Exposure of rainbow trout to hypercarbia (approximately
      0.8% CO2) for 24 h resulted in significant increases in tCAc mRNA expression
      (approximately 20-fold; quantified by real-time PCR) and protein levels
      (approximately 1.3-fold; quantified by western analysis) but not enzyme activity
      (assessed on crude gill homogenates using the delta-pH CA assay). Inhibition of
      branchial CA activity in vivo using acetazolamide reduced branchial net acid
      excretion significantly by 20%. This effect was enhanced to a 36% reduction in
      branchial net acid excretion by subjecting the trout to hypercarbia
      (approximately 0.8% CO2) for 10 h prior to acetazolamide injection, an exposure
      that significantly increased branchial net acid excretion. The results of the
      present study support the widely held premise that branchial intracellular CA
      activity (tCAc) plays a key role in regulating acid-base balance in freshwater
      teleost fish.

PMID- 16424103
TI  - The neuropeptide proctolin potentiates contractions and reduces cGMP
      concentration via a PKC-dependent pathway.
AB  - As in many other arthropods, the neuropeptide proctolin enhances contractures of
      muscles in the crustacean isopod Idotea emarginata. The enhancement of high K+
      induced contractures by proctolin (1 micromol l-1) was mimicked upon application
      of the protein kinase C (PKC) activator phorbol-12-myristate 1-acetate (PMA) and
      was inhibited by the PKC inhibitor bisindolylmaleimide (BIM-1). The potentiation
      was not inhibited by H89, a protein kinase A (PKA) inhibitor. Proctolin did not
      change the intracellular concentration of 3',5'-cyclic adenosine monophosphate
      (cAMP) whereas it significantly reduced the intracellular concentration of 3',5'
      cyclic guanosine monophosphate (cGMP). The reduction of cGMP was not observed in
      the presence of the PKC inhibitor BIM-1. 8-Bromo-cGMP, a membrane-permeable cGMP
      analogue, reduced the potentiating effect of proctolin on muscle contracture. We
      thus conclude that proctolin in the studied crustacean muscle fibres induces an
      activation of PKC, which leads to a reduction of the cGMP concentration and,
      consequently, to the potentiation of muscle contracture.

PMID- 16424104
TI  - Effect of diet quality on carbon and nitrogen turnover and isotopic
      discrimination in blood of a New World nectarivorous bat.
AB  - Diet composition of carbon and nitrogen (C:N) could affect diet-tissue isotopic
      discrimination and elemental turnover rate in consumers but studies that test the
      nature of these changes are scarce. We compared carbon and nitrogen isotopic
      discrimination and turnover rates in individuals of Pallas' long-tongued bats
      Glossophaga soricina fed diets with protein soya isolate or amaranth grains as
      their main source of protein. Diets were of similar protein biological value but
      the soya diet had higher nitrogen content (2.2%N) and lower C:N ratio (39.6) than
      the amaranth diet (1.3%N, C:N=40.5). Most bats on the soya diet gained body mass
      whereas most bats on the amaranth diet lost body mass. Half-lives of carbon
      (24.3+/-3.8 days) and nitrogen (25.6+/-4.4 days) in bats switched to the soya
      diet were very similar. In contrast, in the bats switched to the amaranth diet,
      carbon half-life (39.7+/-3.4 days) was longer than that of nitrogen (25.0+/-6.0
      days). The enrichment in 15N between diet and blood was higher when bats were fed
      the amaranth diet (4.4+/-0.2 per thousand) than when they were fed the soya diet
      (3.3+/-0.2 per thousand). Similarly, bats on the amaranth diet had higher 13C
      enrichment (2.0+/-0.2 per thousand) than bats on the soya diet (0.1+/-0.1 per
      thousand). Our results support recent hypotheses of the effect of nutrition on
      diet-tissue isotopic discrimination and turnover rate, and further shows that
      blood stable isotope analysis is an adequate approach to track seasonal dietary
      shifts in wild bats.

PMID- 16424105
TI  - Significance of Na+ current in the excitability of atrial and ventricular
      myocardium of the fish heart.
AB  - The present study examines the importance of the Na+ current (INa) in the
      excitability of atrial and ventricular myocardium of the rainbow trout heart.
      Whole-cell patch-clamp under reduced sarcolemmal Na+ gradient showed that the
      density of INa is similar in atrial and ventricular myocytes of the trout heart,
      and the same result was obtained when INa was elicited by chamber-specific action
      potentials (AP) in normal physiological saline solution. However, the maximum
      rate (Vmax) of AP upstroke, measured with microelectrodes in intact trout heart,
      was 21% larger in atrium than ventricle, and thus in variance with the similar
      INa density of the two myocyte types. Furthermore, Vmax calculated from the INa
      was 2.1 and 3.2 times larger for atrium and ventricle, respectively, than the
      values obtained from the APs. The discrepancy between INa of isolated myocytes
      and Vmax of intact muscle is only partly explained by the inward rectifier K+
      current (IK1), which overlaps INa and decreases the net depolarising current.
      Clear differences exist in the voltage dependence of steady-state activation and
      inactivation as well as in the inactivation kinetics of INa between atrial and
      ventricular myocytes. As a result of a more negative voltage dependence of INa
      activation, smaller IK1 and higher input resistance of atrial myocytes, the
      voltage threshold for AP generation is more negative in atrium than ventricle of
      the trout heart. These findings suggest that atrial muscle is more readily
      excitable than ventricular muscle, and this difference is partly due to the
      properties of the atrial INa.

PMID- 16424106
TI  - The identification and role of a novel eicosanoid in the reproductive behaviour
      of barnacles (Balanus balanus).
AB  - Post-copulatory behaviour in barnacles involves a violent rocking movement of the
      opercular valves, which is thought to contribute to the expulsion of oocytes
      through the oviduct into the mantle cavity where they are fertilised. We
      demonstrate in this study that the seminal vesicles/testis of the subtidal
      barnacle Balanus balanus produce a biologically active factor, barnacle muscle
      stimulatory factor (BMSF), which causes a significant increase in cirral and body
      muscular activity. BMSF was identified using a combination of high performance
      liquid chromatography and mass spectrometry as a novel eicosanoid/oxylipin, 8,13
      dihydroxyeicosapentaenoic acid. This is rapidly inactivated under mild acid
      conditions to form a complex range of triene and pentaene chromophore-containing
      products that have only been partially identified. Injection of purified BMSF
      into the mantle cavity of barnacles caused the rocking movements of the opercular
      valves as reported following fertilisation. In excised barnacles, it also caused
      muscular contractions of the whole body mass. The breakdown products of BMSF,
      however, were without such activities. The function of BMSF in facilitating
      fertilisation in barnacles is comparable to the role of other eicosanoids in
      human reproduction, reinforcing the view that these compounds have conserved
      activities in both invertebrates and vertebrates.

PMID- 16424107
TI  - Corners and bubble wrap: the structure and texture of surfaces influence crayfish
      exploratory behaviour.
AB  - Touch is a principal sense in all animals. It is potentially important in species
      of freshwater crayfish that encounter murky waters or are nocturnal. Little is
      known about how tactile (touch) stimuli affect exploratory behaviour under these
      conditions. We placed animals in different tactile situations at the start of an
      exploration in a dark arena and tracked the position of the body and antennae to
      test whether subsequent search behaviour was affected. Individuals were exposed
      to differently textured walls, channelled out along a wall, or released in
      contact with no, one, or two walls. A corner arrangement of surfaces, where
      individuals started near two walls at right angles, produced behaviour that
      differed from that of other configurations; animals chose one wall and then
      maintained a close distance from the wall along which they were moving. The
      distance from a wall adopted by a crayfish walking parallel to it was affected by
      the texture of the wall. These results on the influence of tactile stimuli on
      crayfish exploratory behaviour may have implications for other taxa.

PMID- 16424109
TI  - Ginseng extract inhibits lipolysis in rat adipocytes in vitro by activating
      phosphodiesterase 4.
AB  - Elevated concentrations of plasma free fatty acids (FFA) may cause insulin
      resistance. Inhibition of lipolysis reduces FFA availability and improves insulin
      sensitivity. Ginseng extract (Panax spp., GE) was shown to improve glycemia in
      Type 2 diabetes. In the present study, the antilipolytic effect of GE in rat
      adipocytes and the signaling pathway for GE antilipolysis were investigated.
      Adipocytes were isolated from rat fat tissue by collagenase digestion. The
      ability of GE to inhibit lipolysis was assessed by measuring glycerol and FFA
      release into the incubation medium. Phosphatidylinositol 3-kinase (PI3-K)
      inhibitor and various phosphodiesterase (PDE) inhibitors were applied to
      investigate the signaling pathway for GE antilipolysis. The present study showed
      that insulin and GE inhibited lipolysis by 42.4 and 49% compared with basal,
      respectively (P < 0.05). Unlike insulin, the PI3-K inhibitor wortmannin did not
      reverse GE antilipolysis, and GE did not affect phosphorylation of protein kinase
      B (PKB). The nonselective PDE inhibitor enprofylline reversed both insulin and GE
      antilipolysis. The specific phosphodiesterase 3 (PDE3) inhibitor cilostamide
      reversed insulin antilipolysis completely, but did not significantly affect GE
      antilipolysis. The specific phosphodiesterase 4 (PDE4) inhibitor rolipram did not
      significantly affect insulin antilipolysis, but almost completely reversed GE
      antilipolysis. Moreover, the combination of PDE3 and PDE4 inhibitors completely
      reversed GE antilipolysis. None of the ginsenosides (Rb1, Re, Rg1, Rc, Rb2, and
      Rd) were responsible for GE antilipolysis. The results suggest that ginseng
      exerts its antilipolytic effect through a signaling pathway different from that
      of insulin. GE antilipolysis is mediated in part by activating PDE4 in rat
      adipocytes.

PMID- 16424108
TI  - Establishing glucose- and ABA-regulated transcription networks in Arabidopsis by
      microarray analysis and promoter classification using a Relevance Vector Machine.
AB  - Establishing transcriptional regulatory networks by analysis of gene expression
      data and promoter sequences shows great promise. We developed a novel promoter
      classification method using a Relevance Vector Machine (RVM) and Bayesian
      statistical principles to identify discriminatory features in the promoter
      sequences of genes that can correctly classify transcriptional responses. The
      method was applied to microarray data obtained from Arabidopsis seedlings treated
      with glucose or abscisic acid (ABA). Of those genes showing >2.5-fold changes in
      expression level, approximately 70% were correctly predicted as being up- or down
      regulated (under 10-fold cross-validation), based on the presence or absence of a
      small set of discriminative promoter motifs. Many of these motifs have known
      regulatory functions in sugar- and ABA-mediated gene expression. One promoter
      motif that was not known to be involved in glucose-responsive gene expression was
      identified as the strongest classifier of glucose-up-regulated gene expression.
      We show it confers glucose-responsive gene expression in conjunction with another
      promoter motif, thus validating the classification method. We were able to
      establish a detailed model of glucose and ABA transcriptional regulatory networks
      and their interactions, which will help us to understand the mechanisms linking
      metabolism with growth in Arabidopsis. This study shows that machine learning
      strategies coupled to Bayesian statistical methods hold significant promise for
      identifying functionally significant promoter sequences.

PMID- 16424110
TI  - Energy restriction lowers the expression of genes linked to inflammation, the
      cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue.
AB  - Using high-density oligonucleotide microarrays, we examined the actions of energy
      restriction (ER) on the expression of >11,000 genes in epididymal white adipose
      tissue (WAT) of 10- to 11-mo-old male C57Bl6 mice. Four groups were studied:
      controls not subjected to food restriction (CO), food-restricted 18 h before
      being killed (FR), short-term ER for 23 d (SER), and long-term ER for 9 mo (LER).
      As we reported previously, compared with CO mice, FR and SER minimally influenced
      the gene expression profiles; however, 345 transcripts of 6,266 genes determined
      to be expressed in WAT were significantly altered by LER. We focus here on the
      109 (31%) of these genes that were involved in either inflammation (56 genes),
      cytoskeleton (16 genes), extracellular matrix (23 genes), or angiogenesis (14
      genes). Among these 109 genes, 104 transcripts (95%) were down regulated by LER.
      Western blotting for heat shock protein 47 and osteonectin, and
      immunohistochemical staining for hypoxia inducible factor (HIF)-1alpha),
      supported the microarray data that LER down regulated the expressions of these
      genes. Additionally, a 75% reduction in adipocyte size with LER reflected the
      change in the expression of genes involved in cell morphology. Our findings
      provide evidence that LER suppresses the expression of genes encoding
      inflammatory molecules in WAT while promoting structural remodeling of the
      cytoskeleton, extracellular matrix, and vasculature. These alterations may play
      an important role in the protection against WAT-derived inflammation and in
      lifespan extension by LER.

PMID- 16424111
TI  - Trans-10, cis-12- and cis-9, trans-11-conjugated linoleic acid isomers
      selectively modify HDL-apolipoprotein composition in apolipoprotein E knockout
      mice.
AB  - Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote
      atherosclerosis in mice despite increasing blood concentrations of HDL
      cholesterol. This suggests that under these conditions, the HDL apolipoproteins
      (apo) produced are abnormal. To test this hypothesis, apoE-deficient mice were
      fed a Western-type diet enriched with linoleic acid (control), cis-9, trans-11
      CLA or trans-10, cis-12-CLA (1.0% wt/wt) for 12 wk, and the effects on HDL
      metabolism and apoC-III levels recorded. Compared with the control and cis-9,
      trans-11-CLA mice, those fed the trans-10, cis-12-CLA diet had significantly
      higher HDL cholesterol concentrations, and had a higher incidence of
      hypertriglyceridemia and hepatic steatosis. Plasma apoA-I and paraoxonase
      concentrations were significantly lower in the trans-10, cis-12-CLA group than in
      the cis-9, trans-11-CLA group. These reductions were associated with decreased
      hepatic expression of these proteins and a shift toward lipid-poor apolipoprotein
      particles. The plasma apoA-II concentration increased with its corresponding mRNA
      concentration in the liver, and was preferentially bound to HDL in the trans-10,
      cis-12-CLA mice, thus explaining the increased HDL cholesterol concentrations in
      this group. Significant, positive associations were found between apoA-II and C
      III (r=0.883, P<0.001) and between apoA-II and atherosclerosis (r=0.68, P<0.001).
      These results indicate that trans-10, cis-12-CLA intake modifies HDL to form a
      proatherogenic apoA-II containing particle and promotes phenotypic changes
      compatible with metabolic syndrome. Cis-9, trans-11-CLA does not promote this
      detrimental effect.

PMID- 16424112
TI  - The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis,
      protects mice against lethal endotoxemia and sepsis.
AB  - Despite recent advances in antibiotic therapy and intensive care, sepsis remains
      a widespread problem in critically ill patients. The high mortality from sepsis
      is in part mediated by bacterial endotoxin, which stimulates
      macrophages/monocytes to sequentially release early (e.g., tumor necrosis factor,
      interleukin-1, and interferon-gamma) and late [e.g., high mobility group box 1
      protein (HMGB1)] proinflammatory cytokines. Our discovery of HMGB1 as a late
      mediator of lethal systemic inflammation has initiated a new field of
      investigation for the development of experimental therapeutics. A popular Chinese
      herb, Angelica sinensis (also known as Dang Gui or Dong Quai) has been used
      traditionally for treating women with gynecological disorders (such as
      dysmenorrheal and hot flashes). Here we examined the effect of Angelica sinensis
      extract on endotoxin-induced HMGB1 release in vitro, and explored its therapeutic
      potential in animal models of lethal endotoxemia and sepsis [induced by cecal
      ligation and puncture (CLP)] in vivo. We demonstrated that a low-molecular-weight
      (<10 kDa) fraction of A. sinensis extract significantly attenuated endotoxin
      induced HMGB1 release in part through interfering with its cytoplasmic
      translocation in macrophage cultures. Prophylactic administration of an aqueous
      extract of A. sinensis significantly attenuated systemic HMGB1 accumulation in
      vivo, and conferred a dose-dependent protection against lethal endotoxemia.
      Furthermore, delayed administration of A. sinensis extract beginning 24 h after
      CLP attenuated systemic HMGB1 accumulation, and significantly rescued mice from
      lethal sepsis. Taken together, these data suggest that A. sinensis contains water
      soluble components that exert protective effects against lethal endotoxemia and
      experimental sepsis in part by attenuating systemic accumulation of a late
      proinflammatory cytokine, HMGB1.

PMID- 16424113
TI  - Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1
      activation and IL-6 gene transcription in mouse macrophages.
AB  - The mycotoxin deoxynivalenol (DON) induces IgA nephropathy in mice by
      upregulating IL-6 expression, which is suppressed by (n-3) PUFA consumption. The
      purpose of this study was to test the hypothesis that consumption of the (n-3)
      PUFA docosahexaenoic acid (DHA) interferes with DON-induced transcriptional and
      post-transcriptional upregulation of IL-6 mRNA in murine macrophages. DON evoked
      expression of IL-6 mRNA and IL-6 heterogenous nuclear RNA (hnRNA), an indicator
      of ongoing IL-6 transcription, in macrophages elicited from mice fed control AIN
      93G diet for 4 wk, whereas expression of both RNA species was suppressed in
      macrophages from mice fed AIN-93G modified to contain 30 g DHA/kg diet for the
      same time period. DON enhanced IL-6 mRNA stability similarly in macrophages from
      control and DHA-fed mice suggesting that (n-3) PUFA effects were not post
      transcriptional. DON upregulated binding activity of cAMP response element
      binding protein (CREB) and activator protein (AP-1) to their respective consensus
      sequences in nuclear extracts from control-fed mice, whereas both activities were
      suppressed in nuclear extracts from DHA-fed mice. DON induced phosphorylation of
      CREB at Ser-133 and ATF1 at Ser-63 as well as intranuclear binding of phospho
      CREB/ATF1 to the cis element of the IL-6 promoter in control macrophages, whereas
      both activities were inhibited in macrophages from DHA-fed mice. DHA consumption
      blocked DON-induced phosphorylation of the CREB kinase AKT. Inhibition of AKT
      suppressed both CREB/ATF1 phosphorylation and IL-6 transcription. These data
      suggest that DHA consumption suppresses DON-induced IL-6 transcription in
      macrophages in part by interfering with AKT-dependent phosphorylation and
      subsequent binding of CREB/ATF1 to the IL-6 promoter.

PMID- 16424114
TI  - Plasma glutathione and cystathionine concentrations are elevated but cysteine
      flux is unchanged by dietary vitamin B-6 restriction in young men and women.
AB  - Cysteine synthesis from homocysteine is catalyzed by two pyridoxal 5'-phosphate
      (PLP)-dependent enzymes. This suggests that vitamin B-6 status might affect
      cysteine and glutathione homeostasis, but it is unclear whether this occurs in
      humans. We assessed the effects of vitamin B-6 status on static and kinetic
      parameters of cysteine and glutathione metabolism in healthy female (n=5) and
      male (n=4) volunteers (20-30 y) before and after 4 wk of dietary vitamin B-6
      restriction (<0.5 mg vitamin B-6/d). Rates of reactions related to cysteine
      metabolism were measured from blood sampled during primed, constant infusions of
      [(13)C(5)]methionine, [3-(13)C]serine, and [(2)H(2)]cysteine that were conducted
      after an overnight fast at baseline and after the dietary protocol. Vitamin B-6
      restriction reduced the concentration of PLP (55.1+/- 8.3 vs. 22.6+/-1.3 nmol/L;
      P=0.004) and increased concentrations of cystathionine (124%; P<0.001) and total
      glutathione (38%; P<0.008) in plasma. Concentrations of plasma homocysteine,
      cysteine, cysteinylglycine, and C-reactive protein (an indicator of systemic
      inflammation) were not affected by dietary vitamin B-6 restriction. The rate of
      cysteine synthesis via transsulfuration was below detection limits in this
      protocol. Neither the fractional synthesis rate of cystathionine nor whole-body
      cysteine flux was affected by vitamin B-6 restriction. These data indicate that
      glutathione homeostasis is altered by dietary vitamin B-6 deficiency and appears
      to be unrelated to cysteine flux under conditions of minimal amino acid intake as
      evaluated in this study.

PMID- 16424115
TI  - Aerobic exercise training increases skeletal muscle protein turnover in healthy
      adults at rest.
AB  - The effect of a 4-wk aerobic exercise training program (30-45 min, 3-5 d/wk,
      >or=65% maximal heart rate) on mixed skeletal muscle protein fractional synthetic
      rate (FSR), fractional breakdown rate (FBR), and net protein balance (FSR - FBR)
      (NET) was examined in 8 healthy, previously unfit men and women [21.0+/- 0.4 y,
      163.7+/- 4.4 cm, 75.6+/- 5.7 kg, 33.5+/- 4.1% body fat, VO(2 peak) 38.6+/- 2.3
      mL/(kg.min)] fed eucaloric diets providing 0.85 g protein/(kg.d) for the 6-wk
      study. Measurements were made at baseline after 2 wk of diet intervention only,
      and after 4 wk of aerobic exercise training and diet intervention. Primed
      continuous infusions of ring-[(2)H(5)]-phenylalanine (2 micromol/kg; 0.05
      micromol/(kg.min) and [(15)N]-phenylalanine (2 micromol/kg; 0.05
      micromol/(kg.min) were used to assess skeletal muscle protein turnover at rest
      via the precursor-product method. Endurance training improved cardiovascular
      fitness, with a significant increase in VO(2 peak) (P<0.01) and a significant
      decrease in running time on a standard course (P<0.01). There were o significant
      changes in body mass or composition. There was a significant increase in FSR
      (0.077+/- 0.007 vs. 0.089+/- 0.006%/h, P<0.05) and decrease in NET (FSR - FBR) (
      0.023 +/-0.004 vs. -0.072 +/- 0.012%/h, P < 0.05); FBR tended to increase
      (0.105+/- 0.014 vs. 0.143+/- 0.018%/h; P=0.06) after training. Findings show that
      aerobic training for 4 wk increases skeletal muscle protein turnover in
      previously unfit subjects.

PMID- 16424116
TI  - Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL,
      and HDL subfraction distribution and size in overweight men.
AB  - To determine the effects of carbohydrate restriction (CR) with and without
      soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight
      loss intervention. Subjects were matched by age and BMI and randomly assigned to
      consume 3 g/d of either a soluble fiber supplement (n=14) or placebo (n=15) with
      a macronutrient energy distribution of approximately 10% carbohydrate,
      approximately 65% fat, and approximately 25% protein. Because the groups did not
      differ in any of the variables measured, all data were pooled and comparisons
      were made between baseline and 12 wk. After 12 wk, subjects had a mean weight
      loss of 7.5 kg (P<0.001), and abdominal fat was reduced by 20% (P<0.001). Plasma
      LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and
      38.6%, respectively. Similarly, apolipoproteins C-I (-13.8%), C-III (-21.2%) and
      E (-12.5%) were significantly lower after the intervention. In contrast plasma
      HDL-cholesterol concentrations were increased by 12% (P<0.05). Changes in plasma
      TG were positively correlated with reductions in large (r=0.615, P<0.01) and
      medium VLDL particles (r=0.432, P<0.05) and negatively correlated with LDL
      diameter (r=-0.489, P<0.01). Changes in trunk fat were positively correlated with
      medium VLDL (r=0.474, P<0.0) and small LDL (r=0.405, P<0.05) and negatively
      correlated with large HDL (r=-0.556, P<0.01). We conclude that weight loss
      induced by CR favorably alters the secretion and processing of plasma
      lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased
      risk for atherosclerosis and coronary heart disease.

PMID- 16424117
TI  - Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice.
AB  - When pyrroloquinoline quinone (PQQ) is added to an amino acid-based, but
      otherwise nutritionally complete basal diet, it improves growth-related variables
      in young mice. We examined PQQ and mitochondrial function based on observations
      that PQQ deficiency results in elevated plasma glucose concentrations in young
      mice, and PQQ addition stimulates mitochondrial complex 1 activity in vitro. PQQ
      deficient weanling mice had a 20-30% reduction in the relative amount of
      mitochondria in liver; lower respiratory control ratios, and lower respiratory
      quotients than PQQ-supplemented mice (2 mg PQQ/kg diet). In mice from dams fed a
      conventional laboratory diet, but switched at weaning to the basal diet, plasma
      glucose, Ala, Gly, and Ser concentrations were elevated at 4 wk (PQQ- vs. PQQ+),
      but not at 8 wk. The relative mitochondrial content (ratio of mtDNA to nuclear
      DNA) also tended (P<0.18) to be lower (PQQ- vs. PQQ+) at 4 wk, but not at 8 wk.
      PQQ also counters the mitochondrial complex 1 inhibitor, diphenylene iodonium
      (DPI). Mice were gavaged with 0, 0.4, or 4 microg PQQ/g body weight (BW) daily
      for 14 d. At each PQQ level, DPI was injected (i.p.) at 0, 0.4, 0.8, or 1.6
      microg DPI/g BW. The PQQ-deficient mice exposed to 0.4 or 4.0 microg DPI/g lost
      weight and had lower plasma glucose levels than PQQ-supplemented mice (P<0.05).
      In addition, fibroblasts took up (3)H-PQQ added to cell cultures, and cultured
      hepatocytes maintained mitochondrial PQQ concentrations similar to those observed
      in vivo. Collectively, these results indicate that dietary PQQ can influence
      mitochondrial amount and function, particularly in perinatal and weanling mice.

PMID- 16424118
TI  - Polyunsaturated fatty acid supplementation during pregnancy alters neonatal
      behavior in sheep.
AB  - The objectives of the study were to determine whether supplementation of pregnant
      ewes with long-chain (n-3) fatty acids present in fish oil, in combination with
      dietary vitamin E, would alter neonatal behavior in sheep. Twin- (n=36) and
      triplet- (n=12) bearing ewes were allocated at d 103 of gestation to 1 of 4
      dietary treatments containing 1 of 2 fat sources [Megalac, a calcium soap of palm
      fatty acid distillate or a fish oil mixture, high in 20:5(n-3) and 22:6(n-3)] and
      1 of 2 dietary vitamin E concentrations (50 or 500 mg/kg) in a 2 x 2 factorial
      design. Feeding fish oil increased gestation length by 2 d and increased the
      proportion of 22:6(n-3) within neonatal plasma by 5.1-fold and brain by 10%,
      whereas brain 20:5(n-3) was increased 5-fold. Supranutritional dietary vitamin E
      concentrations decreased the latency of lambs to stand in ewes fed fish oil but
      not Megalac, whereas latency to suckle was decreased from 43 to 34 min by fish
      oil supplementation. Supplementation with fish oil also substantially decreased
      the secretion rate (mL/h) of colostrum and the yield (g/h) of fat and protein. We
      conclude that supplementation of ewes with fish oil decreases the latency to
      suckle, increases gestation length and the 22:6(n-3):20:4(n-6) ratio in the
      neonatal brain, and may improve lamb survival rate. However, further work is
      required to determine how to mitigate the negative effects of fish oil on
      colostrum production.

PMID- 16424119
TI  - Bioavailability is improved by enzymatic modification of the citrus flavonoid
      hesperidin in humans: a randomized, double-blind, crossover trial.
AB  - Hesperidin is the predominant polyphenol consumed from citrus fruits and juices.
      However, hesperidin is proposed to have limited bioavailability due to the
      rutinoside moiety attached to the flavonoid. The aim of this study was to
      demonstrate in human subjects that the removal of the rhamnose group to yield the
      corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the
      bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed
      the double-blind, randomized, crossover study. Subjects randomly consumed
      hesperetin equivalents supplied as orange juice with natural hesperidin ("low
      dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7
      glucoside, and orange juice fortified to obtain 3 times more hesperidin than
      naturally present ("high dose"). The area under the curve (AUC) for total plasma
      hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher
      than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs.
      1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after
      consuming the hesperetin-7-glucoside juice was improved to the level of the
      "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma
      concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L,
      P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with
      those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold
      higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L).
      The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects
      consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and
      "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study
      demonstrated that the bioavailability of hesperidin was modulated by enzymatic
      conversion to hesperetin-7-glucoside, thus changing the absorption site from the
      colon to the small intestine. This may affect future interventions concerning the
      health benefits of citrus flavonoids.

PMID- 16424120
TI  - Genistein decreases food intake, body weight, and fat pad weight and causes
      adipose tissue apoptosis in ovariectomized female mice.
AB  - Genistein, an isoflavone in soybean products, has estrogenic activity and is used
      as a natural substitute for estrogen replacement therapy in postmenopausal women.
      Genistein was also shown to decrease fat pad weight in female mice. The primary
      objective of this study was to determine the effect of genistein on adipose
      tissue apoptosis in vitro and in vivo. 3T3-L1 preadipocytes and mature adipocytes
      were treated with 0, 1, 10, 100, and 400 micromol/L genistein and then assayed
      for apoptosis, whereas only mature adipocytes were assayed for viability. Mature
      adipocytes treated with genistein demonstrated a dose-related increase in
      apoptosis. Ovariectomized female mice (9 mo old) were given 0, 150, or 1,500
      mg/kg genistein in the semipurified phytoestrogen-free casein-based diet for 3 wk
      (n=10). After mice were killed, body composition was determined by dual-energy X
      ray absorptiometry analysis, and parametrial (PM), inguinal (ING), and
      retroperitoneal (RP) fat pads were weighed and assayed for apoptosis (% DNA
      fragmentation). Genistein (1500 mg/kg) reduced food intake (FI) by 14% (P<0.01)
      and body weight (BW) by 9% (P<0.01). Body composition was not significantly
      affected, but PM and ING weights were decreased 22% (P<0.05) and 19% (P<0.07),
      respectively, by 1,500 mg/kg genistein. Apoptosis in ING fat was increased 290%
      (P<0.05) by 1,500 mg/kg genistein. These findings show that oral genistein
      treatment can reduce BW, mobilize body fat, and induce apoptosis of adipose
      tissue in ovariectomized female mice. Thus, genistein may be useful in treating
      or preventing increased adiposity after menopause.

PMID- 16424121
TI  - Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo
      in obese, insulin-resistant JCR:LA-cp rats.
AB  - Chromium is one of the few trace minerals for which a specific cellular mechanism
      of action has not been identified. Recent in vitro studies suggest that chromium
      supplementation may improve insulin sensitivity by enhancing insulin receptor
      signaling, but this has not been demonstrated in vivo. We investigated the effect
      of chromium supplementation on insulin receptor signaling in an insulin-resistant
      rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were
      randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or
      vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and
      based on calculated water intake, rats randomized to CrPic received 80
      microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis)
      biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin
      stimulation to assess insulin signaling. Obese rats treated with CrPic had
      significantly improved glucose disposal rates and demonstrated a significant
      increase in insulin-stimulated phosphorylation of insulin receptor substrate
      (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle
      compared with obese controls. The increase in cellular signaling was not
      associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt.
      However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower
      in obese rats administered CrPic than obese controls. When corrected for protein
      content, PTP1B activity was also significantly lower in obese rats administered
      CrPic than obese controls. Our data suggest that chromium supplementation of
      obese, insulin-resistant rats may improve insulin action by enhancing
      intracellular signaling.

PMID- 16424122
TI  - Conjugated linoleic acid attenuates cyclooxygenase-2 transcriptional activity via
      an anti-AP-1 mechanism in MCF-7 breast cancer cells.
AB  - Overexpression of cyclooxygenase-2 (COX-2) is regarded as a causative factor in
      the onset of tumorigenesis of the breast. In this study, we investigated the
      effects of conjugated linoleic acid (CLA) on COX-2 transcription in MCF-7 breast
      cancer cells. Results of transient transfection studies revealed that treatment
      with a CLA mix or selected isomers (c9, t11-CLA; t10, c12-CLA) at concentrations
      ranging from 20 to 80 micromol/L, attenuated COX-2 transcription induced by the
      proinflammatory agent 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition,
      the CLA mix inhibited TPA-induced activity of the collagenase-1 promoter. Using
      electrophoretic mobility shift assays, we found that the CLA mix reduced TPA
      induced recruitment of nuclear proteins to a cAMP response element (CRE) in the
      COX-2 promoter and a consensus TPA-responsive element (TRE) in the collagenase-1
      promoter. Both CRE and TRE are binding sites for activator protein-1 (AP-1).
      Binding studies revealed that the t10, c12-CLA isomer was more effective than the
      CLA mix or c9, t11-CLA in reducing binding of cJun to either the COX-2 CRE or
      collagenase-1 TRE, whereas linoleic acid increased binding to both elements.
      Overexpression of the AP-1 member, c-Jun, reversed the inhibitory effects of the
      CLA mix on COX-2 transcription, and restored binding of nuclear proteins to the
      CRE and TRE. Collectively, these results suggest that CLA represses AP-1-mediated
      activation of COX-2 transcription.

PMID- 16424123
TI  - Walnuts reduce aortic ET-1 mRNA levels in hamsters fed a high-fat, atherogenic
      diet.
AB  - Walnut consumption is associated with reduced coronary vascular disease (CVD)
      risk; however, the mechanisms responsible remain incompletely understood. Recent
      clinical studies suggested that these mechanisms involve non-plasma lipid-related
      effects on endothelial function. Male Golden Syrian hamsters (12 groups, n=10-15)
      were fed for 26 wk atherosclerotic, high-fat, hyperlipidemic diets with
      increasing concentrations of whole walnuts (61-150 g/kg diet), or alpha
      tocopherol (alpha-T, 8.1-81 mg/kg diet) and single diets with either walnut oil
      (32 g/kg diet) or pure gamma-tocopherol (gamma-T; 81 mg/kg diet) added. Aortic
      endothelin 1 (ET-1), an important endothelial regulator, was assayed as mRNA.
      Aortic cholesterol ester (CE) concentration along with other vascular stress
      markers (Cu/Zn and Mn superoxide dismutase, biliverdin reductase) and plasma
      lipid concentrations were determined. Hyperlipidemia (plasma LDL cholesterol
      approximately 6 times normal) occurred in all groups. Aortic CE concentration, a
      measure of atherosclerotic plaque, was highest in the lowest alpha-T only group
      and declined significantly with increasing alpha-T. The aortic CE of all walnut
      groups was decreased significantly relative to the lowest alpha-T only group but
      showed no dose response. The diets did not produce changes in the other vascular
      stress markers, whereas aortic ET-1 mRNA levels declined dramatically with
      increasing dietary walnuts (to a 75% reduction in the highest walnut content
      group compared with the lowest alpha-T group) but were unaltered in the alpha-T
      groups or gamma-T group. The study results are consistent with those of human
      walnut feeding studies and suggest that the mechanisms underlying those results
      are mediated in part by ET-1-dependent mechanisms. The contrasting results
      between the alpha-tocopherol or gamma-tocopherol diets and the walnut diets also
      make it unlikely that the non-plasma lipid-related CVD effects of walnuts are due
      to their alpha-tocopherol or gamma-tocopherol content. Finally, the results
      indicate that the walnut fat compartment is a likely location for the components
      responsible for the reduced aortic CE concentration.

PMID- 16424124
TI  - A mixture of the Salacia reticulata (Kotala himbutu) aqueous extract and
      cyclodextrin reduces the accumulation of visceral fat mass in mice and rats with
      high-fat diet-induced obesity.
AB  - The effects of a mixture of the Salacia reticulata (Kotala himbutu) aqueous
      extract and cyclodextrin (SRCD) on the development of obesity were examined. We
      studied the effects of SRCD on the elevation of plasma triacylglycerol levels
      induced by oral administration of a high-fat (HF) liquid diet to male Sprague
      Dawley rats. The plasma triacylglycerol concentration was significantly lower in
      the SRCD-treated rats than in the control rats 4 h after HF diet administration
      (P<0.05). In a study of female C57BL/6 mice that consumed a solid HF diet
      containing 0, 0.2 or 0.5% SRCD ad libitum for 8 wk, the increases in body weight
      and visceral fat mass were less in those fed the diet supplemented with 0.5% SRCD
      than in those fed the HF diet (P<0.05). In male Sprague-Dawley rats fed a solid
      HF diet with or without 0.2% SRCD and restricted in energy intake to that of rats
      fed a normal diet for 35 d, the increases in body weight and visceral fat mass
      were smaller in the SRCD-supplemented rats (P<0.05). In addition, the energy
      efficiency and the plasma leptin and adiponectin concentrations were lower in the
      mice and rats that were administered SRCD than in those fed the HF diet alone
      (P<0.05). The inhibitory effects of SRCD on HF diet-induced obesity may be
      attributable to the inhibition of carbohydrate and lipid absorption from the
      small intestine. Therefore, SRCD may suppress the accumulation of visceral fat
      and the glucose intolerance that accompany this type of obesity.

PMID- 16424125
TI  - A debriefing session with a nutritionist can improve dietary assessment using
      food diaries.
AB  - The objective of the current study was to evaluate the effect of a debriefing
      call on nutrient intake estimates using two 3-d food diaries among women
      participating in the Women's Health and Interview Study (WISH) Diet Validation
      Study. Subjects were 207 women with complete data and six 24-h recalls (24-HR) by
      telephone over 8 mo followed by two 3-d food diaries during the next 4 mo.
      Nutrient intake was assessed using the food diaries before and after a debriefing
      session by telephone. The purpose of the debriefing call was to obtain more
      detailed information on the types and amounts of fat in the diet. However, due to
      the ubiquitous nature of fat in the diet, the debriefing involved providing more
      specific detail on many aspects of the diet. There was a significant difference
      in macronutrient and micronutrient intake estimates after the debriefing.
      Estimates of protein, carbohydrate, and fiber intake were significantly higher
      and total fat, monounsaturated fat, saturated fat, vitamin A, vitamin C, alpha
      tocopherol, folic acid, and calcium intake were significantly lower after the
      debriefing (P < 0.05). The limits of agreement between the food diaries before
      and after the debriefing were especially large for total fat intake, which could
      be under- or overestimated by approximately 15 g/d. The debriefing call improved
      attenuation coefficients associated with measurement error for vitamin C, folic
      acid, iron, alpha tocopherol, vitamin A, and calcium estimates. A hypothetical
      relative risk (RR) = 2.0 could be attenuated to 1.16 for folic acid intake
      assessed without a debriefing but to only 1.61 with a debriefing. Depending on
      the nutrients of interest, the inclusion of a debriefing can reduce the potential
      attenuation of RR in studies evaluating diet disease associations.

PMID- 16424126
TI  - Dietary intake and risk of coronary heart disease differ among ethnic subgroups
      of black Americans.
AB  - Coronary heart disease (CHD) morbidity and mortality are more prevalent in Blacks
      than Whites in the United States. Most studies evaluate the dietary intake and
      health of Black Americans as one group and do not consider possible differences
      among ethnic subgroups within the U.S. Black population. We used data from NHANES
      III to assess whether dietary intake, CHD risk factors, and predicted 10-y risk
      of CHD differed between non-Hispanic Black adults born in the United States (NHB
      US), and non-Hispanic and Hispanic Black adults born outside of the United States
      (NHB-non US, HB-non US). Data were provided from single 24-h dietary recalls,
      biochemical measures, the medical examination, and self-reported responses to
      survey questions. NHB-US had higher intakes of energy, fat, protein, meat, added
      sugars, and sodium, and lower intakes of fruits, fiber, and most micronutrients.
      NHB-US also had higher predicted 10-y risk of developing CHD (5.8%) than NHB-non
      US (3.7%, P<0.001) or HB-non US (4.7%, P=0.017). Both immigrant groups had better
      CHD risk profiles and lower proportions of persons with metabolic syndrome and
      other CHD-related conditions. Our findings show differences in dietary intake and
      risk of CHD and related health conditions among ethnic subgroups of Blacks living
      in the United States. Future studies of diet and health should consider cultural
      differences within the Black population to better understand and reduce overall
      health disparities in the United States.

PMID- 16424127
TI  - Risk of infant anemia is associated with exclusive breast-feeding and maternal
      anemia in a Mexican cohort.
AB  - The WHO recommends exclusive breast-feeding (EBF) for the first 6 mo of life to
      decrease the burden of infectious disease. However, some are concerned about the
      effect of EBF >6 mo on iron status of children in developing countries in which
      anemia is prevalent. This study examines the risk of anemia in relation to the
      duration of EBF and maternal anemia in a birth cohort studied between March 1998
      and April 2003. All infant birth weights were >or=2.2 kg. All mothers received
      home-based peer counseling to promote EBF. Infant feeding data were collected
      weekly. Nurses measured hemoglobin (Hb) values every 3 mo. Hb was measured in 183
      infants at 9 mo of age. Anemia at 9 mo was defined as a Hb value <100 g/L. EBF
      was defined by WHO criteria and ranged in duration from 0 to 31 wk. At 9 mo, Hb
      (mean +/- SEM) was 114 +/- 0.9 g/L; 23 children (12.5%) had Hb levels <100 g/L.
      EBF >6 mo, but not EBF 4-6 mo, was associated with increased risk of infant
      anemia compared with EBF <4 mo (odds ratio=18.4, 95% CI=1.9, 174.0). Maternal
      anemia was independently (P=0.03) associated with a 3-fold increased risk of
      infant anemia. These associations were not explained by confounding with other
      maternal or infant factors. By linear regression, a lower infant Hb at 9 mo was
      associated with increased EBF duration among mothers who had a history of anemia
      (beta=-0.07, P=0.003), but not among mothers with no history of anemia. Infants
      who are exclusively breast-fed for >6 mo in developing countries may be at
      increased risk of anemia, especially among mothers with a poor iron status;
      greater attention to this issue is warranted.

PMID- 16424128
TI  - Relative validity of food intake estimates using a food frequency questionnaire
      is associated with sex, age, and other personal characteristics.
AB  - We investigated the validity of food intake estimates obtained by a self
      administered FFQ relative to weighed food records (WFR) and the extent to which
      demographic, anthropometric, and social characteristics explain differences
      between these methods. A community-based sample of 96 Australian adults completed
      a FFQ and 12 d of WFR over 12 mo. The FFQ was adapted to the Australian setting
      from the questionnaire used in the US Nurses' Health Study. Spearman rank
      correlation coefficients ranged from 0.08 for "other vegetables" to 0.88 for tea.
      Exact agreement by quartiles of intake ranged from 27% (eggs) to 63% (tea).
      Differences between FFQ and WFR regressed on personal characteristics were
      significantly associated with at least 1 characteristic for 20 of the 37 foods.
      Sex was significantly associated with differences for 17 food groups, including 5
      specific vegetable groups and 2 "total" fruit and vegetable groups. Use of
      dietary supplements and the presence of a medical condition were associated with
      differences for 5 foods; age, school leaving age, and occupation were associated
      with differences for 1-3 foods. BMI was not associated with differences for any
      foods. Regression models explained from 3% (whole-meal bread) to 37% (for all
      cereals and products) of variation in differences between methods. We conclude
      that the relative validity of intake estimates obtained by FFQ is different for
      men and women for a large number of foods. These results highlight the need for
      appropriate adjustment of diet-disease relations for factors affecting the
      validity of food intake estimates.

PMID- 16424129
TI  - Diet quality is associated with the risk of estrogen receptor-negative breast
      cancer in postmenopausal women.
AB  - Emerging evidence suggests that diet quality indices may serve as prognostic
      indicators of disease. However, the ability of these indices to predict breast
      cancer risk has not been evaluated previously. We assessed the association
      between several diet quality scores and the risk of breast cancer in
      postmenopausal women. The indices we used were the Healthy Eating Index (HEI),
      Alternate Healthy Eating Index (AHEI), Diet Quality Index-Revised (DQI-R),
      Recommended Food Score (RFS), and the alternate Mediterranean Diet Score (aMed).
      We calculated diet quality indices from dietary information collected in FFQ
      administered 5 times between 1984 and 1998 among women in the Nurses' Health
      Study cohort. Relative risks (RR) were computed using Cox proportional hazards
      models and adjusted for known risk factors for breast cancer. Separate analyses
      were conducted for estrogen receptor positive (ER+) and negative (ER-) tumors.
      Between 1984 and 2002, we documented 3,580 cases of breast cancer, of which 2,367
      were ER+, and 575 were ER-. We did not observe any association between the diet
      quality indices and total or ER+ breast cancer risk. However, for ER- breast
      cancer, after adjusting for potential confounders, the RR comparing highest to
      lowest quintiles were 0.78 (95% CI=0.59-1.04, P for trend=0.01) for the AHEI,
      0.69 (95% CI=0.51-0.94, P for trend=0.003) for the RFS, and 0.79 (95% CI=0.60
      1.03, P for trend=0.03) for the aMed. These observations appeared to be the
      result of an inverse association (P for trend=0.01) with the vegetable component
      of the scores. We conclude that women who scored high in AHEI, RFS, and aMed had
      a lower risk of ER- breast cancer. The HEI and DQI-R appeared to be of limited
      value in predicting breast cancer risk.

PMID- 16424130
TI  - Early life factors are determinants of female height at age 19 years in a
      population-based birth cohort (Pelotas, Brazil).
AB  - The purpose of this study was to investigate the influence of biological and
      social background on height of adolescent girls at age 19 y in the city of
      Pelotas, Southern Brazil. In 2001, a sample of the urban census tracts was
      visited and adolescent girls who were part of the Pelotas 1982 Birth Cohort Study
      were located. Standardized questionnaires were administered to the adolescents
      and their mothers. Height was measured using locally manufactured stadiometers;
      standardized protocols were employed. The information obtained in 2001 was
      combined with data collected in earlier phases of the study. The follow-up rate
      was 69% and 473 girls were studied in 2001. Multiple linear regressions were used
      to analyze the determinants of height. The height of the 19-y-old adolescents was
      161.2+/-6.3 cm. The significant determinants of height were family income,
      maternal pre-gestational weight, maternal height, smoking during pregnancy, birth
      weight, height gain, and age at menarche. Birth weight was a more important
      predictor than weight gain during infancy or height gain between the ages of 2
      and 4 y. Each 100 g in birth weight was associated with an increase of
      approximately 0.2 cm in the adolescent's height (P=0.001). The current findings
      reinforce the importance of early life factors in the determination of adult
      height.

PMID- 16424131
TI  - Correction for errors in measuring adherence to prenatal multivitamin/mineral
      supplement use among low-income women.
AB  - Adherence to prenatal multivitamin/mineral supplement use is often measured by
      self-reports or pill counts. Although both measures were shown to overestimate
      adherence, measurement error is rarely considered. In this study, we examined
      measurement error in adherence to prenatal supplement use among pregnant women
      and demonstrated a calibration method to adjust for error. In a validation
      subsample (n=51) from a larger clinical study of supplementation, adherence was
      assessed by self-reports, pill counts, and a Medication Event Monitoring System
      (MEMS) bottle cap that recorded the date and time of each opening of the pill
      bottle. Mean adherence in the validation sample as measured by the MEMS (the gold
      standard) was 68%; thus, adherence measured by self-report (77%) and pill count
      (84%) reflected overestimation. The Pearson correlation coefficients of self
      reports and pill counts to MEMS were 0.35 and 0.62, respectively. When adherence
      was defined as taking >or=75% of the pills prescribed, sensitivity and
      specificity were greater for pill counts (93 and 52%, respectively) than for self
      reports (88 and 44%). The regression coefficient for pill count adherence from a
      linear regression on MEMS adherence was applied to pill counts from a larger
      sample (n=244). The adjustment significantly lowered the estimate of adherence
      from 74 to 64% (P<0.001) in this larger sample. In conclusion, our data show that
      both self-reports and pill counts overestimate adherence and that linear
      regression in comparison to an external standard such as MEMS can be used to
      correct for measurement error in adherence.

PMID- 16424132
TI  - Introduction to the workshop proceedings. Understanding tolerable upper intake
      levels.

PMID- 16424133
TI  - Setting tolerable upper intake levels for nutrients.
AB  - This paper is intended to present the background and general principles embodied
      in the model for the risk assessment of nutrients of the Food and Nutrition Board
      (FNB) of the Institute of Medicine, National Academies. Because no one had
      previously developed a comprehensive approach to the risk assessment of
      nutrients, the FNB Subcommittee on Upper Reference Levels of Nutrients first
      looked at various options that could be used to accomplish this task. During
      initial meetings, the committee considered a variety of options for setting
      tolerable upper intake levels and settled on the risk assessment approach
      described in this paper.

PMID- 16424134
TI  - Toxicology of micronutrients: adverse effects and uncertainty.
AB  - The establishment of safe upper intake levels for micronutrients must consider
      the intake-response relations for both deficiency and toxicity. Limited data are
      available on the toxicities of most micronutrients, and few studies that meet the
      criteria considered essential for the risk assessment of other chemicals in food,
      such as pesticides and food additives, have been performed. In some cases, the
      application of large uncertainty factors, which are used to establish the amount
      of a chemical that would be safe for daily intake throughout life, could result
      in nutritionally inadequate intakes of micronutrients. As a consequence, lower
      than normal uncertainty factors have been applied to determine safe or tolerable
      intakes of many micronutrients. There is no clear scientific rationale, on the
      basis of the metabolism and elimination of micronutrients or the nature of the
      adverse effects reported for high intakes, for the use of reduced uncertainty
      factors for micronutrient toxicity. A review of recent evaluations of selected
      vitamins and minerals shows little consistency in the application of uncertainty
      factors by different advisory groups, such as the Institute of Medicine in the
      United States and the Scientific Committee on Foods in the European Union. It is
      apparent that, in some cases, the uncertainty factor applied was selected largely
      to give a result that is compatible with nutritional requirements; therefore, the
      uncertainty factor represented part of risk management rather than hazard
      characterization. The usual risk assessment procedures for chemicals in food
      should be revised for micronutrients, so that the risks associated with intakes
      that are too low and too high are considered equally as part of a risk-benefit
      analysis.

PMID- 16424135
TI  - A critical assessment of the upper intake levels for infants and children.
AB  - The dietary reference intake (DRI) committees of the Food and Nutrition Board of
      the Institute of Medicine were charged with establishing DRIs for all of the
      essential nutrients, including fat and energy. These reference values are
      quantitative estimates of the nutrient intakes to be used to plan and assess the
      diets of healthy people. The reference values include both recommended intakes
      and tolerable upper intake levels (ULs). The ULs are defined as "the highest
      level of daily nutrient intake that is likely to pose no risk of adverse health
      effects to almost all individuals in the general population." As intake increases
      above the UL, the risk of adverse effects increases. The term "tolerable intake"
      was chosen to avoid the implication of a possible beneficial effect. Instead, the
      term is intended to connote a level of intake that can, with a high probability,
      be tolerated biologically. Yet, with intakes above the ULs, the risk of adverse
      health effects increases. Thus, there is no obvious benefit for healthy
      individuals to consume quantities of nutrients above the UL.

PMID- 16424136
TI  - Evaluation of dietary intake data using the tolerable upper intake levels.
AB  - We discuss the problem of assessing nutrient intake relative to the tolerable
      upper intake levels (UL) for the nutrient proposed by the Institute of Medicine
      and focus on 2 important topics: the estimation of usual nutrient intake
      distributions and the extent to which intakes above the UL can be considered
      risky. With the information that is currently available for most nutrients, it is
      not possible to estimate the proportion of individuals in a group with intakes
      that place them at risk. This is because the shape of the dose-response curve
      needed to carry out a risk assessment is unknown for most nutrients. Thus,
      intakes above UL cannot be declared to be unsafe. Intakes below the UL, however,
      are likely to pose no risk to individuals in the group. Because determining the
      proportion of individuals with intakes below the UL requires estimation of an
      upper-tail percentile of the intake distribution, the use of 1-d intake data or
      otherwise unadjusted intake data are likely to lead to severely biased estimates.
      It is important to remove within-individual variance in intakes from daily
      intakes so that the tails of the usual intake distribution are accurately
      estimated. Underreporting of the amount of nutrients consumed will tend to shift
      the estimated usual nutrient intake distribution downwards. In this case, the
      true proportion of individuals with intakes below the UL is likely to be
      overestimated.

PMID- 16424137
TI  - Gap analysis guidelines for assessing acute, chronic, and lifetime exposures to
      high levels of various nutrients.
AB  - Twenty-two tolerable upper intake levels (ULs) have been established using data
      available from research with both humans and animals. No ULs were established for
      another 10 nutrients for which the existing data were evaluated. Gaps in
      knowledge on the adverse health effects that may arise as a result of acute,
      chronic, and lifetime exposures to high levels of many of these nutrients remain.
      The existence of a UL for a nutrient is not an indication that no gaps in the
      desired information exist, nor does the absence of a UL suggest that no risk of
      adverse health effects exists for very high levels of nutrient intake. Finally,
      it is important to keep in mind the definition of a UL. It is "the highest level
      of daily nutrient intake that is likely to pose no risk of adverse health effects
      for almost all individuals in the general population." There are many gaps in
      knowledge about the levels at which several nutrients cause adverse health
      effects. As these gaps are filled, the values for ULs will be adjusted as
      appropriate.

PMID- 16424138
TI  - Overall discussion: gaps and suggestions. Understanding tolerable upper intake
      levels.

PMID- 16424139
TI  - Introduction to symposium on branched-chain amino acids in exercise.

PMID- 16424140
TI  - Skeletal muscle protein metabolism and resistance exercise.
AB  - Stable isotope tracer techniques have been developed to quantify rates of muscle
      protein synthesis and breakdown in human subjects. These methods were applied to
      the study of the response to resistance exercise as well as to amino acid intake.
      The fractional synthetic rate (FSR) of muscle protein is stimulated for as long
      as 48 h following exercise. However, the anabolic effect of the stimulation of
      FSR after exercise is blunted by a simultaneous increase in muscle protein
      breakdown, such that the net balance between synthesis and breakdown remains
      negative in the fasted state. Elevation of plasma amino acids stimulates muscle
      protein synthesis. The extent of the stimulation is dependent on the dose, the
      profile of amino acids given, the pattern of ingestion (bolus vs. constant
      intake), the age of the subject, and the hormonal profile. Importantly, there is
      an interactive effect between resistance exercise and amino acids, such that the
      net anabolic response to amino acids following exercise is greater than the sum
      of the amino acid effects and the exercise effects alone.

PMID- 16424141
TI  - Nutraceutical effects of branched-chain amino acids on skeletal muscle.
AB  - BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto
      acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA
      catabolic pathway. The activity of the BCKDH complex is regulated by a
      phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal
      muscle under normal and resting conditions is in an inactive/phosphorylated
      state, which may contribute to muscle protein synthesis and muscle growth.
      Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA
      catabolism. Therefore, exercise may increase the BCAA requirement. It has been
      reported that BCAA supplementation before exercise attenuates the breakdown of
      muscle proteins during exercise in humans and that leucine strongly promotes
      protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA
      supplement may attenuate muscle damage induced by exercise and promote recovery
      from the damage. We have examined the effects of BCAA supplementation on delayed
      onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in
      humans. The results obtained showed that BCAA supplementation prior to squat
      exercise decreased DOMS and muscle fatigue occurring for a few days after
      exercise. These findings suggest that BCAAs may be useful for muscle recovery
      following exercise.

PMID- 16424142
TI  - Leucine regulates translation initiation of protein synthesis in skeletal muscle
      after exercise.
AB  - High-performance physical activity and postexercise recovery lead to significant
      changes in amino acid and protein metabolism in skeletal muscle. Central to these
      changes is an increase in the metabolism of the BCAA leucine. During exercise,
      muscle protein synthesis decreases together with a net increase in protein
      degradation and stimulation of BCAA oxidation. The decrease in protein synthesis
      is associated with inhibition of translation initiation factors 4E and 4G and
      ribosomal protein S6 under regulatory controls of intracellular insulin signaling
      and leucine concentrations. BCAA oxidation increases through activation of the
      branched-chain alpha-keto acid dehydrogenase (BCKDH). BCKDH activity increases
      with exercise, reducing plasma and intracellular leucine concentrations. After
      exercise, recovery of muscle protein synthesis requires dietary protein or BCAA
      to increase tissue levels of leucine in order to release the inhibition of the
      initiation factor 4 complex through activation of the protein kinase mammalian
      target of rapamycin (mTOR). Leucine's effect on mTOR is synergistic with insulin
      via the phosphoinositol 3-kinase signaling pathway. Together, insulin and leucine
      allow skeletal muscle to coordinate protein synthesis with physiological state
      and dietary intake.

PMID- 16424143
TI  - Amino acid mixture improves training efficiency in athletes.
AB  - This review discusses some of the beneficial effects of a dietary amino acid
      supplement on muscle function, fatigue, and recovery in exercising athletes. The
      supplement, a mixture of amino acids that included the branched-chain amino
      acids, arginine and glutamine, was studied chronically at several daily dose
      levels for extended periods of time (10, 30, and 90 d). Outcome variables
      included physical measures of muscle strength, fatigue and damage, and blood
      indices of muscle damage and oxygen-carrying capacity. One beneficial effect of
      the amino acid supplement was a quicker recovery from the muscle fatigue that
      followed eccentric exercise training. A dose-response study of the amino acid
      mixture at 2.2, 4.4, and 6.6 g/d for 1 mo showed that at the highest dose,
      indices of blood oxygen-carrying capacity were increased and those of muscle
      damage were decreased at the end of the trial. When the amino acid mixture was
      given for 90 d to elite rugby players during training at a dose of 7.2 g/d, a
      blood-component analysis indicated improvements in the oxygen-carrying capacity
      of the blood. Together, the studies suggest that the amino acid supplement
      contributed to an improvement in training efficiency through positive effects on
      muscle integrity and hematopoiesis.

PMID- 16424144
TI  - A role for branched-chain amino acids in reducing central fatigue.
AB  - Several factors have been identified to cause peripheral fatigue during exercise,
      whereas the mechanisms behind central fatigue are less well known. Changes in the
      brain 5-hydroxytryptamine (5-HT) level is one factor that has been suggested to
      cause fatigue. The rate-limiting step in the synthesis of 5-HT is the transport
      of tryptophan across the blood-brain barrier. This transport is influenced by the
      fraction of tryptophan available for transport into the brain and the
      concentration of the other large neutral amino acids, including the BCAAs
      (leucine, isoleucine, and valine), which are transported via the same carrier
      system. Studies in human subjects have shown that the plasma ratio of free
      tryptophan (unbound to albumin)/BCAAs increases and that tryptophan is taken up
      by the brain during endurance exercise, suggesting that this may increase the
      synthesis of 5-HT in the brain. Ingestion of BCAAs increases their concentration
      in plasma. This may reduce the uptake of tryptophan by the brain and also 5-HT
      synthesis and thereby delay fatigue. Accordingly, when BCAAs were supplied to
      human subjects during a standardized cycle ergometer exercise their ratings of
      perceived exertion and mental fatigue were reduced, and, during a competitive 30
      km cross-country race, their performance on different cognitive tests was
      improved after the race. In some situations the intake of BCAAs also improves
      physical performance. The results also suggest that ingestion of carbohydrates
      during exercise delays a possible effect of BCAAs on fatigue since the brain's
      uptake of tryptophan is reduced.

PMID- 16424145
TI  - Exercise-dependent preference for a mixture of branched-chain amino acids and
      homeostatic control of brain serotonin in exercising rats.
AB  - In this article we discuss studies showing that rats are able to regulate their
      intake of BCAA depending on the level of exercise, and that they will choose a
      solution of BCAA over water during times of intense exercise. We found that the
      voluntary intake of a solution made of BCAA, L-arginine and L-glutamine
      positively correlated with the timing and volume of exercise during the dark
      (active) period of the circadian rhythm. In the second behavioral protocol in
      which rats were fed BCAA fortified diet (2.0%, wt:wt), we observed voluntarily
      increased volume of physical activity beginning from d 4 of feeding on. In the
      second, neuro-behavioral, part of the study we measured the brain content of 5
      hydroxytryptamine (5-HT) as well as plasma amino acid profiles in well-trained
      exercising rats to test a hypothesis that BCAA may alleviate central aspects of
      fatigue. A solution made of BCAA, L-arginine, and L-glutamine applied before
      running elevated the BCAA/tryptophan plasma ratio at the end of and after
      running, and decreased 5-HT release in the lateral hypothalamus and amygdala
      after running, when compared with the controls. The exercise-related shift in the
      fluid preference toward a BCAA-based solution suggests an ergogenic benefit. The
      forced-running study shows the lateral hypothalamus and possibly amygdala might
      be the critical brain regions implied in the central effects of a BCAA-based
      solution.

PMID- 16424146
TI  - Exercise, serum free tryptophan, and central fatigue.
AB  - Brain tryptophan (TRP) concentrations and serotonin (5HT) synthesis and release
      increase during running. This increase in 5HT function may promote central
      fatigue and contribute to suboptimal physical performance. The rise in brain TRP
      is reputed to result from exercise-induced elevations in serum nonesterified
      fatty acid (NEFA) concentrations, which dissociate TRP from albumin in blood and
      increase the serum free TRP pool. But, as discussed in this article, ample
      evidence exists that the serum free TRP pool does not control brain TRP uptake.
      The clearest data are dietary, but pharmacologic data in exercising rats also
      support this conclusion. Changes in the serum levels of amino acids that compete
      with TRP for brain uptake appear also not to explain the rise in brain TRP. The
      mechanism is therefore not presently known. The link between the rise in brain
      TRP and 5HT synthesis/release is not simple: a rise in brain TRP stimulates 5HT
      synthesis/release in actively firing neurons. Hence, during exercise, only 5HT
      neurons that are firing should increase 5HT production/release when brain TRP
      rises. It is not known which 5HT neurons fire during exercise; the 5HT neurons
      that respond to exercise-induced increases in brain TRP are therefore not known.
      Hence, it is not possible to conclude which 5HT neurons contribute to the
      generation of central fatigue. Because some 5HT neurons control specific
      functions important to physical performance (e.g., respiration), the current
      understanding of 5HT neuronal function in central fatigue might benefit from the
      study of specific 5HT pathways during exercise.

PMID- 16424147
TI  - Nevirapine uptake into the central nervous system of the Guinea pig: an in situ
      brain perfusion study.
AB  - The presence of human immunodeficiency virus (HIV) in the central nervous system
      (CNS) is associated with the development of HIV-1-associated dementia (HAD), a
      major cause of HIV-related mortality. To eradicate HIV in the CNS, anti-HIV drugs
      need to reach the brain and cerebrospinal fluid (CSF) in therapeutic
      concentrations. This involves passage through the blood-brain and blood-CSF
      barriers. Using a well established guinea pig in situ brain perfusion model, this
      study investigated whether nevirapine [6H-dipyrido(3,2-b:2',3'-e)(1,4)diazepin-6
      one,11-cyclopropyl-5,11-dihydro-4-methyl], a non-nucleoside reverse transcriptase
      inhibitor (NNRTI), could effectively accumulate in the CNS. [(3)H]Nevirapine was
      coperfused with [(14)C]mannitol (a vascular/paracellular permeability marker)
      through the carotid arteries for up to 30 min, and accumulation in the brain,
      CSF, and choroid plexus was measured. [(3)H]Nevirapine uptake into the cerebrum
      was greater than uptake of [(14)C]mannitol, indicating significant passage across
      the blood-brain barrier and accumulation into the brain (this was further
      confirmed with capillary depletion and high-performance liquid chromatography
      analyses). Likewise, [(3)H]nevirapine showed a great ability to cross the blood
      CSF barrier and accumulate in the CSF, compared with [(14)C]mannitol. The CNS
      accumulation of [(3)H]nevirapine was unaffected by 100 muM nevirapine, suggesting
      that passage across the blood-brain barrier can occur by diffusion. Furthermore,
      coperfusion with 100 muM efavirenz [2H-3,1-benzoxazin-2-one, 6-chloro-4
      (cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-, (4S)-; another NNRTI] did
      not significantly alter CNS accumulation of [(3)H]nevirapine, indicating that the
      efficacy of nevirapine in the CNS would not be altered by the addition of this
      drug to a combination therapy. Together, these data indicate that this anti-HIV
      drug should be beneficial in the eradication of HIV within the CNS and the
      subsequent treatment of HAD.

PMID- 16424148
TI  - Platelet aggregation-induced by caco-2 cells: regulation by matrix
      metalloproteinase-2 and adenosine diphosphate.
AB  - Formation of tumor cell-platelet aggregates facilitates hematogenous metastases.
      However, molecular mechanisms implicated in tumor cell-induced platelet
      aggregation (TCIPA) in colon cancer are unclear. To investigate mechanisms of
      TCIPA induced by colon adenocarcinoma cells in vitro, human Caco-2 cells were
      used to study their interactions with platelets using aggregometry, zymography,
      phase-contrast microscopy, and flow cytometry. Caco-2-induced platelet
      aggregation in a concentration-dependent manner. This aggregation resulted in the
      release of matrix metalloproteinase (MMP)-2, as measured by zymography. In
      addition, flow cytometry showed a significant up-regulation of activated
      GpIIb/IIIa, total GpIIb/IIIa, GpIb, and P-selectin receptors on platelets.
      Inhibition of MMP-2 by phenantroline and degradation of ADP by APT102,
      respectively, resulted in inhibition of TCIPA. Furthermore, both phenantroline
      and APT102 significantly down-regulated the surface abundance of platelet
      receptors. Caco-2 cells aggregate platelets, at least in part, via releasing MMP
      2 and ADP. Modulation of MMP-2 and ADP actions could have therapeutic value in
      colonic cancer.

PMID- 16424149
TI  - Rescue of DeltaF508-CFTR (cystic fibrosis transmembrane conductance regulator) by
      curcumin: involvement of the keratin 18 network.
AB  - The most common mutation in the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene, DeltaF508, causes retention of DeltaF508-CFTR in the
      endoplasmic reticulum and leads to the absence of CFTR Cl(-) channels in the
      plasma membrane. DeltaF508-CFTR retains some Cl(-) channel activity so increased
      expression of DeltaF508-CFTR in the plasma membrane can restore Cl(-) secretion
      deficiency. Recently, curcumin was shown to rescue DeltaF508-CFTR localization
      and function. In our previous work, the keratin 18 (K18) network was implicated
      in DeltaF508-CFTR trafficking. Here, we hypothesized that curcumin could restore
      a functional DeltaF508-CFTR to the plasma membrane acting via the K18 network.
      First, we analyzed the effects of curcumin on the localization of DeltaF508-CFTR
      in different cell lines (HeLa cells stably transfected with wild-type CFTR or
      DeltaF508-CFTR, CALU-3 cells, or cystic fibrosis pancreatic epithelial cells
      CFPAC-1) and found that it was significantly delocalized toward the plasma
      membrane in DeltaF508-CFTR-expressing cells. We also performed a functional assay
      for the CFTR chloride channel in CFPAC-1 cells treated or not with curcumin and
      detected an increase in a cAMP-dependent chloride efflux in treated DeltaF508
      CFTR-expressing cells. The K18 network then was analyzed by immunocytochemistry
      and immunoblot exclusively in curcumin-treated or untreated CFPAC-1 cells because
      of their endogenic DeltaF508-CFTR expression. After curcumin treatment, we
      observed a remodeling of the K18 network and a significant increase in K18 Ser52
      phosphorylation, a site directly implicated in the reorganization of intermediate
      filaments. With these results, we propose that K18 as a new therapeutic target
      and curcumin, and/or its analogs, might be considered as potential therapeutic
      agents for cystic fibrosis.

PMID- 16424150
TI  - In vitro metabolism of (nitrooxy)butyl ester nitric oxide-releasing compounds:
      comparison with glyceryl trinitrate.
AB  - We investigated the in vitro metabolism of two (nitrooxy)butyl ester nitric oxide
      (NO) donor derivatives of flurbiprofen and ferulic acid, [1,1'-biphenyl]-4-acetic
      acid-2-fluoro-alpha-methyl-4-(nitrooxy)butyl ester (HCT 1026) and 3-(4-hydroxy-3
      methoxyphenyl)-2-propenoic acid 4-(nitrooxy)butyl ester (NCX 2057), respectively,
      in rat blood plasma and liver subcellular fractions compared with (nitrooxy)butyl
      alcohol (NOBA) and glyceryl trinitrate (GTN). HCT 1026 and NCX 2057 undergo rapid
      ubiquitous carboxyl ester hydrolysis to their respective parent compounds and
      NOBA. The nitrate moiety of this latter is subsequently metabolized to inorganic
      nitrogen oxides (NOx), predominantly in liver cytosol by glutathione S
      transferase (GST) and to a lesser extent in liver mitochondria. If, however, in
      liver cytosol, the carboxyl ester hydrolysis is prevented by an esterase
      inhibitor, the metabolism at the nitrate moiety level does not occur. In blood
      plasma, HCT 1026 and NCX 2057 are not metabolized to NOx, whereas a slow but
      sustained NO generation in deoxygenated whole blood as detected by electron
      paramagnetic resonance indicates the involvement of erythrocytes in the
      bioactivation of these compounds. Differently from NOBA, GTN is also metabolized
      in blood plasma and more quickly metabolized by different GST isoforms in liver
      cytosol. The cytosolic GST-mediated denitration of these organic nitrates in
      liver limits their interaction with other intracellular compartments to possible
      generation of NO and/or their subsequent availability and bioactivation in the
      systemic circulation and extrahepatic tissues. We show the possibility of
      modulating the activity of hepatic cytosolic enzymes involved in the metabolism
      of (nitrooxy)butyl ester compounds, thus increasing the therapeutic potential of
      this class of compounds.

PMID- 16424151
TI  - The gene of retroviral origin Syncytin 1 is specific to hominoids and is inactive
      in Old World monkeys.
AB  - Syncytin 1 is one of the best known examples of recent acquisition of a new gene
      from an endogenous retrovirus (HERV) in the human genome and has been implicated
      in placental physiology. Within primates, Syncytin 1 is conserved in all
      hominoids but has not been characterized in Old World monkeys (OWMs). In this
      study, we investigated the status of Syncytin 1 in 14 hominoid and OWM species.
      We show that although the HERV-W provirus responsible for the origin of this gene
      was present in the genome of the most recent common ancestor of hominoids and
      OWMs, Syncytin 1 is inactive in OWMs. In addition, we were able to determine that
      the evolution of Syncytin 1 in hominoids involved an accumulation of amino acid
      changes and showed signatures of both positive and purifying selection. Our
      results indicate that Syncytin 1 is indeed a hominoid-specific gene and
      illustrate the complex and dynamic process associated with the origin of new
      genes.

PMID- 16424152
TI  - In the beginning was Sm.

PMID- 16424154
TI  - The central role of the alternative complement pathway in human disease.
AB  - The complement system is increasingly recognized as important in the pathogenesis
      of tissue injury in vivo following immune, ischemic, or infectious insults.
      Within the complement system, three pathways are capable of initiating the
      processes that result in C3 activation: classical, alternative, and lectin.
      Although the roles that proinflammatory peptides and complexes generated during
      complement activation play in mediating disease processes have been studied
      extensively, the relative contributions of the three activating pathways is less
      well understood. Herein we examine recent evidence that the alternative
      complement pathway plays a key and, in most instances, obligate role in
      generating proinflammatory complement activation products in vivo. In addition,
      we discuss new concepts regarding the mechanisms by which the alternative pathway
      is activated in vivo, as recent clinical findings and experimental results have
      provided evidence that continuous active control of this pathway is necessary to
      prevent unintended targeting and injury to self tissues.

PMID- 16424153
TI  - Characteristics of a soluble nuclear antigen precipitating with sera of patients
      with systemic lupus erythematosus. J. Immunol. 1966. 96: 464-471.

PMID- 16424155
TI  - Cutting edge: identification of E-cadherin as a ligand for the murine killer cell
      lectin-like receptor G1.
AB  - The killer cell lectin-like receptor G1 (KLRG1) is expressed by NK cells and by T
      cells. In both humans and mice, KLRG1 identifies Ag-experienced T cells that are
      impaired in their proliferative capacity but are capable of performing effector
      functions. In this study, we identified E-cadherin as a ligand for murine KLRG1
      by using fluorescently labeled, soluble tetrameric complexes of the extracellular
      domain of the murine KLRG1 molecule as staining reagents in expression cloning.
      Ectopic expression of E-cadherin in B16.BL6 target cells did not affect cell
      mediated lysis by lymphokine-activated NK cells and by CD8 T cells but inhibited
      Ag-induced proliferation and induction of cytolytic activity of CD8 T cells. E
      cadherin is expressed by normal epithelial cells, Langerhans cells, and
      keratinocytes and is usually down-regulated on metastatic cancer cells. KLRG1
      ligation by E-cadherin in healthy tissue may thus exert an inhibitory effect on
      primed T cells.

PMID- 16424156
TI  - Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a
      multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo.
AB  - Mice deficient in the E3 ubiquitin ligase Cbl-b have CD28-independent T cells and
      develop autoimmunity. We previously reported that Cbl-b-/- CD4+CD25- T effector
      cells are resistant in vitro to the antiproliferative effects of CD4+CD25+
      regulatory T cells and TGF-beta. We have now asked whether the resistance noted
      in Cbl-b-/- T cells is restricted solely to TGF-beta's antiproliferative effects,
      whether the TGF-beta resistance has in vivo relevance, and whether a defect can
      be identified in the TGF-beta signaling pathway. We now demonstrate the
      following: 1) in vitro, Cbl-b deficiency prevents the TGF-beta-mediated induction
      of Foxp3+ functional regulatory T cells; 2) in vivo, Cbl-b-/- mice show a
      significantly enhanced response to a tumor that is strictly TGF-beta regulated;
      and 3) Cbl-b-/- T effector cells have defective TGF-beta-mediated Smad2
      phosphorylation. These studies are the first to document that the E3 ubiquitin
      ligase Cbl-b plays an integral role in T cell TGF-beta signaling, and that its
      absence results in multifunctional TGF-beta-related defects that have important
      disease-related implications.

PMID- 16424158
TI  - Cutting edge: prostaglandin D2 enhances leukotriene C4 synthesis by eosinophils
      during allergic inflammation: synergistic in vivo role of endogenous eotaxin.
AB  - In addition to the well-recognized ability of prostaglandin D2 (PGD2) to regulate
      eosinophil trafficking, we asked whether PGD2 was also able to activate
      eosinophils and control their leukotriene C4 (LTC4)-synthesizing machinery. PGD2
      administration to presensitized mice enhanced in vivo LTC4 production and
      formation of eosinophil lipid bodies-potential LTC4-synthesizing organelles.
      Immunolocalization of newly formed LTC4 demonstrated that eosinophil lipid bodies
      were the sites of LTC4 synthesis during PGD2-induced eosinophilic inflammation.
      Pretreatment with HQL-79, an inhibitor of PGD synthase, abolished LTC4 synthesis
      and eosinophil lipid body formation triggered by allergic challenge. Although
      PGD2 was able to directly activate eosinophils in vitro, in vivo PGD2-induced
      lipid body-driven LTC4 synthesis within eosinophils was dependent on the
      synergistic activity of endogenous eotaxin acting via CCR3. Our findings, that
      PGD2 activated eosinophils and enhanced LTC4 synthesis in vivo in addition to the
      established PGD2 roles in eosinophil recruitment, heighten the interest in PGD2
      as a target for antiallergic therapies.

PMID- 16424157
TI  - Cutting edge: a novel nonoxidative phagosomal mechanism exerted by cathepsin-D
      controls Listeria monocytogenes intracellular growth.
AB  - Deciphering how Listeria monocytogenes exploits the host cell machinery to invade
      mammalian cells is a key issue in understanding the pathogenesis of this food
      borne pathogen, which can cause diseases ranging from gastroenteritis to
      meningitis and abortion. In this study, we show that the lysosomal aspartyl
      protease cathepsin-D (Ctsd) is of considerable importance for nonoxidative
      listericidal defense mechanisms. We observed enhanced susceptibility to L.
      monocytogenes infection of fibroblasts and bone-marrow macrophages and increased
      intraphagosomal viability of bacteria in fibroblasts isolated from Ctsd-deficient
      mice compared with wild type. These findings are further supported by prolonged
      survival of L. monocytogenes in Ctsd-deficient mice after infection. Transient
      transfection of Ctsd in wild-type cells was sufficient to revert these wild-type
      phagosomes back to microbicidal compartments. Based on infection experiments with
      mutant bacteria, in vitro degradation, and immunoprecipitation experiments, we
      suggest that a major target of cathepsin D is the main virulence factor
      listeriolysin O.

PMID- 16424159
TI  - Soluble HLA-G inhibits cell cycle progression in human alloreactive T
      lymphocytes.
AB  - HLA-G is involved in regulating T cell responses. Various mechanisms have been
      proposed to explain the inhibition of T cell proliferation. In this context, the
      possible role of HLA-G in cell cycle regulation remains to be explored. Using
      stably transfected M8 cells expressing the secreted isoform (HLA-G5) of HLA-G, we
      investigated the role of HLA-G in inducing apoptosis and in controlling the cell
      cycle of activated T cells. Soluble HLA-G (HLA-G5) inhibited both CD4 and CD8 T
      cell proliferation. However, HLA-G5 did not induce T cell apoptosis, as
      determined by 3,3'-diethyloxacarbocyanine and propidium iodine labeling. It
      induced accumulation of the retinoblastoma protein, but not its phosphorylated
      and active form. Treatment of activated T cells with HLA-G5 also reduced the
      amounts of cyclin D2, E, A, and B by >80%. In contrast, it induced an
      accumulation of p27kip, but not p21cip, in activated T cells. HLA-G does not
      induce apoptosis of alloreactive T cells, but induces p27kip1 and inhibits cell
      cycle progression.

PMID- 16424160
TI  - The endoplasmic reticulum is a key component of the plasma cell death pathway.
AB  - Plasma cells (PC) are the effector cells of the humoral Ab response. Unlike other
      dedicated secretory cells, they exist as two populations with opposite cell
      fates: short-lived and long-lived PC. Upon transformation they lead to an
      incurable neoplasia called multiple myeloma. In this study we have explored the
      molecular mechanism of PC death. Our data show that their apoptotic pathway is
      unique among other hemopoietic cells inasmuch as neither the death receptors nor
      the mitochondria play the central role. PC apoptosis is initiated by activation
      of Bax at the endoplasmic reticulum membrane and subsequent activation of the
      endoplasmic reticulum-associated caspase-4 before the release of mitochondrial
      apoptogenic factors. Together, our observations indicate that the cardinal
      function of PC (i.e., Ig secretion) is also the cause of their death.

PMID- 16424161
TI  - Direct costimulatory effect of TLR3 ligand poly(I:C) on human gamma delta T
      lymphocytes.
AB  - TLR3 recognizes viral dsRNA and its synthetic mimetic polyinosinic-polycytidylic
      acid (poly(I:C)). TLR3 expression is commonly considered to be restricted to
      dendritic cells, NK cells, and fibroblasts. In this study we report that human
      gammadelta and alphabeta T lymphocytes also express TLR3, as shown by
      quantitative real-time PCR, flow cytometry, and confocal microscopy. Although T
      cells did not respond directly to poly(I:C), we observed a dramatic increase in
      IFN-gamma secretion and an up-regulation of CD69 when freshly isolated gammadelta
      T cells were stimulated via TCR in the presence of poly(I:C) without APC. IFN
      gamma secretion was partially inhibited by anti-TLR3 Abs. In contrast, poly(I:C)
      did not costimulate IFN-gamma secretion by alphabeta T cells. These results
      indicate that TLR3 signaling is differentially regulated in TCR-stimulated
      gammadelta and alphabeta T cells, suggesting an early activation of gammadelta T
      cells in antiviral immunity.

PMID- 16424162
TI  - Flightless I homolog negatively modulates the TLR pathway.
AB  - To date, much of our knowledge about the signaling networks involved in the
      innate immune response has come from studies using nonphysiologic model systems
      rather than actual immune cells. In this study, we used a dual-tagging proteomic
      strategy to identify the components of the MyD88 signalosome in murine
      macrophages stimulated with lipid A. This systems approach revealed 16 potential
      MyD88-interacting partners, one of which, flightless I homolog (Fliih) was
      verified to interact with MyD88 and was further characterized as a negative
      regulator of the TLR4-MyD88 pathway. Conversely, a reduction in endogenous Fliih
      by small-interfering RNA enhanced the activation of NF-kappaB, as well as
      cytokine production by LPS. Results from immunoprecipitation and a two-hybrid
      assay further indicated that Fliih directly interfered with the formation of the
      TLR4-MyD88 signaling complex. These results in turn suggest a new basis for the
      regulation of the TLR pathway by Fliih.

PMID- 16424163
TI  - Immunologic control of tumors by in vivo Fc gamma receptor-targeted antigen
      loading in conjunction with double-stranded RNA-mediated immune modulation.
AB  - Despite the expression of non-self or neo-epitopes, many tumors such as lymphoid
      malignancies or cancers induced by oncogenic viruses are able to gradually
      overcome the immune defense mechanisms and spread. Using a preclinical model of
      hematological malignancy, we show that Ig-associated idiotypic determinants are
      recognized by the immune system in a fashion that results in immune deviation,
      allowing tumor progression and establishment of metastases. Using gene-targeted
      mice, we show that anti-idiotypic MHC class I-restricted immunity is promoted by
      ITAM motif (ITAM+) FcgammaR, but kept in check by ITIM motif (ITIM+) FcgammaRIIB
      mediated mechanisms. In addition to interfering with the functionality of ITIM+
      FcgammaR, effective anti-idiotypic and antitumoral immunity can be achieved by
      FcgammaR-targeted delivery of epitope in conjunction with administration of
      stimulatory motifs such as dsRNA, correcting the ineffective response to
      idiotypic epitopes. The immune process initiated by FcgammaR-mediated targeting
      of epitope together with dsRNA, resulted in control of tumor growth,
      establishment of immune memory and protection against tumors bearing antigenic
      variants. In summary, targeted delivery of MHC class I-restricted epitopes via
      ITAM+ FcgammaR, in conjunction with use of TLR-binding immune stimulatory motifs
      such as dsRNA, overcomes suboptimal responses to idiotypic determinants and may
      constitute a novel approach for the treatment of a broad range of malignancies.
      Finally, the results shed light on the mechanisms regulating the idiotypic
      network and managing the diversity associated with immune receptors.

PMID- 16424164
TI  - Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell
      function.
AB  - Many tumor cells shed specialized membrane vesicles known as exosomes. In this
      study, we show that pretreatment of mice with exosomes produced by TS/A or 4T.1
      murine mammary tumor cells resulted in accelerated growth of implanted tumor
      cells in both syngeneic BALB/c mice and nude mice. As implanted TS/A tumor cells
      grew more rapidly in mice that had been depleted of NK cells, we analyzed the
      effects of the tumor-derived exosomes on NK cells. The tumor-derived exosomes
      inhibit NK cell cytotoxic activity ex vivo and in vitro as demonstrated by
      chromium release assays. The treatment of mice with TS/A tumor exosomes also led
      to a reduction in the percentages of NK cells, as determined by FACS analysis, in
      the lungs and spleens. Key features of NK cell activity were inhibited, including
      release of perforin but not granzyme B, as well as the expression of cyclin D3
      and activation of the Jak3-mediated pathways. Human tumor cell lines also were
      found to produce exosomes that were capable of inhibiting IL-2-stimulated NK cell
      proliferation. Exosomes produced by dendritic cells or B cells did not. The
      presentation of tumor Ags by exosomes is under consideration as a cancer vaccine
      strategy; however, we found that pretreatment of mice with tumor exosomes blunted
      the protective effect of syngeneic dendritic cells pulsed ex vivo with tumor
      exosomes. We propose that tumor exosomes contribute to the growth of tumors by
      blocking IL-2-mediated activation of NK cells and their cytotoxic response to
      tumor cells.

PMID- 16424165
TI  - Potentiation of antigen-stimulated V gamma 9V delta 2 T cell cytokine production
      by immature dendritic cells (DC) and reciprocal effect on DC maturation.
AB  - Vgamma9Vdelta2 T cells, a major gammadelta PBL subset in human adults, have been
      previously implicated in dendritic cell (DC) licensing, owing to their high
      frequency in peripheral tissues and their ability to produce inflammatory
      cytokines upon recognition of a broad array of conserved Ags. Although these
      observations implied efficient recognition of Ag-expressing immature DC (iDC) by
      Vgamma9Vdelta2 T cells, the role played by DC subsets in activation of these
      lymphocytes has not been carefully studied so far. We show that iDC, and to a
      lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or
      proliferative responses, of established Vgamma9Vdelta2 T cell clones and ex vivo
      memory Vgamma9Vdelta2 PBL stimulated by synthetic agonists. The ability of iDC to
      potentiate Vgamma9Vdelta2 production of inflammatory cytokines required for their
      own maturation suggested that Vgamma9Vdelta2 T cells, despite their strong lytic
      activity, could promote efficient iDC licensing without killing at suboptimal Ag
      doses. Accordingly Vgamma9Vdelta2 cells induced accelerated maturation of Ag
      expressing iDC but not "bystander" DC, even within mixed cell populations
      comprising both Ag-expressing and nonexpressing iDC. Furthermore Vgamma9Vdelta2
      cells induced full differentiation into IL-12-producing cells of iDC infected by
      Vgamma9Vdelta2-stimulating mycobacteria that were otherwise unable to induce
      complete DC maturation. In conclusion the ability of iDC to selectively
      potentiate cytokine response of memory Vgamma9Vdelta2 T cells could underlie the
      adjuvant effect of these lymphocytes, and possibly other natural memory T cells,
      on conventional T cell responses.

PMID- 16424166
TI  - Critical, but conditional, role of OX40 in memory T cell-mediated rejection.
AB  - Memory T cells can be a significant barrier to the induction of transplant
      tolerance. However, the molecular pathways that can regulate memory T cell
      mediated rejection are poorly defined. In the present study we tested the
      hypothesis that the novel alternative costimulatory molecules (i.e., ICOS, 4-1BB,
      OX40, or CD30) may play a critical role in memory T cell activation and memory T
      cell-mediated rejection. We found that memory T cells, generated by either
      homeostatic proliferation or donor Ag priming, induced prompt skin allograft
      rejection regardless of CD28/CD154 blockade. Phenotypic analysis showed that, in
      contrast to naive T cells, such memory T cells expressed high levels of OX40, 4
      1BB, and ICOS on the cell surface. In a skin transplant model in which rejection
      was mediated by memory T cells, blocking the OX40/OX40 ligand pathway alone did
      not prolong the skin allograft survival, but blocking OX40 costimulation in
      combination with CD28/CD154 blockade induced long-term skin allograft survival,
      and 40% of the recipients accepted their skin allograft for >100 days. In
      contrast, blocking the ICOS/ICOS ligand and the 4-1BB/4-1BBL pathways alone or
      combined with CD28/CD154 blockade had no effect in preventing skin allograft
      rejection. OX40 blockade did not affect the homeostatic proliferation of T cells
      in vivo, but markedly inhibited the effector functions of memory T cells. Our
      data demonstrate that memory T cells resisting to CD28/CD154 blockade in
      transplant rejection are sensitive to OX40 blockade and suggest that OX40 is a
      key therapeutic target in memory T cell-mediated rejection.

PMID- 16424167
TI  - CD40 expression by microglial cells is required for their completion of a two
      step activation process during central nervous system autoimmune inflammation.
AB  - Microglial cells are monocytic lineage cells that reside in the CNS and have the
      capacity to become activated during various pathological conditions. Although it
      was demonstrated that activation of microglial cells could be achieved in vitro
      by the engagement of CD40-CD40L interactions in combination with proinflammatory
      cytokines, the exact factors that mediate activation of microglial cells in vivo
      during CNS autoimmunity are ill-defined. To investigate the role of CD40 in
      microglial cell activation during experimental autoimmune encephalomyelitis
      (EAE), we used bone marrow chimera mice that allowed us to distinguish microglial
      cells from peripheral macrophages and render microglial cells deficient in CD40.
      We found that the first step of microglial cell activation was CD40-independent
      and occurred during EAE onset. The first step of activation consisted of
      microglial cell proliferation and up-regulation of the activation markers MHC
      class II, CD40, and CD86. At the peak of disease, microglial cells underwent a
      second step of activation, which was characterized by a further enhancement in
      activation marker expression along with a reduction in proliferation. The second
      step of microglial cell activation was CD40-dependent and the failure of CD40
      deficient microglial cells to achieve a full level of activation during EAE was
      correlated with reduced expansion of encephalitogenic T cells and leukocyte
      infiltration in the CNS, and amelioration of clinical symptoms. Thus, our
      findings demonstrate that CD40 expression on microglial cells is necessary to
      complete their activation process during EAE, which is important for disease
      progression.

PMID- 16424168
TI  - Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated
      immune response.
AB  - T cell Ig mucin 3 (Tim-3) has been found to play an important role in Th1
      mediated auto- and alloimmune responses, but the function of soluble form of Tim
      3 (sTim-3) remains to be elucidated. In this study, we report the inhibitory
      effect of sTim-3 on T cell-mediated immune response. In this study, sTim-3 mRNA
      was found, among different tissues and organs, only in splenic cells, and the
      activation of splenocytes resulted in up-regulated production of both sTim-3 mRNA
      and protein. We constructed a eukaryotic expression plasmid, psTim-3, which
      expresses functional murine sTim-3. In C57BL/6 mice inoculated with B16F1
      melanoma cells, the growth of tumor was facilitated by the expression of this
      plasmid in vivo. Furthermore, sTim-3 inhibited the responses of T cells to Ag
      specific stimulation or anti-CD3 mAb plus anti-CD28 mAb costimulation and the
      production of cytokines IL-2 and IFN-gamma in vitro. In tumor rejection model,
      sTim-3 significantly impaired T cell antitumor immunity, evidenced by decreased
      antitumor CTL activity and reduced amount of tumor-infiltrating lymphocytes in
      tumor. Real-time PCR analysis of gene expression in tumor microenvironment
      revealed the decreased expression of Th1 cytokine genes and the unchanged profile
      of the genes related to T regulatory cell function, suggesting that the
      inhibitory effect of sTim-3 on the generation of Ag-specific T cells in vivo is
      dominated by T effector cells rather than T regulatory cells. Our studies thus
      define sTim-3 as an immunoregulatory molecule that may be involved in the
      negative regulation of T cell-mediated immune response.

PMID- 16424169
TI  - A cell-type specific CD1d expression program modulates invariant NKT cell
      development and function.
AB  - Invariant NK T (iNKT) cells are a distinct subset of T cells that rapidly produce
      an array of immunoregulatory cytokines upon activation. Cytokines produced by
      iNKT cells subsequently transactivate other leukocytes and elicit their
      respective effector functions. In this way, iNKT cells play a central role in
      coordinating the development of immune responses in a variety of settings.
      However, the mechanisms governing the quality of the iNKT cell response elicited
      remain poorly defined. To address whether changes in the CD1d expression pattern
      could regulate iNKT cell function, we generated a transgenic (Tg) mouse model in
      which thymocytes and peripheral T cells express high levels of CD1d (Lck-CD1d Tg+
      mice). The expression of CD1d by T cells was sufficient to rescue development of
      iNKT cells in mice deficient of endogenous CD1d. However, the relative
      proportions of iNKT cell subsets in Lck-CD1d Tg+ mice were distinctly different
      from those in wild-type mice, suggesting an altered developmental program.
      Additionally, iNKT cells were hyporesponsive to antigenic stimulation in vivo.
      Interestingly, Lck-CD1d Tg+ mice develop liver pathology in the absence of any
      exogenous manipulation. The results of these studies suggest that changes to the
      CD1d expression program modulate iNKT cell development and function.

PMID- 16424170
TI  - Protein expression of TNF-alpha in psoriatic skin is regulated at a
      posttranscriptional level by MAPK-activated protein kinase 2.
AB  - Alterations in specific signal transduction pathways may explain the increased
      expression of proinflammatory cytokines seen in inflammatory diseases such as
      psoriasis. We reveal increased TNF-alpha protein expression, but similar TNF
      alpha mRNA levels, in lesional compared with nonlesional psoriatic skin,
      demonstrating for the first time that TNF-alpha expression in lesional psoriatic
      skin is regulated posttranscriptionally. Increased levels of activated MAPK
      activated protein kinase 2 (MK2) together with increased MK2 kinase activity were
      found in lesional compared with nonlesional psoriatic skin. Immunohistochemical
      analysis showed that activated MK2 was located in the basal layers of the
      psoriatic epidermis, whereas no positive staining was seen in nonlesional
      psoriatic skin. In vitro experiments demonstrated that both anisomycin and IL
      1beta caused a significant activation of p38 MAPK and MK2 in cultured normal
      human keratinocytes. In addition, TNF-alpha protein levels were significantly up
      regulated in keratinocytes stimulated with anisomycin or IL-1beta. This increase
      in TNF-alpha protein expression was completely blocked by the p38 inhibitor,
      SB202190. Transfection of cultured keratinocytes with MK2-specific small
      interfering RNA led to a significant decrease in MK2 expression and a subsequent
      significant reduction in the protein expression of the proinflammatory cytokines
      TNF-alpha, IL-6, and IL-8, whereas no change in the expression of the anti
      inflammatory cytokine IL-10 was seen. This is the first time that MK2 expression
      and activity have been investigated in an inflammatory disease such as psoriasis.
      The results strongly suggest that increased activation of MK2 is responsible for
      the elevated and posttranscriptionally regulated TNF-alpha protein expression in
      psoriatic skin, making MK2 a potential target in the treatment of psoriasis.

PMID- 16424171
TI  - Human naive CD8 T cells down-regulate expression of the WNT pathway transcription
      factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell
      factor-1) following antigen encounter in vitro and in vivo.
AB  - The transcription factors lymphoid enhancer binding factor 1 (LEF1) and
      transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors
      of the WNT signaling pathway, which is a critical regulator of T cell development
      in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only
      expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag
      encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to
      the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T
      cells. We further show that resting T cells preferentially express inhibitory
      LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform
      balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study
      suggests that proteins involved in the WNT signaling pathway not only regulate T
      cell development, but also peripheral T cell differentiation.

PMID- 16424172
TI  - Tumor-specific CD4+ T cells are activated by "cross-dressed" dendritic cells
      presenting peptide-MHC class II complexes acquired from cell-based cancer
      vaccines.
AB  - Tumor cells that constitutively express MHC class I molecules and are genetically
      modified to express MHC class II (MHC II) and costimulatory molecules are
      immunogenic and have therapeutic efficacy against established primary and
      metastatic cancers in syngeneic mice and activate tumor-specific human CD4+ T
      lymphocytes. Previous studies have indicated that these MHC II vaccines enhance
      immunity by directly activating tumor-specific CD4+ T cells during the
      immunization process. Because dendritic cells (DCs) are considered to be the most
      efficient APCs, we have now examined the role of DCs in CD4+ T cell activation by
      the MHC II vaccines. Surprisingly, we find that DCs are essential for MHC II
      vaccine immunogenicity; however, they mediate their effect through "cross
      dressing." Cross-dressing, or peptide-MHC (pMHC) transfer, involves the
      generation of pMHC complexes within the vaccine cells, and their subsequent
      transfer to DCs, which then present the intact, unprocessed complexes to CD4+ T
      lymphocytes. The net result is that DCs are the functional APCs; however, the
      immunogenic pMHC complexes are generated by the tumor cells. Because MHC II
      vaccine cells do not express the MHC II accessory molecules invariant chain and
      DM, they are likely to load additional tumor Ag epitopes onto MHC II molecules
      and therefore activate a different repertoire of T cells than DCs. These data
      further the concept that transfer of cellular material to DCs is important in Ag
      presentation, and they have direct implications for the design of cancer
      vaccines.

PMID- 16424173
TI  - CXCR3/CXCR3 ligand biological axis impairs RENCA tumor growth by a mechanism of
      immunoangiostasis.
AB  - Metastatic renal cell carcinoma (RCC) responds poorly to chemo- or radiation
      therapy but appears to respond to systemic immunotherapy (i.e., IL-2 and/or IFN
      alpha), albeit with only 5-10% durable response. The CXCR3/CXCR3 ligand
      biological axis plays an important role in mediating type 1 cytokine-dependent
      cell-mediated immunity, which could be beneficial for attenuating RCC if
      optimized. We found that systemic IL-2 induced the expression of CXCR3 on
      circulating mononuclear cells but impaired the CXCR3 ligand chemotactic gradient
      from plasma to tumor by increasing circulating CXCR3 ligand levels in a murine
      model of RCC. Moreover, the antitumor effect of systemic IL-2 was CXCR3
      dependent, as IL-2 failed to inhibit tumor growth and angiogenesis in CXCR3-/-
      mice. We hypothesized that the immunotherapeutic effect of the CXCR3/CXCR3 ligand
      biological axis could be optimized by first priming with systemic IL-2 to induce
      CXCR3 expression on circulating mononuclear cells followed by enhancing the
      intratumor CXCR3 ligand levels to establish optimal CXCR3-dependent chemotactic
      gradient. We found that combined systemic IL-2 with an intratumor CXCR3 ligand
      (CXCL9) lead to significantly greater reduction in tumor growth and angiogenesis,
      increased tumor necrosis, and increased intratumor infiltration of CXCR3+
      mononuclear cells, as compared with either IL-2 or CXCL9 alone. The enhanced
      antitumor effect of the combined strategy was associated with a more optimized
      CXCR3-dependent chemotactic gradient and increased tumor-specific immune
      response. These data suggest that the combined strategy of systemic IL-2 with
      intratumor CXCR3 ligand is more efficacious than either strategy alone for
      reducing tumor-associated angiogenesis and augmenting tumor-associated immunity,
      the concept of immunoangiostasis.

PMID- 16424174
TI  - Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells,
      whereas infections induce more IFN-gamma-secreting cells.
AB  - Mouse and human CD4 T cells primed during an immune response may differentiate
      into effector phenotypes such as Th1 (secreting IFN-gamma) or Th2 (secreting IL
      4) that mediate effective immunity against different classes of pathogen.
      However, primed CD4 T cells can also remain uncommitted, secreting IL-2 and
      chemokines, but not IFN-gamma or IL-4. We now show that human CD4 T cells primed
      by protein vaccines mostly secreted IL-2, but not IFN-gamma, whereas in the same
      individuals most CD4 T cells initially primed by infection with live pathogens
      secreted IFN-gamma. We further demonstrate that many tetanus-specific IL-2+IFN
      gamma- cells are uncommitted and that a single IL-2+IFN-gamma- cell can
      differentiate into Th1 or Th2 phenotypes following in vitro stimulation under
      appropriate polarizing conditions. In contrast, influenza-specific IL-2+IFN-gamma
      CD4 cells maintained a Th1-like phenotype even under Th2-polarizing conditions.
      Similarly, adoptively transferred OTII transgenic mouse T cells secreted mainly
      IL-2 after priming with OVA in alum, but were biased toward IFN-gamma secretion
      when primed with the same OVA peptide presented as a pathogen Ag during live
      infection. Thus, protein subunit vaccines may prime a unique subset of
      differentiated, but uncommitted CD4 T cells that lack some of the functional
      properties of committed effectors induced by infection. This has implications for
      the design of more effective vaccines against pathogens requiring strong CD4
      effector T cell responses.

PMID- 16424175
TI  - Enhanced FTY720-mediated lymphocyte homing requires G alpha i signaling and
      depends on beta 2 and beta 7 integrin.
AB  - The immunomodulatory drug FTY720 interferes with sphingosine-1-phosphate (S1P)
      receptor signaling leading to lymphocyte retention in secondary lymphoid organs
      and consequently to profound lymphopenia in the peripheral blood. The molecular
      mechanisms transduced by S1P receptors upon being triggered by its native ligand,
      S1P, or by FTY720, are largely unknown. In this study we analyze the role of
      beta2 and beta7 integrin and their ligands ICAM-1, VCAM-1, and MadCAM-1 on
      lymphocyte homing in the presence of FTY720. We demonstrate that this drug
      facilitates homing of lymphocytes single-deficient of either beta2 or beta7
      integrin but not of beta2-deficient lymphocytes, which in addition were blocked
      by anti-beta7 integrin Abs. Enhanced lymphocyte homing is preceded by increased
      adherence of integrin-deficient as well as wild-type lymphocytes to high
      endothelial venules (HEV) in FTY720-treated animals. Elevated adherence to HEV
      requires intact lymphocyte Galphai signaling that cannot be stably imprinted on
      lymphocytes even after prolonged exposure to FTY720. Thus, FTY720 influences
      lymphocyte homeostasis not only by suppressing lymphocyte egress from lymph nodes
      but also by facilitating lymphocyte homing across HEV in an integrin-dependent
      fashion.

PMID- 16424176
TI  - Splenic dendritic cells induced by oral antigen administration are important for
      the transfer of oral tolerance in an experimental model of asthma.
AB  - Peripheral tolerance can be induced after the feeding of Ag, which is referred to
      as oral tolerance. We demonstrated in this study that the oral administration of
      OVA induced tolerance in an experimental model of asthma in mice, and
      investigated which cells function as the regulatory cells in the transfer of this
      oral tolerance. In OVA-fed mice, the percentage of eosinophils in bronchoalveolar
      lavage fluid, serum IgE levels, airway hyperresponsiveness, and mRNA levels of IL
      13 and eotaxin were significantly lower than found in nonfed mice. Histological
      examination of lung tissue showed a suppression of the accumulation of
      inflammatory cells in the peribronchial area of OVA-fed mice. Feeding after the
      first immunization or between the first and the second immunization suppressed
      these findings, whereas feeding just before the airway Ag challenge did not. The
      suppression of disease in OVA-fed mice was successfully transferred by injection
      of whole spleen cells of OVA-fed mice. When CD11c+ dendritic cells (DCs) were
      removed from splenocytes, this transfer of suppression was completely abolished.
      The injection of splenic DCs purified from OVA-fed mice alone transferred the
      suppression, whereas the injection of splenic DCs from naive mice that were
      cocultured with OVA in vitro did not. These data suggest that not only CD4+ T
      cells, but also CD11c+ DCs induced by Ag feeding are important for the active
      transfer of oral tolerance in this murine experimental model of asthma.

PMID- 16424177
TI  - IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells.
AB  - IL-21 is a recently described cytokine, produced by activated Th cells, that
      shares significant homology with members of the IL-2 family of cytokines. IL-21
      mediates its biological effects via the IL-21R in conjunction with the common
      receptor gamma-chain that is also shared by members of the IL-2 family. We report
      that culture of human primary NK and CD8+ T cells with IL-21 in combination with
      IL-2 results in significant reduction of the cell surface expression of NKG2D,
      compared with that in cells treated with IL-2 alone. The reduced expression of
      NKG2D after IL-21 culture had functional consequences for NK cell function, as
      assessed by NKG2D-mediated redirected lysis assays and degranulation assays,
      compared with NK cells treated with IL-2 alone. IL-21-mediated NKG2D down
      regulation in human NK cells correlated with a marked reduction of DNAX
      activating protein of 10 kDa (DAP10) transcription in cells treated with IL-2 in
      combination with IL-21 compared with cells stimulated with only IL-2. This was
      attributed to a dramatic reduction in DAP10 promoter activity, as assessed by a
      DAP10 luciferase reporter construct. In contrast to NKG2D expression, IL-21 was
      able to induce the expression of the NK activation receptors NKp30 and 2B4 as
      well as the costimulatory receptor CD28 on CD8+ T cells. These data indicate that
      IL-21 is able to channel NK and CD8+ T cell function by altering the expression
      pattern of activation/costimulatory receptors.

PMID- 16424178
TI  - CD8 T cells, like CD4 T cells, are triggered by multivalent engagement of TCRs by
      MHC-peptide ligands but not by monovalent engagement.
AB  - T cell activation is initiated by recognition of antigenic peptide presented in
      complex with MHC molecules on the surface of APCs. The mechanism by which this
      recognition occurs is still unclear, and many models exist in the literature. CD4
      T cells have been shown to respond to soluble oligomers of activating class II
      MHC-peptide complexes, but not to soluble monomers. In determining the reactivity
      of CD8 T cells to soluble activating class I MHC-peptide complexes, a
      complicating phenomenon had been observed whereby peptide from soluble complexes
      was loaded onto cell surface MHCs on the T cells and re-presented to other T
      cells, clouding the true valency requirement for activation. This study uses
      soluble allogeneic class I MHC-peptide monomers and oligomers to stimulate murine
      CD8 T cells without the possible complication of peptide re-presentation. The
      results show that MHC class I monomers bind to, but do not activate, CD8 T cells
      whether the cells are in solution or adhered to a surface. Monomeric MHC class I
      binding can antagonize the stimulation triggered by soluble oligomers, a
      phenomenon also observed for CD4 T cells. Dimeric engagement is necessary and
      sufficient to stimulate downstream activation processes including TCR down
      regulation, Zap70 phosphorylation, and CD25 and CD69 up-regulation, even in T
      cells that do not express the MHC coreceptor CD8. Thus, the valency dependence of
      the response of CD8 T cells to soluble MHC-peptide reagents is the same as
      previously observed for CD4 T cells.

PMID- 16424179
TI  - Expansion of functionally immature transitional B cells is associated with human
      immunodeficient states characterized by impaired humoral immunity.
AB  - X-linked lymphoproliferative disease (XLP) is a severe immunodeficiency
      associated with a marked reduction in circulating memory B cells. Our
      investigation of the B cell compartment of XLP patients revealed an increase in
      the frequency of a population of B cells distinct from those previously defined.
      This population displayed increased expression of CD10, CD24, and CD38,
      indicating that it could consist of circulating immature/transitional B cells.
      Supporting this possibility, CD10+CD24highCD38high B cells displayed other
      immature characteristics, including unmutated Ig V genes and elevated levels of
      surface IgM; they also lacked expression of Bcl-2 and a panel of activation
      molecules. The capacity of CD24highCD38high B cells to proliferate, secrete Ig,
      and migrate in vitro was greatly reduced compared with mature B cell populations.
      Moreover, CD24highCD38high B cells were increased in the peripheral blood of
      neonates, patients with common variable immunodeficiency, and patients recovering
      from hemopoietic stem cell transplant. Thus, an expansion of functionally
      immature B cells may contribute to the humoral immunodeficient state that is
      characteristic of neonates, as well as patients with XLP or common variable
      immunodeficiency, and those recovering from a stem cell transplant. Further
      investigation of transitional B cells will improve our understanding of human B
      cell development and how alterations to this process may precipitate
      immunodeficiency or autoimmunity.

PMID- 16424180
TI  - CD27 dissects mature NK cells into two subsets with distinct responsiveness and
      migratory capacity.
AB  - Lineage differentiation and the formation of heterogeneous mature subsets are
      crucial for immune cells to maintain a breadth of responsiveness to pathogens
      while controlling reactivity to self. In this study, we report that CD27 is a key
      marker of the NK cell lineage, dissecting the mature Mac-1high NK cell pool into
      two functionally distinct subsets. The CD27low NK cell subset possesses a higher
      threshold to stimulation and appears to be tightly regulated by the expression of
      NK cell inhibitory receptors. Comparatively, the CD27high NK cell subset displays
      a greater effector function, exhibits a distinct tissue distribution and
      responsiveness to chemokines, and interacts productively with dendritic cells.
      Importantly, we have verified that CD27high and CD27low subsets with distinct
      cell surface phenotypes also exist in human peripheral blood. These findings
      clearly reclassify mature NK cells into two distinct subsets and begin to discern
      their specific role in immune responses.

PMID- 16424181
TI  - Therapeutic vaccination of active arthritis with a glycosylated collagen type II
      peptide in complex with MHC class II molecules.
AB  - In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells
      recognize a galactosylated peptide from type II collagen (CII). In this study, we
      demonstrate that the CII259-273 peptide, galactosylated at lysine 264, in complex
      with Aq molecules prevented development of CIA in mice and ameliorated chronic
      relapsing disease. In contrast, nonglycosylated CII259-273/Aq complexes had no
      such effect. CIA dependent on other MHC class II molecules (Ar/Er) was also down
      regulated, indicating a bystander vaccination effect. T cells could transfer the
      amelioration of CIA, showing that the protection is an active process. Thus, a
      complex between MHC class II molecules and a posttranslationally modified peptide
      offers a new possibility for treatment of chronically active autoimmune
      inflammation such as rheumatoid arthritis.

PMID- 16424182
TI  - Pregnancy-associated exosomes and their modulation of T cell signaling.
AB  - Exosome release by viable cells is a feature of activated cell types, including
      tumors, fetal cells, and cells of the immune system. Exosomes critically regulate
      immune activation, by mediating activation-induced cell death. Fetal cells may
      mimic these events to selectively delete reactive lymphocytes. In this study the
      presence and composition of placenta-derived exosomes are demonstrated in the
      maternal circulation along with their consequences on T cell activation markers.
      For all pregnant patients, exosomes were isolated from sera obtained between 28
      and 30 wk gestation. For pregnant women, subsequently delivering at term,
      circulating levels of placental exosomes were 1.8 times greater than those
      delivering preterm (p < 0.0001). Exosomes isolated from pregnancies subsequently
      delivering at term expressed significantly higher levels of biologically active
      components, including Fas ligand (FasL) and HLA-DR, than those from pregnancies
      delivering preterm. Standardizing for protein concentrations, exosomes from term
      delivering pregnancies exhibited greater suppression of CD3-zeta and JAK3 than
      those delivering preterm. The suppression of CD3-zeta and JAK3 correlated with
      exosome expression levels of FasL (r2= 0.92 and r2= 0.938, respectively).
      Fractionation of exosomes from term-delivering pregnancies by continuously
      eluting electrophoresis indicated that intact 42 kD FasL and an unidentified 24
      kDa protein were associated with CD3-zeta suppression. Our results demonstrated
      that exosomes from pregnancies ultimately delivering at term are present at
      significantly greater concentrations than those from pregnancies delivering
      preterm; however, exosomes from term-delivering pregnancies also exhibit
      significantly greater suppression of CD3-zeta and JAK3.

PMID- 16424183
TI  - Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements,
      intracellular TCR beta expression, and gamma delta developmental potential-
      differences between men and mice.
AB  - To evaluate the role of the TCR in the alphabeta/gammadelta lineage choice during
      human thymocyte development, molecular analyses of the TCRbeta locus in
      gammadelta cells and the TCRgamma and delta loci in alphabeta cells were
      undertaken. TCRbeta variable gene segments remained largely in germline
      configuration in gammadelta cells, indicating that commitment to the gammadelta
      lineage occurred before complete TCRbeta rearrangements in most cases. The few
      TCRbeta rearrangements detected were primarily out-of-frame, suggesting that
      productive TCRbeta rearrangements diverted cells away from the gammadelta
      lineage. In contrast, in alphabeta cells, the TCRgamma locus was almost
      completely rearranged with a random productivity profile; the TCRdelta locus
      contained primarily nonproductive rearrangements. Productive gamma rearrangements
      were, however, depleted compared with preselected cells. Productive TCRgamma and
      delta rearrangements rarely occurred in the same cell, suggesting that alphabeta
      cells developed from cells unable to produce a functional gammadelta TCR.
      Intracellular TCRbeta expression correlated with the up-regulation of CD4 and
      concomitant down-regulation of CD34, and plateaued at the early double positive
      stage. Surprisingly, however, some early double positive thymocytes retained
      gammadelta potential in culture. We present a model for human thymopoiesis which
      includes gammadelta development as a default pathway, an instructional role for
      the TCR in the alphabeta/gammadelta lineage choice, and a prolonged developmental
      window for beta selection and gammadelta lineage commitment. Aspects that differ
      from the mouse are the status of TCR gene rearrangements at the nonexpressed
      loci, the timing of beta selection, and maintenance of gammadelta potential
      through the early double positive stage of development.

PMID- 16424184
TI  - Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio
      of Th1 and Th2 cell differentiation.
AB  - The intrinsic features of naive CD4 T cells that affect their ability to respond
      to polarizing signals for Th cell differentiation are not well understood. In
      this study, we show that naive CD4 T cells from mice transgenic for the Hlx gene
      expressed lower levels of IL-4Ralpha. The down-regulation of IL-4Ralpha
      diminished IL-4 signaling and the Th2 response and enhanced the Th1 response
      under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL
      4Ralpha with Abs had the same effect in an Ab dose-dependent manner. Conversely,
      Hlx haploinsufficiency caused higher expression of IL-4Ralpha to favor Th2 cell
      differentiation. Thus, the IL-4Ralpha level on naive CD4 T cells is genetically
      controlled by Hlx and determines the ratio of Th1 and Th2 cell differentiation.

PMID- 16424186
TI  - Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection
      independent of their role in CD4+ T cell help.
AB  - Itk and Rlk are members of the Tec kinase family of nonreceptor protein tyrosine
      kinases that are expressed in T cells, NK cells, and mast cells. These proteins
      are involved in the regulation of signaling processes downstream of the TCR in
      CD4(+) T cells, particularly in the phosphorylation of phospholipase C-gamma1
      after TCR activation; furthermore, both Itk and Rlk are important in CD4(+) T
      cell development, differentiation, function, and homeostasis. However, few
      studies have addressed the roles of these kinases in CD8(+) T cell signaling and
      function. Using Itk(-/-) and Itk(-/-)Rlk(-/-) mice, we examined the roles of
      these Tec family kinases in CD8(+) T cells, both in vitro and in vivo. These
      studies demonstrate that the loss of Itk and Rlk impairs TCR-dependent signaling,
      causing defects in phospholipase C-gamma1, p38, and ERK activation as well as
      defects in calcium flux and cytokine production in vitro and expansion and
      effector cytokine production by CD8(+) T cells in response to viral infection.
      These defects cannot be rescued by providing virus-specific CD4(+) T cell help,
      thereby substantiating the important role of Tec kinases in CD8(+) T cell
      signaling.

PMID- 16424187
TI  - CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer.
AB  - CD4+CD25+ regulatory T cells (Treg) that suppress T cell-mediated immune
      responses may also regulate other arms of an effective immune response. In
      particular, in this study we show that Treg directly inhibit NKG2D-mediated NK
      cell cytotoxicity in vitro and in vivo, effectively suppressing NK cell-mediated
      tumor rejection. In vitro, Treg were shown to inhibit NKG2D-mediated cytolysis
      largely by a TGF-beta-dependent mechanism and independently of IL-10. Adoptively
      transferred Treg suppressed NK cell antimetastatic function in RAG-1-deficient
      mice. Depletion of Treg before NK cell activation via NKG2D and the activating IL
      12 cytokine, dramatically enhanced NK cell-mediated suppression of tumor growth
      and metastases. Our data illustrate at least one mechanism by which Treg can
      suppress NK cell antitumor activity and highlight the effectiveness of combining
      Treg inhibition with subsequent NK cell activation to promote strong innate
      antitumor immunity.

PMID- 16424185
TI  - TLR agonists abrogate costimulation blockade-induced prolongation of skin
      allografts.
AB  - Costimulation blockade protocols are effective in prolonging allograft survival
      in animal models and are entering clinical trials, but how environmental
      perturbants affect graft survival remains largely unstudied. We used a
      costimulation blockade protocol consisting of a donor-specific transfusion and
      anti-CD154 mAb to address this question. We observed that lymphocytic
      choriomeningitis virus infection at the time of donor-specific transfusion and
      anti-CD154 mAb shortens allograft survival. Lymphocytic choriomeningitis virus 1)
      activates innate immunity, 2) induces allo-cross-reactive T cells, and 3)
      generates virus-specific responses, all of which may adversely affect allograft
      survival. To investigate the role of innate immunity, mice given costimulation
      blockade and skin allografts were coinjected with TLR2 (Pam3Cys), TLR3
      (polyinosinic:polycytidylic acid), TLR4 (LPS), or TLR9 (CpG) agonists.
      Costimulation blockade prolonged skin allograft survival that was shortened after
      coinjection by TLR agonists. To investigate underlying mechanisms, we used
      "synchimeric" mice which circulate trace populations of anti-H2b transgenic
      alloreactive CD8+ T cells. In synchimeric mice treated with costimulation
      blockade, coadministration of all four TLR agonists prevented deletion of
      alloreactive CD8+ T cells and shortened skin allograft survival. These
      alloreactive CD8+ T cells 1) expressed the proliferation marker Ki-67, 2) up
      regulated CD44, and 3) failed to undergo apoptosis. B6.TNFR2-/- and B6.IL-12R-/-
      mice treated with costimulation blockade plus LPS also exhibited short skin
      allograft survival whereas similarly treated B6.CD8alpha-/- and TLR4-/- mice
      exhibited prolonged allograft survival. We conclude that TLR signaling abrogates
      the effects of costimulation blockade by preventing alloreactive CD8+ T cell
      apoptosis through a mechanism not dependent on TNFR2 or IL-12R signaling.

PMID- 16424188
TI  - Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent
      tolerance to experimental autoimmune encephalomyelitis.
AB  - Heat shock proteins (Hsp) are markedly up-regulated at sites of inflammation
      during autoimmune diseases like experimental autoimmune encephalomyelitis (EAE).
      In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of
      mice with EAE prevented the development of EAE clinically and pathologically when
      administered before proteolipid protein 139-151 (PLP139-151) immunization. In
      contrast, pure Hsp70 or Hsp70-pc derived from brains of healthy mice or other
      inflamed tissue did not modulate the expression of EAE. In animals in which EAE
      had been suppressed by Hsp70-pc, lymphocytes showed increased cell death in
      response to PLP139-151 that correlated with elevated IFN-gamma and NO production.
      Coculture of spleen cells from Hsp70-pc immunized mice with spleen cells from
      untreated EAE mice, in addition to depletion experiments, showed that NK cells
      reduced reactivity to PLP139-151. Transfer of NK cells from Hsp70-pc-immunized
      mice to recipients sensitized for EAE abolished disease development. Thus, we
      propose that Hsp70 demonstrate the ability to bind to peptides generated during
      brain inflammation and to induce a regulatory NK cell population that is capable
      of preventing subsequent autoimmunization for EAE.

PMID- 16424189
TI  - Respiratory syncytial virus G protein and G protein CX3C motif adversely affect
      CX3CR1+ T cell responses.
AB  - Interactions between fractalkine (CX3CL1) and its receptor, CX3CR1, mediate
      leukocyte adhesion, activation, and trafficking. The respiratory syncytial virus
      (RSV) G protein has a CX3C chemokine motif that can bind CX3CR1 and modify CXCL1
      mediated responses. In this study, we show that expression of the RSV G protein
      or the G protein CX3C motif during infection is associated with reduced CX3CR1+ T
      cell trafficking to the lung, reduced frequencies of RSV-specific, MHC class I
      restricted IFN-gamma-expressing cells, and lower numbers of IL-4- and CX3CL1
      expressing cells. In addition, we show that CX3CR1+ cells constitute a major
      component of the cytotoxic response to RSV infection. These results suggest that
      G protein and the G protein CX3C motif reduce the antiviral T cell response to
      RSV infection.

PMID- 16424190
TI  - CD4+CD25+ regulatory T cells inhibit the antigen-dependent expansion of self
      reactive T cells in vivo.
AB  - A deficiency of CD4+CD25+ regulatory T cells (CD25+ Tregs) in lymphopenic mice
      can result in the onset of autoimmune gastritis. The gastric H/K ATPase alpha
      (H/Kalpha) and beta (H/Kbeta) subunits are the immunodominant autoantigens
      recognized by effector CD4+ T cells in autoimmune gastritis. The mechanism by
      which CD25+ Tregs suppress autoimmune gastritis in lymphopenic mice is poorly
      understood. To investigate the antigenic requirements for the genesis and
      survival of gastritis-protecting CD25+ Tregs, we analyzed mice deficient in
      H/Kbeta and H/Kalpha, as well as a transgenic mouse line (H/Kbeta-tsA58 Tg line
      224) that lacks differentiated gastric epithelial cells. By adoptive transfer of
      purified T cell populations to athymic mice, we show that the CD25+ Treg
      population from mice deficient in either one or both of H/Kalpha and H/Kbeta, or
      from the H/Kbeta-tsA58 Tg line 224 mice, is equally effective in suppressing the
      ability of polyclonal populations of effector CD4+ T cells to induce autoimmune
      gastritis. Furthermore, CD25+ Tregs, from either wild-type or H/Kalpha-deficient
      mice, dramatically reduced the expansion of pathogenic H/Kalpha-specific TCR
      transgenic T cells and the induction of autoimmune gastritis in athymic recipient
      mice. Proliferation of H/Kalpha-specific T cells in lymphopenic hosts occurs
      predominantly in the paragastric lymph node and was dependent on the presence of
      the cognate H/Kalpha Ag. Collectively, these studies demonstrate that the
      gastritis-protecting CD25+ Tregs do not depend on the major gastric Ags for their
      thymic development or their survival in the periphery, and that CD25+ Tregs
      inhibit the Ag-specific expansion of pathogenic T cells in vivo.

PMID- 16424191
TI  - MR1-restricted V alpha 19i mucosal-associated invariant T cells are innate T
      cells in the gut lamina propria that provide a rapid and diverse cytokine
      response.
AB  - Mucosal-associated invariant T (MAIT) cells reside primarily in the gut lamina
      propria and require commensal flora for selection/expansion. They are restricted
      by the highly conserved MHC class I-related molecule MR1 and, like most NK T
      cells, express an invariant TCRalpha chain. Although they probably contribute to
      gut immunity, MAIT cells have not been functionally characterized because they
      are so rare. To create a model in which they are more abundant, we generated
      transgenic mice expressing only the TCRalpha chain (Valpha19i) that defines MAIT
      cells. By directly comparing Valpha19i transgenic mice on MR1+/+ and MR1-/-
      backgrounds, we were able to distinguish and characterize a population of
      Valpha19i T cells dependent on MR1 for development. MR1-restricted Valpha19i
      transgenic T cells recapitulate what is known about MAIT cell development.
      Furthermore, a relatively high proportion of transgenic MAIT cells express NK1.1,
      and most have a cell surface phenotype similar to that of Valpha14i NK T cells.
      Finally, MR1-restricted Valpha19i T cells secrete IFN-gamma, IL-4, IL-5, and IL
      10 following TCR ligation, and we provide evidence for what may be two
      functionally distinct MAIT cell populations. These data strongly support the idea
      that MAIT cells contribute to the innate immune response in the gut mucosa.

PMID- 16424192
TI  - Cross-positive selection of thymocytes expressing a single TCR by multiple major
      histocompatibility complex molecules of both classes: implications for CD4+
      versus CD8+ lineage commitment.
AB  - This study has investigated the cross-reactivity upon thymic selection of
      thymocytes expressing transgenic TCR derived from a murine CD8+ CTL clone. The
      Idhigh+ cells in this transgenic mouse had been previously shown to mature
      through positive selection by class I MHC, Dq or Lq molecule. By investigating on
      various strains, we found that the transgenic TCR cross-reacts with three
      different MHCs, resulting in positive or negative selection. Interestingly, in
      the TCR-transgenic mice of H-2q background, mature Idhigh+ T cells appeared among
      both CD4+ and CD8+ subsets in periphery, even in the absence of RAG-2 gene. When
      examined on beta2-microglobulin-/- background, CD4+, but not CD8+, Idhigh+ T
      cells developed, suggesting that maturation of CD8+ and CD4+ Idhigh+ cells was
      MHC class I (Dq/Lq) and class II (I-Aq) dependent, respectively. These results
      indicated that this TCR-transgenic mouse of H-2q background contains both classes
      of selecting MHC ligands for the transgenic TCR simultaneously. Further genetic
      analyses altering the gene dosage and combinations of selecting MHCs suggested
      novel asymmetric effects of class I and class II MHC on the positive selection of
      thymocytes. Implications of these observations in CD4+/CD8+ lineage commitment
      are discussed.

PMID- 16424193
TI  - Early autoimmune destruction of islet grafts is associated with a restricted
      repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice.
AB  - beta cell replacement via islet or pancreas transplantation is currently the only
      approach to cure type 1 diabetic patients. Recurrent beta cell autoimmunity is a
      critical factor contributing to graft rejection along with alloreactivity.
      However, the specificity and dynamics of recurrent beta cell autoimmunity remain
      largely undefined. Accordingly, we compared the repertoire of CD8+ T cells
      infiltrating grafted and endogenous islets in diabetic nonobese diabetic mice. In
      endogenous islets, CD8+ T cells specific for an islet-specific glucose-6
      phosphatase catalytic subunit-related protein derived peptide (IGRP206-214) were
      the most prevalent T cells. Similar CD8+ T cells dominated the early graft
      infiltrate but were expanded 6-fold relative to endogenous islets. Single-cell
      analysis of the TCR alpha and beta chains showed restricted variable gene usage
      by IGRP206-214-specific CD8+ T cells that was shared between the graft and
      endogenous islets of individual mice. However, as islet graft infiltration
      progressed, the number of IGRP206-214-specific CD8+ T cells decreased despite
      stable numbers of CD8+ T cells. These results demonstrate that recurrent beta
      cell autoimmunity is characterized by recruitment to the grafts and expansion of
      already prevalent autoimmune T cell clonotypes residing in the endogenous islets.
      Furthermore, depletion of IGRP206-214-specific CD8+ T cells by peptide
      administration delayed islet graft survival, suggesting IGRP206-214-specific CD8+
      T cells play a role early in islet graft rejection but are displaced with time by
      other specificities, perhaps by epitope spread.

PMID- 16424194
TI  - NKT cells and IFN-gamma establish the regulatory environment for the control of
      diabetogenic T cells in the nonobese diabetic mouse.
AB  - In type 1 diabetes mellitus (T1DM), T cell-mediated destruction of insulin
      producing pancreatic beta cells leads to the acute onset of hyperglycemia. The
      nonobese diabetic mouse model of human T1DM reveals that T cells capable of
      inducing diabetes can escape normal central tolerance, and can cause T1DM if left
      unchecked. However, several regulatory T cell subsets can temper autoaggressive T
      cells, although it remains undetermined when and how, and by which subset,
      homeostatic control of diabetogenic T cells is normally achieved in vivo. Using a
      cotransfer model, we find that NKT cells efficiently dampen the action of
      diabetogenic CD4+ T cells, and do so in an indirect manner by modifying the host
      environment. Moreover, the NKT cell-containing population modifies the host via
      production of IFN-gamma that is necessary for driving the inhibition of
      diabetogenic T cells in vivo.

PMID- 16424195
TI  - The nucleotide targets of somatic mutation and the role of selection in
      immunoglobulin heavy chains of a teleost fish.
AB  - Sequence analysis of H chain cDNA derived from the spleen of an individual
      catfish has shown that somatic mutation occurs within both the VH- and JH-encoded
      regions. Somatic mutation preferentially targets G and C nucleotides with
      approximately balanced frequencies, resulting in the predominant accumulation of
      G-to-A and C-to-T substitutions that parallel the activation-induced cytidine
      deaminase nucleotide exchanges known in mammals. The overall mutation rate of A
      nucleotides is not significantly different from that expected by sequence
      insensitive mutations, and a significant bias exists against mutations occurring
      in T. Targeting of mutations is dependent upon the sequence of neighboring
      nucleotides, allowing statistically significant hotspot motifs to be identified.
      Dinucleotide, trinucleotide, and RGYW analyses showed that mutational targets in
      catfish are restricted when compared with the spectrum of targets known in
      mammals. The preferential targets for G and C mutation are the central GC
      positions in both AGCT and AGCA. The WA motif, recognized as a mammalian hotspot
      for A mutations, was not a significant target for catfish mutations. The only
      significant target for A mutations was the terminal position in AGCA. Lastly,
      comparisons of mutations located in framework region and CDR codons coupled with
      multinomial distribution studies found no substantial evidence in either
      independent or clonally related VDJ rearrangements to indicate that somatic
      mutation coevolved with mechanisms that select B cells based upon nonsynonymous
      mutations within CDR-encoded regions. These results suggest that the principal
      role of somatic mutation early in phylogeny was to diversify the repertoire by
      targeting hotspot motifs preferentially located within CDR-encoded regions.

PMID- 16424196
TI  - Phosphatidylinositol 3-kinase functions as a Ras effector in the signaling
      cascade that regulates dephosphorylation of the actin-remodeling protein cofilin
      after costimulation of untransformed human T lymphocytes.
AB  - The activity of cofilin, an actin-remodeling protein, is required for T
      lymphocyte activation with regard to formation of the immunological synapse,
      cytokine production, and proliferation. In unstimulated T PBL (PB-T), cofilin is
      present in its Ser3-phosphorylated inactive form. Costimulation of TCR/CD3 and
      CD28 induces dephosphorylation and, thus, activation of cofilin. In this study we
      characterized the signaling cascades leading to cofilin activation in
      untransformed human PB-T. We show that a Ras-PI3K cascade regulates
      dephosphorylation of cofilin in PB-T. The GTPase Ras is a central mediator of
      this pathway; transient expression of an activated form of H-Ras in PB-T
      triggered the dephosphorylation of cofilin. Inhibition of either MAPK/ERK kinase
      or PI3K blocked both Ras-induced and costimulation-induced cofilin
      dephosphorylation in PB-T, showing that the combined activities of both signaling
      proteins are required to activate cofilin. That Ras functions as a central
      regulator of cofilin dephosphorylation after costimulation through CD3 x CD28 was
      finally proven by transient expression of a dominant negative form of H-Ras in
      primary human PB-T. It clearly inhibited costimulation-induced cofilin
      dephosphorylation, and likewise, activation of PI3K was diminished. Our data, in
      addition, demonstrate that regarding the downstream effectors of Ras, a clear
      difference exists between untransformed human PB-T and the T lymphoma line
      Jurkat. Thus, in PB-T the Ras signaling cascade is able to activate PI3K, whereas
      in Jurkat cells this is not the case. In addition to the insights into the
      regulation of cofilin, this finding discloses a to date unrecognized possibility
      of PI3K activation in T lymphocytes.

PMID- 16424197
TI  - Opioids trigger alpha 5 beta 1 integrin-mediated monocyte adhesion.
AB  - Inflammatory reactions involve a network of chemical and molecular signals that
      initiate and maintain host response. In inflamed tissue, immune system cells
      generate opioid peptides that contribute to potent analgesia by acting on
      specific peripheral sensory neurons. In this study, we show that opioids also
      modulate immune cell function in vitro and in vivo. By binding to its specific
      receptor, the opioid receptor-specific ligand DPDPE triggers monocyte adhesion.
      Integrins have a key role in this process, as adhesion is abrogated in cells
      treated with specific neutralizing anti-alpha5beta1 integrin mAb. We found that
      DPDPE-triggered monocyte adhesion requires PI3Kgamma activation and involves Src
      kinases, the guanine nucleotide exchange factor Vav-1, and the small GTPase Rac1.
      DPDPE also induces adhesion of pertussis toxin-treated cells, indicating
      involvement of G proteins other than Gi. These data show that opioids have
      important implications in regulating leukocyte trafficking, adding a new function
      to their known effects as immune response modulators.

PMID- 16424198
TI  - Characterization of functional oligosaccharide mimics of the Shigella flexneri
      serotype 2a O-antigen: implications for the development of a chemically defined
      glycoconjugate vaccine.
AB  - Protection against reinfection with noncapsulated Gram-negative bacteria, such as
      Shigella, an enteroinvasive bacterium responsible for bacillary dysentery, is
      mainly achieved by Abs specific for the O-Ag, the polysaccharide part of the LPS,
      the major bacterial surface Ag. The use of chemically defined glycoconjugates
      encompassing oligosaccharides mimicking the protective determinants carried by
      the O-Ag, thus expected to induce an efficient anti-LPS Ab response, has been
      considered an alternative to detoxified LPS-protein conjugate vaccines. The aim
      of this study was to identify such functional oligosaccharide mimics of the S.
      flexneri serotype 2a O-Ag. Using protective murine mAbs specific for S. flexneri
      serotype 2a and synthetic oligosaccharides designed to analyze the contribution
      of each sugar residue of the branched pentasaccharide repeating unit of the O-Ag,
      we demonstrated that the O-Ag exhibited an immunodominant serotype-specific
      determinant. We also showed that elongating the oligosaccharide sequence improved
      Ab recognition. From these antigenicity data, selected synthetic oligosaccharides
      were assessed for their potential to mimic the O-Ag by analyzing their
      immunogenicity in mice when coupled to tetanus toxoid via single point
      attachment. Our results demonstrated that induction of an efficient serotype 2a
      specific anti-O-Ag Ab response was dependent on the length of the oligosaccharide
      sequence. A pentadecasaccharide representing three biological repeating units was
      identified as a potential candidate for further development of a chemically
      defined glycoconjugate vaccine against S. flexneri 2a infection.

PMID- 16424199
TI  - Glucocorticoids engage different signal transduction pathways to induce apoptosis
      in thymocytes and mature T cells.
AB  - Glucocorticoids (GC) induce apoptosis in a variety of cells, but their exact mode
      of action is controversial. Although initiation relies on the GC receptor (GR)
      and de novo gene expression, the effector phase differs among cell types.
      Proteasomal degradation as well as caspase-3, - 8, and -9 activity are essential
      for GC-induced apoptosis in murine thymocytes, but the same enzymes are
      dispensable in splenic T cells. Live imaging by confocal microscopy revealed that
      lysosomal cathepsin B, an unrecognized component of this pathway to date, becomes
      rapidly activated in thymocytes after GC exposure. This is followed by leakage of
      cathepsin B into the cytosol, nuclear condensation, and processing of caspase-8
      and -3. According to our model, activation of caspase-3 by caspase-9 in
      thymocytes occurs both directly as well as indirectly via a lysosomal
      amplification loop. Interestingly, acute T lymphoblastic leukemia cells depend on
      caspase activity to undergo GC-induced cell death similar to thymocytes.
      Collectively, the apoptotic program induced by GCs comprises cell type-specific
      as well as common features.

PMID- 16424200
TI  - Qa-1b and CD94-NKG2a interaction regulate cytolytic activity of herpes simplex
      virus-specific memory CD8+ T cells in the latently infected trigeminal ganglia.
AB  - After ocular infection, HSV-specific CD8+ T cells migrate to and are specifically
      retained in the ophthalmic branch of the trigeminal ganglia (TG) even at the time
      when replicating virus is no longer evident. Virus-specific CD8+ T cells maintain
      an activation phenotype and secrete IFN-gamma in the latent TG. In this report we
      demonstrated that activated virus-specific memory CD8+ T cells, although
      potentially cytolytic, also expressed the CD94-NK cell receptor subfamily G2a
      inhibitory molecule and were unable to exert cytotoxicity when engaged by Qa-1b
      expressing targets. Interestingly, many neurons in the latent TG expressed Qa-1b,
      and blocking of Qa-1b/CD94-NKG2a interaction in an ex vivo TG culture resulted in
      neuronal cell lysis. The expression of the inhibitory CD94-NKG2a molecule could
      be induced by TGF-beta1, which was shown to present as a bioactive molecule in
      the latent TG. Additionally, CD4+ forkhead/winged helix transcription factor 3+ T
      cells were also determined in the latent TG. Our results demonstrate the
      operation of a regulatory system in vivo that serves to protect irreplaceable
      neurons from destruction by the immune system.

PMID- 16424201
TI  - Immunity and tolerance to Aspergillus involve functionally distinct regulatory T
      cells and tryptophan catabolism.
AB  - The inherent resistance to diseases caused by Aspergillus fumigatus suggests the
      occurrence of regulatory mechanisms that provide the host with adequate defense
      without necessarily eliminating the fungus or causing unacceptable levels of host
      damage. In this study, we show that a division of labor occurs between
      functionally distinct regulatory T cells (Treg) that are coordinately activated
      by a CD28/B-7-dependent costimulatory pathway after exposure of mice to
      Aspergillus conidia. Early in infection, inflammation is controlled by the
      expansion, activation and local recruitment of CD4+CD25+ Treg capable of
      suppressing neutrophils through the combined actions of IL-10 and CTLA-4 on
      indoleamine 2,3-dioxygenase. The levels of IFN-gamma produced in this early phase
      set the subsequent adaptive stage by conditioning the indoleamine 2,3-dioxygenase
      dependent tolerogenic program of dendritic cells and the subsequent activation
      and expansion of tolerogenic Treg, which produce IL-10 and TGF-beta, inhibit Th2
      cells, and prevent allergy to the fungus. The coordinate activation of Treg may,
      however, be subverted by the fungus, as germinating conidia are capable of
      interfering with anti-inflammatory and tolerogenic Treg programs. Thus,
      regulation is an essential component of the host response in infection and
      allergy to the fungus, and its manipulation may allow the pathogen to overcome
      host resistance and promote disease.

PMID- 16424202
TI  - Experimental African trypanosomiasis: a subset of pathogenic, IFN-gamma
      producing, MHC class II-restricted CD4+ T cells mediates early mortality in
      highly susceptible mice.
AB  - Infections of highly susceptible BALB/c mice with virulent strains of Trypanosoma
      congolense or Trypanosoma brucei result in rapid death (8 days). We have
      previously shown that this mortality is IFN-gamma dependent. In this study we
      show that IFN-gamma is produced predominantly by CD3+Thy1.2+TCRbeta+CD4+ T cells
      shortly before the death of infected mice. Mortality may therefore be dependent
      on IFN-gamma-producing CD4+ T cells. Surprisingly, infected CD4+/+ and CD4-/-
      BALB/c mice have similar parasitemia and survival time. In infected CD4-/- mice,
      the production of both IFN-gamma and IL-10 is very low, suggesting that both
      cytokines are predominantly produced by CD4+ T cells and that the outcome of the
      disease might depend on the balance of their effects. Infected BALB/c mice
      partially depleted of CD4+ T cells or MHC class II function have lower
      parasitemia and survive significantly longer than infected normal BALB/c mice or
      infected BALB/c mice whose CD4+ T cells are fully depleted. Partial depletion of
      CD4+ T cells markedly reduces IFN-gamma secretion without a major effect on the
      production of IL-10 and parasite-specific IgG2a Abs. Based on our previous and
      current data, we conclude that a subset of a pathogenic, MHC class II-restricted
      CD4+ T cells (Tp cells), activated during the course of T. congolense infection,
      mediates early mortality in infected BALB/c mice via excessive synthesis of IFN
      gamma. IFN-gamma, in turn, exerts its pathological effect by enhancing the
      cytokine release syndrome of the macrophage system activated by the phagocytosis
      of parasites. We speculate that IL-10-producing CD4+ T cells might counteract
      this effect.

PMID- 16424203
TI  - Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to
      increased double-stranded RNA responsiveness in airway epithelial cells.
AB  - Respiratory syncytial virus (RSV) preferentially infects airway epithelial cells,
      causing bronchiolitis, upper respiratory infections, asthma exacerbations,
      chronic obstructive pulmonary disease exacerbations, and pneumonia in
      immunocompromised hosts. A replication intermediate of RSV is dsRNA. This is an
      important ligand for both the innate immune receptor, TLR3, and protein kinase R
      (PKR). One known effect of RSV infection is the increased responsiveness of
      airway epithelial cells to subsequent bacterial ligands (i.e., LPS). In this
      study, we examined a possible role for RSV infection in increasing amounts and
      responsiveness of another TLR, TLR3. These studies demonstrate that RSV infection
      of A549 and human tracheobronchial epithelial cells increases the amounts of TLR3
      and PKR in a time-dependent manner. This leads to increased NF-kappaB activity
      and production of the inflammatory cytokine IL-8 following a later exposure to
      dsRNA. Importantly, TLR3 was not detected on the cell surface at baseline but was
      detected on the cell surface after RSV infection. The data demonstrate that RSV,
      via an effect on TLR3 and PKR, sensitizes airway epithelial cells to subsequent
      dsRNA exposure. These findings are consistent with the hypothesis that RSV
      infection sensitizes the airway epithelium to subsequent viral and bacterial
      exposures by up-regulating TLRs and increasing their membrane localization.

PMID- 16424204
TI  - DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages.
AB  - Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma and pleural effusion
      lymphoma. In this study, we show that dendritic cell-specific ICAM-3 grabbing
      nonintegrin (DC-SIGN; CD209) is a receptor for HHV-8 infection of myeloid DCs and
      macrophages. DC-SIGN was required for virus attachment to these cells and DC-SIGN
      expressing cell lines. HHV-8 binding and infection were blocked by anti-DC-SIGN
      mAb and soluble DC-SIGN, and mannan, a natural ligand for DC-SIGN. Infection of
      DCs and macrophages with HHV-8 led to production of viral proteins, with little
      production of viral DNA, similar to HHV-8 infection of vascular endothelial
      cells. Infection of DCs resulted in down-regulation of DC-SIGN, a decrease in
      endocytic activity, and an inhibition of Ag stimulation of CD8+ T cells. We
      propose that DC-SIGN serves as a portal for immune dysfunction and oncogenesis
      caused by HHV-8 infection.

PMID- 16424205
TI  - CD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an
      IL-21-secreting cellular vaccine.
AB  - IL-21 is an IL-2-like cytokine, signaling through a specific IL-21R and the IL-2R
      gamma-chain. Because the TS/A mammary adenocarcinoma cells genetically modified
      to secrete IL-21 (TS/A-IL-21) are strongly immunogenic in syngeneic mice, we
      analyzed their application as vaccine. In mice bearing TS/A-parental cell (pc)
      micrometastases, vaccination with irradiated TS/A-IL-21 cells significantly
      increased the animal life span, but cured only 17% of mice. Spleen cells from
      cured mice developed CTL activity and produced IFN-gamma in response to
      stimulation by the AH1 epitope of the gp70env Ag of TS/A-pc. We tested whether
      the low therapeutic outcome might be due to CD4+CD25+ regulatory T cells (Treg)
      present in TS/A-pc tumors and draining lymph nodes and whether IL-21 had any
      effect on these cells. Indeed, CD4+CD25+ cells suppressed IFN-gamma production by
      splenocytes from immune mice in response to stimulation by the AH1 peptide. Low
      concentrations of IL-21 (10 ng/ml) failed to reverse the inhibitory activity of
      CD4+CD25+ cells in an allogeneic MLR, whereas 60 ng/ml rIL-21 partially restored
      responder T cell proliferation. IL-21R expression on CD25- lymphocytes suggested
      that IL-21 could be more effective in mice depleted of CD25+ cells. Depletion of
      Treg cells by a single dose of anti-CD25 mAb combined with TS/A-IL-21 cell
      vaccine cured >70% of mice bearing micrometastases, whereas anti-CD25 mAb
      treatment alone had no effect. Successful combined immunotherapy required NK
      cells, CD8+ T cells, and IFN-gamma. In conclusion, immunotherapy of
      micrometastases by an IL-21-based cellular vaccine is strongly potentiated by
      CD25+ cell depletion.

PMID- 16424206
TI  - Immunological characterization and antibacterial function of persisting
      granulocytes in leukemic patients receiving pulse cytosine arabinoside
      consolidation chemotherapy on days 1, 3, and 5.
AB  - High-dose cytosine arabinoside (HiDAC) and intermediate-dose cytosine arabinoside
      (IDAC) have been introduced as effective and safe consolidation chemotherapy in
      acute myeloid leukemia, with relatively low rates of life-threatening infections
      despite the high total dose of the cytostatic drug. To explore the biological
      background of low toxicity, we examined the numbers, immunophenotype, and
      functional properties of granulocytes in patients with acute myeloid leukemia
      receiving HiDAC or IDAC. Interestingly, the absolute numbers of neutrophils
      remained >500/microl until day 10 in 92 of 125 (74%) HiDAC cycles and in 106 of
      113 (94%) IDAC cycles. As assessed by electron microscopy, these day-10
      granulocytes surviving chemotherapy were found to be mature cells containing
      secondary granules and phagolysosomes. They also expressed opsonization- and
      phagocytosis-linked surface Ags (C3biR, CR1, C1qR, C5aR, FcgammaRI, FcgammaRII,
      FcgammaRIII, and G-CSF and GM-CSF receptors) like neutrophils in healthy
      controls. Moreover, these day-10 neutrophils exhibited oxidative burst activity
      and took up and digested bacteria in the same way as neutrophils in healthy
      controls. There was a negative correlation between absolute neutrophil counts and
      severe infections in HiDAC- and IDAC-treated patients with a later onset of
      infections in IDAC patients (median: IDAC, day 18; HiDAC, day 16). Together,
      functionally mature neutrophils are detectable at least until day 10 in patients
      treated with HiDAC or IDAC, and may explain the relatively low hematologic
      toxicity of these consolidation protocols. IDAC is a superior protocol in this
      regard and may therefore be most suitable for elderly patients and those at high
      risk for severe infections.

PMID- 16424208
TI  - Bacillus anthracis edema toxin acts as an adjuvant for mucosal immune responses
      to nasally administered vaccine antigens.
AB  - Anthrax edema toxin (EdTx) is an AB-type toxin that binds to anthrax toxin
      receptors on target cells via the binding subunit, protective Ag (PA). Edema
      factor, the enzymatic A subunit of EdTx, is an adenylate cyclase. We found that
      nasal delivery of EdTx enhanced systemic immunity to nasally coadministered OVA
      and resulted in high OVA-specific plasma IgA and IgG (mainly IgG1 and IgG2b). The
      edema factor also enhanced immunity to the binding PA subunit itself and promoted
      high levels of plasma IgG and IgA responses as well as neutralizing PA Abs. Mice
      given OVA and EdTx also exhibited both PA- and OVA-specific IgA and IgG Ab
      responses in saliva as well as IgA Ab responses in vaginal washes. EdTx as
      adjuvant triggered OVA- and PA-specific + T cells which secreted IFN-gamma and
      selected Th2-type cytokines. The EdTx up-regulated costimulatory molecule
      expression by APCs but was less effective than cholera toxin for inducing IL-6
      responses either by APCs in vitro or in nasal washes in vivo. Finally, nasally
      administered EdTx did not target CNS tissues and did not induce IL-1 mRNA
      responses in the nasopharyngeal-associated lymphoepithelial tissue or in the
      olfactory bulb epithelium. Thus, EdTx derivatives could represent an alternative
      to the ganglioside-binding enterotoxin adjuvants and provide new tools for
      inducing protective immunity to PA-based anthrax vaccines.

PMID- 16424209
TI  - Induction of positive cellular and humoral immune responses by a prime-boost
      vaccine encoded with simian immunodeficiency virus gag/pol.
AB  - It is believed likely that immune responses are responsible for controlling viral
      load and infection. In this study, when macaques were primed with plasmid DNA
      encoding SIV gag and pol genes (SIVgag/pol DNA) and then boosted with replication
      deficient vaccinia virus DIs recombinant expressing the same genes
      (rDIsSIVgag/pol), this prime-boost regimen generated higher levels of Gag
      specific CD4+ and CD8+ T cell responses than did either SIVgag/pol DNA or
      rDIsSIVgag/pol alone. When the macaques were i.v. challenged with pathogenic
      simian/HIV, the prime-boost group maintained high CD4+ T cell counts and reduced
      plasma viral loads up to 30 wk after viral challenge, whereas the rDIsSIVgag/pol
      group showed only a partial attenuation of the viral infection, and the group
      immunized with SIVgag/pol DNA alone showed none at all. The protection levels
      were better correlated with the levels of virus-specific T cell responses than
      the levels of neutralization Ab responses. These results demonstrate that a
      vaccine regimen that primes with DNA and then boosts with a replication-defective
      vaccinia virus DIs generates anti-SIV immunity, suggesting that it will be a
      promising vaccine regimen for HIV-1 vaccine development.

PMID- 16424210
TI  - Identification of cross-reactive peptides using combinatorial libraries
      circumvents tolerance against Her-2/neu-immunodominant epitope.
AB  - The majority of the currently defined tumor-associated Ags are often
      overexpressed products of normal cellular genes. Therefore, tolerance deletes
      high-affinity T cells directed against the TAAs, leaving only a low-affinity
      repertoire. We have demonstrated previously that the T cell repertoire against
      the immunodominant p773-782 A2.1-Her-2/neu-restricted peptide has low affinity in
      A2xneu mice (Her-2/neu mice crossed with A2.1/Kb mice), compared with A2xFVB mice
      (A2.1/Kb crossed with FVB-wild-type mice). Immunizations with this peptide have a
      minor impact in preventing tumor growth in A2xneu mice. Therefore, attempts to
      expand these responses may be of little clinical value. We hypothesized that if
      not all possible cross-reactive peptides (CPs) are naturally processed and
      presented, the possibility exists that T cells against these CPs persist in the
      repertoire and can be used to induce antitumor responses with higher avidity
      against native epitopes present on the tumor cells. We have used the positional
      scanning synthetic peptide combinatorial library methodology to screen the p773
      782 T cell clone. The screening data identified potential amino acids that can be
      substituted in the primary sequences of the p773-782 peptide. The designed CPs
      induce CTL responses of higher affinity in A2xneu mice compared with the native
      p773-783 peptide. These CTLs recognize A2+-Her-2/neu(+) tumors with high
      efficiency. Moreover, multiple immunizations with CPs significantly prolonged the
      survival of tumor-bearing A2xneu mice. These results have demonstrated that it
      was possible to circumvent tolerance with the identification of CPs and that
      these peptides could be of significant clinical value.

PMID- 16424207
TI  - Deficiency of mannose-binding lectin greatly increases susceptibility to postburn
      infection with Pseudomonas aeruginosa.
AB  - Burn injury disrupts the mechanical and biological barrier that the skin presents
      against infection by symbionts like the Pseudomonas aeruginosa, a Gram-negative
      bacteria. A combination of local factors, antimicrobial peptides, and resident
      effector cells form the initial response to mechanical injury of the skin. This
      activity is followed by an inflammatory response that includes influx of
      phagocytes and serum factors, such as complement and mannose-binding lectin
      (MBL), which is a broad-spectrum pattern recognition molecule that plays a key
      role in innate immunity. A growing consensus from studies in humans and mice
      suggests that lack of MBL together with other comorbid factors predisposes the
      host to infection. In this study we examined whether MBL deficiency increases the
      risk of P. aeruginosa infection in a burned host. We found that both wild-type
      and MBL null mice were resistant to a 5% total body surface area burn alone or
      s.c. infection with P. aeruginosa alone. However, when mice were burned then
      inoculated s.c. with P. aeruginosa at the burn site, all MBL null mice died by 42
      h from septicemia, whereas only one-third of wild-type mice succumbed (p =
      0.0005). This result indicates that MBL plays a key role in containing and
      preventing a systemic spread of P. aeruginosa infection following burn injury and
      suggests that MBL deficiency in humans maybe a premorbid variable in the
      predisposition to infection in burn victims.

PMID- 16424211
TI  - Human macrophages do not require phagosome acidification to mediate
      fungistatic/fungicidal activity against Histoplasma capsulatum.
AB  - Histoplasma capsulatum (Hc) is a facultative intracellular fungus that modulates
      the intraphagosomal environment to survive within macrophages (Mphi). In the
      present study, we sought to quantify the intraphagosomal pH under conditions in
      which Hc yeasts replicated or were killed. Human Mphi that had ingested both
      viable and heat-killed or fixed yeasts maintained an intraphagosomal pH of
      approximately 6.4-6.5 over a period of several hours. These results were obtained
      using a fluorescent ratio technique and by electron microscopy using the 3-(2,4
      dinitroanilo)-3'-amino-N-methyldipropylamine reagent. Mphi that had ingested
      Saccharomyces cerevisae, a nonpathogenic yeast that is rapidly killed and
      degraded by Mphi, also maintained an intraphagosomal pH of approximately 6.5 over
      a period of several hours. Stimulation of human Mphi fungicidal activity by
      coculture with chloroquine or by adherence to type 1 collagen matrices was not
      reversed by bafilomycin, an inhibitor of the vacuolar ATPase. Human Mphi cultured
      in the presence of bafilomycin also completely degraded heat-killed Hc yeasts,
      whereas mouse peritoneal Mphi digestion of yeasts was completely reversed in the
      presence of bafilomycin. However, bafilomycin did not inhibit mouse Mphi
      fungistatic activity induced by IFN-gamma. Thus, human Mphi do not require
      phagosomal acidification to kill and degrade Hc yeasts, whereas mouse Mphi do
      require acidification for fungicidal but not fungistatic activity.

PMID- 16424212
TI  - Costimulation requirements for antiviral CD8+ T cells differ for acute and
      persistent phases of polyoma virus infection.
AB  - The requirement for costimulation in antiviral CD8+ T cell responses has been
      actively investigated for acutely resolved viral infections, but it is less
      defined for CD8+ T cell responses to persistent virus infection. Using mouse
      polyoma virus (PyV) as a model of low-level persistent virus infection, we asked
      whether blockade of the CD40 ligand (CD40L) and CD28 costimulatory pathways
      impacts the magnitude and function of the PyV-specific CD8+ T response, as well
      as the humoral response and viral control during acute and persistent phases of
      infection. Costimulation blockade or gene knockout of either CD28 or CD40L
      substantially dampened the magnitude of the acute CD8+ T cell response;
      simultaneous CD28 and CD40L blockade severely depressed the acute T cell
      response, altered the cell surface phenotype of PyV-specific CD8+ T cells,
      decreased PyV VP1-specific serum IgG titers, and resulted in an increase in viral
      DNA levels in multiple organs. CD28 and CD40L costimulation blockade during acute
      infection also diminished the memory PyV-specific CD8+ T cell response and serum
      IgG titer, but control of viral persistence varied between mouse strains and
      among organs. Interestingly, we found that CD28 and CD40L costimulation is
      dispensable for generating and/or maintaining PyV-specific CD8+ T cells during
      persistent infection; however, blockade of CD27 and CD28 costimulation in
      persistently infected mice caused a reduction in PyV-specific CD8+ T cells. Taken
      together, these data indicate that CD8+ T cells primed within the distinct
      microenvironments of acute vs persistent virus infection differ in their
      costimulation requirements.

PMID- 16424214
TI  - Mimicry of apoptotic cells by exposing phosphatidylserine participates in the
      establishment of amastigotes of Leishmania (L) amazonensis in mammalian hosts.
AB  - Signaling through exposed phosphatidylserine (PS) is fundamental for the TGFbeta1
      dependent, noninflammatory phagocytosis of apoptotic cells. This same mechanism
      operates in the internalization of amastigotes of Leishmania (L) amazonensis
      (L(L)a) in a process quoted as apoptotic mimicry. Now we show that the host
      modulates PS exposure by the amastigotes and, as a consequence, BALB/c mice
      derived amastigotes expose significantly more PS than those derived from C57BL/6
      mice. Due to this difference in the density of surface PS molecules, the former
      are significantly more infective than the latter, both in vivo, in F1 (BALB/c x
      C57BL/6) mice, and in vitro, in thioglycollate-derived macrophages from this same
      mouse strain. PS exposure increases with progression of the lesion and reaches
      its maximum value in amastigotes obtained at the time point when the lesion in
      C57BL/6 mice begins to decrease in size and the lesions in BALB/c mice are still
      growing in size. Synthesis of active TGFbeta1, induction of IL-10 message, and
      inhibition of NO synthesis correlate with the amount of surface PS displayed by
      viable (propidium iodide-negative) infective amastigote. Furthermore, we also
      show that, similar to what happens with apoptotic cells, amastigotes of L(L)a are
      internalized by macropinocytosis. This mechanism of internalization is consistent
      with the large phagolysosomes characteristic of L(L)a infection. The intensity of
      macrophage macropinocytic activity is dependent on the amount of surface PS
      displayed by the infecting amastigote.

PMID- 16424213
TI  - Inhibition of TCR signaling by herpes simplex virus.
AB  - T lymphocytes are an essential component of the immune response against HSV
      infection. We previously reported that T cells became functionally impaired or
      inactivated after contacting HSV-infected fibroblasts. In our current study, we
      investigate the mechanisms of inactivation. We report that HSV-infected
      fibroblasts or HSV alone can inactivate T cells by profoundly inhibiting TCR
      signal transduction. Inactivation requires HSV penetration into T cells but not
      de novo transcription or translation. In HSV-inactivated T cells stimulated
      through the TCR, phosphorylation of Zap70 occurs normally. However, TCR signaling
      is inhibited at linker for activation of T cells (LAT) and at steps distal to LAT
      in the TCR signal cascade including inhibition of calcium flux and inhibition of
      multiple MAPK. Inactivation of T cells by HSV leads to the reduced
      phosphorylation of LAT at tyrosine residues critical for TCR signal propagation.
      Treatment of T cells with tyrosine phosphatase inhibitors attenuates inactivation
      by HSV, and stimulus with a mitogen that bypasses LAT phosphorylation overcomes
      inactivation. Our findings elucidate a potentially novel method of viral immune
      evasion that could be exploited to better manage HSV infection, aid in vaccine
      design, or allow targeted manipulation of T cell function.

PMID- 16424216
TI  - Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural
      stereoisomers: assignments of dihydroxy-containing docosatrienes.
AB  - Protectin D1, neuroprotectin D1 when generated by neural cells, is a member of a
      new family of bioactive products generated from docosahexaenoic acid. The
      complete stereochemistry of protectin D1 (10,17S-docosatriene), namely, chirality
      of the carbon-10 alcohol and geometry of the conjugated triene, required for
      bioactivity remained to be assigned. To this end, protectin D1/neuroprotectin D1
      (PD1) generated by human neutrophils during murine peritonitis and by neural
      tissues was separated from natural isomers and subjected to liquid chromatography
      tandem mass spectrometry and gas chromatography-mass spectrometry. Comparisons
      with six 10,17-dihydroxydocosatrienes prepared by total organic and biogenic
      synthesis showed that PD1 from human cells carrying potent bioactivity is 10R,17S
      dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Additional isomers
      identified included trace amounts of Delta15-trans-PD1 (isomer III), 10S,17S
      dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid (isomer IV), and a double
      dioxygenation product 10S,17S-dihydroxy-docosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic
      acid (isomer I), present in exudates. 18O2 labeling showed that 10S,17S-diHDHA
      (isomer I) carried 18O in the carbon-10 position alcohol, indicating sequential
      lipoxygenation, whereas PD1 formation proceeded via an epoxide. PD1 at 10 nM
      attenuated (approximately 50%) human neutrophil transmigration, whereas Delta15
      trans-PD1 was essentially inactive. PD1 was a potent regulator of
      polymorphonuclear leukocyte (PMN) infiltration (approximately 40% at 1 ng/mouse)
      in peritonitis. The rank order at 1- to 10-ng dose was PD1 approximately PD1
      methyl ester >> Delta15-trans-PD1 > 10S,17S-diHDHA (isomer I). 10S,17S-dihydroxy
      docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid (isomer VI) proved > or = PD1 in
      blocking PMN infiltration, but was not a major product of leukocytes. PD1 also
      reduced PMN infiltration after initiation (2 h) of inflammation and was additive
      with resolvin E1. These results indicate that PD1 is a potent stereoselective
      anti-inflammatory molecule.

PMID- 16424215
TI  - Induction of suppressor of cytokine signaling-1 by Toxoplasma gondii contributes
      to immune evasion in macrophages by blocking IFN-gamma signaling.
AB  - Toxoplasma gondii is an intracellular parasite that survives and multiplies in
      professional phagocytes such as macrophages. Therefore, T. gondii has to cope
      with the panel of antimicrobial host immune mechanisms, among which IFN-gamma
      plays a crucial role. We report in this study that in vitro infection of murine
      macrophages with viable, but not with inactivated, parasites results in
      inhibition of IFN-gamma signaling within the infected cells. Thus, infection of
      RAW264.7 macrophages with tachyzoites inhibited IFN-gamma-induced STAT-1 tyrosine
      phosphorylation, mRNA expression of target genes, and secretion of NO. These
      effects were dependent on direct contact of the host cells with living parasites
      and were not due to secreted intermediates. In parallel, we report the induction
      of suppressor of cytokine signaling-1 (SOCS-1), which is a known feedback
      inhibitor of IFN-gamma receptor signaling. SOCS-1 was induced directly by viable
      parasites. SOCS overexpression in macrophages did not affect tachyzoite
      proliferation per se, yet abolished the inhibitory effects of IFN-gamma on
      parasite replication. The inhibitory effects of T. gondii on IFN-gamma were
      diminished in macrophages from SOCS-1-/- mice. The results suggest that induction
      of SOCS proteins within phagocytes due to infection with T. gondii contributes to
      the parasite's immune evasion strategies.

PMID- 16424217
TI  - Fraktalkine produced by airway smooth muscle cells contributes to mast cell
      recruitment in asthma.
AB  - Human airway smooth muscle cells (HASMC) secrete fractalkine (FKN), a chemokine
      the concentration of which is increased in asthmatic patients. HASMC also induce
      mast cell chemotaxis, as a component of asthma inflammation. We therefore
      evaluated the role of smooth muscle-derived FKN in mast cell migration. We
      assessed the capacity of recombinant FKN to induce human mast cell chemotaxis.
      This effect implicates a calcium-independent pathway involving actin
      reorganization and protein kinase C-delta. We found that HASMC constitutively
      produce FKN, the synthesis of which is reinforced upon proinflammatory
      stimulation. Under basal experimental conditions, FKN production by HASMC is not
      sufficient to induce mast cell chemotaxis. However, pretreatment of mast cells
      with the neuropeptide vasoactive intestinal peptide (VIP) increases FKN potency
      to attract mast cells. Since we observed, in asthmatic patients, an increase in
      both FKN and VIP expression by airway smooth muscle and a positive correlation
      between VIP staining and mast cell infiltration of the smooth muscle layer, we
      conclude that HASMC-derived FKN may contribute to mast cell recruitment in
      asthma.

PMID- 16424218
TI  - Corticotropin-releasing factor and the urocortins induce the expression of TLR4
      in macrophages via activation of the transcription factors PU.1 and AP-1.
AB  - Corticotropin-releasing factor (CRF) augments LPS-induced proinflammatory
      cytokine production from macrophages. The aim of the present study was to
      determine the mechanism by which CRF and its related peptides urocortins (UCN) 1
      and 2 affect LPS-induced cytokine production. We examined their role on TLR4
      expression, the signal-transducing receptor of LPS. For this purpose, the murine
      macrophage cell line RAW 264.7 and primary murine peritoneal macrophages were
      used. Exposure of peritoneal macrophages and RAW 264.7 cells to CRF, UCN1, or
      UCN2 up-regulated TLR4 mRNA and protein levels. To study whether that effect
      occurred at the transcriptional level, RAW 264.7 cells were transfected with a
      construct containing the proximal region of the TLR4 promoter linked to the
      luciferase gene. CRF peptides induced activation of the TLR4 promoter, an effect
      abolished upon mutation of a proximal PU.1-binding consensus or upon mutation of
      an AP-1-binding element. Indeed, all three peptides promoted PU.1 binding to the
      proximal PU.1 site and increased DNA-binding activity to the AP-1 site. The
      effects of CRF peptides were inhibited by the CRF2 antagonist anti-sauvagine-30,
      but not by the CRF1 antagonist antalarmin, suggesting that CRF peptides mediated
      the up-regulation of TLR4 via the CRF2 receptor. Finally, CRF peptides blocked
      the inhibitory effect of LPS on TLR4 expression. In conclusion, our data suggest
      that CRF peptides play an important role on macrophage function. They augment the
      effect of LPS by inducing Tlr4 gene expression, through CRF2, via activation of
      the transcription factors PU.1 and AP-1.

PMID- 16424219
TI  - Lipoxin A4 redistributes myosin IIA and Cdc42 in macrophages: implications for
      phagocytosis of apoptotic leukocytes.
AB  - Lipoxins (LXs) are endogenously produced anti-inflammatory agents that modulate
      leukocyte trafficking and stimulate nonphlogistic macrophage phagocytosis of
      apoptotic neutrophils, thereby promoting the resolution of inflammation. Previous
      data suggest a role for altered protein phosphorylation and cytoskeletal
      rearrangement in LX-stimulated phagocytosis but the exact mechanisms remain
      unclear. In this study we examine the effects of LXA4 on the protein
      phosphorylation pattern of THP-1 cells differentiated into a macrophage-like
      phenotype. THP-1 cells stimulated with LXA4 (1 nM) exhibit dephosphorylation of a
      220-kDa protein. Using mass spectrometry, this protein was identified as MYH9, a
      nonmuscle myosin H chain II isoform A, which is involved in cytoskeleton
      rearrangement. THP-1 cells treated with LXA4 adopt a polarized morphology with
      activated Cdc42 localized toward the leading edge and MYH9 localized at the cell
      posterior. Polarized distribution of Cdc42 is associated with Akt/PKB-mediated
      Cdc42 activation. Interestingly, the annexin-derived peptide Ac2-26, a recently
      described agonist for the LXA4 receptor, also stimulates macrophage phagocytosis,
      MYH9 dephosphorylation, and MYH9 redistribution. In addition, we demonstrate that
      LXA4 stimulates the phosphorylation of key polarity organization molecules: Akt,
      protein kinase Czeta, and glycogen synthase kinase-3beta. Inhibition of LXA4
      induced Akt and protein kinase Czeta activity with specific inhibitors prevented
      LXA4-stimulated phagocytosis of both apoptotic polymorphonuclear neutrophils and
      lymphocytes, highlighting a potential use for LXA4 in the treatment of autoimmune
      diseases. Furthermore, phosphorylation and subsequent inactivation of glycogen
      synthase kinase-3beta resulted in an increase in phagocytosis similar to that of
      LXA4. These data highlight an integrated mechanism whereby LXA4 regulates
      phagocytosis through facilitative actin cytoskeleton rearrangement and cell
      polarization.

PMID- 16424220
TI  - Proinflammatory effects of TWEAK/Fn14 interactions in glomerular mesangial cells.
AB  - TNF-like weak inducer of apoptosis, or TWEAK, is a relatively new member of the
      TNF-ligand superfamily. Ligation of the TWEAK receptor Fn14 by TWEAK has
      proinflammatory effects on fibroblasts, synoviocytes, and endothelial cells.
      Several of the TWEAK-inducible cytokines are important in the pathogenesis of
      kidney diseases; however, whether TWEAK can induce a proinflammatory effect on
      kidney cells is not known. We found that murine mesangial cells express cell
      surface TWEAK receptor. TWEAK stimulation of mesangial cells led to a dose
      dependent increase in CCL2/MCP-1, CCL5/RANTES, CXCL10/IFN-gamma-induced protein
      10 kDa, and CXCL1/KC. The induced levels of chemokines were comparable to those
      found following mesangial cell exposure to potent proinflammatory stimuli such as
      TNF-alpha + IL-1beta. CXCL11/interferon-inducible T cell alpha chemoattractant,
      CXCR5, mucosal addressin cell adhesion molecule-1, and VCAM-1 were up-regulated
      by TWEAK as well. TWEAK stimulation of mesangial cells resulted in an increase in
      phosphorylated Ikappa-B, while pretreatment with an Ikappa-B phosphorylation
      inhibitor significantly blocked chemokine induction, implicating activation of
      the NF-kappaB signaling pathway in TWEAK-induced chemokine secretion.
      Importantly, the Fn14-mediated proinflammatory effects of TWEAK on kidney cells
      were confirmed using mesangial cells derived from Fn14-deficient mice and by
      injection in vivo of TWEAK into wild-type vs Fn14-deficient mice. Finally, TWEAK
      induced chemokine secretion was prevented by treatment with novel murine anti
      TWEAK Abs. We conclude that TWEAK induces mesangial cells to secrete
      proinflammatory chemokines, suggesting a prominent role for TWEAK in the
      pathogenesis of renal injury. Our results support Ab inhibition of TWEAK as a
      potential new approach for the treatment of chemokine-dependent inflammatory
      kidney diseases.

PMID- 16424221
TI  - Essential role of MAPK phosphatase-1 in the negative control of innate immune
      responses.
AB  - TLR-induced innate immunity and inflammation are mediated by signaling cascades
      leading to activation of the MAPK family of Ser/Thr protein kinases, including
      p38 MAPK, which controls cytokine release during innate and adoptive immune
      responses. Failure to terminate such inflammatory reactions may lead to
      detrimental systemic effects, including septic shock and autoimmunity. In this
      study, we provide genetic evidence of a critical and nonredundant role of MAPK
      phosphatase (MKP)-1 in the negative control of MAPK-regulated inflammatory
      reactions in vivo. MKP-1-/- mice are hyperresponsive to low-dose LPS-induced
      toxicity and exhibit significantly increased serum TNF-alpha, IL-6, IL-12, MCP-1,
      IFN-gamma, and IL-10 levels after systemic administration of LPS. Furthermore,
      absence of MKP-1 increases systemic levels of proinflammatory cytokines and
      exacerbates disease development in a mouse model of rheumatoid arthritis. When
      activated through TLR2, TLR3, TLR4, TLR5, and TLR9, bone marrow-derived MKP-1-/-
      macrophages exhibit increased cytokine production and elevated expression of the
      differentiation markers B7.2 (CD86) and CD40. MKP-1-deficient macrophages also
      show enhanced constitutive and TLR-induced activation of p38 MAPK. Based on these
      findings, we propose that MKP-1 is an essential component of the intracellular
      homeostasis that controls the threshold and magnitude of p38 MAPK activation in
      macrophages, and inflammatory conditions accentuate the significance of this
      regulatory function.

PMID- 16424222
TI  - In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and
      psoriasis lesions: enhanced expression in psoriatic skin.
AB  - Keratinocytes contribute to cutaneous immune responses through the expression of
      cytokines. We investigated whether human keratinocytes can express IL-23, a newly
      defined IFN-gamma-inducing cytokine composed of a unique p19 subunit and a p40
      subunit shared with IL-12. Cultured keratinocytes from normal and lesional
      psoriatic skin were found to express constitutively mRNA for both subunits of IL
      23. Low but significant levels of the heterodimeric IL-23 protein could be
      detected in cell lysates and supernatants from stimulated keratinocytes by
      immunoblotting and ELISA. Functional analysis showed that these low levels of
      keratinocyte-derived IL-23 were sufficient to enhance the IFN-gamma production by
      memory T cells. Immunostaining of skin sections confirmed expression of both
      subunits of IL-23 by keratinocytes in situ and also revealed expression of this
      cytokine in the dermal compartment. IL-23 expression was significantly higher in
      psoriatic lesional skin, compared with normal and psoriatic nonlesional skin. The
      immunostained preparations of cultured cells and IL-23 levels in culture
      supernatants did not show any difference between normal and psoriatic
      keratinocytes indicating no intrinsic aberration of IL-23 expression in
      keratinocytes from psoriatic skin. Double staining of cytospin preparations
      demonstrated that IL-23 p19 is also expressed by epidermal Langerhans cells,
      dermal dendritic cells, and macrophages. Psoriasis is a chronic inflammatory skin
      disease mediated by IFN-gamma-expressing type 1 memory T cells. As IL-23 is
      important to activate memory T cells to produce IFN-gamma, its augmented
      expression of IL-23 by keratinocytes and cutaneous APC may contribute to the
      perpetuation of the inflammation process in this disease.

PMID- 16424223
TI  - Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to
      airway injury.
AB  - Recipient airway epithelial cells are found in human sex-mismatched lung
      transplants, implying that circulating progenitor epithelial cells contribute to
      the repair of the airway epithelium. Markers of circulating progenitor epithelial
      cells and mechanisms for their trafficking remain to be elucidated. We
      demonstrate that a population of progenitor epithelial cells exists in the bone
      marrow and the circulation of mice that is positive for the early epithelial
      marker cytokeratin 5 (CK5) and the chemokine receptor CXCR4. We used a mouse
      model of sex-mismatched tracheal transplantation and found that CK5+ circulating
      progenitor epithelial cells contribute to re-epithelialization of the airway and
      re-establishment of the pseudostratified epithelium. The presence of CXCL12 in
      tracheal transplants provided a mechanism for CXCR4+ circulating progenitor
      epithelial cell recruitment to the airway. Depletion of CXCL12 resulted in the
      epithelium defaulting to squamous metaplasia, which was derived solely from the
      resident tissue progenitor epithelial cells. Our findings demonstrate that
      CK5+CXCR4+ cells are markers of circulating progenitor epithelial cells in the
      bone marrow and circulation and that CXCR4/CXCL12-mediated recruitment of
      circulating progenitor epithelial cells is necessary for the re-establishment of
      a normal pseudostratified epithelium after airway injury. These findings support
      a novel paradigm for the development of squamous metaplasia of the airway
      epithelium and for developing therapeutic strategies for circulating progenitor
      epithelial cells in airway diseases.

PMID- 16424224
TI  - Suppression of discoidin domain receptor 1 by RNA interference attenuates lung
      inflammation.
AB  - Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is
      collagen. Recently, we have reported the association of DDR1 in the cytokine
      production of human leukocytes in in vitro and in vivo expression in idiopathic
      pulmonary fibrosis. However, its role in in vivo inflammation has not been fully
      elucidated. Small interference RNA (siRNA) can induce specific suppression of in
      vitro and in vivo gene expression. In this study, using a bleomycin-induced
      pulmonary fibrosis mouse model, we administered siRNA against DDR1 transnasally
      and evaluated histological changes, cytokine expression, and signaling molecule
      activation in the lungs. Histologically, siRNA against DDR1 successfully reduced
      in vivo DDR1 expression and attenuated bleomycin-induced infiltration of
      inflammatory cells. Furthermore, it significantly reduced inflammatory cell
      counts and concentrations of cytokines such as MCP-1, MIP-1alpha, and MIP-2 in
      bronchoalveolar lavage fluid. Subsequently, bleomycin-induced up-regulation of
      TGF-beta in bronchoalveolar lavage fluid was significantly inhibited, and
      collagen deposition in the lungs was reduced. Furthermore, siRNA against DDR1
      significantly inhibited bleomycin-induced P38 MAPK activation in the lungs.
      Considered together, we propose that DDR1 contributes to the development of
      bleomycin-induced pulmonary inflammation and fibrosis.

PMID- 16424225
TI  - Deletion of TLR3 alters the pulmonary immune environment and mucus production
      during respiratory syncytial virus infection.
AB  - The detection of a viral infection by pattern recognition receptors (PAMPs) is an
      integral part of antiviral immunity. In these studies we have investigated the
      role of TLR3, which recognizes dsRNA, in Respiratory Syncytial virus (RSV)
      infection using B6 background mice with a TLR3 deletion. Although we observed no
      changes in viral growth, we did find that TLR3-/- mice demonstrated significant
      increases in mucus production in the airways of RSV-infected mice. The
      qualitative assessment was observed by examining differentially stained lungs,
      followed by immunohistochemical staining for gob5, a mucus-associated protein.
      The histopathologic observations were verified using quantitative gene expression
      analyses examining gob5 gene expression. Changes in pulmonary mucus production
      were accompanied by an increase in pulmonary IL-13 as well as IL-5 expression and
      eosinophils in the airways of TLR3-/- mice. Examining leukocytes in the airway
      indicated an accumulation of eosinophils in TLR3-/- mice, but not wild-type mice,
      after RSV infection. Isolated lung draining lymph node cells from TLR3-/- mice
      produced significant increases in Th2-type cytokines, IL-5, and IL-13, compared
      with wild-type TLR3+/+ mice only after RSV infection. To demonstrate a causative
      link, we depleted TLR3-/- mice of IL-13 during RSV infection and found that mucus
      and gob5 expression in the lungs was attenuated. Together, these studies
      highlight that although TLR3 may not be required for viral clearance, it is
      necessary to maintain the proper immune environment in the lung to avoid
      developing pathologic symptoms of disease.

PMID- 16424226
TI  - Inhibition of chronic airway inflammation and remodeling by galectin-3 gene
      therapy in a murine model.
AB  - We previously demonstrated that treatment of acute asthmatic rats with gene
      therapy using plasmid-encoding Galectin-3 (Gal-3) resulted in an improvement of
      cellular and functional respiratory parameters. The next question that we wanted
      to clarify was if in a chronic situation where the treated animal continues to
      inhale the Ag, does this procedure prevent the chronicity and the remodeling?
      Chronic inflammation was induced by intranasal administration of OVA over a
      period of 12 wk. In the treated group, the Gal-3 gene was introduced by
      intranasal instillation in 50 mul of plasmid-encoding Gal-3. Noninvasive airway
      responsiveness to methacholine was tested at different times. Cells were obtained
      by bronchoalveolar lavage and used for RNA extraction and cytometric studies.
      Eosinophils were counted in blood and bronchoalveolar lavage fluid. Real-time PCR
      was used to measure Gal-3 and cytokine mRNA expression in lung. Lungs were
      paraffined and histologic analyses were performed (H&E, periodic acid-Schiff, and
      Masson Trichrome stain). Our results showed that 12 wk after the first intranasal
      Ag instillation in chronically asthmatic mice, treatment with the Gal-3 gene led
      to an improvement in the eosinophil count and the normalization of
      hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an
      improvement in mucus secretion and subepithelial fibrosis in the chronically
      asthmatic mice, with a quantitatively measured reduction in lung collagen, a
      prominent feature of airway remodeling. Plasmid-encoding Gal-3 acts as a novel
      treatment for chronic asthma in mice producing nearly complete blockade of Ag
      responses with respect to eosinophil airway accumulation, airway
      hyperresponsiveness, and remodeling.

PMID- 16424228
TI  - Effacing of the T cell compartment by cardiac transplantation in infancy.
AB  - For cardiac transplantation in infants, T cells are depleted and the thymus is
      removed. These manipulations should cause profound defects in the T cell
      compartment. To test this concept, 20 subjects who underwent cardiac
      transplantation in infancy and healthy age-matched subjects were studied. The
      number of T cells in the blood was nearly normal in all subjects 1-10 years after
      surgery. However, newly generated T cells were undetectable in 10 recipients and
      10-fold less than controls in 10, suggesting absence of thymic function. TCRbeta
      chain diversity, measured by a novel technique, was approximately 100-fold lower
      than controls. T cell function, deduced from levels of human herpesvirus 7 and
      response to hepatitis B immunization, were notably impaired. Yet cardiac
      transplant recipients were generally free of opportunistic infections. Our
      findings demonstrate a novel approach to measuring lymphocyte diversity and
      suggest that understanding how these subjects resist infection could yield
      important insights into immune fitness.

PMID- 16424229
TI  - Identification of an epitope within human integrin alpha 6 subunit for the
      binding of autoantibody and its role in basement membrane separation in oral
      pemphigoid.
AB  - Oral pemphigoid (OP) is a rare chronic autoimmune disease characterized by
      blisters and erosive lesions in the oral mucosa. We identified an epitope for the
      binding of OP autoantibodies within the integrin alpha6 subunit, by cloning four
      overlapping fragments (A, B, C, and D). Immunoperoxidase studies demonstrated
      that all of the fragments were present in the oral mucosa. Sera of 20 patients
      with active OP were studied. All sera bound to integrin alpha6 in DU145 cell
      lysate by immunoprecipitation and immunoblot assay. The same sera bound only to
      fragment A and its subfragment A2 on an immunoblot assay. The specificity of the
      binding was further characterized by blocking and cross-absorption studies. A 14
      aa synthetic peptide A2.1, within fragment A2, bound to all the test sera. The
      sera in this study bound to only one epitope. Controls were sera samples from 10
      healthy volunteers and 40 patients with other variants of mucous membrane
      pemphigoid and mAb GoH3 and BQ16 to integrin alpha6. Control sera did not bind to
      the full-length integrin alpha6 subunit nor any of the cloned fragments. The OP
      patient sera and immunoaffinity-purified OP sera, rabbit antisera against
      fragments A and A2, and mAb GoH3 produced basement membrane separation of oral
      mucosa in organ culture. This study identifies a peptide within the extracellular
      domain of integrin alpha6 molecule, to which Abs in the sera from patients with
      OP bind, and which may play an important role in the pathogenesis of OP.

PMID- 16424227
TI  - Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the
      multiple sclerosis-associated HLA-DR2 haplotype.
AB  - The three HLA class II alleles of the DR2 haplotype, DRB1*1501, DRB5*0101, and
      DQB1*0602, are in strong linkage disequilibrium and confer most of the genetic
      risk to multiple sclerosis. Functional redundancy in Ag presentation by these
      class II molecules would allow recognition by a single TCR of identical peptides
      with the different restriction elements, facilitating T cell activation and
      providing one explanation how a disease-associated HLA haplotype could be linked
      to a CD4+ T cell-mediated autoimmune disease. Using combinatorial peptide
      libraries and B cell lines expressing single HLA-DR/DQ molecules, we show that
      two of five in vivo-expanded and likely disease-relevant, cross-reactive
      cerebrospinal fluid-infiltrating T cell clones use multiple disease-associated
      HLA class II molecules as restriction elements. One of these T cell clones
      recognizes >30 identical foreign and human peptides using all DR and DQ molecules
      of the multiple sclerosis-associated DR2 haplotype. A T cell signaling machinery
      tuned for efficient responses to weak ligands together with structural features
      of the TCR-HLA/peptide complex result in this promiscuous HLA class II
      restriction.

PMID- 16424230
TI  - TLR9 activation is defective in common variable immune deficiency.
AB  - Common variable immune deficiency (CVID) is a primary immune deficiency
      characterized by low levels of serum immune globulins, lack of Ab, and reduced
      numbers of CD27+ memory B cells. Although T, B, and dendritic cell defects have
      been described, for the great majority, genetic causes have not been identified.
      In these experiments, we investigated B cell and plasmacytoid dendritic cell
      activation induced via TLR9, an intracellular recognition receptor that detects
      DNA-containing CpG motifs from viruses and bacteria. CpG-DNA activates normal B
      cells by the constitutively expressed TLR9, resulting in cytokine secretion, IgG
      class switch, immune globulin production, and potentially, the preservation of
      long-lived memory B cells. We found that CpG-DNA did not up-regulate expression
      of CD86 on CVID B cells, even when costimulated by the BCR, or induce production
      of IL-6 or IL-10 as it does for normal B cells. TLR9, found intracytoplasmically
      and on the surface of oligodeoxynucleotide-activated normal B cells, was
      deficient in CVID B cells, as was TLR9 mRNA. TLR9 B cell defects were not related
      to proportions of CD27+ memory B cells. CpG-activated CVID plasmacytoid dendritic
      cells did not produce IFN-alpha in normal amounts, even though these cells
      contained abundant intracytoplasmic TLR9. No mutations or polymorphisms of TLR9
      were found. These data show that there are broad TLR9 activation defects in CVID
      which would prevent CpG-DNA-initiated innate immune responses; these defects may
      lead to impaired responses of plasmacytoid dendritic cells and loss of B cell
      function.

PMID- 16424231
TI  - Allelic variation in key peptide-binding pockets discriminates between closely
      related diabetes-protective and diabetes-susceptible HLA-DQB1*06 alleles.
AB  - HLA-DQA1*0102-DQB1*0602 is associated with protection against type 1 diabetes
      (T1D). A similar allele, HLA-DQA1*0102-DQB1*0604, contributes to T1D
      susceptibility in certain populations but differs only at seven amino acids from
      HLA-DQA1*0102-DQB1*0602. Five of these polymorphisms are found within the peptide
      binding groove, suggesting that differences in peptide binding contribute to the
      mechanism of their association with T1D. In this study, we determine the peptide
      binding motif for HLA-DQA1*0102-DQB1*0604 allelic protein (DQ0604) in comparison
      to the established HLA-DQA1*0102-DQB1*0602 (DQ0602) motif using binding assays
      with model peptides from T1D autoantigens and homology modeling using the
      coordinates of the DQ0602-hypocretin 1-13 crystal structure. The peptide binding
      preferences were deduced with a peptide from insulin that bound both with a 2- to
      3-fold difference in avidity using the same amino acids in the peptide as
      anchors. Peptide binding differences directly influenced by the polymorphisms in
      or nearby pockets 1, 6, and 9 were observed. In pocket 1, DQ0604 was better able
      to accommodate aromatic residues due to the beta86 and beta87 polymorphisms. A
      negatively charged amino acid was preferred by DQ0604 in pocket 6 due to the
      positively charged beta30His. In pocket 9, DQ0604 preferred aromatic amino acids
      due to the beta9 and beta30 polymorphisms and had low tolerance of acidic
      residues. beta57Val in DQ0604 functions differently than beta57Ala, in that it
      pushes alpha76Arg outside of the pocket, preventing the formation of a salt
      bridge with an acidic amino acid in the peptide. This study furthers our
      understanding of the structure-function relationships of MHC class II
      polymorphisms.

PMID- 16424232
TI  - Predicting tumor outcome following cancer vaccination by monitoring quantitative
      and qualitative CD8+ T cell parameters.
AB  - Identification of reliable surrogate predictors for evaluation of cancer vaccine
      efficacy is a critical issue in immunotherapy. We analyzed quantitative and
      qualitative CD8+ T cell parameters in a large pool of BALB/c mice that were DNA
      vaccinated against P1A self tumor-specific Ag. After immunization, mice were
      splenectomized and kept alive for a subsequent tumor challenge to correlate
      results of immune monitoring assays with tumor regression or progression in each
      individual animal, and to assess the prognostic value of the assays. The
      parameters tested were 1) percentage of in vivo vaccine-induced tumor-specific
      CD8+ T cells; 2) results of ELISPOT tests from fresh splenocytes; 3) percentage
      of tumor-specific CD8+ T cells in culture after in vitro restimulation; 4) in
      vitro increase of tumor-specific CD8+ T cell population expressed as fold of
      expansion; and 5) antitumor lytic activity of restimulated cultures. Except for
      the ELISPOT assay, each parameter tested was shown by univariate statistical
      analysis to correlate with tumor regression. However, multivariate analysis
      revealed that only in vitro percentage of Ag-specific CD8+ T cells was an
      independent prognostic factor that predicted tumor outcome. These findings should
      be considered in the design of new immune monitoring systems used in cancer
      immunotherapy studies.

PMID- 16424233
TI  - Pretreatment intracerebral and peripheral blood immune responses in Vietnamese
      adults with tuberculous meningitis: diagnostic value and relationship to disease
      severity and outcome.
AB  - Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both
      intracerebral and peripheral blood immune responses may be relevant to
      pathogenesis, diagnosis, and outcome. In this study, the relationship between
      pretreatment host response, disease phenotype, and outcome in Vietnamese adults
      with TBM was examined. Before treatment, peripheral blood IFN-gamma ELISPOT
      responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified
      protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal
      fluid IL-6 concentrations at presentation were independently associated with
      severe disease presentation, suggesting an immunological correlate of
      neurological damage before treatment. Surprisingly however, elevated
      cerebrospinal fluid inflammatory cytokines were not associated with death or
      disability in HIV-negative TBM patients at presentation. HIV coinfection
      attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal
      fluid IFN-gamma concentrations were independently associated with death in HIV
      positive TBM patients, implying that IFN-gamma contributes to immunity and
      survival. Collectively, these results reveal the effect of HIV coinfection on the
      pathogenesis of TBM and suggest that intracerebral immune responses, at least in
      HIV-negative cases, may not be as intimately associated with disease outcome as
      previously thought.

PMID- 16424235
TI  - Chronic pancreatitis: MRCP versus ERCP for quantitative caliber measurement and
      qualitative evaluation.
AB  - PURPOSE: To retrospectively compare-in patients with chronic pancreatitis
      magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde
      cholangiopancreatography (ERCP) for measurement of main pancreatic duct (MPD)
      diameter by using area intensity measurement (AIM) at MRCP and full width at half
      maximum (FWHM) at ERCP and to retrospectively determine the accuracy of MRCP for
      depiction of pathologic changes by using ERCP as the reference standard.
      MATERIALS AND METHODS: The institutional review board approved this study and
      waived the need to obtain informed consent. Both MRCP and ERCP were performed in
      24 patients with chronic pancreatitis (21 men, three women; mean age, 54 years +/
      14 [standard deviation]). The diameter of the MPD was determined by using both
      methods at the same sites in the head, body, and tail of the pancreas. MRCP and
      ERCP measurements involved AIM and FWHM techniques, respectively. For qualitative
      evaluation, visualization of the MPD and pathologic findings was also examined by
      using both methods. Paired t and Wilcoxon matched-pair signed rank tests were
      performed for the quantitative and qualitative evaluations, respectively.
      RESULTS: The mean diameter of the MPD at ERCP was 1.5 times larger, on average,
      than that at MRCP; differences were statistically significant for each segment,
      as well as for the entire duct system. For qualitative evaluation, MRCP tended to
      be superior to ERCP for delineation of the MPD. Overall sensitivity, specificity,
      and accuracy values of MRCP for delineating pathologic pancreatic changes were
      88% (87 of 99), 98% (44 of 45), and 91% (131 of 144), respectively. CONCLUSION:
      Use of ERCP tends to result in overestimation of the caliber of the MPD. MRCP can
      enable accurate evaluation of the condition of the pancreatic duct and its
      changes in patients with chronic pancreatitis.

PMID- 16424234
TI  - Autoreactive T and B cells from bullous pemphigoid (BP) patients recognize
      epitopes clustered in distinct regions of BP180 and BP230.
AB  - Bullous pemphigoid (BP) is a well-characterized model of autoantibody-mediated
      autoimmunity, which presumably depends on autoreactive Th cells that promote the
      activation of autoreactive B cells. The two major autoantigens of BP are BP180
      and BP230, two components of dermoepidermal adhesion complexes. Both,
      autoreactive Th cell responses and autoantibody profiles were characterized in 35
      patients with acute onset BP using BP180 and BP230 proteins. Our findings
      indicate the following: 1) autoreactive Th cells recognized epitopes within the
      NH2-terminal (77.1%), COOH-terminal (65.7%), and central portion (57.1%) of the
      BP180 ectodomain; 2) IgG autoantibodies were found to exhibit similar or
      identical reactivity against the NH2-terminal (82.8%), COOH-terminal (77.1%), and
      central portion (37.1%) of the BP180 ectodomain; 3) T and B cell reactivity with
      the NH2-terminal portion of the BP180 ectodomain was associated with extensive
      BP, whereas the central portion was more frequently recognized in limited BP; 4)
      only 7 of 16 (43.7%) and 6 of 16 (37.5%) BP patients showed a Th cellular
      response against the COOH- and NH2-terminal regions of BP230, respectively,
      whereas 5) IgG reactivity against the COOH- and NH2-termini of BP230 was detected
      in 5 of 16 (31.3%) and 6 of 16 (37.5%) patients, respectively. These results
      demonstrate that Th and B cell reactivities against BP180, are, in contrast to
      BP230 reactivity, almost constantly detectable in BP patients, and differential
      epitope recognition of BP180 seems to be associated with distinct clinical
      severity. These observations support the concept that BP180, but not BP230, is
      the primary autoantigen of BP critical for disease development.

PMID- 16424236
TI  - Organized breast screening programs in Canada: effect of radiologist reading
      volumes on outcomes.
AB  - PURPOSE: To examine retrospectively the relationship between radiologist
      screening program reading volumes and interpretation results. MATERIALS AND
      METHODS: This research project was reviewed by the University of British Columbia
      Research Ethics Board. Informed patient consent was not required. Data were
      requested from Canadian provincial screening programs for the period 1988-2000.
      Cancer detection rates, abnormal interpretation rates, and positive predictive
      values (PPVs) were calculated for individual radiologists in those programs.
      Multivariate Poisson mixed regression models were used to examine the effect of
      patient age, screening examination sequence (first or subsequent screening
      examination), province, radiologist reading volume, and interradiologist
      differences on cancer detection rate, abnormal interpretation rate, and PPV.
      RESULTS: The results of the interpretation of 1406678 screening mammograms by 304
      radiologists from seven provincial programs were analyzed. Cancer detection rate,
      abnormal interpretation rate, and PPV all varied according to age of woman
      screened and screening sequence and across the sample of radiologists. None of
      the rates varied by province. Neither the cancer detection rate nor the abnormal
      interpretation rate varied by reading volume, but the average PPV was increased
      by 34% for volumes over 2000 mammograms versus volumes of 480-699 mammograms per
      year. There was no evidence that the magnitude of variability around the average,
      for radiologists reading the same volume of mammograms, varied across different
      volume groups for any of the outcome measures. CONCLUSION: Cancer detection did
      not vary with reading volume. The average PPV for individual radiologists
      increased as reading volume rose up to 2000 mammograms per year; it stabilized at
      higher volumes.

PMID- 16424237
TI  - Papillary lesions of the breast at percutaneous core-needle biopsy.
AB  - PURPOSE: To retrospectively review the imaging and histologic findings in
      patients in whom a benign papillary lesion was diagnosed at core-needle breast
      biopsy. MATERIALS AND METHODS: This retrospective study was approved by the
      institutional review board at each institution; patient consent was not required.
      The study was HIPAA compliant. The authors reviewed the findings from 42 patients
      (age range, 26-76 years; mean age, 54.3 years) with 43 benign papillary lesions
      diagnosed at core-needle biopsy. Thirty-six (84%) of the 43 lesions were
      surgically excised, and seven (16%) were followed up with long-term imaging. The
      authors assessed the radiographic findings, the histologic findings at core
      needle biopsy, and the findings at subsequent surgical excision or imaging follow
      up. Statistical analysis was performed on a per-patient basis and included the
      Blyth-Still-Casella procedure to construct exact 95% confidence intervals (CIs)
      and the Fisher exact test. RESULTS: At core-needle biopsy, lesions were diagnosed
      as papilloma (n = 29), sclerosing papilloma (n = 8), and benign papillary lesions
      not otherwise specified (n = 6). For the 36 lesions that were surgically excised,
      histologic follow-up showed no residual lesion in 10, intraductal papilloma in
      14, intraductal papillomatosis in two, papilloma with adjacent foci of atypical
      ductal hyperplasia (ADH) in eight, and well-differentiated papillary ductal
      carcinoma in situ (DCIS) in two. Mammographic follow-up in the remaining seven
      lesions revealed stable calcifications in five (at 28-55 months) and no residual
      lesion in two (at 26-29 months). In nine of the 42 patients (21%), the diagnosis
      was upgraded to either ADH or DCIS (exact two-sided 95% CI = 11.4%, 36.4%).
      CONCLUSION: The results strongly suggest that papillary lesions diagnosed as
      benign at core-needle biopsy should be surgically excised because a substantial
      number of lesions were upgraded to ADH and DCIS at excision.

PMID- 16424238
TI  - Preoperative grading of gliomas by using metabolite quantification with high
      spatial-resolution proton MR spectroscopic imaging.
AB  - PURPOSE: To evaluate proton magnetic resonance (MR) spectroscopic imaging with
      high spatial resolution for preoperative grading of suspected World Health
      Organization grades II and III gliomas. MATERIALS AND METHODS: Institutional
      ethics committee approval and informed consent were obtained for control subjects
      but were not required for the retrospective component involving patients. Twenty
      six patients (10 women, 16 men; mean age, 37.5 years) suspected of having gliomas
      and 26 age- and sex-matched control subjects underwent proton MR spectroscopy.
      Absolute metabolite concentrations for choline-containing compounds (Cho),
      creatine (Cr), and N-acetylaspartate (NAA)-N-acetylaspartylglutamate (total NAA
      [tNAA]) were calculated by using a user-independent spectral fit program.
      Metabolic maps of Cho/tNAA ratios were calculated, segmented, and used for MR
      spectroszpcopy-guided stereotactic brain biopsy. Two-sided paired Student t tests
      were used to test for statistical significance. RESULTS: Significantly lower Cho
      levels (P = .002) and higher tNAA levels (P = .010) were found in grade II tumors
      (n = 9) compared with grade III tumors (n = 17). The average Cho/tNAA ratio over
      the voxels in the tumor center showed a distinct difference (P < .001) between
      grade II and III gliomas at a threshold of 0.8 (with ratios <0.8 for grade II).
      The maximum Cr concentration in the tumor showed a clear-cut threshold between
      grade III oligodendrogliomas and oligoastrocytomas (Cr level, <7 mmol/L) and
      grade III astrocytomas (Cr level, >7 mmol/L; P = .020). Comparison between the
      histopathologic findings from the MR spectroscopy-guided biopsy samples (76
      biopsies from 26 patients) and molar metabolite values in corresponding voxels
      located at the biopsy sampling points showed a negative linear correlation for
      tNAA (r = -0.905) and a positive exponential correlation for Cho (r = 0.769) and
      Cho/tNAA (r = 0.885). CONCLUSION: Proton MR spectroscopic imaging with high
      spatial resolution allows preoperative grading of gliomas.

PMID- 16424239
TI  - Human myocardium: single-breath-hold MR T1 mapping with high spatial resolution-
      reproducibility study.
AB  - A prospective study approved by the local ethics committee was performed to
      establish the normal range and reproducibility of myocardial T1 values as
      assessed with single-breath-hold T1 mapping with high spatial resolution. With a
      1.5-T magnetic resonance (MR) imaging system, baseline and contrast material
      enhanced modified Look-Locker inversion recovery, or MOLLI, imaging was performed
      in 15 healthy volunteers who had given written informed consent. Image quality
      scores and myocardial T1 values were derived for standard short-axis segments and
      sections. Results were compared with those from a second MR imaging study
      performed on the same day (baseline only) and those from a third study performed
      on a different day (baseline and contrast enhanced; eight volunteers). Intra- and
      interobserver agreement were determined. Myocardial T1 maps were obtained rapidly
      in a reproducible fashion. A normal range for baseline and postcontrast
      myocardial T1 was established (baseline mean T1 in short-axis sections, 980 msec
      +/- 53 [standard deviation]; 95% confidence interval: 964, 997; number of
      sections, 43). This technique could enable direct quantification of changes in
      tissue characteristics in ischemic and inflammatory myocardial diseases.

PMID- 16424240
TI  - Radiation doses from venous access procedures.
AB  - PURPOSE: To retrospectively analyze radiation dose data for six common venous
      access procedures. MATERIALS AND METHODS: Institutional review board approval was
      obtained for this HIPAA-compliant study; informed consent was not required. Data
      review was limited to a quality assurance database. Patient medical records were
      not reviewed. We retrospectively analyzed radiation dose data from a prospective
      quality assurance program. Dose data were analyzed for 1010 instances of six
      different venous access placement procedures performed between February 1998 and
      July 2004. Radiation dose measurements were generated automatically by the
      interventional fluoroscopy units and were recorded at the conclusion of each
      procedure. Descriptive and summary statistical analyses were performed to
      determine median, minimum, and maximum values of radiation dose for each
      procedure. A P value of less than .05 indicated a significant difference. Because
      the data distribution was highly skewed, logarithmic transformation was
      performed. Dose data for four different venous access procedures (excluding chest
      port placement and peripherally inserted central catheter placement) were
      compared with a one-way analysis of variance. Pairwise comparisons with the Tukey
      honestly significant difference test were subsequently performed for each
      analogue where analysis of variance demonstrated a significant result. RESULTS:
      No procedure yielded a cumulative dose of more than 950 mGy or a peak skin dose
      of more than 760 mGy. The highest mean cumulative dose (ie, 88 mGy), mean dose
      area product (ie, 873 cGy . cm(2)), and mean peak skin dose (ie, 43 mGy) were
      observed for tunneled dialysis catheter placements. Significant differences in
      dose were observed for tunneled catheter placement versus nontunneled catheter
      placement (<.001 to .027). No significant differences in dose were observed for
      larger-diameter versus smaller-diameter catheters. CONCLUSION: Radiation doses
      from venous access procedures are low. Even extreme outlier cases are unlikely to
      produce doses high enough to cause skin effects, especially when knowledgeable
      operators using well-calibrated equipment perform the procedures.

PMID- 16424242
TI  - Pulmonary emphysema: objective quantification at multi-detector row CT-
      comparison with macroscopic and microscopic morphometry.
AB  - PURPOSE: To prospectively compare pulmonary function tests and helical computed
      tomographic (CT) indexes for quantifying pulmonary emphysema with macroscopic and
      microscopic morphometry. MATERIALS AND METHODS: The investigation was approved by
      the local ethics committee, and written informed consent was obtained from
      patients. Multi-detector row CT of the thorax was performed with simultaneous
      acquisition of four 1-mm sections in 80 patients (57 men, 23 women; age range, 38
      79 years) referred for surgical resection of lung cancer. From the raw data, 1.25
      mm-thick sections were reconstructed at 10-mm intervals. Relative areas of lung
      with attenuation coefficients lower than nine thresholds and eight percentiles of
      the distribution of attenuation coefficients were calculated. Relative areas and
      percentiles were compared with areas found macroscopically to have emphysema and
      with two microscopic indexes assessed on resected specimens. Pulmonary function
      tests were measured 24-48 hours before surgery. Spearman correlation coefficients
      were calculated between each set of CT data obtained with the nine tested
      thresholds and eight percentiles with macroscopic and microscopic measurements.
      RESULTS: For relative lung areas, the strongest correlation with macroscopy was
      observed with a threshold of -970 HU (r = 0.543, P < .001) and that with
      microscopy was observed at -960 and -970 HU, depending on the index considered (r
      = 0.592, P < .001 and r = -0.546, P < .001, respectively). For percentiles, 1st
      percentile showed the strongest correlation with both macroscopy (r = -0.463, P <
      .001) and microscopy (r = -0.573, P < .001; and r = 0.523, P < .001 for each
      microscopic measurement). Forced expiratory volume in 1 second and vital capacity
      ratio, diffusing capacity of lung for carbon monoxide, and each of the three CT
      indexes were complementary to predict microscopic indexes. CONCLUSION: Relative
      lung areas with attenuation coefficients lower than -960 or -970 HU and 1st
      percentile are valid indexes to quantify pulmonary emphysema on multi-detector
      row CT scans.

PMID- 16424241
TI  - Superior semicircular canal dehiscence: oblique reformatted CT images for
      diagnosis.
AB  - PURPOSE: To retrospectively determine, by using thin-section multi-detector row
      computed tomography (CT), whether additional reformations in the planes of
      Stenver and Poschl change the diagnostic interpretation for superior semicircular
      canal dehiscence (SSCD) when compared with the diagnostic interpretation of
      standard coronal reformations for SSCD. MATERIALS AND METHODS: Institutional
      review board approval was obtained, patient anonymity was maintained, and the
      study was HIPAA compliant. Twenty-seven patients (17 men, 10 women; average age,
      45 years; range, 19-72 years) suspected of having SSCD who underwent temporal
      bone multi-detector row CT were retrospectively identified from electronic
      medical records. An additional 27 control subjects (nine men, 18 women; average
      age, 50 years; range, 18-87 years), who underwent temporal bone multi-detector
      row CT for other reasons, were retrospectively selected from the same period. Two
      neuroradiologists with certificates of added qualification, one with 5 years and
      one with 9 years of experience interpreting temporal bone CT images,
      independently reviewed the 108 temporal bones twice. One review was restricted to
      transverse images and coronal reformations. The other review used transverse
      images, coronal reformations, and oblique reformations in the planes of Stenver
      and Poschl. The observers were blinded to clinical history, and the two reviews
      took place 3 months apart to avoid recall bias. The primary outcome measure was
      the intraobserver discordance rate between the two reviews. kappa Statistics were
      used to evaluate both intraobserver and interobserver variability. RESULTS:
      Observer 1 diagnosed SSCD in 25 of 108 (23%) temporal bones and had no
      discordances between the two reviews. Observer 2 diagnosed SSCD in 21 of 108
      (19%) temporal bones and had one intraobserver discordance. After a post hoc
      consensus review of this one discordance, the radiologic diagnosis remained
      equivocal. The discordance involved the right temporal bone of a patient
      suspected of having SSCD in the left temporal bone, so no clinical follow-up was
      available. CONCLUSION: Coronal reformations from multi-detector row CT of the
      temporal bone are sufficient for the evaluation of SSCD. Additional reformations
      in the planes of Stenver and Poschl do not change the radiologic diagnosis and
      may be reserved for equivocal or confusing cases.

PMID- 16424243
TI  - Subchondral bone marrow edema in patients with degeneration of the articular
      cartilage of the knee joint.
AB  - PURPOSE: To retrospectively determine at magnetic resonance (MR) imaging the
      prevalence of subchondral bone marrow edema beneath arthroscopically proved
      articular cartilage defects. MATERIALS AND METHODS: The study was performed in
      compliance with HIPAA regulations, and a waiver of informed consent was obtained
      from the institutional review board before the study was performed. The study
      consisted of 132 patients (70 men, 62 women; average age, 53 years) with
      articular cartilage defects of the knee joint who underwent MR imaging of the
      knee and subsequent arthroscopic knee surgery. At the time of arthroscopy, each
      articular cartilage lesion was graded by using the Noyes classification system.
      MR examinations were retrospectively reviewed to determine the size, depth, and
      location of subchondral bone marrow edema without knowledge of the arthroscopic
      findings. Pairwise Fisher exact tests and two-sample t tests were used to
      correlate MR imaging findings of subchondral bone marrow edema with the
      arthroscopic grade of articular cartilage degeneration. RESULTS: Subchondral bone
      marrow edema was seen beneath 105 (19%) of 554 articular cartilage defects
      identified at arthroscopy. It was not observed beneath any of the six grade 1
      cartilage defects but was observed beneath eight (4.9%) of 163 grade 2A defects,
      40 (14.4%) of 278 grade 2B defects, 54 (55.1%) of 98 grade 3A defects, and three
      (33.3%) of nine grade 3B defects. Subchondral bone marrow edema was also seen
      beneath four (1.4%) of 238 articular surfaces that appeared normal at
      arthroscopy. The mean depth and cross-sectional area of subchondral bone marrow
      edema increased with increasing grade of the articular cartilage lesion.
      CONCLUSION: Higher grades of articular cartilage defects are associated with
      higher prevalence and greater depth and cross-sectional area of subchondral bone
      marrow edema.

PMID- 16424244
TI  - Multipolar radiofrequency ablation with internally cooled electrodes:
      experimental study in ex vivo bovine liver with mathematic modeling.
AB  - PURPOSE: To evaluate the size and geometry of thermally induced coagulation by
      using multipolar radiofrequency (RF) ablation and to determine a mathematic model
      to predict coagulation volume. MATERIALS AND METHODS: Multipolar RF ablations (n
      = 80) were performed in ex vivo bovine livers by using three internally cooled
      bipolar applicators with two electrodes on the same shaft. Applicators were
      placed in a triangular array (spacing, 2-5 cm) and were activated in multipolar
      mode (power output, 75-225 W). The size and geometry of the coagulation zone,
      together with ablation time, were assessed. Mathematic functions were fitted, and
      the goodness of fit was assessed by using r(2). RESULTS: Coagulation volume,
      short-axis diameter, and ablation time were dependent on power output and
      applicator distance. The maximum zone of coagulation (volume, 324 cm(3); short
      axis diameter, 8.4 cm; ablation time, 193 min) was induced with a power output of
      75 W at an applicator distance of 5 cm. Coagulation volume and ablation time
      decreased as power output increased. Power outputs of 100-125 W at applicator
      distances of 2-4 cm led to a reasonable compromise between coagulation volume and
      ablation time. At 2 cm (100 W), coagulation volume, short-axis diameter, and
      ablation time were 66 cm(3), 4.5 cm, and 19 min, respectively; at 3 cm (100 W),
      90 cm(3), 5.2 cm, and 22 min, respectively; at 4 cm (100 W), 132 cm(3), 6.1 cm,
      and 27 min, respectively; at 2 cm (125 W), 56 cm(3), 4.2 cm, and 9 min,
      respectively; at 3 cm (125 W), 73 cm(3), 4.9 cm, and 12 min, respectively; and at
      4 cm (125 W), 103 cm(3), 5.5 cm, and 16 min, respectively. At applicator
      distances of 4 cm (>125 W) and 5 cm (>100 W), the zones of coagulation were not
      confluent. Coagulation volume (r(2) = 0.80) and RF ablation time (r(2) = 0.93)
      were determined by using the mathematic model. CONCLUSION: Multipolar RF ablation
      with three bipolar applicators may produce large volumes of confluent coagulation
      ex vivo. A compromise is necessary between prolonged RF ablations at lower power
      outputs, which produce larger volumes of coagulation, and faster RF ablations at
      higher power outputs, which produce smaller volumes of coagulation.

PMID- 16424245
TI  - Abdominal and iliac arterial stenoses: comparative double-blinded randomized
      study of diagnostic accuracy of 3D MR angiography with gadodiamide or
      gadopentetate dimeglumine.
AB  - PURPOSE: To prospectively evaluate accuracy of gadolinium-enhanced three
      dimensional (3D) magnetic resonance (MR) angiography with gadodiamide and
      gadopentetate dimeglumine (0.1 mmol/kg), with intraarterial DSA as reference
      standard, for imaging abdominal and iliac arterial stenoses. MATERIALS AND
      METHODS: The study was approved by all institutional review boards; informed
      consent was obtained from each subject before procedures. Two hundred forty-seven
      subjects were included; 240 received either contrast agent and were available for
      safety analysis; 222 were available for accuracy analysis. Enhanced 3D MR
      angiography and DSA were performed; image data were evaluated in a double-blinded
      randomized study. Stenoses were classified as not relevant (<50% stenosis) or
      relevant (> or =50%). For detection of main stenosis, accuracy with enhanced 3D
      MR angiography compared with that with DSA was determined. RESULTS: The
      difference in accuracy for imaging with gadodiamide and gadopentetate was 3.6%.
      Noninferiority was inferred because the lower bound of the exact two-sided 95%
      confidence interval was -10.1 and was above the noninferiority margin (-15%).
      Accuracy for detection of the main stenosis was low, 56.4% for gadodiamide and
      52.8% for gadopentetate group. Subgroup analysis with exclusion of inferior
      mesenteric artery and internal iliac arteries and the most false-positive
      stenosis classifications yielded better results: 76.6% and 71.6%, respectively.
      Sensitivity, specificity, and negative and positive predictive values did not
      differ substantially between study groups. In the main analysis, values were 44%,
      96%, 35%, and 97% for gadodiamide and 44%, 83%, 30%, and 90% for gadopentetate,
      respectively. In the subgroup analysis, values were 66%, 95%, 61%, and 96% for
      gadodiamide and 63%, 86%, 58%, and 88% for gadopentetate, respectively.
      CONCLUSION: Noninferiority of gadodiamide versus gadopentetate was verified based
      on the primary end point, which was accuracy for detection of the main stenosis
      with enhanced 3D MR angiography compared with DSA.

PMID- 16424246
TI  - Myocardial tissue phase mapping with cine phase-contrast mr imaging: regional
      wall motion analysis in healthy volunteers.
AB  - PURPOSE: To establish prospectively a database of normal three-dimensional
      systolic and diastolic endocardial and epicardial velocity values for all
      myocardial segments in healthy volunteers by using cine phase-contrast velocity
      magnetic resonance imaging, also called tissue phase mapping (TPM). MATERIALS AND
      METHODS: The study was approved by the institutional ethics committee and was
      conducted according to principles of the Declaration of Helsinki; each subject
      provided informed written consent. Ninety-six healthy volunteers (57 [59%] men,
      39 [41%] women; mean age, 38 years +/- 12 [standard deviation]) underwent cardiac
      phase-contrast imaging with a black blood segmented k-space gradient-echo
      sequence for the analysis of three-dimensional myocardial velocity with high
      spatial resolution at 1.5 T on basal, midventricular, and apical short-axis
      views. Eighteen consecutive volunteers were imaged twice to determine interstudy
      reproducibility, and intra- and interobserver variability values were analyzed.
      Systolic and diastolic velocity curves were analyzed for peak velocity and time
      to peak velocity in the radial, circumferential, and longitudinal directions, as
      well as for torsion rate and longitudinal strain rate. Mixed-effects models with
      a random intercept for volunteers were used to test differences among the three
      ventricular sections and the transmural, endocardial, and epicardial parameters.
      RESULTS: TPM enabled reproducible assessment of myocardial velocity with small
      intra- and interobserver variability values. Systolic peak radial velocity was
      lowest at the apical level (P < .001); diastolic peak radial velocity was similar
      at all three myocardial levels (P = .73). As viewed from the apex, a relative
      counterclockwise rotation during systole was followed by a relative clockwise
      rotation of the apex against the base. Diastolic and systolic peak longitudinal
      velocity values decreased from base to apex (P < .001). A gradient between
      endocardium and epicardium was observed for radial velocity values, with greater
      endocardial velocity values (P < .001). CONCLUSION: TPM is a reproducible
      comprehensive modality for assessment of regional wall motion, and intra- and
      interobserver variability values are low.

PMID- 16424247
TI  - Association between extrinsic and intrinsic carpal ligament injuries at MR
      arthrography and carpal instability at radiography: initial observations.
AB  - PURPOSE: To retrospectively compare the presence or absence of carpal instability
      on radiographs with the findings of magnetic resonance (MR) arthrographic
      evaluation of intrinsic and extrinsic ligament tears in patients with chronic
      wrist pain. MATERIALS AND METHODS: The institutional review board approved this
      study and did not require informed consent. Signs of carpal instability were
      assessed on static and dynamic radiographs of the wrist obtained in 72 patients
      (24 female, 48 male; mean age, 36 years; age range, 14-59 years) with
      posttraumatic wrist pain. MR arthrography was subsequently performed. Two
      musculoskeletal radiologists independently analyzed the radiographs and MR
      images. Each intrinsic and extrinsic ligament was individually evaluated for the
      presence of a ligament tear. The extent of the tear also was recorded.
      Interobserver agreement regarding MR arthrographic findings was tested by
      calculating kappa statistics. Statistical comparison between radiography and MR
      arthrography was performed by using the Fisher exact test. RESULTS: Twenty-five
      triangular fibrocartilage complex, 18 (five partial, 13 complete) scapholunate
      ligament, and 25 (10 partial, 15 complete) lunotriquetral ligament tears were
      visualized. Twenty-two (all complete) extrinsic ligament tears were detected: two
      radial collateral ligament, 10 radioscaphocapitate ligament, and 10
      radiolunotriquetral ligament tears. Interobserver agreement regarding intrinsic
      and extrinsic ligament tear detection at MR arthrography was excellent (kappa =
      0.80). Nineteen patients had evidence of carpal instability on radiographs.
      Fourteen (52%) of 27 patients with at least one complete intrinsic lesion had no
      sign of carpal instability. On the other hand, the association of scapholunate
      ligament and/or lunotriquetral ligament and extrinsic ligament tears was
      significantly correlated (P < .001) with carpal instability at radiography.
      CONCLUSION: The presence or absence of carpal instability on radiographs depends
      on the association between intrinsic and extrinsic ligament tears-even partial
      ones-rather than on the presence of intrinsic ligament tears alone, even when the
      tears are complete.

PMID- 16424248
TI  - Asymptomatic central venous stenosis in hemodialysis patients.
AB  - PURPOSE: To retrospectively evaluate the natural history of high-grade (>50%)
      asymptomatic central venous stenosis (CVS) in hemodialysis patients and the
      outcome of serial treatment of CVS with percutaneous transluminal angioplasty
      (PTA). MATERIALS AND METHODS: The institutional review board granted exemption
      for this retrospective study, the need for informed consent was waived, and all
      data collection was in compliance with HIPAA. Patients with hemodialysis access
      requiring maintenance procedures between 1998 and 2004 and incidentally found to
      have ipsilateral (> or =50%) CVS were identified from a departmental database.
      Thirty-five patients (19 men, 16 women; mean age, 58.7 years) with 38 grafts met
      inclusion criteria, and 86 venograms were reviewed. CVS was measured by using
      venograms obtained before and after PTA, if performed. Patients with arm
      swelling, multiple CVS, indwelling catheters, and stents at the first encounter
      were excluded. CVS progression was calculated by dividing the change in the
      degree of stenosis by the time between venographic examinations. Wilcoxon rank
      sum test was used to evaluate differences in rate of CVS progression between
      treated and nontreated patients. RESULTS: Mean degree of CVS before intervention
      was 71% (range, 50%-100%). Sixty-two percent (53 of 86) of lesions had associated
      collateral vessels; 28% (24 of 86) of CVSs were not treated. Mean degree of
      stenosis in this group was 72% (range, 30%-100%); mean progression was -0.08
      percentage point per day. No untreated CVS progressed to symptoms, stent
      placement, or additional CVS. Seventy-two percent (62 of 86) of CVSs were treated
      with PTA. Mean degree of stenosis in this group was 74% (range, 50%-100%) before
      and 40% (range, 0%-75%) after treatment; mean progression was 0.21 percentage
      point per day after treatment (P = .03). Six (8%) of 62 treatments were followed
      by CVS escalation; one patient developed arm swelling, four required stents, and
      four developed additional CVS. CONCLUSION: PTA of asymptomatic CVS greater than
      50% in the setting of hemodialysis access maintenance procedures was associated
      with more rapid stenosis progression and escalation of lesions, compared with a
      nontreatment approach.

PMID- 16424249
TI  - Three-dimensional US of the fetus: volume imaging.
AB  - PURPOSE: To retrospectively compare the rapidity, efficiency, and accuracy of
      three-dimensional (3D) and two-dimensional (2D) ultrasonography (US) for complete
      anatomic survey in fetuses at 17-21 weeks of gestation. MATERIALS AND METHODS:
      Institutional review board approval was obtained, informed consent was waived,
      and the study was HIPAA compliant. Fifty consecutive women undergoing fetal
      anatomic survey at 17-21 weeks of gestation formed the study cohort. After
      standard 2D US was performed by one of eight sonographers, the same sonographer
      also obtained five 3D volumes to encompass the entire fetal anatomy. Three
      physicians interpreting the scans independently evaluated the completeness of the
      examination and time needed to read the scans, comparing the standard 2D method
      with the 3D volume reconstruction technique. The paired t test was used to
      compare biparietal diameter (BPD), femur length, and performance times between
      the 3D measurements and the 2D measurement. The t test was used to compare fetal
      anatomy according to volume angle. Differences were significant when P < .05.
      RESULTS: Mean time to perform 2D US was 19.6 minutes per examination, whereas
      mean time to perform complete 3D volume acquisition was 1.8 minutes. Mean times
      needed to interpret 3D images and measure the BPD and femur were 5.53, 4.79, and
      5.34 minutes for the three interpreting physicians. Compared with complete fetal
      surveys performed with 2D US, individual fetal anatomic landmarks (except for
      fetal arms and cavum septum pellucidum) were identified more than 94% of the time
      by using 3D US. Grouping anatomic views by region, the heart, head, extremities,
      and abdominal views were completely seen in 88%, 90%, 90%, and 95% of patients,
      respectively. No significant difference was seen between the three physicians
      regarding completeness of the 3D examinations (P = .7). One fetus had multiple
      anomalies, with 3D volumes identified as abnormal by all three physicians.
      Overall, 74% of 3D BPD measurements were within 1 mm of the 2D measurements, and
      64% of 3D femur measurements were within 1 mm of the 2D measurements. CONCLUSION:
      The standard fetal anatomic survey can be performed in less than 2 minutes with
      3D volume US, and the volumes can be interpreted in 6-7 minutes, compared with a
      mean of 19.6 minutes to perform standard 2D US.

PMID- 16424250
TI  - Endorectal MR imaging in the evaluation of seminal vesicle invasion: diagnostic
      accuracy and multivariate feature analysis.
AB  - PURPOSE: To retrospectively determine the accuracy of endorectal magnetic
      resonance (MR) imaging in demonstrating seminal vesicle invasion (SVI) and to
      investigate the MR imaging features that can predict SVI. MATERIALS AND METHODS:
      The Institutional Review Board granted exempt status for this retrospective
      study, with waiver of informed consent; patient data were collected and handled
      in accordance with HIPAA regulations. Fifty-one men (age range, 44-73 years) with
      SVI and 303 men (age range, 40-76 years) without SVI who underwent endorectal MR
      imaging before radical prostatectomy between January 2000 and October 2004 were
      included in the study. Endorectal MR images were retrospectively and
      independently analyzed by two radiologists for SVI, tumor at prostate base,
      extracapsular extension, and other features considered indicative of SVI. Areas
      under the receiver operating characteristic curves (AUCs) were used to assess the
      accuracy of detecting SVI at endorectal MR imaging. A multiple logistic
      regression was used to explore the combinations of MR imaging features that might
      facilitate the detection of SVI. RESULTS: Readers 1 and 2 had an AUC of 0.93 and
      0.81, respectively, for the detection of SVI. For both readers, the features that
      had the highest sensitivity and specificity were low signal intensity within the
      seminal vesicle and lack of preservation of seminal vesicle architecture. At
      multiple regression analysis, tumor at the prostate base that extended beyond the
      capsule and low signal intensity within a seminal vesicle that has lost its
      normal architecture were highly predictive of SVI. CONCLUSION: Endorectal MR
      imaging is accurate in demonstrating SVI prior to radical prostatectomy, and
      recognition of the most predictive features may facilitate the use of this
      modality.

PMID- 16424252
TI  - Evaluation of Duroc- vs. Pietrain-sired pigs for growth and composition.
AB  - Accurate evaluations of growth and composition traits enable better management
      decisions regarding genetic merit, feeding, and marketing. Sires from Duroc and
      Pietrain populations were used to produce crossbred pigs, which were evaluated
      for growth and composition traits. All parents were normal for the ryanodine
      receptor gene. Boars from each breed were mated to either Yorkshire or F1
      Yorkshire-Landrace females with 307 offspring evaluated from birth through 26 wk
      of age. No significant differences between sire breeds were seen for pig BW from
      birth through 10 wk of age. Body weight, 10th rib backfat (BF10), last rib
      backfat (LRF), and loin muscle area (LMA) were serially measured at 10, 13, 16,
      19, 22, 24, and 26 wk of age. At 26 wk of age, Duroc-sired progeny were heavier
      (143.4 vs. 132.7 kg, P < 0.001), had more BF10 (27.1 vs. 23.7 mm, P < 0.001) and
      LRF (21.2 vs. 19.2 mm, P < 0.001), but had similar LMA (46.4 vs. 47.1 cm2)
      compared with Pietrain-sired progeny. Mean feed efficiency did not differ between
      breed of sire in any period of the study. Duroc progeny had a greater ADG (980.1
      vs. 892.3 g/d, P < 0.001) from 10 to 26 wk of age than Pietrain-sired pigs.
      Composition traits of fat-free total lean (FFTOLN), total fat tissue (TOFAT),
      empty body protein (EBPRO), and empty body lipid (EBLIPID) were calculated.
      Random regression animal models with polynomial regression on week on-test were
      fitted to BW, BF10, LRF, LMA, FFTOLN, TOFAT, EBPRO, and EBLIPID from 10 to 26 wk
      of age. Duroc-sired barrows tended to grow faster but with more fat tissue, and
      Pietrain-sired gilts were slower growing but leaner, whereas Duroc-sired gilts
      and Pietrain-sired barrows were intermediate for growth and backfat measures.
      Serial heritability estimates generally increased from 10 to 26 wk of age with
      ranges as follows: BW (0.05 to 0.39), BF10 (0.13 to 0.76), LRF (0.11 to 0.79),
      LMA (0.05 to 0.73), FFTOLN (0.07 to 0.16), TOFAT (0.19 to 0.45), EBPRO (0.02 to
      0.55), and EBLIPID (0.12 to 0.60). Pigs sired by Duroc and Pietrain boars had
      similar lean tissue growth but achieved it through different mechanisms.

PMID- 16424253
TI  - Comparison of feed energy costs of maintenance, lean deposition, and fat
      deposition in three lines of mice selected for heat loss.
AB  - Three replications of mouse selection populations for high heat loss (MH), low
      heat loss (ML), and a nonselected control (MC) were used to estimate the feed
      energy costs of maintenance and gain and to test whether selection had changed
      these costs. At 21 and 49 d of age, mice were weighed and subjected to dual x-ray
      densitometry measurement for prediction of body composition. At 21 d, mice were
      randomly assigned to an ad libitum, an 80% of ad libitum, or a 60% of ad libitum
      feeding group for 28-d collection of individual feed intake. Data were analyzed
      using 3 approaches. The first approach was an attempt to partition energy intake
      between costs for maintenance, fat deposition, and lean deposition for each
      replicate, sex, and line by multiple regression of feed intake on the sum of
      daily metabolic weight (kg(0.75)), fat gain, and lean gain. Approach II was a
      less restrictive attempt to partition energy intake between costs for maintenance
      and total gain for each replicate, sex, and line by multiple regression of feed
      intake on the sum of daily metabolic weight and total gain. Approach III used
      multiple regression on the entire data set with pooled regressions on fat and
      lean gains, and subclass regressions for maintenance. Contrasts were conducted to
      test the effect of selection (MH - ML) and asymmetry of selection [(MH + ML)/2 -
      MC] for the various energy costs. In approach I, there were no differences
      between lines for costs of maintenance, fat deposition, or protein deposition,
      but we question our ability to estimate these accurately. In approach II,
      selection changed both cost of maintenance (P = 0.03) and gain (P = 0.05); MH
      mice had greater per unit costs than ML mice for both. Asymmetry of the selection
      response was found in approach II for the cost of maintenance (P = 0.06). In
      approach III, the effect of selection (P < 0.01) contributed to differences in
      the maintenance cost, but asymmetry of selection (P > 0.17) was not evident. Sex
      effects were found for the cost of fat deposition (P = 0.02) in approach I and
      the cost of gain (P = 0.001) in approach II; females had a greater cost per unit
      than males. When costs per unit of fat and per unit of lean gain were assumed to
      be the same for both sexes (approach III), females had a somewhat greater
      estimate for maintenance cost (P = 0.10). We conclude that selection for heat
      loss has changed the costs for maintenance per unit size but probably not the
      costs for gain.

PMID- 16424251
TI  - Identification of a new leucine haplotype (ALQ) at codon 154 in the ovine prion
      protein gene in Spanish sheep.
AB  - Genetic susceptibility to scrapie is closely linked to variations at codons 136,
      154, and 171 of the prion protein (PRNP) gene. This association between the PRNP
      genotype and susceptibility to scrapie is the basis of breeding programs for
      scrapie resistance in different countries. In this paper, we describe the method
      used with 2 Spanish dairy sheep breeds (Churra and Castellana) to ascertain the
      initial status of protection against scrapie as a first step toward adapting
      their breeding schemes to include resistance as a complementary selection
      criterion. The procedure for genotype identification is based on multiplex
      minisequencing methodology and has been shown to be accurate, easy to interpret,
      and to have a medium throughput. The frequency of the ARQ allele was similar in
      the 2 populations at nearly 70%. The ARR allele, associated with resistance in
      the homozygous state, reaches around 23% in Churras and nearly 20% in
      Castellanas. The high-risk VRQ allele appeared at a relatively low frequency in
      both breeds. No other haplotypes were found in these 2 breeds. Furthermore, in
      this screening we found a new allele carrying leucine at codon 154. This new
      genetic variant might play a role in susceptibility to scrapie because codon 154
      belongs to a region considered to have an important role in conformational
      conversion of the cellular to the pathogenic protein.

PMID- 16424254
TI  - Genetic parameter estimates for scrotal circumference and semen characteristics
      of Line 1 Hereford bulls.
AB  - The objectives of this study were to estimate heritability for scrotal
      circumference (SC) and semen traits and their genetic correlations (rg) with
      birth weight (BRW). Semen traits were recorded for Line 1 Hereford bulls (n =
      841), born in 1963 or from 1967 to 2000, that were selected for use at Fort Keogh
      (Miles City, MT) or for sale. Semen was collected by electroejaculation when
      bulls were a mean age of 446 d. Phenotypes were BRW, SC, ejaculate volume,
      subjective scores for ejaculate color, swirl, sperm concentration and motility,
      and percentages of sperm classified as normal and live or having abnormal heads,
      abnormal midpieces, proximal cytoplasmic droplets (primary abnormalities), bent
      tails, coiled tails, or distal cytoplasmic droplets (secondary abnormalities).
      Percentages of primary and secondary also were calculated. Data were analyzed
      using multiple-trait derivative-free REML. Models included fixed effects for
      contemporary group, age of dam, age of bull, inbreeding of the bull and his dam,
      and random animal and residual effects. Random maternal and permanent maternal
      environmental effects were also included in the model for BRW. Estimates of
      heritability for BRW, SC, semen color, volume, concentration, swirl, motility,
      and percentages of normal, live, abnormal heads, abnormal midpieces, proximal
      cytoplasmic droplets, bent tails, coiled tails, distal cytoplasmic droplets, and
      primary and secondary abnormalities were 0.34, 0.57, 0.15, 0.09, 0.16, 0.21,
      0.22, 0.35, 0.22, 0.00 0.16, 0.37, 0.00 0.34 0.00, 0.30, and 0.33, respectively.
      Estimates of rg for SC with color, volume, concentration, swirl, motility, and
      percentages of live, normal, and primary and secondary abnormalities were 0.73,
      0.20, 0.77, 0.40, 0.34, 0.63, 0.33, -0.36, and -0.45, respectively. Estimates of
      rg for BRW with SC, color, volume, concentration, swirl, motility, and
      percentages live, normal, and primary and secondary abnormalities were 0.28,
      0.60, 0.08, 0.58, 0.44, 0.21, 0.34, 0.20, -0.02, and -0.16, respectively. If
      selection pressure was applied to increase SC, all of the phenotypes evaluated
      would be expected to improve. Predicted correlated responses in semen
      characteristics per genetic SD of selection applied to SC were 0.87 genetic SD or
      less. If selection pressure was applied to reduce BRW, the correlated responses
      would generally be smaller but antagonistic to improving all of the phenotypes
      evaluated. Predicted correlated responses in SC and semen characteristics per
      genetic SD of selection applied to BRW were less than 0.35 genetic SD.

PMID- 16424255
TI  - Association of a single nucleotide polymorphism in the calpastatin gene with
      carcass and meat quality traits of beef cattle.
AB  - Calpastatin (CAST) is a naturally occurring protein that inhibits the normal
      tenderization of meat as it ages postmortem. A SNP was identified in the CAST
      gene (a G to C substitution) and genotyped on crossbred commercially fed heifers
      (n = 163), steers (n = 226), and bulls (n = 61) from beef feedlots, and steers (n
      = 178) from a University of Guelph feeding trial. The association of the CAST SNP
      with carcass and meat quality traits was studied. Carcass traits included fat,
      lean, and bone yield; grade fat; LM area; and HCW. Meat quality traits included
      marbling grade; i.m. fat content of LM; tenderness evaluation of LM (Warner
      Bratzler shear force) at 2, 7, 14, and 21 d of postmortem aging; and tenderness
      evaluation of semitendinosus muscle at 7 d of postmortem aging. The mixed model
      used in the analyses included fixed effects of CAST genotype, sex, slaughter
      group, and breed composition (linear covariate); sire was a random effect. For
      the analysis of shear force, i.m. fat content of LM was also included in the
      model as a linear covariate. Shear force measures were analyzed within days of
      postmortem aging and by repeated measures analysis. The CAST SNP allele C was
      more frequent (63%) in the crossbred population than allele G. The CAST SNP was
      associated with shear force across days of postmortem aging (P = 0.005); genotype
      CC yielded beef that was more tender than GG (-0.32 kg +/- 0.13), and CG had
      intermediate tenderness. The corresponding average allele substitution effect (G
      to C substitution) was also highly significant (-0.15 +/- 0.05 kg, P = 0.002). A
      lower percentage of unacceptably tough steaks (shear force > 5.7 kg) at 2 and 7 d
      postmortem was associated with an increasing number of C alleles (P < or = 0.05).
      At 7 d postmortem, the percentage of unacceptably tough steaks decreased by 24
      and 35%, respectively, for animals carrying 1 and 2 copies of the C allele
      relative to animals with no C alleles. However, genotype CC had a greater fat
      yield (+1.44 +/- 0.56%; P = 0.037) than genotype GG, with a corresponding allele
      substitution effect of 0.67 +/- 0.27% (P = 0.015). Therefore, the CAST SNP allele
      C was associated with increased LM tenderness across days of postmortem aging
      and, importantly for the beef industry, had a significant reduction in the
      percentage of steaks rated unacceptably tough by consumers based on an assumed
      threshold level.

PMID- 16424257
TI  - Postweaning growth and carcass traits in crossbred cattle from Hereford, Angus,
      Norwegian Red, Swedish Red and White, Friesian, and Wagyu maternal grandsires.
AB  - The objective of this study was to characterize breeds representing diverse
      biological types for postweaning growth and carcass composition traits in
      terminal crossbred cattle. Postweaning growth and carcass traits were analyzed on
      434 steers and 373 heifers obtained by mating F1 cows to Charolais sires.
      Maternal grandsires represented Hereford, Angus, and MARC III (1/4 Hereford, 1/4
      Angus, 1/4 Pinzgauer, and 1/4 Red Poll) dams to Hereford or Angus (British
      Breeds), Norwegian Red, Swedish Red and White, Wagyu, or Friesian breeds. Breed
      groups were slaughtered serially in each of 2 yr (2002 and 2003). Postweaning
      ADG, slaughter weight, hot carcass weight, dressing percentage, percentage
      Choice, LM area, marbling score, USDA yield grade, fat thickness, retail product
      yield (percentage), retail product weight, fat yield (percentage), fat weight,
      bone yield (percentage), and bone weight were analyzed. Maternal grandsire breed
      was significant (P < 0.05) for all traits except dressing percentage, percentage
      Choice, and LM area. Marbling score for animals with Norwegian Red, Wagyu,
      Swedish Red and White, British Breeds, and Friesian inheritance was 550, 544,
      532, 530, and 515, respectively (SEM = 8). Retail product weight for these
      animals was 224, 211, 227, 223, and 223 kg, respectively (SEM = 2 kg). Maternal
      granddam breed was not significant for any of the traits analyzed. Grandsire
      breed effects can be optimized by selection and use of appropriate crossbreeding
      systems.

PMID- 16424256
TI  - Correlated responses in maternal performance following divergent selection for
      heat loss in mice.
AB  - Divergent selection in mice was applied in 3 independent replicates for high
      (maintenance high; MH) and low (maintenance low; ML) heat loss for 16
      generations. An unselected control (maintenance control; MC) was also maintained
      in all replicates. Selection ceased for 26 generations; heat-loss measurement and
      selection resumed at generation 42. Lactation performance, dam weight, dam feed
      intake, and efficiency of production of pup weight were recorded or calculated
      for MH and ML dams in all 3 replicates at generation 46 or 47 with the objective
      of determining whether selection for heat loss has created correlated responses
      in maternal performance. One-half of the dams reared their own litters, and one
      half reared cross-fostered (across lines) litters. Between 10 and 12 litters were
      used from each replicate-line-rearing class. Litter size was recorded, and
      litters were standardized to 8 pups within 24 h of birth. For cross fostering, MH
      litters were matched to ML litters born within 24 h of each other, and MH-ML
      litter pairs were cross-fostered at 3 d of age. A weigh-suckle-weigh protocol was
      used to obtain milk production estimates over a 2-h suckling period at 6, 9, 12,
      and 15 d. Dam (plus litter) feed intake was also recorded at these times and was
      calculated as the disappearance of feed over 3-d intervals. Dams of the MH
      selection tended (P < 0.11) to have greater litter size than those of the ML
      selection; litter size of MC dams was intermediate. Line of dam affected milk
      production (P = 0.04) and dam feed intake (P < 0.03) as MH dams produced more
      milk and consumed more feed than ML dams. Average milk production for the 2-h
      measurement period was 1.70 +/- 0.07 and 1.41 +/- 0.07 g, and average 3-d feed
      consumption was 50.8 +/- 1.2 and 45.2 +/- 1.2 g for MH and ML dams, respectively.
      Cross-fostering had no effect (P > 0.86) on milk production. Line of dam tended
      to affect 21-d litter weight (P = 0.15) with litters reared by MH dams weighing
      more than those reared by ML dams, but there was no difference (P > 0.86) in 21-d
      dam weights. Efficiency of producing litter weight (litter 15-d weight: dam plus
      litter feed intake from d 6 to 15) was greater (0.49 vs. 0.46, SE = 0.009; P =
      0.03) for ML than for MH dams. Selection for reduced heat loss (lower maintenance
      feed intake in the ML line) resulted in reduced milk production and feed intake
      in dams and greater efficiency of litter weight production.

PMID- 16424258
TI  - Evaluation of the ovine callipyge locus: IV. Genotypic effects on reproductive
      traits.
AB  - A resource population of ewes derived from Dorset and Romanov grandparents was
      generated over 5 yr to provide genotypic and phenotypic data to estimate effects
      of each callipyge genotype on component traits of reproduction. Effects on
      ovulation rate were estimated from data recorded by examination of ovaries from
      serially slaughtered ewe lambs (n = 174) born in 1994 and 1995. Productivity and
      longevity through 5 yr of age were recorded on a total of 265 F2 ewes produced in
      1996 through 1998. Number of lambs born, birth weights, and weaning weights of
      lambs were calculated for each ewe. Weaning weight was recorded for each lamb and
      adjusted for age to 56 and 32 d for dam- and nursery-reared lambs, respectively.
      Longevity was determined as a binary trait based on the presence or absence of
      the ewe in the breeding flock at 5 yr of age. Ewes generated 937 records for
      breeding weight and 925 records for conception rate, which was determined on ewes
      exposed and still present at the start of each lambing season. Seven hundred
      seventeen records were analyzed for traits based on the number of ewes lambing.
      Genotypes for the causative callipyge mutation were determined using a matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry assay. Each
      ewe was classified into 1 of 4 genotypes; NMatNPat, NMatCPat, CMatNPat, or
      CMatCPat, where N represents wild type and C represents the mutant allele. The
      mean ovulation rate of the ewe lambs genotyped NMatNPat was greater (P < 0.02)
      than that exhibited by NMatCPat; however, the estimated difference of 0.25 ovum
      in the ewe lambs did not affect the number born. The live weight of NMatCPat ewes
      at breeding was 2.5 kg less than that of other genotypes (P < 0.01). The
      callipyge genotype class did not significantly affect conception rates,
      fecundity, maternal ability, or ewe longevity. Maintaining a ewe flock to produce
      homozygous mutant rams for use in terminal sire mating systems presents no
      unusual problems from a reproduction standpoint.

PMID- 16424259
TI  - Comparison of genetic gains per year for carcass traits among breeding programs
      in the Japanese Brown and the Japanese Black cattle.
AB  - The breeding program for beef cattle in Japan has changed dramatically over 4
      decades. Visual judging was done initially, but progeny testing in test stations
      began in 1968. In the 1980s, the genetic evaluation program using field records,
      so-called on-farm progeny testing, was first adopted in Oita, Hyogo, and Kumamoto
      prefectures. In this study, genetic trends for carcass traits in these 3 Wagyu
      populations were estimated, and genetic gains per year were compared among the 3
      different beef cattle breeding programs. The field carcass records used were
      collected between 1988 and 2003. The traits analyzed were carcass weight, LM
      area, rib thickness, s.c. fat thickness, and beef marbling standard number. The
      average breeding values of reproducing dams born the same year were used to
      estimate the genetic trends for the carcass traits. For comparison of the 3
      breeding programs, birth years of the dams were divided into 3 periods reflecting
      each program. Positive genetic trends for beef marbling standard number were
      clearly shown in all populations. The genetic gains per year for all carcass
      traits were significantly enhanced by adopting the on-farm progeny testing
      program. These results indicate that the on-farm progeny testing program with
      BLUP is a very powerful approach for genetic improvement of carcass traits in
      Japanese Wagyu beef cattle.

PMID- 16424260
TI  - Growth hormone and ghrelin receptor genes are differentially expressed between
      genetically lean and fat selection lines of sheep.
AB  - The objective of this study was to determine whether differences in mRNA levels
      of key pituitary genes that regulate GH production, pituitary development, and
      growth were present and/or associated with divergent body composition phenotypes
      observed between sheep from genetically divergent lean and fat selection lines.
      Real-time PCR transcription profiles for pituitary specific transcription factor
      1, prophet of pit1, GH, GH receptor, GH secretagogue receptor, GHRH receptor,
      leptin receptor, and somatostatin receptors 1 and 2 were determined in pituitary
      tissue. There was a difference in the amount of both GH (P < 0.001) and GH
      secretagogue receptor (P < 0.001) mRNA between the selection lines (5 females and
      5 males per line; 20 wk of age); the lean line had greater abundance than the fat
      line, irrespective of which endogenous control gene was used. The results
      obtained for GHRH receptor were equivocal but suggestive; there were greater GHRH
      receptor mRNA levels (P < 0.001) in the lean line using beta-2-microglobulin as
      the endogenous control but not when hypoxanthine phosphoribosyltransferase and
      glyceraldehyde-3-phosphate dehydrogenase were used. No difference in pituitary
      specific transcription factor 1, prophet of pit1, GH receptor, leptin receptor,
      or somatostatin receptors 1 and 2 mRNA concentration was observed between the
      lines. The greater abundance of GH mRNA in the pituitary somatotropes from
      genetically lean animals appears to be associated with increased levels of GH
      secretagogue receptor mRNA and possibly GHRH receptor mRNA. This suggests that
      the difference in GH secretion between the lines may be due to differences in the
      afferent signals, such as ghrelin and/or GHRH, arising from the hypothalamus, or
      as a result of differential pituitary sensitivity to these hormones.

PMID- 16424261
TI  - Synchronization of estrus in suckled beef cows for detected estrus and artificial
      insemination and timed artificial insemination using gonadotropin-releasing
      hormone, prostaglandin F2alpha, and progesterone.
AB  - We determined whether a fixed-time AI (TAI) protocol could yield pregnancy rates
      similar to a protocol requiring detection of estrus, or estrous detection plus
      TAI, and whether adding a controlled internal device release (CIDR) to GnRH-based
      protocols would enhance fertility. Estrus was synchronized in 2,598 suckled beef
      cows at 14 locations, and AI was preceded by 1 of 5 treatments: 1) a CIDR for 7 d
      with 25 mg of PG F(2alpha) (PGF) at CIDR removal, followed by detection of estrus
      and AI during the 84 h after PGF; cows not detected in estrus by 84 h received
      100 mug of GnRH and TAI at 84 h (control; n = 506); 2) GnRH administration,
      followed in 7 d with PGF, followed in 60 h by a second injection of GnRH and TAI
      (CO-Synch; n = 548); 3) CO-Synch plus a CIDR during the 7 d between the first
      injection of GnRH and PGF (CO-Synch + CIDR; n = 539); 4) GnRH administration,
      followed in 7 d with PGF, followed by detection of estrus and AI during the 84 h
      after PGF; cows not detected in estrus by 84 h received GnRH and TAI at 84 h
      (Select Synch & TAI; n = 507); and 5) Select Synch & TAI plus a CIDR during the 7
      d between the first injection of GnRH and PGF (Select Synch + CIDR & TAI; n =
      498). Blood samples were collected (d -17 and -7, relative to PGF) to determine
      estrous cycle status. For the control, Select Synch & TAI, and Select Synch +
      CIDR & TAI treatments, a minimum of twice daily observations for estrus began on
      d 0 and continued for at least 72 h. Inseminations were performed using the AM/PM
      rule. Pregnancy was diagnosed by transrectal ultrasonography. Percentage of cows
      cycling at the initiation of treatments was 66%. Pregnancy rates (proportion of
      cows pregnant to AI of all cows synchronized during the synchronization period)
      among locations across treatments ranged from 37% to 67%. Pregnancy rates were
      greater (P < 0.05) for the Select Synch + CIDR & TAI (58%), CO-Synch + CIDR
      (54%), Select Synch & TAI (53%), or control (53%) treatments than the CO-Synch
      (44%) treatment. Among the 3 protocols in which estrus was detected, conception
      rates (proportion of cows that became pregnant to AI of those exhibiting estrus
      during the synchronization period) were greater (P < 0.05) for Select Synch & TAI
      (70%; 217 of 309) and Select Synch + CIDR & TAI (67%; 230 of 345) cows than for
      control cows (61%; 197 of 325). We conclude that the CO-Synch + CIDR protocol
      yielded similar pregnancy rates to estrous detection protocols and is a reliable
      TAI protocol that eliminates detection of estrus when inseminating beef cows.

PMID- 16424262
TI  - Use of recombinant gonadotropin-releasing hormone antigens for
      immunosterilization of beef heifers.
AB  - The objectives of this study were to evaluate the effects of immunization against
      recombinant GnRH fusion proteins and growth promotants on onset of puberty,
      feedlot performance, and carcass characteristics of beef heifers. Heifers were
      immunized against an ovalbumin fusion protein containing 7 GnRH peptides (oGnRH,
      n = 12), a thioredoxin fusion protein containing 7 GnRH peptides (tGnRH, n = 12),
      a combination of oGnRH plus tGnRH (otGnRH, n = 12), or a combination of ovalbumin
      and thioredoxin (control, n = 11). Each heifer received a primary immunization
      containing 1 mg of protein in 1 mL of adjuvant injected into the mammary gland at
      wk 0 (mean age = 38 wk) and booster immunizations at wk 6 and 12. Six heifers
      within each treatment received Synovex H implants at wk -2. Weekly blood samples
      were collected from wk -2 to 26 for determination of serum progesterone
      concentrations and GnRH antibody titers. In GnRH-immunized heifers, GnRH antibody
      titers increased after the first booster injection, peaked after the second
      booster injection, and remained elevated through the end of the study (P < 0.01).
      Heifers immunized against oGnRH achieved greater (P < 0.05) GnRH antibody titers
      than tGnRH heifers but did not differ (P = 0.20) from otGnRH heifers. During the
      26-wk study, ovulation was prevented (P < 0.05) in 10 out of 12, 12 out of 12, 11
      out of 12, and 0 out of 11 tGnRH, oGnRH, otGnRH, and control heifers,
      respectively. At slaughter, uterine weights were lighter (P < 0.01) for GnRH
      immunized heifers than control heifers. Synovex H-implanted heifers had greater
      (P < 0.05) ADG from wk -2 to 26, greater LM area, and lesser percentages of KPH,
      yield grade, and quality grade than nonimplanted heifers, regardless of the
      immunization treatment. Immunization against GnRH fusion proteins resulted in
      production of antibodies against GnRH that prevented ovulation in 92% of the
      heifers without affecting feedlot or carcass performance. Implanting heifers with
      Synovex H improved ADG, LM area, and yield grade. Improvements in delivery of the
      oGnRH vaccine may provide a feasible alternative to surgical spaying of heifers.

PMID- 16424263
TI  - Effect of carprofen administration during banding or burdizzo castration of bulls
      on plasma cortisol, in vitro interferon-gamma production, acute-phase proteins,
      feed intake, and growth.
AB  - The objective of this study was to determine the effect of carprofen (C)
      administration before banding or burdizzo castration of bulls on cortisol, in
      vitro interferon-gamma (IFN-gamma) production, acute-phase proteins, feed intake,
      and growth. Fifty Holstein Friesian bulls (5.5 mo old; 191 +/- 3.7 kg) were
      blocked by weight and assigned randomly to 1 of 5 treatments (n = 10/treatment):
      1) untreated control (2) banding castration at 0 min (Band); 3) Band following an
      i.v. injection of 1.4 mg/kg of BW of C at -20 min (Band+C); 4) Burdizzo
      castration at 0 min (Burd); or 5) Burd following 1.4 mg/kg of BW of C at -20 min
      (Burd+C). Castration acutely increased plasma cortisol concentrations compared
      with control; no significant differences occurred in peak and interval to peak
      cortisol responses between Band and Band+C or Burd and Burd+C groups. The
      administration of C in Band+C reduced (P < 0.05) the cortisol concentration
      between 6 and 12 h postcastration compared with Band animals. Overall, the
      integrated cortisol response was greater (P < 0.05) in the castrates than in
      control, whereas C treatments tended to reduce this response compared with Band
      (P = 0.08) and Burd (P = 0.07), respectively. Plasma fibrinogen was elevated in
      Band animals on d 14 and in Burd animals on d 3 and 14. Carprofen administration
      reduced Band- and Burd-induced fibrinogen production on d 14 and 3, respectively.
      Plasma haptoglobin was elevated in Band animals on d 3 and 35 compared with
      control, and C administration was effective in reducing the haptoglobin elevation
      on d 35 in Band+C compared with Band. There were no differences among treatments
      in in vitro IFN-gamma production induced by concanavalin A and phytohemagglutinin
      on d 1 and 2. Overall from d -1 to 16, there were no DMI differences among
      treatments. From d -1 to 35, there were no ADG differences among treatments. In
      conclusion, banding and burdizzo castration increased plasma cortisol with no
      change in in vitro IFN-gamma production. Carprofen (1.4 mg/kg of BW) tended to
      reduce the integrated cortisol response, and it reduced cortisol secretion in
      banded animals between 6 and 12 h postcastration. There was an increased acute
      phase protein production following castration; this response was effectively
      moderated by the administration of C before castration.

PMID- 16424264
TI  - Effects of breed and season on performance of lactating sows in a tropical humid
      climate.
AB  - A total of 179 lactations obtained on 71 multiparous sows [30 Creole (CR) and 41
      Large White (LW)] between June 2001 and July 2004 were used to determine effects
      of breed (CR vs. LW) and season (hot vs. warm) in a tropical humid climate on
      performance during a 28-d lactation period. Mean daily ambient temperature was
      greater during the hot season than during the warm season (26.0 vs. 23.8 degrees
      C), and relative humidity was similar in both seasons (85% on average). For both
      breeds, ADFI was reduced (-700 g/d, P < 0.01), sow BW loss was greater (17 vs. 12
      kg, P < 0.01), and piglet growth was reduced (197 vs. 210 g/d, P < 0.05) during
      the hot vs. the warm season. At farrowing, LW sows were heavier (255 vs. 186 kg,
      P < 0.01) and had less backfat (21 vs. 40 mm, P < 0.01) than CR sows. The growth
      rate of CR piglets was lower than that of LW piglets (192 vs. 215 g/d, P < 0.01).
      A breed x season interaction was observed (P < 0.05) for ADFI and sow BW loss.
      During the hot season, the reduction of ADFI was more pronounced in LW than in CR
      sows (-910 vs. -470 g/d). Regardless of the season, BW loss of CR sows remained
      constant (14.2 kg), whereas it increased during the hot season for LW sows (10
      kg). The weaning-to-estrus and the weaning-to-conception intervals were not
      affected by breed or season and averaged 4.8 and 6.1 d, respectively. The rectal
      temperature was greater (0.3 degrees C) during the hot season than during the
      warm season and greater in LW than in CR sows (39.1 vs. 38.8 degrees C, P <
      0.10). This study confirms the negative effect of hot season in a tropical humid
      climate on performance of lactating sows and that breed can have a significant
      effect on lactation performance. The results also suggest that CR sows are more
      heat tolerant than LW sows.

PMID- 16424265
TI  - Effect of gluconic acid on piglet growth performance, intestinal microflora, and
      intestinal wall morphology.
AB  - Gluconic acid (GA) derives from the incomplete oxidation of glucose by some
      Gluconobacter strains. When fed to nonruminant animals, GA is only poorly
      absorbed in the small intestine and is primarly fermented to butyric acid in the
      lower gut. This study investigated the effect of GA on in vitro growth response
      and metabolism of swine cecal microflora and on animal growth performance,
      intestinal wall morphology, and intestinal microflora. During a 24-h in vitro
      cecal fermentation, total gas production and maximum rate of gas production were
      increased by GA (linear, P < 0.001). Ammonia in cecal liquor was reduced by GA
      after 4, 8, and 24 h of fermentation (quadratic, P < 0.01). After 24 h of
      fermentation, total short-chain fatty acids, acetic acid, propionic acid, n
      butyric acid, acetic to propionic acid ratio, and acetic + butyric to propionic
      acid ratio were linearly increased by GA (P < 0.001). In the in vivo study, 48
      piglets were divided into 4 groups and housed in individual cages for 6 wk.
      Piglets received a basal diet with a) no addition (control) or with GA addition
      at b) 3,000 ppm, c) 6,000 ppm, or d) 12,000 ppm. After 6 wk, 4 animals per
      treatment were killed, and samples of intestinal content and mucosa were
      collected. Compared with control, GA tended to increase average daily gain (+13
      and +14% for GA at 3,000 and 6,000 ppm, respectively; P of the model = 0.11;
      quadratic, P < 0.05). Daily feed consumption and gain to feed ratio were not
      influenced by GA. Intestinal counts of clostridia, enterobacteriaceae, and lactic
      acid bacteria were not affected by GA. Gluconic acid tended to increase total
      short-chain fatty acids in the jejunum (+174, +87, and +74% for GA at 3,000,
      6,000, and 12,000 ppm, respectively; P of the model = 0.07; quadratic, P = 0.07).
      Morphological evaluation of intestinal mucosa from jejunum, ileum, and cecum did
      not show any significant differences among treatments. This study showed that
      feeding GA influences the composition and activity of the intestinal microflora
      and may improve growth performance of piglets after weaning.

PMID- 16424266
TI  - Evidence of a dietary selection for methionine by the piglet.
AB  - The objective of the current study was to investigate if there is a preference of
      piglets for diets varying in Met content and whether these preferences change
      with time. For this purpose, a feeding trial was carried out over a period of 6
      wk. Piglets (equal numbers of males and females) with an initial BW of 7.2 +/-
      0.1 kg were randomly subdivided into 4 groups of 12 pigs each. Two reference
      groups were fed either 0.19% Met (low-Met group) or 0.26% Met (high-Met group)
      diets. Two other groups had the choice between 2 diets containing 0.19 or 0.23%
      Met (Met-choice 1 group), or 0.19 or 0.26% Met (Met-choice 2 group). Compared
      with the low-Met group (397 g), daily feed intake was increased by 43%, 60%, and
      82% (P < 0.05) in the Met-choice 1, Met-choice 2, and the high-Met group,
      respectively. Piglets on the Met-choice 1 and Met-choice 2 groups, respectively,
      selected 72 and 80% of the higher Met diet. In the first week, piglets on both
      Met-choice groups selected the diets at random, but they increased their
      preference for the diets higher in Met up to 81 and 89%, respectively, in the
      last experimental week. For the total experiment, mean Met contents of total
      diets were 0.22 and 0.25% in the Met-choice 1 and Met-choice 2 groups,
      respectively. Average daily gain of 195 g in the low-Met group was more than
      doubled (P < 0.05) in the high-Met group. Daily gains of 306 and 366 g in the Met
      choice 1 and 2 groups, respectively, were (P < 0.05) improved compared with the
      low-Met group but lower (P < 0.05) than in the high-Met group. Plasma Met
      concentration of 46.3 micromol/mL in the Met-choice 2 group was greater than in
      the low-Met or the Met-choice 1 groups (25.3 and 32.8 micromol/mL, respectively)
      but lower (P < 0.05) compared with the high-Met group (59.6 micromol/mL).
      Conversely, the sum of essential AA showed a greater (P < 0.05) concentration in
      plasma from pigs on the low-Met and Met-choice 1 groups than in plasma from pigs
      on Met-choice 2 group and the high-Met group. In conclusion, the present data
      demonstrate that piglets are able to discriminate among diets of varying Met
      content. When given a choice, they prefer a diet better balanced for Met to a Met
      deficient diet. As a result of the altered feeding pattern, piglets are able to
      partly redress the depressed performance and altered plasma AA pattern resulting
      from the ingestion of the diet more limiting in Met concentration.

PMID- 16424267
TI  - Site and extent of digestion, duodenal flow, and intestinal disappearance of
      total and esterified fatty acids in sheep fed a high-concentrate diet
      supplemented with high-linoleate safflower oil.
AB  - Our objective was to determine duodenal and ileal flows of total and esterified
      fatty acids and to determine ruminal fermentation characteristics and site and
      extent of nutrient digestion in sheep fed an 80% concentrate diet supplemented
      with high-linoleate (77%) safflower oil at 0, 3, 6, and 9% of DM. Oil was infused
      intraruminally along with an isonitrogenous basal diet (fed at 2% of BW) that
      contained bromegrass hay, cracked corn, corn gluten meal, urea, and limestone.
      Four crossbred wethers (BW = 44.3 +/- 15.7 kg) fitted with ruminal, duodenal, and
      ileal cannulas were used in a 4 x 4 Latin square experiment, in which 14 d of
      dietary adaptation were followed by 4 d of duodenal, ileal, and ruminal sampling.
      Fatty acid intake increased (linear, P = 0.004 to 0.001) with increased dietary
      safflower oil. Digestibilities of OM, NDF, and N were not affected (P = 0.09 to
      0.65) by increased dietary safflower oil. For total fatty acids (free plus
      esterified) and esterified fatty acids, duodenal flow of most fatty acids,
      including 18:2c-9,c-12, increased (P = 0.006 to 0.05) with increased dietary oil.
      Within each treatment, duodenal flow of total and esterified 18:2c-9,c-12 was
      similar (P = 0.32), indicating that duodenal flow of this fatty acid occurred
      because most of it remained esterified. Duodenal flow of esterified 18:1t-11
      increased (P = 0.08) with increased dietary safflower oil, indicating that
      reesterification of ruminal fatty acids occurred. Apparent small intestinal
      disappearance of most fatty acids was not affected (P = 0.19 to 0.98) by
      increased dietary safflower oil, but increased (P = 0.05) for 18:2c-9,c-12, which
      ranged from 87.0 to 97.4%, and for 18:2c-9,t-11 (P = 0.03), which ranged from
      37.9% with no added oil to 99.2% with supplemental oil. For esterified fatty
      acids, apparent small intestinal disappearance was from 80% for 18:3c-9,c-12,c-15
      at the greatest level of dietary oil up to 100% for 18:1t-11 and 18:1c-12 with 0%
      oil. We concluded that duodenal flow of 18:2c-9,c-12 was predominately associated
      with the esterified fraction, suggesting that the extent of ruminal lipolysis was
      decreased with increased dietary high-linoleate safflower oil. Furthermore,
      biohydrogenation intermediates observed in the esterified fatty acids indicated
      that some reesterification occurred, and the high level of apparent absorption of
      esterified fatty acids indicated that intestinal lipolysis did not limit overall
      digestion of the fatty acids fed to the sheep.

PMID- 16424268
TI  - Effects of body condition score at parturition and postpartum supplemental fat on
      adipose tissue lipogenic activity of lactating beef cows.
AB  - Three-year-old Angus x Gelbvieh beef cows nutritionally managed to achieve a BCS
      of 4 +/- 0.07 (479.3 +/- 36.3 kg of initial BW) or 6 +/- 0.07 (579.6 +/- 53.1 kg
      of initial BW) at parturition were used in a 2-yr experiment (n = 36/yr) to
      determine the effects of BCS at parturition and postpartum lipid supplementation
      on cow adipose tissue lipogenesis. Beginning 3 d postpartum, cows within each BCS
      were randomly assigned to be fed hay and a low-fat control supplement or
      supplements with either cracked high-linoleate safflower seeds or cracked high
      oleate safflower seeds until d 60 of lactation. Diets were formulated to be
      isonitrogenous and isocaloric, and safflower seed diets provided 5% DMI as fat.
      Adipose tissue biopsies were collected near the tail-head region of cows on d 30
      and 60 of lactation. Dietary treatment did not affect (P > or = 0.43) adipose
      tissue lipogenesis. Body condition score at parturition did not affect acetate
      incorporation into lipid (P = 0.53) or activity of acetyl CoA carboxylase (P =
      0.77) or fatty acid synthase (P = 0.18). Lipoprotein lipase activity and
      palmitate incorporation into triacyl-glycerol tended to be greater (P = 0.06),
      and palmitate esterification into total acylglycerols was greater (P = 0.01) in
      cows with a BCS of 4 at parturition. Mean activity of acetyl-CoA carboxylase (P <
      0.001), lipoprotein lipase (P = 0.01), and rate of palmitate incorporation into
      monoacylglycerol (P = 0.02), diacylglycerol (P = 0.001), triacylglycerol (P =
      0.003), and total acylglycerols (P = 0.002) were greater at d 30 than d 60,
      suggesting a greater proclivity for fatty acid biosynthesis and esterification by
      adipose tissue at d 30 of lactation. Although dietary lipid supplementation did
      not affect adipose tissue lipogenesis, results suggest that cows with a BCS of 4
      at parturition have a greater propensity to deliver exogenously derived fatty
      acids to the adipocyte surface and incorporate preformed fatty acids into
      acylglycerols as stored adipocyte lipid. Additionally, cows in early lactation
      seemed to be able to synthesize and incorporate more fatty acids into stored
      lipid than cows during peak lactation.

PMID- 16424269
TI  - Effects of malate on diet digestibility, microbial protein synthesis, plasma
      metabolites, and performance of growing lambs fed a high-concentrate diet.
AB  - The objective of this study was to evaluate the effects of malate supplementation
      on growth rate, feed efficiency, and diet digestibility in growing lambs. Twenty
      four Merino lambs with a mean BW of 15.3 +/- 0.22 kg were divided into 3
      homogenous groups. Each group was randomly allocated to 1 of 3 malate (16%
      disodium malate:84% calcium malate) levels: 0 (control), 4 (MAL-4), or 8 (MAL-8)
      g/kg of concentrate. Lambs were fed concentrate and barley straw ad libitum for
      35 d. After a 20-d period, diet digestibility was determined, and microbial N
      flow at the duodenum was estimated from the urinary excretion of purine
      derivatives. Blood samples were taken on d 0, 20, and 35. On d 35, lambs were
      slaughtered and ruminal fluid samples were collected. There were no effects (P =
      0.18 to P = 0.95) of malate on concentrate or straw intake, ADG, carcass yield,
      and apparent digestibility of OM, CP, NDF, or ADF. Malate supplementation did not
      influence (P = 0.80) the daily urinary excretion of total purine derivatives, and
      therefore there were no treatment effects (P = 0.77) on estimated microbial N
      flow at the duodenum. No differences (P > 0.05) among treatments were observed
      for plasma concentrations of glucose, cholesterol, triglycerides, urea-N,
      lactate, or VFA, but malate addition increased (P = 0.003) the molar proportion
      of butyrate in ruminal fluid (4.29, 6.14, and 5.45% of total VFA for control, MAL
      4 and MAL-8, respectively). The use of malate as a feed additive under the
      conditions of the current study did not influence diet intake or digestion, and
      consequently did not improve lamb performance.

PMID- 16424270
TI  - Effect of creep feed supplementation and season on intake, microbial protein
      synthesis and efficiency, ruminal fermentation, digestion, and performance in
      nursing calves grazing native range in southeastern North Dakota.
AB  - Nine ruminally and duodenally cannulated (172 +/- 23 kg of initial BW; Exp. 1)
      and 16 intact (153 +/- 28 kg of initial BW; Exp. 2) crossbred nursing steer
      calves were used to evaluate the effects of creep feed supplementation and
      advancing season on intake, digestion, microbial efficiency, ruminal
      fermentation, and performance while grazing native rangeland. Treatments in both
      experiments were no supplement or supplement fed at 0.45% of BW (DM basis) daily.
      Supplement consisted of 55% wheat middlings, 38.67% soyhulls, 5% molasses, and
      1.33% limestone. Three 15-d collection periods occurred in June, July, and
      August. In Exp. 1, ruminal evacuations were performed and masticate samples were
      collected for diet quality analysis on d 1. Duodenal and fecal samples were
      collected from cannulated calves on d 7 to 12 at 0, 4, 8, and 12 h after
      supplementation. Ruminal fluid was drawn on d 9 and used as the inoculate for in
      vitro digestibility. On d 11, ruminal fluid was collected, and the pH was
      recorded at -1, 1, 2, 4, 8, 12, and 24 h postsupplementation. In Exp. 1 and 2,
      milk intake was estimated using weigh-suckle-weigh on d 15. Steers in Exp. 2 were
      fitted with fecal bags on d 6 to 11 to estimate forage intake. In Exp. 1,
      supplementation had no effect (P = 0.22 to 0.99) on grazed diet or milk
      composition. Apparent total tract OM disappearance increased (P = 0.03), and
      apparent total tract N disappearance tended (P = 0.11) to increase in
      supplemented calves. Microbial efficiency was not affected (P = 0.50) by
      supplementation. There were no differences in ruminal pH (P = 0.40) or total VFA
      concentration (P = 0.21) between treatments, whereas ruminal NH3 concentration
      increased (P = 0.03) in supplemented compared with control calves. In Exp. 2,
      supplementation decreased (P = 0.02) forage OM intake (OMI; % of BW) and
      increased (P = 0.06) total OMI (% of BW). Supplementation had no effect on ADG (P
      = 0.94) or G:F (P = 0.35). Supplementation with a wheat middlings and soybean
      hull-based creep feed reduced forage OMI but improved total tract OM and N
      digestion and had minimal effects on ruminal fermentation or performance.
      Supplementation with a wheat middlings and soybean hulls-based creep feed might
      improve OM and N digestion, but might not produce significantly greater BW gains
      compared with no supplementation.

PMID- 16424271
TI  - Influence of steam-flaked corn moisture level and density on the site and extent
      of digestibility and feeding value for finishing cattle.
AB  - Performance and digestibility experiments were conducted to determine the
      influence of moisture and flake density (FD) on the feeding value of steam-flaked
      corn (SFC). Dietary treatments consisted of finishing diets that contained 78%
      (DM basis) SFC that was tempered using 0, 6, or 12% moisture and processed to
      either 360 (SF28) or 310 (SF24) g/L. A 3 x 2 factorial arrangement of treatments
      was used. In Exp. 1, 78 steers were individually fed the respective treatments
      for 106 d. Moisture added during tempering tended (linear; P < 0.10) to increase
      starch availability but linearly decreased (P < 0.01) particle size. Decreasing
      flake density increased (P < 0.001) starch availability and also decreased (P <
      0.001) particle size. Starch availability (P < 0.001), moisture (P < 0.001), and
      particle size (P = 0.05) were all greater for SFC that was collected the day of
      processing compared with SFC that had been processed the previous day. Steers fed
      diets containing SF24 consumed less DM as the moisture level increased, whereas
      steers fed diets containing SF28 had increased DMI as moisture level increased
      (moisture x FD interaction; P < 0.01). Nonetheless, ADG, G:F, and most carcass
      characteristics did not differ among treatments. In Exp. 2, 6 multicannulated
      Jersey steers were used in a 6 x 6 Latin square using the same treatments as in
      Exp. 1. Increasing moisture intake linearly decreased (P < 0.05) starch intakes.
      Organic matter and N intakes followed similar trends but were not different.
      Decreasing FD tended to increase (P < 0.10) microbial N flow to the duodenum and
      increased microbial efficiency (P < 0.05). Ruminal starch digestibility was
      90.5%, and total tract starch digestibility was 99.5% without adding moisture or
      processing beyond SF28. Moisture additions to corn before steam flaking resulted
      in few differences in performance or digestibility, despite increases in starch
      availability that occurred as moisture increased. Processing corn more
      extensively than SF28 may be unnecessary and cost-prohibitive.

PMID- 16424272
TI  - Effects of supplements that contain increasing amounts of metabolizable protein
      with or without Ca-propionate salt on postpartum interval and nutrient
      partitioning in young beef cows.
AB  - Cattle grazing winter range forages exhibit interannual variation in response to
      supplementation. This variation may be mediated by circulating concentrations and
      subsequent metabolism of glucose, which are influenced by forage quality and
      availability. A study conducted at the Corona Range and Livestock Research Center
      during 2 dry years evaluated responses of young postpartum beef cows (n = 51,
      initial BW = 408 +/- 3 kg, and BCS = 5.1 +/- 0.04 in year 1; n = 36, initial BW =
      393 +/- 4 kg, and BCS = 4.5 +/- 0.05 in year 2) to supplements that met or
      exceeded metabolizable protein (MP) requirements. Supplements were fed at 908 g/d
      per cow and provided 327 g of CP, 118 g of ruminally undegradable protein (RUP),
      and 261 g of MP from RUP (RMP), calculated to meet the MP requirement; 327 g of
      CP, 175 g of RUP, and 292 g of MP from RUP (RMP+), which supplied 31 g of excess
      MP; or 327 g of CP, 180 g of RUP, 297 g of MP from RUP, and 100 g of propionate
      salt (NutroCal, Kemin Industries, Inc., Des Moines, IA; (RMP+)P), which supplied
      36 g of excess MP. Body weights were recorded once every 2 wk, and blood samples
      were collected 1x/wk in year 1 and 2x/wk in year 2 for 100 d postpartum.
      Postpartum anestrous was evaluated by progesterone from weekly blood samples, and
      pregnancy was confirmed by rectal palpation at weaning. As MP from RUP with or
      without propionate increased, a decrease (P = 0.03) was observed in postpartum
      interval; however, differences in pregnancy percentage (P = 0.54) were not
      influenced by treatments. We hypothesized that additional AA from RUP along with
      propionate would increase supply of glucogenic precursors and, therefore,
      glucogenic potential of the diet. Therefore, a postpartum glucose tolerance test
      was conducted near the nadir of cow BW to evaluate the rate of glucose clearance.
      Glucose tolerance tests showed that (RMP+)- or (RMP+)P-supplemented cows had
      greater (P = 0.03) rates of glucose clearance, which might have influenced the
      observed abbreviation of the postpartum interval. A glucose tolerance test
      conducted at the end of supplemental treatments revealed no differences in
      glucose clearance (P = 0.47) among previously supplemented cows. These data
      suggest that not only vegetative quality, duration of lactation, and season of
      grazing, but also type of supplementation may play a pivotal role in the young
      postpartum beef cow's ability to respond and incorporate nutrients into insulin
      sensitive tissues.

PMID- 16424273
TI  - Effects of mild heat stress and grain challenge on acid-base balance and rumen
      tissue histology in lambs.
AB  - The effect of heat stress (HS) and grain challenge (GC) on acid-base balance and
      rumen tissue histology in lambs was investigated using 24 yearling wether lambs
      (58 +/- 4.5 kg of BW) in a 2 x 2 factorial experiment with repeated measures for
      day (10, 14, and 17) of sampling. The factors were temperature [thermoneutral
      zone (TN) vs. HS] and diet (control vs. GC). Lambs were blocked by BW and
      assigned to 1 of 4 treatments in temperature-controlled rooms: 1) TN (temperature
      = 18 to 20 degrees C; relative humidity = 30%; 2) TN + GC; 3) HS (temperature =
      35 degrees C for 9 h/d, 20 degrees C for 15 h/d; relative humidity = 40%); and 4)
      HS + GC. Venous blood samples were collected at 1800 on the first day of GC (d
      10), in the middle of GC (d 14), and at the end of the trial (d 17) by jugular
      venipuncture and analyzed for pH, gases, hematocrit, plasma ions, and total
      protein. After all measurements in live animals were taken on d 17, lambs were
      slaughtered, and tissue samples were obtained from the ventral sac of the rumen
      for histological assessment. Except for the concentration of plasma glucose (P =
      0.04) and total protein (P < 0.01), there were no (P > 0.05) diet x temperature
      interactions. With HS, the concentration of Na+ and Cl- in the control group
      decreased at d 14 and then increased by d 17, and respiration rates in the
      control group decreased linearly (P < 0.05). Compared with the control group,
      respiration rates and the concentration of Cl- in the GC lambs increased linearly
      over time, whereas the concentration of Na+ decreased linearly (P < 0.05) across
      time. Under HS, the partial pressure of carbon dioxide, total carbon dioxide, the
      partial pressure of oxygen and oxygen saturation, and the concentration of Mg2+,
      glucose, and HCO3- showed quadratic (P < 0.05) responses with time. In both
      treatments, DMI, base excess of extracellular fluid, base excess of blood, and
      standard bicarbonate increased linearly (P < 0.05), and hematocrit, plasma
      protein, Ca2+, anion gap, and plasma strong ion difference decreased linearly (P
      < 0.05) across day. Compared with the control group, the GC group had decreased
      papillae count in the ruminal ventral sac (1.3 vs. 1.5; P < 0.05). These results
      suggest that under HS the acidifying effects of GC on acid-base balance in lambs
      were counteracted in the short-term through respiratory adaptation.

PMID- 16424274
TI  - Pork quality attributes associated with bilateral carcass variation.
AB  - The objective of this study was to identify bilateral differences in pork carcass
      quality as influenced by single leg shackling and suspension of electrically
      stunned pigs. Fifty-six Genepacker x EB market barrows (118 kg) were rendered
      unconscious and insensible to pain via electrical stimulation. Pigs were then
      shackled and suspended by the right hind leg before exsanguination and remained
      suspended until scalding. Initial (45-min) pH values of the LM at the 10th to
      11th rib interface were different (P = 0.016); shackled side loins possessed a
      greater i.m. pH than those loins associated with the free side of the carcass
      (6.26 vs. 6.10). At 24 h postmortem, loins from the shackled side had lower (P <
      0.001) L* values than loins from the free side in both the sirloin (53.08 vs.
      57.61) and blade (54.61 vs. 57.09) regions. Additionally, b* values were greater
      (P < 0.001) for loins from the shackled side than loins from the free side in the
      center (13.81 vs. 13.01) and blade (14.72 vs. 13.68) regions, and in the blade
      region, a* values were greater (P < 0.001) in the LM from the shackled side than
      loins from the free side (7.37 vs. 6.26). Moreover, LM chops of loins from the
      shackled side that were aged 21 d were rated less (P < 0.05) tough (2.74 vs.
      3.95) and more (P < 0.05) juicy (4.24 vs. 3.19) than chops from the free-hanging
      side. However, these differences were not evident after 41 d aging. From the
      results of this study, it can be concluded that bilateral differences exist
      within the LM of a pork carcass and that these differences are likely associated
      with the single-leg shackling and suspension of electrically stunned pigs.

PMID- 16424275
TI  - Relationship between sexual behavior classifications of rams and lambs sired in a
      competitive breeding environment.
AB  - The objectives for this study were to 1) determine the relationship between
      sexual performance class and lambs sired in a competitive mating environment, and
      2) determine whether the male-oriented ram test is valid. Fifteen 2- to 3-yr-old
      whitefaced rams classified as female-oriented, with high or low sexual
      performance, or classified as male-oriented were used in a multiple-sire breeding
      arrangement. Five groups of approximately 200 ewes each were exposed for 21 d to
      3 rams per group consisting of 1 ram from each class. Rams were blocked for
      sexual class, and those with close genetic relationship were assigned to
      different pens. Genomic DNA was prepared from blood collected from 15 rams, 934
      ewes, and 1,757 lambs. Up to 4 microsatellite markers were used to determine a
      lamb's sire. Of 884 ewes with identifiable lambs (known sires), 178 ewes had
      single lambs, 408 had multiples sired by 1 ram, and 298 had multiples sired by
      more than 1 ram. The sexual partner preference test used to identify male
      oriented rams did not absolutely reflect their sexual performance during
      competitive breeding. In contrast to only mounting and servicing males in
      preference tests before breeding, male-oriented rams sired 480 lambs from 330
      ewes. Serving capacity tests predicted sexual performance of high and low sexual
      performance rams. High performance rams impregnated more ewes (499 vs. 258; P <
      0.05) and sired more lambs (756 vs. 357; P < 0.05) than did low performance rams,
      respectively. Low performance and male-oriented rams did not differ for ewes
      impregnated or lambs sired. We conclude that 1) sexual partner preference tests
      used to classify male-oriented rams were not absolute in reflecting their
      breeding performance in a competitive breeding environment; 2) serving capacity
      tests predicted that high performance rams would breed more ewes than low
      performance rams and sire more lambs than either low performance or male-oriented
      rams; and 3) under the conditions of this study, low performance and male
      oriented rams did not have an adverse impact on the overall breeding outcome.
      Combined, low performance and male-oriented rams sired 81 more lambs than did
      high performance rams, but this required twice as many rams to obtain
      approximately equal breeding results. Therefore, we suggest that serving capacity
      tests should be used to select high performance rams, reduce number of rams with
      marginal sexual performance, and make decisions on ram numbers needed.

PMID- 16424276
TI  - Effects of season and breed on the feeding behavior of multiparous lactating sows
      in a tropical humid climate.
AB  - The effects of breed and season on performance and feeding behavior were studied
      during 76 lactations in multiparous Large White (LW; n = 17) and Creole (CR; n =
      23) sows reared in a humid tropical climate. The experiment was conducted in
      Guadeloupe (French West Indies, latitude 16 degrees N, longitude 61 degrees W)
      between May 2002 and July 2004. Average daily ambient temperature was greater
      during the hot season than during the warm season (26.0 vs. 23.8 degrees C), but
      relative humidity was similar in both seasons (85% on average). The daily
      fluctuations of ambient temperature and relative humidity were similar for both
      seasons. At farrowing, BW was lower (187 vs. 265 kg) and backfat thickness was
      greater (40 vs. 22 mm) in CR than in LW sows (P < 0.01). Sows were offered feed
      ad libitum between the fifth and the 26th day of lactation. There was a breed x
      season interaction (P < 0.05) for ADFI. During the hot season the reduction of
      ADFI was more pronounced in LW than in CR sows (-1,100 vs. -300 g/d).
      Irrespective of breed and season, the daily number of meals was 9.0. The meal
      size and the rate of feed intake were greater in LW than in CR sows, respectively
      (555 g and 153 g/min vs. 390 g and 83 g/min; P < 0.01). The diurnal proportion of
      ADFI was greater in CR than in LW sows (0.60 vs. 0.41; P < 0.01). The reduction
      in ADFI in LW sows during the hot season was mainly related to a reduction in
      feed intake during the day rather than during the night (-1.3 vs. -0.2 kg; P <
      0.01). Duration of standing was not affected by breed or season, and it averaged
      120 min/day. This study confirms the negative effect of the hot season on feeding
      behavior of lactating sows. It also suggests a better acclimation to daily high
      temperatures and a greater heat tolerance in CR compared with LW sows, at least
      for eating behavior.

PMID- 16424277
TI  - Incorporation of thymol into corncob granules for reduction of odor and pathogens
      in feedlot cattle waste.
AB  - Confined animal feeding operations can be a source of odor emissions, global
      warming gases, water pollution, and food contamination. Laboratory studies have
      indicated that plant oils with antimicrobial activity can be used to control
      pathogens and odor emissions from cattle and swine wastes. However, these oils
      are aromatic and may volatilize when applied topically. Our objectives were to
      evaluate the volatility of thymol from a feedlot surface and the effectiveness of
      topically applying thyme oil (2.5% thymol), incorporated into corncob granules
      and added once per week, to control odor emissions and total coliforms in feedlot
      manure. In the first study, thymol either volatilized or was degraded within 28 d
      after topical application. In a second study, thyme oil (2.5% thymol) was
      incorporated into corncobs and applied to pen surfaces weekly. Manure samples
      from 6 locations in each pen were collected from 3 untreated and 3 thymol-corncob
      treated pens (15 x 150 m; fifty 400-kg cattle/pen), 3 times per week for 8 wk.
      Samples were analyzed for thymol concentration, total VFA, branched-chain VFA,
      aromatic compounds, and the number of Escherichia coli and total coliform
      bacteria. Over the 8 wk, with the exception of wk 7, the desired thymol
      concentration of 15 to 20 micromol/g DM was maintained in the manure.
      Concentrations of VFA and branched chain-VFA increased over time in untreated and
      treated pens. However, the rate of VFA accumulation in treated pens (7.5 +/- 1.3
      micromol.g DM(-1).wk(-1)) was less (P < 0.01) than the rate of accumulation in
      untreated pens (18.0 +/- 2.1 micromol.g DM(-1).wk(-1)). Likewise, the rate of
      branched-chain VFA accumulation in treated pens (0.31 +/- 0.04 micromol.g DM(
      1).wk(-1)) was less (P < 0.01) than in untreated pens (0.55 +/- 0.06 micromol.g
      DM(-1).wk(1)). The concentrations of E. coli in treated pens (2.9 +/- 1.2 x 10(5)
      cfu.g DM(-1)) were 91% less (P < 0.04) than in untreated pens (31.1 +/- 4.0 x
      10(5) cfu.g DM(-1)). Similarly, concentrations of coliforms in treated pens (3.7
      +/- 1.3 x 10(5) cfu.g DM(-1)) were 89% less (P < 0.04) than those of untreated
      pens (35.3 +/- 4.2 x 10(5) cfu.g DM(-1)). These results indicate that odor
      emissions and total coliforms can be reduced in feedlot manure with a once per
      week application of thymol incorporated in a granular form. However, corncobs are
      bulky, and other granular carriers with a greater carrying capacity for thyme oil
      should be explored.

PMID- 16424278
TI  - Use of treatment records and lung lesion scoring to estimate the effect of
      respiratory disease on growth during early and late finishing periods in South
      African feedlot cattle.
AB  - Growth, morbidity, and slaughter data from 2,036 calves in 2 South African
      feedlots were used to estimate the effect of bovine respiratory disease (BRD) and
      of lung lesion type and extent on growth during the early (processing to d 35)
      and late (d 35 to slaughter) finishing periods. Calves were weighed at processing
      (d 5 after arrival), on d 35, and at slaughter after a mean of 137 d on feed. All
      calves were monitored twice daily and were treated for BRD if rectal temperature
      was > 40 degrees C or if other specific signs of BRD were present. After
      slaughter, the occurrence and extent of parenchymal bronchopneumonic lesions and
      pleural adhesions were recorded. Subclinical BRD (never treated but with lung
      lesions at slaughter) occurred in 29.7% and clinical BRD in 22.6% of calves. Lung
      lesions were present in 43% of calves at slaughter; 8.6% had parenchymal lesions
      and 38.8% had pleural adhesions. Using a combined case definition (treated for
      BRD and/or lung lesions present at slaughter), the incidence of BRD was 52.5%.
      During the early finishing period, clinical BRD reduced ADG by 216 g (P < 0.001),
      subclinical BRD reduced ADG by 91 g (P < 0.001), and the combined effect of BRD
      was a 143 g reduction in ADG (P < 0.001). After d 35, animals treated for BRD
      tended to grow faster than those with subclinical BRD (P = 0.11), indicating that
      treatment was generally successful in reducing economic losses. The extent of
      bronchopneumonic lesions at slaughter was not associated with reduced growth
      during the early finishing period (P = 0.27), but extensive lesions reduced ADG
      by 88 g during the late period (P = 0.02). In contrast, the extent of pleural
      adhesions was not associated with reduced growth rate during the late finishing
      period (P = 0.37) but was strongly associated with reduced ADG before d 35; there
      was a 101 g reduction (P < 0.001) and a 220 g reduction (P = 0.01) for adhesions
      involving < 50% and > 50% of the pleural surfaces, respectively. Thus, although
      the presence of bronchopneumonic lesions and pleural adhesions at slaughter were
      both associated with reductions in overall ADG, they were indicative of
      production losses having occurred at different times during the finishing period.
      The overall effect of BRD was a 24 g reduction in ADG (P = 0.02) and a 5.1 d
      increase in days on feed (P < 0.001). The hidden cost of reduced growth rate due
      to BRD amounted to $3.41 per calf with clinical or subclinical BRD, or $1.79 per
      animal entering the feedlot.

PMID- 16424280
TI  - Response to Cellerino on annual killifishes.

PMID- 16424279
TI  - Effects of canola seed supplementation on intake, digestion, duodenal protein
      supply, and microbial efficiency in steers fed forage-based diets.
AB  - Fourteen Holstein steers (446 +/- 4.4 kg of initial BW) with ruminal, duodenal,
      and ileal cannulas were used in a completely randomized design to evaluate
      effects of whole or ground canola seed (23.3% CP and 39.6% ether extract; DM
      basis) on intake, digestion, duodenal protein supply, and microbial efficiency in
      steers fed low-quality hay. Our hypothesis was that processing would be necessary
      to optimize canola use in diets based on low-quality forage. The basal diet
      consisted of ad libitum access to switchgrass hay (5.8% CP; DM basis) offered at
      0700 daily. Treatments consisted of hay only (control), hay plus whole canola (8%
      of dietary DM), or hay plus ground canola (8% of dietary DM). Supplemental canola
      was provided based on the hay intake of the previous day. Steers were adapted to
      diets for 14 d followed by a 7-d collection period. Total DMI, OM intake, and OM
      digestibility were not affected (P > or = 0.31) by treatment. Similarly, no
      differences (P > or = 0.62) were observed for NDF or ADF total tract digestion.
      Bacterial OM at the duodenum increased (P = 0.01) with canola-containing diets
      compared with the control diet and increased (P = 0.08) in steers consuming
      ground canola compared with whole canola. Apparent and true ruminal CP
      digestibilities were increased (P = 0.01) with canola supplementation compared
      with the control diet. Canola supplementation decreased ruminal pH (P = 0.03)
      compared with the control diet. The molar proportion of acetate in the rumen
      tended (P = 0.10) to decrease with canola supplementation. The molar proportion
      of acetate in ruminal fluid decreased (P = 0.01), and the proportion of
      propionate increased (P = 0.01), with ground canola compared with whole canola.
      In situ disappearance rate of hay DM, NDF, and ADF were not altered by treatment
      (P > or = 0.32). In situ disappearance rate of canola DM, NDF, and ADF increased
      (P = 0.01) for ground canola compared with whole canola. Similarly, ground canola
      had greater (P = 0.01) soluble CP fraction and CP disappearance rate compared
      with whole canola. No treatment effects were observed for ruminal fill, fluid
      dilution rate, or microbial efficiency (P > or = 0.60). The results suggest that
      canola processing enhanced in situ degradation but had minimal effects on ruminal
      or total tract digestibility in low-quality, forage-based diets.

PMID- 16424281
TI  - Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric
      restriction and other models of longevity.
AB  - Dietary restriction of calories (caloric restriction [CR]) increases longevity in
      phylogenetically diverse species. CR retards or prevents age-dependent
      deterioration of tissues and an array of spontaneous and chemically induced
      diseases associated with obesity including cardiovascular disease, diabetes, and
      cancer. An understanding of the molecular mechanisms that underlie the beneficial
      effects of CR will help identify novel dietary, pharmacological, and lifestyle
      strategies for slowing the rate of aging and preventing these diseases as well as
      identify factors which modulate chemical toxicity. Here, we review the
      involvement of transcriptional coactivator proteins, peroxisome proliferator
      activated receptor (PPAR) gamma coactivator 1 (PGC-1) alpha and beta, and
      regulated nuclear receptors (NR) in mediating the phenotypic changes found in
      models of longevity which include rodent CR models and mouse mutants in which
      insulin and/or insulin-like growth factor-I signaling is attenuated. PGC-1alpha
      is transcriptionally or posttranslationally regulated in mammals by: 1) forkhead
      box "other" (FoxO) transcription factors through an insulin/insulin-like growth
      factor-I -dependent pathway, 2) glucagon-stimulated cellular AMP (cAMP) response
      element binding protein, 3) stress-activated kinase signaling through p38 mitogen
      activated protein kinase, and 4) the deacetylase and longevity factor sirtuin 1
      (SIRT1). PGC-1alpha and PGC-1beta regulate the ligand-dependent and -independent
      activation of a large number of NR including PPARalpha and constitutive activated
      receptor (CAR). These NR regulate genes involved in nutrient and xenobiotic
      transport and metabolism as well as resistance to stress. CR reverses age
      dependent decreases in PGC-1alpha, PPARalpha, and regulated genes. Strategies
      that target one or multiple PGC-1-regulated NR could be used to mimic the
      beneficial health effects found in models of longevity.

PMID- 16424282
TI  - Housing density does not influence the longevity effect of calorie restriction.
AB  - This study examined the effect of housing density on the longevity-extending and
      disease-delaying actions of calorie restriction (CR). Singly or multiply housed
      (four per cage) mice were either fed ad libitum (AL) or were on CR beginning at 2
      months. All CR mice were fed 40% less food than were multiply housed AL mice. CR
      increased median longevity by 19%, and housing density had no effect on this
      increase. CR also reduced neoplastic lesions in both housing groups, but
      lymphoma, the most common neoplasm, was reduced more in singly than in multiply
      housed mice. Singly housed AL mice ate 40% more food than did multiply housed AL
      mice, but weighed the same and lived as long as multiply housed AL mice. These
      results indicate that CR can extend life span as effectively in multiply as in
      singly housed mice, even though housing density can differentially affect the
      cancer-reducing effect of CR.

PMID- 16424283
TI  - Reference body composition in adult rhesus monkeys: glucoregulatory and
      anthropometric indices.
AB  - Rhesus monkeys have been used as models to study obesity and disease. The aim of
      this study was to define body mass indices for underweight and obesity in rhesus
      monkeys. Longitudinal data collected over 8-14 years from 40 male and 26 female
      rhesus monkeys were analyzed. Body weight, insulin sensitivity index, and
      disposition index were regressed against percent body fat (%BF). A minimal %BF
      beyond which further loss of body weight resulted in loss of lean mass was
      determined to be 11.5% in older males, 8% in adult females, and 9% in younger
      adult males. Insulin sensitivity index and disposition index reached minimum
      values at 23% fat in older males, 18% in adult females, and 21% in younger adult
      males, indicating obesity. The estimated reference range for %BF was 9%-23% in
      male and 8%-18% in female monkeys, corresponding to body mass indices of 32-44
      kg/m(2) for male and 27-35 kg/m(2) for female monkeys.

PMID- 16424284
TI  - Association of interleukin-10 promoter single nucleotide polymorphisms -819 T/C
      and -592 A/C with aging.
AB  - Increased inflammatory activity is known to accompany aging. Single nucleotide
      polymorphisms of inflammatory mediator genes might therefore affect the aging
      process. Relation of eight SNPs (tumor necrosis factor-alpha [TNF-alpha] -1031
      T/C, interleukin-10 [IL-10] -819 T/C, IL-1beta -511 C/T, IL-6 -634 C/G, IL-18 
      607 A/C, transforming growth factor-beta [TGF-beta] +869 C/T, matrix
      metalloproteinase-1 [MMP-1] -1607 1G/2G, and MMP-3 -1171 5A/6A) with age or
      gender was evaluated in 500 Japanese persons (mean age: 56.7 years old, range: 19
      100) by the chi-square test. There was a significant association of IL-10 -819
      T/C with age (p =.0026). The association remained significant after multivariate
      logistic regression analysis (odds ratio for an age interval for 1 year, 1.009;
      95% CI, 1.002-1.016). Furthermore, the genotype distribution of IL-10 -819 T/C
      was completely consistent with that of -592 A/C. These data suggest that IL-10 
      819 T/C and -592 A/C may be a promising candidate for an aging-related gene in a
      Japanese population.

PMID- 16424286
TI  - Foot and ankle characteristics associated with impaired balance and functional
      ability in older people.
AB  - BACKGROUND: Ageing is associated with changes to the structure and function of
      the foot and ankle, and there is preliminary evidence that foot problems impair
      balance and increase the risk of falls. To explore this in more detail, we
      conducted a study to determine the relative contribution of several foot and
      ankle characteristics to performance on a range of balance and functional tests.
      METHODS: One hundred seventy-six people (56 men and 120 women, mean age 80.1
      years, standard deviation 6.4 years) residing in a retirement village underwent
      tests of foot and ankle characteristics (including foot posture, range of motion,
      strength, and deformity), sensorimotor function (including vision, sensation,
      strength, and reaction time), and balance and functional ability (including tests
      of standing balance, leaning balance, stepping, sit-to-stand, and walking speed).
      RESULTS: Many foot and ankle characteristics and sensorimotor measures were
      associated with performance on the balance and functional tests in univariate
      analyses. Multiple regression analysis consistently revealed that ankle
      flexibility, plantar tactile sensitivity, and toe plantarflexor strength were
      significant and independent predictors of balance and functional test
      performance, explaining up to 59% of the variance in these test scores.
      CONCLUSIONS: Foot and ankle characteristics, particularly ankle flexibility,
      plantar tactile sensation, and strength of toe plantarflexor muscles, are
      significant independent predictors of balance and functional ability in older
      people. Programs to improve the strength and flexibility of the foot and
      interventions to augment plantar sensation may be beneficial in improving
      mobility and reducing the risk of falls.

PMID- 16424287
TI  - Time requirement for young and elderly women to move into a position for breaking
      a fall with outstretched hands.
AB  - BACKGROUND: Risk for hip fracture during a fall is reduced by contacting the
      ground first with the outstretched hands. However, it is unclear whether the time
      required for young and elderly individuals to move the hands into a protective
      position exceeds that available during a typical fall. METHODS: We tested whether
      young (n = 30; aged 18-35 years) and elderly women (n = 30; aged 70-88 years)
      differed in the time required to move their hands into a protective position for
      breaking a fall. Participants stood either facing or sideways to shoulder-height
      targets (simulating forward and sideways falls, respectively), which they were
      instructed to contact as quickly as possible after hearing an aural go cue. Total
      contact time was partitioned into reaction time and movement time. RESULTS: Young
      women contacted the targets faster than elderly women in both forward (530 +/- 60
      vs 615 +/- 88 ms; p <.001) and sideways trials (658 +/- 80 vs 799 +/- 145 ms; p
      <.001). This difference was due to faster movement times for young participants.
      There was no difference between groups in reaction time. CONCLUSIONS: Previous
      studies have shown that during actual falls from standing, wrist and pelvis
      contact occur at 680 +/- 116 and 715 +/- 160 ms, respectively. Comparing these
      values to our results suggests that the typical elderly woman should be able to
      move her hands quickly enough to break a forward fall, but not a sideways fall.

PMID- 16424288
TI  - Age differences in timed accurate stepping with increasing cognitive and visual
      demand: a walking trail making test.
AB  - BACKGROUND: Impaired vision, cognition, and divided attention performance predict
      falls. Requiring both visual and cognitive input, the ability to step accurately
      is necessary to safely traverse challenging terrain conditions such as uneven or
      slippery surfaces. We compared healthy young and older adults in the time taken
      to step accurately under conditions of increasing cognitive and visual demand.
      METHODS: Healthy Young (n = 42, mean age 21) and Older (n = 37, mean age 70)
      participants were required to step accurately on an instrumented walkway under
      conditions of increasing visual and cognitive demand. Based on the paper-and
      pencil neuropsychological test, the Trail Making Test (P-TMT) A and B,
      participants stepped on instrumented targets with increasing sequential numbers
      (Walking Trail Making Test A [W-TMT A]) and increasing sequential numbers and
      letters (Walking Trail Making Test B [W-TMT B]), under conditions of Low as well
      as Normal lighting. RESULTS: W-TMT performance time increased with increased age
      (Older vs Young), decreased light (Low vs Normal), and increased cognitive demand
      (Trails B vs Trails A). W-TMT performance time was disproportionately increased
      in Low light and in the Older group under the highest cognitive demand (W-TMT B)
      conditions. Paired W-TMT A-B differences were three times higher in the Older
      group than in the Young group. In the Older group, the correlation between W-TMT
      results and P-TMT B was particularly strong (p <.001). CONCLUSIONS: The time to
      perform a stepping accuracy task, such as may be required to avoid environmental
      hazards, increases under reduced lighting and with increased cognitive demand,
      the latter disproportionately so in older adults.

PMID- 16424285
TI  - Risk factors for falls in older disabled women with diabetes: the women's health
      and aging study.
AB  - BACKGROUND: The aim of this study was to determine whether older disabled women
      with diabetes have an increased risk of falls compared to women without diabetes
      and to identify fall risk factors among this high-risk subgroup of patients.
      METHODS: Data are from the Women's Health and Aging Study I (n = 1002, age > or =
      65 years), a prospective, population-based cohort study of the one third most
      disabled women in the Baltimore (MD) urban community-dwelling population.
      Participants were followed semiannually for 3 years. Falls were ascertained at
      each interview. Diabetes was ascertained by means of a standardized algorithm
      using multiple sources of information. RESULTS: Baseline prevalence of diabetes
      was 15.5%. Of the 878 women who participated in at least one follow-up visit and
      were able to walk at baseline, 64.9% fell at least once during the study and
      29.6% experienced two or more falls during a follow-up interval. After adjustment
      for traditional risk factors, women with diabetes had a higher probability of any
      fall (odds ratio [OR] 1.38; 95% confidence interval [CI], 1.04-1.81) and of
      falling two or more times during a follow-up interval (OR 1.69; CI, 1.18-2.43),
      compared with women without diabetes. Among diabetic women, presence of
      widespread musculoskeletal pain (OR 5.58; CI, 1.89-16.5), insulin therapy (OR
      2.02; CI, 1.10-3.71), overweight (OR 3.50; CI, 1.21-10.1), and poor lower
      extremity performance (OR 7.76; CI, 1.03-58.8) were independently associated with
      increased likelihood of recurrent falls, after adjusting for major risk factors.
      There were synergistic effects of diabetes and lower-extremity pain and also
      diabetes and body mass index levels on the risk of falling (p for interactions
      <.05). CONCLUSION: Even among disabled older women diabetes is associated with an
      increased risk of falling, independent of established fall risk factors. In this
      specific group of older women, pain, high body mass index, and poor lower
      extremity performance are powerful predictors of falling.

PMID- 16424289
TI  - Are preoperative depressive symptoms associated with postoperative delirium in
      geriatric surgical patients?
AB  - BACKGROUND: Delirium is common in older surgical patients and predicts negative
      health outcomes. Whether depressive symptoms are prevalent and predict the
      development of postoperative delirium in elderly surgical patients has not been
      investigated. Our study aimed to examine the prevalence and prognostic importance
      of preoperative depressive symptoms in older surgical patients. METHODS: Patients
      at least 65 years of age who were scheduled for major noncardiac surgery were
      recruited. Preoperatively, patients were screened for symptoms of depression
      using the 15-point Geriatric Depression Scale (GDS). Postoperative delirium was
      measured using the Confusion Assessment Method. The associations between
      covariates and preoperative depression, and postoperative delirium were
      determined by multivariate logistic regression. RESULTS: In the 219 patients
      studied, the mean age was 73.6 +/- 6 years, 12% of patients reported six or more
      depressive symptoms, and 32% reported three to five depressive symptoms. By
      multivariate logistic regression, patient characteristics associated with six or
      more symptoms of depression included <12 years of education, moderate to severe
      limitation in functional status, and drinking more than two alcoholic beverages
      per day. Postoperatively, 46% of patients developed delirium. Patients with a
      greater number of preoperative depressive symptoms were more likely to develop
      postoperative delirium (p =.048) and experience a longer duration of
      postoperative delirium (p =.027). Even after adjusting for covariates associated
      with depression and postoperative delirium--including age, educational level,
      functional status, and preoperative alcohol use--patients with more than six
      preoperative depressive symptoms were still significantly more likely to have a
      longer duration of postoperative delirium than did those patients with fewer than
      two depressive symptoms (odds ratio = 2.69, confidence interval = 1.04-6.93).
      CONCLUSION: Preoperative screening for the presence of depressive symptoms can be
      performed easily in elderly patients, and yields useful prognostic information
      relating to postoperative delirium.

PMID- 16424291
TI  - Elderly patients with cognitive impairment have a high risk for functional
      decline during hospitalization: The GIFA Study.
AB  - BACKGROUND: We tested the hypothesis that cognitive impairment upon admission
      (CIA) and cognitive decline (CD) during hospitalization are associated with an
      increased risk for functional decline (FD) in older inpatients. METHODS: The
      Italian Group of Pharmacoepidemiology in the Elderly (Gruppo Italiano di
      Farmacoepidemiologia nell'Anziano, GIFA) project was a multicenter survey of 9061
      older patients admitted to Italian hospitals between 1991 and 1997. CIA was
      defined as a Hodkinson Abbreviated Mental Test score <7 on admission. The
      percentage of participants who developed FD, defined as loss of the ability to
      perform without help one or more activities of daily living between admission and
      discharge, was compared in patients who did and did not have CIA, and between
      those who lost at least one point in Hodkinson Abbreviated Mental Test score (CD)
      and those who did not. RESULTS: Mean age was 77.4 years, and women represented
      52.3% of the sample. CIA was present in 21.0% of the patients. During
      hospitalization, 176 patients (1.9%) experienced FD (4% of those with CIA vs 1.3%
      of those without CIA). In multivariate analysis, CIA was an important risk factor
      for FD (odds ratio 2.4; 95% confidence interval, 1.7-3.5; p <.001), independent
      of age, gender, comorbidity, polypharmacy, and disability on admission. CD
      occurred in 3.7% of the sample and was strongly associated with an increased risk
      for FD (odds ratio 16.0; 95% confidence interval, 10.8-23.6; p <.001).
      CONCLUSIONS: Elderly patients with CIA have a higher risk for FD. New strategies
      should be implemented to prevent FD in patients with cognitive impairment, who
      account for a high percentage of older persons who are admitted to hospitals.

PMID- 16424290
TI  - Identification of pain-reduction strategies used by community-dwelling older
      persons.
AB  - BACKGROUND: The types of methods used by older persons to reduce chronic pain
      have not been adequately characterized. In this cross-sectional study of older
      persons with chronic nonmalignant pain, we sought to identify strategies
      perceived as effective in reducing pain and to ascertain factors associated with
      their use. METHODS: Participants included 272 community-dwelling persons aged 73
      years or older. Information regarding participants' sociodemographic, clinical,
      psychological, and pain status was collected. Strategies perceived as effective
      in reducing pain were identified using a qualitative approach. Similar methods
      (e.g., "takes acetaminophen when necessary" and "uses Tramadol daily") were
      grouped into specific pain-reduction categories (e.g., analgesic medication use).
      Logistic regression analysis was used to identify associations between
      participant-related factors and the four most prevalent pain-reduction
      strategies. RESULTS: Participants had a mean (standard deviation) age of 80.9
      (5.1) years and were mostly female (69%). Overall, 248 (91%) participants
      reported at least one effective strategy for reducing pain; the mean number of
      strategies per participant was 2.7 (range = 1-6). The four most prevalent pain
      reduction strategies were analgesic medication use (reported by 59% of
      participants), activity restriction (38%), hot and/or cold modalities (28%), and
      exercise (23%). Although most participants reported at least one effective pain
      reduction strategy, 60% rated their pain as "quite a bit" or "extremely"
      bothersome. In logistic regression analysis, no factor (including age and gender)
      was independently associated with any of the prevalent pain-reduction strategies.
      CONCLUSIONS: Despite the fact that most participants perceived several pain
      reduction strategies as effective, 60% reported experiencing substantial pain.
      Research of older persons with chronic pain is warranted to determine whether
      changes in the way existing pain-reduction strategies are administered can
      improve the management of pain or if more efficacious strategies are needed.

PMID- 16424292
TI  - Delayed postprandial gastric emptying and impaired gallbladder contraction
      together with elevated cholecystokinin and peptide YY serum levels sustain
      satiety and inhibit hunger in healthy elderly persons.
AB  - BACKGROUND: Altered gastric and cholecystic motility are risk factors for
      malnutrition in elderly persons, mainly through impaired satiety-appetite rhythm.
      Contrasting data have been published about this topic. The aim of this study was
      to evaluate, in healthy elderly participant, postprandial gastric and cholecystic
      emptying in relation to serum CCK (cholecystokinin) and PYY (peptide YY), as well
      as satiety and hunger sensations. METHODS: We studied 10 community-dwelling
      elderly persons, (77 +/- 3 years old) and 9 younger adult persons (32 +/- 8 years
      old). Using ultrasonography, we measured gastric antrum area and cholecystic
      volume in fasting condition and after an 800-kcal mixed meal. Time for gastric
      and cholecystic emptying, and percentage of cholecystic emptying were calculated.
      Satiety and hunger were evaluated every 30 minutes using visual analogue scales.
      CCK and PYY serum levels were assayed 30 minutes before and at times 0, 30, 60,
      120, and 240 minutes after the meal. RESULTS: Elderly participants showed a
      longer gastric emptying time compared to younger participants (448 +/- 104 vs 306
      +/- 57 minutes, p <.002). Postprandial cholecystic emptying was significantly
      reduced in the older group (maximum contraction, 69% vs 84%; p <.05). After the
      meal, CCK and PYY levels showed higher, persistent elevation in elderly
      participants. In this group, postprandial satiety lasted significantly longer
      than in younger participants, and hunger was suppressed throughout the
      postprandial period. Antral area directly correlated with satiety and inversely
      with hunger. Gallbladder volume inversely correlated to satiety. CONCLUSIONS:
      This study showed, in a group of healthy elderly people, delayed gastric emptying
      associated to reduced cholecystic contractility together with higher CCK and PYY
      serum levels. These modifications facilitated long-lasting satiety and hunger
      suppression after a meal. This condition may lead to caloric restriction and
      finally to malnutrition at older ages.

PMID- 16424293
TI  - Six-week improvements in muscle mass and strength during androgen therapy in
      older men.
AB  - BACKGROUND: The purpose of our study was to assess the early effects of a potent
      anabolic androgen on muscle mass and strength, lower extremity power, and
      functional performance in older men. METHODS: Thirty-two men 72 +/- 6 years of
      age were randomized to receive oxandrolone (10 mg twice daily) or matching
      placebo in a 2:1 manner for 12 weeks. Total and appendicular lean body mass (LBM)
      were assessed by dual-energy x-ray absorptiometry (DEXA). Lower extremity muscle
      volume was determined by magnetic resonance imaging to validate DEXA changes.
      RESULTS: Total LBM increased by 2.7 +/- 1.6 kg after 6 weeks with oxandrolone (p
      <.001), which was greater (p <.001) than the decline in LBM (-0.5 +/- 0.9 kg)
      with placebo. Appendicular LBM increased by 1.2 +/- 0.9 kg after just 6 weeks
      with oxandrolone (p <.001), which was greater (p <.001) than the decline in LBM (
      0.4 +/- 0.5 kg) with placebo. These changes were >90% of the gains in total and
      appendicular LBM (3.0 +/- 1.5 kg and 1.3 +/- 0.9 kg, respectively) after 12
      weeks. Total thigh and hamstring muscle volume increased by 111 +/- 29 mm(3) (p
      =.001) and 75 +/- 18 mm(3) (p =.001), respectively, after 12 weeks. Maximal
      strength increased for the leg press 6.3 +/- 5.6% (p =.003), leg curl 6.7 +/-
      8.6% (p =.01), chest press 6.9 +/- 6.5% (p =.001), and latissimus pull-down 4.8
      +/- 6.3% (p =.009) with oxandrolone after 6 weeks; these increases were different
      than those with placebo (p <.001) and were 93%, 96%, 74%, and 94% of the
      respective gains at week 12. There were no improvements in functional measures.
      CONCLUSION: Treatment with a potent anabolic androgen may produce significant
      increases in muscle mass and strength after only 6 weeks in healthy older men.
      However, such treatment did not improve leg muscle power or walking speed.

PMID- 16424294
TI  - Aldosterone and telomere length in white blood cells.
AB  - BACKGROUND: Aldosterone accelerates cardiovascular aging by mechanisms that
      generate reactive oxygen species. Telomere length in white blood cells (WBCs) may
      be a bioindicator that registers the accruing burden of systemic oxidative
      stress. The aim of the present study was, therefore, to examine the relationship
      between plasma aldosterone and telomere length in WBCs. METHODS: We studied 75
      normotensive and never-treated mildly hypertensive men whose blood was drawn for
      the measurements of plasma aldosterone concentration and the terminal restriction
      fragment (TRF) length in WBCs. RESULTS: The slope of the TRF-age relationship in
      the entire cohort showed a decrease in telomere length of 26 +/- 5 base pairs per
      year (r = -0.46, p <.001). Age-adjusted TRF length was the longest in the lowest
      aldosterone quartile (6.74 +/- 0.12 kb) and shortest in the highest aldosterone
      quartile (6.36 +/- 0.11 kb), with intermediate TRF lengths in the second and
      third aldosterone quartiles (analysis of variance [ANOVA] trend test, p =.025).
      In telomeric attrition equivalence, participants in the upper aldosterone
      quartile were 15 years older than their peers in the lowest quartile.
      CONCLUSIONS: The inverse relationship between aldosterone and WBC telomere length
      suggests not only that aldosterone is pro-oxidant but that elevated
      concentrations of this hormone might be linked to a higher rate of telomere
      attrition and perhaps increased biological aging in humans.

PMID- 16424295
TI  - Drug treatment of systolic and of diastolic heart failure in elderly persons.
AB  - Underlying causes, risk factors, and precipitating causes of heart failure (HF)
      should be treated. Patients with HF and an abnormal left ventricular ejection
      fraction (systolic HF) or normal left ventricular ejection fraction (diastolic
      HF) should be treated with diuretics if fluid retention is present, with an
      angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker
      if the patient cannot tolerate an ACE inhibitor because of cough, angioneurotic
      edema, rash, or altered taste sensation, and with a beta blocker unless
      contraindicated. If severe systolic HF persists, an aldosterone antagonist should
      be added. If HF persists, isosorbide dinitrate plus hydralazine should be added.
      Calcium channel blockers should be avoided if systolic HF is present. Digoxin
      should be avoided in men and women with diastolic HF if sinus rhythm is present
      and in women with systolic HF. Digoxin should be given to men with systolic HF if
      symptoms persist, but the serum digoxin level should be maintained between 0.5
      and 0.8 ng/ml. Cardiac synchronized pacing should be considered in patients with
      severe systolic HF despite optimal medical therapy, with sinus rhythm, and with
      ventricular dyssynchrony.

PMID- 16424296
TI  - Cerebrovascular disease and executive dysfunction in geriatric depression.

PMID- 16424297
TI  - Explaining the color distributions of globular cluster systems in elliptical
      galaxies.
AB  - The colors of globular clusters in most large elliptical galaxies are bimodal.
      This is generally taken as evidence for the presence of two cluster
      subpopulations that have different geneses. However, here we find that, because
      of the nonlinear nature of the metallicity-to-color transformation, a coeval
      group of old clusters with a unimodal metallicity spread can exhibit color
      bimodality. The models of cluster colors indicate that horizontal-branch stars
      are the main drivers behind the empirical nonlinearity. We show that the scenario
      gives simple and cohesive explanations for all the key observations and could
      simplify theories of elliptical galaxy formation.

PMID- 16424298
TI  - Transient homologous chromosome pairing marks the onset of X inactivation.
AB  - Mammalian X inactivation turns off one female X chromosome to enact dosage
      compensation between XX and XY individuals. X inactivation is known to be
      regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also
      be regulated in trans to ensure mutually exclusive silencing. Here, we
      demonstrate that interchromosomal pairing mediates this communication. Pairing
      occurs transiently at the onset of X inactivation and is specific to the X
      inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice,
      whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X
      autosome interactions inhibit endogenous X-X pairing and block the initiation of
      X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans.
      We propose that Tsix and Xite regulate counting and mutually exclusive choice
      through X-X pairing.

PMID- 16424300
TI  - Acts of God?

PMID- 16424299
TI  - The Ste5 scaffold allosterically modulates signaling output of the yeast mating
      pathway.
AB  - Scaffold proteins organize signaling proteins into pathways and are often viewed
      as passive assembly platforms. We found that the Ste5 scaffold has a more active
      role in the yeast mating pathway: A fragment of Ste5 allosterically activated
      autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting
      form of Fus3 is partially active-it is phosphorylated on only one of two key
      residues in the activation loop. Unexpectedly, at a systems level, autoactivated
      Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation
      and a decrease in pathway transcriptional output. Thus, scaffolds not only direct
      basic pathway connectivity but can precisely tune quantitative pathway input
      output properties.

PMID- 16424301
TI  - Avian influenza. Amid mayhem in Turkey, experts see new chances for research.

PMID- 16424303
TI  - Cosmology. Astronomers push and pull over dark energy's role in cosmos.

PMID- 16424302
TI  - Avian influenza. WHO proposes plan to stop pandemic in its tracks.

PMID- 16424305
TI  - Nonproliferation. India struggles to put its nuclear house in order.

PMID- 16424304
TI  - Psychology. Hunter-gatherers grasp geometry.

PMID- 16424306
TI  - CNRS shakeup. France's basic science agency hopes new lineup will resolve crisis.

PMID- 16424307
TI  - South Korean science. Armed with cash, institute chief launches an education
      'blitzkrieg'.

PMID- 16424308
TI  - Scientific publishing. Hwang aftereffects reverberate at journals.

PMID- 16424310
TI  - Archaeology. Rising water poses threat to Egypt's antiquities.

PMID- 16424309
TI  - Drug development. Drugs inspired by a drug.

PMID- 16424311
TI  - Archaeology. Archaeological pharaoh sets determined course for Egypt.

PMID- 16424312
TI  - Biomedical training programs. NIH told to get serious about giving minorities a
      hand.

PMID- 16424313
TI  - Biomedical training programs. Will this bridge take me to the lab?

PMID- 16424314
TI  - Society for Integrative and Comparative Biology meeting. Sea slug inks its way to
      safety.

PMID- 16424315
TI  - Society for Integrative and Comparative Biology meeting: Was Lucy's a fighting
      family? Look at her legs.

PMID- 16424316
TI  - Society for Integrative and Comparative Biology meeting. Water launches spores
      like a rocket.

PMID- 16424317
TI  - Society for Integrative and Comparative Biology meeting. Crab, raccoon play tag
      team against turtle.

PMID- 16424323
TI  - Madison and climate change policy.

PMID- 16424324
TI  - Advising on publication.

PMID- 16424325
TI  - HIV prevention in adolescents.

PMID- 16424326
TI  - Planetary science. Risks in space from orbiting debris.

PMID- 16424327
TI  - Microbiology. Weapons of microbial drug resistance abound in soil flora.

PMID- 16424328
TI  - Cell biology. Serving up a plate of chromosomes.

PMID- 16424329
TI  - Applied physics. Helical spin order on the move.

PMID- 16424330
TI  - Astronomy. Nucleosynthesis in binary stars.

PMID- 16424332
TI  - Phospholipid nonwoven electrospun membranes.
AB  - Nonwoven fibrous membranes were formed from electrospinning lecithin solutions in
      a single processing step. As the concentration of lecithin increased, the
      micellar morphology evolved from spherical to cylindrical, and at higher
      concentrations the cylindrical micelles overlapped and entangled in a fashion
      similar to polymers in semi-dilute or concentrated solutions. At concentrations
      above the onset of entanglements of the wormlike micelles, electrospun fibers
      were fabricated with diameters on the order of 1 to 5 micrometers. The
      electrospun phospholipid fibers offer the potential for direct fabrication of
      biologically based, high-surface-area membranes without the use of multiple
      synthetic steps, complicated electrospinning designs, or postprocessing surface
      treatments.

PMID- 16424331
TI  - The impact of structural genomics: expectations and outcomes.
AB  - Structural genomics (SG) projects aim to expand our structural knowledge of
      biological macromolecules while lowering the average costs of structure
      determination. We quantitatively analyzed the novelty, cost, and impact of
      structures solved by SG centers, and we contrast these results with traditional
      structural biology. The first structure identified in a protein family enables
      inference of the fold and of ancient relationships to other proteins; in the year
      ending 31 January 2005, about half of such structures were solved at a SG center
      rather than in a traditional laboratory. Furthermore, the cost of solving a
      structure at the most efficient SG center in the United States has dropped to one
      quarter of the estimated cost of solving a structure by traditional methods.
      However, the efficiency of the top structural biology laboratories-even though
      they work on very challenging structures-is comparable to that of SG centers;
      moreover, traditional structural biology papers are cited significantly more
      often, suggesting greater current impact.

PMID- 16424333
TI  - Covalently bridging gaps in single-walled carbon nanotubes with conducting
      molecules.
AB  - Molecular electronics is often limited by the poorly defined nature of the
      contact between the molecules and the metal surface. We describe a method to wire
      molecules into gaps in single-walled carbon nanotubes (SWNTs). Precise oxidative
      cutting of a SWNT produces carboxylic acid-terminated electrodes separated by
      gaps of </=10 nanometers. These point contacts react with molecules derivatized
      with amines to form molecular bridges held in place by amide linkages. These
      chemical contacts are robust and allow a wide variety of molecules to be tested
      electrically. In addition to testing molecular wires, we show how to install
      functionality in the molecular backbone that allows the conductance of the single
      molecule bridges to switch with pH.

PMID- 16424334
TI  - Real-space observation of helical spin order.
AB  - Helical spin order in magnetic materials has been investigated only in reciprocal
      space. We visualized the helical spin order and dynamics in a metal silicide in
      real space by means of Lorentz electron microscopy. The real space of the helical
      spin order proves to be much richer than that expected from the averaged
      structure; it exhibits a variety of magnetic defects similar to atomic
      dislocations in the crystal lattice. The application of magnetic fields allows us
      to directly observe the deformation processes of the helical spin order
      accompanied by nucleation, movement, and annihilation of the magnetic defects.

PMID- 16424335
TI  - Solvent-free oxidation of primary alcohols to aldehydes using Au-Pd/TiO2
      catalysts.
AB  - The oxidation of alcohols to aldehydes with O2 in place of stoichiometric oxygen
      donors is a crucial process for the synthesis of fine chemicals. However, the
      catalysts that have been identified so far are relatively inactive with primary
      alkyl alcohols. We showed that Au/Pd-TiO2 catalysts give very high turnover
      frequencies (up to 270,000 turnovers per hour) for the oxidation of alcohols,
      including primary alkyl alcohols. The addition of Au to Pd nanocrystals improved
      the overall selectivity and, using scanning transmission electron microscopy
      combined with x-ray photoelectron spectroscopy, we showed that the Au-Pd
      nanocrystals were made up of a Au-rich core with a Pd-rich shell, indicating that
      the Au electronically influences the catalytic properties of Pd.

PMID- 16424336
TI  - Internal rotation and spin conversion of CH3OH in solid para-hydrogen.
AB  - The quantum solid para-hydrogen (p-H2) has recently proven useful in matrix
      isolation spectroscopy. Spectral lines of compounds embedded in this host are
      unusually narrow, and several species have been reported to rotate in p-H2. We
      found that a p-H2 matrix inhibits rotation of isolated methanol (CH3OH) but still
      allows internal rotation about the C-O bond, with splittings of the E/A torsional
      doublet in internal rotation-coupled vibrational modes that are qualitatively
      consistent with those for CH3OH in the gaseous phase. This simplified high
      resolution spectrum further revealed the slow conversion of nuclear spin symmetry
      from species E to species A in the host matrix, offering potential insight into
      nuclear spin conversion in astrophysical sources.

PMID- 16424337
TI  - Formation of glaciers on Mars by atmospheric precipitation at high obliquity.
AB  - Surface conditions on Mars are currently cold and dry, with water ice unstable on
      the surface except near the poles. However, geologically recent glacierlike
      landforms have been identified in the tropics and the midlatitudes of Mars. The
      ice has been proposed to originate from either a subsurface reservoir or the
      atmosphere. We present high-resolution climate simulations performed with a model
      designed to simulate the present-day Mars water cycle but assuming a 45 degrees
      obliquity as experienced by Mars a few million years ago. The model predicts ice
      accumulation in regions where glacier landforms are observed, on the western
      flanks of the great volcanoes and in the eastern Hellas region. This agreement
      points to an atmospheric origin for the ice and reveals how precipitation could
      have formed glaciers on Mars.

PMID- 16424338
TI  - South-seeking magnetotactic bacteria in the Northern Hemisphere.
AB  - Magnetotactic bacteria contain membrane-bound intracellular iron crystals
      (magnetosomes) and respond to magnetic fields. Polar magnetotactic bacteria in
      vertical chemical gradients are thought to respond to high oxygen levels by
      swimming downward into areas with low or no oxygen (toward geomagnetic north in
      the Northern Hemisphere and geomagnetic south in the Southern Hemisphere). We
      identified populations of polar magnetotactic bacteria in the Northern Hemisphere
      that respond to high oxygen levels by swimming toward geomagnetic south, the
      opposite of all previously reported magnetotactic behavior. The percentage of
      magnetotactic bacteria with south polarity in the environment is positively
      correlated with higher redox potential. The coexistence of magnetotactic bacteria
      with opposing polarities in the same redox environment conflicts with current
      models of the adaptive value of magnetotaxis.

PMID- 16424339
TI  - Sampling the antibiotic resistome.
AB  - Microbial resistance to antibiotics currently spans all known classes of natural
      and synthetic compounds. It has not only hindered our treatment of infections but
      also dramatically reshaped drug discovery, yet its origins have not been
      systematically studied. Soil-dwelling bacteria produce and encounter a myriad of
      antibiotics, evolving corresponding sensing and evading strategies. They are a
      reservoir of resistance determinants that can be mobilized into the microbial
      community. Study of this reservoir could provide an early warning system for
      future clinically relevant antibiotic resistance mechanisms.

PMID- 16424340
TI  - Vaccinia virus-induced cell motility requires F11L-mediated inhibition of RhoA
      signaling.
AB  - RhoA signaling plays a critical role in many cellular processes, including cell
      migration. Here we show that the vaccinia F11L protein interacts directly with
      RhoA, inhibiting its signaling by blocking the interaction with its downstream
      effectors Rho-associated kinase (ROCK) and mDia. RNA interference-mediated
      depletion of F11L during infection resulted in an absence of vaccinia-induced
      cell motility and inhibition of viral morphogenesis. Disruption of the RhoA
      binding site in F11L, which resembles that of ROCK, led to an identical
      phenotype. Thus, inhibition of RhoA signaling is required for both vaccinia
      morphogenesis and virus-induced cell motility.

PMID- 16424341
TI  - Core knowledge of geometry in an Amazonian indigene group.
AB  - Does geometry constitute a core set of intuitions present in all humans,
      regardless of their language or schooling? We used two nonverbal tests to probe
      the conceptual primitives of geometry in the Munduruku, an isolated Amazonian
      indigene group. Munduruku children and adults spontaneously made use of basic
      geometric concepts such as points, lines, parallelism, or right angles to detect
      intruders in simple pictures, and they used distance, angle, and sense
      relationships in geometrical maps to locate hidden objects. Our results provide
      evidence for geometrical intuitions in the absence of schooling, experience with
      graphic symbols or maps, or a rich language of geometrical terms.

PMID- 16424342
TI  - A molecular framework for plant regeneration.
AB  - Plants and some animals have a profound capacity to regenerate organs from adult
      tissues. Molecular mechanisms for regeneration have, however, been largely
      unexplored. Here we investigate a local regeneration response in Arabidopsis
      roots. Laser-induced wounding disrupts the flow of auxin-a cell-fate-instructive
      plant hormone-in root tips, and we demonstrate that resulting cell-fate changes
      require the PLETHORA, SHORTROOT, and SCARECROW transcription factors. These
      transcription factors regulate the expression and polar position of PIN auxin
      efflux-facilitating membrane proteins to reconstitute auxin transport in renewed
      root tips. Thus, a regeneration mechanism using embryonic root stem-cell
      patterning factors first responds to and subsequently stabilizes a new hormone
      distribution.

PMID- 16424343
TI  - Chromosomes can congress to the metaphase plate before biorientation.
AB  - The stable propagation of genetic material during cell division depends on the
      congression of chromosomes to the spindle equator before the cell initiates
      anaphase. It is generally assumed that congression requires that chromosomes are
      connected to the opposite poles of the bipolar spindle ("bioriented"). In
      mammalian cells, we found that chromosomes can congress before becoming
      bioriented. By combining the use of reversible chemical inhibitors, live-cell
      light microscopy, and correlative electron microscopy, we found that monooriented
      chromosomes could glide toward the spindle equator alongside kinetochore fibers
      attached to other already bioriented chromosomes. This congression mechanism
      depended on the kinetochore-associated, plus end-directed microtubule motor CENP
      E (kinesin-7).

PMID- 16424344
TI  - Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.
AB  - The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close
      affinities to authentic DNA cytosine methyltransferases. A combined genetic and
      biochemical approach revealed that human DNMT2 did not methylate DNA but instead
      methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid
      transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in
      the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2
      protein restored methylation in vitro to tRNA(Asp) from Dnmt2-deficient strains
      of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was
      dependent on preexisting patterns of modified nucleosides. Indirect sequence
      recognition is also a feature of eukaryotic DNA methyltransferases, which may
      have arisen from a Dnmt2-like RNA methyltransferase.

PMID- 16424345
TI  - Plasminogen activator inhibitor-1 gene: selection of tagging single nucleotide
      polymorphisms and association with coronary heart disease.
AB  - OBJECTIVE: To explore the effect of plasminogen activator inhibitor-1 (PAI-1)
      gene variations on the risk of coronary heart disease (CHD) in Chinese Han
      population. METHODS AND RESULTS: We screened all exons and the promoter region of
      PAI-1 gene in 48 patients and identified 17 polymorphisms. Five tagging single
      nucleotide polymorphisms were selected and genotyped in 816 patients with CHD and
      937 controls. In the total sample, no main effects of the loci or haplotypes
      reached statistical significance after adjusting environmental covariates.
      However, a strongly significant gene-smoking interaction was observed. Among
      nonsmokers, 2 polymorphisms located at promoter region (rs2227631 and rs1799889)
      showed significant association with CHD. The cases had higher frequency of
      rs2227631 A allele and rs1799889 4G allele than the controls (0.42 versus 0.33,
      P=0.001; 0.60 versus 0.52, P=0.002). Haplotype analyses confirmed the effects of
      the PAI-1 gene-smoking interaction on CHD risk. Compared with the most common
      haplotype G-5G-A-A-T (35.1%), the haplotype A-4G-A-A-C (32.7%) significantly
      increased the risk of CHD with adjusted odds ratio of 1.51 (95% CI, 1.12 to 2.05;
      P=0.008) in nonsmokers. CONCLUSIONS: This study identified a significant
      interaction between PAI-1 gene and smoking status. Both single locus and
      haplotype analyses indicated that rs2227631 A allele and rs1799889 4G allele
      increased the risk of CHD among nonsmokers in Chinese.

PMID- 16424346
TI  - A possible association between coronary plaque instability and complex plaques in
      abdominal aorta.
AB  - OBJECTIVE: Coronary plaque instability causes myocardial infarction (MI).
      Angiographic lesions with such instability are complex lesions. Complex carotid
      plaques were reported to be prevalent in unstable angina. We investigated
      associations between coronary plaque instability, such as MI and angiographic
      complex coronary lesions, and aortic plaques. METHODS AND RESULTS: Aortic MRI was
      performed in 146 patients undergoing coronary angiography, of whom 108 had
      coronary artery disease (CAD) and 44 also had MI. Prevalence of plaques in
      thoracic and abdominal aortas was higher in patients with than without CAD (73%
      and 94% versus 32% and 79%), but it was similar in CAD patients with and without
      MI. Notably, complex plaques in abdominal aorta were more prevalent in CAD
      patients with than without MI (36% versus 14%; P<0.025). In multivariate
      analysis, abdominal complex plaques were associated with MI (odds ratio [OR],
      4.5; 95% CI, 1.5 to 13.8). Among patients without MI, thoracic and abdominal
      complex plaques were more prevalent in patients with than without complex
      coronary lesions (22% and 33% versus 2% and 7%; P<0.05). Abdominal complex
      plaques were also associated with complex coronary lesions (OR, 9.8; 95% CI, 1.1
      to 85.9). CONCLUSIONS: Complex plaques in abdominal aorta were associated with MI
      and complex coronary lesions, suggesting a link between coronary and aortic
      plaque instability.

PMID- 16424347
TI  - Eplerenone with valsartan effectively reduces atherosclerotic lesion by
      attenuation of oxidative stress and inflammation.
AB  - OBJECTIVE: Angiotensin II contributes to atherogenesis, mainly through oxidative
      stress and inflammation. Recent data suggest that aldosterone is implicated in
      some effects of angiotensin II. We hypothesized that aldosterone could directly
      contribute to oxidative stress and atherosclerotic lesion formation. METHODS AND
      RESULTS: Male apolipoprotein E-deficient mice 6 weeks of age were placed on a
      normal diet or 1.25% high-cholesterol diet. After 6 weeks of the high-cholesterol
      diet, a marked increase in atherosclerotic lesion formation was observed in the
      aorta, accompanied by significant elevation of plasma cholesterol level.
      Production of superoxide anion and expression of NAD(P)H oxidase subunit p47phox,
      tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in the aorta
      were increased with the high-cholesterol diet. Eplerenone (1.67 g/kg in high
      cholesterol diet) did not affect blood pressure or plasma cholesterol but
      decreased the atherosclerotic area by nearly 70% (P<0.05), associated with
      attenuation of oxidative stress and inflammatory response. Valsartan (0.5 mg/kg
      per day) also decreased the atherosclerotic lesion, whereas coadministration of
      valsartan and eplerenone further decreased it. Moreover, aldosterone (0.1
      micromol/L) enhanced NADPH oxidase activity in cultured vascular smooth muscle
      cells. CONCLUSIONS: These results suggest that aldosterone may play a critical
      role in atherogenesis subsequent to oxidative stress in part independent of
      angiotensin II-mediated signaling, and that eplerenone could prevent
      atherosclerosis by attenuating oxidative stress and inflammation.

PMID- 16424348
TI  - PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell
      proliferation, and reduces neointima formation after balloon injury in rats.
AB  - OBJECTIVE: There is still debate as to whether antiatherosclerotic effect of
      PPARgamma ligands is dependant on PPARgamma gene itself or some other pathway.
      METHODS AND RESULTS: To investigate the effect of PPARgamma gene modulation on
      neointima formation after balloon injury, we delivered adenoviral vectors
      expressing the wild-type (WT) dominant negative (DN) PPARgamma, or a control gene
      (beta-galactosidase [BG]) into carotid artery after balloon injury in
      rosiglitazone (a PPARgamma ligand)-treated (R+) (3 mg/kg/d) and nontreated (R-)
      rats. Two weeks after gene delivery, in both R+ and R- animals, the PPARgamma-WT
      gene transfer showed a significantly lower intima-media ratio (IMR) than control
      group. Moreover, the delivery of a PPARgamma-DN form showed the highest IMR (in
      R+WT, 0.51+/-0.15; R+BG, 0.89+/-0.14; R+DN, 1.20+/-0.18, P<0.05 and in R-WT,
      0.91+/-0.21; R-BG, 1.44+/-0.23; R-DN, 1.74+/-0.29, P<0.05). Proliferation and
      migration showed same result pattern as IMR. In addition, apoptotic indices were
      significantly higher in the PPARgamma-WT gene transferred group than in the
      PPARgamma-DN group. CONCLUSIONS: In vivo transfer of the PPARgamma-WT gene was
      found to inhibit smooth muscle proliferation, sustain apoptosis, and reduce
      neointima formation after balloon injury irrespective of rosiglitazone treatment.
      These results indicate that PPARgamma overexpression itself has a protective role
      against restenosis after balloon injury.

PMID- 16424349
TI  - Influence of folate on arterial permeability and stiffness in the absence or
      presence of hyperhomocysteinemia.
AB  - OBJECTIVE: Elevated plasma total homocysteine (tHcy) is associated with risk for
      cardiovascular disease. A common cause of mild hyperhomocysteinemia (HHcy) is
      folate deficiency. We sought to determine whether folate deficiency per se
      increases arterial permeability (quantitative fluorescence microscopy) and
      stiffness (vessel elastigraph), and whether the effects of folate deficiency are
      more severe in the presence of mild HHcy. METHODS AND RESULTS: Heterozygous
      cystathionine beta-synthase (CBS)-deficient mice (CBS(+/-)) and their wild-type
      littermates (CBS(+/+)) were fed chow containing either standard (Con) or
      relatively low amounts of folate (LF) for 18+/-3 weeks. Liver folate (microg
      folate/g liver) and tHcy (microM), respectively, were 12+/-1 and 8+/-1 in
      CBS(+/+) Con mice (n=12), and 8+/-1 and 8+/-1 in CBS(+/+) LF animals (n=5).
      Carotid arterial permeability was &38% greater (P<0.05) in CBS(+/+) LF versus Con
      mice, but vascular stiffening was unaltered. Liver folate and tHcy, respectively,
      were 13+/-1 and 11+/-1 in CBS(+/-) Con mice (n=16), and 8+/-1 and 16+/-3 in
      CBS(+/-) LF animals (n=6). Carotid arterial dextran accumulation was &31%
      greater, and maximal strain in aortae was &20% lower (both P<0.05) in CBS(+/-) LF
      versus Con mice. CONCLUSIONS: Taken together, low folate (P<0.05) combined with
      mild HHcy (P<0.05) in CBS(+/-) mice produced more arterial dysfunction compared
      with low folate alone (ie, CBS(+/+) mice). These findings may be particularly
      relevant to elderly individuals because tHcy and deficiencies of folate
      metabolism increase with age.

PMID- 16424350
TI  - Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology
      and therapeutics.
AB  - The ability of oxyhemoglobin to inhibit nitric oxide (NO)-dependent activation of
      soluble guanylate cyclase and vasodilation provided some of the earliest
      experimental evidence that NO was the endothelium-derived relaxing factor (EDRF).
      The chemical behavior of this dioxygenation reaction, producing nearly diffusion
      limited and irreversible NO scavenging, presents a major paradox in vascular
      biology: The proximity of large amounts of oxyhemoglobin (10 mmol/L) to the
      endothelium should severely limit paracrine NO diffusion from endothelium to
      smooth muscle. However, several physical factors are now known to mitigate NO
      scavenging by red blood cell encapsulated hemoglobin. These include diffusional
      boundaries around the erythrocyte and a red blood cell free zone along the
      endothelium in laminar flowing blood, which reduce reaction rates between NO and
      red cell hemoglobin by 100- to 600-fold. Beyond these mechanisms that reduce NO
      scavenging by hemoglobin within the red cell, 2 additional mechanisms have been
      proposed suggesting that NO can be stored in the red blood cell either as nitrite
      or as an S-nitrosothiol (S-nitroso-hemoglobin). The latter controversial
      hypothesis contends that NO is stabilized, transported, and delivered by intra
      molecular NO group transfers between the heme iron and beta-93 cysteine to form S
      nitroso-hemoglobin (SNO-Hb), followed by hypoxia-dependent delivery of the S
      nitrosothiol in a process that links regional oxygen deficits with S-nitrosothiol
      mediated vasodilation. Although this model has generated a field of research
      examining the potential endocrine properties of intravascular NO molecules,
      including S-nitrosothiols, nitrite, and nitrated lipids, a number of mechanistic
      elements of the theory have been challenged. Recent data from several groups
      suggest that the nitrite anion (NO2-) may represent the major intravascular NO
      storage molecule whose transduction to NO is made possible through an
      allosterically controlled nitrite reductase reaction with the heme moiety of
      hemoglobin. As subsequently understood, the hypoxic generation of NO from nitrite
      is likely to prove important in many aspects of physiology, pathophysiology, and
      therapeutics.

PMID- 16424352
TI  - Modulation of hepatic inflammatory risk markers of cardiovascular diseases by
      PPAR-alpha activators: clinical and experimental evidence.
AB  - Atherosclerosis is a long-term chronic inflammatory disease associated with
      increased concentrations of inflammatory hepatic markers, such as CRP and
      fibrinogen, and of peripheral origin, such as tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-6. Peroxisome proliferator-activated receptor (PPAR-)-alpha
      is a ligand-activated transcription factor that regulates expression of key genes
      involved in lipid homeostasis and modulates the inflammatory response both in the
      vascular wall and the liver. PPAR-alpha is activated by natural ligands, such as
      fatty acids, as well as the lipid-lowering fibrates. PPAR-alpha agonists impact
      on different steps of atherogenesis: (1) early markers of atherosclerosis, such
      as vascular wall reactivity, are improved, (2) however, reduced expression of
      adhesion molecules on the surface of endothelial cells, accompanied by decreased
      levels of inflammatory cytokines, such as TNF-alpha, IL-1, and IL-6, leads to a
      decreased leukocyte recruitment into the arterial wall; (3) in later stages of
      the atherosclerotic process, PPAR-alpha agonists may promote plaque stabilization
      and reduce cardiovascular events, via effects on metalloproteinases, such as
      MMP9. Moreover, PPAR-alpha activation by fibrates also impairs proinflammatory
      cytokine-signaling pathways in the liver resulting in the modulation of the acute
      phase response reaction via mechanisms independent of changes in lipoprotein
      levels. Effective coronary artery disease (CAD) prevention requires the use of
      agents that act beyond low-density lipoprotein cholesterol-lowering. PPAR-alpha
      agonists appear to comprehensively address some of the abnormalities of the most
      common clinical phenotypes of the high CAD risk patient of the 21st century such
      as in the metabolic syndrome and type 2 diabetes: low high-density lipoprotein
      cholesterol, high triglycerides, small, dense low-density lipoprotein, and a
      proinflammatory, procoagulant state.

PMID- 16424351
TI  - Enhanced T-cell expression of RANK ligand in acute coronary syndrome: possible
      role in plaque destabilization.
AB  - OBJECTIVE: Based on its role in inflammation and matrix degradation, we
      hypothesized a role for osteoprotegerin (OPG), RANK, and RANK ligand (RANKL) in
      coronary artery disease. METHODS AND RESULTS: We examined the expression of
      various members of the OPG/RANKL/RANK axis in patients with stable and unstable
      angina and in the atherosclerotic lesions of apolipoprotein E-deficient (apoE(-/
      )) mice. Our findings were: (1) Serum levels of OPG were raised in patients with
      unstable angina (n=40), but not in those with stable angina (n=40), comparing
      controls (n=20); (2) mRNA levels of RANKL were increased in T-cells in unstable
      angina patients accompanied by increased expression of RANK in monocytes; (3)
      strong immunostaining of OPG/RANKL/RANK was seen within thrombus material
      obtained at the site of plaque rupture during acute myocardial infarction; (4)
      OPG/RANKL/RANK was expressed in the atherosclerotic plaques of apoE(-/-) mice,
      with RANKL located specifically to the plaques; and (5) RANKL enhanced the
      release of monocyte chemoattractant peptide-1 in mononuclear cells from unstable
      angina patients, and promoted matrix metalloproteinase (MMP) activity in vascular
      smooth muscle cells. CONCLUSIONS: We show enhanced expression of the
      OPG/RANKL/RANK system both in clinical and experimental atherosclerosis, with
      enhanced T-cell expression of RANKL as an important feature of unstable disease.

PMID- 16424354
TI  - Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and
      possibly increased response to statin therapy.
AB  - OBJECTIVE: The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene encodes
      a proprotein convertase that causes degradation of cell surface low-density
      lipoprotein receptors (LDLRs). Mutations in the PCSK9 gene that disrupt the
      normal function of PCSK9 could therefore result in increased number of LDLRs and
      hypocholesterolemia. Also, the cholesterol-lowering effect of statins could be
      increased in subjects carrying mutations in the PCSK9 gene. METHODS AND RESULTS:
      We have screened 38 unrelated hypocholesterolemic subjects as well as 25
      unrelated familial hypercholesterolemia (FH) heterozygotes who responded
      particularly well to statin therapy for mutations in the 12 exons of the PCSK9
      gene by DNA sequencing. Six of the 38 (15.8%) hypocholesterolemic subjects were
      heterozygous for 1 of the 3 mutations R46L, G106R, or R237W in the PCSK9 gene. In
      the group of 25 FH heterozygotes who responded particularly well to statin
      therapy, 3 (8.8%) were heterozygous for mutations R46L or N157K in the PCSK9
      gene. None of 441 hypercholesterolemic subjects without mutations in the LDLR
      gene or in the apolipoprotein B-100 gene possessed any of the 4 mutations.
      CONCLUSIONS: The 4 missense mutations R46L, G106R, N157K, and R237W are
      associated with hypocholesterolemia and possibly increased response to statin
      therapy.

PMID- 16424353
TI  - Vascular responses to alpha1-adrenergic receptors in small rat mesenteric
      arteries depend on mitochondrial reactive oxygen species.
AB  - BACKGROUND: Agonists of G-protein-coupled receptors (eg, adrenoceptors and
      angiotensin receptors) signal, at least in part, through matrix
      metalloproteinases (such as matrix metalloproteinase [MMP]-7) that transactivate
      the epidermal growth factor receptor (EGFR). Focusing on adrenoceptors, we
      examined whether the MMP-dependent signaling pathway depends on reactive oxygen
      species (ROS). METHODS AND RESULTS: In isolated rat mesenteric arteries,
      selective stimulation of alpha1-adrenoceptors with phenylephrine induced MMP
      transactivation of the EGFR, mitochondrial ROS production (detected by
      MitoTrackerRed-CM-H2XRos-fluorescence and dihydroethidium-fluorescence and high
      performance liquid chromatography [HPLC]/MS assay) and vasoconstriction.
      Inhibition of the synthesis of either MMP-7 or EGFR with anti-sense or siRNA
      oligonucleotides, respectively, decreased mitochondrial ROS production in
      response to phenylephrine. Targeted mitochondrial ROS scavenging with
      MitoTrackerRed-CM-H2XRos inhibited adrenergic vasoconstriction. Adrenoceptor
      induced ROS increased mitochondrial membrane potential (Deltapsim), which was
      prevented by blockers of MMPs (GM6001, doxycycline), EGFR (AG1478), or complex I,
      all of which also prevented ROS production as well as vasoconstriction.
      CONCLUSIONS: Production of mitochondrial ROS is a new event in the pathway by
      which vasoactive agonists that induce MMP transactivation of the EGFR modulate
      vascular tone. Moreover, our findings suggest a connection between agonist
      induced activity of MMPs, the promotion of oxidative stress, enhanced vascular
      tone, and hypertrophy, which are all implicated in the development and
      progression of vascular disease.

PMID- 16424355
TI  - Assessment of hemostatic risk factors in predicting arterial thrombotic events.

PMID- 16424356
TI  - CD8+ T-cell subpopulations in human abdominal aortic aneurysm lesion.

PMID- 16424357
TI  - Vitamin E limits AAA.

PMID- 16424358
TI  - Leukocytosis, vascular disease, and adenine nucleotide metabolism.

PMID- 16424359
TI  - Adiponectin: vascular protection from the fat?

PMID- 16424360
TI  - Arginine/arginase NO NO NO.

PMID- 16424361
TI  - Leukocyte and endothelial angiotensin II type 1 receptors and microvascular
      thrombotic and inflammatory responses to hypercholesterolemia.

PMID- 16424362
TI  - Quantification of abdominal aortic calcification on CT.

PMID- 16424363
TI  - Insulin resistance and increased intimal medial thickness in glucose tolerant
      offspring of type 2 diabetic subjects carrying the D298D genotype of endothelial
      nitric oxide synthase.

PMID- 16424364
TI  - Salivary lysozyme and prevalent coronary heart disease: possible effects of oral
      health on endothelial dysfunction.

PMID- 16424366
TI  - Cellular senescence impairs circadian expression of clock genes in vitro and in
      vivo.
AB  - Circadian rhythms are regulated by a set of clock genes that form transcriptional
      feedback loops and generate circadian oscillation with a 24-hour cycle. Aging
      alters a broad spectrum of physiological, endocrine, and behavioral rhythms.
      Although recent evidence suggests that cellular aging contributes to various age
      associated diseases, its effects on the circadian rhythms have not been examined.
      We report here that cellular senescence impairs circadian rhythmicity both in
      vitro and in vivo. Circadian expression of clock genes in serum-stimulated
      senescent cells was significantly weaker compared with that in young cells.
      Introduction of telomerase completely prevented this reduction of clock gene
      expression associated with senescence. Stimulation by serum activated the cAMP
      response element-binding protein, but the activation of this signaling pathway
      was significantly weaker in senescent cells. Treatment with activators of this
      pathway effectively restored the impaired clock gene expression of senescent
      cells. When young cells were implanted into young mice or old mice, the implanted
      cells were effectively entrained by the circadian rhythm of the recipients. In
      contrast, the entrainment of implanted senescent cells was markedly impaired.
      These results suggest that senescence decreases the ability of cells to transmit
      circadian signals to their clocks and that regulation of clock gene expression
      may be a novel strategy for the treatment of age-associated impairment of
      circadian rhythmicity.

PMID- 16424365
TI  - High basal protein kinase A-dependent phosphorylation drives rhythmic internal
      Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells.
AB  - Local, rhythmic, subsarcolemmal Ca2+ releases (LCRs) from the sarcoplasmic
      reticulum (SR) during diastolic depolarization in sinoatrial nodal cells (SANC)
      occur even in the basal state and activate an inward Na(+)-Ca2+ exchanger current
      that affects spontaneous beating. Why SANC can generate spontaneous LCRs under
      basal conditions, whereas ventricular cells cannot, has not previously been
      explained. Here we show that a high basal cAMP level of isolated rabbit SANC and
      its attendant increase in protein kinase A (PKA)-dependent phosphorylation are
      obligatory for the occurrence of spontaneous, basal LCRs and for spontaneous
      beating. Gradations in basal PKA activity, indexed by gradations in phospholamban
      phosphorylation effected by a specific PKA inhibitory peptide were highly
      correlated with concomitant gradations in LCR spatiotemporal synchronization and
      phase, as well as beating rate. Higher levels of basal PKA inhibition abolish
      LCRs and spontaneous beating ceases. Stimulation of beta-adrenergic receptors
      extends the range of PKA-dependent control of LCRs and beating rate beyond that
      in the basal state. The link between SR Ca2+ cycling and beating rate is also
      present in vivo, as the regulation of beating rate by local beta-adrenergic
      receptor stimulation of the sinoatrial node in intact dogs is markedly blunted
      when SR Ca2+ cycling is disrupted by ryanodine. Thus, PKA-dependent
      phosphorylation of proteins that regulate cell Ca2+ balance and spontaneous SR
      Ca2+ cycling, ie, phospholamban and L-type Ca2+ channels (and likely others not
      measured in this study), controls the phase and size of LCRs and the resultant
      Na(+)-Ca2+ exchanger current and is crucial for both basal and reserve cardiac
      pacemaker function.

PMID- 16424367
TI  - Neurogenic mechanisms contribute to hypertension in mice with disruption of the K
      Cl cotransporter KCC3.
AB  - The neurodegenerative disorder Andermann syndrome is caused by mutations of the K
      Cl cotransporter KCC3. Mice with a targeted disruption of the corresponding gene,
      Slc12a6, reproduce neurodegeneration of the peripheral and central nervous system
      (CNS) and display arterial hypertension. Kcc3 is expressed in numerous tissues,
      including the CNS and vascular smooth muscle cells. As the intracellular chloride
      concentration may influence myogenic tone and hence blood pressure, we measured
      the chloride concentration in vascular smooth muscle cells. It was indeed
      increased in superficial brain arteries and saphenous arteries of Kcc3(-/-) mice.
      Isolated saphenous arteries and their third-order branches, however, reacted
      indistinguishably to changes in intravascular pressure, stimulation of alpha1
      adrenoreceptors, exogenous nitric oxide, or blockade of calcium-activated
      chloride channels. Likewise, the responses to alpha1-adrenergic stimulation or
      exogenous nitric oxide in vivo were identical in both genotypes. These results
      argue against a major vascular-intrinsic component of arterial hypertension in
      Kcc3(-/-) mice. In contrast, either alpha1-adrenergic blockade or inhibition of
      ganglionic transmission abolished the difference in arterial blood pressure
      between both genotypes. This demonstrates a neurogenic component in the
      maintenance of this phenotype, which is further supported by an increase of
      urinary norepinephrine and epinephrine excretion in Kcc3(-/-) mice. Our data
      indicate that local control of myogenic tone does not require KCC3 and that
      hypertension in Kcc3(-/-) mice depends on an elevated sympathetic tone.

PMID- 16424368
TI  - Interleukin 12 induces T-cell recruitment into the atherosclerotic plaque.
AB  - CD4 T cells, through the release of cytokines as well as direct effector
      functions, have been implicated in promoting inflammation of the atherosclerotic
      plaque. Plaque-infiltrating CD4 T cells include a specialized subset of
      (CD4+)CD28- T cells that express a unique profile of regulatory receptors and are
      responsive to novel microenvironmental cues. Here we report that (CD4+)CD28- T
      cells, either isolated from the plaque tissue or from the blood of patients with
      acute coronary syndrome (ACS), spontaneously express interleukin (IL)-12
      receptors, even in the absence of antigenic stimulation. (CD4+)CD28- IL-12R+
      cells responded to IL-12 stimulation with the upregulation of the chemokine
      receptor CCR5 and the C-type lectin receptor CD161, both implicated in regulating
      tissue homing of effector T cells. IL-12 treatment of (CD4+)CD28- T cells
      enhanced their chemotaxis and transendothelial migration toward the chemokine
      CCL5. In vivo relevance for the role of IL-12 in regulating the recruitment of
      (CD4+)CD28- T cells into the atheroma was examined in human atheroma-SCID mouse
      chimeras. Exposure of nonstimulated (CD4+)CD28- T cells to IL-12 was sufficient
      to amplify T-cell accumulation within the inflamed plaque, and coadministration
      of anti-CCR5 antibodies blocked T-cell recruitment into the plaque. Thus,
      (CD4+)CD28- T cells functionally resemble NK cells, which have proinflammatory
      activity even in the unprimed state and respond to any IL-12-inducing host
      infection with a shift in tissue trafficking and accrual in inflammatory lesions.

PMID- 16424369
TI  - A novel prostaglandin E receptor 4-associated protein participates in
      antiinflammatory signaling.
AB  - Prostaglandin E2 exerts an antiinflammatory action by ligation of the
      heptahelical receptor EP4 in human macrophages. Because the mechanism by which
      EP4 receptor stimulation suppresses inflammatory activation in macrophages
      remains undefined, we sought interactors with the carboxyl-terminal cytoplasmic
      domain of the EP4 receptor. Yeast 2-hybrid screening of the human bone marrow
      cDNA library with the EP4 receptor as a bait identified a cDNA clone encoding a
      669-amino acid protein, designated here as EP4 receptor-associated protein
      (EPRAP), which contains 8 ankyrin motifs that might recruit other signaling
      molecules. EPRAP bound to the full-length EP4 receptor in HEK293 cells
      cotransfected with V5-tagged EPRAP and FLAG-tagged EP4 receptor cDNA, as anti
      FLAG antibody coimmunoprecipitated EPRAP with the EP4 receptor from the lysates
      of cotransfected cells. Human macrophages derived from peripheral blood monocytes
      expressed an approximately 70-kDa protein detected by Western blotting with a
      polyclonal anti-EPRAP antibody. Fluorescence immunohistochemistry colocalized
      EPRAP with the EP4 receptor in human atheromata. Interference with EPRAP function
      by small interference RNA limited prostaglandin E2-mediated suppression of
      chemokine expression in macrophages activated with lipopolysaccharide and tumor
      necrosis factor alpha. In conclusion, the antiinflammatory action of
      prostaglandin E2 in macrophages involves EPRAP that associates directly with the
      cytoplasmic tail of EP4 receptor.

PMID- 16424370
TI  - SERPINA3 polymorphism is not associated with primary intracerebral hemorrhage in
      a Polish population.
AB  - BACKGROUND AND PURPOSE: Genetic factors involved in the pathogenesis of primary
      intracerebral hemorrhage (PICH) remain unknown. One of the candidate genes is
      SERPINA3. Results of a Spanish study suggested that TT genotype of the A/T
      SERPINA3 polymorphism in the signal peptide sequence was a risk factor for PICH
      in normotensive subjects. The aim of the present study was to investigate whether
      SERPINA3 A/T polymorphism is associated with PICH in a Polish population.
      METHODS: We analyzed 95 PICH patients and 190 unrelated healthy controls matched
      for age and sex. A/T polymorphism of the SERPINA3 gene was investigated using
      polymerase chain reaction restriction fragment length polymorphism method.
      RESULTS: The distribution of SERPINA3 genotypes was similar among PICH patients
      (AA 27.4%; AT 46.3%; TT 26.3%) and controls (AA 23.7%; AT 50.5%; TT 25.8%; P=NS).
      There were also no significant differences in genotype distribution when
      analyzing separately hypertensive and normotensive PICH patients as well as
      patients with lobar and deeply located hemorrhage. CONCLUSIONS: We failed to find
      an association between SERPINA3 A/T polymorphism and PICH in a Polish population.

PMID- 16424371
TI  - Seropositivity to Chlamydia pneumoniae is associated with risk of first ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Serologic evidence of infection with Chlamydia pneumoniae
      has been associated with cardiovascular disease, but its relationship with stroke
      risk remains uncertain. The objective of this study is to determine whether
      serological evidence of C pneumoniae infection is associated with risk of
      ischemic stroke. METHODS: A population-based case-control study was performed in
      an urban, multiethnic population. Cases (n=246) had first ischemic stroke, and
      controls (n=474) matched for age, sex, and race-ethnicity were derived through
      random-digit dialing. Titers of C pneumoniae-specific IgG and IgA antibodies were
      measured using microimmunofluorescence, and positive titers were prospectively
      defined. Conditional logistic regression was used to calculate odds ratios (ORs)
      and 95% CIs adjusting for medical, behavioral, and socioeconomic factors.
      RESULTS: Mean age among cases was 72.3+/-9.7 years; 50.8% were women. Elevated C
      pneumoniae IgA titers were associated with increased risk of ischemic stroke
      after adjusting for hypertension, diabetes mellitus, current cigarette use,
      atrial fibrillation, and levels of high-density lipoprotein and low-density
      lipoprotein (adjusted OR, 1.5; 95% CI, 1.0 to 2.2). Elevated IgG titers were not
      associated with stroke risk (adjusted OR, 1.2; 95% CI, 0.8 to 1.8). There was a
      trend toward an association of elevated IgA titers with atherosclerotic and
      lacunar stroke but less so cardioembolic or cryptogenic subtypes. CONCLUSIONS:
      Serologic evidence of C pneumoniae infection is associated with ischemic stroke
      risk. IgA titers may be a better marker of risk than IgG. This association is
      independent of other stroke risk factors and is present for atherosclerotic,
      lacunar, and cardioembolic subtypes. Further studies of the effect of C
      pneumoniae on stroke risk are warranted.

PMID- 16424372
TI  - Characteristics of an "ill-defined" diagnosis for stroke: opportunities for
      improvement.
AB  - BACKGROUND AND PURPOSE: Rapid and accurate evaluation of stroke subtypes is
      crucial for optimal treatment and outcomes. This study assessed factors
      associated with the likelihood of an "ill-defined" diagnosis for stroke
      hospitalizations. METHODS: We examined all hospital claims for stroke among
      Medicare beneficiaries aged > or =65 years in 2000. Stroke subtypes included
      hemorrhagic (International Classification of Diseases, Ninth Revision, Clinical
      Modification codes 430 to 432), ischemic (433 to 434), ill-defined (436 to 437),
      and late effects of cerebrovascular disease (438). RESULTS: Among 445 452
      hospital claims for stroke, 65.3% were ischemic, 20.9% were ill defined, 11.9%
      were hemorrhagic, and 1.9% were late effects of cerebrovascular disease. After
      controlling for age, women (odds ratio [OR],1.30; 95% CI, 1.28 to 1.32), blacks
      (OR, 1.31; 95% CI, 1.28 to 1.33), and Hispanics (OR, 1.27; 95% CI, 1.20 to 1.34)
      were more likely to receive a discharge diagnosis of ill defined compared with
      men and whites, respectively. Differences in age, sex, emergency room
      presentation, and evidence of diagnostic procedures accounted for some but not
      all racial disparities. In 14 states, ill-defined strokes constituted > or =25%
      of all stroke diagnoses. CONCLUSIONS: The high proportion of stroke patients who
      receive an ill-defined diagnosis on discharge suggests a continued need for
      improvements in early response and prompt evaluation of strokes. Findings of
      geographic, gender, and racial disparities in ill-defined stroke diagnosis
      warrant further investigation. Reimbursement practices and public health efforts
      that promote hospital stroke policies are critical to improve disease reporting
      as well as clinical outcomes.

PMID- 16424374
TI  - Internal and cortical border-zone infarction: clinical and diffusion-weighted
      imaging features.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of internal border-zone (IBZ) and
      cortical border-zone (CBZ) infarcts is unclear. Both types of infarct have been
      combined into a single group in most previous reports, which has produced
      conflicting results. We hypothesized that different pathogenic mechanisms
      underlie IBZ and CBZ infarcts. METHODS: We reviewed 946 consecutive patients with
      ischemic stroke within the middle cerebral artery territory. IBZ and CBZ infarcts
      were selected based on diffusion-weighted imaging templates to identify vascular
      territories. Baseline patient characteristics, clinical courses, and
      neuroradiological features were compared between patients with IBZ and CBZ
      infarcts. RESULTS: We identified 45 IBZ and 75 CBZ infarct patients. Compared
      with the CBZ infarct patients, IBZ infarct patients had a higher degree of
      stenosis or occlusion in either the middle cerebral or internal carotid artery
      (P=0.008) and exhibited a rosary-like pattern of infarction more frequently
      (P<0.001). In contrast, concomitant small cortical infarcts were observed more
      frequently in CBZ infarct patients (P<0.001). Clinical deterioration during the
      first 7 days of admission and poor outcome after 3 months after stroke was more
      prevalent in IBZ infarct patients than in CBZ infarct patients (P=0.002 and
      P=0.003, respectively). CONCLUSIONS: IBZ infarcts are caused mainly by
      hemodynamic compromise, whereas embolic pathogenesis appears to contribute
      greatly to the genesis of CBZ infarcts. Patients with IBZ infarcts showed poor
      early and late clinical courses. Our findings suggest that different therapeutic
      approaches may be required to prevent early clinical deterioration in patients
      with different types of border-zone infarcts.

PMID- 16424373
TI  - A pilot study of a new thrombolytic agent for acute ischemic stroke in Taiwan
      within a five-hour window.
AB  - BACKGROUND AND PURPOSE: This study was the first clinical trial in Taiwan of a
      new thrombolytic agent human tissue urokinase type plasminogen activator (HTUPA)
      in patients with acute ischemic stroke. METHODS: Patients were treated with a
      single bolus intravenous HTUPA under an open-label dose escalation design within
      5 hours after symptom onset. Safety outcomes were assessed by symptomatic and
      asymptomatic intracerebral hemorrhage (ICH) as well as other bleeding episodes.
      Preliminary efficacy was measured by National Institutes of Health Stroke Scale
      (NIHSS). RESULTS: Three doses of HTUPA (0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg)
      were administered to 33 patients, with the majority of patients (n=29) receiving
      0.3 mg/kg. Two cases of fatal ICH occurred: 1 in the patient who received 0.4
      mg/kg and the other in the 0.3 mg/kg group. Asymptomatic ICH occurred in 6
      patients. Other treatment-related serious adverse events were ecchymosis,
      hematuria, and upper gastrointestinal bleeding, which were completely recovered.
      At day 90, in patients treated with 0.3 mg/kg within a 0- to 5-hour window, 34%
      reached NIHSS scores 0 to 1, whereas of those treated within 0 to 3 hours, 86%
      reached this score. CONCLUSIONS: Intravenous HTUPA, given at 0.3 mg/kg as a bolus
      injection within 5 hours after symptom onset, had an acceptable safety and
      efficacious profile in patients with acute ischemic stroke.

PMID- 16424375
TI  - Chlamydia pneumoniae, stroke, and serological associations: anything learned from
      the atherosclerosis-cardiovascular literature or do we have to start over again?

PMID- 16424376
TI  - Stroke onset time using sodium MRI in rat focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Thrombolytic therapy with intravenous tPA must be
      administered within 3 hours after stroke onset. However, stroke onset time cannot
      be established in 20% to 45% of potential patients. We propose that the rate of
      increase of the brain concentration of sodium ([Na+]br) after stroke, monitored
      using sodium MRI in a rat model of cortical ischemia, is linear in each
      individual animal, can locate the ischemic region, and can be used to estimate
      onset time. METHODS: After induction of focal cortical ischemia in rats under
      isoflurane anesthesia, [Na+]br time course maps were acquired continuously on a 3
      T whole body scanner from 2 to 7 hours after occlusion followed by T2-weighted
      proton images. Microtubule-associated protein-2 immunostained brain sections were
      used to verify the location of the infarct. RESULTS: The ischemic region
      identified with microtubule-associated protein-2 corresponded to the region of
      maximum [Na+]br increase (P<0.001; n=5), and all of the animals demonstrated high
      linearity. [Na+]br increased at a mean rate of 25+/-4.7%/h in ischemic tissue
      (P=0.013) but not in normal cortex (1.0+/-1.1%/h; P=0.42). The mean onset time
      error was 1+/-4 minutes (n=4). CONCLUSIONS: These results of sodium MRI show that
      the region of maximum [Na+]br increase corresponds to the ischemic region.
      Although [Na+]br increases at a different rate in each animal, the increase is
      linear, and, therefore, onset time can be estimated. These findings suggest that
      this method can be used as a ticking clock to estimate time elapsed after
      vascular occlusion.

PMID- 16424377
TI  - Greater incidence of both fatal and nonfatal strokes in disadvantaged areas: the
      Northeast Melbourne Stroke Incidence Study.
AB  - BACKGROUND AND PURPOSE: Greater stroke mortality has been reported among lower
      socioeconomic groups. We aimed to determine whether fatal, nonfatal, and overall
      stroke incidence varied by socioeconomic status. METHODS: All suspected strokes
      occurring in 22 postcodes (population of 306,631) of Melbourne, Australia, during
      a 24-month period between 1997 and 1999 were found and assessed. Multiple
      overlapping sources were used to ascertain cases with standard clinical
      definitions for stroke. Socioeconomic disadvantage was assigned in 4 bands from
      least to greatest using an area-based measure developed by the Australian Bureau
      of Statistics. RESULTS: Overall stroke incidence (number per 100,000 population
      per year), adjusted to the European population 45 to 84 years of age, increased
      with increasing socioeconomic disadvantage: 200 (95% CI, 173 to 228); 251 (95%
      CI, 220 to 282); 309 (95% CI, 274 to 343); and 366 (95% CI, 329 to 403; chi2 for
      ranks; P<0.0001). Similar incidence patterns were observed for both fatal and
      nonfatal stroke. Nonfatal stroke contributed most to this incidence pattern: 146
      (95% CI, 122 to 169); 181 (95% CI, 155 to 207); 223 (95% CI, 194 to 252); and 280
      (95% CI, 247 to 313; chi2 for ranks; P<0.0001). CONCLUSIONS: In this population
      based study, both fatal and nonfatal stroke incidence increased with increasing
      socioeconomic disadvantage. The greater contributor to this incidence pattern was
      nonfatal stroke incidence. This may have implications for service provision to
      those least able to afford it. Area-based identification of those most
      disadvantaged may provide a simple and effective way of targeting regions for
      stroke prevention strategies.

PMID- 16424378
TI  - Upregulated expression of 14-3-3 proteins in astrocytes from human
      cerebrovascular ischemic lesions.
AB  - BACKGROUND AND PURPOSE: Several types of chaperone proteins, such as heat shock
      proteins, have been reported to be associated with brain ischemia. The purpose of
      this study was to investigate whether an abnormal expression of 14-3-3 proteins,
      a novel type of molecular chaperones, occurs in human gray and white matter
      ischemic lesions. METHODS: We prepared formalin-fixed, paraffin-embedded sections
      from 33 autopsied brains, consisting of 7 normal controls, 4 cases with cerebral
      thrombosis, 5 cases with cerebral embolism, 8 cases with multiple lacunar
      infarctions, and 9 cases with Binswanger disease. Deparaffinized sections from
      all cases were immunostained with anti-14-3-3 antibodies using the avidin-biotin
      peroxidase complex method, and some sections were also double-immunostained for
      14-3-3 and glial markers. RESULTS: In the normal control brains, 14-3-3
      immunoreactivity was mainly localized to the neuronal somata and processes.
      Strongly 14-3-3-immunopositive astrocytes were distributed in the infarct lesions
      and were particularly abundant in infarcts at the chronic stage. Intensely 14-3-3
      immunolabeled astrocytes were also observed in the ischemic white matter lesions,
      and in the severely affected white matter lesions from patients with Binswanger
      disease, dense 14-3-3 immunoreactivity was found in clasmatodendritic astroglia
      as well as in reactive astrocytes. CONCLUSIONS: Our results suggest that 14-3-3
      proteins may be induced mainly in astrocytes from human cerebrovascular ischemic
      lesions, and that the upregulated expression of 14-3-3 proteins in astrocytes may
      be involved in the formation of astrogliosis.

PMID- 16424379
TI  - Distinguishing neurocognitive functions in schizophrenia using partially ordered
      classification models.
AB  - Current methods for statistical analysis of neuropsychological test data in
      schizophrenia are inherently insufficient for revealing valid cognitive
      impairment profiles. While neuropsychological tests aim to selectively sample
      discrete cognitive domains, test performance often requires several cognitive
      operations or "attributes." Conventional statistical approaches assign each
      neuropsychological score of interest to a single attribute or "domain" (e.g.,
      attention, executive, etc.), and scores are calculated for each. This can yield
      misleading information about underlying cognitive impairments. We report findings
      applying a new method for examining neuropsychological test data in
      schizophrenia, based on finite partially ordered sets (posets) as classification
      models. A total of 220 schizophrenia outpatients were administered the Positive
      and Negative Symptom Scale (PANSS) and a neuropsychological test battery.
      Selected tests were submitted to cognitive attribute analysis a priori by two
      neuropsychologists. Applying Bayesian classification methods (posets), each
      patient was classified with respect to proficiency on the underlying attributes,
      based upon his or her individual test performance pattern. Twelve cognitive
      "classes" are described in the sample. Resulting classification models provided
      detailed "diagnoses" into "attribute-based" profiles of cognitive
      strength/weakness, mimicking expert clinician judgment. Classification was
      efficient, requiring few measures to achieve accurate classification. Attributes
      were associated with PANSS factors in the expected manner (only the negative and
      cognition factors were associated with the attributes), and a double dissociation
      was observed in which divergent thinking was selectively associated with negative
      symptoms, possibly reflecting a manifestation of Kraepelin's hypothesis regarding
      the impact of volitional disturbances on thought. Using posets for extracting
      more precise cognitive information from neuropsychological data may reveal more
      valid cognitive endophenotypes, while dramatically reducing the amount of testing
      required.

PMID- 16424380
TI  - The antimicrobial/elastase inhibitor elafin regulates lung dendritic cells and
      adaptive immunity.
AB  - Infections with bacteria and viruses such as adenovirus are a feature of chronic
      lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be
      instrumental in the generation of disease exacerbations. We have previously shown
      in acute models that elafin (a lung natural chemotactic molecule for macrophages
      and neutrophils, with potent antimicrobial and neutrophil elastase inhibitor
      activity) is upregulated in infection and modulates innate immunity. Here we
      present data using two independent systems of elafin overexpression in vivo
      (recombinant adenovirus [Ad-elafin] and an elafin transgenic mouse line) to
      examine the function of elafin in adaptive immunity. We show that elafin
      increases the number (immunofluorescence) and activation status (flow cytometric
      measurement) of CD11c+/MHCII+ lung dendritic cells in vivo. Analysis of cytokines
      produced by spleen and lung cells, and of antibodies measured in serum and
      bronchoalveolar lavage fluid, shows that the immunity induced is biased toward a
      type 1 response (production of IL-12, IFN-gamma, and IgG2a). Furthermore, elafin
      overexpression protected mice against further challenge with Ad-LacZ, as assessed
      by antibody levels and neutralization titer, as well as LacZ expression in lung
      tissue. Thus, the pleiotropic molecule elafin has significant potential in
      modulating antigen-presenting cell numbers and activity, and could be beneficial
      in mucosal protective strategies.

PMID- 16424382
TI  - Combination therapy: Synergistic suppression of virus-induced chemokines in
      airway epithelial cells.
AB  - Viruses are associated with the majority of exacerbations of asthma and chronic
      obstructive pulmonary disease. Virus induction of neutrophil and lymphocyte
      chemokines in bronchial epithelium is important in exacerbation pathogenesis.
      Combined corticosteroid/beta2 agonists synergistically suppress airway smooth
      muscle chemokine production. Because bronchial epithelium expresses
      glucocorticoid and beta2 receptors, we investigated whether combination therapy
      can synergistically suppress rhinovirus-induced bronchial epithelial cell
      neutrophil (CXCL5, CXCL8) and lymphocyte (CCL5, CXCL10) chemokine production. We
      investigated modulation of rhinovirus- and IL-1beta-induced bronchial epithelial
      cell chemokine production by salmeterol and fluticasone propionate, used at
      therapeutic concentrations, alone and in combination. After 1 h pretreatment,
      combined treatment significantly inhibited rhinovirus 16, 1B, and IL-1beta
      induced CCL5 and CXCL8 protein and mRNA production in BEAS-2B cells compared with
      fluticasone alone. When used 4 h after treatment, the combination significantly
      reduced virus-induced CCL5 but not CXCL8. Salmeterol alone had no effect;
      therefore, this inhibition was synergistic. Kinetic analysis demonstrated that
      combination therapy reduced by 5-fold the concentration of corticosteroid
      required to inhibit CXCL8 mRNA expression. In primary cells, salmeterol alone
      reduced rhinovirus-induced CCL5 and CXCL10 and increased CXCL5 production in a
      dose-dependent manner but had no effect on CXCL8. Fluticasone alone reduced CCL5,
      CXCL8, and CXCL10 but had no effect on CXCL5. Combination therapy augmented
      inhibition of CXCL8, CCL5, and CXCL10 but had no effect on CXCL5. Corticosteroids
      and beta2 agonists suppress rhinovirus-induced chemokines in bronchial epithelial
      cells through synergistic and additive mechanisms. This effect was greater for
      lymphocyte- than for neutrophil-related chemokines.

PMID- 16424381
TI  - Epidermal growth factor receptor activation by epidermal growth factor mediates
      oxidant-induced goblet cell metaplasia in human airway epithelium.
AB  - Mucus overproduction in inflammatory and obstructive airway diseases is
      associated with goblet cell (GC) metaplasia in airways. Although the mechanisms
      involved in GC metaplasia and mucus hypersecretion are not completely understood,
      association with oxidative stress and epidermal growth factor receptor (EGFR)
      signaling has been reported. To explore the mechanisms involved in oxidative
      stress-induced GC metaplasia, cultures of differentiated normal human bronchial
      epithelial cells grown at the air-liquid interface were exposed to reactive
      oxygen species (ROS) generated by xanthine/xanthine oxidase. EGFR activation and
      signaling was assessed by measuring EGF and transforming growth factor-alpha
      release and EGFR and (44/42)MAPK phosphorylation. The GC population was evaluated
      by confocal microscopy. ROS-induced EGFR activation resulted in GC proliferation
      and increased MUC5AC gene and protein expression. Signaling was due to pro-EGF
      processing by tissue kallikrein (TK), which was activated by ROS-induced
      hyaluronan breakdown. It was inhibited by catalase, a TK inhibitor, and EGF
      blocking antibodies. Exposure to recombinant TK mimicked the ROS effects,
      increasing the expression of MUC5AC and lactoperoxidase. In addition, ROS induced
      the antiapoptotic factor Bcl-2 in a TK-dependent fashion. In conclusion, ROS
      induced GC metaplasia in normal human bronchial epithelial cells is associated
      with HA depolymerization and EGF processing by TK followed by EGFR signaling,
      suggesting that increases in TK activity could contribute to GC metaplasia and
      mucus hypersecretion in diseases such as asthma and chronic bronchitis. The data
      also suggest that increases in GC population could be sustained by the associated
      upregulation of Bcl-2 in airway epithelial cells.

PMID- 16424383
TI  - Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: Role for
      tumor suppressor TSC2.
AB  - The TSC1 and TSC2 proteins, which function as a TSC1/TSC2 tumor suppressor
      complex, are associated with lymphangioleiomyomatosis (LAM), a genetic disorder
      characterized by the abnormal growth of smooth muscle-like cells in the lungs.
      The precise molecular mechanisms that modulate LAM cell growth remain unknown. We
      demonstrate that TSC2 regulates LAM cell growth. Cells dissociated from LAM
      nodules from the lungs of five different patients with LAM have constitutively
      activated S6K1, hyperphosphorylated ribosomal protein S6, activated Erk, and
      increased DNA synthesis compared with normal cells from the same patients. These
      effects were augmented by PDGF stimulation. Akt activity was unchanged in LAM
      cells. Rapamycin, a specific S6K1 inhibitor, abolished increased LAM cell growth.
      The full-length TSC2 was necessary for inhibition of S6 hyperphosphorylation and
      DNA synthesis in LAM cells, as demonstrated by co-microinjection of the C
      terminus, which contains the GTPase activating protein homology domain, and the N
      terminus, which binds TSC1. Our data demonstrate that increased LAM cell growth
      is associated with constitutive S6K1 activation, which is extinguishable by TSC2
      expression. Loss of TSC2 GAP activity or disruption of the TSC1/TSC2 complex
      dysregulates S6K1 activation, which leads to abnormal cell proliferation
      associated with LAM disease.

PMID- 16424384
TI  - Telomerase regulation of myofibroblast differentiation.
AB  - Telomerase activity, which has wide expression in cancerous cells, is induced in
      lung proliferating fibroblasts. It is preferentially expressed in fibroblasts
      versus myofibroblasts. It is unknown whether regulation of telomerase expression
      is related to the process of fibroblast differentiation into myofibroblasts. The
      objective of this study was to clarify such a potential link between telomerase
      expression and myofibroblast differentiation. Telomerase inhibitor, 3'-azido
      2',3'-dideoxythymidine, or antisense oligonucleotide to the telomerase RNA
      component was used to inhibit the induced fibroblast telomerase activity. The
      results showed that inhibition of induced telomerase increased alpha-smooth
      muscle actin expression, an indicator of myofibroblast differentiation. In
      contrast, induction of telomerase by basic fibroblast growth factor inhibited
      alpha-smooth muscle actin expression. These findings suggest that the loss of
      telomerase activity is closely associated with myofibroblast differentiation and
      possibly functions as a trigger for myofibroblast differentiation. Conversely,
      expression of telomerase suppresses myofibroblast differentiation.

PMID- 16424385
TI  - B lymphocytes are critical for lung fibrosis control and prostaglandin E2
      regulation in IL-9 transgenic mice.
AB  - We previously showed that overexpression of IL-9 controls lung fibrosis induced
      by silica particles in mice (Arras and colleagues; Am J Respir Cell Mol Biol
      2001;24:368-375). This protection was associated with an expansion of lung B
      lymphocytes. To explore the contribution of these cells in the protective effect
      of IL-9, we crossed IL-9 transgenic (IL-9+) and B-deficient (B-) mice. The
      antifibrotic effect of IL-9 was abolished in mice deficient in B lymphocytes (B
      IL-9+) and restored by reconstituting these mice with B lymphocytes. The
      expression of the antifibrotic mediator prostaglandin (PG)E2 was markedly
      increased in the lung of IL-9+ mice at baseline, and similarly high levels were
      found in both wild-type and transgenic strains upon silica treatment. This PGE2
      expression was completely abolished in B- mice, both at baseline and upon silica
      administration. In vitro, alveolar and peritoneal macrophages from IL-9+ mice had
      an increased capacity to produce PGE2 in response to LPS or silica. This capacity
      was markedly reduced in macrophages obtained from B- mice and restored by co
      incubating macrophages with B lymphocytes from IL-9+ mice. The increased PGE2
      response of IL-9+ macrophages was dependent on cyclooxygenase 2 expression, based
      on transcript analysis and inhibition by NS398. We conclude that B lymphocytes
      are essential for the protection against lung fibrosis and macrophage
      overexpression of PGE2 in IL-9 transgenic animals.

PMID- 16424386
TI  - Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps
      of NF-kappaB activation.
AB  - The Tax oncoprotein plays a crucial role in the proliferation and transformation
      of human T-cell leukemia virus type I (HTLV-I)-infected T lymphocytes through
      various mechanisms, including activation of the nuclear factor (NF)-kappaB
      pathway. We found that cytoplasmic ubiquitylation of Tax C-terminal lysines is
      critical for Tax binding to the IkappaB kinase complex and subsequent nuclear
      translocation of RelA. Conversely, we demonstrate that the same lysines are
      sumoylated in the nucleus, an event required for the formation of RelA/p300
      enriched Tax nuclear bodies and full NF-kappaB transcriptional activation. In
      contrast, Tax ubiquitylation and sumoylation are dispensable for its activation
      of cyclic adenosine monophosphate response element binding protein (CREB)
      dependent genes. Thus, ubiquitylation and sumoylation of the same residues of Tax
      regulate 2 essential steps controlling NF-kappaB activation, demonstrating how
      these posttranslational modifications can cooperate to promote Tax-induced
      transformation.

PMID- 16424387
TI  - Global transcriptional coactivators CREB-binding protein and p300 are highly
      essential collectively but not individually in peripheral B cells.
AB  - CREB-binding protein (CBP) and its para-log p300 are transcriptional coactivators
      that physically or functionally interact with over 320 mammalian and viral
      proteins, including 36 that are essential for B cells in mice. CBP and p300 are
      generally considered limiting for transcription, yet their roles in adult cell
      lineages are largely unknown since homozygous null mutations in either gene or
      compound heterozygosity cause early embryonic lethality in mice. We tested the
      hypotheses that CBP and p300 are limiting and that each has unique properties in
      B cells, by using mice with Cre/LoxP conditional knockout alleles for CBP
      (CBP(flox)) and p300 (p300(flox)), which carry CD19(Cre) that initiates floxed
      gene recombination at the pro-B-cell stage. CD19(Cre)-mediated loss of CBP or
      p300 led to surprisingly modest deficits in B-cell numbers, whereas inactivation
      of both genes was not tolerated by peripheral B cells. There was a moderate
      decrease in B-cell receptor (BCR)-responsive gene expression in CBP or p300
      homozygous null B cells, suggesting that CBP and p300 are essential for this
      signaling pathway that is crucial for B-cell homeostasis. These results indicate
      that individually CBP and p300 are partially limiting beyond the pro-B-cell stage
      and that other coactivators in B cells cannot replace their combined loss.

PMID- 16424388
TI  - Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense
      coded protein of HTLV-1.
AB  - Natural antisense viral transcripts have been recognized in retroviruses,
      including human T-cell leukemia virus type 1 (HTLV-1), HIV-1, and feline
      immunodeficiency virus (FIV), and have been postulated to encode proteins
      important for the infection cycle and/or pathogenesis of the virus. The antisense
      strand of the HTLV-1 genome encodes HBZ, a novel nuclear basic region leucine
      zipper (b-ZIP) protein that in overexpression assays down-regulates Tax
      oncoprotein-induced viral transcription. Herein, we investigated the contribution
      of HBZ to HTLV-1-mediated immortalization of primary T lymphocytes in vitro and
      HTLV-1 infection in a rabbit animal model. HTLV-1 HBZ mutant viruses were
      generated and evaluated for viral gene expression, protein production, and
      immortalization capacity. Biologic properties of HBZ mutant viruses in vitro were
      indistinguishable from wild-type HTLV-1, providing the first direct evidence that
      HBZ is dispensable for viral replication and cellular immortalization. Rabbits
      inoculated with irradiated cells expressing HTLV-1 HBZ mutant viruses became
      persistently infected. However, these rabbits displayed a decreased antibody
      response to viral gene products and reduced proviral copies in peripheral blood
      mononuclear cells (PBMCs) as compared with wild-type HTLV-1-infected animals. Our
      findings indicated that HBZ was not required for in vitro cellular
      immortalization, but enhanced infectivity and persistence in inoculated rabbits.
      This study demonstrates that retroviruses use negative-strand-encoded proteins in
      the establishment of chronic viral infections.

PMID- 16424389
TI  - Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the
      germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases
      included in the German BFM (Berlin-Frankfurt-Munster) Multicenter Trial.
AB  - Diffuse large B-cell lymphoma (DLBCL) in adults is a heterogeneous disease.
      Biologic subgroups of DLBCL with a favorable prognosis (germinal center B-cell
      like, GCB) and with a poor prognosis (activated B-cell-like, ABC) have been
      defined by gene expression profiling and can be distinguished by
      immunohistochemistry. In contrast to their adult counterparts, children with
      DLBCL have an excellent prognosis. We analyzed 63 cases of DLBCL in pediatric
      patients by immunohistochemistry and fluorescence in situ hybridization (FISH)
      and found a striking predominance of a GCB subtype, which might explain the good
      clinical outcome in these lymphomas. Interestingly, FISH applied to 50 of these
      cases, as well as conventional cytogenetics available in 3 cases, revealed
      absence of the translocation t(14;18) involving the BCL2 gene, which is present
      in about 15% of adult GCB subtype DLBCL. Our data indicate that pediatric DLBCL
      differs from adult DLBCL and might comprise a biologically unique subgroup of
      DLBCL from which important insights into the pathogenesis and biology of this
      disease might be gained.

PMID- 16424390
TI  - Ligand-induced internalization selects use of common receptor neuropilin-1 by
      VEGF165 and semaphorin3A.
AB  - Neuropilin-1 (Npn-1) is a receptor shared by class 3 semaphorins and heparin
      binding forms of vascular endothelial growth factor (VEGF), protein families that
      regulate endothelial and neuronal-cell function. Ligand interaction with Npn-1
      dictates the choice of signal transducer; plexins transduce semaphorin signals,
      and VEGF receptors transduce VEGF signals. It is not clear how class 3
      semaphorins affect endothelial-cell function and how the shared receptor Npn-1
      selects its ligand. We report that semaphorin3A (Sema3A) inhibits endothelial
      cell lamellipodia formation, adhesion, survival, proliferation, and cord
      formation. VEGF(165), but not VEGF(121), could block all these effects of Sema3A.
      VEGF(165) competed with Sema3A for binding to endothelial cells, effectively
      reduced cell-surface Npn-1, and promoted its internalization. Use of soluble
      forms of Npn-1 or VEGF receptor-1 to block VEGF(165) binding to Npn-1 or to VEGF
      receptors provided evidence that surface Npn-1 and VEGF receptors are required
      for VEGF(165)-induced Npn-1 internalization. Sema3A also reduced cell-surface Npn
      1 in endothelial cells and promoted its internalization, but required a higher
      concentration than VEGF(165). These results demonstrate that preferential
      receptor binding and internalization by a ligand are mechanisms by which the
      common receptor Npn-1 can play an essential role in prioritizing conflicting
      signals.

PMID- 16424392
TI  - Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B
      cell lymphomas.
AB  - The PR (PRDI-BF1-RIZ) domain zinc finger protein 1 (PRDM1) is a transcription
      repressor with a pivotal role in plasma-cell differentiation. We identified
      clonal inactivating mutations in PRDM1 in the diffuse large B-cell lymphoma
      (DLBCL) cell line OCI-Ly3 and in 8 of 35 de novo clinical DLBCL samples. The
      mutational spectrum consists predominantly (7 cases) of single-nucleotide
      mutations affecting consensus splice donor sites, some of which are recurrent,
      that lead to splicing aberrations and premature translation termination. In 2 of
      these cases, point mutations appear to be caused by RNA editing with G-to-A and U
      to-G conversions. Other mutations include frame-shift deletion and chromosomal
      inversion. Except for one mutant, which may act as a dominant-negative, all
      mutations are associated with either deletion or silencing of the paired PRDM1
      allele. This study identifies PRDM1 inactivation as a recurrent genetic defect in
      DLBCL cells and establishes PRDM1 as a potential tumor suppressor gene in DLBCL.
      Moreover, it implies inhibition of terminal differentiation as a pathogenetic
      pathway in DLBCL, particularly for the activated B-cell-like DLBCL. It also
      demonstrates for the first time the potential role of RNA editing in
      lymphomagenesis.

PMID- 16424391
TI  - Synergistic activity of the proteasome inhibitor PS-341 with non-myeloablative
      153-Sm-EDTMP skeletally targeted radiotherapy in an orthotopic model of multiple
      myeloma.
AB  - Multiple myeloma is a highly radiosensitive skeletal malignancy, but bone-seeking
      radionuclides have not yet found their place in disease management. We previously
      reported that the proteasome inhibitor PS-341 selectively sensitizes myeloma
      cells to the lethal effects of ionizing radiation. To extend these observations
      to an in vivo model, we combined PS-341 with the bone-seeking radionuclide 153-Sm
      EDTMP. In vitro clonogenic assays demonstrated synergistic killing of myeloma
      cells exposed to both PS-341 and 153-Sm-EDTMP. Using the orthotopic, syngeneic
      5TGM1 myeloma model, the median survivals of mice treated with saline, 2 doses of
      PS-341 (0.5 mg/kg), or a single nonmyeloablative dose of 153-Sm-EDTMP (22.5 MBq)
      were 21, 22, and 28 days, respectively. In contrast, mice treated with
      combination therapy comprising 2 doses of PS-341 (0.5 mg/kg), 1 day prior to and
      1 day following 153-Sm-EDTMP (22.5 MBq) showed a significantly prolonged median
      survival of 49 days (P < .001). In addition to prolonged survival, this treatment
      combination yielded reduced clonogenicity of bone marrow-resident 5TGM1 cells,
      reduced serum myeloma-associated paraprotein levels, and better preservation of
      bone mineral density. Myelosuppression, determined by peripheral blood cell
      counts and clonogenicity assays of hematopoietic progenitors, did not differ
      between animals treated with 153-Sm-EDTMP alone versus those treated with the
      combination of PS-341 plus 153-Sm-EDTMP. PS-341 is a potent, selective in vivo
      radiosensitizer that may substantially affect the efficacy of skeletal-targeted
      radiotherapy in multiple myeloma.

PMID- 16424393
TI  - Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling
      hematopoietic stem cell transplantation: effect on long-term outcome is confirmed
      in 2 independent cohorts and may be modulated by the type of gastrointestinal
      decontamination.
AB  - To assess the role of NOD2/CARD15 variants on the long-term outcome of allogeneic
      stem cell transplantation in a genetically homogeneous group, we extended our
      previous study (cohort I, n = 78) and typed DNA for NOD2/CARD15 single nucleotide
      polymorphisms (SNPs) from an additional 225 recipients and their HLA-identical
      sibling donors (cohort II) treated at four other European centers. Results of
      genotyping were compared with clinical outcome. The strong association of
      NOD2/CARD15 variants with transplantation-related mortality (TRM) was confirmed
      in univariate and multivariate analysis; TRM increased from 20% in cohort I/22%
      in cohort II in recipient/donor pairs without any NOD2/CARD15 variants to 47% in
      cohort I/32% in cohort II in the presence of one variant in either donor or
      recipient and further to 57% in cohort I/74% in cohort II in the presence of 2 or
      more variants (P < .002 in both cohorts). NOD2/CARD15 SNPs were not associated
      with relapse rate but had a strong impact on overall survival. In an analysis of
      center effects, the type of gastrointestinal decontamination was the only factor
      interfering with the prognostic significance of NOD2/CARD15 SNPs. Our data
      further support an interaction between gastrointestinal defense mechanisms,
      activation of the innate immune system, and specific transplant-related
      complications.

PMID- 16424395
TI  - Remodeling the regulation of iron metabolism during erythroid differentiation to
      ensure efficient heme biosynthesis.
AB  - Terminal erythropoiesis is accompanied by extreme demand for iron to ensure
      proper hemoglobinization. Thus, erythroblasts must modify the "standard" post
      transcriptional feedback regulation, balancing expression of ferritin (Fer; iron
      storage) versus transferrin receptor (TfR1; iron uptake) via specific mRNA
      binding of iron regulatory proteins (IRPs). Although erythroid differentiation
      involves high levels of incoming iron, TfR1 mRNA stability must be sustained and
      Fer mRNA translation must not be activated because iron storage would counteract
      hemoglobinization. Furthermore, translation of the erythroid-specific form of
      aminolevulinic acid synthase (ALAS-E) mRNA, catalyzing the first step of heme
      biosynthesis and regulated similarly as Fer mRNA by IRPs, must be ensured. We
      addressed these questions using mass cultures of primary murine erythroid
      progenitors from fetal liver, either undergoing sustained proliferation or highly
      synchronous differentiation. We indeed observed strong inhibition of Fer mRNA
      translation and efficient ALAS-E mRNA translation in differentiating
      erythroblasts. Moreover, in contrast to self-renewing cells, TfR1 stability and
      IRP mRNA binding were no longer modulated by iron supply. These and additional
      data stemming from inhibition of heme synthesis with succinylacetone or from iron
      overload suggest that highly efficient utilization of iron in mitochondrial heme
      synthesis during normal erythropoiesis alters the regulation of iron metabolism
      via the IRE/IRP system.

PMID- 16424394
TI  - Hepatocyte growth factor is a lymphangiogenic factor with an indirect mechanism
      of action.
AB  - Hepatocyte growth factor (HGF) has previously been reported to act as a
      hemangiogenic factor, as well as a mitogenic factor for a variety of tumor cells.
      Here, we demonstrate that HGF is a lymphangiogenic factor, which may contribute
      to lymphatic metastasis when overexpressed in tumors. In a mouse corneal
      lymphangiogenesis model, implantation of HGF induces sprouting and growth of new
      lymphatic vessel expressing the lymphatic vessel endothelial specific marker
      hyaluronan receptor-1 (Lyve-1). Unlike blood vessels, the Lyve-1-positive
      structures consist of blunt-ended vessels of large diameters that generally lack
      expression of CD31. The growth of HGF-induced lymphatic vessels can be partially
      blocked by a soluble VEGFR-3, suggesting that HGF may stimulate lymphatic vessel
      growth through an indirect mechanism. Consistent with this finding, the HGF
      receptor (c-Met) is only localized on corneal blood vessels but is absent on
      lymphatic vessels in a mouse corneal assay. In a transgenic mouse model that
      expresses HGF under the control of the whey acidic protein (WAP) gene promoter,
      transgenic females develop tumors in the mammary glands after several
      pregnancies. Interestingly, dilated Lyve-1-positive lymphatic vessels accumulate
      in the peritumoral area and occasionally penetrate into the tumor tissue. Our
      findings indicate that HGF may play a critical role in lymphangiogenesis and
      potentially contribute to lymphatic metastasis.

PMID- 16424397
TI  - p38 mitogen-activated protein kinase activity commits embryonic stem cells to
      either neurogenesis or cardiomyogenesis.
AB  - Mouse embryonic stem (ES) cells can be differentiated, in vitro into a variety of
      cell types including cardiac cells and neurons. This process is strictly
      controlled by the potent morphogen retinoic acid (RA). At a concentration of 10(
      7) M, RA induces ES cell differentiation into neurons and, conversely, inhibits
      cardiomyogenesis. We found that p38 mitogen-activated protein kinase (p38MAPK)
      activity peaked spontaneously, between day 3 and day 5, during ES cell
      differentiation and that RA completely inhibited this peak of activity. In
      contrast to wild-type cells, which required RA treatment, p38alpha(-/-) ES cells
      differentiated spontaneously into neurons and did not form cardiomyocytes.
      Moreover, inhibition of the peak of p38MAPK activity by a specific inhibitor,
      PD169316, committed ES cells into the neuronal lineage and blocked
      cardiomyogenesis. By genetic and biochemical approaches, we demonstrate that, in
      two different ES cell lines, the control of p38MAPK activity constitutes an early
      switch, committing ES cells into either neurogenesis (p38 off) or
      cardiomyogenesis (p38 on).

PMID- 16424396
TI  - Enhanced de novo neurogenesis and dopaminergic neurogenesis in the substantia
      nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease
      like mice.
AB  - Research reports on de novo neurogenesis, particularly dopaminergic (DA)
      neurogenesis in the adult mammalian substantia nigra (SN), remain very
      controversial. For this reason, we used the nestin second intron enhancer
      controlled LacZ reporter transgenic mouse model coupled with the 1-methyl-4
      phyenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion system to investigate whether
      there are neurogenesis and DA neurogenesis in the SN of the adult normal and
      Parkinson's disease (PD)-like mice. First, we demonstrated the presence of neural
      progenitor cells (NPCs), basal levels of neurogenesis, and DA neurogenesis in the
      normal adult mouse SN. Second, we showed that there is not only a significant
      increase in the number of NPCs but also a dramatic increase of neurogenesis from
      the NPCs in the SN and the midline region adjacent to the SN of the PD-like mice
      compared with that of normal controls. More importantly, we also demonstrated
      that there is an increase of DA neurogenesis in the SN of the MPTP-lesioned mice.
      Third, we showed that the increased DA neurogenesis in the MPTP-lesioned mice was
      derived from the NPCs and 5-bromodeoxyuridine-positive cells, suggesting that
      multiple stem cell lineages may contribute to the enhanced neurogenesis in the
      adult SN. Taken together, these results establish that there are basal levels,
      albeit low, and increased levels of de novo neurogenesis and DA neurogenesis in
      the SN of the adult normal and PD-like mice, respectively. The increased NPCs in
      the MPTP-lesioned mice further suggest that experimental approaches to promote de
      novo neurogenesis may provide an effective therapy for PD by functional
      replacement of degenerated DA neurons.

PMID- 16424398
TI  - Gap junction protein connexin 43 serves as a negative marker for a stem cell
      containing population of human limbal epithelial cells.
AB  - This study evaluated whether the gap junction protein connexin (Cx) 43 could
      serve as a negative cell surface marker for human corneal epithelial stem cells.
      Cx43 expression was evaluated in corneo-limbal tissue and primary limbal
      epithelial cultures. Immunofluorescent staining and laser scanning confocal
      microscopy showed that Cx43 was strongly expressed in the corneal and limbal
      suprabasal epithelial cells, but the basal cells of the limbal epithelium were
      negative. Cx43 antibody stained mainly large cells but not small cells in primary
      limbal epithelial cultures. As determined by semiquantitative reverse
      transcription polymerase chain reaction (PCR) and real-time PCR, Cx43 mRNA was
      more abundant in the corneal than limbal epithelia, and it was expressed in
      higher levels in mature limbal epithelial cultures. Using GAP11, a rabbit
      polyclonal antibody against the Cx32 extracellular loop 2 (151-187), a sequence
      that is highly homologous in Cx43, the Cx43(dim) and Cx43(bright) cells were
      selected from primary limbal epithelial cultures by fluorescence-activated cell
      sorting and were evaluated for stem cell properties. These Cx43(dim) and
      Cx43(bright) cells were confirmed by their expression levels of Cx43 protein and
      mRNA. The Cx43(dim) cells were found to contain higher percentages of slow
      cycling bromodeoxyuridine (BrdU)-label retaining cells and the cells that were
      positive for stem cell-associated markers p63, ABCG2, and integrin beta1 and
      negative for differentiation markers K3 and involucrin. The Cx43(dim) cells
      possessed a greater proliferative potential than Cx43(bright) cells and
      nonfractionated cells as evaluated by BrdU incorporation, colony-forming
      efficiency, and growth capacity. Our findings suggest that human limbal basal
      cells do not express connexin 43, which could serve as a negative cell surface
      marker for the stem cell-containing population of human limbal epithelial cells.

PMID- 16424400
TI  - Human serum from platelet-poor plasma for the culture of primary human
      preadipocytes.
AB  - In adipose tissue engineering, the use of human serum is essential to achieve the
      goal of an autologous system. Serum from conventional human plasma (SCP) contains
      platelet-derived growth factor (PDGF), a growth factor known to be both a potent
      inhibitor of adipose differentiation and also the most important stimulator of
      proliferation in human serum. Serum from platelet-poor plasma (SPPP) is
      considered to be PDGF-deprived and should therefore inhibit the differentiation
      of preadipocytes to adipocytes to a lesser extent. Effective cultivation of
      preadipocytes with SPPP requires compensating for the missing stimulatory PDGF
      effect on proliferation. However, the addition of other growth factors to the
      media needs to provide stimulation of proliferation without significant
      inhibition of differentiation. Primary human preadipocytes were isolated from
      adipose tissue samples of 10 healthy human donors and cultured under four
      different medium conditions (SCP, SPPP, SPPP + 1 nM basic fibroblast growth
      factor [bFGF], and SPPP + 1 nM epidermal growth factor [EGF]) for five
      generations. Proliferation activity and differentiation capacity were assessed
      for each sample, generation, and culture condition by calculating doubling time
      and measuring glycerol-3-phosphate dehydrogenase (GPDH)-specific activity. The
      use of SPPP resulted in a marked rise in GPDH activity compared with the cells
      cultured with SCP. Supplementing SPPP with 1 nM bFGF or EGF increased
      proliferation activity significantly. SPPP can be considered superior to SCP for
      the culture of primary human preadipocytes in adipose tissue engineering in terms
      of proliferation activity and differentiation capacity.

PMID- 16424399
TI  - Selenium supplementation restores the antioxidative capacity and prevents cell
      damage in bone marrow stromal cells in vitro.
AB  - Bone marrow stromal cells (BMSCs) and other cell populations derived from
      mesenchymal precursors are developed for cell-based therapeutic strategies and
      undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS)
      of cellular and environmental origin are involved in redox signaling, cumulative
      cell damage, senescence, and tumor development. Selenium-dependent (glutathione
      peroxidases [GPxs] and thioredoxin reductases [TrxRs]) and selenium-independent
      (superoxide dismutases [SODs] and catalase [CAT]) enzyme systems regulate
      cellular ROS steady state levels. SODs process superoxide anion to hydrogen
      peroxide, which is subsequently neutralized by GPx and CAT; TrxR neutralizes
      other ROS, such as peroxinitrite. Primary BMSCs and telomerase-immortalized human
      mesenchymal stem cells (hMSC-TERT) express GPx1-3, TrxR1, TrxR2, SOD1, SOD2, and
      CAT. We show here that in standard cell cultures (5%-10% fetal calf serum, 5-10
      nM selenite), the activity of antioxidative selenoenzymes is impaired in hMSC
      TERT and BMSCs. Under these conditions, the superoxide anion processing enzyme
      SOD1 is not sufficiently stimulated by an ROS load. Resulting oxidative stress
      favors generation of micronuclei in BMSCs. Supplementation of selenite (100 nM)
      restores basal GPx and TrxR activity, rescues basal and ROS-stimulated SOD1 mRNA
      expression and activity, and reduces ROS accumulation in hMSC-TERT and
      micronuclei generation in BMSCs. In conclusion, BMSCs in routine cell culture
      have low antioxidative capacity and are subjected to oxidative stress, as
      indicated by the generation of micronuclei. Selenite supplementation of BMSC
      cultures appears to be an important countermeasure to restore their antioxidative
      capacity and to reduce cell damage in the context of tissue engineering and
      transplantation procedures.

PMID- 16424402
TI  - Beta2 deja vu.

PMID- 16424403
TI  - COPD, inflammation and its modulation by phosphodiesterase 4 inhibitors: time to
      look beyond the FEV1.

PMID- 16424405
TI  - "What's in the black box?".

PMID- 16424404
TI  - Blue light special on CPAP, aisle 11.

PMID- 16424406
TI  - American College of Chest Physicians evidence-based guidelines--the next
      generation: considering resource use and evolution to a single grading system.

PMID- 16424407
TI  - Nasopharyngeal detection of severe acute respiratory syndrome-associated
      coronavirus RNA in health-care workers.

PMID- 16424410
TI  - Formoterol, 24 microg bid, and serious asthma exacerbations: similar rates
      compared with formoterol, 12 microg bid, with and without extra doses taken on
      demand, and placebo.
AB  - STUDY OBJECTIVES: The primary objective was to determine whether high-dose
      formoterol, 24 mug bid, was associated with more asthma exacerbations compared
      with lower formoterol doses in patients with stable persistent asthma. Serious
      asthma exacerbations (life threatening or requiring hospitalization) were the
      primary end point. Secondary end points included significant exacerbations
      requiring systemic corticosteroids, all exacerbations, and changes in FEV1.
      DESIGN: In a multicenter, placebo-controlled, parallel-group study, patients were
      randomized to 16 weeks of treatment with formoterol, 24 microg bid; formoterol,
      12 microg bid, with up to two additional 12-microg doses daily on demand for
      worsening symptoms (12 microg bid plus on demand); formoterol, 12 microg bid; or
      placebo. The formoterol 12-microg-bid plus on-demand regimen was administered
      open label, while the other three regimens were double blind. SETTING: Outpatient
      clinics. PATIENTS: A total of 2,085 patients aged > or = 12 years with stable,
      persistent asthma were enrolled and treated; 65% (n = 1,347) received regular
      concomitant antiinflammatory therapy during the study. MEASUREMENTS AND RESULTS:
      Nine patients had respiratory-related serious adverse events (SAEs) requiring
      hospitalization: two patients (0.4%) in the 24-microg-bid group; one patient
      (0.2%) in the 12-microg-bid plus on-demand group; five patients (0.9%) in the 12
      microg-bid group; and one patient (0.2%) in the placebo group. All of these
      events were asthma related, except for two SAEs in the 12-microg-bid group that
      were later considered not to be asthma related by independent reviewers who were
      not associated with the conduct of the study. The proportions of patients with
      significant asthma exacerbations (requiring systemic corticosteroids) were
      similar in the 24-microg-bid group (6.3%, 33 of 527 patients), 12-microg-bid
      group (5.9%, 31 of 527 patients) and placebo group (8.8%, 45 of 514 patients) and
      lower in the 12-microg-bid plus on-demand group (4.4%, 23 of 517 patients; p =
      0.0057 vs placebo). All treatments were well tolerated. All formoterol treatment
      regimens had a significant effect on FEV1 measured 2 h after dose during the
      study (p < 0.0001 vs placebo); and on predose trough FEV1 measured at all visits
      after baseline (p < 0.002 vs placebo). CONCLUSIONS: Treatment with formoterol, 24
      microg bid, was not associated with an increase in serious asthma exacerbations
      compared with the lower formoterol doses or placebo.

PMID- 16424409
TI  - The Salmeterol Multicenter Asthma Research Trial: a comparison of usual
      pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.
AB  - STUDY OBJECTIVE: To compare the safety of salmeterol xinafoate or placebo added
      to usual asthma care. DESIGN: A 28-week, randomized, double-blind, placebo
      controlled, observational study. SETTING: Study subjects were seen once in the
      study physician's office for screening and were provided all blinded study
      medication for the entire study period. Follow-up by telephone was scheduled
      every 4 weeks. PARTICIPANTS: Subjects (> 12 years old) with asthma as judged by
      the study physician were eligible. Individuals with a history of long-acting
      beta2-agonist use were excluded. INTERVENTIONS: Salmeterol, 42 mug bid via
      metered-dose inhaler (MDI), and placebo bid via MDI. MEASUREMENTS AND RESULTS:
      Following an interim analysis in 26,355 subjects, the study was terminated due to
      findings in African Americans and difficulties in enrollment. The occurrence of
      the primary outcome, respiratory-related deaths, or life-threatening experiences
      was low and not significantly different for salmeterol vs placebo (50 vs 36;
      relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was
      a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16;
      95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25
      to 15.34), and in combined asthma-related deaths or life-threatening experiences
      (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs
      placebo. The imbalance occurred largely in the African-American subpopulation:
      respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10;
      95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening
      experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving
      salmeterol vs placebo. CONCLUSIONS: For the primary end point in the total
      population, there were no significant differences between treatments. There were
      small, but statistically significant increases in respiratory-related and asthma
      related deaths and combined asthma-related deaths or life-threatening experiences
      in the total population receiving salmeterol. Subgroup analyses suggest the risk
      may be greater in African Americans compared with Caucasian subjects. Whether
      this risk is due to factors including but not limited to a physiologic treatment
      effect, genetic factors, or patient behaviors leading to poor outcomes remains
      unknown.

PMID- 16424411
TI  - Protective effect of fish oil supplementation on exercise-induced
      bronchoconstriction in asthma.
AB  - BACKGROUND: Previous research has demonstrated that fish oil supplementation has
      a protective effect on exercise-induced bronchoconstriction (EIB) in elite
      athletes, which may be attributed to its antiinflammatory properties. Since EIB
      in asthma involves proinflammatory mediator release, it is feasible that fish oil
      supplementation may reduce the severity of EIB in asthmatic subjects. STUDY
      OBJECTIVES: To determine the efficacy of fish oil supplementation on severity of
      EIB in subjects with asthma. DESIGN: Randomized, double-blind, crossover study.
      SETTING: Lung function and exercise testing in a university research laboratory.
      PATIENTS AND MEASUREMENTS: Sixteen asthmatic patients with documented EIB entered
      the study on their normal diet and then received either fish oil capsules
      containing 3.2 g of eicosapentaenoic acid and 2.0 g of docohexaenoic acid (fish
      oil diet, n = 8) or placebo capsules (placebo diet, n = 8) daily for 3 weeks. At
      the beginning of the study (normal diet) and at the end of each treatment phase,
      the following pre-exercise and postexercise measures were assessed: (1) pulmonary
      function; (2) induced sputum differential cell count percentage and
      proinflammatory eicosanoid metabolite (leukotriene C4 [LTC4]-leukotriene E4
      [LTE4] and prostaglandin D2 [PGD2]) and cytokine (interleukin [IL]-1beta and
      tumor necrosis factor [TNF]-alpha) concentrations; and (3) eicosanoid metabolites
      leukotriene B4 (LTB4) and leukotriene B5 (LTB(5)) generation from activated
      polymorphonuclear leukocytes (PMNLs). RESULTS: On the normal and placebo diet,
      subjects exhibited EIB. However, the fish oil diet improved pulmonary function to
      below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator
      use. Induced sputum differential cell count percentage and concentrations of LTC4
      LTE4, PGD2, IL-1beta, and TNF-alpha were significantly reduced before and
      following exercise on the fish oil diet compared to the normal and placebo diets.
      There was a significant reduction in LTB4 and a significant increase in LTB5
      generation from activated PMNLs on the fish oil diet compared to the normal and
      placebo diets. CONCLUSION: Our data suggest that fish oil supplementation may
      represent a potentially beneficial nonpharmacologic intervention for asthmatic
      subjects with EIB.

PMID- 16424412
TI  - Sex differences in the presentation and course of asthma hospitalizations.
AB  - OBJECTIVE: To distinguish between differences in prevalence, asthma severity, and
      treatment to explain sex-related differences in hospitalized asthma patients.
      DESIGN: Medical record review. SETTING: Thirty US hospitals as part of the
      University HealthSystem Consortium Asthma Clinical Benchmarking Project.
      PATIENTS: A random sample of patients aged 2 to 54 years and admitted to the
      hospital for acute asthma from 1999 to 2000. MEASUREMENTS: Demographics, medical
      history, initial oxygen saturation, initial peak expiratory flow (adults),
      initial pulmonary index (children), emergency department course, length of
      hospital stay, and discharge plans. RESULTS: The cohort included 606 pediatric
      (aged 2 to 17 years) and 680 adult (aged 18 to 54 years) inpatients. The sex
      ratio varied significantly by age: 40% were girls 2 to 17 years of age, and 68%
      were women 18 to 54 years of age p < 0.001). Among children, girls did not differ
      from boys according to asthma history, pulmonary index scores, or hospital length
      of stay. Among adults, women were more likely to have a primary care provider
      (90% vs 73%, p < 0.001) but did not differ according to asthma history or recent
      medication use. Women had a higher mean initial PEF compared to men (43% of
      predicted vs 36% of predicted, p < 0.001) and higher median initial oxygen
      saturation (95% vs 93%, p = 0.002) but did not differ by hospital length of stay.
      No sex differences in discharge regimens were identified in children or adults.
      CONCLUSIONS: Among US inpatients with acute asthma, male children are more common
      than female children, while women are more common in adults. The results in
      children are probably explained by prevalence differences, since no sex
      differences were seen in markers of asthma severity or treatment. In adults,
      increased symptoms in response to a given level of airway obstruction in women
      may contribute to the female predominance in asthma hospitalizations.

PMID- 16424413
TI  - Cilomilast for COPD: results of a 6-month, placebo-controlled study of a potent,
      selective inhibitor of phosphodiesterase 4.
AB  - BACKGROUND: COPD is a relentless, progressive disease. This study evaluated the
      efficacy of cilomilast, a selective phosphodiesterase (PDE) 4 inhibitor, in the
      treatment of COPD. METHODS: This was a randomized, double-blind, placebo
      controlled, parallel-group, multicenter study in subjects with COPD. After a 4
      week, single-blind, placebo run-in period, eligible subjects were randomized in a
      2:1 ratio to receive oral cilomilast, 15 mg bid, or placebo for 24 weeks.
      Subjects between 40 and 80 years of age who had received a diagnosis of COPD were
      eligible for the study. The primary efficacy variables were changes from baseline
      in trough (ie, predose) FEV1 and in total score of the St. George's Respiratory
      Questionnaire (SGRQ). A key secondary end point was the incidence rate of COPD
      exacerbations. RESULTS: The average change from baseline in FEV1 over 24 weeks in
      the cilomilast group was an increase of 10 mL compared with a decrease of 30 mL
      in the placebo group (difference, 40 mL; p = 0.002). When averaged over 24 weeks,
      there was a clinically significant reduction in the mean total SGRQ score in
      subjects receiving cilomilast therapy, with a difference of 4.1 U compared with
      subjects who received placebo (p = 0.001). A greater percentage of subjects in
      the cilomilast group were exacerbation-free at 24 weeks (74%; p = 0.008) compared
      with placebo (62%). Adverse events were generally mild or moderate and were not
      unexpected for this class of medications. GI adverse events that interfered with
      daily activities (cilomilast, 17%; placebo, 8%) predominantly occurred within the
      first 3 weeks of initiating cilomilast therapy. CONCLUSION: Cilomilast is an
      orally active, potent, and selective inhibitor of PDE-4. Cilomilast maintained
      pulmonary function and improved health status, and reduced the rate of COPD
      exacerbations during 24 weeks of treatment. This study supports the use of
      cilomilast, a novel, selective PDE-4 inhibitor, in subjects with COPD.

PMID- 16424414
TI  - A continuous positive airway pressure trial as a novel approach to the diagnosis
      of the obstructive sleep apnea syndrome.
AB  - OBJECTIVES: Treatment of obstructive sleep apnea syndrome (OSA) is often delayed
      because polysomnography, the recommended standard diagnostic test, is not readily
      available. We evaluated whether the diagnosis of sleep apnea could be inferred
      from the response to a treatment trial with nasal continuous positive airway
      pressure (CPAP). DESIGN: Study on diagnostic accuracy. SETTING: Sleep-disorders
      clinic of a university hospital. PATIENTS: Seventy-six sleepy snorers
      consecutively referred for sleep apnea evaluation. INTERVENTIONS: CPAP treatment
      trial over 2 weeks as an initial diagnostic test in comparison with
      polysomnography, and treatment success over > or = 4 months. MEASUREMENTS AND
      RESULTS: The main outcome was diagnostic accuracy of the CPAP trial. The trial
      result was positive if the patient had used CPAP for > 2 h per night and wished
      to continue therapy. This suggested sleep apnea. The trial was evaluated in terms
      of predicting an obstructive apnea/hypopnea index (AHI) > 10/h during
      polysomnography performed for validation, and in terms of identifying sleep apnea
      patients treated successfully over > or = 4 months. Forty-four of 76 patients
      (58%) had sleep apnea as confirmed by an AHI > 10/h. The CPAP trial predicted
      sleep apnea with a sensitivity of 80%, a specificity of 97%, and positive and
      negative predictive values of 97% and 78%, respectively. In 35 of 76 sleep apnea
      patients (46%) with positive CPAP trial results, polysomnography could have been
      avoided. These patients were prescribed long-term CPAP therapy. After 4 months,
      33 of 35 patients (94%) still used CPAP, and their symptoms remained improved.
      These patients were identified by the CPAP trial with positive and negative
      predictive values of 92% and 100%, respectively. CONCLUSIONS: In a selected
      population, a CPAP trial may help to diagnose OSA, to identify patients who
      benefit from CPAP, and to reduce the need for polysomnography.

PMID- 16424415
TI  - Prevalence and correlates of restless legs syndrome: results from the 2005
      National Sleep Foundation Poll.
AB  - PURPOSES: The purpose of this analysis was to investigate the prevalence and
      correlates of restless legs syndrome (RLS) symptoms in the 2005 National Sleep
      Foundation (NSF) Sleep in America 2005 Poll. The NSF poll is an annual telephone
      interview of a random, representative sample of US adults. METHODS: The NSF 2005
      poll included 1,506 adults. Their mean age was 49 years, and 775 were women.
      RESULTS: Symptoms of RLS that included unpleasant feelings in the legs for at
      least a few nights a week, which were worse at night, were reported by 9.7% of
      individuals in this poll, including 8% of men and 11% of women. Those from the
      northeast United States were much less likely to be at risk than those from other
      regions of the country (p < 0.05). Those who were unemployed (p < 0.05) or smoked
      daily (p < 0.5) were more likely to be at risk for RLS, as were those with
      hypertension, arthritis, gastroesophageal reflux disease, depression, anxiety,
      and diabetes (p < 0.05 for all). Adults who were at risk for RLS appeared to also
      be at increased risk for sleep apnea and insomnia (p < 0.05), and were more
      likely to stay up longer than they planned, to take longer than 30 min to fall
      asleep, to drive when drowsy, and to report daytime fatigue than those who were
      not at risk (p < 0.05 for all). They were also more likely to report being late
      to work, missing work, making errors at work, and missing social events because
      of sleepiness than other respondents in the poll (p < 0.05 for all). CONCLUSIONS:
      RLS is significantly associated with medical and psychiatric conditions, other
      sleep disorders, unfavorable lifestyle behaviors, and adverse effects on daytime
      function. Chest physicians who practice sleep medicine need to be able to
      identify and manage RLS, which is prevalent and is associated with considerable
      morbidity.

PMID- 16424416
TI  - Snoring is not relieved by nasal surgery despite improvement in nasal resistance.
AB  - OBJECTIVES: In the present study, we evaluated the effect of nasal surgery on
      snoring time, snoring intensity, and sleep-disordered breathing. The role of
      abnormal cephalometry in treatment outcome was assessed. DESIGN: A cross
      sectional prospective study. SETTING: University teaching hospital. PATIENTS:
      Forty consecutive snoring men who were referred to ENT Hospital because of a
      snoring problem or suspicion of sleep apnea. INTERVENTIONS: The patients
      underwent anterior rhinomanometry and polysomnography (PSG) with recording of
      snoring before and after operative treatment of nasal obstruction. Cephalometric
      radiographs were obtained before surgery. RESULTS: Nasal resistance decreased
      significantly in the overall patient group. Snoring time, snoring intensity,
      nocturnal breathing, and sleep architecture did not change after nasal surgery.
      Cephalometry did not predict operative outcome in these patients. Snoring
      intensity was found to be significantly higher during non-rapid eye movement
      (NREM) sleep than during rapid eye movement sleep. CONCLUSIONS: Operative
      treatment of mainly structural nasal obstruction did not seem to decrease snoring
      intensity, snoring time, or sleep-disordered breathing in an objective assessment
      by PSG performed after surgery. The effect of treating inflammatory nasal changes
      during nocturnal breathing, as well as the role of cephalometry in the prediction
      of treatment outcome will need further evaluation. Higher snoring intensity
      related to NREM sleep may add to the sleep disturbance of a bed partner in the
      evening.

PMID- 16424417
TI  - Creatine phosphokinase elevation in obstructive sleep apnea syndrome: an unknown
      association?
AB  - STUDY OBJECTIVES: To evaluate the impact of obstructive sleep apnea syndrome
      (OSAS) on serum creatine phosphokinase (CK) levels. DESIGN: Single-center
      prospective cross-sectional study. SETTING: Academic sleep disorder center.
      PATIENTS: Two hundred one consecutive patients (mean [+/- SD] age, 54.9 +/- 11.0
      years; 155 men and 46 women; mean body mass index, 31.3 +/- 6.9 kg/m(2)) with
      suspected sleep-disordered breathing. MEASUREMENTS AND RESULTS: OSAS was
      confirmed in182 patients (apnea-hypopnea index [AHI], > 5 events per hour) and
      was ruled out in 19 patients (control subjects) by standard polysomnography.
      Sixty-six OSAS patients and 1 control patient showed an unexplained CK elevation.
      The mean baseline CK level was significantly higher in patients with severe OSAS
      (AHI, > 30 event per hour; n = 89) compared to those with mild-to-moderate OSAS
      (AHI, 5 to 30 events per hour; n = 93) and control subjects (191.4 +/- 12.9 vs
      134.3 +/- 7.5 vs 107.1 +/- 7.9 U/L, respectively; p < 0.01). Receiver operating
      curve analysis identified an optimal cutoff value of > 148 U/L (r = 0.660) for
      CK, which yielded a positive predictive value of 99%, a sensitivity of 43%, and a
      specificity of 95% for the diagnosis of OSAS. The mean nocturnal oxyhemoglobin
      saturation was the main predictor of CK level (r = 0.47; p < 0.001). Continuous
      positive airway pressure (CPAP) treatment resulted in a significant decline of CK
      levels both in patients with mild-to-moderate OSAS (n = 38; 129.7 +/- 13.4 vs
      96.7 +/- 7.6 U/L, respectively; p < 0.001) and in patients with severe OSAS (n =
      39; 187.7 +/- 18.9 vs 132.2 +/- 12.9 U/L, respectively; p < 0.001). CONCLUSIONS:
      One third of our study population showed a mild-to-moderate elevation in CK
      level, which was highly predictive of OSAS. The application of CPAP therapy in
      OSAS patients resulted in a significant decrease in CK level. We speculate that
      OSAS may account for a substantial number of cases of unexplained CK elevation
      (ie, hyperCKemia). Further studies should address the prevalence of OSAS in
      patients with mild-to-moderate hyperCKemia.

PMID- 16424418
TI  - Colonization of severe acute respiratory syndrome-associated coronavirus among
      health-care workers screened by nasopharyngeal swab.
AB  - STUDY OBJECTIVES: To report the efficacy and findings of a large-scale preventive
      screening program for severe acute respiratory syndrome-associated coronavirus
      (SARS-CoV) using amplification of the virus from a nasopharyngeal swab (NPS)
      obtained from the health-care workers (HCWs). DESIGN: A prospective observational
      study. SETTING: A medical center in Taiwan. PARTICIPANTS: Two hundred thirty
      HCWs. INTERVENTION: NPS examination for the presence of SARS-CoV by two nested
      reverse transcription-polymerase chain reaction (RT-PCR) assays. MEASUREMENTS AND
      RESULTS: During the outbreak of severe acute respiratory syndrome (SARS), NPS
      polymerase chain reaction screening of HCWs for SARS-CoV was performed. SARS-CoV
      was examined by two nested RT-PCRs and a quantitative RT-PCR. Serum-specific
      antibodies were assessed by enzyme immunoassay and indirect immunofluorescence.
      We monitored 230 HCWs, including 217 first-line HCWs and 13 non-first-line HCWs.
      One hundred ninety first-line HCWs and 13 non-first-line HCWs had negative
      results in both nested RT-PCR assays. Two first-line HCWs who were positive on
      both nested RT-PCR assays had SARS. They had 16,900 +/- 7,920 copies (mean +/-
      SD) of RNA per milliliter in the NPS and had detectable anti-SARS antibodies. The
      remaining 25 first-line HCWs were negative for the first nested RT-PCR but
      positive for the second nested RT-PCR. Their corresponding titers were 338 +/-
      227 copies of RNA per milliliter; antibodies developed in none of these 25 HCWs.
      The expression and function of angiotensin-converting enzyme-2 were not different
      among these HCWs. This study shows that colonization of SARS-CoV occurred in 25
      of 217 well-protected first-line HCWs on a SARS-associated service, but they
      remained seronegative. CONCLUSION: With the second RT-PCR assay more sensitive
      than the first RT-PCR assay, we are able to show that approximately 11.5% of well
      protected HCWs exposed to SARS patients or specimens may have colonization
      without seroconversion. Only those with significant clinical symptoms or disease
      would have active immunity. Thus, regular NPS screening for nested RT-PCR assays
      in conjunction with a daily recording of body temperature in all first-line HCWs
      may provide an effective way of early detection.

PMID- 16424419
TI  - Fulminant community-acquired Acinetobacter baumannii pneumonia as a distinct
      clinical syndrome.
AB  - STUDY OBJECTIVES: Acinetobacter baumannii (AB) is an important cause of hospital
      acquired pneumonia (HAP), and an uncommon but important cause of community
      acquired pneumonia (CAP) with high mortality. To better characterize CAP-AB, we
      compared its clinical features and outcomes with a control group of HAP-AB
      patients. METHODS: This is a retrospective case-control study comparing CAP-AB
      and HAP-AB patients, which was performed at United Christian Hospital between
      July 2000 and December 2003. RESULTS: There were 19 cases of CAP-AB and 74 cases
      of HAP-AB. When compared with the HAP-AB group, the CAP-AB group had more ever
      smokers (84.3% vs 55.4%, respectively; p = 0.031), more COPD patients (63.2% vs
      29.7%, respectively; p = 0.014), and fewer median days of hospitalization (HAP-AB
      group, median, 0 days; CAP-AB group, 0 days [range, 0 to 30 days]; p = 0.049) in
      the previous year. The CAP-AB group had more patients with positive blood culture
      findings (31.6% vs 0%, respectively; p < 0.001), a higher frequency of ARDS
      (84.2% vs 17.6%, respectively; p < 0.001), and disseminated intravascular
      coagulation (DIC) (57.9% vs 8.1%, respectively; p < 0.001). The median survival
      time was only 8 days in the CAP-AB group, vs 103 days in the HAP-AB group (p =
      0.003). Factors associated with the higher mortality in the CAP-AB group included
      the presence of AB bacteremia (p = 0.040), platelet count of < 120 x 10(9)
      cells/L (p = 0.026), pH < 7.35 on presentation (p = 0.047), and the presence of
      DIC (p = 0.004). CONCLUSIONS: CAP-AB appears to be a unique clinical entity with
      a high incidence of bacteremia, ARDS, DIC, and death, when compared to HAP-AB.
      Further studies are needed to investigate the mechanism of the fulminant nature
      of CAP-AB.

PMID- 16424420
TI  - Candida colonization of the respiratory tract and subsequent pseudomonas
      ventilator-associated pneumonia.
AB  - BACKGROUND: Recovery of Candida from the respiratory tract of a critically ill
      patient receiving mechanical ventilation (MV) usually indicates colonization
      rather than infection of the respiratory tract. However, interactions between
      Candida and bacteria, particularly Pseudomonas, have been reported. Thus, Candida
      colonization of the respiratory tract may predispose to bacterial ventilator
      associated pneumonia (VAP). METHODS: In a multicenter study of immunocompetent
      critically ill patients receiving MV for > 2 days, we compared the incidence of
      pneumonia in patients with and without (exposed/unexposed) respiratory-tract
      Candida colonization, matched on study center, admission year, and MV duration.
      RESULTS: Over the 4-year study period, of the 803 patients meeting study
      inclusion criteria in the six study centers, 214 patients (26.6%) had respiratory
      tract Candida colonization. Candida albicans was the most common species (68.7%),
      followed by Candida glabrata (20.1%) and Candida tropicalis (13.1%).
      Extrapulmonary Candida colonization was more common in exposed patients (39.7% vs
      8.3%, p = 0.01). Exposed patients had longer ICU and hospital stays but similar
      mortality to unexposed patients. The matched exposed/unexposed nested cohort
      study identified bronchial Candida colonization as an independent risk factor for
      pneumonia (24.1% vs 17.6%; adjusted odds ratio [OR], 1.58; 95% confidence
      interval [CI], 0.94 to 2.68; p = 0.0860); the risk increase was greatest for
      Pseudomonas pneumonia (9% vs 4.8%; adjusted OR, 2.22; 95% CI, 1.00 to 4.92; p =
      0.049). CONCLUSIONS: Candida colonization of the respiratory tract is common in
      patients receiving MV for > 2 days and is associated with prolonged ICU and
      hospital stays, and with an increased risk of Pseudomonas VAP.

PMID- 16424421
TI  - Mucus properties in children with primary ciliary dyskinesia: comparison with
      cystic fibrosis.
AB  - OBJECTIVE: It has been assumed that cystic fibrosis (CF) lung disease is due in
      part to abnormal airway mucus. Primary ciliary dyskinesia (PCD) is a form of
      bronchiectasis that is similar to CF in many ways but is caused by congenital
      defects in mucociliary clearance. Our objective was to compare the biophysical
      and transport properties of CF and PCD sputa in subjects matched for age and
      degree of lung function impairment. DESIGN, SETTING, PARTICIPANTS: PCD patients
      (n = 19; mean age, 9.5 +/- 3.0 years [+/- SD]; FEV1, 65.0 +/- 7.8 L) were
      recruited from the clinic at the Royal Brompton Hospital. Patients with CF (n =
      30, mean age, 10.8 +/- 2.6 years; FEV1, 61.8 +/- 22.8 L) were identified from the
      Wake Forest University School of Medicine CF Center. Pulmonary function testing
      and sputum collection were performed as part of routine, scheduled clinic visits.
      MEASUREMENTS: Pulmonary function was measured by spirometry, and sputum was
      collected during the pulmonary function test maneuver. Some patients were
      longitudinally assessed at visits during the course of 3 years. Sputum properties
      measured were dynamic viscoelasticity, wettability, cohesivity, interfacial
      (surface) tension, solids composition, DNA and interleukin (IL)-8 concentration,
      in vitro mucociliary transportability, and cough transportability. RESULTS:
      Inflammation as measured by IL-8 concentration was three times greater in the PCD
      sputa (p < 0.0001). There were no significant differences in the sputum
      biophysical or transport properties comparing CF with PCD sputum. CONCLUSIONS: It
      is unlikely that established CF lung disease is principally due to abnormal
      sputum properties, and it is more likely that the biophysical and transport
      properties reflect disease severity regardless of whether bronchiectasis is due
      to CF or PCD.

PMID- 16424422
TI  - Assessing the effects of racemic and single-enantiomer albuterol on airway
      secretions in long-term intubated patients.
AB  - OBJECTIVE: In vitro data suggest that the S-enantiomer of albuterol can induce
      mucociliary dysfunction. This clinical study assesses the clinical significance
      of standard doses of the S-enantiomer on airway secretions in long-term intubated
      patients by comparing a racemic formulation of albuterol, an R-enantiomer
      formulation, and normal saline solution. DESIGN: A placebo-controlled crossover
      study. PATIENTS: Fourteen stable intubated patients with a median duration of
      intubation of 21 months and a median age of 72 years. SETTING: Long-term
      ventilator unit in skilled nursing facility. INTERVENTIONS: Following a 2-week
      washout period during which regularly scheduled beta2-agonists were discontinued,
      tracheal aspirates were collected for 4 h/d for a 5-day period to establish
      baseline values, and the patients were then randomized in crossover manner to
      each of three nebulized treatments: normal saline solution, racemic albuterol,
      and R-albuterol. Each treatment was administered three times daily for 5 days,
      followed by a 2-day washout. MEASUREMENTS: Tracheal aspirates were analyzed for
      volume, sodium, chloride, bicarbonate, interleukin (IL)-8, IL-1beta, soluble
      intercellular adhesion molecule, and tumor necrosis factor-alpha. RESULTS: There
      were no consistent significant differences among the three treatment periods
      either in terms of volume of secretions or in the concentrations of the
      electrolytes or the inflammatory indexes. However, all three treatments,
      including saline solution, were associated with increased secretion volume after
      the first dose, but this effect was not apparent on subsequent doses. CONCLUSION:
      There were no significant differences between racemic albuterol and R-albuterol
      observed in this study for any of the parameters studied, suggesting that the S
      enantiomer does not adversely affect airway secretions at recommended doses. In
      addition, the routine administration of nebulized beta(2)-sympathomimetic
      agonists to stable patients undergoing prolonged intubation, for the sole purpose
      of changing the volume and composition of secretions of airway secretions, is not
      supported by the results of this study.

PMID- 16424423
TI  - Prolonged invasive ventilation following acute ventilatory failure in COPD:
      weaning results, survival, and the role of noninvasive ventilation.
AB  - BACKGROUND: Invasive ventilation for COPD has significant mortality, and weaning
      can be difficult. At Papworth Hospital, we provide a specialist weaning service
      using noninvasive ventilation (NIV) for patients requiring prolonged invasive
      ventilation after recovery from acute illness. We analyzed our results for
      patients with COPD to identify factors associated with weaning outcome and
      survival. METHODS: A retrospective analysis was conducted of COPD patients
      admitted for weaning from invasive ventilation, from 1992 to 2003. Weaning
      success and survival were assessed. Associations were sought between these
      outcomes and age, sex, spirometry, arterial blood gas levels, APACHE (acute
      physiology and chronic health evaluation) II score, length of stay (LOS), and the
      use of NIV and long-term oxygen therapy. RESULTS: Sixty-seven patients were
      identified, all of whom were receiving tracheostomy ventilation on transfer to
      the Respiratory Support and Sleep Centre (RSSC). Sixty-four patients (95.5%) were
      weaned, and 62 patients survived to hospital discharge. NIV was used in weaning
      40 patients and in the long term in 25 patients. Median survival was 2.5 years
      (interquartile range, 0.7 to 4.6 years). One-year, 2-year, and 5-year survival
      rates were 68%, 54%, and 25%, respectively. Long-term survival was inversely
      associated with age and LOS in the ICU and the RSSC. The provision of maintenance
      NIV after weaning was associated with better long-term survival, independent of
      age and LOS (hazard rate, 0.48; p = 0.03). CONCLUSIONS: These results demonstrate
      that a specialist multidisciplinary approach, including the use of NIV, can be
      successful in weaning most COPD patients from prolonged invasive ventilation. The
      data also suggest that long-term NIV may improve survival in selected patients.

PMID- 16424424
TI  - Osteoporosis in diffuse parenchymal lung disease.
AB  - STUDY OBJECTIVES: There are no studies focused on skeletal status in patients
      with diffuse parenchymal lung disease (DPLD). We hypothesized that patients with
      DPLD referred for lung transplantation would have a high prevalence of
      osteoporosis related to corticosteroid use or reduced pulmonary function and
      exercise capacity. DESIGN: Retrospective cohort study. SETTING: Tertiary care
      center. PATIENTS: Eighty-six patients with DPLD referred to our center for lung
      transplantation evaluation between March 1999 and April 2004. MEASUREMENTS AND
      RESULTS: Dual-energy X-ray absorptiometry was used to measure bone mineral
      density (BMD) at the lumbar spine, femoral neck, total hip, and radius at the
      time of referral. Criteria developed by the World Health Organization were used
      to define osteopenia and osteoporosis. Fifty-five patients (64%) had usual
      interstitial pneumonia-pattern lung disease, 14 patients (16%) had nonspecific
      interstitial pneumonia-pattern lung disease, and 17 patients (20%) had other
      forms of DPLD. Sixty-four patients (74%) were receiving corticosteroids, and 43
      patients (50%) were receiving preventive therapy for osteoporosis. Eleven
      patients (13%; 95% confidence interval [CI], 7 to 22%) met criteria for
      osteoporosis at any site, and 49 patients (57%; 95% CI, 46 to 68%) had
      osteopenia. Lower body mass index (BMI) [adjusted odds ratio (OR), 1.3; 95% CI,
      1.1 to 1.6; p = 0.007] and Hispanic ethnicity (adjusted OR, 9.7; 95% CI, 1.8 to
      52; p = 0.008) were independently associated with an increased risk of
      osteoporosis. Linear regression analysis confirmed that BMD at the femoral neck
      and hip was directly associated with BMI (p < 0.002). These findings were not
      affected by adjustment for the use of corticosteroids or osteoporosis
      prophylaxis, pulmonary function, or exercise performance. CONCLUSIONS: Reduced
      BMD was common in patients with DPLD who were referred for lung transplantation.
      Lower BMD was associated with lower BMI, whereas there was no association with
      other clinical factors in our cohort. Hispanic patients with DPLD had a higher
      risk of osteoporosis than non-Hispanic patients, independent of other variables.
      Given their increased risk of bone loss, patients with DPLD should undergo
      screening for osteoporosis and receive prophylaxis and treatment according to
      published guidelines.

PMID- 16424425
TI  - Endobronchial ultrasound-guided transbronchial lung biopsy in fluoroscopically
      invisible solitary pulmonary nodules: a prospective trial.
AB  - STUDY OBJECTIVES: Transbronchial biopsy (TBBX) for solitary pulmonary nodules
      (SPNs) is usually performed under fluoroscopic guidance, but the diagnostic yield
      depends on lesion size and varies widely. Nodules < 3 cm frequently cannot be
      visualized fluoroscopically. An alternative guidance technique, endobronchial
      ultrasound (EBUS), also allows visualization of pulmonary nodules. This study
      assessed the diagnostic yield of EBUS-guided TBBX in fluoroscopically invisible
      SPNs. DESIGN: The study was a prospective trial using a crossover design.
      PATIENTS AND METHODS: All patients with SPNs and indications for bronchoscopy
      were included in the study. An EBUS-guided examination was performed in patients
      with fluoroscopically invisible nodules. The EBUS probe was introduced through a
      guide catheter into the presumed segment. If a typical ultrasonic picture of
      solid tissue could be seen, the probe was removed and the catheter left in place.
      The biopsy forceps were introduced and specimens taken. RESULTS: One hundred
      thirty-eight consecutive patients with SPNs were examined. Of those, 54 patients
      presented with SPNs that could not be visualized with fluoroscopy. The mean
      diameter of the nodules was 2.2 cm. In 48 patients (89%), the lesion was
      localized with EBUS, and in 38 patients (70%) the biopsy established the
      diagnosis. The 16 patients with undiagnosed SPNs were referred for surgical
      biopsy; 10 of those lesions were malignant and 6 were benign. The diagnosis in
      nine patients (17%) saved the patients from having to undergo a surgical
      procedure. The only complication was a pneumothorax in one patient. CONCLUSIONS:
      EBUS-guided TBBX is a safe and very effective method for SPNs that cannot be
      visualized by fluoroscopy. The procedure may increase the yield of endoscopic
      biopsy in patients with these nodules and avert the need for surgical procedures.

PMID- 16424426
TI  - Reduced histone deacetylase in COPD: clinical implications.
AB  - COPD is characterized by progressive inflammation in the small airways and lung
      parenchyma, and this is mediated by the increased expression of multiple
      inflammatory genes. The increased expression of inflammatory genes is regulated
      by acetylation of core histones around which DNA is wound, and conversely these
      activated genes are switched off by deacetylation of these histones. Histone
      deacetylases (HDACs) suppress inflammatory gene expression, but their activity
      and expression (particularly of HDAC-2) is reduced in the peripheral lung and in
      alveolar macrophages of patients with COPD. This results in amplification of the
      inflammatory response as COPD progresses but also accounts for corticosteroid
      resistance in COPD, since HDAC-2 is required by corticosteroids to switch off
      activated inflammatory genes. The reduction in HDAC-2 appears to be secondary to
      the increased oxidative and nitrative stress in COPD lungs. Antioxidants and
      inhibitors of nitric oxide synthesis may therefore restore corticosteroid
      sensitivity in COPD, but this can also be achieved by low doses of theophylline,
      which is an HDAC activator. This mechanism is also relevant to asthmatic patients
      who smoke, patients with severe asthma and cystic fibrosis, in whom oxidative
      stress is also increased.

PMID- 16424427
TI  - Avian influenza virus infections in humans.
AB  - Seroepidemiologic and virologic studies since 1889 suggested that human influenza
      pandemics were caused by H1, H2, and H3 subtypes of influenza A viruses. If not
      for the 1997 avian A/H5N1 outbreak in Hong Kong of China, subtype H2 is the
      likely candidate for the next pandemic. However, unlike previous poultry
      outbreaks of highly pathogenic avian influenza due to H5 that were controlled by
      depopulation with or without vaccination, the presently circulating A/H5N1
      genotype Z virus has since been spreading from Southern China to other parts of
      the world. Migratory birds and, less likely, bird trafficking are believed to be
      globalizing the avian influenza A/H5N1 epidemic in poultry. More than 200 human
      cases of avian influenza virus infection due to A/H5, A/H7, and A/H9 subtypes
      mainly as a result of poultry-to-human transmission have been reported with a >
      50% case fatality rate for A/H5N1 infections. A mutant or reassortant virus
      capable of efficient human-to-human transmission could trigger another influenza
      pandemic. The recent isolation of this virus in extrapulmonary sites of human
      diseases suggests that the high fatality of this infection may be more than just
      the result of a cytokine storm triggered by the pulmonary disease. The emergence
      of resistance to adamantanes (amantadine and rimantadine) and recently
      oseltamivir while H5N1 vaccines are still at the developmental stage of phase I
      clinical trial are causes for grave concern. Moreover, the to-be pandemic strain
      may have little cross immunogenicity to the presently tested vaccine strain. The
      relative importance and usefulness of airborne, droplet, or contact precautions
      in infection control are still uncertain. Laboratory-acquired avian influenza
      H7N7 has been reported, and the laboratory strains of human influenza H2N2 could
      also be the cause of another pandemic. The control of this impending disaster
      requires more research in addition to national and international preparedness at
      various levels. The epidemiology, virology, clinical features, laboratory
      diagnosis, management, and hospital infection control measures are reviewed from
      a clinical perspective.

PMID- 16424428
TI  - Pulmonary rehabilitation and respiratory therapy services in the physician office
      setting.
AB  - Pulmonary rehabilitation services benefit patients with chronic lung disease by
      reducing symptoms and restoring independent function. With a multidisciplinary
      approach to individual patient care through education, exercise, and psychosocial
      interventions, health-care costs and utilization may be reduced. While pulmonary
      rehabilitation services have typically been provided in a facility setting, many
      respiratory care services can be safely provided and appropriately reimbursed in
      the outpatient physician office setting, with appropriate physician supervision.
      After reviewing the utility of pulmonary rehabilitation for patients with chronic
      lung disease, the supervision, documentation, coding, and reimbursement
      requirements for providing rehabilitative respiratory care services in the
      outpatient office setting are detailed.

PMID- 16424429
TI  - Grading strength of recommendations and quality of evidence in clinical
      guidelines: report from an american college of chest physicians task force.
AB  - While grading the strength of recommendations and the quality of underlying
      evidence enhances the usefulness of clinical guidelines, the profusion of
      guideline grading systems undermines the value of the grading exercise. An
      American College of Chest Physicians (ACCP) task force formulated the criteria
      for a grading system to be utilized in all ACCP guidelines that included
      simplicity and transparency, explicitness of methodology, and consistency with
      current methodological approaches to the grading process. The working group
      examined currently available systems, and ultimately modified an approach
      formulated by the international GRADE group. The grading scheme classifies
      recommendations as strong (grade 1) or weak (grade 2), according to the balance
      among benefits, risks, burdens, and possibly cost, and the degree of confidence
      in estimates of benefits, risks, and burdens. The system classifies quality of
      evidence as high (grade A), moderate (grade B), or low (grade C) according to
      factors that include the study design, the consistency of the results, and the
      directness of the evidence. For all future ACCP guidelines, The College has
      adopted a simple, transparent approach to grading recommendations that is
      consistent with current developments in the field. The trend toward uniformity of
      approaches to grading will enhance the usefulness of practice guidelines for
      clinicians.

PMID- 16424430
TI  - Addressing resource allocation issues in recommendations from clinical practice
      guideline panels: suggestions from an American College of Chest Physicians task
      force.
AB  - Most panels that develop clinical practice guidelines are poorly equipped to
      address resource allocation or cost issues associated with management options.
      This risks neglect, arbitrariness, lack of transparency, and methodological flaws
      in consideration of resource allocation. We provide recommendations for guideline
      panels to promote greater transparency and rigor. We suggest focusing on resource
      allocation issues for only a limited number of recommendations and provide
      criteria for selecting those in which economic considerations are likely to
      influence the direction or strength of the recommendation. Panels should involve
      a health economist to assist with the systematic review and critical
      interpretation of relevant economic analyses. They should carefully define the
      intended audience and may consider issuing alternative recommendations when
      available resources vary widely across target clinical settings. Targeting a
      limited number of recommendations for the consideration of resource allocation
      issues, and ensuring methodologically high-quality review, will best serve
      guideline panels, and the health-care providers and patients they hope to assist.

PMID- 16424431
TI  - Performance measures and pay for performance.
AB  - Performance measures and pay for performance are terms creating considerable
      angst among physicians today. Understanding the driving forces behind these
      concepts will help practitioners to strategically plan for their impact on
      individual physician practices and on health care in general. Medical societies
      can play a vital role in assisting physicians in the identification of
      appropriate performance measures used to gauge physician practices and by
      supporting efforts to develop equitable principles driving reimbursement based on
      adherence to those measures. Performance measures and pay for performance are
      terms evoking considerable angst across all sectors of the health services
      industry.

PMID- 16424432
TI  - Resolution of thromboemboli in patients with acute pulmonary embolism: a
      systematic review.
AB  - STUDY OBJECTIVES: Much attention has been paid in recent years to optimizing the
      diagnosis of acute pulmonary embolism (PE). However, little is known about the
      changes in clot burden that occur at the level of the pulmonary arteries after
      documented PE. It is often problematic to distinguish between a new or residual
      defect on lung scintigraphy or helical CT. This may lead to falsely labeling
      patients with residual PE as having recurrent PE and consequent unnecessary
      treatment changes. DESIGN: We performed a systematic analysis of studies of
      imaging tests (radionuclide and CT) evaluating resolution rate of PE with
      independent assessment of predefined methodologic criteria by two investigators.
      RESULTS: We identified 29 clinical studies. Of these, 25 studies were excluded
      and 4 studies were included in our review. Because studies differed largely in
      patient selection, duration of anticoagulation, and timing of follow-up, the
      studies were not pooled but briefly described. The percentage of patients with
      residual pulmonary thrombi was 87% at 8 days after diagnosis, 68% after 6 weeks,
      65% after 3 months, 57% after 6 months, and 52% after 11 months. DISCUSSION: This
      review shows that complete resolution of PE is not routinely achieved between 8
      days and 11 months after diagnosis. More than 50% of patients with PE still have
      defects 6 months after diagnosis, after which resolution of thrombi appears to
      reach a plateau phase. Physicians should be aware of the high percentage of
      incomplete resolution of pulmonary emboli. Routine re-imaging after cessation of
      anticoagulant therapy in patients with PE to obtain a new baseline could be
      considered.

PMID- 16424433
TI  - Unrecognized sleep apnea in the surgical patient: implications for the
      perioperative setting.
AB  - Anesthesia and surgery both affect the architecture of sleep. Aside from the
      postoperative effects of anesthesia and surgery, sleep deprivation and
      fragmentation have been shown to produce apneas or desaturations even in patients
      without presumed sleep apnea. Recent epidemiologic data have placed the
      prevalence of obstructive sleep apnea syndrome (OSAS) at about 5% among Western
      countries. The problem is further hindered by the difficulty in diagnosing OSAS,
      as patients with OSAS may present for surgery without a prior diagnosis. Clinical
      suspicion for OSAS may first be recognized intraoperatively. Adverse surgical
      outcomes appear to be more frequent in OSAS patients. Immediate postoperative
      complications may intuitively be attributed to the negative effects of sedative,
      analgesic, and anesthetic agents, which can worsen OSAS by decreasing pharyngeal
      tone, and the arousal responses to hypoxia, hypercarbia, and obstruction. Later
      events are, however, more likely to be related to postoperative rapid eye
      movement (REM) sleep rebound. In the severe OSAS patient, REM sleep rebound could
      conceivably act in conjunction with opioid administration and supine posture to
      aggravate sleep-disordered breathing. REM sleep rebound has also been suggested
      to contribute to mental confusion and postoperative delirium, myocardial
      ischemia/infarction, stroke, and wound breakdown. Although the data to guide the
      perioperative management of patients with moderate-to-severe OSAS is scarce,
      heightened awareness is recommended. The selected use of therapy with nasal
      continuous positive airway pressure before surgery and after extubation may be
      beneficial. LEARNING OBJECTIVES: 1. Identify common sleep architectures affected
      by anesthesia and surgery in the perioperative period. 2. State a perioperative
      complication in Obstructive Sleep Apnea Syndrome patients. 3. Identify
      perioperative interventions and management techniques that best facilitate
      improved obstructive sleep apnea syndrome patient care.

PMID- 16424434
TI  - A 47-year-old man with common-variable immunodeficiency and chronic cough.

PMID- 16424435
TI  - Permissive hypoxemia: is it time to change our approach?

PMID- 16424436
TI  - On depression, antidepressant medications, and resuscitation preferences in COPD
      patients.

PMID- 16424437
TI  - Plasma levels of N-terminal pro-brain natriuretic peptide in the critically ill:
      the right hormonal marker in the wrong patients?

PMID- 16424438
TI  - Mechanism of mucin secretion in diffuse panbronchiolitis.

PMID- 16424439
TI  - Idiopathic chronic cough and organ-specific autoimmune disease.

PMID- 16424440
TI  - Is SNAP technology accurate in the diagnosis of obstructive sleep apnea?

PMID- 16424441
TI  - Risk taking, depression, adherence, and symptom control in adolescents and young
      adults with asthma.
AB  - Risk behaviors, including tobacco, alcohol, and drug use, are common in
      adolescents and young adults. Those who engage in one risk behavior are likely to
      engage in additional health risk behaviors, and as the number of risk behaviors
      increase, depression comorbidity emerges. For young people with chronic illness,
      risk behavior and depression are also common. There is some evidence that both
      depression and risk behavior are associated with nonadherence to medications,
      poor treatment outcomes, and death. The relationship between depression and
      asthma may involve more than one causal pathway and includes the possibility that
      depression can lead to a sense of hopelessness that erodes adherence and other
      health-promoting behavior, or that depression impacts asthma directly by altering
      the immune system. An assessment of the interplay between risk behavior,
      depression, adherence, and asthma can add important new information to our
      understanding about how to identify and treat those at greatest risk for poorly
      controlled disease and asthma-related death. New behavioral studies must overcome
      the shortcomings frequently seen in previous research and include well-designed
      and controlled investigations using valid behavioral measures of risk behavior,
      mood disorder, and adherence; recruitment that includes sufficient numbers of
      subjects and gives careful consideration of selection bias; and employment of
      multivariate data modeling to allow for simultaneous statistical examination of
      multiple relationships.

PMID- 16424442
TI  - The scope and impact of treatment of latent tuberculosis infection in the United
      States and Canada.
AB  - RATIONALE: The scope of treatment of latent tuberculosis infection (LTBI) in the
      United States and Canada is unknown. Identifying the types of clinics that
      administer such treatment and patients who receive it could guide resource
      utilization and improve treatment initiation and completion. OBJECTIVES: Estimate
      the number of persons started on LTBI treatment; describe the types of clinics
      that treat LTBI. METHODS: The Tuberculosis Epidemiologic Studies Consortium,
      consisting of 19 United States and 2 Canadian sites, conducted a survey among
      clinics that initiated LTBI treatment for>or=10 patients in 2002. RESULTS: Study
      catchment areas from the 19 United States sites represented 8.6% of the United
      States population and 12.7% of all tuberculosis cases in 2000. An estimated
      37,857 patients started LTBI treatment during 2002 at 244 clinics surveyed. Of
      these treatment starts, 29,970 (79%) occurred at general public health clinics;
      immigrant/refugee clinics (2,409; 6.4%) and correctional/detention facilities
      (2,325; 6.1%) were the next most common sites. Based on these data, United States
      tuberculosis case rates, and United States population data, the estimated total
      number of LTBI treatment starts in the United States was 291,000-433,000. When
      the 37,145 persons who initiated LTBI treatment in the United States were
      extrapolated to the entire United States population, with a 5% lifetime risk of
      tuberculosis without treatment, and 20-60% treatment effectiveness, approximately
      4,000-11,000 tuberculosis cases were prevented in the United States. CONCLUSIONS:
      LTBI treatment is initiated among a substantial number of persons in the United
      States and Canada, primarily in the public sector. Treatment of LTBI can
      significantly decrease the tuberculosis burden.

PMID- 16424443
TI  - Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep
      Heart Health Study.
AB  - RATIONALE: Sleep-disordered breathing recurrent intermittent hypoxia and
      sympathetic nervous system activity surges provide the milieu for cardiac
      arrhythmia development. OBJECTIVE: We postulate that the prevalence of nocturnal
      cardiac arrhythmias is higher among subjects with than without sleep-disordered
      breathing. METHODS: The prevalence of arrhythmias was compared in two samples of
      participants from the Sleep Heart Health Study frequency-matched on age, sex,
      race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered
      breathing (respiratory disturbance index>or=30) and (2) 338 subjects without
      sleep-disordered breathing (respiratory disturbance index<5). RESULTS: Atrial
      fibrillation, nonsustained ventricular tachycardia, and complex ventricular
      ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or
      quadrigeminy) were more common in subjects with sleep-disordered breathing
      compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003)
      for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular
      tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared
      with those without sleep-disordered breathing and adjusting for age, sex, body
      mass index, and prevalent coronary heart disease, individuals with sleep
      disordered breathing had four times the odds of atrial fibrillation (odds ratio
      [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of
      nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost
      twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A
      significant relation was also observed between sleep-disordered breathing and
      ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome.
      CONCLUSIONS: Individuals with severe sleep-disordered breathing have two- to
      fourfold higher odds of complex arrhythmias than those without sleep-disordered
      breathing even after adjustment for potential confounders.

PMID- 16424444
TI  - Antiinflammatory effects of salmeterol/fluticasone propionate in chronic
      obstructive lung disease.
AB  - RATIONALE: No currently available treatment is reported to reduce the exaggerated
      airway wall inflammation of chronic obstructive pulmonary disease. OBJECTIVES: We
      tested the hypothesis that inhaled combined long-acting beta2-agonist
      (salmeterol) and corticosteroid (fluticasone propionate) will reduce
      inflammation. METHODS: Bronchial biopsies and induced sputum were taken from 140
      current and former smokers (mean age, 64 yr) with moderate to severe disease,
      randomized in a 13-wk double-blind study to placebo (n = 73) or
      salmeterol/fluticasone propionate 50/500 microg (n = 67) twice daily. Biopsies
      were repeated at 12 wk and sputa at 8 and 13 wk. After adjustment for
      multiplicity, comparisons between active and placebo were made for median change
      from baseline in the numbers of biopsy CD8+ and CD68+ cells/mm2 and sputum
      neutrophils. MEASUREMENTS AND MAIN RESULTS: Combination therapy was associated
      with a reduction in biopsy CD8+ cells of -118 cells/mm2 (95% confidence interval
      [CI], -209 to -42; p = 0.02), a reduction of 36% over placebo (p = 0.001). CD68+
      cells were unaffected by combination treatment. Sputum differential (but not
      total) neutrophils reduced progressively and, at Week 13, significantly with
      combination treatment (median treatment difference, 8.5%; 95% CI, 1.75%-15.25%; p
      = 0.04). The combination also significantly reduced biopsy CD45+ and CD4+ cells
      and cells expressing genes for tumor necrosis factor-alpha and IFN-gamma and
      sputum total eosinophils (all p < or = 0.03). These antiinflammatory effects were
      accompanied by a 173-ml (95% CI, 104-242; p < 0.001) improvement in
      prebronchodilator FEV1. CONCLUSIONS: The combination of salmeterol and
      fluticasone propionate has a broad spectrum of antiinflammatory effects in both
      current and former smokers with chronic obstructive pulmonary disease, which may
      contribute to clinical efficacy.

PMID- 16424445
TI  - Calcineurin regulates myocardial function during acute endotoxemia.
AB  - RATIONALE: Cyclosporin A (CsA) is known to preserve cardiac contractile function
      during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO)
      production and altered mitochondrial function are implicated as mechanisms
      contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to
      reduce NO production and inhibit mitochondrial dysfunction relating to the
      mitochondrial permeability transition (MPT). OBJECTIVES: We hypothesized that CsA
      would protect against endotoxin-mediated cardiac contractile dysfunction by
      attenuating NO production and preserving mitochondrial function. METHODS: Left
      ventricular function was measured continuously over 4 h in cats assigned as
      follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n
      = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1
      mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min
      by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue
      nitration, protein carbonylation, and mitochondrial morphology and function.
      MEASUREMENTS AND MAIN RESULTS: LPS treatment resulted in impaired left
      ventricular contractility, altered mitochondrial morphology and function, and
      increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac
      performance and mitochondrial respiration and reduced myocardial protein
      nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both
      cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments
      markedly increased protein carbonylation in the myocardium despite elevated
      manganese superoxide dismutase activity during endotoxemia. CONCLUSIONS: Our data
      indicate that calcineurin is a critical regulator of mitochondrial respiration,
      tissue nitration, protein carbonylation, and contractile function in the heart
      during acute endotoxemia.

PMID- 16424446
TI  - Transtracheal open ventilation in acute respiratory failure secondary to severe
      chronic obstructive pulmonary disease exacerbation.
AB  - RATIONALE: Patients who fail noninvasive ventilation are generally intubated and
      are then subjected to complications of invasive mechanical ventilation. With
      transtracheal open ventilation, ventilator support is delivered through an
      uncuffed small bore minitracheostomy tube, which eliminates pooling of secretions
      above the cuff and thus reduces the risk of tracheobronchial microbial
      colonization. OBJECTIVE: To compare transtracheal open ventilation (treatment
      group) with conventional invasive ventilation (control group) in patients with
      exacerbation of chronic obstructive pulmonary disease who initially failed
      noninvasive ventilation. METHODS: Patients were randomized to receive trans
      tracheal open ventilation (n=19) or conventional invasive ventilation (n=20).
      MEASUREMENTS AND MAIN RESULTS: There was no difference in arterial blood gases
      after 1 and 30 h between the two groups. Two patients receiving transtracheal
      open ventilation and 13 undergoing conventional ventilation had complications
      (p<0.0001). Compared with conventional ventilation, transtracheal open
      ventilation significantly decreased both the duration of mechanical ventilation
      (7.6+/-4.7 vs. 18.6+/-10.6 d, p<0.0001) and length of stay in the intensive care
      unit (10.2+/-4.5 vs. 21.3+/-9.7 d, p<0.0001). CONCLUSIONS: Transtracheal open
      ventilation was as effective as conventional ventilation in maintaining adequate
      gas exchange and reducing complications, duration of mechanical ventilation, and
      intensive care unit length of stay.

PMID- 16424447
TI  - Reduction in fine particulate air pollution and mortality: Extended follow-up of
      the Harvard Six Cities study.
AB  - RATIONALE: A large body of epidemiologic literature has found an association of
      increased fine particulate air pollution (PM2.5) with acute and chronic
      mortality. The effect of improvements in particle exposure is less clear.
      OBJECTIVES: Earlier analysis of the Harvard Six Cities adult cohort study showed
      an association between long-term ambient PM2.5 and mortality between enrollment
      in the mid-1970s and follow-up until 1990. We extended mortality follow-up for 8
      yr in a period of reduced air pollution concentrations. METHODS: Annual city
      specific PM2.5 concentrations were measured between 1979 and 1988, and estimated
      for later years from publicly available data. Exposure was defined as (1) city
      specific mean PM2.5 during the two follow-up periods, (2) mean PM2.5 in the first
      period and change between these periods, (3) overall mean PM2.5 across the entire
      follow-up, and (4) year-specific mean PM2.5. Mortality rate ratios were estimated
      with Cox proportional hazards regression controlling for individual risk factors.
      MEASUREMENTS AND MAIN RESULTS: We found an increase in overall mortality
      associated with each 10 microg/m3 increase in PM2.5 modeled either as the overall
      mean (rate ratio [RR], 1.16; 95% confidence interval [CI], 1.07-1.26) or as
      exposure in the year of death (RR, 1.14; 95% CI, 1.06-1.22). PM2.5 exposure was
      associated with lung cancer (RR, 1.27; 95% CI, 0.96-1.69) and cardiovascular
      deaths (RR, 1.28; 95% CI, 1.13-1.44). Improved overall mortality was associated
      with decreased mean PM2.5 (10 microg/m3) between periods (RR, 0.73; 95% CI, 0.57
      0.95). CONCLUSION: Total, cardiovascular, and lung cancer mortality were each
      positively associated with ambient PM2.5 concentrations. Reduced PM2.5
      concentrations were associated with reduced mortality risk.

PMID- 16424448
TI  - Basal ganglia orient eyes to reward.
AB  - Expectation of reward motivates our behaviors and influences our decisions.
      Indeed, neuronal activity in many brain areas is modulated by expected reward.
      However, it is still unclear where and how the reward-dependent modulation of
      neuronal activity occurs and how the reward-modulated signal is transformed into
      motor outputs. Recent studies suggest an important role of the basal ganglia.
      Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly
      modulated by expected reward. Through their abundant outputs to the brain stem
      motor areas and the thalamocortical circuits, the basal ganglia appear capable of
      producing body movements based on expected reward. A good behavioral measure to
      test this hypothesis is saccadic eye movement because its brain stem mechanism
      has been extensively studied. Studies from our laboratory suggest that the basal
      ganglia play a key role in guiding the gaze to the location where reward is
      available. Neurons in the caudate nucleus and the substantia nigra pars
      reticulata are extremely sensitive to the positional difference in expected
      reward, which leads to a bias in excitability between the superior colliculi such
      that the saccade to the to-be-rewarded position occurs more quickly. It is
      suggested that the reward modulation occurs in the caudate where cortical inputs
      carrying spatial signals and dopaminergic inputs carrying reward-related signals
      are integrated. These data support a specific form of reinforcement learning
      theories, but also suggest further refinement of the theory.

PMID- 16424449
TI  - Queer currents, steady rhythms, and drunken da neurons. Focus on
      "hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain
      dopamine neurons of mice".

PMID- 16424450
TI  - Specificity of cone connections in the retina and color vision. Focus on
      "specificity of cone inputs to macaque retinal ganglion cells".

PMID- 16424451
TI  - The beat goes on, and up and down. Focus on "bursts of information: coordinating
      interneurons encode multiple parameters of a periodic motor pattern".

PMID- 16424452
TI  - Textures of natural images in the human brain. Focus on "orientation-selective
      adaptation to first- and second-order patterns in human visual cortex".

PMID- 16424453
TI  - Contribution of feedback and feedforward strategies to locomotor adaptations.
AB  - The aim of this study was to examine the strategies used by human subjects to
      adapt their walking pattern to a velocity-dependent resistance applied against
      hip and knee movements. Subjects first walked on a treadmill with their lower
      limbs strapped to an exoskeletal robotic gait orthosis with no resistance against
      leg motions (null condition). Afterward, a velocity-dependent resistance was
      applied against left hip and knee movements (force condition). Catch trials were
      interspersed throughout the experiment to track the development of adaptive
      changes in the walking pattern. After 188 steps in the force condition, subjects
      continued to step in the null condition for another 100 steps (washout period).
      Leg muscle activity and joint kinematics were recorded and analyzed. The adaptive
      modifications in the locomotor pattern suggest the involvement of both feedback
      and feedforward control strategies. Feedback-driven adaptations were reflected in
      increases in rectus femoris and tibialis anterior activity during swing, which
      occurred immediately, only in the presence of resistance, and not during the
      catch trials. Locomotor adaptations involving feedforward strategies were
      reflected in enhanced pre-swing activity in the biceps femoris and medial
      hamstrings muscles, which required experience and persisted in the catch trials.
      During washout subjects showed a gradual deadaptation of locomotor activity to
      control levels. In summary, adaptive changes in the walking pattern were driven
      by both feedback and feedforward adjustments in the walking pattern appropriate
      for overcoming the effects of resistance.

PMID- 16424454
TI  - Comparison of midbrain and thalamic space-specific neurons in barn owls.
AB  - Spatial receptive fields of neurons in the auditory pathway of the barn owl
      result from the sensitivity to combinations of interaural time (ITD) and level
      differences across stimulus frequency. Both the forebrain and tectum of the owl
      contain such neurons. The neural pathways, which lead to the forebrain and tectal
      representations of auditory space, separate before the midbrain map of auditory
      space is synthesized. The first nuclei that belong exclusively to either the
      forebrain or the tectal pathways are the nucleus ovoidalis (Ov) and the external
      nucleus of the inferior colliculus (ICx), respectively. Both receive projections
      from the lateral shell subdivision of the inferior colliculus but are not
      interconnected. Previous studies indicate that the owl's tectal representation of
      auditory space is different from those found in the owl's forebrain and the
      mammalian brain. We addressed the question of whether the computation of spatial
      cues in both pathways is the same by comparing the ITD tuning of Ov and ICx
      neurons. Unlike in ICx, the relationship between frequency and ITD tuning had not
      been studied in single Ov units. In contrast to the conspicuous frequency
      independent ITD tuning of space-specific neurons of ICx, ITD selectivity varied
      with frequency in Ov. We also observed that the spatially tuned neurons of Ov
      respond to lower frequencies and are more broadly tuned to ITD than in ICx. Thus
      there are differences in the integration of frequency and ITD in the two sound
      localization pathways. Thalamic neurons integrate spatial information not only
      within a broader frequency band but also across ITD channels.

PMID- 16424456
TI  - Effects of a chronic compression of the dorsal root ganglion on voltage-gated Na+
      and K+ currents in cutaneous afferent neurons.
AB  - A chronic compression of the dorsal root ganglion (CCD) produces ipsilateral
      cutaneous hyperalgesia that is associated with an increased excitability of
      neuronal somata in the compressed ganglion, as evidenced by spontaneous activity
      and a lower rheobase. We searched for differences in the properties of voltage
      gated Na+ and K+ currents between somata of CCD- and control (unoperated) rats.
      CCD was produced in adult rats by inserting two rods through the intervertebral
      foramina, one compressing the L4, and the other, the ipsilateral, L5 dorsal root
      ganglion (DRG). After 5-9 days, DRG somata were dissociated and placed in culture
      for 16-26 h. Cutaneous neurons of medium size (35-45 microm), Fluorogold-labeled
      from the hindpaw, were selected for whole cell patch-clamp recording of action
      potentials and ion currents. In comparison with control neurons, CCD neurons had
      steady-state activation curves for TTX-sensitive (TTX-S) Na+ currents that were
      shifted in the hyperpolarizing direction, and CCD neurons had enhanced TTX
      resistant (TTX-R) current. CCD neurons also had smaller, fast-inactivating K+
      currents (Ka) at voltages from -30 to 50 mV. The reduction in Ka, the
      hyperpolarizing shift in TTX-S Na+ current activation, and the enhanced TTX-R Na+
      current may all contribute to the enhanced neuronal excitability and thus to the
      pain and hyperalgesia associated with CCD.

PMID- 16424455
TI  - Specificity of cone inputs to macaque retinal ganglion cells.
AB  - The specificity of cone inputs to ganglion cells has implications for the
      development of retinal connections and the nature of information transmitted to
      higher areas of the brain. We introduce a rapid and precise method for measuring
      signs and magnitudes of cone inputs to visual neurons. Colors of stimuli are
      modulated around circumferences of three color planes in clockwise and
      counterclockwise directions. For each neuron, the projection of the preferred
      vector in each plane was estimated by averaging the response phases to clockwise
      and counterclockwise modulation. The signs and weights of cone inputs were
      derived directly from the preferred vectors. The efficiency of the method enables
      us to measure cone inputs at different temporal frequencies and short-wavelength
      sensitive (S) cone adaptation levels. The results show that S-cone inputs to the
      parvocellular and magnocellular ganglion cells are negligible, which implies
      underlying connectional specificity in the retinal circuitry.

PMID- 16424457
TI  - Synaptic interactions underlying song-selectivity in the avian nucleus HVC
      revealed by dual intracellular recordings.
AB  - Stimulus-dependent synaptic interactions underlying selective sensory
      representations in neural circuits specialized for sensory processing and
      sensorimotor integration remain poorly understood. The songbird telencephalic
      nucleus HVC is a sensorimotor area essential to learned vocal control with one
      projection neuron (PN) type (HVC(RA)) innervating a song premotor pathway,
      another PN (HVC(X)) innervating a basal ganglia pathway essential to vocal
      plasticity, and interneurons (HVC(Int)). Playback of the bird's own song (BOS),
      but not other songs, evokes action potential bursts from both PNs, but HVC(RA)
      and HVC(X) display distinct BOS-evoked subthreshold responses. To characterize
      synaptic interactions underlying HVC's BOS-selective responses and assess
      stimulus-evoked changes in functional interactions between HVC neurons, we made
      simultaneous in vivo intracellular recordings from various HVC neuron pairs in
      urethan-anesthetized zebra finches. Spike-triggered averaging revealed that all
      HVC neuron types receive common excitation and that the onset of this excitation
      occurs during a narrower time window in projection neurons during BOS playback.
      To distinguish local from extrinsic contributions to HVC subthreshold response
      patterns, we inactivated the HVC local circuit with GABA or occluded inhibition
      in single HVC(X) cells. After either treatment, BOS-evoked responses in HVC(X)
      neurons became purely depolarizing and subthreshold responses of HVC(X) and
      HVC(RA) cells became remarkably similar to one another while retaining BOS
      selectivity. Therefore both PN types receive a common extrinsic source of BOS
      selective excitation, and local inhibition specifically alters processing of
      auditory information in HVC(X) cells. In HVC, excitatory and inhibitory synaptic
      interactions are recruited in a stimulus-dependent fashion, affecting auditory
      representations of the BOS locally and in other song nuclei important to song
      learning and production.

PMID- 16424458
TI  - Cortico-cerebellar coherence during a precision grip task in the monkey.
AB  - We studied the synchronization of single units in macaque deep cerebellar nuclei
      (DCN) with local field potentials (LFPs) in primary motor cortex (M1) bilaterally
      during performance of a precision grip task. Analysis was restricted to periods
      of steady holding, during which M1 oscillations are known to be strongest.
      Significant coherence between DCN units and M1 LFP oscillations bilaterally was
      seen at approximately 10-40 Hz (contralateral M1: 25/87 units; ipsilateral: 9/87
      units). Averaged coherence between DCN units and contralateral M1 LFP showed a
      prominent approximately 17-Hz coherence peak and an average phase of
      approximately -pi/2 radians, implying that the DCN units fired around the time of
      maximal depolarization of M1 cells. The lack of a time delay between DCN and M1
      activity suggests that the cerebellum and cortex may form a pair of phase coupled
      oscillators. Although coherence values were low (mean peak coherence, 0.018), we
      used a computational model to show that this probably resulted from the
      nonlinearity of spike generating mechanisms within the DCN. DCN unit discharge
      and DCN LFPs also showed significant coherence at approximately 10-40 Hz, with
      similarly low magnitude (mean peak coherence, 0.012). The average coherence phase
      was -2.5 radians for the 6- to 14-Hz range and -1.1 radians for the 17- to 41-Hz
      range, suggesting different frequency-specific underlying mechanisms. Finally,
      4/40 pairs of simultaneously recorded DCN units showed a significant cross
      correlation peak, and 16/40 pairs showed significant unit-unit coherence. The
      extensive oscillatory synchronization observed between cerebellum and motor
      cortex may have functional importance in sensorimotor processing.

PMID- 16424459
TI  - Chemical and cold sensitivity of two distinct populations of TRPM8-expressing
      somatosensory neurons.
AB  - The cold- and menthol-sensing TRPM8 receptor has been proposed to have both
      nonnociceptive and nociceptive functions. However, one puzzle is how this single
      type of receptor may be used by somatosensory neurons to code for two distinct
      sensory modalities. Using acutely dissociated rat dorsal root ganglion (DRG)
      neurons without culture, we show that TRPM8 receptors are expressed on two
      distinct classes of somatosensory neurons. One class is sensitive to menthol and
      features nonnociceptive neuron properties, including capsaicin-insensitive, ATP
      insensitive, transient acid response, and expression of TTX-sensitive sodium
      channels only. This class is termed the menthol-sensitive/capsaicin-insensitive
      neuron class (MS/CIS). The other class is also sensitive to menthol but has
      characteristics of nociceptive neurons including capsaicin-sensitive, ATP
      sensitive, prolonged acid response, and expression of both TTX-sensitive and TTX
      resistant sodium channels. This class is termed the menthol-sensitive/capsaicin
      sensitive neuron class (MS/CS). The presence of these two neuron classes in
      acutely dissociated DRG neurons support the idea that TRPM8 receptors can have
      both nonnociceptive and nociceptive functions. While both neuron classes respond
      to menthol and cold, the overall responses induced by menthol and cold are
      significantly larger in MS/CIS than in MS/CS neurons. Furthermore, low
      concentrations of menthol produce strong selection of the MS/CIS neuron
      population over the MS/CS neuron population. On the other hand, the population
      selection becomes weaker with higher concentrations of menthol. TRPM8 current
      density shows significant higher in MS/CIS neurons than in MS/CS neurons,
      suggesting different expression levels of TRPM8 receptors between the two neuron
      populations, and this difference may provide a mean of selective activation of
      MS/CIS neurons at low stimulation intensity.

PMID- 16424460
TI  - Developing professionalism of osteopathic trainees through mentorship: KCOM's
      "Societies" model.

PMID- 16424461
TI  - Ripple effects of terrorism.

PMID- 16424463
TI  - Osteopathic manipulative treatment of somatic dysfunction among patients in the
      family practice clinic setting: a retrospective analysis.
AB  - CONTEXT: Relatively little has been published about contemporary use of
      osteopathic manipulative treatment (OMT) in family practice. OBJECTIVE: To
      provide an "epidemiology" of somatic dysfunction, assessing prevalence and
      severity of somatic dysfunction encountered in the family practice setting, also
      characterizing physician use of OMT. DESIGN: Retrospective analysis of Outpatient
      Osteopathic SOAP Note Form data collected in 1998 and 1999 by 20 osteopathic
      medical trainee-investigators under the supervision of seven site-based
      osteopathic physicians. SETTING: Three university-based, osteopathic family
      practice clinics. RESULTS: The authors analyzed records for 1331 patient
      encounters and 424 adult patients. The mean (SD) age of patients was 56.9 years
      (16.2 years), and 71% were women. The median number of days between repeat
      encounters was 29 days. Somatic dysfunction was diagnosed in 418 (31%) patient
      encounters, affecting a total of 1199 anatomic regions (2.9+/-1.2 anatomic
      regions per patient). Investigators used OMT in 335 (25%) patient encounters to
      treat a total of 952 anatomic regions (2.8+/-1.2 anatomic regions per patient).
      For women, the odds ratio for receiving OMT was 1.4 (95% confidence interval
      [CI], 1.0-2.2); for patients using analgesics, anti-inflammatory agents, or
      muscle relaxants, the odds ratio was 2.2 (95% CI, 1.2-4.1). Immediately after
      OMT, investigators reported that patients' somatic dysfunction resolved or
      improved in a total of 747 (96%) anatomic regions and remained unchanged in 32
      (4%) anatomic regions (P<.001). The authors used cluster analysis to classify
      anatomic regions by prevalence and severity of somatic dysfunction. CONCLUSION:
      Somatic dysfunction was diagnosed in almost one-third of patient encounters. In
      one-quarter of patient encounters, investigators used OMT.

PMID- 16424464
TI  - Surgical care in the 21st century.

PMID- 16424465
TI  - Survey of osteopathic and allopathic residents' attitudes toward osteopathic
      manipulative treatment.
AB  - More than 50% of new osteopathic physicians receive their residency training in
      programs accredited by the Accreditation Council for Graduate Medical Education
      (ACGME) rather than in programs approved by the American Osteopathic Association
      (AOA). To examine the implications of this training pattern for trends in the
      practice of osteopathic manipulative treatment (OMT), the authors surveyed
      attitudes toward OMT with questionnaires targeted to osteopathic and allopathic
      residents in family medicine residency programs. Osteopathic residents in
      specialties other than family medicine were also surveyed. Differences in views
      between osteopathic residents in AOA-approved and ACGME-accredited programs--as
      well as the views of the allopathic residents--were analyzed using chi(2) tests.
      Fewer osteopathic residents in ACGME-accredited family medicine programs (39.5%)
      reported frequent use of OMT than did osteopathic residents in AOA-approved
      family medicine programs (67.9%). This difference appears to result more from
      experiences during residency training than from expectations formed before
      residency training. Ninety percent of the allopathic residents who responded to
      the survey said they believed that OMT is effective for treating somatic
      dysfunction. Moreover, 70.9% of allopathic physicians indicated they had at least
      some interest in learning OMT. To the authors' knowledge, this study was the
      first to quantify a change in attitude of allopathic residents toward a more
      positive view of osteopathic medicine.

PMID- 16424466
TI  - Use of osteopathic manipulative treatment for iliotibial band friction syndrome.
AB  - Iliotibial band friction syndrome (ITBFS) has long been recognized as one of the
      most common lower-extremity injuries in athletes, especially in long-distance
      runners. Conservative therapy, including rest, ice, heat, stretching, and the use
      of anti-inflammatory medications, has been effective in helping athletes return
      to full competition, but athletes still miss much time in their sports because of
      ITBFS. The author presents a case of a 30-year-old distance runner with ITBFS
      whose symptoms were reduced with the help of osteopathic manipulative treatment,
      specifically the counterstrain technique. This technique allows for relief of
      pain at a tender point by moving the affected body part into its position of
      greatest comfort, aiding in the reduction of proprioceptor activity. In the
      present case, the tender point was located from 0 to 3 cm (most commonly 2 cm)
      proximal to the lateral femoral epicondyle. There is no prior documentation of
      the osteopathic manipulation of this specific tender point. Thus, this case
      report reflects an initial identification of the distal iliotibial band tender
      point and a new therapeutic modality for ITBFS.

PMID- 16424467
TI  - Personal knowledge.

PMID- 16424468
TI  - Using personal health information in medical research.

PMID- 16424469
TI  - Turning around NHS deficits.

PMID- 16424470
TI  - Naltrexone and problems in pain management.

PMID- 16424472
TI  - Surgery journal bans authors who hide conflicts of interest.

PMID- 16424471
TI  - Intrapleural streptokinase for pleural infection.

PMID- 16424474
TI  - Campaigners predict a complete public smoking ban for England.

PMID- 16424473
TI  - Hospital trust prosecuted for not supervising junior doctors.

PMID- 16424475
TI  - Turkey reports more cases as Asia prepares for bird flu.

PMID- 16424477
TI  - Ultra-Orthodox Jews criticised over circumcision practice.

PMID- 16424478
TI  - Roma women were unlawfully sterilised.

PMID- 16424481
TI  - Cloning pioneer denies intentionally falsifying results.

PMID- 16424489
TI  - Doctors decry Darfur "genocide".

PMID- 16424483
TI  - Prostate cancer patients get worse care than other cancer patients.

PMID- 16424492
TI  - Treatment of rheumatoid arthritis.

PMID- 16424493
TI  - Pulmonary embolism in hospital practice.

PMID- 16424494
TI  - Medical treatment of early breast cancer. III: chemotherapy.

PMID- 16424498
TI  - Evidence will help achieve consensus.

PMID- 16424496
TI  - Consent, confidentiality, and the Data Protection Act.

PMID- 16424499
TI  - Fighting cancer with oncolytic viruses.

PMID- 16424501
TI  - Cannabis confusions.

PMID- 16424500
TI  - Cannabis and psychosis.

PMID- 16424502
TI  - US flu mortality estimates are based on solid science.

PMID- 16424503
TI  - JAMA's policy on industry sponsored studies.

PMID- 16424504
TI  - Dummies and SIDS: low response rates generate considerable uncertainty.

PMID- 16424505
TI  - Dummies and SIDS: causality has not been established.

PMID- 16424506
TI  - Stockpiling of raw material for oseltamivir is not justified.

PMID- 16424507
TI  - Resistance to HIV drugs in UK may be lower in some areas.

PMID- 16424508
TI  - Mobile medical teams rethink.

PMID- 16424509
TI  - Funduscopy: to dilate or not? Other drugs can cause partial pupil dilatation.

PMID- 16424510
TI  - Funduscopy: to dilate or not? Precipitation of angle closure may not be a
      disservice.

PMID- 16424511
TI  - Don't discount magnet therapy.

PMID- 16424512
TI  - Wishful thinking about primary care in 2015.

PMID- 16424513
TI  - Patients get four choices for NHS treatments: choose and book will hinder
      development of good outpatient services.

PMID- 16424514
TI  - Patients get four choices for NHS treatments: choose and book has not left the
      station.

PMID- 16424515
TI  - Can erectile dysfunction drug use lead to ischaemic optic neuropathy?

PMID- 16424516
TI  - Which treatment is best for which AMD patient?

PMID- 16424518
TI  - How should we manage an amblyopic patient with cataract?

PMID- 16424517
TI  - The rising cost of glaucoma drugs.

PMID- 16424519
TI  - Cataract blindness and visual outcome of cataract surgery in a tribal area in
      Pakistan.
AB  - AIM: To estimate the rates of cataract blindness and cataract surgical coverage
      and to assess the visual outcome of cataract surgery among individuals aged > or
      =50 years in Orakzai Agency, Pakistan. METHODS: 1600 individuals aged > or =50
      years were selected using probability proportional to size sampling. The main
      outcome measure was bilateral cataract blindness which was defined as visual
      acuity of <3/60 in the better eye with best available correction and with obvious
      central lens opacities/absence of red reflex in both eyes. RESULTS: A total of
      1549 people were examined; the coverage rate was 96.8%. Of individuals who were
      examined, 958 (61.8%) were men. The overall prevalence of bilateral cataract
      blindness was 4.8% (95% CI: 3.8% to 5.9%). Women had a 2.1-fold greater
      prevalence of bilateral cataract blindness than men (7.1% (5.0% to 9.2%) v 3.4%
      (2.3% to 4.6%); p = <0.0001). However, cataract surgical coverage rates were
      lower for women than men. The overall quality of previous cataract surgery was
      poor: 43.1% eyes with cataract surgery had VA <6/60. 73.3% people with bilateral
      cataract blindness reported they could not undergo cataract surgery because they
      were too poor to afford its cost. CONCLUSION: The unacceptably high rates of
      cataract blindness and poor affordability and visual outcome of cataract surgery
      calls for the establishment, in the agency, of static cataract surgical services
      that are high quality, affordable, and gender sensitive.

PMID- 16424520
TI  - Microbial contamination of preservative free eye drops in multiple application
      containers.
AB  - BACKGROUND/AIMS: The majority of eye drops used in the United Kingdom contain
      preservatives and are bottled in plastic containers. Preservative free drops are
      used to avoid ocular irritation and allergies in certain individuals. The aim of
      this study was to investigate the incidence of microbial contamination of
      preservative free drops dispensed from multiusage containers. METHODS: Eye drop
      bottles were collected from patients attending the Tennent Institute of
      Ophthalmology outpatient and inpatient departments. The bottles were collected on
      day 3 (for inpatients) and day 7 (for outpatients) of use. The drops were
      inoculated onto different culture plates (chocolate agar, blood agar, fungal
      culture media, and enriched media) and the resulting microbial growth was
      identified using standard microbial identification techniques. RESULTS: 95 eye
      drop bottles were collected, containing a variety of 10 different eye drops.
      Significant bacterial growth was found in eight bottles. In total, seven
      different types of organism were identified from the eye drops. The organisms
      identified were Staphylococcus aureus, coagulase negative staphylococcus,
      Bacillus spp, Serattia spp, Klebsiella oxytoca, Enterobacter cloacae, and alpha
      streptococcus. Staph aureus was the commonest microbial organism. CONCLUSION:
      Preservative free eye drops in multiple application containers are at risk of
      contamination by potentially pathogenic micro-organisms.

PMID- 16424521
TI  - Anterior chamber depth measurement by optical pachymetry: systematic difference
      using the Haag-Streit attachments.
AB  - BACKGROUND/AIM: Haag-Streit recommends that for the most accurate anterior
      chamber depth (ACD) results, the corneal thickness, as determined with attachment
      No I, should be deducted from a measurement from corneal epithelium to the
      anterior lens surface, made with attachment No II (method A). Often
      ophthalmologists use the measurement made from the corneal endothelium to the
      anterior lens surface, using only attachment No II (method B), which is a simpler
      and faster method. This study examined agreement between methods A and B.
      METHODS: Two studies were conducted independently by each author. PHA measured
      127 (27 men, 100 women; mean age, 66.9 years) consecutive Danish patients
      referred for evaluation because of possible angle closure. RRB measured 109
      subjects (30 men, 79 women; mean age, 61.3 years) consecutively from a population
      based glaucoma survey in Rom Klao, Thailand. RESULTS: Using method A, mean ACD
      was 1.97 mm (SD 0.29) in the Danish study and 2.59 mm (SD 0.27) in the Thai
      study. ACD measured with method B was significantly (p<0.001) deeper than method
      A in both studies (Danes: difference = 0.118 (95% CI: 0.109 to 0.127); Thais:
      difference = 0.166 mm (95% CI: 0.158 to 0.174)). With an increase in ACD of 1 mm,
      the methodological difference increased by 0.052 mm (regression formula:
      difference (B - A) = 0.0667 x mean ACD - 0.0148; R(2) = 0.31). This positive
      correlation did not differ significantly between the two studies. CONCLUSIONS:
      The relevance and importance of estimating ACD as a risk factor in primary angle
      closure glaucoma suspects and patients has been repeatedly emphasised. This is
      the first empirical study to quantify the difference in ACD using these two
      methods in two samples, one clinic based (angle closure suspects) and the other
      population based. The size of the methodological difference has a level that
      corresponds to the age reduction of ACD per decade, or to about 6% of ACD in a
      given eye. These findings highlight the importance of clinicians recognising that
      these two methods will give different results and recommend that one should
      standardise ACD measurements using the Haag-Streit optical pachymeter.

PMID- 16424522
TI  - The safety and efficacy of combined phacoemulsification and trabeculectomy with
      releasable sutures.
AB  - AIM: To evaluate the combined phacoemulsification with acrylic intraocular lens
      implantation and trabeculectomy with releasable sutures, without the use of
      antimetabolites, performed by one surgeon. METHODS: A retrospective analysis was
      performed on 251 eyes of 198 patients after a combined phaco/trabeculectomy
      procedure, followed up for an average of 16 months for vision, intraocular
      pressure (IOP), and number of glaucoma medications. Cox proportional hazard
      regression analysis provided measures of relative risk (RR) or hazards ratios and
      95% confidence intervals (CIs) associated with the occurrence of several
      conditions or complications of surgery. RESULTS: Mean preoperative variables were
      best corrected vision, 0.6 (SD 0.4) logMAR (20/80 Snellen); IOP, 18.7 (4.9) mm
      Hg; and number of glaucoma medications, 1.7 (0.8). Mean postoperative results
      were best corrected vision, 0.2 (0.4) logMAR (20/32 Snellen); IOP, 15.1 (3.2) mm
      Hg; and number of glaucoma medications, 0.3 (0.6). Postoperatively, the mean
      decreases from baseline were 19.2% for IOP and 84.1% for number of glaucoma
      medications; 85% of eyes required fewer glaucoma medications and 78% of eyes were
      medication free, with IOP control. There were no significant operative or
      postoperative complications. CONCLUSION: Combined phacoemulsification and
      trabeculectomy with releasable sutures, in the absence of antimetabolites, is a
      safe, effective, and stable alternative for patients with cataracts and glaucoma.

PMID- 16424523
TI  - Colour vision defects in asymptomatic carriers of the Leber's hereditary optic
      neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a
      case-control study.
AB  - AIMS: To determine if asymptomatic carriers from a previously identified large
      pedigree of the Leber's hereditary optic neuropathy (LHON) 11778 mtDNA mutation
      have colour vision deficits. METHODS: As part of a comprehensive analysis of over
      200 members of a large Brazilian LHON pedigree spanning seven generations, colour
      vision tests were obtained from 91 members. Colour vision was tested one eye at a
      time using the Farnsworth-Munsell 100 (FM-100) hue colour vision test. The test
      was administered under uniform conditions, taking into account: ambient light
      levels, daylight colour temperature of 6700 kelvin, and neutral uniform
      background. Tests were scored using the FM-100 MS-Excel computer scoring program.
      Defects were determined and categorised as tritan, deutan, or protan.
      Categorisation of each dyschromatopsia was based on review of demonstrated axis
      computer generated plots and age adjusted error scores which coincided with
      Verriest 95% confidence intervals. Only the axis with the greatest magnitude
      error score was used to classify the defect. 55 of the 91 test subjects were LHON
      mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The
      remaining 36 subjects were age matched non-blood relatives (off pedigree), who
      served as controls. RESULTS: 27 of 55 carriers (49.10%) were shown to have colour
      vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the
      carrier group were tritan defects and the remaining 14 (52%) were deutan defects.
      Nine of the 27 (33%) abnormals in the carrier group were identified as having
      bilateral defects. Six of these were deutan, and the remaining three were tritan
      dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to
      have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The
      remaining one was a tritan defect. The difference between the two groups using a
      chi(2) test with one degree of freedom was statistically significant with a p
      value less that 0.001. CONCLUSIONS: Until now, LHON has always been characterised
      by a sudden, devastating vision loss. Asymptomatic carriers, those without vision
      loss, were considered unaffected by the disease. It now appears that asymptomatic
      carriers of the LHON mutation are affected by colour vision defects and may
      manifest other subtle, yet chronic, changes.

PMID- 16424524
TI  - Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile
      dysfunction.
AB  - AIM: To determine the association between Viagra (sildenafil) and Cialis
      (tadalafil) and non-arteritic anterior ischaemic optic neuropathy (NAION).
      METHODS: A retrospective matched case-control study was conducted. 38 cases of
      NAION in males were identified from an academic ophthalmology practice in
      Birmingham, Alabama, and matched (on age) to 38 controls without a history of
      NAION. Self reported information regarding past and current use of Viagra and/or
      Cialis was obtained via a telephone questionnaire from interviewers who were not
      blind to case status. RESULTS: Overall, males with NAION were no more likely to
      report a history of Viagra or Cialis use compared to similarly aged controls (odd
      ratio (OR) 1.75, 95% confidence interval (CI) 0.48 to 6.30 and OR 1.82, 95% CI
      0.21 to 15.39). However, for those with a history of myocardial infarction, a
      statistically significant association was observed (OR 10.7, 95% CI 1.3 to 95.8).
      A similar association was observed for those with a history of hypertension
      though it lacked statistical significance (OR 6.9, 95% CI 0.8 to 63.6).
      CONCLUSIONS: For men with a history of myocardial infarction or hypertension the
      use of Viagra or Cialis may increase the risk of NAION. Physicians prescribing
      these medications to patients with these conditions should warn them about the
      potential risk of NAION.

PMID- 16424525
TI  - Long term results after transpupillary thermotherapy in eyes with occult
      choroidal neovascularisation associated with age related macular degeneration: a
      prospective trial.
AB  - AIM: To evaluate long term results after transpupillary thermotherapy (TTT) in
      eyes with exudative age related macular degeneration. METHODS: In a prospective
      clinical study eyes with occult or predominantly occult choroidal
      neovascularisation and no pretreatment were scheduled to have a TTT with a power
      of 630 mW. Visual acuity for far and near distances as well as contrast
      sensitivity were evaluated 6, 12, and 24 months postoperatively and statistically
      analysed. RESULTS: 47 eyes fulfilled the inclusion criteria. Overall, 70% of the
      patients showed an improved (14%) or had unchanged (56%) ETDRS vision after 24
      months. Reading vision was stabilised (51%) or better (5%) in 56% of the eyes at
      this time. However, the increasing number of eyes with severe deterioration
      resulted in a significant decrease of both parameters over time (p = 0.0002 and p
      = 0.0003, respectively). Contrast sensitivity could be maintained (70%) or
      improved (9%) in 79%. Statistical analyses indicated a trend but no significant
      decrease over time (p = 0.056). CONCLUSION: Although in the majority of patients
      far and near distance acuity could be stabilised on average a significant
      decrease over time after TTT was observed. Statistical comparison of months 12
      and 24 showed no further deterioration.

PMID- 16424526
TI  - The rising cost of glaucoma drugs in Ireland 1996-2003.
AB  - BACKGROUND: Glaucoma affects approximately 2% of the population in developed
      countries and is estimated to affect 67 million people worldwide. The authors
      investigated the effect of the introduction of new medications on the volume and
      cost of drugs for glaucoma in two countries, Northern Ireland (NI, population
      approximately 1.7 million) and the Republic of Ireland (ROI, population
      approximately 3.9 million) in the 8 years from 1996 to 2003. They also looked at
      the surgical rates for glaucoma within the same time period for the two
      countries. METHODS: A retrospective analysis was performed of drug costs,
      prescribing data, and operation rates for glaucoma in Ireland from January 1996
      to December 2003. Information regarding costs and volume were obtained for each
      type of glaucoma drug and these were then grouped into the glaucoma treatment
      subsections as found in the British National Formulary. The drug information was
      obtained from the Central Services Agency in NI and IMS Health in the ROI and
      included both public and private prescriptions. The information on surgical rates
      for glaucoma was obtained from the Department of Health and Social Services in NI
      and the Hospital In-patient Enquiry (HIPE) data national files in the ROI.
      RESULTS: There was a 30% increase in prescription items for glaucoma in NI and a
      59% increase in the ROI from 1996 to 2003. The costs increased more rapidly than
      the number of items: 227% in the ROI and 78% in NI from January 1996 to December
      2003. In the ROI, there was an average 19% year on year increase in costs. In NI,
      new drugs accounted for 40% of the quantity of prescription items for glaucoma
      and 63% of the market cost in 2003. In the ROI new drugs accounted for 57% of the
      quantity and 77% of the market cost for glaucoma in 2003; prostaglandin analogue
      drugs alone accounted for 53% of the cost. The number of trabeculectomies
      performed decreased by more than 60% in both countries. CONCLUSION: Volume and
      cost of glaucoma drugs increased dramatically in both NI and the ROI from 1996 to
      2003, probably the result of a combination of changing demographics and a
      changing approach towards the management of patients with glaucoma and ocular
      hypertension. In 2003 in the ROI, prostaglandin analogues were the most commonly
      prescribed class of drug for patients with glaucoma and/or ocular hypertension
      causing a profound rise in drug expenditure.

PMID- 16424527
TI  - Conjunctival epithelium improvement after systemic pilocarpine in patients with
      Sjogren's syndrome.
AB  - AIM: To evaluate the effect of oral pilocarpine treatment on conjunctival
      epithelium of patients with Sjogren's syndrome (SS). METHODS: 15 primary SS
      patients were included in this prospective, single masked, comparative study.
      Patients underwent oral pilocarpine treatment for 2 months and were studied
      before (T0) and after 1 month (T1), 2 months (T2), and 15 days after treatment
      suspension (T3). Systemic and ocular symptoms, tear film break up time (BUT),
      corneal fluorescein vital staining, Schirmer I test, tear basal secretion test,
      and conjunctival imprinting were performed. Student's t test and Mann-Whitney U
      test were used for statistics. RESULTS: The conjunctival imprinting showed an
      increase of goblet cells number at T1 (1.6 (1.2) v 0.6 (0.7) at T0, p = 0.025)
      improving at T2 (5.1 (1.7); p<0.001 v T0 and T1). At T3 the number of goblet
      cells significantly decreased (1.9 (1.1); p<0.001 v T2). An improvement of dry
      mouth started at T1 and returned towards baseline values at T3. For ocular
      symptoms, burning and foreign body sensation were improved at T1 while ocular
      dryness improved at T2. BUT showed a statistically significant improvement at T2.
      CONCLUSIONS: Oral pilocarpine induced an increase in goblet cells number and an
      amelioration of conjunctival epithelium not dependent on tear secretion.

PMID- 16424528
TI  - The association between epilation and corneal opacity among eyes with
      trachomatous trichiasis.
AB  - AIM: To examine the association between epilation and corneal opacity (CO) among
      trichiasis patients presenting for surgery. METHODS: Cross sectional data from
      the STAR trial were utilised. Patients presenting for trichiasis surgery in
      Wolayta Zone, Ethiopia, were evaluated for current trichiasis status. Number of
      inturned lashes, evidence of epilation, level of entropion, trichiasis duration,
      and CO were collected. The primary outcome was prevalence of CO, stratified by
      entropion and epilation status. RESULTS: Approximately 10% of eyes with mild
      entropion had CO, regardless of epilation status. Among eyes with moderate
      entropion, epilated eyes were less likely to have CO than non-epilated eyes (21%
      v 34% p = 0.002). The same association was seen in eyes with severe entropion:
      43% of epilated eyes while 74% of non-epilated eyes had CO (p<0.0001). Presence
      of CO increased with age. Adjusted models showed a protective effect of epilation
      in eyes with moderate or severe entropion (OR: 0.51; 95% CI: 0.32 to 0.83 and OR:
      0.24; 95% CI: 0.13 to 0.45, respectively). Among eyes with mild entropion there
      was no difference in the prevalence of CO comparing eyes that were epilated with
      those that were not epilated. CONCLUSION: Entropion was the most significant
      predictor of CO. Cross sectional associations suggest that epilation may not be
      helpful for eyes with mild entropion, but may offer protection against CO in eyes
      with moderate to severe entropion. Epilation should not be a substitute for
      trichiasis surgery, however, as 43% of eyes with severe entropion that were
      epilated still had CO.

PMID- 16424529
TI  - Mitomycin C augmented glaucoma surgery: evolution of filtering bleb avascularity,
      transconjunctival oozing, and leaks.
AB  - AIMS: To prospectively study the evolution of possible high risk features of
      conjunctival filtration blebs like avascularity, transconjunctival oozing (TCO),
      and leaks after mitomycin C (MMC) enhanced glaucoma surgery. METHODS: Single
      observer, 2 year prospective study on bleb characteristics of 125 eyes of 125
      consecutive patients who had MMC augmented glaucoma surgery with initially
      successful filtration. MMC (0.2 mg/ml for 2 minutes in most cases) was applied on
      the area of the scleral flap before dissection. Glaucoma surgeries included were
      trabeculectomy, deep sclerectomy, and combined procedures. A dry fluorescein
      strip was applied on the avascular part of the bleb and observed for aqueous
      egress with flow (point leak, PL) or without (TCO). RESULTS: The mean time (95%
      CI) for observing bleb avascularity, TCO, and bleb leaks were 106 days (69 to
      143), 208 days (155 to 261), and 609 days (559 to 659), respectively. Bleb leaks
      were observed in 17 eyes (13.6%)-15 (24.6%) in the trabeculectomy group and two
      (3.1%) in the deep sclerectomy group (p = 0.003). Kaplan-Meier survival analyses
      showed that the probability of observing bleb avascularity at sixth, 12th, and
      24th month after surgery was 56%, 71%, and 73%, respectively. In eyes with
      avascular blebs, the probability of developing TCO and leaks was 77% and 1% at 6
      months, 81% and 12% at 12 months, and 95% and 26% at 24 months, respectively.
      Cox's regression analyses and log rank tests showed that eyes with larger
      avascular blebs (>4 mm) were more likely to develop TCO (hazard ratio 3.77, p =
      0.001) and delayed bleb leaks were more likely to be seen in eyes of the
      trabeculectomy group rather than the deep sclerectomy group (hazard ratio 0.06, p
      = 0.0006). CONCLUSIONS: MMC application over the area of scleral flap dissection
      during glaucoma surgery is associated with a high incidence of bleb avascularity,
      TCO, and delayed bleb leaks. Most eyes developed bleb avascularity within the
      first year after surgery. TCO will eventually be seen in all eyes with avascular
      blebs and the incidence of leaks gradually increases with time. This study shows
      that patients with eyes undergoing glaucoma surgery with MMC and avascular blebs
      should be monitored indefinitely.

PMID- 16424530
TI  - Three dimensional optic disc visualisation from stereo images via dual
      registration and ocular media optical correction.
AB  - BACKGROUND/AIMS: The three dimensional (3-D) visualisation of the optic disc in
      true colour will give essential meaning in clinical application. It is not only
      useful for clinicians in the evaluation of the condition of the optic disc, but
      it also simplifies the pathological diagnosis and disease progression monitoring.
      This paper describes a complete 3-D optic disc reconstruction method from a pair
      of stereo images by a series of robust procedures including camera calibration,
      image registration, depth recovery, and ocular media optical inclusion. METHODS:
      Two registration techniques (correlation and feature based methods) are combined
      together to prune the uncertain matching points in order to improve the overall
      accuracy of registration. The ocular media within the eyeball are lump modelled
      as a single lens and integrated into the reconstruction process to obtain an
      accurate 3-D optic disc image. CONCLUSION: The recovered 3-D optic disc images
      show good consistency and compatibility when compared with the results from
      Heidelberg retina tomography (HRT) under clinical validation, with an additional
      advantage of implementing a more economical and conventional mode of retinal
      image acquisition.

PMID- 16424531
TI  - A new quality assessment parameter for optical coherence tomography.
AB  - AIM: To create a new, automated method of evaluating the quality of optical
      coherence tomography (OCT) images and to compare its image quality discriminating
      ability with the quality assessment parameters signal to noise ratio (SNR) and
      signal strength (SS). METHODS: A new OCT image quality assessment parameter,
      quality index (QI), was created. OCT images (linear macular scan, peripapillary
      circular scan, and optic nerve head scan) were analysed using the latest
      StratusOCT system. SNR and SS were collected for each image. QI was calculated
      based on image histogram information using a software program of our own design.
      To evaluate the performance of these parameters, the results were compared with
      subjective three level grading (excellent, acceptable, and poor) performed by
      three OCT experts. RESULTS: 63 images of 21 subjects (seven each for normal,
      early/moderate, and advanced glaucoma) were enrolled in this study. Subjects were
      selected in a consecutive and retrospective fashion from our OCT imaging
      database. There were significant differences in SNR, SS, and QI between excellent
      and poor images (p = 0.04, p = 0.002, and p<0.001, respectively, Wilcoxon test)
      and between acceptable and poor images (p = 0.02, p<0.001, and p<0.001,
      respectively). Only QI showed significant difference between excellent and
      acceptable images (p = 0.001). Areas under the receiver operating characteristics
      (ROC) curve for discrimination of poor from excellent/acceptable images were 0.68
      (SNR), 0.89 (IQP), and 0.99 (QI). CONCLUSION: A quality index such as QI may
      permit automated objective and quantitative assessment of OCT image quality that
      performs similarly to an expert human observer.

PMID- 16424533
TI  - Impaired retinal autoregulation in small retinal arterioles before and after
      focal laser treatment for diabetic maculopathy.
AB  - AIMS: To study the effect of an acute increase in the arterial blood pressure on
      the diameter response of retinal arterioles supplying areas with focal diabetic
      macular oedema before and after laser photocoagulation, and control arterioles
      supplying areas without oedema. METHODS: In 17 diabetic patients the diameter
      response of arterioles after an increase in the arterial blood pressure induced
      by isometric exercise was studied using the retinal vessel analyser (RVA). In
      each patient a study arteriole supplying a focal area of macular oedema as well
      as a control arteriole supplying a retinal area without retinopathy lesions was
      selected, and the diameter response of these vessels was performed immediately
      before, and 1 hour and 3 months after focal laser photocoagulation of the focal
      oedema area. RESULTS: The diameter response was impaired in both study arterioles
      and control arterioles before focal laser photocoagulation. The treatment induced
      regression of the focal retinal oedema, but did not affect the diameter response
      in the arteriole supplying this area (p = 0.85). CONCLUSION: Impairment of the
      diameter response in small arterioles from diabetic patients does not parallel
      the regional distribution of retinopathy lesions. Other factors than disturbed
      autoregulation are probably involved in generating flow disturbances and oedema
      in diabetic maculopathy.

PMID- 16424532
TI  - Ultrahigh resolution optical coherence tomography in non-exudative age related
      macular degeneration.
AB  - AIM: To describe the appearance of the non-exudative forms of age related macular
      degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography
      (UHR-OCT). METHODS: A UHR-OCT ophthalmic imaging system, which utilises a
      femtosecond laser light source capable of approximately 3 mum axial resolution,
      was employed to obtain retinal cross sectional images of patients with non
      exudative AMD. Observational studies of the resulting retinal images were
      performed. RESULTS: 52 eyes of 42 patients with the clinical diagnosis of non
      exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had
      the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes.
      In these patients, three patterns of drusen were apparent on UHR-OCT: (1)
      distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular
      drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative
      AMD had evidence of fluid under the retina or RPE. Two of these three patients
      had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT.
      CONCLUSION: With the increased resolution of UHR-OCT compared to standard OCT,
      the involvement of the outer retinal layers are more clearly defined. UHR-OCT may
      allow for the detection of early exudative changes not visible clinically or by
      angiography.

PMID- 16424534
TI  - Uncorrected refractive error in Singapore teenagers.
AB  - AIM: To study the prevalence rate of uncorrected refractive error and associated
      risk factors among Singapore schoolchildren aged 12-16 years (grade 7). METHODS:
      A cross sectional study of 628 participants (participation rate 99.8%) was
      conducted in two schools. An interviewer led questionnaire asking about
      sociodemographic variables and risk factors was administered. Refractive errors
      were measured using a table mounted autorefractor. Participants with habitual
      visual acuity (VA) of 0.2 logMAR or worse underwent subjective refraction.
      Uncorrected refractive error was defined as improvement of at least 0.2 logMAR in
      best corrected visual acuity after subjective refraction. RESULTS: The prevalence
      rate of uncorrected refractive error was 22.3% (95% confidence interval (CI)
      19.0% to 25.5%). The multivariate adjusted odds ratio of uncorrected refractive
      error in students with the lowest academic ability was 2.24 (95% CI 1.34 to
      3.73). Increasing time interval since the last visit to an eye care provider
      increased the risk of uncorrected refractive error (trend p = 0.001). CONCLUSION:
      Uncorrected refractive error was a significant problem among Singapore students
      aged 12-16 years (grade 7). Uncorrected refractive error was more common among
      students with low academic ability or those who had not visited an eye care
      provider for a long time.

PMID- 16424535
TI  - Adal-1 bioadhesive for sutureless recession muscle surgery: a clinical trial.
AB  - AIMS: To evaluate the efficacy and biotolerance of the Adal-1 adhesive for muscle
      sealing in strabismus surgery. METHODS: 27 eyes were included in the study: 17 in
      the control group and 10 in the study group. Surgery was performed on the
      recession of the horizontal rectus muscles. In the control group the muscle was
      joined to the sclera by a Vicryl 7/0 suture. In the study group, the Adal-1
      adhesive was used instead. The efficacy of the sealing of the muscle to the
      sclera and the biotolerance of the surrounding tissues were evaluated. RESULTS:
      The muscular recession in the control group was 8.17 (SD 2.38) with displacement
      of the sealing point of 0.02 (1.7) mm. In the group sealed with adhesive, the
      muscular recession was 9.09 (3.08) and the displacement was 0.15 (1.56) mm, with
      no significant differences between the techniques (p<0.05). The inflammation of
      the surrounding tissues in the immediate postoperative period was greater with
      the suture technique (p>0.05), but there were no differences in the other
      postoperative periods (Mann-Whitney U test). CONCLUSION: Adal-1 was an effective
      and safe alternative to sutures in muscle recession for strabismus surgery in
      this study.

PMID- 16424536
TI  - Immunophenotypic markers to differentiate between benign and malignant
      melanocytic lesions.
AB  - BACKGROUND/AIMS: The authors investigated the expression of S100A1, S100A6,
      S100B, MelanA, and CEA in conjunctival naevi, primary acquired melanosis (PAM),
      conjunctival melanoma, and uveal melanoma in order to assess their potential
      usefulness in the pathological differential diagnosis of these entities. METHODS:
      Paraffin embedded sections of 18 conjunctival naevi, 14 PAM, 16 conjunctival
      melanomas, and 20 uveal melanomas were immunostained for S100A1, S100A6, S100B,
      MelanA, and CEA, and expression was scored semiquantitatively. RESULTS:
      Expression of S100A1 differed significantly between conjunctival naevi and
      conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%,
      respectively. Conjunctival melanomas had high average scores for S100A1 and S100B
      (71.4%, 62.9%, respectively), while uveal melanomas also had high S100A1 but low
      S100B scores (88.5%, 18.5%, respectively). MelanA was highly variable; naevi and
      uveal melanoma had higher average scores than conjunctival melanoma. CEA was
      hardly detectable in all four groups. CONCLUSION: S100A1 seems to be a possible
      candidate to differentiate conjunctival naevi from conjunctival melanoma. S100B
      seems to differentiate between uveal melanoma and conjunctival melanoma. However,
      the study size was small and therefore the data have to be confirmed by others.

PMID- 16424538
TI  - Muller cell expression of glutamate cycle related proteins and anti-apoptotic
      proteins in early human retinal development.
AB  - AIMS: The distribution of glutamate cycle related proteins (glutamine synthetase
      (GS) and GLAST) and anti-apoptotic proteins (Bcl-2 and Bcl-X) was investigated in
      Muller cells during early human retinal development, relative to the onset of
      expression of synaptophysin, a presynaptic vesicle protein. METHODS: Using frozen
      sections of human fetal eyes (13-22 weeks gestation) (n = 10), Bcl-2, Bcl-X, GS,
      GLAST, and synaptophysin immunoreactivities (IR) were imaged using fluorescence
      microscopy and plotted as a function of eccentricity from the incipient fovea.
      Frozen sections of adult human retina (n = 4) were immunolabelled with antibodies
      to Bcl-2 and Bcl-X. RESULTS: Muller cell immunoreactivity for GS, GLAST, and Bcl
      2 was initially detected in the incipient fovea, and then at more peripheral
      locations with increasing age. Synaptophysin-IR appeared earlier than all other
      target proteins. Within the synaptophysin-IR region, mature (differentiated)
      Muller cells expressed both Bcl-2 and Bcl-X-IR from 13 weeks gestation, ahead of
      GS-IR and GLAST-IR that were first seen at 14 weeks gestation. Additionally, from
      as early as 13 weeks gestation, ganglion cells and immature neuronal progenitor
      cells across the entire retina expressed Bcl-2-IR and Bcl-X-IR, respectively. In
      adult retina, ganglion cells and some bipolar cells expressed Bcl-X but not Bcl
      2. CONCLUSION: Muller cells express Bcl-2 and Bcl-X after synaptogenesis has
      commenced, but before the onset of GS and GLAST expression, suggesting a
      protective role for these proteins in Muller cells during the onset of
      glutamatergic transmission in early human retinal development.

PMID- 16424539
TI  - A2e mediated phototoxic effects of endoilluminators.
AB  - AIMS: To compare the theoretical retinal threshold time for endoilluminators and
      experimental phototoxic effect using A2e laden retinal pigment epithelial (RPE)
      cells. METHODS: The spectral irradiances of three types of 20 gauge and 25 gauge
      endoilluminators, currently commercially available from two manufacturers, were
      evaluated in conditions where the total beam spectral power was divided by the
      beam spot size at an estimated use distance of 5 mm from the retina. The retinal
      threshold time was calculated using the guidelines recommended by the
      International Commission on Non-Ionizing Radiation Protection. In vitro, A2e
      laden cells were evenly exposed to light for 30 minutes with a standard
      endoilluminator positioned 1 cm above the cells and the cell viability was
      assessed by WST-1 assay. RESULTS: The retinal threshold times were within 1
      minute for all the endoilluminators tested. A significant decrease in the
      viability of A2e laden RPE cells was observed after they were exposed to light
      from two of the three 20 gauge endoilluminators. Cell viability was not affected
      by the exposure to 25 gauge endoilluminators under the same conditions. There was
      no correlation between the theoretical threshold times and experimental data.
      CONCLUSIONS: Light exposure during vitrectomy can induce photochemical damage to
      the retina. Although the A2e laden RPE model may not correctly mimic a clinical
      situation, this model may be useful to estimate the possible photochemical damage
      to RPE cells that could not be deduced by a theoretical retinal hazard model.

PMID- 16424537
TI  - Analysis of corneal inflammation induced by cauterisation in CCR2 and MCP-1
      knockout mice.
AB  - AIM: To elucidate the role of CCR2/MCP-1 in corneal inflammation. METHODS: A
      cauterisation induced corneal inflammation model was used. The corneas were
      cauterised with silver nitrate in CCR2 knockout (KO) mice, MCP-1 KO mice, and
      control mice. Clinical signs such as corneal oedema and opacity were examined 96
      hours after cauterisation and the phenotypes of the cells infiltrating the cornea
      were analysed by flow cytometry. Corneal inflammation in neutrophil depleted mice
      was also analysed. RESULTS: After cauterisation both CCR2 KO and MCP-1 KO mice
      showed the same levels of corneal oedema and opacity as control mice. Flow
      cytometry revealed that in control mice most of the infiltrating cells were
      neutrophils and macrophages, whereas in both CCR2 KO mice and MCP-1 KO mice, the
      number of macrophages infiltrating the cornea were markedly reduced. However,
      prominent infiltrates of neutrophils were still observed in the cornea in CCR2 KO
      mice and MCP-1 KO mice. The depletion of neutrophils significantly reduced the
      oedema and opacity induced in the cornea by cauterisation. CONCLUSION: The CCR2
      and MCP-1 molecules are not essential for cauterisation induced corneal
      inflammation. Neutrophils, rather than migrated macrophages, are the final
      effector cells involved in inducing inflammation in this model.

PMID- 16424540
TI  - Cell viability effects of triamcinolone acetonide and preservative vehicle
      formulations.
AB  - AIM: To assess the effect of triamcinolone acetonide and preservative vehicle
      formulations on human retinal pigment epithelium (ARPE19) cells over a range of
      concentrations. METHODS: Triamcinolone acetonide, in its trade and preservative
      free formulations, along with the preservative vehicle were added to ARPE19 cell
      cultures in various concentrations (0.01-1.0 mg/ml). Cell viability was assessed
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at
      day 5 after exposure. Functionality of the cultured ARPE19 cell line was
      confirmed by exposure to a previously characterised toxic agent, tamoxifen.
      RESULTS: The ARPE19 cell line behaved as predicted with exposure to tamoxifen.
      All formulations caused significant reductions in ARPE19 cell viability at the
      highest concentrations (1.0 mg/ml for triamcinolone preparations and undiluted
      vehicle). Cell viability was reduced to the greatest degree in trade formulation
      triamcinolone, less so by the vehicle, and least by preservative free
      triamcinolone. At lower concentrations no significant effect on cell viability
      was observed, although cell viability was found to be inversely proportional to
      increasing concentration of all tested reagents CONCLUSIONS: Both the trade and
      preservative free formulations of triamcinolone acetonide as well as the vehicle
      result in cell loss at in vitro concentrations of 1 mg/ml. Although this
      represents theoretical vitreous concentrations achieved with current widespread
      therapeutic use it probably does not indicate the actual exposure of cells in
      their biological milieu. That cell viability was reduced most in the trade
      formulation suggests a possible potentiated inhibitory toxic effect of
      triamcinolone acetonide and vehicle at higher concentrations.

PMID- 16424541
TI  - A hypothesis to suggest that light is a risk factor in glaucoma and the
      mitochondrial optic neuropathies.
AB  - The authors propose that light entering the eye interacts with retinal ganglion
      cell (RGC) axon mitochondria to generate reactive oxygen intermediates (ROI) and
      that when these neurons are in an energetically low state, their capacity to
      remove these damaging molecules is exceeded and their survival is compromised.
      They suggest that in the initial stages of glaucoma, RGCs exist at a low energy
      level because of a reduced blood flow at the optic nerve head and that in the
      mitochondrial optic neuropathies (MONs), this results from a primary, genetic
      defect in aerobic metabolism. In these states RGCs function at a reduced energy
      level and incident light on the retina becomes a risk factor. Preliminary
      laboratory studies support this proposition. Firstly, the authors have shown that
      light is detrimental to isolated mitochondria in an intensity dependent manner.
      Secondly, light triggers apoptosis of cultured, transformed RGCs and this effect
      is exacerbated when the cells are nutritionally deprived. Detailed studies are
      under way to strengthen the proposed theory. On the basis of this proposal, the
      authors suggest that patients with optic neuropathies such as glaucoma or at risk
      of developing a MON may benefit from the use of spectral filters and reducing the
      intensity of light entering the eye.

PMID- 16424543
TI  - Rapid development of severe toxic retinopathy associated with continuous
      intravenous deferoxamine infusion.

PMID- 16424544
TI  - Epstein-Barr virus infected cells in the aqueous humour originated from nasal
      NK/T cell lymphoma.

PMID- 16424542
TI  - Ophthalmic pathology of genotypically confirmed von Hippel Lindau disease type 1.

PMID- 16424545
TI  - Phakomatous choristoma of the eyelid: a case with associated eye abnormalities.

PMID- 16424546
TI  - Granular cell tumour: a rare caruncle lesion.

PMID- 16424547
TI  - Topical brinzolamide and metabolic acidosis.

PMID- 16424548
TI  - Solar retinopathy in a patient with bipolar affective disorder.

PMID- 16424549
TI  - Anterior ischaemic optic neuropathy after rotator cuff surgery.

PMID- 16424550
TI  - Bilateral intraocular involvement in Lemierre's syndrome.

PMID- 16424551
TI  - Short and long term effect of combined cataract and glaucoma surgery with MMC on
      ocular dimensions.

PMID- 16424552
TI  - Intraocular pressure changes in the contralateral eye after trabeculectomy with
      mitomycin C.

PMID- 16424553
TI  - Identifying troxler.

PMID- 16424554
TI  - Status of ethical review and challenges in India.

PMID- 16424555
TI  - Clinically directed selective screening for HIV infection in hospitalized
      children.
AB  - BACKGROUND: As HIV infection presents with several manifestations, none of which
      is specific, several children are subjected to HIV testing. Very few studies have
      examined the issue of probability of HIV infection with a given clinical
      manifestation. AIM: To determine the probability of HIV infection when a child is
      hospitalized with at least one of the selected manifestations. MATERIAL AND
      METHODS: Children aged 18 mo and above, admitted to a tertiary care center in
      Mumbai, India with chronic diarrhea, severe malnutrition, persistent cough,
      generalized lymphadenopathy, oral thrush, hepatomegaly, repeated common
      infections, generalized dermatitis, chronic parotid swelling, recurrent bacterial
      infection, disseminated tuberculosis and/ or Pneumocystis carinii pneumonia were
      enrolled in a prospective study after obtaining informed consent. They were
      subjected to HIV testing using WHO-UNAIDS strategy II. The data obtained was
      analyzed using the Statistical Package For Social Sciences (SPSS) software
      program. RESULTS: Twenty-three (20 PERCENT) of the 115 children enrolled tested
      positive for HIV. The seropositivity rate for various features ranged from 9.1
      PERCENT for chronic diarrhea to 83.3 PERCENT for chronic dermatitis. Oral thrush,
      generalized dermatitis and generalized lymphadenopathy were the significant
      independent clinical risk factors for predicting HIV seropositivity. The
      probability of HIV infection was higher in children who had higher number of risk
      factors present concomitantly CONCLUSIONS: The probability of HIV infection in a
      child is dependent upon the nature and number of manifestations present.

PMID- 16424556
TI  - Sanitation: a call on resources for promoting urban child health.
AB  - Poor sanitation is known to increase the risk of morbidity and mortality from
      diarrhea among children. Several studies have found a high correlation between
      childhood morbidity and availability of sanitation services. It has been
      estimated that 1.7 million deaths each year, or 3.1 percent of all deaths are
      attributable to inadequate access to water, sanitation and hygiene. The urgency
      for sanitation in the urban environment stems from the fact that the urban poor
      live in crowded slums and informal settlements where sanitation facilities are
      particularly important for children's health and personal dignity. Demand for
      sanitation services has remained low, as livelihood priorities have been more
      pressing. There is a pressing need to get Governments and society to recognize
      the appalling toll created by poor sanitary conditions in urban poor settlements.
      Serious efforts should be made to develop local, national and international
      campaigns which promote convergence among programs aimed at urban health
      infrastructure, community development and education; motivate people to demand
      and maintain better sanitation; and place sanitation to the forefront of
      development and political dialogue.

PMID- 16424557
TI  - Voriconazole.
AB  - Voriconazole (VRZ) is a second-generation triazole antifungal agent active
      against many species of Aspergillus and Candida and acts by inhibiting ergosterol
      synthesis. VRZ has less nephrotoxicity and less infusion-related toxicity than
      that of Amphotericin B. Oral and parental formulation have similar
      pharmacokinetics and thus oral formulation shortens the duration of hospital
      stay. It is overall well tolerated but has significant drug interactions.

PMID- 16424558
TI  - The HIV-1 exposed neonate: outcome of intensive care management in the first week
      of life.
AB  - A prospective study was carried out to determine if the outcome in HIV-exposed
      neonates requiring intensive care (n=30) is different from that in HIV-unexposed
      neonates (n=40) requiring intensive care in the first week of postnatal life. It
      was noted that the outcome in terms of incidence of death and intensive care stay
      do not differ significantly in these two groups although some hematological
      parameters may be significantly different. Considering the fact that the outcome
      is not worse in HIV-exposed babies and that most of these babies ultimately turn
      out to be HIV-uninfected, these babies should not be deprived of intensive care,
      whenever necessary.

PMID- 16424559
TI  - Accuracy of parental and child's report of changes in symptoms of childhood
      asthma.
AB  - This cohort study was conducted to evaluate the accuracy of parental and child's
      reports of changes in asthma symptoms. Fifty three asthmatic children and their
      parents were interviewed at enrollment and after 4 and 8 weeks. The outcomes were
      parental and child's reports of changes in asthma symptoms, changes in mean daily
      symptom scores and changes in pulmonary function. Among patients 6 to 10 years
      old, parental reports correlated more strongly than child's reports with changes
      in mean daily symptom scores (r: 0.54 vs 0.23). In patients aged 11 years or
      older, parental and child's reports correlated comparably with changes in mean
      daily symptom scores (r 0.63 vs 0.57). In both age groups, neither parental nor
      child's reports correlated significantly with changes in pulmonary function. The
      relatively low coefficient of correlation between parental,child report with
      symptom score suggests that these may not be very accurate reflections of change
      in asthma status. Nevertheless, for the age group 6 to 10 year, parental reports
      are more reliable than child reports, while both are comparable in the age group
      11-18 years.

PMID- 16424560
TI  - Effects of cessation of a policy of neonatal fluconazole prophylaxis on fungal
      resurgence.
AB  - Fluconazole has been used as prophylaxis against systemic fungal infections in
      preterm neonates. We conducted a study to determine whether cessation of a policy
      of prophylactic fluconazole results in a resurgence of fungal infections in a
      unit. Neonates born in the 3 epoches: A 36-month pre-Fluconazole prophylaxis
      epoch (Group 1), a 21-month Fluconazole prophylaxis epoch (Group 2) and a 39
      month post Fluconazole prophylaxis epoch (Group 3) were compared for incidence
      and onset of fungal sepsis and resistance patterns. There was a decline in the
      incidence of fungal sepsis from Group 1 to Group 2, and it remained stable from
      Group 2 to Group 3. There was no significant difference in resistance to
      Fluconazole and to any of the azoles in Groups 1, 2 and 3 respectively.

PMID- 16424561
TI  - Thyroid dyshormonogenesis.
AB  - Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most
      common abnormality is absent or insufficient thyroid peroxidase enzyme.
      Perchlorate discharge test can be used to diagnose thyroid peroxidase deficiency.
      We report three siblings with hypothyroidism due to thyroid dyshormonogenesis.
      Early institution of therapy in these patients can prevent mental retardation and
      other features of hypothyroidism.

PMID- 16424562
TI  - Detection of 22 q11.2 hemizygous deletion by interphase FISH in a patient with
      features of CATCH 22 syndrome.
AB  - We report an eight years female child with clinical and molecular cytogenetic
      findings consistent with CATCH 22 syndrome characterized by cardiac defect,
      typical facial dysmorphism, mental deficiency and chromosome 22 q11.2 deletion.
      Interphase FISH with 22q 11.2 probe demonstrated hemizygous deletion in 98.5%
      nuclei. Interphase FISH for diagnosis of CATCH 22 syndrome has not been reported
      previously from India to our knowledge.

PMID- 16424563
TI  - Hereditary coagulation factor X deficiency.
AB  - Stuart Prower factor (Factor X) deficiency is a rare hereditary autosomal
      recessive coagulation disorder. We have come across three cases in the course of
      last 20 years at our institute. These patients presented with prolonged bleeding
      after minor trauma, epistaxis, subcutaneous bluish black nodules and two of them
      presented with history of consanguinity in parents. Hematological findings in
      correlation with clinical manifestations revealed severe factor X deficiency.

PMID- 16424564
TI  - Berardinelli seip syndrome.

PMID- 16424565
TI  - Bilateral triphalangeal thumbs.

PMID- 16424566
TI  - Ankyloglossia superior.

PMID- 16424567
TI  - An unusual cause of school refusal in a child.

PMID- 16424569
TI  - Schmid type metaphyseal chondrodysplasia.

PMID- 16424568
TI  - Child abuse where do we stand today?

PMID- 16424570
TI  - EBV associated hemophagocytic lymphohistiocytosis with spontaneous regression.

PMID- 16424571
TI  - Unusual congenital cystic adenomatoid malformation of the lung: a diagnostic
      dilemma.

PMID- 16424572
TI  - Clinical validation of the LKB model and parameter sets for predicting radiation
      induced pneumonitis from breast cancer radiotherapy.
AB  - The choice of the appropriate model and parameter set in determining the relation
      between the incidence of radiation pneumonitis and dose distribution in the lung
      is of great importance, especially in the case of breast radiotherapy where the
      observed incidence is fairly low. From our previous study based on 150 breast
      cancer patients, where the fits of dose-volume models to clinical data were
      estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters
      predicting radiation induced pneumonitis using clinical data from breast cancer
      radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the
      relative seriality is significantly better than the LKB NTCP model. However, the
      estimation of the different NTCP models was based on their goodness-of-fit on
      clinical data, using various sets of published parameters from other groups, and
      this fact may provisionally justify the results. Hence, we sought to investigate
      further the LKB model, by applying different published parameter sets for the
      very same group of patients, in order to be able to compare the results. It was
      shown that, depending on the parameter set applied, the LKB model is able to
      predict the incidence of radiation pneumonitis with acceptable accuracy,
      especially when implemented on a sub-group of patients (120) receiving [see
      text]|EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain
      radiobiological model on a given clinical case is closely related to the
      selection of the proper scoring criteria and parameter set as well as to the
      compatibility of the clinical case from which the data were derived.

PMID- 16424573
TI  - Dosimetric effects on the penumbra region of irregular multi-leaf collimated
      fields.
AB  - The dosimetric effect in the penumbra region for multi-leaf collimator (MLC)
      fields was studied using a Varian 21 EX linear accelerator. The beam profiles in
      the cross-line and in-line directions for MLC field configurations of varying
      lengths of protruded leaves, which are adjacent (on one or both sides) to the
      beam profile axes, were measured using a 6 MV photon beam. It was found that
      there is a decrease of dose in the 'edge' region of the protruded leaves' side in
      the cross-line profile, when the protruded leaves (upper and/or lower side) were
      moved out from 0.5 cm to 3 cm towards the central beam axis. When both the upper
      and lower portions of leaves were moved out forming a gap for the profile, the
      dose at the 'edge' region in the cross-line direction was decreased by about 20%
      and 6%, with the protruded length of leaves being 0.5 cm and 1 cm, respectively.
      The penumbra width of the cross-line profile increased with the protruded length
      of leaves when the gap width was 0.5 cm, and it was independent of the length
      when the width was increased larger than 1 cm. The Pinnacle treatment planning
      system could calculate the decrease of dose observed experimentally in the cross
      line profile, but an underestimation of about 30% was found when using version
      6.2b, which did not consider the leaf rounded end and tongue-and-groove effect.
      While the newly commissioned 7.4f, which considered the two aforementioned
      effects, made an improvement, it still underestimated the dose by 25% compared to
      the measurement. For the in-line profiles, both versions estimated the penumbra
      width well.

PMID- 16424574
TI  - Sequential, co-registered fluorine and proton field-cycled Overhauser imaging at
      a detection field of 59 mT.
AB  - In this work we show the feasibility of sequential, co-registered fluorine and
      proton field-cycled Overhauser imaging at a detection field of 59 mT. To this
      purpose we have built an RF coil assembly comprising an Alderman-Grant resonator
      for EPR irradiation at 127.7 MHz (evolution field of 4.5 mT) and a solenoidal
      coil for (19)F or (1)H MRI acquisition at the detection field of 59 mT. A
      removable tuning/matching circuit that allows the solenoid to be tuned to the
      (19)F frequency (2.346 MHz, FEDRI) or the (1)H frequency (2.494 MHz, PEDRI)
      without removing the sample was built and tested. Switching of the solenoid
      between the (19)F and (1)H frequency is thus achieved in less than 1 min. The co
      registered FC-FEDRI and FC-PEDRI images show higher enhancement in the sample
      regions with higher free radical concentration. This work is the first
      methodological step towards the development of an MRI scanner capable of
      acquiring morphological ((1)H) and physiological ((19)F) images in animal models
      at very low fields.

PMID- 16424575
TI  - Normalization in quantitative [18F]FDG PET imaging: the 'body surface area' may
      be a volume.
AB  - Non-invasive methods for quantifying [(18)F]FDG uptake in tumours often require
      normalization to either body weight or body surface area (BSA), as a surrogate
      for [(18)F]FDG distribution volume (DV). Whereas three dimensions are involved in
      DV and weight (assuming that weight is proportional to volume), only two
      dimensions are obviously involved in BSA. However, a fractal geometry
      interpretation, related to an allometric scaling, suggests that the so-called
      'body surface area' may stand for DV.

PMID- 16424576
TI  - The characterization of the Advanced Markus ionization chamber for use in
      reference electron dosimetry in the UK.
AB  - The IPEM Code of Practice (IPEM 2003) for electron dosimetry for radiotherapy
      beams recommends design requirements for parallel-plate ionization chambers used
      to determine absorbed dose to water in an electron beam. The Classic Markus
      design has been found not to meet these requirements. The Advanced Markus
      ionization chamber has been designed to rectify the problems associated with the
      Classic Markus ionization chamber. The response of three Advanced Markus
      ionization chambers was investigated and compared to the designated chamber
      types. Absorbed dose to water calibration factors were derived at the National
      Physical Laboratory (NPL) for each ionization chamber at seven electron energies
      in the range nominally 4-19 MeV. Investigations were carried out into chamber
      settling, polarity effects, ion recombination and the chamber perturbation. The
      response of the ionization chambers in a clinical beam was also investigated. In
      general all three Advanced Markus ionization chambers showed the same energy
      response. The magnitude of the polarity effect was typically 5% at a nominal
      energy of 4 MeV. There was discrepancy between the polarity measurements made at
      the NPL and in the clinic. The recommendation of this study is that this chamber
      type is not suitable for reference dosimetry in electron beams.

PMID- 16424578
TI  - Diffuse photon propagation in multilayered geometries.
AB  - Diffuse optical tomography (DOT) is an emerging functional medical imaging
      modality which aims to recover the optical properties of biological tissue. The
      forward problem of the light propagation of DOT can be modelled in the frequency
      domain as a diffusion equation with Robin boundary conditions. In the case of
      multilayered geometries with piecewise constant parameters, the forward problem
      is equivalent to a set of coupled Helmholtz equations. In this paper, we present
      solutions for the multilayered diffuse light propagation for a three-layer
      concentric sphere model using a series expansion method and for a general layered
      geometry using the boundary element method (BEM). Results are presented comparing
      these solutions to an independent Monte Carlo model, and for an example three
      layered head model.

PMID- 16424577
TI  - A method for the inter-calibration of a matrix of sensors.
AB  - We present a quick and easy method for the calibration of a matrix of sensors.
      The algorithm is based on a three-step irradiation procedure which relies only on
      the constancy of the delivered fluence at each step. With this method the gain of
      each sensor is derived relative to a reference detector. The algorithm has been
      applied to a matrix of (32 x 32) ionization chambers. After the calibration
      coefficients have been applied, by comparing the response of the matrix of
      chambers to a reference detector over a large field, we determined that the
      fluence measurement of individual chambers is better than 0.7%. The algorithm
      solves the cumbersome problem of the relative gain calibration of a matrix of a
      large number of sensors.

PMID- 16424579
TI  - Left ventricular motion reconstruction with a prolate spheroidal B-spline model.
AB  - Tagged cardiac magnetic resonance (MR) imaging can non-invasively image
      deformation of the left ventricular (LV) wall. Three-dimensional (3D) analysis of
      tag data requires fitting a deformation model to tag lines in the image data. In
      this paper, we present a 3D myocardial displacement and strain reconstruction
      method based on a B-spline deformation model defined in prolate spheroidal
      coordinates, which more closely matches the shape of the LV wall than existing
      Cartesian or cylindrical coordinate models. The prolate spheroidal B-spline (PSB)
      deformation model also enforces smoothness across and can compute strain at the
      apex. The PSB reconstruction algorithm was evaluated on a previously published
      data set to allow head-to-head comparison of the PSB model with existing LV
      deformation reconstruction methods. We conclude that the PSB method can
      accurately reconstruct deformation and strain in the LV wall from tagged MR
      images and has several advantages relative to existing techniques.

PMID- 16424580
TI  - Investigation of a scanned cylindrical ultrasound system for breast hyperthermia.
AB  - This paper investigates the feasibility of a scanned cylindrical ultrasound
      system for producing uniform heating from the central to the superficial portions
      of the breast or localized heating within the breast at a specific location. The
      proposed system consists of plane ultrasound transducer(s) mounted on a scanned
      cylindrical support. The breast was immersed in water and surrounded by this
      system during the treatment. The control parameters considered are the size of
      the transducer, the ultrasound frequency, the scan angle and the shifting
      distance between the axes of the breast and the system. Three-dimensional
      acoustical and thermal models were used to calculate the temperature
      distribution. Non-perfused phantom experiments were performed to verify the
      simulation results. Simulation results indicate that high frequency ultrasound
      could be used for the superficial heating, and the scan angle of the transducer
      could be varied to obtain an appropriate high temperature region to cover the
      desired treatment region. Low frequency ultrasound could be used for deep heating
      and the high temperature region could be moved by shifting the system. In
      addition, a combination of low and high frequency ultrasound could result in a
      portion treatment from the central to the superficial breast or an entire breast
      treatment. Good agreement was obtained between non-perfused experiments and
      simulation results. The findings of this study can be used to determine the
      effects of the control parameters of this system, as well as to select the
      optimal parameters for a specific treatment.

PMID- 16424581
TI  - Theoretical predictions of harmonic generation from submicron ultrasound contrast
      agents for nonlinear biomedical ultrasound imaging.
AB  - Submicron ultrasound contrast agents have aroused attention for their significant
      promise in ultrasonic contrast/molecular imaging, targeted therapy and echo
      particle imaging velocimetry. However, nonlinear acoustic properties of submicron
      encapsulated gas bubbles for ultrasonic applications are still not clearly
      understood. In this paper, nonlinear acoustic emission characteristics from
      submicron bubbles were examined using a numerical study. The modified RP equation
      incorporating viscosity, acoustic radiation, thermal effects and encapsulated
      shell was used to study single bubble dynamics. Further, a size integration
      method, shown previously to be useful in prediction of backscatter spectra from
      groups of bubbles, was applied to analyse response from a bubble population. We
      show that bubbles with radii (200-500 nm) produce significant subharmonic and
      ultraharmonic components of the backscatter spectrum, while smaller bubbles (<200
      nm) provide substantial second harmonic components. Additionally, nanoscale
      bubbles (<100 nm) produce very low backscatter amplitudes and thus may not be
      useful with the use of current ultrasound technology. Analysing optimal
      ultrasound driving pressures and bubbles size ranges for maximal subharmonic and
      ultraharmonic signals showed that sub and ultraharmonic mode nonlinear imaging
      methods may be potentially competitive for larger size bubbles (>200 nm) in
      providing proper contrast-to-tissue signal ratios.

PMID- 16424582
TI  - Comparison of region-of-interest analysis and human observers in the diagnosis of
      Parkinson's disease using [99mTc]TRODAT-1 and SPECT.
AB  - This study determined the relative accuracy of diagnosis of Parkinson's disease
      (PD) using SPECT imaging data, comparing a semi-quantitative region-of-interest
      (ROI) approach and human observers. A set of patients with PD and normal healthy
      control subjects were studied using the dopamine transporter tracer
      [(99m)Tc]TRODAT-1 and SPECT. The sample comprised 81 patients (mean age +/- SD,
      63.4 +/- 10.4 years; age range, 39.0-84.2 years) and 94 healthy controls (mean
      age +/- SD, 61.8 +/- 11.0 years; age range, 40.9-83.3 years). A standardized
      template containing six ROIs was transposed onto subregions of the brain, and the
      ratio of striatal to background ROI values was used as a semi-quantitative
      outcome measure. All images were used in a human observer study, with four
      experienced investigators. The data from the observer and ROI studies were
      analysed using a receiver operating characteristic (ROC) analysis, where the area
      under the ROC curve (AUC) indicated the diagnostic accuracy. ROI analysis and
      human observers gave similar diagnostic performance (mean observer AUC = 0.89,
      best ROI AUC = 0.90). This suggested that the human observers are visually
      acquiring similar information from the images that are contained in the semi
      quantitative striatal uptake.

PMID- 16424583
TI  - Physical evaluation of CT scan methods for radiation therapy planning: comparison
      of fast, slow and gating scan using the 256-detector row CT scanner.
AB  - Although slow-rotation CT scanning (slow-scan CT: SSCT) has been used for
      radiation therapy planning, based on the rationale that the average duration of
      the human respiratory cycle is 4 s, a number of physical and quantitative
      questions require answering before it can be adopted for clinical use. This study
      was performed to evaluate SSCT physically in comparison with other scan methods,
      including respiratory-gated CT (RGCT), and to develop procedures to improve
      treatment accuracy. Evaluation items were geometrical accuracy, volume accuracy,
      water equivalent length and dose distribution using the 256-detector row CT with
      three scan methods. Fast-scan CT (FSCT) was defined as obtaining all respiratory
      phases in cine scan mode at 1.0 s per rotation. FSCT-ave was the averaged FSCT
      images in all respiratory phases, obtained by reconstructing short time
      intervals. SSCT has been defined as scanning with slow gantry rotation to capture
      the whole respiratory cycle in one rotation. RGCT was scanned at the most stable
      point in the respiratory cycle, which provides the same image as that by FSCT at
      the most stable point. Results showed that all evaluation items were dependent on
      motion characteristics. The findings of this study indicate that 3D planning
      based solely on SSCT under free breathing may result in underdosing of the target
      volume and increase toxicity to surrounding normal tissues. Of the three methods,
      RGCT showed the best ability to significantly increase the accuracy of dose
      distribution, and provided more information to minimize the margins. FSCT-ave is
      a satisfactory radiotherapy planning alternative if RGCT is not available.

PMID- 16424584
TI  - Validation of a personalized dosimetric evaluation tool (Oedipe) for targeted
      radiotherapy based on the Monte Carlo MCNPX code.
AB  - Dosimetric studies are necessary for all patients treated with targeted
      radiotherapy. In order to attain the precision required, we have developed
      Oedipe, a dosimetric tool based on the MCNPX Monte Carlo code. The anatomy of
      each patient is considered in the form of a voxel-based geometry created using
      computed tomography (CT) images or magnetic resonance imaging (MRI). Oedipe
      enables dosimetry studies to be carried out at the voxel scale. Validation of the
      results obtained by comparison with existing methods is complex because there are
      multiple sources of variation: calculation methods (different Monte Carlo codes,
      point kernel), patient representations (model or specific) and geometry
      definitions (mathematical or voxel-based). In this paper, we validate Oedipe by
      taking each of these parameters into account independently. Monte Carlo
      methodology requires long calculation times, particularly in the case of voxel
      based geometries, and this is one of the limits of personalized dosimetric
      methods. However, our results show that the use of voxel-based geometry as
      opposed to a mathematically defined geometry decreases the calculation time two
      fold, due to an optimization of the MCNPX2.5e code. It is therefore possible to
      envisage the use of Oedipe for personalized dosimetry in the clinical context of
      targeted radiotherapy.

PMID- 16424585
TI  - Synchronized moving aperture radiation therapy (SMART): improvement of breathing
      pattern reproducibility using respiratory coaching.
AB  - Recently, at Massachusetts General Hospital (MGH) we proposed a new treatment
      technique called synchronized moving aperture radiation therapy (SMART) to
      account for tumour motion during radiotherapy. The basic idea of SMART is to
      synchronize the moving radiation beam aperture formed by a dynamic multileaf
      collimator with the tumour motion induced by respiration. The two key
      requirements for being able to successfully use SMART in clinical practice are
      the precise and fast detection of tumour position during the simulation/treatment
      and the good reproducibility of the tumour motion pattern. To fulfil the first
      requirement, an integrated radiotherapy imaging system is currently being
      developed at MGH. The results of a previous study show that breath coaching
      techniques are required to make SMART an efficient technique in general. In this
      study, we investigate volunteer and patient respiratory coaching using a
      commercial respiratory gating system as a respiration coaching tool. Five healthy
      volunteers, observed during six sessions, and 33 lung cancer patients, observed
      during one session when undergoing 4D CT scans, were investigated with audio and
      visual promptings, with free breathing as a control. For all five volunteers,
      breath coaching was well tolerated and the intra- and inter-session
      reproducibility of the breathing pattern was greatly improved. Out of 33
      patients, six exhibited a regular breathing pattern and needed no coaching, four
      could not be coached at all due to the patient's medical condition or had
      difficulty following the instructions, 13 could only be coached with audio
      instructions and 10 could follow the instructions of and benefit from audio-video
      coaching. We found that, for all volunteers and for those patients who could be
      properly coached, breath coaching improves the duty cycle of SMART treatment.
      However, about half of the patients could not follow both audio and video
      instructions simultaneously, suggesting that the current coaching technique
      requires improvements.

PMID- 16424586
TI  - Dosimetry limitations and a dose correction methodology for step-and-shoot IMRT.
AB  - For the step-and-shoot intensity-modulated radiation therapy (IMRT) technique,
      the combination of high dose rate, multiple beam segments and low dose per
      segment can lead to significant differences between the planned dose and the dose
      delivered to the patient. In this technique, a dose delivery inaccuracy known as
      the 'overshoot' effect is caused by the dose servo control system. This typically
      occurs in the first and last beam segments and causes an over- and underdose,
      respectively. Some dose positional error in the segment sequence is also possible
      there. Commercial ionization chambers (RK-type) and radiographic Kodak films were
      used for the measurements. The reported results were obtained using the
      Pinnacle(3)-V6.2 treatment planning system and a Varian Clinac 21 EX linear
      accelerator equipped with a 120-leaf Millennium MLC. The dose inaccuracy
      measurements were based on the comparison of the dose and profiles for reference
      fields and fields irradiated with the step-and-shoot technique. For our linear
      accelerators, an 'overshoot' effect ranging from 0.1 to 0.6 MU was found,
      corresponding to a dose rate from 100 to 600 MU min(-1), respectively. For
      segments with off-axis distances from 0 to 5.5 cm with >3.5 MU per segment and
      all dose rates, a MLC leaf-position error of <1 mm was measured. For segments
      with an off-axis distance of 9.5 cm, a positional error >2 mm was measured for
      600 MU min(-1) and 1 MU per segment. The purpose of this study was to find a
      correction method for segmental dose errors caused by the 'overshoot' effect when
      small monitor unit and high dose rate are used. To better represent the
      fluctuation of the segment doses in the beam, a dose ratio between reference and
      step-and-shoot irradiated fields was defined. A method for the correction of
      segment dose inaccuracies and a quality assurance programme for the 'overshoot'
      effect were developed. The ordering of the biggest segment shape in the segment
      sequence was studied for ten randomly selected prostate patients planned for
      IMRT. The results of this work can be used to improve the agreement between the
      planned and delivered doses for IMRT.

PMID- 16424587
TI  - The fundamental radiation properties of normoxic polymer gel dosimeters: a
      comparison between a methacrylic acid based gel and acrylamide based gels.
AB  - Polymer gel dosimeters offer a wide range of applications in the three
      dimensional verification of complex dose distributions such as in intensity
      modulated radiotherapy. One of the major difficulties with polymer gel dosimeters
      is their sensitivity to oxygen, as oxygen inhibits the radiation-induced
      polymerization reaction. For several years, oxygen was removed from the gels by
      bubbling the sol with inert gases for several hours during the gel fabrication.
      Also, the gel had to be poured in containers with low oxygen permeability and
      solubility. Recently, it was found that these technical difficulties can easily
      be solved by adding an antioxidant to the gel. These gels are called 'normoxic'
      gels as they can be produced under normal atmospheric conditions. In this study
      several properties of polymer gel dosimeters have been investigated: the dose
      sensitivity, the temporal and spatial stability of the gel, the sensitivity of
      the dose response to temperature during irradiation and during MR imaging, the
      energy dependence and the dose-rate dependence. This study reveals that the
      normoxic polymer gel dosimeter based on methacrylic acid (nMAG) studied in this
      work has inferior radiation properties as compared to the polyacrylamide gelatine
      (PAG) gel dosimeters. It is shown that from the three different gel dosimeters
      investigated in this study, the nPAG gel dosimeter results in a less sensitive
      gel dosimeter but with superior radiation properties as compared to the nMAG gel
      dosimeter. The importance of investigating relevant radiation properties of gel
      dosimeters apart from the radiation sensitivity-prior to their use for dosimetric
      validation experiments-is illustrated and emphasized throughout this study. Other
      combinations of monomer and gelling agent may result in more reliable normoxic
      polymer gel dosimeters.

PMID- 16424588
TI  - Deterministic model for dose calculation in photon radiotherapy.
AB  - We present a model for dose calculation in photon radiotherapy based on
      deterministic transport equations. The model consists of two coupled equations,
      one for photon and one for electron transport and an equation for the absorbed
      dose. No assumptions are made with respect to the geometry or the homogeneity of
      the irradiated medium, so irradiation of any heterogenous medium can be
      simulated. To get a mathematically simpler model, approximations to the exact
      equations are presented which keep the essential physical contents of the exact
      equations, but which can be solved with less numerical effort. The results of
      dose calculations for simple examples are presented and discussed.

PMID- 16424589
TI  - Neutron production from a mobile linear accelerator operating in electron mode
      for intraoperative radiation therapy.
AB  - Intraoperative electron beam radiotherapy is increasingly performed using mobile
      linac delivering therapeutic radiation doses in unshielded operating rooms. While
      no special neutron-shielding problem should arise for operation at 10 MeV or
      less, it is not clear whether this holds true for operation at higher energies.
      This paper reports the measured neutron production from a Mobetron mobile
      electron linac, operated at 12 MeV, and compares the results with those from a
      conventional linac, also operated at 12 MeV in electron mode. Neutron leakage
      measurements were performed by means of passive bubble detectors in the
      scattering foil, patient and floor planes. Neutron dose equivalent rates per unit
      of electron dose delivered by the Mobetron at its normal treatment distance (50
      cm SSD) were 0.33 microSv Gy(-1) at the accelerator head, 0.18 microSv Gy(-1) in
      the patient plane at 15 cm from the beam axis and 0.31 microSv Gy(-1) at the
      floor plane, on the beam axis and under the beam stopper. For a weekly workload
      of 250 Gy, the weekly neutron dose equivalents at 12 MeV for the Mobetron at a
      distance of 300 cm from the scattering foil were 14.3 and 1.7 microSv/week for
      floor below and adjoining areas on the same floor, respectively. Neutron dose
      equivalent rates generated from Mobetron are at least one order of magnitude
      lower than ones produced by a conventional linac operated at the same energy in
      electron mode. Mobetron can be used at 12 MeV in an unshielded operating room for
      a weekly workload of up to 250 Gy if the bremsstrahlung x-rays are shielded to
      negligible levels.

PMID- 16424590
TI  - Measurement of the absolute optical properties and cerebral blood volume of the
      adult human head with hybrid differential and spatially resolved spectroscopy.
AB  - A hybrid differential and spatially resolved spectroscopy (SRS) technique has
      been developed to measure absolute absorption coefficient (mu(a)), reduced
      scattering coefficient (mu'(s)) and cerebral blood volume (CBV) in the adult
      human head. A spectrometer with both differential and SRS capabilities has been
      used to carry out measurements in 12 subjects. Two versions of the calculation
      have been considered using the hybrid technique, with one considering water as a
      chromophore as well as oxy- and deoxy-haemoglobin, and one ignoring water. The
      CBV has also been measured using a previously described technique based on
      changing the arterial saturation (SaO(2)) measured separately by a pulse
      oximeter, resulting in mean +/- SD CBV(a) (intra-individual coefficient of
      variation) = 2.22 +/- 1.06 ml/100 g (29.9%). (The superscript on CBV indicates
      the different calculation basis.) Using the hybrid technique with water ignored,
      CBV(0) = 3.18 +/- 0.73 ml/100 g (10.0%), mu(0)(a)(813 nm) = 0.010 +/- 0.003 mm(
      1) and mu'(0)(s)(813 nm) = 1.19 +/- 0.55 mm(-1) (data quoted at 813 nm). With
      water considered, CBV(w) = 3.05 +/- 0.77 ml/100 g (10.5%), mu(w)(a)(813 nm) =
      0.010 +/- 0.003 mm(-1) and mu'(w)(s)(813 nm) = 1.28 +/- 0.56 mm(-1). The mean
      biases between CBV(0)/CBV(w), CBV(0)/CBV(a) and CBV(w)/CBV(a) are 0.14 +/- 0.09,
      0.79 +/- 1.22 and 0.65 +/- 1.24 ml/100 g. The mean biases between mu(0)(a)(813
      nm)/mu(w)(a)(813 nm) and mu'(0)(s)(813 nm)/mu'(w)(s)(813 nm) are (5.9 +/- 10.0) x
      10(-4) mm(-1) and -0.084 +/- 0.266 mm(-1), respectively. The method we describe
      extends the functionality of the current SRS instrumentation.

PMID- 16424591
TI  - Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered
      construct in vitro.
AB  - Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue
      engineered constructs. Measurements of the developing tissue's MR relaxation
      times (T(1) and T(2)), apparent diffusion coefficient (ADC) and elastic shear
      modulus were conducted over a 4-week growth period using an 11.74 T Bruker
      spectrometer with an imaging probe adapted for MR elastography (MRE). Both the
      relaxation times and the ADC show a statistically significant decrease after only
      one week of tissue development while the tissue stiffness increases progressively
      during the first two weeks of in vitro growth. The measured MR parameters are
      correlated with histologically monitored osteogenic tissue development. This
      study shows that MRM can provide quantitative data with which to characterize the
      growth and development of tissue-engineered bone.

PMID- 16424592
TI  - Site-matched assessment of structural and tissue properties of cortical bone
      using scanning acoustic microscopy and synchrotron radiation muCT.
AB  - 200 MHz scanning acoustic microscopy (SAM) and synchrotron radiation muCT (SR
      muCT) were used to assess microstructural parameters and tissue properties in
      site-matched regions of interest in cortical bone. Anterior and postero-lateral
      regions of ten cross sections from human cortical radius were explored.
      Structural parameters, including diameter and number of Haversian canals per
      cortical area (Ca.Dm, N.Ca/Ar) and porosity Po were assessed with both methods
      using a custom-developed image fusion and analysis software. Acoustic impedance Z
      and degree of mineralization of bone DMB were extracted separately for osteonal
      and interstitial tissues from the fused images. Structural parameter estimations
      obtained from radiographic and acoustic images were almost identical. DMB and
      impedance values were in the range between 0.77 and 1.28 g cm(-3) and 5.13 and
      12.1 Mrayl, respectively. Interindividual and regional variations were observed,
      whereas the strongest difference was found between osteonal and interstitial
      tissues (Z: 7.2 +/- 1.1 Mrayl versus 9.3 +/- 1.0 Mrayl, DMB: 1.06 +/- 0.07 g cm(
      3) versus 1.16 +/- 0.05 g cm(-3), paired t-test, p < 0.05). Weak, but significant
      correlations between DMB and Z were obtained for the osteonal (R(2) = 0.174, p <
      10(-4)) and for the pooled (osteonal and interstitial) data. The regression of
      the pooled osteonal and interstitial tissue data follows a second-order
      polynomial (R(2) = 0.39, p < 10(-4)). Both modalities fulfil the requirement for
      a simultaneous evaluation of cortical bone microstructure and material properties
      at the tissue level. While SAM inspection is limited to the evaluation of
      carefully prepared sample surfaces, SR-muCT provides volumetric information on
      the tissue without substantial preparation requirements. However, SAM provides a
      quantitative estimate of elastic properties at the tissue level that cannot be
      captured by SR-muCT.

PMID- 16424593
TI  - Derivation of elastic stiffness from site-matched mineral density and acoustic
      impedance maps.
AB  - 200 MHz acoustic impedance maps and site-matched synchrotron radiation micro
      computed tomography (SR-muCT) maps of tissue degree of mineralization of bone
      (DMB) were used to derive the elastic coefficient c(33) in cross sections of
      human cortical bone. To accomplish this goal, a model was developed to relate the
      DMB accessible with SR-muCT to mass density. The formulation incorporates the
      volume fractions and densities of the major bone tissue components (collagen,
      mineral and water), and accounts for tissue porosity. We found that the mass
      density can be well modelled by a second-order polynomial fit to DMB (R(2) =
      0.999) and appears to be consistent with measurements of many different types of
      mineralized tissues. The derived elastic coefficient c(33) correlated more
      strongly with the acoustic impedance (R(2) = 0.996) than with mass density (R(2)
      = 0.310). This finding suggests that estimates of c(33) made from measurements of
      the acoustic impedance are more reliable than those made from density
      measurements. Mass density and elastic coefficient were in the range between 1.66
      and 2.00 g cm(-3) and 14.8 and 75.4 GPa, respectively. Although SAM inspection is
      limited to the evaluation of carefully prepared sample surfaces, it provides a
      two-dimensional quantitative estimate of elastic tissue properties at the tissue
      level.

PMID- 16424595
TI  - Protein microarrays: a new tool for profiling antibody cross-reactivity.
AB  - Antibody cross-reactivity can compromise interpretation of experiments and derail
      therapeutic antibody development. Standard techniques such as
      immunohistochemistry or Western analysis provide important but often inadequate
      approaches to assess antibody specificity. Protein microarrays are providing a
      new approach to rapidly characterize antibody cross-reactivity against 1,000s of
      proteins simultaneously. This review will focus on reported examples of antibody
      cross-reactivity, methods used to characterize them, and the recent development
      and use of protein microarrays for assessing antibody specificity.

PMID- 16424594
TI  - Production and characterization of monoclonal antibodies against human IgG in
      Balb/c mouse.
AB  - Immunoglobulin G (IgG) is the main immunoglobulin in natural human serum. It
      constitutes 70 to 75 percent of all immunoglobulins. Monoclonal antibodies have
      many applications in diagnosis, treatment and purification. The conjugated
      monoclonal antibodies against human IgG are used in most diagnostic kits. For
      production of monoclonal antibodies against human IgG, spleen cells of the most
      immune mouse were fused with SP2/0 (myeloma cells) using Poly Ethylene Glycol
      (PEG). Supernatant of hybridoma cells was screened for detection of antibody by
      ELISA. The suitable clones were selected for limiting dilution (L.D). Then, the
      supernatant of suitable monoclones were assessed for cross reactivity with IgM &
      IgA by ELISA and confirmed by immunobloting. The subclasses of the selected
      monoclonal antibodies were determined and the clones were frozen and kept in
      liquid nitrogen. Finally, suitable monoclone was injected into the mouse,
      intraperitoneally, that has been primed with Pristane. In this study, 127 clones
      were obtained of which 15 clones had absorbance more than 1 which two of them
      with absorbance about 1.5 were selected for limiting dilution. The yield of
      limiting dilution was 6 clones with absorbance about 1.8 which did not show cross
      reactivity with IgM & IgA. Among these clones, G2 monoclone with IgG1 subclass
      was selected as suitable one and it was reproduced in FCS free RPMI 1640. For
      large scale production in invivo, the suitable clone was implanted in the
      peritoneum of the Balb/c mouse and its titer was measured, which showed 1/100,000
      dilution for ascitic fluid, having no cross reactivity with IgM & IgA. Monoclonal
      antibody was purified by chromatography, confirmed by SDS- PAGE, conjugated with
      enzyme and applied for diagnostic kits.

PMID- 16424596
TI  - Production of monoclonal antibody against alkaline phosphatase.
AB  - BACKGROUND: Monoclonal antibody against alkaline phosphatase (Alp) has many
      applications which Alp-anti Alp complex (APAAP) formation is one of the most
      important ones. This complex is applicable in many immunohistochemical and
      immunocytochemical techniques such as diagnosis of various kinds of leukemias,
      lymphomas, skin diseases, kidney dysfunctions, etc. OBJECTIVE: Production of anti
      Alp monoclonal antibody for utilization in APAAP complex. METHODS: After several
      arranged injections of Alp to Balb/c mice and determining the specific antibody
      titer by ELISA test, the spleen lymphocytes of immunized mice and Sp2/0 myeloma
      cells were fused using polyethylene glycol as fusing agent and hybridoma cells
      were cultured in HAT medium. Identification and selection of anti-Alp producing
      clones were done by performing ELISA test on supernatants of all resulting
      clones. Limiting dilution method was used to attain monoclones and the effect of
      obtained antibodies on enzyme activity was investigated by a specific ELISA test.
      For production of concentrated Ab, the hybridoma cells were injected to
      peritoneal cavity of mice and the produced ascetic fluids were collected. Finally
      class and subclass of the obtained antibodies were determined by Isostrip kit.
      RESULTS: After six rounds of fusion, 104 Hybridoma clones were obtained and two
      Anti-Alp producing clones (A_1G_8 and A_1G_9) were selected and subcloned. Both
      antibodies were IgG_1 with kappa (kappa) light chains. These antibodies did not
      affect the enzyme activity and the electrophoresis of ascetic fluids showed an
      obvious band in gamma (gamma) position. CONCLUSION: Because these antibodies are
      from IgG class and don't affect the enzyme activity, it seems that they are
      suitable for APAAP complex formation.

PMID- 16424597
TI  - Surveillance of natural acquired antibodies to Haemophilus influenzae type b
      among children in Cairo-Egyptian.
AB  - In Egypt, the incidence of invasive Haemophilus influenzae type b (Hib) disease
      is not common and the vaccine is still not included into the national
      immunization program. The aim of this study was to evaluate the natural immunity
      to Hib in healthy children at Egyptian capitol (Cairo). One hundred and two
      children were enrolled in our study of age one month to 15 year. Anti-capsular
      polysaccharide (PRP) of Hib specific IgM and IgG antibody concentrations were
      estimated using enzyme immunoassay. The majority (64.7%, 75.5%) of children had a
      protective levels>or=15 microg/ml of specific antibodies (IgM and IgG).
      Fortunately, a total of 95.5% of the children under 5 years old had a protective
      level. Our result will provide evidence that in Egypt capitol, the natural
      immunity against Hib can be acquired at an early age.

PMID- 16424598
TI  - Generation of mouse-human hybridomas secreting human monoclonal antibodies to
      Japanese cedar pollen allergen Cry j1.
AB  - Peripheral blood lymphocytes from 13 donors were transformed with Epstein-Barr
      virus (EBV) to establish immortalized human B-cells secreting antibodies to
      Japanese cedar (Cryptomeria japonica) pollen allergens. EBV-transformed B
      lymphocytes were then fused with mouse myeloma SP2/O3, and three clones of mouse
      human hybridomas secreting human IgM class monoclonal antibodies to a cedar
      pollen allergen Cry j1 were established.

PMID- 16424599
TI  - Monoclonal and recombinant antibodies, 30 years after ...
AB  - In 1975, the hybridoma technology provided, for the first time, an access to
      murine monoclonal antibodies. During the two following decades, their high
      potential, as laboratory tools, was rapidly exploited, but in vivo applications
      were still very limited. Nowadays, antibodies, omnipresent in both diagnostic and
      research domains, are largely invading the domain of therapy. A wide array of
      novel technologies, including phage display and transgenic mice, to isolate fully
      human antibodies and engineer these molecules, has been implemented. The natural
      propensity, of the antibody molecules, to metamorphosis makes them an ideal
      response to new applications and therapeutic challenges. The present review is a
      tentative update of the different antibody "formats" and a walk through the
      techniques recently applied to antibody engineering. In addition it also
      addresses some specific issues such as the development of expression systems
      suitable for large-scale production of recombinant antibodies.

PMID- 16424602
TI  - EuroGentest standing up to scrutiny--first year demonstrates good progress
      harmonizing community approaches.

PMID- 16424603
TI  - QTL mapping of Fusarium moniliforme ear rot resistance in maize. 1. Map
      construction with microsatellite and AFLP markers.
AB  - To map the QTLs of Fusarium moniliforme ear rot resistance in Zea mays L., a
      total of 230 F2 individuals, derived from a single cross between inbred maize
      lines R15 (resistant) and Ye478 (susceptible), were genotyped for genetic map
      construction using simple sequence repeat (SSR) markers and amplified fragment
      length polymorphism (AFLP) markers. We used 778 pairs of SSR primers and 63
      combinations of AFLP primers to detect the polymorphisms between parents, R15 and
      Ye478. From the polymorphic 30 AFLP primer combinations and 159 SSR primers, we
      scored 260 loci in the F2 population, among which 8 SSR and 13 AFLP loci could
      not be assigned to any of the linkage groups. An integrated molecular genetic
      linkage map was constructed by the remaining 151 SSR and 88 AFLP markers, which
      distributed throughout the 10 linkage groups of maize and spanned the genome of
      about 3463.5 cM with an average of 14.5 cM between two markers. On 4 chromosomes,
      we detected 5 putative segregation distortion regions (SDRs), including 2 new
      ones (SDR2 and SDR7). The other 3 SDRs were located near the regions where
      gametophyte genes were mapped, indicating that segregation distortion could be
      partially caused by gametophytic factors.

PMID- 16424604
TI  - Tissue-culture-responsive and autotetraploidy-responsive changes in metabolic
      profiles of cucumber (Cucumis sativus L.).
AB  - Somaclonal variation commonly occurs during in vitro plant regeneration and may
      introduce unintended changes in numerous plant characters. In order to assess the
      range of tissue-culture-responsive changes on the biochemical level, the
      metabolic profiles of diploid and tetraploid cucumber R1 plants regenerated from
      leaf-derived callus were determined. Gas chromatography and mass spectrometry
      were used for monitoring of 48 metabolites and many significant changes were
      found in metabolic profiles of these plants as compared to a seed-derived
      control. Most of the changes were common to diploids and tetraploids and were
      effects of tissue culture. However, tetraploids showed quantitative changes in 14
      metabolites, as compared to regenerated diploids. These changes include increases
      in serine, glucose-6P, fructose-6P, oleic acid and shikimic acid levels. Basing
      on this study we conclude that the variation in metabolic profiles does not
      correlate directly with the range of genome changes in tetraploids.

PMID- 16424605
TI  - Identification of QTLs associated with citrus resistance to Phytophthora
      gummosis.
AB  - Citrus gummosis, caused by Phytophthora spp., is an important citrus disease in
      Brazil. Almost all citrus rootstock varieties are susceptible to it to some
      degree, whereas resistance is present in Poncirus trifoliata, a closely related
      species. The objective of this study was to detect QTLs linked to citrus
      Phytophthora gummosis resistance. Eighty individuals of the F1 progeny, obtained
      by controlled crosses between Sunki mandarin Citrus sunki (susceptible) and
      Poncirus trifoliata cv. Rubidoux (resistant), were evaluated. Resistance to
      Phytophthora parasitica was evaluated by inoculating stems of young plants with a
      disc of fungal mycelia and measuring lesion lengths a month later. Two QTLs
      linked to gummosis resistance were detected in linkage groups 1 and 5 of the P.
      trifoliata map, and one QTL in linkage group 2 of the C. sunki map. The
      phenotypic variation explained by individual QTLs was 14% for C. sunki and ranged
      from 16 to 24% for P. trifoliata. The low character heritability (h2 = 18.7%) and
      the detection of more than one QTL associated with citrus Phytophthora gummosis
      resistance showed that inheritance of the resistance is quantitative.

PMID- 16424606
TI  - Genetic parameters and correlations of collar rot resistance with important
      biochemical and yield traits in opium poppy (Papaver somniferum L.).
AB  - Collar rot, caused by Rhizoctonia solani Kuhn, is one of the most severe fungal
      diseases of opium poppy. In this study, heritability, genetic advance and
      correlation for 10 agronomic, 1 physiological, 3 biochemical and 1 chemical
      traits with disease severity index (DSI) for collar rot were assessed in 35
      accessions of opium poppy. Most of the economically important characters, like
      seed and capsule straw yield per plant, oil and protein content of seeds,
      peroxidase activity in leaves, morphine content of capsule straw and DSI for
      collar rot showed high heritability as well as genetic advance. Highly
      significant negative correlation between DSI and seed yield clearly shows that as
      the disease progresses in plants, seed yield declines, chiefly due to premature
      death of infected plants as well as low seed and capsule setting in the survived
      population of susceptible plants. Similarly, a highly significant negative
      correlation between peroxidase activity and DSI indicated that marker-assisted
      selection of disease-resistant plants based on high peroxidase activity would be
      effective and survived susceptible plants could be removed from the population to
      stop further spread.

PMID- 16424608
TI  - Polymorphism of beta-lactoglobulin gene in Indian goats and its effect on milk
      yield.
AB  - Polymorphism in the beta-LG gene in the Indian goat was investigated by the SDS
      PAGE and PCR-RFLP method. SDS-PAGE was carried out in 1098 samples belonging to 8
      different breeds of Indian goats. The electrophoretic pattern in the beta-LG
      locus showed the presence of AA and AB genotypes with frequencies of 0.81 and
      0.19, 0.89 and 0.11, 0.50 and 0.50, 0.80 and 0.20, 0.84 and 0.16, 1.00 and 0.00,
      0.98 and 0.02 and 0.950 and 0.050 in Jamunapari, Barbari, Marwari, Sirohi,
      Jakhrana, Beetal, Local UP and Local MP goats, respectively. A total of 358
      individuals belonging to 13 different genetic groups were analyzed by the PCR
      RFLP method. The amplified product was observed as 426 bp and the restriction
      digestion with SacII revealed three genotypes, namely S1S1, S1S2 and S2S2 at the
      beta-LG locus. The frequency of the S2S2 genotype ranged from 0.42 to 1.00 in the
      population. An analysis was carried out in Jamunapari and Barbari goats to
      observe the effect of the beta-LG genotype on 90-day milk yield. Least squares
      analysis of data showed that beta-LG AA animals had higher milk yield than the
      beta-LG AB genotype in both breeds (P < 0.01).

PMID- 16424609
TI  - Microsatellite polymorphism in intron 1 of the bovine myostatin gene.
AB  - Microsatellites within genes have become important because of their association
      with genetic diseases in humans. A novel microsatellite was identified in the
      first intron of the bovine myostatin gene. It is characterized by a
      mononucleotide core motif that exhibits polymorphic sequence variants (from 12 to
      21 repeats) within and between some bovine breeds. Structural analysis of the
      microsatellite region in bovines as well as in closely related species permitted
      to trace the possible mechanisms for its structural evolution across the order
      Artiodactyla.

PMID- 16424610
TI  - A new SNP in the promoter region of the porcine MYF5 gene has no effect on its
      transcript level in m. longissimus dorsi.
AB  - Myogenic factor 5 (myf-5) is the product of the MYF5 gene, belonging to the MyoD
      family. This transcription factor participates in the control of myogenesis. We
      identified 3 new mutations in the promoter region of the gene: A65C, C580T and
      C613T. The aim of this study was to evaluate the influence of the A65C
      transversion on gene expression. The analysis was conducted on 15 Polish Large
      White gilts. The relative content of MYF5 mRNA in m. longissimus dorsi did not
      differ significantly across MYF5 genotypes (AA, AC, CC). This result suggests
      that the A65C transversion may not play an important role in the expression of
      the MYF5 gene in analysed adult muscle but it abolishes a putative binding site
      for two transcription factors (CDP and HSF1) and creates such a site for Sp1.

PMID- 16424607
TI  - The multigene family of fatty acid-binding proteins (FABPs): function, structure
      and polymorphism.
AB  - Fatty acid-binding proteins (FABPs) are members of the superfamily of lipid
      binding proteins (LBP). So far 9 different FABPs, with tissue-specific
      distribution, have been identified: L (liver), I (intestinal), H (muscle and
      heart), A (adipocyte), E (epidermal), Il (ileal), B (brain), M (myelin) and T
      (testis). The primary role of all the FABP family members is regulation of fatty
      acid uptake and intracellular transport. The structure of all FABPs is similar -
      the basic motif characterizing these proteins is beta-barrel, and a single ligand
      (e.g. a fatty acid, cholesterol, or retinoid) is bound in its internal water
      filled cavity. Despite the wide variance in the protein sequence, the gene
      structure is identical. The FABP genes consist of 4 exons and 3 introns and a few
      of them are located in the same chromosomal region. For example, A-FABP, E-FABP
      and M-FABP create a gene cluster. Because of their physiological properties some
      FABP genes were tested in order to identify mutations altering lipid metabolism.
      Furthermore, the porcine A-FABP and H-FABP were studied as candidate genes with
      major effect on fatness traits.

PMID- 16424611
TI  - Polymorphism within the LDHA gene in the homing and non-homing pigeons.
AB  - A total of 445 domestic pigeons were genotyped for the lactate dehydrogenase
      (LDHA) gene. Crude DNA was isolated from blood samples and feathers. Two
      polymorphic sites were identified in intron 6: one near the splice donor site GT
      is called site H and the other near the splice acceptor site is called site B.
      Interestingly, the nucleotide changes of both these sites associate perfectly
      with the A and B alleles of HaeIII polymorphism: the A allele with nucleotide A
      of site H and nucleotide T of site B; while the B allele with nucleotide G of
      site H and nucleotide G of site B. In this study, we have identified the
      molecular difference between alleles A and B of the pigeon LDHA gene. The
      difference at site H in intron 6 explains the HaeIII polymorphism. The
      frequencies of LDHAAB and LDHABB genotypes between the analysed groups differ
      significantly (P < 0.001); the LDHAA allele was more frequent in the groups of
      pigeons with elevated homing performance (P < 0.001). The functional difference
      may be due to the change at site B, the potential splice branch site. Since LDHA
      activity is associated with the homing ability, it is possible that during the
      process of selection for the homing ability, the LDHAA allele has been selected,
      and is more prevalent in the top-racing groups.

PMID- 16424612
TI  - Mitochondrial DNA mutations in human neoplasia.
AB  - Many models of tumour formation have been put forth so far. In general they
      involve mutations in at least three elements within the cell: oncogenes, tumour
      suppressors and regulators of telomere replication. Recently numerous mutations
      in mitochondria have been found in many tumours, whereas they were absent in
      normal tissues from the same individual. The presence of mutations, of course,
      does not prove that they play a causative role in development of neoplastic
      lesions and progression; however, the key role played by mitochondria in both
      apoptosis and generation of DNA-damaging reactive oxygen species might indicate
      that the observed mutations contribute to tumour development. Recent experiments
      with nude mice have proven that mtDNA mutations are indeed responsible for tumour
      growth and exacerbated ROS production. This review describes mtDNA mutations in
      main types of human neoplasia.

PMID- 16424614
TI  - Mutagenic activity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AB  - MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin, which can
      damage dopaminergic neurons. It causes symptoms resembling those observed in
      patients suffering from Parkinson's disease, and hence this toxin is widely used
      in studies on animal models of this disorder. Mutagenicity of MPTP was also
      reported by some authors, but results obtained by others suggested that this
      compound is not mutagenic. Interestingly, those contrasting results were based on
      the same assay (the Ames test). Therefore, we aimed to test MPTP mutagenicity by
      employing a recently developed Vibrio harveyi assay, which was demonstrated
      previously to be more sensitive than the Ames test, at least for some mutagens.
      We found that MPTP showed a significant mutagenic activity. Moreover, MPTP
      mutagenicity was attenuated by methylxanthines, compounds that are known to form
      complexes with aromatic mutagens.

PMID- 16424613
TI  - A quantitative bacterial micro-assay for rapid detection of serum phenylalanine
      in dry blood-spots: application in phenylketonuria screening.
AB  - Phenylketonuria is an inherited metabolic disease, which is characterized by
      increased level of serum phenylalanine (Phe). The quantitative measurement of Phe
      in the serum is necessary to confirm the disease, and to distinguish
      phenylketonuria from other forms of hyperphenylalaninemia. In this study, we
      report a rapid and inexpensive micro-assay for simultaneous detection and
      quantitative measurement of serum Phe in dry blood-spots. Analysis of the
      standard curve showed a broad linear Phe range of 120-1800 micromol L(-1).
      Application of this method in conjunction with the standard Guthrie bacterial
      inhibition assay and high-pressure liquid chromatography in analyzing 34 samples
      from phenylketonuria patients and control samples produced comparable results,
      with the regression equation of Y= 0.994X + 0.996. The advantage of this method
      over the Guthrie bacterial inhibition assay is its ability to measure the serum
      Phe quantitatively without false positive results. The method was successfully
      applied to dried blood-spots as well as serum and whole blood samples. The cost
      per sample is about 20-50 US cents, which is much less than those of high
      pressure liquid chromatography and enzymatic commercial kits. The method can be
      automated, which is suitable for neonatal and mass phenylketonuria screening,
      especially in developing countries, where funding is a limiting factor.

PMID- 16424615
TI  - Infertility and marker chromosomes: application of molecular cytogenetic
      techniques in a case of inv dup(15).
AB  - We report on a phenotypically normal man with infertility, whose 47,XY,+mar
      karyotype was studied by spectral karyotyping (SKY) and fluorescence in situ
      hybridization (FISH) using a chromosome-15-specific probe (LSI SNRPN). By these
      techniques, the marker chromosome was identified as a small inv dup (15).
      Possible causes for male infertility in this case are discussed.

PMID- 16424617
TI  - Endoscopic and histologic findings in Iranian patients with heartburn.
AB  - BACKGROUND: Heartburn is a common manifestation of gastroesophageal reflux
      disease. Barrett's esophagus and esophageal adenocarcinoma, known complications
      of this disease, appear to be less prevalent in Asia than in Western countries.
      We looked for endoscopic and histologic evidence of Barrett's esophagus in
      Iranian patients with heartburn. METHODS: During September 2001 to September
      2003, endoscopy was done in all patients with heartburn, either lasting longer
      than 3 months (n=1182) or for 1-3 months but resistant to 4 weeks of omeprazole
      therapy (n=66). Biopsy was taken from columnar-lined mucosa above the GE
      junction, at 5 cm above the Z line in normal- appearing mucosa, and from any
      abnormal areas. RESULTS: Of the 1248 patients (mean age 45 [SD 15.5] years, 750
      men; duration of heartburn 68 [SD 87.5] months), 960 (66.5%) had erosive
      esophagitis and 30 (2.4%) had Barrett's esophagus, including 10 and 20 with long-
      and short-segment involvement, respectively. Of 134 patients with normal
      appearing mucosa, 122 had histologic evidence of esophagitis. CONCLUSION:
      Barrett's esophagus may be less common in Iran than in Western countries, despite
      presence of severe heartburn and erosive esophagitis.

PMID- 16424616
TI  - Prophylactic portasystemic shunt in non-cirrhotic portal fibrosis: is it
      worthwhile? Nobody knows.

PMID- 16424619
TI  - Prophylactic surgery in non-cirrhotic portal fibrosis:is it worthwhile?
AB  - BACKGROUND: In cirrhotic patients with portal hypertension prophylactic
      portasystemic shunts have been found to be ineffective as deaths from post-shunt
      liver failure exceed those from bleeding. However, in patients with non-cirrhotic
      portal hypertension, variceal bleeding rather than liver failure is the common
      cause of death. In developing countries shortage of tertiary health-care
      facilities and blood banks further increases mortality due to variceal bleed.
      AIM: To study the results of prophylactic operations to prevent variceal bleeding
      in patients with portal hypertension due to non-cirrhotic portal fibrosis (NCPF).
      METHODS: Between 1976 and 2001, we performed 45 prophylactic operations in
      patients with NCPF, if the patients had high-risk esophagogastric varices or
      symptomatic splenomegaly and hypersplenism. Proximal lienorenal shunt was done in
      41 patients and the remaining underwent splenectomy with (2 patients) or without
      (2 patients) devascularization. RESULTS: There was no operative mortality. Thirty
      eight patients were followed up for a mean 49 (range, 12-236) months. Three
      patients bled - one was variceal and two due to duodenal ulcers; none died of
      bleeding. There were 2 late deaths (6 weeks and 10 years after surgery), one from
      an unknown cause and one due to chronic renal failure. The delayed morbidity was
      47%. This included 7 patients who developed portasystemic encephalopathy, 4
      glomerulonephritis, 2 pulmonary arteriovenous fistulae and 5 ascites requiring
      treatment with diuretics. Thus only 20 (53%) patients were symptom-free on follow
      up. CONCLUSIONS: Prophylactic surgery is safe and effective in preventing
      variceal bleeding in NCPF but at the cost of high delayed morbidity.

PMID- 16424620
TI  - Factors determining successful outcome following pneumatic balloon dilation in
      achalasia cardia.
AB  - BACKGROUND: Pneumatic balloon dilation is a popular method of treating patients
      with achalasia cardia. It may be useful to know the factors that predict response
      to this treatment. AIM: To determine predictors of outcome following pneumatic
      balloon dilation in patients with achalasia cardia. METHODS: Records of 62
      patients who had undergone pneumatic dilation using Rigiflex balloon dilators
      (Boston Scientific, Boston, MA, USA) were reviewed. Follow-up data were available
      for 52 patients. Data from patients with and without improvement in symptoms were
      compared. RESULTS: Of the 52 patients (age mean 44 [range 11-68] years; 27 male;
      median symptom duration 20 [4-90] months], 42 (81%) patients had response in
      symptoms after balloon dilatation. On univariate analysis, the responders more
      often had age> 40 years (26/42 [62%] versus 1/10 [10%], p=0.003), and less often
      had lower esophageal sphincter pressure> 50 mmHg (8/10 [80%] versus 10/42 [24%],
      p=0.0007) and mid-esophageal body hypocontraction (7/10 [70%] versus 12/24 [29%]
      p=0.01) than the non-responders. On multivariate analysis only age <or= 40 years
      (p=0.02) was associated with poor outcome. CONCLUSION: Younger age may predict
      non-response to balloon dilation using Rigiflex balloon dilators in patients with
      achalasia cardia.

PMID- 16424618
TI  - Fibrosing colonopathy in a man with cystic fibrosis on pancreatic enzyme
      supplements.

PMID- 16424621
TI  - Subjective global assessment: a simple and reliable screening tool for
      malnutrition among Indians.
AB  - BACKGROUND AND AIMS: Subjective global assessment (SGA) is a simple and reliable
      malnutrition-screening tool. The SGA has not been evaluated in India or in
      populations where chronic energy deficiency (CED) is rampant. We evaluated the
      value of preoperative nutrition, determined using the SGA, in predicting
      postoperative adverse outcomes in cancer patients. METHODS: Two hundred and
      ninety-four cancer patients undergoing elective surgery were screened for
      malnutrition using a modified version of the SGA, and 266 patients (aged 14-73
      years [median 50]; 165 male) were eligible. All patients were followed up till
      discharge, and number of days on antibiotics, length of postoperative stay,
      occurrence of major adverse events, and death within 30 days were recorded. The
      association of preoperative SGA scores (A, B, or C) and BMI groups (< 18.5, 18.5
      20 or> 20 Kg/m2) and four outcome variables were tested for statistical
      significance. RESULTS: The cancer sites included head and neck region in 112,
      gastrointestinal tract in 53, thoracic organs in 28, and other sites in 73
      patients. The SGA scores were A in 152, B in 98, and C in 16 patients. The BMI
      was < 18.5 in 110 (41.8%) patients. The length of postoperative stay and the
      number of antibiotic days revealed a significant trend from SGA-A to SGA-C
      (p=0.000). Pre-defined adverse events occurred in 7.9%, 17.3% and 25% of SGA
      groups A, B, and C, respectively (p=0.025). The risk for adverse events was
      significantly higher in SGA-C group (OR 5.27, 95% CI 1.35-20.51, p< 0.016)
      compared to SGA-A group. Three patients in SGA-B group and one in SGA-C group
      died within 30 days (p=0.04). No significant association was detected between the
      three BMI groups and duration of antibiotic use, length of postoperative stay,
      adverse events or mortality. CONCLUSION: SGA is a simple and inexpensive way to
      identify clinically relevant malnutrition in Indian patients undergoing cancer
      surgery. Low BMI was not associated with postoperative adverse outcomes, and its
      use for nutritional screening is likely to overestimate severe malnutrition in
      Indian patients.

PMID- 16424622
TI  - Vitamin E-based therapy is effective in ameliorating transaminasemia in
      nonalcoholic fatty liver disease.
AB  - BACKGROUND: Comparative trials of ursodeoxycholic acid (UDCA), vitamin E and
      weight management programs among patients with nonalcoholic fatty liver disease
      (NAFLD) are lacking. AIM: To find an effective single agent or combination of
      agents for management of NAFLD. METHODS: In this retrospective study, consecutive
      patient with histologically confirmed NAFLD with raised ALT were included. The
      patients received either weight management (exercise and therapeutic lifestyle
      changes [TLC] diet with a target to reduce body weight 10% in 6 months) (group I)
      ; weight management + UDCA (300 mg BID) (group II); or weight management + UDCA +
      vitamin E (400 mg OD) (group III). Outcome measure was normalization of ALT.
      RESULTS: 42 patients (18, 12 and 12 in groups I, II and III, respectively) were
      included between 1996 and 2004. All patients in group III normalized their ALT
      levels, which was significantly higher than numbers in group I (8/18) and group
      II (5/12); (p=0.003). Post treatment ALT was significantly lower in group III
      (28.6 [9.3]) as compared to group I (59.3 [32.2]) and group II (49.0[31.8]);
      (p=0.01). Type of therapy received was the only factor predictive of ALT
      normalization. CONCLUSION: Combination regimen containing vitamin E appears to be
      effective in normalizing ALT among NAFLD patients.

PMID- 16424623
TI  - Side-to-side aorto-mesenteric anastomosis for management of abdominal angina.
AB  - Abdominal angina and fear of eating are manifestations of mesenteric ischemia.
      This infrequent cause of abdominal pain was diagnosed in a 60-year-old female
      smoker. We performed a novel side-to-side aorto-mesenteric anastomosis for
      mesenteric revascularization, with good short-term (6 months) result.

PMID- 16424624
TI  - Cytomegalovirus involving gastric antrum in immunocompromised hosts: a report of
      5 cases.
AB  - Cytomegalovirus infection, which is common in immunosuppressed patients, only
      rarely affects the stomach, especially the gastric antrum. We report five
      patients with cytomegalovirus infection of the stomach with antral involvement.
      Of these, four had undergone renal transplant and one had HIV infection. All
      patients presented with upper gastrointestinal symptoms that did not respond to
      proton pump inhibitors and prokinetic drugs. In addition, all had systemic
      symptoms. Diagnosis was made at upper GI endoscopy and biopsy, and ganciclovir
      treatment led to improvement.

PMID- 16424625
TI  - Visceral scalloping.

PMID- 16424627
TI  - Carcinoid tumor of bile duct.
AB  - We report a 38-year-old lady with carcinoid tumor of the extrahepatic biliary
      tract who presented with recurrent obstructive jaundice and previous surgery for
      suspected choledocholithiasis. MRCP revealed a large bile duct tumor extending
      from the confluence up to the superior aspect of the pancreas; this was
      completely excised, with bilio-enteric anastomosis. These tumors are
      characteristically slow growing and, therefore, are amenable to aggressive
      surgical excision, which offers the best chance of cure.

PMID- 16424626
TI  - Benign esophageal stricture following aluminium phosphide poisoning.
AB  - Aluminium phosphide is often implicated in accidental and suicidal poisoning in
      India. Ingestion of even half a fresh tablet invariably results in death, whereas
      exposed tablets are usually considered harmless. We report two cases of short
      segment esophageal strictures that occurred following ingestion of exposed tablet
      of aluminium phosphide. Both cases could be successfully managed by endoscopic
      dilatation.

PMID- 16424628
TI  - Thyrotoxicosis co-existing with ulcerative colitis.
AB  - A 32-year-old lady was admitted with complaints of recurrent episodes of vomiting
      and loose stools associated with tenesmus and blood and mucus. She also had a
      neck swelling since 11 years of age, and had features of thyrotoxicosis for five
      to six months. She responded to balsalazide only after her thyroid status was
      controlled with carbimazole.

PMID- 16424629
TI  - Splenic rupture as a complication of colonoscopy.
AB  - Splenic rupture is a rare but potentially lethal complication of colonoscopy. We
      report a 66-year-old man who developed abdominal pain 6 hours after diagnostic
      colonoscopy. His clinical status deteriorated rapidly. Splenic rupture was
      identified at laparotomy. He recovered after surgery.

PMID- 16424630
TI  - Ectopic pancreatic tissue mimicking ampullary tumor.
AB  - Ectopic pancreas is an anomaly in the fusion of the two pancreatic buds where an
      ectopic rest develops at a place away from the normal site. We report a 70-year
      old lady who presented with obstructive jaundice; she was found to have an
      ampullary tumor highly suggestive of malignancy, for which she underwent
      pancreatico-duodenectomy. However, histology showed ectopic pancreatic tissue in
      the ampulla.

PMID- 16424631
TI  - Primary lymph node gastrinoma in jejunal mesentery.
AB  - Primary gastrinomas have been reported in lymph nodes within the gastrinoma
      triangle. We report a 56-year-old woman with possible primary lymph node
      gastrinoma in the jejunal mesentery. Six months after excision of the tumor, she
      is asymptomatic and serum gastrin level is normal.

PMID- 16424632
TI  - Liver function tests in normal pregnancy: a study from southern India.

PMID- 16424633
TI  - Hepatitis B virus infection among Indian tribes: need for vaccination program.

PMID- 16424634
TI  - Association of asthma and allergic rhinitis with celiac disease.

PMID- 16424635
TI  - Pancreatic pseudocysts in brothers: familial, environmental or incidental?

PMID- 16424636
TI  - Small bowel volvulus around feeding jejunostomy tube.

PMID- 16424637
TI  - Cherry pip bezoars causing acute small intestinal obstruction presenting as
      diabetic ketoacidosis.

PMID- 16424638
TI  - Olanzapine-induced diabetes due to pancreatitis.

PMID- 16424639
TI  - Liver cell adenoma with co-existing hepatic granulomas in an HIV-positive
      patient.

PMID- 16424641
TI  - Ortner's syndrome: an unusual cause of hoarse voice.

PMID- 16424640
TI  - Noninvasive ventilation in childhood acute neuromuscular respiratory failure: a
      pilot study.
AB  - BACKGROUND: Over a 36-month study period, 10 nonconsecutive neuromuscular
      pediatric patients (6 infants, mean age 10.16 months, and 4 children, mean age
      9.3 years) presenting with acute respiratory failure (ARF) were treated by
      noninvasive positive pressure ventilation (NPPV). All patients required immediate
      respiratory support and fulfilled our intubation criteria. OBJECTIVE: The aim of
      the study was to verify if early NPPV was able to avoid endotracheal intubation
      and to improve both oxygenation and ventilation within 24 h from admission in
      this clinical setting. PATIENTS AND METHODS: A prospective pilot study was
      carried out on neuromuscular patients admitted to the pediatric intensive care
      unit (PICU) of the Catholic University of Rome because of ARF and managed
      exclusively with NPPV for at least 24 h following admission. All patients were
      treated using a flow-triggered mechanical ventilator through a face mask or using
      the new helmet interface. RESULTS: Eight patients were successfully ventilated
      during the observation period and 2 early failures occurred. Among children
      undergoing face mask NPPV, the PaO(2)/FiO(2) ratio increased from a median value
      of 75 (range 48-149) to 240 (range 133-385; p < 0.001) and 328 (range 180-371; p
      < 0.001) at selected time points (3 and 12 h after NPPV introduction,
      respectively); the alveolar-to-arterial oxygenation difference showed a similar
      trend, i.e. decreasing from a median value of 589 (range 213-659) to 128 (range
      62-527; p < 0.01) and 69 (range 45-207; p < 0.001), respectively. Hypercarbic ARF
      resolved within 6 h from admission even in the most severe cases. CONCLUSIONS:
      NPPV was a safe and effective first-line therapeutic approach in hypoxemic ARF
      children/infants with neuromuscular disease. It seems of importance to identify
      children with neuromuscular disorders who may be able to achieve residual
      ventilator-free breathing and to perform an NPPV trial avoiding tracheal
      intubation. Life-threatening respiratory distress and very young age should not
      preclude NPPV application in the PICU setting. The new helmet interface
      represents a promising tool for noninvasive ventilation in older children.

PMID- 16424642
TI  - The role of protein kinase C-alpha in hematologic malignancies.
AB  - In recent years advances in histopathological and molecular understanding of
      hematologic malignancies have led to the development of drugs which selectively
      target proteins associated with hematologic tumorigenesis. One such targeted
      agent is the antisense oligonucleotide aprinocarsen, which specifically inhibits
      the signaling protein, protein kinase C-alpha (PKC-alpha). Although PKC-alpha has
      been associated with tumorigenesis, its role and expression levels in patients
      with hematologic malignancies are not well understood. We here review studies
      investigating the expression and role of PKC-alpha in hematologic malignancies.
      Such a review may offer new insights on how to develop strategies in identifying
      patients that might best benefit from PKC-alpha inhibition.

PMID- 16424643
TI  - High-dose idarubicin, busulphan and melphalan for autologous stem cell
      transplantation in multiple myeloma responsive to DAV chemotherapy: comparison
      with a historical control.
AB  - Since 1997, 32 newly diagnosed multiple myeloma patients responsive to DAV
      chemotherapy were autografted with idarubicin-intensified busulphan-melphalan
      (ida-bu-mel). Main endpoints of the study were transplant-related toxicity,
      overall survival (OS) and progression-free survival (PFS). The results were
      compared with a historical control group of 38 patients treated with the
      'standard' bu-mel regimen. Concerning time to engraftment, no significant
      difference was observed between the two groups, while toxicity was significantly
      higher in the intensive conditioning group, regarding grade IV mucositis,
      duration of profound neutropenia, incidence of infections and platelet
      requirement. Five-year OS and PFS are 73 versus 78% and 37 versus 48% for the
      intensive and standard regimen, respectively (p value not significant). The ida
      bu-mel schedule appears to be a feasible and effective regimen for newly
      diagnosed multiple myeloma patients; nevertheless, no apparent benefit in OS and
      PFS arises from the comparison with a historical control treated with standard bu
      mel, which is better tolerated and at least equally effective.

PMID- 16424644
TI  - Frontline therapy with early intensification and autologous stem cell
      transplantation versus conventional chemotherapy in unselected high-risk,
      aggressive non-Hodgkin's lymphoma patients: a prospective randomized GEMOH
      report.
AB  - This prospective multicenter randomized trial compares conventional with early
      intensification with high-dose sequential chemotherapy (HDS) and autologous stem
      cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin
      lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate
      high (HI) and high-risk (HR)] NHL according to the international prognosis index
      (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week
      VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate
      was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression.
      According to intention-to-treat, with a median follow-up of 23 months, the 5-year
      actuarial overall survival, progression-free survival and disease-free survival
      in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p =
      nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated
      chemotherapy followed by intensification with HDS-ASCT does not seem to be
      superior to conventional chemotherapy in HI/HR aggressive NHL.

PMID- 16424645
TI  - Dose-dense CHOP plus rituximab (R-CHOP14) for the treatment of elderly patients
      with high-risk diffuse large B cell lymphoma: a pilot study.
AB  - BACKGROUND: Aggressive non-Hodgkin's lymphomas (NHL) require intensive therapies
      which seemed impracticable in elderly patients. Dose reduction and therapy
      attenuation reduced treatment-related toxicity, but also decreased therapeutic
      efficacy. In elderly patients too, the achievement of complete remission is the
      most important prognostic factor affecting outcome. Therefore, we have treated
      elderly patients with a dose-intensified protocol. Aim of the study was to verify
      the feasibility of this scheme in a subset of patients with high-risk aggressive
      lymphomas. METHODS: Between June 2002 and June 2004, 26 patients over the age of
      60 years with a diagnosis of aggressive NHL and an intermediate-high or high
      International Prognostic Index were treated with biweekly CHOP plus rituximab
      with the support of granulocyte colony-stimulating factors (G-CSF). RESULTS:
      Seventeen patients (65%) regularly kept the interval between cycles.
      Haematological and extrahaematological toxicities were moderate in all the
      patients. Twenty (77%) patients achieved complete remissions, 6 (23%) partial
      remissions with an overall response rate of 100%. After a median follow-up of 23
      months, the overall survival was 79%; after a median follow-up of 17 months, the
      disease-free survival was 70%. CONCLUSION: These results confirm that a dose
      dense CHOP programme can be administered safely and effectively in a subset of
      elderly patients with high-risk aggressive NHL. The addition of rituximab could
      increase the response rate without adding toxicity.

PMID- 16424646
TI  - Costs of chemotherapy for indolent follicular non-Hodgkin's lymphoma in the UK:
      an observational study.
AB  - Non-Hodgkin's lymphoma (NHL) is the sixth most common cancer in the United
      Kingdom (UK). This analysis assessed the health service costs of patients
      receiving chemotherapy for indolent follicular NHL based on a retrospective
      analysis of patient records in the UK. Each patient was followed up for a period
      of 3 years or until death. The analysis included 181 patients, who received a
      total of 187 treatment periods. Costs were estimated from the perspective of the
      UK National Health Service. The study found the cost of providing treatment with
      CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or fludarabine to
      patients with indolent follicular NHL to be lower than previously reported.

PMID- 16424647
TI  - Recombinant urate oxidase (rasburicase) for the prevention and treatment of tumor
      lysis syndrome in patients with hematologic malignancies.
AB  - In this multicenter, nonrandomized, open-label clinical trial conducted from July
      2003 to July 2004, recombinant urate oxidase (rasburicase) was administered to
      patients at risk for tumor lysis syndrome before or during the initiation of
      chemotherapy. Forty-five patients were enrolled, including 18 children (10 with
      acute lymphoblastic leukemia, 6 with high-grade lymphoma, and 2 with acute
      myeloid leukemia) and 27 adults (8 with acute lymphoblastic leukemia, 4 with high
      grade lymphoma, 9 with multiple myeloma, and 6 with acute myeloid leukemia). The
      age ranged from 3 to 98 years, with a median age of 7 years in children and 59.3
      years in adults. There were 14 males and 4 females in the pediatric group and 18
      males and 9 females in the adult group. Rasburicase 0.2 mg/kg was administered
      intravenously once a day for 2-6 days, for a median of 3 days in children and of
      4 days in adults. After 3 days of treatment, the median uric acid levels in the
      18 children decreased from 10.5 mg/dl (range 8-18.6) to 0.5 mg/dl (range 0.0
      1.7). Similarly, in the 27 adults, the median levels decreased from 10.8 mg/dl
      (range 8-24.4) to 0.5 mg/dl (range 0.0-1.6). No significant changes were observed
      in serum potassium, calcium, and phosphorus concentrations. None of the patients
      required dialysis for acute renal failure. Rasburicase was very well tolerated,
      with only 1 adult having grade 1 vomiting. We conclude that rasburicase is safe
      and highly effective for preventing the complications of tumor lysis syndrome in
      patients with hematologic malignancies.

PMID- 16424648
TI  - Splenectomy for chronic idiopathic thrombocytopenic purpura in children: a single
      center study in China.
AB  - The management of chronic and refractory idiopathic thrombocytopenic purpura
      (ITP) in children is controversial. We conducted a retrospective review of our
      single center experience in China between 1990 and 2003 with splenectomy for
      chronic ITP in children in order to determine the initial and long-term
      hematological response, morbidity, mortality, predictors of response to
      splenectomy and the therapy in children who failed splenectomy. Of 65 children
      analyzed, the overall immediate clinical response to splenectomy was 89.2%. The
      median postsplenectomy follow-up time was 52 months (8-124). During follow-up, 9
      children (13.8%) relapsed within a median time of 6 months (2-58). The overall
      morbidity was 1.5% and perioperative mortality was zero. During follow-up, 1
      child died of intracranial hemorrhage (ICH) and 1 died of overwhelming
      postsplenectomy infection (OPSI). The platelet count at day 7 after splenectomy
      was a predictor of a sustained response to splenectomy but no preoperative
      parameters were predictors of the response to splenectomy. Of the 15 children who
      failed splenectomy, excluding the one who died of ICH, only 2 children
      intermittently required corticosteroids and IVIG. Splenectomy is a potential
      therapy to provide long-term control of disease in children with chronic ITP and
      is associated with low morbidity and mortality. The risk of fulminant sepsis
      remains an omnipresent concern. Antipneumococcal vaccination and antibiotic
      prophylaxis should be recommended and children should receive timely and adequate
      antibiotics for bacteria infection to lessen the problem of OPSI.

PMID- 16424649
TI  - Randomized trial of anti-D immunoglobulin versus low-dose intravenous
      immunoglobulin in the treatment of childhood chronic idiopathic thrombocytopenic
      purpura.
AB  - BACKGROUND: Chronic idiopathic (immune) thrombocytopenic purpura (ITP) develops
      in approximately 20% of children with acute ITP. Six years ago, low-dose
      intravenous immunoglobulin (IVIG) treatment of childhood ITP was started at the
      Pediatric Hematology Unit, Ain Shams University, while intravenous anti-D has
      been introduced in Egypt in 2001. OBJECTIVES: To assess the efficacy and safety
      of intravenous anti-D compared to low-dose IVIG in the treatment of children with
      chronic ITP. PATIENTS AND METHODS: This randomized trial comprised 34 patients
      with chronic ITP (18 boys and 16 girls) with recurrent bleeding episodes. Median
      age of the patients was 6.5 years, duration of thrombocytopenia was > 6 months,
      and platelet count (PC) was < 30 x 10(9)/l (30 K). The patient cohort was divided
      into two subgroups: group A comprised 18 patients treated with anti-D in a dose
      of 50 microg/kg i.v. initially, and in 12 of them repeated doses (50 microg/kg)
      were given every 4 weeks, and group B consisted of 16 children who received IVIG
      in a dose of 250 mg/kg for 2 consecutive days. Bleeding manifestations, complete
      blood cell and reticulocyte counts were assessed at baseline and 3, 7, 14 and 28
      days after infusion. RESULTS: Clinically, more than 80% of the patients (82.3%)
      showed good control of bleeding. On day 3, 33.3% of group A versus 37.5% of group
      B, and on day 7: 66.6% of group A versus 75% of group B patients demonstrated a
      good response (PC > 50 K and/or doubling of baseline PC). On days 14 and 21, no
      significant changes in PCs were observed between both groups. However, only 11.1%
      of group A and 12.5% of group B patients could maintain PC > 100 K on day 28,
      while 38.8 versus 37.5% of group A and group B, respectively, still had PC > or =
      double the initial count. The peak response to anti-D was noticed 7 and 14 days
      following infusion and to IVIG on days 3 and 7. Repeated doses of anti-D could
      maintain PC > 50 K (or > double the baseline PC) in 75% of patients 1 week after
      infusion, and in 60% of them by day 28, with good control of bleeding.
      Splenectomy was postponed and/or avoided in 4 (33.3%) patients on anti-D
      maintenance therapy who experienced recurrent severe bleeding episodes before
      starting therapy. The safety of anti-D was judged by the degree of intravascular
      hemolysis. The mean hemoglobin decrease was 0.8 +/- 0.4 g/dl; in 61.1% of
      patients the Hb level dropped but none of them experienced a drop of more than 3
      g/dl or required transfusion. CONCLUSION: Both single intravenous anti-D and low
      dose IVIG effectively increased PC in children with chronic ITP at risk of
      bleeding or those with previous bleeding episodes. Repeated doses of anti-D could
      maintain PC above the critical values or double baseline counts in nearly two
      thirds of the patients showing good control of bleeding and may serve as an
      alternative to splenectomy in these patients.

PMID- 16424650
TI  - Side effects of oral iron prophylaxis in pregnancy--myth or reality?
AB  - BACKGROUND: It is a common belief among women that iron compounds have unpleasant
      gastrointestinal side effects. OBJECTIVE: To assess the gastrointestinal side
      effects of iron prophylaxis in pregnancy. METHODS: A randomized, double-blind
      study comprising 404 healthy pregnant women allocated to four groups taking
      ferrous iron supplement (as fumarate) in doses of 20 (n = 99), 40 (n = 100), 60
      (n = 102) and 80 mg (n = 103) daily from 18 weeks of gestation to delivery. Iron
      supplement was predominantly taken at bedtime. Gastrointestinal symptoms (nausea,
      vomiting, epigastric pain, eructation, pyrosis, meteorism, borborygmi, colic
      pain, flatulence, constipation, thin feces, diarrhea), black feces, and use of
      laxatives were recorded by interview at 18, 32 and 39 weeks of gestation.
      RESULTS: The frequencies of gastrointestinal symptoms were not significantly
      different in the four iron supplement groups either at inclusion or at 32 and 39
      weeks of gestation and thus not related to the iron dose. CONCLUSION: This study
      shows that a supplement of 20-80 mg ferrous iron (as fumarate), taken between
      meals, has no clinically significant gastrointestinal side effects. The
      implementation of iron prophylaxis to pregnant women should not be compromised by
      undue concern of non-existing side effects.

PMID- 16424651
TI  - Pregnancy and oral contraceptives in congenital bleeding disorders of the vitamin
      K-dependent coagulation factors.
AB  - Pregnancies and deliveries represent important hemostatic challenges for
      congenital coagulation disorders. The same is true for the assumption of oral
      contraceptives. Available information mainly deals with von Willebrand's disease,
      factor XI (FXI) deficiency and carriers of hemophilia A. Data concerning patients
      with congenital prothrombin complex factor deficiencies are very scanty. In the
      present study, data of a total of 27 women are presented, 11 patients with
      homozygous or double heterozygous deficiencies of FII, FVII and FX, together with
      16 cases of hemophilia B carriers. The patients with FII, FVII or FX defects had
      a total of 14 pregnancies and often needed transfusion therapy. Proper management
      resulted in a decrease in postpartum bleeding and satisfactory fetal outcome.
      Elective cesarean delivery seems indicated only in recent years. Carriers of
      hemophilia B had a total of 19 pregnancies but showed no bleeding and needed no
      substitutive therapy. Searching the literature, we discovered only 9 additional
      patients with prothrombin deficiency or FX deficiency, having a total of 16
      pregnancies. On the contrary, there were at least 17 additional patients with
      FVII deficiency, with a total of 21 pregnancies. The management of the diseases
      has been variable, but in substantial agreement with the personal observations.
      Oral contraceptive therapy was administered in some of our patients and in a few
      additional cases described in the literature. Medication was always well
      tolerated and patients who took it for a long period of time showed a decrease in
      menometrorrhagia and an improvement in hematocrit levels. This led to a decrease
      in transfusional needs and to improved general conditions.

PMID- 16424652
TI  - Von Willebrand factor 1 and factor 2 alleles (intron 40) are suitable markers for
      carrier detection in von Willebrand disease families in the Indian population.
AB  - The efficacy of the two von Willebrand factor (vWF) intron 40 variable number of
      tandem repeat (VNTR) markers, vWF1 and vWF2, in the genetic diagnosis of von
      Willebrand disease (vWD) in Indian patients was studied. Three hundred and sixty
      five unrelated normal individuals and 100 vWD patients (type 1: 18; type 2: 21;
      type 3: 61) were analyzed for the two vWF intron 40 VNTR markers. Polymerase
      chain reaction of the two markers vWF1 and vWF2 was done using specific primers
      followed by electrophoresis on 10% polyacrylamide gel. VNTR analysis revealed the
      presence of VNTR9 and VNTR15 along with the eight alleles VNTR6 to VNTR14 in the
      vWF1 marker. Furthermore, apart from the six alleles, VNTR1 to VNTR6 of the vWF2
      marker, two new alleles, VNTR7 and VNTR8, were also found. The heterozygosity
      rates were 75 and 74% for vWF1 and vWF2, respectively. Overall, the
      heterozygosity rate, i.e. when both vWF1 and vWF2 were considered in combination,
      was 81%. These data were successfully applied for the detection of carriers in 10
      severe type 3 vWD families. The high heterozygosity of the two vWF intron 40 VNTR
      markers and the simplicity of the technique without much cost being involved
      suggest the practical feasibility of this technique in developing countries like
      India.

PMID- 16424653
TI  - Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus.
AB  - Thrombotic thrombocytopenic purpura (TTP) occurring in patients with systemic
      lupus erythematosus (SLE) is rare and can be difficult to diagnose because of
      overlapping features of the two disorders. The aim of this study is to further
      characterize this uncommon association in terms of presenting features,
      diagnostic difficulties and treatment outcome. This is the largest series from a
      single centre with 6 patients diagnosed over a 6-year period. Two thirds of the
      patients had a simultaneous diagnosis of TTP and SLE. Half of the patients had a
      positive Coombs test along with clear features of TTP. Five patients received
      plasmapheresis as initial treatment while 1 patient received plasma infusions
      only. Four out of 5 patients responded to plasmapheresis and only 1 patient
      required cytotoxic therapy. TTP in association with SLE appears to be
      underdiagnosed and a positive Coombs test is not against the diagnosis of TTP in
      this setting. Most of the patients respond well to plasmapheresis. In case of a
      poor response, cytotoxic drugs should be considered early.

PMID- 16424654
TI  - Aberrant CD8 expression in B-chronic lymphocytic leukemia: report of five cases.
AB  - The expression of T cell-associated antigens on B cell non-Hodgkin lymphoma is
      rare. We describe 5 cases of B-chronic lymphocytic leukemia (B-CLL) with aberrant
      expression of CD8 on B cells. These B-CLL presented a typical immunophenotype
      CD19+, CD23+, FMC7- and CD5+ (except for 1 case) with a monotypic expression of
      surface immunoglobulin light chain kappa. The CD8 expression was confirmed on B
      CLL cells by two-color flow cytometry staining. We could not find coexpression of
      CD3 or CD4 on B-CLL cells. The clinical implications, the sensitivity to therapy
      and the prognostic outcome of this aberrant expression remains to be determined.

PMID- 16424656
TI  - Diastolic dysfunction and pulmonary hypertension in sickle cell anemia: is there
      a role for L-carnitine treatment?
AB  - Clinical manifestations of cardiovascular abnormalities in patients with sickle
      cell (SC) anemia are well documented. Many variables were assessed in our study
      before and after administration of L-carnitine to randomly selected 37 SC disease
      (SCD) children for a period of 6 months. Variables such as weight, height, serum
      ferritin levels, units of blood transfused and the number of veno-occlusive
      crises all showed significant improvement after the 6 months of therapy with L
      carnitine. Our study also showed that cardiac diastolic function and pulmonary
      hypertension are common in pediatric SCD patients. These two disorders showed
      some improvement after L-carnitine administration. Therefore, L-carnitine
      deserves a rigorous large-scale randomized clinical trial to evaluate its
      potential benefits as treatment for SCD patients with cardiac complications.

PMID- 16424655
TI  - Histone deacetylase inhibitor depsipeptide (FK228) induces apoptosis in leukemic
      cells by facilitating mitochondrial translocation of Bax, which is enhanced by
      the proteasome inhibitor bortezomib.
AB  - Histone deacetylase (HDAC) inhibitors are promising candidates for molecular
      targeted therapy for leukemia. In this study, we investigated the mechanisms of
      cytotoxic effects of depsipeptide (FK228), one of the most effective HDAC
      inhibitors against leukemia, using human myeloid leukemic cell lines HL-60 and
      K562. We found that FK228 activated caspase-9 and a subsequent caspase cascade by
      perturbing the mitochondrial membrane to release cytochrome c, which was almost
      completely blocked by overexpression of Bcl-2. The mitochondrial damage was
      caused by the translocation of Bax but not other pro-apoptotic Bcl-2 family
      proteins to the mitochondria. FK228 did not affect the interaction between Bax
      and Bax adaptor proteins such as 14-3-3theta and Ku70. FK228-induced apoptosis
      and mitochondrial translocation of Bax were markedly enhanced by the proteasome
      inhibitor bortezomib. The synergistic action of FK228 and bortezomib was at least
      partly mediated through conformational changes in Bax, which facilitate its
      translocation to the mitochondria. These results suggest that the combination of
      HDAC inhibitors and proteasome inhibitors is useful in the treatment of leukemia
      especially in the context of molecular-targeted therapy. The status of Bcl-2 and
      Bax may influence the sensitivity of tumors to this combination and thus can be a
      target of further therapeutic intervention.

PMID- 16424657
TI  - Trisomy 8 in prefibrotic early stages of chronic idiopathic myelofibrosis: a
      fluorescence in situ study of bone marrow biopsies.
AB  - Repeatedly performed bone marrow biopsies were studied in 30 patients with
      chronic idiopathic myelofibrosis (CIMF) by fluorescence in situ hybridization to
      detect and quantify trisomy 8 anomaly during the evolution of disease. For the
      establishment of threshold values we used negative and positive control
      specimens. At least 500 cells were evaluated in each specimen and only nuclei
      with three distinctive signals were regarded as positive. According to the
      controls, 27 patients revealed false-positive signals ranging from 0 to 1.2%
      (0.88 +/- 1.12). On the other hand, 3 patients showed an incidence of more than
      6.5% (up to 10.1%) in the initial prefibrotic as well as advanced fibro
      osteosclerotic stages of CIMF. In conclusion, trisomy 8 has been demonstrated
      already in the prodromal stages of CIMF and therefore is not limited to classical
      fibro-osteosclerotic manifestations.

PMID- 16424658
TI  - Hemochromatosis and severe iron overload associated with compound heterozygosity
      for TFR2 R455Q and two novel mutations TFR2 R396X and G792R.
AB  - We report three mutations of transferrin receptor 2 (TFR2)--R396X (exon 9; nt
      1186C-->T), R455Q (exon 10; nt 1364G-->A) and G792R (exon 18; nt 2374G-->A)--in a
      man of Scottish descent with hemochromatosis and severe iron overload. He was
      also heterozygous for the common HFE H63D polymorphism. The patient did not have
      coding region mutations in HAMP, FPN1, HJV or ALAS2. We conclude that this
      patient represents another example of hemochromatosis due to mutations of the
      gene encoding transferrin receptor 2.

PMID- 16424659
TI  - Development of thalassaemic iron overload cardiomyopathy despite low liver iron
      levels and meticulous compliance to desferrioxamine.
AB  - It is believed that myocardial iron deposition and the resultant cardiomyopathy
      only occur in the presence of severe liver iron overload. Using cardiovascular
      magnetic resonance, it is now possible to assess myocardial and liver iron levels
      as well as cardiac function in the same scan, allowing this supposition to be
      examined. We describe a patient with progressive myocardial iron deposition and
      the development of early iron overload cardiomyopathy despite excellent
      compliance to standard subcutaneous desferrioxamine, minimal liver iron and well
      controlled serum ferritin levels. These indirect markers remained far below the
      thresholds conventionally believed to be associated with increased cardiac risk.

PMID- 16424660
TI  - Continuous complete hematological and cytogenetic remission with molecular
      minimal residual disease 9 years after discontinuation of interferon-alpha in a
      patient with Philadelphia chromosome-positive chronic myeloid leukemia.
AB  - Interferon-alpha has been used as standard therapy for patients with Philadelphia
      positive chronic myeloid leukemia (CML) for more than 20 years. Recently
      randomized trials have shown a superiority of the tyrosine kinase inhibitor
      imatinib in respect to its efficacy to induce complete hematological and
      cytogenetic remissions and more importantly in overall survival. Although follow
      up is much shorter for imatinib than for interferon-alpha, this data changed the
      treatment algorithms in this disease. At the end of the era of interferon-alpha
      as a single-drug first-line treatment for most patients we present a case report
      which exemplifies a rare but exciting property of interferon-alpha in CML: the
      induction of complete hematological and cytogenetic remissions which can persist
      over years after discontinuation of the drug. Hence, the enrollment of CML
      patients in clinical trials which explore a combination treatment of imatinib and
      interferon-alpha is warranted.

PMID- 16424661
TI  - Chronic paraneoplastic cutaneous syndrome preceding an indolent variant of mantle
      cell lymphoma: favorable response to rituximab.
AB  - Mantle cell lymphoma (MCL) is an aggressive type of malignant lymphoma with short
      median survival despite conventional therapy. We describe the unusual case of a
      66-year-old man with a chronic skin rash which preceded the occurrence of an
      indolent MCL by 2 years. Repeated skin biopsies did not show involvement by the
      lymphoma. Short therapy with rituximab resulted in the complete and lasting
      resolution of the cutaneous lesions.

PMID- 16424662
TI  - Fulminant vasculitis: a rare fatal complication of lymphoma.
AB  - Vasculitis is rarely associated with lymphoma; however, most cases associated
      with lymphoma are cutaneous. Systemic vasculitis in association with lymphoma is
      usually an indolent and non-fatal complication. Two patients presented to our
      department with fulminant vasculitis with a fatal course and were later diagnosed
      with lymphoma. A search of the literature for systemic fulminant vasculitis in
      association with lymphoma disclosed eight case reports. We suggest that lymphoma
      should be considered as a possible etiology in patients with fulminant systemic
      vasculitis. The therapeutic implications of such an association are discussed.

PMID- 16424663
TI  - A juvenile hemochromatosis patient homozygous for a novel deletion of cDNA
      nucleotide 81 of hemojuvelin.
AB  - BACKGROUND: A 25-year-old woman of English/Irish background was diagnosed with
      hemochromatosis. She manifested hypogonadotrophic hypogonadism and congestive
      heart failure. Although there were abnormal liver function tests, no cirrhosis
      was present. The patient has been treated intermittently by phlebotomy for 24
      years. The aim of this study was to investigate the genetic basis of the
      patient's iron overload disease. METHODS: Genetic analysis was performed by
      direct sequencing of the genes for hemojuvelin, HFE, hepcidin, ferroportin and
      transferrin receptor 2. RESULTS AND CONCLUSIONS: Molecular analysis showed that
      the patient was homozygous for a previously undescribed mutation of HJV, the gene
      encoding hemojuvelin. This mutation, nt 81G deletion, causes a frameshift
      encoding 23 additional irrelevant amino acids and premature termination. No
      mutations were found in the other hemochromatosis genes, hepcidin, HFE,
      ferroportin or transferrin receptor 2, which might have contributed to her iron
      overload.

PMID- 16424664
TI  - Further characterization of anti-platelet monoclonal antibody HPL5 as anti
      glycoprotein V antibody.

PMID- 16424665
TI  - Platelet satellitism in lupus erythematosus resolving after treatment.

PMID- 16424666
TI  - Neuropsychological performance in mild cognitive impairment with and without
      apathy.
AB  - OBJECTIVE: To investigate the neuropsychological characteristics of patients
      diagnosed with mild cognitive impairment (MCI) with and without apathy. METHODS:
      A cohort of 245 MCI patients (mean age = 72 +/- 5.5 years; mean MMSE = 27.5 +/-
      1.3) was divided into two subgroups according to their Apathy Inventory score and
      underwent an extensive neuropsychological battery. RESULTS: There were 94 (38.4%)
      patients with and 151 (61.6%) patients without apathy. At baseline the apathetic
      subgroup had a significantly lower total score on the free and cued selective
      reminding test (FCSR). Furthermore, the apathetic subgroup showed a significant
      deterioration in FCSR total recall score between baseline and the 1-year
      assessment. In conclusion, the presence of apathy in MCI patients is not
      associated with frontal task performance but with a higher degree of memory
      impairment.

PMID- 16424667
TI  - Primary squamous cell carcinoma of the colon associated with hypercalcemia and
      hyperleukocytosis. Report of a case.
AB  - BACKGROUND/AIMS: Squamous cell carcinoma of the colon is a rare entity. We report
      a case of a patient who presented with a perforated squamous cell carcinoma of
      the sigmoid colon. RESULTS: A 45-year-old female presented with a 2-month history
      of worsening abdominal pain, bloody diarrhea, and vomiting. She underwent an
      exploratory laparotomy and was found to have keratinizing squamous cell carcinoma
      of the sigmoid colon that had perforated forming multiple abscess cavities. The
      postoperative course was complicated by hypercalcemia and persistent
      hyperleukocytosis, ultimately resulting in the patient's death. CONCLUSIONS: We
      present the second reported case of squamous cell carcinoma of the colon
      associated with hypercalcemia and the first reported case of associated
      hyperleukocytosis.

PMID- 16424669
TI  - Prevention of biliary leaks by biliary drainage after hydatid liver surgery.

PMID- 16424668
TI  - Non-occlusive small bowel necrosis during enteral feeding after
      pancreaticoduodenectomy.
AB  - BACKGROUND: Early enteral tube feeding is widely used after major surgery and
      trauma. This article is intended to alert surgeons to the possibility of small
      bowel necrosis following enteral refeeding and to discuss etiology and clinical
      features. METHODS: A case series from a single surgeon's database at a Tertiary
      Care Center is reported. Cases were drawnfrom a consecutive series of patients
      undergoing pylorus-preserving pancreaticoduodenectomy and placement of a needle
      catheter jejunostomy between January 1998 and June 2004. RESULTS: Two patients
      receiving early postoperative tube feeding developed sepsis with subsequent small
      bowel necrosis. Abdominal distension and signs of sepsis developed early
      postoperatively. Diagnosis was made based on characteristic computed tomography
      findings. Both patients underwent laparotomy with segmental bowel resection and
      survived. CONCLUSION: Non-specific septic symptoms associated with recurrent
      abdominal distension are ominous signs in patients receiving early postoperative
      enteral tube feeding and should prompt discontinuation of enteral nutrition.
      Within this scenario, CT imaging represents a valuable adjunct in the early
      assessment of these patients.

PMID- 16424670
TI  - Behcet's disease complicated with descending colon perforation.

PMID- 16424672
TI  - Multilocus linkage analysis of affected sib pairs.
AB  - OBJECTIVE: The conventional affected sib pair methods evaluate the linkage
      information at a locus by considering only marginal information. We describe a
      multilocus linkage method that uses both the marginal information and information
      derived from the possible interactions among several disease loci, thereby
      increasing the significance of loci with modest effects. METHODS: Our method is
      based on a statistic that quantifies the linkage information contained in a set
      of markers. By a marker selection-reduction process, we screen a set of
      polymorphisms and select a few that seem linked to disease. RESULTS: We test our
      approach on genome scan data for inflammatory bowel disease (InfBD) and on
      simulated data. On real data we detect 6 of the 8 known InfBD loci; on simulated
      data we obtain improvements in power of up to 40% compared to a conventional
      single-locus method. CONCLUSION: Our extensive simulations and the results on
      real data show that our method is in general more powerful than single-locus
      methods in detecting disease loci responsible for complex traits. A further
      advantage of our approach is that it can be extended to make use of both the
      linkage and the linkage disequilibrium between disease loci and nearby markers.

PMID- 16424671
TI  - Primary extranodal NK/T cell lymphoma ("nasal type") of the endometrium: report
      of an unusual case diagnosed at autopsy.
AB  - Primary natural killer (NK)/T cell lymphoma of the female genital tract is
      extremely rare. We here report the case of a "nasal type" NK/T cell lymphoma
      arising in the uterus. The diagnosis was established only at autopsy.

PMID- 16424674
TI  - Calcium and vitamin D metabolism in hypocalcemic vitamin D-resistant rickets
      carriers.
AB  - BACKGROUND/AIMS: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare
      monogenic autosomal recessive disorder associated with mutations in the gene of
      the vitamin D receptor (VDR), the mediator of 1,25(OH)2D3 action. Although many
      investigations have discussed the clinical manifestations and molecular etiology
      of this disease, only a few have investigated the biochemical and hormonal status
      of heterozygous HVDRR. The aim of the current work was to investigate the profile
      of selected biochemical and hormonal parameters related to the vitamin D
      endocrine system in a large number of HVDRR heterozygotes. METHODS: 67 relatives
      of 2 HVDRR patients, all members of an extended Greek kindred of five generations
      with a common ancestor, were included in the study. Direct sequencing was used to
      identify VDR gene mutations. Serum Ca, P, 25(OH)D, iPTH, and 1,25(OH)2D levels
      were determined in all members of the kindred. RESULTS: DNA analysis of the
      participants led to the design of two study groups: the HVDRR carriers (24) and
      the control subjects (43). Our results showed elevated circulating serum levels
      of 1,25(OH)2D3 and lower levels of PTH than their age- and sex-matched controls.
      No hypocalcemia or hypophosphatemia were detected in HVDRR carriers. CONCLUSIONS:
      Our findings suggest that HVDRR carriers may have compensatory elevated serum
      levels of 1,25(OH)2D3 through which they restrain PTH secretion. The study of
      HVDRR carriers could be a useful tool for the investigation of the vitamin D
      endocrine system.

PMID- 16424673
TI  - Autosomal-dominant isolated growth hormone deficiency (IGHD type II) with normal
      GH-1 gene.
AB  - BACKGROUND: Autosomal-dominant isolated GH deficiency (IGHD) is a rare disorder
      that is commonly believed to be due to heterozygous mutations in the GH-1 gene
      (GH-1). These mutations cause the production of a protein that affects the
      release of the product of the normal allele. Rarely, heterozygous mutations in
      the gene encoding for HESX-1 gene (HESX-1) may cause autosomal-dominant IGHD,
      with penetrance that has been shown to be variable in both humans and mice.
      SUBJECTS AND METHODS: We have sequenced the whole GH-1 in the index cases of 30
      families with autosomal-dominant IGHD. In all the families other possible causes
      of GH deficiency and other pituitary hormones deficits were excluded. We here
      describe the clinical, biochemical and radiological picture of the families
      without GH-1 mutations. In these families, we also sequenced the HESX-1. RESULTS:
      The index cases of the five families with autosomal-dominant IGHD had normal GH
      1, including the intronic sequences. They had no HESX-1 mutations. CONCLUSION:
      This study shows that GH-1 mutations are absent in 5/30 (16.6%) of the families
      with autosomal-dominant IGHD and raises the possibility that mutations in other
      gene(s) may be involved in IGHD with this mode of transmission.

PMID- 16424676
TI  - Insulin-like growth factor-1 increases intracellular calcium concentration in
      human primary neuroendocrine pancreatic tumor cells and a pancreatic
      neuroendocrine tumor cell line (BON-1) via R-type Ca2+ channels and regulates
      chromogranin a secretion in BON-1 cells.
AB  - Insulin-like growth factor 1 (IGF-1) is a potent mitogenic and secretory factor
      that acts on voltage operated Ca(2+) channels (VOCCs). VOCCs are categorized into
      L-type channels (Ca(V)1.1-1.4), P/Q-type channels (Ca(V)2.1), N-type channels
      (Ca(V)2.2), R-type channels (Ca(V)2.3), and T-type channels (Ca(V)3.1-3.3). Aside
      from regulating membrane excitability, VOCCs influence chromogranin A (CgA)
      secretion in neuroendocrine tumor (NET) cells. It is not known, whether VOCCs
      play a role in the IGF-1-dependent regulation of CgA secretion in NET cells. We
      therefore studied the effects of IGF-1 on individual VOCC subtypes and
      characterized their role in mediating IGF-1-dependent regulation of CgA secretion
      in NET cells. Using specific modulators of VOCC subtypes, we identified the
      functional expression of L-, N-, P/Q- and R-type channels in primary as well as
      permanent models of NET. The IGF-1-induced intracellular Ca(2+) increase in NET
      cells was mainly due to the activation of R-type channel activity. The effects on
      intracellular calcium, observed in whole-cell patch-clamp recordings and
      fluorescence imaging, were partially blocked by the specific R-type channel
      blocker SNX-482 and antisense oligonucleotides against the alpha(1) subunit of
      this channel. IGF-1 potently induced CgA secretion. The effect of IGF-1 was
      reduced by both, inhibition of R-type channel activity and a reduction of R-type
      channel expression using antisense oligonucleotides. Since R-type channels exist
      in NET cells and couple to both, IGF-1 receptor signaling as well as CgA
      secretion, pharmacological interference with R-type channels may represent a new
      therapeutic option by blocking Ca(2+) signaling thereby abrogating IGF-1
      dependent hypersecretion in NET disease.

PMID- 16424675
TI  - The Mayo Clinic cohort study of personality and aging: design and sampling,
      reliability and validity of instruments, and baseline description.
AB  - We established a historical cohort of 7,216 subjects who completed the Minnesota
      Multiphasic Personality Inventory (MMPI) at the Mayo Clinic from 1962 through
      1965 for research (not clinical indication), and who resided within a 120-mile
      radius centered in Rochester, Minnesota. We describe here the overall cohort
      design and sampling, we report results concerning reliability and validity, and
      we describe age and sex patterns at baseline for four MMPI scores of primary
      interest (depression, anxiety, social introversion, and negativity). Subjects
      excluded from the cohort because of missing data had MMPI scores similar to
      subjects included (after appropriate rescaling). A cut-off specific for age and
      sex at the 75th percentile of the distribution of raw scores was valid compared
      with the traditional clinical cut-off (T scores plus one standard deviation).
      Baseline scores for all four scales were higher in women than in men at all ages
      (all p < 0.0001). Depression and social introversion scores showed an increasing
      trend with age in both sexes (Spearman rank correlation, rho = 0.05 and 0.08,
      respectively, p < 0.0001 for both). Baseline scores on the anxiety scale showed a
      decreasing trend with age in both sexes (rho = -0.06, p < 0.0001). Negativity
      scores remained relatively stable with age in both sexes (rho = 0.03, p = 0.01).
      We found a high correlation between the anxiety score and the negativity score
      (rho = 0.90, p < 0.0001) even after the exclusion of overlapping items (rho =
      0.68, p < 0.0001). This newly established historical cohort study provides
      opportunities to test hypotheses regarding the link between personality and
      aging, aging-related diseases, and overall mortality.

PMID- 16424677
TI  - Trade-off between L-thyroxin and melatonin in immune regulation of the Indian
      palm squirrel, Funambulus pennanti during the reproductively inactive phase.
AB  - The thyroid gland and its hormones have been reported to influence reproduction
      and metabolism in a positive manner. However, research to date provides strong
      evidence for a reciprocal relationship between the immune system and hormones of
      the hypothalamus-pituitary-thyroid axis. The present study has been taken to
      elucidate the effect of L-thyroxin (T(4)) on immune parameters such as total
      leukocyte count, percent lymphocyte count, blastogenic response and percent
      stimulation ratio of thymocytes and splenocytes of a seasonally breeding rodent,
      Funambulus pennanti, during its reproductively inactive phase when peripheral
      T(4) is low. Treatment with L-thyroxin at a near-physiological dose of 35
      microg/100 g body weight during evening hours showed a significant elevation of
      all immune parameters. However, combined treatment of L-thyroxin and melatonin
      (25 microg/100 g body weight) had no additive effect. On the other hand, in vitro
      supplementation of T(4) (10(-6) M) either alone or in combination with melatonin
      (0.5 microM) did not induce any significant change on thymocyte and splenocyte
      proliferation. Therefore, a trade-off effect of L-thyroxin and melatonin on the
      immune system (T- and B-cell differentiation) is suggested for this rodent.

PMID- 16424678
TI  - Power frequency magnetic fields increase cell proliferation in the mammary gland
      of female Fischer 344 rats but not various other rat strains or substrains.
AB  - Epidemiological data have raised concerns about the relationship between exposure
      to power frequency magnetic fields (MFs) and breast cancer. We have shown
      previously that 50-Hz MFs at microtesla flux densities enhance mammary gland
      tumor development and growth in the 7,12-dimethylbenz[a]anthracene (DMBA) model
      of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF
      exposure results in an enhanced proliferative activity of the mammary epithelium
      of SD rats, which is a likely explanation for the cocarcinogenic or tumor
      promoting effects of MF exposure in the DMBA model. Comparison of different SD
      substrains indicated that the genetic background plays a pivotal role in these
      effects of MF exposure. This prompted us to compare the effects of MF exposure
      (100 microT, 2 weeks) on cell proliferation in the mammary gland in eight
      different strains and substrains of outbred and inbred rats. Proliferation of
      epithelial cells in the mammary tissue and adjacent skin was examined by labeling
      proliferating cells with bromodeoxyuridine (BrdU). In addition to the MF
      sensitive SD substrain (SD1) previously used in our experiments, Fischer 344 rats
      were the only strain in which MF exposure significantly enhanced BrdU labeling in
      the mammary epithelium, indicating a marked increase in cell proliferation. The
      MF-induced increase in BrdU labeling in Fischer 344 rats was similar to that seen
      after DMBA application. Furthermore, whole mount analysis of mammary tissue from
      Fischer 344 rats demonstrated that MF exposure increased the number of terminal
      end buds, i.e. the site of origin of mammary carcinomas. By comparison with MF
      insensitive inbred rat strains, Fischer 344 rats may serve to evaluate the
      genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting
      effects of MF exposure.

PMID- 16424680
TI  - Potent bystander effect in suicide gene therapy using neural stem cells
      transduced with herpes simplex virus thymidine kinase gene.
AB  - OBJECTIVE: The herpes simplex virus thymidine kinase (HSVtk)/ganciclovir suicide
      gene therapy system has been considered as one of the most promising therapeutic
      strategies for malignant gliomas. We have been using HSVtk gene-transduced neural
      stem cells (NSCtk) that possess an ability to migrate toward a tumor mass for the
      treatment of experimental brain tumors. In the present study, we evaluated the
      potency of anti-tumor effect mediated by the bystander effect between NSCtk and
      C6 glioma cells in the HSVtk/ganciclovir suicide gene therapy system. METHODS:
      NSCtk and C6 glioma cells were mixed at various ratios (NSCtk:C6 cell ratios of
      1:1 to 1:64) and the bystander effect was evaluated both under in vitro and in
      vivo conditions. RESULTS: In vitro co-culture experiment showed a complete tumor
      growth inhibition at the NSCtk:C6 ratios as low as 1:16. In vivo co-implantation
      study in the rat brain showed no visible tumors at the NSCtk:C6 ratios as low as
      1:16 and all those rats survived more than 100 days. CONCLUSION: The results
      clearly demonstrated an extremely potent bystander effect between NSCtk and C6
      cells, and the minimum number of NSCtk cells needed for the treatment of tumors
      was roughly estimated.

PMID- 16424679
TI  - Rituximab, Ara-C, dexamethasone and oxaliplatin is safe and active in heavily
      pretreated patients with diffuse large B-cell lymphoma.
AB  - OBJECTIVE: Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who are
      either not suitable for stem cell transplantation or suffer from relapsed disease
      after standard second-line chemotherapy face a dismal prognosis. Most of them
      have a reduced performance status and do not tolerate intensive chemotherapy.
      METHODS: Twenty patients with relapsed DLBCL were given rituximab 375 mg/m(2)
      intravenously on day 1, Ara-C 2 x 1,000 mg intravenously on day 2, dexamethasone
      40 mg intravenously on days 1-4, and oxaliplatin 130 mg/m(2) intravenously over 2
      h on day 3 (R-ADOx). RESULTS: Five patients (25%) achieved a complete remission,
      9 (45%) had a partial response , 2 (10%) had stable disease with improvement in
      performance status, while 4 patients (20%) progressed. The median survival was 11
      months (range 1-13). Despite extensive pretreatment, side effects were relatively
      mild and consisted of thrombocytopenia WHO grade III in 9 (45%) and grade IV in 2
      (11%) patients, leukocytopenia WHO grade III in 10 (50%) cases (with infectious
      episodes in 2 patients), and transient peripheral neuropathy in 9 (45%) patients.
      CONCLUSION: R-ADOx is well tolerated in heavily pretreated patients with an
      impaired performance status. In addition, it displays impressive therapeutic
      activity given the highly unfavorable patient characteristics and should be
      further investigated for treatment of DLBCL.

PMID- 16424681
TI  - Shared obsessive-compulsive disorder.
AB  - BACKGROUND: Shared psychotic disorder (folie a deux) is an uncommon entity
      reported mainly in the context of delusions. Obsessions and compulsions occur
      very rarely as shared psychopathology. MATERIAL AND METHODS: We present two
      sisters who manifested shared obsessive-compulsive disorder. RESULTS: Both
      sisters were managed in keeping with their shared obsessive-compulsive disorder
      leading onto a similar pattern of response. CONCLUSIONS: Shared obsessions could
      represent the continuum concept of obsessions and delusions, and their
      relationship needs to be evaluated in greater detail.

PMID- 16424682
TI  - Inverse correlation between severity of psychopathic traits and serum cortisol
      levels in young adult violent male offenders.

PMID- 16424683
TI  - A probabilistic functional atlas of the VIM nucleus constructed from pre-, intra-
      and postoperative electrophysiological and neuroimaging data acquired during the
      surgical treatment of Parkinson's disease patients.
AB  - We have previously introduced a concept of a probabilistic functional atlas (PFA)
      to overcome limitations of the current electronic stereotactic brain atlases:
      anatomical nature, spatial sparseness, inconsistency and lack of population
      information. The PFA for the STN has already been developed. This work addresses
      construction of the PFA for the ventrointermediate nucleus (PFA-VIM). The PFA-VIM
      is constructed from pre-, intra- and postoperative electrophysiological and
      neuroimaging data acquired during the surgical treatment of Parkinson's disease
      patients. The data contain the positions of the chronically implanted electrodes
      and their best contacts. For each patient, the intercommissural distance, height
      of the thalamus and width of the third ventricle were measured. An algorithm was
      developed to convert these data into the PFA-VIM, and to present them on axial,
      coronal and sagittal planes and in 3-D. The PFA-VIM gives a spatial distribution
      of the best contacts, and its probability is proportional to best contact
      concentration in a given location. The region with the highest probability
      corresponds to the best target. The PFA-VIM is calculated with 0.25-mm3
      resolution from 107 best contacts in two situations: with and without lateral
      compensation against the width of the third ventricle. For the PFA-VIM
      compensated laterally, the anterior, lateral and dorsal coordinates of the mean
      value are (in mm) 6.24, 13.83, 1.68 for the left VIM and 6.54, -13.84, 2.10 for
      the right VIM. The coordinates of the mean value of the highest probability
      region along with the highest number of the best contacts (P) are: 6.25, 14.25,
      1.75, P = 16, for the left VIM, and 6.0, -14.0, 1.00, P = 18, for the right VIM.
      The coordinate system origin is at the posterior commissure. For the PFA-VIM not
      compensated laterally, the coordinates of the mean value are 6.24, 13.99, 1.68
      for the left VIM and 6.53, -14.13, 2.10 for the right VIM. The coordinates of the
      mean value of the highest probability region along with the highest number of the
      best contacts are 5.58, 13.67, 1.33, P = 14, for the left VIM, and 6.36, -14.03,
      1.11, P = 17, for the right VIM. The PFA-VIM atlas overcomes several limitations
      of the current anatomical atlases and can improve targeting of thalamotomies and
      thalamic stimulations. It is dynamic and can easily be extended with new cases.

PMID- 16424684
TI  - Multimodality treatment of trigeminal neuralgia.
AB  - Most trigeminal neuralgia (TN) studies focus on a single strategy, microvascular
      decompression (MVD) or percutaneous rhizotomy (PR). We use a multimodality
      approach to TN. We perform MVD on patients younger than 70 years and PR on older
      patients or those where MVD has failed. We performed a chart review of the
      procedures for TN over the past 3 years and used a questionnaire for long-term
      follow-up. The questionnaire asked patients to rate their pre- and postoperative
      pain, outcome, and medication changes. Seventy-four procedures (40 MVDs and 34
      PRs) were performed on 67 patients. Twenty patients had undergone previous
      procedures. 93% of the patients had significant initial pain relief. Over a 1.2
      year mean follow-up, 51% of the patients had complete pain relief while 27% had a
      substantial improvement. There were no deaths and 5 complications. Our results
      suggest that a multimodality approach to TN yields excellent results with minimal
      complications.

PMID- 16424685
TI  - Stereotactic radiosurgery as a salvage treatment for recurrent skull base adenoid
      cystic carcinoma.
AB  - Twelve patients (15 lesions) with recurrent skull base adenoid cystic carcinoma
      (ACC) were treated by Gamma Knife stereotactic radiosurgery (SRS). The tumor
      volume ranged from 2 to 103 ml (median 15 ml). Treatment was prescribed at the 40
      60% isodose line and ranged from 10 to 18 Gy (median: 13.0 Gy). The median follow
      up period was 18 months (range 3-55). Six patients were alive and 6 dead at the
      end of the follow-up period. Only 1 patient died from local tumor recurrence. Ten
      among 15 tumors treated by SRS decreased in size until the end of the follow-up
      period or the patients' death. Three remained unchanged in size. Two tumors
      initially regressed but then increased in size. In selected patients with
      recurrent skull base ACC, SRS can be considered as a salvage treatment with good
      local control.

PMID- 16424686
TI  - Age-related normal variants of sternal uptake on bone scintigraphy.
AB  - PURPOSE: The purpose of this study was to describe the variable age-related
      normal appearance of the sternal area on bone scintigraphy. METHODS: We studied
      334 patients (158 males and 176 females) aged 15 days to 85 years, mean age 32.5
      +/- 19.9 years, who did not have symptoms associated with the sternum and chest
      wall or a history of malignancy. All patients underwent whole-body bone scan 3
      hours after intravenous injection of Tc-99m MDP. RESULTS: In patients younger
      than 10 years, sternal uptake was equal to nearby ribs with homogeneous uptake
      and poorly defined outlines. In older patients, the sternum showed markedly
      greater uptake than nearby ribs and the borders became well defined. Different
      patterns of sternal uptake were noted: 1) increased uptake in the manubrium; 2)
      hot spots in the angle of Louis, body and xiphoid; 3) a photopenic area just
      above the xiphoid process; 4) heterogeneous sternal body uptake; and 5)
      hyperactivity along the sternal body borders. Of these variants, the angle of
      Louis hot spot was the most common finding (63.5%). A linear pattern of hot spots
      in the sternal body was seen most frequently between 10 and 30 years old and
      corresponded to 3 transverse ridges of bone, representing the sites of union.
      Increased tracer uptake only at the medial end of the clavicle in the SC joints
      was seen in 42.13% of patients younger than 30 years. CONCLUSION: This study
      showed age-related normal variants of sternal uptake on bone scanning in
      asymptomatic patients. Understanding these variants may be helpful in
      differentiating normal and abnormal patterns of uptake in the sternum on
      radionuclide bone imaging.

PMID- 16424687
TI  - Intracardiac extension of lung cancer demonstrated on PET scanning.
AB  - Intracardiac tumors are unusual and can originate within the heart or spread from
      other sites. This is a report of a patient who presented with a TIA, and during
      the subsequent stroke workup, a right hilar nonsmall cell lung carcinoma was
      discovered. The tumor had extended into the left atrium through a pulmonary vein.
      The hilar tumor as well as intracardiac extension were demonstrated by PET
      scanning using FDG.

PMID- 16424688
TI  - Paradoxic technetium-99 methylene diphosphonate localization in malignant
      mesothelioma.
AB  - The literature is replete with cases of Tc-99m bone imaging agent uptake in
      pleural effusions. Far rarer is the report of photopenia in a pleural effusion.
      In this case of malignant mesothelioma, we describe a unique case of unilateral
      hemithoracic photopenia from a pleural effusion with concomitant uptake in the
      contralateral lung resulting from calcified pleural plaques. Although initially
      perplexing clinically, this case can be readily explained with an understanding
      of basic physiological principles.

PMID- 16424689
TI  - Incidental parathyroid adenoma mimicking tumor recurrence in a patient with
      follicular thyroid carcinoma.
AB  - We report the case of a 59-year-old woman with a history of follicular thyroid
      cancer who had reoperation for suspected local tumor recurrence as laboratory
      (tumor marker), imaging findings (ultrasound, I-131 scintigraphy and Tc-99m-MIBI
      scintigraphy), and also fine needle aspiration (FNA) cytology were equivocal.
      However, postoperative histopathology revealed a parathyroid adenoma.

PMID- 16424690
TI  - Reversible rib photopenia demonstrated by bone scan in vaso-occlusive
      complication of systemic lupus erythematosus.

PMID- 16424691
TI  - Thoracic cage uptake in bone scintigraphy secondary to lung abscess with
      extrapleural invasion.

PMID- 16424692
TI  - Functional and morphologic imaging of bilateral chronic avascular necrosis of the
      talus.

PMID- 16424693
TI  - Imaging in acute pyogenic spondylitis.

PMID- 16424694
TI  - Avulsive cortical irregularity and F-18 FDG PET.

PMID- 16424695
TI  - Tc-99m MDP bone and Ga-67 citrate scintigraphy of Erdheim-Chester disease in a
      child.

PMID- 16424696
TI  - Value of hepatobiliary scintigraphy after type 1 choledochal cyst excision and
      Roux-en-Y hepatojejunostomy.

PMID- 16424697
TI  - Myocardial perfusion SPECT defects resulting from cystic echinococcosis in the
      pericardium.

PMID- 16424698
TI  - Superior vena cava obstruction as suggested by extrapulmonary uptake on lung
      scintigraphy.

PMID- 16424699
TI  - Bronchopulmonary carcinoid tumor and related cervical vertebral metastasis with
      PET-positive and octreotide-negative scintigraphy.

PMID- 16424700
TI  - Herpes Zoster mimicking recurrence of lymphoma on PET/CT.

PMID- 16424701
TI  - Metastatic inflammatory myofibroblastic tumor imaged by PET/CT.

PMID- 16424703
TI  - Current readings in nuclear medicine.

PMID- 16424702
TI  - Occult carcinoma of the thyroid presenting with orbital metastasis.

PMID- 16424704
TI  - High-dose antithrombin III in the treatment of severe sepsis in patients with a
      high risk of death: efficacy and safety.
AB  - OBJECTIVE: To explore if patients with severe sepsis and with a predicted high
      risk of death (according to the Simplified Acute Physiology Score II) might have
      a treatment benefit from high-dose antithrombin III. DESIGN: Subgroup analysis of
      a randomized, placebo-controlled, double-blind, prospective phase III study.
      SETTING: Unifactorial and multifactorial reanalysis of prospectively defined
      populations from the KyberSept trial. PATIENTS: We studied 1,008 patients (43.6%
      of the overall intention-to-treat population, n = 2,314) with a predicted
      mortality rate of 30-60% at study entry as defined by the Simplified Acute
      Physiology Score II. INTERVENTIONS: Patients were randomized in a 1:1 fashion to
      receive either high-dose antithrombin III (30,000 IU intravenously over the
      period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS: In a Kaplan-Meier
      analysis of patients with a predicted mortality of 30-60%, the survival time when
      followed up for 90 days after admission was increased in the high-dose
      antithrombin III group compared with placebo (p = .04). If heparin was avoided
      during the 4-day treatment phase with high-dose antithrombin III (n = 140) or
      placebo (n = 162), the treatment effect appeared to be even more pronounced: 28
      day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval,
      0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95%
      confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk
      ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall
      population, the percentage with any bleeding was increased in patients receiving
      high-dose antithrombin III compared with placebo. Survival rates were in favor of
      high-dose antithrombin III in patients both with and without bleeding
      complications. CONCLUSIONS: Treatment with high-dose antithrombin III may
      increase survival time up to 90 days in patients with severe sepsis and high risk
      of death. This benefit may even be stronger when concomitant heparin is avoided.

PMID- 16424705
TI  - Serum vasopressin concentrations in critically ill patients.
AB  - OBJECTIVE: To measure arginine vasopressin (AVP) serum concentrations in
      critically ill patients. DESIGN: Prospective study. SETTING: Twelve-bed general
      and surgical intensive care unit in a tertiary, university teaching hospital.
      PATIENTS: Two-hundred-thirty-nine mixed critically ill patients and 70 healthy
      volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data,
      hemodynamic variables, vasopressor drug requirements, blood gases, AVP serum
      concentrations within 24 hrs after admission, multiple organ dysfunction score,
      and outcome were recorded. Twenty-four hours after admission, study patients had
      significantly higher AVP concentrations (11.9 +/- 20.6 pg/mL) than healthy
      controls (0.92 +/- 0.38 pg/mL; p < .001). Males had lower AVP concentrations than
      females (9.7 +/- 19.5 vs. 15.1 +/- 20.6 pg/mL; p = .014). Patients with
      hemodynamic dysfunction had higher AVP concentrations than patients without
      hemodynamic dysfunction (14.1 +/- 27.1 vs. 8.7 +/- 10.8 pg/mL; p = .042).
      Patients after cardiac surgery (n = 96) had significantly higher AVP
      concentrations when compared to patients admitted for other diagnoses (n = 143; p
      < .001). AVP concentrations were inversely correlated with length of stay in the
      intensive care unit (correlation coefficient, -0.222; p = .002). There was no
      correlation between serum AVP concentrations and the incidence of shock or
      specific hemodynamic parameters. Four (1.7%) of the 239 study patients met
      criteria for an absolute AVP deficiency (AVP, <0.83 pg/mL), and 32 (13.4%) met
      criteria for a relative AVP deficiency (AVP, <10 pg/mL, and mean arterial
      pressure, <70 mm Hg). In shock patients, relative AVP deficiency occurred in
      22.2% (septic shock), 15.4% (postcardiotomy shock), and 10% (shock due to a
      severe systemic inflammatory response syndrome) (p = .316). CONCLUSIONS: AVP
      serum concentrations 24 hrs after intensive care unit admission were
      significantly increased in this mixed critically ill patient population. The lack
      of a correlation between AVP serum concentrations and hemodynamic parameters
      suggests complex dysfunction of the vasopressinergic system in critical illness.
      Relative and absolute AVP deficiency may be infrequent entities during acute
      surgical critical illness, mostly remaining without significant effects on
      cardiovascular function.

PMID- 16424706
TI  - Underuse of lung protective ventilation: analysis of potential factors to explain
      physician behavior.
AB  - OBJECTIVE: To determine the frequency of use of low-tidal-volume ventilation in
      appropriate patients with acute lung injury (ALI) and the factors associated with
      the choice of tidal volume. DESIGN: Prospective observational cohort study of
      patients identified with ALI or acute respiratory distress syndrome from
      September 2000 to November 2002. SETTING: Medical and surgical intensive care
      unit (ICU) at an academic tertiary-care hospital. MEASUREMENTS AND MAIN RESULTS:
      Measurements included the proportion for whom the ventilation tidal volume (TV)
      was <or=7.5 mL/kg predicted body weight (PBW) on days 2, 4, and 7 of ALI and the
      proportion for whom the ventilation TV was <or=6.5 and <or=8.5 mL/kg/PBW
      (sensitivity analysis). Demographic and clinical characteristics of patients
      undergoing ventilation with low and high TV were compared. Of 88 total patients
      studied, 39% had ventilation with TV <or=7.5 mL/kg/PBW on day 2 of ALI, 49% on
      day 4, and 56% on day 7. In contrast, 49% of patients had ventilation with TV
      >8.5 mL/kg/PBW on day 2 of ALI, 30% on day 4, and 24% on day 7. The use of low TV
      was significantly associated with clinical parameters indicative of worse disease
      severity, including low values for Pao2 (p = .01), Pao2/Fio2 (p = .08), and
      static compliance of the respiratory system (p = .006). CONCLUSIONS: Ventilation
      with a low TV was used in a minority of patients with ALI, despite results
      published in 1998 and 2000 supporting this approach. This may be related to
      clinicians' underrecognition of less severe cases of ALI, their reserving of low
      TV ventilation for more severe cases, or both.

PMID- 16424707
TI  - Role of inducible nitric oxide synthase in the reduced responsiveness of the
      myocardium to catecholamines in a hyperdynamic, murine model of septic shock.
AB  - OBJECTIVES: Excess nitric oxide production is a key mediator of hypotension and
      catecholamine-resistance in septic shock. Although nitric oxide synthase blockade
      has been shown to restore hemodynamics, conflicting results on myocardial
      function were reported. Inducible nitric oxide synthase (iNOS) knockout (iNOS-/-)
      mice showed improved heart function, but these results were obtained during
      hypodynamic shock characterized by reduced cardiac output. Therefore, we
      investigated heart function and catecholamine responsiveness in a clinically
      relevant, murine model of cecal ligation and puncture (CLP)-induced septic shock.
      DESIGN: Prospective, controlled, randomized animal study. SETTING: University
      animal research laboratory. SUBJECTS: Male C57Bl/6 wild-type and iNOS-/- mice.
      INTERVENTIONS: Fifteen hours after CLP, three groups of mice (wild-type controls,
      n = 9; iNOS-/-, n = 12; and wild-type mice receiving 5 mg x kg(-1)
      intraperitoneally of the selective iNOS inhibitor GW274150 immediately after CLP,
      n = 8) were anesthetized, mechanically ventilated, and instrumented (central
      venous and left ventricular pressure-conductance catheter). Measurements were
      recorded 18, 21, and 24 hrs post-CLP. Hydroxyethylstarch and norepinephrine were
      infused to achieve normotensive and hyperdynamic hemodynamics. MEASUREMENTS AND
      MAIN RESULTS: There was no intergroup difference in mean arterial pressure,
      stroke volume, and left ventricular ejection fraction. Norepinephrine doses
      required to achieve the hemodynamic targets were lower in GW274150 (p < .001 vs.
      controls) and even further reduced in iNOS-/- mice (p < .001 vs. controls, p <
      .001 vs. GW274150). In the control group, the higher norepinephrine doses
      resulted in significantly higher heart rates and consequently cardiac output,
      maximal contraction, and relaxation than in the GW274150 and iNOS-/- animals.
      Left ventricular end-diastolic volume was also significantly higher in the
      controls than in the GW274150 and iNOS-/- mice, whereas left ventricular end
      diastolic pressure did not differ. CONCLUSIONS: Our results confirm septic shock
      related impaired left ventricular function. Genetic iNOS deletion and
      pharmacologic iNOS blockade enhanced cardiac norepinephrine responsiveness due to
      improved systolic function. In contrast, iNOS inhibition seemed to be affiliated
      with compromised left ventricular relaxation.

PMID- 16424708
TI  - New disseminated intravascular coagulation score: A useful tool to predict
      mortality in comparison with Acute Physiology and Chronic Health Evaluation II
      and Logistic Organ Dysfunction scores.
AB  - OBJECTIVE: To compare the performance of a coagulation score-the new scoring
      system for diagnosing disseminated intravascular coagulation (DIC)-with the Acute
      Physiology and Chronic Health Evaluation (APACHE) II and Logistic Organ
      Dysfunction score in mortality prediction. DESIGN: Single-center retrospective
      study. SETTING: Medical intensive care unit of the University of Munich.
      PATIENTS: A total of 797 patients admitted to the intensive care unit between
      January 1, 1996, and January 1, 2001. METHODS: A retrospective analysis of all
      patients was done if the coagulation variables d-dimer, platelet count,
      fibrinogen, and prothrombin index were available within the first 12 hrs after
      admission. Patients with missing values, fibrinolytic therapy, or unknown
      survival status were excluded from analysis. As a marker of fibrin generation, d
      dimer was measured and integrated into the scoring system for DIC together with
      prothrombin time, fibrinogen, and platelet count. A coagulation score was
      calculated in analogy with the scoring system for DIC in patients not typically
      developing DIC. MEASUREMENTS AND RESULTS: Overall, the mean result of the scoring
      system for DIC was 2.2 points. An increasing scoring system for DIC was
      associated with increasing mortality in patients with serious infections. Use of
      the scoring system for DIC in addition to the APACHE II score helps to predict
      mortality better than the APACHE II score alone, especially in patients with
      infections. The Cox regression analysis showed that the DIC and APACHE II scores
      correlated independently with survival time with a greater effect of the DIC
      score than the APACHE II or the Logistic Organ Dysfunction score. Similar results
      were obtained using the coagulation score in patients with cardiocirculatory
      diseases. CONCLUSION: Our retrospective data suggest that a combination of the
      APACHE II score and the scoring system for DIC predicts mortality in critically
      ill patients with available variables better than the APACHE II score alone. This
      effect is most pronounced among patients with active infection. These results of
      our retrospective analysis have to be confirmed in a prospective study.

PMID- 16424709
TI  - Ventilatory and hemodynamic management of potential organ donors: an
      observational survey.
AB  - OBJECTIVE: To determine the current standard ventilatory and cardiovascular
      management in potential organ donors. DESIGN: Prospective, multiple-center,
      observational survey. SETTING: A total of 15 intensive care units in 13 hospitals
      in Piedmont, Italy. PATIENTS: A total of 34 brain-dead patients enrolled in 6
      months. MEASUREMENTS AND MAIN RESULTS: Demographics and reasons for lung
      transplant exclusion were recorded. Ventilatory and hemodynamic variables were
      compared before and after confirmation of brain death. A total of 23 potential
      donors were ineligible for lung donation based on pulmonary status and age. Of
      the 11 eligible lung donors, only two donated the lungs because five had
      Pao2/Fio2 ratios of <300 and four were ineligible for logistic problems. Tidal
      volume was 10 +/- 2 mL/kg, positive end-expiratory pressure was 3.3 +/- 2.7 cm
      H2O, Fio2 was 50% +/- 18% before brain death diagnosis, and no changes were made
      after brain death confirmation. In potential lung donors, apnea tests were
      performed with apneic oxygenation after disconnection from the ventilator in all
      cases; tracheal suction was performed with an open circuit in eight cases, and no
      recruitment maneuvers were performed. Crystalloid infusion was increased after
      diagnosis of brain death from 187 +/- 151 to 275 +/- 158 mL/hr (p < .05), and
      central venous pressure increased from 6 +/- 3 to 7 +/- 3 mm Hg (p < .05).
      Inotropic support was used in 24 donors (70%). CONCLUSIONS: Five of 11 potential
      lung donors (45%) had a Pao2/Fio2 ratio of <300, making them ineligible for lung
      donation. After the diagnosis of brain death, ventilatory management remained the
      same, no maneuvers for prevention of derecruitment of the lung were performed,
      and cardiovascular management was modified to optimize peripheral organ
      perfusion. These data represent the current standard of care for ventilatory
      management of potential organ donors and may be suboptimal in preserving lung
      function.

PMID- 16424711
TI  - Comparison of antimicrobial cycling and mixing strategies in two medical
      intensive care units.
AB  - OBJECTIVE: To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas
      antibiotics on the acquisition of resistant Gram-negative bacilli in the critical
      care setting. DESIGN: Prospective, open, comparative study of two strategies of
      antibiotic use. SETTING: Two medical intensive care units of a university
      hospital. PATIENTS: A total of 346 patients admitted for >or=48 hrs to two
      separate medical intensive care units during an 8-month period. INTERVENTIONS:
      Patients, who according to the attending physician's judgment required an anti
      Pseudomonas regimen, were assigned to receive cefepime/ceftazidime,
      ciprofloxacin, a carbapemen, or piperacillin-tazobactam in this order. "Cycling"
      was accomplished by prescribing one of these antibiotics during 1 month each.
      "Mixing" was accomplished by using the same order of antibiotic administration on
      consecutive patients. Interventions were carried out during two successive 4
      month periods, starting with mixing in one unit and cycling in the other.
      MEASUREMENTS AND MAIN RESULTS: Swabbing of nares, pharynx, and rectum and culture
      of respiratory secretions were obtained thrice weekly. The main outcome variable
      was the proportion of patients acquiring enteric or nonfermentative Gram-negative
      bacilli resistant to the antibiotics under intervention. The scheduled cycling of
      antibiotics was only partially successful. Although the expected antibiotic was
      the most prevalent anti-Pseudomonas agent used within the corresponding period,
      it never accounted for >45% of all anti-Pseudomonas antimicrobials administered.
      During mixing, a significantly higher proportion of patients acquired a strain of
      Pseudomonas aeruginosa resistant to cefepime (9% vs. 3%, p = .01), and there was
      a trend toward a more frequent acquisition of resistance to ceftazidime (p =
      .06), imipenem (p = .06), and meropenem (p = .07). No differences in the rate of
      acquisition of potentially resistant Gram-negative bacilli or incidence of
      intensive care unit-acquired infections and infections due to particular
      organisms were observed. CONCLUSIONS: In critically ill medical patients, a
      strategy of monthly rotation of anti-Pseudomonas beta-lactams and ciprofloxacin
      may perform better than a strategy of mixing in the acquisition of P. aeruginosa
      resistant to selected beta-lactams.

PMID- 16424712
TI  - Prognostic implications of hyperlactatemia, multiple organ failure, and systemic
      inflammatory response syndrome in patients with acetaminophen-induced acute liver
      failure.
AB  - OBJECTIVE: Hyperlactatemia has been suggested as a prognostic marker in
      acetaminophen-induced fulminant hepatic failure, and a modification of the King's
      College Hospital criteria to incorporate arterial lactate measurements has
      recently been proposed. The aims of the present study were to further evaluate
      arterial lactate as a prognostic marker in acetaminophen-induced fulminant
      hepatic failure and to analyze its relationship to known causes of
      hyperlactatemia such as multiple organ failure and inflammation. DESIGN: Data
      were collected early after admission and again at the time of onset of grade 3-4
      hepatic encephalopathy from acetaminophen-induced fulminant hepatic failure.
      Multiple organ failure and inflammatory response were assessed by the sequential
      organ failure assessment (SOFA) score and manifestation of the severe
      inflammatory response syndrome (SIRS), respectively. SETTING: A specialized liver
      intensive care unit at a tertiary liver center. PATIENTS: One hundred and one
      consecutive patients with acetaminophen-induced fulminant hepatic failure and
      grade 3-4 hepatic encephalopathy. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Arterial lactate was higher in nonsurvivors than in survivors both early
      after admission (9.8 +/- 6.5 mmol/L vs. 5.2 +/- 4.2 mmol/L, p = .00004) and at
      the time of onset of hepatic encephalopathy (6.9 +/- 5.6 mmol/L vs. 3.2 +/- 2.0
      mmol/L, p < .00001). At both time points, arterial lactate significantly
      correlated with SOFA score and the number of SIRS components fulfilled. Applying
      the lactate modification of the King's College Hospital criteria increased their
      sensitivity but reduced their specificity to <50%. CONCLUSIONS: The study
      confirmed arterial lactate as a prognostic marker in acetaminophen-induced
      fulminant hepatic failure. Arterial lactate correlated with SOFA score and with
      the number of SIRS components fulfilled. The lactate modification of the King's
      College Hospital criteria showed no obvious advantages over the existing
      selection criteria.

PMID- 16424713
TI  - Sepsis in European intensive care units: results of the SOAP study.
AB  - OBJECTIVE: To better define the incidence of sepsis and the characteristics of
      critically ill patients in European intensive care units. DESIGN: Cohort,
      multiple-center, observational study. SETTING: One hundred and ninety-eight
      intensive care units in 24 European countries. PATIENTS: All new adult admissions
      to a participating intensive care unit between May 1 and 15, 2002. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Demographic data, comorbid diseases, and
      clinical and laboratory data were collected prospectively. Patients were followed
      up until death, until hospital discharge, or for 60 days. Of 3,147 adult
      patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of
      these patients had sepsis on admission. In patients with sepsis, the lung was the
      most common site of infection (68%), followed by the abdomen (22%). Cultures were
      positive in 60% of the patients with sepsis. The most common organisms were
      Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas
      species (14%), and Escherichia coli (13%). Pseudomonas species was the only
      microorganism independently associated with increased mortality rates. Patients
      with sepsis had more severe organ dysfunction, longer intensive care unit and
      hospital lengths of stay, and higher mortality rate than patients without sepsis.
      In patients with sepsis, age, positive fluid balance, septic shock, cancer, and
      medical admission were the important prognostic variables for intensive care unit
      mortality. There was considerable variation between countries, with a strong
      correlation between the frequency of sepsis and the intensive care unit mortality
      rates in each of these countries. CONCLUSIONS: This large pan-European study
      documents the high frequency of sepsis in critically ill patients and shows a
      close relationship between the proportion of patients with sepsis and the
      intensive care unit mortality in the various countries. In addition to age, a
      positive fluid balance was among the strongest prognostic factors for death.
      Patients with intensive care unit acquired sepsis have a worse outcome despite
      similar severity scores on intensive care unit admission.

PMID- 16424714
TI  - Effects of prolonged intensive care unit stay on quality of life and long-term
      survival after transthoracic esophageal resection.
AB  - OBJECTIVE: There are few prospective data on the effects of prolonged intensive
      care unit stay on the quality of life and long-term survival of a homogeneous
      patient population. Therefore, the aims of this prospective study were a) to
      describe the quality of life in patients after having a transthoracic esophageal
      resection; and b) to analyze the influences of a prolonged intensive care unit
      stay on quality of life and survival in patients after esophageal cancer
      resection who survived to hospital discharge. DESIGN: Prospective study. SETTING:
      Medical center. PATIENTS: The study population consisted of 109 patients
      undergoing a transthoracic resection for adenocarcinoma of the middistal
      esophagus or gastric cardia between April 1994 and February 2000. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: A comparison was made between patients
      staying <or=5 days vs. >or=6 days in the intensive care unit and also <or=2 days
      vs. >or=14 days. Quality of life was assessed in all patients by mailed self
      report questionnaires at baseline (preoperatively), at 5 wks, and at 3, 6, 9, 12,
      18, 24, 30, and 36 months after surgery. Daily physical, emotional, and social
      functioning was assessed with the generic Medical Outcome Studies Short Form-20.
      Disease-specific quality of life was measured by an adapted Rotterdam Symptom
      Check List. Quality of life data were gathered between July 1994 and March 2003.
      Five of the 109 patients died in the hospital and were excluded from the
      analysis. All five of them were in the intensive care unit >or=6 days. Of the
      remaining 104 patients, 92 provided baseline scores. The data of the 92 patients
      were used for the quality of life analyses. For the clinicopathologic and
      survival analysis, the data of 104 hospital survivors were used. Patients spent a
      median of 5.5 days (range 0-71) in the intensive care unit. The Medical Outcome
      Studies Short Form-20 and the Rotterdam Symptom Check List measurements showed no
      clear differences in long-term quality of life between patients after a short vs.
      a prolonged postoperative intensive care unit period. The median overall survival
      in all patients was 2.0 yrs (range 0.1-8.0). Median overall survival in patients
      staying in the intensive care unit <or=5 days was 1.9 yrs (range 0.3-7.4 yrs) vs.
      2.7 yrs (range 0.9-7.2 yrs) in patients staying >or=6 days (p = .9, log-rank
      test). Median overall survival in patients staying in the intensive care unit
      <or=2 days was 1.7 yrs (range 1.2-2.6 yrs) vs. 2.0 yrs (range 0.2-3.8 yrs) in
      patients staying >or=14 days (p = .74, log-rank test). CONCLUSIONS: For patients
      who survived to hospital discharge after transthoracic esophagectomy, there was
      no difference in long-term quality of life or survival between those submitted to
      the intensive care unit for a short period vs. a long period.

PMID- 16424715
TI  - Relationship between cardiopulmonary resuscitation and injuries of the cardiac
      conduction system: pathological features and pathogenesis of such injuries.
AB  - OBJECTIVE: The purpose of this study was to assess the incidence, features, and
      pathogenesis of microscopic injuries to the cardiac conduction system caused by
      cardiopulmonary resuscitation. DESIGN: : Prospective study. SETTING: Autopsy unit
      of the university. PATIENTS: Victims who had been transferred to the emergency
      room due to cardiac arrest arising from nontraumatic cause plus age-matched
      control patients. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The cardiac
      conduction system of 80 hearts without gross injury from patients who had
      received cardiopulmonary resuscitation due to nontraumatic causes was examined.
      Of these 80 patients, seven (9%) showed fresh injuries, including a lesion that
      had gone unreported in the previous literature. Localized hemorrhage without
      inflammatory reaction was evident in six of these patients. Three of the six
      patients showed hemorrhage in the sinoatrial node, whereas the other three
      patients showed hemorrhage in the atrioventricular conduction system. The
      remaining one patient showed localized dissection of the atrioventricular node
      artery with the appearance of red blood cells in the false lumen. There was no
      significant difference with regard to age, gender, cause of cardiopulmonary
      arrest, whether victim had received electrical shock treatment, whether victim
      had received anticoagulants, and the duration of cardiopulmonary resuscitation
      between the seven patients with fresh injuries and the other 73 patients.
      Fracture of the sternum or rib was found in only one of the seven patients but in
      14 of the 73 patients. No pathologic lesions were found in the 30 control
      patients who did not receive cardiopulmonary resuscitation. CONCLUSIONS: It can
      be presumed that injuries to the conduction system do occur in limited regions
      during cardiopulmonary resuscitation. Minute differences in the location of the
      cardiac silhouette or cardiac conduction system also need to be considered,
      rather than just the severity of force to the anterior chest, when determining
      the pathogenesis of these injuries.

PMID- 16424716
TI  - Repeated pulse of methylprednisolone and cyclophosphamide with continuous
      dexamethasone therapy for patients with severe paraquat poisoning.
AB  - OBJECTIVE: Paraquat is widely used in the world, and all treatments for paraquat
      poisoning have been unsuccessful. Many patients have died of paraquat poisoning
      in developing countries. A novel anti-inflammation method was developed to treat
      severe paraquat-poisoned patients with >50% to <90% predictive mortality: initial
      pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide
      (15 mg/kg/day for 2 days), followed by dexamethasone 20 mg/day until Pao2 was
      >11.5 kPa (80 mm Hg) and repeated pulse therapy with methylprednisolone (1 g/day
      for 3 days) and cyclophosphamide (15 mg/kg/day for 1 day), which was repeated if
      Pao2 was <8.64 kPa (60 mm Hg). DESIGN: Randomized controlled trial. SETTING:
      Academic medical center in Taiwan. PATIENTS: Twenty-three paraquat-poisoned
      patients with >50% and <90% predictive mortality assessed by plasma paraquat
      levels were prospectively and randomly assigned to the control and study groups
      at a proportion of 1:2. INTERVENTIONS: The control group received conventional
      therapy and the study group received the novel repeated pulse treatment with long
      term steroid therapy. MEASUREMENTS AND MAIN RESULTS: We measured patient
      mortality during the study period. There was not a different distribution of
      basal variables between the two study groups. The mortality rate (85.7%, six of
      seven) of the control group was higher than that of the study group (31.3%, five
      of 16; p = .0272). CONCLUSIONS: The novel anti-inflammatory therapy reduces the
      mortality rate for patients with severe paraquat poisoning.

PMID- 16424717
TI  - Canadian survey of the use of sedatives, analgesics, and neuromuscular blocking
      agents in critically ill patients.
AB  - OBJECTIVES: To characterize the perceived utilization of sedative, analgesic, and
      neuromuscular blocking agents, the use of sedation scales, algorithms, and daily
      sedative interruption in mechanically ventilated adults, and to define clinical
      factors that influence these practices. DESIGN: Cross-sectional mail survey.
      PARTICIPANTS: Canadian critical care practitioners. MEASUREMENTS AND MAIN
      RESULTS: A total of 273 of 448 eligible physicians (60%) responded. Respondents
      were well distributed with regard to age, years of practice, specialist
      certification, size of intensive care unit and hospital, and location of
      practice. Twenty-nine percent responded that a protocol/care pathway/guideline
      for the use of sedatives or analgesics is currently in use in their intensive
      care unit. Daily interruption of continuous infusions of sedatives or analgesics
      is practiced by 40% of intensivists. A sedation scoring system is used by 49% of
      respondents. Of these, 67% use the Ramsay scale, 10% use the Sedation-Agitation
      Scale, 9% use the Glasgow Coma Scale, and 8% use the Motor Activity Assessment
      Scale. Only 3.7% of intensivists use a delirium scoring system in their intensive
      care units. Only 22% of respondents currently have a protocol for the use of
      neuromuscular blocking agents in their intensive care unit, and 84% of
      respondents use peripheral nerve stimulation for monitoring. In patients
      receiving neuromuscular blocking agents for >24 hrs, 63.7% of respondents
      discontinue the neuromuscular blocking agent daily. Intensivists working in
      university-affiliated hospitals are more likely to employ a sedation protocol and
      scale (p < .0001), as are intensivists working in larger intensive care units
      (>or=15 beds, p < .01). Intensivists with anesthesiology training (and no formal
      critical care training) are more likely to use a protocol and sedation scale, and
      critical care-trained intensivists are more likely to use daily interruption.
      Younger physicians (<40 yrs) are more likely to practice daily interruption (p =
      .0092). CONCLUSIONS: There is significant variation in critical care sedation,
      analgesia, and neuromuscular blockade practice. Given the potential effect of
      practices regarding these medications on patient outcome, future research and
      educational efforts related to evidence-based protocols for the use of these
      agents in mechanically ventilated patients might be worthwhile.

PMID- 16424718
TI  - Parenterally administered dipeptide alanyl-glutamine prevents worsening of
      insulin sensitivity in multiple-trauma patients.
AB  - BACKGROUND: Dipeptide alanyl-glutamine is a commonly used substrate in major
      trauma patients. Its importance and effects are widely discussed; as yet, it has
      not been elucidated whether its administration influences glucose homeostasis.
      OBJECTIVE: We studied the effect of alanyl-glutamine administration on insulin
      resistance. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive
      care unit of a tertiary level hospital. PATIENTS: Multiple-trauma patients.
      INTERVENTIONS: Patients were randomized into two groups and assigned to receive
      parenterally an equal dose of amino acids either with alanyl-glutamine in the
      dose of 0.4 g x kg body weight(-1) x 24 hrs(-1) (group AG) or without alanyl
      glutamine (control group C). This regimen started 24 hrs after injury and
      continued for 7 days. To assess insulin sensitivity, we performed an euglycemic
      clamp on day 4 and day 8 after injury. MEASUREMENTS AND MAIN RESULTS: We
      randomized 40 patients, 20 into each group. At day 4, insulin-mediated glucose
      disposal was higher in group AG (2.4 +/- 0.7 mg x kg(-1) x min(-1) glucose), with
      significant difference from group C (1.9 +/- 0.6 mg x kg(-1) x min(-1), p =
      .044). At day 8, glucose disposal was higher in group AG (2.2 +/- 0.7 mg x kg(-1)
      x min(-1) glucose), with significant difference in comparison with group C (1.2
      +/- 0.6, p < .001). Diminution of the main glucose homeostasis variables in group
      C between days 4 and 8 of the study was statistically significant (p < .001);
      however, differences in these variables in group AG were without statistical
      significance. CONCLUSIONS: Parenteral supplementation of alanyl-glutamine
      dipeptide was associated with better insulin sensitivity in multiple-trauma
      patients.

PMID- 16424719
TI  - Improved nurse job satisfaction and job retention with the transition from a
      "mandatory consultation" model to a "semiclosed" surgical intensive care unit: a
      1-year prospective evaluation.
AB  - OBJECTIVE: The change from a "mandatory consultation" to a "semiclosed" surgical
      intensive care unit (SICU) model will impact nurses considerably. We hypothesize
      that nurse job satisfaction, job turnover rates, and hospital costs for temporary
      agency nurses will improve and these improvements will be more dramatic in SICU
      sections with greater involvement of a dedicated surgical critical care service
      (SCCS). DESIGN: Prospective longitudinal survey. SETTING: Tertiary-care
      university hospital. SUBJECTS: SICU staff nurses. INTERVENTIONS: Change from
      mandatory consultation to semiclosed SICU. MEASUREMENTS AND MAIN RESULTS: We
      surveyed SICU nurses during the year-long transition to a semiclosed SICU service
      (five time points, 3-month intervals). The first four surveys included ten
      questions on nurse job satisfaction. The final survey included two additional
      questions. All questions were on a 5-point Likert scale (1 = strongly disagree to
      5 = strongly agree). Nurse job turnover rates and money spent on agency nurses
      were compared over time; 503 of a possible 914 surveys were completed (55%
      overall return rate). Nurse job satisfaction scores significantly improved over
      time for all questions (p < .05). Hospital spending on agency nurses decreased
      significantly (p = .0098). The yearly nurse job turnover rate dropped from 25% to
      16% (p = .15). The scores for both year-end statements ("I am more satisfied with
      my job now than 1 year ago" and "The SCCS management of all orders has improved
      my job satisfaction") were significantly higher in sections with greater SCCS
      involvement (p = .0070 and p < .0001). CONCLUSIONS: Nurse job satisfaction
      improved significantly with the transition to a semiclosed SICU. This higher
      satisfaction was associated with a significant decrease in spending on temporary
      agency nurses and a trend toward increased staff nurse job retention. SICU
      sections with greater SCCS involvement had more dramatic improvements. This
      semiclosed SICU model may help retain SICU nurses in a competitive job market in
      which experienced nurses are in short supply.

PMID- 16424721
TI  - The effects of dobutamine on microcirculatory alterations in patients with septic
      shock are independent of its systemic effects.
AB  - OBJECTIVE: To evaluate the effects of dobutamine on microcirculatory blood flow
      alterations in patients with septic shock. DESIGN: Prospective, open-label study.
      SETTING: A 31-bed, medico-surgical intensive care unit of a university hospital.
      PATIENTS: Twenty-two patients with septic shock. INTERVENTIONS: Intravenous
      administration of dobutamine (5 mug/kg.min) for 2 hrs (n = 22) followed by the
      addition of 10 M acetylcholine (topically applied, n = 10). MEASUREMENTS AND MAIN
      RESULTS: Complete hemodynamic measurements were obtained before and after
      dobutamine administration. In addition, the sublingual microcirculation was
      investigated with an orthogonal polarization spectral imaging technique before
      and after dobutamine administration and after topical application of
      acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 +/-
      15 to 67 +/- 11%, p = .001), but with large individual variation, whereas
      capillary density remained stable. The addition of topical acetylcholine
      completely restored capillary perfusion (98 +/- 1%, p = .001) and capillary
      density. The changes in capillary perfusion during dobutamine administration were
      not related to changes in cardiac index (p = .45) or arterial pressure (p = .29).
      Interestingly, the decrease in lactate levels was proportional to the improvement
      in capillary perfusion (y = 0.07 - 0.02x, r = .46, p = .005) but not to changes
      in cardiac index (p = .55). CONCLUSIONS: The administration of 5 mug/kg.min
      dobutamine can improve but not restore capillary perfusion in patients with
      septic shock. These changes are independent of changes in systemic hemodynamic
      variables.

PMID- 16424720
TI  - Feasibility and effects of the semirecumbent position to prevent ventilator
      associated pneumonia: a randomized study.
AB  - CONTEXT: Reducing aspiration of gastric contents by placing mechanically
      ventilated patients in a semirecumbent position has been associated with lower
      incidences of ventilator-associated pneumonia (VAP). The feasibility and efficacy
      of this intervention in a larger patient population, however, are unknown.
      OBJECTIVE: Assessment of the feasibility of the semirecumbent position for
      intensive care unit patients and its influence on development of VAP. DESIGN: In
      a prospective multicentered trial, critically ill patients undergoing mechanical
      ventilation were randomly assigned to the semirecumbent position, with a target
      backrest elevation of 45 degrees , or standard care (i.e., supine position) with
      a backrest elevation of 10 degrees . MAIN OUTCOME MEASURES: Backrest elevation
      was measured continuously during the first week of ventilation with a monitor
      linked device. A deviation of position was defined as a change of the randomized
      position >5 degrees . Diagnosis of VAP was made by quantitative cultures of
      samples obtained by bronchoscopic techniques. RESULTS: One hundred nine patients
      were assigned to the supine group and 112 to the semirecumbent group. Baseline
      characteristics were comparable for both groups. Average elevations were 9.8
      degrees and 16.1 degrees at day 1 and day 7, respectively, for the supine group
      and 28.1 degrees and 22.6 degrees at day 1 and day 7, respectively, for the
      semirecumbent group (p < .001). The target semirecumbent position of 45 degrees
      was not achieved for 85% of the study time, and these patients more frequently
      changed position than supine-positioned patients. VAP was diagnosed in eight
      patients (6.5%) in the supine group and in 13 (10.7%) in the semirecumbent group
      (NS), after a mean of 6 (range, 3-9) and 7 (range, 3-12) days, respectively.
      There were no differences in numbers of patients undergoing enteral feeding,
      receiving stress ulcer prophylaxis, or developing pressure sores or in mortality
      rates or duration of ventilation and intensive care unit stay between the groups.
      CONCLUSIONS: The targeted backrest elevation of 45 degrees for semirecumbent
      positioning was not reached in the conditions of the present randomized study.
      The achieved difference in treatment position (28 degrees vs. 10 degrees ) did
      not prevent the development of VAP.

PMID- 16424722
TI  - The cuff-leak test is a simple tool to verify severe laryngeal edema in patients
      undergoing long-term mechanical ventilation.
AB  - OBJECTIVE: The cuff-leak test has been proposed as a simple tool to clinically
      predict stridor or respiratory distress secondary to laryngeal edema following
      extubation. However, the true incidence of laryngeal edema in patients on long
      term mechanical ventilation is uncertain. The relationship between upper airway
      obstruction (detected by video bronchoscopy) and the cuff-leak test value for
      patients with prolonged translaryngeal intubation during percutaneous
      dilatational tracheostomy (PDT) was investigated. DESIGN: Prospective, clinical
      investigation. SETTING: Intensive care unit of a university hospital. PATIENTS:
      Ninety-five patients with prolonged translaryngeal intubation requiring PDT were
      enrolled during a 12-month period. INTERVENTIONS: Cuff-leak test, PDT, video
      bronchoscopy. MEASUREMENTS AND MAIN RESULTS: The average duration of
      translaryngeal intubation was 28.1 +/- 17.6 days. The incidence of severe
      laryngeal edema was 36.8% (35/95). We chose 140 mL as the threshold cuff-leak
      volume below which edema is indicated. The rate of cuff-leak test positivity was
      38.9% (37/95). The sensitivity and the specificity of the test were 88.6% and
      90.0%, respectively. The positive and negative predictive values were 83.8% and
      93.1%, respectively. Patients who developed severe laryngeal edema had a smaller
      leak volume than those who did not, expressed in absolute values (53.9 +/- 56.2
      vs. 287.9 +/- 120.0 mL; p < .001) or in relative values (10.1 +/- 10.2 vs. 55.3
      +/- 22.7%, p < .001). The occurrence of severe laryngeal edema was not associated
      with age, gender, body weight, respiratory failure due to pneumonia, duration of
      translaryngeal intubation, endotracheal tube diameter, Acute Physiology and
      Chronic Health Evaluation II score, or history of self-extubation. CONCLUSIONS: A
      reduced cuff-leak volume measured before PDT may signal the presence of severe
      laryngeal edema in patients on long-term mechanical ventilation.

PMID- 16424723
TI  - Medication errors and adverse drug events in an intensive care unit: direct
      observation approach for detection.
AB  - OBJECTIVE: To determine the incidence and preventability of medication errors and
      potential/actual adverse drug events. To evaluate system failures leading to
      error occurrence. DESIGN: Prospective, direct observation study. SETTING:
      Tertiary care academic medical center. PATIENTS: Patients in a medical/surgical
      intensive care unit. INTERVENTIONS: Observers would intervene only in the event
      that the medication error would cause substantial patient harm or discomfort.
      MEASUREMENTS AND MAIN RESULTS: The observers identified 185 incidents during a
      pilot period and four phases totaling 16.5 days (33 12-hr shifts). Two
      independent evaluators concluded that 13 of 35 (37%) actual adverse drug events
      were nonpreventable (i.e., not medication errors). An additional 40 of the
      remaining 172 medication errors were judged not to be clinically important. Of
      the 132 medication errors classified as clinically important, 110 (83%) led to
      potential adverse drug events and 22 (17%) led to actual, preventable adverse
      drug events. There was one error (i.e., resulting in a potential or actual,
      preventable adverse drug event) for every five doses of medication administered.
      The potential adverse drug events mostly occurred in the administration and
      dispensing stages of the medication use process (34% in each); all of the actual,
      preventable adverse drug events occurred in the prescribing (77%) and
      administration (23%) stages. Errors of omission accounted for the majority of
      potential and actual, preventable adverse drug events (23%), followed by errors
      due to wrong dose (20%), wrong drug (16%), wrong administration technique (15%),
      and drug-drug interaction (10%). CONCLUSIONS: Using a direct observation
      approach, we found a higher incidence of potential and actual, preventable
      adverse drug events and an increased ratio of potential to actual, preventable
      adverse drug events compared with studies that used chart reviews and solicited
      incident reporting. All of the potential adverse drug events and approximately
      two thirds of the actual adverse drug events were judged to be preventable. There
      was one preventable error for every five doses of medication administered; most
      errors were due to dose omission, wrong dose, wrong drug, wrong technique, or
      interactions.

PMID- 16424724
TI  - Graft protein C entrapment is associated with reduced phagocyte activation during
      reperfusion in human liver transplantation.
AB  - OBJECTIVE: To explore the potential anti-inflammatory role of protein C pathway
      in ischemia-reperfusion injury during liver transplantation. DESIGN: Prospective,
      observational clinical study. SETTING: Tertiary teaching hospital. PATIENTS:
      Fifty adult patients undergoing liver transplantation for acute liver failure or
      chronic liver disease. INTERVENTIONS: To assess changes occurring across the
      transplanted liver, samples of blood entering and leaving the graft were obtained
      simultaneously from portal and hepatic veins. Plasma protein C and activated
      protein C levels, neutrophil and monocyte CD11b and L-selectin expression, and
      leukocyte differential counts were measured. Postoperative liver function and
      outcome of transplantation were recorded. MEASUREMENTS AND MAIN RESULTS: During
      reperfusion, protein C became entrapped within the graft (portal vein 49% [20
      96%]; graft caval effluent 25% [12-76%], p < .001), without concomitant activated
      protein C outflow from the graft. Simultaneously, marked neutrophil and monocyte
      activation occurred within the graft. Enhanced hepatic protein C entrapment was
      associated with reduced neutrophil and monocyte activation (R = .377, p = .011; R
      = .389, p = .008, respectively) during reperfusion. CONCLUSIONS: Protein C
      entrapment occurs immediately during reperfusion in the graft without concomitant
      activated protein C release, suggesting a shortage of activated protein C in the
      reperfused graft. The ongoing inflammatory response during reperfusion may lead
      to protein C and activated protein C utilization within the graft. Indeed,
      hepatic protein C entrapment is associated with reduced hepatic phagocyte
      activation, suggesting a regulatory role for protein C pathway in hepatic
      reperfusion in human liver transplantation.

PMID- 16424725
TI  - Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension
      after traumatic brain injury.
AB  - OBJECTIVE: Two series of experiments were designed to evaluate whether early
      arginine vasopressin improves acute outcome following resuscitation from
      traumatic brain injury and severe hemorrhagic hypotension. DESIGN: Prospective
      randomized, blinded animal study. SETTING: University laboratory. SUBJECTS:
      Thirty-three swine. INTERVENTIONS: In series 1 (n = 19), after traumatic brain
      injury with hemorrhage and 12 mins of shock (mean arterial pressure approximately
      20 mm Hg), survivors (n = 16) were initially resuscitated with 10 mL/kg
      crystalloid. After 30 mins, crystalloid and blood with either 0.1 unit x kg(-1) x
      hr(-1) arginine vasopressin or placebo was titrated to a mean arterial pressure
      target >or=60 mm Hg. After 90 mins, all received mannitol and the target was
      cerebral perfusion pressure >or=60 mm Hg. To test cerebrovascular function, 7.5%
      inhaled CO2 was administered periodically. In series 2 (n = 14), the identical
      protocol was followed except the shock period was 20 mins and survivors (n = 10)
      received a bolus of either arginine vasopressin (0.2 units/kg) or placebo during
      the initial fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: In series 1, by
      300 mins after traumatic brain injury with arginine vasopressin (n = 8) vs.
      placebo (n = 8), the fluid and transfusion requirements were reduced (both p <
      .01), intracranial pressure was improved (11 +/- 1 vs. 23 +/- 2 mmHg; p < .0001),
      and the CO2-evoked intracranial pressure elevation was reduced (7 +/- 2 vs. 26 +/
      3 mm Hg, p < .001), suggesting improved compliance. In series 2, with arginine
      vasopressin vs. placebo, cerebral perfusion pressure was more rapidly corrected
      (p < .05). With arginine vasopressin, five of five animals survived 300 mins,
      whereas three of five placebo animals died. The survival time with placebo was 54
      +/- 4 mins (p < .05 vs. arginine vasopressin). CONCLUSIONS: Early supplemental
      arginine vasopressin rapidly corrected cerebral perfusion pressure, improved
      cerebrovascular compliance, and prevented circulatory collapse during fluid
      resuscitation of hemorrhagic shock after traumatic brain injury.

PMID- 16424726
TI  - Comparison of variable and conventional ventilation in a sheep saline lavage lung
      injury model.
AB  - OBJECTIVE: There has recently been considerable interest in alternative lung
      protective ventilation strategies such as variable ventilation (VV). We aimed at
      testing VV in a large animal lung injury model and exploring the mechanism of
      improvement in gas exchange seen with VV. DESIGN: Randomized, controlled
      comparative ventilation study. SETTING: Research laboratory at a veterinary
      hospital. SUBJECTS: Female sheep weighing 59.8 +/- 10.57 kg and excised calf
      lungs. INTERVENTIONS: In a sheep saline lavage model of lung injury, we applied
      VV, whereby tidal volume (VT) and frequency (f) varied on each breath. Sheep were
      randomized into one of two groups (VV, n = 7; or control, n = 6) and ventilated
      for 4 hrs with all mean ventilation settings matched. MEASUREMENTS AND MAIN
      RESULTS: Gas exchange, lung mechanics, and hemodynamic measures were recorded
      over the 4 hrs. VV sheep showed improvement in gas exchange (i.e., oxygenation
      and carbon dioxide elimination) and ventilation pressures (i.e., reduced mean and
      peak airway pressures) but control sheep did not. VV sheep also displayed lower
      lung elastance and mechanical heterogeneity in comparison with control sheep from
      2 to 4 hrs of ventilation. To study the mechanism behind improvements seen with
      VV, we examined the time course associated with the enhanced recruitment
      occurring during VV in eight saline-lavaged excised calf lungs. We found that the
      recruitment associated with a larger VT during VV lasted over 200 secs, nearly an
      order of magnitude greater than the average time interval between large VT
      deliveries during VV. CONCLUSIONS: The application of VV in a large animal model
      of lung injury results in improved gas exchange and superior lung mechanics in
      comparison with CV that can be explained at least partially by the long-lasting
      effects of the recruitments occurring during VV.

PMID- 16424727
TI  - Increases in tissue Pco2 during circulatory shock reflect selective decreases in
      capillary blood flow.
AB  - OBJECTIVES: Tissue Pco2 reflects metabolic alterations due to circulatory failure
      during circulatory shock. This study addresses simultaneous changes in gastric
      and buccal tissue Pco2 with changes in microcirculatory blood flow in a rat model
      of circulatory shock induced by cecal ligation and puncture. DESIGN: Prospective
      controlled laboratory study. SETTING: University-affiliated research laboratory.
      SUBJECTS: Male breeder Sprague-Dawley rats. INTERVENTIONS: Induction of
      polymicrobial, abdominal sepsis by cecal ligation and puncture. MEASUREMENTS AND
      MAIN RESULTS: Tissue Pco2 was continuously measured with the aid of a miniature
      carbon dioxide electrode. Using orthogonal polarization spectral imaging,
      recordings of the microcirculation were taken at baseline and hourly intervals
      until death and compared with sham-operated animals. Gastric and buccal tissue
      Pco2 values progressively increased in animals after cecal ligation and puncture
      and terminated in death. Microcirculatory blood flow in vessels >20 microm was
      well preserved during progression of shock, whereas there was an early and
      progressive decrease in microcirculatory blood flow in vessels <20 microm, mostly
      representing capillaries. Tissue Pco2, the tissue Pco2-Paco2 gradient, and blood
      flow in vessels <20 microm were highly correlated. This contrasted with sham
      control animals in which no significant hemodynamic, blood gas, lactate,
      microcirculatory, and tissue Pco2 abnormalities were observed. CONCLUSIONS: These
      observations suggest that microcirculatory failure in capillaries appears as an
      early defect in close association with anaerobic metabolism during progression of
      circulatory shock in an animal model of septic peritonitis.

PMID- 16424728
TI  - Propofol improves endothelial dysfunction and attenuates vascular superoxide
      production in septic rats.
AB  - OBJECTIVE: To determine the effects of propofol on vascular functions, plasma and
      endothelium-derived nitric oxide (EDNO), vascular NO, and cyclic guanosine
      monophosphate (cGMP), as well as vascular production of superoxide anion (O2*-),
      in septic animals. DESIGN: Prospective, multiexperimental, randomized, controlled
      studies. SETTING: University research laboratory. SUBJECTS: Male adult Sprague
      Dawley rats weighing 350-400 g. INTERVENTIONS: Cecal ligation and puncture (CLP),
      with and without propofol (25 mg/kg/hr) infusion, after sham or CLP (24 hrs
      postsurgery). MEASUREMENTS AND MAIN RESULTS: Plasma NOx, basal aortic NOx, and
      cGMP concentrations all increased, whereas acetylcholine-induced endothelium
      dependent relaxation (EDR), contractile response, and EDNO all decreased in CLP
      vs. sham rats (p < .001). Acetylcholine stimulated aortic NOx and cGMP
      significantly in sham and CLP-propofol (p < .01) but not CLP rats. Thus, propofol
      ameliorated the CLP-induced increases in plasma NOx, basal aortic NOx, and cGMP.
      It restored the CLP-induced impairment of EDR, EDNO, and acetylcholine-stimulated
      aortic NOx and cGMP levels. More O2*- production (measured by lucigenin-enhanced
      chemiluminescence) was noted in carotid arteries from CLP vs. sham rats (p <
      .001). Nicotinamide adenine dinucleotide (NADH; 1 mM) stimulated O2*- production
      in all rings, with significantly more increase in CLP vs. sham (p < .001).
      Propofol attenuated the excessive increase in O2*- production of CLP rings.
      CONCLUSIONS: Propofol treatment attenuated the overproduction of NO and O2*-,
      thus restoring the acetylcholine-responsive NO-cGMP pathway in CLP-induced
      sepsis. It also significantly improved the CLP-impaired EDR and EDNO in a
      parallel manner. These beneficial effects of propofol could be accounted for by
      improvement of the disturbed NO/O2*- balance in sepsis.

PMID- 16424729
TI  - Toll-like receptor 4 signaling leads to neutrophil migration impairment in
      polymicrobial sepsis.
AB  - OBJECTIVE: We have documented an impaired neutrophil migration toward the
      infectious focus in severe sepsis. This phenomenon appears to be mediated by
      nitric oxide, the release of which is stimulated by circulating inflammatory
      cytokines released by immune cells after stimulation by bacteria and/or their
      products. Toll-like receptor 4 (TLR4) is the major recognition receptor for
      lipopolysaccharide, a component of Gram-negative bacterial cell walls. In the
      present study, we investigated whether TLR4 is involved in the failure of
      neutrophil migration in mice subjected to polymicrobial or Gram-negative sepsis.
      DESIGN: Controlled animal study. SETTING: University research laboratory.
      SUBJECTS: Male C3H/HeJ (TLR4-deficient) and C3H/HePas (TLR4-normal) mice.
      INTERVENTIONS: Mice were subjected to sublethal or lethal polymicrobial sepsis,
      both induced by cecal ligation and puncture or intraperitoneal polymicrobial
      inoculation, and subjected to sublethal Gram-negative sepsis induced by
      intraperitoneal Salmonella typhimurium inoculation (GNI). Survival was monitored
      for 5 days. In separate experiments, mice were killed 6 hrs after sepsis
      induction, and intraperitoneal neutrophil migration, bacteremia, lung neutrophil
      sequestration, and levels of cytokines, chemokines, and nitrate were evaluated.
      MEASUREMENTS AND RESULTS: TLR4-deficient (C3H/HeJ) mice presented incapacity to
      promote neutrophil recruitment to the infectious site after sublethal GNI,
      resulting in high mortality. However, TLR4 signaling is not essential to display
      neutrophil migration in sublethal polymicrobial sepsis induced by both cecal
      ligation and puncture and polymicrobial inoculation models, but surprisingly, it
      is crucial to establish the impairment of neutrophil migration in lethal
      polymicrobial sepsis, since TLR4-deficient mice that underwent lethal cecal
      ligation and puncture or polymicrobial inoculation did not present failure of
      neutrophil migration to infectious focus. As a consequence, these animals
      presented low bacteremia and a high survival rate and did not display systemic
      inflammation, determined by high levels of circulating cytokines and lung
      neutrophil sequestration and chemokine production. CONCLUSION: These results
      highlight the harmful role of TLR4 signaling in polymicrobial severe sepsis.

PMID- 16424730
TI  - Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute
      lung injury in the rat.
AB  - OBJECTIVES: Interventions that reduce the generation or the effects of reactive
      oxygen species exert controversial effects in animal models of lung injury, and
      these could be secondary to the pro-oxidant effects of antioxidants generally by
      their interaction with iron. We here describe the effects of N-acetylcysteine,
      deferoxamine, or both in the treatment of acute lung injury induced by
      intratracheal lipopolysaccharide injection. DESIGN: Prospective, randomized,
      controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male
      Wistar rats, weighing 200-250 g. INTERVENTIONS: Rats exposed intratracheally to
      lipopolysaccharide were treated with N-acetylcysteine (20 mg/kg subcutaneously 3,
      6, and 12 hrs after lipopolysaccharide instillation), deferoxamine (20 mg/kg
      subcutaneously 3 hrs after lipopolysaccharide instillation), N-acetylcysteine (20
      mg/kg, 3, 6, and 12 hrs after lipopolysaccharide instillation) plus deferoxamine
      (20 mg/kg 3 hrs after lipopolysaccharide instillation), or vehicle. MEASUREMENTS
      AND MAIN RESULTS: Acute lung injury was induced by intratracheal instillation of
      lipopolysaccharide in Wistar rats. The animals were randomly divided into five
      groups: group 1, control with instillation of isotonic saline; group 2,
      lipopolysaccharide treated with saline; group 3, lipopolysaccharide treated with
      N-acetylcysteine; group 4, lipopolysaccharide treated with deferoxamine; and
      group 5, lipopolysaccharide treated with N-acetylcysteine plus deferoxamine.
      Several times after lipopolysaccharide instillation, the rats were killed and a
      bronchoalveolar lavage was performed to determine thiobarbituric acid reactive
      species, protein carbonyls, superoxide dismutase and catalase activities,
      mitochondrial superoxide production (oxidative stress variables), the degree of
      the alveolar-capillary membrane compromise, and inflammatory infiltration.
      Samples from the lung were isolated and assayed for oxidative stress variables or
      histopathologic analyses. N-acetylcysteine plus deferoxamine decreased
      bronchoalveolar lavage fluid protein, inflammatory cells, oxidative damage
      variables, and proinflammatory cytokines. N-acetylcysteine plus deferoxamine
      treatment significantly attenuated lung oxidative damage, mitochondrial
      superoxide production, and histopathologic alterations after lipopolysaccharide
      instillation. CONCLUSIONS: Our data provide the first experimental demonstration
      that N-acetylcysteine plus deferoxamine decreases oxidative stress and
      mitochondrial dysfunction and limits inflammatory response and alveolar pathology
      induced by lipopolysaccharide in the rat.

PMID- 16424731
TI  - Dose-dependent influence of barbiturates but not of propofol on human leukocyte
      phagocytosis of viable Staphylococcus aureus.
AB  - OBJECTIVE: Deep sedation with barbiturates or propofol is a standard therapy for
      patients with critically elevated intracranial pressure. Such patients are prone
      to infectious complications, especially to pneumonias, which are most commonly
      caused by Staphylococcus aureus. Although various immunomodulatory effects of
      barbiturates have been described in vitro, their influence on the phagocytosis of
      viable S. aureus has yet to be investigated. Therefore, we examined the effects
      of thiopentone, methohexitone, and propofol on the phagocytosis of viable S.
      aureus. DESIGN: Laboratory study. SETTING: University laboratory. PATIENTS: Ten
      healthy volunteers aged 32.5 +/- 7 yrs. INTERVENTIONS: Blood sampling.
      MEASUREMENTS AND MAIN RESULTS: Whole blood samples were preincubated with
      different concentrations of thiopentone, methohexitone, and propofol, which is an
      isopropylphenol derivate. After viable S. aureus was added, phagocytosis was
      stopped at different time points. Leukocytes were then stained with monoclonal
      antibodies for flow cytometric analysis of granulocyte recruitment (ratio of
      ingesting granulocytes) and phagocytosis activity (fluorescence intensity of
      ingested bacteria). Both barbiturates inhibited granulocyte recruitment and
      phagocytosis activity in a dose-dependent manner, whereas propofol did not affect
      any of the investigated variables. At concentrations higher than 7.6 x 10(-3) M
      (for thiopentone, p < .008) and 1.1 x 10(-3) M (for methohexitone, p < .04),
      granulocyte recruitment and phagocytosis activity were significantly inhibited.
      The calculated inhibitory concentrations (IC50) of thiopentone for granulocyte
      recruitment and for phagocytosis activity were 1.3 x 10(-2) M and 1.1 x 10(-2) M,
      respectively. The corresponding values for methohexitone were 3.6 x 10(-3) M and
      1.1 x 10(-3) M. CONCLUSIONS: Our in vitro model points at substantially different
      effects of barbiturates and propofol on phagocytosis of S. aureus, which is one
      of the most important pathogens in patients who need neuroprotective therapy. The
      inhibitory effects of both barbiturates demonstrate a strong dose-dependency,
      with more pronounced effects for methohexitone. Impairment of phagocytosis
      activity was more pronounced than granulocyte recruitment.

PMID- 16424732
TI  - Role of tumor necrosis factor-alpha in myocardial dysfunction and apoptosis
      during hindlimb ischemia and reperfusion.
AB  - OBJECTIVE: Peripheral vascular surgery involving limb ischemia/reperfusion is
      associated with tumor necrosis factor-alpha production and an increased risk of
      cardiac complications. The objective of this study was to investigate the role of
      tumor necrosis factor-alpha in myocardial apoptosis and dysfunction following
      hindlimb ischemia/reperfusion. DESIGN: Randomized perspective animal study.
      SETTING: Research laboratory. SUBJECTS: Adults male tumor necrosis factor-alpha(
      /-) and littermate wild-type mice. INTERVENTIONS: Bilateral hindlimb
      ischemia/reperfusion was induced in wild-type and tumor necrosis factor-alpha(-/
      ) mice using tourniquet occlusion. After 2 hrs of hindlimb ischemia, the
      tourniquets were released, allowing reperfusion for 0.5-24 hrs. MEASUREMENTS AND
      MAIN RESULTS: In wild-type mice, hindlimb ischemia/reperfusion resulted in
      myocardial depression early during the reperfusion period (p < .05). These
      effects were temporally correlated with enhanced levels of myocardial and plasma
      tumor necrosis factor-alpha. All variables were restored to baseline levels by 24
      hrs of reperfusion. Myocardial apoptosis, assessed by cell death enzyme-linked
      immunosorbent assay, terminal deoxynucleotidyl transferase-mediated biotin-dUTP
      nick-end labeling staining, and caspase-3 activity, was also significantly higher
      at 6 hrs of reperfusion (p < .05) but returned to baseline levels by 24 hrs.
      Interestingly, cardiac dysfunction and myocardial apoptosis were abolished in
      tumor necrosis factor-alpha mice subjected to the same degree of hindlimb
      ischemia/reperfusion as the wild-type mice. Treatment of etanercept restored
      cardiac function in wild-type mice. CONCLUSIONS: Tumor necrosis factor-alpha
      contributes significantly to myocardial dysfunction and apoptosis in hindlimb
      ischemia/reperfusion. Although a causal link between myocardial apoptosis and
      cardiac dysfunction is not established, our study does suggest that tumor
      necrosis factor-alpha may be a potential therapeutic target for cardiac injury in
      clinical situations involving prolonged remote ischemia/reperfusion.

PMID- 16424733
TI  - Acute, transient hemorrhagic hypotension does not aggravate structural damage or
      neurologic motor deficits but delays the long-term cognitive recovery following
      mild to moderate traumatic brain injury.
AB  - OBJECTIVES: Posttraumatic hypotension is believed to increase morbidity and
      mortality in traumatically brain-injured patients. Using a clinically relevant
      model of combined traumatic brain injury with superimposed hemorrhagic
      hypotension in rats, the present study evaluated whether a reduction in mean
      arterial blood pressure aggravates regional brain edema formation, regional cell
      death, and neurologic motor/cognitive deficits associated with traumatic brain
      injury. DESIGN: Experimental prospective, randomized study in rodents. SETTING:
      Experimental laboratory at a university hospital. SUBJECTS: One hundred nineteen
      male Sprague-Dawley rats weighing 350-385 g. INTERVENTIONS: Experimental
      traumatic brain injury of mild to moderate severity was induced using the lateral
      fluid percussion brain injury model in anesthetized rats (n = 89). Following
      traumatic brain injury, in surviving animals one group of animals was subjected
      to pressure-controlled hemorrhagic hypotension, maintaining the mean arterial
      blood pressure at 50-60 mm Hg for 30 mins (n = 47). The animals were subsequently
      either resuscitated with lactated Ringer's solution (three times shed blood
      volume, n = 18) or left uncompensated (n = 29). Other groups of animals included
      those with isolated traumatic brain injury (n = 34), those with isolated
      hemorrhagic hypotension (n = 8), and sham-injured control animals receiving
      anesthesia and surgery alone (n = 22). MEASUREMENTS AND MAIN RESULTS: The
      withdrawal of 6-7 mL of arterial blood significantly reduced mean arterial blood
      pressure by 50% without decreasing arterial oxygen saturation or Pao2. Brain
      injury induced significant cerebral edema (p < .001) in vulnerable brain regions
      and cortical tissue loss (p < .01) compared with sham-injured animals. Neither
      regional brain edema formation at 24 hrs postinjury nor the extent of cortical
      tissue loss assessed at 7 days postinjury was significantly aggravated by
      superimposed hemorrhagic hypotension. Brain injury-induced neurologic deficits
      persisted up to 20 wks after injury and were also not aggravated by the
      hemorrhagic hypotension. Cognitive dysfunction persisted for up to 16 wks
      postinjury. The superimposition of hemorrhagic hypotension significantly delayed
      the time course of cognitive recovery. CONCLUSIONS: A single, acute hypotensive
      event lasting 30 mins did not aggravate the short- and long-term structural and
      motor deficits but delayed the speed of recovery of cognitive function associated
      with experimental traumatic brain injury.

PMID- 16424734
TI  - Oxime therapy and outcomes in human organophosphate poisoning: an evaluation
      using meta-analytic techniques.
AB  - OBJECTIVE: The status of oximes in human organophosphate poisoning is
      controversial. This analysis compares the outcomes of therapy with or without
      oximes. DESIGN: Quantitative analysis using meta-analytic techniques. METHODS:
      Controlled trials of oximes in human organophosphate poisoning were identified by
      search of MEDLINE and TOXLINE (1966 to May 2005) and review of published
      articles. MEASUREMENTS AND MAIN RESULTS: Of the 3,122 articles on organophosphate
      poisoning identified by electronic search, 116 related to oxime use in human
      organophosphate poisoning. Seven trials, including two randomized controlled
      trials, compared oximes with standard medical care. Varying dosage schedules of
      pralidoxime or obidoxime were used. The effects of oxime therapy on mortality
      rate, mechanical ventilation, incidence of intermediate syndrome, and need for
      intensive care therapy were analyzed and expressed as risk difference (positive
      values indicating oxime harm). The random effects estimator was reported because
      of underlying heterogeneity of treatment effects between study types. No
      statistically significant association of oxime therapy was demonstrated for
      either mortality (risk difference 0.09, 95% confidence interval -0.08 to 0.27),
      ventilatory requirements (risk difference 0.16, 95% confidence interval -0.07 to
      0.38), or the incidence of intermediate syndrome (risk difference 0.16, 95%
      confidence interval -0.12 to 0.45), although point estimates of effect suggested
      harm. An increased need for intensive care therapy (risk difference 0.19, 95%
      confidence interval 0.01 to 0.36) was apparent with oxime therapy. CONCLUSIONS:
      Based on the current available data on human organophosphate poisoning, oxime was
      associated with either a null effect or possible harm. The lack of current
      prospective randomized controlled trials, with appropriate patient
      stratification, mandates ongoing assessment of the role of oximes in
      organophosphate poisoning.

PMID- 16424735
TI  - Controversies in the management of aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: The care of patients with aneurysmal subarachnoid hemorrhage has
      evolved significantly with the advent of new diagnostic and therapeutic
      modalities. Although it is believed that these advances have contributed to
      improved outcomes, considerable uncertainty persists regarding key areas of
      management. OBJECTIVE: To review selected controversies in the management of
      aneurysmal subarachnoid hemorrhage, with a special emphasis on endovascular vs.
      surgical techniques for securing aneurysms, the diagnosis and therapy of cerebral
      vasospasm, neuroprotection, antithrombotic and anticonvulsant agents, cerebral
      salt wasting, and myocardial dysfunction, and to suggest venues for further
      clinical investigation. DATA SOURCE: Search of MEDLINE and Cochrane databases and
      manual review of article bibliographies. DATA SYNTHESIS AND CONCLUSIONS: Many
      aspects of care in patients with aneurysmal subarachnoid hemorrhage remain highly
      controversial and warrant further resolution with hypothesis-driven clinical or
      translational research. It is anticipated that the rigorous evaluation and
      implementation of such data will provide a basis for improvements in short- and
      long-term outcomes.

PMID- 16424736
TI  - Prescribing indications based on successful clinical trials in sepsis: a
      difficult exercise.

PMID- 16424737
TI  - Recombinant activated protein C: decisions for administration.

PMID- 16424738
TI  - Endocan, a new endothelial marker in human sepsis.
AB  - OBJECTIVES: a) To evaluate in septic patients the blood levels of endocan, a
      circulating proteoglycan, which regulates leukocyte function-associated antigen
      1/intercellular adhesion molecule-1 interactions in vitro; b) to determine
      whether endocan could be used as a diagnostic and prognostic marker in sepsis in
      the intensive care unit; and c) to study kinetics of endocan secretion by
      endothelial cells in vitro after stimulation by soluble mediators involved in
      sepsis. DESIGN: Prospective observational study. SETTING: Intensive care unit of
      the University Hospitals of Lille, France, and Geneva, Switzerland. PATIENTS: All
      patients admitted to the intensive care unit over a 6-month period with clinical
      evidence of severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: In vitro, we showed a sustained endocan secretion by endothelial
      cells after stimulation by lipopolysaccharide and tumor necrosis factor-alpha.
      Circulating levels of endocan measured in 63 patients admitted to the intensive
      care unit with sepsis were significantly elevated compared with 20 healthy donors
      and seven patients with systemic inflammatory response syndrome: 2.71 +/- 4.88
      ng/mL vs. 0.77 +/- 0.44 ng/mL vs. 0.68 +/- 1.03 ng/mL (median +/- interquartile
      range, p < .001). Endocan levels were higher in patients with septic shock (6.11
      +/- 12.99 ng/mL, n = 22) than in patients with severe sepsis (1.97 +/- 7.8 ng/mL,
      n = 12) or sepsis (1.95 +/- 1.63 ng/mL, n = 29). Measurement of endocan at
      intensive care unit admission revealed higher levels in nonsurvivors (n = 12)
      than in patients still alive 10 days later (n = 51, 6.98 +/- 13.8 vs. 2.45 +/-
      4.09, p < .01). CONCLUSIONS: These results suggest that in septic patients,
      endocan blood level is related to the severity of illness and the outcome of the
      patient and may represent a novel endothelial cell dysfunction marker.

PMID- 16424739
TI  - Antithrombotic therapies for sepsis: a need for more studies.

PMID- 16424740
TI  - Are vasopressin levels increased or decreased in septic shock?

PMID- 16424741
TI  - Tidal volumes used in acute lung injury: why the persistent gap between intended
      and actual clinical behavior?

PMID- 16424742
TI  - The role of inducible nitric oxide synthase in the evolution of myocardial
      (dys)function during resuscitated septic shock: the missing loop.

PMID- 16424743
TI  - Optimizing ventilatory support of the potential organ donor during evolving brain
      death: Maximizing lung availability for transplantation.

PMID- 16424744
TI  - Antibiotic cycling in intensive care units: the value of organized chaos?

PMID- 16424745
TI  - Severity of illness scoring in fulminant hepatic failure.

PMID- 16424746
TI  - SOAP and sepsis--analyzing what comes out in the wash.

PMID- 16424747
TI  - Standby...cardiac arrest...standby...cardiac arrest.

PMID- 16424748
TI  - Intensive care unit sedation: waking up clinicians to the gap between research
      and practice.

PMID- 16424749
TI  - How does your garden grow? The fertile fields of accountability in practice.

PMID- 16424750
TI  - Backrest elevation for the prevention of ventilator-associated pneumonia: back to
      the real world?

PMID- 16424751
TI  - Unlocking (perhaps unblocking) the microcirculation in sepsis.

PMID- 16424753
TI  - Can ventilator mode reduce ventilator-induced lung injury?

PMID- 16424752
TI  - Vasopressin: multitalented hormone among the shock hormones?

PMID- 16424754
TI  - Is impaired capillary perfusion a marker of tissue hypoxia and a hallmark of
      incipient circulatory shock?

PMID- 16424755
TI  - Toll: another piece to the puzzle of understanding neutrophil migration
      impairment in polymicrobial sepsis.

PMID- 16424756
TI  - More antioxidants in sepsis: still paved with uncertainties.

PMID- 16424757
TI  - Ten things we hate about subarachnoid hemorrhage (or, the taming of the
      aneurysm).

PMID- 16424760
TI  - Is it over yet? Time for reassessment of the determination of septic shock
      resolution.

PMID- 16424758
TI  - Endocan or endothelial cell-specific molecule-1: a novel prognostic marker of
      sepsis?

PMID- 16424761
TI  - Fluid management in acute lung injury--keep the lung dry.

PMID- 16424763
TI  - Internal medicine resident education.

PMID- 16424765
TI  - Serious errors in intensive care.

PMID- 16424767
TI  - Albumin.

PMID- 16424768
TI  - Revisiting vasopressor therapy during the first 24 hours after cardiac surgery.

PMID- 16424770
TI  - Predicting mortality.

PMID- 16424773
TI  - Acute renal failure.

PMID- 16424774
TI  - Corticosteroids after traumatic brain injury: new evidence to support their use.

PMID- 16424775
TI  - Fluconazole prophylaxis.

PMID- 16424779
TI  - Sodium nitroprusside protects adult rat cardiac myocytes from cellular injury
      induced by simulated ischemia: role for a non-cGMP-dependent mechanism of nitric
      oxide protection.
AB  - The cardioprotective actions of nitric oxide (NO) have largely been attributed to
      cGMP. NO may, however, elicit some biological actions independently of cGMP. We
      tested the hypothesis that the NO donor sodium nitroprusside specifically
      protects isolated cardiomyocytes from injury at least in part independently of
      its ability to elevate cGMP by using metabolic inhibition to simulate ischemia.
      Metabolic inhibition-induced injury of adult rat cardiomyocytes (increased
      activity of lactate dehydrogenase and creatine kinase) was significantly reduced
      by sodium nitroprusside by at least 30% at all concentrations studied (0.3-100
      microM). Sodium nitroprusside (1 microM) increased cardiomyocyte cGMP content,
      but neither a stable analogue of cGMP (8-bromo-cGMP) nor a potent cGMP stimulus
      (atrial natriuretic peptide) mimicked the protective effects of sodium
      nitroprusside. Moreover, inhibition of soluble guanylyl cyclase failed to inhibit
      sodium nitroprusside cardiomyocyte protection. Conversely, inhibition of either
      ATP-sensitive potassium (K(ATP)) channels with glibenclamide (10 microM) or
      calcium-sensitive potassium (K(Ca)) channels with tetraethylammonium bromide (1
      mM) or iberiotoxin (20 nM) markedly attenuated the cardioprotective actions of
      sodium nitroprusside. In conclusion, sodium nitroprusside protects isolated
      cardiomyocytes from metabolic inhibition independently of cGMP; rather,
      inhibition of K(Ca) and K(ATP) channels reverses the sodium nitroprusside
      actions, thus unmasking another mechanism for NO-mediated protection in
      cardiomyocytes.

PMID- 16424780
TI  - C-phycocyanin ameliorates doxorubicin-induced oxidative stress and apoptosis in
      adult rat cardiomyocytes.
AB  - Doxorubicin (DOX), a potent antineoplastic agent, poses limitations for its
      therapeutic use due to the associated risk of developing cardiomyopathy and
      congestive heart failure. The cardiotoxicity of doxorubicin is associated with
      oxidative stress and apoptosis. We have recently shown that Spirulina, a blue
      green alga with potent antioxidant properties, offered significant protection
      against doxorubicin-induced cardiotoxicity in mice. The aim of the present study
      was to establish the possible protective role of C-phycocyanin, one of the active
      ingredients of Spirulina, against doxorubicin-induced oxidative stress and
      apoptosis. The study was carried out using cardiomyocytes isolated from adult rat
      hearts. Doxorubicin significantly enhanced the formation of reactive oxygen
      species (ROS) in cells as measured by the 2',7'-dichlorodihydrofluorescein
      diacetate and dihydroethidium fluorescence. The doxorubicin-induced reactive
      oxygen species formation was significantly attenuated in cells pretreated with C
      phycocyanin. It was further observed that the doxorubicin-induced DNA
      fragmentation and apoptosis, as assayed by TUNEL assay and flow cytometry coupled
      with BrdU-FITC/propidium iodide staining, were markedly attenuated by C
      phycocyanin. C-phycocyanin also significantly attenuated the doxorubicin-induced
      increase in the expression of Bax protein, release of cytochrome c, and increase
      in the activity of caspase-3 in cells. In summary, C-phycocyanin ameliorated
      doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes. This study
      further supports the crucial role of the antioxidant nature of C-phycocyanin in
      its cardioprotection against doxorubicin-induced oxidative stress and apoptosis.

PMID- 16424781
TI  - Block of HERG channels by berberine: mechanisms of voltage- and state-dependence
      probed with site-directed mutant channels.
AB  - Berberine prolongs the duration of cardiac action potentials without affecting
      resting membrane potential or action potential amplitude. Controversy exists
      regarding whether berberine exerts this action by preferential block of different
      components of the delayed rectifying potassium current, I(Kr) and I(Ks). Here we
      have studied the effects of berberine on hERG (I(Kr)) and KCNQ1/KCNE1 (I(Ks))
      channels expressed in HEK-293 cells and Xenopus oocytes. In HEK-293 cells, the
      IC50 for berberine was 3.1 +/- 0.5 microM on hERG compared with 11 +/- 4%
      decreases on KCNQ1/KCNE1 channels by 100 microM berberine. Likewise in oocytes,
      hERG channels were more sensitive to block by berberine (IC50 = 80 +/- 5 microM)
      compared with KCNQ1/KCNE1 channels (approximately 20% block at 300 microM). hERG
      block was markedly increased by membrane depolarization. Mutation to Ala of Y652
      or F656 located on the S6 domain, or V625 located at the base of the pore helix
      of hERG decreased sensitivity to block by berberine. An inactivation-deficient
      mutant hERG channel (G628C/S631C) was also blocked by berberine. Together these
      findings indicate that berberine preferentially blocks the open state of hERG
      channels by interacting with specific residues that were previously reported to
      be important for binding of more potent antagonists.

PMID- 16424782
TI  - Simvastatin reduces serum level of vascular endothelial growth factor in
      hypercholesterolemic patients.
AB  - Vascular endothelial growth factor plays a pivotal role in the progression of
      atherosclerotic lesions and causes instability of atherosclerotic plaques by
      inducing neoangiogenesis inside the current plaque. The pro-inflammatory cytokine
      interleukin (IL-) 6 induces vascular endothelial growth factor in smooth muscle
      cells (SMC). HMG-CoA reductase inhibitors (statins), display beside their lipid
      lowering potency various pleiotropic effects. Such pleiotropic effects include
      improvement of endothelial dysfunction, increased nitric oxide bioavailability,
      antioxidant properties, inhibition of inflammatory responses, and stabilization
      of atherosclerotic plaques. In this study we investigate the influence of statin
      treatment on the serum levels of VEGF in hypercholesterolemic patients. One
      hundred and seven hypercholesterolemic patients were treated with 20 (n = 52) or
      40 mg (n = 55) simvastatin daily. Six weeks of treatment resulted in a
      significant decrease of VEGF from 1017.1 +/- 297.8 pg/mL at baseline to 543.5 +/-
      317.4 pg/mL after 6 weeks (-47.7%) and to 211.8 +/- 155.3 pg/mL after 6 months (
      79.7%; all P < 0.001). IL-6 induced the expression of vascular endothelial growth
      factor in human SMC as analyzed by rt-PCR and flow cytometry. Statins decreased
      the stimulatory effect of IL-6 on mRNA and protein levels. This effect could be
      inhibited by co-incubation with mevalonate acid. This study contributes in
      understanding the pleiotropic effects of statins particularly with regard to
      their use in treatment and prevention of cardiovascular disease.

PMID- 16424783
TI  - Estrogen replacement effectively improves the accelerated intimal hyperplasia
      following balloon injury of carotid artery in the ovariectomized rats.
AB  - Present experiments were designed to investigate the effects of ovariectomy (OVX)
      and estrogen replacement (ER) on neointimal formation after balloon injury of the
      rat carotid artery. Young adult female rats were divided into 3 groups of sham
      operation (control), ovariectomy, and ovariectomy plus estrogen replacement.
      Estrogen replacement was initiated by implanting a sustained release pellet
      containing water-soluble 17beta-estradiol 1 week after the ovariectomy. Carotid
      arteries were harvested 2 weeks after the balloon injury for determinations. The
      balloon injury caused intimal hyperplasia, which was accompanied by the impaired
      endothelium-dependent relaxation and cyclic GMP production, and accumulation of
      asymmetric dimethylarginine (ADMA) as an endogenous NOS inhibitor. Bilateral
      ovariectomy accelerated the intimal hyperplasia. The acceleration was accompanied
      by the enhanced impairment of NO production, attenuated reendothelialization, and
      enhanced accumulation of ADMA. The estrogen replacement improved the accelerated
      intimal hyperplasia with concomitant improvement of the impaired NO production
      and accumulated asymmetric dimethylarginine, and facilitated
      reendothelialization. These results suggests that the enhanced impairment of NO
      production, which possibly results from the accumulated asymmetric
      dimethylarginine and lack of reendothelialization, may contribute to the
      acceleration of intimal hyperplasia by ovariectomy and that estrogen replacement
      effectively improves the intimal hyperplasia by restoring the impaired NO
      production through reducing endogenous NOS inhibitor and facilitating
      reendothelialization.

PMID- 16424784
TI  - Losartan and prevention of atrial fibrillation recurrence in hypertensive
      patients.
AB  - The aim of the study was to evaluate the effect of losartan as compared with
      amlodipine, both associated with amiodarone, in preventing the recurrence of
      atrial fibrillation (AF) in hypertensive patients with a history of recent
      paroxysmal atrial fibrillation. Two hundred and fifty mild hypertensive (SBP >
      140 mm Hg and/or DBP > 90 < 100 mm Hg) outpatients in sinus rhythm but with at
      least two ECG-documented episodes of symptomatic atrial fibrillation in the
      previous 6 months and in treatment with amiodarone were randomized to losartan or
      amlodipine and were followed up for 1 year. Clinic blood pressure (BP) and a 24
      hour ECG was evaluated every month; the patients were asked to report any episode
      of symptomatic atrial fibrillation and to perform an ECG as early as possible.
      Two hundred and thirteen patients completed the study, 107 in the losartan group
      and 106 in the amlodipine group. After 12 months the SBP/DBP mean values were
      significantly reduced by both losartan (from 151.4/95.6 to 135.5/83.7 mm Hg, P <
      0.001 versus baseline) and amlodipine (from 152.3/96.5 to 135.2/83.4 mm Hg, P <
      0.001 versus baseline), with no difference between the two treatments. At least
      one ECG-documented episode of atrial fibrillation was reported in 13% of the
      patients treated with losartan and in 39% of the patients treated with
      amlodipine. The use of losartan in combination with amiodarone seems more
      effective than amlodipine/amiodarone combination in preventing new episodes of
      atrial fibrillation in hypertensive patients with recurrent atrial fibrillation.
      This might be related to possible favorable impact of angiotensin II receptor
      blockers (ARB) on the atrial electrical and structural remodeling in this type of
      patients.

PMID- 16424785
TI  - Activation of nitric oxide modulator effect by isometric contraction in rat
      resistance arteries.
AB  - The participation of nitric oxide (NO) as a modulator of the isometric
      contraction, as well as the underlying mechanism, was investigated in rat small
      mesenteric arteries. In the presence of a functional endothelium, L-NAME and L-NA
      similarly increased the contractions induced by phenylephrine, dependently on the
      level of contraction. However, no effect was observed in the absence of a
      functional endothelium. In the presence of selective inhibitors of protein kinase
      C (PKC) and phosphatidyl-inositol 3-kinase (PI3K), calphostin-C and wortmannin,
      respectively, the effect of L-NAME was not modified. The same observation was
      done in the presence of the tyrosine kinase inhibitors, genistein and tyrphostin
      A-23. However, in the presence of a Ca2+-independent tyrosine kinase inhibitor,
      erbstatin-A, and on the presence of a non-selective kinase inhibitor,
      staurosporine, a strong reduction was observed. Our results suggest that protein
      kinases are involved in the activation of nitric oxide modulator effect on
      isometric contractions in resistance arteries.

PMID- 16424786
TI  - P-glycoprotein modulates aldosterone plasma disposition and tissue uptake.
AB  - Aldosterone plays an important role in the pathophysiology of numerous
      cardiovascular disorders including heart failure and hypertension. Because
      aldosterone's actions are primarily mediated by its interaction with an
      intracellular mineralocorticoid receptor, factors affecting the cellular uptake
      and distribution of aldosterone may be important determinants of the hormone's
      activity. P-glycoprotein (P-gp) is an ATP-binding cassette efflux transporter
      encoded by the ABCB1 (also known as MDR1) gene in humans. P-gp is expressed on
      the luminal membrane of the capillary endothelial cells of tissues that are
      targets for aldosterone, including the brain and heart, where it attenuates
      cellular uptake of substrates. Recent in vitro evidence indicates P-gp transports
      aldosterone. Therefore, in this study we tested the hypothesis that P-gp
      modulates the uptake of aldosterone into the brain and heart by comparing the
      plasma and tissue distribution of [3H]-aldosterone in wild-type and P-gp
      deficient [mdr1a/1b (-/-)] mice. Compared with wild-type mice, [3H]-aldosterone
      activity in the plasma, brain, and heart was significantly (P < 0.05) higher in
      the mdr1a/1b (-/-) animals. The area under the plasma or tissue concentration
      time curves in the mdr1a/1b (-/-) mice was 2.0, 1.6, and 1.6-fold higher in the
      brain, heart, and plasma, respectively, than in wild-type controls. Our results
      demonstrate that P-gp plays an important role in aldosterone plasma disposition
      and modestly limits its uptake into the brain. The increased exposure of the
      brain and heart to aldosterone in the absence of P-gp suggests P-gp may play a
      key role in modulating aldosterone's effects in these organs.

PMID- 16424787
TI  - Atorvastatin reduces the expression of prostaglandin E2 receptors in human
      carotid atherosclerotic plaques and monocytic cells: potential implications for
      plaque stabilization.
AB  - Prostaglandin E2 (PGE2), the product of cyclooxygenase-2 (COX-2) and
      prostaglandin E synthase-1 (mPGES-1), acts through its receptors (EPs) and
      induces matrix metalloproteinase (MMP) expression, which may favor the
      instability of atherosclerotic plaques. The effect of statins on EPs expression
      has not been previously studied. The aim of this study was to investigate the
      effect of atorvastatin (ATV, 80 mg/d, for one month) on EP expression in plaques
      and peripheral blood mononuclear cells (PBMC) of patients with carotid
      atherosclerosis. In addition, we studied the mechanisms by which statins could
      modulate EPs expression on cultured monocytic cells (THP-1) stimulated with
      proinflammatory cytokines (IL-1beta and TNF-alpha). Patients treated with
      atorvastatin showed reduced EP-1 (14 +/- 1.8% versus 26 +/- 2%; P < 0.01), EP-3
      (10 +/- 1.5% versus 26 +/- 1.5%; P < 0.05), and EP-4 expression (10 +/- 4.1%
      versus 26.6 +/- 4.9%; P < 0.05) in atherosclerotic plaques
      (immunohistochemistry), and EP-3 and EP-4 mRNA expression in PBMC (real time PCR)
      in relation to non-treated patients. In cultured monocytic cells, atorvastatin
      (10 micromol/L) reduced EP-1/-3/-4 expression, along with COX-2, mPGES-1, MMP-9,
      and PGE2 levels elicited by IL-1beta and TNF-alpha. Similar results were noted
      with aspirin (100 micromol/L), dexamethasone (1 micromol/L), and the Rho kinase
      inhibitors Y-27632 and fasudil (10 micromol/L both). The effect of atorvastatin
      was reversed by mevalonate, farnesyl pyrophosphate, and geranylgeranyl
      pyrophosphate. On the whole, we have shown that atorvastatin reduces EPs
      expression in atherosclerotic plaques and blood mononuclear cells of patients
      with carotid stenosis and in cultured monocytic cells. The inhibition of EP
      receptors could explain, at least in part, some of the mechanisms by which
      statins could modulate the COX-2/mPGES-1 proinflammatory pathway and favor plaque
      stabilization in humans.

PMID- 16424788
TI  - Crocetin attenuates atherosclerosis in hyperlipidemic rabbits through inhibition
      of LDL oxidation.
AB  - Oxidation of low-density lipoprotein plays a crucial role in the pathogenesis of
      atherosclerosis, raising the possibility of using antioxidants as an inhibitor of
      atherosclerosis. However, studies with antioxidants have led to contradictory
      results. In the present study, we investigated the effect of crocetin, a
      carotenoid with potent antioxidant activity, on experimental atherosclerosis in
      rabbits. After 8 weeks of feeding on high lipid diet, rabbits developed severe
      atherosclerotic lesions in thoracic aortas (P < 0.01), together with a
      significant elevation of plasma lipids level, thiobarbituric acid reactive
      substances (TBARS), and oxidized low-density lipoprotein (P < 0.01). In contrast,
      supplementation with crocetin markedly reduced the progression of atherosclerotic
      lesions (P < 0.01) and plasma levels of Ox-LDL and TBARS, whereas plasma lipids
      level remained unchanged. Plasma total antioxidant capacity and superoxide
      dismutase activity were obviously increased in crocetin-treated rabbits. In vitro
      studies demonstrated that supplementation with crocetin significantly increased
      the resistance of LDL to cupric ion-induced oxidation. Regression analysis
      indicated that atherosclerotic areas correlated positively with plasma level of
      Ox-LDL and the susceptibility of LDL to in vitro oxidation. These findings
      suggest that suppression of LDL oxidation by crocetin contributes, at least
      partly, to the attenuation of atherosclerosis.

PMID- 16424789
TI  - Probucol up-regulates paraoxonase 1 expression in hepatocytes of
      hypercholesterolemic rabbits.
AB  - Paraoxonase 1 (PON1), an HDL-associated enzyme, has anti-oxidative property.
      Probucol, a hydrophobic antioxidant drug, inhibits progression of atherosclerosis
      and post-angioplasty restenosis. However, the mechanism by which probucol affects
      atherosclerosis is not completely understood. Sixteen rabbits fed with high
      cholesterol diet for 8 weeks were randomly divided into two groups: (1) starch
      group (n = 8): maintained high cholesterol diet plus starch (500 mg/kg/d) for 6
      weeks; (2) probucol group (n = 8): the same cholesterol diet plus probucol (500
      mg/kg/d) for 6 weeks. Control group (n = 8) was fed with normal diet for 14
      weeks. The classic in-situ two-step perfusion of the liver with collagenase IV
      was used to isolate the parenchymal hepatocytes. The total activity of superoxide
      dismutase (SOD) and malondialdehyde (MDA) and PON1 concentrations in serum were
      measured after 0, 8, and 14 weeks of feeding. Reverse transcription polymerase
      chain reaction (RT-PCR) was used to detect the mRNA expression of PON1. Compared
      with control group, rabbits fed with high cholesterol diet showed higher levels
      of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and
      high-density lipoprotein cholesterol (HDL-C), all of which were significantly
      reduced by probucol. Probucol significantly decreased the MDA concentration but
      was ineffective on SOD activity. High cholesterol diet decreased serum PON1
      concentration and down-regulated PON1 mRNA expression in hepatocytes. Probucol
      significantly increased serum PON1 level and up-regulated the mRNA expression of
      PON1 as compared with starch group (0.65 +/- 0.06 versus 0.46 +/- 0.05, P =
      0.001). The PON1 concentration is negatively associated with MDA concentration (r
      = -0.86, P = 0.003) but not with the level of HDL-C. In conclusion, probucol
      decreased MDA concentration, and increased PON1 serum level as well as mRNA
      expression in hepatocytes, which may help us to understand its antioxidant and
      anti-atherogenic effects.

PMID- 16424790
TI  - Comparison of captopril and enalapril to study the role of the sulfhydryl-group
      in improvement of endothelial dysfunction with ACE inhibitors in high dieted
      methionine mice.
AB  - To examine the role of sulfhydryl (-SH) group in improvement of endothelial
      dysfunction with angiotensin-converting enzyme (ACE) inhibitors in experimental
      high dose of methionine dieted rats. We compared the effects of Captopril (an ACE
      inhibitor with -SH group), enalapril (an ACE-inhibitor without -SH group), N
      acetylcysteine (only -SH group not ACE inhibitor) on endothelial dysfunction
      injured by methionine-induced hyperhomocysteinemia (HHcy) in rats. Male Sprague
      Dawley rats were divided randomly into seven groups: control group, L-methionine
      group, low dose Captopril (15 mg/kg), middle dose Captopril (30 mg/kg), high dose
      Captopril (45 mg/kg), enalapril (20 mg/kg), N-acetylcysteine (200 mg/kg); control
      group were intragastric gavaged by water and others groups were intragastric
      gavaged by L-methionine and drugs in water one time every day. Acetylcholine
      (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)
      induced endothelium-independent relaxation of aortic rings were examined.
      Paraoxonase1 (PON1) and ACE activity, malondialdehyde (MDA), nitric oxide (NO),
      superoxide dismutase (SOD) in serum were analyzed. It was found that a single
      intragastric gavage by L-methionine resulted in inhibition of endothelium
      dependent relaxation, markedly increased the serum level of malondialdehyde and
      decreased the activity of PON1 and SOD, similarly decreased the level of NO in
      the serum; but had no effects on endothelium-independent relaxation and
      angiotensin-converting enzyme activity compared with the control group. Given the
      treatment with three doses of Captopril (15 approximately 45 mg/kg) markedly
      attenuated inhibition of vasodilator responses to ACh, and eliminated the
      increased level of malondialdehyde, the decreased level of NO, activity of PON1
      and SOD in serum by single intragastric gavaged L-methionine. However, there were
      some significant differences among Captopril (30 mg/kg or 45 mg/kg), enalapril
      (20 mg/kg), and N-acetylcysteine particular in the activity of PON1 and ACE.
      These results suggested that Captopril can protect the vascular endothelium
      against the damages induced by L-methionine in rats, and the beneficial effects
      of Captopril may be related to attenuating the decrease in PON1 activity and NO
      levels. Furthermore, this protective effect may be concerned with the sulfhydryl
      group.

PMID- 16424791
TI  - Anti-atherosclerotic effect of amlodipine, alone and in combination with
      atorvastatin, in APOE*3-Leiden/hCRP transgenic mice.
AB  - We investigated the pleiotropic effects of a calcium antagonist (amlodipine) on
      early atherosclerosis development in the presence and absence of an HMG-CoA
      reductase inhibitor (atorvastatin) in apolipoprotein E*3-Leiden/human C-reactive
      protein (E3L/CRP) transgenic mice. Male E3L/CRP transgenic mice were fed a
      cholesterol-containing diet either with or without amlodipine and/or
      atorvastatin. After 31 weeks, atherosclerosis in the aortic root area was
      quantified. Treatment with amlodipine did not significantly lower blood pressure,
      but resulted in a 43% reduction (P < 0.03) of lesion area as compared with the
      untreated group. Treatment with atorvastatin resulted in an 80% reduction of
      lesion area as compared with the untreated group (P < 0.001). Combined treatment
      with amlodipine and atorvastatin decreased the lesion area by 93%, significantly
      more than either treatment alone (P < 0.008). Plasma C-reactive protein levels
      were mildly elevated, on average 10 +/- 6 mg/L, and did not differ between
      groups, neither on baseline nor during treatment. Treatment with amlodipine,
      independently of blood pressure lowering, reduced atherosclerosis development in
      E3L/CRP mice. Atorvastatin had a strong anti-atherosclerotic effect, whereas co
      treatment with amlodipine enhanced this effect significantly. Plasma C-reactive
      protein levels were not affected by any of the three treatments.

PMID- 16424792
TI  - Ketanserin, a 5-HT2 antagonist, directly inhibits the ATP-sensitive potassium
      channel in mouse ventricular myocytes.
AB  - The effects of ketanserin, a 5-HT2 antagonist, on the ATP-sensitive K+ (K(ATP))
      channels were studied in mouse ventricular myocytes using patch clamp technique.
      Under the whole-cell voltage clamp conditions, ketanserin (1-100 microM)
      reversibly inhibited pinacidil-induced K(ATP) current in a concentration
      dependent fashion with a Ki value of 9.36 microM and the Hill coefficient was
      0.67. This inhibition was developed even with the presence of 5-hydroxytryptamine
      (100 microM) in the bath. Prazosin, a selective alpha1-antagonist, also failed to
      mimic the effect of ketanserin. Ketanserin did not affect the channel activity in
      inside-out configuration under the ATP-free internal solution. Furthermore,
      ketanserin applied to the external solution did not affect the pinacidil-induced
      channel activity in the cell-attached patches, but did inhibit it when applied
      into the pipette. These results suggest that the inhibitory action of ketanserin
      observed in this study was probably due to a direct action on the K(ATP) channel
      rather than to an action through the 5-HT2 receptor or alpha1-adrenoceptor
      blockade, and that the antiarrhythmic activity of ketanserin against cardiac
      arrhythmias induced in the ischemic/reperfused heart is at least in part
      attributable to its inhibition of the K(ATP) channel.

PMID- 16424793
TI  - Effect of nucleoside transport blockade on the interstitial adenosine level
      characterized by a novel method in guinea pig atria.
AB  - Several accepted methods are available to estimate the adenosine (Ado)
      concentration of interstitial fluid ([Ado]ISF) in functioning heart, providing
      results spanning over nano- to micromolar concentrations. This extremely large
      range points to the necessity of novel approaches for estimating [Ado]ISF or at
      least the alteration from basal [Ado]ISF. In the present study, the change in
      [Ado]ISF was characterized following nucleoside transport (NT) blockade elicited
      by 10 micromol/L dipyridamole or 10 micromol/L nitrobenzylthioinosine in isolated
      guinea pig atria, by means of our novel procedure referred to as receptorial
      responsiveness method (RRM). The RRM provided an index of the change in [Ado]ISF
      under NT blockade, namely the concentration of N-cyclopentyladenosine (CPA; a
      relatively stable A1 Ado receptor agonist), which is equieffective with the
      change in [Ado]ISF regarding the contractility. Our results show that
      dipyridamole or nitrobenzylthioinosine produced an elevation in [Ado]ISF at the
      cardiomyocyte A1 Ado receptors equivalent to about 16 or 20 nmol/l CPA,
      respectively. In addition, nitrobenzylthioinosine was found more appropriate for
      selective NT blockade than dipyridamole.

PMID- 16424794
TI  - Effects of corticotropin-releasing hormone (CRH) on monocyte function, mediated
      by CRH-receptor subtype R1 and R2: a potential link between mood disorders and
      endothelial dysfunction?
AB  - Psychosocial factors have been reported to be independently associated with
      coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the
      major hormone activated during adaptive responses to stressful stimuli, the
      undergoing pathophysiological mechanism related to stress-induced endothelial
      dysfunction is still poorly understood. This study sought to investigate the
      effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we
      elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide
      (NO) release and the receptors involved. Cell adhesion was determined using an
      adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were
      quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed
      by mRNA. Corticotropin-releasing hormone induced a significant time- and
      concentration-dependent increase of cell adhesion as well as monocytic MAC-1
      expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In
      addition, corticotropin-releasing hormone significantly increased monocytic ET-1
      release whereas nitric oxide release was decreased. The effect was abolished by
      the selective CRH-receptor antagonist astressin. Our findings support the
      importance of peripherally circulating corticotropin-releasing hormones, by
      influencing specific homeostatic properties of monocytes. Our data may provide a
      novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)
      related endothelial dysfunction up to cardiovascular complications.

PMID- 16424795
TI  - Lercanidipine reduces matrix metalloproteinase-9 activity in patients with
      hypertension.
AB  - Increased levels of metalloproteinase (MMP)-9 have been shown in hypertensive
      patients. Lercanidipine is a calcium channel blocker with antioxidant actions. We
      examined whether lercanidipine produces antioxidant effects and reduces MMP-9
      activity in hypertensive patients in a placebo-controlled, crossover, single
      blinded design study including 18 healthy volunteers (control group), and 14
      hypertensive patients without (N = 7) or with (N = 7) diabetes mellitus.
      Hypertensive patients were randomized to treatment with placebo (15 days) or
      lercanidipine 20 mg/d (15 days). Arterial blood pressure was evaluated with
      ambulatory blood pressure monitoring. Plasma thiobarbituric acid reactive species
      (TBA-RS) levels were measured to assess oxidative stress, and plasma MMP-2 and
      MMP-9 were assayed by gel zymography before and after treatment with placebo or
      lercanidipine. Plasma concentrations of tissue inhibitor of metalloproteinases
      (TIMP)-1 were measured by ELISA. Lercanidipine reduced mean arterial pressure by
      7% in hypertensive patients without diabetes (P < 0.05), but not in hypertensive
      patients with diabetes. It significantly decreased plasma TBA-RS levels in
      hypertensive patients without and with diabetes (95% confidence interval [CI], 
      26 to -46%, P = 0.048, and -22 to -33%, P = 0.036, respectively). In addition,
      lercanidipine decreased activated MMP-9 in hypertensive patients without and with
      diabetes (95% CI, -19 to -47%, P = 0.047, and -80 to -96%, P = 0.010,
      respectively). No effects were seen on MMP-2. No significant differences or
      changes in plasma TIMP-1 concentrations were found. Therefore, we demonstrate for
      the first time that lercanidipine consistently decreased MMP-9 activity and
      reduced oxidative stress in hypertensive patients, thus suggesting a mechanism
      probably involved in the pleotropic actions of lercanidipine.

PMID- 16424796
TI  - Characterization of the in vivo and in vitro electrophysiological effects of the
      novel antiarrhythmic agent AZD7009 in atrial and ventricular tissue of the dog.
AB  - This study evaluated the effects of the novel antiarrhythmic agent AZD7009 on
      atrial and ventricular repolarization and on the Na+-current system, using Vmax
      as an index. Anesthetized dogs were infused with AZD7009 or azimilide to produce
      three pseudo steady-state plasma concentrations in vivo. Microelectrode
      techniques were used to record action potentials and effective refractory period
      (ERP) in vitro. Whereas AZD7009 concentration-dependently increased atrial ERP
      (AERP, by 48 +/- 7 milliseconds maximum, P < 0.001 versus vehicle), the increases
      in ventricular ERP (VERP, 8 +/- 4 milliseconds) and QT interval (2 +/- 5.5
      milliseconds) were small and not concentration-dependent. For azimilide, the AERP
      increase was less, whereas VERP and QT increases were substantially larger than
      with AZD7009. In vitro, AZD7009 concentration-dependently reduced Vmax and
      increased action potential duration (APD). ERP was increased through APD
      lengthening and post-repolarization refractoriness. The suppression of Vmax, but
      not APD prolongation, showed frequency-dependence. APD and ERP increases were
      more pronounced in atrial than ventricular tissue: in atria, 2 microM AZD7009
      increased APD90 and ERP from 224 +/- 7 to 318 +/- 7 milliseconds and 241 +/- 7
      milliseconds to 378 +/- 17 milliseconds; versus 257 +/- 5 to 283 +/- 7
      milliseconds and 253 +/- 12 to 300 +/- 11 milliseconds respectively in
      ventricles. Thus, AZD7009 potently and predominantly increases atrial
      refractoriness in the dog, with actions mediated by combined effects on
      repolarization and the Na+-current system.

PMID- 16424797
TI  - Inhibitory effect of efonidipine on aldosterone synthesis and secretion in human
      adrenocarcinoma (H295R) cells.
AB  - Targeting aldosterone synthesis and/or release represents a potentially useful
      approach to the prevention of cardiovascular disease. Aldosterone production is
      stimulated by angiotensin II (Ang II) or extracellular K+ and is mediated mainly
      by Ca2+ influx into adrenal glomerulosa cells through T-type calcium channels. We
      therefore examined the effects of efonidipine, a dual T-type/L-type Ca2+ channel
      blocker, on aldosterone secretion in the H295R human adrenocarcinoma cell line;
      100 nmol/L Ang II and 10 mmol/L K+ respectively increased aldosterone secretion
      from H295R cells 12-fold and 9-fold over baseline. Efonidipine dose-dependently
      inhibited both Ang II- and K+-induced aldosterone secretion, and nifedipine, an L
      type Ca2+ channel blocker, and mibefradil, a relatively selective T-type channel
      blocker, similarly inhibited Ang II- and K+-induced aldosterone secretion, but
      were much less potent than efonidipine. Efonidipine also lowered cortisol
      secretion most potently among these drugs. Notably, efonidipine and mibefradil
      also significantly suppressed Ang II- and K+-induced mRNA expression of 11-beta
      hydroxylase and aldosterone synthase, which catalyze the final two steps in the
      aldosterone synthesis, whereas nifedipine reduced only K+-induced enzyme
      expression. These findings suggest that efonidipine acts via T-type Ca2+ channel
      blockade to significantly reduce aldosterone secretion, and that this effect is
      mediated, at least in part, by suppression of 11-beta-hydroxylase and aldosterone
      synthase expression.

PMID- 16424798
TI  - Pharmacological evidence for calcium channel inhibition by danshen (Salvia
      miltiorrhiza) on rat isolated femoral artery.
AB  - This study investigated the relaxant actions of danshen (Salvia miltiorrhiza) and
      its lipid-soluble- and water-soluble-fractions on endothelium-denuded rat
      isolated femoral artery rings. Danshen, its water-soluble fraction and its lipid
      soluble fraction produced relaxation of the phenylephrine-precontracted artery
      rings with IC50 values of 149 +/- 20 microg/mL, 160 +/- 25 microg/mL, and 23 +/-
      6 microg/mL, respectively. Pretreatment of the artery rings with a non-selective
      potassium channel inhibitor tetraethylammonium (TEA, 10 mM) produced a
      significant two-fold rightward shift of the concentration-response curve to
      danshen and a four-fold shift to its water-soluble fraction, but had no effect on
      the lipid-soluble fraction. A 3.3-fold shift was produced on the concentration
      response curve of danshen when the artery rings were pretreated with a mixture of
      10 mM TEA, 1 mM 4-aminopyridine (K(V) blocker), 1 microM glibenclamide (K(ATP)
      blocker), 100 nM iberiotoxin (BK(Ca) blocker), and 100 microM barium chloride
      (K(IR) blocker). Involvement of Ca2+ channels was investigated in endothelium
      denuded artery rings incubated with Ca2+-free buffer and primed with 1 microM
      phenylephrine or 60 mM KCl for 5 minutes prior to adding CaCl2 to elicit
      contraction. In artery rings primed with phenylephrine, pretreatment with 1 mg/mL
      danshen, 1 mg/mL water-soluble fraction of danshen, 0.1 mg/mL lipid-soluble
      fraction of danshen, and 100 nM nifedipine abrogated the CaCl2-induced
      contraction. On the other hand, in artery rings primed with KCl, these agents
      produced 40%, 25%, 53%, and 92% inhibition on the maximum contraction induced by
      CaCl2, respectively. Increasing the concentrations of danshen and its water
      soluble fraction to 3 mg/mL, and the lipid-soluble fraction to 0.3 mg/mL further
      reduced the maximum contraction to 92%, 93%, and 83%, respectively. Taken
      together, these findings suggested the vasorelaxant actions of danshen and its
      fractions were produced primarily by inhibition of Ca2+ influx in the vascular
      smooth muscle cells and a small component was mediated by the opening of K+
      channels.

PMID- 16424799
TI  - Exogenous basic fibroblast growth factor increases collateral blood flow in
      female rats with femoral artery occlusion.
AB  - The goal of this study was to determine if extended duration of FGF-2 infusion
      would further expand collateral blood flow (BF) in female rats with bilateral
      femoral artery occlusion; rats were infused with either FGF-2 or placebo intra
      arterially for 14, 28, and 42 days. Blood flows were measured with isotope
      labeled microspheres. Blood pressure and heart rate were similar between the
      treatment groups by ANOVA. In Placebo groups; baseline collateral dependent blood
      flows to the calf muscle were 11 mL/min/100 g to 17 mL/min/100 g at 4 hours after
      femoral artery occlusion, calf muscle blood flow increased to 39 +/- 4.2, 49 +/-
      4.2, and 48 +/- 3.3 mL/min/100 g following 16, 30, and 44 days femoral artery
      occlusion respectively. In FGF-2-treated groups, calf muscle blood flows were
      further increased by 36%, 57%, and 35% over the corresponding time point of
      Placebo groups (P < 0.001). Exogenous FGF-2 infusion for 28 days showed higher
      collateral dependent blood flows than the FGF-2 14 days infused group (P <
      0.001). Extended duration of exogenous FGF-2 delivery up to 42 days failed to
      further expand the collateral blood flow. This implies a self-limiting mechanism
      that might govern the collateral vascular remodeling induced by FGF-2. Our
      results indicate that female rats can obtain similar extent collateral blood flow
      expansion as that found in the male rats.

PMID- 16424800
TI  - Effect of sex on the cardiovascular response to adrenaline in humans.
AB  - Cardiovascular responsiveness to stress conditions differs between men and women.
      It is not known to what extent this observation is explained by differences in
      the release of stress hormones like adrenaline, or by differences in the response
      to adrenaline. Therefore, we quantified the hemodynamic response to infusion of
      adrenaline (0.04, 0.06, and 0.08 microg x kg(-1) x min(-1) for 20 minutes each)
      in 8 healthy men and 8 healthy premenopausal women. Arterial plasma adrenaline
      levels were measured before and after infusion. Heart rate and intra-arterial
      blood pressure were monitored throughout the experiment. Arterial plasma
      adrenaline levels increased similarly in both sexes. There was a larger increase
      in systolic blood pressure in women compared with men (17.6 +/- 2.8 versus 5.1 +/
      3.1 mm Hg, P < 0.01). In contrast, men showed a larger increase in heart rate
      compared with women (20.3 +/- 1.4 versus 11.2 +/- 2.8 bpm, P < 0.01). In
      conclusion, these data suggest that the cardiovascular response to adrenaline is
      predominantly alpha-adrenergic in premenopausal women, and predominantly beta
      adrenergic in age-matched men.

PMID- 16424801
TI  - Ceramide attenuates hypoxic cell death via reactive oxygen species signaling.
AB  - We have previously demonstrated that tumor necrosis factor alpha (TNFalpha), a
      cytokine known to be induced by ischemia, independently promotes preconditioning
      in part via ceramide generation. As reactive oxygen species (ROS) signaling is
      evoked by ischemic preconditioning, by TNFalpha and by ceramide we reasoned that
      ceramide-induced preconditioning is ROS-mediated. Fibroblastic L-cells were
      subjected to 8 hours simulated ischemia and were preconditioned by pretreatment
      with cell permeable c2 ceramide (1 microM) with or without the antioxidant N
      mercaptopropionyl glycine (MPG; 1 mM). Pretreatment with ceramide reduced lactate
      dehydrogenase release at the end of the simulated ischemia but this
      cytoprotective effect was lost in the presence of MPG. Concurrent temporal ROS
      generation was measured using confocal microscopy on cells stained with
      dichlorofluorescein diacetate (DCF-DA). Ceramide increased ROS production after
      30 minutes and this induction was decreased by MPG. Incubation of ceramide with
      cyclooxygenase-2 inhibitor, NS 398 (10 microM), or with a mitochondrial
      respiratory chain inhibitor, rotenone (10 microM) reduced the cytoprotective
      effect of ceramide in parallel with a partial diminution in ROS generation. In
      contrast, inhibition of other ROS-producing systems including nitric oxide
      synthase, xanthine oxidase, or NADPH oxidase failed to modulate ceramide-induced
      cytoprotection. Collectively, these data demonstrate that ceramide induces a cell
      survival program through ROS signaling activated, in part, via cyclooxygenase and
      the mitochondrial respiratory chain.

PMID- 16424802
TI  - Chronic posttraumatic anterior dislocation of the radial head in children:
      thirteen cases treated by open reduction, ulnar osteotomy, and annular ligament
      reconstruction through a Boyd incision.
AB  - OBJECTIVE: To report the results of open reduction, ulnar osteotomy, and annular
      ligament reconstruction all through a Boyd incision for chronic radial head
      dislocations in children. DESIGN: Retrospective review. SETTING: Tertiary
      pediatric orthopaedic care unit at a general hospital in Taichung, Taiwan.
      PATIENTS/PARTICIPANTS: From 1986 to 2003, 13 children, aged 4 to 13 (mean, 8.3)
      years, who had a chronic traumatic anterior dislocation of the radial head were
      treated at our institute. These patients were seen at our hospital 2 to 36 (mean,
      8.2) months after injury. INTERVENTION: Open reduction of the radial head, ulnar
      osteotomy, then rigid fixation with plate/screws, and annular ligament
      reconstruction with forearm fascia, all performed through a Boyd incision. MAIN
      OUTCOME MEASUREMENTS: Forearm radiographs for reduction and osteotomy site union,
      physical examinations for elbow mobility, and Kim's elbow performance scores for
      overall elbow function. Evaluations were done at a special follow-up clinic for
      this study by a pediatric orthopaedic surgeon who was not involved in the
      patients' previous care. RESULTS: Patient follow-up averaged 7.8 (range, 1-16.9)
      years after surgery. Twelve of our cases had successful radial head reductions,
      satisfactory elbow mobility, and excellent functional outcome. One case had a
      redislocation, was retreated, and had a fair result. Other complications included
      1 patient with transient posterior interosseous nerve palsy, and 1 delayed union
      of an ulnar osteotomy site, which healed without further intervention at 1 year
      with an excellent result. CONCLUSION: This surgical procedure provides a high
      success rate with a low level of complications for chronic radial head
      dislocations in children.

PMID- 16424803
TI  - Is the absence of an ipsilateral fibular fracture predictive of increased
      radiographic tibial pilon fracture severity?
AB  - OBJECTIVE: Despite their frequent occurrence, there is little clinical or
      biomechanical data associating the status of the fibula with any injury pattern
      of the tibial plafond. Similarly, the integrity of the fibula is not assessed in
      the commonly used tibial pilon fracture classification schemes. The purpose of
      this study was to determine whether there is a difference in the radiographic
      severity of tibial pilon injuries with fibular fractures compared with those
      without fibular fractures by using a rank-order method. DESIGN: Case-control,
      radiographic review. SETTING: Urban level-1, university trauma center. PATIENTS:
      During a 36-month period, 20 consecutive tibial pilon injuries without associated
      fibular fractures were retrospectively identified by using a prospectively
      gathered trauma database (group 1). During the same time period, an additional
      197 tibial pilon injuries with fibula fractures were identified and classified
      according to the AO/OTA System. This included 48 AO/OTA 43B-type (24.4%) and 149
      AO/OTA 43C-type (75.6%) fractures. From this larger group of patients, an age-
      (+/-5 years) and gender- matched cohort of 20 tibial pilon injuries with fibular
      fractures were randomly selected electronically (group 2). INTERVENTION: Digital
      concealment of the fibula on the anteroposterior and lateral injury radiographs.
      MAIN OUTCOME MEASURE: Before definitive fixation, 3 orthopaedic traumatologists
      independently ranked the digitized anteroposterior and lateral radiographs of all
      40 patients according to severity with 40 representing the most severe injury.
      RESULTS: Interobserver agreement between the 3 evaluators showed a significant
      positive association (Kendall's concordance coefficient = 0.87; P = 0.0001). The
      overall mean rank score for tibial pilon injuries with fibula fractures was 24.4,
      whereas those without fibula fractures was 16.7 (t test = 0.02). When evaluated
      within the AO/OTA classification system, the mean rank score for C-type tibial
      pilon fracture patterns was 10.3 in group 1 and 8.7 in group 2 (P = 0.5). AO/OTA
      C-type tibial pilon fracture patterns were observed more commonly in group 2 than
      in group 1 (P = 0.006). CONCLUSIONS: This study demonstrates that, overall,
      tibial pilon injuries with fibular fractures were statistically ranked as more
      radiographically severe than those without fibular fractures. Fibular fractures
      are more commonly associated with C-type injuries than B-type injuries. There was
      no difference in severity in C-type injuries with or without fibular fractures;
      however, C-type injuries were ranked, as a group, significantly more
      radiographically severe than B-type injuries.

PMID- 16424804
TI  - Stress radiographs after ankle fracture: the effect of ankle position and deltoid
      ligament status on medial clear space measurements.
AB  - OBJECTIVE: This study was designed to determine 1) how ankle position affects the
      medial clear space by using stress radiographs, 2) which medial clear space
      measurement, overall width or increase in width, better predicts deep deltoid
      ligament disruption after Weber type-B distal fibular fracture, and 3) what value
      of medial clear space is most predictive of deep deltoid ligament disruption
      after Weber type-B distal fibular fracture. DESIGN: Cadaveric fracture model.
      SETTING: Biomechanics laboratory. INTERVENTION: Fluoroscopic mortise views were
      taken of 6 fresh cadaveric ankles mounted in a fixture permitting both
      positioning in neutral flexion, dorsiflexion, and plantarflexion, and the
      application of internal and external rotational forces. After destabilizing the
      ankles according to the supination-external rotation mechanism of Lauge-Hansen,
      repeat radiographs were taken with the same combination of flexion and applied
      rotational stress. MAIN OUTCOME MEASURE: Radiographic measurements of medial
      clear space width and changes in medial clear space were made. RESULTS: A medial
      clear space of > or =5 mm on radiographs taken in dorsiflexion with an external
      rotational stress was most predictive of deep deltoid ligament transection after
      distal fibular fracture. In dorsiflexion-external rotation, medial clear spaces
      of > or =4 mm yielded lower specificity and positive predictive value, whereas >
      or =6 mm yielded lower sensitivity and negative predictive value. All other
      stress conditions and increases in medial clear space of 2 or 3 mm were less
      predictive. CONCLUSIONS: Ankle stress radiographs taken in dorsiflexion-external
      rotation were most predictive of deep deltoid ligament disruption after distal
      fibular fracture. Under this stress condition, a medial clear space of > or =5 mm
      was the most reliable predictor of deep deltoid ligament status.

PMID- 16424805
TI  - The deltoid muscle: an anatomic description of the deltoid insertion to the
      proximal humerus.
AB  - OBJECTIVE: This study was designed to describe the anatomic insertion point of
      the deltoid to the proximal humerus. DESIGN: Gross anatomic study. SETTING: Level
      one academic trauma center. PATIENTS: Cadaveric study. MAIN OUTCOME MEASUREMENTS:
      Bilateral humeri were stripped of soft tissue except the deltoid insertion point.
      The length of the humeri was recorded. The distance from the greater tuberosity
      to the proximal most aspect of the tendinous insertion point and the distal most
      tendinous attachment was measured. The humeri were cross-sectioned 5-mm distal to
      the proximal insertion point, 5-mm proximal to the distal insertion point, and
      midway between these 2 points. The circumferential proportion of humerus into
      which the tendon inserted at each point was recorded. RESULTS: The mean length of
      the deltoid insertion was 97 (range, 83-111) mm. The mean distance from the
      greater tuberosity to the proximal insertion point was 61 (range, 55-75) mm and
      to the distal insertion was 158 (range, 142-172) mm. The deltoid occupied on
      average: 8% of the humeral circumference 5 mm from the proximal insertion point,
      39% at the mid point of the insertion, and 31% of the humeral circumference 5 mm
      from the distal insertion point. CONCLUSIONS: The deltoid insertion is long and
      broad. A 4.5-mm plate would result in detaching 13.5 mm of the insertion, leaving
      at least half of the original insertion attached to the humerus.

PMID- 16424806
TI  - Hip arthroscopy to remove loose bodies after traumatic dislocation.
AB  - OBJECTIVES: This study was designed to review the incidence of arthroscopically
      detected intra-articular loose bodies found in patients after traumatic hip
      dislocation or small acetabular wall fracture which would not otherwise be
      treated without surgery. DESIGN: Retrospective review. SETTING: Level 1 academic
      trauma center. PATIENTS: Thirty-six patients who sustained traumatic hip injuries
      and subsequently had 39 hip arthroscopies between November 1997 and January 2004
      were reviewed. INTERVENTION: All patients had standard AP pelvis x-rays and CT
      scans performed. At our institution, patients with hip dislocations or acetabular
      wall fractures not otherwise requiring surgery are routinely offered hip
      arthroscopy to remove loose bodies. The radiographs were reviewed to determine
      incidence of loose bodies or nonconcentric reduction before hip arthroscopy.
      Chart review provided incidence of loose bodies found during arthroscopy. MAIN
      OUTCOME MEASUREMENTS: Comparison was made between radiographic data obtained
      preoperatively and operative findings. RESULTS: Loose bodies were found in the
      hips of 33 of 36 patients (92%) who were arthroscoped. Loose bodies were found in
      7 of 9 cases (78%) in which standard radiographic studies (AP pelvis x-rays and
      CT scan) found no loose bodies and a concentric reduction. CONCLUSIONS: Loose
      bodies are routinely present after closed treatment of hip dislocations or wall
      fractures not otherwise requiring surgery, even when radiographs are negative.
      Hip arthroscopy may be indicated for loose body removal when open treatment is
      not otherwise necessary.

PMID- 16424807
TI  - Gene expression during fracture healing in rats comparing intramedullary fixation
      to plate fixation by DNA microarray.
AB  - OBJECTIVE: This study was designed to compare mRNA gene expression in healing
      diaphyseal femoral fractures between those injuries treated with intramedullary
      nails and those treated with internal plate fixation. DESIGN: RNA gene expression
      was measured at 1 day, 3 days, and 1, 2, 4, and 6 weeks after surgery in the
      fracture callus of rats randomized to femoral shaft fracture with intramedullary
      nail fixation, rigid plate fixation, or sham fracture. SETTING: AAALAC-accredited
      vivarium of an independent academic medical center. ANIMALS: Fifty-seven, adult,
      female, Sprague-Dawley rats at 16 weeks of age. INTERVENTION: Femoral fracture
      with intramedullary nail fixation, femoral fracture with plate and screw
      fixation, or sham surgery with no fracture. MAIN OUTCOME MEASUREMENTS: RNA
      expression for 8700 genes was measured with 19 Affymetrix U34A microarrays. The
      fracture callus was significantly larger with intramedullary nail fixation than
      with plate fixation. Most genes responded to fracture with a change in mRNA
      expression. Most of the responding genes followed the same time course for both
      fixation methods. This included genes related to growth factors, bone matrix,
      mast cells, most nerve factors, and hematopoiesis. The intramedullary nail group
      had significantly greater up-regulation for transcripts related to cartilage,
      cell division, inflammation, and the acetylcholine receptor. There was
      significantly greater up-regulation in the plate group for genes related to
      macrophage activity. CONCLUSIONS: There were differentially expressed genes
      present between the 2 surgical groups that may give insight into the control of
      fracture repair.

PMID- 16424808
TI  - External fixator parts should not be reused.

PMID- 16424809
TI  - Reuse of selected external fixator components is safe and should be supported.

PMID- 16424810
TI  - The trochanteric C-clamp for provisional pelvic stability.
AB  - The application of a pelvic clamp for provisional stability of unstable pelvic
      fractures has been advocated in the orthopaedic literature. Although the
      technique has gained some supporters, problems with placement and associated
      complications have prevented widespread acceptance. We have modified the pelvic
      clamp (ACE Pelvic Stabilizer) technique by applying the clamp to the trochanteric
      region of the femur and applying a reduction force similar to a pelvic binder or
      external fixator.

PMID- 16424811
TI  - Trans-iliac removal of bullet fragments from the sacroiliac joint.
AB  - The need for removal of intra-articular bullet fragments is well documented in
      the literature. Arthroscopy and arthrotomy are the preferred methods to access
      large superficial joints; however, these methods cannot be effectively used to
      access the sacroiliac joint. Its relationship to vital soft tissues and its
      convoluted joint anatomy make it almost impossible to explore even under open
      methods. We propose a new percutaneous technique for the removal of intra
      articular bullet fragments from the sacroiliac joint. Our method meets two
      important goals: 1) percutaneous minimally invasive approach to the joint, and 2)
      removal of the bullet fragments while avoiding the potential morbidity of an open
      procedure.

PMID- 16424812
TI  - Operative treatment of osteochondral nonunion of the distal humerus.
AB  - Three patients with ununited osteochondral fracture fragments of the distal
      humerus (2 anterior capitellum and trochlea; 1 posterior trochlea) who had
      debridement and realignment of the nonunion, autogenous cancellous bone graft,
      and internal fixation an average of 6 (range, 5-8) months after injury were
      studied. The preoperative arc of elbow flexion was 80 degrees, 35 degrees, and 25
      degrees. All 3 fractures healed without implant related complications or
      osteonecrosis. At 28, 27, and 46 months after the index procedure for nonunion,
      the patients had 95 degrees, 90 degrees, and 115 degrees arcs of elbow flexion.
      The scores on the Mayo Elbow Performance Index were 80, 80, and 95 (2 good, 1
      excellent). Based on this limited experience, it seems that operative treatment
      of ununited osteochondral fracture fragments can achieve union without
      osteonecrosis. Attempts to improve the function of the native elbow rather than
      salvage the situation with interpositional or prosthetic arthroplasty are
      worthwhile.

PMID- 16424813
TI  - Management of failed total ankle replacement with a retrograde short femoral
      nail: a case report.
AB  - Arthrodesis of the ankle joint after failed total ankle replacement using
      internal fixation with plates and screws is problematic because of the
      significant bone loss. An external fixator has the disadvantage of prolonged
      treatment until complete consolidation, frequently complicated by pin track
      infections. Recently an intramedullary fixation has been described for tibio-talo
      calcaneal arthrodesis for posttraumatic osteoarthritis of the ankle joint. We
      report on the use of this technique plus bone graft in a case of failed total
      ankle replacement complicated by cystic talus degeneration and a massive bony
      defect. The advantages include early mobilization and weightbearing provided by
      the stability of the fixation.

PMID- 16424814
TI  - Absorbable implants in surgical correction of a capitellar malunion in an 11-year
      old: a case report.
AB  - We present the case of an 11-year-old girl who had a corrective osteotomy
      reconstruction using absorbable implants for a malunited capitellar fracture 3
      1/2 months after a dislocation of her elbow joint. This operative stabilization
      enabled early joint mobilization and, finally, excellent results in terms of
      anatomy and function at a 2-year follow-up. We were not able to find any similar
      report in the English literature dealing with corrective osteotomy reconstruction
      using absorbable implant fixation for a malunited capitellum in a child.

PMID- 16424815
TI  - Distal tibia fracture: Opinion: Open reduction and internal fixation.

PMID- 16424816
TI  - Distal tibia fracture: Opinion: intramedullary nailing.

PMID- 16424817
TI  - Distal tibia fracture: Opinion: nonoperative treatment.

PMID- 16424818
TI  - Treatment of distal tibia fractures without articular involvement: a systematic
      review of 1125 fractures.
AB  - BACKGROUND: The management of unstable distal tibia fractures remains
      challenging. The mechanism of injury and the prognosis of these fractures are
      different from pilon fractures, but their proximity to the ankle makes the
      surgical treatment more complicated than the treatment tibial midshaft fractures.
      A variety of treatment methods have been suggested for these injuries, including
      nonoperative treatment, external fixation, intramedullary nailing, and plate
      fixation. However, each of these treatment options is associated with certain
      challenges. Nonoperative treatment may be complicated by loss of reduction and
      subsequent malunion. Similarly, external fixation of distal tibia fractures may
      result in insufficient reduction, malunion, and pin tract infection.
      Intramedullary nailing can be considered the "gold standard" for the treatment of
      tibial midshaft fractures, but there are concerns about their use in distal tibia
      fractures. This is because of technical difficulties with distal nail fixation,
      the risk of nail propagation into the ankle joint, and the discrepancy between
      the diaphyseal and metaphyseal diameter of the intramedullary canal. Open
      reduction and internal plate fixation results in extensive soft tissue dissection
      and may be associated with wound complications and infections. The optimal
      treatment of unstable distal tibia without articular involvement remains
      controversial. OBJECTIVES: This study was designed to review the outcomes of
      different treatment methods for extra-articular distal tibia fractures. The
      English literature was systematically reviewed and the rates of malunion,
      nonunion, infection, fixation failure, and secondary surgical procedures were
      extracted.

PMID- 16424819
TI  - A single nucleotide polymorphism in CHAT influences response to
      acetylcholinesterase inhibitors in Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a devastating neurodegeneration with a
      characteristic deficit in cholinergic neurotransmission. Treatment with
      acetylcholinesterase (AChE) inhibitors aims to reverse this deficit and does
      ameliorate the decline in cognition in some AD patients, although response is
      variable. OBJECTIVE: To examine whether sequence variation in the gene encoding
      choline acetyltransferase (CHAT), which encodes the major catalytic enzyme of the
      cholinergic pathway, predicts response to AChE inhibitors. METHODS: Alzheimer's
      disease patients (121) were treated with cholinesterase inhibitors and the effect
      of treatment on cognition was measured using the Mini Mental State Examination
      (MMSE). Six polymorphisms in CHAT were analysed for association with change in
      MMSE score. RESULTS: After correction for multiple testing, we found one SNP,
      rs733722, in a promoter region of CHAT, is associated with response of AD
      patients to cholinesterase inhibitors (P = 0.03) and accounts for 6% of the
      variance in response to AChE inhibitors. CONCLUSION: Rs733722 represents a
      putative marker of response to AChE inhibitors in AD patients.

PMID- 16424820
TI  - Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in
      cultured human hepatocytes.
AB  - UGT1A1 is induced by phenobarbital. We investigated whether three common UGT1A1
      variants are associated with the variability in UGT1A1 inducibility. Human
      hepatocytes were incubated with 2 mM phenobarbital for 2 and 6 days followed by 5
      microM SN-38 (1 h), a UGT1A1 probe. SN-38 glucuronidation in the cell media was
      measured by high-performance liquid chromatography. Three UGT1A1 promoter
      variants [-53(TA)(6>7), -3156G > A and -3279T > G] were genotyped. Significant
      induction of UGT1A1 catalytic activity was observed in 82% and 100% of the
      cultures treated with phenobarbital for 2 days (median fold-induction = 1.6,
      range 1.3-2.8; n = 28) and 6 days (median fold-induction = 2.8, range 1.6-6.4; n
      = 16), respectively. After 2 days of treatment, a negative correlation was
      observed between the UGT1A1 basal activities and the fold-induction (Spearman r =
      -0.52, P < 0.005). By contrast, the UGT1A1 activities in the basal and induced
      states were highly correlated (Spearman r = 0.95, P < 0.0001). Similar results
      were observed after 6 days of treatment. The allele frequencies were not
      significantly different between induced (n = 22) and non-induced preparations (n
      = 6) (P > 0.05). The fold-induction was not associated with any variants (P >
      0.05). The basal and induced activities were correlated with -53(TA)(6>7) (and
      with -3156G > A due to almost complete linkage with the -53 indel) (P = 0.001).
      No association was found with the -3279T > G single nucleotide polymorphism (P >
      0.05). The indel at -53 affects the basal phenotype and appears to limit the
      hepatocyte capability of maximal induction after phenobarbital. However, variants
      at -53, -3156 and -3279 are not associated with variability in UGT1A1
      inducibility.

PMID- 16424821
TI  - Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in
      workers exposed to styrene.
AB  - The present study comprised a biomonitoring study in 95 workers occupationally
      exposed to styrene and 98 unexposed controls, employing an integrated approach
      involving biomarkers of exposure, effect, and susceptibility. Airborne styrene
      was evaluated at workplace, and urinary styrene metabolites, mandelic acid (MA),
      phenylglyoxylic acid (PGA), vinylphenols (VPTs) and phenylhydroxyethylmercapturic
      acids (PHEMAs), were measured as biomarkers of internal dose. Cytogenetic
      alterations were evaluated by analysing the frequency of chromosomal aberrations
      (CAs) and micronucleated binucleated cells (MNBN) in peripheral blood
      lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in
      situ hybridization to distinguish micronuclei (MN) arising from chromosomal
      breakage (C- MN) from those harboring whole chromosomes (C+ MN). The possible
      influence of genetic polymorphisms of xenobiotic-metabolizing enzymes involved in
      styrene biotransformation (EPHX1, GSTT1, GSTM1, GSTP1) and NAT2 on the
      cytogenetic endpoints was investigated. The exposed workers showed a
      significantly higher frequency of MNBN (13.8+/-0.5% versus 9.2+/-0.4%; P<0.001)
      compared to control subjects. The effect appeared to concern both C- and C+ MN. A
      positive correlation was seen between the frequency of C+ MN and urinary level of
      MA+PGA (P<0.05) and VPTs (P<0.001). Chromosome-type CAs positively correlated
      with airborne styrene level and VPTs (P<0.05), whereas chromatid-type CAs
      correlated with PHEMAs (P<0.05). Workers bearing GSTM1 null genotype showed
      lowered levels of PHEMAs (P<0.001). The GSTT1 null genotype was associated with
      increased MNBN frequencies in the exposed workers (P<0.05) and the fast activity
      EPHX genotype with a moderate decrease in both MNBN and CAs in the controls. Our
      results suggest that occupational exposure to styrene has genotoxic effects that
      are potentiated by the GSTT1 gene deletion. These observations may have relevance
      considering the risk of lymphatic and haematopoietic malignancies tentatively
      associated with styrene exposure.

PMID- 16424822
TI  - Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter
      population differences in maintenance dose of warfarin in Japanese, Caucasians
      and African-Americans.
AB  - OBJECTIVE: To investigate pharmacokinetic and pharmacodynamic factors associated
      with population differences in warfarin doses needed to achieve anticoagulation,
      in particular the possible involvement of genetic variability in vitamin K
      epoxide reductase (VKOR) and CYP2C9. METHODS: Warfarin maintenance dose, unbound
      plasma S-warfarin concentration [Cu(S)] and INR were determined in 157
      Caucasians, 172 Japanese, and 36 African-Americans stably anticoagulated
      patients. In a subset (n = 166), fully carboxylated plasma normal prothrombin
      levels (NPT) were also measured. Genotyping for seven CYP2C9 (CYP2C9*1 through 6
      and *11) and seven VKORC1 variants were performed in 115 Caucasians and 64
      Japanese patients and 66 healthy African-Americans. Multivariate analysis was
      performed to identify covariates associated with warfarin requirement. RESULTS:
      The relationship between NPT and Cu(S) indicated Japanese are more susceptible to
      inhibition of NPT production by S-warfarin than the other two populations. VKORC1
      1173 C > T had a greater frequency in Japanese (89.1%) than Caucasians (42.2%)
      and African-Americans (8.6%). CYP2C9 variants with reduced metabolizing ability
      were less frequent in Japanese compared to the other two populations. The median
      warfarin dose was significantly higher in Caucasians than Japanese patients (5.5
      versus 3.5 mg/day), however, when matched for CYP2C9*1 homozygosity, no
      difference in dose was observed between VKORC1 genotype-matched groups.
      Furthermore, VKORC1 1173C > T and CYP2C9 (*2/*3/*11) genotypes, age and weight
      were identified as independent covariates contributing to interpatient
      variability in warfarin dosage. CONCLUSIONS: Both VKORC1 and CYP2C9 polymorphisms
      contribute to inter-population difference in warfarin doses among the three
      populations, but their contribution to intra-population variability may differ
      within each population.

PMID- 16424823
TI  - Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV.
      Role of dopaminergic pathway gene polymorphisms.
AB  - OBJECTIVE: Tardive dyskinesia (TD) is an antipsychotic induced side effect
      observed in 20-30% of schizophrenia subjects on long-term typical antipsychotic
      treatment. We tested the possible association of 24 polymorphisms from six
      dopaminergic genes: namely, dopamine receptors D1, D2, D3, D4; the dopamine
      transporter (DAT); and the catalyzing enzyme catechol-O-methyltransferase (COMT),
      with TD. METHODS: Multiple SNP/VNTR markers from candidate genes were analyzed
      using suitable approaches and allelic, genotypic and haplotypic associations were
      tested. RESULTS: 120 bp duplication marker, 1.2 kb upstream from initiation codon
      of DRD4 gene showed a significant genotypic association [chi2 = 9.29, P = 0.009;
      OR (95% CI) = 0.52 (0.31-0.86) for genotype 120 dup/120 dup]. In the COMT gene, a
      significant allelic [chi2 = 13.87, P = 0.0002] as well as genotypic association
      [chi2 = 16.08, P = 0.0003; OR (95% CI) = 0.24 (0.11-0.55) for genotype GG] was
      observed with the 408 C>G (exon 4) single nucleotide polymorphism and a
      significant genotypic association [chi2 = 6.32, P = 0.04; OR (95% CI) = 0.50
      (0.33-0.92) for genotype GG] was observed with 472 G > A (exon 4, Val 158 Met)
      SNP. 120 bp dup-T-repeat 3 in DRD4 and G-C-A-insC in COMT genes were observed to
      be TD associated haplotypes. CONCLUSIONS: Our study presents a detailed analysis
      of the possible role of dopaminergic genes in the genesis of TD. DRD4 and COMT
      genes were observed to be the most important candidates in North Indian
      schizophrenia subjects. These suggestive associations need to be investigated in
      replicate studies.

PMID- 16424824
TI  - Effect of intestinal CYP3A5 on postoperative tacrolimus trough levels in living
      donor liver transplant recipients.
AB  - It has been reported that hepatic and intestinal cytochrome P450 (CYP) 3A4,
      CYP3A5 and P-glycoprotein affect the pharmacokinetics of tacrolimus, and that
      these proteins are associated with the large inter-individual variation in the
      pharmacokinetics of this drug. We previously showed that the concentration/dose
      ratio of tacrolimus tended to be lower in recipients of living-donor liver
      transplantation (LDLT) with a CYP3A5*1/*1-carrying graft. However, the effect of
      intestinal CYP3A5 remains to be elucidated. In the present study, we examined the
      CYP3A5 genotype in both recipients and donors, and the effect of the recipients'
      polymorphism on the concentration/dose ratio of tacrolimus in patients after
      LDLT. The CYP3A5*3 allele frequency was 80% in recipients and 77% in donors. The
      intestinal CYP3A5 mRNA expression level was significantly associated with
      genotype. The tacrolimus concentration/dose ratio was lower in recipients with
      the CYP3A5*1/*1 and *1/*3 genotype (CYP3A5 expressors) compared to the
      CYP3A5*3/*3 genotype (non-expressors). Amongst the combination of CYP3A5
      genotypes between the graft liver and the native intestine, CYP3A5 expressors in
      both the graft liver and the native intestine had the lowest concentration/dose
      ratio of tacrolimus during 35 days after LDLT. Patients with the intestinal
      CYP3A5*1 genotype tended to require a higher dose of tacrolimus compared to the
      other group with the same hepatic CYP3A5 genotype. These results indicate that
      intestinal CYP3A5, as well as hepatic CYP3A5, plays an important role in the
      first-pass effect of orally administered tacrolimus.

PMID- 16424825
TI  - The absence of interaction between drug metabolizing enzyme genotypes and
      maternal lifestyle factors on glycophorin A somatic mutation frequency levels in
      newborns.
AB  - Prenatal exposure to carcinogens results in newborn DNA damage which in turn is
      associated with impaired health conditions in both childhood and adulthood. The
      present study aimed to evaluate whether phase I and II biotransformation enzyme
      genetic polymorphisms in combination with environmental exposures during
      pregnancy result in elevated levels of newborn DNA damage. Maternal peripheral
      and umbilical cord blood samples from 406 mother/newborn pairs were genotyped for
      a panel of phase I/II metabolic enzymes (CYP1A1, CYP2E1, GSTM1, GSTT1 and NAT2)
      responsible for the metabolism of tobacco and lifestyle-related mutagens and
      carcinogens. DNA damage was measured by somatic cell mutation frequency at the
      glycophorin A (GPA) locus in newborns. No association with elevated somatic cell
      mutation frequency was observed between the combination of maternal/newborn
      genotypes and cigarette smoke or lifestyle exposures. The observed variation in
      newborn GPA frequency might be due to either environmental factors not assessed
      in this study or inter-individual differences in alternative metabolic or DNA
      repair pathways.

PMID- 16424826
TI  - Screening for the alpha-adducin Gly460Trp variant in hypertensive patients: a
      cost-effectiveness analysis.
AB  - BACKGROUND: Studies have shown that approximately 80% of hypertensive patients do
      not take diuretics despite their recommendation as a first-line therapy. A recent
      study reported that hypertensive patients with the Gly460Trp variant in the alpha
      adducin gene are more likely to benefit from diuretic therapy. The objective of
      this study was to evaluate the potential cost effectiveness of screening for the
      alpha-adducin Gly460Trp variant among hypertensive patients. METHODS: A decision
      analytic Markov model was developed to estimate the clinical and economic
      outcomes comparing screening for the Gly460Trp variant to identify patients for
      addition of a diuretic compared to no screening and no addition of diuretic
      (usual care) in a hypothetical cohort of treated hypertensive patients not
      receiving diuretic therapy. We used a lifetime horizon and payer perspective.
      Cost, utility and epidemiological data were obtained from the literature. One
      way, probabilistic, and scenario sensitivity analyses were conducted to evaluate
      the uncertainty in the results. RESULTS: The screening strategy increased quality
      adjusted life years (QALYs) by 0.14 (95% confidence range [CR]: 0.05, 0.36) and
      saved dollar 1834 (dollar 505, dollar 5174) compared to usual care. The most
      influential input was the strength of the interaction between the alpha-adducin
      gene variant and diuretic effect. CONCLUSIONS: Our results suggest that screening
      for the alpha-adducin gene variant may be a useful mechanism to identify patients
      most likely to benefit from diuretic therapy and improve compliance with current
      treatment guidelines.

PMID- 16424827
TI  - In acute leukemia, the polymorphism -211C>T in the promoter region of the
      multidrug resistance-associated protein 3 (MRP3) does not determine the
      expression level of the gene.

PMID- 16424828
TI  - The goal is quantitative cerebral blood flow.

PMID- 16424830
TI  - New developments in perfusion imaging by bolus tracking.
AB  - The author describes the theoretical basis of quantification of cerebral blood
      flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) by the bolus
      tracking method: i.e.dynamic susceptibility contrast MRI using very rapid imaging
      to capture the first pass of intravenously injected paramagnetic contrast agent.

PMID- 16424829
TI  - Comparative overview of brain perfusion imaging techniques.
AB  - Numerous imaging techniques have been developed and applied to evaluate brain
      hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon
      Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT),
      Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic
      Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler
      Ultrasound. These techniques give similar information about brain hemodynamics in
      the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of
      them are used to characterize the same types of pathological conditions. However,
      each technique has its own advantages and drawbacks. This article addresses the
      main imaging techniques dedicated to brain hemodynamics. It represents a
      comparative overview, established by consensus among specialists of the various
      techniques. For clinicians, this paper should offers a clearer picture of the
      pros and cons of currently available brain perfusion imaging techniques, and
      assist them in choosing the proper method in every specific clinical setting.

PMID- 16424831
TI  - Application of regional perfusion imaging to extra-intracranial bypass surgery
      and severe stenoses.
AB  - Arterial Spin Labeling (ASL) is a non-invasive method to quantitatively measure
      perfusion without the need of contrast material. Measurement of perfusion is
      derived from the subtraction of two consecutively acquired scans, with or without
      radio frequency labeling of the magnetization in the feeding arteries. So far,
      almost all ASL methods only allowed labeling the entire feeding artery tree of
      the brain simultaneously, without separation of the individual perfusion
      territories. In this paper, we describe a newly developed method, Regional
      Perfusion Imaging, allowing quantitative measurement of perfusion in the
      watershed of individually labeled arteries (right and left internal carotids, as
      well as basilar artery and the posterior circulation). Unlike conventional
      digital subtraction angiography, this new method is completely non-invasive, and
      allows to selectively measure cerebral perfusion, and not only to get angiograms
      of the feeding vessels. Regional perfusion was already measured in more than 70
      elderly healthy volunteers and over 30 patients with internal carotid disease
      (severe stenoses and/or after extra-intracranial bypass surgery). A large
      variation among perfusion territories, even in healthy volunteers, can be
      appreciated. This method has the potential to increase our understanding of the
      relationship between collateral flow and regional perfusion in patients with
      neurovascular diseases.

PMID- 16424832
TI  - Potential applications of laser polarised xenon for CBF measurements by NMR.
AB  - Laser polarised (hyperpolarised) 129Xe offers a new potential way for assessment
      of cerebral blood flow (CBF) by nuclear magnetic resonance (NMR). We present the
      basic physical principles underlying noble gases'laser polarisation.
      Distinguishing characteristics of 129Xe NMR properties as well as theoretical
      basis for CBF measurement using laser polarised 129Xe are emphasized. Recent
      results are briefly presented and potential applications as well as current
      limitations of 129Xe in CBF studies are discussed.

PMID- 16424833
TI  - Measurement of cerebral reserve capacity using acetazolamide loading xenon CT CBF
      before carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Brain swelling and/or hemorrhage can occur after carotid
      endarterectomy. This phenomenon is called the hyperperfusion syndrome. Several
      factors contribute to this syndrome. One is reperfusion in a maximally dilated
      vessel which means disappearance of cerebral reserve capacity (CRC). The aim of
      the study was to determine whether CRC measurement was useful for intraoperative
      and postoperative management of carotid endarterectomy. PATIENTS AND METHODS: We
      studied 64 cases (male 53, female 11), 49-79 years. CRC was measured
      preoperatively using acetazolamide loading Xenon CT CBF examination (XeCT).
      Hypothermia (34-35 C) was induced during surgery in a patient with no CRC.
      Anesthesia was maintained the night after surgery and the systolic blood pressure
      was controlled below 120 mmHg. RESULTS: CRC was absent in 10 patients.
      Postoperative CT did not reveal any hemorrhage or brain swelling. One patient
      experienced a transient restless state. DISCUSSION: and conclusions: Cerebral
      hyperperfusion syndrome has been reported in 0.3 approximately 6.0% of patients
      following carotid endarterectomy (vs 1.6% in our study without hemorrhage or
      brain swelling). These data suggest that information on CRC could be useful for
      selection and perioperative management of patients during carotid endarterectomy.

PMID- 16424834
TI  - Assessment of acute spontaneous intracerebral hematoma by CT perfusion imaging.
AB  - A single-section deconvolution-derived computerized tomographic perfusion imaging
      was performed in 45 patients (22 male and 23 female; mean age=69.89+/-10.07
      years) with acute supratentorial spontaneous intracerebral hemorrhage. Mean rCBF
      and rCBV were lower in the hemorrhagic core than in the perihematomal low density
      area (p<0.001), and in the perihematomal low density area than in normal
      appearing brain parenchyma (p<0.001). Mean rMTT values were higher in
      perihematomal low density area than in normal appearing area (p<0.01) and in both
      hemorrhagic and perihematomal area than in controlateral ROI (p<0.001). There
      were no differences in rMTT mean values between hemorrhagic core and
      perihematomal area, as well as between normal appearing and controlateral areas.
      We found a concentric distribution of all CT perfusion parameters characterized
      by an improvement from the core to the periphery, with low perihematomal rCBF and
      rCBV values suggesting edema formation.

PMID- 16424835
TI  - Threshold of regional cerebral blood flow for infarction in patients with acute
      cerebral ischemia.
AB  - Threshold of regional cerebral blood flow (rCBF) for cerebral tissue survival in
      relation to time was studied in patients with acute cerebral ischemia with xenon
      enhanced computed tomography (XeCT). Case 1: A 58-year-old man with right
      hemiparesis, total aphasia and a high intensity area of 1 cm 2 in the left insula
      on diffusion weighted image underwent XeCT CBF study before and after intra
      arterial local thrombolytic therapy (IALT) on the occluded middle cerebral artery
      (MCA) 4 hours and 7 hours after stroke onset, respectively. Case 2: A 65-year-old
      woman with recurrent transient ischemic attacks (TIAs) caused by severe stenosis
      of the left MCA underwent XeCT CBF study 5 hours after onset of the last attack.
      XeCT was conducted by 5-min wash-in method. In Case 1 the rCBF in the pre-IALT
      MCA territory was 4 to 19 ml/100 g/min. The area where rCBF in the post-IALT
      increased to above 15 ml/100g/min were saved, but the other area where it
      remained in the 9 to 14 ml/100 g/min evolved into infarct on subsequent CT
      scan/MR (magnetic resonance) imaging. The patient was discharged with only mild
      motor dysphasia. In Case 2 the left corona radiata showed rCBF of 7 ml/100 g/min
      and this area evolved into infarct on MR imaging. The patient was discharged home
      with right hemiparesis. Our results showed validity of the rCBF threshold in
      acute cerebral ischemia reported by Jones et al. Residual rCBF in the acute stage
      of cerebral ischemic stroke can predict the fate of the lesion.

PMID- 16424836
TI  - Internal carotid blood flow and cerebral hemispheric perfusion in patients with
      subarachnoid haemorrhage: a study of the quantix/NDtrade mark system and CT
      perfusion technology.
AB  - OBJECTIVE: To assess whether carotid blood flow measurements predict
      abnormalities in cerebral hemispheric perfusion. DESIGN: The Quantix/NDTM system
      was used to measure carotid artery blood flow in nine patients with subarachnoid
      haemorrhage who underwent CT perfusion scanning. RESULTS: No significant
      correlation was found between internal carotid artery blood flow and ipsilateral
      cerebral hemispheric perfusion (013, p>0.05) but there was a statistically
      significant correlation between total internal carotid and global cerebral
      perfusion (0.63, p<0.05). CONCLUSIONS: This is the first report comparing the
      Quantix/NDTM system with CT perfusion. Our data do not show a statistically
      significant correlation between extracranial blood flow and cerebral hemispheric
      perfusion. This is in contrast to two previous studies where Quantix/NDTM
      measurements were compared with measurements of cerebral perfusion using the
      Xenon clearance technique.

PMID- 16424837
TI  - Speech activation SPECT and plasticity of language networks.
AB  - Neuronal activity might be measured by regional cerebral blood flow (rCBF) Single
      Photon Emission Computed Tomography (SPECT) as there is a close relationship
      between neuronal activity and rCBF changes. In order to study the hemispheric
      dominance for language and the plasticity of language networks by measuring the
      rCBF rest and language activation SPECT studies were performed in the presurgical
      evaluation of ten right-handed and two left handed patients with brain lesions of
      the dominant hemisphere. A special group of hemisphere-specific neuropsychologic
      tasks were used for activation, after a proper psychologic conditioning. The rCBF
      results were calculated by comparing the rest and activation SPECT data using a
      special regions of interest program and asymmetry index (AI). We compared the
      results of speech-activation to the results of clinical, morphological (MRI), and
      postoperative data. In controls, significant activation was found in Brodmann's
      area 44 and 45, contralateral cerebellum, superior middle and posterior temporal
      gyrus. In patients, additional regions of activation were seen in contralateral
      frontal and temporal regions, and in ipsilateral temporal region. AIs of the
      cerebellum demonstrated a negative correlation with hemispheric dominance for
      language. In conclusion, significant changes in rCBF in or adjacent to the
      eloquent areas with various patterns of rCBF changes of the additional regions
      demonstrate the close relationship between neuronal activity and cerebral blood
      flow, that can be measured by SPECT.

PMID- 16424838
TI  - Bedside microdialysis reflects dysfunction of cerebral energy metabolism in
      patients with aneurysmal subarachnoid hemorrhage as confirmed by 15 O-H2 O-PET
      and 18 F-FDG-PET.
AB  - OBJECTIVE: To compare microdialysis (MD) and positron emission tomography (PET)
      in the detection of ischemia in aneurysmal subarachnoid hemorrhage (SAH)
      patients. METHODS: 15 SAH patients (13F/2M, 48+/-13 years, WFNS Grade I-V) were
      prospectively included in the study. A MD-catheter was inserted into the brain
      parenchyma most likely to be affected by vasospasm directly after aneurysm
      clipping. Glucose, pyruvate, lactate, glutamate and glycerol were analyzed hourly
      (CMA 600). 15O-H2O-PET scans (n=10) and 18F-FDG-PET scans (n=13) were performed
      between the day 2 and 17 after SAH. 15O-H2O-PET data were merged with CT scans to
      provide quantification of rCBF within the MD-ROI (rCBFMD; Amira, ZIB Berlin,
      Germany). 18F-FDG-PET data were evaluated visually by visual analysis. RESULTS:
      Regions of glucose hypometabolism were observed in 10 patients with symptoms of
      ischemia. Their rCBF was lower compared to asymptomatic patients (p<0.05). The MD
      levels of glutamate, lactate, the L/P ratio and glycerol were significantly
      higher in symptomatic than asymptomatic patients (p<0.05). Out of all measured MD
      parameters, glutamate showed the closest correlation with rCBF (r=-0.66,
      p=0.014). Microdialysis parameters were well correlated with glucose
      hypometabolism (18F-FDG-PET) and symptoms of ischemia. However, the threshold for
      a metabolic derangement was above the limits of cerebral ischemia defined by PET.
      CONCLUSION: MD is a useful tool to monitor ischemia, especially in patients with
      high-grade SAH.

PMID- 16424839
TI  - Hyperperfusion syndrome after supraaortic vessel interventions and bypass
      surgery.
AB  - Cerebral hyperperfusion and hemorrhage is a recognized complication of
      endarterectomy, aortocarotid bypass surgery or angioplasty and stenting of the
      carotid or vertebral artery. We performed 87 balloon angioplasty, stenting and
      bypass surgery of arteries supplying the brain over the last 15 years. We have
      found 6 cases of hyperperfusion syndrome in a total of 87 procedures. So the
      incidence of hyperperfusion was noted as 6.89%. Two cases occurred after two
      combined procedures in a single sitting. Hyperperfusion syndrome is a well-known
      complication of craniocervical revascularisation procedures. But with proper
      care, including strict post procedural control of blood pressure and staged
      procedure in case of multiples vessel stenosis, these complications can be
      largely avoided.

PMID- 16424840
TI  - The less incisional retroperitoneal approach for abdominal aortic aneurysm repair
      to prevent postoperative flank bulge.
AB  - One of the postoperative complications of retroperitoneal incision is a flank
      bulge that is suggested to be caused by 11th intercostal nerve injury leading to
      denervation of the ipsilateral muscles. To avoid this complication, we have tried
      to minimize retroperitoneal incision for abdominal aortic aneurysm (AAA) repair.
      The feasibility of the less incisional retroperitoneal approach for the repair of
      AAA to prevent postoperative flank bulge was investigated. Twenty-seven patients
      undergoing elective repair for infrarenal AAA through the left retroperitoneal
      approach were divided into group-L (less incision: 11.9+/-1.8 cm, n = 7) and
      group-C (conventional incision: 17.8+/-1.9 cm, n = 20). All operations were
      performed by a traditional hand-sewn anastomosis without laparoscopic support.
      Five bifurcated grafts were used in group-L and 15 in group-C. The postoperative
      course of all patients was uneventful except that one patient in group-C required
      reoperation for bleeding. Intraoperative parameters of both groups were almost
      comparable. All patients in group-L were extubated in the operating theater,
      whereas it was possible only for 11 patients in group-C. Resumption of
      alimentation was significantly earlier in group-L (P = 0.0117). There was no
      significant difference in postoperative hospital stay between groups. No late
      flank bulge was experienced. Significant late atrophy of the left rectus muscle
      (left/right thickness-ratio = 0.59+/-0.24) was seen in group-C (P = 0.0042 vs
      preoperative value), which was not observed in group-L (P = 0.0008 between
      groups). The less incisional retroperitoneal AAA repair seems feasible and safety
      technique that might prevent postoperative flank bulge and reduce surgical
      stress.

PMID- 16424841
TI  - Graft insertion technique for distal anastomosis in cases of ascending aortic
      aneurysm.
AB  - We describe a simple and reliable technique of making a secure graft for aorta
      anastomosis, involving sandwiching the friable aortic wall between the graft and
      a Teflon strip. This technique makes possible a secure anastomosis with the
      distal friable tissue and prevents bleeding from the junction.

PMID- 16424842
TI  - Influence of venous drainage and hemofiltration on hypercirculatory instability
      after high volume crystalloid cardioplegia during coronary artery bypass surgery.
AB  - AIM: The etiology of hypercirculatory instability following cardiac surgery with
      cardiopulmonary bypass has not yet been completely investigated and its clinical
      impact remains unclear. This prospective study was undertaken in order to
      investigate the impact of the systemic infusion of high volume crystalloid
      cardioplegia on the incidence of hypercirculatory instability and inflammatory
      mediator release in patients undergoing coronary artery bypass grafting. METHODS:
      Forty patients with single-atrial cannulation (group A), 40 patients with single
      atrial cannulation and intraoperative hemofiltration (group B), and 40 patients
      with bicaval cannulation and complete removal of the cardioplegic solution from
      the right atrium (group C) were analyzed for hemodynamic changes and inflammatory
      mediator release until the postoperative day 2. Myocardial protection was
      performed using 2,000 mL cold crystalloid cardioplegia. RESULTS: A higher
      incidence of hypercirculatory instability in group A (39.2%) and B (42.8 %) was
      noted when compared to group C (18%, P = 0.032). Cardiac index was lower in group
      C when compared with group A (P = 0.001; 95% CI: 4.1, 15.57) and group B (P =
      0.02; 95% CI: 1.13, 15.25). Systemic vascular resistance was higher in group C
      when compared with group A (P = 0.0001; 95% CI: 7108.7, 3131) and group B (P <
      0.005; 95% CI 7598.9; 2830.6). High levels of tumor necrosis factor alpha,
      interleukin-6, interleukin-8, interleukin-10, and intercellular adhesion molecule
      1 with no significant differences between the groups were measured early
      postoperative. CONCLUSIONS: High volume crystalloid cardioplegia under use of
      single-atrial venous cannulation is associated with a higher incidence of
      hypercirculatory failure. Hemofiltration during cardiopulmonary bypass offers no
      benefit on the incidence of hypercirculatory instability and to the release of
      inflammatory mediators.

PMID- 16424843
TI  - The supportive value of pre-bypass L-glutamate loading in patients undergoing
      coronary artery bypass grafting.
AB  - AIM: Experimental studies have demonstrated that an exogenous supply of glutamate
      improves mechanical function and recovery of ischemic myocardium. The aim of the
      present study was to investigate the effect of myocardial pre-bypass loading with
      glutamate on myocardial protection during global ischemia and reperfusion of
      patients undergoing coronary artery bypass grafting (CABG). METHODS: The study
      was double blinded. Twenty patients undergoing elective CABG were randomized to
      receive L-glutamate (n = 10) or normal saline (n = 10). Intracellular levels of
      glutamate, ATP and lactate were measured in left ventricular biopsies collected
      10 min after aortic clamp release. Hemodynamic data, and postoperative release of
      CK-MB and troponin T were also measured. RESULTS: Pre-bypass administration of
      glutamate resulted in myocardial glutamate loading since glutamate levels were
      significantly higher in the glutamate group of patients than in controls (18.6 +/
      3.1 versus 8.7 +/- 1.2 microg/g tissue, P < 0.001). In the same group ATP levels
      were also significantly higher (2.4 +/- 0.7 versus 1.5 +/- 0.4 microg/g tissue, P
      < 0.05) and lactate levels significantly less than in controls (6.9 +/- 1.9
      versus 12.0 +/- 2.1 microg/g tissue, P < 0.001). Glutamate patients had
      statistically significantly superior post-bypass hemodynamic performance (cardiac
      index, left ventricular stroke work index, systemic vascular resistance and
      pulmonary vascular resistance). Statistically significantly lower levels of CK-MB
      (6 h postoperative), total and peak CK-MB, troponin T (24 h postoperative), and
      total troponin T were found in the glutamate group. CONCLUSIONS: The results of
      this preliminary study indicate that pre-bypass intravenous administration of
      glutamate in patients undergoing CABG has a supportive effect on myocardial
      metabolism during global ischemia and reperfusion, improves patients'
      postoperative hemodynamic performance and reduces postoperative cardiac enzyme
      release.

PMID- 16424844
TI  - Thoracic epidural anesthesia preserves myocardial function during intraoperative
      and postoperative period in coronary artery bypass grafting operation.
AB  - AIM: The purpose of this study was to investigate the effect of thoracic epidural
      anesthesia (TEA) in patients with poor ventricular function undergoing
      conventional coronary artery bypass graft surgery (CABG) during the
      intraoperative and the postoperative period. METHODS: Eighty patients (n = 80)
      undergoing elective CABG surgery with cardiopulmobary bypass (CPB) were divided
      into 4 groups: 1) General anesthesia (GA) plus poor ventricular (PV) function
      patients (Group GA plus PV) (n = 20), ejection fraction (EF) = or <40%; 2) GA
      plus good ventricular (GV) function patients (Group GA plus GV) (n = 20), EF
      >40%; 3) Thoracic epidural anaesthesia (TEA)+GA, poor ventricular function
      patients (Group TEA+GA plus PV) (n = 20), EF = or <40%; 4) TEA+GA, good
      ventricular function patients (Group TEA+GA plus GV) (n = 20), EF >40%. RESULTS:
      Within groups, at 4 h after the end of CPB, in the Group TEA+GA plus PV and Group
      TEA+GA plus GV, the cardiac index values were significantly higher than baseline
      values; P < 0.05, whereas no difference was found in the Group GA plus PV and
      Group GA plus GV. According to Tukey test, using repeated measures, between trend
      of groups, the cardiac index values were significantly different P < 0.05. In the
      Group TEA+GA plus PV, cardiac index values were significantly higher than the
      Group GA plus PV, P < 0.05. But in the Group GA plus GV, cardiac index values
      were not significantly different than the Group TEA+GA plus GV. The incidence of
      reperfusion ventricular fibrillation (VF) after release of aortic cross-clamp, in
      the Group TEA+GA plus PV (4 of 20 patients: 20%) was significantly lower than in
      the Group GA plus PV (11 of 20 patients: 55%); P < 0.05. The incidence of
      reperfusion VF after release of aortic cross-clamp, in the Group TEA+GA plus GV
      (5 of 20 patients: 25%) was not significantly different than in the Group GA plus
      GV (10 of 20 patients: 50%); NS. CONCLUSIONS: TEA seems to be effective in
      patients with poor left ventricular function. Our results (improved cardiac
      index, reduced arrhythmias after release of aortic clamp and decreased inotropic
      requirement) are better with TEA, particularly in patients with poor left
      ventricular function.

PMID- 16424845
TI  - Myocardial protection with insulin cardioplegia: who can really benefit?
AB  - AIM: The aim of the study was to evaluate the effects on myocardial protection of
      insulin-enriched warm blood cardioplegia (IWBC) in coronary artery bypass
      grafting (CABG) and in subgroups of patients with associated cardiac co
      morbidities. METHODS: Between May 2000 and December 2002, 268 consecutive
      patients underwent CABG with warm blood cardioplegia (group A) or IWBC (10 UI/L)
      (group B). Hospital outcome, ECG, echocardiography and biochemical markers of
      ischemia were compared. Differences between subgroups of patients with unstable
      angina (UA), ventricular hypertrophy (VH) and diabetes were assessed. RESULTS:
      Hospital mortality, incidence of postoperative myocardial infarction and low
      output syndrome, IABP requirement, postoperative atrial fibrillation, in-hospital
      and in-ITU stay, postoperative recovery of left ventricular function and enzyme
      leakage did not show differences between the 2 groups; inotropic support was
      lower in IWBC. Moreover, patients with UA and IWBC showed a lower troponin I
      (TnI) (12 h: 0.82+/-0.57 ng/mL vs 2.56+/-1.18, P < 0.0001; 24 h: 0.71+/-0.64 vs
      2.16+/-1.52, P < 0.0001; 48 h: 0.69+/-1.13 vs 1.79+/-1.43, P = 0.001; 72 h:
      0.44+/-0.83 vs 1.01+/-1.02, P = 0.001), lower incidence of atrial fibrillation
      (4.2% versus 60.6%; P < 0.0001) and intraoperative defibrillation (0% versus
      27.3%; P = 0.007). Furthermore, patients with VH treated with IWBC showed lower
      level of TnI (12 h: 0.41+/-0.32 ng/mL vs 2.93+/-0.67, P < 0.0001; 24 h: 0.37+/
      0.45 vs 2.40+/-1.28, P < 0.0001; 48 h: 0.22+/-0.18 vs 1.95+/-1.33, P < 0.0001; 72
      h: 0.12+/-0.12 vs 1.31+/-1.56, P < 0.0001), lower atrial fibrillation (6.5% vs
      48%, P < 0.0001) and ventricular defibrillation (0% vs 20%, P = 0.011).
      CONCLUSIONS: Insulin addiction to blood cardioplegia does not show any benefit in
      the global population and in diabetics; nevertheless, better myocardial
      protection can be demonstrated in patients with unstable angina and left
      ventricular hypertrophy.

PMID- 16424847
TI  - Postoperative atrial fibrillation independently predicts prolongation of hospital
      stay after cardiac surgery.
AB  - AIM: Postoperative atrial fibrillation (AF) occurs in up to 50% of cardiac
      surgery patients and represents the most common postoperative arrhythmic
      complication. A reduction of the length of hospital stay is a desirable goal in
      preventive strategies of postoperative AF. The aim of the present investigation
      was to determine whether prolonged postoperative hospital stay associated with AF
      after cardiac surgery surgery is attributable to the arrhythmia itself or to
      baseline characteristics of patients who develop AF. METHODS: Patients undergoing
      elective cardiac surgery in the absence of heart failure and significant left
      ventricular dysfunction (n = 253; average age 65+/-11 years) were recruited to
      the present prospective study. Midline sternotomy procedures with standard
      surgical techniques for normothermic cardiopulmonary bypass in coronary artery
      bypass grafting and valvular surgery were used. RESULTS: A total of 99 patients
      (39.1%) of the study population developed AF during the postoperative period. AF
      patients were older and more likely to have surgery for valvular heart disease
      and less likely to have antiarrhythmic drugs including beta-adrenergic blockers
      than patients without AF, but both patients with and without AF had similar body
      mass index and duration of surgery. Postoperative hospital stays were longer in
      patients with AF compared to those without AF (14.9+/-5.7 vs 10.6+/-3.6,
      respectively; P = 0.001). Multivariate analysis, adjusted for age and
      postoperative complications, demonstrated that postoperative hospital stay was
      14.2+/-5.3 days in patients with AF and 10.8+/-3.8 days in patients without AF (P
      < 0.01). Treatment with oral antiarrhythmic drugs that reduce AF is associated
      with a reduction of postoperative hospital stay. CONCLUSIONS: Despite baseline
      characteristics differed between patients with and without postoperative AF, most
      of the prolongation of hospital stay can be attributed to the rhythm disturbance
      itself.

PMID- 16424846
TI  - Blood warm reperfusion: a necessary adjunct to heart-valve surgery in low-risk
      patients?
AB  - AIM: The aim of this prospective, randomized study was to determine whether blood
      warm reperfusion improves myocardial protection provided by cold crystalloid
      cardioplegia in patients undergoing first-time elective heart-valve surgery,
      using cardiac troponin I release as the criterion for evaluating the adequacy of
      myocardial protection. METHODS: Seventy patients with a left ventricular ejection
      fraction greater than 40% were randomly assigned to 1 of 2 myocardial protection
      strategies: 1) cold crystalloid cardioplegia with no reperfusion or 2) cold
      crystalloid cardioplegia followed by 2-minute blood warm reperfusion before
      aortic unclamping. Cardiac troponin I concentrations were measured in serial
      venous blood samples drawn immediately prior to cardiopulmonary bypass and after
      aortic unclamping at 6, 9, 12, and 24 h. RESULTS: Randomization produced 2
      equivalent groups. The total amount of cardiac troponin I released (7.17+/- 14.8
      mg in the crystalloid cardioplegia with no reperfusion group and 5.82+/-4.66 mg
      in the crystalloid cardioplegia followed by blood warm reperfusion group) was not
      different (P > 0.2). Cardiac troponin I concentration did not differ for any
      sample in either of the 2 groups. The total amount of cardiac troponin I released
      was higher in patients who required inotropic support (9.14 +/-16.2 mg) than
      those who did not (4.73+/-4.52 mg; P = 0.009). CONCLUSIONS: Our study shows that
      adding blood warm reperfusion to cold crystalloid cardioplegia provides no
      additional myocardial protection in low-risk patients undergoing heart-valve
      surgery.

PMID- 16424850
TI  - Acute prosthetic valve dysfunction detected by intraoperative transesophageal
      echocardiography.

PMID- 16424849
TI  - Biatrial myxoma: surgical experience of a rare cardiac tumor.

PMID- 16424848
TI  - Papillary fibroelastoma of the right atrium: an atypical presentation. A case
      report and review of the literature.
AB  - Papillary fibroelastomas are a rare form of benign cardiac neoplasm. While the
      majority of these lesions are asymptomatic and found incidentally via
      echocardiography or cardiac catheterization, those occurring on left-sided
      structures may become clinically important producing symptoms of syncope, angina,
      myocardial infarction, and sudden death. These masses also have the propensity to
      embolize resulting in transient ischemic attacks and strokes. Most papillary
      fibroelastomas are found on valvular structures and currently there are only 4
      published case reports of these lesions occurring in the right atrium. Of these
      reports, only 3 have been presented as arising on the right atrial free wall.
      This case report presents the 54th known case of a papillary fibroelastoma
      occurring in the right atrium and the 4th to be reported as developing from the
      right atrial free wall. A review of the literature as well as the histogenesis,
      diagnosis, and therapy of this rare entity are discussed.

PMID- 16424851
TI  - Aorto-cutaneous fistula: complication of coronary artery bypass graft operation.

PMID- 16424852
TI  - Management of an aortic wall ulcer after an aortic dissecting hematoma.
AB  - We report the case of a 40-year-old woman who presented with an ulcer of the
      descending aorta 9 months after ascending aortic surgery for intramural aortic
      hematoma, which was treated surgically with a supra-coronary aortic replacement.
      Treatment of the second aortic lesion and the choice between endovascular or
      surgical approaches are discussed.

PMID- 16424853
TI  - Public health response to Hurricanes Katrina and Rita--Louisiana, 2005.
AB  - On August 24, 2005, Tropical Depression 12 became Tropical Storm Katrina, the
      11th named storm of the 2005 Atlantic hurricane season. Late on August 25,
      Katrina made initial landfall in south Florida as a category 1 hurricane on the
      Saffir-Simpson Hurricane Scale. Katrina strengthened rapidly upon reaching the
      Gulf of Mexico, attaining category 5 intensity. On August 29, Hurricane Katrina
      struck the Gulf Coast near the Louisiana-Mississippi border as a category 3
      hurricane. The effect of earlier category 5 wind speeds on Gulf waters and the
      massive size of the storm combined to create devastating storm-surge conditions
      for coastal Mississippi, Louisiana, and Alabama and damage as far east as the
      Florida panhandle. Storm-induced breeches in the New Orleans levee system
      resulted in the catastrophic flooding of approximately 80% of that city.
      Hurricane Katrina was the deadliest hurricane to strike the United States since
      1928. Preliminary mortality reports indicate approximately 1,000 Katrina-related
      deaths in Louisiana, 200 in Mississippi, and 20 in Florida, Alabama, and Georgia.

PMID- 16424854
TI  - Two cases of toxigenic Vibrio cholerae O1 infection after Hurricanes Katrina and
      Rita--Louisiana, October 2005.
AB  - Louisiana was struck by Hurricane Katrina on August 29, 2005, and by Hurricane
      Rita on September 24, 2005. The two hurricanes caused unprecedented damage from
      wind and storm surge to the Louisiana Gulf Coast region, and levee breaks
      resulted in flooding of large residential areas in and around New Orleans. With
      the flooding, an immediate public health concern was the potential for outbreaks
      of infectious diseases, including cholera. Nearly all Vibrio infections in the
      United States are caused by noncholeragenic Vibrio species (e.g., V.
      parahaemolyticus, V. vulnificus, and non-O1, non-O139 V. cholerae). Cases of
      cholera rarely occur in the United States, and cholera epidemics, such as those
      reported in certain developing countries, are unlikely, even with the extreme
      flooding caused by the two hurricanes. This report describes the investigation by
      the Louisiana Office of Public Health and CDC into two cases of toxigenic V.
      cholerae O1 infection in a Louisiana couple; the cases were attributed to
      consumption of undercooked or contaminated seafood. Although noncholeragenic
      Vibrio illnesses were reported in 22 residents of Louisiana and Mississippi after
      Hurricane Katrina, no epidemic of cholera was identified, and no evidence exists
      of increased risk to Gulf Coast residents.

PMID- 16424855
TI  - Surveillance in hurricane evacuation centers--Louisiana, September-October 2005.
AB  - On August 29, 2005, Hurricane Katrina made landfall southeast of New Orleans,
      Louisiana. Before the arrival of Katrina, New Orleans and surrounding parishes
      were under a mandatory evacuation order. Because of this order and subsequent
      flooding, approximately 400,000 residents became displaced. On August 28,
      approximately 50,000 persons began moving into evacuation centers (ECs)
      throughout the state of Louisiana (American Red Cross, unpublished data, 2005).
      The Louisiana Department of Health and Hospitals, Office of Public Health (LAOPH)
      recognized the need for communicable disease surveillance in the ECs. Although
      the LAOPH Internet-based Reportable Disease Database was intact and never stopped
      functioning after the hurricane, LAOPH determined that the large number of ECs
      warranted active surveillance. On September 8, LAOPH, with the cooperation of the
      American Red Cross (ARC) and the U.S. Public Health Service, initiated statewide
      daily syndromic surveillance for communicable diseases in the ECs. In addition to
      collecting and analyzing data on communicable disease syndromes, data were
      collected on chronic medical conditions, injuries, and mental health conditions.
      This report summarizes the development and implementation of this surveillance
      system in the ECs, the types of data collected and how they were used, and the
      limitations of the data.

PMID- 16424856
TI  - Injury and illness surveillance in hospitals and acute-care facilities after
      Hurricanes Katrina And Rita--New Orleans area, Louisiana, September 25-October
      15, 2005.
AB  - In response to Hurricane Katrina, CDC and the Louisiana Department of Health and
      Hospitals (LDHH) implemented active surveillance on September 9, 2005, to monitor
      for injuries and illnesses at functioning hospitals and other acute-care
      facilities in the greater New Orleans area (Jefferson, Orleans, Plaquemines, St.
      Bernard, St. Charles, and St. Tammany parishes). On September 20, the system was
      interrupted because of mandatory evacuation for Hurricane Rita. Surveillance was
      reestablished on September 24, and repopulation of Orleans Parish began on
      September 30. This report updates a previous report on injuries and illness
      surveillance during September 8-25, 2005, after Hurricane Katrina and describes
      frequencies of these events during the days after Hurricane Rita and during
      repopulation of the city. The results indicate that 17,446 visits occurred at
      participating facilities during this period. Whereas the proportion of relief
      workers who had acute respiratory illnesses and unintentional injuries was higher
      compared with residents, the proportion of falls and motor-vehicle crashes among
      relief workers was lower. Moreover, although the collection of detailed data
      using a paper-based active surveillance system was required in response to
      Hurricane Katrina, the burden of this system required the implementation of an
      electronic syndromic surveillance system, which is more sustainable.

PMID- 16424857
TI  - Assessment of health-related needs after Hurricanes Katrina and Rita--Orleans and
      Jefferson Parishes, New Orleans area, Louisiana, October 17-22, 2005.
AB  - Residents returning home after natural disasters face numerous physical, mental,
      and social challenges. Seven weeks after Hurricane Katrina struck the New Orleans
      area in Louisiana, causing levees to break and large sections of the city to
      flood, local authorities had reopened most of Jefferson Parish and much of
      Orleans Parish to residents. To identify health-related needs among returning
      parish residents, state and local public health and mental health agencies and
      CDC conducted an assessment of living conditions, access to basic services, and
      physical and mental health status. This report describes the results of that
      assessment, which determined that, approximately 7 weeks after Hurricane Katrina
      made landfall, 20.2% of housing units lacked water, 24.5% had no electricity,
      43.2% had no telephone service, and 55.7% of households contained one or more
      members with a chronic health condition. In addition, 49.8% of adults exhibited
      levels of emotional distress, indicating a potential need for mental health
      services. As a result of these findings, the Louisiana Office of Mental Health
      established a crisis-counseling program to provide interventions and support to
      hurricane survivors. Community assessments after natural disasters can identify
      health-related needs and guide public health interventions.

PMID- 16424858
TI  - Health concerns associated with mold in water-damaged homes after Hurricanes
      Katrina and Rita--New Orleans area, Louisiana, October 2005.
AB  - After Hurricanes Katrina and Rita made landfall on August 29 and September 24,
      2005, respectively, large sections of New Orleans (Orleans Parish) and the three
      surrounding parishes (Jefferson, Plaquemines, and St. Bernard) were flooded for
      weeks, leading to extensive mold growth in buildings. As residents reoccupied the
      city, local health-care providers and public health authorities were concerned
      about the potential for respiratory health effects from exposure to water-damaged
      homes. On October 6, CDC was invited by the Louisiana Department of Health and
      Hospitals (LDHH) to assist in documenting the extent of potential exposures. This
      report summarizes the results of that investigation, which determined that 46% of
      inspected homes had visible mold growth and that residents and remediation
      workers did not consistently use appropriate respiratory protection. Public
      health interventions should emphasize the importance of safe remediation
      practices and ensure the availability of recommended personal protective
      equipment.

PMID- 16424859
TI  - High levels of adamantane resistance among influenza A (H3N2) viruses and interim
      guidelines for use of antiviral agents--United States, 2005-06 influenza season.
AB  - An estimated 200,000 persons are hospitalized each year and 36,000 persons die
      from complications of influenza in the United States. The cornerstone of
      influenza prevention is annual vaccination. However, antiviral drugs are an
      important adjunct to vaccination for influenza prevention and control. Two
      classes of antiviral medications are available currently: adamantanes or M2 ion
      channel inhibitors (i.e., amantadine and rimantadine) and neuraminidase
      inhibitors (i.e., oseltamivir and zanamivir). The adamantanes are active against
      only influenza A viruses and are used for both treatment and chemoprophylaxis of
      influenza A, whereas the neuraminidase inhibitors are active against both
      influenza A and B viruses. Zanamivir is not approved for chemoprophylaxis of
      influenza in the United States. This report describes new findings regarding the
      resistance to adamantanes of influenza A viruses currently circulating in the
      United States and provides interim recommendations that these drugs not be used
      during the remainder of the 2005-06 influenza season. Amantadine also is used to
      treat symptoms of Parkinson disease and may continue to be used for this
      indication.

PMID- 16424860
TI  - Lack of association between the C825T polymorphism in G-protein beta-3 subunit
      and arterial blood pressure levels in cardiovascular disease free individuals:
      the ATTICA epidemiological study.

PMID- 16424861
TI  - Adherence to antihypertensive medication and association with patient and
      practice factors.

PMID- 16424863
TI  - Inositide-specific phospholipase c beta1 gene deletion is a rare event in
      myelodysplastic syndromes.

PMID- 16424864
TI  - Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile
      myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already
      exists at onset.
AB  - Among 11 JMML children, two had an abnormal karyotype, and nine had a normal
      karyotype at onset. In one patient with trisomy 8 and four patients with a normal
      karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6
      mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in
      situ hybridization disclosed that an abnormal clone existed in approximately 3-6%
      of bone marrow cells at onset or before 6-MP therapy in all the four cases
      examined, and increased to approximately 12-90% during the treatment. In culture
      with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal
      clones that proliferated during 6-MP therapy possessed significantly less
      sensitivity to the antimetabolite, compared with cells that decreased in numbers
      after the therapy. A PTPN11 mutation was detected in all of granulocyte
      macrophage colonies irrespective of karyotypic aberration in one patient, whereas
      approximately 80% of erythroid colonies and 20% of mixed colonies possessed
      neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of
      chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases
      may result, in part, from the growth of a 6-MP-refractory clone that already
      exists at onset. It is possible that treatment with 6-MP promotes progression of
      the disease.

PMID- 16424865
TI  - A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma.

PMID- 16424867
TI  - High incidence of Notch-1 mutations in adult patients with T-cell acute
      lymphoblastic leukemia.

PMID- 16424866
TI  - Low or absent SPARC expression in acute myeloid leukemia with MLL rearrangements
      is associated with sensitivity to growth inhibition by exogenous SPARC protein.
AB  - Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular
      glycoprotein with growth-inhibitory and antiangiogenic functions. Although SPARC
      has been implicated as a tumor suppressor in humans, its function in normal or
      malignant hematopoiesis has not previously been studied. We found that the
      leukemic cells of AML patients with MLL gene rearrangements express low to
      undetectable amounts of SPARC whereas normal hematopoietic progenitors and most
      AML patients express this gene. SPARC RNA and protein levels were also low or
      undetectable in AML cell lines with MLL translocations. Consistent with its tumor
      suppressive effects in various solid tumor models, exogenous SPARC protein
      selectively reduced the growth of cell lines with MLL rearrangements by
      inhibiting cell cycle progression from G1 to S phase. The lack of SPARC
      expression in MLL-rearranged cell lines was associated with dense promoter
      methylation. However, we found no evidence of methylation-based silencing of
      SPARC in primary patient samples. Our results suggest that low or absent SPARC
      expression is a consistent feature of AML cells with MLL rearrangements and that
      SPARC may function as a tumor suppressor in this subset of patients. A potential
      role of exogenous SPARC in the therapy of MLL-rearranged AML warrants further
      investigation.

PMID- 16424868
TI  - Pro-apoptotic properties of hyperforin in leukemic cells from patients with B
      cell chronic lymphocytic leukemia.
AB  - The effects of the hyperforin (HF), a natural phloroglucinol purified from
      Hypericum perforatum, were investigated ex vivo on leukemic cells from patients
      with B-cell chronic lymphocytic leukemia (B-CLL). HF was found to promote
      apoptosis of B-CLL cells, as shown by time- and dose-dependent stimulation of
      phosphatidylserine externalization and DNA fragmentation, by disruption of the
      mitochondrial transmembrane potential, caspase-3 activation and cleavage of the
      caspase substrate PARP-1. Moreover, HF-induced downregulation of Bcl-2 and Mcl-1,
      two antiapoptotic proteins that control mitochondrial permeability. HF also
      downregulated two proteins which are overexpressed by B-CLL patients' cells, the
      cell cycle inhibitor p27kip1 through caspase-dependent cleavage into a p23 form,
      and the nitric oxid (NO) synthase of type 2 (inducible NO synthase). This latter
      was accompanied by reduction in the production of NO known to be antiapoptotic in
      B-CLL cells. Preventing effects of the general caspase inhibitor z-VAD-fmk
      indicated that HF-promoted apoptosis of B-CLL cells was mostly caspase dependent.
      Furthermore, normal B lymphocytes purified from healthy donors appeared less
      sensitive to HF-induced apoptosis than B-CLL cells. These results indicate that
      HF may be of interest in the development of new therapies for B-CLL based on the
      induction of apoptosis and combination with cell cycle-dependent antitumor drugs.

PMID- 16424869
TI  - Cooperation of activating Ras/rtk signal transduction pathway mutations and
      inactivating myeloid differentiation gene mutations in M0 AML: a study of 45
      patients.
AB  - According to a two hit model of leukaemogenesis, the association between acute
      myeloid leukaemia (AML)1 mutations and FLT3 gene alterations has been recently
      described in M0 AML. To further document this model in M0 AML, we screened a
      cohort of 45 patients to find an association between genes implicated in myeloid
      differentiation (AML1, Pu1) and genes contributing to cell proliferation: (FLT3,
      N-RAS, K-RAS, c-KIT, PTPN11). No mutation of the Pu1 gene was observed, whereas
      mutation in the Runt domain of AML1 gene was observed in 12 of 45 patients (27%).
      No point mutation or insertion-deletion in the c-kit gene was found. Three point
      mutations (7%) and 11 internal tandem duplications (22%) were seen in FLT3 gene.
      Two N-Ras and one PTPN11 mutations were found. No significant correlation between
      AML1 mutation and FLT3 alteration was found. On the other hand, abnormal
      cytogenetic findings, especially unfavourable ones, were significantly more
      frequent in patients without detectable molecular abnormality. These findings
      suggest at least two different pathogenetic pathways in M0 AML: one associated
      with AML1 mutation, sometimes in combination with the activating lesion of the
      tyrosine kinase pathway and generally with normal karyotype, and the other with
      unfavourable cytogenetic findings.

PMID- 16424870
TI  - Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease with multiple different
      cytogenetic and molecular aberrations contributing to leukemic transformation. We
      compared gene expression profiles of 4608 genes using cDNA-arrays from 20 AML
      patients (nine with -7/del7q and 11 with normal karyotype) with 23 CD34+
      preparations from healthy bone marrow donors. SKI, a nuclear oncogene, was highly
      up regulated. In a second set of 183 AML patients analyzed with real-time PCR,
      the highest expression level of SKI in AML with -7/del7q could be confirmed. As
      previously described, Ski associates with the retinoic acid receptor (RAR)
      complex and can repress transcription. We wanted to investigate the interference
      of Ski with RARalpha signaling in AML. Ski was co-immunoprecipitated and
      colocalized with RARalpha. We also found that overexpression of wild-type Ski
      inhibited the prodifferentiating effects of retinoic acid in U937 leukemia cells.
      Mutant Ski, lacking the N-CoR binding, was no more capable of repressing RARalpha
      signaling. The inhibition by wild-type Ski could partially be reverted by the
      histone deacetylase blocking agent valproic acid. In conclusion, Ski seems to be
      involved in the blocking of differentiation in AML via inhibition of RARalpha
      signaling.

PMID- 16424872
TI  - Long-term survival data from a phase 3 study of Filgrastim as an adjunct to
      chemotherapy in adults with de novo acute myeloid leukemia.
AB  - We previously reported the results of a double-blind, placebo-controlled study of
      Filgrastim in patients with de novo AML undergoing induction and consolidation
      chemotherapy. The study demonstrated that Filgrastim was effective and well
      tolerated and had no impact on complete remission or survival. We now report
      follow-up data on these patients, assessing long-term effects with emphasis on
      prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients
      were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The
      proportions of deaths were similar in the Filgrastim (83%) and placebo (84%)
      groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years
      placebo; P = 0.97) or median disease-free survival (0.86 years Filgrastim, 0.79
      years placebo; P = 0.52) were evident. Proportional hazard modeling identified
      age, performance status, and French-American-British subtype as independent
      predictors for survival (P < 0.001, P = 0.005, and P = 0.036, respectively),
      whereas cytogenetic status was not (P = 0.118). Filgrastim had no effect on
      overall survival in any of these subgroup analyses as none of the treatment
      comparisons were statistically significant. These findings indicate that
      Filgrastim can be effectively used to support patients with AML undergoing
      induction and consolidation chemotherapy without worsening long-term disease
      outcome.

PMID- 16424874
TI  - Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and
      COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug
      sensitivity and clinical outcome.
AB  - Clinical heterogeneity within t(12;21) or TEL/AML1-positive ALL (25% of childhood
      common/preB ALL) indicates that additional genetic changes might contribute to
      outcome. We studied the relation between additional genetic changes in TEL(ETV6)
      and AML1(RUNX1) (FISH), drug sensitivity (MTT assay) and clinical outcome in 143
      DCOG and COALL-treated t(12;21)-positive ALL patients. Additional genetic changes
      in TEL and AML1 were present in 83% of the patients, and consisted of (partial)
      deletion of the second TEL gene (70%), an extra AML1 gene (23%) or an extra
      der(21)t(12;21) (10%). More than one additional change was observed in 20%.
      Disease-free survival (pDFS) of DCOG patients without additional genetic changes
      (4 years pDFS +/- s.e. 53 +/- 17%) and of those with an extra der(21)t(12;21) (60
      +/- 22%) is poorer than that of compared to patients with other additional
      genetic changes in TEL or AML1 (79 +/- 6%; P-trend = 0.02). This was mainly due
      to the occurrence of early relapses within 2.5 years after the first diagnosis.
      Similar observations were found in the COALL cohort, albeit not significant owing
      to limited follow-up. Multivariate analysis including age, WBC and genetic
      abnormalities in TEL and/or AML1 showed that especially, in vitro resistance to
      prednisolone (hazard ratio 5.78, 95% CI 1.45-23.0; P=0.01) is an independent
      prognostic factor in DCOG- and COALL-treated t(12;21)-positive ALL.

PMID- 16424875
TI  - Monitoring minimal residual disease by quantification of genomic chromosomal
      breakpoint sequences in acute leukemias with MLL aberrations.
AB  - An estimated 10% of acute leukemias carry mixed-lineage leukemia (MLL) fusion
      genes. Approximately 50 different fusion partners of the MLL gene have already
      been molecularly identified. These leukemias are commonly regarded as high-risk
      cases and are treated accordingly with intensified therapy regimens, including
      hematopoietic stem cell transplantation. However, a subset of patients may
      achieve long-term remissions with conventional therapy. Monitoring minimal
      residual disease (MRD) is undoubtedly of great value in clinical decision making,
      also in the pre- and post-transplant setting. Here, we describe a novel method
      for detecting MRD in leukemias with MLL aberrations. The method is based on
      monitoring patient-specific chromosomal breakpoint DNA sequences. This has
      several advantages over other methods that are based either on detecting specific
      RNA molecules of MLL fusion genes or on surrogate markers. An accurate and
      absolute quantification of the MRD level is possible. No reference to
      housekeeping genes is necessary and the target structure is much more stable than
      any mRNA fusion transcript.

PMID- 16424876
TI  - Activating mutations of JAK2V617F are uncommon in t-MDS and t-AML and are only
      observed in atypic cases.

PMID- 16424877
TI  - Population-based demographic study of karyotypes in 1709 patients with adult
      acute myeloid leukemia.
AB  - Few large demographic studies of acute myeloid leukemia (AML) are derived from
      population-based registries. Demographic and karyotypic data were provided for
      AML cases from two regional leukemia registry databases in Scotland and the
      Northern Region of England. A population-based dataset was compiled, comprising
      1709 patients aged >16 years (1235 North England/474 Scotland patients). The most
      common cytogenetic abnormalities involved chromosomes 5 and/or 7 (17%). Patients
      with the following abnormal chromosome 5/7 combinations: -5, del(5q), -5/-7 and
      del(5q)/-7 represented a significantly older population (P < 0.01, ANOVA).
      t(8;21) was the only 'favourable' karyotype found in older age. Karyotypic
      complexity varied within chromosome 5/7 combination groups; those containing -5, 
      5/-7, -5/del(7q), del(5q)/-7 or del(5q)/del(7q) combinations were significantly
      more frequently complex than those containing -7 and del(7q) (P < 0.01, chi2
      test). Additional recurring cytogenetic abnormalities within complex karyotypes
      containing chromosome 5/7 combinations included (in order of frequency),
      abnormalities of chromosomes 17, 12, 3 and 18. Complex karyotypes not involving
      chromosomes 5 or 7 represented 30% of all complex karyotypes, occurred in younger
      patients than those involving chromosomes 5 and 7, and frequently included
      additional trisomy 8 (26%). In conclusion, we describe subgroups within adverse
      karyotypes, with different demographics, degree of complexity and additional
      chromosome abnormalities.

PMID- 16424878
TI  - Stratum-specific expression of human transferrin receptor increases iron in mouse
      epidermis.
AB  - Epidermal desquamation accounts for 20% of the body's iron loss each day. Yet,
      little is known about how iron content in epidermis is regulated. To test the
      importance of the transferrin receptor in regulating iron content in epidermis,
      we created transgenic mice that have stratum-specific expression of the human
      transferrin receptor. The keratin 14 promoter targeted the receptor primarily to
      basal, proliferating keratinocytes; the involucrin (Inv) promoter targeted the
      receptor to suprabasal, differentiating keratinocytes. There were age- and site
      dependent differences in iron content in the epidermis and hair. In both types of
      transgenic mice, epidermal iron content increased with age and at 8 weeks was 2-3
      fold greater in transgenic mice compared to littermate controls. Iron was
      increased up to 2-fold in hair of keratin 14-human transferrin receptor (hTfR)
      transgenics and 30% in Inv-hTfR transgenics. No gross or histological changes
      were seen in transgenic animals with increased iron in the epidermis. Ferritin
      expression, which was low in normal epidermis, was greatly increased in both
      transgenic lines, indicating that it is the likely depot for the extra iron in
      these animals. These data show that control of transferrin receptor expression is
      sufficient to regulate iron content in proliferating or differentiating
      keratinocytes in the epidermis.

PMID- 16424879
TI  - Collagen dysregulation in the dermis of the Sagg/+ mouse: a loose skin model.
AB  - The Sagg/+ mouse is an ethylnitrosourea-derived mutant with a dermal phenotype
      similar to some of the subtypes of Ehlers-Danlos syndrome (EDS) and cutis laxa.
      The dermis of the Sagg/+ mouse has less dense and more disorganized collagen
      fibers compared to controls. The size of extracted Type I dermal collagen was the
      same as that observed in normal skin; however, more collagen could be extracted
      from Sagg/+ skin, which also showed decreased collagen content and decreased
      steady-state levels of alpha1(I), alpha2(I), alpha1(V), and alpha2(V) procollagen
      mRNAs. The biomechanical properties of Sagg/+ skin were significantly decreased
      relative to normal skin. However, there were no significant differences in the
      quantities of the major collagen cross-links, that is,
      dehydrohydroxylysinonorleucine and dehydrohistidinohydroxymerodesmosine between
      Sagg/+ and normal skin. Electron microscopic evaluation of Sagg/+ skin indicated
      that the mutation interferes with the proper formation of collagen fibrils and
      the data are consistent with a mutation in Type V collagen leading to
      haploinsufficiency with the formation of two sub-populations of collagen fibrils,
      one normal and one with irregular shape and a larger diameter. Further study of
      this novel mutation will allow the identification of new mechanisms involved in
      the regulation of normal and pathologic collagen gene expression.

PMID- 16424881
TI  - Enhanced IgE allergic response to Aspergillus fumigatus in CFTR-/- mice.
AB  - To gain insight into aberrant cytokine regulation in cystic fibrosis (CF), we
      compared the phenotypic manifestations of allergen challenge in gut-corrected
      CFTR-deficient mice with background-matched C57Bl6 (B6) mice. Aspergillus
      fumigatus (Af) antigen was used to mimic allergic bronchopulmonary aspergillosis,
      a peculiar hyper-IgE syndrome with a high prevalence in CF patients. CFTR-/-,
      C57BL/6 and FVB/NJ mice were sensitized with Af antigen by serial intraperitoneal
      injections. Control mice were mock sensitized with PBS. Challenges were performed
      by inhalation of Af antigen aerosol. After Af antigen challenge, histologic
      analysis showed goblet cell hyperplasia and lymphocytic infiltration in both
      strains. However, total serum IgE levels were markedly elevated in CF mice.
      Sensitized CF mice showed a five-fold greater IgE response to sensitization as
      compared with B6- and FVB-sensitized controls. Additional littermate controls to
      fully normalize for B6-FVB admixture in the strain background confirmed the role
      of CFTR mutation in the hyper-IgE syndrome. Cytokine mRNA levels of IL-5 and GM
      CSF in the bronchoalveolar lavage (BAL) fluid, and BAL cell differentials
      indicated that CFTR mutation caused a shift from an IL-5-predominant to an IL-4
      predominant cytokine profile. This system models a very specific type of airway
      inflammation in CF and could provide insights into pathogenesis and treatment of
      the disease.

PMID- 16424883
TI  - The year of bird flu.

PMID- 16424884
TI  - Dendritic cells at the host-pathogen interface.
AB  - How DCs integrate information from pathogens, tissues, and innate leukocytes for
      the induction of immune responses was presented at the second International
      Conference on Dendritic Cells at the Host-Pathogen Interface.

PMID- 16424885
TI  - Crosscurrents in HIV-1 evolution.

PMID- 16424886
TI  - Mal-function of TLRs by SOCS.

PMID- 16424887
TI  - Youth has its privileges: maturation inhibits DC cross-priming.

PMID- 16424888
TI  - '3d' effects on global immunity.

PMID- 16424892
TI  - Interobserver reproducibility in the diagnosis of flat epithelial atypia of the
      breast.
AB  - Columnar cell lesions (CCLs) of the breast with low-grade/monomorphic-type
      cytologic atypia are being identified increasingly in biopsies performed owing to
      mammographic microcalcifications. The WHO Working Group on the Pathology and
      Genetics of Tumours of the Breast recently introduced the term 'flat epithelial
      atypia' (FEA) for these lesions. However, the ability of pathologists to
      reproducibly diagnose FEA and to distinguish it from CCLs without atypia has not
      been previously evaluated. Eight pathologists with an interest in breast
      pathology participated in a study to address this issue. The study reference
      pathologist provided the other seven study pathologists with a Powerpoint
      tutorial that included written criteria for, and representative images of, FEA
      and CCLs without atypia (ie, columnar cell change and columnar cell hyperplasia).
      Following review of the tutorial, the study pathologists examined images in
      Powerpoint format from 30 CCLs and were instructed to categorize each as either
      'FEA' or 'not atypical'. Overall agreement among the eight pathologists was 91.8%
      (95% CI, 84.0-96.9%), and the multi-rater kappa value was 0.83 (95% CI, 0.67
      0.94), which is within the 'excellent agreement' range. Agreement was slightly
      better for determining absence of FEA (92.8%: 95% CI, 84.1-97.4%), than for
      determining its presence (90.4%: 95% CI, 79.9-96.7%). We conclude that the
      diagnosis of FEA and its distinction from CCLs without atypia is highly
      reproducible with the use of available diagnostic criteria.

PMID- 16424890
TI  - Innate immune recognition of viral infection.
AB  - Induction of the antiviral innate immune response depends on recognition of viral
      components by host pattern-recognition receptors. Members of the Toll-like
      receptor family have emerged as key sensors that recognize viral components such
      as nucleic acids. Toll-like receptor signaling results in the production of type
      I interferon and inflammatory cytokines and leads to dendritic cell maturation
      and establishment of antiviral immunity. Cells also express cytoplasmic RNA
      helicases that function as alternative pattern-recognition receptors through
      recognition of double-stranded RNA produced during virus replication. These two
      classes of pattern-recognition receptor molecules are expressed in different
      intracellular compartments and induce type I interferon responses via distinct
      signaling pathways.

PMID- 16424893
TI  - Tissue and circulating immunoreactive protein for MMP-2 and TIMP-2 in head and
      neck squamous cell carcinoma--tissue immunoreactivity predicts aggressive
      clinical course.
AB  - Useful markers showing biological aggressiveness of head and neck squamous cell
      carcinoma (HNSCC) are needed to predict the outcome of the disease. MMP-2 is
      associated with aggressive behavior of several solid cancers. In this study, the
      clinical significance of tumor tissue and circulating immunoreactive proteins for
      MMP-2 and TIMP-2 was assessed in HNSCC. The study group consisted of 74 patients
      with HNSCC and 44 healthy controls. Expression of MMP-2 and TIMP-2 was examined
      in paraffin-embedded tumor sections by immunohistochemical methods using specific
      antibodies. The pretreatment serum levels of MMP-2, TIMP-2 and MMP-2:TIMP-2
      complex were quantitatively measured by ELISA assay. The results were compared
      with the clinicopathological factors of the disease and the patients' outcome.
      Immunohistochemical overexpression of MMP-2 in tumor was found to be prognostic
      for shortened survival in HNSCC, the 5-year cumulative relapse-free survival
      being 42% in patients with high positivity for MMP-2 in tumor vs 61% in cases
      with a negative or only weakly MMP-2-positive tumor (P=0.045). Tissue MMP-2
      positivity was also strongly connected with later lymph node or hematogenic
      relapses and associated to the cause-specific survival (P=0.055). Similarly, the
      5-year cause-specific survival was significantly poorer in patients with
      extensive positive immunostaining for tumor TIMP-2 than in those with a TIMP-2
      negative tumor (40 vs 64%, P=0.038). Patients with a TIMP-2-positive tumor also
      had an unfavorable 5-year relapse-free survival rate (43 vs 60%, respectively,
      P=0.071). Additionally, the overexpression of TIMP-2 was a powerful predictor of
      later lymph node or hematogenous metastases in HNSCC. Serum levels of MMP-2, TIMP
      2 or MMP-2:TIMP-2 complex failed to associate with the clinical behavior of HNSCC
      in this material. The results of this study provide evidence that MMP-2 and TIMP
      2 immunoreactive protein in tumor tissue of HNSCC patients, but not when assayed
      from preoperative serum samples, are prognostic in estimation of the aggressive
      clinical course of HNSCC.

PMID- 16424894
TI  - Alpha-methylacyl-CoA racemase as a marker in the differential diagnosis of
      metanephric adenoma.
AB  - Metanephric adenoma (MA), a well-described renal neoplasm, usually behaves in a
      benign fashion. It may have areas that are morphologically similar to papillary
      renal cell carcinoma (RCC) type, or epithelial (tubular predominant) type Wilms'
      tumor. Prior immunohistochemical studies of MA have reported variable staining
      patterns. Alpha-methylacyl-CoA racemase (AMACR), a molecular marker for prostate
      carcinoma, has subsequently been found to be overexpressed in breast, colorectal
      and ovarian cancers, among others. Recent microarray analysis of renal tumors has
      shown an increase of AMACR mRNA levels in papillary RCC but not in other
      subtypes. We investigated the utility of immunohistochemical staining for AMACR,
      cytokeratin 7(CK7), CD57 and WT1 to differentiate between the above-mentioned
      three neoplasms. Immunohistochemical stains were performed on paraffin-embedded
      tissue sections from 25 papillary RCC, 10 MAs and eight Wilms' tumors. AMACR was
      positive in one (10%) of 10 MAs and 24 (96%) of 25 papillary RCC, while it was
      negative in all Wilms' tumors. CK7 was positive in 20 of 25 papillary RCCs,
      focally positive in one Wilms' tumor and was negative in all MAs. CD57 was
      positive in all six MAs that were stained, focally positive in one of 25
      papillary RCC and one of eight Wilms' tumors. WT1 was positive in seven of 10
      MAs, three of 25 papillary RCCs and all eight Wilms' tumors. In conclusion,
      diffuse and strong immunoreactivity for AMACR may be useful in differentiating
      papillary RCC from MA but a panel which includes AMACR, CK7 and CD57 is better in
      this differential diagnosis. AMACR is not helpful in differentiating MA from
      Wilms' tumor, but CD57 is helpful in this differential diagnosis. WT1 may be
      useful in separating Wilms' tumor from MA and papillary RCC but is not helpful in
      differentiating MA from papillary RCC.

PMID- 16424895
TI  - pT classification, grade, and vascular invasion as prognostic indicators in
      urothelial carcinoma of the upper urinary tract.
AB  - Clinicopathologic features predictive of patient outcome in upper urinary tract
      urothelial carcinoma are not well defined. The aim of this study was to assess
      the role of pT classification, tumor grade, and vascular invasion in predicting
      metastasis-free survival. A total of 190 consecutive invasive upper urinary tract
      urothelial cancers operated between 01/1984 and 12/2004 were re-evaluated with
      respect to pT classification, tumor grade (according to the three-tiered WHO 1973
      and the recent two-tiered grading system following the WHO/ISUP consensus
      classification), as well as presence of lymph and/or blood vessel invasion.
      Prognostic impact was analyzed using the Kaplan-Meier method and the Log-Rank
      test. For multivariate testing, a Cox's proportional hazards regression model was
      used. pT1 was present in 81 (43%), pT2 in 29 (15%), pT3 in 73 (38%), and pT4 in
      seven (4%) cases. There were 12 (6%) G1, 96 (51%) G2, and 82 (43%) G3 tumors or
      84 (44%) low-grade and 106 (56%) high-grade tumors according to the two-tiered
      system. The presence of vascular invasion in 72/190 (38%) tumors was associated
      with high pT classification (P<0.001) and high tumor grade (P<0.001). Disease
      progression occurred in 39% of patients, with 5- and 10-year metastasis-free
      survival rates of 56 and 45%, respectively. On univariate analysis, all
      investigated parameters showed prognostic significance. The negative influence of
      vascular invasion on patient outcome was strikingly strong in high pT
      classification and high-grade cancers. On multivariate analysis, pT
      classification (P<0.001) and vascular invasion (P<0.001) proved to be independent
      prognostic factors, whereas tumor grade according to the two-tiered system missed
      statistical significance (P=0.06). In conclusion, pT classification and vascular
      invasion are independent prognostic factors with respect to metastasis-free
      survival and should be used to guide adjuvant therapy strategies in affected
      patients. Presence (or absence) of vascular invasion should be commented upon
      separately in the pathology report.

PMID- 16424896
TI  - Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial
      cells without lymphatic competence.
AB  - Infantile hemangiomas are common benign vascular tumors that exhibit a
      characteristic history of rapid proliferation in the first year of life and slow
      spontaneous involution during early childhood. The causative pathogenic event
      responsible for the abnormal endothelial proliferation remains elusive. The
      recent discovery of an immature phenotype of proliferating hemangioma endothelial
      cells due to the exclusive expression of the lymphatic endothelial hyaluronan
      receptor LYVE-1 led to the proposal that infantile hemangiomas are the result of
      a primary defect in endothelial cell maturation. To test this hypothesis, we
      looked for the expression of the lymphatic endothelial cell-specific markers LYVE
      1, Prox-1, podoplanin and D2-40 in beta4 integrin-negative proliferating and
      beta4 integrin-positive involuting infantile hemangiomas. As beta4 integrin
      proved to be a suitable marker for staging infantile hemangiomas, we used it in
      combination with clinical and histological criteria to objectively determine the
      proliferative and involutional phases. In immunohistochemical and
      immunofluorescent stains, hemangioma vessels were negative for all lymphatic
      endothelial cell-specific markers tested during both proliferation and
      involution. LYVE-1 immunoreactivity, however, was found in the dense network of
      perivascular HLA-DR-positive cells with dendritic cell morphology that are
      supposed to play a role in hemangiogenesis by releasing pro- and antiangiogenic
      factors. Notably, this LYVE-1 staining failed to correlate with the growth status
      of infantile hemangiomas. Our results do not support the notion that LYVE-1
      expression was restricted to the proliferative phase and downregulated during
      involution. Thus, LYVE-1 does not seem to be a reliable marker for proliferating
      infantile hemangiomas. We conclude that the suggested intrinsic defect in
      endothelial cell maturation is unlikely the cause for the post-natal rapid growth
      in infantile hemangiomas. In addition, the lack of lymphatic endothelial cell
      specific markers implies that infantile hemangiomas are tumors of blood vessels
      without lymphatic competence.

PMID- 16424897
TI  - Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in
      normal, benign and malignant breast tissue.
AB  - Nerve growth factor receptor (NGFR) is a transmembrane glycoprotein without
      intrinsic tyrosine kinase activity, whose expression is not restricted to neural
      cells. NGFR is reported to act as a tumour suppressor, negatively regulating cell
      growth and proliferation. NGFR expression was immunohistochemically analysed in
      normal breast tissue and in 140 benign, biphasic and preinvasive breast lesions,
      in 22 tumours with myoepithelial differentiation and in two cohorts of breast
      cancer patients: a series of 245 invasive breast carcinomas studied with tissue
      microarrays and 37 high-grade invasive ductal carcinomas with basal-like
      immunophenotype. NGFR consistently displayed membrane reactivity in myoepithelial
      cells arranged as a continuous layer around normal ducts and lobular units,
      intralobular fibroblasts, vascular adventitia and nerve bundles. Myoepithelial
      cells of benign proliferations and pre-invasive lesions were consistently
      positive for NGFR. Scattered NGFR-positive cells were observed in solid areas of
      six out of nine cases of hyperplasia of usual type, whereas in flat atypia,
      lobular carcinoma in situ and virtually all cases of ductal carcinoma in situ
      (97.5%), NGFR was restricted to the myoepithelial layer. Positivity for NGFR was
      observed in 11 out of 245 (4.5%) breast carcinomas, nine out of 20 (45%)
      metaplastic breast carcinomas and 14 out of 37 (38%) basal-like breast
      carcinomas. NGFR expression in invasive tumours significantly correlated with
      that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR
      (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone
      receptors (both, P<0.0001). NGFR showed a statistically significant association
      with longer disease-free (P<0.05) and overall survival (P<0.01) in the cohort of
      patients with basal-like carcinomas. This study demonstrates the usefulness of
      NGFR as a new adjunct marker to identify myoepithelial cells in preinvasive
      lesions and myoepithelial differentiation in breast carcinomas. Furthermore,
      provisional data in a small number of basal-like breast carcinomas suggest that
      NGFR may identify a subgroup of basal-like breast carcinomas with good prognosis.

PMID- 16424898
TI  - Cell-cycle-dependent Xenopus TRF1 recruitment to telomere chromatin regulated by
      Polo-like kinase.
AB  - Telomeres are regulated by a homeostatic mechanism that includes telomerase and
      telomeric repeat binding proteins, TRF1 and TRF2. Recently, it has been
      hypothesized that telomeres assume distinct configurations in a cell-cycle
      dependent manner, although direct biochemical evidence is lacking. Here we
      demonstrated that Xenopus TRF1 (xTRF1) associates with telomere chromatin
      specifically in mitotic Xenopus egg extracts, and dissociates from it upon
      mitotic exit. Both the N-terminal TRF-homology (TRFH) domain and the linker
      region connecting the TRFH domain and the C-terminal Myb domain are required for
      this cell-cycle-dependent association of xTRF1 with chromatin. In contrast,
      Xenopus TRF2 (xTRF2) associates with chromatin throughout the cell cycle. We
      showed that Polo-like kinase (Plx1) phosphorylates xTRF1 in vitro. Moreover, the
      mitotic xTRF1-chromatin association was significantly impaired when Plx1 was
      immunodepleted from the extracts. Finally, high telomerase activities were
      detected in association with replicating interphase chromatin compared with
      mitotic chromatin. These results indicate that telomere chromatin is actively
      regulated by cell-cycle-dependent processes, and provide an insight for
      understanding how telomeres undergo DNA metabolisms during the cell cycle.

PMID- 16424899
TI  - The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5
      biphosphate.
AB  - Transient receptor potential (TRP) channel, melastatin subfamily (TRPM)4 is a
      Ca2+-activated monovalent cation channel that depolarizes the plasma membrane and
      thereby modulates Ca2+ influx through Ca2+-permeable pathways. A typical feature
      of TRPM4 is its rapid desensitization to intracellular Ca2+ ([Ca2+]i). Here we
      show that phosphatidylinositol 4,5-biphosphate (PIP2) counteracts desensitization
      to [Ca2+]i in inside-out patches and rundown of TRPM4 currents in whole-cell
      patch-clamp experiments. PIP2 shifted the voltage dependence of TRPM4 activation
      towards negative potentials and increased the channel's Ca2+ sensitivity 100
      fold. Conversely, activation of the phospholipase C (PLC)-coupled M1 muscarinic
      receptor or pharmacological depletion of cellular PIP2 potently inhibited
      currents through TRPM4. Neutralization of basic residues in a C-terminal
      pleckstrin homology (PH) domain accelerated TRPM4 current desensitization and
      strongly attenuated the effect of PIP2, whereas mutations to the C-terminal TRP
      box and TRP domain had no effect on the PIP2 sensitivity. Our data demonstrate
      that PIP2 is a strong positive modulator of TRPM4, and implicate the C-terminal
      PH domain in PIP2 action. PLC-mediated PIP2 breakdown may constitute a
      physiologically important brake on TRPM4 activity.

PMID- 16424900
TI  - A rivet model for channel formation by aerolysin-like pore-forming toxins.
AB  - The bacterial toxin aerolysin kills cells by forming heptameric channels, of
      unknown structure, in the plasma membrane. Using disulfide trapping and cysteine
      scanning mutagenesis coupled to thiol-specific labeling on lipid bilayers, we
      identify a loop that lines the channel. This loop has an alternating pattern of
      charged and uncharged residues, suggesting that the transmembrane region has a
      beta-barrel configuration, as observed for Staphylococcal alpha-toxin.
      Surprisingly, we found that the turn of the beta-hairpin is composed of a stretch
      of five hydrophobic residues. We show that this hydrophobic turn drives membrane
      insertion of the developing channel and propose that, once the lipid bilayer has
      been crossed, it folds back parallel to the plane of the membrane in a rivet-like
      fashion. This rivet-like conformation was modeled and sequence alignments suggest
      that such channel riveting may operate for many other pore-forming toxins.

PMID- 16424901
TI  - Iron-responsive degradation of iron-regulatory protein 1 does not require the Fe
      S cluster.
AB  - The generally accepted role of iron-regulatory protein 1 (IRP1) in orchestrating
      the fate of iron-regulated mRNAs depends on the interconversion of its cytosolic
      aconitase and RNA-binding forms through assembly/disassembly of its Fe-S cluster,
      without altering protein abundance. Here, we show that IRP1 protein abundance can
      be iron-regulated. Modulation of IRP1 abundance by iron did not require assembly
      of the Fe-S cluster, since a mutant with all cluster-ligating cysteines mutated
      to serine underwent iron-induced protein degradation. Phosphorylation of IRP1 at
      S138 favored the RNA-binding form and promoted iron-dependent degradation.
      However, phosphorylation at S138 was not required for degradation. Further,
      degradation of an S138 phosphomimetic mutant was not blocked by mutation of
      cluster-ligating cysteines. These findings were confirmed in mouse models with
      genetic defects in cytosolic Fe-S cluster assembly/disassembly. IRP1 RNA-binding
      activity was primarily regulated by IRP1 degradation in these animals. Our
      results reveal a mechanism for regulating IRP1 action relevant to the control of
      iron homeostasis during cell proliferation, inflammation, and in response to
      diseases altering cytosolic Fe-S cluster assembly or disassembly.

PMID- 16424902
TI  - Telomere length homeostasis requires that telomerase levels are limiting.
AB  - Stabilization of telomere length in germline and highly proliferative human cells
      is required for long-term survival and for the immortal phenotype of cancer
      derived cells. This is achieved through expression of telomerase reverse
      transcriptase (TERT), which synthesizes telomeric repeats through reverse
      transcription of its tightly associated RNA template (TR). The telomeric repeat
      binding factor TRF1 inhibits telomerase at telomeres in cis in a length-dependent
      manner to achieve telomere length homeostasis. Here we manipulate telomerase
      activity over a wide range in cancer and primary cells. Concomitant
      overexpression of TERT and TR was necessary and sufficient to substantially
      increase telomerase activity. Upon overexpression, more telomerase associated
      with telomeres and telomeres elongated at a constant rate (up to 0.8
      kb/population doubling (PD)) in a length-independent manner. Thus, in less than
      50 PDs, the length of telomeres increased 3-8-fold beyond physiological size,
      while telomere-bound TRF1 and TRF2 increased proportionally to telomere length.
      Thus, long telomeres do not permanently adopt a structural state that is non
      extendible. A low cellular concentration of telomerase is critical to achieve
      preferential elongation of short telomeres and telomere length homeostasis.

PMID- 16424903
TI  - A divergent external loop confers antagonistic activity on floral regulators FT
      and TFL1.
AB  - The Arabidopsis genes FT and TERMINAL FLOWER1 (TFL1) encode related proteins with
      similarity to human Raf kinase inhibitor protein. FT, and likely also TFL1, is
      recruited to the promoters of floral genes through interaction with FD, a bZIP
      transcription factor. FT, however, induces flowering, while TFL1 represses
      flowering. Residues responsible for the opposite activities of FT and TFL1 were
      mapped by examining plants that overexpress chimeric proteins. A region important
      in vivo localizes to a 14-amino-acid segment that evolves very rapidly in TFL1
      orthologs, but is almost invariant in FT orthologs. Crystal structures show that
      this segment forms an external loop of variable conformation. The only residue
      unambiguously distinguishing the FT and TFL1 loops makes a hydrogen bond with a
      residue near the entrance of a potential ligand-binding pocket in TFL1, but not
      in FT. This pocket is contacted by a C-terminal peptide, which also contributes
      to the opposite FT and TFL1 activities. In combination, these results identify a
      molecular surface likely to be recognized by FT- and/or TFL1-specific
      interactors.

PMID- 16424904
TI  - EphB4 controls blood vascular morphogenesis during postnatal angiogenesis.
AB  - Guidance molecules have attracted interest by demonstration that they regulate
      patterning of the blood vascular system during development. However, their
      significance during postnatal angiogenesis has remained unknown. Here, we
      demonstrate that endothelial cells of human malignant brain tumors also express
      guidance molecules, such as EphB4 and its ligand ephrinB2. To study their
      function, EphB4 variants were overexpressed in blood vessels of tumor xenografts.
      Our studies revealed that EphB4 acts as a negative regulator of blood vessel
      branching and vascular network formation, switching the vascularization program
      from sprouting angiogenesis to circumferential vessel growth. In parallel, EphB4
      reduces the permeability of the tumor vascular system via activation of the
      angiopoietin-1/Tie2 system at the endothelium/pericyte interface. Furthermore,
      overexpression of EphB4 variants in blood vessels during (i) vascularization of
      non-neoplastic cell grafts and (ii) retinal vascularization revealed that these
      functions of EphB4 apply to postnatal, non-neoplastic angiogenesis in general.
      This implies that both neoplastic and non-neoplastic vascularization is driven
      not only by a vascular initiation program but also by a vascular patterning
      program mediated by guidance molecules.

PMID- 16424905
TI  - A novel ubiquitin-binding protein ZNF216 functioning in muscle atrophy.
AB  - The ubiquitin-proteasome system (UPS) is critical for specific degradation of
      cellular proteins and plays a pivotal role on protein breakdown in muscle
      atrophy. Here, we show that ZNF216 directly binds polyubiquitin chains through
      its N-terminal A20-type zinc-finger domain and associates with the 26S
      proteasome. ZNF216 was colocalized with the aggresome, which contains
      ubiquitinylated proteins and other UPS components. Expression of Znf216 was
      increased in both denervation- and fasting-induced muscle atrophy and upregulated
      by expression of constitutively active FOXO, a master regulator of muscle
      atrophy. Mice deficient in Znf216 exhibited resistance to denervation-induced
      atrophy, and ubiquitinylated proteins markedly accumulated in neurectomized
      muscle compared to wild-type mice. These data suggest that ZNF216 functions in
      protein degradation via the UPS and plays a crucial role in muscle atrophy.

PMID- 16424906
TI  - Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1.
AB  - Myogenin is required not for the initiation of myogenesis but instead for
      skeletal muscle formation through poorly understood mechanisms. We demonstrate in
      cultured cells and, for the first time, in embryonic tissue, that myogenic late
      genes that specify the skeletal muscle phenotype are bound by MyoD prior to the
      initiation of gene expression. At the onset of muscle specification, a transition
      from MyoD to myogenin occurred at late gene loci, concomitant with loss of HDAC2,
      the appearance of both the Mef2D regulator and the Brg1 chromatin-remodeling
      enzyme, and the opening of chromatin structure. We further demonstrated that
      ectopic expression of myogenin and Mef2D, in the absence of MyoD, was sufficient
      to induce muscle differentiation in a manner entirely dependent on Brg1. These
      results indicate that myogenin specifies the muscle phenotype by cooperating with
      Mef2D to recruit an ATP-dependent chromatin-remodeling enzyme that alters
      chromatin structure at regulatory sequences to promote terminal differentiation.

PMID- 16424907
TI  - The role of PACT in the RNA silencing pathway.
AB  - Small RNA-mediated gene silencing (RNA silencing) has emerged as a major
      regulatory pathway in eukaryotes. Identification of the key factors involved in
      this pathway has been a subject of rigorous investigation in recent years. In
      humans, small RNAs are generated by Dicer and assembled into the effector complex
      known as RNA-induced silencing complex (RISC) by multiple factors including
      hAgo2, the mRNA-targeting endonuclease, and TRBP (HIV-1 TAR RNA-binding protein),
      a dsRNA-binding protein that interacts with both Dicer and hAgo2. Here we
      describe an additional dsRNA-binding protein known as PACT, which is significant
      in RNA silencing. PACT is associated with an approximately 500 kDa complex that
      contains Dicer, hAgo2, and TRBP. The interaction with Dicer involves the third
      dsRNA-binding domain (dsRBD) of PACT and the N-terminal region of Dicer
      containing the helicase motif. Like TRBP, PACT is not required for the pre
      microRNA (miRNA) cleavage reaction step. However, the depletion of PACT strongly
      affects the accumulation of mature miRNA in vivo and moderately reduces the
      efficiency of small interfering RNA-induced RNA interference. Our study indicates
      that, unlike other RNase III type proteins, human Dicer may employ two different
      dsRBD-containing proteins that facilitate RISC assembly.

PMID- 16424909
TI  - Outcomes of macular hole surgery.

PMID- 16424910
TI  - Trochlear displacement by orbital plexiform neuroma: a novel mechanism causing
      superior oblique underaction.

PMID- 16424908
TI  - RuvAB is essential for replication forks reversal in certain replication mutants.
AB  - Inactivated replication forks may be reversed by the annealing of leading- and
      lagging-strand ends, resulting in the formation of a Holliday junction (HJ)
      adjacent to a DNA double-strand end. In Escherichia coli mutants deficient for
      double-strand end processing, resolution of the HJ by RuvABC leads to fork
      breakage, a reaction that we can directly quantify. Here we used the HJ-specific
      resolvase RusA to test a putative role of the RuvAB helicase in replication fork
      reversal (RFR). We show that the RuvAB complex is required for the formation of a
      RusA substrate in the polymerase III mutants dnaEts and holD, affected for the
      Pol III catalytic subunit and clamp loader, and in the helicase mutant rep. This
      finding reveals that the recombination enzyme RuvAB targets forks in vivo and we
      propose that it directly converts forks into HJs. In contrast, RFR occurs in the
      absence of RuvAB in the dnaNts mutant, affected for the processivity clamp of Pol
      III, and in the priA mutant, defective for replication restart. This suggests
      alternative pathways of RFR.

PMID- 16424912
TI  - Spontaneous hyphaema: blunt trauma and cocaine abuse.

PMID- 16424911
TI  - Expression of antiapoptotic and proapoptotic molecules in diabetic retinas.
AB  - PURPOSE: To investigate the expression of the antiapoptotic and proapoptotic
      markers in diabetic retinas. METHODS: In total, 12 donor eyes from six subjects
      with diabetes mellitus, and 10 eyes from five nondiabetic subjects without known
      ocular disease serving as control subjects were examined. Immunohistochemical
      techniques were used with antibodies directed against cyclooxygenase-2 (Cox-2),
      Akt (protein kinase B), Mcl-1, Bad, cytochrome c, apoptosis-inducing factor
      (AIF), tumour necrosis factor receptor-1-associated death domain protein (TRADD),
      and Fas-associated death domain protein (FADD). RESULTS: In retinas from all
      subjects without diabetes, cytoplasmic immunoreactivity for the antiapoptotic
      molecules Cox-2, Akt, and Mcl-1 was noted in ganglion cells. Cytoplasmic
      immunostaining for Cox-2 was also noted in the retinal pigment epithelial cells.
      Weak immunoreactivity for the mitochondrial apoptogenic proteins cytochrome c,
      and AIF was noted in the inner segments of photoreceptors, in the inner one-third
      of the outer plexiform layer, in cells in the inner nuclear layer, in the inner
      plexiform layer, and in ganglion cells. There was no immunoreactivity for the
      other antibodies tested. All diabetic retinas showed de novocytoplasmic
      immunoreactivity for Bad in ganglion cells, and in occasional cells in the inner
      nuclear layer. Upregulation of cytochrome cand AIF immunoreactivity was noted.
      Cox-2, Akt, and Mcl-1 immunoreactivity was not altered in the diabetic retinas.
      There was no immunoreactivity for TRADD, and FADD. CONCLUSIONS: Ganglion cells in
      diabetic and nondiabetic retinas express the antiapoptotic molecules Cox-2, Akt,
      and Mcl-1. Retinal ganglion cells express the proapoptotic molecule Bad in
      response to diabetes-induced neuronal injury. Diabetic retinas show upregulation
      of the mitochondrial proteins cytochrome c, and AIF.

PMID- 16424913
TI  - Mean deviation fluctuation in eyes with stable Humphrey 24-2 visual fields.
AB  - AIM: To describe the expected fluctuation in the mean deviation (MD) scores on a
      large, long-term series of stable visual field reports for particular grades of
      defect in order to give clinicians an aid to the correct diagnosis of
      glaucomatous progression. METHOD: Visual field reports of subjects with five
      reliable consecutive Humphrey 24-2 visual fields, recorded over a period of at
      least 3 years, were scored using the Advanced Glaucoma Intervention Study (AGIS)
      system. The AGIS scores of the first and last visual fields were required to be
      identical. RESULTS: A total of 202 eyes from 202 patients were used in the study,
      with a total of 1010 visual fields being used in the analysis. Visual fields with
      no defect (AGIS score 0) had a 99% confidence interval (CI) of 0.3 dB, mild
      defects 0.4 dB, moderate defects 0.8 dB, severe 1 dB, and 1.3 dB for end-stage
      defects when considering variation of MD scores. Using a one-way ANOVA
      incorporating all stages showed very little fluctuation throughout the series
      (P=0.96). The correlation between the CI and grade of field defect showed a good
      positive correlation (r=0.7, P=0.0003) indicating an increase in CI as field
      defects worsen. CONCLUSION: When considering a series of reliable visual fields
      in a stable eye, one should expect only very little fluctuation in the MD,
      indicating that an increase in the MD beyond that of the 99% CI described may
      suggest progression. The reliability indices of the visual field test should be
      regarded as a primary consideration when assessing visual fields.

PMID- 16424915
TI  - Decision-making in second-eye cataract surgery: can presence of Pulfrich
      phenomenon help?
AB  - PURPOSE: To determine whether testing for the Pulfrich phenomenon (PP) can be
      used as a tool to assess the need for and optimal timing of second-eye cataract
      surgery. METHODS: A total of 61 patients with logMAR 0 visual acuity (VA) after
      cataract surgery in one eye and logMAR 0.2-0.7 VA in the other eye were tested
      for PP using a computer-generated oscillating target at Baskent University
      Hospital. Only patients who had no ophthalmologic or systemic problem that could
      cause PP were included. In all, 15 normal patients with logMAR 0 VA in both eyes
      served as controls. The main outcome measures were presence and magnitude
      (measured by neutral density filters) of PP and presence of complaints related to
      binocular vision. RESULTS: Of the 61 patients, 36 (59%) and none of the controls
      were PP (+) (P<0.001). A total of 27 (75%) of the PP (+) patients had logMAR 0.7
      0.4 VA, and nine (25%) had logMAR 0.3-0.2 VA (P=0.01). In all, 16 patients (all
      PP (+)) had developed binocular vision-related complaints since cataract surgery.
      The mean PP magnitude in these cases was significantly greater than the mean for
      the 20 patients without complaints (1.2+/-0.5 vs0.6+/-0.4 log units,
      respectively; P<0.001). There was no significant difference between the mean VA
      in the complaint (+) and complaint (-) subgroups (P=0.213). CONCLUSION: PP
      testing may detect binocular visual dysfunction after first-eye cataract surgery;
      thus, it could help assess the need for second-eye cataract surgery on this
      basis.

PMID- 16424916
TI  - Antibody targeted drugs as cancer therapeutics.
AB  - Treatment of cancer is a double-edged sword: it should be as aggressive as
      possible to completely destroy the tumour, but it is precisely this
      aggressiveness which often causes severe side effects - a reason why some
      promising therapeutics can not be applied systemically. In addition, therapeutics
      such as cytokines that physiologically function in a para- or autocrine fashion
      require a locally enhanced level to exert their effect appropriately. An elegant
      way to accumulate therapeutic agents at the tumour site is their
      conjugation/fusion to tumour-specific antibodies. Here, we discuss recent
      preclinical and clinical data for antibody-drug conjugates and fusion proteins
      with a special focus on drug components that exert their antitumour effects
      through normal biological processes.

PMID- 16424917
TI  - Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and
      beyond.
AB  - Neuroprotective drugs tested in clinical trials, particularly those that block N
      methyl-D-aspartate-sensitive glutamate receptors (NMDARs), have failed miserably
      in large part because of intolerable side effects. However, one such drug,
      memantine, was recently approved by the European Union and the US FDA for the
      treatment of dementia following our group's discovery of its clinically tolerated
      mechanism of action. Here, we review the molecular basis for memantine efficacy
      in neurological diseases that are mediated, at least in part, by overactivation
      of NMDARs, producing excessive Ca(2+) influx through the receptor's associated
      ion channel and consequent free-radical formation.

PMID- 16424918
TI  - siRNA-based approaches in cancer therapy.
AB  - The availability of the human genome sequence has revolutionized the strategy of
      employing nucleic acids with sequences complementary to specific target genes to
      improve drug discovery and target validation. Development of sequence-specific
      DNA or RNA analogs that can block the activity of selected single-stranded
      genetic sequences offers the possibility of rational design with high
      specificity, lacking in many current drug treatments for various diseases
      including cancer, at relatively inexpensive costs. Antisense technology is one
      such example that has shown promising results and boasts of yielding the only
      approved drug to date in the genomics field. However, in vivo delivery issues
      have yet to be completely overcome for widespread clinical applications. In
      contrast to antisense oligonucleotides, the mechanism of silencing an endogenous
      gene by the introduction of a homologous double-stranded RNA (dsRNA), transgene
      or virus is called post-transcriptional gene silencing (PTGS) or RNA
      interference. PTGS is a natural mechanism whereby metazoan cells suppress
      expansion of genes when they come across dsRNA molecules with the same sequence.
      Short interfering RNA is currently the fastest growing sector of this antigene
      field for target validation and therapeutic applications. Although, in theory,
      the development of genomics-based agents to inhibit gene expression is simple and
      straightforward, the fundamental concern relies upon the capacity of the
      oligonucleotide to gain access to the target RNA. This paper summarizes the
      advances in the last decade in the field of PTGS using RNA interference
      approaches and provides relevant comparisons with other oligonucleotide-based
      approaches with a specific focus on oncology applications.

PMID- 16424919
TI  - Combined expression trait correlations and expression quantitative trait locus
      mapping.
AB  - Coordinated regulation of gene expression levels across a series of experimental
      conditions provides valuable information about the functions of correlated
      transcripts. The consideration of gene expression correlation over a time or
      tissue dimension has proved valuable in predicting gene function. Here, we
      consider correlations over a genetic dimension. In addition to identifying
      coregulated genes, the genetic dimension also supplies us with information about
      the genomic locations of putative regulatory loci. We calculated correlations
      among approximately 45,000 expression traits derived from 60 individuals in an F2
      sample segregating for obesity and diabetes. By combining the correlation results
      with linkage mapping information, we were able to identify regulatory networks,
      make functional predictions for uncharacterized genes, and characterize novel
      members of known pathways. We found evidence of coordinate regulation of 174 G
      protein-coupled receptor protein signaling pathway expression traits. Of the 174
      traits, 50 had their major LOD peak within 10 cM of a locus on Chromosome 2, and
      81 others had a secondary peak in this region. We also characterized a Riken cDNA
      clone that showed strong correlation with stearoyl-CoA desaturase 1 expression.
      Experimental validation confirmed that this clone is involved in the regulation
      of lipid metabolism. We conclude that trait correlation combined with linkage
      mapping can reveal regulatory networks that would otherwise be missed if we
      studied only mRNA traits with statistically significant linkages in this small
      cross. The combined analysis is more sensitive compared with linkage mapping
      alone.

PMID- 16424920
TI  - Plant and animal pathogen recognition receptors signal through non-RD kinases.
AB  - Plants and animals mediate early steps of the innate immune response through
      pathogen recognition receptors (PRRs). PRRs commonly associate with or contain
      members of a monophyletic group of kinases called the interleukin-1 receptor
      associated kinase (IRAK) family that include Drosophila Pelle, human IRAKs, rice
      XA21 and Arabidopsis FLS2. In mammals, PRRs can also associate with members of
      the receptor-interacting protein (RIP) kinase family, distant relatives to the
      IRAK family. Some IRAK and RIP family kinases fall into a small functional class
      of kinases termed non-RD, many of which do not autophosphorylate the activation
      loop. We surveyed the yeast, fly, worm, human, Arabidopsis, and rice kinomes
      (3,723 kinases) and found that despite the small number of non-RD kinases in
      these genomes (9%-29%), 12 of 15 kinases known or predicted to function in PRR
      signaling fall into the non-RD class. These data indicate that kinases associated
      with PRRs can largely be predicted by the lack of a single conserved residue and
      reveal new potential plant PRR subfamilies.

PMID- 16424923
TI  - Bacterial balance.

PMID- 16424921
TI  - Unusual intron conservation near tissue-regulated exons found by splicing
      microarrays.
AB  - Alternative splicing contributes to both gene regulation and protein diversity.
      To discover broad relationships between regulation of alternative splicing and
      sequence conservation, we applied a systems approach, using oligonucleotide
      microarrays designed to capture splicing information across the mouse genome. In
      a set of 22 adult tissues, we observe differential expression of RNA containing
      at least two alternative splice junctions for about 40% of the 6,216 alternative
      events we could detect. Statistical comparisons identify 171 cassette exons whose
      inclusion or skipping is different in brain relative to other tissues and another
      28 exons whose splicing is different in muscle. A subset of these exons is
      associated with unusual blocks of intron sequence whose conservation in
      vertebrates rivals that of protein-coding exons. By focusing on sets of exons
      with similar regulatory patterns, we have identified new sequence motifs
      implicated in brain and muscle splicing regulation. Of note is a motif that is
      strikingly similar to the branchpoint consensus but is located downstream of the
      5' splice site of exons included in muscle. Analysis of three paralogous membrane
      associated guanylate kinase genes reveals that each contains a paralogous tissue
      regulated exon with a similar tissue inclusion pattern. While the intron
      sequences flanking these exons remain highly conserved among mammalian orthologs,
      the paralogous flanking intron sequences have diverged considerably, suggesting
      unusually complex evolution of the regulation of alternative splicing in
      multigene families.

PMID- 16424924
TI  - Directed medication misusage.

PMID- 16424922
TI  - Colitis due to Clostridium difficile toxins: underdiagnosed, highly virulent, and
      nosocomial.
AB  - Clostridium difficile colitis is a major complication of antibiotic therapy.
      Antibiotics cause a reduction in bacteria that normally reside in the colon. If
      an antibiotic-treated patient ingests C. difficile bacteria, this organism may
      proliferate in the colon because it is resistant to most antibiotics and because
      it does not have to compete with the normal bacteria for nutrients. If the C.
      difficile organism has the gene for toxin production, the toxin can produce a
      colitis. In addition to antibiotics, other proposed risk factors for development
      of C. difficile colitis include advanced age, contact with infected patients and
      with their health care providers, impaired immune function, suppression of
      gastric acid secretion by a proton pump inhibitor, and postpyloric tube feeding.
      Many of the risk factors become simultaneously focused on patients admitted to
      the hospital. The incidence of C. difficile disease has been rising, and strains
      have become more virulent. In some forms of the disease, the patient doesn't have
      diarrhea, and in such patients C. difficile can be deadly but difficult to
      diagnose. The standard treatment, with metronidazole or vancomycin, fails to work
      in up to 25% of patients with the fulminant form of colitis. Since C. difficile
      causes only 20% of cases of antibiotic-associated diarrhea, a specific test is
      needed to diagnose this organism. Toxigenic cultureis highly specific but not
      available at most institutions. The tests that are available--enzyme-linked
      immunosorbent assay and fecal cytotoxicity assay--have high false-negative rates,
      even in patients with severe clinical disease, creating a diagnostic dilemma. The
      only proven way to reduce the risk of C. difficile disease is implementation of
      an antibiotic management program in conjunction with enhanced infection control
      procedures.

PMID- 16424926
TI  - Crossing the species barrier: the threat of an avian influenza pandemic.
AB  - Avian influenza (H5N1) has recently been recognized as a new emerging infectious
      disease that may pose a threat to international public health. Most recent
      developments lead to the belief that H5N1 could become the cause of the next
      influenza pandemic. This review discusses the characteristics of H5N1 avian
      influenza virus as an emerging infectious disease with the potential for pandemic
      development. In addition, the current pandemic influenza alert status and
      guidelines for pandemic preparedness, treatment, and prevention are discussed.

PMID- 16424925
TI  - Laboratory testing considerations for C. difficile disease.

PMID- 16424927
TI  - Medicare modernization: the new prescription drug benefit and redesigned Part B
      and Part C.
AB  - The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 was
      enacted in November 2003 and became effective on January 1, 2006. Two major
      changes occurred. A prescription drug benefit is now available for seniors and
      younger persons with disabilities who are covered by Medicare. The managed care
      program, formerly known as Medicare + Choice, has been redesigned and renamed
      Medicare Advantage.

PMID- 16424928
TI  - John Snow, MD: anaesthetist to the Queen of England and pioneer epidemiologist.

PMID- 16424929
TI  - Jay Donald Mabrey, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 16424930
TI  - Acute-onset cervical spine pain and neurologic deficit in a previously healthy
      young woman.

PMID- 16424931
TI  - Fever and malaise associated with a painful papule on the ankle.

PMID- 16424932
TI  - Angina pectoris, dyspnea, fatigue, and edema after a non-ST-segment-elevation
      myocardial infarct.

PMID- 16424934
TI  - Giving depositions as a defendant or an expert.

PMID- 16424933
TI  - Eszopiclone (Lunesta): a new nonbenzodiazepine hypnotic agent.
AB  - Randomized, placebo-controlled trials have shown that eszopiclone, a newly
      available nonbenzodiazepine hypnotic, effectively treats the symptoms of
      insomnia. Its pharmacokinetic and pharmacodynamic parameters are similar to those
      of the other currently available nonbenzodiazepine hypnotics (i.e., zolpidem and
      zaleplon). The unique quality of eszopiclone lies in its product labeling. It is
      not restricted to short-term use, unlike both zolpidem and zaleplon. Dosing of
      eszopiclone should begin at 2 mg for nonelderly patients and may be initiated at
      or increased to 3 mg if clinically indicated. The 3-mg nightly dose is more
      effective at sleep maintenance. Eszopiclone is well tolerated, with the main
      treatment-emergent side effects being unpleasant taste, headache, and dizziness.
      No studies comparing eszopiclone with nonpharmacologic insomnia treatments or
      other hypnotic agents, including zolpidem and zaleplon, are currently available.

PMID- 16424935
TI  - Would you want to be a patient in your office?

PMID- 16424936
TI  - A doctor's message from Katrina's front lines.

PMID- 16424937
TI  - Facts and ideas from anywhere.

PMID- 16424938
TI  - Selective generation of functional somatically mutated IgM+CD27+, but not Ig
      isotype-switched, memory B cells in X-linked lymphoproliferative disease.
AB  - Individuals with X-linked lymphoproliferative disease (XLP) display defects in B
      cell differentiation in vivo. Specifically, XLP patients do not generate a normal
      number of CD27 memory B cells, and those few that are present are IgM. Recent
      studies have suggested that IgMCD27 B cells are not true memory cells, but rather
      B cells that guard against T cell-independent pathogens. Here we show that human
      XLP IgMCD27 B cells resemble normal memory B cells both morphologically and
      phenotypically. Additionally, IgMCD27 B cells exhibited functional
      characteristics of normal memory B cells, including the ability to secrete more
      Ig than naive B cells in response to both T cell-dependent and -independent
      stimuli. Analysis of spleens from XLP patients revealed a paucity of germinal
      centers (GCs), and the rare GCs detected were poorly formed. Despite this, Ig
      variable region genes expressed by XLP IgMCD27 B cells had undergone somatic
      hypermutation to an extent comparable to that of normal memory B cells. These
      findings reveal a differential requirement for the generation of IgM and Ig
      isotype-switched memory B cells, with the latter only being generated by fully
      formed GCs. Production of affinity-matured IgM by IgMCD27 B cells may protect
      against pathogens to which a normal immune response is elicited in XLP patients.

PMID- 16424939
TI  - Peptide vaccination of mice immune to LCMV or vaccinia virus causes serious CD8 T
      cell-mediated, TNF-dependent immunopathology.
AB  - CD8 T cells play a key role in clearing primary virus infections and in
      protecting against subsequent challenge. The potent antiviral effects of these
      cells make them important components of vaccine-induced immunity and, because of
      this, peptide vaccines often contain epitopes designed to induce strong CD8 T
      cell responses. However, the same effector functions that protect the host also
      can be harmful if they are not tightly regulated, and virus-specific CD8 T cells
      are a frequent cause of immunopathology. Here, we report that the administration
      of peptide to virus-immune recipient mice can lead to the synchronous activation
      of preexisting virus-specific CD8 T cells with serious, and even lethal,
      consequences. Mice infected with LCMV or vaccinia virus developed rapid and
      profound hypothermia following injection of cognate synthetic peptides, and LCMV
      infected mice frequently died within hours. Detailed analyses of the LCMV
      infected mice revealed enterocyte apoptosis and implicated TNF produced by
      peptide-specific CD8 T cells as the major mediator of disease. The caspase
      inhibitor zVADfmk had no demonstrable effect on the development of hypothermia,
      but diminished enterocyte apoptosis and greatly reduced the number of deaths.
      These findings, if similarly observed in patients, counsel caution when
      administering powerful immunogens such as peptide vaccines to individuals who may
      have a large preexisting pool of epitope-specific CD8 T cells.

PMID- 16424943
TI  - From the editor. The Desired Sensation Level (DSL) method for fitting hearing
      aids.

PMID- 16424941
TI  - c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and
      synthesis of new analogs.
AB  - Although active vitamin D drugs have been used for the treatment of osteoporosis,
      how the vitamin D receptor (VDR) regulates bone cell function remains largely
      unknown. Using osteoprotegerin-deficient mice, which exhibit severe osteoporosis
      due to excessive receptor activator of NF-kappaB ligand/receptor activator of NF
      kappaB (RANKL/RANK) stimulation, we show herein that oral treatment of these mice
      with 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] inhibited bone resorption
      and prevented bone loss, suggesting that VDR counters RANKL/RANK signaling. In M
      CSF-dependent osteoclast precursor cells isolated from mouse bone marrow,
      1alpha,25(OH)2D3 potently and dose-dependently inhibited their differentiation
      into multinucleate osteoclasts induced by RANKL. Among signaling molecules
      downstream of RANK, 1alpha,25(OH)2D3 inhibited the induction of c-Fos protein
      after RANKL stimulation, and retroviral expression of c-Fos protein abrogated the
      suppressive effect of 1alpha,25(OH)2D3 on osteoclast development. By screening
      vitamin D analogs based on their c-Fos-suppressing activity, we identified a new
      analog, named DD281, that inhibited bone resorption and prevented bone loss in
      ovariectomized mice, more potently than 1alpha,25(OH)2D3, with similar levels of
      calcium absorption. Thus, c-Fos protein is an important target of the skeletal
      action of VDR-based drugs, and DD281 is a bone-selective analog that may be
      useful for the treatment of bone diseases with excessive osteoclastic activity.

PMID- 16424940
TI  - Toll-like receptor 2 controls expansion and function of regulatory T cells.
AB  - Tregs play a central role in the suppression of immune reactions and prevention
      of autoimmune responses harmful to the host. During acute infection, however,
      Tregs might hinder effector T cell activity directed toward the elimination of
      the pathogenic challenge. Pathogen recognition receptors from the TLR family
      expressed by innate immune cells are crucial for the generation of effective
      immunity. We have recently shown the CD4CD25 Treg subset in TLR2 mice to be
      significantly reduced in number compared with WT littermate control mice,
      indicating a link between Tregs and TLR2. Here, we report that the TLR2 ligand
      Pam3Cys, but not LPS (TLR4) or CpG (TLR9), directly acts on purified Tregs in a
      MyD88-dependent fashion. Moreover, when combined with TCR stimulation, TLR2
      triggering augmented Treg proliferation in vitro and in vivo and resulted in a
      temporal loss of the suppressive Treg phenotype in vitro by directly affecting
      Tregs. Importantly, WT Tregs adoptively transferred into TLR2 mice were
      neutralized by systemic administration of TLR2 ligand during the acute phase of a
      Candida albicans infection, resulting in a 100-fold reduced C. albicans
      outgrowth. This demonstrates that in vivo TLR2 also controls the function of
      Tregs and establishes a direct link between TLRs and the control of immune
      responses through Tregs.

PMID- 16424942
TI  - Tlx acts as a proangiogenic switch by regulating extracellular assembly of
      fibronectin matrices in retinal astrocytes.
AB  - In response to hypoxia, hypoxia-inducible factors act as the primary
      proangiogenic triggers by regulating transcription levels of target genes,
      including VEGF. However, little is known about the specific factors that control
      other components of the angiogenic process, particularly formation of matrix
      scaffolds that promote adhesion and migration of endothelial cells. We show that
      in the postnatal mouse retina, the orphan nuclear receptor tailless (Tlx) is
      strongly expressed in the proangiogenic astrocytes, which secrete VEGF and
      fibronectin. Tlx expression by retinal astrocytes is controlled by oxygen
      concentration and rapidly downregulated upon contact with blood vessels. In mice
      null for Tlx, retinal astrocytes maintain VEGF expression; however, the
      extracellular assembly of fibronectin matrices by astrocytes is severely
      impaired, leading to defective scaffold formation and a complete failure of
      normal retinal vascular development. This work identifies Tlx as an essential
      component of the molecular network involved in the hypoxia-inducible
      proangiogenic switch in retinal astrocytes.

PMID- 16424944
TI  - The DSL method for pediatric hearing instrument fitting: historical perspective
      and current issues.
AB  - The Desired Sensation Level (DSL) Method was originally developed in the early
      1980s to provide clinicians with a systematic, science-based approach to
      pediatric hearing instrument fitting that ensures audibility of amplified speech
      by accounting for factors that are uniquely associated with the provision of
      amplification to infants and young children who have hearing loss. This review
      identifies and describes several of the primary factors that have been considered
      in the development of the DSL Method. Specifically, the issues discussed relate
      to: (1) the definition and measurement of relevant acoustic, electroacoustic and
      audiometric variables; (2) how the external ear acoustics of infants and young
      children are accounted for in the DSL Method for both audiometric assessment and
      in the fitting of amplification; and (3) how the DSL Method has evolved
      concurrently with developments in hearing instrument and electroacoustic
      measurement technologies. Finally, current issues in the field are identified
      that have motivated the development of version 5.0 of the DSL Method for hearing
      instrument fitting.

PMID- 16424947
TI  - Surgery in rural America.
AB  - Despite recent increased attention to ailing health-care systems in rural
      America, policy makers have paid relatively little attention to the status of
      rural surgery. This paucity of attention is rooted in a combination of poor
      communication and incomplete knowledge. Unfortunately, the scarce dialogue
      between advocates of rural surgery and policy makers has been driven largely by
      anecdotes and generalizations. What is needed as a foundation for productive
      discourse is evidence-based objective observations regarding important issues and
      concerns related to rural surgical practice. This article reviews our current
      understanding of several of these issues; namely, the adequacy of the current and
      future surgical workforce, preparation for rural practice, professional
      isolation, rural surgical quality, and the critical interplay between rural
      surgeons and local systems of care in which they function. The intent of this
      article is to stimulate further inquiry that will create a foundation for
      meaningful dialogue between rural surgeons, surgical leaders, and health-care
      policy makers.

PMID- 16424946
TI  - Clinical protocols for hearing instrument fitting in the Desired Sensation Level
      method.
AB  - A discussion of the protocols used particularly in the clinical application of
      the Desired Sensation Level (DSL) Method is presented in this chapter. In the
      first section, the measurement and application of acoustic transforms is
      described in terms of their importance in the assessment phase of the
      amplification fitting process. Specifically, the implications of individual ear
      canal acoustics and their impact on accurately defining hearing thresholds are
      discussed. Detailed information about the statistical strength of the real-ear-to
      coupler difference (RECD) measurement and how to obtain the measure in young
      infants is also provided. In addition, the findings of a study that examined the
      relationship between behavioral and electrophysiologic thresholds in real-ear SPL
      is described. The second section presents information related to the
      electroacoustic verification of hearing instruments. The RECD is discussed in
      relation to its application in simulated measurements of real-ear hearing
      instrument performance. In particular, the effects of the transducer and coupling
      method during the RECD measurement are described in terms of their impact on
      verification measures. The topics of insertion gain, test signals, and venting
      are also considered. The third section presents three summary tables that outline
      the hearing instrument fitting process for infants, children, and adults.
      Overall, this chapter provides both clinical and scientific information about
      procedures used in the assessment and verification stages of the DSL Method.

PMID- 16424945
TI  - The Desired Sensation Level multistage input/output algorithm.
AB  - The Desired Sensation Level (DSL) Method was revised to support hearing
      instrument fitting for infants, young children, and adults who use modern hearing
      instrument technologies, including multichannel compression, expansion, and
      multimemory capability. The aims of this revision are to maintain aspects of the
      previous versions of the DSL Method that have been supported by research, while
      extending the method to account for adult-child differences in preference and
      listening requirements. The goals of this version (5.0) include avoiding loudness
      discomfort, selecting a frequency response that meets audibility requirements,
      choosing compression characteristics that appropriately match technology to the
      user's needs, and accommodating the overall prescription to meet individual needs
      for use in various listening environments. This review summarizes the status of
      research on the use of the DSL Method with pediatric and adult populations and
      presents a series of revisions that have been made during the generation of DSL
      v5.0. This article concludes with case examples that illustrate key differences
      between the DSL v4.1 and DSL v5.0 prescriptions.

PMID- 16424948
TI  - Innovation by committee? Reigniting surgical robotics research and development.

PMID- 16424949
TI  - "Instrumental from the Start'': George Berci, MD, FACS, FRCS, ED (Hon).

PMID- 16424950
TI  - Clinical presentation and surgical outcome in patients with solitary rectal ulcer
      syndrome.
AB  - Solitary rectal ulcer syndrome is a poorly understood clinical condition, and the
      schema of treatment has not yet been defined. This study reviewed the clinical
      spectra and outcome of various surgical treatments in patients with solitary
      rectal ulcer syndrome. The medical records of all patients with solitary rectal
      ulcer syndrome between 1992 and 1998 were retrospectively reviewed. Patients in
      the study population with symptoms and histopathologic findings suggestive of
      solitary rectal ulcer syndrome were placed in the primary solitary rectal ulcer
      syndrome group, and patients who underwent surgery for other diseases in whom
      histopathology confirmed concomitant solitary rectal ulcer syndrome were in the
      incidental group. Clinical features and outcomes of surgical treatment were
      documented. Improvement was considered as resolution of presenting symptoms, and
      non-improvement was considered if presenting symptoms persisted or worsened. The
      study cohort comprised 49 patients: 20 in the primary group and 29 in the
      incidental group. Ulcerative morphology was seen predominantly in the primary
      group (70%); erythematous (45%) and polypoid lesions (34%) were predominant in
      the incidental group (P = .0025). Clinical improvement after surgery was seen in
      74% of patients with primary and 79% with incidental solitary rectal ulcer
      syndrome (P = NS). Manifestations such as tenesmus and digitation correlated with
      poorer outcome after surgery in both groups. Solitary rectal ulcer syndrome is a
      clinical condition associated with functional anorectal evacuatory disorders. The
      results of this study show the positive role of surgical treatment for underlying
      functional disorders in the improvement of incidental solitary rectal ulcer
      syndrome.

PMID- 16424951
TI  - Efficacy of novel robotic camera vs a standard laparoscopic camera.
AB  - To improve visualization during minimal access surgery, a novel robotic camera
      has been developed. The prototype camera is totally insertable, has 5 degrees of
      freedom, and is remotely controlled. This study compared the performance of
      laparoscopic surgeons using both a laparoscope and the robotic camera. The
      MISTELS (McGill Inanimate System for the Training and Evaluation of Laparoscopic
      Skill) tasks were used to test six laparoscopic fellows and attending surgeons.
      Half the surgeons used the laparoscope first and half used the robotic camera
      first. Total scores from the MISTELS sessions in which the laparoscope was used
      were compared with the sessions in which the robotic camera was used and then
      analyzed with a paired t test (P < .05 was considered significant). All six
      surgeons tested showed no significant difference in their MISTELS task
      performance on the robotic camera compared with the standard laparoscopic camera.
      The mean MISTELS score of 963 for all subjects who used a laparoscope and camera
      was not significantly different than the mean score of 904 for the robotic camera
      (P = .17). This new robotic camera prototype allows for equivalent performance on
      a validated laparoscopic assessment tool when compared with performance using a
      standard laparoscope.

PMID- 16424952
TI  - Significant reduction of laparotomy-associated lung metastases and subcutaneous
      tumors after perioperative immunomodulation with flt3 ligand in mice.
AB  - Laparotomy has been associated with increased rates of tumor establishment and
      metastasis formation postoperatively in animal models. The purpose of this study
      was to determine the impact on postoperative tumor growth of perioperative
      upregulation of immune function via fetal liver tyrosine kinase 3 (Flt3 ligand).
      Two murine studies were carried out: the first utilized a lung metastases model,
      and the second involved a subcutaneous tumor model. Each study included four
      groups: anesthesia control (AC), AC plus Flt3 ligand (ACFlt3), sham laparotomy
      (OP), and OP plus Flt3 ligand (OPFlt3). Flt3 ligand was administered by daily
      intraperitoneal injection (10 mug/dose) beginning 5 days preoperatively and
      continuing for 1 week postoperatively. In study 1, A/J mice were given tail vein
      injections of 1.5 x 10(5) TA3Ha cancer cells on the day of surgery. The mice were
      sacrificed 14 days after surgery, the lungs processed, and the surface metastases
      counted by a blinded observer. In study 2 C3H/He mice were given a dorsal
      subcutaneous injection of 10(4) MC-2 cancer cells on the day of surgery. The mice
      were sacrificed 31 days after surgery, and the injection sites were evaluated for
      subcutaneous tumors grossly and histologically. In study 1, the median number of
      surface lung metastases per mouse was 166 in the OP group and 38 in the OPFlt3 (P
      = .021). Mice in the AC group developed a median 50 lung metastases per animal
      compared with mice in the ACFlt3 group who had a median of 10 metastases per
      mouse (P = .001). The OP group had significantly more metastases than the AC
      group (P = .048). In study 2, the percentage of animals that developed tumors in
      the AC, OP, ACFlt3, and OPFlt3 groups was 43, 80, 0, and 20, respectively. The
      incidence of tumors in the OPFLt3 group and the ACFlt3 group was significantly
      less than their respective control groups (P < .01). The difference between the
      OP and AC groups was not significant (P > .05). Perioperatively administered Flt3
      ligand was associated with significantly fewer lung metastases and a lower
      incidence of subcutaneous tumor formation after laparotomy and anesthesia alone.
      Perioperative immunomodulation may limit untoward surgery-related oncologic
      effects.

PMID- 16424954
TI  - Rapid increase in serum levels of matrix metalloproteinase-9 (MMP-9)
      postoperatively is associated with a decrease in the amount of intracellular MMP
      9.
AB  - We have previously demonstrated a significant decrease in the serum concentration
      of intact insulin-like growth factor-binding protein (IGFBP-3) after laparotomy.
      IGFBP-3, a major IGF binding protein, inhibits the growth of tumor cells via
      several mechanisms. Our goal was to determine, in a murine model, whether matrix
      metalloproteinase-9 (MMP-9), a known protease of IGFBP-3, is responsible for the
      postoperative decrease in serum IGFBP-3 levels. Six IGFBP-3 transgenic mice on a
      CD-1 background were used in this study. These mice over-express human IGFBP-3.
      Sham laparotomy, in the form of a midline abdominal incision, was the test
      procedure. General anesthesia was established using ketamine and xylazine
      immediately before a 30-minute sham laparotomy and before preoperative blood
      sampling, done via retro-orbital venipuncture, 48 hours before surgery. The
      animals were sacrificed and blood was drawn 24 hours postoperatively. Plasma MMP
      9 activity was measured using zymography at each time point (48 hours before and
      24 hours after operation). MMP-9 activity was also measured in mononuclear cell
      lysates at both time points. Zymography analysis demonstrated significantly
      higher plasma levels of MMP-9 postoperatively compared with preoperative levels
      (81 RU vs 40 RU; P < .05). In contrast, mononuclear cell levels of MMP-9 were
      significantly higher preoperatively compared with postoperative levels (37.5 RU
      vs. 0.75 RU, P < .05). Plasma levels of MMP-9, a known protease of IGFBP-3, are
      significantly elevated postoperatively. In addition, mononuclear cells that store
      MMP-9 are depleted of it postoperatively. This suggests that rapid MMP-9 release
      by mononuclear cells leads to an increase in serum levels of this protease
      postoperatively. Further studies will elucidate mechanisms of MMP-9-related IGFBP
      3 depletion.

PMID- 16424953
TI  - Telementoring: an important enabling tool for the community surgeon.
AB  - This study evaluated the efficacy of telementoring as an enabling tool for
      community general surgeons to perform advanced laparoscopic surgical procedures.
      We present a series of 19 patients who underwent advanced laparoscopic surgical
      procedures in two community hospitals, between November 2002 and July 2003, by
      four community surgeons with no formal advanced laparoscopic training. Each
      surgeon was telementored by an expert surgeon from a tertiary care hospital.
      Telementoring was achieved with real-time two-way audio-video communications over
      Internet Protocol or Integrated Services Digital Network lines with bandwidths
      from 385 kbps to 1.2 mbps. The procedures included 10 bowel resections, 5 Nissen
      fundoplications, 2 splenectomies, 1 reversal of a Hartmann procedure, and 1
      ventral hernia repair. Two of the 19 procedures (11%) were converted to open.
      There were no intraoperative complications and two postoperative complications
      (11%). The primary surgeon considered telementoring useful in all cases (median
      score, 4 of 5). The mentor was also comfortable with the quality of the
      laparoscopic surgery performed (median score, 4 of 5). Telecommunication
      bandwidth for audio and video transmission was found to be a critical factor in
      the quality of telementoring process. Telementoring is safe and feasible. It
      allows community surgeons with no formal advanced laparoscopic training to
      benefit from expert intraoperative advice during the performance of advanced
      laparoscopic procedures. It may also reduce health-care costs by avoiding the
      need to refer and transfer patients to tertiary care centers.

PMID- 16424955
TI  - Energy sources for laparoscopic colectomy: a prospective randomized comparison of
      conventional electrosurgery, bipolar computer-controlled electrosurgery and
      ultrasonic dissection. Operative outcome and costs analysis.
AB  - The development of operative laparoscopic surgery is linked to advances in
      ancillary surgical instrumentation. Ultrasonic energy devices avoid the use of
      electricity and provide effective control of small- to medium-sized vessels.
      Bipolar computer-controlled electrosurgical technology eliminates the
      disadvantages of electrical energy, and a mechanical blade adds a cutting action.
      This instrument can provide effective hemostasis of large vessels up to 7 mm.
      Such devices significantly increase the cost of laparoscopic procedures, however,
      and the amount of evidence-based information on this topic is surprisingly
      scarce. This study compared the effectiveness of three different energy sources
      on the laparoscopic performance of a left colectomy. The trial included 38
      nonselected patients with a disease of the colon requiring an elective segmental
      left-sided colon resection. Patients were preoperatively randomized into three
      groups. Group I had electrosurgery; vascular dissection was performed entirely
      with an electrosurgery generator, and vessels were controlled with clips. Group
      II underwent computer-controlled bipolar electrosurgery; vascular and mesocolon
      section was completed by using the 10-mm Ligasure device alone. In group III, 5
      mm ultrasonic shears (Harmonic Scalpel) were used for bowel dissection, vascular
      pedicle dissection, and mesocolon transection. The mesenteric vessel pedicle was
      controlled with an endostapler. Demographics (age, sex, body mass index,
      comorbidity, previous surgery and diagnoses requiring surgery) were recorded, as
      were surgical details (operative time, conversion, blood loss), additional
      disposable instruments (number of trocars, EndoGIA charges, and clip appliers),
      and clinical outcome. Intraoperative economic costs were also evaluated. End
      points of the trial were operative time and intraoperative blood loss, and an
      intention-to-treat principle was followed. The three groups were well matched for
      demographic and pathologic features. Surgical time was significantly longer in
      patients operated on with conventional electrosurgery vs the Harmonic Scalpel or
      computed-based bipolar energy devices. This finding correlated with a significant
      reduction in intraoperative blood loss. Conversion to other endoscopic techniques
      was more frequent in Group I; however, conversion to open surgery was similar in
      all three groups. No intraoperative accident related to the use of the specific
      device was observed in any group. Immediate outcome was similar in the three
      groups, without differences in morbidity, mortality, or hospital stay. Analysis
      of operative costs showed no significant differences between the three groups.
      High-energy power sources specifically adapted for endoscopic surgery reduce
      operative time and blood loss and may be considered cost-effective when left
      colectomy is used as a model.

PMID- 16424957
TI  - Computing support for information-rich laparoscopy.
AB  - Developments in the architecture and organization of high-performance general
      purpose computer systems are largely ignored by the technology infrastructure of
      the modern laparoscopic surgical suite. The current state of technology for
      laparoscopy is a camera and monitor linked via a controller that distributes
      analog or digital video signals without regard to their content. This article
      discusses the opportunities that will be created by inserting general-purpose
      high-performance computing into the information stream between camera and
      display. We envision that the use of this technology will radically transform
      laparoscopy from its current state as ;;surgery by pictures'' into an entirely
      new, information-rich surgical environment.

PMID- 16424956
TI  - The Steinberg-Bernstein Centre for Minimally Invasive Surgery at McGill
      University.
AB  - Surgical skills and simulation centers have been developed in recent years to
      meet the educational needs of practicing surgeons, residents, and students. The
      rapid pace of innovation in surgical procedures and technology, as well as the
      overarching desire to enhance patient safety, have driven the development of
      simulation technology and new paradigms for surgical education. McGill University
      has implemented an innovative approach to surgical education in the field of
      minimally invasive surgery. The goal is to measure surgical performance in the
      operating room using practical, reliable, and valid metrics, which allow the
      educational needs of the learner to be established and enable feedback and
      performance to be tracked over time. The GOALS system and the MISTELS program
      have been developed to measure operative performance and minimally invasive
      surgical technical skills in the inanimate skills lab, respectively. The MISTELS
      laparoscopic simulation-training program has been incorporated as the manual
      skills education and evaluation component of the Fundamentals of Laparoscopic
      Surgery program distributed by the Society of American Gastrointestinal and
      Endoscopic Surgeons (SAGES) and the American College of Surgeons.

PMID- 16424958
TI  - A marketing-oriented perspective on physician selection.
AB  - The process of selecting a physician is an inherently difficult one for patients.
      Physician selection is often made from limited information, and in many cases,
      the information used as the basis for physician selection is obtained indirectly
      through either medical service providers or other consumers or patients. When
      selecting a physician, patients tend to rely on personal sources of information
      and place importance on the reputational aspects of the health-care provider,
      organization, and experience. Patient expectations for the technical aspects of
      the health-care experience are stringent and must be met or exceeded by
      physicians and other health-care providers to compete long-term in the health
      care market place. Beyond this, health-care providers can favorably influence
      patient perceptions of the health-care experience by excelling at the functional
      aspects of service provision (ie, the interpersonal- and process-oriented
      attributes). This article examines the physician selection process and provides
      marketing-oriented recommendations for addressing some of the challenges patients
      encounter when selecting a physician.

PMID- 16424959
TI  - Health care as a fixed-cost industry: implications for delivery.
AB  - Most health-care costs are fixed and sunk. Fixed costs do not vary with the level
      of patient activity, and once sunk they cannot be easily reversed. We must
      rethink how we manage the expensive investments in our health care
      infrastructure, which is where most costs lie. The conventional approaches to
      rationing care have failed. Physicians have been told to lower the cost of care
      by rationing resources. This rationing includes reducing the length of patients'
      hospital stays but this does not work as intended. A new paradigm advocates
      making more and better use of existing assets and by pursuing improvements
      incrementally and at the bedside. Elements include flexing intensive care unit
      beds, improving operating room efficiencies, and rationalizing health care
      capacity.

PMID- 16424960
TI  - Pouch perineal rectosigmoidectomy: a case report.
AB  - Many surgical methods have been described for the treatment of full-thickness
      rectal prolapse. Rarely, unusually large lengths of colon must be excised, thus
      resulting in a significant loss of the absorptive function of the remaining
      colon. We present an unusual case in which an extraordinary length of the colon
      was excised and a perineal reservoir was created in the form of a colonic J-pouch
      to improve continence.

PMID- 16424961
TI  - Do (we) surgeons need a "makeover''?

PMID- 16424962
TI  - Prognostic value of parent-adolescent disagreement in a referred sample.
AB  - OBJECTIVE: To investigate whether parent-adolescent disagreement regarding
      reports on adolescents' psychopathology indicates a poor prognosis. METHODS: A
      total of 151 11- to 18-year-olds who had been assessed with the Child Behavior
      Checklist (CBCL) and Youth Self-Report (YSR) at referral to an outpatient
      psychiatry clinic were followed up. At follow-up, 4.3 years later, signs of poor
      outcome were assessed. FINDINGS: Discrepancies between CBCL and YSR scores
      predicted future disciplinary problems at school, police/judicial contacts, and
      drug use. CONCLUSIONS: To determine the prognosis of psychopathology in
      adolescents who are referred to mental health services, discrepancies between
      parents and adolescents may be useful. Given the relatively large number of
      statistical comparisons (n = 16) that was needed to obtain these results, future
      studies are needed to test if the results are robust across different settings.

PMID- 16424963
TI  - Adults' self-efficacy beliefs and referral attitudes for boys and girls with
      AD/HD.
AB  - Males with Attention Deficit/Hyperactivity Disorder (AD/HD) are referred to
      specialists significantly more frequently than females. The aim of this study was
      to examine differences in mothers' and prospective educators' self-efficacy
      beliefs and severity perceptions towards boys and girls with AD/HD and to explore
      the inter-relationships between those perceptions and referral judgements. One
      hundred and fifteen female prospective preschool educators and 118 mothers of
      boys and girls aged 4-6, enrolled in kindergartens in Athens completed a
      questionnaire that: (a) presented a vignette describing a typical boy or girl
      with AD/HD, and (b) was followed by two scales exploring severity perceptions and
      self-efficacy beliefs with reference to the child described in the vignette.
      Mothers' sense of self-efficacy was higher than educators' and both samples had
      higher sense of self-efficacy towards girls with AD/HD than boys. Educators rated
      the boys' behaviour as significantly more severe than girls'. Finally, perceived
      self-efficacy predicted severity perceptions and severity perceptions predicted
      referral decisions. To conclude, adults' differentiated perceptions of severity
      of AD/HD in boys and girls, which might be influenced by their own limited self
      efficacy beliefs, especially towards males, might account for a proportion of the
      differences in referral ratio of boys and girls with AD/HD.

PMID- 16424964
TI  - Preferences of the public regarding cutbacks in expenditure for patient care: are
      there indications of discrimination against those with mental disorders?
AB  - BACKGROUND: Increasing costs for patient care may necessitate financial cuts in
      the health-care budget. Our aim is to examine whether the public prefers cuts for
      psychiatric rather than medical conditions and how resource allocation
      preferences are related to illness beliefs and attitudes. METHOD: A telephone
      survey involving German adult population was conducted in 2004 (n = 1012).
      Participants were presented with a list of nine medical and mental diseases
      including alcoholism, depression, schizophrenia, Alzheimer's disease, cancer,
      diabetes, rheumatism and AIDS, and were asked to name three conditions where they
      would prefer to see health-care resources cut. For all conditions we asked about
      personal attitudes and illness beliefs. RESULTS: People were more willing to have
      financial resources cut for psychiatric than for medical conditions, with
      resources for alcoholism having the least public backing. Alzheimer's disease was
      rated more favourably compared to other mental disorders. Generally, the
      perception of the severity of a disease was associated with resource allocation
      decisions, favouring those conditions that were considered to be severe. Mental
      diseases evoked a far greater desire for social distance than most medical
      diseases which had considerable influence on resource allocation preferences. The
      perception of personal responsibility had, in contrast, only limited effect on
      resource allocation decisions. It varied considerably in the case of psychiatric
      conditions but was not fundamentally different among medical and mental diseases.
      Personal susceptibility, treatment effectiveness and the perceived life-threat
      posed by a disease also had limited effects. CONCLUSION: According to public
      resource allocation preferences psychiatric patients are at risk of being
      structurally discriminated within the health-care system.

PMID- 16424966
TI  - Influence of newspaper reporting on adolescents' attitudes toward people with
      mental illness.
AB  - BACKGROUND: Numerous studies have established proof of selective media reporting
      about the mentally ill, with the majority of the reports focusing almost
      exclusively on violence and dangerousness. A handful of studies found that there
      is an association between negative media portrayals and negative attitudes toward
      people with mental illness. However, empirical evidence of the impact of
      newspaper reports about mentally ill people on readers' attitudes is very scarce.
      AIMS: To examine the impact of a newspaper article linking mentally ill persons
      with violent crime and the impact of an article providing factual information
      about schizophrenia on students' attitudes toward people with mental illness.
      METHOD: A total of 167 students aged 13-18 years were randomly assigned one of
      two articles. A period of 1 week before and 3 weeks after reading the newspaper
      article, they were asked to complete a self-administered questionnaire for the
      assessment of their attitudes toward mentally ill people. RESULTS: Respondents
      who read the article linking mentally ill persons with violent crime displayed an
      increased likelihood to describe a mentally ill person as dangerous and violent.
      Conversely, respondents who read the informative article used terms like
      'violent' or 'dangerous' less frequently. The desire for social distance remained
      virtually unchanged at follow-up in both groups. CONCLUSION: Two potential
      approaches to break the unwanted link between negative media reporting and
      negative attitudes are suggested. First, an appeal to media professionals to
      report accurate representations of mental illness. And second, an appeal to the
      adults living and working with adolescents to provide opportunities to discuss
      and reflect on media contents.

PMID- 16424967
TI  - Differences in perceived coercion at admission to psychiatric hospitals in the
      Nordic countries.
AB  - BACKGROUND: International variation in compulsory admissions to psychiatric care
      has mainly been studied in terms of civil commitment rates. The objectives of
      this study were to compare and analyse the levels of perceived coercion at
      admission to psychiatric in-patient care among the Nordic countries and between
      centres within these countries, in relation to legal prerequisites and clinical
      practice. METHOD: From one to four centres each in Denmark, Iceland, Norway,
      Finland and Sweden, a total of 426 legally committed and 494 formally voluntarily
      admitted patients were interviewed within 5 days from admission. RESULTS: The
      proportion of committed patients reporting high levels of perceived coercion
      varied among countries (from 49% in Norway to 100% in Iceland), and in Sweden,
      only, among centres (from 29 to 90%). No clear variations in this respect were
      found among voluntary patients. A wide concept of coercion in the Civil
      Commitment Act and no legal possibility of detention of voluntary patients were
      associated to low levels of perceived coercion at admission among committed
      patients. CONCLUSION: For committed patients, differences in national legal
      prerequisites among countries were reflected in differences in perceived
      coercion. The results from Sweden also indicate that local care traditions may
      account for variation among centres within countries.

PMID- 16424965
TI  - Adolescents referred to specialty mental health care from local services and
      adolescents who remain in local treatment: what differs?
AB  - BACKGROUND: The study investigates whether adolescents referred to specialty
      mental health services from local services differ from adolescents who only have
      received help for psychiatric problems locally. If so, which factors associate
      strongest with referral? METHOD: Adolescents (n = 76) from an adolescent
      population sample (N = 2,538) who had received help during the last year for
      mental problems from local services were compared to a clinical sample of
      adolescents (N = 129) referred to specialty mental health services from such
      local services. Comparisons were made according to scores on the Youth Self
      Report (YSR); depressive symptoms; family functioning; attachment to parents;
      self-concept; coping styles; response styles; dysfunctional attitudes; negative
      life events; daily hassles; socio-demographics. RESULTS: As compared to
      adolescents receiving help locally, adolescents in specialty mental health care
      scored higher on YSR internalising syndrome; YSR attention problems; YSR thought
      problems; suicidality; psychosocial stressors; knowing someone who had attempted
      suicide; parental divorce; substance use; recent moves; living in lodgings; lost
      a pal or boy/girlfriend; and lower on attachment to parents. Multivariate
      logistic regression analysis identified four factors associated with receiving
      specialty mental health care: low family functioning; moved previous year;
      knowing someone who had attempted suicide; own suicidality. CONCLUSIONS: Family
      functioning as reported by the adolescents, and not mental health problems except
      for suicidality, was found to be the strongest associated with referral to
      specialty mental health services. Contrary to findings from many other studies,
      referral was associated with internalising problems, not externalising ones.

PMID- 16424968
TI  - Was there unmet mental health need after the September 11, 2001 terrorist
      attacks?
AB  - BACKGROUND: This study examined the use of professionals for mental health
      problems among New York City residents who were directly affected by the
      September 11, 2001 terrorist attacks on the World Trade Center (WTC) or had a
      probable diagnosis of post-traumatic stress disorder (PTSD) or depression in its
      aftermath. Correlates of help seeking from professionals for mental health
      problems after the attacks and barriers to care were also assessed. METHOD: Data
      were from a random digit dial telephone survey of 2,752 adults representative of
      the Greater New York Metropolitan area conducted 6 months after the September 11
      terrorist attacks. RESULTS: Fifteen percent of those directly affected and 36% of
      those with probable PTSD or depression sought help from a professional for a
      mental health problem after the attacks. There was little new utilization of
      professionals for mental health problems after the attacks among persons who were
      not already receiving care prior to September 11. Barriers that prevented people
      from seeking help for mental health problems 6 months after the September 11
      attacks included traditional barriers to care (e.g., cost) and barriers that are
      unique to the post-disaster context (e.g., the belief that others need the
      services more than oneself). CONCLUSIONS: This study suggests that there was
      potential unmet mental health need in New York City 6 months after the September
      11 attacks on the WTC, but these findings should be tempered by research showing
      an apparent decrease in population-rates of PTSD. In the aftermath of a disaster,
      interventions should target persons with mental health needs who were not
      previously seeking help from a professional for a mental health problem.

PMID- 16424969
TI  - Demand-oriented care: the development and validation of a measuring instrument.
AB  - OBJECTIVES: Demand-oriented care has recently become a key topic in the area of
      care provision, fitting into the modern pursuit for patient autonomy. This paper
      introduces a measuring instrument to assess demand-orientation in mental health
      care. METHOD: A concept mapping procedure was used to understand the concept of
      demand-orientation. The resulting items were introduced to a validating sample of
      204 patients of three mental health facilities. After factor analysis, a 19-item
      General-Demand Orientated Care Questionnaire (DOC-G), and a supplementary
      questionnaire (DOC-S) containing 6 sections remained. This questionnaire was
      submitted to confirmatory analysis in a random sample (n = 304) of psychiatric
      patients. RESULTS: Respondents were predominantly female (57.6%), of Dutch ethnic
      origin (84.1%), and outpatients (71.4%). The analyses confirmed the 4-factor
      structure of the questionnaire. Both internal and external validity of the
      instrument proved to be sufficient. The questionnaire discriminated in the
      experience of demand-orientation of care between patients who did and those who
      did not have a treatment plan put up; between those who did and those who did not
      have a crisis plan, and between those who had a lifetime prevalence of undergoing
      compulsory treatment, and those who had not. CONCLUSIONS: We conclude that the
      DOC is a useful instrument to measure demand-orientation in a population of
      psychiatric patients. It is useful to measure changes in care quality. The
      supplementary questionnaires make it possible to evaluate chosen projects or
      subprojects quickly.

PMID- 16424971
TI  - Patterns of inpatient care for immigrants in Switzerland: a case control study.
AB  - BACKGROUND: Migration has become a major political and social concern in West
      European societies. METHODS: A case-control method was used to analyse the
      utilisation of inpatient mental health services by immigrants from a catchment
      area in Switzerland over a 7-year period. RESULTS: Compared to natives,
      immigrants had fewer psychiatric hospitalisations, but more emergency and
      compulsory admissions. During inpatient treatment, they received less psycho-,
      ergo- and physiotherapy. Other therapies as well as compulsory measures were at
      comparable rates, as was the frequency of irregular discharge. They spent shorter
      periods as inpatients and the rate of psychiatric readmissions was significantly
      lower. Comparison of different countries of origin revealed that only patients
      from West and North Europe were comparable to natives regarding type of referral,
      inpatient treatment, and longitudinal measures of service utilisation. Even after
      accounting for effects of social class, immigrants from South Europe, former
      Yugoslavia, Turkey, East Europe and more distant countries spent significantly
      shorter time in inpatient treatment, compared to Swiss control patients.
      CONCLUSIONS: Results of this study clearly point to an underutilisation of
      inpatient facilities among immigrants with mental disorders, and to disadvantages
      in psychiatric inpatient care. This, however, does not pertain to all foreign
      patients to the same extent: inequalities of mental health service use are
      particularly pronounced in immigrants from more distant countries.

PMID- 16424972
TI  - Comparative study of clinical characteristics of neutropenic and non-neutropenic
      adult cancer patients with bloodstream infections.
AB  - A total of 399 consecutive episodes of bloodstream infections in adult patients
      with haematologic malignancies and solid tumours were evaluated prospectively
      over a 26-month period, with the aim of determining the clinical characteristics
      and the microbiological profile of the patients relative to neutrophil count. The
      overall 30-day mortality rate was 32% (35% in non-neutropenic patients vs. 26% in
      neutropenic patients, p=0.05). Main diagnoses were solid tumours (33%) and
      lymphoma (29%). Most of the episodes of bloodstream infection (58%) occurred in
      non-neutropenic patients. Acute leukaemia and bone marrow transplantation
      predominated in the neutropenic group. Non-neutropenic patients tended to be
      older and to have a higher frequency of solid tumours and advanced or
      uncontrolled diseases. Indwelling central venous catheters were present in 51% of
      the episodes, with a predominance of long-term catheters in neutropenic
      haematologic patients. Concomitant infections were observed more frequently in
      non-neutropenic patients. There were 1,040 noninfectious comorbid conditions,
      most of which were present in non-neutropenic patients. The causative pathogens
      were predominantly gram-negative bacilli (56%). Escherichia coli and Klebsiella
      pneumoniae were isolated more frequently from neutropenic patients, while
      Staphylococcus aureus and Acinetobacter spp. were more frequent in non
      neutropenic patients. Seventy-four percent of the episodes of candidaemia
      occurred in patients with central venous catheters, with non-albicans strains
      predominating. The results of this study highlight the heterogeneity of cancer
      patients with bloodstream infections and the value of stratifying risk factors
      and aetiologic agents according to neutrophil count.

PMID- 16424970
TI  - Feasibility of mental health screening and intervention in the HUNT population
      study.
AB  - BACKGROUND: The aim of the current study was to investigate feasibility,
      response, and consequences of mental health screening and intervention in a
      population study setting. METHODS: In the Intervention study against Depression
      and Anxiety in Nord-Trondelag (IDANT), all GPs and psychiatric nurses were
      invited to a psychiatric educational programme prior to the Health Study of Nord
      Trondelag County, Norway (HUNT 2, 1995-1997). Included in the HUNT 2 was the
      Hospital Anxiety and Depression rating Scale (HADS). All participants scoring 25
      points or above (99th percentile, n = 654) were defined as the Psychiatric High
      Risk Group, (PHRG) and received a written notification regarding their high
      scores with a request to see their GP and to participate in the IDANT. RESULTS:
      In total 422 (64%) baseline forms could be retrieved in the IDANT. However, only
      177 (27%) were returned by the GPs. Three out of four participants in the PHRG
      were already recognised by their GPs as patients with mental disorders prior to
      the IDANT. Negative reactions to the notification letter or to the invitation to
      the IDANT were uncommon, still only half of the subjects in the PHRG participated
      in the study. However, as a consequence of the IDANT in 64% of the cases the GPs
      started new treatment, revised ongoing treatment, or referred the respondents.
      CONCLUSIONS: Though attitude towards psychiatry among GPs and participants was
      generally positive, response to the IDANT study was inadequate. Relatively few
      new cases were detected, yet the results indicate that the GPs altered their
      psychiatric care and practice markedly within the PHRG. Whether the educational
      programme had an impact on psychiatric services in the county in general cannot
      be answered in this study.

PMID- 16424974
TI  - Comparative evaluation of a new Vitek 2 system for identification and
      antimicrobial susceptibility testing of Streptococcus pneumoniae.

PMID- 16424973
TI  - Usefulness of teicoplanin for preventing methicillin-resistant Staphylococcus
      aureus infections in orthopedic surgery.
AB  - In order to gather more data on the use of teicoplanin for reducing MRSA
      infections in high-risk populations, the present study was conducted. At a
      hospital in Barcelona, Spain, there was a high prevalence of MRSA infections
      among patients who underwent surgery for femoral neck fracture during the first 5
      months of 2002 (period A) when cefuroxime was the antibiotic prophylaxis. During
      the following 12 months (period B) 600 mg of teicoplanin was added to cefuroxime.
      The rates of overall and MRSA infection during period A were 5.07 and 2.73%,
      respectively. Pulsed-field gel electrophoresis demonstrated there was no clonal
      relationship among MRSA strains. No nasal carriers of MRSA were detected among
      health workers. During period B the rates of overall and MRSA infection were 2.36
      and 0.19%, respectively. Both rates were statistically significantly lower than
      those in period A (p<0.05). These results suggest teicoplanin may be useful in
      patients undergoing orthopedic surgery when the prevalence of MRSA is high.

PMID- 16424975
TI  - Recurrent Rhodococcus equi infection with fatal outcome in an immunocompetent
      patient.
AB  - The majority of human Rhodococcus equi infections occur in immunocompromised
      hosts, especially those with AIDS, and infection in immunocompetent patients is
      rare. Reported here is a case of R. equi infection in a seemingly healthy patient
      with a very complicated course. Despite neurosurgery and prolonged antibiotic
      therapy the patient deceased.

PMID- 16424976
TI  - Prenatal alcohol exposure (PAE) reduces the size of the forepaw representation in
      forepaw barrel subfield (FBS) cortex in neonatal rats: relationship between
      periphery and central representation.
AB  - Prenatal alcohol exposure (PAE) alters limb development that may lead to
      structural and functional abnormalities of the limb reported in children
      diagnosed with Fetal Alcohol Spectrum Disorder. To determine whether PAE alters
      the central representation of the forelimb we used the rodent barrel cortex as
      our model system where it was possible to visualize and quantitatively measure
      the size of the forepaw representation in the forepaw barrel subfield (FBS) in
      first somatosensory cortex. In the present study, we examined the effects of PAE
      on pattern and size of the forepaw and forepaw representation in FBS in neonatal
      rats at gestational day 32 that corresponds to postnatal day 9. Pregnant Sprague
      Dawley rats were chronically intubated with binge doses of ethanol (6 g/kg) from
      gestational day 1 through gestational day 20. The offspring of the ethanol
      treated dams comprised the ethanol (EtOH) group. The effect of PAE on the EtOH
      group was compared with a nutritional-controlled pairfed (PF) group and a normal
      chowfed (CF) group. The ventral (glabrous) surface area of the forepaw digits,
      length of digit 2 through digit 5, and the corresponding glabrous forepaw digit
      representations in the FBS were measured and compared between treatment groups.
      In rats exposed to in utero alcohol, the sizes of the overall glabrous forepaw
      and forepaw digits were significantly reduced in EtOH pups compared to CF and PF
      pups; overall glabrous forepaw area was 11% smaller than CF controls. Glabrous
      digit lengths were also smaller in EtOH rats compared to CF controls and
      significantly smaller in digit 2 through digit 4. The glabrous digit
      representation in FBS was 18% smaller in the EtOH group when compared to the CF
      treatment. However, PAE did not produce malformations in the forepaw or alter the
      pattern of the forepaw representation in FBS; instead, PAE significantly reduced
      both body and brain weights compared to controls. Unexpectedly, little or no
      correlation was observed between the size of the glabrous forepaw compared to the
      size of the glabrous forepaw representation in the FBS for any of the treatment
      groups. The present findings of PAE-related alterations in sensory periphery and
      the central cortical representation may underlie deficits in sensorimotor
      integration reported among children with Fetal Alcohol Spectrum Disorder.

PMID- 16424977
TI  - Corticomotor excitability during a choice-hand reaction time task.
AB  - Fourteen neurologically healthy, right-handed subjects performed a choice-hand
      reaction time (RT) task, which involved wrist flexion or extension of either the
      left or right hand to one of three fixed target locations corresponding to 45
      degrees flexion, 20 degrees flexion, or 20 degrees extension from the starting
      position. In each trial, a pre-cue provided information regarding the forthcoming
      target location. The hand was specified by the imperative signal. Focal
      transcranial magnetic stimulation (TMS) was delivered over the hand motor area of
      either the right or left hemisphere at set times during the foreperiod, and at
      random intervals during the RT interval defined by electromyography onset. As
      expected, an increase in corticomotor excitability was observed in the agonist of
      the responding hand over the RT interval. When the cue appeared at a location
      that required flexion with either hand, an increase in excitability was observed
      following stimulation over the hemisphere ipsilateral to the responding hand,
      indicating activation of the homologous muscle. However, when the cue appeared at
      a location at which the response would require flexion with one hand and
      extension with the other, the modulation of excitability was also based on the
      direction of the response. This direction-specific effect was only observed for
      TMS delivered to the left hemisphere during the left-hand movement, and suggested
      goal-based preparation in the left hemisphere independent of whether the actual
      movement is made with the right or left hand. These results indicate that both
      the homologous-muscle and the directional-specific constraints affect the
      corticomotor excitability of the non-responding hand.

PMID- 16424978
TI  - Adaptation to visual feedback delays in manual tracking: evidence against the
      Smith Predictor model of human visually guided action.
AB  - We report adaptation to delayed visual feedback during a manual tracking task,
      testing the nature of the adapted responses with frequency analysis. Two groups
      of seven subjects tracked unpredictable targets using a handheld joystick,
      alternating between pursuit and compensatory display trials. The test group then
      practised for 1 h per day with a visual feedback delay of 300 ms; the control
      group practice under normal undelayed conditions. Introduction of the visual
      feedback delay significantly disrupted tracking performance, with an increase in
      errors and a reduction in frequency of corrective movements. Subjects showed
      clear evidence of adaptation during the 5 day experiment, decreasing tracking
      error and decreasing the mean power of intermittent corrections. However, there
      was no evidence of a return towards the initial high frequency intermittent
      tracking. We suggest that the adaptation observed in this study reflects the
      modification of predictive feedforward actions, but that these data do not
      support control based on Smith Prediction.

PMID- 16424979
TI  - Polymorphism in the 3'-untranslated region of the thymidylate synthase gene and
      sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy.
AB  - To investigate the relationship between polymorphism in the 3'-untranslated
      region (3'-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric
      cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric
      cancer were analyzed. All patients were treated with 5-FU-based chemotherapy; DNA
      from peripheral blood leukocytes was obtained before therapy. TS 3'-UTR genotypes
      were detected by PCR-RFLP. Polymorphism in the TS 3'-UTR can be classified into
      three groups according to the presence or absence of a 6 bp nucleotide fragment:
      the -6/-6 bp, -6/+6 bp and +6/+6 bp groups. The response rate of the -6/-6 bp and
      -6/+6 bp groups was found to be significantly higher than the +6/+6 bp group.
      These results show that the presence of the TS 3'-UTR 6 bp nucleotide fragment
      can be correlated with the sensitivity of gastric cancer to 5-FU-based
      chemotherapy, and that the TS 3'-UTR polymorphism profile can be used to guide
      the choice of 5-FU-based chemotherapy in advanced gastric cancer.

PMID- 16424980
TI  - Macrophage inflammatory protein-2 promotes angiogenesis, cell migration, and
      tumor growth in hepatic metastasis.
AB  - BACKGROUND: In a mouse model of hepatic metastasis, we herein analyzed whether
      the CXC chemokine macrophage inflammatory protein (MIP)-2, a functional analogue
      of the human interleukin 8, stimulates tumor cell migration in vitro and
      angiogenesis and tumor growth in vivo. METHODS: By using chemotaxis chambers,
      CT26.WT colorectal tumor cell adhesion and migration were studied under
      stimulation with different concentrations of MIP-2. To evaluate angiogenesis and
      tumor growth in vivo, 1 x 10(5) CT26.WT cells were implanted into the left liver
      lobe of syngeneic BALB/c mice, and 10, 100, and 1000 nM of MIP-2 or phosphate
      buffered saline (controls) was injected into the peritumoral area. After 7 days,
      angiogenesis, proliferation, tumor growth, apoptosis, cleaved caspase 3, and CXCR
      2 expression were analyzed by using intravital fluorescence microscopy,
      histology, immunohistochemistry, and fluorescence-activated cell sorting.
      RESULTS: In vitro, 98.8% of unstimulated CT26.WT cells showed CXCR-2 receptor
      expression. In the chemotaxis assays, MIP-2 provoked a dose-dependent increase of
      cell migration and a most pronounced cell adhesion at a dose of 100 nM. In vivo,
      MIP-2, in particular in a dose of 100 or 1000 nM, induced a significant increase
      of tumor capillary density and a marked widening of the angiogenic front at the
      tumor margin. Capillaries of the angiogenic front, but not of the tumor center,
      showed significant dilation, thus indicating a pronounced action of vascular
      endothelial growth factor. Tumor volume was significantly increased, in
      particular after 100 nM of MIP-2 stimulation, when compared with phosphate
      buffered saline-treated controls, whereas only 1000 nM of MIP-2-treated animals
      additionally showed a higher frequency of apoptotic cell death within the tumor
      margin. CONCLUSIONS: Our study indicates for the first time that the CXC
      chemokine MIP-2 promotes angiogenesis and growth of colorectal CT26.WT hepatic
      metastasis.

PMID- 16424981
TI  - The role of genetic markers--NAP1L1, MAGE-D2, and MTA1--in defining small
      intestinal carcinoid neoplasia.
AB  - BACKGROUND: Standard clinical and immunohistochemical methods cannot reliably
      determine whether a small intestinal carcinoid (SIC) is indolent or aggressive.
      We hypothesized that carcinoid malignancy could be defined by using quantitative
      reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemical
      approaches that evaluate potential marker genes. METHODS: Candidate marker gene
      expression (nucleosome assembly protein 1-like 1 [NAP1L1], melanoma antigen D2
      [MAGE-D2], and metastasis-associated protein 1 [MTA1]) identified by Affymetrix
      transcriptional profiling was examined by QRT-PCR in SIC, liver, and lymph node
      (LN) metastases, colorectal carcinomas, and healthy tissues. Immunohistochemical
      expression levels of MTA1 were analyzed quantitatively by a novel automated
      quantitative analysis in a tissue microarray of 102 gastrointestinal carcinoids
      and in a breast/prostate carcinoma array. RESULTS: Affymetrix transcriptional
      profiling identified three potentially useful malignancy-marker genes (out of
      1709 significantly altered genes). By QRT-PCR, NAP1L1 was significantly (P < .03)
      overexpressed in SIC compared with colorectal carcinomas and healthy tissue.
      Increased levels (P < .05) were identified in both liver and LN metastases.
      Levels in colorectal carcinomas were the same as in healthy mucosa. MAGE-D2 and
      MTA1 were increased (P < .05) in primary tumors and metastases and overexpressed
      in carcinomas. Automated quantitative analysis demonstrated the highest levels of
      MTA1 immunostaining in malignant primary SICs and in metastases to the liver and
      LN. These were significantly increased (P < .02) compared with nonmetastatic
      primary tumors. MTA1 was overexpressed in breast and prostate carcinomas (P <
      .05). CONCLUSIONS: SICs overexpress the neoplasia-related genes NAP1L1 (mitotic
      regulation), MAGE-D2 (adhesion), and MTA1 (estrogen antagonism). The ability to
      determine the malignant potential of these tumors and their propensity to
      metastasize provides a biological rationale for the management of carcinoids and
      may have prognostic utility.

PMID- 16424982
TI  - Synergistic effect of interstitial laser coagulation and doxorubicin in a murine
      tumor recurrence model of solitary colorectal liver metastasis.
AB  - BACKGROUND: Interstitial laser coagulation (ILC) is gaining acceptance for
      treatment of unresectable colorectal liver metastases. However, local recurrence
      rates are still high. To overcome this problem, we investigated the potential of
      additional systemic therapy after ILC in a murine model. METHODS: Single C26
      colon carcinoma nodules (approximately 1 mm3) expressing firefly luciferase were
      implanted in the left liver lobe of 32 BALB/c mice. Seven days after
      implantation, tumors were treated with either ILC alone (neodymium-yttrium
      aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin
      intravenously. Controls received either doxorubicin alone or sham treatment.
      Tumor load was measured by in vivo bioluminescent imaging. RESULTS: Solitary
      colorectal liver metastases developed over 7 days after tumor implantation in the
      liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the
      liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After
      ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0
      of 14). Sham treatment or treatment with doxorubicin alone showed an exponential
      increase in tumor load. CONCLUSIONS: A murine tumor recurrence model after local
      ablative treatment of solitary liver metastasis was developed. The combination of
      ILC and doxorubicin had a strong synergistic effect that led to complete tumor
      remission in all animals treated.

PMID- 16424983
TI  - Laparoscopic lateral pancreaticojejunostomy: a new remedy for an old ailment.
AB  - BACKGROUND: Lateral pancreaticojejunostomy is considered as the standard surgery
      for chronic pancreatitis. Yet there are very few reports of this procedure being
      done laparoscopically. We present our experience with laparoscopic lateral
      pancreaticojejunostomy till date and describe our technique. MATERIAL AND METHOD:
      Since 1997, we have done 12 laparoscopic lateral pancreatojejunostomies. There
      were 9 females and 3 males and the average age was 29.3 years. The indication for
      surgery in all patients was intractable abdominal pain and significant weight
      loss. Additionally, two patients were also suffering from pancreatic ascites.
      RESULTS: The average diameter of the pancreatic duct was 14.7 mm. We used a four
      port technique. All surgeries were completed without any conversion to open
      surgery. Post-operatively, there were no major morbidity and nil mortality. The
      average operating time was 172 minutes. Post-operative stay was short (average 5
      days) and on median follow-up of 4.4 years, 83.3% patients had complete pain
      relief while 16.7% had partial relief. All patients had significant weight gain.
      CONCLUSIONS: Laparoscopic lateral pancreaticojejunostomy is safe, effective and
      feasible in experience hands. Mastery of intracorporeal knotting and suturing
      techniques is mandatory before embarking on this surgery.

PMID- 16424984
TI  - Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and
      laparoscopic antireflux surgery.
AB  - BACKGROUND: Laparoscopy has become the standard surgical approach to both surgery
      for gastroesophageal reflux disease and large/paraesophageal hiatal hernia repair
      with excellent long-term results and high patient satisfaction. However, several
      studies have shown that laparoscopic hiatal hernia repair is associated with high
      recurrence rates. Therefore, some authors recommend the use of prosthetic meshes
      for either laparoscopic large hiatal hernia repair or laparoscopic antireflux
      surgery. The aim of this article was to review available studies regarding the
      evolution, different techniques, results, and future perspectives concerning the
      use of prosthetic materials for closure of the esophageal hiatus. METHODS: A
      search of electronic databases, including Medline and Embase, was performed to
      identify available articles regarding prosthetic hiatal closure for large hiatal
      or paraesophageal hernia repair and/or laparoscopic antireflux surgery.
      Techniques and results as well as recurrence rates and complications related to
      the use of prosthetics for hiatal closure were reviewed and compared.
      Additionally, recent experiences and recommendations of experienced experts in
      this field were collected. RESULTS: The results of 42 studies were analyzed in
      this review. Some techniques of mesh hiatal closure were evaluated; however, most
      authors prefer posterior mesh cruroplasty. The type and shape of hiatal meshes
      vary from small angular meshes to A-shaped, V-shaped, or complete circular
      meshes. The most frequently utilized materials are polypropylene,
      polytetrafluoroethylene, or dual meshes. All studies show a low rate of
      postoperative hernia recurrence, with no mortality and low morbidity. In
      particular, comparative studies including two prospective randomized trials
      comparing simple sutured hiatal closure to prosthetic hiatal closure show a
      significantly lower rate of postoperative hiatal hernia recurrence and/or
      intrathoracic wrap migration in patients who underwent prosthetic hiatal closure.
      CONCLUSIONS: Laparoscopic large hiatal/paraesophageal hernia repair with
      prosthetic meshes as well as laparoscopic antireflux surgery with prosthetic
      hiatal closure are safe and effective procedures to prevent hiatal hernia
      recurrence and/or postoperative intrathoracic wrap migration, with low
      complication rates. The type of mesh, particularly the size and shape, is still
      controversial and is a matter for future research in this field.

PMID- 16424985
TI  - Health-related quality-of-life changes after laparoscopic and open incisional
      hernia repair: a matched pair analysis.
AB  - BACKGROUND: The objective of this matched control study in patients suffering
      from incisional hernia was to compare laparoscopic open repair (LHR) with open
      hernia repair (OHR) in terms of long-term health-related quality of life (HRQL)
      according to the SF-36 Health Survey. METHODS: Twenty-four consecutive patients
      (18 male, six female; mean age, 55 years) prospectively underwent LHR using
      expanded polytetrafluoroethylene mesh. The second group, which was matched for
      age and gender, was subjected to OHR using large pore-sized, low-weight
      polypropylene meshes. Before and after surgery, HRQL was assessed by the SF-36
      Health Survey, which measures eight different health-quality domains, and the SF
      36 Physical (PCS) and Mental Component Summary (MCS) score. The SF-36 values were
      compared to the scores of age-stratified German population controls. RESULTS: The
      patients were reevaluated 16 months (range, 12-25) after LHR and 28 months
      (range, 18-52) after OHR, respectively. Before surgery, all of the eight health
      quality domains as well as the PCS and MCS scores of both study groups were
      significantly lower than the corresponding scores of the age-stratified healthy
      German population. However, the OHR patients had significantly higher physical
      functioning and vitality scores than the LHR patients. After LHR and OHR, the
      scores for all eight SF-36 domains significantly increased but were still lower
      than those of the controls. The LHR patients were still worse than the norm
      population on both PCS and MCS scores, whereas OHR patients were worse only on
      PCS but not on MCS. In the long-term follow-up, none of the SF-36 Health Survey
      domains or the PCS and the MCS scores revealed significant differences between
      LHR and OHR patients. CONCLUSIONS: LHR was not different from OHR for selected
      indications that measure long-term outcome and HRQL. SF-36 appears to be an
      appropriate instrument to measure postoperative HRQL, showing responsiveness to
      changes in objective outcome measures.

PMID- 16424986
TI  - Fibrin glue for securing the mesh in laparoscopic totally extraperitoneal
      inguinal hernia repair: a study with a 40-month prospective follow-up period.
AB  - BACKGROUND: Anchoring the mesh in laparoscopic totally extraperitoneal groin
      hernia repair (TEP) with human fibrin glue has theoretical advantages. However,
      these have been supported and reported previously only in animal studies. Before
      the initiation of large patient trials, the authors wanted to confirm the
      feasibility, assess the costs, and rule out any flagrant short- and long-term
      adverse effects of fibrin glue usage in a small series of patients. METHODS: Nine
      consecutive TEP repairs with fibrin glue mesh fixation were performed. The
      perioperative and postoperative outcomes at 1, 16, and 40 months were compared
      with those for a control group of 96 stapled repairs. RESULTS: Gluing was easy
      and is less expensive than stapling. No fibrin glue-related adverse effects were
      found. The overall outcome was similar to that for stapled repairs, with no
      indication that the glued repairs were inferior. CONCLUSIONS: Fibrin glue seems
      to be a reasonable, feasible, and maybe even competitive alternative to the
      standard tissue-penetrating mesh fixation. The results of this study justify
      launching larger trials.

PMID- 16424987
TI  - Use of the laparoscopic-endoscopic approach, the so-called "rendezvous"
      technique, in cholecystocholedocholithiasis: a valid method in cases with patient
      related risk factors for post-ERCP pancreatitis.
AB  - BACKGROUND: Several studies have shown the efficacy and effectiveness of the
      combined endoscopic-laparoscopic "rendezvous" technique for treatment of
      gallbladder and bile duct stones without complications, particularly
      pancreatitis. The so-called rendezvous technique consists of laparoscopic
      cholecystectomy standards with intraoperative cholangiography followed by
      endoscopic sphincterotomy (EST). The sphincterotome is driven across the papilla
      through a guidewire inserted by the transcystic route. This method allows easier
      and faster cannulation, thus avoiding papillary edema and pancreatic trauma. The
      aim of this study was to evaluate whether this method is effective in eliminating
      ductal stones and to verify whether the risk of postprocedure pancreatitis is
      diminished. METHODS: From January 2002 to September 2004, we enrolled 256
      patients with cholecystocholedolithiasis detected by transabdominal ultrasound
      and magnetic resonance cholangiopancreatography. One hundred and twenty of these
      had one or more patient-related risk factors for post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis, so they were randomized into two
      groups of 60 patients. In group A, the patients were treated in a single step
      with videolaparoscopic cholecystectomy, intraoperative cholangiography, and EST
      during the surgical procedure with the rendezvous technique. In group B,
      preoperative ERCP and EST were performed by using a traditional method of bile
      duct cannulation. RESULTS: No cases of post-ERCP pancreatitis were observed in
      group A, whereas six cases of acute post-ERCP pancreatitis occurred in group B
      (five mild and one moderate) (p = 0.0274). No procedure-related mortality was
      recorded. CONCLUSION: In cholecysthocholedocholithiasis, the combined
      laparoscopic-endoscopic approach prevents post-ERCP pancreatitis in cases with
      patient-related risk factors for this complication.

PMID- 16424988
TI  - Endoscopic treatment of pancreatic pseudocysts.
AB  - BACKGROUND: This study aimed to assess the effectiveness of therapeutic endoscopy
      in the treatment of pancreatic pseudocysts, and to define factors limiting
      endoscopic therapy. METHODS: The results of therapeutic endoscopy were evaluated
      for 170 patients with pancreatic pseudocysts treated at the Department of
      Surgery, Helsinki University Central Hospital, during the 6-year period from 1998
      to 2003. RESULTS: The therapeutic endoscopy success rate was 86.1%, with 23
      (13.9%) patients requiring operative treatment because therapeutic endoscopy was
      unsuccessful or technically impossible. There was little morbidity and no
      procedure-related mortality. The majority of the 38 complications, which arose
      from 380 procedures, could be treated conservatively. CONCLUSIONS: Endoscopic
      methods are safe and effective for the treatment of pancreatic pseudocysts. The
      indications for surgery include inaccessible pancreatic duct, location, or
      content of the pseudocyst rendering the problem not amenable to endoscopic
      therapy, as well as complications of the endoscopic treatment.

PMID- 16424990
TI  - Cost-effective laparoscopic appendicectomy [corrected].

PMID- 16424989
TI  - Linear stapling of the short gastric vessels reduces blood loss and splenectomy
      at oesophageal and gastric surgery.
AB  - BACKGROUND: Increased operative blood loss, blood transfusion and nontherapeutic
      splenectomy negatively influence postoperative morbidity and mortality following
      esophageal or gastric resection. A critical point at which blood loss and
      iatrogenic splenic injury occurs is at the time of division of the short gastric
      vessels. We examined the efficacy of using a laparoscopic linear cutting stapler
      (developed for minimal access surgery) to divide with the short gastric vessels
      at open surgery. METHODS: Fifty-six patients were included. In 28 consecutive
      patients the linear stapler was used when dividing the short gastric vessels.
      These were compared to 28 matched controls (short gastric vessels were divided
      between hemostats and ligated). In the two patient groups, patient age, body mass
      index, and preoperative hemoglobin levels were similar. RESULTS: Operation time,
      splenectomy rates, blood transfusion, and mean transfusion volume were all
      significantly reduced in the group where the stapler was used. CONCLUSION: Use of
      a linear cutting stapler reduced operation time, blood product use, and
      incidental splenectomy in patients undergoing radical open esophageal and gastric
      surgery.

PMID- 16424991
TI  - Evaluation of target scores and benchmarks for the traversal task scenario of the
      Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR) laparoscopy
      simulator.
AB  - BACKGROUND: The Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR)
      simulator is validated for laparoscopy training, but benchmarks and target scores
      for assessing single tasks are needed. METHODS: Control data for the MIST-VR
      traversal task scenario were collected from 61 novices who performed the task 10
      times over 3 days (1 h daily). Data were collected on the time taken, error
      score, economy of movement, and total score. Test differences were analyzed
      through percentage scores and t-tests for paired samples. RESULTS: Improvement
      was greatest over tests 1 to 5 (improvement: test(1.2), 38.07%; p = 0.000;
      test(4.5), 10.66%; p = 0.010): between tests 5 and 10, improvement slowed and
      scores stabilized. Variation in participants' performance fell steadily over the
      10 tests. CONCLUSION: Trainees should perform at least 10 tests of the traversal
      task-five to get used to the equipment and task (automation phase; target total
      score, 95.16) and five to stabilize and consolidate performance (test 10 target
      total score, 74.11).

PMID- 16424993
TI  - 1H, 13C and 15N resonance assignment of the N-terminal domain of PilB from
      Neisseria meningitidis.

PMID- 16424992
TI  - Comparison of different training models for laparoscopic surgery in neonates and
      small infants.
AB  - BACKGROUND: Minimally invasive surgery in small children and infants requires
      special skills and training. This experimental study compares the efficiency of
      an in vitro pelvic trainer (PT) and an a in vivo animal model (AM). METHODS: For
      this study, 12 residents were prospectively randomized into two groups.
      Initially, all had to pass a basic skill assessment (3 tasks). Then endoscopic
      small bowel biopsy was performed (8 times) either with the in vitro PT (group A)
      or the in vivo AM (group B). Finally, all had to demonstrate this procedure in
      the in vivo AM and repeat the basic skill assessment. A quality index
      (complications, suture, biopsy) was evaluated. RESULTS: Initially, there was no
      difference between the two groups. Interestingly, the mean regression gradient of
      the index for the in vitro PT (group A) was significantly better than for the in
      vivo AM (group B). In the final in vivo operation, however, the mean index for
      the in vitro PT (group A) worsened significantly, whereas it increased for the in
      vivo AM (group B) (p = 0.037). CONCLUSION: Adequate training for an isolated
      mechanical task such as gut biopsy can be supplied using a pelvic trainer or
      animal model with similar effects. However in vivo performance of the same task
      requires secondary surgical skills, which are conveyed during live training with
      greater success. Consequently, stepwise teaching with both modules seems
      reasonable before these procedures are approached in neonates or small children.

PMID- 16424994
TI  - Comparison of buffered and unbuffered local anaesthesia for inguinal hernia
      repair: a prospective study.
AB  - Bicarbonate buffered local anaesthetic solutions are known to reduce the pain of
      infiltration. However, its efficacy in reducing the pain of infiltration in
      patients undergoing inguinal hernia repair has never been tested. This study aims
      to test the efficacy of bicarbonate buffered solution in reducing the pain of
      infiltration and pain for the total surgical procedure in a series of patients
      undergoing elective inguinal hernia repair. Forty consecutive male patients with
      unilateral, reducible inguinal hernias were studied prospectively. All patients
      underwent surgery under local anaesthesia, the first 20 with unbuffered solution
      and the next 20 using buffered solution. Pain scores were obtained for the
      infiltration in the anaesthetic room and for the total surgical procedure. In
      addition, satisfaction scores were obtained at the end of the procedure. The mean
      pain score for the initial infiltration of unbuffered anaesthetic was 3.00 (range
      0-5), and for the buffered anaesthetic it was 1.45 (range 0-4), P=0.02. The mean
      pain score for the entire procedure for the unbuffered group was 3.05 (range 0
      6), and for the buffered group it was 1.45 (range 0-5), P=0.02. The patient
      satisfaction rate was higher with the buffered solution compared to unbuffered
      solution (P<0.05). There were no complications reported with either solution.
      Buffered local anaesthetic solution significantly reduces the perceived pain of
      inguinal hernia repair, both during the infiltration and during the procedure
      itself. It is safe to administer and it results in a high rate of patient
      satisfaction.

PMID- 16424995
TI  - Surgical and radiologic anatomy.

PMID- 16424997
TI  - [Thyroid gland diseases--interdisciplinary management].

PMID- 16424996
TI  - Evaluation of the effects of cadmium on rat liver.
AB  - Cadmium is one of the most toxic pollutants in environment. Cadmium accumulation
      in blood affects the renal cortex and causes renal failure. In this study, we
      aimed to evaluate the effects of cadmium on rat liver tissue. Eighteen male
      albino rats aged ten weeks old were used in the study. 15 ppm of cadmium was
      administered to rats via consumption water daily. At the end of the 30th study
      day, the animals were killed under ether anesthesia. After the liver tissue
      samples were taken, histopathological and biochemical examinations were
      performed. Histopathologic changes have included vacuolar and granular
      degenerations in hepatocytes, heterochromatic nucleuses and sinusoidal and portal
      widenings. Central vein diameters were normal in cadmium exposed group. Whereas,
      there was statistically significant difference between two groups by means of
      sinusoidal (p< 0.001) and portal triad diameters (p< 0.01). Malondialdehyde (MDA)
      is an indicator of lipid peroxidation. In this study, MDA was used as a marker of
      oxidative stress-induced liver impairment in cadmium exposed rats. Superoxide
      dismutase (SOD) and catalase (CAT) activities were also measured to evaluate the
      changes in antioxidative system in liver tissues. Current findings showed that
      MDA levels were increased and SOD and CAT activities were decreased in cadmium
      exposed group compared to control group. The difference between two groups was
      statistically significant (pvalues: MDA,p< 0.01; CAT,p< 0.01 and SOD,p< 0.05). In
      conclusion, these findings suggest the role of oxidative mechanisms in cadmium
      induced liver tissue damage.

PMID- 16424998
TI  - [Diagnosis, treatment and follow-up in the case of differentiated thyroid
      cancer].
AB  - For early diagnosis of thyroid cancer, ultrasonography (US) and US-guided fine
      needle aspiration biopsy are the methods of choice. Thyroid scintigraphy using Tc
      99m pertechnetate can underline the necessity of surgery in case of
      hypofunctioning nodules. Treatment of thyroid cancer includes total thyroidectomy
      and staging lymphadenectomy, in the case of lymph node metastases, radical neck
      dissection of the ipsilateral side. Four weeks after surgery, if TSH exceeds a
      value of 50 mU/l, with the exception of papillary thyroid cancer pT1a (TNM 1997),
      radioiodine remnant ablation using activities between 2960 and 3700 MBq I-131 is
      performed in all other cases. As growth of benign and malignant thyroid cells
      depends on TSH stimulation, thyroid hormone therapy using TSH suppressive doses
      (TSH, <0.03 mU/l) follows radioiodine remnant ablation. Additional fractionated
      external radiation therapy (50 Gy) may be administered in advanced cases (e.g.,
      pT4 N1M0; TNM 1997). Standard follow-up of differentiated thyroid cancer includes
      measurement of serum thyroglobulin, US of the neck and I-131 whole-body
      scintigraphy (I-131 WBS). With about 98% the sensitivity of thyroglobulin is very
      high under TSH stimulation. In case of elevated thyroglobulin, US is the method
      of choice to detect local recurrences and lymph node metastases of the neck. At
      defined intervals of follow-up or in case of increasing thyroglobulin, I-131 WBS
      will be performed under TSH stimulation. With the availability of recombinant TSH
      (exogenous TSH stimulation) the need to withdraw thyroid hormone over a period of
      3-4 weeks (endogenous TSH stimulation) is no longer necessary to perform I-131
      WBS. However, in about 20-40% of cases or in the course of disease after several
      radioiodine therapies, recurrences or metastases may be or become iodine
      negative. In this case, cationic complexes such as Tc-99m Sestamibi or Tc-99m
      Tetrofosmin are available to detect less differentiated metastases. In the course
      of dedifferentiation of malignant thyroid cells, the ability of iodine uptake
      decreases and uptake of glucose increases. This elevated glucose metabolism can
      be imaged using FDG PET. Today the combination of PET (metabolic imaging) and CT
      (morphologic imaging) using PET/CT fusion imaging is the method of choice to
      image iodine-negative metastases.

PMID- 16424999
TI  - [Thyroid and cardiovascular system].
AB  - The cardiocirculatory changes in hyperthyroidism seem to be an accommodation to
      the increased metabolic demands and lead to an increased perfusion of the
      peripheral tissues. Due to the influence of elevated thyroid hormone levels,
      contractility, stroke volume, resting heart rate, and contraction and relaxation
      velocity of the left ventricle increase. Caused by direct effect on the smooth
      vascular muscle, systemic vascular resistance is decreased with the consequence
      of a diminished afterload and an increased cardiac efficiency. The activation of
      the renin-angiotensin-aldosteron system and the increased production of
      erythropoietin additionally lead to an increased blood volume, which increases
      cardiac preload together with the increased venous backflow. Manifest
      hypothyroidism is characterized by bradycardia and diastolic dysfunction in rest
      and systolic dysfunction at stress. Despite a slight increase of diastolic blood
      pressure due to an increased systemic vascular resistance, blood pressure remains
      nearly stable because of diminished cardiac output. Hypercholesterinaemia and
      diastolic hypertension in hypothyroid patients can lead to the development of
      arteriosclerosis and coronary heart disease (CHD). Also subclinical
      hypothyroidism is associated with a significantly higher risk for
      arteriosclerosis and CHD, whereas subclinical hyperthyroidism seems to be
      associated with an increased mortality for all reasons, especially for
      cardiovascular diseases.

PMID- 16425000
TI  - [Effects of thyroid disorders on the bone].
AB  - Interactions between thyroid hormones and the bone are complex and are still not
      fully understood. During development, thyroid hormone is essential for the
      recruitment and maturation of bone cells. A deficit of thyroid hormone during
      pregnancy and in the newborn leads to retardation of the skeleton. Hypothyroidism
      during later life causes a relevant decrease of bone turnover. Excessive amounts
      of thyroid hormone induce increased activity of osteoblasts and osteoclasts
      leading to high bone turnover and a loss of BMD, as the activity of osteoclasts
      predominates over the activity of osteoblasts. In subclinical hyperthyroidism,
      premenopausal women show no significant BMD loss, whereas postmenopausal women
      face a significant BMD loss. Men seem to have a limited, but significant bone
      loss in subclinical hyperthyroidism. Therapeutic consequences focus on the
      normalization of thyroid function, which can lead to restoration of BMD and
      normalization of bone turnover. In particular, patients on long-term suppressive
      L-thyroxine therapy or anti-thyroid drug medication benefit from additional
      antiresorptive treatment. This article surveys the complex interactions between
      thyroid hormones and bone cells and their effects on bone turnover, BMD and
      fractures according to the different states of thyroid function.

PMID- 16425001
TI  - [Schilddruse und polyendokrinopathien].
AB  - The thyroid gland can be affected in the course of several polyendocrinopathy
      syndromes either by impairment of physiological function or thyroid carcinoma.
      The various syndromes -- polyglandular autoimmune syndrome, autoimmune
      hypophysitis, multiple pituitary hormone deficiency, multiple endocrine
      neoplasia, and Carney complex -- are discussed. Therapy of thyroid dysfunction is
      identical whether it is part of a specific syndrome or not. Genetic testing for
      mutations, however, has had an enormous impact on screening procedures and
      therapeutic consequences.

PMID- 16425002
TI  - [Thyroid dysfunction in aged persons].
AB  - This is a short review about thyroid dysfunction in the elderly. Screening
      investigations from the United States have shown that nearly every 4th woman
      above the age of 65 is affected. Therefore a state-of-the-art article about this
      phenomenon seems justified. Epidemiologic studies show that the pattern of
      thyroid dysfunction depends on the iodine-nutrient status, thyrotoxicosis being
      more common in countries with iodine deficiency, overt and subclinical
      hypothyroidism occurring very frequently in areas with sufficient iodine
      supplementation. After discussing the state of the art of what is known about
      physiologic changes induced by age in the hypothalamic-pituitary-thyroid axis, it
      is pointed out that abnormal values of thyroid function parameters in serum
      should be further investigated. Symptoms of thyroid dysfunction are very rare and
      often unspecific. Therefore, laboratory screening in women above the age of 65
      seems to be justified. Finally, the differences of treating elderly patients with
      thyroid dysfunction in comparison to treating young patients is discussed. In
      this discussion the impact of subclinical disturbances of thyroid dysfunction is
      included.

PMID- 16425003
TI  - [Rokitansky and Virchow: throes about the scientific term of disease].
AB  - The scientific conception of disease became established in the 19th century and
      resulted in medicine becoming a branch of the natural sciences. In Vienna, the
      development of pathoanatomy is closely linked with the work of Carl Rokitansky,
      who used the postmortem examination to draw conclusions that would guide the
      physician in making future clinical diagnoses. It were Rokitansky and Skoda who
      developed the II. Viennese School, the "young Viennese School". The founder of
      the new school of medicine was thus a pathoanatomist. In 1846, Rokitansky
      published the first volume of his "Compendium of General Pathological Anatomy".
      In Berlin, there was at the time a particularly avid group of young physicians
      who had learned to "think cellularly". Rudolf Virchow, a member of the group, was
      asked to review the newly published volume of Rokitansky's compendium. The 25
      year-old was particularly scathing in his criticism, determined to prevent a new
      dyscrasia theory right from the very beginning. For the next edition of his work,
      Rokitansky rewrote the "compendium" completely, now in natural scientific terms,
      and in doing so, encouraged Virchow to further develop the natural scientific
      conception of disease. Rokitansky's factual approval thus gave Virchow valuable
      support on his way to cellular pathology.

PMID- 16425005
TI  - [Psychotherapeutic medicine].

PMID- 16425007
TI  - [Somatoform and factitious disorders in clinical medicine].
AB  - Patients with "medically unexplained somatic symptoms" are frequent in every
      health care system. The bodily complaints may persist over a long period of time,
      cause serious subjective suffering and be associated with secondary psychiatric
      comorbidity and major disabilities in psychosocial life. The doctor-patient
      relationship is often hampered by emotional conflicts, leading to unsuccessful
      treatment, doctor-shopping and chronic courses of illness. A major subgroup of
      patients with somatoform disorders and a minor subgroup of patients with self
      induced, i.e., factitious disorders must be differentiated, both showing a
      complex etiopathogenesis of their somatic symptoms. Patients with somatoform and
      factitious disorders present a special challenge within the health care system.

PMID- 16425006
TI  - [Anthropological aspects of psychiatry].
AB  - Methods, diagnostic and therapeutic patterns in psychiatry have had, since its
      advent in the late 19th century, to evolve fast in order to reach the level of
      the other medical disciplines. Simultaneously, the "shrinking" of the world as a
      result of technological developments and increase in world population with the
      ensuing mass migration has meant that contacts between very heterogeneous
      cultures have intensified. This in turn has made it paramount for psychiatry to
      move away at least to some extent from its traditional Euro-American orientation
      and adopt a broader, global and transcultural approach to psychiatric problems.
      It will have to take into account the cultural backgrounds of the human beings it
      proposes to examine and treat.

PMID- 16425008
TI  - [Successful coping and experience-dependent brain plasticity].
AB  - Recent progress in brain research has shown that the human brain, i.e., the
      neuronal and synaptic connectivity especially in higher cortical association
      centres, is much more plastic and use-dependent than previously thought. This
      contribution summarizes the present knowledge about this phenomenon of experience
      dependent plasticity. Irritation, anxiety and the activation of the
      neuroendocrine stress-response-system is the most important trigger for the
      adaptive modification and reorganization of neuronal networks and synaptic
      connectivity. The experience and successful mastery of a large spectrum of
      different challenges already during early childhood and during later life
      diminish the risk of the acquisition and facilitation of maladaptive coping
      strategies. Once established, the strongly facilitated neuronal networks involved
      in the generation of maladaptive behavioural patterns are difficult to
      reorganize. The experience of loss of control and the long-lasting activation of
      an uncontrollable stress response may contribute to the destabilization of the
      neuronal connectivity established in the course of acquisition of such
      maladaptive coping strategies.

PMID- 16425009
TI  - [Perspectives on psycho-oncology and tumor-related fatigue].
AB  - Psycho-oncology -- as the diction suggests -- is a multidisciplinary sub
      specialty of oncology concerned with the emotional responses of patients at all
      stages of the disease, their families and staff. Psycho-oncology does not assume
      the responsibility of cancer cure but attends to the psychological, social and
      behavioural variables that influence cancer prevention, risk and survival. The
      psycho-social research domains today contain the screening and management of
      psycho-social distress as well as experiences with specific psycho-oncological
      symptoms. Cancer-related fatigue, for example, disturbs patients' quality of life
      more often than pain. However, all too often doctors fail to pay enough attention
      to this unknown symptom.

PMID- 16425010
TI  - [Addiction--who is not affected?].
AB  - Addiction and addiction-related behaviour increased during the past decades.
      Several substances with psychoactive attributes, like opioids, cocaine or
      alcohol, can lead to dependence with physical and/or mental symptoms. In addition
      to substance-related addiction, non-substance-related dependence requires special
      attention. Increasing numbers of workaholics and patients suffering from internet
      addiction, gambling or eating-disorders can be observed. To meet international
      treatment standards for addiction, diversification of therapy is necessary and,
      additionally, gender-related aspects in development and treatment of dependence
      and addiction-related behaviour are essential for state-of-the-art therapy of
      this patient population.

PMID- 16425011
TI  - [Borders of life and medicine].

PMID- 16425012
TI  - [On the necessity of open discourses in medicine].

PMID- 16425016
TI  - Cytochrome f from the Antarctic psychrophile, Chlamydomonas raudensis UWO 241:
      structure, sequence, and complementation in the mesophile, Chlamydomonas
      reinhardtii.
AB  - Although cytochrome f from the Antarctic psychrophile, Chlamydomonas raudensis
      UWO 241, exhibits a lower apparent molecular mass (34 kD) than that of the
      mesophile C. reinhardtii (41 kD) based on SDS-PAGE, both proteins are comparable
      in calculated molecular mass and show 79% identity in amino acid sequence. The
      difference in apparent molecular mass was maintained after expression of petA
      from both Chlamydomonas species in either E. coli or a C. reinhardtii DeltapetA
      mutant and after substitution of a unique third cysteine-292 to phenylalanine in
      the psychrophilic cytochrome f. Moreover, the heme of the psychrophilic form of
      cytochrome f was less stable upon heating than that of the mesophile. In contrast
      to C. raudensis, a C. reinhardtii DeltapetA mutant transformed with petA from C.
      raudensis exhibited the ability to undergo state transitions and a capacity for
      intersystem electron transport comparable to that of C. reinhardtii wild type.
      However, the C. reinhardtii petA transformants accumulated lower levels of
      cytochrome b ( 6 ) /f complexes and exhibited lower light saturated rates of O(2)
      evolution than C. reinhardtii wild type. We show that the presence of an altered
      form of cytochrome f in C. raudensis does not account for its inability to
      undergo state transitions or its impaired capacity for intersystem electron
      transport as previously suggested. A combined survey of the apparent molecular
      mass, thermal stability and amino acid sequences of cytochrome f from a broad
      range of mesophilic species shows unequivocally that the observed differences in
      cytochrome f structure are not related to psychrophilly. Thus, caution must be
      exercised in relating differences in amino acid sequence and thermal stability to
      adaptation to cold environments.

PMID- 16425017
TI  - Inhibitory effects of various L-type and T-type calcium antagonists on
      electrically generated, potassium-induced and carbachol-induced contractions of
      porcine detrusor muscle.
AB  - The inhibitory effects of different calcium antagonists on contractions of
      isolated porcine detrusor muscle were investigated. Suppression of the maximum
      potassium-induced contraction and electrically generated contractions by
      nifedipine, verapamil and diltiazem were investigated. Furthermore, concentration
      response curves of carbachol after pretreatment with the L-type antagonists
      nifedipine, verapamil, diltiazem, nimodipine and the T-type antagonist mibefradil
      at different concentrations were performed. Nifedipine significantly reduced the
      potassium-induced maximum contraction to 89, 60, 21, 8 and 4% (10(-9)-10(-5) M).
      Verapamil and diltiazem significantly reduced it to 64, 30 and 5% (10(-7)-10(-5)
      M) or 79, 27, 7 and 1% (10(-7)-10(-4) M), respectively. Nifedipine, verapamil and
      diltiazem significantly reduced the electrically generated contraction to 55, 36,
      34 and 25% (10(-7)-10(-4) M), 71, 32 and 2% (10(-6)-10(-4) M), 96, 78, 38 and 5%
      (10(-7)-10(-4) M), respectively. pD2 values of nifedipine, verapamil and
      diltiazem amounted to 7.07, 5.56 and 5.40 and differed significantly. After
      pretreatment with nifedipine at 10(-6) M, the concentration-response curve of
      carbachol was nearly suppressed. The effects of nimodipine, verapamil and
      diltiazem were smaller. Mibefradil caused only at 10(-5) M a significant
      reduction. All investigated L-type calcium antagonists were strong inhibitors of
      the examined contractions. Nifedipine showed the biggest inhibitory effect.

PMID- 16425018
TI  - Metabolic costs of avian flight in relation to flight velocity: a study in Rose
      Coloured Starlings (Sturnus roseus, Linnaeus).
AB  - The metabolic costs of flight at a natural range of speeds were investigated in
      Rose Coloured Starlings (Sturnus roseus, Linnaeus) using doubly labelled water.
      Eight birds flew repeatedly and unrestrained for bouts of 6 h at speeds from 9 to
      14 m s(-1) in a low-turbulence wind tunnel, corresponding to travel distances
      between 200 and 300 km, respectively. This represents the widest speed range
      where we could obtain voluntarily sustained flights. From a subset of these
      flights, data on the wing beat frequency (WBF) and intermittent flight behaviour
      were obtained. Over the range of speeds that were tested, flight costs did not
      change with velocity and were on an average 8.17+/-0.64 W or 114 W kg(-1). Body
      mass was the only parameter with a significant (positive) effect on flight costs,
      which can be described as EE(f)=0.741 M(0.554). WBF changed slightly with speed,
      but correlated better with body mass. Birds showed both types of intermittent
      flight, undulating and bounding, but their frequencies did not systematically
      change with flight speed.

PMID- 16425019
TI  - Lithogenesis: induction of renal calcifications by nanobacteria.
AB  - Nanobacteria have been isolated from kidney stones and it has been suggested that
      they may act as a nucleus for the initiation of the renal stones. In the present
      study, we examine their role in biocrystallization and their in vivo effects on
      kidney pathology. Calcium oxalate monohydrate (COM) assay was carried out in the
      presence of nanobacteria to study biocrystallization. Wistar rats were given an
      intravenous injection of nanobacteria and the kidneys were examined for
      pathological changes. The COM assay showed accelerated biocrystallization of
      (14)C-oxalate in the presence of nanobacteria, indicating them to be efficient
      candidates for biomineralization. Histopathological studies revealed bacteria
      induced renal tubular calcifications and various manifestations of infection. Our
      studies confirm that nanobacteria may be involved in the pathogenesis of renal
      tubular calcification.

PMID- 16425020
TI  - Prevalence of urolithiasis in the autonomous city of Buenos Aires, Argentina.
AB  - Urolithiasis is the third most common pathological disease afflicting the urinary
      tract, and usually occurs between the third and fourth decades of an individual's
      life. Epidemiological studies about this condition are lacking in our country. In
      1998, we performed an epidemiological, cross-sectional study of the prevalence of
      urolithiasis in a sample of 1,086 subjects, which included men and women of all
      ages, selected from the general population of the city of Buenos Aires. The
      method used to gather basic information was an auto administered questionnaire
      about the present or past history of urolithiasis that was handled at the
      dwelling by a trained volunteer. We found a 3.96% lifetime prevalence of
      urolithiasis in the general population of Buenos Aires. The rate was slightly
      higher in men (4.35%) than in women (3.62%), with a male to female ratio of
      1.19:1. No case of urolithiasis was found in subjects under the age of 20. In
      subjects over 19 years, the prevalence rate of the disease was 5.14%; 5.98% for
      men (CI 3.41-8.55%) and 4.49% for women (CI 2.61-6.37%). Prevalence increased
      with age, ranging from 2.75% in the 20-39 age group to 7.79% in those >or=60
      years. The life time prevalence rate of urolithiasis observed in Buenos Aires is
      similar to that reported in a few other studies performed among males and females
      in the general population of USA and Europe. Prevalence of urolithiasis increases
      with age both in men and in women.

PMID- 16425021
TI  - Effect of potential renal acid load of foods on urinary citrate excretion in
      calcium renal stone formers.
AB  - The aim of this study was to investigate the influence of the potential renal
      acid load (PRAL) of the diet on the urinary risk factors for renal stone
      formation. The present series comprises 187 consecutive renal calcium stone
      patients (114 males, 73 females) who were studied in our stone clinic. Each
      patient was subjected to an investigation including a 24-h dietary record and 24
      h urine sample taken over the same period. Nutrients and calories were calculated
      by means of food composition tables using a computerized procedure. Daily PRAL
      was calculated considering the mineral and protein composition of foods, the mean
      intestinal absorption rate for each nutrient and the metabolism of sulfur
      containing amino acids. Sodium, potassium, calcium, magnesium, phosphate,
      oxalate, urate, citrate, and creatinine levels were measured in the urine. The
      mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/
      20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18)
      was found between daily PRAL and daily urinary citrate, but no correlation
      between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary
      calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly
      related to the dietary intake of protein. Daily urinary citrate was significantly
      related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20,
      P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The
      regression analysis by stepwise selection confirmed the significant negative
      correlation between PRAL and urinary citrate (P=0.002) and the significant
      positive correlation between riboflavin and urinary citrate (P=0.000). Urinary
      citrate excretion of renal stone formers (RSFs) is highly dependent from dietary
      acid load. The computation of the renal acid load is advisable to investigate the
      role of diet in the pathogenesis of calcium stone disease and it is also a useful
      tool to evaluate the lithogenic potential of the diet of the individual patient.

PMID- 16425022
TI  - The effect of semi-dwarf genes on root system size in field-grown barley.
AB  - Root system size (RSS) was measured in 12 diverse barley genotypes and 157 double
      haploid lines (DHs), using electric capacitance. The parents of the DHs, Derkado
      and B83-12/21/5, carry different semi-dwarfing genes, sdw1 and ari-e.GP,
      respectively. Estimates of RSS were taken in the field thrice during plant
      development: stem elongation (RSS1), heading (RSS2) and grain filling (RSS3). The
      12 barley genotypes were assessed over 3 years and at two or three locations each
      year; the DH mapping population was assessed at two locations in 2002. Among the
      12 barley genotypes, those with the semi-dwarf genes had greater RSS values in
      all 3 years (28.9, 24.6 and 15.0% in years 1, 2 and 3, respectively) compared to
      non-semi-dwarf controls. The DH population showed transgressive segregation on
      both sides of the parent means, indicating polygenic control of RSS. Quantitative
      trait loci (QTLs) for RSS were found on five of the seven chromosomes: 1H, 3H,
      4H, 5H and 7H and these were compared with previously mapped agronomic traits.
      The TotalRSS QTL on 3H was associated with sdw1 and QTLs for height, plant yield
      and plant weight. The RSS3 QTL on 5H was associated with ari-e.GP and QTLs for
      height, plant yield, plant weight, harvest index and tiller number. The RSS3 QTL
      on 7H was also associated with a TotalRSS QTL and QTLs for plant weight and
      harvest index. Other RSS QTLs were not associated with any other trait studied.
      RSS is considered to be a polygenic trait linked to important traits, in
      particular to yield. The study highlights the effects of semi-dwarfing genes and
      discusses the potential for breeding for root traits.

PMID- 16425023
TI  - Myosin flares and actin leptomeres as myofibril assembly/disassembly
      intermediates in sonic muscle fibers.
AB  - The sonic muscle of type 1 male midshipman fish produces loud and enduring mating
      calls. Each sonic muscle fiber contains a tubular contractile apparatus with
      radially arranged myofibrillar plates encased in a desmin-rich cytoskeleton that
      is anchored to broad Z bands (approximately 1.2 micro m wide). Immunomicroscopy
      has revealed patches of myosin-rich "flares" emanating from the contractile tubes
      into the peripheral sarcoplasm along the length of the fibers. These flares
      contain swirls of thick filaments devoid of associated thin filaments. In other
      regions of the sarcoplasm at the inner surface of the sarcolemma and near Z
      bands, abundant ladder-like leptomeres occur with rungs every 160 nm. Leptomeres
      consist of dense arrays of filaments (approximately 4 nm) with a structure that
      resembles myofibrillar Z band structure. We propose that flares and leptomeres
      are distinct filamentous arrays representing site-specific processing of
      myofibrillar components during the assembly and disassembly of the sarcomere.
      Recent reports that myosin assembles into filamentous aggregates before
      incorporating into the A band in the skeletal muscles of vertebrates and
      Caenorhabditis elegans suggest that sonic fibers utilize a similar pathway. Thus,
      sonic muscle fibers, with their tubular design and abundant sarcoplasmic space,
      may provide an attractive muscle model to identify myofibrillar intermediates by
      structural and molecular techniques.

PMID- 16425024
TI  - Kappa light chain myeloma with initial cutaneous involvement.

PMID- 16425025
TI  - Del(5q) and MLL amplification in homogeneously staining region in acute
      myeloblastic leukemia: a recurrent cytogenetic association.
AB  - We report here a 71 year-old female presenting with acute myeloblastic leukemia
      (FAB-M1) after treatment of essential thrombocythemia with Vercyte. Conventional
      cytogenetic techniques showed a complex karyotype, 44,XX,-5,-7,-11,add(11)(q23),
      14,+mar,+r. The use of several fluorescent in situ hybridizations (FISH) lead to
      the identification of these complex rearrangements. The marker was found to be
      tricentric, with pericentromeric material of chromosome 7 inserted in the short
      arm of chromosome 5, resulting in monosomy 5q and 7q. The derivative chromosome
      11 was dicentric and had subtelomeric sequences of 11p on both ends; several
      copies of the MLL gene were located in two different regions separated by a
      centromere of chromosome 11. Twenty-one cases, including ours, of myelodysplastic
      syndromes and acute myelogenous leukemia with MLL amplification present in hsr or
      dmin were found in the literature. Most of these patients shared some
      characteristics: they were old, they had de novo acute myeloid leukemia (AML)
      with a complex karyotype and a short survival, 90% of them having also a del(5q).
      Therefore, the simultaneous presence of MLL amplification and del(5q) appears to
      be a nonrandom association that could be the signature of AML in elderly patients
      with a poor prognosis.

PMID- 16425026
TI  - Detection of lesions in multiple sclerosis by 2D FLAIR and single-slab 3D FLAIR
      sequences at 3.0 T: initial results.
AB  - The aim of this study was to compare conventional 2D FLAIR and single-slab 3D
      FLAIR sequences in the detection of lesions in patients with multiple sclerosis.
      Eight patients with MS were examined at 3.0 T by using a 2D FLAIR sequence and a
      single-slab 3D FLAIR sequence. A comparison of lesion detectability was performed
      for the following regions: periventricular, nonperiventricular/juxtacortical and
      infratentorial. The contrast-to-noise ratios (CNRs) between lesions and brain
      tissue and CSF were calculated for each sequence. A total of 424 lesions were
      found using the 2D FLAIR sequence, while with the 3D FLAIR sequence 719 lesions
      were found. With the 2D FLAIR sequence, 41% fewer lesions were detected than with
      the 3D FLAIR sequence. Further, 40% fewer supratentorial and 62.5% fewer
      infratentorial lesions were found with the 2D FLAIR sequence. In images acquired
      with the 3D FLAIR sequence, the lesions had significantly higher CNRs than in
      images acquired with the 2D FLAIR sequence. These are the first results using a
      single-slab 3D FLAIR sequence at 3.0 T for detection of lesions in patients with
      MS. With the 3D FLAIR sequence significantly higher CNRs were achieved and
      significantly more lesions in patients with MS were detected.

PMID- 16425027
TI  - Cervical cancer: MR imaging findings before, during, and after radiation therapy.
AB  - In this study, magnetic resonance (MR) imaging findings of patients with varying
      stages of cervical carcinoma are reviewed. The appearances of the postirradiation
      pelvis on MR images are also characterized and correlated with preradiation
      therapy staging. MR imaging findings of recurrent and metastatic disease are
      presented and discussed.

PMID- 16425030
TI  - High levels of asparagine synthetase in hypocotyls of pine seedlings suggest a
      role of the enzyme in re-allocation of seed-stored nitrogen.
AB  - A pine asparagine synthetase gene expressed in developing seedlings has been
      identified by cloning its cDNA (PsAS1) from Scots pine (Pinus sylvestris L.).
      Genomic DNA analysis with PsAS1 probes and a sequence-based phylogenetic tree are
      consistent with the possibility of more than one gene encoding asparagine
      synthetase in pine. However, the parallel patterns of free asparagine content and
      PsAS1 products indicate that the protein encoded by this gene is mainly
      responsible for the accumulation of this amino acid during germination and early
      seedling development. The temporal and spatial patterns of PsAS1 expression
      together with the spatial distribution of asparagine content suggest that, early
      after germination, part of the nitrogen mobilized from the megagametophyte is
      diverted toward the hypocotyl to produce high levels of asparagine as a reservoir
      of nitrogen to meet later specific demands of development. Furthermore, the
      transcript and protein analyses in seedlings germinated and growth for extended
      periods under continuous light or dark suggest that the spatial expression
      pattern of PsAS1 is largely determined by a developmental program. Therefore, our
      results suggest that the spatial and temporal control of PsAS1 expression
      determines the re-allocation of an important amount of seed-stored nitrogen
      during pine germination.

PMID- 16425031
TI  - Evolutionary comparison of the reproductive genes, DAZL and BOULE, in primates
      with and without DAZ.
AB  - Genes of the DAZ (Deleted in AZoospermia) gene family, DAZ, DAZL (DAZ-Like), and
      BOULE, encode closely related RNA-binding proteins that are required for
      fertility in numerous organisms, yet the genomes of different organisms possess
      different complements of DAZ family genes. Thus, invertebrates such as flies and
      worms contain just a single DAZ homolog, boule, while genomes of vertebrates,
      other than catarrhine primates (Old World monkeys and hominids), possess both
      Boule and Dazl genes. Finally, catarrhine primates possess BOULE, DAZL, and DAZ
      genes. Since the DAZ genes arose recently in evolution in the catarrhine lineage,
      we sought to examine how the sequences and expression of this gene family may
      have changed after the introduction of a new member, DAZ. Based on previous
      results, we hypothesized that the introduction of a new member of the DAZ gene
      family into catarrhines could reduce functional constraint on DAZL. Surprisingly,
      however, we found that platyrrhine DAZL demonstrated significantly more sequence
      divergence than catarrhine DAZL (p=0.0006 for nucleotide and p=0.05 for amino
      acid sequence); however, comparison of K (a)/K (s) ratios suggests that the DAZL
      and BOULE genes are under similar functional constraints regardless of lineage.
      Thus, our data are most consistent with the hypothesis that the introduction of
      DAZ did not affect the evolution of DAZL or BOULE, and that a higher neutral
      mutation rate in platyrrhines than in catarrhines, along with the greater
      tolerance of DAZL for variation relative to BOULE, may be the foundation for the
      observed differences in sequence divergence in this gene family.

PMID- 16425032
TI  - No-carrier-added versus carrier-added123I-metaiodobenzylguanidine for the
      assessment of cardiac sympathetic nerve activity.
AB  - PURPOSE: No-carrier-added (nca) MIBG is primarily associated with specific uptake
      (i.e. uptake-1 mechanism). We evaluated the hypothesis that nca MIBG will be less
      influenced by changes in extra-neuronal uptake (i.e. uptake-2 mechanism) compared
      with carrier-added (ca) MIBG. METHODS: No-carrier-added MIBG was compared with ca
      MIBG of two different manufacturers (ca MIBG-1 and ca MIBG-2, with a specific
      activity of 200 Mq/mumol and 40 MBq/mumol MIBG respectively) in rats (n=6 per
      group): controls, blocking uptake-1 (desipramine) and blocking uptake-2
      (phenoxybenzamine hydrochloride). Dedicated pinhole SPECT was performed 2 h after
      injection of the radiotracer. After SPECT, biodistribution was assessed [%
      injected dose per gram tissue (%ID)]. RESULTS: No-carrier-added MIBG had the
      highest absolute cardiac uptake. Although a clear trend was observed, nca MIBG
      was not statistically significantly different from ca MIBG-1 (0.31+/-0.05 %ID vs
      0.25+/-0.01 %ID,p=0.05). Blocking uptake-1 resulted in a significant decrease in
      absolute cardiac uptake only for nca MIBG (0.22+/-0.03 %ID,p=0.004). Blocking
      uptake-2 resulted in a significant reduction in ca MIBG-1 cardiac uptake (0.14+/
      0.02 %ID,p=0.0001), but not in the cardiac uptake of nca MIBG or MIBG-2. SPECT
      showed the highest relative cardiac uptake for nca MIBG. Poor contrast between
      myocardium and surrounding tissue hampered assessment of relative cardiac uptake
      on SPECT of both ca MIBG-1 and ca MIBG-2. CONCLUSION: No-carrier-added MIBG
      yields a higher myocardial uptake than ca MIBG and is associated with a higher
      specific as well as a lower non-neuronal uptake. We therefore conclude that for
      the scintigraphic assessment of the myocardial sympathetic nervous system, nca
      MIBG is to be preferred over ca MIBG.

PMID- 16425033
TI  - Intracellular sodium increase and susceptibility to ischaemia in hearts from type
      2 diabetic db/db mice.
AB  - AIMS/HYPOTHESIS: An important determinant of sensitivity to ischaemia is altered
      ion homeostasis, especially disturbances in intracellular Na(+) (Na(i)(+))
      handling. As no study has so far investigated this in type 2 diabetes, we
      examined susceptibility to ischaemia-reperfusion in isolated hearts from diabetic
      db/db and control db/+ mice and determined whether and to what extent the amount
      of (Na(i)(+)) increase during a transient period of ischaemia could contribute to
      functional alterations upon reperfusion. METHODS: Isovolumic hearts were exposed
      to 30-min global ischaemia and then reperfused. (23)Na nuclear magnetic resonance
      (NMR) spectroscopy was used to monitor[Formula: see text] and (31)P NMR
      spectroscopy to monitor intracellular pH (pH(i)). RESULTS: A higher duration of
      ventricular tachycardia and the degeneration of ventricular tachycardia into
      ventricular fibrillation were observed upon reperfusion in db/db hearts. The
      recovery of left ventricular developed pressure was reduced. The increase
      in[Formula: see text] induced by ischaemia was higher in db/db hearts than in
      control hearts, and the rate of pH(i) recovery was increased during reperfusion.
      The inhibition of Na(+)/H(+) exchange by cariporide significantly reduced
      (Na(i)(+)) gain at the end of ischaemia. This was associated with a lower
      incidence of ventricular tachycardia in both heart groups, and with an inhibition
      of the degeneration of ventricular tachycardia into ventricular fibrillation in
      db/db hearts. CONCLUSIONS/INTERPRETATION: These findings strongly support the
      hypothesis that increased (Na(i)(+)) plays a causative role in the enhanced
      sensitivity to ischaemia observed in db/db diabetic hearts.

PMID- 16425034
TI  - The steel ball-bearing test: a new test for evaluating protective sensation in
      the diabetic foot.
AB  - AIMS/HYPOTHESIS: The aim of the study was to assess a new steel ball-bearing test
      as a means of evaluating protective sensation in the diabetic foot. METHODS:
      Subjects were enrolled for this study as follows: (1) 39 patients (mean age
      61.3+/-9.7 years) with neuropathy and prior neuropathic ulcer (Group A); (2) 36
      patients (mean age 63.7+/-10.1 years) with neuropathy without neuropathic ulcer
      (Group B); (3) 34 patients (mean age 52.1+/-10.4 years) without neuropathy (Group
      C); and (4) 21 healthy volunteers (mean age 46.7+/-8.7 years) (Group D).
      Neuropathy was diagnosed by means of neuropathy disability score (NDS). The
      plantar area over the second metatarsal head of each foot was examined with steel
      ball-bearings of varying diameters. The smallest diameter that the patient could
      feel was used to define the ball-bearing score (range 1-6). RESULTS: A high ball
      bearing score was significantly more frequent in patients with neuropathic
      ulceration than in neuropathic patients without ulceration and in diabetic
      patients without neuropathy (p<0.001). A high score was also more frequent in
      neuropathic patients without ulceration, than in patients without neuropathy
      (p<0.001). The ball-bearing score was significantly (p=0.01) correlated with the
      NDS, the monofilament test, the vibration perception threshold and the thermal
      perception threshold. The ball-bearing test had a sensitivity of 84% and a
      specificity of 100% for impaired protective sensation due to neuropathy, and a
      sensitivity of 84.6% and a specificity of 86.1% for detection of patients with
      prior neuropathic ulceration. CONCLUSIONS/INTERPRETATION: The steel ball-bearing
      test has a high sensitivity and specificity both for the evaluation of protective
      sensation and for detection of patients with prior neuropathic ulceration.

PMID- 16425035
TI  - Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed
      to the Idd9.3 region.
AB  - Anti-Smith (anti-Sm) autoantibodies are directed to proteins in the small-nuclear
      ribonucleoprotein (snRNP) family and are considered specific for systemic lupus
      erythematosus (SLE) in both humans and mice. We previously established that
      NOD.c3c4 mice, carrying B6 and B10 congenic segments from chromosomes 3 to 4 on
      an nonobese diabetic (NOD) background, and NOD.Idd9R28 mice, carrying a B10
      segment on c4 alone, developed significant penetrance of anti-Sm antibody
      production. Here we determine autoantibody incidence in additional NOD.Idd9
      congenic strains and use a congenic mapping approach to narrow the interval
      necessary for enhanced autoantibody production to a approximately 5.6-Mb region
      containing insulin-dependent diabetes (Idd)9.3. The Idd9.3 interval contains the
      candidate molecule cluster of differentiation (CD)137, which is a member of the
      tumor necrosis factor (TNF) receptor superfamily, functions as an inducible
      costimulator of T cells, and controls T-B interactions. The NOD and B10 CD137
      alleles have sequence polymorphisms and different functional effects on T cells;
      the NOD CD137 allele mediates weaker T cell proliferative responses and decreased
      interleukin (IL)-2 production after CD137-mediated costimulation. Our work
      establishes CD137 as a candidate gene for control of autoantibody production in
      NOD.Idd9.3 congenic mice.

PMID- 16425037
TI  - Inactivation status of PCDH11X: sexual dimorphisms in gene expression levels in
      brain.
AB  - Genes escaping X-inactivation are predicted to contribute to differences in gene
      dosage between the sexes and are the prime candidates for being involved in the
      phenotype observed in individuals with X chromosome aneuploidies. Of particular
      interest is ProtocadherinX (PCDH11X or PCDHX), a recently described gene
      expressed in brain. In humans, PCDH11X has a homologue on the Y chromosome and is
      predicted to escape from X-inactivation. Employing bisulphite sequencing analysis
      we found absence of CpG island methylation on both the active and the inactive X
      chromosomes, providing a strong indication that PCDH11X escapes inactivation in
      humans. Furthermore, a sexual dimorphism in levels of expression in brain tissue
      was observed by quantitative real-time PCR, with females presenting an up to 2
      fold excess in the abundance of PCDH11X transcripts. We relate these findings to
      sexually dimorphic traits in the human brain. Interestingly, PCDH11X/Y gene pair
      is unique to Homo sapiens, since the X-linked gene was transposed to the Y
      chromosome after the human-chimpanzee lineages split. Although no differences in
      promoter methylation were found between humans and chimpanzees, evidence of an
      upregulation of PCDH11X in humans deserves further investigation.

PMID- 16425036
TI  - Identification and characterization of two related murine genes, Eat2a and Eat2b,
      encoding single SH2-domain adapters.
AB  - Human EAT-2 (SH2D1B) and SLAM-associated protein (SAP) (SH2D1A) are single SH2
      domain adapters, which bind to specific tyrosine residues in the cytoplasmic tail
      of six signaling lymphocytic activation molecule (SLAM) (SLAMF1)-related
      receptors. Here we report that, unlike in humans, the mouse and rat Eat2 genes
      are duplicated with an identical genomic organization. The coding regions of the
      mouse Eat2a and Eat2b genes share 91% identity at the nucleotide level and 84% at
      the protein level; similarly, segments of introns are highly conserved. Whereas
      expression of mouse Eat2a mRNA was detected in multiple tissues, Eat2b was only
      detectable in mouse natural killer cells, CD8+ T cells, and ovaries, suggesting a
      very restricted tissue expression of the latter. Both the EAT-2A and EAT-2B
      coimmunoprecipitated with mouse SLAM in transfected cells and augmented tyrosine
      phosphorylation of the cytoplasmic tail of SLAM. Both EAT-2A and EAT-2B bind to
      the Src-like kinases Fyn, Hck, Lyn, Lck, and Fgr, as determined by a yeast two
      hybrid assay. However, unlike SAP, the EAT-2 proteins bind to their kinase
      domains and not to the SH3 domain of these kinases. Taken together, the data
      suggest that both EAT-2A and EAT-2B are adapters that recruit Src kinases to SLAM
      family receptors using a mechanism that is distinct from that of SAP.

PMID- 16425038
TI  - Sequence diversity, natural selection and linkage disequilibrium in the human T
      cell receptor alpha/delta locus.
AB  - T cell receptors (TR), through their interaction with the major
      histocompatibility complex, play a central role in immune responsiveness and
      potentially immune-related disorders. We resequenced all 57 variable (V) genes in
      the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of
      Northern European, Mexican, African-American and Chinese descent. Two hundred and
      eighty-four single nucleotide polymorphisms (SNPs) were identified. The
      distribution of SNPs between V genes was heterogeneous, with an average of five
      SNPs per gene and a range of zero to 15. We describe the patterns of linkage
      disequilibrium for these newly discovered SNPs and compare these patterns with
      other emerging large-scale datasets (e.g. Perlegen and HapMap projects) to place
      our findings into a framework for future analysis of genotype-phenotype
      associations across this locus. Furthermore, we explore signatures of natural
      selection across V genes. We find evidence of strong directional selection at
      this locus as evidenced by unusually high values of Fst.

PMID- 16425040
TI  - Off-patent drugs in Italy. A short-sighted view?
AB  - The new Italian policy to off-patent products, although similar to recent reforms
      in other European countries, seems to use some interesting instruments and has
      achieved significant results in the past 2 years. In particular, the prices of
      branded products have been reduced for all active ingredients where a generic
      version is available. However, this strategy may raise some problems in the
      longer term. Our analysis identified two open issues that might limit the long
      term sustainability of the present scheme: the limited diffusion of generics and
      the reallocation of demand. The first stems from the new regulatory schemes which
      equate generics to branded off-patent products and exploit their presence only to
      cut prices. The second is favored by tough price competition that induces large
      companies to divert demand towards more profitable "me-too drugs." Solutions
      exist, but they are not easy to apply because so many difficulties arise when
      certain aspects of a long-standing equilibrium are modified.

PMID- 16425039
TI  - [The specialty of anesthesia outside Western medicine with special consideration
      of personal experience in the Democratic Republic of the Congo and Mongolia].
AB  - During the last decades anesthesia has developed into a wide ranging specialty in
      western countries, whereas in most developing and newly industrializing nations
      it still focuses on its core discipline, the perioperative care of the surgical
      patient. Poor socioeconomic status and inadequate financing of health systems
      result in a high burden of disease, a high rate of self-financing of healthcare
      costs by the patients, as well as insufficient personnel, infra-structural and
      material equipment of most healthcare facilities. Important limiting factors for
      anesthesia are low educational standards and a widespread lack of oxygen and
      medical gas supplies, as well as locally serviceable medical equipment. Studies
      evaluating the status of anesthesia in developing and newly industrializing
      nations in detail are urgently needed in order to provide aid on national and
      international as well as institutional and private levels for the development of
      anesthesia in poor countries.

PMID- 16425042
TI  - Thermal quality influences effectiveness of thermoregulation, habitat use, and
      behaviour in milk snakes.
AB  - We investigated the link between thermal quality and the effectiveness of
      thermoregulation in milk snakes in a thermally challenging environment. We
      defined thermoregulatory effectiveness as the extent to which an individual
      maintains its body temperature (Tb) closer to the preferred range (Tset) than
      allowed by the thermal quality of its environment. We defined thermal quality as
      the magnitude of the difference between operative environmental temperatures (Te)
      and Tset. Because ectotherms regulate body temperatures through choice of habitat
      and behavioural adjustments, we also examined the link between thermoregulation,
      habitat use and behaviour. During 2003-2004, we located 25 individuals 890 times,
      and recorded their Tb. Thermal quality was lower in the spring and fall than in
      the summer, and was lower in forests than in open habitats. Milk snakes
      thermoregulated more effectively in the spring than in the summer and fall, and
      more effectively in the forest than in open habitats. Milk snakes had a strong
      preference for open habitats in all seasons, which was likely to facilitate
      behavioural thermoregulation. The preference for open habitats was equally strong
      in all seasons and, therefore, the higher effectiveness of thermoregulation was
      not a result of altered habitat use. Instead, milk snakes modified their
      behaviour and were seen basking more and moved less in the spring than in the
      summer.

PMID- 16425041
TI  - Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG
      genes in patients with non-syndromic mental retardation.
AB  - Mental retardation (MR) is displayed by 57% of NF1 patients with microdeletion
      syndrome as a result of 17q11.2 region haploinsufficiency. We considered the
      cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) and oligodendrocyte
      myelin glycoprotein (OMG) genes, mapping in the NF1 microdeleted region, as
      candidate genes for MR susceptibility. CDK5R1 encodes for a neurone-specific
      activator of cyclin-dependent kinase 5 (CDK5) involved in neuronal migration
      during central nervous system development. OMG encodes for an inhibitor of
      neurite outgrowth by the binding to the Nogo-66 receptor (RTN4R). CDK5R1 and OMG
      genes are characterized by large 3' and 5' untranslated regions (UTRs), where we
      predict the presence of several transcription/translation regulatory elements. We
      screened 100 unrelated Italian patients affected by unspecific MR for mutations
      in CDK5R1 and OMG coding regions and in their 3' or 5' UTRs. Four novel mutations
      and two novel polymorphisms for CDK5R1 and three novel mutations for OMG were
      detected, including two missense changes (c.323C>T; A108V in CDK5R1 and
      c.1222A>G; T408A in OMG), one synonymous codon variant (c.532C>T; L178L in
      CDK5R1), four variants in CDK5R1 3'UTR and two changes in OMG 5'UTR. All the
      mutations were absent in 370 chromosomes from normal subjects. The allelic
      frequencies of the two novel polymorphisms in CDK5R1 3'UTR were established in
      both 185 normal and 100 mentally retarded subjects. Prediction of mRNA and
      protein secondary structures revealed that two changes lead to putative
      structural alterations in the mutated c.2254C>G CDK5R1 3'UTR and in OMG T408A
      gene product.

PMID- 16425043
TI  - Landscape mosaic induces traveling waves of insect outbreaks.
AB  - The effect of landscape mosaic on recurrent traveling waves in spatial population
      dynamics was studied via simulation modeling across a theoretical landscape with
      varying levels of connectivity. Phase angle analysis was used to identify
      locations of wave epicenters on patchy landscapes. Simulations of a tri-trophic
      model of the larch budmoth (Zeiraphera diniana) with cyclic population dynamics
      on landscapes with a single focus of high-density habitat produced traveling
      waves generally radiating outwardly from single and multiple foci and spreading
      to isolated habitats. We have proposed two hypotheses for this result: (1)
      immigration subsidies inflate population growth rates in the high connectivity
      habitat and, thus, reduce the time from valleys to peaks in population cycles;
      (2) populations in the high connectivity habitat crash from peaks to valleys
      faster than in an isolated habitat due to over-compensatory density dependence.
      While population growth rates in the high connectivity habitat benefitted from
      immigration subsidies, times from population valleys to peaks were greater in
      high connectivity habitat due to a greater magnitude of fluctuations. Conversely,
      the mean time of the crash from population peaks to valleys was shorter in high
      connectivity habitat, supporting the second hypothesis. Results of this study
      suggest over-compensatory density dependence as an underlying mechanism for
      recurrent traveling waves originating in high connectivity habitats aggregated
      around a single focus.

PMID- 16425044
TI  - Sex, sex-ratios, and the dynamics of pelagic copepod populations.
AB  - I examine how the population biology of pelagic copepods depends on their mating
      biology using field data and a simple demographic model. Among calanoid copepods,
      two distinct patterns emerge. First, copepods that lack seminal receptacle and
      require repeated mating to stay fertilized have near equal adult sex ratios in
      field populations. Winter population densities are orders of magnitude less than
      the critical population density required for population persistence, but
      populations survive winter seasons as resting eggs in the sediment. Population
      growth in these species is potentially high because they have on average a factor
      of 2 higher egg production rates than other pelagic copepods. Second, other
      copepods require only one mating to stay fertile, and populations of these
      species have strongly female-skewed adult sex-ratios in field populations.
      Resting eggs have not been described within this group. Winter population sizes
      are well predicted by the critical density required for population persistence
      which, in turn, is closely related to the body-size-dependent mate-search
      capacity. Thus, the different requirements for mating lead in the first case to a
      more opportunistic reproductive strategy that implies rapid colonization of the
      pelagic during productive seasons, and in the second case to a strategy that
      allows maintenance of a pelagic populations during unproductive seasons. Positive
      density dependent population growth during periods of low population density
      ('Allee effect') amplifies population density variation during winter into the
      subsequent summer, thus explaining why summer densities appear to depend more on
      winter densities than on current growth opportunities in pelagic copepods.

PMID- 16425045
TI  - Ectoparasites and age-dependent survival in a desert rodent.
AB  - Host age is one of the key factors in host-parasite relationships as it possibly
      affects infestation levels, parasite-induced mortality of a host, and parasite
      distribution among host individuals. We tested two alternative hypotheses about
      infestation pattern and survival under parasitism in relation to host age. The
      first hypothesis assumes that parasites are recruited faster than they die and,
      thus, suggests that adult hosts will show higher infestation levels than
      juveniles because the former have more time to accumulate parasites. The second
      hypothesis assumes that parasites die faster than they are recruited and, thus,
      suggests that adults will show lower infestation levels because of acquired
      immune response and/or the mortality of heavily infested juveniles and, thus,
      selection for less infested adults. As the negative effects of parasites on host
      are often intensity-dependent, we expected that the age-related differences in
      infestation may be translated to lower or higher survival under parasitism of
      adults, in the cases of the first and the second hypotheses, respectively. We
      manipulated ectoparasite numbers using insecticide and assessed the infestation
      pattern in adult and juvenile gerbils (Gerbillus andersoni) in the Negev Desert.
      We found only a partial support for age-dependent parasitism. No age-related
      differences in infestation and distribution among host individuals were found
      after adjusting the ectoparasite numbers to the host's surface area. However, age
      related differences in survival under parasitism were revealed. The survival
      probability of parasitized juveniles decreased in about 48% compared to
      unparasitized hosts while the survival probability of adults was not affected by
      ectoparasites. Our results suggest that the effect of host age on host-parasite
      dynamics may not explicitly be determined by age-dependent differences in
      ectoparasite recruitment or mortality processes but may also be affected by other
      host-related and parasite-related traits.

PMID- 16425046
TI  - Spatial heterogeneity in predator activity, nest survivorship, and nest-site
      selection in two forest thrushes.
AB  - The ability of prey to find and use predator-free space has far-reaching
      consequences for their persistence and interactions with their predators. We
      tested whether nest survivorship of the ground-nesting veery (Catharus
      fuscescens) and shrub-nesting wood thrush (Hylocichla mustelina) was related to
      the local absence of a major nest predator, the white-footed mouse (Peromyscus
      leucopus). Mouse-free space was defined by trap stations that failed to trap a
      mouse during the avian breeding season (approximately May through July). In
      addition, mouse activity was quantified at individual trap stations based on the
      number of captures during the same period (six 2.25-ha trapping grids, each
      containing 121 trap stations trapped repeatedly throughout the summer between
      1998 and 2002.) Annual mouse-free space was correlated with other measures of
      mouse activity based on trapping data. Both mouse-free space and activity metrics
      were significantly related to annual rates of nest predation (i.e., nest daily
      mortality rate) in veery but not wood thrush. Likewise, mouse-free space and
      mouse activity within the nest neighborhood (approximately 30x30 m2 surrounding
      each nest) was significantly related to nest survivorship in veery but not wood
      thrush. More trap stations had consistently greater (hotspots) and lesser
      (coldspots) mouse activity than expected by chance, and veeries were
      significantly more likely to nest near stations that had below the grid-average
      trapping success. Our study thus documented significant spatial variability in
      predator activity and its relationship to nest predation and nest-site selection
      in a ground-nesting songbird.

PMID- 16425047
TI  - Richness and species composition of arboreal arthropods affected by nutrients and
      predators: a press experiment.
AB  - A longstanding goal for ecologists is to understand the processes that maintain
      biological diversity in communities, yet few studies have investigated the
      combined effects of predators and resources on biodiversity in natural
      ecosystems. We fertilized nutrient limited plots and excluded insectivorous birds
      in a randomized block design, and examined the impacts on arthropods associated
      with the dominant tree in the Hawaiian Islands, Metrosideros polymorpha
      (Myrtaceae). After 33 months, the species load (per foliage mass) of herbivores
      and carnivores increased with fertilization, but rarified richness (standardized
      to abundance) did not change. Fertilization depressed species richness of
      arboreal detritivores, and carnivore richness dropped in caged, unfertilized
      plots, both because of the increased dominance of common, introduced species with
      treatments. Herbivore species abundance distributions were more equitable than
      other trophic levels following treatments, and fertilization added specialized
      native species without changing relativized species richness. Overall, bird
      removal and nutrient addition treatments on arthropod richness acted largely
      independently, but with countervailing influences that obscured distinct top-down
      and bottom-up effects on different trophic levels. This study demonstrates that
      species composition, biological invasions, and the individuality of species
      traits may complicate efforts to predict the interactive effects of resources and
      predation on species diversity in food webs.

PMID- 16425048
TI  - Combined food and predator effects on songbird nest survival and annual
      reproductive success: results from a bi-factorial experiment.
AB  - Food and predators have traditionally been viewed as mutually exclusive
      alternatives when considering factors affecting animal populations. This has led
      to long controversies such as whether annual reproductive success in songbirds is
      primarily a function of food-restricted production or predator-induced loss.
      Recent studies on both birds and mammals suggest many of these controversies may
      be resolved by considering the combined effects of food and predators. We
      conducted a 2x2 manipulative food addition plus natural predator reduction
      experiment on song sparrows (Melospiza melodia) over three consecutive breeding
      seasons. Food and predators together affected partial clutch or brood loss, nest
      survival (total clutch or brood loss) and annual reproductive success. When
      combined, our two treatments reduced partial losses by more than expected if the
      effects of food and predators were independent and additive. Food and predators
      also interacted in their effects on nest survival since food addition
      significantly reduced the rate of nest predation. While annual reproductive
      success was highly correlated with nest predation (r2=0.71) the strength of this
      relationship was reinforced by the indirect effects of food addition on nest
      predation. A stepwise multiple regression showed that the residual variation in
      annual reproductive success was explained by food effects on the total number of
      eggs laid over the season and the combined effects of food and predators on
      partial losses noted above. We conclude that annual reproductive success in song
      sparrows is a function of both food-restricted production and predator-induced
      loss and indirect food and predator effects on both clutch and brood loss. We
      highlight the parallels between our results and those from a comparable bi
      factorial experiment on mammals because we suspect combined food and predator
      effects are likely the norm in both birds and mammals.

PMID- 16425049
TI  - Composition of speciose leaf litter alters stream detritivore growth, feeding
      activity and leaf breakdown.
AB  - Leaf litter derived from riparian trees can control secondary production of
      detritivores in forested streams. Species-rich assemblages of leaf litter reflect
      riparian plant species richness and represent a heterogeneous resource for stream
      consumers. Such variation in resource quality may alter consumer growth and thus
      the feedback on leaf breakdown rate via changes in feeding activity. To assess
      the consequences of this type of resource heterogeneity on both consumer growth
      and subsequent litter breakdown, we performed a laboratory experiment where we
      offered a leaf-shredding stream detritivore (the stonefly Tallaperla maria,
      Peltoperlidae) ten treatments of either single- or mixed-species leaf litter. We
      measured consumer growth rate, breakdown rate and feeding activity both with and
      without consumers for each treatment and showed that all three variables
      responded to speciose leaf litter. However, the number of leaf species was not
      responsible for these results, but leaf species composition explained the
      apparent non-additive effects. T. maria growth responded both positively and
      negatively to litter composition, and growth on mixed-litter could not always be
      predicted by averaging estimates of growth in single-species treatments.
      Furthermore, breakdown and feeding rates in mixed litter treatments could not
      always be predicted from estimates of single-species rates. Given that species
      richness and composition of senesced leaves in streams reflects riparian plant
      species richness, in-stream secondary production of detritivores and organic
      matter dynamics may be related to species loss of trees in the riparian zone.
      Loss of key species may be more critical to maintaining such processes than
      species richness per se.

PMID- 16425050
TI  - [A new questionnaire for recognizing cognitive problems in children and
      adolescents].
AB  - BACKGROUND: Patients with psychiatric or neurologic disease often suffer from
      neuropsychologic problems. The purpose of this study was to present a parental
      questionnaire (KOPKIJ) that assesses neuropsychologic problems in children and
      adolescents between 6 and 16 years of age. METHODS: We tested theoretical
      analysis, standardization, and validation of the questionnaire in 352 healthy
      controls and 116 pediatric patients with epilepsy. RESULTS: The objectivity of
      this standardized questionnaire can be considered high, and the reliability of
      the subscales is satisfying. Epileptic patients had higher scores than healthy
      controls, and the validation displayed reasonable connections with clinical
      factors and the results of neuropsychological evaluation. CONCLUSION: The KOPKIJ
      allows an orientating appraisal clear picture of cognitive problems of children
      and adolescents at home and at school, simplifies anamnesis, and eases the
      planning of therapy strategies.

PMID- 16425051
TI  - [Eagle's syndrome: a rare cause of facial pain and difficulties in swallowing].
AB  - A 47-year-old patient suffered from right-sided facial pain in the chin and lower
      cheek, hyperpathia, and difficulties in swallowing. The diagnosis of Eagle's
      syndrome was based on digital palpation of the bilaterally elongated styloid
      process and radiography. Eagle's syndrome should be considered in patients with
      difficulty swallowing, masticatory pain, globus sensation, and neuropathic
      pharyngeal or facial pain. If conservative therapy fails, selected patients may
      benefit from surgical excision of elongated styloid processes if pain relief by
      local anesthesia is proven.

PMID- 16425052
TI  - [Experience with new teaching methods and testing in psychiatric training].
AB  - In 1999, the Charite Medical University in Berlin, Germany, implemented a
      reformed medical study course (RMSC) along with traditional undergraduate medical
      education. The RMSC is characterized by problem-based learning (PBL), training in
      communication skills with "simulated patients", and interdisciplinary seminars.
      The curriculum is organized into blocks according to organ system and age (period
      od life). In a new intensive 4-week psychiatric block, 4th-year students get
      practical experience in psychiatric wards. Furthermore, PBL groups and workshops
      are offered that focus on frequent psychiatric disorders. By providing
      interactive courses with simulated patients, students are intensively trained in
      taking psychiatric histories and in generating psychopathological findings.
      Defined learning objectives are tested using multiple-choice items and
      objectively structured clinical examinations at semester end. First positive
      results indicate that this course represents an appropriate and practicable
      curriculum for teaching psychiatry in Germany.

PMID- 16425054
TI  - [The role of psychoeducation in the treatment of psychiatric inpatients].
AB  - Psychoeducation has proved to be a highly effective therapeutic method to reduce
      relapse and rehospitalization rates of schizophrenic patients. Education about
      their disease has good results on clinical course and especially on compliance.
      Despite evidence of effectiveness and the recommendations of evidence-based
      guidelines, psychoeducational programs are underutilized in clinical practice.
      Based on a review of the literature, we summarize the development and current
      state of research on psychoeducation. With regard to its broader use in
      psychiatric inpatient treatment, we examine potential barriers and possible
      improvements. Characteristics of a psychoeducational concept that meets the
      demands of the modern structure of psychiatric institutions are discussed.
      Essential issues are specificity in the traditional diagnosis of schizophrenia
      and applying integrative concepts to the mainly didactic method used today.

PMID- 16425053
TI  - [New developments in the pharmacotherapy of cocaine dependence].
AB  - New possibilities with medications for the treatment of cocaine dependence have
      begun to emerge. For example, in a randomised controlled study, disulfiram
      succeeded for the first time in significantly reducing cocaine consumption. In
      October 2003, a phase IIb study was started in the USA testing active
      immunisation against cocaine dependence. There is also an ongoing study in
      Switzerland testing methylphenidate treatment in combination with cognitive
      behavioural therapy. Pilot studies indicate that vigabatrin, selegiline, and
      topiramate are promising candidates for further clinical substance testing.

PMID- 16425055
TI  - [Extragenital endometriosis leading to piriformis syndrome].
AB  - We report on a 44-year-old woman with a history of sciatica fluctuating with her
      menstrual cycle and going back over 10 years; ultimately it was present
      continuously and became disabling. Over the years the patient developed
      ipsilateral foot-drop, a sensory disorder in the lateral aspect of the lower limb
      and back of the foot, and atrophy of the gluteus muscle. MRI confirmed the
      suspicion of extragenital endometriosis, which had caused piriformis syndrome by
      compression with consequent damage to the sciatic and inferior gluteal nerves.
      After hormonal therapy had been tried without success, the endometrioma was
      excised to relieve the pressure on the nerves, and the diagnosis was confirmed
      histopathologically. The motor deficit remained up to the 15 months since
      surgery, but the patient is now free of pain.

PMID- 16425056
TI  - Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation
      upon long-term continuous infusion in critically ill patients.
AB  - OBJECTIVE: The objective of the present investigation was to develop a population
      pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long
      term continuous infusion in critically ill patients. METHODS: The study was
      conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam
      by continuous infusion for at least 24 h. Repeated blood samples were obtained
      for determination of the concentrations of lorazepam and midazolam. The level of
      sedation was assessed using a 5-point sedation scale. RESULTS: The
      pharmacokinetics of lorazepam and midazolam was described with previously
      proposed pharmacokinetic models. For the pharmacodynamics, the probability that
      the sedation was equal to or more than a specific score was described using a
      sigmoid E(max) model. The EC(50) values of lorazepam for the sedation scores
      equal or larger than 2-5 were 6.1, 57, 184 and 529 ng/ml, respectively. The
      corresponding values for midazolam were 216, 483, 1,100 and 2,200 ng/ml. Inter
      individual variability in the EC(50) values was relatively high with a CV of 68%
      for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of
      the observed inter-individual variability were identified. CONCLUSION: The
      population pharmacodynamic model shows a similarly wide intra- and inter
      individual variability in the pharmacodynamics of both lorazepam and midazolam.
      Thus, the previously observed differences in "ease of titration" between
      lorazepam and midazolam are unrelated to pharmacodynamic factors.

PMID- 16425057
TI  - [Desmoplastic neurotropic melanoma. Diagnosis and therapeutic procedures for a
      rare clinical entity].
AB  - Desmoplastic neurotropic melanoma is an exceedingly rare variant of the malignant
      melanomas. Since the initial description, only about 500 cases have been reported
      in the literature. These melanomas mostly occur on the head, neck, and face, and
      a wide local excision of the tumor is probably the most important prognostic
      factor. Therefore, in most cases the tumor resections result in large tissue
      defects. To gain a good cosmetic result, tissue movement using flaps or grafts
      will most likely be required to cover the defect. In this paper, a 79-year-old
      patient with a basal cell carcinoma and desmoplastic melanoma on the scalp is
      described, and the therapeutic procedure is discussed.

PMID- 16425058
TI  - Rewarding properties of sildenafil citrate in mice: role of the nitric oxide
      cyclic GMP pathway.
AB  - RATIONALE: Sildenafil citrate is widely prescribed for erectile dysfunction and
      acts by inhibiting phosphodiesterase type-5, resulting in accumulation of cyclic
      guanosine monophosphate (cGMP) via activation of nitric oxide synthase (NOS). The
      nitric oxide (NO) system is relevant to the rewarding effects of various drugs of
      abuse. Several epidemiologic studies indicate that sildenafil is abused in a
      recreational fashion. OBJECTIVES: In the present study, the rewarding properties
      of sildenafil and probable involvement of the NO-cGMP pathway were investigated
      in adult male NMRI mice. METHODS: The ability of sildenafil citrate (1-40 mg/kg)
      to produce conditioned place preference (CPP) was studied in an unbiased CPP
      paradigm. The effects of NO precursor L-arginine, nonselective NOS inhibitor N(G)
      nitro-L-arginine methyl ester (L-NAME), and the inhibitor of guanylyl cyclase
      methylene blue (MB) on sildenafil-induced CPP were assessed. RESULTS: Mice that
      received sildenafil (20 and 40 mg/kg) in one environment during conditioning
      phase displayed a preference for this environment. Both L-NAME (5 mg/kg) and MB
      (1 mg/kg) in combination with sildenafil (20 mg/kg) suppressed the acquisition of
      sildenafil-induced place preference. Lower and per se noneffective dose of
      sildenafil (10 mg/kg) and L-arginine (60 mg/kg), when coadministered, exerted a
      significant place conditioning. CONCLUSIONS: Sildenafil shows rewarding
      properties that may involve the NO-cGMP pathway.

PMID- 16425059
TI  - Effects of memantine, haloperidol, and cocaine on primary and conditioned
      reinforcement associated with cocaine in rhesus monkeys.
AB  - RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been implicated in
      mediating the reinforcing effects of abused drugs. Some reports indicate the
      uncompetitive NMDA antagonist, memantine, modulates the conditioned and
      unconditioned effects of stimulants in rats. OBJECTIVE: The objective of this
      study was to evaluate the effects of memantine on the primary and conditioned
      reinforcing effects of cocaine in the rhesus monkey. METHODS: Rhesus monkeys were
      trained to press levers reinforced with either cocaine-associated stimuli (brief
      stimuli, BS) or 30-microg/kg cocaine infusion during daily, 75-min experimental
      sessions in which the reinforcers were independently available in separate
      components according to identical progressive ratio (PR) schedules. Memantine
      (0.3-10 mg/kg), and as comparators, haloperidol (0.001-0.1 mg/kg) and cocaine
      (0.01-1 mg/kg), were administered 5 min before experimental sessions. RESULTS:
      Memantine (0.3-3 mg/kg) produced decreases in responding maintained by BS
      presentations at some doses which failed to affect cocaine self-administration
      when measured during equivalent periods early in the experimental session.
      Memantine (3 mg/kg) increased cocaine self-administration, however, later in the
      session. A low dose of haloperidol (0.001 mg/kg) increased the number of BS
      presentations, whereas higher doses decreased their number. Cocaine self
      administration was not significantly affected by haloperidol until a behaviorally
      suppressant dose (0.1 mg/kg) was administered. Pretreatment with high doses of
      cocaine (0.3 and 1 mg/kg) decreased responding maintained by both reinforcers.
      CONCLUSION: These results suggest that while memantine may attenuate the
      conditioned reinforcing effects of cocaine-associated stimuli, it may also
      occasion increase levels of cocaine self-administration. These findings support
      the hypothesis that the NMDA receptor can play a role in modulating the
      conditioned and primary reinforcing effects of cocaine.

PMID- 16425061
TI  - The effects of exogenous interleukin-4 on hypoxia-induced lung injury.
AB  - The aim of this study was to determine the effects of recombinant human
      interleukin-4 (rhIL-4) on hypoxia-induced lung injury in immature rats. The study
      was performed on 1-day-old Sprague Dawley rat pups. Group 1 (n = 7) served as
      nonhypoxic controls. Group 2 (untreated, n = 7) rats were subjected to hypoxia
      reoxygenation (H/O) and were then returned to their mothers. Group 3 (rhIL-4
      treated, n = 7) rats were subjected to H/O, were returned to their mothers, and
      were treated with rhIL-4 (75 microg/kg subcutaneously) for the next 3 days. All
      animals were killed on day 4 and lung specimens were obtained to determine the
      tissue level of malondialdehyde (MDA) and histological changes. In the untreated
      group, MDA levels were significantly increased compared to control and rhIL-4
      groups. In the rhIL-4 treated group, MDA levels were not significantly different
      compared to control group. The rhIL-4 treated group had a significantly lower
      score of pathological lesions and alveolar hemorrhage grade values than the
      untreated group. The untreated animals had areas marked intraalveolar hemorrhage,
      capillary congestion, interstitial edema, and hypercellularity of lung that were
      not seen in the rhIL-4 treated rats. In conclusion, this study found beneficial
      effects of rhIL-4 in an experimental model on the hypoxia-induced lung injury.

PMID- 16425060
TI  - Elevated impulsivity and impaired decision-making cognition in heavy users of
      MDMA ("Ecstasy").
AB  - RATIONALE: In animal studies, the common club drug 3,4
      methylendioxymethamphetamine (MDMA, "Ecstasy") consistently caused a prolonged
      loss of presynaptic serotonergic neurons, and evidence suggests that MDMA
      consumption may also affect the human serotonergic system. Serotonin (5-HT) has
      been implicated in the regulation of impulsivity and such executive functions as
      decision-making cognition. In fact, MDMA users have shown elevated impulsivity in
      two studies, but little is known about decision making in drug-free MDMA
      consumers. OBJECTIVE: The aim of this study was to examine the cognitive
      neurotoxicity of MDMA with regard to behavioral impulsivity and decision-making
      cognition. METHODS: Nineteen male, abstinent, heavy MDMA users; 19 male,
      abstinent cannabis users; and 19 male, drug-naive controls were examined with the
      Matching Familiar Figures Test (MFFT) as well as with a Go/No-Go Task (GNG) for
      impulsivity and with a Gambling Task (GT) for executive functioning. RESULTS:
      MDMA users showed significantly elevated impulsivity in the MFFT Impulsivity
      score (I-score), but not in commission errors of the GNG, compared with controls.
      Cannabis users did not yield altered impulsivity compared with controls. In the
      GT, MDMA users performed significantly worse than cannabis consumers and
      controls, whereas cannabis users exhibited the same decision-making capacity as
      controls. In addition, the I-score as well as the decision-making performance was
      correlated with measures of MDMA intake. The I-score and the decision-making
      performance were also correlated. CONCLUSION: These results suggest that heavy
      use of MDMA may elevate behavioral impulsivity and impair decision-making
      cognition possibly mediated by a selective impairment of the 5-HT system.

PMID- 16425063
TI  - Associative visual learning, color discrimination, and chromatic adaptation in
      the harnessed honeybee Apis mellifera L.
AB  - We studied associative visual learning in harnessed honeybees trained with
      monochromatic lights associated with a reward of sucrose solution delivered to
      the antennae and proboscis, to elicit the proboscis extension reflex (PER). We
      demonstrated five properties of visual learning under these conditions. First,
      antennae deprivation significantly increased visual acquisition, suggesting that
      sensory input from the antennae interferes with visual learning. Second, covering
      the compound eyes with silver paste significantly decreased visual acquisition,
      while covering the ocelli did not. Third, there was no significant difference in
      the visual acquisition between nurse bees, guard bees, and foragers. Fourth, bees
      conditioned with a 540-nm light stimulus exhibited light-induced PER with a 618
      nm, but not with a 439-nm light stimulus. Finally, bees conditioned with a 540-nm
      light stimulus exhibited PER immediately after the 439-nm light was turned off,
      suggesting that the bees reacted to an afterimage induced by prior adaptation to
      the 439-nm light that might be similar to the 540-nm light.

PMID- 16425062
TI  - Distribution and function of potassium channels in the electrosensory lateral
      line lobe of weakly electric apteronotid fish.
AB  - Potassium channels are one of the fundamental requirements for the generation of
      action potentials in the nervous system, and their characteristics shape the
      output of neurons in response to synaptic input. We review here the distribution
      and function of a high-threshold potassium channel (Kv3.3) in the electrosensory
      lateral line lobe of the weakly electric fish Apteronotus leptorhynchus, with
      particular focus on the pyramidal cells in this brain structure. These cells
      contain both high-threshold Kv3.3 channels, as well as low-threshold potassium
      channels of unknown molecular identity. Kv3.3 potassium channels regulate burst
      discharge in pyramidal cells and enable sustained high frequency firing through
      their ability to reduce an accumulation of low-threshold potassium current.

PMID- 16425064
TI  - Oregano (Lippia spp.) kills Giardia intestinalis trophozoites in vitro:
      antigiardiasic activity and ultrastructural damage.
AB  - In the world, giardiosis is still a very important parasitic disease; only in
      Asia, Africa and America, there are more than 200 million of infected people in a
      year. The usual treatments are drugs that produce undesirable secondary effects,
      perhaps favouring the resistant strain selection. One alternative is to research
      compounds from plants used as antidiarrhoeic or antiparasitic in the traditional
      medicine. In a previous work, we found that Lippia beriandieri (Oregano) revealed
      to be more potent than tinidazole, a common antigiardiasic drug. In this current
      work, we tested the cell viability by re-culture and reduction of MTT-tetrazolium
      salts to MTT-formazan, and we showed the effect of oregano ethanolic extracts
      against Giardia intestinalis (synonyms: Giardia duodenalis, Giardia lamblia)
      trophozoites at concentrations ranging form 58 to 588 microg. We demonstrated the
      ultrastructural injury produced by oregano extracts in this parasite.
      Trophozoites lost their size and shape and showed damage in nucleus structure,
      perhaps by breaking the pattern of nucleoskeleton proteins.

PMID- 16425065
TI  - Patients with papular urticaria have IgG antibodies to bedbug (Cimex lectularius)
      antigens.
AB  - IgG and IgE against salivary gland proteins of bedbug (Cimex lectularius) were
      assessed in comparison with mosquito (Culex pipiens) and flea (Pulex irritans)
      antigens in the sera of papular urticaria patients (group I), siblings without
      papular urticaria (group IIa), patients' parents (group IIb), and healthy
      controls (group III) (Immunoblotting). Anti-C. lectularius IgG was significantly
      recognized at 66 and 10 kDa in 40% of group I, besides others ranging from 45 to
      107 kDa. Group IIa significantly reacted with 70 kDa (57.1%). Group IIb reacted
      with 21 and 8.5 kDa (26.7%). Sixty percent of group IIb and 100% of group III
      significantly identified a band of 12.5 kDa. IgG against C. pipiens was
      significantly recognized at a range of 18-105 kDa in group I, IIb (115, 7 kDa),
      and III (58, 50 kDa). Anti-P. irritans IgG was significantly recognized by group
      I (100, 70 kDa) and group IIa (60, 35 kDa). IgE response was confined to C.
      pipiens at 115 and 54 kDa in groups I and III, respectively, besides 68 and 58
      kDa in group IIa. It is concluded that IgG is present against C. lectularius, C.
      pipiens, and P. irritans in papular urticaria and may contribute to its
      pathogenesis.

PMID- 16425066
TI  - Seroprevalence of Neospora caninum and Toxoplasma gondii in camels (Camelus
      dromedarius) in Mashhad, Iran.
AB  - One hundred twenty camels were blood-sampled and used to evaluate serological
      screening for Neospora caninum and Toxoplasma gondii infection by indirect
      fluorescent antibody test (IFAT) in Mashhad, Iran, during years 2004-2005. Of the
      120 camels, antibodies to N. caninum were found in three in titers of 1:20 and in
      four in titers of 1:40 using whole N. caninum tachyzoites as IFAT slide (VMRD
      Inc., Pullman, WA 99163, USA). Antibodies to T. gondii were found in three camels
      in titers 1:20 and in two camels in titers 1:40 using whole T. gondii tachyzoites
      as IFAT slide (BIOGENE, Iran).

PMID- 16425067
TI  - Development of a recombinant indirect ELISA for the diagnosis of Theileria sp.
      (China) infection in small ruminants.
AB  - Theileria sp. (China) causes severe limitations on the development of the
      livestock industry in the north-west of China. An enzyme-linked immunosorbent
      assay (ELISA) based on merozoite homogenate of the parasite for diagnosis of
      infection has been established; however, cross-reactivity with other small
      ruminant-infecting piroplasms could not be excluded. Thus, a prerequisite for
      epidemiological surveys and diagnosis was the establishment of a recombinant
      protein-based ELISA. To this end, serum from Theileria sp. (China)-infected sheep
      was used to screen a Theileria lestoquardi expression library, resulting in the
      identification of a specifically reacting clone with a high identity to the heat
      shock protein 70 (HSP70) of Theileria parva and Theileria annulata and thus named
      TlHSP70. An HSP70 homologue was also confirmed to be expressed by Theileria sp.
      (China) merozoites (TcHSP70). A part of the TlHSP70 protein, found to be
      conserved in TcHSP70, was recombinantly expressed and used to establish an ELISA.
      A total of 260 field serum samples tested resulted in a sensitivity and
      specificity of 94.3 and 89.5%, respectively, in comparison with the merozoite
      homogenate ELISA. The potentials of the application of the test in
      epidemiological surveys to map out the prevalence of the disease and for routine
      diagnostics are described.

PMID- 16425068
TI  - [Therapy-resistant cutaneous infiltrates in chronic lymphocytic leukemia].
AB  - Chronic lymphocytic leukemia (CLL) is a low-grade B-cell non-Hodgkin lymphoma.
      Skin involvement is observed in up to 25% of patients. A 70-year-old men with
      presented with prominent erythematous facial infiltrates. After the diagnosis of
      CLL was established, he showed a good hematologic response to the monoclonal
      antibody rituximab, but the skin infiltrates were therapy-resistant.

PMID- 16425069
TI  - [Successful therapy of a rheumatoid leg ulcer with intravenous immunoglobulins].
AB  - Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Leg ulcers
      in rheumatoid arthritis may be caused by vasculitis and are an interdisciplinary
      therapeutic challenge. A 69 year old women with rheumatoid arthritis and many
      other medical problems presented with widespread vasculitis-induced therapy
      resistant ulceration on her right lower leg. Since previous therapeutic efforts
      had a negative effect on wound healing, we administered intravenous
      immunoglobulins which led to complete healing of the ulcer was achieved. Both the
      serological and rheumatologic features of her rheumatoid arthritis also improved.
      Intravenous immunoglobulins represented an effective therapeutic option with
      fewer side effects in the therapy of vasculitis-induced leg ulceration in this
      patient with rheumatoid arthritis.

PMID- 16425071
TI  - Outcome and treatment strategy for mid- and lower-thoracic esophageal cancer
      recurring locally in the lymph nodes of the neck.
AB  - The aim of the present study was to assess the outcome of treatment for patients
      with recurrent mid- and lower-thoracic esophageal cancers in whom recurrence was
      localized to the lymph nodes of the neck, and to determine the best strategy for
      further treatment. Between 1989 and 2001, 270 patients with mid- and lower
      thoracic esophageal cancer underwent curative esophagectomy; 90 of those patients
      had a cancer recurrence. Our focus was on lymph node recurrence, especially when
      the recurrent cancers were localized to the lymph nodes in the neck. The outcomes
      of those patients and the efficacy of the strategies used to treat the recurrent
      cancers were determined. In 43 patients (48%), recurrent cancer initially
      appeared in the lymph nodes. Among the 43 patients, 15 (35%) had localized neck
      recurrence. The time between tumor recurrence and death among the 15 patients
      with localized neck recurrence was significantly longer than among the 28
      patients with other recurrence patterns. In addition, 15 patients underwent lymph
      node resection, while 28 patients were treated non-surgically. The time between
      tumor recurrence and death was significantly longer in patients treated
      surgically. Of the 15 patients in whom recurrence affected the neck lymph nodes
      only, 10 (67%) were treated surgically; their 2-year survival rate after
      recurrence was 45%. The outcomes of recurrent esophageal cancers localized to the
      lymph nodes of the neck were better than those seen with other recurrence
      patterns, and salvage resection followed by chemoradiation therapy would seem to
      be indicated for those patients.

PMID- 16425072
TI  - Surgical treatment of complex malignant anterior mediastinal tumors invading the
      superior vena cava.
AB  - Determining the appropriate surgery-based treatment for complicated anterior
      mediastinal malignancies (CAMM), especially those invading the superior vena cava
      (SVC) and its branches, remains a challenge for general thoracic surgeons. In
      this report, we summarize our experience and lessons regarding this issue in
      order to discuss a reasonable strategy for diagnosis and treatment of CAMM.
      Between January 2001 and April 2003, 15 patients with CAMM invading the SVC
      and/or its branches with or without invasion of other neighboring organs were
      surgically treated in our institution by a single surgeon team. We collected
      clinical data from the medical charts and from surgeons' specific notes for
      complicated cases, and performed a comprehensive analysis. There were 9 patients
      with malignant thymoma. Thymic carcinoma, teratoma, embryonal carcinoma,
      Hodgkin's lymphoma, non-Hodgkin's lymphoma, and mixed teratoma with thymoma were
      diagnosed in 1 patient each. All procedures were performed via median sternotomy.
      Some angioplasty techniques were successfully used to resect and reconstruct the
      SVC. Ten of the 15 patients also underwent pulmonary resection due to involvement
      of pulmonary parenchyma. Four of the patients underwent perioperative
      chemotherapy. There were no perioperative deaths. Two patients suffered prolonged
      ventilation after surgery, and there were no other severe complications related
      to surgery. One patient died 10 months after surgery. The remaining 14 patients
      were still living and their progress is still monitored. As of August 2004, the
      median follow-up duration for all patients was 35 months, and the disease-free
      survival duration was 10-43 months. CAMM can be safely and completely resected
      via a median sternotomy, even if it has invaded other mediastinal structures.
      CAMM should be pathologically identified before initial treatment. A good outcome
      for patients with CAMM is possible if a suitable strategy combining accurate
      diagnosis and appropriate treatment, especially surgical resection, is
      established.

PMID- 16425073
TI  - Effects of mosapride citrate on patients after vagal nerve preserving distal
      gastrectomy reconstructed by interposition of a jejunal J pouch with a jejunal
      conduit for early gastric cancer.
AB  - BACKGROUND: Vagal nerve-preserving distal gastrectomy reconstructed by
      interposition of a jejunal J pouch with a jejunal conduit (hereinafter called
      DGP) is a function-preserving operation for early gastric cancer. However, some
      patients after DGP have suffered from postprandial stasis in the substitute
      stomach, and postprandial stasis leads to abdominal symptoms. To clarify the
      significance of mosapride citrate (MS) for prevention of food stasis in the
      substitute stomach for patients after DGP, we studied the effects of MS before
      and after administration of MS. MATERIALS AND METHODS: In a total of 18 patients
      (10 men, 8 women; aged 34 to 70 years, average 63.1 years) during 5 years after
      DGP for early gastric cancer (Billroth I, D1+alpha lymph node dissection,
      curability A), the relationship between their postoperative quality of life (QOL)
      and emptying function of the substitute stomach (EFS) was compared using a
      radioisotope method before MS therapy and after MS therapy at an oral dose of 15
      mg/day for 3 months. RESULTS: (1) Interview. After MS therapy patients evidently
      had more appetite and ate more, with a slightly increase in body weight (0.5
      approximately 2 kg) compared with patients before MS therapy. Before and after MS
      therapy no patients had early dumping symptoms, and after MS therapy all patients
      clearly had fewer symptoms such as reflux esophagitis, nausea, and abdominal pain
      compared with before MS therapy. After MS therapy they also had significantly
      decreased abdominal fullness compared with before MS therapy (P=0.0026).
      Endoscopically, we found reflux esophagitis in 2 patients from the before MS
      therapy group but in no patients from the after MS therapy group. All patients in
      the before MS therapy group showed residual contents in the substitute stomach,
      and seven patients in the after MS therapy group showed residual contents in the
      substitute stomach (P<0.0001). There was a significant difference between before
      and after MS therapy (P<0.0001). (2) EFS; The time to 50% residual rate of the
      before MS therapy group (80.5+/-16.2 min) was significantly slower than that of
      the after MS therapy patients (65.6+/-9.4 min) (P=0.0091). After MS therapy
      (28.4%+/-5.2%), the residual rates at 120 minutes were significantly decreased
      compared with patients before MS therapy (38.2%+/-5.7%) (P=0.0372). CONCLUSIONS:
      Patients from the after MS therapy group clearly had improved gastric stasis
      compared with the before MS therapy group. These results showed more satisfactory
      QOL in patients after MS therapy. It is possible that MS therapy improves
      abdominal fullness due to the postprandial stasis in the substitute stomach,
      contributing to the improvement of QOL of patients after DGP.

PMID- 16425074
TI  - Identification of prognostic factors associated with early mortality after
      surgical resection for pancreatic cancer--under-analysis of cumulative survival
      curve.
AB  - BACKGROUND: The cumulative survival curve after surgery for advanced pancreatic
      cancer is characterized by a steep downward slope in the early postoperative
      period. The aim of this investigation was to identify the characteristics
      associated with early mortality in patients undergoing pancreatic resection for
      pancreatic cancer. METHODS: Thirty-seven patients with extended radical
      pancreatectomy combined with intraoperative radiation therapy were studied. The
      cumulative survival curve in this series was depicted using the Kaplan-Meier
      method. Assuming that there were two distinct survival curves, below and above
      the breakpoint, each part of the curve was modeled as an exponential
      distribution. Three parameters, the breakpoint, the high hazard rate below the
      breakpoint, and the low hazard rate above the breakpoint were estimated by the
      maximum likelihood method. Prognostic factors associated with early mortality
      after surgery were evaluated using univariate and multivariate Cox proportional
      hazards regression analyses. RESULTS: The breakpoint of the survival curve was
      estimated at 41 months. The short-survival group (SSG) was defined as deceased
      earlier than 41 months after surgery, and included 31 patients (83.8 %). The long
      survival patient group (LSG) consisted of 6 patients who were alive more than 41
      months after surgery. Eighteen SSG patients (58.1 %) died of hepatic metastases,
      whereas no LSG patients died of hepatic metastases. Abdominal pain and/or back
      pain during clinical course was identified by multivariate analysis as a
      prognostic factor for patients undergoing pancreatic resection. CONCLUSIONS: The
      high hazard rate in the early postoperative period was closely linked with death
      due to liver metastases. The preoperative presence of local pain was a prognostic
      factor associated with early mortality.

PMID- 16425075
TI  - Incurable esophageal cancer: patterns of tumor spread and therapeutic
      consequences.
AB  - BACKGROUND: The aim of the study was to determine if the two histologic tumor
      types in esophageal cancer exhibit different behavior at advanced tumour stages
      and require a differentiated therapy. PATIENTS AND METHODS: From November 1997 to
      December 2003, 268 patients presented with esophageal carcinoma. Esophagectomy
      was contraindicated in 88 (32.8%) patients (75 men, 13 women) with a median age
      of 64.7 (42-83) years. Fifty-six (63.6%) had squamous cell carcinoma;
      adenocarcinoma was identified in 31 (35.2%). RESULTS: The causes of incurable
      disease were non-resectable distant metastases in 32 (36.4%) patients, local
      tumor spread in 25 (28.4%), and general operative risk in 19 (21.5%). Surgical
      intervention was contraindicated in 7 patients because of a combination of
      general inoperability and local tumor spread, or the presence of distant
      metastases at the time of diagnosis (4 patients declined to undergo surgery and
      in one patient esophageal resection and reconstruction was technically not
      possible). The incurability rate for squamous cell carcinoma was 44.6% because of
      the presence of local tumor spread, compared to a rate of 12.4% for
      adenocarcinoma. Adenocarcinomas with proven hematogenic metastases were
      characterized by a higher incurability rate (64.5% vs. 21.4%) (P=0.0014). The
      prevalence of technical causes of inoperability or of poor general condition was
      similar in both patient groups (P>0.05). The median 1-year survival rates
      estimated (Kaplan-Meier) were 36.5% for patients with squamous cell carcinoma and
      23.7% for patients with adenocarcinoma (P=0.051). Therapeutic measures had a
      significant influence on the prognosis: patients without tumor-specific therapy
      survived 3.4 (0-24) months; those with radiochemotherapy 10.6 (0-25) months;
      those with radiotherapy 11.0 (0-65) months; and those with chemotherapy 16.5 [0
      16.5] months (log-rank test: P=0.0229). In the multivariate analysis, the
      therapeutic measures (P=0.0126) and tumor localization (P=0.0474) proved
      significant for prognosis, but were not the cause of incurability (P=0.0948).
      CONCLUSIONS: The histologic tumor type does not represent an independent
      prognostic factor in patients with incurable disease. Rather, the prognosis is
      dependent on the suitability of the induction of tumor-specific therapeutic
      measures. These are also recommended in patients with incurable disease after
      consideration of the extent of tumor spread, provided the performance of the
      selected measures is justified by the general condition of the patient and the
      expected prognosis.

PMID- 16425076
TI  - Objective assessment of small bowel anastomosis skill in trainee general surgeons
      and urologists.
AB  - INTRODUCTION: The object of this study was to compare the technical ability of
      general surgery and urology trainees to perform a small bowel anastomosis using a
      life-like bench model. METHODS: Forty subjects were divided into two groups based
      on the stage of their training. Specialist registrars (SpRs) trained for 1 to 3
      years were defined as junior SpRs, and those with 4 to 6 years of training were
      defined as senior SpRs. They were asked to perform a small bowel anastomosis on a
      standard latex model using the same equipment, suture material, and standardized
      instructions. Trainees were assessed by three trained observers based on a global
      rating scale. RESULTS: Interrater reliability was 0.83 for the general surgical
      group and 0.88 for the urology group. The median scores obtained by the junior
      SpRs were lower than those achieved by the senior SpRs, and general surgical
      trainees consistently performed better than their matched urology group. This
      difference reached statistical significance for the senior group. CONCLUSIONS:
      Global rating scores provide a reliable, valid method for assessing technical
      skills between specialties when performing a small bowel anastomosis. We provide
      reasons why general surgeons may be more proficient at this task than urologists.
      These findings have possible application to identifying trainees who need
      additional training and may also provide a mechanism to ensure competence in this
      task.

PMID- 16425077
TI  - Single center review of femoral arteriovenous grafts for hemodialysis.
AB  - INTRODUCTION: It is unclear how to manage high risk hemodialysis patients who
      present with an indwelling catheter. The National Kidney Foundation Practice
      Guidelines urge prompt removal of the catheter, but the guidelines do not
      specifically address the problem of patients whose only option is a femoral
      arteriovenous (AV) graft. METHODS: This study was a retrospective review of all
      patients who underwent femoral AV graft placement for hemodialysis access between
      January 1, 1996 and January 1, 2003 at the University of Michigan Health System
      (UMHS). Graft patency is reported according to the standards developed by the
      Society of Vascular Surgery and the American Association of Vascular Surgeons.
      RESULTS: Thirty patients were identified who had undergone femoral AV graft
      placement. The mean follow-up was 23 months (range 1-75 months). The patients had
      had significant medical co-morbidities and multiple previous access operations
      (mean 3; interquartile range 1-5). The 1-year secondary graft patency rate was
      41%, the 2-year rate was 26%, and the 3-year rate was 21%. Infection was the
      cause of final graft loss in eight patients (50% of the grafts losses, 27% of the
      total grafts placed.) Among those who died (n=14), the mean time from femoral
      graft placement to death was 31.2+/-27.5 months. The patient survival was quite
      low: at 1 year 81%, at 2 years 68%, and at 3 years 54%. CONCLUSIONS: These
      complex patients who have exhausted their upper extremity hemodialysis options do
      poorly following femoral AV graft placement. Consideration should be given to
      long-term catheter-based access in some of these patients.

PMID- 16425079
TI  - Is rectal washout necessary in anterior resection for rectal cancer? A
      prospective clinical study.
AB  - BACKGROUND: Implantation of exfoliated malignant cells has been suggested as a
      possible mechanism of tumor recurrence in colorectal anastomoses that might be
      prevented by cytocidal washout. The aim of our study was to assess whether
      malignant cells are likely to be collected by a circular stapler introduced
      transanally to perform an anastomosis and to observe local recurrences during
      follow-up, with special attention to the washout status of patients. METHODS:
      Between May 1999 and March 2004, 96 patients with carcinoma of the rectum and
      distal sigmoid colon undergoing anterior resection under the care of three
      surgeons (only one of whom routinely performed rectal washout) were prospectively
      studied. While 38 patients had rectal washout with 5% povidone-iodine before
      anastomosis, 58 patients did not. A circular stapler was used for anastomosis,
      and the stapler was immediately rinsed in 100 ml of saline. The fluid was then
      classified as "acellular," "malignant cells identified," or "benign cells
      identified" by pathologists. RESULTS: Malignant cells were collected from the
      circular stapler after use in 3 patients (8%) on whom rectal washout was
      performed and in 2 (3%) patients who did not have rectal washout performed
      (P=0.631). Three patients (8%) in the washout group developed local recurrence,
      and 2 patients (3.4%) in the no-washout group had local recurrence (one was
      anastomotic recurrence) (P=0.338). The median follow-up time was 23 (range: 9-70)
      months. CONCLUSIONS: There were no differences in terms of the number of patients
      who had malignant cells collected from the circular stapler and local recurrence
      rates between the two groups. Although this is not a randomized study and size
      and mean follow-up time of the study were not sufficient, our results did not
      offer rational arguments in support of intraoperative rectal washout when a
      circular stapler is used after low anterior resection for carcinoma. Because of
      the limitations of our study, however, we are unable to arrive at a definite
      conclusion regarding rectal washout. There is a need for a randomized,
      controlled, large-scale, multicenter trial to establish the clinical relevance of
      intraoperative rectal washout.

PMID- 16425080
TI  - Rapid intraoperative parathyroid hormone assay--more than just a comfort measure.
AB  - BACKGROUND: Minimally invasive radio-guided parathyroidectomy (MIRP) has been
      embraced as an acceptable therapeutic approach to primary hyperparathyroidism.
      Preoperative sestamibi scanning has facilitated this technique. Here we evaluate
      the addition of a rapid intraoperative parathyroid hormone (iPTH) assay for
      patients undergoing MIRP. METHODS: A series of 51 patients underwent sestamibi
      localization of parathyroid glands followed by MIRP for primary
      hyperparathyroidism. Using peripheral venous samples, iPTH levels were measured
      prior to gland excision, as well as post-excision at 5, 10, and 15 minutes,
      taking a 50% reduction in iPTH level as indicative of complete excision. Next,
      changes in serum iPTH were compared with preoperative and postoperative changes
      in serum calcium, as well as levels of intraoperative ex-vivo radiation counts
      taken by hand-held gamma probe. RESULTS: In this series, a drop of greater than
      50% in iPTH levels was observed in 94% of patients (n=48). Moreover, a
      significant drop in iPTH occurred within 10 minutes of excision in the majority
      (n=42) of cases (P<0.004). Changes in iPTH were comparable with the therapeutic
      reduction in calcium levels, as well as with the change in intraoperative ex-vivo
      gamma counts. CONCLUSIONS: This study demonstrates that the addition of an iPTH
      assay to MIRP provides a quick and reliable intraoperative diagnostic modality in
      confirming correct adenoma removal. Moreover, it precludes the requirement of
      frozen section.

PMID- 16425082
TI  - Perioperative intra-arterial glyceryl trinitrate administration in the prevention
      of radial arterial spasm: does it simplify the construction of arteriovenous
      fistula?

PMID- 16425081
TI  - The effect of esophageal and gastric distension on the crural diaphragm.
AB  - BACKGROUND: The mechanism of prevention of gastric reflux into the esophagus is
      not exactly known. The lower esophagus has a barrier function provided by the
      lower esophageal sphincter. We investigated the hypothesis that the crural
      diaphragm shares in the barrier function not only mechanically but also actively
      through a crural-esophageal-gastric reflex action. METHODS: The study was
      performed during repair of abdominal ventral and incisional hernias in 20
      subjects (11 men, 9 women; age 38.6+/-4.8 years). The electromyographic response
      of the crural diaphragm to individual balloon distension of esophagus and stomach
      was recorded by means of a needle electrode inserted into the crural diaphragm
      and connected to an electromyographic apparatus. The recordings were repeated
      after separate crural, esophageal, and gastric anesthetization. RESULTS: The
      crural diaphragm exhibited basal motor unit action potentials, which decreased on
      esophageal distension (P<0.001) after a mean latency of 17.3+/-2.8 SD ms. The
      crural diaphragm response to esophageal distension did not occur after the crural
      diaphragm or esophagus was anesthetized. Gastric distension effected an increase
      of crural diaphragm electromyographic activity with a mean latency of 18.4+/-4.6
      ms; this effect could not be achieved after the crural diaphragm or stomach was
      anesthetized. CONCLUSIONS: The crural diaphragm has a resting tone that relaxes
      after esophageal distension and contracts after gastric distension. This
      sphincter-like action of the crural diaphragm appears to be a reflex and is
      mediated through the esophagocrural inhibitory and gastrocrural excitatory
      reflexes. The crural diaphragm seems to share actively in the gastroesophageal
      competence mechanism.

PMID- 16425083
TI  - Viability and fertility of human hepatic hydatid cysts.
AB  - INTRODUCTION: The adequate treatment for hydatidosis requires a knowledge of
      certain aspects related to the survival of infectious agents, especially
      protoscoleces. The aim of this study is to evaluate the viability of
      protoscoleces in human hepatic hydatid cysts in order to determine the prevalence
      of their fertility and to study the association with variables typical of the
      host and of the parasite. MATERIALS: A cross-sectional study was done in
      biological material (the fluid from human hepatic hydatid cysts). The viability
      criteria used were: ovoid form, invaginated scolices and intact calcareous
      corpuscles, the presence of vibrating movements, and the absence of "vital"
      staining. The cysts were grouped as univesicular cysts (UVC), multivesicular
      cysts (MVC) and abscessed cysts (LAHO). Fertility was defined as living
      protoscoleces in relation to the total number of protoscoleces. Descriptive
      statistics were for the calculation of the prevalence of fertility, analytical
      statistics for the comparison of groups, and a multivariate analysis for the
      examination of the association between cyst fertility and clinical variables.
      RESULTS: A total of 163 cysts with a median diameter of 15 cm were studied in
      this way. Of these lesions, 79 (48.5%) were UVC, 54 (33.1%) MVC, and 30 (18.4%)
      LAHO. On 99 occasions (60.7%), macroscopic communication was evident in the bile
      duct, and a prevalence of general fertility of 57.1% (94.4% for MVC, 53.2% for
      UVC, and 0% for LAHO, with a value of P<0.001). Association with location, type,
      and diameter of the cyst, and presence of biliary communications was verified by
      applying a bivariate analysis, and association between fertility and the
      variables of the type of the cyst and the existence of biliary communications was
      verified employing a multivariate analysis (P values of 0.004 and <0.001,
      respectively). CONCLUSIONS: The prevalence of fertility found was low. The main
      prevalence of fertility was observed in MVCs. Fertility is associated with the
      type of cyst and the presence of biliary communications.

PMID- 16425084
TI  - Mario Donati and the vertical mattress suture of the skin.
AB  - Mario Donati (1879-1946) was one of the foremost European surgeons of the early
      20th century. During an impressive carrier as surgeon, teacher, and innovator he
      authored more than 200 scientific works. Already as a young teacher he won the
      admiration of his colleagues: "His lectures were models of clarity and
      conviction, his originality and brilliance as a surgeon have well earned [him] a
      place among the most famous of the clinical masters of surgery of all eras"
      (Mario Donati. J. Int. Coll. Surg. 1946;9:739). The present review offers a brief
      biographical sketch of Donati's life and career, presents an eyewitness account
      of the origin of the Donati stitch, and discusses a possible precursor of this
      suture technique in the Middle Ages. On the occasion of the 60th anniversary of
      the end of World War II, the authors would like to pay a special homage to Mario
      Donati, who due to his Jewish ancestry was removed from his office as Professor
      of Surgery at the University of Milan in 1938 and died shortly after his return
      from exile in Switzerland.

PMID- 16425085
TI  - Clinical significance of focal adhesion kinase in resectable pancreatic cancer.
AB  - Focal adhesion kinase (FAK) is a non-receptor, cytoplasmic protein tyrosine
      kinase that is involved in the regulation of cellular signaling, migration,
      apoptosis, and cell cycle progression. Previous reports have shown that FAK is
      expressed in various kinds of cancer tissues and cancer cell lines; however, no
      information is available about human pancreatic carcinoma specimens. Tissue such
      specimens were obtained from 50 patients who underwent pancreatic resection for
      pancreatic invasive ductal carcinoma at our institute from 1996 to 2002.
      Immunohistochemical analysis of FAK was performed in the resected specimens.
      Focal adhesion kinase expression in seven human pancreatic cancer cell lines was
      analyzed by reverse transcription polymerase chain reaction (PCR) analysis and
      Western blot analysis. Focal adhesion kinase expression was detected in 24 of 50
      cases (48%). There was a statistically significant correlation between FAK
      expression and tumor size (P=0.004), although FAK expression did not
      significantly correlate with other factors such as tumor histological grade,
      lymph node metastasis, distant metastasis, histological stage, and overall
      survival. Reverse transcription PCR analysis and Western blot analysis showed
      that FAK was expressed in all seven pancreatic cancer cell lines. Focal adhesion
      kinase expression was not directly related to clinicopathological factors except
      tumor size in pancreatic carcinoma. Focal adhesion kinase expression may not be a
      prognostic marker for pancreatic cancer patients.

PMID- 16425086
TI  - Typhoid colonic perforation in childhood: a ten-year experience.
AB  - BACKGROUND: Intestinal perforation resulting from a complication of typhoid fever
      has always been of concern because of its high morbidity and mortality rates.
      Most perforations occur in the terminal ileum. METHODS: Between May 1995 and June
      2005, 24 children with typhoid colonic perforations receiving operations were
      retrospectively reviewed. The patients were 5 months to 86 months of age (mean:
      25.1+/-17.5 months). Surgical management consisted of primary closure of the
      perforation with ileostomy (70.8%), wedge resection and simple closure (20.8%),
      and partial colectomy with colostomy (4.2%). For the 11 patients with solitary
      cecal perforation, 6 received simple closure with ileostomy (group I), and wedge
      resection and simple closure was performed in the remaining 5 patients (group C).
      After operation, total parenteral nutrition (TPN) was instituted in each patient.
      RESULTS: Solitary cecal perforation is the most common type (45.8%). The length
      of hospital stay (LOS) varied from 12 days to 73 days, and the mean duration was
      24.5+/-14.7 days. The LOS showed no significant difference with regard to the
      location and the number of perforations. No mortality was noted in the entire
      series, but 19 patients had one or more complications, which may have prolonged
      the LOS; anemia and wound infections were the two most common problems. Group C
      had the shorter LOS (16.4+/-3.4 days, versus 40.2+/-22.6 days for group I) and
      fewer complications (0.6+/-0.5, versus 3.25+/-1.7 for group I). Any readmission
      for secondary operation to restore intestinal continuity in group C was therefore
      avoided. CONCLUSIONS: To understand thoroughly the clinical course of typhoid
      fever is important. The typically high rate of complications after intestinal
      perforation secondary to typhoid fever may be reduced if operation is undertaken
      earlier. Solitary cecal perforation can be managed safely with wedge resection
      and simple closure without bowel exterioration. Routine usage of TPN may reduce
      the mortality associated with complications resulting from typhoid perforations.

PMID- 16425087
TI  - Tuberculosis of the thyroid gland: review of the literature.
AB  - OBJECTIVE: Thyroid tuberculosis (TTB) is a very rare condition, even in countries
      with a high prevalence of tuberculosis. The aim of this article is to review and
      retrieve data about thyroid tuberculosis from the English-language literature in
      order to gain a better understanding of the clinical characteristics of TTB.
      STUDY DESIGN: We performed Medline, PubMed, and library searches using the key
      words "thyroid tuberculosis," "throid disease," "tuberculosis and thyroid."
      Reference lists of the articles obtained and previous reviews were also examined.
      RESULTS: We retrieved 76 cases matching our selection criteria from the search.
      Review of the cases with TTB revealed a slight female preponderance. The patients
      reported in the literature ranged in age from 9 to 83 years, with a median age of
      40+/-16 years for men and 44+/-17 years for women. In the articles surveyed, TTB
      presented with a broad spectrum of manifestations, ranging from an isolated
      nodule to thyrotoxicosis. It seems that diagnosis of thyroid tuberculosis has
      recently been increasing, perhaps because of the growing incidence of
      tuberculosis and the diagnostic use of fine-needle aspiration cytology in the
      diagnosis. Although, in the past, the diagnosis was generally made by the
      examination of the specimens, at present, fine-needle aspiration cytology seems
      to be a useful method in diagnosis tuberculous thyroiditis. The role of surgery
      is limited after the diagnosis. The choice of treatment should be medical
      antituberculous therapy. CONCLUSIONS: Preoperative diagnosis of thyroid
      tuberculosis is important because of the availability of medical treatment and
      the limited role of surgery. This condition should be kept in mind in evaluating
      patients with a thyroid nodule, in communities where the prevalence of
      tuberculosis is high.

PMID- 16425088
TI  - Loudness adaptation in acoustic and electric hearing.
AB  - The present study is aimed to evaluate and compare loudness adaptation between
      normal hearing and cochlear-implant subjects. Loudness adaptation for 367-s pure
      tones was measured in five normal-hearing subjects at three frequencies (125,
      1,000, and 8,000 Hz) and three levels (30, 60, and 90 dB SPL). In addition,
      loudness adaptation for 367-s pulse trains was measured in five Clarion cochlear
      implant subjects at three stimulation rates (100, 991, and 4,296 Hz), three
      levels (10, 50, and 90% of the electric dynamic range), three stimulation
      positions (apical, middle and basal), and two stimulation modes (monopolar and
      bipolar). The method of successive magnitude estimation was used to quantify
      loudness adaptation. Similar to the previous results, we found that loudness
      adaptation in normal-hearing subjects increases with decreasing level and
      increasing frequency. However, we also found a small but significant loudness
      enhancement at 90 dB SPL in acoustic hearing. Despite large individual
      variability, we found that loudness adaptation in cochlear-implant subjects
      increases with decreasing levels, but is not significantly affected by the rate,
      place and mode of stimulation. A phenomenological model was proposed to predict
      loudness adaptation as a function of stimulus frequency and level in acoustic
      hearing. The present results were not fully compatible with either the restricted
      excitation hypothesis or the neural adaptation hypothesis. Loudness adaptation
      may have a central component that is dependent on the peripheral excitation
      pattern.

PMID- 16425090
TI  - Comparative epidemiology of breast cancer among men and women in the US, 1996 to
      2000.
AB  - OBJECTIVE: Few investigations of breast cancer among men have been conducted
      because of the relative rarity of this malignancy. The objective of this analysis
      was to compare the demographic, pathological, and clinical features of breast
      cancer among men and women. METHODS: Breast cancer among 6379 men and 744,275
      women was identified through 34 US population-based registries in the US during
      the period 1996 to 2000. These registries were estimated to represent 69% of the
      US population. Age-adjusted incidence rates (AAIR) were calculated per million
      population using counts derived from the 2000 US census. RESULTS: The AAIR of
      breast cancer among men (16.6) was substantially lower than the incidence among
      women (1557.7). Rates of breast cancer among black men were higher than among
      white and Asian-Pacific Island men, in contrast to women among whom rates in
      whites exceeded those among other ethnic groups. Similar to women, breast cancer
      rates among non-Hispanic men were 50% greater than among Hispanic men. Ductal
      cancer was the most common histologic type diagnosed in both sexes. The incidence
      of lobular cancer was rare in men, but Paget's disease and papillary carcinoma
      occurred with lower relative frequency in women than in men. Lobular breast
      cancers were less common among black men and women than among other ethnic
      groups. In situ breast cancer was diagnosed in 10.8% of men and 16.2% of women.
      Localized breast cancer was the most common stage at diagnosis in both sexes and
      all ethnic groups, although women were more likely than men to be diagnosed at a
      localized stage. Cancer was 10% more likely to be diagnosed in the left breast
      than the right breast among men compared to 4% in women. CONCLUSIONS: In spite of
      the rare incidence of breast cancer in men, the descriptive epidemiology of this
      malignancy is surprisingly similar to that in women. An explanation for the
      greater relative incidence of breast cancer in black men is a research challenge.

PMID- 16425091
TI  - Dietary risk factors for ovarian cancer: the Adventist Health Study (United
      States).
AB  - Few prospective studies have reported dietary risk factors for ovarian cancer. A
      total of 71 histologically confirmed epithelial ovarian cancers occurred among
      13,281 non-Hispanic white California Seventh-day Adventist women during follow
      up. Participants were part of the Adventist Health Study (AHS) and had no history
      of cancer or hysterectomy at baseline in 1976 when they completed a detailed
      lifestyle questionnaire including a dietary assessment. The association of
      dietary variables with either all ovarian cancer cases or postmenopausal cases
      was tested using proportional hazards regression with adjustment for age and
      other covariates. The strongest hazardous risk factor associations among the food
      variables were found for meat intake with a risk ratio (RR) of 2.42 for intake >
      or = 1 time/week versus no meat (p for trend = 0.006), and cheese intake with a
      RR of 2.02 for intake of > 2 time/week versus < 1 per week (p for trend = 0.10),
      both of these being in postmenopausal cases. We found significantly reduced risk
      of all ovarian cancer with higher tomato consumption (RR = 0.32) comparing
      intakes > or = five times/week versus never to < 1 time/week (p for trend =
      0.002), and also with higher fruit consumption (p < 0.01). A weak protective
      association was found with low fat, but not whole milk. Little confounding was
      observed between these foods.

PMID- 16425092
TI  - Accessibility of web sites containing colorectal cancer information to adults
      with limited literacy (United States).
AB  - OBJECTIVE: The Internet could be a key channel for disseminating information
      about colorectal cancer (CRC) screening. Little research, however, has
      systematically examined factors other than writing style related to the reading
      difficulty of cancer information on the Internet. In the present study we
      assessed the reading difficulty of 19 CRC Web sites. METHODS: We assessed pages
      within selected sites containing information on CRC screening or prevention using
      the SMOG readability formula and Suitability Assessment of Materials instrument.
      RESULTS: The average SMOG reading grade level was 12.8. The SAM results indicated
      common problems with the sites, including (1) lack of review of key ideas; (2)
      insufficient use of illustrations for key messages; (3) crowded layout and long
      line lengths; (4) small type size and lack of cues to highlight key content; and
      (5) lack of interactive features. CONCLUSIONS: Many Web sites providing CRC
      information may be too difficult for the average American adult and much too
      difficult for adults with limited literacy. The unique features of the Internet
      that could support learning are not being utilized. The Internet could be a
      powerful tool for educating individuals about CRC, but the barrier of difficult
      content must be addressed along with access barriers.

PMID- 16425089
TI  - Prediction of anticancer drug potency from expression of genes involved in growth
      factor signaling.
AB  - PURPOSE: This study develops and evaluates a systematic approach to finding
      biomarker genes for predicting potency of anticancer drugs against tumor cells,
      focusing on gene families related to growth factor signaling. METHODS: Cytotoxic
      potencies of 119 drugs against 60 neoplastic cell lines (NCI-60) were correlated
      with expression of 343 genes, including 90 growth factors and receptors, 63
      metalloproteinases, and 92 ras-like GTPases as downstream signaling factors.
      Progressively more stringent criteria and predictive models aim at identifying
      the smallest subset of genes predictive of cytotoxic potency. RESULTS: Comparing
      gene expression with drug potency across the NCI-60 yielded genes with negative
      and positive correlations (p < 0.001), indicative of a role in chemoresistance
      and chemosensitivity, respectively. Of 17 genes with multiple negative
      correlations, 8 are known chemoresistance factors, validating the approach.
      Negatively correlated genes clustered into two main groups with distinct
      expression profiles and drug correlations, represented by EGFR and ERBB2 (Her
      2/Neu). Accordingly, no synergism was observed between EGFR and ERBB2 inhibitors.
      However, combinations with classical anticacer drugs were not correlated with
      EGFR and ERBB2 expression in four cell lines tested, suggesting complex
      interactions in combination treatments. Finally, a subset of only 13 genes was
      found to be sufficient for near optimal prediction of drug potency against the
      NCI-60. CONCLUSIONS: Our approach using a small subset of genes reveals known and
      potential biomarkers in cancer chemotherapy, providing a strategy for genome-wide
      analysis.

PMID- 16425093
TI  - Population-based mammography screening and breast cancer incidence in New South
      Wales, Australia.
AB  - OBJECTIVE: To analyse breast cancer incidence trends in New South Wales (NSW),
      Australia, in relation to population-based mammography screening targeting women
      aged 50 to 69 years. METHODS: Trends in age-specific incidence of invasive breast
      cancers in NSW women aged > or = 40 years were examined in relation to
      mammography screening rates and screening cancer detection rates. RESULTS:
      Incidence of invasive breast cancer in NSW women increased in all age-groups over
      1972 to 2002. The incidence trend for women aged 50 to 69 years showed that the
      steepest rise was associated with increased participation in population-based
      mammography screening, which was implemented from 1988 and achieved state-wide
      coverage in 1995. The elevated incidence of invasive cancer significantly
      exceeded pre-screening levels, and persisted after rates of initial screens
      declined. This elevated incidence was sustained by the contribution of cancers
      diagnosed through subsequent screening, and resulted from increased cancer
      detection rates in subsequent screens. CONCLUSIONS: The recent increase in
      invasive breast cancer incidence in NSW is associated with mammography screening,
      and occurred mostly in the target age-group women. Persistence of higher
      incidence after 1994 was not explicable by inflation of cancer incidence due to
      detection of prevalent screen cases, but was associated with a trend of increased
      cancer detection rates in subsequent screening rounds, probably consequent to
      quality improvements in mammography screening diagnosis.

PMID- 16425094
TI  - Do centralised skin screening clinics increase participation in melanoma
      screening (Australia)?
AB  - OBJECTIVE: To compare during the first 12 months of a 3-year randomised community
      based trial of population screening for melanoma three methods of screening
      delivery: skin screening within day-to-day primary care (Group A); screening in
      dedicated skin screening clinics either organised privately by local physicians
      (Group B); or organised centrally with participants referred back to their
      physicians for definitive diagnosis and management (Group C). METHODS: The trial
      involved 18 regional communities in Queensland, Australia. Of the nine
      communities randomised to the intervention group, three communities were
      allocated to each of the Groups A, B or C. All intervention communities received
      a community education programme and an education and support programme for
      primary care physicians. The self-reported prevalence of clinical skin
      examination was assessed by surveying 3,110 residents (66.9% participation rate)
      aged > or = 30 years by telephone at baseline, and 14,060 residents (70.9%
      participation rate) by self-administered mailed questionnaire at 12-month follow
      up. RESULTS: At baseline the prevalence of skin screening did not differ between
      intervention and control communities. At 12-month follow-up, participants within
      intervention communities reported skin screening significantly more frequently
      (20.9% versus 10.9%; p < 0.001). Within intervention communities, the prevalence
      of clinical skin examinations in Group A was similar to that of control
      communities (12.6% and 10.9%; p = 0.33). Communities in Group B (16.5%; p =
      0.001) and Group C (27.1%; p < 0.001) reported significantly higher prevalence of
      clinical examinations than the control group. CONCLUSIONS: The provision of
      centrally organised skin screening clinics significantly increases skin screening
      rates and may have relevance for future melanoma control programmes.

PMID- 16425095
TI  - Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the
      cancer prostate Sweden study (Sweden).
AB  - OBJECTIVE: Based on evidence that phytoestrogens may protect against prostate
      cancer, we evaluated the associations between serum enterolactone concentration
      or dietary phytoestrogen intake and risk of prostate cancer. METHODS: In our
      Swedish population-based case-control study, questionnaire-data were available
      for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone
      levels in a sub-group of 209 cases and 214 controls. Unconditional logistic
      regression was performed to estimate multivariate odds ratios (ORs) and 95%
      confidence intervals (CIs) for associations with risk of prostate cancer.
      RESULTS: High intake of food items rich in phytoestrogens was associated with a
      decreased risk of prostate cancer. The OR comparing the highest to the lowest
      quartile of intake was 0.74 (95% CI: 0.57-0.95; p-value for trend: 0.01). In
      contrast, we found no association between dietary intake of total or individual
      lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels
      of enterolactone were associated with a decreased risk of prostate cancer. The
      ORs comparing increasing quartiles of serum enterolactone concentration to the
      lowest quartile were, respectively, 0.28 (95% CI: 0.15-0.55), 0.63 (95% CI: 0.35
      1.14) and 0.74 (95% CI: 0.41-1.32). CONCLUSIONS: Our results support the
      hypothesis that certain foods high in phytoestrogens are associated with a lower
      risk of prostate cancer.

PMID- 16425096
TI  - Postal workers' occupational and leisure-time sun safety behaviors (United
      States).
AB  - OBJECTIVES: United States Postal Service letter carriers are exposed to long
      bouts of UVR and thus are vulnerable to skin cancer. While previous studies have
      shown that occupational sun protection is often deficient, few studies have
      examined outdoor workers' behavior during leisure time. METHODS: Subjects (n =
      2,660) self-reported widebrim hat and sunscreen use over the past five workdays
      and past two non-working days using Likert-type scales. Generalized linear mixed
      models and generalized estimating equations were used to compare hat and
      sunscreen rates and predictors during occupational and leisure time. RESULTS: On
      average, carriers spent 3.9 h outside during workdays and 3.3 h during non
      working days. Sunscreen and widebrim hat use during the workday is low and rates
      of use are significantly lower during non-working days. CONCLUSIONS: Sun safety
      interventions for carriers should encourage sun protection at all times when
      outdoors.

PMID- 16425097
TI  - Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its
      Interaction with the Androgen Receptor (United States).
AB  - OBJECTIVE: To determine whether directly observed prostate-specific antigen (PSA)
      promoter diploid haplotype, either alone or in conjunction with androgen receptor
      (AR) genotype, is associated with prostate cancer risk. METHODS: We conducted a
      case-control study nested within the US population-based Cardiovascular Health
      Study cohort. Incident prostate cancers were identified by linkage to cancer
      registry records for the years 1989-2000. We genotyped 193 cases and 391 controls
      for the PSA -252 G/A and -158 G/A SNPs and the AR CAG microsatellite, and
      developed methods to directly determine proximal PSA promoter haplotypes. Exact
      logistic regression was used to estimate odds ratios and significance levels.
      RESULTS: No significant associations were observed between PSA diplotype and
      prostate cancer overall. Short (< 20) AR CAG repeat lengths were associated with
      modest increases in the risk of prostate cancer (OR, 1.46; 95% CI, 0.97-2.19; p =
      0.071) that were significant for advanced disease (OR, 1.82; 95% CI, 1.02-3.26; p
      = 0.044). Men who possessed two copies of the PSA*2 (-252G/-158G) haplotype and
      short AR CAG repeat lengths had a 4-fold (95% CI, 1.05-20.75; exact p = 0.040)
      increased risk of prostate cancer, and a 7-fold (95% CI, 1.25-39.78; exact p =
      0.026) increased risk of advanced disease. CONCLUSIONS: We found evidence that
      the PSA*2*2 diplotype in combination with short AR CAG alleles increases a man's
      risk of developing prostate cancer. These findings support an etiologic role in
      prostate cancer of genetic interactions between polymorphisms that increase AR
      transactivation strength and those that alter the regulatory regions of target
      genes such as PSA that are responsive to androgen stimulation.

PMID- 16425098
TI  - Diet after diagnosis and the risk of prostate cancer progression, recurrence, and
      death (United States).
AB  - OBJECTIVES: We examined post-diagnostic diet and risk of cancer progression in a
      cohort of men with prostate cancer from the Health Professionals Follow-up Study.
      METHODS: We observed 392 progression outcomes among 1,202 men diagnosed with
      incident localized/regional prostate cancer between 1986 and 1996. Men completed
      prospective dietary surveys before and after diagnosis and were followed through
      2000. We examined post-diagnostic consumption of red meat, grains, vegetables,
      fruits, milk, tomatoes, tomato sauce, and fish as predictors of progression using
      Cox proportional hazard regression models adjusted for total energy, age,
      clinical factors, and pre-diagnostic diet. RESULTS: Men in the highest versus
      lowest quartile of post-diagnostic fish consumption had a multivariate hazard
      ratio (HR) of progression of 0.73 (95% CI 0.52-1.02); the comparable HR for
      tomato sauce was 0.56 (95% CI 0.38-0.82). We observed inverse linear
      relationships for fish and tomato sauce and risk of progression (HR = 0.83, p
      value = 0.006 and HR = 0.80, p-value = 0.04 for a two serving/week increase of
      fish and tomato sauce, respectively). Milk and fresh tomato consumption were
      associated with small elevations in risk. CONCLUSIONS: These data suggest that
      diet after diagnosis may influence the clinical course of prostate cancer, and
      fish and tomato sauce may offer some protection against disease progression.

PMID- 16425099
TI  - Incidence and characteristics of childhood Hodgkin's lymphoma in Greece: a
      nationwide study (Greece).
AB  - OBJECTIVES: To estimate the incidence and epidemiological profile of childhood (0
      14 years) Hodgkin's lymphoma in Greece derived by the network of childhood
      Hematology-Oncology departments on the basis of all 95 newly diagnosed cases
      during a seven-year period. METHODS: Seventy-one of these cases were individually
      age and gender matched to an equal number of controls. RESULTS: The incidence of
      childhood Hodgkin Lymphoma reached a relatively high figure of 7.8 per million
      children-years, with an age distribution (2.2 for children 0-4; 6.3 for those 5-9
      and 13.9 for those 10-14-years-old) and male to female ratio (1.7:1) similar to
      that reported from other cancer registries. Childhood Hodgkin's lymphoma was more
      common among children living in less crowded quarters (odds ratio (OR): 6.5 and
      95% confidence intervals (95% CI): 1.4-30.7), among those who have changed
      residence 60 to 18 months before the onset of the index disease (OR: 4.4, and 95%
      CI = 1.4-14.0), among those whose families owned a cat (OR: 5.5, 95% CI = 1.2
      25.6) but not among those whose families owned a dog and marginally more common,
      among those with a history of infectious mononucleosis (OR: 5.0, 95% CI = 0.6
      42.8). CONCLUSIONS: Our results point to infectious agent(s) as playing an
      etiological role but do not allow discrimination among the delayed establishment
      of the herd immunity hypothesis, the population mixing hypothesis or that
      invoking transmission of the agent(s) from the non-human reservoir.

PMID- 16425101
TI  - Causal effects of smokeless tobacco on mortality in CPS-I and CPS-II?

PMID- 16425100
TI  - Race/ethnicity and changing US socioeconomic gradients in breast cancer
      incidence: California and Massachusetts, 1978-2002 (United States).
AB  - OBJECTIVE: We tested the hypothesis that the US socioeconomic gradient in breast
      cancer incidence is declining, with the decline most pronounced among
      racial/ethnic groups with the highest incidence rates. METHODS: We geocoded the
      invasive incident breast cancer cases for three US population-based cancer
      registries covering: Los Angeles County, CA (1978-1982, 1988-1992, 1998-2002; n =
      68,762 cases), the San Francisco Bay Area, CA (1978-1982, 1988-1992, 1998-2002; n
      = 37,210 cases) and Massachusetts (1988-1992, 1998-2002; n = 48,111 cases),
      linked the records to census tract area-based socioeconomic measures, and, for
      each socioeconomic stratum, computed average annual breast cancer incidence rates
      for the 5-year period straddling the 1980, 1990, and 2000 census, overall and by
      race/ethnicity and gender. RESULTS: Our findings indicate that the socioeconomic
      gradient in breast cancer incidence is: (a) relatively small (at most 1.2) and
      stable among US white non-Hispanic and black women; (b) sharper and generally
      increasing among Hispanic and Asian and Pacific Islander American women; and (c)
      cannot be meaningfully analyzed without considering effect modification by
      race/ethnicity and immigration. CONCLUSION: Our results indicate that secular
      changes in US socioeconomic gradients in breast cancer incidence exist and vary
      by race/ethnicity.

PMID- 16425102
TI  - Clinical characteristics and service utilization patterns of clients with
      schizophrenia-spectrum disorders in public residential detoxification settings.
AB  - Little is known about the treatment needs of clients found in residential
      detoxification programs who have comorbid schizophrenia-spectrum and substance
      use disorders. This study (N = 166) compares the service use patterns of comorbid
      detoxification clients with schizophrenia-spectrum disorders (CDT-S) to two other
      client groups: (1) comorbid detoxification clients with other mental health
      disorders (CDT-O), and (2) comorbid clients in residential mental health
      facilities with schizophrenia-spectrum disorders (CMH-S). Results show that CDT-S
      clients were much less likely to receive subsequent mental health treatment than
      CMH-S clients. Findings indicate that detoxification programs may be important
      settings in which to identify clients with schizophrenia who have unmet mental
      health treatment needs.

PMID- 16425103
TI  - Behavioral changes and acute toxicity to the freshwater shrimp Atyaephyra
      desmaresti Millet (Decapoda: Natantia) from exposure to acid mine drainage.
AB  - Short-term 48 h laboratory bioassays with water from an acid mine drainage (AMD:
      pH 3.3, 4.4, 5.0, 5.5, 6.4, control) and water from an arsenic containing
      reservoir were performed with the freshwater shrimp Atyaephyra desmaresti Millet,
      validated in situ and compared to acidified control water (ACID). Behaviour,
      mortality and time to death were monitored with the Multispecies Freshwater
      Biomonitor (MFB). The shrimps had equal 24 h-LC50s at pH 4 in AMD and ACID.
      However, after 48 h AMD proved more toxic (48 h-LC50 at pH 5.2) than ACID (48 h
      LC50 at pH 4.5). Stress behaviour in AMD consisted at pH < or = 6.4 of a pH
      dependent decrease in activity, with disappearance of circadian rhythmicity, and
      at pH 4.4 a clear increase of ventilation. At pH 5.5 bioaccumulation of metals
      was higher and locomotion lower than at pH 5.0. In ACID, only at pH < or = 4.4
      locomotion became abated and arythmic. Locomotion in the field was equal or
      higher compared to the laboratory, whereas the ventilation was higher in the
      laboratory. A. desmaresti is a valuable species to be used in short term
      behavioural bioassays of AMD in Europe.

PMID- 16425104
TI  - Effects of self-fertilization, environmental stress and exposure to xenobiotics
      on fitness-related traits of the freshwater snail Lymnaea stagnalis.
AB  - Genetic and ecological factors may interact in their effects on fitness. Such
      interactions are thus to be expected between inbreeding and exposure of a
      population to a toxicant. The magnitude of inbreeding depression is thought to
      increase in stressful environments. To test this hypothesis, we investigated the
      combined effects of environmental conditions and inbreeding on fitness in the
      self-fertile snail Lymnaea stagnalis, using a stress gradient (0-2) applied to a
      100 isolated and paired lineages: laboratory control (0), outdoor microcosm
      control (1) and pesticide exposure under outdoor microcosm conditions (2).
      Outdoor stress conditions were maintained for 28 days prior to measurements of
      fitness traits (fecundity, hatching success, and size at hatching) under
      laboratory conditions, so that delayed environmental effects could be estimated.
      Under laboratory control conditions, we found significant initial family level
      heterogeneity for most measured traits, including physiological performances as
      assessed through energetic biomarkers. Whatever the environmental conditions,
      inbreeding depression was very low for progeny performances. Negative values of
      self-fertilization depression (SFD) were obtained. Unexpectedly, SFD showed a
      negative relationship with the assumed stress intensity, reflecting a higher
      sensitivity under pairing than under selfing, mostly due to parental fecundity.
      This suggests that stressful conditions may favour selfing. Stress intensity
      increased the distribution limits of both depression indices, suggesting that
      changes in fitness are less predictable in a population under stress.
      Implications of such findings for environmental risk assessment of pesticides are
      discussed.

PMID- 16425106
TI  - Homeopathy and mainstream medicine: a dialogue of the deaf?
AB  - Various definitions of complementary and alternative medicine have been proposed.
      Homeopathy is unique among CAM therapies in originating in European Enlightenment
      thought. It is controversial and scientifically implausible yet popular,
      widespread and durable. The result has been a longstanding 'dialogue of the
      deaf', with little progress or genuine discussion. Clinical collaboration and
      serious and scientific discourse concerning homeopathy is possible and should be
      pursued. The alternative is not that homeopathy disappears but that it is
      absorbed into a dis-affected medical counter-culture with adverse consequences,
      particularly for patients. The Royal London Homoeopathic Hospital is developing
      clinical integration and scientific collaboration with a major academic medical
      centre in London.

PMID- 16425107
TI  - To which extent should potency choice in homeopathy be "regulated": has European
      legislation gone too far?
AB  - Despite ongoing controversy, homeopathy has become increasingly accepted as a
      "medical reality" by patients and doctors alike. This process has been
      accompanied by an increased quality of manufacturing, education, research, and
      regulation of homeopathy. This paper argues that European regulation may now have
      gone too far by indiscriminately prescribing that homeopathic medicines should be
      used in a potency of D4 and higher. Low potencies and tinctures are an important
      and integral part of the homeopathic heritage. The regulatory environment
      therefore appears to be hampering one of its own principal aims: the availability
      of safe and high-quality homeopathic products that practitioners, patients and
      consumers want and need.

PMID- 16425109
TI  - Homeopathy in emergency medicine.
AB  - BACKGROUND: Use of homeopathy is not frequently reported in critically ill
      patients. We describe our experience treating such patients homeopathically in
      the emergency room, on the wards, and in the intensive care unit of conventional
      hospitals in Austria and Israel. METHODS: We describe a case series of patients
      treated in the ER for multiple casualty incidents, two case reports of remarkable
      cures in the ICU, and two RCTs demonstrating the efficacy of homeopathy in septic
      and intubated patients. RESULTS: A case series documents favorable results in
      homeopathic treatment of patients in the ER and wards after multiple casualty
      incidents. Two case reports narration e remarkable homeopathic cures to
      imminently terminal illnesses. Finally, homeopathy was demonstrated effective as
      compared with placebo in improving long-term survival in severely ill septic
      patients and in hastening extubation ICU patients. CONCLUSIONS: Our report
      suggests that homeopathy may be applicable even for critically ill patients. We
      discuss the obstacles encountered, including a dearth of tools for successful
      homeopathic prescription in these situations, suspicion and lack of cooperation
      by patients and conventional colleagues, and the highly suppressive nature of
      concomitant conventional therapies. We suggest the development of algorithms and
      other tools to aid rapid homeopathic prescription in critical care patients and
      discuss the importance of familiarizing physicians and medical students with
      homeopathy in order to facilitate communication and cooperation between these
      complementary branches of medicine.

PMID- 16425108
TI  - [On the effectiveness of the homeopathic remedy Arnica montana].
AB  - BACKGROUND: Arnica montana is a homeopathic remedy often prescribed after
      traumata and injuries. OBJECTIVES: To assess whether Arnica is effective beyond
      placebo and to identify factors which support or contradict this effectiveness.
      METHODS: All prospective, controlled trials on the effectiveness of homeopathic
      Arnica were included. Overall effectiveness was assessed by meta-analysis and
      meta-regression techniques. RESULTS: 68 comparisons from 49 clinical trials show
      a significant effectiveness of Arnica in traumatic injuries in random effects
      meta-analysis (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.24-0.55),
      but not in meta-regression models (OR, 0.37; CI, 0.11-1.24). We found no evidence
      for publication bias. Studies from Medline-listed journals and high-quality
      studies are less likely to report positive results (p = 0.0006 and p = 0.0167).
      CONCLUSIONS: The hypothesis that homeopathic Arnica is effective could neither be
      proved nor rejected. All trials were highly heterogeneous, meta-regression does
      not help to explain this heterogeneity substantially.

PMID- 16425110
TI  - Practitioner empathy, patient enablement and health outcomes of patients
      attending the Glasgow Homoeopathic Hospital: a retrospective and prospective
      comparison.
AB  - Practitioner empathy and patient enablement at a "contact" consultation were
      retrospectively associated with changes in main complaint and well-being, in a
      cross-sectional study of out-patients attending the Glasgow Homoeopathic
      Hospital. Patient expectation, relational continuity, and duration of attendance
      at the hospital were also correlated with perceived change in health outcome in
      univariate analysis. However, multi-regression analysis suggested three major
      independent variables associated with health outcome -- empathy, enablement, and
      duration of attendance. Health outcomes were then measured in the same cohort 12
      months after "contact" consultation. Both univariate and multivariate analysis
      indicated that the only significant predictive factor in health change over the
      12-month period was patient enablement score at contact consultation. This study
      demonstrates the importance of prospective studies in assessing potentially
      causal relationships between consultation quality and health outcomes and
      suggests a key role for patient enablement.

PMID- 16425111
TI  - [Is the pharmaceutical industry really as bad as its reputation?].
AB  - The pharmaceutical industry has a bad image. Recently it has often also been
      criticised in internationally well-known medical journals. An exact examination
      in the context of the peculiarities of the pharmaceutical products' market has
      shown that there are at present five areas where ethical problems in the
      pharmaceutical industry exist: poor information flow, the relationship between
      the pharmaceutical industry and public health authorities, security standards and
      the scientific quality of research, provisioning, and priorities in research. It
      is difficult for the pharmaceutical industry to cope with conflicts of interest
      and their implications in these areas. There are surely individual ethical
      deficiencies and shortcomings but this is no reason for the whole branch to be
      castigated. In comparison to other branches, the pharmaceutical industry is much
      better than its image. People have to consume pharmaceutical products even though
      they do not like doing so, and therefore cannot be expected to champion the cause
      of the branch. It needs to adopt another strategy in order to improve its image.

PMID- 16425115
TI  - Recipient vessels for microsurgical flaps to the groin and pelvis: a review.
AB  - Reconstruction of large defects of the pelvis and groin sometimes requires
      microsurgical flaps when the otherwise rich supply of local options fails to be
      sufficient in difficult and complicated cases. Recipient vessels for
      microsurgical flaps to the groin and pelvis are important elements in planning
      such procedures. Seven groups have reported pelvis and groin microsurgical flap
      cases, and their recipient vessels have included the superior and inferior
      gluteal vessels, the femoral vessels, the deep perforators of the femoral system,
      the inferior epigastric vessels, intra-abdominal vessels, and interpositional
      vein grafts to distant recipient vessels. This review summarizes their experience
      and describes the recipient vessel options in the pelvic and groin region.

PMID- 16425116
TI  - Salvage of amputated upper extremities with temporary ectopic implantation
      followed by replantation at a second stage.
AB  - Salvage of the complex amputation of extremities, such as combined with
      devastating segmental injuries, extensive soft tissue defect, and multiple
      important organ injuries, continues to be a challenge for plastic surgeons.
      Temporary ectopic implantation of the amputated part to a healthy recipient site
      allows the patient to recover from critical combined injuries, radical
      debridements, and soft tissue repair. In this article, the authors report two
      cases of temporary ectopic implantation of complexly amputated forearms, followed
      by successful replantation to their anatomic positions at a second stage. The
      contralateral upper extremity is an acceptable recipient site for temporary
      ectopic implantation. In secondary replantation, a cross-arm flap can be designed
      to carry the vascular pedicle from the ectopic implantation recipient to improve
      blood supply to the replanted part when the second blood supply is established.
      The authors validated that temporary ectopic implantation of amputated parts
      provides an alternative procedure for the salvage of amputated extremities under
      special circumstances.

PMID- 16425117
TI  - Osteonecrosis of the femoral head: comparison of clinical results for
      vascularized iliac and fibula bone grafting.
AB  - Thirty-three patients (39 hips) with avascular necrosis of the femoral head
      (ANFH), who received vascularized iliac pedicle bone grafting at the Orthopaedic
      Department of Linkou Medical Center, Chang-Gung Memorial Hospital, were followed
      for more than 4 years (Group 1). Twenty-two patients with ANFH, who received free
      vascularized fibula bone grafting (Group 2) were followed for more than 3 years.
      Six parameters were adopted to evaluate the outcomes in both groups. Study
      results for the parameters of postoperative functional score, patient-evaluated
      outcome, radiographic progression, and conversion to replacement arthroplasty
      were not significantly different. However, the mean operation time for Group 2
      was significantly longer than that for Group 1 (7 hr vs. 3.5 hr) and the mean
      complication rate for Group 1 was higher than that for Group 2 (8/39 vs. 1/22).
      Since both are palliative procedures with almost equal success rates, the easier
      procedure was chosen and complications carefully avoided.

PMID- 16425118
TI  - Devastating massive knee defect reconstruction using the cornucopian chimera flap
      from the subscapular axis: two case reports.
AB  - Two cases of successful reconstruction of massive defects around the knee with
      multiple-island combined flaps based on the subscapular axis are reported. Both
      defects resulted from aggressive debridement for acute osteomyelitis after open
      fixation of high-energy fractures around the knee. In Case 1, a four-island
      combined flap consisting of the scapular flap, the lattissimus dorsi muscle flap,
      the serratus anterior muscle flap, and the scapular osseous flap, based on the
      same subscapular axis, was used. Partial bone transport using the Ilizarov
      apparatus was added as reinforcement of arthrodesis. In Case 2, a five-island
      combined flap, consisting of the scapular, parascapular flap, the lattissimus
      dorsi muscle flap, the serratus anterior fascial flap, and the scapular osseous
      flap, was used. Consequent ankylosis of the knee joint afforded the patient
      painless full weight bearing without secondary arthrodesis. Multiple-island
      combined flaps based on the subscapular axis can provide three-dimensional
      reconstruction of destructive knee defects.

PMID- 16425120
TI  - Single-stage reconstruction of the flexor mechanism of the fingers with a free
      vascularized tendon flap: case report.
AB  - The reconstruction of the flexor tendon in zones I and II of a ring finger in a
      single stage, using a free vascularized tendon graft, is reported in a single
      clinical case. The flexor digitorum superficialis (FDS) tendon of the same finger
      was freely transferred based on a vascular branch off the ulnar vessels. The
      ulnar artery was reconstructed with an end-to-end anastomosis, and the free flap
      was connected to the superficial palmar arch. The functional result was
      satisfactory.

PMID- 16425119
TI  - Restoration of thumb abduction damaged by electrical burn using the free dorsalis
      pedis flap with the extensor hallucis brevis tendon.
AB  - The treatment of electrical burn injuries in the hand is difficult and
      challenging because the burn widely and deeply damages not only the skin and
      subcutaneous tissue, but also tendon, muscle, ligaments, and bone. Compound
      defects of the skin and abductor pollicis brevis tendon caused by an electrical
      injury were reconstructed using a free dorsalis pedis flap including the extensor
      hallucis brevis tendon. This composite flap is also applicable for reconstruction
      of thumb abduction, although its usefulness has been reported for reconstruction
      of defects of the dorsal skin of the hand including the extensor tendons.

PMID- 16425121
TI  - Free fasciocutaneous flaps in the treatment of chronic osteomyelitis of the
      tibia: a retrospective study.
AB  - The efficacy of free fasciocutaneous flaps for the treatment of chronic
      osteomyelitis of the tibia was evaluated in a retrospective study. A series of 14
      patients is reported who underwent soft-tissue reconstruction using different
      free fasciocutaneous flaps after radical debridement. Radical debridement and
      microvascular reconstruction were performed in two operative steps. The mean
      duration of disease was 14 years (range: 6 months to 37 years). At a mean follow
      up of 31.4 (12 to 52) months, there was no evidence of recurrence of
      osteomyelitis. This retrospective study validates that fasciocutaneous flaps can
      be used for microsurgical soft-tissue reconstruction after radical debridement in
      the treatment of chronic osteomyelitis. The introduction of free fasciocutaneous
      flaps has challenged the dictum of the therapy of chronic osteomyelitis with
      muscle flaps.

PMID- 16425122
TI  - Cross-sectional internal diameters of radial, thoracodorsal, and dorsalis pedis
      arteries in children: relationship to subject sex, age, and body size.
AB  - The purpose of this study was to determine the average diameter of the radial,
      thoracodorsal, and dorsalis pedis arteries in a pediatric population and to
      evaluate the relationship of these measurements to the subject's age, sex,
      height, weight, and body mass index (BMI). The internal diameters of the radial,
      thoracodorsal, and dorsalis pedis arteries were non-invasively studied in 45
      normotensive, presumed normal children of various ages (4 to 14 years) with the
      use of a Doppler system. The average diameters of the radial, thoracodorsal, and
      dorsalis pedis arteries in females and males were as follows: radial artery 1.39
      (SD +/- 0.18) mm and 1.57 (SD +/- 0.18) mm; thoracodorsal artery 1.27 (SD +/-
      0.11) mm and 1.36 (SD +/- 0.2) mm; and dorsalis pedis artery 1.22 (SD +/- 0.08)
      mm and 1.34 (SD +/- 0.12) mm. These were correlated with the age, height, weight,
      and BMI. Gender had a strong influence on the diameter of these arteries. In a
      linear regression model, weight was found to be statistically the best
      independent variable for predicting radial and dorsalis pedis diameters, whereas
      age was the best predictor for the diameter of the thoracodorsal artery. The
      diameters of these three arteries in an age group of 4 to 14 years ranged between
      1 to 2 mm. The age and weight of the children predicted the diameters of the
      peripheral arteries.

PMID- 16425123
TI  - Robotics in plastic and reconstructive surgery: use of a telemanipulator slave
      robot to perform microvascular anastomoses.
AB  - Many methods for microvascular anastomoses exist, including use of magnifying
      loupes (x 2.5, x 3.5, x 4.5, x 6), but the operating microscope remains the gold
      standard. The authors present the da Vinci Surgical System (Intuitive Surgical,
      Sunnyvale, CA) as an alternative method for performing microvascular anastomoses.
      The da Vinci robot has fully articulating microinstruments with six degrees of
      freedom, the ability to filter tremor, the capability to perform telesurgery, and
      the advantage of 3-D visualization. It offers full and dynamic control over the
      operating camera, allowing variable positioning and the ability to scale down
      movements. Its drawbacks include initial high cost, lack of haptic feedback,
      decreased participation of the first assistant, and lack of widespread
      availability. In this feasibility study, multiple microanastomoses were performed
      in canine tarsal and superficial femoral vessels.

PMID- 16425124
TI  - Sarpogrelate hydrochloride, an antagonist of 5-hydroxytryptamine receptor,
      improves skin flap survival and suppresses thrombus formation in injured
      microvessels of rabbits.
AB  - The authors carried out two studies to examine the effects of the 5
      hydroxytryptamine receptor antagonist, sarpogrelate hydrochloride (SH), on flap
      necrosis. The first study measured survival rates and included histologic
      examination of random-pattern skin flaps in rabbits. The second study assessed
      the time to complete obstruction of blood flow with the artificial thrombus
      formation method, and the time for leukocytes to adhere to the endothelium of
      microvessels in a rabbit-ear chamber. The treatment groups were injected with SH.
      The survival rates of skin flaps in the SH-treated group were increased
      significantly. Histologic examination of vessels in the control group revealed
      that vessels in the deep dermis were obstructed completely by thrombi, whereas
      such vessels were not obstructed in the SH-treated group. Thrombus formation time
      and leukocyte adhesion time in the SH-treated group were prolonged and decreased,
      respectively. Thus, SH maintained flap circulation and promoted flap survival by
      preventing thrombus formation.

PMID- 16425125
TI  - Development of nevirapine resistance in infants is reduced by use of infant-only
      single-dose nevirapine plus zidovudine postexposure prophylaxis for the
      prevention of mother-to-child transmission of HIV-1.
AB  - We analyzed the development of nevirapine (NVP) resistance in human
      immunodeficiency virus type 1 (HIV-1)-infected Malawian infants who received
      regimens containing single-dose NVP (SD-NVP) for the prevention of mother-to
      child transmission (MTCT) of HIV-1. All infants received SD-NVP, and some
      randomly received zidovudine (ZDV) as well. Mothers did or did not receive SD-NVP
      on the basis of when they arrived at the hospital for delivery. In infants 6-8
      weeks of age, NVP resistance was less frequent when infants had received SD-NVP
      plus ZDV and mothers had not received SD-NVP than when infants had received SD
      NVP alone and mothers had received SD-NVP (4/15 [27%] vs. 20/23 [87%]; P < .001).
      The risk of MTCT of HIV-1 was comparable with these regimens. Infant-only
      prophylaxis also eliminates the development of NVP resistance in mothers.

PMID- 16425126
TI  - Low risk of nevirapine resistance mutations in the prevention of mother-to-child
      transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus,
      Abidjan, Cote d'Ivoire.
AB  - The frequency of resistance mutations was estimated in the cohort of Agence
      Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the
      combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single
      dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the
      prevention of mother-to-child transmission of human immunodeficiency virus type 1
      (HIV-1). The frequency with which resistance mutations were detected in mothers
      at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.03%-6.17%) for
      NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate analysis, 3TC
      resistance was associated with a longer duration of ZDV plus 3TC prepartum
      prophylaxis (P=.009). This regimen, which is feasible in resource-limited
      settings, prevents most peripartum HIV-1 transmission and minimizes the
      development of NVP resistance.

PMID- 16425127
TI  - Cytomegalovirus-specific immunity and protection against viremia and disease in
      HIV-infected patients in the era of highly active antiretroviral therapy.
AB  - To define the immune correlates of protection against cytomegalovirus (CMV) end
      organ disease, CMV-specific interferon (IFN)- gamma enzyme-linked immunospot
      (ELISPOT) and CD8(+) and CD4(+) intracellular IFN- gamma synthesis assays were
      performed for subjects with CD4(+) cell counts of < or =50 cells/ microL who were
      enrolled in a prospective observational study of CMV infection in the era of
      highly active antiretroviral therapy. Of 87 subjects, 46 developed viremia, 14
      developed end-organ disease, and 20 died. Positive ELISPOT assay results, but not
      positive results for CD4(+) or CD8(+) intracellular IFN- gamma synthesis, were
      associated with delayed development of viremia and CMV end-organ disease or
      death. CMV viremia did not appear to boost CMV-specific immunity. ELISPOT assays
      may be used to identify HIV-infected patients who might benefit from anti-CMV
      prophylactic interventions.

PMID- 16425128
TI  - Abnormal presence of semimature dendritic cells that induce regulatory T cells in
      HIV-infected subjects.
AB  - Dendritic cells (DCs), because they orchestrate the immune response to microbes,
      represent an ideal target for pathogens attempting to evade the immune system. We
      hypothesized that interactions between human immunodeficiency virus (HIV) and DCs
      lead to the development of a semimature state, in which DCs migrate to lymph
      nodes but induce tolerance in T cells, rather than immunity. We found that lymph
      nodes from untreated HIV-infected subjects contained an abundance of semimature
      DCs, the disappearance of which correlated with the initiation of highly active
      antiretroviral therapy (HAART). Such lymph nodes also contained an abundance of T
      cells that had a regulatory phenotype and that persisted after HAART. Lymph node
      DCs from untreated HIV-infected subjects cultured with normal allogeneic T cells
      induced these T cells to adopt the phenotype of regulatory T cells, an ability
      that was lost after HAART. We conclude that HIV infection correlates with the
      presence of semimature DCs that stimulate T cell tolerance rather than immunity.
      These regulatory T cells may contribute to the lack of effective HIV immune
      responses.

PMID- 16425129
TI  - Increased plasma interleukin-7 level correlates with decreased CD127 and
      Increased CD132 extracellular expression on T cell subsets in patients with HIV-1
      infection.
AB  - BACKGROUND: Interleukin (IL)-7 levels are increased in patients with human
      immunodeficiency virus type 1 (HIV-1)-associated lymphopenia; however, the
      effects of this on IL-7 receptor (IL-7R) expression, disease progression, and
      immune reconstitution remain unclear. METHODS: Plasma IL-7 levels were measured,
      by enzyme-linked immunoassay, in patients with primary, chronic, or long-term
      nonprogressive HIV-1 infection (PHI, CHI, and LTNP, respectively) before and
      after 40-48 weeks of antiretroviral therapy (ART). Cell-surface expression and
      intracellular expression of the IL-7R components CD127 and CD132 were measured by
      flow cytometry. The effects of IL-7 and cycloheximide on IL-7R expression by
      peripheral blood mononuclear cells were examined in vitro. RESULTS: Plasma IL-7
      levels were increased in both patients with PHI and those with CHI;
      administration of ART resulted in normalized plasma IL-7 levels in patients with
      PHI but not in those with CHI. Plasma IL-7 levels positively correlated with
      CD4(+) T cell immune reconstitution in patients with PHI. In vitro, exogenous IL
      7 rapidly down-regulated cell-surface CD127 expression, but not CD132 expression,
      whereas subsequent reexpression required active protein synthesis. HIV-1
      infection resulted in progressive decreases in the CD127(+)132(-) subset and
      increases in the CD127(-)132(+) subset of CD4(+) and CD8(+) T cells. Changes in
      CD4(+) T cell expression of IL-7R components were evident in patients with LTNP
      who lost viral control, and these changes preceded increases in plasma IL-7
      levels. CONCLUSIONS: Perturbations in the IL-7/IL-7R system were clearly
      associated with disease progression but did not reliably predict immune
      reconstitution.

PMID- 16425130
TI  - Safety and immunogenicity of Escherichia coli O157 O-specific polysaccharide
      conjugate vaccine in 2-5-year-old children.
AB  - BACKGROUND: Escherichia coli O157:H7 causes severe enteritis and hemolytic-uremic
      syndrome, mostly in young children and older adults. Similar to the case with
      Shigella, serum IgG against the O-specific polysaccharide of E. coli O157:H7 may
      confer immunity by lysing the inoculum in the intestine. A phase 1 trial in
      adults showed that a vaccine of E. coli O157:H7 O-specific polysaccharide
      conjugated to recombinant exotoxin A of Pseudomonas aeruginosa (O157-rEPA) was
      safe and immunogenic. METHODS: A phase 2 trial of the O157-rEPA vaccine was
      conducted in 49 children 2-5 years old who were divided randomly into groups
      receiving 1 or 2 doses of vaccine. Adverse reactions were monitored. Serum IgG
      lipopolysaccharide (LPS) antibodies were determined. RESULTS: No significant
      adverse reactions were observed. At 1 week after the first dose was administered,
      most children (81%) responded with a >4-fold increase in serum IgG LPS
      antibodies. At 6 weeks after the first dose was administered, all children
      responded with a >8-fold increase; a second dose did not elicit a booster
      response. At 26 weeks after the first dose was administered, the geometric mean
      titer of serum IgG LPS antibodies was ~20-fold higher than was the prevaccination
      titer. These serum samples had high titers of bactericidal activity that were
      correlated roughly with serum IgG LPS antibody titers (r = .78). CONCLUSIONS: The
      O157-rEPA vaccine was safe and immunogenic in young children. A phase 3 trial of
      the administration of this conjugate vaccine concurrently with routine
      immunization in infants is planned.

PMID- 16425131
TI  - Urokinase-type plasminogen activator receptor plays a role in neutrophil
      migration during lipopolysaccharide-induced peritoneal inflammation but not
      during Escherichia coli-induced peritonitis.
AB  - BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is expressed on
      many different cells, including leukocytes. uPAR has been implicated to play a
      role in neutrophil migration to sites of inflammation. METHODS: To determine the
      role that uPAR plays in neutrophil recruitment in response to bacterial products
      or intact bacteria, uPAR gene-deficient (uPAR(-/-)) and wild-type (wt) mice were
      injected intraperitoneally with either Escherichia coli or lipopolysaccharide
      (LPS) derived from this bacterium. RESULTS: uPAR(-/-) mice demonstrated a
      decreased LPS-induced neutrophil migration into peritoneal lavage fluid, whereas
      the chemokine and cytokine response was unaltered. In contrast, during E. coli
      induced peritonitis, uPAR(-/-) mice had a normal neutrophil migration into the
      primary site of infection. The unaltered neutrophil trafficking in uPAR(-/-) mice
      during bacterial infection was corroborated by histological assessment of liver
      and lung tissue and myeloperoxidase levels in tissue homogenates. uPAR(-/-) mice
      displayed slightly but significantly lower bacterial loads in the peritoneal
      cavity, together with a decreased dissemination to the circulation early during
      the infection. CONCLUSION: These data suggest that uPAR, in part, mediates
      neutrophil migration into the peritoneal cavity on local instillation of LPS but
      that this function of uPAR can be compensated for during peritonitis caused by
      intact E. coli.

PMID- 16425132
TI  - The effect of bacille Calmette-Guerin vaccine strain and route of administration
      on induced immune responses in vaccinated infants.
AB  - Vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) has variable
      efficacy in preventing tuberculosis. Both BCG strain and route of administration
      have been implicated in determining efficacy; however, these variables are not
      considered in current clinical recommendations for vaccine choice. We evaluated
      antigen-specific immunity after percutaneous or intradermal administration of
      Japanese BCG or intradermal administration of Danish BCG. Ten weeks after
      vaccination of neonates, percutaneous Japanese BCG had induced significantly
      higher frequencies of BCG-specific interferon- gamma -producing CD4(+) and CD8(+)
      T cells in BCG-stimulated whole blood than did intradermal Danish BCG. Similarly,
      percutaneous vaccination with Japanese BCG resulted in significantly greater
      secretion of the T helper 1-type cytokines interferon- gamma, tumor necrosis
      factor- alpha , and interleukin-2; significantly lower secretion of the T helper
      2-type cytokine interleukin-4; and greater CD4(+) and CD8(+) T cell
      proliferation. Thus, BCG strain and route of neonatal vaccination confer
      different levels of immune activation, which may affect the efficacy of the
      vaccine.

PMID- 16425133
TI  - A controlled, household-randomized, open-label trial of the effect that treatment
      of Helicobacter pylori infection has on iron deficiency in children in rural
      Alaska.
AB  - BACKGROUND: Helicobacter pylori infection and iron deficiency are prevalent in
      disadvantaged populations worldwide. Previous small or uncontrolled studies have
      reported that successful treatment of H. pylori infection may resolve iron
      deficiency or anemia. METHODS: We screened 68% of children 7-11 years old living
      in 10 western Alaska villages. The 219 children with iron deficiency (serum
      ferritin level, <22.5 pmol/L [<10 microg/L]) and H. pylori infection (diagnosed
      on the basis of (13)C-labeled urea breath tests) were enrolled in a household
      randomized, unblinded trial. All children received iron supplementation for 6
      weeks; children in the intervention group also received a 2-week course of
      treatment for H. pylori infection plus another 2-week course of treatment if the
      infection had not resolved at 2 months after treatment initiation. RESULTS: At 2
      months after treatment initiation, 32% of children in the intervention group and
      39% of children in the control group had iron deficiency. At 14 months after
      treatment initiation, 65% of children in the intervention group and 72% of
      children in the control group had iron deficiency (adjusted relative risk [ARR],
      0.90 [95% confidence interval [CI], 0.74-1.1]); in addition, 22% of children in
      the intervention group and 14% of children in the control group had anemia (ARR,
      1.6 [95% CI, 0.86-2.9]). Results were similar when children were compared by H.
      pylori infection status. CONCLUSIONS: In a high-prevalence population, treatment
      and resolution of H. pylori infection did not improve isolated iron deficiency or
      mild anemia up to 14 months after treatment initiation.

PMID- 16425134
TI  - Comprehensive analysis of bacterial risk factors for the development of Guillain
      Barre syndrome after Campylobacter jejuni enteritis.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS), a postinfectious autoimmune-mediated
      neuropathy, is a serious complication after Campylobacter jejuni enteritis.
      METHODS: To investigate the bacterial risk factors for developing GBS, genotypes,
      serotypes, and ganglioside mimics on lipo-oligosaccharide (LOS) were analyzed in
      C. jejuni strains from Japanese patients. RESULTS: Strains from patients with GBS
      had LOS biosynthesis locus class A more frequently (72/106; 68%) than did strains
      from patients with enteritis (17/103; 17%). Class A strains predominantly were
      serotype HS:19 and had the cstII (Thr51) genotype; the latter is responsible for
      biosynthesis of GM1-like and GD1a-like LOSs. Both anti-GM1 and anti-GD1a
      monoclonal antibodies regularly bound to class A LOSs, whereas no or either
      antibody bound to other LOS locus classes. Mass-spectrometric analysis showed
      that a class A strain carried GD1a-like LOS as well as GM1-like LOS. Logistic
      regression analysis showed that serotype HS:19 and the class A locus were
      predictive of the development of GBS. CONCLUSIONS: The high frequency of the
      class A locus in GBS-associated strains, which was recently reported in Europe,
      provides the first GBS-related C. jejuni characteristic that is common to strains
      from Asia and Europe. The class A locus and serotype HS:19 seem to be linked to
      cstII polymorphism, resulting in promotion of both GM1-like and GD1a-like
      structure synthesis on LOS and, consequently, an increase in the risk of
      producing antiganglioside autoantibodies and developing GBS.

PMID- 16425135
TI  - Local and systemic cytokine levels in relation to changes in vaginal flora.
AB  - BACKGROUND: Bacterial vaginosis (BV) is associated with increased risk of
      obstetrical and gynecologic complications and acquisition of sexually transmitted
      diseases. Despite this, very little is known about the pathogenesis of this
      disease. METHODS: Interleukin (IL)-1 beta , tumor necrosis factor- alpha , IL-6,
      and IL-8 concentrations in vaginal wash and serum samples from women with normal
      flora, intermediate flora, and BV (determined by Nugent criteria) were measured
      by enzyme-linked immunosorbent assay. RESULTS: Cytokine levels were not different
      between women with intermediate flora and women with BV. Women with either
      intermediate flora or BV had significantly higher concentrations of IL-1 beta in
      vaginal wash samples than did women with normal flora. The presence of IL-1 beta
      in vaginal wash samples was associated with >30 Gardnerella or Prevotella
      morphotypes per high-power field, as detected by Gram staining of vaginal swab
      specimens. Variation in the numbers of Lactobacillus and Mobiluncus species did
      not influence local cytokine levels. Serum cytokine levels were not influenced by
      any changes in vaginal flora. CONCLUSIONS: Women with intermediate flora generate
      significant cytokine responses. It is possible that the risks associated with BV
      may also affect women with intermediate flora and that appropriate treatment may
      reduce such risk.

PMID- 16425136
TI  - Vigorous hepatitis C virus-specific CD4+ and CD8+ T cell responses induced by
      protein immunization in the presence of Montanide ISA720 plus synthetic
      oligodeoxynucleotides containing immunostimulatory cytosine-guanine dinucleotide
      motifs.
AB  - BACKGROUND: A prophylactic vaccine for hepatitis C virus (HCV) requires
      generation of strong humoral as well as CD4(+) and CD8(+) T cell responses.
      METHODS: The immunomodulatory effects of the combination of 2 adjuvants,
      synthetic oligodeoxynucleotides containing immunostimulatory cytosine-guanine
      dinucleotide motifs emulsified with Montanide ISA720 (M-ISA720/CpG), were
      investigated using the murine model. RESULTS: Administration of recombinant HCV
      (rHCV) nonstructural (NS) 3 and NS5B proteins plus M-ISA720/CpG (hereafter, "M
      ISA720/CpG/rHCV protein") induced high anti-NS3 and anti-NS5B immunoglobulin (Ig)
      G titers, with the IgG2a isotype being predominant. NS3- and NS5B-specific
      interferon (IFN)- gamma - and interleukin-2-producing CD4(+) T cell responses, as
      assessed by enzyme-linked immunospot assay, were significantly more vigorous in
      mice immunized with M-ISA720/CpG/rHCV protein than in control mice immunized
      without adjuvant. NS3- and NS5B-specific IFN- gamma -producing CD8(+) T cell
      percentages, as measured by direct ex vivo intracellular cytokine staining assay,
      were, respectively, a mean+/-SD of 0.14% +/- 0.04% and 0.15% +/- 0.05% in mice
      immunized with M-ISA720/CpG/rHCV protein. Furthermore, boosting with recombinant
      NS3 expression plasmid DNA after priming with M-ISA720/CpG-adjuvanted rNS3
      strikingly enhanced both CD4(+) and CD8(+) T cell responses. CONCLUSION:
      Immunization with M-ISA720/CpG/rHCV protein is capable of inducing potent humoral
      as well as HCV-specific T helper type 1-biased CD4(+) and CD8(+) T cell
      responses. A DNA boost after a protein prime--a reversal of the conventional
      approach--may provide an alternative path to the development of an effective HCV
      vaccine.

PMID- 16425137
TI  - The interferon antagonist NS2 protein of respiratory syncytial virus is an
      important virulence determinant for humans.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is targeted for vaccine
      development, because it causes severe respiratory tract illness in the elderly,
      young children, and infants. A primary strategy has been to derive live
      attenuated viruses for use in intranasally administered vaccines that will induce
      a protective immune response. In the present study, the NS2 gene, whose encoded
      protein antagonizes the host's interferon- alpha / beta response, was deleted
      from RSV vaccine candidates by use of reverse genetics. METHODS: Three NS2 gene
      deleted RSV vaccine candidates were studied: rA2cp Delta NS2, rA2cp248/404 Delta
      NS2, and rA2cp530/1009 Delta NS2. rA2cp Delta NS2, which had the fewest
      attenuating mutations, was evaluated in adults and RSV-seropositive children.
      rA2cp248/404 Delta NS2 and rA2cp530/1009 Delta NS2 were evaluated in adults and
      RSV-seropositive and RSV-seronegative children. RESULTS: At a high dose (10(7.0)
      pfu), rA2cp Delta NS2 was not shed by adults, and only 13% of them had an immune
      response. The other vaccine candidates, rA2cp248/404 Delta NS2 and rA2cp530/1009
      Delta NS2, had greatly decreased infectivity in RSV-seronegative children,
      compared with that of their immediate parent strains, which possess an intact NS2
      gene. CONCLUSIONS: Deletion of the NS2 gene attenuates RSV in subjects of all
      ages studied. This validates the strategy of developing live respiratory tract
      virus vaccines in which the virus's ability to inhibit the human innate immune
      system is blocked. rA2cp248/404 Delta NS2 should be studied in children at a
      higher input titer, because it was more infectious and immunogenic than was
      rA2cp530/1009 Delta NS2.

PMID- 16425138
TI  - Activation of synoviocytes by the secreted phospholipase A2 motif in the VP1
      unique region of parvovirus B19 minor capsid protein.
AB  - Parvovirus B19 infection in adults is often associated with acute symmetrical
      polyarthropathy, but the mechanism is unknown. Recently, a secreted phospholipase
      A(2) (sPLA(2)) motif was identified in the VP1-unique region (VP1u) of the B19
      minor capsid protein. To investigate the role of this motif, we expressed VP1u
      with and without point mutations in the critical amino acids of sPLA(2). Although
      high concentrations of B19 did not infect human fibroblast-like synoviocytes
      (HFLSs), there was a >3-fold increase in synoviocyte migration that could be
      blocked by phospholipase inhibitors. Recombinant proteins with intact VP1u
      demonstrated sPLA(2) activity and induced cell migration, whereas proteins with
      mutated VP1u were nonfunctional in both assays. The incubation of HFLSs with
      proteins that had intact VP1u, but not with proteins with mutated VP1u, increased
      the production of prostaglandin E(2) >100-fold. Expression of cyclooxygenase
      (COX)-2 mRNA transcripts, as determined by real-time reverse-transcription
      polymerase chain reaction, and COX-2 protein expression were both significantly
      increased after incubation with protein that had intact VP1u. Proteins with VP1u
      in noninfectious B19 may participate in the inflammatory response in the synovial
      compartment.

PMID- 16425139
TI  - Effect of maternal treatment with cyclic HPMPC in the guinea pig model of
      congenital cytomegalovirus infection.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection of the fetus is the leading cause of
      congenital infection. Using the guinea pig model of congenital CMV infection, we
      sought to determine whether antiviral treatment of a CMV-infected dam could
      improve the outcome of offspring. METHODS: Pregnant Hartley guinea pigs were
      inoculated with guinea pig CMV (GPCMV) during the late second/early third
      trimester of gestation. Guinea pigs received either 1 dose of cyclic 1-[((s)-2
      hydroxy-2-oxo-1,4,2,-dioxaphosphorinan-5-yl)methyl]cytosine dihydrate (cHPMPC; 35
      mg/kg) or placebo 24 h after GPCMV infection. Guinea pigs were monitored until
      delivery or were killed 10 days after infection, for the evaluation of the effect
      of cHPMPC on viral replication by polymerase chain reaction analysis in various
      dam and pup tissues. RESULTS: cHPMPC treatment of infected dams improved pup
      survival from 28.2% (11/39) to 83.7% (36/43) (P < .001) and extended the duration
      of pregnancy. cHPMPC treatment did not prevent infection of the placenta or
      disseminated infection of the dam and pup but significantly decreased the amount
      of GPCMV in tissues. GPCMV DNA levels in the placenta were reduced from 3.54 to
      2.12 log(10) genome copies/ mu g of DNA (P < .0001). CONCLUSIONS: Treatment of
      the GPCMV-infected pregnant dam with 1 dose of cHPMPC improves the outcome of
      congenital infection and decreases viral replication in a guinea pig model.

PMID- 16425140
TI  - 1,25-dihydroxyvitamin d3 enhances systemic and mucosal immune responses to
      inactivated poliovirus vaccine in mice.
AB  - 1,25-Dihydroxyvitamin D3 (DHVD3) coadministered with monovalent inactivated
      poliovirus vaccine (IPV) of all 3 serotypes significantly enhances antipoliovirus
      systemic and mucosal immunity in mice. Although serum immunoglobulin G antibodies
      are significantly higher in serotypes 2 and 3, and although salivary
      immunoglobulin A is significantly increased in serotypes 1 and 3, DHVD3 had the
      most dramatic effect on the level of neutralizing serum antibodies of all 3 IPV
      serotypes. These findings suggest a possible use of vitamin D3 as an adjuvant for
      currently used and proposed new Sabin IPVs.

PMID- 16425141
TI  - Antibody-dependent enhancement in dengue virus infections.

PMID- 16425142
TI  - Measuring dengue enhancing antibodies: caveats.

PMID- 16425144
TI  - Amplified HIV transmission during early-stage infection.

PMID- 16425146
TI  - Do human osteoblasts grow into open-porous titanium?
AB  - A titanium foam for spine fusion and other applications was tested by cell
      culture. Its high porosity and surface roughness should enable bone cells to grow
      through it, resulting in a better fixation of the vertebral body. The foam was
      tested by in vitro experiments with human osteoblasts under static culture
      conditions and in a perfused system. By means of cell number, viability, scanning
      electron microscopy and histological staining, cell proliferation could be
      observed. The expression of osteogenic genes like collagen-I, alkaline
      phosphatase and osteocalcin was proven by reverse transcription polymerase chain
      reaction (RT-PCR) as well as in the case of alkaline phosphatase with biochemical
      methods. The conducted experiments showed that human osteoblasts could grow
      through the interconnected porosity of the metal foam and that they expressed an
      osteoblast like phenotype. The results suggest that in vivo osteoblasts are
      likely to form a trabecular bone bridge through this titanium foam. Consequently,
      with this osteoconductive material, there may be a reduced need for autologous
      bone in spinal fusion procedures.

PMID- 16425147
TI  - The involvement of aggrecan polymorphism in degeneration of human intervertebral
      disc and articular cartilage.
AB  - The functions of the intervertebral disc and of articular cartilage are
      intimately related to their aggrecan content. Aggrecan is a proteoglycan that
      interacts with hyaluronan to form large aggregates, which are responsible for the
      ability of the tissues to resist compressive loads. This function is related to
      the structure of aggrecan, and in particular to the large number of chondroitin
      sulphate chains present on its core protein. The chondroitin sulphate chains are
      present in two adjacent regions of the aggrecan core protein, termed the CS1 and
      CS2 domains. In the human, the region of the aggrecan gene encoding the CS1
      domain exhibits size polymorphism, which can result in variation in the degree of
      chondroitin sulphate substitution of aggrecan in different individuals. This
      raises the possibility that the functional properties of aggrecan may vary
      between individuals, and that those individuals with an inferior aggrecan
      structure may be more susceptible to premature intervertebral disc or articular
      cartilage degeneration. Several studies have been performed to demonstrate such
      an association, but the results have been ambiguous. This review explains the
      relationship between aggrecan structure and function, describes the technique
      used to assess aggrecan polymorphism and the conclusions and limitations of the
      data obtained to date, and discusses the implications for tissue degeneration and
      clinical practice.

PMID- 16425148
TI  - Quantitative anatomy of the posterior cricoid region.
AB  - The anatomy of the posterior cricoid cartilage region was examined to obtain a
      better quantitative understanding of this region. The mean height and width of
      the posterior cricoid cartilage in the midline measured 24.5 mm and 25 mm
      respectively. The mean distance between the fibres for the left and right
      posterior cricoarytenoid muscles was 5 mm at the midpoint of the posterior
      cricoid cartilage. The height of these muscles averaged 19 mm for left sides and
      20 mm for right sides. The mean distances from the midpoint and superior midline
      of the posterior cricoid cartilage to the inferior laryngeal nerve were 14 mm and
      15 mm respectively for left sides and 17 mm and 18 mm respectively for right
      sides. It is hoped that these data will be of use to clinicians performing
      invasive procedures in this area.

PMID- 16425149
TI  - A new morphometric method for the sella turcica and the hypophyseal fossa and its
      clinical relevance.
AB  - The sella turcica and the hypophyseal fossa should be considered different
      entities, the latter being part of the former. Their morphology and dimensions
      correlate to some extent with those of the contained pituitary gland and have,
      for this reason, attracted the interest of anatomists and radiologists. With the
      application of MRI, however, these data are of limited use in the diagnosis of
      pituitary disorders, although they remain valuable with regard to a microsurgical
      approach to the hypophysis. The proposed morphometric method was applied to 20
      dry skulls. We first made casts of the corresponding sellae. Their volumes were
      then measured by immersion. The frontal section of each hypophyseal fossa was
      obtained through its deepest point and magnified. The Cartesian co-ordinates of
      the contour of the section were used to evaluate the corresponding area and
      centroid. The volume of each fossa was finally obtained by the use of Pappus'
      theorem applied to solids of rotation. The volumes of the sellae obtained as
      above ranged from 460 mm3 to 1570 mm3 with a mean value of 835 mm3. These figures
      are comparable to those reported from previous authors. To our knowledge the
      method described has enabled a close approximation of the volumes of the
      hypophyseal fossae to be made for the first time. These volumes ranged from 24
      mm3 to 300 mm3, with a mean value of 157 mm3. Similar numerical methods might be
      applicable in vivo by the use of MR imaging.

PMID- 16425150
TI  - Apoptosis in the course of experimetal intracerebral haemorrhage in the rat.
AB  - Intracerebral haematoma was produced in 25 adult rats by infusion of 100 microl
      of autologous blood into the striatum. The animals' brains were removed at 1, 3,
      7, 14 and 21 days after production of the haematoma. The TUNEL method was used to
      detect DNA fragmentation and TUNEL-positive cells were qualified. TUNEL-positive
      cells were already found on the first day of observation and were present for
      three weeks after haematoma production. These results provide evidence that
      programmed cell death is associated with intracerebral haemorrhage.

PMID- 16425151
TI  - Schwann units in the human foetal phrenic nerve.
AB  - In three human foetuses aged 15, 17, and 23 weeks the number of axons surrounded
      by single Schwann cells was counted. These Schwann cell/axon complexes form the
      Schwann units. The largest Schwann units in the foetus aged 15 weeks contained
      232 axons, in the foetus of 17 weeks the number was 140 and in the foetus of 23
      weeks the largest units contained 65 axons.

PMID- 16425152
TI  - The origin and relations of the anterior choroidal artery: an anatomical study.
AB  - There has recently been an increase in surgical interventions to the inferior
      temporal lobe. The aim of the present study is to examine the anatomical
      structure and relations of the anterior choroidal artery, which extends to this
      region. A mixture of latex and ink was injected into the internal carotid and
      basilar arteries of 15 brains from fresh cadavers. In 18 out of 30 cases (60%)
      the anterior choroidal artery arose from the posteroinferior aspect of the
      internal carotid artery, in 8 (22.2%) from the posterolateral aspect and in 4
      (2%) from its anterior part. The diameter of the anterior choroidal artery was
      0.94 mm on average (0.7-1.2) and the average distance from the posterior
      communicating artery was 5.3 mm (3.8-8 mm); its distance to the bifurcation of
      the carotid was found to be 4.0 mm on average (2.2-8 mm). The cisternal segment
      of the anterior choroidal artery and the optic tract formed a neurovascular
      bundle. The branches arising from the plexal segment supply the lateral
      geniculate body, the thalamus and the optic tract. The resulting knowledge of the
      neurovascular relations of the anterior choroidal artery provides a safe surgical
      approach to the inferior temporal lobe.

PMID- 16425153
TI  - In vivo gene transfer to the brain cortex using a single injection of HSV-1
      vector into the medial septum.
AB  - This study shows that an ICP4-replication-deficient herpes simplex virus
      containing the Moloney murine leukaemia virus LTR fused with the coding sequence
      for the beta-galactosidase gene can be used as a very effective vector for
      delivering the beta-galactosidase reporter gene into the rat brain septum. F344
      rats received bilateral stereotaxic injections into the nucleus of the diagonal
      band and into the medial septum. The X-gal stain was used to detect the activity
      of the expressed beta-galactosidase enzyme. The delivered reporter gene was
      expressed successfully not only in the neuronal cells of the injected areas but
      also in cells that project to the injection area such as cortex cells about 6 mm
      away from the injection sites. Expression was visible at 1, 3 and 9 weeks
      following injection. We conclude that this vector can effectively deliver genes
      into different regions of the mature mammalian brain and also to areas distant
      from the injection site.

PMID- 16425154
TI  - An electron microscopic study of the phosphatases in the ciliate Balantidium
      coli.
AB  - The localisation and activity of D glucose-6-phosphatase (G-6-Pase) and alkaline
      phosphatase (AlP) in the trophozoites of Balantidium coli isolated from pig
      intestine content were investigated using ultrastructural and cytochemical
      methods. The activity of G-6-Pase was demonstrated on the membranes of the
      endoplasmic reticulum, particularly in the cortical part of the trophozoites. In
      addition, the product of the reaction to G-6-Pase was concentrated in the
      vesicular structures, which were distributed along the reticular membranes. These
      structures were described as vesicles similar to glycosomes, containing enzymes
      of glycogenolysis. It is very likely that hydrolases in B. coli are formed on the
      rough reticular membranes without the involvement of cisterns of the Golgi
      complex. The ultrastructural deposits of the reaction to G-6-Pase and AlP in the
      trophozoites of B. coli described here indicate that some membranes of the rough
      endoplasmic reticulum and small vacuoles with a strong reaction to these enzymes
      can play a similar role to the Golgi complex.

PMID- 16425155
TI  - The topography of the superficial veins of the hind leg in the baboon Papio
      anubis in comparison with the superficial veins of the lower limb in humans.
AB  - Our studies were carried out on 8 male and 2 female baboons Papio anubis
      cadavers. We examined a total of 20 hind legs. The vessels of the hind leg were
      filled with coloured latex. Afterwards we prepared the superficial and deep veins
      and accompanying arteries. We paid attention to the location, diameter and the
      course of the long and short saphenous veins. We found many differences between
      the system of superficial veins in the baboon hind leg and that in the human
      lower limb. First of all, the long saphenous vein in the baboon Papio anubis
      presented as two similar trunks that ran together with a concomitant artery. The
      saphenofemoral junction was also duplicated. The distance between these outlets
      was about 4 mm and their location was different from that in humans. Neither
      trunk exceeded 2.5 m in diameter. Some human-like features were noticed in the
      system of the short saphenous vein in Papio anubis. The diameter of the short
      saphenous vein and its course and the location of the saphenopopliteal junction
      were very similar to those in humans. On the other hand, the short saphenous vein
      was the main superficial venous channel of the hind limb of Papio anubis.

PMID- 16425156
TI  - Changes in the morphology of the acinar cells of the rat pancreas in the
      oedematous and necrotic types of experimental acute pancreatitis.
AB  - Limited experimental models of the oedematous and necrotic types of acute
      pancreatitis provide some understanding of the pathophysiology of this disease.
      Wistar rats were treated with cerulein at 10 mg/kg of body weight or with L
      arginine at 1.5 or 3 g/kg of body weight in order to induce the oedematous or
      necrotic type of acute pancreatitis. After the induction period we examined
      samples of pancreata with light and electron microscopes. Morphological
      examination showed profound changes in the histology of the pancreas and its
      acinar cells and subcellular structures, especially in the group of rats which
      received a higher dose of L-arginine, amounting to 3 g/kg body weight. These
      included parenchymal haemorrhage and widespread acinar cell necrotic changes. 4
      OH-TEMPO successfully prevented morphological deterioration as well as amylase
      release, suggesting that the severity of the two types of disease strongly
      depends on the intensity of the oxidative stress. Our results lend support to the
      assumption that reactive oxygen species play an axial role in the pathogenesis of
      both types of acute pancreatitis.

PMID- 16425157
TI  - Mimicking of glutathione peroxidase deficiency by exposition of JAR cells to
      increased level of synthetic hydroperoxide.
AB  - A short chain synthetic analogue of lipid hydroperoxides was used to overload
      glutathione peroxidase (GPx) in human choriocarcinoma cell line JAR cells. Cells
      exposed to 100 microM tBuOOH displayed a 40% reduction in ATP level and
      significantly increased in membrane permeability, visualised by the lactate
      dehydrogenase (LDH) release into the extracellular medium. The intracellular
      level of oxygen free radicals measured as an oxidation of the dichlorodihydro
      fluorescein diacetate (H2DCF-DA) significantly increased after 2 hours of cell
      exposition to 100 microM tBuOOH. Concomitantly MDA, 4-HNE level increased to 2
      nmol/mg of cell protein after 2 hours. Mitochondria stained with MitoTracker Red
      CMXRos displayed a filamentous appearance in control cells but changed into
      granular less energised organelles after exposition to tBuOOH. Collectively, the
      above results indicate the importance of the contribution of oxidative stress in
      the development of pre-eclampsia.

PMID- 16425159
TI  - External diameters of the crural arteries in patients with chronic critical limb
      ischaemia.
AB  - Knowledge of the diameters of the crural arteries forms the basis for
      reconstructive vascular surgery and percutaneous angioplasty. The external
      diameters of the crural arteries were examined in 152 specimens of lower limbs by
      anatomical, digital and statistical methods. The diameters of all the crural
      arteries were significantly greater (p < or = 0.01) in the male subjects. The
      differences between the right and left arterial diameters were statistically
      significant (p < or = 0.01) only in relation to the posterior tibial artery. In
      subtypes IC and IIB the anterior tibial artery was the strongest, the peroneal
      artery was of intermediate diameter and the posterior tibial artery was the
      weakest. In subtype IB the anterior tibial artery presented as the predominant
      vessel but in subtypes IIA-1 and IIA-2 it was the posterior tibial artery that
      did so. In subtype IA 24 examples of the coexistence of angiometric variants of
      the crural arteries were distinguished. It was demonstrated that the strongest
      vessel was the anterior tibial artery (32.24%), rarely the posterior tibial
      artery (14.47%) or the peroneal artery (9.87%). In most cases (21.71%) three of
      the crural arteries had intermediate diameters. In 13.16% of cases there were two
      arteries of intermediate diameter, the posterior tibial and the peroneal, which
      accompanied a strong anterior tibial artery and, the least common variant
      (6.58%), two intermediate tibial arteries with a weak peroneal artery. A
      hyperplastic peroneal artery (6.59%) compensated for either the anterior tibial
      artery (1.98%) or the posterior tibial artery (4.61%).

PMID- 16425160
TI  - The results of compression forces applied to the isolated human calvaria.
AB  - Data for the force necessary to fracture the isolated calvaria (skull cap) are
      not available in the extant literature. Twenty dry adult calvaria were tested to
      failure quasistatically at the vertex using a 15-kN load cell. The forces
      necessary to fracture or cause diastasis of calvarial sutures were then
      documented and gross examination of the specimens made. Failure forces had a mean
      measurement of 2772 N. Initial fractures did not cross suture lines. Prior to
      complete destruction of the calvaria there were 7 specimens in which all sutures
      of the calvaria became diastatic, 6 specimens in which the calvaria became
      diastatic along only the coronal sutures, 2 specimens in which the calvaria
      became diastatic along only the sagittal suture and 5 specimens in which there
      were diagonal linear parietal bone fractures. Our hopes are that these data may
      contribute to the structural design of more safer protective devices for use in
      our society, assist in predicting injury and aid in the construction of treatment
      paradigms.

PMID- 16425158
TI  - The variability and morphometry of the brachiocephalic trunk in human foetuses.
AB  - In prenatal and pediatric cardiovascular surgery knowledge of the various
      arrangements of the aortic arch and its branches as well as the normative data
      are essential. The variability and morphometric features of the brachiocephalic
      trunk in 131 human foetuses (65 male, 66 female) ranging from 15 to 34 weeks of
      gestation were studied by means of anatomical, digital and statistical methods.
      In all the foetuses examined the left aortic arches were found to have three
      different arrangements. In 74.05% of cases the usual pattern of the aortic arch
      with its three main branches were observed. A common origin of the
      brachiocephalic trunk and left common carotid artery occurred in 20.61% of
      individuals. In 5.34% of cases the left vertebral artery was an additional vessel
      and arose from the aortic arch between the left common carotid and subclavian
      arteries. No significant gender differences were found with respect to the
      brachiocephalic trunk (p > or = 0.05). The developmental increase in length (r1 =
      0.78) and diameter (r2 = 0.83) correlated with a linear function but the increase
      in volume in relation to age corresponded to a quadratic function (r3 = 0.73).
      Our results show the largest increases in the brachiocephalic trunk according to
      the following parameters: the length - between the 4(th) and 5(th), and 7(th) and
      8(th) months, diameter - between the 8(th) and 9(th) months and volume - between
      the 4(th) and 5(th), and 7(th) and 9(th) months of gestation (p < or = 0.01). The
      present study constructs a normal range for the morphometric features of the
      foetal brachiocephalic trunk.

PMID- 16425162
TI  - An unusual crossed course of separately originating left circumflex and left
      anterior descending arteries with concomitant anomalies found in multi-slice
      computed tomography.
AB  - Coronary artery anomalies occur in approximately in 1-2% of the population. The
      split origin of branches of the left coronary artery is a relatively common
      anomaly, usually with no significant observable impairment of cardiac function.
      The application of multi-slice computed tomography (MSCT) for cardiac imaging is
      increasing and becoming, along with other techniques, a recognised method of
      examination of the coronary arteries. In the case presented we observed in an ECG
      gated MSCT the anomalous origin and proximal course of the arteries of the left
      sinus of Valsalva. The ostiae of both coronary arteries were located unusually:
      the ostium of the LAD was found posterior to the ostium of the LCx. Because of
      this, the proximal part of the LAD crossed the proximal part of the LCx
      superiorly. Furthermore, muscular bridges were found in the middle part and in
      the first diameter branch of the LAD. To our knowledge, this is the first case of
      a crossed course of the LCx and the LAD to be presented in the literature.
      Applications of MSCT in coronary imaging are presented in comparison with other
      diagnostic imaging methods. The advantages and limitations of MSCT as a
      diagnostic tool for anomalies of the coronary arteries are discussed.

PMID- 16425161
TI  - The distribution and structure of the lingual papillae on the tongue of the bank
      vole Clethrinomys glareolus.
AB  - The distribution and three-dimensional structure of the lingual papillae were
      studied by means of scanning electron microscopy. The elongated tongue in the
      bank vole is about 12 mm in length and about 3 mm in width. The characteristic
      features of the tongue are the median sulcus on the apex of the tongue,
      considerable narrowing in the body of the tongue and a well developed intermolar
      prominence. On the surface of the apex and body of the tongue three morphological
      types of the filiform papillae and fungiform papillae were observed. The
      intermolar prominence of the tongue is covered with conical and saw-like filiform
      papillae. On the posteriolateral margin of the intermolar prominence two foliate
      papillae were found. A single oval vallate papilla was situated in the median
      line of the anterior part of the root of the tongue. The posterior part of the
      lingual root is flat without papillae. The distribution and types of the lingual
      papillae found in the bank vole are similar to those in species of the Microtinae
      family.

PMID- 16425163
TI  - The left sternalis muscle variation detected during mastectomy.
AB  - The sternalis muscle variation is a well-known anatomical situation. It is
      present in 8.7% of women and 6.4% of men, although the incidence varies according
      to sex, race and ethnicity. During a left modified radical mastectomy operation
      on a 46-year-old female patient a sternalis muscle was detected on the pectoralis
      major muscle in the superficial fascia. It was in craniocaudal position and was
      parallel to the body of the sternum. The cylindrical muscle was approximately 8
      cm in length and 2 cm in diameter. Such variations are considered to have their
      origin in embryological development. Awareness of muscular variations and their
      identification is important both for procedure through the proper dissection
      planes during breast surgery and in radiological examination and follow-up.

PMID- 16425164
TI  - Split median nerve. A report of two cases.
AB  - Two variations of the median nerve described in the Lanz study as type 3
      anomalies were found during dissection. In the first case the median nerve splits
      in the cubital fossa and descends through the carpal tunnel to the palm of the
      hand. In the second of the reported cases the median nerve splits 45 mm before
      entering the carpal tunnel and is accompanied by a persistent median artery.
      Surgeons should take such variations into consideration in order to plan surgical
      approaches judiciously.

PMID- 16425165
TI  - A rare variation of the inferior alveolar artery with potential clinical
      consequences.
AB  - Variations of the inferior alveolar artery are seemingly quite rare, especially
      with regard to its origin from the maxillary artery. We present an unusual case
      of an inferior alveolar artery that originated from the external carotid artery.
      To the best of our knowledge, our case is one of only two reports of the inferior
      alveolar artery arising from the external carotid artery. The clinician who deals
      with the mandibular region should be aware of such a variation in the arterial
      architecture.

PMID- 16425166
TI  - Arterial, neural and muscular variations in the upper limb.
AB  - During our routine dissection studies we observed arterial, neural and muscular
      variations in the upper limbs of an adult male cadaver. In this case we observed
      the superficial brachial artery origination from the third part of the axillary
      artery, communications between the musculocutaneous and median nerves, variant
      formation of the brachial plexus, origination of the profunda brachii artery from
      the posterior circumflex humeral artery and supernumerary tendons of the abductor
      pollicis longus muscle. We think that such variations should be kept in mind
      during surgical and diagnostic procedures.

PMID- 16425167
TI  - Structural comparison of self-organized adlayers of ligands and their metal
      coordinated complexes on a Au(111) surface: an STM study.
AB  - Scanning tunneling microscopy (STM) was employed to investigate the adsorption of
      the linear-spacer-bridged ligands bis(pyrrol-2-yl-methyleneamine) (BPMB and
      BPMmB), and their Zn(II)-coordinated complexes, BPMB/Zn(II) and BPMmB/Zn(II),
      onto a Au(111) surface in 0.1 M HClO(4) solution. Both the ligands, with
      different spacer bridges, and their Zn(II) complexes adsorb onto the Au(111)
      surface and self-organize into highly ordered two-dimensional arrays. The
      complexes BPMB/Zn(II) and BPMmB/Zn(II) appear in helical and triangular
      conformations, respectively, consistent with their chemical structures. Although
      the metal complexes include ligands, the assembled structures and adlayer
      symmetries of the ligands and complexes are totally different. The structures and
      intramolecular features obtained by high-resolution STM imaging are discussed.
      The results should be important in fabricating surface supramolecular structures.

PMID- 16425168
TI  - Naphthalene amidine imide dyes by transamination of naphthalene bisimides.
AB  - Derivatives of naphthalene-1,4,5,8-tetracarboxylic acid with amidine structures
      have been prepared. The light absorption of the bisimide derivatives in the UV
      region is shifted to the visible for the amidine imides, which also fluoresce
      with a large Stokes shift. It has been shown how the bisimide-lactam
      rearrangement can be extended to amidine structures.

PMID- 16425169
TI  - Bridging mu-eta(5):eta(4)-coordination of an indenyl ligand and reductive
      coupling of diazabutadienes in the assembly of di- and tetranuclear mixed-valent
      ytterbium indenyldiazabutadiene complexes.
AB  - The redox reaction of [Yb(C(9)H(7))(2)(thf)(2)] with the diazabutadiene
      PhN==C(Me)--C(Me)==NPh (DAD) has been found to depend on the molar ratio of the
      reactants. Reaction in a 1:2 molar ratio affords the dinuclear mixed-valent
      complex [Yb(2)(mu-eta(5):eta(4)-C(9)H(7))(eta(5)-C(9)H(7))(2){mu-eta(4):eta(4)
      PhNC(Me)==C(Me)NPh}] containing an indenyl ligand with an unusual mu
      eta(5):eta(4) bridging coordination. Reaction of equimolar amounts of these
      compounds results in an organolanthanide-mediated reductive coupling of the DAD
      ligands and formation of the tetranuclear mixed-valent complex [Yb(2)(mu
      eta(5):eta(4)-C(9)H(7))(eta(5)-C(9)H(7))(2){mu-eta(4):eta(4)
      PhNC(CH(2))==C(Me)NPh}](2) with a novel tetradentate tetraimine ligand.

PMID- 16425170
TI  - An experimental and theoretical study of the mechanism of stannylcupration of
      alpha,beta-acetylenic ketones and esters.
AB  - The title reaction has been investigated by experimental and computational (DFT)
      techniques, and subsequently compared to the corresponding carbocupration
      reaction, with particular emphasis on the stereoselectivity. For stannylcupration
      of an ynone substrate, only the anti-addition product is observed, whereas for
      the corresponding ynoate substrate, the stereoselectivity can be affected by the
      reaction conditions: in the presence of methanol as proton donor, the initial syn
      addition product can be trapped, whereas a syn/anti mixture is obtained in a non
      protic solvent. This is in sharp contrast to the carbocupration of the same ynone
      substrate with a cyanocuprate (RCu(CN)Li), which is highly selective for syn
      addition. The product selectivities can be understood from a detailed
      computational characterization of the reaction paths, and in particular from the
      relative stabilities of the vinyl cuprate and allenolate intermediates. It is
      suggested that the stereodetermining step is protonation of vinyl cuprate
      intermediates.

PMID- 16425172
TI  - Analysis of structural changes in bleached keratin fibers (black and white human
      hair) using Raman spectroscopy.
AB  - To investigate the influence of bleaching treatments on keratin fibers, the
      structure of cross-sections at various depths of bleached human hair (black and
      white human hair) was directly analyzed without isolating the cuticle and cortex,
      using Raman spectroscopy. The S-S band intensity existing from the cuticle region
      to the center of cortex region of virgin white human hair decreased, while the S
      O band intensity at 1040 cm(-1), assigned to cysteic acid, increased by
      performing the bleaching treatment. Especially, the S-O band intensity of the
      cuticle region increased remarkably compared with that of the cortex region.
      Also, the amide III (unordered) band intensity in the cortex region increased,
      indicating that some of the proteins existing throughout the cortex region
      changed to the random coil form. Moreover, it has been found that the S-S band
      intensity existing from the cuticle region to the center of the cortex region of
      the virgin black human hair decreased remarkably, while the S-O band intensity
      increased significantly compared with that of the virgin white human hair by
      performing the bleaching treatment. From these experiments, we concluded that the
      melanin granules including metal ions act as a decomposition accelerator for the
      oxidizing agent, thereby leading to a higher level of disulfide (-SS-) group
      cleavage in the black human hair compared with that of the white human hair.

PMID- 16425171
TI  - Nature of base stacking: reference quantum-chemical stacking energies in ten
      unique B-DNA base-pair steps.
AB  - Base-stacking energies in ten unique B-DNA base-pair steps and some other
      arrangements were evaluated by the second-order Moller-Plesset (MP2) method,
      complete basis set (CBS) extrapolation, and correction for triple (T) electron
      correlation contributions. The CBS(T) calculations were compared with decade-old
      MP2/6-31G*(0.25) reference data and AMBER force field. The new calculations show
      modest increases in stacking stabilization compared to the MP2/6-31G*(0.25) data
      and surprisingly large sequence-dependent variation of stacking energies. The
      absolute force-field values are in better agreement with the new reference data,
      while relative discrepancies between quantum-chemical (QM) and force-field values
      increase modestly. Nevertheless, the force field provides good qualitative
      description of stacking, and there is no need to introduce additional pair
      additive electrostatic terms, such as distributed multipoles or out-of-plane
      charges. There is a rather surprising difference of about 0.1 A between the
      vertical separation of base pairs predicted by quantum chemistry and derived from
      crystal structures. Evaluations of different local arrangements of the 5'-CG-3'
      step indicate a sensitivity of the relative stacking energies to the level of
      calculation. Thus, describing quantitative relations between local DNA
      geometrical variations and stacking may be more complicated than usually assumed.
      The reference calculations are complemented by continuum-solvent assessment of
      solvent-screening effects.

PMID- 16425173
TI  - Effect of diethylsulfoxide on the thermal denaturation of DNA.
AB  - DNA thermal denaturation has been investigated in aqueous solutions of
      diethylsulfoxide (DESO) by means of UV-vis and densimetry methods. It is
      suggested that, on the one hand, the structural change of entire solutions and,
      on the other hand, a direct interaction of DESO with DNA are responsible for the
      observed peculiar behavior. The results obtained were compared with those of
      dimethylsulfoxide (DMSO), also known from literature.

PMID- 16425174
TI  - Assessment of adenyl residue reactivity within model nucleic acids by surface
      enhanced Raman spectroscopy.
AB  - We rank the reactivity of the adenyl residues (A) of model DNA and RNA molecules
      with electropositive subnano size [Ag]n+ sites as a function of nucleic acid
      primary sequences and secondary structures and in the presence of biological
      amounts of Cl- and Na+ or Mg2+ ions. In these conditions A is markedly more
      reactive than any other nucleic acid bases. A reactivity is higher in ribo (r)
      than in deoxyribo (d) species [pA>pdA and (pA)n>>(pdA)n]. Base pairing decreases
      A reactivity in corresponding duplexes but much less in r than in d. In linear
      single and paired dCAG or dGAC loci, base stacking inhibits A reactivity even if
      A is bulged or mispaired (A.A). dA tracts are highly reactive only when dilution
      prevents self-association and duplex structures. In d hairpins the solvent
      exposed A residues are reactive in CAG and GAC triloops and even more in ATC
      loops. Among the eight rG1N2R3A4 loops, those bearing a single A (A4) are the
      least reactive. The solvent-exposed A2 is reactive, but synergistic structural
      transitions make the initially stacked A residues of any rGNAA loop much more
      reactive. Mg2+ cross-bridging single strands via phosphates may screen A
      reactivity. In contrast d duplexes cross-bridging enables "A flipping" much more
      in rA.U pairs than in dA.T. Mg2+ promotes A reactivity in unpaired strands. For
      hairpins Mg2+ binding stabilizes the stems, but according to A position in the
      loops, A reactivity may be abolished, reduced, or enhanced. It is emphasized that
      not only accessibility but also local flexibility, concerted docking, and cation
      and anion binding control A reactivity.

PMID- 16425175
TI  - Appraisal of traditional and recently proposed relationships between the hard and
      soft dimensions of the nose in profile.
AB  - This paper tests six methods of predicting external nasal profile proportions,
      using the form and dimensions of the bony nasal (piriform) aperture. A sample of
      122 lateral cephalograms was measured and traced before each method was
      attempted, under blind conditions where appropriate. Error was assessed by
      comparing predicted to actual proportions. Methods used by the following authors
      were tested: Krogman and Iscan (1986 The Human Skeleton in Forensic Medicine,
      Springfield: C.C. Thomas), Gerasimov (1955 The Reconstruction of the Face on the
      Skull), Prokopec and Ubelaker (2002 Forensic Sci. Commun. 4:1-4), Macho (1986 J.
      Forensic Sci. 31:1391-1403), George (1987 J. Forensic Sci. 32:1305-1330), and
      Stephan et al. (2003 Am J. Phys. Anthropol. 122:240-250). The two-tangent method
      by Gerasimov (1955 The Reconstruction of the Face on the Skull) was found to
      perform best at predicting a point on the nasal tip on male and female
      preoperative subjects. The method of Krogman and Iscan (1986 The Human Skeleton
      in Forensic Medicine, Springfield: C.C. Thomas) performed poorly, as did the
      nasal profile determination method (Prokopec and Ubelaker 2002 Forensic Sci.
      Commun. 4:1-4). The other methods, all derived by a process of regression
      calculations, were shown to perform with variable accuracy on this sample,
      despite the age range and ethnicity of this sample closely resembling that of the
      samples from which these methods were derived.

PMID- 16425176
TI  - Endocranial cast of Hexian Homo erectus from South China.
AB  - In this paper, we present data on the morphological features and linear
      measurements for the Hexian Homo erectus and other comparative endocasts, in
      order to highlight variation during human brain evolution. The endocast of Hexian
      was reconstructed in 1982, and an endocranial volume of 1,025 ml was estimated.
      The geological age is about 412 ka, or roughly contemporaneous with the
      Zhoukoudian (ZKD) specimens. There are some differences between Hexian and the
      modern Chinese male endocasts in our sample, including low position of the
      greatest breadth, low maximum height, a well-marked and prominent frontal keel,
      the flat surface of the frontal lobes, prominent sagittal keel along the center
      frontal and parietal lobes, depressed Sylvian areas and parietal lobes
      superiorly, strong posterior projection of the occipital lobes, anterior position
      of the cerebellar lobes relative to the occipital lobes, and the relative
      simplicity of the meningeal vessels. Compared with the ZKD, Indonesian, and
      African Homo erectus specimens, Hexian has more morphological features in common
      with ZKD. Principal component analyses indicate that Hexian is closest to the ZKD
      Homo erectus compared with the modern Chinese and other Homo erectus, but its
      great breadth distinguishes it. Metric analyses show that the brain height,
      frontal breadth, cerebral height, frontal height, and parietal chord from Homo
      erectus to modern humans increased, while the length, breadth, frontal chord, and
      occipital breadth did not change substantially.

PMID- 16425177
TI  - Revision of the Fully technique for estimating statures.
AB  - The "anatomical" method of Fully (1956 Ann. Legale Med. 35:266-273) for
      reconstructing stature, involving the addition of skeletal elements from the
      calcaneus to the skull, has been increasingly used in anthropological and
      forensic contexts, but has undergone little systematic testing on samples other
      than the original sample used to develop the technique. The original description
      by Fully of the method also does not provide completely explicit directions for
      taking all of the necessary measurements. This study tested the accuracy and
      applicability of his method, and clarified measurement procedures. The study
      sample consisted of 119 adult black and white males and females of known
      cadaveric statures from the Terry Collection. Cadaveric statures were adjusted to
      living statures, following the recommendations of Trotter and Gleser (1952 Am. J.
      Phys. Anthropol. 10:469-514). We obtained the best results using maximum
      vertebral body heights (anterior to the pedicles) and measurement of the
      articulated talus and calcaneus height in anatomical position. Statures derived
      using the original Fully technique are strongly correlated with living statures
      in our sample (r = 0.96), but underestimate living stature by an average of about
      2.4 cm. Anatomical considerations also suggest that the correction factors
      applied by Fully to convert summed skeletal height to living stature are too
      small. New formulae are derived to calculate living stature from skeletal height.
      There is no effect of sex or ancestry on stature prediction. Resulting stature
      estimates are accurate to within 4.5 cm in 95% of the individuals in our sample,
      with no directional bias.

PMID- 16425178
TI  - Who's afraid of the big bad Wolff?: "Wolff's law" and bone functional adaptation.
AB  - "Wolff's law" is a concept that has sometimes been misrepresented, and frequently
      misunderstood, in the anthropological literature. Although it was originally
      formulated in a strict mathematical sense that has since been discredited, the
      more general concept of "bone functional adaptation" to mechanical loading (a
      designation that should probably replace "Wolff's law") is supported by much
      experimental and observational data. Objections raised to earlier studies of bone
      functional adaptation have largely been addressed by more recent and better
      controlled studies. While the bone morphological response to mechanical strains
      is reduced in adults relative to juveniles, claims that adult morphology reflects
      only juvenile loadings are greatly exaggerated. Similarly, while there are
      important genetic influences on bone development and on the nature of bone's
      response to mechanical loading, variations in loadings themselves are equally if
      not more important in determining variations in morphology, especially in
      comparisons between closely related individuals or species. The correspondence
      between bone strain patterns and bone structure is variable, depending on
      skeletal location and the general mechanical environment (e.g., distal vs.
      proximal limb elements, cursorial vs. noncursorial animals), so that
      mechanical/behavioral inferences based on structure alone should be limited to
      corresponding skeletal regions and animals with similar basic mechanical designs.
      Within such comparisons, traditional geometric parameters (such as second moments
      of area and section moduli) still give the best available estimates of in vivo
      mechanical competence. Thus, when employed with appropriate caution, these
      features may be used to reconstruct mechanical loadings and behavioral
      differences within and between past populations.

PMID- 16425179
TI  - Insights into the "isolation" of the Basques: mtDNA lineages from the historical
      site of Aldaieta (6th-7th centuries AD).
AB  - We analyzed the hypervariable region I (HVR-I) sequence variability of the
      mitochondrial DNA (mtDNA) of individuals buried at Aldaieta (6th-7th centuries
      AD) in order to find out more about the biosocial implications of this cemetery.
      The results, fully authenticated by means of diverse criteria (analysis of
      duplicates, replication in an independent laboratory, quantification of target
      DNA, and sequencing and cloning of polymerase chain reaction products), suggest
      that Aldaieta largely consists of autochthonous individuals who shared common
      funereal customs with the late Ancient North Pyrenean cemeteries of Western
      Europe (the Reihengraberfelder), a cultural influence possibly accompanied by a
      certain genetic flow. Furthermore, the distribution of mtDNA lineages in the
      cemetery highlighted the existence of a significant number of family
      relationships, supporting the belief that it was a stable settlement and not a
      group that had haphazardly settled in the area. Finally, this paper stresses the
      importance of ancient DNA data for reconstructing the biological history of human
      populations, rendering it possible to verify certain hypotheses based solely on
      current population data. The presence at Aldaieta of an mtDNA lineage originating
      in Northwest Africa testifies to the existence of contact between the Iberian
      Peninsula and Northwest Africa prior to the Moorish occupation. Both this latter
      discovery and the high frequency of haplogroup J at the Aldaieta cemetery raise
      questions about the generally accepted belief that, since ancient times, the
      influence of other human groups has been very scarce in the Basque Country.

PMID- 16425181
TI  - The uncertainty principle of urodynamics.

PMID- 16425180
TI  - Linker chains of the gigantic hemoglobin of the earthworm Lumbricus terrestris:
      primary structures of linkers L2, L3, and L4 and analysis of the connectivity of
      the disulfide bonds in linker L1.
AB  - The extracellular hemoglobin (Hb) of the earthworm, Lumbricus terrestris, has
      four major kinds of globin chains: a, b, c, and d, present in equimolar
      proportions, and additional non-heme, non-globin scaffolding chains called
      linkers that are required for the calcium-dependent assembly of the full-sized
      molecule. The amino acid sequences of all four of the globin chains and one of
      the linkers (L1) have previously been determined. The amino acid sequences via
      cDNA of each of the three remaining linkers, L2, L3, and L4, have been determined
      so that the sequences of all constituent polypeptides of the hemoglobin are now
      known. Each linker has a highly conserved cysteine-rich segment of approximately
      40 residues that is homologous with the seven ligand-binding repeats of the human
      low-density lipoprotein receptor (LDLR). Analysis of linker L1 shows that the
      connectivity of the three disulfide bonds is exactly the same as in the LDLR
      ligand-binding repeats. The presence of a calcium-binding site comprising one
      glutamyl and three aspartyl residues in both the LDLR repeats and in the linkers
      supports the suggestion that calcium is required for the folding and disulfide
      connectivity of the linkers as in the LDLR repeats. Linker L2 is markedly
      heterogeneous and contains unusual glycine-rich sequences near the NH2-terminus
      and a polar zipper-like sequence with imperfect repeats of Asp-Asp-His at the
      carboxyl terminus. Similar Asp-Asp-His repeats have been found in a protein
      homologous to superoxide dismutase in the hemolymph of certain mussels. These
      repeats may function as metal-binding sites.

PMID- 16425183
TI  - Quantification of alpha1-adrenoceptor subtypes by real-time RT-PCR and
      correlation with age and prostate volume in benign prostatic hyperplasia
      patients.
AB  - BACKGROUND: We used a real-time reverse transcriptase polymerase chain reaction
      (RT-PCR) method for quantification of each alpha(1)-adrenoceptor (alpha(1)-AR)
      subtype expression level, and examined whether age and prostate volume influence
      human prostate alpha(1)-AR subtype expression. METHODS: Enrolled in our study
      were 75 men with lower urinary tract symptoms (LUTS) secondary to untreated
      benign prostatic hyperplasia (BPH). Real-time RT-PCR was performed using prostate
      biopsy specimens to quantify the expression level of each alpha(1)-AR subtype.
      RESULTS: The median expression level (interquartile range) was 1.24 (0.66-2.32),
      0.16 (0.10-0.33), and 1.11 (0.75-2.27) x 1,000 copies/beta-actin for alpha(1a)-,
      alpha(1b)-, and alpha(1d)-AR mRNA, respectively. The expression levels differed
      with the individual. The expression levels of alpha(1a)-AR, alpha(1d)-AR, and
      total alpha(1)-AR mRNA showed a significant positive correlation with patient
      age, but did not correlate with prostate volume. CONCLUSION: The difference in
      the expression of the alpha(1)-AR subtype with the patient may be the cause of
      the difference in the effectiveness of several subtype-selective alpha(1)-AR
      antagonists from patient to patient. The increase of alpha(1)-AR mRNA expression
      level with age could be an important factor in the pathogenesis of clinically
      significant BPH.

PMID- 16425182
TI  - Tumor-related immunity in prostate cancer patients treated with human recombinant
      granulocyte monocyte-colony stimulating factor (GM-CSF).
AB  - BACKGROUND: Granulocyte monocyte-colony stimulating factor (GM-CSF) supports the
      survival, expansion, and differentiation of lymphoid and myeloid derived
      dendritic cells (DCs). We hypothesized that systemic therapy with GM-CSF in
      prostate cancer patients could augment prostate cancer-related immunity and
      induce clinical response. METHODS: Eligible patients were randomly assigned to
      receive either 125 or 250 microg/m(2) GM-CSF subcutaneously three times a week
      until clinical progression. Prostate-specific antigen (PSA) T cell precursor
      frequencies were determined by a flow cytometric method. RESULTS: We were able to
      show, for the first time, a statistically significant correlation between pre
      treatment PSA level and PSA-specific CD4(+) T cell precursors and a trend between
      pre-treatment PSA level and PSA-specific CD8(+) T cell precursors (P<0.0001 and
      P=0.059, respectively). CONCLUSIONS: These results suggest that existent immunity
      to PSA in prostate cancer patients may be a promising target for future
      immunotherapeutic approaches to prostate cancer.

PMID- 16425184
TI  - PI3K/Akt signaling regulates p27(kip1) expression via Skp2 in PC3 and DU145
      prostate cancer cells, but is not a major factor in p27(kip1) regulation in LNCaP
      and PC346 cells.
AB  - BACKGROUND: We compared the involvement of PI3K/PTEN/Akt signaling in the
      regulation of the cell-cycle regulator p27(kip1) and investigated the mechanism
      of PI3K/PTEN/Akt modulation of p27(kip1) in the prostate cancer cell lines LNCaP,
      PC346, PC3, and DU145. METHODS: PI3K/PTEN/Akt signaling was manipulated by
      wortmannin or specific siRNA. The effects on PI3K/Akt downstream effectors and
      p27(kip1) expression were monitored on RNA and protein levels. RESULTS: PI3K/Akt
      inhibition in LNCaP and PC346 cells hardly affected p27(kip1) expression. As
      shown in LNCaP cells, p27(kip1) expression inversely correlated with Skp2
      expression, but Skp2 was not regulated by Akt. Blocking PI3K/Akt signaling in PC3
      cells resulted in decreased Skp2 protein expression and increased p27(kip1).
      Downregulation of PTEN in DU145 cells also showed PTEN/Akt-dependent regulation
      of Skp2 and p27(kip1). CONCLUSIONS: In PC3 and DU145 cells, Skp2 is the main
      determinant in the PI3K/Akt-dependent regulation of p27(kip1). In LNCaP and PC346
      cells, PI3K/Akt signaling is not a major factor in p27(kip1) regulation.

PMID- 16425185
TI  - Complete regression of experimental prostate cancer in nude mice by repeated
      hyperthermia using magnetite cationic liposomes and a newly developed solenoid
      containing a ferrite core.
AB  - BACKGROUND: Magnetite cationic liposomes (MCLs) can be used to induce
      hyperthermia because they generate heat in an alternating magnetic field (AMF).
      This study aimed at developing more practical method for MCL hyperthermia
      examining the effect of MCL-induced hyperthermia on human prostate cancer in
      vivo. MATERIALS AND METHODS: A newly developed AMF generator incorporating a
      solenoid with a ferrite core (FC) was used. Human prostate cancer cells (PC-3 and
      LNCap) were injected subcutaneously into nude mice. MCLs were injected into tumor
      nodule and the mice were exposed into AMF three times at 24-hr intervals
      (repeated hyperthermia; RH) until complete tumor regression was observed.
      RESULTS: Irradiation with an AMF generated by newly developed device can
      adequately increase the temperature of tumor tissue. Frequent RH resulted in
      complete tumor regression in all nude mice. CONCLUSION: RH using MCLs may be a
      promising new therapy for hormone-refractory human prostate cancer in the future.

PMID- 16425186
TI  - Lymphocytapheresis in the treatment of psoriasis vulgaris.
AB  - Psoriasis is a common autoimmune chronic inflammatory skin disease that affects
      approximately 2% of the world's population; fundamental for its immunopathogenic
      mechanism is secretion of type 1 (Th1) cytokines by T cells and their activation.
      Since cytapheresis has been widely applied to autoimmune disorders, emphasizing
      the recently reported results of granulocyte and monocyte adsorption apheresis in
      psoriasis, a small series of psoriasis vulgaris (PV) patients underwent
      lymphocytapheresis (LCA) with the aim to remove lymphocytes. Five patients were
      submitted to weekly LCA. The severity of the disease had been evaluated through
      psoriasis area and severity index (PASI) score before LCA and one week after the
      last apheresis. PASI score before: patient A: 66; patient B: 33; patient C: 50;
      patient D: 56; patient E: 29. All the patients showed improvement of skin
      lesions. PASI score after LCA: patient A: 24; patient B: 8; patient C: 5; patient
      D: 36; patient E: 2.1. No side effects linked to apheresis were reported. LCA
      seems to produce interesting results in PV, and PASI improvement related to
      apheresis is clinically significant. Further studies to address its mechanism of
      action and potential long-term side effects are needed. It could become a
      valuable therapeutic alternative or a complementary tool, which might even be
      used to reduce the dosages of conventional pharmacological therapies adopted for
      this chronic disease.

PMID- 16425187
TI  - Do mandibular cross-sectional properties and dental microwear give similar
      dietary signals?
AB  - Previous animal experimental work evaluating the effects of dietary consistency
      on mastication was generally limited to studies of either mandibular structure or
      rates and types of tooth wear. Control groups fed hard diets (HD) consistently
      exhibited increased cortical remodeling and/or bone strength when compared to
      groups fed soft diets (SD). Results of tooth-wear studies showed faster rates of
      tooth wear in HD animals. This study evaluates the effects of dietary differences
      on both mandibular structural morphology and postcanine dental microwear in the
      same animals. We examined mandibles and dentitions from eight miniature swine,
      raised from 4 weeks to 9 months of age on HD and SD (n = 4, each group).
      Mandibular structural properties were calculated from peripheral quantitative
      computed tomography slices at the dp3-dp4 and dp4-M1 junctions. Dental microwear
      analysis was performed on mandibular lingual crushing facets of dp4 and M1, using
      photomicrographs of high-resolution casts taken at 500x magnification in a
      scanning electron microscope. Our results suggest that between the dp3-dp4
      contact, HD animals have mandibles that are stronger and more rigid
      mediolaterally than SD animals. At the dp4-M1 contact, HD animals have mandibles
      that are stronger and more rigid mediolaterally, dorsoventrally, and in torsion
      than SD animals. Dental microwear results indicate that SD pigs have higher
      incidences of pitting and more overall microwear features on their premolars than
      do HD pigs, yet there are no significant differences in molar microwear
      morphology between the dietary groups. Near-significant correlations exist
      between pit size and dorsoventral bending strength, but only for HD pigs. These
      results suggest that dietary consistency significantly affects both mandibular
      structure and dental microwear, yet direct correlations between the two are
      complicated by a number of factors.

PMID- 16425189
TI  - A cranial base of Australopithecus robustus from the hanging remnant of
      Swartkrans, South Africa.
AB  - SKW 18, a partial hominin cranium recovered from the site of Swartkrans, South
      Africa, in 1968 is described. It is derived from ex situ breccia of the Hanging
      Remnant of Member 1, dated to approximately 1.5-1.8 Mya. Although partially
      encased in breccia, it was refit to the facial fragment SK 52 (Clarke 1977 The
      Cranium of the Swartkrans Hominid SK 847 and Its Relevance to Human Origins,
      Ph.D. dissertation, University of the Witwatersrand, Johannesburg), producing the
      composite cranium SKW 18/SK 52. Subsequent preparation revealed the most complete
      cranial base attributable to the species Australopithecus robustus. SKW 18
      suffered weathering and slight postdepositional distortion, but retains
      considerable anatomical detail. The composite cranium most likely represents a
      large, subadult male, based on the incomplete fusion of the spheno-occipital
      synchondrosis; unerupted third molar; pronounced development of muscular
      insertions; and large teeth. Cranial base measures of SKW 18 expand the range of
      values previously recorded for A. robustus. SKW 18 provides information on
      anatomical features not previously visible in this taxon, and expands our
      knowledge of morphological variability recognizable in the cranial base.
      Morphological heterogeneity in the development of the prevertebral and nuchal
      muscular insertions is likely the result of sexual dimorphism in A. robustus,
      while differences in cranial base angles and the development of the
      occipital/marginal sinus drainage system cannot be attributed to size dimorphism.

PMID- 16425191
TI  - Auricular surface aging: worse than expected? A test of the revised method on a
      documented historic skeletal assemblage.
AB  - This study presents results and recommendations arising from a blind test of the
      revised age estimation method for the auricular surface as proposed by Buckberry
      and Chamberlain ([2002] Am. J. Phys. Anthropol. 119:321-329). Auricular surfaces
      of 167 individuals from St. Bride's, London, a documented skeletal assemblage
      spanning the late 17th to early 19th century, were analyzed for the following
      traits: transverse organization, surface texture appearance, macroporosity,
      microporosity, and morphological changes to the apex. Composite scores of trait
      expressions were found to generally correlate with age and to show a positive
      association with known chronological age (P < 0.01). However, when composite
      scores were combined to define auricular surface phases, which ultimately assign
      age estimations, only three distinct developmental stages, compared with seven
      suggested by Buckberry and Chamberlain ([2002] Am. J. Phys. Anthropol. 119:321
      329), could be identified and statistically supported, all showing a considerable
      degree of individual variation in age. The most well-defined stage in the St.
      Bride's assemblage was the new stage III, where the majority of individuals were
      older than 60 years, whereas middle-aged adults displayed a large variation in
      composite scores. These results provide little hope for a promising application
      of age-at-death estimation of auricular surface morphology traits with higher
      resolution, but rather suggest indications of broad stages of life.

PMID- 16425190
TI  - Forelimb and hindlimb forces in walking and galloping primates.
AB  - One trait that distinguishes the walking gaits of most primates from those of
      most mammalian nonprimates is the distribution of weight between the forelimbs
      and hindlimbs. Nonprimate mammals generally experience higher vertical peak
      substrate reaction forces on the forelimb than on the hindlimb. Primates, in
      contrast, generally experience higher vertical peak substrate reaction forces on
      the hindlimb than on the forelimb. It is currently unclear whether this unusual
      pattern of force distribution characterizes other primate gaits as well. The
      available kinetic data for galloping primates are limited and present an
      ambiguous picture about peak-force distribution among the limbs. The present
      study investigates whether the pattern of forelimb-to-hindlimb force distribution
      seen during walking in primates is also displayed during galloping. Six species
      of primates were video-recorded during walking and galloping across a runway or
      horizontal pole instrumented with a force-plate. The results show that while the
      force differences between forelimb and hindlimb are not significantly different
      from zero during galloping, the pattern of force distribution is generally the
      same during walking and galloping for most primate species. These patterns and
      statistical results are similar to data collected during walking on the ground.
      The pattern of limb differentiation exhibited by primates during walking and
      galloping stands in contrast to the pattern seen in most nonprimate mammals, in
      which forelimb forces are significantly higher. The data reported here and by
      Demes et al. ([1994] J. Hum. Evol. 26:353-374) suggest that a relative reduction
      of forelimb vertical peak forces is part of an overall difference in locomotor
      mechanics between most primates and most nonprimate mammals during both walking
      and galloping.

PMID- 16425188
TI  - Brief communication: mitochondrial DNA variation suggests extensive gene flow
      from Polynesian ancestors to indigenous Melanesians in the northwestern Bismarck
      Archipelago.
AB  - Archaeological, linguistic, and genetic studies show that Austronesian (AN)
      speaking Polynesian ancestors came from Asia/Taiwan to the Bismarck Archipelago
      in Near Oceania more than 3,600 years ago, and then expanded into Remote Oceania.
      However, it remains unclear whether they extensively mixed with indigenous
      Melanesians who had populated the Bismarck Archipelago before their arrival. To
      examine the extent of admixture between Polynesian ancestors and indigenous
      Melanesians, mitochondrial DNA (mtDNA) variations in the D-loop region and the
      cytochrome oxidase and lysine transfer RNA (COII/tRNA(Lys)) intergenic 9-bp
      deletion were analyzed in the following three Oceanian populations: 1) Balopa
      Islanders as AN-speaking Melanesians living in the northwestern end of the
      Bismarck Archipelago, 2) Tongans as AN-speaking Polynesians, and 3) Gidra as non
      Austronesian-speaking Melanesians in the southwestern lowlands of Papua New
      Guinea. Phylogenetic analysis of mtDNA sequences revealed that more than 60% of
      mtDNA sequences in the Balopa Islanders were very similar to those in Tongans,
      suggesting an extensive gene flow from Polynesian ancestors to indigenous
      Melanesians. Furthermore, analysis of pairwise difference distributions for the D
      loop sequences with the 9-bp deletion and the Polynesian motif (i.e., T16217C,
      A16247G, and C16261T) suggested that the expansion of Polynesian ancestors
      possessing these variations occurred approximately 7,000 years ago.

PMID- 16425192
TI  - Relationship between formation of the femoral bicondylar angle and trochlear
      shape: independence of diaphyseal and epiphyseal growth.
AB  - During hominin evolution, an increase in the femoral bicondylar angle was the
      initial change that led to selection for protuberance of the lateral trochlear
      lip and the elliptical profile of the lateral condyle. No correlation is found
      during ontogeny between the degree of femoral obliquity and of the prominence of
      the lateral trochlear lip. Might there be a relationship with the elliptical
      profile of the lateral condyle? On intact femoral diaphyses of juvenile humans
      and great apes, we compared the anteroposterior length of the lateral and medial
      sides of the distal metaphysis. The two diaphyseal pillars remain equal during
      postnatal growth in great apes, while the growth of the lateral pillar far
      exceeds that of the medial pillar in humans. Increase in bicondylar angle is
      correlated with disproportionate anteroposterior lengthening of the lateral
      pillar. The increased anteroposterior length of the lateral side of the
      metaphysis would contribute to increasing the radius of the curvature of the
      lateral condyle, but not to the projection of the lateral trochlear lip. The
      similar neonatal and adult femoro-patellar joint shape in humans prompted an
      assessment of the similarity during growth of the entire neonatal and adult
      epiphyses. We showed that the entire epiphysis undergoes drastic changes in
      proportions during postnatal growth. Finally, we emphasize the need to
      distinguish the cartilaginous phenotype and the ossified phenotype of the distal
      femoral epiphysis (and of any epiphysis) during postnatal growth. This crucial
      distinction applies to most postcranial bones, for they almost all develop
      following the process of endochondral ossification.

PMID- 16425193
TI  - Midpoint CD34 measurement as a predictor of PBPC product yield in pediatric
      patients undergoing high-dose chemotherapy.
AB  - High-dose chemo/radiotherapy of sensitive tumors requires PBPC rescue doses of >3
      x 10(6) CD34/kg (range: 3-20 x 10(6) CD34/kg). Because of the diversity of stem
      cell treatment protocols and clinical presentation of patients at the time of
      peripheral blood progenitor cell (PBPC) harvest, the use of the mid-point CD34
      positive cell measurement was initiated to predict the final CD34-positive cell
      product yield/stem cell harvest. The measurement of CD34-positive cells at the
      mid-point of the initial setting of 5 total blood volumes (TBV) allows for the
      extension, shortening, or no change in the TBV processing to achieve a maximum
      goal of CD34-positive cells/kg body weight required for stem cell
      transplantation. The estimation of mid-point CD34-positive cells guided our
      center to extend 22 procedures, shorten 26 procedures, and leave 20 procedures
      unchanged. This investigation addresses three aspects of PBPC collection in
      pediatric patients: (1) the processing of large blood volumes (more than the
      defined 3 TBV and maximum up to 13 TBV in one session) to achieve good efficiency
      of the procedure; (2) the use of the mid-point CD34 measurement at 2.5 of 5 TBV
      initially set to predict the maximum goal of CD34 cells /kg needed on the same
      day of PBPC collection; and (3) PBPC collection in pediatric patients <10 kg body
      weight (as low as 5.8 kg body weight).

PMID- 16425194
TI  - Testosterone in juvenile and adolescent male chimpanzees (Pan troglodytes):
      effects of dominance rank, aggression, and behavioral style.
AB  - Testosterone is a steroid hormone with diverse effects on male reproductive
      function and behavior. The relationship between testosterone and social behavior
      such as mating and aggression has been investigated in a variety of primate
      species, but few such studies have been conducted on chimpanzees, and even fewer
      on primates during the juvenile and adolescent periods. This study explores the
      relationship between baseline urinary testosterone and behavioral variables
      including dominance rank, rates of aggression toward peers, and behavioral style
      in 16 juvenile and adolescent male chimpanzees (Pan troglodytes) living at the
      New Iberia Research Center in Louisiana. Behavioral observations and urine
      collection occurred during four research periods, each a year apart. After
      correcting for the positive association between testosterone and age,
      testosterone was positively associated with both dominance rank and rates of
      aggression directed at others. It was negatively associated with rates of
      aggression received. Individuals scoring highest in the "mellow" behavioral style
      component showed higher levels of testosterone than individuals scoring lowest in
      this component, an effect that may be partially due to the confounding effect of
      rank. The results of this study suggest that hormonal changes during the period
      preceding adulthood are not simply programmed physiological processes tied
      primarily to age-related change, but that important age-independent relationships
      with behavior also exist.

PMID- 16425195
TI  - Tailored strategy for AML patients receiving allogeneic peripheral blood stem
      cell transplantation.
AB  - Considering the heterogeneity of acute myelogenous leukemia (AML), along with the
      pros and cons of allogeneic peripheral blood stem cell transplantation (PBSCT), a
      tailored strategy is needed to minimize the transplant-related mortality and
      maximize the transplant outcomes in AML patients exhibiting certain factors that
      have an impact on the post-transplant quality of life and outcomes. The factors
      that need to be considered when tailoring a strategy in an allogeneic PBSCT
      setting include the recipient's performance status and co-morbid disease include
      AML risk stratification, disease status, expected severity of graft-versus-host
      disease, and the necessity of a graft-versus-leukemia effect. Accordingly, this
      review article describes a possible tailoring strategy for AML patients receiving
      allogeneic PBSCT based on certain factors influencing the transplant outcome.

PMID- 16425196
TI  - Dental morphology and the population history of the Pacific rim and basin:
      commentary on Hirofumi Matsumura and Mark J. Hudson.

PMID- 16425197
TI  - Lipid signaling changes in smooth muscle remodeling associated with partial
      urinary bladder outlet obstruction.
AB  - AIMS: Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated
      with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth
      muscle (DSM) reveals altered contractile characteristics. In this study, we
      analyzed the lipid-dependent signaling system that includes phospholipase A2 in
      PBOO-induced DSM remodeling and hypertrophy to determine whether the release of
      arachidonic acid (AA) from phospholipid is altered in the detrusor. METHODS:
      Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the
      urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder
      function was studied by keeping the rabbits in metabolic cages for 24 hr.
      Bladders were removed from rabbits that had bladder dysfunction (increased
      urinary frequency and decreased void volume) and the DSM separated from mucosa
      and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate
      the cytoplasmic AA. The level of AA release was compared with the level obtained
      with 2-week sham-operated rabbits. RESULTS: The rate of AA release was high in
      DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release
      in control DSM but DSM from obstructed rabbits revealed no further increase from
      the elevated basal AA release. The half-maximal concentration of carbachol that
      was required to stimulate AA release from control samples of detrusor was 35
      microM. CONCLUSIONS: The increased levels of AA release that are observed in this
      tissue after PBOO indicate the activation of phospholipase A2. The finding that
      carbachol could induce contraction, but not an increase in AA, indicates that the
      carbachol-induced contraction in the obstructed bladders is independent of lipid
      signaling pathways that involve AA. It is possible that the increased rate of
      arachidonic acid release from obstructed bladders correlates with the enhanced
      rates of prostaglandin production reported by other investigators from the same
      tissue.

PMID- 16425198
TI  - In vivo magnetic resonance volumetric and spectroscopic analysis of mouse
      prostate cancer models.
AB  - BACKGROUND: Mouse prostate cancer modeling presents unique obstacles to the study
      of spontaneous tumor initiation and progression due to the anatomical location of
      the tissue. RESULTS: High resolution (130 microm(x) x 130 microm(y) x 300
      microm(z)), three-dimensional MRI allowed for the visualization, segmentation,
      and volumetric measurement of the prostate from normal and genetically engineered
      animals, in vivo. Additionally, MRS performed on the prostate epithelia of
      probasin-ErbB-2Delta x Pten(+/-) mice identified changes in the relative
      concentrations of the metabolites choline and citrate, which was not observed in
      TRAMP mice. METHODS: T1-weighted MRI was performed on normal, TRAMP, probasin
      ErbB-2/Her2/Neu (probasin-ErbB-2Delta), and probasin-ErbB-2Delta in the context
      of decreased Pten activity (probasin-ErbB-2Delta x Pten(+/-)) mice. Volume
      localized single-voxel proton magnetic resonance spectroscopy (SVS (1)H MRS) was
      also performed. CONCLUSIONS: The data presented supports the use of combined MRI
      and MRS for the measurement of biochemical and morphometric alterations in mouse
      models of prostate cancer.

PMID- 16425199
TI  - Solid-state NMR spectroscopy of the quadrupolar halogens: chlorine-35/37, bromine
      79/81, and iodine-127.
AB  - A thorough review of 35/37Cl, 79/81Br, and 127I solid-state nuclear magnetic
      resonance (SSNMR) data is presented. Isotropic chemical shifts (CS), quadrupolar
      coupling constants, and other available information on the magnitude and
      orientation of the CS and electric field gradient (EFG) tensors for chlorine,
      bromine, and iodine in diverse chemical compounds is tabulated on the basis of
      over 200 references. Our coverage is through July 2005. Special emphasis is
      placed on the information available from the study of powdered diamagnetic solids
      in high magnetic fields. Our survey indicates a recent notable increase in the
      number of applications of solid-state quadrupolar halogen NMR, particularly 35Cl
      NMR, as high magnetic fields have become more widely available to solid-state NMR
      spectroscopists. We conclude with an assessment of possible future directions for
      research involving 35/37Cl, 79/81Br, and 127I solid-state NMR spectroscopy.

PMID- 16425200
TI  - Regulation of urogenital smooth muscle patterning by testosterone and estrogen
      during prostatic induction.
AB  - BACKGROUND: Smooth muscle (SM) has been proposed to play an important role in
      controlling prostate organogenesis by regulating signaling between inductive
      mesenchyme and developing epithelial prostatic buds. METHODS: We have examined
      the effects of testosterone and estrogen upon SM patterning in the embryonic rat
      urogenital tract (UGT) using in vitro organ cultures, immunohistochemistry, and
      Western blotting. RESULTS: We observed that testosterone elicited a sexually
      dimorphic difference in SM structure of embryonic UGTs, in cultures grown with
      testosterone. The addition of estrogen led to an increase in the rate of SM
      closure, in both males and females. To quantify the effects of steroids upon SM
      we used Western blotting of SM actin, which showed that estrogen stimulated SM
      content, while testosterone reduced SM content. Finally, we examined the
      expression of ERalpha, ERbeta, PR, and SM actin under different hormonal
      treatments of UGTs grown in vitro. The expression patterns of ERalpha and ERbeta
      were largely unchanged by hormonal treatment, while PR showed a much broader
      expression pattern in response to estradiol. CONCLUSIONS: Our results indicate
      that testosterone can directly regulate SM patterning and content in the UGT, and
      that SM is sensitive to both androgens and estrogens.

PMID- 16425201
TI  - Regulation of prostate 5alpha-reductase-2 gene expression and prostate weight by
      dietary fat and caloric intake in the rat.
AB  - BACKGROUND: High-fat diet is a major risk factor for prostate cancer. 5alpha
      reductases are potential targets of dietary fat. METHODS: Male ACI/Seg rats given
      either a low-fat or a high-fat diet at weaning or adulthood were sacrificed at 2,
      4, and 10 weeks after dietary treatment. Prostate 5alpha-reductase mRNAs, plasma
      androgens, food consumption, prostate, and body weight were determined. RESULTS:
      Prostate 5alpha-reductase-2 mRNA and plasma dihydrotestosterone levels were
      elevated at 2 weeks, and prostate weight was increased at 10 weeks in neonatal
      rats fed the high-fat diet. Animals fed the high-fat diet consumed more calories
      in the first 4 weeks. 5alpha-reductase-1 mRNA, plasma testosterone, and body
      weight were not different between the two dietary groups. These dietary effects
      were not observed in adult rats fed the same diets. CONCLUSION: A high-dietary
      fat and caloric intake upregulates prostate 5alpha-reductase-2 gene expression,
      and stimulates prostate growth in neonatal, but not adult rats.

PMID- 16425202
TI  - Overexpression of ecto-protein kinases in prostasomes of metastatic cell origin.
AB  - BACKGROUND: Prostasomes are secretory granules produced, stored, and released by
      the glandular epithelial cells of the prostate. They express numerous enzymes
      whose physiological roles have so far not been fully evaluated. In this study, we
      investigated the expression and function of prostasomal protein kinases and
      ATPase. METHODS: The protein kinase activities of prostasomes isolated from
      seminal fluid and malignant prostate cell lines (PC-3, DU145, and LNCaP) were
      investigated using the model phosphorylation substrates histone and casein, as
      well as the plasma proteins C3 and fibrinogen, in combination with specific
      protein kinase inhibitors. The prostasomal ATPase activity was also evaluated.
      The expression of protein kinases and ATPase on prostasomes was verified by flow
      cytometry. RESULTS: Prostasomes (intact or solubilized with octylglucoside or
      saponin) from prostate cancer cells had higher expression of protein kinases A,
      C, and casein kinase II compared to prostasomes isolated from seminal plasma,
      resulting in higher phosphorylation of both exogenous and endogenous substrates.
      Using intact prostasomes, it was found that prostasomes of metastatic origin had
      lower ATPase activity, resulting in higher residual ATP available for the
      phosphorylation reaction. Finally, complement component C3 and fibrinogen (two
      proteins whose activities are modulated by phosphorylation) were identified as
      physiologically relevant phosphorylation substrates. CONCLUSIONS: These results
      indicate that prostasomes are capable of modifying proteins possibly involved in
      the innate response by extracellular phosphorylation mediated by ecto-kinases.
      This is a novel mechanism by which prostatic malignant cells may interact with
      their environment.

PMID- 16425204
TI  - Abstracts of the First World Parkinson Congress, February 22-26, 2006,
      Washington, DC, USA.

PMID- 16425203
TI  - Methylation of the ASC gene promoter is associated with aggressive prostate
      cancer.
AB  - BACKGROUND: The aim of this study was to investigate the methylation status of
      apoptosis-associated speck-like protein containing a CARD (ASC; TMS1; PYCARD) in
      prostate cancer cell lines and human tissues and to determine if those findings
      correlate with the clinicopathological features of prostate cancer. METHODS:
      Genomic DNA was isolated from prostate cell lines and microdissected tissues,
      bisulfite converted and analyzed by methylation specific polymerase chain
      reaction (MSP). Expression of ASC in prostate cancer cell lines treated with or
      without methylation inhibitors was determined by quantitative or qualitative RT
      PCR. RESULTS: ASC gene expression was silenced or reduced in five prostate cancer
      cell lines and correlated with methylation status. Treatment of MDAPCa2b prostate
      cancer cells with the methylation inhibitors 5-aza-2-deoxycitidine and Zebularine
      reactivated expression of ASC. Of 58 prostate cancer specimens, methylation of
      the ASC promoter region was present in 65% of primary cancer tissue, 64% (7/11)
      of cancer-associated high grade-prostatic intraepithelial neoplasia (HG-PIN), and
      28% of normal-appearing but adjacent to tumor prostate tissue. While ASC
      methylation was not related to Gleason score (P = 0.46) or pathological stage (P
      = 0.75), there was a significantly higher frequency of ASC methylation in the
      adjacent normal tissue for patients with biochemical recurrence (P = 0.0383).
      CONCLUSIONS: Methylation of the ASC gene promoter is both a frequent and early
      event in prostate cancer carcinogenesis. Surprisingly, methylation of the
      adjacent normal tissue occurs significantly more often in patients who later
      undergo biochemical recurrence, suggesting a role for inactivation of the ASC
      gene in the initial stages of aggressive disease.

PMID- 16425209
TI  - Multiplicity-edited broadband HMBC NMR spectra.
AB  - A new, edited HMBC experiment is introduced that leads to two subspectra
      according to the number of protons attached to 13C nuclei being even or odd, i.e.
      one subspectrum with C + CH2 and another with CH + CH3. This experiment can be
      useful for resolving spectral overlap among the typically large number of peaks
      in HMBC spectra. It is implemented in a broadband version similar to broadband
      HMBC and demonstrated on prednisolone [(11beta)-11,17,21-trihydroxypregna-1,4
      diene-3,20-dione].

PMID- 16425210
TI  - Comments on 'Piperidone derivative from Dalbergia sympathetica'.
AB  - Alcoholic extraction of Dalbergia sympathetica leaves yielded N-methyl-trans-4
      hydroxy-L-proline and not 3,6-dihydroxy-N-methyl-2-piperidone, as previously
      reported. This is shown by the identity of the 1H and 13C NMR data of the
      isolated compound with those of N-methyl-trans-4-hydroxy-L-proline.

PMID- 16425211
TI  - Effects of imatinib mesylate (Glivec) as a c-kit tyrosine kinase inhibitor in the
      guinea-pig urinary bladder.
AB  - AIMS: In the gastrointestinal tract, slow wave activity in smooth muscle is
      generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips
      of most species show spontaneous contractions which are triggered by action
      potential bursts, however, the pacemaker mechanisms for the detrusor are still
      unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using
      antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c
      kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig
      detrusor and intravesical pressure of isolated guinea-pig bladders. METHODS:
      Changes in the membrane potential were measured in guinea-pig detrusor smooth
      muscle using conventional microelectrode techniques. Pressure changes in the
      bladder were recorded using whole organ bath techniques. RESULTS: Smooth muscle
      cells in detrusor muscle bundles exhibited spontaneous action potentials, and
      spontaneous pressure rises occurred in isolated bladders. Glivec (10 microM)
      converted action potential bursts into continuous firing with no effects on the
      shape of individual action potentials. Glivec (>50 microM) reduced the amplitude
      of spontaneous pressure rises in the whole bladder in a dose dependent manner and
      abolished spontaneous action potentials in detrusor smooth muscle cells.
      CONCLUSIONS: The results suggest that ICC-like cells may be responsible for
      generating bursts of action potentials and contractions in detrusor smooth
      muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the
      overactive bladder.

PMID- 16425212
TI  - Meta-analysis of association of rare mutations and common sequence variants in
      the MSR1 gene and prostate cancer risk.
AB  - BACKGROUND: MSR1 has been reported to be associated with increased risk of
      prostate cancer (PCa). METHODS: We performed a meta-analysis of all eight
      published studies to evaluate the pooled effect of three rare mutations (R293X,
      S41T, and D174Y) and five common sequence variants (PRO3, INDEL1, IVS5-59, P275A,
      and INDEL7), stratified by race and sporadic/hereditary cancer. RESULTS: Several
      variants were significantly or marginally significantly associated with sporadic,
      not hereditary PCa risk, including R293X in white men (random effect OR = 1.34, P
      = 0.09) and D174Y in black men (random effect OR = 2.41, P = 0.04). The
      associations were not significant when the initial study was excluded. However,
      the frequency of the D174Y mutation was consistently higher among cases in all
      three studies that examined black men. CONCLUSIONS: Overall, this meta-analysis
      suggests the MSR1 gene does not independently confer a major risk to PCa but may
      confer a moderate risk to PCa, especially in black men.

PMID- 16425213
TI  - 1H and 13C NMR data for indolo[2,3-b]quinoline-aminoglycoside hybrids, a novel
      potent anticancer drug family.
AB  - The complete NMR signal assignment of title compounds were carried out by
      extensive use of 1D and 2D NMR techniques (1H, 13C, GCOSY, GHSQC and GHMBC).

PMID- 16425214
TI  - 1H and 13C spectral assignment of 4-aryl-1,4,5,6,7,8-hexahydro-2,7,7,5-oxo
      quinolines 3-substituted derivatives.
AB  - The 1H and 13C NMR spectroscopic data for 4-aryl-1,4,5,6,7,8-hexahydro-2,7,7,5
      oxo-quinoline 3-substituted derivatives have been fully assigned by the
      combination of one- and two dimensional experiments (DEPT, HMBC, HMQC, COSY,
      NOE).

PMID- 16425216
TI  - Pax6-induced alteration of cell fate: shape changes, expression of neuronal alpha
      tubulin, postmitotic phenotype, and cell migration.
AB  - The transcription factor Pax6 plays an important role in the development of the
      central nervous system. To understand its mechanism of action, we transduced HeLa
      cells with a Pax6-expressing lentiviral vector. Upon transduction, HeLa cells
      markedly changed shape and formed neuritelike extensions. Pax6-transduced HeLa
      cells expressed high levels of neuronal alpha3 tubulin, demonstrating a partial
      transdifferentiation towards a neuronal phenotype. Neurons are postmitotic cells.
      Pax6-transduced HeLa cells became postmitotic through mechanisms involving up
      regulation of p53 and cyclin-dependent kinase inhibitor p21. One of the most
      striking effects of Pax6 was observed by time-lapse videomicroscopy: cells
      started to dissociate from cell clusters and displayed intense migratory
      activity. Migration was accompanied by dynamic and reversible shape changes. Our
      results identified three elements of Pax6 action: (i) expression of neuron
      specific genes; (ii) establishment of a postmitotic phenotype; and (iii)
      involvement in the regulation of cell shape and cell migration.

PMID- 16425218
TI  - BMP and FGF-2 regulate neurogenin-2 expression and the differentiation of sensory
      neurons and glia.
AB  - We have examined the effects of signaling molecules and Notch signaling on the
      mechanisms regulating neurogenin (ngn)-2 expression. This ngn-2 is a
      transcription factor that is essential for the specification of early
      differentiating sensory neurons in the dorsal root ganglia. In the presence of
      bone morphogenetic protein (BMP), anti-ngn-2-positive cells appeared in mouse
      trunk neural crest cell cultures, and they expressed Brn3, indicating that ngn-2
      expressing cells are sensory neurons. These cells did not differentiate after
      fibroblast growth factor (FGF)-2 treatment or after Notch activation. The
      suppression of ngn-2 expression by FGF-2 was recovered by treatment with a Notch
      signaling inhibitor. Thus, FGF-2 may prevent ngn-2 expression through Notch
      activation. Whereas BMP-4 inhibited glial differentiation, FGF-2 promoted
      gliogenesis by means of Notch activation. Our data suggest that BMP and FGF-2 act
      as positive and negative regulators in ngn-2 expression, respectively, and that
      these signaling molecules regulate the differentiation of sensory neurons and
      glia.

PMID- 16425215
TI  - Asymmetric localization of numb in the chick somite and the influence of myogenic
      signals.
AB  - Whereas Notch signaling is known to play an essential role in the formation of
      somites, its role during later stages of somite maturation is less well
      understood. Here, we examine the signals and transcription factors that control
      the expression of the Notch antagonist, Numb, during somite maturation in the
      chick embryo. Numb mRNA is present in the epithelial somite and is increased in
      expression in the forming myotome. Numb protein displays a very specific
      subcellular localization and dynamic expression during somite maturation. Numb
      protein is asymmetrically localized in a cortical crescent on the basal side of
      dividing cells in the dorsomedial lip of the dermomyotome and is subsequently
      uniformly distributed throughout differentiated myotomal cells. Treatment of
      somites with either the combination of Wnt-3a and Shh, or ectodermal signals plus
      noggin, both of which induce somitic myogenesis, did not significantly affect
      Numb transcript levels but did lead to a dramatic increase in the levels of Numb
      protein, which was uniformly distributed throughout the cytoplasm of the
      resultant myotubes. Forced expression of MyoD in somites similarly induced high
      levels of Numb protein throughout the cytoplasm, without affecting Numb mRNA
      levels. We also found that signals that promote somitic myogenesis or forced MyoD
      expression induced expression of the Notch ligand, Serrate-2. Our findings
      suggest that Notch signals are specifically repressed in the myotome and that
      asymmetric expression of Numb in dividing cells of the dorsomedial lip of the
      dermomyotome may modulate whether these cells continue to divide or differentiate
      into myotomal cells.

PMID- 16425217
TI  - Why is delta endocytosis required for effective activation of notch?
AB  - A number of recent studies have shown that endocytosis of Notch ligands is
      required for activation of Notch. There are at least two broad models that
      account for how Delta endocytosis in one cell might contribute to activation of
      Notch in the neighboring cell. The first class of models is related to the
      possibility that Delta endocytosis facilitates S2 cleavage and removal of the
      Notch extracellular domain, a critical step in Notch activation. A second class
      of models is related to the possibility that Delta ubiquitylation and endocytosis
      facilitates interactions between Delta and Notch. In the second set of models,
      Delta undergoes endocytosis and its subsequent trafficking back to the surface,
      following modifications or some change in the context in which it is presented,
      makes Delta a more effective ligand. Though it is still not clear how either or
      both mechanisms contribute, recent evidence points to the importance of both
      endocytosis and recycling in Delta signaling.

PMID- 16425219
TI  - Myostatin imposes reversible quiescence on embryonic muscle precursors.
AB  - We have previously shown that Myostatin, a member of the transforming growth
      factor beta (TFG-beta) family of signalling molecules, is expressed in developing
      muscle, and that treatment with recombinant Myostatin inhibited the expression of
      key myogenic transcription factors during chick embryogenesis. In this study, we
      followed the fate of muscle precursors after exposure to Myostatin. We report
      that in contrast to the down-regulation in expression of Pax-3, Myf-5, MyoD, and
      Myogenin, expression of Pax-7 was maintained. However, Myostatin completely
      inhibited cell division in the Pax-7-expressing cells. The inhibitory effect of
      Myostatin was reversible, as upon withdrawal myogenic cells re-initiated cell
      proliferation as well as expression of Pax-3 and MyoD. These results led us to
      investigate the temporal and spatial distribution of quiescent muscle precursors
      during development. To this end, we analysed distribution and mitotic behaviour
      of Pax-7-expressing cells during muscle development. Our studies revealed two
      populations of Pax-7-expressing cells, one that proliferated and incorporated
      BrdU, whilst the other did not. At early developmental stages, a high proportion
      of Pax-7-expressing cells proliferated, but there was a significant number of non
      dividing Pax-7-expressing cells intermingled with differentiated muscle.
      Proliferating precursors became less frequent as development proceeded and at
      late fetal stages all Pax-7-expressing cells were mitotically quiescent. We
      suggest that Myostatin is an important signalling molecule responsible for
      imposing quiescence upon myogenic precursors during embryonic and foetal
      development.

PMID- 16425221
TI  - Reorganization of cytoplasm in the zebrafish oocyte and egg during early steps of
      ooplasmic segregation.
AB  - The aim of this work is to determine when and how ooplasmic segregation is
      initiated in the zebrafish egg. To this end, the organization of the ooplasm and
      vitelloplasm were examined in oocytes and eggs shortly after activation.
      Ooplasmic segregation, initiated in the stage V oocyte, led to the formation of
      ooplasmic domains rich in organelles, and ribonucleoproteins. A linear array of
      closely arranged peripheral yolk globules separated an outer domain of ectoplasm
      from an inner domain of interconnected endoplasmic lacunae. The structure of this
      yolk array and the distribution of microinjected labeled tracers suggests that it
      may provide a barrier limiting ooplasm transit. Loosely arranged yolk globules at
      the animal hemisphere allow wide connections between the endoplasm and a
      preblastodisc domain. Activation caused further segregation of ooplasm,
      reorganization of endoplasmic lacunae, and blastodisc growth. The presence of an
      endoplasmic cytoskeleton suggests that these changes may be driven by
      microtubules and microfilaments.

PMID- 16425222
TI  - Joint formation in the middle ear: lessons from the mouse and guinea pig.
AB  - The malleus, incus and stapes form an ossicle chain in the mammalian middle ear.
      These ossicles are articulated by joints that link the chain together. In humans
      and mice, fusion of the ossicles leads to hearing loss. However, in the adult
      guinea pig the malleus and incus are normally found as a single complex. In this
      report, we investigate how the malleus and incus form during mouse and guinea pig
      development. The murine malleus and incus develop from a single condensation that
      splits to form the two ossicles. Even before a morphological split, we show that
      the ossicles have distinct genetic identities and joint markers are expressed. In
      the guinea pig embryo, joint formation is initiated but no cavitation is
      observed, resulting in a single complex divided by a thin suture. The malleal
      incudo complex in the guinea pig is, therefore, not caused by a defect in joint
      initiation.

PMID- 16425223
TI  - Assessing the likelihood of severe side effects in radiotherapy.
AB  - Ionizing radiation is a powerful tool to treat cancer. The curing effect is
      mainly based on the efficiency of ionizing radiation to kill the cancer cells and
      it is believed that DNA double-strand breaks (DSBs) represent the most
      significant genetic lesion introduced by radiation that causes cell killing. One
      limitation in radiotherapy is the unavoidable damage delivered to the normal,
      noncancer cells that can give rise to side effects. The ultimate goal in
      treatment planning is to maximize cell killing in the tumor by minimizing damage
      induction in the normal tissue surrounding the tumor. The biological response to
      the induction of DSBs is largely affected by DSB repair processes and it has,
      therefore, been a long-standing goal to determine a patient's DSB repair capacity
      to "individualize" treatment planning. A recently developed DSB repair assay that
      allows the assessment of patients' repair capacity under in vivo conditions may
      provide a new approach to predict individuals' responses to radiotherapy and may
      be able to contribute to improvements in treatment planning.

PMID- 16425220
TI  - Differential inhibition of Wnt-3a by Sfrp-1, Sfrp-2, and Sfrp-3.
AB  - Secreted frizzled related proteins (Sfrps) are extracellular attenuators of Wnt
      signaling that play important roles in both embryogenesis and oncogenesis.
      Although Sfrps are generally thought to bind and sequester Wnts away from active
      receptor complexes, very little is known about the specificity of Sfrp family
      members for various Wnts. In the developing chick neural tube, sfrp-1, 2, and 3
      transcripts are expressed in and adjacent to the dorsal neural tube, where Wnt-1
      and Wnt-3a are expressed. To better define the possible roles of Sfrp-1, 2, and 3
      in the neural tube, we first tested the ability of purified Sfrps to inhibit Wnt
      3a-induced accumulation of beta-catenin in L cells. We find that both Sfrp-1 and
      Sfrp-2 can inhibit Wnt-3a activity while Sfrp-3 cannot. To determine where Sfrp-1
      and Sfrp-2 impinge on the Wnt signaling pathway, we tested the ability of these
      Sfrps to inhibit Wnt signaling induced by the addition of LiCl, an inhibitor of
      GSK-3. Sfrp-1 and Sfrp-2 are unable to inhibit the accumulation of beta-catenin
      in LiCl-treated cells, suggesting that the ability of Sfrps to inhibit the
      accumulation of beta-catenin is GSK-3 dependent. We have further shown that Sfrp
      2 inhibits the ability of ectopic Wnt-3a to stimulate proliferation in the
      developing chick neural tube. These results provide the framework for
      understanding how Sfrps function to regulate Wnt-3a activity in developing
      embryos and in cancer.

PMID- 16425224
TI  - HSP70 vaccine in combination with gene therapy with plasmid DNA encoding sPD-1
      overcomes immune resistance and suppresses the progression of pulmonary
      metastatic melanoma.
AB  - Many tumor immunotherapy efforts are focused on the generation of strong T-cell
      response against tumor antigens. However, strong T-cell response does not always
      coincide with tumor rejection, for which upregulated expression of
      immunoinhibitory molecules may be responsible. In this study, the treatment with
      heat shock protein 70 (HSP70) vaccine induced an infiltration of T cells into the
      tumor site as well as the expression of IFN-gamma and IL-2, and delayed lung
      metastases of tumor, but the tumor progression nonetheless occur finally. We
      demonstrated that B7-H1 expressed by residual tumor cells was responsible for the
      resistance of tumor to the therapy with HSP70 vaccine. Blockade of B7-H1 by i.v.
      injection pPD-1A, a plasmid encoding the extracellular domain of PD-1 (sPD-1),
      could reverse this resistance and enhance the therapeutic efficacy. To complement
      these findings, we investigated the gene expression of tumor-infiltrating
      lymphocytes (TILs) by Real-time PCR analysis, which revealed that the expression
      of TH1 cytokines IFN-gamma and IL-2 by TIL in the mice treated with HSP70 vaccine
      in combination with sPD-1 was increased and the expression of negative regulatory
      molecules IL-10, TGF-beta and foxp3 was decreased, demonstrating that
      multifunctional properties afforded by the combination therapy can effectively
      overcome tumor resistance and promote effective antitumor immunity. The in vivo
      transfection with pPD-1A could be performed as infrequently as once a week and
      still produce a significant antitumor effect. These findings suggest that the
      treatment with HSP70 vaccine followed by blockade of tumor-B7-H1 with sPD-1 may
      provide a promising approach for tumor immunotherapy.

PMID- 16425225
TI  - Increased PTEN expression due to transcriptional activation of PPARgamma by
      Lovastatin and Rosiglitazone.
AB  - Germline mutations in the tumor suppressor gene PTEN (protein phosphatase and
      tensin homolog located on chromosome ten) predispose to heritable breast cancer.
      The transcription factor PPARgamma has also been implicated as a tumor suppressor
      pertinent to a range of neoplasias, including breast cancer. A putative PPARgamma
      binding site in the PTEN promoter indicates that PPARgamma may regulate PTEN
      expression. We show here that the PPARgamma agonist Rosiglitazone, along with
      Lovastatin, induce PTEN in a dose- and time-dependent manner. Lovastatin- or
      Rosiglitazone-induced PTEN expression was accompanied by a decrease in
      phosphorylated-AKT and phosphorylated-MAPK and an increase in G1 arrest. We
      demonstrate that the mechanism of Lovastatin- and Rosiglitazone-associated PTEN
      expression was a result of an increase in PTEN mRNA, suggesting that this
      increase was transcriptionally-mediated. Compound-66, an inactive form of
      Rosiglitazone, which is incapable of activating PPARgamma, was unable to elicit
      the same response as Rosiglitazone, signifying that the Rosiglitazone response is
      PPARgamma-mediated. To support this, we show, using reporter assays including
      dominant-negative constructs of PPARgamma, that both Lovastatin and Rosiglitazone
      specifically mediate PPARgamma activation. Additionally, we demonstrated that
      cells lacking PTEN or PPARgamma were unable to induce PTEN mediated cellular
      events in the presence of Lovastatin or Rosiglitazone. These data are the first
      to demonstrate that Lovastatin can signal through PPARgamma and directly
      demonstrate that PPARgamma can upregulate PTEN at the transcriptional level.
      Since PTEN is constitutively active, our data indicates it may be worthwhile to
      examine Rosiglitazone and Lovastatin stimulation as mechanisms to increase PTEN
      expression for therapeutic and preventative strategies including cancer, diabetes
      mellitus and cardiovascular disease.

PMID- 16425226
TI  - Differential regulation of GDF-5 and FGF-2/4 by immobilisation in ovo exposes
      distinct roles in joint formation.
AB  - Members of the fibroblast growth factor (FGF) family and growth and
      differentiation factor 5 (GDF-5) have been implicated in joint specification, but
      their roles in subsequent cavity formation are not defined. Cavity formation
      (cavitation) depends upon limb movement in embryonic chicks and factors involved
      in joint formation are often identified by their expression at the joint-line. We
      have sought support for the roles of FGF-2, FGF-4, and GDF-5 in cavitation by
      defining expression patterns, immunohistochemically, during joint formation and
      establishing whether these are modified by in ovo immobilisation. We found that
      FGF-2 exhibited low level nuclear expression in chondrocytes and fibrocartilage
      cells close to presumptive joints, but showed significantly higher expression
      levels in cells at, and directly bordering, the forming joint cavity. This high
      level joint line FGF-2 expression was selectively diminished in immobilised
      limbs. In contrast, we show that FGF-4 does not exhibit differential joint-line
      expression and was unaffected by immobilisation. GDF-5 protein also failed to
      show joint-line selective labelling, and although immobilisation induced a
      cartilaginous fusion across presumptive joints, it did not affect cellular GDF-5
      expression patterns. Examining changes in GDF-5 expression in response to a
      direct mechanical strain stimulus in primary embryonic chick articular surface
      (AS) cells in vitro discloses only small mechanically-induced reductions in GDF-5
      expression, suggesting that GDF-5 does not exert a direct positive contribution
      to the mechano-dependent joint cavitation process. This notion was supported by
      retroviral overexpression of UDPGD, a characteristic factor involved in
      hyaluronan (HA) accumulation at presumptive joint lines, which was also found to
      produce small decreases in AS cell GDF-5 expression. These findings support a
      direct mechano-dependent role for FGF-2, but not FGF-4, in the cavitation process
      and indicate that GDF-5 is likely to influence chondrogenesis positively without
      contributing directly to joint cavity formation.

PMID- 16425227
TI  - The role of N-methyl-D-asparate receptors in neurogenesis.
AB  - The dentate gyrus continues to incorporate granule neurons during adulthood.
      Among the factors that we know modulate adult neurogenesis in the dentate gyrus,
      one of the first studied was the influence of excitatory amino-acids. These
      neurotransmitters, acting through NMDA receptors, are able to modulate both the
      proliferation of progenitor cells as well as the rate of neurogenesis in the
      adult dentate gyrus. However, the mechanisms by which these processes are
      influenced are not clearly known. Although there is no anatomical evidence of
      NMDA receptor expression in adult hippocampal progenitor cells or differentiating
      granule neurons, electrophysiological data and in vitro studies suggest that NMDA
      receptors may be expressed by certain precursor cells and immature granule
      neurons. This review summarizes findings on the influence of pharmacological
      manipulation of NMDA receptors on adult neurogenesis. We also analyze previous
      studies that have suggested the expression of NMDA receptors in progenitors and
      immature granule cells and discuss the putative role of these receptors in the
      regulation of developmental processes such as proliferation, migration, or
      neurite outgrowth.

PMID- 16425228
TI  - Expression of p27BBP/eIF6 is highly modulated during Xenopus laevis
      embryogenesis.
AB  - Protein p27BBP/eIF6 is necessary for ribosomal function of all cells. Previous
      data showed that from mammals to yeast p27BBP/eIF6 is involved in the biogenesis
      of ribosomal subunit 60S and its association with the 60S prevents premature 80S
      formation regulated by PKC signaling, indicating that phosphorylation of
      p27BBP/eIF6 is needed for translation to occur. While in vitro p27BBP/eIF6 is
      constitutively expressed, and it has a high level of expression in cycling cells,
      in vivo its expression varies according to tissues and appears regulated by
      factors up to now unknown. p27BBP/eIF6 has never been investigated in developing
      organisms where its upregulation can be correlated with tissue growth and
      differentiation. In this study we have sequenced p27BBP/eIF6 cDNA and studied its
      expression during development of Xenopus laevis, as the first step for studying
      its regulation. The amino acid sequence is highly conserved with two putative PKC
      phosphorylation sites in serine, one site being typical of Xenopus. At the end of
      gastrulation, the p27BBP/eIF6 riboprobe localizes in the neural plate and in the
      paraxial mesoderm. In particular, from stage 24, a clear-cut localization occurs
      in the perspective head. In embryos exposed to teratogens, the localization of
      p27BBP/eIF6 riboprobe varies according to the change of head size caused by the
      treatment. p27BBP/eIF6 expression is particularly evident in differentiating
      olfactory pits, the lens, otic vesicles, and in branchial arches. Features of
      particular interest are p27BBP/eIF6 high level of expression in the eye field,
      and in the mid-hindbrain-boundary, two regions with high proliferative activity.
      Altogether, data indicate that a modulated expression of p27BBP/eIF6 occurs in
      developing anlagens in addition to a basal level of expression, and may suggest a
      correlation between p27BBP/eIF6 and proliferative activity. Moreover, the X.
      laevis cDNA isolation and characterization offer new hints for further studies in
      relation to potential p27BBP/eIF6 phosphorylation.

PMID- 16425229
TI  - Denuding and centrifugation of maturing bovine oocytes alters oocyte spindle
      integrity and the ability of cytoplasm to support parthenogenetic and nuclear
      transfer embryo development.
AB  - The effects of cumulus cell removal and centrifugation of maturing bovine oocytes
      on nuclear maturation and subsequent embryo development after parthenogenetic
      activation and nuclear transfer were examined. Removal of cumulus cells at 4, 8,
      and 15 hr after in vitro maturation (IVM) or the centrifugation of denuded
      oocytes had no effect on maturation rates. Oocytes treated at 0 hr of IVM had a
      lower expulsion rate (50%) of the first polar body (PB1). The removal of cumulus
      cells and centrifugation affected the pattern of spindle microtubule distribution
      and division of chromosomes. There were almost no spindle microtubules allocated
      to PB1 and the spindles were swollen in anaphase I and telophase I oocytes.
      Approximately 20% of PB1 oocytes contained tripolar or multipolar spindles. After
      activation, oocytes denuded with or without centrifugation at 8 hr of IVM
      resulted in the lowest rate of development (3.0%). Denuded oocytes at 4, 15, and
      24 hr of IVM with centrifugation or not resulted in similar blastocyst
      development rates (9.6%-13.2%). However, centrifugation of oocytes denuded at the
      beginning of IVM resulted in lower blastocyst development rate (8.1%, P < 0.05)
      than the noncentrifuged oocytes (17.3%). After nuclear transfer, the blastocyst
      development rates of oocytes denuded and centrifuged at 0, 4, and 8 hr of IVM
      were not different when compared to the same patch of noncentrifuged oocytes.
      However, oocytes denuded and centrifuged at 15 hr of IVM resulted in lower (P <
      0.05) blastocyst development rates than the noncentrifuged oocytes. The results
      of this study suggest that removal of cumulus cells and centrifugation of denuded
      oocytes affect the spindle pattern. Embryo development of denuded and centrifuged
      oocytes may differ depending on the time of removal of cumulus cells.

PMID- 16425230
TI  - Chimeric honeybees (Apis mellifera) produced by transplantation of embryonic
      cells into pre-gastrula stage embryos and detection of chimerism by use of
      microsatellite markers.
AB  - The production of chimeras, by use of cell transplantation, has proved to be
      highly valuable in studies of development by providing insights into cell fate,
      differentiation, and developmental potential. So far, chimeric honeybees have
      been created by nuclear transfer technologies. We have developed protocols to
      produce chimeric honeybees by use of cell transplantation. Embryonic cells were
      transplanted between pre-gastrula stage embryos (32-34 hr after oviposition) and
      hatched larvae were reared in vitro for 4 days. Chimeric individuals were
      detected by use of microsatellite analysis and a conservative estimation
      approach. 4.8% of embryos, posteriorly injected with embryonic cells, developed
      into chimeric honeybee larvae. By injection of cells pre-stained with fluorescent
      cell tracer dye, we studied the integration of transplanted cells in the
      developing embryos. Number of injected cells varied from 0 to 50 and cells
      remained and multiplied mainly in the area of injection.

PMID- 16425231
TI  - Fine characterization of the Iceman's mtDNA haplogroup.
AB  - Starting from specimens of the intestinal contents of the so-called Tyrolean
      Iceman or Otzi (5,350-5,100 years before present), it was possible by polymerase
      chain reaction to amplify fragments of the human mitochondrial DNA (mtDNA)
      control region that correspond to the sequence found in 1994 at the Munich and
      Oxford laboratories and which had been attributed to the original DNA of the
      mummy. The particularly favorable condition of the specimens, showing very low
      contamination levels, made it easier to extend the analyses to the coding region,
      which had not previously been considered. The mtDNA of the European population is
      currently divided into nine (H, T, U, V, W, X, I, J, and K) main groups
      (haplogroups). The K haplogroup, in particular, is composed of two (K1 and K2)
      subclusters. The results demonstrate that the Iceman's mtDNA belongs to the K1
      subcluster, yet it does not fit any of the three known branches (a, b, and c)
      into which the K1 subcluster is presently divided. In addition, some other sites,
      reported to be linked to environmental adaptation or pathologies, were
      investigated.

PMID- 16425232
TI  - Variation in occlusal dental wear of two Chalcolithic populations in the southern
      Levant.
AB  - Occlusal wear rate and wear plane in two Chalcolithic ( approximately 6500-5500
      BP) samples from the southern Levant were compared, using paired first and second
      mandibular molars. Though food staples in both societies were derived from agro
      pastoralism, they were located in distinct environmental regions: Wadi (W.)
      Makkukh in the Judean desert, and Peqi'in in the Upper Galilee. Accordingly, it
      was predicted that variation in wear should occur due to their location in
      distinct environments. Jaw size and tooth size were measured to estimate the
      possible impact of these variables on wear scores. Molar occlusal surfaces were
      divided into four quadrants, and wear scores were recorded for each quadrant.
      Principal axis analysis was then performed between total wear scores of paired,
      adjacent first and second molars to assess wear rates. Principal axis analysis
      was also used to analyze the change in occlusal wear plane in each sample by
      comparing between-buccal-cusps wear scores of the first molar with lingual wear
      scores of the second molar. The results indicate that the occlusal wear plane was
      similar in both samples but that wear tended to be more rapid in W. Makkukh.
      Since both samples were similar in jaw/tooth size, it is argued that the results
      reflect less refined food-processing methods as well as the unintentional
      ingestion of sand by individuals interred in the Judean desert.

PMID- 16425233
TI  - Ca2+ and Na+ current patterns during oocyte maturation, fertilization, and early
      developmental stages of Ciona intestinalis.
AB  - Using the whole-cell voltage clamp technique, the electrical changes in oocyte
      and embryo plasma membrane were followed during different meiotic and
      developmental stages in Ciona intestinalis. We show, for the first time, an
      electrophysiological characterization of the plasma membrane in oocytes at the
      germinal vesicle (GV) stage with high L-type calcium (Ca2+) current activity that
      decreased through meiosis. Moreover, the absence of Ca2+ reduced germinal vesicle
      breakdown (GVBD), which is consistent with a role of Ca2+ currents in the
      prophase/metaphase transition. In mature oocytes at the metaphase I (MI) stage,
      Ca2+ currents decreased and then disappeared and sodium (Na+) currents first
      appeared remaining high up to the zygote stage. Intracellular Ca2+ release was
      higher in MI than in GV, indicating that Ca2+ currents in GV may contribute to
      fill the stores which are essential for oocyte contraction at fertilization. The
      fertilization current generated in Na+ free sea water was significantly lower
      than the control; furthermore, oocytes fertilized in the absence of Na+ showed
      high development of anomalous "rosette" embryos. Current amplitudes became
      negligible in embryos at the 2- and 4-cell stage, suggesting that signaling
      pathways that mediate first cleavage do not rely on ion current activities. At
      the 8-cell stage embryo, a resumption of Na+ current activity and conductance
      occurred, without a correlation with specific blastomeres. Taken together, these
      results imply: (i) an involvement of L-type Ca2+ currents in meiotic progression
      from the GV to MI stage; (ii) a role of Na+ currents during electrical events at
      fertilization and subsequent development; (iii) a major role of plasma membrane
      permeability and a minor function of specific currents during initial cell line
      segregation events.

PMID- 16425234
TI  - Genes associated with the formation of germ cells from embryonic stem cells in
      cultures containing different glucose concentrations.
AB  - In a previous study, we established a system for visualizing the development of
      germ cells from mouse embryonic stem (ES) cells in culture using knock-in ES
      clones in which visual reporter genes were expressed from the mouse vasa homolog,
      Mvh. While assessing various culture conditions, we found that germ-cell
      formation was markedly depressed in low glucose medium. Using a repeated
      polymerase chain reaction (PCR) subtraction method, we identified genes that were
      differentially expressed in low versus high glucose media. Three genes that were
      predominantly expressed in high glucose medium, thioredoxin-interacting protein
      (Txnip), pituitary tumor-transforming gene 1 (Pttg), and RuvB-like protein 2
      (RuvBl2), were further investigated. These genes were also found to be highly
      expressed in adult and embryonic gonads, and RuvBl2 in particular, which encodes
      an ATP-dependent DNA helicase, was specifically detected in the spermatocytes and
      spermatids of the adult testis as well as in primordial germ cells. Furthermore,
      using a green fluorescent protein (GFP) fusion construct, we found that RuvBl2
      was expressed in both the nucleus and cytoplasm of testicular germ cells. These
      findings suggest a possible relationship between glucose metabolism and germ-cell
      development.

PMID- 16425235
TI  - Establishment of an in vitro culture system for chicken preblastodermal cells.
AB  - To develop an alternative source for chicken pluripotent cells, we examined (1)
      whether undifferentiated preblastodermal cells could be subcultured in vitro for
      an extended period and (2) how subculturing affected the physiological properties
      of preblastodermal cells. The average number of preblastodermal cells was 2,397
      in stage V embryos and 36,345 in stage VII embryos; stage X embryos had an
      average of 53,857 blastodermal cells. The average cell size decreased
      significantly (70.63-18.83 microm in diameter; P < 0.0001) as the embryo grew;
      this was closely related to a reduction in the size and number of lipid vesicles
      in the cell cytoplasm. The culture conditions were optimized for the stage V
      preblastodermal cells and the control stage X blastodermal cells. On STO feeder
      cells, the preblastodermal cells achieved stable growth in vitro only in HES
      medium or a mixed medium of the Knockout DMEM and HES media. However, more than
      10 passages of preblastodermal cells at intervals of 3-4 days was possible only
      by using the Knockout/HES mixed medium and BRL cell-conditioned HES medium for
      the primary cultures and subcultures, respectively. Colony-forming
      preblastodermal cells had well-delineated cytoplasm, which was positively stained
      for stem cell-specific markers by anti-stage-specific embryo antigen-1 antibody,
      periodic acid-Schiff's solution, and alkaline phosphatase. When preblastodermal
      cells with or without culturing were transferred into the blastodermal cavity of
      stage X embryos, only in vitro-cultured preblastodermal cells at stage V (4/5 =
      80%) and stage VII (2/8 = 25%) induced somatic chimerism in recipient chickens.
      In conclusion, undifferentiated preblastodermal cells could be subcultured, and
      only the colony-forming preblastodermal cells that stained positively for stem
      cell markers could induce somatic chimerism.

PMID- 16425236
TI  - Hippocampal neurogenesis: opposing effects of stress and antidepressant
      treatment.
AB  - The hippocampus is one of several limbic brain structures implicated in the
      pathophysiology and treatment of mood disorders. Preclinical and clinical studies
      demonstrate that stress and depression lead to reductions of the total volume of
      this structure and atrophy and loss of neurons in the adult hippocampus. One of
      the cellular mechanisms that could account for alterations of hippocampal
      structure as well as function is the regulation of adult neurogenesis. Stress
      exerts a profound effect on neurogenesis, leading to a rapid and prolonged
      decrease in the rate of cell proliferation in the adult hippocampus. In contrast,
      chronic antidepressant treatment up-regulates hippocampal neurogenesis, and could
      thereby block or reverse the atrophy and damage caused by stress. Recent studies
      also demonstrate that neurogenesis is required for the actions of antidepressants
      in behavioral models of depression. This review discusses the literature that has
      lead to a neurogenic hypothesis of depression and antidepressant action, as well
      as the molecular and cellular mechanisms that underlie the regulation of adult
      neurogenesis by stress and antidepressant treatment.

PMID- 16425238
TI  - The matricellular protein SPARC is internalized in Sertoli, Leydig, and germ
      cells during testis differentiation.
AB  - The gene encoding the matricellular protein secreted protein, acidic and rich in
      cysteine (SPARC) was identified in a screen for genes expressed sex-specifically
      during mouse gonad development, as being strongly upregulated in the male gonad
      from very early in testis development. We present here a detailed analysis of
      SPARC gene and protein expression during testis development, from 11.5 to 15.5
      days post coitum (dpc). Section in situ hybridization analysis revealed that
      SPARC mRNA is expressed by the Sertoli cells in the testis cords and the fetal
      Leydig cells, found within the interstitial space between the testis cords.
      Immunodetection with anti-SPARC antibody showed that the protein was located
      inside the testis cords, within the cytoplasm of Sertoli and germ cells. In the
      interstitium, SPARC was present intracellularly within the Leydig cells. The
      internalization of SPARC in Sertoli, Leydig, and germ cells suggests that it
      plays an intracellular regulatory role in these cell types during fetal testis
      development.

PMID- 16425237
TI  - Hippocampal cell proliferation is reduced following prenatal ethanol exposure but
      can be rescued with voluntary exercise.
AB  - The ingestion of ethanol during pregnancy has a number of deleterious
      consequences for the unborn offspring, producing structural and functional
      deficits that affect the brain and many other organs into adulthood. The
      hippocampus is a brain area that is particularly sensitive to ethanol's adverse
      effects. In a previous study we showed that voluntary exercise can ameliorate
      deficits in long-term potentiation and behavior that occur following prenatal
      ethanol exposure (Eur J Neurosci, 2005, 21, 1719-1726). In the present study, we
      investigated the effects of prenatal ethanol exposure on neurogenesis in
      adulthood, and tested the hypothesis that voluntary exercise would ameliorate any
      deficits observed. Sprague-Dawley females were administered one of three diets
      throughout gestation: (i) ethanol (E), a liquid diet containing 36.5% ethanol
      derived calories; (ii) pair-fed (PF), a liquid control diet, with maltose-dextrin
      isocalorically substituted for ethanol, in the amount consumed by an E partner
      (g/kg body wt/day of gestation); and (iii) ad-libitum-fed control (C), normal
      laboratory chow and water, ad libitum. The offspring were housed individually at
      postnatal day (PND) 35, and at PND 50 were randomly assigned to cages either with
      or without an exercise wheel. BrdU (200 mg/kg, I.P.) was injected on PND 57, and
      animals terminated either 24 h (proliferation) or 4 weeks (neurogenesis) later.
      Our results demonstrate that prenatal ethanol exposure significantly decreases
      both cell proliferation and neurogenesis in the adult dentate gyrus. Animals in
      the PF condition also showed reduced neurogenesis. In contrast, all animals that
      engaged in voluntary exercise showed a significant increase in cell proliferation
      and neurogenesis. These results indicate that prenatal ethanol exposure can
      suppress both cell proliferation and neurogenesis, and that these effects may be,
      at least in part, nutritionally mediated. Importantly, voluntary exercise appears
      to have beneficial effects for these long-lasting deficits in hippocampal volume
      and cell number that have been observed in animals exposed to ethanol in utero.

PMID- 16425239
TI  - Comparing atomistic simulation data with the NMR experiment: how much can NOEs
      actually tell us?
AB  - Simulated molecular dynamics trajectories of proteins and nucleic acids are often
      compared with nuclear magnetic resonance (NMR) data for the purposes of assessing
      the quality of the force field used or, equally important, trying to interpret
      ambiguous experimental data. In particular, nuclear Overhauser enhancement (NOE)
      intensities or atom-atom distances derived from them are frequently calculated
      from the simulated ensembles because the distance restraints derived from NOEs
      are the key ingredient in NMR-based protein structure determination. In this
      study, we ask how diverse and nonnative-like an ensemble of structures can be and
      still match the experimental NOE distance upper bounds well. We present two
      examples in which simulated ensembles of highly nonnative polypeptide structures
      (an unfolded state ensemble of the villin headpiece and a high-temperature
      denatured ensemble of lysozyme) are shown to match fairly well the experimental
      NOE distance upper bounds from which the corresponding native structures were
      derived. For example, the unfolded ensemble of villin headpiece, which is on
      average 0.90 +/- 0.13 nm root-mean-square deviation away from the native NMR
      structure, deviates from the experimental restraints by only 0.027 nm on average.
      However, this artificially good agreement is largely a consequence of 1) the
      highly nonlinear effects of r(-6) (or r(-3)) averaging and 2) focusing only on
      the experimentally observed set of NOE bounds. Namely, in addition to the
      experimentally observed NOEs, both simulated ensembles (especially the villin
      ensemble) also predict a large number of NOEs, which are not seen in the
      experiment. If these are taken into account, the agreement between simulation and
      experiment gets markedly worse, as it should, given the nonnative nature of the
      underlying simulated ensembles. In light of the examples given, we conclude that
      comparing experimental NOE distance restraints with large simulated ensembles
      provides just by itself only limited information about the quality of simulation.

PMID- 16425240
TI  - Biodegradable polymeric microspheres and nanospheres for drug delivery in the
      peritoneum.
AB  - Drug delivery to the peritoneum is hampered by rapid clearance, and could be
      improved by application of controlled release technology. We investigated the
      suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co
      glycolic) acid (PLGA), a biodegradable polymer with generally excellent
      biocompatibility commonly used for controlled drug release. We injected 90 kDa
      PLGA microparticles, 5-250 microm in diameter, into the murine peritoneum, in
      dosages of 10-100 mg (n=3-5 per group). We found a high incidence of polymeric
      residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-microm
      microparticles caused adhesions in 83% of animals). Histology revealed chronic
      inflammation, with foreign body giant cells prominent with particles>5 microm in
      diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma
      irradiated) caused fewer adhesions (16.7%) with a similar incidence of residue.
      Nanoparticles (265 nm) of 90 kDa PLGA also caused much fewer adhesions (6.3% of
      animals), possibly because they were cleared from the peritoneum within 2 days,
      and sequestered in the spleen and liver, where foamy macrophages were noted. The
      effect of sterilization technique on the incidence of adhesion formation is also
      studied.

PMID- 16425241
TI  - In vivo study of novel biodegradable and osteoconductive CaO-SiO2-B2O3 glass
      ceramics.
AB  - To evaluate the possibility of novel CaO-SiO2-B2O3 glass-ceramics (CS10B) as a
      new bone replacement material, we compared the biodegradation and osteoconduction
      properties of CS10B, hydroxyapatite (HA), and tricalcium phosphate (TCP). Porous
      CS10B implants were prepared by the polymer sponge method. L5-6 single-level
      posterolateral spinal fusions were performed on 30 New Zealand white male
      rabbits. The animals were divided into three groups by implant material: CS10B,
      HA, and TCP. Radiographs were performed every 2 weeks. All animals were
      euthanized 12 weeks after surgery. The ratio of the area occupied by the ceramics
      by final and initial radiographs was calculated using radiomorphometric analysis.
      Uniaxial tensile strength was determined from seven cases in each group. The
      ratio of the area occupied by HA (88.7%+/-16.1%) was significantly higher than
      the others (p<0.005), and the ratio of the area occupied by CS10B (28.2%+/-9.3%)
      was significantly lower than those of HA and TCP (37%+/-9.6%, p<0.05). The mean
      values of the tensile strengths of the CS10B (182.7+/-19.9 N) and HA (191.4+/
      33.5 N) were significantly higher (p<0.05) than that of TCP (141.1+/-28.2 N).
      CS10B had a fusion mass tensile strength similar to that of HA. Histological
      analysis confirmed that CS10B was well incorporated into the fusion mass. These
      findings suggest that CS10B is a possible bone replacement material.

PMID- 16425242
TI  - Biological stability and osteoconductivity in rabbit tibia of pulsed laser
      deposited hydroxylapatite coatings.
AB  - A comparative study of the biological stability and the osteoconductivity of
      hydroxylapatite (HA) coatings produced by pulsed laser deposition (PLD) and
      plasma spraying (PS) was conducted. Three different implant groups were used:
      grit-blasted titanium rods coated with HA-PLD (2-microm-thick), grit-blasted
      titanium rods coated with HA-PS (50-microm-thick), and uncoated. Implantation
      took place into the proximal tibia of 12 mature New Zealand White rabbits for 24
      weeks. Samples were evaluated using descriptive histology and histomorphometry.
      While HA-PS implants showed considerable instability and reduction in thickness
      after 24 weeks, but no statistical difference to the titanium group, the HA-PLD
      group showed a significant higher amount of bone apposition (Scheffe test,
      p<0.05) than the other two groups, without signs of degradation or dissolution.
      Remarkably, after 6 months, the almost intact thin pulsed laser deposited coating
      could be observed by electron microscopy in extended areas.

PMID- 16425243
TI  - In vivo biostability of polysiloxane polyether polyurethanes: resistance to metal
      ion oxidation.
AB  - Polyether polyurethanes are subject to oxidation catalyzed by and through direct
      (redox) reaction with transition metal ions (cobalt), released by corrosion of
      metallic parts in an implanted device. Replacing part of the polyether with
      polysiloxane appears to reduce susceptibility to metal ion oxidation (MIO). In
      vitro studies indicated that polyurethanes containing 20-35% polysiloxane (PS-20
      and PS-35) are about optimum. We implanted tubing samples containing cobalt
      mandrels in the subcutis of rabbits for periods up to 2 years. After 2 years,
      only traces of microscopic cracks were seen on half the PS-35 samples, PS-20
      significantly delayed MIO, while the polysiloxane-free control was very severely
      degraded. Infrared spectroscopy established that polyether soft segment oxidation
      was occurring in PS-20. We could not directly evaluate oxidation in PS-35 because
      siloxane bands mask the aliphatic ether. Indirect FTIR evidence suggests that
      there is very slight polyether oxidation that develops early, and then seems to
      stabilize. The molecular weight of degraded PS-20 decreased. That of microcracked
      PS-35 decreased negligibly while that of undamaged PS-35 increased slightly after
      2-year in vivo. The polysiloxane-free control was profoundly degraded. PS-20 has
      much improved MIO resistance, while that for PS-35 is highly MIO resistant
      compared with its polysiloxane-free control.

PMID- 16425244
TI  - Vacuolated neuroblastoma cells mimicking FAB L(3) lymphoblasts in bone marrow
      aspirates.
AB  - Abundant cytoplasmic vacuolation of neuroblasts has been noted on bone marrow
      aspirate (BMA) smears of two patients with metastatic neuroblastoma. Occasional
      tumor cells were dispersed as individual cells as well as in clumps. These cells
      had basophilic cytoplasm and several nucleoli, reminiscent of L(3) lymphoblast
      morphology. Flow cytometric analysis of the bone marrow mononuclear cells and
      neuron-specific enolase staining of the bone marrow biopsy samples further
      distinguished the cells as neuroblasts. Cytoplasmic vacuolations of neuroblasts
      may be a feature of metastatic neuroblastoma cells in BMA smears.

PMID- 16425245
TI  - Salivary gland neoplasms in children: the experience of the Istituto Nazionale
      Tumori of Milan.
AB  - BACKGROUND: Epithelial salivary gland tumors are very uncommon in pediatric age.
      We report a series of 52 cases treated at the Istituto Nazionale Tumori of Milan,
      Italy, over a 30-year period. These results are presented in conjunction with a
      literature review of salivary tumors with a view to providing an up-to-date
      overview of the clinical course, prognosis, and treatment options for this rare
      tumor. PROCEDURE: Fifty-two cases of epithelial salivary tumors were reviewed and
      the clinical-pathological information concerning tumor characteristics, therapy,
      and follow-up were collected. Patients' age ranged between 4 and 18 years.
      RESULTS: The major salivary glands were the main site of tumor occurrence (79% of
      cases arose in parotid glands); 37 patients had benign tumors (pleomorphic
      adenoma), 15 had malignant tumors (12 mucoepidermoid carcinoma, 9 low grade). All
      the patients were treated by surgery; local relapses after parotidectomy were 4%
      and 25%, in benign and malignant tumors, respectively. When tumor enucleation was
      performed, recurrences occurred in 50% of benign neoplasms. At the time of the
      report, all patients with benign tumors were alive, 35(95%) without evidence of
      disease; only one patient with malignant tumor died of disease. CONCLUSIONS:
      Epithelial salivary glands tumor in children had different characteristics
      compared with their adult counterpart with respect to the frequency of histotypes
      and site of occurrence, but their prognosis seems to be similar. Parotidectomy
      (total or superficial) is the best choice for achieving good cure rates in both
      benign and malignant tumors.

PMID- 16425246
TI  - Fatal Fournier's gangrene in a young adult with acute lymphoblastic leukemia.
AB  - Fournier's gangrene (FG) is a fulminant necrotizing fasciitis of the external
      genitalia. Few reports of FG exist in patients with hematologic malignancies. We
      describe a case of fatal FG in a 21-year-old man with acute lymphoblastic
      leukemia who was receiving remission-induction chemotherapy. Despite early local
      surgery, administration of appropriate antibiotics, resurgery for wider
      debridement and aggressive ICU support he succumbed while pancytopenic to septic
      shock, 26 days after initiation of chemotherapy. Multi-drug resistant Pseudomonas
      aeruginosa was isolated from blood and scrotal cultures obtained at initial
      surgery. FG is a fulminant infection, especially in the face of profound
      cytopenias.

PMID- 16425247
TI  - Cell death in early neural life.
AB  - Programmed cell death is a relevant process in the physiology and pathology of
      the nervous system. Neuronal cell death during development is well characterized,
      and studies of this process have provided valuable information regarding the
      regulatory mechanisms of cell death in the nervous system. In the last few years,
      cell death occurring at earlier developmental stages and affecting proliferating
      neuroepithelial cells and recently born neuroblasts has been recognized. In this
      review we cover the observations on cell death in the early, proliferating stages
      of vertebrate neural development. Genetically modified mouse model systems and
      complementary in vivo approaches in other vertebrates have provided a solid basis
      for its relevance and contribution to normal neural development, as well as for
      the pathological consequences of its deregulation. However, the precise
      functional role of cell death remains a topic of debate.

PMID- 16425248
TI  - Apoptosis as an instrument in cardiovascular development.
AB  - Cell death as a phenomenon in embryonic development was first described over 100
      years ago. Approximately 30 years ago the process was named apoptosis, and its
      involvement is now recognized in many life processes, in virtually every animal
      species, and from fertilization to the death of an organism. In cardiovascular
      development, it coincides with major developmental processes in specific time
      windows. Both intrinsic (controlled by mitochondrial activity) and extrinsic
      (starting with death receptors) apoptotic pathways co-regulate developmental
      mechanisms. During cardiac development, many cell populations are recruited to
      the heart, where they differentiate into cardiomyocytes, fibroblasts, smooth
      muscle cells, endocardial and endothelial cells lining the inner surfaces, and
      epicardial cells lining the outer contours. In particular, neural crest-derived
      cell populations, which migrate to specific locations in the heart, are prone to
      apoptosis. During the complex geometric changes that occur in the primary heart
      tube and connected vessel segments, proper interaction of the respective cell
      populations guarantees the ensuing steps of differentiation. Growth factors,
      including endothelin, VEGF, and TGF-beta, as well as other factors, such as FasL,
      play dominant roles in these phases. Transgenic and knockout studies have
      provided strong evidence for aberrant patterns of apoptosis resulting in
      congenital malformations and syndromic malformations, including septation
      anomalies, interrupted aortic arch segments, coronary anomalies, and DiGeorge
      syndrome. Embryonic remodeling of the arterial system, including the coronary
      arteries, is accompanied by apoptosis patterns, the disruption of which results
      in severe malformations. It is interesting to note that hemodynamic factors, such
      as flow-driven shear stress, regulate the expression of genes that are important
      for signaling molecules such as endothelin and NO-synthase. In general, high
      shear stress protects against apoptosis, thus preventing the onset of disease
      processes in the fully-grown vasculature, and regulating the remodeling of the
      vascular system in the embryo.

PMID- 16425249
TI  - Teratogen-induced apoptotic cell death: does the apoptotic machinery act as a
      protector of embryos exposed to teratogens?
AB  - Considerable evidence has been collected demonstrating that many teratogens
      induce apoptotic cell death in embryonic structures that turn out to be malformed
      in fetuses and newborns. Apoptosis is a genetically regulated process that is
      realized by the activation of death and pro-survival signaling cascades, and the
      interplay between these cascades determines whether the cell exposed to apoptotic
      stimuli dies or survives. Therefore, there is intense interest in understanding
      how the apoptotic machinery functions in embryos exposed to teratogens. However,
      the interpretation of the results obtained remains problematic. The main problem
      is that excessive embryonic cell death, regardless of its nature, if
      uncompensated for, ultimately leads to maldevelopment or embryonic death.
      Therefore, we can easily interpret results when the intensity of teratogen
      induced cell death and the severity or incidence of teratogen-induced anomalies
      directly correlate with each other. However, when teratogen-induced cell death is
      not followed by the formation of anomalies, a usual explanation is that teratogen
      induced apoptotic cell death contributes to the renewal of teratogen-targeted
      cell populations by promoting the removal of injured cells. It is clear that such
      an explanation leaves vague the role of the anti-apoptotic signaling mechanism
      (and, hence, the apoptotic machinery as a whole) with respect to protecting the
      embryo against teratogenic stress. In this review, we summarize the data from
      studies addressing the function of the apoptotic machinery in embryos exposed to
      teratogens, and then we discuss approaches to interpreting the results of these
      studies. We hypothesize that activation of a proapoptotic signaling in teratogen
      targeted cell populations is a necessary condition for an anti-apoptotic
      signaling that counteracts the process of maldevelopment to be activated. If such
      a scenario is true, we need to modify our approaches to choosing molecular
      targets for studies addressing this topic.

PMID- 16425250
TI  - Molecular mechanisms of trophoblast survival: from implantation to birth.
AB  - Fetal development depends upon a coordinated series of events in both the embryo
      and in the supporting placenta. The initial event in placentation is appropriate
      lineage allocation of stem cells followed by the formation of a spheroidal
      trophoblastic shell surrounding the embryo, facilitating implantation into the
      uterine stroma and exclusion of oxygenated maternal blood. In mammals, cellular
      proliferation, differentiation, and death accompany early placental development.
      Programmed cell death is a critical driving force behind organ sculpturing and
      eliminating abnormal, misplaced, nonfunctional, or harmful cells in the embryo
      proper, although very little is known about its physiological function during
      placental development. This review summarizes current knowledge of the cell death
      patterns and molecular pathways governing the survival of cells within the
      blastocyst, with a focus on the trophoblast lineage prior to and after
      implantation. Particular emphasis is given to human placental development in the
      context of normal and pathological conditions. As molecular pathways in humans
      are poorly elucidated, we have also included an overview of pertinent genetic
      animal models displaying defects in trophoblast survival.

PMID- 16425251
TI  - Relevance of motoneuron specification and programmed cell death in embryos to
      therapy of ALS.
AB  - The molecular cues that generate spinal motoneurons in early embryonic
      development are well defined. Motoneurons are generated in excess and
      consequently undergo a natural period of programmed cell death. Although it is
      not known exactly how motoneurons compete for survival in embryonic development,
      it is hypothesized that they rely on the ability to access limited amounts of
      trophic factors from peripheral tissues, a process that is tightly regulated by
      skeletal muscle activity. Attempts to elucidate the molecular mechanisms that
      underlie motoneuron generation and programmed cell death in embryos have led to
      various effective strategies for treating injury and disease in animal models.
      Such studies provide great hope for the amelioration of human amyotrophic lateral
      sclerosis (ALS), a devastating progressive motoneuron degenerative disease. Here
      we review the clinical relevance of studying motoneuron specification and death
      during embryonic development.

PMID- 16425252
TI  - Proliferation and cornification during development of the mammalian epidermis.
AB  - The skin is the largest organ of the body and consists of the underlying dermis
      and outer epidermis. Proper embryonic development and continual renewal of the
      adult epidermis are essential to provide an impenetrable barrier against fluid
      loss and serve as our most important defense against insults from the external
      environment. During mammalian embryogenesis the epidermis develops from the
      surface ectoderm, which initially consists of a multipotent single-layer
      epithelium. Once these epithelial cells receive the appropriate developmental
      cues, they become committed to stratify, initiate a massive expansion program,
      and finally embark on a journey of terminal differentiation to produce the
      morphologically distinct layers of the epidermis. The culmination of this journey
      is the formation of an impervious cornified envelope via a highly specialized
      form of programmed cell death, termed "cornification" (reviewed in Candi et al.),
      which is distinct in many ways from the classic apoptotic pathways. The epidermal
      developmental program that is first seen in the fetus is recapitulated for the
      entire life of the organism. The basal layer of adult skin harbors stem cells,
      which can divide to produce daughter stem cells and transit amplifying (TA) cells
      that go on to differentiate and cornify (reviewed in Fuchs and Raghavan). In this
      review we summarize current knowledge about the molecular regulation of
      proliferation and cornification in the developing mammalian epidermis. We focus
      on events in the interfollicular epidermis, with special emphasis on
      transcriptional regulation by p63, Notch, NF-kappaB/IKK, Hox, AP-1, AP-2, and
      C/EBP factors. We end with a discussion about perturbations in epidermal
      proliferation and cornification as they pertain to human skin pathologies.

PMID- 16425253
TI  - N-Myc functions in transcription and development.
AB  - N-Myc is a member of the Myc family of proteins, which are best known for their
      potent oncogenic activities and association with a large proportion of human
      cancers. Intense scrutiny of the oncogenic properties of Myc family proteins over
      the last several decades has revealed a great deal about their transcriptional
      and oncogenic activities. Myc proteins have broad effects on transcription and
      can stimulate a variety of cell behaviors that contribute to the malignant
      phenotype. N-Myc and c-Myc also play essential functions during embryonic
      development, and loss of these proteins has deleterious effects in most, if not
      all, tissues and organ systems. What remains to be fully unraveled is the
      relationship between the diverse activities associated with deregulated and
      overexpressed Myc and their normal roles during embryonic development and tissue
      homeostasis. In this review I summarize our understanding of the transcriptional
      activities of Myc family proteins and the roles of N-myc in morphogenesis,
      particularly as they relate to cellular proliferation and apoptosis.

PMID- 16425254
TI  - Regulation of proliferation and apoptosis during development of the
      preimplantation embryo and the placenta.
AB  - The preimplantation embryo starts as a single cell, the zygote. The first cell
      divisions do not lead to volume expansion, but rather to an increasing number of
      small cells. At the morula stage the first two cell lineages differentiate into
      the trophoblast and the inner cells mass/embryoblast. During development of the
      preimplantation embryo, apoptosis occurs only after the onset of the embryonic
      genome. It has become clear that the development of a healthy child requires not
      only very high rates of proliferation and differentiation, but also apoptosis,
      which is a crucial mechanism for morphogenesis and the development of the inner
      organs. Furthermore, the generation of specific cell types, such as lens cells,
      erythrocytes, and thrombocytes, depends on the apoptosis pathways. This is also
      true later in gestation, when the trophoblasts form the placenta and provide the
      epithelial cover of the villous trees of the placenta. This layer is in direct
      contact with maternal blood and, as do all epithelia, displays a continuous
      turnover of cells. Thus, apoptosis is a normal constituent of survival in this
      layer as well, and changes in the regulation and rate of apoptosis have
      deleterious effects on the trophoblast and consequently the developing embryo or
      fetus. Here we present a very brief overview of the importance of apoptosis for
      the development of the preimplantation embryo and the maintenance of placental
      trophoblasts. Furthermore, we highlight what happens when regulation of
      proliferation or apoptosis fails in these systems, and attempt to show that
      apoptosis is only the consequence of poor embryo or trophoblast development --
      not its cause.

PMID- 16425255
TI  - Fate of the hypertrophic chondrocyte: microenvironmental perspectives on
      apoptosis and survival in the epiphyseal growth plate.
AB  - The goal of this review is to examine the fate of the hypertrophic chondrocyte in
      the epiphyseal growth plate and consider the impact of the cartilage
      microenvironment on cell survival and apoptosis. Early investigations pointed to
      a direct role of the hypertrophic chondrocyte in osteogenesis. The terminally
      differentiated cells were considered to undergo a dramatic change in shape, size,
      and phenotype, and assume the characteristics of an osteoblast. While some
      studies have supported the notion of transdifferentiation, much of the evidence
      in favor of reprogramming epiphyseal chondrocytes is circumstantial and based on
      microscopic evaluation of cells that are present at the chondro-osseous junction.
      Although these investigations provided a novel perspective on endochondral bone
      formation, they were flawed by the failure to consider the importance of stem
      cells in osseous tissue formation. Subsequent studies indicated that many, if not
      all, of the cells of the cartilage plate die through the induction of apoptosis.
      With respect to agents that mediate apoptosis, at the chondro-osseous junction,
      solubilization of mineral and hydrolysis of organic matrix constituents by
      septoclasts generates high local concentrations of ions, peptides, and glycans,
      and secreted matrix metalloproteins. Individually, and in combination, a number
      of these agents serve as potent chondrocyte apoptogens. We present a new concept:
      hypertrophic cells die through the induction of autophagy. In the cartilage
      microenvironment, combinations of local factors cause chondrocytes to express an
      initial survival phenotype and oxidize their own structural macromolecules to
      generate ATP. While delaying death, autophagy leads to a state in which cells are
      further sensitized to changes in the local microenvironment. One such change is
      similar to ischemia reperfusion injury, a condition that leads to tissue damage
      and cell death. In the growth cartilage, an immediate effect of this type of
      injury is sensitization to local apoptogens. These two concepts (type II
      programmed cell death and ischemia reperfusion injury) emphasize the importance
      of the local microenvironment, in particular pO(2), in directing chondrocyte
      survival and apoptosis.

PMID- 16425256
TI  - Prognostic impact of hematogenous tumor cell dissemination in patients with stage
      II colorectal cancer.
AB  - Adjuvant chemotherapy is not routinely recommended in patients with colorectal
      cancer stage UICC II. Some of these patients, however, develop recurrent disease.
      Therefore, valid prognostic criteria are needed to identify high-risk patients
      who might benefit from adjuvant therapy. Disseminated tumor cells, detected in
      blood and bone marrow, may prove to be a valid marker, however, the prognostic
      relevance of these cells remains debated. In our study, we examined the
      prognostic significance of disseminated tumor cells in blood and bone marrow of
      patients with stage II colorectal cancer. Ninety patients with potentially
      curative (R0) resection of colorectal cancer stage II were prospectively enrolled
      into the study. Bone marrow and blood samples were examined for disseminated
      tumor cells by CK 20 RT-PCR. Patient, tumor and treatment factors were analyzed
      as prognostic factors. Multivariate analysis confirmed tumor cell detection in
      blood (hazard ratio 2.1, p = 0.03) and T-category (hazard ratio 2.2, p = 0.02) to
      be independent prognostic factors for relapse-free survival. Tumor cell detection
      in postoperative blood samples (hazard ratio 7.7, p < 0.001) and number of
      removed lymph nodes (hazard ratio 6.4, p < 0.001) were independent prognostic
      factors for disease-specific survival. Detection of circulating tumor cells in
      blood samples of patients with stage II colorectal cancer identifies patients
      with poor outcome. This finding should be confirmed by further studies and could
      then be used as a basis for conducting a randomized trial evaluating the effect
      of adjuvant chemotherapy in stage II patients.

PMID- 16425257
TI  - Combined prophylactic and therapeutic cancer vaccine: enhancing CTL responses to
      HPV16 E2 using a chimeric VLP in HLA-A2 mice.
AB  - We identified the strategies to induce a CTL response to human papillomavirus
      (HPV) 16 E2 in HLA-A2 transgenic mice (AAD). A chimeric HPV16 virus-like particle
      (VLP) that includes full length HPV16 E7 and E2 (VLP-E7E2) was generated. The
      combination of E2 and E7 has the advantage that E2 is expressed in early
      dysplasia and neoplasia lesions, where E7 is expressed in more advance lesions.
      Since T cell response to E2 is less defined, we first evaluated the strategies to
      enhancing CD8(+) T cell responses to HPV E7, using different combinations of
      immune-modulators with VLP-E7E2. Data showed that the CTL response to E7 could be
      significantly enhanced by coinjection of GM-CSF and anti-CD40 antibodies with
      chimeric VLP-E7E2 without adjuvant. However, using the same combination, a low
      level of CD8(+) T cell response to E2 was detected. To enhance the CD8+ T cell
      response to E2, we analyzed T cell epitopes from E2 sequence. A heterogenous
      prime-boost with chimeric VLP-E7E2 and E2 peptides was performed. The data showed
      that the priming with chimeric VLP-E7E2, followed by boosting with E2 peptides,
      gave a better CTL response than 2 immunizations with E2 peptides. The enhanced
      immunity is due to the increase of CD11c(+) and CD11c(+) CD40(+) double positive
      dendritic cells in mice that received immune-modulators, GM-CSF and anti-CD40.
      Furthermore, the level of anti-L1 antibodies remains similar in mice immunized
      with chimeric VLP with/without immune-modulators. Thus, the data suggested that
      the chimeric VLP-E7E2 has a therapeutic potential for the treatment of HPV
      associated CINs and cancer without diminishing VLPs potential as a prophylactic
      vaccine by inducing anti-L1 antibodies against free virus.

PMID- 16425259
TI  - Prospective study of physical activity in different periods of life and the risk
      of ovarian cancer.
AB  - Only few studies have assessed the role of physical activity in the etiology of
      ovarian cancer, and the results have been inconclusive. We studied associations
      between physical activity and risk of ovarian cancer in 96,541 women aged 30-49
      at enrollment in a prospective study in Norway and Sweden. Participants reported
      physical activity level at ages 14, 30 and at enrollment, and participation in
      competitive sports. Complete follow-up through 2001/2002 was achieved by linkage
      to national registries. The relation between physical activity and ovarian cancer
      incidence was assessed using multivariate Cox proportional hazard models. During
      an average 11.1 years of follow-up, there were 264 ovarian cancer cases
      (including 81 borderline tumors) diagnosed at a mean age of 49 years. Highly
      physically active women at cohort enrollment had a similar risk of ovarian cancer
      as women reporting no activity (multivariate relative risk RR = 1.08, 95% CI 0.53
      2.18). Physical activity at age 30 or at age 14 did not either afford any
      protection from ovarian cancer, nor did a consistently high level of activity
      from younger ages until enrollment. Results were similar for invasive and
      borderline tumors, and for different subgroups of women classified according to
      other known risk factors for ovarian cancer. In our study of primarily
      premenopausal women, physical activity at different ages did neither reduce nor
      increase risk of ovarian cancer. In the context of the inconsistent scientific
      literature, our findings probably reflect that physical activity is not causally
      related with ovarian cancer.

PMID- 16425258
TI  - Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis.
AB  - Mortalin, also known as mthsp70/GRP75/PBP74, interacts with the tumor suppressor
      protein p53 and inactivates its transcriptional activation and apoptotic
      functions. Here, we examined the level of mortalin expression in a large variety
      of tumor tissues, tumor-derived and in vitro immortalized human cells. It was
      elevated in many human tumors, and in all of the tumor-derived and in vitro
      immortalized cells. In human embryonic fibroblasts immortalized with an
      expression plasmid for hTERT, the telomerase catalytic subunit, with or without
      human papillomavirus E6 and E7 genes, we found that subclones with spontaneously
      increased mortalin expression levels became anchorage-independent and acquired
      the ability to form tumors in nude mice. Furthermore, overexpression of mortalin
      was sufficient to increase the malignancy of breast carcinoma cells. The study
      demonstrates that upregulation of mortalin contributes significantly to
      tumorigenesis, and thus is a good candidate target for cancer therapy.

PMID- 16425260
TI  - Abstracts of the 15th International Congress of Comparative Endocrinology (ICCE),
      Boston, Massachusetts, USA, May 22-27, 2005.

PMID- 16425261
TI  - Developmental mechanisms underlying tooth patterning in continuously replacing
      osteichthyan dentitions.
AB  - The dentition of osteichthyans presents an astonishing diversity with regard to
      the distribution of teeth in the oral cavity, tooth numbers, arrangements,
      shapes, and sizes. Taking examples from three unrelated teleosts--the most
      speciose group of osteichthyans--and from the literature, this study explores how
      the initial tooth pattern is set up, and how this relates to the establishment
      and maintenance (or modification) of the tooth replacement pattern. In teleosts,
      first-generation teeth (the very first teeth in ontogeny to develop at a
      particular locus) are commonly initiated in adjacent or in alternate (odd and
      even) positions. The mechanisms responsible for these divergent developmental
      patterns remain to be elucidated, in particular, whether they reflect a field or
      local type of control. However, patterns of adjacent or alternate tooth
      initiation, set up by the first-generation teeth, can easily turn into
      replacement patterns where new teeth are initiated simultaneously every second,
      or even every third position, by synchronizing the formation of new first
      generation teeth to the formation of replacement teeth at older loci. Our
      observations suggest that, once established, the replacement pattern appears to
      be maintained, as a kind of "default" state. Variations and modifications in this
      pattern are nevertheless common and suggest that tooth replacement is under local
      control, exerted at the level of the initiation of replacement teeth. Further
      studies are needed to test the hypothesis that regular replacement patterns are
      more frequent in association with the plesiomorphic condition of extramedullary
      replacement (replacement on the surface of the dentigerous bone) and more rare in
      the derived condition of intramedullary replacement (replacement within the
      medullary cavity of the dentigerous bone).

PMID- 16425262
TI  - Associations between vitamin D, vitamin D receptor gene and the androgen receptor
      gene with colon and rectal cancer.
AB  - The transcriptional activity of the vitamin D receptor (VDR) gene is regulated,
      at least in part, by the androgen receptor (AR) gene. We evaluate how the number
      of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in
      conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580
      cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were
      used. Vitamin D intake and average hours of sunshine exposure interacted with AR
      genotype in men. Men with low vitamin D intake or low levels of sunshine exposure
      who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs
      for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of
      vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95%
      CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of
      developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39,
      0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR
      gene was associated with reduced risk of colon cancer among women with any allele
      of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR
      genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats
      (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the
      AR gene. These data provide support for the role of vitamin D and sunshine
      exposure in the etiology of colorectal cancer and suggest that AR gene may
      modulate the association.

PMID- 16425264
TI  - The outcome of children with acute myeloid leukemia (AML) post-allogeneic stem
      cell transplantation (SCT) is not improved by the addition of etoposide to the
      conditioning regimen.
AB  - BACKGROUND: Relapse remains a concern for children with AML undergoing allogeneic
      SCT, so in an effort to reduce the risk of relapse in these patients, we
      intensified our pre-SCT preparation by adding etoposide to the standard busulfan
      and cyclophosphamide regimen. PROCEDURE: We retrospectively analyzed the
      collected data and compared the two groups; Group A (n = 18) included patients
      who received busulfan 16 mg/kg plus cyclophosphamide 200 mg/kg (Bu/Cy), and Group
      B (n = 48) included patients who received busulfan 12 mg/kg, cyclophosphamide 90
      mg/kg in addition to etoposide 60 mg/kg (Bu/Cy/VP). The patients' characteristics
      were similar in the two groups. RESULTS: No significant difference in the overall
      outcome was noted; the 5-year overall survival was 50% and 53.3% for Groups A and
      B, respectively (P = 0.9). Similarly, the 5-year probability of relapse was 64.1%
      and 46.1% for Groups A and B, respectively (P = 0.38). The use of etoposide was
      not associated with increased toxicity. CONCLUSION: The addition of etoposide to
      the Bu/Cy regimen was well tolerated, but did not appear to improve the outcome.

PMID- 16425263
TI  - EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell
      carcinoma.
AB  - Tumor progression and recurrence of cervical cancer is associated with
      upregulation of matrix metalloproteinase 2 (MMP-2). We evaluated the location,
      origin and activity of MMP-2 in cervical squamous cell carcinomas in comparison
      with MT1-MMP (MMP-14), TIMP-2 and extracellular matrix metalloproteinase inducer
      (EMMPRIN). Positive immunostaining for MMP-2 in malignant cells was detected in
      83% of the patients. Two patterns of tumor cell MMP-2 staining were observed:
      either homogenous in all tumor cells or confined to the cells neighboring the
      stroma (tumor-border staining pattern, TBS). Fluorescence in situ zymography
      showed active MMP-2 mainly around tumor nodules displaying TBS. The MMP-2
      staining of TBS tumors correlated significantly with the presence of TIMP-2 and
      MT1-MMP, proteins involved in docking MMP-2 to the cell surface and essential for
      MMP-2 activation. In situ mRNA hybridization in TBS tumors demonstrated more
      abundant presence of MMP-2 mRNA in neighboring myofibroblasts than in the
      adjacent tumor cells. Moreover, the TBS MMP-2 pattern correlated with the
      presence of EMMPRIN (p = 0.023), suggesting that tumor cells induce MMP-2
      production in nearby stromal cells. This pro-MMP-2 could subsequently be
      activated on tumor cells via the presence of MT1-MMP and TIMP-2. The biological
      relevance of this locally activated MMP-2 was underscored by the observation that
      only the TBS pattern of MMP-2 significantly correlated with decreased survival.
      In conclusion, the colocalization of EMMPRIN, MT1-MMP and TIMP-2 in human
      cervical carcinomas seems to be involved in a specific distribution pattern of
      tumor cell bound MMP-2, which is related with local proteolytic activity and
      therefore might be associated with worse prognosis of the patients.

PMID- 16425265
TI  - Cancer incidence among pesticide applicators exposed to metolachlor in the
      Agricultural Health Study.
AB  - Metolachlor is one of the most widely used herbicides in the United States. We
      evaluated the incidence of cancer among pesticide applicators exposed to
      metolachlor in the Agricultural Health Study, a prospective cohort study of
      licensed pesticide applicators in Iowa and North Carolina. A total of 50,193
      pesticide applicators were included. Detailed information on pesticide exposure
      and lifestyle factors was obtained from self-administered enrollment
      questionnaires completed between 1993 and 1997; average length of follow-up was
      7.33 years. Two metolachlor exposure metrics were used : (i) lifetime days
      personally mixed or applied metolachlor and (ii) intensity-weighted lifetime days
      (lifetime days x an intensity level). Poisson regression analysis was used to
      estimate relative risks (RR) and 95% confidence intervals (95%CI) for cancer
      subtypes by tertiles of metolachlor exposure. No clear risk for any cancer
      subtype was found for exposure to metolachlor. A significantly decreased RR was
      found for prostate cancer in the highest category of lifetime days exposure (RR =
      0.59; 95%CI, 0.39-0.89) and in the second highest category of intensity-weighted
      lifetime days exposure (RR = 0.66; 95%CI, 0.45-0.97); however, the test for trend
      was not significant for either exposure metric. A nonsignificantly increased risk
      was found for lung cancer with lifetime days exposure in the highest category (RR
      = 2.37; 95%CI, 0.97-5.82, p-trend = 0.03) but not with intensity-weighted
      lifetime days. Given the widespread use of metolachlor and the frequent detection
      of metolachlor in both surface and ground water, future analyses of the AHS will
      allow further examination of long-term health effects, including lung cancer and
      the less common cancers.

PMID- 16425266
TI  - Analysis of biologic surrogate markers from a Children's Oncology Group Phase I
      trial of gefitinib in pediatric patients with solid tumors.
AB  - This trial evaluated the effect of gefitinib on the plasma circulating levels of
      epidermal growth factor receptor (EGFR), vascular endothelial growth factor
      (VEGF), matrix metalloproteinases (MMP)-2 and -9 of patients treated on a
      pediatric Phase I trial. Complete plasma correlative studies were obtained from
      16 of the 25 enrolled patients. There was a trend for lower MMP-2 baseline levels
      in patients with partial response or stable disease. The Ewing sarcoma from the
      only patient with partial response lacked egfr mutations. Gefitinib did not
      induce any significant variation in the levels of the assessed parameters, and
      none of these determinations showed significant predictive or prognostic value.

PMID- 16425267
TI  - Ultrastructure of tarsal sensilla and other integument structures of two
      Pseudocellus species (Ricinulei, Arachnida).
AB  - Ricinuleids are one of the least investigated groups of Arachnida. In particular,
      knowledge of their ultrastructure is poor. Observations of the distal tarsomeres
      of ricinuleids show differences in their shape and equipment of surface
      structures. Legs I and II are used by the Ricinulei to explore their surroundings
      with tentative movements. The tarsomeres of these legs show similarities in shape
      and surface structures that distinguish them from those of legs III and IV. In
      this study, 11 different structures of the tarsomere surfaces of two cave
      dwelling species, Pseudocellus pearsei and P. boneti from Mexico, were
      investigated for the first time with scanning and transmission electron
      microscopy and discussed regarding their possible function: 1) a single treelike
      ramifying seta resembles a no pore single-walled (np-sw) sensillum; 2) setae
      occurring in a small number and possessing a bipartite shaft represent terminal
      pore single-walled (tp-sw) sensilla. The surface of the proximal half of the
      shaft shows small branches. The distal half has a smooth surface; 3) long setae
      with conspicuous longitudinal lamellae show characteristics of chemoreceptive
      wall pore single-walled (wp-sw) sensilla; 4) frequent small wp-sw sensilla with
      flat and irregular lamellae; 5) very short wp-sw sensilla occurring solitary or
      in groups; 6) a few short setae with smooth surface correspond to wp-sw sensilla;
      7) a single short clubbed seta articulating in a flat pit is considered to be a
      np-sw sensillum; 8) common long setae with a pointed tip show characteristics of
      mechanoreceptive np-sw sensilla; 9) ventral setae with adhesive and
      mechanosensory function are accompanied by multicellular "class III" glands; 10)
      slit organs with mechanoreceptive function; and 11) dome-like tubercles with no
      indication of sensorial function. Several of these sensilla form a sensory field
      on the dorsofrontal surface which is particularly pronounced on the distal
      tarsomeres of legs I and II.

PMID- 16425269
TI  - Air pollution and childhood cancer: a review of the epidemiological literature.
AB  - The authors evaluated support in the literature for the hypothesis that ambient
      air pollution causes childhood cancer. The PubMed database was searched for
      original articles, which were reviewed for evidence of a relation with the main
      types of childhood cancer, using criteria including sample size, magnitude and
      precision of relative risk estimates, presence of a dose-response pattern and
      potential for bias. The hypothesis has been studied almost entirely with respect
      to traffic-related air pollution. Since derivation of the hypothesis from 2 case
      control studies in Denver, USA, two further case-control studies have provided
      new positive evidence and 4 case-control and 7 ecological studies mainly negative
      evidence. The 4 case-control studies providing positive evidence were relatively
      small and tended to have more methodological limitations than those showing no
      association. Publication bias is possible. The weight of the epidemiological
      evidence indicates no increased risk for childhood cancer associated with
      exposure to traffic-related residential air pollution. Nevertheless, the limited
      number of studies, the methodological limitations of both positive and negative
      studies and the absence of consistency in the results obviate a firm conclusion
      of no effect. In particular, nondifferential misclassification of exposure might
      have masked true, weak associations.

PMID- 16425270
TI  - APE1 genotype and risk of bladder cancer: evidence for effect modification by
      smoking.
AB  - Apurinic/apyrimidinic (AP) sites are common mutagenic and cytotoxic DNA lesions
      that arise from the loss of normal bases. APE1, the major AP endonuclease of
      human cells, plays a central role in the repair of AP sites through both its
      endonuclease and phosphodiesterase activities. A common APE1 polymorphism, a T-
      >G transversion (Asp 148 Glu), was previously shown to be associated with risk of
      lung cancer, an association that was modified by cigarette smoking. To explore
      the association between APE1 genotype, smoking and bladder cancer risk, we
      examined data from an existing case-control study of bladder cancer patients (n =
      239) and control individuals (n = 215) recruited from urology clinics at 2
      hospitals in North Carolina. Genotype at the polymorphic site was determined
      using allele-specific primer extension reactions, followed by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. We found no overall
      association between APE1 genotype and bladder cancer risk. In stratified
      analyses, however, a positive association with risk was observed with an
      increasing number of Glu alleles among never smokers, but not among smokers (p
      value for interaction = 0.005). We can speculate that small allelic differences
      that are apparent in never smokers are obscured by the large amount of DNA damage
      found in smokers. Given the lack of established biological mechanisms, and
      suboptimal numbers of subjects in some exposure categories, our findings should
      be interpreted cautiously.

PMID- 16425272
TI  - Ultrastructure and functional organization of mouthpart sensory setae of the
      spiny lobster Panulirus argus: new features of putative mechanoreceptors.
AB  - In comparison with other decapods, the Caribbean spiny lobster Panulirus argus
      has little diversity in the external morphology of the setae on the mouth
      apparatus. In mouthpart areas that frequently touch food items only two types of
      setae can be distinguished: simple setae and cuspidate setae. Simple setae are by
      far more numerous. The ultrastructural data presented here show that both types
      of seta are bimodal, in that they both contain mechano- and chemosensory cells as
      indicated by morphological features. The morphological features divide the
      sensory cells into three types: type 1, which has a mechanosensory appearance;
      type 2, which has a chemosensory appearance; and type 3, which is believed to be
      a mechanoreceptor due to desmosomal connections to a scolopale. All three cell
      types were found in all examined setae. In an earlier study the simple setae were
      found to contain two types of mechanosensors: bend-sensitive cells and
      displacement-sensitive cells. The morphological arrangement of the outer
      dendritic segment described in the present study cannot explain this division.
      Instead, it is suggested that the difference in sensitivity is caused by a
      differential arrangement of their stretch-sensitive ion channels. This hypothesis
      also provides an explanation for the earlier observation that only bend cells
      respond to changes in osmolarity.

PMID- 16425271
TI  - Asparagine depletion after pegylated E. coli asparaginase treatment and induction
      outcome in children with acute lymphoblastic leukemia in first bone marrow
      relapse: a Children's Oncology Group study (CCG-1941).
AB  - PURPOSE: Re-induction outcomes vary for children with acute lymphoblastic
      leukemia (ALL) and marrow relapse. We explored possible relationships among
      asparaginase (ASNase) activity levels, asparagine (ASN) depletion, anti-ASNase
      antibody titers, and response to re-induction therapy in children and adolescents
      with ALL and an 'early' first marrow relapse. PATIENTS AND METHODS: After
      appropriate informed consent, we enrolled children and adolescents 1-21 years old
      with ALL and first marrow relapse within 12 months of completion of primary
      therapy. Induction therapy included intramuscular pegylated ASNase on Days 2 and
      16. We assessed ASNase activity, anti-ASNase antibody titers against native and
      pegylated (E. coli) ASNase, and amino acid levels of asparagine (ASN) and
      glutamine (GLN) on Days 0, 14, and 35 of re-induction. RESULTS: Ninety-three
      patients were at least partially assessable. Among 21 patients with M1 marrow
      status at Day 35, the median Day 14 ASN level was <1 microM. This is
      significantly lower than the median Day 14 ASN level of 4 microM in the group of
      patients with M3 marrow at Day 35. Neither Day 0 nor Day 35 antibody titers
      predicted ASNase enzymatic activity level on Day 14. Surprisingly, Day 14 ASNase
      activity did not predict serum ASN level on Day 14. However, Day 0 and Day 35
      anti-native ASNase antibody titers, and Day 0 anti-PEG ASNase antibody titers
      correlated positively with Day 14 serum ASN levels as one might expect from
      neutralizing antibody. Day 35 anti-PEG ASNase antibody titers did not.
      CONCLUSIONS: Patients with greater ASN depletion were more likely to achieve
      second remission in the context of six-drug therapy.

PMID- 16425273
TI  - Prediction of structured non-coding RNAs in the genomes of the nematodes
      Caenorhabditis elegans and Caenorhabditis briggsae.
AB  - We present a survey for non-coding RNAs and other structured RNA motifs in the
      genomes of Caenorhabditis elegans and Caenorhabditis briggsae using the RNAz
      program. This approach explicitly evaluates comparative sequence information to
      detect stabilizing selection acting on RNA secondary structure. We detect 3,672
      structured RNA motifs, of which only 678 are known non-translated RNAs (ncRNAs)
      or clear homologs of known C. elegans ncRNAs. Most of these signals are located
      in introns or at a distance from known protein-coding genes. With an estimated
      false positive rate of about 50% and a sensitivity on the order of 50%, we
      estimate that the nematode genomes contain between 3,000 and 4,000 RNAs with
      evolutionary conserved secondary structures. Only a small fraction of these
      belongs to the known RNA classes, including tRNAs, snoRNAs, snRNAs, or microRNAs.
      A relatively small class of ncRNA candidates is associated with previously
      observed RNA-specific upstream elements.

PMID- 16425274
TI  - Regional hypermethylation and global hypomethylation are associated with altered
      chromatin conformation and histone acetylation in colorectal cancer.
AB  - Regional DNA hypermethylation and global DNA hypomethylation are 2 epigenetic
      alterations associated with colorectal cancers. However, their correlation with
      microsatellite instability (MSI) and chromosomal instability (CIN) in colorectal
      cancer, and their relationship with chromatin conformation and histone
      modification are not clear. In this study, we analyzed regional and global
      methylation in 16 cell lines and 64 primary colorectal cancers. We found that MSI
      and CIN are 2 alternative events in most cell lines and tumors. Furthermore,
      regional hypermethylation and global hypomethylation are also alternative events
      in most cases. We also observed a strong correlation between MSI and regional
      hypermethylation and between CIN and global hypomethylation. We further analyzed
      chromatin conformation and histone acetylation in cell lines with CIN or MSI. CIN
      cancers had open chromatin conformation and enriched histone acetylation in
      repetitive as well as in gene-specific regions. MSI cancers, on the other hand,
      had closed chromatin conformation and low levels of histone acetylation. After a
      MSI cell line was treated with 5-aza-2'-deoxycytidine or trichostatin A, the
      closed chromatin conformation became open, and histone acetylation was enriched.
      These observations support our hypothesis that in colorectal cancer, regional
      hypermethylation and global hypomethylation are associated with altered chromatin
      conformation and histone acetylation, which might have a causal correlation with
      MSI and CIN, respectively.

PMID- 16425275
TI  - Classification of malignant pediatric renal tumors by gene expression.
AB  - BACKGROUND: The most common malignant renal tumors of childhood are Wilms tumor
      (WT), clear cell sarcoma of the kidney (CCSK), cellular mesoblastic nephroma
      (CMN), and rhabdoid tumor of the kidney (RTK). Because these tumors present
      significant diagnostic difficulties, the goal was to define diagnostically useful
      signatures based on gene expression. PROCEDURES: Gene expression analysis using
      oligonucleotide arrays was performed on a training set of 47 tumors (10 CCSKs, 9
      CMNs, 8 RTKs, and 20 WTs). Classifiers were developed for each tumor type using
      variations of compound covariate class predictor. The classifiers were applied to
      an independent test set of 72 tumors (3 CMN, 7 CCSK, 4 RTK, and 58 WT). Central
      review diagnosis was utilized as the gold standard. Correlation with the
      institutional diagnosis and qualitative estimation of confidence levels at the
      time of central review were noted. RESULTS: Within the training set, classifiers
      resulted in no errors when >10 genes were utilized. Top genes in each classifier
      were verified using quantitative reverse transcription-polymerase chain reaction
      (RT-PCR). Applying the classifiers to the test set, 71 of 72 tumors were
      correctly classified with a confidence level of >99%. The exception was
      incorrectly classified by the gold standard. In comparison, by histopathology 31%
      of the non-WT were not accurately classified by the local institution, and 29%
      were classified with <95% confidence on central review. CONCLUSIONS: Classifiers
      based on gene expression provide diagnostic confidence and accuracy greater than
      that of pathologic analysis alone. Tumors that show ambiguous gene expression
      profiles are those that are also pathologically and molecularly ambiguous and
      merit further analysis.

PMID- 16425276
TI  - Clinical significance of serum Th1-, Th2- and regulatory T cells-associated
      cytokines in adult T-cell leukemia/lymphoma: high interleukin-5 and -10 levels
      are significant unfavorable prognostic factors.
AB  - Patients with adult T-cell leukemia/lymphoma (ATLL) are in a severely
      immunocompromised state. Therefore, it is assumed that ATLL cells either express
      particular cytokines or induce their expression in host immune cells, disrupting
      the balanced production of cytokines and causing the host's immune system to
      break down. We examined the levels of serum cytokines including T helper type 1-
      (Th1-) associated cytokines [IFN-gamma, TNF-alpha, and interleukin (IL)-2], Th2
      associated cytokines (IL-4, -5 and -6) and regulatory T cell-associated cytokines
      (IL-10 and TGF-beta1) in 94 ATLL patients, 39 asymptomatic human T-cell
      lymphotropic virus type-1 (HTLV-1) carriers and 50 healthy adult volunteers, to
      clarify whether elevated levels of particular cytokines are associated with the
      prognosis of ATLL patients. On multivariate analysis, high IL-5 and IL-10 levels
      were independent and significant unfavorable prognostic factors among the ATLL
      patients. The IL-10 level significantly increased with disease progression at
      each step from asymptomatic HTLV-1 carrier to ATLL of the indolent variant
      (chronic and smoldering subtypes) to ATLL of the aggressive variant (acute and
      lymphoma subtypes). Furthermore, high IL-10 was significantly associated with
      high lactate dehydrogenase (LDH), indicating that the IL-10 level reflects the
      tumor burden. The IL-5 level was not associated with disease progression nor LDH.
      Among ATLL patients with the aggressive variant, high IL-5, but not high IL-10,
      was an independent and significant unfavorable prognostic factor on multivariate
      analysis. Measurement of serum IL-5 and IL-10 levels is useful for predicting the
      prognosis and for determining a suitable treatment strategy for ATLL patients.

PMID- 16425277
TI  - Polymorphic amino acids at codons 9 and 37 of HLA-DQB1 alleles may confer
      susceptibility to cervical cancer among Chinese women.
AB  - Cervical cancer is strongly associated with the infection by oncogenic forms of
      human papillomavirus (HPV). Although most women are able to clear HPV infection,
      some develop persistent infections that may lead to cancer, implying genetic
      susceptibility factors for malignant progression. To verify whether HLA class II
      DQB1 polymorphism is related to cervical cancer in Chinese population, HLA-DQB
      typing was carried out by PCR-SBT for 258 patients with cervical cancer and 284
      healthy controls, and the allele frequencies were calculated. In this study, HLA
      DQB1*060101 and DQB1*0602 alleles were significantly higher in the HPV16 infected
      patients with cervical cancer compared with healthy controls (chi(2) = 31.7452, p
      < 0.0001; chi(2) = 12.7838, p(c) = 0.0066), but DQB1*050201 allele was
      significantly lower (chi(2) = 26.2187, p < 0.0001). This result indicates that
      HLA-DQB1*060101 and DQB1*0602 may confer susceptibility to cervical cancer, and
      DQB1*050201 may contribute to the resistance to the development of cervical
      cancer among Chinese women. Sequence analysis reveals that DQB1*060101 allele
      encodes Leu at position 9 and Asp at position 37, unique to the susceptibility to
      cervical cancer, whereas the other DQB1 alleles encode Phe or Tyr and Ile or Tyr
      at the same two positions, respectively. This finding implies that polymorphic
      amino acids at the putative antigen binding residues 9 and 37 of HLA-DQB1 alleles
      may play an important role in the development of cervical cancer.

PMID- 16425279
TI  - The return of research results to participants: pilot questionnaire of
      adolescents and parents of children with cancer.
AB  - PURPOSE: The offer to return research results to participants is increasingly
      recognized as an ethical obligation, although few researchers routinely return
      results. We examined the needs and attitudes of parents of children with cancer
      and of adolescents with cancer to the return of research results. METHODS: Seven
      experts in research ethics scored content validity on parent and adolescent
      questionnaires previously developed through focus group and phone interviews. The
      questionnaires were revised and provided to 30 parents and 10 adolescents in a
      tertiary care oncology setting. RESULTS: The content validity index for
      individual questions and the overall questionnaires scored as 0.86 for both
      questionnaires. All 30 parents and 10 adolescents who agreed to participate
      returned questionnaires. The majority (>95%) indicated that they had a strong or
      very strong right to receive results. Letter or e-mail was a satisfactory means
      to return results described as good or neutral (66% parents, 100% adolescents)
      but more participants wished face-to-face disclosure of results with negative
      implications (50% parents, 60% adolescents). Very few wanted results disseminated
      through a Web site. The majority acknowledged the need for peer-review before
      disclosure (60% of adolescents and parents) but did not want "to be the last to
      know." CONCLUSIONS: Our data suggest that pediatric oncology patients and parents
      of children with cancer strongly feel that they have a right to research results,
      and that they wish to receive these in a timely manner.

PMID- 16425278
TI  - Fruits and vegetables and renal cell carcinoma: findings from the European
      prospective investigation into cancer and nutrition (EPIC).
AB  - We examined the association between fruits and vegetables and risk of renal cell
      carcinoma (RCC) in the European Prospective Investigation into Cancer and
      Nutrition (EPIC). Dietary intake data and complete follow-up information on
      cancer incidence were available for 375,851 participants recruited in EPIC
      centers of 8 countries. During an average follow-up of 6.2 years, 306 incident
      cases of RCC were identified. The associations of consumption of total
      vegetables, total fruits, combined total fruits and vegetables and specific
      subtypes of vegetables with RCC risk were analyzed using Cox proportional
      hazards, stratified by centre and adjusted for potential confounders. No
      significant associations between fruit and vegetable consumption and RCC risk
      were observed despite a wide range of intake. The estimated relative risks (95%
      confidence intervals [CI]) in men and women combined were 0.97 (0.85-1.11) per 40
      g increase in vegetable intake, 1.03 (0.97-1.08) per 40 g increase in fruit
      intake and 1.02 (0.93-1.11) per 80 g increase in fruit and vegetable intake
      combined. Among the vegetable subtypes, an inverse association was observed for
      root vegetables (RR per 8 g increase: 0.88; 95% CI: 0.78-0.99). These results
      suggest that total consumption of fruits and vegetables is not related to risk of
      RCC, although we cannot exclude the possibility that very low consumption is
      related to higher risk. The relationship of specific fruit and vegetable
      subgroups with RCC risk warrant further investigation.

PMID- 16425280
TI  - Possible mechanisms of the cancer-preventive activities of green tea.
AB  - The cancer-preventive activities of tea and some tea constituents, such as
      caffeine and (-)-epigallocatechin-3-gallate (EGCG), have been demonstrated in
      animal models. The mechanisms of action of the tea constituents have been
      extensively investigated, but the mechanisms for the cancer-preventive activity
      of tea are not clearly understood. This chapter discusses some of the reported
      studies on the green tea polyphenol, EGCG, and the major issues in the
      interpretation of these data. Among the different activities of EGCG observed in
      cell culture systems, we need to select the physiologically relevant ones based
      on the biological importance of the target as well as the effective concentration
      and whether the reaction can take place in vivo because of the limited
      bioavailability of EGCG. We also need to distinguish between primary and
      subsequent events. Possible artifacts should be recognized. The cancer-preventive
      mechanisms need to be validated in animal models or human samples.

PMID- 16425281
TI  - Beneficial effects of tea and its polyphenols against prostate cancer.
AB  - Tea, next to water, is the most widely consumed beverage in the world. Depending
      upon the level of fermentation, tea can be categorized into three types: green
      (unfermented), oolong (partially fermented), and black (highly to fully
      fermented). In general, green tea has been found to be superior to black and
      oolong tea in terms of antioxidant and health promoting benefits owing to the
      higher content of (-)-epigallocatechin-3-gallate. Tea polyphenols comprise about
      one-third of the weight of the dried leaf, and they exhibit biochemical and
      pharmacological activities including antioxidant activities, inhibition of cell
      proliferation, induction of apoptosis, cell cycle arrest and modulation of
      carcinogen metabolism. Several studies demonstrate that most tea polyphenols
      exert their effects by scavenging reactive oxygen species (ROS) since excessive
      production of ROS has been implicated in the development of a variety of ailments
      including cancer of the prostate gland (CaP). Using cell culture and animal model
      systems, molecular targets for these remarkable beneficial effects of green tea
      drinking on CaP prevention and therapy have been defined. Geographical and case
      control studies are showing that green tea drinking could afford CaP
      chemopreventive effects in human population. In this review we attempt to
      summarize the experimental as well as the epidemiological basis for the possible
      role of tea and its polyphenols for chemoprevention and chemotherapy of CaP.

PMID- 16425282
TI  - Chemoprevention of lung cancer by tea.
AB  - Tea is the second only to water as the most consumed beverage in the world. Both
      green and black teas have been studied for their health benefits for a variety of
      diseases, particularly cancer. Lung cancer is the predominant cause of cancer
      mortality in developed countries. Smokers' risk of lung cancer is 20 times that
      of persons who have never smoked. Epidemiological studies on the cancer
      preventive effects of tea produce inconsistent results, which could in part be
      attributed to the lack of a universal standard for tea preparations. However,
      most animal studies indicate that tea has strong chemopreventive effects against
      lung tumorigenesis. The reported mechanisms for chemopreventive activity of green
      tea are antioxidation, induction of phase II enzymes, inhibition of TNFalpha
      expression and release, inhibition of cell proliferation, and induction of
      apoptosis. Cell cycle arrest and apoptosis induced by green tea are probably the
      two most significant factors. Future studies are needed to determine how green
      tea affects the genes associated with cell cycle regulation and apoptosis during
      the mouse lung carcinogenesis process.

PMID- 16425283
TI  - New immunochemical fecal occult blood test with two-consecutive stool sample
      testing is a cost-effective approach for colon cancer screening: results of a
      prospective multicenter study in Chinese patients.
AB  - The purpose of the study is to evaluate a new immunochemical fecal occult blood
      test method (Hemosure IFOBT), and compare it to the Guaiac-based chemical method
      (CFOBT) for colorectal cancer detection. A hypothetical sequential method
      (SFOBT), in which IFOBT was used only as a confirmatory test for CFOBT, was also
      evaluated. A total of 324 patients were recruited from 5 major hospitals in
      Beijing, China. For each patient, 3 consecutive stool samples were collected for
      simultaneous CFOBT and IFOBT tests, followed by colonoscopic examination. We
      compared the sensitivity and specificity of the 3 methods (CFOBT, IFOBT and
      SFOBT) in two settings, with the first 2 consecutive samples versus all 3
      samples. Although the sensitivity for the detection of cancer and large (>20 mm)
      or multiple adenoma was similar for all 3 methods in the three-sample setting, in
      the two-sample setting IFOBT had higher sensitivity than SFOBT for detecting
      cancer (87.8% vs. 75.5%, respectively, p < 0.05) and large (>20 mm) or multiple
      adenomas (65.4% vs. 42.3%, respectively, p < 0.05). The IFOBT also had a higher
      specificity than the CFOBT (89.2% vs. 75.5%, respectively, p < 0.01) in "normal"
      individuals defined by colonoscopy in the three-sample setting. Comparing two
      sample setting to the three-sample setting, both CFOBT and SFOBT showed
      significant loss of sensitivity for the detection of cancer as well as adenoma,
      whereas the sensitivity for IFOBT did not change significantly. Overall, IFOBT
      with two-sample testing showed compatible sensitivity and specificity to the
      three-sample testing, and had a lower relative cost per cancer detected than the
      three-sample testing. In conclusion, the new Hemosure IFOBT with two consecutive
      stool samples appears to be the most cost-effective approach for colon cancer
      screening.

PMID- 16425284
TI  - A history of cancer in the husband does not increase the risk of breast cancer.
AB  - Spouses share the home environment, and dietary and other lifestyle habits.
      Furthermore, a cancer diagnosis in the husband is a stressful event for the wife
      also. Thus, a history of cancer in the husband may be an indicator of breast
      cancer risk. We investigated the issue in a large Italian multicentric case
      control study on 2,588 women with incident breast cancer and 2,569 female
      hospital controls, admitted for acute, non neoplastic diseases. The adjusted odds
      ratio (OR) was 1.0 (95% confidence interval, CI, 0.7-1.4) for a history of any
      type of cancer in the husband, 1.0 (95% 0.4-2.7) for stomach, 0.7 (95% 0.2-2.3)
      for intestinal (chiefly colorectal), 0.9 (95% CI 0.5-1.7) for lung, and 1.3 (95%
      CI 0.4-4.3) for prostate cancer. The OR was close to unity also when data were
      analyzed in separate strata of patient's or husband's age, patient's education,
      or vital status of the husband. This study suggests that women whose husband had
      a diagnosis of cancer are not at increased risk of breast cancer, although
      results for individual cancer sites should be interpreted with caution, due to
      small numbers.

PMID- 16425285
TI  - Prognostic impact of orotate phosphoribosyl transferase among 5-fluorouracil
      metabolic enzymes in resectable colorectal cancers treated by oral 5-fluorouracil
      based adjuvant chemotherapy.
AB  - Orotate phosphoribosyl transferase (OPRT) is the main enzyme that involves in
      phosphoribosylation of 5-fluorouracil (5-FU), an essential step that leads to
      tumor growth inhibition. In our study, the prognostic relevance of OPRT,
      thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in resectable
      colorectal cancer (CRC) patients treated by oral 5-FU were compared to further
      clarify the prognostic value of OPRT. Tumor tissue was collected from 90 CRC
      patients and the patients were followed for 5.2 years (Median). TS, DPD and OPRT
      activities in the extract of tumor tissue were determined enzymatically. The cut
      off value of OPRT (0.147 nmol/(min mg), TS (0.044 pmol/mg) and DPD (72.10
      pmol/(min mg) were determined by maximal chi(2) method. Among these 5-FU
      metabolic enzymes, only high OPRT group demonstrated significantly better disease
      free survival (DFS) (p = 0.0152) and better overall survival (p = 0.0078). In Cox
      regression analysis, node status (p < 0.0005) and OPRT (p = 0.044) were
      significant factors for DFS. OPRT activity in tumor tissue was a predictor of
      prognosis in resectable CRC patients treated by oral 5-FU-based adjuvant
      chemotherapy, and was useful to pick-up high risk patients independent from known
      prognosis factors.

PMID- 16425286
TI  - STAT3 ser727 phosphorylation and its association with negative estrogen receptor
      status in breast infiltrating ductal carcinoma.
AB  - Although it is known that STAT3 transcriptional activity is modulated by
      phosphorylation at serine residue 727, the role of STAT3 serine phosphorylation
      in breast cancer remains mostly unexplored. In this study, we examined the
      expression patterns of serine residue 727-phosphorylated STAT3 (p-ser727-STAT3)
      in breast infiltrating ductal carcinoma tissues and nearby noncancer tissues by
      using immunoblotting techniques, and correlated the expression profiles with
      clinicopathological characteristics. A significantly elevated p-ser727-STAT3
      expression was observed in 61.8% (42/68) of breast cancer tissues as compared to
      corresponding noncancer tissues (p < 0.001). Further, immunohistochemical
      analysis also showed an increased nuclear p-ser727-STAT3 staining in cancer
      lesions. The increased p-ser727-STAT3 expression in breast infiltrating ductal
      carcinoma tissues correlated significantly with negative estrogen receptor (ER)
      status, increased stage of cancer and increased tumor size (p = 0.001, 0.024 and
      0.014, individually). Intriguingly, we noticed that the expression levels of p
      ser727-STAT3 in ER-negative breast cancer cell lines were higher than those in ER
      positive breast cancer cell lines. In ER-positive MCF7 cells, treatment with
      ERalpha-specific siRNA increased, whereas treatment with anticancer drug
      tamoxifen decreased the expression of p-ser727-STAT3, phenomena not observed in
      ER-negative MDA-MB-231 cells. In conclusion, our results suggest that p-ser727
      STAT3 may be involved in the pathogenesis of breast cancer in an ER-dependent
      manner.

PMID- 16425287
TI  - Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer
      prevention study.
AB  - In vitro and in vivo studies have associated iron with both the initiation and
      promotional stages of carcinogenesis. We investigated whether iron was associated
      with colorectal cancer in a nested case-control study within the alpha
      tocopherol, beta-carotene cancer prevention study cohort. Exposure was assessed
      at baseline, using a 276-item food frequency questionnaire and a fasting serum
      sample. The study included 130 colorectal cancer cases (73 colon cancers and 57
      rectal cancers) and 260 controls. Conditional logistic regression was used to
      estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron
      intake was only reported for 4 cases and 18 controls; therefore, we were unable
      to obtain meaningful results for this variable. Comparing the highest to the
      lowest quartiles, there was an inverse association between serum ferritin and
      colorectal cancer risk (OR = 0.4, 95% CI = 0.2-0.9) and a suggestion of an
      inverse association between dietary iron and colorectal cancer risk (OR = 0.4,
      95% CI = 0.1-1.1). In addition, serum ferritin, serum iron and transferrin
      saturation were all inversely associated with colon cancer risk specifically (OR
      = 0.2, 95% CI = 0.1-0.7, p trend = 0.02; OR = 0.2, 95% CI = 0.1-0.9, p trend =
      0.05; OR = 0.1, 95% CI = 0.02-0.5, p trend = 0.003, respectively), whereas serum
      unsaturated iron binding capacity was positively associated with colon cancer
      risk (OR = 4.7, 95% CI = 1.4-15.1, p trend = 0.009). In summary, we found a
      significant inverse association between several serum iron indices and colon
      cancer risk.

PMID- 16425288
TI  - Differentiation-dependent expression of hypothetical proteins in the
      neuroblastoma cell line N1E-115.
AB  - Several protein cascades, including signaling, cytoskeletal, chaperones,
      metabolic, and antioxidant proteins, have been shown to be involved in the
      process of neuronal differentiation (ND) of neuroblastoma cell lines. No
      systematic approach to detect hitherto unknown and unnamed proteins or structures
      that have been predicted upon nucleic acid sequences in ND has been published so
      far. We therefore decided to screen hypothetical protein (HP) expression by
      protein profiling. Two-dimensional gel electrophoresis with subsequent matrix
      assisted laser desorption/ionization-time of flight mass spectrometry (MALDI
      TOF/TOF) identification was used for expression analysis of undifferentiated and
      dimethylsulfoxide-induced neuronally differentiated N1E-115 cells. We
      unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and
      Q8C5G2. A prefoldin domain in Q91WT0, a t-SNARE domain in Q9CXS1, and a
      bromodomain were observed in Q8C5G2. For the three remaining proteins, no
      putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily,
      CoPS, and ExPASy could be assigned. While two proteins were present in both cell
      lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells
      only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells
      exclusively. Herein, using a proteomic approach suitable for screening and
      identification of HP, we present HP structures that have been only predicted so
      far based upon nucleic acid sequences. The four differentially regulated HPs may
      play a putative role in the process of ND.

PMID- 16425290
TI  - Long-term morbidity of patients with early breast cancer after sentinel lymph
      node biopsy compared to axillary lymph node dissection.
AB  - BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is widely accepted
      as an excellent method in the management of early breast cancer in patients with
      clinically negative axillary lymph nodes. Since SLNB requires less traumatic
      surgery to the axilla than axillary lymph node dissection (ALND), it was assumed
      to result in reduced shoulder/arm morbidity. However, data on long-term morbidity
      after SNLB are sparse. The present study was set up to compare long-term
      arm/shoulder morbidity as well as oncological outcome after SLNB versus ALND in
      patients with early breast cancer. METHODS: Oncological outcome, objective
      shoulder/arm morbidity, and subjective complaints after SLNB or ALND for T1
      breast cancer were assessed after a minimum follow-up of 20 months. RESULTS: One
      hundred thirty four patients were included in the study. Thirty-one patients
      underwent SNLB only, 103 patients had SLNB followed by ALND or ALND only. Loss of
      strength and hypaesthesia were less frequent after SLNB. No lymph oedema occurred
      after SNLB without adjuvant radiotherapy. Subjective complaints concerning pain,
      hypaesthesia, and paresthesia were more common in the ALND group. No axillary
      recurrence developed in either group. CONCLUSIONS: Isolated SLNB in node-negative
      pT1 breast cancer patients is a highly efficient tool to reduce postoperative
      long-term morbidity without compromising the local control of the disease. The
      reported ameliorations should favour SLNB as staging and treatment modality in
      patients suffering from early breast cancer.

PMID- 16425291
TI  - Radiofrequency ablation of small breast cancer followed by surgical resection.
AB  - BACKGROUND: With the growing demand from patients for less-invasive procedures,
      the shift from surgical extirpation to ablative local control of breast tumors is
      an emerging focus in breast cancer care. This study was performed to determine
      the feasibility and safety of treating small breast cancer with radiofrequency
      (RF) ablation. METHODS: Patients with biopsy-proven invasive or non-invasive
      breast cancer underwent RF ablation under general anesthesia. Before RF ablation,
      all patients were confirmed to have a localized lesion using imaging modalities.
      Wide excision or total mastectomy with sentinel lymph node biopsy or axillary
      lymph node dissection was performed. The resected tumor was examined
      histologically with hematoxylin-eosin (H&E) and nicotinamide adenine dinucleotide
      diaphorase (NADH) staining. RESULTS: Ten patients completed the treatment without
      RF ablation-related complications. The mean tumor size was 1.1 cm (range: 0.5-2.0
      cm). Histological evaluation of the ablated tissue using H&E staining revealed a
      spectrum of changes ranging from complete coagulation necrosis of tumor cells to
      normal-appearing tumor cells. However, NADH-diaphorase showed no staining of
      viable tumor cells in the RF-ablated region in all of the patients. CONCLUSIONS:
      RF ablation is promising as a minimally invasive ablation technique in the local
      treatment of invasive or non-invasive breast cancer. However, further study is
      necessary before RF ablation can replace conventional breast conservation therapy
      for patients with small breast cancer.

PMID- 16425292
TI  - Distribution of human SNPs and its effect on high-throughput genotyping.
AB  - Utilizing the results of extensive single nucleotide polymorphism (SNP) studies
      in humans, stimulated by the International HapMap Project, we present evidence
      that SNPs are not randomly spaced across the genome, but are somewhat clustered.
      This observation has important consequences for assay design, since hidden
      variants in primer sites can affect the accuracy of data. Indeed, using data from
      the calibration exercises of the HapMap Project, we found instances in which
      primer site mutations caused allele dropout and other genotyping failures. Given
      the dynamic nature of SNP discovery, it was inevitable that SNPs would be
      identified in the primer sites of many assays used for HapMap genotyping. We
      found that assays with such primer site mutations were correlated with elevated
      rates of genotype failure and allele dropout. This suggests that taking nearby
      SNPs into account is important for optimal genotyping assay design.

PMID- 16425293
TI  - Characterization of vitellogenin in the shrimp Metapenaeus ensis: expression
      studies and hormonal regulation of MeVg1 transcription in vitro.
AB  - During gonad maturation, female shrimp accumulate the major egg yolk protein
      vitellin (Vn) in premolt stage, and the process of molting and reproduction is
      synchronized. Using a polyclonal anti-Vn antibody, immunopositive signals could
      be detected in the ovary and among the proteins secreted by the hepatopancreas by
      Western blot. In the ovary, Vn immunoreactivity was located in the posterior
      lobe. Hepatopancreas proteins with sizes identical to ovary vitellogenin (Vg)
      subunits (i.e., 78 and 157 kDa) were immunoreactive to the Vn antibody and these
      proteins included amino acid sequences identical to parts of the MeVg1 precursor.
      A major 7.8 kb MeVg1 transcript, was detected in the ovary. In the
      hepatopancreas, the transcripts were primarily small (<2.3 kb) and while the 7.8
      kb transcript which constitutes <50% of the total Vg mRNA. MeVg1 transcript could
      be detected in the hepatopancreas of juvenile females with a maximum level during
      late intermolt and early premolt. To study the effect of different hormones on
      expression of MeVg1, explant cultures of hepatopancreas and ovary were developed.
      Although several hormones (20-hydroxyecdysone, estradiol (ES), farnesoic acid
      (FA), juvenile hormone (JH) III, methyl farnesoate, and progesterone (PG))
      apparently stimulated MeVg1 gene expression, only FA consistently stimulated
      MeVg1 expression by the hepatopancreas explants, while both FA and 20
      hydroxyecdysone were stimulated ovarian explants. In summary, (i) Vg transcripts
      can be detected in both reproductive and nonreproductive females; (ii) the
      presence of large quantities of smaller Vg transcripts and the absence of a large
      Vg precursor from the hepatopancreas suggests that smaller MeVg1 transcripts
      provide an important contribution to Vg synthesis in shrimp. Our results suggest
      that there is differential processing of the MeVg1 precursor in the ovary and
      hepatopancreas of shrimp.

PMID- 16425294
TI  - Role of the basic helix-loop-helix protein ITF2 in the hormonal regulation of
      Sertoli cell differentiation.
AB  - Sertoli cells are a post-mitotic terminally differentiated cell population that
      forms the seminiferous tubules in the adult testis and provides the
      microenvironment and structural support for developing germ cells. During
      pubertal development, Sertoli cells are responsive to follicle-stimulating
      hormone (FSH) to promote the expression of differentiated gene products. The
      basic helix-loop-helix (bHLH) and inhibitors of differentiation (Id)
      transcription factors are involved in the differentiation of a variety of cell
      lineages during development. Both bHLH and Id transcription factors have been
      identified in Sertoli cells. A yeast two-hybrid screen was conducted using a rat
      Sertoli cell cDNA library to identify bHLH dimerization partners for the Id1
      transcription factor. The ubiquitous bHLH protein ITF2 (i.e., E2-2) was
      identified as one of the interacting partners. The current study investigates the
      expression and function of ITF2 in Sertoli cells. ITF2 was found to be
      ubiquitously expressed in all testicular cell types including germ cells,
      peritubular myoid cells, and Sertoli cells. Stimulation of cultured Sertoli cells
      with FSH or dibutryl cAMP resulted in a transient decrease in expression of ITF2
      mRNA levels followed by a rise in expression with FSH treatment. ITF2 expression
      was at its highest in mid-pubertal 20-day-old rat Sertoli cells. ITF2 was found
      to directly bind to negative acting Id HLH proteins and positive acting bHLH
      proteins such as scleraxis. Transient overexpression of ITF2 protein in cultured
      Sertoli cells stimulated transferrin promoter activity, which is a marker of
      Sertoli cell differentiation. Co-transfections of ITF2 and Id proteins
      sequestered the inhibitory effects of the Id family of proteins. Observations
      suggest ITF2 can enhance FSH actions through suppressing the inhibitory actions
      of the Id family of proteins and increasing the actions of stimulatory bHLH
      proteins (i.e., scleraxis) in Sertoli cells.

PMID- 16425295
TI  - Axillary recurrence in women with a negative sentinel lymph node and no axillary
      dissection in breast cancer.
AB  - OBJECTIVES: Sentinel lymph node biopsy (SLNB) is widely used for staging breast
      cancer. SLNB accurately determines axillary lymph node status with a low false
      negative rate. There remains concern that omitting axillary dissection may lead
      to recurrence in the axilla, and impact long term survival. The purpose of this
      study was to determine the frequency of axillary lymph node recurrence in
      patients who had a negative sentinel lymph node and did not undergo axillary node
      dissection. METHODS: Data was collected on all patients who had negative SLNB at
      Roswell Park Cancer Institute between July 1997 and June 2002. Demographics, type
      of operation, postoperative systemic, and radiation therapy, co-morbidity score,
      hormone receptor status, and the pathologic features of the tumor were abstracted
      for each patient. For each woman with recurrence, the dates of recurrence, the
      site(s) of recurrence, and the treatment for recurrence were recorded. RESULTS:
      With a median follow-up of 33 months, 15 of 335 (4.5%) women who had negative
      SLNBs and who did not undergo completion axillary dissection developed a cancer
      recurrence. Only two patients (0.6%) had an axillary recurrence. CONCLUSIONS: The
      rate of axillary recurrence following a negative sentinel node biopsy is the same
      or less than axillary lymph node dissection (ALND) alone. Concerns that omitting
      completion axillary dissection following a negative SLNB will increase the rate
      of axillary recurrence appear unfounded.

PMID- 16425296
TI  - Genomewide screening of DNA copy number changes in chronic myelogenous leukemia
      with the use of high-resolution array-based comparative genomic hybridization.
AB  - Chronic myelogenous leukemia (CML) evolves from an indolent chronic phase (CP)
      characterized by the Philadelphia chromosome. Without effective therapy, it
      progresses to an accelerated phase (AP) and eventually to a fatal blast crisis
      (BC). To identify the genes involved in stage progression in CML, we performed a
      genomewide screening of DNA copy number changes in a total of 55 CML patients in
      different stages with the use of the high-resolution array-based comparative
      genomic hybridization (array CGH) technique. We constructed Human 1M arrays that
      contained 3,151 bacterial artificial chromosome (BAC) DNAs, allowing for an
      average resolution of 1.0 Mb across the entire genome. In addition to common
      chromosomal abnormalities, array CGH analysis unveiled a number of novel copy
      number changes. These alterations included losses in 2q26.2-q37.3, 5q23.1-q23.3,
      5q31.2-q32, 7p21.3-p11.2, 7q31.1-q31.33, 8pter-p12(p11.2), 9p, and 22q13.1-q13.31
      and gains in 3q26.2-q29, 6p22.3, 7p15.2-p14.3, 8p12, 8p21.3, 8p23.2, 8q24.13
      q24.21, 9q, 19p13.2-p12, and 22q13.1-q13.32 and occurred at a higher frequency in
      AP and BC. Minimal copy number changes affecting even a single BAC locus were
      also identified. Our data suggests that at least a proportion of CML patients
      carry still-unknown cryptic genomic alterations that could affect a gene or genes
      of importance in the disease progression of CML. This article contains
      Supplementary Material available at http://www.interscience.wiley.com/jpages/1045
      2257/suppmat.

PMID- 16425297
TI  - How the Pernkopf controversy facilitated a historical and ethical analysis of the
      anatomical sciences in Austria and Germany: a recommendation for the continued
      use of the Pernkopf atlas.
AB  - Eduard Pernkopf's Topographical Anatomy of Man has been a widely used standard
      work of anatomy for over sixty years. International inquiries about the National
      Socialist (NS) political background of Eduard Pernkopf and the use of bodies of
      NS victims for the atlas were first directed at the University of Vienna in 1996.
      A public discussion about the further use of the book followed and led to the
      creation of the Senatorial Project of the University of Vienna in 1997. This
      historical research project confirmed the strong NS affiliation of Pernkopf and
      revealed the delivery of at least 1,377 bodies of executed persons to the
      Anatomical Institute of Vienna during the NS time. The possible use of these
      bodies as models cannot be excluded for up to half of the approximately 800
      plates in the atlas. In addition tissue specimens from NS victims were found and
      removed from the collections of the Viennese Medical School and received a burial
      in a grave of honor. The Pernkopf controversy facilitated the historical and
      ethical analysis of the anatomical sciences in Austria and Germany during the NS
      regime. The continued use of the Pernkopf atlas is not only justifiable but
      desirable as a tool in the teaching of anatomy, history, and ethics.

PMID- 16425298
TI  - Quantitative analysis of the GAL4/UAS system in Drosophila oogenesis.
AB  - The GAL4/UAS system is extensively used for targeted gene expression in
      Drosophila, but the strength of the GAL4 drivers and their effects on target
      genes are rarely quantified. Quantitative information about the strength of the
      perturbations introduced by the GAL4/UAS system would further expand the
      usefulness of the GAL4/UAS system in studying gene functions and developmental
      processes. We have developed an assay to determine the relative level of
      expression for target genes tagged with green fluorescent protein (GFP). Our
      assay enables the relative quantitation of fluorescent proteins within specific
      cell types and developmental time windows in living eggs/embryos, and permits the
      analysis of samples from a broad expression range. We illustrate the assay using
      a panel of four GAL4 drivers and three UAS responder lines in Drosophila
      oogenesis, discuss the issues associated with the interpretation of the
      quantitative data, and correlate our results with the analysis of the GAL4/UAS
      system at the transcript level. The imaging-based strategy described here can be
      used to quantify other GAL4 drivers in Drosophila and other organisms.

PMID- 16425300
TI  - Prognostic factors in node-positive carcinoma of the penis.
AB  - BACKGROUND: Lymph node metastasis is the most important prognostic factor in
      patients with carcinoma of the penis. In this article, we have reviewed the
      outcome of the patients with pathologic node-positive carcinoma of the penis
      after groin dissection performed at the Cancer Institute (WIA) between 1987 and
      1998. METHODS: The case records of all patients who underwent groin dissection
      for carcinoma of the penis between 1987 and 1998 were analyzed. RESULTS: Between
      1987 and 1998, 128 patients underwent groin dissections for carcinoma of the
      penis at Cancer Institute (WIA), Chennai. Out of them, 102 patients had
      pathologic node-positive disease. The 5-year overall survival (OS) for these
      patients was 51.1%. Patients with metastasis only to inguinal nodes had a 5-year
      OS of 64.6% whereas none of the patients with pelvic nodal metastasis survived
      for 5 years. Among the pathologically node-positive patients, the factors
      adversely influencing survival on multivariate analysis were bilateral nodal
      metastases, number of positive inguinal nodes, pelvic nodal metastasis, and
      extranodal extension. CONCLUSIONS: Groin dissection is an effective treatment for
      nodal metastasis from carcinoma of the penis. However, innovative approaches are
      needed for the subset of patients with dismal outlook.

PMID- 16425301
TI  - Expression of protease activated receptor-2 (PAR-2) in gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Recently, the four-kind cloning of the protease
      activated receptor (PAR) had been carried out. PAR-2 is activated by trypsin and
      it is supposed that PAR-2 participated in proliferation of the endothelial cell
      or in neovascularization. We considered whether the expression of PAR-2 has
      relevance to progression in gastric cancer. METHODS: Immunohistochemical study by
      the envision method was carried out on 183 samples of gastric cancer in the first
      department of surgery, University of Fukui, using anti-PAR-2 mouse monoclonal
      antibody and on 95 samples of them that were pointed out advanced gastric cancers
      by pathological diagnosis using anti-trypsin rabbit polyclonal antibody. Tissues,
      which were stained more than 20% of the tumor cells, were classified as PAR-2
      protein-positive. Correlation with immunostainings and clinicopathological
      factors was analyzed statistically. RESULTS: There were 77 (42.1%) carcinomas
      positive for PAR-2 expression. The PAR-2 expression was intensely strong on the
      cell membrane of primary cancer tissues. The expression of PAR-2 correlated with
      the depth of wall invasion, lymphatic invasion, venous invasion, and liver
      metastasis. The patients with PAR-2 expression-positive tumors had a significant
      poorer prognosis than those with expression-negative tumors. Univariate analyses
      identified PAR-2 expression as negative predictors. Multivariate analyses
      indicated that PAR-2 expression was not an independent factor. A positive
      reaction for trypsin was obtained in 45 (47.4%) patients. We found a significant
      correlation between PAR-2 immunostaining and trypsin immunostaining. CONCLUSION:
      The results of this study lead us to believe that expression of PAR-2 is
      concerned with progression of gastric cancer.

PMID- 16425302
TI  - Serum CEA as a predictor for the response to preoperative chemoradiation in
      rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Recent data suggest that good responders to
      preoperative chemoradiation (CRT) have a favorable prognosis in rectal cancer
      patients. The aim of this study was to investigate the predictive value of serum
      carcinoembryonic antigen (CEA) levels for the tumor response to preoperative CRT
      in rectal cancer patients. METHODS: The study comprised 141 rectal adenocarcinoma
      patients who underwent preoperative radiotherapy with 5-fluorouracil (FU) based
      chemotherapy, followed by radical surgery. The staging workup was consisted of
      endorectal ultrasound, abdominopelvic computed tomography scan, or magnetic
      resonance imaging. The outcome parameters were cancer-specific survival and
      disease-free survival. Pre-CRT clinicopathologic features, including age, gender,
      location of the tumor, clinical tumor (cT) classification, clinical nodal (cN)
      classification, and serum CEA levels were investigated as possible predictors for
      the response to preoperative CRT. RESULTS: Pathologic complete or near complete
      responses (good responders, GR) occurred in 26 (19%) patients, while partial or
      no response (poor responders, PR) occurred in the remaining 115 (81%) patients.
      GR showed better cancer-specific survival (P = 0.028) and disease-free survival
      rates (P = 0.011) than PR. Univariate analysis revealed that positive cN and
      elevated (>5 ng/ml) pre-CRT serum CEA levels are associated with poor tumor
      response to preoperative CRT. Using logistic regression analysis, elevated pre
      CRT serum CEA levels were the only significant predictor for the poor response to
      CRT (Odd ratio = 2.876, 95% confidence interval = 1.04-7.46, P = 0.041).
      CONCLUSIONS: Our data suggest that elevated pre-CRT serum CEA levels are
      associated with poor tumor response to CRT. Therefore, pre-CRT serum CEA levels
      provide useful information about tumor response to preoperative CRT in rectal
      cancer patients.

PMID- 16425303
TI  - Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2)
      in patients with colorectal carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Therapy of colorectal tumors (CRC) based on histology
      and clinical factors is insufficient to predict the evolution of each patient.
      The finding of molecular abnormalities able to differentiate subgroups of
      patients with bad prognosis will improve our ability to treat them successfully.
      Our purpose was to analyze retrospectively the prognostic input of E-cadherin,
      beta-catenin, metalloproteinases (MMPs) (7 and 9), and tissue inhibitors of
      metalloproteinases (TIMPs) (1 and 2) in patients with a follow-up period of 5
      years. METHODS: Antigen expression was analyzed by immunohistochemistry.
      Prognostic evaluation was performed with the multivariate proportional hazards
      model. RESULTS: We demonstrated a concomitant loss of E-cadherin and beta-catenin
      at membranous level and an abnormal accumulation of nuclear beta-catenin.
      Besides, we found that all MMPs and TIMPs studied were overexpressed in CRC
      tissue. There was no association between the expression of any of these molecules
      and the known clinical-pathological parameters employed in CRC pathology. A
      multivariate analysis demonstrated that the overall survival could be
      independently predicted by the loss of E-cadherin and the overexpression of TIMP
      2. CONCLUSIONS: The expression of E-cadherin and TIMP-2 could be relevant in
      determining the prognosis of CRC patients and providing a more accurate mechanism
      for their classification.

PMID- 16425304
TI  - Hybrid ileostomy.

PMID- 16425305
TI  - Deactivation mechanisms of chloroperoxidase during biotransformations.
AB  - Inactivation mechanisms of chloroperoxidase (CPO) from Caldariomyces fumago have
      been investigated with the aim of improving the practical utility of CPO for
      hydrocarbon oxidation. Deactivation studies in the presence of oxidants (i.e.,
      hydrogen peroxide and t-butyl hydroperoxide) indicated that CPO lost oxidation
      activity toward hydrocarbon substrates during dismutation of hydrogen peroxide.
      The loss of enzyme activity was accompanied by the apparent destruction of the
      heme rather than aggregation or denaturation of the apo-protein. The decrease of
      enzyme activity was significantly retarded by adding the radical scavenger t
      butyl alcohol at pH 4.1, or by optimizing the reaction pH. CPO retained greatest
      oxidation activity at pH 5-6, which may produce a more favorable ionization state
      of the key amino acid (Glu-183) and thus reduce radical formation. As a result of
      higher activity at pH 5-6, the total turnover numbers (TTN, defined as the amount
      of product produced over the catalytic lifetime of the enzyme) for the oxidation
      of toluene and o-, m-, p-xylenes in substrate/aqueous emulsion systems ranged
      from ca. 10% to 110% higher at pH 5.5 (20,000 to 45,000 mol product/mol enzyme)
      compared to pH 4.1. Furthermore, TTNs of CPO increased with increasing turnover
      frequencies, indicating that higher activity toward reducing substrates reduces
      radical formation and stabilizes CPO toward inactivation by H(2)O(2). These
      findings demonstrate the important relationship between CPO stability and
      activity, and illustrate that large improvements in CPO activity and stability
      can be achieved through solvent engineering.

PMID- 16425306
TI  - Direct visualization of efficient energy transfer in single oligo(p-phenylene
      vinylene) vesicles.

PMID- 16425307
TI  - An Arabidopsis oxidosqualene cyclase catalyzes iridal skeleton formation by Grob
      fragmentation.

PMID- 16425309
TI  - Diastereoselective ring-rearrangement metathesis.

PMID- 16425308
TI  - A versatile method for Suzuki cross-coupling reactions of nitrogen heterocycles.

PMID- 16425310
TI  - Forces and torques during fracture reduction: Intraoperative measurements in the
      femur.
AB  - Reduction is a crucial step in fracture treatment. We determined intraoperative
      peak forces and torques during fracture reduction in seven patients with eight
      fractures of the femoral shaft. All fractures were temporarily stabilized by
      external fixation. Force and torque measurements were performed during the
      subsequent intramedullary nailing procedure. A three-dimensional load cell was
      attached to the distal femur fragment using two Schanz screws. All forces and
      torques were registered on-line during the reduction process. The maximum
      resulting force was 411 N, the maximum resulting torque 74 N x m. The highest
      force was observed along the shaft axis with 396 N for distraction. The maximum
      torque value was measured around the frontal axis, being 74 N x m for
      antecurvature. These results may assist the development of new reduction
      techniques and devices.

PMID- 16425311
TI  - Surgical procedures and lymphedema of the upper and lower extremity.
AB  - BACKGROUND: Lymphedema occurs in the upper and lower extremity, in a minority of
      patients, following axillary and groin dissections, respectively. Several
      technical operative factors have been implicated through the years whose relative
      significance remains unknown. METHODS: Retrospective review of the author's
      personal experience with axillary and groin dissections and review of the
      articles and results written on the author's series of patients. The results,
      specifically lymphedema, are reported in relation to components of each surgical
      procedure and the presence or absence of additional surgical procedures, e.g.,
      wide excision of the primary site when performed in the distal leg. RESULTS: In
      the axilla, skeletonization of the axillary vein, dissection up to and including
      Level III nodes, removal of the fat and nodes above the level of the axillary
      vein (exposing the brachial plexus), removal of pectoralis minor and all the
      axillary fat, exposing thus serratus anterior, latissimus dorsi and subscapularis
      are all technical components which do not cause lymphedema. It seems excessively
      thin flaps in axillary dissections may be the most likely cause for upper
      extremity lymphedema. The incidence of upper extremity lymphedema, in our
      experience, after axillary dissection is low (2%). For the lower extremity,
      skeletonization of the femoral and iliac vessels, in continuity dissection of the
      femoral and deep nodes (iliac and obturator), do not cause in themselves
      lymphedema (which occurs in 30% of the patients). The incidence of lymphedema
      increases with making thin flaps, with wide resection of a primary melanoma below
      the knee, postoperative incidence of cellulites, failure to follow a prophylactic
      regimen of leg elevation and compression stockings, and obesity. CONCLUSIONS:
      Lymphedema in the upper and lower extremity may be caused by making thin flaps
      during node dissection, the additional wide excision of primary sites in the
      distal half of the extremity, postoperative cellulitis, and failure to follow an
      antilymphedema regimen.

PMID- 16425312
TI  - Qualitative assessment of patient experiences related to extended pelvic
      resection for rectal cancer.
AB  - BACKGROUND: Patients with locally advanced rectal cancer (LARC) and locally
      recurrent rectal cancer (LRRC) represent a complex management challenge. While
      there is potential for cure in a subset of patients, the cost in terms of
      morbidity can be high. Few descriptions of the physical, psychological, social,
      and emotional experiences of these patients exist. METHODS: Face-to-face
      interviews were completed with ten LARC and LRRC patients treated with multimodal
      therapy that included surgery. Patient opinions and experiences were explored in
      depth until information redundancy and common themes were delineated using
      qualitative research methods. Clinical information was obtained from the
      database. RESULTS: Nine of the ten patients were male, seven had LARC, and the
      median age was 71. Six themes were identified from the patient interviews. Themes
      reflected patients' highly focused desire to seek wellness and cure, but also
      revealed misunderstanding of their disease biology, probability of cure,
      therapeutic options, and treatment morbidity. CONCLUSIONS: Patient experiences
      confirm that this is challenging treatment to complete, and that patient
      understanding of pre-operative information is incomplete. Our findings underscore
      the need for a multidisciplinary approach when managing this patient population,
      with emphasis on both supportive care needs and the technically skilled delivery
      of surgery, chemotherapy, and radiotherapy.

PMID- 16425313
TI  - Population-based analysis of lymphatic mapping and sentinel lymphadenectomy
      utilization for intermediate thickness melanoma.
AB  - BACKGROUND AND OBJECTIVES: Lymphatic mapping and sentinel lymphadenectomy (LM/SL)
      is the nodal staging procedure of choice for patients with intermediate thickness
      melanoma. We hypothesize that a significant portion of these patients are not
      undergoing LM/SL. We explore factors that influence use of LM/SL. METHODS:
      Analysis was performed of all incident cases of invasive cutaneous melanoma in
      North Carolina between January 1, 1999 and December 31, 2001. RESULTS: Three
      thousand four hundred and thirty-six cases of melanoma were reported for 1999
      2001. Two hundred and seventy-three cases (8%) were excluded due to metastases.
      Nine hundred and sixteen cases (29%) were excluded because the T classification
      was not reported. Of the remaining cases, 1,242 (55%) were intermediate thickness
      (T2-3); 48% (596/1,242) underwent LM/SL. Subjects >or=60 years old were less
      likely to receive LM/SL than subjects <60 years (39% vs. 55.4%, P < 0.001).
      Subjects with head/neck primary tumors were less likely to receive LM/SL than
      other subjects (33% vs. 51%, P < 0.001). Subjects with T3 tumors were more likely
      to receive LM/SL than those with T2 tumors (54% vs. 42%, P < 0.001). CONCLUSIONS:
      Half of all patients with intermediate thickness melanoma in North Carolina do
      not receive LM/SL. Use of LM/SL varies by patient age and primary tumor site.
      Further investigation is warranted to explore these differences.

PMID- 16425314
TI  - Two compounds containing the mixed germanium-vanadium polyoxothioanion
      [V14Ge8O42S8]12-.

PMID- 16425315
TI  - Copper-in-charcoal (Cu/C): heterogeneous, copper-catalyzed asymmetric
      hydrosilylations.

PMID- 16425316
TI  - Simultaneous determination of essential basic amino acids in pharmaceuticals by
      capillary isotachophoresis.
AB  - Capillary isotachophoresis (ITP) in cationic regime of the separation with
      conductometric detection has been used for the separation and determination of
      basic amino acids (arginine, histidine, and lysine) in pharmaceutical
      preparations. Several electrolyte systems of different compositions and pH were
      examined. The optimized ITP electrolyte system consisted of 10 mmol/L potassium
      acetate adjusted to pH 4.0 with acetic acid as the leading electrolyte with the
      electroosmotic-flow (EOF) suppressing additive, 0.2% (w/v)
      methylhydroxyethylcellulose (m-HEC), and 10 mmol/L beta-alanine as the
      terminating electrolyte. The proposed electrophoretic method was successfully
      validated. It was convenient for the sensitive, simple, rapid and highly
      reproducible assay of these amino acids. Good quantitation was obtained in short
      analysis times (a single analysis took about 10 min). The minimal sample
      pretreatment and low running costs make the proposed ITP method a good
      alternative to commonly used analytical methods. The obtained results suggest
      that the proposed method is suitable for routine assay of basic amino acids in
      pharmaceuticals.

PMID- 16425317
TI  - Self-assembled nanoreactors as highly active catalysts in the hydrolytic kinetic
      resolution (HKR) of epoxides in water.

PMID- 16425318
TI  - Synthesis and anti-inflammatory activities of new cyanopyrane derivatives fused
      with steroidal nuclei.
AB  - Thirteen new heterocyclic derivatives containing a cyanopyrane ring fused to a
      steroidal moiety were conveniently synthesized and screened for their anti
      inflammatory potencies comparable to that of the glucocorticoid prednisolone.
      Four compounds 5a, 5b, 6b, and 8 exhibited superior anti-inflammatory indices (in
      rats, protection against carrageenan induced edema and inhibition of plasma PGE).
      All the candidates were less toxic than the reference drug concerning LD(50)
      values. Synthetic steroidal structures fused to a substituted cyanopyrane ring
      seem to be a promising approach in search for novel leads for potent anti
      inflammatory agents.

PMID- 16425319
TI  - Tailored mesostructuring and biofunctionalization of gold for increased
      electroactivity.

PMID- 16425320
TI  - Dye-sensitizer effects on a Pt/KTa(Zr)O3 catalyst for the photocatalytic
      splitting of water.

PMID- 16425321
TI  - Formation of a dicyanotriorganophosphorane from the reaction of
      triphenylphosphane with phenylselenocyanate.

PMID- 16425322
TI  - Highly diastereo- and enantioselective copper-catalyzed domino reduction/aldol
      reaction of ketones with methyl acrylate.

PMID- 16425323
TI  - Prototype of a photoswitchable foldamer.

PMID- 16425324
TI  - Remote chiral induction in the organocatalytic hydrosilylation of aromatic
      ketones and ketimines.

PMID- 16425325
TI  - The origin of the halogen effect on reactivity and reversibility of Diels-Alder
      cycloadditions involving furan.

PMID- 16425326
TI  - 1,8-Bis(dimethylamino)naphthalene-2,7-diolate: a simple arylamine nitrogen base
      with hydride-ion-comparable proton affinity.

PMID- 16425328
TI  - Polyhedral interconversion coupled with proton transfer between an ammonium
      cation and the [Co(CO)4]- ion.

PMID- 16425327
TI  - Mild Ullmann-type biaryl ether formation reaction by combination of ortho
      substituent and ligand effects.

PMID- 16425329
TI  - Tetraarylphosphonium salts as solubility-control groups: phosphonium-supported
      triphenylphosphine and azodicarboxylate reagents.

PMID- 16425330
TI  - Nonlinear effects in Rh-catalyzed asymmetric olefin hydrogenation using mixtures
      of chiral monodentate P ligands.

PMID- 16425331
TI  - How does the initial alignment of mesogens affect the photoinduced bending
      behavior of liquid-crystalline elastomers?

PMID- 16425332
TI  - In situ imaging of electrochemically induced oxygen spillover on Pt/YSZ
      catalysts.

PMID- 16425333
TI  - Organic-inorganic Sn12 and organic Sn6 oxide-hydroxide clusters.

PMID- 16425334
TI  - Acid-induced conversions in open-framework semiconductors: from [Cd4Sn3Se13]6- to
      [Cd15Sn12Se46]14-, a remarkable disassembly/reassembly process.

PMID- 16425335
TI  - A microporous metal-organic framework for gas-chromatographic separation of
      alkanes.

PMID- 16425336
TI  - Regioselective carbon-carbon bond formation reactions between TCNE or TCNQ and a
      quinonoid ring.

PMID- 16425337
TI  - Pentarylene- and hexarylenebis(dicarboximide)s: near-infrared-absorbing
      polyaromatic dyes.

PMID- 16425338
TI  - A discrete PI--IP assembly: the large influence of weak interactions on the 31P
      NMR spectra of phosphane-diiodine complexes.

PMID- 16425339
TI  - Inhibitors of HIV-1 protease by using in situ click chemistry.

PMID- 16425340
TI  - Thermal [2+2] intramolecular cycloadditions of fuller-1,6-enynes.

PMID- 16425341
TI  - Crystal structures of Pigment Red 170 and derivatives, as determined by X-ray
      powder diffraction.

PMID- 16425342
TI  - Compression-inhibited pore formation of polyelectrolyte multilayers containing
      weak polyanions: a scanning force microscopy study.
AB  - Morphological changes of poly(acrylic acid)/poly(diallyldimethylammonium
      chloride) multilayers induced by low pH were investigated by scanning force
      microscopy. The weakened interaction between the charged polymer chains in the
      protonation process is believed to be the reason for this variation. Kinetic
      studies have shown that during protonation phase separation and dissociation of
      the multilayers took place successively. The compression of the multilayers,
      however, caused a transition of the multilayers from a rubbery state to a glassy
      state. As a result, the closely compacted multilayers lost their sensitivity to
      pH change. An increase of electrostatic and hydrophobic interactions, can
      decrease the free energy of the multilayers, and stabilize the films. By
      compression of the multilayers with a rubber stamp having geometric patterns,
      films with spatially localized pores were produced.

PMID- 16425343
TI  - Multipeak distributions of first passage times in bistable dynamics in a model of
      a thermochemical system.
AB  - A master equation is used to study transitions between the stable limit cycle and
      stable focus in the two-variable bistable system. The distribution function of
      the mean first passage time between these attractors and the relative dispersion
      of the mean first return time from the stable focus to itself as a function of
      the intensity of fluctuations are calculated and discussed. A coherence resonance
      is observed for the return time from the focus to itself.

PMID- 16425344
TI  - Characterization of maleuric acid derivatives on transgenic human monoclonal
      antibody due to post-secretional modifications in goat milk.
AB  - A fully human antibody to tumor necrosis factor-alpha was expressed in the
      mammary glands of transgenic goats. The goat expressed antibody (gAb) is
      heterogeneous and has several isoforms due to typical cellular post-translational
      modifications. In addition, one post-secretional modification on gAb was
      discovered by high-resolution cation exchange chromatography (CIEX). The presence
      of these variants in the final product was shown to be dependent upon the initial
      milk storage and traditional purification methodologies used. These observations
      allow for the development of new sample recovery and purification processes to
      eliminate these variants. Various enzymatic treatments were used to characterize
      different gAb heavy chain C-terminal lysine and sialic acid variants. In
      addition, an unknown derivative with the additional mass of 140 Da was found in
      transgenic gAb using mass spectrometry (MS). The modification sites were
      identified as the N-termini of gAb light chains and heavy chains using Q-TOF MS.
      Characterization of transgenic gAb isoforms was facilitated by utilizing
      different enzymes, CIEX and MS techniques. A maleuric acid modification on the N
      terminal portion of gAb was shown to be consistent with the available data
      characterizing this new derivative of transgenic gAb isoforms in goat milk.

PMID- 16425345
TI  - Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the
      estimation of nicorandil in human plasma.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method has been developed and validated for the estimation of nicorandil in human
      plasma. Nicorandil was extracted from human plasma using solid-phase extraction
      technique. Imipramine was used as the internal standard. A Betasil C18 column
      provided chromatographic separation of analytes followed by detection with mass
      spectrometry. The method involves a rapid solid-phase extraction from plasma,
      simple isocratic chromatography conditions and mass spectrometric detection that
      enables detection at nanogram levels. The proposed method has been validated for
      a linear range of 1.0-500.0 ng/mL with a correlation coefficient of > or =0.9993.
      The intra-run and inter-run precision and accuracy was within 10.0%. The overall
      recovery for nicorandil was 63.81%. The total run time was just 3.0 min.

PMID- 16425346
TI  - Immunological treatment of liver tumors.
AB  - Although multiple options for the treatment of liver tumors have often been
      described in the past, including liver resection, radiofrequency ablation with or
      without hepatic pump insertion, laparoscopic liver resection and the use of
      chemotherapy, the potential of immunotherapy and gene manipulation is still
      largely unexplored. Immunological therapy by gene manipulation is based on the
      interaction between virus-based gene delivery systems and dendritic cells. Using
      viruses as vectors, it is possible to transduce dendritic cells with genes
      encoding tumor-associated antigens, thus inducing strong humoral and cellular
      immunity against the antigens themselves. Both chemotherapy and radiation therapy
      have the disadvantage of destroying healthy cells, thus causing severe side
      effects. We need more precisely targeted therapies capable of killing cancer
      cells while sparing healthy cells. Our goal is to establish a new treatment for
      solid liver tumors based on the concept of cytoreduction, and propose an
      innovative algorithm.

PMID- 16425347
TI  - Management of functional dyspepsia: Unsolved problems and new perspectives.
AB  - The common characteristic criteria of all functional gastrointestinal (GI)
      disorders are the persistence and recurrence of variable gastrointestinal
      symptoms that cannot be explained by any structural or biochemical abnormalities.
      Functional dyspepsia (FD) represents one of the important GI disorders in Western
      countries because of its remarkably high prevalence in general population and its
      impact on quality of life. Due to its dependence on both subjective determinants
      and diverse country-specific circumstances, the definition and management
      strategies of FD are still variably stated. Clinical trials with several drug
      classes (e.g., proton pump inhibitors, H2-blockers, prokinetic drugs) have been
      performed frequently without validated disease-specific test instruments for the
      outcome measurements. Therefore, the interpretation of such trials remains
      difficult and controversial with respect to comparability and evaluation of drug
      efficacy, and definite conclusions can be drawn neither for diagnostic management
      nor for efficacious drug therapy so far. In view of these unsolved problems,
      guidelines both on the clinical management of FD and on the performance of
      clinical trials are needed. In recent years, increasing research work has been
      done in this area. Clinical trials conducted in adequately diagnosed patients
      that provided validated outcome measurements may result in better insights
      leading to more effective treatment strategies. Encouraging perspectives have
      been recently performed by methodologically well-designed treatment studies with
      herbal drug preparations. Herbal drugs, given their proven efficacy in clinical
      trials, offer a safe therapeutic alternative in the treatment of FD which is
      often favored by both patients and physicians. A fixed combination of peppermint
      oil and caraway oil in patients suffering from FD could be proven effective by
      well-designed clinical trials.

PMID- 16425348
TI  - Adenovirus expressing p27kip1 suppresses growth of established esophageal
      carcinoma xenografts.
AB  - AIM: To investigate the growth suppression of adenovirus expressing p27(kip1) on
      established esophageal tumors in nude mice. METHODS: Esophageal carcinoma
      xenografts in nude mice were established by tumor tissue mass transplantation.
      The successfully constructed recombinant adenoviral vectors carrying p27(kip1)
      gene (Ad-p27(kip1)) were directly injected into the esophageal tumors in nude
      mice. Compared to control group, the growth curve of tumor was drawn and the
      growth inhibition rate of tumor was calculated. The histology of tumors was
      examined by hematoxylin and eosin (H&E) staining. The expression of p27(kip1) and
      survivin was detected in tumors by immunohistochemical technique. RESULTS: The
      growth of tumors in gene therapy group with Ad-p27(kip1) was obviously suppressed
      compared to control group (0.42+/- 0.08 g vs 1.17+/- 0.30 g, t=6.39, P< 0.01),
      the inhibition rate of tumor growth reached 64.1%. Pathological detection showed
      that the tumors in nude mice were poorly differentiated esophageal squamous
      carcinoma. In addition, the expression of p27(kip1) was increased, while the
      expression of survivin was decreased in tumors after being transfected with Ad
      p27(kip1). CONCLUSION: p27(kip1) gene therapy mediated by adenovirus vector has a
      significant inhibitory effect on esophageal carcinoma in vivo. Up-regulated
      p27(kip1) expression and down-regulated survivin expression may be its important
      mechanisms.

PMID- 16425349
TI  - Clinical significance of CT-defined minimal ascites in patients with gastric
      cancer.
AB  - AIM: To study the clinical significance of minimal ascites, which was only
      defined by the CT and whose nature was not determined preoperatively, in the
      relationship with the peritoneal carcinomatosis. METHODS: The medical records and
      the dynamic CT films of 118 patients with gastric cancer were reviewed. Factors
      associated with peritoneal carcinomatosis were analyzed in 40 patients who had CT
      defined ascites of which the nature was surgically confirmed. RESULTS: Only 12.5
      25% of the CT-defined minimal ascites, whose volume was estimated to be less than
      50 mL, were associated with peritoneal carcinomatosis. When the estimated CT
      defined ascitic volume was 50 mL or more, peritoneal carcinomatosis was
      identified in 75-100%. When CT-defined lymph node enlargements were not found
      beyond the regional gastric area, perigastric invasions were not suspected, and
      the size of tumor was less than 3 cm, peritoneal carcinomatosis seemed
      significantly less accompanied at the univariate analysis. However, except for
      the minimal volume of CT-defined ascites in comparison with the mild or more,
      other factors were not confirmed multivariately. CONCLUSION: In the patients with
      gastric cancer, CT-defined minimal ascites alone is rarely associated with
      peritoneal carcinomatosis, if it does not accompany other signs suggestive of
      malignant seeding. Therefore, consideration of active curative resection should
      not be hesitated, if CT-defined minimal ascites is the only delusive sign.

PMID- 16425350
TI  - Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental
      exposure and risk of chronic gastritis and gastric cancer.
AB  - AIM: To evaluate the association between polymorphisms XRCC1 Arg194Trp and
      Arg399Gln and XRCC3 Thr241Met and the risk for chronic gastritis and gastric
      cancer, in a Southeastern Brazilian population. METHODS: Genotyping by PCR-RFLP
      was carried out on 202 patients with chronic gastritis (CG) and 160 patients with
      gastric cancer (GC), matched to 202 (C1) and 150 (C2) controls, respectively.
      RESULTS: No differences were observed among the studied groups with regard to the
      genotype distribution of XRCC1 codons 194 and 399 and of XRCC3 codon 241.
      However, the combined analyses of the three variant alleles (194Trp, 399Gln and
      241Met) showed an increased risk for chronic gastritis when compared to the GC
      group. Moreover, an interaction between the polymorphic alleles and demographic
      and environmental factors was observed in the CG and GC groups. XRCC1 194Trp was
      associated with smoking in the CG group, while the variant alleles XRCC1 399Gln
      and XRCC3 241Met were related with gender, smoking, drinking and H pylori
      infection in the CG and GC groups. CONCLUSION: Our results showed no evidence of
      a relationship between the polymorphisms XRCC1 Arg194Trp and Arg399Gln and XRCC3
      Thr241Met and the risk of chronic gastritis and gastric cancer in the Brazilian
      population, but the combined effect of these variants may interact to increase
      the risk for chronic gastritis, considered a premalignant lesion. Our data also
      indicate a gene-environment interaction in the susceptibility to chronic
      gastritis and gastric cancer.

PMID- 16425351
TI  - Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer.
AB  - AIM: To investigate the relationship between the expression levels of nm23 mRNA,
      CD44s, and CD44v6, and oncogenesis, development and metastasis of human gastric
      adenocarcinoma, colorectal adenocarcinoma, intraductal carcinoma of breast, and
      lung cancer. METHODS: Using tissue microarray by immuhistochemical (IHC) staining
      and in situ hybridization (ISH), we examined the expression levels of nm23 mRNA,
      CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62
      specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6 in 120
      specimens of intraductal carcinoma of breast and 20 specimens of normal breast
      tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23
      specimens of normal tissue adjacent to cancer. RESULTS: The expression of nm23
      mRNA in the tissues of gastric and colorectal adenocarcinoma was not
      significantly different from that in the normal tissues adjacent to cancer
      (P>0.05), and was not associated with the invasion of tumor and the pathology
      grade of adenocarcinoma (P>0.05). However, the expression of nm23 mRNA was
      correlated negatively to the lymph node metastasis of gastric and colorectal
      adenocarcinoma (r = -0.49, P<0.01; r = -4.93, P<0.01). The expression of CD44s in
      the tissues of gastric and colorectal adenocarcinoma was significantly different
      from that in the normal tissues adjacent to cancer (P<0.05; P<0.01). CD44v6 was
      expressed in the tissues of gastric and colorectal adenocarcinoma only, the
      expression of CD44v6 was significantly associated with the lymph node metastasis,
      invasion and pathological grade of the tumor (r = 0.47, P<0.01; r = 5.04,
      P<0.01). CD44s and CD44v6 were expressed in intraductal carcinoma of breast, the
      expression of CD44s and CD44v6 was significantly associated with lymph node
      metastases and invasion (P<0.01). However, neither of them was expressed in the
      normal breast tissue. In addition, the expression of CD44v6 was closely related
      to the degree of cell differentiation of intraductal carcinoma of breast (c2 =
      5.68, P<0.05). The expressional level of nm23 mRNA was closely related to the
      degree of cell differentiation (P<0.05) and lymph node metastasis (P<0.01), but
      the expression of nm23 gene was not related to sex, age, and type of histological
      classification (P>0.05). CONCLUSION: Patients with overexpression of CD44s and
      CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate
      and invasion. In addition, overexpression of CD44v6 is closely related to the
      degree of cell differentiation. Detection of the three genes is able to provide a
      reliable index to evaluate the invasion and metastasis of tumor cells.

PMID- 16425352
TI  - Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma.
AB  - AIM: To investigate the clinical significance of KL-6 as a tumor marker of HCC in
      two different ethnic groups with chronic liver disease consecutively encountered
      at outpatient clinics. METHODS: Serum KL-6 was measured by the sandwich enzyme
      immunoassay method using the KL-6 antibody (Ab) as both the capture and tracer Ab
      according to the manufacturer's instructions (Eisai, Tokyo, Japan). Assessment of
      alpha fetoprotein (AFP) and protein induced vitamin K deficiency or absence
      (PIVKA-II) was performed in both groups using commercially available kits.
      RESULTS: A significantly higher mean serum KL-6 (556+/-467 U/L) was found in HCC
      in comparison with non-HCC groups either with (391+/-176 U/L; P<0.001) or without
      (361+/-161 U/L; P<0.001) liver cirrhosis (LC). Serum KL-6 level did not correlate
      with either AFP or PIVKA-II serU/Levels. Using receiver operating curve analysis
      for KL-6 as a predictor for HCC showed that the area under the curve was 0.574
      (95%CI = 0.50-0.64) and the KL-6 level that gave the best sensitivity (61%) was
      found to be 334 U/L but according to the manufacturer's instructions; a cut-off
      point of 500 U/L was used that showed the highest specificity (80%) in comparison
      with AFP and PIVKA-II (78% vs 72% respectively). Combining the values of the
      three markers improved specificity of AFP for HCC diagnosis from 78% for AFP
      alone; 93% for AFP plus PIVKA-II to 99% for both plus KL-6 value (P<0.001). Mean
      serum alkaline phosphatase level was significantly higher in KL-6 positive (564+/
      475) in comparison with KL-6 negative (505+/-469) HCC patients (P = 0.021), but
      such a difference was not found among non-HCC corresponding groups. CONCLUSION:
      KL-6 is suggested as a tumor for HCC. Its positivity may reflect HCC-associated
      cholestasis and/or local tumor invasion.

PMID- 16425353
TI  - Modulation of gene expression in MHCC97 cells by interferon alpha.
AB  - AIM: To elucidate the molecular mechanisms of the inhibitory effects of IFN-alpha
      on tumor growth and metastasis in MHCC97 xenografts. METHODS: Three thousand
      international units per milliliter of IFN-alpha-treated and -untreated MHCC97
      cells were enrolled for gene expression analysis using cDNA microarray. The mRNA
      levels of several differentially expressed genes in cDNA microarray were further
      identified by Northern blot and RT-PCR. RESULTS: A total of 190 differentially
      expressed genes including 151 IFN-alpha-repressed and 39-stimulated genes or
      expressed sequence tags from 8,464 known human genes were found to be regulated
      by IFN-alpha in MHCC97. With a few exceptions, mRNA levels of the selected genes
      in RT-PCR and Northern blot were in good agreement with those in cDNA microarray.
      CONCLUSION: IFN-alpha might exert its complicated anti-tumor effects on MHCC97
      xenografts by regulating the expression of functional genes involved in cell
      metabolism, proliferation, morphogenesis, angiogenesis, and signaling.

PMID- 16425354
TI  - Detection of germline mutations of hMLH1 and hMSH2 based on cDNA sequencing in
      China.
AB  - AIM: To detect the germline mutations of hMLH1 and hMSH2 based on mRNA sequencing
      to identify hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS:
      Total RNA was extracted from peripheral blood of 14 members from 12 different
      families fulfilling Amsterdam criteria II. mRNA of hMLH1 and hMSH2 was reversed
      with special primers and heat-resistant reverse transcriptase. cDNA was amplified
      with expand long template PCR and cDNA sequencing analysis was followed. RESULT:
      Seven germline mutations were found in 6 families (6/12, 50%), in 4 hMLH1 and 3
      hMSH2 mutations (4/12, 33.3%); (3/12, 25%). The mutation types involved 4
      missense, 1 silent and 1 frame shift mutations as well as 1 mutation in the non
      coding area. Four out of the seven mutations have not been reported previously.
      The 4 hMLH1 mutations were distributed in exons 8, 12, 16, and 19. The 3 hMSH2
      mutations were distributed in exons 1 and 2. Six out of the 7 mutations were
      pathological, which were distributed in 5 HNPCC families. CONCLUSION: Germline
      mutations of hMLH1 and hMSH2 can be found based on cDNA sequencing so as to
      identify HNPCC family, which is highly sensitive and has the advantages of cost
      and time saving.

PMID- 16425355
TI  - Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver
      disease progression.
AB  - AIM: To observe the imbalance between T helper cell Th1 and Th2 cytokines in
      several chronic hepatitis disease at different stages of disease progression.
      METHODS: We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and
      the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RI and II) by the
      ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20
      chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C
      virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV)
      markers served as controls. RESULTS: Anti-HCV antibodies were found to be
      positive in 94% of HCC cases and 75% of CLD cases. On the other hand, HCV viremia
      was detected using RT-PCR in 67% of HCC cases and 65% of CLD cases. HBsAg was
      positive in 9% of HCC cases and 30% of CLD cases. Also bilharzial-Ab was positive
      in 55% of HCC cases, 65% of CLD cases and in 70% of asymptomatic carriers (ASC).
      HCC patients had significantly higher values of IL-2R, TNF-RII (P<0.001), and TNF
      RI (P>0.05), but lower TNFalpha (P<0.001) and IL-6 (P = 0.032) in comparison to
      ASC. But, in comparison to non-cancer controls, HCC patients had higher values of
      IL-2R, IL-6R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). CLD patients had
      higher IL-2R, TNF-RI, and TNF-RII (P<0.001) than ASC. But, in comparison to non
      cancer controls, CLD patients had higher values of IL-2R, TNF-RI and TNF-RII, but
      lower TNF-alpha (P<0.001). IL-10 was higher (though not significantly) in HCC and
      CLD patients than in symptomatic carriers and non-cancer controls. CONCLUSION:
      Liver disease progression from CLD to HCC due to HCV genotype-4 infection is
      associated with an imbalance between Th1 and Th2 cytokines. IL-2R, TNF-RI, and
      TNF-RII could be used as potential markers.

PMID- 16425356
TI  - Toll-like receptor 4 plays an anti-HBV role in a murine model of acute hepatitis
      B virus expression.
AB  - AIM: Toll-like receptor 4 (TLR4) has been shown to be important for bacterial
      infection, especially to lipopolysaccharide signaling. Its possible role in HBV
      infection is studied in the present study. MATERIALS AND METHODS: pHBV3.6
      plasmid, containing full-length HBV genome was used in the murine model of acute
      HBV expression by hydrodynamics in vivo transfection. TLR4 normal or mutant mouse
      strain was compared to investigate the possible role of TLR4 in acute HBV
      expression. RESULTS: After pHBV3.6 injection, the infiltrating leukocytes
      expressed TLR4 were observed nearby the HBsAg-expressing hepatocytes. The HBV
      antigenemia as well as the replication and transcription were higher in TLR4
      mutant C3H/HeJ mice than in normal C3H/HeN mice. The HBV-specific immune
      responses were impaired in the liver or spleen of the C3H/HeJ mice. Their
      inducible nitric oxide synthase (iNOS) expression on the hepatic infiltrating
      cells was also impaired. When adoptively transferring splenocytes from C3H/HeN
      mice to C3H/HeJ mice, the HBV replication was inhibited to the level as that of
      C3H/HeN. CONCLUSION: These results suggest that TLR4 plays an anti-HBV role in
      vivo through the induction of iNOS expression and HBV-specific immune responses
      after HBV expression.

PMID- 16425357
TI  - He Jie Tang in the treatment of chronic hepatitis B patients.
AB  - AIM: To explore the effect of He Jie Tang (decoction for medication) on serum
      levels of T lymphocyte subsets, NK cell activity and cytokines in chronic
      hepatitis B patients. METHODS: Eighty-five patients with chronic hepatitis B were
      divided randomly into two groups. Fifty patients in group I were treated with He
      Jie Tang (HJT) and 35 patients in group II were treated with combined medication.
      The levels of T-lymphocyte subsets (CD(3)(+), CD(4)(+), CD(8)(+)), NK cell
      activity, cytokines (TNF-alpha, IL-8, sIL-2R) were observed before and after the
      treatment. Another 20 normal persons served as group 3. RESULTS: The level of
      CD(4)(+) cells and NK cell activity were lower, whereas the level of CD(8)(+)
      cells in patients was higher than that in normal persons (t = 2.685, 3.172, and
      2.754 respectively; P<0.01). The levels of TNF-alpha, IL-8, and sIL-2R in chronic
      hepatitis B patients were higher than those in normal persons (t = 3.526, 3.170,
      and 2.876 respectively; P<0.01). After 6 months of treatment, ALT, AST, and TB
      levels in the two groups were obviously decreased (t = 3.421, 3.106, and 2.857
      respectively; P<0.01). The level of CD(4)(+) cells and NK cell activity were
      increased whereas the level of CD(8)(+) cells decreased (t = 2.179, 2.423, and
      2.677 respectively; P<0.05) in group I. The levels of TNF-alpha, IL-8, and sIL-2R
      in group I were decreased significantly after the treatment (t = 2.611, 2.275,
      and 2.480 respectively; P<0.05) but had no significant difference in group II
      after the treatment (t = 1.906, 1.833, and 2.029 respectively; P>0.05). The total
      effective rate had no significant difference between the two groups (c2 = 2.882,
      P>0.05) but the markedly effective rate was significantly different between the
      two groups (c2 = 5.340, P<0.05). CONCLUSION: HJT is effective in treating chronic
      hepatitis B. HJT seems to exert its effect by improving the cellular immune
      function and decreasing inflammatory cytokines in chronic hepatitis B patients.
      The function of HJT in protecting liver function in the process of eliminating
      virus needs to be further studied.

PMID- 16425358
TI  - Herpes simplex virus type 1 in peptic ulcer disease: an inverse association with
      Helicobacter pylori.
AB  - AIM: To assess the frequency of herpes simplex virus type I in upper
      gastrointestinal tract ulcers and normal mucosa with the modern and better assays
      and also with a larger number of well characterized patients and controls and its
      relationship to Helicobacter pylori(H pylori). METHODS: Biopsy specimens from 90
      patients (34 with gastric ulcer of the prepyloric area and 56 with duodenal
      ulcer) were evaluated. Biopsies from 50 patients with endoscopically healthy
      mucosa were considered as the control group. The method used to identify herpes
      simplex virus-1 (HSV-1) was polymerase chain reaction. H pylori was detected by
      the CLO-test and by histological method. RESULTS: Herpes simplex virus-1 was
      detected in 28 of 90 patients with peptic ulcer (31%) [11 of 34 patients with
      gastric ulcer (32.4%) and 17 of 56 with duodenal ulcer (30.4%)] exclusively close
      to the ulcerous lesion. All control group samples were negative for HSV-1. The
      likelihood of H pylori negativity among peptic ulcer patients was significantly
      higher in HSV-1 positive cases than in HSV-1 negative cases (P = 0.009). Gastric
      ulcer patients with HSV-1 positivity were strongly associated with an increased
      possibility of Helicobacter pylori negativity compared to duodenal ulcer patients
      (P = 0.010). CONCLUSION: HSV-1 is frequent in upper gastro-intestinal tract
      ulcers but not in normal gastric and duodenal mucosa. There is an inverse
      association between HSV-1 and H pylori infection.

PMID- 16425359
TI  - Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma
      in Barrett's esophagus: an Italian experience.
AB  - AIM: To evaluate endoscopic mucosal resection (EMR) in patients with high-grade
      dysplasia (HGD) and/or intramucosal cancer (IMC) in Barrett's esophagus (BE).
      METHODS: Between June 2000 and December 2003, 39 consecutive patients with HGD
      (35) and/or IMC (4) underwent EMR. BE >30 mm was present in 27 patients. In three
      patients with short segment BE (25.0%), HGD was detected in a normal appearing
      BE. Lesions had a mean diameter of 14.8+/-10.3 mm. Mucosal resection was carried
      out using the cap method. RESULTS: The average size of resections was 19.7+/-9.4
      x 14.6+/-8.2 mm. Histopathologic assessment post-resection revealed 5 low-grade
      dysplasia (LGD) (12.8%), 27 HGD (69.2%), 2 IMC (5.1%), and 5 SMC (-12.8%). EMR
      changed the pre-treatment diagnosis in 10 patients (25.6%). Three patients with
      SMC underwent surgery. Histology of the surgical specimen revealed 1 T0N0 and 2
      T1N0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo,
      respectively. A metachronous lesion was detected after 25 mo in one patient with
      HGD. Intra-procedural bleeding, controlled at endoscopy, occurred in four
      patients (10.3%). After a median follow-up of 34.9 mo, all patients remained in
      remission. CONCLUSION: In the medium term, EMR is effective and safe to treat HGD
      and/or IMC within BE and is a valuable staging method. It could become an
      alternative to surgery.

PMID- 16425360
TI  - Effect of cytokine gene polymorphism on histological activity index, viral load
      and response to treatment in patients with chronic hepatitis C genotype 3.
AB  - AIM: To investigate the association between cytokine gene polymorphism and
      disease status in chronic hepatitis C genotype 3 by liver biopsy, ALT, HCV RNA
      levels and response to treatment. METHODS: Patients with chronic hepatitis C
      genotype 3 were analyzed for single nucleotide polymorphisms of interleukin (IL)
      10, IL-1 beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha) and transforming growth factor-beta (TGF-beta) by polymerase chain
      reaction using sequence-specific oligonucleotide primers. Liver biopsies were
      assessed by modified histological activity index (HAI) scoring system using a
      scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the
      fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated
      with interferon alpha and ribavirin for 6 mo. Sustained virological response was
      assessed 6 mo after the completion of the treatment. RESULTS: Out of the 40
      patients analyzed, 26 were males. Mean age was 40.5+/-12.5 years (range 18-65
      years). The frequencies of different dimorphic polymorphisms based on single
      nucleotide substitution were as follows: IL-10-1082 G/A 85%, A/A 12.5%, G/G 2.5%;
      IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C
      90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, G/G 5%; TGF
      10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necro-inflammatory activity
      of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0,
      and G/G = 10.0 and the difference was significant (P = 0.029). The difference in
      the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 (P =
      0.079). The difference in the HAI seemed to be related to the presence of allele 
      1082G. For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C =
      2.2, and C/C = 1.0 (P = 0.020) though the inflammatory activity was not much
      different. No significant differences in HAI were noted among polymorphisms of
      other cytokines. Moreover, ALT and HCV RNA levels were not significantly
      different among different cytokine polymorphisms. There was a significant
      correlation of HAI and HCV RNA levels with the duration of disease. TGFbeta -10
      genotype CC patients had a better end of treatment response than those with other
      genotypes (P = 0.020). Sustained virological response to the treatment was not
      influenced by the cytokine polymorphism. No effect of other factors like viral
      load, degree of fibrosis, gender, steatosis, was observed on sustained
      virological response in this population infected with genotype 3. CONCLUSION:
      There is no significant correlation between cytokine polymorphisms and HAI except
      for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence
      hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C
      genotype 3. Sustained virological response in this genotype does not seem to be
      influenced by cytokine gene polymorphisms.

PMID- 16425361
TI  - Gastroprotective activity of Nigella sativa L oil and its constituent,
      thymoquinone against acute alcohol-induced gastric mucosal injury in rats.
AB  - AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute
      ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil
      (NS) and its constituent thymoquinone (TQ) in an experimental model. METHODS:
      Male Wistar albino rats were assigned into 4 groups. Control group was given
      physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol
      group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and
      fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight
      p.o) respectively 1 h prior to alcohol intake. One hour after ethanol
      administration, stomach tissues were excised for macroscopic examination and
      biochemical analysis. RESULTS: NS and TQ could protect gastric mucosa against the
      injurious effect of absolute alcohol and promote ulcer healing as evidenced from
      the ulcer index (UI) values. NS prevented alcohol-induced increase in
      thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation.
      NS also increased gastric glutathione content (GSH), enzymatic activities of
      gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise,
      TQ protected against the ulcerating effect of alcohol and mitigated most of the
      biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser
      extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue.
      CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa
      from acute alcohol-induced mucosal injury, and these gastroprotective effects
      might be induced, at least partly by their radical scavenging activity.

PMID- 16425362
TI  - Giardiasis in patients with dyspeptic symptoms.
AB  - AIM: To investigate the prevalence of giardiasis in patients with dyspeptic
      symptoms. METHODS: Clinical records of consecutive patients who attended
      Gastroenterology Department at Aga Khan University Hospital from January 2000 to
      June 2003 and had esophagogastroduodenoscopy (EGD) with duodenal biopsies and
      international classification of diseases 9th revision with clinical modifications
      (ICD-9-CM) coded with giardiasis were studied. RESULTS: Two hundred and twenty
      patients fulfilled the above criteria. There were 44% (96/220) patients who were
      giardiasis positive, 72% (69/96) of them were males and 28% (27/96) of them were
      females. There were 65% (81/124) males and 35% (43/124) females who were
      giardiasis negative. The mean age of patients with giardiasis was 28+/-17 years,
      while that of giardiasis negative patients was 40+/-18 years (P<0.001). In
      patients with giardiasis, abdominal pain was present in 71% (68/96) of patients
      (P = 0.02) and diarrhea in 29% (28/96) (P = 0.005); duodenitis in 25% (24/96) on
      EGD (P = 0.006) and in 68% (65/96) on histopathology (P = 0.002). CONCLUSION:
      Giardiasis occurs significantly in young people with abdominal pain, while
      endoscopic duodenitis is seen in only 25% of giardiasis positive cases, which
      supports routine duodenal biopsy.

PMID- 16425363
TI  - Plasma carnitine ester profile in adult celiac disease patients maintained on
      long-term gluten free diet.
AB  - AIM: To determine the fasting plasma carnitine ester in patients with celiac
      disease. METHODS: We determined the fasting plasma carnitine ester profile using
      ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed
      maturity onset celiac disease maintained on long term gluten free diet. RESULTS:
      The level of free carnitine did not differ as the celiac disease patients were
      compared with the healthy controls, whereas the acetylcarnitine level was
      markedly reduced (4.703 +/- 0.205 vs 10.227 +/-0.368 nmol/mL, P<0.01). The level
      of propionylcarnitine was 61.5%, butyrylcarnitine 56.9%, hexanoylcarnitine 75%,
      octanoylcarnitine 71.1%, octenoylcarnitine 52.1%, decanoylcarnitine 73.1%,
      cecenoylcarnitine 58.3%, lauroylcarnitine 61.5%, miristoylcarnitine 66.7%,
      miristoleylcarnitine 62.5% and oleylcarnitine 81.1% in the celiac disease
      patients compared to the control values, respectively (P<0.01). CONCLUSION: The
      marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other
      carnitine esters shows that the carnitine ester metabolism can be influenced even
      in clinically asymptomatic and well being adult celiac disease patients, and
      gluten withdrawal alone does not necessarily normalize all elements of the
      disturbed carnitine homeostasis.

PMID- 16425364
TI  - Investigation of fundo-antral reflex in human beings.
AB  - AIM: To examine the sensory and motor response(s) of the stomach following fundic
      distention and to assess whether cholinergic mechanisms influence these
      responses. METHODS: Fundic tone, gastric sensory responses and antral motility
      were evaluated in eight healthy volunteers after a probe with two sensors was
      placed in the antrum and a highly compliant balloon in the fundus. Isobaric
      balloon distentions were performed with a barostat. Study was repeated in six
      volunteers after intravenous atropine was given. RESULTS: Fundic distention
      induced large amplitude antral contractions in all subjects. The area under the
      curve was higher (P<0.05) during fundic distention. First sensation was reported
      at 12+/-4 mmHg, moderate sensation at 18+/-4 mmHg and discomfort at 21+/-4 mmHg.
      Discomfort was associated with a decrease in antral motility. After atropine was
      given, the area under the curve of pressure waves and fundic tone decreased
      (P<0.05). Sensory thresholds were not affected. CONCLUSIONS: Fundic balloon
      distention induces an antral motor response, the fundo-antral reflex, which in
      part may be mediated by cholinergic mechanisms.

PMID- 16425365
TI  - Validation of four Helicobacter pylori rapid blood tests in a multi-ethnic Asian
      population.
AB  - AIM: To validate the accuracy of four rapid blood tests in the diagnosis of
      Helicobacter pylori. METHODS: Consecutive dyspeptic patients scheduled for
      endoscopy at the National University Hospital, Singapore, were interviewed and
      had blood drawn for serology. The first 109 patients were tested with BM-test
      (BM), Pyloriset Screen (PS) and QuickVue (QV), and the next 99 subjects were
      tested with PS and Unigold (UG). Endoscopies were performed blinded to rapid
      blood test results and biopsies were taken for culture and rapid urease test.
      Urea breath tests were performed after endoscopies. The rapid blood test results
      were compared with four reference tests (rapid urease test, culture, serology,
      and breath test). RESULTS: The study population composed of 208 patients (mean
      age 43.1 years; range 18-73 years; 119 males; 174 Chinese). The number of
      evaluable patients for BM, QV, UG and PS were 102, 102, 95, and 197,
      respectively. The sensitivity and specificity, respectively were: PS 80.2%,
      95.8%; UG 55.9%, 100%; QV 43.3%, 100%; BM 67.2%, 97.1%. CONCLUSION: The rapid
      blood test kits showed high specificity and positive predictive value (97-100%),
      while sensitivity and negative predictive value ranged widely (43%-80% and 47%
      73%, respectively). Among test kits, PS showed the best sensitivity (80%), best
      negative predictive value (73%) and best negative likelihood ratio (0.207). PS
      had a specificity of 96%, positive predictive value of 97% and positive
      likelihood ratio of 19.1.

PMID- 16425366
TI  - Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid
      peroxidation, antioxidant enzyme systems and liver enzymes in carbon
      tetrachloride-treated rats.
AB  - AIM: To investigate the effects of Nigella sativa L (NS) and Urtica dioica L (UD)
      on lipid peroxidation, antioxidant enzyme systems and liver enzymes in CCl(4)
      treated rats. METHODS: Fifty-six healthy male Wistar albino rats were used in
      this study. The rats were randomly allotted into one of the four experimental
      groups: A (CCl(4)-only treated), B (CCl(4)+UD treated), C (CCl(4)+NS treated) and
      D (CCl(4)+UD+NS treated), each containing 14 animals. All groups received CCl(4)
      (0.8 mL/kg of body weight, sc, twice a week for 60 d). In addition, B, C and D
      groups also received daily i.p. injections of 0.2 mL/kg NS or/and 2 mL/kg UD oils
      for 60 d. Group A, on the other hand, received only 2 mL/kg normal saline
      solution for 60 d. Blood samples for the biochemical analysis were taken by
      cardiac puncture from randomly chosen-seven rats in each treatment group at
      beginning and on the 60th d of the experiment. RESULTS: The CCl(4) treatment for
      60 d increased the lipid peroxidation and liver enzymes, and also decreased the
      antioxidant enzyme levels. NS or UD treatment (alone or combination) for 60 d
      decreased the elevated lipid peroxidation and liver enzyme levels and also
      increased the reduced antioxidant enzyme levels. The weight of rats decreased in
      group A, and increased in groups B, C and D. CONCLUSION: NS and UD decrease the
      lipid per-oxidation and liver enzymes, and increase the anti-oxidant defense
      system activity in the CCl4-treated rats.

PMID- 16425367
TI  - Preoperative sorting of circulating T lymphocytes in patients with esophageal
      squamous cell carcinoma: its prognostic significance.
AB  - AIM: To elucidate the immunologic parameters for the outcome of patients with
      malignant tumors, especially esophageal squamous cell carcinoma (ESCC) associated
      with high malignant potential. METHODS: Clinicopathologic features were compared
      between patients with lower and higher CD4 and CD8 values as well as CD4/CD8
      ratio in peripheral blood. RESULTS: The survival rate of patients with higher CD4
      value was significantly better than that in patients with lower CD4 value (P =
      0.039). The survival rate of patients with higher CD8 value was significantly
      worse than that of patients with lower CD8 value (P = 0.026). Similarly, the
      survival rate of patients with higher CD4/CD8 ratio was significantly better than
      that of patients with lower CD4/CD8 ratio (P = 0.042). Additionally, multivariate
      analysis demonstrated that lower CD8 and lower CD4/CD8 ratio were factors
      independently associated with worse prognosis of patients. CONCLUSION: All the
      immunologic parameters can predict the outcome of patients with ESCC.

PMID- 16425368
TI  - DNA end binding activity and Ku70/80 heterodimer expression in human colorectal
      tumor.
AB  - AIM: To determine the DNA binding activity and protein levels of the Ku70/80
      heterodimer, the functional mediator of the NHEJ activity, in human colorectal
      carcinogenesis. METHODS: The Ku70/80 DNA-binding activity was determined by
      electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal
      cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic
      protein expression was determined by immunohistochemistry and Western blot
      analysis. RESULTS: A statistically significant difference was found in both
      adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00).
      However, changes in binding activity were not homogenous with approximately 50%
      of the tumors showing a clear increase in the binding activity, 30% displaying a
      modest increase and 15% showing a decrease of the activity. Tumors, with
      increased DNA-binding activity, also showed a statistically significant increase
      in Ku70 and Ku86 nuclear expression, as determined by Western blot and
      immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found
      in pathological samples, but not in normal tissues either from tumor patients or
      from healthy subjects. CONCLUSION: Overall, our DNA-binding activity and protein
      level are consistent with a substantial activation of the NHEJ pathway in
      colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal
      activation can result in chromosomal instability and ultimately lead to
      tumorigenesis.

PMID- 16425369
TI  - Correlation and prognostic significance of beta-galactoside alpha-2,6
      sialyltransferase and serum monosialylated alpha-fetoprotein in hepatocellular
      carcinoma.
AB  - AIM: To investigate the correlation between tissue ST6Gal I and serum msAFP in
      HCC patients, and to investigate their prognostic significance. METHODS:
      Preoperative sera, paired tumorous and non-tumorous tissues were collected from
      19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I
      activities in the tissues were measured by an in vitro microsomal enzyme activity
      assay. The percentages of tumor-specific msAFP in the sera were also estimated by
      an isoelectric focusing-immunoblotting assay. RESULTS: The tumor ST6Gal I
      activity was negatively correlated with serum msAFP percentage (r = -0.53, P =
      0.019). Both decreased tumor ST6Gal I activity and increased serum msAFP
      percentage were associated with poor tumor cell differentiation. Univariate
      analyses showed that both decreased tumor ST6Gal I activity (P = 0.028),
      increased serum msAFP percentage (P = 0.034) and poor tumor cell differentiation
      (P = 0.031) were associated with shorter overall survival. Multivariate analysis
      using the Cox regression model showed that the preoperative serum msAFP
      percentage (P = 0.022) and tumor cell differentiation status (P = 0.048) were
      independent prognostic indicators for patient overall survival. CONCLUSION: Our
      results indicate that the presence of msAFP in blood circulation is associated
      with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and
      serum msAFP are potential prognostic markers for patients with operable HCC.

PMID- 16425371
TI  - Hepatitis E virus chimeric DNA vaccine elicits immunologic response in mice.
AB  - AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3
      chimeric gene and to assess its ability to elicit specific immunologic response
      in mice. METHODS: The gene encoding the structural protein of HEV ORF2 fragment
      and full-length ORF3 was amplified by PCR. The PCR products were cloned into an
      eucaryotic expression plasmid pcDNA3. The resulting plasmid pcHEV23 was used as a
      DNA vaccine to inoculate BALB/c mice intramuscularly thrice at a dose of 100 or
      200 microg. Mice injected with empty pcDNA3 DNA or saline served as control and
      then specific immune responses in the mice were detected. RESULTS: After 2-3
      times of inoculation, all mice injected with pcHEV23 had anti-HEV IgG
      seroconversion and specific T lymphocyte proliferation. The lymphocyte
      stimulation index in the group immunized with pcHEV23 (3.1+/-0.49) was higher
      than that in the control group (0.787+/-0.12, P<0.01). None in the control group
      had a detectable level of anti-HEV IgG. CONCLUSION: DNA vaccine containing HEV
      ORF2 and ORF3 chimeric gene can successfully induce specific humoral and cellular
      immune response in mice.

PMID- 16425370
TI  - Cysteamine increases expression and activity of H+-K+-ATPase of gastric mucosal
      cells in weaning piglets.
AB  - AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on
      expression and activity of H(+)-K(+)-ATPase of gastric mucosal cells in weaning
      piglets. METHODS: Eighteen litters of newborn Xinhuai piglets were employed in
      the in vivo experiment and allocated to control and treatment groups. From 12 d
      of age (D12), piglets in control group were fed basal diet, while the treatment
      group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on
      D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28
      (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h,
      one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was
      performed to determine the levels of H(+)-K(+)-ATPase mRNA in gastric mucosa.
      H(+)-K(+)-ATPase activity in gastric mucosa homogenate was also determined.
      Gastric mucosal epithelial cells from piglets through primary cultures were used
      to further elucidate the effect of CS on expression and activity of H(+)-K(+)
      ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS
      (n = 4), respectively. The mRNA expression of H(+)-K(+)-ATPase and somatostatin
      (SS) as well as the H(+)-K(+)-ATPase activity were determined. RESULTS: in vivo,
      both mRNA expression and activity of H(+)-K(+)-ATPase in gastric mucosa of
      control group exhibited a trend to increase from D28 to D45, reaching a peak on
      D45, but did not show significant age differences. Furthermore, neither the mRNA
      expression nor the activity of H(+)-K(+)-ATPase was affected significantly by
      weaning. CS increased the mRNA expression of H(+)-K(+)-ATPase by 73%, 53%, 30%
      and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046),
      respectively. In accordance with the mRNA expression, H(+)-K(+)-ATPase activities
      were significantly higher in treatment group than in control group on D35 (P =
      0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA
      expression and activity of H+-K+-ATPase. Both H(+)-K(+)-ATPase mRNA expression
      and activity in gastric mucosal epithelial cells were significantly elevated
      after 20 h of exposure to the moderate (H(+)-K(+)-ATPase expression: P=0.03; H(+)
      K(+)-ATPase activity: P = 0.014) and high concentrations (H(+)-K(+)-ATPase
      expression: P=0.017; H(+)-K(+)-ATPase activity: P = 0.022) of CS. Significant
      increases in SS mRNA expression were observed to accompany the elevation of H(+)
      K(+)-ATPase expression and activity induced by the moderate (P = 0.024) and high
      concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects
      either on expression and activity of H(+)-K(+)-ATPase or on SS mRNA expression in
      cultured gastric mucosal epithelial cells. CONCLUSION: No significant changes are
      observed in mRNA expression and activity of H(+)-K(+)-ATPase in gastric mucosa of
      piglets around weaning from D28 to D45. CS increases expression and activity of
      gastric H(+)-K(+)-ATPase in vivo and in vivo. SS is involved in mediating the
      effect of CS on gastric H(+)-K(+)-ATPase expression and activity in weaning
      piglets.

PMID- 16425372
TI  - Relation of overexpression of S phase kinase-associated protein 2 with reduced
      expression of p27 and PTEN in human gastric carcinoma.
AB  - AIM: To investigate the significance of S phase kinase-associated protein 2
      (Skp2) expression in human gastric carcinoma and the relation between expressions
      of Skp2, p27 and PTEN. METHODS: Immunohistochemical analysis was performed on 138
      gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired
      lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30
      intestinal metaplasia specimens, 10 chronic superficial gastritis specimens and 5
      normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma
      specimens for p27 and PTEN expression. RESULTS: Skp2 labeling frequency was
      significantly higher in intestinal metaplasia (12.68+/-0.86) and adjacent mucosa
      (19.32+/-1.22) than in normal gastric mucosa (0.53+/-0.13) and chronic
      superficial gastritis (0.47+/-0.19) (P = 0.000); in dysplasia (16.74+/-0.82) than
      in intestinal metaplasia (P = 0.000); in gastric primary carcinoma (31.34+/-2.17)
      than in dysplasia and adjacent mucosa (P = 0.000); in metastasis gastric
      carcinoma in lymph nodes (39.76+/-2.00) than in primary gastric carcinoma (P =
      0.037), respectively. Skp2 labeling frequency was positively associated with
      differentiation degree (rho = 0.315, P = 0.000), vessel invasion (rho = 0.303, P
      = 0.000) and lymph node metastasis (rho = 0.254, P = 0.000) of gastric cancer.
      Expression of Skp2 was negatively associated with p27 (rho = -0.451, P = 0.000)
      and PTEN (rho = -0.480, P = 0.000) expression in gastric carcinoma. p27
      expression was positively associated with PTEN expression in gastric carcinoma
      (rho = 0.642, P = 0.000). CONCLUSION: Skp2 overexpression may be involved in
      carcinogenesis and progression of human gastric carcinoma in vivo, possibly via
      p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating
      Skp2 expression.

PMID- 16425373
TI  - Regression of hepatocellular carcinoma during vitamin K administration.
AB  - An 85-year-old man with HCV infection and diabetes mellitus was diagnosed as
      having hepatocellular carcinoma (HCC, 13 cm in diameter) based on high serum
      alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin levels as well
      as typical enhancement pattern on contrast-enhanced CT. The patient did not
      receive any interventional treatments because of advanced age and the advanced
      stage of HCC. He chose to take vitamin K, which was reported to suppress the
      growth of HCC in vitro. Three months after starting vitamin K, all three tumor
      markers were normalized and HCC was markedly regressed, showing no enhancement in
      the early arterial phase on CT. Here we present the report describing the
      regression of HCC during the administration of vitamin K.

PMID- 16425374
TI  - Unicentric Castleman's disease of the pancreas with massive central
      calcification.
AB  - Unicentric Castleman's disease of the pancreas is extremely rare, with only six
      cases described in the worldwide literature. An asymptomatic case of unicentric,
      hyaline, vascular-type Castlemanos disease (UCD) localized to the tail of the
      pancreas with central calcification imitating a primary neoplasm of the pancreas
      is presented. This is the first description of endosonographic and endoscopic
      retrograde pancreatographic findings of pancreatic UCD. Additionally, computed
      tomography, histological and serologic findings are reported.

PMID- 16425375
TI  - Bile peritonitis due to intra-hepatic bile duct rupture.
AB  - Generalized biliary peritonitis is a serious intra-abdominal emergency. Most of
      them occur due to duodenal ulcer perforation and rapidly evolve into bacterial
      peritonitis due to contamination by gut organisms and food. In this situation,
      recognition of the pathology and its treatment is straightforward and is usually
      associated with a good outcome. There are a few unusual causes of biliary
      peritonitis, of which rupture of the biliary tree is one. We describe a rare case
      of biliary peritonitis due to rupture of an intra-hepatic biliary radical.
      Unusual causes of peritonitis do interrupt our daily routine emergency surgical
      experience. Rapid recognition of the presence of peritonitis, adequate
      resuscitation, recognition of operative findings, establishment of biliary
      anatomy, and performance of a meticulous surgical procedure resulted in a good
      outcome.

PMID- 16425376
TI  - Enzyme inhibition assay for pyruvate dehydrogenase complex: clinical utility for
      the diagnosis of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is usually diagnosed by the presence of
      characteristic histopathological features of the liver and/or antimitochondrial
      antibodies (AMA) in the serum traditionally detected by immunofluorescence.
      Recently, new and more accurate serological assays for the detection of AMA, such
      as enzyme-linked immunosorbent assay (ELISA), immunoblotting, and enzyme
      inhibition assay, have been developed. Of these, the enzyme inhibition assay for
      the detection of anti- pyruvate dehydrogenase complex (PDC) antibodies offers
      certain advantages such as objectivity, rapidity, simplicity, and low cost. Since
      this assay has almost 100% specificity, it may have particular applicability in
      screening the at-risk segment of the population in developing countries.
      Moreover, this assay could be also used for monitoring the disease course in PBC.
      Almost all sera of PBC-suspected patients can be confirmed for PBC or non-PBC by
      the combination results of immunoblotting and enzyme inhibition assay without
      histopathological examination. For the development of a "complete" or "gold
      standard" diagnostic assay for PBC, similar assays of the enzyme inhibition for
      anti-2-oxoglutarate dehydrogenase complex (OGDC) and anti-branched chain oxo-acid
      dehydrogenase complex (BCOADC) antibodies will be needed in future.

PMID- 16425377
TI  - Loss of heterozygosity analyzed by single nucleotide polymorphism array in
      cancer.
AB  - Neoplastic progression is generally characterized by the accumulation of multiple
      genetic alterations including loss of tumor suppression gene function. Loss of
      heterozygosity (LOH) has been used to identify genomic regions that harbor tumor
      suppressor genes and to characterize different tumor types, pathological stages
      and progression. LOH pattern has been detected by allelotyping using restriction
      fragment length polymorphism, and later by simple sequence length polymorphisms
      (SSLPs or microsatellite) for 10 years. This paper reviews the detection of LOH
      by recently developed single nucleotide polymorphism (SNP) arrays (all analyzed
      by Affymetrix array); furthermore, its advantage and disadvantage were analyzed
      in several kinds of cancer.

PMID- 16425378
TI  - Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with
      Helicobacter pylori infection.
AB  - AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children with
      Helicobacter pylori (H pylori) infection and to evaluate their significance for
      the morphological changes found in gastric mucosa. METHODS: The study included
      106 children: 59 children (55.7%) with chronic gastritis and positive IgG against
      H pylori, 29 children (27.3%) after previous H pylori infection without the
      bacterium colonization but with positive IgG against H pylori, and 18 children
      (17%) with functional disorders of the gastrointestinal system but with normal
      IgG against H pylori. Endoscopic and histopathological evaluation of gastric
      mucosa was performed based on the Sydney System classification. The evaluation of
      sP-selectin, sICAM-1, sVCAM-1 levels in the sera of children was carried out
      using ELISA test. RESULTS: The assessment of gastritis activity degrees indicated
      statistically significant values in the antrum and corpus (P<0.001) of children
      examined. Serum sVCAM-1 levels were higher in group with gastritis due to H
      pylori infection than in group without infection and differed statistically
      (P<0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive
      molecules in infected children and decreased after eradication of H pylori. Serum
      sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were
      similar in children with and without H pylori infection. CONCLUSION: Assessment
      of adhesive molecules (sP-selectin, sICAM-1, sVCAM-1) in the sera of children
      with active H pylori infection can show the participation of sVCAM-1 in the
      pathogenesis of gastric mucosal inflammation. sP-selectin and sICAM-1
      concentrations in the sera of children with H pylori infection after eradication
      cannot reveal any significant differences as compared to healthy children.

PMID- 16425379
TI  - Concentrations of gastric mucosal cytokines in children with food allergy and
      Helicobacter pylori infection.
AB  - AIM: To measure the concentrations of chosen cytokines in the antrum mucosa
      depending on the kind of harmful pathogenic factors and to compare the
      concentrations with the values of controls without allergy and coexisting
      Helicobacter pylori (H pylori) infection. METHODS: The patients (97 children)
      were divided into three groups according to the data obtained from the case
      history, to the main cause of the disease and to the dominant clinical symptoms.
      Group I: children with food allergy (Fa); group II: children infected with H
      pylori; group III (control group): children with functional disorders of the
      alimentary tract (without Fa and Hp infection). H pylori infection was determined
      by the presence of anti-Hp antibodies in serum (ELISA method) and urease test
      performed during endoscopic examination. Cytokine concentration in homogenates of
      gastric mucosa was detected by ELISA method. RESULTS: The IL-2 concentration in
      gastric mucosa bioptates was the highest in children with Hp infection (116.5+/
      179.5 pg/mg of the protein) and Fa and Hp infection (98.1+/-101.0 pg/mg), while
      decreased in children with Fa (44.8+/-50.3 pg/mg) and controls (45.7+/-23.5
      pg/mg). The lowest mean concentration of IFN-gamma was observed in children with
      Hp infection (18.9+/-16.4 pg/mg), with Fa and Hp infection (25.5+/-27.7 pg/mg),
      with Fa (40.6+/-39.7 pg/mg) and controls (49.9+/-33.4 pg/mg). The highest IL-4
      concentrations were observed in children with Hp infection (35.3+/-52.8 pg/mg)
      and in children with Fa and Hp infection (37.2+/-51.7 pg/mg), while lower IL-4
      concentration (23.6+/-35.8 pg/mg) was found in children with Fa compared to the
      controls (22.7+/-13.8 pg/mg). The analysis of IL-4 concentrations in children
      with Hp infection regarding the intensity of gastritis showed the highest value
      (62.2+/-61.2 pg/mg) in mild and moderate gastritis. The concentrations of IL-5 in
      the gastric mucosa of children with or without Fa did not differ significantly
      and were comparable to the control group. The highest mean IL-8 value was
      observed in Hp-infected children with or without Fa. The highest concentration of
      mucosal IL-10 was detected in children with Hp infection (79.3+/-41.2 pg/mg) and
      decreased in children with Fa and Hp infection (50.1+/-18.8 pg/mg) and in
      children with Fa (39.9+/-35.5 pg/mg). The intensity and activity of the
      inflammation did not affect IL-10 concentrations in the gastric mucosa. In
      children with Hp infection, TNF-alpha concentration was the highest (45.9+/-49.3
      pg/mg) and in children with Fa and Hp infection was low (45.3+/-32.6 pg/mg),
      whereas decreased in children with Fa (21.7+/-34.2 pg/mg) and in controls (31.6+/
      14.5 pg/mg). CONCLUSION: The morphological changes of the gastric mucosa in
      children with Hp infection are comparable to those in children with Fa and
      coexisting Hp infection. Cytokine concentration in children with Fa and Hp
      infection is significantly different in IFN-gamma, IL-2, IL-8, and TNF-alpha.

PMID- 16425380
TI  - Effect of bombesin and neurotensin on gut barrier function in partially
      hepatectomized rats.
AB  - AIM: To investigate the effect of regulatory peptides bombesin (BBS) and
      neurotensin (NT) on intestinal barrier function in partially hepatectomized rats.
      METHODS: Ninety male Wistar rats were randomly divided into five groups: I (n=0):
      controls, II (n= 20): sham operated, III (n=20): partial hepatectomy 70% (PHx),
      IV (n=20): PHx+BBS (30 microg/kg/d), V (n=20): PHx+NT (300 microg/kg/d). Groups
      IV and V were treated for 8 days before PHx and 48 h post surgery. At the end of
      the experiment, on day 10, intestinal barrier function was assessed by measuring
      endotoxin concentrations in portal and aortic blood. Tissue sections of the
      terminal ileum were examined histologically and villus density, mucosal
      thickness, mitotic activity and apoptosis in crypts were assessed. In addition,
      ileal mucosa was analyzed for DNA and protein content and microbiological
      analysis was performed in cecal contents. To estimate intestinal oxidative
      stress, lipid peroxidation was determined on tissue homogenates from terminal
      ileum. RESULTS: BBS or NT administration significantly reduced portal and
      systemic endotoxemia observed 48 h after partial hepatectomy. In hepatectomized
      rats (group III), a trend towards induction of mucosal atrophy was observed,
      demonstrated by the reduction of villus density, mucosal thickness, protein
      content and significant reduction of DNA, while these alterations were reversed
      by regulatory peptides administration. This trophic effect of BBS and NT was
      accompanied by induction of mitoses above control levels and a significant
      reduction of apoptosis in intestinal crypts. Intestinal lipid peroxidation was
      found significantly lower in PHx group and regulatory peptides exerted an
      antioxidant action, further decreasing this parameter of oxidative stress. The
      bacterial population of E. coli and aerobic Gram (+) cocci was increased in cecal
      content of hepatectomized rats, while this parameter was not affected by the
      administration of BBS or NT. CONCLUSION: Gut regulatory peptides BBS and NT
      improve intestinal barrier function and reduce endotoxemia in experimental
      partial hepatectomy. This effect is, at least in part, mediated by their trophic,
      anti-apoptotic, mitogenic, and antioxidant effect on the intestinal epithelium.
      This observation might be of potential value in patients undergoing liver
      resection.

PMID- 16425381
TI  - Expression of Ki-67, p53, and K-ras in chronic pancreatitis and pancreatic ductal
      adenocarcinoma.
AB  - AIM: To examine surgical specimens of pancreas with either chronic pancreatitis
      or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia
      in pancreas represent precursor lesions for pancreatic cancer. METHODS: We
      examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of
      pancreas with adenocarcinomas (n=11) and chronic pancreatitis (n=12). Cellular
      proliferation was assessed by Ki-67 proliferation index using the proliferation
      marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium
      into normal (n=7), ductal hyperplasia (n=3), dysplasia (n=4), and cancerous
      lesion (n=11) after hematoxylin and eosin staining, Ki-67, and CEA
      immunohistochemical staining. In cases with chronic pancreatitis, the specimen
      was pathologically examined as in cases with pancreas cancer, and they were also
      determined as normal (n=10), ductal hyperplasia (n=4), or dysplasia (n=5). p53
      and K-ras expression were also studied by immunohistochemical staining. RESULTS:
      In pancreatic cancer, the Ki-67 index was 3.73+/-3.58 in normal site, 6.62+/-4.39
      in ductal hyperplasia, 13.47+/-4.02 in dysplasia and 37.03+/-10.05 in cancer
      tissue, respectively. Overall, p53 was positive in normal ducts, ductal
      hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7 (0%), 7 of 9
      (78%), and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1
      of 3 (33%), 4 of 6 (67%), 4 of 5 (80%), respectively. CONCLUSION: Our results
      favorably support the hypothesis that ductal hyperplasia and dysplasia of the
      pancreas might be precursor lesions for pancreas cancer. Further evaluation of
      oncogenes by the molecular study is needed.

PMID- 16425382
TI  - Effect of IL-4 on altered expression of complement activation regulators in rat
      pancreatic cells during severe acute pancreatitis.
AB  - AIM: To investigate the effect of IL-4 on the altered expression of complement
      activation regulators in pancreas and pancreatic necrosis during experimental
      severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by
      retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic
      duct. We immunohistochemically assayed the expression of three complement
      activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous
      restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in
      the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction
      of SAP model. Meanwhile the levels of amylase and lipase were determined, and
      morphological examination was performed. Then, 61 rats were randomly divided into
      three groups. Group A (n=21) received no treatment after the SAP model was
      established; group B (n=20) was given IL-4 (8 microg/animal) intraperitoneally
      0.5 h before the SAP model was established; group C (n=20) was given IL-4 (8
      microg/animal) intraperitoneally 0.5 h after the SAP model was established.
      Plasma amylase and lipase, extent of pancreatic necrosis and expression of
      complement activation regulators were investigated 6 h after the induction of SAP
      model. RESULTS: Three complement activation regulators were all expressed in
      pancreatic acinar cells. MCP was not found on the basolateral surface as
      reported. Contrary to the gradually increasing plasma level of amylase and
      lipase, expression of complement activation regulators decreased after SAP model
      was set up. At the same time, the severity of pancreatic necrosis was enhanced. A
      strong negative correlation was found between the expression of MCP, DAF, CD59 in
      pancreatic acinar cells and the severity of pancreatic necrosis (r= -0.748, 
      0.827, -0.723; P<0.01). In the second series of experiments, no matter when the
      treatment of IL-4 was given (before or after the induction of SAP model), the
      serum level of amylase or lipase was decreased and the extent of pancreatic
      necrosis was ameliorated significantly. Compared to SAP control group, the
      expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before
      the induction of SAP model (P<0.01, P<0.05), but the expression of MCP was not
      influenced (P>0.05). The expression of DAF was enhanced, when IL-4 was given
      after the induction of SAP model (P<0.05), but the expression of CD59 and MCP did
      not change (P>0.05). CONCLUSION: Complement activation regulators may participate
      in the pathogenesis of pancreatic inflammation. Downregulation of complement
      activation regulators expression may be one of the causes of pancreatic necrosis.
      IL-4 treatment may control SAP aggravation by enhancing expression of DAF and
      CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may
      play an important role in the regulation of complement activation regulators
      during SAP.

PMID- 16425383
TI  - Effects of nuclear factor-kappaB on rat hepatocyte regeneration and apoptosis
      after 70% portal branch ligation.
AB  - AIM: To detect the DNA binding activity of nuclear factor-kappaB (NF-kappaB) in
      rat hepatocyte and to investigate the effects of NF-kappaB on rat hepatocyte
      regeneration and apoptosis after 70% portal branch ligation. METHODS: Sixty
      Wistar rats were randomly divided into control group and portal branch ligation
      group. The animals were killed 12 h, 1, 2, 3, 7, and 14 d after surgery to
      determine the contents of plasma ALT. Hepatocytes were isolated and nuclear
      protein was extracted. DNA binding activity of NF-kappaB was measured by EMSA.
      Hepatocyte regeneration and apoptosis were observed under microscope by TUNEL
      staining. The ultrastructural changes of liver were observed under electron
      microscope. RESULTS: Seventy percent portal branch ligation produced atrophy of
      the ligated lobes and the perfused lobes underwent compensatory regeneration, the
      total liver weight and plasma ALT levels were maintained at the level of sham
      operated animals throughout the experiment. After 2 d of portal branch ligation,
      DNA binding activity of NF-kappaB in hepatocyte increased and reached its peak,
      the number of apoptotic hepatocyte in the ligated lobes and the number of mitotic
      hepatocyte in the perfused lobes also reached their peak. Typical apoptotic
      changes and evident fibrotic changes in the ligated lobes were observed under
      electron microscope. CONCLUSION: After 70% portal branch ligation, DNA binding
      activity of NF-kappaB in hepatocyte is significantly increased and NF-kappaB
      plays an important role in hepatocyte regeneration and apoptosis.

PMID- 16425384
TI  - Effects of different ingredients of zedoary on gene expression of HSC-T6 cells.
AB  - AIM: To investigate the effects of four different ingredients of zedoary (Curcuma
      aromatica oil, Curcumol, beta-elemence, and Curcumin) on the gene expressions of
      hepatic stellate cells (HSCs), and to explore the molecular mechanism of zedoary
      against hepatic fibrosis at gene network level. METHODS: We detected the mRNA
      sequences of 50 liver fibrosis-related genes in GenBank and designed
      oligonucleotide probes. We synthesized oligonucleotides with PE8909 DNA
      synthesizing instrument, and carried out oligonucleotide microarray with OGR-04
      dropping instrument and aldehyded glass chip. Cultured HSC-T6 cells were treated
      with different concentrations of Colchicine, Curcuma aromatica oil, Curcumol,
      beta-elemence, and Curcumin. According to the experiment of cell toxicity, we
      took the appropriate concentrations of medicines that resulted in over 50% of
      cell survival as experiment concentrations. We collected the cells at 1, 6, 12,
      and 24 h, and extracted total RNA with TRIzol reagent, then labeled cDNAs with
      Cy3-dUTP and Cy5-dUTP. These labeled cDNAs were hybridized to an oligonucleotide
      microarray which was washed several times and scanned by scanner GenePix 4000B.
      Different gene expressions of HSC-T6 cells were analyzed by ImaGene 4.2 software.
      RESULTS: After HSC-T6 cells were cultured in a medium containing 6.25 microg/mL
      Colchicine for 12 h, expression of TIMP-1 decreased 2.2-folds. After HSC-T6 cells
      were cultured in a medium containing 78.125 microg/mL of Curcuma aromatica oil
      for 24 h, the expression of TIMP-2 and IL-6 decreased 2.3- and 2.2-folds,
      respectively. Moreover, after HSC-T6 cells were cultured in a medium containing
      1.5625 microg/mL of Curcumol for 12 h, the expression of TGFbeta1 and P450a
      decreased 2.3- and 2.1-folds, respectively. CONCLUSION: Our results may show the
      possible molecular mechanism of Curcuma aromatica oil and Curcumol against
      hepatic fibrosis.

PMID- 16425385
TI  - Changes of duplex parameters and splenic size in liver transplant recipients
      during a long period of observation.
AB  - AIM: To assess the changes of portal and arterial velocities, resistance index,
      spleen and liver size during a long observation period (13.7 years) after
      orthotopic liver transplantation (OLT). METHODS: Two hundred and sixty patients
      were recruited retrospectively for this study and divided into groups with
      defined time intervals after OLT. The cross-sectional changes of portal and
      arterial velocities, resistance index, spleen and liver size between the defined
      time intervals were studied. The complications detected by ultrasound were
      compared to gold standard methods. RESULTS: The mean values for liver size were
      all within the normal range. The splenic size decreased between the time
      intervals 100 and 1,000 d after OLT (t; P<0.01). While portal and arterial flow
      velocities decreased up to 5.5 years (t; portal velocity P<0.01, maximal systolic
      velocity P=0.05, maximal end diastolic velocity P<0.01), RI increased during this
      interval (t: P<0.01). Higher RI values were found in older patients (r=0.24,
      P<0.001). CONCLUSION: The arterial and portal velocities show adaptation
      processes continuing over the course of many years after OLT and are reported for
      the first time. The vascular complications detected by ultrasound occur mostly up
      to 100 d after OLT.

PMID- 16425386
TI  - Improvement of regional cerebral blood flow after oral intake of branched-chain
      amino acids in patients with cirrhosis.
AB  - AIM: To evaluate the effect of oral intake of branched-chain amino acids (BCAA)
      on brain perfusion in patients with liver cirrhosis. METHODS: Single photon
      emission computed tomography scans were performed in 43 patients with cirrhosis
      and in 15 age-matched healthy subjects. Twenty-nine out of forty-three patients
      were randomly treated with either BCAA granules or placebo, and single photon
      emission computed tomography was performed before and after the treatment. We
      measured the regional cerebral blood flow values using a three-dimensional
      stereotaxic region of interest template. RESULTS: Cirrhotic patients had regions
      of significant hypoperfusion in the bilateral central (right P=0.039, P<0.05;
      left P=0.006 P<0.01), parietal (right P=0.018, P<0.05; left P=0.009, P<0.01),
      angular (right P=0.039, P<0.05; left P 0.008, P<0.01), and left pericallosal
      segments (P=0.038 P<0.05) as compared with healthy subjects. A significant
      increase in cerebral perfusion was observed 70 min after the oral intake of BCAA
      in the angular (right P=0.012, P<0.05; left P=0.049, P<0.05), temporal (right
      P=0.012, P<0.05; left P=0.038, P<0.05), pericallosal segments (right P=0.025,
      P<0.05; left P=0.049, P<0.05) and left precentral (P=0.044, P<0.05), parietal
      (P=0.040, P<0.05) and thalamus (P=0.033, P<0.05). No significant change in
      perfusion was observed in the placebo group. CONCLUSION: Administration of BCAA
      rapidly improves cerebral perfusion.

PMID- 16425387
TI  - Pregnancy is not a risk factor for gallstone disease: results of a randomly
      selected population sample.
AB  - AIM: To investigate the prevalence, risk factors, and selection of the study
      population for cholecystolithiasis in an urban population in Germany, in relation
      to our own findings and to the results in the international literature. METHODS:
      A total of 2 147 persons (1,111 females, age 42.8+/-12.7 years; 1,036 males, age
      42.3+/-13.1 years) participating in an investigation on the prevalence of
      Echinococcus multilocularis were studied for risk factors and prevalence of
      gallbladder stone disease. Risk factors were assessed by means of a standardized
      interview and calculation of body mass index (BMI). A diagnostic ultrasound
      examination of the gallbladder was performed. Data were analyzed by multiple
      logistic regression, using the SAS statistical software package. RESULTS:
      Gallbladder stones were detected in 171 study participants (8.0%, n=2,147). Risk
      factors for the development of gallbladder stone disease included age, sex, BMI,
      and positive family history. In a separate analysis of female study participants,
      pregnancy (yes/no) and number of pregnancies did not exert any influence.
      CONCLUSION: Findings of the present study confirm that age, female sex, BMI, and
      positive family history are risk factors for the development of gallbladder stone
      disease. Pregnancy and the number of pregnancies, however, could not be shown to
      be risk factors. There seem to be no differences in the respective prevalence for
      gallbladder stone disease in urban and rural populations.

PMID- 16425388
TI  - Characteristics of patients with columnar-lined Barrett's esophagus and risk
      factors for progression to esophageal adenocarcinoma.
AB  - AIM: To determine the risk factors for the development of esophageal
      adenocarcinoma in these patients with columnar-lined esophagus (CLE). METHODS:
      Data collected retrospectively on 597 consecutive patients diagnosed at endoscopy
      and histology to have CLE at Leeds General Infirmary between 1984 and 1995 were
      analyzed. Factors evaluated included age, sex, length of columnar segment,
      smoking, and drinking habits, history of non-steroidal ingestion, presence of
      endoscopic esophagitis, ulceration or benign strictures and presence of
      Helicobacter pylori in esophageal biopsies. Univariate and multivariate analyses
      were performed to identify risk factors for the development of adenocarcinoma.
      RESULTS: Forty-four patients presented or developed esophageal adenocarcinoma
      during follow-up. Independent risk factors for the development of adenocarcinoma
      in patients with CLE were males (OR 5.12, 95%CI 2.04-12.84, P=0.0005), and benign
      esophageal stricture (OR 4.37, 95%CI 2.02-9.45, P=0.0002). Male subjects and
      patients who developed benign esophageal stricture constituted 86% (n=38) of all
      patients who presented or developed esophageal adenocarcinoma. The presence of
      esophagitis was associated with a significant reduction in the development of
      esophageal carcinoma (OR 0.28, 95%CI 0.13-0.57, P=0.0006). No other clinical
      characteristics differentiate between the non-malignant and malignant group.
      CONCLUSION: In patients with CLE, endoscopic surveillance for the early detection
      of adenocarcinoma may be restricted to male subjects, as well as patients who
      develop benign esophageal strictures.

PMID- 16425389
TI  - Association between cag-pathogenicity island in Helicobacter pylori isolates from
      peptic ulcer, gastric carcinoma, and non-ulcer dyspepsia subjects with
      histological changes.
AB  - AIM: To investigate the presence of the cag-pathogenicity island and the
      associated histological damage caused by strains with complete cag-PAI and with
      partial deletions in correlation to the disease status. METHODS: We analyzed the
      complete cag-PAI of 174 representative Helicobacter pylori (H pylori ) clinical
      isolates obtained from patients with duodenal ulcer, gastric ulcer, gastric
      cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz
      cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2 spanning five different
      loci of the whole cag-PAI by polymerase chain reaction (PCR). RESULTS: The
      complete screening of the genes comprising the cag-PAI showed that larger
      proportions of subjects with gastric ulcer (97.8%) inhabited strains with
      complete cag-PAI, followed by gastric cancer (85.7%), non-ulcer dyspepsia (7.1%),
      and duodenal ulcer (6.9%), significant differences were found in the percentage
      distribution of the genes in all the clinical groups studied. It was found that
      strains with complete cag-PAI were able to cause severe histological damage than
      with the partially deleted ones. CONCLUSION: The cag-PAI is a strong virulent
      marker in the disease pathogenesis as it is shown that a large number of those
      infected with strain with complete cag-PAI had one or the other of the
      irreversible gastric pathologies and interestingly 18.5% of them developed
      gastric carcinoma. The presence of an intact cag-PAI correlates with the
      development of more severe pathology, and such strains were found more frequently
      in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI
      appear to be sufficient to render the organism less pathogenic.

PMID- 16425390
TI  - Single daily amikacin versus cefotaxime in the short-course treatment of
      spontaneous bacterial peritonitis in cirrhotics.
AB  - AIM: To compare the efficacy and safety of single daily amikacin vs. cefotaxime
      in the 5-d treatment of spontaneous bacterial peritonitis (SBP). METHODS: Thirty
      seven cirrhotic patients with SBP, 19 in group A and 18 in group B, were studied.
      Group A received 1 g of cefotaxime every 6 h, and group B received 500 mg of
      amikacin qd. Both antibiotics were administered up to 5 d and the responses were
      compared. RESULTS: Infection was cured in 15 of 19 patients (78.9%) treated with
      cefotaxime and in 11 of 18 (61.1%) treated with amikacin. Four patients of the
      Cefotaxime group (21.1%) and five patients of the Amikacin group (27.8%) died.
      Two in each group (10.5% vs 11.1%) had renal impairment during study period. One
      in each group (5.3% vs 5.6%) may be considered to suffer from nephrotoxicity due
      to increased urinary beta(2)-microglobulin concentration. CONCLUSION: In this
      study, single daily doses of amikacin in the treatment of SBP in cirrhotics were
      not associated with an increased incidence of renal impairment or nephrotoxicity.
      However, a 5-d regimen of amikacin is less effective than a 5-d regimen of
      cefotaxime in the SBP treatment.

PMID- 16425391
TI  - Scattered and rapid intrahepatic recurrences after radio frequency ablation for
      hepatocellular carcinoma.
AB  - AIM: To evaluate a series of patients with hepatocellular carcinoma (HCC) treated
      with several different protocols and devices. METHODS: We treated 138 patients
      [chronic hepatitis/liver cirrhosis (Child-Pugh A/B/C), 3/135 (107/25/3)] with two
      different devices and protocols: cool-tip needle [initial ablation at 60 W
      (standard method) (n=37) or at 40 W (modified method) (n=28)] or; ablation with a
      LeVeen needle using a standard single-step, full expansion (single-step) method
      (n=39) or a multi-step, incremental expansion (multi-step) method. RESULTS:
      Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the
      ablation. Nine patients were treated by the cool-tip original protocol (60 W)
      (9/37=24%) and the other two by the LeVeen single-step method (2/39=5%). The
      location of the recurrence was surrounding and limited to the site of ablation
      segment in three cases, and spread over one lobule or both lobules in the other
      eight cases. There was no recurrence in the patients treated with the modified
      cool-tip modified method (40 W) or the LeVeen multi-step method. CONCLUSION:
      There is a risk of rapid and scattered recurrence after RFA, especially when the
      standard cool-tip procedure is used. Because such recurrence would worsen the
      prognosis, we recommend that modified protocols for the cool-tip and LeVeen
      needle methods should be used in clinical practice.

PMID- 16425392
TI  - Effect of pegylated interferon alpha 2b plus ribavirin treatment on plasma
      transforming growth factor-beta1, metalloproteinase-1, and tissue
      metalloproteinase inhibitor-1 in patients with chronic hepatitis C.
AB  - AIM: To evaluate the effect of antiviral treatment on plasma levels of
      transforming growth factor-beta1 (TGF-beta1), metalloproteinase 1 (MMP-1), and
      tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with chronic
      hepatitis C. METHODS: TGF-beta1, MMP-1, and TIMP-1 plasma concentrations were
      measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with
      pegylated interferon-alpha 2b (PEG-IFN-alpha2b) plus ribavirin (RBV) and after 24
      wk of follow-up. Patients were divided into two groups: responders (R) and non
      responders (NR) related to achieved sustained virologic response. Normal values
      were evaluated in plasma samples of 13 healthy volunteers. RESULTS: Baseline
      plasma concentrations of TGF-beta1 and TIMP-1 (30.9+/-3.7 and 1 506+/-61 ng/mL
      respectively) measured in all subjects significantly exceeded the normal values
      (TGF-beta1: 18.3+/-1.6 ng/mL and TIMP-1: 1 102+/-67 ng/mL). In contrast,
      pretreatment MMP-1 mean level (6.5+/-0.9 ng/mL) was significantly lower than
      normal values (11.9+/-0.9 ng/mL). Response to the treatment was observed in 12
      patients (43%). TGF-beta1 mean concentration measured during the treatment phase
      decreased to the control level in both groups. However at wk 72, values of NR
      patients increased and became significantly higher than in R group. TIMP-1
      concentrations in R group decreased during the treatment to the level similar to
      normal. In NR group, TIMP-1 remained significantly elevated during treatment and
      follow-up phase and significant difference between both groups was demonstrated
      at wk 48 and 72. MMP-1 levels were significantly decreased in both groups at
      baseline. Treatment caused rise of its concentration only in the R group, whereas
      values in NR group remained on the level similar to baseline. Statistically
      significant difference between groups was noted at wk 48 and 72. CONCLUSION:
      These findings support the usefulness of TGF-beta1, TIMP-1, and MMP-1 in the
      management of chronic hepatitis C. Elevated TIMP-1 and low MMP-1 plasma
      concentrations during antiviral therapy may indicate medication failure.

PMID- 16425393
TI  - Prevalence and risk factors of stress-induced gastrointestinal bleeding in
      critically ill children.
AB  - AIM: To assess the frequency and the risk factors of stress-induced
      gastrointestinal (GI) bleeding in children admitted to a pediatric intensive care
      unit (PICU). METHODS: The medical records of children aged between 1 month and 15
      years admitted to the PICU between January 2002 and December 2002 were reviewed.
      Demographic data, indications for PICU admission, principle diagnosis, and basic
      laboratory investigations were recorded. Previously described factors for stress
      ulcer bleeding (mechanical ventilation, sepsis, acute respiratory distress
      syndrome, renal insufficiency, coagulopathy, thrombocytopenia, and intracranial
      pathology) were used as independent variables in a multivariate analysis.
      RESULTS: One hundred and seventy of two hundred and five medical records were
      eligible for review. The most common indication for PICU admission was
      respiratory failure (48.8%). Twenty-five children received stress ulcer bleeding
      prophylaxis with ranitidine. The incidence of stress ulcer bleeding was 43.5%, in
      which 5.3% were clinically significant bleeding. Only mechanical ventilation and
      thrombocytopenia were significantly associated with stress ulcer bleeding using
      the univariate analysis. The odds ratio and 95% confidence intervals were 5.13
      (1.86-14.12) and 2.26 (1.07-4.74), respectively. However, the logistic regression
      analysis showed that mechanical ventilation was the only significant risk factor
      with the odds ratio of 14.1. CONCLUSION: The incidence of gastrointestinal
      bleeding was high in critically ill children. Mechanical ventilation was an
      important risk factor for gastrointestinal bleeding.

PMID- 16425394
TI  - Favorable response to subcutaneous administration of infliximab in rats with
      experimental colitis.
AB  - AIM: To investigate the influence of infliximab (Remicade) on experimental
      colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats. METHODS:
      Thirty-six Wistar rats were allocated into four groups (three groups of six
      animals each and a fourth of 12 animals). Six more healthy animals served as
      normal controls (Group 5). Group 1: colitis was induced by intracolonic
      installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab
      was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was
      induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW;
      Group 3: colitis was induced and infliximab was subcutaneously administered at a
      dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with
      infliximab. Infliximab was administered on d 2-6. On the 7(th) d, all animals
      were killed. The colon was fixed in 10% buffered formalin and examined by light
      microscopy for the presence and activity of colitis and the extent of tissue
      damage. Tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) were
      also measured. RESULTS: Significant differences concerning the presence of
      reparable lesions and the extent of bowel mucosa without active inflammation in
      all groups of animals treated with infliximab compared with controls were found.
      Significant reduction of the tissue levels of TNF-alpha in all groups of treated
      animals as compared with the untreated ones was found (0.47+/-0.44, 1.09+/-0.86,
      0.43+/-0.31 vs 18.73+/-10.53 respectively). Significant reduction in the tissue
      levels of MDA was noticed in group 1 as compared to group 4, as well as between
      groups 2 and 4. CONCLUSION: Subcutaneous administration of infliximab reduces the
      inflammatory activity as well as tissue TNF-alpha and MDA levels in chemical
      colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological
      results and produces higher reduction of the levels of TNF-alpha than at a dose
      of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of
      tissue MDA levels than at a dose of 15 mg/kg BW.

PMID- 16425395
TI  - Relative predictive factors for hepatocellular carcinoma after HBeAg
      seroconversion in HBV infection.
AB  - AIM: To determine the predictive factors for hepatocellular carcinoma (HCC)
      development in patients after spontaneous or therapeutic HBeAg seroconversion.
      METHODS: In 48 patients who seroconverted to anti-HBe positive during follow-up,
      the background factors for HCC development were analyzed. RESULTS: HCC was
      developed in six patients during follow-up (average follow-up after HBeAg
      seroconversion: 10.9+/-5.4 years). The incidence of HCC evaluated by Kaplan-Meier
      analysis was significantly higher in patients with abnormal aspartate
      aminotransferase (AST>40 IU/L) level, lower platelet counts (PLT< 10 x
      10(4)/microL), lower albumin level (Alb<30 g/L), positive HBV-DNA or older age at
      seroconversion (>40 years). However, lower platelet count was the only predictive
      factor for HCC development shown by multivariate proportional-hazard analysis.
      CONCLUSION: Active hepatitis or advanced hepatitis at HBeAg seroconversion or
      progressive hepatitis even after HBeAg seroconversion would be the risk factors
      for HCC development. These predictive factors should be taken into account in
      determining the frequency of biochemical study or imaging studies for HCC
      surveillance.

PMID- 16425396
TI  - Evaluation of liver tissue by polymerase chain reaction for hepatitis B virus in
      patients with negative viremia.
AB  - AIM: To assess the clinical significance of Hepatitis B virus (HBV) DNA
      localization in the liver tissue of patients with positive HBsAg and negative
      viremia. METHODS: HBV virological parameters of 33 HBsAg positive chronic
      hepatitis patients, including seromarkers and HBV DNA amplification in both sera
      and liver biopsies, were evaluated. RESULTS: Ten patients had negative viremia
      and positive HBV DNA in their liver biopsies. Most of them had HBeAg
      negative/HBeAb-positive chronic hepatitis. Their liver biochemical and
      histopathological profiles were different from the viremic patients. Their
      disease pattern was designated as "hepatitis B in situ". CONCLUSION: Hepatitis B
      in situ is a consequential entity which can be missed in clinical practice. It is
      a new clinical pattern of chronic HBV infection that considers HBV in liver
      biopsy and adds a new indication for antiviral therapy.

PMID- 16425397
TI  - Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange
      in patients with portal hypertension and hepatopulmonary syndrome.
AB  - AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS)
      on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of
      hepatopulmonary syndrome ( HPS ). METHODS: Seven patients, three of them with
      advanced HPS, in whom detailed pulmonary function tests were performed before and
      after TIPS placement at the University of Alabama Hospital and at the Hospital
      Clinic, Barcelona, were considered. RESULTS: TIPS patency was confirmed by
      hemodynamic evaluation. No changes in arterial blood gases were observed in the
      overall subset of patients. Transient arterial oxygenation improvement was
      observed in only one HPS patient, early after TIPS, but this was not sustained 4
      mo later. CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange
      in patients with portal hypertension. This data does not support the use of TIPS
      as a specific treatment for HPS. However, it does reinforce the view that TIPS
      can be safely performed for the treatment of other complications of portal
      hypertension in patients with HPS.

PMID- 16425398
TI  - Incidence and localization of lymphoid follicles in early colorectal neoplasms.
AB  - AIM: To investigate the incidence and localizations of lymphoid follicles (LFs)
      in early colorectal neoplasms in human beings. METHODS: From July 1992 to
      September 1999, a total of 1,324 early colorectal neoplasms were removed
      endoscopically or surgically at our hospital; 1,031 (77.9%) were available for
      analysis in this study. Localization of LFs was defined histologically: as
      submucosal LFs, if located under the muscularis mucosa; and as intramucosal LFs,
      if located across or over the muscularis mucosa. RESULTS: Histologically, the
      materials included 903 intramucosal neoplasms and 128 submucosal cancers. Overall
      incidence of LFs was 27.2% (280/1 031). The incidence of LFs was significantly
      higher in females (33.6% vs 24.9%, P=0.0064), the right-sided colon (32.2% vs
      25.6%, P=0.0403) and in flat or depressed type lesions (34.6% vs 25.2%, P<0.0001)
      as compared to males, left-sided colon and protruding type lesions, respectively.
      The incidences of intramucosal neoplasms and submucosal cancers were 24.3% and
      43.8%, respectively (P<0.0001). Localizations of LFs (intramucosal LF/submucosal
      LF) in depressed, flat, and protruding types were 1/24, 14/36, and 131/74,
      respectively. CONCLUSION: The incidence of LFs in early human colorectal
      neoplasms significantly differs by gender, location, macroscopic type, and
      histology. Moreover, localization significantly differs by macroscopic type.

PMID- 16425399
TI  - MSX2 overexpression inhibits gemcitabine-induced caspase-3 activity in pancreatic
      cancer cells.
AB  - AIM: To evaluate the effect of MSX2 on gemcitabine-induced caspase-3 activation
      in pancreatic cancer cell line Panc-1. METHODS: Using V5-tagged MSX2 expression
      vector, stable transfectant of MSX2 was generated from Panc-1 cells (Px14 cells).
      Cell viability under gemcitabine administration was determined by MTT assay
      relative to control cell line (empty-vector transfected Panc-1 cells; P-3EV
      cells). Hoechst staining was used for the detection of apoptotic cell. Activation
      of caspase-3 was assessed using Western blotting analysis and direct measurement
      of caspase-3 specific activities. RESULTS: MSX2 overexpression in Panc-1 cells
      resulted in decreased gemcitabine-induced caspase-3 activation and increased cell
      viability under gemcitabine treatment in Px14 cells. CONCLUSION: MSX2 exerts
      repressive effects on gemcitabine-induced apoptotic pathway. This novel apoptosis
      regulating function of MSX2 may provide a new therapeutic target for pancreatic
      cancer.

PMID- 16425400
TI  - Association of Helicobacter pylori IgA antibodies with the risk of peptic ulcer
      disease and gastric cancer.
AB  - AIM: To compare the prevalence of Helicobacter pylori (H pylori) IgG and IgA
      antibodies between adult subjects, with defined gastric diseases, non-defined
      gastric disorders and those representing the population. METHODS: Data on H
      pylori IgG and IgA antibodies, determined by enzyme immunoassay, were analyzed in
      3,252 subjects with DGD including 482 patients with gastric ulcer, 882 patients
      with duodenal ulcer, 1,525 patients with chronic gastritis only and 363 subjects
      with subsequent gastric cancer, 19,145 patients with NoDg and 4,854 POPUL
      subjects. The age-adjusted prevalences were calculated for 1- and 20-year age
      cohorts. RESULTS: The prevalences of IgG antibodies were equally high (89-96%) in
      all 20-year age cohorts of the DGD groups, whereas the prevalences of IgG
      antibodies were lower and increased by age in the POPUL and NoDg groups. The
      prevalences of IgA antibodies were also higher in the DGD groups; among them CA
      (84-89%) and GU groups (78-91%) showed significantly higher prevalences than DU
      (68-77%) and CG patients (59-74%) (OR 2.49, 95%CI 1.86-3.34 between the GU and DU
      groups). In the CA, GU, and DU groups, the IgA prevalences showed only minor
      variation according to age, while they increased by age in the CG, POPUL, and
      NoDg groups (P<=0.0001). The IgA response, but not the IgG response, was
      associated with an increased risk of CA (OR 2.41, 95%CI 1.79-3.53) and GU (OR
      2.57, 95%CI 1.95-3.39) in comparison with CG patients. CONCLUSION: An IgA
      antibody response during H pylori infection is significantly more common in CA
      and GU patients as compared with CG patients.

PMID- 16425401
TI  - Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in
      relation to colorectal cancer risk and patients' survival.
AB  - AIM: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to
      colorectal cancer development and whether they are associated with
      clinicopathological variables are not well identified. METHODS: We examined the
      genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish
      population by using PCR-restriction fragment length polymorphism (RFLP). RESULTS:
      SULT1A1 *2/*2 genotype (OR=2.49, 95%CI=1.48-4.19, P=0.0002) and *2 allele
      (OR=1.56, 95%CI=1.16-2.10, P=0.002) had an effect on colorectal cancer
      susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type
      predicted a worse prognosis in the patients independently of gender, age, Dukes'
      stage, growth pattern, and differentiation (P=0.03). CONCLUSION: Polymorphism in
      SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological
      indicator of prognosis in the patients.

PMID- 16425402
TI  - Immunoproteomics of membrane proteins of Shigella flexneri 2a 2457T.
AB  - AIM: To screen the immunogenic membrane proteins of Shigella flexneri 2a 2457T.
      METHODS: The routine two-dimensional polyacrylamide gel electrophoresis (2-DE)
      and Western blotting were combined to screen immunogenic proteins of S. flexneri
      2a 2457T. Serum was gained from rabbits immunized with the same bacteria.
      Immunogenic spots were cut out from the polyacrylamide gel and digested by
      trypsin in-gel. Matrix-assisted laser desorption/ionization time of flight-mass
      spectrometry (MALDI-TOF-MS) was performed to determine the molecular weight of
      peptides. Electrospray ionization (ESI-MS/MS) was performed to determine the
      sequences of the interesting peptides. RESULTS: A total of 20 spots were
      successfully identified from Coomassie brilliant blue stained gels representing
      13 protein entries, 5 known antigens and 8 novel antigens. A hypothetical protein
      (YaeT) was detected, which might be a candidate target of vaccine. CONCLUSION:
      Membrane proteins of S. flexneri 2a 2457T were successfully observed by 2-DE.
      Several known and novel antigens were identified by mass spectrum.

PMID- 16425403
TI  - Non-parasitic splenic cysts: a report of three cases.
AB  - Primary splenic cyst is a relatively rare disease, and the majority of cases are
      classified as epithelial cysts. Three cases with nonparasitic splenic cysts are
      presented: two epithelial and one pseudocyst. All cases had an atypical
      symptomatology, consisted mainly of fullness in the left upper abdomen and a
      palpable mass. Preoperative diagnosis was established with ultrasonography and
      computerized tomography. Two cases with large cysts located in the splenic hilum
      were treated with open complete splenectomy. The most recent case, a pseudocyst,
      was managed laparoscopically with partial cystectomy. All cases did not have any
      problems or recurrence during follow-up. Laparoscopic partial cystectomy is an
      acceptable procedure for the treatment of splenic cysts, because it cures the
      disease preserving the splenic tissue. Complete splenectomy is reserved for cases
      in which cyst excision cannot be done otherwise.

PMID- 16425404
TI  - Secondary pouchitis in a post-operative patient with ulcerative colitis,
      successfully treated by salvage surgery.
AB  - We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion
      in the ileal reservoir provoked by pouch-related complication following total
      colectomy and pouch anal anastomosis, which was successfully treated by salvage
      surgery. A 20-year-old woman with ulcerative colitis developed acute severe
      bloody diarrhea following proctocolectomy, ileal pouch-anal anastomosis and
      diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly
      caused by a peripouch abscess and partly concerned with the abnormal pouch
      formation. The remnant rectum and ileal pouch were excised and ileal pouch-anal
      anastomosis and diverting ileostomy were constructed. The postoperative course
      was uneventful with no sign of pouchitis. Salvage surgery may be indicated to
      treat secondary pouchitis when caused by surgery-related complications.

PMID- 16425406
TI  - Cycling of antibiotics for the prophylaxis of recurrent spontaneous bacterial
      peritonitis in a cirrhotic patient.

PMID- 16425405
TI  - Crohn's disease and recurrent appendicitis: a case report.
AB  - The clinical diagnosis of classic Crohn's disease (CD) of the small bowel is
      based on a typical history, tender right lower quadrant fullness or mass, and
      characteristic radiographic findings of the terminal ileum. Appendicitis may as
      well present with chronic or recurrent symptoms and this presentation may be
      confused with CD. We herein describe the case of a young teenage girl with a
      presumptive diagnosis of CD, who was ultimately diagnosed as having chronic
      nongranulomatous appendicitis. The literature on the subject is reviewed.

PMID- 16425407
TI  - Is there an association of microscopic colitis and irritable bowel syndrome--a
      subgroup analysis of placebo-controlled trials.

PMID- 16425408
TI  - Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis
      and virological characteristics of HBV genotype E.
AB  - AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin,
      and to clarify the virological characteristics of the dominant genotype. METHODS:
      Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the
      study. HBV genotypes were determined by enzyme immunoassay and restriction
      fragment length polymorphism. Complete genome sequences were determined by PCR
      and direct sequencing. RESULTS: HBV genotype E (HBV/E) was detected in 20/21
      (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to
      anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur
      frequently in late teens in HBV/E. The comparison of four complete HBV/E genomes
      from HBeAg-positive subjects in this study and five HBV/E sequences recruited
      from the database revealed that HBV/E was distributed throughout West Africa with
      very low genetic diversity (nucleotide homology 96.7-99.2%). Based on the
      sequences in the basic core promoter (BCP) to precore region of the nine HBV/E
      isolates compared to those of the other genotypes, a nucleotide substitution in
      the BCP, G1757A, was observed in HBV/E. CONCLUSION: HBV/E is predominant in the
      Republic of Benin,and SC is estimated to occur in late teens in HBV/E. The
      specific nucleotide substitution G1757A in BCP,which might influence the
      virological characteristics, is observed in HBV/E.

PMID- 16425409
TI  - Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis
      B.
AB  - AIM: To examine the serum from black African patients with acute hepatitis B to
      ascertain if integrants of viral DNA can be detected in fragments of cellular DNA
      leaking from damaged hepatocytes into the circulation. METHODS: DNA was extracted
      from the sera of five patients with uncomplicated acute hepatitis B and one with
      fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of
      HBV were used and the resulting amplicons were cloned and sequenced. RESULTS: HBV
      and chromosomal DNA were amplified from the sera of all the patients. In one
      patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7
      q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S
      and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right
      virus/host junction was situated at nucleotide 1,774 in the cohesive overlap
      region of the viral genome, at a preferred topoisomerase I cleavage motif. The
      chromosomal DNA was not rearranged. The patient made a full recovery and
      seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal
      DNA could be amplified from his serum at that time. CONCLUSION: Integration of
      viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and,
      with clonal propagation of the integrant, might play a role in
      hepatocarcinogenesis.

PMID- 16425410
TI  - Changes in lipid metabolism in chronic hepatitis C.
AB  - AIM: To investigate the relationship between certain biochemical parameters of
      lipid metabolism in the serum and steatosis in the liver. METHODS: The grade of
      steatosis (0-3) and histological activity index (HAI, 0-18) in liver biopsy
      specimens were correlated with serum alanine aminotransferase (ALT), total
      cholesterol and triglyceride levels in 142 patients with chronic hepatitis C (CH
      C), and 28 patients with non-alcoholic fatty liver disease (NAFLD) without
      hepatitis C virus (HCV) infection. The serum parameters were further correlated
      with 1,797 age and sex matched control patients without any liver diseases.
      RESULTS: Steatosis was detected in 90 out of 142 specimens (63%) with CH-C. The
      ALT levels correlated with the grade of steatosis, both in patients with CH-C and
      NAFLD (P<0.01). Inserting the score values of steatosis as part of the HAI,
      correlation with the ALT level (P<0.00001) was found. The triglyceride and
      cholesterol levels were significantly lower in patients with CH-C (with and
      without steatosis), compared to the NAFLD group and to the virus-free control
      groups. CONCLUSION: Our study confirms the importance of liver steatosis in CH-C
      which correlates with lower lipid levels in the sera. Inclusion of the score of
      steatosis into HAI, in case of CH-C might reflect the alterations in the liver
      tissue more precisely, while correlating with the ALT enzyme elevation.

PMID- 16425411
TI  - VP22 fusion protein-based dominant negative mutant can inhibit hepatitis B virus
      replication.
AB  - AIM: To investigate the inhibitory effect of VP22 fusion protein-based dominant
      negative (DN) mutant on Hepatitis Bvrus (HBV) replication. METHODS: Full-length
      or truncated fragment of VP22 was fused to C terminal of HBV core protein (HBc),
      and subcloned into pcDNA3.1 (-) vector, yielding eukaryotic expression plasmids
      of DN mutant. After transfection into HepG2.2.15 cells, the expression of DN
      mutant was identified by immunofluorescence staining. The inhibitory effect of DN
      mutant on HBV replication was indexed as the supernatant HBsAg concentration
      determined by RIA and HBV-DNA content by fluorescent quantification-PCR (FQ
      PCR).Meanwhile, metabolism of HepG2.2.15 cells was evaluated by MTT colorimetry.
      RESULTS: VP22-based DN mutants and its truncated fragment were expressed in
      HepG2.2.15 cells, and had no toxic effect on host cells. DN mutants could inhibit
      HBV replication and the transduction ability of mutant-bearing protein had a
      stronger inhibitory effect on HBV replication. DN mutants with full length of
      VP22 had the strongest inhibitory effect on HBV replication, reducing the HBsAg
      concentration by 81.94%, and the HBV-DNA content by 72.30%. MTT assay suggested
      that there were no significant differences in cell metabolic activity between the
      groups. CONCLUSION: VP22-based DN mutant can inhibit HBV replication effectively.

PMID- 16425412
TI  - Hepatitis C virus non-structural 5A protein can enhance full-length core protein
      induced nuclear factor-kappaB activation.
AB  - AIM: To study the effects of hepatitis C virus (HCV) core and non-structural 5A
      (NS5A) proteins on nuclear factor-kappaB (NF-kappaB) activity for understanding
      their biological function on chronic hepatitis caused by HCV infection. METHODS:
      Luciferase assay was used to measure the activity of NF-kappaB in three different
      cell lines cotransfected with a series of deletion mutants of core protein alone
      or together with NS5A protein using pNF-kappaB-Luc as a reporter plasmid. Western
      blot and indirect immunofluorescence assays were used to confirm the expression
      of proteins and to detect their subcellular localization, respectively.
      Furthermore, Western blot was also used to detect the expression levels of NF
      kappaB/p65, NF-kappaB/p50, and inhibitor kappaB-a (IkappaB-a). RESULTS: The wild
      type core protein (C191) and its mutant segments (C173 and C158) could activate
      NF-kappaB in Huh7 cells only and activation caused by (C191) could be enhanced by
      NS5A protein. Moreover, the full-length core protein and its different deletion
      mutants alone or together with NS5A protein did not enhance the expression level
      of NF-kappaB. The NF-kappaB activity was augmented due to the dissociation of NF
      kappaB-IkappaB complex and the degradation of IkappaB-a. CONCLUSION: NF-kappaB is
      the key transcription factor that can activate many genes that are involved in
      the cellular immune response and inflammation. Coexpression of the full-length
      core protein along with NS5A can enhance the NF-kappaB activation, and this
      activation may play a significant role in chronic liver diseases including
      hepatocellular carcinoma associated with HCV infection.

PMID- 16425413
TI  - Expression and immunoreactivity of HCV/HBV epitopes.
AB  - AIM: To develop the epitope-based vaccines to prevent Hepatitis C virus (HCV) /
      Hepatitis B virus (HBV) infections. METHODS: The HCV core epitopes C1
      STNPKPQRKTKRNTNRRPQD (residuals aa2-21) and C2 VKFPGGGQIVGGVYLLPRR (residuals
      aa22-40), envelope epitope E GHRMAWDMMMNWSP (residuals aa315-328) and HBsAg
      epitope S CTTPAQGNSMFPSCCCTKPTDGNC (residuals aa124-147) were displayed in five
      different sites of the flock house virus capsid protein as a vector, and
      expressed in E. coli cells (pET-3 system). Immunoreactivity of the epitopes with
      anti-HCV and anti-HBV antibodies in the serum from hepatitis C and hepatitis B
      patients were determined. RESULTS: The expressed chimeric protein carrying the
      HCV epitopes C1, C2, E (two times), L3C1-I2E-L1C2-L2E could react with anti-HCV
      antibodies. The expressed chimeric protein carrying the HBV epitopes S, I3S could
      react with anti-HBs antibodies. The expressed chimeric proteins carrying the HCV
      epitopes C1, C2, E plus HBV epitope S, L3C1-I2E-L1C2-L2E-I3S could react with
      anti-HCV and anti-HBs antibodies. CONCLUSION: These epitopes have highly specific
      and sensitive immunoreaction and are useful in the development of epitope-based
      vaccines.

PMID- 16425414
TI  - Cytochrome P450 2E1 high activity polymorphism in alcohol abuse and end-organ
      disease.
AB  - AIM: To investigate a possible role for a recently identified polymorphism in the
      gene of cytochrome P450 2E1, the presence of which is associated with high
      activity of the enzyme. METHODS: Two hundred and thirty-nine alcohol consumers,
      ICD 10.1/.2 (ALC), and 208 normal controls were studied. PCR amplification of the
      CYP2E1 gene region was performed to assess polymorphic variation. Fisher's exact
      test was used to assess the data. RESULTS: Twelve normal controls (5.8%)
      possessed the insertion. Five ALC (2.1%) had the insertion; of these 2 of 144
      with alcohol induced chronic pancreatitis, none of 28 with alcoholic liver
      disease and 3 of 67 without end-organ disease had the polymorphism. A
      significantly Lower frequency of subjects possessed the insertion than normal
      controls [P=0.049 (genotype analysis P=0.03)]. To further assess, if there was a
      relationship to alcohol problems per se or end-organ disease, we compared
      patients with alcohol induced end-organ disease vs alcoholic controls without end
      organ disease vs normal controls which again showed a significant difference
      [P=0.045 (genotype analysis, P=0.011)], further sub-group analysis did not
      identify which group(s) accounted for these differences. CONCLUSION: We have
      shown the frequencies of this high-activity polymorphism in alcohol related
      patient groups for the first time. The frequency is significantly less in
      alcoholics than normal controls, as with high activity polymorphisms of alcohol
      dehydrogenase. The biological significance, and whether the relevance is solely
      for alcoholism or is there a relationship to end-organ disease, would benefit
      from the assessment in the populations with a greater frequency of this
      polymorphism.

PMID- 16425415
TI  - Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via
      activation of prostaglandin, nitric oxide and sensory nerve pathways.
AB  - AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial
      and antioxidative properties but whether it influences the gastric defense
      mechanism and gastroprotection against ethanol- and stress-induced gastric
      lesions remains unknown. METHODS: We compared the effects of GSE on gastric
      mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h
      of water immersion and restraint stress (WRS) with or without (A) inhibition of
      cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX
      2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C)
      inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without
      intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS.
      One hour after ethanol and 3.5 h after the end of WRS, the number and area of
      gastric lesions were measured by planimetry, the gastric blood flow (GBF) was
      assessed by H2-gas clearance technique and plasma gastrin levels and the gastric
      mucosal generation of PGE2, superoxide dismutase (SOD) activity and
      malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were
      determined. RESULTS: Ethanol and WRS caused gastric lesions accompanied by the
      significant fall in the GBF and SOD activity and the rise in the mucosal MDA
      content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated
      gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions
      by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was
      similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE
      significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma
      gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with
      indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin
      denervation reversed the GSE-induced protection and the accompanying hyperemia.
      Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE
      restored the protection and accompanying hyperemic effects of GSE in rats with
      capsaicin denervation. CONCLUSION: GSE exerts a potent gastroprotective activity
      against ethanol and WRS-induced gastric lesions via an increase in endogenous PG
      generation, suppression of lipid peroxidation and hyperemia possibly mediated by
      NO and CGRP released from sensory nerves.

PMID- 16425416
TI  - Neutrophil engagement and septic challenge in acute experimental pancreatitis in
      rats.
AB  - AIM: To investigate the influence of neutrophil adhesion molecule blockade with
      monoclonal antibody (MoAb CD11b) and E. coli lipopolysaccharide (LPS)
      administration on experimental acute pancreatitis (AP). METHODS: AP was induced
      by four ip injections of cerulein (Cn) at 1-h intervals. MoAb CD 11b and LPS were
      administered at the beginning of the experiment. RESULTS: The neutrophil count
      and chemiluminescence were diminished at the beginning of AP. The oxidative
      stress parameters were found within the pancreatic gland. MoAb CD 11b used for AP
      resulted in a significant reduction of pancreatic infiltration and pancreatitis
      oxidative stress parameters. Serum interleukin-6 (IL-6) was not detected in AP
      animals, whereas high serum IL-6 concentration was noted only in animals
      receiving LPS. CONCLUSION: Neutrophils are involved in pancreatic damage in the
      early stage of AP. Neutrophil infiltration reduction protects the pancreatic
      gland from destruction during AP. LPS does not change the early course of Cn
      pancreatitis in rats.

PMID- 16425417
TI  - Bile salts inhibit growth and induce apoptosis of culture human normal esophageal
      mucosal epithelial cells.
AB  - AIM: To investigate the effect of six bile salts: glycocholate (GC),
      glycochenodeoxycholate (GCDC), glycodeoxycholate (GDC), taurocholate (TC),
      taurochenodeoxycholate (TCDC), taurodeoxycholate (TDC), and their mixture on
      cultured human normal esophageal mucosal epithelial cells. METHODS: Human normal
      esophageal mucosal epithelial cells were cultured with serum-free keratinocyte
      medium.3-[4,5-Dimethylthiaolyl]-2,5-diphenyl-tetrazolium bromide assay was
      applied to the detection of cell proliferation. Apoptotic morphology was observed
      by phase-contrast video microscopy and terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) assay. Sub-G1 DNA fragmentations and
      early apoptotic cells were assayed by flow cytometry (FCM) with propidium iodide
      (PI) staining and annexin V-FITC conjugated with PI staining. Apoptotic DNA
      ladders on agarose gel electrophoresis were observed. RESULTS: Except for GC,
      GCDC, GDC, TC, TCDC, TDC and their mixture could initiate growth inhibition of
      esophageal mucosal epithelial cells in a dose- and time-dependent manner. TUNEL
      and FCM assays demonstrated that the bile salts at 500 mumol/L and their mixture
      at 1 500 micromol/L induced apoptosis except for GC. The percentage of sub-G1
      detected by FCM with PI staining was 83.5% in cells treated with 500 micromol/L
      TC for 2 h, and 19.8%, 20.4%, 25.6%, 13.5%, and 75.8% in cells treated with 500
      micromol/L GCDC, TCDC, GDC, TDC, and 1 500 micromol/L mixture for 24 h,
      respectively, which were higher than that of the control (1.5%). The percentage
      was 1.4% in cells with 500 micromol/L GC for 24 h. DNA ladders on agarose gel
      electrophoresis were seen in cells treated with 500 micromol/L TC for 2 h and 1
      500 micromol/L mixture for 24 h. CONCLUSION: All GCDC, GDC, TC, TCDC, TDC and
      their mixture can inhibit growth and induce apoptosis of cultured human normal
      esophageal mucosal epithelial cells, but GC is well tolerated by the cells.

PMID- 16425418
TI  - Effect of acupuncture at different meridian acupoints on changes of related
      factors for rabbit gastric mucosal injury.
AB  - AIM: To explore the regularity of multi-meridians controlling a same viscus
      (MMCSV). METHODS: The rabbit gastric ulcer model was established by ethanol
      intragastric instillation. Fifty-six rabbits were randomly divided into normal
      group, model group (MG), model plus acupuncture at Foot Yangming Meridian group
      (YMG), model plus acupuncture at Foot Taiyin Meridian group (TYG), model plus
      acupuncture at Foot Shaoyang Meridian group (SYG), model plus acupuncture at Foot
      Jueyin Meridian group (JYG), model plus acupuncture at Foot Taiyang Meridian
      group (TYMG), with eight rabbits in each group. Gastric mucosal nitric oxide (NO)
      and nitric oxide synthase (NOS) were assayed by the nitric acid reductase method,
      and prostaglandin E2 (PGE2) and epidermal growth factor (EGF) were measured by
      radioimmunoassay. The comprehensive effects were analyzed by weighing method.
      RESULTS: Compared to MG, SYG, JYG and TYMG, the rabbits gastric mucosal injury
      index (GMII) reduced very significantly in YMG (P<0.01). Compared to MG, the GMII
      also reduced significantly in TYG (P<0.05). NO, NOS, PGE2 and EGF increased very
      significantly in YMG (P<0.01). The EGF in YMG also increased significantly than
      that in TYG compared to those in MG, SYG, JYG and TYMG (P<0.05). The PGE2 and EGF
      also increased very significantly in TYG than those in MG, JYG and TYMG (P<0.01).
      While compared to SYG, the NOS increased significantly in TYG (P<0.05). NOS was
      the highest in YMG (P<0.01), and was higher in TYG than in MG (P<0.01).
      CONCLUSION: MMCSV is common. The Foot Yangming Meridian is most closely related
      to the stomach, followed by Foot Taiyin Meridian, Foot Shaoyang Meridian and Foot
      Jueyin Meridian. Foot Taiyang Meridian has no correlation with the stomach.

PMID- 16425419
TI  - Acid fibroblast growth factor reduces rat intestinal mucosal damage caused by
      ischemia-reperfusion insult.
AB  - AIM: To detect the effects of acid fibroblast growth factor (aFGF) on apoptosis
      and proliferation of intestinal epithelial cells in differentiation or
      proliferation status to explore the protective mechanisms of aFGF. METHODS:
      Wistar rats were randomly divided into sham-operated control group (C, n=6),
      intestinal ischemia group (I, n=6), aFGF treatment group (A, n=48) and intestinal
      ischemia-reperfusion group (R, n=48). Apoptosis of intestinal mucosal cells was
      determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end labeling (TUNEL) technique. Proliferating cell nuclear antigen (PCNA) protein
      expression and distribution were detected with immunohistochemical method. Plasma
      levels of D-lactate were determined with modified Brandts method. RESULTS: In A
      group, administration of exogenous aFGF could improve intestinal histological
      structure and decrease plasma D-lactate levels at 2-12 h after the reperfusion
      compared with R group. The apoptotic rates and PCNA protein expressions were not
      increased until 2 h after reperfusion and were maximal at 12 h. After reperfusion
      for 2-12 h, the apoptotic rates were gradually augmented along the length of
      jejunal crypt-villus units. Administration of aFGF could significantly reduce the
      apoptotic response at 2-12 h after reperfusion (P<0.05). Apoptosis rates in
      villus and crypt epithelial cells in A group at 12 h after reperfusion were
      (62.5+/-5.5)% and (73.2+/-18.6)% of those in R group, respectively. Treatment of
      aFGF could apparently induce protein expression of PCNA in intestinal mucosal
      cells of A group compared with R group during 2-12 h after reperfusion (P<0.05).
      There were approximately 1.3- and 1.5-times increments of PCNA expression levels
      in villus and crypt cells in A group at 12 h after reperfusion compared with R
      group, respectively. CONCLUSION: Intestinal I/R insult could lead to histological
      structure change and apoptotic rate increment. The protective effects of aFGF
      against ischemia/reperfusion in rat intestinal mucosa might be partially due to
      its ability to inhibit ischemia/reperfusion-induced apoptosis and to promote cell
      proliferation of crypt cells and villus epithelial cells.

PMID- 16425420
TI  - Pathological mechanisms of alcohol-induced hepatic portal hypertension in early
      stage fibrosis rat model.
AB  - AIM: To study the role of hepatic sinusoidal capillarization and perisinusoidal
      fibrosis in rats with alcohol-induced portal hypertension and to discuss the
      pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS:
      Fifty SD rats were divided into control group (n=20) and model group (n=30).
      Alcoholic liver fibrosis rat model was induced by intragastric infusion of a
      mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in
      each group were killed at wk 16. The diameter and pressure of portal vein were
      measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN)
      were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and
      6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver
      tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic
      non-parenchymal cells were isolated, total protein was extracted and separated by
      SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting.
      RESULTS: The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, P<0.01) and pressure
      (11.014+/-0.395 vs 8.533+/-0.274 mmHg, P<0.01) of portal vein were significantly
      higher in model group than those in the control group. Plasma HA (129.97+/-16.10
      vs 73.09+/-2.38 ng/mL, P<0.01), ColIV (210.49+/-4.36 vs 89.65+/-4.42 ng/mL,
      P<0.01) and LN (105.00+/-7.29 vs 55.70+/-4.32 ng/mL, P<0.01) were upregulated in
      model group. Abundant collagen deposited around the central vein of lobules,
      hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased
      remarkably and perisinusoids were almost surrounded by ColIII.
      Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs
      0.032+/-0.004, P<0.01) and LN protein level (0.152+/-0.005 vs 0.029+/-0.005,
      P<0.01) were up-regulated remarkably in model group. MMP-2 protein expression
      (2.306+/-1.089 vs 0.612+/-0.081, P<0.01) and TIMP-1 protein expression (3.015+/
      1.364 vs 0.446+/-0.009, P<0.01) in freshly isolated hepatic non-parenchymal cells
      were up-regulated in model group and TIMP-1 protein expression was evidently
      higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, P<0.05).
      CONCLUSION: Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are
      responsible for alcohol-induced portal hypertension in rats.

PMID- 16425421
TI  - Effects of angiotensin II receptor antagonist, Losartan on the apoptosis,
      proliferation and migration of the human pancreatic stellate cells.
AB  - AIM: To investigate the effects of AT1 (Type 1 angiotensin II receptor)
      antagonist (Losartan) on the apoptosis, proliferation and migration of the human
      pancreatic stellate cells (hPSCs). METHODS: hPSCs were isolated from pancreatic
      sample of patients with pancreatic carcinoma using radioimmunoassay (RIA)
      technique to detect the concentration of AngII in culture media and cell
      homogenate. Immunocytochemistry (ICC) and in situ hybridization (ISH) methods
      were utilized to test AT1 expression in hPSCs. Effects of Losartan on hPSCs
      proliferation, apoptosis and migration were investigated using BrdU
      incorporation, TUNEL, flow cytometry (FCM), and phase-contrast microscope
      separately when cells treated with Losartan. Immunofluorescence and Western blot
      were applied to quantify the expression of type I collagen in hPSCs. RESULTS:
      There exists AT1 expression in hPSCs, while no AngII was detected in culture
      media and cell homogenate. Losartan induces cell apoptosis in a dose- and time
      dependent manner (apparently at 10(-5) mol/L), no pro-proliferative effect was
      observed in the same condition. Corresponding dosage of Losartan can also
      alleviate the motion capability and type I collagen content of hPSCs compared
      with AngII treatment and non-treatment control groups. CONCLUSION: These findings
      suggest that paracrine not autocrine functions of AngII may have effects on
      hPSCs, which was mediated by AT1 expressed on cells, while Losartan may exert
      anti-fibrotic effects by inhibiting hPSCs motion and partly by inducing
      apoptosis.

PMID- 16425422
TI  - Differential effects of glutamate receptor antagonists on dorsal horn neurons
      responding to colorectal distension in a neonatal colon irritation rat model.
AB  - AIM: To investigate and compare the effects of spinal D-(-)-2-amino-7
      phosphonoheptanoic acid (AP-7) and 6-cyano-7-nitroquinoxaline-2,3-dione disodium
      (CNQX), two glutamate receptor antagonists, on the responses of dorsal horn
      neurons to colorectal distension (CRD) in adult rats exposed to neonatal colon
      irritation (CI). METHODS: Hypersensitive SD rats were generated by CI during
      postnatal days 8, 10 and 12. Experiments on adult rats were performed using
      extracellular single-unit recording. The effects of spinal application of AP-7
      (0.001, 0.01, 0.1, 1 mmoL) were tested on the CRD-evoked neuronal responses in 16
      controls and 17 CI rats. The effects of CNQX (0.2, 2, 5, 10 micromoL) were also
      tested on the CRD-evoked responses of 17 controls and 18 CI neurons. RESULTS: (1)
      The average responses of lumbosacral neurons to all intensities of CRD in CI rats
      were significantly higher than those in control rats; (2) In control rats, AP-7
      (0.01 mmoL) had no significant effect on the neuronal response to all intensities
      of CRD (20, 40, 60, 80 mmHg); while AP-7 (0.1 mmoL) inhibited the neuronal
      response to 80-mmHg CRD. By contrast, in CI rats, AP-7 (0.01-1 mmoL) attenuated
      the CRD-evoked neuronal responses to all distention pressures in a dose-dependent
      manner; (3) In control rats, CNQX (2 micromoL) had no significantly effect on the
      neuronal response to all intensities of CRD; however, CNQX (5 micromoL)
      significantly attenuated the responses to CRD in the 40-80 mmHg range. By
      contrast, CNQX (2-10 micromoL) significantly decreased the neuronal responses in
      CI rats to non-noxious and noxious CRD in a dose-dependent manner. CONCLUSION:
      Our results suggest that spinal N-methyl-D-aspartate (NMDA) and non-NMDA
      receptors may contribute to the processing of central sensitivity in a neonatal
      CI rat model, but they may play different roles in it.

PMID- 16425423
TI  - Narrow portion of the terminal choledochus is a cause of upstream biliary
      dilatation in patients with anomalous union of the pancreatic and biliary ducts.
AB  - AIM: To clarify the pathogenesis of biliary dilatation associated with anomalous
      union of the pancreatic and biliary ducts (AUPBD). METHODS: Direct
      cholangiopancreatograms of 350 adult patients with or with suspicion of
      hepatobiliary or pancreatic disorders were reviewed. AUPBD was diagnosed
      cholangiopancreatographically, when the pancreaticobiliary ductal union was
      located above the narrow distal segment of the bile duct, which represents the
      action of the sphincter of Oddi. The narrow portion of the terminal choledochus
      was defined as symmetrical stricture of the common bile duct just above the
      pancreaticobiliary ductal union. RESULTS: AUPBD was found in 36 patients. Among
      cholangiopancreatographic features, the narrow portion of the terminal
      choledochus was the most pathognomonic for AUPBD (accuracy, 98%); it was present
      in 29 (81%) patients with AUPBD, but was not found in any patients without AUPBD.
      Among patients with AUPBD, biliary dilatation (>10 mm) was more frequent in those
      with the narrow portion of the terminal choledochus (23/29) than in those without
      (2/7; P=0.018) AUPBD. Among the patients with both AUPBD and the narrow portion
      of the terminal choledochus, there was a strong negative correlation between the
      minimum diameter of the narrow portion and the maximum diameter of the
      choledochus (r=-0.78, P<0.001), suggesting that the degree of biliary narrowing
      at the narrow portion correlates with that of upstream biliary dilatation.
      CONCLUSION: The narrow portion of the terminal choledochus, a pathognomonic
      radiologic feature of AUPBD, may be a cause of biliary dilatation in patients
      with AUPBD.

PMID- 16425424
TI  - Prevalence of gallstone disease in first-degree relatives of patients with
      cholelithiasis.
AB  - AIM: To evaluate the influence of familiality on the prevalence of gallstone
      disease (GD) in Italy. METHODS: Families of 79 subjects with gallstones (cases)
      and of 79 subjects without gallstones (controls) were investigated for the
      presence of gallstones by ultrasonography. Index cases and index controls were
      matched for age, sex, and operative unit. Sixty-three and sixty-two husbands and
      wives of index cases and index controls, respectively, were also studied.
      RESULTS: Overall, the prevalence of GD was significantly higher (c2=14.52,
      P<0.001) in the 202 first-degree relatives of subjects with gallstones than that
      in the 201 first-degree relatives of subjects without gallstones (28.6% vs 12.4%,
      relative risk (RR) 1.80, 95% confidence interval (CI) 1.29-2.63). In particular,
      prevalence of GD was significantly higher in mothers, fathers, and sisters of
      index cases than that in the respective family members of index controls. The
      highest RR was observed in mothers (RR=2.35, 95%CI 1.38-4.3). Prevalence of GD
      was not obviously different in brothers and also in husbands and wives of index
      cases and index controls. Family members of index cases did not differ from
      family members of control cases with respect to the most important risk factors
      for gallstones (age, diabetes, BMI, and number of pregnancies) with an exception
      of a higher prevalence of diabetes in fathers of index controls than in fathers
      of index cases. CONCLUSION: This study confirms that familiality plays a very
      important role in the pathogenesis of gallstones.

PMID- 16425425
TI  - Genistein inhibits invasive potential of human hepatocellular carcinoma by
      altering cell cycle, apoptosis, and angiogenesis.
AB  - AIM: To study the in vitro and in vivo inhibitory effects of genistein on
      invasive potential of Bel 7402 hepatocellular carcinoma (HCC) cells and to
      explore the underlying mechanism. METHODS: Bel 7402 HCC cells were exposed to
      genistein. The invasive activity of tumor cells was assayed in transwell cell
      culture chamber. p125FAK expression and cell cycle were evaluated by a functional
      assay. Cell apoptosis analysis was performed with TUNEL method. In addition,
      bilateral subrenal capsule xenograft transplantation of HCC was performed in 10
      nude mice. Genistein was injected and the invasion of HCC into the renal
      parenchyma was observed. Microvessels with immunohistochemical staining were
      detected. RESULTS: Genistein significantly inhibited the growth of Bel 7402
      cells, the inhibitory rate of tumor cells was 26-42%. The invasive potential of
      Bel 7402 cells in vitro was significantly inhibited, the inhibitory rate was 11
      28%. Genistein caused G2/M cell cycle arrest, S phase decreased significantly.
      The occurrence of apoptosis in genistein group increased significantly. The
      expression of p125FAK in 5 microg/mL genistein group (15.26+/-0.16%) and 10
      microg/mL genistein group (12.89+/-0.36%) was significantly lower than that in
      the control group (19.75+/-1.12%, P<0.05). Tumor growth in genistein-treated nude
      mice was significantly retarded in comparison to control mice, the inhibitory
      rate of tumor growth was about 20%. Genistein also significantly inhibited the
      invasion of Bel 7402 cells into the renal parenchyma of nude mice with xenograft
      transplant. The positive unit value of microvessels in genistein-treated group
      (10.422+/-0.807) was significantly lower than that in control group (22.330+/
      5.696, P<0.01). CONCLUSION: Genistein can effectively inhibit the invasive
      potential of Bel 7402 HCC cells by altering cell cycle, apoptosis and
      angiogenesis, inhibition of focal adhesion kinase may play a significant role in
      this process.

PMID- 16425426
TI  - Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal
      metaplasia: a 3-year follow-up study.
AB  - AIM: To investigate the effect of H pylori eradication on atrophic gastritis and
      intestinal metaplasia (IM). METHODS: Two hundred and fifty-nine patients with
      atrophic gastritis in the antrum were included in the study, 154 patients were
      selected for H pylori eradication therapy and the remaining 105 patients served
      as untreated group. Gastroscopy and biopsies were performed both at the beginning
      and at the end of a 3-year follow-up study. Gastritis was graded according to the
      updated Sydney system. RESULTS: One hundred and seventy-nine patients completed
      the follow-up, 92 of them received H pylori eradication therapy and the remaining
      87 H pylori-infected patients were in the untreated group. Chronic gastritis,
      active gastritis and the grade of atrophy significantly decreased in H pylori
      eradication group (P<0.01). However, the grade of IM increased in H pylori 
      infected group (P<0.05). CONCLUSION: H pylori eradication may improve gastric
      mucosal inflammation, atrophy and prevent the progression of IM.

PMID- 16425427
TI  - Significance and relationship between infiltrating inflammatory cell and tumor
      angiogenesis in hepatocellular carcinoma tissues.
AB  - AIM: To investigate the relationship between infiltrating inflammatory cell and
      tumor angiogenesis in hepatocellular carcinoma (HCC) tissues and their
      clinicopathological features. METHODS: The paraffin-embedded specimens from 70
      cases with HCC were stained using EliVision immunohistochemistry with mAbs
      against CD68, tryptase, and CD34. The counts of tumor-associated macrophage
      (TAM), mast cell (MC) and tumor microvessel (MV) were performed in the tissue
      sections. RESULTS: The mean counts of TAM, MC, and MV in HCC tissues were
      significantly higher than those in pericarcinomatous liver tissues (TAM: 69.31+/
      11.58 vs 40.23+/-10.36; MC:16.74+/-5.67 vs 7.59+/-4.18; MV: 70.11+/-12.45 vs
      38.52+/-11.16, P<0.01). The MV count in the patients with metastasis was markedly
      higher than that with non-metastasis (P<0.01). In addition, the MC count in the
      patients with poorly differentiated HCC was obviously higher than that with well
      differentiated HCC (P<0.01). The correlation analysis showed that the TAM count
      was significantly correlated with the count of MV (r=0.712, P<0.01), and the MC
      count was obviously correlated with the MV count (r=0.336, P<0.05). CONCLUSION:
      TAM and MC might be closely related to the enhancement of tumor angiogenesis. The
      MV count might be associated with tumor invasion and metastasis. Moreover, the MC
      count might be associated with tumor differentiation and prognosis of HCC.

PMID- 16425428
TI  - Clinical characteristics and distribution of hepatitis B virus genotypes in
      Guangxi Zhuang population.
AB  - AIM: To investigate the distribution of HBV genotypes and their YMDD mutations in
      Guangxi Zhuang population, China, and to study the relationship between HBV
      genotypes and clinical types of HB, ALT, HBV DNA, HBe system as well as the
      curative effect of Lamivudine (LAM) on hepatitis B. METHODS: A total of 156 cases
      were randomly chosen as study subjects from 317 patients with chronic hepatitis B
      (CHB). HBV genotypes were determined by PCR-microcosmic nucleic acid cross-ELISA.
      YMDD mutations were detected by microcosmic nucleic acid cross-nucleic acid
      quantitative determination. HBV DNA was detected by fluorescence ratio PCR
      analysis. LAM was given to 81 cases and its curative effect was observed by
      measuring ALT, HBV DNA load, HBeAg, and HBeAg/HBeAb conversion rate. RESULTS: HBV
      genotypes B, C, D, and non-classified genotypes were found in Guangxi Zhuang
      population. accounting for 25.6%, 47.4%, 58.3%, and 16.0%, respectively. Seventy
      four cases were CD-, CB-, BD-mixed genotypes (47.7%). Forty-six (29.5%) cases had
      YMDD mutations. Genotype B was mostly found in mild and moderate CHB patients.
      Genotypes C, D and mixed genotype mostly occurred in severe CHB cases. Genotypes
      D and CD HBV-infected patients had higher ALT and HBV DNA than patients with
      other types of HBV infection. There was no significant difference among the
      genotypes in YMDD mutations, clinical types, ALT and HBV DNA level. Non
      classified types geno had a significantly lower positive rate of HBeAg than other
      genotypes (c2=12.841, P<0.05). There was no significant difference in ALT
      recovery rate, HBV DNA load, HBeAg, and HBeAg/HBeAb conversion rate, 48 wk after
      LAM treatment between groups of genotypes D, CD, and non-classified type.
      CONCLUSION: Genotypes B, C, and D, non-classified and mixed genotype of HBV are
      identified in the Guangxi Zhuang population. Variations in genotypes are
      associated with clinical severity and serum ALT levels, but not with YMDD
      mutation or HBV DNA load. Therapeutic effects of LAM on clinical parameters are
      not influenced by differences in genotypes. Further studies are needed to gain an
      in-depth understanding of the relationship between HBV genotypes and serum HBeAb
      and HBeAg.

PMID- 16425430
TI  - Quantitative evaluation of diffusion-weighted magnetic resonance imaging of focal
      hepatic lesions.
AB  - AIM: To explore the quantitative analysis of diffusion-weighted magnetic
      resonance imaging (DWMRI) in differential diagnosis of focal hepatic lesions.
      METHODS: DWMRI was performed in 149 hepatic lesions, including hepatocellular
      carcinoma (34 cases), hepatic metastases (37 cases), cavernous hemangioma (42
      cases), hepatic cyst (36 cases). Apparent diffusion coefficient (ADC) values were
      evaluated using four different b values in different sequences. The ratio of ADC
      values of lesion/liver in hepatocellular carcinoma and hepatic metastases was
      also calculated. RESULTS: The mean ADC values of hepatic lesions were as follows:
      hepatocellular carcinoma (0.95+/-0.11)x10(-3) mm2/s, hepatic metastasis (1.13+/
      0.21)x10(-3)mm2/s, cavernous hemangioma (1.86+/-0.36)x10(-3) mm2/s, hepatic cyst
      (3.14+/-0.31)x10(-3) mm2/s. The ratio of ADC values in lesion/liver in
      hepatocellular carcinoma was 0.91+/-0.11, being significantly different from that
      in hepatic metastasis (1.21+/-0.18, P<0.05). CONCLUSION: ADC values and
      quantitative analysis of focal hepatic lesions are of significant values in
      differential diagnosis of focal hepatic lesions.

PMID- 16425429
TI  - Correlation between CK18 gene and gastric carcinoma micrometastasis.
AB  - AIM: To explore the biological behavior of gastric carcinoma micrometastasis (MM)
      with a marker of cytokeratin 18 (CK18) and to evaluate the clinical stage of
      gastric carcinoma and its prognosis. METHODS: Reverse transcription-polymerase
      chain reaction (RT-PCR) was used to examine the expression of CK18 mRNA in 298
      lymph nodes from 35 patients with gastric carcinoma and 20 lymph nodes from 10
      patients with chronic peptic ulcer and gastric perforation diagnosed by
      pathological examination and surgery. CK18 mRNA expression of peripheral blood
      from 54 patients with gastric carcinoma and 10 healthy people were also examined.
      RESULTS: Expression of CK18 mRNA was not found in 10 patients with benign
      pathological changes. CK18 mRNA expression in gastric carcinoma tissues was
      strongly positive. In gastric carcinoma patients, pathological examination
      revealed that 99 of 298 (33.2%) lymph nodes were positive, while RT-PCR showed
      that 133 of 298 (44.6%) lymph nodes had expression of CK18 mRNA. The difference
      was significant (P<0.05). Among the 199 negative lymph nodes identified by
      pathological examinations, 34 (17.1%) displayed positive expression of CK18 mRNA
      by RT-PCR. The positive expression of CK18 mRNA was associated with lymph node
      micrometastasis (LMM) of gastric carcinoma. CK18 mRNA was negatively expressed in
      all 10 healthy cases and positively expressed in 38.9% of 54 blood specimens from
      gastric carcinoma patients. The positive rate was not correlated with tumor
      invasion of gastric carcinoma, but was significantly associated with TNM stage,
      lymph node metastasis (P=0.0290, P<0.05) and tumor differentiation (P=0.2956,
      P<0.05). CONCLUSION: RT-PCR with CK18 mRNA as a molecular marker is highly
      sensitive and specific in detecting LMM of gastric carcinoma. It can benefit the
      diagnosis of MM and guide studies on biological behavior, clinical phase, and
      therapy as well as relapse monitoring.

PMID- 16425431
TI  - Dual effects of 8-Br-cAMP on differentiation and apoptosis of human esophageal
      cancer cell line Eca-109.
AB  - AIM: To investigate the effects of 8-Br-cAMP on differentiation and apoptosis of
      human esophageal cancer cell line Eca-109, and the related gene expression.
      METHODS: The cultured Eca-109 cells were divided into four groups: E1 group (co
      cultured with 8-Br-cAMP for 24 h); E2 group (co-cultured with 8-Br-cAMP for 48
      h); C1 group (treated without 8-Br-cAMP for 24 h); and C2 group (treated without
      8-Br-cAMP for 48 h). The same concentration of cell suspension of each group was
      dropped separately onto the slides and nitrocellulose membranes (NCM). The biotin
      labeled cDNA probes for c-myc, wild-type (wt) p53, bcl-2 and iNOS were prepared
      for in situ hybridization. The expressions of epidermal growth factor receptor
      (EGFR), p38 kinase, FAS, FasL and caspase-3 were detected using
      immunocytochemistry, and the NOS activity and the ratio of differentiated
      cells/proliferating cells were examined by cytochemistry. Immunocytochemistry,
      cytochemistry, and in situ hybridization were separately carried out on both
      slides and NCM specimens for each group. In addition, TUNEL was used to detect
      the cell apoptosis rate in each group. RESULTS: The apoptotic rate of E2 group
      was significantly higher compared to E1 group, while there was no difference in
      the ratio of differentiated cells/proliferating cells between E1 and E2 groups.
      The signals of wt p53 and iNOS were markedly stronger, while the signals of c-myc
      and EGFR were obviously weaker in E1 group than those in C1 group (P<0.05).
      Moreover, the signals of wt p53, iNOS, p38 kinase, caspase-3 and NOS activity
      were significantly stronger, whereas, the signals of bcl-2, c-myc and Fas/FasL
      were markedly weaker in E2 group than those in C2 group (P<0.05). CONCLUSION: The
      differentiation and apoptosis of human esophageal cancer cell Eca-109 can be
      induced after 24- and 48-h treatment with 8-Br-cAMP, respectively. Upregulation
      of wt p53, iNOS and downregulation of c-myc may be associated with
      differentiation and apoptosis of Eca-109 cells. Furthermore, upregulation of
      FasL, p38 kinase and caspase-3 as well as downregulation of bcl-2, and Fas may be
      involved in the apoptosis of Eca-109 cells.

PMID- 16425432
TI  - Discovery and analysis of pancreatic adenocarcinoma genes using cDNA microarrays.
AB  - AIM: To study the pathogenetic processes and the role of gene expression by
      microarray analyses in expediting our understanding of the molecular
      pathophysiology of pancreatic adenocarcinoma, and to identify the novel cancer
      associated genes. METHODS: Nine histologically defined pancreatic head
      adenocarcinoma specimens associated with clinical data were studied. Total RNA
      and mRNA were isolated and labeled by reverse transcription reaction with Cy5 and
      Cy3 for cDNA probe. The cDNA microarrays that represent a set of 4 096 human
      genes were hybridized with labeled cDNA probe and screened for molecular
      profiling analyses. RESULTS: Using this methodology, 184 genes were screened out
      for differences in gene expression level after nine couples of hybridizations. Of
      the 184 genes, 87 were upregulated and 97 downregulated, including 11 novel human
      genes. In pancreatic adenocarcinoma tissue, several invasion and metastasis
      related genes showed their high expression levels, suggesting that poor prognosis
      of pancreatic adenocarcinoma might have a solid molecular biological basis.
      CONCLUSION: The application of cDNA microarray technique for analysis of gene
      expression patterns is a powerful strategy to identify novel cancer-associated
      genes, and to rapidly explore their role in clinical pancreatic adenocarcinoma.
      Microarray profiles provide us new insights into the carcinogenesis and invasive
      process of pancreatic adenocarcinoma. Our results suggest that a highly organized
      and structured process of tumor invasion exists in the pancreas.

PMID- 16425433
TI  - No relationship between IL-1B gene polymorphism and gastric acid secretion in
      younger healthy volunteers.
AB  - AIM: To investigate the influence of IL-1B-511 gene polymorphism on IL-1B mRNA
      expression and gastric acid output in individual with or without Helicobacter
      pylori (H pylori) infection. METHODS: IL-1B mRNA expression and gastric acid
      secretion in 117 health volunteers were assayed using semi-quantitative RT-PCR
      and gastric juice assay, respectively. Pepsinogen (PG) I and II of 255 subjects
      (including 117 health volunteers) were also examined. RESULTS: T/T genotype
      individuals with H pylori infection had a more decreased PG I/II ratio. In
      gastric antrum mucosa, the individuals with H pylori infection had higher IL-1B
      expression than those without H pylori infection, but there was no obvious
      difference among each genotype. In gastric corpus, the individuals with H pylori
      infection had a significantly higher IL-1B expression than those without H pylori
      infection. IL-1B-511T/T genotype was markedly higher as compared with the other
      two genotypes. Both maximal acid output and basic acid output were similar among
      each genotype in IL-1B-511 gene locus, regardless of H pylori infection.
      CONCLUSION: IL-1B-511 T allele does not decrease gastric acid output, although it
      has a stimulated influence on IL-1B expression. Consequently, the pathway,
      through which IL-1B plays a central role in gastric cancer development, might not
      depend on low acid, but on the other regulation mechanisms.

PMID- 16425434
TI  - Peroral cholangioscopy for non-invasive papillary cholangiocarcinoma with
      extensive superficial ductal spread.
AB  - Papillary carcinoma arising from the extrahepatic bile duct often shows
      superficial ductal spread. We report herein the case of a patient with extensive
      superficial spread of non-invasive papillary cholangiocarcinoma, which was
      depicted with peroral cholangioscopy. A 65-year-old woman presented with the
      sudden-onset of severe epigastric pain. Ultrasonography revealed acute acalculous
      cholecystitis. Endoscopic retrograde cholangiography found small protruding
      lesions around the confluence of the cystic duct, suggestive of a
      cholangiocarcinoma. As the contour of the middle and upper bile ducts it was
      slightly irregular on the cholangiogram, the presence of superficial ductal
      spread was suspected. Peroral cholangioscopy revealed small papillary lesions
      around the confluence of the cystic duct and fine granular mucosal lesions in the
      middle and upper bile ducts and the right hepatic duct, suggesting a
      superficially spreading tumor. A right hepatectomy with bile duct resection was
      performed and no residual tumor was found. Histological examination revealed a
      non-invasive papillary carcinoma arising from the cystic duct with extensive
      superficial spread. Our experience of this case and a review of the literature
      suggest that a fine granular or fine papillary appearance of the ductal mucosae
      on cholangioscopy indicates superficial spread of papillary cholangiocarcinoma,
      for which peroral cholangioscopy is an efficient diagnostic option.

PMID- 16425435
TI  - Left paraduodenal hernia presenting as recurrent small bowel obstruction.
AB  - Internal herniation of the small bowel is a relatively rare cause of intestinal
      obstruction. Left paraduodenal hernia resulting from abnormal rotation of the
      midgut during embryonic development is the most common form of congenital
      internal hernia. We report our experience in the diagnosis and management of a
      young male with left paraduodenal hernia presenting as recurrent intestinal
      obstruction. Correct preoperative diagnosis of left paraduodenal hernia had been
      difficult due to non-specific clinical presentations, but the advent of modern
      imaging technology makes early and correct diagnosis possible. Due to the risk of
      obstruction and strangulation, surgical treatment is indicated; however, timely
      intervention increases the likelihood of a favorable outcome.

PMID- 16425436
TI  - Splenic angiosarcoma metastasis to small bowel presented with gastrointestinal
      bleeding.
AB  - Primary splenic angiosarcoma is a very rare, aggressive neoplasm with a high
      metastatic rate and dismal prognosis. This neoplasm usually presents with
      abdominal pain, splenomegaly, anemia, and thrombocytopenia. Splenic angiosarcoma
      with bleeding gastrointestinal metastases is extremely rare. The literature
      contains only two case reports. This study reported a 44-year-old male patient
      with splenic angiosarcoma with sustained repeated gastrointestinal bleeding due
      to small bowel metastases. Salvage surgery was performed by splenectomy and
      resection of the metastatic small bowel tumors. The post-operative course was
      uneventful; the patient survived with the disease and had no GI bleeding, 7 mo
      after surgery.

PMID- 16425437
TI  - Esophageal rupture due to Sengstaken-Blakemore tube misplacement.
AB  - The author presents three cases of esophageal rupture during the treatment of
      massive esophageal variceal bleeding with Sengstaken-Blakemore (SB) tube. In each
      case, simple auscultation was used to guide SB tube insertion, with chest
      radiograph obtained only after complete inflation of the gastric balloon. Two
      patients died of hemorrhagic shock and one died of mediastinitis. The author
      suggests that confirmation of SB tube placement by auscultation alone may not be
      adequate. Routine chest radiographs should be obtained before and after full
      inflation of the gastric balloon to confirm tube position and to detect tube
      dislocation.

PMID- 16425438
TI  - Advances in organic synthesis using polymer-supported reagents and scavengers
      under microwave irradiation.
AB  - Microwave-assisted and polymer-supported organic syntheses have emerged
      independently as versatile tools for rapid generation of organic molecules.
      Chemists are increasingly looking for a combination of both techniques for
      efficient organic synthesis. This review covers the recent literature on organic
      synthesis using microwave heating in conjunction with polymer-supported reagents
      and scavengers.

PMID- 16425440
TI  - Pioneers in cardiology.

PMID- 16425441
TI  - Propylthiouracil-induced lupus-like syndrome: successful management with oral
      corticosteroids.

PMID- 16425442
TI  - Reference values for thyrotropin.

PMID- 16425443
TI  - Disseminated medullary thyroid cancer after early thyroid surgery in multiple
      endocrine neoplasia type 2A.

PMID- 16425444
TI  - Pediatric facial fractures: recent advances in prevention, diagnosis and
      management.
AB  - During the last 25 years, there have been considerable advances in the
      prevention, diagnosis and management of craniomaxillofacial injuries in children.
      When compared to adults, the pattern of fractures and frequency of associated
      injuries are similar but the overall incidence is much lower. Diagnosis is more
      difficult than in adults and fractures are easily overlooked. Clinical diagnosis
      is best confirmed by computed tomographic (CT) scans. Treatment is usually
      performed without delay and can be limited to observation or closed reduction in
      non-displaced or minimally displaced fractures. Operative management should
      involve minimal manipulation and may be modified by the stage of skeletal and
      dental development. Open reduction and rigid internal fixation is indicated for
      severely displaced fractures. Primary bone grafting is preferred over secondary
      reconstruction and alloplastic materials should be avoided when possible.
      Children require long-term follow-up to monitor potential growth abnormalities.
      This article is a review of the epidemiology, diagnosis and management of facial
      fractures in children.

PMID- 16425445
TI  - Expression of acetylcholinesterase (AChE) and aryl acylamidase (AAA) during early
      zebrafish embryogenesis.
AB  - In zebrafish, the onset of acetylcholinesterase (AChE) expression was detected by
      RT-PCR at 4 hpf (hours post-fertilization). The aryl acylamidase (AAA) associated
      with AChE, a serotonin sensitive activity with unknown physiological function,
      was significantly higher than the esterase activity on zebrafish embryos
      homogenates at 4-12 h development (test-t = 3.523; d.f. = 4). Remarkably, the
      ratio of AAA/AChE activity decreased 210-fold from 4 to 144 h development,
      indicating a distinct embryonic role of AAA during early embryogenesis. The AAA
      activity was sensitive to eserine and serotonin, ensuring its association with
      AChE. This is the first report of AAA activity on fish, establishing zebrafish as
      a model to study AAA on development.

PMID- 16425446
TI  - Effects of time-variant extremely low-frequency (ELF) electromagnetic fields
      (EMF) on cholinesterase activity in Dictyostelium discoideum (Protista).
AB  - Recently, we detected propionylcholinesterase (PrChE) activity in single-cell
      amoebae of Dictyostelium discoideum using cytochemical, electrophoretic, and
      spectrophotometric methods. The involvement of this enzyme activity in cell-cell
      and cell-environment interactions was suggested. In this work, we found that
      exposure of single-cell amoebae to an extremely low-frequency electromagnetic
      fields (ELF-EMF) of 300 microT, 50 Hz, from 1 h up to 48 h at 21 +/- 1 degrees C
      affected PrChE activity.

PMID- 16425447
TI  - Light promotes the synthesis of lignin through the production of H2O2 mediated by
      diamine oxidases in soybean hypocotyls.
AB  - In order to analyze the relationship between polyamine oxidative degradation
      induced by light and the Lignin synthesis in cell walls, the activities of
      diamine oxidases and peroxidase, the contents of H2O2 and lignin, and the growth
      of hypocotyls in soybean [Glycine max (Linn.) Merr.] grown under tight or in
      darkness were investigated. In comparison with the dark treatment, light
      irradiation significantly inhibited the growth of soybean hypocotyls and promoted
      the activities of diamine oxidases and peroxidase as well as the accumulation of
      H2O2 and lignin. Treatments with the different concentrations of diamine oxidase
      inhibitors (2-hydroxyethylhydrazine and aminoguanidine) under the light condition
      inhibited diamine oxidase activity, and decreased the contents of H2O2 and
      lignin. The results provide evidence for the hypothesis that light irradiation
      could promote the accumulation of H2O2 and lignin in cell walls by activating
      polyamine oxidative degradation mediated by diamine oxidases.

PMID- 16425448
TI  - Effects of 6-methoxy-2-benzoxazolinone on the germination and alpha-amylase
      activity in lettuce seeds.
AB  - Germination of lettuce seeds was inhibited by 6-methoxy-2-benzoxazolinone (MBOA)
      at concentrations greater than 0.03 mmol/L. MBOA also inhibited the induction of
      alpha-amylase activity in the lettuce seeds at concentrations greater than 0.03
      mmol/L. These two concentration-response curves for the germination and alpha
      amylase indicate that the percentage of the germination was positively correlated
      with the activity of alpha-amylase in the seeds. Lettuce seeds germinated around
      18h after incubation and inhibition of alpha-amylase by MBOA occurred within 6h
      after seed incubation. These results show that MBOA may inhibit the germination
      of lettuce seeds by inhibiting the induction of alpha-amylase activity.

PMID- 16425449
TI  - Biochemical responses in leaves of two apple tree cultivars subjected to
      progressing drought.
AB  - The influence of water deprivation on potted apple trees (Malus domestica Borkh.)
      was investigated. Biochemical responses including ascorbic acid, glutathione
      (GSH), tocopherols, chlorophylls, carotenoids, free amino acids, and soluble
      carbohydrates were measured in leaves of diploid 'Elstar' and triploid 'Jonagold
      Wilmuta' subjected to progressive drought. Leaf water potential was chosen to be
      the primary indicator of water stress in tested plants. Time courses of measured
      biochemical parameters showed that mild drought did not significantly affect the
      chosen stress indicators. Moderate drought increased the concentrations of
      ascorbic acid, total GSH, beta-carotene, zeaxanthin and alpha-tocopherol,
      indicating the adaptation to oxidative stress in apple trees. Moderate drought
      also increased concentration of soluble carbohydrates, mostly due to increased
      sorbitol concentration. Severe drought negatively affected vitality of apple
      trees, and caused a decrease in sorbitol concentration. Severe drought also
      caused decreases in ascorbic acid, total GSH, beta-carotene, alpha-tocopherol and
      chlorophyll concentrations, which, together with the increase in oxidised GSH
      concentration, indicated severe damage due to oxidative stress. Severe drought
      increased free amino acid concentration, which was probably the result of
      increased proteolysis. Zeaxanthin concentration remained high even in leaves of
      apple trees subjected to severe drought stress. The results were similar for both
      tested apple cultivars.

PMID- 16425450
TI  - Nitric oxide reduces Cu toxicity and Cu-induced NH4+ accumulation in rice leaves.
AB  - Nitric oxide (NO) is a highly reactive, membrane-permeable free radical, which
      has recently emerged as an important antioxidant. Here we investigated the
      protective effect of NO against the toxicity and NH4+ accumulation in rice leaves
      caused by excess CuSO4 (10mmol L(-1)). It was found that free radical scavengers
      (sodium benzoate, thiourea, and reduced glutathione) reduced the toxicity and
      NH4+ accumulation in rice leaves caused by excess CuSO4. NO donor sodium
      nitroprusside (SNP) was also effective in reducing CuSO4-induced toxicity and
      NH4+ accumulation in rice leaves. The protective effect of SNP on the toxicity
      and NH4+ accumulation can be reversed by 2-(4-carboxy-2-phenyl)-4,4,5,5
      tetramethyl- imidazoline-1-oxyl-3-oxide, a NO scavenger, suggesting that the
      protective effect of SNP is attributable to NO released. Results obtained in the
      present study suggest that reduction of CuSO4-induced toxicity and NH4+
      accumulation by SNP is most likely mediated through its ability to scavenge
      active oxygen species.

PMID- 16425451
TI  - Differential effects of abscisic acid on desiccation tolerance and carbohydrates
      in three species of liverworts.
AB  - Tissues of three species of in vitro grown liverworts, Riccia fluitans,
      Pallavicinia lyellii, and Marchantia polymorpha, were subjected to rapid drying
      with and without preculture for 1 week on medium containing 10 microM ABA. ABA
      preculture initiated total desiccation tolerance in R. fluitans, whereas control
      tissues were killed after 30 min of drying. Survival was also improved in P.
      lyellii, whereas ABA did not affect survival of M. polymorpha after rapid drying.
      ABA treatment did, however, reduce the rate of water loss in M. polymorpha. Total
      soluble carbohydrates were increased in ABA-treated R. fluitans and P. lyellii,
      but not in M. polymorpha, although there was no correlation between survival and
      changes in the percentage of these carbohydrates as reducing sugars. These
      differences in response to ABA and desiccation likely reflect different
      adaptations of these three species to conditions in situ.

PMID- 16425452
TI  - The level of jasmonic acid in Arabidopsis thaliana and Phaseolus coccineus plants
      under heavy metal stress.
AB  - The effect of heavy metal stress as a potent abiotic elicitor for triggering an
      accumulation of jasmonic acid (JA) was investigated. Copper and cadmium in in
      vivo conditions induced accumulation of jasmonates in mature leaves of
      Arabidopsis thaliana and in young and oldest Phaseolus coccineus plants. The
      dynamics of jasmonate accumulation showed a biphasic character in both plants. In
      the first phase, after 7 (A. thaliana) or 14h (P. coccineus) of exposure to Cu or
      Cd, a rapid increase of JA level occurred, followed by a rapid decrease observed
      during 7 successive hours. In the next phase, a repeated but slow increase of JA
      content occurred. The heavy metal stress induced in particular a more stable
      (3R,7R) form of jasmonates. These results indicate that JA is connected with the
      mechanism of toxic action of both heavy metals in plants, differentially reacting
      to exogenous JA and possessing variable dynamics depending on the plants studied
      as well as their growth stage.

PMID- 16425453
TI  - Nucleotide specificity of the RNA editing reaction in pea chloroplasts.
AB  - A sensitive in vitro editing assay for the pea chloroplast petB editing site has
      been developed and utilized to study the mechanism of C-to-U editing in
      chloroplast extracts. The in vitro editing assay was characterized by several
      criteria including: linearity with extract amount; linearity over time;
      dependence on assay components; and specificity of editing site conversion. The
      increase in the extent C-to-U conversion of the petB editing site was nearly
      linear with the amount chloroplast protein extract added, although the reaction
      appeared to decline in rate after approximately 30 min. The assay was tested for
      the importance of various assay components, and the omission of protease
      inhibitor and ATP was shown to dramatically reduce the extent of the editing
      reaction. Sequence analysis of cDNA clones obtained after an in vitro editing
      reaction demonstrated that 12 of 17 (71%) clones were edited, and that no other
      nucleotide changes in these cDNAs were detected. Thus, the fidelity and
      specificity of the in vitro editing system appears to be excellent, and this
      system should be suitable to study both mechanism of the editing reaction and
      editing site selection. The in vitro editing reaction was strongly stimulated by
      the addition of ATP, and all four NTPs and dNTPs stimulated the editing reaction
      except for rGTP, which had no effect. Thus, the nucleotide specificity of the
      editing reaction is broad, and is similar in this respect to the mitochondrial
      editing system. Most enzyme or processes specifically utilize ATP or GTP for
      phosphorylation and the ability to substitute other NTPs and dNTPs is unusual.
      RNA helicases have a similar broad nucleotide specificity and this may reflect
      the involvement of an RNA helicase in plant organelle editing.

PMID- 16425454
TI  - Analysis and use of the tobacco eIF4A-10 promoter elements for transgene
      expression.
AB  - The eIF4A gene family codes for proteins which unwind secondary structures of
      mRNA during translational initiation. The tobacco eIF4A-10 promoter is one of a
      few of constitutive promoters found in plants. Research was conducted to identify
      the proximal promoter elements and to evaluate the potential application of the
      promoter for regulating transgene expression in a range of crop plants. A large
      intron (892 bp) in the leader sequence was found to be dispensable for
      constitutive promoter activity and did not contribute to the overall performance
      of the promoter. Deletion analysis showed that the upstream region between -151
      bp and -73bp relative to the transcriptional start site was essential for the
      high level of expression and the constitutive activity. The data indicated that
      the elements in this region may coordinate and compensate each other for the high
      levels of promoter expression. The downstream leader sequence also contained a
      strong quantitative enhancer element that was essential for the full activity of
      the eIF4A-10 promoter. The eIF-4A10 promoter was found to be active in a wide
      range of plant species and tissues indicating that it will be useful for the
      constitutive expression of transgenes in plants.

PMID- 16425455
TI  - Green, herbicide-resistant plants by particle inflow gun-mediated gene transfer
      to diploid bahiagrass (Paspalum notatum).
AB  - We have established an efficient particle-bombardment transformation protocol for
      the diploid non-apomictic genotype of the warm season forage crop Paspalum
      notatum (bahiagrass). A vector containing a herbicide resistance gene (bar)
      together with the GUS reporter gene was used in transformation experiments. The
      bar gene confers resistance to the herbicide bialaphos. An improved culture
      system, highly regenerative callus, dense in compact polyembryogenic clusters,
      was produced on medium with a high CuSO4 content at elevated temperature. Target
      tissue (360 calli) produced under these conditions yielded 52 rooted plants on
      herbicide-containing medium, and 22 of these plants were PCR-positive. DNA gel
      blot analysis revealed a copy number of 1-5 for the GUS gene in different
      independent transformants. There was no correlation between copy number and GUS
      activity. While conventional cultures yielded exclusively albino plants on
      herbicide-containing medium, improved culture conditions for the target tissue
      resulted in the recovery of 100% green transgenic plants. All green herbicide
      resistant regenerants were morphological normal and fertile.

PMID- 16425456
TI  - Poly-beta-hydroxybutyrate accumulation in Nostoc muscorum and Spirulina platensis
      under phosphate limitation.
AB  - Nostoc muscorum and Spirulina platensis were grown under phosphate deficiency in
      order to investigate the role of internal phosphate pool and activity of alkaline
      phosphatase on poly-beta-hydroxybutyrate (PHB) accumulation. PHB accumulation in
      N. muscorum increased to 22.7% of dry weight (dw) after 4 day of phosphate
      deficiency, while the internal phosphate pool reduced to the level of 0.02 microM
      mg dw(-1) at a maximum APase activity of 2.57nM PNP mg dw(-1) h(-1). In contrary,
      S. platensis depicted maxima of 1.39nM PNP mg dw(-1) h(-1) on day 30 of
      incubation, which was about 2 fold lower than the observed value of N. muscorum.
      PHB content in S. platensis remained low even after prolonged phosphate
      starvation, and a rise only up to 3.5% of dw was recorded on day 60 of phosphate
      deficiency. Supplementation of NADPH exogenously to S. platensis cultures grown
      under phosphate deficiency favoured PHB accumulation in 10, 20 and 30 days old
      cultures, but not in the cultures grown under phosphate deficiency for 60 days.
      The possible role of phosphate limitation on PHB accumulation is discussed.

PMID- 16425457
TI  - Patient safety alert. Health care workers may imperil patients by snubbing
      influenza vaccinations.

PMID- 16425458
TI  - Surface plasmon resonance-based highly sensitive optical touch sensor with a
      hybrid noise rejection scheme.
AB  - A surface plasmon resonance (SPR)-based optical touch sensor structure is
      proposed that provides high switch sensitivity and requires a weak activating
      force. Our proposed SPR-based optical touch sensor is arranged in a compact
      Kretschmann-Raether configuration in which the prism acting as our sensor head is
      coated with a metal nanofilm. Our optical-based noise rejection scheme relies on
      wavelength filtering, spatial filtering, and high reflectivity of the metal
      nanofilm, whereas our electrical-based noise reduction is obtained by means of an
      electrical signal filtering process. In our experimental proof of concept, a
      visible laser diode at a 655 nm centered wavelength and a prism made from BK7
      with a 50 nm thick gold layer on the touching surface are used, showing a 7.85 dB
      optical contrast ratio for the first touch. An estimated weak mechanical force of
      <0.1 N is also observed that sufficiently activates the desired electrical load.
      It is tested for 51 operations without sensor malfunction under typical and very
      high illumination of 342 and 3000 lx, respectively. In this case, a measured
      average optical contrast of 0.80 dB is obtained with a +/-0.47 dB fluctuation,
      implying that the refractive index change in a small 3.2% of the overall active
      area is enough for our SPR-based optical touch sensor to function properly.
      Increasing optical contrast in our SPR-based optical touch sensor can be
      accomplished by using a higher polarization-extinction ratio and a narrower
      bandwidth optical beam. A controlled environment and gold-coated surface using
      the thin-film sputtering technique can help improve the reliability and the
      durability of our SPR-based optical touch sensor. Other key features include ease
      of implementation, prevention of a light beam becoming incident on the user, and
      the ability to accept both strong and weak activating forces.

PMID- 16425459
TI  - [Assessment indicators of soil quality in hilly Loess plateau].
AB  - By the methods of sensitivity analysis, main component analsis and discriminant
      analysis, this paper screened the sensitive indicators from 32 soil attributes to
      assess the productivity and erosion-resistance ability of the soils in hilly
      Loess Plateau. The results showed that soil available phosphorus content, anti
      scouring ability, infiltration coefficient, labile organic carbon content,
      organic matter content and urease activity were the most sensitive indicators for
      soil quality assessment and the main targets for soil quality management and
      improvement, while soil biological indicators were with high and medium
      sensitivity. Five soil quality factors were summed up from 29 soil chemical,
      physical and biological attributes, i. e., organic matter, texture, phosphorus,
      porosity and microstructure. Except the factor porosity, the other four factors
      were significantly different between different land use types. Eight indicators
      including soil organic matter content, infiltration coefficient, anti-scouring
      ability, CEC, invertase activity, mean weight diameter (MWD) of aggregates,
      available phosphorus, and MWD of microaggregate were identified as the assessment
      indicators of the soil quality in hilly Loess Plateau, with the organic matter
      content, infiltration coefficient and anti-scouring ability as the key
      indicators.

PMID- 16425460
TI  - Complaint data as an index of annoyance--theoretical and methodological issues.
AB  - Complaining constitutes one facet of all reactions to noise annoyance and is one
      way to cope with annoyance due to aircraft noise. In order to value and to
      establish the usefulness of complaint data as an index of annoyance, four
      questions need to be answered: Which factors lead annoyed residents to complain
      about aircraft noise or related issues? Which factors keep annoyed residents from
      complaining? Are the existing ways to handle annoyance adequate and efficient
      (e.g. keeping track of complaints, reaction to complains, kinds of complaint
      services)? Which are new ways to handle annoyance adequately and efficiently? In
      this paper a first attempt to answer these questions is made. Obviously,
      complaint data do not reflect noise annoyance in the surroundings of airports to
      the full extent as there are residents living in affected areas who do not
      complain, as well as residents living in areas with relatively low noise levels
      who complain. Also there is a large group of people who declare to be highly
      annoyed and yet, they do not lodge any complaint. Possible intervening factors
      are gathered that determine if an annoyed resident takes action and complains. It
      was found that noise levels per se are not the crucial factor for residents'
      decisions to complain or not to complain. Personal as well as feasibility factors
      play a vital role. Yet, the ongoing controversy on the relation between annoyance
      and complaint behaviour seems not resolved yet. However, complaint behaviour
      seems to be influenced by various aspects and complaint data consequently cannot
      be accepted as an accurate measure of public annoyance. Further research is
      required to address the preferred method of handling reaction to noise and the
      extent to which complaint itself helps with coping, for different groups of
      residents.

PMID- 16425461
TI  - [Sports shoes for children and adolescents].

PMID- 16425462
TI  - [Injuries from bicycling].

PMID- 16425463
TI  - A woman who excreted a tape-like substance. Diphyllobothriasis.

PMID- 16425464
TI  - Psychological distress and physical pain appear to have no short-term adverse
      impact on plasma HIV-1 RNA levels in patients on successful HAART.
AB  - PURPOSE: Previous studies have linked depression and stressful life events in HIV
      disease with a more rapid decline in CD4 count and progression to AIDS. However,
      the short-term effect of psychological and physical distress on HIV-1 RNA levels
      in patients on successful HAART has not been well studied. METHOD: Ten
      asymptomatic HIV-infected adults with suppression of viremia to <50 copies/mL on
      a stable HAART regimen for > or =6 months were studied. Participants donated
      blood every 2-3 days over a 3-4 month period for duplicate independent viral load
      measurements and drug level monitoring. At each time point, psychological
      distress was measured using the Mental Health Inventory-5 (MHI-5) and an 11-point
      numeric rating scale for emotional stress. Physical pain was assessed using an 11
      point numeric rating scale. RESULTS: All patients maintained successful viral
      suppression throughout the study. Twenty-six of 713 (3.6%) viral load
      measurements were >50 copies/mL. Psychological distress and physical pain were
      not associated with episodes of detectable viremia. CONCLUSION: Using frequent
      monitoring of HIV-1 RNA levels and patient ratings of mood, stress, and pain, we
      found that psychological distress and physical pain had no short-term adverse
      impact on HIV-1 RNA levels in highly adherent patients with stable suppression of
      viremia on HAART.

PMID- 16425465
TI  - [On the article "Radiotherapy in Eye and Orbital Tumors" (Klin Monatsbl
      Augenheilkde 2004; 221: 1033-1045)].

PMID- 16425466
TI  - ["Old wine in new skins"--were we not business management oriented before?].

PMID- 16425467
TI  - New electrodes for old: from carbon nanotubes to edge plane pyrolytic graphite.
AB  - Different types of carbon based electrodes have emerged over the last few years,
      significantly changing the scope and sensitivity of electro-analytical methods
      for the measurement of diverse targets from metal ions through gases to
      biological markers. This Highlight article shows how the use of carbon nanotube
      modified electrodes has led to a fundamental understanding of the location and
      nature of electron transfer processes on graphitic electrodes and to the
      realisation that edge plane pyrolytic graphite may represent, at present, an
      optimal electrode material of this type for electroanalysis.

PMID- 16425468
TI  - Selective decontamination of the digestive tract and ventilator-associated
      pneumonia (part 1).

PMID- 16425470
TI  - Patient education. Practical advice for avoiding hypothermia.

PMID- 16425469
TI  - Selective decontamination of the digestive tract and ventilator-associated
      pneumonia (part 2).

PMID- 16425471
TI  - Delayed unions of the tibia.

PMID- 16425472
TI  - Measurement of adverse events using "incidence flagged" diagnosis codes.
AB  - OBJECTIVE: To compare two methods for identifying adverse events using routinely
      recorded hospital abstract data in all public and private hospitals in Victoria,
      Australia. METHODS: Secondary analysis of data on all admissions in the period 1
      July 2000-30 June 2001 (n = 1,645,992) to estimate the rates of adverse events
      using International Classification of Diseases 10th Revision Australian
      Modification codes alone and in combination with an "incidence" data flag
      indicating complicating diagnoses which arise after hospitalization; rates of
      incidence and pre-existing adverse events, and rates for same-day and multi-day
      admissions. RESULTS: In total, 8% of all admissions were recorded with an adverse
      event. Use of ICD codes alone identified only 59% of the events identified using
      the combined method, giving a prevalence rate of only 5%. Incident cases, that
      is, those occurring in the index admission, represented 68% of identified adverse
      events. The adverse events incidence rate for multi-day admissions was
      significantly higher at 12%, compared with the same day rate of 0.4%. CONCLUSION:
      An "incidence flag" is essential to identify those adverse events for which a
      hospital has unambiguous responsibility. Using such a flag, secondary analysis of
      administrative data can provide hospital quality assurance programmes with a
      comprehensive view of all adverse events (not just "sentinel" events) at a
      reasonable cost and with more timely results than more intensive methods can
      achieve. Although the method is likely to underestimate the true rate of adverse
      events (in particular, by not capturing adverse events which only manifest after
      discharge), in this study of Australian hospitals, rates of adverse events were
      found to be similar to those derived from studies using manual review of patient
      records.

PMID- 16425474
TI  - What IRBs could learn from corporate boards.

PMID- 16425475
TI  - Balancing privacy protections with efficient research: institutional review
      boards and the use of certificates of confidentiality.

PMID- 16425476
TI  - Informed consent: practices and views of investigators in a multinational
      clinical trial.

PMID- 16425477
TI  - Autonomy and contraception.

PMID- 16425478
TI  - Motivations, understanding, and voluntariness in international randomized trials.

PMID- 16425480
TI  - Part I: what is the requirement for data sharing?

PMID- 16425479
TI  - Vulnerable subjects and Canadian research governance.

PMID- 16425481
TI  - Constructions of self: ethical overtones in surprising locations.
AB  - Little discussion has occurred in the health profession literature with respect
      to how the "self" is constructed, despite the imagination and attention it has
      garnered from philosophers and theorists in various other disciplines. Yet this
      subject has surprisingly ethical overtones for health professional education and
      practice. In this paper notions of the self are briefly considered and it is
      suggested that a narrative and dialogic view of self can contribute to insights
      about ethical practice in the health professions. Subtle issues with respect to
      how relationship and language may be used to wield power are revealed and
      discussed; and awareness about how such power is used in practice is highlighted
      as a crucial issue. The assumptions practitioners make with respect to
      constructions of self are ethically important and this topic warrants
      consideration in the medical humanities.

PMID- 16425482
TI  - Principled compromise and the abortion controversy.

PMID- 16425483
TI  - Poverty and inequality: challenges for the IAB: IAB presidential address.
AB  - This paper focuses on poverty and inequality in the world today. First, it points
      out how this topic is a main concern for the IAB. Second, it proposes 'new'
      theoretical tools in order to analyze global justice and our obligations towards
      the needy. I present John Rawls's denial that the egalitarian principle can be
      applied to the global sphere, his proposed weak duty of assistance, and his
      consideration of endemic poverty as essentially homegrown. In opposition, I focus
      on Thomas Pogge as representative of a cosmopolitan view who also holds a
      critical position towards the international systems which allow and cause
      poverty. I endorse the general normative proposal that defends every human being
      as an ultimate unit of moral concern, as well as the strategy of moving away from
      the charity model of bilateral aid to the realm of rights and duties. These ideas
      should redesign and broaden the normative and practical roles of institutions,
      and should also help provide a new approach on bioethical issues such as drug
      patenting or the imbalance in global research and neglected diseases.

PMID- 16425484
TI  - Global health and justice.
AB  - In Australia, Japan, Sweden, and Switzerland, the average life expectancy is now
      greater than 80 years. But in Angola, Malawi, Sierra Leone, and Zimbabwe, the
      average life expectancy is less than 40 years. The situation is even worse than
      these statistics suggest because average figures tend to mask inequalities within
      countries. What are we to make of a world with such inequal health prospects?
      What does justice demand in terms of global health? To address these problems, I
      characterize justice at the local level, at the domestic or social level, and at
      the international or global level. Because social conditions, structures, and
      institutions have such a profound influence on the health of populations, I begin
      by focusing attention on the relationship between social justice and health
      prospects. Then I go on to discuss health prospects and the problem of global
      justice. Here I distinguish two views: a cosmopolitan view and a political view
      of global justice. In my account of global justice, I modify and use the
      political view that John Rawls developed in The Law of Peoples. I try to show why
      an adequate political account must include three duties: a duty not to harm, a
      duty to reconstruct international arrangements, and a duty to assist.

PMID- 16425486
TI  - To know or not to know? Genetic ignorance, autonomy and paternalism.
AB  - This paper examines some arguments which deny the existence of an individual
      right to remain ignorant about genetic information relating to oneself--often
      referred to as 'a right to genetic ignorance' or, more generically, as 'a right
      not to know'. Such arguments fall broadly into two categories: 1) those which
      accept that individuals have a right to remain ignorant in self-regarding
      matters, but deny that this right can be extended to genetic ignorance, since
      such ignorance may be harmful to others, particularly those to whom one is
      genetically related (the 'harm to others objection') and 2) those which contend
      that, even if genetic ignorance is only self harming, it is not something to
      which individuals can rationally or morally claim to have a 'right' at all, since
      they defend their claims on autonomy-respecting grounds and ignorance is inimical
      to autonomy (the 'incoherence objection'). I argue that defenders of a right not
      to know have some plausible responses to the 'harm to others objection', they and
      their opponents reach an impasse in which both sides are left voicing concerns
      about the paternalistic implications of the other's point of view. I conclude
      that defenders of a right not to know would, therefore, advance their position
      further by analysing it in terms of values other than those of autonomy and
      rights.

PMID- 16425485
TI  - HIV international clinical research: exploitation and risk.
AB  - This paper aims to show that to reduce the level of exploitation present in
      (some) international clinical trials, research sponsors must aim to provide both
      an ex-ante expected gain in utility and a fair ex-post distribution of benefits
      for research subjects. I suggest the following principles of fair risk
      distribution in international research as the basis of a normative definition of
      fairness: (a) Persons should not be forced (by circumstance) to gamble in order
      to achieve or protect basic goods; (b) In cases where one party is gambling with
      basic goods and the other party is not, the distribution of benefits and burdens
      must be arranged so that they are of greatest benefit to the worst off; (c) In
      relationships where one party is gambling for basic goods and the other party is
      not, the party gambling for basic goods must be assured of some guaranteed
      benefits in addition to the chance of getting some practical benefits. These
      principles are applied to the case of HIV international research. I conclude that
      the research (as described) is mutually advantageous but still exploitative
      because the distribution of surplus benefits is unfair. It is unfair because
      research subjects are gambling with and for basic goods but they are not assured
      of a fair ex-post distribution of benefits. Principles (b) and (c) are not
      satisfied. Research participants are not accorded enough guaranteed benefits to
      outweigh the risks they undertake.

PMID- 16425488
TI  - End games: euthanasia under interminable scrutiny.
AB  - It is increasingly asserted that the disagreements of abstract principle between
      adversaries in the euthanasia debate fail to account for the complex, particular
      and ambiguous experiences of people at the end of their lives. A greater research
      effort into experiences, meaning, connection, vulnerability, and motivation is
      advocated, during which the euthanasia 'question' should remain open. I argue
      that this is a normative strategy, which is felicitous to the status quo and
      further medicalises the end of life, but which masquerades as a value-neutral
      assertion about needing more knowledge.

PMID- 16425487
TI  - Gaining face or losing face? Framing the debate on face transplants.
AB  - An American surgical team has announced its intention to perform the first human
      facial transplantation. The team has, however, invited further analysis of the
      ethical issues before it proceeds and in this paper we take up that challenge in
      seeking to frame the debate with a particular focus on the recipients of the
      transplant. We address seven related areas of concern and identify numerous
      questions that require answers or, perhaps, better answers. We start by examining
      the nature of the procedure and its intended benefits, why the procedure is being
      developed, and whether or not this should be viewed as experimental. Having
      concluded that this is experimental in nature, we then consider the broad
      question, who is the patient? Here we perceive difficulties in terms of the
      autonomy of the recipient, the unpredictable effects of receiving the transplant,
      and the role and influence of society. We conclude by asking whether the question
      should be 'whether or not?' rather than 'when?', particularly while the risks of
      losing face appear to far outweigh the likelihood of gaining face.

PMID- 16425489
TI  - Reuse of samples: ethical issues encountered by two institutional ethics review
      committees in Kenya.
AB  - There is growing concern about the reuse and exploitation of biological materials
      (human tissues) for use in research worldwide. Most discussions about samples
      have taken place in developed countries, where genetic manipulation techniques
      have greatly advanced in recent years. There is very little discussion in
      developing countries, although collaborative research with institutions from
      developed countries is on the increase. The study sought to identify and describe
      ethical issues arising in the storage, reuse and exportation of samples in a
      developing country. Research protocols presented to two Ethics Review Committees
      in Kenya during a period of two years were reviewed. A record was made of the
      protocol title, sample collected, request for storage, reuse or exportation and
      whether or not subject consent was sought. The findings indicated that about 25%
      out of the 388 protocols sought permission for reuse and only half of those
      actually informed subjects of the contemplated re-use. Less than 20% requested
      storage and again, about half of them sought consent from subjects. There is an
      indication that investigators do not see the need to seek consent for storage,
      reuse and exportation of samples. It is proposed that these issues should be
      addressed through policy interventions at both the national and global levels.

PMID- 16425490
TI  - Analysis of some Filipino perspectives on ethical issues in multi-country
      collaborative research: a case of deep listening.
AB  - The discussion on ethical issues, it is said, should not be confined to experts
      but should be extended to patients and local communities, because of the real
      need to engage stakeholders and non-stakeholders alike not only in carrying out
      any biomedical research project, but also in the drafting and legislation of
      bioethics instruments. Several local and inter-country consultations have already
      been conducted in furtherance of this goal, but there is much left to be desired
      in them. The consultations may have helped in articulating local principles, but
      not in making the instruments embody these principles. As such, instruments turn
      incompossible, i.e. the principles and actions they legitimate are not
      performable. In an ethnographic study conducted in the Philippines, for example,
      paragraphs 29 and 30 of the Declaration of Helsinki and CIOMS guidelines 8 and 15
      are construed as not only contradictory to one another but also to local
      principles. This problem can be solved by taking deliberate steps to ensure that
      consultations are grounded in ethnographic data about local principles, which the
      instruments would embody. A steering committee can be of help in gathering
      ethnographic data, in conducting consultations at the local level, and in
      providing a venue for discourse on various bioethical issues.

PMID- 16425491
TI  - A defense of shallow listening.

PMID- 16425492
TI  - Ethical commitment stimulates scientific insights.

PMID- 16425493
TI  - Ethical considerations in oocyte assisted reprogramming.

PMID- 16425494
TI  - Holistic systems and "delayed hominization" are incompatible.

PMID- 16425495
TI  - The supposed conflict between religion and science.

PMID- 16425496
TI  - Response to Catherine Althaus on heterologous embryo transfer.

PMID- 16425498
TI  - A defense of oocyte-assisted reprogramming.

PMID- 16425497
TI  - Washington insider: federal funding for embryonic stem cell research.

PMID- 16425499
TI  - Ordinary, extraordinary, and artificial means of care.

PMID- 16425500
TI  - Alternative medicine and the duty to employ ordinary means.

PMID- 16425501
TI  - Extraordinary care and the spiritual goal of life: a defense of the view of Kevin
      O'Rourke, O.P.

PMID- 16425502
TI  - The morality of tube feeding PVS patients: a critique of the view of Kevin
      O'Rourke, O.P.

PMID- 16425503
TI  - When medical treatment is no longer in order: toward a new interpretation of the
      ordinary-extraordinary distinction.

PMID- 16425504
TI  - The Catholic tradition on forgoing life support.

PMID- 16425505
TI  - A history of ordinary and extraordinary means.

PMID- 16425508
TI  - Beating burnout.

PMID- 16425506
TI  - Production of pluripotent stem cells by oocyte-assisted reprogramming: joint
      statement with signatories.

PMID- 16425509
TI  - Rhinolith: an incidental finding in a case of snoring.

PMID- 16425510
TI  - Sex differences in diabetes.

PMID- 16425511
TI  - Tube thoracostomy.

PMID- 16425512
TI  - Patient information. The health benefits of fiber.

PMID- 16425513
TI  - Common thyroid disorders. A review of therapies.

PMID- 16425514
TI  - A place at the table. Survey shows NPs commanding more serious salaries.

PMID- 16425515
TI  - Endometriosis: clinical assessment and medical management.

PMID- 16425516
TI  - Alcohol and the older adult.

PMID- 16425517
TI  - Nocturnal asthma in children.

PMID- 16425518
TI  - Type 2 diabetes. Real strategies for real life.

PMID- 16425519
TI  - Heel spurs and plantar fasciitis: an update on therapies.

PMID- 16425520
TI  - Current strategies in the management of lung cancer.

PMID- 16425521
TI  - First-line treatment for advanced non-small-cell lung cancer.
AB  - With best supportive care alone, patients with metastatic non-small-cell lung
      cancer (NSCLC) have a median survival of 4 to 5 months and a 1-year survival rate
      of approximately 10%. Trials carried out in the 1980s and 1990s comparing
      chemotherapy to best supportive care reported variable efficacy results; however,
      a pivotal meta-analysis of these data indicated that cisplatin-based chemotherapy
      provided a survival benefit in advanced NSCLC. In the past decade newer agents
      such as gemcitabine (Gemzar), vinorelbine, paclitaxel, and docetaxel (Taxotere)
      have all demonstrated activity in NSCLC as single agents; consequently these
      agents have been combined with cisplatin or carboplatin. Randomized phase III
      trials comparing these "newer" platin-based doublets have failed to identify an
      optimal platinum-based doublet therapy regimen. Though it is clear that
      chemotherapy is an appropriate treatment for many patients with lung cancer,
      there a sense in which the use of traditional chemotherapeutic agents has reached
      a therapeutic plateau. Increased understanding of cancer biology has revealed
      numerous potential therapeutic strategies, including targeting the epidermal
      growth factor receptor, protein kinase C, rexinoid receptors, and the
      angiogenesis pathway. The Eastern Cooperative Oncology Group study E4599
      comparing paclitaxel/carboplatin with/without bevacizumab is the first phase III
      randomized trial to show a survival advantage with the addition of a molecularly
      targeted agent to chemotherapy in the chemotherapy-naive patient population.
      Future studies will involve the evaluation of additional targeted agents plus
      chemotherapy as well as looking at combinations of these targeted agents alone or
      with chemotherapy.

PMID- 16425522
TI  - Adjuvant chemotherapy for resected non-small-cell lung cancer.
AB  - Because of the high rate of distant disease recurrence, the 5-year survival of
      patients who have undergone complete surgical resection of localized non-small
      cell lung cancer (NSCLC) is approximately 50%. Initial results from early studies
      of adjuvant postoperative chemotherapy reported an adverse effect of alkylating
      agent and older chemotherapy regimens on survival. Cisplatin-based combinations
      were the first to show a survival advantage. A 1995 meta-analysis of these
      studies suggested a 13% reduction in the hazard ratio for death (HR = 0.87),
      leading to a 5% survival benefit at 5 years. Still, these trials involved limited
      numbers of patients (N = 1,394), and the results failed to reach statistical
      significance (P = .08). Of the five largest subsequent randomized trials of
      platinum-based adjuvant therapy, three showed a significant survival advantage.
      Although it is impossible to determine the reasons for the differing outcomes of
      these studies, several key features distinguish them, and the data suggest that
      medically fit patients with resected stage IB or II NSCLC should be offered
      chemotherapy with a platinum/new drug combination.

PMID- 16425523
TI  - EGFR inhibitors in lung cancer.
AB  - Targeted therapies inhibiting the epidermal growth factor receptor (EGFR) have
      been introduced in the treatment of patients with advanced non-small-cell lung
      cancer (NSCLC). Many inhibitors of the EGFR have been developed, targeting either
      the extracellular receptor domain with antibodies or the intracellular tyrosine
      kinase binding domain with small molecules. The tyrosine kinase inhibitor (TKI)
      gefitinib (Iressa) was the first targeted drug to be registered for the treatment
      of NSCLC after failure of chemotherapy. Given concurrently together with platinum
      combination chemotherapy both TKIs gefitinib and erlotinib (Tarceva) failed to
      increase activity. Sequential targeted therapy after chemotherapy is currently
      being investigated further. Studies with the monoclonal antibody cetuximab
      (Erbitux) combined with chemotherapy are ongoing. Side effects of the small
      molecules are mainly skin rash and diarrhea, whereas the antibodies do not give
      diarrhea. Selection of patients, based on molecular markers and patient
      characteristics, has become an important issue for the further development of
      these drugs, given there is activity in a relatively small group of patients with
      NSCLC. Newer drugs inhibiting more than one receptor pathway are being
      investigated in order to find activity in a broader group of patients.

PMID- 16425524
TI  - Current issues in lung cancer screening.
AB  - Despite improvements in drug therapy, late-stage lung cancer remains routinely
      incurable. The field of screening for early lung cancer is a challenging, fast
      moving, cross-disciplinary area, not without controversy. The ideal situation is
      one in which we approach screening proactively to allow it to mature as a public
      health strategy. Spiral CT screening for lung cancer is a new and promising
      approach to thoracic imaging; it allows for a much more rapid and comprehensive
      evaluation of a structure than the original CT scan. In this review we will
      discuss issues inherent to the lung cancer screening process, including the value
      of smoking cessation strategies, the challenge with the rapid pace of
      developments in the field, cost concerns, consideration of biases in trial design
      (overdiagnosis, for example), overtreatment, and radiation risk. We discuss
      recommendations from several organizations, such as the US Preventive Services
      Task Force and the American Cancer Society.

PMID- 16425526
TI  - [Examination of ontogenetic-morphologic growth of cholinergic receptor system in
      isolated preparation of human trachea in vitro].
AB  - Morphologic growth of cholinergic bronchial respiratory system was examined at
      live and dead newborns. Tracheal smooth musculature was examined at 18
      experimental preparations taken by the autopsy after exiting from different
      factors. Samples were divided into three groups based on gestational weeks. First
      group: from 23-29 gestational weeks (immature, N=5); second group: from 30-37
      gestational weeks (premature, N=7); third group: from 38-41 gestational weeks
      (mature, N=6). Based on morphological examination of isolated preparations human
      trachea fingings are the following: in 23-29 week are found nerve endings with
      axo-axonal synapses mainly at ramification phase of lungs blood vessels net,
      without trachea bronchial innervations with axo-axonal synapses, and with
      perichondrial localization. In 30-37 gestational weeks axo-xonal synapses are
      found in between glands acinus's and vessels net, and also emphatic choline
      reactivity at lung ganglions: this suggests existing of cholinergic system at
      alive newborns. At 38-41 gestational weeks exists a wealthy nerve neuromuscular
      net in smooth tracheal musculature with different vesicles. Choline reactivity is
      emphasized peri and intrachondrial at lamina propria, at most around sensory
      glands and in smooth musculature. This suggests that there is no choline
      reactivity at epithelium and of existence of cholinergic system in tracheal
      bronchial smooth musculature.

PMID- 16425525
TI  - [HPV genotypes in repeated PAP II smears of group of women in Slovenia].
AB  - Molecular epidemiology studies have shown that some types of HPV are causally
      linked with precancerous lesions of cervix and invasive cervical cancer. In our
      study, we enrolled HPV infected women with repeated Pap smears (Pap II) in
      Slovenia and verified HPV infection. HPV genotypes were determined using the
      method of enzyme restriction of PCR products amplified with group-specific
      oligonucleotide primers PGMY11/PGMY09 (PCR-RFLP) and restricted with seven
      different restriction endonucleases. In women aged < or = 30 years we detected 21
      different types of HPV and a very high percentage (76.5%) of multiple infections.
      In women aged > 30 years we detected 11 different types of HPV and found the
      predominance of a single HPV type infection (85%). In women aged < or = 30 years
      the most frequent infections, and also equally distributed (10.50%), were those
      with high-risk types HPV16 and HPV73 and with a probably high-risk type HPV26. In
      women aged > 30 years most frequent infections, and also equally distributed
      (18.20%), were those with high-risk type HPV16 and probably high-risk type HPV53.
      The HPV genotypes were classified by the newest classification according to their
      oncogenic potential and we have referred the presence of newly high-risk and
      probably high-risk types of HPV at observed population of women in Slovenia.
      Using group-specific primers PGMY11/PGMY09 and seven restriction endonucleases in
      PCR-RFLP method for genotypization of HPV we identified single types of HPV
      included in large percentage of multiple infections of young women with repeated
      Pap II smears.

PMID- 16425527
TI  - [Asymptomatic isolated microhaematuria--a reason for concern?].
AB  - Nephrologists and urologists are frequently faced with patients with asymptomatic
      isolated microhaematuria (AIMH). This entity is defined as the presence of more
      than 5 red cells/uL in the sediment of first morning urine, in the absence of
      symptoms by the urinary tract and in the absence of proteinuria. From 201
      children who were referred on the clinical examinations on the Pediatric Clinic
      in Sarajevo under the diagnosis haematuria in period from 01/01/1997 until
      31/08/2002, 87 had AIMH. Age of life was from 0 to 16 years (mean 8 years).
      Fourteen children (16.1%) had a hypercalciuria, 10 (11.5%) had a state after
      purpura Henoch-Schonlein nad scarlatine, while 6 (6.9%) had glomerulopathy. Five
      children (5.7%) had anomalies of urinary system, 5 (5.7%) had evidence of
      nephrolithiasis, while 4 (4.6%) had asymptomatic urinary tract infection. Cause
      out of urinary system was found in 29 children (33.3%) and for 14 children
      (16.1%) etiology remained unknown. Transient microhaematuria was noted in 43
      children (49.4%), recurrent in 37 (42.5%) and persistent in 7 (8.1%). Renal
      biopsy was performed in 5 children (5.7%) because of indications of glomerular
      disease and all of them had glomerular lesions. Sixty nine children of these 87
      were followed up from 2 to 11 years (mean period of 3 years) and none of them
      developed hypertension or renal impairment. Most patients who have AIMH do not
      have clinically significant glomerular pathology and they don't need renal
      biopsy, but only periodic follow up. Any degree of proteinuria accompanying
      haematuria should be fully investigated, as proteinuria is often a sign of
      serious renal disease.

PMID- 16425528
TI  - [Permanent double-lumen central venous catheters--replacement for arteriovenous
      fistula].
AB  - INTRODUCTION: The adequate vascular access in the patients on chronically
      hemodialysis treatment is very importance element in patient feel secure, and
      medical staff in hemodyalisis centre. The aim of this work is to examinee
      possibility of the use of permanent double lumen central venous catheter
      (PermCath) in patients with inadequate vascular access. PATIENTS AND METHOD:
      PermCath has been placed with local anesthesia in chirurgical room. Eight
      catheters was application in vena subclavia (three of them in links vena
      subclavia and six in right vena subclavia) and 26 in vena jugularis internal (for
      of them in links vena jugularis and 22 in right vena jugularis. The catheters
      were long 19 cm (26 catheters) and 23 cm (nine catheters). The catheters has been
      placed in 35 patients on chronically hemodialysis program, eight mean and 27
      women, average age 56.03 +/- 16.52 (19 to 77 years). The causal chronically
      kidney disease has been diabetes mellitus in 12 (34.29%) patients, chronically
      pyelonephritis in eight (22.86%) patients, polycystic kidney disease in five
      (14.29%) patients, chronically glomerulonephritis in three (8.57%) patients and
      seven (20%) patients with other diseases. RESULTS: The catheters has been placed
      average 233.55 +/- 303.58 days (9 to 1256 days). For three catheters have not
      registered wail the patients was from another hemodialysis centre. In four of
      patients were registered catheter sepsis episodes. In two of them catheter was
      treated with adequate doses of antibiotics since we have performed adequate and
      systemically antibiotics in lumen of catheter. The isolated bacteria from
      microbiological examination were: Enterococcus species and Pseudomonas species.
      Van catheter was isolated, and in microbiological examination from blood were
      registered Acinobacter species and Enterobacter species. A van patient past away
      and microbiological examination shown Staphylococcus species. CONCLUSION:
      PermCath is very security permanent vascular access in the patients with loss
      construction arteriovenous fistula. The catheter in the patients who has been not
      adequate arteriovenous fistula, and with adequate treatment he has exchange for
      arteriovenous fistula.

PMID- 16425529
TI  - [Sepsis--clinical parameters of recognition and differentiation].
AB  - INTRODUCTION: Even today, early recognition of sepsis remains a great problem,
      requiring the search for clinical symptoms and signs with predictive features.
      AIM: to define the number of days of disease till hospitalization and value of
      some clinical signs in recognition and differentiation of patients with
      monomicrobial (M.A) gram positive and gram negative sepsis. PATIENTS AND METHODS:
      200 patients with clear clinical and laboratory signs of sepsis, septic shock and
      monomicrobial aerobic bacterial isolate were included randomly. Patients are
      divided into two equal groups. RESULTS: patients with gram negative (m.a.) sepsis
      are hospitalized earlier relating to patients with gram positive sepsis (X2=
      24,345; p< 0.001). Significance of differences in two basic groups of sepsis is
      the most evident for heart murmur (t=6,703; p<0,0001), shivers (t=3,313;
      p<0,001), afebrility (t=16,148; p<0,001), fatigue-exhaustion (t=4,472; p<0,001),
      pulmonary manifestations (t=3,497; p<0,001). CONCLUSIONS: results of
      investigation show the recognition of clinical symptoms and signs of sepsis,
      which enables the differentiation between gram positive and gram negative.
      Initially, this provides clinicians with a greater therapeutic reliability.

PMID- 16425530
TI  - [Presence of high risk human papilomaviruses (HPV) in the low grade cervical
      lesion].
AB  - Low grade squamous intraepithelial lesion (LGSIL) and atypical squamous cells
      undetermined significance (ASCUS) are the most frequent verified cellular
      abnormalities. Their management are still highly controversial mostly caused by
      uncertainty about their histology and nature of originate. Detection of HPV DNA
      in the absence of cytological abnormalities can also indicate presence of high
      grade cervical intraepithelial neoplasia (CIN). The aim of this study was to show
      the association of the benign cellular changes, ASCUS and LGSIL with oncogenic
      types of HPV and to prove the necessity of more intensive screening of this group
      of patients. Cytology and pathomorphology analyses were performed first.
      Identification of the presence of human papiloma virus was carried out by the
      Digene Hybride Capture II test for all patients. Identification of different HPV
      types for the particular number of patients was carried out by RFLP (Rsetriction
      Fragments Length of Polymorphism). Out of the 101 patients in the first group 92
      (91,08%) were HPV positive, and 41, 58% had no cellular abnormalities, ASCUS or
      LGSIL. Out of 509 patients of the second group 26.92% were positive for HRHPV,
      and 78,97% of them had no cellular abnormalities, ASCUS or LGSIL. HPV 16 was
      detected in 27.36% (ASCUS/LGSIL) of low risk cervical lesion of the first
      examined period. CONCLUSION: The combination of smears with the detection of high
      risk HPV types increases the triage sensitivity especially at patients with mild.

PMID- 16425531
TI  - [Subarachnoid hemorrhage: neurosurgical treatment modalities and etiological
      analysis].
AB  - INTRODUCTION: The subarachnoid hemorrhage (SAH) is excess presence of blood in
      the subarachnoid space. The most frequent cause of SAH is cerebral aneurysm
      rupture and neurotrauma. The treatment strategy is specific for the different
      forms of SAH but all therapeutic options are based on the prevention of secondary
      ischemic brain injury generating after initial hemorrhage. OBJECTIVE: To point
      out the varieties of SAH etiology and different modalities of its treatment,
      especially presenting the aneurismal SAH. PATIENTS, METHODS AND RESULTS: The
      retrospective-prospective study was performed at the Department of Neurosurgery
      in Sarajevo (DNS). Over a span of two years, from January 1st 2003 to December
      31st 2004, 161 patients with etiologically different SAH were treated. The higher
      number of patients was treated during 2004 compared with a year before,
      respectively 101 and 60 patients. Totally, eighty three patients were operated on
      (52%, 83/161). The surgery was performed in 60% (61/101) of cases in the second
      year but only 37% in the first year of study (22/60). The most frequent cause of
      SAH was the rupture of cerebral aneurysm (48%). The other causes were trauma
      (28%), brain arteriovenous malformations (4, 3%) and hypertension with
      atherosclerosis (1.8%). The cause is not found in 18% of cases (29/161) and this
      SAH category is defined as an idiopathic SAH. A total of 64 patients with
      ruptured aneurysms were operated on by the author (KD) during two years 17 in
      2003, and 47 in 2004. DISCUSSION: We use the defined treatment protocols for the
      different forms of SAH which are based on current knowledge and particulars of
      locality aiming to decreased possibilities of repeated bleeding and delayed
      ischemia. The higher number of patients with aneurysmal SAH compared to those
      with traumatic SAH was admitted. The reason for this is the fact that systematic
      management of patients with cerebral aneurysms in Bosnia and Herzegovina has been
      doing exclusively in our Department. CONCLUSION: The number of treated patients
      with SAH, especially aneurismal SAH, is significantly increased in DNS during two
      last years. Our patients received the standard and current treatment which
      implies micro neurosurgery and conservative care at the separate Neurosurgical
      intensive care unit. The introduction of endovascular neurosurgery and developing
      of neuroanesthesia as a subdiscipline is expected to increase the quality of our
      serves.

PMID- 16425532
TI  - [Infants feeding practice in first six month in Tuzla canton].
AB  - OBJECTIVE: To investigate the infants feeding practice in first six months in
      Tuzla canton. METHODS: Observations of feeding practices in first six months of
      infants life, born in Obstetrics and Gynecology Department in Tuzla in period May
      September 2004 who weighted more than 2500 gm and over 37 weeks gestation age.
      Dates were collected by standardized questionnaire mailed to 493 mothers from 13
      regions in Tuzla canton. With questionnaire we mailed the explanatory letter with
      investigations detail. RESULTS: Exclusive breast feeding at first 3 month was
      very high reaching from 74.4% in 1 month, 62.3% in 2 month and 50.9% in 3 month
      of life. After third month exclusive breast feeding was decreasing and reached
      12% at sixth month. Predominant breast feeding was reaching from 13.2% at first
      month, 27.6% at fourth month and 20.7% at sixth month. Breast feeding and
      complementary feeding before six month was very low, 1% in first month reaching
      47.7% in sixth month. Bottle feeding rate was 11.4% in first month and 20% in
      sixth month of infant life. CONCLUSION: Infants feeding practice in first 6
      months was inadequate according to WHO recommendation, exclusive breast feeding
      for first six months. Breast feeding initiation rate was high but lack of mothers
      support after discharge and many barriers discourage exclusive breast feeding of
      infants in first six months in Tuzla canton.

PMID- 16425533
TI  - [Hematological-biochemical tests in patient with migraine].
AB  - Migraine is periodical disorder which is characterized by recurrent headache
      seizures different in intensity, frequency and duration. Amylases L-1,4 glycol:
      gluckanohidrolises, (EC.3.2.1.1) are enzymes from hydrolase's group which
      dissolve starch meaning glycogen. Activity of amylases in serum grows: at acute
      pancreatitis, at carcinoma of pancreas, heavy necroses of pancreas. Total number
      of examinees was 92 out of which 45 were male (48.9 %) and 47 female or 51.1 %.
      Average age of the examines was 42.9. Neuroticism scale which was tested by
      Cornell scale was 55,03. Out of the total number of examinees 30 or 32,6 were non
      smokers while 62 or 67,4 % smoked regularly. The aim of this work is to perform
      hematological-biochemical test of blood in patients with migraine. In the
      beginning of this research it was planned for all the patients to have
      hematological blood test done (sedimentation of erythrocytes, trombocytes,
      complete blood test and differential blood test) and biochemical blood test
      (hepatogram, transamynase, amylase, Lactal dehydrogenase, Alkalic phosphatase,
      ferrum in serum, Glucose, Cholesterol, Calcium and Phosphorus in serum. After
      reviewing the received values of hematological and biochemical tests, all values
      were within the borders of normal values. Amylases had higher values at 49 or
      53,3 % of patients, and 43 or 46,7 % of patients had normal values of amylases.
      Normal values of amylases are to 220 U/l measured by I.F.C. at 37 degrees C.
      Medium value in tested group is 219.09. It means that every second examinee had
      increased values of amylase in blood; there is no statistics difference of
      amylase value between sexes.

PMID- 16425534
TI  - [Suicidal and parasuicidal behaviour].
AB  - Subject of the study is suicidal and parasuicidal behaviour in B&H in the period
      1992-2004 in relation to transition, anomie and structures of suicidal
      personalities. METHOD: Two self-destructive groups (in 2001 and in 2005) were
      tested in B&H. The test group consists of n = 125 subjects who had suicide, and
      control group consists of n = 125 persons with parasuicidal behaviour. WE USED:
      GDL, EPQ, HAMD and Pluchic's test in a longitudinal study stratified by the
      seriousness of suicide and quality of parasuicide. RESULTS: Self-destructivity
      has been increasing in B&H. Socio-demographic data of the suicide are: gender =
      73.3 +/- 2.5 (m) 26.7 +/- 2.7 (f), broken family = 34.4 +/- 4.8, migration = 52.2
      +/- 3.2, heredity = 46.7 +/- 2.0 and parasuicide: gender = 47.8% +/- 5.2(m), 26.7
      +/- 2.7(f), broken family = 41.1% +/- 5.2, migration = 54.4% +/- 4.6, heredity =
      41.3 +/- 2.8. EPQ in suicide is: M +/- SD--neuroticism = 16,73 +/- 7.03,
      psychosis = 18,21 +/- 6.64, and in parasuicide extroversion = 15,37 +/- 4.21 and
      Lay-scale = 13,95 +/- 3.37, and significance p<0.01. HAMD is increased in
      suicide: H +/- SD: depression: 2.99 +/- 1.21, emotion of guilt = 2.19 +/- 1.14,
      suicide = 3.91 +/- 1.19, early insomnia = 2.11 +/- 1.21, anxiety = 1.93 +/- 1.21
      with p<0.01, and in parasuicide: hypochondria = 1.77 +/- 0.95, depersonalization
      = 1.71 +/- 0.65, and O-K-signs = 1.59 +/- 0.79 with p<0.01. Pluchic's test
      separates basic emotions, and all is gathered by matrix of discriminative
      function. CONCLUSION: High level of self-destruction in suicidal and parasuicidal
      behaviour is proven in the study. Suicide shows faster self-destruction and a way
      of suicidal end, and parasuicide slower destruction with postponing the suicidal
      crash. Sign of suicide and parasuicide can be found in both groups of respondents
      and the ways of expression are different, but definite in suicide.

PMID- 16425535
TI  - [Segmental and bisegmental resections of liver in a treatment of malignant
      neoplasms].
AB  - The news in understanding intrahepatal anatomy, such as radiology contemporary
      technology making easier segmental and bisegmental access to hepatal resection.
      This access comprises resection of isolated anatomical segments or a sector of
      liver which is depends of magnitude of intrahepatal pathological process. After
      segmental or bisegmental resection of liver, patients were analysed in the period
      from 15 and 30 days after the operation. Analysis of patients from this period
      comprise: localisation of tumour in relation on segments, liver test and follow
      up, technique of resection, intraoperative stream, the period of operation, blood
      follow up through v. portae, blood loss and quantitative and qualitative analysis
      of postoperative complications. RESULTS: between January 2000 and March 2005,
      sixty two subject were analysed that have been operated on our clinic (segmental
      or bisegmental resection), because of the metastatic process of liver and
      hepatocellular carcinoma of liver (HCC). Hospital mortality was 2.1%, with most
      often mortality in patients with HCC and cirrhosis of liver. High of morbidity
      from this period were 19,8%. Need for transfusion of blood (fresh erythrocytes)
      were 1,2 +/- 0,5 U. Patients with HCC had more needs from blood transfusions
      contrary patients without HCC; 2,9 +/- 1,4 contrary 0,7 +/- 0,28 U (p<0,05).
      Recidivism of malignant process in hepatal margin were 2,7%. CONCLUSION:
      Segmental hepatal resection is very accurate technique which makes possible
      complete resection of tumour and in the same time preservation of healthy liver
      parenchyma. Segmental hepatal resection is especially useful for patients with
      HCC and patients with recidivism or progress of primary process.

PMID- 16425536
TI  - The relationship between the serum prostate specific antigen and whole body
      scintigraphy in prostate cancer patients after prostatectomy.
AB  - BACKGROUND AND AIM: Bone metastases are of the most frequent in prostate cancer.
      Serum prostate specific antigen--PSA has been suggested as an accurate means of
      monitoring prostate cancer. Whole body scintigraphy are currently the most widely
      used diagnostic procedures for metastases to the bone, the most common site of
      distant tumor spread. Aim of the study was to determinate relation between PSA
      level, number of metastases and 99mTc- MDP (methyl-diphosponate) uptake in
      patients with previous prostatectomy for prostate cancer. PATIENTS AND METHODS:
      Study enrolled 15 patients after previous prostatectomy for prostate cancer
      (histologically proven). Standard whole body scintigraphy (WBS) was performed 3
      hours after intravenous application of 740 MBq 99mTc-MDP. Total PSA was measured
      by MEIA-Microparticle Enzyme Immunoassay. RESULTS: Group 1: 12/15 (80%) patients
      were with WBS detected metastases. Correlation of PSA level and number of
      detected bone metastases was good (r=0.79). Correlation of PSA level and uptake
      intensity of 99mTc-MDP (score 3) was positive and significant (r=0.706).
      CONCLUSION: PSA values were highly predictive for WBS results. PSA values
      correlated well with number of metastases. We propose no WBS in patients with
      normal PSA level. WBS is a sensitive diagnostic tool for detecting prostate
      cancer metastases to bone. PSA levels is good and simpler marker for disease
      progression, but that neither technique in isolation gives complete accuracy.

PMID- 16425537
TI  - [Botulinum toxin in spasm treatment in adults].
AB  - Botulinum toxin (BTX) is a powerful neurotoxin which blocks cholinergic
      transmission at the neuromuscular junction. Judiciously applied it can reduce
      local muscle over activity while maintaining the strength in other muscles. For
      focal or segmental dystony it has been a medication of choice. Refined botullinum
      toxin A being applied in affected groups of muscles weaker power of contraction.
      Basic mechanism which weaker contraction remands the same. Controlled trials have
      provided evidence of the effectiveness of BTX both in reducing spasticity itself
      and in achieving functional gain. The guidance given here to clinicians involved
      in the management of spasticity covers the types of patient suitable for
      treatment using BTX, the appropriate dosage, and the necessary follow-up
      procedures and documentation.

PMID- 16425538
TI  - [Post traumatic stress disorder in developmental age].
AB  - This paper has been designed to provide an overview of research results
      concerning the impact of war stress on the genesis of psycho trauma in
      developmental age. The objective was to assess the effectiveness of psychotherapy
      in concrete clinical cases. In particular, the prognosis of psycho trauma in the
      given sub-population is discussed, while recognizing the generally accepted
      premise that each person in developmental age who has been exposed to severe
      stress is psycho traumatized. A comparison is made with other research results
      available in the literature dealing with the subject of war psycho trauma. A
      particular emphasis is placed on the genesis and specificity of manifestation of
      psycho trauma in adolescents who were actively involved in the army during the
      war. The excerpts from the adolescent soldiers' diaries are intended to show in
      the original form the mental process of elaborating psycho traumatic experience
      transfer. The paper ends with the conclusion that professionals who work in the
      area of mental health protection should pay greater attention to so-called trans
      generational trauma.

PMID- 16425539
TI  - [Antidepressives and antidepressive interactions with other drugs].
AB  - During the therapy with antidepressive agents, for the reason of its duration,
      numerous drug-drug interactions may occur. Antidepressive agents inhibit P450
      enzyme activity and interfere with other drug metabolism. Many interactions are
      acceptable from the clinical point of view, and some are seriously dangerous
      indicating a need for their better knowledge. The aim of this work is to point
      out the possible interactions between antidepressive agents and other drugs.

PMID- 16425540
TI  - [Treatment of Pseudomonas aeruginosa in cystic fibrosis in a child].
AB  - The report deals with the case of a 10-year-old girl with chronic cystic
      fibrosis. She has been repeatedly treated at the hospital. She has been
      hospitalized due to respiratory deterioration. Cystic fibrosis is a rare disease,
      inherited autosomaly recessively, but is very complex in terms of diagnostic and
      treatment. Fibrosis is the formation of scar tissue due to injury or long term
      inflammation. The diagnosis is confirmed based on a clinical picture of the
      child, measure of Chloride in the sweat, chest X-ray, CT thorax, laboratory
      findings--genetic confirmation CFTR genes. The diagnosis is originally set when
      she was 4 years old. She is now admitted due to a deterioration of the main
      disease. Five days before the admission, the girl had a higher bodily
      temperature, cough and difficult breathing. Due to the deteriorated general
      condition and the respiratory insufficiency and respiratory acidosis in blood gas
      analysis, the girl was intubated and put on the complete mechanical ventilation
      (IPPV). Since the girl is a chronic patient with bronchiectasie chronic walls of
      bronchi changes full of the mucus, who is not responding to conservative
      treatment (antibiotics), therapeutic and diagnostic flexible bronchoscopy had to
      be performed, resulting in a gram-negative bacteri Pseudomonas aeruginosa--a
      typical bacteri for chronically sick C. F. patient. Pseudomonas aeruginosa is
      typically acquired in early childhood. This bacteria is giving progressive lung
      disease and often aggravates morbidity and mortality. So the main thing as a
      respiratory management is prevention of lung infection with this bacteria. A
      Pseudomonas therapy was prescribed according to the sensitive antibiogram,
      (Garamycin). Antibiotics are crucial to treating cystic fibrosis lung infections.
      Therapy with an amynoglicoside in combination with a B-lactam or a quinolone
      antibiotic is standard. It is a difficult to deliver a high doses at these
      antibiotics via the iv. route without significant systemic adverse events
      (otoxicity and nephrotoxicity). A reformulation of the aminoglycoside antibiotic
      tobramicin or garamycin therapy is solution for inhalation. To be well
      established infections the suppression of Pseudomonas aeruginosa has been shown
      to lead to decreasing same bacteria and benefits lung function from antibiotic
      therapy in a way that can be maintained over extended period. During bronchoscopy
      was given locally on changes mucous pulmozyme (to destroy a very hard mucous) and
      garamycin. So, after taking out a lot of mucus, it was later continued
      spontaneously. Control chest x ray and blood gas analysis are now very improved.

PMID- 16425541
TI  - [Atypical manifestations of celiac disease in an adult woman].
AB  - Celiac disease is intolerance to gluten that classically produces chronic
      diarrhea with a picture of malabsorption and a total villous atrophy. These
      elements regress completely in a sequential way under a prolonged gluten-free
      diet. We describe a case of a 35-year-old woman affected by celiac disease who
      presented atypically, with features including hypoproteinaemia (38g/L) with
      dominant hypoalbuminaemia (12g/L), weight loss, strong psychoneurotic component
      and amenorrhoea. These manifestations for the first time were diagnosed as
      irritable bowel disease and after immunology diagnostic as celiac disease.
      Current research on celiac disease has pointed out the biologically significant
      role of antigliadin antibodies IgG and IgA and antibodies to tissue
      transglutaminase (tTg).

PMID- 16425542
TI  - [Papillary carcinoma of the thyroid gland].
AB  - Presented is the case of 13-year old girl with asymptomatic nodular goitre, cold
      in scintigraphic image. Already done tests include: hormonal status, ultrasound
      scan, thyroid gland scintigraphic imaging and computerized tomography (CT) of the
      neck. Consiliuin indicated partial operative treatment, and patho-hystological
      diagnosis (PHD) papillary carcinoma. Consequently total thyroidectomy has been
      done.

PMID- 16425543
TI  - Brain mapping of visual evoked activity--topographical and functional components.
AB  - Electroencephalographic (EEG) and evoked activity can be recorded non-invasively
      in order to monitor human brain activation online. Electrical fields are
      generated by large intracranial neural populations and spread to the scalp
      through volume conduction. All measured signals depend on the location of the
      recording and reference electrodes. Simultaneous recordings from many scalp
      positions allow for a topographical assessment of the complete electrical fields
      of the brain and avoid problems typically seen with time series analysis. The
      present contribution will illustrate the fundamentals of topographic mapping of
      human electrophysiological brain activity as well as quantitative analysis
      methods. Visual evoked potential data obtained in a group of 12 healthy adults
      are presented. We will focus on the definition and identification of evoked
      components that represent steps in visual information processing. In addition,
      the application of statistical data reduction techniques are described, and the
      results of functional components which are related to experimental variations are
      discussed.

PMID- 16425544
TI  - Psychiatric morbidity in dementia patients in a neurology-based memory clinic.
AB  - The behavioral and psychological symptoms of dementia (BPSD) often present major
      problems for patients and their caregivers. In the past, neurologists paid less
      attention to such symptoms than to the cognitive symptoms of dementia. This
      prospective study investigated the prevalence of psychiatric morbidity in a
      neurology-based memory clinic and the stress of caregivers. Our patients with
      dementia were found to have a high prevalence of BPSD. The most frequent were
      anxiety, apathy, and delusion; the most distressing to caregivers were agitation,
      anxiety, delusion, and sleep disturbance. Using Clinical Dementia Rating (CDR),
      we compared BPSD between patients with mild dementia and those with moderate
      dementia. Only hallucinations and agitation were different significantly.
      Moderate dementia patients experienced these symptoms more frequently. The high
      prevalence of these symptoms might be explained by the fact that the cognitive
      symptoms were neglected or no enough information were received by many family
      members of patients with dementia until their own life quality was interfered and
      then they began to seek medical help. These symptoms and their effect of
      caregiver distress can be effectively reduced by pharmacologic and
      nonpharmacoloic managements, caregiver-focused training and education. They can
      be better approached by assessing neuropsychiatric symptoms regularly, educating
      the general population better, and treating these patients earlier.

PMID- 16425545
TI  - Depressive symptoms following ischemic stroke: a study of 207 patients.
AB  - Depression is a frequent and important problem for patients who have experienced
      strokes. The purpose of this study was to assess the prevalence of depressive
      symptoms, their clinical correlations, and the effects of depressive symptoms on
      stroke recovery. A consecutive cohort of 207 ischemic stroke patients with a mean
      age of 64 years, were studied for ascertaining any correlation between potential
      risk factors and the incidence of post-stroke depression (PSD). Depressive
      symptoms were relatively common (34.3% Hamilton depression rating scale > 10),
      but the prevalence of severe depression (HDRS > 17) was only 7.7%. Patients with
      depressive symptoms were more likely to be female, have a family history of
      depression, and a poor functional outcome. There were no significant differences
      between depressive symptoms and age, marital status, location of stroke lesion,
      and duration after stroke onset. Our findings indicate that depressive symptoms
      occurred in about one third of post stroke patients. There is a negative
      correlation between depressive symptoms and functional status of the patients.

PMID- 16425546
TI  - Hypertensive encephalopathy involving the brainstem and deep structures: a case
      report.
AB  - Hypertensive encephalopathy rarely presented with widespread edema in the
      cerebral white matters, deep structures and whole brainstem. A 80-year-old woman
      manifested as high arterial blood pressure, visual disturbance, severe headache,
      nausea, and vomiting. T2-weighted and fluid-attenuated inversion recovery
      magnetic resonance imaging showed high signal-intensity lesions in the cerebral
      white matter, cerebellum, basal ganglia, thalamus, and brainstem. Diffusion
      weighted brain MRI did not show hyperintense signals in these lesions. These
      findings suggested the pathological basis of vasogenic edema. After control of
      hypertension, clinical symptoms and these edematous lesions on MRI gradually
      reduced.

PMID- 16425547
TI  - Witzelsucht after right putaminal hemorrhage: a case report.
AB  - Witzelsucht is a tendency to tell inappropriate and poor jokes. It usually occurs
      after a focal lesion involving orbitofrontal cortical or paramedian thalamic
      regions, especially on the right side. Here we report a 56-year-old man
      developing witzelsucht and hypersexuality after a right putaminal hemorrhage. The
      hematoma extended to the sublenticular part of posterior internal capsule and
      mesencephalon. The hemorrhage might have disconnected the fibers in the ascending
      reticular systems, and the fibers between paramedian thalamus and orbitofrontal
      cortex, and thus could be responsible for the patient's rare clinical
      manifestations.

PMID- 16425548
TI  - Cerebral hemosiderosis as a causative factor of vascular parkinsonism.
AB  - Secondary parkinsonism has comprised about 20 to 40 percent of all parkinsonism
      patients in movement disorders clinic. Most of them are induced by certain
      medications. About 5 to 10 percent of these patients are caused by sudden
      vascular events, who suffer from their parkinsonism abruptly, and usually of aged
      people with quite apparent stroke risk factors. Hemosiderosis was only
      occasionally reported as a causative factor in patients with parkinsonism, who
      presented with an insidious onset parkinsonism and a progressive supranuclear
      palsy-like clinical picture. We encountered two patients with stroke-related
      parkinsonism, whose high resolution MRI image showed apparent cortical or
      intraparenchymal hemosiderosis, although Binswanger type white matter change was
      also noted. Intracerebral hemosiderosis that manifests clinically as vascular
      parkinsonism might be much more frequent than we thought.

PMID- 16425549
TI  - General paresis with reversible mesial temporal T2-weighted hyperintensity on
      magnetic resonance image: a case report.
AB  - We report a patient with general paresis, whose magnetic resonance image (MRI)
      showed a T2 high-intensity lesion in bilateral mesial temporal regions. Serum
      rapid plasma reagin test showed reactive at 64 dilutions and serum Treponema
      pallidum haemagglutination test was 1:20480. Cerebrospinal fluid analysis showed:
      RBC 111/mm3, WBC 8/mm3, Venereal Disease Research Laboratory reactive at 1
      dilution and protein 60 mg/dl. His neuropsychiatric symptoms recovered gradually
      after penicillin treatment two months later. Repeated MRI revealed resolution of
      the bilateral mesial temporal lesions. We demonstrated the first Taiwanese
      patient with general paresis whose clinical improvement was associated with the
      disappearance of the temporal lobe MRI abnormality. The diagnosis of
      neurosyphilis must be considered when MRI shows mesial temporal lesions. MRI may
      be used to predict prognosis in patients with general paresis.

PMID- 16425550
TI  - [Diagnosis of multiple sclerosis].
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of
      the central nervous system. The disorder displays marked clinical heterogeneity.
      In certain cases, making diagnosis can be challenging. Diagnosis of MS has become
      more important in the era of treatments that change the natural history of the
      disease. Several general diagnostic principles are useful to guide the diagnostic
      approach to MS. Clinically, MS requires neurological problems associated with
      objective abnormalities. Certain basic principles, first outlined by Schumacher
      et al. (1965) are still pertinent. Poser et al. (1983) have further modified the
      criteria using data derived from clinical evaluation and laboratory studies,
      including cerebrospinal fluid analysis, evoked potentials, and imaging studies.
      Poser criteria have long been familial for most neurologists. The most recent
      addition to our diagnostic armamentarium are the McDonald criteria (2001), which
      are the first attempt to incorporate standardized MRI criteria into the MS
      diagnostic process. The most innovative use of MRI to support an MS diagnosis is
      dissemination of demyelination can be demonstrated by MRI alone, in the absence
      of any new clinical attacks. Diagnosing MS by such sensitive MRI criteria will
      occur more quickly than waiting for a second clinical event. This has added some
      sensitivity, some controversy, and a lot of confusion. The application of the new
      criteria on Asian MS patients remains to be validated. Each of the criteria will
      be discussed, with major emphasis on the McDonald criteria.

PMID- 16425551
TI  - [Neurological diseases in late 19th century Taiwan--medical reports of the
      Chinese Imperial Maritime Customs].
AB  - Western medicine was introduced to Taiwan in 1865 when Dr. James L. Maxwell, a
      missionary doctor of the English Presbyterian Church, established a hospital in
      nowadays Tainan. The period of the missionary medicine lasted for over 30 years
      until Japanese took over. During this period, however, official records of
      diseases in Taiwan that were based on Western medicine were scanty or not
      available. Fortunately, port surgeons stationing respectively in Tamsui and
      Kelung in the north and in Takow and Taiwan-fu in the south reported semi
      annually diseases seen in the ports, foreign communities and missionary hospitals
      that they volunteered to work. The diseases reported by port surgeons were either
      cases or summary of cases with classification and statistics. Their medical
      reports covered from 1871 to 1900. The data show that neurological diseases
      and/or disorders in the late 19th century Taiwan were uncommon, comprising only 2
      3% of total diseases. The data further show that common neurological diseases
      were leprosy, opium smoking, syphilitic dementia (GPI), paralysis, hysteria,
      neuralgia, epilepsy, mania, sciatica, meningitis and ataxia. Stroke was uncommon
      while Parkinson's disease and Alzheimer's disease were not mentioned, indicating
      that neurological diseases related to old age and neurodegeneration were not yet
      a threat to health. Similarly, headache, insomnia, anxiety and depression,
      hallmark of functional disorders of the modern society, were also not mentioned,
      suggesting that these disorders were indeed rare or did not cause sufficient
      concern for patients to seek help from doctors of Western medicine.

PMID- 16425552
TI  - Complete recanalization of right middle cerebral artery after intravenous
      thrombolytic therapy.

PMID- 16425553
TI  - Anatomic study of laser-assisted endoscopic cricopharyngeus myotomy.
AB  - OBJECTIVES: Laser-assisted endoscopic cricopharyngeus muscle (CPM) myotomy has
      been used to correct dysphagia caused by CPM dysfunction. The aim of this study
      was to anatomically characterize this procedure in hopes of demonstrating its
      safety and efficacy. METHODS: A Dohlman endoscope was used to isolate the CPM in
      5 lightly preserved, thawed cadavers. A carbon dioxide laser at 10 W continuous
      power was used to section through the CPM in conjunction with a micromanipulator
      connected to an operating microscope. The specimens were then carefully dissected
      and photographed to demonstrate the anatomy of the pharyngoesophageal segment,
      including the location of the incision and the condition of the tissue planes.
      The CPM was harvested for histologic studies, sectioned, and prepared with
      modified Gomori trichrome stain. RESULTS: Gross examination of the
      retropharyngeal region revealed the presence of intact buccopharyngeal fascia
      between the lasered region and the retropharyngeal space. Histologic analysis
      demonstrated sectioning of the CPM with preservation of this fascia layer.
      Placement of the endoscope was difficult in 1 cadaver, in which we were unable to
      properly identify the CPM. CONCLUSIONS: The carbon dioxide laser-assisted
      endoscopic CPM myotomy is a potentially anatomically safe and viable procedure
      when properly performed. However, the potential for violation of the
      retropharyngeal space is real.

PMID- 16425554
TI  - Predicting outcome in aged and severely ill patients with prolonged respiratory
      failure.
AB  - OBJECTIVES: Consultations for tracheotomy are often sought on aged and severely
      ill patients with respiratory insufficiency. This patient population has high
      short-term mortality rates and is difficult to stratify on the basis of expected
      outcome. We examined whether APACHE III (Acute Physiology and Chronic Health
      Evaluation III) scores or neurologic status assessment (NSA) scores in sedated
      individuals are predictive of outcome. METHODS: We performed a retrospective
      study examining aged patients who underwent tracheotomy for respiratory
      insufficiency and prolonged intubation. The APACHE III scores (n = 30) and NSA
      (based on a modified Glasgow Coma Scale) scores (n = 37) were calculated before
      tracheotomy. All patients were mildly sedated. Using APACHE III and NSA scores as
      predictor variables and using death and ability to be weaned from the ventilator
      as outcome variables, we performed a Kaplan-Meier survival analysis and a Cox
      proportional hazard regression. RESULTS: The APACHE III was not significantly
      predictive of either outcome. Higher NSA scores were associated with increased
      survival rates (log rank = 19.7, p < .0001) and longer median survival (88 days
      versus 16 days for lower scorers). Higher NSA scores also predicted a higher rate
      of ventilator independence. CONCLUSIONS: Neurologic function in sedated patients
      (and not APACHE III scores) can be used to stratify aged individuals with
      respiratory insufficiency on the basis of expected outcome.

PMID- 16425555
TI  - Destiny of autologous bone marrow-derived stromal cells implanted in the vocal
      fold.
AB  - OBJECTIVES: The aim of this study was to investigate the destiny of implanted
      autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem
      cells. We previously reported the successful regeneration of an injured vocal
      fold through implantation of BSCs in a canine model. However, the fate of the
      implanted BSCs was not examined. In this study, implanted BSCs were traced in
      order to determine the type of tissues resulting at the injected site of the
      vocal fold. METHODS: After harvest of bone marrow from the femurs of green
      fluorescent transgenic mice, adherent cells were cultured and selectively
      amplified. By means of a fluorescence-activated cell sorter, it was confirmed
      that some cells were strongly positive for mesenchymal stem cell markers,
      including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the
      injured vocal fold of a nude rat. Immunohistologic examination of the resected
      vocal folds was performed 8 weeks after treatment. RESULTS: The implanted cells
      were alive in the host tissues and showed positive expression for keratin and
      desmin, markers for epithelial tissue and muscle, respectively. The implanted
      BSCs differentiated into more than one tissue type in vivo. CONCLUSIONS: Cell
      based tissue engineering using BSCs may improve the quality of the healing
      process in vocal fold injuries.

PMID- 16425556
TI  - Laryngeal epithelial defenses against laryngopharyngeal reflux: investigations of
      E-cadherin, carbonic anhydrase isoenzyme III, and pepsin.
AB  - OBJECTIVES: This is the third annual report of an international research network
      studying the cellular impact of laryngopharyngeal reflux (LPR) on laryngeal
      epithelium. The objective of this study was to investigate the presence of E
      cadherin (epithelial cadherin; the intercellular junctional complex protein) in
      relation to the presence of (intracellular) pepsin and carbonic anhydrase
      isoenzyme III (CAIII). METHODS: Fifty-four laryngeal biopsy specimens from 18 LPR
      patients were studied by immunohistochemistry and Western blotting for pepsin, E
      cadherin, and CAIII. These data were compared to those from normal control
      subjects analyzed in another research study. RESULTS: Intracellular pepsin was
      detected in LPR patients, but not in controls. E-cadherin expression was reduced
      in patients with LPR. Carbonic anhydrase III expression was not found in the
      vocal fold or in the majority of samples taken from the ventricle of LPR patients
      and was inversely associated with E-cadherin membranous expression. CONCLUSIONS:
      The findings of depleted E-cadherin and CAIII and the presence of pepsin appear
      to correlate with LPR. The reduced protective response indicated by the reduced
      expression of CAIII may play an important role in the disruption of the
      intercellular barrier associated with the down-regulation of E-cadherin.

PMID- 16425559
TI  - Three-dimensional reconstruction of the human semicircular canals and measurement
      of each membranous canal plane defined by Reid's stereotactic coordinates.
AB  - OBJECTIVES: Equations for estimating the planar relationships of the human
      semicircular canals were devised by Blanks et al from a dissected bony labyrinth
      in a human skull. However, a similar study on the membranous semicircular canal
      planes has never been published. METHODS: In this study, the angle between each
      membranous canal plane and Reid's stereotactic horizontal plane was measured on
      serial histologic sections of 7 temporal bones from Japanese adults. We
      reconstructed the 3 semicircular canals by computer-aided 3-dimensional analysis.
      The angles between each pair of both bony and membranous canal planes were
      measured. RESULTS: In the bony labyrinth, the angles between the 2 canal planes
      of the lateral-anterior, anterior-posterior, and lateral-posterior pairs were
      90.51 degrees +/- 2.98 degrees (mean +/- SD), 91.70 degrees +/- 1.85 degrees, and
      94.52 degrees +/- 3.32 degrees, respectively. The angles between the 2 membranous
      canal planes of the lateral-anterior, anterior-posterior, and lateral-posterior
      pairs were 90.05 degrees +/- 4.74 degrees, 91.03 degrees +/- 2.93 degrees, and
      91.92 degrees +/- 5.22 degrees, respectively. CONCLUSIONS: The data from our
      study of the membranous labyrinth showed that the angles between each canal plane
      and the others were much closer to 90 degrees than was found by Blanks et al for
      the bony labyrinth.

PMID- 16425558
TI  - Comparative study of the daily lifestyle of patients with Meniere's disease and
      controls.
AB  - OBJECTIVES: This study was performed to investigate the possibility that daily
      lifestyle may have a causal relationship with Meniere's disease. METHODS: We
      conducted a questionnaire study of daily lifestyles among groups of patients with
      Meniere's disease and those with low-frequency hearing loss, and compared the
      results with those of control groups of local residents matched individually by
      gender and age. RESULTS: The Meniere's disease group diverged most widely from
      the control groups in their behavior patterns. Significant divergence was
      especially indicated in their engrossed, self-inhibiting, and time-constrained
      behaviors. Although the low-frequency hearing loss group also exhibited similar
      tendencies toward engrossment and in their feeling pressed for time, their self
      inhibiting behavior was less pronounced. There was no major difference between
      the endolymphatic hydrops patient groups and the control groups on other items in
      the study such as daily lifestyle, environmental stress, and means of relaxation.
      CONCLUSIONS: The results of the present study strongly suggest that there may be
      a link between an individual's specific behavior patterns and the onset of
      Meniere's disease.

PMID- 16425560
TI  - Radiation-induced petrous internal carotid artery aneurysm.
AB  - Iatrogenic internal carotid artery aneurysm is a rare complication of
      irradiation. There are few reported cases in the literature. A case of radiation
      induced petrous internal carotid artery aneurysm in a patient with nasopharyngeal
      cancer treated with radiotherapy is reported. The approach to managing such an
      aneurysm is discussed.

PMID- 16425557
TI  - Medial arytenoidectomy versus transverse cordotomy as a treatment for bilateral
      vocal fold paralysis.
AB  - OBJECTIVES: Transverse cordotomy (TC) and medial arytenoidectomy (MA) are
      procedures performed to enlarge the glottic airway in patients with bilateral
      vocal fold paralysis (BVFP). Both are less destructive than total arytenoidectomy
      and have distinct theoretical advantages for voice preservation, but they have
      never been compared. METHODS: The records of patients with BVFP treated with TC
      or MA were reviewed; information regarding the outcome measures of tracheotomy
      decannulation, dysphagia, Voice Handicap Index score, voice intensity, clinical
      course, and preoperative and postoperative voice quality was obtained. RESULTS:
      Seventeen patients were available for evaluation (11 with TC, 6 with MA). All 6
      patients with a preoperative tracheotomy were decannulated. Four patients in the
      MA group and 2 in the TC group had an increase in their postoperative Voice
      Handicap Index score. Two of the patients in the MA group had a decrease in
      phonatory sound pressure level of 3 dB, and 1 in the TC group had a decrease of 2
      dB sound pressure level. Patient self-report of airway status following TC or MA
      showed that 62.5% (10 of 16) were significantly better and 25% (4 of 16) were
      somewhat better. Blinded audio perceptual analysis comparing preoperative and
      postoperative voice quality showed no difference between the MA and TC groups. A
      swallowing quality-of-life instrument confirmed a lack of swallowing difficulties
      postoperatively. CONCLUSIONS: Both TC and MA are good treatment options for BVFP,
      with a low incidence of complications in postoperative voice or of swallowing
      difficulties and a consistent improvement of laryngeal airway restriction
      symptoms.

PMID- 16425561
TI  - Efficacy of montelukast in the treatment of nasal polyposis.
AB  - OBJECTIVES: Twenty-four consecutive patients with symptomatic nasal polyposis and
      nonallergic or perennial rhinitis who were undergoing chronic nasal steroid
      therapy were prospectively evaluated for response to adjunctive oral montelukast
      sodium therapy. METHODS: The patients were undergoing daily intranasal steroid
      sprays for a minimum of 6 months before being started on montelukast sodium 10 mg
      by mouth per day for 3 months while intranasal steroids were continued. The
      patients were given a validated symptom score survey at the start and end of
      therapy, with a lower score indicating fewer symptoms. The nasal polyps were
      submitted to biopsy before and after treatment to determine their degree of
      eosinophilia. Eosinophilia was graded in a blinded fashion by an independent
      pathologist on a scale of 0 to 3, with 3 being severe. Patients with seasonal
      allergies were excluded, and the studied patients were treated during the winter
      season to avoid confounding by potential seasonal allergic responses. RESULTS:
      The patients tended to improve on montelukast therapy in terms of their symptom
      scores and polyp eosinophil counts. The symptoms improved in 17 patients (71%)
      and remained the same or worsened in 7 patients (29%). The symptom score for the
      group improved from a pretreatment value of 33.4 (SD, 7.73) to a posttreatment
      value of 23.3 (SD, 13.73; p < .001). In addition, the eosinophilia score improved
      from 2.3 (SD, 0.68) to 1.5 (SD, 0.82; p < .01). The improvement was most
      noticeable in the patients with perennial allergies. CONCLUSIONS: These results
      suggest that montelukast appears to be beneficial for some patients with nasal
      polyposis. Patients with perennial allergies and nasal polyposis seem more likely
      to respond to the treatment than those with nonallergic nasal polyposis.

PMID- 16425562
TI  - Conservative management of stapler failure in Zenker's endoscopic
      diverticulotomy.
AB  - The endoscopic stapler has achieved widespread use in the management of Zenker's
      diverticulum owing to its ease of use and safety. However, complications
      associated with its use can and do occur. This study details the treatment course
      of 2 patients who underwent an endoscopic stapler approach to their Zenker's
      diverticulum complicated by the stapler's not sealing the mucosal edges. Although
      the patients' hospital stays were extended as a result, they suffered no long
      term morbidity as a result of the complication.

PMID- 16425563
TI  - Acoustic rhinometry: accuracy and ability to detect changes in passage area at
      different locations in the nasal cavity.
AB  - OBJECTIVES: To evaluate the accuracy of acoustic rhinometry (AR) measurements,
      and to assess how well AR detects obstructions of various sizes at specific sites
      in the nasal cavity, we created a cast model from an adult cadaver nasal cavity.
      METHODS: The actual cross-sectional areas of the cast model nasal passage were
      determined by computed tomography and compared with the corresponding areas
      measured by AR. To assess how nasal obstruction affects the AR results, we placed
      small wax spheres of different diameters at specific sites in the model (nasal
      valve, head of the inferior turbinate, head of the middle turbinate, middle of
      the middle turbinate, choana, and nasopharynx). RESULTS: The AR-derived cross
      sectional areas in the first 6.5 cm of the cast model nasal cavity were very
      close to the corresponding areas calculated from computed tomographic sections
      perpendicular to the presumed acoustic axis. However, AR overestimated the
      passage areas at locations posterior to the 6.5-cm point. Acoustic rhinometry
      gave an accurate indication of the passage area of the nasal valve and its
      distance from the nostril. The nasal valve and the choana were indicated by
      significant dips on the AR area-distance curve, whereas the curve was smooth
      throughout the region that included the head of the inferior turbinate, the head
      of the middle turbinate, the middle of the middle turbinate, and the nasopharynx.
      In other words, AR did not discretely identify these latter sites. Acoustic
      rhinometry detected the different-sized inserts (obstructions) more accurately at
      the nasal valve than at sites posterior to this location. CONCLUSIONS: The
      results of the study show that AR is a valuable method for assessing the anterior
      nasal cavity. This technique is sensitive for detecting changes in passage area
      at the nasal valve region; however, the sensitivity is lower at sites posterior
      to this. The findings suggest that when there is substantial narrowing of the
      nasal valve, AR will not identify an obstruction at any location posterior to the
      nasal valve. In such situations, AR measurements beyond the abnormal nasal valve
      may easily lead to misinterpretation of the patient's nasal anatomy or condition.

PMID- 16425565
TI  - Tuberculous parotitis.

PMID- 16425566
TI  - Labouring women and birth technology: the midwife as conduit?

PMID- 16425564
TI  - Immunohistochemical analyses of MUC5AC mucin expression in sinus mucosa of
      children with sinusitis and controls.
AB  - OBJECTIVES: The purpose of this study was to analyze MUC5AC protein expression in
      sinus mucosal specimens of children with and without chronic sinusitis. METHODS:
      Morphometric, histologic, and immunohistochemical analyses were carried out on
      sinus mucosa of 7 children with chronic sinusitis and 6 children without
      sinusitis. RESULTS: MUC5AC protein was expressed in a subset of goblet cells in
      the surface epithelium, but not in the submucosal glands in either pediatric
      population. The number of goblet cells that expressed MUC5AC mucin was not
      significantly different in patients with and without chronic sinusitis. All
      specimens had similar numbers of goblet cells in the surface epithelium.
      CONCLUSIONS: The data demonstrate that neither goblet cell hyperplasia nor
      increased MUC5AC expression occurs in the sinus mucosa of children with chronic
      sinusitis. This suggests that in contrast to asthma, in which goblet cell
      hyperplasia is present in the lower respiratory tract, mucus hypersecretion in
      pediatric chronic sinusitis may involve other secretory cells, eg, submucosal
      glandular cells, and mucins secreted by these glandular cells.

PMID- 16425567
TI  - Birth technology device: an appraisal.

PMID- 16425568
TI  - Who wants to be a consultant midwife?

PMID- 16425569
TI  - Recruitment levels in the north-west during this time.

PMID- 16425570
TI  - Controversy surrounding management of third stage of labour.

PMID- 16425571
TI  - Technology needs to be harnessed and used appropriately in childbirth. Do you
      agree?

PMID- 16425572
TI  - The effect of TNFalpha blockade on the antinuclear antibody profile in patients
      with chronic arthritis: biological and clinical implications.
AB  - Since the first proof of efficacy of TNFalpha blockade, both the number of
      patients treated worldwide and the number of indications for treatment with
      TNFalpha blockers have grown steadily. Surprisingly, the profound
      immunomodulation induced by anti-TNFalpha therapy is associated with a relatively
      low incidence of immune-related complications such as lupus-like syndromes and
      demyelinating disease. This contrasts sharply with the prominent induction of
      autoantibodies such as antinuclear antibodies (ANA) and anti-dsDNA antibodies
      during TNFalpha blockade. Although this phenomenon has been recognized for
      several years, the clinical and biological implications are not yet fully
      understood. In this review, recent studies analysing the effect of TNFalpha
      blockade (infliximab and etanercept) on the ANA profile in autoimmune arthritis
      will be discussed. Taken together, these reports indicate that the prominent ANA
      and anti-dsDNA autoantibody response is 1) not a pure class effect of TNFalpha
      blockers, 2) independent of the disease background, 3) largely restricted to the
      induction of short-term IgM anti-dsDNA antibodies, and 4) not associated with
      other serological or clinically relevant signs of lupus. Nevertheless, a careful
      follow-up of patients treated with TNFalpha blockers remains mandatory, including
      monitoring for lupus-like characteristics.

PMID- 16425573
TI  - Male systemic lupus erythematosus in a Latin-American inception cohort of 1214
      patients.
AB  - The objective of the study was to evaluate the influence of the male gender in
      the clinical presentation and outcome of systemic lupus erythematosus in a
      prospective inception cohort of Latin-American patients. Of the 1214 SLE patients
      included in the GLADEL cohort, 123 were male. Demographic characteristics as well
      as clinical manifestations, laboratory profile, activity and damage scores were
      evaluated at onset and during the course of the disease and compared with female
      patients. The median age at onset of the male patients was 27 and that at
      diagnosis 29.2 years. Delay to diagnosis was shorter in males (134 versus 185
      days, P = 0.01). At onset, men more frequently showed fever (42.3 versus 27.0%, P
      = 0.001) and weight loss (23.6 versus 11.8%, P = 0.001). During disease course
      the incident of symptoms was: fever, 67.8 versus 55.6%, P = 0.012; weight loss,
      47.2 versus 24.3%, P = 0.001; arterial hypertension, 37.4 versus 25.8%, P =
      0.007; renal disease (persistent proteinuria and/or cellular casts), 58.5 versus
      44.6%, P = 0.004); and hemolytic anemia, 19.5 versus 10.9%, P = 0.008. The
      laboratory results showed that: men more frequently had IgG anticardiolipin
      antibodies (68.2 versus 49%, P = 0.02) and low C3 (61.3 versus 48.1%, P = 0.03);
      5/123 men died (4%) compared with 29/1091 women (2.7%). In conclusion, 10% of
      GLADEL's cohort patients were male. They showed a distinctive profile with
      shorter delay to diagnosis, higher incidence of fever, weight loss, arterial
      hypertension, renal disease, hemolytic anemia, IgG anticardiolipin antibodies and
      low C3. Although not statistically significant, mortality was higher in men.

PMID- 16425574
TI  - Angiotensin inhibition or blockade for the treatment of patients with quiescent
      lupus nephritis and persistent proteinuria.
AB  - Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker
      (ARB) reduces proteinuria and the rate of renal function deterioration in
      diabetic nephropathy and other glomerular diseases, but its role in quiescent
      lupus nephritis has not been established. We conducted a retrospective study to
      investigate the effects of ACEI/ARB on proteinuria and renal function in patients
      with persistent proteinuria (>1 g/day) despite resolution of acute lupus
      nephritis following immunosuppressive treatment. Fourteen out of 92 patients were
      included. The duration of treatment with ACEI/ARB was 52.1 +/- 35.7 months. The
      levels of proteinuria, serum albumin, serum creatinine, systolic and diastolic
      blood pressure were 1.10 to 6.90 g/day, 35.8 +/- 3.6 g/L, 102.54 +/- 34.48
      micromol/L, 137.6 +/- 10.9 and 81.9 +/- 9.2 mmHg at baseline. Proteinuria and
      serum albumin showed significant sustained improvements after 6 and 24 months of
      treatment. Comparison of slopes for serial proteinuria, albumin and reciprocal of
      serum creatinine before and after treatment showed significant improvements in
      six (43%), eight (57%) and two patients, respectively. At last follow-up
      proteinuria remained significantly lower (0.36 g/day, P = 0.043) and albumin
      higher (41.3 +/- 2.2 g/L, P = 0.023). Eleven (78.6%) patients had proteinuria
      improved by >50%, and five had insignificant proteinuria at last follow-up.
      Systolic blood pressure was significantly reduced from 6 months onwards, but this
      did not correlate with proteinuria reduction. Diastolic blood pressure, serum
      creatinine, creatinine clearance, anti-dsDNA, C3 and haemoglobin were not
      altered. We conclude that ACEI/ARB effectively reduces proteinuria and improves
      serum albumin in patients with persistent proteinuria despite quiescent lupus
      nephritis.

PMID- 16425575
TI  - Complement-fixing activity of anticardiolipin antibodies in patients with and
      without thrombosis.
AB  - We have analysed in vitro the complement-fixing activity of anticardiolipin
      antibodies (C-fix aCL) from patients with persistent and moderate/high titres IgG
      aCL antibodies: 21 with thrombosis and 11 without thrombosis. Titre and C-fix
      ability of aCL were measured by ELISA. APS and non-APS patients were similar with
      regard to mean levels of IgG aCL (46 +/- 24 versus 51 +/- 30 GPL, P = 0.7),
      frequency of IgM aCL (P = 0.7) and a comparable predominance of IgG2 aCL
      reactivity on ELISA (95% versus 100%, respectively, P = 1.0). Remarkably, a high
      frequency of C-fix aCL (71% versus 92%, P = 0.35) was observed in both groups.
      Similarly, no difference was observed in the mean level of C-fix aCL in APS and
      non-APS patients (7 +/- 6 versus 9 +/- 8 SDunits, P = 0.3). Analysis of 10
      primary and 11 secondary APS also revealed a comparable IgG aCL mean titre (57 +/
      29 versus 37 +/- 11, P = 0.06), frequency of IgM aCL (P = 0.6) and of C-fix aCL
      (70% versus 73%, P = 0.99). Among APS patients six had exclusive arterial events
      and seven exclusive venous events. The IgG aCL mean titre (36 +/- 10 versus 36 +/
      11 GPL, P = 0.9) and the frequency of IgM aCL antibodies (P = 0.56) in these
      subgroups of patients were comparable. There was a trend of higher frequency of C
      fix aCL in patients with exclusive venous events (100%) compared to 50% of those
      with exclusive arterial events (p = 0.07). Importantly, C-fix aCL titre was
      higher in the former group compared to the later one (8 +/- 5 SDunits versus 2 +/
      2 SDunits, P = 0.016). Our data support the notion of a high frequency of C-fix
      aCL in APS. Although it does not discriminate those patients without thrombotic
      events with persistent moderate/high levels of aCL, this property seems to be
      more relevant in venous events and may provide the basis for further
      understanding the distinct pathogenic mechanisms underlying arterial and venous
      occlusive disorders of APS.

PMID- 16425576
TI  - The shrinking lung syndrome in systemic lupus erythematosus: improvement with
      corticosteroid therapy.
AB  - Respiratory manifestations of systemic lupus erythematosus (SLE) are frequent.
      The 'shrinking lung syndrome' (SLS) represents a rare complication of SLE. The
      pathogenesis and therapy of the SLS remains controversial. We report a series of
      five consecutive cases with the SLS of which we provide a detailed description of
      the extent and dynamics of the response to corticosteroid therapy.

PMID- 16425577
TI  - JC virus meningitis in a patient with systemic lupus erythematosus.
AB  - The human neurotropic JC virus (JCV) is most commonly acquired during childhood,
      and, because no clinical illness has been associated with primary infection, is
      presumed to be asymptomatic. In the immunocompromised host, JCV is responsible
      for progressive multifocal leukoencephalopathy (PML). We describe a patient with
      longstanding systemic lupus erythematosus who presented with acute meningitis
      without encephalitis or PML. JCV was the only pathogen found in the cerebrospinal
      fluid suggesting a primary infection or symptomatic reactivation. Our observation
      demonstrates the expanding clinical importance of JCV in autoimmune diseases, and
      diagnostic tests for JCV should be included in the investigative work-up for
      meningitis or encephalitis in these patients.

PMID- 16425578
TI  - Catastrophic antiphospholipid syndrome and Kikuchi-Fujimoto disease: the first
      case reported.
AB  - The case of a man with diagnosis of Kikuchi-Fujimoto disease (KFD) and
      catastrophic antiphospholipid syndrome (CAPS) is reported. He presented prolonged
      fever, lymphadenopathies, arthralgia, weight loss, hepatosplenomegaly and
      positive IgM for cytomegalovirus. While he was empirically treated with
      tuberculostatic drugs, he suddenly developed systemic inflammatory response
      syndrome, multiple organ failure and distal necrosis. On suspicion of severe
      sepsis, antibiotics, corticoids and recombinant human activated protein C
      (XIGRIS) were administrated. Exhaustive laboratory searching was negative.
      Histopathologic examinations of lymph node first disclosed malignant lymphoma but
      later KFD was confirmed. One month later, laboratory tests showed the presence of
      antiphospholipid antibodies (aPL). The patient was discharged after two months of
      hospitalization. This case exhibits a KFD complicated by definite CAPS.
      Cytomegalovirus could be involved in the development of both CAPS and KFD.
      Because of the severity of the case, we believe that XIGRIS noticeable improved
      the altered coagulation profile associated with CAPS.

PMID- 16425579
TI  - Lupus in Baltimore: evidence-based 'clinical pearls' from the Hopkins Lupus
      Cohort.
AB  - The Hopkins Lupus Cohort is a prospective longitudinal study of lupus activity,
      organ damage, and quality of life in SLE patients. It is balanced between
      Caucasian and African-American SLE patients. This review highlights major
      findings from the cohort with implications for clinical care.

PMID- 16425580
TI  - Sweet syndrome as an initial presentation in a child with systemic lupus
      erythematosus.

PMID- 16425581
TI  - Slow development of massive splenomegaly, portal and pulmonary hypertension in
      systematic lupus erythematosus: can nodular regenerative hyperplasia of the liver
      explain all these findings?

PMID- 16425582
TI  - Acute and fulminant Budd-Chiari syndrome in a well-anticoagulated patient with
      primary antiphospholipid syndrome.

PMID- 16425583
TI  - Assessing the psychosocial work environment--"subjective" versus "objective"
      measurement.

PMID- 16425584
TI  - Reproducibility and validity of workers' self-reports of physical work demands.
AB  - The objective of this paper is to provide a systematic review of the
      reproducibility and validity of self-report questions concerning physical work
      demands. After a bibliographic search of Medline and Ergonomic Abstracts for 1980
      2003, 15 articles meeting the eligibility criteria were reviewed for
      methodological quality; 82 formulations of questions on physical work demands
      were evaluated for reproducibility and 83 for validity. Questions evaluated for
      both reproducibility and validity that performed well in both sets of studies
      included those on duration or presence of sitting and standing posture, the
      presence of walking, kneeling or squatting postures, duration or frequency of
      hands above shoulders, manual handling of more than or less than 10 kg, general
      level of physical effort, presence and duration of whole-body vibration, and
      duration of the use of visual display terminals. Suggestions for improving the
      design of reproducibility and validity studies and directions for future research
      in physical workload measurement are proposed.

PMID- 16425585
TI  - The Copenhagen Psychosocial Questionnaire--a tool for the assessment and
      improvement of the psychosocial work environment.
AB  - OBJECTIVES: The aim of this article is to present the Copenhagen Psychosocial
      Questionnaire (COPSOQ), a questionnaire developed in three different lengths for
      assessing psychosocial factors at work, stress, and the well-being of employees
      and some personality factors. The purpose of the COPSOQ concept is to improve and
      facilitate research, as well as practical interventions at workplaces. METHODS:
      The development of the questionnaire was based on a survey of a representative
      sample of 1858 Danish employees aged 20-59 years. The response rate was 62%; 49%
      were women. Altogether 145 questions from some international and Danish
      questionnaires and 20 self-developed questions were tested with factor analyses,
      analyses of internal reliability, and analyses of response patterns. RESULTS: The
      analyses resulted in a long research version of the questionnaire with 141
      questions and 30 dimensions, a medium-length version for work environment
      professionals with 95 questions and 26 dimensions, and a short version for
      workplaces with 44 questions and 8 dimensions. Most of the scales have good
      reliability, and there seems to be very little overlap between the scales. A
      novel feature of the COPSOQ is the development of five different scales on
      demands at work. CONCLUSIONS: The COPSOQ concept is a valid and reliable tool for
      workplace surveys, analytic research, interventions, and international
      comparisons. The questionnaire seems to be comprehensive and to include most of
      the relevant dimensions according to several important theories on psychosocial
      factors at work. The three versions facilitate communication between researchers,
      work environment professionals, and workplaces.

PMID- 16425586
TI  - Meta-analysis of silicosis and lung cancer.
AB  - OBJECTIVES: This study examined the association between silicosis and lung cancer
      in a systematic review (and meta-analysis) of the epidemiologic literature, with
      special reference to the methodological quality of observational studies.
      METHODS: We searched Medline, Toxline, BIOSIS and Embase (1966-May 2004) for
      original articles published in any language and systematically reviewed the
      bibliographies of the retrieved articles. Observational studies (cohort and case
      control studies) were selected if they reported a measure of association
      [standardized mortality ratio (SMR), relative risk or odds ratio] relating lung
      cancer to silicosis. RESULTS: Thirty-one studies (27 cohort studies, 4 case
      control studies) met the inclusion criteria of the meta-analysis. Without any
      adjustment for smoking, the meta-analysis of the cohort studies indicated that
      the common SMR was 2.45 [95% confidence interval (95% CI) 1.63-3.66; homogeneity
      P<0.0001]. When the results of the cohorts for which mortality data were adjusted
      for smoking were pooled, the common SMR was 1.60 (95% CI 1.33-1.93; homogeneity
      P=0.52). In a "dose-response" analysis, the profusion of small and large
      opacities found in chest X-rays correlated with the risk of death from lung
      cancer. Overall, the case-control studies were more conservative in their
      conclusions. CONCLUSIONS: Because of biases inherent to observational studies, it
      is likely that the risk of lung cancer among silicosis patients is overestimated
      in the current literature. There is nevertheless evidence, from data restricted
      to never-smokers and from a "dose-response" analysis, that silicosis and lung
      cancer are associated.

PMID- 16425587
TI  - Pleuropulmonary lesions, ergotamines and asbestos exposure.
AB  - OBJECTIVES: This study investigated the possibility of pleuropulmonary lesions,
      which can occur as rare but serious side effects of different ergot drugs,
      occurring more commonly in persons earlier exposed to asbestos. METHODS: All
      reports of pleuropulmonary side effects of the ergot drugs used in Sweden in the
      Swedish side effect registry from 1985 to 2003 were studied. In addition, the
      literature was reviewed. RESULTS: In the registry, 47 men and 3 women were found.
      Of the men, 24 were exposed to asbestos, and 2 denied such exposure; 2 of the 3
      women were exposed. In the literature, 111 patients were found--32 had confirmed
      exposure and 15 denied it. For most of the patients, it was not possible to
      determine exposure. CONCLUSIONS: Enough evidence exists to postulate that earlier
      asbestos exposure in combination with the intake of ergot drugs can cause
      pleuropulmonary lesions.

PMID- 16425588
TI  - Passive smoking exposure among adults and the dynamics of respiratory symptoms in
      a prospective multicenter cohort study.
AB  - OBJECTIVES: The aim of this study was to measure the effects of past exposure to
      environmental tobacco smoke on the day-to-day dynamics of four respiratory
      symptom classes in a diary study including adult never-smokers. METHODS: As part
      of SAPALDIA (Swiss study on air pollution and lung diseases in adults), a
      prospective multicenter cohort study, 1421 life-time adult nonsmokers were
      followed for 2 years with the use of daily questionnaires filled out during one
      to six periods of 4 weeks spread over 2 years (1992-1993). The hazard ratios (HR)
      of getting or losing respiratory symptoms from one day to another were determined
      in association with past exposure to environmental tobacco smoke. RESULTS: In a
      sample of adult never-smokers, an association between self-reported past exposure
      to environmental tobacco smoke and deteriorated average symptom dynamics was
      found for all of the outcomes considered, showing HR values from 1.09 to 1.21 for
      developing symptoms and HR values from 0.91 to 0.83 for getting rid of them.
      Exposure to environmental tobacco smoke, including the workplace, was negatively
      associated with the length of intervals without symptoms of bronchitis (HR 1.33)
      and asthma (HR 1.27), while exposure to environmental tobacco smoke confined to
      places outside work was positively associated with the length of episodes of any
      respiratory symptom and lower-respiratory-tract symptoms (HR 0.78-0.77).
      CONCLUSIONS: The results suggest that exposure to environmental tobacco smoke has
      adverse effects on the dynamics of respiratory symptoms, and the size (magnitude)
      and type of effects appear to depend on the place of exposure.

PMID- 16425589
TI  - Influence of childhood atopic dermatitis on future worklife.
AB  - OBJECTIVES: The purpose of this study was to perform a population-based follow-up
      of people with childhood atopic dermatitis with respect to the possible influence
      on their worklife. METHODS: Medical records of the school health care services in
      Stockholm, Sweden, were reviewed for people born between 1960 and 1969.
      Altogether 600 persons with signs of atopic dermatitis ("cases") and 600 matched
      controls without eczema ("controls") were identified. Of these people, 405 cases
      and 378 controls answered a postal questionnaire focusing on choice of job,
      occupational exposure, past and present skin disease, and change of job due to
      eczema. RESULTS: The proportions of cases and controls in jobs with a high risk
      of hand eczema were similar, as was the exposure to water, detergents, chemicals,
      and hand washing. The self-reported cumulative prevalence of hand eczema was 42%
      for the cases and 13% for the controls (P<0.001). The 1-year prevalence was 24%
      for the cases and 9% for the controls (P<0.001). Among the cases, 9% reported a
      change of job due to eczema compared with 2% of the controls (P<0.001). The
      corresponding proportions of sick leave were 10% and 2% (P<0.001). CONCLUSIONS:
      In conclusion, a history of atopic dermatitis in childhood does not seem to
      influence the choice of job nor hazardous occupational skin exposure. It does,
      however, mean an increased risk for job changes, sick leave, and medical
      consultations, mainly due to the increased risk of hand eczema.

PMID- 16425590
TI  - Vote for self-regulation.

PMID- 16425591
TI  - Suffer the children.
AB  - The nation was shocked by the death of eight-year-old Victoria Climbie who was
      murdered by her great aunt and her boyfriend in February 2000. Starved, beaten
      and forced to sleep in a bath while bound hand and foot, and tied up in a bin
      bag, the Climbie Inquiry found Victoria had been let down by a 'gross failure of
      the system' that should have protected her.

PMID- 16425592
TI  - Happier endings.
AB  - A new initiative from the Department of Health aims to improve care at the end of
      life. This involves consulting patients and relatives about their needs and
      desires. End-of-life care (EOLC) works with non-specialist care staff. It
      operates in community care, acute care and nursing home settings. The programme
      builds on tools developed for the care of cancer patients. With a national
      support team, the programme is being driven through strategic health authorities
      and primary care trusts.

PMID- 16425593
TI  - The way ahead.
AB  - Nursing experts suggest that the key demands of our Charter for Change campaign
      will remain high on the nurse education agenda in the future.

PMID- 16425594
TI  - Dinner table conversation.

PMID- 16425595
TI  - Who's looking after the carers?

PMID- 16425596
TI  - Go whistle for it.

PMID- 16425597
TI  - Our level best.

PMID- 16425599
TI  - Learning and sharing safety lessons to improve patient care.
AB  - Nurses are at the forefront of patient safety and are constantly reviewing their
      practice to improve care delivery. When things go wrong in health care the
      consequences can be distressing for patients and staff. Lessons need to be
      learned and acted on to minimise the likelihood of reoccurrence. The 'root cause
      analysis' approach provides nurses and other healthcare staff with a consistent
      and structured methodology to investigate incidents. It enables staff to identify
      where systems are failing and where improvements in patient care and safety can
      be made.

PMID- 16425598
TI  - Promoting privacy and dignity for older patients in hospital.
AB  - This article defines dignity and suggests some practical guidance on ways that
      dignity can be a priority in daily clinical practice, drawing on work undertaken
      at Addenbrooke's Hospital (Cambridge University Hospitals NHS Foundation Trust).
      It then focuses on the dignity of older patients receiving palliative care in
      hospital. The discussion includes hypothetical scenarios which the authors hope
      will resonate with the reader and help to stimulate change within clinical areas.

PMID- 16425600
TI  - Caring for the mechanically ventilated patient: part two.
AB  - This is tile second of two articles on caring for the mechanically ventilated
      patient. It focuses on the process of weaning patients from mechanical
      ventilators The first part, on caring for tile mechanically ventilated patient,
      was published in last week's Nursing Standard.

PMID- 16425601
TI  - Sickle cell disorders.

PMID- 16425602
TI  - Pension parity.

PMID- 16425604
TI  - There's no need to stop.

PMID- 16425603
TI  - Emergency route.

PMID- 16425605
TI  - Mentoring learners in practice: No. 17. Helping learners to plan care.

PMID- 16425606
TI  - Just what the doctor ordered...not really.

PMID- 16425607
TI  - Physician documentation in support of appropriate billing with modifier '-25'.
AB  - What is one of the surest ways for a practice to lose revenue and invite the
      unwanted attention of government auditors? By failing to select and document the
      appropriate use of modifiers to code for services provided. For example, the
      Office of Inspector General (OIG) has made it known that they will closely review
      professional billing with the use of modifier '-25.' The use of this particular
      modifier appeared on their radar screen, because in one recent year Medicare paid
      approximately 1.7 billion dollars for Evaluation and Management (E/M) services
      billed with modifier '-25'. The OIG feels an increase of this amount warrants
      further investigation to determine if these claims were billed and reimbursed
      appropriately. Additionally, Oklahoma Medicaid auditors are actively scrutinizing
      the use of modifier '-25' to a degree even more stringent than Medicare and the
      CPT code book's description allow. Therefore, it is important that physicians be
      knowledgeable in determining when it is appropriate to bill using this modifier.

PMID- 16425608
TI  - Mechanisms of head injury in bull riders with and without the Bull Tough helmet-
      a case series.
AB  - INTRODUCTION: Bull riding is one of the most dangerous sporting activities of the
      modern era. Head injuries are common in bull riders, yet helmets and faceguards
      are rarely mandated in competitive bull riding events and few participants use
      such protective headgear. OBJECTIVE: The purpose of examining this case series
      was to characterize head and face injuries in bull riders, to gain a better
      understanding of the mechanisms associated with the various injury types and to
      assess the effect of wearing the Bull Tough Helmet (BTH). METHODS: A survey was
      sent to 320 bull riders, asking them to provide details about the head and face
      injuries they had sustained while bull riding with and without the BTH. Eighty
      one (31%) of the 265 surveys that reached their intended athlete were completed
      and returned. Riders were also asked to describe specific incidents where the BTH
      had saved them from head injury. RESULTS: Respondents described 84 incidents of
      injury while not wearing the BTH; 110 injuries resulted. Respondents described 33
      incidents of injury while wearing the BTH; 39 injuries resulted. Specific
      mechanisms and injury types were reported for both cohorts with concussions,
      lacerations and facial fractures being the most common injury types. In addition,
      respondents described 170 events in which an injury was prevented by the BTH.
      CONCLUSIONS: Bull riders are at great risk of suffering severe head and facial
      injuries. Safe and effective helmets with protective face guards must be worn by
      bull riders if the incidence of these injuries is to be diminished.
      Organizations, promoters and schools that sponsor bull riding events, especially
      for minors, should mandate protective headgear in order to better protect these
      athletes.

PMID- 16425609
TI  - Vestibulotoxicity: a risk of home aminoglycoside therapy.
AB  - Home intravenous therapy is a cost-effective method of providing prolonged
      antibiotic therapy. Home infusion of aminoglycosides, however, may produce
      irreversible vestibular damage. Unfortunately, neither serum levels nor daily
      dosing precludes vestibulotoxicity. Four patients who developed disabling
      vestibulotoxicity while being treated at home with aminoglycosides are presented.
      Details of the original illness, antibiotic therapy, vestibular symptoms, and
      their outcomes are presented. All patients presented with sudden onset of severe
      disequilibrium and bilateral vestibular loss confirmed by electronystagmography.
      None of these patients experienced hearing loss or vertigo. Initial serum levels
      were normal in three cases. Common misconceptions about aminoglycoside
      ototoxicity and the inherent risks of home aminoglycoside therapy are discussed.
      Vestibulotoxicity is difficult to diagnose and there is no safe dose or
      monitoring schedule. Therefore, aminoglycosides should be avoided if possible.
      Physicians using aminoglycosides should be aware of the risks involved and
      patients informed appropriately.

PMID- 16425610
TI  - OSMA and Oklahoma medicine: 1976-1985.

PMID- 16425611
TI  - A matter of interpretation 2: HIPAA and Title VI rules for interpreters and
      translators.

PMID- 16425612
TI  - Patient page #66. Are you worried about lead poisoning?

PMID- 16425614
TI  - Interspecies differences of motor units properties in the medial gastrocnemius
      muscle of cat and rat.
AB  - The purpose of the study was to analyze the interspecies differences of motor
      unit contractile properties in two most frequently studied mammals: cats and
      rats. A total sample of 166 motor units (79 in cats and 85 in rats) was
      investigated in the medial gastrocnemius muscle. Considerable differences were
      found in composition of the studied muscle. In cats, fast fatigable, fast
      resistant and slow units formed 68, 18 and 14% of the investigated population,
      whereas in rats 36, 52 and 12%, respectively. The contraction and relaxation
      times of motor units in the cat muscle were evidently longer than in the rat and
      the border values for fast/slow motor units division in these species were 44 and
      20 ms, respectively. The mean values of twitch and tetanic forces appeared to be
      7-8 times lower in rats, for fast, while 2-5 times for slow motor units. Also
      variability between the strongest and the weakest units within each type revealed
      differences 10-60 times in cats, whereas only 3.5-14 times in rats. The summation
      of twitches into tetanus for fast units was comparable in both species, but for S
      units was evidently more effective in the cat. In fast motor units' tetanic
      contractions evident interspecies differences concerned sag appearance and
      profiles of unfused tetani of FF and FR units. Differences in contractile
      properties described in the study may depend on the size, number and innervation
      ratio of motor units in the muscle of cat and rat, as well as their biochemical
      variability. Differences in composition of motor unit types and uneven mechanisms
      of force development may reflect biological adaptation to variable behaviour of
      cats and rats.

PMID- 16425613
TI  - The effects of normovolemic hemodilution on protein synthesis recovery following
      postischemic reperfusion in the rat brain.
AB  - Normovolemic hemodilution is a possible way to improve the brain recovery after
      ischemia and reperfusion. Therefore we have decided to examine how this process
      may affect the post-ischemic protein synthesis machinery. We analysed rat brains
      after 4-vessel-occlusion and different time intervals of reperfusion using
      normovolemic hemodilution. We achieved an important increase of [4,5-3H]leucine
      incorporation into polypeptides in vitro in the rat brain neocortex 30 minutes
      after ischemia, but concurrently there was no significant change in the
      hippocampus and striatum. By extending the time course of reperfusion we did not
      observe any important deviation of in vitro [4,5-3H]leucine incorporation in the
      studied brain areas. Thus, although hemodilution increased protein synthesis in
      selective vulnerable regions after ischemia, this improvement is not of
      significant importance.

PMID- 16425615
TI  - Implicit and explicit memory formation: influence of gender and cultural habits.
AB  - The study was aimed to investigate whether impending surgery, considered as a
      stressful life event, might interfere with memory formation like other stress and
      anxiety conditions do. Results do not support the hypothesis. Implicit and
      explicit memory performance are both unaffected by presurgery condition and seem
      influenced, rather, by subjects gender, education and cultural habits. Females
      perform generally better than males and, regardless of age and sex, higher
      educated individuals score higher on the explicit memory task. The habits of
      reading books and doing crosswords are associated to best performance on explicit
      and implicit memory task respectively.

PMID- 16425616
TI  - Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged
      freely-moving rats.
AB  - In chronically-implanted, drug-free, behaving aged Fischer rats,
      intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) acetyl-L
      carnitine (ALCAR) injections powerfully enhanced motor behavior and head
      movements aimed at attention and exploratory activity. This effect was dose
      dependent and associated with the abolition or substantial reduction of the
      incidence and duration of the spontaneous EEG generalized hypersynchronous
      patterns termed High Voltage Spindle (HVS), with an increase in EEG monitored
      theta activity. The results suggest that ALCAR may stimulate the motivational
      system and disrupt the hypersynchronous processes by inhibiting the GABAergic
      thalamic reticular neurons and/or activating the brain stem cholinergic reticular
      system (pedunculo pontine tegmental, PPT and laterodorsal tegmental, LDT nuclei).

PMID- 16425617
TI  - Stroop effects from 3 to 10 years: the critical role of reading acquisition.
AB  - We studied 241 nursery and primary school 3- to 10-year old children with a
      discrete-trial version of the Stroop Test, including both a Color-Naming and (for
      the 6- to 10-year olds only) a Word-Reading task. The classic Stroop effect was
      present across all the ages, with an inverted U-shaped pattern: increasing from 3
      to 7-year olds, then decreasing. Preschool children who were able to read showed
      a Stroop effect larger than same-age, unable to read children. The reverse Stroop
      effect was present across all the studied ages but the 6-year-olds, who instead
      displayed some facilitation in reading congruent vs. black words. Since the
      acquisition of reading skills turned out to be crucial for the Stroop effects,
      the present research may be useful to study developmental reading impairments by
      providing normative data.

PMID- 16425619
TI  - Surgeons and disasters: new challenges, new opportunities.

PMID- 16425618
TI  - Are surgeons playing leadership roles in disaster preparedness and planning?

PMID- 16425620
TI  - The ABC's of disaster response.
AB  - The readiness of our healthcare facilities to respond to terrorist acts or
      naturally occurring epidemics and disasters has been at the center of public
      attention since September 11, 2001. The many other tragic events that have
      occurred throughout the world since then further reinforce the need for all
      healthcare facilities and medical personnel to increase their level of
      preparedness if they wish to optimize outcomes. Maximizing survival rates and
      minimizing disability during any MCI hinges on rapid, seamless, and coordinated
      response between first responders and first receivers. The Incident Command
      System and the HEICS are organizational tools that form the foundation for such a
      rapid and coordinated response. The ICS provides a simple and adaptable
      management structure that is capable of being expanded or contracted to meet the
      needs of a specific situation. The HEICS adapts the ICS into the hospital setting
      and, in addition to the benefits stated above; its use of the ICS nomenclature
      and terminology facilitates the communication and the sharing of resources
      between all agencies and health care institutions involved. A basic knowledge and
      understanding of the ICS principles and structure is essential for all
      individuals participating in a disaster response. Previous efforts at disaster
      preparedness have focused predominantly on the pre-hospital and rescue phase of
      the disaster response, but a complete and coordinated community response requires
      creation of integrated disaster plans. True readiness can only be achieved by
      testing and modifying these plans through integrated simulation drills and table
      top exercises. Hospital-wide drills are essential to educate all staff members as
      to their institutional plan and serve as the only substitute at present to first
      hand experience. At present, there is no evidence-based literature to define what
      constitutes the best medical response by medical personnel within a disaster
      setting. This information will likely evolve over the next several decades as we
      now recognize Disaster Medicine as a separate scientific and medical entity. In
      the interim, we can develop and modify our response plans based on the "lessons
      learned" from past experience. Prior events have demonstrated that general
      surgeons and surgical subspecialists are critical components to a successful
      hospital response for the vast majority of all mass casualty incidents. Thus,
      surgeons must take responsibility for increasing their knowledge and
      understanding of basic disaster management principles and must play an active
      role in developing their institutional disaster plans.

PMID- 16425621
TI  - Mass casualty incidents: planning implications for trauma care.

PMID- 16425622
TI  - Triage: principles and practice.

PMID- 16425623
TI  - Blast trauma: the fourth weapon of mass destruction.
AB  - Injury from blast is becoming more common in the non-military population. This is
      primarily a result of an increase in politically motivated bombings within the
      civilian sector. Explosions unrelated to terrorism may also occur in the
      industrial setting. Civilian physicians and surgeons need to have an
      understanding of the pathomechanics and physiology of blast injury and to
      recognize the hallmarks of severity in order to increase survivorship. Because
      victims may be transported rapidly to the hospital, occult injury to gas and
      fluid containing organs (particularly the ears, bowel and lungs) may go
      unrecognized. Information surrounding the physical environment of the explosion
      (whether inside or outside, underwater, associated building collapse, etc) will
      prove useful. Most of the immediate deaths are caused by primary blast injury
      from the primary blast wave, but secondary blast injury from flying debris can
      also be lethal and involve a much wider radius. Liberal use of X-ray examination
      in areas of skin punctures will help to identify a need for exploration and/or
      foreign body removal. Biologic serum markers may have a role in identifying
      victims of primary blast injury and assist in monitoring their clinical progress.
      Tertiary blast injury results from the airborne propulsion of the victim by the
      shockwave and is a source of additional blunt head and torso trauma as well as
      fractures. Miscellaneous (quaternary) blast injury include thermal or dust
      inhalation exposure as well as crush and compartment syndromes from building
      collapse. Any explosion has the potential to be associated with nuclear, biologic
      or chemical contaminants, and this should remain a consideration for healthcare
      givers until proven otherwise.

PMID- 16425624
TI  - Urban bombing: a trauma surgeon's perspective.

PMID- 16425625
TI  - Nuclear, biological and chemical weapons: what the surgeon needs to know.

PMID- 16425626
TI  - Education and training in disaster medicine.

PMID- 16425627
TI  - Natural disasters: the surgeon's role.

PMID- 16425628
TI  - Disaster preparedness in Scandinavia.
AB  - Disaster preparedness in Scandinavia is being improved on the national level,
      with increased cooperation between the different countries following 9/11.
      However, focus so far has been largely directed against CBRN threats. The
      reduction of hospital beds along with centralisation of advanced care as well as
      financial strains will enforce a closer cooperation between the health boards.
      The federal health care authorities must have a clear-cut responsibility and
      mandate to coordinate the nations health care systems in peacetime disasters, and
      not only during war. This reorganisation has just merely begun.

PMID- 16425629
TI  - Comparison of methods to evaluate the energy supply in dairy herds.
AB  - Different methods to evaluate the nutritional and metabolic status in dairy herds
      are available. The aim of this study was to evaluate three different methods to
      assess the energy status of the herd: 1) the calculation of the energy balance of
      the herd with a new method based on the Swiss standard calculations, 2) the
      "efficiency of the feeding management" based on milk yield and milk protein
      content (%) obtained from DHI data, and 3) the percentage of cows per herd with
      an average milk yield (16-25 kg/day), but a low milk protein (< 3.2 %). The study
      included data from 47 farms enrolled in the herd reproduction survey program of
      the University of Berne, with a total of 653 cows included in one winter period.
      A correlation could only be seen between methods two and three. It is concluded
      that it is insufficient only to calculate the ration as an estimation of the
      energy status of the herd. A rough calculation of the ration is necessary to have
      an idea on the energy density. But the calculated ration seems to be considerably
      different from the amount of energy and nutrients of the diet finally absorbed by
      the cow. As the ingested ration is relevant for milk production and animal
      health, the relationship between milk yield and milk protein content as well as
      the percentage of cows with milk protein < 3.2% are considered to provide good
      information about the efficiency of the feeding management in dairy herds.

PMID- 16425630
TI  - Avian influenza A viruses in birds --an ecological, ornithological and
      virological view.
AB  - Avian influenza A viruses (AIV) are the causative agents of the presently most
      important poultry disease. Ten countries in Asia and several other countries in
      Eastern Europe suffer high losses from the lethal effects of these viruses of the
      H5N1 subtype. AIV of other subtypes cause in additional countries severe losses.
      The threat to health and well-being of the avifauna, domestic poultry and
      possibly mammals including humans are worldwide of major concern. The European
      Union reacted with a complete import ban on untreated meat, eggs, poultry
      products as well as free-living and pet birds. Extensive surveillance of free
      living birds and domestic poultry that is maintained in free-range and close to
      open waters were initiated in an attempt to gather information on the current
      status of infection with these viruses and to target appropriate countermeasures
      for the protection of domestic poultry (in-house keeping) and to safeguard food
      production for humans. Since the monitoring of free-living birds is labour
      intensive, costly, and time-consuming, only birds should be included in the
      monitoring programme that harboured in the past most if not all influenza A
      viruses. The birds of the order Anatiformes, family Anatidae, subfamilies
      Anserinae and Anatinae, provided 65.9 % of all avian AIV isolates. The
      cosmopolitan Common Mallard (Anas platyrhynchos) is the dominant species with the
      highest rate of isolations among all bird species. Second in frequency is the
      North-American Blue-winged Teal (Spatula discors). Consequently, free-living
      anatiform birds of the genera Anas and Spatula should comprise the main focus for
      the collection of cloacal and pharyngeal swabs. With the likely exception of the
      most recent H5N1 viruses, signs of disease were not recorded in AIV infected
      anatiform birds. AIV isolations were definitely less frequently obtained from
      birds of the orders Phasianiformes (including domestic chickens and turkeys),
      Charadriiformes (plovers and lapwings), Lariformes (gulls), Columbiformes
      (pigeons) and Psittaciformes (psittacines) and need less attention in sampling
      efforts. This review presents also data on taxonomy and most suitable means for
      isolation and typing of haemagglutinating viruses. The different frequencies of
      the detection of 16 haemagglutinin (HA) subtypes and 9 subtypes of neuraminidase
      (NA) surface antigens are composed on the basis of extensive literature
      retrievals. Both antigens occure in isolates at different frequencies. Only 103
      of all 144 possible HA x NA combinations were described so far. The AIV that
      contain the HA subtypes H3, H4, H6 are most frequently isolated whereas the AIV
      of the subtypes H5 and H7 were less frequently encountered. All other HAs are
      rather rare. AIV that possess the NA of the subtypes N2, N1, N8 and N3 are
      frequent and all other NAs are rarely detected.

PMID- 16425631
TI  - No detection of avian influenza A viruses of the subtypes H5 and H7 and isolation
      of lentogenic avian paramyxovirus serotype 1 in passerine birds during stopover
      in the year 2001 on the island Helgoland (North Sea).
AB  - A total of 543 migrating passerines were captured during their stopover on the
      island of Helgoland (North Sea) in spring and autumn 2001. They were sampled for
      the detection of avian influenza A viruses (AIV) subtypes H5 and H7, and for
      avian paramyxoviruses serotype 1 (APMV-1). The goal of the study was to examine
      the role of migrating birds as potential vectors for these zoonotic viral
      diseases. For virus detection samples were taken from a) short-distance migrants
      such as chaffinches (Fringilla coelebs, n = 131) and song trushes (Turdus
      philomelos, n = 169), and b) long-distance migrants such as garden warbler
      (Sylvia borin, n = 142) and common redstarts (Phoenicurus phoenicurus, n = 101).
      Virus detection was done on conjunctival, choanal cleft and cloacal swabs.
      Embryonated SPF chicken eggs were used to isolate and propagate virus followed by
      virus identification in a hemagglutination test, hemagglutination inhibition test
      and in an agar gel diffusion test. In none of the tested samples AIV was
      detected. Therefore, we conclude that the tested four species of passerines were
      infected by these pathogens. Six out of 543 birds (1.1 %) were found to carry non
      pathogenic and lentogenic strains of APMV-1. This indicates that the passerine
      species examined in this study may play only a minor role as potential vectors of
      APMV-1.

PMID- 16425632
TI  - Seasonal variation in selenium status of different classes of grazing goats in a
      semi-arid region of Pakistan.
AB  - The selenium status of three different classes of goats ((i) female lactating,
      (ii) female non-lactating, and (iii) male goats) grazing semi-arid pasture in the
      southern part of the Punjab province, Pakistan and that of selenium concentration
      of soil and dietary sources, ingested by those animals were investigated during
      two different seasons of the year (winter and summer). Soil, forage, feed, water
      from the pasture and blood plasma, urine, faeces, and (if applicable) milk from
      these goats were collected fortnightly. The samples were analyzed for selenium
      concentrations. Soil selenium showed both seasonal and sampling periods effect on
      its concentration while forage selenium was affected only by the seasonal
      changes. No significant effect of seasons or fortnights on feed selenium level
      was observed. In fecal samples selenium concentration in lactating and non
      lactating and plasma of male goats were affected by sampling periods. While fecal
      selenium in male goats showed significant effect on its concentration both
      seasonal and within fortnights. Severe deficient level of soil selenium during
      both seasons and marginal deficient level of forage selenium during summer were
      observed. Selenium concentrations in feed slightly exceeded the requirements of
      ruminants in feed during both seasons of the year. Plasma selenium concentrations
      in all goat classes were higher in winter than that in summer showing no seasonal
      or fortnight variation and its concentration was slightly lower in lactating
      goats as compared to other classes. On the bases of these results, it is
      concluded that overall selenium status of the goats based on plasma selenium
      concentration may be considered adequate mainly due to the mineral supplement
      provided all over the year, since soil and forage selenium concentrations were
      low to deficient.

PMID- 16425633
TI  - Effect of transport stress on physiological responses of male bovines.
AB  - Forty-eight slaughter bulls were transported by road in groups of eight for
      approximately 30 min, 3 h and 6 h in two replicates. Animal welfare during the
      transport process was assessed. Loadings and unloadings were evaluated with a
      scoring method. Heart rates were monitored at the farm before loading and during
      all stages of transport. Blood samples were taken from all animals a week before
      transport and at sticking and analysed in terms of haematological values:
      hematocrit, haemoglobin, red and white blood cells (RBC and WBC), differential
      WBC counts and neutrophil:lymphocyte ratio. Glucose, creatine kinase, lactate and
      cortisol were also determined. To evaluate differences in meat quality, pH and
      water-holding capacity (WHC) were measured 24 h after slaughter. The loading and
      unloading scores were very low (low stress) but were associated with changes in
      heart rate, especially loading. Animals recovered their resting heart rate during
      the journey in medium and long transports. On the other hand, animals transported
      around 30 min maintained an elevated heart rate during the whole journey. All
      animals showed a stress response with significantly higher (p < 0.05) levels of
      erythrocyte series, N:L ratio, glucose and lactate. Animals transported for 3 and
      6 hours had significantly (P<0.05) higher levels of cortisol than controls or 30
      min transports, without differences between control and the shortest journey.
      Different transport times did not influence meat quality. Under good conditions,
      the transport had a slight effect on welfare, meat quality or physiological
      parameters related with stress.

PMID- 16425634
TI  - [Detection of Coxiella burnetii in the air of a sheep barn during shearing].
AB  - Local epidemics of Q fever occur sporadically in Germany, mainly in rural
      residential communities. There is increasing evidence that these outbreaks, which
      are caused by Coxiella burnetii, are related particularly to the lambing season
      and shearing periods of nearby sheep holdings. It is assumed that this zoonotic
      agent is massively emitted from the placenta of infected ewes at birth and during
      shearing of wool contaminated with infected faeces of ticks. However, little is
      known about the airborne transmission and travel distance of this infectious
      agent, and only few attempts have been made to isolate it directly from the air.
      This paper describes for the first time the isolation and detection of C.
      burnetii in the air of an enclosed sheep barn during shearing of a herd which had
      tested positive for C. burnetii serologically and by PCR. Samples of inhalable
      dust samples were taken using I.O.M. samplers with glass fibre and polycarbonate
      filters at a flow rate of 2.5 l/min. The sampling time was nearly 4.5 h. Two
      sampling positions were set up on both sides of the shearing place at a distance
      of 3 m and 1.5 m above the ground. A third position with the same sampling
      equipment was not activated and served as a sampling and transport control. In
      the laboratory, the glass fibre filters were used to determine the dust
      concentration. The polycarbonate filters were treated in a specific breakdown
      procedure which inactivates PCR inhibitors, followed by amplification and
      sequencing of a specific DNA section of C. burnetii, which was found in the dust
      from both active sampling positions. The investigation clearly shows that the
      sampling and detection methods used in this small field study are suitable for
      the detection of C. burnetii in the air of sheep barns. The results confirm
      experimentally the high risk of airborne transmission of C. burnetii from sero
      positive sheep herds during shearing. However, little is known about the
      effective travel distance of infective airborne C. burnetii particles. There is
      an urgent need for more detailed investigations on the emission and airborne
      dispersion of infectious C. burnetii particles in order to improve our
      understanding of the health risks caused by this zoonotic agent originating from
      sheep herds.

PMID- 16425635
TI  - Incidence of multifactorial diseases in Estonian dairy herds--a survey.
AB  - An important precondition of a well-functioning dairy production is knowledge
      about the incidence of environmentally evoked non-infectious diseases in a
      particular herd, in the region and in the country as a whole. The aim of this
      study was to determine the incidence rate of environmentally evoked
      multifactorial diseases in Estonian dairy herds, and to compare the disease
      incidence in small (< or = 100 cows) and large herds (101-300 cows). The disease
      incidence was recorded by local veterinarians in twelve production units with a
      total of 33 cowsheds and about 5000 dairy cows. Fourteen disease groups were
      formed. In order to describe the range of disease incidence, the relative
      frequency of each group of diseases was determined, as well as the incidence
      rate. The 95 % confidence interval was applied in order to assess the reliability
      of the incidence rates. The most common disorders of Estonian dairy cows are
      udder diseases, followed by uterine infection, metabolic diseases and retained
      placenta. The disease incidence in Estonian dairy herds is similar to that of
      other European countries. Most of the diseases occur more often in small herds
      than in large herds.

PMID- 16425636
TI  - [Chronic rhonchopathy and obstructive sleep apnea syndrome: the role of
      otorhinolaryngology].

PMID- 16425637
TI  - [Research in the professional practice of the medical speciality].
AB  - Research has a very important role in the financial development of countries; it
      improves our life quality in all aspects and helps to face unexpected happenings.
      In Spain science has been left to a second plane and we feel necessary to reverse
      this situation. Amongst the different kinds of research (basic, clinical and
      translational) the two last ones are most interesting for clinical doctors.
      Training of the doctor in the research field helps to a better practice as the
      advances in research can be applied to clinical practice. There is a tendency for
      doctors to be involved less in research and it is very important to modify this
      situation. Research should start in Medical school and play an important role
      throughout the training period. Once training has concluded, those with capacity
      and interest in research should follow a 3-4 years training in the field and
      after that period they can undertake both clinical and research roles. Finally,
      in Spain our speciality needs to create specific research laboratories in those
      ENT departments in hospitals with adequate infrastructure to develop research.

PMID- 16425638
TI  - [Contribution of PET-CT imaging to head and neck oncology].

PMID- 16425639
TI  - [Aetiology and therapeutic considerations in chronic otitis media. Analysis of a
      5 year period].
AB  - BACKGROUND: This study provides an update on the bacterial aetiology of chronic
      otitis media in our area and the antibiotic sensivity of the bacteria involved in
      this pathology. METHODS: A retrospective study from 2000 to 2004, is carried out
      in a total of 127 adults diagnosed of chronic otitis media. Isolated bacteria
      were tested in vitro regarding sensitivity to fluoroquinolones, aminoglyosides,
      colistin, oxacilin, amoxicillin-clavulanic acid and cephalosporins. RESULTS: The
      most common pathogens we found were gram-negative organisms, especially
      Pseudomonas aeruginosa (47.7%), but among gram positive organisms,
      Staplhylococcus aureus, was involved in a significant number of infections (21%).
      The main findings that we found were as follows: 18% of P. aeruginosa strains
      were resistant to ciprofloxacin and 21.8% S. aureus strains were resistant to
      levofloxacin. 10.8% of S. aureus strains showed resistance to beta-lactams.
      CONCLUSION: The most important pathogen in our study was P. aeruginosa along with
      a variety of other gram-negative organisms and S. aureus. There is growing
      concern over the use of antibiotics and the development of resistance. We need to
      evaluate the antimicrobial activity by determining the susceptibility of a
      particular antibiotic against a specific bacterial strain.

PMID- 16425641
TI  - [Vestibular drop attacks or Tumarkin's otolithic crisis in patients with
      Meniere's disease].
AB  - INTRODUCTION: Drop attacks (DA) are a sudden fall that comes without warning and
      without loss of consciousness, with no associated neurological symptoms and
      normal neurological examination. A certain number of patients with Meniere's
      disease, develop Tumarkin's otolithic crisis or DA. The purpose of this study is
      to document the frequency and clinical features of DA in patients with Meniere's
      disease. METHODS: A cohort of 40 patients with "definitive" Meniere's Disease
      were followed up between six months and 12 years. The presence and
      characteristics of Tumarkin's otolithic crisis were recorded. RESULTS: Thirteen
      (32.5%) patients developed DA during the outcome of their Meniere's disease. The
      interval between the onset of typical symptoms of Meniere's disease and the DA
      ranged from less than one year to 18 years. The number of DA varied from 1 to 14.
      The attacks typically occurred in a flurry during a period of 1 year or less. Six
      patients had only one DA. No patient requiered treatment for the DA. CONCLUSIONS:
      Tumarkin's otolithic crisis in Meniere's disease are not uncommon. They can occur
      at any time during the course of the disease, generally in a flurry of less than
      one year. Most patients have a spontaneus remission of the DA.

PMID- 16425640
TI  - [Prevalence of the 35delG mutation in the GJB2 gene, del (GJB6-D13S1830) in the
      GJB6 gene, Q829X in the OTOF gene and A1555G in the mitochondrial 12S rRNA gene
      in subjects with non-syndromic sensorineural hearing impairment of
      congenital/childhood onset].
AB  - INTRODUCTION: The most frequent mutations responsible for non-syndromic hearing
      impairment in the Spanish population are the 35delG mutation in the connexin 26
      gene (GJB2), the del(GJB6-D13S1830) deletion in the connexin 30 gene (GJB6), the
      Q829X mutation in the otoferlin gene (OTOF), and the A1555G mutation in the 12S
      rRNA gene of the mitochondrial genome. PATIENTS AND METHODS: Screening for these
      mutations was performed on 38 patients from Cantabria with non-syndromic
      sensorineural hearing impairment of congenital/childhood onset. RESULTS: The
      A1555G mutation was detected in homoplasmy in 9 patients (23.7%). Three
      individuals were heterozygous for the 35delG mutation (7.9%). The heterozygous
      del(GJB6-D13S1830) deletion was present in one case (2.6%). One subject was
      homozygous for the Q829X mutation (2.6%). CONCLUSIONS: These four mutations are
      present in 36.8% of all cases of non-syndromic hearing impairment in our
      population.

PMID- 16425642
TI  - [Design and performance of a laboratory of olfactory test. Application of a new
      evaluation system].
AB  - BACKGROUND: To study and evaluate the factors that may influence on human
      olfactory sensibility to pyridine, we designed a specific laboratory with a new
      olfactory test to perform accurate measurements. METHODS: We have chosen pyridine
      as the test substance in our laboratory, for its frequent use of it in other
      studies. The special conditions of our laboratory are designed to allow
      individuals to access to this substance, controlling the different factors and
      parameters. With this purpose, we have validated the test and we have settled the
      reference threshold values with the score of thirty voluntary healthy patients
      between 20 and 40 years of age. RESULTS: We have used four different
      concentrations of pyridine to study the different factors of olfactory
      sensibility. 95% of cases detected the highest pyridine concentration and the
      remaining concentrations allowed us to know the olfactory sensibility of the
      studied population and the inferior thresholds. CONCLUSIONS: We have designed,
      performed and endorsed a laboratory for the study of olfaction. We have
      determined the sensibility of the studied population to different concentrations
      of pyridine that can be considered as a reference for further studies.

PMID- 16425643
TI  - [Suspicion of metastases in laryngeal carcinomas].
AB  - OBJECTIVE: To look for models predicting metastasis in laryngeal/hypopharyngeal
      carcinomas. DESIGN: Prospective study. PATIENTS: Sixty patients bearing laryngeal
      squamous cell carcinoma who were treated with curative purposes were followed
      prospectively with at least 10-year follow-up. PARAMETERS: Clinical (Staging,
      site, age, alcohol and smoking intake, surgery on the primary tumor, neck
      surgery) and pathological (size, number of metastatic lymph nodes, T and N
      staging, degree of differentiation, Jakobsson's and Glanz's scoring of
      malignancy, both scores in biopsies and surgical specimens) parameters were
      recorded in each case. METHODS: A multivariate analysis was performed to find out
      those parameters independently related to presence of metastases. RESULTS: The
      prospective study rendered tumor burden and Glanz's scoring from biopsies to be
      independently related with the presence of metastases. CONCLUSIONS: Malignancy
      grading systems must be included in laryngeal carcinoma patients' planning of
      neck treatment.

PMID- 16425644
TI  - [Acoustic and aerodynamic characteristics of the oesophageal voice].
AB  - OBJECTIVE: The aim of the study is to determine the physiology and
      pathophisiology of esophageal voice according to objective aerodynamic and
      acoustic parameters (quantitative and qualitative parameters). MATERIAL AND
      METHODS: Our subjects were comprised of 33 laryngectomized patients (all male)
      that underwent aerodynamic, acoustic and perceptual protocol. RESULTS: There is a
      statistical association between acoustic and aerodynamic qualitative parameters
      (phonation flow chart type, sound spectrum, perceptual analysis) among
      quantitative parameters (neoglotic pressure, phonation flow, phonation time,
      fundamental frequency, maximum intensity sound level, speech rate). CONCLUSION:
      Nevertheles, not always such observations bring practical resources to clinical
      practice. We consider that the facts studied may enable us to add, pragmatically,
      new resources to the more effective vocal rehabilitation to these patients. The
      physiology of esophageal voice is well understood by the method we have applied,
      also seeking for rehabilitation, improving oral communication skills in the
      laryngectomee population.

PMID- 16425645
TI  - [Congenital absence of the stapes suprastructure].
AB  - Congenital absence of the stapes suprastructure is an unusual anomaly,
      consequence of a developmental aberration involving partial absence of a derivate
      from the second branchial arch. Sometimes, exploratory tympanotomy may be the
      only mean of diagnosis when known conductive hearing loss is seen. This anomaly
      can appear isolated or associated to other major or minor anomalies. The
      treatment is surgical. We review the literature about the absence of the isolated
      stapes suprastructure.

PMID- 16425646
TI  - [Cochlear implants using the Ultracision harmonic scalpel].
AB  - We have evaluated the utility, indications and disadvantages of the Ultracision
      harmonic scalpel, in the cochlear implants, and his advantages compare to other
      electrocoagulation's systems. These aspects were evaluated in 50 cases of
      cochlear implants, made along the last years. We concluded that the Ultracision
      harmonic scalpel is indicated, mainly, in the otology field, in these situations
      in wich the cochlear implant is in the cochlea, and is mandatory the use of an
      electrocoagulation system. In this situation, the Ultracision harmonic scalpel
      was quick, safe and sure, and with many advantages, over the traditional scalpel
      and the bipolar diathermy.

PMID- 16425647
TI  - Improving nutrition knowledge.

PMID- 16425648
TI  - The Asia Pacific Academic Consortium for Public Heath (APACPH) the first ten
      years, from 1984 to 1994.
AB  - In January of 1984, five deans of schools of public health from Asia and the
      Pacific came together on the island of Kauai in Hawaii to formally establish the
      Consortium. The Consortium owes its cohesive strength through those first ten
      years of operation, to the dedicated faculty members in the fields of public
      health and community medicine whose overarching desire has been to seek
      representation of academic public health in the health decision making process
      affecting the positive promotion of health. By 1994 the Consortium found itself
      recognized on a world wide basis in the field of global health with what was
      described as having: "A great potential for extending the effectiveness of
      community and public health". "The author, a founding Dean feels that the
      Consortium's commitment is to shape rather than to await the future of health
      status improvement for the citizens of the Asia-Pacific region.

PMID- 16425649
TI  - Factors affecting nutritional status of Malaysian primary school children.
AB  - This paper investigates the nutritional status of a randomly selected cohort of
      school children and the factors affecting it. This random survey was conducted in
      the state of Selangor, involving 1,405 primary students (aged 9-10 years from 54
      national primary schools). Physical examination was carried out on all the
      students. Information on the students was also obtained from the parents. Blood
      samples were taken by using the finger pricking technique. Body mass index (BMI)
      was used as a measure of physical growth. The students were mainly from urban
      areas (82.9%). The mean age was 9.71 years and a higher proportion was females
      (51%). Malays constituted 83.6%, Indians 11.6% and Chinese 4.2% of the study
      population. The mean weight and height were 32.30 kg and 135.18 cm respectively.
      The mean BMI was 17.42 kg/m2, with 1.2% of the students underweight, 76.3% normal
      BMI, 16.3% overweight and 6.3% were obese. Nutritional status was significantly
      related to blood pressure, history of breast feeding, eating fast food, taking
      canned/bottled drinks, income and educational level of parents. Significant
      differences in nutritional status between sexes and locations (rural/urban) were
      also found. The prevalence of overweight and obese children was of concern. There
      is thus an urgent need for the School Health Program to periodically monitor the
      school children's eating habits and physical growth. Appropriate counselling on
      nutritional intake and physical activities should be given not only to
      schoolchildren but also to their teachers and parents or caregivers.

PMID- 16425650
TI  - Effects of nutritional status on academic performance of Malaysian primary school
      children.
AB  - Numerous factors are known to affect the academic performance of students. These
      include prenatal conditions, birth conditions, postnatal events, nutritional,
      socio-economic factors and environmental factors. This paper examines the
      nutritional status and its relationship with academic performance of 9-10 years
      old primary school children recruited randomly in Selangor, Malaysia. A standard
      self-administered questionnaire was utilized to obtain pertinent information and
      a face-to-face interview was also conducted with the parents. Results of the
      academic performances were extracted from the students' report cards. The
      intellectual performance was assessed using Raven's Coloured Progressive
      Matrices. Physical examination was also conducted on these students by doctors.
      Overall 1,405 students and 1,317 parents responded to the survey. Of these 83.6%
      were Malays, 11.6% Indians, and 4.2% Chinese. The majority of them (82.9%) were
      from urban areas. The female: male ratio was 51:49; mean age was 9.71 years. The
      mean height and weight were 32.3 kg and 135.2 cm respectively. Their mean BMI was
      17.42 kg/cm2, with 0.9% underweight, 76.3% normal BMI, 16.3% overweight, and 6.3%
      obese. Academic performance was significantly correlated with breast feeding,
      income and educational level of their parents, BMI, and whether they have been
      taking breakfast. There was a weak correlation between presence of anaemia and
      intellectual performance. Improving the socio-economic status of the parents will
      lend a helping hand in the academic performance of the students. Since breast
      feeding is associated with better academic and intellectual performance it must
      be emphasized, particularly to expectant mothers in the antenatal clinics.

PMID- 16425651
TI  - Dietary glycemic load and macronutrient intake in healthy Italian children.
AB  - The objective is of this study is to examine the relationship of dietary glycemic
      load (GL) and overall glycemic index (OGI) with macronutrients intake, body mass
      index (BMI) and insulin sensitivity in healthy children. The subjects comprised
      of 105 healthy non-obese eight-years old children, 60 boys and 45 girls. A Food
      Frequency Questionnaire (FFQ) evaluating dietary habits, GL and OGI. Insulin
      sensitivity was evaluated by the homeostatic model assessment (HOMA). GL was
      positively associated with dietary total (correlation coefficient, r=0.57) and
      starch (r=0.67) carbohydrates, daily consumption of pasta and white bread, cooked
      potatoes, bakery products and cookies, and negatively with dietary fats (r=
      0.52). OGI was positively associated with daily consumption of white bread and
      cookies, and negatively associated with soluble carbohydrates (r=-0.35), and
      consumption of fibres, proteins, fruit, legumes and carrots. No significant
      association was found of GL or OGI with BMI or insulin sensitivity. In healthy
      children, GL and OGI may represent a useful indicator of quality of diet.

PMID- 16425653
TI  - Identifying competencies for Australian health professionals working in
      international health.
AB  - A profile of the roles performed by Australian health professionals working in
      international health was constructed to identify the core competencies they
      require, and the implications for education and training of international health
      practitioners. The methods used included: literature review and document analysis
      of available training and education; an analysis of competencies required in job
      descriptions for international health positions; and consultations with key
      informants. The international health roles identified were classified in four
      main groups: Program Directors, Program Managers, Team Leaders and Health
      Specialists. Thirteen 'core' competencies were identified from the job analysis
      and key informant/group interviews. Contributing to international health
      development in resource poor countries requires high level cultural,
      interpersonal and teamwork competencies. Technical expertise in health
      disciplines is required, with flexibility to adapt to new situations.
      International health professionals need to combine public health competencies
      with high level personal maturity to respond to emerging challenges.

PMID- 16425652
TI  - Nutritional and mental health status of Afghan refugee children in Peshawar,
      Pakistan: a descriptive study.
AB  - The study sought to ascertain and describe the physical and mental health states
      of Afghan refugee children after the terrorist attack on September 11, 2001 in
      the US and the aerial bombing of Afghanistan that followed. A cross-sectional
      survey was carried out in four refugee camps in Peshawar, Pakistan from February
      to March 2002, and comparisons among camps were made. A total of 70 males (mean
      age SD = 9.81 +/- 1.98 years old) and 30 females (7.94 +/- 2.07) answered a self
      developed questionnaire on demographic data, traumatic events experience, living
      environment in the camps, and physical and mental health, through interviews.
      Anthropometric measures were measured and physical symptoms including anaemia and
      edema were assessed. Severe malnutrition was not shown and there were no
      significant differences in most nutritional and physical states among the camps.
      Nevertheless, in the newer camps more children experienced war related traumatic
      events. Mental symptoms were prevalent in all camps, though the characteristics
      of the symptoms differed among the camps.

PMID- 16425654
TI  - The determinants of long-term care utilization and equity of access to care among
      older adults in Dong-Ku of Incheon Metropolitan city, South Korea.
AB  - Under the current health care system, around three percent of the elderly remain
      uninsured. Based on the 2003 Dong-Ku Health Status Survey and the Aday and
      Andersen Access Framework, the present study examined the social and behavioral
      determinants of long-term care utilization and the extent to which equity in the
      use of long-term care services for the elderly has been achieved. The results
      indicate that universal health insurance system has not yielded a fully equitable
      distribution of services. Type of coverage and resource availability do not
      remain predictors of long-term care utilization. The data suggest that a
      universal health insurance system exists in South Korea with significant access
      problems for the population without insurance. Access differences also arise from
      obstacles in expanding the scope and level of plan benefits due to financial
      disparity among insurers. Health policy reforms must continue to concentrate on
      extending insurance coverage to the uninsured and establishing long-term
      insurance system for the elderly.

PMID- 16425655
TI  - Thailand's national death registration reform: verifying the causes of death
      between July 1997 and December 1999.
AB  - A fundamental aspect of public health is the accuracy of death certification.
      Assessing the death registration system is a step toward improving the quality of
      death reporting. Thailand implemented a more rigorous and informative pilot death
      registration system in March 2001 in 18 provinces, followed by nationwide
      implementation in August 2003. Since Thailand is an industrializing nation, its
      experiences will be of interest to other developing nations planning similar
      reforms. The causes of all deaths in the 15 provincial pilot projects (of
      Thailand's 76 provinces) and a random sampling in Bangkok were investigated
      between July 1997 and December 1999. Health workers interviewed close relatives
      and three medical doctors reviewed hospital records to verify the causes of
      death. We were able to interview 78% of the relatives (i.e. 47,632 in number).
      Three-quarters (76%) of the deceased had sought prior medical care; 41% died in
      hospital and 54% at home. The overall agreement between the causes of death in
      our survey vs. that reported on the death certificate was 29%. The highest
      agreement was for: 'Ill-defined' causes (33%), 'Cancer and Tumors' (17%),
      'External Causes' (16%), and 'Infectious Diseases' (10%). Considering the
      different patterns among age groups and sex, hypertension with stroke, cancer of
      the liver and bile duct, and HIV infection, were the highest ranking causes among
      females. Infectious diseases (especially HIV/AIDS), hypertension with stroke and
      accidents, were the leading causes of deaths among males. External causes were
      highest among children and young adults.

PMID- 16425656
TI  - Utilisation of non-steroidal anti-inflammatory drugs (NSAIDs) through community
      pharmacies in Malaysia.
AB  - This study was conducted to evaluate the use of non-steroidal anti-inflammatory
      drugs (NSAIDs) by consumers who obtained these drugs from community pharmacies.
      Factors that influenced community pharmacists in their choice of NSAIDs were also
      determined. Personal interviews were conducted on consumers who visited the 25
      participating community pharmacies throughout Malaysia. Of the 389 respondents,
      49% requested for an NSAID by name, 42% asked the pharmacist to recommend a
      medication and 9% had a doctor's prescription. NSAIDs were mainly purchased for
      joint/shoulder pain and the most commonly dispensed was diclofenac. Elderly
      respondents were more likely to be dispensed a selective COX-2 inhibitor than
      those below 60. NSAIDs were recommended based mainly on the pharmacist's
      perception of their efficacy, cost and safety. Community pharmacists play an
      important role in assisting patients in choosing the most appropriate NSAID for
      their health problems.

PMID- 16425657
TI  - Exploratory study on psychosocial impact of the severe acute respiratory syndrome
      (SARS) outbreak on Chinese students living in Japan.
AB  - The aim of this study is to explore the impact of the 2003 SARS outbreak on
      Chinese students living in Japan. A cross-sectional study was conducted using a
      semi-structured questionnaire. The participants were recruited at multiple
      locations at the University of Tokyo, Japan. The results showed approximately 60%
      (96/161) of the respondents felt an impact of SARS on college life; they had
      experienced SARS-related fear, worry, depression as well as social discrimination
      and had taken SARS prevention measures for daily protection in Japan during the
      epidemic. The magnitude of the impact was associated with socio-demographic
      factors, including their age, specialty, area of previous residence in China and
      length of stay in Japan. The findings suggest that the SARS outbreak had a
      psychosocial impact on the Chinese students living in Japan, even though none of
      them had SARS. Social support tailored for these foreign students should be
      provided during such a disease outbreak.

PMID- 16425658
TI  - Smoking among secondary school students in Negeri Sembilan, Malaysia.
AB  - This study was done to determine the prevalence of smoking and factors
      influencing cigarette smoking among secondary school students in Negeri Sembilan,
      Malaysia. This is a cross-sectional school survey conducted on 4500 adolescent
      students based on a structured questionnaire. Data was collected using the
      supervised self-administered questionnaire the Youth Risk Behaviour Surveillance
      in the Malaysian National Language Bahasa Malaysia. The prevalence of smoking
      among the students was 14.0%. About a third of the students (37.8%) started
      smoking at 13 to 14 years of age. The prevalence of smoking among the male
      students was higher (26.6%) compared to the female students (3.1%). Adolescent
      smoking was associated with (1) sociodemographic factors (age, ethnicity,
      rural/urban status); (2) environmental factors (parental smoking, staying with
      parents); (3) behavioural factors (playing truant and risk-taking behaviours such
      as physical fighting, drug use, alcohol use, sexual activity, lack of seatbelt
      use, riding with a drunk driver); (4) lifestyle behaviours (being on diet and
      lack of exercise); (5) personal factors (feeling sad and suicidal behaviours). In
      conclusion, smoking is a major problem among Malaysian adolescents. Certain
      groups of adolescents tend to be at higher risk of smoking. This problem should
      be curbed early by targeting these groups of high risk adolescents.

PMID- 16425659
TI  - Risk of cancer as a result of community exposure to gasoline vapors.
AB  - The Tranguch Gasoline Spill leaked 50,000-900,000 gallons of gasoline from
      underground storage tanks, potentially exposing an area of Hazle Township and
      Hazleton, Pennsylvania, to chronic low levels of benzene since at least 1990. A
      retrospective cohort study of 663 individuals representing 275 households
      assessed whether affected residents were at increased risk for cancer from 1990
      2000 compared with the Pennsylvania populace. Age-adjusted standard incidence
      ratios (SIRs) were calculated using Pennsylvania rates to determine expected
      numbers. The age-adjusted SIR for the gasoline-affected area was 4.40 (95%
      confidence interval: 1.09-10.24) for leukemia. These results suggest an
      association between living within the area affected by the Tranguch Gasoline
      Spill and increased risk for leukemia.

PMID- 16425660
TI  - Effects of ambient air pollutants on asthma medication use and wheezing among
      fourth-grade school children from 12 Southern California communities enrolled in
      The Children's Health Study.
AB  - To investigate the effects of 12 monthly average air pollution levels on monthly
      prevalence of respiratory morbidity, the authors examined retrospective
      questionnaire data on 2034 4th-grade children from 12 Southern California
      communities that were enrolled in The Children's Health Study. Wheezing during
      the spring and summer months was associated with community levels of airborne
      particulate matter with a diameter < or = 10 microm (PM10) (odds ratio (OR) =
      2.91; 95% confidence interval (CI) = 1.46-5.80), but was not associated with
      community levels of ozone, nitrogen dioxide, PM2.5 (diameter < or = 2.5), nitric
      acid, or formic acid. Logistic regression was performed on data stratified into
      two seasonal groups, spring/summer and fall/winter. Among asthmatics, the monthly
      prevalence of asthma medication use was associated with monthly levels of ozone,
      nitric acid, and acetic acid (OR = 1.80 [95%CI = 1.19-2.70]; OR = 1.80 [95%CI =
      1.23-2.65]; OR = 1.57 [95% CI = 1.11-2.21]; respectively). Asthma medication use
      was more prevalent among children who spent more time outdoors--with
      consequential exposure to ozone--than among children who spent more time indoors
      (OR = 3.07 [95%CI = 1.61-5.86]; OR = 1.31 [95%CI = 0.47-2.71]; respectively). The
      authors concluded that monthly variations in some ambient air pollutants were
      associated with monthly respiratory morbidity among school children.

PMID- 16425661
TI  - Systemic vasculitis and prior recent exposure to organic solvents: report of two
      cases.
AB  - The authors describe two patients with systemic vasculitis and prior occupational
      exposure to organic solvents. Systemic vasculitis should be considered a sentinel
      event for such exposures.

PMID- 16425662
TI  - Endotoxin exposure and respiratory symptoms in the cotton textile industry.
AB  - One hundred fourteen male employees of a cotton spinning mill in western Germany
      participated in a cross-sectional study, the purpose of which was to clarify the
      dose effect of endotoxin exposure on respiratory symptoms. Airborne endotoxin
      exposures were classified as low (< or = 100 endotoxin units [EU]/m3), medium (>
      100-450 EU/m3), or high (> 450 EU/m3), on the basis of endotoxin activity in the
      Limulus amoebocyte lysate assay. Age- and smoking-adjusted odds ratios (ORs) and
      confidence intervals (CIs) were estimated. The dose-response relationship between
      current endotoxin exposure and prevalence of wheezing (medium: OR = 2.15, 95% CI
      = 0.48-9.62; high: OR = 5.49, 95% CI = 1.17- 25.81) and cough (medium: OR = 2.11;
      95% CI = 0.59-7.56; high: OR = 3.93; 95% CI = 1.02-15.12) was significant (test
      for linear trend: p values = 0.020 and 0.040, respectively). The association
      between exposure and wheezing was stronger among atopic workers. The higher
      prevalence of chest tightness and shortness of breath among workers with medium
      and high current endotoxin exposure did not reach statistical significance. The
      results suggested that there was a dose-dependent increase in bronchial symptoms,
      with significant effects occurring at exposures that exceeded 450 EU/m3.

PMID- 16425663
TI  - Extrapolations and public policy.

PMID- 16425664
TI  - Predicting premature mortality from new power plant development in Virginia.
AB  - The authors estimated the number of premature deaths from particulate matter less
      than 2.5 microm (PM2.5) that would result from making 29 proposed fossil fuel
      power plants in Virginia operational. We used a U.S. Environmental Protection
      Agency air quality model (Climatological Regional Dispersion model) to calculate
      changes in ambient concentrations of PM2.5 and Cox proportional hazard modeling
      to calculate the resulting premature mortality. The model predicted that if all
      29 plants were operational, PM2.5 concentrations would rise in 271 counties
      across 19 states 5 and increased average annual PM2.5 concentrations would result
      in a rate of 17 deaths per 37,900,026 people aged 30 yr and older (0.45 deaths
      per million, 95% confidence interval = 0.31, 0.59) per year by the end of 2004,
      increasing thereafter. Over a 6 yr period, 104 cumulative excess deaths would
      occur due to operations of these proposed plants. The authors recommend that
      precautionary principles be considered when policy decisions related to energy
      production from fossil fuels are made.

PMID- 16425665
TI  - The genome: five years on.

PMID- 16425666
TI  - Steroid therapy for exudative age-related macular degeneration: bridging the gap
      until a cure is found.

PMID- 16425667
TI  - Nitrone spin on cerebral ischemia.
AB  - Clinical trials with radical scavenging antioxidants have shown little or no
      benefit in the treatment of ischemic stroke. The spin trap nitrones covalently
      bind with short-lived reactive radicals to inactivate them for longer than the
      conventional scavenging antioxidants. One of these agents, NXY-059, is effective
      in animal models of cerebral ischemia, and is in phase III clinical trials for
      ischemic stroke by AstraZeneca, under license from Renovis. Second-generation
      nitrones (azulenyl nitrones) have also been described and shown to be
      neuroprotective in animal models. Thus, at last, it seems that antioxidants that
      are potent enough to have considerable potential for the treatment of cerebral
      ischemia are in development.

PMID- 16425668
TI  - Drugs in development for Parkinson's disease: an update.
AB  - The current development of emerging pharmacological treatments for Parkinson's
      disease (PD), front preclinical to launch, is summarized. Advances over the past
      year are highlighted, including the significant progress of several drugs through
      various stages of development. Several agents have been discontinued from
      development, either because of adverse effects or lack of clinical efficacy. The
      methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B
      inhibitor rasagiline have both been launched. With regard to the monoamine re
      uptake inhibitors, many changes have been witnessed, with new agents reaching
      preclinical development and pre-existing ones being discontinued or having no
      development reported. Of the dopamine agonists, many continue to progress
      successfully through clinical trials. Others have struggled to demonstrate a
      significant advantage over currently available treatments and have been
      discontinued. The field of non-dopaminergic treatments remains dynamic. The
      alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists
      remain in clinical trials. Trials of the neuronal' synchronization modulator
      levetiracetam are at an advanced stage, and there has also been a new addition to
      the class (ie, seletracetam). There has been a change in the landscape of
      neuroprotective agents that modulate disease progression. Candidates from the
      classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors
      have been discontinued, or no development has been reported, and the mixed
      lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other
      drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein
      oligomerization inhibitors, remain in development.

PMID- 16425669
TI  - The mechanism of action of gabapentin in neuropathic pain.
AB  - Neuropathic pain is a common and potentially treatable cause of considerable
      lifelong morbidity. Effective pharmacological treatments are scarce, but one
      group of drugs that has shown promise is the antiepileptics. Gabapentin has
      become popular as a first-line treatment for neuropathic pain because of its
      efficacy as an antineuropathic agent and relatively benign side-effect profile.
      However, its mechanism of action is far from clear. This review discusses the
      available evidence for the postulated mechanisms of action of gabapentin.
      Understanding the mechanism of action of this agent may well lead to the
      development of safer and more effective antineuropathic drugs.

PMID- 16425670
TI  - 5-HT(1A) receptor activation: new molecular and neuroadaptive mechanisms of pain
      relief.
AB  - Guided by an understanding of signal transduction in pain-processing systems,
      high-efficacy 5-hydroxytryptamine (5HT)1A receptor activation, by means of F
      13640, has been discovered as a new molecular mechanism of pain relief in
      laboratory animals, inducing two neuroadaptive phenomena. Firstly, this
      activation cooperates with nociceptive stimulation, paradoxically causing
      analgesia, and secondly, inverse tolerance develops so that the resulting
      analgesia grows rather than decays. As an apparent result of these novel
      neuroadaptive mechanisms, F-13640 exerts an analgesic action in rat models of
      acute, tonic and chronic nociceptive pain that is rivaled only by large doses of
      high-efficacy mu-opioid receptor agonists. In models of neuropathic allodynia of
      peripheral or central origin, chronic F-13640 administration causes an analgesia
      that surpasses that observed with morphine or other agents exemplifying other
      central nervous system drug mechanisms of pain relief (e.g., ketamine, imipramine
      and gabapentin). Indeed, F-13640 produces long-lasting, preemptive and, most
      remarkably, curative-like actions in neuropathic allodynia. Although awaiting
      proof-of-concept evidence in humans, high-efficacy 5-HT(1A) receptor activation
      may uniquely challenge the opioids for pain therapy.

PMID- 16425672
TI  - Does VEGF represent a potential treatment for amyotrophic lateral sclerosis?
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
      The pathogenesis of ALS is unclear and there is no effective treatment. Vascular
      endothelial growth factor (VEGF) is a cytokine that has a protective function via
      angiogenic, neurotrophic, gliotrophic and anti-apoptotic activity. Data indicate
      that VEGF can inhibit neurodegeneration in ALS and may have therapeutic potential
      in this disease. The use of gene therapy to deliver VEGF into the central nervous
      system is being evaluated.

PMID- 16425671
TI  - Glycine receptors: a new therapeutic target in pain pathways.
AB  - Although glycine receptor Cl- channels (GlyRs) have long been known to mediate
      inhibitory neurotransmission onto spinal nociceptive neurons, their therapeutic
      potential for peripheral analgesia has received little attention. However, it has
      been shown that alpha3-subunit-containing GlyRs are concentrated into regions of
      the spinal cord dorsal horn where nociceptive afferents terminate. Furthermore,
      inflammatory mediators specifically inhibit alpha3-containing GlyRs, and deletion
      of the murine alpha3 gene confers insensitivity to chronic inflammatory pain.
      This strongly implicates GlyRs in the inflammation-mediated disinhibition of
      centrally projecting nociceptive neurons. Future therapies aimed at specifically
      increasing current flux through alpha3-containing GlyRs may prove effective in
      providing analgesia.

PMID- 16425673
TI  - Ispronicline (Targacept).
AB  - Targacept (formerly a subsidiary of RJ Reynolds) is developing ispronicline, the
      lead in a series of nicotinic acetylcholine (nACh) ligands, as a potential oral
      treatment for cognitive impairment, including a variety of non-Alzheimer's
      dementias. In July 2005, Targacept was preparing for a phase II study in patients
      with mild-to-moderate Alzheimer's disease.

PMID- 16425674
TI  - AEOL-10150 (Aeolus).
AB  - AEOL-10150, a small-molecule antioxidant analogous to the catalytic site of
      superoxide dismutase, is under development by Aeolus (formerly Incara) as a
      potential subcutaneous treatment for amyotrophic lateral sclerosis (ALS), stroke,
      spinal cord injury, lung inflammation and mucositis. The compound is currently
      undergoing a phase I clinical trial for ALS. In October 2005, the company had
      applied for Fast Track status, and planned to submit a special protocol
      assessment for a pivotal phase II/III trial.

PMID- 16425675
TI  - Vivitrex (Alkermes/Cephalon).
AB  - Vivitrex, an injectable, sustained-release formulation of the opioid antagonist
      naltrexone, is being developed by Alkermes and Cephalon for the potential once
      monthly treatment of alcoholism and opiate use disorder. Alkermes and Cephalon
      are currently awaiting Food and Drug Administration review of the Vivitrex new
      drug application, which was granted Priority Review in May 2005.

PMID- 16425676
TI  - Adolescent motherhood may not be a bad thing.

PMID- 16425677
TI  - Trainee midwife launches independent campaign for pound 10,000 student bursary.

PMID- 16425678
TI  - Curtains for the old delivery suite.

PMID- 16425679
TI  - Creating normality in a high-risk pregnancy.

PMID- 16425680
TI  - In praise of the NICE guidelines for induction.

PMID- 16425681
TI  - One mother, one midwife.

PMID- 16425682
TI  - An interview with Robbie Davis-Floyd. Interview by Sarah Wickham.

PMID- 16425683
TI  - A matter of judgement.

PMID- 16425684
TI  - Unpacking sweeping policies.

PMID- 16425685
TI  - Coagulation disorders (3). Stroke: prevention and management.

PMID- 16425686
TI  - Midwifery basics: complications in pregnancy (4). Breech birth.

PMID- 16425687
TI  - The expert witness (1). Wanted: expert witnesses.

PMID- 16425689
TI  - NHS redress--progress and problems.

PMID- 16425688
TI  - What kind of midwife are you?

PMID- 16425690
TI  - Manslaughter--how did we get here?

PMID- 16425691
TI  - 20th century gods: the rise and fall of the medical priesthood.

PMID- 16425692
TI  - Damages for the "unwanted" child: time for a rethink?

PMID- 16425693
TI  - Swimming against the stream: major changes to GMC's complaints procedure a
      concern for doctors.

PMID- 16425694
TI  - Serious professional misconduct.

PMID- 16425695
TI  - Liability of the employer, the hospital or other medical institution for the
      wrongdoing of employees.

PMID- 16425696
TI  - Comparing mission statement content in for-profit and not-for-profit hospitals:
      does mission really matter?
AB  - In this article, the author examined the content of mission statements in both
      the for-profit and not-for-profit hospital sectors. He used content analysis to
      compare and contrast the existence and frequency of words or phrases found in the
      mission statements of each sector. In particular, he analyzed the following three
      concepts: cost, access, and quality. The author found no significant differences
      in mission statement content across these three concepts when he compared
      investor-owned (for-profit) and nongovernmental not-for-profit hospitals. The
      results of this study suggest that the hospital industry lags behind other
      sectors in the design and development of thorough and complete mission
      statements. Hospital executives are encouraged to devote more time to the
      construction of hospital-specific and comprehensive mission statements that will
      provide important information for stakeholders, while simultaneously capturing
      the organization's unique purpose and niche in the competitive healthcare
      environment.

PMID- 16425697
TI  - Analysis of the effect of conflict-management and resolution training on employee
      stress at a healthcare organization.
AB  - Conflict is inevitable and can be both positive and negative. Although it is
      impossible, and probably not wise, to eliminate conflict, it is prudent for
      healthcare organizations to provide direct instruction in conflict-management
      training. In this study, 23 supervisors and managers in a local healthcare
      organization participated in two 3-hour sessions designed to teach practical
      conflict-management strategies immediately applicable to their workplace duties
      and responsibilities. A comparison of pretest and posttest measures indicates
      statistically significant differences in four areas and suggests a positive
      influence of the brief intervention.

PMID- 16425698
TI  - Department directors' perceptions of the roles and functions of hospital
      chaplains: a national survey.
AB  - A national survey of hospital directors of medicine, nursing, social services,
      and pastoral care was conducted to obtain opinions about the importance of
      various chaplain roles. On average, directors in all four disciplines rated three
      of the seven chaplain roles (grief and death, prayer, and emotional support) to
      be "very" to "extremely" important. Most of the others roles were rated between
      "moderately" and "very" important (religious services-rituals consultation and
      advocacy, community liaison-outreach). Several significant differences were found
      among disciplines, as physicians rated the importance of most chaplains' roles
      lower than did other disciplines. Overall, there was a tendency for directors in
      smaller hospitals, especially those with fewer than 100 patients, to place less
      importance on most of the chaplain roles investigated here.

PMID- 16425699
TI  - Physician entrepreneurship and hospitals--Part 2.

PMID- 16425700
TI  - A closer look at the concept, historical overview, and value of direct-to
      consumer advertising of prescription drugs.

PMID- 16425701
TI  - The strength of the human spirit.

PMID- 16425703
TI  - IMS provides testimony to Medical Malpractice Interim Study Committee.

PMID- 16425702
TI  - Iowa insurance division--regulatory protections for physicians and patients.

PMID- 16425704
TI  - Student and teacher.

PMID- 16425706
TI  - The most important decade.

PMID- 16425705
TI  - Narcotics: prescription for trouble.

PMID- 16425707
TI  - Medicare part D--what doctors need to know.

PMID- 16425708
TI  - Wellsville empowers kids and families.

PMID- 16425710
TI  - [Cutaneous mucormycosis and diabetes: about one observation].
AB  - Mucormycosis is a rare opportunistic infection but a fulminant disease. Varying
      clinical forms have been described, including cutaneous localisations which are
      mainly observed in diabetic and burned patients. The cutaneous lesions induced by
      the mucormycosis affection are often atypical and gangrenous. We report a case of
      cutaneous mucormycosis in a Tunisian patient with diabetic ketoacidosis. He
      developed cutaneous necrotic lesions at the low limb. The diagnosis of
      mucormycosis was not initially evoked but tardily confirmed by identifying
      mucorale hyphae in tissue sections and Rhizopus oryzae in the sample culture. The
      treatment consisted of an extensive surgical debridement associated with
      intravenous perfusion of amphotericin B. The patient had a fatal outcome.

PMID- 16425709
TI  - [The use of dried blood spots for HIV-antibody testing in Sahel].
AB  - Undertaking a HIV seroepidemiological survey in Sahel is logistically
      problematic, since countries like Niger or Mali are very large with scattered
      populations and harsh climatic conditions. Therefore, the replacement of serum
      samples by whole blood dried on filter papers has been studied for HIV-antibody
      testing with commercial kits that are commonly used. In Niger, two tests ELISA
      (Genscreen HIV1/2 version 2, Vironostika HIV Uni-Form II Ag/Ab) and two rapid
      tests (Determine HIV1/2 et Immunocomb II HIV1&2 Bispot) were used to compare the
      dried blood spots and serum samples from 43 control individuals. Both ELISAs gave
      an excellent correlation (r = 0.99 et r = 0.98) between the dried blood spots and
      serum absorbance values. Using the rapid tests, the HIV status was found 100%
      concordant with dried blood spots and serum samples. An algorithm using three out
      of the four mentioned tests was defined then validated on the dried blood spots
      of 163 control individuals (100% concordant). In conclusion, dried blood spots
      may accurately and profitably replace serum samples for the serodiagnosis of HIV
      infection and for mass serosurveys in Sahel.

PMID- 16425711
TI  - [Rhinofacial entomophthoromycosis. About two new cases in Mayotte].
AB  - Conidiobolus entomophthoromycosis is a rare mycosis due to an ubiquitary telluric
      fungus. Although the organism is found around the world, it is more concentrated
      in warm, wet climates. Cases have been described in West Africa, Australia, South
      America and India. Conidiobolus spp was also to be found in animal like horse.
      The transmission mode of Conidiobolus has not been established but probably
      occurs via inhalation of fungal spores covering the nasal mucous membrane or from
      a minor trauma such as an insect bite. The clinical syndromes include intranasal
      tumour, nasal obstruction, broadening of the nose bridge, paranasal sinuses,
      cheeks and upper lip. Diagnostic is made by demonstrating distinctive non-septate
      hyphea with surrounding eosinophilic sleeve (Splendore-Hoeppli phenomenom) in
      tissue sections. We report here two cases contracted in Comoro Islands. The first
      one was a 26 year-old man treated by amphotericin B during six weeks and then by
      itraconazole, with a clear improvement. The second one was a 37 year-old woman.
      She has been treated by amphotericin B, subsequently by imidazoles. There was a
      clear benefit on life duration, but the results for aesthetic aspect are not
      satisfactory. In the discussion, we review treatment efficacy and failure; in
      fact, surgery which includes removal of infected tissue and reconstructive
      procedures, is seldom curative. Several combinations of drugs have been used with
      different degrees of success. Nevertheless imidazoles remain more efficient than
      amphotericin B.

PMID- 16425712
TI  - [Congenital cutaneous candidiasis: a case report and review].
AB  - The aim of this article is to report a case of congenital cutaneous candidiasis
      (CCC). We describe the clinical features and emphasize the role of laboratory
      testings to assess diagnosis in the newborn and to prevent this condition by
      screening vaginal candidiasis in pregnant women. A full-term, 3500-g male was
      born by spontaneous vaginal delivery to a 30-year-old healthy woman. On physical
      examination, he was a well-developed, vigorous newborn. Since the first hours of
      his life he presented erythematous maculae diffusely distributed on the skin and
      pustules overlying areas of confluent macular erythema on his trunk and
      extremities. The palms and soles were not affected. Neither oral thrush nor peri
      anal lesions have been observed. The rest of the physical examination was normal.
      Microscopic examination of skin scrapings showed the presence of many yeasts and
      the culture permitted the identification of a strain of Candida albicans.
      Precocity and extent of the cutaneous signs attest a congenital cutaneous
      candidiasis and eliminate the other skin diseases of similar clinical symptoms.
      Topical antifungal therapy (econazole) was given and the cutaneous lesions
      disappeared after 20 days. CCC appears to be acquired in utero by the ascension
      of organisms from an infected vagina into the uterine cavity. This condition is
      preventable with systematic screening and treatment of vulvo-vaginitis due to
      Candida albicans in pregnant women, The important role played by the laboratory
      of mycology remains essential.

PMID- 16425713
TI  - [Epidemiological, clinical and parasitological data about canine leishmaniasis in
      Tunisia].
AB  - Epidemiological, clinical and parasitological data concerning canine
      leishmaniasis were collected in two Tunisian populations of dogs, different in
      breed and life style: 23 rural dogs and 26 dogs of European breeds. All were
      symptomatic and lived in the north of Tunisia where human visceral and cutaneous
      leishmaniasis caused by Leishmania infantum are endemic. Leishmaniasis has been
      confirmed in all dogs by serology or/and by parasitic identification. Significant
      differences concerning age and symptoms suggest a higher susceptibility to
      infection in European imported breeds. In fact individuals of this population
      were significantly younger; 81% were less than 5 years old whereas 57% of the
      autochthonous rural dogs were more than 5 years old with 31% of them being older
      than 9 (p = 0.014). In spite of their young age, 75% of imported breeds presented
      an affection of their general state with more frequent cutaneous symptoms than
      the rural dogs (96% versus 69%, p = 0.02). Isoenzyme typing of 31 strains,
      obtained from the two populations, from different sites (blood, lymph nodes,
      spleen) has only identified the zymodeme Leishmania infantum MON-1. This stresses
      the need of more investigations to determine reservoirs of the other enzymatic
      variants identified in humans in Tunisia and Mediterranean basin.

PMID- 16425714
TI  - [Lymphatic filariasis in Republic of Congo and scrotal elephantiasis].
AB  - Cases of scrotal elephantiasis operated in the Brazzaville' hospital are
      naturally imputed to Wuchereria bancrofti, in spite of the absence of
      parasitological proof. This is due to the fact that data's diffused by WHO which
      are widely included in the literature, unfortunately present this filariasis as
      being endemic in the Republic of Congo. But it is impossible to identify what
      works are at the origin of this assertion during the 30 last years. What is
      certain, it is that no case of lymphatic filariasis was found at the time of the
      field surveys carried out on filariasis both in the Congo and in Gabon, country
      also presented as an endemic territory, at the end of the Seventies and during
      the Eighties. These works were unfortunately published in French. Since this time
      no publication related a fieldwork or a conclusive clinical observation has
      confirmed the presence of Wuchereria bancrofti in these two countries of Central
      Africa.

PMID- 16425715
TI  - [Sickle-cell crisis in the child and teenager in Brazzaville, Congo. A
      retrospective study of 587 cases].
AB  - Using files related to children admitted at the Brazzaville teaching hospital
      (Congo) between May 1995 and May 2002, the authors have studied the part of
      sickle cell crisis (SCC) in the sickle cell disease, have assessed the
      epidemiological particularities, the relation between some clinical, biological
      factors as well as the severity of the disease. On the whole, 587 SCC have been
      observed in homozygous SS children aged 6 to 17. The distribution was as follows:
      painful osteo-articular crisis (58.6%), abdominal crisis (23.5%), acute chest
      syndrome (14%), neurological strokes (3.2%) and priapism (0.7%). The neurological
      strokes (75%) and the hand-foot syndrome (77.8%) were predominant in male. As
      regards the interaction age-localization of the crisis, the hand-foot syndrome
      mainly concerned children under five, long bones and rachis impairment those aged
      11 to 15; abdominal and neurological crisis were observed especially before the
      age of 10, the acute chest syndrome after 10 (68.3%). Malaria (48.9%) and
      bacterial or viral infections (24.5%) proved to be the triggering factors when
      these are identified (188 cases). SCC occurred in 67.5% of the cases during the
      hot and rainy seasons. Moreover the haemoglobin F rate above 10% was correlated
      with a low prevalence of SCC, in particular the potentially severe crisis,
      revealing at the same time its protective value. These results show that SCC, by
      their frequency and/or their severity constitute a major handicap when the vital
      prognosis is not involved. Rigorous health habits, appropriate vaccination
      programme, adequate malarial prophylaxis, optimal transfusional strategy and
      especially the use of hydroxyurea, prove to be urgent preventive measures to put
      into practice. Their efficient implementation will provide a better quality of
      life to the sickle cell patient and will decrease the risks of severe crisis.

PMID- 16425716
TI  - [Epidemiology, clinical features and prognosis of juvenile tetanus in Dakar,
      Senegal].
AB  - This study was conducted to determine the prevalence of juvenile tetanus and to
      describe its epidemiological aspects, clinical features and prognosis. We
      prospectively recruited tetanus cases among patients in the age group 1-15 years
      admitted to the Infectious Diseases Clinic in Fann teaching hospital, Dakar, from
      March to September 2002. Forty cases of juvenile tetanus were recruited,
      accounting for 5.3% of total patients and 43% of all tetanus cases hospitalized
      during the study period. Mean age was 8.8 years +/- 4.4 years and sex-ratio M/F
      was 3. None of the patients was reported to have completed a full course of
      tetanus toxoid and most of them (77%) had been living in suburbs in Dakar were
      uneducated (77%) and had parents with no occupation (70%). Portals of entry were:
      skin injuries (62%), circumcision (20%), ear pearcing (5%) and suppurative otitis
      (8%). Tetanus became widespread in all cases, most of which having mild grade
      disease (72%). Pseudomonas aeruginosa bacteremia was diagnosed in the development
      of two fatal cases of otogenous tetanus. The overall case fatality rate was 8%
      (three deaths) and no sequelae was observed among those who recovered. The
      expanded programme on immunization should be reinforced and complemented with
      booster doses strategy to avoid tetanus whatever the age group.

PMID- 16425717
TI  - [The cutaneous leishmaniasis of the face in Gafsa area, Tunisia].
AB  - The cutaneous leishmaniasis is a frequent affection in Tunisia. In the Gafsa
      region it is a endemoepidemic infection. Our prospective study was carried out on
      225 cases of cutaneous leishmaniasis of the face collected over two years in the
      outpatients' department of dermatology at Gafsa hospital. The aim of our study
      was to know more about the evolutive epidemio-clinical particularities of the
      cutaneous leishmaniasis of the face. The relative frequency of the cutaneous
      leishmaniasis of the face for the new patients reached 5%. An equal distribution
      between the two sexes was noted. The average age of our patients was 24 years old
      and 6 months old with extremes ranging from 3 months to 77 years. The nodular and
      ulcerated forms were the most frequent (35.3%), followed by impetiginoid forms
      (23%), then the lupoid forms (15%). The papular form was quite frequent (13%).
      Impetiginoid lesions occurred frequently in the child. Lupoid lesions appeared
      particularly on the nose. The complicated forms: the cutaneuos necrosis or
      erysipelas of the face appeared after intralesional injections of meglumine
      antimoniate (Glucantime). The intramuscular meglumine antimoniate was used in 172
      patients, among them 47 needed two treatments or more because of a particular
      resistance of the lesions of the face. The pimple of Gafsa, term initially used
      for ulcerated skin nodules, was actually characterised by a lesional
      polymorphism. The prognosis was good however the risk of in aesthetic scar of the
      face was important.

PMID- 16425718
TI  - [Penile sporotrichoid cutaneous leishmaniasis].
AB  - The localisation of the cutaneous leishmaniasis of L. major at the penis level is
      rare, we report here a new observation. Mr K. R aged of 41, without known
      pathological background presented for 20 days a nodular lesion of the anterior
      face of the neck, 2 juxtaposed ulcerated nodular lesions of the left wrist. He
      presented also subcutaneous nodules ranged linearly and extended to the root of
      the penis. Theses lesions were covered by an erythematous or ulcerated skin. The
      smear made from the genital lesions of the penis confirmed the diagnosis of a
      cutaneous leishmaniasis. The evolution was favourable after a 21 days treatment
      by doxycyclin after an interval of one week. Our observation was specific by the
      localisation of the cutaneous leishmaniasis and by the clinical form. This shows
      that in our region cutaneous leishmaniasis is characterised by different clinical
      symptoms.

PMID- 16425719
TI  - [Recombinant antibodies: a new application in scorpion envenomation?].
AB  - Serotherapy is the only specific treatment for envenomation. The antibodies are
      obtained after the purification of serum from hyperimmunised horses and are used
      after fragmentation in the form of polyclonal Fab or F(ab)'2. The anti-venom sera
      are heterogeneous, and their protective effect is often weak. The administration
      of these preparations induces risks of immediate or delayed side effects:
      hypersensitivity reactions, anaphylactic shock and serum sickness. This
      observation led us to develop new forms of antibodies produced by molecular
      engineering, capable of specifically neutralizing the neurotoxins responsible for
      the toxicity of the venom of Androctonus australis Hector. The recombinant
      antibody fragments are more homogeneous than conventional antivenoms and
      perfectly characterized in terms of specific activity. The method used to obtain
      them eliminates the risk of transmission by non-conventional transmissible
      agents. The earliest results confirm the importance of these new molecules (scFv
      recombinant Fab, diabody, triabody) and their ability to neutralize the action of
      scorpion neurotoxins. They could open the path to a new generation of more
      homogeneous antivenoms that are better tolerated and have well-characterized
      intrinsic properties.

PMID- 16425720
TI  - [Reasons for consulting related to skin-bleaching products used by 104 women in
      Brazzaville].
AB  - A prospective survey has been carried out in the Brazzaville (Congo) dermatology
      service in order to specify dermatosis linked to the use of bleaching agents in
      104 Congolese women consulting for this problem. The used bleaching agents were
      topical corticoids based products for 40 cases, hydroquinone for 32 cases, and
      hydroquinone associated with topical dermocorticoids for 32 cases. Acne was the
      most frequent motive for consulting (24%), followed by the paradoxical peri
      orbital hyperpigmentation (21.1%), profuse mycosis (16.3%) and vibices(8.6%). The
      results of this survey were not superimposable to those of Dakar where infectious
      dermatosis were the first reason for consulting.

PMID- 16425721
TI  - [Syphilis test proposed within the context of a programme to reduce mother/child
      HIV transmission: example of the Wassakara Health Care Center in Abidjan].
AB  - During the program MTCT+ set up in Abidjan by the national authorities with the
      assistance of the FSTI and FGSK, free screening and treatment of the syphilis
      infection were proposed to pregnant women. One test of agglutination on blades
      VDRL (Carbon Antigen Biotec the U.K.) and one TPHA test on plates for the
      positive VDRL (TPHA Nosticon Biomerieux F) were performed. Over the period from
      June 1999 to December 2001, 4 320 samples were taken. The laboratory observed 84
      positive tests VDRL and 59 confirmed by TPHA, that is to say a syphilis
      seroprevalence (TPHA) of 1.4%. In addition 391 results were not available for
      various reasons (errors of numbering, haemolysed blood, absence of reagents,
      etc.) ie. 9.0%. Among the 59 positive women (TPHA), 30 came back for their result
      and 23 women were correctly treated (3 or 4 penicillin delay injections). In
      addition 7 partners received a complete treatment and 8 incomplete treatment. The
      cost of each detected and treated case rose approximately to 150 Euros, which is
      relatively low except in time/ staff and indirect costs for women. This study
      confirmed that all the activities of SMI must be integrated to have an efficient
      PTME programme. The biological assessment must be accessible as a whole, to
      minimize the additional costs and transportations. A training of all the
      personnel in 2002 helped to improve in an important way the results of the
      intervention in the center.

PMID- 16425722
TI  - [Effects of age on causes of hospitalization in children suffering from sickle
      cell disease].
AB  - The objective of this work was to assess the frequency the nature of
      complications and prognosis of the disease in children suffering from sickle cell
      disease. This retrospective study was conducted from January 2002 to December
      2003 among 251 children suffering from sickle cell disease, hospitalized at the
      Brazzaville Teaching Hospital, Congo. The main hospitalization causes were
      dominated by the vaso-occlusive crisis (26.7%), anaemic crisis (20.3%) and
      infections (36.6%). The vaso-occlusive crisis were observed particularly in the 5
      year-old children (p < 0.05); the hand-foot syndrome concerned in particular
      children under 5 years old. Anaemic crisis were found almost exclusively in
      patients under 5 (p < 0.05). The infections in children under 5 (35.8%) were
      almost as frequent as in older children (37.4%). Some non infectious
      complications were only observed in children above 5: cholithiasis, 4 cases;
      heart failure, 4 cases; hip osteonecrosis, 1 case. Global mortality was 4.8% and
      higher in children under five (p > 0.05). In addition, the death causes were
      dominated by anaemic crisis. In conclusion, this study stresses on the need to
      implement a primary prevention as well as a secondary prevention adapted to age.

PMID- 16425723
TI  - [Body composition in Negro African children suffering from sickle cell disease. A
      mixed cross-sectional longitudinal study in Brazzaville, Congo].
AB  - This study evaluates the changes of body composition in homozygous children
      suffering from sickle cell disease and appreciates the interaction between some
      factors of severity of the disease. A mixed cross-sectional longitudinal study
      with control cases cohort was conducted in Brazzaville (Congo) among 91 children
      with sickle cell disease (45 boys and 46 girls) and 95 healthy children (48 boys
      and 47 girls), aged of 8-17 years old. Each group was initially divided into
      three subgroups of age: 8, 11, 14. These children were subsequently followed for
      3 years. Each year, at the same period, body mass, percentage of body fat, lean
      body mass and body mass index were evaluated in the two groups and then compared.
      The effects of frequency of painful episodes, the number of severe anaemia crisis
      and haemoglobin F on different variables were also appreciated. The children with
      sickle cell disease had stunting, lower values of body mass (p < 0.001),
      percentage of fat (p < 0.01), lean body mass (p < 0.01), and body mass index (p
      <0.001) between 8 and 17 years of age. In addition, we observed a non linear
      association between body mass index and fat percentage, but this interaction was
      stronger in girls. Finally the yearly frequency of painful episodes, the number
      of severe anaemia crisis and haemoglobin F had most of the time an influence on
      body composition. Children with sickle cell disease had a decreased body
      composition influenced by the complications associated with the disease . These
      limitations are modulated by haemoglobin F but the body composition is affected
      by painful episodes and severe anaemic crisis. Therefore more care and attention
      are recommended for the children suffering from sickle cell disease in order to
      control this severe disease.

PMID- 16425724
TI  - [Use of agricultural insecticides in Benin].
AB  - The use of insecticides in households and in agriculture has been incriminated in
      the emergence of insecticide resistance in insect vectors. For farming staff, the
      emergence of vector resistance is due to indoors spray of insecticides using
      aerosols and other low quality products in rural and urban settings against
      mosquitoes. On the other hand, public health specialists believe that the
      phenomenon of resistance could be due to massive use of insecticides in
      agriculture for field pests control. In Turkey, the implication of agricultural
      use of pesticides in the selection of vector resistance is clearly established.
      This study was framed to identify potential practices favouring the emergence of
      insecticide resistance in the Republic of Benin. Interviews and focus group
      discussions were organized with cotton, rice and vegetables farmers. The final
      aim of these surveys was to point out practices likely to favour the emergence of
      resistance. The research is conducted in 3 cotton fields, 2 rice fields and 2
      vegetable plantations. After filling and signing concerned forms, farmers are
      subjected to quantitative and qualitative questionnaires to generate data on:
      insecticides being used, the various doses applied for pests eradication, the
      frequency of treatments, the cost of treatments (cost/hectare/year) the origin of
      insecticides, the place of purchase, safety precautions and related health
      hazards. The results of this study have shown that the use of insecticides in
      agriculture is a clear fact. During treatments, insecticide residues get in
      contact with mosquito breeding sites where they diffuse into water and exercise a
      selection pressure on larvae. This partially explains the high levels of
      resistance recorded in with strains of Anopheles gambiae collected in
      agricultural settings under insecticides pressure. Pyrethroids and more
      specifically deltamethrin and cyfluthrin are the insecticides mainly used in
      studied localities. Bedrooms of farmers are used as storage place for half-used
      and un-used insecticides containers. For a proper management of insecticides,
      cotton and vegetable plantations farmers receive assistance from the ministry of
      rural development. Because of the importance of cotton production in the Republic
      of Benin, trainings on management of insecticides in agricultural settings are
      frequently organised by the ministry of rural development and are opened to
      farmers and their family members (husbands, wives, children and relatives...). In
      the long run, the whole family learns and becomes very versant with the use of
      insecticides, spraying frequencies, spraying devices and spraying techniques.

PMID- 16425725
TI  - [Susceptibility of Culex quinquefasciatus to insecticides in Bobo Dioulasso,
      Burkina Faso].
AB  - This study conducted from 1999 to 2000 in the suburbs of Bobo Dioulasso a town in
      the South of Burkina, aimed at investigating the susceptibility of the local
      population of Culex quinquefasciatus to various insecticides and proposing
      alternative strategies allowing a better management of insecticide resistance in
      the field. Eggs of C. quinquefasciatus were first collected in stagnant waste
      water places. The larvae were reared to early 4rth instar and tested by larval
      bioassays to determine the LC50/95 and the resistance ratios (RR50 and RR95) as
      well as their confidence intervals. A susceptible reference Strain "Slab" was
      used as control. Resistance was found to DDT and pyrethroids, but reduced
      susceptibility was found for carbamates, organophosphorates, phenyl pyrazole and
      in a less extend to Bacillus sphaericus. Resistance to pyrethroides is quite
      alarming since these insecticides are mainly used for bed net impregnation for
      the Roll Back malaria programme implemented in Africa. The high levels of
      insecticide resistance in C. quinquefasciatus suggest that alternative strategies
      have to be implemented to minimize the pressure of selection on resistant genes.
      The use of bio-larvicides (Bacillus sphaericus) alone or in rotation with
      different compounds may be a promising strategy for controlling C.
      quinquefasciatus in Bobo Dioulasso.

PMID- 16425726
TI  - [Phlebotomus (Larroussius) langeroni Nitzulescu, 1930 in Tunisia: presence of the
      female and updating of geographical distribution].
AB  - The authors report the presence of Phlebotomus (Larroussius) langeroni
      Nitzulescu, 1930 in two epidemic foci of cutaneous leishmaniasis due to
      Leishmania infantum in northwest Tunisia. The Phlebotomus langeroni female is to
      be mentioned for the first time in North Africa.

PMID- 16425728
TI  - [Transitional cell carcinoma involvement of the prostate].
AB  - Transitional cell carcinoma of the prostate (PTCC) has become a well recognized
      entity and is increasing in incidence due to the growing awareness of and search
      for. PTCC is part of the well known pan-urothelial disease: particularly the
      urologist must always consider the prostate in the management of superficial and
      invasive bladder cancer. Most cases are diagnosed in association with bladder
      cancer (secondary PTCC): primary prostatic transitional cell carcinoma arises "de
      novo" as the first tumor of the prostate urothelium and is rare. Prognosis
      depends on the prostate invasion degree. No reliable staging system is presently
      available. Non-invasive PTCC can be successfully treated with conservative means
      (TUR +/- BCG) whereas stromal invasive PTCC must be aggressively treated with
      radical cystectomy. PTCC can interphere with surgeon's decisions about urinary
      diversion in patients undergoing radical cystectomy for urothelial cancer.

PMID- 16425727
TI  - [Role of the combination of external radiotherapy--partial cystectomy-
      interstitial brachytherapy in pT1 G3, pT2 and pT3 bladder tumors].
AB  - Although it is still the reference method for curative treatment of invasive
      bladder cancer, radical cystectomy is a major surgical procedure justifying the
      evaluation of surgical tumoral excision in combination with curietherapy. At Nice
      University Hospital, between 1986 and 1998, 29 men with invasive bladder cancer
      were treated by partial cystectomy and interstitial brachytherapy. All the
      patients received external preoperative radiation of the pelvis of 10.5 Gy (Three
      3.5 Gy flashes) three days before partial cystectomy associated with implantation
      of curietherapy guides carried out on average Five days after surgery with the
      dose of 50 Gy. After between 5 to 17 years of follow-up, eight deaths out of 14
      occurred due to the disease and/or treatment, three patients had a superficial
      recurrence and one patient underwent salvage prostatocystectomy. Curietherapy
      gave rise to no direct complications, three patients suffered an eventration and
      1 evisceration. Two out of 15 surviving patients suffer from invalidating
      pollakiuria and one from chronic retention. This study shows that overall
      survival corrected for intercurrent deaths is lower than data in the literature,
      though the low sample size makes it impossible to compare the carcinological
      results and survival per pT category. In addition, this strategy results in fewer
      complications after radiation therapy. Hence, although a certain number of
      questions remain unanswered, it seems possible for suitably selected patients to
      expect the same cure rates as radical surgery with reduced morbidity.

PMID- 16425729
TI  - [What is the best bladder replacement].
AB  - Among the surgical options for bladder replacement proposed after cystectomy, the
      ileocaecal pouch system has been abandoned for twenty years because of its poor
      gastrointestinal tolerance. Colonic enterocystoplasty is useful because of the
      reduced risk of degeneration and fewer repercussions on gastrointestinal
      absorption. However, replacement with the ileum is today the reference
      cystoplasty with three main techniques: Hautmann bladder, Studer pouch and Foch Z
      shaped pouch. According to the data in the literature, these techniques offer
      similar overall performances and the results therefore remain mainly operator
      dependent. Efficacy in terms of urinary continence is optimized by the
      preparation of a detubularized neobladder with a "physiological" functional
      capacity, the preservation of the sphincter as well as perineal-abdominal re
      education which is started immediately after surgery. Direct ureteral
      reimplantation in the detubularized bladder is today an effective and sufficient
      technique to prevent vesico-renal reflux. Tumor recurrences do not seem be
      dependent on the type of ureteral reimplantation, nor on the type of initial
      bladder tumor. Extemporaneous examination of the cross-section of normal urethral
      section (no tumor, dysplasia, or carcinoma in situ) makes it possible to exclude
      the risk of urethral recurrence.

PMID- 16425730
TI  - [Laparoscopic promontofixation technique].
AB  - Laparoscopic promontofixation often remains possible whatever the previous
      history of pelvic surgery, including the placing of prosthetic material.
      Preoperative care is standardized and is accompanied by antibiotic prophylaxis,
      preventive antithrombotic treatment and in the event of a history of pelvic
      surgery, a digestive preparation. Positioning of the patient must plan a 30
      degrees Trendelenbourg position. After the introduction of trocars, initial
      surgery comprises interrectovaginal dissection to free the whole posterior
      surface of the vagina. This is followed by the installation of a posterior mesh
      pre-cut in an arch. The anterior face of the promontory is then freed after
      incision of the posterior peritoneum with the patient placed beforehand in a
      Trendelenbourg position. After intervesical vaginal dissection, the anterior
      prosthesis comprising a precut polyester mesh is fixed avoiding excess traction.
      The end of the surgery involves careful reperitonization of all the prosthetic
      parts. Possible specific surgical complications are vascular and visceral wounds.
      Postoperative secondary haemorrhage and gastrointestinal occlusion may occur.
      Occurrence of an inflammatory syndrome and low back pain suggests spondylodicitis
      and MRI should be performed. Vaginal erosion on the prosthesis (1.6 to 10%
      depending on the series) may occur after several months and seems relatively
      independent of the prosthetic material used.

PMID- 16425731
TI  - [Surgery for genitourinary prolapse: prosthesis or no prosthesis?].
AB  - In view of the limits of traditional surgery in the restoration of a normal
      vaginal anatomy and function in genitourinary prolapse, the use of either of
      synthetic, or more recently biological prosthetic materials, appears to be a
      necessity. Among synthetic materials, a macroporous net made of a wide mesh of
      knitted polypropylene monofilaments is currently the reference product for
      prosthetic surgery of urogenital prolapsus, laparoscopic promontofixation, but
      also, for the treatment of the cystoceles by the endovaginal route. Materials of
      human origin are apparently more flexible and the first results seem to show
      reduced erosion rate, but longer follow-up is required to specify their role in
      routine practice.

PMID- 16425732
TI  - [Genitourinary prolapse in daily practice: analysis of our bordelaise serie].

PMID- 16425733
TI  - [The UrEpik study: a descriptive epidemiological approach to lower urinary tract
      symptoms, sexual disorders and urinary continence in four countries].
AB  - UrEpik is a cross-sectional, epidemiological study undertaken in four cities
      (Auxerre, Birmingham, Nijmegen and Seoul) to determine the prevalence of lower
      urinary tract symptoms, urinary incontinence and erectile dysfunction in men aged
      from 40 to 80 years and their female partners, if applicable. Numerous evaluation
      questionnaires were collected by post, telephone or direct contact from 4876 men
      and 3657 women. The prevalence of lower urinary tract disorders was significantly
      different from one country to another, but increased constantly with age in
      particular in men with an I-PSS between 8 and 19 for whom it increased by
      approximately 10% per decade. Incontinence in men seems to be an important
      problem both in terms of discomfort score and wearing of protection and it
      increases with age. Analysis of erectile dysfunction (ED) gave different results
      depending on the method of investigation used. The SFI (sexual functional index)
      showed a positive correlation between ED and age, which was not found by direct
      questioning. The psychological impact of ED varied according to culture and age
      of the subject.

PMID- 16425734
TI  - [Can IPSS be modified or replaced to evaluate BPH in daily practice?].
AB  - Despite all the national and international recommendations, few doctors use IPSS
      to diagnose and monitor patients suffering from benign prostatic hypertrophy. The
      purpose of this article is to re-examine the Literature on the various methods
      that may improve evaluation of patients suffering from BPH ranging from a direct
      integration of the specific discomfort caused by each symptom to the use of
      visual analog scales (VAS). Concerning VAS, there seems to be a strong
      correlation between the IPSS score and the score by VAS for the evaluation of
      symptoms, discomfort and quality of life. The improvements in symptoms following
      medical treatment are shown in a parallel manner by the IPSS and VAS. Additional
      complementary studies on a broad population of patients are necessary before
      proposing this new tool for the diagnosis and follow-up of patients suffering
      from BPH.

PMID- 16425735
TI  - [Evalution of benign prostatic hyperplasia].
AB  - Benign prostatic hyperplasia is a disorder of aging men and according to reasons
      for consultation its incidence is continually increasing in parallel with the
      constant increase in life expectancy. Recommendations about its management have
      been made by numerous national and international, scientific authorities and
      those responsible for public health. However, despite a rationale based on
      regularly published data, there are many disparities between them and they are
      only partially followed up in routine practice. The purpose of a working group
      during the "2nd Interfaces in Urology" was to make a new assessment on this
      disorder with regard to the most recent data and existing recommendations, in
      order to offer clinicians a clearer attitude for the prescription of the initial
      evaluation of benign prostatic hyperplasia.

PMID- 16425736
TI  - [The new seniors. Sociological and medical aspects].
AB  - Medical progress has led to a spectacular increase in life expectancy. The world
      population is ageing in a context of rapid technological change destabilizing
      individuals and societies in their values and functions to such a point that it
      is Leading to a true change in civilization. Seniors have become important socio
      economic players with a feeling of prolonged youth and autonomy. Globalization
      has generated a feeling of insecurity and a constantly growing need for more
      information. In the face of these changes, adaptation in rhythm ranges, according
      to the individual, from reticence in its extreme form, the principle of
      precaution, through fatalistic passivity to opportunistic enthusiasm. In the
      medical field, patients have access to all modern means of information, and the
      most well-informed tend to behave more or less consciously as healthcare
      consumers, modifying the relationship with doctors which may become a service
      provider-client type relationship. A new relation to the body and with others has
      appeared with desires and also performance obligations. The difficulties of
      adaptation to this complex and socially anxiogenic world are expressed by
      permanent social conflicts and the increasing recourse to individual
      psychotherapeutic support.

PMID- 16425737
TI  - [Practice in private professional corporations].
AB  - Since 1992, doctors may exert through a private professional corporation. The
      Decree no 94-680 of 3rd of August 1994 details the new regulation. For physicians
      used to the liberal scene, one of the greatest innovation is the payment mode. It
      is basically divided in two parts: the work remuneration as wages or management
      allowance, and capital remuneration as dividends. This last possibility offering
      important savings on social contribution, social contribution being calculated
      only on the work remuneration part. Taxation being in this case a taxation of the
      company and of the physician on his incomes and dividends. It is a precious
      instrument to take part in a regrouping and to integrate new associates.
      Nevertheless it still is an individual's choice and before getting engaged,
      consequences of the choices selected have to be appreciated with a qualified
      professional.

PMID- 16425739
TI  - [Methodological analysis of an article].
AB  - Methodological analysis, in particular of an article on a clinical trial, first
      comprises a check of the quality of the study design: description of the primary
      objective and assumptions leading to the conduct of the study; description of
      patients; description and justification of the treatments compared and primary
      end-point; justification for the number of included patients; description of
      randomization; suitable statistical tests selected a priori; respect of legal and
      ethical framework. Then, in the results, the comparability of the randomly
      assigned groups must be checked. The primary end-point must be assessed by
      intention to treat analysis, then per protocol where necessary. Lastly, it is
      necessary to seek bias liable to reduce the quality of the demonstration.

PMID- 16425738
TI  - [Structure of a medical article].
AB  - The publication of medical research results requires that articles are drafted
      with a current well-codified structure that must be respected to convince the
      editorial board of a review and then its readers. The title must be short and
      relevant in order to best reflect the contents of the article and to allow its
      effective search on the Internet. The universally adopted structure is the IMRAD
      (Introduction Methods, Results and Discussion). The introduction is a
      prerequisite; it presents current knowledge on the problem studied, justifies the
      subject of the work and specifies its objective within this context. The
      "Methods" section describes the population, the type of study and its
      methodology, the equipment used, the primary and secondary end-points studied as
      well as the statistical methods used for analysis. The "Results" section
      describes the raw results associated with the statistical tests illustrated by
      relevant tables and figures. The "Discussion" section is used to underline
      results that are considered to be important and to compare them with those
      already published in the field. It may also contain comments on potential bias
      and suggest the impact of the results on daily practice and/or future research. A
      conclusion may finalize the discussion or form the subject matter for an
      independent section. Lastly, all articles include a relevant summary and a
      suitable bibliography.

PMID- 16425740
TI  - [Epidemiology of nephrolithiasis in France].
AB  - Nephrolithiasis is a frequent disease that affects about 10% of people in western
      countries. The prevalence of calcium oxalate stones has been constantly
      increasing during the past fifty years in France as well as in other
      industrialized countries. Stone composition varies depending to gender and age of
      patients and also underlines the role of other risk factors and associated
      pathologies such as body mass index and diabetes mellitus. The decrease in
      struvite frequency in female patients is the result of a significantly improved
      diagnostic and treatment of urinary tract infections by urea-splitting bacteria.
      In contrast, the increasing occurrence of weddellite calculi in stone forming
      women aged more than 50 years could be the consequence of post-menopausal
      therapy. A high prevalence of uric acid was found in overweight and obese stone
      formers and in diabetic ones as well. Another important finding was the increased
      occurrence with time of calcium oxalate stones formed from papillary Randall's
      plaques, especially in young patients. Nutritional risk factors for stone disease
      are well known: they include excessive consumption of animal proteins, sodium
      chloride and rapidly absorbed glucides, and insufficient dietary intake of fruits
      and potassium-rich vegetables, which provide an alkaline load. As a consequence,
      an excessive production of hydrogen ions may induce several urinary disorders
      including low urine pH, high urine calcium and uric acid excretion and low urine
      citrate excretion. Excess in calorie intake, high chocolate consumption inducing
      hyperoxaluria and low water intake are other factors, which favour excessive
      urine concentration of solutes. Restoring the dietary balance is the first advice
      to prevent stone recurrence. However, the striking increase of some types of
      calculi, such as calcium oxalate stones developed from Randall's plaque, should
      alert to peculiar lithogenetic risk factors and suggests that specific advices
      should be given to prevent stone formation.

PMID- 16425741
TI  - [Urinary parasitosis].
AB  - Parasites are rarely localized only in the urinary system. Schistosoma
      haematobium infection is very frequent in tropical Africa; it is revealed by a
      hematuria. Most hydatic cysts are localized in the liver, but a renal infection
      is possible. Other parasitoses (filariasis, malaria) often result in immune
      complex glomerulonephritis and are cured by specific treatment of the parasites.

PMID- 16425742
TI  - [Genital prolapse and colpocele. Coelioscopic sacrocolpopexy].
AB  - Genito-urinary prolapse is a common disease that requires a global approach which
      includes all the compartments. Sacrocolpopexy with anterior and posterior mesh
      allows long-lasting anatomical restoration with a preservation of the sexual
      function. The laparoscopic approach is a modern and efficient answer for this
      functional surgery.

PMID- 16425743
TI  - [Laparoscopic pyeloureteral anastomosis for ureteropelvic junction repair].
AB  - Pyeloureteral anastomosis is the most difficult act during Laparoscopic
      pyeloplasty. We report some technical aspects based on our experience and which
      may be useful to achieve such anastomosis in good conditions.

PMID- 16425744
TI  - 2006 preview: what's in store for the coming year?

PMID- 16425745
TI  - It is the worst possible time for cuts in the NHS.

PMID- 16425746
TI  - The future of nursing regulation.

PMID- 16425747
TI  - Listening to carers.

PMID- 16425748
TI  - Strategy and implications of managing long-term illness.
AB  - As the U.K. population is growing and living longer, inevitably there will be an
      increase in the number of people living with chronic illnesses. This article
      discusses the issues around managing chronic disease, highlighting current policy
      and implications for nurses and nursing practice.

PMID- 16425749
TI  - Parkinson's disease.

PMID- 16425750
TI  - The liver. Part 4: chronic liver disease.
AB  - Chronic liver disease and associated signs and symptoms present a challenge for
      clinical management as liver failure affects all body systems. While this part of
      the series concentrates on the physical symptoms of chronic liver disease, it
      needs to be remembered that these can also have many far-reaching implications
      for the patients' psychosocial well-being.

PMID- 16425751
TI  - The assessment and treatment of postnatal depression.
AB  - Postnatal depression is a common depressive illness with a variety of potential
      causes. This article outlines the detection of postnatal depression, the effects
      that the condition has on the whole family and treatment options.

PMID- 16425752
TI  - Improving patient nutrition through simple initiatives.
AB  - Nutrition is an important aspect of patient care and sometimes simple changes can
      make a significant difference. Initiatives such as Essence of Care and protected
      mealtimes can be used to improve patients' nutritional intake. While simple
      initiatives can often involve more work than expected, the final outcome and
      benefits for patients justify the time spent.

PMID- 16425753
TI  - Bupropion.

PMID- 16425754
TI  - The factors that affect HCA routes into nurse training.
AB  - AIM: A scoping study to give an insight into progression for health care
      assistants. METHOD: Semistructured telephone interviews were used to gain the
      views of strategic health authorities and workforce development directorates on
      HCA progression. These were compared with the Department of Health's figures on
      HCA progression. RESULTS: The main findings indicate that a new definition for
      the role of HCA is essential in order to monitor HCA progression. In addition,
      establishing more robust and transparent systems designed to support learning
      opportunities for HCAs is required, including accreditation of prior experiential
      learning systems. CONCLUSION: It appears there is inconsistency in practice
      across England and there are relatively few opportunities for HCA advancement.
      Recommendations for ways to support HCAs prior to devolving budgets and
      responsibility are offered.

PMID- 16425755
TI  - Making careers events work for you.

PMID- 16425756
TI  - A crucial part of the surgical team.

PMID- 16425757
TI  - It does not have to be right. It needs to act as a catalyst for a shift in
      thinking.

PMID- 16425758
TI  - Lobby for a smoking ban.

PMID- 16425759
TI  - 'Male patients get treated differently. Their views are never taken into
      consideration'.

PMID- 16425760
TI  - Is matron making it better?

PMID- 16425761
TI  - Star quality.
AB  - Many people will read their horoscopes as they look at the year ahead. But
      astrologists claim horoscopes can also give clues about illnesses to which you
      might be predisposed. They believe: Astrology can determine potential health
      problems as well as personality types. An accurate horoscope depends on good
      information about birth date and time. Anatomical regions correspond to
      astrological signs. Astrological signs are grouped into four function types.

PMID- 16425762
TI  - The right measure.
AB  - Obesity has been calculated traditionally by body mass index, but measuring waist
      circumference might be a more accurate way of identifying people at risk of
      cardiovascular disease. Excess visceral fat predisposes to several diseases,
      including diabetes and cardiovascular disease. The total cost to the NHS of
      obesity in 2001 was pounds sterling 2.5 billion. Waist circumference correlates
      well with visceral fat content.

PMID- 16425763
TI  - Model thinking.
AB  - Nancy Roper, Win Logan and Alison Tierney published their ground-breaking model
      of nursing in 1980, sparking the evolution of nursing theory from staid,
      biomedical thinking to an individualised, independent approach. Jane Salvage
      looks back at the lasting impact their research had on her and the profession as
      whole.

PMID- 16425764
TI  - Sex and dogma.

PMID- 16425765
TI  - Why size matters.

PMID- 16425766
TI  - Spot the difference.

PMID- 16425767
TI  - Where does this leave nursing?

PMID- 16425768
TI  - The importance of truth-telling in health care.
AB  - This article explores whether deception is ever justifiable in health care. It
      examines the concepts of truth-telling and deception. Possible reasons for the
      recent interest in truth-telling in health care are offered, including issues
      associated with deceiving patients. Wider arguments supporting and opposing
      deception in health care are considered before suggested alternatives to the use
      of deception in patient care are outlined.

PMID- 16425769
TI  - Nursing interventions for the management of patients with mania.
AB  - This article explores mania, a serious and often chronic illness that is mostly
      related to bipolar disorder but can present by itself or as a symptom of other
      illnesses. The signs and symptoms of the condition are examined and the nursing
      interventions reviewed.

PMID- 16425770
TI  - Involving and communicating with patients and the public.
AB  - Patient safety incidents have physical and emotional consequences for those
      involved, including patients, carers, relatives and healthcare staff. This
      article, the fifth of seven in this series, focuses on Step Five of the Seven
      Steps to Patient Safety (National Patient Safety Agency (NPSA) 2004): involve and
      communicate with patients and the public. The article discusses how to
      communicate with patients and their carers who have been involved in a patient
      safety incident that led to moderate harm, severe harm or death.

PMID- 16425772
TI  - Unconscious patients.

PMID- 16425771
TI  - Caring for the mechanically ventilated patient: part one.
AB  - This article examines the nursing care of mechanically ventilated patients in the
      intensive care unit. It focuses on the physiological changes and the clinical
      skills needed to assess and implement care for these patients. Part two, which
      will be published next week, examines weaning patients from mechanical
      ventilation.

PMID- 16425773
TI  - What I wish I had known then.

PMID- 16425774
TI  - Teaching journey.

PMID- 16425775
TI  - The way up.

PMID- 16425776
TI  - Vignette for community health nursing: advocacy for population health.

PMID- 16425777
TI  - JSU faculty and senior nursing students go to New Orleans.

PMID- 16425778
TI  - From technology stagnate to technology literate.

PMID- 16425779
TI  - Advanced practice nurses--who are they?

PMID- 16425781
TI  - Late bottle-weaning is associated with an increased risk of overweight.

PMID- 16425780
TI  - Healthcare issues--patient self determination acts and informed consent.

PMID- 16425782
TI  - Cultural competence--what it is, what it's not.

PMID- 16425783
TI  - Compassion fatigue--what is it, and how can you avoid it?

PMID- 16425784
TI  - Making sense of the "madness" of mercury: an Alabama perspective.

PMID- 16425785
TI  - [Comparison of power Doppler technique, microscopic examination and VEGF levels
      for the assessment of adrenal tumors vascularization].
AB  - The purpose of this study was to investigate the clinical usefulness of the color
      Doppler vascularity index (CDVI) in patients with adrenal masses before surgery.
      Twenty-four patients with adrenal masses were examined. The correlation between
      CDVI and microvessel density (MVD), vascular endothelial growth factor (VEGF)
      level and clinico-pathological factors was studied. There was a significant
      correlation between CDVI and VEGF level. The CDVI did not correlate with MVD. The
      CDVI was significantly higher in the patients with malignant or hormonally active
      tumors than in patients with benign non-hyperfunctioning lesions. Thus, the CDVI
      may be helpful in qualifying patients for adrenalectomy.

PMID- 16425786
TI  - [Permanent local nerve injuries after carotid endarterectomy].
AB  - Functional assessment of nerves, especially motor rami of cranial nerves, in
      patients at postoperative period after carotid endarterectomy (CEA), is
      particularly important in case of necessity of contralateral carotid artery
      surgery. Bilateral damage to recurrent laryngeal or hypoglossal nerve is a
      potentially life-threatening complication. Sensory disturbances due to
      intraoperative injuries of cervical plexus branches may cause residual discomfort
      in numerous patients. The aim of this study was the assessment and comparison of
      frequency of persistent (for more than 12 months postoperatively) manifestations
      of cranial and cervical nerves injuries in patients after CEA performed either in
      the standard or eversion technique. A prospective study evaluating cranial and
      cervical nerves dysfunction after carotid endarterectomies in 144 out of 193
      patients operated on from January 1999 until June 2001 was undertaken at the
      Department of General and Vascular Surgery, Pomeranian Medical University in
      Szczecin, Poland. CEA was performed in the standard way (i.e. by primary closure)
      in 92 patients, while 52 others were operated on by eversion technique.
      Neurological examination with careful functional assessment of cranial nerves: V,
      VII, IX, X, XII and cervical plexus, was performed according to a standard
      protocol within two follow-up periods: 3 to 6 and 12 to 18 months after discharge
      from the hospital. RESULTS: Dysfunction of recurrent laryngeal nerve and
      hypoglossal nerve were registered 12 to 18 months after CEA with similar
      incidence of 1.4%. There was no sign of residual damage to other cranial nerves.
      Sensory disturbances in the area supplied by cervical plexus, mainly transverse
      cervical and greater auricular nerve, were diagnosed in 26% of patients. There
      were no statistically significant differences in local neurological complication
      rates between patients operated on according to standard and eversion procedures.
      CONCLUSIONS: 1. Permanent damage of cranial nerves refers to small group of
      patients after carotid endarterectomy and concern predominantly recurrent
      laryngeal nerve and hypoglossal nerve. 2. Majority of local neurological
      complications are injuries to cervical plexus branches. 3. Eversion carotid
      endarterectomy is not related to higher incidence of local neurological deficits
      compared to standard procedure.

PMID- 16425787
TI  - [Concentration of glutathione (GSH), ascorbic acid (vitamin C) and substances
      reacting with thiobarbituric acid (TBA-rs) in single human brain metastases].
AB  - The aim of the study was to estimate the concentration of glutathione (GSH),
      ascorbic acid (vitamin C) and thiobarbituric acid (TBA-rs) in single human brain
      metastases and histologically unchanged nerve tissue. The research was conducted
      on fragments of neoplasmatic tissue collected from 45 patients undergoing surgery
      in the Department of Neurosurgery, Medical University of Bialystok in years 1996
      2002. Concentration of GSH was evaluated using the GSH-400 method, vitamin C
      using the method of Kyaw and TBA-rs using the method of Salaris and Babs. It has
      been found that there is a decrease of concentration of GSH and vitamin C and a
      considerable increase (p < 0.05) of concentration of TBA-rs in investigated
      single brain human metastasis in correlation to the concentration of the
      mentioned above substances in unchanged nerve tissue.

PMID- 16425788
TI  - [Low zinc and high copper levels in mothers of children with isolated cleft lip
      and palate].
AB  - Changes in orofacial development have been reported in offspring of animals
      treated with copper injections or low zinc diet during pregnancy. The aim of our
      study was to determine serum levels of zinc and copper in mothers of children
      with non-syndromic orofacial clefts and in women who gave birth to healthy
      children. Ninety six healthy women participated in the study: 35 mothers of
      children with cleft lip and cleft palate (CLP), 30 mothers of children with cleft
      palate (CP) and 31 control mothers of healthy children. Serum zinc and copper
      concentrations were determined by the use of inductively coupled plasma-mass
      spectrometry (ICP-MS). RESULTS: Between CLP and controls there were significant
      differences in mean zinc levels (511 +/- 121 microg/L vs 572 +/- 76 microg/L, p =
      0.012) and copper levels (991 +/- 388 microg/L vs 810 +/- 201 microg/L, p =
      0.02). In CP mean serum zinc and copper levels were 540 +/- 130 microg/L and 846
      +/- 291 microg/L. The ratio of serum zinc to copper levels was significantly
      lower in CLP comparing to CP and controls (0.57 +/- 0.19 vs 0.67 +/- 0.18 and
      0.74 +/- 0.19, p = 0.003). CONCLUSION: Our results suggest that trace elements
      may play a role in facial clefting in humans.

PMID- 16425790
TI  - [Own clinical experience in treatment of port-wine stain with KTP 532 nm laser].
AB  - Lesions of port-wine stain (PWS) type are the most commonly occurring vascular
      malformations of the skin which concerns about 0.3% of the population. These
      important from aesthetic and psychological points of view capillaries
      malformations have always been difficult for treatment. Previously applied
      methods consisting in cryosurgery, dermabrasion, radiation therapy or surgery and
      skin grafting produced unsatisfactory results. It was only when highly selective
      lasers were introduced that PWS could be treated effectively and safely. A lot of
      available lasers and lack of experience of the health care providers result in
      not always proper qualification of the lesions to the given laser type. The aim
      of the study was to present a prospective analysis of the efficacy of treatment
      of PWS vascular malformations by means of KTP 532 nm laser. From January 2003 to
      May 2005, 155 patients (115 women, 40 men) aged from 2 to 62 years (mean age
      18.23) were treated by means of laser at the Plastic Surgery Hospital in Polanica
      Zdroj, Poland. In the investigated population, the vascular malformation was a
      component of Sturge-Weber syndrome in 7 patients, Klippel-Trenaunay syndrome--in
      2 patients, while in one case it accompanied Recklinghausen disease. The vascular
      lesions had not been treated before in majority of cases, while in 37 patients
      the laser therapy was the continuation of other previously attempted treatment,
      which included excision and skin grafting, argon laser therapy, radiation therapy
      and pulsed dye laser treatment. The procedures were performed with at least 4
      week intervals without, or under local and in children general anaesthesia.
      Therapeutic efficacy was evaluated independently by 3 surgeons and a photographer
      on the basis of Subjective Scoring System (SSS) comparing simultaneously shown
      pictures of the patients taken prior to and after the last procedure. The
      outcomes of treatment were classified according to a 4-degree scale: excellent
      outcome--75-100% improvement, with 100% perceived as eradication of the lesion;
      good--50-74% improvement; fair--25-49% improvement and poor--less than 25%
      improvement, including no observable improvement. In 81% of the lesions (126
      patients) treatment with KTP 532 nm laser produced significant improvement which
      was found satisfactory by the patient. excellent outcome of treatment was
      obtained in 49 patients (31%), good in 42 (27%), fair in 35 (23%). However,
      despite many laser treatments using various energy and pulse duration, there was
      almost not observable improvement in 19% of the study population (29 patients).
      The PWS which failed to treatment were most commonly located on the limbs. The
      results of treatment was poor in 74% of malformations which were located beyond
      the face and neck (all of them were on the limbs). There was no episodes of
      scarring or persistent pigmentary changes in any of the patients. CONCLUSIONS: 1.
      KTP (532 nm) laser is an effective and safe tool in the management of capillary
      malformations of PWS type. 2. The treatment is especially effective in adults and
      in lesions localized to the face and neck area. 3. Port-wine stain localized on
      the trunk and extremities often appears to be KTP laser resistant.

PMID- 16425789
TI  - [Estimation of antioxidative effect of atorvastatin and fluvastatin used in
      primary prevention of coronary heart disease--effect on lipid peroxidation].
AB  - The study comprised 35 patients with mixed hyperlipidaemia and coronary heart
      disease (CHD) risk factors (overweight or obesity, low physical activity, family
      history). Seventeen patients were administered atorvastatin in a dose of 10 mg
      and 18 -fluvastatin in a dose of 40 mg once daily at bed time for 6 weeks. The
      control group consisted of 12 clinically healthy subjects with no CHD risk
      factors. Blood samples for testing were collected from cubital vein of patients
      after hypolipaemic diet prior to and 6 weeks after drugs application and once in
      control group. Malondialdehyde (MDA) concentrations in erythrocytes and plasma
      were determined by the method of Placer et al. MDA concentrations in erythrocytes
      and plasma were significantly higher (p < 0.05) in patients than in healthy
      subjects. After 6-week atorvastatin therapy MDA concentrations in erythrocytes
      and plasma decreased to the values observed in healthy subjects. In fluvastatin
      group erythrocyte and plasma MDA concentrations were unchanged and still
      significantly higher in comparison to the healthy subjects. Atorvastatin,
      contrary to fluvastatin, decreases lipid peroxidation in CHD risk patients.

PMID- 16425791
TI  - [Stroke mortality in Poland--role of observational studies based on computer
      databases].
AB  - Stroke is a leading cause of death worldwide and remains one of the major public
      health problems. Most European countries have experienced declines in stroke
      mortality in contrast to central and eastern European countries including Poland.
      The World Health Organization Data Bank is an invaluable source of information
      especially for mortality trends. Stroke mortality in Poland and some problems
      with accuracy of ICD coding for the identification of patients with acute stroke
      are discussed. Computerized databases are increasingly being used to identify
      patients with acute stroke for epidemiological, quality of care, and cost
      studies. More accurate methods of collecting and analysis of the data should be
      implemented to gain more information from these bases.

PMID- 16425792
TI  - [Evaluation of invasive tests in diagnosis of Helicobacter pylori infection and
      their correlation with endoscopic features in children with chronic gastritis].
AB  - Fifty children aged 8-17 years with histologically confirmed chronic gastritis
      were investigated for Helicobacter pylori (H. pylori) presence in gastric mucosa
      bioptates taken during endoscopy. Three invasive tests (histology, rapid urease
      test and culture) were done. H. pylori was stated in 26 patients (56%). In this
      group the positive results were as follows: histology--96.4%, urease test--82.1%,
      culture--60.7%. The consistency of positive results ranged from 60.7% to 78.6%,
      being most often for histology and urease test. In 91% of non-infected patients
      the endoscopic features were limited to erythematous, oedematous and exsudative
      changes of gastric mucosa, whereas in patients with H. pylori infection the
      prevalence of antral nodularity was noted in 60.7%. The probable causes of non
      compatible test results are discussed.

PMID- 16425793
TI  - [Role of the physician in recognition of causes and circumstances of alcohol
      abuse by patients in general rural dispensaries. Characterization of resources,
      staff and patients in the primary health care in the Lublin, Chelm, Zamosc and
      Siedlce voivodship (part I)].
AB  - As follows from the studies of patients of rural dispensaries, their socio
      demographic environment does not differ from that of commune health centers. The
      alcohol abusing patient is usually a man, 35-40 aged, married, not educated,
      farmer of low living standard. In both institutions of health care physicians are
      not well prepared for care of alcohol abusing patients whereby the number of
      properly trained physicians in rural dispensaries is twice as small as in commune
      health centers. The physicians in both institutions manage to recognize only a
      small percentage of alcohol abusers and usually those in advanced stage. The
      proper training of physicians as far as recognition, prophylaxis, solving alcohol
      problems, individual and group psychotherapy are concerned in essential in order
      to improve the existing situation.

PMID- 16425794
TI  - [Metalloproteinases activity (MMP-2, MMP-9) in distal stumps of rat sciatic
      nerves].
AB  - In case of nerve transection we observed biochemical and morphological changes in
      axons. The aim of present study was to examine neurotrophic activity of two
      important metalloproteinases: MMP-2 and MMP-9. To examine their activity in nerve
      supernatants, gelatin zymography was used. We concluded that the levels of MMP-2
      and MMP-9 expression are increased in 4th, 5th and 6th day after nerve
      transection. The identification of the molecular mechanism underlying this
      activity could be the main key for the elaborating of further strategies for
      repair of the damaged nervous system.

PMID- 16425795
TI  - [Cognitive impairment after coronary artery bypass grafting surgery].
AB  - Improvement of cardiosurgery treatment and perioperative care of CABG (coronary
      artery bypass grafting) patients has been associated with essential reduction of
      early mortality. Nevertheless neurological complications have not changed.
      Cerebrovascular death, stroke, encephalopathy and cognitive decline remain the
      most common disturbances. Cognitive impairment after CABG seems to be a
      multifactorial problem. Demographic, medical history and perioperative factors
      strongly influence cognitive outcome. Incidence of decline is common immediately
      after surgery (53-79%), less frequent after 6 months (10-30%) and it depends on
      cardiosurgery method (on-pump > off-pump surgery). Early impairment is the
      predictor of late cognitive deficit in the 5-year follow-up. Microembolic
      signals, cerbral hypoperfusion and systemic inflammatory response are the main
      reasons of damage. Neuropsychological tests consist of verbal and non-verbal
      memory, visuo-spatial and construction abilities, motor speed, language and
      executive functions evaluation. It is proposed to perform examinations before the
      operation and at least 3 months after CABG Twenty per cets or 1 SD decline in at
      least 20% of tests will be significant. Anxiety and depression signs should be
      taken into consideration as well.

PMID- 16425796
TI  - [Nitric oxide--doctor or killer?].
AB  - This study shows present knowledge on the role of nitric oxide (NO)--a reactive
      gas that functions both as a signaling molecule in endothelial cells and nerve
      cells and as a killer molecule. The article also presents how we can use NO in
      treatment.

PMID- 16425797
TI  - [Pathogenesis and treatment of acute coronary syndromes].
AB  - Acute coronary syndromes (ACS) include unstable angina and non-ST elevation
      myocardial infarction (UA/NSTEMI) and ST-segment elevation myocardial infarction
      (STEMI). Acute coronary syndromes lead to important epidemiological and
      economical problems. In polish population an estimated incidence of ACS is 250
      000 cases per year. 30-day mortality in UA/NSTEMI is approximately 3.5%, and 8.4%
      in STEMI. The atherosclerotic plaque instability with subsequent rupture and
      thrombus formation is a primary mechanism of ACS. Plaque destabilization is
      evoked by local and systemic inflammation. The primary risk factors in ACS are:
      age > 65 years, diabetes, peripheral artery disease, stroke, previous myocardial
      infarction and elevated levels of cardiac troponins. The guidelines for treatment
      of ACS are based on the results of large randomized clinical trials assessing the
      reduction of relevant clinical end-points (death, AMI, recurrent ischaemia). The
      goal of treatment of UA/NSTEMI is the stabilization of the plaque, prevention and
      reduction of myocardial ischaemia and AMI. Inefficient medical treatment and
      sustained symptoms are the indication for coronary angiography and percutaneous
      coronary intervention (PCI). The main goal of treatment in STEMI is quick
      regaining of the culprit vessel patency and maintaining of sufficient myocardial
      perfusion. It can be done by thrombolytic therapy or primary coronary
      angioplasty. In comparison to fibrynolysis PCI confers the lower risk of death
      and recurrent AMI. New regimens of pharmacological treatment (facilitated PCI)
      including the half-dose of fibrynolytic and GPIIbIIIa inhibitor prior to PCI are
      assessed to improve the efficiency of PCI.

PMID- 16425798
TI  - [Changes in central nervous system during preeclampsia].
AB  - Hypertension, proteinuria and edema, a syndrome called as EPH gestosis or
      preeclampsia is one of the most common causes of mortality of pregnant women and
      fetus. The etiology of the disease is not fully understood, the genetic factors
      are thought to play the main role. Changes in the central nervous system are
      dangerous complications of the gestosis which could cause convulsive eclampsia
      and stroke. The neuroimaging techniques, the neurophysiological and
      ultrasonographic investigations allow to diagnose the neurological complications
      of gestosis and to begin the treatment (symptomatic, because of unknown etiology)
      at right time. Then the cooperation of neurologists and obstetrician may prevent
      a lot of complications during pregnancy and delivery.

PMID- 16425799
TI  - [Transplantation of islets of langerhans--alternative or solution in type 1
      diabetes treatment?].
AB  - Diabetes mellitus is severe disease caused by partial or total lack of insulin
      leading to microangiopathy. Methods of treatment used today do not protect
      patients from the complications of disease. The proposed alternative of the
      treatment is transplantation of the pancreas islets. Till June 2003, 705
      transplantation were performed worldwide. Allotransplant trials were described so
      far, while xenotransplants may appear as an alternative using alien species
      donors. Immune incompatibility of a human and animals is a major problem in the
      method, which can be solved by the use of genetically modified animals. In vitro
      genetic modifications of the pancreatic islets were already undertaken. New
      perspective arose with the development of the "stem cells" technology-
      differentiation of the primary cells into the Langerhans islets cells.
      Contemporary data show positive value of the method and give new perspective in
      the treatment of diabetes mellitus with respect to its rising morbidity.

PMID- 16425800
TI  - [Selected aspects relative to somatoform disorders].
AB  - This article addresses somatoform disorders, which remain a challenging problem
      in contemporary psychiatry. Inadequate responses to stressors play a significant
      role in their development. The term "somatoform disorders" refers to illnesses
      that were previously termed "psychosomatic". This article defines disorders
      according to the ICD-10 classification while highlighting important differences
      between this and the DSM-IV classification. The article reviews expert opinions
      concerning somatoform disorders, particularly in regard to somatization,
      hypochondriasis and autonomic dysfunction in these conditions. Attention is drawn
      to the relationship between somatoform disorders and other psychiatric conditions
      including depression, anxiety disorders and personality disorders as well as to
      actual non-psychiatric illnesses. The influence of cultural background, sex and
      age is discussed. Difficult clinical conditions such as fibromyalgia and
      Munchhausen syndrome are also considered.

PMID- 16425801
TI  - [Hypersensitivity to poppy seeds].
AB  - Hypersensitivity to poppy seeds is rare and it may develop due to immune
      (allergy) and non-immune reactions of fulminant course. Two cases of
      hypersensitivity to poppy seeds are presented: in a 21-year-old woman and 32-year
      old man in whom life-threatening symptoms and signs of anaphylaxis (SSA)
      developed after consumption of poppy seeds in various situations, e.g in the
      street after consumption of a roll with poppy seeds or a cake prepared on a
      moulding board on which poppy seeds were previously squeezed. In the case of the
      woman, history data pointed to familial and individual occurrence of atopy, and
      positive cutaneous prick tests with allergens of grass/crop and weed pollen and
      tree pollen (birch, hazel) as well as hazelnuts. In the man the anamnesis and
      skin prick tests were negative. Serum concentrations of allergen-specific IgE
      (asIgE) for poppy seeds and, additionally, for food allergens, which, according
      to patients, also could be the cause of SSA: celery, pineapple, mixture of spices
      and nuts were determined. In the woman elevated concentrations of asIgE for
      celery (class 2) and nut mixture (class 2) with negative result for poppy were
      noted, whereas in the man elevated concentrations of asIgE for poppy (class 2)
      and nut mixture (class 2) were found. Additionally, in the male patient skin
      tests were performed with topical anesthetics and narcotic analgesics derived
      from poppy (morphine, codeine) finding positive reactions to xylocaine and
      codeine. CONCLUSIONS: The two presented cases illustrate that hypersensitivity to
      poppy seeds may occur in IgE-dependent or non-immune mechanisms and the presence
      of atopy is not decisive of its mechanism.

PMID- 16425802
TI  - [Difficulties in diagnosis of ruptured popliteal artery aneurysm].
AB  - Rupture is a very rare complication of popliteal artery aneurysm. In this paper a
      case of, originally misdiagnosed as an abscess, ruptured popliteal aneurysm in a
      82-year-old man is presented. Main symptoms were pain and a mass in distal part
      of the thigh and in popliteal fossa and anaemia. After admission to our
      institution arteriography was performed and the patient was operated on as an
      emergency. The part of destroyed popliteal artery was reconstructed with the
      segment of autogenous great saphenous vein.

PMID- 16425803
TI  - [Osseous metaplasia in rectal cancer in a 69-year-old man].
AB  - The first case of osseous metaplasia in rectal cancer is described. The authors
      present the diagnostic evaluation based on the transrectal ultrasound
      examination, determination of neoplastic markers, pathological examination,
      treatment, and follow-up in a 69-year-old man.

PMID- 16425804
TI  - [Calcifying epithelial odontogenic tumor (Pindborg tumor)].
AB  - The calcifying epithelial odontogenic tumor (CEOT) is a rare benign odontogenic
      neoplasm which was first described by Pindborg in 1955 representing only 1% of
      all odontogenic tumors. The tumor has an ectodermal odontogenic origin. This
      tumor are considered benign but can be locally aggressive in nature with
      recurrence rates of 10-15% reported. Surgical treatment varies from simply
      enucleation to partial resection of the affected bone. Since 1973 three cases
      only of the Pinborg tumor have been presented in the Polish literature. We
      described the case of a 44-year-old man with Pindborg tumor in the right maxilla.
      Standard x-ray examinations and CT scan were performed in order to obtain
      information about tumor's localization. Autors discuss the radiologic features of
      calcifying epithelial odontogenic tumor and treatment method and the relevant
      literature.

PMID- 16425805
TI  - [Mediastinal tumor as a cause of fetal hydrops].
AB  - Unusual case of fetal hydrops was presented. In a stillborn infant an Rh
      incompatibility was suspected as a cause of hydrops, although prentally an
      immunologic source of the illness was excluded. Post-mortem a large polycystic
      mediastinal teratoma with cardiac and pulmonary hypoplasia was stated as a main
      cause of the hydrops. Additionally, histopathological examination proved this
      diagnosis. The mediastinal tissue contained immature epithelial, mesenchymal and
      blastemal elements. The congenital teratomas should be taken for account in
      problematic diagnosis of complicated cases.

PMID- 16425806
TI  - Evidence-based practice.

PMID- 16425807
TI  - The American Nurses Association designates nephrology nursing as a recognized
      nursing specialty!

PMID- 16425808
TI  - Developing clinical protocols for nursing practice: improving nephrology care for
      children and their families.
AB  - Improving and maintaining quality patient care through the development and
      implementation of clinical protocols is an important facet in our health care
      system. Identifying the need for clinical protocols, developing and maintaining
      the protocols, and defining the specific role of pediatric nephrology nurses in
      this process is presented herein. To illustrate the process we have included two
      examples of current clinical protocols utilized by our division.

PMID- 16425809
TI  - Improving arteriovenous fistula cannulation skills.
AB  - Cannulation of arteriovenous fistulae is technically more challenging than
      cannulation of arteriovenous grafts. With the advent of the National Vascular
      Improvement Initiative, Fistula First, the United States has seen an increase in
      the number of arteriovenous fistulae. The problem we now face is how to refocus
      and reeducate nurses to the intricacies of arteriovenous fistula cannulation.
      Through evidenced-based practice and current best-demonstrated practices, this
      article will provide the tools needed to improve arteriovenous fistulae
      cannulation skills.

PMID- 16425810
TI  - Caregiving by family and friends of adults receiving dialysis.
AB  - This study examined the activities of caregivers of adults on dialysis and
      explored how these behaviors evolved over time. Using a grounded theory
      methodology, interviews were conducted with 37 caregivers. Caregivers shared a
      rich repertoire of caregiving abilities and activities that were often supported
      by a strong knowledge base. Caregiving activities fell into in five
      interdependent dimensions: appraising, advocating, juggling, routinizing, and
      coaching. Caregivers also described specific caregiving tasks, including dialysis
      related activities, management of diet, medications and symptoms, and personal
      care. These findings have important implications for nephrology nurses in
      planning care that acknowledges and supports the contributions of "lay"
      caregivers.

PMID- 16425811
TI  - Effective and safe IV iron and anemia management during home hemodialysis: a
      dialysis facility's experience.
AB  - Studies have shown that IV iron therapy, in conjunction with EPO, is essential in
      managing anemia in patients on hemodialysis. In addition, data have shown that IV
      iron therapy can be safely administered during hemodialysis, whether performed at
      home or in the center. Nurses should be aware of how to administer this therapy
      and be knowledgable of possible allergic-type reactions that have been associated
      with its clinical use.

PMID- 16425812
TI  - Nurses' impact on the choice and longevity of vascular access.
AB  - A preponderance of data highlights significant improvements in outcomes when
      patients dialyze with arteriovenous fistulae compared with either catheters or
      grafts. "Fistula First" is a nationwide, evidence-based, quality improvement
      effort that is striving to improve vascular access outcomes by increasing the
      percentage of patients who dialyze with arteriovenous fistulae. Nephrology nurses
      will have a profound effect on achieving the goals outlined by Fistula First,
      including both the choice and longevity of vascular accesses.

PMID- 16425813
TI  - Training a patient with visual impairment on continuous ambulatory peritoneal
      dialysis.

PMID- 16425814
TI  - Disaster preparedness for dialysis facilities.

PMID- 16425815
TI  - Should tunneled hemodialysis catheters really be permanent? Use of tunneled
      catheters must be minimized.

PMID- 16425816
TI  - Should tunneled hemodialysis catheters really be permanent? Bottom line: the
      decision belongs to the patient.

PMID- 16425817
TI  - Oxidative stress in chronic kidney disease.

PMID- 16425818
TI  - "Fistula First" as a CMS breakthrough initiative: improving vascular access
      through collaboration.
AB  - The arteriovenous fistula is the "gold standard" for ESRD vascular access, and,
      after the initial success of the ESRD Network national vascular access
      improvement initiative, CMS adopted "Fistula First" as a formal CMS Breakthrough
      Initiative. A formal coalition has been formed from members of the renal
      stakeholder community, and five task force groups are currently addressing
      various issues and aspects of the health care system surrounding successful
      arteriovenous fistula placement.

PMID- 16425819
TI  - The vascular access coordinator role: an interview with Donna Carlton by Betsy
      King.
AB  - In summary, the access coordinator is at the center of our access program at UAB.
      The coordinators can make decisions based on the calls we receive from the
      nursing staff and reports obtained from procedures. The ability to relay
      information to the entire team rather than simply data entry staff, makes us a
      central focal area for our access team. This type of model is working to help us
      achieve better patient outcomes. We provide many services but the most important
      is follow-up. As a result, we are able to achieve optimal outcomes for our
      patients.

PMID- 16425823
TI  - Directed donation: what is a transplant center to do?

PMID- 16425824
TI  - Design and quantitative evaluation of a stance-phase controlled prosthetic knee
      joint for children.
AB  - The aims of this study were to demonstrate a theoretical basis for the design of
      a stance-phase controlled paediatric prosthetic knee joint, clinically test
      prototypes of the knee, and use a questionnaire to evaluate its efficacy.
      Biomechanical models were used to analyze the stance-phase control
      characteristics of the proposed knee, and those of three other commonly
      prescribed paediatric knee joint mechanisms, which were also the conventional
      knee joints used by the six participants of this study (mean age 10.8 years). A
      questionnaire pertaining to stance-phase control was designed and administered
      twice to each child; once for the evaluation of the prototype knee joint and once
      for the conventional knee joint. Stance-phase modeling results indicated
      decreased zones of instability for the new knee as compared to other paediatric
      knee joints. Questionnaire results revealed a decrease in the frequency of falls
      with the prototype compared to other knees, especially in highly active children.
      The children also reported worrying less about the knee collapsing during
      walking. No differences were evident for stance-phase stability during running,
      walking on uneven terrain, ambulating up and down stairs and inclines, fatigue,
      and types of activities performed.

PMID- 16425825
TI  - A comparison of models of force production during stimulated isometric ankle
      dorsiflexion in humans.
AB  - In this paper, we compare seven models on their ability to fit isometric muscle
      force. We stimulated the ankle dorsiflexors of eight subjects at seven ankle
      angles (85 degrees-120 degrees). Three different stimulation patterns (twitch,
      triangular, and random) were applied at all ankle angles. Four additional
      patterns (doublets, steady rates, "catch property," and walking-like) were
      applied at 95 degrees. Parameter values were optimized for each model at each
      angle. Parameters for the general linear model were calculated using a novel
      least-squares algorithm. A linear, second-order critically damped model gave the
      poorest fits (average root mean square (rms) error: 15 N). The models of Ding et
      al. (2002) and Bobet and Stein (1998) gave the best fits (average rms errors: 9.2
      and 9.4 N). The other models (general linear second-order model, Wiener model,
      Zhou et al. (1995) model, general linear model) gave intermediate results.
      Results were similar at all ankle angles. We conclude that the Ding and Bobet
      Stein models are the best overall for isometric contractions, that no linear
      model of any kind will give an error less than 9% of maximum force, and that the
      models tested are consistent across lengths.

PMID- 16425826
TI  - School-based use of a robotic arm system by children with disabilities.
AB  - A robotic arm system was developed for use by children who had very severe motor
      disabilities and varying levels of cognitive and language skills. The children
      used the robot in a three-task sequence routine to dig objects from a tub of dry
      macaroni. The robotic system was used in the child's school for 12-15 sessions
      over a period of four weeks. Goal attainment scaling indicated improvement in all
      children in operational competence of the robot, and varying levels of gain in
      functional skill development with the robot and in carryover to the classroom
      from the robot experiments. Teacher interviews revealed gains in classroom
      participation, expressive language (vocalizations, symbolic communication), and a
      high degree of interest by the children in the robot tasks. The teachers also
      recommended that the robot should have more color, contrast and character, as
      well as generating sounds and/or music for student cues. They also felt that the
      robotic system accuracy should be increased so that teacher assistance is not
      necessary to complete the task.

PMID- 16425827
TI  - A time-series prediction approach for feature extraction in a brain-computer
      interface.
AB  - This paper presents a feature extraction procedure (FEP) for a brain-computer
      interface (BCI) application where features are extracted from the
      electroencephalogram (EEG) recorded from subjects performing right and left motor
      imagery. Two neural networks (NNs) are trained to perform one-step-ahead
      predictions for the EEG time-series data, where one NN is trained on right motor
      imagery and the other on left motor imagery. Features are derived from the power
      (mean squared) of the prediction error or the power of the predicted signals. All
      features are calculated from a window through which all predicted signals pass.
      Separability of features is achieved due to the morphological differences of the
      EEG signals and each NNs specialization to the type of data on which it is
      trained. Linear discriminant analysis (LDA) is used for classification. This FEP
      is tested on three subjects off-line and classification accuracy (CA) rates range
      between 88% and 98%. The approach compares favorably to a well-known adaptive
      autoregressive (AAR) FEP and also a linear AAR model based prediction approach.

PMID- 16425829
TI  - An apparatus for characterization and control of isolated muscle.
AB  - An apparatus for characterization and control of muscle tissue is presented. The
      apparatus is capable of providing generalized mechanical boundary conditions to
      muscle tissue, as well as implementing real-time feedback control via electrical
      stimulation. The system is intended to serve as an experimental platform for
      implementing a wide variety of muscle control and identification studies that
      will serve as fundamental investigations of muscle mechanics, energetics,
      functional electrical stimulation, and fatigue. In one illustration of the
      capabilities of the apparatus, pilot experimental results of muscle workloops
      against a finite-admittance passive load are presented, illustrating how richer
      boundary conditions may reveal interesting muscle behavior.

PMID- 16425828
TI  - Direct neural sensory feedback and control of a prosthetic arm.
AB  - Evidence indicates that user acceptance of modern artificial limbs by amputees
      would be significantly enhanced by a system that provides appropriate, graded,
      distally referred sensations of touch and joint movement, and that the
      functionality of limb prostheses would be improved by a more natural control
      mechanism. We have recently demonstrated that it is possible to implant
      electrodes within individual fascicles of peripheral nerve stumps in amputees,
      that stimulation through these electrodes can produce graded, discrete sensations
      of touch or movement referred to the amputee's phantom hand, and that recordings
      of motor neuron activity associated with attempted movements of the phantom limb
      through these electrodes can be used as graded control signals. We report here
      that this approach allows amputees to both judge and set grip force and joint
      position in an artificial arm, in the absence of visual input, thus providing a
      substrate for better integration of the artificial limb into the amputee's body
      image. We believe this to be the first demonstration of direct neural feedback
      from and direct neural control of an artificial arm in amputees.

PMID- 16425830
TI  - Automatic determination of synergies by radial basis function artificial neural
      networks for the control of a neural prosthesis.
AB  - This paper describes an automatic method for synthesizing the control for a
      neural prosthesis (NP) that could augment elbow flexion/extension and forearm
      pronation/supination in persons with hemiplegia. The basis for the control was a
      synergistic model of reaching and grasping that uses temporal and spatial
      synergies between the arm and body segments. The synergies were determined from
      the movement data measured in nondisabled persons during the performance of
      functional tasks. The work space was divided into six zones: distance (two
      attributes) and laterality (three attributes). Radial basis function artificial
      neural networks (RBF ANN) were used to determine synergies. Sets of RBF ANN
      characterized with good generalization were selected as control laws for elbow
      flexion/extension and forearm pronation/supination. The validation was performed
      for three categories: inter-subject, distance, and laterality generalization. For
      all of the defined spatial synergies, the correlation was high for inter-subject
      and distance, yet low for the laterality scenario. This suggests the necessity
      for implementing different maps for different directions, but the same maps for
      different distances. The natural movements of the upper arm then drive the lower
      arm (elbow flexion/extension and forearm pronation/supination) in a way that is
      very well suited for the administration of functional electrical therapy (FET) in
      persons with hemiplegia soon after the onset of impairment.

PMID- 16425831
TI  - Optimal arrangement of magnetic coils for functional magnetic stimulation of the
      inspiratory muscles in dogs.
AB  - In an attempt to maximize inspiratory pressure and volume, the optimal position
      of a single or of dual magnetic coils during functional magnetic stimulation
      (FMS) of the inspiratory muscles was evaluated in twenty-three dogs. Unilateral
      phrenic magnetic stimulation (UPMS) or bilateral phrenic magnetic stimulation
      (BPMS), posterior cervical magnetic stimulation (PCMS), anterior cervical
      magnetic stimulation (ACMS) as well as a combination of PCMS and ACMS were
      performed. Trans-diaphragmatic pressure (Pdi), flow, and lung volume changes with
      an open airway were measured. Transdiaphragmatic pressure was also measured with
      an occluded airway. Changes in inspiratory parameters during FMS were compared
      with 1) electrical stimulation of surgically exposed bilateral phrenic nerves
      (BPES) and 2) ventral root electrical stimulation at C5-C7 (VRES C5-C7). Relative
      to the Pdi generated by BPES of 36.3 +/- 4.5 cm H2O (Mean +/- SEM), occluded
      Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and a combined PCMS + ACMS were 51.7%,
      61.5%, 22.4%, 100.3%, and 104.5% of the maximal Pdi, respectively. Pdi(s)
      produced by UPMS, BPMS, PCMS, ACMS, and combined ACMS + PCMS were 38.0%, 45.2%,
      16.5%, 73.8%, and 76.8%, respectively, of the Pdi induced by VRES (C5-C7) (48.0
      +/- 3.9 cm H2O). The maximal Pdi(s) generated during ACMS and combined PCMS +
      ACMS were higher than the maximal Pdi(s) generated during UPMS, BPMS, or PCMS (p
      < 0.05). ACMS alone induced 129.8% of the inspiratory flow (73.0 +/- 9.4 L/ min)
      and 77.5% of the volume (626 +/- 556 ml) induced by BPES. ACMS and combined PCMS
      + ACMS produce a greater inspiratory pressure than UPMS, BPMS or PCMS. ACMS can
      be used to generate sufficient inspiratory pressure, flow, and volume for
      activation of the inspiratory muscles.

PMID- 16425832
TI  - A robotic device for studying rodent locomotion after spinal cord injury.
AB  - We have developed a robotic device (the "rat stepper") for evaluating and
      training locomotor function of spinal cord injured rodents. This paper provides a
      detailed description of the device design and a characterization of its robotic
      performance capabilities.

PMID- 16425833
TI  - An android for enhancing social skills and emotion recognition in people with
      autism.
AB  - It is well documented that the processing of social and emotional information is
      impaired in people with autism. Recent studies have shown that individuals,
      particularly those with high functioning autism, can learn to cope with common
      social situations if they are made to enact possible scenarios they may encounter
      in real life during therapy. The main aim of this work is to describe an
      interactive life-like facial display (FACE) and a supporting therapeutic protocol
      that will enable us to verify if the system can help children with autism to
      learn, identify, interpret, and use emotional information and extend these skills
      in a socially appropriate, flexible, and adaptive context. The therapeutic setup
      consists of a specially equipped room in which the subject, under the supervision
      of a therapist, can interact with FACE. The android display and associated
      control system has automatic facial tracking, expression recognition, and eye
      tracking. The treatment scheme is based on a series of therapist-guided sessions
      in which a patient communicates with FACE through an interactive console.
      Preliminary data regarding the exposure to FACE of two children are reported.

PMID- 16425834
TI  - Colon emptying induced by sequential electrical stimulation in rats.
AB  - Electrical stimulation could be used to induce colon emptying. The present
      experiments were performed to establish a stimulation pattern to optimize the
      stimulation parameters and to test neural involvement in propulsion induced by
      electrical stimulation. Colon segments were sequentially stimulated using
      rectangular pulses. The resulting propulsive activity displaced intraluminal
      content in consecutive propulsion steps. The propulsion steps differed in
      displacement latency, distance, and velocity along the stimulated colon.
      Increasing the pulse duration or amplitude resulted in a decrease of the latency.
      Increasing the stimulation amplitude doubled the displacement distance. The
      frequencies tested in the present study did not affect propulsion. Inhibition of
      cholinergic and nitrergic pathways inhibited propulsion. Electrical stimulation
      can induce colonic propulsion. Motor differences are present along the descending
      colon. The most suitable combination of pulse parameters regarding colon
      stimulation is 0.3 ms, 5 mA, 10 Hz. Neural circuits are involved in propulsion
      when using these values.

PMID- 16425835
TI  - Reliability of signals from a chronically implanted, silicon-based electrode
      array in non-human primate primary motor cortex.
AB  - Multiple-electrode arrays are valuable both as a research tool and as a sensor
      for neuromotor prosthetic devices, which could potentially restore voluntary
      motion and functional independence to paralyzed humans. Long-term array
      reliability is an important requirement for these applications. Here, we
      demonstrate the reliability of a regular array of 100 microelectrodes to obtain
      neural recordings from primary motor cortex (MI) of monkeys for at least three
      months and up to 1.5 years. We implanted Bionic (Cyberkinetics, Inc., Foxboro,
      MA) silicon probe arrays in MI of three Macaque monkeys. Neural signals were
      recorded during performance of an eight-direction, push-button task. Recording
      reliability was evaluated for 18, 35, or 51 sessions distributed over 83, 179,
      and 569 days after implantation, respectively, using qualitative and quantitative
      measures. A four-point signal quality scale was defined based on the waveform
      amplitude relative to noise. A single observer applied this scale to score signal
      quality for each electrode. A mean of 120 (+/- 17.6 SD), 146 (+/- 7.3), and 119
      (+/- 16.9) neural-like waveforms were observed from 65-85 electrodes across
      subjects for all recording sessions of which over 80% were of high quality.
      Quantitative measures demonstrated that waveforms had signal-to-noise ratio (SNR)
      up to 20 with maximum peak-to-peak amplitude of over 1200 microv with a mean SNR
      of 4.8 for signals ranked as high quality. Mean signal quality did not change
      over the duration of the evaluation period (slope 0.001, 0.0068 and 0.03; NS). By
      contrast, neural waveform shape varied between, but not within days in all
      animals, suggesting a shifting population of recorded neurons over time. Arm
      movement related modulation was common and 66% of all recorded neurons were tuned
      to reach direction. The ability for the array to record neural signals from
      parietal cortex was also established. These results demonstrate that neural
      recordings that can provide movement related signals for neural prostheses, as
      well as for fundamental research applications, can be reliably obtained for long
      time periods using a monolithic microelectrode array in primate MI and
      potentially from other cortical areas as well.

PMID- 16425836
TI  - Effects of the toe-only rocker on gait kinematics and kinetics in able-bodied
      persons.
AB  - Rocker sole shoes are commonly prescribed to diabetic patients with insensate
      feet. Recent passage of the therapeutic shoe bill has drawn an increased focus on
      prescription of rehabilitative footwear. The purpose of this work is to
      investigate the dynamics of lower extremity joints (hip, knee, and ankle) with
      the application of a toe-only rocker sole shoe under controlled laboratory
      conditions. Forty (40) normal adults volunteered for gait analysis using
      controlled baseline and prescription toe-only rocker sole shoes. Three
      dimensional motion analysis techniques were used to acquire kinematic and kinetic
      data using a six camera Vicon 370 motion system and two AMTI force plates. While
      significant changes from baseline to toe-only rocker were noted in cadence
      (increased) and stride length (decreased), no significant change in walking speed
      was observed. The most significant kinematic changes with the application of the
      toe-only shoe occurred at the ankle and knee in the sagittal plane during stance.
      The most significant kinetic effects were observed in the hip and knee during
      swing phase. Changes in power were noted at all joints, mostly in terminal
      stance. These kinematic and kinetic changes, along with previously studied
      effects of pressure relief at the metatarsal heads, should aid medical
      professionals in prescribing prophylactic footwear.

PMID- 16425837
TI  - A method for aligning trans-tibial residual limb shapes so as to identify regions
      of shape change.
AB  - Quantification of the change in shape of a residual limb over time is relevant to
      the fitting of an external prosthesis. Three algorithms were developed and
      evaluated to align residual limb shapes: iterative closest points (ICP), mean
      absolute difference, and weighted surface normals/mean absolute difference.
      Evaluations were conducted by aligning residual limb shapes with known
      deformations and transformations with their original shapes. Results showed that
      ICP did not perform well in that it tended to favor a global distribution of
      local shape difference rather than localization of the error. The mean absolute
      difference algorithm performed well as long as the shape difference was localized
      to one region. Weighted mean surface normals/absolute difference provided the
      best alignment results, performing well both if shape changes were localized and
      if they were globally distributed. Mean alignment errors for this method were
      less than 0.285 mm for each of the three translation directions and less than
      0.357 degrees for each of the three rotation directions. This algorithm could be
      helpful to patients, prosthetists, and researchers developing treatments to
      overcome the detrimental fitting effects of residual limb shape change.

PMID- 16425838
TI  - Experiments with fast Fourier transform, linear predictive and cepstral
      coefficients in dysarthric speech recognition algorithms using hidden Markov
      Model.
AB  - In this study, a hidden Markov Model was constructed and conditions were
      investigated that would provide improved performance for a dysarthric speech
      (isolated word) recognition system. The speaker dependant system was intended to
      act as an assistive/control tool. A small size vocabulary spoken by three
      cerebral palsy subjects was chosen. Fast Fourier transform, linear predictive,
      and Mel frequency cepstral coefficients extracted from data provided training
      input to several whole-word hidden Markov model configurations. The effect of
      model structure, number of states, and frame rates were also investigated. It was
      noted that a 10-state ergodic model using 15 msec frames was better than other
      configurations. Furthermore, it was found that a Mel cepstrum based model
      outperformed a fast Fourier transform and linear prediction based model. The
      system offers effective and robust application as a rehabilitation and/or control
      tool to assist dysarthric motor impaired individuals.

PMID- 16425839
TI  - A low-noise preamplifier for nerve cuff electrodes.
AB  - A single-stage, low-noise preamplifier is designed using the concept of noise
      matching for recordings of neural signal with cuff electrodes. The signal-to
      noise ratio is approximately 1.6 times higher than that of a low-noise integrated
      amplifier (AMP-01) for a cuff impedance of 1.5 komega. The bandwidth is 230 Hz
      8.25 kHz (Rs=2 komega), and the common-mode-rejection-ratio is 91.2 dB at 1 kHz.

PMID- 16425840
TI  - [Children as patients in the Kaufbeueren-Irsee Healing and Nursing Institude. The
      pediatric department 1941-5].
AB  - In the research of the history of medicine there has been little regard to
      children as patients. In this paper my focus is especially on children who were
      put in the "Kinderfachabteilung" (Children Special Department) of the Bavarian
      State Hospital of Kaufbeuren-Irsee. This is one of three "Kinderfachabteilungen"
      (Children Special Departments) in Bavaria and one of about thirty in the
      "Deutsches Reich". During the period of National Socialism these children were
      (de)classified as "lebensunwertes Leben" (life of not worth living) and as such
      were admitted to these units. They became victims of the systematically conducted
      child euthanasia. There has been the attempt to eliminate them as silent as
      possible. In the beginning I will concentrate on the development of the
      institutional history of the children's medical care in Kaufbeuren-Irsee. It will
      be presented the care of children from beginning to end (1940-1966). An analysis
      of the historical sources, a survey of children's patient records give deep
      insights into the children's fates. The emphasis will be on the
      "Kinderfachabteilung" (Children Special Department) Kaufbeuren-Irsee in which 221
      children died from 1941 to 1945.

PMID- 16425841
TI  - [A manuscript with illustrations and equipment of alchemy in the 14th century].
AB  - Manuscript 1122 Trinity College Cambridge was written in Latin in England in the
      late 13th century. Page 120verso shows drawings with descriptions of alchemistic
      vessels and apparatus. These descriptions have been deciphered, translated into
      German and commented on. Unlike many comments in literature relating to these
      drawings they neither go back to Artefius or Alphidius nor are they part of the
      paper "clavis sapientiae". They were drawn up by an unknown hand in the late 14th
      century on the empty page 120verso of the older manuscript 1122. The drawings
      show a great variety of vessels and apparatus of highly sophisticated design. It
      is clear that they are based on older, professional sources. The descriptions in
      many cases go back to Arab designations, which were later lost. In many cases,
      archaeological finds confirm the actual existence of the vessels shown in the
      manuscript, so that we can assume that the drawings represent reality. Thus the
      drawings can help to interpret finds in storerooms of museums which up to now
      have not been identified, or recently excavated parts or fragments.

PMID- 16425842
TI  - [Rokitansky as patho-philosopher].
AB  - In memory of the 200th anniversary of the eminent Austrian pathologist Carl von
      Rokitansky (1804-1874) this paper deals with his outstanding thoughts on general
      pathology as well as his own papers on different aspects of organised matter and
      some other general problems of life. In the first line Rokitansky wanted to be a
      medical practitioner, but the insufficiency of the medical practice of his time
      led him to seek a way of reform by putting pathology on a new rationalistic
      basis. Thus he eliminated all speculative elements, which had dominated pathology
      up to his time. Opposite to Rudolf Virchow, Rokitansky used materialistic methods
      only as working tools in order to bring about new results in research, but never
      became himself a materialist in thinking. Being influenced by Kant and
      Schopenhauer, Rokitansky's private philosophy tended more to idealism.

PMID- 16425843
TI  - [Several observations on delivery of Hippocatric treatises in Arabic and Greek
      tradition].
AB  - It has been known for a long time that most of the published Arabic translations
      of the Hippocratic treatises are based on the Lemmata of Galen's commentaries
      (2nd c. AC). In this paper I will discuss some philological characteristics which
      support this view but have not yet been taken into account: 1. Phrases at the
      beginning of the text (e.g. "qala"); 2. The translations are divided in chapters;
      3. Some titles which correspond to the titles of Galen's commentaries; 4. Some
      unusual phrases and omissions which can be explained by the Lemmata of the
      commentary. However, we also know of some commentaries of late antique times
      which were likewise used as a medium for the transmission of the Hippocratic
      texts. The most famous example is probably Palladios' commentary of the
      Hippocratic Aphorisms (6th c. AC). The historian al-Ya'qubi has preserved some
      fragments of this text in his Ta'rih. An investigation of the chapter
      "Hippocrates" in this Ta'rih can show that al-Ya'qabis "Vorlage" also used for
      the Prognosticon and De Diaeta two commentaries of late antique times, both of
      which are lost in the Greek tradition.

PMID- 16425844
TI  - [Cotyla quid? On the early history of late medieval medical volume calculations].
AB  - As can be made evident chiefly by their comparative numerical examination, the
      Egyptian pyramids (the step pyramids being excluded for the present purpose) have
      been, from the beginning up to the Egyptian fashion in early Imperial Rome,
      designed and built with the additional intention of physically manifesting a
      volume of pi x 10k x (average value) 0.96824 cm3, where k is either a positive
      integer or zero, and where pi is a short product, following very restrictive
      formation rules which to some extent are traceable in the papyrus Rhind, of prime
      numbers. Conceptually (but not really as to the Hin at least) this establishes
      the capacity units 1 [2]Heqat = 9682.4 cm3 and 1 Hin = 484.12 cm3 already for the
      Old Kingdom. It is shown further that the Attic Medimnos as introduced in the
      course of finishing Solon's reforms is identical with the Egyptian volume
      system's standard unification: pisigma = 2 x 3 x 5 x 7 x 11 x 23, and k = 0, so
      that 1 Medimnos = about 51443 cm3. Accordingly and by means of some adjacent
      considerations a Kotyle / Cotyla of 269 cm3 +/- 1 cm3 is established for the
      Hellenistic, early Arabic, and Medieval Latin medicine.

PMID- 16425845
TI  - [The first patient with the new variant of Creutzfeldt-Jakob's disease in The
      Netherlands].
AB  - A Dutch woman died at the age of 26 years, after a disease duration of 18 months,
      due to the new variant of Creutzfeldt-Jakob's disease (vCJD). She had never
      travelled to the United Kingdom and there was no history of potential iatrogenic
      exposure. However, she had worked in the catering and food production industry
      for the previous 6 years and had frequently consumed raw meat. The disease course
      showed the classical clinical picture of vCJD, which was confirmed by post-mortem
      examination of the brain. Contrary to classical sporadic CJD, patients with the
      variant disease are usually younger and present predominantly with psychiatric
      symptoms. Sensory complaints like pain and dysaesthesiae usually follow soon.
      Only later are these symptoms followed by rapidly progressive neurological
      symptoms and signs. All patients genotyped so far are homozygous for methionine
      on codon 129 of the prion protein gene. Recognition of the disease is of
      particular importance because of possible transmission via blood and tissues. In
      patients with rapidly progressive psychiatric symptoms and unexplained
      neurological signs, particularly sensory complaints, one must consider the
      possibility of vCJD.

PMID- 16425846
TI  - [The Nobel Prize in Physiology or Medicine for 2005 for the discovery of the
      stomach bacterium Helicobacter pylori].
AB  - This year, the Nobel Prize in Physiology or Medicine was awarded to the
      Australian doctors Marshall and Warren for their discovery and further
      identification of the stomach bacterium Helicobacter pylori. Thanks to their
      confidence in their own observations, we are now able to cure people with peptic
      ulcer disease and low-grade gastric lymphoma and are potentially able to prevent
      gastric cancer.

PMID- 16425847
TI  - [The use of age as a variable in clinical research].
AB  - There are a number of ways to study the effect of age as a variable in clinical
      research. Where survival is concerned, age is the parameter of interest. In this
      case, age-specific mortality risks, graphs of the logarithms of the age-specific
      mortality risks set against age (Gompertz-curves), life expectancies, and Kaplan
      Meier survival analysis curves are used. Confounding and effect modification by
      the age of an association between a determinant and outcome can be recognised by
      evaluating the connection between the different age groups (stratification).
      Mathematical adjustments for age in linear, logistic, and Cox regression is easy
      to carry out but their interpretation is often difficult. Adjusting for age is
      not always necessary.

PMID- 16425849
TI  - [Diagnosis image (255). A woman with a painful hand after plaster treatment].
AB  - A 22-year-old woman was treated with a plaster cast for a fifth metacarpal
      fracture of the left hand and later developed a complex regional pain syndrome.

PMID- 16425848
TI  - [Measures to reduce absorption in the treatment of intoxications].
AB  - New guidelines on gastrointestinal decontamination in overdose situations have
      been published. In cases of serious and potentially life-threatening
      intoxication, gastric lavage can be performed up to 1 hour after ingestion. It
      should not be considered as routine treatment. If a patient has ingested a
      potentially toxic amount of a poison which is known to be absorbed by charcoal,
      single-dose activated charcoal in powder form may be considered up to 1 hour
      after ingestion. After ingestion of a potentially lethal amount of a toxin that
      is travelling through the enterohepatic or entero-enteral circulation, multiple
      dose activated charcoal can be considered. The efficacy of carbamazepine,
      theophylline, quinine, dapsone and phenobarbital has been proven. In the
      treatment of potentially life-threatening intoxications with sustained-release
      preparations or drug-filled packages, particularly after ingestion of substances
      that do not bind to activated charcoal, whole bowel irrigation can be considered.
      Only ifdefaecation is insufficient should administration of a laxative together
      with activated charcoal be considered.

PMID- 16425850
TI  - [From gene to disease; MutYH-associated polyposis coli (MAP)].
AB  - MutYH-associated polyposis coli (MAP) is an autosomal recessive inherited form of
      polyposis and colorectal carcinoma associated with germline mutations in the
      MutYH gene on chromosome I. The MutYH protein is a base excision repair
      glycosylase which is involved in the repair of damage caused by the oxidation ofa
      guanine leading to 8-oxo-7,8-dihydroguanine. If the MutYH protein is
      dysfunctional, G:C --> T:A mutations in the APC-gene give rise to polyposis and
      in 50-60% of cases also colorectal carcinoma. MutYH polyposis differs from
      familial adenomatous polyposis coli in its mode of transmission, later age of
      onset, a less florid form of polyposis, and fewer extra colonic manifestations.

PMID- 16425851
TI  - [Lifestyle of Dutch people aged 55-64 years less healthy in 2002/'03 than in
      1992/'93].
AB  - OBJECTIVE: To describe the lifestyle of men and women aged 55-64 years in The
      Netherlands in 2002/'03 and compare it with the lifestyle of people of the same
      age in 1992/'93. DESIGN: Descriptive. METHOD: Data were used from the
      Longitudinal Aging Study Amsterdam. The study comprised two randomly selected
      samples from local municipal registers in 1992/'93 (n = 966) and 2002/'03 (n =
      1002), stratified according to sex, age and expected 5-year survival.
      Participants were from 11 municipalities in the west, northeast and south of The
      Netherlands. Data were collected from interviews, measurements and a written
      questionnaire. The response was 62% in 1992/'93 and 57% in 2002/'03. RESULTS: In
      1992/'93, 9.5% of the men and 20.5% of the women were obese. Ten years later
      these percentages were 18.4 and 27.5. The percentage of current smokers was
      stable over time and included one-third of men and one-quarter of women. More
      people used alcohol in 2002/'03; excessive alcohol use was found in 15.7% of the
      men (11.7% in 1992/'93) and 19.5% of the women (11.1% in 1992/'93). The energy
      expended through walking, bicycling, household activities and sports was one
      fifth less in 2002/'03. CONCLUSION: The lifestyle of people aged 55-64 years in
      The Netherlands was less healthy in 2002/'03 than in 1992/'93. Because positive
      changes in lifestyle can reduce the risk of chronic diseases, functional
      limitations and early death, more attention to healthy living is necessary in
      this age group.

PMID- 16425852
TI  - [Obstructive jaundice caused by portal varicosis].
AB  - In a 66-year-old woman with pruritus, jaundice, dark-brown urine and light
      colored faeces obstructive jaundice was diagnosed. Despite extensive
      investigations, it was not possible to clearly distinguish if varicosis or
      cholangiocarcinoma was the cause of the obstruction. During laparotomy the right
      lobe of the liver was seen to be greatly underdeveloped. The portal system showed
      a varicose deformation with compression of the bile ducts and portal
      hypertension. The right lobe of the liver was removed and the portal hypertension
      was treated by creating a shunt between the hepatic portal vein and the right
      ovarian vein. The jaundice disappeared and the patient recovered. Histological
      investigation showed atrophy, secondary biliary fibrosis, cirrhosis and a biliary
      cystadenoma. There were no signs of malignancy. The varicose deformation can be
      considered to be a result of the portal hypertension caused by fibrosis and
      cirrhosis with possibly a history of thrombosis and insufficient recanalization.

PMID- 16425853
TI  - [Haemorrhagic colitis in a young male after the use of amoxicillin].
AB  - A 16-year-old boy had rectal blood loss due to haemorrhagic colitis probably
      resulting from oral and intravenous administration of amoxicillin. He also had
      haemolytic anaemia and thrombocytopenia, both also most likely resulting from the
      use of amoxicillin and/or ibuprofen. In the week following the discontinuation of
      amoxicillin and ibuprofen, the symptoms of bloody diarrhoea disappeared
      spontaneously and the blood picture became normal. Haemorrhagic colitis is a
      known side effect of amoxicillin that is rarely seen. Discontinuation of
      treatment typically results in a quick and uneventful recovery.

PMID- 16425855
TI  - [Sharp increase of infections with Salmonella serotype Typhimurium DT104 in The
      Netherlands].
AB  - Salmonella remains an important source of food-related outbreaks of gastro
      enteritis. In The Netherlands, regional laboratories send cultured Salmonella
      isolates to the National Institute of Public Health and the Environment (RIVM)
      for sero- and phage typing. Abnormal increases in the incidence of Salmonella
      infections are monitored by means of surveillance. Since the middle of September
      2005, there has been a sharp increase in Salmonella Typhimurium DT104 (Dutch
      phage type 506 and 401) isolates, from all parts of the country and mainly from 6
      to 20-year-olds. Since a first series of telephone interviews did not yield a
      clear source of the outbreak, a more extensive, written study has been started in
      a larger group of patients and corresponding controls.

PMID- 16425854
TI  - [G. A. van Rijnberk (1875-1953): key figure in Dutch medicine in the interbellum
      period].
AB  - G. A. van Rijnberk (1875-1953) was Dutch by birth but attended school in Italy
      and studied medicine there. He received his training as a scientific researcher
      in Rome from the famous physiologist Luciani. During the time that he spent at
      Luciani's Institute, he managed to gain attention for himself through his
      scientific work. In 1909 the University of Amsterdam appointed Van Rijnberk as a
      professor of physiology. He continued to produce scientific work during the first
      decade of his professorship but later focused on writing textbooks and his
      responsibilities as managing editor of The Nederlandsch Tijdschrift voor
      Geneeskunde (Dutch Journal of Medicine) (1913-1946). In this role and over the
      course of the years he acquired the reputation of an autocrat who left his mark
      on the Journal's policies. This was apparent in his attention to correct language
      use, interest in the history of medicine and the construction of a library.
      Thanks to his efforts, the weekly clinical lesson has been a regular feature
      since 1928. The property on Jan Luykenstraat acquired under Van Rijnberk's
      management would remain the headquarters of the Journal for more than half a
      century. Van Rijnberk was also active as a columnist in the lay press and as an
      author of books on occultism.

PMID- 16425856
TI  - [Haemodialysis in Turkey].
AB  - In Izmir, Turkey's third largest town, remarkably good treatment results have
      been achieved in haemodialysis patients. This success has been achieved by the
      formation of a close-knit and durable team of physicians and nurses at Ege
      University. This has enabled patients to be treated using a strict volume-control
      method and to be given individual attention and psychosocial support. This has
      been made possible by close collaboration with a producer of dialysis machines.
      Possible conflicts of interest were avoided as there were no personal connections
      between physicians and the production sector.

PMID- 16425857
TI  - [Bruises, loose teeth and fatigue in a patient with schizophrenia].

PMID- 16425858
TI  - [Adenotonsillectomy in children only under exceptional circumstances].

PMID- 16425859
TI  - [Heredity and psychology predict the result of herniated disk surgery].

PMID- 16425860
TI  - [Asthma-like conditions still not completely mapped. Capsaicin may give a
      differential diagnosis--but is not yet ready for clinical use].

PMID- 16425861
TI  - [Dietary guidelines should be evidence-based. Diabetes can be
      prevented/controlled with balanced diet].

PMID- 16425862
TI  - [Asthma--a disease difficult to define. Patients can receive correct treatment by
      means of differential diagnosis criteria].
AB  - Asthma is a well defined disease in international consensus reports. However, in
      clinical praxis patients are often presenting asthma-like symptoms that are not
      explained by asthma and not by chronic obstructive pulmonary disease (COPD), the
      later being reported as the most common differential diagnosis. In an asthma and
      allergy clinic the most common differential diagnoses are asthma-like disorders,
      of which sensory hyperreactivity (SHR) can be identified by a capsaicin
      inhalation test. This review presents aspects on the investigation of adult
      patients with airway symptoms based on 20 years of clinical studies. It is
      pointed out that a careful asthma investigation strictly following diagnostic
      criteria is the first step. After this further diagnostic steps may be taken,
      especially as sensory mechanisms are often involved. Sensory hyperreactivity may
      also be present in patients with "classical" asthma sometimes explaining the lack
      of effect of asthma medication.

PMID- 16425863
TI  - [Premature infants benefit from inhaled nitric oxide, too. Not only full-term
      infants with severe hypoxic respiratory failure].

PMID- 16425864
TI  - [Nerve injuries in the hand].

PMID- 16425865
TI  - [Highly important during Christmas holidays. Elderly persons are overrepresented
      when it comes to candle light fires].

PMID- 16425866
TI  - [Three kinds of love--the prerequisite for continued human existence].

PMID- 16425867
TI  - [Are we all deceived? About exaggerations, secrets and lies in health care].

PMID- 16425869
TI  - [Low carbohydrate diet should be tested when the traditional one does not help].

PMID- 16425868
TI  - [Are physicians free to give any kinds of dietary recommendations?].

PMID- 16425870
TI  - [Rigid training support rules are unfair to both students and the society].

PMID- 16425871
TI  - [SBU presents ill-founded conclusions on the treatment of anxiety].

PMID- 16425872
TI  - [Effective self care of lymphedema].

PMID- 16425877
TI  - [Does esthetic surgery exist?].

PMID- 16425878
TI  - [Congenital giant nevus, when to operate?].

PMID- 16425879
TI  - [Margaux, a little girl with a giant nevus].

PMID- 16425880
TI  - [Cleft lips and palates, a multidisciplinary management].

PMID- 16425881
TI  - [Left maxillary chondroblastic osteosarcoma].

PMID- 16425882
TI  - [Needs of children and adolescents during esthetic and reconstructive surgery].

PMID- 16425883
TI  - [Plastic and reconstructive surgery, what management for adolescents?].

PMID- 16425884
TI  - [Breast feeding or holding an infant against oneself].

PMID- 16425885
TI  - [Early childhood health policy in Switzerland].

PMID- 16425886
TI  - [Organization of care in neonatology in France].

PMID- 16425887
TI  - [Offering a prepartum consultation].

PMID- 16425888
TI  - [The soul of the fetus].

PMID- 16425889
TI  - [Germany after PISA--7 theses to the school situation].

PMID- 16425890
TI  - [Counseling as responsibility in nursing].

PMID- 16425891
TI  - [Wish for children at any price? Possibilities and limits of reproduction
      medicine].

PMID- 16425892
TI  - [Interview with Dr. Tewes Wischmann of the German Counseling Network Wish for
      Children (interview by Kristina Rickmers)].

PMID- 16425893
TI  - [Two worlds promote connection: preventive health care as also a chance for
      professional autonomy in pediatric nursing].

PMID- 16425894
TI  - [Occultism in children and adolescents. Search movements by youth for an
      orienting world view and possible transcendence--theological observations and
      reflections].

PMID- 16425896
TI  - [Each person is the closest to himself].

PMID- 16425895
TI  - [Hand eczema is preventable. A "thicker skin" helps to achieve healthy skin].

PMID- 16425897
TI  - ["My younger brother is fatally ill. Grief of siblings].

PMID- 16425898
TI  - New drugs for peripheral joint psoriatic arthritis.
AB  - Up to 3% of people have psoriasis, and as many as 42% of these have an associated
      chronic inflammatory arthritis. In up to 20% of such patients, the arthritis
      progresses to become severe, destructive and deforming. Traditional drug
      treatments include NSAIDs and disease-modifying anti-rheumatic drugs (DMARDs)
      used for rheumatoid arthritis. Leflunomide (Arava - Sanofi-Aventis), etanercept
      (Enbrel - Wyeth) inifliximab (Remicade - Schering-Plough) and adalimumab (Humira 
      Abbott) are licensed for the treatment of patients with peripheral joint disease
      in psoriatic arthritis. Here we review drug therapy for such patients,
      concentrating on the newer agents.

PMID- 16425899
TI  - Drotrecogin alfa (activated) for severe sepsis.
AB  - Sepsis, the systemic inflammatory response to infection, is common among severely
      ill patients and can be life-threatening. Over a quarter of patients in UK
      intensive care units (ICUs) have severe sepsis in the first 24 hours after
      admission. Of these, 35% die before leaving the ICU and 47% before leaving
      hospital despite standard therapy. Drotrecogin alfa (activated) (Xigris - Eli
      Lilly), a recombinant human activated protein C, is licensed for treating adults
      who have severe sepsis with multiple organ failure. Here we assess its efficacy
      and safety.

PMID- 16425900
TI  - Constructing a morality of caring: codes and values in Australian carer
      discourse.
AB  - In this analysis I apply a Foucauldian approach to ethics to examine the
      politically prescribed moral and ethical character required of carers of aged
      persons at home in Australia and the role of nurses in shaping these behaviours.
      The work that spousal carers provide, although often founded on love and/or
      obligation, has been formalized through a variety of policy initiatives and
      technologies that serve to construct the moral approach they must adopt. This
      shaping of conduct at the most personal level takes place through the application
      of codes of behaviour policed largely by nurses. These codes redefine the mode of
      coexistence between an aged husband and wife and propose a new form of
      relationship that is derived from and supports policies of the
      deinstitutionalization of care services for elderly persons. In this way modern
      carer policy has drawn on knowledge and governance of the self to produce a
      morality of caring that is both authoritative and scientific.

PMID- 16425901
TI  - Learning to respect a patient's spiritual needs concerning an unknown infectious
      disease.
AB  - This article aims to help readers to learn about health care related cultural and
      religious beliefs and spiritual needs in Chinese communities. The recall diary of
      a severe acute respiratory syndrome (SARS)-infected intern working in Hoping
      Hospital in Taiwan during the 2003 SARS epidemic is presented and used to assist
      in understanding one patient's spiritual activities when personally confronted
      with this newly emerging infectious disease. The article also gives an overview
      of the 2003 SARS epidemic in Taiwan, and discusses people's general perceptions
      towards infectious diseases, their coping strategies concerning disease, and
      their spiritual beliefs, the psychological impact of the 2003 SARS outbreak in
      Chinese communities, Chinese myths about infectious disease, and the religious
      activities of a SARS-infected intern in Taiwan. Recommendations are given on how
      to achieve quality holistic nursing care.

PMID- 16425902
TI  - The caring relationship in hospice care: an analysis based on the ethics of the
      caring conversation.
AB  - Good nursing is more than exercising a specific set of skills. It involves the
      personal identity of the nurse. The aim of this article is to answer two
      questions: (1) what kind of person should the hospice nurse be? and (2) how
      should the hospice nurse engage in caring conversations? To answer these
      questions we analyse a nurse's story that is intended to be a profile of an
      exemplary hospice nurse. This story was constructed from an analysis of five
      semistructured interviews with hospice nurses, based on the 'ethics of the caring
      conversation', which is inspired by the ethical perspective of Paul Ricoeur. The
      research questions concentrate on the norms of respect, responsibility and
      reciprocity, which are integral parts of the 'ethics of the caring conversation'.

PMID- 16425903
TI  - Finnish nurses' interpretations of patient autonomy in the context of end-of-life
      decision making.
AB  - Our aim was to study how nurses interpret patient autonomy in end-of-life
      decision making. This study built on our previous quantitative study, which
      evaluated the experiences of and views on end-of-life decision making of a
      representative sample of Finnish nurses taken from the whole country. We
      performed qualitative interviews with 17 nurses and analysed these using
      discourse analysis. In their talk, the nurses demonstrated three different
      discourses, namely, the 'supporter', the 'analyst' and the 'practical'
      discourses, each of which outlined a certain position for patients and relatives,
      and a certain identity for the nurses in end-of-life decision making. The nurses'
      talk showed notable differences when compared with that of physicians,
      highlighting the differences that take place in respect of the image of a
      person's work, professional culture, professional identification and
      responsibilities. An important finding was that the nurses often described their
      participation in end-of-life decision making in terms of indirect influence.

PMID- 16425904
TI  - Nurses as moral practitioners encountering parents in neonatal intensive care
      units.
AB  - Historically, the care of hospitalized children has evolved from being performed
      in isolation from parents to a situation where the parents and the child are
      regarded as a unit, and parents and nurses as equal partners in the child's care.
      Parents are totally dependent on professionals' knowledge and expertise, while
      nurses are dependent on the children's emotional connection with their parents in
      order to provide optimal care. Even when interdependency exists, nurses as
      professionals hold the power to decide whether and to what extent parents should
      be involved in their child's care. This article focuses on nurses' responsibility
      to act ethically and reflectively in a collaborative partnership with parents. To
      illuminate the issue of nurses as moral practitioners, we present an observation
      of contemporary child care, and discuss it from the perspective of the Danish
      moral philosopher KE Logstrup and his book The ethical demand.

PMID- 16425905
TI  - How nursing ethics as a subject changes: an analysis of the first 11 years of
      publication of the journal Nursing Ethics.
AB  - By analysing the first, second, 10th and 11th years of publication (i.e. volumes
      1, 2, 10, 11) of Nursing Ethics, I will show the significant visible trends in
      the articles and draw some conclusions. The trends are visible at various levels:
      from simple analysis of an issue, or a comment on a situation in the early years,
      to in-depth philosophical and research studies; and from short statements to much
      longer articles. The ethical approaches used go from either none or unquestioned
      assumptions to several approaches used in any one study. This corresponds to the
      general postmodern trend in society. The interpretation made of these trends is
      of a kind of protest at nurses and nursing being devalued. Although this is
      expressed negatively, the positive message conveyed is that nurses are now taking
      their professional life into their own hands, vigorously and more daringly than a
      decade ago.

PMID- 16425906
TI  - A visit to the Buddhist Tzu Chi General Hospital in Hualien, Taiwan.

PMID- 16425908
TI  - Health care utilization for unintentional poisoning.

PMID- 16425907
TI  - Viste will be missed.

PMID- 16425909
TI  - Counterpoint: concealed carry legislation.

PMID- 16425910
TI  - Clinical Questions #6. Does celecoxib increase cardiovascular risk?

PMID- 16425911
TI  - Society must lead the way in reforming health care system.

PMID- 16425912
TI  - Starting the health care debate in Congress.

PMID- 16425913
TI  - Should Wisconsin finance health care through a special tax and a voucher system?

PMID- 16425914
TI  - The Wisconsin Health Plan.

PMID- 16425915
TI  - The Wisconsin Health Care Plan: a practical, effective, and comprehensive
      response to our health care crisis.

PMID- 16425916
TI  - The Wisconsin Health Security Act: a necessity for people, business, and the
      economy.

PMID- 16425917
TI  - Affordable health care: a local solution.

PMID- 16425918
TI  - Co-op care: using cooperative principals to add value to health care.

PMID- 16425919
TI  - Wisconsin Medical Society Health System Reform Plan.

PMID- 16425920
TI  - The New Wisconsin Idea: a prescription for health care system reform.

PMID- 16425921
TI  - The health care conundrum: providing access to the uninsured while balancing
      costs.

PMID- 16425922
TI  - Affordable health care practiced here.

PMID- 16425923
TI  - Emergency department visits in Wisconsin 1998-2002: trends in usage and accuracy
      of reported data.
AB  - INTRODUCTION: There is a paucity of data regarding the utilization of emergency
      departments (EDs) across Wisconsin. It is unknown if national trends in increased
      utilization are consistent within our state. Several years ago, mandatory
      reporting of ED visits to the Department of Health and Family Services was
      instituted and, if accurate, may provide a method for tracking ED usage. METHODS:
      We conducted a survey of existing EDs to study the trend in patient visits for
      the 5-year time period 1998-2003. Data reported in the surveyed departments were
      compared to those reported to the state database. RESULTS: On average, all EDs
      reported a consistent yearly increase in patient visits over the time period (an
      average overall increase of 10%). On average, this increase was larger for
      smaller hospitals. Growth was consistent over the time period, but the yearly
      rate steadily slowed down. Data reported to the state consistently underreported
      the actual census. CONCLUSION: All sizes of EDs across Wisconsin continue to show
      increases in ED utilization. The growth rate is consistent but may be slowing.
      This has implications for planning for ED resources. Reported data have many
      discrepancies and need to be independently checked before they can be utilized in
      any research or planning.

PMID- 16425924
TI  - Low bone mass prevalence and osteoporosis risk factor assessment in African
      American Wisconsin women.
AB  - BACKGROUND: Post-menopausal osteoporosis is seen in all racial groups. With the
      increasing population and longevity of minority groups, osteoporosis is becoming
      an important health concern. Data regarding risk factors for, and prevalence of,
      low bone mass and awareness of osteoporosis risk in African American (AA) women
      are limited. OBJECTIVE: This article evaluates the risk factors for, and
      prevalence of, low bone mass in a population of urban AA women in Wisconsin and
      assesses this group's perceived risk for osteoporosis. METHODS: One hundred fifty
      consecutive community-dwelling AA women > or = 45 years old from Milwaukee, Wis
      were asked to complete a questionnaire based on currently accepted osteoporosis
      risk factors. Additionally, their perception of osteoporosis risk was assessed
      using a Likert scale. All subjects underwent quantitative calcaneal ultrasound.
      RESULTS: Subject mean age was 54 +/- 7 years. Mean T- and Z-scores were 0.5 and
      0.4, respectively. Applying World Health Organization criteria, osteopenia (bone
      mineral density T-score <-1.0) was present in 23.3% and osteoporosis (bone
      mineral density <-2.5) in 9.3%. Multivariate analysis of risk factors showed that
      lifetime incidence of at least 1 fracture, multiparity (>2 children),
      postmenopausal state, and current smoking were associated with lower calcaneal
      bone mass. Higher education and presence of diabetes were associated with a
      higher bone mass. Only 25% of the women surveyed thought they were at moderate to
      high risk for osteoporosis. CONCLUSIONS: Low bone mass was present in 33% of
      these AA women despite their relative young age. Many AA women do not perceive
      osteoporosis as a health risk. It is necessary to develop strategies to educate
      AA women regarding osteoporosis risk.

PMID- 16425925
TI  - The increasing incidence of end-stage renal disease in Wisconsin from 1982-2003:
      an analysis by age, race, and primary diagnosis.
AB  - PURPOSE: To examine the trends in the incidence of end-stage renal disease in
      Wisconsin from 1982 to 2003. METHODS: De-identified incidence data for this study
      were supplied by the Renal Network of the Upper Midwest (Region 11). We examined
      trends in the incidence of end-stage renal disease by age, race, gender, and
      primary diagnosis from 1982 to 2003. RESULTS: The incidence of end-stage renal
      disease increased more than 3-fold from 1982 to 2003. This increase was
      especially striking in persons with diabetes and hypertension, as well as among
      those aged > or = 75 years. The increase in the incidence of end-stage renal
      disease was also apparent among all racial groups and both genders. CONCLUSIONS:
      The continued increase in the incidence of end-stage renal disease in Wisconsin
      may result from a number of factors, such as an unintended consequence of better
      chronic disease management, which may predispose older individuals to end-stage
      renal disease. Resources aimed at decreasing the incidence of end-stage renal
      disease are needed to prevent unnecessary health care costs and negative health
      outcomes, including loss of life.

PMID- 16425927
TI  - Taking the lead locally to address our urgent national problem.

PMID- 16425926
TI  - A challenging patient, an innovative solution.
AB  - This report of the management of a 28-year-old patient over 2 and a half years
      illustrates how interaction between psychosocial issues and physical symptoms
      complicates diagnosis and management. The case also highlights the challenges
      inherent in a large health care system with multiple health care professionals,
      clinics, and available resources. A "team model" approach is outlined as a useful
      strategy in such cases. Once problem areas are defined, a partnership agreement
      (contract) is recommended, which applies structure and limits to the physician
      patient relationship. This contract calls for mutual trust, communication, and
      accountability while preventing excessive use of the health care system. Our
      patient and hospital system greatly benefited by this approach as evidenced by
      (1) a 60% decrease in medication costs, (2) markedly decreased ED visits and
      telephone calls, (3) successful treatment of depression and anxiety, and (4) a
      positive outcome on the patient's health.

PMID- 16425928
TI  - Are you protecting your most valuable asset?

PMID- 16425929
TI  - The 100,000 Lives Campaign.

PMID- 16425930
TI  - To cure a cold. 1905.

PMID- 16425931
TI  - Here we go again.

PMID- 16425932
TI  - The rough and tumble life.

PMID- 16425933
TI  - Menactra, Boostrix and ADACEL; new vaccines for 2005.

PMID- 16425934
TI  - Medical students learn policy and advocacy through annual Legislative Day.
AB  - Through the collaborative relationship of the South Dakota State Medical
      Association (SDSMA) and the University of South Dakota School of Medicine
      (USDSM), there has been increased awareness and interest among medical students
      in the legislative process and its effect on the practice of medicine and
      delivery of care. As a result of this educational interest, and through the
      collaboration of these organizations, a formal "Legislative Day" has been added
      to the USDSM curriculum.

PMID- 16425936
TI  - COX-2 inhibitors and the risk for cardiovascular events: a re-evaluation of the
      data and proposed mechanisms.

PMID- 16425935
TI  - Baseball and my dad.

PMID- 16425937
TI  - Ballot initiative.

PMID- 16425938
TI  - Endometrial ablation for dysfunctional uterine bleeding.

PMID- 16425939
TI  - Monteggia fractures: beware!
AB  - Monteggia fractures consist of an ulna fracture accompanied by radial
      dislocation. These fractures are easily overlooked because of the prominence of
      the ulnar fracture. Furthermore, the leading cause of malpractice cases brought
      against emergency departments involve missing high-risk orthopedic injuries, such
      as Monteggia fractures. The purpose of this article is to provide sufficient
      information to reduce the possibility of underestimating forearm injuries and,
      consequently, diagnose a Monteggia fracture correctly. This article outlines the
      classification of Monteggia fractures, the mechanism of injury, a specific case
      report, and a discussion of consequences when the extent of the injury is
      underestimated. Finally, specific ways are presented to easily avoid the
      misjudgment of a Monteggia fracture.

PMID- 16425940
TI  - The Walter C. Randall Lecture: embryos, cloning people and stem cell research.

PMID- 16425941
TI  - Who will be providing primary care in 20 or 30 years?

PMID- 16425942
TI  - Jody's job.

PMID- 16425943
TI  - South Dakota pain surveys: results from 2001.
AB  - Concerns about pain management in South Dakota generated survey research in 2001.
      Knowledge of and attitudes toward pain management were assessed through a survey
      of health care professionals, and standards of practice and education efforts in
      the area of pain management were evaluated by a questionnaire sent to South
      Dakota health care facilities. Results show gaps in knowledge, attitudes that
      hamper adequate treatment of acute and chronic pain, and the need for a seamless
      approach to standards of practice in pain management for health care facilities.
      Results and recommendations for interventions and future research are discussed.

PMID- 16425944
TI  - Inactivated influenza vaccine: what you need to know.

PMID- 16425945
TI  - Ezetimibe: a turbocharger for the race to reach NCEP LDL goals.

PMID- 16425946
TI  - [Merging adult intensive care units in Geneva and Lausanne: a cultural
      revolution?].

PMID- 16425947
TI  - [The management of the alcohol withdrawal syndrome in the intensive care unit].
AB  - The management of the alcoholic withdrawal syndrome in the intensive care unit is
      difficult. Clearly, the patient must be sedated, in order to avoid the side
      effects of agitation, like trauma. However, a too much enthusiastic sedation has
      to be avoided, first because it may unmask neurologic important information, and,
      second, because it can prolong or complicate the ICU stay. In this review, we
      discuss the actual management of the alcoholic withdrawal syndrome in the ICU.

PMID- 16425948
TI  - [To integrate patient's preferences in intensive care treatment plans].
AB  - An increasing number of terminally ill patients are admitted into the intensive
      care unit, and decisions of limitation, or of palliative care are made to avoid
      medical futility. The principle of autonomy states that the patient (or in case
      of necessity his relatives) should make end of life decision after detailed
      information. The exercise of autonomy is difficult due to the disease of the
      patient and the nature of invasive treatments, but also due to organisational and
      communication barriers. The latter can be surmounted by a proactive approach.
      Early communication with the patient and relatives about the sometimes-limited
      expectations of an invasive treatment plan, and the possibility of palliative
      care allow to integer patient's preferences in the formulation of a therapeutical
      plan.

PMID- 16425949
TI  - [Management of status epilepticus in intensive care].
AB  - Status epilepticus (SE) is an emergency situation for the neurologist as for the
      critical care physician, because it is caused by a focal or by a generalized
      severe brain suffering. Therefore, SE must be treated as soon as possible. The
      management, beyond a rapid and accurate diagnosis, must include the
      identification of the cause of SE, whereas seizures must be rapidly stopped.

PMID- 16425950
TI  - [Strategies targeted at optimising antimicrobial therapy in critically ill
      patients].
AB  - Antibiotics are widely used in critical care and adequate empirical treatments
      has a significant impact on the outcome of many patients. Most nosocomial
      infections may be due to multidrug-resistant pathogens and requires empirical
      borad spectrum coverage before identification of the etiologic agents. This is
      associated with overuse of antibiotics which contributes to the further increase
      in multidrug-resistances. In this context, new strategies targeted at antibiotic
      control, such as guidelines and de-escalation are needed to control this
      evolution.

PMID- 16425951
TI  - [Intensive care unit admission of critically ill cancer patients].
AB  - Admission, and non-admission, in intensive care units (ICU) for oncologic
      patients are discussed in this review. Medical, ethical and economical concerns
      have to be considered. We are in favor of a flexible attitude, aimed at avoiding
      two pitfalls: first, not to allow to a patient to benefit of intensive treatment
      when available and useful, and, second, to impose to a patient difficult and
      painful therapy if the survival chance is minimal. The patient must be a partner
      for the decision to admit him or her in the ICU. In addition, it is important to
      be aware that, during the last few years, the prognosis of the oncologic patients
      treated in the ICU is continuously improving. Therefore, the admission of such
      patients must be systematically discussed with both the oncologist and the
      critical care physician.

PMID- 16425952
TI  - [Thoracic surgery and underfeeding scientific evidences, diagnosis and
      treatment].
AB  - Underfeeding causes a significant increase of postoperative complications,
      particularly respiratory and infectious complications. Thoracic surgery is
      frequently required in patients suffering wasting diseases (cancer, COPD, cystic
      fibrosis), which increase the risk of malnutrition. The most important risk
      factors are preoperative hypoalbuminemia and BMI < 20. The deleterious effects of
      underfeeding may be corrected by a preoperative nutritional support for 7 to 15
      days using oral supplements or enteral feeding: respiratory muscle strength is
      improved, immunity is restored, and overall complications are reduced. Therefore
      preoperative diagnosis of underfeeding is of utmost importance. In case of
      emergency surgery, the nutritional assessment on admission enables the
      introduction of early postoperative artificial feeding.

PMID- 16425953
TI  - [Geneva commission on health personnel surveillance: recent legal actions ].

PMID- 16425954
TI  - [The 2005 ribbon of the fight against AIDS].

PMID- 16425955
TI  - [The hospital physician and the fate of the sick].

PMID- 16425956
TI  - [Two United Nations agencies look into the problem of our eggs and poultry].

PMID- 16425957
TI  - [HIV antiretroviral agents: new threats to accessibility in developing
      countries].

PMID- 16425958
TI  - [Learning to cope with death].

PMID- 16425959
TI  - Hematologic complications of HIV infection.
AB  - Treatment of HIV-infected patients with highly active antiretroviral therapy
      (HAART) has altered the natural history of human immunodeficiency virus (HIV)
      infection by decreasing the frequency of opportunistic infections and altering
      the expected frequency of hematologic complications and AIDS-related
      malignancies. Thrombotic thrombocytopenic purpura and thrombosis resulting from
      protein S deficiency are relatively rare complications of HIV in the United
      States in patients taking HAART, but are frequent in the developing world where
      these drugs are not available. Cytopenia, particularly anemia, are more common
      and result both from bone marrow failure and peripheral destruction. Hodgkin's
      and non-Hodgkin's lymphoma are still problematic in patients with advanced
      disease with high viral loads. This review will examine and discuss the diagnosis
      and management of the hematologic complications of HIV.

PMID- 16425960
TI  - Liver steatosis in HIV-infected patients.
AB  - Liver steatosis, defined as abnormal fat accumulation in hepatocytes, may be
      related to different pathogenic mechanisms, in particular metabolic
      abnormalities, toxic injuries, and viral infections. Since most of these
      mechanisms are frequently encountered in HIV-infected patients, and since HIV
      infection per se and antiretroviral treatments may be involved in the
      pathogenesis of liver steatosis, it could be speculated that HIV-infected
      patients are at a high risk of developing the condition. However, studies on
      steatosis in HIV-infected patients are still rare and do not reveal any
      significant increase, prevalence or clinical impact. Nevertheless, while waiting
      for prospective studies in HIV-infected patients, improved recognition, diagnosis
      and management of steatosis are required in these patients.

PMID- 16425961
TI  - Molecular epidemiology of HIV-1 variants in the global AIDS pandemic: an update.
AB  - The picture of HIV-1 genetic diversity in the global pandemic continues to
      evolve. Identification of new variants, including circulating and unique
      recombinant forms, recognition of new outbreaks and of changes in established
      epidemics, and characterization of growing numbers of full-length genomes provide
      a view of high dynamism and increasing complexity. The pervasive role of
      recombination as a major driving force in the generation of diversity in the HIV
      1 pandemic is becoming evident, and is particularly visible in areas in which
      different genetic forms meet, referred to as "geographic recombination hotspots".
      The importance of superinfection and its impact on HIV-1 diversification and
      propagation is surfacing, although restrictions to superinfection are also
      apparent. Genetic diversity within subtypes is increasing over time and new
      geographically localized lineages deriving from point introductions are being
      recognized. Characterization of such variants may be of relevance to vaccine
      development and may allow the detection of intrasubtype recombination and
      superinfection. Recent studies supporting the correlation of HIV-1 clades to
      immune responses and to drug resistance-associated mutations lend increasing
      relevance to the role of molecular epidemiology as an essential tool in combating
      the AIDS pandemic. However, knowledge on the global HIV-1 genetic diversity and
      its implications is still far from adequate and a major scaling up of efforts is
      needed.

PMID- 16425962
TI  - Predictors of virologic response to ritonavir-boosted protease inhibitors.
AB  - The primary mechanism of resistance to protease inhibitors involves the stepwise
      accumulation of mutations that alter and block the substrate binding site of HIV
      protease. The large degree of cross-resistance among the different protease
      inhibitors is a source of considerable concern for the management of patients
      after treatment failure. Although the output of HIV-resistance tests has been
      based on therapeutically arbitrary criteria, there is now an ongoing move towards
      correlating test interpretation with virologic outcomes on treatment. This
      approach is undeniably superior, in principle, for tests intended to guide drug
      choices. However, the predictive accuracy of a given stratagem that links
      genotype or phenotype to drug response is strongly influenced by the study
      design, data capture and the analytical methodology used to derive it. There is
      no definitively superior methodology for generating a genotype-response
      association for use in interpreting a resistance test, and the various approaches
      used to date all have their strengths and weaknesses. Combining the information
      of therapeutic drug monitoring and resistance tests is likely to be of greatest
      clinical utility in antiretroviral-experienced patients harboring HIV strains
      with reduced susceptibility. The combination of pharmacologic and virologic
      parameters as a predictor of the virologic response has been merged into the
      parameter known as "inhibitory quotient". This article discusses the potential
      interest of the use of inhibitory quotients as an approach for enhancing the
      potency and durability of boosted protease inhibitors against protease inhibitor
      resistant viruses.

PMID- 16425963
TI  - Maedi-visna virus and its relationship to human immunodeficiency virus.
AB  - Maedi-visna is a slow virus infection of sheep leading to a progressing
      lymphoproliferative disease which is invariably fatal. It affects multiple
      organs, but primarily the lungs where it causes interstitial pneumonia (maedi).
      Infection of the central nervous system was commonly observed in Icelandic sheep
      (visna), infection of mammary glands (hard udder) in sheep in Europe and the USA,
      and infection of the joints in sheep in the USA. The name ovine progressive
      pneumonia (OPP) is commonly used in the USA and ovine lentivirus (OvLV) infection
      is also a name used for maedi-visna. A related infection of goats, caprine
      arthritis-encephalitis (CAE), is common in Europe and the USA. The natural
      transmission of maedi-visna is mostly by the respiratory route, but also to
      newborn lambs by colostrum and milk. Intrauterine transmission seems to be rare
      and venereal transmission is not well documented. Macrophages are the major
      target cells of maedi-visna virus (MVV), but viral replication is greatly
      restricted in the animal host, apparently due to a posttranscriptional block. The
      low-grade viral production in infected tissues can explain the slow course of the
      disease in sheep. The lesions in maedi-visna consist of infiltrates of
      lymphocytes, plasma cells, and macrophages, and are detectable shortly after
      experimental transmission. Several studies indicate that the lesions are immune
      mediated and that cytotoxic T-lymphocytes may be important effector cells. The
      persistence of the MVV infection is explained by a reservoir of latently infected
      blood and bone marrow monocytes, which migrate into the target organs and mature
      into macrophages with proviral DNA transcription, but limited replication of
      virus. The MVV particles are morphologically similar to those of other
      retroviruses and the mode of replication follows the same general pattern. The
      genome organization and gene regulation resembles that of other lentiviruses. In
      addition to gag, pol and env, MVV has three auxiliary genes (tat, rev and vif),
      which seem to have similar functions as in other lentiviruses, with a possible
      exception of the tat gene. A determination of the 9200 nucleotide sequence of the
      MVV genome shows a close relationship to CAE virus, but limited sequence homology
      with other lentiviruses, and only in certain conserved domains of the reverse
      transcriptase and possibly in the surface protein. MVV infection in sheep and HIV
      1 infection in humans have a number of features in common such as a long
      preclinical period following transmission, and a slow development of multiorgan
      disease with fatal outcome. A brief early acute phase, which is terminated by the
      immune response, is also an interesting common feature. Like HIV-1, MVV is
      macrophage tropic and the early stages of the HIV-1 infection which affect the
      central nervous system and the lungs are in many ways comparable to maedi-visna.
      In contrast to HIV-1, MVV does not infect T-lymphocytes and does not cause T-cell
      depletion and immunodeficiency. This is responsible for the difference in the
      late stages of the HIV-1 and MVV infections and the final clinical outcome.
      Despite limited sequence homology, certain proteins of MVV and HIV-1 show
      structural and functional similarities. Studies of MVV may therefore help in the
      search for new drugs against lentiviruses, including HIV-1.

PMID- 16425964
TI  - Pharmacokinetic disposition of inhaled ciclesonide and its metabolite
      desisobutyryl-ciclesonide in healthy subjects and patients with asthma are
      similar.
AB  - OBJECTIVE: To evaluate whether the inflammatory process and bronchial
      constriction associated with asthma influence the pulmonary distribution and
      airway penetration of inhaled ciclesonide by investigating the pharmacokinetics
      of ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC) in
      patients with asthma and matched healthy subjects. METHODS: 12 patients with
      asthma (8 males, 4 females) and 12 healthy subjects matched for age, sex, height,
      and weight received a single inhaled dose of 1,280 microg (ex-actuator,
      equivalent to 1,600 microg ex-valve) ciclesonide by metered-dose inhaler in a
      parallel-group study. Timed blood samples were collected for measurement of serum
      concentrations of des-CIC and ciclesonide by liquid chromatography with tandem
      mass spectrometry. RESULTS: There were no differences in the pharmacokinetics of
      des-CIC between healthy subjects and patients with asthma. Ratio analysis of the
      primary variable, the area under the concentration-time curve from time 0 to
      infinity (AUC(0 - inf)) showed equivalence for des-CIC in healthy subjects and
      patients with asthma, with a ratio of 1.003 (90% confidence interval between
      0.815 and 1.234). The mean terminal half-life (t1/2) for des-CIC was also similar
      in patients with asthma (3.15 hours) and healthy subjects (3.33 hours).
      Furthermore, the pharmacokinetic parameter estimates for ciclesonide were
      comparable between the study groups. CONCLUSION: After administration of a single
      dose of ciclesonide, the pharmacokinetic parameter estimates for des-CIC were
      equivalent between patients with mild-to-moderate asthma and healthy subjects,
      suggesting that there is comparable lung deposition and activation of ciclesonide
      in the 2 populations.

PMID- 16425965
TI  - Analysis of German package inserts.
AB  - OBJECTIVE: Package inserts have an important impact on patients compliance and
      thus on the effectiveness of drug use. Despite efforts of the European or
      national regulatory authorities and manufacturers to improve the readability and
      comprehensiveness of package inserts, they are still the subject of critical
      discussion. MATERIAL AND METHODS: 68 German package inserts were chosen for a
      detailed analysis of their quality and suitability based on a set of 104 quality
      criteria developed prior to the survey. RESULTS: In many cases package inserts
      available on the German drug market did not include important information or were
      difficult to read or understand. In 73.5% of cases, the daily maximum dose was
      missing and 63.2% gave no information on the measures to take for each of the
      interactions. 66.2% of package inserts provided no instructions about the correct
      storage and 58.8% gave no instructions on the appropriate storage temperature. In
      13 cases, dosage instructions were provided only in milligrams of active
      substance instead of a number of tablets or volume of liquid. 98.5% of the 68
      package inserts included non-quantifiable statements such as "high dosage" or
      "take 2 - 4 tablets, 1 - 3 times daily". 97.1% contained repetitious information,
      83.8% included advertising elements and 8.8% contained contradictory information.
      CONCLUSION: Package inserts must be optimized and tested by selected groups of
      patients prior to approval of the drug. This will avoid misunderstandings and
      lack of information and ensure that use of the drug will give the best possible
      outcome and avoid safety risks.

PMID- 16425966
TI  - Disproportionately elevated proinsulin levels in type 2 diabetic patients treated
      with sulfonylurea.
AB  - OBJECTIVE: Hyperproinsulinemia in type 2 diabetic subjects has recently been
      accepted as an independent cardiovascular risk factor. Moreover, it has been
      confirmed that high proinsulin concentrations stimulate amylin secretion by
      pancreatic beta-cells and amyloid accumulation within pancreatic islets leading
      to impairment of pancreatic islets secretory function. The association between
      sulfonylureas administration and secretory function of pancreatic beta-cells,
      especially concerning insulin precursor peptides, is not sufficiently elucidated.
      Preliminary studies by our research group revealed that the fasting proinsulin
      serum concentration is significantly higher in type 2 diabetic patients treated
      with sulfonylureas than in a well-matched group treated with insulin only.
      METHODS: A total of 101 subjects with type 2 diabetes were treated either with
      sulfonylureas (n = 32), with insulin (n = 40), with sulfonylureas + insulin (n =
      17) or with diet alone (n = 12). RESULTS: The basal secretory function in the
      four groups were comparable (C-peptide fasting serum level > 0.5 ng/l). An effect
      of fasting glycemia, long-term metabolic control (HbA1c), postprandial
      hyperglycemia (1,5-anhydro-D-glucitol), insulin resistance (HOMA(IR)score) and
      diabetes duration on the fasting proinsulin serum level in the subjects treated
      could be excluded. CONCLUSION: The disproportionately high proinsulin levels are
      due to sulfonylureas therapy. The effect is independent of fasting glycemia, long
      term metabolic control, postprandial hyperglycemia, diabetes duration and
      peripheral insulin resistance.

PMID- 16425967
TI  - Effects of a fenofibrate/losartan combination on the plasma concentration and
      urinary excretion of purine bases.
AB  - OBJECTIVE: To assess the effects of a combination of fenofibrate and losartan on
      the plasma concentrations and urinary excretion of purine bases in healthy male
      subjects. METHODS: 5 healthy males participated in a fenofibrate plus losartan
      combination study. The plasma concentrations and urinary excretion of purine
      bases (hypoxanthine, xanthine, uric acid) were measured before and after
      administrations of losartan (100 mg o.d.) alone for 2 weeks, losartan and
      fenofibrate together for 2 weeks and fenofibrate (300 mg o.d.) alone for 2 weeks,
      which were given consecutively over a 6-week period. RESULTS: Losartan alone
      significantly reduced the serum uric acid concentration and increased uric acid
      excretion, whereas the combination of losartan and fenofibrate reduced serum uric
      acid concentrations further with a concomitant increased uric acid excretion.
      Fenofibrate alone also reduced plasma uric acid concentration with an increase in
      urinary excretion, although the effect was weak when compared with the
      combination treatment. The plasma concentrations and urinary excretion of
      oxypurines remained unchanged throughout the entire study. CONCLUSION: A
      combination of fenofibrate and losartan demonstrated an additive urate-lowering
      effect which may be beneficial in the treatment of patients with gout and
      hypertriglyceridemia.

PMID- 16425968
TI  - Methacholine challenge tests: sample sizes required in crossover trials.
AB  - OBJECTIVE: Methacholine challenge testing is common for assessing the
      pharmacodynamic properties of anti-asthma drugs. In order to design studies and
      to interpret published studies, sample size calculations are essential.
      Unfortunately, wrong sample sizes were previously reported in the literature. We
      present correct sample sizes required for the comparison of two treatments based
      on methacholine challenge testing in a crossover study. METHODS AND RESULTS:
      Formulas for sample size calculations and the resulting number of subjects
      required for a specified power are presented for studies designed to show a
      difference as well as for equivalence and non-inferiority studies. CONCLUSIONS: A
      much larger sample size is required for methacholine challenge testing than
      previously reported.

PMID- 16425969
TI  - Chronomodulated chemotherapy with oxaliplatin, 5-FU and sodium folinate in
      metastatic gastrointestinal cancer patients: original analysis of non
      hematological toxicity and patient characteristics in a pilot investigation.
AB  - OBJECTIVE: Several clinical trials have demonstrated that oxaliplatin is a useful
      agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the
      treatment of patients with colorectal carcinoma. The aims of this pilot study
      were to evaluate non-hematological toxicity and patient characteristics in
      gastrointestinal cancer patients treated with chronomodulated chemotherapy
      consisting of oxaliplatin, 5-FU and sodium folinate. METHODS: Patients with
      metastatic gastrointestinal cancer received a chronomodulated regimen with
      oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non
      hematological toxicities were evaluated and analyzed in relation to patient
      characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface
      area and smoking status. Toxicity was graded according to the National Cancer
      Institute Common Toxicity Criteria. RESULTS: The severity of non-hematological
      toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients
      with diarrhea (12.5%). The most frequent common adverse events were nausea,
      Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3
      in 11 patients (68.9%). The analyses showed that patient characteristics such as
      BMI and smoking status were associated with mucositis/stomatitis, vomiting or
      mood alteration. Furthermore, there was a relationship between smoking status and
      the overall non-hematological toxicity. Smokers had significantly higher overall
      toxicity than non-smokers and body mass index correlated significant with overall
      toxicity. CONCLUSION: The results of this pilot investigation suggest that a
      chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a
      manageable non-hematological toxicity profile and that toxicity of the
      chronomodulated schedule studied depends on the patient characteristics. In
      further investigations, risk factors determining chemotherapeutic toxicity should
      be considered. Because of the small number of patients in this pilot
      investigation, the findings need to be confirmed in a larger clinical study.

PMID- 16425971
TI  - Evaluation of prescribing errors in primary care.

PMID- 16425970
TI  - Significant food interactions observed with a nifedipine modified-release
      formulation marketed in the European Union.
AB  - The objective of this study was to compare the rate and extent of nifedipine
      bioavailability after single dose administration of Adalat OROS 30 (Reference)
      and Nifedipine Sandoz retard 30 tablets (Test). Both modified release
      formulations are marketed in Member States of the European Union. Prior to the
      clinical study the in vitro dissolution characteristics were investigated. There
      was a significant pH dependency observed with the Test product but drug release
      with the Reference product was almost independent of the experimental conditions
      used. In the subsequent open, randomized, controlled, 4-way crossover study both
      pharmaceutical products were administered to 28 healthy male volunteers, either
      after fasting overnight or immediately after a high-fat American breakfast. Blood
      sampling was performed over 48 hours post-dose for the determination of
      pharmacokinetic profiles of nifedipine. Considerable differences were observed
      between the two formulations when administered to fasted subjects where maximum
      nifedipine plasma concentration (C(max)) were higher in the case of the Test
      formulation. Differences were even more pronounced after a high-fat American
      breakfast. Under these conditions a significant food interaction was detected in
      the case of Nifedipine Sandoz retard 30 with a three-fold increase in the mean
      C(max) when compared to values obtained in fasting subjects. In contrast, food
      intake had no clinically relevant effect on bioavailability of nifedipine (rate
      and extent) in the case of Adalat OROS 30. The pharmacokinetic findings in this
      study were reflected in the adverse event pattern which indicated a potential
      tolerability problem in the case of Nifedipine Sandoz retard 30. The results
      confirm the relationship between the in vitro dissolution profile results and the
      effects of the drug in vivo. Dose dumping after intake of a high-fat meal could
      be shown. Nifedipine Sandoz retard 30 is not bioequivalent to Adalat OROS 30 and
      produced highly variable and poorly predictable nifedipine plasma concentrations.
      The differences observed between the two products investigated may have direct
      therapeutic relevance when switching from one formulation to the other and, in
      particular, when administration conditions change i.e. administration in the
      fasting state and administration with a meal, since the pharmacological and
      therapeutic actions of nifedipine are closely associated with the concentration.

PMID- 16425973
TI  - Calcipotriol-betamethasone ointment versus calcipotriol ointment in the treatment
      of psoriasis vulgaris.
AB  - Of 17 patients (10 men and 7 women) with psoriasis vulgaris, aged between 12 and
      59 years, included in this study, 4 patients were excluded (3 because of a
      treatment follow-up irregularity and 1 due to severe irritation). Thirteen
      patients completed the 6-week treatment course where each patient was instructed
      to apply calcipotriol-betamethasone ointment on the right side and calcipotriol
      ointment on the left side. The treatment effect was assessed according to the
      psoriasis area severity index (PASI) changes, and complete blood count and serum
      calcium was done prior to and at the end of the treatment. Results showed that
      both sides had improved by 92.3%, with a marked reduction in the mean PASI (from
      11.5 to 2.2); a better reduction was observed in the right side during the second
      and third visits. A marked improvement to complete clearance was seen in 84.6% in
      calcipotriol-betamethasone side and 76.9% in calcipotriol alone. Mild irritation
      was reported in the left side in 15.4% which was tolerated with the continuation
      of treatment application. No telangiectasia or atrophy was observed on the right
      side. In conclusion, calcipotriol-betamethasone may be recommended in the early
      weeks of the treatment of psoriasis vulgaris, and it is helpful in psoriasis
      patients with irritation to calcipotriol alone.

PMID- 16425972
TI  - Calcipotriol monotherapy versus calcipotriol plus UVA1 versus calcipotriol plus
      narrow-band UVB in the treatment of psoriasis.
AB  - The purpose of this study was to evaluate the efficacy of calcipotriol ointment
      as monotherapy versus calcipotriol in combination with narrow-band ultraviolet
      (UV)-B or UVA1 phototherapy and to determine whether calcipotriol in combination
      with UVA1 is an alternative to calcipotriol with narrow-band UVB phototherapy.
      Forty-five patients with plaque psoriasis were divided into three treatment
      groups with no significant differences in Psoriasis Area and Severity Index
      (PASI) scores, mean age, sex or skin type. The total duration of the treatment
      was 3 months. Regarding PASI score, psoriasis regression was statistically
      significant between the groups. The response to UVA1 and narrow band UVB with
      calcipotriol was superior to calcipotriol monotherapy. UVA1 phototherapy with
      calcipotriol could be an alternative to narrow-band UVB phototherapy with
      calcipotriol.

PMID- 16425974
TI  - Comparison of the effects of D-003, a mixture of high-molecular-weight aliphatic
      acids from sugarcane wax, and pravastatin on bones and osteoclast apoptosis of
      ovariectomized rats.
AB  - The mevalonate pathway is relevant in bone cells. Statins inhibit 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme of this route,
      stimulating osteoblast differentiation and activity. Pravastatin increases bone
      formation markers in postmenopausal women and bone density in diabetics. D-003 is
      a mixture of high-molecular-weight acids purified from sugarcane wax which
      inhibits cholesterol biosynthesis through HMG-CoA reductase regulation,
      preventing bone loss in osteoporosis induced with ovariectomy and prednisolone in
      rats. We investigated the effects of D-003 (50 mg/kg) and pravastatin (20 mg/kg)
      orally administered for 12 weeks to ovariectomized rats. Female rats were
      randomized in four groups (10 rats/group): two control groups treated with the
      vehicle, one false-operated (sham) and another ovariectomized (positive control),
      while two other groups received D-003 or pravastatin. Bone resorption and
      formation was studied through histomorphometry and apoptosis through
      immunohistochemistry. D-003 and pravastatin significantly (p < 0.001) prevented
      the changes of trabecular bone versus ovariectomized rats and (p < 0.001) the
      increase of the surface and number of osteoclasts versus ovariectomized controls.
      D-003 and pravastatin, however, did not modify osteoblast surfaces, a bone
      formation marker D-003 and pravastatin increased osteoclast apoptosis and reduced
      (p < 0.05) osteoblast and osteocyte apoptosis versus ovariectomized controls; D
      003 was more effective (p < 0.05) than pravastatin. In conclusion, D-003 (50
      mg/kg) orally administered for 12 weeks prevented bone loss and bone resorption
      in ovariectomized rats, increasing osteoclast apoptosis. The preventive effects
      of D-003 on bone loss and resorption in ovariectomized rats are comparable to
      those of pravastatin. Both drugs inhibited osteoblast apoptosis but failed to
      change osteoblast surface. The effects of D-003 on bone cell apoptosis were
      greater than those of pravastatin. Therefore, D-003 could be used to prevent or
      treat bone loss in postmenopausal women, but further animal studies and clinical
      trials are required to confirm the clinical relevance of this potential effect.

PMID- 16425975
TI  - Therapeutic effect of D-004, a lipid extract from Roystonea regia fruits, on
      prostate hyperplasia induced in rats.
AB  - Benign prostatic hyperplasia (BPH) is a nonmalignant growth of prostate leading
      to difficulty in urinating. Drug therapy, phytotherapy included, is frequently
      used to treat BPH. D-004 is a lipid extract from Roystonea regia fruits, and
      previous studies have shown that oral treatment with D-004 for 14 days prevented
      prostate hyperplasia (PH) induced by testosterone in rats. No information is
      available, however; about the effects of D-004 in reverting already established
      PH. This study investigated whether D-004 could improve PH after oral dosing with
      testosterone in rats. Rats were distributed in five groups (10 rats/group). One
      group was injected with soy oil (negative control) and four groups were injected
      with testosterone: one was orally treated with the vehicle (positive control),
      two with D-004 (200 and 400 mg/kg) and the other with Saw palmetto (400 mg/kg).
      At study completion, the rats were sacrificed and the prostates were removed and
      weighed. D-004 (200 and 400 mg/kg) significantly and dose-dependently decreased
      prostate enlargement by 85% and 98%, respectively, versus the positive control.
      Likewise, Saw palmetto (400 mg/kg) significantly reduced prostate weight by 73%
      versus the positive control. D-004 (400 mg/kg) was more effective (p < 0.05) than
      Saw palmetto (400 mg/kg) in lowering prostate enlargement. D-004 and Saw palmetto
      also decreased the prostate weight to body weight ratio, but did not affect body
      weight. In conclusion, D-004 (200 and 400 mg/kg) orally administered was
      effective for reducing PH after testosterone dosing. D-004 (400 mg/kg) was more
      effective than Saw palmetto (400 mg/kg). Further studies, however, are needed to
      corroborate the present results.

PMID- 16425976
TI  - Does mycophenolate mofetil increase the incidence of infections in renal
      transplant recipients?
AB  - The aim of this study was to investigate infectious complications in renal
      transplant recipients (RTRs) receiving mycophenolate mofetil (MMF) for prevention
      of acute transplant rejection. A group of RTRs (n = 47) receiving 1.0-2.0 g/day
      of MMF with cyclosporine A (CsA) and prednisolone to maintain immunosuppression
      was compared with a group (n = 47) taking triple immunosuppressive therapy
      including azathioprine. In both groups the etiology and incidence of infections
      were evaluated. During 2 years post-transplant, various infections developed in
      72.3% of patients who received MMF and in 93.6% of those who received
      azathioprine. The incidence of viral infections was 53.2% in the MMF group and
      59.6% in the azathioprine group and the incidence of bacterial infection was
      55.3% and 70.2%, respectively There were two cases of active tuberculosis in the
      azathioprine group and one in the MMF group. MMF 1.0-2.0 g/day does not increase
      infection rates in RTRs compared with azathioprine.

PMID- 16425977
TI  - Induction of mononuclear cell infiltration into liver by Japanese herbal
      medicine.
AB  - Juzen-Taiho-To (JTT) is a Japanese herbal medicine that has been administered
      mainly to patients weakened by long illness. Currently, it has also been used for
      cancer patients and showed antitumor effects that have been reported as
      phagocytosis enhancement, cytokine induction and antibody production. In this
      study, we examined the effect of oral administration of JTT in mice on the
      immunological restoration of the liver, especially focused on natural killer (NK)
      T-cell induction. Mice were grouped to receive JTT or placebo orally for a period
      of 1, 3 and 7 days. After sacrifice, the liver tissue was fixed, embedded and
      stained with hematoxylineosin and some antibodies by common staining methods.
      Transmission electron microscope (TEM) observation was also carried out. Although
      the JTT-treated mice had the same appearance as the non-JTT-treated mice, their
      livers were infiltrated by massive mononuclear cells, some of which were
      aggregated in clusters. Immunohistochemical staining revealed that there was
      abundant cytokine expression of interleukin (IL)-12 and massive infiltration of
      mononuclear cells with large granules in the liver of JTT-treated mice. Oral
      administration of JTT may induce the expression of IL-12 and be followed by
      immunological restoration such as NK T-cell induction in liver

PMID- 16425978
TI  - Azelnidipine, a dihydropyridine-based calcium antagonist, inhibits angiotensin II
      induced oxidative stress generation and downregulation of pigment epithelium
      derived factor mRNA levels in microvascular endothelial cells.
AB  - We have previously shown that azelnidipine, a long-acting dihydropyridine-based
      calcium antagonist (DHP), inhibited tumor necrosis factor-alpha-induced
      endothelial cell (EC) activation through its antioxidative properties. However
      whether azelnidipine could also block the angiotensin II (Ang II)-signaling in
      ECs remains to be elucidated. Since Ang II-type 1 receptor interaction could
      contribute to exacerbation of diabetic retinopathy by downregulating pigment
      epithelium-derived factor (PEDF) gene expression in ECs, we examined here whether
      azelnidipine inhibited the Ang II-induced reactive oxygen species (ROS)
      generation and subsequent PEDF gene suppression in microvascular ECs.
      Azelnidipine, but not nitrendipine, the other popular DHFP completely inhibited
      the Ang II-induced ROS generation in ECs. Furthermore, azelnidipine, but not
      nitrendipine, was found to partially restore decreased PEDF mRNA levels in Ang II
      exposed ECs. The present study suggests that azelnidipine could inhibit the Ang
      II-induced decrease in PEDF mRNA levels in ECs through its antioxidative
      properties. Upregulation of PEDF by azelnidipine may become a therapeutic target
      for the treatment of diabetic retinopathy associated with hypertension.

PMID- 16425979
TI  - Blockade by nifedipine of advanced glycation end product-induced CD40-CD40 ligand
      interaction in endothelial cells.
AB  - Advanced glycation end products (AGEs), the senescent macroprotein derivatives
      that form in increased amounts in diabetes, have been implicated in the
      pathogenesis of accelerated atherosclerosis. There is a growing body of evidence
      that CD40-CD40 ligand (CD40L) interaction also plays an important role in
      atherogenesis. However, the effects of AGEs on CD40-CD40L signaling in
      endothelial cells (ECs) remain to be elucidated. In this study, we investigated
      (i) whether injection of AGE-proteins to normal rats stimulates CD40L expression
      on circulating platelets and (ii) whether AGEs up-regulate CD40 mRNA levels in
      cultured ECs. We further examined the effects of nifedipine, one of the most
      popular dihydropyridine-based calcium antagonists, on CD40 gene expression in AGE
      exposed ECs. Platelet surface CD40L expression was increased in AGE-bovine serum
      albumin (AGE-BSA)-injected rats, compared with nonglycated BSA administration.
      AGEs were found to induce up-regulation of CD40 mRNA levels in ECs, which were
      significantly blocked by nifedipine. These results suggest that AGEs could
      enhance CD40-CD40L interaction, thereby promoting atherosclerosis in diabetes.
      Blockade of CD40-CD40L signaling in ECs may be a molecular target for the
      vasculoprotective property of nifedipine.

PMID- 16425980
TI  - Inhibition by advanced glycation end products (AGEs) of pigment epithelium
      derived factor (PEDF) gene expression in microvascular endothelial cells.
AB  - Pigment epithelium-derived factor (PEDF) is a natural extracellular component of
      the retina with neuronal differentiating activity. Recently, decreased levels of
      PEDF in the mammalian eye have been shown to participate in the pathogenesis of
      diabetic retinopathy In addition, advanced glycation end products (AGEs),
      senescent macroprotein derivatives that form at an accelerated rate under
      diabetes, have also been implicated in the development and progression of
      diabetic retinopathy. However the role of AGEs in decreased levels of PEDF in the
      eye remains to be elucidated. In this study, we examined the effects of AGEs on
      PEDF gene expression in microvascular endothelial cells (ECs). Various types of
      immunochemically distinct AGEs, which were prepared in vitro by incubating bovine
      serum albumin with glucose, glyceraldehyde or glycolaldehyde, significantly
      decreased endothelial mRNA levels of PEDF Furthermore, H2O2 dose-dependently
      suppressed PEDF gene expression in ECs. Our present results suggest that AGEs
      could down-regulate mRNA levels of PEDF in ECs, probably via oxidative stress
      generation. The deleterious effects of AGEs on diabetic retinopathy could be due,
      at least in part, to their PEDF-inhibitory properties.

PMID- 16425982
TI  - Renal cell carcinoma: a new era?

PMID- 16425983
TI  - Highlights from the International Conference on Molecular Targets and Cancer
      Therapeutics: Discovery, Biology, And Clinical Applications, Philadelphia, PA,
      November 2005; ECCO 13--The European Cancer Conference, Paris, France, October 30
      November 3, 2005.

PMID- 16425984
TI  - Perioperative complications of radical retropubic prostatectomy.
AB  - The opinions and assertions contained herein are the private views of the authors
      and are not to be construed as reflective of the views of the US Army or the
      Department of Defense. Radical retropubic prostatectomy has long been considered
      one of the most difficult procedures in the urologist's armamentarium. Therefore,
      we performed a thorough review of recent literature regarding intraoperative and
      postoperative complications. The intent of this effort is to review established
      data regarding the most frequently seen complications and to highlight recent
      developments regarding the prevention or treatment of such complications.

PMID- 16425985
TI  - SU11248 and AG013736: current data and future trials in renal cell carcinoma.
AB  - Several molecular pathways are implicated in renal cell carcinoma (RCC)
      pathogenesis, including the von Hippel-Lindau gene inactivation leading to
      vascular endothelial growth factor (VEGF) and platelet derived growth factor
      (PDGF) expression. SU11248 and AG013736 are small-molecule inhibitors of the
      tyrosine kinase portion of the VEGF and PDGF receptors. Substantial clinical
      activity has been reported for these agents in metastatic RCC trials, leading to
      additional investigations in a variety of settings.

PMID- 16425987
TI  - Prostate cancer therapy with high-intensity focused ultrasound.
AB  - High-intensity focused ultrasound (HIFU) has been used to ablate benign and
      malignant prostate tissue for several decades. This review summarizes the
      technology and available clinical trials to date. Continued technological
      advances combined with well-designed clinical trials could allow HIFU to become
      part of the arsenal against prostate cancer.

PMID- 16425986
TI  - Cytokine therapy: a standard of care for metastatic renal cell carcinoma?
AB  - Metastatic renal cell carcinoma (RCC) is refractory to standard cytotoxic
      chemotherapy regimens. The rationale for the use of cytokines in RCC is based on
      compelling evidence that RCC is sensitive to immunologic manipulation. Cytokine
      based therapy with interleukin-2 (IL-2) or interferon (IFN)-alpha can result in
      objective tumor responses in as many as 15% of patients, and in selected
      patients, these responses can be durable. The development of targeted therapies
      for clear-cell RCC with the potential for greater antitumor activity and less
      toxicity has brought into question the role of cytokines in this patient
      population. However, no noncytokine therapy to date has proven curative in
      patients with metastatic RCC. Until results from ongoing trials clearly
      demonstrate superiority of newer agents over IFN-alpha or IL-2, these agents
      should remain a standard of care for the treatment of RCC.

PMID- 16425988
TI  - What constitutes high-risk locally advanced prostate cancer?
AB  - Excluding basal and squamous cell cancers of the skin, prostate cancer is the
      most common malignancy diagnosed in the United States. With increasing awareness
      and routine prostate-specific antigen testing, a remarkable migration in the
      clinical presentation of the disease has occurred in the past 20 years. An
      increasingly greater proportion of men are diagnosed with clinically organ
      confined disease. In parallel, the incidence of men presenting with clinically
      bulky locoregional or metastatic disease has decreased. Despite the stage
      migration, when clinical and pathologic parameters are taken into account, a
      significant number of men with clinically localized prostate cancer do not have
      truly organ-confined disease. Such men might not to be cured with single
      modality, locally directed therapies. Thus, prostate cancer represents a disease
      spectrum with a number of biologic and clinical factors determining disease
      extent. An overview of some of these aspects of the disease is presented.

PMID- 16425989
TI  - Antiangiogenesis: a possible treatment option for prostate cancer?
AB  - With a need for effective treatment modalities in prostate cancer, angiogenesis
      is a likely target for the interference of tumor progression. Angiogenesis
      promotes the vasculature of a tumor, allowing for tumor progression and for
      cancer cells to metastasize and spread throughout the circulatory system. To
      date, there are > 20 antiangiogenic drugs undergoing preclinical and clinical
      investigation alone and in conjunction with other treatment options to determine
      the validity of antiangiogenic agents in the treatment of prostate cancer. This
      article reviews several aspects of antiangiogenesis and its relationship to the
      treatment of prostate cancer.

PMID- 16425990
TI  - Cyclooxygenase-2: a therapeutic target for prostate cancer.
AB  - The discovery and elucidation of prostaglandin (PG) pathways, particularly the
      molecular and clinical role of cyclooxygenase-2 (COX-2) function, has been found
      to have an important role in neoplasia. Current understanding of the role of COX
      2 activity and therefore the potential clinical usefulness of COX-2-specific
      inhibitors in prostate cancer will be discussed herein. The discovery of PG
      pathways, the molecular and clinical roles of COX-2 function, and the
      corresponding application to neoplasia were reviewed in the scientific literature
      from 1960 through the present time. In addition, thorough review of recent
      abstract presentations at scientific meetings (American Urological Association
      and American Society of Clinical Oncology annual meetings from 1998 to the
      present) was undertaken regarding the potential role of COX-2 in urologic
      cancers. Reduced apoptosis, increased angiogenesis, and immunosuppression are
      just some of the known sequelae of COX-2 overexpression, and each effect could
      have an important role in tumor formation and progression. Preclinical research
      and pilot clinical studies in prostate cancer to date have been promising. We are
      just beginning to understand the molecular mechanisms and clinical effects of COX
      2 function and its inhibition and the potential for COX-2-specific inhibitors to
      affect tumor biology and growth, and thereby serve as antitumor drugs in
      therapeutic and chemopreventive roles in prostate cancer. The absence of complete
      scientific understanding in these areas presents an exciting opportunity for
      innovative and important scientific study.

PMID- 16425991
TI  - Radiation Therapy Oncology Group 0521: a phase III randomized trial of androgen
      suppression and radiation therapy versus androgen suppression and radiation
      therapy followed by chemotherapy with docetaxel/prednisone for localized, high
      risk prostate cancer.

PMID- 16425992
TI  - A phase I study of a DNA vaccine targeting prostatic Acid phosphatase in patients
      with stage D0 prostate cancer.

PMID- 16425993
TI  - Sorafenib: scientific rationales for single-agent and combination therapy in
      clear-cell renal cell carcinoma.
AB  - Clear-cell renal cell carcinoma (RCC) is characterized by the loss of von Hippel
      Lindau disease protein and the resultant dysregulation of the vascular
      endothelial growth factor (VEGF)/VEGF receptor (VEGFR), platelet-derived growth
      factor-beta (PDGF-beta)/PDGF receptor-beta (PDGFR-beta), and transforming growth
      factor-alpha (TGF-alpha)/epidermal growth factor receptor (EGFR)/Raf pathways,
      which contribute to angiogenesis, lymphangiogenesis, and tumor cell growth and
      survival. Significant advances in the treatment of clear-cell RCC have been
      derived from agents that target these pathways, including the multiple-kinase
      inhibitors (MKIs) sorafenib, sunitinib, and AG013736, which target multiple
      VEGFRs as well as PDGFR-beta. Sorafenib has the added advantage of inhibiting
      multiple different Raf isoforms, which enables it to target TGF-alpha/EGFR
      signaling and may also enhance its inhibition of VEGFR and PDGFR-beta. This
      review will examine the recent advances in our understanding of the biology of
      clear-cell RCC and show how those advances have helped delineate new targets of
      opportunity for treatment. It will also present the early clinical results of
      agents that target the pathways dysregulated in clear-cell RCC, with special
      emphasis on sorafenib and the other active MKIs, and will describe the scientific
      rationales for ongoing and future sorafenib-based combination therapy trials in
      RCC.

PMID- 16425995
TI  - Interleukin-6 promotes anti-OspA borreliacidal antibody production in vitro.
AB  - Determination of the immunological mediators responsible for promoting the
      production of borreliacidal antibody may facilitate the development of an
      improved borreliosis vaccine for human and veterinary use. Previously, we
      developed an in vitro assay to determine if borreliacidal antibody production
      could be augmented by treatment with different cytokines. In this study, in vitro
      treatment of lymph node cells producing borreliacidal antibody with recombinant
      interleukin-6 (rIL-6) resulted in a fourfold enhancement of anti-OspA
      borreliacidal antibody. Moreover, rIL-6 enhanced Western immunoblot titers and
      increased the number of B lymphocytes. In contrast, treatment of anti-OspA
      borreliacidal antibody-producing cells with anti-IL-6 resulted in a fourfold
      reduction in borreliacidal activity. Treatment with anti-IL-6 also inhibited
      enhanced borreliacidal antibody production induced by anti-gamma interferon.
      These data suggest that IL-6 plays a significant role in the production of anti
      OspA borreliacidal antibodies.

PMID- 16425996
TI  - Cellular immune responses in asymptomatic human immunodeficiency virus type 1
      (HIV-1) infection and effects of vaccination with recombinant envelope
      glycoprotein of HIV-1.
AB  - Effects of human immunodeficiency virus type 1 (HIV-1) recombinant envelope
      glycoprotein vaccines on cell-mediated immune (CMI) responses were assessed in
      HIV-1-infected patients. Asymptomatic, antiretroviral-treatment-naive, HIV-1
      infected patients with CD4(+) T-cell counts greater than 400/microl received
      multiple intramuscular injections of HIV-1 IIIB recombinant envelope glycoprotein
      (rgp160) vaccine or HIV-1 MN recombinant envelope glycoprotein (rgp120) vaccine
      (eight patients, referred to as the HIV-1 vaccinees) or placebo or hepatitis B
      vaccine (three patients, referred to as the controls). Lymphocyte proliferation
      in response to HIV-1 envelope glycoproteins, both homologous and heterologous to
      the HIV-1 immunogens, was absent prior to study treatment in all patients but
      increased significantly during the vaccination series and after the final
      vaccination in HIV-1 vaccinees (P < 0.05) and remained absent in control
      patients. In flow cytometric analyses of intracellular cytokines, T-cell receptor
      stimulation with an anti-CD3 antibody induced gamma interferon (IFN-gamma)
      expression by activated CD4(+) and CD8(+) lymphocytes at greater frequencies than
      did stimulation with recombinant envelope glycoprotein and p24 of HIV-1 (P <
      0.05). Mean frequencies of HIV-1 envelope glycoprotein-stimulated, activated
      intra-cellular IFN-gamma-producing CD4(+) and CD8(+) lymphocytes and of
      interleukin-2-producing CD4(+) lymphocytes did not increase after vaccination,
      but cytokine-producing cells were detectable in some patients. Comparing pre- to
      post-HIV-1 vaccination time points, changes in frequencies of activated, IFN
      gamma-producing CD4(+) cells correlated inversely with changes in lymphocyte
      proliferation in response to recombinant envelope glycoprotein in HIV-1 vaccinees
      (P < 0.05). Increased CMI responses to HIV-1 envelope glycoprotein measured by
      lymphocyte proliferation were associated with HIV-1 recombinant envelope
      glycoprotein vaccines.

PMID- 16425997
TI  - Immunoglobulin G avidity in differentiation between early and late antibody
      responses to West Nile virus.
AB  - In 1999 West Nile virus (WNV) surfaced in the United States in the city of New
      York and spread over successive summers to most of the continental United States,
      Canada, and Mexico. Because WNV immunoglobulin M (IgM) antibodies have been shown
      to persist for up to 1 year, residents in areas of endemicity can have persistent
      WNV IgM antibodies that are unrelated to a current illness with which they
      present. We present data on the use of IgG avidity testing for the resolution of
      conflicting data arising from the testing of serum or plasma for antibodies to
      WNV. Thirteen seroconversion panels, each consisting of a minimum of four
      samples, were used. All samples were tested for the presence of WNV IgM and IgG
      antibodies, and the avidity index for the WNV IgG-positive samples was
      calculated. Panels that exhibited a rise in the WNV IgM level followed by a
      sequential rise in the WNV IgG level were designated "primary." Panels that
      exhibited a marked rise in the WNV IgG level followed by a sequential weak WNV
      IgM response and that had serological evidence of a prior flavivirus infection
      were designated "secondary." All samples from the "primary" panels exhibited low
      avidity indices (less than 40%) for the first 20 to 30 days after the recovery of
      the index sample (the sample found to be virus positive). All of the "secondary"
      samples had elevated WNV IgG levels with avidity indices of > or =55%, regardless
      of the number of days since the recovery of the index sample. These data
      demonstrate that it is possible to differentiate between recent and past exposure
      to WNV or another flavivirus through the measurement of WNV IgG avidity indices.

PMID- 16425998
TI  - Diagnostic implications of antigen-induced gamma interferon production by blood
      leukocytes from Mycobacterium bovis-infected reindeer (Rangifer tarandus).
AB  - The only approved method of tuberculosis (TB) surveillance of reindeer within the
      United States is tuberculin skin testing; however, skin testing has an apparent
      lack of specificity, since numerous reindeer are classified as reactors, yet
      Mycobacterium bovis is not isolated from tissues upon necropsy. The objective of
      this study was to evaluate the ability of an in vitro assay (the Cervigam assay)
      to detect gamma interferon (IFN-gamma) produced by blood leukocytes in response
      to mycobacterial antigens from M. bovis-infected reindeer. Thirteen male reindeer
      approximately 9 months of age were inoculated with 10(5) CFU M. bovis in their
      tonsillar crypts. Stimulation of whole-blood cultures with a mitogen resulted in
      significant production of IFN-gamma compared to that by nonstimulated samples.
      Responses by infected reindeer to M. bovis purified protein derivative (PPD) were
      as much as 3.5-fold higher than those by noninfected reindeer (n = 4). Despite
      differences in responses to PPD by the two groups, reindeer within the
      noninfected group had responses of >0.1 change in optical density (DeltaOD) (a
      level generally considered positive) to PPD. Mean responses by infected reindeer
      to a rESAT-6-CFP-10 fusion protein (Mycobacterium tuberculosis complex specific)
      were as much as 20-fold higher than respective responses by noninfected reindeer
      at all time points. Additionally, responses by 3/4 noninfected reindeer were <0.1
      DeltaOD (considered negative) at each time point. To further evaluate the
      specificity of the assay, samples were collected from reindeer in a TB-free herd.
      All reindeer had responses to mitogen; however, only 1 of 38 had a response to
      PPD, and none of the reindeer responded to rESAT-6-CFP-10. Together, these
      findings indicate that IFN-gamma-based tests may prove useful for TB surveillance
      of reindeer.

PMID- 16425999
TI  - Simultaneous detection of antibodies to six nonhuman-primate viruses by multiplex
      microbead immunoassay.
AB  - To maintain healthy nonhuman primates for use in biomedical research, animals are
      routinely screened for several infectious agents at most facilities. Commonly,
      monkey serum samples are tested by conventional immunoassays, such as enzyme
      linked immunosorbent assays (ELISAs) or Western blotting, for antibodies to
      specific infectious agents. For testing for antibodies against multiple agents in
      each sample, conventional immunoassays are laborious and time-consuming. More
      efficient immunoassays are needed. Accordingly, we have developed a novel
      multiplex serodiagnostic system based on individually identifiable, fluorescent
      microbead sets, where each bead set is coated with antigens from a purified
      preparation of a specific virus. The coated bead sets are mixed to enable the
      detection of antibodies to multiple viruses in one serum or plasma sample. These
      viruses include four agents that are routinely tested for maintenance of specific
      pathogen-free monkeys, namely, simian immunodeficiency virus, simian type D
      retrovirus, simian T-cell lymphotropic virus, and herpes B virus, as well as
      simian foamy virus and rhesus cytomegalovirus, both of which are commonly found
      in nonhuman primates. This multiplex microbead immunoassay (MMIA) enabled the
      simultaneous detection of antibodies to all six viruses in single serum samples
      as small as 1 microliter. The results obtained by MMIA analysis correlated with
      results of conventional ELISAs, which detect antibodies to single agents. Thus,
      this multiplex microbead detection system is an efficient diagnostic modality for
      serosurveillance of nonhuman primates.

PMID- 16426000
TI  - Comparison of a new ESAT-6/CFP-10 peptide-based gamma interferon assay and a
      tuberculin skin test for tuberculosis screening in a moderate-risk population.
AB  - Screening for latent tuberculosis infection (LTBI) with Mantoux tuberculin skin
      test (TST) has many limitations, including false-positive results due to exposure
      to Mycobacterium other than tuberculosis (TB) and BCG vaccination. A total of 474
      adult inmates in a county jail were screened for LTBI using TST and a new ESAT
      6/CFP-10 peptide-based whole-blood gamma interferon (IFN-gamma) assay. LTBI
      prevalence was 9.0 and 5.4% as determined by TST and IFN-gamma assay,
      respectively. Overall, agreement between test results was 90% (kappa = 0.25).
      Positive TST results were significantly associated with increased age (odds ratio
      [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.08), African-American
      ethnicity (OR, 4.97; 95% CI, 1.58 to 15.68), foreign birth (OR, 20.20; 95% CI,
      4.21 to 97.02) and prior incarceration (OR, 6.19; 95% CI, 1.48 to 25.95).
      Positive IFN-gamma assay results were significantly associated with African
      American ethnicity (OR, 5.58; 95% CI, 1.16 to 26.74). Factors associated with
      statistically significant discordance between TST and IFN-gamma assay results
      were African-American ethnicity (OR, 0.29; 95% CI, 0.11 to 0.77), foreign birth
      (OR, 0.23; 95% CI, 0.07-0.80), and prior incarceration (OR, 0.06; 95% CI, 0.01
      0.50). Among subjects born in the United States, African-American ethnicity was
      the only variable significantly associated with positive test results for both
      TST (OR, 4.26; 95% CI, 1.38 to 13.16) and IFN-gamma assay (OR, 5.74; 95% CI, 1.19
      to 27.75) and remained associated with statistically significant discordance
      between TST and IFN-gamma assay results. The reactivity of the new IFN-gamma
      assay is unaffected by prior BCG vaccination or serial TSTs but may be diminished
      in African-Americans. Future longitudinal studies are needed to assess the
      sensitivity and specificity of this new assay in detecting LTBI.

PMID- 16426001
TI  - Recombinant multiepitope protein for early detection of dengue infections.
AB  - Dengue fever is a mosquito-borne viral disease prevalent mainly in tropical
      countries. As the clinical manifestations of dengue are not very unique,
      laboratory diagnosis is crucial in identifying cases of dengue infection.
      Detection of dengue infection based on the identification of antidengue
      antibodies has emerged as a practical and reliable means of diagnosing dengue
      fever. We recently developed a customized recombinant dengue multiepitope protein
      (r-DME-G) that can specifically detect the immunoglobulin G (IgG) class of
      antidengue antibodies in patient sera. Using this strategy, we have now created
      another dengue multiepitope protein, r-DME-M, with specificity for the IgM class
      of antidengue antibodies. A synthetic gene encoding the r-DME-M protein was
      expressed as a maltose-binding protein fusion in Escherichia coli. The
      recombinant protein was purified in a single affinity chromatographic step to
      obtain yields of approximately 15 mg purified protein/liter of culture. The
      purified protein was used to develop an in-house IgM enzyme-linked immunosorbent
      assay (ELISA) and tested using a panel of 172 patient sera characterized using
      the commercially available Dengue Duo rapid strip test from PanBio, Australia.
      The IgM ELISA results showed that the r-DME-M protein not only recognized all
      IgM(+) samples identified by the PanBio test but also identified samples missed
      by the latter test. We also successfully adapted the r-DME-M protein to a rapid
      strip test format. This approach of creating customized antigens coupled to
      overexpression in E. coli and simple purification offers a promising alternative
      option to dengue diagnosis with the potential to circumvent the drawbacks of the
      whole virus antigen-based commercial kits.

PMID- 16426002
TI  - Development of a clinical assay to evaluate toll-like receptor function.
AB  - Toll-like receptors (TLRS) recognize pathogen-associated molecular patterns to
      enable innate immune responses. A number of genetic defects influencing the
      function of these receptors have been identified and are associated with
      recurrent and/or severe infection. Our goal was to develop a reproducible assay
      of TLR function in order to evaluate patients with recurrent infection who would
      be suspected of having a genetic defect affecting TLR signaling. We chose to
      study peripheral blood mononuclear cells (PBMCS) to avoid potential influences of
      soluble factors contained in whole blood, and we utilized ligands for TLRS 1/2,
      2/6, 3, 4, 5, 6, 7, and 9. Tumor necrosis factor (TNF) production in PBMC
      supernatants was measured by an enzyme-linked immunosorbent assay after TLR
      ligand stimulation and was dependent on gene transcription and NF-kappaB
      activation. Some variables affecting the assay were assessed, including the
      effects of: blood anticoagulant, serum-containing media, incubation time, ligand
      storage, blood storage time, and cell cryopreservation. By using optimized assay
      conditions, effective concentrations of individual ligands and mean responses to
      those ligands were established for healthy control donors. Finally, three
      patients with a mutation in the IKBKG gene, encoding the NF-kappaB essential
      modulator (NEMO) protein, were evaluated as disease controls and were almost
      uniformly below the standard deviation of healthy donors for all ligands tested.
      Although a number of variables influence TLR ligand-induced TNF responses, this
      assay can be optimized for potential clinical use to screen patients with primary
      immunodeficiencies affecting TLR function.

PMID- 16426003
TI  - International multicenter evaluation of autoantibodies to ribosomal P proteins.
AB  - Autoantibodies to the ribosomal phosphoproteins (Rib-P) are a serological feature
      of patients with systemic lupus erythematosus (SLE). The reported prevalence of
      anti-Rib-P antibodies in SLE ranges from 10 to 40%, being higher in Asian
      patients. The variation in the observed frequency may be related to a number of
      factors but is dependent in large part on the test system used to detect the
      autoantibodies. An association of anti-Rib-P with central nervous system
      involvement and neuropsychiatric manifestations of SLE has been controversial. In
      the present international multicenter study, we evaluated the clinical accuracy
      of a new sensitive Rib-P-specific enzyme-linked immunosorbent assay based on
      recombinant Rib-P polypeptides. The results showed that 21.3% of 947 SLE
      patients, but only 0.7% of 1,113 control patients, had a positive test result (P
      < 0.0001). The sensitivity, specificity, positive and negative predictive values,
      and diagnostic efficiency were determined to be 21.3%, 99.3%, 95.6%, 62.2%, and
      65.3%, respectively. When evaluated in the context of participating centers, the
      prevalence of anti-Rib-P antibodies was found in descending frequency, as
      follows: China (35%) > Poland (34%) > Japan (28%) > United States (26%) > Germany
      (Freiburg; 23.3%) > Denmark (20.5%) > Germany (Berlin; 19%) > Mexico (15.7%) >
      Israel (11.7%) > Brazil (10%) > Canada (8%). The substantial data from this study
      indicate that the prevalence of anti-Rib-P antibodies may not be restricted to
      the genetic background of the patients or to the detection system but may depend
      on regional practice differences and patient selection. We confirm previously
      reported associations of antiribosomal antibodies with clinical symptoms and
      serological findings. Remarkably, we found a lower occurrence of serositis in Rib
      P-positive lupus patients.

PMID- 16426004
TI  - Detection of immunoglobulin G antibodies to Neospora caninum in humans: high
      seropositivity rates in patients who are infected by human immunodeficiency virus
      or have neurological disorders.
AB  - Considering that little is known about the epidemiology of Neospora caninum
      infection in humans, particularly in populations with high Toxoplasma gondii
      infection rates, the present study aimed to investigate the presence of
      antibodies to N. caninum in T. gondii-seropositive and -seronegative individuals.
      A total of 256 serum samples divided into four groups (61 samples from human
      immunodeficiency virus [HIV]-positive patients, 50 samples from patients with
      neurological disorders, 91 samples from newborns, and 54 samples from healthy
      subjects) were assessed for N. caninum and T. gondii serologies by indirect
      fluorescent-antibody test, enzyme-linked immunosorbent assay, and immunoblotting
      (IB). Immunoglobulin G antibodies to N. caninum were predominantly detected in
      HIV-infected patients (38%) and patients with neurological disorders (18%), while
      newborns and healthy subjects showed lower seropositivity rates (5% and 6%,
      respectively). Seropositivity to N. caninum was significantly associated with
      seropositivity to T. gondii in both HIV-infected patients and patients with
      neurological disorders. Seroreactivity to N. caninum was confirmed by IB, with
      positive sera predominantly recognizing the 29-kDa antigen of N. caninum. The
      results of this study indicate the presence of N. caninum infection or exposure
      in humans, particularly in HIV-infected patients or patients with neurological
      disorders, who could have opportunistic and concurrent infections with T. gondii.
      These findings may bring a new concern for the unstable clinical health of HIV
      infected patients and the actual role of N. caninum infection in
      immunocompromised patients.

PMID- 16426005
TI  - Antigen mining with iterative genome screens identifies novel diagnostics for the
      Mycobacterium tuberculosis complex.
AB  - The definition of antigens for the diagnosis of human and bovine tuberculosis is
      a research priority. If diagnosis is to be used alongside Mycobacterium bovis BCG
      based vaccination regimens, it will be necessary to have reagents that allow the
      discrimination of infected and vaccinated animals. A list of 42 potential M.
      bovis-specific antigens was prepared by comparative analysis of the genomes of M.
      bovis, M. avium subsp. avium, M. avium subsp. paratuberculosis, and Streptomyces
      coelicolor. Potential antigens were tested by applying them in a high-throughput
      peptide-based screening system to M. bovis-infected and BCG-vaccinated cattle and
      to cattle without prior exposure to M. bovis. A response hierarchy of antigens
      was established by comparing responses in infected animals. Three antigens
      (Mb2555, Mb2890, and Mb3895) were selected for further study, as they were
      strongly recognized in experimentally infected animals but with low or no
      frequency in BCG-vaccinated and naive cows. Interestingly, all three antigens
      were recognized in animals vaccinated against Johne's disease, suggesting the
      presences of epitopes cross-reacting with M. avium subsp. paratuberculosis
      antigens. Eight peptides from the three antigens studied in detail were
      identified as immunodominant and were characterized in terms of major
      histocompatibility complex class II restriction element usage and shown to be
      restricted through both DR and DQ molecules. Reasons for antigenic cross
      reactivity with M. avium subsp. paratuberculosis and refinement of the in silico
      strategy to predict such cross-reactivity from the primary protein sequence will
      be discussed. Evaluation of the peptides identified from the three dominant
      antigens by use of larger field studies is now a priority.

PMID- 16426006
TI  - Generation of antibodies against bovine recombinant prion protein in various
      strains of mice.
AB  - Transmissible spongiform encephalopathies (TSEs), also known as prion diseases,
      belong to a group of neurodegenerative disorders affecting humans and animals. To
      date, definite diagnosis of prion disease can only be made by analysis of tissue
      samples for the presence of protease-resistant misfolded prion protein (PrP(Sc)).
      Monoclonal antibodies (MAbs) to the prion protein provide valuable tools for TSE
      diagnosis, as well as for basic research on these diseases. In this
      communication, the development of antibodies against recombinant bovine prion
      protein (brecPrP) in four strains of mice (BALB/c, ND4, SJL, and NZB/NZW F(1)) is
      described. Immunization of autoimmunity-prone NZB/NZW F(1) and SJL mice with
      brecPrP was applied to overcome self-tolerance against the prion protein. ND4 and
      SJL mice did not develop an immune response to brecPrP. BALB/c mice produced
      antibody titers of 1:1,000 to 1:1,500 in an enzyme-linked immunosorbent assay
      (ELISA), while NZB/NZW F(1) mice responded with titers of 1:7,000 to 1:11,000. A
      panel of 71 anti-brecPrP MAbs recognizing continuous and discontinuous epitopes
      was established from BALB/c and NZB/NZW F(1) mice. Seven anti-brecPrP MAbs
      reacted with both the cellular form of PrP and protease K-resistant PrP(Sc) from
      sheep brain in Western blot assays. The epitope specificity of these MAbs was
      determined, and applicability to immunohistochemical detection of prions was
      studied. The MAbs generated will be useful tools in the development of TSE
      immunochemical diagnosis and for research. This is the first report of the
      development of anti-PrP MAbs by use of autoimmune NZB/NZW F(1) mice as an
      alternative approach for the generation of PrP-specific MAbs.

PMID- 16426008
TI  - Mycoplasma suis antigens recognized during humoral immune response in
      experimentally infected pigs.
AB  - Today, serodiagnostic tests for Mycoplasma suis infections in pigs have low
      accuracies. The development of novel serodiagnostic strategies requires a
      detailed analysis of the humoral immune response elicited by M. suis and, in
      particular, the identification of antigenic proteins of the agent. For this
      study, indirect enzyme-linked immunosorbent assay (ELISA) and immunoblot analyses
      were performed using pre- and sequential postinoculation sera from M. suis
      infected and mock-infected control pigs. M. suis purified from porcine blood
      served as the antigen. Eight M. suis-specific antigens (p33, p40, p45, p57, p61,
      p70, p73, and p83) were identified as targets of the immunoglobulin G (IgG)
      antibody response during experimental infection, with p40, p45, and p70 being the
      preferentially recognized M. suis antigens. Besides the M. suis-specific
      antigens, porcine immunoglobulins were identified in blood-derived M. suis
      preparations. By immunoglobulin depletion, the specificity of the M. suis antigen
      for use in indirect ELISA was significantly improved. M. suis-specific Western
      blot and ELISA reactions were observed in all infected pigs by 14 days
      postinfection at the latest and until week 14, the end of the experiments. During
      acute clinical attacks of eperythrozoonosis, a derailment of the antibody
      response, determined by decreases in both the M. suis net ELISA values and the
      numbers of M. suis-specific immunoblot bands, was accompanied by peaking levels
      of autoreactive IgG antibodies. In conclusion, the M. suis-specific antigens
      found to stimulate specific IgG antibodies are potentially useful for the
      development of novel serodiagnostic tests.

PMID- 16426007
TI  - Cholera toxin indirectly activates human monocyte-derived dendritic cells in
      vitro through the production of soluble factors, including prostaglandin E(2) and
      nitric oxide.
AB  - Cholera toxin (CT) is a potent adjuvant that activates dendritic cells (DC) by
      increasing intracellular cyclic AMP (cAMP) levels. In vivo and in vitro, very
      small amounts of CT induce potent adjuvant effects and activate DC. We
      hypothesized that DC intoxicated by CT may release factors that enhance their own
      maturation and induce the maturation of toxin-free bystander DC. Through the use
      of mixed cultures and transwell cultures, we found that human monocyte-derived DC
      (MDDC) pulsed with CT or other cAMP-elevating agonists induce the maturation of
      bystander DC. Many DC agonists including CT increase the production of
      prostaglandin E(2) (PGE(2)) and nitric oxide (NO). For this reason, we determined
      whether the actions of PGE(2) or NO are involved in the maturation of MDDC
      induced by CT or dibutyryl-cAMP (d-cAMP). We found that blocking the production
      of PGE(2) or blocking prostaglandin receptors inhibited MDDC maturation induced
      by CT and d-cAMP. Likewise, sequestering NO or blocking the downstream actions of
      NO resulted in the inhibition of MDDC maturation induced by CT and d-cAMP. These
      results indicate that endogenously produced factors including PGE(2) and NO
      contribute to the maturation of DC induced by CT and that these factors
      participate in bystander DC maturation. The results of this study may help
      explain why bacterial toxins that elevate cAMP are such potent adjuvants.

PMID- 16426010
TI  - Epithelial toll-like receptor 5 is constitutively localized in the mouse cecum
      and exhibits distinctive down-regulation during experimental colitis.
AB  - We recently demonstrated that the pattern recognition receptors (PRRs) toll-like
      receptor 2 (TLR2), TLR4, and CD14 are expressed in mouse colonic epithelium in a
      compartmentalized manner. Here we report the localization of TLR5, the receptor
      for bacterial flagellin, and its distinctive down-regulation during experimental
      colitis. Guts from normal BALB/c mice and those with dextran sodium sulfate (DSS)
      induced colitis were compared. Each gut was divided into seven segments (stomach,
      small intestine [three parts], and colon [three parts]), and epithelial cells and
      crypt units were collected by scraping and EDTA treatment, respectively. Northern
      blotting showed that TLR5 mRNA was preferentially expressed in the epithelium of
      the proximal colon in normal mice. Laser capture microdissection coupled to
      reverse transcriptase PCR confirmed this localization. TLR5 protein expression
      reflected mRNA expression, as evidenced by Western blotting. In mice with acute
      colitis, inflammation occurred mainly in the distal colon. Interestingly, while
      TLR2, TLR4, and CD14 were up-regulated in the inflamed colon, TLR5 was down
      regulated at both the mRNA and protein levels. Decreased TLR5 expression was more
      evident during chronic colitis. Additional in vitro studies using a mouse cell
      line, Colon-26, showed that gamma interferon (IFN-gamma) time- and dose
      dependently down-regulates TLR5. In conclusion, epithelial cells, mainly in the
      proximal colon, constitutively express TLR5. TLR5 expression is down-regulated in
      vivo during acute and chronic DSS-induced colitis, in contrast to the expression
      of TLR2, TLR4, and CD14. The mechanism governing TLR5 regulation may therefore
      differ from that controlling other PRRs. Finally, IFN-gamma may be involved in
      down-regulating TLR5 expression.

PMID- 16426011
TI  - Multilocus sequence types, serotypes, and variants of the surface antigen PspA in
      Streptococcus pneumoniae isolates from meningitis patients in Poland.
AB  - Meningitis caused by Streptococcus pneumoniae represents an important factor of
      morbidity and mortality in humans. In a significant number of cases, this disease
      is associated with specific clones of the organism, the so-called invasive
      pneumococcal clones. The aim of the study was to analyze 156 S. pneumoniae
      isolates identified as etiological agents of meningitis in Poland in the years
      1997 through 2002. The isolates were characterized by multilocus sequence typing
      (MLST), and the results were compared with those obtained by pulsed-field gel
      electrophoresis (PFGE) and with the MLST data on invasive pneumococci from other
      countries. Eighty-nine different sequence types were found in the group of
      isolates, 50 of which had been known before including 19 of the major invasive
      clones. However, a significant fraction of the isolates possessed novel
      combinations of known and new MLST alleles. The majority of penicillin
      nonsusceptible isolates belonged to the group of international multiresistant
      clones (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, Poland(23F)-16, and Poland(6B)
      20), which underlined the importance of these in the dissemination of
      antimicrobial resistance. The results of the MLST analysis correlated well with
      the PFGE data, thus again demonstrating good congruence between the two typing
      methods for S. pneumoniae. The majority of the isolates (95.5%) belonged to
      families 1 or 2 of the surface protein PspA, confirming its potential usefulness
      as the vaccine antigen candidate.

PMID- 16426009
TI  - Longitudinal analysis of cryptosporidium species-specific immunoglobulin G
      antibody responses in Peruvian children.
AB  - Cryptosporidium species are ubiquitous in the environment and are frequently
      detected in the stools of children who live where sanitation conditions are poor.
      To better characterize the immune response to these parasites, we monitored
      immunoglobulin G (IgG) antibody levels in a cohort of children from Lima, Peru.
      Two new enzyme-linked immunosorbent assays based on the C. parvum (bovine,
      subtype IIa) Iowa strain 17-kDa and 27-kDa antigens were used to measure IgG
      antibody levels in longitudinal serum samples. Antibody responses were detected
      during infections with C. parvum, C. felis, and C. meleagridis and with four
      different subtypes of C. hominis. We also noted that the magnitude of the
      antibody response was related to the number of previous infections and that older
      children generally had higher levels of antibodies to the two C. parvum antigens.
      Antibody responses were not associated with infections with either Cyclospora sp.
      or Giardia sp. We believe the antibody assays will be important tools for
      monitoring the success of future public health interventions.

PMID- 16426012
TI  - Reverse line blot assay for direct identification of seven Streptococcus
      agalactiae major surface protein antigen genes.
AB  - We developed a multiplex PCR-based reverse line blot hybridization assay
      (mPCR/RLB) to detect the genes encoding members of the family of variable surface
      localized proteins of Streptococcus agalactiae (group B streptococcus [GBS]),
      namely, Bca (Calpha), Rib, Epsilon (Epsilon/Alp1/Alp5), Alp2, Alp3, and Alp4, and
      the immunoglobulin A binding protein, Bac (Cbeta). We used the assay to identify
      these genes in a collection of well-characterized GBS isolates and reference
      strains. The results showed that mPCR/RLB avoids the common problems of cross
      reaction and nontypability associated with protein typing using antisera. It is
      as sensitive as, but more practical than, separate gene-specific PCRs and would
      be suitable for large molecular epidemiological studies of GBS.

PMID- 16426013
TI  - Evaluation of the INOVA diagnostics enzyme-linked immunosorbent assay kits for
      measuring serum immunoglobulin G (IgG) and IgA to deamidated gliadin peptides.
AB  - New assays for antibodies to deamidated gliadin peptides (DGP) expressing celiac
      disease-specific epitopes were evaluated using 154 sera previously tested for
      endomysial immunoglobulin A (IgA) (EMA), transglutaminase IgA (TGA), and
      conventional gliadin antibodies. DGP antibody results showed 97% concordance with
      EMA and TGA results. Of 56 sera negative for EMA and TGA but positive for
      conventional gliadin antibodies, 54 (96%) were negative for DGP antibodies.

PMID- 16426014
TI  - Ultrasensitive human immunodeficiency virus type 1 p24 antigen assay modified for
      use on dried whole-blood spots as a reliable, affordable test for infant
      diagnosis.
AB  - The ultrasensitive human immunodeficiency virus (HIV) p24 antigen assay was
      modified for use on pediatric dried whole-blood spots on Whatman no. 1 filter
      paper. The modified assay was found to be reliable and accurate, making it an
      affordable tool for pediatric HIV diagnosis in developing countries.

PMID- 16426015
TI  - Human endotoxemia induces down-regulation of monocyte CC chemokine receptor 2.
AB  - Upon injection of Escherichia coli lipopolysaccharide into human volunteers, the
      monocyte density of CC chemokine receptor 2 (CCR2) decreased. Minimal CCR2
      density was observed 4 h after injection. Peak plasma concentrations of the CCR2
      ligand monocyte chemotactic protein 1 and of tumor necrosis factor alpha were
      reached after 4 h and 2 h, respectively.

PMID- 16426016
TI  - Can the level of immunosuppression in human immunodeficiency virus-infected
      patients affect the reliability of human T-cell lymphotropic virus type 2
      serological diagnosis?
AB  - A total of 175 human immunodeficiency virus (HIV)-positive intravenous drug users
      (IDU) with CD4 cell counts of <200 cells/microl were matched with 175 HIV
      positive IDU with CD4 cell counts of >500 cells/microl. Enzyme immunoassay (EIA)
      reactivity and human T-cell lymphotropic virus type 2 (HTLV-2) Western blot (WB)
      positivity were more frequently observed in subjects with CD4 cell counts of >500
      cells/microl. Most of the subjects with low CD4 cell counts and EIA reactivity
      carried HTLV-2 infection (WB positive and/or PCR positive). No subjects with low
      CD4 cell counts and a lack of reactive EIA were PCR positive for HTLV-2.
      Therefore, a negative EIA result can confidently discharge HTLV-2 infection in
      HIV-infected patients with severe immunosuppression, whereas PCR should be
      performed for subjects with a reactive HTLV EIA which is not further confirmed by
      WB.

PMID- 16426018
TI  - The supply and demand for laboratory animal veterinarians from 1980 to 2005.

PMID- 16426017
TI  - Neutralizing and hemagglutination-inhibiting activities of antibodies elicited by
      the 2004-2005 influenza vaccine against drifted viruses.
AB  - Evaluation of the antibody responses induced by the 2004-2005 influenza vaccine
      strain against the homologous variant, the 2004-2005 field isolates, and a
      previous circulating strain showed that a correlation between neutralizing and
      hemagglutination-inhibiting activities exists only when the antigen is very close
      to the vaccine strain.

PMID- 16426019
TI  - Frequently asked questions about the Public Health Service Policy on Humane Care
      and Use of Laboratory Animals.

PMID- 16426020
TI  - An efficient approach to performing and documenting semiannual Institutional
      Animal Care and Use Committee inspections of animal facilities.

PMID- 16426022
TI  - Determination of microbiological contamination during long-term storage of
      sanitized equipment.

PMID- 16426021
TI  - The statistics and the issue of animal numbers in research.

PMID- 16426023
TI  - Continuous maintenance infusion technique for stable anesthesia in the dog, using
      alpha-chloralose.

PMID- 16426024
TI  - Technique for long-term catheterization of large abdominal vessels in growing
      cattle.

PMID- 16426025
TI  - Effects of caging type and group size on selected physiologic variables in rats.

PMID- 16426026
TI  - Evaluation of five treatment regimens and five diagnostic methods for murine
      mites (Myocoptes musculinus and Myobia musculi).

PMID- 16426027
TI  - Modification of the Bollman/Van Hook method of a two-stage hepatectomy in the
      rat: a simpler and safer surgical technique.

PMID- 16426028
TI  - A method for minimizing the effects of biologic diversity on the measurement of
      tumor growth rates.

PMID- 16426029
TI  - Ovarian teratoma in a pigtailed macaque (Macaca nemestrina).

PMID- 16426031
TI  - Retroperitoneal hematoma in a baboon.

PMID- 16426030
TI  - Special considerations for keeping cephalopods in laboratory facilities.

PMID- 16426032
TI  - Fourth Indo-U.S. Workshop on Mathematical Chemistry, January 8-12, 2005, Pune,
      Maharashtra, India.

PMID- 16426033
TI  - "Anticonnectivity": a challenge for structure-property-activity studies.
AB  - The higher-order variable connectivity indices were introduced to account for the
      combination of positive and negative relative contributions of atoms and bonds in
      the construction of the quantitative structure-property relationships or
      quantitative structure-activity relationships models. The coding capabilities of
      modified descriptors were presented on the modeling of the atmospheric reaction
      rate constants of selected organic compounds with OH radicals. The optimization
      of diagonal weights of the augmented adjacency matrix pointed out the significant
      enhancing effect of oxygen and the suppressive effect of chlorine on the overall
      molecular atmospheric reactivity of organic compounds with OH radicals. The
      linear regression model, using a single structural descriptor, that is, a
      variable connectivity index of order one, produced a root-mean-square error of
      0.343 log units. Although the obtained calculation error was higher than in
      previously reported multiple linear regression models, the new model offered
      important insight into the role of the individual structural components that are
      influencing the reactivity of organic compounds.

PMID- 16426034
TI  - Combining chemodescriptors and biodescriptors in quantitative structure-activity
      relationship modeling.
AB  - In view of the wide distribution of halocarbons in our world, their toxicity is a
      public health concern. Previous work has shown that various measures of toxicity
      can be predicted with standard molecular descriptors. In our work, biodescriptors
      of the effect of halocarbons on the liver were obtained by exposing hepatocytes
      to 14 halocarbons and a control and by producing two-dimensional electrophoresis
      gels to assess the expressed proteome. The resulting spot abundances provide
      additional biological information that might be used in toxicity prediction. QSAR
      models were fitted via ridge regression to predict eight dependent toxicity
      measures: d37, arr, EC50MTT, EC50LDH, EC20SH, LECLP, LECROS, and LECCAT. Three
      predictor sets were used for each-the chemodescriptors alone, the biodescriptors
      alone, and the combined set of both chemo- and biodescriptors. The results
      differed somewhat from one dependent to another, but overall it was shown that
      better results could be obtained by using both chemo- and biodescriptors in the
      model than by using either chemo- or biodescriptors alone. The library of
      compounds used was small and quite homogeneous, so our immediate conclusions are
      correspondingly limited in scope, but we believe the underlying methodologies
      have broad applicability at the interface of chemical and biological descriptors.

PMID- 16426035
TI  - Developing an antituberculosis compounds database and data mining in the search
      of a motif responsible for the activity of a diverse class of antituberculosis
      agents.
AB  - A novel data mining procedure to look for new antitubercular agents and targets
      as well as to find a minimum common bioactive substructure (MCBS), has been
      reported here. The methodology extracts MCBS, both across the diverse chemical
      classes and within the particular chemical class, known to be present in the
      various marketed drugs alongside antimycobacterial compounds with known MICs. For
      this purpose a small in-house database of compounds has been created, for which
      MICs against Mycobacterium are known. The compounds have been collected from
      literature available on the synthetic compounds, having known MICs against
      Mycobacterium tuberculosis. An elaborate HQSAR (Hologram QSAR) study has been
      attempted to extract active fragment from a diverse class of compounds, in
      combination with the clustering technique to select a homogeneous group of
      compounds having good a profile toward the activity. The 2D pharmacophore (the 2D
      fragments extracted from HQSAR) has been validated searching the database. It has
      been found further that this validated 2D pharmacophore could be used for
      searching the orphan target in Mycobacterium effectively.

PMID- 16426036
TI  - Three-dimensional QSAR using the k-nearest neighbor method and its
      interpretation.
AB  - In this paper we report a novel three-dimensional QSAR approach, kNN-MFA,
      developed based on principles of the k-nearest neighbor method combined with
      various variable selection procedures. The kNN-MFA approach was used to generate
      models for three different data sets and predict the activity of test molecules
      through each of these models. The three data sets used were the standard steroid
      benchmark, an antiinflammatory and an anticancerous data set. The study resulted
      in kNN-MFA models having better statistical parameters than the reported CoMFA
      models for all the three data sets. It was also found that stochastic methods
      generate better models resulting in more accurate predictions as compared to
      stepwise forward selection procedures. Thus, kNN-MFA method represents a good
      alternative to CoMFA-like methods.

PMID- 16426037
TI  - Comparing the information content of two large olfactory databases.
AB  - The expert's subjectivity in establishing an olfactory description can produce
      wide discrepancies in different databases listing the odor profile of identical
      compounds. A representative example is obtained by comparing the odorous
      compounds included in the "Perfumery Materials and Performance 2001" (PMP2001)
      database and in Arctander's books (1960 and 1969). To better assess this problem,
      classification models obtained by using the adaptive fuzzy partition method were
      established on subsets of these databases distributed into the same olfactory
      classes. The robustness and the prediction power of these models give a powerful
      criterion for evaluating the "quality" of their information content and for
      deciding which is the most trustable database.

PMID- 16426039
TI  - A simple algorithm for unique representation of chemical structures
      cyclic/acyclic functionalized achiral molecules.
AB  - An algorithm, based on "vertex priority values" has been proposed to uniquely
      sequence and represent connectivity matrices of chemical structures of
      cyclic/acyclic functionalized achiral hydrocarbons and their derivatives. In this
      method, "vertex priority values" have been assigned in terms of atomic weights,
      subgraph lengths, loops, and heteroatom contents. Subsequently, the terminal
      vertices have been considered upon completing the sequencing of the core
      vertices. This approach provides a multilayered connectivity graph, which can be
      put to use in comparing two or more structures or parts thereof for any given
      purpose. Furthermore, the basic vertex connection tables generated here are
      useful in the computation of characteristic matrices/topological indices and
      automorphism groups and in storing, sorting, and retrieving chemical structures
      from databases.

PMID- 16426038
TI  - Evaluation of binary QSAR models derived from LUDI and MOE scoring functions for
      structure based virtual screening.
AB  - In today's world of high-throughput in silico screening, the development of
      virtual screening methodologies to prioritize small molecules as new chemical
      entities (NCEs) for synthesis is of current interest. Among several approaches to
      virtual screening, structure-based virtual screening has been considered the most
      effective. However the problems associated with the ranking of potential
      solutions in terms of scoring functions remains one of the major bottlenecks in
      structure-based virtual screening technology. It has been suggested that scoring
      functions may be used as filters for distinguishing binders from nonbinders
      instead of accurately predicting their binding free energies. Subsequently,
      several improvements have been made in this area, which include the use of
      multiple rather than single scoring functions and application of either consensus
      or multivariate statistical methods or both to improve the discrimination between
      binders and nonbinders. In view of it, the discriminative ability (distinguishing
      binders from nonbinders) of binary QSAR models derived using LUDI and MOE scoring
      functions has been compared with the models derived by Jacobbsson et al. on five
      data sets viz. estrogen receptor alphamimics (ERalpha_mimics), estrogen receptor
      alphatoxins (ERalpha_toxins), matrix metalloprotease 3 inhibitors (MMP-3), factor
      Xa inhibitors (fXa), and acetylcholine esterase inhibitors (AChE). The overall
      analyses reveal that binary QSAR is comparable to the PLS discriminant analysis,
      rule-based, and Bayesian classification methods used by Jacobsson et al. Further
      the scoring functions implemented in LUDI and MOE can score a wide range of
      protein-ligand interactions and are comparable to the scoring functions
      implemented in ICM and Cscore. Thus the binary QSAR models derived using LUDI and
      MOE scoring functions may be useful as a preliminary screening layer in a
      multilayered virtual screening paradigm.

PMID- 16426040
TI  - Partitioning of pi-electrons in rings for Clar structures of benzenoid
      hydrocarbons.
AB  - Resonance structures of polycyclic aromatic hydrocarbons can be associated with
      numerical formulas by assigning pi-electrons of C=C double bonds to individual
      benzenoid rings. Each C=C double bond in a resonance structure assigns two pi
      electrons to a ring in a fused-benzenoid system if it is not shared by adjacent
      rings and one pi-electron when it is common to two rings, obtaining thus a
      "local" characterization of rings in polycyclic conjugated hydrocarbons. In the
      present contribution we extend this approach to the aromatic pi-sextet model of
      Clar, which offers an alternative description of benzenoid hydrocarbons. In this
      model local characteristics of individual benzenoid rings are based on
      partitioning of pi-electrons but only for those resonance structures (fewer in
      number) that contribute to Clar's formula of benzenoid hydrocarbons.

PMID- 16426041
TI  - Quantitative structure-activity relationship modeling of juvenile hormone mimetic
      compounds for Culex pipiens larvae, with a discussion of descriptor-thinning
      methods.
AB  - Quantitative structure-activity relationship (QSAR) modelers often encounter the
      problem of multicollinearity owing to the availability of large numbers of
      computable molecular descriptors. Sparsity of the variables while using
      descriptors such as atom pairs increases the complexity. Three different
      predictor-thinning methods, namely, a modified Gram-Schmidt algorithm, a marginal
      soft thresholding algorithm, and LASSO (least absolute shrinkage and selection
      operator), were utilized to reduce the number of descriptors prior to developing
      linear models. Juvenile hormone (JH) activity of 304 compounds on Culex pipiens
      larvae was taken as the model data set, and predictor trimming of a large number
      of diverse descriptors comprising 268 global molecular descriptors
      (topostructural, topochemical, and geometrical), 13 quantum chemical descriptors,
      and 915 atom pairs (substructural counts) was applied prior to linear regression
      by the ridge regression method. The data set (N = 304) was split into five
      calibration data sets of random samples of sizes 60/110/160/210/260, and the
      remaining 244/194/144/94/44 compounds were used for validations. LASSO was not
      found to be a very effective method in handling a large set of descriptors
      because the number of predictors retained could not exceed the number of
      observations. The results indicated that the modified Gram-Schmidt algorithm
      could be used to trim the number of predictors in the global molecular descriptor
      set where collinearity of the descriptors was the major concern. On the contrary,
      the soft thresholding approach was found to be an effective tool in subset
      selection from a diverse set of descriptors having both sparsity and
      multicollinearity, as in the case of the combined set of atom pairs and global
      molecular descriptors. The final model developed after variable selection was
      dominated more by atom pairs, which indicated the important structural moieties
      that affect JH activity of the compounds. The success of the method reiterates
      the fact that QSAR or quantitative structure-property relationship (QSPR) models
      can be developed for a diverse set of compounds using properly parametrized and
      diverse sets of descriptors, of course, with the selection of the appropriate
      statistical tools.

PMID- 16426042
TI  - A physicochemical model for analyzing DNA sequences.
AB  - In search of an ab initio model to characterize DNA sequences as genes and
      nongenes, we examined some physicochemical properties of each trinucleotide
      (codon), which could accomplish this task. We constructed three-dimensional
      vectors for each double-helical trinucleotide sequence considering hydrogen
      bonding energy, stacking energy, and a third parameter, which we provisionally
      identified with DNA-protein interactions. As this three-dimensional vector moves
      along any genome, the net orientation of the resultant vector should differ
      significantly for gene and nongene regions to make a distinction feasible, if the
      underlying model has some merits. An analysis of 331 prokaryotic genomes
      comprising a total of 294 786 experimentally verified genes (nonoverlapping) and
      an equal number of nongenes presents a proof of concept of the model without the
      need for further parametrization. Also, initial analyses on Saccharomyces
      cerevisiae and Arabidopsis thaliana suggest that the methodology is extendable to
      eukaryotes. The physicochemical model (ChemGenome1.0) introduced has the
      potential to be developed into a gene-finding algorithm and, more pressingly,
      could be employed for an independent assessment of the annotation of DNA
      sequences.

PMID- 16426043
TI  - A high dimensional QSAR study on the aldose reductase inhibitory activity of some
      flavones: topological descriptors in modeling the activity.
AB  - The quantitative structure-activity relationships (QSAR) of the Aldose Reductase
      (AR) inhibitory activity of 48 flavones were studied using Free-Wilson,
      Combinatorial Protocol in Multiple Linear Regression (CP-MLR), and Partial Least
      Squares (PLS) procedures. For the latter two procedures 152 Molconn-Z parameters
      and six indicators corresponding to the hydroxyls of flavones were used as
      molecular descriptors. Independently, all procedures suggested the significance
      of hydroxyls in modulating the activity of these compounds. The CP-MLR procedure
      identified 26 descriptors to model the activity. They suggested that structures
      rich in aromatic CH fragments, with a limited number of aliphatic fragments such
      as -CH2-, -CH<, and free hydroxyls at 7-, 3'-, and 4'-positions of the 2
      arylbenzpyran-4-one core would be preferred for the activity. The PLS analysis
      agreed with the information content and the relative significance of the
      descriptors identified in the CP-MLR for modeling the activity. The study offers
      the scope to modulate the inhibitory activity of these compounds.

PMID- 16426044
TI  - Topological descriptors in modeling the antimalarial activity of 4-(3',5'
      disubstituted anilino)quinolines.
AB  - Two series of closely related antimalarial agents, 7-chloro-4-(3',5'
      disubstituted anilino)quinolines, have been analyzed using Combinatorial Protocol
      in Multiple Linear Regression (CP-MLR) for the structure-activity relations with
      more than 450 topological descriptors for each set. The study clearly suggested
      that 3'- and 5'-substituents of the anilino moiety map different domains in the
      activity space. While one domain favors the compact structural frames having
      aromatic, heterocyclic ring(s) substituted with closely spaced F, NO(2), and O
      functional groups, the other prefers structural frames enriched with
      unsaturation, loops, branches, electronic content, and devoid of carbonyl
      function. Also, this study gives an indication in favor of the electron rich
      centers in the aniline substituent groups for better antimalarial activity, an
      observation in line with several of the previous reports too. The models
      developed, and the participating descriptors suggest that the substituent groups
      of the 4-anilino moiety of the 4-(3',5'-disubstituted anilino)quinolines hold
      scope for further modification in the optimization of the antimalarial activity.

PMID- 16426045
TI  - QSAR and SAR studies on the reduction of some aromatic nitro compounds by
      xanthine oxidase.
AB  - This work describes QSAR and SAR studies on the reduction of 27 aromatic nitro
      compounds by xanthine oxidase using both distance-based topological indices and
      quantum molecular descriptors along with indicator parameters. The application of
      a multiple linear regression analysis indicated that a combination of distance
      based topological indices with the ad hoc molecular descriptors and the indicator
      parameters yielded a statistically significant model for the activity, log K (the
      reduction of aromatic nitro compounds by xanthine oxidase). The final selection
      of a potential aromatic nitro compound for the reduction by xanthine oxidase is
      made by quantum molecular modeling. We have found that, among the various
      parameters, the quantum Mulliken charge parameters on the fourth atom or para
      position relative to the nitro group correlated best with the activity.

PMID- 16426046
TI  - Proteomics and bioinformatics strategies to design countermeasures against
      infectious threat agents.
AB  - The potential devastation resulting from an intentional outbreak caused by
      biological warfare agents such as Brucella abortus and Bacillus anthracis
      underscores the need for next generation vaccines. Proteomics, genomics, and
      systems biology approaches coupled with the bacterial ghost (BG) vaccine delivery
      strategy offer an ideal approach for developing safer, cost-effective, and
      efficacious vaccines for human use in a relatively rapid time frame. Critical to
      any subunit vaccine development strategy is the identification of a pathogen's
      proteins with the greatest potential of eliciting a protective immune response.
      These proteins are collectively referred to as the pathogen's immunome.
      Proteomics provides high-resolution identification of these immunogenic proteins
      using standard proteomic technologies, Western blots probed with antisera from
      infected patients, and the pathogen's sequenced and annotated genome. Selected
      immunoreactive proteins can be then cloned and expressed in nonpathogenic Gram
      negative bacteria. Subsequently, a temperature shift or chemical induction
      process is initiated to induce expression of the PhiX174 E-lysis gene, whose
      protein product forms an E tunnel between the inner and outer membrane of the
      bacteria, expelling all intracellular contents. The BG vaccine system is a proven
      strategy developed for many different pathogens and tested in a complete array of
      animal models. The BG vaccine system also has great potential for producing
      multiagent vaccines for protection to multiple species in a single formulation.

PMID- 16426047
TI  - On the dependence of a characterization of proteomics maps on the number of
      protein spots considered.
AB  - We have reexamined the numerical characterization of proteomics maps based on the
      construction of novel distance matrices associated with the nearest neighbor
      graph for the protein spots. In particular we consider dependence of a
      characterization of proteomics map on the number of proteins considered in the
      analysis. We examined a collection of proteomics maps in which we approximately
      doubled the number of spots to be used for quantitative analysis, considering
      cases of maps having 30, 50, 100, 250, 500, and 1054 protein spots. For each case
      we have compared the similarity-dissimilarity results for five proteomics maps of
      rat liver cells associated with the control group and four proliferators
      administrated by intraperitoneal injection. We found that proteins maps based on
      a set of about the 250 most abundant proteins spots suffice for a satisfactory
      numerical characterization of such maps.

PMID- 16426048
TI  - Correlation of the side-chain hubs with the functional residues in DNA binding
      protein structures.
AB  - The structure networks of DNA-binding proteins have been constructed and
      analyzed. The detailed analysis of the networks indicates a strong relation
      between the positions of the residues interacting with DNA and those that form
      extensive interactions within the protein structure (called hubs). This study
      shows that the functional residues in these proteins are held in place by
      efficient scaffolding of the structure using side-chain interactions, thus
      highlighting the role of these side-chain hubs with respect to the functional
      residues in the protein structure.

PMID- 16426049
TI  - Proteomic maps-toxicity relationship of halocarbons studied with similarity index
      and genetic algorithm.
AB  - In this work we analyzed proteomic maps obtained from hepatocytes, which were
      treated with 14 halocarbons. A similarity index was introduced as a robust
      measure of similarity between two maps or between two selections of spots within
      the maps. A searching algorithm was used to identify the spots that may play an
      important role in toxicity mechanism. The highest correlation coefficients
      obtained between the similarity index and biological parameter were larger than
      0.9.

PMID- 16426050
TI  - Supervised self-organizing maps in drug discovery. 2. Improvements in descriptor
      selection and model validation.
AB  - The modeling of nonlinear descriptor-target relationships is a topic of
      considerable interest in drug discovery. We, herein, continue reporting the use
      of the self-organizing map-a nonlinear, topology-preserving pattern recognition
      technique that exhibits considerable promise in modeling and decoding these
      relationships. Since simulated annealing is an efficient tool for solving
      optimization problems, we combined the supervised self-organizing map with
      simulated annealing to build high-quality, highly predictive quantitative
      structure-activity/property relationship models. This technique was applied to
      six data sets representing a variety of biological endpoints. Since a high
      statistical correlation in the training set does not indicate a highly predictive
      model, the quality of all the models was confirmed by withholding a portion of
      each data set for external validation. Finally, we introduce new cross-validation
      and dynamic partitioning techniques to address model overfitting and assessment.

PMID- 16426051
TI  - Chemical markup, XML, and the world wide web. 6. CMLReact, an XML vocabulary for
      chemical reactions.
AB  - A set of components (CMLReact) for managing chemical and biochemical reactions
      has been added to CML. These can be combined to support most of the strategies
      for the formal representation of reactions. The elements, attributes, and types
      are formally defined as XMLSchema components, and their semantics are developed.
      New syntax and semantics in CML are reported and illustrated with 10 examples.

PMID- 16426052
TI  - Screening for new antidepressant leads of multiple activities by support vector
      machines.
AB  - Virtual screening was carried out against 21 biological targets related to
      depression by support vector machine classification using the same atom-type
      descriptors. The models were effective as 0.2-0.8 of theoretical enrichments of
      the external test data sets could be achieved, depending on the target. The set
      of predicted active molecules had large diversity and contained examples with
      high dissimilarity to the compounds of training sets. Filtering the database of
      known antidepressants by all 21 models it was found that on average compounds
      were classified active for 2.3 targets.

PMID- 16426053
TI  - A multivariate analysis of HIV-1 protease inhibitors and resistance induced by
      mutation.
AB  - This paper describes the use of the multivariate statistical procedure principal
      component analysis as a tool to explore the inhibitory activity of classes of
      protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent
      single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis
      of correlations between biological activity and molecular descriptors or
      similarity indexes allowed a reliable classification of the 51 derivatives
      considered in this study. The best results were obtained in the case of the I84V
      mutant for which a high number of predictions was achieved. On this basis, this
      statistical approach is proposed as a reliable method for the prediction of the
      activity of PIs, for which the data against mutant strains have not been
      reported.

PMID- 16426054
TI  - Molecular transformations as a way of finding and exploiting consistent local
      QSAR.
AB  - The idea of a "transformation", making a small change to a chemical structure,
      for instance removing or replacing a substituent, is familiar to chemists. We
      suggest two ways of representing a transformation in silico, as a substructure
      descriptor difference vector, and as the set of atoms remaining once a maximum
      common substructure is eliminated. Such transformations can be filtered sensibly,
      and it is easy to compare one transformation to another. These representations
      have two applications. First, we can use these methods to automatically organize
      and display sets of closely related compounds such that any consistent local QSAR
      in a data set can be easily seen, the T-ANALYZE application. Second, we can
      suggest to a chemist how to change a molecule "on hand" to a more active one
      based on local QSAR for that activity, the T-MORPH application.

PMID- 16426055
TI  - Enrichment of high-throughput screening data with increasing levels of noise
      using support vector machines, recursive partitioning, and laplacian-modified
      naive bayesian classifiers.
AB  - High-throughput screening (HTS) plays a pivotal role in lead discovery for the
      pharmaceutical industry. In tandem, cheminformatics approaches are employed to
      increase the probability of the identification of novel biologically active
      compounds by mining the HTS data. HTS data is notoriously noisy, and therefore,
      the selection of the optimal data mining method is important for the success of
      such an analysis. Here, we describe a retrospective analysis of four HTS data
      sets using three mining approaches: Laplacian-modified naive Bayes, recursive
      partitioning, and support vector machine (SVM) classifiers with increasing
      stochastic noise in the form of false positives and false negatives. All three of
      the data mining methods at hand tolerated increasing levels of false positives
      even when the ratio of misclassified compounds to true active compounds was 5:1
      in the training set. False negatives in the ratio of 1:1 were tolerated as well.
      SVM outperformed the other two methods in capturing active compounds and
      scaffolds in the top 1%. A Murcko scaffold analysis could explain the differences
      in enrichments among the four data sets. This study demonstrates that data mining
      methods can add a true value to the screen even when the data is contaminated
      with a high level of stochastic noise.

PMID- 16426056
TI  - Visualization and interpretation of high content screening data.
AB  - High content screening is a method for identifying small molecule modulators of
      mammalian cell biology. The nature of the experiment generates an enormous amount
      of data in the form of photographic images of cells after treatment with
      compounds of interest. The interpretation of data from these experiments is
      challenging both in terms of automatically perceiving the images, extracting, and
      understanding differences between screened compounds and visualizing the results.
      This paper discusses the application of statistical and visual methods that have
      been used to interpret data from a simplified DNA stain (DAPI) screen to quickly
      identify compounds of interest. An understanding of the mechanism of action of
      the screened compounds can be obtained by comparing them to control compounds of
      known mechanism of action. Statistical and visual methods will be shown that
      facilitate easy comparison of screened compounds against these control compounds.
      As an example, a subset of the internal repository at ArQule was screened,
      together with control compounds that were known to induce characteristic mitotic
      arrest. Subsequent data processing described in this paper permitted the easy
      identification of compounds that were similar to (and very different from) the
      control compounds.

PMID- 16426057
TI  - ErG: 2D pharmacophore descriptions for scaffold hopping.
AB  - An extended reduced graph approach (ErG) is presented that uses pharmacophore
      type node descriptions to encode the relevant molecular properties. The basic
      idea of the method can be described as a hybrid approach of reduced graphs
      (Gillet et al. J. Chem. Inf. Comput. Sci. 2003, 43, 338-345) and binding property
      pairs (Kearsley et al. J. Chem. Inf. Comput. Sci. 1996, 36, 118-127). However,
      specific extension modifications to correctly describe the pharmacophoric
      properties, size, and shape of the molecules under study result in a very stable
      and good performance as compared to DAYLIGHT fingerprints (DFP). This is
      exemplified for 11 activity classes of the MDL Drug Data Report database, for
      which ErG performs as well or better than DFP in 10 cases. On the basis of the
      example data sets, the ability of ErG to switch from one chemotype to another
      (often referred to as "scaffold hopping") is highlighted. Additionally, possible
      pitfalls of reduced graph approaches as well as suitable solutions are discussed
      with the help of example structures. Overall, it is shown that ErG is a widely
      applicable method capable of identifying structurally diverse actives for a given
      active search query. This diversity is achieved by a high degree of molecular
      abstraction, which in turn results in a low dimensional descriptor vector that
      allows very low computation times for similarity searches.

PMID- 16426058
TI  - VISCANA: visualized cluster analysis of protein-ligand interaction based on the
      ab initio fragment molecular orbital method for virtual ligand screening.
AB  - We have developed a visualized cluster analysis of protein-ligand interaction
      (VISCANA) that analyzes the pattern of the interaction of the receptor and ligand
      on the basis of quantum theory for virtual ligand screening. Kitaura et al.
      (Chem. Phys. Lett. 1999, 312, 319-324.) have proposed an ab initio fragment
      molecular orbital (FMO) method by which large molecules such as proteins can be
      easily treated with chemical accuracy. In the FMO method, a total energy of the
      molecule is evaluated by summation of fragment energies and interfragment
      interaction energies (IFIEs). In this paper, we have proposed a cluster analysis
      using the dissimilarity that is defined as the squared Euclidean distance between
      IFIEs of two ligands. Although the result of an ordered table by clustering is
      still a massive collection of numbers, we combine a clustering method with a
      graphical representation of the IFIEs by representing each data point with colors
      that quantitatively and qualitatively reflect the IFIEs. We applied VISCANA to a
      docking study of pharmacophores of the human estrogen receptor alpha ligand
      binding domain (57 amino acid residues). By using VISCANA, we could classify even
      structurally different ligands into functionally similar clusters according to
      the interaction pattern of a ligand and amino acid residues of the receptor
      protein. In addition, VISCANA could estimate the correct docking conformation by
      analyzing patterns of the receptor-ligand interactions of some conformations
      through the docking calculation.

PMID- 16426059
TI  - Grand canonical Monte Carlo simulation of ligand-protein binding.
AB  - A new application of the grand canonical thermodynamics ensemble to compute
      ligand-protein binding is described. The described method is sufficiently rapid
      that it is practical to compute ligand-protein binding free energies for a large
      number of poses over the entire protein surface, thus identifying multiple
      putative ligand binding sites. In addition, the method computes binding free
      energies for a large number of poses. The method is demonstrated by the
      simulation of two protein-ligand systems, thermolysin and T4 lysozyme, for which
      there is extensive thermodynamic and crystallographic data for the binding of
      small, rigid ligands. These low-molecular-weight ligands correspond to the
      molecular fragments used in computational fragment-based drug design. The
      simulations correctly identified the experimental binding poses and rank ordered
      the affinities of ligands in each of these systems.

PMID- 16426060
TI  - Physics-based scoring of protein-ligand complexes: enrichment of known inhibitors
      in large-scale virtual screening.
AB  - We demonstrate that using an all-atom molecular mechanics force field combined
      with an implicit solvent model for scoring protein-ligand complexes is a
      promising approach for improving inhibitor enrichment in the virtual screening of
      large compound databases. The rescoring method is evaluated by the extent to
      which known binders for nine diverse, therapeutically relevant enzymes are
      enriched against a background of approximately 100,000 drug-like decoys. The
      improvement in enrichment is most robust and dramatic within the top 1% of the
      ranked database, that is, the first thousand compounds; below the first few
      percent of the ranked database, there is little overall improvement. The improved
      early enrichment is likely due to the more realistic treatment of ligand and
      receptor desolvation in the rescoring procedure. We also present anecdotal but
      encouraging results assessing the ability of the rescoring method to predict
      specificity of inhibitors for structurally related proteins.

PMID- 16426061
TI  - New scoring functions for virtual screening from molecular dynamics simulations
      with a quantum-refined force-field (QRFF-MD). Application to cyclin-dependent
      kinase 2.
AB  - A recently introduced new methodology based on ultrashort (50-100 ps) molecular
      dynamics simulations with a quantum-refined force-field (QRFF-MD) is here
      evaluated in its ability both to predict protein-ligand binding affinities and to
      discriminate active compounds from inactive ones. Physically based scoring
      functions are derived from this approach, and their performance is compared to
      that of several standard knowledge-based scoring functions. About 40 inhibitors
      of cyclin-dependent kinase 2 (CDK2) representing a broad chemical diversity were
      considered. The QRFF-MD method achieves a correlation coefficient, R(2), of 0.55,
      which is significantly better than that obtained by a number of traditional
      approaches in virtual screening but only slightly better than that obtained by
      consensus scoring (R(2) = 0.50). Compounds from the Available Chemical Directory,
      along with the known active compounds, were docked into the ATP binding site of
      CDK2 using the program Glide, and the 650 ligands from the top scored poses were
      considered for a QRFF-MD analysis. Combined with structural information extracted
      from the simulations, the QRFF-MD methodology results in similar enrichment of
      known actives compared to consensus scoring. Moreover, a new scoring function is
      introduced that combines a QRFF-MD based scoring function with consensus scoring,
      which results in substantial improvement on the enrichment profile.

PMID- 16426062
TI  - QSAR and QSPR studies of a highly structured physicochemical domain.
AB  - The relevance of terms other than linear when deriving quantitative structure
      activity relationship/quantitative structure-property relationship (QSAR/QSPR)
      models has been rarely considered so far. In this study, the impact of quadratic
      and interacting terms has been taken into account. The first effect of including
      such highly structured terms is a significant extension of the parametric domain
      that moves from the initial N to N(N + 3)/2 parameters. This substantial
      enlargement over the conventional linear boundaries involves a higher
      computational cost due to the increased combinatorial number of resulting
      theoretical QSAR/QSPR models. To face this issue, novel genetic-algorithm-based
      software, MGZ (multigenetic zooming), was developed and used for both variable
      selection and model building. To speed up the entire process of domain searching,
      MGZ was supported with multiple independent evolving populations and genetic
      storms to further QSAR/QSPR analyses. In addition, a novel fitness function was
      developed to score models on the basis of their inner predictive capability,
      assessed on the training set, structure complexity, and presence of nonlinear
      terms. The models were further validated by monitoring model redundancy and
      performing intensive randomization runs. The Selwood data set was used as a
      reference set to derive QSAR models. Furthermore, a QSPR study was conducted on
      the solubility data set of a large array of organic compounds. The results
      reported in the present paper demonstrate that our approach is successful in
      finding linear models, which are at least as good as the models previously
      derived using standard statistical approaches, and in deriving new nonlinear
      models with good statistical figures.

PMID- 16426063
TI  - The use of consensus scoring in ligand-based virtual screening.
AB  - A new consensus approach has been developed for ligand-based virtual screening.
      It involves combining highly disparate properties in order to improve performance
      in virtual screening. The properties include structural, 2D pharmacophore and
      property-based fingerprints, scores derived using BCUT descriptors, and 3D
      pharmacophore approaches. Different approaches for the combination of all or some
      of these methods have been tested. Logistic regression and sum ranks were found
      to be the most advantageous in different pharmaceutical applications. The three
      major reasons consensus scoring appears to enrich data sets better than single
      scoring functions are (1) using multiple scoring functions is similar to repeated
      samplings, in which case the mean is closer to the true value than any single
      value, (2) due to the better clustering of actives, multiple sampling will
      recover more actives than inactives, and (3) different methods seem to agree more
      on the ranking of the actives than on the inactives. Furthermore, consensus
      results are not only better but are also more consistent across receptor systems.

PMID- 16426064
TI  - In silico prediction of blood brain barrier permeability: an Artificial Neural
      Network model.
AB  - This paper has two objectives: first to develop an in silico model for the
      prediction of blood brain barrier permeability of new chemical entities and
      second to find the role of active transport specific to the P-glycoprotein (P-gp)
      substrate probability in blood brain barrier permeability. An Artificial Neural
      Network (ANN) model has been developed to predict the ratios of the steady-state
      concentrations of drugs in the brain to those in the blood (logBB) from their
      molecular structural parameters. Seven descriptors including P-gp substrate
      probability have been used for model development. The developed model is able to
      capture a relationship between P-gp and logBB. The predictive ability of the ANN
      model has also been compared with earlier computational models.

PMID- 16426065
TI  - FLAME: a program to flexibly align molecules.
AB  - Herein, we describe a method to flexibly align molecules (FLAME = FLexibly Align
      MolEcules). FLAME aligns two molecules by first finding maximum common
      pharmacophores between them using a genetic algorithm. The resulting alignments
      are then subjected to simultaneous optimizations of their internal energies and
      an alignment score. The utility of the method in pairwise alignment, multiple
      molecule flexible alignment, and database searching was examined. For pairwise
      alignment, two carboxypeptidase ligands (Protein Data Bank codes and ), two
      estrogen receptor ligands ( and ), and two thrombin ligands ( and ) were used as
      test sets. Alignments generated by FLAME starting from CONCORD structures
      compared very well to the X-ray structures (average root-mean-square deviation =
      0.36 A) even without further minimization in the presence of the protein. For
      multiple flexible alignments, five structurally diverse D3 receptor ligands were
      used as a test set. The FLAME alignment automatically identified three common
      pharmacophores: a base, a hydrogen-bond acceptor, and a hydrophobe/aromatic ring.
      The best alignment was then used to search the MDDR database. The search results
      were compared to the results using atom pair and Daylight fingerprint similarity.
      A similar database search comparison was also performed using estrogen receptor
      modulators. In both cases, hits identified by FLAME were structurally more
      diverse compared to those from the atom pair and Daylight fingerprint methods.

PMID- 16426066
TI  - The eight classes of positive-curvature graphitic nanocones.
AB  - The eight different classes of single-wall positive-curvature graphitic nanocones
      are emphasized, characterized, and illustrated. Local transformations among
      different possible apex-region structures within a common class are investigated,
      it being noted that there is no short sequence of such transformations which
      convert from any one of these eight classes to another. Attention is directed to
      class identification and to nanocone codes, especially for "buckycones" comprised
      solely from pentagonal and hexagonal rings.

PMID- 16426067
TI  - Scalable partitioning and exploration of chemical spaces using geometric hashing.
AB  - Virtual screening (VS) has become a preferred tool to augment high-throughput
      screening(1) and determine new leads in the drug discovery process. The core of a
      VS informatics pipeline includes several data mining algorithms that work on huge
      databases of chemical compounds containing millions of molecular structures and
      their associated data. Thus, scaling traditional applications such as
      classification, partitioning, and outlier detection for huge chemical data sets
      without a significant loss in accuracy is very important. In this paper, we
      introduce a data mining framework built on top of a recently developed fast
      approximate nearest-neighbor-finding algorithm(2) called locality-sensitive
      hashing (LSH) that can be used to mine huge chemical spaces in a scalable fashion
      using very modest computational resources. The core LSH algorithm hashes chemical
      descriptors so that points close to each other in the descriptor space are also
      close to each other in the hashed space. Using this data structure, one can
      perform approximate nearest-neighbor searches very quickly, in sublinear time. We
      validate the accuracy and performance of our framework on three real data sets of
      sizes ranging from 4337 to 249 071 molecules. Results indicate that the
      identification of nearest neighbors using the LSH algorithm is at least 2 orders
      of magnitude faster than the traditional k-nearest-neighbor method and is over
      94% accurate for most query parameters. Furthermore, when viewed as a data
      partitioning procedure, the LSH algorithm lends itself to easy parallelization of
      nearest-neighbor classification or regression. We also apply our framework to
      detect outlying (diverse) compounds in a given chemical space; this algorithm is
      extremely rapid in determining whether a compound is located in a sparse region
      of chemical space or not, and it is quite accurate when compared to results
      obtained using principal-component-analysis-based heuristics.

PMID- 16426069
TI  - Structure-based QSAR analysis of a set of 4-hydroxy-5,6-dihydropyrones as
      inhibitors of HIV-1 protease: an application of the receptor-dependent (RD) 4D
      QSAR formalism.
AB  - Receptor-dependent (RD) 4D-QSAR models were constructed for a set of 39 4-hydroxy
      5,6-dihydropyrone analogue HIV-1 protease inhibitors. The receptor model used in
      this QSAR analysis was derived from the HIV-1 protease (PDB ID ) crystal
      structure. The bound ligand in the active site of the enzyme, also a 4-hydroxy
      5,6-dihydropyrone analogue, was used as the reference ligand for docking the data
      set compounds. The optimized RD 4D-QSAR models are not only statistically
      significant (r(2) = 0.86, q(2) = 0.80 for four- and greater-term models) but also
      possess reasonable predictivity based on test set predictions. The proposed
      "active" conformations of the docked analogues in the active site of the enzyme
      are consistent in overall molecular shape with those suggested from
      crystallographic studies. Moreover, the RD 4D-QSAR models also "capture" the
      existence of specific induced-fit interactions between the enzyme active site and
      each specific inhibitor. Hydrophobic interactions, steric shape requirements, and
      hydrogen bonding of the 4-hydroxy-5,6-dihydropyrone analogues with the HIV-1
      protease binding site model dominate the RD 4D-QSAR models in a manner again
      consistent with experimental conclusions. Some possible hypotheses for the
      development of new lead HIV-1 protease inhibitors can be inferred from the RD 4D
      QSAR models.

PMID- 16426068
TI  - A two model receptor system of the alpha1D adrenergic receptor to describe
      interactions with epinephrine and BMY7378.
AB  - In this study, we have developed a two receptor model system to describe the R
      and R states of G-protein coupled receptors, specifically the alpha(1D)
      adrenergic receptor. The two models interact with agonist (epinephrine) and
      antagonist (BMY7378) differently. The active model has increased interactions
      with epinephrine. The inactive model has increased interactions with BMY7378. We
      also explored the protonation state of the ligands. When the most basic amine was
      protonated, we found increased hydrogen bonding and increased aromatic
      interactions. Protonated epinephrine hydrogen bonds with Asp176 and has aromatic
      residues Trp172, Trp235, Trp361, and Phe388 within 3 Angstroms. Protonated
      BMY7378 hydrogen bonds with Trp172 and Lys236 and has aromatic residues Trp172,
      Trp254, Phe364, Phe384, and Phe388 within 3 Angstroms. We conclude that the two
      model system is required to represent the two states of the receptor and that
      protonation of the ligand is also critical.

PMID- 16426070
TI  - Improved CoMFA modeling by optimization of settings.
AB  - The possibility of improving the predictive ability of comparative molecular
      field analysis (CoMFA) by settings optimization has been evaluated to show that
      CoMFA predictive ability can be improved. Ten different CoMFA settings are
      evaluated, producing a total of 6120 models. This method has been applied to nine
      different data sets, including the widely used benchmark steroid data set, as
      well as eight other data sets proposed as QSAR benchmarking data sets by
      Sutherland et al. (J. Med. Chem. 2004, 47, 5541-5554). All data sets have been
      studied using training and test sets to allow for both internal (q(2)) and
      external (r(2)(pred)) predictive ability assessment. CoMFA settings optimization
      was successful in developing models with improved q(2) and r(2)(pred) as compared
      to default CoMFA modeling. Optimized CoMFA is compared with comparative molecular
      similarity indices analysis (CoMSIA) and holographic quantitative structure
      activity relationship (HQSAR) models and found to consistently produce models
      with improved or equivalent q(2) and r(2)(pred). The ability of settings
      optimization to improve model predictive ability has been validated using both
      internal and external predictions, and the risk of chance correlation has been
      evaluated using response variable randomization tests.

PMID- 16426071
TI  - Screening drug-like compounds by docking to homology models: a systematic study.
AB  - In the absence of an experimentally solved structure, a homology model of a
      protein target can be used instead for virtual screening of drug candidates by
      docking and scoring. This approach poses a number of questions regarding the
      choice of the template to use in constructing the model, the accuracy of the
      screening results, and the importance of allowing for protein flexibility. The
      present study addresses such questions with compound screening calculations for
      multiple homology models of five drug targets. A central result is that docking
      to homology models frequently yields enrichments of known ligands as good as that
      obtained by docking to a crystal structure of the actual target protein.
      Interestingly, however, standard measures of the similarity of the template used
      to build the homology model to the targeted protein show little correlation with
      the effectiveness of the screening calculations, and docking to the template
      itself often is as successful as docking to the corresponding homology model.
      Treating key side chains as mobile produces a modest improvement in the results.
      The reasons for these sometimes unexpected results, and their implications for
      future methodologic development, are discussed.

PMID- 16426072
TI  - Comparison of consensus scoring strategies for evaluating computational models of
      protein-ligand complexes.
AB  - Here, the comparisons of performance of nine consensus scoring strategies, in
      which multiple scoring functions were used simultaneously to evaluate candidate
      structures for a protein-ligand complex, in combination with nine scoring
      functions (FlexX score, GOLD score, PMF score, DOCK score, ChemScore, DrugScore,
      PLP, ScreenScore, and X-Score), were carried out. The systematic naming of
      consensus scoring strategies was also proposed. Our results demonstrate that
      choosing the most appropriate type of consensus score is essential for model
      selection in computational docking; although the vote-by-number strategy was an
      effective selection method, the number-by-number and rank-by-number strategies
      were more appropriate when computational tractability was taken into account. By
      incorporating these consensus scores into the FlexX program, reasonable complex
      models can be obtained more efficiently than those selected by independent FlexX
      scores. These strategies might also improve the scoring of other docking
      programs, and more-effective structure-based drug design should result from these
      improvements.

PMID- 16426073
TI  - Development and evaluation of an in silico model for hERG binding.
AB  - It has been recognized that drug-induced QT prolongation is related to blockage
      of the human ether-a-go-go-related gene (hERG) ion channel. Therefore, it is
      prudent to evaluate the hERG binding of active compounds in early stages of drug
      discovery. In silico approaches provide an economic and quick method to screen
      for potential hERG liability. A diverse set of 90 compounds with hERG IC(50)
      inhibition data was collected from literature references. Fragment-based QSAR
      descriptors and three different statistical methods, support vector regression,
      partial least squares, and random forests, were employed to construct QSAR models
      for hERG binding affinity. Important fragment descriptors relevant to hERG
      binding affinity were identified through an efficient feature selection method
      based on sparse linear support vector regression. The support vector regression
      predictive model built upon selected fragment descriptors outperforms the other
      two statistical methods in this study, resulting in an r(2) of 0.912 and 0.848
      for the training and testing data sets, respectively. The support vector
      regression model was applied to predict hERG binding affinities of 20 in-house
      compounds belonging to three different series. The model predicted the relative
      binding affinity well for two out of three compound series. The hierarchical
      clustering and dendrogram results show that the compound series with the best
      prediction has much higher structural similarity and more neighbors of training
      compounds than the other two compound series, demonstrating the predictive scope
      of the model. The combination of a QSAR model and postprocessing analysis, such
      as clustering and visualization, provides a way to assess the confidence level of
      QSAR prediction results on the basis of similarity to the training set.

PMID- 16426074
TI  - On evaluating molecular-docking methods for pose prediction and enrichment
      factors.
AB  - Four of the most well-known, commercially available docking programs, FlexX,
      GOLD, GLIDE, and ICM, have been examined for their ligand-docking and virtual
      screening capabilities. The relative performance of the programs in reproducing
      the native ligand conformation from starting SMILES strings for 164 high
      resolution protein-ligand complexes is presented and compared. Applying only the
      native scoring functions, the latest versions of these four docking programs were
      also used to conduct virtual screening for 12 protein targets of therapeutic
      interest, involving both publicly available structures and AstraZeneca in-house
      structures. The capability of the four programs to correctly rank-order target
      specific active compounds over alternative binders and nonbinders (decoys plus
      randomly selected compounds) and thereby enrich a small subset of a screening
      library is compared. Enrichments from the virtual-screening experiments are
      contrasted with those obtained with alternative 3D shape-matching and 2D
      similarity database-search methods.

PMID- 16426075
TI  - Ensemble of linear models for predicting drug properties.
AB  - We propose a new classification method for the prediction of drug properties,
      called random feature subset boosting for linear discriminant analysis (LDA). The
      main novelty of this method is the ability to overcome the problems with
      constructing ensembles of linear discriminant models based on generalized
      eigenvectors of covariance matrices. Such linear models are popular in building
      classification-based structure-activity relationships. The introduction of
      ensembles of LDA models allows for an analysis of more complex problems than by
      using single LDA, for example, those involving multiple mechanisms of action.
      Using four data sets, we show experimentally that the method is competitive with
      other recently studied chemoinformatic methods, including support vector machines
      and models based on decision trees. We present an easy scheme for interpreting
      the model despite its apparent sophistication. We also outline theoretical
      evidence as to why, contrary to the conventional AdaBoost ensemble algorithm,
      this method is able to increase the accuracy of LDA models.

PMID- 16426076
TI  - A fully computational model for predicting percutaneous drug absorption.
AB  - The prediction of transdermal absorption for arbitrary penetrant structures has
      several important applications in the pharmaceutical industry. We propose a new
      data-driven, predictive model for skin permeability coefficients k(p) based on an
      ensemble model using k-nearest-neighbor models and ridge regression. The model
      was trained and validated with a newly assembled data set containing experimental
      data and structures for 110 compounds. On the basis of three purely computational
      descriptors (molecular weight, calculated octanol/water partition coefficient,
      and solvation free energy), we have developed a model allowing for the reliable,
      purely computational prediction of skin permeability coefficients. The model is
      both accurate and robust, as we showed in an extensive validation (correlation
      coefficient for leave-one-out cross validation: Q = 0.948, mean standard error:
      0.2 for log k(p)).

PMID- 16426077
TI  - Evaluating chemical structure similarity as an indicator of cellular growth
      inhibition.
AB  - Chemical variations of small compounds are commonly used to probe biological
      systems and potentially discover lead-like compounds with selective target
      activity. Molecular probes are either generated by synthesis or acquired through
      directed searches of commercially available compound libraries. The data
      generated when testing the probes in various biological systems constitutes a
      structure/activity analysis. The ability to detect variations and classify
      biological responses requires the analysis of a compound in multiple assays.
      While the concept of a structure/activity relationship is straightforward, its
      implementation can vary considerably depending on the biological system under
      study and the probe library selected for testing. The analysis presented here
      will focus on the accumulated compound library used to screen for growth
      inhibition across the National Cancer Institute's panel of 60 tumor cells. The
      considerable chemical and biological diversity inherent in these data offers an
      opportunity to establish a quantifiable connection between chemical structure and
      biological activity. We find that the connection between structure and biological
      response is not symmetric, with biological response better at predicting chemical
      structure than vice versa. Structurally and functionally similar compounds can
      have distinguishable biological responses reflecting different mechanisms of
      action.

PMID- 16426078
TI  - On updating torsion angles of molecular conformations.
AB  - A conformation of a molecule is defined by the relative positions of atoms and by
      the chirality of asymmetric atoms in the molecule. The three main representations
      for conformations of molecules are Cartesian coordinates, a distance geometry
      descriptor (which consists of a distance matrix and the signs of the volumes of
      quadruples of atoms), and internal coordinates. In biochemistry, conformational
      changes of a molecule are usually described in terms of internal coordinates.
      However, for many applications, such as molecular docking, the Cartesian
      coordinates of atoms are needed for computation. Although, for each
      conformational change, the Cartesian coordinates of atoms can be updated in
      linear time (which is optimal asymptotically), the constant factor becomes
      significant if a large number of updates are needed. Zhang and Kavraki (J. Chem.
      Inf. Comput. Sci. 2002, 42, 64-70) examined three methods: the simple rotations,
      the Denavit-Hartenberg local frames, and the atom-group local frames. On the
      basis of their implementations, they showed that the atom-group local frames are
      more efficient than the other two. In this paper, by expressing the torsion-angle
      change as a composition of translations and rotations, we observe that the simple
      rotations can be implemented in an efficient way by taking advantage of
      consecutive operations. Both quantitative and experimental comparisons show that
      the improved simple rotations, in which rotations are expressed in unit
      quaternions, are as efficient as the atom-group local frames and, thus, have the
      advantage of avoiding the need of precomputations of a set of local frames and
      transformations between them.

PMID- 16426079
TI  - PEARLS: program for energetic analysis of receptor-ligand system.
AB  - Analysis of the energetics of small molecule ligand-protein, ligand-nucleic acid,
      and protein-nucleic acid interactions facilitates the quantitative understanding
      of molecular interactions that regulate the function and conformation of
      proteins. It has also been extensively used for ranking potential new ligands in
      virtual drug screening. We developed a Web-based software, PEARLS (Program for
      Energetic Analysis of Ligand-Receptor Systems), for computing interaction
      energies of ligand-protein, ligand-nucleic acid, protein-nucleic acid, and ligand
      protein-nucleic acid complexes from their 3D structures. AMBER molecular force
      field, Morse potential, and empirical energy functions are used to compute the
      van der Waals, electrostatic, hydrogen bond, metal-ligand bonding, and water
      mediated hydrogen bond energies between the binding molecules. The change in the
      solvation free energy of molecular binding is estimated by using an empirical
      solvation free energy model. Contribution from ligand conformational entropy
      change is also estimated by a simple model. The computed free energy for a number
      of PDB ligand-receptor complexes were studied and compared to experimental
      binding affinity. A substantial degree of correlation between the computed free
      energy and experimental binding affinity was found, which suggests that PEARLS
      may be useful in facilitating energetic analysis of ligand-protein, ligand
      nucleic acid, and protein-nucleic acid interactions. PEARLS can be accessed at
      http://ang.cz3.nus.edu.sg/cgi-bin/prog/rune.pl.

PMID- 16426080
TI  - Photobleaching of reduced nicotinamide adenine dinucleotide and the development
      of highly fluorescent lesions in rat basophilic leukemia cells during multiphoton
      microscopy.
AB  - Endogenous reduced nicotinamide adenine dinucleotide (NADH) fluorescence provides
      an intrinsic indicator of the cellular metabolic state, but prolonged monitoring
      is limited by photobleaching and/or phototoxicity. Multiphoton excitation of NADH
      by ultrashort, 740-nm laser pulses provides a significant improvement over UV
      excitation by eliminating peripheral photobleaching; however, molecules within
      the subfemtoliter excitation volume remain susceptible. We have investigated the
      photophysical mechanisms responsible for multiphoton photobleaching of NADH in
      living cells to permit the imaging technique to be optimized. The loss of
      fluorescence because of multiphoton photobleaching was measured by repetitively
      imaging individual planes within rat basophilic leukemia cells. The
      photobleaching rate was proportional to the fourth power of the laser intensity.
      Based on these measurements, we propose a double-biphotonic, four-photon
      photobleaching mechanism and estimate the quantum yield of photobleaching of
      intracellular NADH to be 0.0073 +/- 0.0002 by this mechanism. In addition to
      photobleaching, the development of bright, punctate fluorescent lesions can also
      be observed. The frequency of lesion formation also increased approximately as
      the fourth power of the laser intensity after an intensity-dependent threshold
      number of images had been exceeded. The consequences for two-photon metabolic
      imaging are discussed.

PMID- 16426081
TI  - Focus on Childhood and Adolescent Mental Health.

PMID- 16426082
TI  - The impact of disasters and their aftermath on mental health.

PMID- 16426083
TI  - High-dose sertraline strategy for nonresponders to acute treatment for obsessive
      compulsive disorder: a multicenter double-blind trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of high-dose sertraline for
      patients with obsessive-compulsive disorder (OCD) who failed to respond to
      standard sertraline acute treatment. METHOD: Sixty-six nonresponders to 16 weeks
      of sertraline treatment who met DSM-III-R criteria for current OCD were randomly
      assigned, in a double-blind continuation phase of a multicenter trial, either to
      continue on 200 mg/day of sertraline or to increase their dose to between 250 and
      400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown
      Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health
      Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global
      Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were
      collected from July 26, 1994, to October 26, 1995. RESULTS: The high-dose (250
      400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly
      greater symptom improvement than the 200-mg/day group (N = 36) as measured by the
      YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011).
      Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or =
      3) were not significantly different for the 200-mg/day versus the high-dose
      sertraline group, either on completer analysis, 34% versus 52%, or on endpoint
      analysis, 33% versus 40%. Both treatments showed similar adverse event rates.
      CONCLUSION: Greater symptom improvement was seen in the high-dose sertraline
      group compared to the 200-mg/day dose group during continuation treatment. Both
      dosages yielded similar safety profiles. Administration of higher than labeled
      doses of selective serotonin reuptake inhibitors may be a treatment option for
      certain OCD patients who fail to respond to standard acute treatment.

PMID- 16426084
TI  - Prevalence and severity of intimate partner violence and associations with family
      functioning and alcohol abuse in psychiatric inpatients with suicidal intent.
AB  - BACKGROUND: Many medical settings have conducted screenings for domestic
      violence, but no study has assessed the prevalence and frequency of intimate
      partner violence (IPV) within the acute psychiatric inpatient population. METHOD:
      This descriptive, cross-sectional study was conducted in adult inpatient acute
      care units at a psychiatric hospital. Participants completed questionnaire-based
      assessments of recent and lifetime history of IPV, family functioning, and
      alcohol use. Recruited patients were aged between 18 and 65 years, were English
      fluent and literate, had suicidal ideation, and had been living with an intimate
      partner for at least the past 6 months. Acutely psychotic patients and patients
      who were too agitated to complete the questionnaires were excluded. 110 patients
      completed the assessments. Interpersonal violence was assessed using the Revised
      Conflict Tactics Scale (CTS2), family functioning was measured using the Family
      Assessment Device, and alcohol use was assessed with the Alcohol Use Disorders
      Identification Test. Data were gathered from August 2004 through February 2005.
      RESULTS: Over 90% of suicidal inpatients reported IPV perpetration and
      victimization in their relationships in the past year, with the overwhelming
      majority reporting severe IPV. Male and female patients did not differ
      significantly on any CTS2 violence perpetration or victimization subscale (all p
      values >.05). Poor family functioning predicted physical violence victimization
      in both male and female suicidal inpatients, even after controlling for alcohol
      use and demographic characteristics. CONCLUSION: Psychiatric inpatients with
      suicidal ideation or intent would benefit from screening for IPV. Information
      about IPV and treatment options should be made available to psychiatric
      inpatients with suicidal intent. Attention to the family functioning of these
      patients is recommended.

PMID- 16426085
TI  - Botulinum toxin treatment of social anxiety disorder with hyperhidrosis: a
      placebo-controlled double-blind trial.
AB  - OBJECTIVE: Given the often prominent and persistent nature of hyperhidrosis in
      social anxiety disorder (SAD), to compare botulinum toxin type A to placebo for
      generalized SAD with hyperhidrosis, in combination with paroxetine. METHOD:
      Adults with severe axillary hyperhidrosis who met DSM-IV criteria for generalized
      SAD were randomly assigned to receive 1-time, bilateral, intradermal injections
      with either botulinum toxin type A or placebo (50 units/axilla). All subjects
      also received 8 weeks of open-label treatment with paroxetine. The primary
      outcome measure was the Hyperhidrosis Disease Severity Scale (HDSS). Secondary
      measures included the Hyperhidrosis Impact Questionnaire, Brief Social Phobia
      Scale, Liebowitz Social Anxiety Scale, Social Phobia Inventory, and Sheehan
      Disability Scale. Enrollment occurred from June 2002 to July 2004. RESULTS: Forty
      subjects were randomly assigned to treatment and included in the analyses.
      Response rates were 75% (15/20) for botulinum toxin type A versus 15% (3/20) for
      placebo on the HDSS (p < .001). Botulinum toxin type A produced significantly
      more improvement in many daily activities that had been limited (p < .01), as
      well as greater improvement in work and social functioning and in overall
      disability (p < .05). Botulinum toxin type A was well tolerated, as was
      paroxetine. CONCLUSION: Botulinum toxin is effective in reducing hyperhidrosis
      disability and limitations in everyday activities when given in association with
      paroxetine to subjects with SAD. While further assessment of botulinum toxin type
      A in SAD is recommended, including a trial of botulinum toxin type A monotherapy,
      the results suggest that this well-tolerated treatment deserves further
      consideration in overall management of SAD accompanied by hyperhidrosis.

PMID- 16426086
TI  - Validity of the impact factor of journals as a measure of randomized controlled
      trial quality.
AB  - OBJECTIVE: To assess whether the impact factor, a measure of the frequency with
      which journal articles are cited in the scientific literature, is a proxy measure
      of the quality of articles reporting the results of randomized controlled trials.
      METHOD: The quality of trials included in an ongoing Cochrane review concerned
      with the antidepressant fluoxetine was assessed using the Cochrane Collaboration
      Depression, Anxiety, and Neurosis quality assessment instrument, the Jadad scale,
      and the quality criterion of the Cochrane Collaboration Handbook. Journal impact
      factors were extracted from the Journal Citation Report. RESULTS: A total of 131
      articles reported results from 132 clinical trials comparing fluoxetine with
      other antidepressants. The relationship between trial quality and the impact
      factor of journals where these studies were published, stratified by period of
      publication, revealed that journals with impact factors above 4 points published
      only trials with above-average overall quality ratings, while journals with
      impact factors below 4 points published both high- and low-quality trials. The
      Jadad scale revealed similar quality in trials published in journals with high,
      medium, and low impact factors (Pearson chi(2) = 0.298, p = .861), and the
      quality criterion of the Cochrane Collaboration Handbook showed unclear
      randomization in the majority of trials and in all 15 trials published in high
      impact factor journals (Pearson chi(2) = 4.678, p = .096). CONCLUSION: The impact
      factor of journals is not a valid measure of randomized controlled trial quality.

PMID- 16426087
TI  - Remission of generalized anxiety disorder: a review of the paroxetine clinical
      trials database.
AB  - OBJECTIVE: Paroxetine is a potent selective serotonin reuptake inhibitor with
      antidepressant and anxiolytic activity that is effective in the treatment of
      generalized anxiety disorder (GAD), improving the core symptoms of anxiety,
      worry, and tension. The majority of patients with GAD have chronic symptomatology
      and significant comorbid mood and anxiety disorders that often require ongoing
      pharmacotherapy. This article reviews the efficacy and tolerability of paroxetine
      in the short- and long-term treatment of GAD including remission data. DATA
      SOURCES: Data from more than 1800 outpatients with DSM-IV-defined GAD were
      analyzed from 3 short-term (8-week) studies and a longer (6-month) relapse
      prevention study. These studies were all randomized, double-blind, placebo
      controlled trials of paroxetine. DATA SYNTHESIS: The results emphasize the
      benefit of paroxetine treatment in GAD, enabling a substantial proportion of
      patients to achieve clinical remission and preventing relapse. Long-term
      treatment with paroxetine also shows good tolerability with no evidence of weight
      gain. CONCLUSION: Given the high comorbidity of psychiatric depression and
      anxiety, the long-term efficacy and tolerability of paroxetine are important
      considerations when selecting a first-line therapy for patients with GAD.

PMID- 16426088
TI  - Are antidepressants associated with new-onset suicidality in bipolar disorder? A
      prospective study of participants in the Systematic Treatment Enhancement Program
      for Bipolar Disorder (STEP-BD).
AB  - OBJECTIVE: Depressive episodes are common in bipolar disorder, and the disorder
      is characterized by high suicide rates. Recent analyses indicate a possible
      association of antidepressant treatment and suicidality in children and adults
      with depressive or anxiety disorders. However, few data are available to inform
      the suicidality risk assessment of antidepressant use specifically in bipolar
      disorder. METHOD: Of the first 2000 participants followed for 18 months in the
      Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), 425
      experienced a prospectively observed, new-onset major depressive episode without
      initial suicidal ideation. Standardized ratings of suicidality and antidepressant
      exposure at index depressive episode and next evaluation were used to investigate
      the primary hypothesis that new-onset suicidality was associated with increased
      antidepressant exposure (antidepressant initiation or dose increase). Secondary
      analysis investigated correlates of new-onset suicidality and antidepressant
      exposure. Data were collected from November 8, 1999, to April 24, 2002. RESULTS:
      Twenty-four participants (5.6%) developed new-onset suicidality at follow-up,
      including 2 suicide attempts. There was no association of new-onset suicidality
      with increased antidepressant exposure or any change in antidepressant exposure,
      and no association with initiation of antidepressant treatment. New-onset
      suicidality was associated with neuroticism, prior attempt, and higher depressive
      or manic symptom ratings at index episode. Increased antidepressant exposure was
      negatively associated with higher manic symptom rating at index episode; control
      for this sole empirically identified confound did not alter the primary results.
      CONCLUSIONS: Although careful monitoring for suicidality is always warranted in
      bipolar disorder, this cohort study provides no evidence that increased
      antidepressant exposure is associated with new-onset suicidality in this already
      high-risk population. Correlates of both suicidality and antidepressant exposure
      indicate directions for further research.

PMID- 16426089
TI  - Nativity and DSM-IV psychiatric disorders among Puerto Ricans, Cuban Americans,
      and non-Latino Whites in the United States: results from the National
      Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: This study examined the risk of lifetime substance use disorders and
      mood and anxiety disorders between Island-born Puerto Ricans, foreign-born Cuban
      Americans, and foreign-born non-Latino whites and their U.S.-born counterparts.
      METHOD: Data from the 2001-2002 National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC; N = 43,093) were used to derive lifetime prevalence
      rates of specific DSM-IV psychiatric disorders by subethnicity and nativity
      group. Logistic regression models were constructed to detect variation in the
      odds of each psychiatric disorder across groups. RESULTS: A protective effect of
      foreign-born nativity in risk for psychiatric disorders was present for all
      groups but varied according to the assessed disorder. For non-Latino whites, the
      effect was observed for most specific psychiatric disorders, whereas, for Puerto
      Ricans and Cuban Americans, the effect was only evident for specific substance
      use disorders. CONCLUSION: The protective effect of nativity against psychiatric
      morbidity found in other studies among Mexican Americans and non-Latino whites
      does not entirely generalize to Puerto Ricans and Cuban Americans and may not
      generalize to individuals of other origins. The results of this study are
      discussed in terms of potential mechanisms involved in variations in the risk of
      specific psychiatric disorders among groups defined by nativity and race
      ethnicity and the importance of identifying specific cultural components that may
      serve as risk and protective factors of psychiatric morbidity.

PMID- 16426090
TI  - Open-label tiagabine monotherapy for major depressive disorder with anxiety.
AB  - OBJECTIVE: Gamma-aminobutyric acid (GABA) plays a key role in the pathophysiology
      and treatment of depression and anxiety. Tiagabine, a selective GABA reuptake
      inhibitor (SGRI) that enhances normal GABA tone, was evaluated for its efficacy
      and safety in the treatment of depression comorbid with significant anxiety.
      METHOD: In this 8-week, single-center, open-label study, adults with DSM-IV
      diagnosed major depressive disorder and significant anxiety (i.e., "anxious
      depression") received tiagabine monotherapy, initiated at 4 mg/day and titrated
      for optimum response as tolerated to a maximum dose of 20 mg/day. Symptoms,
      function, and adverse events were assessed at regular intervals. Patients were
      entered from April 2002 to February 2003. RESULTS: Nineteen patients entered the
      study and 15 met criteria for intent-to-treat analyses. Of those, 6 (40%)
      discontinued treatment and 9 (60%) completed the 8-week protocol. Tiagabine
      significantly improved depression, as shown by a reduction in mean +/- SD
      Hamilton Rating Scale for Depression scores from baseline (31.9 +/- 6.1) to
      endpoint (17.0 +/- 12.4; p = .002). Categorical response rate was 47% (N = 7).
      Tiagabine also significantly improved anxiety (Hamilton Rating Scale for Anxiety
      baseline score of 22.7 +/- 4.9 vs. endpoint score of 12.5 +/- 8.8; p = .002). The
      mean +/- SD final daily dose was 12.8 +/- 5.8 mg. The most commonly reported
      adverse events were dizziness, headache, and gastrointestinal upset/nausea.
      CONCLUSION: These results suggest the potential of the SGRI tiagabine in the
      treatment of depression with anxiety. Large, placebo-controlled trials are
      needed.

PMID- 16426091
TI  - Venlafaxine extended release in the short-term treatment of depressed and anxious
      primary care patients with multisomatoform disorder.
AB  - OBJECTIVE: This pilot study explored the efficacy and tolerability of extended
      release venlafaxine (venlafaxine ER) in anxious and/or depressed patients with
      multisomatoform disorder (MSD). METHOD: This 12-week, multicenter, randomized,
      double-blind study evaluated adult primary care outpatients with MSD and comorbid
      major depressive disorder, generalized anxiety disorder, or social anxiety
      disorder (DSM-IV criteria). The intent-to-treat population included 112 patients
      (venlafaxine ER, N = 55; placebo, N = 57). The primary efficacy variable was the
      change in the 15-item Patient Health Questionnaire (PHQ-15) somatic symptom
      severity score. Secondary outcomes included the Hamilton Rating Scale for
      Depression (HAM-D-17) and for Anxiety (HAM-A), Clinical Global Impressions
      Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, McGill Quality of
      Life Questionnaire Physical Symptoms Scale (MQOL-PS), and Medical Outcomes Study
      Short-Form 36-Item questionnaire (MOS SF-36). Data were collected from April 2003
      to December 2003. RESULTS: The decline by week 12 in PHQ-15 scores was
      significant (p < .0001) in both groups; however, the difference between the
      venlafaxine ER and placebo groups (-8.3 vs. -6.6, respectively) was not (p =
      .097). Improvement was greater with venlafaxine ER than placebo on the PHQ-15
      pain subscale (p = .03), SF-36 bodily pain scale (26.1 vs. 14.5, p = .03), MQOL
      PS (-11.7 vs. -6.0, p = .02), HAM-A psychic anxiety subscale (p = .02), SF-36
      mental component summary (p = .03), time to response (54 vs. 71 days, p = .01),
      and CGI-I scale (p = .009). Venlafaxine ER was generally well tolerated.
      CONCLUSION: These results suggest that venlafaxine ER may be effective in
      relieving some types of somatic physical symptoms, particularly pain, in patients
      with depression and/or anxiety disorders.

PMID- 16426092
TI  - An open trial of adjunctive escitalopram in bipolar depression.
AB  - OBJECTIVE: This study was designed to evaluate the efficacy and safety of a
      highly potent and selective serotonergic antidepressant, escitalopram, in the
      treatment of bipolar depression. METHOD: Twenty outpatients with DSM-IV bipolar
      depression types I and II were enrolled in a 12-week open trial of escitalopram,
      10 mg daily, adjunctive to their ongoing mood stabilizer. Assessments were
      carried out using the Hamilton Rating Scale for Depression (HAM-D), the Young
      Mania Rating Scale (YMRS), and the Clinical Global Impressions for Severity (CGI
      S) and Improvement (CGI-I) scales. The study was conducted from August 2003 to
      February 2004. RESULTS: Escitalopram was associated with significant improvement
      as measured by the HAM-D total score, which showed a mean reduction from baseline
      (mean = 20.9, SD = 4.2) to endpoint (mean = 8.9, SD = 3.6; p < .001) of 12
      points. The mean CGI-S score decreased by 3.3 points (baseline: mean = 4.8, SD =
      0.7; week 12: mean = 1.5, SD = 0.6; p < .001). Adverse events emerged in 75% of
      the patients (N = 15), usually of mild-to-moderate severity. Four dropouts took
      place due to manic switch (N = 1), hypomanic symptoms (N = 2), and
      hospitalization due to the emergence of suicidal ideation and psychosis (N = 1).
      CONCLUSION: These findings suggest that escitalopram in association with mood
      stabilizers may be an effective and reasonably well-tolerated treatment for
      patients with moderate-to-severe bipolar depression. The switch rate was similar
      to what is described in the literature for the selective serotonin reuptake
      inhibitors. Randomized controlled trials of escitalopram in bipolar depression
      are warranted.

PMID- 16426093
TI  - Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS)
      in males: newly described fronto-subcortical dementia.
AB  - OBJECTIVE: The authors describe and quantify the neuropsychiatric symptoms
      present in a cohort of males with the fragile X mental retardation 1 (FMR1)
      premutation allele who have developed fragile X-associated tremor/ataxia syndrome
      (FXTAS). METHOD: Fourteen male carriers of the FMR1 premutation who had clinical
      manifestations of the FXTAS syndrome and 14 age- and education-matched controls
      were assessed with the Neuropsychiatric Inventory (NPI), formal cognitive
      testing, and genetic analysis. RESULTS: Males with FXTAS had significantly higher
      total NPI scores (p < .004) and significantly higher scores on the
      agitation/aggression (p < .004), depression (p < .004), apathy (p < .004),
      disinhibition (p < .004), and irritability (p < .004) scales, compared with
      controls. Cognitive performances on the Mini-Mental State Examination did not
      correlate with severity of symptoms on the NPI. CONCLUSIONS: The neuropsychiatric
      manifestations of FXTAS, based on this preliminary report, appear to cluster as a
      fronto-subcortical dementia. Clinicians encountering patients with clinical
      dementia with motor symptoms suggesting FXTAS should consider genetic testing to
      determine whether the patient's dementia syndrome is secondary to a fragile X
      premutation carrier status.

PMID- 16426094
TI  - Differential efficacy of olanzapine and lithium in preventing manic or mixed
      recurrence in patients with bipolar I disorder based on number of previous manic
      or mixed episodes.
AB  - INTRODUCTION: Bipolar disorder outcome worsens as number of manic episodes
      increases, suggesting that prevention of recurrent episodes early during the
      disorder could improve patient prognosis. We investigated treatment efficacy in
      prevention of mood episodes in patients subgrouped by number of prior manic
      episodes. METHOD: This study was a post hoc analysis of data from a multicenter,
      double-blind, 12-month clinical trial of relapse/recurrence in 431 initially
      euthymic patients with at least 2 prior manic/ mixed episodes and a DSM-IV
      diagnosis of bipolar I disorder randomly assigned to olanzapine (5-20 mg/day) or
      lithium (serum concentration 0.6 to 1.2 mEq/L). Data were collected between
      August 1999 and June 2002. Patients were subcategorized by illness stage
      according to number of prior manic/mixed episodes-early stage: 2 prior episodes
      (N = 53, lithium; N = 48, olanzapine), intermediate stage: 3 to 5 prior episodes
      (N = 80, lithium; N = 98, olanzapine), and later stage: more than 5 prior
      episodes (N = 81, lithium; N = 71, olanzapine)-and were evaluated for rates of
      relapse/recurrence. RESULTS: There were significant effects for treatment (p <
      .001) and illness stage (p = .006) but no significant interaction (p = .107) on
      rate of manic/mixed relapse/recurrence. Rates of manic/ mixed relapse/recurrence
      for olanzapine versus lithium were 2.1% versus 26.4% (p = .008), 13.3% versus
      23.8% (p = .073), and 23.9% versus 33.3% (p = .204) for early-, intermediate-,
      and later-stage groups, respectively. There was no significant effect for
      treatment (p = .096) or illness stage (p = .731) for depressive
      relapse/recurrence. CONCLUSIONS: Early-stage (but not intermediate-or later
      stage) patients had a significantly lower rate of relapse/recurrence of
      manic/mixed episodes with olanzapine compared to lithium. Thus, olanzapine
      maintenance therapy may be particularly effective early in the course of bipolar
      illness.

PMID- 16426095
TI  - The association between moderate alcohol use and illness severity in bipolar
      disorder: a preliminary report.
AB  - OBJECTIVE: To examine the association of alcohol consumption with symptoms,
      illness course, and health care utilization among non-alcoholic patients with
      bipolar disorder. METHOD: Subjects were 148 patients with bipolar I or II
      disorder enrolled in a longitudinal study of cognitive-behavioral therapy versus
      psychoeducation. Subjects were 18 to 60 years old, in full or partial remission,
      and non-heavy drinkers with no history of substance use disorders. At least 4
      weeks of consistent naturalistic treatment with mood stabilizer was required for
      enrollment. Measures included the Structured Clinical Interview for DSM-IV, the
      Hamilton Rating Scale for Depression, the Clinician-Administered Rating Scale for
      Mania, and the Khavari Alcohol Test. Data were gathered from July 2002 to
      December 2004. RESULTS: Mean weekly alcoholic beverage consumption was minimal
      among both men (3.8 standard drinks, SD = 8.9) and women (1.2 standard drinks, SD
      = 1.9). Nonetheless, total alcohol consumption among men was associated with
      lifetime manic episodes (F = 10.2, df = 1, p = .003) and emergency department
      visits (F = 4.3, df = 1, p = .046). Spirits consumption among men was strongly
      associated with lifetime manic episodes (F = 81.8, df = 1, p < .001) and
      emergency department visits (F = 14.0, df = 1, p < .001). Among women, the
      frequency of alcohol consumption was associated with lifetime episodes of
      depression (F = 15.5, df = 1, p < .001) and hypomania (F = 4.8, df = 1, p < .03).
      Wine consumption among women was associated with lifetime hypomanic episodes (F =
      13.6, df = 1, p < .001) and current manic symptoms (F = 4.0, df = 1, p < .05).
      CONCLUSION: Despite low volumes of consumption, alcohol was associated with
      measures of illness severity in bipolar disorder among both men and women. The
      adverse effects of alcohol on bipolar disorder may occur over a range of
      consumption, rather than being confined to heavy drinkers.

PMID- 16426096
TI  - Comparison of treatment-emergent extrapyramidal symptoms in patients with bipolar
      mania or schizophrenia during olanzapine clinical trials.
AB  - BACKGROUND: Previous research on pharmacotherapy with conventional antipsychotics
      has suggested that patients with affective disorders have higher rates of
      treatment-emergent extrapyramidal symptoms (EPS) than patients with
      schizophrenia. It is not known whether this differential vulnerability holds true
      for treatment with atypical antipsychotics such as olanzapine. The present
      analysis retrospectively examined olanzapine clinical trial data for incidence of
      treatment-emergent EPS in patients with either schizophrenia or bipolar disorder.
      METHOD: Study participants were 4417 patients meeting DSM-III or DSM-IV criteria
      for either schizophrenia or bipolar mania participating in olanzapine clinical
      trials through July 31, 2001. Data were pooled across haloperidol-controlled
      trials and separately across placebo-controlled trials. Measures of EPS included
      rates of treatment-emergent EPS adverse event by type (i.e., dystonic,
      parkinsonian, or residual), Simpson-Angus Scale score mean change, rates of
      treatment-emergent parkinsonism, and rates of anticholinergic use. RESULTS:
      Consistent with prior research, haloperidol-treated patients with bipolar
      disorder appeared to be more vulnerable to the development of EPS than those with
      schizophrenia. However, olanzapine-treated patients with bipolar disorder were no
      more likely to develop EPS than those with schizophrenia. CONCLUSION: Results
      support previous research regarding conventional antipsychotics and suggest that
      olanzapine therapy does not increase the risk of EPS for patients with bipolar
      disorder.

PMID- 16426098
TI  - The health care crisis of childhood-onset bipolar illness: some recommendations
      for its amelioration.
AB  - OBJECTIVE: To describe new data on the incidence and impact of childhood- and
      adolescent-onset bipolar illness and make recommendations to help accelerate the
      acquisition of knowledge in this area. DATA SOURCES: Two large, multicenter out
      patient studies in adults with DSM-IV bipolar disorder-the Systematic Treatment
      Enhancement Program for Bipolar Disorder and the Bipolar Collaborative Network
      were the primary sources of retrospective data on age at onset. STUDY SELECTION:
      We focused on the 2 retrospective studies because they supplied more immediate
      data on age at onset and long-term prognosis than current prospective studies.
      DATA SYNTHESIS: The 2 studies revealed that 15% to 28% of adults experienced an
      onset of their illness prior to age 13 years. Those with childhood versus adult
      onset had a more severe, complicated, and adverse course of bipolar illness,
      assessed retrospectively and confirmed prospectively during naturalistic
      treatment. The time lag from onset of first symptoms to first treatment was
      strongly inversely related to age at onset and averaged 16.8 +/- 10 years in
      those with childhood onset. Recommendations include defining temporary consensus
      threshold criteria for each bipolar subtype and their prodromes; conducting
      studies using less onerous than traditional designs, including randomized open
      comparisons to acquire preliminary data in this age cohort; and forming clinical
      and academic treatment outcome networks to more quickly acquire treatment outcome
      data in this understudied population. CONCLUSIONS: The data reveal a very
      substantial rate of childhood-onset bipolar illness, extraordinary delays in
      onset to first treatment, and a very adverse long-term outcome. Several
      approaches to accelerating the rate of acquisition of treatment outcome data in
      this cohort are outlined.

PMID- 16426099
TI  - Children of currently depressed mothers: a STAR*D ancillary study.
AB  - OBJECTIVE: To assess the current and lifetime prevalence of psychiatric disorders
      among children of currently depressed mothers and to assess the association of
      clinical features of maternal depression (i.e., severity, chronicity, and
      clinical features) with child psychopathology. Mothers were participants in the
      STAR*D (Sequenced Treatment Alternatives to Relieve Depression) multisite trial,
      designed to compare effectiveness and acceptability of different treatment
      options for outpatients with non-psychotic major depressive disorder (MDD).
      METHOD: Treatment-seeking mothers with a current DSM-IV diagnosis of MDD and with
      at least 1 child 7 to 17 years old were assessed during a major depressive
      episode (MDE). For each mother, 1 child was assessed (if a mother had more than 1
      child, 1 was randomly selected). Maternal features assessed for this study were
      history of MDEs, severity of current MDE, comorbid conditions, depressive symptom
      features, and social functioning. Children were assessed for selected psychiatric
      diagnoses (Schedule for Affective Disorders and Schizophrenia for School-Age
      Children-Present and Lifetime Version [K-SADS-PL]), psychopathologic symptoms and
      social functioning (Child Behavior Checklist), and global functioning (Children's
      Global Assessment Scale). Data were gathered from December 2001 to April 2004.
      RESULTS: A large proportion (72%) of mothers were severely depressed (17-item
      Hamilton Rating Scale for Depression score >/= 22). About a third (34%) of
      children had a current psychiatric disorder, including disruptive behavior (22%),
      anxiety (16%), and depressive (10%) disorders. Nearly half (45%) had a lifetime
      psychiatric disorder, including disruptive behavior (29%), anxiety (20%), and
      depressive (19%) disorders. Atypical depressive features in the mother were
      associated with a 3-fold increase in the odds of having a child with depressive
      (OR = 3.3 [95% CI = 1.2 to 9.5]; p = .02) or anxiety (OR = 2.6 [95% CI = 1.1 to
      6.9]; p = .03) disorders. A history of maternal suicide attempts and the presence
      of comorbid panic disorder with agoraphobia were associated with a 3-fold
      increase and an 8-fold increase in the odds of depressive disorders in the
      offspring, respectively. The final model showed significant associations (p </=
      .05) between the following characteristics of maternal depression and offspring
      disorders: maternal comorbid panic disorder with agoraphobia and offspring
      depressive and anxiety disorders, maternal irritable depression and offspring
      disruptive behavior disorders and any disorder, and maternal substance use
      disorders and any disorder. CONCLUSIONS: Children of mothers in the midst of a
      current MDE are at high risk for disruptive behavior and anxiety disorders. The
      elevated risk of psychopathology among children of depressed mothers may
      recommend assessment of these children when clinically suggested. Children of
      depressed mothers with comorbid panic disorder with agoraphobia are at high risk
      for depressive and anxiety disorders and deserve special attention from
      clinicians.

PMID- 16426100
TI  - Modafinil film-coated tablets in children and adolescents with attention
      deficit/hyperactivity disorder: results of a randomized, double-blind, placebo
      controlled, fixed-dose study followed by abrupt discontinuation.
AB  - OBJECTIVE: The objective of this fixed-dose study was to determine the efficacy
      and safety of a new formulation of modafinil (modafinil film-coated tablets) in
      children and adolescents with attention-deficit/hyperactivity disorder (ADHD). In
      addition, the effect of abrupt discontinuation of modafinil was evaluated in a 2
      week observation period. METHOD: Patients aged 6 to 17 years with DSM-IV-TR
      defined ADHD were randomly assigned to 7 weeks of double-blind treatment with
      modafinil or placebo in a 2:1 ratio, followed by abrupt discontinuation of
      modafinil and a 2-week, double-blind observation period in which 46% of patients
      receiving modafinil were switched to placebo without tapering and half continued
      to receive modafinil. Study drug was administered once daily and titrated over
      the first 7 to 9 days to daily doses of 340 mg for patients < 30 kg or 425 mg for
      patients > or = 30 kg. Assessment instruments included the Attention-Deficit/
      Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions and
      Clinical Global Impressions-Improvement scale (CGI-I). The study was conducted
      from November 2003 to June 2004. RESULTS: A total of 190 patients were randomly
      assigned to receive modafinil (340 mg, N = 44; 425 mg, N = 82) or placebo (N =
      64). 189 patients were evaluated for safety. Modafinil significantly improved
      symptoms of ADHD as shown by reductions in ADHD-RS-IV School Version total scores
      compared with placebo at all visits (p < or = .009), including the final visit of
      the double-blind phase (p < .0001). With modafinil, ADHD-RS-IV School Version
      mean total scores changed from 37.8 at baseline to 29.3 at week 1 and 20.7 at
      final visit; corresponding placebo values were 36.6, 32.8, and 28.4,
      respectively; effect size at final visit was 0.76 (95% CI = 0.63 to 0.88). Total
      scores on the ADHD-RS-IV Home Version were also significantly reduced at all
      visits (p < or = .022) and final visit (p = .001) in patients receiving modafinil
      compared with those receiving placebo. Significantly higher proportions of
      patients receiving modafinil were rated "much improved" or "very much improved"
      in overall clinical condition (CGI-I) at all visits compared with patients
      receiving placebo (p < .001). No withdrawal symptoms were observed when modafinil
      was abruptly discontinued at the beginning of the final 2-week observation
      period. Modafinil was generally well tolerated. Insomnia, headache, and decreased
      appetite were the most commonly reported adverse events. Sixty-three percent of
      patients who received modafinil completed the study; 13% discontinued because of
      lack of efficacy; 10%, because of adverse events; and 13%, for other reasons
      (e.g., consent withdrawn, lost to follow-up). CONCLUSION: Modafinil significantly
      improved symptoms of ADHD both at school and at home and was well tolerated by
      children and adolescents. Abrupt discontinuation of modafinil was not associated
      with symptoms of withdrawal or with rebound of symptoms of ADHD.

PMID- 16426101
TI  - New developments in the treatment of ADHD.

PMID- 16426102
TI  - Real-life switching strategies with second-generation antipsychotics.

PMID- 16426103
TI  - Methodological issues in a comparative study of ziprasidone and risperidone.

PMID- 16426106
TI  - Methodological concerns regarding the relation between mefloquine and serious
      psychiatric events in females.

PMID- 16426107
TI  - Propofol for severe, refractory mania: a case report.

PMID- 16426108
TI  - Galantamine-induced QTc prolongation.

PMID- 16426109
TI  - Introduction: an overview of the issues surrounding the recognition and
      management of bipolar disorder and comorbid anxiety.

PMID- 16426110
TI  - Prevalence and impact of comorbid anxiety and bipolar disorder.
AB  - Comorbid conditions pose a serious risk to patients with bipolar disorder, but
      anxiety comorbidity poses a specific hazard due to the increased negative impact
      of anxiety on illness course and treatment. Anxiety comorbidity appears to be
      highly prevalent and is associated with intensified symptoms of bipolar disorder
      and additional comorbid disorders, resulting in a negative impact on the patient
      and on the course of the illness. The presence of anxiety in bipolar patients is
      also associated with a lowered age at onset, hampered patient response to
      treatment such as lithium, increased rates of suicide and substance abuse, and
      decreased quality of life. Patients can experience work, family, and social
      impairment and be made to contend with increased health care costs and strains on
      family support. Studies are few and have a limited scope, and many have failed to
      consider the clinical significance of comorbid anxiety and bipolar disorder.
      Because the degree to which anxiety impacts patients with bipolar disorder is not
      fully known, more information is needed about the relationship between bipolar
      disorder and anxiety.

PMID- 16426111
TI  - Pharmacologic treatment considerations in co-occurring bipolar and anxiety
      disorders.
AB  - BACKGROUND: Anxiety disorders are among the most commonly co-occurring
      psychiatric syndromes with bipolar disorder. The presence of co-occurring anxiety
      disorders has important prognostic and treatment implications. METHOD: Using the
      PaperChase database augmented by a manual search of the literature, we identified
      122 publications that consisted of reports regarding pharmacologic agents used in
      the treatment of bipolar disorder also assessing the efficacy of these agents in
      anxiety disorders, treatment studies of patients with comorbid bipolar disorder
      and specific anxiety disorders, and studies of novel antiepileptic agents in the
      treatment of anxiety symptoms or disorders. RESULTS: No randomized controlled
      trials have been conducted in patients with bipolar disorder and any co-occurring
      anxiety disorder. Among agents with antimanic or mood-stabilizing effects,
      evidence of efficacy from placebo-controlled trials exists for valproate in the
      treatment of panic disorder; lamotrigine, risperidone, and olanzapine in
      posttraumatic stress disorder; and risperidone, olanzapine, and quetiapine as
      adjunctive treatment in selective serotonin reuptake inhibitor-refractory
      obsessive-compulsive disorder. Antidepressants from virtually every class have
      efficacy in the treatment of most anxiety disorders but present the challenge of
      minimizing switch risk when used in conjunction with a moodstabilizer. Among
      novel antiepileptic agents without proven thymoleptic properties studied in
      randomized controlled trials in anxiety disorders, gabapentin and pregabalin had
      efficacy in the treatment of social anxiety disorder, and pregabalin in the
      treatment of generalized anxiety disorder. CONCLUSION: In the absence of
      controlled trials in patients with comorbid bipolar and anxiety disorders, the
      initial goals of treatment include mood stabilization and selection of
      thymoleptic agents with efficacy in the co-occurring anxiety disorder.

PMID- 16426112
TI  - Bipolar disorder and comorbid anxiety disorders in children and adolescents.
AB  - Recent attention has focused on the association between bipolar disorder and
      comorbid anxiety disorders in children and adolescents. There is a high rate of
      comorbidity between bipolar disorder and anxiety disorders in children and
      youths. Often, a child or adolescent with bipolar disorder has multiple comorbid
      anxiety disorders. In general, anxiety disorders precede the development of
      bipolar disorder in children. Comorbid disorders may worsen the course of each
      individual disorder. Pharmacologic management of the comorbid anxiety disorder is
      complicated by potential mood destabilization in a child or adolescent with
      bipolar disorder.

PMID- 16426113
TI  - Diagnosis and management of bipolar disorder with comorbid anxiety in the
      elderly.
AB  - Currently, in individuals over 65 year of age, prevalence rates of bipolar
      disorder range from 0.1% to 0.4%. As is the case for bipolar disorder in younger
      individuals, bipolar disorder may be unrecognized or underrecognized among older
      adults. While anxiety disorders are frequently comorbid among younger individuals
      with bipolar illness, the prevalence and impact of comorbid anxiety is far less
      understood among geriatric individuals with bipolar disorder, in whom anxiety
      disorders may be underreported. This comorbidity may have serious consequences,
      since in older adult populations with depression, the presence of comorbid
      anxiety is associated with more severe depressive symptoms, more chronic medical
      illness, greater functional impairment, and lower quality of life; the same
      associations may prove to be true in older patients with bipolar disorder. As
      with younger individuals with bipolar disorder, effective treatment of the
      underlying mood disorder is critically important before treating comorbid
      symptoms. Unfortunately, few evidence-based studies are available to guide the
      treating clinician in the management of these vulnerable patients, many of whom
      have additional psychiatric or medical comorbidity.

PMID- 16426114
TI  - Different standards.

PMID- 16426115
TI  - Child coping strategies, dental anxiety and dental treatment: the influence of
      age, gender and childhood caries prevalence.
AB  - AIM: This was to investigate what coping strategies are used by children, the
      efficacy of these strategies and the influences of age, gender, dental anxiety,
      pain experience and childhood caries prevalence (place of residence) upon the
      efficacy of the coping strategies used by Dutch (NL) children in The Netherlands
      and Northern Ireland (NI). METHODS: Convenience samples of Dutch and NI children
      were taken and asked to fill out a coping questionnaire (Dental Cope
      Questionnaire) and an anxiety schedule (CFSS-DS). Data were entered onto a SPSS
      database and subjected to frequency distributions, Chi-square analysis, t-tests
      and analysis of variance. RESULTS: The children used a wide variety of coping
      strategies in dealing with pain in dentistry. The most frequently used and those
      reported to have the greatest efficacy by the children in this investigation were
      cognitively based strategies. Different strategies were used in relation to place
      of residence, age and level of dental anxiety. The variance in the number of
      strategies used was significantly explained by the experienced pain during dental
      treatment. The efficacy of the coping strategies used was significantly explained
      by level of dental anxiety. CONCLUSIONS: Dental coping strategies used by
      children seem to vary with age, dental anxiety and pain experience. This
      information can help dental practitioners to adjust his or her treatment to the
      child's emotional needs.

PMID- 16426116
TI  - Treatment management of first permanent molars in children with Molar-Incisor
      Hypomineralisation.
AB  - AIM: To study the treatment management of first permanent molars in children with
      Molar-Incisor Hypomineralisation (MIH). STUDY DESIGN: Retrospective analysis.
      METHODS: The records of the clientele of a private paediatric dental practice
      were scanned. Thirty-six cases of children fulfilling the diagnostic criteria of
      MIH were retrieved who had been followed for a mean period of 4.5 years, and 36
      children of matching age and gender, and with similar follow-up period, were
      randomly selected from the same clientele to serve as controls. RESULTS: Children
      in the MIH group exhibited greater DMFS and smaller dmfs scores. The frequency of
      restorative intervention was greater in children of the MIH group (OREST=11.00,
      95% C.I. 2.85-42.45). Stainless-steel crowns had been placed only on MIH group
      molars. The follow-up records revealed that only restorations in the MIH group
      needed retreatment. Fillings and sealants in the MIH group had a greater
      probability of needing retreatment than in the control group (OREST=3.10, 95%
      C.I. 1.60-6.01). CONCLUSIONS: Children affected by MIH may need to undergo a
      significant amount of restorative treatment at an early age. Moreover, fillings
      and sealants in MIH affected children have a greater probability of needing
      retreatment than in control group children.

PMID- 16426117
TI  - Sealing ability and bond strength of four contemporary adhesives to enamel and to
      dentine.
AB  - AIM: To compare the shear bond strength and microleakage of four adhesive systems
      to the enamel and dentine of primary bovine teeth. METHODS: 120 bovine primary
      mandibular incisors were collected and stored in an aqueous 1% chloramine
      solution at room temperature for no longer than 3 months after extraction (80 for
      shear bond testing and 40 for microleakage evaluation). The adhesives tested were
      Clearfil SE bond (SE), Adper Prompt L Pop (LP), Xeno III (XE), and Prime and Bond
      NT (PB). For shear bond strength testing the specimens were wet ground to 600
      grit SiC paper to expose a flat enamel or dentine surface. After bonding and
      restoration with Dyract AP (DAP), the teeth were subjected to shear stress using
      a universal testing machine. For microleakage evaluation, facial class V cavities
      were prepared half in enamel and half in cementum. All cavities were restored
      with DAP. After thermocycling and immersion in 2% methylene blue, the dye
      penetration was evaluated under a stereomicroscope. STATISTICS: All data were
      analysed by Chi-square tests or Fisher's tests when adapted in order to determine
      the significant differences between groups. Results were considered as
      significant for p < 0.05. Results were analysed with an ANOVA test and a
      Bonferroni's multiple comparison. The level of significance was p < 0.05.
      RESULTS: Shear bond strength values (MPa,) ranged from: on enamel 11.06 to 5.34,
      in decreasing order SE, LP, XE and PB and on dentine 10.47 to 4.74, in decreasing
      order SE, XE, LP and PB. Differences in bond strengths between the four systems
      on enamel and dentine were all statistically significant, excepted for XE vs LP
      (shear bond at dentine). No significant differences were recorded in the
      microleakage degree between the four adhesive systems on enamel and on dentine (p
      > 0.0.5). CONCLUSIONS: The highest shear bond strength was achieved by Clearfil
      SE bond and the lowest by Prime and Bond NT. There was no significant difference
      concerning the sealing ability of the four adhesive systems.

PMID- 16426118
TI  - Laboratory comparison of a titanium trauma splint with three conventional ones
      for the treatment of dental trauma.
AB  - AIM: This was to evaluate the efficacy of a Titanium Trauma Splint (TTS) by
      comparing it with three other devices commonly used in the care of dental trauma,
      a Resin Splint (RS), Button-Bracket Splint (BS) and a Wire- Composite Splint
      (WCS). METHODS: The four types of splints were applied on experimental dental
      models, including in the splints the teeth from canine to canine of each maxilla.
      Two load-tests for each device were applied with the dental model inclined to 45
      degrees or less, and increasing forces were applied to the incisal edges from 0N
      to 50N, in the first test, and from 0N to 100N in the second. At the same time
      the displacement involved of the splinted teeth was assessed and then the ratio
      between the two measured sizes was graphically represented. RESULTS: In the level
      tests the displacements of the splinted teeth caused by the force of 80N were:
      0.39 mm for the BS, 0.37 mm for the TTS, 0.35 mm for the WCS and 0.30 mm for the
      RS. In the inclined tests, the splints under the effect of 40N, showed
      displacements as: 1.65 mm RS, 1.83 mm BS, 1.89 mm TTS and 2.16 mm WCS.
      CONCLUSION: With the exception of RS as to rigidity, the other three splints were
      practically the same in response. Considering other characteristics, the TTS
      proved to be a promising device for the treatment of dental traumas.

PMID- 16426119
TI  - Sweetened medicines and hospitalization: caries risk factors in children with and
      without special needs.
AB  - AIM: This was to evaluate caries risk factors: medicine consumption level, oral
      hygiene frequency and oral hygiene habits during hospitalization of children with
      and without special needs. METHODS: A cross-sectional study was carried out using
      a pre-tested form, interviews were conducted with guardians of children with (G1
      116) and without special needs (G2-86), from a public day nursery in Rio de
      Janeiro (Brazil). RESULTS: Average use of medications was at 21.8 months for G1-
      24.5 and G2--7.2 (Mann-Whitney: p-value = 0.0009). In the total sample, medicines
      were taken usually at night; 8.4% of parents sweetened them before ingestion and
      the majority of children did not brush their teeth after taking medicines. More
      than half (61.9%) had been hospitalized with an average duration of 21.8 days; 83
      (66.4%) had had few hospitalizations; G1--62.8% and G2--77.4%. Some 81.6% of the
      sample reported no tooth brushing while in hospital. STATISTICS: The data were
      entered in the EPI INFO 6.04d program, and the tests used were Fisher Exact, Mann
      Whitney, Kruskal-Wallis and Chi-square with a 5% significance level. CONCLUSIONS:
      Poor oral hygiene habits when taking medicines and during hospitalizations were
      observed, mainly among children with special needs.

PMID- 16426120
TI  - The dental attitudes, knowledge and health practices of patients with Juvenile
      Idiopathic Arthritis.
AB  - AIM: To investigate the dental attitudes, knowledge and dental health practices
      of children and adults with a previous diagnosis of Juvenile Idiopathic Arthritis
      (JIA). STUDY DESIGN: A self-completion questionnaire. METHODS: Ninety-one
      children and 82 adults with JIA were age and gender matched with 152 healthy
      controls. For those below the age of 16 years, the parents' attitude, knowledge
      and dental health practices were investigated by the questionnaire. The adult
      subjects and controls completed an identical questionnaire assessing their own
      attitude, knowledge and dental health practices. RESULTS: Response rates of 84%
      and 75% were achieved for the subject and controls respectively. Both groups
      responded similarly to questions assessing perception of different medical
      conditions. The majority of respondents thought leukaemia was a very serious
      condition. Twenty-seven percent of subjects and 34% of controls felt dental decay
      was "slightly or not serious". Ninety percent of subjects and 93% of controls
      knew having sweet snacks during the day would harm teeth, but fewer were sure
      that eating sweet foods at mealtimes only would help reduce decay. The majority
      of respondents (63% and 56% respectively) did not know whether children should
      receive fluoride tablets but the majority of subjects in both groups had attended
      a dentist within the last year. STATISTICS: Descriptive analyses and chi-squared
      analysis were undertaken. A p-value of < or =0.01 was taken as strong evidence of
      a difference between groups. CONCLUSION: The perception of health and illness by
      both groups was appropriate. The questions investigating dental knowledge
      revealed understanding of the basic messages of prevention of dental disease, but
      finer detail appeared less well understood. Responses concerning dental health
      confirmed positive attitudes towards good dental health habits. The benefits of
      brushing with fluoride toothpaste were known, and the majority toothbrushed daily
      and received dental care within the previous year.

PMID- 16426122
TI  - Single-center experience using three shockwave lithotripters with different
      generator designs in management of urinary calculi.
AB  - PURPOSE: We retrospectively reviewed the treatment outcomes of extracorporeal
      shockwave lithotripsy (SWL) in a single center using either the Wolf Piezolith
      2300 (a piezoelectric lithotripter), the Dornier MPL9000 (an electrohydraulic
      lithotripter), or the Dornier Compact Delta (an electromagnetic lithotripter)
      from January 1992 to June 2002. PATIENTS AND METHODS: A series of 3123 (1449
      Piezolith 2300, 780 MPL9000, and 894 Compact Delta) solitary radiopaque urinary
      stones of < or =15 mm receiving primary SWL were identified. "Stone free" was
      defined as the absence of evidence of stone on plain radiography. Treatment
      outcomes were assessed by the stone-free rate 3 months after one treatment
      session, the retreatment rate, the auxiliary procedure rate, the complication
      rate, and the effectiveness quotient (EQ). In order to have a better assessment
      of the efficacy of individual lithotripters, multiple logistic regression was
      performed to control various factors affecting treatment outcomes, including
      lithotripter-type, patients' sex and age, history of previous SWL, the stone
      characteristics (side, site, and size), and the presence of a stent or
      nephrostomy tube. RESULTS: There were significant differences in the stone site
      distribution and mean stone size among the three groups. The overall EQ for the
      Piezolith 2300, MPL9000, and Compact Delta were 0.345, 0.303, and 0.257,
      respectively. However, using the multiple logistic regression model, the adjusted
      odds ratio (AOR) of a patient being stone-free after 3 month for the Piezolith
      2300 and MPL9000 (using the Compact Delta as the referent category) were 1.38
      (95% CI 1.15, 1.65) and 1.72 (95% CI 1.39, 2.11), respectively. Patients treated
      using the MPL9000 had significantly less re-treatment (AOR = 0.57; 95% CI 0.48,
      0.69) than the other groups. No significant difference in the auxiliary procedure
      rate and complication rate for the three machines was observed. CONCLUSION: Based
      on multivariate analysis results, the Dornier MPL9000 had the best treatment
      outcomes in terms of stone-free rate and re-treatment rate among the three
      lithotripters.

PMID- 16426121
TI  - Prevalence of enamel defects and MIH in non-fluoridated and fluoridated
      communities.
AB  - AIM: This was to study the prevalence of enamel defects and molar incisor
      hypomineralisation (MIH) in children attending Leeds Dental Institute (UK) and
      Westmead Dental Hospital, Sydney (Australia). METHODS: Prospective dental
      examinations were carried out on 25 children referred to two orthodontic
      departments. A questionnaire was completed to obtain background information and
      about previous fluoride (F) exposure followed by an oral examination. First
      permanent molars and permanent incisors were examined for presence, type and
      severity of enamel defects using the modified DDE screening index. Chi square
      tests were used to compare results. RESULTS: Data for 24 children in Sydney and
      20 in Leeds presented with at least one enamel defect. Of 300 teeth examined, 155
      in Sydney and 82 in Leeds had a defect (p < 0.005). Severity of enamel defects
      was higher in Sydney. The children presenting with any type of enamel defect in
      at least one incisor or molar were 21 in Sydney and 10 in Leeds. However, if only
      demarcated defects were considered, the number in Sydney dropped to 11 and in
      Leeds remained at 10. CONCLUSIONS: There was a higher prevalence of enamel
      defects in those children living in F Sydney than in non-F Leeds, but the
      prevalence of MIH was the same supporting the view that F is not associated with
      the aetiology of MIH.

PMID- 16426123
TI  - Initial experience with a prototype ureteroscope.
AB  - BACKGROUND AND PURPOSE: We report our initial experience with a prototype
      ureteroscope having the smallest tip diameter and shaft with an offset eyepiece
      for the treatment of ureteral stones. PATIENTS AND METHODS: A series of 21 male
      and 4 female patients between the ages of 1.5 and 57 years underwent treatment
      with the new ureteroscope for stones in the lower (24) and middle (1) ureter. All
      four of the children were boys. All patients were operated on by a single
      urologist. Patient sex, age, side, location and size of stone, type of
      anesthesia, requirement for a guidewire, use of stent, requirement for ureteral
      dilatation, operative time, type of intracorporeal lithotripsy used if any, type
      of stone-grasping device used, success rate, length of hospital stay, and
      complications were recorded. RESULTS: None of the patients required ureteral
      dilatation, and a guidewire was used in only three patients. Eight patients were
      operated on with instillation of 2% lidocaine gel alone, while another five
      patients required intravenous pentazocine and midazolam. Eight patients were
      operated on with monitored anesthesia care under propofol and one under ketamine.
      Three patients required general anesthesia. A double-J stent was not required in
      15 patients. The success rate was 100%, and complications were minor. CONCLUSION:
      The new ureteroscope can treat the majority of lower-ureteral stones of up to 1.2
      cm even in male patients under lidocaine gel with or without intravenous sedation
      or monitored anesthesia care. These patients can be treated as day-care cases.
      None of the patients required ureteral dilatation, and stent is now being omitted
      in most patients. All children were treated in one session.

PMID- 16426124
TI  - Medical expulsive treatment of distal-ureteral stones using tamsulosin: a single
      center experience.
AB  - PURPOSE: To evaluate the efficacy of the addition of tamsulosin to our standard
      expulsive pharmacologic therapy for the treatment of distal-ureteral stones.
      PATIENTS AND METHODS: A series of 96 patients referred to our department for the
      management of symptomatic distal-ureteral calculi were randomly divided into
      group 1 (N = 46) who received diclofenac (100 mg/daily) plus aescin (80 mg/daily)
      and group 2 (N = 50) who received the same therapy plus tamsulosin (0.4 mg/daily)
      for a maximum of 2 weeks. There were no differences between the groups with
      respect to age, sex, or stone size. The primary endpoint was the expulsion rate.
      Expulsion time, need for analgesics, need for hospitalization, and drug side
      effects were the secondary endpoints. RESULTS: The expulsion rate was
      significantly higher in group 2 (90%) than in group 1 (58.7%; P = 0.01), and
      group 2 achieved stone passage in a shorter time (mean 4.4 v 7.5 days,
      respectively; P = 0.005). Lower analgesic use was found in group 2 (P = 0.003),
      as well as significantly fewer hospitalizations for recurrent colic (P = 0.01).
      Both groups experienced few side effects associated with expulsive therapy.
      CONCLUSIONS: A conservative approach should be considered as an option in the
      management of uncomplicated distal-ureteral stones. Even if the best
      pharmacologic expulsive regimen remains to be established, the use of the
      selective alpha-blocker tamsulosin is recommended in this setting.

PMID- 16426126
TI  - Case report: simultaneous laparoscopic management of bilateral ureteropelvic
      junction obstruction in a horseshoe kidney.
AB  - A 42-year-old man presented with a horseshoe kidney with a nonfunctioning left
      moiety and bilateral ureteropelvic junction obstruction. Concomitant laparoscopic
      left nephrectomy and right pyeloplasty was performed. The total operative time
      was 5.7 hours, with a blood loss of <350 mL. There were no complications, and the
      hospital stay was 3 days. This appears to be the first such case reported.

PMID- 16426125
TI  - Previous open nephrolithotomy: does it affect percutaneous nephrolithotomy
      techniques and outcome?
AB  - BACKGROUND AND PURPOSE: The consequences of open nephrolithotomy are scar tissue
      around the kidney and in the retroperitoneum and distortion of the pelvicaliceal
      anatomy that may affect the techniques and outcome of percutaneous
      nephrolithotomy (PCNL). We compared the results and complications of patients
      undergoing PCNL who had and had not previously undergone open nephrolithotomy.
      PATIENTS AND METHODS: A total of 178 calculi in 175 patients who had previously
      had open nephrolithotomy (group I) and 178 calculi in 175 patients who had never
      had a renal operation (group II) were treated with PCNL. The average time between
      open nephrolithotomy and PCNL was 8.5 years (range 4 months-22 years). In both
      groups, PCNL was done by a standard technique with serial Amplatz dilator
      enlargement of the tract to 30F. Upper-pole access under fluoroscopic guidance
      was done in most patients. The operative time, success rate, hospital stay, and
      complications in the two groups were compared. RESULTS: The stone-free rates were
      80.3% and 82.6% in groups I and II, respectively, and the rate of residual
      fragments < or =4 mm was 14.6% and 8.4%. The operative time, success rate,
      hospital stay, and complications did not differ significantly in the two groups.
      CONCLUSION: Percutaneous nephrolithotomy is effective and safe in patients who
      have previously had open nephrolithotomy with no more complications than are seen
      with PCNL of kidneys that have not been operated on.

PMID- 16426127
TI  - Case report: laparoscopic partial nephrectomy for isolated renal hydatid disease.
AB  - A 73-year-old male patient with an isolated calcified hydatid cyst in the lower
      pole of the right kidney presented with a history of weight loss and cloudy, foul
      smelling urine. Laparoscopic partial nephrectomy was performed, at which the cyst
      was removed en bloc. Six months postoperatively, a CT scan revealed no recurrence
      of hydatidosis. To our knowledge, this is the first report of laparoscopic
      partial nephrectomy for the treatment of isolated renal echinococcosis.

PMID- 16426128
TI  - Delayed presentation of urinoma after radiofrequency ablation-assisted
      laparoscopic partial nephrectomy.
AB  - PURPOSE: To examine the outcomes and complications of thermal ablation-assisted
      laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Radiofrequency
      ablation (RFA)-assisted laparoscopic partial nephrectomy was employed in 16
      consecutive renal masses with a mean size of 3.0 cm over 12 months. The
      indications were primarily adjacent bowel, hilar location, or both. After RFA,
      the renal mass was laparoscopically excised and examined pathologically. RESULTS:
      The mean operative treatment time was 99 minutes. The estimated blood loss was
      121 mL, and no patient required a blood transfusion. Urinoma was diagnosed in
      three patients at an average of 13 days postoperatively and resolved with
      conservative management or ureteral stent placement. CONCLUSIONS: Radiofrequency
      ablation-assisted LPN provides effective hemostasis and, in the short term,
      cancer control. In this setting, urinoma presents as ipsilateral flank pain 1 to
      2 weeks after surgery. The proposed mechanism for the delayed presentation is
      thermal injury to the collecting system, although an unrecognized direct
      collecting-system injury is possible. Conservative management, ureteral stent
      placement, or both led to resolution of all of the urinomas.

PMID- 16426129
TI  - Case report: robot-assisted laparoscopic pyeloureterostomy in a transplanted
      kidney with ureteral stricture.
AB  - Ureteral obstruction secondary to ischemia is the most common urologic
      complication of kidney transplantation. Although endoscopic management has shown
      satisfactory short-term success rates, surgical repair is considered the
      definitive therapy. To our knowledge, this procedure has been performed only
      through open surgery. We present a minimally invasive approach for reconstruction
      of a ureteral stricture in a renal transplant patient using the Da Vinci robotic
      system.

PMID- 16426130
TI  - Self-retaining ureteral stents: analysis of factors responsible for patients'
      discomfort.
AB  - PURPOSE: To determine factors affecting patients' discomfort during the period
      self-retaining ureteral stents are in place. PATIENTS AND METHODS: Between April
      2001 and May 2003, 58 male and 42 female patients underwent temporary double
      pigtail stenting. The indications were endopyelotomy in 39 patients, ureteroscopy
      in 32, laparoscopic pyeloplasty in 18, and endoureterotomy in 11. The stents were
      silicone in 56 patients and Percuflex in 44. The median stenting period was 8
      weeks (range 4-16 weeks). Patient discomfort was evaluated by a questionnaire
      conducted by the physician before stent removal. Tested variables were patients'
      sex, side of the stent, urine culture, stent material, stent length and diameter,
      and stenting duration. The site of the upper coil (renal pelvis or calix), the
      site of the lower coil (in the same side or crossing the midline), and the shape
      of the lower coil (complete circle or not) were also tested. Univariate and
      multivariate analysis were carried out to determine significant independent
      variables, with P < 0.05 being significant. RESULTS: Of the total, 59 patients
      experienced discomfort consisting of dysuria, urgency, urge incontinence, loin
      pain, suprapubic pain, frequency, nocturia, or gross hematuria or some
      combination. Significant factors associated with discomfort were a positive urine
      culture, crossing of the lower end of the stent to the opposite side, caliceal
      position of the upper coil, and longer stenting duration. CONCLUSION: Proper
      positioning of the coils of the stent, eradication of infection, and shorter
      stenting duration are advised to decrease patient discomfort during the period of
      ureteral stenting.

PMID- 16426131
TI  - Low-power holmium:YAG laser urethrotomy for treatment of urethral strictures:
      functional outcome and quality of life.
AB  - PURPOSE: To evaluate the efficacy of endourethrotomy with the holmium:YAG laser
      as a minimally invasive treatment for urethral stricture. PATIENTS AND METHODS:
      Between January 2002 and January 2004, 32 male patients with symptomatic urethral
      strictures (8 bulbar, 9 penile, 9 combined) were treated with Ho:YAG-laser
      urethrotomy in our department. The stricture was iatrogenic in 60% (N = 18),
      inflammatory in 16.6% (N = 5), traumatic in 13.3% (N = 4), and idiopathic in 7%
      (N = 3). The stricture was incised under vision at the 12 o'clock location or the
      site of maximum scar tissue or narrowing in asymmetric strictures. Laser energy
      was set on 1200 to 1400 mJ with a frequency of 10 to 13 Hz. Postoperatively,
      drainage of the bladder was performed for 4 days using a 18F silicone catheter.
      Triamcinolone was instilled intraurethrally after removal of the catheter in all
      patients. Patients were followed up by mailed questionnaire, including
      International Prostate Symptom Score and quality of life. RESULTS: Retrograde
      endoscopic Ho:YAG laser urethrotomy could be performed in all 32 patients. Most
      patients (22; 68.7%) did not need any reintervention. Ten patients developed
      recurrent strictures that were treated by another laser urethrotomy in 4 patients
      (12.5%), while 6 patients (18.7%) needed open urethroplasty with buccal mucosa.
      Including 2 patients treated with repeat laser urethrotomy, 24 patients (75%)
      were considered successful after a mean follow-up of 27 months (range 13-38
      months). No intraoperative complications were encountered, although in 5% of
      patients, a urinary-tract infection was diagnosed postoperatively. No gross
      hematuria occurred. CONCLUSIONS: The Ho:YAG laser urethrotomy is a safe and
      effective minimally invasive therapeutic modality for urethral stricture with
      results comparable to those of conventional urethrotomy. Further data from long
      time follow-up are necessary to compare the success rate with that of
      conventional urethrotomy and urethroplasty. Nevertheless, the Ho:YAG laser
      urethrotomy might at least be an alternative to urethroplasty in patients with
      high comorbidity who are not suitable for open reconstruction.

PMID- 16426132
TI  - Case report: endoscopic treatment of isolated congenital urethroperineal fistula.
AB  - Isolated congenital urethrocutaneous fistula is an extremely rare congenital
      anomaly. Management is sometimes complex and depends on the location. We report
      our endoscopic treatment in a man with a urethroperineal fistula.

PMID- 16426133
TI  - Laparoscopic radical prostatectomy using an extraperitoneal approach: Nordwest
      hospital technique and initial experience in 255 cases.
AB  - PURPOSE: We report on our modifications in technique and initial experience with
      255 extraperitoneal laparoscopic radical prostatectomy (eLRP). PATIENTS AND
      METHODS: Using significant surgical modifications, our laparoscopic method
      replicates the steps of the retropubic descending RP. We evaluated 255
      consecutive patients who underwent an eLRP with pelvic lymph-node dissection.
      RESULTS: The mean operative time was 136 minutes (range 84-266 minutes). Because
      of technical difficulty, the first three patients were converted to open surgery.
      One major complication, myocardial infarction, and one surgical reintervention in
      a case of secondary rectourethral fistula after open surgical repair of a
      laparoscopic rectal injury were observed. The blood transfusion rate was 1.2%.
      The pathologic stage was pT2a in 56 patients (22%), pT2b in 50 (20%), pT2c in 74
      (29%), pT3a in 42 (16%), pT3b in 29 (11%), and pT4 in 3 (2%). Positive margins
      were found in 7% of patients (13/180) with pT2 tumors and 27% of patients (19/71)
      with pT3 tumors. The mean catheterization time was 7 days. The continence rates
      (no pads at all) at 3, 6, and 12 months were 73.7% (146/198), 89.6% (112/125),
      and 92.7% (38/41), respectively. After a nerve-sparing procedure, the total
      potency rates at 3 and 6 months were 37.5% (21/56) and 48.8% (21/43),
      respectively. CONCLUSION: The eLRP seems to be safe with short-term oncologic and
      functional results at least as favorable as those of open radical prostatectomy
      and classical transperitoneal LRP. The operative times are shorter, and the
      complication rate appears to be lower.

PMID- 16426134
TI  - Comparison of resolution, contrast, and color differentiation among fiberoptic
      and digital flexible cystoscopes.
AB  - BACKGROUND AND PURPOSE: Advances in electro-optics continue to improve the
      urologist's ability to perform minimally invasive procedures. While the
      development of flexible fiberoptic cystoscopes more than 20 years ago greatly
      impacted the practice of urology, distal-sensor digital technology may represent
      the next step in the evolution of endoscopy. We compared a new distal-sensor
      digital flexible cystoscope with two standard fiberoptic flexible cystoscopes.
      MATERIALS AND METHODS: We evaluated the resolution, contrast, and color
      discrimination of a new ACMIICN distal-sensor digital cystoscope with >165,000
      effective pixels in its clear aperture (viewing area), a new ACMI-ACN II
      fiberoptic cystoscope with <15,000 pixels in its clear aperture, and a Storz 1127
      office fiberoptic cystoscope. Five subjects compared each cystoscope across 13
      test parameters. RESULTS: There was no difference in the performance of the two
      fiberoptic cystoscopes. The ICN cystoscope was statistically superior to one or
      both fiberoptic cystoscopes across 12 of the 13 tests, including color
      differentiation between shades of dark red (P < 0.05), contrast discrimination
      along a 15-step grayscale gradient (P < 0.001 compared with the 1127 fiberoptic
      cystoscope only), resolution at 10 mm (7.52 line pairs/mm [lp/mm] (ICN) nu 3.58
      lp/mm for both fiberoptic cystoscopes; (P < 0.001), and clear resolution of a 1
      mm target at a distance of 6.1 cm (ICN) nu 3.3 cm (1127) and 3.8 cm (ACN II) (P <
      0.001). CONCLUSIONS: The ICM distal-sensor all-digital cystoscope was clearly
      superior to two representative fiberoptic cystoscopes in vitro in terms of
      resolution, contrast discrimination, and red color differentiation. In-vivo
      performance remains to be assessed.

PMID- 16426135
TI  - Vickers hardness studies of calcium oxalate monohydrate and brushite urinary
      stones.
AB  - PURPOSE: To measure the hardness of two types of urinary stones: calcium oxalate
      monohydrate (COM; CaC2O4 . H2O) and dicalcium phosphate dihydrate (brushite;
      CaHPO4 . 2H2O). MATERIALS AND METHODS: The composition of 28 calcium oxalate
      monohydrate and 22 brushite stones was characterized by infrared spectroscopy (FT
      IR). Stone specimens were embedded in crystallographic resin, polished, and
      subjected to indentation tests using a Vickers tester. The hardness was
      calculated from measuring the diagonal lengths of the residual indentation on the
      specimen using the appropriate equation. RESULTS: The COM stones showed hardness
      values ranging from 15.3 to 64.2 HV with a mean of 35.8 +/- 13.3, while brushite
      stones ranged from 10.1 to 46.1 HV with a mean of 26.5 +/- 15.1. The results of
      ANOVA showed that there were significant differences (P < 0.05) between the two
      stone types. CONCLUSIONS: Calcium oxalate monohydrate stones exhibited greater
      hardness than brushite stones when assessed with Vickers studies.

PMID- 16426137
TI  - Construct validity of the chicken model in the simulation of laparoscopic radical
      prostatectomy suture.
AB  - BACKGROUND AND PURPOSE: For a simulation to be valid, it has to be close to
      reality, correlate with the performance in a real case, and be able to
      discriminate between individuals with different degrees of experience. We
      explored the construct validity (ability to discriminate between experienced and
      inexperienced subjects) of a simulation for the urethrovesical anastomosis during
      laparoscopic radical prostatectomy (LRP). MATERIALS AND METHODS: Dead chickens
      were used. After partial emptying of the corporal cavity, an 18F catheter was
      placed through the esophagus to the stomach. In the Pelvic Trainer, a
      laparoscopic section of the esophago-glandular-stomach junction and a suture
      between the two edges were performed in the same fashion as for a urethrovesical
      suture in LRP. Five subjects with different levels of experience in laparoscopy,
      ranging from nil to more than 250 LRPs, tested two types of suture. One-way ANOVA
      was used to detect differences in suturing time among the operators. A multiple
      comparison test was used to detect specific differences between operators.
      RESULTS: Although suturing time had a strong negative correlation with the
      operator's experience, significant statistical differences in suturing time were
      found only between the least experienced operator and the other ones. Qualitative
      differences in the suture were found among operators. CONCLUSION: This simulation
      correlates well with the laparoscopic (LRP) subject's experience. It can
      discriminate between inexperienced and experienced subjects, exhibiting moderate
      construct validity, but failed to reflect the different levels of experience
      among the most experienced subjects.

PMID- 16426136
TI  - Aging assessment by dynamic mechanical analysis of in vivo encrusted polymeric
      urinary stents.
AB  - PURPOSE: To investigate the viscoelastic properties of plastic pigtail stents
      after removal from patients using the method of dynamic mechanical analysis
      (DMA). MATERIALS AND METHODS: Dynamic mechanical analysis was performed in 12
      polymeric pigtail stents left indwelling for various periods of time (0-120
      days). The encrustations were characterized by infrared spectroscopy, and their
      morphology was observed using scanning electron microscopy. RESULTS: Softening
      and stiffening behavior was observed. Stiffening was found specifically in the
      stents with heavy mineral deposits. CONCLUSIONS: Material degradation becomes
      obvious after certain periods of time. The effect of stent degradation appeared
      in two forms: softening of the stent polymer, possibly through interaction with
      urine, and stiffening of the stent secondary to the formation of various
      insoluble mineral deposits covered by layers of organic matrix.

PMID- 16426139
TI  - Comparison of nonabsorbable polymer ligating and standard titanium clips with and
      without a vascular cuff.

PMID- 16426138
TI  - Alteration in irrigant flow and deflection of flexible ureteroscopes with nitinol
      baskets.
AB  - BACKGROUND AND PURPOSE: Introduction of an instrument into the working channel of
      ureteroscopes adversely affects flow and deflection. We evaluated the alterations
      in ureteroscope channel flow and deflection caused by available Nitinol(R)
      baskets. MATERIALS AND METHODS: We compared the effects of 11 Nitinol baskets on
      irrigation flow and deflection of three flexible ureteroscopes (Olympus P3, ACMI
      DUR8, and ACMI DUR8 Elite). ANOVA was used to compare the loss of flow and
      deflection for each basket, with P values adjusted for multiple comparisons by
      the Tukey method. RESULTS: Ureteroscope flow and deflection were progressively
      adversely affected by all baskets as their diameter increased. The average
      baseline irrigant flow (46.6 mL/min) was decreased significantly: by 78.5% (to
      9.9 mL/min), with the smaller baskets (Microvasive 1.9F and Cook 2.2F) and by
      99.1% (to 0.4 mL/min) with the larger baskets (ACMI 3.0F and Microvasive 3.0F).
      Similarly, the mean baseline upward deflection (162 degrees) decreased by 2
      degrees (1.2%) for the Cook 2.4F N-Compass and by 20 degrees (12.3%) for the ACMI
      3.0F. Loss of downward deflection from baseline (170 degrees) ranged from 6
      degrees (3.5%) for the Microvasive 1.9F to 17 degrees (10%) for the Microvasive
      2.6F grasping forceps. The least deterioration in flow and deflection occurred
      with the two smallest baskets (Microvasive 1.9F and Cook 2.2F). CONCLUSION:
      Ureteroscope irrigation flow and deflection deteriorate progressively with larger
      caliber Nitinol baskets. The Microvasive 1.9F and Cook 2.2F baskets resulted in
      the least deterioration of irrigation and deflection metrics. However, basket
      size is not the only factor responsible for changes in flow and ureteroscope
      deflection.

PMID- 16426142
TI  - Induction of interferon synthesis by the PKR-inhibitory VA RNAs of adenoviruses.
AB  - In virus-infected cells, double-stranded RNA (dsRNA) activates the transcription
      factor interferon (IFN) regulatory factor-3 (IRF-3), which stimulates type I IFN
      (IFN-alpha/beta) gene expression. In addition, dsRNA activates the enzyme RNA
      activated protein kinase (PKR), which phosphorylates the eukaryotic initiation
      factor 2alpha (eIF2beta), thereby inhibiting mRNA translation. Adenoviruses
      express highly structured RNA molecules termed VA RNAs (VA(I)/VA(II)) known to
      specifically inhibit PKR. As PKR impairs expression from transfected cDNA
      constructs, plasmids encoding VA RNAs are widely used as enhancers of transgene
      expression. Here, we describe induction of IFN synthesis as a novel feature of VA
      RNAs. Transfection of a VA(I)/VA(II)-expressing plasmid was found to induce type
      I IFN production, resulting in activation of IFN-dependent genes, such as IFN
      stimulated gene 56 (ISG56) or MxA, and the establishment of an antiviral state in
      transfected cells. Curiously, VA RNAs did not activate IRF-3, suggesting an
      alternative pathway of IFN induction. These data may be considered when using
      genetically modified adenoviruses as therapeutic agents and suggest caution in
      choosing VA RNA constructs as a means to increase expression of a gene of
      interest.

PMID- 16426143
TI  - Efficacy and tolerability of pegylated IFN-alpha in patients with neuroendocrine
      gastroenteropancreatic carcinomas.
AB  - Interferon-alpha (IFN-alpha) is well established in the treatment of
      neuroendocrine carcinomas (NEC). Treatment is accompanied by fatigue and flu-like
      symptoms. In patients with chronic hepatitis C, pegylated IFN (PEGIFN) leads to
      improved antiviral efficacy and good tolerability. Our aim was to assess the
      efficacy and tolerability of PEG-IFN on the management of patients with well
      differentiated NEC of the gastroenteropancreatic system. In 17 patients, the
      effect of PEG-IFN-alpha2b was studied. After first-line octreotide treatment, IFN
      alpha was added at the time of tumor progression. Six patients were switched from
      conventional IFN-alpha, and 11 patients were IFN naive. Inhibition of tumor
      growth, including stabilization of disease, occurred in 13 of 17 patients, and
      biochemical and symptomatic responses were seen in 7 of 10 patients with
      functionally active tumors. Tolerability of PEG-IFN-alpha2b was much better than
      that of IFN-alpha. Fatigue occurred in 59% of all patients but was mild in
      severity. Eleven of thirteen patients who had a benefit remained on therapy for a
      median time of 20 months (range 6-30 months). PEG-IFN-alpha2b provides
      symptomatic and antiproliferative efficacy in patients with NEC. Better
      tolerability of PEG-IFN-alpha2b improved patients' compliance, justifying its use
      in patients who do not tolerate conventional IFN-alpha treatment.

PMID- 16426144
TI  - Stat1 expression is not sufficient to regulate the interferon signaling pathway
      in cellular immortalization.
AB  - DNA hypermethylation in gene promoters is an epigenetic mechanism regulating gene
      expression in cellular immortalization, an important step in carcinogenesis.
      Previously, we studied the genes dysregulated during immortalization using
      spontaneously immortalized fibroblasts from patients with Li-Fraumeni syndrome
      (LFS), who carry a germline mutation in the tumor suppressor gene p53. We found
      that multiple interferon (IFN) signaling pathway genes were regulated by
      epigenetic silencing. In this study we focused on a key regulator of that
      pathway, the signal transducer and transcription activator 1 (Stat1) gene.
      Although Stat1 is downregulated after cellular immortalization and upregulated in
      immortal MDAH041 cells after 5-aza-2'-deoxycytidine (5-aza-dC) treatment, we
      detected no methylation of the Stat1 promoter region in these cells before or
      after immortalization. To analyze the function of Stat1 in immortalization, we
      expressed Stat1 in immortal MDAH041 cells by stable infection, expecting to
      induce IFN-regulated genes or cellular senescence or both. However, the
      overexpression of Stat1 alone was not sufficient to repress the proliferation
      rate of immortal MDAH041 cells or induce senescence in immortal MDAH041 cells. We
      concluded that factor(s) additional to Stat1 (whether IFN dependent or not) are
      required for the immortalization of LFS fibroblasts.

PMID- 16426145
TI  - Mycobacterium tuberculosis H37Ra and H37Rv differential growth and
      cytokine/chemokine induction in murine macrophages in vitro.
AB  - The role of tumor necrosis factor-alpha (TNF-alpha) in controlling growth of
      Mycobacterium tuberculosis in murine peritoneal macrophages infected in vitro was
      studied. TNF-alpha was shown to be required but not sufficient, and the amount of
      TNF-alpha produced by the infected cells did not correlate with the extent of
      growth control. In this system, TNF-alpha-dependent control of growth of the
      avirulent strain H37Ra was independent of inducible nitric oxide synthase (iNOS)
      and interferon-gamma (IFN-gamma), as shown by the infection of macrophages from
      selected gene-disrupted mice. TNF-alpha-mediated bacteriostasis of H37Ra in the
      infected macrophages was associated with increased expression of selected Th1
      type cytokines and chemokines. In contrast, growth of the virulent strain H37Rv
      in macrophages involved upregulation by infected cells of Th2-type cytokines,
      including interleukin-5 (IL-5), IL-10, and IL-13. Taken together, these results
      suggest that the particular nature of macrophage activation and the cytokine and
      chemokine response to infection with different M. tuberculosis strains determine
      the ability of the cells to control the growth of the intracellular bacilli.

PMID- 16426146
TI  - The effects of dehydroepiandrosterone (DHEA) on in vitro spleen cell
      proliferation and cytokine production.
AB  - Dehydroepiandrosterone (DHEA), a weak androgenic steroid, has been associated
      with enhancing immune responses and upregulating resistance against viral,
      parasitic, and bacterial infections. The objective of this study was to assess
      the effects of DHEA on murine spleen cell viability, proliferation, and cytokine
      production following in vitro stimulation with the mitogens concanavalin A (ConA)
      and lipopolysaccharide (LPS). Results showed that exposure to 6 microM DHEA
      significantly decreased the viability and proliferation of murine spleen cells
      stimulated with LPS, whereas no effect was seen on murine spleen cells stimulated
      with ConA. DHEA did influence the production of both ConA-induced and LPS-induced
      cytokines. DHEA also significantly reduced the mitogen-induced production of the
      proinflammatory cytokine interleukin-1 (IL-1) as well as the Th1 cytokines IL-2
      and interferon-gamma (IFN-gamma). Increasing concentrations of DHEA significantly
      increased the production of the Th2 cytokine IL-10 but had no effect on the
      production of the Th2 cytokine IL-4, the proinflammatory cytokine tumor necrosis
      factor-alpha (TNF-alpha), or IL-6. These results suggest that DHEA may be an
      important factor for increasing Th2 cytokine production and decreasing Th1 and
      proinflammatory cytokine production. This study provides a more comprehensive
      understanding of the effects of DHEA on the rates of cell proliferation, cell
      viability, and cytokine production.

PMID- 16426147
TI  - Antiviral activity of transiently expressed IFN-kappa is cell-associated.
AB  - Most type I interferons (IFNs) are expressed by the majority of cell types in
      response to viral infection. In contrast, IFN-kappa has been reported to have a
      cellular distribution limited to keratinocytes and certain lymphoid cell
      populations. Recombinant expressed IFN-kappa has been shown previously to possess
      weak antiviral activity when directly compared with IFN-beta. In order to expand
      on the antiviral potential of IFN-kappa, we transiently transfected human cell
      lines to circumvent the need to purify recombinant proteins and to avoid the
      possible loss of biologic activity by the purification process. We evaluated the
      transcriptional signaling and antiviral activity of IFN-kappa in parallel with
      IFN-alpha2b with mammalian expression vectors to express each protein
      transiently. Both IFN-kappa and IFN-alpha2b exhibited comparable transcriptional
      and antiviral activities. However, in contrast to IFN-alpha2b transcriptional
      signaling and antiviral activity, IFN-kappa activity was not detectable in
      conditioned cell culture medium. Subsequent experiments revealed there was a
      direct relationship between IFN-kappa-expressing cells and antiviral activity.
      These results were confirmed in immunocytochemical studies. Furthermore, IFN
      kappa exhibited cell-associated antiviral activity against a hepatitis C virus
      (HCV) replicon cell line. This novel IFN signaling strategy may represent an
      important distinct and divergent mechanism for limiting viral infections.

PMID- 16426150
TI  - Dual infection with Mycobacterium tuberculosis and Pneumocystis jiroveci
      Lymphadenitis in a Patient with HIV infection: case report and review of the
      literature.
AB  - We report a case of dual Mycobacterium tuberculosis (TB) and Pneumocystis
      jiroveci (carinii) (PCP) lymphadenitis in a patient with HIV who had been
      receiving trimethoprim-sulfamethoxazole (TMP-SMX) as systemic prophylaxis for
      PCP. This patient was successfully treated with antituberculosis medications and
      TMP-SMX. Our review of the literature identified this as the first reported case
      of dual TB and PCP lymphadenitis in an HIV-infected host and highlights the
      potential limitations of TMP-SMX prophylaxis.

PMID- 16426148
TI  - Upregulation of IFN-gamma receptor expression by proinflammatory cytokines
      influences IDO activation in epithelial cells.
AB  - Interferon-gamma (IFN-gamma) induces the enzyme indoleamine dioxygenase (IDO) in
      a variety of human cell types. Furthermore, tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1 (IL-1) synergistically increase IFN-induced IDO
      activity. Inasmuch as cytokines can upregulate cytokine receptor expression, one
      mechanism of cytokine synergy may be at the level of receptor expression. To test
      the hypothesis that this mechanism of IDO regulation is active in epithelial
      cells, HeLa cells were treated with IFN-gamma, TNF-alpha, or IL-1beta to
      determine optimal cytokine concentrations and time for maximal cytokine receptor
      expression. Flow cytometric analysis with antibodies to receptors for IFN-gamma,
      TNF-alpha, or IL-1beta indicated that each cytokine upregulated expression of the
      other cytokine receptors by 4 h, with maximal expression observed between 16 and
      20 h after cytokine treatment. Furthermore, increases in IFN-gamma receptors
      (IFNGR) induced by IL-1beta were found to be dependent on NF-kappaB
      transactivation. To determine if increases in IFNGR expression alone contributes
      to synergistic IDO induction, cells were stimulated with IL-1beta to upregulate
      receptor expression, and the NF-kappaB concentration was allowed to return to
      basal levels. When treated with IFN-gamma, enhanced Stat1 signaling and IDO
      induction were still observed, indicating that increased cytokine receptor
      expression contributes to synergistic increases in IDO activity.

PMID- 16426151
TI  - Appearance-related side effects of HIV-1 treatment.
AB  - In the early years of the AIDS epidemic, HIV infection was associated with
      visible signs and symptoms, adding to the stigma associated with the disease.
      Physical manifestations associated with HIV infection included muscle wasting,
      lymphadenopathy, Kaposi's sarcoma, candidiasis, molluscum contagiosum, and hairy
      leukoplakia. With the advent of antiretroviral therapy, particularly the
      introduction of highly active antiretroviral therapy in 1996, many of these
      outward manifestations of the disease became rare. Ironically, however, the
      treatments used to control HIV infection (and its visible markers) have
      themselves been associated with appearance-related side effects. Patients may
      develop changes in fat distribution, rashes, skin hyperpigmentation, or
      paronychia. These effects not only have cosmetic and psychological consequences
      but also may decrease adherence to therapy, potentially causing regimen failure
      and drug resistance. Newer antiretroviral agents offer improved potency, more
      convenient dosing, and more treatment options with the potential for fewer side
      effects and drug interactions, which should foster optimal adherence by the
      patient. However, these newer drugs are also associated with appearance-related
      side effects, which must be considered in the selection of treatment regimens.
      This paper reviews the appearance-related side effects associated with classes of
      antiretroviral drugs as well as individual agents, including the newer
      antiretrovirals.

PMID- 16426153
TI  - Psychometric properties of a lipodystrophy scale.
AB  - Prior HIV lipodystrophy (LD) scales have been unidimensional, often combining
      changes of fat loss with fat accumulation with retinoid changes. Our objective
      was to determine the psychometric properties of a LD scale used in an outpatient
      LD subspecialty clinic at a university hospital HIV clinic. A patient and
      clinician self-administered LD scale was used to evaluate 107 patients referred
      to the Owen LD Clinic from March of 1999 to August of 2002. Sixteen measures of
      the LD syndrome were assessed on a severity scale ranging from 0 (none) to 3
      (severe). SPSS was used to perform a reliability and factor analysis. A total of
      150 paired patient and clinician assessments were performed. Thirty-one patients
      had repeat assessments. Reliability analysis of the patient and clinician self
      administered LD scale revealed an alpha of 0.76 and 0.73, respectively. Factor
      analysis of patient self-assessment of LD identified 3 factors, which clustered
      in the following order: fat loss, fat accumulation, and retinoid changes. Factor
      analysis of clinician self-assessment of LD identified 4 factors. The first
      factor clustered around items of fat loss. A second cluster consisted of retinoid
      changes. The final 2 factors clustered around items consistent with fat
      accumulation. The patient and clinician self-administered Owen Clinic LD scale
      was found to be highly reliable and useful in the assessment of LD. Our analysis
      confirms clinical intuition that the evaluation of LD is a multidimensional
      construct and that 3 subscales may be used to evaluate dimensions of fat loss,
      fat accumulation, and retinoid changes.

PMID- 16426154
TI  - The disclosure model versus a developmental illness experience model for children
      and adolescents living with HIV/AIDS in Sao Paulo, Brazil.
AB  - Whether, how, and when children's HIV/AIDS diagnosis needs to be disclosed to
      them has received growing attention. This paper describes and conceptualizes how
      communication about HIV/AIDS influences disease knowledge and psychosocial
      development in a group of children and adolescents living with perinatally
      acquired HIV infection in an AIDS institution in Sao Paulo, Brazil. Data consist
      of the lived experience of 36 children ages 1 to 15 and was gathered through
      ethnographic research methodologies: participant observation and semistructured
      informal interviews. Results show that AIDS diagnosis is not disclosed to
      children, who experience a growing confusion about the interconnected meanings of
      sickness, medications, living at a house/institution, and having AIDS. Children
      younger than 6 learn to accept medication taking and to silence illness-related
      questions. Seven to 9-year olds perceive that the word AIDS and/or being sick are
      considered negative attributes, but are confused about how these relate to their
      lives. Preadolescents' growing awareness of the relationship between their lives
      and negative social values associated with AIDS produces shame and anger.
      Adolescents exhibit a poor understanding of the implications of HIV/AIDS for
      their lives and cynicism toward AIDS care, their future, and information about
      risks to their health. In conclusion, lack of communication about HIV/AIDS
      creates a context of confusion and mistrust, is detrimental to psychosocial
      development and coping, compromises disease knowledge, and increases
      vulnerability to risk behavior. Providing developmentally appropriate information
      about HIV/AIDS that matches children's illness experiences at all ages would
      eliminate the need for disclosure and reduce children's emotional distress.

PMID- 16426152
TI  - Reframing "prevention with positives": incorporating counseling techniques that
      improve the health of HIV-positive patients.
AB  - Federal HIV prevention strategy seeks to increase efforts by health care
      providers to identify and reduce their HIV-positive patients' transmission
      related behaviors. Implementation of these recommendations will be hindered if
      providers perceive these efforts have the potential to harm their relationships
      with patients. Because transmission-related behaviors (unsafe sex and sharing
      needles) and the related issues of drug and alcohol use also jeopardize the
      health of HIV-positive patients, providers can use patient-centered counseling
      when addressing those behaviors. We suggest efforts to increase provider
      delivered transmission-prevention counseling be reframed so that "prevention with
      positives" includes the goal of protecting HIV-positive patients' health. We
      review the specific consequences of these risky behaviors on HIV-positive
      patients' health and review brief counseling strategies appropriate for HIV care
      providers.

PMID- 16426155
TI  - Psychosocial factors and medication adherence in HIV-positive youth.
AB  - The purpose of this study was to test variables consistently identified in the
      adult HIV literature as predictors of adherence (self-efficacy, social support,
      and psychological distress) in a sample of 24 HIV-positive youth (ages 16-24).
      Self-efficacy and psychological distress were significantly correlated with
      adherence but social support was not. Social support specific to taking
      medications was correlated with self-efficacy. In regression analysis, both self
      efficacy and psychological distress were independently related to adherence and
      together accounted for 47% of the variance. Results suggest the potential of
      mental health interventions that boost self-efficacy and reduce psychological
      distress but require replication with larger samples.

PMID- 16426156
TI  - Long-term adherence to first-line highly active antiretroviral therapy in a
      hospital-based cohort: predictors and impact on virologic response and relapse.
AB  - A high level of adherence to highly active antiretroviral therapy (HAART) is
      essential to minimize the risk of treatment failure and HIV disease progression.
      This cohort study evaluated the prevalence and predictors of long-term adherence
      with first-line HAART in a hospital-based unselected sample of HIV patients from
      central Italy, and examined the association between adherence and virological
      response or relapse. Between July 1996 and June 2004, 171 patients (67.3% males;
      mean age, 41.2 years) were followed for at least 24 weeks and up to 8 years.
      Adherence was measured by patient self-reports and confirmed using pharmacy
      records. The prevalence of high-level adherence (>or=90%) at 6 months was 88.3%;
      slightly less than 80% at 12 months. The incidence of adherence failure in the
      sample remained fairly stable until 24 months of follow-up, then it declined
      about 5% every 6 months. Cox analysis showed that compared to single/separated
      patients, homeless and married persons were, respectively, 1.95 times more likely
      and two times less likely to experience adherence failure (p < 0.05). The
      adjusted risk of adherence failure among patients who did not suffer drug-related
      toxicity was 0.57 (p < 0.05). Medication adherence was significantly associated
      with shorter time to virological response and longer time to relapse. Adherents
      were 1.69 times more likely to achieve viral suppression and nine times less
      likely to experience relapse than nonadherents (p < 0.01). Efforts at improving
      adherence should be prolonged for at least 24 months. A protective role of
      marriage for adherence failure is promising but requires confirmation in further
      research, that should also clarify the exact mechanisms determining the
      association.

PMID- 16426157
TI  - Ryan White Title I Survey: services for HIV-positive substance users.
AB  - People living with HIV/AIDS who are also substance users need primary health
      care, substance abuse treatment, and support services. They also require care
      delivery strategies that are comprehensive and innovative. Forty-three of 51 Ryan
      White Care Act Title I grantees funding 197 substance abuse treatment agencies in
      the United States participated in this study. Grantees were surveyed to determine
      (1) use of Title I funding to provide services for HIV-positive substance users,
      (2) the types of substance abuse services provided, (3) strengths and weaknesses
      of different metropolitan substance abuse service delivery systems, (4) sources
      of information used to assess the needs of substance users, (5) gaps in knowledge
      about substance users and their service needs, and (6) examples of successful
      strategies within the eligible metropolitan areas. The results of the study
      demonstrate that most grantees use Title I funds to support some form of
      substance abuse treatment for people with HIV; however, many do not use the funds
      to address the barriers to care that they identified. Lack of provider knowledge,
      expertise, and awareness, were cited as important barriers to care by a majority
      of the grantees. The availability of harm reduction approaches to care is an area
      in which there is wide variation. Several Title I programs have supported
      innovative programs for HIV positive substance users that may be used elsewhere
      as program models. It is important to find ways to incorporate these issues into
      the needs assessment and service prioritization process.

PMID- 16426160
TI  - Hoping for the best, preparing for the worst.

PMID- 16426161
TI  - Questions location of Plum Island facility.

PMID- 16426162
TI  - What is your diagnosis? Chronic bronchointerstitial pneumonia.

PMID- 16426164
TI  - Stress-related behaviors among horses used in a therapeutic riding program.
AB  - OBJECTIVE: To determine whether therapeutic riding resulted in higher levels of
      stress or frustration for horses than did recreational riding and whether
      therapeutic riding with at-risk individuals was more stressful for the horses
      than was therapeutic riding with individuals with physical or emotional
      handicaps. DESIGN: Observational study. ANIMALS: 14 horses in a therapeutic
      riding program. PROCEDURE: An ethogram of equine behaviors was created, and
      horses were observed while ridden by 5 groups of riders (recreational riders,
      physically handicapped riders, psychologically handicapped riders, at risk
      children, and special education children). Number of stress-related behaviors
      (ears pinned back, head raised, head turned, head tossed, head shaken, head down,
      and defecation) was compared among groups. RESULTS: No significant differences in
      mean number of stress-related behaviors were found when horses were ridden by
      recreational riders, physically handicapped riders, psychologically handicapped
      riders, or special education children. However, mean number of stress-related
      behaviors was significantly higher when horses were ridden by the at-risk
      children. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for horses in
      a therapeutic riding program, being ridden by physically or psychologically
      handicapped individuals is no more stressful for the horses than is being ridden
      in the same setting by recreational riders. However, at-risk children caused more
      stress to the horses, suggesting that the time horses are ridden by at-risk
      children should be limited both daily and weekly.

PMID- 16426163
TI  - What is your diagnosis? Tricuspid valve endocarditis.

PMID- 16426165
TI  - Effects of a therapeutic riding program on at-risk and special education
      children.
AB  - OBJECTIVE: To determine the effects of a therapeutic riding program on
      psychosocial measurements among children considered at risk for poor performance
      or failure in school or life and among children in special education programs.
      DESIGN: Observational study. POPULATION: 17 at-risk children (6 boys and 11
      girls) and 14 special education children (7 boys and 7 girls). PROCEDURE: For the
      at-risk children, anger, anxiety, perceived self-competence, and physical
      coordination were assessed. For the special education children, anger and
      cheerfulness were measured, and the children's and their mothers' perceptions of
      the children's behavior were assessed. Measurements were made before and after an
      8-session therapeutic riding program. RESULTS: For boys enrolled in the special
      education program, anger was significantly decreased after completion of the
      riding program. The boys' mothers also perceived significant improvements in
      their children's behavior after completion of the program. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that an 8-session therapeutic riding program
      can significantly decrease anger in adolescent boys in a special education
      program and positively affect their mothers' perception of the boys' behavior.

PMID- 16426166
TI  - Prevention of central sensitization and pain by N-methyl-D-aspartate receptor
      antagonists.

PMID- 16426167
TI  - Inheritance of rupture of the cranial cruciate ligament in Newfoundlands.
AB  - OBJECTIVE: To determine prevalence, level of inbreeding, heritability, and mode
      of inheritance for rupture of the cranial cruciate ligament (RCCL) in
      Newfoundlands. DESIGN: Retrospective and recruitment study. ANIMALS: 574 client
      owned Newfoundlands. PROCEDURE: Medical records from January 1, 1996, to December
      31, 2002, were evaluated for prevalence of RCCL. A pedigree was constructed by
      use of recruited Newfoundlands with RCCL status based on results of veterinary
      examination; level of inbreeding, heritability, and mode of inheritance were
      calculated. RESULTS: Hospital prevalence for RCCL was 22%; dogs in the pedigree
      from the recruitment study had a mean level of inbreeding of 1.19 x 10(4),
      heritability of 0.27, and a possible recessive mode of inheritance with 51%
      penetrance for RCCL. CONCLUSIONS AND CLINICAL RELEVANCE: Identification of a
      genetic basis for RCCL in Newfoundlands provided evidence that investigators can
      now focus on developing methods to identify carriers to reduce the prevalence of
      RCCL.

PMID- 16426168
TI  - Evaluation of signs of postoperative pain and complications after forelimb
      onychectomy in cats receiving buprenorphine alone or with bupivacaine
      administered as a four-point regional nerve block.
AB  - OBJECTIVE: To evaluate signs of postoperative pain and complications after
      forelimb onychectomy in cats receiving buprenorphine alone or with bupivacaine
      administered as a 4-point regional nerve block. DESIGN: Prospective, randomized,
      double-blind clinical trial. ANIMALS: 20 cats. PROCEDURE: All cats received
      buprenorphine (0.01 mg/kg [0.004 mg/lb], IM) preoperatively. One forelimb of each
      cat also received bupivacaine (1 mg/kg [0.45 mg/lb] of a 0.75% solution)
      administered as a 4-point regional nerve block. After onychectomy, discomfort
      (lameness, foot reaction, and pain) scores were evaluated by 2 experienced
      observers 2, 4, 6, 8, 24, and 168 hours postoperatively. Complication
      (hemorrhage, swelling, and infection) scores were evaluated 24 and 168 hours
      postoperatively. Surgeries were performed by 1 experienced veterinary surgeon.
      Rescue analgesia was provided if needed. RESULTS: 6 cats required rescue
      analgesia postoperatively. There was no difference in discomfort or complication
      scores between control limbs and limbs in which a nerve block was administered.
      Additionally, there was no difference in discomfort and complication scores
      between cats that did or did not require rescue analgesia. CONCLUSIONS AND
      CLINICAL RELEVANCE: Bupivacaine administered as a 4-point regional nerve block in
      addition to a systemic analgesic did not decrease discomfort or complication
      scores in cats undergoing forelimb onychectomy.

PMID- 16426169
TI  - Resection and use of a cyclooxygenase-2 inhibitor for treatment of pancreatic
      adenocarcinoma in a cockatiel.
AB  - CASE DESCRIPTION: A 5-year-old sexually intact male cockatiel was examined
      because of progressive dyspnea of 1 week's duration. CLINICAL FINDINGS: On
      auscultation of the lungs and air sacs, crackles were detected; the abdomen was
      distended and fluctuant on palpation. Eleven milliliters of clear yellow fluid
      was collected via abdominocentesis. Radiography (with and without contrast
      medium) and ultrasonography revealed a soft tissue mass in the caudoventral
      portion of the coelom. TREATMENT AND OUTCOME: Exploratory surgery of the coelomic
      cavity was performed and the neoplasm was excised. Histologic examination of the
      neoplasm was consistent with a high-grade pancreatic exocrine adenocarcinoma.
      Celecoxib, a cyclooxygenase (COX)-2 inhibitor, was administered for pain
      management and for potential antineoplastic activity. For 4.5 months after
      surgery, the bird had no recurrence of clinical signs; however, dyspnea recurred
      and during evaluation, the bird died. Necropsy findings indicated that the
      pancreatic adenocarcinoma had metastasized to surrounding tissues and vessels,
      which was not unexpected given the high grade assigned to the neoplasm during
      histologic analysis. CLINICAL RELEVANCE: Pancreatic neoplasms are associated with
      a poor prognosis, regardless of treatment modality. Celecoxib can be administered
      as palliative treatment to affected birds, but as with any nonsteroidal anti
      inflammatory drug, COX-2 inhibitors should be used cautiously because they can
      adversely affect renal function by decreasing renal prostaglandin synthesis.

PMID- 16426170
TI  - Long-term complications after phacoemulsification for cataract removal in dogs:
      172 cases (1995-2002).
AB  - OBJECTIVE: To determine common postoperative complications and risk factors for
      development of postoperative glaucoma or failure to preserve vision after
      phacoemulsification for cataract removal in dogs. Design-Retrospective case
      series. ANIMALS: 172 dogs (290 eyes) that underwent phacoemulsification surgery
      for cataract removal. PROCEDURE: Medical records were reviewed for postoperative
      complications; prevalence rates for each complication were calculated for follow
      up periods of 3 months, > 3 to 6 months, > 6 months to 1 year, > 1 to 2 years, >
      2 to 3 years, > 3 to 4 years, and > 4 years. Odds ratios for breed, age, sex,
      cataract hypermaturity, lens-induced uveitis, and diabetes mellitus were
      determined with respect to glaucoma and failure (ie, blindness, enucleation, or
      evisceration). RESULTS: The most common complication was mild posterior capsule
      opacification. Retinal detachment was uncommon (1% to 2%) for all time periods.
      Prevalence of glaucoma increased with time, although it remained < 10% until
      after the 1-year follow-up period. Boston Terriers, Cocker Spaniels, Cocker
      Spaniel-Poodle crosses, and Shih Tzus had increased risk of developing glaucoma.
      Eyes with hypermature cataracts were more likely to develop glaucoma. Prevalence
      of failure increased with time, although it remained < 10% until after the 3-year
      follow-up period. Cocker Spaniel-Poodle cross and Shih Tzus were more likely to
      have failure. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of breed and
      cataract hypermaturity may aid in the selection of patients. The increasing
      prevalence of postoperative complications with time indicated that longterm
      monitoring is warranted.

PMID- 16426172
TI  - Evaluation of clinical characteristics and bacterial isolates in dogs with
      bacterial keratitis: 97 cases (1993-2003).
AB  - OBJECTIVE: To evaluate clinical characteristics and breeds affected with
      bacterial keratitis and compare patterns of resistance in bacterial isolates over
      time in dogs. DESIGN: Retrospective cross-sectional study. ANIMALS: 97 dogs with
      bacterial keratitis. PROCEDURE: Dogs with bacterial keratitis were identified
      from teaching hospital medical records at the Universities of Tennessee and
      Florida during the years 1993 to 2003. Data were collected pertaining to breed,
      Schirmer tear test results, treatments administered at the time of initial
      examination, bacterial species isolated, and resistance to selected
      antimicrobials. RESULTS: 66% of the dogs were brachycephalic, 54% had tear
      production < 15 mm/min, and 29% were receiving a corticosteroid at the time of
      initial examination. The most common bacteria isolated were Staphylococcus
      intermedius (29%), beta-hemolytic Streptococcus spp (17%), and Pseudomonas
      aeruginosa (21%). Staphylococcus intermedius isolates had limited resistance to
      certain antimicrobials. More than 80% of beta-hemolytic Streptococcus spp
      isolates were resistant to neomycin, polymyxin B, and tobramycin. Isolates of P
      aeruginosa were susceptible to tobramycin and gentamicin and had limited
      resistance to ciprofloxacin and enrofloxacin. Among bacterial species isolated,
      there was no evidence of development of antimicrobial resistance over time.
      CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that administration of
      ciprofloxacin or a combination of a first-generation cephalosporin and tobramycin
      may be used in the treatment of bacterial keratitis while awaiting results of
      bacterial culture and susceptibility testing. Evidence suggests that current
      methods of medical management of bacterial keratitis are not associated with
      increased antimicrobial resistance.

PMID- 16426174
TI  - Evaluation of lung lobe torsion in Pugs: 7 cases (1991-2004).
AB  - OBJECTIVE: To determine whether there is a predis-position for lung lobe torsion
      (LLT) in Pugs and describe clinical findings associated with LLT in that breed,
      compared with findings in other breeds. DESIGN: Retrospective case series.
      ANIMALS: 7 Pugs and 16 dogs of other breeds. PROCEDURE: Information collected
      from records included signalment, history, lung lobe affected, results of
      clinicopathologic testing, histologic findings, diagnostic imaging results,
      surgical treatment, and outcome. RESULTS: 23 dogs were diagnosed with LLT, 10 of
      which were large-breed dogs and 13 of which were small-breed dogs. Seven of the
      small-breed dogs were Pugs. Pugs with LLT were significantly overrepresented,
      compared with the general hospital population. Affected Pugs ranged in age from
      4.5 months to 4 years (median, 1.5 years). Six of the 7 Pugs had no predisposing
      conditions, and 6 were male. Six Pugs survived to discharge. Of the other small-
      and large-breed dogs, 3 of 6 and 5 of 10 survived to discharge, respectively.
      None of the Pugs were readmitted for complications or recurrence. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated that young male Pugs may be predisposed to
      developing spontaneous LLT. The prognosis for survival and resolution of clinical
      signs in Pugs with LLT appeared to be excellent. Factors contributing to the
      development of LLT in Pugs are not known.

PMID- 16426175
TI  - Evaluation of prognostic factors associated with outcome in dogs with multiple
      cutaneous mast cell tumors treated with surgery with and without adjuvant
      treatment: 54 cases (1998-2004).
AB  - OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with
      multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without
      adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a
      minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been
      excised and had adequate staging and follow-up data. PROCEDURE: Medical records
      from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier
      product-limit method and log-rank analysis. Prognostic factors evaluated included
      signalment; number, histologic grade, location, size, local recurrence, and de
      novo development of MCTs; quality of surgical margins; clinical signs at the time
      of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs
      with 153 tumors were included. Median follow-up time was 658 days. Median disease
      free interval (1,917 days; range, 11 to 1,917 days) and median survival time
      (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to
      5-year survival rates were 87% and 85%, respectively. The overall rate of
      metastasis was 15%. Factors that negatively influenced survival time in the
      univariate analysis included incomplete excision, local recurrence, size > 3 cm,
      clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence
      of clinical signs at the time of diagnosis was the only negative prognostic
      factor for disease-free interval detected in the multivariate analysis.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous
      MCTs in dogs are associated with a low rate of metastasis and a good prognosis
      for long-term survival with adequate excision of all MCTs.

PMID- 16426177
TI  - Evaluation of the association between spondylosis deformans and clinical signs of
      intervertebral disk disease in dogs: 172 cases (1999-2000).
AB  - OBJECTIVE: To evaluate the association between spondylosis deformans and clinical
      signs of intervertebral disk disease (IVDD) in dogs. DESIGN: Retrospective case
      series. ANIMALS: 210 dogs. PROCEDURE: Records of 172 dogs with clinical signs of
      IVDD and 38 dogs with other neurologic disorders were reviewed. Signalment, sites
      of spondylosis, severity of associated osteophytosis, type of disk herniation,
      and duration of signs were recorded. RESULTS: Dogs with IVDD had significantly
      fewer sites of involvement and lower grades of spondylosis deformans, compared
      with those in the non-IVDD group. When groups were adjusted for age and weight
      via multivariate linear regression, there were no differences in severity of
      osteophytosis or number of affected sites. Dogs with type II disk disease had
      higher numbers of affected sites and more severe changes, compared with dogs with
      type I disk herniation. There was no difference between groups in the rate at
      which IVDD was diagnosed at sites of spondylosis, compared with the rate at which
      IVDD was diagnosed in unaffected disk spaces. Areas of spondylosis were closer to
      sites of IVDD that elicited clinical signs than to randomly chosen intervertebral
      spaces, and distances between sites of spondylosis and sites of IVDD had a
      bimodal appearance. CONCLUSIONS AND CLINICAL RELEVANCE: An association may exist
      between radiographically apparent spondylosis and type II disk disease; type I
      disk disease was not associated with spondylosis. Spondylosis in radiographs of
      dogs with suspected type I disk disease is not clinically important. Spatial
      associations among sites of spondylosis and sites of IVDD may be coincidental or
      associated with vertebral column biomechanics.

PMID- 16426178
TI  - Pyrantel pamoate resistance in horses receiving daily administration of pyrantel
      tartrate.
AB  - CASE DESCRIPTIONS: 16 horses treated daily with pyrantel tartrate (2.64 mg/kg
      [1.2 mg/lb], PO) as part of a prophylactic anthelmintic program. CLINICAL
      FINDINGS: Fecal worm egg counts (FWECs) were obtained on all 16 horses. Mean FWEC
      was 478 eggs/g (epg; range, 0 to 4,075 epg). Three of the 16 horses were
      responsible for 85% of the total fecal egg output for the herd on the day of
      sampling. Six horses had FWECs < 200 epg. Three horses that had arrived within 4
      months of the sampling date had FWECs < 100 epg. TREATMENT AND OUTCOME: An FWEC
      reduction test was initiated the day after FWECs were obtained; all horses with
      FWECs > 100 epg (9 horses) were treated with pyrantel pamoate (6.6 mg/kg [3
      mg/lb], PO), and 14 days later, the FWEC was repeated. During the 14-day period,
      all horses received pyrantel tartrate (2.64 mg/kg, PO) daily. Fecal worm egg
      count reduction was calculated for each horse. Mean FWEC reduction for the group
      was 28.5% (range, increase of 21% in FWECs 14 days after treatment to a decrease
      of 100% in FWEC 14 days after treatment). CLINICAL RELEVANCE: Farms should be
      monitored for cyathostomes resistant to pyrantel pamoate prior to use of pyrantel
      tartrate. Fecal worm egg counts should be monitored routinely in horses before
      and after treatment to ensure efficacy of cyathostome control measures.

PMID- 16426181
TI  - Professional overhead expense insurance.

PMID- 16426180
TI  - Lobomycosis in Atlantic bottlenose dolphins from the Indian River Lagoon,
      Florida.
AB  - OBJECTIVE: To determine the prevalence of lobomycosis, a mycotic infection of
      dolphins and humans caused by a yeastlike organism (Lacazia loboi), among
      dolphins in the Indian River Lagoon in Florida. DESIGN: Cross-sectional study.
      ANIMALS: 146 Atlantic bottlenose dolphins. PROCEDURE: Comprehensive health
      assessments of bottlenose dolphins in the Indian River Lagoon of Florida (n = 75)
      and in estuarine waters near Charleston, SC (71), were conducted during 2003 and
      2004. Bottlenose dolphins were captured, examined, and released. Skin lesions
      were photographed and then biopsied. Tissue sections were stained with H&E and
      Gomori methenamine silver stains for identification of L. loboi. RESULTS: 9 of 30
      (30%) dolphins captured in the southern portion of the Indian River Lagoon had
      lobomycosis, whereas none of the 45 dolphins captured in the northern portion of
      the lagoon or of the 71 dolphins captured near Charleston, SC, did. Affected
      dolphins had low serum alkaline phosphatase activities and high acute-phase
      protein concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      lobomycosis may be occurring in epidemic proportions among dolphins in the Indian
      River Lagoon. Localization of the disease to the southern portion of the lagoon,
      an area characterized by freshwater intrusion and lower salinity, suggests that
      exposure to environmental stressors may be contributing to the high prevalence of
      the disease, but specific factors are unknown. Because only dolphins and humans
      are naturally susceptible to infection, dolphins may represent a sentinel species
      for an emerging infectious disease.

PMID- 16426182
TI  - Comments on rehabilitators of rabies vector species.

PMID- 16426183
TI  - Making comparative medicine more so.

PMID- 16426184
TI  - What is your diagnosis? Spindle cell sarcoma .

PMID- 16426185
TI  - What is your diagnosis? Abdominally retained testis.

PMID- 16426186
TI  - Theriogenology question of the month. What are the 3 management options for a
      mare with twin fetuses at this stage of gestation?

PMID- 16426187
TI  - Evaluation of a two-centimeter lateral surgical margin for excision of grade I
      and grade II cutaneous mast cell tumors in dogs.
AB  - OBJECTIVE: To evaluate completeness of excision and clinical outcome in dogs with
      cutaneous mast cell tumors (MCTs) excised with a lateral margin of 2 cm and a
      deep margin of 1 fascial plane. DESIGN: Prospective study. ANIMALS: 16 client
      owned dogs with 1 or more cutaneous MCTs. PROCEDURE: Excision of MCTs was
      performed with a 2-cm lateral margin and a deep margin of 1 fascial plane.
      Histologic tumor grading was performed; surgical margins were categorized as
      complete or incomplete. Follow-up information was obtained via repeat examination
      of the dogs by veterinarians or client-completed questionnaires. RESULTS: 4 grade
      I and 19 grade II cutaneous MCTs were evaluated. Overall, 21 (91%) MCTs were
      completely excised; 2 grade II tumors had foci of mast cells at the 2-cm margin.
      Two dogs received adjunctive treatments following surgery. Follow-up information
      was available for all dogs (median follow-up period, 379 days; range, 51 to 538
      days); no local recurrence was detected during this time. De novo MCTs were
      detected in 3 of 16 dogs at 37, 54, and 154 days after surgery. Via Kaplan-Meier
      analysis, median survival time and disease-free interval were both > 538 days
      (medians not yet reached). No prognostic variables were identified. CONCLUSIONS
      AND CLINICAL RELEVANCE: Excision with a 2-cm lateral margin and a deep margin of
      1 fascial plane may result in satisfactory excision of grades I and II MCTs in
      dogs, with recurrence rates similar to those reported previously. Use of these
      margins may minimize complications associated with larger local tumor resection.

PMID- 16426189
TI  - Distribution of Malassezia organisms on the skin of unaffected psittacine birds
      and psittacine birds with feather-destructive behavior.
AB  - OBJECTIVE: To ascertain whether Malassezia organisms can be detected via
      cytologic examination and fungal culture of samples from the skin surface of
      psittacine birds and determine whether the number of those organisms differs
      between unaffected psittacines and those that have chronic feather-destructive
      behavior or differs by body region. DESIGN: Prospective study. ANIMALS: 50
      unaffected psittacines and 53 psittacines that had feather-destructive behavior.
      PROCEDURE: Samples were collected by use of acetate tape strips from the skin of
      the head, neck, proventer, propatagium, inguinal region, and preen gland area of
      each bird; 0.5-cm(2) sample areas were examined microscopically for yeast, and
      samples were also incubated on Sabouraud dextrose agar. Polymerase chain reaction
      assays specific for Malassezia spp, saprophytic fungi, and Candida albicans were
      performed on DNA prepared from cultured colonies; nested PCR evaluation for
      Malassezia pachydermatis was then performed. RESULTS: Microscopically, 63 of 618
      (10%) tape-strip samples contained yeast. Thirty cultured colonies were assessed
      via PCR assays, and all yielded negative results for Malassezia spp; C albicans
      was identified in 2 colony samples. The numbers of yeast identified
      microscopically in psittacines with feather-destructive behavior and in
      unaffected birds did not differ significantly, and numbers did not differ by body
      region. CONCLUSIONS AND CLINICAL RELEVANCE: Yeast were identified infrequently
      via cytologic examination of samples from the skin surface of unaffected
      psittacine birds or those that had chronic feather-destructive behavior. If yeast
      are identified on the skin of birds with feather-destructive behaviors, fungal
      culture of skin samples should be performed to identify the organism.

PMID- 16426191
TI  - Serum alkaline phosphatase activity in Scottish Terriers versus dogs of other
      breeds.
AB  - OBJECTIVE: To determine whether Scottish Terriers have higher serum alkaline
      phosphatase (ALP) activities and a higher prevalence of diseases commonly
      associated with high serum ALP activity than do dogs of other breeds. DESIGN:
      Retrospective case-control study. ANIMALS: 85 Scottish Terriers and 340 age
      matched control dogs that were not Scottish Terriers. PROCEDURE: Medical records
      were reviewed, and data for year of evaluation, age, sex, breed, serum ALP
      activity, and final diagnosis were recorded. RESULTS: Scottish Terriers had a
      significantly higher mean serum ALP activity than did control dogs (1,520 U/L vs
      306 U/L). Regardless of breed, dogs that had a disease commonly associated with
      high serum ALP activity had a significantly higher mean serum ALP activity than
      did dogs without such diseases (1,304 U/L vs 427 U/L). Scottish Terriers were 2.4
      times as likely to have a disease commonly associated with high serum ALP
      activity than were control dogs, but Scottish Terriers with diseases commonly
      associated with high serum ALP activity had a significantly higher mean ALP
      activity than did control dogs with such diseases (2,073 U/L vs 909 U/L), and
      Scottish Terriers without such diseases had a significantly higher mean serum ALP
      activity than did control dogs without such diseases (1,349 U/L vs 228 U/L).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that Scottish Terriers have
      higher serum ALP activities than do dogs of other breeds. Although Scottish
      Terriers also have a higher prevalence of diseases associated with high serum ALP
      activity, this alone did not explain the higher mean serum ALP activity in the
      breed.

PMID- 16426194
TI  - Fecal incontinence associated with epidural spinal hematoma and intervertebral
      disk extrusion in a dog.
AB  - CASE DESCRIPTION: A 7-year-old castrated male Great Dane was evaluated because of
      a 2-month history of fecal incontinence. CLINICAL FINDINGS: On the basis of the
      presence of paraparesis and apparently normal spinal reflexes, the neurologic
      signs were localized in the region of the third thoracic to the third lumbar
      spinal cord segments. On the basis of the findings of magnetic resonance imaging,
      a presumptive diagnosis of a compressive intervertebral disk extrusion with
      secondary hemorrhage and epidural hematoma formation was made. TREATMENT AND
      OUTCOME: A right-sided hemil-aminectomy was performed (centered at the T13-L1
      intervertebral space) to further characterize the lesion and decompress the
      spinal cord. The histopathologic diagnosis was extruded intervertebral disk
      material with chronic hemorrhage and inflammation. Three weeks after surgery,
      there was complete resolution of the dog's fecal incontinence and moderate
      improvements in its hind limb function. CLINICAL RELEVANCE: Thoracolumbar spinal
      cord injuries can result in upper motor neuron fecal incontinence in ambulatory
      dogs. Epidural spinal hematomas may develop secondary to intervertebral disk
      herniations and cause spinal cord compression resulting in neurologic deficits.

PMID- 16426193
TI  - Effects of diet on clinical signs of exocrine pancreatic insufficiency in dogs.
AB  - OBJECTIVE: To assess the effects of dietary modification on clinical signs of
      exocrine pancreatic insufficiency (EPI) in dogs. DESIGN: Blinded randomized
      crossover study. ANIMALS: 21 dogs with EPI. PROCEDURE: Dogs were fed the diet
      they received at home for 2 weeks. Thereafter, they received 3 special diets (a
      high-fat diet, a high-fiber diet, and a highly digestible low-residue diet) for 3
      weeks each. Owners scored dogs daily for the last 2 weeks of each 3-week period
      for severity of 6 clinical signs including appetite, defecation frequency,
      consistency of feces, borborygmus, flatulence, and coprophagia. An EPI index was
      calculated for each dog by adding the daily scores for each clinical sign.
      RESULTS: Significant differences in daily EPI indices among diets were observed
      in 20 dogs. The original diet appeared to be the most suitable in 8 dogs, whereas
      the high-fat diet was most suitable in 5 dogs, the high-fiber diet was most
      suitable in 4 dogs, and the low-residue diet was most suitable in 2 dogs. In 1
      dog, the lowest EPI index score was the same during the original diet and the
      high-fat diet feeding periods. One dog did not complete the feeding period for
      the high-fiber diet. Differences in mean EPI indices among diets were not
      significant. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that responses
      to different diets varied among individual dogs. Because responses to the feeding
      regimens were unpredictable, it is suggested that feeding regimens be
      individually formulated for dogs with EPI.

PMID- 16426196
TI  - Avian influenza A virus subtype H5N2 in a red-lored Amazon parrot.
AB  - CASE DESCRIPTION: A 3-month-old red-lored Amazon parrot (Amazona autumnalis
      autumnalis) was evaluated for severe lethargy. CLINICAL FINDINGS: Avian influenza
      virus hemagglutinin subtype H5N2 with low pathogenicity was characterized by
      virus isolation, real-time reverse transcriptase PCR assay, chicken intravenous
      pathogenicity index, and reference sera. The virus was also determined to be
      closely related to a virus lineage that had been reported only in Mexico and
      Central America. TREATMENT AND OUTCOME: The chick was admitted to the hospital
      and placed in quarantine. Supportive care treatment was administered. Although
      detection of H5 avian influenza virus in birds in the United States typically
      results in euthanasia of infected birds, an alternative strategy with strict
      quarantine measures and repeated diagnostic testing was used. The chick recovered
      from the initial clinical signs after 4 days and was released from quarantine 9
      weeks after initial evaluation after 2 consecutive negative virus isolation and
      real-time reverse transcriptase PCR assay results. CLINICAL RELEVANCE: To the
      authors' knowledge, this is the first report of H5N2 avian influenza A virus
      isolated from a psittacine bird and represents the first introduction of this
      virus into the United States, most likely by illegal importation of psittacine
      birds. Avian influenza A virus should be considered as a differential diagnosis
      for clinical signs of gastrointestinal tract disease in psittacine birds,
      especially in birds with an unknown history of origin. Although infection with
      avian influenza virus subtype H5 is reportable, destruction of birds is not
      always required.

PMID- 16426198
TI  - Liver lobe torsion in dogs: 13 cases (1995-2004).
AB  - OBJECTIVE: To determine history, results of diagnostic testing, surgical
      findings, complications, and outcome for dogs with liver lobe torsion (LLT).
      DESIGN: Retrospective case series. ANIMALS: 12 dogs (1 with 2 episodes).
      PROCEDURE: Signalment, clinical signs, clinicopathologic findings, radiographic
      and ultrasonographic findings, surgical and histologic findings, complications,
      and hospitalization time were evaluated. RESULTS: The most common clinical signs
      were nonspecific abnormalities (eg, vomiting, lethargy, and anorexia) of acute or
      chronic duration. All dogs were large-breed dogs (median body weight, 37.2 kg [82
      lb]). Biochemical abnormalities included high alanine amino-transferase (n = 12)
      and aspartate aminotransferase (11) activities. Results of abdominal
      ultrasonography were supportive of the diagnosis in 5 of 8 cases. Affected lobes
      included the left medial lobe (n = 4), left lateral lobe (3), papillary process
      of the caudate lobe (2), caudate lobe (1), and right lateral lobe (1).
      Exploratory celiotomy and liver lobectomy were performed in 12 of 13 cases, and
      in 11 of those 12 cases, the dog survived. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that development of nonspecific clinical signs of vomiting,
      lethargy, and anorexia in conjunction with high serum hepatic enzyme activities
      and mature neutrophilia in a medium-sized or large-breed dog should increase the
      index of suspicion for LLT. Abdominal ultrasonography with Doppler assessment may
      be useful in establishing the diagnosis. The long-term outcome for dogs that
      survive the hospitalization period is excellent.

PMID- 16426200
TI  - Effect of repeated transvaginal ultrasound-guided follicle aspiration on
      fertility in mares.
AB  - OBJECTIVE: To determine whether performance of transvaginal ultrasound-guided
      follicle aspiration (TVUFA) repeatedly in mares adversely affects their
      fertility. DESIGN: Historical prospective study. ANIMALS: 23 mares that had never
      undergone TVUFA and 59 mares that had undergone TVUFA on 1 to 11 occasions.
      PROCEDURE: Mares were classified into 4 groups according to the number of TVUFA
      procedures previously performed on the ovary in which ovulation occurred at the
      time of insemination as follows: group 1, 0 TVUFAs (control group, n = 23 mares);
      group 2, 1 or 2 TVUFAs (40 mare-cycles); group 3, 3 or 4 TVUFAs (21 mare-cycles);
      and group 4, 5 to 11 TVUFAs (13 mare-cycles). Each ovary and its associated
      number of TVUFAs were considered separately; therefore, some of the mares that
      underwent TVUFA were represented in > 1 group (1 mare was included in group 2
      twice [once for each ovary]), and the sample size in groups 2, 3, and 4 was
      denoted as mare-cycles. Fertility was assessed as pregnancy rates in cycles in
      which mares were inseminated with fresh or cooled semen from 1 fertile stallion.
      RESULTS: There were no significant differences in pregnancy rates among groups 1,
      2, 3, and 4 (83%, 90%, 81%, and 85%, respectively). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that repeated performance of TVUFA (as many as 11
      times) had no detectable adverse effect on fertility in mares. This finding is
      clinically important for situations when TVUFA is performed on fertile mares,
      whether for oocyte collection or other purposes.

PMID- 16426201
TI  - Intracranial abscess caused by Rhodococcus equi infection in a foal.
AB  - CASE DESCRIPTION: A 4-month-old Missouri Fox Trotter colt was examined for a 5
      week history of head tilt after treatment for suspected pulmonary Rhodococcus
      equi infection. CLINICAL FINDINGS: Computed tomography revealed osteolysis of the
      occipital, temporal, and caudal portion of the parietal bones of the left side of
      the cranium. A soft tissue mass compressing the occipital region of the cerebral
      cortex and cerebellum was associated with the osteolytic bone. TREATMENT AND
      OUTCOME: A rostrotentorial-suboccipital craniectomy approach was performed to
      remove fragmented occipital bone, debulk the intracranial mass, and obtain tissue
      samples for histologic examination and bacterial culture. All neurologic deficits
      improved substantially within 3 days after surgery. Bacterial culture of the
      resected soft tissue and bone fragments yielded R equi. CLINICAL RELEVANCE:
      Intracranial surgery in veterinary medicine has been limited to dogs and cats;
      however, in select cases, extrapolation of surgical techniques used in humans and
      small animals can assist with intracranial procedures in horses.

PMID- 16426202
TI  - Evaluation of the use of an on-farm system for bacteriologic culture of milk from
      cows with low-grade mastitis.
AB  - OBJECTIVE: To determine factors associated with implementation and use of an on
      farm system for bacteriologic culture of milk from cows with lowgrade mastitis,
      including information on how producers used the on-farm bacteriologic culture
      system to guide antimicrobial selection practices and the resulting impact on
      patterns of antimicrobial use. DESIGN: Retrospective cohort study. SAMPLE
      POPULATION: Producers of 81 dairy farms. PROCEDURE: Farms that used an on-farm
      system for bacteriologic culture of milk from January 2001 to July 2003 were
      surveyed. RESULTS: Over half of those producers continuing to use the on-farm
      culture delayed antimicrobial treatment pending results of bacteriologic culture.
      Most other producers initiated empirical antimicrobial treatment while
      bacteriologic culture results were pending. Several barriers to the use of an on
      farm system were identified. Significant reductions in rates of antimicrobial use
      were detected when comparing antimicrobial use rates before and during use of the
      on-farm system. Most producers chose to treat cows with mastitis caused by gram
      positive pathogens with antimicrobials, whereas treatment choices for cows with
      mastitis caused by gram-negative bacteria and in cases in which no growth was
      detected varied. CONCLUSIONS AND CLINICAL RELEVANCE: Readily available results
      permit antimicrobial selections to be made on the basis of the causative agent of
      mastitis. Adoption of an on-farm system for bacteriologic culture of milk may
      result in significant reductions in the percentage of cows treated with
      antimicrobials. Decreasing antimicrobial use may have several benefits including
      preventing unnecessary discarding of milk, decreasing the potential for drug
      residues in milk, and improving treatment outcomes as a result of targeted
      treatments.

PMID- 16426205
TI  - Analgesic effects of epidural administration of hydromorphone in horses.
AB  - OBJECTIVE: To evaluate the effects of epidural administration of hydromorphone on
      avoidance threshold to noxious electrical stimulation of the perineal, sacral,
      lumbar, and thoracic regions in horses. ANIMALS: 6 healthy adult horses.
      PROCEDURE: Horses were assigned to receive hydromorphone (0.04 mg/kg) or a
      control solution (20 mL of sterile water) administered epidurally into in the
      first intercoccygeal space. Treatments were administered at time intervals of >
      or = 7 days. Electrical stimulation was applied for 6 hours after epidural
      injection over the dermatomes of the perineal, sacral, lumbar, and thoracic
      regions, and the avoidance threshold voltage was recorded. RESULTS:
      Administration of sterile water did not change the avoidance threshold.
      Hydromorphone significantly increased the avoidance threshold by 20 minutes after
      injection, which lasted until 250 minutes after epidural administration in the
      perineal, sacral, lumbar, and thoracic regions. Profound analgesia (avoidance
      threshold > 40 V) was achieved only in the perineal region at 60 minutes after
      epidural administration of hydromorphone. Analgesia for all dermatomes was
      considered moderate for 250 minutes after epidural injection. CONCLUSIONS AND
      CLINICAL RELEVANCE: Epidural administration of hydromorphone increases the
      avoidance threshold to noxious electrical stimulation in the perineal, lumbar,
      sacral, and thoracic regions in horses for 250 minutes after injection.
      Hydromorphone epidural administration may prove useful in the management of
      horses with pain of moderate to mild intensity.

PMID- 16426206
TI  - Effects of intravenous administration of lidocaine on the thermal threshold in
      cats.
AB  - OBJECTIVE: To determine the effects of IV administration of lidocaine on thermal
      antinociception in conscious cats. ANIMALS: 6 cats. PROCEDURE: 2 experiments were
      performed in each cat (interval of at least 2 months). In experiment 1, lidocaine
      pharmacokinetics were determined for each conscious cat following IV
      administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from
      experiment 1 were used to calculate appropriate doses of lidocaine that would
      achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or
      an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was
      administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1,
      2, 5, and 8 microg/mL. Skin temperature and thermal threshold were determined at
      the start of the experiment (baseline) and at each concentration. Samples of
      venous blood were obtained at each target concentration for plasma lidocaine
      concentration determination. RESULTS: In experiment 2, actual plasma lidocaine
      concentrations were 0.00 +/- 0.00 microg/mL, 0.25 +/- 0.18 microg/mL, 0.57 +/-
      0.20 microg/mL, 1.39 +/- 0.13 microg/mL, 2.33 +/- 0.45 microg/mL, and 4.32 +/-
      0.66 microg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8
      microg/mL, respectively. Compared with baseline values, no significant change in
      skin temperature or thermal threshold was detected at any lidocaine plasma
      concentration (or saline solution equivalent). Skin temperature or thermal
      threshold values did not differ between lidocaine or control treatments.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that these moderate plasma
      concentrations of lidocaine did not affect thermal antinociception in cats.

PMID- 16426207
TI  - Effect of intravenous administration of ketamine on the minimum alveolar
      concentration of isoflurane in anesthetized dogs.
AB  - OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the
      minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs.
      PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and
      the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs
      after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the
      same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV
      infusion device was used to administer ketamine and to achieve plasma ketamine
      concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained
      from experiment 1. The MAC of isoflurane was determined at each plasma ketamine
      concentration, and blood samples were collected for ketamine and norketamine
      concentration determination. RESULTS: Actual mean +/- SD plasma ketamine
      concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/-
      0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/-
      25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11
      microg/mL, respectively. At these plasma concentrations, isoflurane MAC was
      reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to
      78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in
      isoflurane MAC was significant, and the response had a linear and quadratic
      component. Salivation, regurgitation, mydriasis, increased body temperature, and
      spontaneous movements were some of the adverse effects associated with the high
      plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine
      appears to have a potential role for balanced anesthesia in dogs.

PMID- 16426208
TI  - Influence of metoclopramide on gastroesophageal reflux in anesthetized dogs.
AB  - OBJECTIVE: To determine the effect of 2 doses of metoclopramide on the incidence
      of gastroesophageal reflux (GER) in anesthetized dogs. ANIMALS: 52 healthy dogs
      undergoing elective orthopedic surgery. PROCEDURE: In this prospective clinical
      study, dogs were evaluated before and during orthopedic surgery. The anesthetic
      protocol used was standardized to include administration of acepromazine,
      morphine, thiopental, and isoflurane. Dogs were randomly selected to receive an
      infusion of saline (0.9% NaCl) solution, a low dose of metoclopramide, or a high
      dose of metoclopramide before and during anesthesia. Treatment groups were
      similar with respect to age, body weight, duration of food withholding before
      surgery, duration of surgery, and dose of thiopental administered. Dogs were
      positioned in dorsal recumbency during surgery. A sensor-tipped catheter was
      inserted to measure esophageal pH during anesthesia. We defined GER as a decrease
      in esophageal pH to < 4 or an increase to > 7.5 that lasted more than 30 seconds.
      RESULTS: The high dose of metoclopramide (bolus loading dose of 1.0 mg/kg, IV,
      followed by continuous infusion at a rate of 1.0 mg/kg/h) was associated with a
      54% reduction in relative risk of developing GER. The low dose did not
      significantly affect the incidence of GER. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of metoclopramide by bolus and constant rate infusion at doses
      much higher than commonly used will reduce the incidence but not totally prevent
      GER in anesthetized dogs undergoing orthopedic surgery.

PMID- 16426209
TI  - Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility
      effects and recovery characteristics of anesthesia with isoflurane and halothane
      in horses undergoing arthroscopic surgery.
AB  - OBJECTIVE: To compare hemodynamic, clinicopathologic, and gastrointestinal
      motility effects and recovery characteristics of halothane and isoflurane in
      horses undergoing arthroscopic surgery. ANIMALS: 8 healthy adult horses.
      PROCEDURE: Anesthesia was maintained with isoflurane or halothane (crossover
      study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables
      and related derived values were recorded. Recovery from anesthesia was assessed;
      gastrointestinal tract motility was subjectively monitored for 72 hours after
      anesthesia. Horses were administered chromium, and fecal chromium concentration
      was used to assess intestinal transit time. Venous blood samples were collected
      for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia.
      RESULTS: Compared with halothane-anesthetized horses, cardiac index, oxygen
      delivery, and heart rate were higher and systemic vascular resistance was lower
      in isoflurane-anesthetized horses. Mean arterial blood pressure and the
      dobutamine dose required to maintain blood pressure were similar for both
      treatments. Duration and quality of recovery from anesthesia did not differ
      between treatments, although the recovery periods were somewhat shorter with
      isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized
      earlier and intestinal transit time of chromium was shorter than that detected
      after halothane anesthesia. Compared with isoflurane, halothane was associated
      with increases in serum aspartate transaminase and glutamate dehydrogenase
      activities, but there were no other important differences in clinicopathologic
      variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with
      halothane, isoflurane appears to be associated with better hemodynamic stability
      during anesthesia, less hepatic and muscle damage, and more rapid return of
      normal intestinal motility after anesthesia in horses undergoing arthroscopic
      procedures.

PMID- 16426210
TI  - Effects of anatomic conformation on three-dimensional motion of the caudal lumbar
      and lumbosacral portions of the vertebral column of dogs.
AB  - OBJECTIVE: To determine the association between the 3-dimensional (3-D) motion
      pattern of the caudal lumbar and lumbosacral portions of the canine vertebral
      column and the morphology of vertebrae, facet joints, and intervertebral disks.
      SAMPLE POPULATION: Vertebral columns of 9 German Shepherd Dogs and 16 dogs of
      other breeds with similar body weights and body conditions. PROCEDURE: Different
      morphometric parameters of the vertebral column were assessed by computed
      tomography (CT) and magnetic resonance imaging. Anatomic conformation and the 3-D
      motion pattern were compared, and correlation coefficients were calculated.
      RESULTS: Total range of motion for flexion and extension was mainly associated
      with the facet joint angle, the facet joint angle difference between levels of
      the vertebral column in the transverse plane on CT images, disk height, and lever
      arm length. CONCLUSIONS AND CLINICAL RELEVANCE: Motion is a complex process that
      is influenced by the entire 3-D conformation of the lumbar portion of the
      vertebral column. In vivo dynamic measurements of the 3-D motion pattern of the
      lumbar and lumbosacral portions of the vertebral column will be necessary to
      further assess biomechanics that could lead to disk degeneration in dogs.

PMID- 16426211
TI  - Measurement of urinary glycosaminoglycans in dogs.
AB  - OBJECTIVES: To measure urine concentrations of sulfated glycosaminoglycans
      (GAGs), determine optimal storage conditions for urine samples, establish a
      reference range, and determine whether there is correlation between 24-hour total
      urine GAG excretion and the GAG-to-creatinine ratio (GCR). ANIMALS: 14 healthy
      adult dogs. PROCEDURE: Single urine sample GAG concentrations and GCRs were
      measured in samples collected from 14 healthy dogs at the start of the 24-hour
      collection period. Twenty-four-hour total urine GAG excretions were determined
      from urine collected during a 24-hour period in the same 14 dogs. Total sulfated
      GAG concentrations were also measured in urine from these dogs after the urine
      had been stored at 4 degrees C and -20 degrees C for 1, 7, and 30 days. RESULTS:
      Urine GAG concentrations were not significantly different from baseline values
      after urine was stored at 4 degrees C for up to 1 day and -20 degrees C for up to
      30 days. Neither single urine sample GAG concentration (R2, 0.422) nor GCR (R2,
      0.084) was an adequate predictor of 24-hour total urine GAG excretion.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study provide data that can
      be used to establish a reference range for 24-hour total urine GAG excretion in
      dogs and adequate conditions for sample storage. Contrary to findings in humans,
      there was no significant linear correlation between 24-hour total urine GAG
      excretion and single urine sample GCR in dogs, limiting clinical use of the
      single urine sample test.

PMID- 16426212
TI  - Detection of activated platelets in canine blood by use of flow cytometry.
AB  - OBJECTIVE: To evaluate whether markers of platelet activation, including P
      selectin expression, phosphatidylserine exposure, platelet-leukocyte aggregates,
      and microparticle formation, could be measured in nonstimulated and stimulated
      canine blood samples and develop a standardized protocol for detection of
      activated platelet markers in canine blood. SAMPLE POPULATION: Blood samples from
      10 dogs. PROCEDURE: Platelet activation was determined by flow cytometric
      measurement of platelets with P-selectin expression, platelet-leukocyte
      aggregates, platelet microparticles, and platelets with phosphatidylserine
      exposure. Changes in specific markers of platelet activation in nonstimulated
      versus stimulated samples were assessed by use of varying concentrations of 2
      platelet agonists, platelet-activating factor (PAF) and adenosine diphosphate.
      Flow cytometry was used to detect platelet CD61 (glycoprotein IIIa), CD62P (P
      selectin), and the leukocyte marker CD45. Annexin V was used to identify exposed
      phosphatidylserine. RESULTS: A significant difference was detected in the
      percentages of platelets with P-selectin, plateletleukocyte aggregates,
      microparticles, and platelets with annexin V exposure (phosphatidylserine) in
      samples stimulated with 10nM PAF versus the nonstimulated samples, with platelet
      leukocyte aggregates having the greatest difference. CONCLUSIONS AND CLINICAL
      RELEVANCE: Platelet activation is essential for thrombus formation and hemostasis
      and may be potentially useful for evaluation of dogs with suspected
      thromboembolic disease. Prior to development of a thrombotic state, a
      prothrombotic state may exist in which only a small number of platelets is
      activated. Identification of a prothrombotic state by use of activated platelets
      may help direct medical intervention to prevent a thromboembolic episode.

PMID- 16426213
TI  - Effects of femur position on radiographic assessment of completeness of femoral
      head and neck excision in medium- to large-breed dogs.
AB  - OBJECTIVE: To determine the effect of femur positioning on radiographic
      assessment of completeness of excision after femoral head and neck excision
      (FHNE) in medium to large breed dogs. SAMPLE POPULATION: 10 femurs from canine
      cadavers (body weight > 20 kg). PROCEDURE: Complete FHNE was performed on 5
      canine femurs. Excision consisting of inadequate removal of the medial distal
      aspect of the femoral neck was performed on the remaining 5 femurs. Each femur
      was positioned with predetermined amounts of internal and external rotation about
      the long axis and radiographed. Investigators evaluated a set of 8 radiographic
      views of each femur. Sensitivity (SE), specificity (SP), positive predictive
      value, negative predictive value, and completeness of excision assessment
      accuracy were estimated for each of the femur positions. RESULTS: Craniocaudal
      radiographic views of the femur positioned with external rotation of 15 degrees,
      30 degrees, and 45 degrees as a group had the highest SE, SP, and completeness of
      excision assessment accuracy relative to other radiographic views. The SE, SP,
      and accuracy of assessment were higher when the degree of external rotation was
      increased from 15 degrees to 30 degrees or 45 degrees. CONCLUSIONS AND CLINICAL
      RELEVANCE: Craniocaudal radiographic views of the femur positioned in external
      rotation (15 degrees, 30 degrees, and 45 degrees) improved the ability to detect
      adequacy of excision relative to standard craniocaudal and lateromedial
      radiographic views. Evaluation of craniocaudal radiographic views of the femur
      positioned in external rotation may increase the ability to assess FHNE adequacy
      in medium- to large-breed dogs.

PMID- 16426215
TI  - Measurement of urinary 11-dehydro-thromboxane B2 excretion in dogs with gastric
      dilatation-volvulus.
AB  - OBJECTIVE: To measure 11-dehydro-thromboxane B2 (11-dTXB2) in urine of healthy
      control dogs, dogs undergoing ovariohysterectomy, and dogs with gastric
      dilatation-volvulus (GDV) and assess the relationship between urinary 11-dTXB2
      concentrations in dogs with GDV and postoperative outcomes. SAMPLE POPULATION:
      Urine samples from 15 nonsurgical control dogs, 12 surgical control dogs, and 32
      dogs with GVD. PROCEDURE: Urine samples were obtained from healthy pet dogs (ie,
      nonsurgical control dogs), dogs undergoing ovariohysterectomy at anesthetic
      induction and 1 hour following surgery (ie, surgical control dogs), and dogs with
      GDV at hospital admission and 1 hour following surgical derotation of the stomach
      (ie, GDV dogs). Urinary 11-dTXB2 concentrations were determined with an ELISA and
      normalized to urinary creatinine (Cr) concentrations by calculation of the 11
      dTXB2 -to-Cr ratio. Differences in median 11-dTXB2 -to-Cr ratios among dogs and
      before and after surgery were analyzed. RESULTS: Urinary 11-dTXB2-to-Cr ratios
      did not differ between nonsurgical control dogs and surgical control dogs before
      or after surgery. Urinary 11-dTXB2-to-Cr ratios were significantly higher in GDV
      dogs at the time of hospital admission and 1 hour after surgery, compared with
      those of nonsurgical control dogs. Postoperative urine samples from GDV dogs had
      significantly higher 11-dTXB2-to-Cr ratios than postoperative urine samples from
      surgical control dogs. Median urinary 11-dTXB2-to-Cr ratios increased
      significantly in GDV dogs that developed postoperative complications. CONCLUSIONS
      AND CLINICAL RELEVANCE: Urinary 11-dTXB2 concentration is increased in GDV dogs
      at the time of hospital admission and after surgical derotation of the stomach,
      compared with that of healthy dogs. An increased urinary 11-dTXB2-to-Cr ratio
      following surgery is associated with an increased incidence of postoperative
      complications in dogs with GDV.

PMID- 16426214
TI  - Comparison of ultrasonographic characteristics of the thyroid gland in healthy
      small-, medium-, and large-breed dogs.
AB  - OBJECTIVE: To determine ultrasonographic characteristics of the thyroid gland in
      healthy small-, medium-, and large-breed dogs and evaluate the relationships of
      thyroid gland size and volume with body weight and body surface area (BSA).
      ANIMALS: 72 dogs of small (6 Toy and 6 Miniature Poodles), medium (12 Beagles),
      and large breeds (12 Akitas and 36 Golden Retrievers). PROCEDURE: Each dog's
      thyroid gland was examined ultrasonographically with a 10- to 5-MHz
      multifrequency linear-array transducer. Size, shape, echogenicity, and
      homogeneity of thyroid lobes were evaluated on longitudinal and transverse
      images. Thyroid lobe volume was estimated by use of the equation for an ellipsoid
      (pi/6 [length x height x width]). RESULTS: Thyroid lobes appeared fusiform or
      elliptical on longitudinal images and triangular or round to oval on transverse
      images. In most dogs, thyroid lobes were hyperechoic or isoechoic, compared with
      surrounding musculature, and had a homogeneous echogenic pattern. Mean length,
      width, height, and volume of thyroid lobes were significantly greater in Akitas
      and Golden Retrievers, compared with findings in Beagles or Poodles; mean length,
      width, and height were significantly greater in Beagles, compared with findings
      in Poodles. Total thyroid gland volume correlated with body weight (r = 0.73) and
      BSA (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE: Among the dog breeds examined
      ultrasonographically, thyroid lobe size and volume were more variable than shape,
      echogenicity, and homogeneity. The correlation of thyroid gland volume with BSA
      suggests that size of the dog, rather than breed, should be considered when
      assessing thyroid glands ultrasonographically.

PMID- 16426216
TI  - Serum lipase activities and pancreatic lipase immunoreactivity concentrations in
      dogs with exocrine pancreatic insufficiency.
AB  - OBJECTIVE: To determine serum lipase activities and pancreatic lipase
      immunoreactivity (PLI) concentrations in dogs with exocrine pancreatic
      insufficiency (EPI). ANIMALS: 74 healthy dogs and 25 dogs with EPI. PROCEDURES: A
      diagnosis of EPI was made on the basis of clinical signs, low serum trypsin like
      immunoreactivity (TLI) concentration, and response to treatment with enzyme
      replacement. Median values for fasting serum lipase activity and serum PLI
      concentrations were compared between the 2 groups with a Mann-Whitney U test.
      RESULTS: Median fasting serum lipase activity was not significantly different
      between dogs with EPI (366.0 U/L) and healthy dogs (294.5 U/L), and only 1 dog
      with EPI had a serum lipase activity less than the lower limit of the reference
      range. Median serum PLI concentration was significantly lower in dogs with EPI
      (0.1 microg/L) than in healthy dogs (16.3 microg/L). All dogs with EPI had serum
      PLI concentrations less than the lower limit of the reference range. CONCLUSION
      AND CLINICAL RELEVANCE: Serum lipase activity is not limited to the exocrine
      pancreas in origin, whereas serum PLI is derived only from the exocrine pancreas.
      Unlike in serum TLI concentrations, there was a small degree of overlap in serum
      PLI concentrations between healthy dogs and dogs with EPI. Serum TLI
      concentration remains the test of choice for diagnosis of EPI.

PMID- 16426217
TI  - In vivo measurement of flatulence and nutrient digestibility in dogs fed poultry
      by-product meal, conventional soybean meal, and low-oligosaccharide low-phytate
      soybean meal.
AB  - OBJECTIVE: To determine an optimal window for determining peak flatulence and
      evaluate the effects of oligosaccharides and supplemental beta-mannanase in
      soybean meal-based diets on nutrient availability and flatulence. ANIMALS: 6
      dogs. PROCEDURES: Dogs were used in a 2 x 3 factorial arrangement of treatments
      in a 6 x 6 Latin square experiment to evaluate the digestibility, flatulence, and
      fecal odor metabolites of low-oligosaccharide low-phytate soybean meal (LLM),
      conventional soybean meal (SBM), and poultry by-product (PBP) meal diets with or
      without supplemental beta-mannanase (5 g/kg). RESULTS: Enzyme supplementation had
      no effect on total tract dry matter (DM), nitrogen digestibility, or digestible
      energy; however, differences between protein sources did exist for total tract DM
      digestibility and digestible energy. The PBP meal had higher DM digestibility and
      digestible energy (mean, 0.913 and 4,255 cal/g), compared with soy-based diets
      (mean, 0.870 and 4,049 cal/g). No differences were detected for any treatment
      regardless of protein source or addition of supplemental enzyme for any
      flatulence components analyzed. No differences were detected for all fecal odor
      metabolites regardless of addition of supplemental enzyme; however, differences
      between protein sources were detected. The PBP meal had lower concentrations of
      carboxylic acids and esters and higher concentrations of heterocycles, phenols,
      thio and sulfides, ketones, alcohols, and indoles than LLM and SBM. CONCLUSIONS
      AND CLINICAL RELEVANCE: Diets containing < 22.4 g of stachyose/kg and < 2 g of
      raffinose/kg did not alter digestibility or increase flatulence in dogs.

PMID- 16426218
TI  - Distribution of mRNA coding for 5-hydroxytryptamine receptor subtypes in the
      intestines of healthy dairy cows and dairy cows with cecal dilatation
      dislocation.
AB  - OBJECTIVE: To investigate the distribution of mRNA coding for 7 subtypes of 5
      hydroxytryptamine receptors (5-HTRs) in the intestines of healthy dairy cows and
      dairy cows with cecal dilatation-dislocation (CDD). SAMPLE POPULATION: Full
      thickness intestinal wall biopsy specimens were obtained from the ileum, cecum,
      proximal loop of the ascending colon, and external loop of the spiral colon
      (ELSC) of 15 cows with CDD (group 1) and 15 healthy dairy cows allocated to 2
      control groups (specimens collected during routine laparotomy [group 2] or after
      cows were slaughtered [group 3]). PROCEDURE: Amounts of mRNA coding for 7
      subtypes of 5-HTRs (5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, and 5-HT4)
      were measured by quantitative real-time reverse transcriptase-PCR assay. Results
      were expressed as the percentage of mRNA expression of a housekeeping gene.
      RESULTS: Expression of mRNA coding for 5-HTR1B, 5-HTR2B, and 5-HTR4 was
      significantly lower in cows with CDD than in healthy cows. For 5-HTR2B and 5
      HTR4, significant differences between cows with CDD and control cows were most
      pronounced for the ELSC. Expression of mRNA for 5-HTR1D, 5-HTR1F, and 5-HTR2A was
      extremely low in all groups, and mRNA for 5-HTR1A was not detected. CONCLUSIONS
      AND CLINICAL RELEVANCE: Relative concentrations of mRNA coding for 5-HTR1B, 5
      HT2B, and 5-HTR4 were significantly lower in the intestines of cows with CDD than
      in the intestines of healthy dairy cows, especially for 5-HT2B and 5-HTR4 in the
      ELSC. This supports the hypothesis that serotonergic mechanisms, primarily in the
      spiral colon, are implicated in the pathogenesis of CDD.

PMID- 16426219
TI  - Identification of case clusters and counties with high infective connectivity in
      the 2001 epidemic of foot-and-mouth disease in Uruguay.
AB  - OBJECTIVE: To evaluate the influence of individual spatial units (ie, counties)
      on the epidemic spread of foot-and-mouth disease (FMD) virus. SAMPLE POPULATION:
      163 counties in Uruguay where there was an outbreak of FMD between April 23 and
      July 11, 2001. PROCEDURE: A geographically referenced database was created, and
      the distance between counties (13,203 county pairs), road density of counties
      (163 counties), and time when cases were reported in those counties (11 weeks of
      the epidemic) were considered to assess global spatial and spatial-temporal
      autocorrelation, determine the contribution of links connecting pairs of counties
      with infected animals, and allow us to hypothesize the influence for spread
      during the epidemic for counties with greater than the mean infective link
      contributions. RESULTS: Case clusters were indicated by the Moran Iand Mantel
      tests during the first 6 weeks of the epidemic. Spatial lags between pairs of
      counties with infected animals revealed case clustering before and after
      vaccination was implemented. Temporal lags predicted autocorrelation for up to 3
      weeks. Link indices identified counties expected to facilitate epidemic spread.
      If control measures had been implemented in counties with a high index link
      (identifiable as early as week 1 of the epidemic), they could have prevented (by
      week 11 of the epidemic) at least 2.5 times as many cases per square kilometer
      than the same measures implemented in counties with average link indices.
      CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of spatial autocorrelation and
      infective link indices may identify network conditions that facilitate (or
      prevent) disease spread.

PMID- 16426220
TI  - Prevalence of vesivirus in a laboratory-based set of serum samples obtained from
      dairy and beef cattle.
AB  - OBJECTIVE: To examine sera obtained from dairy and beef cattle to detect
      antibodies against vesivirus and compare seroprevalence among cattle within the
      sample population. SAMPLE POPULATION: Cattle sera from 8 western states and
      Maryland submitted to the Washington Animal Disease Diagnostic Laboratory during
      1999 and 2000. PROCEDURE: Sera were analyzed for vesivirus-specific antibodies by
      use of a recombinant vesivirus-San Miguel sea lion virus serotype 5-capsid
      peptide antigen in an indirect ELISA. RESULTS: Overall, 693 sera were tested and
      105 (15.2%) had positive results. Seropositive cattle were from 7 states (all
      cattle from Montana and Maryland 10 and 4, respectively were seronegative).
      Overall seroprevalence for antivesivirus antibody in herds ranged between 0% and
      80% (median, 14%). Higher antibody prevalence was significantly associated with
      older age, dairy rather than beef cattle, and reasons for submission. Logistic
      regression of factors (abortion, respiratory tract disease, and all other reasons
      for sample submission) revealed that older age and other reasons were
      independently associated with higher seroprevalence. Higher seropositive optical
      density values for the ELISA were observed among older cattle and cattle that
      aborted, compared with values for cattle with respiratory tract disease or other
      reasons for submission. CONCLUSIONS AND CLINICAL RELEVANCE: This laboratory-based
      surveillance sample provided a point estimate of seroprevalence against vesivirus
      among cattle in 9 US states. This suggests that vesivirus infection is widespread
      with high prevalence in some herds. Risk factors associated with vesivirus
      seroprevalence in beef and dairy cattle should be confirmed in population-based
      studies.

PMID- 16426222
TI  - Expression of the PTEN tumor suppressor gene in malignant mammary gland tumors of
      dogs.
AB  - OBJECTIVE: To determine whether changes in expression level of the phosphatase
      and tensin homolog deleted on the chromosome 10 (PTEN) gene are associated with
      malignant transformation in mammary gland tumors in dogs. SAMPLE POPULATION:
      Specimens of 5 benign and 8 malignant mammary gland tumors and 2 unaffected
      mammary glands from dogs. PROCEDURE: The open reading frame (ORF) sequence of
      PTEN gene in each specimen was analyzed via a direct-sequencing method;
      expression levels of PTEN gene were quantified via a competitive reverse
      transcription (RT)-PCR method. RESULTS: Compared with findings in clinically
      normal samples, amounts of PTEN mRNA were increased 2- to 4-fold in 4 of the 5
      benign mammary gland tumor samples. In contrast, PTEN expression was remarkably
      low in 4 of the 8 malignant tumor samples (approx 12% to 37% of the level in
      unaffected mammary gland specimens). Gene amplification via the RT-PCR method
      with total RNA prepared from malignant tumor samples as a template yielded 3
      bands that were smaller than the full-length ORF product of PTEN gene; in 2 of
      those 3 RT-PCR products, exons 6 and 7 or exons 3 to 8 were absent. No mutation
      was detected in the full-length ORF product of PTEN gene. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that a decreased level of PTEN gene
      expression (compared with unaffected mammary gland tissue) is associated with
      malignancy in canine mammary tumors. Analysis of PTENgene expression level in
      dogs with mammary gland tumors may provide useful prognostic information.

PMID- 16426221
TI  - Evaluation of the risk of motor neuron disease in horses fed a diet low in
      vitamin E and high in copper and iron.
AB  - OBJECTIVE: To determine whether equine motor neuron disease (EMND) could be
      induced in adult horses fed a diet low in vitamin E and high in copper and iron.
      ANIMALS: 59 healthy adult horses. PROCEDURE: Horses in the experimental group (n
      = 8) were confined to a dirt lot and fed a concentrate low in vitamin E and high
      in iron and copper in addition to free-choice grass hay that had been stored for
      1 year. Control horses (n = 51) were fed a concentrate containing National
      Research Council-recommended amounts of copper, iron, and vitamin E. The hay fed
      to control horses was the same as that fed to experimental horses, but it had not
      been subjected to prolonged storage. Control horses had seasonal access to
      pasture, whereas experimental horses had no access to pasture. Horses that
      developed clinical signs of EMND were euthanatized along with an age-matched
      control horse to determine differences in hepatic concentrations of vitamin E,
      vitamin A, copper, iron, and selenium. RESULTS: 4 experimental horses developed
      clinical signs of EMND. Plasma concentrations of vitamin E decreased in all 8
      experimental horses. There were no significant changes in plasma concentrations
      of vitamin A, selenium, and copper or serum concentrations of ferritin. There
      were no significant differences in those analytes between experimental horses
      with EMND and experimental horses that did not develop EMND. No control horses
      developed EMND. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that lack of
      access to pasture, dietary deficiency of vitamin E, or excessive dietary copper
      are likely risk factors for EMND.

PMID- 16426223
TI  - Comparison of the use of new handheld tonometers and established applanation
      tonometers in dogs.
AB  - OBJECTIVE: To examine the practical aspects, accuracy, and reproducibility of 2
      new automatic handheld tonometers in dogs and compare them with results for 2
      established applanation tonometers. ANIMALS: 15 freshly enucleated canine eyes
      for manometric evaluation and 20 conscious research dogs, 20 client-owned dogs,
      and 12 dogs with acute glaucoma for clinical tonometry. PROCEDURE: Calibration
      curves were determined for all 4 tonometers on 15 enucleated canine eyes.
      Intraocular pressure (IOP) was measured with each tonometer consecutively in
      conscious dogs, with the MacKay-Marg applanation tonometer as the reference
      device. Measurements were repeated in 20 sedated dogs. An induction-impact
      tonometer was evaluated clinically on dogs with acute glaucoma. Additionally,
      measurements obtained by an experienced and an inexperienced examiner and with or
      without use of topical anesthesia were compared. RESULTS: The portable
      pneumatonometer was cumbersome and time-consuming. Compared with results for the
      reference applanation tonometer, and confirmed by manometry, the portable
      pneumatonometer increasingly underestimated actual IOP values with increasing
      IOP. The induction-impact tonometer provided accurate and reproducible
      measurement values. There was a significant strong correlation between the IOP
      values obtained by the 2 examiners (r2, 0.82) and also with or without topical
      anesthesia (r2, 0.86). In dogs with glaucoma, the fitted line comparing values
      for the reference applanation tonometer and induction-impact tonometer closely
      resembled an ideal 1:1 relationship. CONCLUSIONS AND CLINICAL RELEVANCE: Use of
      the portable pneumatonometer in dogs appears to have disadvantages. The induction
      impact tonometer appears to provide a promising alternative to the use of
      applanation tonometers in dogs.

PMID- 16426225
TI  - Effects of an alveolar recruitment maneuver on cardiovascular and respiratory
      parameters during total intravenous anesthesia in ponies.
AB  - OBJECTIVE: To evaluate pulmonary and cardiovascular effects of a recruitment
      maneuver (RM) combined with positive end-expiratory pressure (PEEP) during total
      intravenous anesthesia in ponies. ANIMALS: 6 healthy adult Shetland ponies.
      PROCEDURE: After premedication with detomidine (10 microg/kg, IV), anesthesia was
      induced with climazolam (0.06 mg/kg, IV) and ketamine (2.2 mg/kg, IV) and
      maintained with a constant rate infusion of detomidine (0.024 mg/kg/h),
      climazolam (0.036 mg/kg/h), and ketamine (2.4 mg/kg/h). The RM was preceded by an
      incremental PEEP titration and followed by a decremental PEEP titration, both at
      a constant airway pressure difference (deltaP) of 20 cm H2O. The RM consisted of
      a stepwise increase in deltaP by 25, 30, and 35 cm H2O obtained by increasing
      peak inspiratory pressure (PIP) to 45, 50, and 55 cm H2O, while maintaining PEEP
      at 20 cm H2O. Hemodynamic and pulmonary variables were analyzed at every step of
      the PEEP titration-RM. RESULTS: During the PEEP titration-RM, there was a
      significant increase in PaO 2 (+12%), dynamic compliance (+ 62%), and heart rate
      (+17%) and a decrease in shunt (-19%) and mean arterial blood pressure (-21%) was
      recorded. Cardiac output remained stable. CONCLUSIONS AND CLINICAL RELEVANCE:
      Although baseline oxygenation was high, Pa(O2) and dynamic compliance further
      increased during the RM. Despite the use of high PIP and PEEP and a high tidal
      volume, limited cardiovascular compromise was detected. A PEEP titration-RM may
      be used to improve oxygenation in anesthetized ponies. During stable hemodynamic
      conditions, PEEP titration-RM can be performed with acceptable adverse
      cardiovascular effects.

PMID- 16426224
TI  - Evaluation of the effects of dietary n-3 fatty acid supplementation on the
      pharmacokinetics of doxorubicin in dogs with lymphoma.
AB  - OBJECTIVE: To determine the effect of dietary n-3 fatty acids on the
      pharmacokinetics of doxorubicin in dogs with lymphoma. ANIMALS: 23 dogs with
      lymphoma in stages IIIa, IVa, and Va. PROCEDURE: Dogs receiving doxorubicin
      chemotherapy were randomly allocated to receive food with a high (test group) or
      low (control group) content of n-3 fatty acids. Serum doxorubicin and
      doxorubicinol concentrations were measured via high-performance liquid
      chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node
      concentrations of doxorubicin were assessed 6 hours after the initial treatment.
      Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry
      scans. RESULTS: No significant differences in doxorubicin pharmacokinetics were
      detected between treatment groups. Significant differences existed between the
      first and second sampling times among all dogs for area under the curve, maximum
      serum concentration, and clearance. Differences in body composition did not
      affect measured pharmacokinetic variables. The terminal elimination half-life was
      longer in dogs in which a long-term remission was achieved than in dogs that did
      not have remission. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation
      of n-3 fatty acids is common in veterinary patients with neoplasia, but
      supplementation did not affect doxorubicin pharmacokinetics in this population of
      dogs. Explanations for the beneficial effects of n-3 fatty acids other than
      alterations in the pharmacokinetics of chemotherapy drugs should be investigated.
      Dogs may metabolize drugs differently prior to remission of lymphoma than when in
      remission. The pharmacokinetics of doxorubicin at the time of the first
      administration may predict response to treatment.

PMID- 16426226
TI  - Cellular composition of bronchial brushings obtained from healthy dogs and dogs
      with chronic cough and cytologic composition of bronchoalveolar lavage fluid
      obtained from dogs with chronic cough.
AB  - OBJECTIVE: To determine whether bronchial brushings from dogs with chronic cough
      have increased numbers of goblet cells and WBCs, compared with numbers for
      healthy dogs, or have differing WBC populations, compared with populations in
      bronchoalveolar lavage (BAL) fluid obtained from dogs with chronic cough.
      ANIMALS: 9 healthy dogs and 10 dogs with chronic cough. PROCEDURE: Specimens were
      collected by use of bronchoscopy. Cellular composition was determined for
      brushings, and results from dogs with chronic cough were compared with those from
      healthy dogs. Cellular composition of brushings was compared with composition of
      BAL obtained from dogs with chronic cough. RESULTS: Brushings from healthy dogs
      contained a median of 2.9 x 10(6) epithelial cells, comprising 100% epithelial
      cells (96% ciliated, 3% goblet, and 1% other) and no WBCs. Brushings from dogs
      with chronic cough had 4.5 x 10(6) epithelial cells, comprising 93% epithelial
      cells (86% ciliated, 2% goblet, and 12% other). Dogs with chronic cough had
      significantly greater percentages of WBCs (7%) and neutrophils (6%), compared
      with values for healthy dogs. Five dogs with chronic cough had no neutrophilic
      inflammation evident in BAL, but 4 of these had evidence of neutrophilic
      inflammation in brushings. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophils, but
      not goblet cells, were increased in brushings from dogs with chronic cough.
      Analysis of bronchial brushings provides information about airway inflammation
      that differs from that found by examination of BAL in some dogs with chronic
      cough and is a more sensitive indicator of airway inflammation than cytologic
      examination of BAL in these dogs.

PMID- 16426227
TI  - Comparison of mesenteric lymphadenography performed via surgical and laparoscopic
      approaches in dogs.
AB  - OBJECTIVE: To determine whether injection of a mesenteric lymph node with
      iodinated aqueous contrast medium results in radiographic delineation of the
      thoracic duct and its branches, ascertain the ideal interval between injection
      and radiographic imaging, and evaluate mesenteric lymphadenography performed via
      laparoscopic and surgical approaches in dogs. ANIMALS: 10 adult dogs. PROCEDURE:
      In each dog, a right paracostal laparotomy or a right laparoscopic approach was
      performed to identify a mesenteric lymph node for injection of an iodinated
      aqueous contrast agent (0.22 mL/kg [81.4 mg of iodine/kg]). Lateral radiographic
      views were obtained at 60, 120, 180, 240, and 300 seconds after injection.
      RESULTS: A mesenteric lymph node was identified and injected with contrast medium
      in each dog. Via paracostal laparotomy, lymph node injection resulted in
      successful lymphangiographic evaluation in 4 of 5 dogs, whereas via the
      laparoscopic approach, lymph node injection resulted in successful lymphangio
      graphic evaluation in 2 of 5 dogs. In successful radiographic evaluations,
      injected lymph nodes, mesenteric lymphatics, and the thoracic duct and its
      branches were delineated. Radiographs obtained at 60 and 120 seconds after
      injection of contrast medium provided the most detail. CONCLUSIONS AND CLINICAL
      RELEVANCE: Injection of a mesenteric lymph node directly with contrast medium
      appears to be a feasible technique for delineation of the thoracic duct and its
      branches in dogs and might be useful in small animals in which mesenteric
      lymphatic catheterization can be difficult and lymphangiography is more likely to
      fail. Refinement of the laparoscopic technique may provide a minimally invasive
      approach to lymphadenography.

PMID- 16426228
TI  - Use of a jugular vein graft in a modified Blalock-Taussig procedure in dogs.
AB  - OBJECTIVE: To determine whether autologous jugular veins provide functional
      grafts with high 30-day patency rates in an experimental model of systemic-to
      pulmonary shunting performed with a modified Blalock-Taussig procedure. ANIMALS:
      15 healthy Beagles. PROCEDURE: A segment of the left jugular vein was implanted
      between the left subclavian and pulmonary arteries. Echocardiograms were obtained
      prior to surgery, at day 4 to 7, and at day 30 after surgery. Selective
      angiograms were performed immediately after surgery and on day 30. Oximetric
      shunt calculations were made via terminal angiography prior to euthanasia. Gross
      and histologic evaluations of the grafts were conducted. RESULTS: Grafts were
      patent in 12 of 15 dogs 30 days after surgery as assessed via auscultation, color
      Doppler ultrasonography, angiography, and histologic examination.
      Echocardiographic analysis revealed compensatory eccentric left ventricular
      hypertrophy. Mean pulmonary-to-systemic flow ratio was 1.5:1. Histologic evidence
      of endothelialization of the anastomotic sites and vein graft arterialization was
      detectable at 30 days. CONCLUSIONS AND CLINICAL RELEVANCE: Autologous jugular
      vein grafts were effectively used to create a systemic-to-pulmonary shunt by use
      of a modified Blalock-Taussig procedure. High patency, ready accessibility, low
      cost, and theoretical adaptative remodeling during patient growth make autologous
      jugular vein grafts a valuable alternative to synthetic materials.

PMID- 16426229
TI  - Ghrelin, an endogenous growth hormone secretagogue with diverse endocrine and
      nonendocrine effects.

PMID- 16426230
TI  - Single-case experimental designs in veterinary research.

PMID- 16426231
TI  - Characterization of yeast pyruvate kinase 1 as a protein kinase A substrate, and
      specificity of the phosphorylation site sequence in the whole protein.
AB  - Pyk1 (pyruvate kinase 1) from Saccharomyces cerevisiae was characterized as a
      substrate for PKA (protein kinase A) from bovine heart and yeast. By designing
      Pyk1 synthetic peptides containing potential PKA sequence targets (Ser22, Thr94
      and Thr478) we determined that the peptide S22 was a substrate for PKA in vitro,
      with a K(sp)* (specificity constant) 10-fold and 3-fold higher than Kemptide for
      bovine heart and yeast PKA respectively. In vitro phosphorylation of the Pyk1
      S22A mutant protein was decreased by as much as 90% when compared with wild-type
      Pyk1 and the Pyk1 T94A mutant. The K(sp)* values for Pyk1 and Pyk1 T94A were the
      same, indicating that both proteins are phosphorylated at the same site by PKA.
      Two-dimensional PAGE of Pyk1 and Pyk1 S22A indicates that in vivo the S22A
      mutation prevented the formation of one of the Pyk1 isoforms. We conclude that in
      yeast the major PKA phosphorylation site of Pyk1 is Ser22. Phosphorylation of
      Ser22 leads to a Pyk1 enzyme that is more active in the absence of FBP (fructose
      1,6-bisphosphate). The specificity of yeast and mammalian PKA towards the S22
      peptide and towards whole Pyk1 protein was measured and compared. The K(sp)* for
      the S22 peptide is higher than that for Pyk1, indicating that the peptide
      modelled on Pyk1 is a much better substrate than Pyk1, regardless of which tissue
      was used as the source of PKA. However, the K(m) of Pyk1 protein is lower than
      that of the better substrate, the S22 peptide, indicating that ground-state
      substrate binding is not the major determinant of substrate specificity for PKA.

PMID- 16426234
TI  - Ethics of international clinical research collaboration - the experience of
      AlloStem.
AB  - This paper examines the ethics of international clinical collaboration in stem
      cell research by focusing on the AlloStem project. AlloStem is an international
      research programme, financed by the European Union under the Sixth Framework
      Programme, with the aim of advancing the use of stem cells in treating leukaemia
      and other haematological diseases. Several areas of ethical importance are
      explored. Research justification and the need to consider both deontological and
      teleological aspects are examined. Ethical sensitivity in research and the
      requirement to respond to areas of ethical concern identified by the European
      Commission, such as the involvement of human beings, the use of human tissue, and
      the use of animals are also explored. Ethical issues around project structure and
      management, such as ethical standardization in international research, and
      achieving set targets are discussed. The ethical importance of dissemination of
      findings and teaching in clinical research is also considered. Finally, the
      distribution of benefits is addressed and the importance of distributive justice
      is emphasized.

PMID- 16426232
TI  - Yeast Hsl7 (histone synthetic lethal 7) catalyses the in vitro formation of omega
      N(G)-monomethylarginine in calf thymus histone H2A.
AB  - The HSL7 (histone synthetic lethal 7) gene in the yeast Saccharomyces cerevisiae
      encodes a protein with close sequence similarity to the mammalian PRMT5 protein,
      a member of the class of protein arginine methyltransferases that catalyses the
      formation of omega-N(G)-monomethylarginine and symmetric omega-N(G),N'(G)
      dimethylarginine residues in a number of methyl-accepting species. A full-length
      HSL7 construct was expressed as a FLAG-tagged protein in Saccharomyces
      cerevisiae. We found that FLAG-tagged Hsl7 effectively catalyses the transfer of
      methyl groups from S-adenosyl-[methyl-3H]-L-methionine to calf thymus histone
      H2A. When the acid-hydrolysed radiolabelled protein products were separated by
      high-resolution cation-exchange chromatography, we were able to detect one
      tritiated species that co-migrated with an omega-N(G)-monomethylarginine
      standard. No radioactivity was observed that co-migrated with either the
      asymmetric or symmetric dimethylated derivatives. In control experiments, no
      methylation of histone H2A was found with two mutant constructs of Hsl7.
      Surprisingly, FLAG-Hsl7 does not appear to effectively catalyse the in vitro
      methylation of a GST (glutathione S-transferase)-GAR [glycine- and arginine-rich
      human fibrillarin-(1-148) peptide] fusion protein or bovine brain myelin basic
      protein, both good methyl-accepting substrates for the human homologue PRMT5.
      Additionally, FLAG-Hsl7 demonstrates no activity on purified calf thymus histones
      H1, H2B, H3 or H4. GST-Rmt1, the GST-fusion protein of the major yeast protein
      arginine methyltransferase, was also found to methylate calf thymus histone H2A.
      Although we detected Rmt1-dependent arginine methylation in vivo in purified
      yeast histones H2A, H2B, H3 and H4, we found no evidence for Hsl7-dependent
      methylation of endogenous yeast histones. The physiological substrates of the
      Hsl7 enzyme remain to be identified.

PMID- 16426233
TI  - Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene.
AB  - The Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) transcription factor
      regulates gene expression of the GCLC (glutamate-cysteine ligase catalytic
      subunit), which is a key enzyme in glutathione synthesis, and GSTs (glutathione S
      transferases) via the ARE (antioxidant-response element). The Mrp2 (multidrug
      resistance protein 2) pump mediates the excretion of GSH and GSSG excretion as
      well as endo- and xeno-biotics that are conjugated with GSH, glucuronate or
      sulphate. Considering that Mrp2 acts synergistically with these enzymes, we
      hypothesized that the regulation of Mrp2 gene expression is also dependent on
      Nrf2. Using BHA (butylated hydroxyanisole), which is a classical activator of the
      ARE-Nrf2 pathway, we observed an increase in the transcriptional activity of
      Mrp2, GCLC and Gsta1/Gsta2 genes in the mouse liver. A similar pattern of co
      induction of Mrp2 and GCLC genes was also observed in mouse (Hepa 1-6) and human
      (HepG2) hepatoma cells treated with BHA, beta-NF (beta-naphthoflavone), 2,4,5-T
      (trichlorophenoxyacetic acid) or 2AAF (2-acetylaminofluorene), suggesting that
      these genes share common mechanism(s) of transcriptional activation in response
      to exposure to xenobiotics. To define the mechanism of Mrp2 gene induction, the
      5'-flanking region of the mouse Mrp2 gene (2.0 kb) was isolated, and two ARE-like
      sequences were found: ARE-2 (-1391 to -1381) and ARE-1 (-95 to -85). Deletion
      analyses demonstrated that the proximal region (-185 to +99) contains the
      elements for the basal expression and xenobiotic-mediated induction of the Mrp2
      gene. Gel-shift and supershift assays indicated that Nrf2-protein complexes bind
      ARE sequences of the Mrp2 promoter, preferentially to the ARE-1 sequence.
      Overexpression of Nrf2 increased ARE-1-mediated CAT (chloramphenicol
      acetyltransferase) gene activity, while overexpression of mutant Nrf2 protein
      repressed the activity. Thus Nrf2 appears to regulate Mrp2 gene expression via an
      ARE element located at the proximal region of its promoter in response to
      exposure to xenobiotics.

PMID- 16426235
TI  - Association study of polymorphisms in SOCS family genes with type 1 diabetes
      mellitus.
AB  - Suppressors of cytokine signalling (SOCS) proteins play important roles in the
      negative regulation of cytokine signal. We first searched for polymorphisms in
      SOCS-1, SOCS-3 and SOCS-5 genes, and examined the association of the
      polymorphisms with type 1 diabetes (T1D). As a result, we did not find any
      significant associations between SOCS genes and T1D.

PMID- 16426236
TI  - Global distribution of a novel trinucleotide microsatellite polymorphism (ATA)n
      in intron 8 of the SLC11A1 gene and susceptibility to pulmonary tuberculosis.
AB  - We identified a novel trinucleotide (ATA)n repeat polymorphism in intron 8 of
      SLC11AI, a candidate gene for susceptibility to tuberculosis (TB) infection. We
      characterized the frequency of this polymorphism in 485 individuals originating
      from eight globally diverse human populations and compared the distribution of
      (ATA)n alleles in 146 adults and in 80 cord blood samples from newborns in the
      Gambian population. Lastly, we tested for association of this microsatellite with
      pulmonary TB in 318 TB cases and 146 controls in the Gambian population. We found
      no significant difference in frequency or distribution of alleles in adult and
      cord blood samples, and we found no significant association between this marker
      and pulmonary TB.

PMID- 16426237
TI  - Erythrocyte complement receptor 1 (CR1) expression level is not associated with
      polymorphisms in the promoter or 3' untranslated regions of the CR1 gene.
AB  - Complement receptor 1 (CR1) expression level on erythrocytes is genetically
      determined and is associated with high (H) and low (L) expression alleles
      identified by a HindIII restriction fragment-length polymorphism (RFLP) in intron
      27 of the CR1 gene. The L allele confers protection against severe malaria in
      Papua New Guinea, probably because erythrocytes with low CR1 expression, are less
      able to form pathogenic rosettes with Plasmodium falciparum-infected
      erythrocytes. Despite the biological importance of erythrocyte CR1, the genetic
      mutation controlling CR1 expression level remains unknown. We investigated the
      possibility that mutations in the upstream or 3' untranslated regions of the CR1
      gene could control erythrocyte CR1 level. We identified several novel
      polymorphisms; however, the mutations did not segregate with erythrocyte CR1
      expression level or the H and L alleles. Therefore, high and low erythrocyte CR1
      levels cannot be explained by polymorphisms in transcriptional control elements
      in the upstream or 3' untranslated regions of the CR1 gene.

PMID- 16426238
TI  - Lack of association between the TNF-alpha promoter gene polymorphism and
      susceptibility to B-cell chronic lymphocytic leukaemia.
AB  - B-cell chronic lymphocytic leukaemia (B-CLL) is a lymphoproliferative disorder
      characterized by clonal expansion of B lymphocytes. The present study aimed to
      determine whether there is an association between the polymorphic features
      located within the promoter/enhancer region of tumour necrosis factor-alpha
      (TNFA) gene and susceptibility to B-CLL. TNFA (-308 G/A) promoter single
      nucleotide polymorphism (SNP) was determined by polymerase chain reaction with
      sequence-specific primers (PCR-SSP) using commercial oligonucleotides. No
      significant association was found between the distribution of TNFA alleles and B
      CLL in Polish patients with B-CLL. Our single centre results were compared with
      other literature data and combined in a cumulative analysis employing the Mantel
      Haenszel method. Among 183 B-CLL patients, 47 (26%) were carrying TNFA*2 allele
      and this allele was present in 98 out of 348 controls (28%). Also, the results of
      the Mantel-Haenszel test did not show a significant correlation [Mantel-Haenszel
      estimate of approximate relative risk (RMH) = 0.86, P = 0.294]. These results
      suggest that TNFA (-308) alleles are not involved in the predisposition to the
      development of B-CLL.

PMID- 16426239
TI  - Evidence for linkage and association between autoimmune thyroid diseases and the
      18q12-q21 region in a large Tunisian family.
AB  - Many studies have shown linkage between IDDM6 locus on 18q12-q21 chromosome and
      several autoimmune diseases, suggesting that it might harbour susceptibility
      genes common to autoimmunity. Using 12 families deriving from a large Tunisian
      multiplex family (the Akr family) from which 38 people were affected with
      autoimmune thyroid diseases (AITD), and 193 unrelated AITD patients, tested
      against 100 healthy subjects, we tried to replicate the positive results
      previously reported for the IDDM6. Akr members were genotyped with eight
      microsatellite markers harbouring the IDDM6 region. Multipoint non-parametric
      linkage analysis have shown a clear peak values of NPL score around D18S41 marker
      (Z = 3.72, P = 0.0001). Family-based association test (FBAT) and transmission
      disequilibrium test (TDT) have confirmed linkage results. In particular, a
      significant association with allele 3 of D18S41 and allele 2 of D18S57 markers
      was found. Case-control studies, using one intragenic microsatellite (locus
      CTG18.1) marker in the immunoglobulin transcription factor (ITF2) gene, a 5'
      flanking AC repeat of the anti-apoptotic BCL-2 gene as well as two SNPs at
      positions +52 and +1955 from transcription start site of BCL-2, showed no
      significant association between neither genes and AITD. Our study is the first
      replication of the 18q12-q21 chromosome region as a potential candidate to AITD
      genetic susceptibility. The Akr family has shown evidence for linkage between
      IDDM6 locus and AITD. Moreover, case-control study does not support the
      involvement of ITF2 and BCL2 genes in AITD pathogenesis.

PMID- 16426240
TI  - Characterization of a novel DRB1*14 allele (DRB1*1449) in the Han-Chinese
      population.
AB  - We report here a novel human leukocyte antigen (HLA) allele, DRB1*1449, in the
      Han-Chinese population. The nature of the new allele was confirmed by the
      sequencing-based typing (SBT) method. Genomic DNA and six subclones containing
      DNA fragment of DRB1 exon 2 were sequenced in both forward and reverse
      directions. The exon 2 nucleotide sequence of DRB1*1449 is closely related to
      DRB1*1432 allele based on sequence homology. It has four nucleotide (nt)
      substitutions at positions 71, 196, 244 and 245 in exon 2, which lead to changes
      of amino acid sequences. The serological assignment of DRB1*1449 is DR14 based on
      the serological HLA typing result. This novel allele might be a result of
      recombination between DRB1*1402 and DRB1*140101 like alleles, which are very
      common among Chinese population.

PMID- 16426241
TI  - Polymorphism of HLA-DRB1 gene shows no strong association with ulcerative colitis
      in Chinese patients.
AB  - The genetic factors predisposing to ulcerative colitis (UC) have remained totally
      unclear to date. This study aimed to investigate the role of HLA-DRB1 genetic
      polymorphism in the susceptibility to develop UC in Chinese patients. HLA-DRB1
      genotyping was carried out in 72 unrelated patients with UC and 314 healthy
      controls by using polymerase chain reaction-sequence-specific primers (PCR-SSP).
      All of the patients and healthy controls are Han people in China. The frequency
      of DRB1*07 allele was increased in UC patients compared with healthy controls
      (19.4% vs. 9.2%, P = 0.0229, OR = 2.372, 95%CI: 1.181-4.766), but the
      significance disappeared when given Bonferroni correction (P(C) = 0.2977).
      Furthermore, compared with healthy controls, although HLA-DRB1*07,
      DRB1*16/DRB1*09 and DRB1*07/DRB1*12 genotypes were increased in frequency in the
      patients with extensive colitis, and the patients without extraintestinal
      manifestations (EIMs) carried an increased frequency of HLA-DRB1*07 and
      DRB1*07/DRB1*12 genotypes, these differences did not reach statistical
      significance after Bonferroni correction. HLA-DRB1 alleles showed no strong
      association with UC, and no HLA-DRB1 alleles or genotypes were strongly
      associated with clinical subgroups of UC in Chinese patients.

PMID- 16426242
TI  - The role of HLA molecules in susceptibility to chronic rheumatic heart disease.
AB  - Only a small fraction of the streptococcal pharyngitis progress to rheumatic
      carditis, which implies that environmental, host and microbial factors interact
      to cause an aberrant immune response against the antigens of the microorganism
      that cross-react with cardiac tissues. Although there are numerous studies and a
      general consensus on the relation between human leucocyte antigen (HLA) class II
      antigens and rheumatic heart disease (RHD), the details and the culprit antigens
      are still controversial. The study was undertaken to examine 100 patients with
      chronic RHD and 100 controls for HLA class I and class II antigens for
      differences in prevalence. All samples were typed at the HLA-DRB1/3/4/5 and DQB1
      loci by the sequence-specific primer (PCR-SSP) method at low resolution. For HLA
      class I antigens, HLA-B13 frequency was marginally increased in patients with RHD
      compared to controls without reaching statistical significance. For class II
      antigens, RHD patients had higher frequencies for HLA-DRB1*01 (RHD 24%, controls
      10%), DRB1*04 (RHD 35%, controls 26%), DRB1*07 (RHD 18%, controls 11%) and HLA
      DQB1*02 (RHD 32%, controls 17%) without reaching statistical significance, and
      significantly lower frequencies for DRB1*13 (Pc < 0.003, OR: 5.69), DRB5* (Pc <
      0.003, OR: 33) and DRB3* (Pc = 0.03, OR: 2.66) compared to controls. It was
      concluded that host, microbial and environmental factors collude to create acute
      rheumatic fever (RF) and chronic rheumatic valve disease. The HLA-DRB1*13, DRB5*
      and DRB3* were protective against the development of rheumatic valve damage.

PMID- 16426243
TI  - CCR2 allele polymorphisms in 15 Chinese ethnic populations.
AB  - Chemokine receptor-2 (CCR2) is a co-receptor for the entry of human
      immunodeficiency virus-1 (HIV-1) into the target cells. A mutation in CCR2 (CCR2
      64I) exhibited a protective effect to delay the progression of acquired
      immunodeficiency syndrome (AIDS). To study the mutant frequency and polymorphism
      of CCR2 in Chinese populations, 1082 individuals from 15 Chinese populations
      distributing widely from north to south were collected. The genotypes of CCR2-64I
      were determined by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) with the digestion of restriction endonuclease FokI. Of
      the 1082 individuals, 352 (32.53%) were carriers of CCR2-64I allele, 257 of whom
      (23.75%) were heterozygotes (CCR2-64V/I), whereas 95 (8.78%) were homozygotes
      (CCR2-64V/V). The frequency of the CCR2-64I allele in those tested individuals
      was 20.66%. This prevalence of CCR2-64I was higher than what was known for
      American and European populations. Moreover, the frequencies of CCR2-64I were
      generally higher in northern China than they were in southern China, and the
      frequencies had significant variance in 15 populations of China (chi2 = 27.135, P
      = 0.018).

PMID- 16426244
TI  - Association between ICAM-1 Gly-Arg polymorphism and renal parenchymal scarring
      following childhood urinary tract infection.
AB  - Renal parenchymal scarring (RPS) following urinary tract infection (UTI) is an
      important cause of renal morbidity in children. Studies have shown that the
      intensity of the inflammatory response following infection is related to the risk
      of RPS. However, genetic variability in this response has not been studied.
      Adhesion molecules play a crucial role in leucocyte recruitment following
      infection, and polymorphisms have been reported in the genes for key cell
      adhesion molecules. We have investigated the possibility that children who
      develop RPS following UTI may exhibit altered genotype or allele frequencies for
      polymorphisms of the intercellular adhesion molecule-1 (ICAM-1) (exons 4 and 6),
      E-selectin (exons 2 and 4), platelet endothelial cell adhesion molecule-1 (PECAM
      1) (exon 3) and CD11b (3'UTR) genes, which may predict outcome of UTI. DNA was
      isolated from 99 children shown to have developed RPS, 43 children with no
      evidence of scarring (NS) following UTI and 170 healthy controls. Genotyping was
      performed by restriction fragment length polymorphism (RFLP) analysis. When the
      RPS group was compared with the NS group, there was a significant reduction in
      the frequency of the ICAM-1 exon 4 A allele (10.6 vs. 21.3%, respectively, chi2 =
      6.01, P = 0.014). There was no significant difference in either allele or
      genotype frequency for any of the other polymorphisms studied. These data suggest
      that the A allele of the ICAM-1 exon 4 polymorphism may protect against the risk
      of RPS following UTI and may participate in the regulation of the inflammatory
      response following UTI.

PMID- 16426245
TI  - HLA-G polymorphism in a Chinese Han population with recurrent spontaneous
      abortion.
AB  - Reproduction is an important biological phenomenon posing an immunological
      paradox because the semiallogeneic fetus survives by evading maternal immune
      recognition. The detailed mechanisms behind this maternal-fetal immunotolerance
      remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I
      antigen, initially identified as a molecule selectively expressed on extravillous
      cytotrophoblasts and first studied in the context of pregnancy, has long been
      supposed to play a critical role in fetal-maternal immunotolerance. To
      investigate the role of HLA-G polymorphism in this process and whether the HLA-G
      genotype is associated with an increased risk for a subsequent miscarriage, 69
      women with three or more recurrent spontaneous abortions (RSA) and 146 fertile
      control women were genotyped for the HLA-G locus in this study. To our knowledge,
      this is the first report on HLA-G polymorphism in RSA and in normal fertile women
      from a Chinese Han population. Nine HLA-G alleles were detected in the fertile
      control group; however, the allele HLA-G*0103 was absent in the RSA group. No
      statistical significance was observed in the distribution of HLA-G alleles
      between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA
      group and in normal fertile women is 0.7% and 1.4%, respectively. Our data
      suggested that there was no association of HLA-G polymorphism with RSA.

PMID- 16426246
TI  - Promoter polymorphism rs3087456 in the MHC class II transactivator gene is not
      associated with susceptibility for selected autoimmune diseases in German patient
      groups.
AB  - We analysed whether the single nucleotide polymorphism (SNP) rs3087456 in the
      promoter of the MHC class II transactivator (MHC2TA) gene is associated with
      manifestation of rheumatoid arthritis, multiple sclerosis, narcolepsy and Wegener
      granulomatosis. The recently reported association in a northern population of the
      MHC2TA variation with these autoimmune diseases is not evident in the German
      population.

PMID- 16426247
TI  - Nomenclature for factors of the HLA system, October 2005 update*.

PMID- 16426248
TI  - Atopy, eczema and breast milk fatty acids in a high-risk cohort of children
      followed from birth to 5 yr.
AB  - BACKGROUND: The incidence of atopic diseases such as eczema is increasing in
      westernized societies. The suggestion that there is a "protective" association
      between the unique fatty acid composition of breast milk, particularly the omega
      3 (n-3) and omega-6 (n-6) essential polyunsaturated fatty acid content, and the
      development of atopic disease in children was investigated in a cohort study of
      263 infants born into families with a history of allergy (one or both parents had
      asthma, hayfever, eczema). The objectives of this study were to determine the
      lipid profile [specifically in relation to long-chain polyunsaturated fatty acid
      (LC-PUFA) composition] in maternal breast milk samples collected at 6 wk and at 6
      months following birth, and to investigate the potential role of these fatty
      acids in modulating the phenotype of children at high genetic risk of developing
      atopic disease. METHOD: Breast milk samples were available from 91 atopic mothers
      at their child's ages of 6 wk and 6 months. These samples were analysed for the
      fatty acid spectrum. Analysis of variance was used to detect differences between
      groups of outcomes (no atopy or eczema, non-atopic eczema, atopy, atopic eczema)
      at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to
      isolate the parameters producing the different results (F-test, LSD test). For
      the exposure variables, n-3 and n-6 fatty acids are expressed as weight
      percentage and as a ratio (at both time-points). RESULTS: The fatty acid profiles
      of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of
      n-6: n-3 fatty acids in both 6 wk and 6 month milk samples was associated with
      non-atopic eczema (p < 0.005) but not atopy alone or atopic eczema. CONCLUSION:
      We found milk fatty acids were a significant modulator of non-atopic eczema but
      not atopy or atopic eczema in infants at 6 months. In mothers with a history of
      asthma, hayfever or eczema, their 6-month-old infants were more likely to develop
      non-atopic eczema if their milk had a higher ratio of n-6: n-3 LC-PUFA.

PMID- 16426249
TI  - Association between neopterin in cord blood, urinary neopterin in early childhood
      and the development of atopic dermatitis, asthma and hay fever.
AB  - It is generally accepted that the increased prevalence of atopic disease is due
      to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by
      the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release
      large amounts of neopterin. Thus, the determination of neopterin concentrations
      is an indirect measure of the levels of IFN-gamma and allows us to monitor Th1
      type immune response. We evaluated whether neopterin concentrations in the
      neonatal cord blood could be a valuable marker predicting atopic disease in early
      childhood and whether there is a difference in actually determined urinary
      neopterin concentrations in children with and without atopic disease. Five
      hundred and five children born during 1997-1999 were enrolled, with cord blood
      neopterin data available at birth. The International study of asthma and
      allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of
      wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning
      urinary samples were collected and urinary neopterin concentration was measured
      by high-pressure liquid chromatography. By the average age of 6 yr, the
      prevalence of atopic disease in the last 12 months was 31%. There was no
      significant correlation between cord blood and urinary neopterin concentrations
      at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary
      neopterin concentrations were significant lower in children with a family history
      of atopic disease (p = 0.02). In this study, cord blood neopterin concentration
      was not a predictor for atopic disease in early childhood. Family history of
      atopic disease was associated with lower urinary neopterin levels at age 6 yr,
      which might mirror a Th1/Th2 imbalance.

PMID- 16426250
TI  - Domestic allergen and endotoxin exposure and allergic sensitization in Cyprus.
AB  - We investigated the relationship between domestic allergen and endotoxin exposure
      and allergic sensitization among children in Cyprus. We skin prick tested 128
      children aged 15-16 yr (random samples of 85 children with self-reported asthma
      and 43 healthy controls) and measured their domestic exposure to endotoxin and
      allergens (mite, cat, and dog). We analyzed the data using multivariate logistic
      regression (adjusting for gender, area of residence and parental history) and
      presented the outcomes as odds ratios (OR) and 95% confidence intervals (CI).
      Among this selected population, 19% of children were sensitized to mite, 15% to
      cat and 7% to dog. Male gender (OR 2.74, 95% CI 1.18-6.38, p = 0.02), maternal
      history of allergic disease (OR 3.53, 95% CI 1.13-11.00, p = 0.03), increasing
      endotoxin (OR 1.58, 95% CI 1.00-2.49, p = 0.05) and residence in the district of
      Nicosia (OR 2.48, 95% CI 1.01-6.08, p = 0.05) were independent associates of
      allergic sensitization. Factors associated with mite sensitization were
      increasing Der p 1 and endotoxin exposure (OR 1.28, 95% CI 1.01-1.62, p = 0.04
      and OR 1.76, 95% CI 1.01-3.08, p = 0.05, respectively) and living in an urban
      area (OR 6.80, 95% CI 1.37-33.67, p = 0.02). Sensitization to domestic pets was
      associated only with paternal allergic disease (cat: OR 5.68, 95% CI 1.57-23.56,
      p = 0.02; dog: OR 13.5, 95% CI 1.79-101.73, p = 0.01), but not with pet ownership
      or specific allergen or endotoxin exposure. In conclusion, mite allergen exposure
      was associated with sensitization to mite, but there was no association between
      cat and dog allergen exposure and specific sensitizations. Surprisingly, in this
      area, increasing endotoxin exposure was associated with an increased risk of
      sensitization.

PMID- 16426251
TI  - Current cat ownership may be associated with the lower prevalence of atopic
      dermatitis, allergic rhinitis, and Japanese cedar pollinosis in schoolchildren in
      Himeji, Japan.
AB  - The aim of the study was to clarify the relationship between current pet
      ownership, passive smoking, and allergic diseases among the Japanese children.
      From 1995 to 2001, we distributed the Japanese edition of the questionnaire of
      the American Thoracic Society and the Division of Lung Diseases (ATS-DLD) to
      survey allergic diseases among 35,552 6-yr-old children at primary school in the
      city of Himeji, Japan. We analyzed the data by multiple logistic regression and
      calculated adjusted odds ratios for environmental factors, including passive
      smoking and pet (dog and/or cat) ownership. There were no significant
      relationships between the prevalence of asthma and current pet ownership and
      passive smoking. However, current cat ownership was related to a significantly
      lower prevalence of atopic dermatitis [adjusted odds ratio (aOR) 0.79, 95%
      confidence interval (CI) 0.67-0.93], allergic rhinitis (aOR: 0.71, 95% CI 0.57
      0.89) and Japanese cedar pollinosis (aOR 0.57, 95% CI 0.44-0.75). Strikingly,
      passive smoking was also related to a significantly lower prevalence of allergic
      rhinitis (aOR 0.83, 95% CI 0.77-0.89) and Japanese cedar pollinosis (aOR 0.81,
      95% CI 0.74-0.88). Current cat ownership was associated with a lower prevalence
      of atopic dermatitis, allergic rhinitis, and Japanese cedar pollinosis. In
      addition, passive smoking was also associated with a lower prevalence of allergic
      rhinitis and Japanese cedar pollinosis.

PMID- 16426252
TI  - Gender analysis in acute bronchiolitis due to respiratory syncytial virus.
AB  - It is reasonable to compare immune reactions between boys and girls because many
      infections in the early stages are predominant in males. A relationship between
      immunomodulatory effects of sex hormone surge in boys at early months and
      infectious diseases is still unclear. We compared clinical features between boys
      and girls who suffered from wheezing that was initially triggered by acute
      respiratory syncytial virus (RSV) bronchiolitis. For systemic immune response
      evaluation, white blood cell (WBC) count, blood eosinophil count, and serum C
      reactive protein (CRP) were measured. For local inflammation evaluation, scores
      for eosinophils and neutrophils in sputum were evaluated microscopically.
      Patients consisted of 90 boys and 51 girls. Most children were under 6 months of
      age. WBC counts and serum CRP levels were significantly increased in girls
      compared with boys. Blood eosinophilia at the acute stage was rarely observed in
      children after 6 months of age. For local response evaluation, sputum specimens
      obtained from 42 boys and 29 girls were microscopically examined. Sputum
      eosinophil score of 2+ and more was observed in boys (6/42) exclusively. In
      contrast, sputum neutrophilia was commonly observed in boys and girls. From a
      follow-up study, we confirmed that 28 children with RSV bronchiolitis showed
      wheezing episodes afterwards. However, their blood and sputum eosinophilia during
      RSV bronchiolitis did not reflect their subsequent wheezing. We speculated that
      gender-specific responses to RSV infection might account for male susceptibility.
      Differences in RSV pathogenicity between boys and girls should be further
      investigated in terms of asthma progression.

PMID- 16426253
TI  - Mast cell activation and leukotriene secretion in wheezing infants. Relation to
      respiratory syncytial virus and outcome.
AB  - The persistence of wheezing after early wheezing episodes in infancy may be
      related to the virus involved and to the type of inflammation during the initial
      wheezing. The role of mast cell activation and leukotriene secretion in wheezing,
      and the relation to outcome, is not known. Our objective was to study markers of
      mast cell activation and leukotriene secretion from wheezing infants, and the
      relation to respiratory syncytial virus (RSV) infection and persistent wheezing.
      Urinary 9alpha,11beta-PGF(2), a marker of mast cell activation, and urinary
      leukotriene E4 were measured in 106 infants hospitalized for wheezing during
      their first year of life. Results were related to the presence of RSV infection
      and the persistence of wheezing at follow-up 20 months later. Levels of
      9alpha,11beta-PGF(2) were higher in infants positive for RSV than in those with
      RSV negative wheezing, but both groups had higher levels than controls.
      Leukotriene E4 levels were higher in wheezing infants than in controls. Urinary
      9alpha,11beta-PGF(2) levels were higher in infants with transient compared with
      persistent wheezing. We found a positive correlation between 9alpha,11beta-PGF(2)
      and leukotriene E4, strongest in infants with RSV negative disease and in infants
      with persistent wheezing. The results suggest that mast cells play an important
      role in infant wheezing, and may be a major source of leukotriene secretion in
      these infants. Mast cell activation and leukotriene secretion were not associated
      with persistent wheezing.

PMID- 16426254
TI  - Ketotifen induced inhibition of histamine release in a non-IgE model of middle
      ear effusion.
AB  - The inhibitory effects of ketotifen, a histamine H1-receptor antagonist and mast
      cell stabilizer, were examined on a non-IgE experimental model of middle ear
      effusion. Thirty rats were divided into three groups. Group A (n = 9) was
      subjected to mechanical stimulation of the external auditory canal (EAC); group B
      (n = 11) was pre-treated with intraperitoneal administration of 0.2 mg ketotifen,
      90 min before mechanical stimulation of the EAC; and group C (n = 10), the
      control group, was neither exposed to mechanical stimulation nor given ketotifen.
      Thirty minutes after completion of the experiment, the eardrums were inspected,
      histamine levels were determined by a fluorometric assay, and the pars flaccida
      underwent histological assessment. An attic effusion was observed in group A; a
      similar phenomenon but to a lesser extent was also seen in group B. Statistical
      analysis confirmed that the mean histamine concentration of the rinsing fluid
      obtained from group A was significantly higher than that of group C (p = 0.004)
      or group B (p = 0.008). No significant difference was found between the mean
      histamine concentration of groups C and group B (p = 0.311). Histological
      assessment revealed that the thickness of the pars flaccida of group A was
      considerably greater than that of groups C and B and was characterized by marked
      edema. Furthermore, the pars flaccida mast cell population was significantly
      depleted compared with groups C and B. The data indicate that mechanical
      stimulation of the EAC triggered the pars flaccida mast cells to degranulate in a
      non-mediated IgE fashion and that histamine is implicated in most of these
      histological changes. It is concluded that administration of ketotifen before
      mechanical stimulation of the EAC had a stabilizing effect and abolished mast
      cell degranulation, therefore, may be considered as a potential therapeutic agent
      for the treatment of middle ear disease in the pediatric population.

PMID- 16426255
TI  - Randomized placebo-controlled trial comparing montelukast and cetirizine for
      treating perennial allergic rhinitis in children aged 2-6 yr.
AB  - Leukotriene receptor antagonists (LTRAs) were recently added to the method of
      treating allergic rhinitis (AR). However, in children under 6 yr old, there has
      been no study about its efficacy in treating AR. We aim to compare the clinical
      efficacy of montelukast, cetirizine and placebo in the treatment of children from
      2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any
      significant differences. Sixty children were selected and treated with
      montelukast, or cetirizine, or placebo once daily. The efficacy of the three
      agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life
      Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we
      also examined serum IgE, serum eosinophil cationic protein (ECP), blood
      eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in
      nasal smears. The results revealed that both montelukast and cetirizine were
      significantly efficacious compared with placebo in NAR, eosinophil percentage in
      nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat
      itching and tearing. For nasal itching, only cetirizine was significantly
      efficacious. On the other hand, for night sleep quality, montelukast was
      significantly superior to cetirizine.

PMID- 16426256
TI  - Patterns of latex allergen recognition in children sensitized to natural rubber
      latex.
AB  - Single recombinant latex allergens permit the study of the pattern of
      sensitization to individual allergens. We aimed to quantify the IgE-response to
      individual latex allergens in children sensitized to latex. The study group
      included 31 latex-sensitized children: 26 operated at least twice, 20 of them
      with spina bifida; two children with one operation and three atopic non-operated
      children. IgE antibodies to rHev b 1, rHev b 3, rHev b 5, rHev b 6.01, rHev b
      7.02 and rHev b 8, coupled to ImmunoCAPs, were measured in each serum. IgE
      responses to rHev b 1, rHev b 5 and rHev b 6.01 were found in 17 children each,
      and their mean +/- s.d. levels were 5 +/- 7.4, 16.8 +/- 14 and 10 +/- 18 kU/l,
      respectively. IgE responses to rHev b 3 (4 +/- 5.4 kU/l) were found in eight
      children. Two children had IgE to rHev b 7 (1.7 and 3.2 kU/l), and none to rHev b
      8. Four sera were negative to all tested recombinant allergens. We divided the
      patients in three groups: sensitized only to rHev b 1, sensitized only to rHev b
      5 and/or rHev b 6.01, and sensitized to both rHev b 1 and to rHev b 5 and/or rHev
      b 6.01. The three groups had the same profile of clinical features. Hev b 5
      induces the quantitatively higher IgE responses in children with multiple
      surgeries sensitized to latex. Responses to Hev b 6.01 equal those of Hev b 1.

PMID- 16426257
TI  - Inhibitory effect of pooled human immunoglobulin on cytokine production in
      peripheral blood mononuclear cells.
AB  - Human intravenous immunoglobulins (IVIG) are widely used as immunomodulators
      because of their ability to modify the course of various immune-mediated
      diseases. We investigated the mechanisms responsible for the regulatory effects
      of IVIG on in vitro human peripheral blood mononuclear cell (PBMC) cytokine
      production. Pre-incubation of PBMCs with IVIG inhibited lipopolysaccharide (LPS)
      and phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulated cytokine
      secretion. Pre-incubation of PBMCs with IVIG induced a significant inhibition of
      LPS-stimulated (IL-6) secretion (p = 0.045); the effect on tumor necrosis factor
      alpha (TNF-alpha) secretion was not significant (p = 0.234). Pre-incubation of
      PBMCs with IVIG inhibited IL-6 secretion (p = 0.033) stimulated with anti-CD14
      antibody cross-linking but had no significant effect on TNF-alpha secretion (p =
      0.125). PBMC pre-incubation with anti-CD14-blocking antibody induced a
      significant reduction (p = 0.042) in LPS-stimulated TNF-alpha secretion in
      comparison with a non-significant reduction (p =0.256) noted with IVIG pre
      treatment. In contrast, pre-incubation of PBMCs with anti-CD14 antibody did not
      induce a significant reduction in LPS-stimulated IL-6 secretion (p = 0.166) in
      comparison with a significant reduction (p = 0.001) induced with IVIG pre
      treatment. Our data suggest that the immunoregulatory properties of IVIG may rely
      on several mechanisms, some of which may be independent of CD14. Our data also
      showed that cross-linking cell membrane-bound IVIG with anti-human kappa- and
      lambda-chain antibodies resulted in cytokine secretion levels similar to those
      elicited by LPS. In addition, intracellular DNA staining results did not support
      the involvement of apoptosis in the regulatory mechanisms of IVIG. This data may
      further our understanding of the immunoregulatory effects exerted by IVIG on the
      production of inflammatory-response mediators.

PMID- 16426258
TI  - Case verification of children with asthma in Ontario.
AB  - Asthma is an important chronic childhood illness. A population-based surveillance
      program could measure the burden of illness, but first, the validity of an
      administrative diagnosis of asthma must be confirmed. The objective was to
      evaluate the accuracy of population-based outpatient administrative data in
      identifying children with asthma for the purpose of on-going asthma surveillance
      and research. Twenty-one primary care physician (PCP) clinics in Ontario
      participated. Patients under 18 yr old were categorized into three diagnosis
      categories according to administrative data diagnosis codes: asthma, asthma
      related, and non-asthma. In each PCP clinic, for each diagnosis category, 10
      charts were randomly selected for abstraction. A panel of experts (blind to the
      code) reviewed the abstracted charts and identified them as asthma or non-asthma.
      The reviewers' diagnosis was considered the gold standard. The accuracy of the
      administrative data diagnosis coding was analyzed using the concepts of
      diagnostic test evaluation. Six hundred and thirty patient charts were abstracted
      and reviewed. Overall agreement between the diagnosis provided by expert chart
      review and the administrative data diagnosis code was 84.8% (p < 0.001), and was
      60.2%, 94.8% and 99.5% for the asthma, asthma-related, and non-asthma categories,
      respectively. Additionally, the sensitivity and specificity were 91.4% and 82.9%,
      respectively. Agreement between the administrative data diagnosis code and the
      PCP chart diagnosis was 99.4% (p < 0.001). An administrative data diagnosis code
      of asthma is sensitive and specific for identifying asthma. By using the results
      of this study as a starting point, future research will create a cohort of
      children with asthma to be used for population-based surveillance and research.

PMID- 16426259
TI  - Amino acid variants in Surfactant protein D are not associated with bronchial
      asthma.
AB  - Surfactant protein D (SFTPD) belongs to the family of collectins and is part of
      the innate immune system. Thereby it plays an important role in the defense of
      various pathogens. Besides it is involved in the development of acute and chronic
      inflammation of the lung. Levels of SFTPD are elevated in serum and alveolar
      lavage of asthmatic patients. As SFTPD binds and neutralizes common allergens
      like house dust mites it is especially important in allergic asthma. Three common
      amino acid variants have been identified in SFTPD and association of the first
      variant has been described to severe infection with respiratory syncytial virus.
      Furthermore the functional impact of all three amino acid variants has been
      demonstrated. Due to its function SFTPD represents an ideal candidate gene for
      bronchial asthma and we were interested whether the polymorphisms were in
      association with asthma in children. The three polymorphisms leading to amino
      acid exchanges (Met11Thr, Ala160Thr, and Ser270 Thr) were typed by restriction
      fragment length polymorphisms in 322 asthmatic children and 270 controls.
      Association analyses were performed by Armitage's trend test. In addition
      haplotypes were calculated by FASTEHPLUS and FAMHAP. None of the polymorphisms
      was in association with bronchial asthma. Haplotype analyses revealed four major
      haplotypes all of which were evenly distributed between the populations. We
      conclude from our data that functional amino acid variants in SFTPD do not play a
      major role in the genetic pre-disposition to bronchial asthma in children.

PMID- 16426261
TI  - Post-marketing experience with an opioid nasal spray for migraine: lessons for
      the future.
AB  - In 1992 a nasal spray formulation of butorphanol, an opioid medication intended
      for pain relief, was marketed in the USA on an unscheduled basis. Only a few
      years later, amid widespread reports of abuse and dependence, primarily in
      migraine patients, its manufacturer voluntarily requested the Food and Drug
      Administration to reschedule the drug as a Schedule IV narcotic. The events
      surrounding this episode are reviewed, and four problem areas that might have
      contributed are identified: (i) inadequate review of previous experience with
      other formulations of butorphanol; (ii) failure to consider the impact of disease
      state and drug formulation on the risk of adverse events; (iii) the limited scope
      of clinical trials prior to approval; and (iv) aggressive marketing efforts. The
      implications of these lessons for future drug development and post-marketing
      surveillance in the migraine field are considered.

PMID- 16426262
TI  - Infrequent or non-response to oral sumatriptan does not predict response to other
      triptans--review of four trials.
AB  - A migraineur can claim to be an infrequent responder ('non-responder') to an oral
      triptan independent of which triptan he or she is presently using. Four trials of
      an alternative triptan (zolmitriptan/rizatriptan; eletriptan; naratriptan;
      almotriptan) in patients with a history of infrequent response to oral
      sumatriptan were compared and contrasted in terms of study design, patient
      characteristics, and efficacy and tolerability of the triptan under
      investigation. Unfortunately, none of the reported studies used an appropriate
      parallel design, which would have had the non-responding triptan (oral
      sumatriptan) in one arm and without encapsulation. While the four trials differed
      in terms of study design (open-label vs. placebo-controlled), definition of
      sumatriptan 'non-responder' (retrospective vs. prospective) and pain intensity at
      baseline (30% severe to 70% severe), all four demonstrated that lack of response
      to sumatriptan did not predict lack of response to an alternative triptan.
      Changing triptans resulted in 2-h pain-relief rates of 25-81% in patients with a
      history of poor response to sumatriptan. It can be concluded that migraine
      patients who respond infrequently to sumatriptan should be switched to a
      different triptan, as lack of response to one triptan does not predict likelihood
      of responsiveness to another. A review of the available evidence suggests that
      almotriptan may be one of the most appropriate choices for an alternative
      triptan.

PMID- 16426263
TI  - Behaviour during attacks and assessment of intensity in primary headaches of
      children and adolescents.
AB  - Assessment of attack intensity in primary headaches of paediatric age has not
      received great attention in the literature to date and in the international
      classification the criteria to define pain intensity are also not specified. The
      purpose of this research was to evaluate whether behaviour during attacks,
      reported by the child or a parent, can be used as a measure of attack disability,
      and so as an indirect measure of attack intensity in primary headaches of
      children and adolescents. The subjects were 320 patients aged between 3 and 14
      years (mean age 9.9 years, SD 2.6 years) affected by primary recurrent headaches
      and first seen at a headache clinic. Twelve variables taken from their history
      were considered and sequentially analysed with multiple correspondence analysis
      and cluster analysis. Five types of behaviour during attacks were identified: (i)
      the child (or the parent) is unable to answer the questions or the child has no
      limitation in activities; (ii) the child may have some activity limitation, but
      only in lively games; (iii) the child has limitations in daily life with regard
      also to quiet activities; (iv) at least during some attacks the child lies down
      with closed eyes or in the dark; (v) during each attack the child lies down with
      closed eyes or in the dark. The least important variables for the identification
      of the five behaviour types were studying at school and absence from school.
      There are some limitations in considering child's behaviour as a measure of
      attack intensity/disability; one of these is the fact that it was found to be
      related to the educational level of the mother. However, behaviour during
      attacks, reported by the child or the parent, provides useful information
      independently of child's age and, together with the score of pain, when this is
      given, it can be used as measure of attack intensity.

PMID- 16426264
TI  - Subcutaneous sumatriptan provides symptomatic relief at any pain intensity or
      time during the migraine attack.
AB  - Over the years the paradigm of treating early during the migraine attack has
      become well established in clinical practice. It is also recommended that the 5
      HT(1B/1D) agonists be administered early during the migraine attack for efficacy.
      This is because it has been proposed that most migraineurs are less responsive to
      delayed treatment, owing to the development of central sensitization of the pain
      transmission. The main objective of this prospective, cross-over study at a
      specialist clinic was to evaluate if these recommendations should also apply to
      the subcutaneous formulation of sumatriptan. Results are based on 20 adult
      International Headache Society migraineurs. Two attacks (n=40) were treated with
      6 mg subcutaneous sumatriptan as early as possible after the onset of migraine
      headache and two attacks (n=40) as late as the patients could bear. The median
      intra-individual difference between the two strategies in time from first
      occurrence of pain to injection was 5.7 h and the median intra-individual
      difference in pain intensity at the time of injection was 29 visual analogue
      units. No significant differences were found in time to freedom from pain, pain
      severity at 1 and 2 h, area under the curves from injection to pain free or in
      headache recurrence after injection. At the end of the study, most of the
      patients claimed that their medication was as effective when given early as when
      given late in the course of the attack. The discrepancy between our present
      findings and retrospective analyses of trials on oral triptans probably has more
      to do with the less disturbed pharmacokinetics early during the migraine attack
      than with central sensitization. Consequently, we recommend nonoral formulations
      of triptans, which do not necessarily have to be administered early during the
      migraine attack to provide efficacy. In conclusion, it is reassuring for
      migraineurs that it is worthwhile taking their medication in an appropriate
      formulation even if they have not been able to do so early in the course of the
      attack.

PMID- 16426265
TI  - An epidemiological study of headache in Florianopolis, Brazil.
AB  - The aim of this study was to estimate the 1-year prevalence of headache,
      migraine, tension-type headache (TTH) and chronic daily headache (CDH), and the
      degree of association of migraine with some sociodemographic characteristics of
      the population of Florianopolis, Brazil. This is a cross-sectional, door-to-door,
      population-based study. In 300 randomly selected households, 625 subjects, aged
      15-64 years, responded to a structured questionnaire. The 1-year prevalence of
      headache was 80.8%, of migraine 22.1%, of TTH 22.9%, and of CDH 6.4%. Migraine
      and CDH were significantly more prevalent in females than in males. Migraine was
      significantly associated with the following variables: low household income, low
      electricity consumption, and divorced or widowed marital status. We have shown
      high prevalences of migraine and CDH in Florianopolis, close to the higher rates
      of previous studies. There was a preponderance of migraine in females, divorced
      or widowed, with a low socioeconomic level.

PMID- 16426266
TI  - Brainstem and cervical spinal cord Fos immunoreactivity evoked by nerve growth
      factor injection into neck muscles in mice.
AB  - Although myofascial tenderness is thought to play a key role in the
      pathophysiology of tension-type headache, very few studies have addressed neck
      muscle nociception. The neuronal activation pattern following local nerve growth
      factor (NGF) administration into semispinal neck muscles in anaesthetized mice
      was investigated using Fos protein immunohistochemistry. In order to
      differentiate between the effects of NGF administration on c-fos expression and
      the effects of surgical preparation, needle insertion and intramuscular
      injection, the experiments were conducted in three groups. In the sham group
      (n=7) cannula needles were only inserted without any injection. In the saline
      (n=7) and NGF groups (n=7) 0.9% physiological saline solution or 0.8 microm NGF
      solution were injected in both muscles, respectively. In comparison with sham and
      saline conditions, NGF administration induced significantly stronger Fos
      immunoreactivity in the mesencephalic periaqueductal grey (PAG), the medullary
      lateral reticular nucleus (LRN), and superficial layers I and II of cervical
      spinal dorsal horns C1, C2 and C3. This activation pattern corresponds very well
      to central nervous system processing of deep noxious input. A knowledge of the
      central anatomical representation of neck muscle pain is an essential
      prerequisite for the investigation of neck muscle nociception in order to develop
      a future model of tension-type headache.

PMID- 16426267
TI  - Peripheral levels of BDNF and NGF in primary headaches.
AB  - Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth
      factor (NGF), have been implicated in the generation and modulation of pain. To
      investigate whether alterations in neurotrophin levels can be detected in
      subjects suffering from nociceptive disorders, such as primary headaches, we
      determined the peripheral (platelet and plasma) levels of BDNF and NGF in
      patients suffering from migraine, with or without aura, or cluster headache (CH),
      in the interictal phase, and in healthy volunteers. All primary headaches
      patients studied showed significantly decreased platelet levels of BDNF (migraine
      vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of
      platelet NGF was observed in migraine sufferers and not in CH patients compared
      with control subjects (migraine vs. controls P<0.001). These changes were not
      accompanied by significant modifications of neurotrophin plasma levels. Our
      findings show for the first time that changes in peripheral levels of
      neurotrophines (BDNF and NGF) occur in patients suffering from different types of
      primary headaches, suggesting a potential involvement of BDNF and NGF in the
      pathophysiology of these disorders, and raising the possibility that differences
      in peripheral neurotrophins may help to distinguish migraine biologically from
      CH.

PMID- 16426268
TI  - Induction of long-lasting changes of visual cortex excitability by five daily
      sessions of repetitive transcranial magnetic stimulation (rTMS) in healthy
      volunteers and migraine patients.
AB  - We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive
      transcranial magnetic stimulation (rTMS) over the visual cortex induces
      dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in
      migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a
      normal habituation for 9 min. In the present study, we investigated whether
      repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5
      consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz
      rTMS-induced dishabituation increased in duration over consecutive sessions and
      persisted between several hours (n=4) and several weeks (n=4) after the fifth
      session. In six out eight migraineurs, the normalization of VEP habituation by 10
      Hz rTMS lasted longer after each daily stimulation but did not exceed several
      hours after the last session, except in two patients, where it persisted for 2
      days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical
      excitability and VEP habituation pattern. Whether this effect may be useful in
      preventative migraine therapy remains to be determined.

PMID- 16426269
TI  - Factors determining headache at onset of acute ischemic stroke.
AB  - Headache is a frequent accompaniment of acute ischaemic stroke. The predisposing
      factors and underlying mechanisms are currently incompletely defined. We analysed
      prospectively collected data relevant to headache occurring at ischaemic stroke
      onset in consecutive patients included in the Henry Ford Hospital Stroke Data
      Bank. Patients with headache (HA+) and without headache (HA-) were compared for
      demographic factors, medical history, medications, examination findings,
      laboratory findings, and stroke localization and subtype. Group comparisons for
      categorical data were performed with chi(2) test, and for continuous variables
      with two-sample t-tests. Stepwise logistic regression analysis, including all
      variables with P<0.25, was used to define the independent predictors of onset
      headache. Three hundred and seventy-five patients had complete headache and
      clinical datasets and were included in the analysis (HA+, N=118; HA-, N=257).
      Multivariate analysis revealed that the independent predictors of HA+ were:
      infarct in the distribution of the posterior circulation [P=0.0076, odds ratio
      (OR) 2.15, 95% confidence interval (CI) 1.23, 3.77], absence of history of
      hypertension (P=0.0106, OR 0.48, 95% CI 0.27, 0.84), and treatment with warfarin
      at the time of the index stroke (P=0.0135, OR 4.89, 95% CI 1.39, 17.21). The
      occurrence of headache at onset of ischaemic stroke is determined by posterior
      circulation distribution of the ischaemic event, absence of history of
      hypertension and treatment with warfarin at the time of the index stroke. These
      results suggest that preserved elasticity and maintenance of the intracranial
      vasculature in a relaxed state, in combination with coagulation system
      derangements, and activation of dense perivascular afferent nerves, play a role
      in the pathogenesis of onset headache.

PMID- 16426270
TI  - Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and
      association study.
AB  - Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL). Exons 3 and 4 are
      mutation hotspots. Migraine is a clinical hallmark of CADASIL. The objective of
      this study was to investigate whether genetic variants in exons 3 and 4 of the
      NOTCH3 gene are associated with migraine. Exons 3 and 4 of the NOTCH3 were
      analysed for mutations and polymorphisms by direct DNA sequencing in 97
      migraineurs and the same number of control individuals. No mutations in exons 3
      and 4 of the NOTCH3 gene were found in 97 patients with migraine. However,
      association analysis revealed significant association of the single nucleotide
      polymorphism (SNP) rs1043994 with migraine.

PMID- 16426271
TI  - Primary headaches in preschool age children: clinical study and follow-up in 163
      patients.
AB  - Although headache frequency is increasing in preschool age children, an extensive
      evaluation of the clinical features in affected patients has yet to be achieved.
      This retrospective study examined 243 patients who were separately analysed in
      two distinct groups according to the age of onset and the age of first clinical
      evaluation. Group 1 included preschool age children, while Group 2 consisted of
      pubertal age patients. In all the patients the importance of a positive family
      history for headache as a risk factor was confirmed. In addition, when compared
      with Group 2, Group 1 showed greater male gender prevalence and earlier onset of
      the attacks. Regarding clinical features, in Group 1, compared with Group 2, the
      attack duration was shorter with lower symptom association such as photo- or
      phonophobia, nausea and no pain increase during physical activity. In the same
      group, tension-type headache was the predominant diagnosis, in contrast to the
      high migraine prevalence of Group 2. This study also showed that the
      International Headache Society 1988 classification criteria are not fully
      adequate for juvenile headaches. In fact, the headaches of more than 10% of
      patients in Group 1 still remained unclassifiable, while those of all the
      subjects in Group 2 were properly classifiable.

PMID- 16426272
TI  - The relationship between migraine and atopic disorders-the contribution of
      pulmonary function tests and immunological screening.
AB  - This cross-sectional clinical study was conducted in order to explore the
      relationship between atopic disorders and migraine. We evaluated 186 consecutive
      patients with migraine. Patients with a history of atopic disorders were compared
      with the others during headache-free intervals, for their headache
      characteristics, pulmonary test (PFT) performances and immunological screenings,
      through appropriate statistical methods. Of the patients with migraine, 77
      (41.4%) reported at least one atopic disorder. PFT screening showed a general
      decreased pulmonary capacity and an important correlation between a positive
      history of atopic disorders and both increased eosinophil and IgE levels in
      headache-free periods. It should be discussed whether screening with PFT or
      immunological tests helps in early detection of progressive lung disease which
      might develop in these patients.

PMID- 16426273
TI  - Headache in Behcet's disease.
AB  - The aim of this study was to investigate the characteristics of headache in
      patients with Behcet's disease (BD) seeking neurological consultation.
      Consecutive patients with BD seen within 1 year at the neuro-Behcet's out-patient
      clinic were studied using an electronic database according to the classification
      criteria of the International Headache Society. During a 12-month period 118 BD
      patients were admitted, and 98 had headaches. Migraine was the most common type
      of primary headache diagnosed in 45 patients (46.4%) in the whole headache group,
      followed by tension-type headache (TTH) in 26 cases (26.8%). Thirty-seven
      patients had secondary headaches mainly due to cerebral venous thrombosis or
      parenchymal neurological involvement of BD. Of these patients, 15 had both
      primary and secondary headaches. The primary headaches of 13 patients were
      exacerbated with systemic BD flare-ups, and four patients had migraine attacks
      triggered only by systemic BD activation which showed a good response to the
      treatment of systemic inflammation. The majority of the headaches of patients
      with BD do not indicate any neurological involvement; they are usually due to
      migraine or TTH. In a minority of patients, migraine associated with systemic
      inflammation of BD is notable.

PMID- 16426274
TI  - Need for analgesics/drugs of abuse: a comparison between headache patients and
      addicts by the Leeds Dependence Questionnaire (LDQ).
AB  - Our aim was to compare the need for analgesics/drugs of abuse between headache
      patients--chronic and episodic headache sufferers--and addicts, by the Leeds
      Dependence Questionnaire (LDQ). This is a self-completion 10-item instrument to
      measure dependence upon a variety of substances. We administered the LDQ
      questionnaire to 122 chronic daily headache (CDH) sufferers who had been taking
      one dose of analgesic drug every day for at least 1 year; 71 subjects suffering
      from episodic headache (EH) using analgesics only occasionally; 115 consecutive
      drug addicts (DA) with a diagnosis of substance dependence. The mean LDQ total
      score was similar in the CDH (11.58+/-6.35) and DA (10.37+/-6.51) groups, and for
      both it was significantly higher than the score in the EH (5.61+/-3.00) group
      (P<0.001). The CDH group had the highest scores, and higher scores than the DA
      group (Z=-8.18, P<0.001) in item 8, assessing the primacy of effect over the kind
      of analgesic used, and in item 10 (Z=-5.03, P<0.001), asking if it is difficult
      to live without the analgesic; the DA group had the highest scores, and higher
      scores than the CDH group, in item 9 (Z=-5.07, P<0.001) addressing the need for
      the continued administration of the drug to maintain well-being, and in item 3
      (Z=-2.39, P<0.05), exploring compulsion to start the use of the drug. The EH
      group had lower scores in all items (P<0.05) except for item 9, where there was
      no difference from CDH group; the EH group had also lower scores (P<0.001) than
      the DA group, except for item 8, where, instead, the score was higher than in the
      DA group (Z=-5.33, P<0.001). A strong link develops between chronic headache
      patients and the analgesics they use. This sort of 'dependence' appears to be a
      consequence of headache, originating from the necessity for the analgesic to cope
      with everyday life.

PMID- 16426275
TI  - Behavioural and temperamental characteristics of children and adolescents
      suffering from primary headache.
AB  - To examine indices of behavioural and emotional problems and temperamental traits
      in clinically referred children and adolescents suffering from tension headache
      or migraine. Headache in childhood and adolescence (<18 years) has been
      associated with the presence of behavioural and emotional difficulties, but
      limited data are available on the relationship between these problems and
      different types of headache. Clinically referred children and adolescents
      (N=114), 6-16 years of age, suffering from primary headache according to the
      diagnostic criteria of the International Headache Society, 47 with tension-type
      headache (TH) and 67 with migraine (M), and 36 normal controls without headache
      (NC) were assessed using the Parent Child Behaviour Checklist (CBCL), Children's
      Depression Inventory (CDI), Multidimensional Anxiety Scale for Children (MASC),
      Conner's Parent Rating Scale (CPRS), and Emotionality-Activity-Sociability
      Shyness Scale (EAS). Psychological and personality self-rating assessments were
      obtained also on the children's parents and siblings. Although most headache
      patients had scores within the normative non-pathological range, both TH and M
      patients had higher CBCL total, internalizing, and externalizing scores than NC
      (P<0.001), and TH patients had higher scores than M patients. TH and M had higher
      CDI and MASC scores than NC (P<0.05), with no difference between the headache
      groups. TH patients had higher Emotionality and Shyness scores, and lower
      Sociability scores than M patients. Clinically referred children and adolescents
      with TH and M had higher scores of behavioural and emotional symptoms, both of
      internalizing and externalizing type, than normal peers. The TH group had greater
      psychological and temperamental difficulties than the M group.

PMID- 16426276
TI  - Primary headaches associated with sexual activity--some observations in Indian
      patients.
AB  - Primary headache associated with sexual activity appears to be relatively
      uncommon in a clinic-based study in Indian patients. Only 24 patients (M:F 18:6)
      were encountered over a 20-year period (1985-2004). Of the 18 male patients, 14
      (age 33-42 years) had preorgasmic headache of tension-headache type for 2-8
      months, one patient (age 58 years) had orgasmic headache of vascular type for 1
      month and three subjects (age 19-23 years) had masturbatory headache also
      simulating tension-type headache for 3-7 weeks. These observations are at
      variance with those generally reported from western countries. Of the six female
      patients, four (age 26-32 years) had typical orgasmic headache of the vascular
      type (for a few months to a few years), only one of whom had been a migraine
      sufferer. One patient (age 35 years) presented with a single episode of
      thunderclap headache where angiography had been negative. Another female subject
      (age 30 years) experienced typical orgasmic headache only during masturbation but
      not during actual sexual intercourse. Occurrence of sexual headaches in both male
      and female subjects had been unpredictable. Few had associated migraine and none
      ever experienced exertional headache.

PMID- 16426277
TI  - Right-to-left shunt and migraine: the strength of the relationship.
AB  - Several studies have shown that the prevalence of a cardial right-to-left shunt
      (RLS) in patients with migraine with aura is significantly higher than in
      patients without migraine. To assess the strength of the possible relationship
      between RLS and migraine, the literature concerning this subject was
      systematically reviewed. We identified seven relevant studies. Among patients
      with RLS migraine with aura was 3.5 times more prevalent than among subjects
      without RLS [Mantel-Haenszel odds ratio (ORMH) 3.5; 95% confidence interval (CI)
      2.1, 5.8]. In patients with ischaemic stroke migraine was more than two times
      more prevalent in patients with RLS than in patients without RLS (ORMH 2.1; 95%
      CI 1.6, 2.9). Our review shows that there is a clear association between RLS and
      migraine, especially migraine with aura. The relationship between RLS and
      migraine is further substantiated by the observations of disappearance and
      improvement of migraine symptoms after closure of the foramen ovale. However, the
      mechanism as well as the question about causality of this association has to be
      further elucidated.

PMID- 16426278
TI  - The postdrome of the acute migraine attack.
AB  - This study was performed to document the frequency, duration and types of
      symptoms of postdrome in migraine patients. Eight hundred and twenty-seven
      consecutive headache clinic patients (IHS 1.1, 1.2 and 1.5.1) were evaluated at
      first visit. Postdrome frequency, duration and characteristics were analysed.
      Sixty-eight per cent of 827 patients reported postdrome (69.1% females; 56.8%
      males, P<0.007). The average duration of the postdrome was 25.2 h. Fifty-six per
      cent had postdrome for <or=12 h, 32% for 12-24 h, 88% for <or=24 h, and 12% for
      >24 h. The commonest symptoms were tiredness (71.8%), head pain (33.1%),
      cognitive difficulties (11.7%), 'hangover' (10.7%), gastrointestinal symptoms
      (8.4%), mood change (6.8%), and weakness (6.2%). Patients with postdrome compared
      with patients without postdrome have more characteristic and more frequent
      migraine features. This study demonstrated postdrome in 68% of patients,
      duration<or=24 h in most patients, more often associated with a full-blown
      migraine attack, more common in females, and with commonest symptoms being
      tiredness and low-grade headache.

PMID- 16426279
TI  - SUNCT associated with Devic's syndrome.

PMID- 16426285
TI  - Dermatitis and aircrew.
AB  - Dermatitis is a common problem both in the workplace and in the general
      community. Airline personnel represent a novel occupational group as they are
      also exposed to a wide range of potential chemical irritants and other
      aggravating factors, such as low relative humidity and airborne pollutants.
      Common skin irritants include dielectric fluids from electrodischarge machining,
      'prepreg' materials and sealants in aircraft manufacture, kerosene and various
      jet-fuel components. Commercial jet fuel is a complex mixture of aliphatic and
      aromatic compounds, and there is potential for dermal exposure among refueling
      and maintenance crew. Low relative humidity appears to exacerbate dermatitis
      amongst aircrew, especially on longer flight durations. Pilots may also be
      exposed to additional skin irritants outside of the cabin environment, such as
      ethylene glycol, hydraulic fluid or jet fuel, all of which may be encountered
      during routine inspections of aircraft before and after flight. Given these
      factors, preventive measures must carefully consider the undoubted potential for
      contact with irritants and allergens, which may lead to dermatitis in airline
      personnel.

PMID- 16426286
TI  - An in vivo model to evaluate the efficacy of barrier creams on the level of skin
      penetration of chemicals.
AB  - The reservoir function and the barrier function are important properties of the
      skin. The reservoir function is dependent on the barrier function which, however,
      needs support by protective measures, in particular under working conditions.
      Barrier creams represent a possibility to protect the skin. In the present study,
      a method was developed to investigate the effectiveness of reservoir closure by
      different formulations. Patent Blue V in water was used as a model penetrant. Its
      penetration, with and without barrier cream treatment, was analyzed by tape
      stripping in combination with UV/VIS spectroscopic measurements. The
      investigations showed that the stratum corneum represents a reservoir for
      topically applied Patent Blue V in water. Furthermore, the barrier investigations
      showed that vaseline and bees wax form a 100% barrier on the skin surface. The
      third barrier cream, containing waxes and surfactant, only partially showed a
      protective effect against the penetration of Patent Blue V in water. Strong
      interindividual differences were observed for this barrier product. In
      conclusion, it was assumed that the application of barrier creams cannot replace
      other protective measures and should be maximally used to inhibit low-grade
      irritants or in combination with other protectants or in body areas where other
      protective measures are not applicable.

PMID- 16426287
TI  - A clinically relevant contact allergy to methyldibromo glutaronitrile at 1% (0.32
      mg/cm) detected by a patch test.
AB  - Recently, the preservative methyldibromo glutaronitrile (MDBGN) at 0.5% w/w in
      petrolatum was included in the European standard patch test series based on the
      studies on chemical stability and consideration of rates of contact allergy,
      doubtful and irritant reactions as well as information on clinical relevance
      represented by results of a repeated open application test (ROAT) and patch test
      concentrations required to diagnose allergic contact dermatitis from MDBGN in
      individual cases. In this report, a case with a clinically relevant contact
      allergy to MDBGN, which on the mandatory reading occasion on D3 only was traced
      by a patch test with MDBGN at 1.0% (0.32 mg/cm2), is presented. The patient
      suffered from a chronic hand dermatitis, and when the patient stopped using a
      liquid soap containing MDBGN, the hand dermatitis substantially improved. A ROAT
      performed in a blinded and controlled way with applications twice daily on the
      hands with 2 moisturizers with and without MDBGN resulted in a deterioration of
      the hand dermatitis on the hand to which the MDBGN-preserved moisturizer had been
      applied.

PMID- 16426288
TI  - Eczema-like plaques secondary to enoxaparin.
AB  - Low-molecular-weight heparins are used extensively in acute medicine. They are
      generally well tolerated but may cause a rare, eczema-like type IV
      hypersensitivity reaction. We report 3 cases of this eruption and speculate that
      it may be significantly under-reported due to misidentifying the causal drug,
      which may have serious consequences. We discuss treatment alternatives such as
      fondaparinux sodium, which may rarely cross-react.

PMID- 16426290
TI  - Allergenicity and cross-reactivity of naphthenic acid and its metallic salts in
      experimental animals.
AB  - The allergenicity and the cross-reactivity of naphthenic acid (NA) and its
      metallic salts were evaluated in experimental animals. In the guinea pig
      maximization test, sensitizing skin reactions were observed with cobalt
      naphthenate (CoN), zinc naphthenate (ZnN) and NA, but not with copper
      naphthenate, with CoN being the most potent sensitizer. Animals sensitized with 1
      naphthenic compound cross-reacted to the other 3 as well. Furthermore, animals in
      the CoN-sensitized group reacted to the relevant metallic salt cobalt chloride
      (CoCl2). A dose-response study using the CoN-sensitized group showed that the
      concentration of CoCl2 required to elicit a skin reaction of similar extent in
      comparison with CoN was more than 10 times higher, when skin-reaction scores were
      compared on the basis of cobalt content. In the local lymph node assay,
      significant increases in stimulation index values without skin irritation were
      observed with CoN and ZnN, where the former was more potent than the latter.
      Although CoN is a reported skin sensitizer, this study showed that skin
      allergenicity of naphthenic compounds is not restricted solely to CoN. In
      addition, the results suggest the main antigenic determinant of naphthenic
      compounds to be the structure of NA, even though metal moieties modulate their
      allergenicity.

PMID- 16426289
TI  - ROAT: morphology of ROAT on arm, neck and face in formaldehyde and diazolidinyl
      urea sensitive individuals.
AB  - The morphology of early allergic contact dermatitis reactions was studied in
      formaldehyde allergic individuals exposed to a cream product preserved with 4
      different concentrations of diazolidinyl urea. The study was made using a dose
      escalating design in 3 different anatomical regions, the upper arm, neck and
      face. On the arm and neck, the dominant initial morphology was an eczematous
      papular eruption. In the face, the initial skin changes were more homogeneous and
      infiltrated erythema.

PMID- 16426291
TI  - Can an imidazolidinyl urea-preserved corticosteroid cream be safely used in
      individuals hypersensitive to formaldehyde?
AB  - A topical corticosteroid preparation on the Swedish market, Flutivate cream,
      contains a fairly high concentration of formaldehyde (FA). In this study, we have
      investigated the clinical relevance of contact allergy to FA when treating an
      allergic eczema with Flutivate cream, containing an FA-releasing preservative. In
      a randomized, double-blind study, 7 patients hypersensitive to both FA and nickel
      repeatedly applied Flutivate cream containing FA or Betnovate cream not
      containing FA to areas of experimentally induced nickel dermatitis. 17 controls
      allergic to nickel, but not FA, went through the same procedure. In 29 per cent
      of the FA-allergic individuals, the experimental dermatitis healed when treated
      with Flutivate cream compared with 71 per cent of the controls (P = 0.04). The
      conclusion to draw from this study is that an individual hypersensitive to FA
      should not use the corticosteroid preparation Flutivate cream on dermatitis skin.

PMID- 16426292
TI  - High-fat petrolatum-based moisturizers and prevention of work-related skin
      problems in wet-work occupations.
AB  - The study presented is a randomized, controlled intervention study with the
      purpose of implementing an evidence-based skin disease prevention programme. The
      hypothesis explored in this article is whether a high-fat petrolatum-based
      moisturizer can be an alternative to protective gloves in wet-work occupations.
      The study population was all gut cleaners in Danish swine slaughterhouses, and
      data were collected by telephone interviews using a standardized questionnaire -
      The Nordic Occupational Skin Questionnaire (NOSQ-2002). At baseline, 644 (88%)
      gut cleaners responded and at 1-year follow-up 622 (72%). 135 gut cleaners in the
      intervention and 277 in the comparison group responded at both telephone
      interviews. In the intervention group, the eczema frequency was reduced
      significantly. Detailed analyses revealed that protective gloves are the overall
      most effective protective means and did not indicate that a high-fat moisturizer
      could be an alternative. Furthermore, the most extensive improvements could not
      be explained by combinations of protective behaviour but was found among those
      who had received information on, and was having discussions on prevention of skin
      problems. This only applied to the intervention group. A continuous focus on
      prevention of skin problems with information and discussions on the shop floor
      therefore seemed to be most important for reducing skin problems.

PMID- 16426293
TI  - Contact allergy and respiratory/mucosal complaints from heroin
      (diacetylmorphine).
AB  - After the start of heroin (diacetylmorphine)-assisted treatment to a selected
      group of chronic treatment-resistant heroin-dependent patients in the
      Netherlands, we reported about work-related eczema and positive patch tests to
      heroin in some nurses and nasal and respiratory complaints. To investigate the
      prevalence of heroin contact allergy, we started a questionnaire-based study with
      follow-up by allergological examinations. Of 120 questionnaires sent, 101 (84%)
      was returned: 67 from nurses and 34 from other employees. Of 101 workers, 38
      (38%) had reported work-related complaints: 33 of 67 (49%) nurses and 5 of 34
      (15%) other employees. Patch tests to heroin were performed in 24 nurses and were
      positive in 8 (33%). All the 8 had eyelid or facial eczema and, in 6, accompanied
      by mucosal or respiratory complaints. The prevalence of heroin contact allergy in
      this study was 8% (8/101) among all employees and 12% (8/67) among nurses.
      Respiratory and mucosal complaints could not be ascribed to a contact allergy,
      and in these cases, serum was analysed for specific immunoglobulin E to heroin. A
      type 1 allergy to heroin could not be shown. These complaints are possibly due to
      the histamine-liberating effect of heroin, to atopic constitution, to a
      combination of these factors or - less likely - to other non-allergic factors.

PMID- 16426294
TI  - Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea.
AB  - For several decades, the cosmetic preservatives imidazolidinyl urea (IU) and
      diazolidinyl urea (DU) have not only been poorly characterized but have also had
      misleading chemical structures assigned to them. The most common trade names of
      IU and DU are Germall 115 and Germall II, respectively. This publication gives an
      insight into what these 2 well-known contact allergens consist of and their
      degradation patterns. Approximately, 30-40% of both products can be characterized
      by mixtures of allantoin (synthetic starting material), (4-hydroxymethyl-2,5
      dioxo-imidazolidin-4-yl)-urea (compound HU) and presumably 1-(3,4-bis
      hydroxymethyl-2,5-dioxo-imidazolidin-4-yl)-1,3-bis-hydroxymethyl-urea (compound
      BHU). A full chemical characterization of compound HU is shown. The remaining
      part of both IU and DU are believed to be polymers of allantoin-formaldehyde
      condensation products. The analytical methods used to characterize IU and DU are
      capillary electrophoresis and nuclear magnetic resonance and mass spectroscopy
      studies.

PMID- 16426295
TI  - Palmar dermatitis due to a rubber escalator railing.

PMID- 16426296
TI  - Occupational allergy in office workers caused by the antifouling desk mat.

PMID- 16426297
TI  - Allergic contact dermatitis to ruscogenins.

PMID- 16426298
TI  - Glove allergy due to 1,3-diphenylguanidine.

PMID- 16426299
TI  - Isolated late asthmatic reaction after exposure to ammonium persulfate in a
      hairdresser.

PMID- 16426300
TI  - Occupational airborne contact dermatitis from pristinamycin.

PMID- 16426301
TI  - Occupational allergic contact dermatitis from hydrangea.

PMID- 16426302
TI  - Contact allergy to disperse dyes in plastic spectacle frames.

PMID- 16426303
TI  - Allergic contact dermatitis due to manganese in an aluminium alloy.

PMID- 16426304
TI  - An audit of knowledge and application of skin protective measures in hairdressers
      in Dundee.

PMID- 16426305
TI  - Occupational contact dermatitis to Mikrobac Extra in 8 hospital cleaners.

PMID- 16426306
TI  - Contact allergy to gold in patients with gold-plated intracoronary stents.

PMID- 16426307
TI  - Prediction models assessing transplant center performance: can a little knowledge
      be a dangerous thing?

PMID- 16426308
TI  - Endothelial apoptosis and chronic transplant vasculopathy: recent results, novel
      mechanisms.
AB  - Chronic transplant vasculopathy (CTV) is a progressive form of vascular
      obliteration affecting the arteries, arterioles and capillaries of solid organ
      transplants. It is characterized by intimal accumulation of mononuclear cells,
      vascular smooth muscle cells (VSMC), myofibroblasts and connective tissue.
      Mounting evidence, based on animal models and human biopsy results, suggests that
      acute and persistent rejection triggering apoptosis of endothelial cells (EC)
      plays a pivotal role in CTV. The precise mechanisms that underlie the induction
      of fibroproliferative changes in association with endothelial apoptosis have yet
      to be clearly delineated. Recent observations in the field of apoptosis research
      provide some important mechanistic clues. First, endothelial apoptosis creates a
      state of hyperadhesiveness for mononuclear cells, thus facilitating sustained
      leukocyte infiltration. Second, phosphatidylserine-dependent engulfment of
      apoptotic cells by infiltrating mononuclear leukocytes promotes transforming
      growth factor-beta1 production. Third, apoptosis of EC triggers extracellular
      matrix (ECM) proteolysis thus initiating the production of
      fibroproliferative/fibrogenic ECM fragments. The relative importance of these
      mechanisms in the pathophysiology of CTV will need to be addressed in vivo. Yet,
      these recent developments provide a new mechanistic framework that will help
      better define the importance of immune-mediated EC apoptosis in the regulation of
      vascular repair.

PMID- 16426309
TI  - The immune regulatory effect of apoptotic cells and exosomes on dendritic cells:
      its impact on transplantation.
AB  - Dendritic cells (DC) are professional antigen (Ag) presenting cells (APC) that
      trigger the anti-donor T-cell response that causes allograft rejection. During
      the past decade several laboratories have employed in vitro generated DC with
      tolerogenic potential for prolongation of allograft survival. This minireview
      describes the development of a second-generation of DC-based strategies for
      transplantation tolerance based on the delivery in situ of donor allogeneic
      (allo)-Ag to quiescent DC of graft recipients by means of donor-derived apoptotic
      cells or exosomes. Donor leukocytes in early apoptosis are rich in allo-Ag, are
      internalized efficiently by recipient DC in vivo and deliver immunosuppressive
      signals to DC. Administration (i.v.) of donor apoptotic leukocytes prolongs bone
      marrow engraftment and cardiac allografts survival in mice by exerting a profound
      down-regulatory effect on the anti-donor T-cell response. Exosomes are
      nanovesicles (<100 nm) produced by different cell types, including APC. DC
      derived exosomes are rich in major histocompatibility complex (MHC) molecules
      that can be employed to target DC in situ. Once i.v. injected, exosomes carrying
      donor MHC molecules are captured by recipient's DC and prolong allograft survival
      in rodents. The use of the regulatory functions of apoptotic cells and exosomes
      may be useful tools to develop new strategies for transplantation tolerance.

PMID- 16426310
TI  - American Society of Transplantation recommendations for screening, monitoring and
      reporting of infectious complications in immunosuppression trials in recipients
      of organ transplantation.
AB  - In recent years, major progress has been made in the development, investigation
      and clinical application of novel immunosuppressive drug therapies to prevent
      acute rejection. Critical to the ultimate clinical application of new drug
      therapies is the ongoing performance of large multi-center clinical trials.
      However, there has been a paucity of infectious disease monitoring built into
      these protocols. Given that infectious complications are a major source of
      morbidity and mortality in transplant recipients, the assessment of the magnitude
      of risk of infection associated with a given immunosuppressive strategy may be as
      important as the assessment of rejection. For the above reasons, screening,
      monitoring and reporting recommendations for common transplant-associated
      infections were developed for use in clinical trials evaluating immunosuppressive
      strategies. These recommendations have two major goals: (i) to provide clinically
      relevant definitions for tracking infectious complications occurring in
      participants in immunosuppressive trials and (ii) where appropriate, to recommend
      specific laboratory monitoring and surveillance methods.

PMID- 16426311
TI  - The Art and Science of Immunosuppression: the Fifth Annual American Society of
      Transplant Surgeon's State-of-the-Art Winter Symposium.
AB  - The 2005 American Society of Transplant Surgeons (ASTS) Winter Symposium entitled
      'The Art and Science of Immunosuppression' explored ways to maximize existing
      immunosuppressive protocols and to develop new strategies incorporating novel
      agents and emerging diagnostic technologies to customize immunosuppression and
      reduce side effects. Several presentations evaluated steroid withdrawal or
      avoidance protocols reflecting the significant difficulties of bone loss, glucose
      control and growth retardation in children associated with long-term steroid use.
      Calcineurin-inhibitor related renal dysfunction of both native and transplanted
      kidneys was identified as significant, but no consensus was reached concerning
      effective prevention. Similarly, recurrence of Hepatitis C following liver
      transplantation was identified as problematic without identifying a preferred
      immunosuppressive regimen in this setting. Control of T-cell mediated rejection
      was found to be excellent, but recognition and treatment of non-T cell causes of
      allograft damage (i.e. B- or NK-cell mediated) was identified as an area of
      current interest. Immunosuppressive agents under development, such as those
      blocking co-stimulation or cytokine signals, and JAK-3 inhibitors were discussed.
      Finally, the available technologies for molecular and genetic diagnostics and the
      clinical correlation in the post-transplant setting were discussed.

PMID- 16426312
TI  - Report of a National Conference on Donation after cardiac death.
AB  - A national conference on organ donation after cardiac death (DCD) was convened to
      expand the practice of DCD in the continuum of quality end-of-life care. This
      national conference affirmed the ethical propriety of DCD as not violating the
      dead donor rule. Further, by new developments not previously reported, the
      conference resolved controversy regarding the period of circulatory cessation
      that determines death and allows administration of pre-recovery pharmacologic
      agents, it established conditions of DCD eligibility, it presented current data
      regarding the successful transplantation of organs from DCD, it proposed a new
      framework of data reporting regarding ischemic events, it made specific
      recommendations to agencies and organizations to remove barriers to DCD, it
      brought guidance regarding organ allocation and the process of informed consent
      and it set an action plan to address media issues. When a consensual decision is
      made to withdraw life support by the attending physician and patient or by the
      attending physician and a family member or surrogate (particularly in an
      intensive care unit), a routine opportunity for DCD should be available to honor
      the deceased donor's wishes in every donor service area (DSA) of the United
      States.

PMID- 16426313
TI  - NK cells mediate costimulation blockade-resistant rejection of allogeneic stem
      cells during nonmyeloablative transplantation.
AB  - Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism
      to promote immune tolerance during murine allotransplantation, it has not yet
      been successfully translated to clinical transplantation. We determined the
      impact of natural killer (NK) cells on costimulation blockade-resistant rejection
      of donor bone marrow. We found that NK cells represent a potent barrier to
      engraftment: host NK depletion led to increased donor stem cell survival,
      increased mixed hematopoietic chimerism and to engraftment of low doses of donor
      marrow (1 x 10(8)/kg) that were otherwise rejected. To understand the mechanisms
      of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We
      found that an increased proportion of target cells were killed between days 2 and
      8 after cell transfer, and that NK killing of parental targets was inducible: NK
      cells preprimed with allotargets were more efficient at their elimination upon
      reexposure. Finally, both transplant and in vivo NK-killing models were used to
      determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led
      to decreased NK-mediated killing, and increased alloengraftment. These results
      identify NK alloreactivity as an integral component to costimulation blockade
      resistant rejection, and suggest that its inhibition may represent an important
      target in the clinical translation of tolerance-induction transplantation.

PMID- 16426314
TI  - Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in
      clinical islet transplantation.
AB  - The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical
      islet transplantation when human pancreatic islets come in contact with blood and
      may explain the initial tissue loss associated with this procedure. Low molecular
      weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use,
      inhibits both complement and coagulation activation. In a tubing loop model, LMW
      DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent
      inhibition of IBMIR with an inhibition of coagulation and complement activation
      and less consumption of platelets and other blood cells. In blood or plasma APTT
      was demonstrated to be an excellent method for monitoring the LMW-DS
      concentration both in vitro and in vivo in a nonhuman primate model. The toxicity
      was assessed using a glucose challenge test and the pharmacokinetics was tested
      in the nonhuman primate model. Here, we present a tentative protocol for using
      LMW-DS in clinical islet transplantation.

PMID- 16426315
TI  - Transplant center quality assessment using a continuously updatable, risk
      adjusted technique (CUSUM).
AB  - Access to timely, risk-adjusted measures of transplant center outcomes is crucial
      for program quality improvement. The cumulative summation technique (CUSUM) has
      been proposed as a sensitive tool to detect persistent, clinically relevant
      changes in transplant center performance over time. Scientific Registry of
      Transplant Recipients data for adult kidney and liver transplants (1/97 to 12/01)
      were examined using logistic regression models to predict risk of graft failure
      (kidney) and death (liver) at 1 year. Risk-adjusted CUSUM charts were constructed
      for each center and compared with results from the semi-annual method of the
      Organ Procurement and Transplantation Network (OPTN). Transplant centers (N =
      258) performed 59 650 kidney transplants, with a 9.2% 1-year graft failure rate.
      The CUSUM method identified centers with a period of significantly improving (N =
      92) or declining (N = 52) performance. Transplant centers (N = 114) performed 18
      277 liver transplants, with a 13.9% 1-year mortality rate. The CUSUM method
      demonstrated improving performance at 48 centers and declining performance at 24
      centers. The CUSUM technique also identified the majority of centers flagged by
      the current OPTN method (20/22 kidney and 8/11 liver). CUSUM monitoring may be a
      useful technique for quality improvement, allowing center directors to identify
      clinically important, risk-adjusted changes in transplant center outcome.

PMID- 16426316
TI  - Scoliosis after solid organ transplantation in children and adolescents.
AB  - The occurrence of scoliosis in children after solid organ transplantation is not
      known. A total of 196 children, which is 93% of patients surviving kidney, liver
      and heart transplantation in our country, participated in a cross-sectional
      survey. All children were screened for rib hump, and those with clinically
      significant hump (over 6 degrees ) underwent radiographs of the spine. The
      occurrence of scoliosis was compared to data obtained from a previously published
      comparison group. Forty-three (21.9%) of the patients had scoliosis greater than
      10 degrees , and 21 (10.7%) of them had curves greater than 20 degrees . The RR
      (95% CI) for scoliosis needing treatment (over 20 degrees ) was 17.0 (6.75-42.7)
      in the patients as compared with control population. The occurrence of scoliosis
      was 17.9% of the kidney, 13.6% of the liver and 51.7% of the heart transplant
      patients (p < 0.001). In a logistic regression model, heart transplantation (OR
      (95% CI) 7.27 (2.62-20.2)) and growth hormone treatment (3.98 (1.77-8.94)) were
      most significant risk factors for scoliosis. The risk of scoliosis is increased
      in patients with solid organ transplantation. Pediatricians treating these
      patients should be aware of this increased risk to diagnose early curves and to
      refer these patients to an orthopedic surgeon.

PMID- 16426317
TI  - Alemtuzumab induction and prednisone-free maintenance immunotherapy in
      simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte
      globulin induction - long-term results.
AB  - This study compared the effects of using two T-cell depleting antibodies,
      alemtuzumab (anti-CD 52, Campath-1H) and rabbit antithymocyte globulin
      (Thymoglobulin), as induction immunosuppression for recipients of simultaneous
      pancreas-kidney transplantation given a prednisone-free maintenance regimen. We
      used a single-center, nonrandomised, retrospective, sequential study design to
      evaluate the efficacy and safety of alemtuzumab (n = 50) or antithymocyte
      globulin (n = 38) induction in combination with a prednisone-free,
      tacrolimus/sirolimus-based immunosuppression protocol. Kaplan-Meier analyses of
      long-term patient and graft survivals and rejection rates were determined
      according to induction agent. Secondary endpoints included the quality of renal
      allograft function, incidence of infectious and malignant complications, and cost
      considerations. Overall long-term patient and graft survival rates did not
      significantly differ between patients treated with alemtuzumab and antithymocyte
      globulin. Rejection rates were also nearly equivalent at 1 and 2 years. Viral
      infectious complications were statistically significantly lower in the
      alemtuzumab group. The cost of alemtuzumab induction was lower than antithymocyte
      globulin. Alemtuzumab induction followed by steroid-free maintenance therapy with
      a tacrolimus/sirolimus-based immunosuppression regimen provided an effective,
      safe and cost-conscious approach to SPK transplantation.

PMID- 16426318
TI  - Coccidioidomycosis after renal transplantation in an endemic area.
AB  - Coccidioidomycosis is an endemic fungal infection of the desert southwestern
      United States of particular concern for immunosuppressed renal transplant
      recipients. The clinical course of coccidioidomycosis can be severe in
      immunosuppressed patients, with high rates of dissemination and mortality, and
      antifungal prophylaxis is routinely administered to high-risk patients. We sought
      to determine the impact of coccidioidomycosis on patients who received their
      renal transplant at our hospital in Phoenix, Arizona. A retrospective records
      review of the first 205 patients who received a renal transplant between June
      1999 and December 2003 identified 6 patients (3%) who had contracted
      coccidioidomycosis after transplantation. All six cases occurred more than 6
      months after transplantation. Two of these six patients had disseminated
      coccidioidomycosis. Two patients, one with pulmonary infection and one with
      disseminated infection, died. None of the six patients with coccidioidomycosis
      after transplantation had identified risk factors before transplantation. No high
      risk patient who received targeted antifungal prophylaxis had a reactivation of
      coccidioidomycosis after transplantation. Treatment for acute rejection and
      induction with antithymocyte globulin did not appear to increase the risk of
      subsequent coccidioidomycosis.

PMID- 16426319
TI  - A comparison of plasmapheresis versus high-dose IVIG desensitization in renal
      allograft recipients with high levels of donor specific alloantibody.
AB  - Several protocols allow for the successful transplantation of sensitized renal
      allograft recipients, yet no one best method has emerged. The aim of the current
      study was to compare the efficacy of high-dose IVIG with two different
      plasmapheresis (PP)-based regimens in kidney transplant recipients with high
      levels of donor specific alloantibody (DSA) defined as a positive T-cell
      cytotoxicity crossmatch. With the primary goal of achieving a negative
      crossmatch, we employed three protocols sequentially between April 2000 and May
      2005: (i) PP, low-dose IVIG, anti-CD20 antibody (n = 32); (ii) high-dose IVIG (n
      = 13); and (iii) PP, low-dose IVIG, anti-CD20 antibody and pre-transplant
      Thymoglobulin combined with post-transplant DSA monitoring (n = 16). IVIG
      decreased DSA activity in all treated patient, yet only 38% (5/13) achieved a
      negative crossmatch. In contrast, a negative crossmatch was achieved in 84% in PP
      group and 88% in the PP/monitoring group (p < 0.01 vs. IVIG). Even with a
      negative crossmatch, the rejection rates were 80% (IVIG), 37% (PP) and 29%
      (PP/monitoring), respectively, (p < 0.05 IVIG vs. PP). We conclude that multiple
      PP treatments leads to more reproducible desensitization and lower humoral
      rejection rates than a single high-dose of IVIG, but that no regimen was
      completely effective in preventing humoral rejection.

PMID- 16426320
TI  - Late ureteral stenosis following renal transplantation: risk factors and impact
      on patient and graft survival.
AB  - The aim of this retrospective study of a cohort of 1787 consecutive kidney
      transplantations was to analyze the risk factors associated with the occurrence
      of ureteral stenosis and the impact of ureteral stenosis on graft and patient
      survival. Between January 1990 and December 2002, 1787 renal transplantations
      were performed at our center. Only stenosis observed after the first month, were
      considered. Among the parameters studied were: donor age and serum creatinine
      before procurement; recipient age, cold ischemia time, delayed graft function
      (DGF), number of arteries and the presence of a double J stent. The follow-up
      parameters were the number and timing of acute rejection episodes,
      cytomegalovirus (CMV) infection, acute pyelonephritis, renal function and death.
      Ureteral stenosis occurred in 4.1% of patients and was correlated with donor age
      > 65 years (p = 0.001), kidneys with more than 2 arteries (p = 0.009) and DGF (p
      = 0.016). Ureteral stenosis did not affect 10-year patient and graft survival
      rates, which were respectively 90% and 64% for the stenosis group, 86% and 63%
      for the no-stenosis group (p = NS). These data suggest an important role for
      donor age, number of renal arteries and DGF for the occurrence of ureteral
      stenosis following renal transplantation.

PMID- 16426321
TI  - Obesity and outcome following renal transplantation.
AB  - Single institution series have demonstrated that obese patients have higher rates
      of wound infection and delayed graft function (DGF), but similar rates of graft
      survival. We used UNOS data to determine whether obesity affects outcome
      following renal transplantation. From the UNOS database, we identified patients
      who underwent primary kidney-only transplantation between 1997 and 1999.
      Recipient and donor body mass index (BMI) was categorized as underweight (BMI <
      18.5), normal (BMI 18.5-24.9), overweight (BMI 25-29.9), obese (BMI 30-34.9) or
      morbidly obese (BMI > or = 35). We correlated BMI with intermediate measures of
      graft outcome and overall graft survival, and created multivariate models to
      evaluate the independent effect of BMI on graft outcome, adjusting for factors
      known to affect graft success. The study sample comprised 27,377 recipients.
      Older age, female sex, African American race and increased comorbidity were
      associated with obesity (p < 0.001). Compared with normal weight patients, morbid
      obesity was independently associated with an increased risk of DGF (p < 0.001),
      prolonged hospitalization (p < 0.001), acute rejection (p = 0.006) and decreased
      overall graft survival (p = 0.001). Donor BMI did not affect overall graft
      survival (p > or = 0.07). Recipient obesity is associated with an increased risk
      of DGF and decreased graft survival following renal transplantation.

PMID- 16426322
TI  - The predictive value of renal vascular resistance for late renal allograft loss.
AB  - The renal artery resistance index (RI), assessed by Doppler ultrasonography, was
      recently identified as a new risk marker for late renal allograft loss. This
      finding requires confirmation since RI in that study was not measured at
      predetermined time points and ultrasonography is operator-dependent. We
      investigated the predictive value of renal vascular resistance (RVR), a less
      operator-dependent method as assessed by mean arterial pressure divided by renal
      blood flow, for the prediction of recipient mortality and death-censored graft
      loss. RVR was compared to commonly used risk markers such as creatinine clearance
      (CrCl), serum creatinine (SCreat) and proteinuria (UProt) in 793 first-time
      cadaveric renal transplant recipients at predetermined time points after
      transplantation using receiver operating characteristics (ROC) and Cox survival
      analyses. The present study showed that RVR is a prominent risk marker for
      recipient mortality and death-censored graft loss. However, the predictive value
      of RVR for recipient mortality owed mainly to the impact of mean arterial blood
      pressure. In contrast, RVR constituted more than the sum of its components for
      death-censored graft loss, but showed less predictive value than SCreat in
      univariate analysis. As the assessment of RVR is expensive and time-consuming, we
      believe that RVR holds no clinical merit for the follow-up of renal transplant
      recipients.

PMID- 16426323
TI  - Quality of life after islet transplantation.
AB  - This study analyzed quality of life in patients with type 1 diabetes that
      received islet transplantation. Twenty-three subjects were followed over 3 years.
      In addition to an interview, patients self-completed two standardized
      psychometric questionnaires, HSQ 2.0 and DQOL, before and after transplant, and
      scores were compared. Analysis was also adjusted for potential "confounders" such
      as graft dysfunction, insulin therapy and adverse events. DQOL: the Impact score
      significantly improved at all time points of the follow-up; satisfaction and
      worry scales also significantly improved at selected time points. Longitudinal
      analysis demonstrated that reintroduction of insulin had a negative effect on all
      three scales, but significant improvement in Impact scale persisted even after
      adjusting for this factor. HSQ 2.0: only the Health Perception scale
      preliminarily showed significant improvement at most time points. Longitudinal
      analysis showed loss of significance when insulin therapy was considered. Other
      scores were improved only at selected time points or not affected. Bodily pain
      scale showed deterioration at selected times. Interview: glucose control
      stability, not insulin independence, was reported as the main beneficial factor
      influencing QOL. In conclusion, islet transplantation has a positive influence on
      patients' QOL, despite chronic immunosuppression side effects. Re-introduction of
      insulin modifies QOL outcomes.

PMID- 16426324
TI  - Surgical complications and long-term outcome of different biliary reconstructions
      in liver transplantation for primary sclerosing cholangitis
      choledochoduodenostomy versus choledochojejunostomy.
AB  - Choledochojejunostomy (CJS) is commonly used for biliary reconstruction in liver
      transplantation for primary sclerosing cholangitis (PSC). We alternatively
      performed choledochoduodenostomy (CDS) and side-to-side
      choledochodocholedochstomy in a large cohort of patients. Fifty-one patients with
      PSC, transplanted between 1988 and 2000, were analyzed retrospectively. Biliary
      reconstruction was CDS in 25 (49%), CJS in 20 (39%) and CC in 6 transplantations
      (12%). Biliary leaks occurred in the early follow-up (< or =41 days) only in CDS
      patients (20%). However, in the late follow-up (>4 months), stricturing of
      anastomosis was found once in CDS (4%) and CJS (5%). Later (>9 months),
      intrahepatic bile duct strictures were diagnosed in four CDS (16%), one CJS (5%)
      and one CC (17%) patient(s). In 48% of CDS (12/25), 60% of CJS (12/20) and 17% of
      CC (1/6) at least one incidence of cholangitis was observed. Overall, biliary
      complication rates were significantly higher in CDS (40%) than CJS (10%) and CC
      (17%); of those none in CC and 12% in CDS were anastomosis-related. Graft/patient
      survival showed no significant differences among groups. Based on our results we
      consider CJS the standard method for biliary reconstruction in PSC; however, in
      selected cases where CJS is difficult to accomplish because of previous surgery
      or for retransplantation, CDS may present an alternative technique.

PMID- 16426325
TI  - Invasive fungal infections in low-risk liver transplant recipients: a multi
      center prospective observational study.
AB  - Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant
      (OLT) recipients utilizing postoperative systemic antifungal prophylaxis,
      typically with fluconazole, is justified among those at high risk for IFI. Use of
      postoperative antifungal prophylaxis for low-risk OLT recipients is widely
      practiced but not universally accepted nor supported by data. We conducted a
      prospective observational study among 200 OLT recipients who were at low risk for
      IFI and did not receive postoperative antifungal prophylaxis. Patients were
      considered low risk if they had </=1 of the following conditions:
      choledochojejunostomy anastomosis; retransplantation; intra-operative
      administration of >/=units of 40 blood products or return to the operating room
      for intra-abdominal bleeding; return to the operating room for anastomotic leak
      or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and
      perioperative Candida colonization. Patients were followed 100 d post
      transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed
      an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by
      standard fluconazole prophylaxis. Three patients developed invasive
      aspergillosis; one developed late onset disseminated cryptococcosis. Liver
      transplant recipients at low risk for IFI can be identified utilizing pre
      determined criteria, and post-transplantation antifungal prophylaxis can be
      routinely withheld in these patients.

PMID- 16426326
TI  - Liver transplantation for primary or metastatic sarcoma to the liver.
AB  - Sarcoma is generally a rare disease in the US, with poor survival in patients
      with both primary angiosarcoma and metastatic disease from sarcoma and GIST. In
      order to determine if liver transplantation for sarcoma is a realistic option, we
      examined records of all patients in the US component of the Israel Penn
      International Transplant Tumor Registry were reviewed. Those patients with liver
      failure from primary or metastatic liver sarcoma were evaluated. Patient outcome
      analysis was then performed. Patient and tumor demographics were reviewed as well
      as patient survival after transplantation. 19 patients are identified having
      received liver transplantation after treatment for sarcoma of the liver, 6
      patients with primary hepatic sarcoma and 13 patients with metastatic sarcoma of
      the liver. Recurrence was almost universal in 18 of 19 patients (95%) after a
      median interval of 6 months. Survival for the group as a whole was 47% for 1
      year, 15% for 3-years and 5% for 5-years. Given the early recurrence of tumor and
      meager 1-year survival outcome, liver transplantation is a poor therapeutic
      choice for patients with either primary or metastatic liver sarcoma, including
      high-grade leiomyosarcoma (GIST) regardless of primary site or primary therapy.

PMID- 16426328
TI  - Lung transplant recipients holding companion animals: impact on physical health
      and quality of life.
AB  - Since lung transplant recipients are susceptible to infections and inhaled
      pollution, many centers warn against pets. However, data supporting this
      recommendation are lacking. Our program is less restrictive regarding pets. This
      study, for the first time, investigates the association of pets with
      physiological and psychological parameters in these patients. A questionnaire
      concerning pets was sent to 104 lung transplant recipients. Lung function tests,
      levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and
      hospitalizations, creatinine clearance, body mass index (BMI) and demographic
      data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a
      question on summarized life satisfaction (LS), the life orientation test (LOT),
      the hospital anxiety depression scale (HADS) and the social support questionnaire
      (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined
      themselves as pet owners, whereas 48% did not. The two groups did not differ in
      demographic or physiological data. Significant differences in FLZ (79/65, p =
      0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p =
      0.04) were found in favor of pet owners. In lung transplant recipients keeping
      pets the frequency of somatic complications is not higher compared to lung
      transplant recipients without pets. After lung transplantation, pets are
      associated with a better quality of life.

PMID- 16426327
TI  - Racial and ethnic disparities in survival in lung transplant candidates with
      idiopathic pulmonary fibrosis.
AB  - Minority patients have worse outcomes than nonminority patients in a variety of
      pulmonary diseases. We aimed to compare the survival of Black and Hispanic
      patients to that of others with idiopathic pulmonary fibrosis (IPF). We performed
      a retrospective cohort study of patients with IPF who were evaluated for lung
      transplantation at our center. Kaplan-Meier survival curves and Cox proportional
      hazards models were used to compare survival between groups. Black and Hispanic
      patients had spirometry, lung volumes and diffusion capacity that were similar to
      others, but had worse exercise capacity. Minority patients had a significantly
      increased risk of death compared to others independent of transplantation status
      (hazard ratio = 3.3, 95% CI 1.2-8.9, p = 0.02). Differences in exercise capacity,
      pulmonary hemodynamics and socioeconomic factors appeared to account for some of
      the differences in survival. Black and Hispanic patients with IPF had an
      increased risk of death following referral for lung transplantation. This finding
      may be due to differences in disease progression and/or differences in access to
      medical care among minority patients. Future studies should confirm our findings
      in a larger cohort. The elimination of racial and ethnic disparities in outcome
      should be a priority for clinicians and researchers in this field.

PMID- 16426329
TI  - Calcineurin inhibitor-free immunosuppression in renal allograft recipients with
      thrombotic microangiopathy/hemolytic uremic syndrome.
AB  - Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent
      serious threats to kidney allograft recipients. During a 4-year period, among 850
      kidney transplantations, seven recipients with primary HUS and seven recipients
      (eight transplants) with previous or de novo TMA/HUS were identified and given
      calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL),
      mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were
      successful in the long term; resulting in a mean creatinine of 101 mumol/L (16.4
      months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS
      recurrences were observed. A high rate of acute rejections (53%) may indicate
      insufficient immunosuppressive power and/or a causative relationship between
      TMA/HUS and rejection. Wound-related complications were abundant (60%), and call
      for surgical/immunosuppressive countermeasures. Our experience supports the idea
      that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems
      essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of
      TMA/HUS should be carefully explored in recurrent 'high responders'.

PMID- 16426330
TI  - Postrenal transplant non-EBV multiple myeloma of donor origin.
AB  - Multiple myeloma occurring after solid organ transplantation is a rare condition,
      with only a few case reports found in the literature. We report a case of Epstein
      Barr virus-negative, posttransplant multiple myeloma in a 67-year-old female,
      presenting 18 months after renal transplantation. Interestingly, fluorescence in
      situ hybridization analysis of the tumor revealed a Y chromosome in the majority
      of the cells, indicating that the neoplasm was derived from the donor kidney. To
      our knowledge, this represents the first reported case with these features.

PMID- 16426331
TI  - Antibody-mediated rejection of a pancreas allograft.
AB  - The role of antibody-mediated rejection (AMR) in pancreas transplantation is
      poorly understood. Here, we report on a patient who developed AMR of his pancreas
      allograft after receiving a simultaneous pancreas-kidney transplant. Pre
      operative enhanced cytotoxicity and flow cytometry T-cell crossmatches were
      negative; B-cell crossmatches were not performed as per institutional protocol.
      The patient's post-operative course was significant for elevated serum amylase
      levels and development of hyperglycemia approximately 1 month after
      transplantation. A pancreatic biopsy at this time showed no cellular infiltrate
      but strong immunofluorescent staining for C4d in the interacinar capillaries.
      Analysis of the patient's serum identified donor-specific HLA-DR alloantibodies.
      He received intravenous immunoglobulin (IVIg), rituximab and plasmapheresis, and
      his pancreatic function normalized. We conclude that clinically significant AMR
      can develop in a pancreas allograft and recommend that pancreatic biopsies be
      assessed for C4d deposition if the patient has risk factors for AMR and/or the
      pathologic evidence for cell-mediated rejection is underwhelming.

PMID- 16426332
TI  - Sirolimus-associated heavy proteinuria in a renal transplant recipient: evidence
      for a tubular mechanism.
AB  - Sirolimus is a new and potent immunosuppressive agent. Recently, increased
      proteinuria has been recognized as an important complication. However, the
      mechanism thereof has remained unclear. We describe a patient who received
      sirolimus as standard therapy after living donor kidney transplantation. Within
      10 days the patient developed a severe proteinuria that disappeared completely
      after substituting tacrolimus for sirolimus. Renal biopsy disclosed normal
      glomeruli even without effacement of the podocytic foot processes. Using FITC
      labeled anti-albumin antibodies we noted complete absence of albumin in the
      proximal tubules, whereas an abundant albumin staining was observed in a control
      patient with a comparable level of proteinuria due to a recurrence of focal
      segmental glomerulosclerosis after transplantation. Our data suggest that
      sirolimus can induce severe proteinuria, and that reduced tubular protein
      reabsorption contributes to the protein loss.

PMID- 16426333
TI  - In support of list paired exchange.

PMID- 16426336
TI  - De novo HBV infection caused by an anti-HBc positive donor in a vaccinated liver
      transplant recipient in spite of anti-HBs response.

PMID- 16426340
TI  - Midterm results of off-pump coronary artery bypass surgery in 136 patients: an
      angiographic control study.
AB  - BACKGROUND: Off-pump coronary artery bypass surgery may provide an alternative
      form of surgical revascularization by avoiding the complications of
      cardiopulmonary bypass (CPB). This study summarizes the midterm results of 136
      off-pump bypass surgery patients. METHODS: Between January 2000 and March 2002,
      out of 178 surgical myocardial revascularizations, 136 (76.4%) were off-pump
      bypass surgery. Complete revascularization was done and especially arterial
      grafts were used. All patients were followed clinically and with treadmill test
      for 2 years. Average control angiography was performed at the end of 2-year
      follow-up. RESULTS: Of all the patients, 56.7% were male and the mean age of the
      patients was 63.6 +/- 7.4 years. A total of 481 anastomoses were performed-136
      (28.27%) to the left anterior descending artery (LAD), 135 (28.07%) to the
      circumflex coronary artery (Cx) branches, 102 (21.20%) to the right coronary
      artery (RCA), 108 (22.46%) to the Di. The mean graft number was 3.46. We used
      96.6% of patients' left internal mammarian artery (LITA), 29.2% radial artery
      (RA), 4.4% right internal thoracic artery (RITA), and 100% saphenous vein. There
      were ischemic changes within 12 patients. All ischemic changes came back to
      normal within 4 and 18 hours, postoperatively. Mean extubation time was 5.36 +/-
      2.23 hours, mean stay in intensive care unit was 17.53 +/- 3.15 hours, mean
      hospital stay was 5.03 +/- 1.29 days. The LITA patency was 99.25%, RA patency was
      97.84%, RITA patency was 100%, and saphenous vein patency was 91.79% with control
      angiography. CONCLUSION: Off-pump coronary artery bypass graft (CABG) is
      efficient procedure with lower index of mortality, morbidity, ICU stay, hospital
      stay, good wound healing, early socialization, and results in lower costs.

PMID- 16426339
TI  - Elective intraaortic balloon counterpulsation in high-risk off-pump coronary
      artery bypass grafting.
AB  - The beneficial effects of intraaortic balloon pump (IABP) in CABG with
      cardiopulmonary bypass (CPB) have been reported. However, the benefits of
      insertion of IABP electively in high-risk off-pump coronary artery bypass
      grafting (OPCAB) have not been established. Six hundred and twenty-five patients
      who underwent OPCAB form the study group. High-risk patients fulfilling two or
      more of the following: left main stem stenosis >70%, unstable angina, and poor
      left ventricular function, who had elective insertion of IABP preoperatively by
      the open technique (group I; n = 20) were compared with a similar high-risk group
      that did not (group II; n = 25). There were no significant differences in risk
      factors between the two groups (Euroscore 5.68). The mean number of grafts was
      similar. Postoperatively, there were no significant differences in the need for
      inotropes, duration of ventilation, arrhythmias, cerebrovascular,
      gastrointestinal, and infective complications (p = NS). There were no IABP
      related complications. Acute renal failure requiring hemofiltration was higher in
      group II (n = 5; p < 0.05). Four patients (16%) in group II required
      postoperative IABP. Although intensive care stay was longer in group I (27.6 +/-
      15.3 vs. 18.6 +/- 9.1 hours; p < 0.05), patients in group I were discharged
      earlier from hospital. There was no difference in mortality between the two
      groups (n = 1 in each group). In high-risk patients undergoing OPCAB, routine
      preoperative insertion of IABP electively reduces the incidence of acute renal
      failure. In addition it avoids the need for emergency insertion postoperatively
      and may result in earlier discharge.

PMID- 16426341
TI  - Right ventricular function after coronary surgery with or without bypass.
AB  - BACKGROUND AND OBJECTIVE: Myocardial protection during aortic clamp period may
      sometimes be inadequate, especially for the right. The aim of this study was to
      compare right ventricle function after cardiac surgery with or without bypass.
      METHODS: Patients undergoing multivessel coronary surgery with proximal severe
      right coronary lesion were included in a prospective observational cohort study
      including 29 patients undergoing coronary surgery with or without bypass. All
      patients were monitored with a pulmonary artery catheter with continuous right
      ventricular function. Right ventricular ejection fraction was measured at the
      arrival in ICU, 1, 3, 6, and 18 hours later. RESULTS: The number of grafts that
      was higher in the bypass group (4.0 +/- 1.3) than in the off-pump group (2.6 +/-
      0.6, p = 0.001). In the on-pump group, the right ventricular ejection fraction
      significantly decreased from 32.9 +/- 2.8 at arrival in ICU to 26.1 +/- 2.4, 6
      hours later whereas in the off-pump group, it did not significantly change (32.4
      +/- 1.8 to 31.9 +/- 2.3). Meanwhile, at the same time intervals, CVP was
      significantly lower in the off-pump group. CONCLUSIONS: In patients with severe
      right coronary stenosis, off-pump cardiac surgery seemed to provide better right
      ventricular protection.

PMID- 16426342
TI  - Effect of aprotinin on postoperative blood loss in off-pump coronary artery
      bypass surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: Off-pump coronary artery bypass (OPCAB) enables
      a reduction in postoperative complications, particularly bleeding and
      transfusion. Nevertheless, a significant percentage of patients still needs
      transfusion. The effect of antifibrinolytic therapy on postoperative bleeding as
      part of OPCAB is still not widely described. The purpose of this study was to
      investigate the potential benefit of aprotinin in OPCAB. METHODS: We conducted a
      retrospective comparative study with a historical control group. Consecutive
      patients undergoing off-pump coronary bypass were divided in two groups: 40
      patients were operated without any antifibinolytic drug (group C); 40 patients
      received aprotinin (group A) during surgery. Patients in group A received a bolus
      of 2 x 10(6) KIU during 30 minutes, followed by a continuous infusion of 0.5 x
      10(6) KIU per hour until the end of surgery. The same protocol was used during
      the whole study period. RESULTS: Preoperative data of the two groups did not
      differ except for the number of grafts performed, which was higher in group A.
      Prothrombin time and activated clotting time increased in both groups after
      surgery. The use of packed red blood cells or fresh frozen plasma was not
      significantly different between both groups. Postoperative blood loss was
      significantly reduced in the aprotinin group (540 mL +/- 320 vs. 770 mL +/- 390,
      p = 0.006). No increase in postoperative troponin values was found in group A.
      CONCLUSIONS: Aprotinin significantly reduced postoperative blood loss without
      reducing the transfusion rate. Aprotinin was not associated with any increase in
      postoperative complications.

PMID- 16426343
TI  - Myocardial revascularization in patients with low ejection fraction < or =35%:
      effect of pump technique on early morbidity and mortality.
AB  - BACKGROUND AND AIM: Left ventricular dysfunction is an important predictor of in
      hospital mortality. Surgical risk among these patients remains high. The present
      study is conducted to evaluate the difference in early morbidity and mortality
      among patients with compromised left ventricular function (LVF) after myocardial
      revascularization using either off-pump or on-pump coronary artery bypass graft.
      METHODS: Between April 2000 and April 2004, 150 patients with ejection fraction
      (EF) < or =35% underwent isolated coronary artery bypass grafting. Eighty-four
      patients underwent conventional bypass (mean EF 30.1%+/- 4.2) and 66 patients had
      off-pump coronary artery bypass (mean EF 27.5%+/- 5.5). Different variables
      (preoperative, intraoperative, and postoperative) were evaluated and compared.
      Determination of operation risk was done using EuroSCORE. Patients who underwent
      OPCAB were more risky due to a high percentage of associated comorbidities, mean
      EuroSCORE was 12.96 +/- 13.21 in comparison to 8.47 +/- 10.22 in CCAB. RESULTS:
      The mean operative mortality was 8.7%. Patients who underwent OPCAB had a lower
      operative mortality than CCAB (6.1% vs. 10.7%) inspite of a higher preoperative
      predicted risk score. Completeness of revascularization was higher among the CCAB
      group (85.7% vs. 69.7%; p = 0.01). Subsequently, the mean number of grafts was
      significantly higher among this group (3.4+/-0.7 vs. 2.0 +/-0.9; p < 0.001). On
      the other hand, morbidity was significantly higher in CCAB (35.7% vs. 19.7%; p =
      0.03). However, the incidence of both myocardial infarction and atrial
      fibrillation was more among OPCAB. CONCLUSIONS: Patients with left ventricular
      dysfunction are high-risk group. These patients can benefit from myocardial
      revascularization using either off-pump or conventional CABG, but both are
      associated with a higher mortality and morbidity than those with normal
      ventricle. The use of off-pump CABG resulted in better clinical outcome and
      mortality, but less number of grafts performed than those with conventional CABG
      especially in patients with lowest EF.

PMID- 16426344
TI  - Predictors of mid-term symptom recurrence, adverse cardiac events and mortality
      in 591 unselected off-pump coronary artery bypass graft patients.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) grafting is gaining
      popularity; however, decreased mid-term graft patency and increased coronary
      reintervention rates are reported. STUDY DESIGN: Five hundred and ninety-one
      consecutive unselected patients underwent OPCAB grafting from February 2000 to
      April 2004 (mean follow-up 38.54 +/- 0.54 months). One hundred and thirteen
      patients had < or =2 grafts, and four hundred and seventy-eight had > or =3
      grafts. At least one radial artery graft was present in 398 patients, 328
      received postoperative Clopidogrel, and 391 received postoperative statins.
      History of at least one percutaneous coronary intervention (PCI) was present in
      192 patients. RESULTS: Twenty-nine patients developed recurrent angina, nine had
      myocardial infraction, and twenty underwent coronary reintervention. Five
      patients died of sudden cardiac death. Overall mortality was 4.9% during follow
      up (29 patients). Postoperative Clopidogrel and statins as well as intraoperative
      shunt use significantly decreased symptom recurrence and adverse cardiac events.
      Diabetes, chronic obstructive pulmonary disease, prior history of PCI, and
      utilization of radial artery grafts were positive predictors of symptom
      recurrence and adverse cardiac events. Utilization of radial artery grafts,
      history of PCI as well as low preoperative ejection fraction increased mortality.
      Number of bypass grafts, type of conduit, grafted territory, hyperlipidemia, or
      prior coronary artery bypass graft surgery (CABG) did not influence symptom
      recurrence, adverse cardiac events or mortality. CONCLUSIONS: OPCAB grafting can
      be performed with low symptom recurrence, adverse cardiac events, and mortality
      rates. Modification of intra- and postoperative management strategies may improve
      outcomes.

PMID- 16426345
TI  - Impact of off-pump coronary artery bypass surgery on postoperative bleeding:
      current best available evidence.
AB  - Cardiopulmonary bypass (CPB) is a prerequisite for open-heart surgery, and is a
      procedure routinely used. CPB exposes blood to artificial surfaces, to mechanical
      trauma from the pump, to alterations in temperature, and to dilution with fluids,
      whole blood, plasma products, and drugs, and leads to the activation of
      platelets, coagulation, and fibrinolysis. Coagulopathy during cardiac surgery
      with CPB results in impairment in hemostasis and subsequently higher morbidity
      and mortality. Recent advances in surgical techniques and postoperative
      management have aimed at reducing postoperative morbidity and mortality. Off-pump
      coronary artery bypass (OPCAB) surgery is one such advance that attempts to avoid
      the deleterious effects of extracorporeal circulation by performing myocardial
      revascularization without CPB. Emerging evidence from several randomized
      controlled trials (RCTs) as well as large registries such as the Society of
      Thoracic Surgeons (STS) database suggests that OPCAB reduces the postoperative
      morbidity and mortality. This review article attempts to evaluate the current
      best available evidence from RCTs on the impact of OPCAB on postoperative
      bleeding and transfusion requirements.

PMID- 16426347
TI  - The role of zofenopril in myocardial protection during cardioplegia arrest: an
      isolated rat heart model.
AB  - BACKGROUND: Zofenopril has beneficial effects in acute myocardial infarction, and
      improves the functional recovery after ischemia and reperfusion. AIM OF THE
      STUDY: The aim of this study was to investigate the cardioprotective effects of
      zofenopril, when added to a standard cardioplegic solution or when orally
      administered as pretreatment. METHODS: A Langendorff model for isolated rat
      hearts was employed: three groups of eight hearts each were used, respectively,
      with plain St. Thomas cardioplegia as control (group A and C), and the same
      solution added with 12.5 mg of zofenopril (group B). The third group (C) was
      pretreated for 7days with oral administration of zofenopril (6.5 mg/day). The
      hearts had a baseline perfusion for 30 minutes with Krebs-Henseleit solution at
      37 degrees C, cardioplegia administration for 3 minutes, then 30 minutes of
      ischemia without any perfusion, and finally 30 minutes of reperfusion with Krebs
      Henseleit solution at 37 degrees C. RESULTS: Left ventricle developed pressure
      was significantly higher in the reperfusion period only in the pretreated group
      (group C) with respect to groups A and B (p = 0.016). Similar results were
      obtained regarding dP/dt curves (p = 0.020). No differences were demonstrated
      between groups for cellular viability expressed as creatine phospho-kinase (p =
      ns) and lactate dehydrogenase release (p = ns). CONCLUSIONS: Zofenopril as oral
      pretreatment showed protective effects in an isolated model of cardioplegic
      arrest, although improvements in myocardial viability (enzymatic release) could
      not be demonstrated. Further experimental and clinical evaluations are necessary
      to assess the direct cardioprotective effect of zofenopril, modifying the length
      of treatment and the dosage of the drug.

PMID- 16426348
TI  - An ovine model of chronic heart failure: echocardiographic and tissue Doppler
      imaging characterization.
AB  - BACKGROUND AND AIM OF THE STUDY: Heart failure in the western world is a major
      health-care issue. In order to validate novel surgical or pharmacological
      treatments, reproducible animal models of left ventricular dysfunction are
      necessary. In the current study, we report our data and experience with a model
      of toxin-induced heart failure in the sheep. METHODS: Sequential intracoronary
      injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until
      standard echocardiographic and tissue Doppler imaging detection of myocardial
      systolic dysfunction. The animals were assessed 1 month later and harvested.
      Indices of cardiac function from baseline to last day of protocol were recorded
      and their differences were evaluated by a Wilcoxon rank test for paired data.
      RESULTS: Ten sheep received 2.5 +/- 0.7 intracoronary injections of a cumulative
      dose of 88.8 +/- 25 mg/m2 doxorubicin. All available parameters demonstrated
      signs of severe cardiac dysfunction with statistical significance. All hearts
      demonstrated severe histological lesions, some of which were consistent with
      doxorubicin-induced toxicity. CONCLUSIONS: The present study shows that this
      ovine model is reproducible and stable. It can therefore be relevant to the study
      of chronic heart failure. It will be incorporated in our future studies
      concerning novel treatments (such as cell therapy) of nonischemic dilated
      cardiomyopathy.

PMID- 16426349
TI  - The effects of pentoxifylline on the myocardial inflammation and ischemia
      reperfusion injury during cardiopulmonary bypass.
AB  - BACKGROUND: Pentoxifylline (Ptx) decreases necessity of cell energy and
      inflammatory reactions via inhibition of 5'-nucleotidase (5'-NT). The aim of this
      study is to investigate whether the addition of Ptx into the cardioplegic
      solutions avoids myocardial inflammatory reactions and ischemia/reperfusion (I/R)
      injury during extracorpereal circulation. METHODS: Between December 1999 and
      February 2002, we operated 75 patients with the diagnoses of atrial septal defect
      (ASD), ventricular septal defect (VSD), valve disease, and coronary disease. The
      average age of patients was 42.4 and male-female ratio was 1: 1.5. The patients
      were divided into two groups, which were the study group (n = 40) and the control
      group (n = 35). We used cold blood cardioplegia mixed with St. Thomas' Hospital
      II cardioplegic solution for both of the groups. Ptx was added into the
      cardioplegic solution (500 mg/L) in the study group. Interleukin-6 (IL-6),
      interleukin-8 (IL-8), and tumor necrotisis factor-alpha (TNF-alpha) levels in
      coronary sinus blood samples during cross-clamp time (X-clamp) and after
      releasing of it and tissue TNF-alpha in the right atrial appendix biopsy material
      that was taken after X-clamp were studied to compare the both groups. RESULTS:
      After releasing X-clamp, results of blood TNF-alpha, IL-6, and IL-8 of both
      groups were statistically significant (p < 0.005). At the pathological
      examination, we also observed that the amount of tissue TNF-alpha in the control
      group (66 +/- 17.1) was much higher than the study group (16.6 +/- 5.9, p
      <0.005). CONCLUSIONS: These results show that Ptx may be added into cardioplegic
      solution to avoid the myocardial inflammation and I/R injury during open heart
      surgery.

PMID- 16426350
TI  - A more comprehensive left ventricular repair for severely dilated cardiomyopathy.
AB  - We report a patient with cardiogenic shock due to severely dilated cardiomyopathy
      who underwent complex, but comprehensive left ventricle (LV) repair. Preoperative
      investigation showed marked LV dilatation, poor LV function, severe mitral and
      tricuspid regurgitation, and total occlusion of two coronary arteries. We
      urgently performed (1) modified Batista operation which preserves the LV apex,
      (2) septal anterior ventricular exclusion (SAVE) operation, (3) mitral
      annuloplasty, (4) tricuspid annuloplasty, and (5) coronary bypass. Postoperative
      evaluation revealed good graft flow, reduced LV dimension preserving the
      elliptical shape, improved LV function, and minimal MR. Twenty-six months
      postoperatively, the patient has minimum clinical symptoms (NYHA: I).

PMID- 16426352
TI  - Simultaneous repair of acute ischemic VSD with LV remodeling.
AB  - We describe a patient successfully treated with simultaneous ventricular septal
      defect (VSD) repair and LV restoration procedure patch after developing both a
      VSD and LV dyskinesia following acute myocardial infarction. This procedure is
      technically challenging and represents a novel technique for the management of
      this clinical problem.

PMID- 16426353
TI  - Clampless arterial coronary artery bypass grafting with the use of magnetic
      coupling devices.
AB  - BACKGROUND: The aim of our study was to evaluate the feasibility of using the
      Ventrica MVP device to perform proximal anastomoses as part of the clampless off
      pump coronary artery bypass (OPCAB) arterial revascularization procedure.
      METHODS: We present our preliminary experience of these first nine coronary
      artery cases performed in the UK from April 2003 to December 2004. RESULTS: The
      device was used in eight patients for the proximal anastomosis of a radial artery
      (n = 8) or right internal thoracic artery (n = 1) graft as a Y-graft from the
      left internal thoracic artery to the circumflex territories. One patient died in
      this series although the autopsy showed that the device was intact and free of
      clots and the reported cause of death was an acute cardiac event due to
      myocardial ischemia. Anastomotic patency was confirmed in five patients with the
      use of multidetector row computed tomography coronary angiogram. The anastomosis
      time in our series was 6.3 +/- 2.1 minutes and the blood loss 814 +/- 245 mL. The
      mean length of stay was 5.2 +/- 1.2 days. No other significant major morbidity
      events were observed postoperatively (neurological complications, renal failure,
      and reopening for bleeding). The assessment of quality of life at 6 months
      postoperatively using SF-36 questionnaires revealed improvement. CONCLUSION: The
      versatile use of Ventrica MVP distal anastomotic device is feasible in clinical
      practice allowing surgeons to perform proximal anastomoses and arterial OPCAB
      surgery with short learning curve and without compromising the clinical outcome
      and quality of life.

PMID- 16426355
TI  - Asymptomatic cardiac papillary fibroelastoma: diagnostic assessment and therapy.
AB  - Papillary fibroelastoma is a rare benign cardiac tumor with elevated risk for
      embolization. This report describes the case of a 65-year-old man, admitted for
      the occasional finding of a round, pedunculate mass adherent to the chordae of
      the anterior mitral valve leaflet, mimicking an endocarditic mass. Appropriate
      diagnostic evaluations lead to the suspect of a papillary fibroelastoma. Because
      of the elevated risk of thromboembolism, surgery was emergently performed with
      complete removal of the mass and preservation of the integrity of the mitral
      valve. Histologic evaluation confirmed the diagnosis. Papillary fibroelastoma
      should be always considered in the differential diagnosis of intracardiac masses.

PMID- 16426356
TI  - Anomalous origin of the stenosed circumflex artery from the right coronary
      artery.
AB  - During recent years, anatomic variations of coronary arteries have been described
      with the aid of elective coronary arteriography. We report a case of anomalous
      origin of the stenosed circumflex artery from the right coronary artery. The
      patient was operated upon successfully, and the right internal mammary artery was
      placed on the circumflex artery.

PMID- 16426357
TI  - Robot-assisted isolation of the pulmonary veins with microwave energy.
AB  - BACKGROUND: Ablation of the left atrium to isolate the pulmonary veins has been
      shown to interrupt electrical foci that may induce atrial fibrillation. This
      study evaluated the feasibility of performing a minimally invasive left atrial
      isolation on a beating heart using the da Vinci Robotic Surgical System and a
      flexible microwave probe (Flex 10 by AFx, Inc., Fremont, CA, USA), and the
      reliability of exit block pacing to confirm transmurality of the lesions created.
      METHODS: On six canines, the Flex 10 probe was passed around the left atrium
      posterior to the superior vena cava, through the transverse sinus, and back
      through the oblique sinus via a right-chest-only approach using the da Vinci
      Robotic Surgical System. Prior to ablation, pacing outside the atrial cuff was
      confirmed. Ablation was then carried out on the beating heart and repeated (as
      needed) until electrical isolation was demonstrated by exit block pacing. Probe
      position was confirmed at the completion of the procedure via sternotomy.
      Analysis included acute histologic and gross examination of the targeted area.
      RESULTS: There was no significant difference (p = 0.110) in procedure time,
      although it decreased 39.6% from the first three cases to the last three cases.
      Electrical evidence of electrical left atrial isolation was achieved in all
      subjects. Acute histologic examination confirmed transmurality inconsistently.
      Additionally, in two animals, the Flex 10 probe was found to be anterior to the
      left atrial appendage. All animals survived the procedure. CONCLUSION: A
      minimally invasive left atrial isolation procedure using monopolar microwave
      energy with the da Vinci Robotic Surgical System is simple and feasible. However,
      despite creating an electrical block, transmurality was not demonstrated
      consistently and further confirmation of catheter positioning is necessary during
      a right-chest-only approach.

PMID- 16426358
TI  - Novel use of a magnetic coupling device to repair damage of the internal thoracic
      artery.
AB  - At present, there is limited reported literature on the use of the magnetic
      anastomotic device Ventrica MVP in the coronary artery bypass surgery setting.
      The device has been primarily used to perform distal coronary anastomoses. We
      report for the first time the novel use of this magnetic coupling device as a
      technique to repair iatrogenic injury of the left internal thoracic artery
      conduit. Technical issues, advantages, disadvantages, and the use of computer
      tomography angiogram for assessment of the anastomosis are discussed.

PMID- 16426359
TI  - OPCAB surgery after right pneumonectomy.
AB  - Coronary artery bypass grafting was performed in a 58-year-old patient 3 years
      after right pneumonectomy for nonsmall cell lung cancer stage IIIa. The CT scan
      demonstrated a marked shift of the mediastinum into the right chest, but revealed
      a feasible access to the left coronary artery by median sternotomy. Pulmonary
      function was impaired. Off-pump coronary artery bypass grafting was performed to
      avoid cannulation under more difficult conditions and to prevent negative side
      effects of cardiopulmonary bypass to the pulmonary function. The postoperative
      recovery was uneventful. We discuss issues related to this special subgroup of
      patients.

PMID- 16426362
TI  - Diffuse coronary artery disease and dystrophic calcification of the radial artery
      -is there an association?
AB  - Arterial revascularization is an attractive surgical option in the management of
      coronary artery disease (CAD). In the recent years, the radial artery (RA) has
      enjoyed resurgence in popularity as the preferred arterial conduit of choice
      after the internal mammary artery. Despite renewed interest in RA conduits,
      little is known of the prevalence of preexisting disease in this vessel, and in
      particular which patient subgroups are most affected, hence implications for long
      term graft patency remain uncertain. We present our experience of three patients
      with diffuse CAD, found to have dystrophic calcification of their radial arteries
      intraoperatively. In all cases, the radial arteries were used, and the patients
      remain well and symptom-free. Soft tissue X-rays of the contra lateral forearm
      taken postoperatively demonstrated obvious calcification in the radial arteries
      in all patients. Diffuse CAD may reflect calcific disease in the RA. Suitability
      of a calcified RA as a conduit for CABG depends on long-term patency, which
      requires further evaluation.

PMID- 16426360
TI  - Repair of acute postinfarct posterior ventricular septal rupture without left
      ventriculotomy: a stable suture preserving left ventricular geometry.
AB  - The present article describes the case of a man operated upon for emergency
      closure of an acute postinfarction defect in the posterior septum. We used a
      novel technique. The rupture was approached by disconnection of the right
      ventricular posterior free wall with the exposure of the right side of the
      septum. First, the edges of the defect were joined together by a single purse
      string pledgetted suture. Then an on-site tailored double-folded patch was
      applied with the aim of closing both the septal defect and the RV access. In our
      limited experience the technique proved to be safe and effective, allowed optimal
      exposure of the defect and placement of stable stitches, reducing postoperative
      complications.

PMID- 16426367
TI  - Value, access, relevance and the next 5 years.

PMID- 16426364
TI  - Radial artery graft for coronary artery bypass surgery: biological
      characteristics and clinical outcome.
AB  - The radial artery (RA) is gaining popularity as a bypass conduit for coronary
      artery bypass grafting, and its impact on clinical practice has been extensively
      explored. In the present article, we provide a review of postoperative hand
      circulation, vascular biological characteristics of the RA graft, the efficacy of
      vasodilator therapies, and mid-term clinical results of use of the RA graft.
      Fundamental studies revealed excellent vascular biological characteristics of the
      RA graft as a living arterial conduit, making it almost equivalent to the
      internal thoracic artery (ITA) graft. Clinical studies have yielded encouraging
      mid-term results. Most studies reported in favor of the RA graft over the
      saphenous vein graft with regard to patency rate, freedom from cardiac events,
      and survival. However, superiority of either the RA or right ITA graft has not
      been conclusively determined. The long-term results of RA grafts remain unknown,
      but at present, supplementary use of an RA graft with a left ITA graft appears
      feasible for CABG.

PMID- 16426368
TI  - Primary cutaneous small vessel vasculitis: approach to diagnosis and treatment.

PMID- 16426369
TI  - Mucocutaneous paraneoplastic syndromes in hematologic malignancies.

PMID- 16426370
TI  - Cutaneous adornment in the Yoruba of south-western Nigeria - past and present.
AB  - The traditional practice of cutaneous adornment is rich and vast amongst the
      Yoruba in the south-western part of Nigeria. There are varieties of traditionally
      made products, such as oils, soaps, fragrances, and beads, that have been
      employed over the years to enhance body beauty. This rich cultural heritage,
      however, has more or less given way to the values of Western culture, together
      with the disadvantages of the latter, manifesting as sequelae on the skin.

PMID- 16426371
TI  - Dermoscopic examination of the nail bed and matrix.
AB  - Abstract Background Dermoscopy has furthered advances in the differential
      diagnosis of longitudinal melanonychia; however, fewer details observed in the
      nail, as compared to skin lesions, make interpretation difficult. Methods Ten
      cases of longitudinal melancholia, from several etiologies, were submitted to
      direct dermoscopic examination of the nail bed and matrix. Results We observed
      the presence of globules, streaks, and pigment network in the nail bed and
      matrix, which are dermoscopic features not seen in the nail plate. Conclusions
      This procedure enables visualization of dermascopic features not seen in the nail
      plate, making the diagnosis of melanocytic lesions easier.

PMID- 16426372
TI  - Burden of Atopic dermatitis in Canada.
AB  - BACKGROUND: Atopic dermatitis (AD) is relatively common worldwide; costs
      associated with the disease have been reported recently for various countries,
      but no estimates of costs in Canada are currently available. The objective of
      this study was to estimate the costs associated with AD in Canada, assessed from
      resource use determined for a Canadian setting. METHODS: Seventy-six patients in
      Ontario with AD were surveyed to determine information about severity of disease,
      healthcare practitioner visits, over-the-counter medication use, household
      expenses and absenteeism relating to their condition. Based on this information,
      costs were determined based on the Ontario billing schedule, estimated
      prescription use, reported out-of-pocket expenses and stated family income. Data
      about sleep disturbance and concern over topical corticosteroid use were also
      obtained. RESULTS: Patients reported an average of 3.6 publicly funded doctor
      visits per year for AD; 58% of these visits were to general practitioners and 28%
      to dermatologists. The annual per patient expenditure was estimated to be 282,
      454 Canadian dollars and 1242 Canadian dollars for patients with mild, moderate
      and severe AD, respectively. The total cost of AD in Canada was estimated to be
      1.4 billion Canadian dollars annually. More than half of the patients experienced
      sleep disturbances owing to their condition, and 71% reported having concerns
      about topical corticosteroid use. CONCLUSIONS: Although the cost per patient of
      AD in Canada is relatively low, owing to the prevalence of the disease, the total
      cost to society is large. Most of the cost is borne by patients and their
      employers, primarily owing to indirect costs associated with absenteeism.

PMID- 16426373
TI  - A 10-year study of squamous cell carcinoma in Hamedan in the west of Iran (1993
      2002).
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the second most common
      form of skin cancer in Caucasians. Environmental factors, especially sunlight,
      play an important role in its pathogenesis. Aim To better define the frequency
      and characteristics of SCC in patients biopsied at Hamedan Sina Hospital in the
      west of Iran. METHODS: This descriptive cross-sectional study was carried out in
      patients diagnosed with SCC in the Department of Dermatology, Hamedan Sina
      Hospital, Hamedan, Iran, in the 10-year period from 1993 to 2002. RESULTS: From a
      total of 6846 biopsies, 669 skin cancers were diagnosed, including 449 (66.67%)
      basal cell carcinomas (BCC) and 179 (26.76%) SCC. The head and face were the most
      common sites of SCC location. Farming was the most common occupation. CONCLUSION:
      SCC is the second most common form of skin malignancy in the west of Iran.
      Sunlight may play a role in the etiology of this tumor.

PMID- 16426374
TI  - Cutaneous leishmaniasis in Yemen: clinicoepidemiologic features and a preliminary
      report on species identification.
AB  - OBJECTIVE: To study the clinicoepidemiologic profile of cutaneous leishmaniasis
      (CL) in Yemen (Hajjah and adjacent regions) and to identify the Leishmania
      species responsible. METHODS: All 136 cases [96 (70.6%) males and 40 (29.4%)
      females] were subjected to detailed analysis. The diagnosis was based on positive
      slit skin smear and histopathologic studies when needed. In four cases, in vitro
      culture and Leishmania characterization by isoenzyme electrophoresis of 15
      isoenzymes were attempted. RESULTS: Most of the patients (107; 78.7%) were
      residents of the Hajjah Governorate. The majority of the patients had a single
      noduloulcerative lesion on the face. Slit skin smear was positive for parasites
      in 128 (94%) cases (highly positive in 63 cases) and four Leishmania isolates
      were obtained. The isoenzyme characterization results revealed L. tropica to be
      the species responsible, and zymodeme analysis showed that one strain belonged to
      zymodeme MON137, and three strains belonged to two previously undescribed
      zymodemes similar to zymodeme MON71. CONCLUSION: CL seems to be endemic in this
      region. L. tropica was identified as the species responsible in four strains.

PMID- 16426376
TI  - "More is missed by not looking than by not knowing"[Thomas McCrae, 1870-1935].
AB  - CASE 1: A 19-year-old woman presented with a black crust on one part of the
      tattoo on her right leg (Fig. 1) which appeared after laser-assisted hair removal
      by an alexandrite laser (755 nm). CASE 2: A 28-year-old man underwent laser
      assisted hair removal from his back and shoulders by an alexandrite laser (755
      nm), after which he developed a burn on part of the tattoo on his right shoulder
      and was left with an atrophic scar (Fig. 2).

PMID- 16426375
TI  - Cutaneous leishmaniasis: successful treatment with itraconazole.
AB  - BACKGROUND: Leishmaniasis is a disease produced by several species of protozoa of
      the Leishmania genus. These protozoa are injected into the human bloodstream by
      sandflies. The symptomathology, either cutaneous, mucocutaneous or visceral,
      depends on the infective species and the immune status of the patient. Antimonial
      drugs are the mainstay treatment for all the clinical forms of the disease.
      Amphotericin B is the second-choice drug. METHODS: We report two clinical cases
      of cutaneous leishmaniasis treated with itraconazole. One case was a relapsing
      form unresponsive to conventional therapy. RESULTS: Both patients achieved fast
      resolution of their lesions with no secondary effects. CONCLUSIONS: Itraconazole
      may be a valid option for the treatment of cutaneous leishmaniasis, mainly in
      those cases unresponsive to conventional drugs.

PMID- 16426377
TI  - Neutrophilic dermatosis of the dorsal of the hands: acral sweet syndrome?

PMID- 16426378
TI  - Retiform hemangioendothelioma presenting as bruise-like plaque in an adult woman.

PMID- 16426379
TI  - Nephrogenic fibrosing dermopathy in a patient with acute renal failure never
      requiring dialysis.
AB  - Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrosing
      disorder. To date the etiology, pathogenesis, and clinical course remains
      unknown. The majority of cases have been in renal dialysis or renal transplant
      patients. Only four cases have been reported in which patients had acute renal
      failure and never required dialysis. Currently, there is no effective treatment.
      A 65-year-old man was hospitalized for pneumonia. During hospitalization he
      developed acute renal failure secondary to acute tubular necrosis. The patient
      had woody indurated plaques on his upper extremities and trunk, and brown
      indurated plaques on his trunk. Histopathological examination revealed a spindle
      cell proliferation infiltrating through the dermis and subcutis with mild mucin
      deposition. Nephrogenic fibrosing dermopathy is a novel fibrosing disorder
      diagnosed clinically and histopatholigically. Currently no risk factors other
      than renal failure have been identified. Our patient is a unique example of NFD
      observed in acute renal failure secondary to acute tubular necrosis, never
      requiring dialysis. We also review the four other cases of acute NFD never
      requiring dialysis that have been reported in the literature.

PMID- 16426380
TI  - Sclerosing dermatofibrosarcoma protuberans (DFSP): an unusual variant with focus
      on the histopathologic differential diagnosis.
AB  - A 59-year-old man presented with a 10-cm x 8-cm tumoral plaque with a superficial
      nodule in the interscapular region of the back (Fig. 1). The lesion had been
      growing for 25 years. As a cystic lesion was suspected, the superficial nodule
      was biopsied. The histopathologic diagnosis was low-grade sarcoma with sclerosis.
      Two months after the initial biopsy, the lesion was completely excised, reaching
      the muscular fascia, with a 2-cm margin and with a free graft. Formalin-fixed
      paraffin-embedded samples were submitted to histologic and immunohistochemical
      study (4-microm paraffin sections); frozen tissue was submitted to electron
      microscopy. For histopathology, sections were stained with hematoxylin and eosin.
      Immunohistochemistry was performed following standard avidin-biotin
      immunoperoxidase procedures with primary antibodies for vimentin, CD34, smooth
      muscle-specific actin, bcl-2, S-100, desmin, myoglobin, factor VIII, p53 (all
      from DAKO, Copenhagen, Denmark), HHF-35 (Enzo Diagnostics, Farmingdale NY),
      cytokeratin (AE1/AE3) (Biogenex, San Ramon, CA), and factor XIIIa (Calbiochem
      Novabiochem Corporation, La Jolla, CA). At low magnification, the histologic
      study of the initial tumoral nodule revealed a poorly circumscribed mesenchymal
      proliferation, with fibroblastic-like neoplastic cells arranged in a fascicular
      and storiform pattern, admixed with extensive areas of sclerosis. At higher
      magnification, tumoral cells were spindle-shaped with hyperchromatic nuclei and
      scant cytoplasm. In some areas, sclerosis was so evident that a keloid-like
      pattern was seen (Fig. 2a). The surgical specimen showed a fibroblastic
      neoplastic proliferation infiltrating the dermis and hypodermis. In the dermis,
      cells were arranged in a storiform pattern, whereas in the hypodermis there was a
      honeycomb or lace-like pattern (Fig. 2b). There were also cellular areas
      alternating with sclerotic areas, with transitional zones in between, in both the
      dermis and hypodermis. The immunohistochemical study of the initial tumoral
      nodule and the surgical specimen showed that tumoral cells expressed vimentin,
      CD34 (Fig. 3), bcl-2, HHF-35, and smooth muscle actin. Neoplastic cells failed to
      show positivity with desmin, myoglobin, factor XIIIa, factor VIII, S-100,
      cytokeratin (AE1/AE3), and p53. An ultrastructural study revealed spindle cells
      having an irregular contour with a well-developed granular reticulum endoplasmic
      (REG) system in their cytoplasm, as well as some Golgi complexes and
      mitochondria. Also visible was the presence of many actin filaments and some
      myosin condensations (Fig. 4), characteristics of a fibroblastic cell with
      myofibroblastic differentiation. The final histopathologic diagnosis of the
      surgical specimen was sclerosing dermatofibrosarcoma protuberans. Two years after
      surgery, the patient is alive and well.

PMID- 16426381
TI  - Treatment of vitiligo with broadband ultraviolet B and vitamins.
AB  - BACKGROUND: While oral psoralen plus ultraviolet A (PUVA) remains the most
      popular therapeutic modality for vitiligo, recent reports have shown that
      narrowband ultraviolet B (UVB) also induces significant repigmentation. In this
      study we evaluated the efficacy of broadband UVB on actively spreading,
      progressive vitiligo in patients who had been followed for many months (12 or
      more) in our practice, who continued to depigment despite treatment. METHODS:
      Nine patients with actively spreading vitiligo were exposed to broadband UVB 2-3
      times per week at a starting dose of 20-30 mJ/cm(2). Radiation was increased by
      10-20 mJ/cm(2) per session with adjustments for symptomatic erythema or missed
      visits. In addition, patients took vitamin C 500 mg twice a day (BID), vitamin
      B(12) 1000 microg BID and folic acid 5 mg BID. The response to treatment and side
      effects were assessed at each visit. The patient's response to treatment and
      progress were assessed by photographs and by physician evaluation of body surface
      area (BSA) (using the Rule of 9s) involved at monthly intervals. Photographs were
      taken and estimations of BSA by physical examination made at the start and finish
      of the trial and then compared by the physicians involved in the study. RESULTS:
      Broadband UVB halted the progression of vitiligo in all nine patients and in
      general induced repigmentation early after 8-12 treatments (6-8 weeks). After 2-8
      months of treatment, nine of nine patients achieved good (51-75%) or excellent
      response (76-100%). The percentage of repigmentation varied with length of
      treatment and anatomic site. CONCLUSIONS: This study confirms the only published
      report that broadband UVB is effective on actively spreading vitiligo. Since it
      is more cost effective than narrowband UVB and has numerous advantages compared
      to oral PUVA, broadband UVB may offer an alternative for future treatment of
      vitiligo. The role of vitamins in this therapy remains to be determined.

PMID- 16426382
TI  - Ciclopirox 1% shampoo for the treatment of seborrheic dermatitis.
AB  - Seborrheic dermatitis is a chronic superficial fungal infection of the skin,
      particularly affecting sites rich in sebaceous glands. Although the precise
      etiology of seborrheic dermatitis is uncertain, yeasts of the genus Malassezia
      are known to play a causative role. Ciclopirox is a broad-spectrum,
      hydroxypyridone-derived, synthetic antifungal agent, which also has anti
      inflammatory properties. Ciclopirox is effective both in vitro and in vivo
      against Malassezia yeasts, making it a valuable option for the treatment of
      seborrheic dermatitis. Varying frequencies and concentrations of ciclopirox
      shampoo have been shown to be effective and safe in the treatment of seborrheic
      dermatitis of the scalp.

PMID- 16426383
TI  - Granuloma annulare, relapsing polychondritis, sarcoidosis, and systemic lupus
      erythematosus: conditions whose dermatologic manifestations may occur as
      hematologic malignancy-associated mucocutaneous paraneoplastic syndromes.

PMID- 16426384
TI  - Mnemonics in dermatology.

PMID- 16426385
TI  - Kawasaki disease in a US army soldier highlights surveillance.

PMID- 16426386
TI  - Efficacy of topical tacrolimus in the treatment of various cutaneous
      manifestations of lupus erythematosus.

PMID- 16426387
TI  - Prevalence of human cytomegalovirus DNA in scleroderma skin tissue.

PMID- 16426388
TI  - Multiple basal cell carcinomas in a patient with myotonic dystrophy type 1.

PMID- 16426390
TI  - Cerebral diffusion-weighted magnetic resonance imaging: a tool to monitor the
      thrombogenicity of left atrial catheter ablation.
AB  - INTRODUCTION: Cerebral embolism and stroke are feared complications of left
      atrial catheter ablation such as pulmonary vein (PV) ablation. In order to assess
      the thrombogenicity of left atrial catheter ablation, knowledge of both
      clinically evident as well as silent cerebral embolism is important. The aim of
      the current study was to examine the use of diffusion-weighted magnetic resonance
      imaging (DW-MRI) for detection of cerebral embolism, apparent as well as silent,
      caused by PV catheter ablation. METHODS AND RESULTS: Twenty consecutive patients
      without structural heart disease undergoing lasso catheter-guided ostial PV
      ablation using an irrigated-tip ablation catheter were studied. Cerebral MRI
      including DW single-shot spin echo echoplanar, turbo fluid attenuated inversion
      recovery, and T2-weighted turbo spin echo sequences were performed the day after
      the ablation procedure. Ten patients also underwent preprocedure cerebral MRI.
      All ablation procedures were performed without acute complications. A mean of 3.2
      +/- 0.6 PVs were ablated per patient. No patient had neurological symptoms
      following the procedure. In 2 of 20 patients (10%), DW-MRI revealed new embolic
      lesions, which were located in the right periventricular white matter in one and
      in the left temporal lobe in the other patient. There was no statistically
      significant difference in age, history of hypertension, left atrial volume, and
      procedure duration between the 2 patients with and the 18 patients without
      cerebral embolism following AF ablation. CONCLUSION: This is the first study
      using highly sensitive DW-MRI of the brain to detect asymptomatic cerebral
      embolism after left atrial catheter ablation. Even small, clinically silent,
      embolic lesions can be demonstrated with this technique. DW-MRI can be used to
      monitor and compare the thrombogenicity of different AF ablation approaches.

PMID- 16426391
TI  - Silent cerebral thromboembolism with left atrial ablation: a lurking danger.

PMID- 16426393
TI  - Athletes and ICDs: what to do when the clinical community disagrees with the
      "experts".

PMID- 16426392
TI  - Safety of sports participation in patients with implantable cardioverter
      defibrillators: a survey of heart rhythm society members.
AB  - Safety of Sports for ICD Patients. INTRODUCTION: The safety of sports
      participation for patients with implantable cardioverter defibrillators (ICDs) is
      unknown, and recommendations among physicians may vary widely. The purposes of
      this study were to determine current practice among patients with ICDs and their
      physicians regarding sports participation, and to determine how many physicians
      have cared for patients who have sustained adverse events during sports
      participation. METHODS AND RESULTS: A survey was mailed to all 1,687 U.S.
      physician members of the Heart Rhythm Society. Among 614 respondent physicians,
      recommendations varied widely. Only 10% recommended avoidance of all sports more
      vigorous than golf. Seventy-six percent recommended avoidance of contact, and 45%
      recommend avoidance of competitive sports. Most (71%) based restrictions on
      patients' underlying heart disease. Regardless of recommendations, most
      physicians (71%) reported caring for patients who participated in sports,
      including many citing vigorous, competitive sports, most commonly cited were
      basketball, running, and skiing. ICD shocks during sports were common, cited by
      40% of physicians. However, few adverse consequences were reported. One percent
      of physicians reported known injury to patient (all but 3 minor); 5%, injury to
      the ICD system, and <1%, failure of shocks to terminate arrhythmia. The most
      common adverse event reported was lead damage attributed to repetitive-motion
      activities, most commonly weightlifting and golf. CONCLUSIONS: Physician
      recommendations for sports participation for patients with ICDs varies widely.
      Many patients with ICDs do participate in vigorous and even competitive sports.
      While shocks were common, significant adverse events were rare.

PMID- 16426394
TI  - Catheter ablation of regular atrial arrhythmia following surgical treatment of
      permanent atrial fibrillation.
AB  - Ablation of Atrial Tachycardia after Antiatrial Fibrillation Surgery.
      INTRODUCTION: Surgical treatment of atrial fibrillation (AF) is gaining
      widespread acceptance. However, therapeutic modalities for secondary regular
      atrial tachycardia are still empiric. METHODS AND RESULTS: After linear atrial
      cooled-tip radiofrequency ablation (SICTRA) during cardio-surgical procedures to
      cure permanent AF, patients with regular atrial tachycardia were identified.
      Invasive electrophysiology including electroanatomic mapping was performed.
      Catheter ablation was directed to suppress atrial arrhythmia depending on
      activation mapping findings. Follow-up was performed after 3 months and then
      after every 6 months. Of 238 patients, 12 (5.0%) were identified with regular
      secondary arrhythmias (12 +/- 7 months after surgery) including 9 (3.8%) with
      persistent forms originating from the right atrium (RA) in six (66%) (isthmus
      dependent macroreentry in 4, incisional macroreentry in 1, and RA ectopy in 1).
      All patients with RA origin of the tachycardia were successfully ablated. Two
      patients had left atrial (LA)-macroreentry circling around the mitral valve
      indicating insufficiency of the intraoperative ablation procedure: one patient
      was successfully ablated within the LA isthmus, in the other patient no complete
      conduction block could be induced. One patient had LA-macroreentry degenerating
      into AF, and ablation was not performed. During follow-up (9 +/- 4 months), no
      recurrences of atrial tachycardias were documented after successful ablation.
      CONCLUSIONS: Persistent regular "secondary" arrhythmia occurred in 3.8% (9/238)
      of patients after SICTRA to treat permanent AF. Predominantly (67%; 6/9), the
      arrhythmia was located in the RA mostly incorporating the RA-isthmus. Catheter
      ablation was highly effective for RA tachycardia (100%). In three cases (33%), LA
      macroreentry was documented and catheter ablation was successful in only one
      patient (overall success 78%).

PMID- 16426395
TI  - Reanalysis of the "pseudo A-A-V" response to ventricular entrainment of
      supraventricular tachycardia: importance of his-bundle timing.
AB  - BACKGROUND: The sequence of atrial and ventricular electrograms following
      termination of ventricular pacing during supraventricular tachycardia has been
      shown to reliably differentiate atrial tachycardia from atrioventricular nodal
      reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT).
      However in patients with long HV intervals, this may be misleading due to a
      pseudo "A-A-V" response. The aim of the present study is to see if inclusion of
      the timing of the His-bundle in the electrogram response (ER) following
      ventricular pacing would reliably identify the mechanism of tachycardia in
      patients with long HV intervals. METHODS: Eight patients (7 men) with AVNRT and
      underlying bundle branch block and long HV (>55 msec) intervals underwent
      ventricular pacing at 10-40 msec shorter than the tachycardia cycle length during
      SVT. The ER was classified as "A-A-H" or "A-H" depending on the number of atrial
      electrograms (A) prior to His deflection following VEP. RESULTS: The ER following
      ventricular pacing was classified as A-H in all 8 patients. However, using
      conventional classification the response was A-A-V in 5 of 8 patients due to
      delayed ventricular activation secondary to long HV intervals and would
      erroneously suggest atrial tachycardia. The ER was A-V in only 1 of 8 patients.
      In the remaining 2 patients the A and V electrograms were simultaneous.
      CONCLUSIONS: Incorporating the His-bundle in the ER following ventricular pacing
      would eliminate the pseudo "A-A-V" response in patients with AVNRT and long HV
      intervals. Labeling the response to ventricular pacing as "A-H" or "A-A-H" is
      simple and more accurate.

PMID- 16426396
TI  - A feasible approach for direct his-bundle pacing using a new steerable catheter
      to facilitate precise lead placement.
AB  - INTRODUCTION: Much clinical evidence has shown that right ventricular (RV) apical
      pacing is detrimental to left ventricular function. Preservation of the use of
      the His-Purkinje (H-P) system may be ideal in heart block that is restricted to
      the AV node, but may be of no benefit when H-P disease exists. AIM: To
      investigate the feasibility of direct His-bundle pacing (DHBP) using a new system
      consisting of a steerable catheter and a new 4.1 F screw-in lead. METHOD: Between
      May and December 2004, 26 patients (19 male, mean age: 77 +/- 5 years) with a
      standard pacemaker (PM) indication and preserved His-bundle conduction were
      enrolled and DHBP was attempted. RESULTS: DHBP was achieved in 24 patients (92%);
      two patients were paced in the His area, but the paced QRS morphology and
      duration were different from the native QRS. The mean time for lead positioning
      was 19 +/- 17 minutes, the mean fluoroscopy time was 11 +/- 8 minutes, and the
      total procedure time (skin-to-skin including positioning of a quadripolar
      diagnostic catheter for His recording) was 75 +/- 18 minutes. In DHBP pacing, the
      acute pacing threshold was 2.3 +/- 1.0 V at a pulse duration of 0.5 msec, and the
      sensed potentials were 2.9 +/- 2.0 mV. At a 3-month follow-up examination, the
      same QRS duration and morphology recorded on implantation were observed in all
      patients. The pacing threshold was 2.8 +/- 1.4 V, and sensed potentials were 2.5
      +/- 1.8 mV; the sensing configuration was changed from bipolar to unipolar in 6
      patients to resolve undersensing issues. No major complications were observed.
      CONCLUSIONS: This feasibility study shows that DHBP can be accomplished with a
      new system consisting of a steerable catheter and an active fixation lead in 92%
      of the patients in whom it was attempted.

PMID- 16426397
TI  - Widespread electroanatomic alterations of right cardiac chambers in patients with
      myotonic dystrophy type 1.
AB  - INTRODUCTION: Conduction disturbances and arrhythmias characterize the cardiac
      feature of myotonic dystrophy type 1 (MD1); a myocardial involvement has been
      suggested as part of the cardiac disease. The aim of our study was to investigate
      the underlying myocardial alterations using electroanatomic mapping (CARTO) and
      their possible correlation with genetic and neurological findings. METHODS AND
      RESULTS: Right atrial and ventricular CARTO maps were obtained in 13 MD1
      patients. Thirteen age-matched patients with paroxysmal supraventricular
      tachycardia and normal heart served as controls. Unipolar voltage (UNI-v),
      bipolar voltage (BI-v) amplitudes, bipolar potential duration (Bi-dur), and
      atrial propagation time (A-pt) were measured. UNI-v and BI-v in interatrial
      septum, anterolateral atrial wall, and right ventricle outflow tract were lower
      in MD1 patients than controls (P < 0.001). Bi-dur and A-pt were longer in MD1
      patients than controls (P < 0.001, P = 0.046, respectively). A significant
      relationship was documented between CTG triplets and the percentage of Bi-v <0.5
      mV in the atrial anteroseptal region (r = 0.6, P = 0.02). CONCLUSIONS: Altered
      electroanatomic patterns are present in the right cardiac chambers in MD1
      patients. Widespread myocardial alterations, not necessarily limited to the
      conduction system, may support the presence of a cardiac myopathy as part of the
      disease.

PMID- 16426398
TI  - A multicenter experience with novel implantable cardioverter defibrillator
      configurations in the pediatric and congenital heart disease population.
AB  - INTRODUCTION: In pediatric and congenital heart disease patients, transvenous ICD
      implantation may be limited secondary to patient size, venous, or cardiac
      anatomy. Epicardial patches require a thoracotomy, and may lead to a restrictive
      pericardial process. Because of these issues, we have explored novel ICD
      configurations. METHODS: Retrospective review at 10 centers implanting ICDs
      without a transvenous shocking coil or epicardial patches. RESULTS: Twenty-two
      patients underwent implant at a mean age of 8.9 years (range: 0.3-43.5), with a
      mean weight of 25.5 kg (range: 5.2-70). Diagnoses included complex CHD,
      intracardiac tumors, cardiomyopathy, idiopathic VT, LV noncompaction, and long QT
      syndrome. Three configurations were used: subcutaneous array, a transvenous
      design ICD lead placed on the epicardium, or a transvenous design ICD lead placed
      subcutaneously. Difficulties were found at implant in 8 patients: 4 had
      difficulty inducing VT/VF, and 4 had high DFTs. Over a mean follow-up of 2.2
      years (range: 0.2-10.5), 7 patients had appropriate shocks. Inappropriate shocks
      occurred in 4 patients. System revisions were required in 7 patients: 2 generator
      changes (in 1 patient), 3 pace-sense lead replacement, 1 additional subcutaneous
      coil placement due to increased DFT, 1 upgrade to a transvenous system, and 1
      revision to epicardial patch system. CONCLUSIONS: ICD implantation can be
      performed without epicardial patches or transvenous high-energy leads in this
      population, using individualized techniques. This will allow ICD use in patients
      who have intracardiac shunting or are deemed too small for transvenous ICD leads.
      The long-term outcome and possible complications are as yet unknown in this
      population, and they should be monitored closely with follow-up DFTs.

PMID- 16426399
TI  - Nontransvenous implantable cardioverter defibrillator systems: not just for small
      pediatric patients.

PMID- 16426400
TI  - Age of first faint in patients with vasovagal syncope.
AB  - INTRODUCTION: Understanding whether vasovagal syncope is a lifelong disorder
      might shed insight into its physiology and affect management strategies.
      Accordingly, we determined the age of the first syncopal spell in adult patients
      who sought care for syncope. METHODS AND RESULTS: Patients were 42 +/- 18 years
      old with 64% women. They had had a median 8 syncope spells (interquartile range
      [IQR]: 4, 20) with a median frequency of 1.0 syncopal spells per year. The range
      of syncopal spells was 1-3,375, and the range of duration of history of syncope
      was 0.003-70 years. The first syncopal spell occurred at ages 0-81 in a skewed
      distribution, with a marked mode age of 13 years, a median age of 18 years (IQR
      12, 37), and a mean age of 26 +/- 20 years. The distributions were statistically
      indistinguishable across countries (P = 0.50), among Canadian regions (P = 0.69),
      and between the studies (P = 0.49). The same modal values were seen in males and
      females, and in patients <40 and > or =40 years old. However, patients > or =40
      years had median ages of onset older than patients <40 years (36 +/- 23 vs 17 +/-
      8 years). Patients had a recalled history of syncopal spells of median duration
      of 10 years (IQR: 2, 23), with a range of 0.003-70 years. An age of onset <44
      years was 86% accurate for vasovagal syncope. CONCLUSION: The most common age at
      which vasovagal syncope first presents is 13 years, and patients remain at risk
      of syncope for many years. Lifelong coping strategies may be desirable.

PMID- 16426401
TI  - Once a fainter, always a fainter?

PMID- 16426402
TI  - Intraoperative comparison of a subthreshold test pulse with the standard high
      energy shock approach for the measurement of defibrillation lead impedance.
AB  - There are two methods to measure shocking lead impedance: delivery of high-energy
      shocks that require patient sedation, and the painless measurement of impedance
      from subthreshold test pulses. The aim of this study was to compare the two
      methods. METHODS: The study included 131 patients implanted with a standard DR (n
      = 71) or VR (n = 60) ICD connected to either single-coil (n = 39) or dual-coil (n
      = 92) defibrillation leads. The noninvasive high-energy impedance test was done
      using a 17 J shock after induction of ventricular tachyarrhythmias and compared
      to a 0.4 microJ test pulse used by the ICD for the subthreshold measurements.
      RESULTS: Defibrillation lead impedance measurements were not significantly
      different between patients with the same shocking vector configuration. In
      patients with a single-coil defibrillation lead the impedance was 62 +/- 9 Omega
      with the high-energy shock and 62 +/- 8 Omega with the subthreshold test pulses
      (P = 0.13). Patients with a dual-coil configuration recorded average impedances
      of 40 +/- 5 Omega from both tests (P = 0.44). While there was no difference in
      values recorded within each lead configuration, there was a significant
      difference in impedance between the single-coil and the dual-coil patient groups
      (P = 0.001). CONCLUSIONS: There was no significant difference between shocking
      lead impedances measured with the high-energy shock or the subthreshold test
      pulses. This offers the possibility of noninvasive, low-energy serial
      measurements of shocking lead impedance at follow-up visits and removing the need
      for sedation.

PMID- 16426403
TI  - An outwardly rectifying chloride channel in human atrial cardiomyocytes.
AB  - INTRODUCTION: Among a range of chloride channels, outwardly rectifying Cl-
      channels have been reported in the heart of various species. Although the anionic
      current carried by this channel has been subjected to intense
      electrophysiological investigations, paradoxically no examination of single
      channel currents has been reported for human cardiomyocytes. METHODS AND RESULTS:
      Using the cell-attached and cell-free configurations of the patch-clamp
      technique, we have characterized the properties of an outwardly rectifying
      chloride current (ORCC) at the unitary level in freshly isolated human atrial
      cardiomyocytes. In excised inside-out patches, the channel presented a nonlinear
      I/V relationship with a conductance of 76.5 +/- 14.7 pS in the positive voltage
      range and 8.1 +/- 2 pS in the negative voltage range, indicating an outward
      rectification. Preincubation with the protein kinase C activator phorbol 12
      myristate 13-acetate (PMA) significantly increased the number of spontaneously
      active channels observed. The channel was Cl- selective (Cl- to Na+ permeability
      ratio, PCl/PNa= 18) with the permeability sequence I- > Br- > Cl- > F- >
      gluconate. It was blocked by the classical Cl- channels blockers glibenclamide,
      NPPB, SITS, and DIDS. Channel activity was not dependent upon internal calcium
      concentration. In the cell-attached configuration, ORCC channel activation was
      observed under perfusion of a hypotonic solution. CONCLUSION: Human atrial
      myocytes express an outwardly rectifying Cl- channel that is sensitive to PKC
      activation. This channel shares biophysical and pharmacological properties with
      the swelling-activated chloride current implicated in cardiac pathologies such as
      myocardial ischemia and dilated cardiopathies.

PMID- 16426404
TI  - Human atrial chloride channels: swelling with pride.

PMID- 16426405
TI  - Avoiding microbubbles formation during radiofrequency left atrial ablation versus
      continuous microbubbles formation and standard radiofrequency ablation protocols:
      comparison of energy profiles and chronic lesion characteristics.
AB  - BACKGROUND: Radiofrequency (RF) energy parameters and chronic lesion
      characteristics associated with the microbubbles formation have not been yet
      fully elucidated. OBJECTIVES: The objective of this study was to compare the
      energy profiles and chronic lesion characteristics associated with RF ablation of
      the pulmonary vein antrum using three different ablation protocols: (1) avoiding
      microbubbles; (2) continuous microbubble formation; (3) temperature-guided
      ablation. METHODS: A 4-mm tip ablation catheter was used for creating RF ablation
      lesions in 15 adult mongrel dogs. All ablation lesions were created at the
      posterior aspect of the PV antrum in each animal. Avoiding microbubbles (group 1,
      n = 5 dogs, 23 lesions), continuous microbubble formation (group 2, n = 5 dogs,
      22 lesions), and temperature-guided (group 3, n = 5 dogs, 19 lesions, target
      temperature 60 degrees C/power limit 50 W) ablation lesions were analyzed.
      RESULTS: Group 1 showed significantly lower power (19 +/- 8.6 W), lower
      temperature (50 +/- 4.8 degrees C), higher efficiency-of-heating index (2.9 +/-
      0.8 degrees C/W), and lower impedance (109 +/- 24.4 Omega) than groups 2 (38 +/-
      8.4 W; 63 +/- 10 degrees C; 1.8 +/- 0.8 degrees C/W; 148 +/- 34.4 Omega) and 3
      (44 +/- 12 W; 57 +/- 2.4 degrees C; 1.4 +/- 0.5 degrees C/W; 139 +/- 23.1 Omega)
      (P < 0.001 vs groups 2 and 3). During ablation, no significant events were
      detected in group 1, but 11 cases of audible pop, 11 cases of catheter tip
      charring, and 1 case of fatal myocardial perforation were observed in groups 2
      and 3. Transmural lesions were more frequently created in group 1. CONCLUSION: RF
      energy delivery applying "avoiding microbubbles" protocol seems to be associated
      with higher degree of safety and efficacy when compared to temperature-guided and
      continuous microbubble-formation ablation protocols.

PMID- 16426406
TI  - Use of ICE for RF ablation of AF.

PMID- 16426407
TI  - Comparison of radiofrequency ablation in normal versus scarred myocardium.
AB  - INTRODUCTION: Reentrant circuits causing ventricular tachycardia are closely
      associated with previously scarred myocardium. The presence of scar has been
      blamed for the poor success rate of radiofrequency ablation (RFA) in that
      context. This article investigates the in vivo effects of radiofrequency ablation
      in myocardium scarred from acute myocardial infarction. METHODS AND RESULTS:
      Anterior myocardial infarction was induced in five dogs by ligating the left
      anterior descending artery. The mean left ventricular ejection fraction after
      infarction was 38%. At a mean of 15 weeks following myocardial infarction, 50 RFA
      lesions were created in random order, 25 in scarred and 25 in normal myocardium
      using a needle electrode (21 gauge, 5 mm in length) introduced from the
      epicardium of the left ventricle at thoracotomy. During unipolar temperature
      controlled RFA (90 degrees C for 60 seconds), intramural temperatures were
      measured by thermistors at distances of 1, 2, 3, 4, and 5 mm from the ablating
      electrode. The margins of the lesions were clearly discernible in scar at
      histological examination in 64% of ablations where the scarring was patchy. There
      were no significant differences between lesion sizes, intramural temperatures at
      different distances, total energy required for ablation, or mean impedance during
      ablation of normal versus scarred myocardium. CONCLUSIONS: Scar does not affect
      lesion size or intramural temperature profile during RFA if electrode size,
      tissue contact, and tip temperature are controlled. More radiofrequency energy is
      not required to maintain tip temperature at 90 degrees C in scar compared to
      normal myocardium.

PMID- 16426408
TI  - Mechanism of repolarization alternans has restitution of action potential
      duration dependent and independent components.
AB  - INTRODUCTION: Investigation of relationship between diastolic-interval (DI)
      dependent restitution of action potential duration (APD) and alternans of APD has
      produced conflicting results. We used a novel pacing protocol to determine the
      role of restitution in alternans by minimizing changes in DI preceding each
      activation. METHODS: Transmembrane potentials were recorded from right
      ventricular endocardial tissue isolated from five dogs. We used three pacing
      sequences: (i) The tissue was paced at a constant DI for 100 beats. (ii) The DIs
      were changed randomly between two sequences of constant DI. (iii) Each constant
      DI trial was followed by constant cycle length trial where pacing cycle length
      was equal to average cycle length during previous constant DI trial. RESULTS:
      Alternans of APD occurred even when DIs preceding each activation were invariant.
      Slopes of restitution during constant DI pacing were both negative and positive
      and were much larger than unity. Alternans amplitude during constant cycle length
      pacing was larger than during constant DI, 32.2 +/- 12.3 versus 7.5 +/- 2.8 msec,
      P < 0.01. Random perturbation of DI decreased alternans amplitude during constant
      DI pacing from 14.7 +/- 4.8 to 10.5 +/- 3.4 msec, P < 0.01. CONCLUSION: Our
      results indicate that mechanism of repolarization alternans has restitution
      dependent and restitution-independent components. However, our results also
      provide direct evidence that shows that DI-dependent restitution of APD is not a
      necessary mechanism for the alternans to exist. Ability to pace with explicit
      control of DI provides a novel approach to dissect mechanisms of alternans into
      restitution-dependent and restitution-independent effects.

PMID- 16426409
TI  - Electrical alternans: membrane-limited and subcellular components.

PMID- 16426410
TI  - Monomorphic ventricular tachycardia due to Brugada syndrome successfully treated
      by hydroquinidine therapy in a 3-year-old child.
AB  - Mutations in the SCN5A gene can cause Brugada syndrome, a genetically inherited
      form of idiopathic ventricular fibrillation. We describe the case of a 3-year-old
      child with a structurally normal heart presenting with monomorphic ventricular
      tachycardia. Her electrocardiogram suggested a Brugada syndrome and the diagnosis
      was confirmed by the identification of a Brugada syndrome in her mother and in
      two other family members. Genetic study led to the identification of a c.2516T-
      >C SCN5A mutation. The child was treated with quinidine therapy without
      recurrence of arrhythmic events for a time period of 16 months.

PMID- 16426411
TI  - Acceleration-dependent left bundle branch block with severe left ventricular
      dyssynchrony results in acute heart failure: are there more patients who benefit
      from cardiac resynchronization therapy?
AB  - Cardiac resynchronization therapy (CRT) has been proposed to improve hemodynamics
      in patients with heart failure and left bundle branch block (LBBB) by
      resynchronization of left ventricular (LV) dyssynchrony. The current report
      concerns a patient with narrow QRS complex without LV dyssynchrony who
      experienced an acute exacerbation of heart failure following exercise. Careful
      analysis revealed that an increase of heart rate induced acceleration-dependent
      LBBB with severe LV dyssynchrony and mitral regurgitation followed by acute heart
      failure and hemodynamic collapse. CRT prevented these adverse reactions.
      Accordingly, optimal evaluation for CRT may include testing for LV dyssynchrony
      during exercise.

PMID- 16426412
TI  - Implantation of a biatrial pacemaker in a patient with sinus venosus atrial
      septal defect and persistent left superior vena cava.

PMID- 16426413
TI  - Visualization of the esophagus throughout left atrial catheter ablation for
      atrial fibrillation.

PMID- 16426414
TI  - A classic but uncommon principle.

PMID- 16426415
TI  - The postural tachycardia syndrome: a concise guide to diagnosis and management.

PMID- 16426416
TI  - Sudden cardiac death in patients with chagas heart disease and preserved left
      ventricular function.

PMID- 16426417
TI  - 39th Annual Conference of Physiology and Pathology of Reproduction and 31st
      Mutual Conference on Veterinary and Human Reproductive Medicine.

PMID- 16426418
TI  - Mathematical model for the cancer stem cell hypothesis.
AB  - Recent research on the origin of brain cancer has implicated a subpopulation of
      self-renewing brain cancer stem cells for malignant tumour growth. Various genes
      that regulate self-renewal in normal stem cells are also found in cancer stem
      cells. This implies that cancers can occur because of mutations in normal stem
      cells and early progenitor cells. A predictive mathematical model based on the
      cell compartment method is presented here to pose and validate non-intuitive
      scenarios proposed through the neural cancer stem cell hypothesis. The growths of
      abnormal (stem and early progenitor) cells from their normal counterparts are
      ascribed with separate mutation probabilities. Stem cell mutations are found to
      be more significant for the development of cancer than a similar mutation in the
      early progenitor cells. The model also predicts that, as previously hypothesized,
      repeated insult to mature cells increases the formation of abnormal progeny, and
      hence the risk of cancer.

PMID- 16426419
TI  - Implications of a simple mathematical model to cancer cell population dynamics.
AB  - Recent research in cancer progression and treatment indicates that many forms of
      cancer arise from the development of a small subpopulation of abnormal cancer
      stem cells (CSCs) that promote cancer growth and spread. Many potential
      treatments preferentially interact with cells at certain stages of the cell cycle
      by either selective killing or halting the cell cycle, such as intense,
      nanosecond-duration pulsed electric fields (nsPEFs). Simple mathematical models
      of unfed cancer cell populations at the plateau of their growth characteristics
      may estimate the long-term consequences of these treatments on proliferating and
      quiescent cell populations. Applying such a model with no transition from the
      quiescent to proliferating state shows that it is possible for the proliferating
      cell population to fall below 1 if the quiescent cell population obtains a
      sufficient competitive advantage with respect to nutrient consumption and/or
      survival rate. Introducing small, realistic transition rates did not appreciably
      alter short-term or long-term population behaviour, indicating that the predicted
      small cell population behaviour (< 1 cell) is not an artefact of the simpler
      model. Experimental observations of nsPEF-induced effects on the cell cycle
      suggest that such a model may serve as a first step in assessing the viability of
      a given cancer treatment in vitro prior to clinical application.

PMID- 16426420
TI  - Epstein-Barr virus-induced transformation of B cells for the diagnosis of genetic
      metabolic disorders--enumerative conditions for cryopreservation.
AB  - Epstein-Barr virus (EBV) infection in vitro causes transformation of B cells and
      generates B lymphoblastoid cell lines (LCLs). These LCLs have been widely used
      for the diagnostic of several genetic metabolic disorders. However, up to now,
      efficiency of LCL generation has been based on misleading subjective analysis. In
      this study, quantitative analyses have been performed to indicate efficiency of B
      cell transformation to measuring human lysosomal acid hydrolases associated with:
      GM1-gangliosidosis type I, Gaucher disease and mucopolysaccharidosis type I.
      Peripheral blood mononuclear cells were isolated from 13 subjects, and LCLs were
      produced by culturing them with EBV for 12 days. Activities of the enzymes beta
      galactosidase, beta-glucosidase and alpha-iduronidase were measured before and
      after cryopreservation in liquid nitrogen for 30 days. Efficiency of the B-cell
      transformation was screened every 4 days by the enumeration of cell
      proliferation, cell counts and changes in granularity estimated by flow
      cytometry. We observed the generation of 13 LCLs. Cell transformation was
      confirmed by the gradual increase of cellular clusters, cell size and
      granularity. In addition, we determined that the activity of the enzymes
      mentioned above did not change following cryopreservation. These data suggest
      that our enumerative approach for screening of EBV-LCLs is efficient for the
      enzymatic determination of human lysosomal acid hydrolases and may thus replace
      misleading subjective analyses.

PMID- 16426421
TI  - Influence of endogenous glutathione level on X-ray induced cell cycle delay in
      human lymphocytes.
AB  - Here, induction of chromosomal aberration after X-irradiation and the pattern of
      cell cycle kinetics have been investigated in human lymphocytes, after exogenous
      addition of reduced glutathione or by depleting levels of reduced glutathione
      endogenously. Involvement of cell cycle regulator proteins such as p53 and p21
      has been investigated to elucidate their role in induction of delay in cell cycle
      progression after irradiation.

PMID- 16426422
TI  - ATM activation and histone H2AX phosphorylation as indicators of DNA damage by
      DNA topoisomerase I inhibitor topotecan and during apoptosis.
AB  - Damage that engenders DNA double-strand breaks (DSBs) activates ataxia
      telangiectasia mutated (ATM) kinase through its auto- or trans-phosphorylation on
      Ser1981 and activated ATM is one of the mediators of histone H2AX phosphorylation
      on Ser139. The present study was designed to explore: (i) whether measurement of
      ATM activation combined with H2AX phosphorylation provides a more sensitive
      indicator of DSBs than each of these events alone, and (ii) to reveal possible
      involvement of ATM activation in H2AX phosphorylation during apoptosis.
      Activation of ATM and/or H2AX phosphorylation in HL-60 or Jurkat cells treated
      with topotecan (Tpt) was detected immunocytochemically in relation to cell cycle
      phase, by multiparameter cytometry. Exposure to Tpt led to concurrent
      phosphorylation of ATM and H2AX in S-phase cells, whereas G1 cells were
      unaffected. Immunofluorescence (IF) of the S-phase cells immunostained for ATM
      S1981P and gammaH2AX combined was distinctly stronger compared to that of the
      cells stained for each of these proteins alone. However, because of the
      relatively high ATM-S1981P IF of G1 cells, the ratio of IF of S to G1 cells, that
      is, the factor that determines competence of the assay in distinction of cells
      with DSBs, was 2- to 3-fold lower for ATM-S1981P alone, or for ATM-S1981P and
      gammaH2AX IF combined, than for gammaH2AX alone. ATM activation concurrent with
      H2AX phosphorylation, likely triggered by induction of DSBs during DNA
      fragmentation, occurred during apoptosis. The data suggest that frequency of
      activated ATM and phosphorylated H2AX molecules, per apoptotic cell, is
      comparable.

PMID- 16426424
TI  - When the curtain falls . . .

PMID- 16426423
TI  - Erythroid differentiation denucleation factors (EDDFs) function as intrinsic,
      post-erythropoietin regulators for mammalian erythroid terminal differentiation.
AB  - Regulatory factors other than erythropoietin (Epo) dependence, that control
      mammalian erythroid terminal differentiation, are currently uncertain. Here we
      report the existence of erythroid differentiation factors in erythroid cytoplasm.
      Purification of these factors from cultured Friend virus anaemia (FVA)-infected
      mouse splenic erythroblasts was carried out using isoelectrophoresis and high
      performance of liquid chromatography techniques. We have identified intracellular
      erythroid differentiation denucleation factors (EDDFs) that were able to mediate
      the events of post-Epo-dependent erythroblast terminal differentiation. Purified
      EDDF proteins bound specifically to the enhancer HS2 sequence of the globin gene
      activated the expression of haemoglobin in mouse erythroleukaemia and K562
      erythroleukaemic cells and promoted them to differentiate into mature
      erythrocytes. EDDF proteins began to emerge at the pro-early erythroblast stages
      upon exposure to Epo in culture, and increased dramatically in early erythroblast
      stage. The dynamic of EDDF expression and its action on the key events of
      erythroblast differentiation and denucleation appeared to be closely consistent
      with its spatiotemporal distribution. These results suggest that EDDFs are the
      critical intracellular regulatory factors that may act as the successive
      regulators to Epo, responsible for the final stages of erythroid terminal
      differentiation.

PMID- 16426425
TI  - Cultural health beliefs in a rural family practice: a Malaysian perspective.
AB  - BACKGROUND: Understanding the sociocultural dimension of a patient's health
      beliefs is critical to a successful clinical encounter. Malaysia with its multi
      ethnic population of Malay, Chinese and Indian still uses many forms of
      traditional health care in spite of a remarkably modern rural health service.
      OBJECTIVE: The objective of this paper is discuss traditional health care in the
      context of some of the cultural aspects of health beliefs, perceptions and
      practices in the different ethnic groups of the author's rural family practices.
      This helps to promote communication and cooperation between doctors and patients,
      improves clinical diagnosis and management, avoids cultural blind spots and
      unnecessary medical testing and leads to better adherence to treatment by
      patients. DISCUSSION: Includes traditional practices of 'hot and cold', notions
      of Yin-Yang and Ayurveda, cultural healing, alternative medicine, cultural
      perception of body structures and cultural practices in the context of women's
      health. Modern and traditional medical systems are potentially complementary
      rather than antagonistic. Ethnic and cultural considerations can be integrated
      further into the modern health delivery system to improve care and health
      outcomes.

PMID- 16426426
TI  - Going home from hospital: the postdischarge experience of patients and carers in
      rural and remote Queensland.
AB  - OBJECTIVE: This paper reports on a study of the experiences of patients and
      carers discharged from the Townsville General Hospital into rural and remote
      communities in North Queensland. DESIGN: The findings presented in this paper are
      drawn from post-discharge in-depth, qualitative interviews of both patients and
      carers. RESULTS: The findings indicate the importance of examining the lived
      experience of both patients and carers in attempting to understand the impact of
      current discharge practices. CONCLUSION: We conclude that carers are providing
      the bulk of post-discharge care of patients - a difficult role in which the
      difficulties are exacerbated when the patient or the carer or both is a long way
      from the home community.

PMID- 16426427
TI  - Going country: rural student placement factors associated with future rural
      employment in nursing and allied health.
AB  - OBJECTIVE: To measure the rate and predictors of health science graduates joining
      the rural health workforce following a rural placement. DESIGN: Longitudinal
      survey including the years immediately prior to and post graduation. SETTING:
      Western Australian health sciences graduates contacted by email and/or phone.
      PARTICIPANTS: Allied health and nursing students from urban campuses of three
      Western Australian universities who had taken a rural placement in their final
      year of study between 2000 and 2003. MAIN OUTCOME MEASURES: Location of
      employment six months or more after graduation. RESULTS: Of 429 participating
      allied health and nursing graduates, 25% had entered the rural workforce. Factors
      with a positive bivariate association with rural employment were: rural
      background, health discipline, self-reported value of placement, non-compulsory
      rural placement, and placements of four weeks or less. After controlling for
      rural background, the value and duration of the placement were significantly
      associated with rural employment. CONCLUSIONS: This study augments previous work
      showing that any prior rural background is a significant predictor of rural work.
      Rural practitioners of both urban and rural origin who undertake voluntary rural
      placements are more likely to enter rural practice and consequently mandatory
      placements may not be helpful to increasing the rural workforce. The quality of a
      placement is a highly significant factor associated with future workplace choice,
      the details of which need to be further investigated.

PMID- 16426429
TI  - Primary medical care workforce enumeration in rural and remote areas of
      Australia: time for a new approach?
AB  - The rural and remote primary medical workforce continues to struggle to meet
      community needs. This paper looks at the strengths and weaknesses of the various
      datasets used to measure workforce. The analysis concludes that no current data
      set adequately describes workforce from a community need perspective. In
      particular, activity based data sets based on claims data do not capture issues
      such as service mix or the importance of issues outside activity collections,
      such as time on call. The paper calls for a new approach to workforce measurement
      based on a community needs model.

PMID- 16426428
TI  - Renal disease in the Aboriginal community of Woorabinda.
AB  - OBJECTIVE: An apparent increase in the incidence of end-stage renal disease had
      been observed in the Australian Aboriginal community of Woorabinda. This study
      documents the incidence of end-stage renal disease (ESRD) in Woorabinda, and
      correlates this with predictors of renal disease. DESIGN: The methodology
      included a retrospective audit of deaths from, and cases commencing treatment for
      ESRD between 1999 and 2001 in Woorabinda, and a cross-sectional study.
      PARTICIPANTS: The 183 participants were Aboriginal residents over 15 years of
      age. Females numbered 102 (55.7%) and males 81 (44.3%). MAIN OUTCOME MEASURE: The
      incidence of ESRD was comparable to other recognised high incidence Indigenous
      communities in Australia. This was corroborated by a high prevalence of
      predictors of renal disease. RESULTS: Audit: the year 2001 age- and sex
      standardised incidence ratio for commencement of renal replacement therapy is
      93.18 (95% CI, 25.34-238.53). Clinical Study: the prevalence of overt albuminuria
      was 7.6%; 11.7% had an albumin : creatinine ratio >3.4-33.9 g mol(-1); 33.3% had
      microalbuminuria of > or =20 mg L(-1); and 67.8% prevalence of proteinuria was
      found. The prevalence of diabetes was 18.6%, with another 13.2% having impaired
      fasting glucose. There was a 19.7% prevalence of hypertension. Of those with
      hypertension 22.2% had overt albuminuria. CONCLUSIONS: Although Woorabinda was
      previously placed in a region of low end-stage renal disease incidence, further
      investigation has identified a high incidence of renal disease, not exclusively
      due to diabetes. The finding raises questions regarding the current trajectory of
      the epidemic in other Aboriginal and Torres Strait Islander communities.

PMID- 16426430
TI  - Collaboration and referral practices of general practitioners and community
      mental health workers in rural and remote Australia.
AB  - OBJECTIVE: To assess an important part of Australia's National Mental Health
      Strategy by examining the collaboration and referral practices between general
      practitioners and community mental health workers in rural and remote areas.
      DESIGN: Semistructured interviews. SETTING: Rural and remote health service
      region in Australia. PARTICIPANTS: In total, 31 general practitioners and 14
      mental health workers. RESULTS: Meaningful collaboration and referral practices
      between general practitioners and mental health workers are prevented by
      contradictory and ambiguous definitions involving professional roles and mental
      health. A pattern of negative collaboration was further magnified by the rural
      and remote context. CONCLUSION: The implementation of Australia's National Mental
      Health Strategy faces serious problems in rural and remote area due to the
      negative collaboration and referral practices between general practitioners and
      mental health workers.

PMID- 16426432
TI  - Rural health professionals' use of a clinical information web site in Western
      Australia.

PMID- 16426431
TI  - What do we mean by sustainable rural health services? Implications for rural
      health research.
AB  - The concept of health service sustainability, endorsed by the Australian Health
      Ministers as a key dimension of the National Performance Framework, is
      particularly important in rural and remote communities. To date, however, few
      Australian studies have demonstrated how the real drivers of sustainability inter
      relate or are translated into sustainable rural and remote health services. This
      article highlights the need for a systemic approach in which the integrated
      nature of sustainability components are recognised and evaluated in terms of
      access to rural and remote health services, quality of care and cost of
      provision.

PMID- 16426433
TI  - Comparing rural and urban school canteens: a snapshot.

PMID- 16426434
TI  - Driving tired: cultural factors, long-distance driving and fatigue.

PMID- 16426439
TI  - Raising government's awareness of rural nurses: their role and contribution to
      the health workforce.

PMID- 16426435
TI  - Doctor Robert Benjamin Cooter AM, MB BS, FRACGP, FAMA.

PMID- 16426440
TI  - A quantitative linkage score for an association study following a linkage
      analysis.
AB  - BACKGROUND: Currently, a commonly used strategy for mapping complex quantitative
      traits is to use a genome-wide linkage analysis to narrow suspected genes to
      regions on a scale of centiMorgans (cM), followed by an association analysis to
      fine map the genetic variation in regions showing linkage. Two important
      questions arise in the design and the resulting inference at the association
      stage of this sequential procedure: (1) how should we design an efficient
      association study given the information provided by the previous linkage study?
      and (2) can an association in a linkage region explain, in part, the detected
      linkage signal? RESULTS: We derive a quantitative linkage score (QLS) based on
      Haseman-Elston regression (Haseman and Elston 1972) and make use of this score to
      address both questions. In designing an association study, the selection of a
      subsample from the linkage study sample can be guided by the linkage information
      summarized in the QLS. When heterogeneity exists, we show that selection based on
      the QLS can increase the proportion of sample individuals from the subpopulation
      affected by a disease allele and therefore greatly improves the power of the
      association study. For the resulting inference, we frame as a hypothesis test the
      question of whether a linkage signal in a region can be in part explained by a
      marker allele. A simple one sided paired t-statistic is defined by comparing the
      two sets of QLSs obtained with/without modeling a marker association: a
      significant difference indicates that the marker can at least partly account for
      the detected linkage. We also show that this statistic can be used to detect a
      spurious association. CONCLUSION: All our results suggest that a careful
      examination of QLSs should be helpful for understanding the results of both
      association and linkage studies.

PMID- 16426442
TI  - The influence of the pituitary tumor transforming gene-1 (PTTG-1) on survival of
      patients with small cell lung cancer and non-small cell lung cancer.
AB  - BACKGROUND: PTTG-1 (pituitary tumor transforming gene) is a novel oncogene that
      is overexpressed in tumors, such as pituitary adenoma, breast and
      gastrointestinal cancers as well as in leukemia. In this study, we examined the
      role of PTTG-1 expression in lung cancer with regard to histological subtype, the
      correlation of PTTG-1 to clinical parameters and relation on patients' survival.
      METHODS: Expression of PTTG-1 was examined immunohistochemically on formalin
      fixed, paraffin-embedded tissue sections of 136 patients with small cell lung
      cancer (SCLC) and 91 patients with non-small cell lung cancer (NSCLC),
      retrospectively. The intensity of PTTG-1 expression as well as the proportion of
      PTTG-1 positive cells within a tumor was used for univariate and multivariate
      analysis. RESULTS: PTTG-1 expression was observed in 64% of SCLC tumors and in
      97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression
      was associated with a shorter mean survival time compared with patients with
      strong PTTG-1 expression (265 +/- 18 days vs. 379 +/- 66 days; p = 0.0291). Using
      the Cox regression model for multivariate analysis, PTTG-1 expression was a
      significant predictor for survival next to performance status, tumor stage, LDH
      and hemoglobin. In contrast, in patients with NSCLC an inverse correlation
      between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was
      associated with a shorter mean survival of 306 +/- 58 days compared with 463 +/-
      55 days for those patients with no or low PTTG-1 intensities (p = 0.0386).
      Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype
      with an advanced pathological stage, extensive lymph node metastases, distant
      metastases and increased LDH level. Multivariate analysis using Cox regression
      confirmed the prognostic relevance of PTTG-1 expression next to performance
      status and tumor stage in patients with NSCLC. CONCLUSION: Lung cancers belong to
      the group of tumors expressing PTTG-1. Dependent on the histological subtype of
      lung cancer, PTTG-1 expression was associated with a better outcome in patients
      with SCLC and a rather unfavourable outcome for patients with NSCLCs. These
      results may reflect the varying role of PTTG-1 in the pathophysiology of the
      different histological subtypes of lung cancer.

PMID- 16426441
TI  - Wnt signaling induces epithelial differentiation during cutaneous wound healing.
AB  - BACKGROUND: Cutaneous wound repair in adult mammals does not regenerate the
      original epithelial architecture and results in altered skin function. We propose
      that lack of regeneration may be due to the absence of appropriate molecular
      signals to promote regeneration. In this study, we investigated the regulation of
      Wnt signaling during cutaneous wound healing and the consequence of activating
      either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on
      epidermal architecture during wound repair. RESULTS: We determined that the
      expression of Wnt ligands that typically signal via the beta-catenin-independent
      pathway is up-regulated in the wound while the beta-catenin-dependent Wnt
      signaling is activated in the hair follicles adjacent to the wound edge. Ectopic
      activation of beta-catenin-dependent Wnt signaling with lithium chloride in the
      wound resulted in epithelial cysts and occasional rudimentary hair follicle
      structures within the epidermis. In contrast, forced expression of Wnt-5a in the
      deeper wound induced changes in the interfollicular epithelium mimicking
      regeneration, including formation of epithelia-lined cysts in the wound dermis,
      rudimentary hair follicles and sebaceous glands, without formation of tumors.
      CONCLUSION: These findings suggest that adult interfollicular epithelium is
      capable of responding to Wnt morphogenic signals necessary for restoring
      epithelial tissue patterning in the skin during wound repair.

PMID- 16426443
TI  - Cyclin D1 and Rb protein expression and their correlation with prognosis in
      patients with colon cancer.
AB  - BACKGROUND: Cyclin D1 plays a major role as a potential contributor to the
      multistep process of oncogenesis; nevertheless its prognostic significance in
      colon cancer has already been examined in a few studies and needs to be further
      delineated. The aim of this study was to assess the expression of cyclin D1 and
      pRb and to correlate them with tumor histological stage and grade, proliferative
      capacity (Ki-67 labeling index) and clinical parameters, in order to delineate
      their impact on prognosis. METHODS: One hundred and eleven patients, who
      underwent surgical resection of the colon for colon cancer constituted the group
      of our study. The immunohistochemical expression of cyclin D1, Rb and Ki-67
      proteins was examined and correlated with clinico-pathological parameters and
      survival. RESULTS: The 5-years survival rate of patients presenting cyclin D1
      positive tumors was 54%, while that of cyclin D1 negative ones was 67% (P = or >
      0.05). The survival rate of patients with pRb positive tumors was similar to that
      of pRb negative ones. Significant association was observed between Ki-67 and
      cyclin D1 positivity (P = 0.045). Univariate analysis revealed worse survival in
      advanced stage patients presenting cyclin D1 positive tumors (P = 0.025).
      Additionally, the survival of patients aging less than 70 years old was
      correlated to cyclin D1 positivity (P = 0.009). Multivariate survival analysis
      revealed statistical significance for stage and hepatic metastasis. CONCLUSION:
      Even though cyclin D1 and pRb have not disclosed any clear association with
      shorter survival, cyclin D1 positivity may be a useful predictor of subgroup
      patients with colon cancer being in advanced stage and early age.

PMID- 16426444
TI  - How useful are post consultation letters to patients?
AB  - BACKGROUND: As part of the NHS plan it was suggested that all patients receive
      copies of letters sent to their General Practitioner following outpatient
      consultations. The former Secretary of State for Health extended this proposal,
      suggesting that patients have a specific letter to themselves after a hospital
      consultation. METHODS: The aim of this study was to send cardiorespiratory
      patients attending Charing Cross Hospital, a copy of the letter sent to their
      G.P. plus a specific letter to themselves and to assess the usefulness and
      comprehensibility of each. The letters were analysed for dictation time, Flesch
      Reading Ease Score, Flesch-Kincaid Grade Level and word count. Eighty-four out of
      105 sequential patients (80%) consented and were sent both types of letter after
      their attendance. Patients returned both letters circling any items they did not
      understand and stated a preference for the GP letter, patient letter, or both.
      The patients' GPs were subsequently also asked for their views on each letter.
      RESULTS: GP letters took significantly longer to dictate than patient letters.
      The Flesch Reading Ease Score was significantly higher in the patient letters,
      indicating that the patient letters were easier to read. The GP letters were
      significantly longer than the patient letters and patients were significantly
      more likely to circle more items in the GP letters (p < 0.001). The content of
      letters is sometimes inaccurate. Thirty-six out of 62 patients (58%) would like
      to receive both letters, 13/62 (21.6%) would prefer the GP letter and 13/62 (20%)
      wanted only the patient letter. 45 GPs replied (62.5%), 28/45 (62.5%) wanted the
      GP letter, 14 GPs (31.1%) wanted both letters and 3/45 (6.7%) wanted the patient
      letter only. General themes concerned insufficient clinical details and the GPs
      preferred the structure of the letters written to them. CONCLUSION: Patients
      appreciate copies of the letter being sent to their GP but comprehension is less
      good than with a shorter letter written especially to the patient. More attention
      needs to be paid to making letters to GPs simpler to read without losing the
      structure and detail liked by GPs. A compromise might be to dictate the letter in
      front of the patient and to provide a speciality-specific glossary to accompany
      each letter.

PMID- 16426445
TI  - Bloodstream and endovascular infections due to Abiotrophia defectiva and
      Granulicatella species.
AB  - BACKGROUND: Abiotrophia and Granulicatella species, previously referred to as
      nutritionally variant streptococci (NVS), are significant causative agents of
      endocarditis and bacteraemia. In this study, we reviewed the clinical
      manifestations of infections due to A. defectiva and Granulicatella species that
      occurred at our institution between 1998 and 2004. METHODS: The analysis included
      all strains of NVS that were isolated from blood cultures or vascular graft
      specimens. All strains were identified by 16S rRNA sequence analysis. Patients'
      medical charts were reviewed for each case of infection. RESULTS: Eleven strains
      of NVS were isolated during the 6-year period. Identification of the strains by
      16S rRNA showed 2 genogroups: Abiotrophia defectiva (3) and Granulicatella
      adiacens (6) or "para-adiacens" (2). The three A. defectiva strains were isolated
      from immunocompetent patients with endovascular infections, whereas 7 of 8
      Granulicatella spp. strains were isolated from immunosuppressed patients, mainly
      febrile neutropenic patients. We report the first case of "G. para-adiacens"
      bacteraemia in the setting of febrile neutropenia. CONCLUSION: We propose that
      Granulicatella spp. be considered as a possible agent of bacteraemia in
      neutropenic patients.

PMID- 16426446
TI  - Decision tools in health care: focus on the problem, not the solution.
AB  - BACKGROUND: Systematic reviews or randomised-controlled trials usually help to
      establish the effectiveness of drugs and other health technologies, but are
      rarely sufficient by themselves to ensure actual clinical use of the technology.
      The process from innovation to routine clinical use is complex. Numerous
      computerised decision support systems (DSS) have been developed, but many fail to
      be taken up into actual use. Some developers construct technologically advanced
      systems with little relevance to the real world. Others did not determine whether
      a clinical need exists. With NHS investing 5 billion pounds sterling in computer
      systems, also occurring in other countries, there is an urgent need to shift from
      a technology-driven approach to one that identifies and employs the most cost
      effective method to manage knowledge, regardless of the technology. The generic
      term, 'decision tool' (DT), is therefore suggested to demonstrate that these
      aids, which seem different technically, are conceptually the same from a clinical
      viewpoint. DISCUSSION: Many computerised DSSs failed for various reasons, for
      example, they were not based on best available knowledge; there was insufficient
      emphasis on their need for high quality clinical data; their development was
      technology-led; or evaluation methods were misapplied. We argue that DSSs and
      other computer-based, paper-based and even mechanical decision aids are members
      of a wider family of decision tools. A DT is an active knowledge resource that
      uses patient data to generate case specific advice, which supports decision
      making about individual patients by health professionals, the patients themselves
      or others concerned about them. The identification of DTs as a consistent and
      important category of health technology should encourage the sharing of lessons
      between DT developers and users and reduce the frequency of decision tool
      projects focusing only on technology. The focus of evaluation should become more
      clinical, with the impact of computer-based DTs being evaluated against other
      computer, paper- or mechanical tools, to identify the most cost effective tool
      for each clinical problem. SUMMARY: We suggested the generic term 'decision tool'
      to demonstrate that decision-making aids, such as computerised DSSs, paper
      algorithms, and reminders are conceptually the same, so the methods to evaluate
      them should be the same.

PMID- 16426447
TI  - Microsatellite instability analysis in hereditary non-polyposis colon cancer
      using the Bethesda consensus panel of microsatellite markers in the absence of
      proband normal tissue.
AB  - BACKGROUND: Hereditary non-polyposis colon cancer (HNPCC) is an autosomal
      dominant syndrome predisposing to the early development of various cancers
      including those of colon, rectum, endometrium, ovarium, small bowel, stomach and
      urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair
      genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic
      counseling of three first-degree relatives (the mother and two sisters) of a male
      who died of colorectal adenocarcinoma at the age of 23. The family fulfilled
      strict Amsterdam-I criteria (AC-I) with the presence of extracolonic tumors in
      the extended pedigree. We overcame the difficulty of having a proband post-mortem
      non-tumor tissue sample for MSI testing by studying the alleles carried by his
      progenitors. METHODS: Tumor MSI testing is described as initial screening in both
      primary and metastasis tumor tissue blocks, using the reference panel of 5
      microsatellite markers standardized by the National Cancer Institute (NCI) for
      the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250). Subsequent
      mutation analysis of the hMLH1 and hMSH2 genes was performed. RESULTS: Three of
      five microsatellite markers (BAT-25, BAT-26 and D5S346) presented different
      alleles in the proband's tumor as compared to those inherited from his parents.
      The tumor was classified as high frequency microsatellite instability (MSI-H). We
      identified in the HNPCC family a novel germline missense (c.1864C>A) mutation in
      exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr) amino
      acid substitution. CONCLUSION: This approach allowed us to establish the tumor
      MSI status using the NCI recommended panel in the absence of proband's non-tumor
      tissue and before sequencing the obligate carrier. According to the Human Gene
      Mutation Database (HGMD) and the International Society for Gastrointestinal
      Hereditary Tumors (InSiGHT) Database this is the first report of this mutation.

PMID- 16426450
TI  - Effects of mothers' socio-economic status on the management of febrile conditions
      in their under five children in a resource limited setting.
AB  - BACKGROUND: Public health research is shifting focus to the role of socioeconomic
      indicators in the promotion of health. As such an understanding of the roles that
      socio-economic factors play in improving health and health-seeking behaviour is
      important for public health policy. This is because the share of resources
      devoted to different policy options should depend on their relative
      effectiveness. OBJECTIVE: To measure the effect of socio-economic status (age,
      education, occupation, income, religion and family structure) of mothers on the
      management of febrile conditions in under-fives children. METHOD: Two hundred
      mothers who brought their febrile under-five children to a health facility were
      interviewed on the treatment they gave to their children before reporting at
      health facility. Data collected were entered and analyzed using the SPSS
      software. Binary logistic regression was adopted for the quantitative analysis of
      the effect of socio-economic variables on the mothers' actions prior to utilizing
      the health facility. RESULTS: Results showed that while mothers' age was
      negatively correlated (-0.13), occupation was positively correlated (0.17) with
      under-fives mothers' action. Education, religion, income and family structure
      were however insignificant at 5% level. CONCLUSION: This poses a lot of
      challenges to policy makers in the developing nations where women's education and
      earning capacity is low. There is therefore a need to increase the number of
      women benefiting from micro credit. This will ensure that more women are engaged
      in a form of occupation that is profitable and can sustain the economic and
      health needs of the family.

PMID- 16426448
TI  - Serum antibodies from Parkinson's disease patients react with neuronal membrane
      proteins from a mouse dopaminergic cell line and affect its dopamine expression.
AB  - Evidence exists suggesting that the immune system may contribute to the severity
      of idiopathic Parkinson's disease (IPD). The data presented here demonstrates
      that antibodies in the sera of patients with IPD have increased binding affinity
      to dopaminergic (DA) neuronal (MN9D cell line) membrane antigens in comparison to
      antibodies in sera from healthy controls. In general, the degree of antibody
      reactivity to these antigens of the mouse MN9D cell line appears to correlate
      well with the disease severity of the IPD patients contributing sera, based on
      the total UPDRS scores. Surprisingly, the sera from IPD patients enhanced the DA
      content of MN9D cells differentiated with n-butyrate; the n-butyrate
      differentiated MN9D cells had a greater concentration of DA (DA/mg total protein)
      than undifferentiated MN9D cells, especially early in culture. Although the IPD
      sera did not directly harm MN9D cellular viability or DA production, in the
      presence of the N9 microglial cell line, the amount of DA present in cultures of
      untreated or n-butyrate-treated MN9D cells was lowered by the IPD sera. The
      results suggest the involvement of antibodies in the decline of dopamine
      production and, thus, the potential of immune system participation in IPD.

PMID- 16426449
TI  - Active rehabilitation for chronic low back pain: cognitive-behavioral, physical,
      or both? First direct post-treatment results from a randomized controlled trial
      [ISRCTN22714229].
AB  - BACKGROUND: The treatment of non-specific chronic low back pain is often based on
      three different models regarding the development and maintenance of pain and
      especially functional limitations: the deconditioning model, the cognitive
      behavioral model and the biopsychosocial model. There is evidence that
      rehabilitation of patients with chronic low back pain is more effective than no
      treatment, but information is lacking about the differential effectiveness of
      different kinds of rehabilitation. A direct comparison of a physical, a cognitive
      behavioral treatment and a combination of both has never been carried out so far.
      METHODS: The effectiveness of active physical, cognitive-behavioral and combined
      treatment for chronic non-specific low back pain compared with a waiting list
      control group was determined by performing a randomized controlled trial in three
      rehabilitation centers. Two hundred and twenty three patients were randomized,
      using concealed block randomization to one of the following treatments, which
      they attended three times a week for 10 weeks: Active Physical Treatment (APT),
      Cognitive-Behavioral Treatment (CBT), Combined Treatment of APT and CBT (CT), or
      Waiting List (WL). The outcome variables were self-reported functional
      limitations, patient's main complaints, pain, mood, self-rated treatment
      effectiveness, treatment satisfaction and physical performance including walking,
      standing up, reaching forward, stair climbing and lifting. Assessments were
      carried out by blinded research assistants at baseline and immediately post
      treatment. The data were analyzed using the intention-to-treat principle.
      RESULTS: For 212 patients, data were available for analysis. After treatment,
      significant reductions were observed in functional limitations, patient's main
      complaints and pain intensity for all three active treatments compared to the WL.
      Also, the self-rated treatment effectiveness and satisfaction appeared to be
      higher in the three active treatments. Several physical performance tasks
      improved in APT and CT but not in CBT. No clinically relevant differences were
      found between the CT and APT, or between CT and CBT. CONCLUSION: All three active
      treatments were effective in comparison to no treatment, but no clinically
      relevant differences between the combined and the single component treatments
      were found.

PMID- 16426451
TI  - Concurrent crack and powder cocaine users from Sao Paulo: do they represent a
      different group?
AB  - BACKGROUND: Cocaine abuse is a serious and socially damaging illegal drug
      problem. Different routes of administration are associated with a specific
      progression of use, different degrees of abuse liability, propensity for
      dependence and treatment response. There have been relatively few studies
      comparing different cocaine users groups and no studies into the characterization
      of the group of individuals reporting concurrent use of powder cocaine and crack
      cocaine. METHODS: Six hundred and ninety-nine cocaine users were assessed during
      the period August 1997 to October 1998 in one outpatient and six inpatient
      clinics located in the Sao Paulo, Brazil. Patients were interviewed using a
      structured questionnaire schedule in Portuguese, designed specifically for the
      Brazilian population. The statistical analyses were performed using either ANOVA
      or a chi-squared test and focusing on their preferred form of use/route of
      administration and other variables. RESULTS: For 83% of the variables tested in
      this study, the Dual Users subgroup (using both powder and crack cocaine)
      demonstrated statistical differences from the single drug user subgroups. Those
      differences include the initiation of cocaine, the abuse of other illicit drugs,
      and rates of criminal history. CONCLUSION: These data suggest cocaine-dependent
      individuals who report use of both powder and crack cocaine are an at least
      partially, distinct subgroup. However, further studies will be necessary to
      confirm this and to determine if they also show a different treatment response.

PMID- 16426452
TI  - Left ventricular geometric patterns in newly presenting Nigerian hypertensives:
      an echocardiographic study.
AB  - BACKGROUND: Hypertension is a global problem and it is prevalent in Nigeria. Left
      ventricular hypertrophy is a major complication of hypertension with risk of
      sudden death and arrhythmias among others. Abnormal left ventricular geometric
      patterns also increase the burden of morbidity and mortality. It is therefore
      important to know the different left ventricular geometric patterns in Nigerian
      hypertensives because of their prognostic significance. METHODS: One hundred
      (100) newly presenting hypertensives (53 males and 47 females) and 100 controls
      (53 males and 47 females) were recruited for the study. All were subjected to
      clinical evaluation and full echocardiographic examination was performed
      according to the ASE recommendation. The relative wall thickness and the presence
      or absence of echocardiographic left ventricular hypertrophy were used to
      determine the various geometric patterns. RESULTS: The mean age of the
      hypertensive subjects was 56.06 (+/- 7.68) years while that of the control
      subjects was 56.10 (+/- 7.68) years. There was no significant difference in the
      mean ages of the two groups. In the hypertensive subjects 28% had normal
      geometry, 26% had concentric remodeling, 28% had concentric hypertrophy and 18%
      had eccentric hypertrophy. In the control group, 86% had normal geometry, 11% had
      concentric remodeling, 3% had eccentric hypertrophy and none had concentric
      hypertrophy. There was statistical significance when the geometric patterns of
      the hypertensive and controls were compared (chi2 = 74.30, p value < 0.0001).
      CONCLUSION: The study showed that only 28% of the hypertensive subjects had
      normal LV geometric pattern while 86% of the normal subjects had normal geometry.
      There is need for longitudinal studies in order to prognosticate the various
      geometric patterns.

PMID- 16426453
TI  - Developing a realistic sexual network model of chlamydia transmission in Britain.
AB  - BACKGROUND: A national chlamydia screening programme is currently being rolled
      out in the UK and other countries. However, much of the epidemiology remains
      poorly understood. In this paper we present a stochastic, individual based,
      dynamic sexual network model of chlamydia transmission and its parameterisation.
      Mathematical models provide a theoretical framework for understanding the key
      epidemiological features of chlamydia: sexual behaviour, health care seeking and
      transmission dynamics. RESULTS: The model parameters were estimated either
      directly or by systematic fitting to a variety of appropriate data sources. The
      fitted model was representative of sexual behaviour, chlamydia epidemiology and
      health care use in England. We were able to recapture the observed age
      distribution of chlamydia prevalence. CONCLUSION: Estimating parameters for
      models of sexual behaviour and transmission of chlamydia is complex. Most of the
      parameter values are highly correlated, highly variable and there is little
      empirical evidence to inform estimates. We used a novel approach to estimate the
      rate of active treatment seeking, by combining data sources, which improved the
      credibility of the model results. The model structure is flexible and is broadly
      applicable to other developed world settings and provides a practical tool for
      public health decision makers.

PMID- 16426454
TI  - Absorption and metabolism of conjugated alpha-linolenic acid given as free fatty
      acids or triacylglycerols in rats.
AB  - BACKGROUND: Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty
      acids which have been extensively studied in the past two decades. However,
      conjugated octadecatrienoic acid such as cis-9,trans-11,cis-15 and cis-9,trans
      13,cis-15, recently identified, have not been extensively investigated. This work
      presents bioavailability and tissue incorporation of a mixture of conjugated
      octadecatrienoic (CLnA) acids ingested as free fatty acids (FFA) and
      triacylglycerols (TAG). RESULTS: Male Wistar rats were fed rumenic acid (RA: cis
      9,trans-11 18:2) and a CLnA mixture (cis-9,trans-11,cis-15 18:3 and cis-9,trans
      13,cis-15 18:3) as FFA and TAG for 8 days. RA and CLnA were both totally absorbed
      when given as FFA as well as TAG. Both isomers of CLnA as FFA or TAG were
      incorporated into neutral lipids. Metabolites up to 22:6 conjugated isomers were
      present in liver and plasma phospholipids of rats fed the CLnA diets. CONCLUSION:
      Finally, CLnA are as well absorbed as RA in vivo and their incorporation into
      tissues and bioconversion are similar when ingested as FFA or as TAG.

PMID- 16426455
TI  - Emergency pulpotomy in relieving acute dental pain among Tanzanian patients.
AB  - BACKGROUND: In Tanzania, oral health services are mostly in the form of dental
      extractions aimed at alleviating acute dental pain. Conservative methods of
      alleviating acute dental pain are virtually non-existent. Therefore, it was the
      aim of this study to determine treatment success of emergency pulpotomy in
      relieving acute dental pain. METHODS:  SETTING: School of Dentistry, Muhimbili
      National Hospital, Dar es Salaam, Tanzania. STUDY DESIGN: Longitudinal study.
      PARTICIPANTS: 180 patients who presented with dental pain due to acute
      irreversible pulpitis during the study period between July and August 2001.
      Treatment and evaluation: Patients were treated by emergency pulpotomy on
      permanent posterior teeth and were evaluated for pain after one, three and six
      week's post-treatment. Pain, if present, was categorised as either mild or acute.
      RESULTS: Of the patients with treated premolars, 25 (13.9%) patients did not
      experience pain at all while 19 (10.6%) experienced mild pain. None of the
      patients with treated premolars experienced acute pain. Among 136 patients with
      treated molars 56 (31%) did not experience any pain, 76 (42.2%) experienced mild
      pain and the other 4 (2.2%) suffered acute pain. CONCLUSION: The short term
      treatment success of emergency pulpotomy was high being 100% for premolars and
      97.1% for molars, suggesting that it can be recommended as a measure to alleviate
      acute dental pain while other conservative treatment options are being
      considered.

PMID- 16426457
TI  - Changes in pharyngeal aerobic microflora in oral breathers after palatal rapid
      expansion.
AB  - BACKGROUND: The purpose of this study was to investigate in oral breathing
      children the qualitative and quantitative effects on aerobic and facultatively
      anaerobic oropharyngeal microflora of respiratory function improved by rapid
      palatal expansion (RPE). METHODS: In an open clinical trial, we studied 50 oral
      breathers, aged 8 to 14 years and suffering from both maxillary constriction and
      posterior cross-bite. At baseline, patients were examined by a single
      otorhinolaryngologist (ENT), confirming nasal obstruction in all subjects by
      posterior rhino-manometric test. Patients were evaluated three times by
      oropharyngeal swabs:1) at baseline (T = 0); 2) after palatal spreading out (T =
      1); and 3) at the end of RPE treatment (T = 2). With regard to the
      microbiological aspect, the most common and potentially pathogenic oral
      microrganisms (i.e. Streptococcus pyogenes, Diplococcus pneumoniae,
      Staphylococcus aureus, Haemophilus spp, Branhamella catarrhalis, Klebsiella
      pneumoniae, Candida albicans) were specifically detected in proper culture
      plates, isolated colonies were identified by means of biochemical tests and
      counted by calibrated loop. The data were analyzed by means of the following
      tests: Chi-square test, Fisher's exact test and Wilcoxon's test. RESULTS: After
      the use of RME there was a statistically significant decrease of Staphylococcus
      aureus stock at CFU/mLat T1(P = 0.0005; Z = -3,455 by Wilcoxon Rank test) and T2
      (P < 0.0001; Z = -4,512 by Wilcoxon Rank test) vs T0. No significant changes were
      found for the other examined microrganisms. CONCLUSION: Our data suggest that RPE
      therapy in oral breathers may strongly reduce the pathogenic aerobic and
      facultatively anaerobic microflora in the oral pharynx after a normalization of
      the upper airways function, and may reduce the risk of respiratory infections.

PMID- 16426456
TI  - Modeling the bound conformation of Pemphigus vulgaris-associated peptides to MHC
      Class II DR and DQ alleles.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a severe autoimmune blistering disorder
      characterized by the presence of pathogenic autoantibodies directed against
      desmoglein-3 (Dsg3), involving specific DR4 and DR6 alleles in Caucasians and DQ5
      allele in Asians. The development of sequence-based predictive algorithms to
      identify potential Dsg3 epitopes has encountered limited success due to the
      paucity of PV-associated allele-specific peptides as training data. RESULTS: In
      this work we constructed atomic models of ten PV associated, non-associated and
      protective alleles. Nine previously identified stimulatory Dsg3 peptides, Dsg3 96
      112, Dsg3 191-205, Dsg3 206-220, Dsg3 252-266, Dsg3 342-356, Dsg3 380-394, Dsg3
      763-777, Dsg3 810-824 and Dsg3 963-977, were docked into the binding groove of
      each model to analyze the structural aspects of allele-specific binding.
      CONCLUSION: Our docking simulations are entirely consistent with functional data
      obtained from in vitro competitive binding assays and T cell proliferation
      studies in DR4 and DR6 PV patients. Our findings ascertain that DRB1*0402 plays a
      crucial role in the selection of specific self-peptides in DR4 PV. DRB1*0402 and
      DQB1*0503 do not necessarily share the same core residues, indicating that both
      alleles may have different binding specificities. In addition, our results lend
      credence to the hypothesis that the alleles DQB1*0201 and *0202 play a protective
      role by binding Dsg3 peptides with greater affinity than the susceptible alleles,
      allowing for efficient deletion of autoreactive T cells.

PMID- 16426459
TI  - Exploring if day and time of admission is associated with average length of stay
      among inpatients from a tertiary hospital in Singapore: an analytic study based
      on routine admission data.
AB  - BACKGROUND: It has been postulated that patients admitted on weekends or after
      office hours may experience delays in clinical management and consequently have
      longer length of stay (LOS). We investigated if day and time of admission is
      associated with LOS in Tan Tock Seng Hospital (TTSH), a 1,400 bed acute care
      tertiary hospital serving the central and northern regions of Singapore. METHODS:
      This was a historical cohort study based on all admissions from TTSH from 1st
      September 2003 to 31st August 2004. Data was extracted from routinely available
      computerized hospital information systems for analysis by episode of care. LOS
      for each episode of care was log-transformed before analysis, and a multivariate
      linear regression model was used to study if sex, age group, type of admission,
      admission source, day of week admitted, admission on a public holiday or eve of
      public holiday, admission on a weekend and admission time were associated with an
      increased LOS. RESULTS: In the multivariate analysis, sex, age group, type of
      admission, source of admission, admission on the eve of public holiday and
      weekends and time of day admitted were independently and significantly associated
      with LOS. Patients admitted on Friday, Saturday or Sunday stayed on average 0.3
      days longer than those admitted on weekdays, after adjusting for potential
      confounders; those admitted on the eve of public holidays, and those admitted in
      the afternoons and after office hours also had a longer LOS (differences of 0.71,
      1.14 and 0.65 days respectively). CONCLUSION: Cases admitted over a weekend, eve
      of holiday, in the afternoons, and after office hours, do have an increased LOS.
      Further research is needed to identify processes contributing to the above
      phenomenon.

PMID- 16426458
TI  - LocustDB: a relational database for the transcriptome and biology of the
      migratory locust (Locusta migratoria).
AB  - BACKGROUND: The migratory locust (Locusta migratoria) is an orthopteran pest and
      a representative member of hemimetabolous insects for biological studies. Its
      transcriptomic data provide invaluable information for molecular entomology and
      pave a way for the comparative research of other medically, agronomically, and
      ecologically relevant insects. We developed the first transcriptomic database of
      the locust (LocustDB), building necessary infrastructures to integrate, organize,
      and retrieve data that are either currently available or to be acquired in the
      future. DESCRIPTION: LocustDB currently hosts 45,474 high-quality EST sequences
      from the locust, which were assembled into 12,161 unigenes. It, through user
      friendly web interfaces, allows investigators to freely access sequence data,
      including homologous/orthologous sequences, functional annotations, and pathway
      analysis, based on conserved orthologous groups (COG), gene ontology (GO),
      protein domain (InterPro), and functional pathways (KEGG). It also provides
      information from comparative analysis based on data from the migratory locust and
      five other invertebrate species, including the silkworm, the honeybee, the
      fruitfly, the mosquito and the nematode. The website address of LocustDB is
      http://locustdb.genomics.org.cn/. CONCLUSION: LocustDB starts with the first
      transcriptome information for an orthopteran and hemimetabolous insect and will
      be extended to provide a framework for incorporating in-coming genomic data of
      relevant insect groups and a workbench for cross-species comparative studies.

PMID- 16426460
TI  - RCAS-RNAi: a loss-of-function method for the developing chick retina.
AB  - BACKGROUND: The embryonic chick provides an excellent model system for studies of
      development. However, it has lacked an efficient loss-of-function method for
      studies of gene function. RESULTS: We show that avian retroviruses can deliver
      hairpins mediating RNA interference to the developing chick eye. These viruses
      'knock down' specific genes in infected areas of the retina. The knock down
      persists as the retina matures and can be detected using in situ hybridization.
      Furthermore, the amount of retinal tissue affected can be controlled by
      manipulating the degree of infection. CONCLUSION: This technique provides a rapid
      and efficient loss-of-function option for studies in the developing chick retina.

PMID- 16426461
TI  - Cellular transfer and AFM imaging of cancer cells using Bioimprint.
AB  - A technique for permanently capturing a replica impression of biological cells
      has been developed to facilitate analysis using nanometer resolution imaging
      tools, namely the atomic force microscope (AFM). The method, termed Bioimprint,
      creates a permanent cell 'footprint' in a non-biohazardous Poly
      (dimethylsiloxane) (PDMS) polymer composite. The transfer of nanometer scale
      biological information is presented as an alternative imaging technique at a
      resolution beyond that of optical microscopy. By transferring cell topology into
      a rigid medium more suited for AFM imaging, many of the limitations associated
      with scanning of biological specimens can be overcome. Potential for this
      technique is demonstrated by analyzing Bioimprint replicas created from human
      endometrial cancer cells. The high resolution transfer of this process is further
      detailed by imaging membrane morphological structures consistent with exocytosis.
      The integration of soft lithography to replicate biological materials presents an
      enhanced method for the study of biological systems at the nanoscale.

PMID- 16426462
TI  - Missing value estimation for DNA microarray gene expression data by Support
      Vector Regression imputation and orthogonal coding scheme.
AB  - BACKGROUND: Gene expression profiling has become a useful biological resource in
      recent years, and it plays an important role in a broad range of areas in
      biology. The raw gene expression data, usually in the form of large matrix, may
      contain missing values. The downstream analysis methods that postulate complete
      matrix input are thus not applicable. Several methods have been developed to
      solve this problem, such as K nearest neighbor impute method, Bayesian principal
      components analysis impute method, etc. In this paper, we introduce a novel
      imputing approach based on the Support Vector Regression (SVR) method. The
      proposed approach utilizes an orthogonal coding input scheme, which makes use of
      multi-missing values in one row of a certain gene expression profile and imputes
      the missing value into a much higher dimensional space, to obtain better
      performance. RESULTS: A comparative study of our method with the previously
      developed methods has been presented for the estimation of the missing values on
      six gene expression data sets. Among the three different input-vector coding
      schemes we tried, the orthogonal input coding scheme obtains the best estimation
      results with the minimum Normalized Root Mean Squared Error (NRMSE). The results
      also demonstrate that the SVR method has powerful estimation ability on different
      kinds of data sets with relatively small NRMSE. CONCLUSION: The SVR impute method
      shows better performance than, or at least comparable with, the previously
      developed methods in present research. The outstanding estimation ability of this
      impute method is partly due to the use of the most missing value information by
      incorporating orthogonal input coding scheme. In addition, the solid theoretical
      foundation of SVR method also helps in estimation of performance together with
      orthogonal input coding scheme. The promising estimation ability demonstrated in
      the results section suggests that the proposed approach provides a proper
      solution to the missing value estimation problem. The source code of the SVR
      method is available from http://202.38.78.189/downloads/svrimpute.html for non
      commercial use.

PMID- 16426465
TI  - Endogenous carbon monoxide production correlates weakly with severity of acute
      illness.
AB  - BACKGROUND AND OBJECTIVE: The enzyme haeme oxygenase-1 is highly inducible by
      oxidative agents. Its product carbon monoxide is thought to exert anti
      inflammatory properties. We recently showed, that critically ill patients produce
      higher amounts of carbon monoxide compared to healthy controls. In the present
      study we compare endogenous carbon monoxide production with the severity of
      illness of intensive care unit patients. METHODS: Exhaled carbon monoxide
      concentration was measured in 95 mechanically ventilated, critically ill patients
      (mean age +/- SD, 59.5 +/- 15.7) on a carbon monoxide monitor. Measurements were
      taken every hour for 24 h in each patient. Data were analysed using Mann-Whitney
      rank sum test. Correlation analysis was performed with the Spearman's rank order
      correlation. RESULTS: Carbon monoxide production correlated weakly with the
      multiple organ dysfunction score (R = 0.27; P = 0.009). Patients suffering from
      cardiac disease (median 22.5, interquartile range 16.2-27.4 microL kg(-1) h(-1)
      vs. median 18.2, interquartile range 14.2-21.8 microL kg(-1) h(-1), P = 0.008)
      and critically ill patients undergoing dialysis (median 25.0, interquartile range
      21.4-30.2 microL kg(-1) h(-1), vs. median 19.4, interquartile range 14.7-23.3
      microL kg(-1) h(-1), P = 0.004) produced significantly higher amounts of carbon
      monoxide compared to critically ill controls. CONCLUSION: The findings suggest
      that endogenous carbon monoxide production might reflect the severity of acute
      organ dysfunction.

PMID- 16426463
TI  - Do people with risky behaviours participate in biomedical cohort studies?
AB  - BACKGROUND: Analysis was undertaken on data from randomly selected participants
      of a bio-medical cohort study to assess representativeness. The research
      hypotheses was that there was no difference in participation and non
      participations in terms of health-related indicators (smoking, alcohol use, body
      mass index, physical activity, blood pressure and cholesterol readings and
      overall health status) and selected socio-demographics (age, sex, area of
      residence, education level, marital status and work status). METHODS: Randomly
      selected adults were recruited into a bio-medical representative cohort study
      based in the north western suburbs of the capital of South Australia--Adealide.
      Comparison data was obtained from cross-sectional surveys of randomly selected
      adults in the same age range and in the same region. The cohort participants were
      4060 randomly selected adults (18+ years). RESULTS: There were no major
      differences between study participants and the comparison population in terms of
      current smoking status, body mass index, physical activity, overall health status
      and proportions with current high blood pressure and cholesterol readings.
      Significantly more people who reported a medium to very high alcohol risk
      participated in the study. There were some demographic differences with study
      participants more likely to be in the middle level of household income and
      education level. CONCLUSION: People with risky behaviours participated in this
      health study in the same proportions as people without these risk factors.

PMID- 16426464
TI  - Djinn Lite: a tool for customised gene transcript modelling, annotation-data
      enrichment and exploration.
AB  - BACKGROUND: There is an ever increasing rate of data made available on genetic
      variation, transcriptomes and proteomes. Similarly, a growing variety of
      bioinformatic programs are becoming available from many diverse sources, designed
      to identify a myriad of sequence patterns considered to have potential biological
      importance within inter-genic regions, genes, transcripts, and proteins. However,
      biologists require easy to use, uncomplicated tools to integrate this
      information, visualise and print gene annotations. Integrating this information
      usually requires considerable informatics skills, and comprehensive knowledge of
      the data format to make full use of this information. Tools are needed to explore
      gene model variants by allowing users the ability to create alternative
      transcript models using novel combinations of exons not necessarily represented
      in current database deposits of mRNA/cDNA sequences. RESULTS: Djinn Lite is
      designed to be an intuitive program for storing and visually exploring of custom
      annotations relating to a eukaryotic gene sequence and its modelled gene
      products. In particular, it is helpful in developing hypothesis regarding
      alternate splicing of transcripts by allowing the construction of model
      transcripts and inspection of their resulting translations. It facilitates the
      ability to view a gene and its gene products in one synchronised graphical view,
      allowing one to drill down into sequence related data. Colour highlighting of
      selected sequences and added annotations further supports exploration,
      visualisation of sequence regions and motifs known or predicted to be
      biologically significant. CONCLUSION: Gene annotating remains an ongoing and
      challenging task that will continue as gene structures, gene transcription
      repertoires, disease loci, protein products and their interactions become more
      precisely defined. Djinn Lite offers an accessible interface to help accumulate,
      enrich, and individualize sequence annotations relating to a gene, its
      transcripts and translations. The mechanism of transcript definition and
      creation, and subsequent navigation and exploration of features, are very
      intuitive and demand only a short learning curve. Ultimately, Djinn Lite can form
      the basis for providing valuable clues to plan new experiments, providing storage
      of sequences and annotations for dedication to customised projects. The
      application is appropriate for Windows 98-ME-2000-XP-2003 operating systems.

PMID- 16426466
TI  - Isoflurane and sevoflurane during reperfusion prevent recovery from ischaemia in
      mitochondrial KATP channel blocker pretreated hearts.
AB  - BACKGROUND AND OBJECTIVE: Inhalation anaesthetics given only during post
      ischaemic reperfusion have some protective effect against reperfusion injury in
      the heart. Adenosine triphosphate-regulated mitochondrial potassium channels have
      been shown to be an important mediator of cardioprotection. Thus, we investigated
      whether 5-hydroxydecanoate, a putative mitochondrial potassium channel blocker,
      prevents the cardioprotective effect of volatile anaesthetics. METHODS: Forty
      rats were randomly allocated to four groups of equal size: control group, 5
      hydroxydecanoate group, 5-hydroxydecanoate + sevoflurane group and 5
      hydroxydecanoate + isoflurane group. Seven minutes after the start of perfusion,
      normal saline (control group) or 5-hydroxydecanoate (the other groups) was
      administered. Ten minutes after the start of perfusion, the heart was rendered
      globally ischaemic for 10 min. One minute before the end of the ischaemic period,
      2.7% sevoflurane or 1.4% isoflurane were administered in the 5-hydroxydecanoate +
      sevoflurane or 5-hydroxydecanoate + isoflurane groups respectively. The heart was
      reperfused for 10 min. RESULTS: Adenosine triphosphate content at the end of
      reperfusion in the 5-hydroxydecanoate + sevoflurane group was significantly lower
      (P < 0.05) than those in the control and the 5-hydroxydecanoate + isoflurane
      groups (19.9 +/- 8.7, 28.1 +/- 3.4 and 30.4 +/- 2.3 micromol g(-1),
      respectively). In addition, the combination of inhalation anaesthetics and 5
      hydroxydecanoate decreased the ratios of recovered hearts from ischaemia (5
      hydroxydecanoate + sevoflurane group: 40%, 5-hydroxydecanoate + isoflurane group
      50%). CONCLUSION: 5-hydroxydecanoate alone caused no significant changes in
      haemodynamics and myocardial metabolism. However, the combination of 5
      hydroxydecanoate and volatile anaesthetics impaired the recovery from ischaemia.
      Although animal data cannot be extrapolated to human beings, we suggest that more
      attention be paid to patients on sulphonylurea drugs, which inhibit potassium
      channels, when they are anaesthetized with volatile anaesthetics.

PMID- 16426467
TI  - Ropivacaine myotoxicity after single intramuscular injection in rats.
AB  - BACKGROUND AND OBJECTIVE: We conducted this study in order to evaluate the
      potential myotoxic effects of ropivacaine after single injection in rats and the
      time-course of the possible damage. METHODS: One hundred and twenty-eight male
      Wistar rats were allocated to four different groups. The first three groups
      received intramuscular injections with ropivacaine 0.75%, ropivacaine 0.5% and
      normal saline, respectively, into the right tibialis anterior muscle. The fourth
      group received needle puncture without injection. Eight rats from each group were
      sacrificed 2, 4, 7 and 30 days after injection. Samples were blindly examined
      under light microscope for evidence of myotoxicity, scored as 0 = no damage to 3
      = myonecrosis and statistically analysed. Samples obtained 7 days after injection
      were also examined under transmission electron microscope. RESULTS: Ropivacaine
      0.75% and ropivacaine 0.5% caused extensive destruction to muscles fibres,
      compared to saline or needle on days 2, 4 and 7. Statistically significant
      differences were found in muscle damage by drug injections among all groups
      except for saline vs. needle groups. Thirty days after injections all sample
      appearances had returned to normal. CONCLUSIONS: Ropivacaine after single
      intramuscular injection caused reversible muscle damage in a dose-dependent
      manner.

PMID- 16426468
TI  - Gabapentin attenuates late but not acute pain after abdominal hysterectomy.
AB  - BACKGROUND AND OBJECTIVE: Gabapentin has been suggested to decrease acute
      postoperative pain. We evaluated the effect of gabapentin on pain after abdominal
      hysterectomy. METHODS: Sixty patients scheduled for abdominal hysterectomy were
      randomized to receive orally gabapentin 400 mg 6 hourly or placebo. Treatment
      started 18 h preoperatively and continued for 5 postoperative days. Pain (visual
      analogue score) and consumption of morphine for 48 h and of oral
      paracetamol/codeine were recorded after 2, 4, 8, 24 and 48 h and on days 3-5
      postoperatively. After 1 month, patients were interviewed by phone for pain, and
      analgesic intake after hospital discharge. RESULTS: Morphine consumption (mean +/
      SD) was 35 +/- 15.7 mg in the control and 28 +/- 12.1 mg in the gabapentin group
      (P = 0.21). Median number (range) of paracetamol 500 mg/codeine 30 mg tablets
      taken during days 3-5 was 1.0 (0-6) in the control and 2.0 (0-9) in the
      gabapentin group (P = 0.35). The visual analogue scores at rest and after cough
      did not differ between the two groups (F = 0.92, df = 1, P = 0.34 and F = 0.56,
      df = 1, P = 0.46, respectively). One month after surgery, 22/27 (81%) of the
      control group and 9/25 (36%) of the gabapentin group reported pain in the
      surgical area (chi(2) = 11.15, P = 0.002), while 11/27 (41%) of controls and 7/25
      (28%) of gabapentin patients consumed analgesics for pain (chi(2) = 0.93, P =
      0.39). The intensity of pain was decreased in the gabapentin group (chi(2) =
      12.6, P = 0.003). CONCLUSIONS: Gabapentin has no effect on immediate pain after
      abdominal hysterectomy but decreases pain 1 month postoperatively.

PMID- 16426469
TI  - Benchmarking as a tool of continuous quality improvement in postoperative pain
      management.
AB  - BACKGROUND AND OBJECTIVE: Quality of acute pain management is far from being
      satisfactory. These deficits are not caused by the complexity of the medical
      problem but by difficulties in organization and hospital structures, sand
      procedures. Continuous quality improvement is a recommended tool to overcome such
      difficulties and to increase quality in the long run. This study reports the
      implementation of benchmarking-based continuous quality improvement to improve
      postoperative pain management at a university hospital. METHODS: A specialised
      pain nurse interviewed patients of three surgical departments on the first day
      after surgery, and continuously assessed process and outcome quality parameters.
      A multidisciplinary team of anaesthetists, surgeons, nurses and pharmacists
      implemented a regular procedure of data analysing and internal benchmarking.
      Results and suggested improvements were fed back to the healthcare teams.
      RESULTS: From 1998 to 2002, 6,756 patients were assessed. Average pain on
      ambulation and maximal pain were 3.7 +/- 2.4 and 5.0 +/- 2.5 (mean +/- SD) on a
      11-point numeric rating scale. Pain intensity at rest was 1.9 +/- 1.8. Over time,
      pain intensity on ambulation decreased (P = 0.022) whereas maximal pain and pain
      at rest remained unchanged. There was an increase in the number of patients who
      received non-opioid analgesia (P < 0.001). CONCLUSIONS: A continuous quality
      improvement process could be established and is now successfully used in clinical
      routine. Cornerstones of this project were frequent assessments of process and
      outcome parameters, regular benchmarking and implementation of feedback
      mechanisms. Changes in organization of medical management and multidisciplinary
      teamwork seem to be more important than medical or technical aspects.

PMID- 16426470
TI  - Dexmedetomidine and meperidine prevent postanaesthetic shivering.
AB  - BACKGROUND AND OBJECTIVE: This placebo-controlled study was performed to evaluate
      the efficacy of dexmedetomidine compared with meperidine and placebo in
      preventing postanaesthetic shivering. METHODS: We studied 120 patients (ASA I-II)
      scheduled for elective abdominal or orthopaedic surgery of about 1-3 h duration.
      Forty patients in each group randomly received 1 microg kg(-1) of
      dexmedetomidine, 0.5 mg kg(-1) of meperidine or saline 0.9% as placebo,
      intravenously (i.v.). Mean arterial pressure, heart rate, oxygen saturation and
      central body temperature were measured. Extubation, awakening and orientation
      times, shivering, pain, recovery and sedation scores were recorded. RESULTS:
      Postanaesthetic shivering was seen in 22 patients in the placebo group, four
      patients in the meperidine group and six patients in the dexmedetomidine group.
      Sedation scores were significantly higher in the dexmedetomidine group compared
      with meperidine and placebo groups. Both dexmedetomidine and meperidine caused a
      significantly prolonged extubation and awakening time compared with placebo.
      Also, dexmedetomidine caused a significantly prolonged orientation time compared
      with other two groups. CONCLUSION: Intraoperative intravenously administration of
      dexmedetomidine 1 microg kg(-1) reduces postanaesthetic shivering as does
      meperidine 0.5 mg kg(-1) in patients after major surgery.

PMID- 16426471
TI  - Checking the capnograph before anaesthesia: a survey of national practice in the
      UK.
AB  - BACKGROUND AND OBJECTIVE: Recently published guidelines for checking anaesthetic
      equipment do not contain specific advice on how to check the correct functioning
      of the capnograph before inducing anaesthesia. METHODS: We undertook a postal
      survey of UK consultant (physician) anaesthetists to establish what methods for
      checking the capnograph are currently in use. Two hundred and two questionnaires
      were sent to consultants in different hospitals and 163 returned, a response rate
      of 81%. RESULTS: 52.1% consultants of check the capnograph themselves. Of these,
      55.3% use their own expired breath to confirm a response to carbon dioxide. Other
      methods used by consultant anaesthetists to check capnograph function include the
      machine self-test (16.5%), visual checks of the capnograph and sampling tubing
      (10.3%), and sampling of patient expired carbon dioxide (7.1%). CONCLUSION: The
      most common method for testing capnograph function among consultant anaesthetists
      and their assistants in the UK is the direct measurement of exhaled breath.

PMID- 16426472
TI  - High latent drug administration error rates associated with the introduction of
      the international colour coding syringe labelling system.
AB  - BACKGROUND AND OBJECTIVES: The potential for increased drug administration errors
      during the transition to the International Colour Coding syringe labelling system
      has been highlighted. The purpose of this study was to assess the potential
      effects before their introduction into our department. METHODS: Thirty-one
      anaesthetists, 19 with no previous practical experience of the new labelling
      system (Group 1), and 12 with previous experience (Group 2), volunteered to
      induce general anaesthesia for a standardized simulated patient in a designated
      theatre. They were presented with a scenario designed to suggest the need for a
      rapid sequence induction and provided with drug syringes labelled with the
      International Colour Coding system. All drug administrations were recorded.
      Active error was defined as the injection of the wrong drug. Latent error was
      defined as the selection of a syringe in error but stopping short of
      administering the drug. RESULTS: In Group 1 a total of 107 drug injections were
      recorded of which 1 (0.9%) was an active error and 16 (15%) involved latent
      errors. Eleven anaesthetists (58%) performed at least one latent error. Group 2
      had an error rate of 3%, a 6.9 (1.3-26.7) fold reduction in the rate of error (P
      = 0.023). CONCLUSIONS: Although only one drug was given in active error, latent
      errors occurred in 15% of drug administrations. The only factor conferring
      protection against error was prior experience of the new labelling system. The
      period of transition to the International Colour Coding syringe labelling system
      represents a time of increased risk of drug administration error.

PMID- 16426473
TI  - Comparison of face masks in the bag-mask ventilation of a manikin.
AB  - BACKGROUND AND OBJECTIVE: We conducted a study investigating the effectiveness of
      four face mask designs in the bag-mask ventilation of a special manikin adapted
      to simulate a difficult airway. METHODS: Forty-eight anaesthetists volunteered to
      bag-mask ventilate the manikin for 3 min with four different face masks. The
      primary outcome of the study was to calculate mean percentage leak from the face
      masks over 3 min. Anaesthetists were also asked to rate the face masks using a
      visual analogue score. RESULTS: The single-use scented intersurgical face mask
      had the lowest mean leak (20%). This was significantly lower than the mean leak
      from the single-use, cushioned 7,000 series Air Safety Ltd. face mask (24%) and
      the reusable silicone Laerdal face mask (27%) but not significantly lower than
      the mean leak from the reusable anatomical intersurgical face mask (23%).
      CONCLUSIONS: There was a large variation in both performance and satisfaction
      between anaesthetists with each design. This highlights the importance of having
      a variety of face masks available for emergency use.

PMID- 16426474
TI  - Is there a clinical need to measure the cardiac troponin I concentration before
      major abdominal surgery in high-risk patients?

PMID- 16426475
TI  - The involvement of nitric oxide on the analgesic effect of tramadol.

PMID- 16426476
TI  - Raising the head-of-bed by 30 degrees reduces ICP and improves CPP without
      compromising cardiac output in euvolemic patients with traumatic brain injury and
      subarachnoid haemorrhage: a practice audit.

PMID- 16426477
TI  - Pharmacological profile of PMS777, a new AChE inhibitor with PAF antagonistic
      activity.
AB  - The key pathophysiological mechanisms in Alzheimer's disease involve the
      selective loss of cholinergic neurons and pro-inflammatory mediator-related
      chronic inflammatory responses in the brain, therefore interventions of these
      processes are crucial to the treatment of this disease. In the present study, the
      pharmacological profile of PMS777, a new acetylcholinesterase (AChE) inhibitor
      with platelet-activating factor (PAF) antagonistic activity, has been evaluated
      in vitro and in vivo. PMS777 (1-100 microM) dose-dependently inhibited PAF
      induced rabbit platelet aggregation by competing with [3H]PAF for its receptor on
      platelets, and protected a human neuroblastoma cell line SH-SY5Y against PAF
      induced neurotoxicity. Moreover, it markedly inhibited brain AChE activity in
      mice and showed a modest selectivity for AChE (AChE: IC50=2.48+/-0.12 microM;
      butyrylcholinesterase: IC50=4.47+/-0.15 microM). Ex vivo, PMS777 (5, 10, 20 or 40
      mg/kg i.p.) reduced brain AChE activity in a dose-dependent manner. In-vivo
      studies revealed that PMS777 (0.25, 0.5, 1, 2.5 or 5 mg/kg i.p.) could reverse
      scopolamine-induced memory retrieval deficits in mice, and displayed a typical
      bell-shaped dose-response relationship. Taken together, these results demonstrate
      that PMS777 possesses dual activities for PAF receptor antagonism and AChE
      inhibition, suggesting that this compound may be a promising lead compound for
      further investigation related to the treatment for Alzheimer's disease.

PMID- 16426478
TI  - Selective antagonism at dopamine D3 receptors attenuates cocaine-seeking
      behaviour in the rat.
AB  - Dopamine (DA) D3 receptors have been suggested to play a role in mechanisms
      underlying the ability of drug-associated cues to induce drug-seeking behaviour.
      The present study investigated whether SB-277011-A, a selective DA D3 receptor
      antagonist, modulates reinstatement of cocaine-seeking behaviour induced by
      cocaine-associated stimuli. The study also explored whether or not this
      modulation is generable to seeking behaviours associated with a nutritive
      reinforcer such as sucrose. Separate groups of rats were trained to associate
      discriminative stimuli (SD) with the availability of cocaine or sucrose pellets
      vs. non-reward under a FR1 schedule of reinforcement. Each reinforced response
      was followed by a response-cue signalling a 20-s time-out (TO). After the self
      administration training criterion was met, rats underwent extinction during which
      cocaine, sucrose pellets and SDs were withheld. Reinstatement tests, separated by
      3 d during which rates of responding under extinction conditions remained at the
      criterion, were performed by presenting SDs non-contingently together with the
      contingent presentation of response-cues signalling a 20-s TO. Within- and
      between-subjects experimental designs revealed that 10 and 30 mg/kg SB-277011-A
      attenuated reinstatement of cocaine-seeking. SB-277011-A (10 mg/kg) did not
      modify conditioned reinstatement triggered by sucrose pellet-associated cues.
      These results, provided they can be extrapolated to abstinent human addicts,
      suggest the potential therapeutic use of selective DA D3 receptor antagonists for
      the prevention of cue-controlled cocaine-seeking and relapse.

PMID- 16426480
TI  - Seroprevalence of toxocariasis in Lebanon: a pilot study.
AB  - Toxocariasis is a common helminthic infection that has a worldwide distribution.
      However, data from Lebanon about the prevalence of this infection are non
      existent. We conducted a Toxocara seroprevalence study with 150 subjects
      attending the outpatient clinics at the American University of Beirut Medical
      Center between May and June 2004. Serum specimens were tested for anti-Toxocara
      antibodies by enzyme-linked immunosorbent assay and confirmed by Western blot.
      Multivariate analysis was performed to identify risk factors for infection. The
      seroprevalence rate of toxocariasis was 19%. Male gender and below high school
      education were significantly associated with a positive serological test (odds
      ratios = 3.1 and 2.8, respectively). Higher numbers of persons in the household,
      and low family income during childhood, were significant on bivariate analysis
      only. Toxocariasis is common in Lebanon. A large population-based survey is
      needed to confirm these results.

PMID- 16426479
TI  - Phenytoin, an anti-bipolar anticonvulsant: a potential anti-glucocorticoid
      mechanism?

PMID- 16426481
TI  - A loss of fecundity in a population of mudsnails Hydrobia ventrosa caused by
      larval trematodes does not measurably affect host population equilibrium level.
AB  - Host snail demography and trematode parasitism were followed for one host
      generation in a shallow brackish lagoon of the western Baltic Sea. In addition, a
      laboratory experiment was simultaneously conducted to quantify the effects of
      parasitic infection on host fecundity. Hydrobia ventrosa of the cohort of 1996
      had a maximum life-span of up to 2 years and reproduced between May and November
      of their second calendar year in 1997. Snails died after reproduction. The first
      trematode infections appeared in May 1997 when the snails started to mature.
      Total trematode prevalence peaked in summer and declined during winter to the
      lowest level in early spring 1998. Eight taxa of larval trematodes were found.
      Egg production of females with trematode infections was significantly reduced.
      Among females with pre-patent infections, about 20% were still able to produce
      eggs. Among females with patent infections merely 9% could lay eggs, compared to
      an average of about 51% in uninfected females. Taking into account a summer
      prevalence of about 25%, parasitic infections caused an overall reduction in egg
      production of the snail host population of about 15%. The reduction in host
      fecundity as a result of larval trematode infection did not measurably affect the
      population dynamics of H. ventrosa, because other environmental factors,
      especially winter severity and available food supply, were concluded to be much
      more relevant.

PMID- 16426482
TI  - Influence of Toxocara canis infection during pregnancy on offspring resistance
      towards re-infection.
AB  - The impact of Toxocara canis infection of Balb/c mice mothers on the future
      immune response of their offspring towards reinfection with the same parasite was
      studied. Two groups of offspring, the first originating from the mothers infected
      with a single dose of 1000 Toxocara canis eggs and the second from non-infected
      mothers, were both challenged with 500 T. canis eggs per animal at 6 weeks of
      age. The proportions of spleen CD4+ and CD8+ T lymphocytes, the level of serum
      cytokines IFN-gamma and IL-5, eosinophilia in peripheral blood, the production of
      specific antibodies and the number of migrating larvae were monitored. In both
      groups of offspring, the challenge infection resulted in an increase in CD4+ T
      cell subtype in comparison with the non-infected healthy control, although after
      an initial decline a subsequent increase in CD8+ was observed. The
      immunoregulation index (CD4+/CD8+) was lower in the group of mice originating
      from infected mothers throughout the whole experiment compared to the offspring
      of non-infected mothers as well as in healthy control mice of the same age. In
      the offspring of infected mothers mainly, a reduced production of IFN-gamma and
      of IL-5, suppressed eosinophilia and a higher level of protective antibodies was
      detected, compared to the control second group, in which the INF-gamma
      concentration significantly increased after day 42 p.i. In the first group of
      offspring before challenge, 12.7 +/- 2.5 larvae in the brains and 32 +/- 2.1
      larvae in the muscles transmitted from the infected mothers were detected. There
      was a significant reduction in larval recovery from brain on days 42 and 49 p.i.
      (56.7 and 56.8%, respectively), while from muscles in the same time there was a
      reduction of 46.7 and 39%, respectively, compared to the offspring of non
      infected mothers. These results indicate a significant protective memory of
      immune mechanisms against T. canis induced in offspring of Toxocara-infected
      mother mice.

PMID- 16426483
TI  - Construction of gender-enriched cDNA archives for adult Oesophagostomum dentatum
      by suppressive-subtractive hybridization and a microarray analysis of expressed
      sequence tags.
AB  - In the present study, we constructed gender-enriched cDNA libraries for the adult
      stage of the parasitic nematode Oesophagostomum dentatum (order Strongylida)
      using suppressive-subtractive hybridization (SSH), sequenced clones from the
      female-library and male-library (480 from each) and conducted bioinformatic and
      microarray analyses of the expressed sequence tags (ESTs). In total, 873 ESTs
      (440 male and 433 female) were obtained, achieving a sequencing success of 91%The
      nucleotide sequences reported in this article (Tables 1-5) have been deposited in
      the EMBL, GenBank and DDJB databases under the Accession nos. AM157797-AM158083.
      Microarray analyses of 516 unique ESTs representing both gender-enriched
      libraries revealed differential hybridization for 391 of them (75.8%). Of these,
      220 (56.3%) had significantly greater signal intensities in the female than in
      the male, and 154 (70%) of these were predicted to have homologues in C. elegans.
      These homologues were predicted to be involved in key biological processes,
      including embryonic nutrition, gametogenesis, molecular binding/transport or
      metabolism, nucleic acid synthesis and function, and signal transduction. Of the
      171 ESTs with statistically higher signal intensities in male O. dentatum, 43.8%
      had homologues in C. elegans. These homologues included major sperm proteins
      (MSPs) or MSP-like molecules, keratin-like molecules, molecules involved in
      metabolism, PDZ domain-containing proteins, sugar binding proteins, protein
      kinases, serine proteases or protease inhibitors, molecules involved in
      proteolysis and other proteins, such as enzymes and various putative proteins. Of
      the 287 ESTs (from both gender-enriched cDNA libraries) with no known homologues
      in C. elegans, 50 (17.4%) had homologues in other nematodes, 8 had homologues in
      various other organisms and 104 (36.2%) had no homology to any sequence in
      current gene databases. The present study lays a foundation for the isolation and
      molecular, biochemical and functional characterization of selected genes from the
      gender-enriched cDNA archives established for O. dentatum.

PMID- 16426484
TI  - One of the most complex life-cycles among trematodes: a description of Parvatrema
      margaritense (Ching, 1982) n. comb. (Gymnophallidae) possessing parthenogenetic
      metacercariae.
AB  - This study used light and electron microscopy to provide observations and
      morphometric details of the life-cycle of the gymnophallids (Trematoda, Digenea),
      Parvatrema margaritense (Ching, 1982) n. comb., the parthenogenetic metacercariae
      ('germinal sacs') of which were previously described by Ching (1982) as Cercaria
      margaritensis. The research was instigated by the discovery, on the Barents Sea
      coast, of a high prevalence of gymnophallid sporocysts and cercariae in the
      bivalve Turtonia minuta and an equivalent presence of distinctive gymnophallid
      metacercariae in the gastropod Margarites helicinus. Experiments and data
      obtained from naturally infected M. helicinus demonstrated that cercariae
      released from the bivalves invaded the gastropods to give rise to the
      metacercariae. Two generations (M1 and M2) of these parthenogenetic metacercariae
      were formed in the extrapallial cavities of their bivalve hosts and they, in
      turn, gave rise to a third generation (M3) which was shown to infect marine ducks
      such as the eider (Somateria mollissima). As only small numbers of cercariae are
      released from T. minuta, it was concluded that the inclusion of parthenogenetic
      metacercariae in the life-cycle is particularly significant. It allows each
      cercaria that infects M. helicinus to give rise to over 2000 invasive
      metacercariae. Evidence suggests that the parthenogenetic metacercariae are
      commensal rather that parasitic in the pallial cavities of their hosts.
      Implications of this for theories of early digenean evolution are discussed.

PMID- 16426485
TI  - Complex dynamics and stability of resistance to antimalarial drugs.
AB  - A succession of antimalarial drugs has been deployed to treat human falciparum
      malaria but each has, in turn, been nullified by the spread of drug resistance.
      The consensus view has always been that, once present, resistance will inevitably
      rapidly increase to 100%. However, recent field evidence has shown this is not
      inevitable, and that drug resistance may initially spread and then stabilize at
      relatively low frequencies. It is proposed that intense competition between
      separate malaria clones co-infecting the same human can generate complex dynamics
      capable of explaining this observation. Standard population genetic analysis
      confirms this assertion. The dynamics underlying the evolution of antimalarial
      resistance may therefore be much more complex than previously realized, and can
      resolve the apparent paradox between field data and the underlying theory of the
      evolution of resistance. This explanation is novel and the results are equally
      applicable to other parasitic species where multiple infections of the same host
      are common.

PMID- 16426486
TI  - Mild cognitive impairment: applicability of research criteria in a memory clinic
      and characterization of cognitive profile.
AB  - BACKGROUND: We explored the applicability of recently proposed research criteria
      for mild cognitive impairment (MCI) in a memory clinic and changes in case
      definition related to which memory tests are used and the status of general
      cognitive function in MCI. METHOD: A total of 166 consecutive GP referrals to the
      Cambridge Memory Clinic underwent comprehensive neuropsychological and
      psychiatric evaluation. RESULTS: Of 166 cases, 42 were excluded (significant
      depression 8, established dementia 29 and other disorders 5). Of 124 non
      demented, non-depressed patients, 72 fulfilled Petersen's criteria for amnestic
      MCI based upon verbal memory performance [the Rey Auditory Verbal Learning Test
      (RAVLT)] and 90 met criteria if performance on verbal and/or non-verbal memory
      tests [the Rey figure recall or the Paired Associates Learning test (PAL)] was
      considered. Of the 90 broadly defined MCI cases, only 25 had pure amnesia: other
      subtle semantic and/or attention deficits were typically present. A further 12
      were classed as non-amnestic MCI and 22 as 'worried well'. CONCLUSIONS:
      Definition of MCI varies considerably dependent upon the tests used for case
      definition. The majority have other cognitive deficits despite normal performance
      on the Mini-mental State Examination (MMSE) and intact activities of daily living
      (ADL) and fit within multi-domain MCI. Pure amnesic MCI is rare.

PMID- 16426487
TI  - Selective attention for negative information and depression in schizophrenia.
AB  - OBJECTIVES: Depression is a frequent feature of schizophrenia but the cognitive
      processes involved in its development and maintenance are unclear. Recent studies
      have shown that clinical depression is associated with faulty inhibitory
      mechanisms of selective attention for negative information. The current study
      examined whether patients with schizophrenia also have an attentional bias
      towards negative stimuli. The inhibitory processes of interference control and
      task-shifting abilities were also examined to assess whether patients would show
      a selective impairment. METHOD: Forty-three patients with schizophrenia and 24
      healthy controls completed the Affective Shifting Task. RESULTS: As a group,
      schizophrenia patients did not show an attentional bias for negative material.
      However, those patients with high levels of depression demonstrated faster
      latencies when negative words were the targets, and higher depression scores were
      found to be associated with an increasing number of false alarms for negative
      words when they were not the targets. The results also showed that patients had
      impaired interference control but intact task-shifting abilities. CONCLUSIONS:
      Faulty inhibitory mechanisms of selective attention for negative information are
      not a general feature of schizophrenia but appear to be selective to those with a
      depressed mood. The results highlight the need for further studies examining the
      exact nature of the affective dysfunction in schizophrenia and the cognitive
      processes supporting negative emotions.

PMID- 16426488
TI  - Reasons why some UK medical graduates who initially choose psychiatry do not
      pursue it as a long-term career.
AB  - BACKGROUND: Some doctors who initially choose psychiatry do not pursue it as a
      long-term career. The study seeks to identify reasons for leaving psychiatry.
      METHOD: Postal questionnaire survey of UK medical graduates of 1988, 1993, 1996
      and 1999 identified as having left psychiatry; for comparison, doctors who left
      general practice or trauma and orthopaedics. RESULTS: Response rate was 74%
      (572/778); 488 respondents satisfied study criteria (59 psychiatry, 318 general
      practice, 111 trauma and orthopaedics). The speciality's poor public image,
      perceived lack of respect from medical peers, perceived threat of violence from
      patients, under-resourcing and low morale were problems for psychiatry leavers.
      Job stress, self-assessed unsuitability, and concerns about the lack of evidence
      based treatments also influenced decisions to leave psychiatry. CONCLUSIONS:
      Early exposure to psychiatry may help trainees assess their suitability. Negative
      perceptions of workforce issues (e.g. low morale) and of clinical issues (e.g.
      perceived lack of ability to improve prognosis) need addressing to increase
      retention.

PMID- 16426489
TI  - Genetics of T cell defects in lupus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti
      nuclear autoantibodies that cause damage to multiple organs and tissues.
      Intrinsic defects have been demonstrated in the lymphoid and myeloid cellular
      compartments, including T cells. Lupus susceptibility is mediated through the
      interplay of a large number of genes, most of which are still unidentified. Most
      of the genetic studies in both human patients and mouse models have addressed
      lupus susceptibility as a whole. More recently however, more attention has been
      paid to the inheritance of specific lupus-associated phenotypes. In this review,
      we summarized our results obtained with the Sle1 locus in the NZM2410 mouse
      model, which mediates the generation of anti-histone autoreactive T cells. Sle1,
      which is constituted of multiple genes, is the only known genomic region that is
      sufficient for the generation of autoreactive T cells. The identification of the
      corresponding genes will constitute a landmark for our understanding of the
      mechanisms of autoimmunity. Our results are discussed in the context of candidate
      genes and the role of T cells in systemic autoimmunity.

PMID- 16426491
TI  - Activation of c-Jun N-terminal kinases by ribotoxic stresses.
AB  - The c-Jun N-terminal kinases (JNKs) are classic stress-activated protein kinases.
      Many cellular stresses have been shown to stimulate JNK activation. In this
      review, we focus on ribotoxic stresses based on their multiple biological
      potencies including anti-HIV-1 activity. Some of the functions of ribotoxins and
      the signaling transduction pathway that mediated are mentioned. Different from
      other stimulators, ribotoxic stresses act on special motifs of 28S rRNA in
      translationally active mammal ribosomes. Binding and damaging on the motif leads
      to JNK activation and subsequently biological response to the signal initiator,
      which is named ribotoxic stress response.

PMID- 16426492
TI  - BTLA, a new inhibitory B7 family receptor with a TNFR family ligand.
AB  - B and T lymphocyte attenuator (BTLA), identified as an immune inhibitory receptor
      recently, plays widespread roles on T and B cells. Emerging evidence has
      generated plentiful information on the mechanisms which BTLA mediates negative
      regulation in immune responses and involves in a variety of physiological and
      pathological processes. The exploration of the biological mechanisms and
      regulation of BTLA will open possibilities on novel therapeutic strategies in
      immune-related diseases.

PMID- 16426490
TI  - Plasmacytoid dendritic cells act as the most competent cell type in linking
      antiviral innate and adaptive immune responses.
AB  - Appropriate in vivo control of plasmacytoid dendritic cell (pDC) recruitment and
      activation is a fundamental requirement for defense against viral infection.
      During this process, a pivotal event that influences the outcome of viral
      infection is the production of high levels of type I interferon by pDCs. In
      particular, recent research findings showed that pDCs not only shape the nature
      of innate resistance, but are also responsible for the successful transition from
      innate to adaptive immunity for viral resistance. In addition, pDCs can
      differentiate into antigen presenting cells that may regulate tolerance to a
      given pathogen. Importantly, in a series of recent clinical studies, pDCs
      appeared to be defective in number and function in conditions of chronic viral
      diseases such as infected with HIV-1, HBV or HCV. pDC-associated clinical
      antiviral therapy is also emerging. This review describes research findings
      examining the functional and antiviral properties of in vivo pDC plasticity.

PMID- 16426493
TI  - Immunological aspects of the statins' function in patients with heart failure: a
      report from the Annual Conference of ESC - Heart Failure 2005.
AB  - The annual meeting of the Heart Failure Association of ESC in Lisbon, in June
      2005, was exceptionally successful. There were many very interesting
      presentations and workshops with the unique title: Statins in heart failure-
      Cholesterol-lowering is not the only goal. Heart failure (HF) is a progressive
      disease with coronary artery disease (CAD) as the most often underlying etiology.
      Treatment to prevent progression of heart failure has been targeted to reverse
      the consequences of HF and to a less extent the cause - the atherosclerotic
      plaque itself. On the average 50% of patients with heart failure are treated with
      lipid intervention. Lipid-lowering treatment with statins clearly reduces
      morbidity and mortality of patients with documented CAD. Since the prevalent
      etiology of heart failure is CAD, its prevention may reduce heart failure
      progression. However, recent studies suggest that pleiotropic effects of statins
      are more important than the influence related to their cholesterol lowering
      mechanism. Furthermore it is suggested that low levels of circulating
      lipoproteins and cholesterol may be independent predictors of impaired outcome in
      patients with heart failure. There are some possible explanations for this
      finding. High levels of cholesterol can be beneficial to heart failure patients;
      cholesterol-rich serum lipoproteins are able to modulate inflammatory immune
      function because they bind and detoxify bacterial lipopolysaccharide, a very
      strong stimulator of the release of proinflammatory cytokines that promote heart
      failure progression and death. So current recommendations strongly emphasize that
      the aim of treatment of HF is not to lower cholesterol.

PMID- 16426495
TI  - TLR3 ligand-induced accumulation of activated splenic natural killer cells into
      liver.
AB  - It has been revealed that poly I:C is a potent stimulator for NK cells, which can
      induce NK cell rapid activation and preferential accumulation into liver.
      However, the process mediating the influx of NK cells remains obscure. In this
      study, we found that poly I:C administration increased the portion and absolute
      number of NK cells in liver, but largely decreased those in spleen. There were no
      obvious changes of these lymphocytes in other immune organs. The results from
      splenic adoptive transfer and splenectomy showed that the recruited spleen NK
      cells contributed to the accumulation of NK cells in liver, and this process was
      regulated by the production of chemokines and the presence of T cells. This
      investigation will help to understand the enhanced immune cell recruitment in
      liver upon viral infection.

PMID- 16426494
TI  - FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental
      autoimmune encephalomyelitis by inhibition of T cell infiltration.
AB  - FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease
      in the number of peripheral blood lymphocytes and exerts immunomodulating
      activity in various experimental allograft and autoimmune disease models. In this
      study, we evaluated the effect of FTY720 and its active metabolite, (S)
      enantiomer of FTY720-phosphate [(S)-FTY720-P] on experimental autoimmune
      encephalomyelitis (EAE) in rats and mice. Prophylactic administration of FTY720
      at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and
      therapeutic treatment with FTY720 significantly inhibited the progression of EAE
      and EAE-associated histological change in the spinal cords of LEW rats induced by
      immunization with myelin basic protein. Consistent with rat EAE, the development
      of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented
      and infiltration of CD4(+) T cells into spinal cord was decreased by prophylactic
      treatment with FTY720 and (S)-FTY720-P. When FTY720 or (S)-FTY720-P was given
      after establishment of EAE in SJL/J mice, the relapse of EAE was markedly
      inhibited as compared with interferon-beta, and the area of demyelination and the
      infiltration of CD4(+) T cells were decreased in spinal cords of EAE mice.
      Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte
      glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720
      exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and
      mice, and that the effect of FTY720 on EAE appears to be due to a reduction of
      the infiltration of myelin antigen-specific CD4(+) T cells into the inflammation
      site.

PMID- 16426496
TI  - The inhibitory effect of quercetin on IL-6 production by LPS-stimulated
      neutrophils.
AB  - Quercetin is a herbal flavonoid derived from various foods of plant origin and
      plays a role in anti-inflammation. Although a number of researches in the field
      have been done, the mechanism of anti-inflammatory effect of quercetin should be
      further clarified. In the present study, we investigated the effects of quercetin
      on IL-6 production by LPS-stimulated neutrophils in human. Neutrophils were were
      pre-treated with quercetin at the final concentrations of ranging from 0-80
      microM for 30 min, or not treated, and then incubated in the presence or absence
      of lipopolysaccharide (LPS) at a final concentration of 100 ng/ml for indicated
      time. The secretion level of IL-6 in the culture supernatants was assayed by
      ELISA, the intracellular level of IL-6 was detected by flow cytometry and the
      expression of IL-6 mRNA was analyzed by RT-PCR. The experiment results showed
      that neutrophils cultured with medium or quercetin alone did not express IL-6,
      but LPS (100 ng/ml) induced IL-6 expression of neutrophils. However, after pre
      treatment of neutrophils with quercetin (40 microM) for 30 min, the inducible
      effects of LPS on the increase of IL-6 secretion, intracellular IL-6 level and IL
      6 mRNA expression by neutrophils were abrogated. IL-6 is one of the important pro
      inflammatory factors, especially in early phage of inflammation. Thus, our data
      suggested that quercetin might exert its anti-inflammatory effect through
      negatively modulating pro-inflammatory factors, such as IL-6. The inhibitory
      effects of quercetin on IL-6 production by neutrophils may provide a theoretical
      basis on future therapy of inflammation.

PMID- 16426497
TI  - The effect of CD3-specific monoclonal antibody on treating experimental
      autoimmune myasthenia gravis.
AB  - CD3-specific monoclonal antibody was the first one used for clinical practice in
      field of transplantation. Recently, renewed interests have elicited in its
      capacity to prevent autoimmune diabetes by inducing immune tolerance. In this
      study, we tested whether this antibody can also be used to treat another kind of
      autoimmune disease myasthenia gravis (MG) and explored the possible mechanisms.
      MG is caused by an autoimmune damage mediated by antibody- and complement
      mediated destruction of AChR at the neuromuscular junction. We found that
      administration of CD3-specific antibody (Fab)2 to an animal model with
      experimental autoimmune myasthenia gravis (EAMG) (B6 mice received 3 times of
      AChR/CFA immunization) could not significantly improve the clinical signs and
      clinical score. When the possible mechanisms were tested, we found that CD3
      antibody treatment slightly down-regulated the T-cell response to AChR, modestly
      up-regulating the muscle strength. And no significant difference in the titers of
      IgG2b was found between CD3 antibody treated and control groups. These data
      indicated that CD3-specific antibody was not suitable for treating MG, an
      antibody- and complement- mediated autoimmune disease, after this disease has
      been established. The role of CD3-specific antibody in treating this kind of
      disease remains to be determined.

PMID- 16426498
TI  - The effect of anti-human CD134 monoclonal antibody on phytohemagglutinin-induced
      mRNA expression of perforin in peripheral blood mononuclear cells.
AB  - CD134, a member of the tumor necrosis factor receptor superfamily, plays a
      crucial role in T cell survival. In this study, peripheral blood mononuclear
      cells (PBMCs) stimulated with phytohemagglutinin (PHA, 50 microg/ml) were treated
      by CD134 mAb (1 microg/ml, 5 microg/ml, 10 microg/ml) for 6 h, 12 h, 24 h and 48
      h. The level of perforin mRNA was measured by reverse transcription-polymerase
      chain reaction (RT-PCR) technique. Our data showed that the expression of
      perforin mRNA in PBMCs was down-regulated by CD134 mAb in a dose-dependent manner
      in range of 1 microg/ml to 5 microg/ml and dropped down to its minimum on 24 h
      (p<0.05). The level of perforin mRNA reached a plateau when the concentration of
      CD134 mAb exceeded 5 microg/ml. In conclusion, CD134 mAb can inhibit perforin
      expression, which may enhance the ability of T cells for survival.

PMID- 16426500
TI  - As per manufacturer's instructions.

PMID- 16426499
TI  - Bifidobacteria DNA induces murine macrophages activation in vitro.
AB  - Previous studies have shown that oligodeoxynucleotides containing unmethylated
      CpG motifs were used as adjuvants for immunoregulation and immune response. This
      study was to explore the activation effects of Bifidobacteria DNA containing
      unmethylated CpG motifs (CpG DNA) on murine macrophage J774A.1 cells. The genomic
      DNA of Bifidobacteria was extracted and purified, and the methylation degree of
      CpG motifs was tested. The phagocytic ability of the macrophages was detected by
      flow cytometry. The cytokines (IL-1beta, IL-6, IL-12p40 and TNF-alpha) levels in
      the culture supernatants of Bifidobacteria DNA treated J774A.1 cells were assayed
      by ELISA. The content of nitric oxide (NO) was detected by Griess reagent. After
      treated with Bifidobacteria DNA for 24 h, Nile Red stain increased in J774A.1
      macrophage, which suggested that the lipid metabolism increased in the
      macrophages. The phagocytic ability and levels of NO and cytokines of IL-1beta,
      IL-6, IL-12p40 and TNF-alpha were significantly higher than PBS group and CT DNA
      group. The results indicated that Bifidobacteria DNA could activate murine
      macrophages J774A.1, which could provide scientific basis for the research and
      application of microorganism DNA preparation.

PMID- 16426501
TI  - Caries detection.

PMID- 16426502
TI  - Predictable periimplant gingival esthetics: use of the natural tooth as a
      provisional following implant placement.
AB  - Maintaining the interdental papilla and bone height following implant placement
      has been a challenge for the restorative dentist. Bone resorption following
      anterior tooth extraction is common and often compromises the esthetics of the
      final restoration. The tissue must be maintained during the surgical and healing
      phases to achieve an esthetic outcome. Using the patient's natural tooth as a
      provisional can help maintain the volume and support the papilla. This article
      describes a technique to achieve maximum esthetics and preservation of tissue
      following tooth extraction and implant placement. CLINICAL SIGNIFICANCE: By using
      the patient's extracted natural tooth, the tissue should maintain itself with
      minimal recession. This will allow for a more esthetic outcome.

PMID- 16426505
TI  - Shear bond strength with increasing light-guide distance from dentin.
AB  - BACKGROUND: In Class II composite restorations, the adhesive covering the
      gingival floor of the deep cavity preparation is 2 to 8 mm from the light guide
      and may not be adequately cured with a typical 10-second curing time. PURPOSE:
      The purpose of this study was to evaluate the dentin bond strengths of resin
      composite when the curing light guide (quartz-tungsten-halogen light) was placed
      at various distances and to investigate the relationships between radiant
      exposure, degree of conversion, and shear bond strength. MATERIALS AND METHODS:
      Single Bond (3M ESPE, St. Paul, MN, USA) was placed onto the dentin following the
      manufacturer's directions. Four groups of 10 teeth were cured for 20 seconds
      through a 0, 2.3, 4.6, or 6.9 mm spacer. Two other groups of 10 teeth were cured
      through a 4.6 mm spacer for 40 seconds and 60 seconds, respectively. Z100 resin
      composite (3M ESPE) was placed over the cured adhesive and polymerized at the
      same distance as the adhesive. After 24 hours of storage in water, the shear bond
      strengths were tested. The irradiance through each spacer was measured using a
      digital radiometer. The degree of conversion of the adhesive was determined by
      near infrared spectroscopy. The data were analyzed using analysis of variance and
      Tukey-B post hoc tests. RESULTS: Dentin shear bond strengths decreased
      significantly with increasing distance, but they increased significantly when the
      curing time increased from 20 to 40 or 60 seconds. There is a linear correlation
      between shear bond strength, degree of conversion, and logarithm (radiant
      exposure). CONCLUSION: Increasing curing time can compensate for the decreased
      bond strength owing to a decreased irradiance associated with increased curing
      distance. CLINICAL SIGNIFICANCE: Under the conditions of this study, when curing
      the adhesives in deep proximal boxes with a quartz-tungsten-halogen light, the
      curing time should be increased to 40 to 60 seconds to ensure optimal
      polymerization.

PMID- 16426507
TI  - Effect of resin liners and photoactivation methods on the shrinkage stress of a
      resin composite.
AB  - PURPOSE: This study was undertaken to evaluate the effect of three different
      photoactivation methods on the polymerization shrinkage stress of a resin
      composite using different resin liners. MATERIALS AND METHODS: Three
      photoactivation methods using a quartz-tungsten-halogen light were evaluated:
      continuous light, soft start, and intermittent light. Three lining groups were
      tested: one or three coats of adhesive, and flowable composite. The stress was
      measured using a universal testing machine. After the stress measurement, Knoop
      hardness numbers (KHNs) were evaluated to verify indirectly the degree of
      conversion of the composite using the three photoactivation methods. The data
      were submitted to analysis of variance and Tukey's test (p < .05). RESULTS:
      Intermittent light was always associated with statistically lower stress values
      when compared with continuous light. Statistical differences were not observed
      when continuous light and soft start were compared. The use of a flowable
      composite liner significantly reduced the stress generation when compared with
      the use of one adhesive coat. The three adhesive coats groups showed intermediate
      stress values. The hardness test showed no statistical difference between that
      achieved with continuous light and soft start. These two methods showed
      statistically higher KHNs when compared with results with intermittent light.
      CLINICAL SIGNIFICANCE: Photoactivation using intermittent light may lead to a
      significant reduction in shrinkage stress levels. This effect could be attributed
      to a significant reduction of the polymerization rate and/or a decrease in the
      degree of conversion. The use of a flowable composite liner reduced the stress
      levels when compared with levels when one coat of adhesive was used. This is
      possibly related to the higher thickness of the flowable composite layer.

PMID- 16426503
TI  - Esthetic management of fused carious teeth: a case report.
AB  - A rare case of a carious supernumerary tooth fused to the labial surface of a
      maxillary right central incisor is reported. Root canal therapy on the maxillary
      right central incisor was performed owing to the pulpal communication between the
      supernumerary tooth and the maxillary right central incisor after removing the
      carious supernumerary tooth structure. The defect was then restored with anterior
      resin composite and the esthetics reestablished. CLINICAL SIGNIFICANCE: Clinical
      significance lies in identifying a rare case of fusion of supernumerary tooth to
      a permanent tooth and treating the anomaly in the most conservative way.

PMID- 16426509
TI  - Influence of temperature on the spreading velocity of simplified-step adhesive
      systems.
AB  - BACKGROUND: Flowability and viscosity vary for different adhesive systems owing
      to differences in their composition. These characteristics can be modified by
      environmental temperature. PURPOSE: The purpose of this study was to determine
      the influence of temperature on the spreading (flow capacity) of simplified-step
      adhesive systems. MATERIALS AND METHODS: Spreading velocities of adhesive systems
      (Adper Single Bond and Single Bond Plus [3M ESPE, St. Paul, MN, USA]; Prime &
      Bond 2.1 and Prime & Bond NT [Dentsply Industria e Comercio Ltda, Petropolis, RJ,
      Brazil]; Adper Prompt [3M ESPE]; and One Up Bond F [Tokuyama Corp, Tokyo, Japan])
      were analyzed at intervals of 10, 15, 20, and 30 seconds at both 25 degrees C and
      37 degrees C by placing 10 microL drops on a glass slide surface with an
      inclination of 45 degrees. The spreading of each adhesive system was measured in
      millimeters per second. RESULTS: Data were analyzed by two-way analysis of
      variance and Student-Newman-Keuls tests. Regression analysis was used to
      determine a correlation between spreading velocity and time. Statistical
      significance was considered at a confidence level of 95%. Temperature influenced
      the spreading velocity, increasing it for Single Bond and Prime & Bond 2.1 and
      decreasing it for Adper Prompt (p < .05). No differences on spreading were
      observed for the other adhesives studied (p >.05). Regression analysis of each
      adhesive system demonstrated an inverse correlation between mean spreading
      velocity and time (R2 = .999) on both temperatures. CONCLUSIONS: Temperature
      increases yielded an increase of spreading for Single Bond and Prime & Bond 2.1.
      The influence of temperature on the spreading velocity was material dependent.
      CLINICAL SIGNIFICANCE: Environmental temperature can influence the rate of
      spreading of the adhesive system in clinically relevant times and may influence
      adhesive thickness on cavity walls.

PMID- 16426511
TI  - Effects of porcelain leucite content, types of etchants, and etching time on
      porcelain-composite bond.

PMID- 16426514
TI  - Lasers in dentistry.

PMID- 16426515
TI  - [New treatments for idiopathic pulmonary fibrosis].

PMID- 16426513
TI  - Critical appraisal. Porcelain veneer outcomes, part I.
AB  - Etched porcelain veneers have now been used clinically for about 20 years. The
      profession was originally very skeptical about bonding thin shells of a brittle
      ceramic material to teeth. However, ceramic veneers have proved to be not only
      very esthetic but also extremely durable restorations. This two-part Clinical
      Appraisal reviews several articles related to veneer longevity and clinical
      factors contributing to--or detracting from--longevity. Part II will appear in
      the next issue of JERD.

PMID- 16426516
TI  - [Attitudes toward the diagnosis of chronic obstructive pulmonary disease in
      primary care].
AB  - OBJECTIVE: Although the prevalence of chronic obstructive pulmonary disease
      (COPD) has increased among women, it is still considered a disease that mainly
      affects men. This study aimed to identify the diagnostic attitudes of primary
      care physicians toward patients with COPD according to gender and spirometric
      results. METHODS: A representative sample of 839 primary care physicians
      participated in the study. Each physician dealt with 1 of 8 hypothetical cases
      based on a patient diagnosed with COPD. In half the cases, the physician was told
      the patient was a man. The other half of the physicians were told the same
      patient was a woman. After presentation of the medical history and results of
      physical examination, the physicians were asked to state a probable diagnosis and
      indicate the diagnostic tests that were necessary. They were then told the
      results of spirometry, which indicated obstruction ranging from moderate to
      severe. Negative results of bronchodilator tests and oral corticosteroid tests
      were then communicated. RESULTS: COPD was more likely to be the preliminary
      diagnosis for male patients than for females (odds ratio [OR], 1.55; 95%
      confidence interval [CI], 1.15-2.1). This gender bias disappeared once the
      physicians were shown the abnormal results of spirometry. Patients with severe
      obstruction were more likely to be diagnosed with COPD than those with moderate
      obstruction (OR, 1.5; 95% CI, 1.08-2.09). CONCLUSIONS: There is gender bias in
      the diagnosis of COPD. Patients with moderate obstruction are often believed not
      to have COPD. These biases may compromise the early diagnosis of the disease in a
      group of patients with ever increasing risk.

PMID- 16426517
TI  - [Risk factors for atrial fibrillation after thoracic surgery].
AB  - OBJECTIVE: To determine the risk factors for atrial fibrillation after lung
      resection. PATIENTS AND METHODS: Between January 2002 and December 2003, 149
      patients underwent lung resection in our hospital. For all these patients,
      clinical, surgical, analytical, and oncological data were prospectively
      collected. The data were subjected to univariate analysis. RESULTS: The mean (SD)
      age of the 127 men (85.2%) and 22 women (14.8%) who underwent lung resection was
      61.8 (12.3) years (range, 17-79 years). Atrial fibrillation was documented in 17
      patients (11.4%). Mortality at 30 days was 8.1%. The following risk factors for
      atrial fibrillation were identified: age 70 years or older (P<.0004), prior heart
      disease (P<.005), patients undergoing operations for lung cancer (P<.04), and
      type of resection--right bilobectomy (P<.05) and left pneumonectomy (P<.03).
      Hypertension, chronic obstructive pulmonary disease, and lung cancer stage were
      not risk factors. Likewise, systematic lymph node dissection and other forms of
      lung resection were not risk factors. CONCLUSIONS: After lung resection, atrial
      fibrillation is a common complication that seems to be associated with old age,
      history of heart disease, operations for lung cancer, left pneumectomy, and right
      bilobectomy. The identification of these risk factors may encourage prospective
      studies that assess the use of antiarrhythmic drugs to prevent atrial
      fibrillation during chest surgery.

PMID- 16426518
TI  - [Sleep-disordered breathing in patients with difficult-to-control hypertension].
AB  - OBJECTIVE: To analyze the relationship between sleep-disordered breathing and
      difficult-to-control arterial hyper-tension. PATIENTS AND METHODS: Patients were
      considered to have difficult-to-control hypertension when mean systolic blood
      pressure was 125 mm Hg or higher and/or mean diastolic blood pressure was more
      than or equal to 80 mm Hg (as recorded during 2 24-hour ambulatory monitoring
      studies) despite the use of 3 or more antihypertensive drugs. Respiratory
      polygraphy using the AutoSet device (ResMed Corp, Sydney, Australia) was then
      performed to study sleep-disordered breathing in all patients. RESULTS: Forty
      nine patients with a mean (SD) age of 68.1 (9.1) years, mean systolic and
      diastolic pressures of 152.5 (13)/89.2 (8.5) mm Hg, and an average of 3.5
      prescribed drugs were included in the study. The mean apnea-hypopnea index (AHI)
      was 26.2 (19.5) and events were predominantly obstructive. Patients with severe
      sleep apnea-hypopnea syndrome (SAHS) (AHI > or = 30; 40.8%) showed more
      uncontrolled daytime (P = .017) and nighttime (P = .033) systolic pressure than
      the rest, as well as higher daytime diastolic pressure (P = .035) and a greater
      consumption of drugs than those without severe SAHS (AHI < 10; 28.6%) (P = .041).
      The study population as a whole showed a significant correlation between blood
      pressure and obesity. There was a significant correlation (adjusted for age and
      sex) with AHI only in patients with SAHS. AHI was found to be the independent
      predictor with the greatest effect on blood pressure in these patients.
      CONCLUSIONS: Prevalence of SAHS was very high in patients with difficult-to
      control hypertension. In patients with SAHS, AHI was found to be the independent
      predictor with the greatest affect on arterial blood pressure.

PMID- 16426519
TI  - [Smoking among adolescents: population study on parental and school influences].
AB  - OBJECTIVE: Smoking represents a public health problem, one which begins during
      adolescence. The main objective of this study was to analyze the association
      between smoking and parental and school factors. SUBJECTS AND METHODS: The study
      sample consisted of the students from the 20 secondary schools in the region of
      Osona, Barcelona, Spain. A self-report questionnaire was used to obtain
      information on the following variables: smoking habit, age of initiation,
      frequency, type of school (state school or private-subsidized), sex, age, persons
      living in the home, town, whether the student had lunch at school, whether the
      student often had lunch or dinner alone at home. RESULTS: A total of 2280
      students participated in the study (91%). Mean age was 15.5 years. Of the
      participants, 20% said they were smokers; 5%, ex-smokers; 34% had tried smoking
      at least once, and 41% had never smoked. Factors significantly associated with
      smoking in the multivariate analysis were age, rural town, state school, single
      parent family, eating alone, and not lunching at school. CONCLUSIONS: Smoking
      prevalence is high among adolescents in our society and there is no gender
      difference. Our results show that family structure and dynamics can influence
      smoking in adolescents. Smoking is less prevalent among adolescents who have
      lunch at school.

PMID- 16426520
TI  - [Origin and development of RUTI, a new therapeutic vaccine against Mycobacterium
      tuberculosis infection].
AB  - This article reviews the pathophysiology of the latent form of Mycobacterium
      tuberculosis along with its natural history and progression in infected tissues.
      The proposed hypotheses regarding the relationship between M tuberculosis and the
      associated immune response, the cause of granuloma necrosis, the tolerance of a
      certain concentration of the bacillus in host tissues, the constant turnover of
      cells in the lung, and the effect of chemotherapy form the basis for the design
      of the therapeutic vaccine RUTI against latent M tuberculosis infection. This
      vaccine is generated from detoxified M tuberculosis cell fragments that
      facilitate a balanced T helper (Th) 1/Th2/Th3 response to a wide range of
      antigens along with intense antibody production. Treatment with RUTI following
      chemotherapy has been demonstrated to be effective in experimental models in mice
      and guinea pigs and does not exhibit toxicity.

PMID- 16426521
TI  - [Nasal potential difference test to diagnose cystic fibrosis].
AB  - Cystic fibrosis is usually diagnosed based on suspicion arising from a typical
      clinical picture and must be confirmed by either a finding of high chloride
      concentrations in sweat tests on 2 separate days or detection of 2 gene
      mutations. The nasal potential difference (NPD) test has been proposed to provide
      evidence of abnormal function of the cystic fibrosis transmembrane conductance
      regulator (CFTR), a receptor that forms a chloride ion channel. The test is
      especially useful for patients who have normal chloride concentrations in sweat
      tests and in whom 2 gene mutations related to cystic fibrosis have not been
      detected. The NPD test requires 2 electrodes connected to a voltmeter (a Tholy
      Medicap device). One is placed on the nasal mucosa of the inferior turbinate and
      the other is placed subcutaneously on the forearm. A reading less than -40 mV is
      considered abnormal, as values under that cut point are never found in healthy
      individuals. Two abnormal NPD findings on separate days are required for a
      diagnosis of CFTR dysfunction. False negatives arise when the integrity of the
      epithelium is altered. After application of amiloride, NPD decreases more
      markedly in cystic fibrosis patients than in healthy individuals and applying
      isoproterenol or fenoterol after amiloride provokes no response in patients with
      the genetic defect that prevents chloride ion channel activation.

PMID- 16426522
TI  - [Pulmonary varix inside a bulla].
AB  - Pulmonary varices are uncommon vascular abnormalities that are usually
      asymptomatic and so they are normally diagnosed by chance from a chest x-ray.
      They often present as a pulmonary nodule and can be either congenital or
      acquired. If acquired, they are associated with pulmonary venous hypertension,
      usually as a result of mitral valve disease. Pulmonary arteriography provides a
      definitive diagnosis, although the use of new noninvasive imaging techniques is
      spreading. Treatment is not normally required unless serious complications arise.
      We present the case of a pulmonary varix located within a pulmonary bulla. This
      form of presentation has not been previously reported.

PMID- 16426523
TI  - [Strong suspicion of lung toxicity due to riluzole].
AB  - Riluzole is a drug used in the treatment of amyotrophic lateral sclerosis. To
      date, reports of lung toxicity have been exceptional. We present the case of a 74
      year-old man diagnosed with amyotrophic lateral sclerosis. Following 3, 5 months
      of treatment with riluzole (Rilutek), the patient began to present a clinical
      picture consisting of nonproductive cough, progressive dyspnea (even with slight
      exertion), weakness, and radiologic progression with the appearance of
      predominantly peripheral bilateral pulmonary infiltrates that did not respond to
      treatment with amoxicillin-clavulanic acid. Bacterial tests did not reveal the
      presence of germs, nor did other examinations suggest an alternative diagnosis.
      The patient did not resume treatment with the drug or undergo complementary
      procedures aimed at obtaining histologic samples. Nevertheless, the coincidence
      in time, lack of response to antibiotic treatment, remission of symptoms
      following withdrawal of the drug without initiating any other treatment except 40
      mg/d of methylprednisolone for 6 days, absence of alternative diagnoses, and
      suggestive clinical and radiologic findings all together point to toxicity due to
      riluzole.

PMID- 16426524
TI  - [Do parents of asthmatic children feel their own asthma is under control?].

PMID- 16426525
TI  - [Idiopathic bronchocentric granulomatosis].

PMID- 16426526
TI  - [Gastrointestinal stromal tumors: new concepts and multidisciplinary medico
      surgical therapeutic strategies].

PMID- 16426528
TI  - [Laparoscopic surgery in Europe. Where are we going?].
AB  - The most important factors that have facilitated the development of laparoscopic
      surgery (LS) are technological innovations and the vision of a small number of
      surgeons who took advantage of these advances. There are few surgical innovations
      that have stimulated such controversies and concerns and have raised so many
      medico-legal issues as LS. Although much progress has been made in LS, some
      important controversies remain unresolved, which are reviewed in the present
      article: 1. Evolution of the laparoscopic approach: total laparoscopic approach
      through positive-pressure capnoperitoneum, gasless laparoscopy, hand-assisted
      laparoscopy, and laparoscopy-assisted surgery. 2. Classification of current
      instrumental technology in laparoscopic surgery: a) facilitating instruments
      (high-power ultrasonic dissection systems); b) enabling instruments (endostapling
      and linear dissection devices), and c) complementary instruments: the Da Vinci
      robotic system. 3. Current laparoscopic surgical practice: a) interventions that
      definitively improve the patient's outcome (diagnostic and staging laparoscopy,
      cholecystectomy, adrenalectomy, splenectomy, antireflux surgery, cardiomyotomy,
      bariatric surgery, laparoscopic colon surgery, living donor nephrectomy); b)
      interventions that seem to be useful to the patient (distal pancreatic surgery,
      laparoscopic left hepatic resection, gastric and esophageal resections,
      hernioplasty), and c) interventions with uncertain benefit (right hepatectomy,
      pancreatoduodenectomy). 4. Future lines of development: video monitors in
      laparoscopic surgery, endoluminal surgery, robotic surgery, and finally, 5.
      Problems faced by laparoscopic surgery: quality guarantees in laparoscopic
      surgery, training the future laparoscopic generation, and allocation of
      sufficient material and human resources to laparoscopic surgery and its
      subspecialties.

PMID- 16426527
TI  - [The importance of surgical margins in conservative surgery for breast cancer].
AB  - In the last few decades, conservative surgery has become an option in the
      surgical treatment of breast cancer. The success of conservative surgery depends
      not only on appropriate patient selection but also on the combination of adequate
      surgical margins and an acceptable cosmetic result. Obtaining negative surgical
      margins in conservative breast surgery influences the incidence of local disease
      recurrence and probably overall survival. Therefore, it is essential to optimize
      intraoperative examination of margins as well as to explore new techniques that
      would achieve the greatest possible percentage of negative margins.

PMID- 16426529
TI  - [Gastrointestinal stromal tumors. Diagnosis, prognosis and current surgical
      treatment. Follow-up of 18 treated patients].
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most frequent
      mesenchymal tumors of the digestive tract and their growth is directed through
      the signaling of the KIT or PDFGRA genes. The objective of the present study was
      to describe a series of cases of GIST tumors located in the stomach. PATIENTS AND
      METHODS: We performed a retrospective, descriptive study of 18 patients diagnosed
      with gastric GIST and treated by means of gastric resection between July 1996 and
      June 2004. There were 12 women and six men, with a mean age of 63 years (range 33
      84). In all patients, diagnosis was performed with immunohistochemical markers,
      such as CD34 and CD117. Investigations included endoscopy, abdominal
      ultrasonography, abdominal computerized axial tomography and fine-needle
      aspiration biopsy. RESULTS: The main symptoms were digestive hemorrhage with
      severe anemia in 10 patients and abdominal pain in seven. In two patients, the
      tumors were incidental findings during laparotomy. Four patients underwent
      emergency surgery and the remainder underwent elective surgery. In all patients,
      gastric resection of variable extension was performed, according to tumoral
      location. Multicentric tumors were found in two patients. All patients were CD117
      and CD34-positive. There were few postoperative complications. One patient died
      from acute myocardial infarction (5.6%). The mean follow-up was 47.5 months
      (range, 12-106). One patent died due to spread of a pancreatic neoplasm and the
      remaining patients are alive and without tumoral recurrence (94.1%). CONCLUSIONS:
      Initial symptoms consist of upper gastrointestinal hemorrhage and abdominal pain.
      Gastroscopy and imaging techniques lead to a suspected diagnosis, which can be
      confirmed by immunohistochemical studies, in which the "gold standard" is
      positivity for CD117; CD34 (+), vimentin (+), actin (-) and protein S-100 (-) are
      also used. Treatment consists of tumoral resection with negative margins.

PMID- 16426530
TI  - [Immediate peritoneal response to contamination during laparoscopic surgery in an
      experimental mouse model].
AB  - INTRODUCTION: Several studies have shown that laparoscopic surgery (LS) minimizes
      surgical trauma and preserves immune response. Another advantage is the lower
      incidence of infectious complications. However, several in vitro studies have
      shown that an atmosphere with CO2 affects macrophage physiology, which would
      affect the response to peritoneal contamination. This observation is
      controversial, given the experimental evidence of a better conserved response to
      peritoneal contamination. The aim of the present study was to investigate the
      immediate response of the peritoneum to contamination in an atmosphere with CO2.
      MATERIAL AND METHOD: A total of 192 CD-1 rats were distributed into three groups:
      group I, LP, n= 64, (laparotomy); group II, LC-CO2, n= 64, (laparoscopy-CO2),
      group III, LC-T, n= 64, (laparoscopy-traction). The rats were randomized to
      receive 1 ml of a suspension of Escherichia coli (1x10(4) CFU/ml) (contamination
      [C]) or saline serum (no contamination [NC]). Peritoneal fluid was obtained at
      1.5, 3, 6, and 12 h after surgery. Monocyte chemotactic protein-1 (MCP-1),
      interleukin (IL)-6 and prostaglandin.E2 (PGE2) were determined. RESULTS: MCP-1
      levels were significantly higher and increased earlier in group II (LC-CO2-NC)
      than in group I (LP-NC) (p< .007). Simultaneously, the increase in the traction
      group was significantly higher (p< .002) than after laparotomy, without
      differences with respect to group II (LC-CO2-NC). When contamination was added,
      there was a significant increase in the three groups (p< .5). The modifications
      in MCP-1 in the LP-C group were statistically significantly greater and appeared
      earlier than those in the traction groups, LC-T-C (p< .002) and LC-CO2-C (p<
      .02). Interleukin 6: the three models showed a significant increase, which
      appeared later in the LP-NC group. Simultaneously, the increase in IL-6 appeared
      earlier and was significantly greater in the LC-T-NC group than in the LP group
      (p< .003), with no differences between the LC-CO2-NC and LC-T-NC groups. There
      was a significant difference between contaminated and uncontaminated groups in
      the LC-CO2 model. The traction model (LC-T-C group) showed a greater increase
      than the LP-C and LC-CO2-C groups (p< .001). PGE2: a significant increase was
      observed in the three models without contamination. However, when contamination
      was added, no differences were observed. CONCLUSION: Pneumoperitoneum with CO2
      provokes a peritoneal response that is qualitatively different from open surgery
      and modifies the response to contamination with a greater increase in MCP-1 and
      IL-6.

PMID- 16426531
TI  - [Risk factors in patients older than 70 years with complicated colorectal
      carcinoma].
AB  - OBJECTIVE: The aim of this study was to analyze the outcome of patients over 70
      years of age who underwent emergency surgery for complicated colorectal
      carcinoma, as well as to identify the factors that might have some influence on
      outcome. PATIENTS AND METHOD: A retrospective study of 54 patients older than 70
      years who underwent emergency surgery for complicated colorectal cancer (42 with
      obstruction and 12 with perforation) between 1991 and 2002 was performed.
      Morbidity and mortality after surgery were studied. To determine prognostic
      factors of morbidity and mortality a multivariate logistic regression analysis
      was also performed. RESULTS: Overall and major morbidity rates were 81.5% and
      42.6%, respectively. The mortality rate was 27.8%. Multivariate analysis revealed
      that perioperative transfusion (p = 0.014) was an independent predictive factor
      of major complications and that a high APACHE II score (p = 0.031) and the
      presence of perforation proximal to the tumor (p = 0.042) independently predicted
      mortality. CONCLUSIONS: Emergency surgery for complicated colorectal carcinoma in
      elderly patients carries elevated morbidity and mortality. The presence of risk
      factors should be taken into account when choosing the most suitable surgical
      technique and evaluating the need for intensive postoperative treatment.

PMID- 16426532
TI  - [Incisional hernia in colorectal cancer surgery. Associated risk factors].
AB  - BACKGROUND: Incisional hernia is one of the most common complications in
      abdominal surgery. The aim of this retrospective study was to examine the true
      incidence of incisional hernia and its risk factors in patients undergoing
      surgery for colorectal cancer. PATIENTS AND METHOD: Two hundred ninety-five
      patients who underwent colorectal cancer surgery between 1993 and 2003 were
      included. The mean follow-up was 37.5 +/- 22 months. RESULTS: Forty-three
      patients developed incisional hernia, representing 14.5% of the total. The
      cumulative percentage of patients developing incisional hernia was 7% at 6
      months, 16% at 1 year, 21% at 2 years and 33% at 5 and 10 years. The only
      significant independent risk factors were chronic obstructive pulmonary disease
      (COPD) (2-year cumulative incidence of incisional hernia of 53%, p = 0.04) and
      abdominal wound infection (2-year cumulative incidence of incisional hernia of
      28%; p = 0.02). CONCLUSION: COPD and abdominal wound infection predispose to
      incisional hernia in colorectal surgery. Abdominal wound infection is the only
      factor over which the surgeon can act preventively by using antibiotic
      prophylaxis and an aseptic technique.

PMID- 16426533
TI  - [Expression of multiple-drug resistant proteins in lung cancer].
AB  - BACKGROUND: Reduction of intracellular drug accumulation plays an important role
      in resistance to chemotherapy in neoplasms. MDR-proteins regulate this cell
      activity. MATERIAL AND METHOD: A total of 147 tumor samples were collected from
      143 patients. Thirty-five samples were obtained by bronchoscopy and 112 were
      surgical specimens. One hundred and one samples from 99 patients were valid for
      the study. The samples underwent cryopreservation and immunohistochemistry for
      detection of three multiple-drug resistant proteins (MDR-proteins): Pgp, Mrp1 and
      Lrp. RESULTS: No proteins were expressed in 16 patients. A single protein was
      expressed in 32 patients: 3 Pgp, 11 Mrp1 and 18 Lrp=0. Two proteins were
      expressed in 34 patients: 24 Pgp and Lrp, 5 Mrp1 and Pgp, 5 Mrp1 and Lrp=0. All
      three proteins were expressed in 17 patients. No differences were observed in
      expression according to age (Pgp [p=0.74], Mrp1 [p=0.95], Lrp [p=0.26]). No
      differences were found according to sex, when both the number (p=0.72) and type
      (p=0.39) of simultaneously expressed proteins were analyzed. No differences were
      observed according to tumoral stage [number (p=0.55), type (p=0.21)] or
      histological grade [number (p=0.59), type (p=0.51)]. The tendency toward
      simultaneous expression of Pgp and Lrp was highly significant (p<0.01). The same
      tendency was not observed in the association between Mrp1 and Lrp (p=0.26).
      CONCLUSIONS: MDR-proteins are frequently expressed in lung cancer. Of the three
      MDR-proteins studied, Lrp was the most frequent. Adenocarcinoma expressed less
      Mrp1 than other histological types. Squamous carcinoma expressed less Lrp than
      adenocarcinomas and large-cell undifferentiated carcinomas. In a considerable
      number of patients, more than two proteins were expressed simultaneously.
      Squamous-cell carcinomas tended to express Pgp, Mrp1 and Lrp simultaneously. Pgp
      was usually expressed in association with Lrp.

PMID- 16426534
TI  - [Unilocular macrocystic serous cystoadenoma of the pancreas].
AB  - The differential diagnosis between macrocystic serous cystoadenoma and mucinous
      cystoadenoma is very difficult but is highly important due to the latter's
      potential for malignant transformation. We present a case of unilocular
      macrocystic serous cystoadenoma. Due to the impossibility of obtaining an
      accurate preoperative diagnosis, all macrocystic unilocular lesions, in an
      appropriate clinical context, must be resected.

PMID- 16426535
TI  - [Traumatic Spigelian hernia. Elective extraperitoneal laparoscopic repair].
AB  - Traumatic Spigelian hernia is rare. These hernias are usually treated in the same
      admission through open surgery. We present a case of Spigelian hernia in a high
      anatomical location following injury, with a cutaneous lesion and preperitoneal
      hematoma. Delayed parietal repair was performed through extraperitoneal
      laparoscopy. Elective laparoscopic repair in this case avoided surgery in an
      injured area, providing clear cosmetic advantages to the patient. We describe a
      modification to the classical approach to facilitate access to high-lying
      Spigelian defects.

PMID- 16426537
TI  - [Cryptorchism].

PMID- 16426536
TI  - [Primary endometriosis of the abdominal wall: an entity to be included in the
      differential diagnosis of abdominal wall masses].
AB  - Endometriosis consists of the presence of extrauterine endometrial tissue. It is
      usually localized in the pelvis, although it can also be found in other sites.
      Cutaneous localization is unusual and the most frequent form appears on scars
      from obstetric or gynecological interventions. It can, however, develop
      spontaneously, especially in umbilical or inguinal areas and can be confused with
      irreducible hernias or granulomas. We present the cases of three patients with
      spontaneous endometriotic nodules of the abdominal wall. The lesions were located
      in the umbilical region in two patients and in the suprapubic area in one. In two
      patients clinical suspicion led to preoperative diagnosis, although diagnosis is
      usually established after histopathological analysis of the surgical specimen.

PMID- 16426538
TI  - [Aggressive angiomyxoma of the pelvis].

PMID- 16426539
TI  - [Peritonitis due to a mesenteric cyst].

PMID- 16426540
TI  - [Gastrocolonic fistula due to gastric adenocarcinoma].

PMID- 16426541
TI  - [Mediastinoscopy in the treatment of recurrent hyperparathyroidism].

PMID- 16426543
TI  - [Nonspecific interstitial pneumonia: epidemiologic and clinical characteristics].
AB  - BACKGROUND AND OBJECTIVES: Patients diagnosed with non-specific interstitial
      pneumonia (NSIP) in 2 hospitals in Barcelona, Spain, were studied to investigate
      the factors that could contribute to the etiology of disease. PATIENTS AND
      METHOD: The consensus diagnostic criteria established by the American Thoracic
      Society/European Respiratory Society were followed. The study included 16
      patients, 10 men (65%) and 6 women (35%), all diagnosed with NSIP by open lung
      biopsy. Patients were questioned on pathological history, occupational or
      environmental exposure, medicinal drug use, contact with birds, and relationship
      with smoking. In addition, were recorded symptoms and physical signs, laboratory
      and respiratory function results, chest X-ray and computerized tomography scan
      features, fiberbronchoscopy findings and open lung biopsy findings. RESULTS:
      Eleven patients (69%) -10 men (100%) and one woman (12%) -were smokers: 4 were
      active and 7 former smokers; 8 (80%) patients had fibrotic NSIP and three (50%)
      had cellular NSIP. Nine (56%) patients had a medication history, and 5 received
      chronic non-steroideal anti-inflammatory drug treatment. Occupational exposure to
      bleach, detergents, and ammonia or chloride products was documented in 6 cases.
      Three patients had contact with manufactured plastic products and isocyanate
      inhalation. CONCLUSIONS: Smoking and medication use were prevalent in NSIP
      patients. Ibuprofen and celecoxib clearly provoked symptoms in one NSIP patient.
      Further studies are required to clarify the role of detergents, isocyanates and
      other occupation-related substances as triggering factors.

PMID- 16426542
TI  - [Prognostic influence of immunological subtypes of T-cell acute lymphoblastic
      leukemia. Study of 81 patients].
AB  - BACKGROUND AND OBJECTIVE: T-cell acute lymphoblastic leukemia (ALL) includes 4
      immunological subtypes: pro-T, pre-T, thymic or cortical and mature. In some
      studies, pro-T and mature subtypes have a poor prognosis. The objective of this
      study was to describe the clinical characteristics, the result of treatment and
      the prognosis of the immunological subtypes of T-cell ALL in 81 adult patients
      included in 2 protocols of the Spanish PETHEMA group (ALL-96 and ALL-93).
      PATIENTS AND METHOD: Between 1993 and 2003, 81 adult patients from 22 Spanish
      hospitals were included in two PETHEMA protocols: ALL-96 for standard-risk
      patients, and ALL-93 for high- risk patients. The main clinical and biological
      parameters as well as the rate of response to treatment, the frequency of
      complete remission , disease free survival and overall survival were compared in
      each T-cell ALL subtype. RESULTS: Of the 64 evaluable patients the distribution
      of the immunological subtypes was: 3 pro-T, 17 pre-T, 22 thymic or cortical and
      22 mature. Patients with mature T-ALL had higher frequency of central nervous
      system involvement and myeloid antigen expression than those of the remaining
      subgroups. Patients with mature T-cell ALL had a slow rate of response to
      treatment in comparison with patients wit pre-T and mature T-cell ALL but this
      did not translate to significant differences in frequency of complete remission
      (77% vs 94%), disease free survival (42% vs 46%) and overall survival (29% vs
      47%). CONCLUSIONS: Although patients with mature T-cell ALL had a slow rate of
      response to treatment and their survival tended to be shorter, in the present
      study there were no statistically significant differences in the prognosis of the
      different subtypes of T-cell ALL.

PMID- 16426544
TI  - [Prevalence of diabetes mellitus in young Asian Indian immigrants in Santa Coloma
      de Gramenet (Spain)].
AB  - BACKGROUND AND OBJECTIVE: There is a general agreement to consider Asian Indian
      subjects, specially those who immigrated to Western countries, as a high-risk
      population to develop type 2 diabetes mellitus (DM2). This could be mainly
      explained by reasons based on the immigration changes, particularly the metabolic
      impact of a westernized diet (environmental hypothesis) or reasons based in the
      presence of tissue resistance to insulin (genetic hypothesis). The aim of the
      study was to estimate the prevalence of DM2 in 3 populations of Asian Indian
      immigrants, non-Asian Indian immigrants and autochthonous subjects. POPULATION
      AND METHOD: An observational multicenter study was performed in 3 primary care
      centers from Santa Coloma de Gramenet (Barcelona, Spain). Subjects from Asian
      Indian, non-Asian Indian and autochthonous origin born between 1948-73 were
      compared. Their DM2 prevalence as well as sociodemographic and clinical data
      among diabetic patients were analyzed. RESULTS: The overall prevalence of DM2 was
      4.6 %. The prevalence of DM2 was higher among Asian Indian immigrants (20.9%, 95%
      CI, 12.1-29.1) compared with autochthonous (3.6%; 95% CI, 2.9-9.3; p < 0.001) and
      non-Asian Indian immigrants (9.7%; 95% CI, 5.3-14.1; p = 0.013). Nevertheless,
      differences between autochthonous and non-Asian Indian immigrants were found (p <
      0.001). Asian Indians subjects had an earlier diagnosis age, especially those
      younger than 44 years, than those of non-Asian Indian immigrants and
      autochthonous groups (p < 0.002 and p < 0.006, respectively). CONCLUSIONS: Taken
      together, these results suggest that young immigrant populations have a higher
      prevalence of DM2 compared with autochthonous ones. Indeed, the prevalence of DM2
      among immigrant Asian Indians represents the highest reported in the European
      Union so far and shows differences with non-Asian Indian immigrants. In spite of
      this, these differences are not totally conclusive in statistical terms; further
      studies are needed to compare both populations.

PMID- 16426545
TI  - [Non-specific interstitial pneumonia].

PMID- 16426546
TI  - [Forensic medicine at the beginning of the 21st century].

PMID- 16426547
TI  - [Observational study of Healthcare Ethics Committees in Catalonia: CEA-CAT Study
      (1). Structure and functioning].

PMID- 16426548
TI  - [Medicolegal institutes, a new management system in forensic medicine in Spain].

PMID- 16426549
TI  - [Pleural effusion and toxocariasis].

PMID- 16426550
TI  - [Myelopathy due to intrathecal chemotherapy in a patient with acute lymphoblastic
      leukemia].

PMID- 16426551
TI  - [Graves-Basedow disease and pleural effusion].

PMID- 16426552
TI  - [Hypersensitivity pneumonitis associated to tramadol].

PMID- 16426553
TI  - [Research in primary health-care. The experience of the group MAPA-MADRID (1993
      2005)].

PMID- 16426554
TI  - [Long QT syndrome and pulmonary embolism].

PMID- 16426555
TI  - [Dysphonia due to oral methylprednisolone. An uncommon adverse side effect].

PMID- 16426556
TI  - Crash costs in the United States by crash geometry.
AB  - MAIN OBJECTIVES: This study was conducted to estimate the costs per crash for
      three police-coded crash severity groupings within 16 selected crash geometry
      types and within two speed limit categories (<or=45 and >or=50 mph). METHODS: We
      merged previously developed costs per victim by abbreviated injury scale (AIS)
      score into U.S. crash data files that scored injuries in both the AIS and police
      coded severity scales to estimate injury costs, then aggregated the estimates
      into costs per crash by maximum injury severity. RESULTS: The most costly crashes
      were non-intersection fatal/disabling injury crashes on a road with a speed limit
      of 50 miles per hour or higher where multiple vehicles crashed head-on or a
      single vehicle struck a human (over 1.69 US dollars and 1.16 million US dollars
      per crash, respectively). The annual cost of police-reported run-off-road
      collisions, which include both rollovers and object impacts, represented 34% of
      total costs. CONCLUSIONS: This paper provides cost estimates useful for
      evaluating roadway countermeasures and for designing vehicles to minimize crash
      harm. It gives unit costs of crashes by type in the coding system used by the
      police. The costs are in an appropriate form for economic analysis of
      countermeasures addressing locally defined problems identified by analyzing
      police crash reports.

PMID- 16426557
TI  - Estimation of incident clearance times using Bayesian Networks approach.
AB  - Effective incident management requires a full understanding of various
      characteristics of incidents to accurately estimate incident durations and to
      help make more efficient decisions to reduce the impact of non-recurring
      congestion due to these accidents. Our goal is thus to have a comprehensive and
      clear description of incident clearance patterns and to represent these patterns
      with formalisms based on Bayesian Networks (BNs). BNs can be used to create
      dynamic incident duration estimation trees that can be extracted in the presence
      of a real incident for which data might only be partially available. This
      capability will enable traffic operators to create case-specific incident
      management strategies in the presence of incomplete information. In this paper,
      we employ a unique database created using incident data collected in Northern
      Virginia. This database is then used to demonstrate the advantages of employing
      BNs as a powerful modeling and analysis tool especially due to their ability to
      consider the stochastic variations of the data and to allow bi-directional
      induction in decision-making. In addition to the presentation of the basic theory
      behind BNs in the context of our problem and the validation of our estimation
      results, the dependency relations among all variables in the estimated BN that
      can be used for both quantitative and qualitative analysis are also discussed in
      detail.

PMID- 16426558
TI  - Explicit and implicit processes in behavioural adaptation to road width.
AB  - The finding that drivers may react to safety interventions in a way that is
      contrary to what was intended is the phenomenon of behavioural adaptation. This
      phenomenon has been demonstrated across various safety interventions and has
      serious implications for road safety programs the world over. The present
      research used a driving simulator to assess behavioural adaptation in drivers'
      speed and lateral displacement in response to manipulations of road width. Of
      interest was whether behavioural adaptation would occur and whether we could
      determine whether it was the result of explicit, conscious decisions or implicit
      perceptual processes. The results supported an implicit, zero perceived risk
      model of behavioural adaptation with reduced speeds on a narrowed road
      accompanied by increased ratings of risk and a marked inability of the
      participants to identify that any change in road width had occurred.

PMID- 16426559
TI  - Risk perception and impulsivity: association with risky behaviors and substance
      abuse disorders.
AB  - Low risk perception and high impulsivity, in conjunction with substance abuse
      disorders, are associated with the occurrence of injury in the general
      population. The study described in this article investigated the association of
      risk perception and impulsivity with risky behaviors (infrequent seat belt use,
      drinking and driving, riding with a drunk driver, binge drinking, and speeding
      for the thrill) among adults with unintentional blunt trauma. Patients (N = 756)
      were assessed for substance abuse disorders and participation in risky behaviors.
      Risk perception and impulsivity were measured by questionnaire. Pearson's chi
      square statistic was used to investigate risk perception, impulsivity, substance
      abuse, and possible confounders relative to risky behaviors. Odds ratios were
      calculated using logistic regression methodology. Univariate results indicated
      that low risk perception and high impulsivity were significant risk factors for
      risky behaviors. After adjustment for confounding factors, low risk perception
      and high impulsivity remained significantly associated with risky behaviors in
      the trauma patient population.

PMID- 16426560
TI  - Older drivers do not have a high crash risk--a replication of low mileage bias.
AB  - The widespread claim that older drivers are overly involved in crashes has
      apparent support from crash data, especially when distance travelled is used as
      the exposure measure. However, independent of age, drivers travelling more
      kilometres will typically have lower crash rates per kilometre than those driving
      fewer kilometres. This paper uses Dutch travel survey data from a large sample of
      respondents to confirm previous research findings concerning the association
      between annual mileages driven and crash involvement. When the crash rates of
      drivers of different ages were compared after being matched for yearly driving
      distance, most drivers aged 75 years and above were indicatively safer than all
      other drivers. Only older drivers travelling less than 3000 km per year (just
      over 10% of all older drivers in the survey) gave any indication of elevated
      crash rates.

PMID- 16426561
TI  - Individual factors affecting the risk of death for rear-seated passengers in road
      crashes.
AB  - We studied the effect of age, gender, use of restraint systems and seat position
      on the risk of death for rear-seated passengers of cars involved in road crashes.
      The data source was the Spanish register of traffic crashes with victims compiled
      by the Government's General Traffic Directorate. Data for crashes recorded from
      1993 to 2002, inclusive, were studied. We used a matched cohort design to analyze
      all 5260 rear-seated passengers in vehicles occupied by two or three rear-seated
      passengers for accidents in which at least one of these passengers was killed.
      Conditional Poisson regression with death as the dependent variable was used. An
      increased risk of death was observed for females and children aged <3 years. For
      passengers aged 25 years and older, the risk increased with age. The use of
      restraint systems and central and right-side seats was associated with a lower
      risk. These results should be considered in research focused on passenger
      fragility and strategies to prevent injury and death.

PMID- 16426562
TI  - [Type I neurofibromatosis, pheochromocytoma and somatostatinoma of the ampulla.
      Literature review].
AB  - Gastrointestinal involvement in Von Recklinghausen's neurofibromatosis (autosomal
      dominant disease) is observed in 25% of patients and is frequently represented by
      duodenal carcinoids. We report a case of somatostatinoma of the ampulla in a 42
      year-old female with neurofibromatosis and pheochromocytoma and show a literature
      review about the association of neurofibromatosis and somatostatinoma. This
      pathological association appears non hasardous and surgical ampullectomy offers a
      good alternative to pancreaticoduodenectomy in localised tumors treatment.

PMID- 16426563
TI  - Relationship between daily fluoride intake from diet and the use of dentifrice
      and human plasma fluoride concentrations.
AB  - The literature contains reports of the relationship between the fluoride
      concentrations in drinking water and human plasma. None of these studies,
      however, documented individual levels of daily fluoride intake, which can vary
      considerably among individuals served by the same water supply. Furthermore,
      while water can be an important source of fluoride, other sources, especially
      fluoridated dentifrices, also contribute substantially. This 2-day study with
      five 25-35-year-old subjects in each of three communities (Bauru, 0.6-0.8 ppm F;
      Domelia, 0.7 ppm F; Floresta, 0.3 ppm F) determined plasma fluoride
      concentrations and fluoride intake from diet and the use of dentifrice which,
      together, approximate total daily fluoride intake. The purposes were to
      determine: (1) the extent to which plasma fluoride concentrations approached
      levels known to affect the quality and quantity of bone; (2) the relationship
      between fluoride intake and plasma concentrations. Plasma was collected at 4-h
      intervals starting at 0800 h and ending at 2000 h each day. Average fluoride
      intakes from diet and the use of dentifrice in the three communities ranged from
      0.16 to 0.82 mg/day and from 0.29 to 3.16 mg/day, respectively. The overall
      average plasma concentrations in the three communities were 0.44, 0.45 and 0.54
      micromol/l (P<0.005). They were directly related to intake from the use of
      dentifrice (P=0.030) and to total intake (P=0.033), but were not related to
      dietary intake (P=0.176). In conclusion, despite fluoride intake from various
      sources, the plasma fluoride concentrations of the study subjects remained at
      levels far below those associated with effects on bone production.

PMID- 16426564
TI  - Age-related changes in hardness and modulus of elasticity of dentine.
AB  - OBJECTIVES: Little knowledge has been clarified about the relationship between
      the morphological and physical changes of dentine during aging. The purpose of
      this study was to clarify the modulus of elasticity and hardness related to the
      morphological changes of dentine by aging using a transmitted light microscope
      (TLM) and a nano-hardness tester (NHT). METHODS: Aged human molars and young
      third molars were used. The dentine morphology was observed under a TLM. The
      hardness and Young's modulus of elasticity related to the morphologic study were
      evaluated with an NHT. RESULTS: The thickness of mantle dentine and globular
      dentine of aged teeth were less than that of young teeth. Transparent dentine was
      observed only underneath the attrition of young teeth. Reactionary tertiary
      dentine formed and a "dark zone" was found at the junction between physiologic
      secondary and reactionary dentine only in aged teeth. At the mantle dentine,
      hardness and modulus of elasticity of aged dentine were higher than those of
      young dentine. The reactionary dentine in aged teeth and newly developed
      secondary dentine in young teeth demonstrated lower modulus of elasticity and
      hardness than those of other circumpulpal dentine. Relatively low modulus of
      elasticity and hardness were observed at the zone between secondary and
      reactionary dentine. CONCLUSIONS: Changes in dentine due to aging resulted in
      transformation of morphological features causing changes to their hardness and
      modulus of elasticity at the explicit areas such as the increase of hardness and
      modulus of elasticity at mantle dentin and the reduction of these properties at
      the "dark zone" that found in aged teeth.

PMID- 16426565
TI  - Correlation of haloperidol levels between submandibular saliva and brain in the
      rat.
AB  - OBJECTIVE: The clinical usefulness of therapeutic drug monitoring (TDM) for
      haloperidol using blood samples has to be validated. Despite the potential
      advantage of TDM using saliva, there are few reports comparing drug levels in
      saliva and blood. Additionally, the relation between haloperidol levels in saliva
      and brain, the target organ of this drug, has not been reported. We compared
      haloperidol levels in rat submandibular saliva, plasma and brain. DESIGN:
      Haloperidol was administered through the femoral vein (0.25 mg/kg). Submandibular
      saliva was collected 30 min after drug administration. To stimulate secretion,
      the chorda (parasympathetic) and superior cervical ganglion (sympathetic) were
      electrically stimulated, and pilocarpine was administered. The concentration of
      haloperidol in saliva, plasma and brain homogenate was determined. RESULTS:
      Haloperidol levels in saliva elicited by any stimuli significantly correlated
      with levels in the brain and plasma. The correlation of haloperidol between
      saliva and brain was higher than that between plasma and brain.
      Immunohistochemistry showed that haloperidol was secreted from striated duct
      cells within the submandibular gland. CONCLUSION: These results suggested that
      haloperidol was specifically secreted from the striated duct system, and that
      salivary drug levels reflect the levels in the brain more precisely than plasma.

PMID- 16426566
TI  - Effect of turpentine-induced fever during the enamel formation of rat incisor.
AB  - OBJECTIVE: Some epidemiological studies have indicated that diseases resulting in
      prolonged and sustained fever, such as exanthemata, respiratory infections and
      otitis media in infantile period or childhood are likely to have a marked
      deleterious effect on enamel formation, but the relationship between fever and
      enamel defects is unknown. The purpose of the present study was to induce a
      persistent high fever and examine the effects on the developing tooth enamel.
      METHODS: Twenty male Wistar rats weighting 140+/-10 g were used in this study.
      For the experimental group, a dose of 2.3 ml/kg steam-distilled turpentine was
      subcutaneously injected into both hind limbs five times at 12h intervals. Control
      rats received 2.3 ml/kg of sterile saline into the same injection site. The
      rectal temperatures of animals were measured at the febrile period. After
      constant periods, the animals were sacrificed, and the mandibular incisors were
      examined by contact microradiography (CMR) and histological observation. RESULTS:
      The febrile state lasted for 57 h and the average temperature rose 1.51 degrees C
      higher than that of the control group. The ground sections, semi-thin and ultra
      thin sections of mandibular incisors were prepared and the enamel was observed.
      The microradiographs showed a radiolucent line along with the incremental line in
      the enamel. Moreover, microscopic examination indicated disorientation of enamel
      prism and crystal-free area within this radiolucent lesion. CONCLUSIONS:
      Persistent high fever pattern was established firmly by the turpentine injections
      and the process of enamel formation was influenced by the febrile period.

PMID- 16426567
TI  - Searching for target sequences by p53 protein is influenced by DNA length.
AB  - One of the most important functions of the tumor suppressor p53 protein is its
      sequence-specific binding to DNA. Using a competition assay on agarose gels we
      found that the p53 consensus sequences in longer DNA fragments are better targets
      than the same sequences in shorter DNAs. Semi-quantitative evaluation of the
      competition experiments showed a correlation between the relative p53-DNA binding
      and the DNA lengths. Our results are consistent with a model of the p53-DNA
      interactions involving one-dimensional migration of the p53 protein along the DNA
      for distances of about 1000 bp while searching for its target sites. Positioning
      of the p53 target in the DNA fragment did not substantially affect the apparent
      p53-DNA binding, suggesting that p53 can slide along the DNA in a bi-directional
      manner. In contrast to full-length p53, the isolated core domain did not show any
      significant correlation between sequence-specific DNA binding and fragment
      length.

PMID- 16426568
TI  - Tumor-specific expression of the novel cytochrome P450 enzyme, CYP2W1.
AB  - A novel human cytochrome P450, CYP2W1, was cloned and expressed heterologously.
      No or very low CYP2W1 mRNA levels were detected in fetal and adult human tissues,
      expression was however seen in 54% of human tumor samples investigated (n=37), in
      particular colon and adrenal tumors. Western blotting also revealed high
      expression of CYP2W1 in some human colon tumors. In rat tissues, CYP2W1 mRNA was
      expressed preferentially in fetal but also in adult colon. The CYP2W1 gene was
      shown to encompass one functional CpG island in the exon 1-intron 1 region which
      was methylated in cell lines lacking CYP2W1 expression, but unmethylated in cells
      expressing CYP2W1. Re-expression of CYP2W1 was seen following demethylation by 5
      Aza-2'-deoxycytidine. Transfection of HEK293 cells with CYP2W1 caused the
      formation of a properly folded enzyme, which was catalytically active with
      arachidonic acid as a substrate. It is concluded that CYP2W1 represents a tumor
      specific P450 isoform with potential importance as a drug target in cancer
      therapy.

PMID- 16426569
TI  - ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced
      by the LPS signal in THP-1 cells.
AB  - LPS induces the production of inflammatory cytokines via the stimulation of Toll
      like receptors. In this study, we demonstrated that a soluble secreted form of
      the ST2 gene product (ST2), a member of the interleukin-1 receptor family,
      suppressed the production of IL-6 in an LPS-stimulated human monocytic leukemia
      cell line, THP-1. Immunofluorescence confocal microscopy revealed the binding of
      ST2 to the surface of the THP-1 cells, in which ST2 led to decreased binding of
      nuclear factor-kappaB to the IL-6 promoter. Furthermore, the degradation of
      IkappaB in the cytoplasm after LPS stimulation was reduced by pretreatment with
      ST2. These results demonstrated that ST2 negatively regulates LPS-induced IL-6
      production via the inhibition of IkappaB degradation in THP-1 cells.

PMID- 16426570
TI  - Impaired growth of pancreatic exocrine cells in transgenic mice expressing human
      activin betaE subunit.
AB  - Activins, TGF-beta superfamily members, have multiple functions in a variety of
      cells and tissues. Recently, additional activin beta subunit genes, betaC and
      betaE, have been identified. To explore the role of activin E, we created
      transgenic mice overexpressing human activin betaE subunit. There were pronounced
      differences in the pancreata of the transgenic animals as compared with their
      wild-type counterparts. Pancreatic weight, expressed relative to total body
      weight, was significantly reduced. Histologically, adipose replacement of acini
      in the exocrine pancreas was observed. There was a significant decrease in the
      number of PCNA-positive cells in the acinar cells, indicating reduced
      proliferation in the exocrine pancreas of the transgenic mice. However,
      quantitative pancreatic morphometry showed that the total number and mass of the
      islets of the transgenic mice were comparable with those of the nontransgenic
      control mice. Our findings suggest a role for activin E in regulating the
      proliferation of pancreatic exocrine cells.

PMID- 16426571
TI  - Disulfiram irreversibly aggregates betaine aldehyde dehydrogenase--a potential
      target for antimicrobial agents against Pseudomonas aeruginosa.
AB  - In the human pathogen Pseudomonas aeruginosa, betaine aldehyde dehydrogenase
      (PaBADH) may play the dual role of assimilating carbon and nitrogen from choline
      or choline precursors--abundant at infection sites--and producing glycine
      betaine, which protects the bacterium against the high-osmolality stress
      prevalent in the infected tissues. This tetrameric enzyme contains four cysteine
      residues per subunit and is a potential drug target. In our search for specific
      inhibitors, we mutated the catalytic Cys286 to alanine and chemically modified
      the recombinant wild-type and the four Cys-->Ala single mutants with thiol
      reagents. The small methyl-methanethiosulfonate inactivated the enzymes without
      affecting their stability while the bulkier dithionitrobenzoic acid (DTNB) and
      bis[diethylthiocarbamyl] disulfide (disulfiram) induced enzyme dissociation--at
      23 degrees C--and irreversible aggregation--at 37 degrees C. Of the four Cys-
      >Ala mutants only C286A retained its tetrameric structure after DTNB or
      disulfiram treatments, suggesting that steric constraints arising upon the
      covalent attachment of a bulky group to C286 resulted in distortion of the
      backbone configuration in the active site region followed by a severe decrease in
      enzyme stability. Since neither NAD(P)H nor betaine aldehyde prevented disulfiram
      induced PaBADH inactivation or aggregation, and reduced glutathione was unable to
      restore the activity of the modified enzyme, we propose that disulfiram could be
      a useful drug to combat infection by P. aeruginosa.

PMID- 16426572
TI  - Preferential inducibility of CYP1A1 and CYP1A2 by TCDD: differential regulation
      in primary human hepatocytes versus transformed human cells.
AB  - Cytochrome P4501A1 (CYP1A1) induction, a marker of aryl hydrocarbon (Ah) receptor
      activation, has been associated with carcinogenicity of the environmental agent
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Consistently, we show that TCDD
      treatment led to induction of CYP1A1 in responsive human cancer cell lines
      including HepG2, LS174T, and MCF-7, as determined by Western blotting and CYP1A
      form-selective R-warfarin 6- and 8-hydroxylation. TCDD, however, preferably
      induced CYP1A2, not CYP1A1, in primary human hepatocytes. Such CYP1A form
      preferred induction at the protein level was apparently uncorrelated with non
      preferred mRNA induction in any cells studied. Moreover, while both genes were up
      regulated by TCDD in primary hepatocytes and HepG2 cells, the induction of CYP1A1
      and CYP1A2 at the mRNA level was distinguishable, indicated by the marked
      differences in activation kinetics and the response to the protein synthesis
      inhibitors, anisomycin and cycloheximide. Furthermore, formation of total
      benzo(a)pyrene (BaP)-DNA adducts was not altered following BaP exposure in TCDD
      treated primary hepatocytes, whereas significantly elevated, in a CYP1A1
      dependent manner, in the treated HepG2 cells. Taken together, our findings,
      demonstrating the complexities of TCDD-associated human Ah receptor function and
      differential regulations of CYP 1A enzymes, suggest clearly the need for caution
      when extrapolating data obtained in cell-based models.

PMID- 16426573
TI  - Application of HSVtk suicide gene to X-SCID gene therapy: ganciclovir treatment
      offsets gene corrected X-SCID B cells.
AB  - Recently, a serious adverse effect of uncontrolled clonal T cell proliferation
      due to insertional mutagenesis of retroviral vector was reported in X-SCID gene
      therapy clinical trial. To offset the side effect, we have incorporated a suicide
      gene into therapeutic retroviral vector for selective elimination of transduced
      cells. In this study, B-cell lines from two X-SCID patients were transduced with
      bicistronic retroviral vector carrying human gamma c chain cDNA and Herpes
      simplex virus thymidine kinase gene. After confirmation of functional
      reconstitution of the gamma c chain, the cells were treated with ganciclovir
      (GCV). The gamma c chain positive cells were eliminated under low concentration
      without cytotoxicity on untransduced cells and have not reappeared at least for 5
      months. Furthermore, the gamma c chain transduced cells were still sensitive to
      GCV after five months. These results demonstrated the efficacy of the suicide
      gene therapy although further in vivo studies are required to assess feasibility
      of this approach in clinical trial.

PMID- 16426574
TI  - Aldosterone-induced abnormal regulation of ENaC and SGK1 in Dahl salt-sensitive
      rat.
AB  - Aldosterone plays a crucial role in controlling mineral balance in our body. The
      mechanism of aldosterone has been reported to elevate renal Na+ reabsorption by
      stimulating expression of epithelial Na+ channel (ENaC) and also activate an ENaC
      regulating protein kinase, serum and glucocorticoid-regulated kinase 1 (SGK1).
      However, it is unknown whether aldosterone shows its stimulatory action on ENaC
      and SGK1 under an abnormal, salt-sensitive hypertensive condition. To clarify
      this point, we studied how aldosterone regulates expression of ENaC and SGK1 in
      Dahl salt-sensitive (DS) rat that shows hypertension with high salt diet. RNA and
      protein were extracted from the kidney 6 h after application of aldosterone (1.5
      mg/kg body weight) subcutaneously injected into adrenalectomized DS and Dahl salt
      resistant (DR) rats. Aldosterone decreased mRNA expression of beta- and gamma
      ENaC in DS rat unlike DR rat, while aldosterone increased alpha-ENaC mRNA
      expression in DS rat similar to DR rat. Further, we found that aldosterone
      elevated SGK1 expression in DR rat, but not in DS rat. These observations
      indicate that ENaC and SGK1 are abnormally regulated by aldosterone in salt
      sensitive hypertensive rats, suggesting that disturbance of the aldosterone
      regulation would be one of factors causing salt-sensitive hypertension.

PMID- 16426575
TI  - YHV-protease dsRNA inhibits YHV replication in Penaeus monodon and prevents
      mortality.
AB  - Yellow head virus infects cultured shrimps and causes severe mortality resulting
      in a great economic loss. Haemolymph injection of dsRNA(pro) corresponding to the
      protease motif of YHV genome resulted in a complete inhibition of YHV
      replication. The effect of dsRNA lasted for at least 5 days. Injecting sequence
      unrelated dsRNA(gfp) or dsRNA(TSV-pol) also resulted in an inhibition of YHV
      replication but at a comparatively much less extent. Shrimp mortality was
      monitored for 10 days when more than 90% shrimps receiving no dsRNA died within 8
      dpi. However, those receiving dsRNA(pro) showed no mortality. A partial mortality
      was observed among the shrimps receiving dsRNA(gfp) or dsRNA(TSV-pol). Thus,
      Penaeus monodon possesses the sequence-specific protection to YHV infection, most
      likely through the RNAi pathway, in addition to sequence-independent protection.
      It gives a new notion that dsRNA induction of antiviral immunity in shrimp goes
      through two pathways, sequence-independent and sequence-dependent.

PMID- 16426576
TI  - CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of
      TSPY protein.
AB  - TSPY (testis-specific protein, Y-encoded) is a member of the greater SET/NAP
      family of molecules with various functions, e.g., in chromatin remodeling,
      regulation of gene expression, and has been implicated to play a role in the
      malignant development of gonadoblastoma, testicular and prostate cancer. Here we
      demonstrate that the C-terminus has a functional role for the nucleo
      cytoplasmatic shuttling of the TSPY protein. Using various combinations of in
      vitro mutagenesis and enhanced green fluorescent protein reporter gene-expression
      experiments we were able to show that while the deletion of C-terminus leads to a
      decreased stability and enhanced degradation of the protein, the selective
      mutation of a C-terminal CK2 phosphorylation site (T300) prevents the TSPY
      protein from entering the nucleus. We conclude that phosphorylation of the (T300)
      residue is a necessary and functional prerequisite for TSPY's transport into the
      nucleus reminding of comparable data from a related Drosophila molecule, NAP1.

PMID- 16426577
TI  - RNA interference in immune cells by use of osmotic delivery of siRNA.
AB  - Delivery of siRNA to immune cells has been one of the major obstacles to
      widespread application of RNAi in the immunology field. Here, we report that
      osmotic delivery of siRNA can be used to silence genes in macrophage RAW264.7
      without incurring either cytotoxic or immunomodulatory activity. We also showed
      usefulness of the osmotic delivery in other types of cells including T cell
      DO11.10. By repeated osmotic delivery of siRNA, long-term gene silencing was
      readily achieved. When TLR4 was disrupted in RAW264.7 cells for 48 h and the
      cells were stimulated with the TLR4 ligand LPS, a significant decrease in
      TNFalpha production was observed. DNA microarray-based gene expression profile
      analysis showed that gene silencing by osmotic delivery of siRNA was target
      specific and the delivery method itself had little influence on overall gene
      expression.

PMID- 16426578
TI  - Anti-viral protein APOBEC3G is induced by interferon-alpha stimulation in human
      hepatocytes.
AB  - Apolipoprotein B mRNA-editing enzyme catalytic-polypeptide 3G (APOBEC3G) is a
      potent inhibitor of infection by a wide range of retroviruses. Although recent
      reports have suggested that human APOBEC3G exerts antiviral activity against
      hepatitis B virus, APOBEC3G expression is normally low in the human liver. To
      clarify the role of APOBEC3G in cellular defenses against hepatitis viruses, the
      regulation of the APOBEC3G expression was investigated in human hepatocytes.
      Endogenous transcripts of nine APOBEC family members were barely detectable in
      quiescent liver cells. However, APOBEC3G was significantly up-regulated in
      response to interferon-alpha (IFN-alpha) stimulation in HepG2, Huh-7, and primary
      human hepatocytes. IFN regulatory factor elements that are important for IFN
      inducible promoter activity were identified 5' upstream from the human APOBEC3G
      gene. Our findings provided the first evidence showing that APOBEC3G is induced
      by IFN stimulation in human hepatocytes and thus could be involved in host
      defense mechanisms directed against hepatitis viruses.

PMID- 16426579
TI  - Expression profile of BDNF-responsive genes during cerebellar granule cell
      development.
AB  - With the aid of microarray and PCR analysis, this investigation sought expression
      profiles of BDNF-regulated genes in cultured mouse cerebellar granule cells and
      addressed their relevance to gene regulation in developing granule cells in vivo.
      Many of the BDNF-upregulated and downregulated genes identified were upregulated
      and downregulated, respectively, during cerebellar development. This
      developmental change was, at least partly, prevented in the TrkB receptor
      deficient cerebellum. The BDNF-upregulated genes were distributed in either
      postmigratory or both premigratory and postmigratory granule cells at postnatal
      day 8 (P8) and were still present in mature granule cells at P21. In contrast,
      the BDNF-downregulated genes were predominantly expressed in premigratory granule
      cells at P8 and disappeared at P21. Furthermore, many of the BDNF-upregulated
      gene products are implicated in signaling cascades of N-methyl-D-aspartate
      receptors and MAP kinase. The results indicate that BDNF signaling plays a
      pivotal role in promoting gene expression in granule cell development and
      maturation.

PMID- 16426580
TI  - MZF1 possesses a repressively regulatory function in ERCC1 expression.
AB  - ERCC1 is a critical gene within the nucleotide excision repair pathway.
      Overexpression of ERCC1 through promoter-mediating transcriptional regulation is
      associated with repair of cisplatin-induced DNA damage and clinical resistance to
      platinum-chemotherapy. Several transcriptional repressors and activators within
      the 5'-flanking region of the ERCC1 gene may be involved in the up-regulation of
      this gene. Minimal sequence within the promoter region required for ERCC1
      transcription was analyzed by CAT assay and demonstrated that the region of -220
      to -110 is essential to constitutive expression of ERCC1 gene in ovarian cancer
      cell line A2780/CP70. A more forward upstream region seems to be responsible for
      cisplatin-induced expression. Study of the functional cis-element in this region
      by electrophoretic mobility shift assay indicates that a MZF1-like site as well
      as an AP1-like site responded in a time-dependent manner to cisplatin stimulation
      with altered binding activities. EMSA with MZF1 ZN1-4 consensus oligonucleotides
      suggests that the MZF1 N-terminal domain of zinc finger cluster may bind to the
      MZF1-like site of the ERCC1 promoter region. MZF1 mRNA in A2780/CP70 cells
      decreased upon cisplatin exposure as analyzed by quantitative PCR, suggesting
      that MZF1 may mediate cisplatin-invoked gene expression in these cells.
      Overexpression of MZF1 repressed the ERCC1 promoter activity as determined in co
      transfection assay, suggesting that MZF1 might be a repressor of ERCC1
      transcription upon cisplatin exposure. In summary, our studies revealed a core
      promoter region and adjacent drug-responsible region within the ERCC1 promoter.
      The drug-responsible region contains cis-elements of activator, AP1 and
      repressor, MZF1. In response to cisplatin treatment, decreased MZF1 and increased
      AP1 binding activities appear to be the leading mechanism of up-regulation of
      ERCC1 expression. Our findings imply potential therapeutic strategies to
      antagonize drug resistant mechanisms in treatment of human ovarian cancer.

PMID- 16426581
TI  - JAK/STAT signal transduction: regulators and implication in hematological
      malignancies.
AB  - Signal transducers and activators of transcription (STATs) comprise a family of
      several transcription factors that are activated by a variety of cytokines,
      hormones and growth factors. STATs are activated through tyrosine
      phosphorylation, mainly by JAK kinases, which lead to their dimerization, nuclear
      translocation and regulation of target genes expression. Stringent mechanisms of
      signal attenuation are essential for insuring appropriate, controlled cellular
      responses. Among them phosphotyrosine phosphatases (SHPs, CD45, PTP1B/TC-PTP),
      protein inhibitors of activated STATs (PIAS) and suppressors of cytokine
      signaling (SOCS) inhibit specific and distinct aspects of cytokine signal
      transduction. SOCS proteins bind through their SH2 domain to phosphotyrosine
      residues in either cytokine receptors or JAK and thus can suppress cytokine
      signaling. Many recent findings indicate that SOCS proteins act, in addition, as
      adaptors that regulate the turnover of certain substrates by interacting with and
      activating an E3 ubiquitin ligase. Thus, SOCS proteins act as negative regulators
      of JAK/STAT pathways and may represent tumour suppressor genes. The discovery of
      oncogenic partner in this signaling pathway, more especially in diverse
      hematologic malignancies support a prominent role of deregulated pathways in the
      pathogenesis of diseases. Fusion proteins implicating the JH1 domain of JAK2 (TEL
      JAK2, BCR-JAK2), leading to deregulated activity of JAK2, have been described as
      the result of translocation. Somatic point mutation in JH2 domain of JAK2
      (JAK2V617F), leading also to constitutive tyrosine phosphorylation of JAK2 and
      its downstream effectors was reported in myeloproliferative disorders.
      Furthermore, silencing of socs-1 and shp-1 expression by gene methylation is
      observed in some cancer cells.

PMID- 16426582
TI  - Idazoxan increases perforant path-evoked EPSP slope paired pulse inhibition and
      reduces perforant path-evoked population spike paired pulse facilitation in rat
      dentate gyrus.
AB  - Norepinephrine, acting via beta-adrenoceptors, enhances the perforant path-evoked
      potential in dentate gyrus. Using systemic idazoxan to increase norepinephrine,
      and paired perforant path pulses to probe early inhibition, previous
      investigators reported that idazoxan increased initial spike amplitude and
      increased somatic feedback inhibition. Here, feedback inhibition was re-examined
      in idazoxan-treated (5 mg/kg) rats under urethane anesthesia. To control for
      initial increased spike amplitude after idazoxan, evoked potentials were matched,
      pre- and post-idazoxan, on initial population spike. Input-output current
      profiles were also compared pre- and post-idazoxan. Saline- and timolol-filled
      micropipettes permitted evaluation of a contribution of local beta-adrenoceptors.
      As previously observed, initial spike amplitude was potentiated by idazoxan.
      Comparable spike potentiation was not seen on the timolol micropipette. Paired
      pulse inhibition of spike amplitude apparently increased, but input-output curve
      comparisons revealed a loss of feedback facilitation rather than an increase in
      feedback inhibition. Initial EPSP slopes were depressed after idazoxan in input
      output curve data. EPSP slope feedback ratios were significantly reduced
      following idazoxan. These data suggest idazoxan has multiple effects on perforant
      path input to the dentate gyrus. Spike potentiation following idazoxan has
      previously been shown to depend on intact norepinephrine input. Here, the
      reduction in spike potentiation on the timolol pipette is consistent with other
      evidence that norepinephrine-mediated potentiation of the perforant path-evoked
      potential is dependent on local beta-adrenoceptor activation. The input-output
      data suggest a decrease in feedback facilitation after idazoxan is likely to
      account for the apparent increase in feedback inhibition previously reported.
      Decreased EPSP slope ratios with similar paired pulse intervals have been
      reported in novel environments. Since exposure to novel environments activates
      locus coeruleus neurons, norepinephrine may mediate the change in EPSP slope
      inhibition reported in awake rats. In summary, these results are consistent with
      the hypothesis that idazoxan potentiates granule cell responses to perforant path
      input in the dentate gyrus via increases in norepinephrine that lead to beta
      adrenoceptor activation, and, further, that idazoxan reduces paired pulse
      feedback spike facilitation and enhances EPSP slope, but not spike, feedback
      inhibition.

PMID- 16426584
TI  - Mismatch negativity (MMN) elicited by changes in phoneme length: a cross
      linguistic study.
AB  - Speech sounds representing different phonetic categories are typically easier to
      discriminate than sounds belonging to the same category. This phenomenon is
      referred to as the phoneme boundary effect. We aimed to determine whether, at
      neural level, this effect is indeed due to crossing the phoneme boundary. The
      mismatch negativity (MMN) brain response was measured for across- and within
      category changes in Finnish phoneme length in native speakers and second-language
      users of Finnish as well as non-Finnish-speaking subjects. The results showed
      that the MMN amplitude was enhanced in the native speakers in comparison with the
      two non-native groups which, in turn, did not differ from each other in MMN
      amplitude. The response pattern to across- and within-category changes, however,
      was the same in all groups regardless of whether or not they had the phoneme
      categories. Thus, the responses could not be determined by crossing the phoneme
      boundary. Rather, the enhancement of MMN amplitude in the native speakers is
      likely to be due to the activation of native-language phonetic prototypes. The
      second-language users, however, did not seem to have automatic access to Finnish
      prototypes.

PMID- 16426583
TI  - Serotonin depletion results in a decrease of the neuronal activation caused by
      rivastigmine in the rat hippocampus.
AB  - Interactions between the serotonergic and cholinergic systems are known to occur
      and are believed to play a role in the mechanism underlying both major depression
      and Alzheimer's disease. On a molecular level, studies suggest that acetylcholine
      (ACh) increases serotonin (5-HT) release through nicotinic receptors located at
      nerve terminals. The aim of the present study was to determine in which areas and
      to what extent 5-HT mediates the neuronal response to ACh release. For this
      purpose, neuronal activity was measured in rats with rivastigmine-induced
      elevated ACh levels after a 95% 5-HT depletion obtained by dosing p
      chlorophenylalanine followed by D,L-fenfluramine. Neuronal activation was
      quantified by stereological measurements of c-Fos immunoreactivity. The brain
      areas examined were medial prefrontal cortex, septum, dorsal hippocampus, and
      dorsal raphe nucleus. Rivastigmine significantly increased c-Fos immunoreactivity
      in medial prefrontal cortex and the hippocampus, but not in the septum and dorsal
      raphe nucleus. 5-HT depletion decreased ACh-induced c-Fos immunoreactivity in the
      dentate gyrus. By contrast, 5-HT depletion had no effect on the ACh-induced
      activity in the other brain areas examined. It is concluded that 5-HT mediates
      part of the ACh-induced hippocampal neuronal activation, possibly mediated via
      locally released 5-HT.

PMID- 16426585
TI  - Developmental increases in hypothalamic neuropeptide Y content with the embryonic
      age of meat- and layer-type chicks.
AB  - We determined central neuropeptide Y (NPY) content of meat- and layer-type chicks
      at embryonic days 7, 14, 20, and at post-hatching day 1. The central NPY was
      detectable at day 7; hypothalamic NPY content developmentally increased with a
      similar pattern but a different level between both types of chicks. These results
      were discussed with respect to feeding behavior early period after hatching.

PMID- 16426586
TI  - Discovery of specific tryptophan hydroxylase in the brain of the beetle Harmonia
      axyridis.
AB  - Rabbit anti-serotonin and mouse monoclonal anti-tryptophan hydroxylase antisera
      were applied on the brain sections of the beetle Harmonia axyridis, butterfly
      Childrena zenobia, moth Antheraea pernyi and ant Camponotus japonicus, using the
      Streptavidin-Peroxidase immunohistochemical method and Colophony-Paraffin
      embedded section technique. Results revealed that all the experimental insects
      showed notable serotonin-like immunoreactivity in the brain. However, only the
      brain sections of the beetle H. axyridis were strongly labeled by mouse
      monoclonal anti-tryptophan hydroxylase antiserum, with the distribution pattern
      matching that of serotonin. These results demonstrate that specific tryptophan
      hydroxylase may exist in the brain of the beetle and likely reflect the diversity
      of serotonin synthetic mechanisms as well as the evolution of aromatic amino acid
      hydroxylase genes.

PMID- 16426587
TI  - L-arginine treatment early in life influences NADPH-diaphorase neurons in visual
      cortex of normal and early-malnourished adult rats.
AB  - This study investigated the effects of repeated l-arginine administration during
      lactation, combined with different suckling conditions, on morphometric
      parameters of primary visual cortex NADPH-diaphorase-positive neurons. Wistar rat
      pups reared in "normal-size litters" or "large litters" (N- and L-conditions;
      litters formed by 6 and 12 pups, respectively) received, from postnatal day 7 to
      28, either arginine (300 mg/kg/day, per gavage) or distilled water (control). At
      90-120 days of life, they were perfused with saline + formaldehyde, and their
      brains were processed for histochemical reaction to reveal NADPH-diaphorase
      positive neurons (malic enzyme indirect method). Compared to the normal-size
      litters, L-rats had lower body weights (P < 0.05), confirming the effectiveness
      of the L-condition in affecting pup development. Concerning NADPH-d
      histochemistry, arginine treatment was associated with increased (P < 0.05)
      density of dendrite varicosities and of dendrite branching frequency, suggesting
      a plastic response of the developing brain to that treatment, even in previously
      malnourished rats. No difference was seen, however, in dendrite orientation,
      total number of neurons, soma area and perimeter, as well as dendrite bifurcation
      points, fractal dimension, and area and volume of dendrite field, suggesting that
      NADPH-d cells are resistant to arginine and nutritional changes, regarding these
      features. Data are considered of interest for studies of synaptic plasticity
      during neural development and its relationships to aggressive agents like
      malnutrition.

PMID- 16426588
TI  - Interhemispheric imbalance during visuospatial attention investigated by
      unilateral and bilateral TMS over human parietal cortices.
AB  - We used single-pulse transcranial magnetic stimulation (TMS) to study
      visuospatial attention. TMS was applied over one hemisphere, or simultaneously
      over both the right and left posterior parietal cortex (PPC), at two different
      interstimulus intervals (ISI) during a visual detection task. Unilateral TMS over
      the right and left PPC, respectively, impaired detection of contralateral
      presented visual stimuli at an ISI of 150 ms. By contrast, simultaneous
      biparietal TMS induced no significant changes in correct stimulus detection. TMS
      at an ISI of 250 ms evoked no changes for magnetic stimulation over either the
      right or the left parietal cortex. These results suggest that both PPC play a
      crucial role at a relatively early stage in the widely distributed brain network
      of visuospatial attention. The abolition of behavioral deficits during
      simultaneous biparietal TMS underlines the common hypothesis that an
      interhemispheric imbalance might underlie the disorders of neglect and extinction
      seen following unilateral brain damage.

PMID- 16426589
TI  - Rip immunoreactivity significantly decreases in the stratum oriens of hippocampal
      CA1 region after transient forebrain ischemia in gerbils.
AB  - In the present study, we observed ischemia-related changes in Rip recognizing the
      promyelinating and myelinating oligodendrocytes in the hippocampus proper after 5
      min of transient forebrain ischemia in gerbils. Rip immunoreactivity was
      significantly altered in the hippocampal CA1 region but not in the CA2/3 region
      after ischemic insult. In the sham-operated group, Rip immunoreactivity was shown
      in the cell bodies and processes of oligodendrocytes in all layers of the
      hippocampus proper. From 15 min to 2 days after ischemic insult, Rip
      immunoreactivity was similar to that of sham-operated group. Three days after
      ischemic insult, Rip-immunoreactive processes were tangled in the stratum oriens
      of the CA1 region, and Rip protein level decreased from this time after ischemia.
      Thereafter, Rip immunoreactivity was decreased time dependently in the CA1
      region. Seven days after ischemic insult, Rip-immunoreactive processes were
      tangled and densely detected in the stratum oriens adjacent to the stratum
      pyramidale. In brief, these results indicate that the significant decrease of Rip
      immunoreactivity in processes in the stratum oriens of the hippocampal CA1 region
      occurs at late time after ischemia, and this decrease in Rip immunoreactivity may
      be associated with delayed neuronal death of CA1 pyramidal cells.

PMID- 16426590
TI  - Pathways of matrix metalloproteinase induction in heart failure: bioactive
      molecules and transcriptional regulation.
AB  - The structural basis for the development of congestive heart failure (CHF) is a
      maladaptive myocardial remodeling process which occurs secondarily to post
      myocardial infarction (MI), hypertensive hypertrophy, or cardiomyopathy. Both
      cellular and extracellular factors are involved in the remodeling process and it
      is the combined action of these factors giving rise to changes in myocardial
      structure which eventually affects function. One component in this remodeling
      process is a family of extracellular matrix degrading enzymes, the matrix
      metalloproteinases or MMPs. Many bioactive molecules such as
      cytokines/chemokines, bioactive peptides, and neurohormones which are operative
      in CHF likely contribute to the induction of MMPs. For example, a specific
      cassette of transcription factors is likely induced with extracellular stimuli in
      the context of CHF which in turn induces MMPs and contributes to the maladaptive
      remodeling process. This review will briefly discuss the biology of the MMP
      family, but will more importantly identify how biological factors active in CHF
      result in the modulation of the MMP family. Understanding how upstream molecules
      are involved in MMP regulation/dysregulation may provide an avenue to develop
      important therapeutic interventions.

PMID- 16426591
TI  - What has been learned about the cardiovascular effects of matrix
      metalloproteinases from mouse models?
AB  - Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible
      for extracellular protein degradation in the cardiovascular system. Originally
      known to play pivotal roles in tissue morphogenesis and wound healing, they have
      been shown to participate in the complex remodeling processes in blood vessels
      and the myocardium. The biological activity of MMPs is regulated at different
      levels: (1) gene expression, (2) activation of precursor proenzyme forms by other
      MMPs or non-MMP proteins, including thrombin and plasmin, (3) complex formation
      with surface and extracellular matrix (ECM) components and (4) inhibition by
      endogenous tissue inhibitors of MMPs, the TIMPs. Murine models with gain or loss
      of gene function of different MMPs and TIMPS have provided a wealth of
      experimental data on their critical role in pathological conditions ranging from
      atherosclerosis, vascular injury, and restenosis to left ventricular function and
      structural remodeling following chronic pressure and volume overload and ischemia
      reperfusion injury.

PMID- 16426592
TI  - Chemopreventive activity of glycyrrhizin on lead acetate mediated hepatic
      oxidative stress and its hyperproliferative activity in Wistar rats.
AB  - Lead is a pervasive environmental pollutant with no beneficial biological role
      and its toxicity continues to be a major health problem due to its interference
      with natural environment. In the present study we have evaluated the
      chemopreventive effect of glycyrrhizin on lead acetate mediated hepatic oxidative
      stress, toxicity and tumor promotion related alterations in rats. Lead acetate
      (100mg/kg bwt., i.p.) enhanced lipid peroxidation with concomitant reduction in
      glutathione, glutathione reductase, glutathione-S-transferase and glutathione
      peroxidase activities. There was an increase in the levels of transaminase
      enzymes and LDH. Lead acetate treatment also enhanced ornithine decarboxylase
      (ODC) activity and [(3)H] thymidine incorporation into hepatic DNA. Pretreatment
      of rats orally with glycyrrhizin (150 and 300 mg/kg bwt., orally) resulted in a
      significant decrease in hepatic microsomal lipid peroxidation (P<0.001) and
      increase in the level of GSH content (P<0.001) and its dependent enzyme. There
      was significant reduction in the levels of SGPT, SGOT and LDH (P<0.001). A
      significant inhibition in ODC activity and DNA synthesis (P<0.001) was also
      observed. On the basis of the above results it can be hypothesized that
      glycyrrhizin is a potent chemopreventive compound against lead acetate mediated
      hepatic oxidative stress, toxicity and tumor promotion related responses in rats.

PMID- 16426593
TI  - Elevated circulating levels of matrix metalloproteinase-9 in type 1 diabetic
      patients with and without retinopathy.
AB  - OBJECTIVE: Tissue expression pattern of matrix metalloproteinases (MMPs) and
      their inhibitors TIMPs indicate that microvascular complications of diabetes
      mellitus are associated with extracellular matrix remodelling. We investigated
      whether circulating levels of MMP-9 and TIMP-1 are altered in diabetic
      retinopathy and whether they might serve as biological markers of ocular
      complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We recruited 47
      type 1 diabetic patients free of vascular complications (n=40) or with
      retinopathy (n=14). Patients with macroangiopathy, neuropathy and nephropathy
      were excluded. A group of nondiabetic control subjects (n=35) was also
      constituted for comparative purposes. Peripheral blood levels of MMP-9 and TIMP-1
      were determined using immunoenzymatic assays. RESULTS: Type 1 diabetic subjects
      exhibited significantly higher circulating levels of both MMP-9 and MMP-9/TIMP-1
      ratio, as well as a tendency to increased serum TIMP-1 levels relative to
      nondiabetic controls (p<0.001). Diabetic patients with retinopathy also displayed
      elevated systemic values of MMP-9 and MMP-9/TIMP-1 ratio when compared to
      patients without retinopathy (p<0.05). Logistic regression analysis identified
      diabetes duration firstly (P<0.01), and MMP-9 serum levels secondly (P<0.01) as
      significant and independent variables associated with the existence of
      retinopathy. CONCLUSIONS: Our data suggest that peripheral blood MMP-9 levels
      might serve as surrogate biomarkers of retinopathy in type 1 diabetic patients
      free of other vascular complications.

PMID- 16426594
TI  - The effect of the APOE polymorphism on HDL-C concentrations depends on the
      cholesterol ester transfer protein gene variation in a Southern European
      population.
AB  - BACKGROUND: Apolipoprotein E (ApoE) locus has consistently shown a significant
      association with low-density lipoprotein cholesterol (LDL-C). However, its impact
      on high-density lipoprotein cholesterol (HDL-C) has been highly controversial
      suggesting that it may be context-dependent. We examined the gene-gene
      interaction between the common ApoE and the CETP polymorphisms in determining HDL
      C concentrations in men and women from the general population. METHODS: 550
      unrelated Caucasian subjects were randomly selected from a Mediterranean Region
      in Spain. Plasma lipids, anthropometric, clinical and lifestyle variables were
      measured. Common ApoE and CETP-TaqIB polymorphisms were determined. RESULTS: We
      have found a gene-gene interaction between and ApoE and the CETP loci in
      determining HDL-C concentrations. Thus, after adjustment for gender, age, body
      mass index, tobacco smoking, alcohol consumption, physical exercise and
      medication, carriers of the E4 allele had lower HDL-C concentrations [mean and
      (standard error): 40.1 (2.6) mg/dL] than E2 subjects [47.7 (3.2) mg/dL; p=0.019],
      and even lower than those of the E3 subjects [44.7 (1.4) mg/dL; p=0.042], only if
      they had the B1B1 genotype. However, mean HDL-C concentrations were higher among
      those with E4 allele carrying the B2 allele at the CETP gene locus [50.5 (2.3)
      mg/dL], and lower among E2 subjects carrying the B2 allele [45.5 (2.6) mg/dL].
      This interaction was observed in both men and women. This gene-gene interaction
      remained statistically significant even after additional adjustment for
      triglycerides. CONCLUSIONS: The effect of the ApoE polymorphism on HDL-C
      concentrations depends on the CETP polymorphism, explaining some of the
      controversial results previously reported for this polymorphism.

PMID- 16426596
TI  - An assay for separating and quantifying four bilirubin fractions in untreated
      human serum using isocratic high-performance liquid chromatography.
AB  - BACKGROUND: The quantification of serum bilirubin fractions has been widely
      performed with both the diazo-method and an enzymatic method; however, the
      accuracy of these methods has not been evaluated because quantitative fractional
      high-performance liquid chromatography (HPLC) reference methods have yet to be
      established. METHODS: Samples were analyzed using HPLC and Shodex Asahipak GS
      320HQ columns. Human serum was subjected to HPLC using direct injection, then
      eluted with acetonitrile: 0.3 mol/l phosphate buffer (pH 6.5) containing 1% Brij
      35 and 0.08% sodium ascorbate (30:70, v/v). RESULTS: Serum bilirubin was
      separated into 4 fractions; retention times of 9.24, 19.92, 24.07, 35.75 min were
      identified as delta bilirubin, bilirubin diglucuronide, bilirubin
      monoglucuronide, and unconjugated bilirubin, respectively. Mean recovery was
      93.0%-99.2%. Total precision of peak retention time, height and area exhibited
      <4.26% variation. Detection range was 3.1 to 348 mg/l. Hemoglobin (6 g/l) and
      immunoglobins produced a small positive interference. beta-carotene (20 mg/l),
      vitamin-B2 (370 microg/l) and B(12) (9.5 microg/l) did not interfere with this
      analysis. Results (n=30) with this method were closely correlated to those by
      Adachi's HPLC method as r=0.9941 to 0.9960, slope=0.88 to 1.27, intercept=-3.2 to
      +4.9, for each fraction. CONCLUSIONS: Since this method was a precise
      quantitative HPLC method for serum bilirubin fractionation, it might be used to
      evaluate the accuracy and the characteristics of various routine methods for
      bilirubin measurement.

PMID- 16426595
TI  - Ribozyme: a clinical tool.
AB  - Catalytic RNAs (ribozymes) are capable of specifically cleaving RNA molecules, a
      property that enables them to act as potential antiviral and anti-cancer agents,
      as well as powerful tools for functional genomic studies. Recently, ribozymes
      have been used successfully to inhibit gene expression in a variety of biological
      systems in vitro and in vivo. Phase I clinical trials using ribozyme gene therapy
      to treat AIDS patients have been conducted. Despite initial success, there are
      many areas that require further investigation. These include stability of
      ribozymes in cells and designing highly active ribozymes in vivo, identification
      of target sequence sites and co-localization of ribozymes and substrates, and
      their delivery to specific tissues and maintenance of its stable long-term
      expression. This review gives a brief introduction to ribozyme structure,
      catalysis and its potential applications in biological systems as therapeutic
      agents.

PMID- 16426597
TI  - Serum IgG4 concentrations in pancreatic and biliary diseases.
AB  - BACKGROUND: Recently, it has been reported that the serum concentration of IgG4,
      a minor component of IgG subclasses, is increased in autoimmune pancreatitis.
      However, data regarding IgG4 concentrations in other pancreatic or biliary
      diseases have been insufficient. METHODS: Serum IgG4 was measured in 116 patients
      with pancreatic or biliary diseases (35 autoimmune pancreatitis, 24 chronic
      pancreatitis except autoimmune pancreatitis, 11 primary sclerosing cholangitis,
      23 pancreatic cancer, 3 islet cell tumor, 2 papilla cancer, 15 bile duct cancer,
      and 3 gallbladder cancer patients). The cut-off concentration of IgG4 was 135
      mg/dl. RESULTS: Increased serum IgG4 was observed in 33 of 35 patients with
      autoimmune pancreatitis, 0 of 24 with chronic pancreatitis, 4 of 11 with primary
      sclerosing cholangitis, 0 of 23 with pancreatic cancer, 0 of 3 with islet cell
      tumor, 0 of 2 with duodenal papilla cancer, 0 of 15 with bile duct cancer and 0
      of 3 with gallbladder cancer patients. CONCLUSIONS: Serum IgG4 was increased in
      autoimmune pancreatitis and was within normal limits for other pancreatic or
      biliary diseases except primary sclerosing cholangitis.

PMID- 16426598
TI  - A decision support system based on support vector machines for diagnosis of the
      heart valve diseases.
AB  - In this paper, a decision support system that classifies the Doppler signals of
      the heart valve to two classes (normal and abnormal) is presented to support the
      cardiologist. The paper uses our previous paper where ANN is used as a
      classifier, as feature extractor from measured Doppler signal. To make this, it
      uses wavelet transforms and short time Fourier transform methods. Before it
      classifies these features, it applies Wavelet entropy to them. In this paper, our
      aim is to develop our previous work by using least-squares support vector machine
      (LS-SVM) classifier instead of ANN. We use LS-SVM and backpropagation artificial
      neural network (BP-ANN) to classify the extracted features. In addition, we use
      receiver operator characteristic (ROC) curves to compare sensitivities and
      specificities of these classifiers and compute the area under the curves.
      Finally, we evaluate two classifiers in all aspects.

PMID- 16426599
TI  - Relation of several antioxidant enzymes to rapid freezing resistance in
      suspension cultured cells from alpine Chorispora bungeana.
AB  - Chorispora bungeana Fisch. & C.A. Mey (Crucifer) is a rare alpine subnival plant
      surviving sudden snowstorms. In this paper, we have attempted to explore possible
      roles of autoxidation rate (AR) and the antioxidant enzymes associated with
      cryoprotective mechanisms in the plant cells. The results showed that when the
      suspension cultures growing at 25 degrees C were suddenly exposed to -8 degrees C
      for 15 days, 2,3,5-triphenyltetrazolium chloride reduction was not affected
      within 9 days and AR remained at a low level in comparison with controls. This
      indicated that the cells maintained considerable amounts of soluble protein and
      the integrity of the cell membranes was intact during the whole freezing test.
      Furthermore, on average, the activity of antioxidant enzymes such as superoxide
      dismutase, dehydroascorbate reductase, ascorbate peroxidase and glutathione
      reductase were prominently enhanced in the freezing-stressed cells. Peroxidase
      activity significantly increased soon after freezing, possibly to make up for the
      early decrease of catalase activity in the cells. Statistical analysis showed
      negative correlations between resistance to rapid freezing and antioxidant enzyme
      activity in the cultured cells after exposure from 25 to -8 degrees C, indicating
      that the reduction of cell viability with freezing activates a combination of
      antioxidant enzymes that results in intact cells. All of these findings suggest a
      synergy between these antioxidant enzymes, leading to a low autoxidation rate
      that contributes to the protection of the cell membranes and plays an important
      role in the resistance of suspension cultured cells of C. bungeana to sudden
      freezing.

PMID- 16426600
TI  - Cryopreservation of Holospora undulata, a bacterial parasite of the ciliate
      Paramecium caudatum.
AB  - We investigated cryopreservation of horizontal transmission stages of Holospora
      undulata, a micronucleus-specific bacterial parasite of Paramecium caudatum.
      Unlike in previous studies on related Holospora species, protocols using glycerol
      as cryoprotectant failed entirely. In contrast, freezing with dimethyl sulfoxide
      (Me2SO) conserved infectiousness of nearly all replicate inocula, although
      infection success was considerably lower than that of fresh inocula. Infection
      probability was enhanced by increasing the Me2SO concentration from 5 to 10%, and
      by freezing at -196 degrees C rather than -80 degrees C. Prolonged storage of up
      to 3 months had no significant effect on the viability of the inocula.

PMID- 16426601
TI  - Depolarization promotes survival of ciliary ganglion neurons by BDNF-dependent
      and -independent mechanisms.
AB  - Membrane activity upregulates brain derived neurotrophic factor (BDNF) expression
      to coordinately support neuronal survival in many systems. In parasympathetic
      ciliary ganglion (CG) neurons, activity mimicked by KCl depolarization provides
      nearly full trophic support. While BDNF has been considered unable to influence
      CG neuronal survival, we now document its expression during CG development and
      show that low concentrations do support survival via high-affinity TrkB
      receptors. Furthermore, a contribution of BDNF to activity-induced trophic
      support was demonstrated by showing that KCl depolarization increased BDNF mRNA
      and protein in, and release of BDNF from, CG neuron cultures. Application of anti
      BDNF blocking antibody or mitogen activated protein kinase (MAPK) kinase
      inhibitor, attenuated depolarization-supported survival, implicating canonical
      BDNF/TrkB signaling. Ca2+-Calmodulin kinase II (CaMKII) was also required since
      its inhibition combined with anti-BDNF or MAPK kinase inhibitor abolished or
      greatly reduced the trophic effects of depolarization. Membrane activity may thus
      support CG neuronal survival both by stimulating release of BDNF that binds high
      affinity TrkB receptors to activate MAPK and by recruiting CaMKII. This mechanism
      could have relevance late in development in vivo as ganglionic transmission and
      the effectiveness of BDNF over other growth factors both increase.

PMID- 16426603
TI  - Induction of cytokines by radioprotective tocopherol analogs.
AB  - Tocols are a family of eight isomers consisting of four tocopherols and four
      tocotrienols that exist in four isomeric forms: alpha (alpha), beta (beta), gamma
      (gamma), and delta (delta). Recently, tocols were found to have important and
      unique biological effects on nutrition and health other than antioxidant
      properties and are, therefore, now receiving increased attention. We have
      demonstrated the radioprotective efficacy of various tocol analogs and some of
      their esters. Three forms of tocols - alpha-tocopherol, alpha-tocopherol
      succinate, and gamma-tocotrienol - significantly protected mice against lethal
      gamma irradiation when administered subcutaneously 24 h before irradiation. The
      radioprotective effects of tocols on survival were associated with peripheral
      blood cell recovery after radiation induced cytopenia. Hematopoietic cytokines
      are known to promote the proliferation and differentiation of blood cell
      progenitors. Therefore, we hypothesized that peripheral blood cell recovery is
      preceded by hematopoietic cytokine induction. To test this hypothesis and compare
      the various radioprotective and non-radioprotective analogs, we measured serum
      cytokines using a sandwich ELISA, Luminex, and cytokine array in mice treated
      with various tocols (alpha-tocopherol succinate, alpha-tocopherol, delta
      tocopherol, gamma- tocopherol, gamma-tocotrienol, and tocopherol acetate). Among
      the serum cytokines measured, ELISA and Luminex studies indicated that alpha
      tocopherol, alpha-tocopherol succinate, and gamma-tocotrienol increased G-CSF
      levels in mice. Alpha-tocopherol succinate was most effective in stimulating G
      CSF. IL-6 was detected by Luminex in sera samples from mice treated with the
      above three analogs. The results of the cytokine array suggest that other
      cytokines and chemokines in addition to G-CSF and IL-6 are induced. Since G-CSF,
      IL-6, and certain chemokines are important hematopoietic factors, these results
      support our hypothesis that the protection of mice from radiation-induced
      hematopoietic death is mediated by cytokines and chemokines. These studies may
      indicate that alpha-tocopherol succinate can be used as an adjunct in cancer
      chemotherapy, where neutropenia is a serious problem with threatening infectious
      complications.

PMID- 16426602
TI  - A requirement for NF-protocadherin and TAF1/Set in cell adhesion and neural tube
      formation.
AB  - Neurulation in vertebrates is an intricate process requiring extensive
      alterations in cell contacts and cellular morphologies as the cells in the neural
      ectoderm shape and form the neural folds and neural tube. Despite these complex
      interactions, little is known concerning the molecules that mediate cell adhesion
      within the embryonic neural plate and neural folds. Here, we demonstrate the
      requirement for NF-protocadherin (NFPC) and its cytosolic partner TAF1/Set for
      proper neurulation in Xenopus. Both NFPC and TAF1 function in cell-cell adhesion
      in the neural ectoderm, and disruptions in either NFPC or TAF1 result in a
      failure of the neural tube to close. This neural tube defect can be attributed to
      a lack of proper organization of the cells in the dorsal neural folds, manifested
      by a loss in the columnar epithelial morphology and apical localization of F
      actin. However, the epidermal ectoderm is still able to migrate and cover the
      open neural tube, indicating that the fusions of the neural tube and epidermis
      are separate events. These studies demonstrate that NFPC and TAF1 function to
      maintain proper cell-cell interactions within the neural folds and suggest that
      NFPC and TAF1 participate in novel adhesive mechanisms that contribute to the
      final events of vertebrate neurulation.

PMID- 16426604
TI  - Differential neurogenic potential of progenitor cells in dentate gyrus and CA1
      sector of the postischemic adult monkey hippocampus.
AB  - The adult mammalian hippocampus contains neural progenitor cells capable of
      neuronal production under normal conditions. Cerebral injuries such as ischemia
      lead to their upregulation in rodent models, resulting in neurogenesis in the
      dentate gyrus (DG) and CA1 sector. The adult primate DG also has neurogenic
      potential under normal conditions, and we have previously shown that transient
      global cerebral ischemia increases progenitor cell proliferation in monkey DG,
      with a peak in the second postischemic week. Until now, however, long-term
      effects of ischemia on adult-generated cells in the primate hippocampus have not
      been described. We show here that nearly 15% of the adult-generated cells in
      monkey DG express neuronal features in the dentate granule layer for at least 79
      days after the insult. At the same time, most adult-born cells in DG sustained
      their localization in the subgranular zone with an immature progenitor phenotype.
      In contrast to DG, no signs of neuronal production were observed in the
      postischemic hippocampus proper and in particular in the CA1 sector, where the
      newly-born cells were consistently of glial phenotype. Proliferating progenitors
      in DG but not in the subventricular zone adjacent to CA1 expressed the pro-neural
      transcription factors Emx2, Pax6 and Ngn2. Taken together, these results suggest
      that the neuronal production in adult monkey hippocampus after global brain
      ischemia is limited to DG and does not occur in the hippocampus proper. The
      present data implicate the proteins Emx2, Pax6 and Ngn2 as putative molecular
      signals controlling the fate of progenitor cells of the adult primate
      hippocampus.

PMID- 16426605
TI  - Unique regulation of thyroid hormone metabolism during fasting in the house musk
      shrew (Suncus murinus, Insectivora: Soricidae).
AB  - The active hormone, 3,3',5-triiodothyronine (T3) is derived from thyroxine (T4)
      by the action of iodothyronine 5'-deiodinases (5'-D). By now two types of 5'-D
      have been identified; Type 1 (D1) and type 2 (D2). A relative contribution of
      these isotypes to the circulating T3 levels in the human remains to be determined
      whereas a number of reports indicate that, under physiological conditions, D1
      plays a major role in maintaining circulating T3 levels in rodents. In both human
      and rodents, sickness and starvation reduce serum T3 concentration mainly through
      decrease in D1 activity. Recently, we found that the house musk shrew (Suncus
      murinus, Insectivora: Soricidae) has a different tissue distribution of D1
      activity. Because compared to rodents D1 activity in the shrew was found only in
      liver at a much reduced level, D2 rather than D1 may play a role in the
      maintenance of serum T3. Therefore, we questioned how D1 and D2 activities change
      in fasted shrews and how these changes affect circulating thyroid hormone levels.
      We thus starved shrews for 24, 48 or 72 h and measured changes in serum
      concentration of T3, T4, and 3,3',5'-triiodothyronine (reverse T3, rT3) and D1
      activities as well as its mRNA expression in liver. D2 activities were also
      measured in brown adipose tissue (BAT) and cerebral cortex of shrews. Unlike in
      human and rodents, T3 levels in shrews remained constant during fasting while T4
      levels tended to decrease, resulting in an increase in its T3/T4 ratio. On the
      other hand, changes in rT3 levels were similar to those in human and rodents,
      being elevated with fasting. D1 mRNA and its activity were significantly reduced
      in the liver whereas D2 activities in BAT and cerebral cortex were increased by
      fasting. These results indicated that fasting in shrews also reduced hepatic D1
      activity but it did not affect circulating T3 levels. The increased T3/T4 ratio
      together with increased D2 activity in BAT and cerebral cortex with fasting
      suggest that D2 rather than D1 is responsible for the maintenance of T3 levels in
      the house musk shrew.

PMID- 16426606
TI  - Regulation of behavioral responses by corticotropin-releasing factor.
AB  - In the wild, animals survive by responding to perceived threats with adaptive and
      appropriate changes in their behaviors and physiological states. The exact nature
      of these responses depends on species-specific factors plus the external context
      and internal physiological states associated with the stressful condition. The
      neuroendocrine mechanisms that control context-dependent stress responses are
      poorly understood for most animals, but some progress has been made recently.
      Corticotropin-releasing factor (CRF) plays an important role in mediating
      neuroendocrine, autonomic, and behavioral responses to stress. Across many
      vertebrate taxa, CRF not only stimulates the HPA axis by increasing the secretion
      of ACTH and glucocorticoid hormones, but also acts centrally by modifying
      neurotransmitter systems and behaviors. CRF or one of several CRF-related
      neuropeptides acts to stimulate locomotor activity during periods of acute
      stress. This behavioral activation consists of anxiety-related non-ambulatory
      motor activity, ambulatory locomotion, or swimming depending on the species and
      context. CRF-related neuropeptides increase swimming behaviors in amphibians and
      fish, apparently by activating brainstem serotonergic systems because the
      administration of fluoxetine (a selective serotonin re-uptake inhibitor) greatly
      enhances CRF-induced locomotor activity. Thus, our working model is that CRF, in
      part via interactions with brainstem serotonergic systems, modulates context
      dependent behavioral responses to perceived threats, including both anxiety
      related risk assessment behaviors and fight-or-flight locomotor responses.

PMID- 16426607
TI  - Circadian rhythms of prolactin secretion in neonatal female rabbits after acute
      separation from their mothers.
AB  - Newborn rabbits (Oryctolagus cuniculus) are only nursed for 3-5 min every 24 h
      and show a circadian increase in activity in anticipation of nursing. The
      objective of this study was to determine, in neonatal female rabbits after acute
      separation from the doe for 48 h, the changes in 24-h rhythms of plasma prolactin
      and median eminence and anterior pituitary concentration of dopamine (DA) and
      serotonin (5HT). In addition, median eminence concentration of the excitatory
      amino acid transmitters glutamate (GLU) and aspartate (ASP) and of the inhibitory
      amino acid transmitters gamma-aminobutyric acid (GABA) and taurine (TAU) was
      measured. A significant 21% increase of circulating prolactin occurred in
      isolated pups. In controls pups, plasma prolactin levels showed two peaks, during
      the first half of the light phase and at the beginning of the scotophase,
      respectively. In the isolated pups, a phase advance of about 4 h occurred for the
      two prolactin peaks. Hemicircadian changes of median eminence DA were found in
      controls, whereas a single daily peak (at 17:00 h) was found in the separated
      pups. Plasma prolactin and median eminence DA correlated significantly and
      inversely in the control group only. Pituitary DA content exhibited a single peak
      in controls and a hemicircadian pattern in isolated pups. Plasma prolactin and
      pituitary DA correlated significantly in isolated pups only 00000. Pup isolation
      decreased median eminence 5HT levels, augmented pituitary 5HT levels and
      disrupted their 24 h rhythmicity. Circulating prolactin correlated inversely with
      median eminence 5HT and directly with adenohypophysial 5HT only in controls.
      Isolation of pups generally modified the 24 h pattern of median eminence
      excitatory and inhibitory amino acid content by causing a prominent decrease at
      the beginning of the light phase. The results indicate that circadian rhythmicity
      of prolactin secretory mechanisms in female rabbit pups is significantly affected
      by pup's isolation from the doe.

PMID- 16426609
TI  - Multiple natriuretic peptides coexist in the most primitive extant ray-finned
      fish, bichir Polypterus endlicheri.
AB  - Natriuretic peptides (NPs) have diversified from a single NP in cyclostomes and
      elasmobranchs to multiple NPs in ray-finned fishes where ANP, BNP, VNP, and/or up
      to four CNPs (CNP-1, 2, 3, and/or 4) have been identified. To trace the
      evolutionary diversification of NPs in fishes, we analyzed the bichir (Polypterus
      endlicheri), believed to be the most primitive extant ray-finned fish, for the
      presence of any NPs by a PCR-based method using primers that amplify all NP cDNAs
      identified to date. We have cloned cDNAs encoding ANP, BNP, VNP from the heart
      and three CNPs (CNP-1, 3, and 4) from the brain. An extensive search for CNP-2
      from the brain was not successful. The C-terminus of bichir ANP presented an
      amidation signal as in ray-finned fish ANP. The bichir BNP mRNA had AUUUA repeats
      in the 3'-untranslated region as observed in all BNP cDNAs of vertebrates. The
      bichir VNP had a long C-terminal 'tail' sequence extending from the
      intramolecular ring as does teleost VNP. The three bichir CNPs are structurally
      similar to each teleost counterpart and are grouped after molecular phylogenetic
      analyses. ANP was most abundantly expressed in the atrium, BNP in the ventricle,
      and VNP was expressed in both atrium and ventricle. The three CNPs are most
      abundantly expressed in the brain, and CNP-4 transcripts were found in small
      amounts in the ventricle and kidney. Taken together, it is clear that all major
      NPs exist prior to the whole genome duplication that occurred in the teleost
      lineage. Furthermore, this is the first observation that CNP-3, ANP, BNP, and
      VNP, whose genes are colocalized in the same chromosome, coexist in a single fish
      species including teleosts, thereby confirming that CNP-3 is not an ortholog of
      VNP, and that ANP, BNP, and VNP genes were generated by tandem duplication from
      the CNP-3 gene.

PMID- 16426608
TI  - Molecular cloning of a putative receptor guanylyl cyclase from Y-organs of the
      blue crab, Callinectes sapidus.
AB  - Crustacean molt-inhibiting hormone (MIH), a polypeptide produced by
      neurosecretory cells in eyestalk ganglia, suppresses the synthesis of ecdysteroid
      molting hormones by paired Y-organs. Data from several sources indicate the
      effects of MIH are mediated, at least in part, by a cGMP second messenger. Based
      on these and related findings, our working hypothesis is that the MIH receptor is
      a receptor guanylyl cyclase (rGC). In studies reported here, we used a PCR-based
      cloning strategy (RT-PCR followed by 5'- and 3'-RACE) to clone from blue crab
      (Callinectes sapidus) Y-organs a cDNA (CsGC-YO1) encoding a putative rGC. DNA
      sequence analysis revealed a 3807 base pair open reading frame encoding a 56
      residue signal peptide and a 1213 residue rGC. Analysis of the deduced amino acid
      sequence showed that CsGC-YO1 contains the signature domains characteristic of
      rGCs, including an extracellular ligand-binding domain, a single transmembrane
      domain, a kinase-like domain, a dimerization domain, and a cyclase catalytic
      domain. CsGC-YO1 is most closely related to an rGC from the crayfish, Procambarus
      claikii (PcGC-M2, 58.4% identity), and rGCs from three insect species (33.1-37.5%
      identity). Conserved cysteine residues are similarly distributed in the
      extracellular domains of CsGC-YO1, PcGC-M2, and the three insect rGCs. RT-PCR
      revealed the CsGC-YO1 transcript is expressed in Y-organs and several other
      tissues. While other interpretations of the data are possible, our working
      hypothesis is that the cloned cDNA encodes an MIH receptor.

PMID- 16426610
TI  - Plasma levels of androgens and cortisol in relation to breeding behavior in
      parental male bluegill sunfish, Lepomis macrochirus.
AB  - Like many teleosts, male bluegill sunfish (Lepomis macrochirus) provide sole
      parental care. To understand some of the proximate costs of parental care, we
      measured body condition and plasma levels of testosterone (T), 11
      ketotestosterone (11KT) and cortisol in nesting bluegill males during pre
      spawning, spawning and parental care stages. T and 11KT were at their highest
      mean levels during the pre-spawning period and decreased to lower levels early
      during the parental care period before rising again when the eggs hatched.
      Cortisol levels fluctuated across the breeding stages, but there was a noticeable
      increase from low levels on the day of spawning during the first 2 days of
      parental care when egg fanning is most intense. Levels of all hormones varied
      considerably among males, with androgen levels often correlating positively with
      a male's body condition. We also demonstrate, using a brood reduction experiment
      and repeated sampling of known individuals, that the presence of eggs affects
      hormone levels shortly after eggs hatch. Parental males in better body condition
      had higher levels of androgens during parental care. Males that were known to
      renest later in the season also had higher androgen levels and were in better
      body condition during the first nesting bout than males only known to have nested
      once. However, circulating levels of cortisol did not differ significantly
      between these groups. We discuss our findings in the context of proximate and
      ultimate costs of parental care and propose several reasons why elevated androgen
      levels may not be as incompatible with the expression of paternal care in male
      teleosts, as compared with avian and mammalian fathers.

PMID- 16426611
TI  - Intracapsular hip fractures in end-stage renal failure.
AB  - Patients with end-stage renal failure (ESRF) have metabolic bone disease. This
      increases the risk of femoral neck fracture and increases the risk of
      complications associated with fracture fixation such as non-union and avascular
      necrosis (AVN). We report the results of treatment in a consecutive series of 15
      intracapsular fractures of the hip occurring in 13 patients with ESRF over a 5
      year period. Six intracapsular hip fractures (of which five were undisplaced)
      were treated by internal fixation. Five out of these six (mean=83.3%) required
      conversion to total hip arthroplasty because of non-union or AVN. In all six of
      these patients, internal fixation was considered adequate post operatively. Of
      the remaining nine intracapsular hip fractures treated by hemiarthroplasty, only
      one required conversion to total hip arthroplasty because of stem subsidence
      (mean=11%). The difference in the revision rate for the two groups i.e. primary
      fixation versus primary hemiarthroplasty was statistically significant (p
      value=0.01). The six patients with undisplaced intracapsular fractures treated by
      internal fixation required a total of 14 major operations, at an average rate
      (including initial fracture fixation and revision surgery) of 2.3 per patient.
      The 9 displaced fractures treated by hemiarthroplasty required just 10 operations
      in total, at an average rate of 1.1 per patient. (The difference was significant;
      p-value=0.006.) The 1-year mortality in the whole group (13 patients with 15
      fractures) was 44.4%. We suggest that patients with ESRF with an intracapsular
      fracture of the neck of femur should be treated by replacement arthroplasty
      irrespective of femoral head displacement because of the high risk of revision
      surgery associated with internal fixation.

PMID- 16426612
TI  - Interprosthetic dislocations of the Charnley/Hastings hemiarthroplasty--report of
      11 cases in 350 consecutive patients.
AB  - We report 11 cases of interprosthetic dislocation of the Charnley/Hastings
      hemiarthroplasty in a retrospective study of 350 consecutive patients treated for
      an acute femoral neck fracture. We found a total of 14 dislocations (4.0%), 11
      were interprosthetic. The median age of the 350 patients was 79 (36-99) years and
      the median age of the 11 patients with an interprosthetic dislocation was 85
      years (82-94). The median time from surgery to radiologically acknowledged
      dislocation was 18 (4-64) days. These interprosthetic dislocations may be caused
      by either an assembly mistake perioperatively, by maximum angulation and
      impingement between the components, or by trauma.

PMID- 16426613
TI  - The use of graft materials in vaginal pelvic floor surgery.
AB  - OBJECTIVE: To review recent literature on graft materials used in vaginal pelvic
      floor surgery. METHODS: A Pubmed-search ("anterior vaginal wall" or "cystocele"),
      ("posterior vaginal wall" or "rectocele") and ("vaginal vault" or "pelvic
      prolapse") and ("mesh" or "erosion" or "graft" or "synthetic") from 1995 to 2005
      was performed; recent reviews [Birch C. The use of prosthetics in pelvic
      reconstructive surgery. Best Pract Res Clin Obstet Gynaecol 2005;19:979-91 [1];
      Maher C, Baessler K. Surgical management of anterior vaginal wall prolapse: an
      evidence-based literature review. Int Urogynecol J Pelvic Floor Dysfunct 2005
      (May 25) [Electronic Publication] [2]; Maher C, Baessler K. Surgical management
      of posterior vaginal wall prolapse: an evidence-based literature review. Int
      Urogynecol J Pelvic Floor Dysfunct 2006;17:84-8 [3]; Altman D, Mellgren A,
      Zetterstrom J. Rectocele repair using biomaterial augmentation: current
      documentation and clinical experience. Obstet Gynecol Surv 2005;60:753-60 [4]
      were added. RESULT: There are few prospective randomized trials that prove the
      benefit of implanting grafts in vaginal pelvic floor surgery. Many articles are
      retrospective case series with small sample sizes or incomplete outcome
      variables. Serious complications such as erosions are often not mentioned.
      Inconsistent or unclear criteria for anatomic cure make it difficult to compare
      outcomes. Quality of life issues such as dyspareunia, urinary or bowel symptoms
      are often ignored. CONCLUSION: Due to a lack of well-designed prospective
      randomized trials, recommendations for using graft materials in vaginal
      reconstructive surgery cannot be made. At this time, grafts should have limited
      use in a carefully selected patient population.

PMID- 16426614
TI  - Jordanian patients' perception of stressors in critical care units: a
      questionnaire survey.
AB  - BACKGROUND: Critical care units' CCUs environment has been regarded as a leading
      stressor because of the complex nature of patient's health problems that require
      an extensive use of very sophisticated technology. Multiple and complex care
      predominates in CCUs have been described by patients to be stressful and
      emotionally demanding. RATIONALE: Number of CCUs in Jordan has been increasing
      and so does the advanced technology, which calls for adaptability in dealing with
      unit stressors as they affect patient recovery and rehabilitation. OBJECTIVES: To
      identify the principal physical and psychological stressors as perceived by
      Jordanian patients in CCUs and to examine the effects of selected patients'
      characteristics on their perception of stressors. METHODS: In this cross
      sectional study, data was collected from 165 patients, 2-3 days after being
      discharged from CCUs in two Jordanian governmental hospitals. A structured
      interview guide including the Intensive Care Unit Environmental Stressor Scale
      was used. RESULTS: Having tubes in nose or mouth, being in pain, not able to
      sleep and hearing the buzzers and alarms from the machinery, being thirsty, and
      not being in control of your-self were considered by patients as the main
      stressors. Psychological stressors were the least stressful items identified by
      patients. Marital status, educational level, age, and income were the most
      significant characteristics which affected patients' perception of stressors.
      CONCLUSIONS: The findings suggest that single and older patients with low income
      and low education experience more difficulties than their counterparts. Nurses
      must utilize more effective communication techniques and interventions to relieve
      patients' pain, and provide an atmosphere in which rest is possible, with less
      light, noise, and the fewest possible interruptions. Although the results of this
      study indicate the need to provide the best possible physical care, it is equally
      important to give adequate attention to patients' and families' psychological
      aspects.

PMID- 16426615
TI  - Provision of individualised care improves hospital patient outcomes: an
      explanatory model using LISREL.
AB  - BACKGROUND: Previous studies propose the efficacy of individualised care for
      hospital patients. Individualised care and proposed correlates have not been
      tested by means of a single multivariate analyses simultaneously. OBJECTIVES: The
      aim of this study is to examine predicted relationships between individualised
      care and patient satisfaction, patient autonomy and health-related quality of
      life. DESIGN: A cross-sectional correlational survey. SETTINGS: This study was
      carried out in six acute hospitals in Southern Finland. PARTICIPANTS: A sample of
      861 (response rate 84%) pre-discharged hospitalised adult patients were recruited
      from surgical, gynaecological and internal medicine units. METHODS: A
      correlational survey design was used to investigate to complete a battery of
      instruments measuring individualised care (the ICS), patient satisfaction with
      nursing care (the PSS), patient autonomy and perceived health-related quality of
      life (the 15D). The data from these instruments were used to test the proposed
      model using LISREL implementing the Maximum Likelihood estimation procedure.
      RESULTS: The findings support the proposed model linking individualised nursing
      care directly to the positive patient outcomes defined. The initial model,
      permitting all possible covariances, showed a good fit between the variables.
      Independent variables, supported individuality through nursing interventions (ICS
      A) and perception of individuality in their own care (ICS-B) accounted for 58% of
      the variance in the frequency of individualised care. Individualised care
      explained the variance on the dependent variables patient satisfaction and
      patient autonomy. A low but significant association was also found between
      individualised care and perceived health-related quality of life. CONCLUSIONS:
      The results of this study highlight the contribution of individualised nursing
      care to positive patient outcomes, such as patient satisfaction, patient autonomy
      and perceived health-related quality of life. Not only clinically important, this
      model also has implications for further research into individualised care and its
      relationship with positive patient outcomes.

PMID- 16426616
TI  - Setting the space for sex: architecture, desire and health issues in gay
      bathhouses.
AB  - This aim of this study was to describe and compare the physical design, as well
      as the atmosphere of urban gay bathhouses, and reflect on how desire operates
      within these premises when it intersects with the bathhouse environment and
      health imperatives. Three bathhouses were studied for a total of 147 h of
      observation. Men's desire for other men has created a landscape of spaces (real
      and virtual) where sex takes place in parks, alleys, restrooms, rest stops, adult
      theatres, video arcades, bookstores, bars, gay bathhouses and finally, the
      Internet. Although the Internet is perceived as an easy way for encountering
      sexual partners, gay bathhouses remain the most popular and convenient way, for
      men having sex with men to meet for regular or casual sex. This paper presents
      the descriptive results of an ethnographic nursing study that took place in three
      gay bathhouses located in two Canadian metropolitan areas. Gay bathhouses offer
      patrons a space within which a wide range of interactions, sensations and
      pleasure can be experienced. This paper highlights the specific features of three
      gay bathhouses, compares settings according to their specific architectural
      features and related sexual activities, and finally, proposes some changes in
      light of certain health issues.

PMID- 16426617
TI  - Registered nurses' education and their views on competence development in
      municipal elderly care in Sweden: a questionnaire survey.
AB  - BACKGROUND: Recent changes of municipal elderly care in Sweden have resulted in
      that persons 65 years and older, previously nursed in hospital facilities, are
      now being cared for in the municipality. This change has had a significant impact
      on the work situation of registered nurses (RNs) and calls for appropriate
      educational preparation to enable RNs to undertake their new roles effectively.
      AIM: The main focus was to describe RNs' education and their view of competence
      development in municipal elderly care. Another aim was to compare RNs working
      solely in dementia care (DC) with those working in general elder care (GC) of
      older persons with diverse diagnoses. DESIGN: A non-experimental, descriptive
      design with a survey research approach was used. SETTINGS: Sixty special housing
      with subunits including those offering daytime activities in a large city in the
      middle of Sweden. PARTICIPANTS: The number of participating RNs was a total of
      213, with a response rate of 62.3%. Of the 213 RNs, 95 (44.6%) worked in DC, and
      118 (55.4%) in GC. METHOD: A questionnaire survey. RESULTS: The findings showed
      that RNs possessed a broad range of competence. The majority lacked a bachelor's
      degree in nursing. Few had adequate specialist competence. RNs' in DC wanted to
      invest more in competence development whereas RNs in GC were more motivated to
      attain greater authority in the making of important decisions and to seek another
      position. CONCLUSION: An important future prospect is to develop the competence
      of RNs in elderly care. In order to ensure high quality and security in elderly
      care, it is also essential to increase the number of RNs with specialist
      competence.

PMID- 16426618
TI  - Family presence during CPR: a study of the experiences and opinions of Turkish
      critical care nurses.
AB  - BACKGROUND: The concern over family witnessed cardiopulmonary resuscitation has
      been a frequent topic of debate in many countries. OBJECTIVES: The aim of this
      descriptive study is determine the experiences and opinions of Turkish critical
      care nurses about family presence during cardiopulmonary resuscitation and to
      bring this topic into the critical care and the public limelight in Turkey.
      METHODS: Study population consisted of critical care nursing staff at four
      hospitals affiliated with the Ministry of Health, three hospitals affiliated with
      universities and three hospitals affiliated with Social Security Agency
      Hospitals. A total of 409 eligible critical care nurses were surveyed using a
      questionnaire which is consisted of 43 items under 3 areas of inquiry. RESULTS:
      None of the hospitals that participated in this study had a protocol or policy
      regarding family witnessed resuscitation. More than half of the sample population
      had no experience of family presence during cardiopulmonary resuscitation and
      none of the respondents had ever invited family members to the resuscitation
      room. A majority of the nurses did not agree that it was necessary for family
      members to be with their patient and did not want family members in resuscitation
      room. In addition, most of the nurses were concerned about the violation of
      patient confidentiality, had concerns that untrained family members would not
      understand CPR treatments, would consider them offensive and thereby argue with
      the resuscitation team. The nurses expressed their concern that witnessing
      resuscitation would cause long lasting adverse emotional effects on the family
      members. CONCLUSION: This study reveals that critical care nurses in Turkey are
      not familiar with the concept of family presence during cardiopulmonary
      resuscitation. In view of the increasing evidence from international studies
      about the value of family presence during cardiopulmonary resuscitation we
      recommend educational program about this issue and policy changes are required
      within the hospitals to enhance critical care in Turkey.

PMID- 16426619
TI  - Gas chromatographic peak identification for polybrominated diphenyl ethers under
      different temperature programs.
AB  - A method has been developed for gas chromatographic peak recognition of
      polybrominated diphenyl ethers (PBDEs) under different temperature programs. On
      the basis of an identification database of retention parameters (A, B values) of
      gas chromatography and retention times of the selected internal standards, the
      retention times of BDEs can be accurately estimated. In comparison with the
      experimental retention values, the predicted retention times have been proved to
      be very accurate. In addition, owing to only a part of BDE analytical standards
      are available, using 40 BDEs as a training set, the quantitative relationship
      between retention parameters of BDEs and molecular connectivity indexes has been
      found. The correlation coefficients are greater than 0.997. The A, B values of
      all the remaining 169 BDE congeners have been predicted.

PMID- 16426620
TI  - Fractionation of polyphenols in hawthorn into polymeric procyanidins, phenolic
      acids and flavonoids prior to high-performance liquid chromatographic analysis.
AB  - Polymeric procyanidins, phenolic carboxylic acids and flavonoids of hawthorn
      (Crataegus laevigata) were fractionated prior to HPLC analysis using column
      chromatography and solid-phase extraction (SPE). The flavonoid fraction also
      contained (-)-epicatechin. The three groups of phenolics, each with clearly
      different UV spectra, were examined by means of high-performance liquid
      chromatography-diode array detection (HPLC-DAD) analysis. The average
      repeatability of the method (RSD) was in the range of 8-13% for chlorogenic acid,
      (-)-epicatechin and hyperoside. The polymeric procyanidins of hawthorn flowers
      consisted mainly of (-)-epicatechin subunits, and their mean degree of
      polymerization (DP) was 22.2. The HPLC methods developed can be used for the
      qualitative and quantitative analysis of different phenolic compounds in hawthorn
      plant material and their extracts.

PMID- 16426621
TI  - Validated chiral high-performance liquid chromatography method for a novel anti
      methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771.
AB  - A sensitive, simple, specific, precise, accurate and rugged method for the assay
      and determination of enantiomeric purity of S-(-)-9-fluoro-6,7-dihydro-8-(4
      hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic
      acid L-arginine salt tetrahydrate (WCK 771) in bulk drug has been developed. The
      method is RP-HPLC using endcapped C-18 stationary phase and chiral mobile phase.
      Chirality to the mobile phase was imparted with addition of beta-cyclodextrin.
      The UV-vis detector was operated at 290 nm. The flow rate of mobile phase was 2
      ml/min. The method offers excellent separation of two enantiomers with resolution
      more than 2 and tailing factor less than 1.5. The method was validated for the
      assay of WCK 771 and quantification of R-(+)-enantiomer impurity in bulk drug.
      The calibration curves showed excellent linearity over the concentration range of
      0.05-0.15 mg/ml for WCK 771 and 0.5-7.5 microg/ml for R-(+)-enantiomer. The
      precision (RSD) of the assay was 0.23%. The limit of detection and limit of
      quantitation of the method for WCK 771 were 0.015 and 0.06 microg/ml,
      respectively. The limit of detection and limit of quantitation for R-(+)
      enantiomer were 0.025 and 0.09 microg/ml, respectively. The average recovery of
      the R-(+)-enantiomer was 100.5%. Same method was applied for the assay and
      determination of enantiomeric purity of WCK 771 in the intravenous formulation.

PMID- 16426622
TI  - Continuous chromatographic separation of a baclofen precursor (N-Boc-4-[p-chloro
      phenyl]-2-pyrrolidone) in a simulated moving bed using a polysaccharide carbamate
      as chiral stationary phase.
AB  - Liquid chromatography is known as one of the most flexible, efficient and cost
      effective methods to resolve racemic mixture in order to attend the growing
      demand of the pharmaceutical industry for pure enantiomeric compounds. Cellulose
      tris(3,5-dimethylphenylcarbamate) is frequently used as a stationary phase for
      enantiomeric separations because of its attractive properties, including high
      enantioselectivity, high loading capacity and good mechanical stability. In this
      study, we investigated the usefulness of cellulose tris(3,5
      dimethylphenylcarbamate) as the stationary phase and of ethanol and hexane
      mixtures as the mobile phases for the chromatographic separation of potential
      pharmaceutical intermediates. Using adsorption equilibrium data, we determined
      the optimal operational conditions for the separation of the N-Boc-4-[p-chloro
      phenyl]-2-pyrrolidone enantiomers - a baclofen precursor - in a semi-preparative
      scale simulated moving bed unit. This unit was used to obtain high purity
      enantiomers on a scale of 1g/day. The outlet streams were analyzed by an on-line
      system that consisted of a UV-vis spectrophotometric unit, a polarimeter, and
      HPLC. Enantiomeric purities of up to 97% were obtained for the raffinate stream
      and up to 90% for the extract stream.

PMID- 16426623
TI  - Determination of acrylamide and acrylic acid by isocratic liquid chromatography
      with pulsed electrochemical detection.
AB  - The electrochemical behaviour of the polycrystalline platinum electrode towards
      the oxidation/reduction of short-chain unsaturated aliphatic molecules such as
      acrylamide and acrylic acid was investigated in acidic solutions. Analytes were
      separated by reverse phase liquid chromatographic and quantified using a pulsed
      amperometric detection. A new two-step waveform, is introduced for detection of
      acrylamide and acrylic acid. Detection limits (LOD) of 20 nM (1. 4 microg/kg) and
      45 nM (3.2 microg/kg) were determined in water solutions containing acrylamide
      and acrylic acid, respectively. Compared to the classical three-step waveform,
      the proposed two-step waveform shows favourable analytical performance in terms
      of LOD, linear range, precision and improved long-term reproducibility. The
      proposed analytical method combined with clean-up procedure accomplished by
      Carrez clearing reagent and subsequent extraction with a strong cation exchanger
      cartridges (SPE), was successfully used for the quantification of low
      concentrations of acrylamide in foodstuffs such as coffee and potato fries.

PMID- 16426624
TI  - Multilinear gradient elution optimisation in reversed-phase liquid chromatography
      using genetic algorithms.
AB  - The treatment presented in a recent paper [P. Nikitas, A. Pappa-Louisi, J.
      Chromatogr. A, 1068 (2005) 279] is extended to multilinear gradients, i.e.
      continuous gradients consisting of a certain number of linear portions. Thus, the
      experimental lnk versus phi curve, where k is the retention factor of a sample
      solute under isocratic conditions and phi is the volume fraction of the organic
      modifier in the water-organic mobile phase, is subdivided into a finite number of
      linear portions resulting in simple analytical expressions for the solute
      gradient retention time. These expressions of the retention time are directly
      used in an optimisation technique based on genetic algorithms. This technique
      involves first the determination of the theoretical dependence of k upon phi by
      means of gradient measurements, which in turn is used by the genetic algorithm
      for the prediction of the best gradient profile. The validity of the analytical
      expressions and the effectiveness of the optimisation technique were tested using
      fifteen underivatized amino acids and related compounds with mobile phases
      modified by acetonitrile. It was found that the adopted methodology exhibits
      significant advantages and it can lead to high quality predictions of the
      gradient retention times and optimisation results.

PMID- 16426625
TI  - Sensitivity enhancement of liquid chromatographic-direct chemiluminescence
      detection by on-line post-column solvent mediated pre-oxidative
      chemiluminescence.
AB  - The compatibility of liquid chromatography solvents with oxidizing reagents
      frequently employed in direct chemiluminescence reactions is examined in this
      study. Various oxidizing reagents were examined for their response in hydro
      organic and micellar mobile phases in both isocratic and gradient elution modes.
      Mild oxidants like hydrogen peroxide, periodate, cerium and hypochlorite were
      found to be completely compatible with common reversed phase HPLC solvents posing
      as no threat to the detection procedure. On the other hand, stronger oxidants
      like acidic permanganate were found to oxidize organic solvents towards the
      production of an intense light signal. Although several analytical applications
      can emerge from this finding, the conjunction of this system with reversed phase
      HPLC is impractical owing to a significant baseline increase which deteriorates
      the sensitivity of the analysis. A convenient solution to this problem is
      proposed based on the regulated on-line post-column pre-oxidation of the organic
      solvent (SPOC) with mild oxidants that have no influence on the final signal. The
      analytical utility of this new approach in the determination of organic compounds
      after chromatographic separation is demonstrated.

PMID- 16426626
TI  - Isolation and identification of radical scavengers in olive tree (Olea europaea)
      wood.
AB  - Several extracts of Olea europaea wood (Picual olive cultivar) were obtained with
      solvents of different polarity and their antioxidant activities determined. The
      active compounds were detected in fractions of an ethyl acetate extract using
      HPLC with on-line radical scavenging detection. After applying different
      separation techniques, hydroxytyrosol, tyrosol, cycloolivil, 7-deoxyloganic acid,
      oleuropein and ligustroside were isolated and characterized. Hydroxytyrosol
      showed a higher activity than the natural antioxidant rosmarinic acid in
      scavenging the DPPH model radical. Cycloolivil and oleuropein showed stronger
      activities than the synthetic antioxidant BHT against the same radical.
      Ligustroside, tyrosol and 7-deoxyloganic acid showed little activity. The latter
      compound has not been previously identified in the genus Olea.

PMID- 16426628
TI  - Double gradient ion chromatography using short monolithic columns modified with a
      long chained zwitterionic carboxybetaine surfactant.
AB  - The rapid separation of inorganic anions on short monolithic columns permanently
      coated with a long chained zwitterionic carboxybetaine-type surfactant is shown.
      The surfactant, N-dodecyl-N,N-(dimethylammonio)undecanoate (DDMAU), was used to
      coat 2.5, 5.0 and 10 cm long reversed-phase silica monoliths, resulting in a
      permanent zwitterionic exchange surface when used with aqueous based eluents. The
      unique structure of the surfactant results in a charge double layer structure on
      the surface of the stationary phase, with strong internal anionic and weak
      external cationic exchange groups. The dissociation of the weak external
      carboxylic acid group acts to shield the inner anionic exchange site, resulting
      in substantial effective capacity changes with eluent pH. Utilising this effect
      with the application of an eluent pH gradient, simultaneously combined with
      eluent flow-rate gradients, very rapid simultaneous separations of both weakly
      retained anions and strongly retained polarisable anions was possible, with up to
      10-fold decreases in overall run times. Coating stability and retention times
      under isocratic and isofluentic eluent conditions were shown to be reproducible
      over >450 repeat injections, with peak efficiency values averaging 29,000 N/m for
      the 2.5 cm column and 42,000 N/m for the 10 cm monolithic column, again under
      isocratic elution conditions.

PMID- 16426629
TI  - Simple and sensitive liquid chromatographic method with fluorimetric detection
      for the analysis of gabapentin in human plasma.
AB  - A simple and sensitive liquid chromatographic method is described for the
      quantitative analysis of gabapentin in human plasma. Gabapentin (GBP) is an
      anticonvulsant and widely used in the treatment of epilepsy. No peculiar
      chromophore is available on gabapentin moiety for direct analysis by absorption
      spectrophotometry. In human plasma after deproteinisation with acetonitrile,
      gabapentin was derivatized with a fluorescent reagent, (2-naphthoxy)acetyl
      chloride (NAC) in borate buffer (pH 10.0). The resulting naphthoxy derivative of
      gabapentin was separated on a phenyl-hexyl column with a mobile phase consisting
      of a mixture of sodium acetate buffer (100 mM; pH 5.0)-methanol (32:68, v/v) used
      in isocratic mode. Using fluorimetric detection (excitation at 225 nm and
      emission at 360 nm), a low detection limit of about 0.04 microM (S/N = 3, 10
      microl injected) was reached. The relative standard deviations (RSD) of the
      method for intra- and inter- day analyses (n = 5) are between 2.7 and 4.0%,
      respectively. The method was successfully applied to the analysis of gabapentin
      in plasma from dosed patients for therapeutic drug monitoring.

PMID- 16426630
TI  - Measurement of cation binding to immobilized vanillin by isothermal calorimetry.
AB  - Isothermal calorimetry was used to determine enthalpy changes for interaction of
      divalent cobalt, nickel, copper, and zinc chlorides with silica gel
      functionalized with vanillin, Sil-Van. The thermal effect, Q(int), and the
      corresponding amount of cation that interacts, n(int), were obtained in the same
      experiment. Langmuir expressions for adsorption isotherms were applied to
      determine the maximum adsorption capacity to form a monolayer, N(mon), and the
      energy of interaction for a saturated monolayer per gram of Sil-Van, Q(mon). From
      knowledge of N(mon) and Q(mon), the molar enthalpy of interaction for formation
      of a monolayer of anchored cations per gram of Sil-Van, Delta(mon)H(m), was
      determined. Interactions between the Lewis-acidic cations and the donor atom
      attached to silica are reflected by Delta(mon)Hm values in the order Ni2+ > Cu2+
      > Zn2+ congruent with Co2+.

PMID- 16426631
TI  - Characterization of silica-coated tobacco mosaic virus.
AB  - The deposition of silica on the surface of tobacco mosaic virus (TMV) is achieved
      at a higher pH (>7) as a means to enhance its usefulness as a template for the
      synthesis of nanostructures. Electron energy loss spectroscopy definitively shows
      the presence of a silica shell on the surface of the TMV while small angle X-ray
      scattering differentiates successfully between silica-coated TMV and silica
      particles in the presence of uncoated TMV. Importantly, coating reactions done in
      a 50% w/v methanol/water solution produce smaller silica nanostructures during
      the condensation of the hydrolysis intermediates, possibly aiding in obtaining
      uniform coating. Furthermore, TMV-templated silica coatings are found to enhance
      the stability of the virus particle in methanol at conditions that would
      ordinarily disrupt the assembled particle. Combined these findings demonstrate
      that TMV can function as an efficient template for the controlled deposition of
      silica at neutral pH.

PMID- 16426632
TI  - Sea urchin arylsulfatase insulator exerts its anti-silencing effect without
      interacting with the nuclear matrix.
AB  - Chromatin insulators have been shown to stabilize transgene expression. Although
      insulators have been suggested to regulate the subcellular localization of
      chromosomes, it is still unclear whether this property is important for their
      anti-silencing activity. To investigate the underlying mechanisms governing the
      anti-silencing function of insulators, we studied the association of sea urchin
      arylsulfatase insulator (ArsI) with the nuclear matrix, which is a key component
      of the subnuclear localization of the genome. ArsI did not potentiate the nuclear
      matrix association with the transgene, even though it showed strong anti
      silencing activity. This observation was in clear contrast to the results of the
      experiment using a human interferon-beta scaffold attachment region, in which the
      anti-silencing effect coincided with the enhanced matrix association. Chromatin
      immunoprecipitation analyses suggested that the absence of the matrix binding by
      ArsI was due to a lack of its binding to CCCTC-binding factor (CTCF), a protein
      known to be associated with matrix binding by chicken beta-globin insulator.
      Furthermore, ArsI maintained the nucleosome occupancy within the transgene at a
      constant level during long-term culture, although ArsI itself was not a
      nucleosome-excluding sequence. Taken together, these results suggest that this
      insulator exerts its anti-silencing activity by counteracting silencing
      associated factors to maintain local chromatin environment, rather than by
      remodeling the subnuclear localization of the transgene locus.

PMID- 16426633
TI  - Structural mimicry of CD4 by a cross-reactive HIV-1 neutralizing antibody with
      CDR-H2 and H3 containing unique motifs.
AB  - Human immunodeficiency virus (HIV) entry into cells is initiated by the binding
      of its envelope glycoprotein (Env) gp120 to receptor CD4. Antibodies that bind to
      epitopes overlapping the CD4-binding site (CD4bs) on gp120 can prevent HIV entry
      by competing with cell-associated CD4; their ability to outcompete CD4 is a major
      determinant of their neutralizing potency and is proportional to their avidity.
      The breadth of neutralization and the likelihood of the emergence of antibody
      resistant virus are critically dependent on the structure of their epitopes.
      Because CD4bs is highly conserved, it is reasonable to hypothesize that
      antibodies closely mimicking CD4 could exhibit relatively broad cross-reactivity
      and a high probability of preventing the emergence of resistant viruses.
      Previously, in a search for antibodies that mimic CD4 or the co-receptor, we
      identified and characterized a broadly cross-reactive HIV-neutralizing CD4bs
      human monoclonal antibody (hmAb), m18. Here, we describe the crystal structure of
      Fab m18 at 2.03 A resolution, which reveals unique conformations of heavy chain
      complementarity-determining regions (CDRs) 2 and 3 (H2 and H3). H2 is highly
      bulged and lacks cross-linking interstrand hydrogen bonds observed in all four
      canonical structures. H3 is 17.5 A long and rigid, forming an extended beta-sheet
      decorated with an alpha-turn motif bearing a phenylalanine-isoleucine fork at the
      apex. It shows striking similarity to the Ig CDR2-like C'C'' region of the CD4
      first domain D1 that dominates the binding of CD4 to gp120. Docking simulations
      suggest significant similarity between the m18 epitope and the CD4bs on gp120.
      Fab m18 does not enhance binding of CD4-induced (CD4i) antibodies, nor does it
      induce CD4-independent fusion mediated by the HIV Env. Thus, vaccine immunogens
      based on the m18 epitope structure are unlikely to elicit antibodies that could
      enhance infection. The structure can also serve as a basis for the design of
      novel, highly efficient inhibitors of HIV entry.

PMID- 16426634
TI  - Structural insights into the cryptic DNA-dependent ATPase activity of UvrB.
AB  - The UvrABC pathway is a ubiquitously occurring mechanism targeted towards the
      repair of bulky base damage. Key to this process is UvrB, a DNA-dependent limited
      helicase that acts as a lesion recognition element whilst part of a tracking
      complex involving UvrA, and as a DNA-binding platform required for the
      presentation of damage to UvrC for subsequent processing. We have been able to
      determine the structure of a ternary complex involving UvrB* (a C-terminal
      truncation of full-length UvrB), a polythymine trinucleotide and ADP. This
      structure has highlighted the roles of key conserved residues in DNA binding
      distinct from those of the beta-hairpin, where most of the attention in previous
      studies has been focussed. We are also the first to report the structural basis
      underlying conformational re-modelling of the beta-hairpin that is absolutely
      required for DNA binding and how this event results in an ATPase primed for
      catalysis. Our data provide the first insights at the molecular level into the
      transformation of UvrB into an active helicase.

PMID- 16426635
TI  - Kinetics of an individual transmembrane helix during bacteriorhodopsin folding.
AB  - The kinetics of an individual helix of bacteriorhodopsin have been monitored
      during folding of the protein into lipid bilayer vesicles. A fluorescence probe
      was introduced at individual sites throughout helix D of bacteriorhodopsin and
      the changes in the fluorescence of the label were time-resolved. Partially
      denatured, labelled bacteriorhodopsin in SDS was folded directly into
      phosphatidylcholine lipid vesicles. Stopped-flow mixing of the reactants allowed
      the folding kinetics to be monitored with millisecond time resolution by time
      resolving changes in the label fluorescence, intrinsic protein fluorescence as
      well as in the absorption of the retinal chromophore. Monitoring specific
      positions on helix D showed that two kinetic phases were altered compared to
      those determined by monitoring the average protein behaviour. These two phases,
      of 6.7 s(-1) and 0.33 s(-1), were previously assigned to formation of a key
      apoprotein intermediate during bacteriorhodopsin folding. The faster 6.7s(-1)
      phase was missing when time-resolving fluorescence changes of labels attached to
      the middle of helix D. The amplitude of the 0.33 s(-1) phase increased along the
      helix, as single labels were attached in turn from the cytoplasmic to the
      extracellular side. An interpretation of these results is that the 6.7 s(-1)
      phase involves partitioning of helix D within the lipid headgroups of the bilayer
      vesicle, while the 0.33 s(-1) phase could reflect transmembrane insertion of this
      helix. In addition, a single site on helix G was monitored during folding. The
      results indicate that, unlike helix D, the insertion of helix G cannot be
      differentiated from the average protein behaviour. The data show that, while
      folding of bacteriorhodopsin from SDS into lipids is a co-operative process, it
      is nevertheless possible to obtain information on specific regions of a membrane
      protein during folding in vitro.

PMID- 16426636
TI  - Single-molecule FRET study of denaturant induced unfolding of RNase H.
AB  - Single-molecule fluorescence (Forster) resonance energy transfer (FRET)
      experiments were performed on surface-immobilized RNase H molecules as a function
      of the concentration of the chemical denaturant guanidinium chloride (GdmCl). For
      comparison, we measured ensemble FRET on RNase H solutions. The single-molecule
      approach allowed us to study FRET distributions of the subpopulation of unfolded
      molecules without interference from the folded population. The unfolded ensemble
      experienced a continuous shift of the FRET efficiency distribution with
      increasing concentration of GdmCl, indicating a heterogeneous population of
      expanding, unfolded polypeptide chains. We have analyzed the behavior of the
      unfolded state quantitatively with a model in which the unfolded state is
      described by a continuum of substates, with the free energy of each substate
      linearly coupled to its m-value, the proportionality coefficient between free
      energy and denaturant activity. By fitting this model to the data, we have
      derived energetic and structural parameters that describe the unfolded state
      ensemble. Specifically, we have found that the average size of the unfolded state
      increases from 23-38 A between 0 and 6 M denaturant. Excellent agreement was
      achieved between the fitted model and our FRET measurements, and with previously
      published nuclear magnetic resonance and small-angle X-ray scattering data.

PMID- 16426637
TI  - Electron cryomicroscopic visualization of PomA/B stator units of the sodium
      driven flagellar motor in liposomes.
AB  - A motor protein complex of the bacterial flagellum, PomA/B from Vibrio
      alginolyticus, was reconstituted into liposomes and visualized by electron
      cryomicroscopy. PomA/B is a sodium channel, composed of two membrane proteins,
      PomA and PomB, and converts ion flux to the rotation of the flagellar motor.
      Escherichia coli and Salmonella have a homolog called MotA/B, which utilizes
      proton instead of sodium ion. PomB and MotB have a peptidoglycan-binding motif in
      their C-terminal region, and therefore PomA/B and MotA/B are regarded as the
      stator. Energy filtering electron cryomicroscopy enhanced the image contrast of
      the proteins reconstituted into liposomes and showed that two extramembrane
      domains with clearly different sizes stick out of the lipid bilayers on opposite
      sides. Image analysis combined with gold labeling and deletion of the
      peptidoglycan-binding motif revealed that the longer one, approximately 70 A
      long, is likely to correspond to the periplasmic domain, and the other, about
      half size, to the cytoplasmic domain.

PMID- 16426638
TI  - Comparative genomics and protein domain graph analyses link ubiquitination and
      RNA metabolism.
AB  - The human gene parkin, known to cause familial Parkinson disease, as well as
      several other genes, likely involved in other neurodegenerative diseases or in
      cancer, encode proteins of the RBR family of ubiquitin ligases. Here, we describe
      the structural diversity of the RBR family in order to infer their functional
      roles. Of particular interest is a relationship detected between RBR-mediated
      ubiquitination and RNA metabolism: a few RBR proteins contain RNA binding domains
      and DEAH-box RNA helicase domains. Global protein domain graph analyses
      demonstrate that this connection is not RBR-specific, but instead many other
      proteins contain both ubiquitination and RNA-related domains. These proteins are
      present in animals, plants and fungi, suggesting that the link between these two
      cellular processes is ancient. Our results show that global bioinformatic
      approaches, involving comparative genomics and domain network analyses, may
      unearth novel functional relationships involving well-known and thoroughly
      studied groups of proteins.

PMID- 16426639
TI  - Plasma nitric oxide and leptin values in patients with olanzapine-induced weight
      gain.
AB  - We previously investigated leptin levels in antipsychotic-induced weight gain and
      found that atypical antipsychotic, especially clozapine and olanzapine-induced
      weight gain is related to increased levels of leptin. It has been suggested that
      nitric oxide (NO) is a potential regulator of leptin-induced lipolysis. To
      explore the pathophysiology of weight gain during atypical antipsychotic
      treatment, we planned to investigate olanzapine's influence on leptin and NO
      levels and weight gain. The study comprised 21 patients with schizophrenia who
      were enrolled in olanzapine monotherapy, and 21 healthy controls. The fasting
      plasma NO and leptin levels were measured in both patients and controls at
      baseline. The patients were also evaluated at sixth week according to the
      Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight,
      serum leptin and NO levels. At baseline, the mean leptin level in the olanzapine
      group was not different compared to that in controls after BMI or age adjustment.
      A significant increase in leptin levels by means of olanzapine use was seen
      (P<0.01). Higher plasma NO levels were observed in patients with schizophrenia
      compared with the control group at baseline (P<0.01). At the evaluation of week
      6, a significant decrease in the mean plasma NO level was found in the olanzapine
      group (P<0.05). The changes in total PANSS scores were correlated with change in
      leptin levels (r=0.58, P<0.05), and with the change in weight (r=0.54, P<0.05).
      In addition, there was a severe significant negative correlation between the
      changes in leptin levels and NO levels (r=0.73, P<0.01). The results confirmed
      that leptin and NO might be associated with olanzapine-induced weight gain.

PMID- 16426640
TI  - Inhibition of intestinal glucose uptake by aporphines and secoaporphines.
AB  - The effects of aporphines and secoaporphines on glucose uptake by isolated
      intestinal brush-border membrane vesicles (BBMV) or basolateral membrane vesicles
      (BLMV) and glucose absorption during in situ intestinal perfusion were studied.
      Of the tested compounds, N-allylsecoboldine was the most potent glucose uptake
      inhibitor, with IC50 values of 159 microM and 121 microM, respectively, for
      uptake by BBMV and BLMV. While thaliporphine competitively inhibited glucose
      uptake by both membrane preparations, inhibition by N-allylsecoboldine was
      competitive using BBMV and noncompetitive using BLMV. In addition, N
      allylsecoboldine significantly reduced both glucose absorption during in situ
      intestinal perfusion and blood glucose levels in the oral glucose tolerance test.
      The results demonstrate that levels of both aporphines and secoaporphines
      achievable by oral administration have an inhibitory effect on intestinal glucose
      uptake and suggest that the hypoglycemic effects of these compounds merit
      attention.

PMID- 16426641
TI  - Interdependency of the oxidizability of lipoproteins and peroxidase activity with
      base excess, HCO3, pH and magnesium in human venous and capillary blood.
AB  - As continuous production of free radicals and reactive oxygen species is a normal
      metabolic process, increased metabolism during exercise/workload should increase
      free radical generation and oxidative stress. Oxidative stress intensity should
      then depend on the intensity of metabolic stress effects. Intensity of stress is
      usually reflected in norepinephrine (NE) levels, which correlate linearly and
      significantly with changes in blood gases, blood buffer systems, blood
      electrolytes, blood glucose and lactate [Porta, S., Leitner, G., Heidinger, D.,
      Lang, T., Weiss, U., Smolle, K.H., Hasiba, K., 1997. Magnesium wahrend der
      Alpinausbildung bringt um 30% bessere Energieverwertung. Magnesium-Bulletin
      19(2), 59-61]. Those parameters were used in an open study design to screen 64
      subjects for metabolic stress effects along with their antioxidative capacity
      using both venous and capillary blood. To compare venous and capillary blood, we
      took venous blood samples from 12 healthy volunteers and capillary blood from 52
      other healthy subjects. To show whether free radical changes indeed go along with
      metabolic stress effects, we tried to quantify relations between metabolic stress
      effects and oxidative stress by linear correlations. In conclusion, both venous
      and capillary blood are suitable for determining at least those parameters of the
      oxidative state that we used. All significant correlations of peroxidase activity
      and oxidation lag time (OLT) with pH, bicarbonate (HCO3), base excess (BE) and
      magnesium (Mg) indicate that free radical production increases with metabolism.
      Those relationships could help to evaluate the oxidative state more precisely.

PMID- 16426642
TI  - Age-related changes in oxytocin-, arginine vasopressin- and nitric oxide synthase
      expressing neurons in the supraoptic nucleus of the rat.
AB  - Many histochemical investigations indicated that the oxytocin (OXY), the arginine
      vasopressin (AVP) and the nitric oxide synthase (NOS) have been synthesized in
      the supraoptic nucleus (SON) neurons. The objective of this study was to examine
      the age-related expression of the OXY, the AVP and the NOS in the SON of the
      young adult (2-month-old) and the aged (24-month-old) rats. The histochemistry
      for reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d;
      marker for the NOS) and the double labeling histochemistry for the OXY/NADPH-d or
      the AVP/NADPH-d were employed, and the quantitative analysis was performed with a
      computer-assisted image processing system. In comparison of the young adult and
      the aged group, the cell number, the cell size and the reactive density of the
      NOS-expressing neurons showed a significant increase along with age, and these
      evidences suggested the age-related increase of the nitric oxide (NO) production.
      The age-related significant increase was not detected in the number of the
      OXY/NOS-expressing neurons in the dorsal part, but was detected in the number of
      the AVP/NOS-expressing neurons in the ventral part. Based on our histochemical
      findings and reports demonstrated by other authors, we attempted to discuss the
      physiological role of NOS for the secretion of posterior pituitary hormones along
      with age.

PMID- 16426643
TI  - Gene expression of transforming growth factor-beta receptors types I and II in
      rat endometrium during the estrous cycle and early pregnancy.
AB  - Roles of transforming growth factor-beta (TGF-beta) receptor types I (TbetaRI)
      and II (TbetaRII) during the estrous cycle and implantation of rodents are
      currently unclear. In the present study, the spatial and temporal expressions of
      TbetaRI and TbetaRII in rat endometrium during the estrous cycle, pre-, and peri
      implantation were examined using in situ hybridization and semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR). With in situ
      hybridization, TbetaRI and TbetaRII were expressed at weak levels in rat
      endometrium during the estrous cycle. During pre-implantation, both receptors
      were expressed in the luminal epithelium and glandular epithelium on Days 0.5 and
      1.5 of pregnancy, but were down-regulated on Days 2.5 and 3.5. During peri
      implantation, both TGF-beta receptors were localized in the luminal epithelium
      and subepithelial stroma to facilitate attachment reaction and trophoblast
      invasion. They were highly expressed on Day 4.5, whereas were down-regulated on
      Days 5.5 and 6.5. Semi-quantitative RT-PCR analysis confirmed the data obtained
      by in situ hybridization. These results suggest that during pre-implantation,
      both TGF-beta receptors are functional in the proliferation of endometrial
      epithelial cells. During peri-implantation, both TGF-beta receptors play
      important roles during the onset of the uterine receptivity and the attachment
      reaction. TGF-beta signaling is down-regulated when trophoblast invasion begins.

PMID- 16426644
TI  - What is the future fate of estuaries given nutrient over-enrichment, freshwater
      diversion and low flows?
AB  - Freshwater inflow is central to the definition of estuaries and if we lose
      control of the quantity of freshwater flow or discharge (including seasonal
      timing) to estuaries, then freshwater water quality has the potential to become a
      moot issue in estuarine ecosystems (Definition of estuaries: estuaries (aestus =
      tide) are physico-chemically, geomorphically, and biotically diverse ecosystems.
      Although numerous definitions of estuaries exist, we prefer the following: an
      estuary is a partially enclosed coastal water body in which freshwater runoff,
      often seasonally and episodically pulsed, dilutes salty ocean water and the
      biotic structure is influenced by dynamic tidal action and associated salinity
      gradients and reef building organisms and wetlands influence development and
      evolution of ecological structure and function (see for expanded definition)).

PMID- 16426645
TI  - Marine monitoring: Its shortcomings and mismatch with the EU Water Framework
      Directive's objectives.
AB  - The main goal of the EU Water Framework Directive (WFD) is to achieve good
      ecological status across European surface waters by 2015 and as such, it offers
      the opportunity and thus the challenge to improve the protection of our coastal
      systems. It is the main example for Europe's increasing desire to conserve
      aquatic ecosystems. Ironically, since c. 1975 the increasing adoption of EU
      directives has been accompanied by a decreasing interest of, for example, the
      Dutch government to assess the quality of its coastal and marine ecosystems. The
      surveillance and monitoring started in NL in 1971 has declined since the 1980s
      resulting in a 35% reduction of sampling stations. Given this and interruptions
      the remaining data series is considered to be insufficient for purposes other
      than trend analysis and compliance. The Dutch marine managers have apparently
      chosen a minimal (cost-effective) approach despite the WFD implicitly requiring
      the incorporation of the system's 'ecological complexity' in indices used to
      evaluate the ecological status of highly variable systems such as transitional
      and coastal waters. These indices should include both the community structure and
      system functioning and to make this really cost-effective a new monitoring
      strategy is required with a tailor-made programme. Since the adoption of the WFD
      in 2000 and the launching of the European Marine Strategy in 2002 (and the
      recently proposed Marine Framework Directive) we suggest reviewing national
      monitoring programmes in order to integrate water quality monitoring and
      biological monitoring and change from 'station oriented monitoring' to 'basin or
      system oriented monitoring' in combination with specific 'cause-effect' studies
      for highly dynamic coastal systems. Progress will be made if the collected
      information is integrated and aggregated in valuable tools such as structure- and
      functioning-oriented computer simulation models and Decision Support Systems. The
      development of ecological indices integrating community structure and system
      functioning, such as in Ecological Network Analysis, are proposed to meet a cost
      effective approach at the national level and full assessment of the ecosystem
      status at the EU level. The WFD offers the opportunity to re-consider and re
      invest in environmental research and monitoring. Using examples from the
      Netherlands and, to a lesser extent, the United Kingdom, the present paper
      therefore reviews marine monitoring and marine environmental research in
      combination and in the light of such major policy initiatives such as the WFD.

PMID- 16426646
TI  - Inspection time in non-demented older adults with mild cognitive impairment.
AB  - The aim of this study was to examine inspection time (IT) performance in older
      adults with mild cognitive impairment (MCI), who are at higher risk of developing
      further cognitive decline or dementia. IT is described as an index of speed of
      informational intake. IT correlates with measures of fluid intelligence and is
      possibly a marker for the integrity of the cholinergic system of the brain. IT
      may therefore be useful in aiding the diagnosis of early-stage progressive
      cognitive impairment. The current study compares IT in 28 people with MCI to 28
      age, gender and education-matched controls. The computer-based, visual IT task
      required participants to discriminate between two visual stimuli that were
      presented for brief periods. Participants' IT performance was compared to their
      performance on cognitive and memory tasks. Group comparison showed that
      participants with MCI performed significantly worse on IT than controls and was
      not affected by years of education. In combination with other clinical,
      neuropsychological and biological tests, IT may be a useful assessment tool for
      improving the identification of older adults at risk for clinically relevant
      cognitive decline.

PMID- 16426647
TI  - Beccaridiol, an unusual 28-nortriterpenoid from the leaves of Diplectria
      beccariana.
AB  - A C29-triterpene, beccaridiol (1), a dihydrochalcone natural product, 2',4'
      dihydroxy-3-(4-methoxyphenyl)-propiophenone (2), as well as three known
      compounds, 4'-hydroxy-1',2'-dihydro-beta-ionone, 4'-O-methyldavidigenin (3), and
      ursolic acid, have been isolated from an EtOAc-soluble extract of the leaves of
      Diplectria beccariana. Beccaridiol (1) was characterized as an ursane-type 28
      nortriterpene possessing an unusual aromatic E-ring by spectroscopic data
      interpretation. The relative configuration of this unusual isolate was
      established by analyzing the observed NOESY NMR correlations, and the absolute
      stereochemistry of 1 was then determined based on the circular dichroism (CD)
      spectrum of its 2,3-di-p-bromobenzoate (1b) derivative. All isolates were
      evaluated for their potential cancer chemopreventive properties utilizing a cell
      culture assay to determine quinone reductase induction.

PMID- 16426648
TI  - Hydroquinone diglycoside acyl esters from the stems of Glycosmis pentaphylla.
AB  - Four hydroquinone diglycoside acyl esters, glypentosides A-C (1-3) and
      seguinoside F (4), were isolated from the stems of Glycosmis pentaphylla.
      Glypentosides A-B (1-2) were identified as compounds and designated as
      methoxyquinol 4-O-[(5-O-trans-p-coumaroyl)-beta-d-apiofuranosyl-(1-->2)-beta-d
      glucopyranoside] (1) and 4-demethylantiarol 4-O-[(3-methoxy-4-hydroxy-benzoyl)
      beta-d-apiofuranosyl-(1-->2)-beta-d-glucopyranoside] (2). Glypentoside C (3) is a
      hydroquinone diglycoside acyl ester with a neolignan moiety in the acyl unit.
      Their structures were elucidated by the combination of one- and two-dimensional
      NMR analysis, mass spectrometry and chemical evidences.

PMID- 16426649
TI  - Hydroxylation of the sesterterpene leucosceptrine by the fungus Rhizopus
      stolonifer.
AB  - The microbial transformation of leucosceptrine (1), the first member of class
      leucosesterterpenes, by Rhizopus stolonifer afforded two metabolites, 1alpha
      hydroxyleucosceptrine (2), and 8alpha-hydroxyleucosceptrine (3).

PMID- 16426650
TI  - Targeted metabolite profiling provides a functional link among eucalypt taxonomy,
      physiology and evolution.
AB  - Adaptation to aridity is considered a major factor in the evolution of the genus
      Eucalyptus. For the first time, targeted metabolite profiling has uncovered a
      quantitative yet discrete phytochemical link with eucalypt taxonomy. The
      distribution of cyclitols among Eucalyptus species, and a range of other
      Australian tree genera, support their proposed functions in plant tissues and
      provide putative links with the acclimation of trees to arid environments.

PMID- 16426651
TI  - PCR and PCR-RFLP of the 5S-rRNA-NTS region and salvinorin A analyses for the
      rapid and unequivocal determination of Salvia divinorum.
AB  - Salvia divinorum Epling & Jativa-M. is a perennial herb belonging to the
      Lamiaceae family; its active ingredient, the neoclerodane diterpene salvinorin A,
      is a psychotropic molecule that produces hallucinations. A comparative evaluation
      of S. divinorum fresh and dried leaves, S. officinalis fresh leaves, and dried
      powdered leaves claimed to be S. divinorum was done. HPLC-MS data confirmed the
      presence of salvinorin A in both S. divinorun leaf extracts and the powdered
      leaves, whereas no salvinorin A was found in S. officinalis. The non-transcribed
      spacer (NTS) in the 5S-rRNA gene of all leaf samples and the dried powdered
      leaves was amplified by PCR using a pair of primers located at the 3' and 5' ends
      of the coding sequence of 5S-rRNA gene. The resulting PCR products (about 500bp
      for S. divinorum and 300bp for S. officinalis) were gel purified, subcloned into
      pGEM-T Easy vector and sequenced. By aligning the isolated nucleotide sequences,
      great diversities were found in the spacer region of the two species. Specific S.
      divinorum primers were designed on the sequence of the 5S-rRNA gene spacer
      region. In addition, a PCR-restriction fragment length polymorphism (PCR-RFLP)
      method was applied using NdeI and TaqI restriction enzymes. An NdeI site, absent
      in S. officinalis, was found in S. divinorum NTS region at 428-433bp. For TaqI,
      multiple sites (161-164, 170-173, and 217-220bp) were found in S. officinalis,
      whereas a unique site was found in S. divinorum (235-238bp). The results of this
      work show that the combined use of analytical chemical (HPLC-MS) and molecular
      (DNA fingerprinting) methods lead to the precise and unequivocal identification
      of S. divinorum.

PMID- 16426652
TI  - Tropinone reductases, enzymes at the branch point of tropane alkaloid metabolism.
AB  - Two stereospecific oxidoreductases constitute a branch point in tropane alkaloid
      metabolism. Products of tropane metabolism are the alkaloids hyoscyamine,
      scopolamine, cocaine, and polyhydroxylated nortropane alkaloids, the
      calystegines. Both tropinone reductases reduce the precursor tropinone to yield
      either tropine or pseudotropine. In Solanaceae, tropine is incorporated into
      hyoscyamine and scopolamine; pseudotropine is the first specific metabolite on
      the way to the calystegines. Isolation, cloning and heterologous expression of
      both tropinone reductases enabled kinetic characterisation, protein
      crystallisation, and structure elucidation. Stereospecificity of reduction is
      achieved by binding tropinone in the respective enzyme active centre in opposite
      orientation. Immunolocalisation of both enzyme proteins in cultured roots
      revealed a tissue-specific protein accumulation. Metabolite flux through both
      arms of the tropane alkaloid pathway appears to be regulated by the activity of
      both enzymes and by their access to the precursor tropinone. Both tropinone
      reductases are NADPH-dependent short-chain dehydrogenases with amino acid
      sequence similarity of more than 50% suggesting their descent from a common
      ancestor. Putative tropinone reductase sequences annotated in plant genomes other
      that Solanaceae await functional characterisation.

PMID- 16426653
TI  - Cultural niche construction in a metapopulation.
AB  - Cultural niche construction is the process by which certain evolving cultural
      traits form a cultural niche that affects the evolution of other genetic and
      cultural traits [Laland, K., et al., 2001. Cultural niche construction and human
      evolution. J. Evol. Biol. 14, 22-33; Ihara, Y., Feldman, M., 2004. Cultural niche
      construction and the evolution of small family size. Theor. Popul. Biol. 65, 105
      111]. In this study we focus on cultural niche construction in a metapopulation
      (a population of populations), where the frequency of one cultural trait (e.g.
      the level of education) determines the transmission rate of a second trait (e.g.
      the adoption of fertility reduction preferences) within and between populations.
      We formulate the Metapopulation Cultural Niche Construction (MPCNC) model by
      defining the cultural niche induced by the first trait as the construction of a
      social interaction network on which the second trait may percolate. Analysis of
      the model reveals dynamics that are markedly different from those observed in a
      single population, allowing, for example, different (or even opposing) dynamics
      in each population. In particular, this model can account for the puzzling
      phenomenon reported in previous studies [Bongaarts, J., Watkins, S., 1996. Social
      interactions and contemporary fertility transitions. Popul. Dev. Rev. 22 (4), 639
      682] that the onset of the demographic transition in different countries occurred
      at ever lower levels of development.

PMID- 16426654
TI  - Exact coalescent for the Wright-Fisher model.
AB  - The Kingman coalescent, which has become the foundation for a wide range of
      theoretical as well as empirical studies, was derived as an approximation of the
      Wright-Fisher (WF) model. The approximation heavily relies on the assumption that
      population size is large and sample size is much smaller than the population
      size. Whether the sample size is too large compared to the population size is
      rarely questioned in practice when applying statistical methods based on the
      Kingman coalescent. Since WF model is the most widely used population genetics
      model for reproduction, it is desirable to develop a coalescent framework for the
      WF model, which can be used whenever there are concerns about the accuracy of the
      Kingman coalescent as an approximation. This paper described the exact coalescent
      theory for the WF model and develops a simulation algorithm, which is then used,
      together with an analytical approach, to study the properties of the exact
      coalescent as well as its differences to the Kingman coalescent. We show that the
      Kingman coalescent differs from the exact coalescent by: (1) shorter waiting time
      between successive coalescent events; (2) different probability of observing a
      topological relationship among sequences in a sample; and (3) slightly smaller
      tree length in the genealogy of a large sample. On the other hand, there is
      little difference in the age of the most recent common ancestor (MRCA) of the
      sample. The exact coalescent makes up the longer waiting time between successive
      coalescent events by having multiple coalescence at the same time. The most
      significant difference among various summary statistics of a coalescent examined
      is the sum of lengths of external branches, which can be more than 10% larger for
      exact coalescent than that for the Kingman coalescent. As a whole, the Kingman
      coalescent is a remarkably accurate approximation to the exact coalescent for
      sample and population sizes falling considerably outside the region that was
      originally anticipated.

PMID- 16426655
TI  - Revisiting matrix games: the concept of neighborhood invader strategies.
AB  - We extend the concept of neighborhood invader strategy (NIS) to finite
      dimensional matrix games and compare this concept to the evolutionarily stable
      strategy (ESS) concept. We show that these two concepts are not equivalent in
      general. Just as ESS's may not be unique, NIS's may also not be unique. However,
      if there is an ESS and a NIS then these strategies must be the same. We show that
      an ESNIS (an ESS and NIS) for any matrix game is unique and that a mixed ESS with
      full support is a NIS. Thus a mixed ESS with full support is not invadable by any
      pure or mixed strategy and it can invade any pure or mixed strategy. An ESS which
      is an ESNIS, therefore, has better chance of being established evolutionarily
      through dynamic selection.

PMID- 16426656
TI  - Immunolocalization and characterization of beta-keratins in growing epidermis of
      chelonians.
AB  - Beta-keratins constitute most of the corneous material of carapace and plastron
      of turtles. The production of beta-keratin in the epidermis of a turtle and
      tortoise (criptodirians) and of a species of pleurodiran turtle was studied after
      injection of tritiated proline during the growth of carapace, plastron and claws.
      Growth mainly occurs near hinge regions along the margins of scutes and along
      most of the claws (growing regions). Proline incorporation occurs mainly in the
      growing centers, and is more specifically associated with beta-keratin synthesis.
      Proline-labeled bands of protein at 12-14 kDa and 25-27 kDa, and 37 kDa, in the
      molecular weight range of beta-keratins, were isolated from the soft epidermis of
      turtles 3 h after injection of the labeled amino acid. After extraction of
      epidermal proteins, an antibody directed against a chicken beta-keratin was used
      for immunoblotting. Bands of beta-keratin at 15-17 kDa, 22-24 kDa, and 36-38 kDa
      appear in all species. Beta-keratin is present in the growing and compact stratum
      corneum of the hard (shell) and soft (limbs, neck and tail) epidermis. This was
      confirmed using a specific antibody against a turtle beta-keratin band of 15-16
      kDa. The latter antibody recognized epidermal protein bands in the range of 15-16
      kDa and 29-33 kDa, and labels beta-keratin filaments. This result indicates that
      different forms of beta-keratins are produced from low molecular weight
      precursors or that larger aggregate form during protein preparation. The present
      study shows that beta-keratin is abundant in the scaled epidermis of tortoise but
      also in the soft epidermis of pleurodiran and cryptodiran turtles, indicating
      that this form of hard keratin is constitutively expressed in the epidermis of
      chelonians.

PMID- 16426657
TI  - Applying fluorescence based technology to the recovery and isolation of
      Cryptosporidium and Giardia from industrial wastewater streams.
AB  - As increasing water shortages continue, water re-use is posing new challenges
      with treated wastewater becoming a significant source of non-potable water. Rapid
      detection strategies that target waterborne pathogens of concern to industry are
      gaining importance in the assessment of water quality. This study reports on the
      ability to recover spiked Cryptosporidium and Giardia from a variety of
      industrial wastewater streams of varied water quality. Incorporation of an
      internal quality control used commonly in finished water-enabled quantitative
      assessments of pathogen loads and we describe successful analysis of pre- and
      part-treated wastewater samples from four industrial sites. The method used
      combined calcium carbonate flocculation followed by flow cytometry and
      epifluorescence microscopy. Our focus will now aim at characterising the ambient
      parasites isolated from industrial wastewater with the objective of developing a
      suite of highly specific platform detection technologies targeted to industrial
      needs.

PMID- 16426658
TI  - Uptake of chloride ion from aqueous solution by calcined layered double
      hydroxides: equilibrium and kinetic studies.
AB  - Layered double hydroxides (LDH) calcined within a certain temperature range
      (denoted as CLDH) have been shown to recover their original layered structure in
      the presence of appropriate anions. In the light of this so-called "memory
      effect", uptake of chloride ion from aqueous solution by calcined MgAl-CO3 LDH
      was investigated in batch mode. The equilibrium isotherm showed that the uptake
      of chloride ion by CLDH was consistent with the Langmuir and Freundlich equations
      and that the Langmuir model gave a better fit to the experimental data than the
      Freundlich model. The maximum uptake capacity of CLDH for chloride ion was 149.5
      mg/g, close to the stoichiometric uptake (168 mg/g). The influence of varying pH
      of solution, initial chloride concentration, adsorbent quantity, and temperature
      on the kinetics of chloride removal has also been explored. Four kinetic models
      were used to fit the experimental data, and it was found that the pseudo-second
      order kinetics model could be used to describe the uptake process satisfactorily.
      The calculated value of Ea was found to be 56.8 kJ/mol, which suggests that the
      process of uptake of chloride ion is controlled by the rate of reaction of
      chloride ion with the CLDH rather than diffusion. A mechanism for removal of
      chloride ion has been confirmed by X-ray diffraction, FT-IR spectroscopy and TG
      MS measurements.

PMID- 16426659
TI  - A test of porous pavement effectiveness on clay soils during natural storm
      events.
AB  - Porous pavements allow precipitation to infiltrate through the pavement to the
      soil, reducing the volume of stormwater runoff produced at a site. However,
      porous pavements are not widely used on fine-grained soils due to concerns about
      their performance. Our objective was to investigate the efficacy of porous
      pavements in controlling stormwater runoff on clay soils. We compared the
      performance of an asphalt parking lot and a porous pavement parking lot of grass
      pavers in Athens, Georgia, USA, over relatively small and low-intensity rain
      events. The porous lot produced 93% less runoff than the asphalt lot. The total
      volume of runoff at the porous lot was significantly less than the asphalt lot (t
      = 2.96, p = 0.009). Turbidity was significantly greater at the asphalt lot (t =
      6.18, p < 0.001) whereas conductivity was significantly higher at the porous lot
      (t = 2.31, p = 0.03). Metal and nutrient concentrations were below detection
      limits at both lots during seven of nine small storm events. During events in
      which we could detect pollutants, calcium, zinc, silica, and total phosphorus
      concentrations were higher at the asphalt lot whereas total nitrogen
      concentrations were greater at the porous lot. Our results suggest porous
      pavements are a viable option for reducing stormwater runoff and some pollutants
      from small storms or the first flush from large storms on clay soils.

PMID- 16426660
TI  - Decreasing effluent loads through bleaching modification.
AB  - Almost all of the kraft pulp bleach plants worldwide are now practicing elemental
      chlorine-free (ECF) process to comply with environmental regulations in different
      countries. Usually, these conventional ECF bleaching sequences contain one or two
      alkaline extraction stages of which the first one is often the principal source
      of color and chemical oxygen demand (COD) in the resulting effluent. However, the
      results of this study showed that the ECF sequences which did not include any
      alkaline extraction stage and contained solely chlorine dioxide decreased both
      the color and COD loads of the effluent. On the other hand, the ECF sequences
      containing both chlorine dioxide and hydrogen peroxide but excluding the alkaline
      extraction stage could lower only the color but not the COD load. It is suggested
      that the total kappa factor (the ratio of the total active chlorine to the kappa
      number) affected the COD load and that the content of hexeneuronic acid groups
      influenced the color of the bleach effluent. Compared to the reference pulp, the
      viscosity of the pulp from the exclusively chlorine-dioxide-based ECF sequence
      without the alkaline extraction stage was lower but the tear index and sheet
      density at a given tensile index were similar.

PMID- 16426661
TI  - Effects of temperature and water content on degradation of isoproturon in three
      soil profiles.
AB  - The phenylurea herbicide isoproturon, 3-(4-isopropylphenyl)-1,1-dimethylurea
      (IPU), is widely used to control pre- and post-emergence of grass and broad
      leaved weeds in cereal crops. Its degradation in soils is a key process for
      assessing its leaching risk to groundwater resources. The degradation properties
      of various samples from surface and subsurface soil (down to 1m depth) of a
      heterogeneous agricultural field were studied using (14)C-IPU. Laboratory
      incubations were carried out at 22 and 10 degrees C and at water contents 90% and
      50% of the estimated water holding capacity (eWHC) corresponding to water
      potentials between -56 kPa and -660 MPa. Degradation was found to be more
      sensitive to water content variations than to temperature variations in the
      ranges that we used. For surface layers, at 10 and 22 degrees C, the degradation
      half-life increased by a factor 10 and 15, respectively, when water content
      decreased from 90% to 50% eWHC. Under optimal degradation conditions (i.e. 22
      degrees C and 90% eWHC), 3-(4-isopropylphenyl)-1-methylurea (MDIPU) was the main
      metabolite in surface samples. At subsurface depths, IPU half-lives were larger
      than 100 d, IPU was the main compound after 92 d of incubation and the main
      metabolite was an unidentified polar metabolite. These results suggest a
      metabolic pathway involving hydroxylations for subsurface materials. IPU
      degradation was largely affected by water availability in both surface and
      subsurface horizons. Clay content seemed to play a major role in degradation
      processes in subsurface soil by determining through sorption IPU availability in
      soil solution and/or by limiting water availability for microorganisms.

PMID- 16426662
TI  - A new bacterial strain mediating As oxidation in the Fe-rich biofilm naturally
      growing in a groundwater Fe treatment pilot unit.
AB  - A bacterial strain B2 that oxidizes arsenite into arsenate was isolated from the
      biofilm growing in a biological groundwater treatment process used for Fe
      removal. This strain is phylogenetically and morphologically different from the
      genus Leptothrix commonly encountered in biological iron oxidation processes. T
      RFLP fingerprint of the biofilm revealed that this isolated strain B2 corresponds
      to the major population of the bacterial community in the biofilm. Therefore, it
      is probably one of the major contributors to arsenic removal in the treatment
      process.

PMID- 16426663
TI  - Sources of hydrocarbons in sediments of the Bay of Fort de France (Martinique).
AB  - Sedimentary hydrocarbons have been studied quantitatively and qualitatively in 16
      stations of the Bay of Fort de France (Martinique). Hydrocarbon levels ranged
      from 54 to 1045 mg kg(-1) sed. dry weight. Origin of hydrocarbons are multiple:
      biogenic (terrestrial inputs), pyrolytic (residues of natural or anthropogenic
      combustions), diagenetic and anthropogenic (petroleum contamination). Generally
      high levels of hydrocarbons are not associated to a petroleum contamination. The
      main source of hydrocarbons in the mangrove coastal zones of the Bay of Fort de
      France seems to be the early diagenetic degradation products of 3
      oxytriterpenoids. Excepted two stations, petroleum contamination is very low or
      absent.

PMID- 16426664
TI  - Biosorption of lead ion by chemically-modified biomass of marine brown algae
      Laminaria japonica.
AB  - In this paper, marine brown algae Laminaria japonica was chemically-modified by
      crosslinking with epichlorohydrin (EC(1), EC(2)), or oxidizing by potassium
      permanganate (PC), or only washed by distilled water (DW). They were used for
      equilibrium sorption uptake studies with lead. As can be seen from the
      experimental results that biosorption equilibriums were rapidly established in
      about 2h. The lead adsorption was strictly pH dependent, and maximum removal of
      lead on biosorbents were observed at pH 5.3. The effects solid/liquid ratio on
      lead biosorption was also investigated. The maximum lead uptakes were 1.67 mmol
      g(-1), 1.62 mmol g(-1), 1.54 mmol g(-1) and 1.21 mmol g(-1), respectively for
      EC(1), EC(2), PC and DW. The order of maximum lead uptakes for different
      pretreated and raw alga was EC(1)>EC(2)>PC>DW. A comparison of different isotherm
      models revealed that the combination of Langmuir and Freundlich (L-F) isotherm
      model fitted the experimental data best.

PMID- 16426665
TI  - Analysis of the level of comprehension of chemical hazard labels: a case for
      Zambia.
AB  - We have surveyed the impact of chemical hazard label elements on four target
      sectors, i.e. the agricultural, industrial, transport and the consumer (the
      general public) sectors, in order to assess the type of reactions the respondents
      perceive to a given chemical label element such as symbol, hazard phrase, color,
      and hazard signal word. The survey revealed that the level of education, gender
      and/or age did not influence the respondents' perception of the extent of hazard
      but rather familiarity or frequency of use of the chemicals and acquaintance with
      chemical label elements was significant in the assessment of the extent of
      perceived hazard posed by a given chemical. Symbols such as the St Andrews Cross-
      though common--is virtually not understood by more than 80% of the respondents in
      all the sectors. We noted that respondents appreciate symbols they can relate to,
      which are flame-like, ghost-like and exert immediate impacts to respondents.
      Color codes have found use in the agriculture sector because of their ease to be
      recalled especially by the majority of illiterate farm workers. The survey
      revealed that red in agricultural circles is well associated with high toxicity
      while other colors such as yellow and blue can not clearly be associated with
      hazard. The word "toxic" is not used in the industry and transport sectors where
      the most hazard signal word is "danger". The Globally Harmonized System (GHS)
      classification adopted "danger" and "warning" for use as signal words. The survey
      revealed that effective chemical hazard symbols must not be too abstract to the
      client but should contain features that are known or easily comprehended.

PMID- 16426666
TI  - Once atrial fibrillation, always oral anticoagulation?

PMID- 16426667
TI  - A new plastic collection tube made of polyethylene terephtalate is suitable for
      monitoring traditional anticoagulant therapy (oral anticoagulant, unfractionated
      heparin, and low molecular weight heparin).
AB  - To improve the safety of blood collection, plastic tubes have been developed but
      various interactions with the coagulation system and/or antithrombotic drugs were
      reported with the first generation of such tubes. The aim of this multicentre
      study was to compare hemostasis test results measured in evacuated plastic tubes
      made of polyethylene terephtalate (VenoSafe, Terumo Europe) and in siliconized
      glass tubes containing the same citrate concentration (0.129 M). In addition, the
      impact of aging of the plastic tube was investigated by collecting blood samples
      in tubes at 8 months and at 1 month before expiry. Blood was drawn in 3 centres
      from untreated patients (n=269), patients on oral anticoagulant treatment (OAT,
      n=221), and patients treated with either unfractionated heparin (UFH, n=73) or a
      low molecular weight derivative (LMWH, n=48). Prothrombin time (PT) or INR,
      activated partial thromboplastin time (APTT) and anti-FXa activity were locally
      performed, when applicable. In untreated patients and in patients on OAT, PT and
      APTT values were found statistically shorter (p<0.05) when evaluated in plastic
      tubes than in glass tubes, except when PT was evaluated using a human
      thromboplastin. Surprisingly, significantly longer APTT and higher anti-FXa
      activities were obtained when blood from patients on UFH was drawn in plastic
      than in glass tubes. However, none of the differences had any clinical relevance
      (Bland-Altman analysis). In patients on anticoagulant treatment, there was no
      effect of aging of the plastic tubes. These results suggest that the plastic tube
      VenoSafe is suitable for coagulation testing both in untreated subjects and more
      interestingly in patients on traditional anticoagulant therapy during the whole
      shelf life indicated by the manufacturer.

PMID- 16426668
TI  - Total pelvic exenteration: the Albert Einstein College of Medicine/Montefiore
      Medical Center Experience (1987 to 2003).
AB  - OBJECTIVE: To review the trends, modifications and results of 103 consecutive
      total pelvic exenterations (TPE) performed at the Montefiore Medical Center and
      Albert Einstein College of Medicine from 1987 to 2003. METHODS: All patients who
      underwent TPE from January 1987 to December 2003 were included. The medical
      record, complications, follow-up, clinical status and demographic information
      were entered in a database. The procedure performed, the method of urinary
      diversion, colonic diversion, pelvic floor support and vaginal reconstruction
      were documented. Surviving patients were surveyed regarding their satisfaction
      with the urinary diversion, the vaginal reconstruction and their sexual function
      since the surgery. RESULTS: 103 pts were identified. Indications for TPE were
      recurrent cancers of the cervix (95), endometrium (2), colon and rectum (5),
      vulva (1). Overall 5-year survival was 47%. 5-year survival for pts with
      recurrent cervix cancer was 48%. Six pts (6%) recurred >5 years after the TPE. 14
      pts (14%) had ureteral anastomotic leaks (no difference between ileal conduit
      9/65 (14%) versus 5/38 (13%) continent conduit (P = 0.92). 34 pts (89%) with
      continent conduits were "continent." 14 pts (17%) had wound complications. 4 pts
      (4%) had parastomal hernias. 5/11 (46%) pts who had a low rectal reanastomosis
      developed recurrence in the pelvis. 21/39 (54%) of pts with continent conduits
      would choose an ileal conduit if they had the option again. Long-term renal
      function was similar in pts with ileal and continent conduits. Mesh of any type
      for pelvic floor reconstruction is associated with infection and bowel/urinary
      fistulas. VRAM flaps for neovagina fill the pelvic dead space, reduce the risk of
      fistulas and 20/36 pts (55%) are sexually active. CONCLUSIONS: Our overall 5-year
      survival is encouraging, and modifications in surgical technique have improved
      the reconstructive phase. Low rectal anastomoses at TPE adversely affects
      survival. Many of our pts with continent urinary diversions would not choose this
      method again. Mesh of any type is associated with sepsis and bowel/urinary
      fistulas. VRAM for neovagina reduces fistula rate and are functional in >55% of
      pts. TPE remains a potentially curative option for these pts.

PMID- 16426669
TI  - Pharmacokinetics of repeated doses of intravenous cocaine across the menstrual
      cycle in rhesus monkeys.
AB  - Numerous studies in rodents suggest that there are sex differences in response to
      cocaine that are related to fluctuations in the ovarian hormones of females.
      Given that female rhesus monkeys have menstrual cycles that are remarkably
      similar to those of humans, they provide an ideal laboratory animal model for
      assessing the effects of cocaine across the menstrual cycle. The present study
      assessed the effects of 4 injections of intravenous (i.v.) cocaine (0.00, 0.25 or
      0.50 mg/kg), spaced 15 min apart, in 4 female rhesus monkeys. Each monkey was
      tested with each dose during 4 phases of the menstrual cycle: menses,
      midfollicular, periovulatory and midluteal. Estradiol and progesterone levels
      were measured each session before cocaine administration to verify phase of the
      menstrual cycle. Cocaine and cocaine metabolite levels were measured 5 min after
      each cocaine dose and 5, 15, 30, 45, 60 and 120 min after the last cocaine dose.
      Similarly, levels of luteinizing hormone (LH) and prolactin levels were measured
      before, 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Cocaine and
      metabolite levels increased as a function of dose, but there were minimal
      differences across the menstrual cycle following repeated injections of cocaine.
      With a few exceptions, LH levels decreased as a function of time within the
      session, with no differences as a function of cocaine dose. Cocaine produced
      transient increases in LH levels during the luteal phase, with maximal levels
      occurring after the second cocaine injection. Lastly, cocaine substantially
      decreased prolactin levels across all menstrual cycle phases. Taken together,
      these data indicate that any behavioral differences observed either across the
      menstrual cycle or between males and females, are probably not related to
      alterations in the pharmacokinetics of cocaine across the menstrual cycle.

PMID- 16426670
TI  - Real-time ultrasound measure of the fetal eye (vitreous body) for prediction of
      parturition date in small ponies.
AB  - Ultrasonographic fetal eye measures have been used to estimate gestational age of
      the fetus in light horse mares. However, fetal eye measures have not been
      published for smaller pony breeds. This study was conducted to develop reference
      ranges for ultrasonographic measures of fetal eyes in small ponies for the
      purpose of predicting days before parturition (DBP) when breeding or ovulation
      dates are unknown. Twenty-three Shetland-type pony mares were studied across one
      (n = 10) or two (n = 13) gestations in 2004 (18 pregnancies) and 2005 (18
      pregnancies). Measurements of fetal eyes were obtained during transrectal
      ultrasound examination. Examinations were conducted once monthly in a field
      situation beginning in December (2003) or August (2004) until mares foaled (March
      through July). The length (from sclera to sclera) and width (from retina to
      cornea) of the vitreous body were measured. For the 273 examinations in which
      gestation age was greater than 2 months, eye measures were obtainable in 248
      (91%). Mixed-effects linear regression modeling was used to account for serial
      growth measures within pregnancy, repeated measurements across mares, and
      unbalanced study design. Independent variables evaluated included vitreous body
      length, vitreous body width, the ratio of length to width, parity, and mare
      height at the withers at parturition. Eye length was the best single predictor of
      days before parturition, with almost no additional predictive value of the other
      variables considered. Our resulting regression equation is: days before
      parturition=265.16-0.21*(vitreous body length in mm)(2). This study suggests that
      measure of the fetal eye is a practical on-farm procedure for estimating days
      before parturition in small ponies.

PMID- 16426671
TI  - Effects of oocyte activation and sperm preparation on the development of porcine
      embryos derived from in vitro-matured oocytes and intracytoplasmic sperm
      injection.
AB  - The objective was to determine the effects of various methods of oocyte
      activation and sperm pretreatment on development of porcine embryos derived from
      in vitro-matured oocytes and intracytoplasmic sperm injection (ICSI). The second
      polar body was extruded in the majority (>78.4%) of in vitro-matured (IVM)
      oocytes 4h after electrical pulse activation. In embryos generated by ICSI and
      sham-ICSI, a combination of an electrical pulse, with various chemical activators
      4 h later, improved (P < 0.05) blastocyst formation rate compared to activation
      only with a pulse. Treatment with 6-dimethylaminopurine (DMAP) after electrical
      activation significantly increased the oocyte activation rate. The effects of
      exposure of sperm to repeated freeze-thaw cycles (without cryoprotectant) on
      oocyte activation and the effects of sperm pre-incubated with dithiothreitol
      (DTT) or Triton X-100 on early embryo development were also examined. Blastocyst
      formation rates after ICSI did not differ between motile sperm and those rendered
      immotile by one-time freezing and thawing without cryoprotectant. However, sperm
      rendered immotile by three cycles of freezing/thawing without cryoprotectant had
      a significantly lower blastocyst formation rate. Although oocytes injected with
      sperm pre-incubated with Triton X-100 had a higher normal fertilization rate than
      those pre-incubated with DTT or one-time frozen/thawed sperm, rates of blastocyst
      formation and cell numbers were similar among the three groups. In conclusion,
      various methods of oocyte activation and sperm preparation significantly affected
      the developmental capacity of early porcine embryos derived from IVM and ICSI.

PMID- 16426672
TI  - Cytotoxicity of resin monomers on human gingival fibroblasts and HaCaT
      keratinocytes.
AB  - OBJECTIVES: The aim of this study was to evaluate and compare the biological
      effects of three resin monomers on three human gingival fibroblast (HGF) cell
      lines and immortalised human keratinocytes. METHODS: Primary HGFs and HaCaT
      keratinocytes were cultured for 24h and grown to sub-confluent monolayers. Resin
      monomers were dissolved in dimethyl sulphoxide (DMSO) and diluted with culture
      medium. Cultures were exposed to different concentrations of monomers (10(-2) to
      10mM) for 24h. Cell viability measured by Alamar Blue assay, and cell culture
      supernatant was examined for the presence of human interlukin-1beta (IL-1beta)
      using sandwich enzyme-linked immunosorbant assay (ELISA). TC50 values were
      calculated from fitted dose-response curves. RESULTS: All monomers showed toxic
      effects on the HGFs and HaCaT cells and inhibited chemical reduction of Alamar
      Blue in high concentrations. Statistical analysis of TC50 values by one-way ANOVA
      followed by Tukey's analysis showed that there is a significant difference in
      TC50 values between the cell lines (p<0.05), although the rank order of monomer
      toxicity remained the same for different cell lines. None of these monomers
      induced IL-1beta release from HGFs and HaCaT cells. SIGNIFICANCE: Dental resin
      monomers are toxic to human gingival fibroblasts and HaCaT keratinocytes.
      However, they cannot induce IL-1beta release from these cells by themselves.
      Alamar Blue assay is a sensitive method for the evaluation of cytotoxicity and it
      can detect different sensitivities of different cell lines to the resin monomers.

PMID- 16426674
TI  - Predicting identity consolidation from self-construction, eudaimonistic self
      discovery, and agentic personality.
AB  - The present study was conducted to ascertain the extent to which three
      alternative perspectives on identity development (self-construction,
      eudaimonistic self-discovery, and agentic personality) relate to various indices
      of identity consolidation drawn from Erikson, identity status, and identity
      capital. A total of 183 participants (21% males; 78% ethnic minorities) completed
      measures drawn from Eriksonian, identity status, self-construction, eudaimonistic
      self-discovery, and identity capital perspectives. Self-construction,
      eudaimonistic self-discovery, and agentic personality (as operationalized within
      the identity capital model) each showed differential patterns of relationships to
      measures of identity consolidation, suggesting that all three strategies can be
      used to develop a sense of identity.

PMID- 16426673
TI  - Bonding effectiveness of adhesive luting agents to enamel and dentin.
AB  - OBJECTIVES: The bonding effectiveness of five adhesive luting agents to enamel
      and dentin using different application procedures was determined using a micro
      tensile bond strength protocol (microTBS). METHODS: Enamel/dentin surfaces of
      human third molars were flattened using a high-speed diamond bur. Composite resin
      blocks (Paradigm, 3M ESPE) were luted using either Linkmax (LM; GC), Nexus 2 (NX;
      Kerr), Panavia F (PN; Kuraray), RelyX Unicem (UN; 3M ESPE) or Variolink II (VL;
      Ivoclar-Vivadent), strictly following manufacturers' instructions. For some
      luting agents, modified application procedures were also tested, resulting in
      four other experimental groups: Prompt L-Pop+RelyX Unicem (PLP+UN; 3M ESPE),
      Scotchbond Etchant+RelyX Unicem (SE+UN; 3M ESPE), Optibond Solo Plus
      Activator+Nexus 2 (ACT+NX; Kerr) and K-Etchant gel+Panavia-F (KE+P; Kuraray). The
      experimental groups were classified according to the adhesive approach in self
      adhesive (UN), etch-and-rinse (ACT+NX, NX, KE+P, SE+UN and VL when bonded to
      enamel) and self-etch adhesive luting agents (LM, PLP+UN, PN and VL when bonded
      to dentin). The specimens were stored for 24h in distilled water at 37 degrees C
      prior to microTBS testing. The Kruskal-Wallis test was used to determine pairwise
      statistical differences (p<0.05) in microTBS between the experimental groups.
      RESULTS: When bonded to enamel, ACT+NX (15 MPa) and UN (19.6 MPa) scored
      significantly lower than VL (49.3 MPa), LM (49.2 MPa), PN (35.4 MPa) and SE+UN
      (35.2 MPa), while PLP+UN (23.5 MPa) showed a significantly lower microTBS than VL
      (49.3 MPa) and LM (49.2 MPa). No significant differences were noticed between VL
      (49.3 MPa), LM (49.2 MPa), NX (37.9 MPa), KE+PN (38.8 MPa), PN (35.4 MPa) and
      SE+UN (35.2 MPa). Regarding the bonding effectiveness to dentin, all luting
      agents bonded equally effectively (UN: 15.9 MPa; LM: 15.4 MPa; PN: 17.5 MPa; NX:
      22.3 MPa), except VL (1.1 MPa), SE+UN (5.9 MPa) and ACT+NX (13.2 MPa). VL
      revealed an exceptionally high number of pre-testing failures, most likely due to
      a combined effect of not having cured the adhesive separately and an
      insufficiently light-cured luting agent. SIGNIFICANCE: Following a correct
      application procedure, the etch-and-rinse, self-etch and self-adhesive luting
      agents are equally effective in bonding to enamel and dentin. Several factors
      negatively influenced bond strength such as bonding RelyX Unicem to enamel
      without prior phosphoric acid etching; no separate light-curing of a light
      polymerizable adhesive prior to cementation, use of a light-polymerizing adhesive
      converted into a dual-polymerizing adhesive, and use of a dual-cure luting agent
      with a low auto-polymerizable potential.

PMID- 16426675
TI  - Relationship between shell weight and cadmium content in whole digestive gland of
      the Japanese scallop Patinopecten yessoensis (Jay).
AB  - Seasonal and age-specific variations of cadmium (Cd) concentration in the
      digestive gland were investigated in the Japanese scallop Patinopecten yessoensis
      from Peter the Great Bay, Sea of Japan, with different degrees of Cd pollution.
      The seasonal changes in Cd concentrations of the digestive gland were inversely
      proportional to the dry weight of the gland. Concentrations of Cd and total Cd
      content (mug Cd per organ) increased with age (age-specific) to the same extent
      in contaminated and uncontaminated areas. There was also a strong positive
      correlation between Cd content in the whole digestive gland and shell weight and
      it is proposed that this relationship can be used as a new criterion for
      comparative evaluation of Cd levels in scallops from different areas We
      hypothesize that Cd is uptaken into scallops in proportion to the amount of
      calcium that absorbed through ion channels, and in addition, Cd in the digestive
      gland is in immobile forms (e.g. metal-rich granules) that accumulate with age.
      Moderate environmental pollution has no effect on the relationship between Cd
      content and shell size and the observed decrease in growth performance of the
      scallops from polluted areas may be due to other factors.

PMID- 16426676
TI  - Studies on the hydrothermal modifications of new cocoyam (Xanthosoma
      sagittifolium) starch.
AB  - Native new cocoyam starch (nNCS) was subjected to annealing (aNCS) and heat
      moisture treatment at 18% moisture level (h18NCS), 21% moisture level (h21NCS),
      24% moisture level (h24NCS) and 27% moisture level (h27NCS) as hydrothermal
      treatments. Scanning electron and light microscopy revealed round and polygonal
      shapes with sizes ranging from 15 to 40 microm for native and modified starches.
      nNCS showed "A" pattern X-ray diffraction and no significant differences were
      observed in the X-ray pattern of the modified starches. Swelling power and
      solubility reduced following heat moisture treatment. At all pH studied (2-12),
      unmodified new cocoyam starch exhibited higher swelling capacity and solubility
      than the modified derivatives. Hydrothermal modifications improved water
      absorption capacity but reduced oil absorption capacity. Pasting temperature of
      native starch shifted to higher values following annealing and heat moisture
      treatment. Hot paste viscosity (Hv), viscosity after 30 min holding at 95 degrees
      C (Hv30) and cold paste viscosity (Cv) reduced after annealing and heat moisture
      treatment. The result also indicates that hydrothermal treatments reduced the
      tendency for setback. As the number of days of storage of starch paste increased
      from 1 to 10, light transmittance of all the starches reduced but marked
      reduction of light transmittance was observed in native starch. DSC studies
      revealed increase in gelatinization temperature following annealing and heat
      moisture treatment. Starch hydrothermal modifications reduced retrogradation as
      enthalpies of regelatinization reduced following modifications. The
      regelatinization peak in the second day scanning shifted to lower temperature
      than the gelatinization peak in first run heating DSC curve for all samples. The
      regelatinization peak also became larger and shifted to higher temperature range
      when the storage days increased from 2 to 7.

PMID- 16426677
TI  - Examination of the effects of poly(N-vinylpyrrolidinone) hydrogels in direct and
      indirect contact with cells.
AB  - Poly(N-vinylpyrrolidinone) (PNVP) has been used in various biomedical
      applications for many years. This study explores two PNVP hydrogels for their
      biocompatibility with skin cells and their ability to support the growth of skin
      cells in direct and indirect contact with the cells. Two crosslinked PNVP's were
      investigated, one crosslinked with ethylene glycol dimethacrylate (EGDMA) and the
      other crosslinked with diethylene glycol bisallylcarbonate (DEGBAC). The
      different crosslinkers lead to hydrogels with different mechanical and slightly
      different biological properties. While neither hydrogel proved to be a suitable
      substrate for culturing cells (based on fibroblasts and a range of other cells),
      indirect contact with both showed them to be biocompatible and even stimulatory
      to fibroblasts. The P(NVP-co-DEGBAC) hydrogel stimulated fibroblast viability
      more reliably than the P(NVP-co-EGDMA) hydrogel when in indirect contact with
      cells. This effect was shown to be independent of the presence of foetal calf
      serum in the culture media, and could not be explained by any hydrogel breakdown
      products during the course of these experiments. Rather the phenomenon was
      observed to be the result of a dynamic interaction between the hydrogels and the
      cells.

PMID- 16426678
TI  - The influence of architecture on degradation and tissue ingrowth into three
      dimensional poly(lactic-co-glycolic acid) scaffolds in vitro and in vivo.
AB  - The in vitro and in vivo degradation properties of poly(lactic-co-glycolic acid)
      (PLGA) scaffolds produced by two different technologies-thermally induced phase
      separation (TIPS), and solvent casting and particulate leaching (SCPL) were
      compared. Over 6 weeks, in vitro degradation produced changes in SCPL scaffold
      dimension, mass, internal architecture and mechanical properties. TIPS scaffolds
      produced far less changes in these parameters providing significant advantages
      over SCPL. In vivo results were based on a microsurgically created arteriovenous
      (AV) loop sandwiched between two TIPS scaffolds placed in a polycarbonate chamber
      under rat groin skin. Histologically, a predominant foreign body giant cell
      response and reduced vascularity was evident in tissue ingrowth between 2 and 8
      weeks in TIPS scaffolds. Tissue death occurred at 8 weeks in the smallest pores.
      Morphometric comparison of TIPS and SCPL scaffolds indicated slightly better
      tissue ingrowth but greater loss of scaffold structure in SCPL scaffolds.
      Although advantageous in vitro, large surface area:volume ratios and varying pore
      sizes in PLGA TIPS scaffolds mean that effective in vivo (AV loop) utilization
      will only be achieved if the foreign body response can be significantly reduced
      so as to allow successful vascularisation, and hence sustained tissue growth, in
      pores less than 300 microm.

PMID- 16426679
TI  - Evaluation of the osteogenesis and biodegradation of porous biphasic ceramic in
      the human spine.
AB  - The histological reports on porous biphasic calcium phosphate ceramic (PBC) in
      human spine are limited. The osteogenesis and biodegradation of PBC are
      insufficiently known in human. In present study, the undecalcified histological
      study was carried out on 20 samples retrieved from posterior spinal fusion in
      order to reveal the osteogenesis and biodegradation of the PBC in human spine.
      The quantitative study was performed in 14 samples with sufficient size. Newly
      formed bone was found in all the samples. More new bone was formed in those
      samples closely in contact with autogenous bone. The PBC degradation particles
      were present both in the macrophages and around the tissue. However, those
      phenomena were highly variable among the samples. New bone formation increased
      with time and decreased with age. The PBC degradation decreased with age, but it
      did not differ greatly with time. New bone formation was higher and the residual
      material was lower in the fusion group than that in non-fusion group. The PBC is
      a kind of osteoconductive material and do not transform into new bone after a
      relatively long time. The PBC should be well mixed with the autogenous bone in
      order to achieve high new bone colonization. The PBC degradation particles and
      related active phagocytotic activity have been noted.

PMID- 16426680
TI  - Comprehensive gene expression profiling following DNA vaccination of rainbow
      trout against infectious hematopoietic necrosis virus.
AB  - The DNA vaccine based on the glycoprotein gene of Infectious hematopoietic
      necrosis virus induces a non-specific anti-viral immune response and long-term
      specific immunity against IHNV. This study characterized gene expression
      responses associated with the early anti-viral response. Homozygous rainbow trout
      were injected intra-muscularly (I.M.) with vector DNA or the IHNV DNA vaccine.
      Gene expression in muscle tissue (I.M. site) was evaluated using a 16,008 feature
      salmon cDNA microarray. Eighty different genes were significantly modulated in
      the vector DNA group while 910 genes were modulated in the IHNV DNA vaccinate
      group relative to control group. Quantitative reverse-transcriptase PCR was used
      to examine expression of selected immune genes at the I.M. site and in other
      secondary tissues. In the localized response (I.M. site), the magnitudes of gene
      expression changes were much greater in the vaccinate group relative to the
      vector DNA group for the majority of genes analyzed. At secondary systemic sites
      (e.g. gill, kidney and spleen), type I IFN-related genes were up-regulated in
      only the IHNV DNA vaccinated group. The results presented here suggest that the
      IHNV DNA vaccine induces up-regulation of the type I IFN system across multiple
      tissues, which is the functional basis of early anti-viral immunity.

PMID- 16426681
TI  - Trimethyltin-induced alterations in behavior are linked to changes in PSA-NCAM
      expression.
AB  - The neurotoxic heavy metal trimethyltin (TMT) primarily damages neurons of the
      hippocampus and limbic areas of the temporal lobe, and causes a dose-dependent
      decrease in the polysialated form of the neural cell adhesion molecule (PSA-NCAM)
      in the mouse hippocampus. In the current study, we attempted to associate
      deficits in spatial learning following TMT exposure at various stages in learning
      with changes in levels of NCAM-180 and PSA-NCAM in both the hippocampus and
      frontal cortex. Mice were treated with TMT either before or after training on a
      spatial learning paradigm and examined for changes in NCAM and PSA-NCAM 12h
      later. In the first set of experiments, male BALB/c mice were injected with TMT
      (2.25 mg/kg) or saline i.p. and tested 24-168 h later using hidden and visible
      versions of the water maze, as well as light avoidance and motor activity. Mice
      in both treated and control groups which demonstrated a significant improvement
      in water maze performance also showed an elevation in hippocampal PSA-NCAM at all
      time points examined. TMT exposure impaired spatial learning and blocked learning
      induced elevations in PSA-NCAM expression 24-96 h post-treatment, but these
      deficits disappeared by 168 h post-treatment. Mice exposed to TMT during
      reconsolidation of spatial learning (after repeated water maze training)
      demonstrated a mild and transient difference in escape latency compared to saline
      exposed mice. TMT administration during this period did not result in the
      attenuation of PSA-NCAM expression observed when animals were exposed before
      training. These results confirm a specific role for PSA-NCAM in acquisition and
      consolidation of spatial memory.

PMID- 16426682
TI  - Reactive species and apoptosis of neural precursor cells after gamma-irradiation.
AB  - This study addresses the participation of radiation-induced free radicals, mainly
      nitric oxide (NO), in modulating the apoptotic response in an in vitro model of
      neural cortical precursor cells exposed to gamma-radiation. Cortical cells
      obtained from rats at 17 gestational day (GD) were irradiated with a dose of 2
      Gy. The percentage of apoptotic cells was significantly increased 4h post
      irradiation (pi). NO content showed a significant increase after 30 min pi and
      the rate of generation reached a maximum 1h pi. Luminol-dependent
      chemiluminescence (CL) was significantly higher in cells after 2h pi as compared
      to control cells and this profile was maintained up to 4 h pi. Supplementation
      with L-NAME significantly increased light emission. Administration of superoxide
      dismutase (SOD) following L-NAME addition prevented the observed changes due to L
      NAME administration. The caspase inhibitor zDEVD-fmk significantly reduced the
      radical generation. Moreover, the cellular decrease in NO content occurred
      coincidentally with the rise in oxygen radical generation and the activation of
      caspase-3. In vitro irradiation of neural precursor cells allowed us to suggest
      that an early radiation-induced generation of NO could exert a neuroprotective
      role. However, despite this NO initial protective effect and its role modulating
      the response against gamma-radiation, NO generation was not able of fully
      preventing radiation-induced apoptosis.

PMID- 16426683
TI  - CYP17- and CYP11B-dependent steroid hydroxylases as drug development targets.
AB  - Steroid hormone biosynthesis is catalyzed by the action of a series of cytochrome
      P450 enzymes as well as reductases. Defects in steroid hydroxylating P450s are
      the cause of several severe defects such as the adrenogenital syndrome (AGS),
      corticosterone methyl oxidase (CMO) I or II deficiencies, or
      pseudohermaphroditism. In contrast, overproduction of steroid hormones can be
      involved in breast or prostate cancer, in hypertension, and heart fibrosis.
      Besides inhibiting the action of the steroid hormones on the level of steroid
      hormone receptors by using antihormones, which often is connected with severe
      side effects, more recently the steroid hydroxylases themselves turned out to be
      promising new targets for drug development. Since the 3-dimensional structures of
      steroid hydroxylases are not yet available, computer models of the corresponding
      CYPs may help to develop new inhibitors of these enzymes. During the past years,
      the necessary test systems have been developed and new compounds have been
      synthesized, which displayed selective and specific inhibition of CYP17, CYP11B2,
      and CYP11B1. With some of these potential new drugs, clinical trials are under
      way. It can be expected that in the near future some of these compounds will
      contribute to our arsenal of new and selective drugs.

PMID- 16426684
TI  - Peptide ELISA for measuring antibodies to N-protein of porcine reproductive and
      respiratory syndrome virus.
AB  - Indirect and competition ELISAs with synthetic peptides were used to characterize
      the epitopes of the N-protein of porcine reproductive and respiratory syndrome
      virus (PRRSV) that are recognized by a battery of monoclonal antibodies (mAbs)
      and by antibodies from infected pigs. Four linear epitopes recognized by mAbs
      have been identified in the most hydrophilic segment of the N-protein (AA25-57).
      Similarly, at least four linear epitopes in this segment are immunogenic in PRRSV
      infected pigs, but only one corresponds to an epitope recognized by one of the
      mAbs (AA36-45). Antibody formation to these epitopes varied greatly between
      individual pigs. Most infected pigs generated antibodies that bound to both
      peptides and HerdChek plates, which are commonly used in the sero-diagnosis of
      PRRSV infections, but the time course of formation of peptide binding antibodies
      and antibodies that react with HerdChek plates differed greatly between pigs.
      This suggests that, although the peptide and HerdChek ELISAs may detect
      antibodies to some of the same epitopes, they also seem to detect antibodies to
      epitopes that are uniquely expressed by one and not the other. Some mAbs fail to
      bind to HerdChek ELISA plates and this is also the case for certain pig
      antibodies. Peptide ELISA results identified four herds in which most or all pigs
      possessed N-protein peptide binding antibodies, even though they were HerdChek
      ELISA sero-negative and exhibited no other signs of PRRSV infection. Thus PRRSV
      infections may be more widespread than presently realized involving strains that
      cause asymptomatic infections. The peptide ELISA is useful as an adjunct to the
      HerdChek ELISA or it could replace it since only two serum samples among 450
      tested were HerdChek ELISA positive but peptide ELISA negative. The peptide ELISA
      is also considerably cheaper than the HerdChek ELISA, more flexible and can
      provide information on the epitope specificity of the reacting antibodies.

PMID- 16426685
TI  - Bile fluorescence, heme oxygenase induction, and increased biliverdin excretion
      by mixtures of environmental toxicants.
AB  - The measurement of bile fluorescence has become a popular biomarker to
      demonstrate the exposure of fish to polycyclic aromatic hydrocarbons. Conflicting
      data has been published on how to normalize bile fluorescence. To investigate if
      normalization to biliverdin is a suitable method, experiments were performed to
      study the mechanisms related to biliverdin excretion in fish. In two separate
      experiments channel catfish (Ictalurus punctatus) were dosed with mixtures of
      benzo[a]pyrene with cadmium, chlorinated phenols or borneol. The results showed
      linear relationships between bile protein and biliverdin for each treatment
      group, but the slope of this relationship was significantly increased when fish
      received more chemical stress. Thus, under increasing toxicant stress, more
      biliverdin was excreted per amount of protein. To investigate if the increased
      biliverdin excretion was related to increased heme degradation, enzymatic
      activity of heme oxygenase (HO) was measured in liver homogenates of the dosed
      fish. The fish dosed with chemical mixtures had a significantly higher HO
      activity than the control fish, and in both experiments a significant correlation
      was observed between HO activity and biliverdin concentration in the bile. It is
      concluded that mixtures of environmental pollutants can induce HO activity and
      that this chemical stress leads to increased biliverdin excretion. The
      elucidation of this mechanistic pathway warrants that bile fluorescence should
      not be expressed per biliverdin absorption, and that expression per bile protein
      would be a more reliable method.

PMID- 16426686
TI  - Development of a new low cost high sensitivity system for behavioural ecotoxicity
      testing.
AB  - The amphipod Gammarus pulex has been extensively used for ecotoxicological
      studies. However, the tests used are either labourious to perform and/or require
      relatively expensive equipment. We report the development of a new low cost infra
      red actograph system that measures relative activity, and can detect the
      behavioural effects of very low concentrations of heavy metals. Trials
      demonstrated that the home built system can distinguish significantly different
      behaviour between G. pulex exposed to clean water and that contaminated with as
      low as 10 microg L(-1) copper. This highly sensitive low cost automated system
      has the potential to become an important tool for ecotoxicity testing and water
      quality monitoring.

PMID- 16426687
TI  - Cloning and characterization of a novel zinc finger protein (rZFP96) in the rat
      corpus luteum.
AB  - The corpus luteum (CL) is a temporary organ involved in the maintenance of
      pregnancy. In the course of its life-cycle, the CL undergoes two distinct and
      consecutive processes for its inevitable removal through apoptosis: functional
      and structural luteolysis. We isolated a gene encoding for a novel rat zinc
      finger protein (ZFP), named rat ZFP96 (rZFP96) from an ovarian lambda cDNA
      library. Sequence analysis revealed close sequence and structural similarity to
      mouse ZFP96 and human zinc finger protein 305 (ZNF305). Quantitative reverse
      transcription-polymerase chain reaction analysis revealed a positive correlation
      with the end of pregnancy, that is, the onset of structural luteolysis of the CL.
      Messenger RNA levels increased 3-fold (P < 0.01) between days 13 and 22 of
      pregnancy and 8-fold (P < 0.01) between day 13 of pregnancy and day 1 post
      partum. In addition, we detected rZFP96 expression in mammary, placenta, heart,
      kidney and skeletal muscle. Sequence analysis predicted that rZFP96 has a high
      probability of localizing to the nuclear compartment. The presence of both a
      perfect consensus TGEKP linker sequence between zinc fingers 2 and 3 as well as
      several similar sequences between the other zinc fingers suggests physical
      interaction with DNA. Speculatively, rZFP96 may therefore function as a
      transcription factor, switching-off pro-survival genes and/or upregulating pro
      apoptotic genes and thereby contributing to the demise of the CL.

PMID- 16426688
TI  - Atherosclerotic vascular disease may be associated with osteoporosis or
      osteopenia in postmenopausal women: a preliminary study.
AB  - The objective of this study was to determine if there is an association between
      osteoporosis or osteopenia and atherosclerotic vascular disease (AVD) (two
      conditions quite prevalent in nursing homes) in a sample of postmenopausal women.
      We conducted a retrospective chart review on 101 postmenopausal women in a
      university-affiliated nursing home to investigate if there is an association
      between osteoporosis or osteopenia and AVD. Bone mineral density (BMD) was
      measured by DEXA scan obtained from a computerized radiology database. Low BMD
      was defined as > or =1.5 standard deviations below the mean of a cohort of young
      women. AVD was diagnosed if documented coronary artery disease, cerebrovascular
      disease, or peripheral arterial disease was present. The mean age and prevalence
      of smoking, hypertension, diabetes mellitus, and hypercholesterolemia were not
      significantly different between 51 women with osteoporosis or osteopenia and 50
      women with normal BMD. AVD was present in 31 of 51 women (51%) with osteoporosis
      or osteopenia and in 19 of 50 women (38%) with a normal BMD (p<0.025).

PMID- 16426689
TI  - Household responses to public home care programs.
AB  - A choice-theoretic model of household decision-making with respect to care-giving
      time allocations and the use of publicly and privately financed home care
      services are proposed. Predictions concerning the effect of increased
      availability of publicly financed home care services on home care utilization,
      informal care giving, and health status are derived. These predictions are
      assessed through use of Canadian inter-provincial survey data on home care use
      and care giving that are matched with data on home care funding for the period
      1992-1998. Increased availability of publicly financed home care is associated
      with an increase in its utilization, a decline in informal care giving, and an
      improvement in self-reported health status.

PMID- 16426690
TI  - Examining structural breaks and growth rates in international health
      expenditures.
AB  - Over the last decade, there has been a growing interest in examining health
      expenditures. In this paper, we study the behaviour of health expenditures in the
      G3 countries (USA, the UK, and Japan) and three European countries (the UK,
      Switzerland and Spain) over the period 1960-2000 from a different perspective, in
      that we examine: (1) whether there is a common structural break in health
      expenditures across the G3 and European countries; (2) whether structural breaks
      have slowed down health expenditure growth rates in these countries or vice
      versa. Our main findings are that: (1) health expenditures share a common break
      in both bivariate and trivariate cases, and structural breaks and break intervals
      suggest that either one or a combination of events (second oil price shock, the
      1987 stock market crash and/or recessions) have contributed to the commonality of
      break in health expenditures in the G3, while the oil price shocks have been
      instrumental in the commonality of breaks for the European countries; (2) except
      for the UK, structural breaks have slowed down growth rates in health
      expenditures for the USA, Japan, Switzerland and Spain.

PMID- 16426691
TI  - Psychophysiological anticipation of positive outcomes promotes advantageous
      decision-making in normal older persons.
AB  - Previous studies have demonstrated that aging has an adverse effect on laboratory
      decision-making in some older adults, and such findings have important
      implications for real-world reasoning and judgment. Emotion, and its accompanying
      somatic responses, is thought to contribute significantly to decision-making. In
      the present study, we had two objectives: 1) to investigate decision-making in a
      new sample of elderly participants, using the Iowa Gambling Task (IGT); and 2) to
      investigate psychophysiological correlates of decision-making, focusing on
      anticipatory skin conductance responses (SCRs) that participants produce
      immediately prior to their behavioral response. We hypothesized that the previous
      behavioral findings would be replicated, and further, that the older adult
      participants with IGT impairments would show a lack of discriminatory
      anticipatory SCRs during the IGT. The results supported both predictions. First,
      a subgroup of the new elderly sample demonstrated impaired decision-making on the
      IGT, replicating our previous findings. Second, the participants with impaired
      IGT performance failed to demonstrate discriminatory anticipatory SCRs for
      advantageous versus disadvantageous choices, whereas participants with normal IGT
      performance did demonstrate such discrimination; in the latter case, however, SCR
      magnitude was higher for advantageous decisions (unlike the pattern in young
      normal adults). Our data lead to the suggestion that strong decision-making
      abilities among older adults may be a function of positive somatic markers,
      whereas poor decision-making abilities may arise from an abnormal somatic
      response generated in anticipation of a future event.

PMID- 16426692
TI  - Energetical bases of extraversion: effort, arousal, EEG, and performance.
AB  - This study investigates an extension of H.J. Eysenck's [Eysenck, H.J., 1967. The
      Biological Basis of Personality. Charles C. Thomas, Springfield, IL] arousal
      theory of extraversion, incorporating an effort system as a control system for
      different aspects of arousal. Extraverts were expected to have lower levels of
      reticocortical arousal than introverts, to invest more effort, and to have lower
      task performance in a monotonous vigilance task. In a 40-min vigilance task,
      participants had to react to the shorter of two 1 kHz tones presented binaurally
      at an event rate of 200 per 10 min. Spontaneous EEG, event-related potential, and
      performance data of 40 extremely introverted and 41 extremely extraverted
      students were available for statistical analysis. A tendency for lower arousal
      levels of extraverts (alpha 2 band), the expected higher effort investment (P300)
      and a lower performance (hits) of extraverts were found.

PMID- 16426693
TI  - Regeneration of the abdominal postganglionic sympathetic system.
AB  - The abdominal sympathetic system is unique in that its postganglionic axons do
      not directly innervate gastrointestinal smooth muscle layers but exert their
      effects through the enteric nervous system. The purpose of the present study was
      to examine the ability of neurons in abdominal sympathetic ganglia to regenerate
      after axonal injury and to determine whether reinnervation occurs after the
      removal of ganglia. Axons from the celiac ganglion and superior mesenteric
      ganglion complex (CG/SMG) of adult female BALB/c mice were crushed or the
      ganglion complex was removed. Immunohistochemistry, western blotting and in situ
      hybridization were performed to examine the changes in tyrosine hydroxylase (TH)
      and growth-associated protein 43 (GAP-43) in the duodenum and the sympathetic
      ganglia. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      and injection of the tracer dye, fluorogold were also performed. After crushing
      the nerve, TH in the duodenum disappeared and reappeared within 90 days. In the
      CG/SMG, TH decreased and increased as in the duodenum, while the expression of
      GAP-43 changed in the opposite direction. Nerve crushing caused cell death to
      limited number of neurons in the CG/SMG. The removal of CG/SMG decreased TH in
      the duodenum and stomach, but 180 days later TH-positive innervation was
      recovered. Fluorogold injection revealed that the inferior mesenteric ganglion
      reinnervated the stomach. Therefore, postganglionic sympathetic nerves in the
      abdomen are able to regenerate and reinnervation occurs even after the removal of
      sympathetic ganglia.

PMID- 16426694
TI  - W/O microemulsions for ocular delivery: evaluation of ocular irritation and
      precorneal retention.
AB  - Water-in-oil microemulsions (w/o ME) capable of undergoing a phase-transition to
      lamellar liquid crystals (LC) or bicontinuous ME upon aqueous dilution were
      formulated using Crodamol EO, Crill 1 and Crillet 4, an alkanol or alkanediol as
      cosurfactant and water. The hypothesis that phase-transition of ME to LC may be
      induced by tears and serve to prolong precorneal retention was tested. The ocular
      irritation potential of components and formulations was assessed using a modified
      hen's egg chorioallantoic membrane test (HET-CAM) and the preocular retention of
      selected formulations was investigated in rabbit eye using gamma scintigraphy.
      Results showed that Crill 1, Crillet 4 and Crodamol EO were non-irritant.
      However, all other cosurfactants investigated were irritant and their irritation
      was dependent on their carbon chain length. A w/o ME formulated without
      cosurfactant showed a protective effect when a strong irritant (0.1 M NaOH) was
      used as the aqueous phase. Precorneal clearance studies revealed that the
      retention of colloidal and coarse dispersed systems was significantly greater
      than an aqueous solution with no significant difference between ME systems
      (containing 5% and 10% water) as well as o/w emulsion containing 85% water.
      Conversely, a LC system formulated without cosurfactant displayed a significantly
      greater retention compared to other formulations.

PMID- 16426695
TI  - The value of the screening test for gestational diabetes in pregnant Iranian
      women.
AB  - Screening for gestational diabetes mellitus (GDM) with a 50g glucose challenge
      has become standard practice in obstetrics. However, there are little data
      comparing the recommended cut-off points of 130 or 140mg/dl in Asian populations.
      To determine the optimal threshold for the screening test in an Iranian
      population, we examined data from 412 pregnant women who underwent both the
      screening glucose challenge and diagnostic glucose tolerance tests, between the
      24th and 28th week's gestation. Receiver operator curve characteristics suggested
      that 140mg/dl was the optimal threshold for the screening test for GDM in our
      population. Whilst a 130mg/dl cut-off point increases the sensitivity of the
      test, the cost implications may be prohibitive in developing countries.

PMID- 16426696
TI  - Geographic variation, physician characteristics, and diabetes care disparities in
      a metropolitan area, 2003-2004.
AB  - Quality improvement begins with quality measurement. Quality improvement
      continues by examining variation in patient standards of care. Diabetes is a
      complex chronic disease requiring aggressive care to improve and prolong life.
      Identifying and determining what factors explain care variation-including
      physician office location, physician characteristics, practice factors, and the
      translation of knowledge over time-is an area of important research. Determining
      physician practice characteristics' impact on these diabetes measures is an
      important step in understanding diabetes care in greater Kansas City. Aggregated
      diabetes HEDIS data from numerous private insurance plans from greater Kansas
      City, and associated practice factors from these same providers serves as a large
      and representative source of information to evaluate the impact of these factors
      on diabetes care. Using both multivariate and logistic methods, we find that the
      variation in care is largely explained by physician office location, but there is
      statistical explanatory significance for physician age on A1c testing rates.
      Also, nephropathy screening rates are positively related to whether a physician
      is a member of a group or a solo practice. The location of a practice has
      significant effects for diabetes care because physician office location
      approximates to some extent patient characteristics. This is not to say that
      physician practice factors are unimportant, rather that diabetes care is complex,
      and requires a fruitful interaction between physician and patient. Quantifying
      the interaction between an informed, activated patient and a prepared, proactive
      physician is difficult to observe and measure, and evaluating testable hypotheses
      about this interaction is correspondingly difficult.

PMID- 16426697
TI  - Amantadine triple therapy for non-responder hepatitis C patients. Clues for
      controversies (ANRS HC 03 BITRI).
AB  - BACKGROUND/AIMS: To determine whether addition of amantadine to pegylated
      interferon/ribavirin improved response rates among chronic hepatitis C patients,
      non-responders to interferon/ribavirin and study the dynamic of response.
      METHODS: In a double blind, multicenter, randomized trial, 200 non-responder
      patients received pegylated interferon 1.5 microg/kg per week and ribavirin 800
      1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks. Endpoints
      were virological responses, ALT normalization, and histological benefit overtime.
      RESULTS: Twenty percent of all patients achieved a sustained virological response
      (SVR). This rate was 8% higher in the triple therapy group (24%) compared with
      the double therapy group (16%) (P = 0.22). A better virological response rate at
      week 24 was observed in the triple regimen group (43 vs 29%; P = 0.06), which was
      lost at week 48 suggesting viral escape. The biochemical response rate was also
      significantly higher with triple therapy at week 12 (63 vs 49%; P = 0.05) and
      week 24 (64 vs 49%; P = 0.03). Fibrosis stabilized or improved in 77% of all
      patients. CONCLUSIONS: Re-treatment of interferon/ribavirin non-responder
      patients should be encouraged since a substantial proportion benefits from re
      treatment with pegylated interferon/ribavirin +/- amantadine. In triple therapy
      involving amantadine, a time wise response and an increased SVR rate in subgroups
      less prone to viral breakthrough suggest clues for existing controversies.

PMID- 16426698
TI  - Accumulation of dysfunctional effector CD8+ T cells in the liver of patients with
      chronic HCV infection.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) causes a chronic infection that can lead
      to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes
      (CTLs) could be involved in viral clearance or persistence, and therefore in
      determining the course of the disease. METHODS: Intrahepatic and peripheral blood
      CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed
      by flow-cytometry for surface markers of differentiation, IFNgamma and TNFalpha
      production, degranulation capacity and perforin content, after CD3 triggering.
      Results were compared with those obtained from 13 patients with a non-viral liver
      disease. RESULTS: Intrahepatic CD8+T cells of HCV-infected patients, despite
      their phenotype of pre-terminally and terminally differentiated effectors (CCR7
      CD45RA-/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation
      compared with those obtained from uninfected subjects. This defect correlates
      with the severity of fibrosis, is more pronounced in patients with ALT<1.5xN than
      with ALT>1.5xNU/ml, and is not evident after mitogen stimulation. CONCLUSIONS:
      The present study describes the accumulation of hypo-responsive CD8+T cells in
      the liver of patients with chronic HCV infection. Understanding the mechanisms
      underlying this impairment may be helpful in the design of innovative strategies
      for HCV treatment.

PMID- 16426699
TI  - How to assess liver fibrosis and for what purpose?

PMID- 16426700
TI  - The coming wave of HCV-related liver disease: dilemmas and challenges.

PMID- 16426701
TI  - A fast routine for fitting Cox models with time varying effects of the
      covariates.
AB  - The S-plus and R statistical packages have implemented a counting process setup
      to estimate Cox models with time varying effects of the covariates. The data set
      has to be re-arranged in a repeated measurement setting: the time is divided into
      small time intervals where a single event occurs and for each time interval, the
      covariate values and outcome in the interval for each subject still under
      observation are stacked to a large data set. This is the known (Tstart,Tstop]
      algorithm implemented in Therneau's Survival library (S-plus), which has been
      ported into an R package by Thomas Lumley. However, the expansion of a data set
      leads to a larger set, which can be hard to handle even with fast modern
      computers. We propose the use of a fast and efficient algorithm, written in R,
      which works on the original data without the use of an expansion. The
      computations are done on the original data set, with significant less memory
      resources used. This improves the computational time by orders of magnitude. The
      algorithm can also fit reduced rank Cox models with time varying effects. We
      illustrate the method on a large data set of 2433 breast cancer patients, a
      smaller study of 358 ovarian cancer patients, and compare the computational times
      on simulated data of up to 10,000 cases with SAS proc phreg and survival package
      in R. For larger data sets our algorithm was several times faster, and was able
      to handle larger data sets then SAS and R.

PMID- 16426702
TI  - Neuropeptide Y administration into the amygdala alters high fat food intake.
AB  - The orexigenic effects of neuropeptide Y (NPY) are mediated through the
      hypothalamus, while the anxiolytic effects of NPY appear to be mediated through
      the amygdala. We hypothesized that intra-amygdalar administration of NPY might
      alter food preference without changing total food intake. Neuropeptide Y was
      administered into the central nucleus of the amygdala in both satiated and
      overnight-fasted rats, and intake and preference for a high fat diet (56%)/low
      carbohydrate (20%) diet or a low fat (10%)/high carbohydrate (66%) diet were
      measured. Intra-amygdalar NPY administration in satiated rats did not change
      total caloric intake, but it did produce a dose-dependent decrease in intake of
      and preference for high fat diet relative to low fat diet over 24 h. In overnight
      fasted rats, intra-amygdalar NPY also decreased the intake and preference for a
      high fat diet relative to low fat diet over 24 h, without altering total caloric
      intake. Intra-amygdalar NPY administration did not produce conditioned taste
      aversions to a novel saccharin solution. These results suggest that amygdalar NPY
      may have a role in macronutrient selection, without altering total caloric
      intake.

PMID- 16426703
TI  - Wound repair and proliferation of bronchial epithelial cells enhanced by bombesin
      receptor subtype 3 activation.
AB  - The present study was designed to investigate the role of bombesin receptor
      subtype 3 (BRS-3) in airway wound repair. The results showed that: (1) There was
      few expression of BRS-3 mRNA in the control group. In contrast, the expression of
      BRS-3 mRNA was gradually increased in the early 2 days, and peaked on the fourth
      day, and then decreased in the ozone-stressed AHR animal. BRS-3 mRNA was
      distributed in the ciliated columnar epithelium, monolayer columnar epithelium
      cells, scattered mesenchymal cells and Type II alveolar cells; (2) The wound
      repair and proliferation of bronchial epithelial cells (BECs) were accelerated in
      a concentration-dependent manner by BRS-3 activation with P3513, which could be
      inhibited by PKA inhibitor H89. The study demostrated that activation of BRS-3
      may play an important role in wound repair of AHR.

PMID- 16426705
TI  - Increased glutamine synthetase but normal EAAT2 expression in platelets of ALS
      patients.
AB  - Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and glutamate
      excitotoxicity has been implicated in its pathogenesis. Platelets contain a
      glutamate uptake system and express components of the glutamate-glutamine cycle,
      such as the predominant glial excitatory amino acid transporter 2 (EAAT2). In
      several neurological diseases platelets have proven to be systemic markers for
      the disease. We compared properties of key components of the glutamate-glutamine
      cycle in blood platelets of ALS patients and healthy controls. Platelets were
      analyzed for (3)H-glutamate uptake in the presence or absence of thrombin and for
      EAAT2 and glutamine synthetase protein expression by Western blotting. Platelets
      of ALS patients showed a 37% increase in expression of glutamine synthetase, but
      normal expression of glutamate transporter EAAT2. Glutamate uptake in resting or
      thrombin-stimulated platelets did not differ significantly between platelets from
      ALS patients and controls. Thrombin-stimulation resulted in about a seven-fold
      increase in glutamate uptake. Our data suggest that glutamine synthetase may be a
      peripheral marker of ALS and encourage further investigation into the role of
      this enzyme in ALS.

PMID- 16426704
TI  - Ghrelin gastrokinetic action in patients with neurogenic gastroparesis.
AB  - Ghrelin has been shown to accelerate gastric emptying in animals where its effect
      appeared mediated through the vagus nerve. We aimed to verify the gastrokinetic
      capacity of ghrelin in human. Patients with gastroparesis attributed to a neural
      dysregulation by diabetes (n = 5) or surgical vagotomy (n = 1) were evaluated.
      The emptying of a test meal (420 kcal) was determined by the C13 octanoic acid
      breath test. Saline or synthetic ghrelin 1-4 microg/kg were given in 1 min bolus
      at the end of the meal. T-lag and T-1/2 were shorter during ghrelin than during
      saline administration [33 +/- 5 min versus 65 +/- 14 min (p < 0.01) and 119 +/- 6
      min versus 173 +/- 38 min (p < 0.001)]. Ghrelin injection therefore accelerated
      gastric emptying of a meal in humans even in presence of a deficient gastric
      innervation.

PMID- 16426706
TI  - Suppressors, receptors and effects of cytokines on the aging mouse biological
      clock.
AB  - During aging, levels of inflammatory cytokines increase and circadian rhythms are
      frequently altered. We here investigated neurobiological correlates of
      neuroinflammation and its age-related variation in the hypothalamic
      suprachiasmatic nucleus (SCN), the master circadian pacemaker. Day/night
      variations of transcripts encoding cytokine receptors and suppressors of cytokine
      signaling (SOCS) were correlated in groups of mice of different ages with Fos
      induction elicited by intracerebroventricular injections of tumor necrosis factor
      alpha and interferon-gamma. Cytokine-elicited Fos induction was high at early
      night, when SOCS1 and SOCS3 levels were low. Such Fos induction was significantly
      reduced in the older SCN at early night, and paralleled by reduced expression of
      interferon-gamma receptor transcripts as compared to the younger SCN. In
      addition, Fos induction at early night exhibited marked sub-regional differences
      in the SCN between the age groups. The study shows that SOCS1 and SOCS3 are
      expressed in the biological clock with a day/night variation that may regulate
      SCN responsiveness to cytokine exposure, and indicates that effects of pro
      inflammatory cytokines on the SCN are markedly altered during senescence.

PMID- 16426707
TI  - [Fulminant polyneuropathy and streptococcal bacteraemia].

PMID- 16426709
TI  - [Pseudomembranous diphtheria caused by Corynebacterium ulcerans].
AB  - INTRODUCTION: Pseudomembranous angina are classically caused by Corynebacterium
      diphtheriae. More rarely, it caused by Corynebacterium ulcerans, sometimes
      carrying the diphteric exotoxine. EXEGERIS: We report a new autochton case of
      pseudomembranous pharyngitis caused by C. ulcerans, carrying the diphteric
      exotoxine, transmitted by a dog, complicated of velopharyngitis and hypopharyngee
      paralysis, then of diphtheric polyneuritis. CONCLUSION: Although exceptional,
      diphteria must always be evoked in front of a pseudomembranous angina. The
      insolation of C. ulcerans must make seek diphteric toxin and its complications.

PMID- 16426708
TI  - [Cryptococcal meningitis disclosed by visual loss in HIV negative patient with
      ventriculo-atrial shunting].
AB  - INTRODUCTION: HIV infection is the main cause of cryptococcal neuromeningitis but
      other diseases may be associated with this infection. CASE REPORT: We report a
      case of cryptococcal neuromeningitis in a patient with sarcoidosis and
      ventriculoatrial shunting. The patient was successfully treated by effective
      therapy without device withdrawal. CONCLUSION: The relationship between
      cryptococcosis and sarcoidosis has been already described and may be not
      fortuitous. However it remains a very rare complication of sarcoidosis. Because
      of its potential severity (mortality rate of 40%), the diagnosis of
      cryptococcosis should be evoked as a differential diagnosis of neuro-sarcoidosis.

PMID- 16426710
TI  - Effects of polyphenolic antioxidants on exercise-induced oxidative stress.
AB  - Polyphenols are of increasing interest to consumers and food manufacturers for
      several reasons. Commonly referred to as antioxidants (they are the most abundant
      antioxidants in our diets), they may prevent various oxidative stress-related
      diseases, such as cancer, cardiovascular disease, inflammation and others.
      Physical activity is known to induce oxidative stress in individuals after
      intensive exercise. In this study, the effect of the flavonoid contents (which
      are the most abundant polyphenols) was investigated, as the only antioxidant in a
      replacement drink designed for sportsmen on various oxidative stress biomarkers
      after two identical trials of sub-maximal aerobic exercise, in a group of 30
      sportsmen. In one of the trials, the cyclists consumed the antioxidant supplement
      (with 2.3g polyphenols/trial), and in another they consumed a placebo. Blood
      samples were collected both at rest and after exercise immediately and 45 minutes
      (min) later, for measurements of plasmatic indices of oxidative stress: lipid
      oxidation (TBARS), total antioxidant status (TAS); protein oxidation (carbonyl
      groups, CO) and the lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes
      for each trial. All values were adjusted for changes in plasma volume. No changes
      were detected in plasma TAS and LDH after exercise or after the polyphenolic
      supplement. CK and TBARS increased after exercise in both tests. However, in
      response to strenuous exercise, the polyphenol-supplemented test showed a smaller
      increase in plasma TBARS and CK than the placebo test. CO increased by 12% in
      response to the placebo test, whereas it decreased by 23% in the polyphenol
      supplement test. This may indicate that the antioxidant supplement offered
      protection against exercise-induced oxidative stress.

PMID- 16426713
TI  - Re: the LPM Titanium semi-constrained proximal interphalangeal joint replacement.

PMID- 16426712
TI  - A pseudotype vesicular stomatitis virus containing Hantaan virus envelope
      glycoproteins G1 and G2 as an alternative to hantavirus vaccine in mice.
AB  - We examined whether a vesicular stomatitis virus (VSV) pseudotype bearing the
      hantavirus envelope glycoproteins (GPs) G1 and G2 (VSVdeltaG*HTN) could be used
      as a safe and effective alternative to native hantavirus. Mice were immunized
      with purified particles of VSVdeltaG*HTN. After the second immunization, all mice
      produced anti-GP antibody as detected in ELISA and a neutralization test. After
      the third immunization, the mice were challenged with Hantaan virus. Neither anti
      NP antibody production nor Hantaan virus-specific CD8 T-cell reactions were
      detected in these mice. The present study demonstrated the potential of using a
      pseudotype VSV system as a tool for developing a hantavirus vaccine.

PMID- 16426711
TI  - DNA immunization of dairy cows with the clumping factor A of Staphylococcus
      aureus.
AB  - Blocking the primary stages of Staphylococcus aureus infection, specifically the
      bacterial adhesion to cell and the colonization of the mucosal surface, may be
      the most effective strategy for preventing infections. Clumping factor A (ClfA)
      is considered to be one of the most important adhesions factors of S. aureus to
      host cells. The present study describes the immune response of dairy cattle to a
      DNA vaccine against ClfA and evaluates the ability of specific genetic adjuvants,
      targeting sequences (granulocyte macrophage colony-stimulating factor and
      cytotoxic T lymphocyte antigen-4) and transporter molecules (chitosan and
      copolymer) to modify the immune response of cows. The results show that
      vaccination of cows with fibrinogen-binding region A induced a strong and
      specific antibody response to ClfA in comparison with a control group injected
      with the pCI vector alone. Although the co-expression of both genetic adjuvants
      and the addition copolymer transporter did not augment the overall antibody
      response, these approaches decreased the number of non-responsive cows. Chitosan
      was the only factor that did not enhance the immune response. Three months after
      the last DNA immunization, three cows from each of the pGM-CSF, internal
      ribosomal entry site (IRES), pCTLA and pCI groups were injected with 200 microg
      of recombinant ClfA protein in incomplete Freund's adjuvant. A strong humoral
      response was observed in all groups following this protein boost, with the
      response occurring slightly earlier in DNA-primed protein boost cows. Sera and
      milk samples taken from cows after the second DNA injection or after the protein
      boost (sera only) were analyzed for their ability to block adherence and increase
      phagocytosis. Pre-incubation of S. aureus with sera or milk from vaccinated cows
      significantly reduced the pathogen's ability to adhere to MAC-T cells relative to
      the sera and milk samples from the pCI-injected control cows. Similarly, pools of
      sera and milk from vaccinated cows increased phagocytosis of S. aureus by
      neutrophils. After the protein boost, sera were more efficient promoters of
      phagocytosis, reflecting the higher anti-ClfA antibody level of these sera. DNA
      prime/protein boost regimes combined with molecular adjuvants appeared to be
      effective in generating a strong immune response to S. aureus antigens in cattle.

PMID- 16426714
TI  - Racializing narratives: obesity, diabetes and the "Aboriginal" thrifty genotype.
AB  - This post-colonial reading of narratives of obesity, diabetes, and the
      hypothesized "thrifty genotype" ascribed to Aboriginal peoples shows how
      scientific and popular texts support the belief in biological "race." Although
      the scientific consensus is that "race" is not a empirical category, many
      scientists use it without comment as a "crude proxy" for presumed genetic
      differences. The division between science and the social sciences/humanities
      protects such confusing practices from full scientific and social critique,
      something interdisciplinary research teams, science studies and improved peer
      review could provide.

PMID- 16426715
TI  - Exposure to indoor air pollution from household energy use in rural China: the
      interactions of technology, behavior, and knowledge in health risk management.
AB  - Indoor air pollution (IAP) from household use of biomass and coal is a leading
      environmental health risk in many developing nations. Much of the initial
      research on household energy technology overlooked the complex interactions of
      technological, behavioral, economic, and infrastructural factors that determine
      the success of environmental health interventions. Consequently, despite enormous
      interest in reducing the large and inequitable risks associated with household
      energy use in international development and global health, there is limited
      empirical research to form the basis for design and delivery of effective
      interventions. We used data from four poor provinces in China (Gansu, Guizhou,
      Inner Mongolia, and Shaanxi) to examine the linkages among technology, user
      knowledge and behavior, and access and infrastructure in exposure to IAP from
      household energy use. We conclude that broad health risk education is
      insufficient for successful risk mitigation when exposure behaviors are closely
      linked to day-to-day activities of households such as cooking and heating, or
      have other welfare implications, and hence cannot be simply stopped. Rather,
      there should be emphasis on the economic and infrastructure determinants of
      access to technology, as well as the details of behaviors that affect exposure.
      Better understanding of technology-behavior interface would also allow designing
      technological interventions that account for, and are robust to, behavioral
      factors or to provide individuals and households with alternative behaviors.
      Based on the analysis, we present technological and behavioral interventions for
      these four Chinese provinces.

PMID- 16426716
TI  - 'It's only a blood test': what people know and think about venepuncture and
      blood.
AB  - Medicine finds human blood infinitely useful. It is a source of important and
      sometimes controversial information about individuals, their relatives and the
      general public. Blood also has economic value, carries a heavy cultural freight,
      and can transmit dangerous diseases. Yet there is precious little sociological
      analysis of how these radically different applications, potentials and
      significations are managed in health care settings where, it is no exaggeration
      to claim, everyday a vast quantity of blood is produced by venepuncture. This
      paper focuses on blood produced in hospitals for tests. The data were derived
      from 19 focus groups of patients, health care professionals, and members of the
      public, held between 2002 and 2003, in and around the obstetrics and gynaecology
      department of a large London teaching hospital. Not surprisingly, all the
      participants had had a blood test at some time or other. Yet their responses
      suggest no template exists for talking about them. No-one--lay or professional-
      had a full picture of how blood produced for tests circulates around the
      hospital. Lay people tended to envisage it as remaining in a liquid form whereas
      health care professionals saw it as materially and substantially transformed.
      Participants deployed a variety of ritual and rhetorical devices that devalue
      blood produced for tests. Nonetheless, blood left over from tests emerged as a
      significant anomaly, simultaneously an excess (waste), a challenge (to use
      wisely), or a potential crime (illegitimate research).

PMID- 16426717
TI  - Physical violence by husbands: magnitude, disclosure and help-seeking behavior of
      women in Bangladesh.
AB  - This paper explores the magnitude of physical violence by husbands, the
      disclosure of it and the help-seeking behavior of abused women in urban and rural
      Bangladesh. The data come from a larger study on domestic violence against women
      conducted in Bangladesh during 2000-2004. All ever-married women covered by the
      population-based survey component (n=2702) conducted in 2001 were included in the
      current analysis. We also draw on in-depth interviews with 28 women who were
      physically abused by their husbands. Results show a high prevalence of lifetime
      physical spousal violence against women: 40% in urban and 42% in rural areas.
      Most of the abused women (66%) were silent about their experience. The main
      reasons behind this silence were high acceptance of violence, stigma and fear of
      greater harm. Sixty percent of urban and 51% of rural abused women never received
      any help from others. Only 2% ever sought help from institutional sources, from
      where support was not forthcoming. Women approached these sources only when they
      could not endure anymore or the violence became life threatening or children were
      at risk. The findings show that although providing appropriate services is
      absolutely necessary, it is also important to foster the use of such services and
      to help women overcome the barriers for accessing these services.

PMID- 16426718
TI  - Age perceptions and physical activity among middle-aged men in three occupational
      groups.
AB  - The aim of this study is to explore how middle-aged men in different socio
      economic groups and with different work experiences, talk about ageing, and how
      they see age as a reason for pursuing or not pursuing physical activity. Data
      were collected in Oslo by interviews with 46 men (carpenters, engineers, drivers)
      aged 35-57 years, and workplace group discussions. The analysis explored
      similarities and differences in the men's interpretive repertoires on work,
      everyday activities, health and health-related habits. The data were discussed in
      relation to Bourdieu's theories on the production and conversion of physical
      capital. For the carpenters emerging themes related to the ageing body were worry
      about decline in strength, the feeling of uselessness, and an awareness of what
      the body can take. For the engineers, the themes were keeping the body in shape
      and the ability to tackle stress. In addition to these themes, the drivers
      focussed on leaving the body as it is/taking age as it comes. Men in all three
      occupational groups said that they were thinking more about health and disease
      with age. Even though many talked about becoming more sedate, there were also
      some who maintained physical activity or became more physically active with age.
      The emphasis and the reasons for being more physically active were different in
      the three groups, and involved aspects such as health, strength, pleasure, social
      milieu, and warding off personal problems. Age was therefore used as a reason
      both for being and not being physically active. In conclusion health workers
      should be aware of the different life experiences and views related to the body,
      health and physical activity that exist among men of different occupational
      groups. This is needed to tailor information to fit the interest areas of men
      belonging to different socio-economic groups.

PMID- 16426720
TI  - Elevated serum superoxide dismutase and thiobarbituric acid reactive substances
      in schizophrenia: a study of patients treated with haloperidol or clozapine.
AB  - There is strong evidence that oxygen free radicals may play an important role in
      the pathophysiology of schizophrenia. Impaired antioxidant defense and increased
      lipid peroxidation have been previously reported in drug-naive, first episode and
      chronically medicated schizophrenic patients using typical neuroleptics. We
      measured serum SOD and TBARS in two groups of chronic medicated DSM-IV
      schizophrenic patients, under haloperidol (n = 10) or clozapine (n = 7) and a
      group of healthy controls (n = 15). Serum SOD and TBARS were significantly higher
      (p = 0.001) in schizophrenic patients (7.1 +/- 3.0 and 3.8 +/- 0.8) than in
      controls (4.0 +/- 1.6 and 2.5 +/- 0.7). Among patients, serum TBARS was
      significantly higher (p = 0.008) in those under clozapine (4.4 +/- 0.7) than in
      those under haloperidol treatment (3.4 +/- 0.7). For SOD levels the difference
      between groups was not found. It is reasonable to argue that the difference found
      in TBARS levels might be due to the course of the disease, instead of medication.
      Further investigation on the role of oxidative tonus and lipid peroxidation in
      different schizophrenia subtypes and different outcome patterns in this disorder
      is warranted. Additionally it could also address questions concerning a possible
      oxidant/antioxidant imbalance in schizophrenia.

PMID- 16426719
TI  - Event-related fMRI of category learning: differences in classification and
      feedback networks.
AB  - Eighteen healthy young adults underwent event-related (ER) functional magnetic
      resonance imaging (fMRI) of the brain while performing a visual category learning
      task. The specific category learning task required subjects to extract the rules
      that guide classification of quasi-random patterns of dots into categories.
      Following each classification choice, visual feedback was presented. The average
      hemodynamic response was calculated across the eighteen subjects to identify the
      separate networks associated with both classification and feedback. Random
      effects analyses identified the different networks implicated during the
      classification and feedback phases of each trial. The regions included prefrontal
      cortex, frontal eye fields, supplementary motor and eye fields, thalamus,
      caudate, superior and inferior parietal lobules, and areas within visual cortex.
      The differences between classification and feedback were identified as (i)
      overall higher volumes and signal intensities during classification as compared
      to feedback, (ii) involvement of the thalamus and superior parietal regions
      during the classification phase of each trial, and (iii) differential involvement
      of the caudate head during feedback. The effects of learning were then evaluated
      for both classification and feedback. Early in learning, subjects showed
      increased activation in the hippocampal regions during classification and
      activation in the heads of the caudate nuclei during the corresponding feedback
      phases. The findings suggest that early stages of prototype-distortion learning
      are characterized by networks previously associated with strategies of explicit
      memory and hypothesis testing. However as learning progresses the networks
      change. This finding suggests that the cognitive strategies also change during
      prototype-distortion learning.

PMID- 16426721
TI  - Cytosolic and localized inhibition of phosphodiesterase by atrazine in swine
      tissue homogenates.
AB  - Atrazine (ATR) significantly inhibited phosphodiesterase (PDE) in crude
      homogenates of swine heart, brain, and lung, but not liver or kidney tissues.
      Except for heart, PDE activities in the cytosolic fraction of the tissue
      homogenates were not affected by ATR. The inhibition of the PDE activity in the
      cytosol from heart homogenate was not significantly different between ATR and a
      non-specific PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Dixon plots of
      the crude tissue homogenates showed that heart and brain were inhibited via two
      different mechanisms (competitive or mixed inhibition, and noncompetitive
      inhibition, respectively), suggesting that ATR may be a semi-specific PDE
      inhibitor. Furthermore, in crude tissue homogenates, ATR did not inhibit PDE as
      effectively as IBMX suggesting that there are ATR-susceptible and ATR
      nonsusceptible forms of PDE. Association constants for ATR were 55 microM for
      heart and 310 microM for brain. The stability of the activity of PDE was affected
      by freezing, requiring the use of only freshly prepared tissue homogenates.

PMID- 16426723
TI  - Sub-chronic (13-week) oral toxicity study in rats with recombinant human
      lactoferrin produced in the milk of transgenic cows.
AB  - The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of
      transgenic cows was investigated in Wistar rats by daily administration via oral
      gavage for 13 consecutive weeks, 7 days per week. The study used four groups of
      20 rats/sex/dose. The control group received physiological saline and the three
      test groups received daily doses of 200, 600 and 2000 mg of rhLF per kg body
      weight. Clinical observations, growth, food consumption, food conversion
      efficiency, water consumption, neurobehavioural testing, ophthalmoscopy,
      haematology, clinical chemistry, renal concentration test, urinalysis, organ
      weights and gross examination at necropsy and microscopic examination of various
      organs and tissues were used as criteria for detecting the effects of treatment.
      Overall, no treatment-related, toxicologically significant changes were observed.
      The few findings that may be related to the treatment (lower cholesterol in high
      dose females, lower urinary pH in high-dose males and females and very slightly
      higher kidney weight in high-dose females) were considered of no toxicological
      significance. Based on the absence of treatment-related, toxicologically relevant
      changes, the no-observed-adverse-effect level (NOAEL) was considered to be at
      least 2000 mg/kg body weight/day.

PMID- 16426722
TI  - Punica granatum (pomegranate) flower extract possesses potent antioxidant
      activity and abrogates Fe-NTA induced hepatotoxicity in mice.
AB  - Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to
      possess enormous antioxidant activity. The present study evaluated antioxidant
      and hepatoprotective activity of pomegranate flowers. Alcoholic (ethanolic)
      extract of flowers was prepared and used in the present study. The extract was
      found to contain a large amount of polyphenols and exhibit enormous reducing
      ability, both indicative of potent antioxidant ability. The extract showed 81.6%
      antioxidant activity in DPPH model system. The ability of extract to scavenge
      reactive oxygen species (ROS) and reactive nitrogen species (RNS) was tested and
      it was found to significantly scavenge superoxide (O(2)(.-)) (by up to 53.3%),
      hydrogen peroxide (H(2)O(2)) (by up to 30%), hydroxyl radicals (()OH) (by up to
      37%) and nitric oxide (NO) (by up to 74.5%). The extract also inhibited (.)OH
      induced oxidation of lipids and proteins in vitro. These results indicated
      pomegranate flower extract to exert a significant antioxidant activity in vitro.
      The efficacy of extract was tested in vivo and it was found to exhibit a potent
      protective activity in acute oxidative tissue injury animal model: ferric
      nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Intraperitoneal
      administration of 9 mg/kg body wt. Fe-NTA to mice induced oxidative stress and
      liver injury. Pretreatment with pomegranate flower extract at a dose regimen of
      50-150 mg/kg body wt. for a week significantly and dose dependently protected
      against Fe-NTA induced oxidative stress as well as hepatic injury. The extract
      afforded up to 60% protection against hepatic lipid peroxidation and preserved
      glutathione (GSH) levels and activities of antioxidant enzymes viz., catalase
      (CAT), glutathione peroxidase (GPX) glutathione reductase (GR) and glutathione-S
      transferase (GST) by up to 36%, 28.5%, 28.7%, 40.2% and 42.5% respectively. A
      protection against Fe-NTA induced liver injury was apparent as inhibition in the
      modulation of liver markers viz., aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and albumin in
      serum. The histopathological changes produced by Fe-NTA, such as ballooning
      degeneration, fatty changes, necrosis were also alleviated by the extract. These
      results indicate pomegranate flowers to possess potent antioxidant and
      hepatoprotective property, the former being probably responsible for the latter.

PMID- 16426724
TI  - RNAi in mice: a promising approach to decipher gene functions in vivo.
AB  - RNA interference (RNAi) is a simple and powerful tool widely used to study gene
      functions in many species. Vector-based systems using RNA polymerase III
      promoters have been developed to achieve stable expression of small interfering
      RNA (siRNA) or small hairpin RNA (shRNA) in mammalian cells. Recent
      investigations demonstrated that when, combined with the Cre-loxP system, the
      vector-based RNAi can be used to achieve conditional or tissue specific knockdown
      of endogenous genes with high efficiency in mice. Here, we review these recent
      progresses and discuss the advantages, limitations and future development of this
      emerging technology.

PMID- 16426725
TI  - Relationship between urinary albumin and serum soluble fms-like tyrosine kinase 1
      (sFlt-1) in normal pregnancy.
AB  - OBJECTIVE: To investigate if the circulating level of soluble fms-like tyrosine
      kinase 1 (sFlt-1) and vascular endothelial growth factor (VEGF) correlates with
      urinary albumin excretion in normal pregnancy. STUDY DESIGN: Serum specimens and
      24h urine collections were requested from normal pregnant women at 28-30 weeks of
      gestation and the following laboratory tests were performed: serum creatinine,
      urinary protein, urinary albumin and creatinine clearance. For the present study,
      117 normal pregnant women were selected as subjects. Subjects' serum was tested
      to determine sFlt-1 and VEGF concentrations by ELISA. The correlation between
      sFlt-1 or VEGF concentrations in the serum and renal laboratory variables were
      analyzed. Simple regression was used to evaluate the correlations. RESULTS: A
      significant association was noted between serum sFlt-1 concentration and urinary
      albumin excretion (r=0.68; P<.0001). Similarly, a significant association was
      noted between serum VEGF concentration and urinary albumin excretion (r=-0.39;
      P<.0001). Other urinary variables showed no correlations with either sFlt-1 or
      VEGF. CONCLUSION: Even in normal pregnancy, albumin excretion is affected by an
      increase in placentally derived sFlt-1. If the sFlt-1 level is kept within normal
      range, only glomerular endothelial cells are affected and this phenomenon does
      not spread to the endothelial cells of a whole body.

PMID- 16426726
TI  - MRSA in urology: a UK hospital experience.
AB  - OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) infection appears
      to be increasing, the UK has one of the worst MRSA rates in Europe. As urological
      patients are at high risk, the aim of this study was to determine the number of
      newly diagnosed cases of MRSA detected in a urology ward. PATIENTS AND METHODS:
      The urology department serves an annual local population of greater than 500,000
      with 30 inpatient beds and a tertiary population of 1 million. Over a five year
      period, we retrospectively recorded all patients with a new diagnosis of MRSA. We
      also determined colonization site and if the diagnosis of MRSA was made in an
      elective surgical patient or a patient admitted as an emergency. RESULTS: The
      mean number of newly diagnosed cases of MRSA was 20.6 per year. The percentage of
      patients with a new diagnosis of MRSA was less than or equal to 1% per year with
      no significant difference of new cases of MRSA over five years. Emergency
      patients had a trend towards a mean higher rate of MRSA. The commonest site of
      MRSA colonization was from catheters (32%) and open wounds (18%). DISCUSSION:
      MRSA is of concern, as compared to methicillin-sensitive staphylococcus aureus,
      because it is associated with high rates of clinically relevant infection,
      increased hospital stay and cost, greater mortality and high vancomycin usage.
      Mandatory reporting has shown a steady increase in the number of cases of MRSA
      infection over the past four years. We found that the number of newly diagnosed
      cases of MRSA was low, at less than or equal to 1% of patients per year.
      Furthermore, the number of new cases of MRSA remained constant over five years
      suggesting low acquisition rates in a busy UK urology ward.

PMID- 16426727
TI  - Treatment of varicocele in subfertile men: The Cochrane Review--a contrary
      opinion.
AB  - OBJECTIVE: A recent Cochrane meta-analysis of randomised clinical trials (RCTs)
      concluded that surgical or radiological treatment of varicocele in men from
      couples with otherwise unexplained subfertility cannot be recommended. The aim of
      the present study is to address criticisms of this review carrying out a critical
      analysis of all available RCTs. MATERIALS AND METHODS: The eight randomised
      clinical trials selected in the last Cochrane Library systematic review have been
      evaluated. All RCTs including patients either with normal semen analysis or
      subclinical varicocele have been excluded. Inclusion criteria, number and
      clinical characteristics of randomised patients, and outcomes reported in terms
      of pregnancy rate one year after randomisation have been described in the
      remaining studies. RESULTS: Only 3/8 RCTs included patients with abnormal semen
      analysis and palpable varicocele. Overall 120 patients in the treatment group and
      117 in the control group were randomised. The studies turned out to be
      heterogeneous in terms of inclusion criteria and clinical characteristics of the
      analysed patients. Their methodological quality and statistical power have to be
      considered poor. Moreover, the "as treated" cumulative analysis showed a
      significant increase in pregnancy rate in patients who underwent varicocele
      treatment (36.4%) compared with the control group (20%) (p = 0.009). CONCLUSIONS:
      The RCTs included in the last Cochrane review concerning the efficacy of
      varicocele treatment in subfertile couples were heterogeneous and
      methodologically poor. The pooling of these studies cannot result in a good
      quality meta-analysis. The Cochrane meta-analysis conclusions should not support
      guidelines recommendation against varicocele treatment in subfertile patients.
      Data from ongoing studies should provide more information in this topic.

PMID- 16426728
TI  - The prognostic value of E-cadherin, alpha-, beta-, and gamma-catenin in
      urothelial cancer of the upper urinary tract.
AB  - OBJECTIVES: To determine the value of loss of the expression of E-cadherin and
      cadherin-associated molecules as useful markers for both prognosis and bladder
      recurrence in patients with upper urinary tract cancer. MATERIALS AND METHODS: In
      61 paraffin-embedded nephroureterectomy specimens, the expression of E-cadherin
      and alpha-, beta-, and gamma-catenin was examined by immunohistochemical
      staining. To evaluate the prognostic significance, Kaplan-Meier survival curves
      were calculated and compared by the log-rank test. A multivariate test was
      performed to detect prognostic markers. RESULTS: Normal expression was found in
      32 cases (52.5%) for E-cadherin, 41 cases (67.2%) for alpha-catenin, 42 cases
      (68.9%) for beta-catenin, and 31 cases (50.8%) for gamma-catenin. The expression
      patterns of E-cadherin and alpha-, beta- and gamma-catenin were significantly
      correlated with each other. Survival analysis showed a significant difference
      between normal and aberrant expression in each staining. Multivariate analysis
      revealed that tumor stage and the expression of E-cadherin were independent
      prognostic factors for cause-specific survival. In contrast, there was no
      significant correlation between the expression of E-cadherin and alpha-, beta-,
      and gamma-catenin and bladder recurrence. CONCLUSION: Our data suggest E-cadherin
      may be a good prognostic marker for patients with upper urinary tract cancer.

PMID- 16426730
TI  - Association of mast cells with microvessel density in renal cell carcinomas.
AB  - BACKGROUND: Growth of solid tumors requires angiogenesis. Evidence indicates that
      mast cells (MCs) play an important role in tumor angiogenesis. The aim of this
      study was to investigate the possible effects of angiogenesis and the presence of
      MCs on the prognosis of renal cell carcinoma (RCC). METHODS: Seventy-one patients
      who underwent radical nephrectomy for RCC were included in this study. Paraffin
      sections from tumor and nonneoplastic kidney were stained with CD31 antibody with
      the standard streptavidin-biotin immunperoxidase method. Microvessels were
      quantified by a stereologic method. Tumors and the surrounding area were also
      stained with toludine blue stain to show MCs in tumor and surrounding tissue. The
      correlation between microvessels and MC counts was evaluated and compared with
      tumor stage, grade, and other clinicopathologic parameters. RESULTS: MCs in RCC
      and peritumoral areas were observed to be greater than nonneoplastic kidney
      tissue. No correlation was found between MC number and various clinicopathologic
      features such as tumor size, stage, grade, and patient survival. No association
      was noted between angiogenesis and clinicopathologic features. On the other hand,
      significant correlation was found between the number of MCs and microvessel
      density (p=0.034, r=0.295). CONCLUSION: Our results suggest that MC infiltration
      may contribute to tumor angiogenesis and acceleration of tumor growth, whereas
      stereologic assessment of angiogenesis does not help to predict biologic behavior
      in RCC. Further research is required to confirm these observations.

PMID- 16426729
TI  - Intravesical instillations with bacillus calmette-guerin for the treatment of
      carcinoma in situ involving prostatic ducts.
AB  - OBJECTIVES: Bacillus Calmette-Guerin (BCG) has proven its efficacy in the
      treatment of carcinoma in situ (CIS) of the prostatic urethra. We performed a
      retrospective study to evaluate the use of intravesical instillations of BCG in
      patients with carcinoma in situ involving prostatic ducts after complete
      transurethral resection (TUR). MATERIAL AND METHODS: Eligibility for the study
      was CIS of the prostatic urethra involving prostatic ducts. Previous instillation
      with BCG was an exclusion criterion. Patients were treated with intravesical BCG
      Connaught (81 mg) administered once a week, over a 6-wk period. TUR loop biopsies
      of the prostate were performed only when a macroscopic tumor was present.
      RESULTS: In this retrospective study of 11 patients, 8 (73%) presented with
      macroscopic tumor in the prostatic urethra. Ten patients (91%) had a simultaneous
      superficial bladder carcinoma. Eight patients (73%) had tumoral involvement of
      the bladder neck region. After a median follow-up of 27 mo (n=10 patients), the
      response in the prostatic urethra was 82%, and the response in the bladder due to
      superficial tumor recurrence was 64%. Two patients with residual ductal disease
      in the prostatic urethra were subsequently treated with cystoprostatectomy and
      are currently free of disease. In one of those patients, the cystoprostatectomy
      specimen did show prostatic stromal invasion. Another patient developed distant
      metastatic disease and died a few months after diagnosis. Thus, progression was
      encountered in two patients (18%). Currently, 90% of patients are alive without
      evidence of disease and 72.7% have benefitted from this bladder preservation
      strategy. CONCLUSION: Intravesical BCG is a feasible treatment option for
      patients with CIS involving prostatic ducts. In this retrospective study, bladder
      preservation was successful in 8 of 11 patients (70%) and there was only one
      oncologic death. Obviously, these patients need a careful follow-up with
      cystoscopy and cytology to detect either recurrence or progression and in those
      with persistent disease after the initial BCG induction therapy, prompt
      cystectomy is indicated.

PMID- 16426731
TI  - Sensitivity and detection rate of a 12-core trans-perineal prostate biopsy:
      preliminary report.
AB  - OBJECTIVES: The various prostate biopsy methods are usually compared in terms of
      the diagnosis rate of prostate cancer. However, the prevalence of cancer in
      patients with a negative prostatic biopsy is not usually known. We determined the
      sensitivity and detection rate of 12-core transperineal biopsies in patients not
      previously investigated for prostate cancer. METHODS: We performed prostate
      biopsy in 63 patients (median age 67 years) before radical cystoprostatectomy for
      high-grade bladder cancer. We then assessed the relationships between biopsy
      result, prostate cancer in the surgical specimen, and other variables. RESULTS:
      17.2% of patients had a positive biopsy and 54% had prostate cancer on definitive
      histology. Biopsy sensitivity was 32.3% overall, 75% for clinically significant
      cancers, and 11% for non-significant cancers. Median PSA was 1.2ng/ml, PSA levels
      did not correlate with the presence of prostate cancer, the presence of
      clinically significant cancer, bioptic diagnosis, or prostate volume. Age
      correlated with risk of cancer. CONCLUSIONS: According to autopsy series, the
      prevalence of prostate cancer is greater than 50% in males older than 60, yet low
      PSA levels do not reliably indicate disease absence. The sensitivity of double
      sextant biopsy is unsatisfactory overall (32%), but acceptable (75%) for
      diagnosing clinically significant cancer.

PMID- 16426732
TI  - Tachykinins: role in detrusor overactivity?

PMID- 16426733
TI  - Watchful waiting for low-grade Ta bladder tumours: the idea would have been
      unacceptable 30 years ago, but nowadays we are highly interested in the results
      of this study exploring it.

PMID- 16426734
TI  - Proposed mechanism for the efficacy of injected botulinum toxin in the treatment
      of human detrusor overactivity.
AB  - BACKGROUND: Treatment of human bladder overactivity with intradetrusor Botulinum
      A neurotoxin (BoNT/A) injections temporarily blocks the presynaptic release of
      acetylcholine from the parasympathetic innervation and produces a paralysis of
      the detrusor smooth muscle. The efficacy of the treatment exceeds that expected
      from simple detrusor muscle paralysis, however, and its effect of reducing
      urgency is greatly welcomed by patients. OBJECTIVES: To examine whether BoNT/A
      has a complex effect on sensory mechanisms by inhibiting vesicular release of
      multiple excitatory neurotransmitters by urothelial and suburothelial nerves and
      reducing axonal expression of SNARE-complex dependent proteins. METHODS: A
      literature review. CONCLUSIONS: We propose that a primary peripheral effect of
      BoNT/A is the inhibition of release of acetylcholine, ATP, substance P, and
      reduction in the axonal expression of the capsaicin and purinergic receptors.
      This may be followed by central desensitization through a decrease in central
      uptake of substance P and neurotrophic factors. The summation of these effects is
      a profound and long-lasting inhibition of those afferent and efferent mechanisms
      that are thought to be the pathophysiological basis for DO.

PMID- 16426735
TI  - Quality of life changes in patients with neurogenic versus idiopathic detrusor
      overactivity after intradetrusor injections of botulinum neurotoxin type A and
      correlations with lower urinary tract symptoms and urodynamic changes.
AB  - OBJECTIVE: Little published data exist on the effect of intradetrusor botulinum
      neurotoxin type A (BoNT/A) on the quality of life (QOL) of patients with
      overactive bladder. We examined post-BoNT/A QOL changes of patients with
      neurogenic detrusor overactivity (NDO) in comparison to those with idiopathic
      detrusor overactivity (IDO), and their correlations with respective changes in
      lower urinary tract symptoms (LUTS) and urodynamic parameters. METHODS: Patients
      with urodynamically proven intractable DO were assessed for changes in QOL 4 and
      16 wk after treatment with intradetrusor BOTOX injections (NDO 300U; IDO 200U)
      using the short forms of the Urinary Distress Inventory (UDI-6) and Incontinence
      Impact Questionnaire (IIQ-7). Percent changes in total QOL score were correlated
      to respective changes in clinical parameters recorded by bladder diaries and
      voiding cystometry. RESULTS: Forty-eight treated patients (32 NDO, 16 IDO) had
      QOL data in at least one follow-up. Highly significant decreases (p < 0.0001) in
      mean +/- standard error QOL score at 4 wk were maintained at 16 wk for both the
      NDO and IDO subgroups. Percent improvement in QOL score was similar for NDO
      versus IDO at 4 (67.6 +/- 4.5 versus 70.3 +/- 7.7, p = 0.74) and 16 wk (65.2 +/-
      5.5 versus 71.9 +/- 8.8, p = 0.51). Percent changes in QOL score of the whole
      patient group correlated with changes in 24-h micturition frequency, number of
      voids associated with urgency, and number of urge incontinence episodes, but not
      with urodynamic parameters. CONCLUSIONS: Intradetrusor BoNT/A produces
      comparable, significant improvements in the QOL of patients with either NDO or
      IDO at least up to 16 wk after treatment. In contrast to urodynamic parameters,
      changes in LUTS appear to be the major determinants of improvements in the
      patients' QOL.

PMID- 16426736
TI  - Expression of COX-2 in normal and pyelonephritic kidney, renal intraepithelial
      neoplasia, and renal cell carcinoma.
AB  - OBJECTIVES: The role of inflammation in carcinogenesis is unknown. To determine
      the relationship between cyclooxygenase 2 (COX-2) expression, inflammation, and
      carcinogenesis in human renal cell carcinoma (RCC), we looked for COX-2
      expression in normal and pyelonephritic kidney, renal intratubular neoplasia
      (RIN), and RCC tissues. METHODS: COX-2 expression was assessed
      immunohistochemically in tissues obtained from 20 pyelonephritic kidneys, 16
      normal kidneys, 19 RIN, and 75 RCC cases. RESULTS: COX-2 expression was found to
      be positive in 64% of RCCs. It was positive in 13 chronic pyelonephritic (65%), 9
      normal (56%), and 15 RIN (79%) cases. COX-2 expression was significantly higher
      in RCC and RIN than the normal and pyelonephritic cases (p<0.001 and p<0.001,
      respectively). No statistically significant difference was noted between RCC and
      RIN cases. CONCLUSIONS: Although the function of COX-2 in tumor development has
      not been exactly elucidated, the increased expression of COX-2 in RIN and RCC
      might be a factor that may play a role in the development of RIN or progression
      to RCC, which warrants further research.

PMID- 16426737
TI  - Prognostic and biological significance of lymph node spreading in renal cell
      carcinoma.

PMID- 16426738
TI  - The bell-shaped nitinol prostatic stent in the treatment of lower urinary tract
      symptoms: experience in 108 patients.
AB  - OBJECTIVES: To assess the efficacy, safety, and durability of the bell-shaped
      nitinol prostatic stent in the treatment of moderate to severe lower urinary
      tract symptoms caused by benign prostatic enlargement in otherwise healthy
      patients. METHODS: Stents were inserted in an outpatient setting under local
      anaesthesia. Assessments included maximum urinary flow (Qmax), postvoid residual
      (PVR) urine volume, International Prostate Symptom Score (IPSS), including
      quality of life (QoL) item, at baseline and follow-up visits. RESULTS: 108 men
      were enrolled in the trial. Stents were successfully inserted in 97% of the
      patients. Spontaneous voiding was achieved in all patients. After one month Qmax
      (+3.7 ml/s), PVR (-99 ml), IPSS (-12) and QoL (-1.7) all showed statistically
      significant improvements compared to baseline. Substantial improvements, however,
      were maintained for only one to two months. The main complications were
      haematuria (19%), urge incontinence (22%), and migration (15%). The median
      indwelling time was 105 days. The main reason for removal of stents was worsening
      of symptoms, which might be attributable to the tilting of stents within the
      prostatic urethra, found upon removal. CONCLUSIONS: Insertion of the bell-shaped
      nitinol prostatic stent temporarily improves voiding parameters and symptom
      scores. Because of the limited durability, however, the bell-shaped prostatic
      stent is not suitable for clinical practice.

PMID- 16426739
TI  - Staging system of renal cell carcinoma: current issues.

PMID- 16426740
TI  - Cancer: a Systems Biology disease.
AB  - Cancer research has focused on the identification of molecular differences
      between cancerous and healthy cells. The emerging picture is overwhelmingly
      complex. Molecules out of many parallel signal transduction pathways are
      involved. Their activities appear to be controlled by multiple factors. The
      action of regulatory circuits, cross-talk between pathways and the non-linear
      reaction kinetics of biochemical processes complicate the understanding and
      prediction of the outcome of intracellular signaling. In addition, interactions
      between tumor and other cell types give rise to a complex supra-cellular
      communication network. If cancer is such a complex system, how can one ever
      predict the effect of a mutation in a particular gene on a functionality of the
      entire system? And, how should one go about identifying drug targets? Here, we
      argue that one aspect is to recognize, where the essence resides, i.e. recognize
      cancer as a Systems Biology disease. Then, more cancer biologists could become
      systems biologists aiming to provide answers to some of the above systemic
      questions. To this aim, they should integrate the available knowledge stemming
      from quantitative experimental results through mathematical models. Models that
      have contributed to the understanding of complex biological systems are
      discussed. We show that the architecture of a signaling network is important for
      determining the site at which an oncologist should intervene. Finally, we discuss
      the possibility of applying network-based drug design to cancer treatment and how
      rationalized therapies, such as the application of kinase inhibitors, may benefit
      from Systems Biology.

PMID- 16426741
TI  - Extracellular matrix integrity: a possible mechanism for differential clinical
      effects among selective estrogen receptor modulators and estrogens?
AB  - Recent gene microarray studies have illustrated heterogeneity in gene expression
      changes not only between estrogens and selective estrogen receptor modulators
      (SERMs), but also across different SERM molecules. In ovariectomized rats, this
      phenomenon was observed with respect to a number of genes involved in collagen
      turnover and extracellular matrix (ECM) integrity in the uterus and vaginal
      tissues. Preliminary mechanistic data suggest that these effects on ECM integrity
      may have relevance in the context of the effect of estrogens and some SERMs to
      increase the risk of pelvic organ prolapse and the incidence of urinary
      incontinence in postmenopausal women. Given the pivotal role of ECM integrity and
      collagen turnover in other tissues and disease states, these processes may
      provide a fruitful target for future research into the mechanisms for the
      heterogeneous pharmacology of estrogens and SERMs across different cell types and
      target tissues.

PMID- 16426743
TI  - Apoptotic and proliferation indexes in primary superficial bladder tumors.
AB  - Whether apoptotic index [AI] and/or Ki-67 labeling index [Ki-67LI] add prognostic
      information in bladder cancer remains unclear. Mean AI and Ki-67 LI increased
      with grade and stage in 147 superficial bladder tumors. AI (>1.7%) correlated
      with tumor size, grade and proliferation. Ki-67 LI (>10%) correlated with higher
      grade and stage. Tumor size and Ki-67 LI were independent predictors of disease
      free and progression-free survival, respectively. Tumor size, patient's age and
      tumor's recurrence predicted overall survival. We conclude that conventional
      clinical parameters and Ki-67 LI define risk groups of bladder tumors, while AI
      has limited value.

PMID- 16426742
TI  - Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability
      and DNA damage tolerance.
AB  - Inherited defects in genes associated with DNA mismatch repair (MMR) have been
      linked to familial colorectal cancer. Cells deficient in MMR are genetically
      unstable and demonstrate a tolerance phenotype in response to certain classes of
      DNA damage. Some sporadic human cancers also show abnormalities in MMR gene
      function, typically due to diminished expression of one of the MutL homologs,
      MLH1. Here, we report that overexpression of the MutL homolog, human PMS2, can
      also cause a disruption of the MMR pathway in mammalian cells, resulting in
      hypermutability and DNA damage tolerance. A mouse fibroblast cell line carrying a
      recoverable lambda phage shuttle vector for mutation detection was transfected
      with either a vector designed to express hPMS2 or with an empty vector control.
      Cells overexpressing hPMS2 were found to have elevated spontaneous mutation
      frequencies at the cII reporter gene locus. They also showed an increase in the
      level of mutations induced by the alkylating agent, methynitrosourea (MNU).
      Clonogenic survival assays demonstrated increased survival of the PMS2
      overexpressing cells following exposure to MNU, consistent with the induction of
      a damage tolerance phenotype. Similar results were seen in cells expressing a
      mutant PMS2 gene, containing a premature stop codon at position 134 and
      representing a variant found in an individual with familial colon cancer. These
      results show that dysregulation of PMS2 gene expression can disrupt MMR function
      in mammalian cells and establish an additional carcinogenic mechanism by which
      cells can develop genetic instability and acquire resistance to cytotoxic cancer
      therapies.

PMID- 16426744
TI  - Potentiation of cyclophosphamide chemotherapy using the anti-angiogenic drug
      thalidomide: importance of optimal scheduling to exploit the 'normalization'
      window of the tumor vasculature.
AB  - The aim of this work was to study how administration schedule affects
      potentiation of cyclophosphamide, an alkylating agent, by thalidomide, an anti
      angiogenic agent. Tumor oxygenation after thalidomide administration was
      determined over time by EPR oximetry. Such measurements provide a surrogate
      marker for determining the timing of 'normalization' of tumor vasculature. Re
      growth delays were measured using different combinations and schedules of
      treatments. Additionally, the uptake of the metabolite of cyclophosphamide
      (hydroxycyclophosphamide or OH-CP) into tumors was determined by high performance
      liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A significant
      increase in pO(2) was observed after 2 and 3 days of treatment before eventually
      declining on day 4. Thalidomide potentiated the effect of cyclophosphamide only
      when cyclophosphamide was administered after 2 days of treatment with thalidomide
      (no significant benefit using other schedules). In this time frame, the
      HPLC/MS/MS measurements showed that the quantity of OH-CP penetrating into the
      tumor was about twice in mice treated by thalidomide compared to controls. In
      conclusion, the present study demonstrates that the benefit of combined therapy
      using an anti-angiogenic agent with a cytotoxic agent requires knowledge of the
      time window during which the vessels initially become normalized.

PMID- 16426745
TI  - Surface modification of nanometer size TiO2 with salicylic acid for
      photocatalytic degradation of 4-nitrophenol.
AB  - The efficiency of photocatalytic reactions was limited by the wide band-gap of
      TiO(2) and the high degree of electron-hole recombination inherent in
      photocatalytic process, as well as by the limited adsorption capability of
      photocatalysts. In order to increase the overall efficiency, the surface of
      nanometer size TiO(2) was simply and fast modified by chemical adsorption in
      saturated solution of salicylic acid. A stable, light yellow surface complex was
      formed quickly, which has obvious absorption in the region from 320 to 420 nm.
      Through surface modification, the adsorption efficiency of 4-nitrophenol by
      TiO(2) was enhanced from 42 to 84%. The photocatalytic efficiency was tested on
      the degradation of 4-nitrophenol. The influences of catalyst and its dosage, pH
      value, and 4-nitrophenol concentration on the degradation were investigated.
      Under such photodegradation conditions as initial pH 4.0, 4-nitrophenol 5 mg l(
      1), catalyst 100 mg, and irradiation time 160 min with 160 W high-pressure
      mercury lamp, the degradation efficiency of 4-nitrophenol by TiO(2) was increased
      from 39.5 to 79.3% after surface modification, and furthermore, the degradation
      efficiency could be enhanced to 91.1% if the concentration of 4-nitrophenol was
      not more than 1 mg l(-1). Compared with the pure TiO(2), surface modification led
      not only to improve the surface coverage of 4-nitrophenol, but also to increase
      the light utilization. Both of these factors were crucial for the photocatalytic
      activity of heterogeneous photocatalysis, especially for photodegradation of
      aromatic pollutants.

PMID- 16426746
TI  - Evaluation of the interaction mechanisms between red muds and heavy metals.
AB  - This paper investigated the heavy metal adsorption of non-treated (RM(nt)) and
      acid-treated red muds (RM(a)), bauxite ore processing waste, in order to evaluate
      how efficient they are in reducing metal solubility and bioavaliability in
      polluted soils. Red mud samples were artificially polluted with solutions
      containing increasing concentrations of Pb, Cd and Zn. Cancrinite and hematite
      were the main phases of the red muds, and were also the components which adsorbed
      most heavy metals. The results showed that the RM(nt) adsorption capacity for the
      three heavy metals was Zn> or =Pb>Cd. Acid treatment with HCl decreased the red
      mud's capacity to adsorb the heavy metals by 30%. In order to study the different
      heavy metal-RM interaction mechanisms, all samples after artificial contamination
      were treated with solutions with gradually increasing extraction capacity. H(2)O
      and Ca(NO(3))(2) treatments only extracted very low concentrations of Pb, Cd and
      Zn, while EDTA treatment extracted the most adsorbed heavy metals from the
      sorbent particles. In particular the water-soluble and exchangeable metal
      fractions were higher in the RM(a) than they were in the RM(nt), while the
      concentrations of Pb, Cd and Zn extracted with EDTA were lower. The results
      showed that red muds can be used successfully to reduce the solubility and
      bioavailability of heavy metals in polluted soils.

PMID- 16426747
TI  - Modified softwood sawdust as adsorbent of heavy metal ions from water.
AB  - The sawdust of deciduous softwood-poplar, and coniferous softwood-fir, have been
      found to possess some adsorption capacities for heavy metal ions. Their
      adsorption capacities can be increased by previous treatment with a sodium
      hydroxide solution. Adsorption capacities of alkali modified adsorbents were
      higher than for unmodified ones from 2.5 to 5 times for copper ions, and about 15
      times for zinc ions. Also, for modification can be used solution of sodium
      carbonate, but that alkaline solution is less efficient than sodium hydroxide
      solution. The 1% sodium hydroxide solution is suggested for modification of
      softwood sawdust. It was established that the ion exchange is not only adsorption
      mechanism, than microprecipitation of metal-hydroxide in the pore liquid was
      happened, too. At the same time, the leaching of organic matters from modified
      softwood sawdust were less than from unmodified ones for about 7% for poplar and
      23% for fir.

PMID- 16426748
TI  - Generation of urban road dust from anti-skid and asphalt concrete aggregates.
AB  - Road dust forms an important component of airborne particulate matter in urban
      areas. In many winter cities the use of anti-skid aggregates and studded tires
      enhance the generation of mineral particles. The abrasion particles dominate the
      PM10 during springtime when the material deposited in snow is resuspended. This
      paper summarizes the results from three test series performed in a test facility
      to assess the factors that affect the generation of abrasion components of road
      dust. Concentrations, mass size distribution and composition of the particles
      were studied. Over 90% of the particles were aluminosilicates from either anti
      skid or asphalt concrete aggregates. Mineral particles were observed mainly in
      the PM10 fraction, the fine fraction being 12% and submicron size being 6% of
      PM10 mass. The PM10 concentrations increased as a function of the amount of anti
      skid aggregate dispersed. The use of anti-skid aggregate increased substantially
      the amount of PM10 originated from the asphalt concrete. It was concluded that
      anti-skid aggregate grains contribute to pavement wear. The particle size
      distribution of the anti-skid aggregates had great impact on PM10 emissions which
      were additionally enhanced by studded tires, modal composition, and texture of
      anti-skid aggregates. The results emphasize the interaction of tires, anti-skid
      aggregate, and asphalt concrete pavement in the production of dust emissions.
      They all must be taken into account when measures to reduce road dust are
      considered. The winter maintenance and springtime cleaning must be performed
      properly with methods which are efficient in reducing PM10 dust.

PMID- 16426749
TI  - Theoretical prediction of condensed phase heat of formation of nitramines,
      nitrate esters, nitroaliphatics and related energetic compounds.
AB  - An empirical approach is presented for calculation heats of formation of
      nitramines, nitrate esters, nitroaliphatics and related energetic compounds which
      contain at least one of the functional groups including N-NO(2), C-ONO(2) or
      nonaromatic C-NO(2). This approach is based on elemental composition and various
      structural and functional group parameters of C(a)H(b)N(c)O(d) energetic
      compounds. Heat of formation for 78 nitrocompounds including nitramines, nitrate
      esters, nitroaliphatics and the data obtained is compared with experimental data.
      Root mean square (rms) of deviation for 19 well known of mentioned energetic
      compounds are also compared with complex quantum mechanical computations which
      show 23.8 and 21.3 kJ/mol for new and quantum mechanical methods, respectively.
      Predicted condensed phase heats of formation for remainder 59 energetic molecules
      with complex molecular structures have a rms deviation from experiment of 42.3
      kJ/mol.

PMID- 16426750
TI  - Microwave enhanced-sorption of dyestuffs to dual-cation organobentonites from
      water.
AB  - The microwave enhanced-sorption of dyestuffs such as Neutral Red S-BR, Neutral
      Dark Yellow GL and Acid Blue B onto organobentonites from water was investigated.
      The decolorization rates of various dyestuffs by organobentonites were increased
      from 18.0% to 71.8%, the saturated sorption capacity of Neutral Red S-BR and Acid
      Blue B were increased 83.9% and 76.3% by microwave irradiation, respectively. The
      value of the microwave enhanced-sorption parameter R(m) increased in the
      following order: Neutral Red S-BR>Acid Blue B>Neutral Dark Yellow GL, which
      corresponded with their aqueous solubility. The zeta potentials of particles were
      decreased greatly by microwave, which is very significant for improving both
      sorption of dyestuffs to organobentonites from water and the separation of the
      adsorbents from treated water.

PMID- 16426751
TI  - Regulation of sympathetic and parasympathetic nerve activities by BIT/SHPS-1.
AB  - The hypothalamus plays a central role in the homeostatic regulation of internal
      physiological conditions such as body temperature and energy balance. We have
      previously shown that cold exposure enhances tyrosine phosphorylation of BIT/SHPS
      1 (brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP
      substrate-1) in hypothalamic nuclei including the suprachiasmatic nucleus. In
      order to elucidate the function of BIT/SHPS-1 in the hypothalamus, we stimulated
      BIT/SHPS-1 in vivo by using the anti-BIT monoclonal antibody (mAb) 1D4, which
      reacts with the extracellular domain of BIT/SHPS-1 and induces its tyrosine
      phosphorylation. Administration of mAb 1D4 into the third cerebral ventricle
      enhanced the electrical activity of the renal sympathetic nerves, while it
      suppressed that of the gastric parasympathetic nerves. Similarly, blood pressure
      increased in response to the mAb 1D4 injection, and additionally, temperatures of
      the abdomen and brown adipose tissue increased. These results indicate that
      BIT/SHPS-1 is involved in the hypothalamic regulation of thermogenesis via the
      autonomic nervous system.

PMID- 16426752
TI  - The posture-related interaction between Ia-afferent and descending input on the
      spinal reflex excitability in humans.
AB  - The separate and combined depressive effects induced by vibration and standing on
      the soleus H-reflex have been studied by administering Achilles' tendon vibration
      in prone position and during stance. Without vibration, H-reflex amplitude was
      larger under prone than standing condition. Vibration reduced the reflex both in
      prone position and even more during stance. When vibration was superimposed to
      inclined stance (greater EMG background), the reflex was reduced of the same
      absolute amount as when it was superimposed to normal stance. When vibration was
      superimposed on stance with minimal or no background EMG, the reflex disappeared.
      These results confirm that both upright posture and vibration have a strong
      depressive effect on the H-reflex. They also show that muscle activity during
      stance is enough for overcoming the reflex depression. These findings provide
      information about the origin of the disfacilitatory effects on the monosynaptic
      reflex pathway, contribute to the understanding of the posture-related mechanisms
      responsible for the modulation of the spinal reflex excitability, and allow
      arguing in favour of a minor but adaptable role for the short latency stretch
      reflex in the control of quiet unperturbed stance.

PMID- 16426753
TI  - Activation of ATP-sensitive K channels protects hippocampal CA1 neurons from
      hypoxia by suppressing p53 expression.
AB  - Oxygen-sensing and responses to changes in oxygen concentration is a fundamental
      property of cellular physiology. In the central nervous system (CNS), hippocampal
      CA1 neurons are known to be extremely vulnerable to low oxygen concentrations or
      anoxia. Understanding the mechanisms governing tolerance to oxygen depletion is
      vital for developing strategies to protect the brain from hypoxic-ischemic
      insult. Our current study demonstrates the protective mechanism of KATP channels
      on hippocampal CA1 neurons subjected to hypoxic or anoxic conditions.
      Specifically, we show that CA1 neurons undergo apoptosis when depleted of oxygen
      for 12 or 24 h. A KATP channels agonist diazoxide inhibits the observed
      apoptosis. The inhibition of apoptosis is mediated through diazoxide's ability to
      reduce p53 expression. On the other hand, tolbutamide, a KATP channels antagonist
      which blocks the cellular sulphonylureas receptor, significantly increases p53
      expression and apoptosis under hypoxic/anoxic conditions. Trichostatin (TSA), a
      p53 inhibitor, can block the effects of tolbutamide, lending further support for
      a role of p53 in mediating this process. These studies demonstrate that KATP
      channels act as an upstream antagonist of p53 in hippocampal CA1 neurons, and
      suggests their protective role in cerebral hypoxia.

PMID- 16426754
TI  - Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports.
AB  - Electrical stimulation of the cerebellar cortex by implanted electrodes has been
      shown to ameliorate refractory epilepsy. We investigated the potential
      therapeutic role of high-frequency cerebellar rTMS in patients affected by
      refractory epilepsy due to single or multiple foci. Six patients, three with
      single and three with multiple epileptic foci, underwent 20 rTMS sessions. Each
      session was given daily, excluding weekends, and consisted of two trains of 50
      stimuli (5 Hz frequency and 90% motor threshold intensity), separated by 50s
      interval. rTMS was delivered through a focal coil (2 cm below and lateral to the
      inion) bilaterally in patients with multiple foci (two trains for hemisphere: 100
      stimuli each side) and contralaterally to the epileptic focus in the others.
      Seizure frequency was monitored four weeks before stimulation (pre-rTMS), during
      the four-week treatment (rTMS) and four weeks after the treatment (post-rTMS).
      The rTMS over the cerebellar cortex was associated with a significant decrease of
      rTMS versus pre-rTMS seizure frequency both in patients with single and multiple
      epileptic foci. However, during the post-rTMS period seizure frequency was back
      to the pre-rTMS frequency. Although the results are still preliminary, they
      encourage further studies on larger series of patients. In particular, this rTMS
      approach, as compared with others, might be more useful in patients with multiple
      epileptic foci.

PMID- 16426755
TI  - Indices of low-grade chronic inflammation correlate with early cognitive
      deterioration in an elderly Greek population.
AB  - Elevated serum levels of adhesion molecules (AM) reflect low-grade chronic
      inflammation and have been associated with several conditions of neuronal damage.
      The aim of the present study was the investigation of possible correlation
      between early cognitive decline and inflammatory processes in the elderly as
      indicated by plasma C-reactive protein (CRP) and AM levels. Thirty-seven subjects
      with dementia were selected from a community-dwelling, genetically isolated,
      geriatric population (above 60 years of age) based on the Mini Mental State
      Examination scale (MMSE) and the Diagnostic and Statistical Manual (DSM-IV)
      criteria. In parallel, a group of 33 age-matched healthy controls were selected
      from the same population. The levels of CRP (mg/l), sICAM-1 (ng/ml) and sVCAM-1
      (ng/ml) were measured in the serum samples of both groups. Serum concentrations
      of all three molecules sICAM-1, sVCAM-1 and CRP were significantly higher in the
      dementia group when compared to controls (656.78 +/- 161.51 versus 467.05 +/-
      231.26, p < 0.01; 631.64 +/- 149.76 versus 449.04 +/- 285.27, p < 0.01; 1.53 +/-
      0.97 versus 0.7221 +/- 0.61, p < 0.01, respectively). Furthermore, a positive
      correlation was observed between the three molecules studied and the degree of
      severity of cognitive impairment. The findings of this study enhance the
      hypothesis of the presence of an underlying inflammatory process leading to
      cognitive deterioration and predisposing dementia in the elderly. The present
      work supports the evaluation of inflammatory molecules as early indicators of
      cognitive decline in elderly individuals.

PMID- 16426757
TI  - Is CRPS I a neuropathic pain syndrome?

PMID- 16426758
TI  - Peripheral burning cold pain.

PMID- 16426759
TI  - Genetic impairment of interleukin-1 signaling attenuates neuropathic pain,
      autotomy, and spontaneous ectopic neuronal activity, following nerve injury in
      mice.
AB  - Peripheral nerve injury may lead to neuropathic pain, which is often associated
      with mechanical and thermal allodynia, ectopic discharge of from injured nerves
      and from the dorsal root ganglion neurons, and elevated levels of proinflammatory
      cytokines, particularly interleukin-1 (IL-1). In the present study, we tested the
      role of IL-1 in neuropathic pain models using two mouse strains impaired in IL-1
      signaling: Deletion of the IL-1 receptor type I (IL-1rKO) and transgenic over
      expression of the IL-1 receptor antagonist (IL-1raTG). Neuropathy was induced by
      cutting the L5 spinal nerve on one side, following which mechanical and thermal
      pain sensitivity was measured. Wild-type (WT) mice and the parent strains
      developed significant allodynia and hyperalgesia in the hind-paw ipsilateral to
      the injury compared with the contralateral hind-paw. The mutant strains, however,
      did not display decreased pain threshold in either hind-paw. Pain behavior was
      also assessed by cutting the sciatic and saphenous nerves and measuring autotomy
      scores. WT mice developed progressive autotomy, beginning at 7 days post-injury,
      whereas the mutant strains displayed delayed onset of autotomy and markedly
      reduced severity of the autotomy score. Electrophysiological assessment revealed
      that in WT mice a significant proportion of the dorsal root axons exhibited
      spontaneous ectopic activity at 1, 3, and 7 days following spinal nerve injury,
      whereas in IL-1rKO and IL-1raTG mice only a minimal number of axons exhibited
      such activity. Taken together, these results suggest that IL-1 signaling plays an
      important role in neuropathic pain and in the altered neuronal activity that
      underlies its development.

PMID- 16426760
TI  - Clinical prediction rules for the prognosis of shoulder pain in general practice.
AB  - Shoulder pain is common in primary care and has an unfavourable outcome in many
      patients. Information about predictors of outcome is scarce and inconsistent. The
      objective of this study was to develop clinical prediction rules for calculating
      the absolute risk of persistent shoulder symptoms for individual patients, 6
      weeks and 6 month after the first consultation in general practice. A prospective
      cohort study with 6 months follow-up was carried out in three geographic areas in
      The Netherlands. In this study, 587 patients with a new episode of shoulder pain
      were included. The main outcome measure was persistent symptoms at 6 weeks and 6
      months, perceived by the patient. Potential predictors included the results of a
      physical examination, sociodemographic variables, disease characteristics
      (duration of symptoms, pain intensity, disability and comorbidity), physical
      activity, physical workload and psychosocial factors. Response rates to the
      follow-up questionnaires were 83% at 6 weeks and 92% at 6 months. A longer
      duration of symptoms, gradual onset of pain and high pain severity at
      presentation were consistently associated with persistent symptoms at 6 weeks and
      6 months. The discriminative validity of our prediction rules was satisfactory
      with area under the curves of 0.74 (95% CI 0.70, 0.79) at 6 weeks and 0.67 (95%
      CI 0.63, 0.71) at 6 months. The performance of our rules needs to be tested in
      other populations of patients with shoulder pain to enable valid and reliable use
      of the rules in everyday clinical practice.

PMID- 16426761
TI  - A small scale survey of ivermectin resistance in sheep nematodes using the faecal
      egg count reduction test on samples collected from Scottish sheep.
AB  - Thirty-eight sheep flocks, predominantly from the south/central Scotland, were
      examined using a faecal egg count reduction test (FECRT) for the presence of
      ivermectin (IVM) resistant nematodes. Efficacies of less than 95%, 14-17 days
      post-treatment, were identified in 6 of 17 naturally grazing flocks where pre
      treatment faecal egg counts were in excess of 150 eggs per gram. Efficacies on
      these IVM resistant farms ranged from 66 to 92%. One other suspected cases of IVM
      resistance was also identified in returned material. The larvae detected in post
      treatment coprocultures from resistant flocks were from the genera Teladorsagia
      (4 from 6) and Trichostrongylus (2 from 6).

PMID- 16426762
TI  - Pituitary adenylate cyclase activating polypeptide reduces expression of Kv1.4
      and Kv4.2 subunits underlying A-type K(+) current in adult mouse olfactory
      neuroepithelia.
AB  - A-type K(+) currents (I(A)) in olfactory receptor neurons have been characterized
      electrophysiologically but the molecular identities of the underlying channel
      subunits have not been determined. Using RT-PCR, immunoblot and
      immunohistochemistry, we found that the two candidate channel families underlying
      I(A), shaker and shal, are expressed in olfactory epithelia of Swiss Webster
      mice. Specifically, Kv1.4, the only I(A) candidate from the shaker family, and
      Kv4.2 and Kv4.3 from the shal family were expressed, but Kv4.1 mRNA was not
      amplified from the olfactory epithelia. Immunoblot and immunohistochemical
      studies confirmed the existence of Kv1.4 and Kv4.2/3 subunits. Furthermore,
      quantitative RT-PCR showed that pituitary adenylate cyclase activating
      polypeptide (PACAP) reduced the expression of Kv1.4 and Kv4.2 but did not reduce
      the already low expression of Kv4.3. The PACAP-induced reduction of Kv4.1 and
      Kv4.2 expression was completely blocked by inhibiting the phospholipase C (PLC)
      pathway but was still significantly downregulated by PACAP when the cyclic AMP
      pathway was inhibited. In addition, downstream of the PLC pathway, calcium
      mediated the reduction of both Kv1.4 and Kv4.2 expression and I(A) current
      density. Phosphokinase C (PKC) activation did not affect Kv1.4 and Kv4.2 mRNA
      expression, even though PKC reduced I(A) current density. Together with our
      previous studies, our data suggest that A-type K(+) currents in olfactory
      receptor neurons are composed of multiple K(+) channel subunits, among which
      Kv1.4 and Kv4.2 are subject to transcriptional modulation by PACAP. We also found
      that PACAP predominately uses a PLC-calcium pathway to modulate Kv4.1 and Kv4.2
      expression. Modulation of A-type K(+) current expression may contribute to the
      previously observed neuroprotective effects of PACAP on olfactory receptor
      neurons.

PMID- 16426763
TI  - Aromatase expression in the human temporal cortex.
AB  - The expression of the human cyp19 gene, encoding P450 aromatase, the key enzyme
      for estrogen biosynthesis, involves alternative splicing of multiple forms of
      exon I regulated by different promoters. Aromatase expression has been detected
      in the human cerebral cortex, although the precise cellular distribution and
      promoter regulation are not fully characterized. We examined the variants of exon
      I of cyp19 by PCR analysis and the cellular distribution of the enzyme using
      immunohistochemistry in the human temporal cortex. We detected four different
      variants of exon I, suggesting a complex regulation of cyp19 in the cerebral
      cortex. In addition, the enzyme was localized mainly in a large subpopulation of
      pyramidal neurons and in a subpopulation of astrocytes. However, the majority of
      GABAergic interneurons identified by their expression of the calcium-binding
      proteins calbindin, calretinin and parvalbumin, did not display aromatase
      immunoreactivity. The broad range of potential modulators of the cyp19 gene in
      the cortex and the widespread expression of the protein in specific neuronal and
      glial subpopulations suggest that local estrogen formation may play an important
      role in human cortical function.

PMID- 16426764
TI  - Behavioral, central monoaminergic and hypothalamo-pituitary-adrenal axis
      correlates of fear-conditioned analgesia in rats.
AB  - Fear-conditioned analgesia is an important survival response which is expressed
      upon re-exposure to a context previously paired with a noxious stimulus. The aim
      of the present study was to characterize further the behavioral, monoaminergic
      and hypothalamo-pituitary-adrenal axis alterations associated with expression of
      fear-conditioned analgesia. Rats which had received footshock conditioning 24 h
      earlier, exhibited reduced formalin-evoked nociceptive behavior upon re-exposure
      to the footshock chamber, compared with non-footshocked formalin-treated rats.
      Intra-plantar injection of formalin reduced the duration of contextually-induced
      freezing and 20-40 kHz ultrasound emission. Intra-plantar injection of formalin
      to non-footshocked, non-conditioned rats did not induce ultrasonic vocalizations.
      Intra-plantar injection of formalin to footshock-conditioned rats, significantly
      increased tissue levels of 3,4-dihydroxyphenylacetic acid and the 3,4
      dihydroxyphenylacetic acid:dopamine ratio in the periaqueductal gray and reduced
      levels of dopamine in the thalamus, compared with saline-treated footshocked
      controls. Non-footshocked, non-conditioned rats were capable of mounting a robust
      formalin-evoked increase in plasma corticosterone levels. Moreover, plasma
      corticosterone levels were significantly higher in saline-treated, footshock
      conditioned rats compared with saline-treated non-footshocked rats and levels did
      not differ between saline- and formalin-treated footshock conditioned rats.
      Assessment of the effects of the intra-plantar injection procedure revealed an
      attenuation of short-term extinction of contextually-induced freezing in rats
      anesthetized for intra-plantar injection of saline compared with non
      anesthetized, non-injected rats as well as discrete effects on monoamines, their
      metabolites and plasma corticosterone levels. These data extend behavioral
      characterization of the phenomenon of fear-conditioned analgesia and suggest that
      measurement of ultrasound emission may be used as an ethologically relevant index
      of the defense response during fear-conditioned analgesia. Ultrasonic
      vocalization may also be a useful behavioral output to aid separation of
      nociception and aversion. The data provide evidence for discrete alterations in
      dopaminergic activity in the periaqueductal gray and thalamus and for altered
      hypothalamo-pituitary-adrenal axis activity following expression of defensive
      behavior.

PMID- 16426765
TI  - Subcortical deafferentation impairs behavioral reinforcement of long-term
      potentiation in the dentate gyrus of freely moving rats.
AB  - Long-term potentiation is a form of neural functional plasticity which has been
      related with memory formation and recovery of function after brain injury.
      Previous studies have shown that a transient early-long-term potentiation can be
      prolonged by direct stimulation of distinct brain areas, or behavioral stimuli
      with a high motivational content. The basolateral amygdala and other subcortical
      structures, like the medial septum and the locus coeruleus, are involved in
      mediating the reinforcing effect. We have previously shown that the lesion of the
      fimbria-fornix--the main entrance of subcortical afferents to the hippocampus-
      abolishes the reinforcing basolateral amygdala-effects on long-term potentiation
      in the dentate gyrus in vivo. It remains to be investigated, however, if such
      subcortical afferents may also be important for behavioral reinforcement of long
      term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria
      fornix-transected under anesthesia, and electrodes were implanted at the dentate
      gyrus and the perforant path. One week after surgery the freely moving animals
      were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop
      long-term potentiation when a short pulse duration was used for tetanization (0.1
      ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration
      to 0.2 ms per half-wave during tetanization resulted in a transient early-long
      term potentiation lasting about 4 h in the lesioned animals, comparable to that
      obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h)
      control animals, i.e. in non-lesioned and sham-operated rats, early-long-term
      potentiation could be behaviorally reinforced by drinking 15 min after
      tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation
      reinforcement by drinking was not detected. This result indicates that the effect
      of behavioral-motivational stimuli to reinforce long-term potentiation is
      mediated by subcortical, heterosynaptic afferents.

PMID- 16426766
TI  - Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and
      increased responses of spinal dorsal horn neurons to peripheral afferent
      stimulation.
AB  - Glutamate is a primary excitatory neurotransmitter in the mammalian CNS.
      Glutamate released from presynaptic neurons is cleared from the synaptic cleft
      passively by diffusion and actively by glutamate transporters. In this study, the
      role of glutamate transporters in sensory processing in the spinal cord has been
      investigated in behavioral, in vivo and in vitro experiments. Intrathecal
      application of a non-selective glutamate transport inhibitor, L-trans-pyrrolidine
      2,4-dicarboxylic acid (10 microl of 100 microM solution) induced hypersensitivity
      to peripheral mechanical and thermal stimuli. Topical application of L-trans
      pyrrolidine-2,4-dicarboxylic acid (100 microM) onto the dorsal surface of the L3
      L6 spinal cord increased spontaneous activities, innocuous and noxious stimulus
      evoked responses and after-discharges of wide dynamic range neurons in the L4-5
      spinal segments. Whole cell recordings made from superficial dorsal horn neurons
      in an isolated whole spinal cord from newborn rats (2-3 weeks old) revealed that
      bath-applied L-trans-pyrrolidine-2,4-dicarboxylic acid (100 microM) produced
      partial membrane depolarization, increased spontaneous action potentials with
      decreased neuronal membrane resistance and time constant, but without significant
      changes of capacitance. Finally, the amplitude and duration of primary afferent
      evoked-excitatory postsynaptic currents recorded from neurons in the substantia
      gelatinosa in the spinal slices from young adult rats (6-8 weeks old) were
      increased in the presence of L-trans-pyrrolidine-2,4-dicarboxylic acid (100
      microM). This study indicates that glutamate transporters regulate baseline
      excitability and responses of dorsal horn neurons to peripheral stimulation, and
      suggests that dysfunction of glutamate transporters may contribute to certain
      types of pathological pain.

PMID- 16426768
TI  - Neurofilament proteins are preferentially expressed in descending output neurons
      of the cat the superior colliculus: a study using SMI-32.
AB  - Physiological studies indicate that the output neurons in the multisensory (i.e.
      intermediate and deep) laminae of the cat superior colliculus receive converging
      information from widespread regions of the neuraxis, integrate this information,
      and then relay the product to regions of the brainstem involved in the control of
      head and eye movements. Yet, an understanding of the neuroanatomy of these
      converging afferents has been hampered because many terminals contact distal
      dendrites that are difficult to label with the neurochemical markers generally
      used to visualize superior colliculus output neurons. Here we show that the SMI
      32 antibody, directed at the non-phosphorylated epitopes of high molecular weight
      neurofilament proteins, is an effective marker for these superior colliculus
      output neurons. It is also one that can label their distal dendrites. Superior
      colliculus sections processed for SMI-32 revealed numerous labeled neurons with
      varying morphologies within the deep laminae. In contrast, few labeled neurons
      were observed in the superficial laminae. Neurons with large somata in the
      lateral aspects of the deep superior colliculus were particularly well labeled,
      and many of their secondary and tertiary dendrites were clearly visible.
      Injections of the fluorescent biotinylated dextran amine into the pontine
      reticular formation revealed that approximately 80% of the SMI-32 immunostained
      neurons also contained retrogradely transported biotinylated dextran amine,
      indicating that SMI-32 is a common cytoskeletal component expressed in descending
      output neurons. Superior colliculus output neurons also are known to express the
      calcium-binding protein parvalbumin, and many SMI-32 immunostained neurons also
      proved to be parvalbumin immunostained. These studies suggest that SMI-32 can
      serve as a useful immunohistochemical marker for detailing the somatic and
      dendritic morphology of superior colliculus output neurons and for facilitating
      evaluations of their input/output relationships.

PMID- 16426767
TI  - Zinc-rich transient vertical modules in the rat retrosplenial cortex during
      postnatal development.
AB  - The rat retrosplenial cortex is part of a heavily interconnected limbic circuit,
      considered to have an important role in spatial memory. Interestingly, the
      granular retrosplenial cortex has an exceptionally distinct system of dendritic
      bundles, originating from callosally projecting pyramidal neurons in layer II.
      These can be detected as early as postnatal day 5; and, although their functional
      significance remains to be elucidated, the existence of these bundles makes the
      granular retrosplenial cortex an attractive model system for a wide range of
      development and functional investigations. Here, we report four results
      concerning the development of modularity in the granular retrosplenial cortex in
      rats as investigated by neurochemical markers associated to cortico-cortical and
      thalamo-cortical connections. Emphasis is placed on zinc, an activity-related
      substance associated with glutamatergic, non-thalamic terminations. 1) Zinc shows
      a transient strong expression during early postnatal development, but later than
      the appearance of the upper layer bundles (at postnatal day 5). By postnatal day
      11 to postnatal day 15 staining for zinc achieved its most complex pattern; such
      that layer I had an elaborate organization both in the tangential and radial
      dimensions. Three sublaminae were distinguished (layers Ia-c): a superficial,
      thin tier (Ia) with patchy, moderate staining which periodically intruded into
      the underlying layer Ib ("funnel" modules), a middle band of variable width and
      light staining (Ib), and a deep, thin band with heavy and patchy staining (Ic)
      which, at rostral levels, spread upward into layer Ib (as "dome-like" modules).
      2) At postnatal day 15, immunohistochemical methods showed that layers Ia, b zinc
      funnels were co-localized with glutamate receptor subunits 2/3, GABA receptor
      type A alpha1 subunit and the thalamo-cortical marker, vesicular glutamate
      transporter 2. Layer Ic and the zinc dome-like modules were co-labeled for the
      cortico-cortical marker, vesicular glutamate transporter 1 and calretinin. 3) The
      spatial coincidence between zinc funnels in layers Ia, b and vesicular glutamate
      transporter 2 was further investigated by electron microscopy, which demonstrated
      co-localization of zinc and vesicular glutamate transporter 2 in synaptic
      boutons. The unusual co-localization of zinc and thalamo-cortical terminations
      was confirmed by retrograde transport of zinc to neurones in the anterodorsal
      thalamic nucleus at postnatal day 9 and postnatal day 13, and can thus be
      considered a transient zinc expression in thalamo-cortical boutons. This was not
      observed at postnatal day 28 or later. 4) After postnatal day 18, zinc staining
      started to fade in all layers. Before postnatal day 21, the heavy staining for
      zinc in the domes had completely disappeared. Zinc staining in layer Ia and the
      funnels virtually disappeared after postnatal day 28. A transient expression of
      zinc is reported in at least one other cortical area (layer IV of barrel cortex
      from postnatal day 5 to postnatal day 14, maximal at postnatal days 9-11). We
      conclude that the transient expression of zinc can occur in both limbic and
      sensory areas, and that down-regulation of zinc in cortical modules might be
      related to synaptic plasticity and remodeling during development.

PMID- 16426769
TI  - Sex differences in the responses of spinal wide-dynamic range neurons to
      subcutaneous formalin and in the effects of different frequencies of conditioning
      electrical stimulation.
AB  - The purpose of this study was to investigate sex-related differences in
      nociception elicited by s.c. injection of different concentrations (1-5%) of
      formalin. S.c. formalin-induced biphasic (early and late phases) persistent
      nociception was assessed by extracellularly recording the spontaneous activities
      of single spinal dorsal horn wide-dynamic range neurons in anesthetized male and
      female rats. The nociceptive responses of the dorsal horn wide-dynamic range
      neurons following s.c. injection of 5%, but not 1% and 2.5%, formalin in female
      rats were significantly stronger than the responses obtained in male rats.
      However, these concentration-dependent differences with respect to different
      sexes existed only in the late, but not the early, phase of formalin-induced
      nociception in intact, not spinal rats. The 5% formalin-induced late phase
      nociception in male rats was significantly depressed by 15 min of repeated
      conditioning electrical stimulation at a frequency of 5 Hz as well as 50 Hz
      during and after the period of conditioning electrical stimulation (intensity: 1
      mA; pulse duration: 1 ms). In contrast, the inhibitory effect of 50 Hz
      conditioning electrical stimulation on the 5% formalin-elicited late phase
      response in female rats was markedly greater in magnitude and longer in duration
      than that of 5 Hz conditioning electrical stimulation. No significant depressive
      effects of 5 Hz conditioning electrical stimulation on formalin-induced
      nociception were found in female rats, indicating that the distinct effects of
      conditioning electrical stimulation at different frequencies are different in
      animals of opposite sexes. In conclusion, s.c. administration of different
      concentrations of formalin shows a distinct sex-related difference in its late
      tonic nociception of spinal nociceptive sensory neurons. Sex differences in
      formalin-induced tonic nociception are stimulus intensity dependent and related
      to the modulation from the supraspinal regions. S.c. formalin-induced late phase
      nociception in female rats is only sensitive to depression at a frequency of 50
      Hz, but not 5 Hz, of conditioning electrical stimulation. This suggests that the
      involvement of the central mechanisms in the antinociceptive effects of
      conditioning electrical stimulation may be different at various frequencies of
      stimulation.

PMID- 16426770
TI  - Transhemispheric functional reorganization of the motor cortex induced by the
      peripheral contralateral nerve transfer to the injured arm.
AB  - Peripheral nerve injury in a limb usually causes functional reorganization of the
      contralateral motor cortex. However, a dynamic process of the novel
      transhemispheric functional reorganization in the motor cortex was found in adult
      rats after transferring the seventh cervical nerve root from the contralateral
      healthy side to the injured limb. Initially the ipsilateral motor cortex
      activated the injured forepaw for 5 months after the operation. Then, both
      hemispheres of the cortex activated the injured forepaw, and finally the
      contralateral cortex exclusively controlled the injured forepaw. It is concluded
      an extensive functional shift occurred between two hemispheres based on neural
      plasticity in the CNS. The experimental results of the later lesions of the
      ipsilateral cortex suggest that maintaining transhemispheric functional
      reorganization does not depend on the corpus callosum, but depends on mechanisms
      involving central axonal sprouting. Possible mechanisms underlying the
      alternative changes in cortical functions were discussed in rats and in patients
      having similar operations.

PMID- 16426771
TI  - An affective and cognitive model of marijuana and alcohol problems.
AB  - This study examined a six-month prospective model of marijuana and alcohol
      problems among college students. Among marijuana users, there was an indirect
      positive association between use utility and Time 1 (T1) marijuana-related
      problems through T1 marijuana use, whereas there was a direct positive
      association between affect lability and T1 marijuana-related problems. A multi
      group analysis of alcohol problems compared models for users of alcohol and
      marijuana and users of alcohol only. For both groups, there was a direct positive
      association between T1 use utility and T2 alcohol consumption and an indirect
      association with T2 alcohol problems via alcohol consumption. Impulsivity was
      directly and positively associated with T1 alcohol problems among the alcohol
      only group. For the alcohol-only group, impulsivity moderated the association
      between T2 consumption and problems, making it stronger. Associations between
      affect lability and alcohol problems as well as alcohol consumption and problems
      were stronger in the alcohol and marijuana group. Results support differential
      pathways to substance-related problems, an indirect pathway, in which problems
      are an unintended consequence of goal-directed use activity, as well as direct
      and interactive pathways in which problems may be viewed as consequences of
      broader regulatory problems.

PMID- 16426772
TI  - Allele-specific silencing of Alzheimer's disease genes: the amyloid precursor
      protein genes with Swedish or London mutations.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in humans. A
      pathological hallmark in the brain of an AD patient is extracellular amyloid
      plaques formed by accumulated beta-amyloid protein (Abeta), a metabolic product
      of amyloid precursor protein (APP). Studies have revealed a strong genetic
      linkage in the early-onset familial form (<60 years old) of AD. For example, some
      mutant APPs are transmitted dominantly and are segregated with inheritance of
      early onset AD. These mutants facilitate Abeta production. The "Swedish"
      mutations (APP(SW)) and the "London" mutation (APP(LON)) are examples of these
      mutants. Selective silencing of these mutant alleles holds therapeutic promise
      for AD. Here we show that the expression of the mutant APPs was selectively
      inhibited by RNA interference. The best selectivity was obtained when the
      mismatches were centrally placed in the antisense strand of small interfering
      RNAs. Introducing an additional mismatch in the antisense strand may improve the
      selectivity. The addition of a G at 5' end of the antisense strand may enhance
      the efficacy of gene silencing by RNA interference. Our results illustrate the
      guiding principles for selection of targeted sequences to achieve allele-specific
      silencing. The sequences that are effective to silence APP(SW) and APP(LON) as
      identified in this study may be useful in both in vivo and in vitro studies to
      investigate the pathophysiological role of APP(SW) and APP(LON) in AD
      development.

PMID- 16426773
TI  - Comparative immunogenicity of M. hyopneumoniae NrdF encoded in different
      expression systems delivered orally via attenuated S. typhimurium aroA in mice.
AB  - The Mycoplasma hyopneumoniae ribonucleotide reductase R2 subunit (NrdF) gene
      fragment was cloned into eukaryotic and prokaryotic expression vectors and its
      immunogenicity evaluated in mice immunized orally with attenuated Salmonella
      typhimurium aroA CS332 harboring either of the recombinant expression plasmids.
      We found that NrdF is highly conserved among M. hyopneumoniae strains. The
      immunogenicity of NrdF was examined by analyzing antibody responses in sera and
      lung washes, and the cell-mediated immune (CMI) response was assessed by
      determining the INF-gamma level produced by splenocytes upon in vitro stimulation
      with NrdF antigen. S. typhimurium expressing NrdF encoded by the prokaryotic
      expression plasmid (pTrcNrdF) failed to elicit an NrdF-specific serum or
      secretory antibody response, and IFN-gamma was not produced. Similarly, S.
      typhimurium carrying the eukaryotic recombinant plasmid encoding NrdF (pcNrdF)
      did not induce a serum or secretory antibody response, but did elicit significant
      NrdF-specific IFN-gamma production, indicating induction of a CMI response.
      However, analysis of immune responses against the live vector S. typhimurium aroA
      CS332 showed a serum IgG response but no mucosal IgA response in spite of its
      efficient invasiveness in vitro. In the present study we show that the DNA
      vaccine encoding the M. hyopneumoniae antigen delivered orally via a live
      attenuated S. typhimurium aroA can induce a cell-mediated immune response. We
      also indicate that different live bacterial vaccine carriers may have an
      influence on the type of the immune response induced.

PMID- 16426774
TI  - Tumor promoting potency of PCBs 28 and 101 in rat liver.
AB  - Only few data are available on the carcinogenic potency of individual PCB
      congeners. In this study, we tested the 'non-dioxinlike' congeners PCB 28 and 101
      for their potency as liver tumor promoters in female rats which received diethyl
      N-nitrosamine as an initiator. After 8 or 16 weeks of PCB treatment (50 and 150
      micromol/kg body weight per week), each congener was recovered in the liver
      according to the dose levels applied, with PCB 28, at the same dose level,
      showing nine- to 16-fold higher hepatic levels than PCB 101 (approximately, 44
      micromol/kg versus 5 micromol/kg liver at low dose, 145 micromol/kg versus 9
      micromol/kg liver at high dose). PCB 28 was found to mildly induce hepatic EROD
      activity, while both congeners induced PROD activity. With each congener, no
      significant increase in the number of ATPase-deficient or GSTP-positive
      preneoplastic foci was obtained, while a significant increase in the relative
      hepatic volume of ATPase-deficient foci was found in the livers of DEN pre
      treated animals having received 50 micromol/kg body weight of PCB 101 per week
      over 16 weeks. Our results revealed that neither the accumulative PCB 28 nor the
      more readily metabolisable PCB 101 was an efficacious tumor promoter in the
      livers of female rats.

PMID- 16426775
TI  - Influence of repeated regrouping on reproduction in gilts.
AB  - It is generally assumed that stress around oestrus and during early pregnancy
      reduces reproductive performance of pigs. In our experiment, late prepuberal
      gilts (age at arrival 225+/-6 days) were housed in groups of four. Stress
      treatment consisted of once weekly regrouping and twice weekly feed competition
      of the 28 Stress gilts during 6 consecutive weeks, starting 13 days after
      arrival. Control gilts (n=28) were not treated. During the 0.5-1.5h after
      regroupings, Stress animals fought consistently more than the Control animals; up
      to 13 of the Stress animals fought for at most 60% of the time compared to one
      Control animal fighting for at most 3.3% of the time. The day before first
      regrouping, gilts had on average 4.0+/-0.9 skin scratches. By week 6, this number
      had reduced to 2.1+/-1.0 in Control, but remained 4.0+/-1.3 in Stress gilts
      (P<0.05). In the afternoon after regroupings, skin scratches increased up to
      6.3+/-1.6 in the Stress gilts. Saliva cortisol in the afternoon before regrouping
      did not differ between weeks 1, 3 and 6, nor did it differ between Stress and
      Control. In Stress gilts, saliva cortisol was increased in the afternoon of first
      regrouping, in Batch 2 only (from 1.8+/-0.4 to 4.1+/-0.9 ng/ml; P<0.05). Animals
      showing a second oestrus within 5 weeks after arrival were inseminated. Duration
      of second oestrus of these animals was 2.48+/-0.66 days in the Stress gilts
      (n=24) and 2.21+/-0.58 days in the Control gilts (n=22; P>0.10). At Day 35 after
      insemination, pregnancy rate was 100% in both groups. Ovulation rate and number
      of total and vital fetuses was similar (P>0.10). The Stress treatment during a 6
      week period around insemination consistently resulted in fighting but did not
      result in long term effects on cortisol levels and did not impair reproductive
      performance.

PMID- 16426777
TI  - Release characteristics of anionic drug compounds from liquid crystalline gels.
      Part II. The effects of ion pairing and buffering on the passive delivery of
      anionic drugs across non-rate-limiting membranes.
AB  - This is the second in a series of papers that report on the release and transport
      of a range of anionic drugs (diclofenac, salicylic acid) from liquid crystalline
      gels and ultimately on their use in transdermal delivery. The previous paper
      [Fitzpatrick, D., Corish, J., 2005. Release characteristics of anionic drug
      compounds from liquid crystalline gels for transdermal delivery. Part I. Passive
      release across non-rate limiting membranes. Int. J. Pharm. 301, 226-236]
      investigated passive release profiles across a non-rate-limiting membrane: here
      we report on the search for a suitable model enhancer (benzyl dimethyldodecyl
      ammonium bromide) for the transdermal delivery of anionic compounds. The results
      presented reveal a significant role for ion pairing and for buffering, analogous
      to those found in the investigations of cationic species (salbutamol) by Nolan,
      L.M.A., Corish, J., Corrigan, O.I., Fitzpatrick, D., 2003. Iontophoretic and
      chemical enhancement of drug delivery. Part I. Across artificial membranes. Int.
      J. Pharm. 12, 41-55. The method of vehicle preparation is also investigated. It
      is shown that ion pairing of the drug with the enhancer decreases the amount of
      drug available for transport from the liquid crystalline gels into aqueous
      receptor media. This decrease is directly related to the ratio of the
      concentration of drug to that of the enhancer. Buffering the vehicle inhibits the
      ion-pair formation to some extent. Vehicle preparation was also found to
      influence the degree of ion-pair association. The inclusion of a similarly
      charged enhancer (oleic acid) to the drug was found not to impede the diffusion
      of the drug from the gels.

PMID- 16426776
TI  - Effect of alterations in the quantity and composition of the pre-mating diet on
      embryo survival and foetal growth in the pig.
AB  - This trial examined the effects of feeding six diets, which varied in either
      amount or composition, during the oestrous cycle prior to insemination on embryo
      survival and foetal development on day 27+/-2 of pregnancy in gilts. Ten or 11
      gilts per group received either a maintenance (M) diet, 1.8 x M, 2.6 x M or
      nutritionally balanced diets in which the content of fibre, protein or starch was
      increased. Of the six diets tested, only the high fibre diet significantly
      increased embryo survival when compared to its 1.8 x M isoenergetic control
      (88.20+/-1.96% versus 81.25+/-2.67%; P<0.05). More litters from gilts fed the 1.8
      x M and the starch diets had foetuses defined as intra-uterine growth retarded
      (IUGR; 50% and 62.5 of litters, respectively), compared to the other four groups
      in which 0-12.5% of litters contained IUGR foetuses (P<0.05). There was no effect
      of dietary treatment on foetal or placental size or on the within-litter
      variability in foetal and placental size. Plasma concentrations of oestradiol and
      progesterone on days 4-8 of the oestrous cycle and on day 27+/-2 of pregnancy
      were unaffected by treatment. Feed intake was positively related to mean plasma
      IGF-1 concentrations on days 4-8 of the cycle (P<0.01) and to mean leptin
      concentrations on days 4 and 5 (P<0.001). Leptin concentrations were unaffected
      by alterations in the composition of the diet, whereas IGF-1 concentrations were
      higher in gilts fed the starch diet compared to the M control (159+/-9.52 versus
      127+/-7.65 ng/ml; P<0.05). These data demonstrate that alteration to the
      composition of the feed consumed during the cycle before insemination can affect
      both embryo survival and the distribution of foetal size within the litter. The
      underlying mechanism(s) remain to be determined, but probably involve dietary
      induced changes in concentrations of reproductive hormones and/or intermediary
      metabolites that in turn affect ovarian follicular and oocyte development.

PMID- 16426779
TI  - Influence of particle size on transport of methotrexate across blood brain
      barrier by polysorbate 80-coated polybutylcyanoacrylate nanoparticles.
AB  - Transports of methotrexate-loaded polybutylcyanoacrylate nanoparticles with
      different sizes across blood brain barrier were investigated in this experiment.
      The drug-loaded nanoparticles were prepared by emulsion polymerization method.
      After coating with polysorbate 80, nanoparticles with the size 70, 170, 220, 345
      nm were, respectively, i.v. injected into rats at the dose of 3.2 mg/kg. Uncoated
      nanoparticles and methotrexate solution were also i.v. injected at the same
      dosage as controls. 0.5, 1, 1.5, 2, 3, 4 h after injection, cerebrospinal fluids
      and brain tissues were collected for tests. Drug level in all biological samples
      was determined by HPLC. It was found out that nanoparticles overcoated by
      polysorbate 80 could significantly improve the drug level in both brain tissues
      and cerebrospinal fluids compared with uncoated ones and simple solution. Seventy
      nanometer nanoparticles could deliver more drugs into brain while no significant
      difference was observed among the other three size ranges. In conclusion,
      polysorbate 80-coated polybutylcyanoacrylate nanoparticles could be used to
      overcome blood brain barrier especially those whose diameter was below 100 nm.

PMID- 16426778
TI  - Elimination of metformin-croscarmellose sodium interaction by competition.
AB  - During analytical method development and validation, a strong charge interaction
      between metformin and croscarmellose sodium was observed when the aqueous
      solution containing metformin was spiked with croscarmellose sodium. The charge
      interaction resulted in the retention of metformin in croscarmellose sodium and
      caused a serious drug recovery problem. The percent recovery of metformin in the
      solution was much lower than its theoretical values, especially in the low
      metformin concentration range. To overcome the metformin-croscarmellose
      interaction, arginine was selected as a competitor for the binding sites on
      croscarmellose sodium. Because of the competition and stronger interaction
      between arginine and croscarmellose sodium than metformin and croscarmellose
      sodium, a complete recovery of metformin in presence of arginine in both low and
      high concentration ranges was achieved. The effect of arginine on the recovery of
      metformin and the competition mechanism are discussed in this paper.

PMID- 16426780
TI  - Mapping quantitative trait loci for hearing loss in Black Swiss mice.
AB  - In common inbred mouse strains, hearing loss is a highly prevalent quantitative
      trait, which is mainly controlled by the Cdh23(753A) variant and alleles at
      numerous other strain-specific loci. Here, we investigated the genetic basis of
      hearing loss in non-inbred strains. Mice of Swiss Webster, CF-1, NIH Swiss, ICR,
      and Black Swiss strains exhibited hearing profiles characteristic of progressive,
      sensorineural hearing impairment. In particular, CF-1, Black Swiss, and NIH Swiss
      mice showed early-onset hearing impairment, ICR and Swiss Webster mice expressed
      a delayed-onset hearing loss, and NMRI mice had normal hearing. By quantitative
      trait locus (QTL) mapping, two significant QTLs were identified underlying
      hearing loss in Black Swiss mice: one QTL mapped to chromosome (chr) 10 (named
      ahl5, LOD 8.9, peak association 35-42 cM) and a second QTL localized to chr 18
      (ahl6, LOD 3.8, 38-44 cM). Ahl5 and ahl6 account for 61% and 32% of the variation
      in the backcross, respectively. Cadherin 23 (Cdh23) and protocadherin 15
      (Pcdh15), mapping within the 95% confidence interval of ahl5, bear nucleotide
      polymorphisms in coding exons, but these appear to be unrelated to the hearing
      phenotype. Haplotype analyses across the Cdh23 locus demonstrated the
      phylogenetic relationship between Black Swiss and common inbred strains.

PMID- 16426781
TI  - Slow motility in hair cells of the frog amphibian papilla: Ca2+-dependent shape
      changes.
AB  - We investigated the process of slow motility in non-mammalian auditory hair cells
      by recording the time course of shape change in hair cells of the frog amphibian
      papilla. The tall hair cells in the rostral segment of this organ, reported to be
      the sole recipients of efferent innervation, were found to shorten in response to
      an increase in the concentration of the intracellular free calcium. These
      shortenings are composed of two partially-overlapping phases: an initial rapid
      iso-volumetric contraction, followed by a slower length decrease accompanied with
      swelling. It is possible to unmask the iso-volumetric contraction by delaying the
      cell swelling with the help of K+ or Cl- channel inhibitors, quinine or
      furosemide. Furthermore, it appears that the longitudinal contraction in these
      cells is Ca2+-calmodulin-dependent: in the presence of W-7, a calmodulin
      inhibitor, only a slow, swelling phase could be observed. These findings suggest
      that amphibian rostral AP hair cells resemble their mammalian counterparts in
      expressing both a Ca2+-calmodulin-dependent contractile structure and an
      "osmotic" mechanism capable of mediating length change in response to
      extracellular stimuli. Such a mechanism might be utilized by the efferent
      neurotransmitters for adaptive modulation of mechano-electrical transduction,
      sensitivity enhancement, frequency selectivity, and protection against over
      stimulation.

PMID- 16426782
TI  - Daboia russellii and Naja kaouthia venom neutralization by lupeol acetate
      isolated from the root extract of Indian sarsaparilla Hemidesmus indicus R.Br.
AB  - The present study reports the isolation and purification of lupeol acetate from
      the methanolic root extract of Indian medicinal plant Hemidesmus indicus (L.)
      R.Br. (family: Asclepiadaceae) which could neutralize venom induced action of
      Daboia russellii and Naja kaouthia on experimental animals. Lupeol acetate could
      significantly neutralize lethality, haemorrhage, defibrinogenation, edema, PLA(2)
      activity induced by Daboia russellii venom. It also neutralized Naja kaouthia
      venom induced lethality, cardiotoxicity, neurotoxicity and respiratory changes in
      experimental animals. Lupeol acetate potentiated the protection by snake venom
      antiserum action against Daboia russellii venom induced lethality in male albino
      mice. Venom induced changes in lipid peroxidation and super oxide dismutase
      activity was antagonized by lupeol acetate. Snake venom neutralization by lupeol
      acetate and its possible mechanism of action has been discussed.

PMID- 16426786
TI  - Pathological demonstration of rapid involvement into the subcutaneous tissue in a
      case of fatal hydrofluoric acid burns.
AB  - We report an autopsy case of a man who suffered accidental chemical burns
      following exposure to 60% hydrofluoric acid. The extent of the burns covered
      about 30% of his body surface, and cardiopulmonary arrest occurred about 30min
      after the exposure. At autopsy, the skin of the affected area showed greenish
      gray or black coloring with thin circumferential erythema, and this discoloration
      extended as far as the periosteum of the skull. However, such discoloration was
      not found on the mucosa of the airway or the gastrointestinal tract.
      Microscopically, severe liquefactive necrosis was already evident on the skin.
      Elastic fibers within the dermis were completely lost, and the entire wall of
      large vessels within the subcutaneous layer was already severely affected. Blood
      analysis in the emergency room showed hypocalcemia, and the levels of fluoride
      ions in the postmortem blood and urine showed extremely high values. However,
      fewer fluoride ions were detected from the lung tissue. The present case suggests
      that the hydrofluoric acid had immediately penetrated down into the deep layer of
      the skin, thereby involving the large vessels present within the subcutaneous
      layer. These pathological findings of the skin seen in the present case explain
      the mechanism behind the rapid dissemination of fluoride ions which entered the
      bloodstream from damaged arteries, resulting in the development of acute
      toxicity.

PMID- 16426785
TI  - Allele frequencies for 15 autosomal STR loci and admixture estimates in Puerto
      Rican Americans.
AB  - Allelic frequencies of 15 short tandem repeats (STR) markers (CSF1PO, FGA, THO1,
      TPOX, VWA, D3S11358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11,
      D19S433 and D2S1338) were determined using the AmpFl STR Identifiler PCR
      Amplification Kit in Puerto Rican American individuals (N=205) from
      Massachusetts. The FGA, D18S51 and D2S1338 loci had a high power of
      discrimination (PD) with values of 0.967, 0.965 and 0.961, respectively.
      Significant deviations from the Hardy-Weinberg (HW) equilibrium were not
      detected. An important genetic contribution of Caucasian European (76.4%) was
      detected in Puerto Rican Americans. However, comparative analysis between Puerto
      Rican American and other neighboring populations from United States mainly with
      African and Caucasian Americans, revealed significant differences in the
      distribution of STR markers. Our results are important for future comparative
      genetic studies of different American ethnic groups, in particular a cultural
      group called Hispanic-Americans and should be helpful for forensic and paternity
      testing.

PMID- 16426787
TI  - Adolescent homicides in Finland: offence and offender characteristics.
AB  - Approximately 9% of the homicides in Finland are committed by adolescents under
      20 years of age. The purpose of this study was to investigate the offence and
      offender characteristics in homicidal adolescents. Forensic psychiatric
      evaluation statements of adolescent offenders accused of a homicide during 1990
      2001 were reviewed retrospectively (n=57). In 38% of the cases, there were
      multiple offenders. In 58% of the cases, the victim was an acquaintance, in 25% a
      stranger, in 12% a family member and in 5% of the cases an (ex)intimate partner.
      Sixty-nine percent of the offenders were intoxicated and 21% under the influence
      of drugs at the time of the killing. The most frequent motives were an argument
      (25%) and a robbery (25%). Sixty-four percent of the offenders had developmental
      problems and 42% had a crime history. Approximately half were diagnosed as having
      a conduct or a personality disorder, but 32% of the offenders were considered not
      to suffer from a mental illness or substance abuse. For 63%, the level of
      intellectual functioning was average or above average. There were signs of more
      than one form of violence in 54% of the cases and 28% of the cases contained
      excessive violence. The use of multiple and excessive violence was significantly
      related to the offender age, multiple offenders, offender-victim relationship and
      substance abuse, but not related to having developmental problems, crime history
      or mental illness.

PMID- 16426788
TI  - An unusual case of thermal injuries with a hot glue gun. Deliberate self-harm or
      maltreatment?
AB  - Assessing injuries in forensic medicine casework, examiners are often confronted
      with the question of self-infliction versus third parties' influence,
      respectively, deliberate self-harm versus maltreatment. We report the case of a
      40-year-old male who presented with numerous partially healed thermal injuries of
      different age. These burns were shaped like capital letters and little circles,
      which were arranged in lines in a regular form. The lesions were found on the
      whole body with exclusion of face, genitals, hands and feet. Furthermore, four
      bitemarks at the right shoulder were noted. Investigations revealed that the man
      had been abused by his 25-year-old wife (presumably a borderline personality
      disorder patient) for at least 1 year. In addition to another series of abuses,
      the woman may have inflicted the shaped burns with a hot glue gun as punishment
      for breaking certain "rules" she had established. When assessing injuries of
      patients in forensic medicine, several considerations regarding etiology have to
      be taken into account. In principle, the victim's testimony, the anamnesis, the
      police investigation results and the findings from the forensic physical
      examination have to be balanced against each other. The injury pattern in the
      present case showed contradictory single characteristics both of deliberate self
      harm and of maltreatment. After forensic analysis, it was assessed as injuries
      inflicted by an assistant with the patient's consent.

PMID- 16426789
TI  - Contrast-enhanced coronary artery visualization by dual-source computed
      tomography--initial experience.
AB  - Multi-detector computed tomography (CT) scanners, by virtue of their high
      temporal and spatial resolution, permit imaging of the coronary arteries.
      However, motion artifacts, especially in patients with higher heart rates, can
      impair image quality. We thus evaluated the performance of a new dual-source CT
      (DSCT) with a heart rate independent temporal resolution of 83 ms for the
      visualization of the coronary arteries in 14 consecutive patients. METHODS:
      Fourteen patients (mean age 61 years, mean heart rate 71 min(-1)) were studied by
      DSCT. The system combines two arrays of an X-ray tube plus detector (64 slices)
      mounted on a single gantry at an angle of 90 degrees With a rotation speed of 330
      ms, a temporal resolution of 83 ms (one-quarter rotation) can be achieved
      independent of heart rate. For data acquisition, intraveous contrast agent was
      injected at a rate of 5 ml/s. Images were reconstructed with 0.75 slice thickness
      and 0.5 mm increment. The data sets were evaluated concerning visibility of the
      coronary arteries and occurrence of motion artifact. RESULTS: Visualization of
      the coronary arteries was successful in all patients. Most frequently, image
      reconstruction at 70% of the cardiac cycle provided for optimal image quality
      (50% of patients). Of a total of 226 coronary artery segments, 222 (98%) were
      visualized free of motion artifact. In summary, DSCT constitutes a promising new
      concept for cardiac CT. High and heart rate independent temporal resolution
      permits imaging of the coronary arteries without motion artifacts in a
      substantially increased number of patients as compared to earlier scanner
      generations. Larger and appropriately designed studies will need to determine the
      method's accuracy for detection of coronary artery stenoses.

PMID- 16426790
TI  - An optimized reverse-phase high performance liquid chromatographic method for
      evaluating percutaneous absorption of glucosamine hydrochloride.
AB  - A relatively simple, selective, precise and accurate high performance liquid
      chromatography (HPLC) method based on a reaction of phenylisothiocyanate (PITC)
      with glucosamine (GL) in alkaline media was developed and validated to determine
      glucosamine hydrochloride permeating through human skin in vitro. It is usually
      problematic to develop an accurate assay for chemicals traversing skin because
      the excellent barrier properties of the tissue ensure that only low amounts of
      the material pass through the membrane and skin components may leach out of the
      tissue to interfere with the analysis. In addition, in the case of glucosamine
      hydrochloride, chemical instability adds further complexity to assay development.
      The assay, utilising the PITC-GL reaction was refined by optimizing the reaction
      temperature, reaction time and PITC concentration. The reaction produces a
      phenylthiocarbamyl-glucosamine (PTC-GL) adduct which was separated on a reverse
      phase (RP) column packed with 5 microm ODS (C18) Hypersil particles using a diode
      array detector (DAD) at 245 nm. The mobile phase was methanol-water-glacial
      acetic acid (10:89.96:0.04 v/v/v, pH 3.5) delivered to the column at 1 ml min-1
      and the column temperature was maintained at 30 degrees C. Galactosamine
      hydrochloride (Gal-HCl) was used as an internal standard. Using a saturated
      aqueous solution of glucosamine hydrochloride, in vitro permeation studies were
      performed at 32+/-1 degrees C over 48 h using human epidermal membranes prepared
      by a heat separation method and mounted in Franz-type diffusion cells with a
      diffusional area 2.15+/-0.1 cm2. The optimum derivatisation reaction conditions
      for reaction temperature, reaction time and PITC concentration were found to be
      80 degrees C, 30 min and 1% v/v, respectively. PTC-Gal and GL adducts eluted at
      8.9 and 9.7 min, respectively. The detector response was found to be linear in
      the concentration range 0-1000 microg ml-1. The assay was robust with intra- and
      inter-day precisions (described as a percentage of relative standard deviation,
      %R.S.D.) <12. Intra- and inter-day accuracy (as a percentage of the relative
      error, %RE) was <or=-5.60 and <or=-8.00, respectively. Using this assay, it was
      found that GL-HCl permeates through human skin with a flux 1.497+/-0.42 microg cm
      2 h-1, a permeability coefficient of 5.66+/-1.6x10(-6) cm h-1 and with a lag time
      of 10.9+/-4.6 h.

PMID- 16426792
TI  - Conformational evaluation and detailed 1H and 13C NMR assignments of flavoxate, a
      urinary tract antispasmodic agent.
AB  - 1H and 13C NMR chemical shift assignments for the urinary tract antispasmodic
      flavoxate (1) and flavoxate hydrochloride (2) were obtained from one- and two
      dimensional measurements. A Monte Carlo random search using molecular mechanics,
      followed by geometry optimization of each minimum energy structure employing DFT
      calculations at the B3LYP/6-31G* level, and a Boltzmann analysis of the total
      energies, provided accurate molecular models which describe the conformational
      behavior of flavoxate (1). The electron density surfaces for the global minimum
      and the second minimum conformers 1a and 1b of this L-type Ca2+ channel inhibitor
      were calculated. The presence of both conformers in solution was demonstrated in
      full agreement with 2D NOESY data and NOE difference spectroscopy.

PMID- 16426791
TI  - Separation of fibrate-type antihyperlipidemic drugs by capillary electrophoresis
      and their quantitation in pharmaceuticals.
AB  - Six antihyperlipidemic agents-bezafibrate, ciprofibrate, clofibrate, clofibric
      acid, fenofibrate and gemfibrozil were separated by means of capillary
      electrophoresis, using unmodified fused silica tubing of 75 microm internal
      diameter and 87 cm length (65 cm to the UV detector at 227 nm). Migration time
      and selectivity were examined in differing pH of separation buffer, varying
      separation voltage and differing temperature. Optimal separation was achieved
      using 1/15 M phosphate buffer pH 10, 240 V/cm at 25 degrees C. The optimal
      separation conditions were then used to elaborate the method of quantitation of
      bezafibrate, ciprofibrate and gemfibrozil in Bezamidin, Lipanor and Gemfibral
      pharmaceuticals. The clofibric acid was used as internal standard. The
      calibration curve was constructed from 0.2 to 0.8 mg/ml of each compound and 0.5
      mg/ml of internal standard. The calibration data were proved to be linear by
      Mandel and Lack-of-fit tests. Statistical evaluation of results proved proper
      recovery of elaborated method (102.42, 97.32 and 101.51%, respectively) and good
      repeatability (9.51, 5.52 and 11.15%, respectively). The linearity of recovery
      was also tested by analyzing increasing amount of the samples. Three fortified
      samples of each drug were also analyzed to perform additional accuracy
      validation.

PMID- 16426793
TI  - Spectrum and potency of dalbavancin tested against 3322 Gram-positive cocci
      isolated in the United States Surveillance Program (2004).
AB  - Dalbavancin is an injectable, next generation lipoglycopeptide with an extended
      serum elimination half-life. Once-weekly dosing has been successful for treatment
      of skin and skin structure (SSSI) and catheter-related bloodstream infections (CR
      BSI). Concurrent with clinical trails, dalbavancin resistance surveillance was
      initiated in 2003, and results are reported here for the 2004 United States (USA)
      component. A total of 3322 Gram-positive cocci were tested by reference broth
      microdilution methods. Organism species tested included: Staphylococcus aureus
      (2102; 49% oxacillin-resistant), coagulase-negative staphylococci (CoNS; 255, 82%
      oxacillin-resistant), beta-hemolytic streptococci (241), viridans group
      streptococci (46), and Streptococcus pneumoniae (678). Dalbavancin (MIC90,0.06
      0.12 microg/mL) was comparable in spectrum, but superior in potency to vancomycin
      (MIC90,1-2 microg/mL) against staphylococci. Dalbavancin MIC90 values against the
      tested streptococci was 0.03 microg/mL. Dalbavancin was more active against
      tested SSTI pathogens than comparator agents having complete susceptibility rates
      (100.0%) similar to vancomycin. Vancomycin, (16- to 32-fold), linezolid (8- to 32
      fold), daptomycin (4- to 32-fold), and quinupristin/dalfopristin (4- to 32-fold)
      were less active than dalbavancin. In conclusion, dalbavancin exhibited greater
      potency than comparison glycopeptides or lipopeptides, streptogramin
      combinations, and oxazolidinones against Gram-positive pathogens associated with
      SSSI or CR-BSI. Dalbavancin wild-type MIC distributions remain unchanged compared
      with prior sampled years (2002-2003) in the USA.

PMID- 16426794
TI  - O1 and non-O1 Vibrio cholerae bacteremia produced by hemolytic strains.
AB  - Vibrio cholerae are Gram-negative bacteria capable of producing serious
      infections. They are differentiated into O1 and non-O1 serogroups, depending on
      their ability to agglutinate with specific antiserum. In contrast to non-O1 V.
      cholerae, which are more prone to invading the bloodstream, V. cholerae O1 is
      rarely the cause of bacteremia. We describe 2 cases of O and non-O1 V. cholerae
      bacteremia in patients with hepatitis C virus cirrhosis. We postulate that the
      hemolytic properties of the isolates contributed to their virulence in
      immunocompromised hosts.

PMID- 16426795
TI  - Early callosal absence disrupts the establishment of normal neocortical structure
      in Swiss mice.
AB  - In the present study, we tested the hypothesis that the ontogenetic development
      of the corpus callosum is relevant for the establishment of a normal neocortical
      structure. To that effect, neocortical morphology (thickness and neuronal
      density) was analyzed in adult Swiss mice rendered acallosal by midline
      transection at the first postnatal day (Acallosal group) and in non-manipulated
      mice. The neocortical thicknesses and neuronal densities of layers II+III through
      VI were measured in area 6 and at the 17/18a border, both of which present
      abundant callosal inputs, and in the relatively acallosal area 17. For the
      thickness measure, significant differences between Non-manipulated and Acallosal
      groups were only found in the areas that receive massive callosal connections. In
      area 6, Acallosal mice presented a reduced thickness of layer V, while at the
      17/18a border, these mice presented a reduced thickness of layers II+III when
      compared to non-manipulated ones. No statistical difference between acallosal and
      non-manipulated mice was found regarding the neuronal density measure. The
      reduced cortical thickness associated with a comparatively normal neuronal
      density in neocortical regions which normally have abundant callosal connections
      suggest a reduction in the number of cortical neurons in acallosal mice.
      Altogether, the present data indicate that the input provided by callosal axons
      is necessary for the normal development of the neocortex.

PMID- 16426796
TI  - Making communication research matter: what do patients notice, what do patients
      want, and what do patients need?
AB  - OBJECTIVE: To explore limitations of current communication theory by considering
      different perspectives of researchers, clinicians, patients and teachers of
      communication. METHOD: Theory development based on limitations of the current
      communication research literature due to inconsistencies between patient reports
      and observed communication behavior. RESULTS: While researchers focus on the
      mechanics and techniques of communication, patients seek relationships in which
      they experience trust, the right amount of autonomy, caring, and expertise.
      Patients', physicians', and communication experts' perspectives do not always
      define the same problems and often point to different solutions. CONCLUSIONS: In
      addition to studying clinician behaviors and patient perceptions of care,
      communication research should focus on five additional factors: what patients
      notice, want and need, and how their perspectives differ from those of physicians
      and researchers; the context, including illness severity and type and family
      influences; how complex health systems facilitate and impede communication;
      patients' influences on physician communication behavior; and habits of mind that
      promote attentive care.

PMID- 16426797
TI  - Patient information at discharge--a study of a combined approach.
AB  - OBJECTIVE: To describe patients' perceptions of a new information procedure
      related to going home after urological surgery. This procedure, developed in an
      action research project, included a discharge talk with the nurse and an
      information booklet for the patients to keep. METHODS: A convenience sample of 99
      patients responded to a survey sent home 1 week after discharge (return 78.6%).
      The Patient Information and Nurse Interaction Scale (PINI) was used for data
      collection. RESULTS: The sample were mostly male (81%), older (mean 71.9 years),
      and hospitalised on average less than 4 days. Patients who got the booklet had
      significantly more favourable perceptions on information received (p<0.05) on 11
      of 21 items, and 91% said they would not have managed very well at home without
      it. CONCLUSION: The patients who received the booklet knew more about what might
      happen to them, were less uncertain and had fewer concerns when going home.
      PRACTICE IMPLICATIONS: The combination of standardised written information and a
      talk with the nurse where patients participated in individualising the
      information appears to have had a significant impact on self-management at home.

PMID- 16426798
TI  - Evaluation of haptotherapy for patients with cancer treated with chemotherapy at
      a day clinic.
AB  - OBJECTIVE: The purpose of this study was to evaluate a haptotherapeutic treatment
      and its effects on the perceived well-being of patients with cancer treated with
      chemotherapy in day care. METHODS: The study had a pre-test-post-test semi
      experimental design, with 31 patients in the intervention group and 26 in the
      control group. Patients in the control group were matched with patients in the
      experimental condition with respect to age, gender, type of cancer, type of
      chemotherapy, prognosis and the period between pre- and post-test. Standardized
      questionnaires were used measuring perceived well-being and satisfaction with
      care (haptotherapy). Indicators of well-being measured were quality of life,
      mood, meaning in life, general functioning, physical and psychological symptoms,
      sleep quality and body awareness. The intervention consisted of five haptotherapy
      sessions of 45 minutes each. Patients in the control condition received standard
      medical care. RESULTS: Patients were highly satisfied with the haptotherapy
      treatment, and especially valued the personal attention and the relaxation they
      experienced. The haptotherapy treatment improved both the perceived general
      quality of life and the perceived cognitive and social functioning of patients.
      No improvement was found for mood, meaning in life, general functioning, physical
      symptoms, sleep quality and body awareness. CONCLUSION: It may be concluded that
      haptotherapy positively contributes to several indicators of perceived well-being
      of patients with cancer during the period they receive chemotherapy. More
      rigorous experimental studies are necessary in this field, especially concerning
      randomization, number of participants and homogeneity of the sample. PRACTICE
      IMPLICATIONS: Haptotherapy as a type of complementary medicine is a potentially
      valuable and effective intervention to raise the well-being of patients with
      cancer undergoing invasive treatments like chemotherapy.

PMID- 16426799
TI  - Between control and freedom in the care for persons with Prader-Willi syndrome:
      an analysis of preferred interventions by caregivers.
AB  - OBJECTIVE: The present study examined caregivers' preferences for intervention
      strategies in dealing with the dilemma of respecting autonomy of intellectually
      disabled persons versus providing high-quality care. METHODS: Twenty-four parents
      and 14 professional caregivers of persons with Prader-Willi syndrome were asked
      to rate four different kinds of intervention strategies according to their
      preferred way of dealing with 8 presented cases. RESULTS: In general, caregivers
      preferred to intervene more actively in eating problems compared to behavioural
      problems, more in acute than in chronic situations, and more in situations at
      home than in community-based settings. Significant differences were found between
      parents and professionals. CONCLUSION: Parents and professionals prefer
      intervening above laissez-faire. Parents prefer active intervention stronger than
      professionals. PRACTICE IMPLICATIONS: Awareness of various intervention
      strategies can help caregivers to develop a practice that does justice to the
      need for intervention on the one hand, and the possibility of using a variety of
      intervention strategies on the other hand. Communication about intervention
      strategies might foster understanding between professional caregivers and parents
      and improve mutual cooperation.

PMID- 16426800
TI  - Once a week not enough, twice a week not feasible? A randomised controlled
      exercise trial in long-term care facilities [ISRCTN87177281].
AB  - OBJECTIVE: To evaluate the effectiveness of three different training protocols on
      physical function of older adults living in long-term care facilities. Emphasis
      was placed on feasibility in real-life situations. METHODS: Subjects (N=224) were
      randomised to 6 months of twice weekly (1) resistance training; (2) all-round
      functional-skills training; (3) a combination of both; or (4) a control program.
      Fitness and performance measures and self-reported disability were measured at
      baseline and after 24 weeks intervention. RESULTS: Attendance to the strength
      training was 76%, to the functional-skills training 70% and to the combined
      training 73%. In those who attended at least 75% of all classes (n=97) the
      functional-skills and combined training program improved several fitness and
      performance measures compared to the control group. CONCLUSION: Twice weekly
      functional-skills training, or a combination of resistance and functional-skills
      training can improve several fitness and performance measures of
      institutionalised older people. PRACTICE IMPLICATIONS: An important finding from
      our study was that less than twice a week exercise training is not enough for
      functional improvement, while it proved difficult for the elderly subjects to
      exercise twice weekly. Education on the health benefits of regular exercise, and
      a larger availability of classes in long-term care facilities may improve
      attendance.

PMID- 16426801
TI  - The ostrich strategy towards affective issues in alexithymic patients with
      fibromyalgia.

PMID- 16426802
TI  - Liver resection for primary hepatic neuroendocrine tumours: report of three cases
      and review of the literature.
AB  - Primary neuroendocrine tumours are rare especially in the liver, which is more
      often site of metastatic tumours. We report three cases of primary hepatic
      neuroendocrine tumours, which underwent hepatic resection. Review of the
      diagnostic and therapeutic approaches to these tumours are discussed.

PMID- 16426803
TI  - [Acute cardiovascular complications of cocaine. About two case reports].
AB  - Concerning any socioprofessional category, some addictive drugs like cocaine are
      responsible for many complications. The authors relate two case reports of young
      patients who suffered from cardiovascular accidents due to this drug. The first
      one was diagnosed with an ischemic stroke caused by carotid artery dissection and
      a leg distal vascular obliteration, the second one with a myocardial infarction
      with transient left ventricular dysfunction. Through these two case reports, the
      authors take stock of the pathophysiological and therapeutic knowledge of
      cardiovascular accidents after cocaine intake.

PMID- 16426805
TI  - [Spontaneous intracerebral haemorrhage following evacuation of chronic subdural
      haematoma].

PMID- 16426804
TI  - [Postoperative pneumonia: nosocomial, predictable, iatrogenic, preventable or
      not?].
AB  - We report the case of a 52-year-old man, ASA 3-4, malnourished, heavy smoker and
      drinker at the stage of chronic obstructive pulmonary disease and cirrhosis. The
      postoperative course of a cervical cancer surgery was complicated by a pneumonia
      with fatal outcome in the intensive care unit. Taking into account the patient's
      history and surgical requirements, this nosocomial infection did not appear
      easily preventable. The multiple risk factors and the few preventive measures
      usable were analyzed. In this context, the media and legal trend to make the
      doctors responsible for the nosocomial infections should be revised.

PMID- 16426806
TI  - [Bilateral tension pneumothorax after retrieval of transtracheal jet ventilation
      catheter].
AB  - We report a bilateral tension pneumothorax which occurred in a 36-year-old man
      after high-frequency jet ventilation (HFJV) for panendoscopy. The patient had
      been treated with radiotherapy and chemotherapy two years ago for an
      oropharyngeal adenocarcinoma, and by surgery for a recurrence. The incident
      occurred after a cough episode triggered by the withdrawal of the Ravussin
      transtracheal catheter. We are discussing the risk factors and the mechanisms of
      pneumothorax during HFJV with special emphasis on trapping and lung fibrosis.

PMID- 16426807
TI  - [Knowledge of Moroccan anaesthesists in paediatric postoperative analgesia].

PMID- 16426808
TI  - [A case of delayed fat embolism after a vertebral osteosynthesis].
AB  - A 37-year-old woman presented an acute respiratory distress syndrome six days
      after a post-traumatic vertebral osteosynthesis. First, a pulmonary embolism was
      suspected, and a thrombolysis realised. This diagnosis was secondary excluded,
      and the diagnosis of probable fatty embolism was established by the
      bronchoalveolar lavage. So, this case shows a delayed presentation of fatty
      embolism and permits a discussion about clinical presentation, and diagnosis
      methods of such pathology.

PMID- 16426809
TI  - Expression of OmpP2A and OmpP2B is not required for pustule formation by
      Haemophilus ducreyi in human volunteers.
AB  - Haemophilus ducreyi express two porin proteins, termed OmpP2A and OmpP2B. To test
      whether expression of OmpP2A and OmpP2B was necessary for virulence in humans,
      eight volunteers were experimentally infected with the parent (35000HP) in one
      arm and a double OmpP2A OmpP2B mutant (35000HP::P2AB) in the other arm. The
      pustule formation rates were 58.3% (95% CI, 33.2-83.5%) for the parent and 41.7%
      (95% CI, 19.3-64.0%) for the mutant (P=0.25). Biopsy of 35000HP and 35000HP::P2AB
      infected sites yielded similar amounts of bacteria in quantitative culture. These
      results indicate that expression of OmpP2A and OmpP2B is not necessary to
      initiate disease or to progress to pustule formation in humans.

PMID- 16426810
TI  - Visualizing fungal infections in living mice using bioluminescent pathogenic
      Candida albicans strains transformed with the firefly luciferase gene.
AB  - Animal studies with Candida albicans have provided models for understanding
      fungal virulence and antifungal drug development. To non-invasively monitor long
      term Candida murine infections, clinical isolates were stably transformed with a
      codon-optimized luciferase gene to constitutively express luciferase. Chronic
      systemic infections were established in mice with engineered strains, and
      bioluminescent signals were apparent from kidneys by non-invasive imaging using
      charged-coupled device cameras. These infections were established in immune
      competent mice, and bioluminescence was detectable in animals that showed no
      physiological consequence of infection, as well as those visually succumbing to
      the disease. Similarly, bioluminescence was measured from the vaginal tissue of
      mice infected vaginally. Fungal loads determined by plating vaginal lavages
      showed a similar pattern to the bioluminescent signals measured, and fungal
      infection could be detected in animals for over 30 days post infection by both
      modalities. The effect of the antifungal drug miconazole was tested in this
      model, and clearance in animals was apparent by both direct imaging and fungal
      load determination. The use of bioluminescence to monitor these and other models
      of Candida infections will greatly speed up the analysis of drug development
      studies, both in ease of visualizing infections and decreasing numbers of animals
      required to run such studies.

PMID- 16426811
TI  - Potential involvement of galectin-3 and SNAP23 in Aeromonas hydrophila cytotoxic
      enterotoxin-induced host cell apoptosis.
AB  - We investigated the potential of the cytotoxic enterotoxin (Act) of Aeromonas
      hydrophila to bind to 1869 human and 4319 yeast proteins, using protein
      microarray technology. Act was capable of binding nine different human proteins,
      including the SNARE complex scaffolding protein synaptosomal-associated protein
      23 (SNAP23), galectin-3, and guanylate kinase 1 (GUK-1). Act was also able to
      bind to four of the yeast proteins examined, which included the vesicle tethering
      protein Vsp52. We verified interaction of Act with murine and human SNAP23,
      galectin-3, and GUK-1 by sandwich Western blot analysis. In order to determine
      the physiological relevance of Act binding to these three proteins, we performed
      small interfering RNA (siRNA) gene knockdown experiments in RAW 264.7 cells, a
      murine macrophage cell line in which Act-induced signaling and cell death is well
      characterized. Based on real-time reverse transcriptase-polymerase chain
      reaction, siRNA transfection of RAW 264.7 cells with specific oligonucleotides
      reduced the expression of genes encoding SNAP23, galectin-3, and GUK-1 by 62, 63,
      and 99%, respectively. Knockdown of galectin-3 and SNAP23, but not GUK-1,
      significantly reduced Act-induced apoptosis of host cells, as determined by TUNEL
      (TdT-mediated dUTP nick end labeling) assay, lactate dehydrogenase release,
      Giemsa staining, and reduction in activation of caspase 3, compared to toxin
      treated macrophages that were transfected with a random sequence control siRNA.
      We also performed these assays using a human intestinal epithelial cell line (HT
      29) and observed a similar trend of galectin-3 and SNAP23 association with Act
      induced apoptosis. This is the first report of putative protein binding partners
      for this toxin and potential mediators/regulators of Act-induced apoptosis.

PMID- 16426814
TI  - Effects of vocal training and phonatory task on voice onset time.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to examine the temporal
      acoustic differences between trained singers and nonsingers during speech and
      singing tasks. METHODS: Thirty male participants were separated into two groups
      of 15 according to level of vocal training (ie, trained or untrained). The
      participants spoke and sang carrier phrases containing English voiced and
      voiceless bilabial stops, and voice onset time (VOT) was measured for the stop
      consonant productions. RESULTS: Mixed analyses of variance revealed a significant
      main effect between speech and singing for /p/ and /b/, with VOT durations longer
      during speech than singing for /p/, and the opposite true for /b/. Furthermore, a
      significant phonatory task by vocal training interaction was observed for /p/
      productions. CONCLUSIONS: The results indicated that the type of phonatory task
      influences VOT and that these influences are most obvious in trained singers
      secondary to the articulatory and phonatory adjustments learned during vocal
      training.

PMID- 16426813
TI  - Clinical characteristics and voice analysis of patients with mutational
      dysphonia: clinical significance of diplophonia and closed quotients.
AB  - The aim of this study was to investigate the acoustic and electroglottographic
      characteristics of patients with mutational dysphonia before and after voice
      therapy. The clinical records of 15 patients with mutational dysphonia were
      reviewed, and their voice recordings were analyzed with the help of the Lx Speech
      Studio program (Laryngograph Ltd, London, UK). After voice therapy combined with
      the manual compression method, the subjects' voices lowered in pitch and improved
      in quality. In addition, we classified the mutational dysphonia into four
      categories according to the presence of diplophonia and closed quotients. The
      most common type among the categories was characterized by a bimodal distribution
      of fundamental frequency (diplophonia), accompanied by a low closed quotient
      (falsetto voice) at high frequencies. However, the results also showed that
      mutational dysphonia cannot be generalized as always having a falsetto voice, as
      shown in other types. The effect of therapy was different for each type, and
      those cases with both diplophonia and a non-trained falsetto voice could be
      treated more readily. Consequently, the diplophonia and closed quotient, which
      were easily analyzed using Lx Speech Studio program, are important factors in the
      classification of mutational dysphonia. Identification of these characteristics
      may affect treatment choices, facilitate monitoring of the efficacy of therapy,
      and aid in estimating prognosis.

PMID- 16426812
TI  - Signal transduction events involved in human epithelial cell invasion by
      Campylobacter jejuni 81-176.
AB  - Analyses of invasive enteric bacteria (e.g. Shigella, Salmonella, Listeria, and
      Campylobacter) have shown that these pathogens initiate orchestrated signal
      transduction cascades in host cells leading to host cytoskeletal rearrangements
      that result in bacterial uptake. This current study was specifically aimed at
      examining the involvement of host membrane caveolae and certain protein kinases
      in epithelial cell invasion by C. jejuni strain 81-176, for which we have
      previously characterized the kinetics of entry and a unique microtubule-dependent
      mechanism of internalization. Utilizing in vitro cultured cell invasion assays
      with a gentamicin-kill step, disruption of membrane caveolae by pretreatment of
      INT407 cell monolayers with filipin III reduced C. jejuni 81-176 entry by >95%.
      Strain 81-176 uptake into INT407 cells was markedly inhibited by monolayer
      pretreatment with the protein kinase inhibitors genistein and staurosporine, or
      specific inhibitors of PI 3-kinase, wortmannin and LY294002. Western blot
      analysis using monoclonal anti-protein tyrosine phosphorylation antibody revealed
      distinctive changes during invasion in phosphorylation of at least nine proteins.
      Further inhibitor studies indicated that heterotrimeric G proteins, plus ERK and
      p38 MAP kinase activation are also involved in C. jejuni 81-176 invasion. These
      results suggest that C. jejuni 81-176 interact at host cell surface membrane
      caveolae with G protein-coupled receptors, which presumably trigger G-proteins
      and kinases to activate host proteins including PI 3-kinase and MAP kinases, that
      appear to be intimately involved in the events controlling 81-176
      internalization.

PMID- 16426815
TI  - Anti-recoverin antibodies induce an increase in intracellular calcium, leading to
      apoptosis in retinal cells.
AB  - Autoantibodies against recoverin, a Ca2+-binding protein found in patients with
      cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce
      their apoptosis via a mitochondrial pathway. The goal of this study was to
      investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal
      cells causes a change in intracellular Ca2+. Intracellular Ca2+ was measured
      using the Ca2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal
      cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and
      control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to
      the CAR patients' autoantibodies in vitro caused a significant increase in
      intracellular Ca2+, while non-specific antibodies did not induce such an effect.
      Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L
      type Ca2+ channel blocker, significantly suppressed the increase of Ca2+.
      Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl
      xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells
      also showed a decrease in cytosolic cytochrome c release and a decrease in
      caspase 3 activation, compared to cells treated only with Rec-1 antibody. The
      increase in the antibody-induced Ca2+ is at least in part dependent on
      extracellular Ca2+. Nifedipine was found to inhibit the entry of Ca2+ into the
      cells and to protect them from Rec-1-induced apoptosis. Increased levels of
      intracellular Ca2+ may lead to retinal dysfunction and degeneration in the CAR
      syndrome. Our results provide a molecular basis for the use of Ca2+ blockers in
      the treatment of the CAR syndrome.

PMID- 16426816
TI  - The mechanism of nasal tolerance in lupus prone mice is T-cell anergy induced by
      immature B cells that lack B7 expression.
AB  - To determine if B cells of lupus prone NZB mice possess intrinsic defects that
      directly lead or contribute to T-cell hyper-responsiveness, we injected age-, sex
      and MHC II-matched NZB and Balb/c mice with histone peptide H471 representing a
      dominant Th cell epitope in histone H4 of the nucleosome. We found that B220+ B
      cells of NZB mice express high levels of surface CD86 following antigen priming.
      We cocultured CD4+ T and B220+ B cells of naive or peptide primed NZB and Balb/c
      mice in the presence of peptide. Antigen presentation by autoimmune B cells of
      NZB mice induced hyper-responsiveness from normal CD4+ T cells of Balb/c mice. T
      cell hyper-responsiveness is a result of CD86 costimulation by B cells of NZB
      mice. Induction of nasal tolerance to H471 in NZB mice suppressed CD86 surface
      expression and led to downregulation of T-cell proliferative response and
      cytokine production. More interestingly, B220+ B cells from nasally tolerized NZB
      mice induced T-cell anergy to anti-CD3 and anti-CD28 antibody stimulation in
      vitro. The anergic T cells do not possess suppressive function in coculture with
      naive responder T cells nor produce suppressive cytokines interleukin 10 and
      transforming growth factor-beta in vitro.

PMID- 16426817
TI  - Pronunciation of the z in schizophrenia.

PMID- 16426819
TI  - DNA sequence analysis of rdxA and frxA from paired metronidazole-sensitive and 
      resistant Helicobacter pylori isolates obtained from patients with
      heteroresistance.
AB  - Genomic variations of rdxA and frxA genes in eight pairs of metronidazole (MTZ)
      sensitive and -resistant isolates of Helicobacter pylori were investigated. The
      paired strains from each single biopsy had identical lspA-glmM restriction
      fragment length polymorphism profiles, and the differences in MTZ susceptibility
      were mostly accounted for by mutations in the rdxA gene. Truncation of RdxA is
      associated with a minimum inhibitory concentration of 64-128 mg/L. Early
      truncation of FrxA was observed both in susceptible and resistant isolates of
      seven paired strains. Inactivation of frxA might play a significant role only in
      one low-level MTZ-resistant isolate where a missense mutation was found in the
      rdxA gene.

PMID- 16426818
TI  - Purification and characterization of thermoalkalophilic xylanase isolated from
      the Enterobacter sp. MTCC 5112.
AB  - Thermoalkalophilic Enterobacter sp. MTCC 5112 was isolated from a sediment sample
      collected from the Mandovi estuary on the west coast of India. This culture
      produced extracellular xylanase. The xylanase enzyme was isolated by ammonium
      sulfate (80%) fractionation and purified to homogeneity using size exclusion and
      ion exchange chromatography. The molecular mass of the xylanase was approximately
      43 kDa. The optimal pH of the xylanase activity was 9, and at room temperature it
      showed 100% stability at pH 7, 8 and 9 for 3 h. The optimal temperature for the
      enzyme activity was 100 degrees C at pH 9.0. At 80 degrees C and pH 9, 90% of the
      enzyme activity was retained after 40 min. At 70 and 60 degrees C, the enzyme
      retained 64% and 85% of its activity after 18 h, respectively, while at 50
      degrees C and pH 9 the enzyme remained stable for days. For xylan, the enzyme
      gave a K(m) value of 3.3 mg ml(-1) and a V(max) value of 5,000 micromol min(-1)
      mg(-1) when the reaction was carried out at 100 degrees C and pH 9. In the
      presence of metal ions such as Co(2+), Zn(2+), Fe(2+), Cu(2+), Mg(2+) and Ca(2+)
      the activity of the enzyme increased, whereas strong inhibition of enzyme
      activity was observed in the presence of Hg(2+) and EDTA. To the best of our
      knowledge, this is the first report on the production of xylanase by this
      bacterium.

PMID- 16426820
TI  - Mutant prevention concentration for ciprofloxacin and levofloxacin with
      Pseudomonas aeruginosa.
AB  - The mutant prevention concentration (MPC) was determined by population analysis
      using six fluoroquinolone-susceptible isolates of Pseudomonas aeruginosa applied
      to fluoroquinolone-containing agar plates. The MPCs were 3 mg/L and 9.5 mg/L for
      ciprofloxacin and levofloxacin, respectively. At high concentrations of either
      compound, single-step gyrA resistance mutants were recovered. Using a modified
      method for estimating the MPC, 151 clinical isolates were surveyed. Modal MPCs
      were 2 mg/L and 8 mg/L, respectively, for ciprofloxacin and levofloxacin. Thus,
      ciprofloxacin is three to four times more active than levofloxacin against
      resistant mutant subpopulations. For individual isolates, the MPC correlated
      poorly with the minimum inhibitory concentration (r(2) = 0.41 and 0.39 for
      ciprofloxacin and levofloxacin, respectively).

PMID- 16426821
TI  - Protein adsorption and wetting of the protein adsorbed surfaces studied by a new
      type of laser reflectometer.
AB  - We have devised a new type of laser reflectometer that can measure adsorption
      behavior of (bio)-polymers, such as proteins, on the substrate surface and also
      the wetting for the surface of adsorbed layer of such (bio)-polymers. The
      adsorption and the wetting experiments can be conducted in a sequential manner
      using the same sample by this apparatus. So, the wetting of the surface of
      protein-adsorbed layer can be measured in virtually intact state. The
      reflectometry is based on the traditional optical polarimetry and the wetting
      measurement is due to the dropping time method (DTM) that has been reported
      before by the authors. The two methods are combined in an apparatus and hence we
      can correlate the wetting of protein layer adsorbed on the substrate surfaces
      with the amounts of protein molecules on the surface. As a model case we
      demonstrate the adsorption of several typical water soluble globular proteins on
      stainless steel surfaces. For this combination of the adsorbent with adsorbates,
      it is found that the water wetting of the protein adsorbed surface is closely
      related with the adsorbed amounts of proteins not depending on species.

PMID- 16426823
TI  - Elaboration of silica colloid/polymer hybrid support for oligonucleotide
      synthesis.
AB  - One way to increase the sensitivity of DNA diagnostic assays developed on
      microarrays is to improve the solid phase that allows the extraction of the
      target from a biological sample, before detection. Two parameters are influencing
      the performances of this capture step: (i) the specific surface area being
      offered for the capture and (ii) the number and the accessibility of
      oligonucleotide probes immobilized on the surface. In this context, we have
      developed an attractive approach which fulfills these two points. Our strategy
      was to elaborate a new material of high specific surface area, suitable to serve
      as support for both solid-phase oligonucleotide synthesis and in vitro diagnostic
      assay. This material has consisted of aggregates of colloidal amino-silica
      nanoparticles covalently linked by poly(ethylene oxide) (PEO) arms. The
      aggregation of amino-silica particles in the presence of reactive bis-isocyanate
      PEO was achieved in a controlled manner. The aggregate size and structure were
      examined by microscopy. The specific surface area of this material was measured
      by nitrogen adsorption technique. The composition of aggregate was studied by
      thermogravimetry and X-ray photoelectron spectroscopy. Then, this material has
      been successfully used as support for oligonucleotide synthesis of high yield and
      purity. The resulting system will be further evaluated in a diagnostic assay on a
      microarray.

PMID- 16426822
TI  - Langmuir monolayer properties of the fluorinated-hydrogenated hybrid amphiphiles
      with dipalmitoylphosphatidylcholine (DPPC).
AB  - Surface pressure-area (pi-A), surface potential-area (DeltaV-A), and dipole
      moment-area (mu( perpendicular)-A) isotherms were obtained for the Langmuir
      monolayer of two fluorinated-hydrogenated hybrid amphiphiles (sodium phenyl 1-[(4
      perfluorohexyl)-phenyl]-1-hexylphosphate (F6PH5PPhNa) and (sodium phenyl 1-[(4
      perfluorooctyl)-phenyl]-1-hexylphosphate (F8PH5PPhNa)), DPPC and their two
      component systems at the air/water interface. Monolayers spread on 0.02 M Tris
      buffer solution (pH 7.4) with 0.13M NaCl at 298.2K were investigated by the
      Wilhelmy method, ionizing electrode method and fluorescence microscopy. Moreover,
      the miscibility of two components was examined by plotting the variation of the
      molecular area and the surface potential as a function of the molar fraction for
      the fluorinated-hydrogenated hybrid amphiphiles on the basis of the additivity
      rule. The miscibility of the monolayers was also examined by construction of two
      dimensional phase diagrams. Furthermore, assuming the regular surface mixture,
      the Joos equation for analysis of the collapse pressure of two-component
      monolayers allowed calculation of the interaction parameter (xi) and the
      interaction energy (-Deltaepsilon) between the fluorinated-hydrogenated hybrid
      amphiphiles and DPPC. The observations by a fluorescence microscopy also
      supported our interpretation as for the miscibility in the monolayer state.
      Comparing the monolayer behavior between the two binary systems, no remarkable
      difference was found among various aspects. Among the two combinations, the mole
      fraction dependence in monolayer properties was commonly classified into two
      ranges: 0 <or= X <or= 0.3 and 0.3 < X <or = 1. Dependence of the chain length of
      fluorinated part was reflected for the molecular packing and surface potential.

PMID- 16426825
TI  - [Interventional digestive endoscopy in pediatrics].
AB  - Interventional endoscopy concerns the therapeutic acts carried out by endoscopic
      way at the level of the digestive tract. It is realized under general anaesthesia
      and it has profited from recent progress of the material (endoscopes and
      accessories). Some acts are realized in a current way in paediatrics: extraction
      of foreign body, dilation of oesophageal stenosis, gastrostomy. Other indications
      are rarer. In these cases, interventional endoscopy is usually done with the
      collaboration of the adult endoscopists, whose field of activity in
      interventional endoscopy is far much broader.

PMID- 16426824
TI  - Non-secretory exocytoses in the brain.
AB  - Regulated exocytosis, the process by which the membrane of specific cytoplasmic
      organelles fuse with the plasma membrane in response to adequate stimulation, is
      most often considered to serve only for the discharge of secretory products, in
      the brain especially neurotransmitters and peptides. Growing evidence
      demonstrates however that non-secretory exocytoses, aimed at the insertion at the
      cell surface of the organelle membrane, are of great physiological importance and
      may also have critical roles in specific diseases. Recently, two groups of non
      secretory exocytoses have been identified: those aimed at the transfer to the
      cell surface of specific proteins, that we have proposed to be called the protein
      exposing exocytoses; and those aimed at the enlargement of the surface itself,
      the expansive exocytoses. Here we present the existing knowledge about three
      types of non-secretory exocytoses that occur in the brain: the protein-exposing
      exocytoses that transfer ionic receptors to the postsynaptic membrane, the best
      known example being that of the glutamatergic AMPA receptor, a main actor of
      synaptic plasticity; the expansive exocytosis necessary for the growth of nerve
      fibres; and the rapid exocytosis of enlargeosomes, that can induce considerable
      expansion of the cell surface area in a variety of cells types, including the
      astrocytes.

PMID- 16426826
TI  - Studies on the stability of the chloramphenicol in the microemulsion free of
      alcohols.
AB  - Microemulsion composed of Span20 + Tween20 isopropyl myristate (IPM) + H2O were
      investigated as potential drug delivery systems for eye drops. The system is
      important in that all its components are food grade so that the microemulsion is
      almost free of toxicity and irritation. The phase transition was investigated
      using the electrical conductivity measurements. The chloramphenicol is used to
      treat the eye diseases such as trachoma and keratitis. However, this drug in the
      common eye drops hydrolyzes easily. The main product of the hydrolysis is glycol.
      Here, the chloramphenicol was trapped into the oil-in-water (o/w) microemulsions
      free of alcohols. Its stability was investigated by the high performance liquid
      chromatography (HPLC) assays in the accelerated experiments of 3 months. The
      location of the chloramphenicol molecules in the microemulsion formulations was
      determined by means of dynamic light scattering (DLS) and 1H NMR spectroscopy.
      The results of HPLC revealed that the content of the glycols in the microemulsion
      formulation was much lower than that in the commercial eye drops at the end of
      the accelerated experiments. It implied that the stability of the chloramphenicol
      in the microemulsion formulations was increased remarkably. The results of DLS
      and NMR confirmed that the chloramphenicol molecules should be trapped into the
      hydrophilic shells of the microemulsion drops, which were composed of many
      oxyethylene groups. The benzene rings of the chloramphenicol molecules were near
      the group of alpha2-CH2 and the oxyethylene groups of the surfactant molecules.
      It was this reason that enabled the chloramphenicol molecules in the
      microemulsions to be screened from the bulk water and its stability to be
      increased remarkably.

PMID- 16426827
TI  - Safety assessment of high fructose corn syrup (HFCS) as an ingredient added to
      cigarette tobacco.
AB  - A tiered testing strategy has been developed to evaluate the potential for new
      ingredients, tobacco processes, and technological developments to alter the
      biological activity that results from burning tobacco. A series of studies was
      initially conducted with cigarettes containing 3% high fructose corn syrup (HFCS)
      as an alternate tobacco casing material to corn syrup/invert sugar, including
      determination of selected mainstream cigarette smoke (MS) constituent yields,
      Ames assay, sister chromatid exchange (SCE) assay in Chinese hamster ovary (CHO)
      cells, a 30-week dermal tumor-promotion evaluation of cigarette smoke condensate
      (CSC) in SENCAR mice, and a 13-week subchronic inhalation study of MS in Sprague
      Dawley rats. A second series of studies was conducted with cigarettes containing
      3%, 4% and 5% HFCS including MS chemistry, Ames assay, SCE assay in CHO cells,
      and a neutral red cytotoxicity assays. Collectively, mainstream smoke chemistry,
      genotoxicity, dermal tumor-promotion, and inhalation toxicity studies
      demonstrated no differences between cigarettes with 3% HFCS and cigarettes with
      3% corn syrup/invert sugar. Also, mainstream smoke chemistry and genotoxicity of
      cigarettes with 4% and 5% HFCS were not different from cigarettes with 3% HFCS.
      In conclusion, the addition of up to 5% HFCS to cigarette does not alter the
      mainstream smoke chemistry or biological activity of mainstream smoke or
      mainstream smoke condensate as compared to cigarettes with 3% corn syrup/invert
      sugar with regard to the parameters investigated and presented.

PMID- 16426828
TI  - Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER
      stress-dependent Neuro2a cell death via protein kinase C pathway.
AB  - In many types of neurodegeneration, neuronal cell death is induced by endoplasmic
      reticulum (ER) stress. Hence, natural products able to reduce ER stress are
      candidates for use in the attenuation of neuronal cell death and, hence, in the
      reduction of the damage, which occurs in neurodegenerative disease. In this
      study, we investigated ER stress-reducing natural products from an edible
      mushroom, Hericium erinaceum. As a result of screening by cell viability assay on
      the protein glycosylation inhibitor tunicamycin-induced (i.e., ER stress
      dependent) cell death, we found that dilinoleoyl-phosphatidylethanolamine (DLPE)
      was one of the molecules effective at reducing ER stress-dependent cell death in
      the mouse neuroblastoma cell line Neuro2a cells. A purified DLPE, commercially
      available, also exhibited a reducing effect on this ER stress-dependent cell
      death. Therefore, we concluded that DLPE has potential as a protective molecule
      in ER stress-induced cell death. From the structure of DLPE, it was hypothesized
      that it might activate protein kinase C (PKC). The activity of PKC-epsilon, a
      novel-type PKC, was increased by adding DLPE, and PKC-gamma, a conventional-type
      PKC, was activated on the coaddition of diolein and DLPE, as shown by in vitro
      enzyme activity analysis. The protecting activity of DLPE was attenuated in the
      presence of a PKC inhibitor GF109203X but not completely diminished. Therefore,
      DLPE can protect neuronal cells from ER stress-induced cell death, at least in
      part by the PKC pathway.

PMID- 16426829
TI  - Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes.
AB  - There is increasing evidence that dysregulation of energy homeostasis is
      associated with colorectal carcinogenesis. Epidemiological data have consistently
      demonstrated a positive relation between increased body size and colorectal
      malignancy, whereas mechanistic studies have sought to uncover obesity-related
      carcinogenic pathways. The phenomenon of "insulin resistance" or the impaired
      ability to normalize plasma glucose levels has formed the core of these pathways,
      but other mechanisms have also been advanced. Obesity-induced insulin resistance
      leads to elevated levels of plasma insulin, glucose and fatty acids. Exposure of
      the colonocyte to heightened concentrations of insulin may induce a mitogenic
      effect within these cells, whereas exposure to glucose and fatty acids may induce
      metabolic perturbations, alterations in cell signaling pathways and oxidative
      stress. The importance of chronic inflammation in the pathogenesis of obesity has
      recently been highlighted and may represent an additional mechanism linking
      increased adiposity to colorectal carcinogenesis. This review provides an
      overview of the epidemiology of body size and colorectal neoplasia and outlines
      current knowledge of putative mechanisms advanced to explain this relation.
      Family based studies have shown that the propensity to become obese is heritable,
      but this is only manifest in conditions of excess energy intake over expenditure.
      Inheritance of a genetic profile that predisposes to increased body size may also
      be predictive of colorectal cancer. Genomewide scans, linkage studies and
      candidate gene investigations have highlighted more than 400 chromosomal regions
      that may harbor variants that predispose to increased body size. The genetics
      underlying the pathogenesis of obesity are likely to be complex, but variants in
      a range of different genes have already been associated with increased body size
      and insulin resistance. These include genes encoding elements of insulin
      signaling, adipocyte metabolism and differentiation, and regulation of energy
      expenditure. A number of investigators have begun to study genetic variants
      within these pathways in relation to colorectal neoplasia, but at present data
      remain limited to a handful of studies. These pathways will be discussed with
      particular reference to genetic polymorphisms that have been associated with
      obesity and insulin resistance.

PMID- 16426830
TI  - The dietary hydrolysable tannin punicalagin releases ellagic acid that induces
      apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial
      pathway.
AB  - Polyphenol-rich dietary foodstuffs have attracted attention due to their cancer
      chemopreventive and chemotherapeutic properties. Ellagitannins (ETs) belong to
      the so-called hydrolysable tannins found in strawberries, raspberries, walnuts,
      pomegranate, oak-aged red wine, etc. Both ETs and their hydrolysis product,
      ellagic acid (EA), have been reported to induce apoptosis in tumour cells.
      Ellagitannins are not absorbed in vivo but reach the colon and release EA that is
      metabolised by the human microflora. Our aim was to investigate the effect of a
      dietary ET [pomegranate punicalagin (PUNI)] and EA on human colon cancer Caco-2
      and colon normal CCD-112CoN cells. Both PUNI and EA provoked the same effects on
      Caco-2 cells: down-regulation of cyclins A and B1 and upregulation of cyclin E,
      cell-cycle arrest in S phase, induction of apoptosis via intrinsic pathway (FAS
      independent, caspase 8-independent) through bcl-XL down-regulation with
      mitochondrial release of cytochrome c into the cytosol, activation of initiator
      caspase 9 and effector caspase 3. Neither EA nor PUNI induced apoptosis in normal
      colon CCD-112CoN cells (no chromatin condensation and no activation of caspases 3
      and 9 were detected). In the case of Caco-2 cells, no specific effect can be
      attributed to PUNI since it was hydrolysed in the medium to yield EA, which
      entered into the cells and was metabolised to produce dimethyl-EA derivatives.
      Our study suggests that the anticarcinogenic effect of dietary ETs could be
      mainly due to their hydrolysis product, EA, which induced apoptosis via
      mitochondrial pathway in colon cancer Caco-2 cells but not in normal colon cells.

PMID- 16426831
TI  - Conjugated docosahexaenoic acid inhibits lipid accumulation in rats.
AB  - Conjugated linoleic acid (CLA), which contains a conjugated double-bond system,
      and n-3 highly unsaturated fatty acids such as docosahexaenoic acid (DHA) are
      widely known to improve lipid metabolism. To examine the possibility that a fatty
      acid with a combination of these structural features might have stronger
      physiological effects, we prepared conjugated DHA (CDHA) by alkaline
      isomerization of DHA and examined its effects on lipid and sugar metabolism in
      rats. Rats were force fed with 200 mg of test oils [linoleic acid (LA), DHA, CLA
      or CDHA] everyday for 4 weeks. Compared with the animals from the other groups,
      those in the CDHA group showed a significant weight loss in white adipose tissue
      (57% of adipose tissue weight in the LA group) and significant decreases in the
      levels of liver triacylglycerol (TG; 65% of TG level in the LA group) as well as
      total cholesterol (TC; 88% of TC level in the LA group), indicating suppression
      of lipid accumulation in the liver and adipose tissue. In addition, plasma TG and
      TC levels significantly decreased (69% of TG level and 82% of TC level in the LA
      group), indicating improved lipid metabolism. In the liver, the fatty acid
      synthesis system was inhibited and the fatty acid beta-oxidation system was
      activated, whereas the free fatty acid, glucose and tumor necrosis factor alpha
      levels in the plasma were lowered following CDHA administration. Hence, intake of
      CDHA appears to suppress the accumulation of fat in the liver and epididymal
      adipose tissue and improves lipid and sugar metabolism in rats.

PMID- 16426832
TI  - Reversal of chemical-induced liver fibrosis in Wistar rats by puerarin.
AB  - Puerarin is a major isoflavonoid compound isolated from Pueraria lobata, an
      edible vine used widely for various medicinal purposes. It has been used for
      centuries in China to counteract alcohol intoxication. However, the effects of
      puerarin on chemical-induced liver fibrosis have not been reported. In the
      present study, we investigated the effects of puerarin on liver fibrosis in
      Wistar rats induced by alcohol plus carbon tetrachloride administration. Liver
      fibrosis was produced in rats by treatment with a mixture (50% alcohol, 8 g/kg
      per day; corn oil, 2 g/kg per day; pyrazole, 24 mg/kg per day; ig) once a day and
      by intraperitoneal injection of 0.25 ml/kg of a 25% solution of carbon
      tetrachloride in olive oil twice a week for 8 weeks. After 8 weeks, treatment
      with puerarin (0.4 and 0.8 g/kg ig, daily for 4 weeks) was conducted to examine
      its therapeutic effects. At the same time, the model group and treatment group
      continued to receive the chemical mixture, while the control group received
      saline instead of the chemical mixture. Upon pathological examination, the
      puerarin-treated rats significantly reversed the symptoms of liver fibrosis and
      other hepatic lesions. Serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST), as indexes of hepatic cell disruption, were reduced with
      puerarin treatment, whereas no significant effect was discovered in the levels of
      alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities. A
      significant increase in apoptosis of activated hepatic stellate cell (HSC) was
      found by flow cytometric analysis of the hepatic tissues. And the expression of
      bcl-2 mRNA was down-regulated after puerarin administration. Consequently, all
      these results showed that puerarin could effectively reverse chemical-induced
      liver fibrosis in experimental rats, via the recovery of hepatic injury as well
      as the induction of apoptosis in activated HSC.

PMID- 16426833
TI  - Methane flux and oxidation at two types of intermediate landfill covers.
AB  - Methane emissions were measured on two areas at a Florida (USA) landfill using
      the static chamber technique. Because existing literature contains few
      measurements of methane emissions and oxidation in intermediate cover areas, this
      study focused on field measurement of emissions at 15-cm-thick non-vegetated
      intermediate cover overlying 1-year-old waste and a 45-cm-thick vegetated
      intermediate cover overlying 7-year-old waste. The 45 cm thick cover can also
      simulate non-engineered covers associated with older closed landfills. Oxidation
      of the emitted methane was evaluated using stable isotope techniques. The
      arithmetic means of the measured fluxes were 54 and 22 g CH(4) m(-2)d(-1) from
      the thin cover and the thick cover, respectively. The peak flux was 596 g m(-2)d(
      1) for the thin cover and 330 g m(-2)d(-1) for the thick cover. The mean percent
      oxidation was significantly greater (25%) at the thick cover relative to the thin
      cover (14%). This difference only partly accounted for the difference in
      emissions from the two sites. Inverse distance weighing was used to describe the
      spatial variation of flux emissions from each cover type. The geospatial mean
      flux was 21.6 g m(-2)d(-1) for the thick intermediate cover and 50.0 g m(-2)d(-1)
      for the thin intermediate cover. High emission zones in the thick cover were
      fewer and more isolated, while high emission zones in the thin cover were
      continuous and covered a larger area. These differences in the emission patterns
      suggest that different CH(4) mitigation techniques should be applied to the two
      areas. For the thick intermediate cover, we suggest that effective mitigation of
      methane emissions could be achieved by placement of individualized compost cells
      over high emission zones. Emissions from the thin intermediate cover, on the
      other hand, can be mitigated by placing a compost layer over the entire area.

PMID- 16426834
TI  - Effects of the forced ventilation on composting of a solid olive-mill by-product
      ("alperujo") managed by mechanical turning.
AB  - The evaluation of the most suitable aeration technology for olive-mill by-product
      "alperujo" (AL) composting was carried out by using two identical piles prepared
      by mixing AL with a bulking agent (fresh cow bedding) and a mature compost (as
      inoculant). Forced ventilation was employed in conjunction with mechanical
      turning in one of the piles, whereas only mechanical turning was used in the
      other pile. These two treatment methods were evaluated by assessing process
      efficiency and end-product quality. The results show that the composting process
      was completed in less time when forced ventilation was coupled with mechanical
      turning. A slight delay in the evolution of pH, C/N ratio, and biodegradation of
      fats and organic matter was observed when only turning was employed. However, the
      recommended method for composting AL was mechanical turning without forced
      ventilation since the composition of the end-product in this case was comparable
      to the composted AL using forced ventilation coupled with mechanical turning.
      Furthermore, there were substantial economic savings by selecting mechanical
      turning alone, which included capital costs for equipment.

PMID- 16426835
TI  - Sensitive determination of ciprofloxacin and norfloxacin in biological fluids
      using an enzymatic rotating biosensor.
AB  - The high sensitivity that can be attained using an enzymatic system and mediated
      by catechol has been verified by on-line interfacing of a rotating biosensor and
      continuous-flow/stopped-flow/continuous-flow processing. Horseradish peroxidase,
      HRP, [EC 1.11.1.7], immobilized on a rotating disk, in the presence of hydrogen
      peroxide catalyzed the oxidation of catechol, whose back electrochemical
      reduction was detected on glassy carbon electrode surface at -200mV. Thus, when
      ciprofloxacin (CF) or norfloxacin (NF) was added to the solution, these
      piperazine-containing compounds participate in Michael addition reactions with
      catechol to form the corresponding aminoquinone derivative, decreasing the peak
      current obtained in proportion with the increase of its concentration. CF was
      used as the model piperazine-containing compound for the study. The influence of
      indicator composition on the nature of the analytical response has been assessed
      through examining the electrochemical properties of three derivatives.
      Interference by electroactive species (ascorbate, urate, and tyrosine) and other
      physiological constituents (cysteine, glutathione) has also been assessed.

PMID- 16426836
TI  - An automated cell analysis sensing system based on a microfabricated rheoscope
      for the study of red blood cells physiology.
AB  - An automated rheoscope has been developed, utilizing a microfabricated glass flow
      cell, high speed camera and advanced image-processing software. RBCs suspended in
      a high viscosity medium were filmed flowing through a microchannel. Under these
      conditions, RBCs exhibit different orientations and deformations according to
      their location in the velocity profile. The rheoscope system produces valuable
      data such as velocity profile of RBCs, spatial distribution within a microchannel
      and deformation index (DI) curves. The variation of DI across the channel height,
      due to change in shear stress, was measured carrying implications for
      diffractometry methods. These curves of DI were taken at a constant flow rate and
      cover most of the relevant shear stress spectrum. This is an improvement of the
      existing techniques for deformability measurements and may serve as a diagnostic
      tool for certain blood disorders. The DI curves were compared to measurements of
      the flowing RBCs velocity profile. In addition, we found that RBCs flowing in a
      microchannel are mostly gathered in the center of the flow and maintain a
      characteristic spatial distribution. The spatial distribution in this region
      changes slightly with increasing flow rate. Hence, the system described, provides
      means for examining the behavior of individual RBCs, and may serve as a
      microfabricated diagnostic device for deformability measurement.

PMID- 16426837
TI  - Area and layer patterning in the developing cerebral cortex.
AB  - Two anatomical patterns characterize the neocortex, and both are essential for
      normal cortical function. First, neocortex is divided into anatomically distinct
      and functionally specialized areas that form a species-specific map. Second,
      neocortex is composed of layers that organize cortical connectivity. Recent
      studies of layer and area development have used time-lapse microscopy to follow
      cortical cell division and migration, gene arrays to find layer- or area-
      specific regulatory genes, time- and region- specific manipulations of candidate
      genes, and optical imaging to compare area maps in wild type with genetically
      altered mice. New observations clarify the molecular and cellular mechanisms that
      generate each pattern, and stress the links between layer and area formation.

PMID- 16426838
TI  - Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with
      advanced solid tumours: Is rash associated with treatment outcome?
AB  - In this analysis of the safety and efficacy of BAY 43-9006 (sorafenib) -- a
      novel, oral multi-kinase inhibitor with effects on tumour and its vasculature --
      pooled data were obtained from four phase I dose-escalation trials. Time to
      progression (TTP) was compared in patients with/without grade 2 skin
      toxicity/diarrhoea. Grade 3 hand-foot skin reactions (HFS; 8%) and diarrhoea (6%)
      were common. At the recommended 400mg bid dose for phase II/III trials (RDP), 15%
      of patients experienced grade 2/3 HFS, and 24% experienced grade 2/3 diarrhoea.
      Sorafenib induced stable disease for 6 months in 12% of patients (6% stabilized
      for 1 year). Patients receiving sorafenib doses at or close to the RDP, who
      experienced skin toxicity/diarrhoea, had a significantly increased TTP compared
      with patients without such toxicity (P < 0.05). Sorafenib was well tolerated at
      the RDP, and induced sustained disease stabilization, particularly in patients
      with skin toxicity/diarrhoea.

PMID- 16426839
TI  - Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal
      adenocarcinoma.
AB  - The tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/Apo2L)
      is a member of the TNF superfamily that preferentially induces apoptosis in
      cancer cells, while sparing normal cells. TRAIL induces apoptosis by interacting
      with its receptors TRAIL-R1 and TRAIL-R2. Recently, new humanized agonistic anti
      TRAIL-R1 and anti-TRAIL-R2 antibodies have been developed, and are undergoing
      phase I/II clinical trails. Esophageal adenocarcinoma (EA) is associated with
      significantly poor outcome and is rapidly increasing in incidence in the United
      States and Western Europe, with virtually no effective non-surgical treatment.
      The aim of this study was to determine whether human EA tissue express TRAIL-R1
      and/or TRAIL-R2, and whether EA cell lines Bic-1 and Seg-1 expresses functional
      TRAIL-R1 and/or TRAIL-R2. The expression of TRAIL-R1 and TRAIL-R2 was determined
      in sections from 18 human EA by immunohistochemistry (IHC). Sixteen (89%) of the
      EA expressed TRAIL-R1 and 17 (94%) expressed TRAIL-R2. Both cell lines were found
      to express TRAIL-R1 and TRAIL-R2 by western blot analysis, IHC, and flow
      cytometry. The fully human agonistic TRAIL-R1 (HGS-ETR1) and TRAIL-R2 (HGS-ETR2)
      antibodies induced apoptosis in Bic-1 and Seg-1 cells in a time and dose
      dependent manner. Our results show that the vast majority of primary human EA
      express TRAIL-R1 and TRAIL-R2 and that EA cells lines express functional TRAIL-R1
      and TRAIL-R2. Targeting of these receptors by agonist monoclonal antibodies may
      be of therapeutic value in patients with EA.

PMID- 16426840
TI  - Stem cell transplantation: risk factors for psychiatric morbidity.
AB  - The aim of this study was to determine the risk factors for psychiatric disorder
      in haematological cancer patients during hospitalization for stem cell
      transplantation. In this 3-year prospective study, 220 patients received stem
      cell transplantation at a single institution. Structured psychiatric interviews
      applying standardized diagnostic criteria were performed at hospital admission
      and weekly during hospitalization until discharge or death, yielding a total of
      1,062 interviews. Psychiatric disorder (any depressive, anxiety, or adjustment
      disorder) prevalence at the time of hospital admission was 21% and psychiatric
      disorder incidence during post-admission follow-up was 22%. After adjusting for
      multiple confounders in multivariate logistic regression analyses, we found that
      younger age, women, a past psychiatric history, lower functional status, pain,
      smoking cessation, and higher regimen-related toxicity were significantly
      associated with psychiatric disorder risk. Our study findings may help to improve
      identification of the patients most at risk for psychiatric disturbances during
      hospitalization for stem cell transplantation.

PMID- 16426841
TI  - Clinico-histologic parameters of osteosarcoma patients with late relapse.
AB  - Primary high-grade intramedullary osteosarcoma of the extremities is a clinically
      aggressive bone tumour. There is an ongoing effort to further improve efficacy of
      neo-adjuvant chemotherapy and reduce chemotoxicity by trying to identify
      osteosarcoma patients who are at risk of treatment failure as well as to identify
      those who can do with less chemotherapy. In only 5% of patients, first distant
      metastasis or local relapse occurs 5 years or more after initial treatment for
      osteosarcoma. Patients and physicians can therefore easily erroneously consider a
      patient with osteosarcoma cured if he or she is disease-free for more than 5
      years following diagnosis and treatment. To investigate if these rare late
      relapsing patients are characterised by specific clinico-pathological features,
      we examined clinical and histological variables of late relapse (first local
      recurrence or metastasis 5 years or more after initial diagnosis) out of a total
      of 2,243 patients, with a special interest in the histological osteosarcoma
      subtype. In total, 33 patients had a documented relapse 5 years or more after
      diagnosis. Half of the patients had good response (>or=90% necrosis) to pre
      operative chemotherapy and the other half a poor response (<90% necrosis) and
      late relapses seemed to be more frequently proportionately in those who had a
      good initial response to chemotherapy. The occurrence of late relapse did not
      appear to be associated with age or gender. Although not statistically
      significant, there was a trend for patients with a chondroblastic subtype of
      osteosarcoma, or a location in the tibia or fibula, to have a higher risk for
      late relapse.

PMID- 16426842
TI  - RARRES1 expression is significantly related to tumour differentiation and staging
      in colorectal adenocarcinoma.
AB  - Retinoic acid receptor responder 1 (RARRES1) is a retinoid regulated gene. Its
      expression is frequently down-regulated through DNA hypermethylation in several
      types of malignant tissues. This study investigated the clinical significance of
      RARRES1 protein and its association with RARRES3 protein expression in 161 (26
      adenoma, 13 distal normal mucosa and 122 primary colorectal adenocarcinoma)
      paraffin-embedded colorectal tissues by immunohistochemistry. RARRES1 protein was
      detected at the highest levels in terminally differentiated cells of normal
      mucosal tissues and all 26 adenoma tissues. Among 122 colorectal adenocarcinomas,
      the poorly differentiated adenocarcinomas and Dukes' stage D tumours showed a
      significant decrease in RARRES1 expression (P < 0.001 and P < 0.01,
      respectively). RARRES1 expression was significantly (P < 0.001) correlated with
      RARRES3 expression, which was positively associated with tumour differentiation
      (P < 0.001). Difference in expression of RARRES1 among 119 patients had no
      apparent effect on patient survival. Our results suggest the role of RARRES1 in
      colorectal epithelial differentiation, and the down-regulation of RARRES1 is
      related to stage D progression.

PMID- 16426844
TI  - The 'Lost Tribe' and the need for a promised land: the challenge of cancer in
      teenagers and young adults.

PMID- 16426845
TI  - Enhancing performance in anaerobic high-solids stratified bed digesters by straw
      bed implementation.
AB  - Anaerobic high-solids single-stage stratified bed digesters have been found to be
      simple and flexible design candidates for small-scale reactors located in medium-
      to low-technology environments. In the present study, wheat straw was used as the
      starter material for the stratified bed. Upon green mass feeding, the
      anaerobically stabilised straw bed functioned both as a biofilm support and as a
      particulate filter. It enabled a direct onset of 7 kg VSm(-3) batch loads, added
      twice a week, and permitted a low but consistent bed permeability during feeding
      at an average superficial flow velocity of 1 m d(-1) to be achieved. Fed-batch
      tests with sugar beet tops in pilot- and laboratory-scale setups at an average
      loading rate of 2 kg VSm(-3) d(-1) resulted in average biogas production rates of
      1.2-1.4 m3 m(-3) d(-1) and methane yields of 0.31-0.36 m3 kg(-1) VS(added). At
      the end of the laboratory-scale feeding trial, the 200 day old straw bed had
      compacted to 50% of its initial volume, without any negative effects on
      performance being detectable.

PMID- 16426843
TI  - Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin
      B1 expression in a p53-independent manner.
AB  - A unique in vitro system has been developed in our lab that consists of normal
      enterocytes derived from the rat ileum (IEC-18 cells) and their transformed
      derivatives with c-K-ras (R1 cells), anti-sense bak (B3 cells) and cyclin D1 (D1
      cells). R1 and B3 cells express high level of COX-2 protein and PGE2. IEC 18 and
      D1 cells express negligible amount of COX-2, and produce very low level of PGE2.
      A relatively low dose of celecoxib (5-10 microM) induced G2/M arrest, followed by
      induction of apoptosis in the transformed but not in the normal cells. Down
      regulation of cyclin B1 and up-regulation of p21 expressions independent of p53
      might have cause this cell cycle block. Growth inhibition was related to COX-2
      function with 90-95% reduction in PGE2 production. These findings may be of
      clinical importance, since low concentration of celecoxib can be achieved in
      human serum following standard anti-inflammatory (100-200 mg bid) regime.

PMID- 16426847
TI  - Fast pyrolysis of rice husk: Product yields and compositions.
AB  - A series of pyrolysis oils and chars were prepared from agricultural by-product
      rice husk by the lab-scale fast pyrolysis system using induction heating. The
      effect of process parameters such as pyrolysis temperature, heating rate, holding
      time, nitrogen gas flow rate, condensation temperature and particle size on the
      pyrolysis product yields and their chemical compositions was examined. The
      maximum oil yield of over 40% was obtained at the proper pyrolysis conditions.
      The chemical characterization by elemental, calorific, spectroscopic and
      chromatographic studies showed that the pyrolysis oils derived from the fast
      pyrolysis of rice husk contained considerable amounts of carbonyl groups and/or
      oxygen content, resulting in low pH and low heating values.

PMID- 16426846
TI  - Cadmium accumulation and its effects on metal uptake in maize (Zea mays L.).
AB  - The effects of different concentrations of Cd on growth of maize (Zea mays L.)
      and metal uptake were investigated. Cd accumulations in roots and shoots and the
      interactions among other metals (Mn, Fe, Cu and Zn) were analyzed using
      inductively coupled plasma atomic emission spectrometry (ICP-AES). The
      concentrations of cadmium chloride (CdCl(2).2.5H2O) used ranged from 10(-4) M to
      10(-6) M. Cd had stimulatory effects during the first 5 days on root length of
      Nongda No. 108 at 10(-6) M and 10(-5) M Cd concentrations. Seedlings exposed to
      10(-4) M Cd solution exhibited substantial growth reduction, and root growth even
      stopped. Root growth of Liyu No. 6 was stimulated at concentrations of 10(-5) M
      and 10(-6) M Cd during the entire experiment (15 days). Cadmium inhibited root
      growth of Liyu No. 6 at 10(-4) M Cd after 10 days of treatment. The Cd
      accumulation in roots and shoots of the two cultivars increased significantly (P
      < 0.05) with increasing Cd concentration and duration of treatment. Cadmium
      concentrated mainly in the roots, and small amounts were transferred to shoots.
      The proportion of Cd in the roots of Nongda No. 108 decreased with increases in
      Cd concentrations and duration of treatment, except for the group exposed to 10(
      4) M Cd. In Liyu No. 6, the proportion of Cd in the root decreased progressively
      with an increase in Cd concentrations. Liyu No. 6 has a greater ability to remove
      Cd from solution and accumulate it when compared with Nongda No. 108. Liyu No. 6
      can be considered a Cd-hyperaccumulator, according to the current accepted shoot
      concentration that defines hyperaccumulation as 0.01% (w/w) for cadmium. This
      cultivar, producing many roots and a high biomass and with great ability to
      accumulate Cd can play an important role in the treatment of soils stressed by
      Cd.

PMID- 16426849
TI  - Mild and efficient oxidation of Hantzsch 1,4-dihydropyridines with sodium
      periodate catalyzed by a new polystyrene-bound Mn(TPP)Cl.
AB  - Mild and efficient oxidation of Hantzsch 1,4-dihydropyridines with sodium
      periodate catalyzed by Mn(TTP)Cl supported on polystyrene-bound imidazole is
      reported. This heterogeneous catalyst is of great stability and reusability in
      the oxidation of 1,4-dihydropyridines with sodium periodate without significant
      loss of its catalytic activity.

PMID- 16426848
TI  - Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.
AB  - A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing
      propargylic ether P1' groups, was explored. In particular, compound 5h has
      excellent in vitro potency against isolated TACE enzyme and in cells, oral
      activity in a model of TNF-alpha production and a collagen-induced arthritis
      model, was selected as a clinical candidate for the treatment of RA.

PMID- 16426850
TI  - Prediction of hERG potassium channel affinity by the CODESSA approach.
AB  - The problem of predicting torsadogenic cardiotoxicity of drugs is afforded in
      this work. QSAR studies on a series of molecules, acting as hERG K+ channel
      blockers, were carried out for this purpose by using the CODESSA program.
      Molecules belonging to the analyzed dataset are characterized by different
      therapeutic targets and by high molecular diversity. The predictive power of the
      obtained models was estimated by means of rigorous validation criteria implying
      the use of highly diagnostic statistical parameters on the test set, other than
      the training set. Validation results obtained for a blind set, disjoined from the
      whole dataset initially considered, confirmed the predictive potency of the
      models proposed here, so suggesting that they are worth to be considered as a
      valuable tool for practical applications in predicting the blockade of hERG K+
      channels.

PMID- 16426851
TI  - Antimalarial activity: a QSAR modeling using CODESSA PRO software.
AB  - A quantitative structure-activity relationship (QSAR) modeling of the
      antimalarial activity of two diverse sets of compounds for each of two strains D6
      and NF54 of Plasmodium falciparum is presented. The molecular structural features
      of compounds are presented by molecular descriptors (geometrical, topological,
      quantum mechanical, and electronic) calculated using the CODESSA PRO software.
      Satisfactory multilinear regression models were obtained for data sets of the D6
      and NF54 strains, with R2 = 0.84 and 0.89, respectively. The models were also
      satisfactorily validated internally. The descriptors involved in these equations
      were related to the mechanism of antimalarial protection.

PMID- 16426852
TI  - Synthesis and TNF-alpha inducing activities of mycoloyl-arabinan motif of
      mycobacterial cell wall components.
AB  - The extract of the cell wall skeleton of Bacillus Calmette-Guerin (BCG-CWS) from
      Mycobacterium bovis is known to be an activator of innate immunity. Synthesis of
      pentaarabinofuranoside as part of the arabinan moiety of BCG-CWS was achieved by
      double alpha-arabinofuranosylation followed by double beta-arabinofuranosylation
      with orthogonally protected donors. Mycolic esters of the arabinan in the
      terminal lipo-arabinan motif of BCG-CWS were synthesized through alkylation of
      unprotected mycolic acid with bis- and tetra-tosylates of pentaarabinofuranoside.
      A series of compounds were subjected to a tumor necrosis factor alpha (TNF-alpha)
      secretion-inducing assay, disclosing aspects of the structure-activity
      relationship which should be useful in finding the site of the activity.

PMID- 16426853
TI  - Preparation and tumor affinity testing of the radioiodinated
      tetrahydroisoquinoline derivative [123I]TIC(OH) for targeting prostate cancer.
AB  - This work describes the synthesis and tumor affinity testing of 8-[123I]iodo-l
      1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid [ITIC(OH)], a cyclic
      non-naturally occurring amino acid as an imaging probe for prostate cancer.
      Parameters for labelling were optimized with regard to the amount of precursor,
      the temperature and time. Thereafter, ITIC(OH) was evaluated in terms of its
      uptake in primary human PC-3 and DU-145 prostate cancer cells, followed by
      analysis of the underlying mechanisms of the radioactivity accumulation in tumor
      cells. No-carrier-added ITIC(OH) was obtained in 80+/-15% radiochemical yield and
      >98% radiochemical purity by a one-step radioiodination, using IODO-GEN as
      oxidant. The total synthesis time was less than 30 min, and compatible with a
      clinical routine production. ITIC(OH) accumulated intensively in primary human
      prostate cancer cells. The radioactivity incorporation in tumor following a 10
      min incubation at 37 degrees C/pH 7.4 varied from 35% to 58% of the total loaded
      activity per 10(6) tumor cells (355-540 cpm/1000 cells). Inhibition experiments
      revealed that ITIC(OH) was taken up into tumor by an active transport different
      from the common amino acid carrier systems, including the sodium-dependent system
      A and B+,0, and the sodium-independent L- and ASC-type transporter. In contrast,
      the cellular incorporation was dependent on the membrane potential and correlated
      with the activity of the mitochondria. In conclusion, the specific and high-level
      accumulation of ITIC(OH) in human prostate carcinoma cells, indicates that the
      new radiopharmaceutical is a good candidate for further in vivo investigations to
      ascertain its potential as an imaging probe for prostate cancer by SPET.

PMID- 16426855
TI  - Metastatic and fatal mitral valve obstruction during pneumonectomy for large
      pulmonary hemangiopericytoma.

PMID- 16426854
TI  - Effect of trypsin inhibitor from Crotalaria pallida seeds on Callosobruchus
      maculatus (cowpea weevil) and Ceratitis capitata (fruit fly).
AB  - A proteinaceous trypsin inhibitor was purified from Crotalaria pallida seeds by
      ammonium sulfate precipitation, affinity chromatography on immobilized trypsin
      Sepharose and TCA precipitation. The trypsin inhibitor, named CpaTI, had M(r) of
      32.5 kDa as determined by SDS-PAGE and was composed of two subunits with 27.7 and
      5.6 kDa linked by disulfide bridges. CpaTI was stable at 50 degrees C and lost
      40% of activity at 100 degrees C. CpaTI was also stable from pH 2 to 12 at 37
      degrees C. CpaTI weakly inhibited chymotrypsin and elastase and its inhibition of
      papain, a cysteine proteinase, were indicative of its bi-functionality. CpaTI
      inhibited, in different degrees, digestive enzymes from Spodoptera frugiperda,
      Alabama argillacea, Plodiainterpunctella, Anthonomus grandis and Zabrotes
      subfasciatus guts. In vitro and in vivo susceptibility of Callosobruchus
      maculatus and Ceratitis capitata to CpaTI was evaluated. C. maculatus and C.
      capitata enzymes were strongly susceptible, 74.4+/-15.8% and 100.0+/-7.3%,
      respectively, to CpaTI. When CpaTI was added to artificial diets and offered to
      both insect larvae, the results showed that C. maculatus was more susceptible to
      CpaTI with an LD(50) of 3.0 and ED(50) of 2.17%. C. capitata larvae were more
      resistant to CpaTI, in disagreement with the in vitro effects. The larvae were
      more affected at lower concentrations, causing 27% mortality and 44.4% mass
      decrease. The action was constant at 2-4% (w/w) with 15% mortality and 38% mass
      decrease.

PMID- 16426856
TI  - Direct access valve replacement (DAVR) - are we entering a new era in cardiac
      surgery?
AB  - OBJECTIVE: This study validates the off-pump antegrade trans-ventricular route
      for ultrasound-guided direct access aortic valve replacement. Direct access
      aortic valve replacement using a transthoracic and valved stent-based approach
      offers numerous advantages over the remote access percutaneous approach and may
      one day provide an alternative treatment modality for aortic valve disease.
      METHODS: Valved stents were implanted off-pump in 17 pigs (72.10+/-8.4 kg) via
      the direct access transapical approach using a left-sided mini-thoracotomy and
      continuous ultrasonic and fluoroscopic guidance. Acute valved stent function was
      studied with intravascular and two-dimensional intracardiac ultrasound. The
      invasive valve gradient was assessed with pull-back pressure catheter. All valved
      stents were tested in vitro before insertion. Macroscopic analysis was performed
      at necropsy. RESULTS: In 11 of the 17 pigs, valved stents were delivered to the
      target site over the native aortic valve leaflets without interference of
      coronary blood flow and with good acute valve function. Three valved stents were
      deployed supra-annularly, two of those occluded the right coronary orifice and
      one the left coronary orifice, leading to fatal outcomes. Three valved stents
      dislodged into the left ventricle, one because of size-mismatch and two because
      of failure to unfold correctly. In 11 properly sized and deployed valved stents,
      two showed a moderate and one a severe paravalvular leak. CONCLUSIONS: Seventeen
      pigs underwent direct access valve replacement of the aortic valve with
      deployment of a valved stent into the native aorta. Eleven valves observed for an
      average 5-h period showed satisfactory, postimplantation valve function.

PMID- 16426858
TI  - Antigen-specific T cell responses: determination of their frequencies, homing
      properties, and effector functions in human whole blood.
AB  - Several prevalent and life-threatening agents enter the organism via the mucosa.
      In this case, a mucosal cellular immune response is essential for protection and
      is therefore considered the main objective of vaccination. The frequency of
      antigen-specific CD4+ and CD8+ T cells can be determined directly in human whole
      blood by a combination of surface marker and intracellular cytokine staining.
      Immune cells primed in the mucosal compartment also migrate through the blood and
      can be identified by expression of the gut-specific homing receptor alpha4beta7.
      Simultaneously, these lymphocytes can be functionally characterized regarding
      their differentiation status by analysis of CD45RO and CD27 expression and
      effector functions by measuring intracellular perforin or granzyme B content.
      Thus, the technique described in the paper is a powerful tool for clinical
      monitoring of the total cellular immune response to complex antigens during
      infection or vaccination.

PMID- 16426857
TI  - Differential properties of adult rat and mouse brain-derived neural
      stem/progenitor cells.
AB  - Adult neurogenesis from neural stem/progenitor cells occurs in discrete regions
      of the central nervous system of all mammals, but the mechanisms regulating
      endogenous neurogenesis are poorly understood. Advances in understanding the
      neurogenesis depend on knowing their intrinsic properties and responses to
      environmental signals that control their behavior. Before these issues can be
      addressed, it is necessary to know whether there are significant species-specific
      differences in the properties of the stem/progenitor cells derived from CNS of
      two commonly studied model systems, mouse and rat. We found major differences
      between rat and mouse stem/progenitor cell proliferation in response to various
      substrates, mitogenic growth factors and heparin and to the influence of
      differentiation factors on generation of neurons and glia. Thus, extrapolation of
      cell properties from one species to another based on studies of these cells
      should be made with caution.

PMID- 16426859
TI  - Expression and purification of the intact cytoplasmic domain of the human ephrin
      receptor A2 tyrosine kinase in Escherichia coli.
AB  - The ephrin receptor A2 (EphA2) is an integral membrane protein tyrosine kinase
      and a member of the Eph family, the largest known family of receptor tyrosine
      kinases. EphA2 overexpression is sufficient to transform normal epithelial cells
      into an aggressive, metastatic phenotype. In normal cells, EphA2 negatively
      regulates cell growth and invasiveness. Here we report expression of the intact
      cytoplasmic domain (juxtamembrane linker, tyrosine kinase, and sterile alpha
      motif domains) of the human EphA2 receptor in an Escherichia coli system. The
      expressed protein was purified to near homogeneity by use of metal chelation
      chromatography combined with removal of vector-encoded tags by specific
      proteolysis. The cytoplasmic domains of EphA2 are expressed as an active kinase,
      with the expressed protein found to contain phosphorylated tyrosine residues. In
      addition, protein tyrosine phosphorylation appears only after EphA2 expression is
      induced and is removable with alkaline phosphatase treatment. The enzyme was
      purified 5-fold in yields that average 10-30 mg/L of active EphA2 cytoplasmic
      domains, which will now be used for further biophysical and structural
      characterization.

PMID- 16426860
TI  - Morphological and structural aspects of the giant starch granules from Phajus
      grandifolius.
AB  - The morphology and structure of giant starch granules from the pseudo-bulbs of
      Phajus grandifolius were investigated, using a number of microscopy techniques
      together with synchrotron radiation microdiffration analysis. Most of the
      granules, which had sizes between 100 and 200 microm, occurred as ogival
      particles with the hilum or proximal end located at the apex of the granules. A
      small percentage of granules held a protuberance extending orthogonally to the
      underlying parent granule. Growth rings were observed in all granules: strongly
      curved close to the hilum, but planar toward the distal end of the granules or in
      the protuberances. Specific mechanical disruption followed by enzymatic digestion
      revealed the susceptibility of the disorganized parts of the growth rings, which
      were preferentially carved away during the digestion, leaving behind the better
      organized domains. Microdiffraction analysis achieved with synchrotron radiation
      revealed the crystalline features of the granules and provided orientation maps
      of the amylopectin molecules in the various parts of the granules. In simple
      ogival granules the amylopectin molecules were uniformly oriented with their axes
      running from the hilum toward the distal end of the granule. In granules with a
      protuberance, the axes of the amylopectin molecules kept their direction in the
      parent granule, but took an orthogonal direction in the protuberance. The
      occurrence of these morphological and structural features is tentatively
      correlated with the mode of growth of these granules.

PMID- 16426861
TI  - The anisotropic material constitutive models for the human cornea.
AB  - This paper presents an anisotropic analysis model for the human cornea. The model
      is based on the assumption that the fibrils in the cornea are organised into
      lamellae, which may have preferential orientation along the superior-inferior and
      nasal-temporal directions, while the alignment of lamellae with different
      orientations is assumed to be random. Hence, the cornea can be regarded as a
      laminated composite shell. The constitutive equation describing the relationships
      between membrane forces, bending moments, and membrane strains, bending
      curvatures are derived. The influences of lamella orientations and the random
      alignment of lamellae on the stiffness coefficients of the constitutive equation
      are discussed.

PMID- 16426862
TI  - Identification and expression analysis of cDNAs encoding channel catfish type I
      interferons.
AB  - Previously a cDNA encoding a putative interferon gene, designated CF IFN-1, was
      identified from a catfish EST library. However, its constitutive expression,
      absence of a signal peptide, and apparently low level of biological activity
      suggested that this cDNA likely encoded an expressed pseudogene. Since Southern
      blot analysis suggested the presence of two to three IFN genes, additional cDNAs
      were generated from catfish fibroblast and lymphoid cell lines using primers
      designed to conserved regions of zebrafish and catfish interferon. Using this
      approach, three novel CF IFN genes, two of which likely encode functional
      interferon molecules, were identified. At the amino acid level, similarity among
      CF IFNs ranged from 71% to 82%, whereas similarity to other fish IFNs ranged from
      15% to 35%. Although CF IFN-3, like CF IFN-1, lacks a signal peptide, CF IFN-2
      and -4 appear to encode full-length, signal sequence-bearing genes. Consistent
      with their putative identification as functional genes, CF IFN-2 and -4 were not
      expressed in unstimulated cell lines, and CF IFN-2 was rapidly upregulated in CCO
      cells in response to virus infection or treatment with dsRNA. Moreover, as with
      salmon, fugu, and zebrafish interferon genes, CF IFN-1 contained four introns
      whose locations were conserved not only with respect to other fish IFNs, but also
      with respect to mammalian IFN-lambda. While it is likely that CF IFNs represent
      Type I IFNs, several characteristics preclude assigning these cytokines to any
      particular subfamily.

PMID- 16426863
TI  - Unique multimeric immunoglobulin crosslinking in four species from the family
      Gadidiae.

PMID- 16426864
TI  - Fate of intraperitoneally injected fluorescent microspheres in developing
      Ictalurus punctatus.
AB  - Fluorescent microspheres (FMS) were injected intraperitoneally into channel
      catfish fry at 2 days post hatch (dph), 1, 2, 3, 4 and 8 weeks post hatch (wph).
      The FMS were observed in the vasculature almost immediately after injection in
      all age groups except 2 dph. Fluorescent microspheres were observed within
      mononuclear phagocytes in the vasculature after 0.16 dph in all age groups.
      Fluorescent microspheres were first phagocytized in the coelomic cavity
      immediately after injection, while the majority of coelomic FMS were phagocytized
      between 0.16 and 1 dph for all ages. Enzyme cytochemical staining indicated that
      both polymorphonuclear (neutrophilic granulocytes) and mononuclear phagocytes had
      phagocytized FMS in the coelomic cavity and organs, with a predominance of FMS
      found in mononuclear phagocytic cells in all age groups across all sample
      periods. The predominant organs associated with the observed cellular responses
      were the posterior kidney, spleen, and anterior kidney. Splenic organization and
      melanomacrophage development and activity were more pronounced as the fish aged
      from 2 wph on. Particulate clearance rates were faster in the 2 dph and 1 wph
      fish than the older ages of fish. These results suggest that to facilitate
      particulate retention, channel catfish should be vaccinated at 4 wph or older.

PMID- 16426865
TI  - Gender difference analysis of cortical thickness in healthy young adults with
      surface-based methods.
AB  - We have examined gender differences of cortical thickness using a 3-D surface
      based method that enables more accurate measurement in deep sulci and localized
      regional mapping compared to volumetric analyses. Cortical thickness was measured
      using a direct method for calculating the distance between corresponding vertices
      from inner and outer cortical surfaces. We normalized cortical surfaces using 2-D
      surface registration and performed diffusion smoothing to reduce the variability
      of folding patterns and to increase the power of the statistical analysis. In
      stereotaxic space, significant localized cortical thickening in women was found
      extensively in frontal, parietal and occipital lobes, including the superior
      frontal gyrus (SFG), superior parietal gyrus (SPG), inferior frontal gyrus (IFG)
      and postcentral gyrus (PoCG) in the left hemisphere and mostly in the parietal
      lobe, including the SPG in the right hemisphere. In the temporal lobe, small
      regions of the left and right caudal superior temporal gyrus (STG) and the left
      temporal pole showed significantly greater cortical thickness in women. The
      temporal lobe shows relatively less significant thickening than other lobes in
      both hemispheres. In native space, significantly greater cortical thickness in
      women was detected in left parietal region, including SPG and PoCG. No
      significant local increases of cortical thickness were observed in men in both
      spaces. These findings suggest statistically significant cortical thickening in
      women in localized anatomical regions, which is consistent with several previous
      studies and may support a hypothesis of sexual dimorphism.

PMID- 16426866
TI  - Postmortem high-resolution 3-dimensional imaging of the primate brain: blockface
      imaging of perfusion stained tissue.
AB  - Modern anatomy of the brain is primarily concerned with visualizing contrast
      between tissue elements and with 3-dimensional (3-D) reconstruction. The first
      objective relies on specific neuroanatomical and imaging protocols, the latter on
      proper alignment of serial cross-sectional anatomy. We present a method that
      meets these goals at a resolution that allows for the structural delineation in
      the primate central nervous system. Methylene blue was administered by perfusion
      to the intact brain of three rhesus macaques thereby staining the neuropil in the
      cortex and gray nuclei of the brain in situ. Subsequent dissection and serial
      sectioning revealed excellent contrast in the tissue and showed clear boundaries
      between anatomical structures. We captured sequential images of the block surface
      of the brain before each serial section was cut from the specimen by means of a
      digital camera mounted directly over the microtome stage and the brain. We
      developed a suite of algorithms to automate the alignment, segmentation,
      normalization, and intensity correction for the series of blockface images. These
      digital images were the basis for 3-D reconstruction of the brains.

PMID- 16426867
TI  - Data-driven parceling and entropic inference in MEG.
AB  - In Amblard et al. [Amblard, C., Lapalme, E., Lina, J.M. 2004. Biomagnetic source
      detection by maximum entropy and graphical models. IEEE Trans. Biomed. Eng. 55
      (3) 427--442], the authors introduced the maximum entropy on the mean (MEM) as a
      methodological framework for solving the magnetoencephalography (MEG) inverse
      problem. The main component of the MEM is a reference probability density that
      enables one to include all kind of prior information on the source intensity
      distribution to be estimated. This reference law also encompasses the definition
      of a model. We consider a distributed source model together with a clustering
      hypothesis that assumes functionally coherent dipoles. The reference probability
      distribution is defined as a prior parceling of the cortical surface. In this
      paper, we present a data-driven approach for parceling out the cortex into
      regions that are functionally coherent. Based on the recently developed
      multivariate source pre-localization (MSP) principle [Mattout, J., Pelegrini
      Issac, M., Garnero, L., Benali, H. 2005. Multivariate source pre-localization
      (MSP): Use of functionally informed basis functions for better conditioning the
      MEG inverse problem. NeuroImage 26 (2) 356--373], the data-driven clustering
      (DDC) of the dipoles provides an efficient parceling of the sources as well as an
      estimate of parameters of the initial reference probability distribution. On MEG
      simulated data, the DDC is shown to further improve the MEM inverse approach, as
      evaluated considering two different iterative algorithms and using classical
      error metrics as well as ROC (receiver operating characteristic) curve analysis.
      The MEM solution is also compared to a LORETA-like inverse approach. The data
      driven clustering allows to take most advantage of the MEM formalism. Its main
      trumps lie in the flexible probabilistic way of introducing priors and in the
      notion of spatial coherent regions of activation. The latter reduces the
      dimensionality of the problem. In so doing, it narrows down the gap between the
      two types of inverse methods, the popular dipolar approaches and the distributed
      ones.

PMID- 16426868
TI  - Pliocene and Pleistocene diversification and multiple refugia in a Eurasian shrew
      (Crocidura suaveolens group).
AB  - We sequenced 998 base pairs (bp) of mitochondrial DNA cytochrome b and 799 bp of
      nuclear gene BRCA1 in the Lesser white-toothed shrew (Crocidura suaveolens group)
      over its geographic range from Portugal to Japan. The aims of the study were to
      identify the main clades within the group and respective refugia resulting from
      Pleistocene glaciations. Analyses revealed the Asian lesser white-toothed shrew
      (C. shantungensis) as the basal clade, followed by a major branch of C.
      suaveolens, subdivided sensu stricto into six clades, which split-up in the Upper
      Pliocene and Lower Pleistocene (1.9-0.9 Myr). The largest clade, occurring over a
      huge range from east Europe to Mongolia, shows evidence of population expansion
      after a bottleneck. West European clades originated from Iberian and Italo
      Balkanic refugia. In the Near East, three clades evolved in an apparent hotspot
      of refugia (west Turkey, south-west and south-east of the Caucasus). Most clades
      include specimens of different morphotypes and the validity of many taxa in the
      C. suaveolens group has to be re-evaluated.

PMID- 16426870
TI  - Phosphorylation state of CREB in the rat hippocampus: a molecular switch between
      spatial novelty and spatial familiarity?
AB  - The activation of cAMP response element-binding protein (CREB) after a learning
      experience is a common feature in the formation of several associative memories.
      We recently demonstrated that the increase in the hippocampal phosphorylated CREB
      (pCREB) levels 1 h after a short exploration of an open field (OF) was associated
      to detection of spatial novelty and was not related to the memory formation of
      habituation in this non-associative learning paradigm. Moreover, after a long
      training of three OF sessions, hippocampal pCREB levels were below to that
      observed in control rats. The present results show that such decrease does not
      correlate with memory retrieval or improvement in long-term memory of
      habituation. Instead, it is associated with the familiarity to the arena. Our
      experiments revealed that the relevant variable to induce CREB deactivation was
      the prolonged exploration of the arena (30 min). A 15 min OF exploration was
      ineffective. Furthermore, the last 5 min period of a prolonged exploration was
      crucial to change CREB phosphorylation state: when exploration took place in a
      novel arena the level of pCREB increased; in contrast, when it was performed in
      the familiar OF, pCREB levels decreased. Taken as a whole, our results suggest
      that CREB phosphorylation state in the hippocampus switches in response to
      exposure to a novel or to a familiar spatial environment.

PMID- 16426869
TI  - The use of levetiracetam in refractory status epilepticus.
AB  - Six patients with status epilepticus (SE) of various etiologies refractory to at
      least two antiepileptic drugs (AEDs) had complete cessation of their seizures
      following administration of oral levetiracetam (LEV). Seizure types included
      convulsive, focal, and nonconvulsive status epilepticus. Effective doses of
      levetiracetam ranged from 500 to 3000 mg/day, achieving seizure control within 12
      96 h. No significant adverse events were noted. Adjunctive levetiracetam should
      be considered for patients with status epilepticus unresponsive to initial
      therapy.

PMID- 16426871
TI  - Pre-arteriotomy guidewire access (PAGA): a crucial maneuver for securing inflow
      and/or outflow in patients with bulky iliofemoral occlusive disease undergoing
      combined (open/endovascular) procedures.
AB  - PURPOSE: To present our technique of pre-arteriotomy guidewire access (PAGA).
      SUMMARY: Placement of a guidewire across inflow lesions before performing the
      arteriotomy during combined endovascular/open procedures while treating patients
      with complex iliofemoral occlusive disease is a crucial maneouvre. We routinely
      utilize this approach in patients in whom endarterectomy and/or patch angioplasty
      is planned as the central part of the revascularization procedure, or when we
      find an unsuspected severely diseased EIA in a patient undergoing leg
      revascularization.

PMID- 16426872
TI  - Should pre-operative troponin be a standard requirement in patients undergoing
      major lower extremity amputation?
AB  - OBJECTIVES: The objective of this study was to ascertain the benefit of routine
      pre-operative cardiac troponin I (cTnI) measurement in patients undergoing major
      lower extremity amputation for critical limb ischaemia. DESIGN: This was a
      prospective, blinded observational study. METHODS: All patients scheduled for
      lower extremity amputation, without evidence of unstable coronary artery disease
      were recruited prospectively over a period of 1 year. In addition to routine pre
      operative evaluation, a blood sample was taken for measurement of serum cTnI.
      Post-operative screening was conducted for cardiac events with patients followed
      up to 6 weeks. RESULTS: Ten of the 44 patients included suffered a non-fatal
      myocardial infarction or died from a cardiac cause post-operatively. A rise in
      pre-operative cTnI was associated with a very poor outcome (two cardiac deaths
      and one post-operative myocardial infarction) and was the only significant
      predictor of post-operative cardiac events. CONCLUSION: Routine pre-operative
      cTnI measurement may be of use to identify patients at high risk of cardiac
      complication who would benefit from optimization of cardiac status or in whom
      surgery could be deferred.

PMID- 16426873
TI  - Re: The influence of subintimal angioplasty on level of amputation and limb
      salvage rates in lower limb critical ischaemia: a 15-year experience.

PMID- 16426875
TI  - Clinical observations on the use of the muscle relaxant rocuronium bromide in the
      dog.
AB  - This study was designed to evaluate the effectiveness of neuromuscular blockade
      with rocuronium bromide (rocuronium) in eighty dogs anaesthetised for a variety
      of surgical procedures. Rocuronium 0.3 or 0.6 mg/kg (G03 and G06) was
      administered intravenously (IV) and neuromuscular function was monitored with an
      acceleromyograph. Lag time (LT) was >1 min in both groups. Onset time (OT) was
      2+/-0.9 and 1.1+/-0.6 min in the groups given 0.3 and 0.6 mg/kg, respectively.
      There was a significantly longer time of action with 0.6 mg/kg in contrast to 0.3
      mg/kg rocuronium. Time of no response (TonR) was 9.1+/-4.9-16.9+/-6.1 min in the
      groups given 0.3 and 0.6 mg/kg, respectively. The time from the end of injection
      until 25% recovery of the first twitch from the baseline value (T1(25)) was
      13.8+/-5.5 and 22.3+/-6.7 min in the groups given 0.3 and 0.6 mg/kg,
      respectively. T1(25-75) was similar in both groups. Total recovery to baseline
      values was achieved in 23.8+/-6.6 and 31.9+/-6.5 min in the groups given 0.3 and
      0.6 mg/kg, respectively (P<0.05). Premedication, maintenance agent, body position
      and stimulation site had no significant influence on the pharmacodynamic
      parameters in both groups. It was concluded that rocuronium is an effective non
      depolarising muscle relaxant in the dog under clinical conditions.

PMID- 16426874
TI  - Maternal determinants of embryonic cell fate.
AB  - How important is the contribution of mRNAs and proteins stored in the oocyte for
      determining the body plan of the Xenopus embryo? Here we review the current
      understanding of the roles of maternally supplied transcription factors,
      signaling molecules, and signaling regulators in establishing the ectoderm,
      mesoderm, and endoderm germ layers and the embryonic axes. Key essential
      asymmetries of VegT, Wnt11, and Ectodermin are described, as well as the
      complexity of maternal transcription factors that are involved in the initial
      expression of early zygotic genes.

PMID- 16426876
TI  - Genetic approaches to the improvement of fertility traits in the pig.
AB  - One of the major determinants for litter size in pigs is prenatal mortality. It
      occurs most frequently during the first few weeks of gestation and can be
      attributed to abnormalities in developmental processes during embryogenesis
      including trophoblastic elongation and blastocyst implantation. Improvement of
      litter size has been attempted by means of phenotypic selection. However, another
      promising approach in pursuit of this aim has been the use of genotypic
      information. Reproductive traits in general are well-suited for application of
      marker-assisted selection (MAS). The possibility of exerting selection criteria
      at the molecular level shortens the generation interval as the selection decision
      can take place early in the life of an animal. Moreover, in consideration of the
      sex-limited nature of reproductive traits, genotypic information allows for
      selection in the gender in which the trait cannot be directly observed.
      Accordingly, there has been considerable interest in mapping and identifying
      genes involved in the regulation of reproductive traits and in elucidating their
      expression patterns. This review offers a comprehensive, if not exhaustive,
      account of the efforts being made and the approaches currently used in this
      field. One approach has been to choose candidate genes a priori because of the
      physiological importance of the proteins they encode and their role in the
      reproduction of other mammals. The usefulness of candidate genes is then examined
      by association studies between genetic polymorphisms identified in the respective
      candidate genes and the phenotypic reproductive traits. The other approach
      discussed uses pre-existing or designed families for linkage analyses in order to
      map the location of quantitative trait loci (QTL) for the reproductive trait of
      interest. The results reported were not consistent among different studies but
      the QTL regions detected may be useful for identification of positional candidate
      genes in further molecular genetic studies. However, a better understanding of
      porcine reproduction requires that these functional genomic approaches are merged
      and integrated with detailed analyses of the proteome to establish linkages
      between predisposition and physiology.

PMID- 16426877
TI  - Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma
      concentrations in chronic pain patients treated with transdermal buprenorphine.
AB  - The present study was designed to study the impact of intermittent hemodialysis
      on the disposition of the partial agonist buprenorphine and its metabolite
      norbuprenorphine during therapy with transdermal buprenorphine in chronic pain
      patients with end-stage kidney disease. Ten patients (mean age 63 years) who had
      received transdermal buprenorphine for at least 1 week, were asked to provide
      blood samples immediately before and after hemodialysis. Blood samples were
      analysed for buprenorphine and its metabolite norbuprenorphine. The median
      buprenorphine plasma concentrations were found to be 0.16 ng/ml before and 0.23
      ng/ml after hemodialysis. A significant correlation between plasma levels and
      administered doses was observed (Spearman R=0.74; P<0.05). In three patients
      norbuprenorphine plasma levels were detected. No differences in pain relief
      before and after hemodialysis were observed. This investigation shows no elevated
      buprenorphine and norbuprenorphine plasma levels in patients with renal
      insufficiency receiving transdermal buprenorphine up to 70 microg/h. Furthermore,
      hemodialysis did not affect buprenorphine plasma levels, leading to stable
      analgesic effects during the therapy.

PMID- 16426878
TI  - The relationship between activity and pain in patients 6 months after lumbar disc
      surgery: do pain-related coping modes act as moderator variables?
AB  - BACKGROUND: In LBP patients, the relationship between pain and physical activity
      remains unclear. Whereas a negative relationship between pain and self-reported
      physical activity was found, this relation disappeared in the case of overt
      behavioral data (e.g., accelerometer). Cognitive-behavioral models of the
      development of chronic pain suggest subgroups with signs of physical underuse and
      overuse. AIMS: To examine if patients with pain-related adaptive, endurance and
      fear-avoidance coping differ in pain, self-reported physical function and overt
      physical activity 6 months after disc surgery. METHODS: 24 patients completed
      questionnaires (Von Korff chronic pain grade (CPG), Kiel pain inventory (KPI),
      Funktionsfragebogen Hannover-Rucken FFbH-R) and underwent an 8-h accelerometer
      assessment in their daily life (physical activity level (PAL), number of constant
      postures (CP)). The KPI differed between adaptive coping (AC) (N=9), fear
      avoidance coping (FAC) (N=1) and endurance coping (EC) (N=14). RESULTS: In the
      whole group, pain intensity was negative related to self-reported physical
      activity whereas PAL and CP displayed no correlation with pain. EC patients
      showed significantly higher pain scores and lower self-reported physical
      functioning compared to AC but the same level of PAL and furthermore, a
      significantly higher number of CPs in daily life. The visual inspection of the
      FAC patient revealed also high pain, low physical functioning and low overt
      physical activity. CONCLUSIONS: The assessment of pain-related coping modes
      yielded an important differentiation between subgroups of LBP patients 6 months
      after surgery. Endurance copers displayed signs of overuse in their daily
      behavior in spite of pain than adaptive copers. The one fear avoidance coper
      tends to do less physical activity in the sense of underuse.

PMID- 16426879
TI  - Growth, oxygen consumption, and protein and RNA synthesis rates in the yolk sac
      larvae of the African catfish (Clarias gariepinus).
AB  - Rapidly growing African catfish yolk sac larvae were investigated during the
      first 22 h after hatching. Body compartment protein concentration increased
      fourfold yet oxygen consumption remained constant (mean=21.3 +/- 3.2 nmol O2 mg(
      1) protein h(-1)), suggesting fast growth results mainly from yolk sac protein
      absorption. The protein synthesis rates at 1-2 and 5-6 h also equaled the highest
      conceivable rates of muscle protein synthesis; 11.6-11.9% and 7.4-7.9% day(-1),
      respectively. Therefore the corresponding energetic costs of protein synthesis
      were almost the theoretical minimum; 13.0 +/- 1.7-16.3 +/- 2.8 micromol O2 mg(-1)
      protein synthesised. Total protein synthesis expenditure (74.5-77.7 micromol O2
      g(-1) protein h(-1)) was also less than other yolk sac larvae. These protein
      synthesis rates resulted from high RNA concentrations (113.2 +/- 3.4 microg RNA
      mg(-1) protein) and were also correlated with RNA translational efficiency. High
      translational efficiency (1 h; 1.2+/-0.1 mg protein synthesised microg(-1) RNA
      day(-1)) equaled high synthesis rate (36.8 +/- 5.4 microg RNA microg(-1) DNA day(
      1)) and both declined over 22 h. This investigation suggests rapid growth
      combines growth efficiency and compensatory energy partitioning. This
      accommodates the ontogenetic and phylogenetic standpoints imposed by energy
      budget limitations.

PMID- 16426880
TI  - Effects of endurance training and acute exhaustive exercise on antioxidant
      defense mechanisms in rat heart.
AB  - We investigated whether 8-week treadmill training strengthens antioxidant enzymes
      and decreases lipid peroxidation in rat heart. The effects of acute exhaustive
      exercise were also investigated. Male rats (Rattus norvegicus, Sprague-Dawley
      strain) were divided into trained and untrained groups. Both groups were further
      divided equally into two groups where the rats were studied at rest and
      immediately after exhaustive exercise. Endurance training consisted of treadmill
      running 1.5 h day(-1), 5 days week(-1) for 8 weeks. For acute exhaustive
      exercise, graded treadmill running was conducted. Malondialdehyde level in heart
      tissue was not affected by acute exhaustive exercise in untrained and trained
      rats. The activities of glutathione peroxidase and glutathione reductase enzymes
      decreased by both acute exercise and training. Glutathione S-transferase and
      catalase activities were not affected. Total and non-enzymatic superoxide
      scavenger activities were not affected either. Superoxide dismutase activity
      decreased by acute exercise in untrained rats; however, this decrease was not
      observed in trained rats. Our results suggested that rat heart has sufficient
      antioxidant enzyme capacity to cope with exercise-induced oxidative stress, and
      adaptive changes in antioxidant enzymes due to endurance training are limited.

PMID- 16426881
TI  - Wound healing after excision of mantle tissue from the Akoya pearl oyster,
      Pinctada fucata.
AB  - Pearl oysters are usually sacrificed to donate mantle tissue for pearl
      production. However, if oysters are anaesthetized, they are able to survive
      mantle excision and regenerate this tissue. Mantle excision causes a large wound
      and severs the pallial artery that necessitates rapid wound repair to avoid death
      by bleeding. This study was undertaken to assess the wound healing process in the
      mantle of the Akoya pearl oyster, Pinctada fucata, following mantle excision.
      Forty-seven P. fucata were relaxed with 2.5 mL L(-1) propylene phenoxetol before
      mantle tissue was excised. Oysters were relaxed and sacrificed 1, 3, 6, 12, 25,
      36, 48, 66, 80 and 105 h after excision to assess mantle healing using
      histological techniques. Muscular contraction that effectively reduced the size
      of the wound was observed within 1 h after mantle excision. Accumulation of
      haemocytes and connective tissue occurred 3-6 h after excision and wound plugging
      was achieved within 6 h of excision. Proliferation of epithelial cells to cover
      the wound site was observed within the first 25 h after mantle excision and
      growth of connective tissue and formation of the pallial artery were observed
      within 105 h after mantle excision.

PMID- 16426882
TI  - Isolation of an eclosion hormone gene from the cotton bollworm, Helicoverpa
      armigera: temporal and spatial distribution of transcripts.
AB  - The cDNA encoding eclosion hormone (EH), which plays an integral role in
      triggering ecdysis behavior at the end of each molt, was cloned from the cotton
      bollworm, Helicoverpa armigera (Har) (Lepidoptera: Noctuidae). The EH polyprotein
      precursor contains a 26-amino acid signal peptide and a single 62-amino acid
      mature EH. Compared the mature Har-EH with other known EHs, it shows 94%, 84%,
      and 59% identities to Manduca sexta, Bombyx mori, and Drosophila melanogaster,
      respectively. Har-EH mRNA is expressed only in the brain by Northern blot and RT
      PCR, but not in other tissues. By in situ hybridization and immunocytochemistry,
      both Har-EH mRNA and protein are localized in two pairs of neurosecretory cells
      of the brain. Prior to a molt, expression level of Har-EH gene reaches the
      highest point, and then drops after molt. EH release is detected both centrally,
      within the ganglia, and peripherally, into the hemolymph. A peak of the EH titer
      in hemolymph measured by ELISA presents at ecdysis. These results are consistent
      with the biological function of Har-EH associated with ecdysis. Furthermore, Har
      EH gene is expressed throughout all of the developmental stages examined,
      implicating that the EH gene may possess other biological functions in post
      embryonic development other than triggering ecdysis behavior.

PMID- 16426883
TI  - Molecular cloning and gene expression of Spo11 during spermatogenesis in the
      Japanese eel, Anguilla japonica.
AB  - Spo11 is a protein involved specifically in the meiotic recombination in several
      species, however, it is little characterized in lower vertebrates. We identified
      a cDNA encoding Spo11 from the testis of Japanese eel, Anguilla japonica. The
      deduced amino acid sequence of eel Spo11 was more than 60% identical with human
      and mouse Spo11s. In order to examine changes in the expression and localization
      of Spo11 during spermatogenesis induced by the injection of human chorionic
      gonadotropin (hCG) and to compare with those of Dmc1, we generated specific
      antibodies against the eel Spo11 and Dmc1. In general, it is believed that Dmc1
      is a meiosis-specific protein, and the localization of Dmc1 in spermatocytes was
      confirmed also in Japanese eel. Spo11 transcripts were slightly detected in the
      testis after 1 day post-hCG injection by Northern blot analysis. Western blot
      analysis also indicated that Spo11 production began at day 1 after hCG injection.
      However, immunohistochemical observations showed that Spo11 was localized only in
      spermatocytes. In contrast, Dmc1 transcripts and the protein production were
      first detected at day 6 after hCG injection and increased along with the
      increment of spermatocytes. These results suggested that Spo11 was expressed in
      spermatogonia proliferated toward meiosis at quite low level that could not
      induce meiotic recombination, thereafter Spo11 expression increased and Dmc1
      expression was initiated in early meiotic prophase. Hence, the antibodies against
      eel Spo11 and Dmc1 generated in the present study can be use to detect germ cells
      in early meiotic prophase immunohistochemically. Importantly, it is suggested
      that germ cells, which are in quite earlier stage during meiotic prophase, can be
      detected by Spo11.

PMID- 16426884
TI  - Deoxyribonuclease II from the Icelandic scallop (Chlamys islandica): isolation
      and partial characterization.
AB  - A deoxyribonuclease (DNase) was isolated from viscera of the cold-adapted marine
      bivalve Icelandic scallop. The 42 kDa DNase was shown to be a single polypeptide
      which catalyses DNA hydrolysis in the absence of divalent cations. The isolated
      enzyme showed maximal activity at pH 6 and no activity above pH 7.2 against
      native DNA. The scallop DNase was slightly more susceptible to heat denaturation
      than porcine DNase II and makes double-strand breaks in circular DNA substrate as
      the porcine enzyme. The N-terminal sequence of the scallop DNase was shown to be
      closely similar to DNase II (EC 3.1.22.1) proteins from other organisms. The
      scallop DNase is in addition to plancitoxin I from A. planci, the only DNase II
      enzyme isolated from marine invertebrates.

PMID- 16426886
TI  - Analysis of the point mechanical impedance of fingerpad in vibration.
AB  - Biodynamic responses of the finger-hand-arm system, such as apparent mass and
      mechanical impedance, characterize the relationship between the motion of the
      finger-hand-arm system and the dynamic force acting on the driving point, and
      they are useful for vibration exposure assessment. In the present study, a two
      dimensional finite element (FE) model has been proposed to simulate the
      biodynamic responses of the fingerpad in vibration tests. The fingernail was
      supported by the rigid ground while the fingerpad was activated by a vibration
      probe. The fingertip model is composed of skin, subcutaneous tissue, bone, and
      nail. The soft tissues (i.e., skin and subcutaneous tissues) were assumed to be
      non-linearly elastic and linearly viscoelastic. The FE model was applied to
      predict the effects of pre-indentation of the vibration probe onto the fingerpad,
      the damping of the soft tissues, and probe mass on the magnitude and phase angle
      of the mechanical impedance and the apparent mass, as measured in the vibration
      tests. The model predictions showed that the probe mass has non-negligible
      effects on the measured biodynamic responses in the vibration tests. In order to
      determine "true" biodynamic responses of the finger-hand-arm system, the mass
      effects have to be cancelled using an appropriate approach. The present analysis
      provided a theoretical explanation, from a biomechanical point-of-view, for the
      inconsistencies in the published experimental data for the biodynamic responses
      of fingerpad.

PMID- 16426888
TI  - Increasing hepatitis C virus-associated hepatocellular carcinoma mortality and
      aging: Long term trends in Japan.
AB  - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in Japan has been
      increasing. The aim of the study was to determine the epidemiological trends in
      HCC mortality in Japan. METHODS: We reviewed the medical records of all patients
      whose death was caused by liver disease between 1981 and 2000 at two hospitals.
      The courses of death were separated based on presence or absence of HCC when
      death ensued. Additionally, cohorts of patients with HCC were analyzed in 5-year
      time periods. RESULTS: The number of deaths from hepatitis C virus (HCV)
      associated HCC steadily increased 2.6 times from 49 to 128 during observation
      period. The mean age at death from HCV-associated HCC from 1996 to 2000 was
      significantly higher than that in the period from 1981 to 1985 (p<0.0001).
      INTERPRETATION: Deaths from HCV-associated HCC increased from 1981 to 2000,
      consistent with the aging of the population in Japan.

PMID- 16426885
TI  - Molecular cloning and characterization of crustacean type-one dopamine receptors:
      D1alphaPan and D1betaPan.
AB  - Dopamine (DA) differentially modulates identified neurons in the crustacean
      stomatogastric nervous system (STNS). While the electrophysiological actions of
      DA have been well characterized, little is known about the dopaminergic
      transduction cascades operating in this system. As a first step toward
      illuminating the molecular underpinnings of dopaminergic signal transduction in
      the crustacean STNS, we have cloned and characterized two type-one DA receptors
      (DARs) from the spiny lobster (Panulirus interruptus): D(1alphaPan) and
      D(1betaPan). We found that the structure and function of these arthropod DARs are
      well conserved across species. Using a heterologous expression system, we
      determined that DA, but not serotonin, octopamine, tyramine or histamine
      activates these receptors. When stably expressed in HEK cells, the D(1alphaPan)
      receptor couples with Gs, and DA elicits an increase in [cAMP]. The D(1betaPan)
      receptor responds to DA with a net increase in [cAMP] that is mediated by Gs and
      Gz.

PMID- 16426887
TI  - Evaluation of new 2,2'-dimethyl-5,5'-dipropoxybenzidine- and 3,3'
      dipropoxybenzidine-based direct dye analogs for mutagenic activity by use of the
      Salmonella/mammalian mutagenicity assay.
AB  - As part of a continuing study aimed at establishing structure-activity
      relationships and heuristic principles useful for the design of non-genotoxic azo
      dyes, a series of new direct dyes based on two non-mutagenic benzidine analogs,
      2,2'-dimethyl-5,5'-dipropoxybenzidine and 3,3'-dipropoxybenzidine, were evaluated
      for mutagenic activity in Salmonella typhimurium strains TA98 and TA100. These
      strains are widely used for mutagenicity screening and have been shown to detect
      the mutagenic activity of benzidine analogs. While some toxicity was seen with
      some dyes at high doses, all of the dyes examined were judged non-mutagenic with
      and without metabolic activation in the standard Salmonella plate-incorporation
      assay. The results in the standard test are consistent with the properties of the
      diamines themselves. However, only one of the dyes was non-mutagenic when a
      reductive-metabolism pre-incubation assay was used. The results of this study
      suggest that although benzidine analogs are potential replacements for benzidine,
      there is a need to understand which mutagenic products are produced when
      reductive metabolism is present. There is also a need to know whether or not
      metal complexes of these dyes are mutagenic. Such information will allow the
      development of new non-mutagenic azo dyes.

PMID- 16426889
TI  - Commercial enzyme immunoassay adapted for the detection of antibodies to
      hepatitis C virus in dried blood spots.
AB  - BACKGROUND: Dried blood spots (DBS) provide a convenient method for blood sample
      collection in many settings where the prevalence of infection with hepatitis C
      virus (HCV) is increasing. Consequently, HCV assays are required that produce
      reliable results using samples derived from DBS. OBJECTIVES AND STUDY DESIGN: The
      optimum buffer for the elution of samples from DBS was selected and the
      performance of a commercial enzyme immunoassay (EIA) was evaluated using these
      DBS eluates and paired plasma samples. RESULTS: DBS with paired plasma samples
      were compared using this modified commercial EIA, which was found to have an
      estimated sensitivity and specificity of approximately 100% for detecting anti
      HCV antibodies in DBS. CONCLUSION: A DBS-based assay for the detection of
      antibodies to HCV will prove valuable for collecting epidemiological data in the
      field or in under resourced settings.

PMID- 16426891
TI  - P300 development during adolescence: effects of DRD2 genotype.
AB  - OBJECTIVE: Young boys at high risk for alcoholism by having a family history of
      alcoholism (FH+) have lower amplitude of the visual P300 event-related scalp
      potential. They have also been reported to have a slowing in the rate of P300
      amplitude change during adolescence. The present study examined whether the
      change in P300 amplitude during adolescence in sons of alcoholics and
      nonalcoholics is affected by D2 dopamine receptor (DRD2) polymorphism. METHODS:
      P300 was elicited with a visual discrimination task from 71 adolescent sons of
      alcoholics and social drinkers (Time 1, T1). The task was readministered 2 years
      later (Time 2, T2). Comparisons were made between boys who had the DRD2 A1 allele
      (A1+) and boys who did not (A1-), and between boys with one or both parents being
      alcoholic (FH+) and boys having no alcoholic parents (FH-). RESULTS:
      Discrimination task accuracy was lowest in the highest risk group (A1+, FH+) at
      T1, and highest in the lowest risk group (A1-, FH-) at T2, producing a
      significant interaction of allelic group x family history group x session.
      Reaction time was faster at T2 than T1, and this effect was larger in FH-boys
      (125 ms) than FH+boys (40 ms). Overall, the behavioral results suggest mild
      performance deficits on the discrimination task are associated with higher risk
      for alcoholism. In both testing sessions, P300 attained larger amplitudes in sons
      of nonalcoholics than sons of alcoholics. At T2 compared to T1, both the latency
      and amplitude of the P300 were decreased. However, while the developmental P300
      latency effect was equivalent in both the A1+ and A1- allelic groups, the P300
      amplitude reduction during adolescence, measured both in response to targets and
      in target minus non-target subtraction waveforms, was only found in boys with the
      A1- allele. CONCLUSION: Differences in the developmental course of P300 amplitude
      over the course of adolescence are dependent on DRD2 polymorphism. SIGNIFICANCE:
      These results suggest the importance of genetic determinants of the dopaminergic
      system in understanding the P300 as a risk marker for substance abuse using an
      integrative developmental perspective.

PMID- 16426890
TI  - Alterations in cerebral perfusion in posttraumatic stress disorder patients
      without re-exposure to accident-related stimuli.
AB  - Functional neuroimaging studies have shown abnormalities of limbic regions in
      patients with posttraumatic stress disorder (PTSD) during symptom provocation and
      cognitive activation. OBJECTIVE: The aim of this study was to determine whether
      PTSD patients without re-exposure to accident-related stimuli would exhibit
      alterations in cerebral perfusion compared with age-matched normal subjects.
      METHODS: Brain perfusion SPECT was measured in medication-free 23 PTSD patients
      and 64 age-matched healthy subjects under resting conditions and analyzed using
      statistical parametric mapping to compare between the patient and control groups.
      RESULTS: We found that PTSD patients exhibited increased cerebral blood perfusion
      in limbic regions and decreased perfusion in the superior frontal gyrus and
      parietal and temporal regions in comparison with those of the normal controls.
      CONCLUSIONS: This result indicates that PTSD patients have alterations in
      cerebral perfusion of limbic regions and the frontal and temporal cortex without
      re-exposure to accident-related stimuli. SIGNIFICANCE: This finding supports the
      hypothesis of the involvement of limbic regions, which might be associated with
      the regulation of emotion and memory, in the pathophysiology of PTSD.

PMID- 16426892
TI  - Newborns discriminate novel from harmonic sounds: a study using
      magnetoencephalography.
AB  - OBJECTIVE: We investigated whether newborns respond differently to novel and
      deviant sounds during quiet sleep. METHODS: Twelve healthy neonates were
      presented with a three-stimulus oddball paradigm, consisting of frequent standard
      (76%), infrequent deviant (12%), and infrequent novel stimuli (12%). The
      standards and deviants were counterbalanced between the newborns and consisted of
      500 and 750 Hz tones with two upper harmonics. The novel stimuli contained
      animal, human, and mechanical sounds. All stimuli had a duration of 300 ms and
      the stimulus onset asynchrony was 1s. Evoked magnetic responses during quiet
      sleep were recorded and averaged offline. RESULTS: Two deflections peaking at 345
      and 615 ms after stimulus onset were observed in the evoked responses of most of
      the newborns. The first deflection was larger to novel and deviant stimuli than
      to the standard and, furthermore, larger to novel than to deviant stimuli. The
      second deflection was larger to novel and deviant stimuli than to standards, but
      did not differ between the novels and deviants. CONCLUSIONS: The two deflections
      found in the present study reflect different mechanisms of auditory change
      detection and discriminative processes. SIGNIFICANCE: The early brain indicators
      of novelty detection may be crucial in assessing the normal and abnormal cortical
      function in newborns. Further, studying evoked magnetic fields to complex
      auditory stimulation in healthy newborns is needed for studying the newborns at
      risk for cognitive or language problems.

PMID- 16426893
TI  - Biological activities on T lymphocytes of a baculovirus-expressed chimeric
      recombinant IgG1 antibody with specificity for the CDR3-like loop on the D1
      domain of the CD4 molecule.
AB  - A baculovirus-expressed chimeric recombinant IgG1 (rIgG1) antibody, with Cgamma1
      and Ckappa human constant domains, was derived from the murine monoclonal
      antibody (mAb) 13B8.2, which is specific for the CDR3-like loop of the CD4
      molecule and which inhibits HIV-1 replication. Chimeric rIgG1 antibody 13B8.2
      blocked, in a dose-dependent manner, antigen presentation through inhibition of
      subsequent IL-2 secretion by stimulated T cells. The one-way mixed lymphocyte
      reaction was abrogated by previous addition of baculovirus-produced rIgG1 13B8.2
      in the T-cell culture. Anti-proliferative activity of rIgG1 was demonstrated on
      CD3-activated CD4+ T lymphocytes from healthy donors, such effect being
      associated with reduced IL-2 secretion of activated T cells. On the other hand,
      no proliferation inhibition was observed on CD4+ T lymphocytes activated with
      phorbol ester plus ionomycin, suggesting that rIgG1 13B8.2 preferentially acts on
      a proximal TCR-induced signaling pathway. Treatment of DBA1/J human CD4
      transgenic mice with 100 microg of recombinant antibody for three consecutive
      days led to in vivo recovery of rIgG1 antibody 13B8.2 both coated on murine T
      lymphocytes and free in mouse serum, without CD4 depletion or down-modulation.
      These findings predict that the baculovirus-expressed chimeric rIgG1 anti-CD4
      antibody 13B8.2 is a promising candidate for immunotherapy.

PMID- 16426894
TI  - Distinct patterns of regeneration of central memory, effector memory and effector
      TCD8+ cell subsets after different hematopoietic cell transplant types: possible
      influence in the recovery of anti-cytomegalovirus immune response and risk for
      its reactivation.
AB  - TCD8+ cells may be divided into subsets with different phenotypes and functions:
      naive, central memory, effector memory and effector. Aiming to better understand
      the differences in early reconstitution of these TCD8+ cell subsets and their
      relationship with post-transplant anti-cytomegalovirus (CMV) immune responses
      recovery, we prospectively analyzed the transfer and expansion of these subsets
      in different transplant types. We found that graft cells from donor's peripheral
      blood, either allogeneic or autologous, were enriched for central memory,
      effector memory and effector phenotypes compared to allogeneic bone marrow
      grafts, as assessed by surface markers phenotyping and granzyme B expression.
      However, post-transplant, these subsets expanded in autologous recipients only,
      reaching numbers much greater than in allo-recipients at days +29 and +96. At the
      same time, autologous recipients presented less CMV reactivation and more
      vigorous CMV-induced interferon-gamma and lymphoproliferative responses. The
      marked loss of allo-transferred memory TCD8+ cells was probably due to the fact
      that they were more activated and more prone to apoptosis than auto-transferred
      TCD8+ cells as assessed by CD69 and active caspase 3 expression. Thus, transfer
      of peripheral blood stem cells in the allogeneic but not autologous setting is
      associated with poor expansion of memory TCD8+ cells, probably delaying antiviral
      immune reconstitution. These data may have important implications for the design
      of better strategies to immunoprotect this population against infectious
      challenges since different transplant types have different potentials for memory
      TCD8+ cells transfer and expansion.

PMID- 16426895
TI  - Hysteroscopic surgery.
AB  - Hysteroscopy and visually directed endometrial sampling have replaced blind
      curettage for the diagnosis of endometrial disease. Hysteroscopy can be used to
      detect endometrial cancer and various premalignant lesions, as well as to
      diagnose intrauterine polyps and submucous fibroids. It can also be used to
      locate lost intrauterine devices, assess the shape and size of the endometrial
      cavity during an infertility work-up and to visualise intrauterine septae and
      adhesions. If the hysteroscopist possesses special skills and training, it can be
      used to perform intrauterine sterilisation by occluding the tubal ostia. The
      ability to perform endometrial ablation as an alternative to hysterectomy in
      patients with menorrhagia has led to reduction in the number of hysterectomies
      performed. Long-term follow-up has confirmed the success of this procedure, but
      it is not without complications. The inherent dangers and complications of
      endometrial ablation and the considerable skill and training it requires has led
      to the development of numerous second-generation devices, which can involve
      balloons that are heated with circulating fluid, impedance-controlled endometrial
      ablation or surface electrodes, heated fluid running through the hysteroscope
      under direct vision or the use of microwaves or cryotherapy. This chapter reviews
      the techniques, potential complications and evidence for the effectiveness of the
      common diagnostic and therapeutic hysteroscopic procedures.

PMID- 16426896
TI  - In vivo effects of myeloablative alkylator therapy on survival and
      differentiation of MGMTP140K-transduced human G-CSF-mobilized peripheral blood
      cells.
AB  - High-intensity alkylator-based chemotherapy is required to eradicate tumors
      expressing high levels of O6-methylguanine DNA methyltransferase (MGMT). This
      treatment, however, can lead to life-threatening myelosuppression. We
      investigated a gene therapy strategy to protect human granulocyte colony
      stimulating factor-mobilized peripheral blood CD34+ cells (MPB) from a high
      intensity alkylator-based regimen. We transduced MPB with an oncoretroviral
      vector that coexpresses MGMT(P140K) and the enhanced green fluorescent protein
      (EGFP) (n = 5 donors). At 4 weeks posttransplantation into nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice, cohorts were not
      treated or were treated with low- or high-intensity alkylating chemotherapy. In
      the high-intensity-treated cohort, it was necessary to infuse NOD/SCID bone
      marrow (BM) to alleviate hematopoietic toxicity. At 8 weeks posttreatment, human
      CD45+ cells in the BM of mice treated with either regimen were EGFP+ and
      contained MGMT-specific DNA repair activity. In cohorts receiving low-intensity
      therapy, both primitive and mature hematopoietic cells were present in the BM.
      Although B-lymphoid and myeloid cells were resistant to in vivo drug treatment in
      cohorts that received high-intensity therapy, no human CD34+ cells or B-cell
      precursors were detected. These data suggest that improved strategies to optimize
      repair of DNA damage in primitive human hematopoietic cells are needed when using
      high-intensity anti-cancer therapy.

PMID- 16426897
TI  - Differential effects of post-natal development, animal strain and long term
      recovery on the restoration of neuromuscular function after neuromyotoxic injury
      in rat.
AB  - We have analysed the effect of long term recovery, post-natal development and
      animal strain on the extent of restoration of neuromuscular function after
      neuromyotoxic injury in the rat (Rattus norvegicus). Muscle isometric contractile
      properties of soleus muscle in response to nerve stimulation were measured in
      situ in snake venom injured muscles and compared to contralateral uninjured
      muscles. We show here that neuromuscular function was not fully recovered until
      24 weeks after injury in young adult (2-3 month old) Wistar rats. Moreover, the
      level of functional recovery 3 weeks after injury induced in juvenile rats (1
      month old) was not globally different from that in younger adult, adult (10 month
      old) and older adult (24 month old) Wistar rats. Furthermore, the level of
      recovery of some contractile parameters differed between Wistar and Sprague
      Dawley strains 3 weeks after injury. In conclusion, a very long time (>12 weeks)
      is required for full neuromuscular recovery following neuromyotoxic injury of
      young adult rats. Moreover, neuromuscular recovery during post-natal development
      is not markedly different from that during adult stage in the Wistar rat strain.
      Finally, some rat strain differences are observed in the recovery after injury of
      young adult rats.

PMID- 16426898
TI  - Temperature increase results in oxidative stress in goldfish tissues. 2.
      Antioxidant and associated enzymes.
AB  - Activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx),
      glutathione-S-transferase (GST), glutathione reductase (GR), and glucose-6
      phophate dehydrogenase (G6PDH) were measured in four tissues of goldfish,
      Carassius auratus L., over 1-12 h of high temperature (35 degrees C) exposure
      followed by 4 or 24 h of lower temperature (21 degrees C) recovery. SOD activity
      was strongly affected by heat shock, increasing 4-fold in brain, liver, and
      kidney, but was mainly reversed at recovery. In some tissues, activities of SOD,
      catalase, GPx, and G6PDH decreased significantly after 1 h heat shock exposure
      suggesting that thermal inactivation possibly occurred, but were renewed at
      further exposure. In many cases, 4 h of return to the initial temperature
      decreased enzyme activities. High correlation coefficients between SOD activities
      and levels of lipid peroxidation products suggest that these products might be
      involved in up-regulation of antioxidant defense. Several enzymes (SOD, GST, GR)
      responded to stress in coordinated manner.

PMID- 16426899
TI  - A likelihood approach to analyzing clinical trial data when treatments favor
      different outcomes.
AB  - It is increasingly common in clinical trials to design studies for which more
      than one primary outcome exists. Methods that exist for more than one outcome are
      generally concerned with identifying one of two situations: (1) improvement in
      all outcomes from one treatment, as compared to the other treatment(s); or (2)
      improvement in a single efficacy endpoint, without an excess of toxicity. In
      contrast, the Colpopexy and Urinary Reduction Effort (CARE) Study is a randomized
      clinical trial comparing two treatments that presents a slightly different
      scenario. In this study, there are two outcomes, and it was anticipated by the
      investigators that each treatment may favor a different outcome. Few statistical
      methods exist to address the specific challenges encountered by this design. We
      designed a method to address the specific analytic issues raised in the planning
      of the CARE study. We developed a likelihood ratio approach to test whether or
      not a treatment difference exists at the end of the study by considering both the
      absolute treatment differences and the direction of the differences with respect
      to the treatments. This method involves simultaneously testing each component of
      a composite null hypothesis, while maintaining an overall type I error rate. A
      simulation study is performed to evaluate the operating characteristics of this
      test, in which we find that our joint likelihood-ratio test has a power as high
      as, or higher than, other commonly used methods for multiple outcomes, while
      maintaining a nominal type I error rate.

PMID- 16426900
TI  - Statistical evaluation of HIV vaccines in early clinical trials.
AB  - The HIV pandemic is a pressing threat to global public health; HIV vaccine
      development is critical. Clinical evaluation of HIV vaccine candidates differs
      from the standard therapeutics trial framework primarily due to the fact that
      healthy individuals are studied. We present an early stage evaluation program
      developed for the HIV Vaccine Trials Network (HVTN) motivated by characteristics
      unique to the vaccine setting. The program consists of 3 prototypical stages
      (Phase I, Ib, II) that provide a unified yet flexible approach to the safety and
      immunogenicity evaluation of diverse vaccine regimens. The goal of these early
      trials is to narrow the number of candidate vaccines to the most promising
      candidates worthy of further study in efficacy trials.

PMID- 16426901
TI  - Differing influence of sympathectomy on smooth muscle cells and fibroblasts in
      cerebral and peripheral muscular arteries.
AB  - In the present study, we examined the effect of sympathectomy on the distribution
      and the relative expression of cytoskeletal proteins used as markers of
      phenotypic modulation of vascular smooth muscle cells (SMCs) and myofibroblasts
      (MFBs) in rabbit femoral (FA) and basilar (BA) arteries. Adult rabbits were
      treated either with repeated 6-hydroxydopamine (6-OHDA) for sympathectomy or with
      vehicle for control. Cross sections taken from sympathectomized and control
      arteries 79 days later were immunolabelled for vimentin, desmin, alpha-smooth
      muscle actin (alpha-SM actin), beta-isoform of actin and h-caldesmon. The
      distribution of these proteins and the intensity of fluorescent labelled SMCs
      were examined under a confocal microscope. In the sympathectomized BA, there was
      no change for desmin, vimentin and h-caldesmon expression, but the expression of
      both alpha-SM actin and the beta-isoform was significantly higher (+19% and +30%,
      respectively). In the sympathectomized FA, the expression of the alpha- and beta
      isoforms of actin remained unchanged, whereas those of desmin and vimentin were
      significantly higher (+35% and 17%, respectively) and h-caldesmon expression was
      lowered by 13%. In contrast to intact FAs, the external layers of
      sympathectomized FAs revealed migration of fibroblasts from the adventitia and
      death of SMCs. These results strongly suggest that sympathetic nerves intervene
      in the cytoskeletal protein remodelling through phenotypic modulation of both
      SMCs and MFBs during post-natal development, and in pathologies involving similar
      phenomena, such as atherosclerosis.

PMID- 16426902
TI  - Identification and developmental expression analysis of a novel homeobox gene
      closely linked to the mouse Twirler mutation.
AB  - The Twirler mutation arose spontaneously and causes inner ear defects in
      heterozygous and cleft lip and/or cleft palate in homozygous mutant mice,
      providing a unique animal model for investigating the molecular mechanisms of
      inner ear and craniofacial development. Here, we report the identification of a
      novel homeobox gene, Iroquois-related homeobox like-1 (Irxl1), from the Twirler
      locus. Irxl1 encodes a TALE-family homeodomain protein with its homeodomain
      exhibiting the highest amino acid sequence identity (54%) to those of
      invertebrate Iroquois and vertebrate Irx subfamily members. The putative Irxl1
      protein lacks the Iro-box, a conserved motif in all known members of the Irx
      subfamily. Searching the databases showed that Irxl1 orthologs exist in Xenopus,
      chick, and mammals. In situ hybridization analyses of mouse embryos at various
      developmental stages showed that Irxl1 mRNA is highly expressed in the
      frontonasal process and palatal mesenchyme during primary and secondary palate
      development. In addition, Irxl1 mRNA is strongly expressed in mesenchyme
      surrounding the developing inner ear, in discrete regions of the developing
      mandible, in the dermamyotome during somite differentiation, and in a subset of
      muscular structures in late embryonic stages. The developmental expression
      pattern indicates that Irxl1 is a good candidate gene for the Twirler gene.

PMID- 16426903
TI  - Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients
      with ICF syndrome without downstream kinase activity.
AB  - Double strand DNA breaks in the genome lead to the activation of the ataxia
      telangiectasia mutated (ATM) kinase in a process that requires ATM
      autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is
      previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins
      involved in arresting the cell cycle, including p53, and in repairing the DNA
      breaks. Chloroquine treatment and other manipulations that produce chromatin
      defects in the absence of detectable double strand breaks also trigger ATM
      phosphorylation and the phosphorylation of p53 in primary human fibroblasts,
      while other downstream substrates of ATM that are involved in the repair of DNA
      double strand breaks remain unphosphorylated. This raises the issue of whether
      ATM is constitutively activated in patients with genetic diseases that display
      chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from
      patients with different types of chromatin disorders: Immunodeficiency,
      Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome,
      Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show
      that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but
      not from the other syndromes. The phosphorylated ATM in ICF cells did not
      phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require
      the presence of double strand breaks. We demonstrate that ICF cells respond
      normally to ionizing radiation, ruling out the possibility that genetic
      deficiency in ICF cells renders activated ATM incapable of phosphorylating its
      downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells
      or in chloroquine-treated wild type LCLs. In this regard the response to
      chromatin-altering agents differs between primary fibroblasts and LCLs. Our
      findings indicate that although phosphorylation at serine-1981 is essential in
      the activation of the ATM kinase, serine-1981 phosphorylation is insufficient to
      render ATM an active kinase towards downstream substrates, including p53.

PMID- 16426904
TI  - Pulmonary infection in mild variant cystic fibrosis: implications for care.
AB  - BACKGROUND: Disease phenotype in cystic fibrosis (CF) shows considerable
      heterogeneity. Atypical or mild mutations in the CFTR gene have been linked to
      late-onset pulmonary disease; however, few reports document the condition of the
      airway in infants and young children with apparent "mild" disease. Prognosis is
      uncertain in this group of patients and this, in turn, has led to inconsistency
      in management. Our initial experience of pulmonary infection in children with
      mild variant CF prompted a more detailed review of clinical outcome. METHODS: A
      retrospective cohort study was carried out comparing frequency of bacterial
      isolates and clinical outcomes in eleven compound heterozygotes for DeltaF508 and
      a second mild mutation, mainly R117H, with a matched group of DeltaF508
      homozygotes. RESULTS: Staphylococcus aureus was isolated in 8 of the 11 patients
      with mild variant disease and Pseudomonas aeruginosa found in 7 (64%), although
      the frequency of positive cultures was significantly less (2.8/year) than the
      DeltaF508 homozygotes (6.1/year, p<0.05). Shwachman scores (median+range) were
      significantly higher in patients with mild mutations - 94, 74-92 vs. 88, 77-91;
      p<0.005); there was also a small but significant difference in chest radiograph
      (Chrispin-Norman) scores (median+range) (mild 5.1, 4-9, vs. severe 5.8, 3-10; p
      0.04). There was little difference in lung function in terms of FEV1
      (median+range) between the two groups (% predicted, mild 86.5, 68-87 vs. severe
      76.0, 65-88; p 0.5). CONCLUSIONS: Most patients with mild variant CF will have
      bacterial isolates from airway cultures requiring antibiotic therapy three to
      four times a year. Infection with both S. aureus and P. aeruginosa is common.
      Anti-staphylococcal prophylaxis for the first two years should be considered.

PMID- 16426905
TI  - Rapid determination of valsartan in human plasma by protein precipitation and
      high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method for the determination of
      valsartan in human plasma is reported. The assay is based on protein
      precipitation with methanol and reversed-phase chromatography with fluorimetric
      detection. The preparation of a batch of 24 samples takes 20 min. The liquid
      chromatography was performed on an octadecylsilica column (50 mm x 4 mm, 5 microm
      particles), the mobile phase consisted of acetonitrile -15 mM dihydrogenpotassium
      phosphate, pH 2.0 (45:55, v/v). The run time was 2.8 min. The fluorimetric
      detector was operated at 234/374 nm (excitation/emission wavelength). The limit
      of quantitation was 98 ng/ml using 0.2 ml of plasma. Within-day and between-day
      precision expressed by relative standard deviation was less than 5% and
      inaccuracy did not exceed 8%. The assay was applied to the analysis of samples
      from a pharmacokinetic study.

PMID- 16426906
TI  - Fluorescence properties and conformational stability of the beta-hemocyanin of
      Helix pomatia.
AB  - The beta-hemocyanin (beta-HpH) is one of the three dioxygen-binding proteins
      found freely dissolved in the hemolymph of the gastropodan mollusc Helix pomatia.
      The didecameric molecule (molecular mass 9 MDa) is built up of only one type of
      subunits. The fluorescence properties of the oxygenated and apo-form (copper
      deprived) of the didecamer and its subunits were characterized. Upon excitation
      of the hemocyanins at 295 or 280 nm, tryptophyl residues buried in the
      hydrophobic interior of the protein determine the fluorescence emission. This is
      confirmed by quenching experiments with acrylamide, cesium chloride and potassium
      iodide. The copper-dioxygen system at the binuclear active site quenches the
      tryptophan emission of the oxy-beta-HpH. The removal of this system increases the
      fluorescence quantum yield and causes structural rearrangement of the
      microenvironment of the emitting tryptophyl residues in the apo-form. Time
      resolved fluorescence measurements show that the oxygenated and copper-deprived
      forms of the beta-HpH and its subunits exist in different conformations. The
      thermal stability of the oxy- and apo-beta-HpH is characterized by a transition
      temperature (Tm) of 84 degrees C and 63 degrees C, respectively, obtained by
      differential scanning calorimetry. Increase of the temperature influences the
      active site at lower temperatures than the environments of tryptophans and
      tyrosines causing a loss of oxygen bound to the copper atoms. This process is, at
      least partially, reversible as after cooling of the protein samples, around 60%
      reinstatement of the copper-peroxide band has been observed. The results confirm
      the role of the copper-dioxygen complex for the stabilization of the hemocyanin
      structure in solution. The other important stabilizing factor is oligomerization
      of the hemocyanin molecule.

PMID- 16426911
TI  - Microsatellite analysis of the APC gene and immunoexpression of E-cadherin,
      catenin, and tubulin in esophageal squamous cell carcinoma.
AB  - The histological features that accompany the development and progression of solid
      tumors are known to be controlled by a distinct cascade of molecular events. One
      such event is the inactivation of tumor suppressor genes, such as the adenomatous
      polyposis coli (APC) gene. Disruption of the cadherin-catenin cell adhesion
      complex also plays a role in the initial steps of cancer invasion and metastasis
      whereas alterations in cell structural molecules, such as tubulin, may contribute
      to the cancer phenotype. The understanding of the status of these molecules in
      ESSC may provide novel markers that could impact on management of the disease.
      The present study examined alterations in the microsatellite sequence of the APC
      gene via fluorescent-based polymerase chain reaction in 100 cases of primary
      esophageal squamous cell carcinoma. In addition, the expression of E-cadherin,
      alpha- and beta-catenin, and alpha- and beta-tubulin was analyzed using
      immunohistochemistry. These data were then statistically compared with each other
      as well as the relevant clinicopathologic data. Although the APC markers (D5S210,
      D5S346, D5S299, and D5S82) tested did show an overall high frequency of allelic
      imbalance/loss of heterozygosity (62.48%) and microsatellite instability
      (41.27%), they did not show prognostic significance in the study cohort and were
      not correlated with the immunohistochemical data. The tubulin proteins showed no
      significant change in expression in the tumor tissue The decreased
      immunoreactivity of E-cadherin was statistically correlated with the presence of
      lymph node metastases (P = .0180). Although alpha- and beta-catenin as well as E
      cadherin showed no direct prognostic value, E-cadherin may warrant further
      investigation as an indirect prognostic indicator by allowing more accurate
      prediction of lymph node metastases.

PMID- 16426912
TI  - Quantitative determination of human telomerase reverse transcriptase messenger
      RNA expression in premalignant cervical lesions and correlation with human
      papillomavirus load.
AB  - Expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA)
      and human papillomavirus (HPV)-16 load were quantified using real-time polymerase
      chain reaction and correlated with cytological findings and the presence of HPV
      infection in cervical specimens. Human telomerase reverse transcriptase mRNA
      expression was evaluated in 15 (20.5%) of 73 specimens of atypical squamous
      epithelial cells of undetermined significance, in 62 (39.7%) of 156 low-grade
      squamous intraepithelial lesions (LGSILs), in 49 (96%) of 51 high-grade squamous
      intraepithelial lesions (HGSILs), and in 9 (20%) of 45 normal samples, whereas
      viral load was quantified in 52 (89.6%) of 58 samples infected with HPV-16. The
      mean levels of hTERT mRNA expression were 0.11 in normal tissue, 0.23 in atypical
      squamous epithelial cells of undetermined significance, 0.75 in LGSILs, and 2.5
      in HGSILs. Thus, a significant increase in hTERT mRNA expression was observed
      with increasing degrees of cervical dysplasia. The HPV-16 load was significantly
      higher in samples of HGSIL than in those of LGSILs (P < .001). A significant
      correlation was observed between viral load and quantitative hTERT mRNA
      expression (r = 0.65; P < .05). Quantitative hTERT mRNA assessment showed 96%
      sensitivity and 100% negative predictive value for high-grade dysplasia, whereas
      the specificity and positive predictive value were 72% and 36.2%, respectively.
      It is suggested that quantitative hTERT has a very high sensitivity and negative
      predictive value, whereas the observed specificity was moderate, indicating that
      it cannot be used as a diagnostic marker but may be an adjunct in the management
      of women with high-grade cervical dysplasia. However, the final diagnosis must
      rely on the inclusion of clinical evaluation and additional assessment data.

PMID- 16426913
TI  - Improved clonality analysis of multifocal bladder tumors by combination of
      histopathologic organ mapping, loss of heterozygosity, fluorescence in situ
      hybridization, and p53 analyses.
AB  - The clonality status of multifocal bladder tumors is still controversially
      discussed with experimental evidence for both monoclonality and field
      cancerization. Methodologically, loss of heterozygosity (LOH) and genomic
      sequencing analyses are widely used in clonality analysis of malignant tumors. In
      the present study, we used LOH analysis and genomic sequencing in combination
      with fluorescence in situ hybridization (FISH) and extensive histopathologic
      whole-organ mapping to determine the clonal relationship of multifocal bladder
      cancer disease. Tissue sections (1 cm(2)) covering the entire urothelial lining
      were systematically dissected from 2 cystectomy specimens (cystectomy 1, no
      urothelial lesions, bladder infiltration by a leiomyosarcoma of the vaginal wall;
      cystectomy 2, multifocal pT3G3 tumors). The location of each sample was
      documented (bladder mapping). Urothelial cells were microdissected for LOH
      (chromosomes 9, 17p) and FISH analysis (CDKI2 (9p21), FACC (9q22), p53 (17p13.1),
      and centromeric probes for corresponding chromosome). Exons 5 to 9 of the p53
      gene were sequenced in all tumor samples. No chromosomal alterations were
      detected in the cystectomy specimen without urothelial malignancies. The tumor
      bearing bladder showed an increasing frequency of deletions with increasing
      malignancy of the investigated lesions. LOH analysis detected deletions only on
      chromosomes 9p and 17p. In contrast, FISH analysis revealed deletions of all
      investigated genes at chromosomes 9p, 9q, and 17p in all samples analyzed
      (preneoplastic and neoplastic tissue). An identical p53 mutation in codon 281 was
      found in all 7 analyzable tumor samples. Combination of molecular data with
      histopathologic bladder mapping suggested a monoclonal development of the
      multifocal lesions mostly via intraurothelial migration. Our data strengthen the
      results from recently published studies that patients with advanced urothelial
      carcinoma seem to have a monoclonal panurothelial disease in most cases. FISH
      showed a much higher sensitivity for detection of chromosomal losses than
      classical LOH analysis, especially in preneoplastic and small lesions. Combining
      3 molecular approaches together with histopathologic organ mapping presents a
      valuable tool to determine the clonality status of multifocal bladder tumors.

PMID- 16426915
TI  - Prognostic value of mucins in the classification of ampullary carcinomas.
AB  - The ampulla of Vater is of high clinical relevance with regard to influx of
      chyme, ascending inflammation, intubation during diagnostic and therapeutic
      endoscopic investigation, therapeutic papillotomy, and especially to malignant
      transformation. Little is known about the distribution of mucins in the ampulla.
      In this study, we have investigated the mucin distribution in the normal ampulla
      of Vater and compared it to duodenal mucosa and Brunner glands. Expression of
      mucins in the ampulla of Vater and duodenum was monitored by reverse
      transcription-polymerase chain reaction and localization of the products by
      immunohistochemistry. The samples investigated originated from 30 autopsy cases.
      Mucins MUC1, MUC3, MUC4, MUC5AC, MUC5B, MUC6, MUC7, and MUC8 were expressed in
      the ampulla of Vater. Immunohistochemistry revealed production of MUC4, MUC5AC,
      MUC5B, and MUC6. The mucin composition varied in comparison with the duodenum
      referring to MUC2, MUC7, and MUC8. Detected mucins contribute to innate immunity,
      epithelial restitution, and protection against the aggressive secretions of the
      liver, gall bladder, and pancreas. By cross-linking, they influence the
      rheological properties of the secretions in the ampulla and facilitate
      unidirectional flow into the duodenum. Knowledge of their pattern of expression
      has prognostic value with regard to the detection of malignancy. The observed
      differences in the mucin distribution between the duodenum and the ampulla of
      Vater support the use of MUC2, MUC7, and MUC8 as useful tool in the
      classification of ampullary carcinomas.

PMID- 16426914
TI  - The proliferation center microenvironment and prognostic markers in chronic
      lymphocytic leukemia/small lymphocytic lymphoma.
AB  - Prognostication in chronic lymphocytic leukemia/small lymphocytic lymphoma
      (CLL/SLL) based, in part, on ZAP-70 and CD38 expression, and to a lesser extent,
      on MUM1/IRF4 expression, is currently of great interest. The more aggressive type
      of CLL/SLL is reportedly characterized by neoplastic cells that are more
      responsive to B-cell signaling with proliferation centers (PCs), a potentially
      important site of neoplastic cell stimulation. To study the relationship of these
      markers to each other and to the pattern of PCs, immunohistochemical stains for
      ZAP-70 and MUM1/IRF4 were performed and the PC patterns assessed (where possible)
      in 29 tissue biopsies with CLL/SLL. CD38 expression was assessed in 18 cases
      using flow cytometry. Ten evaluable cases had a typical PC pattern and 16 an
      atypical pattern with larger or more confluent PCs and/or more numerous
      paraimmunoblasts/transformed cells. ZAP-70 was positive in 14 of 28 cases,
      including 3 with atypical PCs and enhanced PC staining. All 29 cases showed
      MUM1/IRF4 expression in PCs. Seven cases, none with atypical PC, also showed
      uniform positivity throughout, 14 showed weaker staining of surrounding
      lymphocytes, and 8 had PC staining only. CD38 was positive in 14 of 18 cases. The
      only significant association identified was between uniform MUM1/IRF4 positivity
      and typical PCs (P = .004). These findings highlight the complex
      interrelationship of prognostic markers in CLL/SLL and demonstrate potentially
      important microenvironmental variations in their expression. They support the
      hypothesis that PCs are a site for B-cell receptor signaling, which helps explain
      reported site-dependent antigenic variation in CLL/SLL, and suggest that PC
      morphology may correlate with other biological features.

PMID- 16426916
TI  - Urothelial carcinoma with rhabdoid features: report of 6 cases.
AB  - Extrarenal rhabdoid tumors have been described in a variety of primary sites with
      only rare case reports of urothelial carcinomas with rhabdoid features in the
      literature. In this report, we describe the clinicopathologic characteristics,
      including clinical follow-up on 6 cases of urothelial carcinoma with prominent
      rhabdoid features. Four cases were retrieved from the consultation files of one
      of the authors and 2 were retrieved from the surgical pathology files at our
      institution. The patients were all men, with ages ranging from 53 to 86 years
      (mean, 66.5 years). Patients initially presented with hematuria or obstructive
      symptoms. The sites included bladder (n = 4) and renal pelvis (n = 2). All cases
      had a prominent rhabdoid component (mean, 60%), ranging from 40% to 80%. In
      addition to the rhabdoid component, multiple coexistent histological components
      were seen, including in situ urothelial carcinoma (carcinoma in situ) and high
      grade papillary urothelial carcinoma (n = 2), poorly differentiated carcinoma
      with small-cell features (n = 1), sarcomatoid (n = 2), and a myxoid component (n
      = 2). All cases in this series had focal or diffuse positive staining with one or
      more cytokeratin markers (epithelial membrane antigen, CAM 5.2, AE1/AE3). Of the
      6 patients, 4 were treated initially with surgery (radical cystoprostatectomy, n
      = 2; radical nephrectomy, n = 2). Of 6 patients, 2 died within 1 month, whereas a
      third patient died within 4 months. The remaining 3 patients were alive at 3, 3,
      and 9 months after diagnosis. The histological and immunohistochemical findings
      in this study serve to broaden the morphological spectrum of urothelial
      carcinomas with prominent rhabdoid features and add further evidence as to their
      poor prognosis.

PMID- 16426917
TI  - Investigation of children for mitochondriopathy confirms need for strict patient
      selection, improved morphological criteria, and better laboratory methods.
AB  - We studied muscle biopsies of 103 pediatric patients in whom clinical suspicion
      for disorder of energy metabolism was highest in 13 patients, intermediate in 8
      patients, and lowest in 82 patients. Electron transport complex (ETC) enzyme
      activity measurements were available in 96 of 103 patients. Most children with
      unclassified encephalopathy before biopsy had negative or equivocal morphological
      and biochemical evaluation for disorder of energy metabolism (72/85). The
      incidence of ETC abnormality and morphological abnormality in muscle from 39
      patients with clinical encephalomyopathy (groups I, II, and III) was 20% and 38%,
      respectively. In 21 children with high or intermediate clinical suspicion of
      mitochondriopathy, light microscopy was confirmative in 12, ultrastructure was
      confirmative in 15, and major ETC abnormality was present in only 4 (29%) of 14.
      In 82 children with lower clinical suspicion of mitochondriopathy, morphological
      criteria at both the light and electron microscopic level were absent, and major
      abnormality of ETC activity was uncommon, in 9 (11%) of 82. Partial reductions of
      ETC activity occurred in 15 (18%) of 82, but are of uncertain significance.
      Ragged blue fibers were more prevalent in infants with mitochondriopathy than
      ragged red fibers. Increase of large, but not small, subsarcolemmal mitochondrial
      aggregates based on succinate dehydrogenase histochemistry is a useful indicator
      for mitochondriopathy. Thus, a distinction should be made between small
      aggregates (normal) and large aggregates. Using strict criteria to define
      pathological mitochondria, we concluded that electron microscopy is a powerful
      tool in the diagnosis of mitochondriopathy mainly when clinical suspicion is
      high. We found no consistent difference in the frequency of mitochondrial
      "proliferation" as currently defined or in citrate synthase activity in any
      group. Better patient selection in infants and children and better methods for
      investigation of mitochondriopathy are needed.

PMID- 16426918
TI  - Mismatch repair genes in renal cortical neoplasms.
AB  - Mutation of human mutL homolog 1 (MLH-1) and human mutS homolog 2 (MSH-2) has
      been linked with the pathogenesis of colorectal carcinoma in hereditary
      nonpolyposis colorectal cancer syndrome and other carcinomas. Mutations of these
      genes in renal cell carcinomas were recently described. The aim of this study was
      to examine the expression of MLH-1 and MSH-2 in renal cortical neoplasms of
      various histological types by immunohistochemistry. Thirty-eight (n = 38)
      resected renal tumors were obtained from the surgical pathology files of the
      UMass Memorial Healthcare, including clear cell carcinomas (CLEARs, n = 20),
      papillary carcinomas (PAPs, n = 8), chromophobe carcinomas (CHRs, n = 4), and
      oncocytomas (ONCs, n = 6). Positive immunostaining for MLH-1 and MSH-2 was graded
      by the number of positive tumor cell nuclei, as follows: 0, negative; 1, up to
      one third of positive nuclei; 2, one to two thirds positive; and 3, greater than
      two thirds positive. Loss of MLH-1 or MSH-2 was defined as a tumor with grade 0
      or 1, compared with the normal tubules. Normal tubules and intercalated ducts
      contained cells positive for MLH-1 and MSH-2 in all cases. For both antibodies,
      positive staining in tumors ranged from grade 1 to 3 in the CLEAR and PAP but was
      only grade 2 to 3 in the CHR and ONC. Loss of MLH-1 and/or MSH-2 occurred in
      malignant tumors but not in ONC. Loss of MLH-1 was present in 8 (40%) of 20
      CLEARs and 4 (50%) of 8 PAPs, compared with loss of MSH-2 in 4 (20%) of 20 CLEARs
      and 1 (25%) of 4 CHRs. Our results suggest that loss of mismatch repair genes is
      involved in the malignant transformation in some renal carcinomas, particularly
      those derived from the proximal tubules.

PMID- 16426919
TI  - The differential expression of VEGF, VEGFR-2, and GLUT-1 proteins in disease
      subtypes of systemic sclerosis.
AB  - Our aim was to evaluate (a) whether there is differential expression of the
      endothelial regulator vascular endothelial growth factor (VEGF), its receptor
      (VEGFR-2), and the hypoxia-associated glucose transporter molecule, GLUT-1, in
      skin biopsies from different disease subtypes of systemic sclerosis (SSc) and (b)
      whether they associate with dermal calcinosis, a significant complication of SSc.
      Skin punch biopsies were taken from the forearms of 66 SSc patients including 18
      with limited cutaneous disease without calcinosis (lcSSc), 23 with calcinosis
      (lcSSc/cal), and 25 with diffuse cutaneous disease (dcSSc) and from 12 healthy
      control subjects. The histological appearance of the skin was graded as G0
      (normal), G1 (dermal edema), or G2 or G3 (increasing fibrotic changes).
      Immunohistochemistry was performed with antibodies to VEGF, VEGFR-2, and GLUT-1.
      Staining was assessed in the epidermis, microvessels, and fibroblasts. The
      Kruskal-Wallis 1-way analysis of variance was used to compare the data between
      disease groups. VEGF protein was located in the epidermis and in dermal
      endothelial cells, pericytes, fibroblasts, and inflammatory cells. In dcSSc only,
      there was a significant increase in VEGF staining intensity in the keratinocytes
      and pericytes and the lowest percentage of microvessels with VEGF-positive
      endothelial cells. GLUT-1 protein was located in the epidermis, erythrocytes, and
      perineurium. In both lcSSc/cal and dcSSC, but not lcSSc, there were significant
      increases in GLUT-1 staining intensity of keratinocytes. We propose that in
      patients with dcSSc, there is a net increase in unbound VEGF in skin that may
      account for the raised levels of VEGF in serum reported by others. Increased GLUT
      1 expression in lcSSc/cal and dcSSc indicates that hypoxia is an associated
      factor.

PMID- 16426920
TI  - The significance of prohibitin and c-Met/hepatocyte growth factor receptor in the
      progression of cervical adenocarcinoma.
AB  - To examine the importance of prohibitin 1 and c-Met/hepatocyte growth factor
      receptor (HGFR) expression in human cervical adenocarcinomas, 85 patients (69
      with invasive adenocarcinoma [ACA] and 16 with adenocarcinoma in situ [AIS]) were
      studied using immunohistochemistry. High prohibitin 1 expression was found in 51
      (73.9%) of the 69 ACAs and 11 (68.7%) of the 16 AIS lesions. Prohibitin 1
      overexpression was significantly higher in ACA and AIS than in adjacent
      nonneoplastic glandular epithelium (P < .001 for both comparisons). Prohibitin 1
      expression was also positively related to tumor size (P = .019) or parametrial
      involvement (P = .027) in ACA. c-Met was expressed in 21 ACAs (30.4%) and was
      positively correlated with the Federation Internationale de Gynecologie et
      d'Obstetrique (International Federation of Gynecology and Obstetrics) stage
      classification (P = .007) or nodal metastasis (P = .047). Nodal metastasis (P =
      .028) and c-Met expression (P = .022) were independent predictors for the overall
      survival of patients in multivariate analysis using the Cox regression method.
      Prohibitin 1 activation seems to be an early event, whereas c-Met overexpression
      may be important for the progression of cervical adenocarcinomas. Evaluation of c
      Met expression status may identify a subset of patients with cervical
      adenocarcinoma who require more intensive treatment.

PMID- 16426921
TI  - C-KIT expression in ductal carcinoma in situ of the breast: co-expression with
      HER-2/neu.
AB  - The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium
      and is decreased in invasive breast cancer. In this study, we analyzed the
      protein expression and the mutational status of c-KIT in ductal carcinoma in situ
      (DCIS) of the breast and correlated these findings with nuclear grade,
      architectural pattern, and expression of HER-2, estrogen receptor (ER)-alpha, and
      progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed
      immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21
      DCIS with concurrent carcinoma). Direct sequencing of exons 9 and 11 of the c-KIT
      gene was performed to analyze the hot spot mutational regions in representative
      cases. C-KIT expression was found in 55 (52.8%) of all DCIS, correlating with
      high nuclear grade (P < .0001), comedonecrosis (P < .0001), and solid growth
      pattern (P = .001). Furthermore, c-KIT expression was strongly associated with
      HER-2 positivity (P < .0001) and was significantly lower in ER- or PR-positive
      cases (P = .001 and P = .006, respectively). C-KIT expression alone or co
      expression with HER-2 in pure DCIS did not differ significantly from DCIS with
      invasive component (P = .09). Mutational analysis in 6 c-KIT-positive DCIS
      revealed no activating mutations in exons 9 or 11. Our findings suggest that the
      expression of c-KIT protein might define a subset of poorly differentiated, HER-2
      positive DCIS with decreased expression of steroid hormone receptors,
      comedonecrosis, and a solid growth pattern. The implications of c-KIT and HER-2
      co-expression for breast carcinogenesis should be further evaluated.

PMID- 16426922
TI  - Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous
      neoplasms of the pancreas: a tissue microarray analysis.
AB  - Abrogation of the Wnt-signaling pathway is implicated in the carcinogenesis of
      several malignancies, especially colorectal cancer where up to 90% of cases are
      thought to have impaired Wnt signaling. It is less frequently involved in
      conventional ductal pancreatic adenocarcinoma. This pathway has not been explored
      in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas previously
      and formed the basis of this study. A tissue microarray of 18 cases of IPMN was
      stained for proteins involved in the Wnt pathway: adenomatous polyposis coli
      (APC), pan-beta-catenin, axin 2, glycogen synthase 3alphabeta and 3beta, c-myc, E
      cadherin, and cyclin D1. The IPMNs were classified as 8 adenomas, 3 borderline,
      and 7 cases with carcinoma in situ and/or invasive carcinoma, occurring in 13
      females, and the overall age range was 45 to 73 years. Immunohistochemical
      analysis showed nuclear beta-catenin staining in 7 (39%) of the 18 cases. The
      cases with nuclear beta-catenin localization included 1 adenoma, 2 borderline
      IPMN, and 4 carcinomas in situ and/or invasive carcinomas. Seven cases showed
      absence of APC immunostaining and these included 4 cases with nuclear beta
      catenin localization. Fourteen cases displayed marked diffuse up-regulation of c
      myc protein, and 12 cases also showed diffuse cyclin D1 protein overexpression. E
      cadherin expression was intense and membrane in location (comparable to normal
      tissue) in 6 of 8 adenomas (no tissue was available in 1 case). Decreased E
      cadherin staining was noted in 8 cases where tissue was available for assessment.
      There was progressive decrease in membrane staining of E-cadherin in 2 of 3
      borderline lesions, 1 of 2 carcinomas in situ, and 4 of 5 invasive carcinomas.
      All other immunostains were either normal in distribution or did not show any
      correlation with beta-catenin or clinicopathologic parameters. In conclusion, 7
      (39%) of 18 cases of IPMN in this study demonstrated abnormal localization of
      beta-catenin, 4 of which also lacked APC expression. Of 5 carcinomas arising in
      IPMN, 4 displayed a decrease in E-cadherin expression. There was also a trend for
      the higher grades of IPMN to show nuclear localization of beta-catenin. These
      findings suggest that a proportion of cases of IPMN may show abnormalities in the
      Wnt-signaling pathway with consequent altered expression of downstream related
      proteins.

PMID- 16426923
TI  - Splenic small B-cell lymphoma with IGH/BCL3 translocation.
AB  - Isolated chromosomal translocations are important defining features of many non
      Hodgkin lymphomas, especially of B-cell type. In contrast to some other
      translocations, the significance of IGH/BCL3 translocations is not well defined.
      Although often considered a feature of the ill-defined entity atypical chronic
      lymphocytic leukemia, very few cases are reported in which involvement of BCL3
      and the precise B-cell neoplasm are both well documented. For this reason, we
      report a splenic-based CD5(-), CD10(-), CD43(-), CD23(-), CD103(-), FMC7(+),
      CD25(+) small B-cell lymphoma associated with epithelioid histiocyte clusters and
      a t(14;19)(q32;q13) representing an IGH/BCL3 translocation based on classical
      cytogenetic studies, chromosomal painting, and fluorescence in situ hybridization
      studies. The previously reported neoplasms with t(14;19)(q32;q13) or IGH/BCL3
      translocations are also reviewed. The present case did not fall into any of the
      classic B-cell lymphoma categories and clearly did not represent chronic
      lymphocytic leukemia/small lymphocytic lymphoma. This case suggests that the
      IGH/BCL3 translocation may help to define a new clinicopathologic entity.

PMID- 16426924
TI  - Multiple organ involvement in eosinophilic polymyositis: an autopsy report.
AB  - This report describes autopsy findings of eosinophilic polymyositis in a 29-year
      old woman. She complained of muscle pain and tenderness. A serum examination
      disclosed elevated creatine kinase, and echocardiography showed lowered cardiac
      function. Electromyography demonstrated myopathic potentials, and the skeletal
      muscle biopsy revealed degeneration of muscle fibers accompanying marked
      eosinophilic infiltration. Peripheral eosinophilia was not prominent. A systemic
      examination excluded possible etiologic factors, such as hypereosinophilic
      syndrome, collagen vascular diseases, or parasites. The patient died of heart
      failure after a 4-month clinical course. The autopsy disclosed a set of
      histological changes indicating tissue injuries, that is, loss of muscle fibers,
      interstitial fibrosis, and/or infiltrates of lymphocytes not only in the skeletal
      muscles and heart but also in various visceral organs. Eosinophils were sparsely
      scattered. These results indicate that the overrun of eosinophils underlying
      eosinophilic polymyositis, regardless of the presence of hypereosinophilic
      syndrome or other systemic disorders, could involve wide-ranging visceral organs.

PMID- 16426925
TI  - Acute myocardial infarction caused by coronary tumor thromboembolism: a rare
      primary manifestation of malignant tumor disease.
AB  - Myocardial infarction in the context of malignant tumor disease is rare but well
      documented and can occur through various pathophysiological mechanisms. We report
      an unusual case of a patient with recurrent myocardial infarction due to coronary
      tumor thromboembolism as the first clinical manifestation of a previously unknown
      squamous cell carcinoma of the lung. The possible pitfalls leading to a wrong
      preliminary diagnosis in our case as well as the literature on myocardial
      infarction in patients with cancer were discussed.

PMID- 16426926
TI  - A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of
      IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis).
AB  - There is now increasing evidence that IgG4 is closely involved in idiopathic
      sclerosing lesions, such as sclerosing pancreatitis and sclerosing sialadenitis.
      In this report, we describe a case of IgG4-related retroperitoneal and
      mediastinal fibroses. A 52-year-old man presented with dull back pain and was
      found to have a continuously surrounding paraaortic mass. A biopsy specimen taken
      from the retroperitoneum showed a diffuse lymphoplasmacytic infiltration
      intermixed with fibrosis. Many IgG4-positive plasma cells were demonstrated on
      immunostaining. His serum IgG4 concentration was 392 mg/dL (reference range,
      <70). We treated this patient with a corticosteroid, which markedly diminished
      the paraaortic mass along with lowering of his serum IgG4 concentration. The
      possible involvement of IgG4 was suggested in the pathogeneses of retroperitoneal
      and mediastinal fibroses in this patient. IgG4 might be useful in the clinical
      management of retroperitoneal or mediastinal fibrosis to differentiate them from
      malignant tumors and predict steroid sensitivity.

PMID- 16426927
TI  - Cleft formation and consumption of the epidermis in cutaneous melanocytic
      lesions.

PMID- 16426929
TI  - CD4+/CD56+ hematologic malignancy with rearranged MLL gene.

PMID- 16426930
TI  - Marital status, quality of life, and clinical outcome in patients with heart
      failure.
AB  - AIM: This study investigated the impact of having a partner on quality of life
      (QoL), the number of hospital readmissions, and 9-month survival in patients with
      heart failure (HF). METHODS: The study population consisted of hospitalized
      patients with HF. QoL was measured by the Cantril Ladder of Life (0-10) during
      hospital admission. Clinical data, readmission rate, and number of deaths were
      registered by patient interview and chart review. RESULTS: Of the 179 patients,
      96 (54%) were married or were living with a partner. Differences in QoL between
      married patients and those living alone were most pronounced with regard to
      future expectations of QoL (6.5 vs 5.0, P=.00). However, in a multivariate model
      QoL was primarily associated with socioeconomic status, age, and gender. Married
      patients had 12% less events in the 9-month follow-up period compared with
      patients living alone (P=not significant). CONCLUSION: This study indicates that
      most patients with HF who are living alone are mostly elderly women with a low
      socioeconomic status, who are at risk for recurrent events and a worse QoL.

PMID- 16426931
TI  - Self-care practices in women with diastolic heart failure.
AB  - BACKGROUND: For many patients with heart failure (HF), performing self-care is
      complicated by the complex medication regimen, symptom monitoring, and required
      decision-making. Women with HF are typically older and more physically
      debilitated, have more comorbidities, and may be at higher risk for poor self
      care practices. Previous studies have largely excluded patients with diastolic
      heart failure (DHF), however, so little is known about their self-care practices.
      OBJECTIVES: The purposes of the study were to describe the (a) performance of
      self-care behaviors and (b) demographic and clinical characteristics that
      affected self-care practices in women with DHF. METHODS: Thirty-two women who
      were 50 years of age or older and diagnosed with DHF were recruited through
      cardiologist referral from an outpatient HF clinic in an academic health care
      setting. Data were collected using a semistructured interview guide. Descriptive
      statistics were used to analyze participant demographic and clinical
      characteristics. The responses were tabulated in order of frequency and then
      coded into categories. RESULTS: The mean age of the women was 68 +/- 11 years;
      81% had annual incomes at or below the poverty level, 41% lived alone, and the
      majority had three or more comorbidities. Although most perceived their HF
      knowledge to be fair to good, and 62% had received HF educational information,
      only six (19%) weighed daily, few followed the recommended sodium restrictions,
      and 91% were sedentary at the time of the interview. The only self-care behavior
      that was consistently practiced (72%) was taking prescribed medications.
      Exertional intolerance often interfered with household chores and was cited most
      often as the reason for poorer quality of life. Decision-making about self-care
      activities such as taking diuretics was typically based on daily plans and social
      outings. Medical attention was sought only when acute or life-threatening
      symptoms occurred. Few women actively participated in ongoing symptom monitoring,
      and confusion over symptom recognition was a recurrent problem. CONCLUSIONS:
      Lower socioeconomic status and advancing age increase vulnerability for poor self
      care and negative clinical outcomes in women with DHF. Recommendations to improve
      self-care practices among economically disadvantaged women with HF such as
      prescribing routine activities as exercise, screening for depression, and home
      visits to increase socialization are discussed along with areas for future
      research.

PMID- 16426932
TI  - Clinical course of acute myocardial infarction in the hypertensive patient in
      Eastern Spain: the PRIMVAC registry.
AB  - OBJECTIVE: The study's objective was to analyze the acute complications and
      prognosis of acute myocardial infarction (AMI) in hypertensive patients in Spain.
      METHOD: Complications and early mortality were recorded among the patients with
      AMI admitted to the coronary care units of the 17 hospitals in the Valencia
      Community (Spain) between 1995 and 2000. RESULTS: A total of 12.071 patients were
      registered, of whom 46% were hypertensive (5.550 cases). Atrial fibrillation was
      more frequent in the hypertensive group, whereas ventricular fibrillation was
      more common among normotensive patients. We found higher mortality rates in the
      hypertensive group (14.4% vs 12.4%; P<.001). However, after multivariate
      adjustment, hypertension was not independently associated with mortality (odds
      ratio: .95; P=.46), and remained independently associated with a lower risk of
      primary ventricular fibrillation (odds ratio: .83; P<.05). CONCLUSION:
      Hypertensive patients do not present comparatively greater mortality during AMI,
      although primary ventricular fibrillation is less common in such subjects.

PMID- 16426933
TI  - Evaluating the reliability of recorded fluid balance to approximate body weight
      change in patients undergoing cardiac surgery.
AB  - OBJECTIVES: The objective of this study was to investigate body weight change in
      adult patients undergoing cardiac surgery and to assess the accuracy of
      conventional recorded fluid balance charting methods to reflect this change in
      body weight. DESIGN: This was a descriptive study. SETTING: This study was
      conducted at the cardiac care unit and medical-surgical intensive care unit (ICU)
      of a private hospital in Melbourne, Australia. SUBJECTS: The subjects were 32
      adult patients who underwent cardiac surgical procedures. Twenty-six were male,
      and the mean age was 67 years (range 36-84 years). Twenty-three patients
      underwent coronary artery bypass graft surgery, and nine patients underwent heart
      valve repair or replacement+/-coronary artery bypass graft surgery between
      December 2003 and May 2004. OUTCOME MEASURES: The measures were recorded fluid
      balance for the perioperative period together with body weight measurements from
      the night before surgery and immediately on discharge from the ICU. An additional
      body weight measurement on the seventh postoperative day provided a trajectory of
      body weight gain or loss for the period of hospitalization after surgery. A
      retrospective medical history audit and an HV-CS digital chair scale (A&D Mercury
      Pty Ltd, Victoria, Australia) were used to collect the data. RESULTS: Analysis
      revealed that 30 patients increased their body weight from the night before
      surgery until discharge from the ICU. The mean weight gain was 3.34 kg (standard
      deviation [SD] 1.17, 95% confidence interval 2.70-3.98, P<.001). The average
      preoperative body weight was 80.97 kg (SD 16.79), whereas the average ICU
      postoperative weight was 83.94 kg (SD 16.15). Twenty-six patients (81.25%) had
      returned to, or were below, their preoperative weight by their seventh
      postoperative day (M 2.96 kg, SD 2.24 kg, P<.05). The average recorded fluid
      balance during the perioperative period was +1.56 L (SD 2.59 L, P<.001) with a
      difference of 1.39 kg between the recorded fluid balance and measured body weight
      change. Three patients (9.75%) met the criteria for accurate recorded fluid
      balance, and eight patients (25%) experienced a net difference in the opposite
      direction between recorded fluid balance and body weight change during the
      perioperative period. CONCLUSION: Body weight in patients who undergo cardiac
      surgery was found to fluctuate over the perioperative period. Use of recorded
      fluid balance to reflect change in body weight for patients undergoing cardiac
      surgery was deemed unreliable. Further investigation of body weight change and
      scrutiny of conventional recorded fluid balance charting methods for patients who
      undergo cardiac surgery is needed.

PMID- 16426934
TI  - Uncertainty, symptom distress, anxiety, and functional status in patients
      awaiting coronary artery bypass surgery.
AB  - OBJECTIVE: The study's objective was to (1) describe uncertainty, anxiety, the
      symptom distress experience, and functional status of patients on a coronary
      artery bypass graft (CABG) waiting list and express the relationship between
      these concepts; (2) explore whether length of time waited has an influence on the
      psychosomatic condition of patients; and (3) explore the use of semistructured
      interviews within the context of a theoretic framework and compare open-ended
      responses to quantitative results. DESIGN: A descriptive, correlational, cross
      sectional design was used with supplementary telephone interviews using
      semistructured questions. Quantitative data were collected with a mailed
      questionnaire. Study instruments included the Mishel Uncertainty in Illness Scale
      (Community), Symptom Frequency and Symptom Distress Scale, Graphical Anxiety
      Rating Scale, and Kansas City Cardiomyopathy Questionnaire (Physical and Social
      Limitation). The Mishel Uncertainty in Illness Theory was used as the guiding
      theoretic framework. SETTING: The study took place in one large tertiary care
      hospital in Winnipeg, Manitoba, Canada. SAMPLE: The study included a convenience
      sample of 42 patients undergoing first-time elective CABG only, 25 of whom
      participated in the telephone interview. RESULTS: Average uncertainty and anxiety
      were present at moderate levels and were associated with moderate deterioration
      of functional status. Reported symptom distress was low; however, presence of
      symptoms showed a strong relationship with anxiety (P=.0002), and this
      relationship was confirmed through semistructured interviews. Although the
      relationship between uncertainty and anxiety was nonsignificant, the interviews
      suggest positive views of uncertainty as an opportunity may have muted the
      relationship between uncertainty and anxiety, and that it is possible to
      experience uncertainty as a danger and an opportunity simultaneously. No
      statistically significant relationship was found between the study variables and
      waiting time; however, there was a nonsignificant trend toward deterioration of
      psychologic and physical condition with longer waits, which may be clinically
      significant. CONCLUSION: Psychosocial distress and physical condition among
      patients on CABG waiting lists should be continually assessed in all patients
      regardless of how long they have been waiting. Each patient will have a unique
      presentation of symptoms and a corresponding unique psychologic response.

PMID- 16426936
TI  - Does coexistence with bronchiectasis influence intensive care unit outcome in
      patients with chronic obstructive pulmonary disease?
AB  - BACKGROUND: Bronchiectasis is associated with chronic obstructive pulmonary
      disease (COPD) in 30% to 50% of patients. This study evaluated whether
      association with bronchiectasis has any influence on morbidity and mortality in
      patients with COPD during their intensive care unit (ICU) stay. METHODS: The
      study was conducted at a respiratory ICU of a university hospital, and 93
      mechanically ventilated patients with COPD were studied. Twenty-nine (31%) of 93
      patients with COPD also had bronchiectasis. Patients with bronchiectasis had more
      frequent hospitalizations, more severe airflow limitation, and higher pulmonary
      artery pressure than patients without bronchiectasis. Duration of ICU (27+/-32
      days [median: 14]; 16+/-16 days [median: 9]; P=.01) and hospital stays (44+/-44
      days [median: 24.5]; 28+/-26 days (median: 20); P=.046) in patients with
      bronchiectasis were significantly longer than in patients without bronchiectasis,
      respectively. Bronchiectasis was an independent predictor for ICU stay longer
      than 10 days (odds ratio: 5, 95% confidence interval: 1.02-21, P=.043). The
      development rate of ventilator-associated pneumonia, especially with Pseudomonas
      aeruginosa, was significantly higher in patients with bronchiectasis (P=.034).
      Despite these prolonged durations, bronchiectasis did not increase mortality in
      this study population (P=.865). RESULTS: These results suggest that the
      coexistence of bronchiectasis in patients with COPD may increase the duration of
      ICU stay and hospitalization but does not influence the mortality.

PMID- 16426935
TI  - Coping and psychological distress in hospitalized patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Previous studies have emphasized the importance of coping in patients
      with chronic obstructive pulmonary disease (COPD). In other medical conditions,
      inadequate coping is associated with higher levels of psychological distress.
      Therefore, the types of coping strategies that patients use may also influence
      the distress that accompanies an acute exacerbation of COPD. OBJECTIVES: The
      objective was to examine the prevalence of psychological distress in patients
      hospitalized for an acute exacerbation COPD, assess how they appraise and cope
      with the recent stressful event, and examine the relationships among coping,
      appraisal, and psychological distress. THEORETIC FRAMEWORK: Lazarus and Folkman's
      cognitive-motivational-relational meta-theory guided this study. METHODS: A
      descriptive, cross-sectional design was used to analyze baseline data from 92
      participants of a longitudinal study of patients hospitalized with an acute
      exacerbation of COPD and followed for up to 9 months after discharge. The
      baseline interview included an assessment of demographic and clinical
      characteristics, coping, appraisal, and psychological distress. RESULTS: The
      majority of patients demonstrated psychological distress (64%), identified their
      current breathing problem as their stressful event (68.5%), and appraised the
      mean intensity of the event at 5.57+/-1.55 (scale range: 1, not stressful to 7,
      most stressful). Approximately half of the respondents (51%) characterized the
      stressful event as representing a threat, 26% as harmful, 7.6% as a loss, 4.3% as
      a challenge, and 11% chose other terms to characterize the stressful event. The
      majority of patients (61%) reported that the stressful event was something they
      had to accept, 21.7% thought they could change or do something about it, and the
      remainder needed more information. There were no significant differences between
      patients with and without psychological distress with regard to demographic
      characteristics, disease severity (forced expiratory volume in 1 second), types
      of stressful event, stress intensity, primary or secondary appraisal, or number
      of coping strategies used. However, problem-solving coping strategies were
      inversely related to psychological distress. CONCLUSIONS: Timely identification
      and use of problem-solving coping strategies may help reduce the psychological
      distress experienced during acute hospitalizations for COPD.

PMID- 16426937
TI  - Pleural effusion causing cardiac tamponade: report of two cases and review of the
      literature.
AB  - We report on two patients who developed large left-sided pleural effusions in
      association with hemodynamic compromise. In both cases transthoracic
      echocardiography demonstrated left ventricular diastolic collapse confirming our
      clinical suspicion of cardiac tamponade. Large-volume thoracentesis in the first
      case and thoracotomy with drainage of the pleural collection in the second case
      resulted in immediate hemodynamic improvement. Our report shows that large
      pleural effusions can result in impaired cardiac filling and a tamponade-like
      physiology. Thoracentesis in this setting can lead to rapid improvement of the
      hemodynamic profile.

PMID- 16426938
TI  - A new face of Wenckebach.

PMID- 16426939
TI  - Fever of unknown origin caused by late-onset rheumatoid arthritis.
AB  - Fever of unknown origin (FUO) is always a diagnostic challenge. The causes of FUO
      are legion and may be due to malignancy, infection, collagen vascular disease,
      and a variety of other unusual disorders. Currently, malignancies-followed by
      infectious etiologies-are the most common cause of FUO. We present an elderly
      female patient with an FUO who was thought to have subacute bacterial
      endocarditis because of an antecedent history of recent dental work. Subacute
      bacterial endocarditis was ruled out on the basis of negative cultures and
      negative transesophageal echocardiography. No evidence for an infectious disease
      or neoplastic etiology could be demonstrated in this patient. The diagnosis of
      FUO is most difficult when there is a paucity of clues from the history and
      physical examination, as was the case in this patient. Nonspecific laboratory
      tests included highly increased erythrocyte sedimentation rate (>or=100 mm/h),
      highly increased C-reactive protein, relative lymphocytopenia, and chronic
      thrombocytosis. These findings are compatible with a variety of infectious and
      inflammatory disorders. No evidence could be found for vasculitis. The only
      laboratory diagnostic findings present in her case were a highly increased
      rheumatoid factor titer and perinuclear antineutrophilic cytoplasmic antibody
      level. Polymyalgia rheumatica/temporal arteritis, systemic lupus erythematosus,
      and adult Still's disease were ruled out. The patient's FUO was best explained by
      the finding of late-onset rheumatoid arthritis (LORA), which is characterized by
      acute onset in elderly patients without the usual musculoskeletal manifestations
      of rheumatoid arthritis. Both the highly increased rheumatoid factor titer and
      perinuclear antineutrophilic cytoplasmic antibody level in the absence of an
      alternate explanation indicate that the FUO in this patient was caused by LORA.

PMID- 16426941
TI  - Chronic graft-versus-host disease.
AB  - Chronic graft versus host disease (GVHD) remains today one of the most vexing
      late complications of allogeneic stem cell transplantation. Occurring a minimum
      of 100 days following stem cell transplantation, approximately 50% of patients
      will experience some degree of chronic GVHD. Host-reactive lymphocytes of donor
      origin are the cells responsible for the "alloimmune" attack. The increased use
      of hematopoietic stem cells collected from the peripheral blood instead of bone
      marrow and the increasing age of stem cell transplant recipients has led to a
      higher incidence of chronic GVHD. Chronic GVHD most commonly affects the skin,
      liver, eyes or the mouth, however multiple other sites may also be affected.
      Chronic GVHD and the medications used to treat it result in a profoundly
      immunocompromised state. Death due to severe chronic GVHD is usually a
      consequence of infectious complications. Standard treatment for severe chronic
      GVHD is a combination of cyclosporine and prednisone. An alternating day regimen
      of these two agents prolongs survival and reduces drug-related adverse events.
      Topical therapy to affected areas is preferred for patients with mild disease.
      The 10-year survival of patients with mild chronic GVHD is approximately 80%, but
      is less than 5% for patients affected by severe chronic GVHD.

PMID- 16426940
TI  - The fundamental role of epigenetics in hematopoietic malignancies.
AB  - The term epigenetics defines a heritable alteration in gene expression without an
      accompanying change in primary DNA sequence. Two major mechanisms that foster
      epigenetic changes are DNA methylation at cytosine bases within a CpG
      dinucleotide and post-translational histone modifications. Disruption of the
      balanced epigenetic network may have significant impact on chromatin structure
      and transcriptional activity. DNA methylation patterns are profoundly deranged in
      human cancer and comprise genome-wide losses as well as regional gains in DNA
      methylation. Hypermethylation of CpG islands within gene promoter regions in
      collaboration with deacetylation and other modifications of key histone amino
      acids is associated with transcriptional inactivation and represents, in addition
      to genetic aberrations, an important mechanism of gene silencing in the
      pathogenesis of human cancer. These epigenetic events act as alternatives to
      mutations and deletions to disrupt tumor suppressor gene function. A large number
      of genes involving fundamental cellular pathways may be affected by aberrant CpG
      island methylation in association with transcriptional silencing in virtually all
      tumor types. Altered DNA methylation patterns may serve as biomarkers for cancer
      detection, assessment of prognosis, and prediction of response to therapy.
      Furthermore, clinical trials using epigenetically targeted therapies have yielded
      promising results in hematopoietic malignancies. The ongoing exploration of basic
      events involved in altered gene transcription patterns and continued clinical
      investigative studies are helping to develop novel strategies for the diagnosis,
      prevention, and treatment of human cancer.

PMID- 16426942
TI  - Molecular monitoring of BCR-ABL as a guide to clinical management in chronic
      myeloid leukaemia.
AB  - Molecular monitoring of BCR-ABL transcript levels by real-time quantitative PCR
      is increasingly used to assess treatment response in patients with chronic
      myeloid leukaemia (CML). This has become particularly relevant in the era of
      imatinib therapy when residual levels of leukaemia usually fall below the level
      of detection by bone marrow cytogenetic analysis. Studies of imatinib-treated
      patients have determined that BCR-ABL levels measured early in therapy can
      predict subsequent response and the probability of acquired resistance. The
      defining of a molecular level of response that indicates a high probability of
      progression-free survival highlights the relevance of molecular analysis for
      clinical management. Small increases in the BCR-ABL level can identify patients
      with kinase domain mutations that lead to imatinib resistance. Therefore, these
      assays can be used as a screening strategy for mutation analysis. As second
      generation kinase inhibitors commence clinical trials, the molecular response
      will be a primary end-point that determines efficacy.

PMID- 16426943
TI  - Thrombotic thrombocytopenic purpura: aetiology, pathophysiology and treatment.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare disorder whose varied
      clinical manifestations result from the formation of platelet-rich thrombi within
      the microvasculature and consequent tissue ischaemia. This review will outline
      how, in the eighty years since its initial description, scientific discoveries
      have not only led to a deeper understanding of the fundamental pathophysiology of
      TTP, but have also contributed to advances in the clinical management of this
      condition. Current research in this field will hopefully provide the basis for
      the design and development of novel therapeutic strategies.

PMID- 16426945
TI  - Published reports of acupuncture trials showed important limitations.
AB  - BACKGROUND: Systematic reviewers generally evaluate randomized controlled trials
      (RCTs) based on the published reports. We evaluated whether the description of
      methods in the published reports is an accurate and complete reflection of study
      procedures used. METHODS: The authors of 51 RCTs included in a systematic review
      of acupuncture for chronic pain were sent a brief survey that included questions
      related to the following three important study quality dimensions: (1) generation
      of allocation sequence, (2) allocation concealment, and (3) blinding of outcomes
      assessor. RESULTS: We received 35 of 51 responses for an overall response rate of
      68.6%. Of 35 studies described as randomized in published reports, associated
      survey responses indicated that four actually used quasi-randomized methods.
      Among published reports with missing information on these quality dimensions, 27
      of 32 studies used adequate methods for the generation of allocation sequence, 13
      of 34 used adequate allocation concealment and 2 of 10 were blinded, according to
      survey responses. Survey responses generally confirmed information about
      randomization and blinding already described in investigators' RCT publications.
      CONCLUSION: Surveying RCT investigators uncovered some information about study
      quality dimensions not described in published reports.

PMID- 16426946
TI  - Measures of familial aggregation depend on definition of family history: meta
      analysis for colorectal cancer.
AB  - OBJECTIVE: Familial aggregation, a primary theme in genetic epidemiology, can be
      estimated from family studies based on an index person. The excess risk due to
      the presence of affected family members can be classified according to whether
      disease in the relatives is considered a risk factor for the index person (type I
      relative risk) or whether the disease status of the index person is considered a
      risk factor for the relatives (type II relative risk). STUDY DESIGN AND SETTING:
      A meta-analysis of published colorectal cancer studies reporting a measure of
      familial association was performed and application of multilevel linear
      regression to model age-specific relative risks presented. RESULTS: The pooled
      type I relative risk of colorectal cancer given any affected first-degree
      relative (based on 20 studies) was 2.26 (95% confidence interval CI = 1.86, 2.73)
      and decreased with the age of the consultand. The pooled type II estimate (based
      on seven studies) was 2.81 (95% CI = 2.05, 3.85). CONCLUSION: Type I relative
      risks are useful in clinical counseling settings when a consultand wants to know
      his/her disease risk given his or her family history. Type II relative risks can
      be used to quantify the risk of disease to relatives of an affected individual
      and then identify subjects eligible for screening.

PMID- 16426947
TI  - Methodology of studies evaluating death certificate accuracy were flawed.
AB  - BACKGROUND AND OBJECTIVE: Statistics on causes of death are important for
      epidemiologic research. Studies that evaluate the source data often give
      conflicting results, which raise questions about comparability and validity of
      methods. METHODS: For 44 recent evaluation studies we examined the methods
      employed and assessed the reproducibility. RESULTS: Thirty studies stated who
      reviewed the source data. Six studies reported reliability tests. Twelve studies
      included all causes of death, but none specified criteria for identifying the
      underlying cause when several, etiologically independent conditions were present.
      We assessed these as not reproducible. Of 32 studies that focussed on a specific
      condition, 21 provided diagnostic criteria such that the verification of the
      focal diagnosis is reproducible. Of 16 that discussed the difference between
      dying "with" and "from" a condition, eight described how competing causes had
      been handled. For these eight, the selection of a principal cause is
      reproducible, but in three the selection strategy conflicts with the
      international instructions issued by the World Health Organization. CONCLUSION:
      Methods and criteria are often insufficiently described. When described, they
      sometimes disagree with the international standard. Explicit descriptions of
      methods and criteria would contribute to methodologic improvement and would allow
      readers to assess the generalizability of the conclusions.

PMID- 16426948
TI  - Some prognostic models for traumatic brain injury were not valid.
AB  - OBJECTIVE: Various prognostic models have been developed to predict outcome after
      traumatic brain injury (TBI). We aimed to determine the validity of six models
      that used baseline clinical and computed tomographic characteristics to predict
      mortality or unfavorable outcome at 6 months or later after severe or moderate
      TBI. STUDY DESIGN AND SETTING: The validity was studied in two selected series of
      TBI patients enrolled in clinical trials (Tirilazad trials; n = 2,269;
      International Selfotel Trial; n = 409) and in two unselected series of patients
      consecutively admitted to participating centers (European Brain Injury Consortium
      [EBIC] survey; n = 796; Traumatic Coma Data Bank; n = 746). Validity was
      indicated by discriminative ability (AUC) and calibration (Hosmer-Lemeshow
      goodness-of-fit test). RESULTS: The models varied in number of predictors (four
      to seven) and in development technique (two prediction trees and four logistic
      regression models). Discriminative ability varied widely (AUC: .61-.89), but
      calibration was poor for most models. Better discrimination was observed for
      logistic regression models compared with trees, and for models including more
      predictors. Further, discrimination was better when tested on unselected series
      that contained more heterogeneous populations. CONCLUSION: Our findings emphasize
      the need for external validation of prognostic models. The satisfactory
      discrimination indicates that logistic regression models, developed on large
      samples, can be used for classifying TBI patients according to prognostic risk.

PMID- 16426949
TI  - Estimated progression rates in three United Kingdom hepatitis C cohorts differed
      according to method of recruitment.
AB  - OBJECTIVES: To estimate hepatitis C virus (HCV) progression rates between disease
      stages prior to cirrhosis, using data from liver biopsies in three observational
      cohorts. To demonstrate how the method of cohort recruitment can influence the
      estimation of HCV-progression rates. STUDY DESIGN AND SETTING: Data came from
      three United Kingdom observational cohorts, assembled from different referral
      sources. In total, 987 HCV-infected patients with an estimated (or known) date of
      infection and at least one histologically scored liver biopsy were eligible for
      inclusion in the analysis. Liver biopsy scores were used to determine the stage
      of HCV-related liver disease. A three-state continuous time Markov model was used
      to estimate covariate-specific average probabilities of progression of disease.
      RESULTS: After adjusting for confounders, considerably different rates of disease
      progression were estimated in the three cohorts. For a group of patients with the
      same demographics, the estimated 20-year probability of progression to cirrhosis
      was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95%
      CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort
      recruited from a tertiary referral center. CONCLUSION: Researchers using
      estimates of disease progression should be aware that the method of cohort
      recruitment has considerable influence on the progression rates that are derived.

PMID- 16426950
TI  - Proxy respondents reliably assessed the quality of life of elective cardiac
      surgery patients.
AB  - BACKGROUND AND OBJECTIVE: The level of agreement between index and proxy
      respondents on assessment of health status of clinical cohorts is variable. There
      is limited information regarding agreement between cardiac surgery patients and
      their proxies, and levels of agreement examined across repeated measures. This
      study examined the level of agreement between index and proxy respondents'
      perceptions of the patient's health status prior to and following cardiac
      surgery. METHODS: A prospective, paired-respondent, repeated measures
      observational study of elective cardiac surgical patients and their next of kin,
      from the cardiac surgical unit of a tertiary hospital in Sydney, Australia.
      Health status domains were examined using the15D and SF-36 instruments at three
      points: prior to surgery, at hospital discharge, and at 6 months post discharge.
      RESULTS: Moderate to good level of agreement was noted for physical function
      (physical functioning, role functioning-physical, mobility, breathing, speech,
      hearing, usual activities, sexual activities) and some psychosocial dimensions
      (role functioning-emotional, sleeping, depression, mental health). Agreement was
      highest for presurgery and 6 months post discharge. Differences in scores were
      not clinically important. CONCLUSION: Proxy respondents can reliably assess the
      quality of life of a cardiac surgical patient using 15D or SF-36, particularly
      for domains reflecting physical function.

PMID- 16426951
TI  - Performance measures were necessary to obtain a complete picture of
      osteoarthritic patients.
AB  - OBJECTIVES: Self-report questionnaires and performance measures represent two
      methods for assessing physical function. A recurring theme is that self-report
      measures are superior to performance measures. This study investigated the
      association between three performance test outcomes of four activities (pain,
      exertion, and time or distance; for self-paced walk, stair test, timed up-and-go,
      6-minute walk) with self-reports of physical function (WOMAC Physical Function
      subscale and LEFS) and the association between the change scores of the
      performance tests and those of the self-report measures. STUDY DESIGN AND
      SETTING: Performance and self-report measures were administered three times
      (presurgery and at approximately 1 week and approximately 8 weeks post
      arthroplasty) to 85 patients who underwent total hip or knee arthroplasty.
      Components of the performance tests were pooled within each domain across the
      four measures. Multiple regression analyses were applied. Independent variables
      were performance tests components; dependent variables were self-report measures.
      Standardized regression coefficients described the cross-sectional and
      longitudinal associations. RESULTS: Pain was the principal determinant of WOMAC
      Physical Function subscale scores. Pain, exertion, and time or distance were
      strongly associated with the LEFS at the first, second, and third assessments,
      respectively. Change in pain was most strongly associated with change in self
      reported physical function. CONCLUSION: Our findings caution against the isolated
      use of self-report assessments of physical function.

PMID- 16426952
TI  - A new instrument for targeting falls prevention interventions was accurate and
      clinically applicable in a hospital setting.
AB  - BACKGROUND AND OBJECTIVE: To describe the diagnostic accuracy and practical
      application of the Peter James Centre Falls Risk Assessment Tool (PJC-FRAT), a
      multidisciplinary falls risk screening and intervention deployment instrument.
      METHODS: In phase 1, the accuracy of the PJC-FRAT was prospectively compared to a
      gold standard (the STRATIFY) on a cohort of subacute hospital patients (n = 122).
      In phase 2, the PJC-FRAT was temporally reassessed using a subsequent cohort (n =
      316), with results compared to those of phase 1. Primary outcomes were falls
      (events), fallers (patients who fell), and hospital completion rates of the PJC
      FRAT. RESULTS: In phase 1, PJC-FRAT accuracy of identifying fallers showed
      sensitivity of 73% (bootstrap 95% confidence interval CI = 55, 90) and
      specificity of 75% (95% CI = 66, 83), compared with the STRATIFY (cutoff > or =
      2/5) sensitivity of 77% (95% CI = 59, 92) and specificity of 51% (95% CI = 41,
      61). This difference was not significant. In phase 2, accuracy of nursing staff
      using the PJC-FRAT was lower. PJC-FRAT completion rates varied among disciplines
      over both phases: nurses and physiotherapists, > or =90%; occupational
      therapists, > or =82%; and medical officers, > or =57%. CONCLUSION: The PJC-FRAT
      was practical and relatively accurate as a predictor of falls and a deployment
      instrument for falls prevention interventions, although continued staff education
      may be necessary to maintain its accuracy.

PMID- 16426953
TI  - Distribution-based and anchor-based approaches provided different
      interpretability estimates for the Hydrocephalus Outcome Questionnaire.
AB  - OBJECTIVE: To compare three separate methods for establishing interpretability
      for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ). STUDY
      DESIGN AND SETTING: The mothers of children with hydrocephalus attending the
      outpatient clinics at a pediatric hospital completed the HOQ (for which scores
      can range from 0 to 1.0 with the smallest possible incremental change being
      .005), the Health Utilities Index-2 (HUI-2), and a global rating of their child's
      health. The surgeon for the child also provided a global rating of the child's
      health following their visit. These data were used to calculate (i) the minimal
      important difference (MID) based on global health ratings, (ii) the MID based on
      an effect size approach, and (iii) the conversion of numerical HOQ scores into
      health utility scores obtained from the HUI-2. RESULTS: Based on mothers'
      responses (n = 79) and surgeons' responses (n = 61), respectively, the MID for
      the HOQ was estimated to be .12 and .10. Using the effect size approach, the MID
      was estimated to be much lower at .03. HOQ scores were found to be readily
      translatable to HUI-2 utility scores using a simple linear transformation. The
      mean utility score for this sample of patients was .77. CONCLUSIONS: Two methods
      for determining the MID yielded quantitatively different results. Conversion of
      numerical health status scores to utility scores was done successfully and
      providing another element of interpretability.

PMID- 16426954
TI  - Quality of life scores differed according to mode of administration in a review
      of three major oncology questionnaires.
AB  - OBJECTIVE: To assess whether scores on the three major quality-of-life
      questionnaires in oncology (FACT-G, FLIC, and EORTC QLQ-C30) are associated with
      modes of administration in a realistic clinical research setting. STUDY DESIGN
      AND SETTING: A heterogeneous sample of 1,265 cancer patients was recruited in
      Singapore. About one-fourth of the patients chose to have the interview
      administered by research staff; the rest self-completed the questionnaires.
      Multiple regression was used to adjust for differences in demographic and
      clinical characteristics between patients. An equivalence margin was defined as
      0.25 standard deviations. RESULTS: Apart from one exception (the EORTC QLQ-C30
      global functioning scale), all scales showed higher mean values in patients who
      were interviewed than patients who self-administered the questionnaires. For the
      physical and functional well-being scales of FACT-G and the physical and social
      functioning scales of EORTC QLQ-C30, the differences were small and the
      confidence intervals fell totally within the equivalence zone. The emotional well
      being score of the FACT-G was different across modes of administration and the
      confidence interval fell outside the equivalence zones. There was no interaction
      between modes of administration and respondents' education level. CONCLUSION: The
      physical aspect of quality-of-life is not sensitive to interviewer administration
      but the psychological aspect is. Statistical adjustment for some scales is
      recommended.

PMID- 16426955
TI  - The new questionnaire health-related quality of life for eating disorders showed
      good validity and reliability.
AB  - BACKGROUND AND OBJECTIVES: To describe the development and investigate the
      psychometric properties of a new instrument to measure health-related quality of
      life (HRQoL) for individuals with an eating disorder (ED). METHODS: Seven focus
      groups were convened and an extensive literature review was carried out to
      generate the items. The first draft of the questionnaire was pilot tested. Three
      hundred twenty-four ED patients took part in the final field study. The 12-Item
      Short Form Health Survey, the Eating Attitudes Test-26, and two items from the
      Eating Disorders Inventory-2 also were applied to examine the concurrent
      validity. Factor analysis, item scale correlation correcting for overlap, test
      retest, Cronbach's alpha coefficient, known-groups validation, and the
      sensitivity of the questionnaire in different populations also were examined.
      RESULTS: The final Health-Related Quality of Life in Eating Disorders (HeRQoLED)
      questionnaire consisted of 50 items. Principal axis factor analysis identified
      eight subscales. Concurrent validity showed correlations >.40 with the criteria
      measures. Excellent reliability and stability were obtained. The HeRQoLED was
      sensitive in discriminating both between known-different groups and from the
      general population. CONCLUSION: The results provide evidence of the good
      psychometric properties of the new HeRQoLED questionnaire, except for one domain,
      which had to be eliminated.

PMID- 16426956
TI  - In a randomized controlled trial, cataract surgery in both eyes increased
      benefits compared to surgery in one eye only.
AB  - BACKGROUND AND OBJECTIVE: Despite recommendation of surgery in both eyes in
      patients with bilateral cataract, there is little evidence about the benefits of
      second-eye surgery. The objective of this study was to compare the benefits of
      cataract surgery in both eyes with those of surgery in one eye only. STUDY DESIGN
      AND SETTING: Two-arm randomized controlled trial involving 296 patients with
      bilateral cataracts of two public teaching hospitals. Patients were randomly
      assigned to receive surgery in one eye only (control group) or surgery in both
      eyes, one eye at a time (intervention group). The main outcome measures were
      binocular visual acuity, binocular contrast sensitivity, stereopsis, and patient
      reported visual disability (VF-14), measured 4-6 months postoperatively. RESULTS:
      A total of 135 (91.2%) and 139 (93.9%) patients completed the trial in the
      control and intervention groups, respectively. Postoperatively, intervention
      group presented a better visual acuity (difference of 0.07; 95% CI = 0.03, 0.12),
      stereopsis (0.62 log sec arc; 95% CI = 0.45, 0.79), and VF-14 (8.2 points; 95% CI
      = 4.4, 12.4). No significant differences were found for contrast sensitivity.
      CONCLUSIONS: Bilateral cataract patients should have surgery in both eyes.
      Including stereopsis and patient-reported visual disability in the assessment of
      cataract patients, especially after first-eye surgery, will improve the
      evaluation of effectiveness.

PMID- 16426958
TI  - Effect of micronutrient supplement on health and nutritional status of
      schoolchildren: study design.
AB  - OBJECTIVE: We tested the hypothesis that supplementation with a micronutrient
      fortified beverage improves micronutrient status and physical and mental
      development in apparently healthy schoolchildren. METHODS: The study was carried
      out in middle-income students in two residential schools that catered to children
      from a semi-urban population near Hyderabad, India. Included were 869 children
      who were 6 to 16 y of age in grades 1 to 10. Because children at each grade were
      distributed across two classrooms (clusters) and were homogeneous, each grade was
      considered to consist of a matched pair. There were thus 10 pairs available for
      the study. Classes in each grade were randomized to receive a micronutrient
      enriched beverage or a placebo without added micronutrients. The study was double
      blinded and the duration was 14 mo, with supervised feeding of the micronutrient
      enriched beverage. The effect of the micronutrients on the outcome variables
      growth, biochemical status, mental function, and bone health were assessed.
      RESULTS: The number of matched pairs varied between seven and eight, and the
      required number of children per treatment group ranged from 32 in the case of
      bone heath to 177 for body weight. The power of the outcome variables ranged from
      74% to 100% and was adequate for successful pairing. The effect assessed at the
      end of supplementation showed that the intervention was beneficial. CONCLUSIONS:
      Designing an intervention, choosing outcome variables, and implementing the
      protocol in a typical Indian school setting were achieved.

PMID- 16426957
TI  - Different factor loadings for SF36: the Strong Heart Study and the National
      Survey of Functional Health Status.
AB  - BACKGROUND: To increase our understanding of the psychometric characteristics and
      factor structure of the SF36 in older American Indian populations. METHODS:
      Between 1993 and 1995, SF36 data were collected from 3,488 Phase II participants
      of the Strong Heart Study (SHS) between the ages of 48 and 81. Comparison data
      were provided by an age- and gender-matched sample (n = 695) from the National
      Survey of Functional Health Status (NSFHS) conducted in 1989 and 1990. RESULTS:
      Generally, the basic psychometric analyses showed that the SF36 performed
      adequately in these older American Indians. Exploratory factor analyses indicated
      that a one-factor model best fit the data for both older groups. On the other
      hand, confirmatory factor analyses showed that a two-factor model with correlated
      factors provided a superior fit to the data than a one-factor model. An
      assumption of equivalent factor loadings for the SHS and NSFHS groups was
      untenable. CONCLUSION: These analyses demonstrate that use of summary scores
      assuming a differentiated physical/mental functioning structure is likely
      improper in at least some populations. The SF36 provides an important opportunity
      to understand cultural differences in the conceptualization and measurement of
      health-related quality of life.

PMID- 16426959
TI  - Effect of micronutrient supplement on health and nutritional status of
      schoolchildren: biochemical status.
AB  - OBJECTIVE: We assessed the effect of a daily intake of a micronutrient-fortified
      beverage for 14 mo on indicators of biochemical status of important
      micronutrients in schoolchildren. METHODS: A double-blind, placebo-controlled,
      matched-pair, cluster, randomization study design was used. Biochemical
      indicators of micronutrient status were evaluated at baseline and at the end of
      14 mo on a subsample in nine matched pairs. Prevalence (percentage) of
      subclinical deficiency, mean, and mean increments of each indicator were compared
      between supplemented and placebo groups. RESULTS: Extent of inadequacy at
      baseline was more or less 100% for folic acid, 65% for vitamins B2 and B6, and
      55% for vitamins C and A. Prevalence of anemia among subjects was 55%, with
      inadequacy of vitamin B12 being 40% and that of vitamin D being 30%. No subject
      had inadequacy of iodine based on urinary iodine. Supplementation of a
      micronutrient-enriched beverage for 14 mo significantly improved the status of
      many of the nutrients. The effect was significant with respect to vitamins A, B2,
      and B12, folic acid, vitamin D, parathyroid hormone, and thyroid-stimulating
      hormone in children who received the supplement compared with those who received
      only placebo. Hemoglobin status improved only in children who had anemia in the
      supplemented group. CONCLUSIONS: Prevalence of multiple subclinical micronutrient
      deficiencies are high in middle-income Indian school children. Daily consumption
      of a micronutrient-enriched beverage had positive effects that were confined to
      those nutrients that were inadequate at baseline.

PMID- 16426960
TI  - Effect of micronutrient supplement on health and nutritional status of
      schoolchildren: mental function.
AB  - OBJECTIVE: We evaluated the effect of a micronutrient-fortified beverage on
      mental function in schoolchildren. METHODS: This double-blind, placebo
      controlled, matched-pair, cluster, randomized feeding trial assessed baseline
      before supplementation and after 14 mo in a cohort of 608 children aged 6 to 15 y
      who received a micronutrient-fortified beverage or placebo. Children in two
      classes (clusters) in each of nine grades were assessed for intelligence,
      attention and concentration, memory, and school achievement. RESULTS: Mean
      intelligence quotient scores of the micronutrient-fortified beverage group and
      the placebo group at baseline and final follow-up were not significantly
      different. Mean verbal and performance scores and increments were also not
      different. After supplementation, attention-concentration increment scores of the
      micronutrient group were significantly higher (P < 0.05) than those of the
      placebo group. Mean and incremental scores of the supplemented group on the
      memory scale were not significantly different from those of the placebo group.
      CONCLUSIONS: Supplementation with a beverage fortified with a range of
      micronutrients significantly improved attention-concentration over 14 mo, but not
      intelligence quotient, memory, or school achievement among middle-income
      schoolchildren.

PMID- 16426961
TI  - Effect of micronutrient supplement on health and nutritional status of
      schoolchildren: bone health and body composition.
AB  - OBJECTIVE: We investigated the effect of a micronutrient-enriched beverage on
      body composition, bone mineral content (BMC), bone area, and bone mineral density
      (BMD) at various sites in schoolchildren. METHODS: A double-blind, placebo
      controlled, matched-pair, cluster, randomization study was carried out in
      residential schoolchildren 6 to 16 y of age who lived near Hyderabad, India.
      Children (n = 268) were selected randomly from two classes of each grade (1 to 9)
      and were provided a micronutrient-enriched beverage (n = 146) or a placebo drink
      (n = 122). Bone parameters such as BMC, BMD, and bone area at various sites and
      the entire body were measured with dual-energy X-ray absorptiometry at the
      beginning and end of the study. Increments of outcome variables were subjected to
      paired t test with appropriate corrections to assess the effect of the supplement
      on bone health. RESULTS: After 14 mo, increments for height, weight, fat-free
      mass, percentage of fat, whole-body BMC, whole-body bone area, and BMD at the
      neck of the femur were significantly greater (P < 0.05) in the supplemented group
      than in the placebo group. CONCLUSIONS: The micronutrient-rich supplement
      increased tissue growth and skeletal shell in apparently normal children in the
      14-mo period. It did not increase whole-body or site-specific BMD except at the
      neck of the femur. Amounts of calcium and other nutrients contained in the
      supplement were inadequate for tissue growth with density increases. This study
      raises important questions about the nutrient requirements of Indian children who
      consume a diet of cereals and pulses.

PMID- 16426962
TI  - Effect of micronutrient supplementation on health and nutritional status of
      schoolchildren: growth and morbidity.
AB  - OBJECTIVE: We evaluated the effect of a micronutrient-fortified beverage on
      growth and morbidity in apparently healthy schoolchildren. METHODS: This was a
      double-blind, placebo-controlled, matched-pair, cluster, randomized study in semi
      urban middle-income residential schoolchildren aged 6 to 16 y. Anthropometrics
      (height and weight), clinical symptoms of deficiency, and morbidity data were
      collected at baseline in the supplemented group (n = 446 in 10 grades) and the
      placebo group (n = 423 in 10 grades) and after 14 mo of supplementation (n = 355
      in the supplement group and n = 340 in the placebo group from nine pairs).
      RESULTS: After 14 mo of supplementation, there was a significant increase in mean
      increments of height and weight z scores of -0.04 and 0.02, respectively, in the
      supplemented group compared with -0.14 and -0.09 in the placebo group. Velocity
      of weight (3.56 versus 3.00) was significantly (P < 0.01) higher with
      supplementation. Although there were no differences in the incidence of common
      childhood diseases such as fever, cough and cold, diarrhea, and ear infections
      elicited for a reference period of 1 mo at every quarterly follow-up examination,
      the mean duration of illness (calculated per person per year) was significantly
      shorter (5.0 d) in the supplemented group than in the placebo group (7.4 d).
      CONCLUSIONS: The micronutrient-fortified beverage was beneficial in promoting
      growth and decreasing duration of common illnesses among middle-class residential
      schoolchildren who had adequate energy and protein intakes.

PMID- 16426963
TI  - Holding back the tide of antibiotic resistance.

PMID- 16426964
TI  - A global view of metabolites.
AB  - Fungi are rich sources of medically useful, as well as toxic, secondary
      metabolites. In this issue of Chemistry & Biology, Bok et al. show that, in
      Aspergillus nidulans, microarray analysis and manipulation of a global regulator
      can identify novel metabolite genes.

PMID- 16426965
TI  - A tighter RVxF motif makes a finer Sift.
AB  - Most partners of protein phosphatase 1 rely on an instance of the so-called RVxF
      motif for interaction with the enzyme. In this issue of Chemistry & Biology, a
      stringent definition of the motif targeting high-affinity instances enabled
      Meiselbach and colleagues to recognize novel binding partners with high
      specificity .

PMID- 16426966
TI  - Specific probes for chemokine receptors.
AB  - Chemokine receptors have attracted a good deal of public attention as important
      therapeutic targets for many diseases and disorders. In this issue of Chemistry &
      Biology, Kumar and colleagues propose a new concept of synthetic modular
      modifications to generate unnatural chemokines, which exhibit high receptor
      selectivity .

PMID- 16426967
TI  - Conditional control of protein function.
AB  - Deciphering the myriad ways in which proteins interact with each other to give
      rise to complex behaviors that define living systems is a significant challenge.
      Using perturbations of DNA, genetic analyses have provided many insights into the
      functions of proteins encoded by specific genes. However, it can be difficult to
      study essential genes using these approaches, and many biological processes occur
      on a fast timescale that precludes study using genetic methods. For these reasons
      and others, it is often desirable to target proteins directly rather than the
      genes that encode them. Over the past 20 years, several methods to regulate
      protein function have been developed. In this review, we discuss the genesis and
      use of these methods, with particular emphasis on the elements of specificity,
      speed, and reversibility.

PMID- 16426968
TI  - Peroxisome proliferator-activated receptor alpha antagonism inhibits hepatitis C
      virus replication.
AB  - Hepatitis C virus (HCV) is a global health problem and a leading cause of liver
      disease. Here, we demonstrate that the replication of HCV replicon RNA in Huh-7
      cells is inhibited by a peroxisome proliferator-activated receptor (PPAR)
      antagonist, 2-chloro-5-nitro-N-(pyridyl)benzamide (BA). Downregulation of
      PPARgamma with RNA interference approaches had no effect on HCV replication in
      Huh-7 cells, whereas PPARalpha downregulation inhibited HCV replication.
      Fluorescence and coherent anti-Stokes Raman scattering (CARS) microscopy
      demonstrate a clear buildup of lipids upon treatment with BA. These observations
      are consistent with the misregulation of lipid metabolism, phospholipid
      secretion, cholesterol catabolism, and triglyceride clearance events associated
      with the inhibition of PPARalpha. The inhibition of HCV replication by BA may
      result from disrupting lipidation of host proteins associated with the HCV
      replication complex or, more generally, by disrupting the membranous web where
      HCV replicates.

PMID- 16426969
TI  - Genomic mining for Aspergillus natural products.
AB  - The genus Aspergillus is renowned for its ability to produce a myriad of
      bioactive secondary metabolites. Although the propensity of biosynthetic genes to
      form contiguous clusters greatly facilitates assignment of putative secondary
      metabolite genes in the completed Aspergillus genomes, such analysis cannot
      predict gene expression and, ultimately, product formation. To circumvent this
      deficiency, we have examined Aspergillus nidulans microarrays for expressed
      secondary metabolite gene clusters by using the transcriptional regulator LaeA.
      Deletion or overexpression of laeA clearly identified numerous secondary
      metabolite clusters. A gene deletion in one of the clusters eliminated the
      production of the antitumor compound terrequinone A, a metabolite not described,
      from A. nidulans. In this paper, we highlight that LaeA-based genome mining helps
      decipher the secondary metabolome of Aspergilli and provides an unparalleled view
      to assess secondary metabolism gene regulation.

PMID- 16426970
TI  - The acylation state of mycobacterial lipomannans modulates innate immunity
      response through toll-like receptor 2.
AB  - Detection of Mycobacterium tuberculosis antigens by professional phagocytes via
      toll-like receptors (TLR) contributes to controlling chronic M. tuberculosis
      infection. Lipomannans (LM), which are major lipoglycans of the mycobacterial
      envelope, were recently described as agonists of TLR2 with potent activity on
      proinflammatory cytokine regulation. LM correspond to a heterogeneous population
      of acyl- and glyco-forms. We report here the purification and the complete
      structural characterization of four LM acyl-forms from Mycobacterium bovis BCG
      using MALDI MS and 2D (1)H-(31)P NMR analyses. All this biochemical work provided
      the tools to investigate the implication of LM acylation degree on its
      proinflammatory activity. The latter was ascribed to the triacylated LM form,
      essentially an agonist of TLR2, using TLR2/TLR1 heterodimers for signaling.
      Altogether, these findings shed more light on the molecular basis of LM
      recognition by TLR.

PMID- 16426971
TI  - Structural analysis of the protein phosphatase 1 docking motif: molecular
      description of binding specificities identifies interacting proteins.
AB  - The interplay between kinases and phosphatases represents a fundamental
      regulatory mechanism in biological systems. Being less numerous than kinases,
      phosphatases increase their diversity by the acquisition of a variety of binding
      partners, thereby forming a large number of holoenzymes. Proteins interacting
      with protein phosphatase 1 (PP1) often bind via a so-called docking motif to
      regulate its enzymatic activity, substrate specificity, and subcellular
      localization. Here, we systematically determined structural elements that mediate
      the binding specificity of PP1 interacting proteins, and propose a refined
      consensus sequence for high-affinity PP1 ligands. Applying this pattern to
      database searches, we predicted and experimentally confirmed several previously
      unknown PP1 interactors. Thus, the suggested PP1 docking motif enables a highly
      specific prediction of PP1 binding partners, thereby facilitating the genome-wide
      identification of PP1 interactors.

PMID- 16426972
TI  - Light-activated destruction of cancer cell nuclei by platinum diazide complexes.
AB  - A possible way to avoid dose-limiting side effects of platinum anticancer drugs
      is to employ light to cause photochemical changes in nontoxic platinum prodrugs
      that release active antitumor agents. This strategy could be used in the
      treatment of localized cancers accessible to irradiation (e.g., bladder, lung,
      esophagus, and skin). We report here that nontoxic photolabile diam(m)ino
      platinum(IV) diazido complexes inhibit the growth of human bladder cancer cells
      upon irradiation with light, and are non-crossresistant to cisplatin. Their rate
      of photolysis closely parallels that of DNA platination, indicating that the
      photolysis products interact directly, and rapidly, with DNA. Photoactivation
      results in a dramatic shrinking of the cancer cells, loss of adhesion, packing of
      nuclear material, and eventual disintegration of their nuclei, indicating a
      different mechanism of action from cisplatin.

PMID- 16426973
TI  - SMM-chemokines: a class of unnatural synthetic molecules as chemical probes of
      chemokine receptor biology and leads for therapeutic development.
AB  - Chemokines and their receptors play important roles in numerous physiological and
      pathological processes. To develop natural chemokines into receptor probes and
      inhibitors of pathological processes, the lack of chemokine-receptor selectivity
      must be overcome. Here, we apply chemical synthesis and the concept of modular
      modifications to generate unnatural synthetically and modularly modified (SMM)
      chemokines that have high receptor selectivity and affinity, and reduced
      toxicity. A proof of the concept was shown by transforming the nonselective viral
      macrophage inflammatory protein-II into new analogs with enhanced selectivity and
      potency for CXCR4 or CCR5, two principal coreceptors for human immunodeficiency
      virus (HIV)-1 entry. These new analogs provided insights into receptor binding
      and signaling mechanisms and acted as potent HIV-1 inhibitors. These results
      support the concept of SMM-chemokines for studying and controlling the function
      of other chemokine receptors.

PMID- 16426974
TI  - Target structure-based discovery of small molecules that block human p53 and CREB
      binding protein association.
AB  - Lysine acetylation of human tumor suppressor p53 in response to cellular stress
      signals is required for its function as a transcription factor that regulates
      cell cycle arrest, senescence, or apoptosis. Here, we report small molecules that
      block lysine 382-acetylated p53 association with the bromodomain of the
      coactivator CBP, an interaction essential for p53-induced transcription of the
      cell cycle inhibitor p21 in response to DNA damage. These chemicals were
      discovered in target structure-guided nuclear magnetic resonance spectroscopy
      screening of a focused chemical library constructed based on the structural
      knowledge of CBP bromodomain/p53-AcK382 binding. Structural characterization
      shows that these chemicals inhibit CBP/p53 association by binding to the acetyl
      lysine binding site of the bromodomain. Cell-based functional assays demonstrate
      that the lead chemicals can modulate p53 stability and function in response to
      DNA damage.

PMID- 16426975
TI  - Engineering cotton (+)-delta-cadinene synthase to an altered function: germacrene
      D-4-ol synthase.
AB  - The combined approaches of rational design and random mutagenesis were applied to
      generate a sesquiterpene synthase with an altered activity. Due to the lack of a
      convenient screen for sesquiterpene synthase activity, a high-throughput dual
      activity screen was used by fusing (+)-delta-cadinene synthase to chloramphenicol
      acetyltransferase (CAT). The gene encoding (+)-delta-cadinene synthase was
      mutagenized using error-prone PCR. The resulting mutant fusion proteins were
      screened for CAT activity and altered sesquiterpene selectivity. Twenty-one
      clones producing (+)-delta-cadinene and germacrene D-4-ol in different ratios
      were isolated from the library. Analysis using a homology model of (+)-delta
      cadinene synthase suggested that the G helix plays a very important role in (+)
      delta-cadinene formation. Reconstruction of the G helix using site-directed,
      saturation mutagenesis yielded a mutant, N403P/L405H, that maintained its
      specific activity and showed higher selectivity to germacrene D-4-ol in vivo (up
      to 93%).

PMID- 16426976
TI  - Rapamycin analogs with differential binding specificity permit orthogonal control
      of protein activity.
AB  - Controlling protein dimerization with small molecules has broad application to
      the study of protein function. Rapamycin has two binding surfaces: one that binds
      to FKBP12 and the other to the Frb domain of mTor/FRAP, directing their
      dimerization. Rapamycin is a potent cell growth inhibitor, but chemical
      modification of the surface contacting Frb alleviates this effect. Productive
      interactions with Frb-fused proteins can be restored by mutation of Frb to
      accommodate the rapamycin analog (a rapalog). We have quantitatively assessed the
      interaction between rapalogs functionalized at C16 and C20 and a panel of Frb
      mutants. Several drug-Frb mutant combinations have different and nonoverlapping
      specificities. These Frb-rapalog partners permit the selective control of
      different Frb fusion proteins without crossreaction. The orthogonal control of
      multiple target proteins broadens the capabilities of chemical induction of
      dimerization to regulate biologic processes.

PMID- 16426978
TI  - A critical investigation of ISO 11948-2 and ISO 11948-1 for predicting the
      leakage performance of small disposable incontinence pads for lightly incontinent
      women.
AB  - ISO 11948-2--an international standard laboratory method developed to predict the
      leakage performance of small disposable pads for lightly incontinent women--was
      investigated. The repeatability and reproducibility (precision within and between
      laboratories, respectively) of two variants on the method were found to be poor.
      The coefficient of variation for each method variant in each laboratory (two
      laboratories ran each variant) was higher than 40% for about half the 12 products
      evaluated. Results differed by up to 94% between laboratories for a given
      product. The ability of the method to predict the leakage performance of pads was
      investigated by measuring correlations between the clinical evaluations of the 12
      products, and technical evaluations using ISO 11948-2. Correlations were very
      weak (r < or= 0.487). Accordingly, it is recommended that 11948-2 is withdrawn. A
      second international standard method (ISO 11948-1)--developed for evaluating
      large pads, but sometimes used on small ones--was also investigated. Correlations
      between the clinical evaluations of the 12 products and technical evaluations
      using ISO 11948-1 were weak (r < or = 0.560). Accordingly, it is recommended that
      ISO 11948-1 is not used for evaluating small disposable bodyworn pads for women.

PMID- 16426979
TI  - Finite element analysis of the lumbar spine with a new cage using a topology
      optimization method.
AB  - In recent years, degenerative spinal instability has been effectively treated
      with a cage. However, little attention is focused on the design concept of the
      cage. The purpose of this study was to develop a new cage and evaluate its
      biomechanical function using a finite element method (FEM). This study employed
      topology optimization to design a new cage and analyze stress distribution of the
      lumbar spine from L1 to L3 with a new cage by using the commercial software ANSYS
      6.0. A total of three finite element models, namely the intact lumbar spine, the
      spine with double RF cages, and with double new cages, were established. The
      loading conditions were that 10Nm flexion, extension, lateral bending, and
      torsion, respectively, were imposed on the superior surface of the L1 vertebral
      body. The bottom of the L3 vertebral body was constrained completely. The FEM
      estimated that the new cage not only could be reduced to 36% of the volume of the
      present RF cage but was also similar in biomechanical performance such as range
      of motion, stress of adjacent disc, and lower subsidence to the RF cage. The
      advantage of the new cage was that the increased space allowed more bone graft to
      be placed and the cage saved material. The disadvantage was that stress of the
      new cage was greater than that of the RF cage.

PMID- 16426980
TI  - NICE to see the bigger picture.

PMID- 16426981
TI  - Pneumococcal meningitis: a 21st century perspective.

PMID- 16426983
TI  - Epilepsy, suicidal behaviour, and depression: do they share common pathogenic
      mechanisms?

PMID- 16426982
TI  - Evidence-based care in amyotrophic lateral sclerosis.

PMID- 16426984
TI  - Our eyes: windows to our souls or crystal balls?

PMID- 16426985
TI  - OSMS is NMO, but not MS: proven clinically and pathologically.

PMID- 16426986
TI  - Towards individualised multiple sclerosis treatment.

PMID- 16426987
TI  - The neuroanatomy of very remote memory.

PMID- 16426988
TI  - Clinical features, complications, and outcome in adults with pneumococcal
      meningitis: a prospective case series.
AB  - BACKGROUND: Bacterial meningitis is a grave disease of high incidence, especially
      in less developed countries. Here, we describe its clinical presentation,
      spectrum of complications, prognostic factors, and outcome in adults with
      pneumococcal meningitis. METHODS: From October, 1998, to April, 2002, we assessed
      352 episodes of community-acquired pneumococcal meningitis, confirmed by culture
      of cerebrospinal fluid (CSF), which occurred in patients older than 16 years.
      Predictors for an unfavourable outcome (Glasgow outcome scale score 1-4) were
      identified by logistic regression with multiple imputation techniques. FINDINGS:
      245 (70%) episodes of pneumococcal meningitis were associated with an underlying
      disorder. Cranial CT was done for 85% of episodes and revealed underlying
      disorders in 17% (50/299) and meningitis-associated intracranial complications in
      39% (117/299). Independent predictors for an unfavourable outcome were a low
      score on the Glasgow coma scale, cranial nerve palsies, a raised erythrocyte
      sedimentation rate, a CSF leucocyte count less than 1000 cells per mm(3), and a
      high CSF protein concentration on admission. Overall in-hospital mortality was
      30%. Prevalence of neurological and systemic complications did not differ between
      patients aged younger than 60 years and those aged 60 years and older; however,
      systemic complications were the cause of death in 59% (32/54) of fatal episodes
      in patients aged 60 years and older, whereas neurological complications were the
      cause of death in 65% (20/31) of fatal episodes in younger patients.
      INTERPRETATION: Pneumococcal meningitis is associated with high mortality and
      morbidity rates in adults. Whereas neurological complications are the leading
      cause of death in younger patients, elderly patients die predominantly from
      systemic complications.

PMID- 16426989
TI  - Ethnic disparities in incidence of stroke subtypes: Auckland Regional Community
      Stroke Study, 2002-2003.
AB  - BACKGROUND: Limited population-based data exist on differences in the incidence
      of major pathological stroke types and ischaemic stroke subtypes across ethnic
      groups. We aimed to provide such data within the large multi-ethnic population of
      Auckland, New Zealand. METHODS: All first-ever cases of stroke (n=1423) in a
      population-based register in 940 000 residents (aged 15 years) in Auckland, New
      Zealand, for a 12-month period in 2002-2003, were classified into ischaemic
      stroke, primary intracerebral haemorrhage (PICH), subarachnoid haemorrhage, and
      undetermined stroke, according to standard definitions and results of
      neuroimaging/necropsy (in over 90% of cases). Ischaemic stroke was further
      classified into five subtypes. Ethnicity was self-identified and grouped as New
      Zealand (NZ)/European, Maori/Pacific, and Asian/other. Incidence rates were
      standardised to the WHO world population by the direct method, and differences in
      rates between ethnic groups expressed as rate ratios (RRs), with NZ/European as
      the reference group. FINDINGS: In NZ/European people, ischaemic stroke comprised
      73%, PICH 11%, and subarachnoid haemorrhage 6%, but PICH was higher in
      Maori/Pacific people (17%) and in Asian/other people (22%). Compared with
      NZ/European people, age-adjusted RRs for PICH were 2.7 (95% CI 1.8-4.0) and 2.3
      (95% CI 1.4-3.7) among Maori/Pacific and Asian/other people, respectively. The
      corresponding RR for ischaemic stroke was greater for Maori/Pacific people (1.7
      [95% CI 1.4-2.0]), particularly embolic stroke, and for Asian/other people (1.3
      [95% CI 1.0-1.7]). The onset of stroke in Maori/Pacific and Asian/other people
      began at significantly younger ages (62 years and 64 years, respectively) than in
      NZ/Europeans (75 years; p<0.0001). There were ethnic differences in the risk
      factor profiles (such as age, sex, hypertension, cardiac disease, diabetes,
      hypercholesterolaemia, smoking status, overweight) for the stroke types and
      subtypes. INTERPRETATION: Compared to NZ/Europeans, Maori/Pacific and Asian/other
      people are at higher risk of ischaemic stroke and PICH, whereas similar rates of
      subarachnoid haemorrhage were evident across ethnic groups. The ethnic
      disparities in the rates of stroke types could be due to substantial differences
      found in risk factor profiles between ethnic groups. This information should be
      considered when planning prevention and stroke-care services in multi-ethnic
      communities.

PMID- 16426990
TI  - Effects of non-invasive ventilation on survival and quality of life in patients
      with amyotrophic lateral sclerosis: a randomised controlled trial.
AB  - BACKGROUND: Few patients with amyotrophic lateral sclerosis currently receive non
      invasive ventilation (NIV), reflecting clinical uncertainty about the role of
      this intervention. We aimed to assess the effect of NIV on quality of life and
      survival in amyotrophic lateral sclerosis in a randomised controlled trial.
      METHODS: 92 of 102 eligible patients participated. They were assessed every 2
      months and randomly assigned to NIV (n=22) or standard care (n=19) when they
      developed either orthopnoea with maximum inspiratory pressure less than 60% of
      that predicted or symptomatic hypercapnia. Primary validated quality-of-life
      outcome measures were the short form 36 mental component summary (MCS) and the
      sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained
      above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and
      microsym) were measured. FINDINGS: NIV improved T(i)MCS, T(i)sym, microMCS,
      microsym, and survival in all patients and in the subgroup with better bulbar
      function (n=20). This subgroup showed improvement in several measures of quality
      of life and a median survival benefit of 205 days (p=0.006) with maintained
      quality of life for most of this period. NIV improved some quality-of-life
      indices in those with poor bulbar function, including microsym (p=0.018), but
      conferred no survival benefit. INTERPRETATION: In patients with amyotrophic
      lateral sclerosis without severe bulbar dysfunction, NIV improves survival with
      maintenance of, and improvement in, quality of life. The survival benefit from
      NIV in this group is much greater than that from currently available
      neuroprotective therapy. In patients with severe bulbar impairment, NIV improves
      sleep-related symptoms, but is unlikely to confer a large survival advantage.

PMID- 16426992
TI  - The measurement and clinical relevance of brain atrophy in multiple sclerosis.
AB  - Brain atrophy has emerged as a clinically relevant component of disease
      progression in multiple sclerosis. Progressive loss of brain tissue bulk can be
      detected in vivo in a sensitive and reproducible manner by MRI. Clinical studies
      have shown that brain atrophy begins early in the disease course. The increasing
      amount of data linking brain atrophy to clinical impairments suggest that
      irreversible tissue destruction is an important determinant of disease
      progression to a greater extent than can be explained by conventional lesion
      assessments. In this review, we will summarise the proposed mechanisms
      contributing to brain atrophy in patients with multiple sclerosis. We will
      critically discuss the wide range of MRI-based methods used to quantify regional
      and whole-brain-volume loss. Based on a review of current information, we will
      summarise the rate of atrophy among phenotypes for multiple sclerosis, the
      clinical relevance of brain atrophy, and the effect of disease-modifying
      treatments on its progression.

PMID- 16426993
TI  - Seizure versus syncope.
AB  - One of the most common but difficult management problems in medicine is that of
      patients who present with a paroxysmal loss of consciousness. All too often the
      underlying diagnosis remains elusive. This has a cost both in terms of mortality
      and ongoing morbidity and in terms of the financial burden associated with
      hospitalisation and repeated investigations. We describe a practical approach to
      this clinical dilemma, which is rooted in adherence to basic principles of
      history taking and examination, formulation of a reasonable differential
      diagnosis, followed by an intelligent use of specific investigations and
      selection of an appropriate treatment. We also discuss the effect of sudden
      unexpected death in epilepsy and sudden cardiac death. Despite a careful and
      thorough approach to the patient with a "seizure versus syncope" problem, many
      will require repeated assessment before a diagnosis is made.

PMID- 16426991
TI  - Chronic disorders with episodic manifestations: focus on epilepsy and migraine.
AB  - Epilepsy and migraine are chronic neurological disorders with episodic
      manifestations that are commonly treated in neurological practice and frequently
      occur together. In this review we examine similarities and contrasts between
      these disorders, with focus on epidemiology and classification, temporal
      coincidence, triggers, and mechanistically based therapeutic overlap. This
      investigation draws attention to unique aspects of both epilepsy and migraine,
      while identifying areas of crossover in which each specialty could benefit from
      the experience of the other.

PMID- 16426994
TI  - Socioeconomic status and stroke.
AB  - This paper reviews the current evidence for the association between socioeconomic
      status and stroke incidence, survival, mortality, and other outcomes. The
      evidence is strongest for mortality and incidence of stroke, with high rates of
      stroke in low socioeconomic groups being a consistent finding. Low socioeconomic
      groups also have lower survival and greater stroke severity than high
      socioeconomic groups, although there is less evidence for this association. The
      mechanisms through which socioeconomic status affects stroke risk and outcomes
      are unclear but some studies report that differences in risk-factor prevalence
      could account for some of the variation. We discuss the implications of these
      findings and make recommendations for future research. Studies using prospective
      population-based methods with improved control for confounding factors are needed
      to confirm or refute these associations. Understanding the causal associations
      between socioeconomic status and stroke will allow interventions to be
      appropriately targeted and assessed.

PMID- 16426995
TI  - Update on pharmacogenetics in epilepsy: a brief review.
AB  - Recent developments in the pharmacogenetics of antiepileptic drugs provide new
      prospects for predicting the efficacy of treatment and potential side-effects.
      Epilepsy is a common, serious, and treatable neurological disorder, yet current
      treatment is limited by high rates of adverse drug reactions and lack of complete
      seizure control in a significant proportion of patients. The disorder is
      especially suitable for pharmacogenetic investigation because treatment response
      can be quantified and side-effects can be assessed with validated measures.
      Additionally, there is substantial knowledge of the pharmacodynamics and kinetics
      of antiepileptic drugs, and some candidate genes implicated in the disorder have
      been identified. However, recent studies of the association of particular genes
      and their genetic variants with seizure control and adverse drug reactions have
      not provided unifying conclusions. This article reviews the published work and
      summarises the state of research in this area. Future directions for research and
      the application of this technology to the clinical practice of individualising
      treatment for epilepsy are discussed.

PMID- 16426997
TI  - Calcium channels as therapeutic targets in neuropathic pain.
AB  - Injury to the nerve can produce changes in dorsal horn function and pain. This
      facilitated processing may be mediated in part by voltage-sensitive calcium
      channels. Activation of these channels increases intracellular calcium, thereby
      mediating transmitter release and activating cascades serving to alter membrane
      excitability and initiate protein transcription. Molecular techniques reveal the
      complexity and multiplicity of these channels. At the spinal level, blocking of
      several of these calcium channels, notably those of the N type, can prominently
      alter pain behavior. These effects are consistent with the high levels of
      expression on primary afferents and dorsal horn neurons of these channels. More
      recently, agents binding to auxiliary subunits such as the alpha2delta of these
      calcium channels diminish excitability of the membrane without completely
      blocking channel function. Drugs that bind to this site, highly expressed in the
      superficial dorsal horn, will diminish neuropathic pain states. Continuing
      developments in our understanding of these channel functions promises to advance
      the control of aberrant spinal functions initiated by nerve injury. PERSPECTIVE:
      Pharmacologic studies showing the role of spinal voltage-sensitive calcium
      channels in neuropathic pain models provide evidence suggesting their
      applicability in human pain states.

PMID- 16426998
TI  - Sodium channels and mechanisms of neuropathic pain.
AB  - Na+ channels are large transmembrane proteins with a voltage-gated central pore
      capable of selectively passing Na+ ions. They are critical determinants of the
      electrical excitability of sensory neurons and play a key role in pain sensation
      by controlling afferent impulse discharge. Injury and disease affecting
      peripheral nerves induces axonopathy and demyelination. These neuropathic
      changes, in turn, trigger membrane remodeling in injured afferents and perhaps
      also in uninjured neighbors. A major consequence of the remodeling is increased
      cellular excitability. This is due in large part to subtype-selective
      abnormalities in the expression and trafficking of Na+ channels and perhaps also
      to altered kinetic properties of unitary channels. Hyperexcitable neurons show
      enhanced membrane resonance, rhythmogenesis, and ectopic spiking. The resulting
      excess discharge constitutes a primary neuropathic pain signal. In addition, it
      triggers and maintains central sensitization. This amplifies residual afferent
      input, yielding tactile allodynia, and it also amplifies ongoing ectopia that
      exaggerates spontaneous pain. Membrane-stabilizing Na+ channel ligands suppress
      neuropathic pain by selectively reducing membrane resonance in injured afferents
      and hence ectopic hyperexcitability. The clinical usefulness of these
      peripherally acting drugs might be enhanced by reducing their central side
      effects. PERSPECTIVE: Neuropathic pain is a complex outcome of multiple
      pathophysiological changes that develop in the peripheral nervous system (PNS)
      and the central nervous system (CNS) following nerve injury or disease. All or
      most of the CNS changes are thought to be due to abnormal signaling from the PNS,
      notably electrical hyperexcitability of peripheral sensory neurons. Because
      hyperexcitability is associated with abnormal sodium channel regulation, this
      process is a prime target for therapeutic intervention.

PMID- 16426999
TI  - Translating basic research on sodium channels in human neuropathic pain.
AB  - A number of experimental studies in animals have suggested that voltage-gated
      sodium channels may play a crucial role in neuropathic pain. However, it is still
      difficult to translate the pathophysiological mechanisms identified in animal
      studies to the clinic and several questions regarding the role of sodium channels
      in neuropathic pain must therefore be addressed primarily in the clinical
      setting. Despite providing indirect information, pharmacologic challenge using
      sodium channel blockers, such as some antiepileptics, local anesthetics and
      derivatives, is the best way to investigate the role of sodium channels in the
      various clinical symptoms of neuropathies (eg, spontaneous pain, mechanical or
      thermal allodynia, and hyperalgesia). Randomized controlled trials have
      demonstrated the efficacy of these compounds for various neuropathic pain
      conditions. Recent psychophysical studies in which symptoms and signs are more
      accurately assessed indicate that these compounds act as antihyperalgesic agents
      rather than as simple analgesics. They also show that the sensitivity to these
      drugs is not affected by the aetiology of pain and the peripheral or central
      location of the nerve lesion. These data emphasize the role of peripheral and
      central sodium channels in neuropathic pain. Studies using more selective sodium
      channel blockers are required to gain further insight into the role of the
      various subtypes of sodium channel in these pain conditions. PERSPECTIVE:
      Pharmacological challenge using sodium channel blockers is the best way to
      translate basic research on sodium channels in human neuropathic pain. To date,
      the role of sodium channels in neuropathic pain symptoms/signs is mostly
      documented for mechanical static and dynamic allodynia, and either peripheral or
      central sodium channels may be involved.

PMID- 16427000
TI  - Ion channel targets and treatment efficacy in neuropathic pain.
AB  - Chronic neuropathic pain due to injury or dysfunction of the nervous system
      remains a formidable treatment challenge in spite of a growing range of
      medication choices. We review current clinical research supporting the use of ion
      channel modulators for neuropathic pain states. New modes of local drug delivery,
      novel Ca2+ channel targets, and increased choices for drugs with activity at
      Na+channels are transforming this longstanding therapeutic strategy. Clinical
      decision making is increasingly informed by a more nuanced understanding of the
      role of voltage-gated Na+channels (VGSCs) and Ca2+ channels (VGCCs) in the
      pathophysiology of nerve injury. Although holding great promise for the future,
      mechanism-based approaches to treatment will require greater understanding of the
      analgesic mechanisms of drug action and of the relationships between
      pathophysiologic mechanisms and clinical presentation. PERSPECTIVE: Treatment
      options for neuropathic pain targeting ion channels have grown rapidly in the
      past decade. An evolving body of clinical research supports the widespread use of
      this longstanding therapeutic strategy. Improved efficacy of ion channel
      modulators hinges upon further elucidation of the relationship between signs and
      symptoms of pain and underlying pathophysiology.

PMID- 16427002
TI  - Getting a grip on licensing: mechanism of stable Mcm2-7 loading onto replication
      origins.
AB  - A recent Molecular Cell paper by Randell et al. (2006) sheds light on the role of
      ATP hydrolysis by Cdc6 in promoting the stable loading of the Mcm2-7 complex onto
      origins of DNA replication.

PMID- 16427003
TI  - Modified view of tRNA: stability amid sequence diversity.
AB  - In a recent issue of Molecular Cell, a report from the Phizicky lab challenges
      two commonly held notions regarding tRNAs: (1) tRNAs are stable molecules
      shielded from the machinery that cause other RNAs to have short half-lives, and
      (2) the many modifications found on tRNAs serve only subtle biological functions.
      Alexandrov et al. (2006) show that tRNA modifications can play an important role
      in tRNA stability, as without particular modifications, tRNA half-life can be
      reduced from hours to minutes by a new turnover pathway.

PMID- 16427004
TI  - Chaperoning through the mitochondrial intermembrane space.
AB  - The first high-resolution structure of a mitochondrial translocase complex, the
      Tim9-Tim10 chaperone, is reported by Webb et al. (2006) in a recent issue of
      Molecular Cell, providing important insight in the transport of hydrophobic
      proteins through the aqueous intermembrane space and the mechanisms of protein
      assembly.

PMID- 16427005
TI  - The La protein-RNA complex surfaces.
AB  - A recent issue of Molecular Cell reported that the typical nucleic acid binding
      surfaces of the RRM and winged-helix motifs, although present in the RNA binding
      protein La, are not used to engage its best-characterized ligand, 3' UUU-OH.
      Instead, La uses edgewise and backsides of these motifs for UUU-OH recognition,
      leaving open their typical surfaces for other potential interactions. These
      observations provide a framework for appreciating the various activities
      attributed to this ubiquitous nuclear phosphoprotein, which include its principal
      function, snRNA 3' end protection, in addition to mRNA-related and RNA chaperone
      like activities, as well as DNA and chromatin-associated activity.

PMID- 16427006
TI  - The control mechanism for lagging strand polymerase recycling during
      bacteriophage T4 DNA replication.
AB  - Given the polarity of DNA duplex, replication by the leading strand polymerase is
      continuous whereas that by the lagging strand polymerase is discontinuous
      proceeding through Okazaki fragments. Yet the respective polymerases act
      processively, implying that the recycling of the lagging strand polymerase is a
      controlled process. We demonstrate that the rate of the lagging strand polymerase
      relative to that of fork movement affects Okazaki fragment size and generates
      ssDNA gaps. We show by using a substrate with limited priming sites that Okazaki
      fragments can be shifted to shorter lengths by varying the rate of the primase.
      We find that clamp and clamp loader levels affect both primer utilization and
      Okazaki fragment size, possibly implicating clamp loading onto the RNA primer in
      the mechanism of lagging strand polymerase recycling. We formulate a signaling
      model capable of rationalizing the distribution of Okazaki fragments under
      various conditions for this and possibly other replisomes.

PMID- 16427007
TI  - DNA-induced switch from independent to sequential dTTP hydrolysis in the
      bacteriophage T7 DNA helicase.
AB  - We show that the mechanisms of DNA-dependent and -independent dTTP hydrolysis by
      the gene 4 protein of bacteriophage T7 differ in the pathways by which these
      reactions are catalyzed. In the presence of dTTP, gene 4 protein monomers
      assemble as a ring that binds single-stranded DNA and couples the hydrolysis of
      dTTP to unidirectional translocation and the unwinding of duplex DNA. When mixing
      wild-type monomers with monomers lacking the catalytic base for the dTTPase
      reaction, we observe that each wild-type subunit hydrolyzes dTTP independently in
      the absence of single-stranded DNA. Conversely, when either these catalytically
      inactive monomers or altered monomers incapable of binding single-stranded DNA
      are mixed with wild-type monomers, a small fraction of altered to wild-type
      monomers causes a sharp decline in DNA-dependent dTTP hydrolysis. We propose that
      sequential hydrolysis of dTTP is coupled to the transfer of single-stranded DNA
      from subunit to adjacent subunit.

PMID- 16427008
TI  - Opening closed arms: long-distance activation of SMC ATPase by hinge-DNA
      interactions.
AB  - Structural maintenance of chromosomes (SMC) proteins form a V-shaped dimer in
      which a central hinge domain connects two coiled-coil arms, each having an ATP
      binding head domain at its distal end. Here, we show that the hinge domain plays
      essential roles in modulating the mechanochemical cycle of SMC proteins. An
      initial interaction of the hinge domain with DNA leads to opening of the arms by
      triggering hydrolysis of ATP bound to the head domains, which are located
      approximately 50 nm away from the hinge. This conformational change allows the
      inner surface of the hinge domain to stably interact with DNA by an ATP
      independent mechanism and primes ATP-driven engagement between the liberated head
      domains either intramolecularly or intermolecularly. Consistently, a variety of
      hinge mutations drastically alter DNA binding properties of SMC proteins through
      distinct mechanisms. Our results suggest that SMC proteins possess an intrinsic
      property to change their own conformations upon binding to DNA.

PMID- 16427009
TI  - MDC1 maintains genomic stability by participating in the amplification of ATM
      dependent DNA damage signals.
AB  - MDC1 functions in checkpoint activation and DNA repair following DNA damage. To
      address the physiological role of MDC1, we disrupted the MDC1 gene in mice. MDC1
      /- mice recapitulated many phenotypes of H2AX-/- mice, including growth
      retardation, male infertility, immune defects, chromosome instability, DNA repair
      defects, and radiation sensitivity. At the molecular level, H2AX, MDC1, and ATM
      form a positive feedback loop, with MDC1 directly mediating the interaction
      between H2AX and ATM. MDC1 binds phosphorylated H2AX through its BRCT domain and
      ATM through its FHA domain. Through these interactions, MDC1 accumulates
      activated ATM flanking the sites of DNA damage, facilitating further ATM
      dependent phosphorylation of H2AX and the amplification of DNA damage signals. In
      the absence of MDC1, many downstream ATM signaling events are defective. These
      results suggest that MDC1, as a signal amplifier of the ATM pathway, is vital in
      controlling proper DNA damage response and maintaining genomic stability.

PMID- 16427010
TI  - H2AX prevents DNA breaks from progressing to chromosome breaks and
      translocations.
AB  - Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin
      heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires
      activation-induced cytidine deaminase (AID) and involves joining of DSB
      intermediates by end joining. We find that AID-dependent IgH locus chromosome
      breaks occur at high frequency in primary H2AX-deficient B cells activated for
      CSR and that a substantial proportion of these breaks participate in chromosomal
      translocations. Moreover, activated B cells deficient for ATM, 53BP1, or MDC1,
      which interact with H2AX during the DSB response, show similarly increased IgH
      locus breaks and translocations. Thus, our findings implicate a general role for
      these factors in promoting end joining and thereby preventing DSBs from
      progressing into chromosomal breaks and translocations. As cellular p53 status
      does not markedly influence the frequency of such events, our results also have
      implications for how p53 and the DSB response machinery cooperate to suppress
      generation of lymphomas with oncogenic translocations.

PMID- 16427011
TI  - p8/TTD-A as a repair-specific TFIIH subunit.
AB  - How subunits of the transcription/repair factor TFIIH cooperate to allow for the
      removal of DNA lesions or for the transcription of genes is crucial to understand
      the functioning of this complex. Here, we reveal that p8/TTD-A, the tenth subunit
      of TFIIH, has a critical role in DNA repair where it triggers DNA opening by
      stimulating XPB ATPase activity together with the damage recognition factor XPC
      hHR23B. Fluorescent antibody labeling shows that such opening is needed for the
      recruitment of XPA to the site of the damage. By contrast, p8 is dispensable for
      RNA synthesis and doesn't interfere with the transcriptional function of CAK,
      although both interact with the XPD subunit. Interestingly, p8 overexpression in
      TTD-XPD cells counteracts the detrimental effect of XPD mutations by restoring
      the cellular TFIIH concentration. These findings resolve the primary functions of
      p8 and unveil how TFIIH components specifically direct the complex toward repair
      or transcription.

PMID- 16427012
TI  - P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for
      processive transcription elongation.
AB  - Human DSIF, a heterodimer composed of hSpt4 and hSpt5, plays opposing roles in
      transcription elongation by RNA polymerase II (RNA Pol II). Here, we describe an
      evolutionarily conserved repetitive heptapeptide motif (consensus = G-S-R/Q-T-P)
      in the C-terminal region (CTR) of hSpt5, which, like the C-terminal domain (CTD)
      of RNA Pol II, is highly phosphorylated by P-TEFb. Thr-4 residues of the CTR
      repeats are functionally important phosphorylation sites. In vitro, Thr-4
      phosphorylation is critical for the elongation activation activity of DSIF, but
      not to its elongation repression activity. In vivo, Thr-4 phosphorylation is
      critical for epidermal growth factor (EGF)-inducible transcription of c-fos and
      for efficient progression of RNA Pol II along the gene. We consider this
      phosphorylation to be a switch that converts DSIF from a repressor to an
      activator. We propose the "mini-CTD" hypothesis, in which phosphorylated CTR is
      thought to function in a manner analogous to phosphorylated CTD, serving as an
      additional code for active elongation complexes.

PMID- 16427013
TI  - Nrd1 interacts with the nuclear exosome for 3' processing of RNA polymerase II
      transcripts.
AB  - The exosome complex is involved in multiple RNA processing and degradation
      pathways. How exosome is recruited to particular RNA substrates and then chooses
      between RNA processing and degradation modes remains unclear. We find that the
      RNA binding protein Nrd1, complexed with its partners Nab3, Sen1, and cap binding
      complex, physically interacts with the nuclear form of exosome. Nrd1 stimulates
      the RNA degradation activity of the exosome in vitro. However, Nrd1 can also
      block 3' to 5' degradation by the exosome at some Nrd1 binding sites. Nrd1
      mutations share some phenotypes with exosome mutants, including increased
      readthrough transcription from several mRNA and sn/snoRNA genes. Therefore, Nrd1
      may recruit exosome to RNA and influence the choice between processing and
      degradation. Since Nrd1 is known to bind RNA polymerase II and be important for
      sn/snoRNA 3' end processing, Nrd1 may link transcription and RNA 3' end formation
      with surveillance by the exosome.

PMID- 16427015
TI  - Functional division of substrate processing cofactors of the ubiquitin-selective
      Cdc48 chaperone.
AB  - Ubiquitin-dependent protein degradation usually involves escort factors that
      target ubiquitylated substrates to the proteasome. A central element in a major
      escort pathway is Cdc48, a chaperone-like AAA ATPase that collects ubiquitylated
      substrates via alternative substrate-recruiting cofactors. Cdc48 also associates
      with Ufd2, an E4 multiubiquitylation enzyme that adds further ubiquitin moieties
      to preformed ubiquitin conjugates to promote degradation. Here, we show that E4
      can be counteracted in vivo by two distinct mechanisms. First, Ufd3, a WD40
      repeat protein, directly competes with Ufd2, because both factors utilize the
      same docking site on Cdc48. Second, Cdc48 also binds Otu1, a deubiquitylation
      enzyme, which disassembles multiubiquitin chains. Notably, Cdc48 can bind Otu1
      and Ufd3 simultaneously, making a cooperation of both inhibitory mechanisms
      possible. We propose that the balance between the distinct substrate-processing
      cofactors may determine whether a substrate is multiubiquitylated and routed to
      the proteasome for degradation or deubiquitylated and/or released for other
      purposes.

PMID- 16427014
TI  - Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided
      pseudouridylation and dyskeratosis congenita.
AB  - H/ACA RNA-protein complexes, comprised of four proteins and an H/ACA guide RNA,
      modify ribosomal and small nuclear RNAs. The H/ACA proteins are also essential
      components of telomerase in mammals. Cbf5 is the H/ACA protein that catalyzes
      isomerization of uridine to pseudouridine in target RNAs. Mutations in human Cbf5
      (dyskerin) lead to dyskeratosis congenita. Here, we describe the 2.1 A crystal
      structure of a specific complex of three archaeal H/ACA proteins, Cbf5, Nop10,
      and Gar1. Cbf5 displays structural properties that are unique among known
      pseudouridine synthases and are consistent with its distinct function in RNA
      guided pseudouridylation. We also describe the previously unknown structures of
      both Nop10 and Gar1 and the structural basis for their essential roles in
      pseudouridylation. By using information from related structures, we have modeled
      the entire ribonucleoprotein complex including both guide and substrate RNAs. We
      have also identified a dyskeratosis congenita mutation cluster site within a
      modeled dyskerin structure.

PMID- 16427016
TI  - Three-dimensional structure of vinculin bound to actin filaments.
AB  - Vinculin plays a pivotal role in cell adhesion and migration by providing the
      link between the actin cytoskeleton and the transmembrane receptors, integrin and
      cadherin. We used a combination of electron microscopy, computational docking,
      and biochemistry to provide an atomic model of how the vinculin tail binds actin
      filaments. The vinculin tail actin binding site comprises two distinct regions.
      One of these regions is exposed in the full-length autoinhibited conformation of
      vinculin, whereas the second site is sterically occluded by vinculin's N-terminal
      domain. The partial accessibility of the F-actin binding site in the
      autoinhibited full-length vinculin structure suggests that F-actin can act as
      part of a combinatorial input framework with other binding partners such as alpha
      catenin or talin to induce vinculin head-tail dissociation, thus promoting
      vinculin activation. Furthermore, binding to F-actin potentiates a local
      rearrangement in the vinculin tail that in turn promotes vinculin dimerization
      and, hence, formation of actin bundles.

PMID- 16427017
TI  - A nitric oxide signaling pathway controls CREB-mediated gene expression in
      neurons.
AB  - Prevailing views of neurotrophin action hold that the transcription factor CREB
      is constitutively bound to target genes with transcriptional activation occurring
      via CREB phosphorylation. However, we report that within several CRE-containing
      genes, CREB is not constitutively bound. Upon exposure of neurons to brain
      derived neurotrophic factor (BDNF), CREB becomes rapidly bound to DNA coincident
      with phosphorylation at its transcriptional regulatory site, Ser133. This
      inducible CREB-DNA binding is independent of CREB Ser133 phosphorylation and is
      not affected by inhibition of the ERK or PI3K signaling pathways. Instead, BDNF
      regulates CREB binding by initiating a nitric oxide-dependent signaling pathway
      that leads to S-nitrosylation of nuclear proteins that associate with CREB target
      genes. Pharmacological manipulation of neurons in vitro and analysis of mice
      lacking neuronal nitric oxide synthase (nNOS) suggest that NO mediates BDNF and
      activity-dependent expression of CREB target genes. Thus, in conjunction with
      CREB phosphorylation, the NO pathway controls CREB-DNA binding and CRE-mediated
      gene expression.

PMID- 16427019
TI  - Attraction and distraction of attention with roadside advertisements.
AB  - The optimum positioning of roadside advertisements is recognized by the industry
      as an important factor in attracting the attention of passing drivers. Less
      acknowledged is the possibility that the location of an advertisement may
      distract attention from vital driving-related information. This study compared
      street-level advertisements (SLAs; predominantly bus shelters) with raised-level
      advertisements (RLAs) of the same size that were suspended 3 m above the ground,
      on their ability to attract attention under different task conditions.
      Participants were split into two groups and watched video clips of driving,
      rating them for hazardousness while their eye movements were recorded. One of the
      groups was additionally primed to attend to advertisements. SLAs received the
      most fixations when participants were solely looking for hazards, and the fewest
      fixations when primed to look for advertisements. Though SLAs also had longer
      fixations than the RLAs, they were more poorly recognized in a subsequent memory
      test. We conclude that SLAs attract and hold attention at inappropriate times
      compared to raised-level advertisements.

PMID- 16427018
TI  - MUC1 oncoprotein stabilizes and activates estrogen receptor alpha.
AB  - The MUC1 protein is aberrantly overexpressed by most human breast carcinomas. We
      report that the MUC1 C-terminal subunit associates with estrogen receptor alpha
      (ERalpha) and that this interaction is stimulated by 17beta-estradiol (E2). MUC1
      binds directly to the ERalpha DNA binding domain and stabilizes ERalpha by
      blocking its ubiquitination and degradation. Chromatin immunoprecipitation assays
      further demonstrate that MUC1 (1) associates with ERalpha complexes on estrogen
      responsive promoters, (2) enhances ERalpha promoter occupancy, and (3) increases
      recruitment of the p160 coactivators SRC-1 and GRIP1. In concert with these
      results, we show that MUC1 stimulates ERalpha-mediated transcription and
      contributes to E2-mediated growth and survival of breast cancer cells. These
      findings provide evidence that MUC1 stabilizes ERalpha and that this oncoprotein
      is of importance to the activation of ERalpha function.

PMID- 16427020
TI  - Economic deregulation and transport safety: a synthesis of evidence from
      evaluation studies.
AB  - This paper presents a synthesis of evidence from studies that have evaluated the
      impacts of economic deregulation on transport safety. Most of these studies refer
      to aviation or road transport. Very few studies deal with deregulation of rail
      transport. There are no studies of maritime transport, which has never been
      regulated the same way as other modes of transport. The review includes studies
      that have attempted to quantify the impacts of transport deregulation on
      transport safety. Each study contains one or more estimates of the effect on
      transport safety of deregulation. Summary estimates of effect have been derived
      from the individual estimates of effect by means of meta-analysis. Airline
      deregulation, which has only been evaluated in the United States, does not appear
      to influence the safety of air travel. Deregulation of road transport has been
      evaluated in several countries. The summary estimate of effect indicates that no
      statistically significant changes in road safety have occurred as a result of
      deregulation. Deregulation of rail transport has only been evaluated in Great
      Britain and the United States. The experience so far suggests that deregulation
      of railways is associated with improved rail safety. This association does,
      however, not necessarily imply a causal relationship.

PMID- 16427021
TI  - [Publishing a randomized trial in French language is still an exception].

PMID- 16427022
TI  - The effect of shoe sole tread groove depth on the friction coefficient with
      different tread groove widths, floors and contaminants.
AB  - Slipping and falling are common phenomena in both workplaces and our daily
      activities. The risks associated with slipping and falling are related to the
      materials of footwear/floor, contamination condition, and geometric design of the
      sole. Shoe soles of various tread design are very common. Tread pattern of the
      shoe affects friction especially under liquid-contaminated conditions.
      Verification of the effects of tread groove depth is significant in assisting
      designers in designing proper footwear for workers exposed to slippery floor
      conditions. In this study, we measured the friction coefficients using the
      Neolite footwear pads on the terrazzo, steel, and vinyl floors under three liquid
      contaminated conditions. A Brungraber Mark II slipmeter was used. The footwear
      pads had tread grooves with a width of either 3 or 9mm. The depth of the tread
      grooves ranged from 1 to 5mm. The results showed that tread groove depth affected
      the friction coefficients significantly. Higher friction values were recorded for
      footwear pads with deeper tread grooves on wet and water-detergent-contaminated
      floors. The averaged coefficient of friction (COF) gain per tread groove depth
      increase in millimeter under these two surface conditions ranged from 0.018 to
      0.108, depending on the tread groove width, floor, and contaminant.

PMID- 16427023
TI  - Loosely packed papain prosegment displays inhibitory activity.
AB  - Most protease prosegments are co-synthesized at the N-termini of cysteine
      proteases and are involved in folding assistance, inhibition, and activation of
      their mature enzymes. By using circular dichroism, UV-difference and fluorescence
      spectroscopies, we studied the thermal unfolding of papain prosegment. The
      transition seems to be two-state and reversible, with an unfolded state prone to
      aggregation. Unfolding thermodynamic parameters obtained show low values both for
      deltaH(Tm) and deltaCp(U), indicative of a loosely packed three-dimensional
      conformation for the prosegment at near-neutral pH conditions. In spite of these
      results, fluorescence experiments demonstrate that papain prosegment is able to
      recognize and inhibit its cognate protease. An acid medium induces a molten
      globule-like state without intermediates, which in turn undergoes an irreversible
      thermal unfolding. Our results suggest that papain prosegment has a high degree
      of conformational flexibility, with the ability to form not only a molten globule
      like structure in activating conditions, but also requiring an induced fit in
      order to be functional as inhibitor.

PMID- 16427024
TI  - Dihydroxyacetone and methylglyoxal as permeants of the Plasmodium
      aquaglyceroporin inhibit parasite proliferation.
AB  - The aquaglyceroporin of Plasmodium falciparum (PfAQP) is a bi-functional channel
      with permeability for water and solutes. Its functions supposedly are in osmotic
      protection of parasites and in facilitation of glycerol permeation for
      glycerolipid biosynthesis. Here, we show PfAQP permeability for the glycolysis
      related metabolites methylglyoxal, a cytotoxic byproduct, and dihydroxyacetone, a
      ketotriose. AQP3, the red cell aquaglyceroporin, also passed dihydroxacetone but
      excluded methylglyoxal. Proliferation of malaria parasites was inhibited by
      methylglyoxal with an IC50 around 200 microM. Surprisingly, also
      dihydroxyacetone, which is an energy source in human cells, was antiproliferative
      in chloroquine-sensitive and resistant strains with an IC50 around 3 mM. We
      expressed P. falciparum glyceraldehyde 3-phosphate dehydrogenase (PfGAPDH) to
      examine whether it is inhibited by either carbonyl compound. Methylglyoxal did
      not affect PfGAPDH on incubation with 2.5 mM for 20 h. Treatment with 2.5 mM
      dihydroxyacetone, however, abolished PfGAPDH activity within 6 h.
      Aquaglyceroporin permeability for glycolytic metabolites may thus be of
      physiological significance.

PMID- 16427026
TI  - Practical applications and feasibility of efflux pump inhibitors in the clinic--a
      vision for applied use.
AB  - The world of antibiotic drug discovery and development is driven by the necessity
      to overcome antibiotic resistance in common Gram-positive and Gram-negative
      pathogens. However, the lack of Gram-negative activity among both recently
      approved antibiotics and compounds in the developmental pipeline is a general
      trend despite the fact that the plethora of covered drug targets are well
      conserved across the bacterial kingdom. Such intrinsic resistance in Gram
      negative bacteria is largely attributed to the activity of multidrug resistance
      (MDR) efflux pumps. Moreover, these pumps also play a significant role in
      acquired clinical resistance. Together, these considerations make efflux pumps
      attractive targets for inhibition in that the resultant efflux pump inhibitor
      (EPI)/antibiotic combination drug should exhibit increased potency, enhanced
      spectrum of activity and reduced propensity for acquired resistance. To date, at
      least one class of broad-spectrum EPI has been extensively characterized. While
      these efforts indicated a significant potential for developing small molecule
      inhibitors against efflux pumps, they did not result in a clinically useful
      compound. Stemming from the continued clinical pressure for novel approaches to
      combat drug resistant bacterial infections, second-generation programs have been
      initiated and show early promise to significantly improve the clinical usefulness
      of currently available and future antibiotics against otherwise recalcitrant Gram
      negative infections. It is also apparent that some changes in regulatory decision
      making regarding resistance would be very helpful in order to facilitate approval
      of agents aiming to reverse resistance and prevent its further development.

PMID- 16427025
TI  - Synthetic heteroprostanoids of A- and E-types as novel non-comprehensive
      inhibitors of adenylyl cyclase in rat hepatocytes.
AB  - Treatment of rat hepatocyte plasma membranes with five novel synthetic
      heteroprostanoids of A- and E-types significantly decreased basal activity of
      adenylyl cyclase. Inhibition of forskolin-stimulated activity of the enzyme was
      seen as well. The maximal effective concentration for all substances tested was
      found at approximately 5x10(-6)-1x10(-5) M. The values of half maximal
      concentration (IC50) for all prostanoids were at the region of 0.7-1.1 microM.
      Prostanoids belonging to cyclopentenone group A (U-39, U-26) were less active
      than analogs of 11-deoxy-PGE1 (TA-227, TA-280, and TA-239). The strongest
      inhibitory effect of adenylyl cyclase activity (more than 3 times) was determined
      in the presence of prostanoid TA-227 possessing hydrophobic 15-phenyl ring and
      isoxazol group in omega-chain. The investigation of AC activity in the presence
      of different concentrations of prostanoids and varying concentrations of Mg x ATP
      has demonstrated that a non-comprehensive mechanism with particular effect takes
      place in case of AC inhibition by the heteroprostanoids.

PMID- 16427027
TI  - Resveratrol induces apoptosis of human malignant B cells by activation of caspase
      3 and p38 MAP kinase pathways.
AB  - Red wine polyphenol, trans-resveratrol (trans-3,4',5-trihydroxy stilbene), has
      potent chemopreventive effects against various tumors. In this study, we found
      for the first time that resveratrol rapidly induces S phase cell cycle arrest of
      human malignant B cells including myeloma cells in dose- and time-dependent
      manners, followed by S phase cell cycle arrest through ATM/Chk pathway.
      Resveratrol-induced apoptosis occurs in association with the activation of
      caspase-3 and the loss of mitochondrial transmembrane potentials. In addition,
      resveratrol induces the phosphorylation of p38 MAP kinase, and specific
      inhibition of p38 MAP kinase abolishes the resveratrol-induced apoptosis,
      indicating that activation of the p38 MAP kinase pathway is required for inducing
      apoptosis in malignant B cells. These results suggest that resveratrol may have
      potential as a novel therapeutic agent for the patients with B cell malignancies
      including multiple myeloma.

PMID- 16427028
TI  - Synaptic plasticity and dysconnection in schizophrenia.
AB  - Current pathophysiological theories of schizophrenia highlight the role of
      altered brain connectivity. This dysconnectivity could manifest 1) anatomically,
      through structural changes of association fibers at the cellular level, and/or 2)
      functionally, through aberrant control of synaptic plasticity at the synaptic
      level. In this article, we review the evidence for these theories, focusing on
      the modulation of synaptic plasticity. In particular, we discuss how
      dysconnectivity, observed between brain regions in schizophrenic patients, could
      result from abnormal modulation of N-methyl-D-aspartate (NMDA)-dependent
      plasticity by other neurotransmitter systems. We focus on the implication of the
      dysconnection hypothesis for functional imaging at the systems level. In
      particular, we review recent advances in measuring plasticity in the human brain
      using functional magnetic resonance imaging (fMRI) and electroencephalography
      (EEG) that can be used to address dysconnectivity in schizophrenia. Promising
      experimental paradigms include perceptual and reinforcement learning. We describe
      how theoretical and causal models of brain responses might contribute to a
      mechanistic understanding of synaptic plasticity in schizophrenia.

PMID- 16427029
TI  - A pharmacological model for psychosis based on N-methyl-D-aspartate receptor
      hypofunction: molecular, cellular, functional and behavioral abnormalities.
AB  - BACKGROUND: The psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor
      antagonists such as phencyclidine (PCP) in healthy humans and their ability to
      exacerbate psychotic symptoms in schizophrenic patients have promoted a view of
      schizophrenia as being related to altered glutamatergic neurotransmission.
      METHODS: This prompted us and others to develop animal models for psychosis based
      on a glutamatergic approach. Pharmacological induction of a state of impaired
      glutamatergic neurotransmission based on chronic, low-dose application of MK-801,
      a highly selective noncompetitive NMDA antagonist, revealed marked parallels
      between schizophrenia and our animal model. RESULTS: MK-801 altered the
      expression of NR1 splice variants and NR2 subunits of the NMDA receptor in a
      pattern partially resembling the alterations detected in schizophrenia.
      Ultrastructurally, the number of gamma-aminobutyric-acid (GABA)ergic parvalbumin
      positive interneurons was relatively decreased, a finding which again parallels
      observations in post mortem brain from schizophrenic patients. As a functional
      consequence, local inhibition of pyramidal cells which is largely mediated by
      recurrent axon collaterals, originating from GABAergic interneurons, was altered.
      Not unexpectedly, these animals showed cognitive deficits resembling findings in
      schizophrenic humans. CONCLUSIONS: These convergent lines of evidence suggest
      that our approach has a significant potential of serving as a model of the
      pathobiology of several aspects of psychosis and consequently could contribute to
      the development of new therapeutic strategies.

PMID- 16427030
TI  - Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine
      release in a memantine-like fashion and protect against behavioral sensitization.
AB  - BACKGROUND: Amphetamine administration induces stimulation-independent dopamine
      release in the nucleus accumbens (NAcc) through reverse dopamine transport, a
      critical neurochemical event involved in its psychostimulant action, and
      furthermore decreases stimulation-dependent vesicular dopamine release. These
      effects may involve possible indirect glutamatergic mechanisms. METHODS: We
      investigated the effects of nitrous oxide and xenon, which possess antagonistic
      action at the N-methyl-D-aspartate (NMDA) receptor, on brain slices ex vivo on
      amphetamine-induced changes in carrier-mediated and KCl-evoked dopamine release
      in the NAcc, and in vivo on amphetamine-induced locomotor sensitization. RESULTS:
      Like the low-affinity NMDA receptor antagonist memantine, but not the
      prototypical compound MK-801, nitrous oxide and xenon at appropriate
      concentrations blocked both the increase in carrier-mediated dopamine release and
      locomotor sensitization produced by amphetamine. CONCLUSIONS: In contrast to what
      has generally been found using prototypical NMDA receptor antagonists, these data
      regarding the effect of memantine, nitrous oxide, and xenon support the
      hypothesis that activation of certain NMDA receptors (possibly those containing
      the NR1a/NR2D subunit) in the NAcc is involved in the amphetamine-induced
      increase in carrier-mediated dopamine release and the development of behavioral
      sensitization to amphetamine. Nitrous oxide, xenon, and memantine may be of
      therapeutic interest for treating drug dependence.

PMID- 16427031
TI  - ROR alpha in genetic control of cerebellum development: 50 staggering years.
AB  - The staggerer mutation was first identified at the Jackson Laboratory in 1955. In
      the ensuing half-century, studies of staggerer mice have provided new insights
      into developmental neurobiology, gene regulatory networks, and circadian
      behavior. Recent work has expanded the role of RORalpha, the transcription factor
      mutated in staggerer, to peripheral tissues, including cholesterol and lipid
      metabolism, immune function, and bone development. This review focuses on the
      role of RORalpha in neural development and behavior revealed by the staggerer
      mutation and subsequent molecular studies.

PMID- 16427032
TI  - Systemic administration of minocycline inhibits formalin-induced inflammatory
      pain in rat.
AB  - It has been demonstrated that spinal microglial activation is involved in
      formalin-induced pain and that minocycline, an inhibitor of microglial
      activation, attenuate behavioral hypersensitivity in neuropathic pain models. We
      investigated whether minocycline could have any anti-nociceptive effect on
      inflammatory pain, after intraperitonial administration of minocycline, 1 h
      before formalin (5%, 50 microl) injection into the plantar surface of rat
      hindpaw. Minocycline (15, 30, and 45 mg/kg) significantly decreased formalin
      induced nociceptive behavior during phase II, but not during phase I. The
      enhancement in the number of c-Fos-positive cells in the L4-5 spinal dorsal horn
      (DH) and the magnitude of paw edema induced by formalin injection during phase II
      were significantly reduced by minocycline. Minocycline inhibited synaptic
      currents of substantia gelatinosa (SG) neurons in the spinal DH, whereas membrane
      electrical properties of dorsal root ganglion neurons were not affected by
      minocycline. Analysis with OX-42 antibody revealed the inhibitory effect of
      minocycline on microglial activation 3 days after formalin injection. These
      results demonstrate the anti-nociceptive effect of minocycline on formalin
      induced inflammatory pain. In addition to the well-known inhibitory action of
      minocycline on microglial activation, the anti-edematous action in peripheral
      tissue, as well as the inhibition of synaptic transmission in SG neurons, is
      likely to be associated with the anti-nociceptive effect of minocycline.

PMID- 16427034
TI  - Effects of a partial D2-like receptor agonist on striatal dopamine autoreceptor
      functioning in preweanling rats.
AB  - There is evidence that partial D2-like dopamine agonists (e.g., terguride) may
      not affect D2-like postsynaptic receptors in an adult-typical manner during the
      preweanling period. To determine whether synthesis modulating dopamine
      autoreceptors are also affected in an adult atypical manner by partial D2-like
      agonists, preweanling rats were treated either acutely or repeatedly with
      reserpine (low dopaminergic tone) or vehicle (high dopaminergic tone). The
      ability of terguride, quinpirole (a full D2-like agonist), or haloperidol (a D2
      like antagonist) to alter striatal DOPA accumulation was assessed after NSD-1015
      treatment on postnatal day (PD) 21. In a separate set of experiments, terguride's
      ability to modulate dopamine synthesis was assessed in rats treated with the
      nerve impulse flow inhibitor gamma-butyrolactone (GBL). Results showed that both
      terguride and quinpirole reduced striatal DOPA accumulation during a state of low
      dopaminergic tone (i.e., after reserpine pretreatment). During a state of high
      dopaminergic tone (i.e., after vehicle pretreatment), terguride had similar
      effects as haloperidol and increased DOPA accumulation. Terguride, like
      quinpirole, partially inhibited the GBL-induced increase in striatal DOPA
      accumulation. When considered together, these results indicate that synthesis
      modulating D2-like autoreceptors are functional during the late preweanling
      period, and they respond in an adult-typical manner to a partial D2-like agonist.

PMID- 16427033
TI  - Specialization of phonological and semantic processing in Chinese word reading.
AB  - The purpose of this study was to examine the neurocognitive network for
      processing visual word forms in native Chinese speakers using functional magnetic
      resonance imaging (fMRI). In order to compare the processing of phonological and
      semantic representations, we developed parallel rhyming and meaning association
      judgment tasks that required explicit access and manipulation of these
      representations. Subjects showed activation in left inferior/middle frontal gyri,
      bilateral medial frontal gyri, bilateral middle occipital/fusiform gyri, and
      bilateral cerebella for both the rhyming and meaning tasks. A direct comparison
      of the tasks revealed that the rhyming task showed more activation in the
      posterior dorsal region of the inferior/middle frontal gyrus (BA 9/44) and in the
      inferior parietal lobule (BA 40). The meaning task showed more activation in the
      anterior ventral region of the inferior/middle frontal gyrus (BA 47) and in the
      superior/middle temporal gyrus (BA 22,21). These findings are consistent with
      previous studies in English that suggest specialization of inferior frontal
      regions for the access and manipulation of phonological vs. semantic
      representations, but also suggest that this specialization extends to the middle
      frontal gyrus for Chinese. These findings are also consistent with the suggestion
      that the left middle temporal gyrus is involved in representing semantic
      information and the left inferior parietal lobule is involved in mapping between
      orthographic and phonological representations.

PMID- 16427035
TI  - Two-dimensional 13C-1H heteronuclear correlation NMR spectroscopic studies for
      the inclusion complex of cyclomaltoheptaose (beta-cyclodextrin) with a new
      Helicobacter pylori eradicating agent (TG44) in the amorphous state.
AB  - The interaction of a newly developed Helicobacter pylori eradicating agent (TG44,
      4-methylbenzyl-4'-[trans-4-(guanidinomethyl)cyclohexylcarbonyloxy]-biphenyl-4
      carboxlylate monohydrochloride) with cyclomaltoheptaose (beta-cyclodextrin, beta
      CyD) in the solid state was studied by high-speed frequency-switched Lee-Goldburg
      (FSLG) (13)C-(1)H heteronuclear correlation (HETCOR) NMR experiments. The
      TG44/beta-CyD solid complex in a 1:1 stoichiometry was prepared by the grinding
      method. Powder X-ray diffractometry confirmed that the complex is in an amorphous
      state. The solid-state (13)C signals of TG44 and beta-CyD were significantly
      broadened by the complexation. As the temperature increased, the (13)C signals of
      the aromatic moieties of TG44 were insignificantly influenced, whereas those of
      the cyclohexyl moiety became sharper. The T1(rho) H values of the aromatic
      moieties of TG44 were almost the same as those of the beta-CyD carbons, whereas
      those of other TG44 carbons gave much smaller values. The (13)C-(1)H HETCOR
      spectra gave the intermolecular correlation peaks between the aromatic carbons of
      TG44 and the beta-CyD protons or between the biphenyl protons of TG44 and the
      beta-CyD carbons, when measured using longer contact times (500 and 1500mus). On
      the basis of these solid NMR spectroscopic data together with aqueous NMR data,
      we assume that beta-CyD includes predominantly the biphenyl moiety of TG44 in the
      solid state. (13)C-(1)H HETCOR spectroscopy is particularly useful for the
      determination of inclusion modes of the complexes that occurring in an amorphous
      form.

PMID- 16427036
TI  - From tadpole tails to transgenic mice: metalloproteinases have brought about a
      metamorphosis in our understanding of cardiovascular disease.

PMID- 16427037
TI  - Evaluation of an algorithm of tagging SNPs selection by linkage disequilibrium.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most abundant kind of
      genetic polymorphism in the human genome. They are important in both genetic
      research and genetic testing in a clinical setting, such as in the area of
      pharmacogenetics. In order to improve efficiency, tagging SNPs (tagSNPs) are
      selected in genes of interest to represent other co-related SNPs in linkage
      disequilibrium (LD) with the tagSNPs. Various algorithms have been proposed to
      identify a subset of single nucleotide polymorphisms as tagSNPs. Most algorithms
      of tagSNPs selection are haplotype-based, in which the spatial relationship
      between SNPs is considered. Currently, a more efficient cluster-based algorithm
      is proposed which clusters SNPs solely by a LD parameter, such as r(2). Here, we
      evaluated the sample distribution of r(2) and its effect on the cluster-based
      tagSNPs selection. DESIGN AND METHODS: The genotype data of 198 individual within
      a 500-kb region on 5q31 was used to evaluate the sample distribution of r(2) and
      its effect on the cluster-based tagSNPs selection. RESULTS: It was found that the
      degree of variation of LD depends on the LD structure of genes. CONCLUSION: As a
      cluster-based tagSNPs selection algorithm does not take into account the spatial
      position of SNPs, a more stringent r(2) threshold is required to achieve more
      reliable tagSNPs selection.

PMID- 16427038
TI  - Molecular characterization of the developmental gene in eyes: through data-mining
      on integrated transcriptome databases.
AB  - OBJECTIVES: Our aim was to utilize publicly available and proprietary sources to
      discover candidate genes important for ocular development. DESIGN AND METHODS:
      The collated information on our 5092 non-redundant clusters was grouped and
      functional annotation was conducted using gene ontology (FatiGO) for categorizing
      them with respect to molecular function. The web-based viewer technological
      platform (H-InvDB) was employed for transcription analyses of in-house high
      quality fetal eye Expressed Sequence Tags (ESTs). Eye-specific ESTs were also
      analyzed across species by using EMBEST. RESULTS: According to adult eye cDNA
      libraries, nucleic acid binding and cell structure/cytoskeletal protein genes
      were the most abundant among the ESTs of fetal eyes. Using cDNA assembly in H
      InvDB, 20 (80%) of the 25 most commonly expressed genes in the human eye are also
      expressed in extraocular tissues. The crystalline gamma S gene is highly
      expressed in the eye, but not in other tissues. We used EMBEST to compare human
      fetal eye and octopus eye ESTs and the expression similarity was low (1.6%). This
      indicated that our fetal eye library contains genes necessary for the
      developmental process and biological function of the eye, which may not be
      expressed in the fully developed octopus eyes. The human fetal eye cDNA library
      also contained highly abundant eye tissue genes, including alphaA-crystallin,
      eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), bestrophin (VMD2),
      cystatin C, and transforming growth factor, beta-induced (BIGH3). CONCLUSIONS:
      Our annotated EST set provides a valuable resource for gene discovery and
      functional genomic analysis. This display will help to appreciate the strengths
      and weaknesses of the different technological platforms, so that in future
      studies the maximum amount of beneficial information can be derived from the
      appropriate use of each method.

PMID- 16427040
TI  - Distinct roles for retinoic acid receptors alpha and beta in early lung
      morphogenesis.
AB  - Retinoic acid (RA) signaling is required for normal development of multiple
      organs. However, little is known about how RA influences the initial stages of
      lung development. Here, we used a combination of genetic, pharmacological and
      explant culture approaches to address this issue, and to investigate how
      signaling by different RA receptors (RAR) mediates the RA effects. We analyzed
      initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null
      mice, a model in which RA signaling is absent from the foregut from its earliest
      developmental stages. We provide evidence that RA is dispensable for
      specification of lung cell fate in the endoderm. By using synthetic retinoids to
      selectively activate RAR alpha or beta signaling in this model, we demonstrate
      novel and unique functions of these receptors in the early lung. We show that
      activation of RAR beta, but not alpha, induces expression of the fibroblast
      growth factor Fgf10 and bud morphogenesis in the lung field. Similar analysis of
      wild type foregut shows that endogenous RAR alpha activity is required to
      maintain overall RA signaling, and to refine the RAR beta effects in the lung
      field. Our data support the idea that balanced activation of RAR alpha and beta
      is critical for proper lung bud initiation and endodermal differentiation.

PMID- 16427039
TI  - Decreased expression of pro-apoptotic Bcl-2 family members during retinal
      development and differential sensitivity to cell death.
AB  - Apoptosis plays a crucial role in the sculpture of the mammalian retina during
      development. However, once the retina is fully differentiated, the emphasis must
      shift towards survival and mechanisms have to be put in place to prevent
      inappropriate cell death. In this study, we identify a potential control point at
      the level of mitochondrial permeability. We show that pro-apoptotic Bcl-2 family
      members known to be involved in the regulation of permeability transition and
      physiological cell death in the retina are down regulated during postnatal
      retinal development. In addition, we demonstrate an age-dependent susceptibility
      to retinal cell death induced by various stimuli known to target mitochondrion.
      These results potentially explain why retinal cells employ different death
      pathways depending on their stage of development. In contrast to developmental
      apoptosis, pathological retinal cell death in several animal models has been
      reported to occur independently of caspase activation. Here, we show that not
      only is cytochrome c release precluded from degenerating retinas but other pro
      death molecules such as Omi/HtrA2 and AIF also remain in the mitochondrion. Our
      results indicate that transcriptional regulation of 'death genes' such as pro
      apoptotic Bcl-2 family members during retinal development affords protection in
      adult post-mitotic neurons by preventing execution of the archetypal
      mitochondrial death pathway.

PMID- 16427042
TI  - Systemic evaluation of total Stat3 and Stat3 tyrosine phosphorylation in normal
      human tissues.
AB  - Stat3 plays important roles in many biological phenomena including cell survival,
      growth, proliferation, differentiation and cancer malignancies. As Stat3 emerges
      as a new therapeutic target for treatment of cancers in which the Stat3 is
      constitutively activated, the overall evaluation of basal expression of Stat3 and
      phosphorylated Stat3 at tyrosine residue 705 in human tissues would be very
      important and informative. We took a pilot study to examine the expression
      patterns of total Stat3 and phosphorylated Stat3 protein (p-Stat3) using
      immunohistochemistry in 47 different adult normal human tissues of 10 organ
      systems. Immunohistochemistry showed that total Stat3 protein was almost
      universally detected in all tissues except peripheral nerve. Interestingly,
      majorities of tissues showed to have moderate to high expression levels of total
      Stat3 protein. Several heart tissues displayed a unique perinuclear
      immunostaining for both Stat3 and p-Stat3, most likely in Golgi complexes. Based
      on the cell types, the p-Stat3 was also expressed in glandular, secretory,
      mucosal epithelial, circulatory endothelial, lymphoid, proliferative, and
      reabsorption-active cells.

PMID- 16427041
TI  - Effects of tramadol and O-demethyl-tramadol on human 5-HT reuptake carriers and
      human 5-HT3A receptors: a possible mechanism for tramadol-induced early emesis.
AB  - ([3H]5-HT)-uptake and patch-clamp techniques were used to study the actions of
      (+) and (-) tramadol and the active metabolites of tramadol, (+) and (-) O
      demethyl-tramadol on the human serotonin (5-HT) transporter and the human 5-HT3A
      receptor, stably expressed in HEK-293 cells. The (+) and (-) enantiomers of
      tramadol suppressed the human 5-HT transporter concentration-dependently
      (IC50=1.0 and 0.8 microM, respectively), resulting in 97% and 87% transport
      inhibition at their respective initial plasma concentrations (9.5 microM). The
      (+) and (-) enantiomers of the active tramadol metabolite were less potent than
      tramadol in inhibiting the human 5-HT transporter (IC50=15 and 44 microM,
      respectively), resulting in 19.2% and 4.8% transport inhibition at their highest
      plasma concentrations (2.5 microM). In contrast to their potent suppression of
      the 5-HT transporter, both, (+) and (-) tramadol inhibited 5-HT (30 microM)
      induced currents only at substantially higher concentrations (IC50=199 and 251
      microM, respectively), resulting in only 6% and 4% inhibition at the initial
      maximum plasma concentration. A similar low potent inhibition of human 5-HT(3A)
      receptors was found for (+) and (-) O-demethyl-tramadol (IC50=158 and 63 microM,
      respectively). In conclusion, at clinical plasma concentrations tramadol potently
      suppresses the human 5-HT transporter, whereas it has only a slight effect on the
      human 5-HT3A receptor. The results are compatible with a possible mechanism for
      tramadol-induced early emesis involving the serotonergic system.

PMID- 16427043
TI  - Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its
      nuclear accumulation is linked to poor prognosis for human gastric cancer.
AB  - Chromosomal passenger proteins including Aurora B, Survivin, and Borealin/Dasra
      B, also called CDCA8/FLJ10468, are known to play crucial roles during mitosis and
      cell division. Inappropriate chromosomal segregation and cell division may cause
      auneuploidy leading to cancer. However, it is still unclear how the expression of
      chromosomal passenger proteins may be linked to cancer. In this study, we
      demonstrated that Borealin is a cell cycle-regulated gene and is upregulated at
      G2-M phases of the cell cycle. We showed that Borealin interacts with Survivin
      but not with Aurora B. The interaction domain of Survivin in Borealin was mapped
      to the N-terminal 92 amino-acid residues of Borealin. To examine the linkage
      between expression of Borealin and cancer, we performed immunohistochemistry
      analysis using anti-Borealin specific antibody on the paraffin-embedded gastric
      cancer tissues. Our results showed that Borealin expression is significantly
      correlated with Survivin (P = 0.003) and Ki67 (P = 0.007) in gastric cancer.
      Interestingly, an increased nuclear Borealin level reveals borderline association
      with a poor survival rate (P = 0.047). Taken together, our results demonstrated
      that Borealin is a cell cycle-regulated chromosomal passenger protein and its
      aberrant expression is linked to a poor prognosis for gastric cancer.

PMID- 16427044
TI  - Interferon-gamma-induced dephosphorylation of STAT3 and apoptosis are dependent
      on the mTOR pathway.
AB  - Interferon-gamma (IFN-gamma) exhibits diverse biological activities, including
      control of cell growth and tumor suppression. Here, we report that the treatment
      of M12 cells, a human metastatic prostate cancer cell line, with IFN-gamma,
      resulted in marked inhibition of cell proliferation and induced apoptosis. These
      effects were not seen with either IFN-alpha or IFN-beta. M12 cells, like many
      other human cancer cells, contain constitutively activated signal transducer and
      activator of transcription 3 (STAT3). The basal levels of both Akt and ERK1/2
      phosphorylation are also markedly elevated in M12 cells. Strikingly, IFN-gamma
      induced apoptosis and growth inhibition of M12 cells were associated with
      persistent suppression of the constitutive tyrosine-phosphorylated STAT3 (pY
      STAT3). The IFN-gamma-induced dephosphorylation of pY-STAT3, however, was
      inhibited when the mTOR pathway was specifically blocked by rapamycin. Inhibition
      of PI-3K with low-dose LY294002, or MAPK with PD98059 also suppressed the
      mTOR/p70 S6k pathway, and correlated with the blockage of IFN-gamma-induced
      dephosphorylation of pY-STAT3. Simultaneously, treatment with LY294002, PD98059,
      or rapamycin abolished IFN-gamma-induced apoptosis in M12 cells. The inhibition
      of the mTOR pathway, however, did not affect IFN-gamma-induced activation of
      STAT1 pathway, and suppression of STAT1 expression by siRNA had no effect on IFN
      gamma-induced dephosphorylation of pY-STAT3. Taken together, these results
      demonstrate that an intact mTOR pathway is critical for IFN-gamma-induced
      suppression of pY-STAT3 and apoptosis. Our study thus provides novel insights
      into the contributions of signaling pathways other than the classical JAK/STAT1
      pathway in the anti-proliferative, proapoptotic actions of IFN-gamma.

PMID- 16427045
TI  - Thrombin in ischemic neuronal death.
AB  - Thrombin plays a role in cerebral ischemia as rats subjected to focal cerebral
      ischemia were protected by the intracerebral injection of hirudin, a selective
      thrombin inhibitor. To separate the roles of thrombin in cell death and in
      coagulation, we have used an in vitro approach to test the effect of hirudin and
      of protease nexin-1 (PN-1), a cerebral thrombin inhibitor, on neuronal ischemia.
      Rat organotypic hippocampal slice cultures were subjected to oxygen (5%) and
      glucose (1 mmol/L) deprivation (OGD) during 30 min. Hirudin or PN-1 administered
      after OGD significantly prevented neuronal death in the CA1 region. After 24 h,
      there was a marked increase in thrombin immunoreactivity on Western blots.
      Thrombin therefore contributes to ischemic damage in neural tissue in vitro.

PMID- 16427046
TI  - Cell cycle and cell death regulation of neural progenitor cells in the 5
      azacytidine (5AzC)-treated developing fetal brain.
AB  - In the developing brain, neural progenitor cells are susceptible to many
      extrinsic stresses, including DNA damage. We treated pregnant rats with 5
      azacytidine (5AzC), a DNA demethylating and damaging agent, to investigate the
      cellular responses of the fetal brain, focusing on the regulation of
      proliferation and cell death. 5AzC first induced the accumulation of cells in
      abnormal mitosis, G2-phase accumulation, and then apoptosis of the neural
      progenitor cells. Most of the apoptotic cells were in G1 phase. Cell cycle
      transition studies suggested that G2/M progression was blocked, after which the
      cells moved to G1 phase or underwent apoptosis. p53, a key factor for response to
      DNA damage, and some of its target genes showed increased expression in Western
      blot and DNA microarray analyses. In 5AzC-treated fetal brains of p53-deficient
      mice, apoptosis did not occur, although G2/M accumulation was induced. These
      results suggest that, in the developing brain, apoptosis is p53-dependent but
      that another mechanism governs the G2/M checkpoint. The G2/M regulator, Cdc2, was
      activated by dephosphorylation through G2/M accumulation, suggesting accelerated
      entry into mitosis leading to accumulation of cells showing abnormal mitosis.
      Furthermore, some cells may have died due to mitotic catastrophe. Throughout
      brain development, various cell cycle and cell death regulation mechanisms
      provide neural progenitor cells with options for defense from DNA damage.

PMID- 16427047
TI  - Time course and outcome of recovery from stroke: relevance to stem cell
      treatment.
AB  - Stroke is the third leading cause of death in the United States after heart
      disease and cancer; it has an incidence of approximately 750,000 cases per year,
      and it is a leading cause of disability in adults. The factors predicting a poor
      outcome from stroke include severe initial neurological dysfunction,
      hypertension, cardiac arrhythmias, myocardial infarction, hypercholesterolemia,
      and diabetes mellitus. The armamentarium available for improvement of
      neurological function after stroke is currently limited to placement in
      specialized stroke units, optimal therapy for medical complications, and intense
      physical, occupational and speech rehabilitation. Despite many trials, no
      pharmacological intervention has been shown convincingly to improve neurological
      outcome. This review was undertaken to determine the appropriate time for new
      approaches to the therapy of stroke such as the infusion of stem cells into the
      central nervous system. The literature shows in large case series that functional
      recovery from stroke reaches a maximum level by 3-6 months after onset, and no
      further recovery occurs beyond this time. Nevertheless, about 80% of these
      patients reach their maximum function for activities of daily living within 6
      weeks from onset. Initiation of a clinical trial of stem cell therapy would
      require demonstration of optimal clinical improvement by neurological
      evaluations, with no change over at least 4 weeks of observation. Accordingly, in
      subjects with first-ever ischemic stroke who remained neurologically unchanged
      from the second until the third month after the acute event, implementation of
      stem cell therapy would be appropriate at approximately 3 months after the
      stroke.

PMID- 16427048
TI  - Intranuclear disposition of exogenous DNA in vivo: silencing, methylation and
      fragmentation.
AB  - The intranuclear disposition of exogenous DNA is highly important for the
      therapeutic effects of the administrated DNA. Naked luciferase-plasmid DNA was
      delivered into mouse liver by a hydrodynamics-based injection, and the amounts of
      intranuclear plasmid DNA, luciferase, and its mRNA were quantitated at various
      time points. Methylation of the promoter of the luciferase gene was also
      analyzed. Expression efficiency from one copy of the exogenous DNA dramatically
      decreased over time, and the DNA was methylated and degraded into fragments.
      Unexpectedly, methylation of the intact plasmid DNA was low and did not increase
      over time. Rather, the fragmented DNA was methylated more frequently than the
      intact plasmid. These results suggest that the CpG methylation and the
      degradation of exogenous DNA, and its 'silencing', occurred in parallel in the
      nucleus.

PMID- 16427049
TI  - Expression of APOBEC2 is transcriptionally regulated by NF-kappaB in human
      hepatocytes.
AB  - Apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) is a member of
      the nucleic-acid-editing enzymes. However, the physiological function of APOBEC2
      remains unclear. We demonstrate that APOBEC2 expression is strongly enhanced in
      response to both tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta.
      Inhibition of NF-kappaB activation invariably blocks TNF-alpha-induced APOBEC2
      expression. The promoter region of APOBEC2 contains functional NF-kappaB response
      elements in the 5' untranslated region of the gene at -625/-616. These results
      show that APOBEC2 expression is regulated by pro-inflammatory cytokines via NF
      kappaB activation and suggest a possible role of APOBEC2 in the pathophysiology
      of hepatic inflammation.

PMID- 16427050
TI  - Activation of p53 as a causal step for atherosclerosis induced by polycyclic
      aromatic hydrocarbons.
AB  - This study was performed to prove our hypothesis that the metabolite(s) of
      polycyclic aromatic hydrocarbons (PAHs) caused the activation or phosphorylation
      of p53 via DNA damage to suppress the liver X receptor (LXR)-mediated signal
      transductions as a probably more direct mechanism. We found that LXR-mediated
      trans-activation was inhibited by 3-methylchoranthrene (MC) and doxorubicin (Dox)
      in HepG2 cells carrying wild-type p53, but not in Hep3B cells possessing mutant
      p53. The exogenous expression of wild-type p53 suppressed the LXR-mediated trans
      activation in Hep3B cells. The expression of mRNA for ATP binding cassette A1 was
      suppressed by MC and Dox in HepG2 cells. The protein expression of retinoid X
      receptor (RXR), a partner of LXR to form a heterodimer, was suppressed by MC and
      Dox in HepG2 cells.

PMID- 16427051
TI  - Identification of sea lamprey GTHbeta-like cDNA and its evolutionary
      implications.
AB  - We have identified the first and perhaps only gonadotropin beta-like protein by
      cDNA cloning in sea lamprey, a member of the oldest lineage of vertebrates, the
      agnathans. Two pituitary gonadotropins (GTHs: follicle-stimulating hormone (FSH)
      and luteinizing hormone (LH)) have been identified in representative species of
      all classes of vertebrates except the agnathans. The present study was undertaken
      to identify GTH in sea lamprey, Petromyzon marinus, to gain a further
      understanding of the origin and evolution of reproductive pituitary hormones and
      their respective genes in vertebrates. Sea lamprey preGTHbeta-like cDNA was
      cloned from a plasmid cDNA library using an expressed sequence tag analysis. The
      preGTHbeta-like cDNA encoded 150 amino acids, in which the GTHbeta-like protein
      consisted of 134 amino acid residues. Sea lamprey GTHbeta-like protein contained
      12 Cys residues and two N-glycosylation sites at homologous positions to those of
      FSHbeta and LHbeta. The region of the molecule that has been proposed to control
      receptor binding specificity (i.e., the region between the 10th and 12th Cys
      residues) suggests that the proposed heterodimer would be more like a FSH than a
      LH. Sea lamprey GTHbeta-like protein-producing cells were identified
      immunocytochemically in the ventral part of the proximal pars distalis of
      pituitary using antiserum prepared against a synthetic peptide of preGTHbeta-like
      protein (52-68). Intraperitoneal administration of sea lamprey GnRH-I and -III at
      100 microg/g body weight (twice at a 24h interval) increased expression of
      GTHbeta-like protein in the pituitary of adult female sea lamprey during the
      final maturational period. Thus, these results are the first to demonstrate the
      presence of a single GTH-like system in lampreys. Because the sea lamprey GTHbeta
      like protein is a clear out-group compared to those of the LH and FSH family
      based on phylogenic analysis, we propose that an ancestral glycoprotein hormone
      gave rise to only one GTH in lampreys and to the glycoprotein hormone family that
      gave rise to LH, FSH, and TSH during the early evolution of gnathostomes.

PMID- 16427052
TI  - Expression of hypothalamic GnRH-I mRNA in the female turkey at different
      reproductive states and following photostimulation.
AB  - In birds, changes in hypothalamic gonadotropin-releasing hormone-I (GnRH-I)
      content and release are correlated with reproductive stages. This study examined
      the distribution and expression level of GnRH-I mRNA in anatomically discrete
      hypothalamic nuclei throughout the turkey reproductive cycle and following
      photostimulation. GnRH-I mRNA expression was determined using in situ
      hybridization in non-photostimulated (NPS), egg-laying (LAY), incubating (INC)
      and photorefractory (REF) hens. Overall, GnRH-I mRNA expression was greatest in
      the nucleus commissurae pallii (nCPa) and around the organum vasculosum lamina
      terminalis (OVLT), with less expression observed in the nucleus septalis
      lateralis (SL), cortico-habenula cortico-septum area, and within the nucleus
      preopticus medialis. GnRH-I mRNA expression was significantly increased in nCPa,
      OVLT, and SL after NPS hens (6L:18D) were exposed to a 30 or 90 min pulse of
      light beginning 14 h after first light (dawn). GnRH-I mRNA abundance within nCPa,
      OVLT and SL was greater in LAY than in NPS and INC hens, while mRNA expression
      was least in REF hens. These results indicate that GnRH-I mRNA expression in
      birds is sensitive to light stimulation during the photosensitive period and can
      be used to more precisely characterize their different reproductive stages.

PMID- 16427053
TI  - Ashkenazi levites' "Y modal haplotype" (LMH)-- an artificially created
      phenomenon?
AB  - The article on the Y chromosomes of Ashkenazi Levites (Behar et al., 2003. Am. J.
      Hum. Genet. 73, 768-779) is the fourth in a series on the Y chromosomes of the
      three Jewish male castes: Cohanim (priests), Levites (priests' helpers) and
      Israelites (lay people). It became apparent that there is a problem with omission
      of samples when the second article "Origins of Old Testament priests" (Thomas et
      al., 1998. Nature 394, 138-140) was published. In the fourth article a remarkable
      55% of the Ashkenazi Levite samples from the earlier 1998 study are not included.
      This causes the "Levite modal haplotype" to double its frequency from 21% of the
      Ashkenazi Levite sample in 1998 to 42% of the Ashkenazi Levite sample in 2003.
      The authors offer three main explanations: (1) The studies are independent using
      different sample sets.(2) Typing errors and poor quality exclude samples from
      future studies.(3) Correction of typing errors means that some samples are
      classified under different haplotypes. The explanations offered to the problem of
      omitting samples from subsequent studies after their haplotypes or partial
      haplotypes are known, are not convincing. Consequently their sample sets cannot
      be considered random and non-biased. At the least, these laboratories have bad
      practices of sample handling and many typing errors, which are enough to
      invalidate their studies.

PMID- 16427054
TI  - Long term outcomes 12 years after major trauma.
AB  - AIM: To provide long term population-based follow up on major trauma patients 12
      years after injury. METHODS: This cohort study was based on a stratified random
      sample of patients with an injury severity score greater than 15 who reached
      hospital alive in 1990-1991. The patient details were used to trace them and to
      assess the patients' recovery, using endpoints of current employment status and
      any current physical or mental health problems. A Glasgow outcome score was
      allocated on the basis of these replies. RESULTS: Of 239 patients included in the
      original tranche, (23.2/100,000), 165 (16/100,000) survived to hospital
      discharge. 138 (86%) were traced, and 4 patients had left the country. Patients
      mean age was 34 (range 2-93). The male to female ratio was approximately 3:1.
      Twenty-one patients had died since discharge, due to unrelated illnesses. One
      hundred and five (76%) were living independently (GOS 4 and 5). Eleven patients
      (8%) were severely disabled, requiring assistance with activities of daily
      living. One patient remains in a persistent vegetative state. Return to work
      rates for those working at time of injury (and who remain of employable age) was
      90%. The unemployment rate in the study population who are of working age was 34%
      (pre-injury rate 13%). The unemployment rate for those injured before their 17th
      birthday is currently 52%. CONCLUSION: We now have 12 year population based
      outcome data for major trauma. Despite major injury, 90% of long term survivors
      are living independently, with 90% returning to work. There is a trend towards
      higher unemployment when injured in childhood.

PMID- 16427056
TI  - Postpartum hemorrhage in resource-poor settings.
AB  - Despite the strong interest of international health agencies, worldwide maternal
      mortality has not declined substantially over the past 10 years. Postpartum
      hemorrhage (PPH) is the most common cause of maternal death across the world,
      responsible for more than 25% of deaths annually. Although effective tools for
      prevention and treatment of PPH are available, most are not feasible or practical
      for use in the developing world where many births still occur at home with
      untrained birth attendants. Application of many available clinical solutions in
      rural areas would necessitate substantial changes in government infrastructure
      and in local culture and customs surrounding pregnancy and childbirth. Before
      treatment can be administered, prompt and accurate diagnosis must be made, which
      requires training and appropriate blood measurement tools. After diagnosis,
      appropriate interventions that can be applied in remote settings are needed. Many
      uterotonics known to be effective in reducing PPH in tertiary care settings may
      not be useful in community settings because they require refrigeration and/or
      skilled administration. Moreover, rapid transfer to a higher level of care must
      be available, a challenge in many settings because of distance and lack of
      transportation. In light of these barriers, low-technological replacements for
      treatments commonly applied in the developed-world must be utilized. Community
      education, improvements to emergency care systems, training for birth attendants,
      misoprostol, and Uniject have shown promise as potential solutions. In the short
      term, it is expedient to capitalize on practical opportunities that utilize the
      existing strengths and resources in each community or region in order to
      implement appropriate solutions to save the lives of women during childbirth.

PMID- 16427057
TI  - The impact of nurse-directed protocolised-weaning from mechanical ventilation on
      nursing practice: a quasi-experimental study.
AB  - BACKGROUND: Internationally, nurse-directed protocolised-weaning has been
      evaluated by measuring its impact on patient outcomes. The impact on nurses'
      views and perceptions has been largely ignored. AIM: To determine the change in
      intensive care nurses' perceptions, satisfaction, knowledge and attitudes
      following the introduction of nurse-directed weaning. Additionally, views were
      obtained on how useful protocolised-weaning was to practice. METHODS: The sample
      comprised nurses working in general intensive care units in three university
      affiliated hospitals. Nurse-directed protocolised-weaning was implemented in one
      unit (intervention group); two ICUs continued with usual doctor-led practice
      (control group). Nurses' perceptions, satisfaction, knowledge and attitudes were
      measured by self-completed questionnaires before (Phase I) and after the
      implementation of nurse-directed weaning (Phase II) in all units. RESULTS:
      Response rates were 79% (n=140) for Phase 1 and 62% (n=132) for Phase II.
      Regression-based analyses showed that changes from Phase I to Phase II were not
      significantly different between the intervention and control groups. Sixty-nine
      nurses responded to both Phase I and II questionnaires. In the intervention
      group, these nurses scored their mean perceived level of knowledge higher in
      Phase II (6.39 vs 7.17, p=0.01). In the control group, role perception (4.41 vs
      4.22, p=0.01) was lower and, perceived knowledge (6.03 vs 6.63, p=0.04),
      awareness of weaning plans (6.09 vs 7.06, p=0.01) and satisfaction with
      communication (5.28 vs 6.19, p=0.01) were higher in Phase II. The intervention
      group found protocolised weaning useful in their practice (75%): this was scored
      significantly higher by junior and senior nurses than middle grade nurses
      (p=0.02). CONCLUSION: We conclude that nurse-directed protocolised-weaning had no
      effect on nurses' views and perceptions due to the high level of satisfaction
      which encouraged nurses' participation in weaning throughout. Control group
      changes are attributed to a 'reactive effect' from being study participants.
      Weaning protocols provide a uniform method of weaning practice and are
      particularly beneficial in providing safe guidance for junior staff.

PMID- 16427058
TI  - Biomechanics of vertebral level, geometry, and transcortical tumors in the
      metastatic spine.
AB  - Metastatic involvement can disrupt the mechanical integrity of the spine,
      rendering vertebrae susceptible to burst fracture and neurologic damage. Fracture
      risk assessment for patients with spinal metastases is important in considering
      prophylactic treatment options. Stability of thoracic vertebrae affected by
      metastatic disease has been shown to be dependent on tumor size and bone density,
      but additional structural and geometric factors may also play a role in fracture
      risk assessment. The objective of this study was to use parametric finite element
      modeling to determine the effects of vertebral level, geometry, and metastatic
      compromise to the cortical shell on the risk of burst fracture in the thoracic
      spine. Analysis of vertebral level and geometry was assessed by investigation of
      seven scenarios ranging in geometry from T2-T4 to T10-T12. The effects of
      cortical shell compromised were assessed by comparison of four transcortical
      scenarios to a fully contained central vertebral body tumor scenario. Results
      demonstrated that upper thoracic vertebrae are at greater risk of burst fracture
      and that kyphotic motion segments are at decreased risk of burst fracture.
      Vertebrae with transcortical lesions are up to 30% less likely to lead to burst
      fracture initiation. The findings of this study are important for improving the
      understanding of burst fracture mechanics in metastatically involved vertebrae
      and guiding future modeling efforts.

PMID- 16427059
TI  - Coordinate systems for the carpal bones of the wrist.
AB  - The eight small and complexly shaped carpal bones of the wrist articulate in six
      degrees of freedom with each other and to some extent with the radius and the
      metacarpals. With the increasing number and sophistication of studies of the
      carpus, a standardized definition for a coordinate system for each the carpal
      bones would aid in the reporting and comparison of findings. This paper presents
      a method for defining and constructing a coordinate system specific to each of
      the eight carpal bones based upon the inertial properties of the bone, derived
      from surface models constructed from three-dimensional (3-D) medical image
      volumes. Surface models from both wrists of 5 male and 5 female subjects were
      generated from CT image volumes in two neutral wrist positions (functional and
      clinical). An automated algorithm found the principal inertial axes and oriented
      them according to preset conditions in 85% of the bones, the remaining bones were
      corrected manually. Six of the eight carpal bones were significantly more
      extended in the functional neutral position than in the clinical neutral
      position. Gender had no significant effect on carpal bone posture in either wrist
      position. Correlations between the 3-D carpal posture and the commonly used 2-D
      clinical radiographic carpal angles are established. 3-D coordinate systems
      defined by the anatomy of the carpal bone, such as the ones presented here, are
      necessary to completely describe 3-D changes in the posture of the carpal bones.

PMID- 16427061
TI  - Use of multiple headspace solid-phase microextraction and pervaporation for the
      determination of off-flavours in wine.
AB  - The occurrence of off-flavours in wines and especially the so-called "cork taint
      defect" represents one of the most serious problem in wine industry in which
      2,4,6-trichloroanisole has been blamed as the main responsible. The development
      of analytical methods for haloanisoles determination in wine/cork represent a
      challenge, mainly due to food matrix complexity and low taste and odour (T&O)
      threshold levels which are generally beyond the sensitivity of the analytical
      systems. In this work, a method based on the combined use of the recently
      developed multiple headspace solid-phase microextraction (MHS-SPME) and gas
      chromatography-ion-trap mass spectrometry has been optimised for the
      determination of haloanisoles in wines. This powerful analytical methodology is
      compared with several analytical approaches based on pervaporation, an innovative
      membrane-based technique similar to dynamic headspace. Analytical features of the
      methods assayed reveal their suitability for the appraisal of haloanisoles in
      this matrix in which threshold odor concentrations are in the range 4-40 ng l(
      1). The analytical approaches have been applied to the analysis of haloanisoles
      in different Spanish white and red wines, in which spiking experiments showed
      good recoveries for the methodologies assayed.

PMID- 16427062
TI  - Hollow fiber-mediated liquid-phase microextraction of chemical warfare agents
      from water.
AB  - Unambiguous detection and identification of chemical warfare agents (CWAs) and
      related compounds are of paramount importance from verification point of view of
      Chemical Weapons Convention (CWC). It requires development of fast, reliable,
      simple and reproducible sample preparation of CWAs from water which is likely to
      be contaminated during deliberate or inadvertent spread of CWAs. This work
      describes development of hollow fiber liquid-phase microextraction (HF-LPME)
      method for efficient extraction of CWAs (such as sarin, sulfur mustard and their
      analogues) from water followed by gas chromatography-mass spectrometric analysis.
      Extraction parameters, such as organic solvent, agitation, extraction time, and
      salt concentration were optimized. Best recoveries of target analytes were
      achieved using 1 microL trichloroethylene as extracting solvent, 1000 rpm
      stirring rate, 15 min extraction time, and 30% NaCl. Excellent precision was
      observed with less than 7.6% RSD. The limit of detection by HF-LPME was achieved
      up to 0.1 microg/L at 30% salt concentration.

PMID- 16427060
TI  - Role of endplates in contributing to compression behaviors of motion segments and
      intervertebral discs.
AB  - The purpose of this study was to gain an improved understanding of the mechanical
      behavior of the intervertebral disc in the presence and absence of the vertebral
      endplates. Mechanical behaviors of rat caudal motion segments, vertebrae and
      isolated disc explants under two different permeability conditions were
      investigated and viscoelastic behaviors were evaluated using a stretched
      exponential function to describe creep and recovery behaviors. The results
      demonstrated that both vertebrae and discs underwent significant deformations in
      the motion segment even under relatively low-loading conditions. Secondly,
      disruption of the collagenous network had minimal impact on equilibrium
      deformations of disc explants as compared to disc deformations occurring in the
      motion segments provided that vertebral deformations were accounted for; however,
      differences in endplate permeability conditions had a significant effect on
      viscoelastic behaviors. Creep occurred more quickly than recovery for motion
      segment and explant specimens. In addition, disc explants and motion segments
      both exhibited non-recoverable deformations under axial compression under low-
      and high-loading conditions. Results have important implications for interpreting
      the role of vertebral endplates in contributing to disc mechanical behaviors and
      direct application to mechanobiology studies involving external loading to rodent
      tail intervertebral discs.

PMID- 16427063
TI  - Chromatographic refolding of recombinant human interferon gamma by an immobilized
      sht GroEL191-345 column.
AB  - Minichaperone sht GroEL191-345 was covalently coupled to NHS-activated Sepharose
      Fast Flow gel. Refolding of recombinant human interferon gamma (rhIFN-gamma) was
      carried out on a chromatographic column packed with immobilized minichaperone.
      The effects of salt concentration, urea concentration gradient, elution flow rate
      and protein loading on the refolding efficiency were investigated. The results
      indicated that immobilized sht GroEL191-345 chromatography was an effective
      protocol for the refolding of rhIFN-gamma. When loading 100 microl denatured
      rhIFN-gamma (17.8 mg/ml), the protein mass recovery and total activity obtained
      in this optimal process reached 74.25% and 6.74 x 10(6)IU/ml, respectively with
      the immobilized minichaperone column which was reused for 10 times with 25%
      decrease of renaturation capacity.

PMID- 16427064
TI  - Analysis on heat stress-induced hyperphosphorylation of stathmin at serine 37 in
      Jurkat cells by means of two-dimensional gel electrophoresis and tandem mass
      spectrometry.
AB  - Two-dimensional gel electrophoresis (2-DE) and tandem mass spectrometry were
      successfully used for determination of a phosphorylation site of stathmin induced
      by heat stress to Jurkat cells of a human T lymphoblastic cell line. The cells
      were incubated for 30 min at 41 degrees C up to 45 degrees C in a serum free 4-(2
      hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffered culture medium.
      The intracellular soluble proteins were separated by 2-DE, and some of the
      proteins increased their abundance by heat stress. Those proteins were identified
      to be calmodulin, protein kinase C substrate, thymosin beta-4 and F-actin capping
      protein beta-subunit by peptide mass fingerprinting (PMF) with matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). On
      the contrary, protein phosphatase 2C gamma-isoform, nucleophosmin,
      translationally controlled tumor protein, Rho GDP-dissociation inhibitor-1,
      eukaryotic translation initiation factors 5A and 3A subunit 2, ubiquitin-like
      protein SMT 3B and chloride intracellular channel protein-1 were decreased their
      abundance. A protein spot of M(r) 18,000 and pI 5.9 was markedly increased at
      temperatures higher than 43 degrees C at which the cells were led to apoptosis.
      The spot was identified to be stathmin of a signal relay protein which has a
      function of sequestering microtubule. MALDI-quadrupole ion trap (QIT)-TOF-MS/MS
      and immunoblotting with a monoclonal antibody specific for a phosphorylation site
      of stathmin showed that the spot was a phosphorylated stathmin at serine 37 (Ser
      37). The phosphorylation was suppressed by treatment of cells with olomoucine of
      an inhibitor specific for cyclin dependent kinase (Cdk-1). These results strongly
      suggest that heat stress activates Cdk-1 which phosphorylates Ser 37 on the
      stathmin molecule. The phosphorylation may cause the functional loss of stathmin
      for dynamic microtubule assembly and leads Jurkat cells to cell cycle arrest and
      apoptosis.

PMID- 16427065
TI  - Separation of technical 4-nonylphenols and their biodegradation products by
      comprehensive two-dimensional gas chromatography coupled to time-of-flight mass
      spectrometry.
AB  - Comprehensive two-dimensional gas chromatography (GC x GC) coupled to time-of
      flight mass spectrometry (TOF-MS) was applied to improve the separation of 4
      nonylphenol isomers and their biodegradation products. The structurally similar
      nonylphenol isomers were separated by combining a 30 m long semi-polar column and
      a short polar capillary. Both were coupled via a custom-made liquid nitrogen
      cryogenic modulator. The advanced GC resolution of coeluting isomers,
      additionally supported by fast scanning TOF-MS, provided clearer, non-interfered
      mass spectra of individual isomers. Thus, identification of components is
      facilitated as shown for isomeric 4-nonylphenols and metabolites of their
      biodegradation by Clavariopsis aquatica, an aquatic fungus. GC x GC-TOF-MS
      analysis enabled the separation of about 40 alkylphenol isomers included in
      technical 4-nonylphenol. During biodegradation the variety of emerging compounds
      increased with longer reaction time. The comprehensive analysis indicated a broad
      spectrum of hydroxylated, carboxylated nonylphenolisomers and additionally,
      chlorinated aromatic compounds produced and released from the fungal culture.

PMID- 16427066
TI  - Morphology control of poly(vinylidene fluoride) thin film made with electrospray.
AB  - Thin polymer films of poly(vinylidene fluoride) were prepared with electrospray.
      Effects of solvent, initial spray concentration, temperature, solution
      conductivity, and polymer size on the film morphology were studied with AFM. The
      two main factors controlling polymer film morphology are the droplet size of the
      spray and the viscosity of the solution at deposition. These factors determine
      the flow of the polymer-solvent mixture over the substrate, the density of the
      film, and its smoothness. The solvent is a key parameter of the entire process.
      It affects spray stability, polymer solubility, droplet size of the spray, and
      viscosity of the solution at deposition. Solvents with a low vapor pressure
      provide a wider window for optimization of other parameters and are therefore
      preferred over solvents with high vapor pressure. The viscosity at deposition is
      mainly controlled with the initial spray concentration, polymer size,
      temperature, and droplet size. The droplet size is best controlled by the
      conductivity of the solution and the flow rate of the spray.

PMID- 16427067
TI  - Flux-assisted wetting and spreading of Al on TiC.
AB  - The effect of a K-Al-F-based flux on the spreading of Al on TiC, at temperatures
      up to 900 degrees C, in Ar and in air has been studied. Whilst obtuse contact
      angles were observed without flux, the flux facilitated rapid spreading to a
      perfect wetting condition, in both Ar and in air. The atmosphere was found to
      have a weak effect on the spreading kinetics as the liquid flux provides a
      locally protective atmosphere by spreading over the TiC surface and also on the
      solid surface of Al. The flux dissolves the aluminium oxide, covering Al, so that
      when Al melts, and the oxide layer has been removed or weakened, intimate contact
      occurs between liquid Al and the TiC substrate facilitating spontaneous spreading
      and instantaneous wetting of liquid Al on TiC. Since flux-assisted spreading is
      very rapid and occurs without the formation of a reaction layer at the Al/TiC
      interface, this process is very different to the reactive wetting behaviour
      previously reported in the Al-TiC system.

PMID- 16427068
TI  - Simple models of adsorption in nanotubes.
AB  - We present two very simple models of adsorption in cylindrical pores. It is
      assumed that a layer-by-layer mechanism occurs similarly to that in the BET
      theory. The major assumption is that in the pores having an adsorption space with
      cylindrical geometry, the surface area of the upper surface (in comparison with
      the bottom surface) should be diminished in proportion to the radii of a
      cylinder. Two cases are considered: the adsorbate-adsorbate interactions are
      neglected or they are taken into account according to the lattice model developed
      by Fowler and Guggenheim. It is shown that the data simulated by Ohba and Kaneko
      for adsorption of nitrogen in the internal space of carbon nanotubes are
      successfully described by our models. On the basis of the fitted data we show
      that the relation between the monolayer capacity in cylindrical pores and on flat
      surfaces is in excellent agreement with the equation developed recently by Salmas
      and Androutsopoulos. Moreover, our models are verified for two sets of
      experimental data reported by Kaneko et al. We obtain excellent agreement between
      the values of the pore diameters calculated by us and suggested by these authors
      (from HRTEM, the GCMC simulations, and the IDBdB model). It is concluded that
      proposed simple and fast models can be applied as a first approximation to the
      estimation of the internal nanotube diameters if they do not exceed ca. 5 nm and
      are slightly dispersed.

PMID- 16427069
TI  - Alumina interaction with AMPS-MPEG random copolymers III. Effect of PEG segment
      length on adsorption, electrokinetic and rheological behavior.
AB  - The effect of different 2-acrylamido-2-methylpropanesulfonic acid sodium salt
      (AMPS)-methoxypolyethyleneglycol methacrylate (MPEG) comb-like copolymers on the
      adsorption behavior, electrokinetic and rheological properties of alumina
      suspensions has been investigated. The change in adsorption isotherms with the
      content of the two monomers, the medium pH and the ionic strength indicated that
      the interaction of these copolymers was found to be controlled by both the
      fraction of ionic groups on the polymer and by the length of the
      polyethyleneglycol (PEG) segments. Adsorption of the copolymers on alumina
      particles is accompanied by a shift in the IEP toward acid pH values and may lead
      to a charge reversal above a certain level. The presence of the PEG segment
      equally affects the magnitude of the zeta potential by moving the shear plane
      forward. Addition of the copolymers greatly affects the rheological behavior of
      the suspension; the viscosity at a defined shear rate decreases and reaches an
      optimum, which is all the lower as the fraction of the ionic groups is higher.
      The dispersing effect of the copolymer was controlled by both the ionization
      level of the copolymer and by the length of the PEG segments.

PMID- 16427070
TI  - Model analysis of the colloid and radionuclide retardation experiment at the
      Grimsel Test Site.
AB  - The colloid and radionuclide retardation experiments performed at NAGRA's Grimsel
      Test Site in Switzerland are part of an international collaboration program
      designed to collect in situ data on the impacts of colloids on radionuclide
      transport. In this work, breakthrough behaviors of trivalent americium (i.e.,
      241Am and 243Am) both in the absence and presence of bentonite colloids are
      analyzed with COLFRAC--a code that models colloid-facilitated solute transport in
      discretely-fractured, porous media. Model fits to the experimental results
      indicate that Am sorbed onto mobile colloids, which enhance Am transport relative
      to a non-sorbing tracer, 131I. Modelling results suggest that Am is kinetically
      sorbed onto both naturally occurring and exogenous bentonite colloids. Results
      also indicate that desorption of Am from colloids is slow with respect to the
      duration of the experiment. In addition, early colloid breakthrough compared to a
      conservative tracer suggests the effects of hydrodynamic chromatography. Overall,
      Am breakthrough curves suggest enhanced mobility due to co-transport with both
      naturally occurring and bentonite colloids.

PMID- 16427071
TI  - Immunoproteomic characterization of Brucella abortus 1119-3 preparations used for
      the serodiagnosis of Brucella infections.
AB  - The diagnosis of brucellosis is mainly based on the detection of anti-LPS
      antibodies. Due to substantial similarity of the O-polysaccharide of Brucella LPS
      to that of various other Gram-negative bacteria, serological tests of samples
      containing high amounts of LPS lack specificity. Hence, the development of assays
      based on more specific protein antigens is an essential subject in brucellosis
      research. The aim of this study was proteomic characterization of various antigen
      preparations of the diagnostic reference strain Brucella abortus 1119-3 and the
      identification of immunogenic proteins suitable for serological assays. Seventeen
      out of 383 protein spots of B. abortus 1119-3 were identified to be immunogenic
      by 2-D immunoblotting. These immunogenic spots were assigned to 6 proteins by
      MALDI-MS and nLC-ESI-MS/MS: Cu-Zn SOD, BCSP31, L7/L12, GroEL, GroES, and DnaK.
      All immunogenic proteins were present in three different antigen preparations
      investigated, i.e. native antigen, standard agglutination and commercially
      available agglutination antigen. 2-D immunoblotting of bacteria cross-reacting
      with Brucellae in agglutination tests proved that cross-reactivity of proteins is
      negligible. Surface enhanced laser desorption/ionization mass spectrometry (SELDI
      MS) spectra also differentiated B. abortus clearly from cross-reacting bacteria.
      The combination of SELDI-MS analysis with the specificity of antibody binding
      will improve the identification of Brucella specific immunogenic proteins.

PMID- 16427072
TI  - Correlation of stylet activities by the glassy-winged sharpshooter, Homalodisca
      coagulata (Say), with electrical penetration graph (EPG) waveforms.
AB  - Glassy-winged sharpshooter, Homalodisca coagulata (Say), is an efficient vector
      of Xylella fastidiosa (Xf), the causal bacterium of Pierce's disease, and leaf
      scorch in almond and oleander. Acquisition and inoculation of Xf occur sometime
      during the process of stylet penetration into the plant. That process is most
      rigorously studied via electrical penetration graph (EPG) monitoring of insect
      feeding. This study provides part of the crucial biological meanings that define
      the waveforms of each new insect species recorded by EPG. By synchronizing AC EPG
      waveforms with high-magnification video of H. coagulata stylet penetration in
      artifical diet, we correlated stylet activities with three previously described
      EPG pathway waveforms, A1, B1 and B2, as well as one ingestion waveform, C.
      Waveform A1 occured at the beginning of stylet penetration. This waveform was
      correlated with salivary sheath trunk formation, repetitive stylet movements
      involving retraction of both maxillary stylets and one mandibular stylet,
      extension of the stylet fascicle, and the fluttering-like movements of the
      maxillary stylet tips. Waveform B1 was ubitquious, interspersed throughout the
      other waveforms. B1 sub-type B1w was correlated with salivation followed by
      maxillary tip fluttering. This tip fluttering also occurred before and during B1
      sub-type B1s, but was not directly correlated with either the occurrence or
      frequency of this waveform. Waveform B2 was correlated with sawing-like maxillary
      stylet movements, which usually occurred during salivary sheath branching.
      Waveform C was correlated with ingestion. Fluid outflow was also observed as a
      mechanism to clear the maxillary tips from debris during waveform C. This
      detailed understanding of stylet penetration behaviors of H. coagulata is an
      important step toward identifying the instant of bacterial inoculation which, in
      turn, will be applied to studies of disease epidemiology and development of host
      plant resistance.

PMID- 16427073
TI  - RNAi studies reveal a conserved role for RXR in molting in the cockroach
      Blattella germanica.
AB  - Ecdysteroids play a major role during developmental growth in insects. The more
      active form of these hormones, 20-hydroxyecdysone (20E), acts upon binding to its
      heterodimeric receptor, formed by the two nuclear receptors, EcR and RXR/USP.
      Functional characterization of USP has been exclusively conducted on the
      holometabolous insect Drosophila melanogaster. However, it has been impossible to
      extend such analysis to primitive-hemimetabolous insects since species of this
      group are not amenable to genetic analysis. The development of methodologies
      based on gene silencing using RNA interference (RNAi) after treatment with double
      stranded RNA (dsRNA) in vivo has resolved such limitations. In this paper, we
      show that injection of dsRNA into the haemocoel of nymphs and adults of the
      cockroach Blattella germanica can be used to silence gene function in vivo. In
      our initial attempt to test RNAi techniques, we halted the expression of the
      adult-specific vitellogenin gene. We then used the same technique to silence the
      expression of the B. germanica RXR/USP (BgRXR) gene in vivo during the last
      nymphal instar. BgRXR knockdown nymphs progressed through the instar correctly
      but they arrested development at the end of the stage and were unable to molt
      into adults. The results described herein suggest that RXR/USP function, in
      relation to molting, is conserved across the insect Class.

PMID- 16427074
TI  - Oxygen-sensitive guanylyl cyclases in insects and their potential roles in oxygen
      detection and in feeding behaviors.
AB  - Responses to hypoxia and hyperoxia depend critically on the ability of the animal
      to detect changes in O2 levels. However, it has only been recently that an O2
      sensing system has been identified in invertebrates. Evidence is accumulating
      that this molecular O2 sensor is, surprisingly, a class of soluble guanylyl
      cyclase (sGC) known as atypical sGCs. It has long been known that the
      conventional sGC alpha and beta subunits form heterodimeric enzymes that are
      potently activated by NO, but do not bind O2. By contrast, the Drosophila
      melanogaster atypical sGC subunits, Gyc-88E, Gyc-89Da and Gyc-89Db, are only
      slightly sensitive to NO, but are potently activated under hypoxic conditions.
      Here we review evidence that suggests that the atypical sGCs can function as
      molecular O2 sensors mediating behavioral responses to hypoxia. Sequence
      comparisons of other predicted O2-sensitive sGCs suggest that most, if not all,
      insects express two heterodimeric sGCs; an NO-sensitive isoform and a separate O2
      sensitive isoform. Expression data and recent experiments that block the function
      of cells that express the atypical sGCs and experiments that reduce the cGMP
      levels in these cells also suggest a role in behavioral responses to sweet
      tastants.

PMID- 16427075
TI  - Cross-talk between bone morphogenetic protein 2 and leukemia inhibitory factor
      through ERK 1/2 and Smad1 in protection against doxorubicin-induced injury of
      cardiomyocytes.
AB  - The survival of cardiomyocytes is regulated by growth factors and cytokines such
      as bone morphogenetic protein (BMP) 2 and leukemia inhibitory factor (LIF). BMP2
      and LIF induce distinct signal transduction pathways that each activate a
      different transcription factor [Smad1 and signal transducing activating
      transcriptional factor (Stat) 3, respectively] and common signal pathway [mitogen
      activated protein kinase (MAPK)]. We previously demonstrated that BMP2 and LIF
      protect cardiomyocytes via Smad1 and STAT3 signaling pathways, respectively. On
      the other hand, these signals are known to act in synergy via synergistic
      integration of signaling pathways. Here, we examined interaction between BMP2 and
      LIF in primary cultured neonatal rat cardiomyocytes. LIF sustained
      phosphorylation/activation of Smad1 by BMP2. The role of extracellular signal
      regulated kinase (ERK) 1/2 cascade activated by LIF was highlighted by the use of
      a MAPK/ERK kinase (MEK) 1/2 inhibitor, U0126, or overexpression of dominant
      negative form of MEK1 that abolished sustained phosphorylation of Smad1 and cell
      survival effect induced by co-stimulation of LIF with BMP2, while BMP2 alone did
      not activate ERK1/2. Conversely, overexpression of the constitutive-active form
      of MEK1 increased BMP2-induced phosphoration of Smad1 without additional LIF.
      Moreover, BMP2 and LIF synergistically induced bcl-xL mRNA in doxorubicin (DOX)
      injured cardiomyocytes. These findings suggest that the ERK1/2 pathway downstream
      of LIF is involved in sustained phosphorylation/activation of Smad1 by BMP2 and
      provide a possible mechanism for cooperation between intracellular signals
      activated by LIF and BMP2 in protection against DOX-induced injury of
      cardiomyocytes.

PMID- 16427076
TI  - Caspase-3 mediated cleavage of MEKK1 promotes p53 transcriptional activity.
AB  - Myocardial ischemia/reperfusion (IR) induces myocyte apoptosis, and the pro
      apoptotic/tumor suppressor protein p53 may contribute to this process. However,
      the signaling mechanism by which IR induces p53 activation remains largely
      unknown. Here, we show that MEKK1 undergoes proteolytic cleavage in a caspase-3
      dependent manner in both in vivo and in vitro models of ischemic injury.
      Overexpression studies both in vivo and in vitro indicated that the caspase-3
      mediated cleavage of MEKK1 promotes phosphorylation and transcriptional activity
      of p53. In addition, caspase-3 inhibited the ability of the wild-type full-length
      form of MEKK1 to activate ATF2, suggesting that caspase-3, by way of proteolytic
      cleavage, abrogates the ability of MEKK1 to signal JNK. We propose that IR
      induces caspase-3 mediated proteolytic cleavage of MEKK1 and promotes p53
      transcriptional activity via JNK-independent mechanisms, which in turn may
      contribute to pathological insults associated with IR injury, such as myocyte
      apoptosis.

PMID- 16427077
TI  - Functional remodeling in post-myocardial infarcted rats: focus on beta
      adrenoceptor subtypes.
AB  - Cellular electrophysiological remodeling of the infarcted heart may lead to the
      deterioration of cardiac function and/or to arrhythmias. The present study was
      designed to characterize the functional expression of the hyperpolarization
      activated current (I(f)) and its modulation by beta(1)-, beta(2)- and beta(3)
      adrenoceptor (AR) subtypes, in patch-clamped ventricular myocytes isolated from
      the heart of post-myocardial infarcted (PMI) rats and sham-operated control
      (SHAM) rats. Maximum specific conductance of I(f) was significantly higher in
      left ventricular myocytes (LVM) from PMI rats compared to right ventricular
      myocytes from PMI rats as well as LVM and RVM from SHAM rats. All other basic
      properties of I(f) were similar. beta(1)AR stimulation with noradrenaline caused
      a rightward shift of V(H) in LVM from PMI rats which was significantly smaller
      (52.2%) than in LVM from SHAM rats. Incubation with pertussis toxin (PTX) largely
      restored the effect of beta(1)AR in PMI cells (86.6% vs. SHAM cells), but did not
      affect beta(1)AR response in SHAM cells. beta(2)AR response was significantly and
      equally increased by PTX-pretreatment (by 94% in SHAM and 87% in PMI cells).
      Conversely, beta(3)AR stimulation by the selective agonist SR 58611A caused a
      leftward shift of the activation curve which was significantly larger in PMI
      cells than in SHAM cells (P<0.01). beta(3)AR response was blunted by PTX
      pretreatment, by incubation with N(G)-monomethyl-l-arginine acetate or by the
      selective beta(3)AR antagonist SR 59230A 1 microM. In conclusion, I(f) is
      significantly overexpressed in LVM from PMI rat hearts. In these cells, I(f)
      modulation by beta(1)AR is significantly depressed while beta(3)AR modulation is
      markedly enhanced, probably reflecting the increased activity of PTX-sensitive
      G(i) proteins in PMI cells.

PMID- 16427078
TI  - Early effects of topoisomerase I inhibition on RNA polymerase II along
      transcribed genes in human cells.
AB  - We have determined the early effects of camptothecin and alpha-amanitin on
      genomic DNA-binding sites of RNA polymerase II (RNAPII), TATA-binding protein
      (TBP), DNA topoisomerase I (Top1), and histone components in human transcribed
      loci by chromatin-immunoprecipitation (ChIP). The two agents caused notably
      different alterations in active chromatin. Camptothecin induced a specific
      reduction of RNAPII density at promoter pause sites and histone modifications
      suggesting an increased chromatin accessibility. alpha-Amanitin caused an
      accumulation of RNAPII at transcribed genes, a reduction of TBP bound to
      chromatin and a less accessible chromatin structure. Interestingly, RNAPII
      reduction at promoter pause sites occurred within 5-10min of camptothecin
      treatment, and was not a response to replication-dependent DNA breaks. ChIP
      analyses of RNAPII along transcribed genes indicated that RNAPII levels were
      transiently increased at internal exons, and that camptothecin effects could be
      fully reversed by DRB, a cdk inhibitor. Top1 was found to be enriched in active
      chromatin, therefore suggesting that Top1 inhibition at the transcribed template
      and/or adjacent regulating regions immediately affects RNAPII at active genes.
      The findings are novel in vivo evidence of camptothecin effects on RNAPII bound
      to transcribing genomic regions, and are consistent with the hypothesis that Top1
      activity can be involved in transcription regulation at the level of promoter
      clearance.

PMID- 16427079
TI  - Alternate interfaces may mediate homomeric and heteromeric assembly in the
      transmembrane domains of SNARE proteins.
AB  - The fusion of a vesicle to a target membrane is mediated by temporally and
      spatially regulated interactions within a set of evolutionarily conserved
      proteins. Integral to proper fusion is the interaction between proteins
      originating on both vesicle and target membranes to form a protein bridge between
      the two membranes, known as the SNARE complex. This protein complex includes the
      single-pass transmembrane helix proteins: syntaxin and synaptobrevin.
      Experimental data and amino acid sequence analysis suggest that an interface of
      interaction is conserved between the transmembrane regions of the two proteins.
      However, conflicting reports have been presented on the role of the synaptobrevin
      transmembrane domain in mediating important protein-protein interactions. To
      address this question, a thermodynamic study was carried out to determine
      quantitatively the self-association propensities of the transmembrane domains of
      synaptobrevin and syntaxin. Our results show that the transmembrane domain of
      synaptobrevin has only a modest ability to self-associate, whereas the
      transmembrane domain of syntaxin is able to form stable homodimers. Nevertheless,
      by a single amino acid substitution, synaptobrevin can be driven to dimerize with
      the same affinity as syntaxin. Furthermore, crosslinking studies show that
      dimerization of synaptobrevin is promoted by oxidizing agents. Despite the
      presence of a conserved cysteine residue in the same location as in
      synaptobrevin, syntaxin dimerization is not promoted by oxidization. This
      analysis suggests that subtle yet distinct differences are present between the
      two transmembrane dimer interfaces. A syntaxin/synaptobrevin heterodimer is able
      to form under oxidizing conditions, and we propose that the interface of
      interaction for the heterodimer may resemble the homodimer interface formed by
      the synaptobrevin transmembrane domain. Computational analysis of the
      transmembrane sequences of syntaxin and synaptobrevin reveal structural models
      that correlate with the experimental data. These data may provide insight into
      the role of transmembrane segments in the mechanism of vesicle fusion.

PMID- 16427080
TI  - Thioredoxin fusions increase folding of single chain Fv antibodies in the
      cytoplasm of Escherichia coli: evidence that chaperone activity is the prime
      effect of thioredoxin.
AB  - In this study we investigate the effect of thioredoxin (Trx1) protein fusions in
      the production, oxidation, and folding of single chain Fv (scFv) antibodies in
      the cytoplasm of Escherichia coli. We analyze the expression levels, solubility,
      disulfide-bond formation, and antigen-binding properties of Trx1-scFv fusions in
      E. coli wild-type cells and isogenic strains carrying mutations in the
      glutathione oxidoreductase (gor) and/or thioredoxin reductase (trxB) genes. We
      compare the Trx1-scFv fusions with other reported systems for production of scFv
      in the cytoplasm of E. coli, including protein fusions to the maltose-binding
      protein. In addition, we analyze the effect of co-expressing a signal-sequence
      less derivative of the periplasmic chaperone and disulfide-bond isomerase DsbC
      (DeltassDsbC), which has been shown to act as a chaperone for scFvs in the
      cytoplasm. The results reported here demonstrate that Trx1 fusions produce the
      highest expression level and induce the correct folding of scFvs even in the
      absence of DeltassDsbC in the cytoplasm of E. coli trxB gor cells. The disulfide
      bridges of Trx1-scFv fusions were formed correctly in E. coli trxB gor cells, but
      not in trxB single mutants. Antigen-binding assays showed that Trx1 has only a
      minor influence in the affinity of the scFv, indicating that Trx1-scFv fusions
      can be used without removal of the Trx1 moiety. In addition, we proved that a
      Trx1"AGPA" variant, having its catalytic cysteine residues mutated to alanine,
      was fully capable of assisting the folding of the fused scFvs. Taken together,
      our data indicate that the Trx1 moiety acts largely as an intramolecular protein
      chaperone, not as a disulfide bond catalyst, inducing the correct folding of
      scFvs in the cytoplasm of E. coli trxB gor cells.

PMID- 16427081
TI  - Crystal structures of an enantioselective fab-fragment in free and complex forms.
AB  - Enantioselective antibodies can separate the enantiomers of a chiral compound in
      a highly specific manner. We have recently reported the cloning and applications
      of a recombinant Fab-fragment, ENA11His, in the enantioseparation of a drug
      candidate, finrozole, which contains two chiral centers. Here, the crystal
      structures of this enantioselective antibody Fab-fragment are determined in the
      absence of the hapten at a resolution of 2.75 A, and in the presence of the
      hapten at 2.05 A resolution. The conformation of the protein was found to be
      similar in both free and complex forms. The hapten molecule was tightly bound in
      a deep cleft between the light and heavy chains of the Fab-fragment. The complex
      structure also allowed us to describe the molecular basis for enantioselectivity
      and to deduce the absolute configurations of all the four different stereoisomers
      (a-d) of finrozole. The ENA11His antibody fragment selectively binds the SR (a)
      enantiomer from the racemic mixture of a and d-enantiomers, thus allowing
      separation from the pharmacologically most active RS enantiomer (d). In
      particular, Asp95 and Asn35 of the H-chain in the ENA11 His antibody seem to
      provide this specificity through hydrogen bonding.

PMID- 16427082
TI  - Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex:
      recognition of pyrimidine-purine and purine-purine steps.
AB  - The catabolite activator protein (CAP) bends DNA in the CAP-DNA complex,
      typically introducing a sharp DNA kink, with a roll angle of approximately 40
      degrees and a twist angle of approximately 20 degrees, between positions 6 and 7
      of the DNA half-site, 5'-A1A2A3T4G5T6G7A8T9C10T11 -3' ("primary kink"). In
      previous work, we showed that CAP recognizes the nucleotide immediately 5' to the
      primary-kink site, T6, through an "indirect-readout" mechanism involving sequence
      effects on energetics of primary-kink formation. Here, to understand further this
      example of indirect readout, we have determined crystal structures of CAP-DNA
      complexes containing each possible nucleotide at position 6. The structures show
      that CAP can introduce a DNA kink at the primary-kink site with any nucleotide at
      position 6. The DNA kink is sharp with the consensus pyrimidine-purine step T6G7
      and the non-consensus pyrimidine-purine step C6G7 (roll angles of approximately
      42 degrees, twist angles of approximately 16 degrees ), but is much less sharp
      with the non-consensus purine-purine steps A6G7 and G6G7 (roll angles of
      approximately 20 degrees, twist angles of approximately 17 degrees). We infer
      that CAP discriminates between consensus and non-consensus pyrimidine-purine
      steps at positions 6-7 solely based on differences in the energetics of DNA
      deformation, but that CAP discriminates between the consensus pyrimidine-purine
      step and non-consensus purine-purine steps at positions 6-7 both based on
      differences in the energetics of DNA deformation and based on qualitative
      differences in DNA deformation. The structures further show that CAP can achieve
      a similar, approximately 46 degrees per DNA half-site, overall DNA bend through a
      sharp DNA kink, a less sharp DNA kink, or a smooth DNA bend. Analysis of these
      and other crystal structures of CAP-DNA complexes indicates that there is a
      large, approximately 28 degrees per DNA half-site, out-of-plane component of CAP
      induced DNA bending in structures not constrained by end-to-end DNA lattice
      interactions and that lattice contacts involving CAP tend to involve residues in
      or near biologically functional surfaces.

PMID- 16427084
TI  - Detection of telomerase activity in gastric lavage fluid: a novel method to
      detect gastric cancer.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein polymerase that is essential for
      cell immortality. Recent studies have demonstrated that a high percentage of
      gastric cancer tissue expressed telomerase. This study describes the presence of
      telomerase activity in gastric lavage fluid in patients with gastric cancer.
      METHODS: Gastric lavage fluid was collected during esophageogastroduodenoscopy in
      70 patients: 25 with gastric cancer, 25 with peptic ulcer disease, and 20 with
      normal stomach. The fluid and biopsy samples were analyzed for telomerase
      activity by a polymerase chain reaction-based telomerase repeat amplification
      protocol. The findings were related to the histological results. RESULTS:
      Telomerase activity was present in 24 of the 25 (96%) gastric cancer tissue and
      in 7 of the 25 tissue specimens from peptic ulcer or gastritis. In the gastric
      lavage fluid, telomerase was detected in 20 patients (80%) with gastric cancer, 7
      patients (28%) with peptic ulcer, and none in normal subjects (P < 0.001). The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of gastric fluid telomerase expression in gastric cancer patients was 80%,
      84%, 74%, and 88%, respectively. CONCLUSIONS: The presence of telomerase activity
      is present in gastric lavage fluid of patients with gastric cancer as compared to
      those without, may represent a novel method for diagnosis of gastric cancer.

PMID- 16427083
TI  - Nucleotide channel of RNA-dependent RNA polymerase used for intermolecular
      uridylylation of protein primer.
AB  - Poliovirus VPg is a 22 amino acid residue peptide that serves as the protein
      primer for replication of the viral RNA genome. VPg is known to bind directly to
      the viral RNA-dependent RNA polymerase, 3D, for covalent uridylylation, yielding
      mono and di-uridylylated products, VPg-pU and VPg-pUpU, which are subsequently
      elongated. To model the docking of the VPg substrate to a putative VPg-binding
      site on the 3D polymerase molecule, we performed a variety of structure-based
      computations followed by experimental verification. First, potential VPg folded
      structures were identified, yielding a suite of predicted beta-hairpin
      structures. These putative VPg structures were then docked to the region of the
      polymerase implicated by genetic experiments to bind VPg, using grid-based and
      fragment-based methods. Residues in VPg predicted to affect binding were
      identified through molecular dynamics simulations, and their effects on the 3D
      VPg interaction were tested computationally and biochemically. Experiments with
      mutant VPg and mutant polymerase molecules confirmed the predicted binding site
      for VPg on the back side of the polymerase molecule during the uridylylation
      reaction, opposite to that predicted to bind elongating RNA primers.

PMID- 16427085
TI  - The structural and cellular viability in cryopreserved rabbit carotid arteries.
AB  - OBJECTIVE: We investigated the histological and mechanical changes in addition to
      viable cellular recovery in cryopreserved blood vessels. MATERIALS AND METHODS:
      Rabbit carotids were cryopreserved in a cryoprotective medium containing 1.5 M of
      1,2-propanediol (PD) and then were thawed slowly in an ice bag that had been
      precooled in liquid nitrogen. Fresh carotids were used as the control. The fresh
      and freeze-thawed arteries were cultured for the growth of vascular smooth muscle
      cells (VSMCs). The freeze-thawed arterial tissues were perfused in vitro for 6,
      12, or 24 h, respectively, to assess the integrity of carotid walls and the
      mechanical properties. RESULTS: The results showed that it took almost the same
      time (24 approximately 36 h) for the VSMCs of the PD-cryopreserved arteries to
      regenerate as those from the fresh arteries. Their growing speeds also were
      similar. On the contrary, Me2SO-cryopreserved (1.5 M) arteries were unable to
      regenerate VSMCs in culture. After freeze-thawing, the mechanical properties
      decreased significantly (P < 0.003 for elastic modulus and P < 0.001 for fracture
      strength). After in vitro perfusion of the freeze-thawed carotid arteries, all of
      the survived endothelial cells fell off, and some of the VSMCs denaturalized or
      necrosed. The internal elastic fibers and collagen showed various degrees of
      cracking. The mechanical properties were decreased (P < 0.05). CONCLUSION: Our
      findings demonstrate that the PD-containing cryoprotective medium can preserve
      regenerative capacity of VSMCs, which makes it a useful technique for viable VSMC
      recovery. However, the freeze-thawing process and the in vitro perfusion caused
      serious disruption in the arterial mechanical properties, rendering the
      cryopreserved blood vessels less useful for vessel reconstruction.

PMID- 16427086
TI  - Intraoperative radiofrequency ablation using a loop internally cooled-perfusion
      electrode: in vitro and in vivo experiments.
AB  - OBJECTIVE: We sought to validate the efficiency of intraoperative radiofrequency
      ablation (RFA) using a prototype loop internally cooled-perfusion (LICP)
      electrode to induce coagulation in the subcapsular portion of the liver.
      MATERIALS AND METHODS: In in vitro experiments, 30 ablation regions were created
      using a 200-W generator and a LICP electrode featured simultaneous intraelectrode
      cooling and continuous flow of hypertonic saline along the shaft in explanted
      bovine liver. In the in vivo experiments, 26 ablation zones were created
      according to one of the five protocols in 10 dogs: group A, RFA using a cooled
      tip electrode (n = 6); group B, RFA using a LICP electrode with 2 cm loop tip (n
      = 6); group C, RFA using a LICP electrode with a 3-cm loop tip (n = 6); group D,
      RFA using a cooled-tip electrode and Pringle maneuver (n = 4); and group E, RFA
      using a LICP electrode with 2 cm loop tip and Pringle maneuver (n = 4). The
      dimensions of the coagulation parameters were compared between the groups.
      RESULTS: In the in vitro experiments, RFA using a 2- or 3-cm diameter LICP
      electrode (3.6 +/- 0.3 cm, 3.4 +/- 0.5 cm, respectively) created deeper
      dimensions of coagulation than did a 4-cm electrode (2.3 +/- 0.2 cm; P < 0.05).
      In the in vivo experiments, the RFA using the LICP electrodes in porcine liver
      with normal perfusion induced wider but superficial ablation regions when
      compared to standard RFA using an internally cooled electrode (P < 0.05).
      However, using a Pringle maneuver, RFA with a LICP electrode created a larger
      volume of ablation area when compared to RFA using an internally cooled electrode
      with a similar range of axial diameter along the electrode axis: 30.0 +/- 6.1 cm3
      (group D) versus 68.5 +/- 14.0 cm3 (group E; P < 0.05) CONCLUSIONS:
      Intraoperative RFA using the LICP electrode induced a well-defined semicircular
      coagulation with a 3.5-cm axial diameter in the subcapsular region of the liver.
      This device appears to be promising for the treatment of superficial tumors
      during intraoperative RFA.

PMID- 16427087
TI  - Intermittent alveolar overdistension for 30 or 240 minutes does not produce acute
      lung injury in normal pig lung.
AB  - BACKGROUND: The objective is to study whether alveolar overdistension can induce
      acute lung injury in pigs as assessed by analysis of respiratory and histological
      parameters and inflammatory markers. MATERIALS AND METHODS: Experimental study,
      using mixed-breed pigs. Animals were assigned to one of the following groups:
      Control Group (CG) (n = 5), applying mechanical ventilation with tidal volume
      (Vt) of 10 ml/kg, respiratory rate (RR) of 18 bpm, and FiO2 of 1 for 240 min;
      High Vt for 30 min (HVt-30) Group (n = 5), applying ventilation with Vt of 50
      ml/kg and RR of 8 bpm and FiO2 of 1 for 30 min, followed by ventilation as in the
      CG for a further 210 min; and HVt-240 Group (n = 5), applying ventilation with Vt
      of 50 ml/kg, RR of 8 bpm, and FiO2 of 1 for 240 min. Hemodynamic parameters,
      airway pressures, arterial blood gases, extravascular lung water (EVLW), and
      cytokines (IL-2, IL-4, IL-6, IL-10, TNF-alpha, and ITF-gamma) in plasma and
      bronchoalveolar lavage (BAL) were determined. Lungs were fixed with 10% formalin
      for histological analysis. Results are expressed as mean +/- standard deviation.
      The ANOVA test was used to compare measurements among the three groups. RESULTS:
      At 30 min, airway pressures and oxygenation of HVt-30 and HVt-240 groups were
      higher than those of controls [Pplateau: 39.2 +/- 5.6 and 33.0+/- 5.1 versus 12.2
      +/- 1.3 (P < 0.01); PaO2/FiO2: 443.8 +/- 55 and 430.6 +/- 34 versus 194.4 +/- 77
      (P < 0.01)]. In HVt-240 group, these parameters were also higher than in the
      other two groups at the subsequent measurement times. There were no differences
      among the groups in EVLW values. Cytokines were undetected or negligible in
      plasma and BAL in all of the groups. The histological analysis showed no changes
      suggestive of acute lung injury. CONCLUSIONS: In this animal model, ventilation
      for 4 h with large tidal volume did not cause ventilator-induced lung injury.

PMID- 16427088
TI  - Quantitative studies of liver atrophy after portacaval shunt in the rat.
AB  - BACKGROUND: It is well known that portacaval shunting ultimately leads to a
      decrease in liver volume and hepatic function, but the mechanism is uncertain.
      The aim of the present study was to evaluate the effect of portacaval shunting
      (PCS) upon the morphological changes that occur in the liver in rats after port
      caval anastomosis. MATERIALS AND METHODS: Sixty-six male rats underwent either
      PCS (n = 35) or sham operations (n = 31). Hormone levels were determined in blood
      samples taken just before removal and weighing of the livers. Hematoxylin and
      eosin-stained sections were used for quantitative morphometric analysis.
      Apoptosis, mitosis, and cellular organelles also were assessed quantitatively.
      RESULTS: There was a significant reduction in the liver mass together with
      testosterone levels in PCS rats in comparison with sham rats. The distance
      between presinusoidal and postsinusoidal vessels was reduced from 500 mum in the
      sham rats to 299 mum in the PCS rats (P = 0.000001). Within the same group, there
      was a significant reduction in the area of hepatocyte nuclei in zone 3 in
      comparison with zone 1. Electron microscopy revealed a highly significant (P =
      0.0007) reduction in the membrane-bound cytoplasmic organelles of zone 3
      hepatocytes in PCS rats in comparison with the sham rats. Apoptosis was increased
      in zone 3 in PCS rats (P = 0.00001), whereas in zone 1 of the same group, there
      was an associated increased in mitosis (P = 0.000001). Overall, the degree of
      apoptosis was in excess of mitosis, resulting in a general loss of liver mass.
      CONCLUSION: Morphometric analysis at cellular and subcellular levels confirms the
      morphological findings of liver atrophy in PCS rats. The mechanism of atrophy is
      a complex one. Portacaval shunting leads to hepatic atrophy that, in turn,
      results in microcirculatory and hormonal changes that further contribute to liver
      cell loss in this animal model.

PMID- 16427089
TI  - Exploring synonymous codon usage preferences of disulfide-bonded and non
      disulfide bonded cysteines in the E. coli genome.
AB  - High-quality data about protein structures and their gene sequences are essential
      to the understanding of the relationship between protein folding and protein
      coding sequences. Firstly we constructed the EcoPDB database, which is a high
      quality database of Escherichia coli genes and their corresponding PDB
      structures. Based on EcoPDB, we presented a novel approach based on information
      theory to investigate the correlation between cysteine synonymous codon usages
      and local amino acids flanking cysteines, the correlation between cysteine
      synonymous codon usages and synonymous codon usages of local amino acids flanking
      cysteines, as well as the correlation between cysteine synonymous codon usages
      and the disulfide bonding states of cysteines in the E. coli genome. The results
      indicate that the nearest neighboring residues and their synonymous codons of the
      C-terminus have the greatest influence on the usages of the synonymous codons of
      cysteines and the usage of the synonymous codons has a specific correlation with
      the disulfide bond formation of cysteines in proteins. The correlations may
      result from the regulation mechanism of protein structures at gene sequence level
      and reflect the biological function restriction that cysteines pair to form
      disulfide bonds. The results may also be helpful in identifying residues that are
      important for synonymous codon selection of cysteines to introduce disulfide
      bridges in protein engineering and molecular biology. The approach presented in
      this paper can also be utilized as a complementary computational method and be
      applicable to analyse the synonymous codon usages in other model organisms.

PMID- 16427090
TI  - Modeling segmental patterning in Drosophila: Maternal and gap genes.
AB  - We propose a new mathematical model describing the establishment of maternal and
      gap proteins segmental patterning along the antero-posterior axis of the
      Drosophila early embryo. This model is based on experimental data and, without
      recurring to pre-defined activation thresholds, predicts qualitatively and
      quantitatively the expression patterns of the maternal and gap proteins, as well
      as the expression patterns of proteins resulting from mRNA ectopic expression and
      from some loss-of-function mutations. We conclude that the gap genes segmental
      patterning and consequent spatial organization of the embryo is determined by
      three main factors: (1) the initial positioning of the maternal bicoid and torso
      mRNA inside the egg, and subsequent diffusion of the corresponding proteins; (2)
      the structure of the genetic regulatory network; (3) the role of conservation
      laws in the establishment of steady and non-uniform spatial distributions of non
      diffusing proteins.

PMID- 16427091
TI  - Evidence-based drug--herbal interactions.
AB  - Due to the growing use of herbals and other dietary supplements healthcare
      providers and consumers need to know whether problems might arise from using
      these preparations in combination with conventional drugs. However, the evidence
      of interactions between natural products and drugs is based on known or suspected
      pharmacologic activity, data derived from in vitro or animal studies, or isolated
      case reports that frequently lack pertinent information. The usefulness of such
      information is questionable. More recently an increasing number of documented
      case reports, in vivo studies, and clinical trials have evaluated herbal-drug
      interactions. Results have sometimes been contradictory and more research is
      needed. Since there is a lack of rigorous studies that can establish the clinical
      significance of herb-drug interactions, an evidence-based evaluation of the
      current literature concerning commonly used herbal-drug interactions, as well as
      other dietary supplements, was conducted.

PMID- 16427092
TI  - In vitro and in vivo assessment of herb drug interactions.
AB  - Herbal products contain several chemicals that are metabolized by phase 1 and
      phase 2 pathways and also serve as substrates for certain transporters. Due to
      their interaction with these enzymes and transporters there is a potential for
      alteration in the activity of drug metabolizing enzymes and transporters in
      presence of herbal components. Induction and inhibition of drug metabolizing
      enzymes and transporters by herbal component has been documented in several in
      vitro studies. While these studies offer a system to determine the potential for
      a herbal component to alter the pharmacokinetics of a drug, they cannot always be
      used to predict the magnitude of any potential effect in vivo. In vivo studies
      are the ultimate way to determine the clinical importance of herb drug
      interactions. However, lack of content uniformity and lack of documentation of
      the bioavailability of herbal components makes even in vivo human studies
      difficult to interpret as the effect may be product specific. It appears that St.
      John's wort extract is probably one of the most important herbal product that
      increases the metabolism and decreases the efficacy of several drugs. Milk
      thistle on the other hand appears to have minimal effect on phase 1 pathways and
      limited data exists for phase 2 pathways and transporter activity in vivo.
      Further systematic studies are necessary to assess the significance of herb drug
      interactions.

PMID- 16427093
TI  - Metalloprotease-dependent amphiregulin release mediates tumor necrosis factor
      alpha-induced IL-8 secretion in the human airway epithelial cell line NCI-H292.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent multifunctional cytokine that
      plays a central role in the pathogenesis of many inflammatory diseases.
      Interleukin-8 (IL-8) is a principle neutrophil chemoattractant and activator in
      humans. The alveolar macrophage-derived TNF-alpha initiates lung inflammation
      through its ability to stimulate IL-8 synthesis in airway epithelial cells. Since
      recent studies demonstrated that the stimulation of epidermal growth factor
      receptor (EGFR) could induce IL-8 secretion, the involvement of EGFR in TNF-alpha
      induced IL-8 secretion in airway epithelium-like NCI-H292 cells was investigated
      in this study. TNF-alpha and epidermal growth factor (EGF) stimulated IL-8
      secretion in a time- and concentration-dependent manner. Inhibition of the EGFR
      by either an anti-EGFR neutralizing antibody or by its specific inhibitor AG1478
      (1 microM) blocked TNF-alpha-induced IL-8 secretion. In addition, TNF-alpha
      stimulated tyrosine phosphorylation of the EGFR within 5 min after stimulation.
      Further, TNF-alpha-induced IL-8 secretion was completely inhibited by the
      neutralizing antibody against amphiregulin (AR), an EGFR ligand, suggesting that
      TNF-alpha-induced IL-8 secretion was mediated by the AR-EGFR pathway.
      Furthermore, TNF-alpha stimulated the release of AR in a concentration-dependent
      manner. Finally, both AR and IL-8 release-induced by TNF-alpha were eliminated by
      pretreatment with either GM6001, a broad-spectrum inhibitor for metalloprotease,
      or TAPI-1, relatively selective inhibitor for TNF-alpha converting enzyme (TACE).
      These findings indicate that metalloprotease-mediated AR shedding and subsequent
      activation of EGFR play a critical role in TNF-alpha-induced IL-8 secretion from
      the human airway epithelium-like NCI-H292 cells, and that TACE is one of the most
      possible candidates for metalloprotease responsible for TNF-alpha-induced AR
      shedding.

PMID- 16427094
TI  - Distribution of mRNA and binding sites of adrenoceptors and muscarinic receptors
      in the rat heart.
AB  - Since there exist some obscurities in the expression of mRNAs and their receptors
      in the heart, we have investigated the gene expression (mRNA levels) of
      adrenoceptors (alpha1A-, alpha1B-, beta1-, beta2-, beta3-) and muscarinic
      receptors (M2) and the density of receptor binding sites (alpha1A-, alpha1B-,
      beta1-, beta2-adrenoceptors, muscarinic receptors). Moreover, the heart regions
      consist of tissue rich in ganglion cells (that are of importance in heart neural
      circuits) and those virtually free of them (myocytes). Therefore, we have
      examined the differences in the distribution of mRNAs/receptor binding sites in
      the atrial samples of the heart rich in ganglion cells vs. those are virtually
      free of them. Binding sites and mRNAs of muscarinic receptors and alpha1B
      adrenoceptors differ in their distribution in different heart regions. The mRNAs
      for beta1- and beta2-adrenoceptors were almost equally distributed herein, while
      the amount of beta-adrenoceptors significantly differs in the heart regions. The
      alpha1A- and beta3-adrenoceptors mRNAs were also found in all investigated heart
      regions, but at significantly lower level and have not shown region differences.
      This is a new finding, especially to beta3-adrenoceptors, as they were not
      regularly found in each heart regions. alpha1B-adrenoceptors have similar
      distribution of their mRNAs and binding sites in some heart parts. Thus, we can
      conclude that there are noticeable differences in the presence of receptors in
      heart regions that contain ganglion cells in comparison to those are virtually
      free of them.

PMID- 16427095
TI  - The lack of association between monoamine oxidase (MAO) intron 13 polymorphism
      and platelet MAO-B activity among men.
AB  - Monoamine oxidase (MAO), a mitochondrial flavine containing enzyme, exists in two
      isoenzymes, MAO-A and MAO-B. Platelets contain MAO-B subtype, proposed to be a
      biomarker for different personality characteristics and vulnerability for
      substance abuse. The most common polymorphism of MAO-B gene, a single base change
      (A or G) occurs in intron 13. It has been proposed to be a functional
      polymorphism, controlling the activity of MAO-B in platelets. The aim of the
      study was to determine the association between platelet MAO-B activity and MAO-B
      intron 13 polymorphism in 225 racially and ethnically uniform healthy Caucasian
      men of the Croatian origin. Our results showed that platelet MAO-B activity did
      not differ between subjects subdivided into those with <<A-allele>> or <<G
      allele>>. This polymorphism of the MAO-B gene did not control the activity of the
      MAO-B in platelets. Platelet MAO-B activity was associated only with the smoking
      status, and it was significantly decreased in smokers when compared to
      nonsmokers. No significant association was found between MAO-B polymorphism and
      smoking status. In healthy individuals of the Croatian origin, the studied MAO-B
      polymorphism showed a lack of functional importance in regulating MAO-B activity
      in platelets. Since different populations may vary in the association between
      functional polymorphism and the MAO-B activity, and the genotype of transcription
      factor AP-2 beta was reported to be associated with altered platelet MAO-B
      activity, and with specific personality traits, further studies on different
      populations should be conducted to elucidate the molecular mechanism/s regulating
      platelet MAO-B activity.

PMID- 16427096
TI  - Water quality and fisheries in the Mersey estuary, England: A historical
      perspective.
AB  - The Mersey estuary, NW England, once had a prolific fishery but in the aftermath
      of the industrial revolution water quality and fisheries declined and the Mersey
      became infamous as one of the most polluted rivers in Europe. Until relatively
      recently, almost all industrial and domestic effluents were discharged without
      treatment resulting in abominable fouling of the shoreline, and long anoxic
      reaches in the upper estuary during the summer. In addition, there were unknown
      biological impacts resulting from a complex mixture of dangerous substances
      present in the river. Over 1000 million pound has been spent to remedy this
      situation and there is unequivocal evidence that this has had the desired effect.
      Dissolved oxygen is now generally >60% saturation, salmon are now found at the
      tidal-limit and the estuary is becoming ever more popular for sea angling. The
      river is no longer an embarrassing liability but is now perceived as an important
      asset in the economic regeneration of this region of the United Kingdom.

PMID- 16427097
TI  - HMG-CoA reductase inhibitors induce apoptosis in pericytes.
AB  - Pericytes, which surround endothelial cells in precapillary arterioles,
      capillaries, and postcapillary venules, are important for the development,
      maturation, and maintenance of the vascular system. Pericytes are also
      pluripotent cells that can differentiate into a variety of mesenchymal cells
      including smooth muscle cells and osteoblasts. Possibly because of their
      vasculature regulating activities and ability to differentiate in situ, pericytes
      are implicated in several diseases with vascular complications, including
      diabetic retinopathy, as well as Reynaud's Syndrome, central nervous system
      dementias, and vascular calcification among others. Statin drugs, which block the
      conversion of HMG-CoA to mevalonate in the cholesterol synthesis pathway, are
      known to have apoptotic and growth inhibitory effects on cells in vitro and
      complex pleiotropic effects on cells and tissues in vivo. Recently, evidence has
      emerged that statin drug use in human patients results in a significant 20%
      reduction in cancer incidence. It is not known whether these results are due to
      direct statin action on normal tissue, growth inhibitory/pro-apoptotic effects on
      tumor cells, and/or effects on angiogenesis. Because of the role of pericytes in
      angiogenesis and the effects of statins on cancer incidence, we tested the direct
      effects of statins on pericytes. Specifically, we demonstrate that 3 statins,
      simvastatin, lovastatin, and mevastatin induce dose-dependent apoptosis in the TR
      PCT1 pericyte cell line, that simvastatin (empirically shown to be the most
      potent of the 3 statins) induces similar levels of apoptosis in freshly isolated
      pericytes, and that simvastatin-induced apoptosis in pericytes is cholesterol,
      caspase-3, and caspase-7 mediated.

PMID- 16427098
TI  - Modulation of Delta(9)-THC-induced increase of cortical and hippocampal
      acetylcholine release by micro opioid and D(1) dopamine receptors.
AB  - The administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and synthetic
      cannabinoids stimulates acetylcholine (ACh) release in the rat prefrontal cortex
      (PFCx) and hippocampus as estimated by brain microdialysis. The present study was
      aimed at assessing whether the ability of Delta(9)-THC to stimulate ACh release
      is dependent upon opioid and dopamine (DA) receptors. Administration of the micro
      opioid receptor antagonists naloxone and naltrexone prevented the Delta(9)-THC
      induced release of ACh in the PFCx and hippocampus. Similarly, bilateral infusion
      in the ventral tegmental area (VTA), 24h before Delta(9)-THC, of the pseudo
      irreversible micro(1) antagonist naloxonazine completely prevented the increase
      of ACh release by Delta(9)-THC. Pre-treatment with the D(1) receptor antagonist
      SCH 39,166 reduced Delta(9)-THC-induced ACh release both in the PFCx and in the
      hippocampus. Since Delta(9)-THC has been shown to increase DA release in the
      nucleus accumbens (NAc) shell via a micro(1)-opioid receptor mediated mechanism
      located in the VTA (Tanda, G., Pontieri, F.E., Di Chiara, G., 1997. Cannabinoid
      and heroin activation of mesolimbic dopamine transmission by a common micro(1)
      opioid receptor mechanism. Science 276, 2048-2050.), we hypothesize that Delta(9)
      THC-induced stimulation of ACh release in the PFCx and hippocampus is related to
      stimulation of endogenous opioids release in the VTA with secondary activation of
      DA neurons projecting to the NAc shell.

PMID- 16427099
TI  - Syntax production in bilinguals.
AB  - We used fMRI to examine the functional correlates of syntactical processing in
      the first (L1) and second (L2) languages of non-proficient, late bilinguals.
      Subjects either covertly read words or produced sentences from them. Syntactical
      production during sentence production activated regions including left inferior
      frontal (LIFG) gyrus and the supplementary motor area in both languages. Analyses
      performed on the LIFG activation identified on a subject-by-subject basis
      revealed greater activation in L2 compared to L1 during sentence production and
      during word reading, consistent with previous work suggesting that greater
      cognitive effort may be subserved by less well-tuned neural representations that
      require greater neuronal activity. Remarkably, there was a greater separation in
      the LIFG activations in L1 versus L2 in less compared to more proficient
      bilinguals during syntax production, suggesting a functional reorganisation of
      regions involved in syntactical production as a function of syntactical
      proficiency.

PMID- 16427100
TI  - Genetic variance contributes to ingestive processes: a survey of 2-deoxy-D
      glucose-induced feeding in eleven inbred mouse strains.
AB  - The feeding response following administration of the anti-metabolic glucose
      analogue, 2-deoxy-d-glucose (2DG), is conceptualized as an experimental model of
      glucoprivation, which may contribute to the understanding of inter-individual
      differences in glucose and carbohydrate intake and, ultimately, obesity. Although
      variation in the intake of several nutrients as well as food and water are known
      to be associated with genetic variation, it is not known whether 2DG-induced
      feeding is similarly genotype dependent. The present study therefore examined 2DG
      induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ,
      C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1)
      strains across a wide range of previously determined effective 2-DG doses (200,
      400, 600, 800 mg/kg) and test times (1-4 h). Orderly dose-dependent increases in
      2DG-induced feeding occurred after all four doses in outbred CD-1 and inbred
      DBA/2J mice, across the three highest doses for BALB/cJ, SJL/J and 129P3/J mice,
      and across the two highest doses for CBA/J and AKR/J mice. Limited instances of
      2DG-induced feeding were noted only at the highest dose in A/J and C3H/HeJ mice,
      or at a moderate dose in C57BL/6J mice. Further, the full 2DG dose range failed
      to alter food intake in C57BL/10J mice, and produced significant reductions in
      food intake in SWR/J mice. Food intake after 2DG doses of 200-600 mg/kg, but not
      800 mg/kg, displayed significant cross-correlation, suggesting that large 2DG
      doses may recruit non-specific effects upon food intake. There was no correlation
      between food intake in the absence (vehicle baseline) of and presence of 2DG,
      suggesting that the regulation of glucose intake in non-challenged mice does not
      predict subsequent responses to glucoprivic challenge. The data demonstrate
      genotype-dependent variability in this glucoprivic response, and may provide the
      basis for the subsequent identification of trait-relevant genes.

PMID- 16427101
TI  - Clerodane and labdane diterpenoids from Nuxia sphaerocephala.
AB  - Seven diterpenoids including four clerodane and three labdane derivatives, (13S)
      ent-7beta-hydroxy-3-cleroden-15-oic acid (1), ent-7beta-hydroxy-2-oxo-3-cleroden
      15-oic acid (2), ent-2,7-dioxo-3-clero-den-15-oic acid (3), ent-18-(E)
      caffeoyloxy-7beta-hydroxy-3-cleroden-15-oic acid (4) (13S)-ent-18-(E)
      coumaroyloxy-8(17)-labden-15-oic acid (5), ent-18-(E)-caffeoyloxy-8(17)-labden-15
      oic acid (6), ent-15-(E)-caffeoyloxy-8(17)-labden-18-oic acid (7), have been
      isolated from an ethyl acetate extract of the leaves of Nuxia sphaerocephala,
      together with 17 known compounds. 3-Oxolup-20(29)-en-30-al (3-oxolupenal) (8) and
      3beta-hydroxylup-20(29)-en-30-al (3beta-hydroxy-lupenal) (9) showed the best
      inhibitory activity against Plasmodium falciparum with the IC(50) values between
      1.55 and 4.67 microg/ml in vitro, respectively. The structure and the relative
      stereochemistry of the compounds were established on the basis of their
      spectroscopic properties. The absolute configuration at C-13 of 1 and 5 was
      determined by the PGME amide procedure.

PMID- 16427102
TI  - Surveyed attitudes, perceptions and practices in Norway regarding the use of
      local anaesthesia in piglet castration.
AB  - The last two years piglet castration in Norway has been performed by
      veterinarians and with the use of anaesthesia. In order to evaluate this new
      policy, veterinarians and pig producers were asked to fill out a questionnaire
      regarding their experiences with the new castration practices. The answers showed
      that the piglets were most often castrated using a combination of subcutaneous
      and intratesticular administration of lidocaine with adrenaline at an average age
      of 10 days. The effect of the anaesthesia was regarded as good by 54% of the
      veterinarians and 19% of the producers. Post-operative complications were rare.
      The overall evaluation showed that two-thirds of the veterinarians, but only one
      third of the pig producers were satisfied or very satisfied with the implemented
      policy. However, while two-thirds of the pig producer had a negative attitude to
      the policy before it was implemented, only one-third were dissatisfied after two
      years experience.

PMID- 16427103
TI  - Androgen receptor expression in normal, hyperplastic and neoplastic hepatoid
      glands in the dog.
AB  - Neoplasms of the perianal glands are common in the dog, particularly in the male.
      The occurrence of these tumours appears to be hormone related and castration,
      without excision of the tumour, has sometimes resulted in regression of the
      tumour. The aim of this study was to investigate the expression of androgen
      receptors (AR) in normal, hyperplastic and neoplastic hepatoid glands in the dog.
      Thirty-one samples of canine hepatoid gland tissues were investigated. The
      lesions, classified according to WHO criteria, were comprised of 19 hyperplastic
      tissues, 10 benign lesions (2 hepatoid gland epithelioma and 8 hepatoid
      adenomas), and 19 carcinomas. Five samples from normal hepatoid glands were also
      investigated. The AR expression was evaluated by immunohistochemistry using a
      streptavidin-biotin peroxidase method. The immunoexpression was scored by two
      pathologists as the percentage of positive nuclei. The intensity of staining was
      also considered. AR expression was detected in all normal and abnormal glands.
      However, in hyperplastic tissues the percentage of positive nuclei was
      significantly higher than in normal tissue and especially in reserve basaloid
      cells. A similar increase in the percent of positive nuclei was also observed in
      hepatoid epitheliomas, while in hepatoid adenoma the percent of AR
      immunolabelling was only slightly increased compared to normal tissue. In
      hepatoid carcinomas the percent of AR-positive cells was similar to that observed
      in benign tumours. The grade of differentiation of hepatoid carcinomas did not
      affect AR expression. These results demonstrate that increased AR expression is
      maintained throughout perianal gland cancer progression and that hepatoid gland
      carcinomas still express AR. Although further studies may be required to evaluate
      the hormonal background of these diseases, dogs bearing those carcinomas might
      benefit from castration or anti hormonal therapy.

PMID- 16427104
TI  - Characterization of avian strains of Pasteurella multocida by restriction
      endonuclease and amplified fragment length polymorphism.
AB  - Avian strains of Pasteurella multocida were typed by employing restriction
      endonuclease analysis (REA) and single enzyme-amplified fragment length
      polymorphism (AFLP) to evaluate their applicability for epidemiological studies
      of fowl cholera outbreaks. A total of 72 strains isolated from different avian
      species (chicken, duck, turkey, quail and goose) belonging to various
      geographical regions of India were characterized. REA using two different enzymes
      HhaI and HpaII produced 9 and 18 clusters respectively, whereas Single enzyme
      AFLP recognized 32 patterns out of 72 strains typed. The study indicated that REA
      using HpaII is a simple and resource efficient method, however, further typing
      with more stringent and rapid method like Single enzyme-AFLP, could drastically
      enhance investigation in epidemiological studies of fowl cholera outbreaks.

PMID- 16427105
TI  - Pregnancy impairs ketone body disposal in late gestating ewes: implications for
      onset of pregnancy toxaemia.
AB  - The impact of pregnancy on ketone body disposal during a hyperketonaemic clamp
      was examined by tracer isotope dilution techniques in seven 12 h fasted sheep in
      three reproductive states, in the dry non-gestating period, late in gestation and
      during early lactation. After a sampling period of 60 min under basal conditions
      a DL-BHB racemate solution was continuously infused intravenously for 3 h at
      rates of 14.3-24.3 micromol/(kg min) to elevate the D-BHB concentration in blood
      plasma to values between 5 and 7 mmol/l. Two separate experiments were carried
      out with the same sheep in each of the three reproductive states. During
      pregnancy three ewes were pregnant with a single lamb and four ewes carried
      twins. Maximal D-BHB turnover rates fell significantly in late gestation by 26%
      relative to early lactation and by 22% when compared with the dry non-pregnant
      state. Reduction of maximal D-BHB disposal rate during late gestation was
      accompanied by a significant 297% (p<0.005) and a non-significant 49% increase in
      the basal BHB concentration in blood, a non-significant 10% and 4% decrease in
      the rate constant of D-BHB turnover and a non-significant 24% and 13% rise in the
      incremented increase of D-BHB concentration per unit D-BHB infusion, relative to
      the dry and the lactating period, respectively. Induction of hyperketonaemia
      significantly lowered NEFA and glycerol concentrations in blood by 67% and 57%,
      respectively, compared to the pre-infusional concentrations. The magnitude of
      this effect was the same in all reproductive states and was explained as a direct
      antilipolytic action of D-BHB on adipose tissue. It is concluded that the reduced
      ability of the late gestating ewe to utilize D-BHB promotes hyperketonaemia.
      Since hyperketonaemia exerts several adverse effects, e.g. on energy balance and
      glucose metabolism it appears that the impairment of ketone bodies disposal in
      late pregnancy facilitates development of pregnancy toxaemia, especially in ewes
      carrying twins.

PMID- 16427106
TI  - Evolution of contingent altruism when cooperation is expensive.
AB  - The ubiquity of cooperation has motivated a major research program over the last
      50 years to discover ever more minimal conditions for the evolution of altruism.
      One important line of work is based on favoritism toward those who appear to be
      close relatives. Another important line is based on continuing interactions,
      whether between individuals (e.g., reciprocity) or between lines of descent in a
      viscous population. Here, we use an agent-based model to demonstrate a new
      mechanism that combines both lines of work to show when and how favoritism toward
      apparently similar others can evolve in the first place. The mechanism is the
      joint operation of viscosity and of tags (heritable, observable, and initially
      arbitrary characteristics), which serve as weak and potentially deceptive
      indicators of relatedness. Although tags are insufficient to support cooperation
      alone, we show that this joint mechanism vastly increases the range of
      environments in which contingent altruism can evolve in viscous populations. Even
      though our model is quite simple, the subtle dynamics underlying our results are
      not tractable using formal analytic tools (such as analysis of evolutionarily
      stable strategies), but are amenable to agent-based simulation.

PMID- 16427107
TI  - Uninvadability in N-species frequency models for resident-mutant systems with
      discrete or continuous time.
AB  - The uninvadability concept, that was originally introduced through static
      comparisons of individual fitness in resident-mutant systems for a single
      species, is developed for multi-species models with frequency-dependent fitness
      by extending its equivalent single-species dynamic characterization. This multi
      species definition is then reinterpreted in terms of individual fitness functions
      based on intra and interspecific interactions. The resultant concept is discussed
      in relation to that of an N-species ESS (evolutionarily stable strategy) and to
      dynamic stability of monomorphic and polymorphic evolutionary systems.

PMID- 16427108
TI  - Mutant murine leukemia virus Gag proteins lacking proline at the N-terminus of
      the capsid domain block infectivity in virions containing wild-type Gag.
AB  - We have investigated the properties of murine leukemia virus Gag mutants in which
      the p12-CA cleavage site is altered. In one mutant, the cleavage is blocked; in
      the other, the conserved proline at the N-terminus of CA has been replaced with
      glycine. No infectivity was detected in either mutant. Mutant particles cannot
      synthesize full-length DNA upon infecting permissive cells. Particles composed of
      a mixture of wild-type and mutant proteins have severely impaired infectivity.
      These mixed particles are defective in their ability to synthesize DNA upon
      infection, but this defect is less severe than the loss of infectivity. Thus,
      proteins lacking the correct N-terminus of CA inhibit DNA synthesis and also
      interfere with formation or integration of a full-length, normal provirus. The
      results imply that CA proteins function as part of a large, highly organized
      structure in reverse transcription and apparently at a later step as well.

PMID- 16427109
TI  - Initial destination of the disaccommodation step response.
AB  - Peak velocity and peak acceleration of disaccommodation step responses remain
      invariant of response magnitude for a constant starting position and they
      increase linearly with proximity of starting position. This suggests that
      disaccommodation response is initiated towards an initial (default) destination
      and is switched mid-flight to attain the desired final destination. The dioptric
      location of initial destination was estimated from the x-intercept of regression
      of peak velocity on response starting position. The x-intercept correlated well
      with subject's cycloplegic refractive state and poorly with their dark focus of
      accommodation. Altering the dark focus by inducing fatigue in the accommodative
      system did not alter the x-intercept. These observations suggest that cycloplegic
      refractive state is a good behavioral correlate of initial destination of
      disaccommodation step responses.

PMID- 16427110
TI  - Lightness constancy in 4-month-old infants.
AB  - In the present study, discrete trial familiarization/novelty techniques were used
      to study lightness constancy in 4-month-old infants. The test stimuli were real
      objects (paper smiley faces) of two different reflectances, dark gray (17%
      reflectance) and light gray (54% reflectance). In Experiment 1, the test stimuli
      were viewed against a white (90% reflectance) surround, and in Experiment 2,
      against a black (4.6% reflectance) surround. In Experiments 1 and 2, the
      illumination was changed between familiarization and test phases of each trial.
      In Experiment 3, the reflectance of the surround was changed from white to mid
      gray (28.5% reflectance) between familiarization and test phases of each trial.
      With the white surround, the infants preferred the face with the novel
      reflectance, consistent with the presence of lightness constancy. With the black
      surround, the infants showed no preference between faces with novel reflectance
      vs. novel luminance. With the changing surround, the infants showed a small
      preference for the stimulus with the novel ratio, as opposed to the stimulus with
      the novel reflectance and the novel luminance. The results are discussed in the
      context of adult cues for lightness constancy, including white anchor points and
      local luminance ratios.

PMID- 16427111
TI  - Bacterial degradation of microcystin toxins within a biologically active sand
      filter.
AB  - Microcystin toxins are a problem for water authorities as they are recalcitrant
      to conventional water treatment. In this study, biological sand filtration was
      assessed in laboratory column experiments for its ability to remove two
      microcystin analogues, microcystin-LR and microcystin-LA. A lag period of 3 days
      was evident prior to the commencement of degradation. Contact times were varied
      during the experiment; however, no microcystin was detected in the effluent after
      4 days, even under conditions similar to those of a rapid sand filter. Removals
      of microcystin through the sand filters were shown to be primarily through
      biological degradation processes. Using polymerase chain reaction (PCR), biofilm,
      extracted from one of the sand filters that had effectively removed the
      microcystins, was shown to contain bacteria with the mlrA gene. Detection of this
      gene provided additional evidence that biological degradation of microcystin was
      the primary removal mechanism.

PMID- 16427112
TI  - Occurrence of methanogenesis during start-up of a full-scale synthesis gas-fed
      reactor treating sulfate and metal-rich wastewater.
AB  - The start-up of a full-scale synthesis gas-fed gas-lift reactor treating metal
      and sulfate-rich wastewater was investigated. Sludge from a pilot-scale reactor
      was used to seed the full-scale reactor. The main difference in design between
      the pilot- and full-scale reactor was that metal precipitation and sulfate
      reduction occurred in the same reactor. After 7 weeks the full-scale reactor
      achieved the sulfate conversion design rate of 15 kg/m3day. Zinc sulfide
      precipitation inside the reactor did not interfere with obtaining a high rate of
      sulfate reduction. 16S rRNA gene analysis demonstrated that the bacterial
      communities in both reactors were dominated by the sulfate-reducing genus
      Desulfomicrobium. Archaeal communities of both reactors were dominated by the
      methanogenic genus Methanobacterium. Most Probable Number (MPN) counts confirmed
      that heterotrophic Sulfate-Reducing Bacteria (SRB) were dominant (10(11) -10(12)
      cells/g VSS) compared to homoacetogens (10(5) -10(6) cells/g VSS) and methanogens
      (10(8) -10(9) cells/g VSS). Methanogenesis was not suppressed during start-up of
      the full scale-reactor, despite the predominance of SRB, which have a lower
      hydrogen threshold. Due to the short sludge retention time (4-7 days) competition
      for hydrogen is determined by Monod kinetics, not hydrogen thresholds. As the
      kinetic parameters for SRB and methanogens are similar, methanogenesis may
      persist which results in a loss of hydrogen.

PMID- 16427113
TI  - Biological hydrogen production by Clostridium acetobutylicum in an unsaturated
      flow reactor.
AB  - A mesophilic unsaturated flow (trickle bed) reactor was designed and tested for
      H2 production via fermentation of glucose. The reactor consisted of a column
      packed with glass beads and inoculated with a pure culture (Clostridium
      acetobutylicum ATCC 824). A defined medium containing glucose was fed at a flow
      rate of 1.6 mL/min (0.096 L/h) into the capped reactor, producing a hydraulic
      retention time of 2.1 min. Gas-phase H2 concentrations were constant, averaging
      74 +/- 3% for all conditions tested. H2 production rates increased from 89 to 220
      mL/hL of reactor when influent glucose concentrations were varied from 1.0 to
      10.5 g/L. Specific H2 production rate ranged from 680 to 1270 mL/g glucose per
      liter of reactor (total volume). The H2 yield was 15-27%, based on a theoretical
      limit by fermentation of 4 moles of H2 from 1 mole of glucose. The major
      fermentation by-products in the liquid effluent were acetate and butyrate. The
      reactor rapidly (within 60-72 h) became clogged with biomass, requiring manual
      cleaning of the system. In order to make long-term operation of the reactor
      feasible, biofilm accumulation in the reactor will need to be controlled through
      some process such as backwashing. These tests using an unsaturated flow reactor
      demonstrate the feasibility of the process to produce high H2 gas concentrations
      in a trickle-bed type of reactor. A likely application of this reactor technology
      could be H2 gas recovery from pre-treatment of high carbohydrate-containing
      wastewaters.

PMID- 16427115
TI  - Effect of chemical and physical parameters on a pulp mill biotreatment bacterial
      community.
AB  - The bacterial community composition in an activated sludge plant treatment from a
      bleached kraft pulp mill was monitored over a period of 209 days. Using DGGE and
      terminal-Restriction Fragment Length Polymorphism (t-RFLP) analysis we generated
      community DNA fingerprints over the time period. Both methods produce
      fingerprints that can be used to monitor stability in the system and generate
      fragments that can be associated with bacterial taxa. Chemical and physical
      parameters were also collected during that same time frame. We found a number of
      significant correlations with influent variables such as temperature, chemical
      oxygen demand (COD), Biochemical oxygen demand (BOD) and chloroform
      concentrations suggesting that these were the most likely parameters to influence
      the bacterial community structure. In addition several taxa correlated to
      important performance indicators such as COD/BOD removals and SVI. Multivariate
      analysis also confirmed the strong links between taxa variation and temperature,
      nutrient loads, chloroform and also one class of filaments. Establishing the
      identity of these taxa and their ecological preferences will greatly enhance our
      understanding and management of biological treatment systems.

PMID- 16427114
TI  - Effects of operational parameters on cake formation of CaSO4 in nanofiltration.
AB  - Inorganic fouling is one of the major limitations of nanofiltration (NF)
      application in drinking water treatment. In this study, we report the effect of
      operating parameters on the fouling of NF membranes by CaSO4 in terms of cake
      growth at membrane surface under various operating conditions. Increasing
      operating pressure and decreasing crossflow velocity promote CaSO4 nucleation and
      crystallization, thus enhance membrane fouling. The flux decline and its dynamics
      due to the change of operating parameters are assessed quantitatively based on a
      resistance model. Applied filtration pressure is found to have the most dominant
      impact on the inorganic fouling. It is shown that the filtration resistance
      caused by the formation and growth of CaSO4 cake on membrane surface is dependent
      on operating parameters.

PMID- 16427116
TI  - Removal of 1,4-dioxane from water using sonication: effect of adding oxidants on
      the degradation kinetics.
AB  - This research investigates the effect of adding oxidants such as Fe0, Fe2+ and
      S2O8(2-) in the sonication of 1,4-dioxane (1,4-D). The results indicate that the
      degradation pattern of 1,4-D kinetically could be divided into three steps
      (initiation, acceleration, and stabilization), with the first two steps
      predominating. The initiation step agreed with zero order rate model, while the
      acceleration step was the pseudo-first order. In the presence of HCO3- as a
      radical scavenger, the degradations of 1,4-D and TOC were suppressed, indicating
      that OH radical is an important factor in the sonolysis, especially at the
      acceleration step. The overall degradation efficiency of 79.0% in the sonolysis
      of 1,4-D was achieved within 200 min. While Fe0, Fe2+ and S2O8(2-) were
      individually combined with sonication, the total degradation efficiency of 1,4-D
      increased 18.6%, 19.1% and 16.5% after 200 min, respectively. The addition of
      oxidants not only increased the rate constant in the acceleration step, but also
      changed the kinetic model from zero to pseudo-first order at the initiation step.
      The addition of oxidants such as Fe2+, Fe0 and S2O8(2-) in the sonication of 1,4
      D also improved the mineralization of 1,4-D. However, the degradation
      efficiencies of 1,4-D and TOC were not statistically different (p = 0.709, ANOVA)
      with different oxidants such as Fe2+, Fe0 and S2O8(2-).

PMID- 16427117
TI  - Long-term changes in pollutant load outflows and purification function in a paddy
      field watershed using a circular irrigation system.
AB  - A long-term investigation on the water quality and hydrology was carried out for
      8 years and 7 months (from October 1991 to April 2000) in a paddy field watershed
      using a circular irrigation system. The annual amount of rainfall ranged from
      1270 to 2226 mm and it was found that the amount of irrigation water tended to
      decrease as rainfall increased. Phosphorus and chemical oxygen demand (COD)
      concentrations tended to decrease with the river flowing down, whereas nitrogen
      concentrations showed no significant difference. The annual outflow loads (sum of
      the net-outflow load during irrigation periods and the outflow load during non
      irrigation periods) of total nitrogen (T-N), total phosphorus (T-P), and COD
      ranged from 13.6 to 75.3 kg ha(-1)yr(-1), -3.55 to 2.21 kg ha(-1)yr(-1), and 
      24.7 to 48.5 kg ha(-1)yr(-1), respectively. The negative values for T-P and COD
      loads indicated that the study watershed performed a purification function. The
      change in annual pollutant loads was primarily attributed to the amount of
      hydrological water volumes (the annual amount of rainfall or that of rainfall
      plus irrigation water) for T-N and COD loads and partially for T-P load. In
      addition, the purification function was related to the hydraulic retention time,
      and the study watershed allows sufficient retention for pollutant purification
      for phosphorus and COD contents and partially for nitrogen content.

PMID- 16427118
TI  - Comparative effectiveness of solar disinfection using small-scale batch reactors
      with reflective, absorptive and transmissive rear surfaces.
AB  - This study investigated the enhancement of solar disinfection using custom-made
      batch reactors with reflective (foil-backed) or absorptive (black-backed) rear
      surfaces, under a range of weather conditions in India. Plate counts of
      Escherichia coli ATCC11775 were made under aerobic conditions and under
      conditions where reactive oxygen species (ROS) were neutralised, i.e. in growth
      medium supplemented with 0.05% w/v sodium pyruvate plus incubation under
      anaerobic conditions. While the addition of either an absorptive or a reflective
      backing enhanced reactor performance under strong sunlight, the reflective
      reactor was the only system to show consistent enhancement under low sunlight,
      where the process was slowest. Counts performed under ROS-neutralised conditions
      were slightly higher than those in air, indicating that a fraction of the cells
      become sub-lethally injured during exposure to sunlight to the extent that they
      were unable to grow aerobically. However, the influence of this phenomenon on the
      dynamics of inactivation was relatively small.

PMID- 16427119
TI  - Treatment of naphthalene-2-sulfonic acid from tannery wastewater by a granular
      activated carbon fixed bed inoculated with bacterial isolates Arthrobacter
      globiformis and Comamonas testosteroni.
AB  - The kinetics of naphthalene-2-sulfonic acid (2-NSA) adsorption by granular
      activated carbon (GAC) were measured and the relationships between adsorption,
      desorption, bioavailability and biodegradation assessed. The conventional
      Langmuir model fitted the experimental sorption isotherm data and introduced 2
      NSA degrading bacteria, established on the surface of the GAC, did not interfere
      with adsorption. The potential value of GAC as a microbial support in the aerobic
      degradation of 2-NSA by Arthrobacter globiformis and Comamonas testosteroni was
      investigated. Using both virgin and microbially colonised GAC, adsorption removed
      2-NSA from the liquid phase up to its saturation capacity of 140 mg/g GAC within
      48 h. However, between 83.2% and 93.3% of the adsorbed 2-NSA was bioavailable to
      both bacterial species as a source of carbon for growth. In comparison to the non
      inoculated GAC, the combination of rapid adsorption and biodegradation increased
      the amount (by 70-93%) of 2-NSA removal from the influent phase as well as the
      bed-life of the GAC (from 40 to >120 d). A microbially conditioned GAC fixed-bed
      reactor containing 15 g GAC removed 100% 2-NSA (100 mg/l) from tannery wastewater
      at an empty bed contact time of 22 min for a minimum of 120 d without the need
      for GAC reconditioning or replacement. This suggests that small volume GAC
      bioreactors could be used for tannery wastewater recycling.

PMID- 16427120
TI  - Prognostic value of canine frozen-thawed semen parameters on in vitro sperm
      oocyte interactions.
AB  - Combining the data from conventional semen analysis with oocyte penetration
      assays should improve the assessment of the fertilizing ability of a semen
      sample. Thus, the objective of the present study was to evaluate the prognostic
      value of various semen parameters on the in vitro interactions between frozen
      thawed canine sperm and homologous oocytes. Ten ejaculates from five stud dogs
      (two ejaculates/dog) were collected by digital manipulation. Semen samples were
      evaluated, extended in Tris-egg yolk-glycerol, frozen and stored in liquid
      nitrogen, and thawed several weeks later. Samples were evaluated for motility and
      sperm populations by computer-aided semen analysis (CASA), plasma membrane
      integrity (carboxy-fluorescein diacetate and propidium iodide), and sperm
      morphology (Bengal Rose). Thawed spermatozoa were also incubated with homologous
      oocytes for 18 h in an atmosphere of 5% CO(2) and 95% air at 38 degrees C and
      sperm-oocyte interactions were evaluated. Simple linear regression models were
      calculated, with sperm parameters as independent variables and sperm-oocyte
      interactions as the dependent variable. There were significant associations
      between: percentage of oocytes bound to spermatozoa and beat cross frequency
      (BCF; R(2)=63%); percentage of oocytes that interacted with spermatozoa and BCF
      (R(2)=73%); and number of penetrated spermatozoa and velocity average pathway
      (VAP; R(2)=64%) and velocity straight line (VSL; R(2)=64%). Although plasma
      membrane integrity and sperm morphology had little prognostic value for in vitro
      interactions between canine frozen-thawed sperm and homologous oocytes, some
      motility patterns (evaluated by CASA) were predictive of in vitro sperm-oocyte
      interactions.

PMID- 16427121
TI  - Influence of radiant exposure on contraction stress, degree of conversion and
      mechanical properties of resin composites.
AB  - OBJECTIVE: To verify the influence of radiant exposure (H) on contraction stress
      (CS), degree of conversion (DC) and mechanical properties of two restorative
      composites. METHODS: Filtek Z250 (3M ESPE) and Heliomolar (Ivoclar) were
      photoactivated with 6, 12, 24, or 36 J/cm2 at continuous irradiance of 600
      mW/cm2. CS at 10 min was determined in a low compliance testing system. DC,
      flexural strength (FS), flexural modulus (FM) and Knoop microhardness (KHN) were
      measured after 24 h storage at 37 degrees C. KHN and DC measurements were
      conducted on the irradiated surface of 1mm thick disk-shaped specimens. Bar
      shaped specimens were submitted to three-point bending to determine FS and FM.
      Data were analyzed by one-way ANOVA/Tukey's test (alpha = 0.05) separately for
      each composite. RESULTS: For Filtek Z250, no significant increase in CS was
      observed above 12 J/cm2. DC and FM were similar at all H values, while FS
      increased significantly between 6 and 24 J/cm2. KHN was significantly different
      among all H levels, except between 12 and 24 J/cm2. For Heliomolar, CS and KHN
      increased significantly with H, except between 24 and 36 J/cm2. DC, FM and FS did
      not vary, regardless of the radiant exposure. SIGNIFICANCE: Variables tested
      behaved differently. CS and KHN were more sensitive to increasing radiant
      exposures than the other properties evaluated. FS varied only for Filtek Z250,
      while, for both composites, DC and FM were not affected by different H values.

PMID- 16427122
TI  - The effect of silane on the bond strengths of fiber posts.
AB  - OBJECTIVES: Esthetic posts have been developed to maximize the foundation of
      esthetic restorations. The purpose of this study was to evaluate the effect of
      silane on the bond strength of three fiber-reinforced resin posts (fiber posts).
      METHODS: Fifty-four extracted human maxillary central incisors and canines were
      endodontically treated. D.T. Light Post (DT, Bisco), FRC Postec (FR, Ivoclar
      Vivadent), and ParaPost Fiber White (PP, Coltene/Whaledent) were inserted using
      the resin adhesive system provided by the respective manufacturer. For half of
      the specimens in each group, the fiber posts were treated with a silane solution
      (Monobond S, Ivoclar Vivadent). A push-out test was performed on three different
      sections of each root to measure bond strengths. Data were analyzed with ANOVA
      and Bonferroni's post hoc test at P<0.05. RESULTS: The use of silane did not
      result in any statistically significant difference at any level of the root.
      Silane did not result in any significant different bond strengths (MPa) for each
      of the posts. When the data were pooled, the use of silane did not result in
      statistically significant different bond strengths at P>0.403: No silane=12.7+/
      8.4; Silane=14.1+/-7.0. The coronal third of the root (17.5+/-6.7) resulted in
      statistically greater bond strengths than the medium third (12.9+/-6.8) and than
      the apical third (9.8+/-7.3) at P<0.002 and P<0.0001, respectively. The medium
      third and the apical third resulted in no statistically significant different
      bond strengths from each other at P>0.07. The type of post did not result in
      statistically significant different bond strengths at P>0.417: DT=14.7+/-6.8 MPa;
      FR=13.3+/-6.6 MPa; PP=12.2+/-6.6 MPa. SIGNIFICANCE: The use of a silane coupling
      agent did not increase the push-out bond strengths of the three fiber posts used
      in this study. All posts bonded to root dentin at the same magnitude. Bonding is
      more predictable at the most coronal level of the root.

PMID- 16427123
TI  - The effect of calcium hydroxide on solubilisation of bio-active dentine matrix
      components.
AB  - Calcium hydroxide (Ca(OH)(2)) has been used extensively to induce dentine
      regeneration through formation of dentine bridges at sites of pulp exposure after
      dental tissue injury, however, the biological processes underpinning these events
      are unclear. We hypothesise that growth factors and other bio-active molecules,
      sequestered within dentine matrix, may be released by the action of Ca(OH)(2) and
      signal gene expression in pulp cells, which mediates the changes in cell
      behaviour observed during regeneration. Powdered sound, human dentine samples
      were extracted with either 0.02 m Ca(OH)(2), pH 11.7 or 10% EDTA, pH 7.2 ( a
      control known extractant of bio-active and other ECM molecules from dentine) over
      a 14-day period. Extracts were compared for non-collagenous protein (NCP) and
      glycosaminoglycan (GAG) content using dye binding assays and protein compositions
      were analysed by 1D-polyacrylamide gel electrophoresis (1D-PAGE) and TGF-beta1
      ELISA. The effects of extracts on TGF-beta1, Collagen-1alpha and Nestin gene
      expression were analysed using semi-quantitative RT-PCR in the dental MDPC-23, OD
      21 and fibroblastic Swiss 3T3 cell lines following 24h of exposure. Ca(OH)(2)
      solubilised NCPs and GAGs from the dentine ECM, although with a lower yield than
      the EDTA solution and with different kinetics. 1D-PAGE analysis demonstrated some
      differences in profiles for proteins solubilised from dentine by Ca(OH)(2) and
      EDTA. Both solutions released TGF-beta1 from the dentine with higher
      concentrations present in the EDTA (1.395 +/- 0.036 ng/mg) versus the Ca(OH)(2)
      (0.364 +/- 0.012 ng/mg) extract. Notably, both extracts induced similar gene
      expression profiles in all cell lines. These data provide a rational explanation
      for the action of Ca(OH)(2) during pulp capping in which the cellular activities
      involved in dentine bridge formation may be mediated through release of growth
      factors and other bio-active molecules from the dentine by Ca(OH)(2).

PMID- 16427124
TI  - Quantitative kinetic analysis of gene expression during human osteoblastic
      adhesion on orthopaedic materials.
AB  - Little information was found in the literature about the expression on
      hydroxyapatite (HA) materials of genes specific of cellular adhesion molecules
      although more were found on titanium-based substrates. Hence, the goal of this
      work was to study by a kinetic approach from 30 min to 4 days the adhesion of
      Saos-2 cells on microporous (mHA) and non-microporous hydroxyapatite (pHA) in
      comparison to polished titanium. Our strategy associated the visualization of
      adhesion proteins inside the cells by immunohistochemistry and the quantitative
      expression of genes at mRNA level by real-time PCR. The cell morphology was
      assessed using scanning electron microscopy and the number of cells thanks to
      biochemical techniques. The cellular attachment was the highest on mHA from 30
      min to 24 h although the cell growth on mHA was the lowest after 4 days.
      Generally, the Saos-2 osteoblastic cells morphology on mHA was radically
      different than on other surfaces with the particularity of the cytoplasmic edge,
      which appeared un-distinguishable from the surface. The revelation by specific
      antibodies of proteins of the cytoskeleton (actin) and the focal adhesions (FAK,
      phosphotyrosine) confirmed that adhesion and spreading were different on the 3
      materials. The actin stress fibres were less numerous and shorter on mHA
      ceramics. Cells had more focal contacts after 4 h on mHA compared to other
      substrates but less after 24 h. The highest values of total proteins were
      extracted from mHA at 0.5 and 24 h and from pHA at 1, 4, and 96 h. The alphav and
      beta1 integrin, actin, FAK, and ERK gene expression were found to be different
      with adhesion time and with materials. C-jun expression was comparable on mHA,
      titanium and plastic but was largely higher than on pHA at 0.5 and 1 h. On the
      contrary, c-fos expression was the highest on pHA after 0.5 h and the lowest
      after 1h. This difference between c-fos and c-jun expression on pHA after 0.5 h
      could be related to the fact that these two genes may differ in their signalling
      pathways. The expression of the alkaline phosphatase gene after 4 days was lower
      on mHA compared to other materials demonstrating that the microstructure of the
      mHA ceramic was not favourable to Saos-2 cells differentiation. Finally, it was
      demonstrated in this study that HA and titanium surfaces influence as well gene
      expression at early times of adhesion as the synthesis of adhesion proteins but
      also proliferation and differentiation phases. Indeed, the signal transduction
      pathways involved in adhesion of Saos-2 cells on HA and titanium were confirmed
      by the sequential expression of alphav and beta1 integrins, FAK, and ERK genes
      followed by the expression of c-jun and c-fos genes for proliferation and
      alkaline phosphatase gene for differentiation.

PMID- 16427125
TI  - Apoptosis induction by Epican Forte in HTLV-1 positive and negative malignant T
      cells.
AB  - The effects of a novel nutrient formulation Epican Forte (EF) were evaluated on
      proliferation and induction of apoptosis using non-cytotoxic concentrations
      against HTLV-1 positive (HuT-102 & C91-PL) and negative (CEM & Jurkat) cells. EF
      showed anti-proliferative effect as determined by MTT assay and TGF mRNA protein
      expression using RT-PCR. EF resulted in the down-regulation of TGF-alpha and an
      up-regulation in TGF-beta2. EF caused a significant increase in apoptotic cells
      in the preG1 phase. These results were confirmed using Cell Death ELISA and
      Annexin V-FITC. Induction of apoptosis was caused by an up-regulation of p53, p21
      and Bax protein levels and a down-regulation of Bcl-2alpha protein expression
      level.

PMID- 16427126
TI  - Differential reactive oxygen and nitrogen production and clearance of Salmonella
      serovars by chicken and mouse macrophages.
AB  - The objective of the present study was to compare the uptake and killing of
      Salmonella serovars by murine and avian macrophage cell lines. We used Salmonella
      enterica serovars Enteritidis (SE338) and Typhimurium (SR11) for this study.
      Uptake of green fluorescent protein-labeled bacteria was measured using flow
      cytometry. Cell sorting and plating of viable infected macrophages demonstrated
      that bacterial clearance was significantly better with J774A.1 compared with HD11
      cells. HD11 cells produced significantly higher amounts of nitric oxide (NO) than
      J774A.1 cells upon infection with SE338 and SR11, whereas J774A.1 cells exhibited
      greater superoxide production with SR11. Treatment of HD11 cells with recombinant
      chicken interferon gamma in the absence of bacteria enhanced NO production but
      did not induce increased levels synergistically with bacteria. Interferon
      treatment did not influence phagocytosis or increase killing by HD11 cells.

PMID- 16427127
TI  - Ethanol modulation of GABAergic transmission: the view from the slice.
AB  - For almost three decades now, the GABAergic synapse has been the focus of intense
      study for its putative role in mediating many of the behavioral consequences
      associated with acute and chronic ethanol exposure. Although it was initially
      thought that ethanol interacted solely with the postsynaptic GABAA receptors that
      mediate the majority of fast synaptic inhibition in the mammalian central nervous
      system (CNS), a number of recent studies have identified novel pre- and
      postsynaptic mechanisms that may contribute to the acute and long-term effects of
      ethanol on GABAergic synaptic inhibition. These mechanisms appear to differ in a
      brain region specific manner and may also be influenced by a variety of
      endogenous neuromodulatory factors. This article provides a focused review of
      recent evidence, primarily from in vitro brain slice electrophysiological
      studies, that offers new insight into the mechanisms through which acute and
      chronic ethanol exposures modulate the activity of GABAergic synapses. The
      implications of these new mechanistic insights to our understanding of the
      behavioral and cognitive effects of ethanol are also discussed.

PMID- 16427128
TI  - Emotional task-dependent low-frequency fluctuations and methylphenidate: Wavelet
      scaling analysis of 1/f-type fluctuations in fMRI of the cerebellar vermis.
AB  - Ion channel currents, neural firing patterns, and brain BOLD signals display 1/f
      type fluctuations or fractal properties in time. By design, fMRI methods attempt
      to minimize the contribution of variance from low-frequency physiological 1/f
      noise. New fMRI methods are described to visualize and measure 1/f-type BOLD
      fluctuations in volunteers recalling affectively neutral or emotional memories or
      meditating (i.e., attending to breathing) then retrospectively rating emotional
      content. A wavelet scaling exponent (alpha) was used to characterize signals from
      0.015625 to 0.5Hz in cerebellar lobules VIII to X of the vermis (posterior
      inferior vermis; PIV), a region coordinating balance, eye tracking, locomotion,
      and vascular tone, and a possible site of pathology in attention deficit
      hyperactivity disorder (ADHD). RESULTS: Changes in alpha and emotional measures
      were correlated in PIV voxels (r = 0.622, d.f .= 14, P < 0.0005), but not other
      regions examined. In contrast, conventional means and standard deviations of PIV
      voxels were unchanged. Methylphenidate, shown to decrease slow oscillations in
      rodent basal ganglia [Ruskin DN, Bergstrom DA, Shenker A, Freeman LE, Baek D,
      Walters JR. Drugs used in the treatment of attention-deficit/hyperactivity
      disorder affect postsynaptic firing rate and oscillation without preferential
      dopamine autoreceptor action. Biol Psychiatry 2001;49:340-50.], abolished task
      dependent alpha changes in the PIV of an adult with ADHD. Wavelet analysis of
      long BOLD time series appears well suited to fractal physiology and studies of
      pharmacologically modulated cerebellar-thalamic-cortical function in ADHD or
      other psychiatric disorders.

PMID- 16427129
TI  - The relationship of working memory, inhibition, and response variability in child
      psychopathology.
AB  - INTRODUCTION: The aim of this study was to investigate the relationship between
      working memory and inhibition in children with attention deficit hyperactivity
      disorder (ADHD), high-functioning autism (HFA), and Tourette syndrome (TS),
      compared to normally developing children. Furthermore, the contribution of
      variation in processing speed on working memory and inhibition was investigated
      in these childhood psychopathologies. METHOD: Four groups of children are
      reported in this study: 65 children with ADHD, 66 children with HFA, 24 children
      with TS, and 82 normal control children. All children were in the age range of 6
      13 years. RESULTS: The relationship between working memory and inhibition was
      similar in children with ADHD, HFA, TS, and normally developing children. The
      relationship between both domains did not alter significantly for any of the
      groups, when variation in processing speed was taken into account. More symptoms
      of hyperactivity/impulsivity are related to a poorer inhibitory process and
      greater response variability. More symptoms of autism are related to a poorer
      working memory process. CONCLUSION: The current study showed that working memory,
      inhibition, and response variability, are distinct, but related cognitive domains
      in children with developmental psychopathologies. Research with experimental
      manipulations is needed to tackle the exact relationship between these cognitive
      domains.

PMID- 16427130
TI  - Towards a neuroscience of attention-deficit/hyperactivity disorder: fractionating
      the phenotype.

PMID- 16427131
TI  - Biphasic course in bipolar II outpatients: prevalence and clinical correlates of
      a cyclic pattern described by Baillarger and Falret in hospitalised patients in
      1854.
AB  - BACKGROUND: Biphasic course refers to a mood episode immediately followed by one
      of opposite polarity and then usually by a free interval. It was described under
      the rubric of folie a double forme among psychiatric inpatients by the French
      psychiatrist Baillarger 150 years ago. A rapid cycling form (folie circulaire)
      was also described in the same year by his compatriot Falret. These patients
      would probably have today met the criteria for bipolar I. Our aim was to find the
      prevalence and clinical correlates of biphasic course in bipolar II (BP II) in
      contemporary ambulatory patients. METHODS: Consecutive 206 BP II outpatients were
      interviewed in the first author's private practice, using a modified Structured
      Clinical Interview for DSM-IV. To assign a patient to biphasic episode, it must
      have occurred at least once when not on an antidepressant. RESULTS: Frequency of
      biphasic course was 80%. Biphasic vs. non-biphasic course was significantly
      higher in polyepisodic major depressive episode (MDE) and those with
      antidepressant-associated hypomania; the same was true for index melancholic
      subtype, where index of Global Assessment of Functioning scale (GAF) score was
      lower. Female gender, age at onset, mixed depressive episodes and bipolar family
      history were not significantly different between the two groups. LIMITATIONS:
      Patients were not observed on a prospective basis. We cannot report on the
      relative proportion of MDE preceded vs. followed by hypomania, because such
      distinction was not part of FB's naturalistic database. CONCLUSIONS: Strikingly
      in line with Baillarger's observation 150 years ago, biphasic course represented
      the typical pattern in this outpatient private practice sample of BP II. That
      antidepressant-associated hypomania was significantly more common in the biphasic
      course variety suggests that when MDE preceded hypomania-in such patients,
      antidepressants might have simply accentuated the natural cycle rather than
      causing it. Switching in the clinical setting then seems to depend on a biphasic
      cyclic baseline aggravated by antidepressant use. The fact that mixed states were
      equally prevalent in both course patterns suggests that the mechanisms involved
      in switching and mixity may be distinct. The significantly higher number of
      melancholic episodes with lower GAF scores indicates that-in line with Falret's
      description-overall, the biphasic course represents a relatively unfavorable
      outcome pattern.

PMID- 16427133
TI  - Core transference themes in depression.
AB  - BACKGROUND: Psychodynamic and psychoanalytic theories assume that depression is
      concomitant with typical transference patterns. We tested whether depression can
      indeed be understood in these terms, and determined a parsimonious set of
      transference themes that are most typical of depression. METHOD: Transference
      patterns were assessed with the Core Conflictual Relationship Theme (CCRT)
      method, which examines transference patterns (wishes, responses of the other, and
      responses of the self), and which was applied to clinical interview data from
      mental health outpatients. Depression was assessed with the Beck Depression
      Inventory-II. Data were analyzed by means of the leaps and bounds regression
      algorithm and bootstrapping. RESULTS: Depression can significantly be explained
      by typical wishes, typical subjective perceptions of how the other responds, and
      typical responses of the self to the other. We mapped a set of four transference
      themes that are most representative of depression: (1) a strong wish to feel
      happy guides interactions, (2) the perception that others dislike one is typical,
      (3) one's own reactions of disliking others are apparent, and (4) one experiences
      feelings of helplessness. LIMITATIONS: No control group was used. The limited
      amount of research in the field and the various methodological approaches in
      different studies make it difficult to compare our findings. CONCLUSION: Linking
      depression to transference patterns is valid. The set of transference themes that
      were selected cohere in a meaningful way. These themes can be expected when
      clinically treating depressed patients.

PMID- 16427132
TI  - The detection of depression in medical setting: a study with PRIME-MD.
AB  - BACKGROUND: Studies investigating the performance of instruments to detect major
      depressive disorder (MDD) have reported inconsistent results. Subsyndromal
      depression (SD) has also been associated to increased morbidity, and little is
      known about its detection in primary care setting. This study aimed to
      investigate the performance of the Primary Care Evaluation of Mental Disorders
      (PRIME-MD) to detect MDD and any depression (threshold at SD) in an outpatient
      unit of a teaching general hospital. METHODS: Nineteen primary care physicians
      using the PRIME-MD evaluated 577 patients, 240 of them (75% female; mean age,
      40.0 +/- 14.4), including all with MDD and a randomly subset of those without
      MDD, were evaluated by 11 psychiatrists using the Structured Clinical Interview
      Axis I Disorders, Patient Version (SCIDI/P) for DSM-IV as the standard
      instrument. RESULTS: The kappa between the PRIME-MD and the SCID was 0.42 for the
      diagnosis of any depression and 0.32 for MDD. The distribution of the number of
      depressive symptoms per patient suggested the existence of a continuum between SD
      and MDD, and a high frequency of subjects with 4-6 symptoms (close to the cutoff
      for the diagnosis of MDD). LIMITATIONS: The sample has a modest size and is a
      subset of an original one. CONCLUSION: A continuum between SD and MDD may in part
      explain the relatively low agreement for the diagnosis of MDD in our sample and
      possibly in other studies. Studies investigating the performance of screening
      instruments to detect MDD, should consider the relevance of identifying SD, and
      the influence of the distribution of the number of depressive symptoms in their
      results.

PMID- 16427135
TI  - Cyclothymia and labile personality: is all folie circulaire?
AB  - BACKGROUND: Historically, cyclothymia has been used broadly to refer either to a
      temperament (Kretschmer) or the entire range of bipolar disorders. Within this
      spectrum, it is uncertain whether it characterizes the "hard" (or manic
      depressive) forms (as Kurt Schneider argued) or its "soft" expressions (bipolar
      II and highly recurrent depressions); the latter perspective is in line with
      Falret's view that the melancholic expressions of his folie circulaire (circular
      insanity) were highly prevalent in the community. METHODS: Eight hundred forty
      three outpatients were interviewed with the Schedule for Affective Disorders and
      Schizophrenia without regard to hierarchical exclusionary rules. RESULTS:
      Compared to 630 psychiatrically interviewed outpatients who did not have
      cyclothymia, 163 cyclothymics were significantly more likely to have most of the
      disorders listed in the SADS in univariate analyses. Discriminant analyses
      limited the significant associations to labile personality, bipolar II,
      intermittent depression, secondary depression, hypomanic disorder and
      schizoaffective mania. LIMITATION: The RDC construct of cyclothymia is rather
      broad. CONCLUSIONS: Despite such operational breadth, cyclothymia was nonetheless
      largely limited to the soft end of the bipolar spectrum where labile moods and
      depressive recurrence predominate. In this sense, it is natural to place it on
      the border of manic-depressive psychosis. Although Kurt Schneider was the first
      to describe the "labile psychopath" [personality], he believed it was unrelated
      to his narrow concept of cyclothymia, which he used synonymously with manic
      depressive psychosis. Our data do not support his position. Instead, they support
      both Kretchmer's and Falret's views.

PMID- 16427134
TI  - The mood-instability hypothesis in the origin of mood-congruent versus mood
      incongruent psychotic distinction in mania: validation in a French National Study
      of 1090 patients.
AB  - BACKGROUND: Although included in successive editions of the DSM since its
      introduction in the IIIrd, the subtyping of manic episode into 'with mood
      congruent (MCP) versus mood-incongruent (MIP) psychotic features' is yet to be
      fully validated. METHODS: One thousand and ninety consecutive manic patients were
      recruited at 19 medical centers in France from December 2000 to April 2002.
      Patients were systematically assessed for sociodemographic characteristics,
      illness course, phenomenology and had to fill out biphasic mood charts during the
      first study week. RESULTS: Five hundred forty-four manic patients were psychotic,
      364 (33.4%) being MCP, 180 (16.5%) MIP. Although both groups scored high on the
      Mania Rating Scale, MIP patients had significantly more often been diagnosed as
      schizophrenic, or anxiety disorders, with long delays to first diagnosis as
      bipolar disorder. MIP were also significantly different in a variety of domains:
      2:1 female/male ratio; shorter free intervals between episodes; more auditory
      hallucinations, reference, persecutory and somatic delusions; more stressors;
      more anger; higher depression scores and diurnal variation of mood, as well as
      anxious symptoms and hyperemotionality upon improvement. CONCLUSIONS: MCP and MIP
      manias occurred in nearly half of this largest sample of manic patients ever
      reported. As postulated 150 years ago by Falret and Baillarger in France, free
      intervals, characterize both forms of circular insanity. Both are prevalent and
      severe remitting forms of mania, but the latter differs from the former by much
      shorter free intervals, greater instability of mood and mixed anxious-depressive
      features. This is compatible with the Vienna School hypothesis that dysphoric
      instability of the patient may induce emotional reactions in significant others,
      which, in turn, might lead to extremely paranoid and psychotic symptom formation
      of the MIP type in manic patients. From a phenomenologic perspective--arising
      understandably from emotional processes-these considerations would place MIP
      mania more in the circular affective rather than in the schizophrenic domain.

PMID- 16427136
TI  - The duration of hypomania in bipolar-II disorder in private practice: methodology
      and validation.
AB  - BACKGROUND: DSM-IV 4-day minimum hypomania duration is not evidence-based.
      Epidemiologic data suggest that briefer hypomanias are prevalent in the
      community. We sought to find out the relative prevalence of short (2-3 days)
      versus long (>/=4 days) hypomanias in private practice. METHODS: 206 bipolar-II
      (BP-II) depressed outpatients (group B) and a group of 140 remitted BP-II (group
      R) were assessed with the DSM-IV Structured Clinical Interview, as modified by
      the authors. BP-II with short vs. longer hypomania were compared on such bipolar
      validators as early age at onset, depressive recurrence, atypical feature
      specifier, depressive mixed state and bipolar family history. In addition, to
      ascertain the bipolar status of depressed patients with brief hypomanias, we
      included a comparison group of 178 major depressive disorder (MDD) patients
      assessed when depressed. RESULTS: 27-30% of hypomanias (depending on whether
      assessment occurred when patients were depressed or in remission) had 2-3-day
      duration; 72% lasted less than 4 weeks. Except for the atypical feature
      specifier, BP-II with short vs. BP-II with longer hypomania were not
      significantly different on bipolar validators. Moreover, BP-II with short, like
      its longer hypomanic counterpart, was significantly different from the comparison
      MDD group on all bipolar indicators. LIMITATIONS: Single interviewer and
      retrospective evaluation of duration of hypomania. CONCLUSIONS: As BP-II patients
      almost never present clinically in a hypomanic episode, the retrospective
      assessment of the duration of these episodes is clinically unavoidable. Most
      hypomanias last from 2 days to a few weeks. BP-II with shorter vs. longer
      hypomanias had significantly higher rates of females, comorbidity and atypical
      features, but were otherwise indistinguishable on crucial bipolar validators.
      Furthermore, such validators, including bipolar family history, robustly
      distinguished BP-II with short hypomanias from the MDD group. The conservative 4
      day threshold would misclassify one out of three BP-II as MDD. Such
      misclassification has relevant implications for treatment and outcome, as well as
      clinical research methodology for depressive and bipolar disorders.

PMID- 16427137
TI  - Toward a definition of a cyclothymic behavioral endophenotype: which traits tap
      the familial diathesis for bipolar II disorder?
AB  - BACKGROUND: Although the cyclothymic temperament appears to be related to the
      familial diathesis of bipolar disorder, exhibiting high sensitivity for bipolar
      II (BP-II) disorder, it is presently uncertain which of its constituent traits
      are specific for this disorder. METHODS: In a sample of 446 major depressive
      patients (BP-II and unipolar), in the French National EPIDEP study, the
      cyclothymic temperament was assessed by using clinician- and self-rated scales.
      We computed the frequency of individual traits and relative risk for family
      history of bipolarity. RESULTS: From both clinician- and self-rated scales, four
      items related to mood reactivity, energy, psychomotor and mental activity were
      significantly highly represented in the subgroup with positive family history of
      bipolarity. The item "rapid shifts in mood and energy" obtained the highest
      relative risk (OR=3.42) for positive family history of bipolarity. CONCLUSION:
      These findings delineate those cyclothymic traits which are most likely to tap a
      familial-genetic diathesis for BP-II, thereby identifying traits which can best
      serve as a behavioral endophenotype for this bipolar subtype. Such an
      endophenotype might underlie the cyclic course of bipolar disorder first
      described in France 150 years ago by Falret and Baillarger.

PMID- 16427138
TI  - The incidence of pre-eclampsia among couples consisting of Japanese women and
      Caucasian men.
AB  - Recent data from Hiby (2004) have suggested that a combination of maternal killer
      immunoglobulin receptor (KIR) AA genotype and fetal HLA-C2 genotype increases the
      risk of pre-eclampsia. Different human populations have a reciprocal relationship
      between KIR AA frequency and HLA-C2 frequency. Japanese people have highest
      frequency of KIR-AA alleles and lowest frequency of HLA-C2 alleles. However,
      Caucasians have a moderate frequency of KIR-AA and HLA-C2 alleles. If this
      hypothesis is correct, the incidence of pre-eclampsia among couples consisting of
      Japanese women and Caucasian men should be higher than that among couples
      consisting of Japanese women and Japanese men. Therefore, we investigated the
      incidence of pre-eclampsia among 324 couples consisting of Japanese women and
      Caucasian men. The incidence of pre-eclampsia in these couples consisting of
      Japanese women and Caucasian men was similar to that in Japanese women and
      Japanese men. Our data do not support that of Hiby et al. [Hiby, S.E., Walker,
      J.J., O'Shaughnessy, K.M., Redman, C.W.G., Carrington, M., Trowsdale, I.,
      Moffett, A., 2004. Combinations of maternal KIR and fetal HLA-C genes influence
      the risk of pre-eclampsia and reproductive success. J. Exp. Med. 200, 957-965],
      although we did not check the haplotypes for HLA-C and KIR.

PMID- 16427139
TI  - Metallothionein expression and infiltration of cytotoxic lymphocytes in uterine
      and tubal implantation sites.
AB  - INTRODUCTION: In spite of increasing number of immune cells in the endometrium
      during the decidualization, the integrity of endometrial tissue in each menstrual
      cycle is maintained by adaptive changes in expression of several factors that
      regulate activity of immune cells and concomitant hormonal alterations during the
      menstrual cycle. This regulatory function of endometrium is also related to
      resistance to apoptosis, in which metallothionein (MT) may play a role. MATERIALS
      AND METHODS: Study group included 26 women with spontaneous abortion and 18
      patients with tubal ectopic pregnancy. Control group included 17 women whose
      endometrial tissue samples were taken during the normal secretory cycle phase.
      Expression of metallothionein (MT), CD56 and CD69 were assessed in tissue samples
      by immunohistochemistry. RESULTS: The number of CD56-positive cells was
      significantly higher in women with ruptured than unruptured ectopics. MT
      expression was higher in tubal mucosa distant from the implantation site in
      ruptured compared to unruptured ectopics. It was found also to be significantly
      lower than in decidua taken from women with spontaneous abortion. CD69 expression
      was similar in women with spontaneous abortion as well as patients with ruptured
      ectopics compared to the control group. On the other hand, CD69 expression in
      unruptured ectopics was significantly lower than in women with spontaneous
      abortion and the control group. CONCLUSION: The concentration of immune cells and
      increase of their activity in tubal mucosa, with insufficient protection against
      immune-mediated apoptosis assessed by MT expression, might result in tubal
      rupture during ectopic pregnancy.

PMID- 16427140
TI  - Association of a maternal CD14 -159 gene polymorphism with preterm premature
      rupture of membranes and spontaneous preterm birth in multi-fetal pregnancies.
AB  - CD14, the major receptor for bacterial lipopolysaccharide (LPS) as well as other
      microbial antigens, is a component of the innate immune system. We hypothesized
      that a single nucleotide C>T polymorphism at position -159 in the CD14 gene that
      results in elevated CD14 production would influence susceptibility to preterm
      premature rupture of membranes (PPROM) and spontaneous preterm birth (SPTB) in
      multi-fetal pregnancies. DNA from 107 mother-twin and three mother-triplet pairs
      was analyzed. Pregnancy outcomes were obtained after completion of testing.
      CD14*T homozygosity was present in 39.3% of 28 women whose pregnancies ended with
      PPROM, as opposed to 18.1% of 72 pregnancies without a SPTB (P=0.03). There was
      no relation between the fetal CD14 genotype and PPROM. The likelihood ratio (LR)
      for PPROM was 2.2 for women homozygous for CD14*T. The LR increased to 3.3 and
      3.6 if the CD14 polymorphism was present in combination with previously
      determined maternal polymorphisms in the genes coding for the inducible 70kDa
      heat shock protein (hsp70-2) and the interleukin-1 receptor antagonist (IL1RN),
      respectively. Thus, an enhanced maternal pro-inflammatory immune response to LPS
      may increase susceptibility to PPROM in multi-fetal pregnancies.

PMID- 16427141
TI  - Cognitive impairment but preservation of sexual dimorphism in cognitive abilities
      in chronic schizophrenia.
AB  - Neurocognitive impairment in schizophrenia is well established, though sex
      differences on cognitive tasks have produced equivocal findings. The present
      study was designed to examine performance of schizophrenia patients on a sexually
      dimorphic cognitive battery. The cognitive battery comprising tests of spatial
      (mental rotation, computerized version of the Benton Judgment of Line
      Orientation) and verbal abilities (phonological and semantic fluency) was
      administered to men (n = 22) and women (n = 21) with schizophrenia and healthy
      controls (n = 21 men and 21 women). A series of multivariate analyses showed that
      the patient group performed worse than controls on all the cognitive tasks.
      Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks
      favoring women remained. Within the patient sample, correlational data
      demonstrated that earlier age at onset of illness related to poorer spatial
      performance. It is concluded that normal sexual dimorphism is undisturbed on both
      spatial and verbal tasks by the schizophrenia disease process.

PMID- 16427142
TI  - Humor perception deficits in schizophrenia.
AB  - Humor is a complex cognitive process that could be used to elucidate subtle
      cognitive deficits. Significant deficits in humor perception were observed among
      23 outpatients with schizophrenia compared with 20 controls matched for age,
      gender and education, using a 128-item humor test.

PMID- 16427143
TI  - How special is a pathogenic CNS autoantigen? Immunization to many CNS self
      antigens does not induce autoimmune disease.
AB  - Recent work has shown neuro-protective effects of immunization with self-CNS
      antigens in animal models of Alzheimer's disease, prion diseases and CNS trauma.
      The major concern with such an approach is the inadvertent induction of
      autoimmune disease. The present work was initiated to study the incidence of
      autoimmune disease associated with the induction of T cell autoimmunity to a
      panel of 70 peptides derived from CNS proteins. Using a MHC class II motif
      developed in our laboratory to identify candidate peptides, we selected 70
      peptides from 40 different CNS proteins. The proteins were selected randomly and
      represented various biological functions (surface receptors, structural proteins,
      synaptic proteins, neurodegeneration related proteins). Each peptide was
      emulsified in CFA and injected to autoimmune-prone Lewis rats. Immunogenicity was
      verified by peptide-specific LN cell proliferation. In addition, T cell lines
      were generated for many peptides and tested by adoptive transfer. Except for the
      previously reported pathogenicity of beta-synuclein, none of the 68 peptides from
      39 proteins was found to induce CNS disease in recipient rats. These findings
      underscore the efficiency of immunological regulation in preventing CNS
      autoimmune disease, and confirm the uniqueness of the well-known pathogenic CNS
      auto-antigens.

PMID- 16427144
TI  - Association of human metapneumovirus with acute otitis media.
AB  - OBJECTIVE: Human metapneumovirus (hMPV) is a recently described paramyxovirus
      that has been associated with acute upper and lower respiratory infection (LRI)
      in infants and children worldwide. We previously observed that one-third of the
      children with hMPV-associated LRI had been diagnosed with a concomitant acute
      otitis media (AOM). In the current study, we sought to investigate an association
      between hMPV and children presenting with AOM as a primary diagnosis. METHODS: We
      used realtime RT-PCR for hMPV to retrospectively test 144 paired nasal wash (NW)
      and middle ear fluid (MEF) specimens that had been prospectively collected from
      children with AOM during a 3-year period from 1990-1992. RNA was extracted from
      archived, frozen samples and realtime RT-PCR for hMPV was performed. RESULTS: We
      detected hMPV in 8/144 (6%) NW and 1/144 MEF. Several of the children still
      tested positive for hMPV in NW 3 days later, showing persistent virus shedding.
      All were detected from November-May and six had bacterial co-pathogens. Two of
      the eight (25%) hMPV-infected children had no bacterial pathogen isolated,
      suggesting that hMPV may be associated with AOM as a sole pathogen. CONCLUSIONS:
      These data show that hMPV is associated with a proportion of AOM and thus has
      additional morbidity and healthcare impact related to these illnesses.

PMID- 16427145
TI  - Conditioning method determines patterns of c-fos expression following novel taste
      illness pairing.
AB  - Conditioned taste aversions (CTAs) can be established by exposing rats to a novel
      taste CS through a bottle or through intra-oral (IO) infusion. Lesion studies
      suggest differences between the two methods in their engagement of brain
      circuits, as excitotoxic amygdala lesions have no effect on bottle-conditioned
      CTAs, but eliminate CTAs produced using IO infusion. Fos-like immunoreactivity
      (FLI) was used to compare patterns of brain activation after pairing CS taste and
      US drug using bottle and IO methods. Conditioning rats using the bottle method
      was associated with widespread elevations in FLI throughout the putative CTA
      circuit (basolateral and central nuclei of amygdala, insular cortex and nucleus
      of the solitary tract). In contrast, IO conditioning led to activation only in
      the central nucleus of amygdala. This supports the suggestion of differences in
      aversion processing as a function of conditioning method and may explain the
      greater reliance on amygdala of IO-conditioned CTAs due to engagement of a less
      distributed neural network.

PMID- 16427146
TI  - Plasma steroid hormone concentrations, aromatase activities and GSI in ranid
      frogs collected from agricultural and non-agricultural sites in Michigan (USA).
AB  - The triazine herbicide atrazine has been hypothesized to disrupt sexual
      development in frogs by up-regulating aromatase activity, resulting in greater
      estradiol (E2) concentrations and causing feminization in males. The goal of this
      study was to collect native ranid frogs from atrazine-exposed ponds and determine
      whether relationships exist between measured atrazine concentrations and the
      gonadosomatic index (GSI), plasma concentrations of testosterone (T), E2 or 11
      ketotestosterone (KT), or with aromatase activity. In the summer of 2002 and
      2003, adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana)
      and Northern leopard frogs (R. pipiens) were collected from areas with extensive
      corn cultivation and areas where there was little agricultural activity in south
      central Michigan. Atrazine concentrations were below the limit of quantification
      at non-agricultural sites. Atrazine concentrations did not exceed 2 microg/L at
      most agricultural sites, but a concentration of 250 microg atrazine/L was
      measured in one sample from one site in 2002. Plasma steroid concentrations
      varied among locations. Aromatase activity was measurable in less than 11% of
      testes in adult males, and in less than 4% of testes in juvenile males. Median
      aromatase activities in ovaries of adult females ranged from 3 to 245 pmol/h/mg
      protein, and maximum activities were 2.5-fold greater in juveniles than in
      adults. Atrazine concentrations were not significantly correlated with any of the
      parameters measured in this study. These results indicate that atrazine does not
      up-regulate aromatase in green frogs in the wild, and does not appear to affect
      plasma steroid hormone concentrations.

PMID- 16427149
TI  - Seasonal variation of bulk milk somatic cell counts in UK dairy herds:
      investigations of the summer rise.
AB  - Individual cow somatic cell count (SCC) patterns were explored over a one year
      period in 33 dairy herds to investigate the reason for a summer rise in bulk milk
      somatic cell counts (BMSCC). Cow test day somatic cell counts were categorised
      according to the magnitude of change since the previous test day reading, to
      examine which categories were responsible for the summer increase. Multilevel
      models using Markov chain Monte Carlo methods were specified to estimate the
      number of somatic cells/ml produced by different cell count categories. Stage of
      lactation and parity were accounted for in the models. There was an increase in
      the proportion of cows that remained above 200,000 cells/ml for two consecutive
      recordings in summer and this group of cows were responsible for 70.8% of the
      increase in somatic cells/ml produced from May to September compared with October
      to March. There was no evidence that a greater new infection rate (somatic cell
      counts moving from below 100,000 cells/ml to over 200,000 cells/ml) contributed
      to the increased summer bulk milk somatic cell counts. There was no indication
      that a general small increase in all somatic cell counts played an important role
      in the increased summer somatic cell counts. Markov chain Monte Carlo methods
      provided a valuable and flexible platform for parameter estimation in reasonably
      complex multilevel models.

PMID- 16427148
TI  - Depression as prognostic factor: 6 months follow-up in a geriatric institution.
AB  - Depression in the elderly and especially in the demented elderly is common, but
      it is unclear to what extent depression affects the prognosis of dementia. We
      performed a 6 months follow-up on the elderly to evaluate the effect of
      depression on the prognosis of dementia. Among the residents in a Korean
      geriatric institution, a total of 141 elderly residents were included in this
      study. Those residents who had geriatric depression scale (GDS) scores over 20
      were considered as having depression. The subjects were assessed at baseline and
      at 6 months later with the Korean Mini-Mental State Examination (K-MMSE),
      Clinical Dementia Rating (CDR) and Barthel index (BI). For all the 141 subjects,
      the changes of the K-MMSE, CDR and BI scores were first compared between the
      depressed and non-depressed groups. Then, for the 58 depressed subjects
      subdivided into three groups (36 subjects in the non-demented group, 14 subjects
      in the Alzheimer disease (AD) group and 8 subjects in the vascular dementia (VaD)
      group), the changes of the scores among the three groups were compared. For all
      subjects, the changes of the K-MMSE and CDR scores were more severe in the
      depressed group than in the non-depressed group. For the 58 depressed subjects,
      the changes were significantly different among the three groups (p=0.02 for the K
      MMSE, p<0.001 for the CDR), and the changes were the most severe in the VaD
      group. For the elderly, depression has a significant influence on the cognitive
      deterioration. Moreover, the effect of depression on the cognitive dysfunction
      and on the prognosis of dementia is more severe in the demented elderly, and
      especially for the VaD patients.

PMID- 16427150
TI  - Serum-free hybridoma culture: ethical, scientific and safety considerations.
AB  - Despite considerable progress in the development of cell culture techniques,
      including the development of the serum- and protein-free media that now routinely
      support hybridoma and mammalian cell growth, fetal bovine serum (FBS)
      supplemented media are still commonly used: a practice that raises ethical,
      scientific and safety concerns. The use of FBS in hybridoma culture media is
      examined here, with regards to the development and production of monoclonal
      antibodies (mAbs), and it is our recommendation that researchers adopt serum-free
      cell culture methods to reduce animal use in this area.

PMID- 16427151
TI  - An activation of parvocellular oxytocinergic neurons in the paraventricular
      nucleus in oxytocin-induced yawning and penile erection.
AB  - Intracerebroventricular (ICV) or PVN local injections of oxytocin induce yawning
      and penile erection, for which a positive feedback mechanism for the PVN
      oxytocinergic activation is suggested, but this had not been directly
      substantiated in vivo. We have assessed the behavioral effects and activity of
      oxytocinergic neurons with double-staining for c-Fos and oxytocin in the PVN
      after ICV administration of oxytocin in adult male rats. ICV oxytocin injections
      (50 and 200 ng) dose-dependently induced yawning and penile erection and
      significantly increased the percentage of c-Fos positive oxytocin neurons in the
      medial, dorsal and lateral parvocellular subdivision of the PVN. However,
      increases in the magnocellular portion were not significant. We also found that
      lithium chloride (LiCl, 0.5 and l.0 mEq), a compound known to activate
      oxytocinergic neurons, also significantly increased the percentage of c-Fos
      positive oxytocin neurons in all PVN portions. However, LiCl did not induce
      yawning and penile erection, but counteracted the oxytocin-induced yawning and
      penile erection. These results suggest that if the activation of oxytocinergic
      neurons in the PVN is important for mediating oxytocin-induced yawning and penile
      erection, a selective activation of parvocellular oxytocinergic neurons in the
      PVN is likely to be involved.

PMID- 16427152
TI  - Behavioural anomalies in mice evoked by "Tokyo" disruption of the Vitamin D
      receptor gene.
AB  - Vitamin D is a steroid hormone with many important functions in the brain,
      mediated through the nuclear Vitamin D receptor (VDR). Mounting clinical data
      link VDR mutations to various psychiatric phenotypes. We have reported previously
      that mutant mice lacking functional VDR ("Tokyo" VDR mutant mice) display several
      behavioural anomalies, including high anxiety and aberrant grooming. Given the
      important role of Vitamin D and VDR in brain development and functioning, we
      hypothesized that several other important behavioural domains may be affected by
      disruption of the VDR gene in mice. Here we report that VDR mutants display
      unaffected depressive-like behaviour, but show abnormal social behaviours,
      reduced social barbering and aggressiveness, impaired nest building and aberrant
      maternal (pup neglect, cannibalism) behaviours. Taken together, these findings
      confirm the important role postulated for the VDR in the regulation of behaviour,
      and suggest the mice lacking functional VDR may be a useful tool to model
      different brain disorders.

PMID- 16427153
TI  - Screening of 42 Bacillus isolates for ability to ferment soybeans into dawadawa.
AB  - Forty-two cultures of Bacillus species isolated from soybean dawadawa were
      screened for their proteolytic activity on Skim Milk Agar, amylolytic activity on
      Starch Agar, and ability to grow on Soybean Agar. Distinct differences were
      observed between the cultures for all the criteria. Eleven isolates were selected
      for laboratory fermentation trials and each produced soybean dawadawa which was
      found acceptable by a taste panel. The pH of the samples, which increased from
      6.37-6.58 to 8.22-8.85 during fermentation, were significantly different at P< or
      =0.05 for the different cultures. In the fermented samples, Bacillus counts
      exceeded 10(9) cfu/g, with the population of only one sample being significantly
      different at P< or =0.05. A market focus group familiar with soybean dawadawa
      selected Bacillus subtilis 24BP(2) and B. subtilis FpdP(2) as the best potential
      starter cultures. A taste panel found no significant differences in overall
      acceptance between soybean dawadawa either fermented spontaneously or with B.
      subtilis 24BP(2) and also between soybean dawadawa fermented with either B.
      subtilis 24BP(2) or B. subtilis FpdP(2).

PMID- 16427154
TI  - Detection of the frequency, antimicrobial susceptibility, and genotypic
      discrimination of Aeromonas strains isolated from municipally treated tap water
      samples by cultivation and AP-PCR.
AB  - The frequency, antibiotic susceptibility, and genotypic discrimination of
      Aeromonas strains isolated from municipally treated drinking tap water
      distribution systems were investigated in this study. We have analyzed 148 tap
      water samples collected from 8 different locations by bacterial cultivation and
      arbitrarily primed polymerase chain reaction (AP-PCR). Gram negative, hemolytic,
      oxidase (+) and catalase (+) bacterial colonies were applied to the study.
      Identification of bacterial colonies was done by conventional biochemical method
      and API ID 20E panel (BioMerieux-France). Molecular epidemiological
      discrimination of the isolates was done by AP-PCR. Aeromonas spp. was detected in
      6 of 148 (4%) tap water samples from 8 different locations. Five isolates were
      identified as Aeromonas hydrophila and one isolate was identified as Vibrio
      fluvialis by conventional biochemical method. These data were also confirmed by
      API 20E panel. One of 6 isolates was resistant to gentamicin, 2 of 6 isolates
      were resistant to trimethoprim/sulfamethoxazole, 4 of 6 isolates were resistant
      to ampicillin and ampicillin-sulbactam and all of 6 isolates were resistant to
      cephalothin. All isolates were found to be susceptible to amikacin, aztreonam,
      ceftazidime, ceftriaxone, ciprofloxacin. All 6 strains of Aeromonas were
      discriminated by AP-PCR and were determined that all isolates were from different
      genotypic sources. Although the frequency of the isolates was under the standard
      limits, the results indicate that hemolytic A. hydrophila are present in
      municipally treated tap water samples in Mersin City. While all strains were
      genotypically distinct, all of them were resistant to first generation beta
      lactam antibiotics tested in this study.

PMID- 16427155
TI  - HIV p17 reverses the anti-inflammatory activity of IL-4 on IL-15 stimulated
      monocytes and modulates their ability to secrete MIP-1 alpha.
AB  - Monocytes play a central role in the immune system by producing and reacting to
      different soluble factors. Cytokine dysregulation is an hallmark in HIV-infected
      individuals and it is one of the most significant factors leading to impaired
      immunity in HIV/AIDS disease. This study investigates the possibility of
      modulation in the secretion of some inflammatory cytokines and chemokines induced
      by HIV p17 in monocytes. The results show that p17, while ineffective on resting
      monocytes, exerts an inflammatory action on IL-4 mediated inhibition of TNF-alpha
      and IFN-gamma production induced by IL-15 stimulation. In addition, p17 is able
      to reduce MIP-1alpha secretion, but unable to influence IL-6 production. The
      ability of HIV p17 to contribute to an altered pattern of secreted soluble
      factors might imply a key role for this viral protein in the development of AIDS
      pathogenesis.

PMID- 16427147
TI  - Schistosoma mansoni CBP/p300 has a conserved domain structure and interacts
      functionally with the nuclear receptor SmFtz-F1.
AB  - Metazoan species diversification in general and the adaptation of parasites to
      their life-style in particular are due, not only to the evolution of different
      structural or metabolic proteins, but also to changes in the expression patterns
      of the corresponding genes. In order to explore the conservation/divergence of
      transcriptional regulation in the platyhelminth parasite Schistosoma mansoni, we
      are studying the structures and functions of transcriptional mediators. CREB
      binding protein (CBP) and p300 are closely related transcriptional coactivators
      that possess histone acetyltransferase (HAT) activity that can modify chromatin
      to an active relaxed state. They are also thought to link transcription factors
      to the basic transcriptional machinery and to act as integrators for different
      regulatory pathways. Here we describe the cloning and functional characterization
      of S. mansoni CBP. SmCBP1 comprises 2093 amino acids and displays a conserved
      modular domain structure. The HAT domain was shown to acetylate histones with a
      marked activity toward H4. Functional studies showed that SmCBP1 could interact
      physically with the nuclear receptor SmFtz-F1 and also potentiated its
      transcriptional activity in the CV-1 cell line. Screening of the EST and genomic
      sequence databases with the SmCBP1 sequence allowed us to characterize a second
      CBP gene in S. mansoni. SmCBP2 shows a high degree of sequence identity to
      SmCBP1, particularly in the HAT domain. Phylogenetic studies show that these
      peptides are more closely related to each other than to either mammalian CBP or
      p300, suggesting that they derive from a platyhelminth-specific duplication
      event. Both genes are expressed at all life-cycle stages, but differences in
      their relative expression and structural variations suggest that they play
      distinct roles in schistosome gene regulation.

PMID- 16427156
TI  - Performance of serum marker panels for liver fibrosis in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Chronic hepatitis C (CHC) is characterised by hepatic fibrosis,
      used as a proxy measure of prognosis. Liver biopsy is a flawed reference standard
      and serum markers of fibrosis offer an attractive alternative. METHODS: A
      systematic review was conducted to assess the performance of panels of serum
      markers of hepatic fibrosis in CHC, incorporating analyses placing markers in a
      clinical context. RESULTS: 14 studies were included with 10 different panels.
      Median AUC in validation populations was 0.77 and training populations 0.81.
      Likelihood ratios (LR) ranged from -LR 0.1 to 0.9, + LR 1.2 to 33.1, diagnostic
      odds ratios (DOR) were 9.0 (median) with a range of 5 to 27- mostly below values
      of robust tests. Tests perform with either high sensitivity with low specificity
      or vice versa. Cut-off levels that gave clinically relevant predictive values for
      the presence/absence of significant fibrosis were applicable to 35% of the
      population. CONCLUSIONS: Serum markers can rule-in or rule-out fibrosis in up to
      35% of patients, but cannot differentiate stages of fibrosis reliably.
      Improvement of index and reference test in needed including evaluation of
      clinical outcomes as reference. Improved test reporting is needed to derive LR
      and DOR as performance indicators.

PMID- 16427157
TI  - Depression, anemia and health-related quality of life in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Hepatitis C (HCV) infected patients have significant health
      related quality of life (HRQL) impairment which worsens during anti-viral
      therapy. Our aim was to examine the association of HRQL with treatment-induced
      depression and anemia. METHODS: Two hundred and seventy-one HCV patients who
      received pegylated interferon alfa 2b and ribavirin were included. Data on HRQL,
      depressive symptoms, laboratory values and socio-demographic characteristics were
      collected. RESULTS: Mean age was 47.1+/-6.5, 69% were male, and 73% were White.
      HCV patients' HRQL declined during anti-viral therapy but returned to or exceeded
      baseline levels within 24 weeks of completion. Anemia and depression were both
      associated with HRQL impairment. The effects of depression on HRQL were strong;
      once depression scores were included other factors were no longer significant.
      Patients' depressive symptoms tended to increase during the initial half of
      treatment regimen. Those with higher body mass index (BMI), cirrhosis, and women
      reported more HRQL impairments. HRQL scales were generally not associated with
      alcohol abuse, age, race, ALT and HCV RNA levels. CONCLUSIONS: Anti-viral therapy
      for HCV is associated with diminished HRQL. Although anemia and depression were
      associated with this impairment, depression was the most consistent predictor.
      Future studies are needed to see whether proactive management of these side
      effects can improve patients' HRQL and the efficacy of antiviral therapy for
      hepatitis C.

PMID- 16427158
TI  - Pituitary adenylate cyclase-activating peptide (PACAP) stimulates production of
      interleukin-6 in rat Muller cells.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP) is known to regulate not
      only neurons but also astrocytes. Here, we investigated, both in vitro and in
      vivo, the effects of PACAP38 on rat Muller cells, which are the predominant glial
      element in the retina. Muller cells isolated from juvenile Wistar rats were
      treated with PACAP38 or PACAP6-38, a PACAP selective antagonist. Cell
      proliferation was determined by measuring the incorporation of bromodeoxyuridine
      with ELISA. Interleukin-6 (IL-6) levels in the culture medium were determined by
      a bioassay using B9 cells, IL-6 dependent hybridoma. In adult Wistar rats, the
      expression of IL-6 in the retina after intravitreal injection of PACAP38 (10
      pmol) was assessed by immunohistochemistry. PACAP38 stimulated IL-6 production in
      Muller cells at a concentration as low as 10(-12) M, which did not induce cell
      proliferation. This elevation of IL-6 production was inhibited by PACAP6-38.
      Radial IL-6 expression was observed throughout the retina at 2 and 3 days after
      PACAP38 injection. These data demonstrate that Muller cells are one of the target
      cells for PACAP. IL-6, which is released from Muller cells with stimulation by
      PACAP, may play a significant role in the retina.

PMID- 16427159
TI  - Brain 5-HT synthesis in the Flinders Sensitive Line rat model of depression: an
      autoradiographic study.
AB  - Alterations of serotonin (5-HT) levels and serotonergic transmission have been
      associated with depression. 5-HT synthesis is an important factor of serotonergic
      neurotransmission that may also be altered in depression. Many studies of the
      relationships between brain serotonergic functions and affective disorders have
      been performed in different animal models. In this study, brain regional 5-HT
      synthesis was examined using the alpha-[(14)C]methyl-L-tryptophan (alpha-MTrp)
      autoradiographic method in a genetic rat model of depression, Flinders Sensitive
      Line (FSL) rats, and was compared to both the Flinders Resistant Line (FRL) rats
      and the control Sprague-Dawley (SD) rats. The plasma concentration of free
      tryptophan in the FSL rats was not significantly different (p > 0.05; ANOVA and
      post-hoc Bonferroni correction) when compared to that of the FRL and SD rats. The
      FSL rats had significantly lower 5-HT synthesis (one sample two-tailed t-test on
      the ratio) than both the FRL and SD rats (the mean ratios were 0.78 +/- 0.12 and
      0.73 +/- 0.15, respectively). Overall, the 5-HT synthesis in the FRL rats was not
      significantly different (p > 0.05) from that in the SD rats (one sample two
      tailed t-test on the ratio and the mean ratio was 0.93 +/- 0.13). Studies of
      individual brain structures, such as the raphe nuclei and their many terminal
      areas, including the nucleus accumbens, cingulate and frontal cortex,
      hippocampus, amygdala, and thalamus revealed significant reductions (typically 25
      50%) in 5-HT synthesis in the FSL rats compared to the non-depressive FRL and SD
      rats. These results suggest that significantly reduced 5-HT synthesis in the
      raphe nuclei and limbic areas in FSL rats may contribute to their depressive
      features.

PMID- 16427160
TI  - Age- and stage-dependent glyoxalase I expression and its activity in normal and
      Alzheimer's disease brains.
AB  - The reaction of lysine and arginine residues of proteins with 1,2-dicarbonyl
      compounds result in the formation of advanced glycation end products (AGEs).
      Accumulation of AGEs is a characteristic feature of the aging brain and
      contributes to the development of neurodegenerative diseases such as Alzheimer's
      disease (AD). Therefore, it is of particular interest to study the cellular
      defense mechanisms against AGE formation and particularly the detoxification of
      their precursors. AGE precursor compounds such as methylglyoxal and glyoxal were
      cellulary detoxified by the glyoxalase system, consisting of glyoxalases I and
      II. Glyoxalase I levels are diminished in old aged brains but elevated in AD
      brains. However, it is still unknown how glyoxalase I level of AD brains changes
      in a disease and in an age-dependent manner. Therefore, we investigated the AD
      stage- and the age-dependent levels of glyoxalase I in the Brodmann area 22 of AD
      brains (n=25) and healthy controls (n=10). Our results obtained from RT-PCR
      reveal reducing glyoxalase I RNA levels with advancing stage of AD and with
      increasing age. Western Blot analysis indicates that in comparison to healthy
      controls, glyoxalase I protein amounts are 1.5-fold increased in early AD
      subjects and continuously decrease in middle and late stages of AD. The
      glyoxalase I protein amounts of AD patients also decrease with age. Results
      obtained from glyoxalase I activity measurement show 1.05-1.2-fold diminished
      levels in AD brains compared to healthy controls and no significant decrease
      neither with the stage of AD nor with age. The immunohistochemical investigations
      demonstrate an elevated number of glyoxalase I stained neurons in brains of early
      and middle but not in late AD subjects compared to age-matched healthy controls.
      In addition, the stage-dependent immunohistochemical investigation demonstrates
      that with reduced glyoxalase I staining AGE deposits prevail, specifically in
      late stage of AD. In conclusion, the decrease of glyoxalase I expression with
      increasing AD stage might be one reason for methylglyoxal-induced neuronal
      impairment, apoptosis, and AGE formation in plaques and tangles.

PMID- 16427162
TI  - [Rheumatoid purpura in elderly: case report].

PMID- 16427161
TI  - Adenosine receptor modelling. A1/A2a selectivity.
AB  - Three-dimensional models of the A(1) and A(2a) adenosine receptors (AR) were
      constructed by means of a homology procedure, using bovine rhodopsin as a
      template. In order to validate the two models, a docking analysis of selective
      agonists was carried out. The study shows that A(1)/A(2a) selectivity is mainly
      influenced by the different ability of the two receptors to give lipophilic
      interactions, instead of giving different H bonds. The binding site cavity of the
      A(1)AR is smaller than that of the A(2a)AR, and for this reason, less bulky
      ligands like CPA are able to give close interactions with the A(1)AR, unlike
      larger ligands such as CGS-21680. The different dimensions of the binding site
      cavity could be due to the presence of three residues of proline, which cause a
      different rearrangement of the TM, thus modifying the side chain disposition
      inside the inter-helix channel.

PMID- 16427163
TI  - Waning antibodies in measles and rubella vaccinees--a longitudinal study.
AB  - The evolution of measles- and rubella-specific serum IgG was followed in a
      longitudinal study in 224 young adolescent vaccinees, with or without boost
      vaccination before or during the 6.8-year observation period. Antibody titres
      were monitored by enzyme immuno assay (Enzygnost, Dade-Behring). After
      revaccination (second dose) rubella seropositivity rate increased from 92.1 to
      100%, whereas measles seroprevalence (about 90%) did not significantly change
      between the paired sera. Significantly higher IgG (> three-fold) in the second
      serum of 5.2% (measles) and 7.8% (rubella) of participants with low antibodies
      (measles: < 1500 mIU; rubella < 40 IU) in first serum, suggest a secondary immune
      response (SIR) during the study period, only partially explained by
      revaccination. Excluding individuals with SIR, minimal annual antibody decay
      rates of -2.9% (confidence interval, CI: -0.7 to -4.8%) for rubella and -1.6%
      (CI: -0.1 to -3%) for measles were determined in participants with single dose
      vaccination. Thus, two-dose vaccination was adequate to protect women from
      rubella infection at least during childbearing age. Similarly only few
      individuals may become seronegative for measles again after successful
      vaccination due to minimal waning of low antibody levels (< 1500 mIU). However,
      as a result of a more rapid decay of high-titre (> 1500 mIU) antibodies (
      2.4%/year), many vaccinees may eventually become susceptible to vaccine-modified
      measles (VMM) and consequently complicate measles control strategies.

PMID- 16427164
TI  - Post-depositional redistribution and gradual accumulation of 137Cs in a riparian
      wetland ecosystem in Sweden.
AB  - After the Chernobyl accident, high activity concentrations of (137)Cs (>1 MBq m(
      2)) were detected in a riparian swamp in the central-eastern part of Sweden. The
      objective of this study was to clarify the redistribution processes behind the
      accumulation of (137)Cs in the wetland. A mass balance budget of (137)Cs was
      calculated based on soil and sediment samples and reports in the literature.
      Results showed that accumulation occurred over several years. Of all the (137)Cs
      activity discharged between 1986 and 2002 from the upstream lake, 29% was
      estimated to be retained in the wetland. In 2003, measurements showed that 17 kBq
      m(-2) sedimented on the stream banks of the wetland. Continuing overbank
      sedimentation by spring flooding prolongs the time that the wetland will contain
      high activity concentrations of (137)Cs. Consequently, organisms living in
      wetlands serving as sinks for (137)Cs may become exposed over long time periods
      to high activity concentrations.

PMID- 16427165
TI  - Ground reaction force data in functional ankle instability during two cutting
      movements.
AB  - BACKGROUND: Functional instability of the ankle joint may interfere with proper
      execution of quick cutting movements in sports. Previous studies have provided
      information regarding the ground reaction force characteristics in such movements
      in healthy players but no research was found in players with ankle instability.
      The purpose of this study was to evaluate and compare ground reaction forces in
      functionally unstable ankles with healthy ones during two cutting movements, the
      v-cut and the defensive shuffle. METHODS: Fifteen male basketball players with
      self reported unilateral functional instability and 17 matched controls,
      performed three v-cuts and three defensive shuffles on two synchronised force
      platforms. Both joints were tested and ground reaction forces analysed by an one
      way ANOVA for independent groups to test differences between groups, and paired t
      test to examine differences within affected players. FINDINGS: Unstable ankles,
      demonstrated significantly greater first vertical force peak, than contralateral
      unaffected joints (P < or = 0.05) and lower relative time to peak than controls
      (P< or = 0.05), during v-cut movement. No significant differences were seen in
      variables between groups during lateral shuffling. INTERPRETATION: Unstable
      ankles demonstrated altered patterns of ground reaction forces, with a rapid
      onset of high vertical force during the first millisecond post-impact, while the
      medial component was unchanged. Although the increased vertical forces are
      considered predisposing factors to repeated injury, this finding is likely a
      neuromuscular response making the ankle joint more stable avoiding excessive
      inversion forces.

PMID- 16427166
TI  - Low intensity pulsed ultrasound increases the matrix hardness of the healing
      tissues at bone-tendon insertion-a partial patellectomy model in rabbits.
AB  - BACKGROUND: This study evaluated the low intensity pulsed ultrasound enhancement
      on matrix hardness of the healing tissues at the bone-tendon junction. METHODS:
      Sixteen 18 week-old mature female rabbits were used. An established transverse
      partial patellectomy was performed at the distal one-third of the patella.
      Animals were then divided according to their body weight into ultrasound group (n
      = 8) with daily treatment of low intensity pulsed ultrasound and control group (n
      = 8) without ultrasound treatment. Animals were euthanized at week 8 and 16
      postoperatively to evaluate the radiographic new bone formation and the Vickers
      hardness of the matrix of the healing tissues at the bone-tendon junction.
      FINDINGS: (1) Comparing with the control group, the anterior-posterior area of
      the new bone in the ultrasound treated group was found on average to be 3.0 and
      3.1 times greater at week 8 and 16, respectively (P < 0.01). (2) The Vickers
      hardness of the new bone in ultrasound group was 11.3% (P < 0.05) significantly
      lower at week 8 but 20.0% (P < 0.05) significantly higher at week 16 as compared
      with that of the control group. (3) The Vickers hardness of the newly regenerated
      fibrocartilage zone, healing tendon, and cartilaginous metaplasia in ultrasound
      group was found higher than the control group at both week 8 and 16, but the
      difference was significant at week 16 only, being 44.1% (P < 0.05), 20.1% (P <
      0.01), and 46.4% (P < 0.01) higher, respectively. INTERPRETATION: The preliminary
      findings suggested for the first time that low intensity pulsed ultrasound
      treatment resulted in the enhancement of the matrix hardness in new bone,
      fibrocartilage, cartilaginous metaplasia, and healing tendon at the healing bone
      tendon junction. These findings can be extrapolated into clinical practice, i.e.
      the more rapid healing induced by low intensity pulsed ultrasound, the earlier
      mobilization of the affected joint. The beneficial effects on prevention of the
      musculoskeletal deterioration resulting from the prolonged immobilization would
      be therefore expected.

PMID- 16427167
TI  - Clinical and goniometric evaluation of patients with spasmodic torticollis.
AB  - BACKGROUND: Patients with cervical dystonia have been evaluated prospectively by
      the Toronto Western Spasmodic Torticollis Rating Scale and by cervical
      electrogoniometry. METHODS: Nineteen patients with cervical dystonia were
      studied. The Toronto Scale interobserver reliability was evaluated by two
      observers. An electrogoniometer was used to quantify cervical range of motion and
      velocity. The correlation between goniometric measurements and clinical
      evaluation was calculated. FINDINGS: The interobserver reliability was excellent
      for the total score (r(s) = 99) and good for the disability and the pain score (r
      > 0.88). However, global severity scale was shown to have a moderate reliability
      (r = 0.63) with r ranging from 0.37 to 0.98 for the individual items. The average
      loss of range of motion for flexion and extension, lateral bending and rotation
      was 18%, 12% and 21% respectively. For the velocity of movement, the average loss
      was proportionately greater than for the range of motion. (41%, 43% and 52%
      respectively). Correlation between the severity scale and range of motion was
      moderate but significant (r(s) = -0.52 to -0.67). Correlation between the Toronto
      severity score and the sum of movement velocities was significant for flexion
      extension and lateral bending velocity sums (r(s) = -0.51; r(s) = -0.61). The
      lateral bending and rotation velocities were significantly correlated with pain
      and total scores (r(s) = -0.51). No significant correlation was observed for the
      disability score. INTERPRETATION: Three-dimensional electrogoniometry is helpful
      to quantify the velocity of neck movements and range of motion in patients with
      cervical dystonia.

PMID- 16427168
TI  - Comparison of static and dynamic biomechanical measures in military recruits with
      and without a history of third metatarsal stress fracture.
AB  - BACKGROUND: For Royal Marine recruits in training, the third metatarsal is the
      most common site for stress fracture. Previous evidence regarding biomechanical
      factors contributing to metatarsal stress fracture development is conflicting,
      possibly due to the lack of differentiation between the metatarsals. The present
      retrospective study compares static anatomical characteristics and dynamic
      biomechanical variables for Royal Marine recruits with and without a history of
      third metatarsal stress fracture. METHODS: Ten Royal Marine recruits with a
      history of third metatarsal stress fracture were compared with control subjects
      with no previous stress fracture occurrence. Selected static anatomical variables
      were measured to describe the ankle and subtalar joints. Peak ankle dorsi-flexion
      and rearfoot eversion were measured during running. In addition, peak vertical
      and horizontal ground reaction force variables were compared for the two study
      groups. FINDINGS: No significant differences in static anatomical variables were
      identified between study groups. During running, peak rearfoot eversion was found
      to occur significantly earlier for the stress fracture group than for their
      matched controls, suggesting an increase in time spent loading the forefoot. The
      peak applied resultant horizontal force during the braking phase was directed
      significantly more laterally for the stress fracture group. In addition, the peak
      magnitude of resultant horizontal force applied during the propulsion phase was
      significantly lower for the stress fracture subjects. INTERPRETATION: The
      findings of this study highlight the importance of including dynamic
      biomechanical data when exploring variables associated with the development of
      third metatarsal stress fracture and indicate that successful interventions to
      reduce the incidence of this injury are likely to focus on forefoot function
      during braking and propulsion.

PMID- 16427169
TI  - Towards a multidisciplinary and integrated strategy in the assessment of adverse
      health effects related to air pollution: the case study of Cracow (Poland) and
      asthma.
AB  - Complex interaction between anthropogenic activities, air quality and human
      health in urban areas, such as in Cracow sustains the need for the development of
      an interdisciplinary and integrated risk-assessment methodology. In such purpose,
      we propose a pilot study performed on asthmatics and based on a combined use of a
      biomarker, such as metallothionein 2A (MT-2A) in the characterization of human
      exposure to one or a mixture of pollutants and of Geographical Information
      Systems (G.I.S.) which integrates climatic and urban anthropogenic parameters in
      the assessment of spatio-temporal dispersion of air pollutants. Considering
      global incidence of air pollution on asthma and on peripheral blood lymphocytes
      MT-2A expression should provide a complementary information on biological risks
      linked to urban anthropogenic activities. Such study would help for the
      establishment of a sustainable development in urban areas that can maintain the
      integrity of air quality and preserve human health.

PMID- 16427170
TI  - Ecotoxicity, phytotoxicity and extractability of heavy metals from different
      stabilised sewage sludges.
AB  - The presence of heavy metals in the sludges produced in wastewater treatment
      plants restricts their use for agricultural purposes. This study compares
      different types of sludges (aerobic, anaerobic, unstabilised and sludge from a
      waste stabilisation pond) in order to assess the extractability of heavy metals
      using simple extraction, water and DTPA. The stabilisation treatment undergone by
      the sludges influenced the heavy metals extractability. The least mineralised
      sludges (unstabilised and aerobic) showed higher metal extractability. The sewage
      sludges were subjected to chemical characterisation and toxicity testing
      (ecotoxicity and phytotoxicity assays) in absence of substrate, to provide a
      preliminary assessment of their suitability for land application. The ecotoxicity
      assays confirmed that no sludge constituted a hazardous waste. The sludge
      extracts had significant adverse effect on the germination index (GI) of barley
      (Hordeum vulgare L.) and cress (Lepidium sativum L.), a fact which indicates that
      some characteristics affected root growth.

PMID- 16427171
TI  - Social relations or social capital? Individual and community health effects of
      bonding social capital.
AB  - Social capital has become one of the most popular topics in public health
      research in recent years. However, even after a decade of conceptual and
      empirical work on this subject, there is still considerable disagreement about
      whether bonding social capital is a collective resource that benefits communities
      or societies, or whether its health benefits are associated with people, their
      personal networks and support. Using data from the 2000 and 2002 Health Survey
      for England this study found that, in line with earlier research, personal levels
      of social support contribute to a better self-reported health status. The study
      also suggests that social capital is additionally important for people's health.
      In both datasets the aggregate social trust variable was significantly related to
      self-rated health before and after controlling for differences in socio
      demographics and/or individual levels of social support. The results were
      corroborated in the second dataset with an alternative indicator of social
      capital. These results show that bonding social capital collectively contributes
      to people's self-rated health over and above the beneficial effects of personal
      social networks and support.

PMID- 16427172
TI  - Recent life events and suicide: a case-control study in Tallinn and Frankfurt.
AB  - The purpose of this study was to analyze the differences in the disposition and
      frequency of recent life events preceding suicide in two cities with different
      socio-political backgrounds: Tallinn in Estonia and Frankfurt/Main in Germany.
      The information about 156 suicidents in Tallinn and 163 suicidents in Frankfurt
      was compiled using the psychological autopsy technique [Shneidman, E. S. (1981).
      The psychological autopsy. Suicide and Life-Threatening Behavior, 11, 325-340;
      Jacobs, D., & Klein-Benheim, M. (1995). The psychological autopsy: A useful tool
      for determining proximate causation in suicide cases. Bulletin of American
      Academy of Psychiatry Law, 23(2), 165-182]. General population controls were
      matched by age and sex. The occurrence of recent life events was similar among
      suicidents in Tallinn (81%) and Frankfurt (77%). However, in both sites only male
      suicides had higher risk of occurrence of any life event than controls (Tallinn:
      OR'=1.9; 95% CI=1.1-3.7; Frankfurt: OR'=2.0; 95% CI=1.0-4.1) and the mean number
      of life events was significantly higher among male suicidents in Tallinn in
      comparison with controls. This may indicate that males are more sensitive to the
      rapid changes in a society undergoing transition. It seems that it is not the
      number of life events, but rather their meaning and disposition that creates the
      risk of suicide. Family discord (weighted OR=4.5; 95% CI=2.5-8.1), loss of job
      (weighted OR=2.6; 95% CI=1.0-6.4) and financial deterioration (weighted OR=2.2;
      95% CI=1.3-3.8) were more prevalent among suicides in Tallinn in comparison with
      those in Frankfurt. The most significant differences between suicides and
      controls were family discord, separation and loss of job in Tallinn and somatic
      illness in Frankfurt. These differences between the two societies, post-Soviet
      Estonia and Germany, could be explained by the different positions of Estonia and
      Germany on the survival/self-expression dimensions recorded by the World Value
      Survey. People in Estonia tend to emphasize economic and physical security above
      all other goals, and feel threatened by the changes taking place in society. In
      Germany, good health is considered a necessity for a consumer and self-expressive
      style of life, and poor health is perceived as a serious threat to the quality of
      life in a post-materialistic value system.

PMID- 16427173
TI  - Do religious/spiritual coping strategies affect illness adjustment in patients
      with cancer? A systematic review of the literature.
AB  - The present paper systematically reviews studies examining the potential
      beneficial or harmful effects of religious/spiritual coping with cancer. Using
      religion and spirituality as resources in coping may be specifically prevalent in
      patients with cancer considering the potentially life-threatening nature of the
      illness. Religious/spiritual coping may also serve multiple functions in long
      term adjustment to cancer such as maintaining self-esteem, providing a sense of
      meaning and purpose, giving emotional comfort and providing a sense of hope.
      Seventeen papers met the inclusion criteria of which seven found some evidence
      for the beneficial effect of religious coping, but one of these also found
      religious coping to be detrimental in a sub-sample of their population. A further
      three studies found religious coping to be harmful and seven found non
      significant results. However, many studies suffered from serious methodological
      problems, especially in the manner in which religious coping was conceptualised
      and measured. The studies also failed to control for possible influential
      variables such as stage of illness and perceived social support. Due to this, any
      firm conclusions about the possible beneficial or harmful effects of religious
      coping with cancer is lacking. These problems are discussed and suggestions for
      future studies are made.

PMID- 16427174
TI  - Sleep, health and the dynamics of biomedicine.
AB  - This paper examines the relationship between sleep and health from a sociological
      perspective. Two interrelated case studies are explored: the emergence of the
      category of obstructive sleep apnoea syndrome, nowadays the most commonly
      diagnosed sleep disorder, and the shaping of continuous positive airway pressure,
      the therapy of choice for sleep apnoea in contemporary clinical practice. Data
      were gathered through a historical review of relevant literature and observation
      of online patient discussion groups. The examples analysed show that although the
      social organisation of the relationship between sleep and health can be
      understood as a process of medicalisation, this framework is insufficient for
      understanding how researchers, clinicians and patients interactively deploy the
      knowledge, techniques and technologies through which different 'sleep problems'
      are understood and managed. By exploring the generative aspects of those
      processes of contestation and divergence within biomedicine it is possible to
      initiate a re-evaluation of the role of patients' identity in the transformation
      of sleep medicine and associated health technologies.

PMID- 16427175
TI  - Study design in fMRI: basic principles.
AB  - There is a wide range of functional magnetic resonance imaging (fMRI) study
      designs available for the neuroscientist who wants to investigate cognition. In
      this manuscript we review some aspects of fMRI study design, including cognitive
      comparison strategies (factorial, parametric designs), and stimulus presentation
      possibilities (block, event-related, rapid event-related, mixed, and self-driven
      experiment designs) along with technical aspects, such as limitations of signal
      to noise ratio, spatial, and temporal resolution. We also discuss methods to deal
      with cases where scanning parameters become the limiting factor (parallel
      acquisitions, variable jittered designs, scanner acoustic noise strategies).

PMID- 16427176
TI  - Symptoms of depression as possible markers of bipolar II disorder.
AB  - Underdiagnosis and misdiagnosis of bipolar-II disorder (BP-II) as a major
      depressive disorder (MDD) are frequently reported. The study aim was to find
      which symptoms of depression could be possible cross-sectional markers of BP-II,
      in order to reduce underdiagnosing BP-II. METHODS: Consecutive 379 BP-II and 271
      MDD major depressive episode (MDE) outpatients were interviewed with the
      Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the
      Family History Screen, by a senior psychiatrist in a private practice. Inside-MDE
      hypomanic symptoms (elevated mood and increased self-esteem always absent by
      definition) were systematically assessed. Mixed depression was defined as an MDE
      plus 3 or more inside-MDE hypomanic symptoms, a definition validated by Akiskal
      and Benazzi. RESULTS: The MDE symptoms significantly more common in BP-II versus
      MDD were weight gain, increased eating, hypersomnia, psychomotor agitation,
      worthlessness, and diminished ability to concentrate. The inside-MDE hypomanic
      symptoms significantly more common in BP-II were distractibility, racing/crowded
      thoughts, irritability, psychomotor agitation, more talkativeness, increased
      risky and goal-directed activities. Multiple logistic regression showed that
      hypersomnia, racing/crowded thoughts, irritability, and psychomotor agitation
      were independent predictors of BP-II. Irritability had the most balanced
      combination of sensitivity and specificity predicting BP-II. Psychomotor
      agitation had the highest specificity but the lowest sensitivity. Racing/crowded
      thoughts had the highest sensitivity but the lowest specificity. These symptoms
      had a similar positive predictive value (PPV) for BP-II, which was around 70%
      (PPV is more clinically useful than sensitivity and specificity), which in turn
      was similar to the PPV of mixed depression and atypical depression (two
      diagnostic clinical markers of BP-II). All possible combinations of these
      symptoms had a PPV similar to that of the individual symptoms. The validity as BP
      II markers of these symptoms was supported by a significant association with
      bipolar family history. CONCLUSIONS: Hypersomnia, racing/crowded thoughts,
      irritability, and psychomotor agitation may be useful, cross-sectional markers of
      BP-II. Finding these symptoms in depression should lead the clinician to careful
      probing for history of hypomania, which should reduce the BP-II misdiagnosed as
      MDD. Results may also have treatment impacts, as antidepressants used alone
      (i.e., no concurrent mood stabilising agent) in BP-II depression misdiagnosed as
      MDD may increase cycling.

PMID- 16427177
TI  - Comparative acute and combinative toxicity of aflatoxin B1 and fumonisin B1 in
      animals and human cells.
AB  - Aflatoxin B(1) (AFB(1)) and fumonisin B(1) (FB(1)) are important food-borne
      mycotoxins. The co-contamination of food stuffs with these two mycotoxins is well
      known and has been possibly implicated in the development of human hepatocellular
      carcinoma in high risk regions around the world. In this study the acute and
      combinative toxicity of AFB(1) and FB(1) were tested in F-344 rats, mosquitofish
      (Gambusia affinis), immortalized human hepatoma cells (HepG2) and human bronchial
      epithelial cells (BEAS-2B). Preliminary experiments were conducted in order to
      assess the acute toxicity and obtain LD(50), LC(50) and IC(50) values for
      individual toxins in each model, respectively. This was followed by testing
      combinations of AFB(1) and FB(1) to obtain LD(50), LC(50) and IC(50) values for
      the combination in each model. All models demonstrated a significant dose
      response in relation to toxin treatment. The potency of the mixture was gauged
      through the determination of the interaction index metric. Results of this study
      demonstrate that these two toxins interacted to produce alterations in the toxic
      responses with a strong additive interaction noted in the cases of F344 rats and
      mosquitofish. It can be gathered that this combination may pose a significant
      threat to public health and further research needs to be completed addressing
      alterations in metabolism and detoxification that may influence the toxic
      manifestations in combination. These results will provide foundational knowledge
      for future studies on long-term combinative toxic and health effects of these
      mycotoxins.

PMID- 16427178
TI  - Physalis angulata induced G2/M phase arrest in human breast cancer cells.
AB  - Physalis angulata (PA) is employed in herbal medicine around the world. It is
      used to treat diabetes, hepatitis, asthma and malaria in Taiwan. We have
      evaluated PA as a cancer chemopreventive agent in vitro by studying the role of
      PA in regulation of proliferation, cell cycle and apoptosis in human breast
      cancer cell lines. PA inhibited cell proliferation and induced G2/M arrest and
      apoptosis in human breast cancer MAD-MB 231 and MCF-7 cell lines. In this study,
      under treatment with various concentrations of PA in MDA-MB 231 cell line, we
      checked mRNA levels for cyclin A and cyclin B1 and the protein levels of cyclin A
      and cyclin B1, Cdc2 (cyclin-dependent kinases), p21(waf1/cip1) and P27(Kip1)
      (cyclin-dependent kinase inhibitors), Cdc25C, Chk2 and Wee1 kinase (cyclin
      dependent kinase relative factors) in cell cycle G2/M phase. From those results,
      we determined that PA arrests MDA-MB 231 cells at the G2/M phase by (i)
      inhibiting synthesis or stability of mRNA and their downstream protein levels of
      cyclin A and cyclin B1, (ii) increasing p21(waf1/cip1) and P27(kip1) levels,
      (iii) increasing Chk2, thus causing an increase in Cdc25C
      phosphorylation/inactivation and inducing a decrease in Cdc2 levels and an
      increase in Wee1 level. According to the results obtained, PA appears to possess
      anticarcinogenic properties; these results suggest that the effect of PA on the
      levels of phosphorylated/inactivated Cdc25C are mediated by Chk2 activation, at
      least in part, via p21(waf1/cip1) and P27(kip1) cyclin-dependent kinase
      inhibitors pathway to arrest cells at G2/M phase in breast cancer carcinoma
      cells.

PMID- 16427179
TI  - Depletion of adenine nucleotide translocator protein in heart mitochondria from
      doxorubicin-treated rats--relevance for mitochondrial dysfunction.
AB  - Doxorubicin (DOX) is a highly effective treatment for several forms of cancer.
      However, DOX induces a cumulative and dose-dependent cardiomyopathy that has been
      ascribed to redox-cycling of the molecule on the mitochondrial complex I
      generating in the process increased oxidative stress. Mitochondrial dysfunction,
      including induction of the mitochondrial permeability transition (MPT) and
      inhibition of mitochondrial respiration have been implicated as major
      determinants in the pathogenesis of DOX cardiotoxicity. The adenine nucleotide
      translocator (ANT) has been suggested to be a principal component of the MPT pore
      and a possible target for DOX-induced cardiotoxicity. Nonetheless, no definitive
      evidence has been presented showing that altered ANT activity is due to decreased
      amount of the protein. By using carboxyatractyloside as a specific modulator of
      ANT activity and Western blotting, we observed that following DOX treatment in
      rats: (1) the amount of "functional ANT" that contributes to cardiac
      mitochondrial respiration with different substrates is reduced, (2) titrations
      with carboxyatracyloside revealed a lower threshold for MPT induction and most
      importantly, (3) a specific decrease in the amount of the ANT protein. This study
      identifies the ANT as one important target for DOX-induced cardiac toxicity and
      correlates the decrease in ANT protein concentration with inhibition of
      mitochondrial respiration and increased ability to form or at least regulate MPT
      pores.

PMID- 16427180
TI  - Activity and gene expression profile of certain antioxidant enzymes to
      microcystin-LR induced oxidative stress in mice.
AB  - Microcystins are cyclic heptapeptide toxins produced by certain strains of
      Microcystis aeruginosa and microcystin-LR (MC-LR) is the most toxic among the 70
      variants isolated so far. These toxins have been implicated in both human and
      livestock mortality. In the present study we investigated the microcystin-LR
      induced oxidative stress in mice in terms of its effect on activity and gene
      expression profile of certain antioxidant enzymes and expression of heat shock
      protein-70 (HSP-70). Mice were treated with 0.5 LD50 (38.31 microg/kg) and 1 LD50
      (76.62 microg/kg) and the biochemical variables were determined at 1, 3, 7 days
      and 15, 30, 60 and 120 min post-exposure for 0.5 and 1 LD50 dose, respectively. A
      significant time-dependent increase in HSP-70 expression over control was
      observed at 1 LD50 dose. The toxin induced significant increase in liver body
      weight index, hepatic lipid peroxidation and depletion of GSH levels at 1 LD50
      compared to control group. There was significant decrease in the activity of
      antioxidant enzymes glutathione peroxidase (GPX), superoxide dismutase (SOD),
      catalase (CAT), glutathione reductase (GR) and glutathione-S-transferase (GST) at
      1 LD50. Except catalase, there was no effect on other antioxidant enzymes at 0.5
      LD50 dose. In contrast to activity of antioxidant enzymes the gene expression
      profile did not show any significant difference compared to control at 1 LD50. GR
      showed significant decrease in expression at 1, 3 and 7 days in animals dosed
      with 0.5 LD50 MC-LR. The results of our in vivo study clearly show the oxidative
      stress induced by MC-LR, and a correlation with activity and regulation at gene
      expression level of antioxidant enzymes.

PMID- 16427181
TI  - Effect of in vivo phenol or hydroquinone exposure on events related to neutrophil
      delivery during an inflammatory response.
AB  - Phenol (PHE) and hydroquinone (HQ) are metabolites of benzene that affect
      leukocytes after solvent intoxication. Hence, we investigated the effects of PHE
      or HQ exposure on neutrophil mobilization during an inflammatory response. Male
      Wistar rats received intraperitoneal injections of PHE, HQ or vehicle only and
      assays were performed 24 h after the last dose. Quantifications of bone marrow or
      circulating leukocytes showed that only HQ exposure induced neutrophilia,
      probably due to the accelerated mobilization from the bone marrow compartment,
      since reduced numbers of segmented cells in the last phase of maturation were
      detected there. Intravital microscopy showed that circulating leukocytes of HQ
      exposed rats increased their rolling behavior and adherence to the mesenteric
      postcapillary venule wall in vivo. The enhanced leukocyte-endothelium interaction
      was not dependent on microvascular reactivity or perivascular mast cell
      degranulation. Instead, it was the result of neutrophil activation, demonstrated
      by a decrease in L-selectin and an increase in beta2 integrin expression on
      neutrophil membranes. This pattern of neutrophil activation may have contributed
      to the higher number of neutrophils in the subcutaneous inflammatory response of
      HQ-exposed rats after oyster glycogen injection. Taken together, our results
      indicate that HQ exposure alters neutrophil mobilization, which results in an
      exacerbated response after an injury. Although PHE is endogenously metabolized to
      HQ, PHE exposure only induced an increment in rolling behavior, which was not
      sufficient to alter the inflammatory response.

PMID- 16427182
TI  - Compressive strength recovery by composite onlays in primary teeth. Substrate
      treatment and luting agent effects.
AB  - OBJECTIVES: To evaluate 1% NaOCl treatment and two resin luting agent effects on
      compressive strength recovery in composite onlays on primary teeth and to analyze
      the fractures type. METHODS: Forty sound primary molars crowns were prepared in
      the standard machine and randomly divided into four groups (n=10): G1 (1% NaOCl/
      30 min+EnForce); G2 (without 1% NaOCl EnForce); G3 (1% NaOCl/ 30 min+Rely X); G4
      (without 1% NaOCl+Rely X). The onlays were made using Z250 composite on plaster
      models. Ten sound teeth were used as control group (CG). All groups were
      submitted to compression mechanic test in a universal test machine INSTRON at
      1mm/min cross-head speed. After that, the data (kgf) were submitted to ANOVA test
      (alpha=0.05). Finally, the fracture types were classified in a crescent scale (1
      5) related with severity degree and submitted to Fisher's Exact Test (p<0.05).
      Scanning electronic microscope analysis was done in order to illustrate the
      fractures sites. RESULTS: The values of compressive strength of experimental
      groups did not differ each others neither from control group (p>0.05). The
      results from fracture type showed that types 5 and 4 fractures (most severe)
      present the highest percentage to experimental groups. Conversely, the CG showed
      higher percentage of fracture types 2 and 3. CONCLUSIONS: This research found
      that the composite onlays recovered the compressive strength compared to sound
      teeth, regardless of the substrate treatment and cement agent used. Nevertheless,
      no group showed similar type of fractures to CG, which had more frequency of less
      severe fracture types.

PMID- 16427183
TI  - The antioxidant glutathione peroxidase family and spermatozoa: a complex story.
AB  - Oxidative damage is one threat spermatozoa have to face during epididymal
      maturation and storage. However, it is clear that reactive oxygen species (ROS)
      are also central for sperm physiology in processes such as sperm maturation and
      capacitation. It is therefore essential that there exists around sperm cells a
      fine balance between ROS production and recycling. To do so, sperm cells and
      epididymal epithelial cells rely on common enzymatic ROS scavengers such as
      superoxide dismutase (SOD), glutathione peroxidases (GPX) and catalase (CAT) as
      well as more specific types such as indoleamine dioxygenase (IDO). Among the
      catalytic triad (SOD/GPX/CAT), the glutathione peroxidase protein family occupies
      a peculiar position, since several GPX have been found to be present on and
      around epididymal transiting sperm cells. Here, we will review our present
      knowledge regarding GPX expression, presence and putative role(s) within the
      epididymis and on spermatozoa. Taking into account our recent findings regarding
      the epididymal expression of indoleamine dioxygenase in mouse we will also
      discuss how we think this superoxide anion recycling enzyme completes the complex
      ROS generation/recycling balance in this organ.

PMID- 16427184
TI  - Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast
      carcinoma: possible regulator of insitu steroidogenesis.
AB  - Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor.
      We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1
      immunoreactivity was detected in 43% of the invasive ductal carcinoma. It was
      negatively correlated with clinical stage, histological grade and HER2 status,
      and positively associated with sex-steroid receptors, steroidogenic acute
      regulatory protein, P450 side-chain cleavage, and 3beta-hydroxysteroid
      dehydrogenase. LRH-1 immunoreactivity was also detected in 28% of the ductal
      carcinoma in situ. These results suggest that LRH-1 is frequently detected in
      breast carcinoma tissues, and plays important roles including the regulation of
      in situ steroidogenesis.

PMID- 16427185
TI  - COX-2 expression in pseudomyxoma peritonei.
AB  - COX-2 expression was studied using an immunohistochemical method in 75 patients
      with pseudomyxoma peritonei (PMP). Twenty-five patients presented with
      disseminated peritoneal adenomucinosis (DPAM) and 50 with peritoneal mucinous
      carcinomatosis (PMCA). COX-2 was expressed in neoplastic mucinous epithelium of
      30 cases (40%): 20 in PMCA (40%), 10 in DPAM (40%). Weak COX-2 expression was
      also noted in four of five patients with appendiceal mucinous neoplasms without
      peritoneal dissemination. In addition, COX-2 was detected in stromal,
      endothelial, inflammatory cells and reactive mesothelium. This preliminary
      information indicates a potential for the use of COX-2 inhibitors in patients
      with PMP.

PMID- 16427186
TI  - Apoptosis of HL-60 cells induced by extracts from Narcissus tazetta var.
      chinensis.
AB  - Narcissus tazetta var. chinensis is one member of the Amaryllidaceae family. We
      found that extracts from N. tazetta var. chinensis (ENT) strongly decreased the
      survival rate of the following tumor cell lines: HL-60, K562, KT1/A3, and A3R.
      The cytotoxic effects of ENT on non-cancer cells lines (NHBE and NIH3T3) were
      smaller than on leukemia cell lines. AO/EB staining and flow cytometry assays
      showed that ENT induced HL-60 cell apoptosis. Furthermore, the release of
      cytochrome c and the increase of caspase-8, -9, and -3 activities were tested
      after HL-60 cells were treated with ENT, which indicated that the mitochondrial
      pathway and cell death receptor pathway were both involved in the apoptosis
      signal pathways induced by ENT. Upregulation of Bax showed that the Bcl-2 family
      was involved in the control of apoptosis. Our results suggest that apoptosis
      activity can be mediated by ENT in HL-60 cells.

PMID- 16427187
TI  - Expression of Lea in gastric cancer cell lines depends on FUT3 expression
      regulated by promoter methylation.
AB  - Aberrant expression of Lewis antigens has been demonstrated in gastric lesions,
      namely gastritis, intestinal metaplasia (IM) and gastric carcinoma (GC), and can
      be partly due to overexpression of the Lewis (FUT3) enzyme. Our aim was to
      evaluate the role of promoter methylation in FUT3 and Le(a) expression in gastric
      carcinoma cell lines. MKN45 cell line showed low amounts of Le(a), in the absence
      of FUT3; GP220 expressed high levels of Le(a) and FUT3. After 5aza
      2'deoxycytidine MKN45 showed increased levels of FUT3 and Le(a), by
      immunohistochemistry and Real-Time PCR, whereas GP220 showed an increase in FUT3
      without increase of Le(a). Enzyme activity assays confirmed an increase in alpha
      1,4 fucosyltransferase activity in both cell lines by 5aza-2'deoxycytidine.
      Luciferase reporter gene assays, using methylated and unmethylated deletion
      constructs of FUT3 promoter, showed that FUT3 expression is regulated by
      methylation. Summing up, we showed that FUT3 overexpression in gastric cells
      depends upon promoter hypomethylation and that FUT3 is responsible for
      overexpression of Le(a) in gastric cells, in vitro. FUT3, Lea, Methylation.

PMID- 16427189
TI  - Hypoxia confers protection against apoptosis via PI3K/Akt and ERK pathways in
      lung cancer cells.
AB  - Hypoxia confers protection against apoptosis in cancer cells, and this hypoxia
      induced resistance to apoptosis has been suggested to be associated with genetic
      and adaptive changes. However, it is not clear whether survival signals, such as
      the PI3K/Akt and ERK pathways are involved. We investigated the roles of these
      pathways in hypoxia-induced protection against apoptosis in lung cancer cells.
      Treatment of cells with either ultraviolet (UV) or etoposide induced apoptosis
      time-dependently in A549 and NCI-H157 cells. However, though hypoxia alone
      neither induced apoptosis nor reduced cell survival, it suppressed the apoptosis
      induced by UV or etoposide. Moreover, hypoxia activated the PI3K/Akt and ERK
      pathways, and blocking the activation of either pathway reversed resistance to UV
      and etoposide-induced apoptosis in response to hypoxia. These results suggest
      that hypoxia confers resistance to UV- or etoposide-mediated apoptosis in lung
      cancer cells via the activations of the PI3K/Akt and the ERK pathways.

PMID- 16427188
TI  - Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0
      melanoma cells.
AB  - In the current work we investigated for the first time the biochemical basis of 4
      hydroxyanisole (4-HA) induced toxicity in B16-F0 melanoma cells. It was found
      that dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depleting
      agent, increased 4-HA induced toxicity towards B16-F0 cells whereas
      dithiothreitol, a thiol containing agent, and ascorbic acid (AA), a reducing
      agent, largely prevented 4-HA toxicity. TEMPOL and pyrogallol, free radical
      scavengers, did not significantly prevent 4-HA toxicity towards B16-F0 cells.
      GSH>AA>NADH prevented the o-quinone formation when 4-HA was metabolized by
      tyrosinase/O(2). 4-HA metabolism by horseradish peroxidase/H(2)O(2) was prevented
      more effectively by AA than NADH>GSH. We therefore concluded that quinone
      formation was the major pathway for 4-HA induced toxicity in B16-F0 melanoma
      cells whereas free radical formation played a negligible role in the 4-HA induced
      toxicity.

PMID- 16427190
TI  - Assessment of environmental radon hazard using human respiratory tract models.
AB  - Radon is a natural radioactive gas derived from geological materials. It has been
      estimated that about half of the total effective dose received by human beings
      from all sources of ionizing radiation is attributed to 222Rn and its short-lived
      progeny. In this paper, the use of human respiratory tract models to assess the
      health hazard from environmental radon is reviewed. A short history of dosimetric
      models for the human respiratory tract from the International Commission on
      Radiological Protection (ICRP) is first presented. The most important features of
      the newest model published by ICRP in 1994 (as ICRP Publication 66) are then
      described, including the morphometric model, physiological parameters, radiation
      biology, deposition of aerosols, clearance model and dose weighting. Comparison
      between different morphometric models and comparison between different deposition
      models are then given. Finally, the significance of various parameters in the
      lung model is discussed, including aerosol parameters, subject related
      parameters, target and cell related parameters, and parameters that define the
      absorption of radon from the lungs to blood. Dosimetric calculations gave a dose
      conversion coefficient of 15 mSv/WLM, which is higher than the value 5 mSv/WLM
      derived from epidemiological studies. ICRP stated that dosimetric models should
      only be used for comparison of doses in the human lungs resulted from different
      exposure conditions.

PMID- 16427191
TI  - Technologies for laboratory generation of dust from geological materials.
AB  - Dusts generated in the laboratory from soils and sediments are used to evaluate
      the emission intensities, composition, and environmental and health impacts of
      mineral aerosols. Laboratory dust generation is also utilized in other
      disciplines including process control and occupational hygiene in manufacturing,
      inhalation toxicology, environmental health and epidemiology, and pharmaceutics.
      Many widely available and/or easily obtainable laboratory or commercial
      appliances can be used to generate mineral aerosols, and several distinct classes
      of dust generators (fluidization devices, dustfall chambers, rotating
      drums/tubes) are used for geological particulate studies. Dozens of different
      devices designed to create dust from soils and sediments under controlled
      laboratory conditions are documented and described in this paper. When choosing a
      specific instrument, investigators must consider some important caveats:
      different classes of dust generators characterize different properties (complete
      collection of a small puff of aerosol versus sampling of a representative portion
      of a large aerosol cloud) and physical processes (resuspension of deposited dust
      versus in situ production of dust). The quantity "dustiness" has been used in
      industrial and environmental health research; though it has been quantified in
      different ways by different investigators, it should also be applicable to
      studies of geological aerosol production. Using standardized dust-production
      devices and definitions of dustiness will improve comparisons between
      laboratories and instruments: lessons learned from other disciplines can be used
      to improve laboratory research on the generation of atmospheric dusts from
      geological sources.

PMID- 16427192
TI  - Electrochemical oxidation of phenol in a parallel plate reactor using ruthenium
      mixed metal oxide electrode.
AB  - In this study, electrochemical oxidation of phenol was carried out in a parallel
      plate reactor using ruthenium mixed metal oxide electrode. The effects of initial
      pH, temperature, supporting electrolyte concentration, current density, flow rate
      and initial phenol concentration on the removal efficiency were investigated.
      Model wastewater prepared with distilled water and phenol, was recirculated to
      the electrochemical reactor by a peristaltic pump. Sodium sulfate was used as
      supporting electrolyte. The Microtox bioassay was also used to measure the
      toxicity of the model wastewater during the study. As a result of the study,
      removal efficiency of 99.7% and 88.9% were achieved for the initial phenol
      concentration of 200 mg/L and chemical oxygen demand (COD) of 480 mg/L,
      respectively. In the same study, specific energy consumption of 1.88 k Wh/g
      phenol removed and, mass transfer coefficient of 8.62 x 10(-6)m/s were reached at
      the current density of 15 mA/cm(2). Electrochemical oxygen demand (EOD), which
      can be defined as the amount of electrochemically formed oxygen used for the
      oxidation of organic pollutants, was 2.13 g O(2)/g phenol. Electrochemical
      oxidation of petroleum refinery wastewater was also studied at the optimum
      experimental conditions obtained. Phenol removal of 94.5% and COD removal of
      70.1% were reached at the current density of 20 mA/cm(2) for the petroleum
      refinery wastewater.

PMID- 16427193
TI  - Dust dispersal and Pb enrichment at the rare-metal Orlovka-Spokoinoe mining and
      ore processing site: insights from REE patterns and elemental ratios.
AB  - Different geological, technogenic and environmental samples from the Orlovka
      Spokoinoe Ta-Nb-Sn-W mining site and ore processing complex in Eastern
      Transbaikalia (Russia), were analysed for Pb, Y, Zr, Hf and rare earth elements
      (REE) to assess the effect of dust and metal dispersal on the environment within
      the Orlovka-Spokoinoe mining site. Potential source material analysed included
      ore-bearing and barren granites, host rocks, tailing pond sediments, and ore
      concentrates. Lichens and birch leaves were used as receptor samples. The REE
      enrichment relative to chondrite, the extent of the Eu anomalies, the enrichments
      of heavy REE (HREE), and Zr/Hf and Yb/Y ratios suggest that tailings, barren
      granites, and metasedimentary host rocks are the main sources of dust in the
      studied mining environment. In addition, calculated lead enrichment (relative to
      host rocks) suggests that the environment is polluted with Pb. Our results
      clearly demonstrate the potential of REE patterns and elemental ratios as a
      reliable technique to trace dust and metals sources and dispersal within a
      confined mining area offering a new tool for environmental assessment studies.

PMID- 16427194
TI  - Dispersion modeling of PM10 released during decontamination activities.
AB  - The decontamination and decommissioning of radioactively contaminated structures
      and facilities, volume reduction of massive metal structures, and demolition of
      large concrete structures, result in release of large quantities of contaminants
      that become airborne and thus could be inhaled by workers and population living
      in the neighborhood. In order to provide adequate protection to the workers,
      adequate monitoring of the airborne particulates and proper models that predict
      the dispersion of the airborne contaminants are needed. The dispersion model will
      enable development of decision tools on the extent of decontamination that needs
      to be performed prior to dismantlement and the optimization of personal
      protective equipment requirements during D&D operations. The Gaussian plume
      dispersion model is used in this study to predict the dispersion of airborne
      particulate PM10 (dp<10 microm) released from: (1) a 35 m height contaminant
      plant where the plume is affected by the presence of 36 buildings around the
      emission source, (2) a building during decontamination and removal of process
      equipment and (3) demolition of contaminant building. The potential impact of
      PM10 on 180 receptors located at five downwind distances between 0.1 and 20 km
      around the emission source was performed. A short-term (1-48 h) prediction of
      average concentration of PM10 from point and area sources on receptors located at
      ground level was obtained. The concentrations of PM10 over 24h time period were
      compared to the U.S. air quality standards. The results obtained in the course of
      this study are used to predict the inhalation exposures of workers and population
      living in neighborhood.

PMID- 16427195
TI  - Mesolimbic dopaminergic mechanisms and pain control.

PMID- 16427196
TI  - Peripheral inflammation modifies the effect of intrathecal IL-1beta on spinal
      PGE2 production mainly through cyclooxygenase-2 activity. A spinal microdialysis
      study in freely moving rats.
AB  - Acute inflammation induces upregulation of IL-1beta both at the site of the
      peripheral inflammation and in the cerebrospinal fluid (CSF). The central
      increase of IL-1beta mainly contributes to the development of hypersensitivity.
      However, the spinal mechanisms for the effects of IL-1beta in nociceptive
      transmission are incompletely understood. It is also unknown whether previous
      sensitization changes IL-1beta activity. We therefore investigated the dose
      effect relationship of intrathecal (i.t.) IL-1beta on spinal PGE(2) production in
      the absence and presence of peripheral formalin inflammation with spinal
      microdialysis in freely moving rats. The possible involvement of cyclooxygenase
      (COX) isoforms in the IL-1beta-mediated spinal PGE(2) production on the
      background of peripheral formalin inflammation was further evaluated with the
      selective COX-1 and COX-2 inhibitors. We found that the i.t. administration of IL
      1beta, with doses of 1, 2, 8, or 16 ng, increased PGE(2) levels in CSF in a dose
      related fashion. This IL-1beta-evoked PGE(2) release occurred within 30min after
      IL-1beta administration, peaked at 30-60 min interval, and returned gradually to
      the baseline level within 4h. Peripheral formalin inflammation in the paw induced
      a more prolonged effect of spinal IL-1beta with larger PGE(2) releases in the CSF
      compared with the non-inflammatory state, suggesting that peripheral inflammation
      enhances central sensitization. The COX-2 inhibitor SC58236 (15 mg/kg) reduced
      the IL-1beta-mediated PGE(2) increase in CSF by 86% while the COX-1 inhibitor
      SC58560 (15 mg/kg) had less effect (28%). Our study suggests that mainly the COX
      2 enzyme mediates the IL-1beta-induced increase in spinal PGE(2) in the presence
      of peripheral formalin inflammation.

PMID- 16427197
TI  - Methadone maintenance patients are cross-tolerant to the antinociceptive effects
      of very high plasma morphine concentrations.
AB  - Opioid dependent patients require higher than normal doses of opioid analgesics.
      However, this regimen has not been formally tested. This study utilised a double
      blind placebo-controlled design to examine antinociceptive responses to saline
      and pseudo-steady-state plasma morphine concentrations (173+/-11 (mean+/-SEM),
      range 106-305 ng/ml) in 18 methadone participants in three stable, once daily
      methadone dose ranges 11-45 mg (n=6), 46-80 mg (n=6), 81-115 mg (n=6) and 10
      controls. Testing commenced approximately 20 h after the maintenance dose with
      the next dose given 1h after morphine cessation. Nociceptive stimuli (cold
      pressor (seconds) and electrical stimulation (volts)) were used to measure pain
      detection threshold and pain tolerance. Blood samples were analysed by HPLC for
      plasma morphine and R-(-)-methadone concentrations. Methadone participants were
      hyperalgesic to cold pressor pain. High plasma morphine concentrations failed to
      significantly change cold pressor and electrical stimulation pain tolerance for
      methadone patients, but in controls, morphine significantly (P<0.05) increased
      mean pain tolerance to cold pressor by 59+/-29% (range -17% to 311%) and
      electrical stimulation by 19+/-6% (range 0% to 58%). Morphine significantly
      (P<0.05) decreased respiration rates by 12+/-3% (range -29% to 8%) in methadone
      subjects. On saline days, rising methadone concentrations significantly (P<0.01)
      increased cold pressor pain detection threshold by 32+/-6% (range 1-81%) and cold
      pressor pain tolerance by 23+/-6% (range -32% to 56%). Methadone maintained
      patients are hyperalgesic and cross-tolerant to the antinociceptive effects of
      very high plasma morphine concentrations. While even higher morphine doses may
      achieve some pain relief, this may be at the cost of unacceptable respiratory
      depression.

PMID- 16427198
TI  - Distinct forebrain activity patterns during deep versus superficial pain.
AB  - All pain is unpleasant, but different perceptual and emotional qualities are
      characteristic of pain originating in different structures. Pain of superficial
      (cutaneous) origin usually is sharp and restricted, whereas pain of deep origin
      (muscle/viscera) generally is dull and diffuse. Despite the differences it has
      been suggested previously that all pain is mediated by an invariant set
      ("neuromatrix") of brain structures. However, we report here, using functional
      magnetic resonance imaging (fMRI), that striking regional differences in brain
      activation patterns were the rule. Signal differences were found in regions
      implicated in emotion (perigenual cingulate cortex), stimulus localization and
      intensity (somatosensory cortex) and motor control (motor cortex, cingulate motor
      area). Further, most fMRI signal changes matched perceived changes in pain
      intensity. These findings clearly indicate that distinct neural activity patterns
      in distinct sets of brain structures are evoked by pain originating from
      different tissues of the body. Further, we suggest that these differences
      underlie the different perceptual and emotional reactions evoked by deep versus
      superficial pain.

PMID- 16427199
TI  - Pathologic alterations of cutaneous innervation and vasculature in affected limbs
      from patients with complex regional pain syndrome.
AB  - Complex regional pain syndromes (CRPS, type I and type II) are devastating
      conditions that can occur following soft tissue (CRPS type I) or nerve (CRPS type
      II) injury. CRPS type I, also known as reflex sympathetic dystrophy, presents in
      patients lacking a well-defined nerve lesion, and has been questioned as to
      whether or not it is a true neuropathic condition with an organic basis. As
      described here, glabrous and hairy skin samples from the amputated upper and
      lower extremity from two CRPS type I diagnosed patients were processed for double
      label immunofluorescence using a battery of antibodies directed against neural
      related proteins and mediators of nociceptive sensory function. In CRPS affected
      skin, several neuropathologic alterations were detected, including: (1) the
      presence of numerous abnormal thin caliber NF-positive/MBP-negative axons
      innervating hair follicles; (2) a decrease in epidermal, sweat gland, and
      vascular innervation; (3) a loss of CGRP expression on remaining innervation to
      vasculature and sweat glands; (4) an inappropriate expression of NPY on
      innervation to superficial arterioles and sweat glands; and (5) a loss of
      vascular endothelial integrity and extraordinary vascular hypertrophy. The
      results are evidence of widespread cutaneous neuropathologic changes.
      Importantly, in these CRPS type I patients, the myriad of clinical symptoms
      observed had detectable neuropathologic correlates.

PMID- 16427200
TI  - Laser guns and hot plates revisited.

PMID- 16427201
TI  - The detection of anthelmintic resistance in nematodes of veterinary importance.
AB  - Before revised World Association for the Advancement of Veterinary Parasitology
      (WAAVP) guidelines on the detection of anthelmintic resistance can be produced,
      validation of modified and new methods is required in laboratories in different
      parts of the world. There is a great need for improved methods of detection of
      anthelmintic resistance particularly for the detection of macrocyclic lactone
      resistance and for the detection of resistant nematodes in cattle. Therefore,
      revised and new methods are provided here for the detection of anthelmintic
      resistance in nematodes of ruminants, horses and pigs as a basis for discussion
      and with the purpose that they are evaluated internationally to establish whether
      they could in the future be recommended by the WAAVP. The interpretation of the
      faecal egg count reduction test has been modified and suggestions given on its
      use with persistent anthelmintics and continuous release devices. An egg hatch
      test for benzimidazole (BZ) resistance is described. A microagar larval
      development test for the detection of benzimidazole and levamisole resistance
      provides third stage larvae for the identification of resistant worms. The
      sensitivity of these two tests can be increased by using discriminating doses
      rather than LD(50) values. Details are given of a PCR based test for the analysis
      of benzimidazole resistance in strongyles of sheep and goats, horses and cattle.
      Although promising for ruminant trichostrongyles, quantitative determination of
      gene frequency using real time PCR requires further development before PCR tests
      will be used in the field. Apart from faecal egg count reduction tests there are
      currently no satisfactory tests for macrocylic lactone resistance despite the
      great importance of this subject. Except for treatment and slaughter trials there
      are no validated tests for fasciolicide resistance or for the detection of
      resistance in cestodes.

PMID- 16427202
TI  - Efficacy of short-term feeding of sulla (Hedysarum coronarium) to young goats
      against a mixed burden of gastrointestinal nematodes.
AB  - The aim was to investigate the efficacy of feeding sulla to young goats (<6
      months of age) against a naturally acquired infection of gastrointestinal
      nematodes. Eleven goats were removed from the field, housed and were randomly
      divided into two treatment groups. Group 1 (n = 5) was fed a diet comprising
      lucerne-based pellets and aged hay. Group 2 (n = 6) were fed a diet of only sulla
      offered ad lib. The sulla contained 2.6% free condensed tannins (CT), 1.8%
      protein-bound CT and 0.1% fibre-bound CT. Goats in Gp 2 ate the sulla very
      readily from the first day. The goats were fed these diets for 10 days, then
      killed and total worm counts obtained. The arithmetic mean worm counts (in
      parentheses) for Gp 1 and Gp 2, respectively, were Teladorsagia circumcincta
      (5792, 5690), Trichostrongylus colubriformis (272, 262), T. vitrinus (1060, 1804)
      and Trichuris spp. (32, 30). There were no significant differences (p > 0.05)
      between any of these treatments. Short-term feeding of sulla had no effect on
      mixed burdens of gastrointestinal nematodes.

PMID- 16427203
TI  - PCR diagnosis of Fasciola hepatica in field-collected Lymnaea columella and
      Lymnaea viatrix snails.
AB  - Fasciolosis, caused by the trematode Fasciola hepatica, is a zoonosis of economic
      importance in livestock that is emerging as a chronic disease in humans. The
      intermediate hosts are lymnaeid snails, in which diagnosis of infection is
      traditionally based on cercarial shedding, tissue sectioning and crushing. We
      developed a PCR assay for the sensitive and specific detection of F. hepatica in
      field-collected Lymnaea sp. snails. A primer pair was designed to amplify a 405
      bp fragment of the cytochrome c oxidase subunit 1 gene of F. hepatica. The PCR
      assay showed a limit of detection of 10 pg of genomic F. hepatica DNA. No cross
      reactions were observed with samples from other related trematode species or from
      the snail hosts Lymnaea columella and Lymnaea viatrix. DNA sequencing of the
      amplicon showed 100% homology with F. hepatica, and 75-89% homology with other
      trematodes on regions that did not include the entire set of primers. Two samples
      from Argentina were analysed. For snails in sample 1 (n = 240), identified as L.
      columella, the infection rate was 17.5 and 51.3% by direct examination and PCR,
      respectively. For snails in sample 2 (n = 34), identified as L. viatrix, the
      infection rate was 2.9 and 61.8% by direct examination and PCR, respectively.
      Differences in infection rates between these diagnosis methods were significant
      for both samples. Our PCR technique showed to be effective for detecting specific
      F. hepatica infections of low intensity in the intermediate host, and hence it
      could be used to study the epidemiological situation in a given area, as well as
      to assess host suitability for the parasite.

PMID- 16427205
TI  - Adjuvant docetaxel plus doxorubicin and cyclophosphamide increases survival
      compared with fluorouracil plus doxorubicin and cyclophosphamide in women with
      operable node-positive breast cancer.

PMID- 16427204
TI  - Mammalian expression of full-length bovine aggrecan and link protein: formation
      of recombinant proteoglycan aggregates and analysis of proteolytic cleavage by
      ADAMTS-4 and MMP-13.
AB  - Aggrecan, a large chondroitin sulfate (CS) and keratan sulfate (KS) proteoglycan,
      has not previously been expressed as a full-length recombinant molecule. To
      facilitate structure/function analysis, we have characterized recombinant bovine
      aggrecan (rbAgg) and link protein expressed in COS-7 cells. We demonstrate that C
      terminally truncated rbAgg was not secreted. Gel filtration chromatography of
      rbAgg and isolated glycosaminoglycan (GAG) chains, and their susceptibility to
      chondroitinase ABC digestion indicate that the GAG chains are predominantly CS,
      which likely occupy fewer serine residues than native aggrecan. To confirm
      functionality, we determined that rbAgg bound hyaluronan and recombinant link
      protein to form proteoglycan aggregates. In addition, cleavage of rbAgg by ADAMTS
      4 revealed that the p68 form of ADAMTS-4 preferentially cleaves within the CS-2
      domain, whereas the p40 form only effectively cleaves within the interglobular
      domain (IGD). MMP-13 cleaved rbAgg within the IGD, but cleaved more rapidly at a
      site within the CS domains, suggesting a role in C-terminal processing of
      aggrecan. Our results demonstrate that recombinant aggrecan can be used for in
      vitro analyses of matrix protease-dependent degradation of aggrecan in the IGD
      and CS domains, and both recombinant aggrecan and link protein can be used to
      study the assembly of proteoglycan aggregates with hyaluronan.

PMID- 16427206
TI  - Adding a single high-dose chemotherapy cycle to three cycles of standard salvage
      chemotherapy for relapsed germ-cell tumours does not improve clinical outcomes.

PMID- 16427207
TI  - In vivo protection by the xanthate tricyclodecan-9-yl-xanthogenate against
      amyloid beta-peptide (1-42)-induced oxidative stress.
AB  - Considerable evidence supports the role of oxidative stress in the pathogenesis
      of Alzheimer's disease. One hallmark of Alzheimer's disease is the accumulation
      of amyloid beta-peptide, which invokes a cascade of oxidative damage to neurons
      that can eventually result in neuronal death. Amyloid beta-peptide is the main
      component of senile plaques and generates free radicals ultimately leading to
      neuronal damage of membrane lipids, proteins and nucleic acids. Therefore,
      interest in the protective role of different antioxidant compounds has been
      growing for treatment of Alzheimer's disease and other oxidative stress-related
      disorders. Among different antioxidant drugs, much interest has been devoted to
      "thiol-delivering" compounds. Tricyclodecan-9-yl-xanthogenate is an inhibitor of
      phosphatidylcholine specific phospholipase C, and recent studies reported its
      ability to act as a glutathione-mimetic compound. In the present study, we
      investigate the in vivo ability of tricyclodecan-9-yl-xanthogenate to protect
      synaptosomes against amyloid beta-peptide-induced oxidative stress. Gerbils were
      injected i.p. with tricyclodecan-9-yl-xanthogenate or with saline solution, and
      synaptosomes were isolated from the brain. Synaptosomal preparations isolated
      from tricyclodecan-9-yl-xanthogenate injected gerbils and treated ex vivo with
      amyloid beta-peptide (1-42) showed a significant decrease of oxidative stress
      parameters: reactive oxygen species levels, protein oxidation (protein carbonyl
      and 3-nitrotyrosine levels) and lipid peroxidation (4-hydroxy-2-nonenal levels).
      Our results are consistent with the hypothesis that modulation of free radicals
      generated by amyloid beta-peptide might represent an efficient therapeutic
      strategy for treatment of Alzheimer's disease and other oxidative-stress related
      disorders. Based on the above data, we suggest that tricyclodecan-9-yl
      xanthogenate is a potent antioxidant and could be of importance for the treatment
      of Alzheimer's disease and other oxidative stress-related disorders.

PMID- 16427209
TI  - Effect of prenatal exposure to ethanol on glutamate and GABA immunoreactivity in
      macaque somatosensory and motor cortices: critical timing of exposure.
AB  - The present study explored the effects of gestational ethanol exposure on
      enduring changes in the distribution of projection neurons and local circuit
      neurons in somatosensory/motor cortex. Critical events in corticogenesis occur
      during macaque gestation: the first six weeks of gestation include the period of
      primary stem cell production and the next 18 weeks are marked by the birth,
      migration, early differentiation, and death of cortical neurons. Monkeys were
      exposed to ethanol (or saline) one day per week during the first six or during
      the entire 24 weeks of gestation. Offspring were killed as adolescents.
      Projection neurons and local circuit neurons were identified
      immunohistochemically with antibodies directed against glutamate and anti-GABA,
      respectively. In all animals, both projection neurons and local circuit neurons
      were distributed in all laminae of both somatosensory and motor cortices. Ethanol
      did not affect the size of Cresyl Violet-stained, glutamate-positive, or GABA
      immunolabeled somata, however, it did decrease neuronal density. The total
      density of Cresyl Violet-stained neurons was reduced in monkeys treated with
      ethanol (or saline) one day per week during the first six weeks of gestation and
      during the entire 24 weeks of gestation. Similar reductions were detected for
      glutamate- and GABA-positive neurons. The densities of Cresyl Violet-stained and
      of glutamate- and GABA-expressing neurons were reduced in all cortical layers.
      The only exception was layer V which was unaffected in monkeys treated with
      ethanol (or saline) one day per week during the first six weeks of gestation and
      during the entire 24 weeks of gestation. Thus, the parallel effects on both
      neuronal subpopulations suggest that ethanol targets a population of undetermined
      neuronal precursors.

PMID- 16427210
TI  - Axon initial segment ensheathed by extracellular matrix in perineuronal nets.
AB  - Perineuronal nets of extracellular matrix are associated with distinct types of
      neurons in the cerebral cortex and many subcortical regions. Large complexes of
      aggregating proteoglycans form a chemically specified microenvironment around the
      somata, proximal dendrites and the axon initial segment, including the
      presynaptic boutons attached to these domains. The subcellular distribution and
      the temporal course of postnatal formation suggest that perineuronal nets may be
      involved in the regulation of synaptic plasticity. Here we investigate structural
      and cytochemical characteristics of the extracellular matrix around axon initial
      segments virtually devoid of synaptic contacts. Wisteria floribunda agglutinin
      staining, the immunocytochemical detection of aggrecan and tenascin-R, as well as
      affinity-labeling of hyaluronan were used to analyze perineuronal nets associated
      with large motoneurons in the mouse superior colliculus. The molecular
      composition of perineuronal nets was divergent between neurons but was identical
      around the different cellular domains of the individual neurons. The axon initial
      segments largely devoid of synapses were covered by a continuous matrix sheath
      infiltrating the adjacent neuropil. The periaxonal zone penetrated by matrix
      components often increased in diameter along the initial segment from the axon
      hillock toward the myelinated part of the axon. The axonal and somatodendritic
      domains of perineuronal nets were concomitantly formed during the first three
      weeks of postnatal development. The common molecular properties and major
      structural features of subcellular perineuronal net domains were retained in
      organotypic midbrain slice cultures. The results support the hypothesis that the
      aggrecan-related extracellular matrix of perineuronal nets provides a continuous
      micromilieu for different subcellular domains performing integration and
      generation of the electrical activity of neurons.

PMID- 16427212
TI  - A phase III randomized trial of postoperative pelvic irradiation in Stage IB
      cervical carcinoma with poor prognostic features: follow-up of a gynecologic
      oncology group study.
AB  - PURPOSE: To investigate, in a phase III randomized trial, whether postoperative
      external-beam irradiation to the standard pelvic field improves the recurrence
      free interval and overall survival (OS) in women with Stage IB cervical cancers
      with negative lymph nodes and certain poor prognostic features treated by radical
      hysterectomy and pelvic lymphadenectomy. METHODS AND MATERIALS: Eligible patients
      had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the
      following features: more than one third (deep) stromal invasion, capillary
      lymphatic space involvement, and tumor diameter of 4 cm or more. The study group
      included 277 patients: 137 randomized to pelvic irradiation (RT) and 140
      randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23
      fractions to 50.4 Gy in 28 fractions. RESULTS: Of the 67 recurrences, 24 were in
      the RT arm and 43 were in the OBS arm. The RT arm showed a statistically
      significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90%
      confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically
      significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40
      to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or
      adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences
      were seen with RT in patients with adenocarcinoma or adenosquamous histologies
      relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to
      0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred:
      27 RT patients and 40 OBS patients. The improvement in overall survival (HR =
      0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical
      significance. CONCLUSIONS: Pelvic radiotherapy after radical surgery
      significantly reduces the risk of recurrence and prolongs progression-free
      survival in women with Stage IB cervical cancer. RT appears to be particularly
      beneficial for patients with adenocarcinoma or adenosquamous histologies.
      Circumstances that may have influenced the overall survival differences are
      considered.

PMID- 16427211
TI  - Early initiation of salvage hormone therapy influences survival in patients who
      failed initial radiation for locally advanced prostate cancer: A secondary
      analysis of RTOG protocol 86-10.
AB  - PURPOSE: We examined overall and disease-specific survival outcomes both from the
      time of initial treatment and from the start of salvage hormone therapy (HT), by
      the extent of disease progression at the time salvage HT was started in patients
      treated on RTOG Protocol 86-10. METHODS: [corrected] With a median follow-up of
      9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall
      survival (OVS) and disease-specific survival (DSS) were compared by the extent of
      disease progression at the time salvage HT was started. RESULTS: For those
      patients with distant metastases (DM) present at the start of salvage HT, the OVS
      and DSS were significantly reduced when compared to [corrected] those with DM
      absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8
      years, 38% vs. 65%). A statistically significant increase in DSS was observed
      among the 143 patients with DM absent when patients with prostate-specific
      antigen (PSA) less than 20 were compared with those with PSA greater than 20 at
      the time salvage HT was started. CONCLUSION: [corrected] The DSS and the OVS of
      the relapsed patient are decreased in those with more extensive disease at the
      time of salvage HT. However, because this protocol could not evaluate the effect
      of posttreatment PSA velocity on outcomes, which is likely a better predictor of
      long-term success with salvage HT, these results cannot be taken to demonstrate
      that early salvage HT in patients with long posttreatment PSA doubling times is
      necessary for longer survival.

PMID- 16427213
TI  - Impact of TBI on late effects in children treated by megatherapy for Stage IV
      neuroblastoma. A study of the French Society of Pediatric oncology.
AB  - PURPOSE: To determine the contribution of total body irradiation (TBI) to late
      sequelae in children treated with high-dose chemotherapy and autologous bone
      marrow transplantation for Stage IV neuroblastoma. PATIENTS AND METHODS: We
      compared two populations that were similar with regard to age, stage, pre
      autologous bone marrow transplantation chemotherapy (CT) regimen, period of
      treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part
      of the megatherapy procedure (1982-1993), whereas the CT group (n = 30) received
      conditioning without TBI (1985-1992). Analysis 12 years later focused on growth,
      weight and corpulence (body mass index) delay; hormonal deficiencies; liver,
      kidney, heart, ear, eye, and dental sequelae; school performance; and the
      incidence of secondary tumors. RESULTS: Impact of TBI was most marked in relation
      to growth and weight delay, although the mean delay was not severe, probably
      because of treatment with growth hormones. Other consequences of TBI were thyroid
      insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss
      and dental agenesis were more prominent in the group treated with CT alone. No
      differences were observed in school performance. CONCLUSION: The most frequent
      side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but
      more worrying is the risk of secondary tumors. Because of the young mean age of
      patients and the toxicity of TBI regimens without any survival advantage,
      regimens without TBI are preferable in the management of Stage IV neuroblastoma.

PMID- 16427214
TI  - The impact of heterogeneity correction on dosimetric parameters that predict for
      radiation pneumonitis.
AB  - PURPOSE: To determine if heterogeneity correction significantly affects commonly
      measured dosimetric parameters predicting pulmonary toxicity in patients
      receiving radiation for lung cancer. METHODS AND MATERIALS: Sixty-eight patients
      treated for lung cancer were evaluated. The conformal treatment technique mostly
      employed anteroposterior/posterior-anterior fields and off-cord obliques. The
      percent total lung volume receiving 20 Gy or higher (V20) and mean lung dose
      (MLD) were correlated with the incidence of radiation pneumonitis. Parameters
      from both heterogeneity-corrected and heterogeneity-uncorrected plans were used
      to assess this risk. RESULTS: Univariate analysis revealed a significant
      correlation between the development of radiation pneumonitis and both V20 and
      MLD. A best-fit line to a plot of V20 from the homogeneous plan against the
      corresponding V20 heterogeneous value produced a slope of 1.00 and zero offset,
      indicating no difference between the two parameters. For MLD, a similarly
      significant correlation is seen between the heterogeneous and homogeneous
      parameters, indicating a 4% difference when correcting for heterogeneity. A
      significant correlation was also observed between the MLD and V20 parameters (p <
      0.0001). CONCLUSIONS: A high degree of correlation exists between heterogeneity
      corrected and heterogeneity-uncorrected dosimetric parameters for lung and the
      risk of developing pneumonitis. Either V20 or MLD predicts the pneumonitis risk
      with similar effect.

PMID- 16427215
TI  - An ERP study of temporal discrimination in rats.
AB  - In this study, we examined event-related potentials (ERPs) in rats performing a
      timing task. The ERPs were recorded during a timing task and a control task from
      five regions (frontal cortex, striatum, hippocampus, thalamus, and cerebellum)
      that are related to time perception. In the timing task, the rats were required
      to judge the interval between two tones. This interval could be either 500 or
      2000 ms. In the control task, only the 500 ms interval between tones was
      presented and only one lever was available for responses. Any difference in ERPs
      between the two tasks was considered to reflect the processes that are related to
      temporal discrimination. The frontal cortex, striatum, and thalamus yielded
      concurrent differences in ERPs between the two tasks. The results suggest that
      these regions might play an important role in temporal discrimination.

PMID- 16427217
TI  - Improvement and validation of RAPD in combination with PFGE analysis of
      Salmonella enterica ssp. enterica serovar Senftenberg strains isolated from feed
      mills.
AB  - In 1995 and 1996 a Swedish feed mill had problems due to a persistent
      contamination of Salmonella enterica spp. enterica serovar Senftenberg that was
      difficult to eliminate. Forty-eight strains isolated from the feed mill, together
      with unrelated strains included to evaluate the discriminatory power and
      reproducibility, were analysed by pulsed-field gel electrophoresis (PFGE). The
      source of contamination in the feed mill was identified and preventative measures
      were taken, that led to a resolution of the problem. A previously developed
      randomly amplified polymorphic DNA (RAPD) protocol was used, to evaluate a rapid
      and low-cost alternative to PFGE typing. The use of the alternative thermostable
      DNA polymerase Tth was shown to increase the reproducibility of the RAPD
      analysis. The reproducibility, in terms of Pearson's and Dice's similarity
      coefficients for duplicate runs, increased from 72.0 +/- 16.9% and 72.3 +/- 12.9%
      for Taq to 91.6 +/- 7.5% and 90.9 +/- 5.3% for the fingerprints obtained for the
      RAPD method employing Tth DNA polymerase. Simpson's index of diversity was
      calculated and found to be 0.580 for RAPD and 0.896 for PFGE. All of the seven
      RAPD types could be subdivided into one or more PFGE types, whereas none of the
      22 PFGE types was divided into more than one RAPD type. RAPD provides a simple,
      rapid and powerful screening method that can be used to initially select isolates
      for further analysis by PFGE.

PMID- 16427216
TI  - Comparison of protection levels against pseudorabies virus infection of
      transgenic mice expressing a soluble form of porcine nectin-1/HveC and vaccinated
      mice.
AB  - We recently generated transgenic mice expressing a soluble form of porcine nectin
      1 (PHveCIg) showing remarkable resistance to pseudorabies virus (PRV) infection.
      Nectin-1, also known as herpesvirus entry mediator C (HveC), is an
      alphaherpesvirus receptor that binds to virion glycoprotein D (gD). In order to
      evaluate the level of resistance to PRV infection induced by the expression of
      PHveCIg in the transgenic mice, the protective effects of vaccinated and
      transgenic mice were directly compared. Mice were immunized with a live vaccine,
      through intraperitoneal injection of PRV strain Begonia (an attenuated vaccine
      strain deleted for gE and thymidine kinase genes) at 4 weeks before challenge.
      The vaccinated and transgenic mice were challenged with 10LD(50), 20LD(50) or
      50LD(50) of PRV strainYS-81 via intranasal route. In the vaccinated mice, no
      protection was observed in the challenges with 20LD(50) and 50LD(50). Only two
      out of six vaccinated mice survived in the challenge with 10LD(50). In contrast,
      four transgenic mouse lines showed significant resistance to PRV infection,
      although the survival rates varied in the challenge with each viral dose. These
      results demonstrate clearly the high potential of transgenic strategy in control
      of pseudorabies.

PMID- 16427218
TI  - Virulence genotype of Pasteurella multocida strains isolated from different hosts
      with various disease status.
AB  - To learn more about the molecular biology of Pasteurella multocida 289 strains
      isolated from various clinically healthy and diseased hosts were examined for
      capsule biosynthesis genes (capA, B, D, E, and F) and 14 virulence associated
      genes by PCR and DNA-DNA-hybridization. As expected, capsule type A strains were
      highly adapted to bovines (92.3%) and poultry (85.7%) while we mainly found capA
      (34.9%)- and capD (58.1%)-positive strains in swine. A noticeable amount of capD
      positive strains also originated from small ruminants (34.9%) and capF was
      detected in wild type strains from diseased cattle (2.2%) and cats (7.4%). None
      of the isolates harboured capE, while capB was exclusively found in all strains
      from buffaloes. Nearly all isolates showed a combination of genes encoding outer
      membrane proteins, colonization factors, iron aquisition factors and superoxid
      dismutases without any clue for host specificity. In contrast, the transferrin
      binding protein encoding gene tbpA (31.5%) was limited to ruminant strains and
      only 37.0% of all P. multocida strains harboured pfhA, coding for a filamentous
      hemagglutinin, supposed to be a putative adhesion- und serum resistance factor.
      PfhA revealed a strong positive association to the outcome of disease in bovine
      hosts and in combination with toxA to that in swine. The dermonecrotoxin encoding
      toxA, present in 12.5% of all strains, was detected in isolates from swine, small
      ruminants, cattle, and poultry. A significant association to the disease status,
      however, was only existent in swine, although with 66.7% we found a notably high
      prevalence of the toxin gene among strains from small ruminants. The genes toxA,
      tbpA and pfhA as well as capsule biosynthesis genes are supposed to be important
      epidemiological marker genes for characterizing P. multocida field strains.

PMID- 16427219
TI  - Fetopathy associated with exposure to angiotensin converting enzyme inhibitors
      and angiotensin receptor antagonists.
AB  - The renin-angiotensin system plays an important role in the regulation of blood
      pressure. The use of angiotensin converting enzyme inhibitors or angiotensin
      receptor blockers both control hypertension by interruption of the production or
      action of angiotensin II, the major end-product of the renin-angiotensin system.
      The use of angiotensin converting enzyme inhibitors in pregnant women revealed
      serious and deleterious effects on fetal development including renal failure,
      renal dysplasia, hypotension, oligohydramnios, pulmonary hypoplasia, and
      hypocalvaria. The fetal effects of angiotensin converting enzyme inhibitors seem
      to be greatest during the 2nd and 3rd trimesters of pregnancy. The fetal effect
      of angiotensin converting enzyme inhibitors during the 1st trimester is
      controversial. These effects may represent the effect of hypoperfusion in the
      fetus and not a teratogenic effect. The effect of angiotensin receptor blockers
      is similar to converting enzyme inhibitors. Angiotensin converting enzyme
      inhibitors and angiotensin receptor blockers should be avoided in all pregnant
      women. Alternative antihypertensive medications should be considered for use in
      women of childbearing years.

PMID- 16427220
TI  - Management of neonatal hydronephrosis.
AB  - Management of neonatal hydronephrosis is a clinical challenge. The natural
      history of hydronephrosis has shown that most resolve spontaneously; however,
      there are a significant number that do not. Although hydronephrosis does not
      always mean obstruction, it becomes the clinician's role to determine when
      obstruction will eventually lead to renal damage. Work-up of hydronephrosis
      diagnosed prenatally starts with a postnatal ultrasound. Using the Society of
      Fetal Urology (SFU) grading of hydronephrosis based on ultrasonography, a
      management and treatment algorithm can be constructed. Other studies include a
      voiding cystourethrogram to evaluate for vesicoureteral reflux or in severe cases
      of bilateral hydronephrosis to evaluate for posterior urethral valves. Diuretic
      renography is useful in many cases to evaluate the degree of obstruction and
      determine differential renal function. The goal is to select the patients who
      would benefit from early surgical intervention. To achieve that goal, aggressive
      observation is often required.

PMID- 16427221
TI  - Computer assisted image analyses of corpora lutea in relation to peripheral
      concentrations of progesterone: a comparison between breeds of sheep with
      different ovulation rates.
AB  - Transrectal ovarian ultrasonography is a non-invasive technique that permits the
      real-time serial visualization of ovarian structures. Previous studies have
      reported correlations between serum progesterone concentrations and physical
      characteristics of the corpus luteum (CL) in different species. The aim of the
      present study was to investigate whether or not there were correlations between
      ultrasound image attributes of the CL and changing progesterone concentrations
      over time, in prolific and non-prolific ewes. Ultrasonographic images of CL were
      taken, once daily, from 12 Western White Face ewes and 7 Finn ewes for the
      duration of one luteal phase. Blood samples were collected daily prior to each
      scanning session and assayed to determine mean serum concentrations of
      progesterone. Analysis of ultrasound images was performed using a series of
      custom-developed computer algorithms optimized for ultrasonography on a computer
      graphics workstation. Both total luteal area and mean pixel values were
      correlated with the pattern of serum concentrations of progesterone from days 3
      to 15 after ovulation in Western White Face ewes and from days 3 to 14 in Finn
      ewes. There was no significant correlation between progesterone concentrations
      and spot pixel heterogeneity for either Western White Face ewes or Finn ewes. We
      concluded that pixel heterogeneity is a poor indicator of progesterone secretory
      ability of the CL when compared to mean pixel values. However, luteal area and
      mean spot pixel values are better but not strong indicators of the functional
      status of the CL in cyclic ewes.

PMID- 16427222
TI  - Influence of deposition and spray pattern of nasal powders on insulin
      bioavailability.
AB  - The influence of the deposition pattern and spray characteristics of nasal powder
      formulations on the insulin bioavailability was investigated in rabbits. The
      formulations were prepared by freeze drying a dispersion containing a physical
      mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a
      spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition
      in the nasal cavity of rabbits and in a silicone human nose model after actuation
      of three nasal delivery devices (Monopowder, Pfeiffer and experimental system)
      was compared and related to the insulin bioavailability. Posterior deposition of
      the powder formulation in the nasal cavity lowered the insulin bioavailability.
      To study the spray pattern, the shape and cross-section of the emitted powder
      cloud were analysed. It was concluded that the powder bulk density of the
      formulation influenced the spray pattern. Consequently, powders of different bulk
      density were prepared by changing the solid fraction of the freeze dried
      dispersion and by changing the freezing rate during freeze drying. After nasal
      delivery of these powder formulations no influence of the powder bulk density and
      of the spray pattern on the insulin bioavailability was observed.

PMID- 16427223
TI  - Release behaviour and biocompatibility of drug-loaded pH sensitive particles.
AB  - The purpose of this work was to investigate the physical properties of drug
      loaded poly(methacrylic acid-g-ethylene glycol) {P(MAA-g-EG)} particles, their
      biocompatibility with the gastrointestinal tract of rats and also the effects of
      these particles on the tight junctions of the rat intestinal epithelium. Model
      drugs such as diltiazem HCl, diclofenac Na, ciprofloxacin HCl and isoniazid were
      used in this study. P(MAA-g-EG) particles were prepared by free radical solution
      polymerization of methacrylic acid (MAA) and poly(ethylene glycol) (PEG). The
      loading efficiency of the model drugs in the particles and in vitro release
      profiles were investigated in pH 7.4 phosphate buffer and in gradually pH
      changing buffers (pH 1.2, 5.8, 6.8 and 7.4). The stability of free particles and
      drug-loaded particles was established by Fourier transform infrared spectroscopy
      (FT-IR) and differential scanning calorimetry (DSC). In conclusion, P(MAA-g-EG)
      particles controlled the release rate of small molecular weight model drugs
      according to the pH of the medium. Stability of those particles loaded with drugs
      did not change in accelerated stability conditions. Histopathological results
      indicated that loading drugs to the particles prevented cell and tissue damage
      after 20 h. Free particles showed no change of tight junctions after 2 and 10 h.
      The results of TEM showed that increasing the amount of P(MAA-g-EG) particles
      from 100 to 385 mg clearly opened the tight junction, but with serious epithelial
      cell disruption.

PMID- 16427224
TI  - Calorimetric investigation of protein/amino acid interactions in the solid state.
AB  - Possible protein/amino acid interactions and the physical states of amino acids
      after freeze-drying have been studied using isoperibol calorimetry and
      differential scanning calorimetry (DSC). Good linear correlations (R(2) = 0.99)
      between the enthalpies of solution and the percentage of antibody in all physical
      mixtures, as well as unchanging melting temperatures of amino acids for physical
      mixtures demonstrated that there is no interaction between the antibodies and
      amino acids studied upon physical mixing. On the other hand, positive deviations
      for antibody/histidine and antibody/arginine freeze-dried samples obtained from
      the isoperibol calorimetry results demonstrated that molecular level
      interactions, such as ion-dipole or electrostatic interactions or hydrogen
      bonding, occur between antibodies and histidine or arginine. The values of
      DeltaH(interaction) for antibody/histidine (1:1, w/w) and antibody/arginine (1:1,
      w/w) lyophilized samples were approximately 8 kJ/mol. These interactions were
      also confirmed by decreased and/or the disappearance of melting temperatures of
      the amino acids with DSC measurements. A negative deviation from linearity was
      detected for antibody/aspartic acid lyophilized samples which indicated partial
      amorphization of aspartic acid. No deviation from linearity as well as similar
      melting temperatures of antibody/glycine lyophilized samples indicated the
      absence of interactions between the antibodies and glycine upon freeze-drying.

PMID- 16427225
TI  - Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N
      stearyllactobionamide-modified liposomes and their enhanced cellular biological
      effects.
AB  - Short (14-20-mer range) synthetic oligodeoxynucleotides (ODNs) allow specific
      modulation of cellular gene expression at various stages, thus providing a
      versatile tool for fundamental studies and a rational approach to anticancer
      chemotherapy. However, several problems, such as metabolic stability, efficient
      cell internalization of ODNs and their efficient entrapment into liposomes
      continue to markedly limit this approach. To improve the target specificity and
      biological activity of ODN, three different length of poly(L-lysine) (PLL) were
      conjugated to ODN and these conjugates were encapsulated in N
      stearyllactobionamide (N-SLBA)-modified liposomes, N-SLBA is a ligand for the
      asialoglycoprotein receptor. Then, we investigated their effects on cell cycle
      and survivin protein levels of HepG2 cells. The results showed that the
      encapsulation efficiency was improved because the polycationic charges of PLL
      neutralized the polyanionic charges of ODN. Among them, PLL (M(W) 2000 and
      10,000)-conjugated ODN encapsulated in N-SLBA liposomes induced apoptosis of
      HepG2 cells and highly inhibited survivin gene expression.

PMID- 16427226
TI  - Characterization of the molecular distribution of drugs in glassy solid
      dispersions at the nano-meter scale, using differential scanning calorimetry and
      gravimetric water vapour sorption techniques.
AB  - The molecular distribution in fully amorphous solid dispersions consisting of
      poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass
      transition temperature (T(g)), as determined by temperature modulated
      differential scanning calorimetry (TMDSC), was observed in PVP-diazepam solid
      dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g)
      of these solid dispersions gradually changed with composition and decreased from
      177 degrees C for pure PVP to 46 degrees C for diazepam. These observations
      indicate that diazepam was dispersed in PVP on a molecular level. However, in PVP
      diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed
      for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the
      presence of amorphous diazepam clusters, the other T(g) was attributed to a PVP
      rich phase in which diazepam was dispersed on a molecular level. With both the
      value of the latter T(g) and the DeltaC(p) of the diazepam glass transition the
      concentrations of molecular dispersed diazepam could be calculated (27-35 wt.%).
      Both methods gave similar results. Water vapour sorption (DVS) experiments
      revealed that the PVP-matrix was hydrophobised by the incorporated diazepam.
      TMDSC and DVS results were used to estimate the size of diazepam clusters in
      freeze dried PVP-diazepam solid dispersions, which appeared to be in the nano
      meter range. The inulin-diazepam solid dispersions prepared by spray freeze
      drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous
      distribution on a molecular level. However, this T(g) was independent of the drug
      load, which is unexpected because diazepam has a lower T(g) than inulin (46 and
      155 degrees C, respectively). For higher drug loads, a T(g) of diazepam as well
      as a T(g) of the inulin-rich phase was observed, indicating the formation of
      amorphous diazepam clusters. From the DeltaC(p) of the diazepam glass transition
      the amount of molecularly dispersed diazepam was calculated (12-27 wt.%). In
      contrast to the PVP-diazepam solid dispersions, DVS-experiments revealed that
      inulin was not hydrophobised by diazepam. Consequently, the size of diazepam
      clusters could not be estimated. It was concluded that TMDSC enables
      characterization and quantification of the molecular distribution in amorphous
      solid dispersions. When the hygroscopicity of the carrier is reduced by the drug,
      DVS in combination with TMDSC can be used to estimate the size of amorphous drug
      clusters.

PMID- 16427227
TI  - Panax notoginseng attenuates LPS-induced pro-inflammatory mediators in RAW264.7
      cells.
AB  - Herbals or dietary supplements are not regulated as drugs by the United States
      Food and Drug Administration (USFDA) although many may have associated
      therapeutic effects and toxicities. Therefore, the immunomodulatory effects of
      the herbal extract Panax notoginseng on cultured macrophages (RAW264.7 cells)
      were investigated to address potential therapeutic or toxic effects. Cells were
      stimulated with LPS (1 microg/ml) and treated with notoginseng at 5, 25 and 50
      microg/ml. Notoginseng inhibited the LPS-induced production of TNF-alpha and IL-6
      by the cultured macrophages in a concentration-dependent manner. The expression
      of COX-2 and IL-1 beta mRNA was also attenuated by notoginseng. TNF-alpha
      production was inhibited in samples treated with notoginseng 24h before, or at
      the same time as LPS stimulation, but not in samples treated 8h after LPS
      stimulation. Notoginseng reduced expression of the accessory molecules CD40 and
      CD86 on the RAW264.7 cells while CD14 and TLR4 expression remained unaffected.
      Furthermore, Rb1 and Rg1 ginsenosides also inhibited macrophage production of TNF
      alpha, but to a lesser extent than did the whole notoginseng extract.
      Collectively, these results indicate that notoginseng inhibits LPS-induced
      activation of RAW264.7 macrophages and demonstrates that notoginseng possesses
      anti-inflammatory and immunosuppressive properties in vitro.

PMID- 16427228
TI  - Evaluation of the antioxidant properties and bioavailability of free and bound
      phenolic acids from Trichilia emetica Vahl.
AB  - Trichilia emetica Vahl. is commonly used in folk medicine of Mali for the
      treatment of various diseases. In this study, the content and the antioxidant
      activity of phenolic acids from Trichilia emetica root were evaluated. Free
      phenolic acids were extracted with a mixture of methanol and 10% acetic acid.
      Bound phenolic acids were released using first alkaline and then acid hydrolysis.
      All fractions were quantified separately by HPLC. After alkaline hydrolysis, a
      remarkable increase in caffeic acid, ferulic acid, p-coumaric acid, syringic
      acid, vanillic acid, protocathecuic acid and gallic acid content was observed,
      showing that most of phenolic acids in the drug are present as bound forms.
      Moreover, the extracts submitted to alkaline hydrolysis showed high antioxidant
      properties in two in vitro assays: autooxidation of methyl linoleate (MeLo) and
      ascorbate/Fe(2+)-mediated lipid peroxidation in rat microsomes. An in vivo study
      was also performed to investigate the intestinal absorption of phenolic acids
      after oral administration of Trichilia emetica extracts. Results showed high
      levels of phenolic acids, free or conjugated to glucuronide, in the plasma of
      rats treated with the hydrolyzed extract. Due to the absence of chlorogenic acid
      in plasma samples, the presence of caffeic acid seems to be derived from
      hydrolysis of chlorogenic acid in the gastrointestinal tract.

PMID- 16427229
TI  - Comparison of pulmonary autopsy findings of the rats drowned at surface and 50 ft
      depth.
AB  - INTRODUCTION: When a body is recovered from the water after a fatal SCUBA diving
      accident, it is useful to know if the diver was under pressure or not when he/she
      took his/her last breath, in order to determine the cause and manner of the
      death. If the victim was under pressure, the air remained in the lungs of the
      diver will be equal to the environmental pressure. If the body comes to the
      surface, the air in the lung will expand according to the Boyle's Gas Law and
      give mechanical damage to the surrounding tissues, due to decreases in
      environmental pressure. We designed an experimental study to see the difference
      in pulmonary autopsy findings of the rats that drowned under normobaric and
      hyperbaric conditions. METHOD: Forty five male, 250-300 g, Sprague Downey adult
      rats were divided into three groups. Two groups of rats were drowned under
      normobaric conditions (Groups DS Group DSS) and the third group at 50 ft pressure
      (Group DD). The pulmonary autopsy findings of the groups were compared. In the
      light microscopy, the number of the microscopic fields (x10) containing at least
      one emphysematous area with longitudinal dimension greater than 300 micro m were
      compared among the groups. RESULTS: The gross examination revealed a prominent
      swelling of the lungs in all rats in the Group DD, in comparison to that of the
      Groups DS and DSS. The number of the microscopic fields, which included at least
      one emphysematous area with longitudinal dimension greater than 300 micro m out
      of 150 fields from each of the groups DS, DSS and DD, were 88, 101 and 115
      respectively. The difference between the group DS and DD was found to be
      statistically significant. CONCLUSION: We conclude that in investigating the
      fatal diving accidents, pulmonary autopsy findings give valuable information
      whether the death occurred at the surface or at the depth.

PMID- 16427230
TI  - Persons found 'not criminally responsible on account of mental disorder': a
      comparison of British Columbia, Canada and Hunan, China.
AB  - Current research literature contains very few international, cross-cultural
      comparison studies of persons adjudicated 'Not Criminally Responsible on Account
      of Mental Disorder' (NCRMD). This study explores and compares the demographic
      differences between persons found NCRMD in British Columbia, Canada and Hunan,
      China. Eight variables such as sex, age, education level, marital status,
      conviction history, psychiatric history, and index offence are compared between
      the Canadian and Chinese cohorts. The Canadian and Chinese cohorts were similar
      in sex and psychiatric history. The divorce rate, educational level, and
      conviction histories were significantly higher, and the age was significantly
      older in the Canadian cohort. The Chinese cohort had higher levels of murder and
      attempted murder index offences. Differences between the two cohorts can be
      explained in terms of legislative and cultural differences.

PMID- 16427232
TI  - Collagen changes in the cochlea of aged Fischer 344 rats.
AB  - Hearing function in the Fischer 344 (F344) albino inbred strain of rats
      deteriorates with aging faster than in other strains, in spite of the small hair
      cell loss in old F344 animals [Popelar, J., Groh, D., Pelanova, J., Canlon, B.,
      Syka, J., 2005. Age-related changes in cochlear and brainstem auditory function.
      Neurobiol. Aging, in press.]. This study was aimed at elucidating the structural
      changes in the inner ear of this rat strain during aging. Cochlear histopathology
      was examined in 20-24-month-old F344 rats and compared with that of young F344
      rats (4 months) and of old rats of the Long-Evans (LE) strain. Hematoxylin/eosin
      staining in aged F344 rats showed degenerative changes in the organ of Corti,
      consisting of a damaged layer of marginal cells, reduced vascularization of the
      stria vascularis and a distorted tectorial membrane detached from the organ of
      Corti. Age-related changes in collagen distribution were observed with Masson's
      trichrome staining in the spiral ligament of old F344 rats. The results of
      immunohistochemical staining for type II collagen revealed a marked decrease in
      collagen fibers in the area connecting the spiral ligament and stria vascularis
      and a decrease in area IV fibrocytes in old F344 but not in LE rats. These
      findings may contribute to an explanation of the substantial hearing loss found
      in old F344 rats.

PMID- 16427231
TI  - Targeting mechanisms of Pseudomonas aeruginosa pathogenesis.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen responsible for ventilator
      acquired pneumonia, acute lower respiratory tract infections in immunocompromised
      patients and chronic respiratory infections in cystic fibrosis patients. High
      incidence, infection severity and increasing resistance characterize P.
      aeruginosa infections, highlighting the need for new therapeutic options. One
      such option is to target the many pathogenic mechanisms conferred to P.
      aeruginosa by its large genome encoding many different virulence factors. This
      article reviews the pathogenic mechanisms and potential therapies targeting these
      mechanisms in P. aeruginosa respiratory infections.

PMID- 16427233
TI  - Effect of age on insulin-induced endothelin release and vasoreactivity in
      hypertriglyceridemic and hypertensive rats.
AB  - In the present paper, the age-related changes in the vasoconstrictive endothelin
      mediated response to insulin in aortas of normal and hypertensive,
      hypertriglyceridemic, hyperinsulinemic (HTG) rats were studied. To develop HTG
      rats, weanling male Wistar animals were given 30% sucrose in their drinking water
      for 4, 6, 12 and 18 months. Blood pressure was increased in HTG rats for up to 12
      months showing a maximum at 6 months (138.9+/-0.8 mmHg). In vitro contractions
      were elicited with 40 mM KCl in the presence and absence 50 microU/ml insulin and
      of endothelin-receptor antagonists BQ123 and BQ788. Tension development to KCl
      was not modified during aging in control rats but was increased at 4 and 6 months
      in HTG rats. Increased endothelin release induced by insulin remained constant in
      normal rats, while in HTG rats it was higher than in controls at all ages. ET(A)
      blocker participation alone increased during aging in control rats while both
      receptor blockers participated in HTG rats. Our results suggest that the
      vasoconstrictive capacity to KCl plus insulin decreases during aging and that
      this decrease is greater in HTG rats. The participation of endothelin receptors
      in the aging process differs in control and HTG rats.

PMID- 16427234
TI  - Telomeres, immune aging and autoimmunity.
AB  - Telomere length is important in constraining the replicative potential of cells;
      cellular systems that are dependent on cell replenishment for renewal or on cell
      proliferation for functionality are highly sensitive to telomeric erosion. Cell
      replication invariably leads to telomere loss, which, in some cellular systems,
      is partially compensated for by telomerase activity. In addition to this typical
      telomere loss, several mechanisms of sporadic telomere loss exist. Heterogeneity
      in age-dependent telomere loss can be a consequence of increased cellular
      turnover during a lifetime, accelerated telomeric DNA damage, or defects in
      telomere repair. The immune system is a prime example of a highly dynamic
      cellular system, for which telomere maintenance is pivotal. Immune competence is
      strictly dependent on rapid expansions of clonal T- and B-cell populations, and
      telomere loss may contribute to defective immune responses in the elderly.
      Equally interestingly, accelerated T-cell aging combined with telomeric
      shortening may predispose for autoimmune responses and thereby explain the
      increased susceptibility for chronic inflammatory diseases in the elderly.

PMID- 16427235
TI  - Republication of SEMPET trial data?
AB  - Becherer and colleagues' report in the European Journal of Radiology of their
      interesting data on the use of FDG PET in the evaluation of residual masses in
      seminoma patients is extremely similar to the data that the same authors
      published in 2004 in the Journal of Clinical Oncology. It would be very helpful
      to know whether these are the same patients being presented again or a new
      multicenter study of the same size asking the same question. Oddly, the authors
      do not acknowledge their prior report even though it was published the same month
      that the report to the European Journal of Radiology was submitted for review. It
      would be helpful if the authors explained what the 2005 report adds to the 2004
      report for those of us trying to assess the role of FDG PET in this patient
      population. At this point in time, it appears that there are two studies that
      have been completed, including a negative trial from the United States and a
      positive trial (now published three times) from Europe.

PMID- 16427236
TI  - Pictorial review: electron beam computed tomography and multislice spiral
      computed tomography for cardiac imaging.
AB  - Electron beam computed tomography (EBCT) revolutionized cardiac imaging by
      combining a constant high temporal resolution with prospective ECG triggering.
      For years, EBCT was the primary technique for some non-invasive diagnostic
      cardiac procedures such as calcium scoring and non-invasive angiography of the
      coronary arteries. Multislice spiral computed tomography (MSCT) on the other hand
      significantly advanced cardiac imaging through high volume coverage, improved
      spatial resolution and retrospective ECG gating. This pictorial review will
      illustrate the basic differences between both modalities with special emphasis to
      their image quality. Several experimental and clinical examples demonstrate the
      strengths and limitations of both imaging modalities in an intraindividual
      comparison for a broad range of diagnostic applications such as coronary artery
      calcium scoring, coronary angiography including stent visualization as well as
      functional assessment of the cardiac ventricles and valves. In general, our
      examples indicate that EBCT suffers from a number of shortcomings such as limited
      spatial resolution and a low contrast-to-noise ratio. Thus, EBCT should now only
      be used in selected cases where a constant high temporal resolution is a crucial
      issue, such as dynamic (cine) imaging. Due to isotropic submillimeter spatial
      resolution and retrospective data selection MSCT seems to be the non-invasive
      method of choice for cardiac imaging in general, and for assessment of the
      coronary arteries in particular. However, technical developments are still needed
      to further improve the temporal resolution in MSCT and to reduce the substantial
      radiation exposure.

PMID- 16427237
TI  - Application of LC-ESI-MS-MS for detection of synthetic adulterants in herbal
      remedies.
AB  - Adulteration of allegedly "natural herbal medicines" with undeclared synthetic
      drugs is a common and dangerous phenomenon of alternative medicine. The purpose
      of the study was to develop a procedure for detection of most common synthetic
      adulterants in herbal remedies, using high-pressure liquid chromatography
      electrospray tandem mass spectrometry (LC-ESI-MS-MS). Eighty drugs belonging to
      various pharmacological classes were included in the study. For most drugs two
      transitions were monitored, using protonated or deprotonated molecules as
      precursor ions. The drugs were isolated from herbal remedies using simple
      methanol extraction. Chromatographic separation was done in gradient of
      acetonitrile-10 mM ammonium formate buffer (pH 3.0). Drugs tested were grouped in
      suites, comprising analgesic drugs, antibiotics, antidiabetic drugs,
      antiepileptic drugs, aphrodisiacs, hormones and anabolic drugs, psychotropic
      drugs, and weight reducing compounds. These suites were used according to the
      declared benefits of examined preparations. Limits of detection ranged from 5 pg
      to 1 ng per injected sample. Drug-free herbal remedy spiked with eight various
      pharmaceuticals occurring in adulterated herbal preparations was used for
      internal proficiency testing. The recoveries of spiked drugs ranged from 63 to
      100%. The procedure was applied in everyday casework. Several undeclared drugs
      were identified in "herbal" remedies, like e.g. sildenafil, tadalafil,
      testosterone, or glibenclamide. Pharmacological properties of detected drugs
      always corresponded with the claims of the "natural" remedies. The method
      presents a valuable extension of standard GC-MS screening used for this purpose.

PMID- 16427238
TI  - Analysis of some steroids by thin-layer chromatography using optimum mobile
      phases.
AB  - The aim of this paper was the analysis of five androstane isomers by thin-layer
      chromatography (TLC). The choice of proper mobile phase and the optimization of
      the mobile phase composition are very important because the chromatographic
      separation is difficult to achieve. In the first step, the proper mobile phase
      system was chosen from seven elution systems presented in the literature using
      numerical taxonomy method. The proper solvent system was found to be the mixture
      of chloroform, acetone, and petroleum ether. In the second step the composition
      of mobile phase was optimized by "simplex" method and "prisma" method. The
      optimum TLC system can be applied for the separation of androstane isomers from
      real samples such as drug formulation, biological and natural sources.

PMID- 16427239
TI  - HPLC quantitation of the four stereoisomers of benzoxathiepin derivatives with
      cellulose phenyl type chiral stationary phase and circular dichroism detection.
AB  - The chiral separation of a new antianginal agent has been investigated on a
      chiral cellulose column with UV and circular dichroism (CD) detection. This
      benzoxathiepin derivative under development has two stereogenic centers whose
      (R,S) stereoisomer shows an interesting antianginal activity. After optimisation
      of the mobile phase composition, a baseline-resolved separation of the four
      stereoisomers was achieved on a Chiralcel OJ-H chiral column by using methanol
      ethanol-diethylamine (25:75:0.1, v/v/v) as mobile phase. The CD detection system
      allowed quantitation and a linear response was observed within a 10-200 microg mL
      1 concentration range (r2=0.9966) and limit of quantification down to 2 microg mL
      1 was achieved.

PMID- 16427240
TI  - Comparison of Gram and Kopeloff stains in the diagnosis of bacterial vaginosis in
      pregnancy.
AB  - Bacterial vaginosis (BV) is commonly diagnosed by using the Nugent score, a
      semiquantitative scoring system to evaluate bacterial morphotypes on Gram stain
      of vaginal secretions. Some authors have suggested using the Kopeloff
      modification of the Gram stain. Asymptomatic BV in pregnancy has been associated
      with adverse outcomes. We performed both stains on simultaneously collected
      vaginal smears from 2652 women at 24-26 weeks of gestation. Gram staining gave
      significantly higher (more abnormal) Nugent scores than Kopeloff staining.
      Compared to the Kopeloff stain, the number of specimens graded as indeterminate
      or consistent with BV by Gram stain increased by 29% (469 versus 364, P<.001).
      Interrater reliability of the Nugent score (n=413) for Kopeloff staining was
      significantly better than Gram staining (agreement=74% versus 63%, intraclass
      correlation coefficient=0.87 versus 0.79, P<.05, 95% confidence intervals 0.85
      0.89 and 0.75-0.82, respectively).

PMID- 16427242
TI  - Comparison of the effect of delayed entry into 2 different blood culture systems
      (BACTEC 9240 and BacT/ALERT 3D) on culture positivity.
AB  - The effect of delayed entry (2-48 h) into BacTAlert 3D and BACTEC 9240 and the
      effect of 2 storage temperatures (22 degrees C vs 35 degrees C) on bacterial
      growth was evaluated. The delay in transportation of blood culture bottles stored
      at room temperature had no effect on the recovery rate for the first 12 h.
      Culture positivity was between 74.4% and 100% for different microorganisms at
      less than 24 h preincubation time. The positivity rate decreased significantly
      for Acinetobacter baumannii, Bacteroides fragilis, Escherichia coli, Enterococcus
      faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus
      pneumoniae for more than 24 h of delay. Culture positivity was higher at 22
      degrees C for all microorganisms especially for Enterococcus faecalis and P.
      aeruginosa. Effects of instrument, preincubation time, and temperature showed
      that the risk of culture negativity increased 1.5 times for BACTEC compared with
      BacTAlert 3D and increased 2.5 times for 35 degrees C compared with 22 degrees C.
      The negativity increased 5.5 times and 8.5 times at 24 and 48 h of delay
      respectively, compared with no delay.

PMID- 16427241
TI  - The first detection of CTX-M-14 extended-spectrum beta-lactamase among diverse
      beta-lactamase-producing Proteus mirabilis clinical isolates.
AB  - CTX-M-14- and -2-like extended-spectrum beta-lactamases were detected in 5 and 1
      Proteus mirabilis isolates, respectively, among 92 non-duplicate strains tested
      from December 2002 to September 2003. This is the first report of the CTX-M-14
      enzyme in P. mirabilis to the best of our knowledge and suggests that the CTX-M
      type enzyme is gradually spreading to this species. bla(TEM), bla(SHV-1), and/or
      bla(OXA-10) alleles were also detected in 35 ampicillin-resistant isolates
      tested.

PMID- 16427243
TI  - Clinical isolates of Streptococcus iniae from Asia are more mucoid and beta
      hemolytic than those from North America.
AB  - Streptococcus iniae, a widely distributed fish pathogen, is known to cause rare
      cases of human infection. We describe 2 cases of invasive S. iniae infection, one
      with septic arthritis complicating chronic gout and the other with bacteremic
      cellulitis. Both patients were Chinese and have been regularly handling fresh
      fish for cooking. Both isolates were unidentified or misidentified by 3
      commercially available identification system and were only identified by 16S rRNA
      gene sequencing. When compared with a clinical isolate of S. iniae from Canada,
      their colonies were larger, more beta-hemolytic, and microcoid. Although
      bacteremic cellulitis has been described as the most common infection associated
      with S. iniae, the bacterium has not been reported to cause exacerbations of
      gouty arthritis previously. Clinical laboratories should be aware of the
      possibility of different colony morphology of S. iniae from Asia. More accurate
      identification of nongroupable beta-hemolytic streptococci, especially from
      patients with epidemiologic linkage to fresh fish, may uncover more cases of S.
      iniae infection. The Asian population and handlers of fresh fish should be
      informed of the risk of acquiring S. iniae infection.

PMID- 16427244
TI  - British women's attitudes towards oocyte donation: ethnic differences and
      altruism.
AB  - OBJECTIVE: This study assessed the importance of altruism and willingness to
      donate oocytes in British Asian and Caucasian samples. The Theory of Planned
      Behaviour (TPB) was used to test the importance of attitudes towards oocyte
      donation, normative and control beliefs to attitudes to donate oocytes. METHOD:
      One hundred and one participants (55% Asian, 45% Caucasian) completed
      questionnaires measuring altruism and attitudes to Oocyte donation. There were no
      socio-demographic differences between ethnic groups. RESULTS: Few women were
      willing to donate oocytes, Asian women were least likely to donate oocytes, and
      altruism was not related to willingness to donate. Forty-one participants
      considered themselves 'possible' oocyte donors and 54 as definite 'non' donors.
      Possible donors reported significantly more positive attitudes towards egg
      donation; asking women to donate under various circumstances; to the consequences
      of donating their eggs; positively experiencing egg donation and to factors that
      would induce women to donate. Subjective norms and behavioural control also
      influenced intention to donate. CONCLUSION: A number of components of the TPB
      were able to predict possible oocyte donation, and non-oocyte donation. PRACTICE
      IMPLICATIONS: This study provides some empirical support for specific factors
      influencing cultural differences in gamete donation in the UK. A future
      culturally appropriate targeted approach to donation education could redress the
      present imbalance in supply and demand of gametes in infertility treatment.

PMID- 16427245
TI  - Results of a randomized study of telephone versus in-person breast cancer risk
      counseling.
AB  - OBJECTIVE: Women of all risk levels have reported high interest in obtaining
      genetic testing for breast cancer risk. Breast cancer risk counseling may help
      women to learn about their risk and appropriate options of testing. This study
      measured the effects of an intervention in-person and by telephone, compared to a
      control group. METHODS: Participants were 340 women, recruited through a network
      of primary care physicians. They received a baseline questionnaire in the mail,
      were randomized to one of the three study arms, and completed a follow-up survey
      3 months later. RESULTS: Both types of counseling were very well received. The
      counseling decreased women's cancer worry, risk perceptions, and intentions to
      pursue genetic testing. There were similar effects for both in-person and
      telephone counseling. CONCLUSION: Genetic counseling can be used to inform women
      at all risk levels about their breast cancer risk. PRACTICE IMPLICATIONS: Breast
      cancer risk counseling can be done in-person and by telephone--thereby reaching
      women in remote areas.

PMID- 16427246
TI  - Whole body MR imaging: applications in oncology.
AB  - This article reviews technique and clinical applications of whole body MR imaging
      as a diagnostic tool in cancer staging. In particular the article reviews its
      role as an alternative to scintigraphy (bone scan and PET) in staging skeletal
      spread of disease, its role in assessing total tumour burden, its role in
      multiple myeloma and finally its evolving non oncologic role predominantly
      assessing total body composition.

PMID- 16427247
TI  - Fate of Chlamydophila pneumoniae in human monocyte-derived dendritic cells: long
      lasting infection.
AB  - Earlier studies from this group demonstrated that Chlamydophila pneumoniae co
      localized with dendritic cells (DC) in temporal artery biopsies from patients
      with giant cell arteritis (GCA). To investigate the interaction of DC with C.
      pneumoniae we employed an in vitro cell culture system of human monocyte derived
      DC. These DC were infected with C. pneumoniae and observed at regular time
      intervals up to 25 days post infection. Chlamydiae were visualized inside DC by
      both confocal and electron microscopy. Statistical analysis showed an increase in
      the number of chlamydial antigen during that period (p < 0.00005, chi2-test).
      Titration of DC lysates on HEp-2 cells showed that infectious progeny was
      recovered at various intervals but showed no exponential growth. Additionally, RT
      PCR analyses of infected DC identified transcripts from dnaA, ftsK and tal
      throughout a period of 14 days, indicating viable chlamydiae. Thus, human
      monocyte-derived DC are susceptible to C. pneumoniae infection. These results
      indicate that C. pneumoniae-infected DC can play an important role in the
      transmission of these bacteria in GCA and other chlamydial diseases.

PMID- 16427248
TI  - Cloning from tissue surrogates: antimicrobial peptide (esculentin) cDNAs from the
      defensive skin secretions of Chinese ranid frogs.
AB  - The defensive skin secretions of amphibians are a rich source of bioactive
      peptides. Here we describe a rapid technique for skin granular gland
      transcriptome cloning from a surrogate tissue-the secretion itself. cDNA
      libraries were constructed from lyophilized skin secretion from each of the
      Chinese frogs (Rana schmackeri, Rana versabilis, and Rana plancyi fukienensis)
      using magnetic oligo(dT) bead-captured polyadenylated mRNA as templates. Specific
      esculentin cDNAs were amplified by 3'-RACE using a degenerate primer designed for
      a consensus nucleotide sequence in the 5' untranslated region of previously
      characterized ranid frog peptide cDNAs. The cloned cDNAs were found to encode the
      antimicrobial peptides esculentins 1 and 2 from each of the species examined. The
      presence of predicted peptide structures in skin secretions was confirmed by
      MALDI-TOF mass spectrometry and automated Edman degradation. This experimental
      approach can thus rapidly expedite parallel transcriptome and peptidome analysis
      of amphibian granular gland secretions without harming or sacrificing donor
      animals.

PMID- 16427249
TI  - Thalidomide embryopathy cases in Brazil after 1965.

PMID- 16427250
TI  - Co-consumption of selenium and vitamin E altered the reproductive and
      developmental toxicity of methylmercury in rats.
AB  - Methylmercury (MeHg), an environmental contaminant primarily found in fish and
      seafood, may pose long-term health risks to pregnant women and their developing
      children. The objective of this study was to determine whether co-consumption of
      nutritional supplements would alter the effects of MeHg on reproductive and
      developmental toxicity using a rodent model. Adult female rats were fed a diet
      containing additional selenium (1 ppm), additional vitamin E (225 IU/kg) or a
      combination of the two for 4 weeks before oral dosing of MeHg (1.25 mg/kg/day).
      Treatment with MeHg and dietary supplementation continued throughout pregnancy
      after which the dams were allowed to deliver their offspring. In addition to
      routine evaluations including periodic body weight measurements and daily
      clinical signs observations, dams and pups were evaluated for auditory startle
      habituation and pups were evaluated for developmental landmarks and reflexology.
      The dams and offspring were euthanized approximately 4 weeks after birth of the
      offspring. Results indicated that treatment with MeHg caused adverse effects on
      both reproduction of the dams and decreased progeny survival. However, the dams
      showed significant improvement in body weight gain during lactation and average
      auditory startle response time when the diet was enriched with both selenium and
      vitamin E. The combination of both vitamin E and Se also resulted in a
      significant increase in post-natal survival when compared to MeHg-treated group.
      There was no nutrient effect on the MeHg toxicity shown in offspring physical
      landmarks, performance in reflex tests and assessment of simple auricular startle
      response. Also, accelerated development as indicated by earlier opening in the
      pups of the supplemental diet groups was observed. These results suggest that
      antioxidant nutrients in the diet may alter MeHg reproductive and developmental
      toxicity. The underlying and human health implications warrant further
      investigations.

PMID- 16427251
TI  - The very C-terminus of PRK1/PKN is essential for its activation by RhoA and
      downstream signaling.
AB  - PRK1 is a lipid- and Rho GTPase-activated serine/threonine protein kinase
      implicated in the regulation of receptor trafficking, cytoskeletal dynamics and
      tumorigenesis. Although Rho binding has been mapped to the HR1 region in the
      regulatory domain of PRK1, the mechanism involved in the control of PRK1
      activation following Rho binding is poorly understood. We now provide the first
      evidence that the very C-terminus beyond the hydrophobic motif in PRK1 is
      essential for the activation of this kinase by RhoA. Deletion of the HR1 region
      did not completely abolish the binding of PRK1-DeltaHR1 to GTPgammaS-RhoA nor the
      activation of this mutant by GTPgammaS-RhoA in vitro. In contrast, removing of
      the last six amino acid residues from the C-terminus of PRK1 or truncating of a
      single C-terminal residue from PRK1-DeltaHR1 completely abrogated the activation
      of these mutants by RhoA both in vitro and in vivo. The critical dependence of
      the very C-terminus of PRK1 on the signaling downstream of RhoA was further
      demonstrated by the failure of the PRK1 mutant lacking its six C-terminal
      residues to augment lisophosphatidic acid-elicited neurite retraction in neuronal
      cells. Thus, we show that the HR1 region is necessary but not sufficient in
      eliciting a full activation of PRK1 upon binding of RhoA. Instead, such
      activation is controlled by the very C-terminus of PRK1. Our results also suggest
      that the very C-terminus of PRK1, which is the least conserved among members of
      the protein kinase C superfamily, is a potential drug target for pharmacological
      intervention of RhoA-mediated signaling pathways.

PMID- 16427253
TI  - International academy for oral and facial rehabilitation--Consensus Report.

PMID- 16427252
TI  - Electrosonographic characteristics of sounds from temporomandibular joint disc
      replacement.
AB  - The purpose of this study was to investigate the waveform and electrosonographic
      characteristics of sounds emanating from internal derangement of the
      temporomandibular joint (TMJ). TMJ sounds were recorded from 10 joints of normal
      people (NP), 10 joints from patients with anterior disc displacement with
      reduction (DDR) and 20 joints from patients with anterior disc displacement
      without reduction (DDNR). The sounds were analyzed through fast Fourier transfer
      methods to observe their waveforms and electrosonographic characteristics. The
      observations were then used in differentially diagnosing internal derangement.
      Wave pattern and electrosonography (ESG) differed among the NP, DDR and DDNR
      groups. There was very little difference in frequency between the sounds from DDR
      and DDNR, but the amplitude of the DDR sounds was higher than those of DDNR and
      NP. The sensitivity and specificity of ESG diagnosis for DDR were 77.2% and
      93.3%, respectively, while for DDNR they were 81.6% and 64.7%, respectively.

PMID- 16427254
TI  - DNA microarray detection of antimicrobial resistance genes in diverse bacteria.
AB  - High throughput genotyping is essential for studying the spread of multiple
      antimicrobial resistance. A test oligonucleotide microarray designed to detect 94
      antimicrobial resistance genes was constructed and successfully used to identify
      antimicrobial resistance genes in control strains. The microarray was then used
      to assay 51 distantly related bacteria, including Gram-negative and Gram-positive
      isolates, resulting in the identification of 61 different antimicrobial
      resistance genes in these bacteria. These results were consistent with their
      known gene content and resistance phenotypes. Microarray results were confirmed
      by polymerase chain reaction and Southern blot analysis. These results
      demonstrate that this approach could be used to construct a microarray to detect
      all sequenced antimicrobial resistance genes in nearly all bacteria.

PMID- 16427255
TI  - Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT
      allele with obsessive-compulsive disorder in males.
AB  - BACKGROUND: Mounting evidence suggests the involvement of the dopamine system in
      the pathophysiology of obsessive-compulsive disorder. METHOD: The relationship of
      the dopamine D(2) receptor (DRD2) TaqI A, and catechol-O-methyl-transferase
      (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder
      (OCD) was examined in a sample of 150 patients and 150 controls. RESULTS: OCD
      patients did not show significant differences in genotype distribution and allele
      frequency for polymorphisms investigated relative to controls. However, when the
      sample was stratified by gender, there was a trend to a significant predominance
      of the DRD2 A2A2 genotype (p=0.049), and a higher frequency of the DRD2 A2 allele
      (p=0.020) and low-activity COMT allele (p=0.035) in male OCD patients compared to
      male controls. In addition, we observed an association of the DRD2 A2A2 genotype
      in patients with an early onset of disease (<or=15 years) (p=0.033). CONCLUSIONS:
      Our findings replicate previous reports and provide support for a potential role
      of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

PMID- 16427256
TI  - The early stages of Saccharomyces cerevisiae yeast suspensions damage in moderate
      pulsed electric fields.
AB  - The objectives of this study were to investigate the effects of pulsed electric
      fields (PEF) application to colloidal suspension of Saccharomyces cerevisiae. The
      electrical conductivity measurements during the PEF-treatment of S. cerevisiae
      suspensions were used to monitor the extent of cell damages in the intervals of
      electric field strength E = 3-15 kV/cm and time of PEF treatment t(PEF) = 10(-4)
      to 1s. At relatively small fields (E < 7.5 kV/cm) the early stages of yeast cells
      damages were observed. At such treatment conditions, the damage was incomplete
      and developed at long time of PEF treatment, below the value of E = 7.5 kV/cm
      which is commonly referred in literature as a threshold for this culture. Data
      obtained for the disintegration in conductivity experiments were found in good
      correlation with direct counting of yeast lethality using light microscopy. The
      PEF-induced lethality of the yeast cells and size flocs increased with the mixing
      of suspensions and the increase of temperature.

PMID- 16427257
TI  - Neural networks for longitudinal studies in Alzheimer's disease.
AB  - OBJECTIVE: Alzheimer's disease affects a growing population of elderly people
      today. The predictions about the course of the disease is a key component of
      health care decision making for patients with Alzheimer's. The physician's
      prognosis and predicted trajectory of cognitive decline often form the basis of
      treatment and health care decisions taken by patients and their families. These
      predictions are difficult to make because of the high variability and non
      linearity exhibited by individual patterns of cognitive decline. This paper
      presents a new method of predicting the course of a disease using longitudinal
      data collected through multiple clinic visits. Longitudinal databases are similar
      to temporal databases, with some important differences--data is collected at
      irregular time intervals that are patient specific and also a varying number of
      observations are made for each patient, depending upon the number of times the
      patient visited the clinic. We propose a new type of neural network called the
      mixed effects neural network (MENN) model that can incorporate this type of
      longitudinal information. MATERIAL AND METHODS: We have used longitudinal data on
      704 subjects enrolled at the Layton aging and research center (LAARC) at Oregon
      Health and Science University. A back-propagation algorithm, modified for
      longitudinal data is used to obtain the weight parameters of the MENN. The
      modified back-propagation algorithm is further embedded in an iterative procedure
      that estimates the noise variance and the parameters that capture the
      longitudinal (temporal) correlation structure. RESULTS: We have compared the
      performance of the MENN with linear mixed effects models and standard neural
      networks (NN). MENN show better performance (misclassification rate = 0.13 and
      relative MSE = 0.35) as compared to standard NN (misclassification rate = 0.34
      and relative MSE = 2.74) and linear mixed effects models (misclassification rate
      = 0.14 and relative MSE = 0.4). CONCLUSION: The results show that this method can
      be a useful tool for predicting non-linear disease trajectories and uncovering
      significant prognostic factors in longitudinal databases.

PMID- 16427258
TI  - Subcutaneous microchip-associated tumours in B6C3F1 mice: a retrospective study
      to attempt to determine their histogenesis.
AB  - Fifty-two subcutaneous tumours associated with microchip were collected from
      three carcinogenicity B6C3F1 mice studies. Two of these 52 tumours were
      adenocarcinoma of the mammary gland located on the dorsal region forming around
      the chip. All the other 50 were mesenchymal in origin and were difficult to
      classify on morphological grounds with haematoxylin-eosin. These sarcomas were
      investigated using a panel of immunohistochemistry and special stains consisting
      of desmin, smooth muscle actin (SMA), myogenin, S100, mouse macrophages,
      phosphotungstic acid haematoxylin (PTAH) and Masson's trichrome (MT). All the
      sarcomas displayed the same histochemical characteristics and a close
      immunophenotype, characterized by desmin +/-, SMA+, myogenin--, S100--, mouse
      macrophages + and PTAH-. These tumours thus appear to have similar histologic
      type lineage and designation as sarcomas not otherwise specified (NOS) with a
      large myofibroblastic component appears today to be more appropriate and it is
      likely to clarify them in the future with the emergence of new markers.

PMID- 16427259
TI  - Multifactorial aspects of antimicrobial activity of propolis.
AB  - We investigated the antibacterial activity of sub-inhibitory concentrations of
      ethanolic extract of propolis (EEP), and its effect on the antibacterial activity
      of some antibiotics. Some clinically isolated Gram-positive strains were used.
      Moreover, sub-inhibitory concentrations of EEP were used to value its action on
      some important virulence factors like lipase and coagulase enzymes, and on
      biofilm formation in Staphylococcus aureus. Our results indicated that EEP had a
      significant antimicrobial activity towards all tested clinical strains. Adding
      EEP to antibacterial tested drugs, it drastically increased the antimicrobial
      effect of ampicillin, gentamycin and streptomycin, moderately the one of
      chloramphenicol, ceftriaxon and vancomycin, while there was no effect with
      erithromycin. Moreover, our results pointed out an inhibitory action of EEP on
      lipase activity of 18 Staphylococcus spp. strains and an inhibitory effect on
      coagulase of 11 S. aureus tested strains. The same EEP concentrations showed a
      negative interaction with adhesion and consequent biofilm formation in S. aureus
      ATCC 6538P.

PMID- 16427260
TI  - Determination of laccase gene expression during degradation of 2,4,6
      trinitrotoluene and its catabolic intermediates in Trametes versicolor.
AB  - We have cloned a laccase gene fragment isolated from a Trametes versicolor strain
      in Korea. It showed high similarity in nucleotide sequences when compared with
      other fungal laccases. TNT (2,4,6-trinitrotoluene), a widely used explosive, was
      transformed rapidly by T. versicolor. When TNT and its catabolic intermediates
      were added to the fungal culture, they were transformed during the first few
      hours and the expression level of the laccase gene was increased during the early
      stage of cultivation.

PMID- 16427261
TI  - Production and partial characterization of bacteriocin-like pepitdes by Bacillus
      licheniformis ZJU12.
AB  - Bacillus licheniformis ZJU12, which was isolated from soil, could produce
      bacteriocin-like peptides that exhibited a broad spectrum of antagonistic
      activity against various species of Gram-positive bacteria and fungal pathogens,
      but not against Gram-negative bacteria tested except Xanthomonas oryzae pv.
      oryzae, a rice pathogen. The bacteriocin-like peptides were sensitive to
      proteinase K and trypsin. The activity was stable during temperature exposure up
      to 100 degrees C for 30 min, but lost completely at 121 degrees C for 15 min. The
      cell-free supernatant of B. licheniformis ZJU12 was shown to retain the activity
      within the pH range of 2-9, and the optimum pH for the activity was about 6.5. No
      adverse effect of the antagonistic compound to mice was observed in acute
      toxicity tests with the dose of 0.8 mg/20 g.

PMID- 16427262
TI  - Antiviral property and mechanisms of a sulphated polysaccharide from the brown
      alga Sargassum patens against Herpes simplex virus type 1.
AB  - A sulphated polysaccharide (SP-2a) from the brown alga Sargassum patens (Kutz.)
      Agardh (Sargassaceae) was found to significantly inhibit the in vitro replication
      of both the acyclovir (ACV)-sensitive and -resistant strains of Herpes simplex
      virus type 1 (HSV-1), in dose-dependent manners, with 50% inhibitions occurring
      with 1.5-5.3 microg/ml of the polysaccharide. SP-2a exhibited extracellular
      virucidal activity only against the ACV-sensitive strains, but not the resistant
      strain, at the concentration of 100 microg/ml. The strongest antiviral activities
      against the different strains of HSV-1 were observed when this polysaccharide was
      present during and after adsorption of the virus to host cells. The inhibitory
      effect of SP-2a on virus adsorption occurred dose-dependently in all the HSV-1
      strains tested, and the adsorption of the ACV-resistant DM2.1 strain was reduced
      by 81.9% (relative to control) with 4 microg/ml of the polysaccharide. This study
      clearly demonstrated that the antiviral mode of action of SP-2a is mediated
      mainly by inhibiting virus attachment to host cells, and this sulphated
      polysaccharide might have different modes of action against the ACV-sensitive and
      -resistant strains of HSV-1.

PMID- 16427263
TI  - The presence of natural human antibodies reactive against pharmacologically
      active pectic polysaccharides from herbal medicines.
AB  - Direct ELISA was performed using normal human sera and human colostrum, to
      analyse the presence of antibodies which react with pharmacologically active
      pectic polysaccharides isolated from plants used in traditional Japanese herbal
      (Kampo) medicine. All sera and colostrum were shown to contain IgM, IgG, IgA and
      secretory IgA class antibodies which react with the active pectic polysaccharides
      to different degrees. The reacting IgG antibody in normal human serum recognized
      the ramified regions (rhamnogalacturonan core with carbohydrate side-chains) of
      the pharmacologically active pectic polysaccharides as the active sites for
      complement-activating activity. Correlation analysis indicated that a significant
      and positive correlation was observed between reactivity with the reacting
      antibody of IgG class and the degree of complement-activating activity of the
      active polysaccharides. The reacting IgG class antibody, which was purified from
      normal human serum by affinity chromatography on bupleuran 2IIc (a
      pharmacologically active pectic polysaccharide from the roots of Bupleurum
      falcatum)-immobilized Sepharose, showed cross-reactivity not only with some other
      pharmacologically active pectic polysaccharides from other medicinal herbs but
      also with autoantigens such as single-strand DNA, myosin and tublin from mammals.

PMID- 16427264
TI  - Upregulation of PBR mRNA expression in human neuroblastoma cells by flavonoids.
AB  - To investigate the putative mediation of peripheral benzodiazepine receptor (PBR)
      in the cytotoxicity of flavonoids, in this study, modulatory effects of several
      flavonoids on the lipid peroxide (LPO) production and PBR mRNA expression of
      human neuroblastoma cells were observed. Elevated levels of peroxidated products
      in cancer cells may activate pro-apoptotic and anti-proliferative signaling
      pathways. Treatment of 10(-6) M 4'-chlorodiazepam and PK 11195 ligands of the PBR
      for 6 days enhanced the generation of LPO of the human neuroblastoma cells.
      Several flavonoids, well-known cytotoxic substances, potentiated the enhancement
      of LPO production by PBR ligands. Treatment of 10(-6) M flavonoids for 6 days
      elevated the expression of PBR mRNA in cells. These findings indicate that the
      potential of flavonoids to induce apoptosis in cancer cells is strongly
      associated with their PBR-inducing properties, thereby providing a new mechanism
      by which polyphenolic compounds may exert their cancer-preventive and anti
      neoplastic effects.

PMID- 16427265
TI  - D-dimer levels in pleural effusions.
AB  - INTRODUCTION: D-dimer is a degradation product of cross-linked fibrin. We
      hypothesized that hemorrhagic pleural effusions would have greater D-dimer levels
      than non-hemorrhagic pleural effusions, and that persistently bloody effusions
      would be distinguishable from thoracentesis-induced bloody effusions by the D
      dimer level. METHODS: Forty pleural effusions were studied. D-dimer levels
      (measured by ELISA), red blood cell (RBC) count, white blood cell (WBC) count,
      lactate dehydrogenase (LDH), and protein level was measured for each effusion.
      Ten effusions, five non-bloody, and five bloody were studied for each of the
      following disease states: parapneumonic effusion, congestive heart failure, post
      coronary artery bypass grafting, and lung cancer. RESULTS: No significant
      difference of the D-dimer level was noted between bloody and non-bloody effusions
      of different disease states (P=0.286). There was no significant difference in the
      median D-dimer levels between all the bloody and all the non-bloody effusions
      (P=0.88). There was no significant difference (P=0.51) in D-dimer levels between
      five diseases groups when the bloody and non-bloody fluids were combined. The D
      dimer levels did not correlate with the RBC count (r=0.11, P=0.48), WBC count
      (r=0.13, P=0.53), LDH (r=0.01, P=0.93), or protein levels (r=-0.01, P=0.93) in
      any of the groups. CONCLUSION: Measurement of pleural fluid D-dimer levels does
      not distinguish persistently bloody effusions from non-bloody effusions, and does
      not aid in narrowing the differential diagnosis of an effusion.

PMID- 16427266
TI  - Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of
      persistent asthma.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and safety of once
      daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid,
      with once-daily budesonide in persistent asthma. METHODS: Eligible patients
      requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to
      400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a
      2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece,
      equivalent to 1600 microg/day). Patients with an increase in forced expiratory
      volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex
      actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose
      inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the
      morning for 12 weeks. Change in FEV1 was the primary endpoint. RESULTS: In all,
      359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased
      by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L
      in the budesonide group. For FEV1, ciclesonide was noninferior and numerically
      superior to budesonide. For FVC, ciclesonide was statistically superior to
      budesonide (P=0.010). Asthma symptom scores were comparable; the median
      percentage of symptom-free days was significantly higher for ciclesonide (43.6%)
      versus budesonide (25.8%) (P=0.017). Rescue medication use decreased
      significantly only for ciclesonide patients (P=0.009). Frequency of adverse
      events was low in both groups. CONCLUSION: Ciclesonide 320 microg once daily by
      HFA-MDI without a spacer was at least as effective as budesonide 320 microg once
      daily in persistent asthma.

PMID- 16427267
TI  - The characterization of waste cathode-ray tube glass.
AB  - New re-use applications are needed to address the relatively large quantity of
      waste electronic products generated in the world. Cathode-ray tubes (CRTs) from
      computer monitors and TV sets are a large component of such waste. The three
      glass components of CRTs are the funnel, panel and neck, which are produced by
      various manufacturers and are now collected by asset-recovery centres. In this
      paper, we characterize waste funnel and panel glass from dismantled cathode-ray
      tubes with a view to assisting the development of new re-use applications. The
      heavy metal (lead, barium, and strontium) content of such glass represents an
      acute risk to the environment. Our results of the chemical composition for
      different kinds of waste CRT glass including black & white and color CRTs show
      that CRT glass from different producers have generally similar chemical
      compositions. In particular, the compositions of funnel and panel black & white
      CRT glass are similar, but are different to those of panel and funnel color CRT
      glass. We also measured the following specific properties of each type of CRT
      glass: density, glass transition temperature, and linear coefficient of thermal
      expansion. It was found that the coefficients of thermal expansion of CRT glass
      do not vary with their composition. In contrast, the measured densities and glass
      transition temperatures do vary with composition. On the basis of our
      experimental data and data found in the literature, we outline the main
      properties of several waste CRT glass currently in circulation. The aim of this
      study was to provide the data required to determine if this kind of waste could
      be entirely (or partially) re-used and to aid the search for promising methods of
      treatment.

PMID- 16427268
TI  - Cell-cell interactions in synaptogenesis.
AB  - Synaptogenesis is a finely organized process, intriguing in its precise temporal
      and spatial resolution. It occurs as the dendrite of a postsynaptic neuron and an
      incoming axon communicate at defined sites to establish a stable synapse
      together. The molecular cues that guide synaptogenesis are now beginning to be
      identified, and cell surface interactions at synaptic sites participate
      prominently in the key steps. Interactions include trans-synaptic adhesion of pre
      and post-synaptic neurons but also binding to non-neuronal neighboring cells and
      the extracellular matrix. These signals recruit scaffolding molecules, other
      adhesion molecules, and neurotransmitter receptors to bring together the key
      components of functional synapses. Recent progress provides stimulating insights
      into the role of adhesion and signaling molecules in the formation and function
      of synaptic specializations.

PMID- 16427269
TI  - Synapse formation and plasticity: recent insights from the perspective of the
      ubiquitin proteasome system.
AB  - The formation of synaptic connections during the development of the nervous
      system requires the precise targeting of presynaptic and postsynaptic
      compartments. Furthermore, synapses are continually modified in the brain by
      experience. Recently, the ubiquitin proteasome system has emerged as a key
      regulator of synaptic development and function. The modification of proteins by
      ubiquitin, and in many cases their subsequent proteasomal degradation, has proven
      to be an important mechanism to control protein stability, activity and
      localization at synapses. Recent work has highlighted key questions of the UPS
      during the development and remodeling of synaptic connections in the nervous
      system.

PMID- 16427270
TI  - Photolyases and cryptochromes: common mechanisms of DNA repair and light-driven
      signaling?
AB  - DNA photolyases are extremely efficient light-driven DNA repair enzymes that use
      the energy of a blue-light photon to 'inject' an electron onto UV-damaged DNA,
      catalyzing the splitting of mutagenic pyrimidine dimers. By contrast,
      cryptochromes use blue light to trigger signaling cascades in multicellular
      organisms, fungi and several prokaryotes. Despite these functional differences,
      both protein families arose from a common ancestor and share many similarities,
      such as the overall protein fold, the presence of antenna chromophores and the
      use of flavin adenine dinucleotide (FAD) as the primary reactive group. Several
      significant advances in the biophysical and structural characterization of
      photolyases and cryptochromes are now revealing the details of how light-driven
      redox reactions can be used for such seemingly different purposes.

PMID- 16427271
TI  - Structural basis of HutP-mediated transcription anti-termination.
AB  - Bacteria often use anti-terminator proteins to sense a specific metabolite signal
      and direct RNA polymerase to either terminate transcription or transcribe the
      downstream genes of an operon. Although many proteins that regulate various
      operons using this mechanism have been identified, insights into their activation
      processes before cognate mRNA binding have remained obscure. HutP from Bacillus
      subtilis regulates the hut operon by an anti-termination mechanism. Recently,
      several crystal structures of HutP [apo-HutP, HutP-L-histidine (and histidine
      analog), HutP-L-histidine-Mg(2+) and HutP-L-histidine-Mg(2+)-RNA] have been
      reported. These structural and functional studies of HutP have revealed how the
      protein undergoes conformational changes in response to two key components: L
      histidine and Mg(2+) ions.

PMID- 16427273
TI  - Experimental and kinetic studies on methylene blue adsorption by coir pith
      carbon.
AB  - Varying the parameters such as agitation time, dye concentration, adsorbent dose,
      pH and temperature carried out the potential feasibility of thermally activated
      coir pith carbon prepared from coconut husk for removal of methylene blue.
      Greater percentage of dye was removed with decrease in the initial concentration
      of dye and increase in amount of adsorbent used. Kinetic study showed that the
      adsorption of dye on coir pith carbon was a gradual process. Lagergren first
      order, second-order, intra particle diffusion model and Bangham were used to fit
      the experimental data. Equilibrium isotherms were analysed by Langmuir,
      Freundlich, Dubnin-Radushkevich, and Tempkin isotherm. The adsorption capacity
      was found to be 5.87 mg/g by Langmuir isotherm for the particle size 250-500
      microm. The equilibrium time was found to be 30 and 60 min for 10 and 20 mg/L and
      100 min for 30, 40 mg/L dye concentrations, respectively. A maximum removal of
      97% was obtained at natural pH 6.9 for an adsorbent dose of 100 mg/50 mL and 100%
      removal was obtained for an adsorbent dose of 600 mg/50 mL of 10 mg/L dye
      concentration. The pH effect and desorption studies suggest that chemisorption
      might be the major mode of the adsorption process. The change in entropy
      (DeltaS0) and heat of adsorption (DeltaH0) of coir pith carbon was estimated as
      117.20 J/mol/K and 30.88 kJ/mol, respectively. The high negative value of change
      in Gibbs free energy indicates the feasible and spontaneous adsorption of
      methylene blue on coir pith carbon.

PMID- 16427272
TI  - Effects of down-regulating the Id genes in human colorectal cancer cells on early
      steps of haematogenous metastasis.
AB  - Id genes (inhibitor of DNA binding/differentiation) play important roles in
      tumour growth. We have previously described crucial roles of Id gene over
      expression in endothelial cells for tumour angiogenesis. Here, we have evaluated
      direct effects of Id gene down-regulation on tumour cells, namely on cell
      proliferation, motility, and adhesion to lung microvasculature during
      haematogenous metastasis. For this purpose, Id genes were stably down-regulated
      by RNA interference in human colorectal cancer cells. These cells showed delayed
      proliferation, inhibited motility and decreased expression of integrin alpha6 and
      consequently reduced adhesion to lung microvasculature in mice. Static adhesion
      assays and laminar flow assays revealed decreased laminin binding capacity of
      these cells, and blocking experiments confirmed that it could be attributed to
      decreased expression of integrin alpha6. The present results indicate important
      roles of Id genes in tumour cells during early steps of haematogenous metastasis
      and suggest dual effects from their therapeutic inhibition.

PMID- 16427274
TI  - Ferulic acid esterase production by Streptomyces sp.
AB  - Studies were carried out on ferulic acid esterase production using a culture of
      Streptomyces S10. In optimized condition, enzyme yield was 2.0 mU/ml in MBS
      medium, containing 1.5% de-starched wheat bran at 30 degrees C and initial pH 6.5
      under agitated submerged culture.

PMID- 16427275
TI  - Effect of water deficit on microbial characteristics in soil amended with sewage
      sludge or inorganic fertilizer under laboratory conditions.
AB  - The potential impact of different types of organic (sewage sludge) or inorganic
      (mineral fertilizer) amendments to a basic soil was investigated under dry
      conditions. A soil incubation experiment was carried out over 64 days; there were
      two fertility treatments: sewage sludge (SS) (140 t ha(-1)), mineral fertilizer
      (M) and an unamended control (C). Two levels of irrigation were imposed: (1) well
      watered, kept at 60% of its water holding capacity, and (2) water-deficit at 6%.
      Available N-NO3-, N-NH4+ and P, and electrical conductivity (EC) increased in SS
      and M-treated soils. Under well-watered conditions activities of some enzymes
      (protease-BAA, phosphatase and beta-glucosidase), and microbiological properties
      (microbial biomass carbon, basal respiration and dehydrogenase activity) were
      stimulated in SS-treated soils. Under water-deficit conditions, protease-BAA,
      phosphatase and beta-glucosidase activities, and basal respiration were more
      reduced in SS than in C and M. Results showed that under severe dry conditions,
      soil microbial activity always remained higher in organic amended soils than when
      mineral fertilizer was added.

PMID- 16427276
TI  - Effect of low initial C/N ratio on aerobic composting of swine manure with rice
      straw.
AB  - Two pilot composting experiments were conducted to investigate the effect of low
      initial C/N ratio on the composting of swine manure with rice straw by measuring
      physical and chemical parameters. The results showed that the thermophilic
      duration of bin 1 and bin 2 was long enough to satisfy the sanitary standard, and
      swine manure could reach maturity. Bin 1 containing larger amount of swine manure
      and less amount of rice straw showed a higher nitrogen loss (8%), shorter
      thermophilic phase, and longer maturity time (about 2 weeks) than bin 2. However,
      economical analysis showed a lower initial C/N ratio (20) could reduce 172 kg
      rice straw per ton fresh swine manure than a higher C/N ratio (25), and more
      swine manure could also be treated. Therefore, a low initial C/N ratio (20) could
      be suggested in the composting of swine manure with rice straw.

PMID- 16427277
TI  - Microbial and plant derived biomass for removal of heavy metals from wastewater.
AB  - Discharge of heavy metals from metal processing industries is known to have
      adverse effects on the environment. Conventional treatment technologies for
      removal of heavy metals from aqueous solution are not economical and generate
      huge quantity of toxic chemical sludge. Biosorption of heavy metals by
      metabolically inactive non-living biomass of microbial or plant origin is an
      innovative and alternative technology for removal of these pollutants from
      aqueous solution. Due to unique chemical composition biomass sequesters metal
      ions by forming metal complexes from solution and obviates the necessity to
      maintain special growth-supporting conditions. Biomass of Aspergillus niger,
      Penicillium chrysogenum, Rhizopus nigricans, Ascophyllum nodosum, Sargassum
      natans, Chlorella fusca, Oscillatoria anguistissima, Bacillus firmus and
      Streptomyces sp. have highest metal adsorption capacities ranging from 5 to 641
      mg g(-1) mainly for Pb, Zn, Cd, Cr, Cu and Ni. Biomass generated as a by-product
      of fermentative processes offers great potential for adopting an economical metal
      recovery system. The purpose of this paper is to review the available information
      on various attributes of utilization of microbial and plant derived biomass and
      explores the possibility of exploiting them for heavy metal remediation.

PMID- 16427278
TI  - Fabrication and application of neoglycolipid arrays in a microtiter plate.
AB  - The work presented herein is a new noncovalent glycoarray assembly method for
      microplates created by simply mixing together a carbohydrate and a
      tetradecylamine. Alpha-mannose was utilized in the model study and product
      formation was detected by lectin binding. The method can be further extended to
      array complex carbohydrates.

PMID- 16427279
TI  - Design and modular parallel synthesis of a MCR derived alpha-helix mimetic
      protein-protein interaction inhibitor scaffold.
AB  - A terphenyl alpha-helix mimetic scaffold recognized to be capable of disrupting
      protein-protein interactions was structurally morphed into an easily amenable and
      versatile multicomponent reaction (MCR) backbone. The design, modular in-parallel
      library synthesis, initial cell based biological data, and preliminary in vitro
      screening for the disruption of the Bcl-w/Bak protein-protein interaction by
      representatives of the MCR derived scaffold are presented.

PMID- 16427280
TI  - Carriers and patients with muscle-eye-brain disease can be rapidly diagnosed by
      enzymatic analysis of fibroblasts and lymphoblasts.
AB  - We report a new fibroblast and lymphoblast based protein O-mannosyl beta-1,2-N
      acetylglucosaminyltransferase 1 enzymatic assay, which allows rapid and accurate
      diagnosis of carriers and patients with muscle-eye-brain type of congenital
      muscular dystrophy. Seven patients with genetically confirmed muscle-eye-brain
      disease were assayed for protein O-mannosyl beta-1,2-N
      acetylglucosaminyltransferase 1 enzyme activity. In three patients and their
      heterozygous parents, the assays were done on EBV-transformed lymphoblasts, in
      another three patients they were done on cultured fibroblasts and in the last
      patient on both fibroblasts and lymphoblasts. Cultured fibroblasts and
      lymphoblasts from the muscle-eye-brain patients showed a highly significant
      decrease in protein O-mannosyl beta-1,2-N-acetylglucosaminyltransferase 1
      activity relative to controls. The residual protein O-mannosyl beta-1,2-N
      acetylglucosaminyltransferase 1 level in fibroblasts (average 0.11 nmoles/h per
      mg) was about 13% of normal controls. The ratio of protein O-mannosyl beta-1,2-N
      acetylglucosaminyltransferase 1 activity to the activity of a glycosyltransferase
      control (N-acetylglucosaminyltransferase 1; GnT1) in fibroblasts was on average
      0.006 in muscle-eye-brain patients and 0.045 in controls. The average residual
      protein O-mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 level in
      lymphoblasts was 15% of normal controls. The average ratio of protein O-mannosyl
      beta-1,2-N-acetylglucosaminyltransferase 1/GnT1 activity was 0.007 in muscle-eye
      brain patients, 0.026 in heterozygous carriers and 0.046 in normal controls.
      Assay of protein O-mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 activity
      in fibroblasts and lymphoblasts from muscle-eye-brain carriers and patients
      provides a rapid and relatively simple diagnostic test for this disease and could
      be used as a screening test in carriers and patients with complex congenital
      muscular dystrophy.

PMID- 16427281
TI  - BSCL2 mutations in two Dutch families with overlapping Silver syndrome-distal
      hereditary motor neuropathy.
AB  - Mutations in the BSCL2 gene have recently been identified in families with (SPG17
      linked) Silver syndrome-type hereditary spastic paraparesis as well as in
      families with distal hereditary motor neuropathy (HMN). We describe the first two
      Dutch families with BSCL2 mutations and corroborate the phenotypic variability of
      this gene mutation, as features compatible with Silver syndrome, variant Silver
      syndrome (with predominant foot rather than hand muscle involvement), distal HMN
      type II, or distal HMN type V were all encountered.

PMID- 16427282
TI  - Autosomal dominant nemaline myopathy with intranuclear rods due to mutation of
      the skeletal muscle ACTA1 gene: clinical and pathological variability within a
      kindred.
AB  - Nemaline Myopathy with Intranuclear Rods is a rare variant of nemaline myopathy,
      due in almost all instances to mutation of ACTA1, the gene encoding skeletal
      muscle alpha-actin. We describe the novel autosomal dominant occurrence in a
      three-generation kindred, and review previously reported cases. Onset of
      myopathic symptoms in our kindred was in infancy or early childhood. Beyond
      infancy, limb muscle weakness was non-disabling and minimally progressive. A tall
      thin face and facial myopathy were prominent features in the affected adults. By
      light microscopy, muscle biopsies ranged from almost normal, to chronic myopathy
      with sarcoplasmic and intranuclear rods. A heterozygous GTG-ATG mutation
      (Val163Met) was found in exon 4 of ACTA1 in affected individuals. Actin is
      normally present within the nucleus in only trace amounts. Mutation at postion
      163 may result in intranuclear rods by virtue of its close proximity to a nuclear
      export signal within the actin molecule.

PMID- 16427283
TI  - Predictive value of serum anti-C1q antibody levels in experimental autoimmune
      myasthenia gravis.
AB  - Components of the complement cascade and circulating immune complexes play
      important roles in both experimental autoimmune myasthenia gravis and myasthenia
      gravis in humans. Thus far, no serological factor has been identified to predict
      the clinical severity of either myasthenia gravis. Upon immunization with
      acetylcholine receptor, levels of complement factors C1q, C3 and CIC increase
      with time in sera from C57BL/6 (B6) mice. Both these and plasma samples from
      myasthenia gravis patients also contain anti-C1q antibodies. The serum levels of
      anti-C1q antibodies but not C1q, C3 and CIC are significantly correlated with the
      clinical severity in the experimental myasthenia mice. However, this correlation
      is not observed in myasthenia gravis patients.

PMID- 16427284
TI  - Health related quality of life in people with hereditary neuromuscular diseases:
      an investigation of test-retest agreement with comparison between two generic
      questionnaires, the Nottingham health profile and the short form-36 items.
AB  - The present work attempts to define reproducibility, test-retest and internal
      consistencies of two standardised tools that measure health related quality of
      life (HRQoL), specifically as they apply to hereditary neuromuscular disease
      (HNMD): the Nottingham health profile (NHP) and the medical outcome study 36-item
      short-form questionnaire (MOS SF-36). A cross sectional survey of 108 hereditary
      neuromuscular disease patients completed the questionnaires consecutively in the
      course of multidisciplinary consultations in Reims between April 2002 and
      February 2005. The results of the study confirm the acceptability of using
      generic questionnaires such as the Nottingham health profile and the SF-36, and
      show good reliability for these instruments. For both instruments,
      reproducibility (test-retest) appears excellent for the physical dimensions
      explored, and satisfactory for the mental dimensions. There is nonetheless a need
      for health related quality of life measures validated for neuromuscular disease
      patients. Health related quality-of-life (HRQoL) measures provide information on
      how patients assess their health and the care provision they are offered.

PMID- 16427285
TI  - Brachial plexus hypertrophy in chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - We present the clinical, imaging and neuropathological findings in three patients
      with predominant brachial plexus neuropathy. MR scanning was key to determining
      the brachial plexus involvement. Biopsy of the brachial plexus was performed in
      one patient. The appearances of the brachial plexus on MRI, in conjunction with
      the clinical presentations of these patients, suggest that they are unusual
      variants within the spectrum of chronic inflammatory demyelinating
      polyradiculoneuropathy.

PMID- 16427287
TI  - Accelerometry based assessment of gait parameters in children.
AB  - The objective of this study was to examine if spatio-temporal gait parameters in
      healthy children can be determined from accelerations measured at the lower trunk
      as has been demonstrated in adults, previously. Twenty children aged 3-16 years,
      participated in a protocol that involved repeated walks of different distances in
      an indoor environment. During walking, accelerations were measured by three
      orthogonally mounted acceleration sensors in a small wireless device (DynaPort
      MiniMod) that was attached to the lower back. Based on an inverted pendulum
      approach, spatio-temporal gait parameters and walking distances were computed
      from the acceleration signals. Results were compared to video observations and
      known walking distances and durations. Steps were successfully detected in 99.6+/
      0.6% of all observed steps (n=5554). On average, walking distance was accurately
      estimated (100.6+/-3.3%, range 93-106.7%). No correlation was found between the
      number of miscounted steps and the total number of steps or the age of the
      subject. It can be concluded that the use of an inverted pendulum model provides
      the possibility to estimate spatio-temporal gait parameters in children as well
      as in adults. The method allows an inexpensive and comfortable assessment of gait
      parameters in children, is applicable in controlled, indoor environments and
      could be tested for applicability under free living conditions.

PMID- 16427286
TI  - Service provision for adults with long-term disability: a review of services for
      adults with chronic neuromuscular conditions in the United Kingdom.
AB  - The purpose of the study is to determine the level of service provision for
      adults with neuromuscular disease in the United Kingdom. The method is
      questionnaire survey of clinicians running specialist clinics for adults with
      NMD. Specialist services are mostly concentrated in areas of high population
      density with rural areas being less well served. Access to specialist clinical
      services is generally good, although funding for respiratory support is erratic.
      Joint paediatric/adult or adolescent clinics are relatively uncommon.
      Availability of therapists with an interest in muscular disease is variable.
      There are long waiting times for powered wheelchairs in many areas. Provision of
      disabled parking spaces was thought to be inadequate in most hospitals. Current
      service provision is inadequate to meet the complex needs of this patient
      population in the UK. Particular areas of concern are the transfer of care from
      paediatric to adult services and the availability of experienced therapists.

PMID- 16427288
TI  - A method for analyzing joint symmetry and normalcy, with an application to
      analyzing gait.
AB  - A new method for analyzing symmetry and normalcy of gait patterns is explained.
      This method utilizes eigenvectors to compare waveforms. The right and left limbs
      of a single subject are compared to determine symmetry. To determine normalcy, a
      single limb from a subject is compared to a normative file created from the
      average of healthy control subjects. The analysis method provides four measures
      of symmetry and normalcy: trend phase, trend symmetry/normalcy, range amplitude
      ratio, and range offset. The trend symmetry/normalcy is a comparison of the
      shapes of the waveforms for each limb. The range amplitude ratio is a comparison
      of the range of motion of each limb. The range offset is a comparison of the
      range in which each limb operates. The exact methods and clinical applications
      are provided.

PMID- 16427289
TI  - Antitumor agents 247. New 4-ethoxycarbonylethyl curcumin analogs as potential
      antiandrogenic agents.
AB  - 4-Ethoxycarbonylethyl curcumin (ECECur) (3) is a current drug candidate for the
      treatment of prostate cancer. Due to problems inherent in the tautomerism of
      ECECur, 4-fluoro-4-ethoxycarbonylethyl curcumin (4) and 4-ethoxycarbonylethylenyl
      curcumin (5) were designed and synthesized. These two target compounds and their
      synthetic intermediates (4-9) were evaluated for their inhibitory activity
      against androgen receptor transcription in LNCaP and PC-3 prostate cancer cell
      lines. While the enol-keto analogs showed varying anti-androgen potencies, the di
      keto analogs showed no activity. Tetrahydropyranylation of the phenoxy groups had
      a positive impact on the anti-AR activity of 4-ethoxycarbonylethylenyl curcumin,
      but a negative impact on the activity of ECECur. With potent anti-AR activity, di
      tetrapyranylated 4-ethoxycarbonylethylenyl curcumin (9), which exists in only one
      form, is a good drug lead for further structural modification. Based on the SAR
      information obtained from the above study, five new compounds were designed and
      subsequently synthesized. Among them, compound 10 was found to be the most potent
      anti-AR agent and is considered to be a promising drug candidate for the
      treatment of prostate cancer.

PMID- 16427290
TI  - Synthesis and antibacterial activity of N-[2-[5-(methylthio)thiophen-2-yl]-2
      oxoethyl] and N-[2-[5-(methylthio)thiophen-2-yl]-2
      (oxyimino)ethyl]piperazinylquinolone derivatives.
AB  - A number of N-substituted piperazinylquinolone derivatives were synthesized and
      evaluated for antibacterial activity against Gram-positive and Gram-negative
      bacteria. Preliminary results indicated that most compounds tested in this study
      demonstrated comparable or better activity against Staphylococcus aureus and
      Staphylococcus epidermidis than their parent piperazinylquinolones as reference
      drugs. Among these derivatives, ciprofloxacin derivative 5a, containing N-[2-[5
      (methylthio)thiophen-2-yl]-2-oxoethyl] residue, showed significant improvement of
      potency against staphylococci, maintaining Gram-negative coverage.

PMID- 16427292
TI  - Correction factors for the INER-improved free-air ionization chambers calculated
      with the Monte Carlo method.
AB  - Monte Carlo method was used to simulate the correction factors for electron loss
      and scattered photons for two improved cylindrical free-air ionization chambers
      (FACs) constructed at the Institute of Nuclear Energy Research (INER, Taiwan).
      The method is based on weighting correction factors for mono-energetic photons
      with X-ray spectra. The newly obtained correction factors for the medium-energy
      free-air chamber were compared with the current values, which were based on a
      least-squares fit to experimental data published in the NBS Handbook 64 [Wyckoff,
      H.O., Attix, F.H., 1969. Design of free-air ionization chambers. National Bureau
      Standards Handbook, No. 64. US Government Printing Office, Washington, DC, pp. 1
      16; Chen, W.L., Su, S.H., Su, L.L., Hwang, W.S., 1999. Improved free-air
      ionization chamber for the measurement of X-rays. Metrologia 36, 19-24]. The
      comparison results showed the agreement between the Monte Carlo method and
      experimental data is within 0.22%. In addition, mono-energetic correction factors
      for the low-energy free-air chamber were calculated. Average correction factors
      were then derived for measured and theoretical X-ray spectra at 30-50 kVp.
      Although the measured and calculated spectra differ slightly, the resulting
      differences in the derived correction factors are less than 0.02%.

PMID- 16427291
TI  - Synthesis and activity of a new class of pathway-selective estrogen receptor
      ligands: hydroxybenzoyl-3,4-dihydroquinoxalin-2(1H)-ones.
AB  - The anti-inflammatory activity of non-selective estrogens has been attributed to
      their ability to antagonize the activity of nuclear factor kappaB (NF-kappaB), a
      known mediator of inflammatory responses. Here we report the identification of a
      potent new class of pathway-selective ER ligands that selectively antagonize NF
      kappaB functional activity, while exhibiting a lack of classical estrogenic
      effect.

PMID- 16427293
TI  - An analytical solution for the solid angle subtended by a circular detector for a
      symmetrically positioned linear source.
AB  - The analytical determination of the solid angle subtended by a circular detector
      for a line source in a parallel plane, whose midpoint is co-axial with the
      detector's center, is of some relevance to the medical and nuclear power fields.
      No report has been found in the literature of a closed-form solution to this
      problem. We present a first principles solution to the problem along with a
      graph, which gives some indication of the behavior of the derived expression.

PMID- 16427294
TI  - Determination of HPGe detector response using MCNP5 for 20-150 keV X-rays.
AB  - The Monte Carlo method was used to calculate the efficiency, escape and Compton
      curves of a planar high-purity germanium detector (HPGe) in the 20-150 keV
      energy. These curves were used for the determination of photons spectra produced
      by an X-ray machine in order to allow a precise characterization of photon beams
      applied to medical diagnosis. The detector was modeled with the MCNP5 computer
      code and validated by comparison with experimental data. The air kerma calculated
      after the spectra stripping was compared with ionization chamber measurements.

PMID- 16427295
TI  - Relationship between head posture and hyoid position in adult females and males.
AB  - AIM: The aim of this study was to investigate head posture and hyoid bone
      position using cephalometric radiographs of adults. MATERIAL AND METHODS: The
      material consisted of 76 cephalometric films (38 each male/female) taken at the
      natural head posture. The individuals were over 18 years of age, had parents of
      Turkish origin, an acceptable face structure, ideal dental occlusion, and an ANB
      angle of 1-5 degrees; the dentitions were complete except the third molars and
      there were no visual, hearing, breathing or swallowing disorders. In addition,
      the subjects had not undergone orthodontic treatment or orthognathic surgery, had
      no burns, injuries, or scars in the head and neck regions. In order to determine
      the natural head position, the subjects were asked to stand in a relaxed manner
      (the self-balance position), and this position was transferred to the cephalostat
      by means of a fluid level device. The differences among sexes were investigated
      by means of Student's t-test, carried out using SPSS (Windows 7.5). RESULTS: It
      was found that there were no sex variations in head position. The linear
      measurements regarding the position of hyoid bone showed statistically
      significant differences with respect to sex. However, hyoid bone position was
      higher and more posterior in females, while natural head position was not
      affected by sex.

PMID- 16427297
TI  - Standards for digital photography in cranio-maxillo-facial surgery - Part I:
      Basic views and guidelines.
AB  - Clinical photography is an essential facility to support the work of cranio
      maxillo-facial surgical departments. This paper highlights the requirements to
      ensure the highest quality and consistency of photographs taken and provides a
      standardized set of both facial and intra-oral views that fit the needs of
      accurate digital photo-documentation in cranio-maxillo-facial surgery.
      Furthermore it gives assistance in the selection of equipment, archival storage
      and error avoidance. These guidelines have been approved in November 2005 by the
      Council of the European Association for Cranio-Maxillo-Facial Surgery and are to
      be understood as a proposal to all our colleagues in Maxillofacial Surgery.

PMID- 16427296
TI  - Maximized combined modality treatment of an unselected population of oral and
      oropharyngeal cancer patients. Final results of a pilot study compared with a
      treatment-dependent prognosis index.
AB  - BACKGROUND: In an attempt to raise the survival of an unselected and
      representative population of oral and oropharyngeal squamous cell cancer
      patients, a pilot study of an integrated four-modality treatment was conceived.
      Final endpoints were compliance, loco-regional control, survival (after complete
      5-year follow-up), and a concept of trial assessment using the treatment
      dependent prognostic index TPI. PATIENTS: Eighty-seven consecutive patients with
      histologically proven untreated stages I-IV disease presented in the period
      between 1997 and 1999 of whom 14 had to be considered uncurable and 73 were fit
      to be treated with the intention of achieving a cure. METHODS: All patients
      received one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2)
      cisplatin (systemically neutralized with sodium thiosulphate), and, if possible,
      by consecutive treatment applying both surgery of the primary tumour and the neck
      lymphatics, as well as by adjuvant radiation over 5 weeks (51.3 Gy) plus
      concurrent chemotherapy (weekly systemic docetaxel 25 mg/m(2)). RESULTS: Ninety
      per cent of all cases and 96% of the patients treated with curative intention
      received more than one modality due to study design. Patient non-compliance in
      the group treated with curative intention has been 18/73 (=25%), and protocol
      compliance has been 32/73 (=44%). The locoregional control rate for all cases was
      71% (62/87 patients) and for the patients treated with curative intention 83.5%
      (61/73 patients). Thirteen/fourteen non-curable patients died after a mean period
      of 4 months. After a median observation time of 5 years, the final absolute
      survival of the unselected population was 53%, and of the patients treated with
      curative intention 62% (especially, 70% and 50% for patients with operable stages
      III and IV, respectively). CONCLUSION: The multimodality regimen as presented
      proved feasible and showed high objective and relative survival rates in
      comparison with known data from tumour registries of unselected populations.
      Intra-arterial chemotherapy should be considered a valuable addition to
      treatment. The potential of survival benefit from this multimodality regimen in
      comparison with the prognosis index TPI should be investigated in further
      studies.

PMID- 16427298
TI  - Atypical cyst formation following chin augmentation using a nasal
      osteocartilaginous graft.
AB  - The purpose of this paper is to present a case of an intraosseous mucocele that
      was detected 5 years after chin augmentation using a nasal osteocartilaginous
      graft. Although complications of this technique have been described as
      negligible, the surgeon must be aware of possible long-term side effects and
      should remove all nasal mucosa from the graft prior to implantation.

PMID- 16427299
TI  - MCI-186 (edaravone), a free radical scavenger, attenuates ischemia-reperfusion
      injury and activation of phospholipase A(2) in an isolated rat lung model after
      18 h of cold preservation.
AB  - OBJECTIVE: Increased microvascular permeability and extravasation of inflammatory
      cells are key events in ischemia-reperfusion (IR) injury. We hypothesized that
      edaravone, a free radical scavenger, is able to attenuate IR lung injury by
      decreasing oxidative stress and phospholipase A(2) (PLA(2)) activation, which
      otherwise may lead to lung injury through PAF receptor (PAF-R) activation.
      METHODS: We used an isolated rat lung model. Five groups were defined (n=7,
      each): in the sham and vehicle group, lungs were immediately washed after
      thoracotomy or perfused for 2h without an ischemic period, respectively. In the
      ischemic groups, 10mg/kg of MCI-186 (edavorane group), 1mg/kg of PAF-R inhibitor
      (ABT-491 group) or saline (control group) were i.v. administered 20 min before
      harvest. Lungs were flushed with LPD solution, stored at 4 degrees C for 18 h,
      and reperfused for 2h. RESULTS: Compared to vehicle group, IR significantly
      decreased the PO(2) level and increased the wet-to-dry ratio, proteins in
      bronchoalveolar lavage (BAL), and myeloperoxidase (MPO) activity in the control
      group, while edaravone treatment maintained the PO(2) similar to the vehicle
      group and significantly reduced edema formation and neutrophil extravasation.
      Consistently, IR significantly increased lipid peroxidation, cytosolic-PLA(2)
      activity mainly via alveolar macrophages, soluble-PLA(2) activity, leukotriene
      B(4), and PAF-R expression in control lungs, together with a decreased PAF
      acetylhydrolase (PAF-AH) activity. Edaravone significantly reduced all of these,
      but increased PAF-AH activity. Furthermore, pharmacological inhibition of the PAF
      R attenuated IR injury resembling edaravone action. CONCLUSION: Edaravone
      attenuates lung IR injury by suppressing oxidative damage and PLA(2) activation,
      which otherwise partially mediates edema formation and neutrophil extravasation
      through PAF-R activation.

PMID- 16427300
TI  - Outpatient thoracic surgical programme in 300 patients: clinical results and
      economic impact.
AB  - OBJECTIVE: To evaluate clinical aspects, results and the economic impact of the
      outpatient thoracic surgery programme (OTSP) developed in our Department.
      METHODS: Prospective study of 300 patients who entered in the OTSP from April
      2001 to March 2005. The procedures performed were video-mediastinoscopy (MC),
      video-thoracoscopic lung biopsy (LB) and video-thoracoscopic bilateral thoracic
      sympathectomy (TS). All procedures were performed under general anaesthesia and
      patients were discharged in 4-6h. We analyse demographic data, the substitution
      index (SI), the admission rate (AR) and readmission rate (RR) after the
      procedure. We calculate the economic impact of stay expenses on our hospital and
      on other Spanish hospitals. RESULTS: The female/male ratio of the 300 patients
      was 83/217, with a mean age of 58.1 years (range: 15-85 years). There were no
      deaths. Mediastinoscopy was performed as outpatient procedure in 210 patients
      (mean age: 65.6 years) out of 244 total MC (SI=86.1%). Two patients were admitted
      (AR=0.95%) to observe a minimal pneumothorax and because of late night end. There
      were no readmissions after MC (RR=0%). We included 32 ambulatory patients for
      lung biopsy (mean age: 61.5 years) out of 64 total LB (SI=50.0%). One patient was
      admitted because of air leak (AR=3.1%) and there were no readmissions after LB
      (RR=0%). Fifty-eight patients were included in the OTSP for bilateral
      sympathectomy (mean age: 27.1 years) out of 83 total TS (SI=69.9%); there were no
      admissions (AR=0%) and one patient was readmitted after 9 days because of a
      hemothorax (RR=1.7%). Sixty-four patients out of the 91 not included in the OTSP
      were included in an 'afternoon surgical programme' and dismissed the morning
      after surgery, without contraindication for their inclusion in the OTSP. The
      hospital's total stay saving was 12,668 euros (88,226 euros if performed
      elsewhere), 42 euros per patient (294 euros per patient if performed elsewhere).
      CONCLUSION: Video-assisted mediastinoscopy, lung biopsy and bilateral
      sympathectomy can be included safely in outpatient thoracic surgical programmes.
      The impact of the economic benefit of OTSP over the conventional hospitalisation
      depends on the Department's previous policy on hospital stays. Further experience
      is needed to increase the substitution index and expand the OTSP to other
      procedures.

PMID- 16427301
TI  - Apoptosis induction and mitochondria alteration in human HeLa tumour cells by
      photoproducts of Rose Bengal acetate.
AB  - The aim of this work was to investigate the apoptosis induction and mitochondria
      alteration after photodamage exerted by incubation of HeLa cells with Rose Bengal
      acetate-derivative (RBAc) followed by irradiation for a total dose of 1.6 J/cm2.
      This treatment was previously demonstrated to reduce cell viability under mild
      treatment conditions, suggesting the restoration of the photoactive molecule in
      particularly sensitive cell sites. Indeed, Rose Bengal (RB) is a very efficient
      photosensitizer, whose photophysical properties are inactivated by addition of
      the quencher group acetate. The RBAc behaves as a fluorogenic substrate by
      entering easily the cells where the original, photoactive molecule is restored by
      specific esterases. Different intracellular sites of photodamage of RB are
      present. In particular, fluorescence imaging of Rodamine 123 and JC-1 labelled
      cells showed altered morphology and loss of potential membrane of mitochondria.
      MTT and NR assays gave indications of alteration of mitochondrial and lysosomal
      enzyme activities. These damaged sites were likely responsible for triggering
      apoptosis. Significant amount of apoptotic cell death (about 40%) was induced
      after light irradiation followed RBAc incubation as revealed by morphological
      (modification of cell shape and blebs formation), cytochemical (FITC-Annexin-V
      positive cells) and nuclear fragmentation assays.

PMID- 16427302
TI  - Zn(II)-phthalocyanines as phototherapeutic agents for cutaneous diseases.
      Photosensitization of fibroblasts and keratinocytes.
AB  - Two tetrasubstituted (RLP024 and RLP040) and one monosubstituted (MRLP101) Zn
      phthalocyanines were readily accumulated by three skin-derived cell lines (HT
      1080 transformed human fibroblasts, 3T3 mouse embryo fibroblasts and HaCaT human
      keratinocytes) upon 1 h-incubation with 0.5-5 microM phthalocyanine
      concentrations. The affinity was markedly larger for the tetra- as compared with
      the mono-substituted phthalocyanine, even though smaller phthalocyanine amounts
      were generally recovered from keratinocytes. As a consequence, the two tetra
      substituted phthalocyanines exhibited a higher phototoxicity against all the
      three cell lines. Typically, the cell survival decreased by at least 80% after 1
      min irradiation with 600-700 nm light at a fluence-rate of 50 mW/cm2 in the
      presence of 5 microM phthalocyanine. Fluorescence microscopy and caspase-3
      activation studies indicate that cell death of fibroblasts largely occurred by a
      random-necrotic process while the keratinocytes underwent cell death
      predominantly via apoptosis in spite of a very similar pattern of subcellular
      distribution of the phthalocyanines.

PMID- 16427303
TI  - Proteasome inhibitors in lung cancer.
AB  - Proteasome inhibition is a novel therapeutic approach that is being investigated
      in non-small cell and small cell lung cancer (NSCLC and SCLC). Proteasome
      inhibition affects a range of intracellular signals and disrupts the levels of
      numerous proteins, causing apoptosis via multiple pathways. Importantly,
      malignant cells are more sensitive to proteasome inhibition than normal cells. A
      number of proteasome inhibitors have demonstrated activity in preclinical
      studies, both as single agents and in combination with conventional and novel
      antineoplastic agents. However, only bortezomib, a dipeptide boronic acid analog,
      has been investigated in lung cancer clinical trials, in which it has shown
      activity as a single agent and in combination regimens. Numerous preclinical and
      clinical studies are ongoing in both NSCLC and SCLC. Proteasome inhibition could
      potentially play a significant role in the future management of these conditions.

PMID- 16427304
TI  - On the distributions of ion/neutral molecule clusters in electrospray and laser
      spray -- a cluster division model for the electrospray process.
AB  - The clustering of a medium-sized, involatile, neutral molecule, octyl beta-D
      glucopyranoside (OG), with Na(+), Ca(2+), and Yb(3+) (M(z+)) ions in electrospray
      (ESI) was investigated using laser spray (LSI). Extensive distributions of
      [(M(z+))(i) (OG)(a)](n+)-clusters, extending beyond 50 kDa, were observed. The
      distributions were highly stable and reproducible and changed only marginally
      when concentrations of electrolyte or neutral compound were varied by orders of
      magnitude. Compared with ESI, laser spray yielded superior intensities,
      particularly of the larger clusters. The cluster distributions demonstrated a
      range of remarkable features. In particular, the Yb(3+)/OG cluster distribution
      was unusual. For example, no clusters with 35-52 or with 110-116 OG molecules
      were observed. The distribution pattern revealed that the clusters were formed as
      a result of cluster dissociations, such as [(Yb(3+))(3)(OG) ( approximately
      110)W](9+) --> [(Yb(3+))(2)(OG)( approximately 90)W](6+) + [(Yb(3+))(1)(OG) (
      approximately 20)W](3+), where W represents the water content at the time of
      dissociation. Based on this study, a cluster division model for electrospray of
      aqueous solutions of strongly solvated ions is proposed: the Rayleigh droplet
      disintegration process, which is well-established for the initial stages of
      electrospray, maintains its general character as it proceeds through a final
      regime of multiply charged cluster dissociations to the singly and multiply
      charged ions in mass spectrometry. In the dissociation of multiply charged
      clusters, the size of each daughter cluster is roughly proportional to the square
      of the cluster charge. Observed cluster distributions are consistent with a
      mixture of symmetric and asymmetric cluster dissociations.

PMID- 16427306
TI  - The ovine nasal mucosa: an alternative tissue site for mucosal immunization.
AB  - The ovine nasal mucosal environment has histological and ultrastructural features
      that resemble well-known inductive sites of mucosa-associated lymphoid tissue. In
      the present study, the nasal mucosa was assessed as a potential mucosal tissue
      site for delivering vaccines to sheep. Sheep were immunized by either injection
      with the model antigen, Keyhole Limpet Haemocyanin (KLH), and aluminium hydroxide
      gel (alum) or by aerosol spray with KLH with and without cholera toxin (CT).
      Sheep immunized by injection with KLH/alum and aerosol spray with KLH/CT induced
      strong anti-KLH IgG and IgA serum antibody responses as well as specific T cell
      memory. Anti-KLH IgG1 responses were significantly higher following immunization
      by injection and no significant differences in anti-KLH IgG2 responses were
      detected between groups. Sheep immunized with KLH by aerosol spray without CT did
      not produce serum antibody and T cell memory responses. Antibody-secreting cells
      were present in the parotid lymph nodes (draining lymph nodes) of sheep immunized
      with KLH/alum and KLH/CT, but secreted only Ag-specific IgG1, and not IgG2 or
      IgA. These results suggest that aerosolization of soluble antigen formulations
      with CT may provide an alternative method of delivering nasal vaccines to sheep
      and other large animal species, and that further improvements in antigen
      penetration of nasal tissues may dramatically improve the strength of the immune
      response.

PMID- 16427307
TI  - Highly efficient expression and purification system of small-size protein domains
      in Escherichia coli for biochemical characterization.
AB  - It is often essential to focus the study on the small-size domains of large
      proteins in eukaryotic cells in the post-genomic era, but the low expression
      level, insolubility, and instability of the domains have been continuing to
      hinder the massive purification of domain peptides for structural and biological
      investigation. In this work, a highly efficient expression and purification
      system based on a small-size fusion partner GB1 and histidine tag was utilized to
      solve these problems. Two vectors, namely pGBTNH and pGBH, were constructed to
      improve expression and facilitate purification. The linker and thrombin cleavage
      site have been optimized for minimal degradation during purification process.
      This system has been tested for eight domain peptides varying in size, linker,
      hydrophobicity, and predicted secondary structure. The results indicate that this
      system is achievable to produce these domain peptides with high solubility and
      stability for further biochemical characterization. Moreover, the fusion protein
      without the linker and thrombin cleavage site is also suitable for spectroscopic
      studies especially for NMR structural elucidation, if the target peptide is prone
      to precipitation or easily degraded during purification. This system will be
      beneficial to the research field of structure and function of small domain and
      peptide fragment.

PMID- 16427308
TI  - Expression and purification of Pseudomonas aeruginosa SecA N-terminal domain:
      stimulation of ATPase activity of the SecAL43P mutant protein.
AB  - Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium which secretes a
      wide range of hydrolytic enzymes, toxins, and virulence factors into the
      extracellular medium. Although P. aeruginosa possesses numerous specific systems
      for the export of proteins across its double-membrane envelopes, the Sec system
      is still the major and essential mechanism. However, very little is known about
      its molecular basis. We constructed, cloned, and expressed the N-terminal 236
      amino acids of PaSecA domain (PaSecAN236), and SecAL43P mutants of P. aeruginosa
      in Escherichia coli BL21.19 (secA(ts)). Here, we describe the purification of
      PaSecAN236 by using osmotic shock as the first step to efficiently release
      targeted protein from cells, followed by cation-exchange and size exclusion
      columns to obtain homogeneous PaSecAN236. The purified PaSecA N-terminal domain
      was functional in stimulating the ATPase activity of mutant SecAL43P protein of
      P. aeruginosa.

PMID- 16427309
TI  - Molecular cloning and functional characterization of beta-N-acetylglucosaminidase
      genes from Sf9 cells.
AB  - Sf9, a cell line derived from the lepidopteran insect, Spodoptera frugiperda, is
      widely used as a host for recombinant glycoprotein expression and purification by
      baculovirus vectors. Previous studies have shown that this cell line has one or
      more beta-N-acetylglucosaminidase activities that may be involved in the
      degradation and/or processing of N-glycoprotein glycans. However, these enzymes
      and their functions remain poorly characterized. Therefore, the goal of this
      study was to isolate beta-N-acetylglucosaminidase genes from Sf9 cells, over
      express the gene products, and characterize their enzymatic activities. A
      degenerate PCR approach yielded three Sf9 cDNAs, which appeared to encode two
      distinct beta-N-acetylglucosaminidases, according to bioinformatic analyses.
      Baculovirus-mediated expression of these two cDNA products induced membrane
      associated beta-N-acetylglucosaminidase activities in Sf9 cells, which cleaved
      terminal N-acetylglucosamine residues from the alpha-3 and -6 branches of a
      biantennary N-glycan substrate with acidic pH optima and completely hydrolyzed
      chitotriose to its constituent N-acetylglucosamine monomers. GFP-tagged forms of
      both enzymes exhibited punctate cytoplasmic fluorescence, which did not overlap
      with either lysosomal or Golgi-specific dyes. Together, these results indicated
      that the two new Sf9 genes identified in this study encode broad-spectrum beta-N
      acetylglucosaminidases that appear to have unusual intracellular distributions.
      Their relative lack of substrate specificity and acidic pH optima are consistent
      with a functional role for these enzymes in glycoprotein glycan and chitin
      degradation, but not with a role in N-glycoprotein glycan processing.

PMID- 16427310
TI  - Gene synthesis, expression, purification, and characterization of human Jagged-1
      intracellular region.
AB  - Notch signaling plays a key role in cell differentiation and is very well
      conserved from Drosophila to humans. Ligands of Notch receptors are type I,
      membrane spanning proteins composed of a large extracellular region and a 100-150
      residue cytoplasmic tail. We report here, for the first time, the expression,
      purification, and characterization of the intracellular region of a Notch ligand.
      Starting from a set of synthetic oligonucleotides, we assembled a synthetic gene
      optimized for Escherichia coli codon usage and encoding the cytoplasmic region of
      human Jagged-1 (residues 1094-1218). The protein containing a N-terminal His(6)
      tag was over-expressed in E. coli, and purified by affinity and reversed phase
      chromatography. After cleavage of the His(6)-tag by a dipeptidyl aminopeptidase,
      the protein was purified to homogeneity and characterized by spectroscopic
      techniques. Far-UV circular dichroism, fluorescence emission spectra,
      fluorescence anisotropy measurements, and (1)H nuclear magnetic resonance
      spectra, taken together, suggest that the cytoplasmic tail of human Jagged-1
      behaves as an intrinsically unstructured domain in solution. This result was
      confirmed by the high susceptibility of the recombinant protein to proteolytic
      cleavage. The significance of this finding is discussed in relation to the
      recently proposed role of the intracellular region of Notch ligands in bi
      directional signaling.

PMID- 16427311
TI  - Current strategies for the use of affinity tags and tag removal for the
      purification of recombinant proteins.
AB  - Affinity tags are highly efficient tools for protein purification. They allow the
      purification of virtually any protein without any prior knowledge of its
      biochemical properties. The use of affinity tags has therefore become widespread
      in several areas of research e.g., high throughput expression studies aimed at
      finding a biological function to large numbers of yet uncharacterized proteins.
      In some cases, the presence of the affinity tag in the recombinant protein is
      unwanted or may represent a disadvantage for the projected application of the
      protein, like for clinical use. Therefore, an increasing number of approaches are
      available at present that are designed for the removal of the affinity tag from
      the recombinant protein. Most of these methods employ recombinant endoproteases
      that recognize a specific sequence. These process enzymes can subsequently be
      removed from the process by affinity purification, since they also include a tag.
      Here, a survey of the most common affinity tags and the current methods for tag
      removal is presented, with special emphasis on the removal of N-terminal
      histidine tags using TAGZyme, a system based on exopeptidase cleavage. In the
      quest to reduce the significant costs associated with protein purification at
      large scale, relevant aspects involved in the development of downstream processes
      for pharmaceutical protein production that incorporate a tag removal step are
      also discussed. A comparison of the yield of standard vs. affinity purification
      together with an example of tag removal using TAGZyme is also included.

PMID- 16427312
TI  - An extracellular exo-beta-(1,3)-glucanase from Pichia pastoris: purification,
      characterization, molecular cloning, and functional expression.
AB  - An extracellular exo-beta-(1,3)-glucanase (designated EXG1) was purified to
      apparent homogeneity from Pichia pastoris X-33 cultures by ammonium sulfate
      fractionation, ion-exchange chromatography, and gel filtration. The native enzyme
      is unglycosylated and monomeric with a molecular mass of approximately 47kDa. At
      its optimal pH of 6.0, the enzyme shows highest activity among physiological
      substrates toward laminarin (apparent Km, 3.5 mg/ml; Vmax, 192 micromole glucose
      produced/min/mg protein) but also hydrolyzes amygdalin and esculin, and the
      chromogenic substrates p-nitrophenyl-beta-D-glucopyranoside and p-nitrophenyl
      beta-D-xylopyranoside. The P. pastoris EXG1 gene was cloned by a PCR-based
      strategy using genomic DNA as template. This intronless gene predicts an ORF that
      encodes a primary translation product of 414 amino acids. We believe that this
      preproprotein is processed sequentially by signal peptidase and a Kex2-like
      endoprotease to yield a mature protein of 392 amino acids (45,376 Da; pI, 4.46)
      that shares 36-64% amino acid identity with other yeast exo-beta-(1,3)-glucanases
      belonging to Glycoside Hydrolase Family 5. It also possesses the eight invariant
      residues and signature pattern [LIV]-[LIVMFYWGA](2)-[DNEQG]-[LIVMGST]-X-N-E-[PV]
      [RHDNSTLIVFY] shown by all Family 5 members. Overexpression of the cloned EXG1
      gene in Pichia cells, followed by Ni-CAM HC resin chromatography, yielded
      milligram quantities of homogeneous recombinant EXG1 in active form for further
      characterization studies.

PMID- 16427313
TI  - The crystal structure of putative precorrin isomerase CbiC in cobalamin
      biosynthesis.
AB  - The leptospira cbiC encodes the enzyme catalyzing the methyl rearrangement
      reaction of the cobalamin biosynthesis pathway. The protein has been cloned and
      overexpressed as a His-tagged recombinant protein in Escherichia coli. The
      crystal structures have been solved in two crystal forms (P4(2)2(1)2 and P3(1)21)
      diffracting to 3.0 and 2.3A resolution, respectively. The structures are similar
      to the precorrin-8x methyl mutase (CobH), an enzyme of the aerobic pathway to
      vitamin B12.

PMID- 16427314
TI  - Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation
      interpreted by electron cryo-microscopy and X-ray crystallography.
AB  - The bacteriophage HK97 capsid is a molecular machine that exhibits large-scale
      conformational rearrangements of its 420 identical protein subunits during capsid
      maturation. Immature empty capsids, termed Prohead II, assemble in vivo in an
      Escherichia coli expression system. Maturation of these particles may be induced
      in vitro, converting them into Head II capsids that are indistinguishable in
      conformation from the capsid of an infectious phage particle. One method of in
      vitro maturation requires acidification to drive the reaction through two
      expansion intermediates (EI-I, EI-II) to its penultimate particle state (EI-III),
      which has 86% more internal volume than Prohead II. Neutralization of EI-III
      produces the fully mature capsid, Head II. The three expansion intermediates and
      the acid expansion pathway were characterized by cryo-EM analysis and 3D
      reconstruction. We now report that, although large-scale structural changes are
      involved, the electron density maps for these intermediate states are readily
      interpreted in terms of quasi-atomic models based on subunit structures
      determined by prior crystallographic analysis of Head II. Progression through the
      expansion intermediate states primarily represents rigid-body rotations and
      translations of the subunits, accompanied by refolding of two small regions, the
      N-terminal arm and a beta-hairpin called the E-loop. Movies made with these
      pseudo-atomic coordinates and the Head II X-ray coordinates illuminate various
      aspects of the maturation pathway in the course of which the pattern of inter
      subunit interactions is sequentially transformed while the integrity of the
      capsid is maintained.

PMID- 16427315
TI  - The pH-dependent unfolding mechanism of P2 myelin protein: an experimental and
      computational study.
AB  - The P2 protein is a small, extrinsic protein of the myelin membrane in the
      peripheral nervous system that structurally belongs to the fatty acid binding
      proteins (FABPs) family, sharing with them a 10 strands beta-barrel structure.
      FABPs appear to be involved in cellular fatty acid transport, but very little is
      known about the role of P2 in the metabolism of peripheral myelin lipids. Study
      of protein conformation at different pHs is a useful tool for the
      characterization of the unfolding mechanisms and the intrinsic conformational
      properties of the protein, and may give insight into factors that guide protein
      folding pathways. In particular, low pH conditions have been shown to induce
      partially folded states in several proteins. In this paper, the acidic unfolding
      of purified P2 protein was studied with both spectroscopic techniques and
      molecular dynamics simulation. Both experimental and computational results
      indicate the presence of a partly folded state at low pH, which shows structural
      changes mainly involving the lid that is formed by the helix-turn-helix domain.
      The opening of the lid, together with a barrel relaxation, could regulate the
      ligand exchanges near the cell membrane, supporting the hypothesis that the P2
      protein may transport fatty acids between Schwann cells and peripheral myelin.

PMID- 16427316
TI  - Prediction of MEF2A-DNA interface by rigid body docking: a tool for fast
      estimation of protein mutational effects on DNA binding.
AB  - The protein-protein docking algorithm ZDOCK has been challenged for the first
      time to predict protein-DNA contacts. The computational approach defined in this
      study has proven effectiveness in fast in silico estimations of mutational
      effects of the MEF2A transcription factor on DNA binding.

PMID- 16427317
TI  - Reliability of techniques to assess human neuromuscular function in vivo.
AB  - The purpose of this study was to comprehensively evaluate the reliability of a
      large number of commonly utilized experimental tests of in vivo human
      neuromuscular function separated by 4-weeks. Numerous electrophysiological
      parameters (i.e., voluntary and evoked electromyogram [EMG] signals), contractile
      properties (i.e., evoked forces and rates of force development and relaxation),
      muscle morphology (i.e., MRI-derived cross-sectional area [CSA]) and performance
      tasks (i.e., steadiness and time to task failure) were assessed from the
      plantarflexor muscle group in 17 subjects before and following 4-weeks where they
      maintained their normal lifestyle. The reliability of the measured variables had
      wide-ranging levels of consistency, with coefficient of variations (CV) ranging
      from approximately 2% to 20%, and intraclass correlation coefficients (ICC)
      between 0.53 and 0.99. Overall, we observed moderate to high-levels of
      reliability in the vast majority of the variables we assessed (24 out of the 29
      had ICC>0.70 and CV<15%). The variables demonstrating the highest reliability
      were: CSA (ICC=0.93-0.98), strength (ICC=0.97), an index of nerve conduction
      velocity (ICC=0.95), and H-reflex amplitude (ICC=0.93). Conversely, the variables
      demonstrating the lowest reliability were: the amplitude of voluntary EMG signal
      (ICC=0.53-0.88), and the time to task failure of a sustained submaximal
      contraction (ICC=0.64). Additionally, relatively little systematic bias
      (calculated through the limits of agreement) was observed in these measures over
      the repeat sessions. In conclusion, while the reliability differed between the
      various measures, in general it was rather high even when the testing sessions
      are separated by a relatively long duration of time.

PMID- 16427318
TI  - Absent-mindedness: Lapses of conscious awareness and everyday cognitive failures.
AB  - A brief self-report scale was developed to assess everyday performance failures
      arising directly or primarily from brief failures of sustained attention
      (attention-related cognitive errors-ARCES). The ARCES was found to be associated
      with a more direct measure of propensity to attention lapses (Mindful Attention
      Awareness Scale--MAAS) and to errors on an existing behavioral measure of
      sustained attention (Sustained Attention to Response Task--SART). Although the
      ARCES and MAAS were highly correlated, structural modelling revealed the ARCES
      was more directly related to SART errors and the MAAS to SART RTs, which have
      been hypothesized to directly reflect the lapses of attention that lead to SART
      errors. Thus, the MAAS and SART RTs appear to directly reflect attention lapses,
      whereas the ARCES and SART errors reflect the mistakes these lapses are thought
      to cause. Boredom proneness was also assessed by the BPS, as a separate
      consequence of a propensity to attention lapses. Although the ARCES was
      significantly associated with the BPS, this association was entirely accounted
      for by the MAAS, suggesting that performance errors and boredom are separate
      consequences of lapses in attention. A tendency to even extraordinarily brief
      attention lapses on the order of milliseconds may have far-reaching consequences
      not only for safe and efficient task performance but also for sustaining the
      motivation to persist in and enjoy these tasks.

PMID- 16427319
TI  - 3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS.
AB  - OBJECTIVE: 40 million people worldwide are now infected with HIV/AIDS, an illness
      that often leads to rapidly progressing dementia and death. Even so, little is
      known about how AIDS affects the brain. Using computational anatomy techniques,
      we mapped how AIDS impacts the corpus callosum (CC) and ventricular system, two
      systems that show prominent changes on MRI. We (1) identified regions with
      greatest differences between AIDS patients and healthy controls and (2)
      correlated specific 3D patterns of structural differences with measures of immune
      system deterioration and cognitive decline. METHODS: 51 3D brain MRI scans from
      30 non-demented AIDS patients (age: 43.4 years +/- 7.6 SD) and 21 HIV
      seronegative controls (age: 39.5 years +/- 12.2) were aligned to ICBM standard
      space. 3D surface mesh reconstructions of the lateral ventricles and CC were
      spatially averaged and compared across diagnostic groups. Structural alterations
      were correlated with viral load, T cell counts, and cognitive impairment.
      RESULTS: Statistical maps revealed the 3D profile of ventricular expansion and
      callosal thinning in AIDS. Specific 3D ventricular changes were linked with
      immune system decline (CD4+ T cell counts; P < 0.001) and cognitive impairment (P
      < 0.009), but not viral load. Frontal horn maps distinguished AIDS patients from
      controls better than occipital and temporal horn measures. T cell decline linked
      with callosal thinning in anterior regions connecting frontal areas with greatest
      cortical atrophy. CONCLUSION: These maps (1) reveal how brain changes in HIV/AIDS
      relate to immune decline and impaired cognition, and, after further validation
      and testing, (2) may offer possible neuroimaging markers for anti-viral drug
      trials, which gauge how well treatments oppose disease progression in the brain.

PMID- 16427320
TI  - Improvement-related functional plasticity following pitch memory training.
AB  - Functional activation patterns of an auditory working memory task were examined
      prior to and after 5 days of training (1 h/day). A control group with no training
      was scanned twice at the same intervals to assess test-retest effects. Based on
      behavioral improvement scores, the training group (n = 14) was divided into
      "Strong-Learners (SL)" and "Weak-Learners (WL)". No significant functional or
      structural brain differences were seen between the SL and WL groups prior to
      training. Imaging contrasts comparing post- with pre-training sessions showed a
      significant signal increase in the left Heschl's gyrus (HG) as well as in the
      left posterior superior temporal and supramarginal gyrus for the SL group, while
      the WL group showed significant signal increases in the left HG and anterior
      insular cortex as well as in a lingual-orbitofrontal-parahippocampal network. The
      test-retest analysis in the control group revealed only minimal signal increases
      in a right dorsolateral prefrontal region. A random effects analysis comparing
      the SL group with the WL group using the post- and pre-training contrast images
      showed increased activation only in the left supramarginal gyrus but not in HG.
      The importance of HG in pitch discrimination has been established in previous
      studies. The pitch memory component differentiated our task from a straight pitch
      discrimination task. It is most likely that the activation of the SMG reflects
      its importance in the short-term storage of auditory material, and it was this
      activation that best differentiated between subjects' levels of performance.

PMID- 16427321
TI  - Functional imaging of working memory following normal sleep and after 24 and 35 h
      of sleep deprivation: Correlations of fronto-parietal activation with
      performance.
AB  - Working memory was evaluated after normal sleep, and at 24 and 35 h of sleep
      deprivation (SD) in 26 healthy young adults to examine the neural correlates of
      inter-individual differences in performance. The extent of performance decline
      was not significantly different between the two SD test periods although there
      was greater variability in performance at SD35. In both SD sessions, there was
      reduced task-related activation (relative to normal sleep) in both superior
      parietal regions and the left thalamus. Activation of the left parietal and left
      frontal regions after normal sleep was negatively correlated with performance
      accuracy decline from normal sleep to SD24 thus differentiating persons who
      maintained working memory performance following SD from those who were vulnerable
      to its effects.

PMID- 16427322
TI  - Characterization of displaced white matter by brain tumors using combined DTI and
      fMRI.
AB  - In vivo white matter tractography by diffusion tensor imaging (DTI) has become a
      popular tool for investigation of white matter architecture in the normal brain.
      Despite some unresolved issues regarding the accuracy of DTI, recent studies
      applied DTI for delineating white matter organization in the vicinity of brain
      lesions and especially brain tumors. Apart from the intrinsic limitations of DTI,
      the tracking of fibers in the vicinity or within lesions is further complicated
      due to changes in diseased tissue such as elevated water content (edema), tissue
      compression and degeneration. These changes deform the architecture of the white
      matter and in some cases prevent definite selection of the seed region of
      interest (ROI) from which fiber tracking begins. We show here that for displaced
      fiber systems, the use of anatomical approach for seed ROI selection yields
      insufficient results. Alternatively, we propose to select the seed points based
      on functional MRI activations which constrain the subjective seed ROI selection.
      The results are demonstrated on two major fiber systems: the pyramidal tract and
      the superior longitudinal fasciculus that connect critical motor and language
      areas, respectively. The fMRI based seed ROI selection approach enabled a more
      comprehensive mapping of these fiber systems. Furthermore, this procedure enabled
      the characterization of displaced white matter using the eigenvalue decomposition
      of DTI. We show that along the compressed fiber system, the diffusivity parallel
      to the fiber increases, while that perpendicular to the fibers decreases, leading
      to an overall increase in the fractional anisotropy index reflecting the
      compression of the fiber bundle. We conclude that definition of the functional
      network of a subject with deformed white matter should be done carefully. With
      fMRI, one can more accurately define the seed ROI for DTI based tractography and
      to provide a more comprehensive, functionally related, white matter mapping, a
      very important tool used in pre-surgical mapping.

PMID- 16427323
TI  - Native and non-native reading of sentences: an fMRI experiment.
AB  - The processing of syntactic and semantic information in written sentences by
      native (L1) and non-native (L2) speakers was investigated in an fMRI experiment.
      This was done by means of a violation paradigm, in which participants read
      sentences containing either a syntactic, a semantic, or no violation. The results
      of this study were compared to those of a previous fMRI study, in which auditory
      sentence processing in L1 and L2 was investigated. The results indicate greater
      activation for L2 speakers as compared to L1 speakers when reading sentences in
      several language- and motor-related brain regions. The processing of
      syntactically incorrect sentences elicited no reliably greater activation in
      language areas in L2 speakers. In L1 speakers, on the other hand, syntactic
      processing, as compared to semantic processing, was associated with increased
      activation in left mid to posterior superior temporal gyrus. In response to the
      processing of semantically incorrect sentences, both L2 and L1 speakers
      demonstrated increased involvement of left inferior frontal gyrus. The results of
      this study were compared to a previously conducted fMRI study, which made use of
      identical sentence stimuli in the auditory modality. Results from the two studies
      are in general agreement with one another, although some differences in the
      response of brain areas very proximal to primary perceptual processing areas
      (i.e. primary auditory and visual cortex) were observed in conjunction with
      presentation in the different modalities. The combined results provide evidence
      that L1 and L2 speakers rely on the same cortical network to process language,
      although with a higher level of activation in some regions for L2 processing.

PMID- 16427325
TI  - Molecular systematics of Vampyressine bats (Phyllostomidae: Stenodermatinae) with
      comparison of direct and indirect surveys of mitochondrial DNA variation.
AB  - Approximately 29 species in seven genera (Chiroderma, Mesophylla, Platyrrhinus,
      Uroderma, Vampyressa, Vampyriscus, and Vampyrodes) compose the Subtribe
      Vampyressina, a group of New World leaf-nosed bats (Phyllostomidae) specialized
      in fruit-eating. A recent study of restriction-site variability within the
      mitochondrial ND3-ND4 gene region contrasts with other molecular data, including
      sequence data from other mitochondrial genes, by suggesting that the monotypic
      genus Ectophylla (E. alba) also is member of the group and is related closely to
      Mesophylla. In this study, we address possible explanations for why the
      restriction-site data appear to contradict other molecular data by performing
      phylogenetic analysis of DNA sequence variation (direct survey) in the ND3-ND4
      region and cytochrome b gene and by re-assessing ND3-ND4 restriction-site
      variability in the known sequences (indirect survey). Results from analysis of
      sequence data reject the Ectophylla-Mesophylla hypothesis (P<0.001) and suggest
      four primary lineages within Vampyressina: (1) Mesophylla-Vampyressa; (2)
      Chiroderma-Vampyriscus; (3) Platyrrhinus-Vampyrodes; and (4) Uroderma. We also
      find no support for the Ectophylla-Mesophylla hypothesis in our re-analysis of
      ND3-ND4 restriction-site variability, and suggest the differences between
      molecular studies have a methodological basis.

PMID- 16427324
TI  - Continuous ASL perfusion fMRI investigation of higher cognition: quantification
      of tonic CBF changes during sustained attention and working memory tasks.
AB  - Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical
      neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability
      to quantify the absolute level of cerebral blood flow (CBF) make the method ideal
      for longitudinal designs or low frequency paradigms. Despite the usefulness in
      the study of cognitive dysfunctions in clinical populations, perfusion activation
      studies to date have been conducted for simple sensorimotor paradigms or with
      single-slice acquisition, mainly due to technical challenges. Using our recently
      developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we
      assessed the feasibility of a higher level cognitive activation study in twelve
      healthy subjects. Taking advantage of the ASL noise properties, we were able to
      study tonic CBF changes during uninterrupted 6-min continuous performance of
      working memory and sustained attention tasks. For the visual sustained attention
      task, regional CBF increases (6-12 ml/100 g/min) were detected in the right
      middle frontal gyrus, the bilateral occipital gyri, and the anterior
      cingulate/medial frontal gyri. During the 2-back working memory task,
      significantly increased activations (7-11 ml/100 g/min) were found in the left
      inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior
      cingulate/medial frontal gyri, and the left occipital gyrus. Locations of
      activated and deactivated areas largely concur with previous PET and BOLD fMRI
      studies utilizing similar paradigms. These results demonstrate that CASL
      perfusion fMRI can be successfully utilized for the investigation of the tonic
      CBF changes associated with high level cognitive operations. Increased
      applications of the method to the investigation of cognitively impaired
      populations are expected to follow.

PMID- 16427326
TI  - Sagittal plane movement at the tibiofemoral joint influences patellofemoral joint
      structure in healthy adult women.
AB  - OBJECTIVES: The influence exerted on cartilage and bone volumes by locomotor
      patterns is poorly understood, particularly at the patellofemoral joint. The aim
      of this study was to investigate the relationship between sagittal plane movement
      at the tibiofemoral joint and patella cartilage and bone volumes during the
      locomotion of healthy adult females. METHODS: Three-dimensional Vicon gait
      analyses and magnetic resonance imaging were performed on 20 healthy adult women.
      The relationships between the degree of tibiofemoral flexion and extension at
      varying stages of the gait cycle and the concomitant medial, lateral and total
      patella cartilage and total bone volumes were examined. RESULTS: For every degree
      the knee flexed during mid-stance, there was a 62.8 microL (95% confidence
      interval 3.7-122.0) increase in the medial patella facet cartilage volume after
      adjustment for age and the body mass index (BMI) (P = 0.04). A similar
      relationship that approached significance was observed for the lateral patella
      facet cartilage volume after adjustment for age and the BMI (P = 0.08). No
      association was observed between the sagittal plane tibiofemoral movements and
      the patella bone volume. CONCLUSIONS: The association between patella cartilage
      volume and tibiofemoral knee movement suggests that for every degree increase in
      knee flexion during mid-stance, there is an associated increase in patella
      cartilage volume. This may be the result of the geometry of the femoral condyle
      influencing patella tracking and or the retropatellar load exerted on the patella
      during walking. These results may have important implications for people who
      hyperextend their knee during gait and the pathogenesis of patellofemoral
      osteoarthritis.

PMID- 16427327
TI  - Characterization of pro-apoptotic and matrix-degradative gene expression
      following induction of osteoarthritis in mature and aged rabbits.
AB  - OBJECTIVE: The genetic and molecular changes leading to the distinctive
      alterations of aged cartilage and its propensity for developing osteoarthritis
      (OA) are unknown. We hypothesized that pro-apoptotic and matrix-degradative gene
      expression in a rabbit model of induced OA using mature and aged animals might
      elucidate this relationship. METHODS: Groups of six mature and aged rabbits
      underwent anterior cruciate ligament transection (ACLT) and were sacrificed 4
      weeks after surgery to create an Outerbridge grade II OA. RNA was extracted from
      the articular cartilage and menisci of the affected knee and was examined with
      regard to expression of the following genes: Caspase 8, Fas, Fas ligand (Fas-L),
      p53, aggrecanase, matrix metalloproteinase (MMP)-1, and MMP-3-MMP-13. A second
      cohort of mature and aged animals was sacrificed with no intervention to the
      joint and gene expression was assessed in a similar manner. RESULTS: Fas and
      Caspase 8 showed significantly increased expression in the cartilage of mature
      animals with induced OA when compared to unoperated controls while induction of
      OA in aged rabbits did not significantly increase expression of any of the
      apoptosis genes. Among unoperated animals, the aged cohort showed significantly
      increased expression of MMP-1 and aggrecanase in cartilage when compared to
      mature animals. MMP-13 expression was upregulated in aged cartilage following
      induction of OA. Although ACLT animals showed gross thinning and irregularities
      within the meniscus, only the expression of Caspase 8 in the aged rabbits was
      significantly increased after induction of OA. CONCLUSIONS: Aging of articular
      cartilage shares some qualities with the development of OA, as seen in the
      parallel increases in gene expression of Caspase 8 and Fas. Although this may
      imply a common mechanism of cartilage degeneration in aging and OA or even a
      spectrum of disease, both are complex processes requiring further study.

PMID- 16427328
TI  - Peroxynitrite-modified collagen-II induces p38/ERK and NF-kappaB-dependent
      synthesis of prostaglandin E2 and nitric oxide in chondrogenically differentiated
      mesenchymal progenitor cells.
AB  - OBJECTIVE: Peroxynitrite (ONOO(-)) is formed in the inflamed and degenerating
      human joint. Peroxynitrite-modified collagen-II (PMC-II) was recently discovered
      in the serum of patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
      Therefore we investigated the cellular effects of PMC-II on human mesenchymal
      progenitor cells (MPCs) as a model of cartilage and cartilage repair cells in the
      inflamed and degenerating joint. DESIGN: MPCs were isolated from the trabecular
      bone of patients undergoing reconstructive surgery and were differentiated into a
      chondrogenic lineage. Cells were exposed to PMC-II and levels of the
      proinflammatory mediators nitric oxide (*NO) and prostaglandin E(2) (PGE(2))
      measured. Levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2), phosphorylated mitogen activated protein kinases (MAPKs) and nuclear
      factor kappa B (NF-kappaB) activation were measured by enzyme linked
      immunosorbent assay (ELISA) together with specific MAPK and NF-kappaB inhibitors.
      RESULTS: PMC-II induced ()NO and PGE(2) synthesis through upregulation of iNOS
      and COX-2 proteins. PMC-II also lead to the phosphorylation of MAPKs,
      extracellularly regulated kinase 1/2 (ERK1/2) and p38 [but not c-Jun NH(2)
      terminal kinase (JNK1/2)] and the activation of proinflammatory transcription
      factor NF-kappaB. Inhibitors of p38, ERK1/2 and NF-kappaB prevented PMC-II
      induced ()NO and PGE(2) synthesis, iNOS and COX-2 protein expression and NF
      kappaB activation. CONCLUSION: iNOS, COX-2, NF-kappaB and MAPK are known to be
      activated in the joints of patients with OA and RA. PMC-II induced iNOS and COX-2
      synthesis through p38, ERK1/2 and NF-kappaB dependent pathways suggesting a
      previously unidentified pathway for the synthesis of the proinflammatory
      mediators, ()NO and PGE(2), further suggesting that inhibitors of these pathways
      may be therapeutic in the inflamed and degenerating human joint.

PMID- 16427329
TI  - Evidence of a role for multiple memory systems in behavioral extinction.
AB  - The acquisition of learned behavior involves multiple memory systems, and
      hippocampal system damage impairs cognitive learning while leaving stimulus
      response habit learning intact. In view of evidence that extinction also involves
      new learning, the present experiments examined whether multiple memory systems
      theory may be applicable to the neural bases of extinction. Adult Long-Evans rats
      were trained to run in a straight-alley maze for food reward. Twenty-four hours
      later, rats matched for runway latencies during acquisition received extinction
      training. In a response extinction condition conducive to habit learning, rats
      performed a runway approach response to an empty food cup. In a latent extinction
      condition conducive to cognitive learning, rats were placed at an empty food cup
      without performing a runway approach response. Prior to daily extinction
      training, neural activity of the dorsal hippocampus was reversibly inactivated
      via infusion of bupivacaine (0.75%, 0.5 microl/side). Control rats receiving
      saline infusions displayed extinction behavior in both the response and latent
      training conditions. In contrast, rats receiving bupivacaine extinguished
      normally in the response condition, but did not display latent extinction. The
      findings (1) confirm that learning underlying extinction of the same overt
      behavior can occur with or without explicit performance of the previously
      acquired response, (2) indicate that extinction learning produced by response and
      latent training procedures can be neuroanatomically dissociated, and (3) suggest
      that similarly to initial task acquisition, the hippocampus may critically
      mediate extinction in situations requiring the use of cognitive learning, such as
      when performance of a previously acquired response habit is prevented.

PMID- 16427330
TI  - Endovascular repair for aorto-enteric fistula: a bridge too far or a bridge to
      surgery?
AB  - PURPOSE: To review our experience of endovascular treatment of aorto-enteric
      fistula (AEF). METHODS: Between March 1999 and March 2005, 15 patients in five
      university and teaching hospitals in Belgium and The Netherlands were treated for
      AEF by endovascular repair. Twelve (80%) were male. The mean age was 67 years.
      Thirteen (87%) had had previous aortic or iliac surgery, 1.7-307 months before.
      All patients showed clinical or biochemical signs of bleeding. Eight (53%) were
      in shock, five (33%) had systemic signs of infection. Eight (53%) patients were
      treated in an emergency setting. Ten (67%) were treated with an aortouniiliac
      device, three (20%) with an aortobiiliac device, one with a tube graft and one
      with occluders only. All patients received antibiotics postoperatively for a
      prolonged period of time. RESULTS: All AEF were successfully sealed, the 30-days
      mortality was nil. Mean hospital stay was 20 (2-81) days. One patient died 2.7
      months later of postoperative complications, one died of lung cancer. Until now,
      there are no signs of reinfection in four (27%) patients (mean follow-up 15.7 (1
      44) months). However, reinfection or recurrent AEF occurred in nine (60%)
      patients after 9.5 (0.61-31) months. Seven patients were reoperated successfully,
      two patients died after reintervention. CONCLUSION: Endovascular sealing of AEF
      is a promising technique, which provides time to treat shock, local and systemic
      infection, and co-morbidity. This creates a better situation to perform open
      repair in the future with possibly better outcome. Danger of reinfection remains
      high. Endovascular sealing of AEF should, therefore, be seen as a bridge to open
      surgery when possible.

PMID- 16427331
TI  - A new strategy for treatment of a congenital arteriovenous fistula of the neck.
      Case report.
AB  - Congenital arteriovenous fistulas (AVF) without associated vascular malformations
      are uncommon. Only a very few cases of AVF have been reported in the neck. We
      describe our findings in a patient with AVF treated by a combined vascular and
      endovascular approach.

PMID- 16427332
TI  - Axillo-iliac conduit for haemodialysis vascular access.
AB  - OBJECTIVES: To describe a series of venous surgical procedures performed to
      maintain vascular access. METHODS: We report eight patients with end-stage renal
      failure (ESRF) who had complex renal access problems. Three patients had central
      venous occlusion and underwent veno-venous axillo-iliac bypass. In five further
      patients with a symptomatic central venous obstruction we performed axillo-iliac
      arterio-venous grafting (AVGs) in order to achieve haemodialysis access. All
      patients were assessed pre-operatively with duplex ultrasound and venogram of
      upper and lower limbs. The axillary artery or vein, and iliac vein were
      approached via infraclavicular and extra-peritoneal groin incisions,
      respectively. Non-externally-supported polytetrafluoroethylene (PTFE) was used as
      a conduit in all patients and anti-coagulation regimen were commenced post
      operatively. RESULTS: Following venous diversion surgery, there was a dramatic
      improvement in the facial and limb swelling experienced by the patients. There
      was no significant peri-operative morbidity. The veno-venous graft is still
      patent at 14 months in patient one, at 10 months in patient two, and 5 months in
      patient three. In the second group, who had arterio-venous grafts, the mean
      follow-up was 13.2 (7-20) months with a secondary patency rate of 80% at 6
      months. Four patients had patent, usable grafts at 12 months. In two cases, graft
      occlusion was treated with successful thrombectomy. CONCLUSION: Axillary-iliac
      veno-venous diversion can overcome the symptoms and complications of superior
      vena cava and innominate vein obstruction. Although, axillo-iliac arterio-venous
      graft fistulae formation was previously described it has not been widely used. We
      have found the procedure to have low morbidity and advocate its use in these
      complex cases.

PMID- 16427333
TI  - Letter to editor--EJVES3149 and EVES2690R.

PMID- 16427334
TI  - Carotid plaque texture analysis can predict the incidence of silent brain
      infarcts among patients undergoing carotid endarterectomy.
AB  - OBJECTIVE: To evaluate the correlation between microembolism (ME) and incidence
      of silent brain infarcts during carotid endarterectomy. MATERIALS AND METHODS:
      Patients were assessed using transcranial Doppler, carotid ultrasound and pre-
      and postoperative magnetic resonance imaging (MRIs). The clinical status, need
      for shunt insertion and significant decrease in the blood flow in the middle
      cerebral artery were recorded. All data were analysed using multivariate
      regression models. RESULTS: Out of the 76 patients examined, 17 (22%) had new
      postoperative lesions seen on MRI. Three of them (4%) were symptomatic, 14 (18%)
      were asymptomatic. The multivariate regression models showed that ME is a potent
      predictor of "silent" ischemic brain lesions, at p<0.001 (OR [95% CI]-1.1 [1.05,
      1.2]). Digital plaque texture analysis predicted ME (p=0.028; OR [95% CI]-0.32
      [0.12, 0.89]). The risk of ME increases steadily with the decrease in the
      echogenicity of the plaque. CONCLUSIONS: ME is a potent predictor of "silent"
      ischemic brain lesions among patients with carotid stenosis. An analysis of
      plaque texture can predict the degree of ME during endarterectomy and is more
      precise than the standard GSM.

PMID- 16427335
TI  - Ultrasound based measurement of 'carotid stenosis >70%': an audit of UK practice.
AB  - OBJECTIVES: To determine velocity thresholds for diagnosing 'carotid stenosis
      >70%' and whether Vascular Studies Units in the United Kingdom used ECST or
      NASCET measurement methods. DESIGN: Questionnaire to 102 members of the Society
      of Vascular Technology of Great Britain and Ireland. RESULTS: One quarter (26%)
      of respondents reported that their unit used the NASCET measurement method, 31%
      used the ECST method, while 43% did not know. When all velocity criteria were
      pooled and compared, an almost equal proportion of ECST, NASCET and 'do not know'
      respondents used a peak systolic velocity threshold of >230 cm/s as being
      diagnostic of a 'stenosis >70%'. Interestingly, this velocity is now the
      threshold proposed by a North American consensus group for diagnosing a NASCET
      stenosis of >70%. CONCLUSIONS: This audit suggests that there is considerable
      confusion about what constitutes an ultrasound based diagnosis of 'stenosis >70%
      in the United Kingdom.

PMID- 16427336
TI  - Trained legs for cardiovascular fitness in peripheral arteriopathy.

PMID- 16427337
TI  - Use of a pneumatic tourniquet improves outcome following trans-tibial amputation.
AB  - BACKGROUND: It is traditionally taught that a pneumatic tourniquet is
      contraindicated for trans-tibial amputations in patients with peripheral arterial
      disease. However, tourniquets are used successfully during total knee
      arthroplasty in elderly patients. Vascular patients undergoing a trans-tibial
      amputation have a high perioperative mortality and morbidity-notably the need for
      wound revision or a higher amputation level. We hypothesised that a tourniquet,
      used during amputation, would reduce blood loss and subsequent complications
      without compromising healing. METHODS: This was a prospective non-randomized
      study of 89 adult patients who underwent a trans-tibial amputation between
      January 2001 and December 2003. The endpoints were: haemoglobin levels, the need
      for blood transfusion, perioperative morbidity, revision rate and mortality.
      Patients were divided into two groups: a group with a pneumatic tourniquet (n=42)
      and a group without (n=47). RESULTS: The haemoglobin fall was 14.8% in the non
      tourniquet group and 5.6% in the tourniquet group, with a higher need for
      transfusion in the non-tourniquet group. The revision rate was 14.3% in the
      tourniquet group and significantly higher in the non-tourniquet group (38.3%).
      Mortality was similar in both groups: 7.1% for the tourniquet and 6.4% for the
      non-tourniquet group. CONCLUSION: The use of a pneumatic tourniquet is safe and
      significantly reduces both blood loss and transfusion requirements during trans
      tibial amputation. A pneumatic tourniquet reduces revision rates by over 50%,
      with subsequent cost savings.

PMID- 16427339
TI  - Thrombolysis for acute lower limb ischaemia--a prospective, randomised,
      multicentre study comparing two strategies.
AB  - OBJECTIVES: To test if initial high-dose, pulse-spray thrombolysis improves the
      early and late outcome of lower limb ischaemia as compared with low-dose infusion
      alone. DESIGN: Prospective randomised multicentre study. MATERIAL AND METHODS:
      Patients with acute and sub-acute (<30 days) lower limb ischaemia were randomised
      following angiography. Group 1 (n=58) received pulse-spray infusion of
      recombinant plasminogen activator (rt-PA, 15 mg/h) for 2h followed by low-dose
      infusion if needed. Group 2 (n=63) were only treated with low-dose infusion
      (0.5mg/h) of rt-PA for 48 h. Underlying lesions were corrected if required.
      RESULTS: The study was stopped prematurely. Complications were equally frequent
      in both groups. More than 75% lysis was accomplished in 78 versus 67% of the
      patients (p=0.21). Primary endpoints (re-occlusion, incomplete lysis, life
      threatening complication, amputation, or death) were reached in 24 versus 32% of
      the patients (p=0.35). Neither vascular patency nor clinical parameters differed
      during the first year, but re-interventions tended to be more frequent (p=0.040
      at 1 month; p=0.090 at 1 year) and of a greater magnitude (p=0.028) in group 2.
      CONCLUSIONS: There was no obvious advantage with initial high-dose thrombolysis,
      which may be a type-2 error. A reduction of major re-interventions was recorded.

PMID- 16427340
TI  - Inflammation and Chlamydia pneumoniae infection correlate with the severity of
      peripheral arterial disease.
AB  - BACKGROUND: Our aim was to investigate the association of inflammation and
      Chlamydia pneumoniae infection with the presence and severity of peripheral
      arterial disease. METHODS: Twenty-eight patients whose initial claudication
      distance (ICD) in the traditional constant-load treadmill test was <200 m,
      underwent femoral endarterectomy as part of their interventional treatment (group
      A). Group B consisted of 23 patients whose ICD was >200 m and were put on
      medication and a daily exercise program. The control group consisted of 30 non
      vascular patients of the Ophthalmology Department (group C). We measured the
      levels of C-reactive protein, fibrinogen, vascular cell adhesion molecule-1 and
      tumor necrosis factor-alpha, and the titers of IgA and IgG antibodies against C.
      pneumoniae in the serum of all the patients. Finally, the atheromas and vein
      segments of group A patients, were immunohistochemically (IHC) examined for the
      presence of C. pneumoniae. RESULTS: Peripheral arterial disease (PAD) patients,
      had significantly higher CRP (p=0.026) and anti-Cp IgA levels (p=0.001) when
      compared to control subjects, after a multiple linear regression analysis. The
      odds ratio for the prevalence of femoral atherosclerosis was 3.16 for IgA
      seropositive patients (CI 1.15-8.67). When comparing group A and group B
      patients, CRP (p=0.003) and IgA (p=0.011), were significantly correlated with
      severe PAD. Group A patients with positive immunohistochemical examination of the
      plaque, had higher anti-Cp IgA levels (p=0.023) and TNF-alpha values (p=0.031),
      compared to the IHC negative patients. C. pneumoniae was detected in 50% of the
      femoral atheromas, but in only 3.6% of the veins. CONCLUSION: This study supports
      the hypothesis that inflammation (CRP) and chronic C. pneumoniae infection (IgA
      seropositivity), have an important role in lower limb atherosclerosis and
      correlate with the severity of the disease.

PMID- 16427341
TI  - Editorial.

PMID- 16427342
TI  - Homology modeling of human sialidase enzymes NEU1, NEU3 and NEU4 based on the
      crystal structure of NEU2: hints for the design of selective NEU3 inhibitors.
AB  - Four types of human sialidases have been cloned and characterized at the
      molecular level. They are classified according to their major intracellular
      location as intralysomal (NEU1), cytosolic (NEU2), plasma membrane (NEU3) and
      lysosomal or mitochondrial membrane (NEU4) associated sialidases. These human
      isoforms are distinct from each other in their enzymatic properties as well as
      their substrate specificity. Altered expression of sialidases has been correlated
      with malignant transformation of cells and different sialidases have been known
      to behave differently during carcinogenesis. Particularly, increased expression
      of NEU3 has been implicated in the survival of various cancer cells and also in
      the development of insulin resistance. In the present study, we have modeled
      three-dimensional structures of NEU1, NEU3 and NEU4 based on the crystal
      structure of NEU2 using the homology modeling program MODELER. The best model in
      each enzyme case was chosen on the basis of various standard protein analysis
      programs. Predicted structures and the experimental protein-ligand complex of
      NEU2 were compared to identify similarities and differences among the active
      sites. The molecular electrostatic potential (MEP) was calculated for the
      predicted models to identify the differences in charge distribution around the
      active site and its vicinity. The primary objective of the present work is to
      identify the structural differences between the different isoforms of human
      sialidases, namely NEU1, NEU2, NEU3 and NEU4, thus providing a better insight
      into the differences in the active sites of these enzymes. This can in turn guide
      us in the better understanding and rationale of the differential substrate
      recognition and activity, thereby aiding in the structure-based design of
      selective NEU3 inhibitors.

PMID- 16427343
TI  - A reactivity index study to monitor the role of solvation on the interaction of
      the chromophores with amino-functional silanol surface for colorimetric sensors.
AB  - Amino-functional silanol surface are mostly used for the immobilization of
      inorganic ions, molecules, organic or biochemical molecules onto the mesopore
      surface. In analytical chemistry, the metal ion uptake was visualized through
      colorimetric sensors using chromophore molecules. One needs to know the structure
      property correlation between the chromophore and silylating agent while choosing
      chromophore, which is very important to design the sensors. We have used two
      chromophores representative of hydrophobic and hydrophilic type. We used density
      functional calculation on all the interacting molecules in both the unsolvated
      phase and solvated medium within the domain of hard soft acid base principle
      (HSAB) to look at the localized activity of the interacting atoms of these
      reacting molecules to formulate a priori rule to choose of the best chromophore.
      We have as well postulated the mechanism of interaction between chromophore and
      the silylating agent. The results were compared with experiment and it is
      observed that solvation plays a detrimental role in the binding of chromophore
      with silylating agent. The results also show that, the range of reactivity index
      can be used as a suitable property to scale activity of chromophore molecules
      suitable for the sensing process. It is observed that the hydrophobic chromophore
      binds stronger with both the metal and the silylating agent; whereas for the
      hydrophilic one, it binds only with the silylating agent when solvated and in all
      cases the metal ion binding is weaker compared to that of the hydrophobic one.

PMID- 16427344
TI  - Construction of a 3D model of CP12, a protein linker.
AB  - The chloroplast protein CP12 is known to play a leading role in a complex
      formation with the enzymes GAPDH and PRK. As a preliminary step towards the
      understanding of the complex formation mechanism and the exact role of this
      protein linker, a comparative modelling of the CP12 protein of the green alga
      Chlamydomonas reinhardtii was performed. Because of the very few structural
      information and poor template similarities, the derivation of the model consisted
      in an iterative trial-and-error procedure using the comparative modelling program
      MODELLER, the following three structure validation programs PROCHECK, PROSA, and
      WHATIF, and molecular mechanics energy refinement of the model using the program
      CHARMM. The analysis of the final model reveals a scaffold of key residues that
      is believed to be essential in the folding mechanism and that coincides with the
      residues conserved throughout the CP12 family. Our results suggest that this
      protein is a typical disordered protein. Finally, the various mechanisms by which
      the CP12 protein can self-interact or binds to other enzymes are discussed in
      light of its modelled structure and characteristics.

PMID- 16427345
TI  - Changes in free amino acids in Alphitobius diaperinus (Coleoptera: Tenebrionidae)
      during thermal and food stress.
AB  - Temporal changes in free amino acid pools are examined in starved and cold
      exposed (10 degrees C) beetles (Alphitobius diaperinus) (control beetles; 4, 7,
      14, 28 and 56 days of cold-exposure). The range of individual responses and the
      effect of gender on survival and free amino acid levels are evaluated. Females
      survived significantly longer (Lt50 and Lt90) than males under stressing
      conditions. Pro, Gln, Ala, Arg and Thr are the major components of the free amino
      acid pool in the whole body of adult beetles. Multivariate analysis indicates
      that the duration of exposure explains most of the observed variation in amino
      acid levels, while sex effect is not significant. Moreover, amino acid levels
      fluctuate strongly within each sampled date, revealing a high inter-individual
      heterogeneity. However, this heterogeneity decreases after four weeks of cold
      exposure and starvation. The increase in Ala level and the concomitant decrease
      of Pro after four weeks suggest that Pro might be an important fuel for
      metabolism when fat reserves are reduced. We conclude that changes in free amino
      acid pools are due to a combination of reduced individual heterogeneity, cold
      acclimation and amino acid degradation for energetic purposes.

PMID- 16427347
TI  - Role of structural cells of the cornea and conjunctiva in the pathogenesis of
      vernal keratoconjunctivitis.
AB  - Vernal keratoconjunctivitis (VKC) is a severe type of allergic conjunctival
      disease characterized by the presence both of various corneal epithelial and
      stromal lesions as well as of conjunctival proliferative changes such as giant
      papillae of the upper tarsal conjunctiva and limbal lesions. These clinical
      findings as well as various pathophysiological characteristics of VKC are
      distinct from those of other types of ocular allergy and allergic diseases of
      other organs. The outer eye possesses specific allergological characteristics,
      one of which is communication between the cornea and conjunctiva through a thin
      layer of tear fluid. Fibroblasts of the cornea and the conjunctiva are activated
      by proinflammatory and T helper 2 (Th2) cell-derived cytokines. Corneal
      fibroblasts enhance ocular allergic reactions as a result of their activation
      induced expression both of chemokines such as eotaxin and TARC as well as of
      adhesion molecules such as ICAM-1 and VCAM-1, all of which together promote the
      activation and infiltration of eosinophils and Th2 lymphocytes. In contrast,
      corneal epithelial cells suppress such reactions by physically separating corneal
      fibroblasts from bioactive substances in tear fluid. Exaggerated proliferation of
      and deposition of extracellular matrix by conjunctival fibroblasts likely
      exacerbate conjunctival inflammation. Restoration of an intact corneal epithelium
      and inhibition of the activities of corneal and conjunctival fibroblasts may
      provide a basis for the development of new treatments for severe ocular allergic
      diseases such as VKC.

PMID- 16427346
TI  - Genetic analysis in patients with left ventricular noncompaction and evidence for
      genetic heterogeneity.
AB  - Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by
      numerous excessively trabeculations and deep intertrabecular recesses. This study
      was performed to investigate Japanese LVNC patients for disease-causing mutations
      in a series of selected candidate genes. DNA was isolated from the peripheral
      blood of 79 cases including 20 familial cases and 59 sporadic cases. DNA samples
      were screened for mutations in the genes encoding G4.5 (TAZ), alpha-dystrobrevin
      (DTNA), alpha1-syntrophin (SNTA1), FK506 Binding protein 1A (FKBP1A or FKPB12:
      FKBP1A), and LIM Domain Binding protein 3 (Cypher/ZASP: LDB3), using single
      strand conformational polymorphism analysis and DNA sequencing. DNA variants were
      identified in 6 of the 79 cases, including four familial cases and two sporadic
      cases. A splice acceptor mutation of intron 8 in TAZ (IVS8-1G>C) was identified
      in one family with isolated LVNC, resulting in deletion of exon 9 from mRNA. In a
      sporadic case of isolated LVNC and Barth syndrome (BTHS), a 158insC in exon 2 of
      TAZ resulting in a frame-shift mutation was identified. A 1876G>A substitution
      changing an aspartic acid to asparagine (D626N) was identified in LDB3 in four
      members of two families with LVNC. A 163G>A polymorphism was identified in LDB3,
      which changed a valine to isoleucine (V55I) in one patient with isolated LVNC. In
      addition, in a family with nonisolated LVNC, a 362C>T mutation was identified in
      DTNA. LVNC, like other forms of inherited cardiomyopathy, is a genetically
      heterogeneous disease, associated with variable clinical symptoms and can be
      inherited as an autosomal or X-linked recessive disorder.

PMID- 16427348
TI  - Reaching hard-to-reach migrants by letters: an HIV/AIDS awareness programme in
      Nepal.
AB  - We assessed the impact of an HIV/AIDS programme for Nepalese migrants to India
      that involved writing letters. The programme created opportunities for sending
      HIV/AIDS-related messages to the migrants in India, and encouraging them
      practicing safer sex. Initially, they received the messages only from the
      programme, but later from their colleagues, spouses or other family members. They
      discussed the messages in groups, disseminated them, and sought more knowledge in
      their destinations. These findings indicated that using letters could be an
      effective way to reach inaccessible migrants at their destinations, and help them
      to improve their HIV/AIDS-related knowledge, and safer sex practices.

PMID- 16427350
TI  - Synthesis and two-dimensional correlation infrared spectroscopy study of an
      organic-inorganic hybrid compound constructed by [Mo(5)P(2)O(23)] and Cu
      imidazole components.
AB  - A novel compound, (Himi)(H(3)O) [Cu(imi)(2)](2)[P(2)Mo(5)O(23)].H(2)O 1
      (imi=imidazole), was synthesized by hydrothermal method and characterized by X
      ray single analysis, ESR spectrum, one-dimensional (1D) infrared spectroscopy and
      two-dimensional (2D) correlation infrared spectroscopy under thermal and
      magnetism perturbation. Crystal data for the compound 1: orthorhombic system,
      space group Pnma, a = 14.580(3)A, b = 21.073(4)A, c = 16.664(3)A, Z = 4. It
      consists of the Mo-Cu building-blocks [Cu(imi)(4)](2)[P(2)Mo(5)O(23)](2-),
      protonated imidazole cations and water molecules. In the Mo-Cu building-blocks,
      [Mo(5)P(2)O(23)](6-) clusters are linked by {Cu(imi)(4)}(2+) group to form a two
      dimension parallelogram griddling structure. From the 2D IR correlation
      spectroscopy analyses, it is discovered that the intensity changes of Mo=O and P
      O band are sensitive to the temperature variation, whereas the Mo-O bond linking
      to Cu(2+) can be remarkably affected by the magnetism variation. Furthermore, the
      intensity changes of P-O bands occur prior to that of the Mo=O band during the
      temperature elevation.

PMID- 16427351
TI  - Theoretical study of the changes in the vibrational characteristics arising from
      the hydrogen bonding between Vitamin C (L-ascorbic acid) and H2O.
AB  - The vibrational characteristics (vibrational frequencies, infrared intensities
      and Raman activities) for the hydrogen-bonded system of Vitamin C (L-ascorbic
      acid) with five water molecules have been predicted using ab initio SCF/6
      31G(d,p) calculations and DFT (BLYP) calculations with 6-31G(d,p) and 6
      31++G(d,p) basis sets. The changes in the vibrational characteristics from free
      monomers to a complex have been calculated. The ab initio and BLYP calculations
      show that the complexation between Vitamin C and five water molecules leads to
      large red shifts of the stretching vibrations for the monomer bonds involved in
      the hydrogen bonding and very strong increase in their IR intensity. The
      predicted frequency shifts for the stretching vibrations from Vitamin C taking
      part in the hydrogen bonding are up to -508 cm(-1). The magnitude of the
      wavenumber shifts is indicative of relatively strong OH...H hydrogen-bonded
      interactions. In the same time the IR intensity and Raman activity of these
      vibrations increase upon complexation. The IR intensity increases dramatically
      (up to 12 times) and Raman activity increases up to three times. The ab initio
      and BLYP calculations show, that the symmetric OH vibrations of water molecules
      are more sensitive to the complexation. The hydrogen bonding leads to very large
      red shifts of these vibrations and very strong increase in their IR intensity.
      The asymmetric OH stretching vibrations of water, free from hydrogen bonding are
      less sensitive to the complexation than the hydrogen-bonded symmetric OH
      stretching vibrations. The increases of the IR intensities for these vibrations
      are lower and red shifts are negligible.

PMID- 16427352
TI  - An ab initio study of the C2H2-HF, C2H(CH3)-HF and C2(CH3)2-HF hydrogen-bonded
      complexes.
AB  - MP2/6-31++G** and B3LYP/6-31++G** ab initio molecular orbital calculations have
      been performed in order to obtain molecular geometries, binding energies and
      vibrational properties of the C2H2-HF, C2H(CH3)-HF and C2(CH3)2-HF H-bonded
      complexes. As expected, the more pronounced effects on the structural properties
      of the isolated molecules due to complexation was verified for the C[triple
      bond]C and H-F bond lengths, which are directly involved in the H-bond formation.
      These bond distances increased after complexation. BSSE uncorrected B3LYP binding
      energies are always lower than the corresponding MP2 values. However, the
      opposite trend has been verified after BSSE correction by the counterpoise method
      since it is much lower at B3LYP than at MP2 level. The binding energies for these
      complexes as well as for the HF acid submolecule modes (the HF stretching and
      vibrational frequency modes) showed an increasing hydrogen-bonding strength with
      increasing methyl substitution. The splitting in the HF in-plane and out-of-plane
      bending modes reflects the anisotropy in the hydrogen-bonding interaction with
      the pi system of the C[triple bond]C bond. The H-F stretching frequency is
      shifted downward after complexation and it increases with the methyl
      substitution. The IR intensities of the HF acid submolecule fundamentals are
      adequately interpreted through the atomic polar tensor of the hydrogen atom using
      the charge-charge flux-overlap model. The skeletal stretching modes of the Alkyne
      submolecule are decreased in the complex. The new vibrational modes arising from
      complexation show several interesting features.

PMID- 16427353
TI  - Does alcohol increase the risk of hepatocellular carcinoma among patients with
      hepatitis C virus infection?
AB  - We conducted a hospital-based case-control study to investigate the effects of
      alcohol drinking on hepatocellular carcinoma (HCC) among patients with hepatitis
      C virus (HCV) infection, with special reference to the disease course and changes
      in drinking habits. From among 1159 HCV-RNA positive patients under clinical
      follow-up at Osaka City University Hospital (OCUH), we identified 73 cases newly
      diagnosed with HCC during the past 3 years and selected 253 matched controls
      without HCC. The odds ratios were calculated for cumulative and average daily
      ethanol consumption, during three different periods (lifetime, before, and after
      the first identification of liver disease), using a logistic regression model.
      Among all subjects, there was a trend towards an inverse association between HCC
      and lifetime ethanol consumption (P=0.059-0.066). The tendency was similar for
      ethanol consumption before the first identification of liver disease, while no
      associative trend was indicated after the first identification. Among those with
      minor changes on abdominal ultrasonography findings at the first OCUH visit, a
      positive association was suggested for ethanol intake after the first
      identification, although results were not statistically significant. In
      conclusion, our results did not demonstrate a strong positive association between
      alcohol drinking and HCV-related HCC in this population.

PMID- 16427354
TI  - The ACAT inhibitor avasimibe increases the fractional clearance rate of
      postprandial triglyceride-rich lipoproteins in miniature pigs.
AB  - Previously, we have shown, in vivo, that the acyl coenzyme A: cholesterol
      acyltransferase (ACAT) inhibitor avasimibe decreases hepatic apolipoprotein (apo)
      B secretion into plasma. To test the hypothesis that avasimibe modulates
      postprandial triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat
      load (2 g fat/kg) containing retinol was given to 9 control miniature pigs and to
      9 animals after 28 days treatment with avasimibe (10 mg/kg/day, n=5; 25
      mg/kg/day, n=4). The kinetic parameters for plasma retinyl palmitate (RP)
      metabolism were determined by multi-compartmental modeling using SAAM II.
      Avasimibe decreased the 2-h TRL (d<1.006 g/mL; S(f)>20) triglyceride
      concentrations by 34%. The TRL triglyceride 0-12 h area under the curve (AUC) was
      decreased by 21%. In contrast, avasimibe had no effect on peak TRL RP
      concentrations, time to peak, or its rate of appearance into plasma, however, the
      TRL RP 0-12 h AUC was decreased by 17%. Analysis of the RP kinetic parameters
      revealed that the TRL fractional clearance rate (FCR) was increased 1.4-fold with
      avasimibe. The TRL RP FCR was negatively correlated with very low density
      lipoprotein (VLDL) apoB production rate measured in the fasting state (r=-0.504).
      No significant changes in total intestinal lipid concentrations were observed.
      Thus, although avasimibe had no effect on intestinal TRL secretion, plasma TRL
      clearance was significantly increased; an effect that may relate to a decreased
      competition with hepatic VLDL for removal processes.

PMID- 16427355
TI  - Source localization of interictal epileptiform discharges: comparison of three
      different techniques to improve signal to noise ratio.
AB  - OBJECTIVE: To investigate the localization accuracy of low-resolution
      electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform
      discharges (IED) using a new relative averaging (RELAVG) technique for noise
      reduction. METHODS: We analyzed 19 patterns of mesial temporal IED recorded
      simultaneously with scalp and foramen ovale (FO) electrodes in 15 consecutive
      patients who underwent presurgical assessment for intractable temporal lobe
      epilepsy. The scalp signals were time-locked to the peak activity in the FO
      electrode recordings and source modeling was performed using the RELAVG
      technique. Random noise of various amounts was then applied. The results were
      compared to intracranial data obtained from the FO electrode recordings and to
      LORETA source solutions obtained using two other approaches to improve signal to
      noise ratio (SNR): statistical non-parametric mapping (SNPM) and the commonly
      applied averaging (AVG) technique. RESULTS: The RELAVG technique allowed for
      reasonable mesial temporal localization in 52.6% (10/19) of IED patterns,
      compared with 73.7% (14/19) using SNPM. The AVG technique provided no strictly
      mesial temporal solutions. Nine of the IED patterns revealed relative current
      density quotient changes >10; all of these were accurately localized by RELAVG
      into mesial temporal structures. Increasing amounts of white and physiological
      noise had no influence on the accuracy of RELAVG and SNPM solutions, whereas AVG
      source reconstructions became progressively spurious. CONCLUSION: The RELAVG
      technique and SNPM, but not the commonly used AVG technique, allow for reasonable
      source localization of mesial temporal IED. SNPM is the most accurate but also
      the most time-consuming noise reduction technique. SIGNIFICANCE: The RELAVG
      LORETA technique might provide a simple and fast semi-quantitative alternative
      for localizing IED with low single to noise ratio.

PMID- 16427356
TI  - Neck muscle fatigue and postural control in patients with whiplash injury.
AB  - OBJECTIVES: To examine if patients with whiplash injury show identifiable
      increases in neck muscle fatigability and associated increase in postural body
      sway after contractions of dorsal neck muscles, and if physiotherapy treatment
      reduces these effects. METHODS: Sway was measured during stance in 13 patients
      before and after 5 min of isometric dorsal neck muscle contractions and after
      recovery, pre- and post-physiotherapy, using a force platform. Amplitude and
      median frequency of neck muscle EMG were calculated during the contracting
      period. After each stance trial, patients gave a subjective score of sway.
      RESULTS: Pre-treatment, seven patients showed EMG signs of fatigue (increases in
      amplitude, decreases in median frequency) and increases in sway (eyes closed)
      after contractions. The other patients showed neither fatigue nor increased sway.
      Post-treatment, no signs of fatigue or imbalance were recorded in all patients,
      for the same levels of muscle contraction. CONCLUSIONS: As in normal human
      subjects, increases in sway are associated with signs of neck muscle fatigue in
      some whiplash injury patients. Physiotherapy decreases the susceptibility to
      fatigue of neck muscles and is an effective choice of treatment of subjective
      instability and sway. SIGNIFICANCE: This study demonstrates a pathophysiological
      link between neck muscle fatigue and impaired postural control, and also that
      physiotherapy can relieve symptoms and signs of impaired neck muscle function by
      reducing muscle fatigability.

PMID- 16427357
TI  - Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled
      clinical studies in brain stimulation.
AB  - OBJECTIVE: Brain polarization in the form of transcranial direct current
      stimulation (tDCS), which influences motor function and learning processes, has
      been proposed as an adjuvant strategy to enhance training effects in
      Neurorehabilitation. Proper testing in Neurorehabilitation requires double-blind
      sham-controlled study designs. Here, we evaluated the effects of tDCS and sham
      stimulation (SHAM) on healthy subjects and stroke patients' self-report measures
      of attention, fatigue, duration of elicited sensations and discomfort. METHODS:
      tDCS or SHAM was in all cases applied over the motor cortex. Attention, fatigue,
      and discomfort were self rated by study participants using visual analog scales.
      Duration of perceived sensations and the ability to distinguish tDCS from Sham
      sessions were determined. Investigators questioning the patients were blind to
      the intervention type. RESULTS: tDCS and SHAM elicited comparably minimal
      discomfort and duration of sensations in the absence of differences in attention
      or fatigue, and could not be distinguished from SHAM by study participants nor
      investigators. CONCLUSIONS: Successful blinding of subjects and investigators and
      ease of application simultaneously with training protocols supports the
      feasibility of using tDCS in double-blind, sham-controlled randomized trials in
      clinical Neurorehabilitation. SIGNIFICANCE: tDCS could evolve into a useful tool,
      in addition to TMS, to modulate cortical activity in Neurorehabilitation.

PMID- 16427358
TI  - Relationship between event-related beta synchronization and afferent inputs:
      analysis of finger movement and peripheral nerve stimulations.
AB  - OBJECTIVE: We compared beta synchronization associated with voluntary finger
      movement with beta synchronization produced by sensory stimulation, in order to
      better understand the relationship between event-related beta synchronization
      (ERS) and the different afferent inputs. METHODS: Twenty-four subjects performed
      an index finger extension. They also received three types of electrical
      stimulation (cutaneous stimulation of the index finger, single and repetitive
      stimulation of the median nerve). An EEG was recorded using 38 scalp electrodes.
      Beta ERS was analyzed with respect to movement offset and the stimulus (or the
      last stimulus in the series, for repetitive stimulation). RESULTS: Median nerve
      stimulation and finger extension induced more intense beta ERS than cutaneous
      stimulation. The magnitude of beta ERS induced by movement or by single median
      nerve stimulation were not different but post movement beta synchronization
      duration was longer than beta ERS induced by single median nerve stimulation and
      cutaneous stimulation. CONCLUSIONS: This study demonstrates that beta ERS depends
      on the type and quantity of the afferent input. SIGNIFICANCE: This work
      reinforces the hypothesis of a relationship between beta ERS and processing of
      afferent inputs.

PMID- 16427359
TI  - The membrane skeleton in Paramecium: Molecular characterization of a novel
      epiplasmin family and preliminary GFP expression results.
AB  - Previous attempts to identify the membrane skeleton of Paramecium cells have
      revealed a protein pattern that is both complex and specific. The most prominent
      structural elements, epiplasmic scales, are centered around ciliary units and are
      closely apposed to the cytoplasmic side of the inner alveolar membrane. We sought
      to characterize epiplasmic scale proteins (epiplasmins) at the molecular level.
      PCR approaches enabled the cloning and sequencing of two closely related genes by
      amplifications of sequences from a macronuclear genomic library. Using these two
      genes (EPI-1 and EPI-2), we have contributed to the annotation of the Paramecium
      tetraurelia macronuclear genome and identified 39 additional (paralogous)
      sequences. Two orthologous sequences were found in the Tetrahymena thermophila
      genome. Structural analysis of the 43 sequences indicates that the hallmark of
      this new multigenic family is a 79 aa domain flanked by two Q-, P- and V-rich
      stretches of sequence that are much more variable in amino-acid composition. Such
      features clearly distinguish members of the multigenic family from epiplasmic
      proteins previously sequenced in other ciliates. The expression of Green
      Fluorescent Protein (GFP)-tagged epiplasmin showed significant labeling of
      epiplasmic scales as well as oral structures. We expect that the GFP construct
      described herein will prove to be a useful tool for comparative subcellular
      localization of different putative epiplasmins in Paramecium.

PMID- 16427360
TI  - Sexuality as an aspect of nursing care for women receiving chemotherapy for
      breast cancer in an Irish context.

PMID- 16427361
TI  - Patients' knowledge regarding medication therapy and the association with health
      services utilization.
AB  - BACKGROUND: Upon discharge from the hospital, patients are significantly
      deficient in their knowledge of their medications. Provision of information has
      been shown to have an effect on health measures such as compliance to medication
      therapy, quality of life, and utilization of hospitalization services. AIMS: To
      assess patients' knowledge about their long term medication therapy and to
      measure the association between knowledge and health service utilization in the
      community. METHODS: A prospective study was performed, with home telephone
      interviews conducted 1 week and 1 month after discharge. The study population
      included 130 patients discharged to the community with new prescriptions for long
      term medications. RESULTS AND CONCLUSIONS: About 60% of the patients reported
      receiving no counseling regarding their new medication. About 30% utilized 3 or
      more types of service (family physician, specialist, nurse, etc.). Eighteen
      percent (18%) visited the ER during the month after discharge, of whom 35%
      visited twice or more. Higher levels of patient knowledge predicted higher levels
      of health services utilization (OR=4.76 95% CI: 1.74-13.06). The younger patients
      tended to utilize a larger variety of health services compared to the older
      patients (OR 0.32 95% CI: 0.13-0.79). The results of this study provide that
      patients with higher levels of knowledge utilized the health care system more
      often, perhaps indicating greater awareness and self care.

PMID- 16427362
TI  - A clonal cell line from immortalized olfactory ensheathing glia promotes
      functional recovery in the injured spinal cord.
AB  - Immortalized cell lines of olfactory ensheathing glia (OEG) that maintain the
      proregenerative properties of primary cultures provide an unlimited source of OEG
      for both basic and applied studies. Indeed, one specific immortalized rat OEG
      clonal line (TEG3) proved to be as good as primary OEG in promoting
      neuritogenesis and axon regeneration in culture models. Thus, we examined the
      capacity of TEG3 to promote axonal repair in an animal model of spinal cord
      injury, dorsal column crush. TEG3 cells can acquire astrocyte-like or Schwann
      cell-like morphology depending on the conditions under which they are cultured.
      In the injured spinal cord, prelabeled TEG3 survived for at least 10 weeks after
      grafting and they integrated into the spinal cord, adopting Schwann cell-like,
      astrocyte-like, or intermediate morphologies. In TEG3-transplanted animals,
      sensory projection axons grow into the lesion site and there was robust
      sprouting/axonal growth of the corticospinal tract, both into and beyond the
      lesion site, after crushing of the spinal cord-dorsal columns. TEG3-transplanted
      animals also recovered sensory and motor function in tape removal and beam
      walking behavioral tests. These data indicate that certain immortalized cell
      lines derived from a single cell can maintain the regenerative properties of
      primary OEG.

PMID- 16427363
TI  - Infective endocarditis complicated by large aortic pseudoaneurysm after cardiac
      surgery.
AB  - A 66-year-old female with Streptococcus viridans aortic and tricuspid infective
      endocarditis develops, during the course of antibiotic therapy, rupture of a
      right coronary sinus of Valsalva aneurysm to the right ventricle. An urgent
      cardiac surgery is preformed with implantation of a mechanical aortic prosthesis
      and a right coronary sinus plasty. Six months later a huge aortic pseudoaneurysm
      is diagnosed and she is submitted to a second uneventful surgery. A review is
      done for the significant features with discussion of diagnosis and therapy.

PMID- 16427364
TI  - The vanishing vast ventricular thrombus.
AB  - A 54-year old man presented with multiple pulmonary emboli and an incidental
      finding of a huge left ventricular thrombus. Transthoracic echo images
      demonstrated a globally dilated heart with very poor left ventricular function.
      It was elected to manage the patient medically, and he was commenced on warfarin
      therapy, resulting in completed resolution of the thrombus over 10 weeks. No
      underlying cause was found and he did not experience any further embolic events.
      This illustrates a rare case of a large ventricular thrombus in a patient with no
      underlying risk factors.

PMID- 16427365
TI  - Understanding African-American participation in a behavioral intervention:
      results from focus groups.
AB  - Heart failure (HF) is an increasingly prevalent condition contributing to
      significant morbidity and mortality among African-Americans. The Heart Failure
      Adherence and Retention Trial (HART) is the largest NHLBI funded behavioral
      clinical trial of patients with HF (R01 HL65547). The HART trial has recruited
      approximately 40% minority participants, with 33% being African-American. The
      purpose of this qualitative study is to conduct an in-depth examination of the
      subjective experience of African-American participants in the intervention arm of
      the HART. Five focus groups were conducted with a total of 25 participants. The
      mean age of those attending was 55 years, with a range between 39 and 82 years,
      52% of the participants were female, and 92% were African-American. Participants
      gained overall general medical knowledge about HF and how HF influenced their own
      lives. Participants appeared not only to understand the self-management skills
      that were taught; but also how to apply them. They also demonstrated
      understanding of the connection between lifestyle and HF. Factors that may
      promote retention include mutual support, the opportunity to engage in meaningful
      social activity, and feeling cared for. Factors that may limit retention include
      anxiety and denial about HF and logistical and emotional barriers to attending
      groups. Factors with unclear effects on retention include remuneration, ethnicity
      of the group leader, and the role of religious or spiritual content in meetings.
      While a number of perceived benefits exist to group participation, there are
      significant and logistical barriers to retention. Ongoing attention to cultural
      sensitivity is a likely factor in successful retention of study participants.

PMID- 16427366
TI  - Investigating placebo effects in irritable bowel syndrome: a novel research
      design.
AB  - Little is known about placebo effects with scientific precision. Poor methodology
      has confounded our understanding of the magnitude and even the existence of the
      placebo effect. Investigating placebo effects presents special research
      challenges including: the design of appropriate controls for studying placebo
      effects including separating such effects from natural history and regression to
      the mean, the need for large sample sizes to capture expected small effects, and
      the need to understand such potential effects from a patient's perspective. This
      article summarizes the methodology of an ongoing NIH-funded randomized controlled
      trial aimed at investigating whether the placebo effect in irritable bowel
      syndrome (IBS) exists and whether the magnitude of such an effect can be
      manipulated to vary in a manner analogous to "dose dependence." The trial also
      uses an innovative combination of quantitative and qualitative methods.

PMID- 16427367
TI  - Clubbing together on clamps: The key to translesion synthesis.
AB  - Translesion synthesis is an important mechanism by which cells replicate past DNA
      damage. The sliding clamp DNA polymerase processivity factors play a central role
      in this process. The clamps are dimeric in bacteria and trimeric in eukaryotes
      and archaea, raising the question of whether more than one polymerase can
      interact with the clamp simultaneously. Recently published data suggest that this
      is indeed the case.

PMID- 16427368
TI  - Simultaneous determination of urinary dialkylphosphate metabolites of
      organophosphorus pesticides using gas chromatography-mass spectrometry.
AB  - In this study, we developed a safe and sensitive method for the simultaneous
      determination of urinary dialkylphosphates (DAPs), metabolites of
      organophosphorus insecticides (OPs), including dimethylphosphate (DMP),
      diethylphosphate (DEP), dimethylthiophosphate (DMTP), and diethylthiophosphate
      (DETP), using a pentafluorobenzylbromide (PFBBr) derivatization and gas
      chromatography-mass spectrometry (GC-MS). Several parameters were investigated:
      pH on evaporation, reaction temperature and time for the derivatization, the use
      of an antioxidant for preventing oxidation, and a clean-up step. The pH was set
      at 6, adjusted with K2CO3, and the reaction temperature and time of
      derivatization were 80 degrees C and 30 min, respectively. Sodium disulfite was
      chosen as an antioxidant. The clean-up step was performed with a Florisil/PSE
      mini-column to remove the unreacted PFBBr and sample matrix. This established
      procedure markedly shortened the sample preparation time to only about 3 h, and
      completely inhibited the unwanted oxidization of dialkylthiophosphates. The
      limits of determination (LOD) were approximately 0.3 microg/L for DMP, and 0.1
      microg/L for DEP, DMTP, and DETP in 5 mL of human urine. Within-series and
      between-day imprecision for the present method using pooled urine spiked with
      DAPs was less than 20.6% in the calibration range of 1-300 microg/L, and the mean
      recovery was 56.7-60.5% for DMP, 78.5-82.7% for DEP, 88.3-103.9% for DMTP, and
      84.2-92.4% for DETP. This method detected geometric mean values of the urinary
      DAPs in Japanese with and without occupational exposure to OPs, 16.6 or 27.4 for
      DMP, 1.0 or 0.7 for DEP, 1.3 or 2.3 for DMTP, and 1.0 or 1.1 microg/L for DETP,
      respectively. The present method, which does not require special equipment except
      for GC-MS, is quick, safe, and sensitive enough to be adopted in routine
      biological monitoring of non-occupational as well as occupational exposure to
      OPs.

PMID- 16427369
TI  - Simple method for the quantitative analysis of endogenous folate catabolites p
      aminobenzoylglutamate (pABG) and its acetamido (apABG) derivative in human serum
      and urine by liquid chromatography-tandem mass spectrometry.
AB  - OBJECTIVE: To develop a routine method for quantitative measurement of the folate
      catabolites p-aminobenzoylglutamate (pABG) and acetamidobenzoylglutamate (apABG)
      in serum and urine using liquid chromatography-tandem mass spectrometry (LC
      MS/MS). DESIGN AND METHODS: Urine, serum and aqueous standards were thawed. Two
      microliters of d3-glutamic acid (d3-Glu; 1 mmol/L) was added to 200 uL of
      specimen as internal standard. The samples were acidified with 4 uL 6N HCL, and
      aliquots were precipitated with 2 volumes (412 uL) of acetonitrile. For urine
      specimens 30 volumes (6.18 mL) of acetonitrile was used. Samples were centrifuged
      at 1900 x g for 10 min and the supernatant (10 microL) injected into a Biorad
      CAT/MET analytical column fitted to the LC-MS/MS. Detection of the catabolites
      was by selective multiple ion monitoring (multiple SRM) of the respective
      transitions. Urine and serum samples were analysed in a group of healthy
      volunteers and in anonymous samples from patients being tested for PTH and
      urinary catecholamines. RESULTS: pABG and apABG eluted at 5.2 and 4.74 min,
      respectively while the d3-glutamic acid eluted at around 7 min. Limit of
      quantitation (LOQ) for both catabolites was 10 nmol/L (which is equivalent to
      33.3 fmol for a 10 microL injection). Limit of detection (LOD) was 1 nmol/L based
      on a signal to noise ratio of 5:1. A linear calibration curve was obtained from
      10 to 100 nmol/L for serum specimens and from 10 to 200 micromol/L for urines.
      Imprecision for spiked serum samples (n=10) was between 2.5 and 20% for apABG and
      4.5 and 21% for pABG (at 10 and 100 nmol/L, respectively). Imprecision for spiked
      urine samples (n=10) was between 2.9 and 4.0% for apABG and 6.0-12.7% for pABG.
      Recoveries were between 80 and 122% for serum samples and between 92 and 102% for
      urine specimens. Total folate catabolites in random urine samples from volunteers
      (n=5) are 2.9+/-2.3 umol/L (mean+/-S.D.). This group also had total serum
      catabolites of 11.9+/-7.6 nmol/L and serum folate of 35.3+/-5.8 nmol/L. Serum
      from patients being tested for PTH (n=11) had serum folate levels of 27.0+/-10.4
      nmol/L with total serum catabolites of 20.4+/-23.8 nmol/L. Levels of serum folate
      and total catabolites in pregnant women (n=18) were 33.9+/-22.7 and 11.4+/-8.7
      nmol/L, respectively. Mean urinary folate catabolites in patients being tested
      for urinary catecholamines (n=19) was 581.8+/-368.4 nmol/L. CONCLUSION: A simple,
      reliable and highly specific method by LC-MS/MS for detecting and quantifying the
      folate catabolites pABG and apABG was developed. This enables, for the first
      time, the routine clinical analysis of folate utilization in patients.

PMID- 16427370
TI  - Irritable bowel syndrome: What is the role of the psyche?

PMID- 16427371
TI  - Postnatal growth and bone mass in mice with IGF-I haploinsufficiency.
AB  - We examined the influence of IGF-I haploinsufficiency on growth, bone mass and
      osteoblast differentiation in Igf1 heterozygous knockout (HET) mice. Cohorts of
      male and female wild type (WT) and HET mice in the outbred CD-1 background were
      analyzed at 1, 2, 4, 8, 12, 15 and 18 months of age for body weight, serum IGF-I
      and bone morphometry. Compared to WT mice, HET mice had 20-30% lower serum IGF-I
      levels in both genders and in all age groups. Female HET mice showed significant
      reductions in body weight (10-20%), femur length (4-6%) and femoral bone mineral
      density (BMD) (7-12%) before 15 months of age. Male HET mice showed significant
      differences in all parameters at 2 months and thereafter. At 8 and 12 months, WT
      mice also showed a significant gender effect: despite their lower body weight,
      female mice had higher femoral BMD and femur length compared to males.
      Microcomputed tomography showed a significant reduction in cortical bone area (7
      20%) and periosteal circumference (5-13%) with no consistent pattern of change in
      trabecular bone measurements in 2- and 8-month old HET mice in both genders. HET
      primary osteoblast cultures showed a 40% reduction in IGF-I protein expression
      and a 50% decrease in IGF-I mRNA expression. Cell growth and proliferation were
      decreased in HET cultures. Thus, IGF-I haploinsufficiency in outbred male and
      female mice resulted in reduced body weight, femur length and areal BMD at most
      ages. Serum IGF-I levels showed a high level of positive correlation with body
      weight and skeletal morphometry. These studies show that IGF-I is a determinant
      of bone size and mass in postnatal life. We speculate that impaired osteoblast
      proliferation may contribute to the skeletal phenotype of mice with IGF-I
      haploinsufficiency.

PMID- 16427373
TI  - Inhibitors to Factor XI in patients with severe Factor XI deficiency.
AB  - Factor XI (FXI) deficiency is a rare bleeding disorder that may arise from any of
      a number of missense, nonsense, splice site, insertion, and deletion mutations
      within the FXI gene. Severely affected patients are at considerable risk of
      developing inhibitors to FXI and, although spontaneous bleeding is uncommon in
      such patients, bleeding after surgery or trauma can be severe. As treatment with
      fresh frozen plasma (FFP) or FXI concentrates is ineffective in patients with
      inhibitors, other therapies must be sought. Traditionally, such patients have
      been treated with various agents and methods, including plasma exchange,
      cyclophosphamide, intravenous immunoglobulin, and prothrombin complex
      concentrates. However, emerging data indicate that recombinant activated factor
      VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) may also be effective
      in FXI deficiency with inhibitors. Further work is required to determine the
      optimal dosing schedules of the agent in this indication.

PMID- 16427374
TI  - Advances in gene therapy using factor VIIa in hemophilia.
AB  - The development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo
      Nordisk, Bagsvaerd, Denmark) has provided an effective, alternative treatment
      strategy for hemophilia patients with inhibitors. However, its short half-life
      necessitates frequent infusions and results in high treatment costs. One
      potential solution to this problem may lie in the use of FVIIa gene transfer,
      which would achieve long-lasting therapeutic levels of expression from a single
      injection. Studies in animal models have shown that a recombinant adeno
      associated viral vector can be used to insert both murine and human FVIIa into
      murine liver. Following FVIIa gene transfer, mice with hemophilia B demonstrated
      a long-term, dose-dependent increase in circulating levels of FVIIa, reduced
      prothrombin time, and correction of activated partial thromboplastin time into
      the normal range. In addition, blood loss following a modified tail-clip assay
      was significantly reduced. Ongoing studies in mice engineered to express a wide
      range of FVIIa levels aim to analyze organ histology and evaluate long-term
      survival, reproductive fitness, and real-time in vivo clot formation in the
      microvasculature. These studies are expanding our knowledge of the effects of
      continuously expressed rFVIIa, and it is hoped that they may eventually provide a
      new avenue for treatment of hemophilia.

PMID- 16427375
TI  - Mechanism of action of recombinant activated factor VII: an update.
AB  - Bleeding episodes in patients with hemophilia and inhibitors must be managed
      using agents that are hemostatically active in the absence of factor VIII or IX.
      Activated prothrombin complex concentrates have long been used in this context.
      However, the search for safer and more effective agents has led to the
      development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk,
      Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of
      rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin
      production and thus contribute to the development of a stable, lysis-resistant
      fibrin plug at the site of vessel damage. This mechanism explains the reported
      efficacy of rFVIIa in a range of clinical situations characterized by impaired
      thrombin generation.

PMID- 16427377
TI  - Protein S multimers are generated in vitro and affect protein S structure
      function analyses.
AB  - Purified human protein S preparations contain small amounts of multimeric protein
      S. Protein S multimers are absent in plasma, suggesting that multimerization
      results from purification. Protein S multimers effectively inhibit phospholipid
      dependent reactions at low phospholipid concentrations, and may therefore
      interfere during functional analysis of protein S. We have demonstrated that
      anion-exchange chromatography, as well as high ionic strength or low pH elution
      conditions used in immunoaffinity purification of protein S, induce protein S
      multimer formation. When protein S multimers were removed from protein S
      preparations by size-exclusion chromatography, multimers spontaneously reappeared
      in the protein S monomer fraction. In model systems, high phospholipid
      concentrations (>50 micromol/L) completely abrogate the inhibitory effect of
      protein S multimers on prothrombinase complex activity. In addition, C4BP does
      not bind to protein S multimers. Thus, at low phospholipid concentrations,
      addition of C4BP to purified protein S will not affect the inhibitory activity of
      protein S multimers. In conclusion, to avoid misinterpretations during protein S
      structure-function analysis due to multimers present in purified protein S
      preparations, we recommend studying the anticoagulant activities of protein S
      either in plasma, where protein S is in its unmodified natural form, or at high
      phospholipid concentrations in model systems with purified proteins.

PMID- 16427376
TI  - High-dose recombinant factor VIIa therapy in hemophilia patients with inhibitors.
AB  - Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd,
      Denmark) is well established as an effective hemostatic agent for the management
      and prophylaxis of hemorrhage in hemophilia patients with inhibitors. Treatment
      schedules usually involve multiple bolus doses of 90 to 120 microg/kg
      administered every 2 to 3 hours, but recent evidence suggests that the use of
      higher doses might be justified. Such high-dose regimens may overcome the rapid
      clearance rate observed in pediatric patients, and may be more convenient for
      patients with poor venous access. It has been suggested that individually
      tailored high-dose therapies might be beneficial in selected groups of patients,
      although careful monitoring of such patients is advised. Thrombelastography has
      demonstrated considerable success in this regard, allowing accurate assessment of
      both hemostatic efficacy and individual response to rFVIIa. To date, no safety
      issues associated with high-dose rFVIIa have been identified. However, it is
      hoped that further research will support these favorable observations and thus
      contribute towards more effective dose optimization of rFVIIa in hemophilic
      inhibitor patients.

PMID- 16427378
TI  - Update on liver disease in hemophilia patients.
AB  - Prior to the introduction of viral inactivation techniques in the mid-1980s, the
      vast majority of patients with hemophilia who received plasma-derived clotting
      factor concentrates were exposed to and infected with the hepatitis C virus
      (HCV), a lipid-enveloped bloodborne pathogen. Hemophilia patients may also have
      been co-infected with the human immunodeficiency virus (HIV) after receiving
      contaminated blood products. HCV mono-infection has a very slow progression, but
      patients with hemophilia who are co-infected with HCV and HIV can exhibit a
      comparatively rapid progression of liver disease. Potential complications of
      chronic HCV infection are subsequent cirrhosis with hepatic failure and the
      ultimate onset of hepatocellular carcinoma. The treatment of either of these may
      involve orthotopic liver transplantation. Liver biopsy and morphologic evaluation
      of tissue remain the current "gold standard" by which the severity of HCV-induced
      liver disease can be reliably assessed. Although there has been a reluctance to
      perform invasive percutaneous liver biopsies in patients with hemophilia,
      available evidence suggests that they appear to be safe and they certainly
      provide greater specificity and sensitivity than radiographic techniques such as
      computerized tomography or magnetic resonance imaging. Treatment of HCV-infected
      patients is targeted towards preventing the progression of early cirrhosis and
      end-stage liver disease. The current standard of care for individuals with
      hemophilia has generally been considered to be the combination of standard
      interferon-alpha (IFN-alpha) with ribavirin for at least 6 months. Data
      concerning the use of PEGylated IFN, substituting for standard IFN-alpha, are now
      emerging, although relatively little of this information relates specifically to
      hemophilia patients with liver disease. Nevertheless, the favorable data from
      large non-hemophilia-related HCV disease with early cirrhosis have been
      extrapolated to the hemophilia scenario, and there has been no evidence in the
      limited number of hemophiliacs treated in this way to refute this conclusion.

PMID- 16427379
TI  - Pathogenesis of hemophilic arthropathy.
AB  - Intra-articular bleeding is the most common clinical manifestation of hemophilia,
      and can adversely affect joints and lead to arthropathy. Affected joints are
      associated with changes to the synovium, bone, cartilage and blood vessels. Iron
      plays a critical role in the pathogenesis of this condition, and may exert its
      effects through a variety of different mechanisms. Hemophilic arthropathy shares
      some injury characteristics with rheumatoid arthritis, although the degree of
      analogy is a matter of some debate. The influences of the mechanisms underlying
      joint inflammation are better understood for rheumatoid arthritis than for
      hemophilia, and it is hoped that this knowledge can be used to provide a more
      comprehensive knowledge of the pathological process of hemophilic arthropathy.
      This, in turn, may enable novel targets for therapeutic intervention to be
      identified.

PMID- 16427380
TI  - Surgery in hemophilia. The general view: patient selection, timing, and
      preoperative assessment.
AB  - Although often overlooked, the life of the patient with severe hemophilia is
      characterized by both intermittent and chronic pain. Bleeds into joints and
      muscles cause extensive pressure on sensory nerves and, following recurrent
      bleeds, joint destruction, and synovial reaction is accompanied by constant pains
      that are frequently mistaken for further bleeding. The orthopedic surgeon may
      break the vicious cycle of chronic synovitis by excising inflamed and
      hypertrophic synovium or severely damaged cartilage and adjacent bone ends, and
      implanting an artificial joint. Numerous technical solutions are now available
      and orthopedic surgery is increasingly on offer to those hemophilia patients who,
      since childhood, have been victims of insufficiently treated bleeds because no or
      limited treatment was available, and because the concept of prophylaxis had not
      yet been developed. Nonetheless, orthopedic surgery in patients with hemophilia
      requires much more effort and planning than surgery in non-hemophilic patients.
      In this overview, we will address issues related to surgery in hemophilic
      patients, as well as some practical issues related to the timing of surgery,
      preoperative testing, perioperative hemostasis, and patient rehabilitation.

PMID- 16427381
TI  - Functional assessment of arthropathy--an international perspective.
AB  - Treatment of hemophilia aims to minimize structural damage to joints and maximize
      patients' functional independence and quality of life. From an orthopedic
      perspective, treatment efficacy can be judged by quantifying the extent of
      musculoskeletal damage. Joint scores--both clinical and radiologic--have
      traditionally been measured in patients with hemophilia. However, such scores may
      lack the sensitivity to detect early changes in the hemophilic joint, and this
      has prompted the development of more sensitive measures. In addition, scores
      based on the status of individual joints do not consider the impact of
      arthropathy on overall musculoskeletal function. It would prove valuable to
      understand the implications of small differences in clinical/radiologic scores in
      terms of overall musculoskeletal function and patients' quality of life. The
      development of functional scores such as the Functional Independence Score for
      Haemophilia (FISH) and the Haemophilia Activities List (HAL), along with the
      quality-of-life (QoL) measurement tools, have helped to provide a more
      comprehensive assessment of health in hemophilia. Such improved understanding
      should assist with the development of contextually relevant guidelines for the
      management of hemophilia.

PMID- 16427382
TI  - Impact of choice of treatment for bleeding episodes on inhibitor outcome in
      patients with mild/moderate hemophilia a and inhibitors.
AB  - Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor
      VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline
      levels may remain stable for some patients, but may be reduced to less than 0.01
      U/mL for others. Several risk factors for the development of inhibitors in MHA
      have been proposed. Genetic factors, such as mutations in the FVIII gene, may
      play a central role; however, other influences, such as intensive treatment with
      FVIII products, may also be important. Optimal treatment regimens have yet to be
      determined, not only for the eradication of inhibitors, but also for the
      management or surgical prophylaxis of hemorrhages associated with this condition.
      Several treatment options for the control of bleeding in patients with MHA and
      inhibitors (MHAI) are currently available, and the choice of therapeutic strategy
      should be given careful consideration; some treatments may produce an anamnestic
      response, thus delaying the return to FVIII:C baseline levels and adversely
      affecting the duration of the severe bleeding phenotype. To increase our
      knowledge of MHAI, a retrospective collection of data is currently being
      performed among hemophilia centers in France and Belgium. Based on five examples
      of patients with MHAI collated from preliminary study data, we illustrate the
      impact on inhibitor outcome of the therapeutic choices used to treat bleeding
      episodes in these patients.

PMID- 16427384
TI  - Congenital and acquired platelet disorders: current dilemmas and treatment
      strategies.
AB  - Platelets are important for primary hemostasis. When a blood vessel is damaged,
      platelets adhere to exposed subendothelial connective tissue and form a
      hemostatic plug. Formation of the plug is contingent upon a series of processes,
      with adhesion, activation, and aggregation all being involved. Patients with
      quantitative platelet disorders have reduced numbers of platelets. Patients with
      qualitative disorders have platelets that exhibit abnormal functioning. Defects
      that impair function can affect platelet receptors, secretory responses, or
      intracellular signaling pathways. Examples of qualitative platelet disorders
      include Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome (BSS). The
      treatment of platelet disorders is primarily with platelet concentrates. However,
      in patients with abnormalities of their platelet surface receptors, platelet
      transfusion may provoke an immune response. Recombinant factor VIIa (rFVIIa) may
      provide hemostatically effective therapy in such patients.

PMID- 16427383
TI  - Glanzmann's thrombasthenia treatment: a prospective observational registry on the
      use of recombinant human activated factor VII and other hemostatic agents.
AB  - Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder caused by
      deficiency or dysfunction of platelet surface glycoprotein (GP) IIb/IIIa
      receptor. Platelet transfusion is the standard treatment for bleeding that
      remains non-responsive to conservative measures, and for surgical coverage.
      Platelet transfusions, however, may result in the development of antibodies to
      GPIIb/IIIa and/or human leukocyte antigen (HLA), rendering further transfusions
      ineffective. Recombinant human activated factor VII (rFVIIa; NovoSeven/Niastase
      [Canada], Novo Nordisk, Bagsvaerd, Denmark) has documented efficacy in GT
      patients, and is approved in the European Union for the treatment of GT patients
      with platelet antibodies and platelet refractoriness. However, there are
      insufficient data to determine the optimal rFVIIa regimen (eg, for major surgery)
      or to allow thorough safety evaluation (eg, thrombotic risk). A post-marketing,
      prospective, observational, multinational registry has been developed to collect
      data on the efficacy and safety of rFVIIa in the treatment and prevention of
      bleeding in GT patients with platelet antibodies or platelet refractoriness.
      Patients treated with other hemostatic agents or rFVIIa to avoid the development
      of antibodies against GPIIb/IIIa will also be reported. Standardized data will be
      collected using a customized internet-based (www.glanzmann-reg.org) data
      collection tool. Data collection will begin in 2005 and continue for up to 6
      years. Patients of all ages from any country are eligible for inclusion.

PMID- 16427385
TI  - Steps towards an effective treatment strategy in congenital factor VII
      deficiency.
AB  - Congenital factor VII (FVII) deficiency is a consequence of a genetic
      polymorphism that can produce a wide spectrum of disease severity. Mildly
      affected patients may experience increased bleeding after surgery, trauma or
      mucosal bleeding, while spontaneous and life-threatening bleeding occurs in
      patients who are severely affected. Replacement therapy is the mainstay of
      treatment for patients with FVII deficiency. This has traditionally been achieved
      using fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), or
      plasma-derived FVII concentrates. However, recombinant activated FVII is now
      widely used for therapy in these patients. As cases of FVII deficiency tend to be
      encountered infrequently in most centers, no consolidated evidence-based
      therapeutic regimens have evolved and the side effects of the available
      treatments have not been comprehensively evaluated. Consequently, an online
      registry, the Seven Treatment Evaluation Registry (STER) has been set up. This is
      a prospective study that aims to evaluate the efficacy and safety of the
      different therapeutic options with which FVII-deficient patients may be treated.
      Recruitment of patients into the study is currently underway.

PMID- 16427386
TI  - Acquired von Willebrand syndrome: an underdiagnosed and misdiagnosed bleeding
      complication in patients with lymphoproliferative and myeloproliferative
      disorders.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with
      laboratory findings similar to those for congenital von Willebrand disease (VWD).
      Unlike the congenital disease, AVWS usually occurs in individuals with no
      personal or family history of bleeding. The prevalence of AVWS in the general
      population is unknown because data from large prospective studies of this
      syndrome are not available. Although AVWS is particularly frequent in
      lymphoproliferative or myeloproliferative disorders, it can also be associated
      with solid tumors, immunologic and cardiovascular disorders, and other
      miscellaneous conditions. Diagnosis of AVWS is based on assays measuring the
      activity of von Willebrand factor (VWF). This tends to be abnormally low, but
      factor VIII (FVIII) coagulant activity can sometimes be normal. FVIII/VWF
      inhibiting activity is found in only a minority of cases. Bleeding episodes in
      patients with AVWS are mostly of the mucocutaneous type and can be managed with
      desmopressin, plasma-derived FVIII/VWF concentrates, and intravenous
      immunoglobulin (IVIg). Recombinant activated factor VII can be useful in patients
      unresponsive to standard therapy. An updated version of the International
      Registry on AVWS, recently available online, will provide more information on
      this rare, but underdiagnosed and misdiagnosed, disorder.

PMID- 16427387
TI  - Massive transfusion coagulopathy.
AB  - Coagulopathy following massive transfusion is a consequence of post-traumatic and
      surgical hemorrhage. Bleeding following massive transfusion can occur due to
      hypothermia, dilutional coagulopathy, platelet dysfunction, fibrinolysis, or
      hypofibrinogenemia. Transfusion of 15 to 20 units of blood products causes
      dilutional thrombocytopenia, and both antiplatelet agents (eg, clopidogrel
      [Plavix, Sanofi, Bridgewater, NJ]) and hemostatic inhibitors (eg, low-molecular
      weight heparins, pentasaccharides, and direct thrombin inhibitors) are
      contributing factors to bleeding. Tests for platelet dysfunction are not readily
      available. Excessive fibrinolysis and low fibrinogen are also causes of bleeding
      in these patients. Currently, however, there are several agents that have been
      reported to be effective for the prophylaxis of hemorrhage in surgical patients,
      including aprotinin for cardiac surgery, orthopedic surgery, and hepatic
      transplantation, and the off-label use of recombinant activated factor VII
      (NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) as rescue therapy for life
      threatening hemorrhage.

PMID- 16427388
TI  - Assessing efficacy and therapeutic claims in emerging indications for recombinant
      factor VIIa: regulatory perspectives.
AB  - When compared with the evidence-based, cost-effectiveness criteria underpinning
      most government reimbursement schemes in the social market economies, the three
      regulatory hurdles of safety, quality and efficacy are probably of modest impact
      in influencing increased usage of recombinant activated factor VII (rFVIIa;
      NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Nevertheless, efficacy claims must
      be supported if regulatory approval is to be granted for the wider range of
      indications that have been proposed for rFVIIa. With the refinement of clinical
      trial designs over the past 40 years, the randomized controlled trial (RCT) has
      assumed the role of gold standard, providing the highest level of evidence for
      therapeutic efficacy. However, it is incorrect to assume that regulatory
      authorities give sole credence to RCTs in assessing claims. It is noteworthy that
      the indications already accepted for rFVIIa by international regulatory
      authorities--including the treatment of inhibitors to factor VIII and factor IX,
      substitution for FVII deficiency, and treatment of Glanzmann's thrombasthenia-
      were supported not by RCTs but by studies conventionally considered to provide
      modest evidence levels. Therefore, the use of studies other than RCTs for the
      more recently proposed indications for rFVIIa in a range of conditions requiring
      hemostatic correction is perfectly feasible. What regulators expect are well
      conducted and well-described studies adhering to principles of good clinical
      practice, which can be scrutinized for evidence of clinical efficacy and which
      are based on the initially proven principle for the drug. This paper discusses
      the regulatory history of rFVIIa in the major regulatory authorities and assesses
      the route needed to support claims being made in the mainstream literature.
      Recent episodes where post-market events have forced regulators to be more than
      usually cautious will be used as examples to suggest possible pitfalls to the
      extension of approved claims for rFVIIa. The major paths for enhancing access for
      indications in small patient numbers, where RCTs are even more difficult to
      perform, will be described and their use for possible extension of rFVIIa
      indications will be discussed.

PMID- 16427389
TI  - Ultra-early hemostatic therapy for acute intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is the least treatable form of stroke, and causes
      high mortality, severe disability, and a staggering economic burden. ICH accounts
      for 15% of stroke cases in the United States and Europe, and up to 30% in Asian
      populations. Computed tomography-based studies suggest that ICH growth within the
      first few hours of onset is common, and the principal cause of early neurological
      deterioration. Hematoma volume is also a well-established predictor of 30-day
      mortality. Intervention with ultra-early hemostatic therapy could minimize or
      prevent this early dynamic bleeding process, and might improve outcome.
      Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd,
      Denmark) is approved for the treatment of bleeding in patients with hemophilia
      and inhibitors, but it may also promote hemostasis in patients with normal
      coagulation by acting locally at the bleeding site without activation of systemic
      coagulation. In a randomized, double-blind, placebo-controlled trial of 399 ICH
      patients treated with a single dose of 40, 80, or 160 microg/kg of rFVIIa or
      placebo within 4 hours of onset, subsequent hematoma growth was reduced by
      approximately 50% with rFVIIa. This was associated with a significant reduction
      (38%) in mortality, and improved functional outcomes among survivors. A phase III
      trial comparing 20 and 80 microg/kg rFVIIa with placebo is now in progress to
      confirm these results.

PMID- 16427390
TI  - New anti-thrombotic agents: emphasis on hemorrhagic complications and their
      management.
AB  - Our advanced knowledge of coagulation has led to the synthesis of novel
      procoagulant substances, such as recombinant activated factor VII (rFVIIa;
      NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). Similarly, in-depth understanding
      of the interaction between anticoagulant proteins and their natural inhibitors
      has led to the synthesis of various novel anticoagulants. Novel anticoagulants
      are characterized by highly specific coagulation-inhibiting activities and,
      frequently, a complete lack of effective antidotes. This lack of antidotes is
      particularly important in the case of novel inhibitors with extended half-lives;
      for example, idraparinux may produce effective anticoagulation for as long as one
      week after subcutaneous administration. As novel anticoagulants complete
      licensing evaluations and are used in clinical practice, the likelihood of
      anticoagulant-associated hemorrhage will increase. This will require physicians
      to have an understanding of the mechanism of action of these anticoagulants, and
      to have an advanced degree of knowledge of the potential specific and nonspecific
      inhibitors of these anticoagulant agents. This paper will briefly review the
      biochemistry of coagulation, focusing on the complexes inhibited by currently
      available and novel anticoagulants. Specific and nonspecific prohemostatic agents
      will be reviewed and discussed. The ability of nonspecific procoagulant agents
      (particularly rFVIIa) to reverse the effects of novel anticoagulants will also be
      reviewed.

PMID- 16427391
TI  - Milestones in hemophilia and concepts in future clinical trial design.
AB  - Hemophilia has long been documented as a bleeding disorder that afflicts males
      from early childhood. While some early societies set guidelines or laws to
      protect affected children, true advances in the understanding of the underlying
      deficiency and in the treatment of hemophilia have been relatively recent and
      continue today. This paper presents some of the key milestones that mark the path
      to current knowledge on hemophilia. Given that further studies are needed to
      explore issues such as optimal treatment and dosage, particularly in patients
      with inhibitors to factor VIII or factor IX, this paper also considers potential
      pitfalls in the design and conduct of clinical trials in hemophilia and suggests
      how careful forward planning may help to avoid them.

PMID- 16427394
TI  - Chemotherapy for glioblastoma multiforme (GBM).

PMID- 16427392
TI  - The platelet: form and function.
AB  - Platelets are small subcellular fragments that are released from megakaryocytes.
      They are composed of a concentrate of megakaryocyte membrane, cytoplasm,
      granules, and organelles, and circulate throughout blood vessels and survey the
      integrity of the vascular system. They circulate as discs, a form specified by
      their internal microtubule and actin cytoskeleton. When encountering vascular
      damage, platelets rapidly convert into their active forms, which function to seal
      off the injury and prevent fluid loss. To assume the active shape, the internal
      cytoskeleton of each platelet is rapidly disassembled and replaced. New actin
      filament assembly provides the force that spreads platelets across damaged
      surfaces and allows the formation of filopodia, which are used to interconnect
      platelets in solution. In this review, we discuss the role of the cytoskeleton in
      defining the resting and active forms of the platelet.

PMID- 16427395
TI  - You are going to live to 120 years of age!

PMID- 16427399
TI  - Clinical evaluation of traumatic central cord syndrome: emphasis on clinical
      significance of prevertebral hyperintensity, cord compression, and intramedullary
      high-signal intensity on magnetic resonance imaging.
AB  - BACKGROUND: We evaluated the prognostic and clinical value of radiological
      findings including prevertebral hyperintensity (HI), cord compression,
      intramedullary high-signal intensity (IMHSI) and instability in patients with
      traumatic central cord syndrome without evidence of fracture and dislocation.
      METHODS: The radiological and clinical findings of 23 patients who had undergone
      surgery between 1996 and 2002 were reviewed retrospectively. All of the patients
      underwent dynamic motion study and magnetic resonance (MR) imaging after trauma.
      Neurologic status was evaluated with American Spinal Injury Association motor
      score pre- and postoperatively and compared with the radiological findings.
      Anterior decompression and fusion were performed in 12 patients with 1- or 2
      level lesions, and posterior decompression was done for 11 cases of multilevel
      lesions. RESULTS: Prevertebral HI was found in 17 patients. Among them,
      instability was revealed in 11 patients. There was significant correlation
      between prevertebral HI and instability (P = .014). Cord compression was found in
      varying degrees in all patients on MR imaging. Intramedullary high-signal
      intensity was found preoperatively in 19 (83%) of 23 patients, and it was
      revealed at the most compressed level of the spinal cord in all cases. The
      neurologic level was consistent with the level of instability (100%), IMHSI
      (95%), and cord compression (87%). Mean American Spinal Injury Association motor
      scores in patients with instability were lower than in those without instability
      (P < .05). CONCLUSIONS: The presence of prevertebral HI, IMHSI, and cord
      compression influenced the neurologic status of the patients. The instability was
      significantly associated with poor prognosis for neurologic outcome. Prevertebral
      HI on T2 MR imaging may be a possible indicator of instability in patients with
      central cord syndrome after hyperextension injury.

PMID- 16427396
TI  - Retroperitoneal approach for lumbar interbody fusion with anterolateral
      instrumentation for treatment of spondylolisthesis and degenerative foraminal
      stenosis.
AB  - BACKGROUND: An alternative approach for the treatment of the degenerative or
      unstable lumbar spine using retroperitoneal lateral LIF with anterolateral screw
      plate or screw-rod fixation is introduced. Special attention is given to
      application of this procedure in patients who have undergone prior lumbar
      surgery. METHODS: Between 1998 and 2001, 14 patients underwent lateral LIF with
      anterolateral instrumentation to treat degenerative foraminal stenosis or
      spondylolisthesis. Eleven patients (79%) had undergone prior posterior lumbar
      surgery, 7 of whom were also fused at that time. All patients first presented
      with mechanical back pain, radicular pain, or both. The mean follow-up was 21
      months (range, 8 to 36 months). RESULTS: Radicular pain and mechanical back pain
      significantly improved in 71% and 54% of patients, respectively. Of the 9
      patients with preoperative neurological deficits, 7 were intact or had improved
      at their follow-up examination. One patient developed postoperative radiculopathy
      contralateral to his original symptoms. Radiography confirmed good positioning of
      the hardware and evidence of fusion in all 14 patients. No major complications
      occurred. CONCLUSIONS: Retroperitoneal lateral LIF with anterolateral
      instrumentation is an attractive alternative for the treatment of the
      degenerative or unstable lumbar spine in the absence of significant spinal
      stenosis. This approach is particularly useful for treating spondylolisthesis or
      degenerative foraminal stenosis in the postoperative lumbar spine.

PMID- 16427400
TI  - Pineal epidermoid cysts: a study of 24 cases.
AB  - BACKGROUND: A retrospective analysis of clinical features and management strategy
      in 24 cases of epidermoids in the pineal region is done. Long-term outcome of
      radical surgical resection is analyzed. METHODS: Twenty-four patients having
      epidermoids in the pineal region were surgically treated in our department during
      an 11-year period (1992 up to 2003). These cases were retrospectively analyzed.
      The average duration of follow-up was 5.2 years. RESULTS: The age at the time of
      presentation ranged from 13 to 51 years (mean, 29.2 years). There were 15 male
      and 9 female patients. The average duration of complaints was 7 months. Headache
      and ataxia were the commonest symptoms. The infratentorial-supracerebellar
      approach and the interhemispheric posterior parietooccipital route were used to
      excise the epidermoids in 20 and 3 patients, respectively. In one patient, the
      tumor was removed in 2 stages, first by the infratentorial-supracerebellar
      approach and subsequently by the interhemispheric posterior parietooccipital
      surgical approach. Total excision of the solid part of the tumor and the capsule
      was achieved in 6 patients. In 13 cases, the solid part of the tumor was
      completely resected, but at least, a part of the tumor capsule was left behind.
      In 5 cases, a part of the solid portion of the tumor was either deliberately or
      inadvertently left behind. Incomplete tumor resection was primarily due to
      adhesions of the capsule to large veins in the region, dissection around which
      was considered hazardous, and extensive and invasive nature of extension of the
      tumor. During the period of follow-up, one patient had asymptomatic growth of the
      residual tumor after 6 years of surgery. One patient with residual tumor
      continued to get generalized seizures. All patients are leading active lives.
      CONCLUSION: Radical surgery for pineal region epidermoid tumors is associated
      with an excellent immediate postoperative and long-term outcome.

PMID- 16427401
TI  - Evaluation of magnetic resonance imaging criteria for cavernous sinus invasion in
      patients with pituitary adenomas: logistic regression analysis and correlation
      with surgical findings.
AB  - BACKGROUND: This study used high-resolution magnetic resonance (MR) imaging (1.5
      T) to define and evaluate preoperative imaging criteria for cavernous sinus
      invasion (CSI) by pituitary adenoma (PA). METHODS: Magnetic resonance images
      obtained from 103 patients with PA submitted to surgery (48 with CSI) were
      retrospectively reviewed. The following MR signs were studied and compared with
      intraoperative findings: (1) presence of normal pituitary gland between the
      adenoma and cavernous sinus (CS), (2) status of the CS venous compartments, (3)
      CS size, (4) CS lateral wall bulging, (5) displacement of the intracavernous
      internal carotid artery (ICA) by adenoma, (6) grade of parasellar extension
      (Knosp-Steiner classification), and (7) percentage of intracavernous ICA encased
      by the tumor. Statistical analysis was performed using chi2 testing, and
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were obtained for each MR finding. The odds ratio of the
      most significant criteria was also obtained, and the multiple logistic regression
      test was used to compare the criteria altogether. RESULTS: The following signs
      have been found to represent accurate criteria for noninvasion of the CS: (1)
      normal pituitary gland interposed between the adenoma and the CS (PPV, 100.0%),
      (2) intact medial venous compartment (PPV, 100.0%), and (3) percentage of
      encasement of the intracavernous ICA lower than 25% (NPV, 100.0%). Cavernous
      sinus invasion was certain if the percentage of encasement of the intracavernous
      ICA was higher than 45% and 3 or more CS venous compartments were not depicted.
      The most valuable criterion of CSI by logistic regression analysis was the
      percentage of encasement of intracavernous ICA of 30% or more, with an odds ratio
      of 49.25. CONCLUSION: The preoperative diagnosis of CSI by PA is extremely
      important because endocrinologic remission is rarely obtained after microsurgery
      alone in patients with invasive tumors. The aforementioned MR imaging criteria
      may be useful in patient's management and in advising most of the patients
      preoperatively on the potential need for complimentary therapy after surgery.

PMID- 16427404
TI  - Nonsuture dural repair using polyglycolic acid mesh and fibrin glue: clinical
      application to spinal surgery.
AB  - BACKGROUND: In spinal surgery, repair of the dura is difficult when it is torn or
      fragile or is ossified as in cases with ossification of posterior longitudinal
      ligament. We report our experience with a nonsuture dural repair technique in
      patients undergoing spinal surgery; it uses a dura substitute composed of
      polyglycolic acid (PGA) mesh and fibrin glue. Here, we report the efficacy and
      safety of nonsuture duroplasty using PGA mesh and fibrin glue (PGA-fibrin sheet).
      METHODS: The artificial dura mater is composed of a PGA-fibrin sheet. The dural
      defect is covered with a patch sprayed with fibrin glue without suturing to the
      dura mater. We first evaluated this technique in an experimental study by
      performing water leakage tests. Between May 2001 and January 2005, we used it in
      160 spinal surgeries that required intraoperative dura repair. RESULTS: Our
      preliminary tests showed that the threshold for water pressure without leakage
      was 161 +/- 42 and 96.5 +/- 32 mm Hg when the unsprayed margin around the
      perimeter of the patch was 5 and 2 mm, respectively. Of the 160 operated
      patients, 10 (6.3%) experienced subcutaneous cerebrospinal fluid (CSF) leakage.
      Of these, 6 required a second operation; in the other 4, the CSF collection
      diminished spontaneously. There were no other complications such as allergic
      reaction, adhesion, or infection. CONCLUSION: In combination with CSF diversion,
      the PGA-fibrin sheet is a viable alternative method for dural repair in spinal
      surgery.

PMID- 16427407
TI  - Use of equine collagen foil as dura mater substitute in endoscopic endonasal
      transsphenoidal surgery.
AB  - OBJECTIVE: This study describes the use of a novel collagen-based dural
      substitute in endoscopic endonasal transsphenoidal surgery. METHODS: Operative
      records were reviewed for a 12-month period for all patients who underwent
      surgery by means of an endoscopic endonasal transsphenoidal approach since we
      began using TissuDura (Baxter, Vienna, Austria) collagen-only dural substitute in
      January 2004. RESULTS: During the 12-month period evaluated, we performed an
      endoscopic endonasal transsphenoidal operation for a variety of pituitary lesions
      on 72 consecutive patients. Among these, 15 patients (20.8%) required the implant
      of the collagen foil. Nine patients (60%) presented an intraoperative CSF leak (3
      small weeping of CSF and 6 larger leaks); in these cases, the TissuDura was used
      against the arachnoid membrane, followed by the other materials used for the
      repair. In 7 other subjects without any evidence of CSF escape, the collagen foil
      was used to protect and enforce the arachnoidal membrane descent into the sellar
      cavity to prevent its possible postoperative rupture and consequent CSF leak.
      Fibrin glue was used in all cases. A postoperative CSF leak with meningitis
      occurred in only 1 (6.7%) of the 15 subjects. The patient required a reoperation
      for CSF fistula repair and intravenous antibiotics. CONCLUSIONS: Even if based on
      a relatively small patient series, our experience demonstrated that the use of
      TissuDura in transsphenoidal surgery is safe and biocompatible, as compared with
      other dural substitutes.

PMID- 16427412
TI  - Microsurgical anatomy of the anterior communicating artery complex in adult
      Chinese heads.
AB  - BACKGROUND: The anterior communicating artery complex, which is composed of
      anterior cerebral artery (ACA), anterior communicating artery (ACoA), and
      recurrent artery of Heubner, accounts for the anterior half of the circle of
      Willis and is a favorite site of aneurysm formation; ACoA accounts for most of
      intracranial aneurysms. Few authors have studied the microanatomy of the ACA in
      detail using different specimens; none of these studies involve Chinese specimen.
      We have studied this area on adult Chinese brain with the aid of surgical
      microscope. METHODS: The anterior communicating artery complexes of 90 cerebral
      hemispheres from 45 formalin-fixed cadavers were dissected under microscope.
      RESULTS: The length and diameter of the recurrent artery and their perforating
      branches were measured. Their supplying areas, the adjacent structures, and their
      variations were also recorded. CONCLUSION: The cerebral vessels of native people
      have many variations in structure. The result of this study is quite different
      from that of the foreign literatures. The microanatomy of cerebral vessels also
      provides important data in its morphology for neurosurgeons.

PMID- 16427409
TI  - Bedside twist drill craniostomy for chronic subdural hematoma: a comparative
      study.
AB  - BACKGROUND: Although the bedside twist drill craniostomy is used to treat chronic
      subdural hematomas, the efficacy of this technique has not been compared with
      that of standard treatments (operative bur hole or craniotomy). METHODS: Twist
      drill craniostomy was compared with operative bur hole or craniotomy in a
      prospective nonrandomized trial. The inclusion criteria were computed tomographic
      evidence of chronic subdural hematoma (isodense or hypodense compared with brain)
      and symptoms indicating the need for drainage. Selection of the procedure
      depended on the on-call surgeon's preference. Clinical success of the procedure,
      recurrence, length of hospitalization, complications, and neurologic outcome were
      compared. RESULTS: Between August 2001 and October 2002, 79 consecutive patients
      with 91 chronic subdural hematomas were treated (67 unilateral and 12 bilateral)
      at our institution. Fifty-five patients were treated with twist drill craniostomy
      and 24 with bur hole or craniotomy. There were no differences in the mean age of
      presentation, thickness of hematoma, length of hospitalization, reoperation rate,
      mortality rates, or ability to be discharged to home between the 2 groups. There
      was no difference in the neurologic outcomes in the 57 of the 79 patients
      available for follow-up. CONCLUSIONS: Twist drill craniostomy performed at the
      bedside is just as effective in treating chronic subdural hematomas as bur holes
      or craniotomy in the operating room. This procedure can most often be the first
      line of treatment in patients with symptomatic chronic subdural hematomas.

PMID- 16427414
TI  - Type I congenital multiple intraspinal extradural cysts associated with
      distichiasis and lymphedema syndrome.
AB  - OBJECTIVE: The hereditary syndrome of multiple congenital intraspinal cysts
      associated with distichiasis, lymphedema and other congenital deformities is
      extremely rare. Modern imaging techniques have promoted the non-invasive
      diagnosis of spinal pathology and paved the way for better surgical planning. We
      reviewed the clinical data, imaging studies and treatment outcomes of a 12-year
      old boy with this syndrome. CLINICAL PRESENTATION: Progressive spastic
      paraparesis with signs of spinal cord compression leading to frequent falls. This
      was associated with bilateral double row of eyelashes and pretibial edema. The
      MRI of thoracic spine depicted two large elongated extradural lesions extending
      from D5-D10 with signal intensity compatible with cerebrospinal fluid leading to
      severe compression of the spinal cord dorsally. TREATMENT: Laminotomy and
      complete microsurgical excision of the cysts resulted in a fast and full clinical
      recovery of his neurological deficit. CONCLUSION: Type I congenital intraspinal
      cysts is a rare etiology of cord compression syndrome and may be associated with
      distichiasis, lymphedema and other congenital deformaties. It has several
      characteristics, which include the higher incidence in thoracic spine and younger
      age group, disproportional sever motor deficit as compared with sensory
      disturbances and the excellent clinical recovery following successful surgical
      treatment.

PMID- 16427415
TI  - Transient memory disturbance after removal of an intraventricular trigonal
      meningioma by a parieto-occipital interhemispheric precuneus approach: Case
      report.
AB  - BACKGROUND: Pitfalls in a parieto-occipital interhemispheric precuneus approach
      for the ventricular trigonal region of a dominant hemisphere have been rarely
      reported. We described a case with memory disturbance after surgery using this
      approach. CASE DESCRIPTION: A 57-year-old, right-handed woman complained of
      numbness of the lower extremities and underwent magnetic resonance imaging, which
      incidentally demonstrated a trigonal meningioma in the left lateral ventricle
      with a maximal diameter of 4 cm. The patient's preoperative neurologic
      examination was normal. The tumor was successfully removed by a parieto-occipital
      interhemispheric approach with an incision of the left precuneus cortex.
      Postoperative motor, sensory, and visual functions were normal; however, recent
      memory disturbance developed, which gradually resolved in the following 3 months.
      CONCLUSIONS: An interhemispheric precuneus approach is a useful alternative to
      trigonal tumors with few surgical complications, but postoperative memory
      disturbance can be one pitfall of this procedure.

PMID- 16427416
TI  - Parry-Romberg syndrome with a giant internal carotid artery aneurysm.
AB  - BACKGROUND: Parry-Romberg syndrome or progressive facial hemiatrophy is a rare
      clinical entity of an unknown etiology. We present the case of a 56-year-old
      woman with Parry-Romberg syndrome and a giant internal carotid artery aneurysm.
      CASE DESCRIPTION: The case was a 56-year-old woman with Parry-Romberg syndrome
      and a giant internal carotid artery aneurysm. Its association was extremely rare.
      Our report and some other reports of Parry-Romberg syndrome with cerebral
      aneurysms suggest the hypothesis that Parry-Romberg syndrome could be related to
      some inflammatory causes such as an autoimmune disease. CONCLUSION: We present
      the case of a 56-year-old woman with Parry-Romberg syndrome and a giant internal
      carotid artery aneurysm. Its association is extremely rare and will support the
      hypothesis that Parry-Romberg syndrome could be related to some inflammatory
      causes such as an autoimmune disease.

PMID- 16427417
TI  - Neuroenteric cyst of the anterior cranial fossa: case report and review of the
      literature.
AB  - A case of intradural neuroenteric cyst located in the anterior cranial fossa is
      presented. The cyst caused anosmia and progressive personality changes in an
      elderly woman. The patient underwent bifrontal craniotomy with evacuation of cyst
      contents and removal of the cyst wall. Incidence, classification, histopathology,
      and histogenesis of neuroenteric cysts are discussed with review of the
      literature.

PMID- 16427419
TI  - Sterile recurrent spinal epidural abscess in a patient with Crohn's disease: a
      case report.
AB  - BACKGROUND: The frequency of SEA is increasing. There are several well
      established predisposing factors. CASE DESCRIPTION: Our case presents certain
      unusual features that include an association with CD, persistent sterile
      cultures, and multiple recurrences of lesions at adjacent levels. CONCLUSIONS: A
      review of the literature showed only 13 case reports of SEA in patients with CD
      with an additional patient mentioned in one series. Recurrence of SEA at the same
      location was reported only twice. The diagnostic workup and treatment modalities
      pertinent to this case are discussed.

PMID- 16427421
TI  - Intramedullary spinal tuberculoma: report of three cases.
AB  - BACKGROUND: Intramedullary spinal tuberculoma is a rare form of central nervous
      system tuberculosis. This article describes the successful management of
      intramedullary spinal tuberculoma in 3 patients who received treatment between
      2000 and 2003. CASE DESCRIPTION: The character of 3 cases was analyzed
      retrospectively, including clinical manifestation and magnetic resonance imaging
      findings. All masses were excised totally under microscope. Histopathologic
      examination revealed tuberculoma. Postoperatively, all patients received a 6 to 9
      month course of ATT. The outcome was favorable. CONCLUSIONS: The intramedullary
      spinal tuberculoma must be considered in the differential diagnosis of the spinal
      cord compression in patients with a history of tuberculosis. When confronted with
      a progressing neurologic deficit and poor response to ATT, surgical intervention
      should be considered. The optimal treatment is a combination of microsurgical
      resection and ATT.

PMID- 16427423
TI  - Treatment of unruptured duplicated middle cerebral artery aneurysm: case report.
AB  - BACKGROUND: Duplication of the middle cerebral artery (DMCA) is an anomalous
      vessel arising from the internal carotid artery (ICA). The origin of the DMCA
      lies between the anterior choroidal artery and the distal end of the ICA. The
      association of cerebral aneurysm and DMCA is rare. CASE DESCRIPTION: In this 63
      year-old woman, preoperative angiography and 3-dimensional computed tomography
      angiography revealed an aneurysm at the origin of the DMCA. The aneurysm was
      clipped and superficial temporal artery-DMCA anastomosis was performed. She was
      discharged with no neurologic deficits. Duplication of the middle cerebral artery
      can be divided into 2 types based on whether the site of separation from the ICA
      is at the top of the ICA (type A) or between the ICA top and the anterior
      choroidal artery (type B). The diameter of type A DMCA is comparable with that of
      the main middle cerebral artery trunk; in type B, it is smaller. In all 18
      previously reported cases, the aneurysm was associated with type B DMCA.
      CONCLUSION: For appropriate treatment planning, it is necessary to determine the
      DMCA type and the anatomic relationship between the aneurysm and the DMCA. In
      patients with type B DMCA, the possibility of aneurysm formation should be
      considered.

PMID- 16427428
TI  - Basilar megadolicho trunk causing obstructive hydrocephalus at the foramina of
      Monro.
AB  - We report on a 54-year-old man with megadolicho basilar artery presenting with
      acute signs of raised intracranial pressure due to a compromise of cerebrospinal
      fluid (CSF) flow at the level of the foramina of Monro by the basilar apex
      extending more than 3 cm cranially to the dorsum sellae. The diagnosis was
      confirmed on computed tomographic angiography and emergent CSF drainage relieved
      symptoms immediately.

PMID- 16427426
TI  - Assessment of sacrum scalloping in neurofibromatosis type 1 caused by a giant
      cell lesion of the sacrum.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF-1) is the most common of the
      neurocutaneous disorders. It leads to significant orthopedic complications and
      spinal deformities. Scalloping in NF-1 may be caused by weakness of the
      mesodermal dysplasia, which develops through the inherited mutation of chromosome
      17. Aneurysmal bone cysts (ABCs) are rare, rapidly expanding, locally
      destructive, and often misdiagnosed lesions. Assessment of sacrum scalloping in
      NF-1 caused by aneurysmal bone cyst is described. CASE DESCRIPTION: A 15-year-old
      male was a patient with NF-1. He presented with cramping pain of the left soleus
      muscle, which had developed over the previous 3 months. The magnetic resonance
      imaging of the lumbar-sacrum region revealed a well-circumscribed multiloculated
      lesion located in the dorsal sacrum region and causing posterior vertebral
      scalloping and compression of nerve roots. The preoperative clinical suspicion
      was of a neurofibroma, a giant cell granuloma, or a lymphoma. However, the
      histopathologic diagnosis was consistent with ABC of the sacrum. This differed
      from our preoperative suspicion. CONCLUSION: The etiology of ABCs is still
      unknown. Some researchers have described ABCs with chromosomal abnormalities of
      16q22 and/or 17p13. This is consistent with NF-1, which develops through the
      inherited mutation of chromosome 17. Therefore, mutation of the chromosome may
      play an important role in the development of NF-1 and ABCs. Adequate diagnosis is
      necessary before treatment or biopsy of ABCs because bleeding may occur during
      operation or biopsy. Surgery is the treatment of choice for most ABCs. Adjuvant
      megavoltage radiotherapy is indicated for patients with recurrent tumors and
      whose tumors are inoperable.

PMID- 16427429
TI  - Fibrous dysplasia of the clivus with a second T8 bone lesion: case report.
AB  - BACKGROUND: We present a rare case of a probably poliostotic fibrous dysplasia of
      the clivus in a young woman with a clival and vertebral involvement. We also
      compare our case with data reported in tables that include all cases of clival
      fibrous dysplasia present in literature. CASE DESCRIPTION: Thirty-year-old women
      presented with headache. We reviewed radiological and clinical literature before
      surgery. It was possible to perform a preoperative diagnosis of fibrous dysplasia
      of the clivus so it was possible to adopt a minimally invasive surgical approach
      on the clivus. The diagnosis of fibrous dysplasia of the clivus was confirmed
      after the operation. As the patient was asymptomatic, we did not operate on the
      vertebral lesion which was stable after 1 year. CONCLUSION: We draw the
      conclusion that it is possible to obtain a correct preoperative diagnosis of
      fibrous dysplasia based on magnetic resonance imaging and computed tomographic
      scans; this makes it possible to avoid major surgical operations. The reported
      case is particularly interesting because apart from the clival fibrous dysplasia,
      a vertebral involvement of the same type can be assumed; this association has
      never been reported in literature.

PMID- 16427431
TI  - Direct access to the carotid circulation by cut down for endovascular neuro
      interventions.
AB  - BACKGROUND: Not all vascular lesions of the brain that are amenable to
      endovascular treatment are safely accessible via the transfemoral route. We
      describe our technique of carotid cut down for endovascular access and present a
      couple of illustrative cases. The increasing number of neurosurgeons performing
      endovascular procedures, or collaborating with interventional neuroradiologists,
      suggests that this technique should be revived. METHODS: Through a small
      transverse neck incision at the level of the thyroid cartilage, the CCA, ICA, and
      external carotid artery are exposed. After obtaining vascular control with vessel
      loupes, a purse-string suture is placed in the CCA. Puncture of the artery in the
      center of the purse string is followed by navigation of a wire, and then a
      sheath, into the ICA. The neurointervention is then carried out. At the
      conclusion of the procedure, the sheath is removed from the CCA and the purse
      string tied to secure the artery. RESULTS: This technique has allowed us to
      successfully access the intracranial circulation in 6 patients with challenging
      anatomy. We present here 2 of the original cases leading to our increasing use of
      this technique. CONCLUSION: Carotid cut down for direct puncture of the CCA is a
      viable option to gain access to the intracranial circulation when the
      transfemoral route seems difficult or dangerous.

PMID- 16427433
TI  - The future for neurology and psychiatry.

PMID- 16427434
TI  - Re: Ventricular catheter tack-down suture: technical note (Leuthardt EC, Chicoine
      R, Grubb RL. Surg Neurol 2005;64:270-1).

PMID- 16427436
TI  - The value of cranial computed tomography in high-risk, mildly head-injured
      patients.
AB  - BACKGROUND: The purpose of this article was to assess if high-risk, mildly head
      injured patients with normal CT scan present an outcome similar to the group with
      "low-risk MHI." METHODS: A total of 379 hospital charts of inpatients with
      Glasgow Coma Scale scores of 13, 14, and 15 were reviewed. Information regarding
      age, fGCS, trauma mechanism, cranial CT scan findings, hospital course, and
      follow-up using the GOS were obtained from all patients. RESULTS: Patients were
      separated in 3 groups: fGCS 13 (46 patients), fGCS 14 (138 patients), and fGCS 15
      (195 patients). The groups with different scores on fGCS did not differ regarding
      CT scan abnormalities, surgical treatment, or outcome. Patients were also
      separated in 2 groups based on CT scan findings: 266 patients had CT interpreted
      as abnormal and 113 had CT interpreted as normal. The 2 groups differed
      statistically regarding surgical treatment and scores on GOS (P < .05). There was
      no statistically significant difference between the 2 groups regarding sex,
      trauma mechanism, fGCS, or age. CONCLUSIONS: Our findings support the idea that a
      normal cranial CT scan in patients with fGCS scores of 13 or higher ascertain a
      low-risk MHI outcome and, therefore, such patients must be included in this
      category of traumatic brain injury. On the other hand, patients with cranial CT
      scan abnormalities should be included in the group with moderate head injury.

PMID- 16427437
TI  - Magnesium sulfate: role as possible attenuating factor in vasospasm morbidity.
AB  - BACKGROUND: Among the many complications of SAH, one of the most important is
      vasospasm. Several treatment alternatives have been proposed for this condition,
      with far-from-ideal results being obtained. Magnesium sulfate recently returned
      to the scene (with still unproven benefit) as an adjuvant in the treatment of
      vasospasm. METHODS: Seventy-two patients diagnosed with SAH by aneurysm rupture
      were submitted to microsurgery craniotomy and subdivided in 2 groups. Group 1,
      formed by 48 patients, received prophylactic hypervolemic and hemodilution
      therapy in addition to nimodipine. Group 2, composed of 24 patients, received the
      same treatment of group 1 with the addition of magnesium sulfate in continuous
      infusion from 120 to 150 mg a day, keeping serum magnesium levels close to double
      normal values. RESULTS: Age was 49 +/- 12.6 years. Ratio of female to male was
      3.16:1. Most patients were admitted in a Hunt-Hess grade 2 (46.4%) and Fisher
      grade 3 (52.8%). Anterior communicating artery aneurysms were the most common in
      location (38.8%). Both groups were compared, and there was no statistical
      difference related to age, sex, and Glasgow, Fisher, or Hunt-Hess admission
      grades. No statistical difference in vasospasm incidence was found between the
      two groups. However, in group 1, vasospasm was correlated with a longer
      hospitalization time (P = .0003), different from group 2, in which patients with
      vasospasm receiving magnesium sulfate required less hospitalization time.
      CONCLUSION: Magnesium did not seem to interfere in vasospasm frequency but
      apparently acted favorably in decreasing morbidity and length of hospital stay.

PMID- 16427438
TI  - Recent advances in the molecular genetics of malignant gliomas disclose targets
      for antitumor agent perillyl alcohol.
AB  - Tumors of glial origin such as glioblastoma multiforme (GBM) comprise the
      majority of human brain tumors. Despite advances in surgery, radiation, and
      chemotherapy, the prognosis for patients with malignant glioma has not improved,
      emphasizing the need for a search for new chemotherapeutic drugs. Deregulated p21
      Ras function, as a result of mutation, overexpression, or growth factor-induced
      overactivation, contributes to the growth of GBM. The monoterpene perillyl
      alcohol (POH) has preventive and therapeutic effects in a wide variety of
      preclinical tumor models and is currently under phase I and phase II clinical
      trials. As inhibition of posttranslational isoprenylation of Ras, a family of
      proteins that are involved in signal transduction is among the drug-related
      activities observed in this compound; POH may be a potential chemotherapeutic
      agent for GBM. Intranasal delivery is a practical and noninvasive approach that
      allows therapeutic agents that do not cross the blood-brain barrier to enter the
      central nervous system, reducing unwanted systemic side effects. This article
      describes the effect of intranasal delivery of POH in a patient with relapsed
      GBM.

PMID- 16427442
TI  - Early surgical treatment of nonsyndromic craniosynostosis.
AB  - BACKGROUND: Craniosynostosis, a premature fusion of cranial sutures, can happen
      as an isolated defect (nonsyndromic) or as part of a syndrome. It may lead to
      raised intracranial pressure and deformity of both the cranial and facial
      skeletons. Early surgery is usually the best treatment choice. The aim of this
      study was to review the experience of a multidisciplinary staff with the surgical
      treatment of nonsyndromic craniosynostosis. METHODS: All the nonsyndromic
      craniosynostosis cases treated surgically from 1991 to 2005 at 2 neurosurgical
      centers were reviewed. The variables analyzed were sex, age, weight, type of
      deformity, estimated volemia, surgical technique, surgical time, blood loss, PO
      hospitalization time, and complications. All data were stored in a database and
      analyzed with Microsoft Access (Microsoft Corp, Seattle, WA) and SPSS V11.0
      (SPSS, Inc, Chicago, IL). RESULTS: The sample consisted of 120 patients (70
      males, 50 females). Six patients were excluded because of their atypical timing
      of treatment (average age, 72 months). The final average age was 7.08 months
      (variation, 1-18), and the average weight was 7.8 kg. The types of deformities
      found were scaphocephaly (n = 54, 45%), plagiocephaly (n = 27, 22%),
      trigonocephaly (n = 19, 16%), brachycephaly (n = 16, 13%), and oxycephaly (n = 4,
      3%). The mean surgical time was 186 minutes and the mean PO hospitalization time
      was 6.8 days. The mortality on this series was 2.6% (3 patients). In the last
      operated cases, a significant improvement in morbid-mortality was observed.
      CONCLUSION: A multidisciplinary approach, including neurosurgeons, neurologists,
      and pediatricians, and appropriate training of the clinical surgical staff can
      minimize the risks and decrease the complications in the treatment of
      craniosynostosis, leading to a satisfactory outcome.

PMID- 16427444
TI  - Stereotactic computed tomography-guided brain biopsy: diagnostic yield based on a
      series of 170 patients.
AB  - BACKGROUND: Stereotactic CT-guided biopsy is a valuable and safe procedure for
      diagnosing intracranial lesions. The objectives of this article are to analyze
      the diagnostic yield in a series of stereotactic CT-guided brain biopsies and to
      evaluate whether predictive factors may influence diagnostic yield. METHODS: The
      medical records of a series of patients who underwent stereotactic CT-guided
      brain biopsy from 1993 to 2005 in a neurosurgical center were reviewed. Clinical
      data were stored and analyzed with Microsoft Access (Microsoft Corp, Seattle, WA)
      and SPSS V11.0 software (SPSS, Inc, Chicago, IL). The following variables were
      analyzed: age, sex, anatomopathologic diagnosis, lesion topography and volume,
      postsurgical complications, and predictive factors that may affect diagnostic
      yield. RESULTS: One hundred seventy patients (102 males, 68 females; average age,
      48.5 years) were analyzed. Stereotactic CT-guided biopsies allowed diagnosis in
      157 cases (92%). The most frequent anatomopathologic diagnoses were high-grade
      glioma (n = 45), low-grade glioma (n = 31), nonspecific inflammatory lesions (n =
      19), metastasis (n = 10), and lymphoma (n = 10). The most frequent topographies
      were frontal (n = 42), basal ganglia (n = 40), and parietal (n = 27) and front
      parietal lobes (n = 9). Complications occurred in 5 patients (2.9%). Mortality
      rate was 1.2% (2 patients). Age had a positive impact, whereas female sex
      negatively affected diagnostic yield. All other predictive factors analyzed were
      not significant. CONCLUSION: Stereotactic CT-guided brain biopsies performed
      presented acceptable anatomopathologic diagnostic rate. Age had a positive
      impact, whereas female sex negatively affected diagnostic yield in this series.

PMID- 16427449
TI  - Stay tuned.

PMID- 16427445
TI  - Transbasal approach to skull base tumors: evaluation and proposal of
      classification.
AB  - A clinical study of the TBA was performed in 22 patients harboring tumors of the
      skull base. The follow-up ranged from 3 to 89 months (average, 30.5 months). The
      main complications were intracerebral hematoma, ptosis, and infection. One
      patient died (4.5%) because of an extradural hematoma. Eight patients died during
      the follow-up because of tumor complications. Among the survivals, the median of
      the Karnofsky index was 96.4. Based on this study, we propose a classification
      for the TBA, according to its extension.

PMID- 16427450
TI  - Resilon will biodegrade from lipases released by bacteria or by bacterial or
      salivary enzymes.

PMID- 16427452
TI  - A Cochrane systematic review finds no evidence to support the use of antibiotics
      for pain relief in irreversible pulpitis.
AB  - The Cochrane Systematic Review promotes evidence-based outcomes studies. The
      review summarized here was conducted in an attempt to achieve reliable evidence
      concerning the effectiveness, or otherwise, of prescribing antibiotics for
      patients having irreversible pulpitis. A competent search strategy was developed
      and used across several databases including MEDLINE to identify randomized
      controlled trials for inclusion. Assessment of methodological quality was based
      on criteria defined by The Cochrane Collaboration. Clinical outcome, expressed in
      terms of pain relief, was examined. There was a relative dearth of research
      providing a high level of evidence. Only one methodologically sound trial was
      found that compared pain relief with systemic antibiotic/analgesic treatment
      against a placebo/analgesic combination during the acute preoperative phase of
      irreversible pulpitis. Although the selected study used a relatively small, low
      powered sample, it did provide some evidence that there is no significant
      difference in pain relief for patients with untreated irreversible pulpitis who
      received antibiotics versus those who did not. These findings increase the
      rationale to investigate the teaching of safe and effective antibiotic
      prescribing in endodontics and to advance the development of appropriate evidence
      based clinical guidelines.

PMID- 16427454
TI  - Pulpal inflammation and incidence of coronary heart disease.
AB  - Pulpal inflammation is primarily caused by coronal caries, and leads to root
      canal therapy (RCT). Chronic inflammation has been associated with various
      cardiovascular diseases. This study evaluates the association between pulpal
      inflammation (using RCT as a surrogate) and incident coronary heart disease
      (CHD). We report results among males from the Health Professionals Follow-Up
      Study (HPFS), excluding participants with prior cardiovascular disease or
      diabetes. We obtained RCT data from the HPFS cohort (n = 34,683). Compared to men
      without RCT, those with >/=1 RCT had a multivariate RR of 1.21 (95% CI 1.05-1.40)
      for CHD. The association was limited to dentists (RR = 1.38; 95% CI 1.14-1.67).
      There was no association among nondentists (RR = 1.03). Dental caries was not
      associated with CHD. The results suggest a possible modest association between
      pulpal inflammation and CHD.

PMID- 16427453
TI  - Enterococcus faecalis: its role in root canal treatment failure and current
      concepts in retreatment.
AB  - Enterococcus faecalis is a microorganism commonly detected in asymptomatic,
      persistent endodontic infections. Its prevalence in such infections ranges from
      24% to 77%. This finding can be explained by various survival and virulence
      factors possessed by E. faecalis, including its ability to compete with other
      microorganisms, invade dentinal tubules, and resist nutritional deprivation. Use
      of good aseptic technique, increased apical preparation sizes, and inclusion of
      2% chlorhexidine in combination with sodium hypochlorite are currently the most
      effective methods to combat E. faecalis within the root canal systems of teeth.
      In the changing face of dental care, continued research on E. faecalis and its
      elimination from the dental apparatus may well define the future of the
      endodontic specialty.

PMID- 16427455
TI  - Prevalence of Enterococcus faecalis at multiple oral sites in endodontic patients
      using culture and PCR.
AB  - There are conflicting data on the occurrence of Enterococcus faecalis in the oral
      cavity of endodontic patients. This study investigated the prevalence of E.
      faecalis in multi-site oral samples (n = 136) from 41 endodontic patients using
      culture and polymerase chain reaction (PCR). Additionally, culturable strains
      were investigated for virulence traits. Overall, E. faecalis was detected in at
      least one tongue, oral rinse, or gingival sulcus sample in 68% of patients and in
      the root canals only in 5% of patients. In 21 patients from whom samples were
      obtained from all four sites, E. faecalis was detected in more tongue than
      gingival sulcus, oral rinse, and root canal samples (43, 14, 10, and 10%,
      respectively; p = 0.0148, chi(2)), and in proportionally greater numbers of
      patients with gingivitis/periodontitis compared to healthy periodontium (73%
      versus 20%; p = 0.03, Fisher's exact test). PCR was more sensitive than culture
      in detecting E. faecalis in oral samples (32% and 4%, respectively; p < 0.0001,
      McNemar's test). Multiple virulence traits were identified in culturable strains.

PMID- 16427457
TI  - Influence of orthodontic dental movement on the healing process of teeth with
      periapical lesions.
AB  - The purpose of this study was to histomorphologically evaluate (in dog's teeth)
      the influence of tooth movement in the healing of chronic periapical lesions.
      Thirty roots of incisors and premolars of two dogs (1-year-old) were used in this
      research. After pulpectomy, the root canals remained exposed to the oral
      environment for 6 months for achievement of periapical lesions. Twenty root
      canals were biomechanically prepared and received a calcium hydroxide dressing
      for 14 days before being filled with gutta-percha points and Sealapex sealer.
      After root canal treatment, some incisors were submitted to orthodontic movement,
      whereas the other roots remained without orthodontic movement. The orthodontic
      appliance was removed at 5 months and 15 days after treatment, the dogs were
      killed 15 days later and the specimens were prepared for histomorphological
      analysis. The results showed that the orthodontic movement delayed, but did not
      hinder, the periapical healing process.

PMID- 16427456
TI  - Multiplex polymerase chain reaction detection of black-pigmented bacteria in
      infections of endodontic origin.
AB  - The purpose of this study was to detect the presence of Porphyromonas
      endodontalis, P. gingivalis, Prevotella intermedia, P. nigrescens, and P.
      tannerae from clinical samples using multiplex polymerase chain reactions (PCR).
      Two different multiplex PCR protocols were used (one for the two Porphyromonas
      species and the other for the three Prevotella species), each one using a primer
      pair specific for each target species. The results were compared to those of the
      conventional culture procedures. Microbial samples were taken aseptically from 40
      infected root canals and abscesses from patients. Samples were cultured in an
      anaerobic condition for conventional identification using a Rapid ID 32 A kit.
      Multiplex PCR was processed using the DNA extracted from each sample. At least
      one of the five species of black-pigmented bacteria (BPB) were detected in 65%
      (26 of 40) of the samples using multiplex PCR, and in 15% (6 of 40) using the
      conventional culture procedures. Multiplex PCR was more rapid, sensitive,
      specific, and effective in detecting BPB than the conventional culture
      procedures.

PMID- 16427458
TI  - Effects of an intracanal glass ionomer barrier on coronal microleakage in teeth
      with post space.
AB  - Bacterial microleakage of the remaining gutta-percha in teeth prepared for post
      space with and without the use of an intracanal glass ionomer barrier was
      evaluated. Forty distal roots of mandibular molars were instrumented, obturated
      with gutta-percha and AH Plus sealer, and post spaces created. Teeth were divided
      as follows: Group I, 3 mm of gutta-percha; group II, 4 mm of gutta-percha; group
      III, 2 mm of gutta-percha plus 1 mm of Vitrebond; and group IV, 3 mm gutta-percha
      plus 1 mm Vitrebond. The roots were suspended in Rogosa SL broth and Lactobacilli
      casei was used as a microbial marker. At the end of 92 days, the mean number of
      days for the broth to turn turbid was group I, 23.8; group II, 43.0; group III,
      57.4, and group IV, 70.5. A two-way ANOVA showed differences between the groups
      and a post hoc Tukey HSD analysis revealed the following significant differences
      (p < 0.05): Group I leaked faster than groups III and IV and group II leaked
      faster than group IV. In clinical situations of teeth with compromised crown-root
      ratio that require a post and core, 1 mm of Vitrebond over 2 or 3 mm remaining
      gutta-percha could reduce the risk of recontamination of the apical gutta-percha.

PMID- 16427459
TI  - Penetration depth of warm vertical Gutta-Percha pluggers: impact of apical
      preparation.
AB  - The warm vertical gutta-percha compaction technique requires canals to be
      sufficiently flared to allow the tip of the plugger to penetrate to the apical
      third. The aim of the present study was to determine whether apical preparation
      or finishing instruments could be used to improve the penetration depth of
      pluggers. Single-root canals (48) were prepared using different rotary Ni-Ti
      instruments: M File System (I), ProTaper (II), HEROShaper (III), and EndoK3 (IV).
      Finger and heat (Endotwinn) pluggers were introduced into the canals, one after
      the other, and their penetration depths were measured. The apical thirds of the
      canals were then flared with specific instrumentation and the penetration depths
      of the pluggers were once again measured. After the initial preparation, the
      smallest diameter pluggers (No. 1 and F) could be inserted 5 to 7 mm short of
      working length without difficulty. Apical flaring improved the maximum
      penetration depth of the finger plugger by 1.76 mm and the heat plugger by 1.52
      mm The deepest penetration was obtained with the EndoK3, ProTaper, and HEROShaper
      instruments. By accentuating the taper, apical flaring facilitated the
      penetration of warm vertical gutta-percha compaction pluggers.

PMID- 16427460
TI  - Bacterial leakage in roots filled with different medicaments and sealed with
      Cavit.
AB  - The aim of this study was to evaluate the time required by four different root
      canal medications coupled with the temporary filling material Cavit (ESPE,
      Seefeld, Germany) to prevent penetration of bacteria into the root canal. There
      were 145 roots prepared in a standardized manner. Four groups with 15 samples
      each were dressed with calcium hydroxide (Ca(OH)(2)), a 5% chlorhexidine gel
      (CHX), a chloromono-campherphenolic compound (ChKM), and Ledermix (LM),
      respectively, and sealed with Cavit. Four control groups contained identical
      medications but the roots were left unsealed. The 25 remaining roots served as
      additional controls. A standard setup for bacterial leakage studies was chosen
      with Staphylococcus epidermidis as test strain. Cavit application resulted in a
      significantly better seal compared with the unsealed groups. In the Cavit-sealed
      groups, all groups differed significantly from one another except for the CHX and
      the ChKM groups. The Ca(OH)(2) medicated roots provided the longest protection
      (median of 36 days), followed by the Ledermix-group (27 days) and the CHX (18
      days) or ChKM groups (19 days). It may be concluded that Cavit-sealed and
      medicated root canals do not provide adequate protection against bacterial
      leakage for more than 1 month.

PMID- 16427461
TI  - Setting times of Resilon and other sealers in aerobic and anaerobic environments.
AB  - Eleven sealers, including Resilon sealer, were mixed according to manufacturer's
      instructions. Setting times were determined in both aerobic and anaerobic
      environments. Two samples of each sealer were mixed and placed in the following
      conditions: (a) uncovered in an aerobic incubator; (b) covered with a glass cover
      slip in the aerobic incubator; (c) covered with phosphate buffered saline in an
      aerobic incubator; (d) uncovered in an anaerobic incubator; (e) light cured and
      then placed in the aerobic incubator (Resilon only). All samples were tested for
      setting times with a Gillmore needle at 15, 30, and 60 minutes, then hourly up to
      8 hours, then at 24, 48, and 72 hours, and then weekly up to 3 weeks. Ketac Endo
      and Kerr Tubliseal, were the fastest sealers to set in aerobic environments.
      Ketac Endo and Resilon were the fastest sealers to set in anaerobic environments.
      Roth 801 and Roth 811 were the slowest sealers to set, taking over 3 weeks to set
      in either anaerobic or aerobic environments. Resilon sealer set in 30 minutes in
      both anaerobic environments. However, in the presence of air, Resilon took a week
      to set and when placed in PBS, an uncured layer remained on the surface.

PMID- 16427462
TI  - Bondability of Resilon to a methacrylate-based root canal sealer.
AB  - Resilon broadens the dimensions of endodontic adhesion by introducing the
      possibility of creating monoblocs between root canal filling materials and
      intraradicular dentin by using methacrylate-based sealers. The adhesive strength
      of Resilon to RealSeal, a methacrylate-based root canal sealer, was evaluated
      using a modified microshear bond testing design. Flat Resilon surfaces with
      different roughness were created for bonding to the sealer and compared to a
      composite control. The composite control exhibited mean shear strength 7.3 to
      26.9 times higher than those of the Resilon groups. Shear strength differences
      among the Resilon groups of different surface roughness highlighted the
      contribution of micromechanical versus chemical coupling in sealer retention.
      Ultrastructural evidence of phase separation of polymeric components in Resilon
      suggested that the amount of dimethacrylate incorporated into this filled,
      thermoplastic composite may not yet be optimized for effective chemical coupling
      to methacrylate-based sealers.

PMID- 16427463
TI  - Killing of Enterococcus faecalis by MTAD and chlorhexidine digluconate with or
      without cetrimide in the presence or absence of dentine powder or BSA.
AB  - The antibacterial efficacy of irrigating solutions and local disinfectants used
      in endodontics appears poorer in vivo than in vitro. One explanation may be
      inactivation by compounds present in the root canal. MTAD (a mixture of
      tetracycline isomer, acid, and detergent) is a new root canal irrigation solution
      with antibacterial activity. The aim of this study was to investigate the
      antibacterial activity of MTAD and chlorhexidine towards two strains of
      Enterococcus faecalis and the inhibitory effects of dentine and bovine serum
      albumin on the antibacterial activity. Survival of bacteria exposed to the
      medicaments in the presence or absence of inhibitors was monitored in an in vitro
      model. Full concentration (100%) MTAD and 0.2% chlorhexidine rapidly killed both
      strains. Combining chlorhexidine with cetrimide further reduced the time required
      for killing. The presence of dentine or BSA caused a marked delay in killing by
      both medicaments. The two E. faecalis strains tested showed minor differences in
      their susceptibility to the disinfectants.

PMID- 16427464
TI  - Accuracy of root length determination using Tri Auto ZX and ProTaper instruments:
      an in vitro study.
AB  - The accuracy of the electronic apex locator feature of Tri Auto ZX was assessed.
      Twenty distobuccal roots were selected and, after endodontic access, placed in
      plastic cylinders filled with 2% agar until completely covered. The roots were
      divided in two groups according to the calibration of the automatic apical
      reverse mechanism of Tri Auto ZX, at 1 and 2 mm from the apical foramen.
      Preparation was performed with ProTaper instruments connected to the device.
      Afterwards, the last file used was introduced into the canal and fixed in place
      with acrylic resin. The roots were removed from the agar and ground until
      exposure of the file. The distances between file tip and apical foramen were
      submitted to statistical analysis. The distances reached were actually shorter
      than the preset distances in every case, however, they were considered clinically
      acceptable. Setting the reverse mechanism at 1 mm was more reliable than at 2 mm.

PMID- 16427465
TI  - In vitro evaluation of the antimicrobial effects of a root canal sealer
      antibiotic combination against Enterococcus faecalis.
AB  - The purpose of this in vitro study was to evaluate the antimicrobial effects of
      five antibiotics when added to Kerr Pulp Canal Sealer EWT against Enterococcus
      faecalis. Five antibiotics: amoxicillin, penicillin, clindamycin, metronidazole,
      and doxycycline, were added separately to Kerr sealer. Thirty brain heart
      infusion agar plates were inoculated with E. faecalis and sterile paper discs
      containing a sealer-antibiotic combination were randomly assigned to the
      inoculated plates. Kerr sealer on a sterile paper disc and a blank sterile paper
      disc served as the controls. Fifteen plates were incubated aerobically and the
      remaining 15 plates were incubated anaerobically at 37 degrees C. The zones of
      inhibition were measured at 48 hours. No significant differences (p > 0.05) were
      found between aerobic and anaerobic groups. The groups were combined and data
      analysis using a one-way ANOVA and Tukey's post hoc test was performed. Results
      revealed that sealer-antibiotic combinations containing amoxicillin, penicillin,
      clindamycin, and doxycycline had a significant difference (p < 0.001) in the mean
      zones of inhibition when compared to Kerr EWT sealer alone. No significant
      differences (p > 0.05) were found between the metronidazole-sealer combinations
      and Kerr EWT sealer alone.

PMID- 16427466
TI  - Antimicrobial efficacy of medicated root canal filling materials.
AB  - Bacteria remaining within the root canal system are a significant factor in
      endodontic failures. The aim of this in vitro study was to evaluate the
      antimicrobial efficacy of commercially available gutta-percha formulations
      against common endodontic pathogens. Standard, tetracycline, or iodoform (also
      called medicated gutta-percha; MGP) containing gutta-percha were tested against
      Actinomyces israelii, A. naeslundii, Enterococcus faecalis, and Fusobacterium
      nucleatum using the agar diffusion method. Resilon points and tetracycline
      disks/E-tests were used as negative and positive controls, respectively. Resilon
      did not display antimicrobial properties. Standard gutta-percha and MGP inhibited
      F. nucleatum and A. naeslundii, with MGP also inhibiting A. israelii.
      Tetracycline containing gutta-percha was found to inhibit growth from all four
      bacterial species tested. The results of this study suggest that the use of
      tetracycline containing gutta-percha as an obturation material may be useful as a
      complement to the cleaning and disinfection phase of root canal procedures.

PMID- 16427467
TI  - Peripheral ameloblastoma: a case report and review of the literature.
AB  - Peripheral ameloblastoma is a rare, benign odontogenic tumor that histologically
      resembles an intraosseous ameloblastoma but develops in the soft tissues of the
      gingiva and mucosa and exhibits an innocuous clinical behavior. We report a case
      of a recurrent peripheral ameloblastoma in a 61-year-old man that presented as a
      painless swelling on the maxillary anterior labial attached gingiva. Clinical and
      histopathologic features of this lesion are discussed. The peripheral
      ameloblastoma should be included in the differential diagnosis of a gingival
      lesion clinically resembling any of the myriads of entities seen on the gingiva
      including a pyogenic granuloma, peripheral giant cell granuloma, or
      parulis/gumboil. We believe this case highlights the need for submitting excised
      tissue for microscopic examination.

PMID- 16427468
TI  - Monitoring diabetes treatment in New York City.

PMID- 16427469
TI  - Global avian influenza controls must be scaled up now.

PMID- 16427470
TI  - New hope for a complete smoking ban in public places.

PMID- 16427471
TI  - Missing female births in India.

PMID- 16427472
TI  - Prevention and treatment of postherpetic neuralgia.

PMID- 16427473
TI  - The health of nations: happy birthday WTO.

PMID- 16427474
TI  - Better health statistics are possible.

PMID- 16427475
TI  - Is cannabis use psychotogenic?

PMID- 16427476
TI  - Non-steroidal anti-inflammatory drugs and urinary retention.

PMID- 16427477
TI  - Expression of concern: non-steroidal anti-inflammatory drugs and the risk of oral
      cancer.

PMID- 16427479
TI  - Melissa Brown.

PMID- 16427480
TI  - ASCOT-BPLA.

PMID- 16427481
TI  - ASCOT-BPLA.

PMID- 16427482
TI  - ASCOT-BPLA.

PMID- 16427483
TI  - ASCOT-BPLA.

PMID- 16427485
TI  - Beta blockers for the treatment of primary hypertension.

PMID- 16427486
TI  - Beta blockers for the treatment of primary hypertension.

PMID- 16427487
TI  - Beta blockers for the treatment of primary hypertension.

PMID- 16427489
TI  - Low female[corrected]-to-male [corrected] sex ratio of children born in India:
      national survey of 1.1 million households.
AB  - BACKGROUND: Fewer girls than boys are born in India. Various hypotheses have been
      proposed to explain this low sex ratio. Our aim was to ascertain the contribution
      of prenatal sex determination and selective abortion as measured by previous
      birth sex. METHODS: We analysed data obtained for the Special Fertility and
      Mortality Survey undertaken in 1998. Ever-married women living in 1.1 million
      households in 6671 nationally-representative units were asked questions about
      their fertility history and children born in 1997. FINDINGS: For the 133 738
      births studied for 1997, the adjusted sex ratio for the second birth when the
      preceding child was a girl was 759 per 1000 males (99% CI 731-787). The adjusted
      sex ratio for the third child was 719 (675-762) if the previous two children were
      girls. By contrast, adjusted sex ratios for second or third births if the
      previous children were boys were about equal (1102 and 1176, respectively).
      Mothers with grade 10 or higher education had a significantly lower adjusted sex
      ratio (683, 610-756) than did illiterate mothers (869, 820-917). Stillbirths and
      neonatal deaths were more commonly male, and the numbers of stillbirths were
      fewer than the numbers of missing births, suggesting that female infanticide does
      not account for the difference. INTERPRETATION: Prenatal sex determination
      followed by selective abortion of female fetuses is the most plausible
      explanation for the low sex ratio at birth in India. Women most clearly at risk
      are those who already have one or two female children. Based on conservative
      assumptions, the practice accounts for about 0.5 million missing female births
      yearly, translating over the past 2 decades into the abortion of some 10 million
      female fetuses.

PMID- 16427490
TI  - The PINE study of epidural steroids and local anaesthetics to prevent
      postherpetic neuralgia: a randomised controlled trial.
AB  - BACKGROUND: Postherpetic neuralgia is the most frequent complication of herpes
      zoster. Treatment of this neuropathic pain syndrome is difficult and often
      disappointing. We assessed the effectiveness of a single epidural injection of
      steroids and local anaesthetics for prevention of postherpetic neuralgia in older
      patients with herpes zoster. METHODS: We randomly assigned 598 patients older
      than 50 years, with acute herpes zoster (rash <7 days) below dermatome C6, to
      receive either standard therapy (oral antivirals and analgesics) or standard
      therapy with one additional epidural injection of 80 mg methylprednisolone
      acetate and 10 mg bupivacaine. The primary endpoint was the proportion of
      patients with zoster-associated pain 1 month after inclusion. Analyses were by
      intention-to-treat. This study is registered as an International Standard
      Randomised Controlled Trial, number ISRCTN32866390. FINDINGS: At 1 month, 137
      (48%) patients in the epidural group reported pain compared with 164 (58%) in the
      control group (relative risk [RR] 0.83, 95% CI 0.71-0.97, p=0.02). After 3 months
      these values were 58 (21%) and 63 (24%) respectively (0.89, 0.65-1.21, p=0.47)
      and, at 6 months, 39 (15%) and 44 (17%; 0.85, 0.57-1.13, p=0.43). We detected no
      subgroups in which the relative risk for pain 1 month after inclusion
      substantially differed from the overall estimate. No patient had major adverse
      events related to epidural injection. INTERPRETATION: A single epidural injection
      of steroids and local anaesthetics in the acute phase of herpes zoster has a
      modest effect in reducing zoster-associated pain for 1 month. This treatment is
      not effective for prevention of long-term postherpetic neuralgia.

PMID- 16427491
TI  - 3-month and 12-month mortality after first liver transplant in adults in Europe:
      predictive models for outcome.
AB  - BACKGROUND: Mortality after liver transplantation depends on heterogeneous
      recipient and donor factors. Our aim was to assess risk of death and to develop
      models to help predict mortality after liver transplantation. METHODS: We
      analysed data from 34,664 first adult liver transplants from the European Liver
      Transplant Registry to identify factors associated with mortality at 3-months
      (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after
      transplantation. We used multivariable logistic regression models to generate
      mortality scores for each individual, and assessed model discrimination and
      calibration on an independent validation dataset (n=9489 for 3-month model and
      n=8313 for 12-month model). FINDINGS: 2540 of 21,605 (12%) individuals in the 3
      month training sample had died by 3 months. Compared with those transplanted in
      2000-03, those transplanted earlier had a higher risk of death. Increased
      mortality at 3-months post-transplantation was associated with acute liver
      failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16),
      compatible (1.22) or incompatible (2.07) donor-recipient blood group, older
      recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia
      time of longer than 13 h (1.38), and low United Network for Organ Sharing score
      (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma,
      alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years
      or younger, or less, hepatitis B, and larger size of transplant centre (> or = 70
      transplants per year) were associated with improved early outcomes. The 3-month
      mortality score discriminated well between those who did and did not die in the
      validation sample (C statistic=0.688). We noted similar findings for 12-month
      mortality, although deaths were generally underestimated at this timepoint.
      INTERPRETATION: The 3-month and 12-month mortality models can be effectively used
      to assess outcomes both within and between centres. Furthermore, the models
      provide a means of assessing the risk of post-transplantation mortality, giving
      clinicians important data on which to base strategic decisions about transplant
      policy in particular individuals or groups.

PMID- 16427492
TI  - Lymphoproliferative disorders after paediatric heart transplantation: a multi
      institutional study.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are an important
      cause of morbidity and mortality after organ transplantation. We sought to better
      define the prevalence, pathology, current therapeutic approaches, and outcomes of
      PTLD in a large group of children who had received heart transplants. METHODS: We
      assessed data on patients followed up at 19 centres in the Pediatric Heart
      Transplant Study (PHTS) from 1993 to 2002. Probability of freedom from PTLD was
      assessed along with details of presentation, pathology, treatment, and outcomes.
      Risk factors for survival and event-free survival were investigated. FINDINGS: Of
      1184 primary transplant recipients, 56 (5%) developed PTLD. Probability of
      freedom from PTLD was 98% at 1 year, 94% at 3 years, and 92% at 5 years. Mean
      time to PTLD was 23.8 months. Most common sites of disease were gastrointestinal
      tract (n=22, 39%) and respiratory system (n=14, 25%). Histology was polymorphic
      in 35 (65%) and monomorphic in 19 (35%). 47 of 48 cases were of B-cell origin, 39
      of 45 (87%) were Epstein-Barr virus positive. Probability of survival was 75% at
      1 year, 68% at 3 years, and 67% at 5 years after diagnosis. Death from graft loss
      was as frequent as death from PTLD. INTERPRETATION: About 5% of paediatric heart
      transplant recipients develop PTLD, almost always of B-cell lineage and driven by
      Epstein-Barr virus. Although many achieve satisfactory outcomes, mortality
      remains substantial with death due to progressive disease and allograft loss.
      Advances in management should focus on strategies to protect the allograft as
      well as improved therapies for PTLD.

PMID- 16427493
TI  - A pain in the back.

PMID- 16427494
TI  - Retroperitoneal fibrosis.
AB  - Retroperitoneal fibrosis encompasses a range of diseases characterised by the
      presence of a fibro-inflammatory tissue, which usually surrounds the abdominal
      aorta and the iliac arteries and extends into the retroperitoneum to envelop
      neighbouring structures--eg, ureters. Retroperitoneal fibrosis is generally
      idiopathic, but can also be secondary to the use of certain drugs, malignant
      diseases, infections, and surgery. Idiopathic disease was thought to result from
      a local inflammatory reaction to antigens in the atherosclerotic plaques of the
      abdominal aorta, but clinicolaboratory findings--namely, the presence of
      constitutional symptoms and the high concentrations of acute-phase reactants--and
      the frequent association of the disease with autoimmune diseases that involve
      other organs suggest that it might be a manifestation of a systemic autoimmune or
      inflammatory disease. Steroids are normally used to treat idiopathic
      retroperitoneal fibrosis, although other options--eg, immunosuppressants,
      tamoxifen--are available. The outlook is usually good, but, if not appropriately
      diagnosed or treated, the disease can cause severe complications, such as end
      stage renal failure. Here, we review the different aspects of retroperitoneal
      fibrosis, focusing on idiopathic retroperitoneal fibrosis and on the differential
      diagnosis associated with the secondary forms.

PMID- 16427495
TI  - Clinical perspectives of emerging pathogens in bleeding disorders.
AB  - As a result of immunological and nucleic-acid screening of plasma donations for
      transfusion-transmissible viruses, and the incorporation of viral reduction
      processes during plasma fractionation, coagulation-factor concentrates (CFC) are
      now judged safe in terms of many known infectious agents, including hepatitis B
      and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging
      pathogens could pose future threats, particularly those with blood-borne stages
      that are resistant to viral-inactivation steps in the manufacturing process, such
      as non-lipid-coated viruses. As outlined in this Review, better understanding of
      infectious diseases allows challenges from newly described agents of potential
      concern in the future to be anticipated, but the processes of zoonotic
      transmission and genetic selection or modification ensure that plasma-derived
      products will continue to be subject to infectious concerns. Manufacturers of
      plasma-derived CFC have addressed the issue of emerging infectious agents by
      developing recombinant products that limit the need for human plasma during
      production. Such recombinant products have extended the safety profile of their
      predecessors by ensuring that all reagents used for cell culture, purification
      steps, and stabilisation and storage buffers are completely independent of human
      plasma.

PMID- 16427496
TI  - Controversies in atrial fibrillation.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia, and
      contributes greatly to cardiovascular morbidity and mortality. Many aspects of
      the management of atrial fibrillation remain controversial. We address nine
      specific controversies in atrial fibrillation management, briefly focusing on the
      relations between mechanisms and therapy, the roles of rhythm and rate control,
      the definition of optimum rate control, the need for early cardioversion to
      prevent remodelling, the comparison of electrical with pharmacological
      cardioversion, the selection of patients for long-term oral anticoagulation, the
      roles of novel long-term anticoagulation approaches and ablation therapy, and the
      potential usefulness of upstream therapy targeting substrate development. The
      background of every controversy is reviewed and our opinions expressed. Here, we
      hope to inform physicians about the most important controversies in this
      specialty and stimulate investigators to address unresolved issues.

PMID- 16427497
TI  - The patient whose hypocalcaemia worsened after prompt intravenous calcium
      replacement therapy.

PMID- 16427498
TI  - Charcot neuroarthropathy in the era of HAART.

PMID- 16427500
TI  - LASER-tissue interactions.
AB  - As new laser devices continue to emerge, it becomes increasingly important for
      the clinical dermatologist to understand the basic principles behind their
      operation. A fundamental understanding of how lasers interact with tissue will
      enable the physician to choose the most appropriate laser for a given clinical
      situation. Although the physical laws guiding laser design are vastly complex,
      the fundamental principles of laser-tissue interaction can be summarized as they
      are applicable to the clinician.

PMID- 16427501
TI  - Laser treatment of vascular lesions.
AB  - Laser treatment of vascular lesions remains one of the more common applications
      of lasers in dermatology. In fact, lasers have largely become the treatment of
      choice for vascular birthmarks such as hemangiomas and port-wine stains and the
      definitive treatment of the telangiectatic form of rosacea. The range of
      congenital and acquired vascular lesions effectively treated with lasers
      continues to expand.

PMID- 16427502
TI  - Laser-mediated photodynamic therapy.
AB  - Photodynamic therapy (PDT) has evolved since its inception at the beginning of
      the 20th century, when it was defined as an oxygen-dependent reaction between a
      photosensitizing dye and light. Photosensitizers and light sources have since
      been continually optimized for distinct applications and tissues. Systemic
      porphyrins, such as hematoporphyrin, were the first photosensitizers to be used,
      mostly to treat tumors. The first light sources used were broad-band, noncoherent
      lights, such as quartz, xenon, tungsten, or halogen lamps. The wavelengths of
      light chosen were based upon the absorption spectrum of porphyrins: blue because
      the largest peak is at 400 nm (the Soret band) and red because of its greater
      penetration depth but lesser absorption at 650 nm (a Q band). Systemic
      photosensitizers caused prolonged photosensitivity, and broad-band light sources
      had limitations and side effects. The development of topical photosensitizers,
      such as 5-aminolevulinic acid, and the advent of lasers in recent years have
      advanced PDT for cutaneous use. In the 1990s, red lasers were applied to PDT
      because of their increased skin penetration despite lesser absorption by
      porphyrins. Broad-band blue light and red light have been studied extensively,
      the former achieving Food and Drug Administration approval in combination with
      topical aminolevulinic acid for the treatment of actinic keratosis in 1997. These
      lasers and light sources caused significant side effects, such as discomfort,
      erythema, crusting, blistering, and dyspigmentation. The recent application of
      the long-pulsed pulsed dye laser (595 nm) after topical aminolevulinic acid
      greatly minimized side effects without compromising efficacy. Long-pulsed pulsed
      dye laser-mediated PDT has since been shown to be effective in treatment of
      actinic keratosis, actinic cheilitis, sebaceous hyperplasia, lichen sclerosus,
      and, most recently, acne vulgaris. Finally, intense pulsed light sources have
      been introduced to PDT for the treatment of photodamage and acne, offering
      advantages of versatility in wavelengths and applications.

PMID- 16427503
TI  - Laser therapy for acne.
AB  - Considered the most common skin disorder, acne affects millions of people every
      year. This multifactorial condition of the pilosebaceous follicle is a
      combination of at least four different primary pathogeneses. In recent years,
      acne therapies have been improving, becoming more effective, and targeting one or
      more of these causes. Many current therapies have drawbacks involving patient
      compliance, systemic toxicities, and bacterial resistance. Lasers are now
      established options in the armamentarium to treat acne. The 532-nm potassium
      titanyl phosphate laser, 585- and 595-nm pulsed dye lasers, 1450-nm diode laser,
      and 1540-nm erbium glass laser have been used with variable efficacy. Lasers may
      be best used in combination with other therapies to enhance their results.
      Photodynamic therapy has been successful with substances such as 5-aminolevulinic
      acid and indocyanine green. Lasers remain viable alternatives for people who may
      not desire or be able to use topical or systemic formulations. Drawbacks
      associated with lasers include potential pain, skin discoloration, and cost of
      treatment. Typically, multiple sessions are required to achieve the desired
      results, with future maintenance treatments possible to maintain the outcomes.
      With additional clinical trials underway, laser treatment of acne will surely
      advance and continue to be optimized in the future.

PMID- 16427504
TI  - Use of the 308-nm excimer laser for psoriasis and vitiligo.
AB  - The 308-nm excimer laser represents the latest advance in the concept of
      selective phototherapy. It emits a wavelength in the UV-B spectrum and thus
      shares the same indications as conventional phototherapy. Like other laser
      devices, the 308-nm excimer laser emits a monochromatic and coherent beam of
      light, can selectively treat a lesion while sparing surrounding healthy skin, and
      can deliver high fluencies. Clinicians have taken advantage of these properties
      to treat dermatologic disorders since 1997, with psoriasis and vitiligo
      attracting most attention. Initially, high fluencies (minimal erythemal dose, 8
      16) were used, with excellent clinical results, to treat psoriasis vulgaris. The
      significance of side effects and the potential long-term carcinogenic risk
      associated with such fluencies have resulted in medium doses (about 3 minimal
      erythemal dose) being recommended, however. Interestingly, taking advantage of
      the selectivity of the laser, newer treatment protocols adapt the dose to the
      lesion and not to the minimal erythemal dose, as is the case for conventional
      phototherapies. Many prospective study series have also shown the efficacy and
      the good tolerance of the 308-nm excimer laser in the treatment of localized
      vitiligo. Induced rates of repigmentation seem to be higher than with narrowband
      UV-B. Moreover, the selectivity of the treatment prevents irradiation of healthy
      skin and limits unsightly tanning of surrounding skin. Aesthetically pleasing
      results are usually not achieved in extremities and bony prominences, which are
      not good indications for this technique. Combining the 308-nm excimer laser with
      0.1% tacrolimus ointment has provided very interesting results, which need to be
      confirmed in larger series. The absence of actual data concerning the long-term
      risk for skin cancer after this treatment means that it should be considered with
      caution. Combination with topical steroids appears to be synergistic and
      potentially reduces long-term side effects; again, prospective data are lacking.

PMID- 16427505
TI  - Laser treatment of tattoos.
AB  - Tattooing has been around since the early beginnings of modern civilization.
      Modern tattoo artists use a myriad of colors to produce striking designs,
      resulting in permanent works of body art; however, we humans have been changing
      our minds since the beginning of time. Our fickle nature results in the desire to
      change what has been placed as a permanent reminder of a friend, spouse, or work
      of art. Removing tattoos began with abrasive and destructive measures to destroy
      the tattoo, and unfortunately, the skin it was contained in. The discovery of
      selective photothermolysis, the ability to selectively remove target structures
      without disrupting the surrounding skin, made it at least possible to remove
      tattoos without destroying the surrounding skin leaving a scar. Theory predicted
      that pulse durations in the nanosecond domain would be optimal for tattoo
      removal, and the Q-switched neodymium:yttrium-aluminum-garnet, alexandrite, and
      ruby lasers fulfilled this need. Too often, older lasers or intense pulsed light
      sources are used to treat tattoos, often with significant scarring. Since the
      advent of the Q-switched lasers more than a decade ago, improvement in tattoo
      removal lasers has been incremental. Developments leading to new tattoo inks,
      feedback systems to detect the absorbance characteristics of tattoo inks, dermal
      clearing agents, and perhaps even shorter pulse-duration lasers should result in
      improved results for the future.

PMID- 16427506
TI  - Legal issues in laser operation.
AB  - Dermatologic laser surgery is a continuously evolving field of medicine.
      According to the American Society for Dermatologic Surgery, in 2003, more than
      100 million laser and light source cosmetic procedures were performed by its
      members. Procedures including hair removal and nonablative treatments, as well as
      removal of pigmented lesions, tattoos, and unwanted vascular lesions have
      revolutionized this field. With an increasing number of physicians and
      nonphysicians performing these procedures and with the availability of
      increasingly powerful laser technologies, the potential for problems and their
      legal consequences continue to increase. This chapter will deal with the concept
      of negligence and the potential for a resultant medical malpractice that may
      arise in such a setting. Inherent in this issue are the associated problems that
      arise when these procedures are performed by physician extenders. An
      understanding of the basic principals of a cause of action in medical malpractice
      will likely protect a physician from losing such a case in a court of law. The
      impact of the physician-physician extender relationship and the legal issues that
      arise from this relationship will also be discussed.

PMID- 16427507
TI  - IV World Congress of the International Academy of Cosmetic Dermatology July 2 to
      5, 2005, Paris, France.

PMID- 16427508
TI  - Argyria: my life story.

PMID- 16427510
TI  - Maurizio Binazzi.

PMID- 16427511
TI  - Changes in microbial and soil properties following amendment with treated and
      untreated olive mill wastewater.
AB  - We investigated the effect of untreated and biologically treated olive mill
      wastewater (OMW) spreading on the soil characteristics and the microbial
      communities. The water holding capacity, the salinity and the content of total
      organic carbon, humus, total nitrogen, phosphate and potassium increased when the
      spread amounts of the treated or untreated OMW increased. The OMW treated soil
      exhibited significantly higher respiration compared to the control soil. However,
      the C-CO2/C(tot) ratio decreased from 1.7 in the control soil to 0.5 in the soil
      amended with 100 m3 ha(-1) of untreated OMW. However, it slightly decreased to
      1.15 in the soil amended with 400 m3 ha(-1) of treated OMW. The treated OMW
      increased the total mesophylic number while the number of fungi and nitrifiers
      decreased. Actinomycetes and spore-forming bacteria were neither sensitive to
      treated nor to untreated OMW. The total coliforms increased with higher doses of
      treated and untreated OMW. A toxic effect of the untreated OMW appeared from 100
      m3 ha(-1). This toxicity was more significant with 200 m3 ha(-1), where
      microflora of total mesophilic, yeasts and moulds, actinomycetes, and nitrifiers
      were seriously inhibited except for total coliforms and spore-forming bacteria.

PMID- 16427512
TI  - Effect of medium components on bacteriocin production by Lactobacillus plantarum
      strains ST23LD and ST341LD, isolated from spoiled olive brine.
AB  - Bacteriocin ST23LD levels of 2930AU/OD were recorded in MRS broth (pH of 6.5) and
      in the presence of tryptone and yeast extract as sole nitrogen sources. Growth in
      MRS broth at an initial pH of 6.0 yielded only 1460AU/OD bacteriocin ST23LD.
      Activities of 5861AU/OD were recorded with maltose (20, 30 and 40 g/l) as sole
      carbon source and 9036AU/OD with the addition of 2.0-10.0 g/l KH2PO4. Bacteriocin
      ST341LD levels of 2850 and 2841AU/OD were recorded in MRS broth at an initial pH
      of 6.0 or 5.5, respectively. Only 709AU/OD was recorded in the same medium with
      an initial pH of 6.5. Bacteriocin ST341LD production was stimulated by the
      presence of tryptone. However, glucose at 10 and 40 g/l, or the presence of 5.0
      or 10.0 g/l K2HPO4, resulted in a 50% reduction of bacteriocin activity. Glycerol
      in the growth medium repressed bacteriocin production. No increased bacteriocin
      production was recorded in medium supplemented with vitamins.

PMID- 16427513
TI  - Cytolethal distending toxin generates cell death by inducing a bottleneck in the
      cell cycle.
AB  - Cytolethal distending toxin (CDT) is a bacterial protein that is widely
      distributed among gram-negative bacteria including Escherichia coli,
      Campylobacter spp., enterohepatic Helicobacter spp., Actinobacillus
      actinomycetemcomitans and Haemophilus ducreyi. In vitro studies demonstrated that
      it is able to stop proliferation of various cell lines. The toxin is composed of
      three subunits designated CDTs A, B and C. The B subunit targets the eukaryotic
      DNA and triggers a signalling pathway involving different protein kinases which
      results in a cell block before entering into mitosis. To date, the individual
      role of the A and C subunits has not been totally elucidated. There are
      indications that the CDT is also produced in vivo. Its exact role in pathogenesis
      is not yet clear, but possible actions include inhibition of epithelial cell
      proliferation, apoptosis of immune cells and inhibition of a fibrotic response.

PMID- 16427514
TI  - Dibutyl phthalate, the bioactive compound produced by Streptomyces albidoflavus
      321.2.
AB  - It was found that the bioactive compound, dibutyl phthalate, was produced by a
      new soil isolate Streptomyces albidoflavus 321.2. Once this active compound was
      recovered by ethyl acetate from the fermented broth, being possible to isolate
      13.4 mg/l, it was purified by paper, silica gel column, thin layer and gas
      chromatography. Structure was determined by analysing UV, IR and GC-MS spectra.
      During analysis, such active compound showed strong activity against gram
      positive and gram-negative bacteria, as well as unicellular and filamentous
      fungi. The antimicrobial activity of the compound was reversed by the amino acid
      proline. No acute toxicity was observed.

PMID- 16427515
TI  - Antimicrobial activities of some Bacillus spp. strains isolated from the soil.
AB  - In this study a total of 29 Bacillus species isolated from the soil was analyzed
      using the agar diffusion method in terms of their general inhibition effects to
      some test bacteria. It has been found that isolates are effective against gram
      positive and gram-negative bacteria whereas their extensive inhibition effect is
      particularly against gram-positive bacteria. On the other hand, B. cereus M15
      strain has an inhibitory effect against both gram-positive and gram-negative
      bacteria. Furthermore some isolates are more effective against test bacteria when
      compared to some antibiotics.

PMID- 16427516
TI  - Denitrification by the mix-culturing of fungi and bacteria with shell.
AB  - Denitrification by pure and mixed culture of Fusarium oxysporum and Pseudomonas
      stutzeri in different mineral medium and in synthetic wastewater were examined.
      The results obtained revealed that a rapid N2 evolution by F. oxysporum and P.
      stutzeri in mineral medium and synthetic wastewater was observed. In co-cultures
      of F. oxysporum and P. stutzeri, N2O produced by F. oxysporum was rapidly
      consumed by P. stutzeri. This indicated that mixed culture of F. oxysporum and P.
      stutzeri could be used for efficient nitrate and nitrite removal. Using synthetic
      wastewater, about 87% of nitrate was reduced by co-denitrification of F.
      oxysporum and P. stutzeri after incubation for 6 days. In the further
      denitrification tests, the interaction of shell and mixed culture of F. oxysporum
      and P. stutzeri was investigated. The dinitrogen was rapidly evolved (442.48
      micromol N2 produced from 1.0 mmol of NO3(-) in 36 h). These results clearly
      showed that shell provide a suitable microenvironment for P. stutzeri, which is
      beneficial to the denitrification.

PMID- 16427517
TI  - Site-directed mutagenesis of gentisate 1,2-dioxygenases from Klebsiella
      pneumoniae M5a1 and Ralstonia sp. strain U2.
AB  - Gentisate 1,2-dioxygenase (GDO, EC 1.13.11.4) is the first enzyme in gentisate
      pathway that catalyses the ring fission of gentisate to form maleylpyruvate.
      Phylogenetic tree of amino acid sequences from 11 GDOs demonstrates that the GDOs
      from different genus share identities between 12.1% and 64.8%. According to the
      alignment result, four highly conserved histidine residues in GDO from Klebsiella
      pneumoniae M5a1 and Ralstonia sp. strain U2 were chosen to be substituted with
      aspartate residues. Enzyme analysis indicated that substitution of any of these
      four histidine residues had resulted in the complete loss of its catalytic
      activity.

PMID- 16427518
TI  - Sensitive and specific detection of Xanthomonas axonopodis pv. citri by PCR using
      pathovar specific primers based on hrpW gene sequences.
AB  - A sensitive and specific assay was developed to detect citrus bacterial canker
      caused by Xanthomonas axonopodis pv. citri, in leaves and fruits of citrus.
      Primers XACF and XACR from hrpW homologous to pectate lyase, modifying the
      structure of pectin in plants, were used to amplify a 561 bp DNA fragment. PCR
      technique was applied to detect the pathogen in naturally or artificially
      infected leaves of citrus. The PCR product was only produced from X. axonopodis
      pv. citri among 26 isolates of Xanthomonas strains, Escherichia coli (O157:H7),
      Pectobacterium carotovorum subsp. carotovorum, and other reference microbes.

PMID- 16427520
TI  - Comparison of the SYBR Green and the hybridization probe format for real-time PCR
      detection of HHV-6.
AB  - A comparative study was conducted of a novel real-time quantitative PCR test
      (LightCycler System) with FastStart DNA Master(PLUS) SYBR Green I dye to detect
      DNA of human herpes virus 6 (HHV-6). Results were compared with those of a real
      time quantitative PCR with hybridization probe (HP) formats using the
      fluorescence resonance energy transfer method, and with those of a single
      qualitative PCR test. The detection limit of the test with SYBR Green I dye was
      20 copies of the virus, similar to that of the other two tests. The
      reproducibility was satisfactory. The new test has the same advantages as real
      time PCR with HP formats and offers a greater versatility at lower cost.

PMID- 16427519
TI  - Genetic diversity of bacterial strains isolated from soils, contaminated with
      polycyclic aromatic hydrocarbons, by 16S rRNA gene sequencing and amplified
      fragment length polymorphism fingerprinting.
AB  - In order to study microbial diversity in a polycyclic aromatic hydrocarbon
      impacted soil, 14 bacterial strains were analyzed by 16S rRNA gene sequencing and
      amplified fragment length polymorphism (AFLP) analysis. Bacterial strains
      isolated from two different hydrocarbon-polluted sites were identified to the
      species level by 16S rRNA full-gene sequencing using MicroSeq 16S rRNA gene
      sequencing. Their genome was subsequently analyzed by high-resolution genotyping
      with AFLP analysis, in order to monitor species variability and to differentiate
      closely related strains. Cluster analysis based on AFLP fingerprinting showed
      intra-specific polymorphism, even among strains with 100% 16S rRNA gene sequence
      identity. The results show that AFLP is a powerful, highly reproducible and
      discriminatory tool for revealing genetic relationships in bacterial populations.
      The ability to differentiate and track related closely microbes is fundamental
      for studying structure and dynamics of microbial communities in contaminated
      ecosystems.

PMID- 16427521
TI  - Peracetic acid stress-induced genetic rearrangements in Escherichia coli H10407
      detected by RAPD and RFLP analyses.
AB  - The discriminatory powers of random amplified polymorphic DNA (RAPD) analysis and
      restriction fragment length polymorphism (RFLP) were assessed for the detection
      and comparison of DNA modifications caused by an oxidative stress. DNA extracted
      from peracetic acid (PAA)-treated Escherichia coli H10407 was randomly amplified
      with the 10-mer primer OPZ14, which generated one stress-induced fragment. RFLP
      and RAPD profiles were hybridized by Southern blotting with the digoxigenin
      labelled RAPD product. Untreated and PAA-treated cells had difference band
      profiles. The results indicate that RAPD analysis could be used as a
      discriminatory tool for investigating genetic rearrangements in E. coli caused by
      oxidative stress and that RFLP analysis could be used to confirm the
      rearrangements.

PMID- 16427522
TI  - Dynamics of viable nitrifier community, N-mineralization and nitrification in
      seasonally dry tropical forests and savanna.
AB  - The study was conducted in Vindhyan region, to assess the N-mineralization,
      nitrification and size of viable community of ammonium- and nitrite-oxidizing
      bacteria as affected by different sites and seasons. Six different ecosystems
      (four forests and two savannas), which differ in terms of topography, vegetation
      and moisture status, were selected for the present study. The soils of the study
      sites differ significantly in its physico-chemical properties. The savanna site
      had significantly higher pH (7.2), bulk density (1.37 g cm(-3)) and silt content
      (67.80%) but lower water holding capacity (1.37%), total-C (16,356 microg g(-1)
      dry soil), N (1090 microg g(-1) dry soil) and P (213 microg g(-1) dry soil) than
      forest sites. The soil moisture content, N-mineralization, nitrification rates
      and numbers of ammonium- and nitrite-oxidizing bacteria were highest in the wet
      season and lowest in dry season, while the size of mineral-N (NH4(+)-N and NO3(-)
      N) showed a reverse trend at the sites. The N-mineralization, nitrification and
      nitrifier population size differ significantly across the site and season. The
      numbers of free-living cells of ammonium- and nitrite-oxidizing bacteria were
      significantly related to each other and to N-mineralization, nitrification, soil
      moisture and mineral-N components. The N-mineralization, nitrification and the
      viable number of nitrifying cells were consistently higher for forest soils
      compared to savanna sites. It was concluded that soil microbial process (N
      mineralization and nitrification) and nitrifier population size were dependent on
      site topography, vegetation cover and soil moisture status.

PMID- 16427523
TI  - Antialgal, antibacterial and antifungal activity of two metabolites produced and
      excreted by cyanobacteria during growth.
AB  - The antimicrobial activity of two cyanobacterial exometabolites, norharmane (9H
      pyrido(3,4-b)indole) and 4,4'-dihydroxybiphenyl, was determined in suspension
      assays. Good anticyanobacterial activities (concentrations of 8-80 microg ml(-1))
      and moderate antibacterial (16-160 microg ml(-1)) and antifungal (32-40 microg
      ml(-1)) activities were found for both compounds. The natural function as
      allelopathic chemicals and a possible applicability as antifouling agents or
      leads for the development of new antifouling chemicals are discussed.

PMID- 16427525
TI  - Effects of morphine and its metabolites on immune function in advanced cancer
      patients.
AB  - STUDY OBJECTIVE: To determine whether morphine and its active metabolites such as
      morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) modulate immune
      function in patients with advanced cancer who required morphine for pain relief.
      DESIGN: Prospective observational clinical study. SETTING: Pain clinic of a
      university hospital. PATIENTS: Fifteen patients who visited our clinic for
      control of advanced cancer pain. INTERVENTIONS: During the initiation or changes
      of morphine therapy, venous blood samples were obtained at the enrollment of this
      study, 1 and 3 weeks after the change of morphine dose or route. MEASUREMENTS:
      Lymphocyte subpopulation CD4+ and CD8+, activity of natural killer cell,
      phytohemagglutinin (PHA)-induced T-cell proliferation, and plasma immunoglobulin
      M and G concentrations were measured, as well as plasma concentrations of
      morphine, M-3-G, and M-6-G. MAIN RESULTS: At the entry of the study, 6 patients
      did not receive any type of morphine medication (group 1), whereas 9 patients
      were treated with morphine for 1 month (group 2). Cancer pain, rated as 4 at the
      entry period, was reduced to 2 of 10 (visual analogue scale) during the study
      periods. Although the plasma concentrations of M-3-G and M-6-G in Group 1 were
      significantly less than those in Group 2, plasma concentrations of immunologic
      markers were similar between the groups. In Group 1, Spearman linear regression
      analysis showed negative correlation between morphine-derived metabolites and
      immunoglobulins or PHA-induced T-cell proliferation, whereas poor correlation was
      found with all immunologic parameters in Group 2. Stepwise linear regression
      analyses showed that the metabolites, rather than morphine per se, modulated
      immune function, reflected by PHA-induced T-cell proliferation and immunoglobulin
      G concentration in Group 1. CONCLUSIONS: The present study suggests that some of
      humoral and cellular immunity are modulated by morphine-derived metabolites at
      the early phase of morphine therapy in patients with advanced cancer.

PMID- 16427526
TI  - Anesthesia with 1.5 minimum alveolar concentration sevoflurane is not altered by
      physostigmine as measured by bispectral and clinical indices.
AB  - STUDY OBJECTIVE: To evaluate the effect of physostigmine on 1.5% sevoflurane
      anesthesia and recovery. DESIGN: Prospective, randomized, double-blinded study.
      SETTING: Operating room of a university-affiliated, metropolitan hospital
      (Aretaieion Hospital and St Savas Hospital). PATIENTS: Forty female American
      Society of Anesthesiologists physical status I and II patients scheduled for
      breast biopsy. INTERVENTIONS: Patients were randomly assigned in physostigmine
      (PHYSO) and normal-saline (NS) group. Anesthesia was induced with sevoflurane 8%
      using a vital capacity breath technique, and rocuronium 0.6 mg/kg was given to
      facilitate Laryngeal Mask Airway (LMA) No. 4 insertion. Anesthesia was maintained
      with end-tidal sevoflurane 1.5 minimum alveolar concentration (MAC; 3% end-tidal
      concentration) throughout the procedure. MEASUREMENTS: After skin closure and
      under steady-state sevoflurane anesthesia 1.5 MAC, heart rate, blood pressure,
      and Bispectral Index (BIS) were recorded. Immediately after, the PHYSO group
      received intravenous 2 mg of physostigmine, whereas the NS group received equal
      volume of normal saline. Bispectral Index and hemodynamic measurements were
      recorded 5, 8, and 10 minutes after treatment. Anesthesia was then discontinued
      and the LMA was removed. Zero, 15, and 30 minutes after LMA removal, patients
      were evaluated for orientation, sedation, sitting ability, and the "picking up
      matches" test, as well as for nausea and vomiting. MAIN RESULTS: No difference
      was found in BIS (29 +/- 4, 32 +/- 6, 31 +/- 6, 30 +/- 7, 84 +/- 11 in the PHYSO
      group vs 29 +/- 6, 30 +/- 6, 30 +/- 5, 31 +/- 5, 86 +/- 7 in the NS group),
      hemodynamic parameters, or recovery parameters between the 2 groups at any time.
      No nausea or vomiting was observed in either group. CONCLUSIONS: Physostigmine
      did not influence BIS values or early recovery when administered to patients
      anesthetized with 1.5 MAC sevoflurane anesthesia.

PMID- 16427527
TI  - Stress hormone changes in general anesthesia of long duration: isoflurane-nitrous
      oxide vs sevoflurane-nitrous oxide anesthesia.
AB  - STUDY OBJECTIVE: There are few comparative studies of stress hormone changes
      during general anesthesia with long duration between isoflurane-nitrous oxide and
      sevoflurane-nitrous oxide anesthesia. We investigated perioperative changes of
      stress hormone in these two anesthetic methods with duration of more than 10
      hours. DESIGN: Prospective study. SETTING: Operating room and high care unit of a
      university hospital. PATIENTS: Twenty patients with ASA physical status I or II
      for surgery for laryngeal or pharyngeal cancer with expected duration of more
      than 10 hours. INTERVENTIONS: Anesthesia was induced with midazolam, thiopental,
      and vecuronium and was maintained with sevoflurane (sevoflurane group) or
      isoflurane (isoflurane group) with nitrous oxide 4 L/min in oxygen 2 L/min.
      MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of epinephrine,
      norepinephrine, cortisol, adrenocorticotropic hormone, and anti-diuretic hormone
      (ADH); serum concentrations of glucagon and insulin; and blood glucose
      concentration were measured before inhalation of anesthetics, after 5 and 10
      hours, and at 1, 6, and 12 hours after the end of inhalation. Epinephrine and
      norepinephrine concentrations increased continuously during and after surgery in
      the isoflurane group whereas it increased only after surgery in the sevoflurane
      group. Both concentrations were higher in the isoflurane group during anesthesia.
      Cortisol increased continuously whereas adrenocorticotropic hormone increased
      only during surgery. Anti-diuretic hormone increased with its peak during surgery
      and the isoflurane group had significantly higher values than the sevoflurane
      group. Glucose increased both during and after surgery, insulin increased only
      after surgery, and glucagon decreased during surgery in both groups. CONCLUSIONS:
      In inhalation anesthesia with the duration of more than 10 hours, isoflurane
      nitrous oxide and sevoflurane-nitrous oxide had the same effects on stress
      hormone changes except for epinephrine, norepinephrine, and ADH. Epinephrine,
      norepinephrine, and ADH concentrations were higher in isoflurane-nitrous oxide
      anesthesia.

PMID- 16427528
TI  - The influence of timing of systemic ketamine administration on postoperative
      morphine consumption.
AB  - STUDY OBJECTIVE: To determine the influence of timing of systemic ketamine
      administration on postoperative morphine consumption. DESIGN: Prospective
      randomized study. SETTING: Operating rooms, postanesthesia care unit, and
      gynecology service of a university hospital. PATIENTS: Forty-five patients
      undergoing laparotomy for benign gynecologic pathologies were randomized into 3
      groups. INTERVENTIONS: In Group 1, before surgical incision, patients received
      0.5 mg/kg ketamine IV, followed by normal saline infusion and normal saline IV at
      wound closure in group 1 (n = 15). In group 2 (n = 15), patients received 0.5
      mg/kg ketamine IV before surgery, followed by ketamine infusion 600 mug . kg(-1)
      . h(-1), until wound closure and normal saline IV at that time. In the other
      group (group 3, n = 15), patients received normal saline IV before surgery,
      followed by saline infusion and then 0.5 mg/kg ketamine IV at wound closure. In
      the postoperative period, patient-controlled analgesia IV morphine was used for
      postoperative pain relief. First requested analgesic medication time was
      recorded. Postoperative pain was assessed by measuring morphine consumption at 0
      to 2, 0 to 4, and 0 to 24 hours and visual analog scale (VAS) pain scores in
      response to cough at 2nd, 4th, and 24th hours and during rest at 0 to 2, 0 to 4,
      and 0 to 24 hours after surgery. MEASUREMENT AND MAIN RESULTS: First requested
      analgesia was shorter in group 1 than the others (P < .01). Mean VAS pain scores
      in response to cough at 24th hour in groups 2 and 3 were significantly lower than
      in group 1 (P < .001 and P < .01, respectively). Mean VAS pain scores during rest
      at 0 to 24 hours in groups 2 and 3 were significantly lower than in group 1 (P <
      .01 and P < .05, respectively). Morphine consumption was lower in groups 2 and 3
      at 0 to 2 hours (P < .001 and P < .01). Moreover, morphine consumption at 0 to 4
      hours in group 2 was significantly lower (P < .01). CONCLUSIONS: Lower pain
      scores and morphine consumption in groups 2 and 3 may be related to higher plasma
      ketamine concentrations caused by the higher doses and later administration. Our
      findings suggest that a single preoperative dose of ketamine provided less
      analgesia compared with other dosing regimens that included intraoperative
      infusions or postoperative administration.

PMID- 16427529
TI  - Fentanyl-induced hemodynamic changes after esophagectomy or cardiac surgery.
AB  - STUDY OBJECTIVE: The goal of this study was to characterize the hemodynamic
      response to propofol vs propofol with fentanyl when used for sedation after
      esophagectomy or cardiac surgery. DESIGN: Prospective, randomized, controlled
      study. SETTING: University Hospital, Intensive Care Unit. PATIENTS: Thirty
      patients undergoing elective cardiac surgery and 26 patients undergoing
      esophagectomy were examined. INTERVENTION: Patients were randomized to receive
      propofol (0.5 mg/kg bolus over 10 minutes, followed by continuous infusion at 1
      mg/kg per hour) with or without fentanyl (2.0 microg/kg per hour) to achieve
      sedation overnight while in the intensive care unit. Randomization was performed
      in a double-blind manner. MEASUREMENT: Mean arterial pressure (MAP) was monitored
      throughout the treatment period, and sedation level was measured. Sedation level
      was targeted to achieve a Ramsay score of 4. MAIN RESULTS: The number of patients
      experiencing a greater than 20% drop in baseline MAP was higher in cardiac
      patients receiving propofol alone (11 of 15 patients, 73%) than in cardiac
      patients receiving propofol with fentanyl (4 of 15 patients, 27%). Furthermore,
      the time of optimal sedation was lower in the cardiac patients who received
      propofol than in cardiac patients who received propofol with fentanyl group
      (propofol alone, 79%; propofol with fentanyl, 88%). In contrast, there was no
      difference in the number of esophagectomy patients experiencing a greater than
      20% drop in baseline MAP or in the mean time of optimal sedation when comparing
      the 2 treatment regimens. CONCLUSIONS: Propofol has a differential effect on
      hemodynamics and sedation when comparing patients after cardiac surgery and
      esophagectomy.

PMID- 16427530
TI  - Management of airway in patients with laryngeal tumors.
AB  - STUDY OBJECTIVE: To describe our systematic approach to securing the airway in
      patients with laryngeal tumors, developed over a 10-year period. DESIGN:
      Retrospective analysis. SETTING: University-affiliated veterans administration
      medical center. PATIENTS: Eight hundred one patients presenting for laryngeal
      tumor surgery in a 10-year period, 285 of whom underwent tracheostomy (25 with
      local anesthesia and 260 with general anesthesia). INTERVENTIONS: Preoperative
      examination, including history, physical examination, computed axial tomography
      and/or magnetic resonance imaging, and ear, nose, and throat surgeons' evaluation
      via indirect laryngoscopy or fiberoptic bronchoscopy were performed before the
      anesthesiologist's interventions. Local (topical) anesthesia and mild sedation
      were used for laryngeal evaluation with fiberoptic bronchoscopy. Tumor grade was
      then established, which determined how the airway would be secured: general
      anesthesia induction, receive topical anesthesia for awake, direct laryngoscopy,
      and tracheal intubation, or undergo tracheostomy with local anesthesia.
      MEASUREMENTS AND MAIN RESULTS: When the airway was secured, surgeons performed
      the biopsy, (any) tumor debulking, laser excision, or tracheostomy to establish
      both the airway and the diagnosis. Pulmonary function, including flow-volume
      loops and blood gas analysis were also useful in evaluating the degree of
      obstruction and gas exchange. In the event of respiratory distress, tracheostomy
      was performed after tracheal intubation or with local anesthesia, followed by
      direct laryngoscopy and biopsy. Depending on the diagnosis, further surgery and
      radiation treatment were planned next. CONCLUSIONS: With these guidelines, we
      have reduced the frequency of emergencies because of a lost airway, bleeding, or
      dislodging of tumor.

PMID- 16427531
TI  - Anesthetic management for laser excision of recurrent respiratory papillomatosis
      in a third trimester parturient.
AB  - Recurrent respiratory papillomatosis (RRP) is characterized by the development of
      laryngeal papillomas, which can produce partial to complete upper airway
      obstruction. Patients with RRP often require intermittent surgical excision to
      treat symptoms such as hoarseness and stridor, and to control progression of the
      lesions. The anesthetic management of such patients is challenging, and it
      requires carefully coordinated care between an anesthesiologist and
      otolaryngologist. We present 2 cases of general anesthesia administration during
      surgical excision of laryngeal papillomas, both occurring during the third
      trimester of separate pregnancies in the same parturient. The complexity of
      management was amplified in these cases because of the physiological and
      anatomical changes associated with pregnancy, along with the need to monitor
      fetal well-being. Possible complications included complete airway obstruction,
      pulmonary aspiration of gastric contents, hypoxemia, fetal distress, and preterm
      labor. Because pregnancy may lead to activation of human papillomavirus, the
      causative organism of RRP, management guidelines are provided for
      anesthesiologists who may care for patients with RRP during pregnancy.

PMID- 16427532
TI  - Tracheal tube cuff perforation during ventriculoatrial shunt procedure.
AB  - We report a case of tracheal and endotracheal tube cuff perforation that occurred
      intraoperatively during a ventriculoatrial shunting procedure for a patient with
      normal pressure hydrocephalus. Unusual tracheal anatomy and technique were
      contributory factors. Use of noninvasive imaging devices to guide the
      intraoperative placement of catheters may avoid many of the complications related
      to anatomy, skill, and technique. The method of diagnosis, prevention, and
      management is discussed.

PMID- 16427533
TI  - Transesophageal echocardiographic and oxymetric evidence of intraoperative
      reversal of flow through a patent foramen ovale during an off-pump coronary
      artery bypass grafting.
AB  - Mechanical stabilization of target coronary arteries in the beating heart has
      facilitated the practice of "off-pump" coronary artery bypass grafting. Exposing
      the target coronary artery for stabilization involves maneuvers that frequently
      cause hemodynamic alterations including decreased cardiac output and increased
      pulmonary artery and/or central venous pressures (CVP). The presence of a patent
      foramen ovale (PFO) in the setting of increased CVP may produce a right-to-left
      shunt through the PFO. We report a case of a patient undergoing off-pump coronary
      artery bypass grafting with a PFO with a left to right atrium shunt flow of 307
      mL/min. During manipulation and elevation of the heart to expose the target
      vessel, the CVP increased from 15 to 30 mm Hg and the shunt through the PFO
      reversed direction, going from right to left atrium with a flow of 161 mL/min.
      Mixed venous oxygen saturation and the calculated shunt fraction decreased from
      84% to 78% and 14% to 10%, respectively. All parameters returned to normal after
      the heart was lowered back inside the chest.

PMID- 16427534
TI  - The use of peripheral nerve blocks at the elbow for carpal tunnel release.
AB  - This case report illustrates that median, radial, and ulnar nerve blocks at the
      elbow provides anesthesia for ambulatory carpal tunnel release surgery. This
      report discusses 3 patients with medical conditions, including vascular access
      problems and morbid obesity, which made nerve blocks at the elbow advantageous
      compared with other anesthetic techniques. Peripheral nerve blocks at the elbow
      were done before surgery in a block room, so the patients spent less time in the
      operating room. Nerve blocks at the elbow are effective anesthesia for hand
      procedures with no patient requiring further local anesthetic injection and
      opioids for pain or expressing any discomfort during surgery. The blocks are easy
      to perform and set up quickly, and using long-acting local anesthetics, elbow
      blocks provide postoperative pain control for approximately 10 hours. The nerve
      blocks at the elbow facilitate the perioperative process by being done out of the
      operating room and providing prolonged pain control without the need for opioids,
      so nausea may be avoided.

PMID- 16427535
TI  - Anesthesia for an adult with mucopolysaccharidosis I.
AB  - We describe the anesthetic management difficulties of a man with
      mucopolysaccharidosis I. We also briefly review the anesthesia literature related
      to this disease.

PMID- 16427536
TI  - Anesthetic implications of traumatic pulmonary hernia repair.
AB  - Traumatic pulmonary herniation involves the protrusion of lung parenchyma beyond
      the normal borders of the thoracic cage through a defect in the musculoskeletal
      wall. Anesthetic management involves airway protection, lung isolation, and
      avoidance of distension of the herniated segment. We report the successful
      anesthetic management during surgical management of pulmonary herniation.

PMID- 16427537
TI  - Significant hyperkalemia after discontinuation of an insulin pump.
AB  - Patients with diabetes and insulin pumps may need their insulin therapy modified
      during surgery. Often, this is done with blood glucose as the end point. Changing
      insulin therapy can also have profound effects on potassium homeostasis in
      certain patients. This case demonstrates that changes in insulin therapy warrant
      not only close monitoring of blood glucose, but also of serum potassium. This
      patient's comorbidities and treatments that could alter potassium homeostasis are
      also reviewed.

PMID- 16427538
TI  - Anaphylaxis to isosulfan blue dye during sentinel lymph node biopsy.
AB  - We describe a case of intraoperative anaphylaxis resulting from isosulfan blue
      (IB) dye, an agent being increasingly used for identification of sentinel lymph
      nodes. A 45-year-old woman undergoing a left mastectomy with sentinel lymph node
      biopsy under general endotracheal anesthesia developed severe intraoperative
      hypotension and tachycardia 10 minutes after subcutaneous injection of IB dye for
      lymphatic mapping. This was associated with a reduction in pulse oximeter reading
      to 89%. She was successfully resuscitated using 1 mg of epinephrine intravenously
      (IV). Invasive arterial and central venous pressures were initiated; her lymph
      node biopsy was concluded, but the rest of her procedure was canceled.
      Postoperative workup revealed a high tryptase level indicative of an
      intraoperative anaphylactic reaction most probably related to the IB dye.
      Isosulfan blue dye can act as an antigen, causing a full-blown intraoperative
      anaphylactic reaction. Early recognition and aggressive hemodynamic interventions
      can reduce morbidity and mortality.

PMID- 16427539
TI  - Short-term noninvasive ventilation in the postanesthesia care unit: a case
      series.
AB  - Eight patients suffering various causes of transient postoperative respiratory
      failure in the postanesthesia care unit were treated with short-term noninvasive
      pressure-support ventilation administered through a tight-fitting face mask.
      Intubation was avoided in all of them, and no complications were observed, as
      assessed by the treating anesthesiologist and from review of their charts.
      Indications and advantages of noninvasive ventilation in the early postoperative
      period are discussed.

PMID- 16427540
TI  - Caring for the patients with cervical spine injuries: what have we learned?
AB  - PURPOSE: Anesthesiologists are often involved in the early management and
      resuscitation of patients who have sustained cervical spine injuries (CSIs). The
      most crucial step in managing a patient with suspected CSI is the prevention of
      further insult to the cervical spine (C-spine). In this review, important factors
      related to initial management, diagnosis, airway and anesthetic management of
      patients with CSI are presented. SOURCE: Medline search was performed to seek out
      the English-language literature using the following phrases and keywords: spine
      trauma; cervical spine; airway management after CSI. PRINCIPAL FINDINGS: Cervical
      spine injury occurs in up to 3% to 6% of all patients with trauma. The initial
      management of a patient with potential spine injury requires a high degree of
      suspicion for CSI so that early stabilization of the spine can be used to prevent
      further neurological damage. Diagnostic radiology has a critical role to play;
      however, clinical evaluation is equally important in excluding CSI in a conscious
      and cooperative patient. Although in-line stabilization reduces the movement at C
      spine, traction causes clinically significant distraction and should be avoided.
      CONCLUSION: A high level of suspicion and anticipation are the major components
      of decision making and management in a patient with CSI. Endotracheal intubation
      using the Bullard laryngoscope may have some advantages over other techniques as
      it causes less head and C-spine extension than the conventional laryngoscope, and
      this results in a better view. However, the current opinion is that oral
      intubation using a Macintosh blade after intravenous induction of anesthesia and
      muscle relaxation along with inline stabilization is the safest and quickest way
      to achieve intubation in a patient with suspected CSI. In summation caution,
      close care and maintenance of spinal immobilization are more important factors in
      limiting the risk of secondary neurological injury than any particular technique.

PMID- 16427541
TI  - Educating Jehovah's Witness patients.

PMID- 16427543
TI  - Ischemic preconditioning for major liver resection under vascular exclusion of
      the liver preserving the caval flow: a randomized prospective study.
AB  - BACKGROUND: Two randomized prospective studies suggested that ischemic
      preconditioning (IP) protects the human liver against ischemia-reperfusion injury
      after hepatectomy performed under continuous clamping of the portal triad. The
      primary goal of this study was to determine whether IP protects the human liver
      against ischemia-reperfusion injury after hepatectomy under continuous vascular
      exclusion with preservation of the caval flow. STUDY DESIGN: Sixty patients were
      randomly divided into two groups: with (n=30; preconditioning group) and without
      (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of
      reperfusion) before major hepatectomy under vascular exclusion of the liver
      preserving the caval flow. Serum concentrations of aspartate transferase, alanine
      transferase, glutathione-S-transferase, and bilirubin and prothrombin time were
      regularly determined until discharge and at 1 month. Morbidity and mortality were
      determined in both groups. RESULTS: Peak postoperative concentrations of
      aspartate transferase were similar in the groups with and without IP (851 +/-
      1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a
      higher peak concentration of alanine transferase and glutathione-S-transferase
      was indeed observed in the preconditioning group compared with the control group.
      Morbidity and mortality rates and lengths of ICU and hospitalization stays were
      similar in both groups. CONCLUSIONS: IP does not improve liver tolerance to
      ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with
      preservation of the caval flow. This maneuver does not improve postoperative
      liver function and does not affect morbidity or mortality rates. The clinical use
      of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not
      currently recommended.

PMID- 16427544
TI  - Relationship between American College of Surgeons trauma center designation and
      mortality in patients with severe trauma (injury severity score > 15).
AB  - BACKGROUND: We studied the association of the American College of Surgeons (ACS)
      trauma center designation and mortality in adult patients with severe trauma
      (Injury Severity Score > 15). ACS designation of trauma centers into different
      levels requires substantial financial and human resources commitments. There is
      very little work published on the association of ACS trauma center designation
      and outcomes in severe trauma. STUDY DESIGN: National Trauma Data Bank study
      including all adult trauma admissions (older than 14 years of age) with Injury
      Severity Score (ISS) > 15. The relationship between ACS level of trauma
      designation and survival outcomes was evaluated after adjusting for age,
      mechanism of injury, ISS, hypotension on admission, severe liver trauma, aortic,
      vena cava, iliac vascular, and penetrating cardiac injuries. RESULTS: A total of
      130,154 patients from 256 trauma centers met the inclusion criteria. Adjusted
      mortality in ACS-designated Level II centers and undesignated centers was notably
      higher than in Level I centers (adjusted odds ratio, 1.14; 95% CI, 1.09-120; p <
      0.0001 and adjusted odds ratio, 1.09; CI, 1.05-1.13; p < 0.0001, respectively).
      CONCLUSIONS: Severely injured patients with ISS > 15 treated in ACS Level I
      trauma centers have considerably better survival outcomes than those treated in
      ACS Level II centers.

PMID- 16427545
TI  - A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for
      reducing blood loss in coronary artery bypass grafting surgery.
AB  - BACKGROUND: Epsilon-aminocaproic acid is a plasmin inhibitor that potentially
      reduces perioperative bleeding when administered prophylactically to cardiac
      surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a
      prospective placebo-controlled trial was conducted in patients undergoing primary
      coronary artery bypass grafting surgery. STUDY DESIGN: One hundred patients were
      randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before
      skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g
      in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon
      aminocaproic acid was evaluated by the reduction in postoperative thoracic
      drainage volume and in donor-blood transfusion up to postoperative day 12.
      RESULTS: Postoperative thoracic-drainage volume was significantly lower in the
      epsilon-aminocaproic acid group compared with the placebo group (epsilon
      aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003).
      There were no significant differences between the epsilon-aminocaproic acid and
      placebo groups in the percentage of patients requiring donor red blood cell
      transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in
      the number of units of donor red blood cells transfused (epsilon-aminocaproic
      acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic
      acid did not reduce the risk of donor red blood cell transfusions compared with
      placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63).
      CONCLUSIONS: Prophylactic administration of epsilon-aminocaproic acid reduces
      postoperative thoracic-drainage volume by 30%, but it may not be potent enough to
      reduce the requirement and the risk for donor blood transfusion in cardiac
      surgery patients. This information is useful for deciding on a therapy for
      hemostasis in cardiac surgery.

PMID- 16427546
TI  - Surgical outcomes in patients with T4 gastric carcinoma.
AB  - BACKGROUND: There is controversy about the best therapeutic surgical approach for
      treatment of patients with T4 gastric cancer. STUDY DESIGN: We used univariate
      and multivariate analyses to review the surgical outcomes and prognostic factors
      of 117 patients who underwent surgery for T4 gastric carcinoma. RESULTS: Curative
      resection was performed in 38 (32.4%) patients, with the pancreas being the most
      frequently resected organ. The 5-year survival rate was 16.0% and the median
      survival time (MST) was 11 months for all 117 registered patients. The 5-year
      survival rates and MSTs in patients after curative and noncurative resection were
      32.2% versus 9.5% and 20 months versus 8 months, respectively. These values
      differed considerably between the two groups (p < 0.0001). Curability was an
      independent prognostic factor among all registered patients, including those who
      underwent noncurative resection. A relatively small tumor diameter (< 100 mm) and
      few lymph node metastases (six or fewer metastatic lymph nodes) were independent
      prognostic factors when curative resection could be performed. Postoperative
      morbidity and mortality were acceptable after curative combined resection.
      CONCLUSIONS: We recommend the use of aggressive combined resection of adjacent
      organs, with extended lymph node dissection, for patients with T4 gastric
      carcinoma in whom curative resection can be used; that is, those with few
      metastatic lymph nodes (six or less) and a relatively small tumor diameter (100
      mm). But noncurative resection should be avoided in patients with T4 gastric
      cancer.

PMID- 16427547
TI  - Prognostic significance of intraperitoneal cancer cells in gastric carcinoma:
      analysis of real time reverse transcriptase-polymerase chain reaction after 5
      years of followup.
AB  - BACKGROUND: The presence of gastric cancer cells in the peritoneal cavity
      detected by cytologic examination is an important prognostic factor. A reverse
      transcriptase-polymerase chain reaction (RT-PCR) technique amplifying
      carcinoembryonic antigen mRNA was recently introduced to detect these cells more
      sensitively. STUDY DESIGN: Five-year followup was completed for 284 gastric
      carcinoma patients who underwent CEA RT-PCR testing. Analyses to assess the
      accuracy and prognostic value of this procedure were performed, along with
      univariate and multivariable analyses to evaluate RT-PCR as a technique with
      peritoneal carcinomatosis and cancer death as the outcomes variables. RESULTS:
      CEA mRNA levels exceeded the cutoff value defining a positive result in 9.5%,
      29%, 66%, and 81% of patients with pT1, pT2, pT3, and pT4 stage disease,
      respectively. Sensitivity, specificity, positive predictive value, and negative
      predictive value for peritoneal carcinomatosis within 5 years of surgery were
      88.5%, 81.6%, 64.5%, and 94.9%, respectively. Multivariable analysis revealed
      that a positive CEA mRNA result was an independent risk factor for cancer death
      (hazard ratio 2.82, 95% CI 1.17 -3.07) among 274 patients (10 patients with no
      record of nodal status were excluded from the analysis) and for peritoneal
      carcinomatosis (hazard ratio 1.57, 95% CI 1.07-2.29) among 242 patients who had
      no peritoneal deposits at operation. CONCLUSIONS: CEA RT-PCR is useful as a
      prognostic marker for increased risk of cancer death and peritoneal
      carcinomatosis, and might be useful in the clinical setting for selecting
      patients for various adjuvant treatments.

PMID- 16427549
TI  - Variation in treatment of pediatric spleen injury at trauma centers versus
      nontrauma centers: a call for dissemination of American Pediatric Surgical
      Association benchmarks and guidelines.
AB  - BACKGROUND: American Pediatric Surgical Association consensus guidelines for
      children with blunt spleen injuries have been defined and validated in children's
      hospitals, but large administrative data sets indicate that only 10% to 15% of
      children with blunt spleen injuries are treated at children's hospitals. We
      sought to identify the frequency and compare the treatment of children with
      spleen injury in hospitals with and without recognized trauma expertise, with the
      aim of identifying a meaningful target for dissemination of benchmarks and
      consensus guidelines. STUDY DESIGN: State health departments' administrative data
      sets from California, Florida, New Jersey, and New York were analyzed for 2000,
      2001, and 2002. All children with head injury or other nonspleen abdominal
      injuries requiring surgery were excluded. Injury Severity Scores were determined
      by ICDMAP-90. RESULTS: There were 3,232 patients with blunt spleen injury. Trauma
      centers had a significantly lower rate of operation for both multiply injured
      patients (15.3% versus 19.3%, p < 0.001) and those with isolated injury (9.2%
      versus 18.5%, p < 0.0001) when compared with nontrauma centers. The operative
      rates at both trauma centers and nontrauma centers exceed published American
      Pediatric Surgical Association benchmarks for all children with spleen injury (5%
      to 11%) and the subset with isolated spleen injury (0% to 3%). Independent risk
      factors for splenectomy included ages 15 to 19 years (p < 0.002), spleen injury
      severity (p < 0.0001), and presence of multiple injuries (p < 0.04). Adjusted
      odds ratio for risk of splenic operation in all patients with spleen injury was
      2.122 (95% CI:1.455- 3.096) when treated at a nontrauma center (p < 0.0001).
      CONCLUSIONS: These multistate discharge data indicate that treatment of children
      with blunt spleen injury differs significantly when comparing trauma centers and
      nontrauma centers. Because nearly two-thirds of these children were treated at
      trauma centers, dissemination of American Pediatric Surgical Association
      guidelines and benchmarks through state or regional trauma systems may reduce the
      number of children having operations for splenic injury.

PMID- 16427548
TI  - Primary tracheal malignant neoplasms: the University of Texas MD Anderson Cancer
      Center experience.
AB  - BACKGROUND: Primary malignant neoplasms of the trachea are very rare and data
      relating to them are limited. This study was conducted to review the
      presentation, management, and outcomes of primary tracheal cancers at our
      institution, a large multidisciplinary cancer center. STUDY DESIGN: Retrospective
      chart review was conducted for all patients found to have a pathologic diagnosis
      of primary tracheal malignancy. RESULTS: Since 1945, 74 patients were diagnosed
      with primary tracheal cancers. Among these, 34 (45.9%) were squamous cell
      carcinomas, 19 (25.7%) were adenoid cystic carcinomas, and 21 (28.4%) were of
      other histologic types. Presenting symptoms were most frequently dyspnea (55.4%),
      hemoptysis (48.6%), cough (41.9%), and hoarseness (35.1%). Most patients (77.3%)
      were former or current smokers, particularly those with squamous cell carcinoma
      (93.3%). For the entire group of 74 patients, the 5-year disease-specific
      mortality rate was 72.9% and the 5-year all-cause mortality rate was 79.3%.
      Patients who had adenoid cystic carcinoma and those with cervical primaries had
      better rates of disease-specific and overall survival than others (p = 0.036 and
      0.006 for the former patient group and p = 0.006 and 0.030 for the latter patient
      group). Among patients with incident disease treated at our institution (n = 45),
      those undergoing primary operation with adjuvant radiotherapy appeared to have
      better disease-specific and overall survival rates compared with those undergoing
      primary radiotherapy with or without chemotherapy (p = 0.0002 and 0.0003,
      respectively). Although those undergoing operation and receiving radiotherapy did
      better than those undergoing operation alone, the difference was not
      statistically significant. CONCLUSIONS: Primary tracheal cancers are very rare,
      and our results should be viewed with caution, given that our population
      comprised a small heterogeneous group treated over a 60-year period. Although
      squamous cell carcinoma was the most common pathology in smokers, adenoid cystic
      carcinoma was more prevalent among nonsmokers. Operation with adjuvant
      postoperative radiotherapy is recommended for most patients.

PMID- 16427550
TI  - Objective comparison of complications resulting from laparoscopic bariatric
      procedures.
AB  - BACKGROUND: Several surgical treatment options for morbid obesity exist.
      Currently, there are no studies that objectively compare complication rates after
      laparoscopic bariatric operations performed at a single institution. We
      objectively classify and compare complications resulting from laparoscopic
      adjustable gastric banding (LABG), Roux-en-Y gastric bypass (RYGB), and
      biliopancreatic diversion (BPD) with duodenal switch (DS). STUDY DESIGN: A
      retrospective review of a prospective database of all patients undergoing
      laparoscopic bariatric operation was performed. Complications were categorized
      according to severity score using a well-described classification system and
      compared between procedures. RESULTS: From September 2000 to July 2003, 780
      laparoscopic bariatric operations were performed: 480 LAGB, 235 RYGB, and 65
      BPD+/-DS. There was one late death. Total complication rates were: 9% for LAGB,
      23% for RYGB, and 25% for BPD+/-DS. Complications resulting in organ resection,
      irreversible deficits, and death (grades III and IV) occurred at rates of 0.2%
      for LAGB, 2% for RYGB, and 5% for BPD+/-DS. LAGB group had a statistically
      significant lower overall complication rate, both by incidence and severity, as
      compared with other groups (p < 0.001). After controlling for differences of
      admission body mass index, gender, and race, the LAGB group had an almost three
      and a half times lower likelihood of a complication compared with the RYGB group
      (odds ratio, 3.4; 95% CI, 2.2-5.3, p < 0.001) and had an over three and a half
      times lower likelihood of a complication compared with the BPD with DS group
      (odds ratio, 3.6; 95% CI, 1.8-7.1, p < 0.001). There was no statistically
      significant difference between complication rates of RYGB and BPD+/-DS.
      CONCLUSIONS: Bariatric operation complication rates range from 9% to 25%; very
      few complications are serious. Laparoscopic adjustable gastric banding is the
      safest operation in terms of complication rate and severity when compared with
      laparoscopic Roux-en-Y gastric bypass or laparoscopic malabsorptive operations.

PMID- 16427551
TI  - Diagnosis and management of partial small bowel obstruction after laparoscopic
      antecolic antegastric Roux-en-Y gastric bypass for morbid obesity.
AB  - BACKGROUND: The resultant derangement of the normal gastrointestinal anatomy
      after a gastric bypass procedure increases the incidence of, and level of
      difficulty diagnosing, partial small bowel obstruction (SBO) in morbidly obese
      patients. We evaluated the diagnostic methods for partial SBO and the clinical
      characteristics according to the time after initial operation. STUDY DESIGN: Data
      of 1,400 consecutive patients who underwent antecolic antegastric laparoscopic
      Roux-en-Y gastric bypass between 2001 and 2004 were retrospectively analyzed.
      RESULTS: Partial SBO developed in 21 (1.5%) patients after laparoscopic Roux-en-Y
      gastric bypass. Five of 15 patients were preoperatively diagnosed with SBO by a
      gastrograffin study and CT scan diagnosed 17 of 19 patients (p = 0.002). Causes
      of SBO included jejunojejunostomy stenosis (n = 6), adhesions (n = 5),
      incarcerated ventral hernia (n = 5), internal hernia (n = 3), and other (n = 2).
      The majority of patients (n = 19) underwent surgical treatment. CONCLUSIONS: The
      most frequent cause of early SBO is jejunojejunal anastomotic stenosis. CT scan
      is a more accurate diagnostic tool for detecting partial SBO, compared with use
      of a gastrograffin study. Operation remains the most appropriate and definitive
      treatment for this complication and the laparoscopic approach is a feasible and
      safe surgical treatment option.

PMID- 16427552
TI  - Economic evaluation of minimally invasive colectomy.
AB  - BACKGROUND: We performed a cost-benefit analysis of minimally invasive colectomy
      (MIC) with the appreciation that this approach extends the duration of the
      operation and requires additional instruments and equipment when compared with
      the open procedure. These negatives may be offset by decreased pain, earlier
      initiation of oral feeding, and a shorter hospitalization. STUDY DESIGN: We
      reviewed operating room records of all open colectomies (OCs) and MICs performed
      at Strong Memorial Hospital between January 1, 2000, and March 31, 2004, as
      defined by CPT codes. Operating room times, total operating room costs, lengths
      of hospital stay, and total hospital costs were calculated for each procedure.
      RESULTS: Sixty-eight right hemicolectomies (54 OCs and 14 MICs) were performed.
      Operating room time was significantly longer for MIC compared with OC (214 +/- 41
      minutes versus 170 +/- 56 minutes, p = 0.01). Length of hospital stay was shorter
      for MIC compared with OC (4.5 +/- 1.3 days versus 7.4 +/- 2.5 days, p = 0.004).
      There were 131 left hemicolectomies (104 OCs and 27 MICs) performed. Operating
      room time was significantly longer for left MIC compared with left OC (256 +/- 46
      minutes versus 213 +/- 60 minutes, p = 0.005). Length of hospital stay was
      shorter for left MIC than for left OC (4.4 +/- 1.3 days versus 7.9 +/- 3.0 days,
      p = 0.001). Total hospital costs were significantly lower for MIC compared with
      OC (8,580 US dollars +/- 1,358 US dollars versus 10,303 US dollars +/- 3,299 US
      dollars, p = 0.046). CONCLUSIONS: MIC is associated with a significantly longer
      operating room time and a shorter hospital stay than OC. Operating room cost is
      significantly higher for MIC, but total hospital cost is lower. MIC is cost
      effective and results in significant savings to the health-care system.

PMID- 16427553
TI  - Factors associated with early recurrence after resection for hepatocellular
      carcinoma and outcomes.
AB  - BACKGROUND: Early recurrence (ER) (<1 year) after liver resection is one of the
      most important factors that impact the prognosis of patients with hepatocellular
      carcinoma (HCC). We sought to determine factors associated with ER of HCC and
      examine the outcomes thereafter. STUDY DESIGN: From March 2001 to June 2003, 56
      patients underwent hepatic resection for HCC at University of Toronto and were
      prospectively followed with median followup of 24 months. Patients with ER were
      compared with those who remained disease free for more than 1 year. Patient
      characteristics, tumor stage, and operative procedures were evaluated for their
      prognostic significance by univariate and multivariable analysis. Time to
      recurrence and time to death were analyzed using Kaplan-Meier survival curves and
      compared using log-rank analysis. RESULTS: The initial procedure in all patients
      was surgical hepatectomy. ER occurred in 21 patients (38%), 31 (55%) remained
      disease free for more than 1 year, and 4 (7%) were omitted from evaluation
      because of early (<30 days) death. Median survival after initial hepatic
      resection for those with ER was 27 months, and 2-year survival was 54%. There
      were no deaths in the group that remained disease free for more than 1 year (100%
      2-year survival, p < 0.05). By multivariate analysis, vascular invasion and
      positive microscopic margins were significant predictors when all 4 variables
      were considered in the model (p < 0.05). After ER, 11 of 21 patients (52%)
      underwent additional therapy with significant improvement in median survival (33
      months) compared with those not eligible for conventional therapy (18 months, p =
      0.05). CONCLUSIONS: ER after liver resection for HCC is the leading cause of
      death during the first 2 years after potentially curative resection. ER will
      develop in approximately 75% of patients with either vascular invasion or
      positive margins. For patients with these predictive factors additional treatment
      might be advised.

PMID- 16427554
TI  - Gender and geographic influence on the racial disparity in bladder cancer
      mortality in the US.
AB  - BACKGROUND: In 2005, there were an estimated 63,210 new cases of bladder cancer
      and 13,180 related deaths in the US. African Americans reportedly have a lower
      incidence of bladder cancer, but a higher mortality. The objective of this study
      was to evaluate the gender and geographic differences in bladder cancer survival
      between Caucasians and African Americans to better understand the racial
      disparity in bladder cancer survival. STUDY DESIGN: Surveillance Epidemiology and
      End Results Program (SEER) data were used to evaluate racial differences in
      bladder cancer survival from 1973 to 1999. Bivariate and multivariate Cox
      proportional hazard models were performed to determine the relationship between
      race and survival, adjusting for cancer stage and grade, marital status, region
      of country, treatment received, and the interaction between race and region.
      RESULTS: African Americans were diagnosed with higher grade (p < 0.001) and
      higher stage (p < 0.001) tumors, compared with Caucasians. In the multivariable
      model, African-American race was an independent predictor of poor survival,
      adjusting for age, marital status, region of the country, stage, grade, treatment
      received, and interaction between race and region. Surprisingly, African
      Americans diagnosed in the Atlanta metropolitan area had a substantially worse
      survival. CONCLUSIONS: African Americans were diagnosed with more aggressive and
      more advanced tumors. Adjusted multivariable models demonstrated a survival
      advantage for Caucasians, with African-American race being an independent
      predictor of poor survival, especially when diagnosed in the Atlanta metropolitan
      area. Racial disparity continues to exist in bladder cancer presentation and
      survival in the US.

PMID- 16427555
TI  - Detailed investigation of the relationship between the inferior laryngeal nerve
      including laryngeal branches and ligament of Berry.
AB  - BACKGROUND: Studies about the anatomic relationship between the inferior
      laryngeal nerve (ILN) and the ligament of Berry are insufficient, despite
      controversy in the literature. In addition, the relationship between the
      laryngeal branches of the ILN and the ligament of Berry has not been
      investigated. STUDY DESIGN: Sixty specimens (120 sides) were examined for this
      study, including 41 male and 19 female cadavers between the ages of 40 and 89
      years at death. RESULTS: The nerve trunk or its anterior and posterior laryngeal
      branches run posterolateral to the ligament in 51 and 39 sides, respectively. The
      nerve trunk or both its laryngeal branches passed posteromedial to the ligament
      in 12 and 7 sides, respectively. In seven sides, the anterior branch of the ILN
      was located posterolateral and the posterior branch was posteromedial to the
      ligament. In three sides, the anterior (motor) branch of the ILN penetrated the
      ligament of Berry. In one right side, a nonrecurrent laryngeal nerve arose from
      the vagal nerve at the level of ligament of Berry. The nerve divided into the
      anterior and posterior laryngeal branches just above posterior surface of the
      ligament; both branches extended parallel to it. CONCLUSIONS: We have shown that
      the nerve was located not only posterolateral to the ligament but also
      posteromedial to it. Additionally, unlike other authors, we have shown that the
      anterior (motor) branch of the recurrent laryngeal nerve penetrated the ligament
      of Berry in 2.5% of 60 specimens.

PMID- 16427556
TI  - Use of the ON-Q pain management system is associated with decreased postoperative
      analgesic requirement: double blind randomized placebo pilot study.
AB  - BACKGROUND: Narcotics are routinely used to decrease postoperative pain after
      laparotomy. But they are associated with unwarranted side effects. The aim of
      this study was to assess the effectiveness of local perfusion of bupivacaine in
      decreasing narcotic consumption after midline laparotomy. STUDY DESIGN: We
      performed a prospective, randomized, double blind study involving patients who
      underwent a midline laparotomy with subsequent wound closure. Patients were
      randomized to receive a 72-hour continuous wound perfusion through the ON-Q pain
      management system (I Flow Corporation) of the local anesthetic bupivacaine (0.5%,
      study group) or 0.9% NaCl (control group). In addition, all patients received
      standardized intraoperative analgesia and postoperative morphine patient
      controlled analgesia. Total postoperative analgesic requirement, pain control,
      recovery of bowel function, and complications were recorded. RESULTS: Seventy
      patients were recruited: 35 in the study group (mean age, 55.7 years) and 35 in
      the control group (mean age, 58.8 years). There was no difference in overall
      postoperative pain scores. Patients in the study group reported earlier
      ambulation as compared with the control group. Mean (+/-SD) daily narcotic
      requirements were significantly less in the study group versus the control group
      (33.7+/-32 mg versus 60.1+/-62 mg, respectively; p=0.03). Patients in the study
      group made 50% fewer attempts to receive patient-controlled analgesia (p=0.011).
      But there was no significant difference in length of hospitalization or time to
      first bowel movement. CONCLUSIONS: This preliminary pilot study revealed that the
      ON-Q pain management system after midline laparotomy, as part of a multimodal
      approach, is an effective approach to postoperative pain control.

PMID- 16427558
TI  - Surgical lessons learned from suicide bombing attacks.

PMID- 16427557
TI  - Surgical therapy for hepatolithiasis: a Western experience.
AB  - BACKGROUND: Hepatolithiasis is very common in East Asia but infrequent in Western
      countries, and few reports have been published in European series. In East Asia,
      the association between cholangiocarcinoma and hepatolithiasis is well
      recognized, but, on the contrary, hepatolithiasis is uncommon in Europe and the
      United States, and the relationship with cholangiocarcinoma is not well
      established. The goal of this study was to analyze the perioperative and longterm
      results of surgical therapy for hepatolithiasis. STUDY DESIGN: Record review of
      22 patients was done to locate immediate (operative morbidity and mortality) and
      longterm (stone recurrence and survival) results of patients with hepatolithiasis
      who underwent surgical treatment. RESULTS: There were 19 (86.4%) hepatic
      resections and 10 (45.5%) hepatico-jejuno-anastomoses. Operative mortality was
      absent and morbidity rate was 27.3%. Right hepatectomy was predictive of
      postoperative complications at multivariate analysis (p = 0.04). One (4.5%)
      patient had an unknown associated cholangiocarcinoma at time of surgical
      intervention. Mean followup was 67.59 +/- 65.67 (range 12 to 215) months. None
      presented recurrent cholangitis during the followup period. CONCLUSIONS: Surgical
      therapy is a safe and effective management for hepatolithiasis. The possibility
      of developing cholangiocarcinoma in inveterate hepatolithiasis is real, and
      hepatic resection removes this risk.

PMID- 16427559
TI  - Do pathologic and molecular analyses of neck dissection specimens justify the
      preservation of level IV for laryngeal squamous carcinoma with clinically
      negative neck?

PMID- 16427560
TI  - Microsurgical fibular flap for treatment of avascular necrosis of the femoral
      head.

PMID- 16427561
TI  - Love in the time of spleen: a personal memoir.

PMID- 16427562
TI  - Has the 80-hour work week had an impact on voluntary attrition in general surgery
      residency programs?
AB  - BACKGROUND: This article attempts to assess the effect of the duty-hour
      limitations implemented in 2003 on voluntary withdrawal of general surgery
      residents. STUDY DESIGN: A questionnaire asked the program directors how many
      categorical general surgery residents left voluntarily in 2003 to 2004, their
      training levels, why they left, and where they went. Results were compared with
      an identical study of 2000 to 2001 and analyzed statistically using chi-square
      analysis. RESULTS: A total of 215 programs (85%) responded, compared with 206
      programs (81%) in the previous study. One hundred two programs (48%) reported
      voluntary attrition of 148 residents, compared with 110 programs (53%) and 167
      residents previously. An average of 1.5 residents per program left in programs
      that reported attrition and 0.7 residents per program in all responders, compared
      with 1.5 and 0.8 residents in the previous study. In both studies, most programs
      with attrition lost one (66% [2000 to 2001] and 65% [2003 to 2004]) or two
      residents (21% [2000 to 2001] and 27% [2003 to 2004]). Most attrition occurred at
      PGY1 (47%) and PGY2 (28%) levels; a total of 75% of all attrition occurred at
      these levels, compared with a total of 76% in the previous study. One hundred
      eleven residents (75%) entered other medical specialties, and 23 (16%)
      transferred to other general surgery programs, compared with 105 residents (63%)
      and 40 residents (24%) in the previous study. In both studies, personal issues
      and work hours/lifestyle were cited as the most common reasons for leaving. In
      each study, the net loss to general surgery (the number of residents who left
      voluntarily divided by the total resident population at risk) was 3% for that
      academic year. Analysis showed no statistically significant difference.
      CONCLUSIONS: Rates and patterns of attrition seem to have been unaffected by
      Accreditation Council for Graduate Medical Education work-hours limitations.

PMID- 16427563
TI  - Improving functional status and quality of life in elderly patients with
      peripheral arterial disease.

PMID- 16427564
TI  - Patient preference and outcomes-based surgical care among octogenarians and
      nonagenarians.

PMID- 16427565
TI  - Delayed recognition -- Larrey and Les Invalides.

PMID- 16427566
TI  - Extralobar pulmonary hamartoma.

PMID- 16427568
TI  - Triple-staple technique for low rectal anastomoses eliminates the purse-string
      suture and facilitates stapled colorectal anastomosis.

PMID- 16427567
TI  - Extrarenal angiomyolipoma originating from the right ovarian vein occluding the
      inferior vena cava and right atrium.

PMID- 16427569
TI  - Seventy-five years after the birth of an idea: a tribute to John H Gibbon Jr.

PMID- 16427570
TI  - Beheading the unicorn: an adventure in surgery.

PMID- 16427571
TI  - Subxiphoid incisional hernias after median sternotomy.

PMID- 16427573
TI  - Esophageal perforations.

PMID- 16427575
TI  - Therapy for osteoarthritis in the horse - how do we know that it works?

PMID- 16427576
TI  - Footbaths: the solution to digital dermatitis?

PMID- 16427577
TI  - BRDC and the modulation of lung inflammation.

PMID- 16427578
TI  - Atopic dermatitis in dogs - hitting the moving target.

PMID- 16427579
TI  - Amphibian decline: the urgent need for amphibian research in Europe.

PMID- 16427580
TI  - Neurodegenerative diseases in domestic animals: a comparative review.
AB  - Neurodegenerative diseases are characterised by selective damage to specific
      neurons in the nervous system. Interest in such diseases in humans has resulted
      in considerable progress in the molecular understanding of these disorders in
      recent decades. Numerous neurodegenerative diseases have also been described in
      domestic animals but relatively little molecular work has been reported. In the
      present review, we have classified neurodegenerative disease according to
      neuroanatomical criteria. We have established two large groups, based on whether
      the neuronal cell body or its axon was primarily affected. Conditions such as
      motor neuron diseases, cerebellar degenerations and neuroaxonal dystrophies are
      discussed in terms of their clinical and neuropathological features. In the most
      studied disorders, we also present what is known about underlying
      pathomechanisms, and compare them with their human counterparts. The purpose of
      this review is to re-kindle interest in this group of diseases and to encourage
      veterinary researchers to investigate molecular mechanisms by taking advantage of
      current diagnostic tools.

PMID- 16427581
TI  - Molecular genetics of sudden cardiac death in small animals - a review.
AB  - Sudden cardiac death in small animals is uncommon but often occurs due to cardiac
      conduction defects or myocardial diseases. Primary cardiac conduction defects are
      mainly caused by mutations in genes involved in impulse conduction processes
      (e.g., gap-junction genes and transcription factors) or repolarisation processes
      (e.g., ion-channel genes), whereas primary cardiomyopathies are mainly caused by
      defective force generation or force transmission due to gene mutations in either
      sarcomeric or cytoskeleton proteins. Although over 50 genes have been identified
      in humans directly or indirectly related to sudden cardiac death, no genetic
      aetiologies have been identified in small animals. Sudden cardiac deaths have
      been also reported in German Shepherds and Boxers. A better understanding of
      molecular genetic aetiologies for sudden cardiac death will be required for
      future study toward unveiling aetiology in sudden cardiac death in small animals.

PMID- 16427582
TI  - Medical treatment of osteoarthritis in the horse - a review.
AB  - The medical treatment of osteoarthritis (OA) in the horse is one of the most
      utilized therapeutic regimens in the equine practice. It is important to
      understand the anatomy of synovial joints and the pathophysiology of the disease
      process to treat OA adequately. Once a thorough understanding of the disease
      process is comprehended the proper combination of systemic nonsteroidal anti
      inflammatory drugs (NSAIDs), intraarticular steroids, viscosupplementation and
      chondroprotectants can be used to treat the disease and inhibit further
      progression of degenerative changes to the cartilage surface. The equine
      practitioner is faced with many choices for controlling inflammation in OA. This
      review presents the background and appropriate uses of various NSAIDs such as
      phenylbutazone, flunixin meglumine, ketoprofen, naproxen, and carprofen as well
      as their associated toxicities. Various steroid formulations exist for
      intraarticular (IA) administration and much has been learned in the past decade
      regarding correct dosage, frequency of administrations, indications and toxicity.
      This review presents IA steroids and their indications in addition to various
      chondroprotective drugs that also exist to control inflammation and provide
      viscosupplementation. Data are also given on disease modifying OA drugs such as
      glucosamine and chondroitin sulphate that have more recently become available to
      the equine practitioner.

PMID- 16427583
TI  - The management of bovine reproduction in elite herds.
AB  - The management of bovine reproduction is the cornerstone of health provision in
      elite herds. Aims and objectives for reproductive performance should be herd
      specific and data to monitor progress should not only be frequently collected,
      but also analysed and reported. Strategic monitoring of animals should include a
      vaginal examination for evidence of uterine disease, as well as transrectal
      ultrasonography of the genital tract. There has been considerable advancement in
      our ability to intervene in the reproduction of cattle during the last 50 years.
      However, it is salutary to note that during this time fertility has consistently
      declined, despite increasing veterinary intervention. Most elite herds use
      artificial insemination and success depends on accurate detection of oestrus
      expression, but this appears to be less overt than 25 years ago. In addition,
      half the cattle have abnormal oestrous cycles after parturition and conception
      rates are decreasing by 1% per year. Risk factors for abnormal oestrous cycles
      include puerperal problems, negative energy balance, which can be evaluated by
      body condition scoring, and uterine disease. Bacterial contamination of the
      uterus is ubiquitous after parturition in cattle and disease disrupts ovarian
      follicle growth and function. Reproduction is also disrupted by stress associated
      with clinical disease, pain or a sub-optimal environment. The challenge for
      veterinarians providing reproduction control programmes to elite herds is to
      transfer our knowledge of the problems underlying subfertility to the farm, in
      order to provide effective solutions.

PMID- 16427584
TI  - Treatment strategies for digital dermatitis for the UK.
AB  - Digital dermatitis is a worldwide disease causing lameness in cattle, especially
      when housed. Despite its widespread nature there are relatively few peer-reviewed
      articles providing experimental data concerning its treatment and control. At the
      risk of descending to anecdote, this review attempts to summarise the current
      state of knowledge. Three approaches to digital dermatitis treatment have been
      used: (1) systemic antibiotics, (2) individual topical treatment, and (3) mass
      topical therapy using a footbath. Systemic antibiotics have become a rare
      treatment because of their cost and perceived lack of efficacy. Individual
      topical treatment, mainly with antibiotic preparations, is the most commonly
      reported method. It is widely considered the treatment of choice by virtue of
      reliable information about efficacy, the advantage of precise targeting of
      antibiotic usage and the requirements of legislation. However, at least in the
      UK, mass treatment of digital dermatitis by foot bathing is commonly used on many
      farms. In some cases, for example with antibiotic footbath solutions, these
      treatments create legislative, health and safety and environmental difficulties.
      Despite the widespread use of many different treatments, there is a lack of good
      comparative data and the consequence is a very variable and somewhat anecdotal
      approach in the field. There is a pressing need for well-researched treatment
      strategies for different herd situations.

PMID- 16427585
TI  - Pre-operative and anaesthesia-related risk factors for mortality in equine colic
      cases.
AB  - Mortality rates for horses that have undergone emergency abdominal surgery are
      higher than for other procedures. Here, multivariable modelling of data from 774
      surgical colic cases is used to identify pre-operative and anaesthesia-related
      variables associated with intra- and post-operative mortality. Intra-operative
      mortality was significantly (P<0.05), and positively associated with heart rate
      and packed cell volume (PCV) at admission, and negatively associated with the
      severity of pain. Post-operative mortality increased with increasing age and PCV
      at admission. Draught horses, Thoroughbreds and Thoroughbred-cross horses carried
      a significantly worse prognosis. We detected a small but significant variability
      in the risk of intra-operative death amongst referring veterinary surgeons.
      Different anaesthetic induction agents, inhalation maintenance agents and the
      use, or not, of intermittent positive pressure ventilation had no significant
      effect on risk of death. We conclude that cardiovascular compromise, level of
      pain, age, and breed are all associated with the risk of mortality in equine
      surgical colic cases.

PMID- 16427586
TI  - Characterization of certain inflammatory variables in the peripheral blood of
      clinically healthy dogs.
AB  - Many laboratory techniques have been developed to study and quantify the
      inflammatory response, including the release of acid hydrolase enzymes,
      leukotriene B(4) (LTB(4)) production, reactive oxygen species (ROS) production
      and complement conversion studies. Although extensively studied in human health
      and disease, the relevance of such tests in the dog is largely unknown. After
      isolation of the peripheral blood mononuclear cell (PBMC) and polymorphonuclear
      cell (PMN) fractions from the peripheral blood of 38 clinically healthy dogs,
      values for ROS production were similar for both cell fractions when measured by
      luminol-enhanced chemiluminescence (17,853+/-9,695 U/10(6) cells versus 19,138+/
      14,569 U/10(6) cells for the PBMC (n=38) and PMN (n=18) fractions, respectively).
      However, the mean time taken to reach maximum chemiluminescence was noticeably
      shorter in the PBMC fraction (5.1+/-3.3 versus 10.7+/-2.5 min for PBMCs (n=36)
      and PMNs (n=18), respectively). Intracellular concentrations of beta
      glucuronidase, beta-galactosidase and N-acetyl-beta-glucosaminidase were assayed
      by spectrofluorometry. Mean values for all three enzymes were higher in PBMCs
      (n=31-35) than in PMNs (n=10-14). Both cell fractions released 20% of the
      intracellular enzyme concentration when stimulated with opsonized zymosan.
      Following incubation with A23187 (1 microM), mean LTB(4) production was higher in
      PBMCs (4.45+/-2.92 ng/10(6) cells; n=27) than in PMNs (0.96+/-2.22 ng/10(6)
      cells; n=13) using a validated high performance liquid chromatography (HPLC)
      assay. Immunoprecipitation studies revealed that the mean percentage conversion
      of C3 to C3b following stimulation with opsonized zymosan was 57.3+/-13.4%
      (n=36). The results provide normal values for clinically healthy dogs that may
      subsequently be used in future studies investigating dogs with various
      inflammatory disorders.

PMID- 16427587
TI  - Increased leukotriene B(4) production, complement C3 conversion and acid
      hydrolase enzyme concentrations in different leucocyte sub-populations of dogs
      with atopic dermatitis.
AB  - Various markers of the inflammatory response were measured in peripheral blood
      mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) from 31 dogs
      with atopic dermatitis (AD). The variables assayed included chemiluminescence,
      acid hydrolase enzyme concentrations, leukotriene B(4) (LTB(4)) production and
      complement C3 conversion. The results were compared to those derived from a
      population of clinically healthy dogs. Dogs with AD exhibited a significant
      increase in median LTB(4) production in PMNs compared to controls (0.94 versus
      0.00 ng/10(6) cells; P<0.01). Significant increases in the median concentrations
      of intracellular beta-galactosidase (PBMC fraction - 0.42 versus 0.25 mU/10(6)
      cells; P<0.05) (PMN fraction - 0.47 versus 0.12 mU/10(6) cells; P<0.01) and beta
      glucuronidase (PBMC fraction - 0.52 versus 0.27 mU/10(6) cells; P<0.05) were also
      evident in the AD group. Although median maximum chemiluminescence values for
      both leucocyte sub-populations were higher in controls, the differences recorded
      were not significant (P>0.05). However, the median time taken to reach maximum
      chemiluminescence was significantly shorter in the PMN fraction of dogs with AD
      (7.00 versus 10.00 min; P<0.01). Atopic dogs had a significant increase in the
      median percentage conversion of complement C3 to C3b (66.0 versus 57.3%; P<0.01).
      The results of this study indicate a priming of the inflammatory response in dogs
      with AD. The role of LTB(4) in the pathogenesis of canine AD and the potential
      efficacy of leukotriene antagonists in the treatment of this disorder warrant
      further investigation.

PMID- 16427588
TI  - Sensitivity of commercial prothrombin time reagents to detect coagulation factor
      deficiencies in equine plasma.
AB  - The sensitivity of commercial prothrombin time (PT) tests was assessed based on a
      dilution series of equine pooled plasma (EPP) (experiment 1) and on 40 equine
      plasma samples with reduced activity of coagulation factors II, V, VII and X
      (experiment 2). Two different PT reagents (reagent 1, human placental
      thromboplastin; reagent 2, recombinant human tissue factor) were used according
      to the manufacturers' instructions (standard test, PT([ST])) and compared to a
      modified test procedure (modified test, PT([MT])) using sample dilution and
      fibrinogen addition. In all samples, sensitivity was lower (P<0.01) when using
      PT([ST]) with reagent 2 (0.20) than when using either PT([ST]) with reagent 1
      (0.65) or PT([MT]) with both reagents (reagent 1, 0.60-0.75, reagent 2, 0.58
      0.70, depending on sample dilution). The highest sensitivity was found for
      PT([MT]) when using a 1:20 sample dilution. In those samples in which at least
      one coagulation factor activity was decreased (by 20%; n=18), the sensitivity of
      PT([ST]) with reagent 2 (0.33) was found to be inadequate, in contrast to all
      other test procedures (0.83-0.94). This low sensitivity corresponded to shorter
      time intervals between different coagulation activity levels prepared by EPP
      dilution. The results indicate that adequate sensitivity of PT measurements in
      equine plasma can be achieved using a standard test procedure as long as a
      suitable reagent is used.

PMID- 16427589
TI  - Genetic analysis of syndactyly in German Holstein cattle.
AB  - Congenital syndactyly with a variable number of affected feet was observed in
      eight black and white German Holstein calves. Analysis of the pedigree data
      revealed that all affected individuals could be traced back to a single founder.
      The pedigree was consistent with monogenic autosomal recessive inheritance and
      variable expressivity. Bovine syndactyly or "mulefoot" has been previously shown
      to map on the telomeric end of bovine chromosome 15 and we performed PCR
      genotyping of microsatellite markers spanning 27 cM of this chromosomal region to
      test the new cases for genetic linkage with the phenotype. The haplotype
      segregation confirmed the suggested inheritance pattern of the mulefoot mutation
      in this family and markers RM004, BM848 and BMS820 showed significant linkage to
      the phenotype. The results confirmed the chromosomal location of the mulefoot
      gene in this pedigree. Furthermore the study demonstrated that although marker
      testing has been available for nearly a decade the use of mulefoot carriers in
      cattle breeding remains uncontrolled. The presented family provides a resource
      for positional cloning of the causative mutation.

PMID- 16427590
TI  - Clopidogrel induced suppression of bovine platelet activation in vitro and a
      preliminary study of its effect on the development of Mannheimia haemolytica
      induced pneumonia.
AB  - We report here on the influence of the platelet antagonist clopidogrel (Plavix)
      on bovine platelet function. We first evaluated the capacity of clopidogrel to
      inhibit adenosine diphosphate (ADP)-stimulated platelet function in the bovine
      species, using an ex vivo approach with blood from treated animals. Platelets
      isolated from treated calves displayed rapid and consistent reduction in function
      (aggregation, thromboxane production) upon ADP, but not platelet activating
      factor (PAF), stimulation. We then examined the possibility that clopidogrel
      could influence Mannheimia haemolytica pneumonia pathobiology using an
      experimental challenge model. We were unable to detect significant differences
      between clopidogrel treated and untreated animals when challenged with intra
      tracheal inoculation of M. haemolytica. There was a trend towards inhibition of
      platelet degranulation in the affected regions of lungs from clopidogrel treated
      calves, and pre-treated challenged animals had similar amounts of fibrin
      deposition and enhanced fibrous tissue formation in their lungs when compared
      with control counterparts.

PMID- 16427591
TI  - Factors associated with the prevalence of osseous fragments in the limb joints of
      Hanoverian Warmblood horses.
AB  - Factors associated with the prevalence of osseous fragments (OF) in fetlock and
      hock joints were investigated in a population of young Hanoverian Warmblood
      horses selected for sale at auction from 1991 to 1998. The study was based on
      results of a standardized radiological examination of 3127 horses. The
      prevalences of OF in the two joints were significantly dependent on the date,
      type and quality of the auction, the region of origin and on the anticipated
      suitability of the horses for dressage and/or show-jumping. The probability of
      finding OF increased with wither-height. Furthermore, there was a significant
      association of the individual sire with the prevalence of OF in both fetlock and
      hock joints, and of the maternal grandsire with the prevalence of OF in the hock
      joints. Consequently, both non-genetic and genetic parameters should be taken
      into account in order to reduce the prevalence of OF in young Warmblood riding
      horses.

PMID- 16427592
TI  - Catastrophic fracture of the lateral condyle of the third metacarpus/metatarsus
      in UK racehorses - fracture descriptions and pre-existing pathology.
AB  - The characteristics of, and pre-existing pathology associated with 75 cases of
      fatal lateral condylar fracture sustained by Thoroughbreds while racing in the UK
      were described. Cases were identified from 220 cases of fatal distal limb
      fracture submitted as part of studies designed to identify risk factors for all
      fatal distal limb fractures. Fractures were most common in hurdle races and
      affected the right forelimb twice as often as the left forelimb. Fracture
      dimensions were similar to previous reports, however there was a much greater
      prevalence of articular and diaphyseal comminution and of concurrent fractures in
      the current report. Pre-existing pathology was particularly common in the medial
      and lateral parasagittal grooves of the distal articular surfaces of the third
      metacarpus/metatarsus. The degree of this pathology was not associated with horse
      age, length of career or number of career starts.

PMID- 16427593
TI  - Identification of porcine circovirus type 2 in retrospective cases of pigs
      naturally infected with porcine epidemic diarrhoea virus.
AB  - The identification of porcine circovirus type 2 (PCV2) was studied in fresh
      intestinal tissues by polymerase chain reaction (PCR) and in formalin-fixed,
      paraffin-wax-embedded intestinal tissues by in situ hybridisation. The tissues
      came from pigs naturally infected with porcine epidemic diarrhoea virus (PEDV). A
      total of 35 (32.7%) of 107 small intestinal samples from pigs naturally infected
      with PEDV were found to be positive using PCR. Positive signals for PCV2 were
      detected in 32 (29.9%) of 107 small intestinal samples from pigs naturally
      infected with PEDV by in situ hybridisation. The distribution of positive cells
      in the jejunum and ileum was multifocal or patchy. Distinct positive labelling
      was found throughout the lamina propria in the small intestines. The results of
      this study indicate that PCV2 is highly prevalent in pigs naturally infected with
      PEDV.

PMID- 16427594
TI  - The effect of speed and gradient on hyperextension of the equine carpus.
AB  - The equine carpus has a well-defined limit to joint extension at approximately
      180 degrees . During locomotion however, the carpus hyperextends during stance
      phase. Hyperextension is resisted by the carpal bones and ligaments, and it has
      been proposed that large increased hyperextension might relate to potentially
      damaging stress levels in the carpus. The aim of this study was to investigate
      the relationship between peak hyperextension of the carpus (PCE) and speed during
      locomotion on the level and on an incline. Five Thoroughbred horses were
      exercised on a treadmill at speeds between 1.8 and 10 m/s at 0% and +7.5%
      gradients. PCE was obtained using optical motion capture and linear regression
      used to describe the relationship between PCE and speed on each gradient. PCE
      increased linearly with speed during locomotion. The rate of increase was greater
      on a +7.5% gradient. The fit of the regression equations was increased
      considerably by subtracting standing carpal angle from PCE during locomotion.

PMID- 16427595
TI  - A report of mycobacteriosis caused by Mycobacterium marinum in bullfrogs (Rana
      catesbeiana).
AB  - The occurrence of mycobacteriosis caused by Mycobacterium marinum in a commercial
      breeding farm of bullfrogs (Rana catesbeiana) in Rio de Janeiro, Brazil is
      described. Ten animals presented skin lesions on the head and extremities. These
      and 38 other asymptomatic adult animals from various tanks were killed and at
      necropsy disseminated granulomatous lesions were observed in the 10 clinically
      affected animals and in 16 (42.1%) of the asymptomatic frogs. Acid-fast bacilli
      were observed in all smears of the 10 symptomatic frogs and in all but one from
      the 16 asymptomatic animals with visceral lesions. Ten samples from the 25
      positive animals were randomly selected for culture which yielded four isolates
      of fast-growing (<7 days) mycobacteria. Those purified isolates were
      characterised by biochemical traditional means as M. marinum. Identification of
      the strains was confirmed using reverse-phase high-performance liquid
      chromatography and a polymerase chain reaction (PCR) restriction enzyme analysis
      assay. It is suggested that M. marinum is an important agent of granulomatous
      disease in bullfrogs and that infected animals, even when asymptomatic, could act
      as reservoirs spreading the disease and contaminating other frogs in the farm.

PMID- 16427596
TI  - Multicentric T-cell lymphosarcoma in an alpaca.
AB  - A two-year-old female alpaca with multicentric lymphosarcoma presented because of
      progressive weakness and recumbency. The diagnosis of lymphosarcoma was based on
      the detection of immature and atypical lymphocytes in a lumbosacral CSF sample.
      Post mortem examination confirmed multicentric lymphosarcoma involving multiple
      organs. Immunophenotyping using cross reactive T- and B-cell antibodies
      characterized the tumour as a T-cell lymphosarcoma.

PMID- 16427597
TI  - Occurrence of the ear-mite Raillietia auris in cattle in Austria.
AB  - We describe here the first documented case in Austria of the cattle ear mite
      Raillietia auris in a four-year-old dairy cow. The cow was mildly depressed, and
      keratoconjunctivitis was diagnosed in both eyes with Horner's syndrome in the
      left eye. The animal showed a mild head tilt to the left and a generalized ataxia
      with a tendency to move to the right side, which became exacerbated if the animal
      was blind-folded. Head pressing to the right side, dysphagia and a dropped jaw
      were also observed. Numerous rather mobile ear mites were observed at necropsy in
      the basal part of the left ear canal. The clinical significance of the cattle ear
      mite is uncertain and the clinical signs could have been caused by listerial
      encephalitis, which was also confirmed histologically in this case.

PMID- 16427598
TI  - [Abecedary of the "Annales". Part 12].
AB  - The terms included and detailed in the present part are: gold standard, grey
      literature, heterogeneity, homogeneity, and null hypothesis.

PMID- 16427599
TI  - Restoration of native folding of single-stranded DNA sequences through reverse
      mutations: an indication of a new epigenetic mechanism.
AB  - We used in vivo (biological), in silico (computational structure prediction), and
      in vitro (model sequence folding) analyses of single-stranded DNA sequences to
      show that nucleic acid folding conservation is the selective principle behind a
      high-frequency single-nucleotide reversion observed in a three-nucleotide mutated
      motif of the Maize streak virus replication associated protein (Rep) gene. In
      silico and in vitro studies showed that the three-nucleotide mutation adversely
      affected Rep nucleic acid folding, and that the single-nucleotide reversion
      [C(601)A] restored wild-type-like folding. In vivo support came from infecting
      maize with mutant viruses: those with Rep genes containing nucleotide changes
      predicted to restore a wild-type-like fold [A(601)/G(601)] preferentially
      accumulated over those predicted to fold differently [C(601)/T(601)], which
      frequently reverted to A(601) and displaced the original population. We propose
      that the selection of native nucleic acid folding is an epigenetic effect, which
      might have broad implications in the evolution of plants and their viruses.

PMID- 16427600
TI  - Cytoplasmic localization and efflux of endogenous D-aspartate in pheochromocytoma
      12 cells.
AB  - In our previous reports [Z. Long, H. Homma, J.-A. Lee, T. Fukushima, T. Santa, T.
      Iwatsubo, R. Yamada, K. Imai, FEBS Lett. 434 (1998) 231-235; Z. Long, M. Sekine,
      M. Adachi, T. Furuchi, K. Imai, N. Nimura, H. Homma, Arch. Biochem. Biophys. 404
      (2002) 92-97], we demonstrated for the first time that D-aspartate (D-Asp) is
      actually synthesized in cultured mammalian cells such as PC12, MPT1, and GH3
      cells. After its synthesis, this unique amino acid is spontaneously and
      continuously released into the extracellular space during cell culture. In the
      current study, we characterized two different types of D-Asp efflux in PC12
      cells. One is a spontaneous and continuous form of release of cytoplasmic origin
      that does not involve exocytotic efflux of vesicular origin. Endogenous D-Asp is
      predominantly localized to the cytoplasm of cells, and this form of D-Asp release
      presents a striking contrast to exocytotic, quantal discharge of vesicular
      dopamine. The other form of efflux is also of cytoplasmic origin and occurs
      through volume-sensitive organic anion channels that are opened upon hyposmotic
      stimuli. Interestingly, this latter form of efflux is potentiated by
      acetylcholine stimulation.

PMID- 16427601
TI  - Correlation between decreased sensitivity of the Daudi lymphoma cells to VP-16
      induced apoptosis and deficiency in DNAS1L3 expression.
AB  - A functional relationship between the apoptotic endonuclease DNAS1L3 and the
      chemotherapeutic drug VP-16 was established. The lymphoma cell line, Daudi,
      exhibited a significant resistance to VP-16 treatment in comparison to the
      lymphoma/leukemia cell line, U-937. While U-937 cells degraded their DNA into
      internucleosomal fragments, Daudi cells failed to undergo such fragmentation in
      response to the drug. Activation of both caspase-3 and DNA fragmentation factor
      was not sufficient to trigger internucleosomal DNA fragmentation in Daudi cells.
      No correlation was found between expression levels of topoisomerase-II, Pgp, Bcl
      2, Bax, or Bad and decreased sensitivity of Daudi cells to VP-16. Daudi cells
      failed to express DNAS1L3 and ectopic expression of this protein significantly
      sensitized the cells to VP-16. An enhancement of caspase-3 activity and collapse
      of mitochondrial membrane potential underlie DNAS1L3-mediated sensitization of
      Daudi cells to VP-16, which may be a direct result of DNAS1L3-mediated increase
      in PARP-1-activating DNA breaks after VP-16 treatment. Our results suggest that
      DNAS1L3 plays an active role in lymphoma cell sensitization to VP-16 and that its
      deficiency may constitute a novel mechanism of drug resistance in these cells.

PMID- 16427602
TI  - Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines.
AB  - Aberrant activation of Wingless-type (Wnt) signaling pathway plays a critical
      role in oncogenesis of various human cancers. Wnt inhibitory factor-1 (WIF-1) is
      a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in
      the extracellular space. Recently, we reported Wnt signaling in various human
      malignancies. In addition, we identified in lung cancer that WIF-1 is silenced
      due to promoter hypermethylation. In this study, we found constitutive activation
      of Wnt signaling and WIF-1 silencing in nasopharyngeal carcinoma (NPC) cell
      lines. Furthermore, by utilizing methylation-specific PCR and sequence analysis,
      we demonstrated that frequent hypermethylation of the WIF-1 promoter correlates
      with WIF-1 silencing in NPC cell lines. Our results indicate that aberrant Wnt
      signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing in
      at least cell lines. Strategies targeting these molecules should be potentially
      promising in treating NPC.

PMID- 16427603
TI  - Polyglutamine expansion inhibits respiration by increasing reactive oxygen
      species in isolated mitochondria.
AB  - Huntington's disease results from expansion of the polyglutamine (PolyQ) domain
      in the huntingtin protein. Although the cellular mechanism by which pathologic
      length PolyQ protein causes neurodegeneration is unclear, mitochondria appear
      central in pathogenesis. We demonstrate in isolated mitochondria that pathologic
      length PolyQ protein directly inhibits ADP-dependent (state 3) mitochondrial
      respiration. Inhibition of mitochondrial respiration by PolyQ protein is not due
      to reduction in the activities of electron transport chain complexes,
      mitochondrial ATP synthase, or the adenine nucleotide translocase. We show that
      pathologic-length PolyQ protein increases the production of reactive oxygen
      species in isolated mitochondria. Impairment of state 3 mitochondrial respiration
      by PolyQ protein is reversed by addition of the antioxidants N-acetyl-L-cysteine
      or cytochrome c. We propose a model in which pathologic-length PolyQ protein
      directly inhibits mitochondrial function by inducing oxidative stress.

PMID- 16427604
TI  - Neuroparsin transcripts as molecular markers in the process of desert locust
      (Schistocerca gregaria) phase transition.
AB  - Desert locust swarms occasionally cause severe ecological and economic damage,
      particularly in countries of northwest Africa. However, the physiological
      mechanisms underlying locust phase transition, the switch of the solitarious to
      the gregarious phase, remain elusive. Therefore, identification of molecular
      changes linked to this phenomenon represents a primary requirement to start
      unraveling this enigma. The present paper provides novel information on phase
      related molecular markers for locust phase transition. We present a detailed
      quantitative real-time RT-PCR analysis of two distinct neuroparsin precursor
      transcripts (Scg-NPP3 and Scg-NPP4) in the brain and in abdominal tissues of
      gregarious and solitarious desert locusts (Schistocerca gregaria). Our data
      reveal different temporal changes of these transcripts in the fat body during the
      adult stage of both phases. We, hereby, present novel scientific evidence for a
      phase-dependent regulation of these particular peptide hormone encoding
      transcripts and assign them as possible molecular markers in the process of
      locust phase transition.

PMID- 16427605
TI  - Effect of DNA structural flexibility on promoter strength--molecular dynamics
      studies of E. coli promoter sequences.
AB  - To study possible correlations between promoter activity and the structural
      flexibility of the DNA helix, we have carried out unrestrained molecular dynamics
      simulations of the -10 consensus region sequence and five variants forming the 
      10 region of various Escherichia coli promoter sequences. Analyses of the
      trajectories obtained from the simulations show that the consensus sequence has a
      pattern of two structurally flexible nucleotide steps sandwiched between two
      stiff steps. In the other sequences, this pattern varies in consonance with the
      change in the sequence. The variations in the patterns show correlation with the
      promoter strength.

PMID- 16427607
TI  - Enhanced expression of urocortin in lung tissues of rats with allergic asthma.
AB  - Bronchial asthma is defined as a chronic airway inflammatory disease
      characterized by sustained activation of many inflammatory cells including mast
      cells. Urocortin (UCN) is synthesized and secreted by human mast cells and
      activated mast cells release more UCN. On the other hand, UCN can induce mast
      cell degranulation and generation of many proinflammatory factors. The purpose of
      this study was to examine the expression profile of UCN in rat lung with allergic
      asthma. Twenty-four male Sprague-Dawley rats were allocated to normal control,
      asthma model, and dexamethasone group, respectively. Animals were actively
      sensitized by subcutaneous injection of ovalbumin (OVA) and challenged by an
      aerosol of 1% OVA 2 weeks after sensitization. Both UCN mRNA and peptide were
      expressed in normal rat lungs. Rats in asthma model group developed severe
      infiltration of inflammatory cells and inflammation in airway, together with a
      significantly up-regulated expression of urocortin mRNA detected by semi
      quantitative reverse transcriptase-polymerase chain reaction and peptide measured
      both by immunohistochemistry and Western blot analysis. In contrast, treatment
      with dexamethasone resulted in markedly ameliorated airway inflammation and
      alleviated airway inflammatory cell infiltration, coupled with a significantly
      decreased urocortin expression. Regression analysis revealed a positive
      correlation between urocortin expression and the number of inflammatory cells in
      bronchoalveolar lavage fluid (P<0.01). In the present study, we first
      demonstrated that UCN was locally produced in rat lungs and expressed more
      pronouncedly in inflammatory airway of asthmatic rats. Glucocorticoid treatment
      markedly reduced the production of UCN in asthmatic lung tissues. Peripherally
      produced UCN in lung may act as a possible local autocrine and paracrine immune
      inflammatory mediator in inflammatory airway of allergic asthma rats.

PMID- 16427608
TI  - Macrophage-secreted factors induce adipocyte inflammation and insulin resistance.
AB  - Macrophage infiltration into adipose tissue increases with obesity, a condition
      associated with low-grade inflammation and insulin resistance. We investigated
      the direct effects of macrophage-secreted factors on adipocyte inflammation and
      insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by
      RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of
      several inflammation-related genes, greater nuclear factor kappa B (NF-kappaB)
      activity, and enhanced binding of U937 monocytes. All of these effects were
      prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-kappaB
      inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified
      fatty acids and this increased lipolysis was not suppressed by insulin. In
      addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in
      adipocytes. Taken together, these results indicate that macrophage-secreted
      factors induce inflammatory responses and reduce insulin responsiveness in
      adipocytes. These effects of macrophage-secreted factors on adipocytes may
      contribute significantly to the systemic inflammation and insulin resistance
      associated with obesity.

PMID- 16427606
TI  - Hypoxia dysregulates the production of adiponectin and plasminogen activator
      inhibitor-1 independent of reactive oxygen species in adipocytes.
AB  - Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating
      concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated
      with obesity-related insulin resistance and cardiovascular disease. However, the
      mechanism that mediates the aberrant production of these two adipokines in
      obesity remains poorly understood. In this study, we investigated the effects of
      hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1
      in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient
      hypoxia markedly suppressed adiponectin mRNA expression and its protein
      secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl
      glycine, a stabilizer of hypoxia-inducible factor 1alpha (HIF-1alpha), mimicked
      the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest
      elevation of ROS in adipocytes. However, ablation of intracellular ROS by
      antioxidants failed to alleviate hypoxia-induced aberrant production of
      adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen
      peroxide (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2
      treatment decreased the expression levels of peroxisome proliferator-activated
      receptor gamma (PPARgamma) and CCAAT/enhancer binding protein (C/EBPalpha), but
      had no effect on HIF-1alpha, whereas hypoxia stabilized HIF-1alpha and decreased
      expression of C/EBPalpha, but not PPARgamma. Taken together, these data suggest
      that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression
      in adipocytes via distinct signaling pathways. These effects may contribute to
      hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and
      cardiovascular diseases.

PMID- 16427609
TI  - Testatin transgenic and knockout mice exhibit normal sex-differentiation.
AB  - Testatin is identified as a member of the Cystatin family and expressed in germ
      cells and somatic cells in reproductive tissues. Testatin transcription
      detectable in males and females at 9.5 days post coitum, before sex
      differentiation, is up-regulated just after the onset of sry expression in the
      male gonads, while is down-regulated to undetectable levels in the female gonads.
      These expression patterns suggest that Testatin might have some roles in sex
      differentiation. To address Testatin function in sex-differentiation, we analyzed
      the effects of ectopic-expression in females and null-expression in males with
      testatin transgenic and knockout mice. In the transgenic females, testatin
      expression was constitutively elevated from embryonic gonad to adult ovary, and
      its expression was as high as the wild-type male gonads. However, both types of
      mice were fertile and did not exhibit detectable abnormalities. This suggests
      that the decrease of endogenous testatin in female gonad is not critical, and the
      increase of testatin in male gonad is dispensable for sex-differentiation.

PMID- 16427610
TI  - Rad51-related changes in global gene expression.
AB  - High expression of Rad51, the catalytic component in homologous recombination,
      has been reported to contribute to genomic instability. To elucidate biological
      processes related to Rad51, we performed global gene expression analysis on human
      fibrosarcoma cells induced to express variable Rad51 levels. The results indicate
      that Rad51 overexpression mediates late rather than early transcriptional
      responses. Using Gene Ontology analysis, we extracted functional annotations for
      Rad51-related changes in gene expression that were independent of general cell
      culture effects. High Rad51 levels conferred increased expression of genes
      involved in actin remodelling. These changes were accompanied by alterations in
      cell morphology. Moreover, core components of the mismatch repair (MMR) machinery
      were down-regulated in response to increased Rad51 expression. Given the role of
      MMR in the correction of DNA mismatches during replication and recombination, a
      concurrent increase in Rad51 levels and decrease in the expression of MMR genes
      could conceivably act synergistically towards genomic instability.

PMID- 16427611
TI  - G-CSF receptor-binding cyclic peptides designed with artificial amino-acid
      linkers.
AB  - Designing small molecules that mimic the receptor-binding local surface structure
      of large proteins such as cytokines or growth factors is fascinating and
      challenging. In this study, we designed cyclic peptides that reproduce the
      receptor-binding loop structures of G-CSF. We found it is important to select a
      suitable linker to join two or more discontinuous sequences and both termini of
      the peptide corresponding to the receptor-binding loop. Structural simulations
      based on the crystallographic structure of KW-2228, a stable and potent analog of
      human G-CSF, led us to choose 4-aminobenzoic acid (Abz) as a part of the linker.
      A combination of 4-Abz with beta-alanine or glycine, and disulfide bridges
      between cysteins or homocysteins, gave a structure suitable for receptor binding.
      In this structure, the side-chains of several amino acids important for the
      interactions with the receptor are protruding from one side of the peptide ring.
      This artificial peptide showed G-CSF antagonistic activity in a cell
      proliferation assay.

PMID- 16427612
TI  - Soyasaponin I decreases the expression of alpha2,3-linked sialic acid on the cell
      surface and suppresses the metastatic potential of B16F10 melanoma cells.
AB  - The transfer of sialic acids to the non-reducing terminal positions on sugar
      chains of glycoconjugates is catalyzed by sialyltransferases (STs). Increased
      sialylation is correlated with oncogenic transformation and metastatic potential.
      ST inhibitors may be potentially valuable as anti-cancer and anti-metastatic
      agents. In this study, we evaluated the effects of soyasaponin I (Ssa I), a known
      inhibitor of STs, on tumor metastasis through studying a highly metastatic cancer
      cell line B16F10. Ssa I specifically inhibited the expression of alpha2,3-linked
      sialic acids without affecting other glycans on the B16F10 cell surface. We also
      found that Ssa I decreased the migratory ability of cells, enhanced cell adhesion
      to extracellular matrix proteins. Finally, a pulmonary metastasis assay
      demonstrated that alteration of glycosylation in this way significantly reduced
      the ability of tumor cells to distribute to the lungs of mice. Collectively,
      these findings suggested that alpha2,3-linked sialic acids may play an important
      role in metastasis potential of B16F10 cells.

PMID- 16427613
TI  - A new method for detecting interactions between the senses in event-related
      potentials.
AB  - Event-related potentials (ERPs) can be used in multisensory research to determine
      the point in time when different senses start to interact, for example, the
      auditory and the visual system. For this purpose, the ERP to bimodal stimuli (AV)
      is often compared to the sum of the ERPs to auditory (A) and visual (V) stimuli:
      AV - (A + V). If the result is non-zero, this is interpreted as an indicator for
      multisensory interactions. Using this method, several studies have demonstrated
      auditory-visual interactions as early as 50 ms after stimulus onset. The
      subtraction requires that A, V, and AV do not contain common activity: This
      activity would be subtracted twice from one ERP and would, therefore, contaminate
      the result. In the present study, ERPs to unimodal, bimodal, and trimodal
      auditory, visual, and tactile stimuli (T) were recorded. We demonstrate that (T +
      TAV) - (TA + TV) is equivalent to AV - (A + V), but common activity is eliminated
      because two ERPs are subtracted from two others. With this new comparison
      technique, the first auditory-visual interaction starts around 80 ms after
      stimulus onset for the present experimental setting. It is possible to apply the
      new comparison method to other brain imaging techniques, as well, e.g. functional
      magnetic resonance imaging.

PMID- 16427614
TI  - Altered gene expression in the subdivisions of the amygdala of Fyn-deficient mice
      as revealed by laser capture microdissection and mKIAA cDNA array analysis.
AB  - Fyn-tyrosine-kinase-deficient mice exhibit increased fearfulness and display
      enhanced excitability in the amygdala. To gain insight into the molecular changes
      associated with the increased excitability of the amygdala, we used a newly
      developed cDNA array system comprising mouse KIAA cDNA clones to identify novel
      genes differentially expressed in the amygdala of fyn(-/-) and fyn(+/-) mice
      following administration of N-methyl-D-aspartate (NMDA). Laser capture
      microdissection in combination with PCR-based cDNA amplification allowed us to
      analyze gene expression in each amygdalar subdivision. The statistical
      significance of the differential expressions was tested by one-way analysis of
      variance (ANOVA) by the false discovery rate controlling approach. Among the 805
      mKIAA cDNA clones tested, only the expression level of mKIAA1577 (Zinc finger
      SWIM domain containing protein 6; gene name, Zswim6) showed statistically
      significant change in regard to the genotype and amygdalar subdivision. Namely,
      only the lowered expression of mKIAA1577 in the central nucleus of fyn(-/-) mice
      1 h after NMDA administration (2.1-fold lower relative to fyn(+/-) mice) was
      statistically significant. In situ hybridization analysis confirmed the
      downregulation of the mRNA in the central nucleus of the fyn(-/-) mice 1 h after
      NMDA administration (3.2-fold lower relative to fyn(+/-) mice). The NMDA-induced
      change in gene expression was partially blocked by the NMDA antagonist D-AP-5.
      These results suggest that Fyn deficiency was responsible for the NMDA-induced
      downregulation of a specific gene in the amygdalar central nucleus.

PMID- 16427615
TI  - The good, the bad and the neutral: electrophysiological responses to feedback
      stimuli.
AB  - The feedback error-related negativity (fERN) is a component of the event-related
      brain potential elicited in gambling and trial-and-error learning tasks by
      negative, but not positive, feedback stimuli. Here, we present the results of a
      series of five experiments that investigated the response of the fERN to the
      presentation of neutral feedback stimuli. In three of the experiments, the
      neutral feedback stimuli indicated that the participants did not receive a
      potential reward nor incur a potential penalty (i.e., they received nothing); and
      in the remaining two experiments, the neutral feedback stimuli did not convey any
      meaningful information (i.e., the participants were either successful or
      unsuccessful on those trials, but the feedback stimuli were uninformative about
      the outcomes). Across the five experiments, we found that neutral feedback
      stimuli elicited a fERN about as large as that elicited by negative feedback
      stimuli. This result is consistent with recent proposals that the evaluative
      system that produces the fERN classifies outcomes into two categories: those
      outcomes that indicate that a goal has been satisfied and those that do not.

PMID- 16427616
TI  - Interleukin-1beta enhances the angiotensin-induced expression of plasminogen
      activator inhibitor-1 through angiotensin receptor upregulation in human
      astrocytes.
AB  - Plasminogen activator inhibitor-1 (PAI-1) regulates not only fibrinolysis but
      extracellular matrix remodeling, and angiotensin II is known to play an important
      role in controlling the expression of PAI-1 in astrocytes. We have studied the
      effect of interleukin-1beta (IL-1beta), one of major cytokines also active in the
      nervous system, on the angiotensin II-induced expression of PAI-1 in human
      astrocytes. Cultures of normal human astrocytes were stimulated with IL-1beta and
      angiotensin II, and the expression of mRNAs for angiotensin II type 1 receptor
      (AT1) and PAI-1 was analyzed by reverse transcription-polymerase chain reaction
      (RT-PCR) or real-time quantitative PCR. PAI-1 protein in astrocyte-conditioned
      medium was measured by enzyme-linked immunosorbent assay (ELISA). IL-1beta
      enhanced the expression of AT1 in astrocytes in time- and concentration-dependent
      manners. After 24-h stimulation, 10 ng/ml IL-1beta and 10 nM angiotensin II
      increased the levels of PAI-1 protein in astrocyte-conditioned medium by 1.9-fold
      and 1.8-fold of the basal value, respectively. There was no synergistic effect
      when the cells were stimulated simultaneously with IL-1beta and angiotensin II.
      When the cells were stimulated, with angiotensin II, 16 h after the stimulation
      with IL-1beta, the production of PAI-1 was enhanced by 1.4-fold as compared to
      the cells stimulated only with IL-1beta. CV-11794, an AT1 antagonist, inhibited
      the enhanced PAI-1 production in response to angiotensin II. We conclude that IL
      1beta increases angiotensin II-induced PAI-1 secretion by astrocytes through the
      induction of AT1, and the enhanced secretion of PAI-1 may modulate functions of
      plasminogen activators in the nervous system.

PMID- 16427618
TI  - Spatiotemporal overlap between brain activation related to saccade preparation
      and attentional orienting.
AB  - Recent brain imaging studies provided evidence that the brain areas involved with
      attentional orienting and the preparation of saccades largely overlap, which may
      indicate that focusing attention at a specific location can be considered as an
      unexecuted saccade towards that location (i.e. the premotor theory of attention).
      Alternatively, it may be proposed that attentional orienting is simply relevant
      for preparing saccades, but the two processes may also be completely unrelated.
      In two experiments, we examined temporal activation of brain areas by measuring
      the electroencephalogram. Central cues indicated the likely side (left or right)
      at which a to-be-attended target would occur, or to which a saccade had to be
      prepared. Cue direction-related activity was determined, time-locked to cue
      onset. In addition, in our second experiment, delayed saccades had to be carried
      out, which allows to focus on processes strongly related to saccade execution. In
      nearly all tasks, an early directing attention negativity (EDAN), an anterior
      directing attention negativity (ADAN), and a late directing attention positivity
      (LDAP) were observed, time-locked to cue onset. Source analyses supported the
      view that this activity probably originates from areas within the ventral
      intraparietal sulcus (vIPS) and the frontal eye fields (FEF). The saccade-locked
      analysis also indicated that the FEF plays an important role in triggering
      saccades, but the role of vIPS appears to be minimal. The latter finding
      disfavors the premotor theory of attention, as it suggests that the relation
      between attention and action is less direct.

PMID- 16427617
TI  - A possible new role for fish retinal serotonin-N-acetyltransferase-1 (AANAT1):
      Dopamine metabolism.
AB  - Serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase, AANAT) is the
      key enzyme in the generation of melatonin rhythms in the pineal gland and retinal
      photoreceptors. Rhythmic AANAT activity drives rhythmic melatonin production in
      these tissues. Two AANATs, AANAT1 and AANAT2, are present in teleost fish
      species. Different spatial expression patterns, enzyme kinetics and substrate
      preferences suggest that they may have different functions. Enzyme activity
      assays revealed that recombinant seabream and zebrafish AANAT1s, but not AANAT2s,
      acetylate dopamine with kinetic characteristics that are similar to those for
      tryptamine acetylation. High performance liquid chromatography analysis of
      seabream retinal extracts indicated the presence of N-acetyldopamine. Time-of-day
      analysis of retinal AANAT activity and concentration of melatonin, dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC) and N-acetyldopamine revealed a daily pattern
      of retinal melatonin and N-acetyldopamine production that are correlated with
      retinal AANAT1 activity. In situ hybridization analysis of seabream retinal
      sections indicated that tyrosine hydroxylase is expressed in the inner nuclear
      layer (INL) and that AANAT1 is expressed in the outer nuclear layer (ONL) and
      INL. Together, these observations point to the possibility that dopamine is
      acetylated by retinal AANAT1 in the INL. Such novel activity of AANAT1 may
      reflect an important function in the circadian physiology of the retina.

PMID- 16427619
TI  - Indispensable role of Bcl2 in the development of the melanocyte stem cell.
AB  - Bcl2 null mice display a characteristic loss of pigmentation demonstrating the
      importance of Bcl2 in the melanocyte (Mc) lineage. It was recently reported that
      this abnormal phenotype is due to the failure of melanocyte stem cell (MSC)
      maintenance and that Bcl2 is selectively important for the survival of MSCs.
      However, in our analysis of the same mouse, we observe a reduction in melanoblast
      (Mb) number in both epidermal and follicular populations. More importantly, there
      is a complete absence of MSCs. SCF downregulation in the epidermis is concomitant
      with the dramatic reduction in Mb numbers observed in the Bcl2 null, suggesting
      that Bcl2 is indispensable for the survival of Mbs in the absence of c-Kit
      signaling. Consistently, abrogation of c-Kit signaling in Bcl2 null mice depletes
      all Mbs and Mcs, whereas continuous expression of SCF in epidermal keratinocytes
      rescues the MSCs. Our results demonstrate that Bcl2 has a general role in Mb and
      Mc survival and is essential for the emergence of MSCs. Moreover, the results
      indicate that the first wave of Mcs that provide hair pigmentation is derived
      directly from epidermal Mbs bypassing MSCs. Furthermore, a Bcl2-independent
      mechanism of action of SCF in the Mc lineage is revealed as SCF c-Kit signaling
      is functional in the absence of Bcl2.

PMID- 16427620
TI  - Endothelial nitric oxide synthase is segregated from caveolin-1 and localizes to
      the leading edge of migrating cells.
AB  - The enzyme endothelial Nitric Oxide Synthase (eNOS) is involved in key
      physiological and pathological processes, including cell motility and apoptosis.
      It is widely believed that at the cell surface eNOS is localized in caveolae,
      where caveolin-1 negatively regulates its activity, however, there are still
      uncertainties on its intracellular distribution. Here, we applied high resolution
      confocal microscopy to investigate the surface distribution of eNOS in
      transfected HeLa cells and in human umbilical vein endothelial cells (HUVEC)
      endogenously expressing the enzyme. In confluent and non-confluent HUVEC and HeLa
      cells, we failed to detect substantial colocalization between eNOS and caveolin-1
      at the cell surface. Instead, in non-confluent cells, eNOS was concentrated in
      ruffles and at the leading edge of migrating cells, colocalizing with actin
      filaments and with the raft marker ganglioside G(M1), and well segregated from
      caveolin-1, which was restricted to the posterior region of the cells. Treatments
      that disrupted microfilaments caused loss of eNOS from the cell surface and
      decreased Ca(2+)-stimulated activity, suggesting a role of the cytoskeleton in
      the localization and function of the enzyme. Our results provide a morphological
      correlate for the role of eNOS in cell migration and raise questions on the site
      of interaction between eNOS and caveolin-1.

PMID- 16427621
TI  - CpG methylation suppresses transcriptional activity of human syncytin-1 in non
      placental tissues.
AB  - Syncytin-1 is a captive envelope glycoprotein encoded by one of human endogenous
      retroviruses W. It is expressed exclusively in the placental trophoblast where it
      participates in cell-to-cell fusion during differentiation of syncytiotrophobast.
      In other tissues, however, syncytin-1 expression must be kept in check because
      inadvertent cell fusion might be dangerous for tissue organization and integrity.
      We describe here an inverse correlation between CpG methylation of syncytin-1 5'
      long terminal repeat and its expression. Hypomethylation of the syncytin-1 5'
      long terminal repeat in the placenta and in the choriocarcinoma-derived cell line
      BeWo was detected. However, other analyzed primary cells and cell lines non
      expressing syncytin-1 contain proviruses heavily methylated in this sequence. CpG
      methylation of syncytin-1 is resistant to the effect of the demethylating agent 5
      azacytidine. The inhibitory role of CpG methylation is further confirmed by
      transient transfection of in-vitro-methylated syncytin-1 promoter-driven reporter
      construct. Altogether, we conclude that CpG methylation plays a principal role in
      the transcriptional suppression of syncytin-1 in non-placental tissues, and, in
      contrast, demethylation of the syncytin-1 promoter in trophoblast is a
      prerequisite for its expression and differentiation of multinucleated
      syncytiotrophoblast.

PMID- 16427622
TI  - Contrasting role of phospholipase C-gamma1 in the expression of immediate early
      genes induced by epidermal or platelet-derived growth factors.
AB  - While significant progress has been achieved in identifying the signal
      transduction elements that operate downstream of activated receptor tyrosine
      kinases, it remains unclear how different receptors utilize these signaling
      elements to achieve a common response. This study compares the capacity of
      epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) to elicit
      the induction of immediate early gene (IEG) mRNAs in the presence or absence of
      phospholipase C-gamma1 (PLC-gamma1). The results show that while PDGF induction
      of nearly all IEG mRNAs is abrogated in plcg1 null cells, EGF induction of the
      same genes is variable in the null cells and exhibits three distinct responses.
      Five IEG mRNAs (Nup475, Cyr61, TF, Gly, TS7) are completely inducible by EGF in
      the presence or absence of PLC-gamma1, while three others (JE, KC, FIC) exhibit a
      stringent requirement for the presence of PLC-gamma1. The third type of response
      is exhibited by c-fos and COX-2. While these mRNAs are completely induced by EGF
      in the absence of PLC-gamma1, the time course of their accumulation is
      significantly delayed. No IEG was identified as completely inducible by EGF and
      PDGF in the absence of PLC-gamma1. Electrophoretic mobility shift assays (EMSA)
      demonstrate that PLC-gamma1 is necessary for nuclear extracts from PDGF-treated
      cells, but not EGF-treated cells, to interact with probes for AP-1 or NF-kappaB.

PMID- 16427623
TI  - Dissociation of ERK and Akt signaling in endothelial cell angiogenic responses to
      beta-amyloid.
AB  - Cerebrovascular deposits of beta-amyloid (Abeta) peptides are found in
      Alzheimer's disease and cerebral amyloid angiopathy with stroke or dementia.
      Dysregulations of angiogenesis, the blood-brain barrier and other critical
      endothelial cell (EC) functions have been implicated in aggravating chronic
      hypoperfusion in AD brain. We have used cultured ECs to model the effects of beta
      amyloid on the activated phosphorylation states of multifunctional
      serine/threonine kinases since these are differentially involved in the survival,
      proliferation and migration aspects of angiogenesis. Serum-starved EC cultures
      containing amyloid-beta peptides underwent a 2- to 3-fold increase in nuclear
      pyknosis. Under growth conditions with sublethal doses of beta-amyloid, loss of
      cell membrane integrity and inhibition of cell proliferation were observed. By
      contrast, cell migration was the most sensitive to Abeta since inhibition was
      significant already at 1 muM (P = 0.01, migration vs. proliferation). In previous
      work, intracellular Abeta accumulation was shown toxic to ECs and Akt function.
      Here, extracellular Abeta peptides do not alter Akt activation, resulting instead
      in proportionate decreases in the phosphorylations of the MAPKs: ERK1/2 and p38
      (starting at 1 microM). This inhibitory action occurs proximal to MEK1/2
      activation, possibly through interference with growth factor receptor coupling.
      Levels of phospho-JNK remained unchanged. Addition of PD98059, but not LY294002,
      resulted in a similar decrease in activated ERK1/2 levels and inhibition of EC
      migration. Transfection of ERK1/2 into Abeta-poisoned ECs functionally rescued
      migration. The marked effect of extracellular Abeta on the migration component of
      angiogenesis is associated with inhibition of MAPK signaling, while Akt-dependent
      cell survival appears more affected by cellular Abeta.

PMID- 16427624
TI  - HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of
      diabetic neuropathy.
AB  - A previous phase III clinical trial failed to show significant therapeutic
      benefit of repeated subcutaneous nerve growth factor (NGF) administration in the
      treatment of diabetic neuropathy. Animal studies have since shown that site
      specific viral-mediated expression of NGF in the lumbar dorsal root ganglia
      prevents peripheral nerve dysfunction associated with chemically induced
      neuropathy. Using a Herpes simplex virus expression vector, we have investigated
      the effect of localized NGF expression in a genetic mouse model of progressive
      diabetic neuropathy, the +/+ Leprdb mouse. We found that site-specific delivery
      of NGF initially delayed the appearance of hypoalgesia, assessed by the
      Hargreaves test, by 1 month and effectively attenuated this deficit for 2 months
      over the approximately 10 months normal life-span of these animals. Once the
      disease progressed into its more severe stages, NGF, although still capable of
      altering the electrophysiological profile of the sensory A- and C-fibers and
      influencing the expression of p75 and substance P in the dorsal root ganglia,
      could no longer maintain normal nociception. These data suggest that maximal
      therapeutic benefit in future NGF-based gene therapy trials will be gained from
      early applications of such viral-mediated neurotrophin delivery.

PMID- 16427625
TI  - Enriched environment after focal cortical ischemia enhances the generation of
      astroglia and NG2 positive polydendrocytes in adult rat neocortex.
AB  - Environmental enrichment (EE) alleviates sensorimotor deficits after brain
      infarcts but the cellular correlates are not well-known. This study aimed to test
      the effects of postischemic EE on neocortical cell genesis. A neocortical infarct
      was caused by distal ligation of the middle cerebral artery in adult
      spontaneously hypertensive rats, subsequently housed in standard environment or
      EE. Bromodeoxyuridine (BrdU) was administered during the first postischemic week
      to label proliferating cells and BrdU incorporation was quantified 4 weeks later
      in the periinfarct, ipsilateral medial and contralateral cortex.
      Immunohistochemistry and confocal microscopy were used to analyze co-localization
      of BrdU with neuronal (calbindin D28k, calretinin, parvalbumin, glutamic acid
      decarboxylase, tyrosine hydroxylase), astrocytic (glial fibrillary acidic
      protein, glutamine synthetase, vimentin, nestin), microglia/macrophage (CD11b/Ox
      42, CD68/ED-1), oligodendrocyte progenitor/polydendrocyte (NG2, platelet-derived
      growth factor alpha receptor) or mature oligodendrocyte (myelin basic protein)
      markers. BrdU positive cells were increased in all analyzed cortical regions in
      stroke EE rats compared with stroke standard environment rats. Newly born cells
      in the periinfarct cortex were mostly reactive astroglia. Occasionally, BrdU
      positive cells in the periinfarct cortex that were negative for glial or
      microglia/macrophage markers co-expressed markers typical for interneurons but
      did not express appropriate functional markers. The majority of BrdU positive
      cells in intact cortical regions, ipsi- and contralaterally, were identified as
      NG2 positive polydendrocytes. Perineuronally situated newly born cells and
      polydendrocytes were found to be brain-derived neurotrophic factor
      immunoreactive. In conclusion, EE enhanced newborn glial scar astroglia and NG2+
      polydendrocytes in the postischemic neocortex which might be beneficial for brain
      repair and poststroke plasticity.

PMID- 16427628
TI  - A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating
      tyrosine kinase activities.
AB  - The cysteine in the M/IXXCW motif is conserved in all but one (threonine in place
      of cysteine) of the human protein tyrosine kinases (PTKs). We showed that all RET
      PTC-1 mutants in which the C in this motif (C376) was replaced with glycine,
      lysine, threonine or serine lost their activity in vitro. However, the C376T/S
      mutants showed normal tyrosine phosphorylation in vivo (in cells). Further
      analyses reveled that protein kinase C (PKC) initiated the activities of the
      C376T/S mutants in cells. We conclude that the M/IXXCW motif-mediated mechanisms
      which initiate PTK activities are partially replaced by a PKC-mediated mechanism.

PMID- 16427626
TI  - A dynein mutation attenuates motor neuron degeneration in SOD1(G93A) mice.
AB  - Cu/Zn SOD1(G93A) transgenic mice develop phenotypical hallmarks of ALS and serve
      therefore as an established model to study the molecular mechanisms underlying
      this disease. Recent reports demonstrate that mutations in the motor protein
      dynein in Legs at odd angles (Loa) and Cramping (Cra1) mice lead to similar but
      milder phenotypes. Surprisingly, double transgenic mice (Loa/SOD1(G93A)) have
      been recently shown to attenuate rather than to accelerate the phenotypical
      expression of motor neuron degeneration. These results raise the question whether
      other functional relevant mutations in dynein cause a similar effect. To address
      this question, we have cross-bred SOD1(G93A) with Cra1/+ mice. These double
      transgenic mice show an attenuated decline of both motor activity and body weight
      and an increase of survival time compared to SOD1(G93A) mice. Thus, this study
      confirms that mechanisms associated with dynein such as retrograde axonal
      transport may play an important role in SOD1(G93A-) toxicity on motor neurons.

PMID- 16427629
TI  - The role of Glu196 in the environment around the substrate binding site of
      leucine aminopeptidase from Streptomyces griseus.
AB  - To investigate the role of Glu196 of leucine aminopeptidase from Streptomyces
      griseus (SGAP) in SGAP activation by calcium and substrate specificity, we
      constructed E196X SGAP by saturation mutagenesis. Most mutations led to the
      abrogation of SGAP activation by calcium, and substitution with Lys led to a
      marked increase in activity toward Asp-p-nitroanilide (pNA) and a decrease in
      that toward Lys-pNA. A similar result was obtained from the investigation using
      non-calcium-activated enzyme from Streptomyces septatus (SSAP). These results
      indicate that Glu196 of SGAP is associated with the environment around the
      substrate binding site besides its role in SGAP activation by calcium.

PMID- 16427630
TI  - The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dependent apoptosis.
AB  - Recently, it has been shown that really interesting new gene (RING)-in between
      ring finger (IBR)-RING domain-containing proteins, such as Parkin and Parc, are
      E3 ubiquitin ligases and are involved in regulation of apoptosis. In this report,
      we show that p53-inducible RING-finger protein (p53RFP), a p53-inducible E3
      ubiquitin ligase, induces p53-dependent but caspase-independent apoptosis. p53RFP
      contains an N-terminal RING-IBR-RING domain and an uncharacterized, evolutionally
      highly conserved C-terminal domain. p53RFP interacts with E2 ubiquitin
      conjugating enzymes UbcH7 and UbcH8 but not with UbcH5, and this interaction is
      mediated through the RING-IBR-RING domain of p53RFP. Interestingly, the conserved
      C-terminal domain of p53RFP is required and sufficient for p53RFP-mediated
      apoptosis, suggesting p53RFP-mediated apoptosis does not require its E3 ubiquitin
      ligase activity. Together with a recent report showing that p53RFP is involved in
      ubiquitination and degradation of p21, a p53 downstream protein promoting growth
      arrest and antagonizing apoptosis, our findings suggest that p53RFP is involved
      in switching a cell from p53-mediated growth arrest to apoptosis.

PMID- 16427631
TI  - High-throughput screening of cell death inducible short peptides from TNF-related
      apoptosis-inducing ligand sequence.
AB  - Therapeutic peptides and small molecules, rationally designed to trigger cell
      death have attracted strong attention. Cell death inducible peptides were
      screened from amino acid sequence of tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). Using Fmoc solid phase synthesis, cellulose membrane
      bound octameric peptide library of TRAIL scan was prepared and cell viability
      assay was directly performed on peptide disk with Jurkat cells. Six peptide
      sequences that could induce cell death were found. Peptide sequence with RNSCWSKD
      (TRAIL(227-234)) that exist in the zinc-binding site revealed high cell death
      inducible activity. Apoptotic cell death was observed when cells were treated
      with soluble synthesized peptide.

PMID- 16427632
TI  - A WNK kinase binds and phosphorylates V-ATPase subunit C.
AB  - WNK (with no lysine (K)) protein kinases are found in many eukaryotes and share a
      unique active site. Here, we report that a member of the Arabidopsis WNK family
      (AtWNK8) interacts with subunit C of the vacuolar H+-ATPase (V-ATPase) via a
      short C-terminal domain. AtWNK8 is shown to autophosphorylate intermolecularly
      and to phosphorylate Arabidopsis subunit C (AtVHA-C) at multiple sites as
      determined by MALDI-TOF MS analysis. Furthermore, we show that AtVHA-C and other
      V-ATPase subunits are phosphorylated when V1-complexes are used as substrates for
      AtWNK8. Taken together, our results provide evidence that V-ATPases are potential
      targets of WNK kinases and their associated signaling pathways.

PMID- 16427633
TI  - Differential mechanisms of glutamate receptor regulation of SynGAP in cortical
      neurones.
AB  - One prime candidate linking N-methyl-D-aspartate (NMDA) receptors to the
      regulation of the MAP kinase cascade is SynGAP, a negative regulator of Ras. In
      order to assess how a physiological stimulus can alter SynGAP activity, an
      appropriate whole cell system must be used and SynGAP must be specifically
      extracted from membranes whilst preserving the catalytic activity of the protein.
      Here, we have achieved this and studied the effect of NMDA/alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid (AMPA) and kainate receptor stimulations on
      SynGAP activity in cortical neurones. Furthermore, we have examined the role of
      extracellular Ca2+, CaM kinase II and the PSD-95-NR2B subunit interaction in
      SynGAP activity regulation and propose a novel convergence of signalling between
      AMPA, kainate and NMDA receptors.

PMID- 16427634
TI  - Salting-in the microbial cytoplasm.
AB  - Microbial organisms are known to rely for osmotic regulatory purposes on an
      assortment of low molecular weight molecules earmarked for function as osmolytes.
      The so-called 'compatible' subclass of osmolyte, notably glycine betaine, is
      distinguished by a propensity to avoid the large bound fraction of cytoplasmic
      water adsorbed at the surface of biological macromolecules. Here we argue that
      this property is implicated in thermodynamic stabilisation of the cytoplasm. A
      rudimentary molecular statistical approach indicates that flooding the cytoplasm
      with large amounts of compatible osmolyte is an effective way to deal with the
      threat of phase separation.

PMID- 16427635
TI  - Kidney claudin-19: localization in distal tubules and collecting ducts and
      dysregulation in polycystic renal disease.
AB  - Tight junction (TJ) constitutes the barrier by controlling the passage of ions
      and molecules via paracellular pathway and the movement of proteins and lipids
      between apical and basolateral domains of the plasma membrane. Claudins,
      occludin, and junctional adhesion molecules are the major three transmembrane
      proteins at TJ. This study focuses a newly identified mammalian TJ gene, claudin
      19, in kidneys. Mouse claudin-19 composes of 224 amino acids and shares 98.2% and
      95% amino acid homology with rat and human, respectively; the most evolutionary
      related claudins are claudin-1 and -7, which share approximately 75% DNA sequence
      homology with claudin-19. Claudin-19 is abundantly expressed in the mouse and rat
      kidneys among the organs examined by Northern blots, and to a much less extent,
      also found in brain by RT-PCR. Claudin-19 and zonula occludens-1 (ZO-1) are
      localized at junctional regions of Madin-Darby canine kidney (MDCK) cells by
      immunofluorescent microscopy. In addition, ZO-1 is found in the claudin-19
      associated protein complexes in MDCK cells by co-immunoprecipitation. Using
      aquaporin-1 and aquaporin-2 antibodies as markers for different renal segment,
      strong expression of claudin-19 was observed in distal tubules of the cortex as
      well as in the collecting ducts of the medulla. To less extent, claudin-19 is
      also present in the proximal tubules (cortex) and in the loop of Henle (medulla).
      Furthermore, intense claudin-19 immunoreactivity is found co-localized with the
      ZO-1 in kidneys from postnatal day 15, day 45, and adult rats and mice. Similar
      localizations of claudin-19 and ZO-1 are also observed in human kidneys. Since
      these renal segments are mainly for controlling the paracellular cation
      transport, it is suggested that claudin-19 may participate in these processes. In
      human polycystic kidneys, decreased expression and dyslocalization of claudin-19
      are noticed, suggesting a possible correlation between claudin-19 and renal
      disorders. Taken together, claudin-19 is a claudin isoform that is highly and
      specifically expressed in renal tubules with a putative role in TJ homeostasis in
      renal physiology.

PMID- 16427638
TI  - Extremity vascular trauma in civilian population: a 7-year review from North
      India.

PMID- 16427636
TI  - Human RELMbeta is a mitogenic factor in lung cells and induced in hypoxia.
AB  - RELMbeta (resistin-like molecule) represents the most related human homologue of
      mouse RELMalpha, also known as hypoxic-induced mitogenic factor (HIMF). In this
      study, we isolated RELMbeta cDNA from human lung tissue and performed regulatory
      and functional expression studies. RELMbeta mRNA was upregulated in hypoxia in
      human lung A549 cell line as well as primary cultured adventitial fibroblasts and
      smooth muscle cells (SMC) of pulmonary arteries. Upon transfection of a RELMbeta
      encoding expression plasmid into these cells, we observed significant induction
      of proliferation particularly in SMC and A549 cells, which could be blocked by
      phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin. The
      results suggest that human RELMbeta may contribute to hypoxic-induced pulmonary
      vascular remodeling processes or hypoxia related fibrotic lung disease.

PMID- 16427639
TI  - Staged management and outcome of combined pelvic and liver trauma. An
      international experience of the deadly duo.
AB  - Pelvic fracture associated with liver trauma is not an uncommon injury
      combination in multiple trauma and is associated with high morbidity and
      mortality. The aim of this study was to examine the characteristics of this
      specific patient group, to describe the diagnostic and treatment protocols and
      finally to analyse risk factors associated with mortality. Data were collected
      over a 6-year period, ending in 2001. The pelvic injury was graded according to
      the Tile classification system and the hepatic injury was scored using the organ
      injury scale (OIS). Treatment protocol, associated injuries, complications,
      length of ICU/Hospital stay and mortality were recorded and analysed. A total of
      140 patients (40% female) with a mean age of 35.1+/-15.9 years and a median ISS
      of 41 were included in this study. The overall mortality rate was 40.7%. Binomial
      logistic regression analysis revealed age, initial blood pressure, transfusion
      requirement as well as the severity of head, chest, spleen and liver injury as
      independent parameters predicting reduced survival rates. This deadly duo of
      injuries presents a challenge to the trauma surgeon. Rapid assessment and
      treatment is required to prevent death by haemorrhage. The presence of
      concomitant injuries renders the patient very sensitive to ongoing or additional
      physiological disturbance. The principles of 'damage control surgery' must be
      applied to avoid complications such as acute respiratory distress syndrome (ARDS)
      and multiple organ dysfunction syndrome (MODS).

PMID- 16427640
TI  - Cardiopulmonary resuscitation after traumatic cardiac arrest is not always
      futile.
AB  - INTRODUCTION: The use of guidelines regarding the termination or withholding of
      cardiopulmonary resuscitation (CPR) in traumatic cardiac arrest patients remains
      controversial. This study aimed to describe the outcomes for victims of
      penetrating and blunt trauma who received prehospital CPR. METHODS: We conducted
      a retrospective review of a statewide major trauma registry using data from 2001
      to 2004. Subjects suffered penetrating or blunt trauma, received CPR in the field
      by paramedics and were transported to hospital. Demographics, vital signs, injury
      severity, prehospital time, length of stay and mortality data were collected and
      analysed. RESULTS: Eighty-nine patients met inclusion criteria. Eighty percent of
      these were blunt trauma victims, with a mortality rate of 97%, while penetrating
      trauma patients had a mortality rate of 89%. The overall mortality rate was 95%.
      Sixty-six percent of patients had a length of stay of less than 1 day. Four
      patients survived to discharge, of which two were penetrating and two were blunt
      injuries. Hypoxia and electrical injury were probable associated causes of two
      cardiac arrests seen in survivors of blunt injury. CONCLUSIONS: While only a
      small number of penetrating and blunt trauma patients receiving CPR survived to
      discharge, this therapy is not always futile. Prehospital emergency personnel
      need to be aware of possible hypoxic and electrical causes for cardiac arrest
      appearing in combination with traumatic injuries.

PMID- 16427641
TI  - The Manchester operation for uterine prolapse.
AB  - OBJECTIVE: To evaluate the clinical characteristics, complications, and
      satisfaction scores of patients who underwent the Manchester operation. METHODS:
      This retrospective observational study evaluated data from 204 women who
      underwent the Manchester operation at the Department of Obstetrics and Gynecology
      of Hacettepe University School of Medicine, Ankara, Turkey, from January 1985 to
      April 2004. RESULTS: Mean age was 34.68+/-4.24 years and parity 2.47+/-0.96;
      85.8% of the patients were premenopausal; 176 patients (86.28%) had grade 3 and
      28 (13.72%) had grade 2 uterine prolapse; 95.1% of the patients had associated
      cystoceles and 51.3% had associated rectoceles; and 81.4% had urinary
      incontinence. Regarding early postoperative complications, 27 patients (13.23%)
      had febrile morbidity; retroperitoneal hematoma occurred in 1 patient (0.49%);
      urinary retention occurred in 45 patients (22.05%), and cervical stenosis
      occurred in 23 patients (11.27%). At 1 year, 1 patient had undergone abdominal
      hysterectomy because of unsuccessful cervical dilatation; and a mean of 3.6 years
      following the operation, 8 patients (3.9%) had undergone the tension-free vaginal
      tape procedure plus a vaginal hysterectomy for recurrent stress urinary
      incontinence and uterine prolapse. The mean satisfaction/acceptance score for the
      operation was 8.52+/-2.13 (range, 2-10). CONCLUSION: A high degree of
      acceptance/satisfaction and a low morbidity rate show the Manchester operation to
      be a good option for the treatment of uterine prolapse in women who wish to keep
      their uterus.

PMID- 16427642
TI  - Why are we still promoting breast self-examination?

PMID- 16427643
TI  - Paradoxical increase in lumen size during progression of coronary
      atherosclerosis: observations from the REVERSAL trial.
AB  - Relative changes in lumen size during progression and regression of coronary
      atherosclerosis remain largely unknown. We assessed these changes using serial
      intravascular ultrasound (IVUS). From the baseline IVUS interrogations of the
      Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, 210
      focal coronary lesions with <50% angiographic stenosis were identified. Lesions
      were matched to the follow-up IVUS, performed after 18 months of treatment with
      atorvastatin 80 mg/day or pravastatin 40 mg/day. Changes in external elastic
      membrane (EEM) and lumen areas of lesions demonstrating progression and
      regression (i.e. increased and decreased atheroma area) were examined. In
      progressors (n=128), there was 1.34 mm(2) increase in EEM area for every 1mm(2)
      increase in atheroma area (r=0.72, p<0.0001). This resulted in 0.34 mm(2)
      increase in lumen area for every 1mm(2) increase in atheroma area (r=0.25,
      p=0.004). In contrast, there was no significant change in lumen area with
      regression of disease (n=82, r=-0.06, p=0.59). Progression of coronary
      atherosclerosis can be associated with a paradoxical increase in lumen cross
      sectional area, whereas regression is not associated with any change in lumen
      area. Measurement of changes in lumen size may not be an accurate method to study
      progression and regression of atherosclerotic lesions with <50% stenosis.

PMID- 16427645
TI  - The use of sparse CT datasets for auto-generating accurate FE models of the femur
      and pelvis.
AB  - The finite element (FE) method when coupled with computed tomography (CT) is a
      powerful tool in orthopaedic biomechanics. However, substantial data is required
      for patient-specific modelling. Here we present a new method for generating a FE
      model with a minimum amount of patient data. Our method uses high order cubic
      Hermite basis functions for mesh generation and least-square fits the mesh to the
      dataset. We have tested our method on seven patient data sets obtained from CT
      assisted osteodensitometry of the proximal femur. Using only 12 CT slices we
      generated smooth and accurate meshes of the proximal femur with a geometric root
      mean square (RMS) error of less than 1 mm and peak errors less than 8 mm. To
      model the complex geometry of the pelvis we developed a hybrid method which
      supplements sparse patient data with data from the visible human data set. We
      tested this method on three patient data sets, generating FE meshes of the pelvis
      using only 10 CT slices with an overall RMS error less than 3 mm. Although we
      have peak errors about 12 mm in these meshes, they occur relatively far from the
      region of interest (the acetabulum) and will have minimal effects on the
      performance of the model. Considering that linear meshes usually require about 70
      100 pelvic CT slices (in axial mode) to generate FE models, our method has
      brought a significant data reduction to the automatic mesh generation step. The
      method, that is fully automated except for a semi-automatic bone/tissue boundary
      extraction part, will bring the benefits of FE methods to the clinical
      environment with much reduced radiation risks and data requirement.

PMID- 16427644
TI  - Endothelial nitric oxide synthase haplotypes affect the susceptibility to
      hypertension in patients with type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) and hypertension (HT) commonly coexist. While
      endothelial nitric oxide synthase (eNOS) haplotypes have been associated with HT,
      it is unknown whether eNOS genotypes/haplotypes are associated with altered
      susceptibility to HT in patients with T2DM. We studied the distribution of three
      eNOS genetic polymorphisms: a single nucleotide polymorphism in the promoter
      region (T(-786)C), in exon 7 (Glu298Asp), and a variable number of tandem repeats
      in intron 4(b/a). Genotypes were determined for 102 healthy controls, 119
      patients with HT, 66 patients with T2DM, and 113 patients with T2DM+HT. In
      addition, we also compared the distribution of eNOS haplotypes in the four groups
      of subjects. No differences were found in genotype and allele distribution among
      the four groups. Conversely, the haplotypes "C Glu b" and "C Asp b" were,
      respectively, more and less common in healthy controls than in HT or in T2DM+HT
      groups (24% versus 6% and 5%, respectively; both P<0.00625; and 8% versus 18% and
      18%, respectively; both P<0.00625). Moreover, DM patients presented an overall
      distribution of eNOS haplotypes that was not different from healthy controls
      (P>0.05). Additionally, the haplotypes "C Glu b" and "C Asp b" were,
      respectively, more and less common in T2DM group than in T2DM+HT group (19%
      versus 5%; and 7% versus 18%, respectively; both P<0.00625). Our findings suggest
      a protective effect for eNOS haplotype "C Glu b" against the development of
      hypertension, and that haplotype "C Asp b" increases the susceptibility to
      hypertension in patients without or with T2DM.

PMID- 16427646
TI  - Automated determination of ethyl carbamate in stone-fruit spirits using headspace
      solid-phase microextraction and gas chromatography-tandem mass spectrometry.
AB  - A fully automated procedure using headspace solid-phase microextraction (HS-SPME)
      followed by gas chromatographic/tandem mass spectrometric (GC/MS/MS) detection
      was developed for the determination of the toxic contaminant ethyl carbamate (EC)
      in stone-fruit spirits. After addition of deuterated internal standard, the
      optimised HS-SPME extraction with carbowax/divinylbenzene fibres (30 min at 70
      degrees C) was done applying salting out with sodium chloride in the presence of
      pH 7 buffer solution. For quantitative analysis the characteristic fragmentations
      of m/z 74>44 and m/z 62>44 for ethyl carbamate as well as m/z 64>44 for ethyl
      carbamate-d5 were monitored in the multiple reaction monitoring (MRM) mode using
      a triple quadrupole instrument. In the validation studies, ethyl carbamate
      exhibited good linearity with a regression coefficient of 0.998. The limits of
      detection and quantitation were 0.03 and 0.11 mg/l. The precision never exceeded
      4.3% (intraday) and 8.2% (interday) at any of the concentrations examined. A good
      agreement of analysis results in comparison to conventional sample clean-up over
      diatomaceous earth columns was found (R = 0.956, Bias = 0.08 mg/l). The new HS
      SPME/GC/MS/MS procedure is suitable for the fast, reliable and inexpensive
      determination of ethyl carbamate in alcoholic beverages in an automated, and
      therefore, convenient procedure.

PMID- 16427647
TI  - Automated dynamic headspace organic solvent film microextraction for benzene,
      toluene, ethylbenzene and xylene. Renewable liquid film as a sampler by a
      programmable motor.
AB  - A simple, fast and efficient dynamic headspace-organic solvent film
      microextraction (DHS-OSFME) method using a new automatic device was developed.
      The renewable organic films were formed inside a microsyringe barrel using the
      uniform and repeated movement of the syringe plunger enabled by programmable
      stirring motor. The plunger speed, number of extraction cycles, and dwell time
      (stop time after each half round) were controlled by a computer software, which
      was written by C++ Builder. A theoretical treatment of the DHS-OSFME based on the
      consecutive first-order process is proposed in this report. A mathematical
      solution for the dynamic process of the mass transfer was obtained by correlating
      the variation of analyte concentration in the syringe volume with the plunger
      speed and the amount of analyte extracted to the OSF. Benzene, toluene,
      ethylbenzene, and o-xylene (BTEX) were employed as model compounds to assess the
      extraction procedure and were determined by gas chromatography-flame ionization
      detection. Of the three organic solvents (1-octanol, benzyl alcohol and n
      dodecane) studied as extractants, n-dodecane proved to be the most sensitive
      solvent for the extraction of these analytes. Several parameters, including the
      syringe withdrawal rate, dwelling time, number of extraction cycles, sampling
      volume, sample temperature, and ionic strength of the solution, were investigated
      for their effects on the extraction performance. The calibration graphs were
      linear in the range of 0.5-200 ng ml(-1), with the detection limits between 0.18
      and 0.35 ng ml(-1). Wastewater samples were extracted by the optimized method,
      and determined using the standard addition method.

PMID- 16427648
TI  - Influence of dispersing medium on grafting of aminopropyltriethoxysilane in
      swelling clay materials.
AB  - Functionalization of montmorillonite clay has been done using 3
      aminopropyltriethoxysilane in the presence of various solvent media. Qualitative
      evidence of the presence of aminosilane attached to the clay platelets have been
      identified using Fourier transform infrared spectroscopy (FTIR) and 29Si and 13C
      solid-state nuclear magnetic resonance (NMR) spectroscopy. Grafting yield has
      been calculated using thermogravimetric analysis and total grafting yield
      increases with the solvent surface energy. X-ray diffraction studies of the
      silane functionalized montmorillonite clay exhibits two peaks, which may be
      attributed to intercalation and surface interaction with the broken edge
      platelets. Functionalized clay has been characterized by surface area
      measurements to understand the influence of solvents on the surface area of the
      functionalized clay.

PMID- 16427649
TI  - Increased phospholamban phosphorylation limits the force-frequency response in
      the MLP-/- mouse with heart failure.
AB  - Reduced Ca(2+) release from the sarcoplasmic reticulum (SR) and a negative force
      frequency relation characterize end-stage human heart failure. The MLP(-/-) mouse
      with dilated cardiomyopathy is used as a model to explore novel therapeutic
      interventions but the alterations in Ca(2+) handling in MLP(-/-) remain
      incompletely understood. We studied [Ca(2+)](i) in left ventricular myocytes from
      MLP(-/-) and WT mice (3-4 months old; whole-cell voltage clamp, 30 degrees C). At
      1 Hz stimulation, the amplitude of [Ca(2+)](i) transients was similar. However,
      in contrast to WT, at higher frequencies the [Ca(2+)](i) transient amplitude
      declined in MLP(-/-) and there was no increase in SR Ca(2+) content.
      Unexpectedly, the decline of [Ca(2+)](i) was faster in MLP(-/-) than in WT (at 1
      Hz, tau of 80 +/- 9 vs. 174 +/- 29 ms, P < 0.001) and the frequency-dependent
      acceleration of the decline was abolished suggesting an enhanced basal SERCA
      activity. Indeed, the Ca(2+) affinity of SR Ca(2+) uptake in homogenates was
      higher in MLP(-/-), with the maximal uptake rate similar to WT. Phosphorylation
      of phospholamban in MLP(-/-) was increased (2.3-fold at Ser(16) and 2.9-fold at
      the Thr(17) site, P < 0.001) with similar SERCA and total phospholamban protein
      levels. On increasing stimulation frequency to 4 Hz, WT, but not MLP(-/-),
      myocytes had a net gain of Ca(2+), suggesting inadequate Ca(2+) sequestration in
      MLP(-/-). In conclusion, increased baseline phosphorylation of phospholamban in
      MLP(-/-) leads to a reduced reserve for frequency-dependent increase of Ca(2+)
      release. This represents a novel paradigm for altered Ca(2+) handling in heart
      failure, underscoring the importance of phosphorylation pathways.

PMID- 16427650
TI  - 17-beta-Estradiol decreases p38 MAPK-mediated myocardial inflammation and
      dysfunction following acute ischemia.
AB  - Understanding the inflammatory response to myocardial ischemia is an important
      part of achieving the elusive clinical goal of perfect myocardial protection.
      While it is established that estrogen affects the chronic inflammatory processes
      of coronary atherosclerosis, the effects of estrogen on acute myocardial
      proinflammatory signaling are unknown. To study this, myocardial ischemia and
      reperfusion was performed in rat hearts from normal adult males, normal adult
      females, ovariectomized (OVX) females, males supplemented with E2, and OVX
      females supplemented with E2. Following reperfusion, homogenized hearts were
      analyzed for TNF-alpha, IL-1beta, and IL-6 gene and protein expression, p38 MAPK
      activation, and the apoptosis-related proteins caspase-3 and Bcl-2. Hearts from
      proestrus females demonstrated significantly better post-ischemic functional
      recovery than males. E2 supplementation to males and OVX females improved post
      ischemic myocardial functional recovery, reduced the production of TNF-alpha, IL
      1beta and IL-6, and decreased the activation of p38 MAPK and caspase-3 when
      compared to their untreated counterparts. These results suggest that the effect
      of estrogen on cardioprotection against myocardial I/R may be attributed to its
      anti-inflammatory and anti-apoptotic properties. Further understanding of these
      mechanisms may allow therapeutic manipulation of sex hormones in the treatment of
      acute ischemic injury.

PMID- 16427651
TI  - GroEL walks the fine line: the subtle balance of substrate and co-chaperonin
      binding by GroEL. A combinatorial investigation by design, selection and
      screening.
AB  - While support in protein folding by molecular chaperones is extremely efficient
      for endogenous polypeptides, it often fails for recombinant proteins in a
      bacterial host, thus constituting a major hurdle for protein research and
      biotechnology. To understand the reasons for this difference and to answer the
      question of whether it is feasible to design tailor-made chaperones, we
      investigated one of the most prominent bacterial chaperones, the GroEL/ES ring
      complex. On the basis of structural data, we designed and constructed a
      combinatorial GroEL library, where the substrate-binding site was randomized.
      Screening and selection experiments with this library demonstrated that substrate
      binding and release is supported by many variants, but the majority of the
      library members failed to assist in chaperonin-mediated protein folding under
      conditions where spontaneous folding is suppressed. These findings revealed a
      conflict between binding of substrate and binding of the co-chaperonin GroES. As
      a consequence, the window of mutational freedom in that region of GroEL is very
      small. In screening experiments, we could identify GroEL variants slightly
      improved for a given substrate, which were still promiscuous. As the substrate
      binding site of the GroEL molecule overlaps strongly with the site of cofactor
      binding, the outcome of our experiments suggests that maintenance of cofactor
      binding affinity is more critical for chaperonin-mediated protein folding than
      energetically optimized substrate recognition.

PMID- 16427652
TI  - Nanopore-protein interactions dramatically alter stability and yield of the
      native state in restricted spaces.
AB  - We have studied the stability and the yield of the folded WW domains in a
      spherical nanopore to provide insights into the changes in the folding
      characteristics due to interactions of the polypeptide (SP) with the walls of the
      pore. Using different models for the interactions between the nanopore and the
      polypeptide chain we have obtained results that are relevant to a broad range of
      experiments. (a) In the temperature and the strength of the SP-pore interaction
      plane (lambda), there are four "phases," namely, the unfolded state, the native
      state, the molten globule phase (MG), and the surface interaction-stabilized
      (SIS) state. The MG and SIS states are populated at moderate and large values of
      lambda, respectively. For a fixed pore size, the folding rates vary non
      monotonically as lambda is varied with a maximum at lambda approximately 1 at
      which the SP-nanopore interaction is comparable to the stability of the native
      state. At large lambda values, the WW domain is kinetically trapped in the SIS
      states. Using multiple sequence alignment, we conclude that similar folding
      mechanism should be observed in other WW domains as well. (b) To mimic the
      changes in the nature of the allosterically driven SP-GroEL interactions we
      consider two models for the dynamic Anfinsen cage (DAC). In DAC1, the SP-cavity
      interaction cycles between hydrophobic (lambda>0) and hydrophilic (lambda=0) with
      a period tau. The yield of the native state is a maximum for an optimum value of
      tau=tau(OPT). At tau=tau(OPT), the largest yield of the native state is obtained
      when tau(H) approximately tau(P) where tau(H)(tau(P)) is the duration for which
      the cavity is hydrophobic (hydrophilic). Thus, in order to enhance the native
      state yield, the cycling rate, for a given loading rate of the GroEL nanomachine,
      should be maximized. In DAC2, the volume of the cavity is doubled (as happens
      when ATP and GroES bind to GroEL) and the SP-pore interaction simultaneously
      changes from hydrophobic to hydrophilic. In this case, we find greater increase
      in yield of the native state compared to DAC1 at all values of tau.

PMID- 16427653
TI  - Hair canopy of cricket sensory system tuned to predator signals.
AB  - Filiform hairs located on the cerci of crickets are among the most sensitive
      sensors in the animal world and enable crickets to sense the faintest air
      movements generated by approaching predators. While the neurophysiological and
      biomechanical aspects of this sensory system have been studied independently for
      several decades, their integration into a coherent framework was wanting. In
      order to evaluate the hair canopy tuning to predator signals, we built a model of
      cercal population coding of oscillating air flows by the hundreds of hairs on the
      cerci of the sand cricket Gryllus bimaculatus (Insecta: Orthoptera). A complete
      survey of all hairs covering the cerci was done on intact cerci using scanning
      electronic microscopy. An additive population coding of sinusoid signals of
      varying frequencies and velocities taking into account hair directionality
      delivered the cercal canopy tuning curve. We show that the range of frequencies
      and velocities at which the cricket sensory system is best tuned corresponds to
      the values of signals produced by approaching predators. The relative frequencies
      of short (< 0.5 x 10(-3) m) and long hairs and their differing responses to
      oscillating air flows therefore enable crickets to detect predators in a time
      frequency-intensity space both as far as possible and at close range.

PMID- 16427654
TI  - Localized contacts between hosts reduce pathogen diversity.
AB  - We investigate the dynamics of a simple epidemiological model for the invasion by
      a pathogen strain of a population where another strain circulates. We assume that
      reinfection by the same strain is possible but occurs at a reduced rate due to
      acquired immunity. The rate of reinfection by a distinct strain is also reduced
      due to cross-immunity. Individual based simulations of this model on a 'small
      world' network show that the proportion of local contacts in the host contact
      network structure significantly affects the outcome of such an invasion, and as a
      consequence will affect the patterns of pathogen evolution. In particular, hosts
      interacting through a 'small-world' network of contacts support lower prevalence
      of infection than well-mixed populations, and the region in parameter space for
      which an invading strain can become endemic and coexist with the circulating
      strain is smaller, reducing the potential to accommodate pathogen diversity. We
      discuss the underlying mechanisms for the reported effects, and we propose an
      effective mean-field model to account for the contact structure of the host
      population in 'small-world' networks.

PMID- 16427655
TI  - Asymptotic distribution of stage-grouped population models.
AB  - Matrix models are often used to predict the dynamics of size-structured or age
      structured populations. The asymptotic behaviour of such models is defined by
      their malthusian growth rate lambda, and by their stationary distribution w that
      gives the asymptotic proportion of individuals in each stage. As the coefficients
      of the transition matrix are estimated from a sample of observations, lambda and
      w can be considered as random variables whose law depends on the distribution of
      the observations. The goal of this study is to specify the asymptotic law of
      lambda and w when using the maximum likelihood estimators of the coefficients of
      the transition matrix. We prove that lambda and w are asymptotically normal, and
      the expressions of the asymptotic variance of lambda and of the asymptotic
      covariance matrix of w are given. The convergence speed of lambda and w towards
      their asymptotic law is studied using simulations. The results are applied to a
      real case study that consists of a Usher model for a tropical rain forest in
      French Guiana. They permit to assess the number of trees to measure to get a
      given precision on the estimated asymptotic diameter distribution, which is an
      important information on tropical forest management.

PMID- 16427656
TI  - Environmentally induced dispersal under heterogeneous logistic growth.
AB  - We consider a single-species model which is composed of several habitats
      connected by linear migration rates and having logistic growth. A spatially
      varying, temporally constant environment is introduced by the non-homogeneity of
      its carrying capacity. Under this condition any type of purely diffusive
      behavior, characterized in our model by symmetric migration rates, produces an
      unbalanced population distribution, i.e. some locations receive more individuals
      than can be supported by the environmental carrying capacity, while others
      receive less. Using an evolutionarily stable strategy (ESS) approach we show that
      an asymmetric migration mechanism, induced by the heterogeneous carrying capacity
      of the environment, will be selected. This strategy balances the inflow and
      outflow of individuals in each habitat (balanced dispersal), as well as
      'balancing' the spatial distribution relative to variation in carrying capacity
      (the Ideal Free Distribution from habitat selection theory). We show that several
      quantities are maximized or minimized by the evolutionarily stable dispersal
      strategy.

PMID- 16427657
TI  - Epithelial tissue architecture protects against cancer.
AB  - We consider the design of colon crypts from the point of view of minimizing the
      likelihood of generation of cancerous mutations. A stochastic mathematical model
      (a finite branching process) is developed and fully analyzed. It is found that
      depending on the mutation rates, different designs are evolutionarily
      advantageous. If the mutation rates associated with stem cells are a lot higher
      than the mutation rates of daughter cells, then few stem cells per crypt is the
      evolutionarily optimal strategy. If the mutation rates of stem cells are of the
      same order of magnitude or lower than those for daughter cells, then having as
      many stem cells per crypt as possible is the desirable design. We also found that
      the optimal evolutionary strategy may work very well to protect the organism from
      cancer in the young age, but the same strategy becomes detrimental as the
      organism ages. It pushes the onset of cancer back in time, but it results in an
      elevated cancer initiation rates as the organism gets older. Our model quantifies
      the idea that cancer and aging are the two sides of one coin.

PMID- 16427658
TI  - On the transmission of HIV with self-protective behavior and preferred mixing.
AB  - An epidemic model of HIV transmission with self-protective behavior and preferred
      mixing is presented. Individuals in the model are assumed to choose their levels
      of risk behavior by comparing the costs and benefits of self-protective actions.
      Unlike in models which treat individual risk behavior as exogenously given and
      fixed, the condition under which an endemic steady state equilibrium exists does
      not depend on the extent of assortative mixing in the population. Specifically, a
      unique endemic equilibrium exists when the basic reproductive number of the
      disease, which is given in the model by the expected number of secondary
      infections caused by an infected individual in the absence of any self
      protection, is strictly greater than one. Otherwise, the disease-free equilibrium
      is the only steady state equilibrium. With respect to changes in contact
      patterns, it is shown that, if the degree of preferred mixing is increased, the
      disease prevalence can decrease in the high-risk subpopulation consisting of
      individuals who are more likely to engage in unsafe practices. The situation is
      reversed for the low-risk subpopulation, which is composed of individuals who are
      less willing to engage in risky practices, so that increasing the likelihood of
      mixing with members of one's own group may increase the prevalence level within
      the low-risk subpopulation.

PMID- 16427659
TI  - An application of a two-level non-Gaussian state-space model in the analysis of
      longitudinal papilloma count data.
AB  - In this study, a dynamic Bayesian two-level non-Gaussian state-space model is
      applied in the statistical analysis of longitudinal detectable papilloma count
      data. This two-level model is established on the basis of the state and hyper
      state parameters that depend on the model parameters of biological significance,
      namely, the initiation rate of normal cells and the birth- and death-rates of
      initiated cells. As the time-dependent model parameters fluctuate dynamically and
      stochastically over time, so will the state and hyper-state parameters; thus,
      smoothness priors that allow a wide range of shapes with no specific forms
      required on the state/hyper-state parameters can be employed in this model. Gibbs
      sampler, a Markov chain Monte Carlo approach, is used to implement the Bayesian
      inferences on the state as well as the hyper-state parameters; and the estimates
      of the model parameters can be obtained thereon. Illustrations of the Bayesian
      inference procedure are given by using the datasets from a simulation study as
      well as a laboratory experiment by Brook et al. [E.A. Brooks, C.M. Kohn, P.J.M.
      van Birgelen, G.W. Lucier, C.J. Portier, Stochastic models for papilloma
      formation following exposure to TCDD, Organohalogen Compd. 41 (1999) 521].
      Comparing to the parametric approach that assigns specific forms on the time
      dependent model parameters, different conclusions are drawn by the two-level
      state-space modeling approach considered in this study.

PMID- 16427660
TI  - Novel mechanism for the radiation-induced bystander effect: nitric oxide and
      ethylene determine the response in sponge cells.
AB  - Until now the bystander effect had only been described in vertebrates. In the
      present study the existence of this effect has been demonstrated for the
      phylogenetically oldest metazoan phylum, the Porifera. We used the demosponge
      Suberites domuncula for the experiments in the two-chamber-system. The lower dish
      contained irradiated "donor" cells (single cells) and the upper dish the
      primmorphs ("recipient" primmorphs). The "donor" cells were treated with UV-B
      light (40 mJ/cm2) and 100 microM hydrogen peroxide (H2O2), factors that exist
      also in the natural marine aquatic environment of sponges; these factors caused a
      high level of DNA strand breaks followed by a reduced viability of the cells. If
      these cells were added to the "recipient" primmorphs these 3D-cell cultures
      started to undergo apoptosis. This effect could be abolished by the NO-specific
      scavenger PTIO and ethylene. The conclusion that NO is synthesized by the UV
      B/H2O2-treated cells was supported analytically. The cDNA encoding the enzyme
      dimethylarginine dimethylaminohydrolase (DDAH) was isolated from the "donor"
      cells. High levels of DDAH transcripts were measured in UV-B/H2O2-treated "donor"
      cells while after ethylene treatment the steady-state level of expression drops
      drastically. We conclude that in the absence of ethylene the concentration of the
      physiological inhibitor for the NO synthase ADMA is low, due to the high level of
      DDAH. In consequence, high amounts of NO are released from "donor" cells which
      cause apoptosis in "recipient" primmorphs. In contrast, ethylene reduces the DDAH
      expression with the consequence of higher levels of ADMA which prevent the
      formation of larger amounts of NO. This study describes the radiation-induced
      bystander effect also for the most basal metazoans and demonstrates that this
      effect is controlled by the two gases NO and ethylene.

PMID- 16427661
TI  - Effect of the attention deficit/hyperactivity disorder drug atomoxetine on
      extracellular concentrations of norepinephrine and dopamine in several brain
      regions of the rat.
AB  - Atomoxetine is a selective inhibitor of norepinephrine transporters and is
      currently being used in the pharmacotherapy of attention deficit/hyperactivity
      disorder (ADHD). We have previously shown that atomoxetine increased
      extracellular (EX) concentrations of norepinephrine and dopamine in prefrontal
      cortex, but unlike the psychostimulant methylphenidate, did not alter
      dopamine(EX) in nucleus accumbens or striatum. Using the in vivo microdialysis
      technique in rat, we investigated the effects of atomoxetine on
      norepinephrine(EX) and dopamine(EX) concentrations in several other brain regions
      and also evaluated the role of inhibitory autoreceptors on atomoxetine-induced
      increases of norepinephrine(EX) concentrations. Atomoxetine (3mg/kg i.p.)
      increased norepinephrine(EX) robustly in prefrontal cortex, occipital cortex,
      lateral hypothalamus, dorsal hippocampus and cerebellum, suggesting that
      norepinephrine(EX) is increased throughout the brain by atomoxetine. In lateral
      hypothalamus and occipital cortex where dopamine(EX) was quantifiable,
      atomoxetine did not increase dopamine(EX) concentrations, in contrast to parallel
      increases of norepinephrine(EX) and dopamine(EX) in prefrontal cortex, indicating
      a unique effect in prefrontal cortex. Administration of the alpha(2)-adrenergic
      antagonist idazoxan 1h after atomoxetine resulted in increases in prefrontal
      cortical norepinephrine efflux greater than either compound alone, indicating an
      attenuating effect of the adrenergic autoreceptors on norepinephrine efflux.

PMID- 16427662
TI  - P2X(7) receptors exert a permissive role on the activation of release-enhancing
      presynaptic alpha7 nicotinic receptors co-existing on rat neocortex glutamatergic
      terminals.
AB  - Adenosine triphosphate (ATP) has been reported to enhance the release of
      glutamate by acting at P2X presynaptic receptors. Acetylcholine (ACh) can elicit
      glutamate release through presynaptic nicotinic cholinergic receptors (nAChRs) of
      the alpha7 subtype situated on glutamatergic axon terminals, provided that the
      terminal membrane is weakly depolarized. Considering that ATP and ACh are co
      transmitters, we here investigate on the possibility that P2X and nAChRs co-exist
      and interact on the same glutamatergic nerve endings using purified rat neocortex
      synaptosomes in superfusion. ATP evoked Ca(2+)-dependent release of pre
      accumulated D-[(3)H]aspartate ([(3)H]D-ASP) as well as of endogenous glutamate; (
      )-nicotine, inactive on its own, potentiated the ATP-evoked release. The ATP
      analogue benzoylbenzoylATP (BzATP) behaved like ATP, but was approximately 30
      times more potent; the potentiation of the BzATP-evoked release was blocked by
      methyllycaconitine or alpha-bungarotoxin. Adding inactive concentrations of (-)
      nicotine, epibatidine or choline together with inactive concentrations of BzATP
      resulted in significant elevation of the [(3)H]D-ASP release mediated by alpha7
      nAChRs. To conclude, P2X(7) receptors and alpha7 nAChRs seem to co-exist and
      interact on rat neocortex glutamatergic terminals; in particular, P2X(7)
      receptors exert a permissive role on the activation of alpha7 nAChRs, suggesting
      that ATP may not only evoke glutamate release on its own, but may also regulate
      the release of the amino acid elicited by ACh.

PMID- 16427663
TI  - Effects of ketamine on acute somatic nociception in wild-type and N-methyl-D
      aspartate (NMDA) receptor epsilon1 subunit knockout mice.
AB  - Although the properties of ketamine appear to be well characterized, there is a
      lot of ambiguity in the literature regarding its analgesic effects. After careful
      selection of proper experimental conditions and drug doses, we systematically
      characterized the effects of systemic ketamine on acute somatic nociception in
      mice and examined the role of the NMDA receptor epsilon1 subunit in mediating its
      analgesia. Intraperitoneal administration of ketamine was not analgesic in any of
      the phasic pain assays (thermal, mechanical, electrical) applied to C57BL/6 (wild
      type) and NMDA receptor epsilon1 subunit knockout (mutant) mice. Surprisingly,
      rather than being analgesic for thermal nociception, ketamine showed
      pronociceptive properties in case of low-intensity heat stimulation in wild-type
      mice. In the formalin test (tonic pain), ketamine significantly reduced phase 2
      nociceptive behavior in both wild-type and mutant mice. These data indicate that
      in wild-type mice ketamine has no analgesic effect on phasic pain in normal
      somatic tissues, but alleviates tonic pain after inflammation. Such analgesic
      spectrum of ketamine can be fully explained by its NMDA receptor antagonist
      properties. The results for the mutant mice suggest that the epsilon1 subunit of
      the NMDA receptor does not mediate the analgesic effects of ketamine in tonic
      pain.

PMID- 16427664
TI  - Different roles of two nitric oxide activated pathways in spinal long-term
      potentiation of C-fiber-evoked field potentials.
AB  - There is accumulating evidence implicating the involvement of nitric oxide (NO)
      in spinal central sensitization. The long-term potentiation (LTP) of spinal C
      fiber-evoked field potentials is considered as a fundamental mechanism of
      sensitization of nociceptive neurons in the spinal cord. The present study
      examined the roles of soluble guanylate cyclase (sGC) or ADP-ribosyltransferase
      (ADPRT), two potential NO targets, in spinal LTP. The results showed that (1)
      administration of sGC inhibitors, methyl blue (MB, 4mM, 20 microl) or 1H
      [1,2,4]oxadiazolo[4,3-a]-quiloxalin-1-one (ODQ, 10 microM, 20 microl) before
      tetanic stimulation, significantly inhibited the induction of spinal LTP, and
      this was reversed by 8-Br-cGMP, a membrane-permeable cGMP analog. However, the
      maintenance of spinal LTP was not changed when application of ODQ 2h after
      tetanic stimulation. (2) Although our previous experiments have identified a key
      role for NO in the induction of spinal LTP, NO synthase (NOS) inhibitor, L-NAME
      (1mM, 20 microl) or hemoglobin (2mg/ml, 20 microl), a scavenger of NO, had no
      effect on established spinal LTP when applied 2h after the induction of spinal
      LTP. (3) The mono-ADPRT inhibitor, nicotinamide (10mM, 20 microl), had no effect
      on the induction and maintenance of spinal LTP. However, the poly-ADPRT
      inhibitor, benzamide (100 microM, 20 microl), inhibited its maintenance, but not
      its induction. The results suggest that NO-stimulated guanylyl cyclase activity
      plays a critical role in the induction of LTP of C-fiber-evoked field potentials
      in the spinal cord, whereas NO-related poly-ADPRT activity contributes to the
      maintenance of spinal LTP.

PMID- 16427665
TI  - meso-Dihydroguaiaretic acid attenuates the neurotoxic effect of staurosporine in
      primary rat cortical cultures.
AB  - The effect of meso-dihydroguaiaretic acid (MDGA) on the staurosporine-induced
      neuronal apoptosis and its potential mechanism were investigated using primary
      cultures of rat cortical cells as an assay system. Treatment of MDGA at the
      concentrations of 0.1, 1.0 and 10 microM significantly protected neuronal cells
      against Staurosporine-induced apoptosis. The neuroprotective activity of MDGA was
      the most potent at the concentration of 1.0 microM and was not increased at
      higher concentration. MDGA reduced apoptotic characteristics induced by STS; MDGA
      reduced the condensed nuclei in staurosporine-injured rat cortical cells. MDGA
      diminished the calcium influx that accompanies the staurosporine-induced
      apoptosis, and inhibited the subsequent overproduction of reactive oxygen species
      and peroxide to the level of control cells. It also preserved cellular activity
      of superoxide dismutase, an antioxidative enzyme reduced by staurosporine insult.
      In addition, MDGA significantly inhibited caspase-3/7 activation and cytochrome c
      release. Taken together, these results suggested that MDGA protected neuronal
      cells against staurosporine-induced apoptosis through the inhibition of Ca(2+)
      influx, cellular oxidation, cytochrome c release and caspase-3/7 activation.

PMID- 16427667
TI  - Overexpression of the Saussurea medusa chalcone isomerase gene in S. involucrata
      hairy root cultures enhances their biosynthesis of apigenin.
AB  - Saussurea involucrata is a medicinal plant well known for its flavonoids,
      including apigenin, which has been shown to significantly inhibit tumorigenesis.
      Since naturally occurring apigenin is in very low abundance, we took a transgenic
      approach to increase apigenin production by engineering the flavonoid pathway. A
      construct was made to contain the complete cDNA sequence of the Saussurea medusa
      chalcone isomerase (CHI) gene under the control of the cauliflower mosaic virus
      (CaMV) 35S promoter. Using an Agrobacterium rhizogenes-mediated transformation
      system, the chi overexpression cassette was incorporated into the genome of S.
      involucrata, and transgenic hairy root lines were established. CHI converts
      naringenin chalcone into naringenin that is the precursor of apigenin. We
      observed that transgenic hairy root lines grew faster and produced higher levels
      of apigenin and total flavonoids than wild-type hairy roots did. Over a culture
      period of 5 weeks, the best-performing line (C46) accumulated 32.1 mgL(-1)
      apigenin and 647.8 mgL(-1) total flavonoids, or 12 and 4 times, respectively,
      higher than wild-type hairy roots did. The enhanced productivity corresponded to
      elevated CHI activity, confirming the key role that CHI played for total
      flavonoids and apigenin synthesis and the efficiency of the current metabolic
      engineering strategy.

PMID- 16427666
TI  - Extension of corticocortical afferents into the anterior bank of the
      intraparietal sulcus by tool-use training in adult monkeys.
AB  - When humans use a tool, it becomes an extension of the hand physically and
      perceptually. Common introspection might occur in monkeys trained in tool-use,
      which should depend on brain operations that constantly update and automatically
      integrate information about the current intrinsic (somatosensory) and the
      extrinsic (visual) status of the body parts and the tools. The parietal cortex
      plays an important role in using tools. Intraparietal neurones of naive monkeys
      mostly respond unimodally to somatosensory stimuli; however, after training these
      neurones become bimodally active and respond to visual stimuli. The response
      properties of these neurones change to code the body images modified by
      assimilation of the tool to the hand holding it. In this study, we compared the
      projection patterns between visually related areas and the intraparietal cortex
      in trained and naive monkeys using tracer techniques. Light microscopy analyses
      revealed the emergence of novel projections from the higher visual centres in the
      vicinity of the temporo-parietal junction and the ventrolateral prefrontal areas
      to the intraparietal area in monkeys trained in tool-use, but not in naive
      monkeys. Functionally active synapses of intracortical afferents arising from
      higher visual centres to the intraparietal cortex of the trained monkeys were
      confirmed by electron microscopy. These results provide the first concrete
      evidence for the induction of novel neural connections in the adult monkey
      cerebral cortex, which accompanies a process of demanding behaviour in these
      animals.

PMID- 16427668
TI  - In vitro shoot and root organogenesis, plant regeneration and production of
      tropane alkaloids in some species of Schizanthus.
AB  - A rapid in vitro propagation system leading to formation of shoots from callus,
      roots, and plantlets was developed for Schizanthus hookeri Gill. (Solanaceae), an
      endemic Chilean plant. The genus Schizanthus is of particular interest due to the
      presence of several tropane alkaloids. So far, in vitro propagation of species of
      this genus has not been reported. Propagation of S. hookeri consisted of two
      phases, the first one for callus initiation and shoot formation and the second
      for rhizogenesis and plantlet regeneration. From a single callus that rapidly
      increased in cell biomass (from approximately 50 mg to approximately 460
      mg/culture tube [25 x 130 mm] in 60 days) in the presence of 2.69 microM NAA and
      2.22 microM BA, more than 10 shoots/callus explant were formed. From the latter,
      approx. twenty plantlets formed after 90-110 days shoot subculture in medium
      devoid of growth regulators that favored root formation. Ten alkaloids ranging
      from simple pyrrolidine derivatives to tropane esters derived from angelic,
      tiglic, senecioic or methylmesaconic acids were obtained from in vitro
      regenerated plantlets. One of them, 3alpha-methylmesaconyloxytropane, was not
      previously described. The same growth conditions, as well as other growth
      regulator levels tested, were required to induce callus and root formation in S.
      grahamii Gill. Root organogenesis occurred despite a high level of BA vs. NAA
      used, (i.e., 4.44 microM BA and 0.54 microM NAA); however no shoot formation was
      achieved. In the case of S. tricolor Grau et Gronbach, only callus formation was
      obtained in the presence of various growth regulators.

PMID- 16427669
TI  - Evolutionary game dynamics with non-uniform interaction rates.
AB  - The classical setting of evolutionary game theory, the replicator equation,
      assumes uniform interaction rates. The rate at which individuals meet and
      interact is independent of their strategies. Here we extend this framework by
      allowing the interaction rates to depend on the strategies. This extension leads
      to non-linear fitness functions. We show that a strict Nash equilibrium remains
      uninvadable for non-uniform interaction rates, but the conditions for
      evolutionary stability need to be modified. We analyze all games between two
      strategies. If the two strategies coexist or exclude each other, then the
      evolutionary dynamics do not change qualitatively, only the location of the
      equilibrium point changes. If, however, one strategy dominates the other in the
      classical setting, then the introduction of non-uniform interaction rates can
      lead to a pair of interior equilibria. For the Prisoner's Dilemma, non-uniform
      interaction rates allow the coexistence between cooperators and defectors. For
      the snowdrift game, non-uniform interaction rates change the equilibrium
      frequency of cooperators.

PMID- 16427670
TI  - Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed
      rats are modulated by mast cells and differentially by neuropeptides and nitric
      oxide.
AB  - We have used a pharmacological approach to study the mechanisms underlying the
      rat lung injury and the airway reactivity changes induced by inhalation of
      formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The
      reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose
      response curves to methacholine (MCh). Local and systemic inflammatory phenomena
      were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL)
      fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to
      MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found
      after FA inhalation as compared with naive rats. Also, FA exposure significantly
      increased the total cell numbers in BAL, in peripheral blood and in the spleen,
      but did not modify the counts in bone marrow. Capsaicin hindered the increase of
      leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80
      and indomethacin were able to prevent the lung neutrophil influx after FA, but
      indomethacin had no effect on that of mononuclear cells. Following FA inhalation,
      the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO)
      synthase inhibitor L-NAME, significantly reduced the total cell number in BAL.
      Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA
      inhalation, whereas capsaicin was inactive in this regard. On the other hand,
      indomethacin exacerbated BHR. These data suggest that after FA inhalation, the
      resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory
      fibers and mast cell-derived mediators. The effect of NO seemed to be largely
      restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to
      the inflammatory response, therefore indicating that the mechanisms responsible
      for the changes of airway responsiveness caused by FA may be separate from those
      underlying its inflammatory lung effects.

PMID- 16427671
TI  - Can general anaesthesia be used for the Paralytic Shellfish Poison bioassay?
AB  - The current method for Paralytic Shellfish Poisoning (PSP) testing in shellfish
      is based on the mouse bioassay (MBA), which involves injecting shellfish extract
      into a conscious mouse, and then converting its time to death into PSP toxicity
      using Sommer's table. To improve animal welfare, the present study investigated
      the use of anaesthesia. A saxitoxin (STX) calibration study was conducted where
      known amounts of STX were injected into both unanaesthetised and anaesthetised
      mice. Death time was approximately doubled when mice were anaesthetised. Both
      unanaesthetised and anaesthetised animals showed a linear relationship between
      the inverse death time and log(STX). Based on these data, new calibration curves
      were developed. This study revealed that the current method employing Sommer's
      table underestimates toxicity by up to 50% for higher toxin levels. Subsequently,
      shellfish samples were tested on both unanaesthetised and anaesthetised mice.
      Using the new calibration curves, the numbers of samples exceeding the field
      closure limit were similar for unanaesthetised and anaesthetised mice, and were
      nearly two-fold higher than those obtained with the current method. The studies
      showed that the bioassay gives variable results for both unanaesthetised and
      anaesthetised animals. Anaesthesia forms a viable and more ethical alternative to
      the current bioassay, at least in the short term. A practical summary on how to
      conduct this method is given.

PMID- 16427672
TI  - Effects of Crotalus durissus collilineatus venom in the isolated rat kidney.
AB  - Ophidian accidents caused by the subspecies Crotalus durissus are responsible for
      high morbity and mortality rates. Acute renal failure is a common complication
      observed in these accidents. The aim of the present study was to investigate the
      renal effects promoted by the venom of C. d. collilineatus and its fractions,
      crotoxin and phospholipase A2. C. d. collilineatus (Cdc; 30 microg mL(-1)),
      crotoxin (CTX; 10 microg mL(-1)) and phospholipase A2 (PLA2; 10 microg mL(-1))
      were tested in isolated rat kidney. The first 30 min of each experiment were used
      as an internal control and Cdc or its fractions, CTX and PLA2 were added to the
      system after this period. All experiments lasted 120 min. The venom of Cdc
      decreased perfusion pressure (PP; control120 = 110.3 +/- 3.69 mmHg; Cdc120 =
      96.7+/-8.1 mmHg), renal vascular resistance (RVR; control120 = 6.42+/-0.78 mmHg
      mL g(-1) min(-1); Cdc120 = 4.8+/-0.56 mmHg/mL g(-1) min(-1)), urinary flow (UF;
      control120 = 0.19+/-0.03 mL g(-1) min(-1); Cdc120 = 0.12 +/- 0.01 mL g(-1) min(
      1)), and glomerular filtration rate (GFR; control120 = 0.79 +/- 0.07 mL g(-1)
      min(-1); Cdc120 = 0.53 +/- 0.09 mL g(-1) min(-1)), but had no effect on the
      percent of sodium tubular transport (%TNa+), percent of chloride tubular
      transport (%TK+) and percent of potassium tubular transport (%TCl-). CTX and PLA2
      reduced the GFR, while UF, PP and RVR remained stable during the full 120 min of
      perfusion. Crotoxin administration also diminished the %TK+ (control120 = 69.94
      +/- 6.49; CTX120 = 33.28 +/- 4.78) and %TCl- (control120 = 79.53 +/- 2.67; CTX120
      = 64.62 +/- 6.93). PLA2 reduced the %TK+, but exerted no effect on the %TNa+ or
      on that of TCl-. In conclusion, the C. d. collilineatus venom altered the renal
      functional parameters evaluated. We suggest that crotoxin and phospholipase A2
      were involved in this process, since the renal effects observed would be due to
      the synergistic action of the components of the venom.

PMID- 16427674
TI  - Parvovirus B19 genome as a single, two-state replicative and transcriptional
      unit.
AB  - The variation in the amount of parvovirus B19 DNA and different classes of RNA in
      permissive and non-permissive infected cells was analysed by means of
      quantitative real-time PCR and RT-PCR assays. In the permissive bone marrow
      mononuclear cells, UT7/Epo and KU812Ep6 cells, viral DNA usually increased within
      48 hpi, rarely exceeding 2 Logs with respect to input DNA. Viral RNA was always
      present within 2-6 hpi, its increase paralleled that of viral DNA up to 36-48
      hpi, and all the different classes of viral RNA were constantly represented in
      stable relative amounts throughout the infection cycle. In the non-permissive TF
      1 cells, viral DNA did not increase and only one most represented single class of
      viral RNA was detected. Our data do not support the current model for B19 virus
      replication and transcription, consisting in different early and late expression
      patterns, but suggest an alternative model, indicating that the B19 virus genome
      should be considered a single, two-state replicative and transcriptional unit.

PMID- 16427673
TI  - Increased liver pathology in hepatitis C virus transgenic mice expressing the
      hepatitis B virus X protein.
AB  - Transgenic mice expressing the full-length HCV coding sequence were crossed with
      mice that express the HBV X gene-encoded regulatory protein HBx (ATX mice) to
      test the hypothesis that HBx expression accelerates HCV-induced liver
      pathogenesis. At 16 months (mo) of age, hepatocellular carcinoma was identified
      in 21% of HCV/ATX mice, but in none of the single transgenic animals. Analysis of
      8-mo animals revealed that, relative to HCV/WT mice, HCV/ATX mice had more severe
      steatosis, greater liver-to-body weight ratios, and a significant increase in the
      percentage of hepatocytes staining for proliferating cell nuclear antigen.
      Furthermore, primary hepatocytes from HCV, ATX, and HCV/ATX transgenic mice were
      more resistant to fas-mediated apoptosis than hepatocytes from nontransgenic
      littermates. These results indicate that HBx expression contributes to increased
      liver pathogenesis in HCV transgenic mice by a mechanism that involves an
      imbalance in hepatocyte death and regeneration within the context of severe
      steatosis.

PMID- 16427675
TI  - Caspase-3 and -7 mediate apoptosis of human Chang's conjunctival cells induced by
      enterovirus 70.
AB  - Enterovirus 70 (EV70) is the major etiological agent of acute hemorrhagic
      conjunctivitis (AHC). EV70 m.o.i.- (multiplicity of infection) and time
      dependently induced apoptosis in human Chang's conjunctival (HCC) cells. UV- or
      heat-inactivated EV70 did not induce apoptosis. EV70-induced apoptosis was
      inhibited by cycloheximide and methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone
      (MPCMK), but not actinomycin D and guanidine.HCl (although guanidine.HCl
      inhibited the apoptosis induced by EV70 infection at 0.5 PFU/cell for 18 h). EV70
      infection induced activation of caspase-3 and -7 and degradation of the
      constitutively activated caspase-6. EV70-induced apoptotic DNA ladders and
      activated caspase-3 and -7, correlated with virus release. Caspase inhibitor IX
      (Z-VD-FMK) inhibited EV70-induced apoptosis and virus release, but not
      intracellular viral production. The results suggest that infectious virus and the
      syntheses of viral proteins especially EV70 proteases, but not viral genome RNA,
      are required for caspase-3 and -7-mediated EV70-induced apoptosis, and that
      apoptosis through cell lysis promotes EV70 release from HCC cells.

PMID- 16427676
TI  - Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the
      nuclear lamina during herpes simplex virus type 1 egress.
AB  - Cells infected with wild type HSV-1 showed significant lamin A/C and lamin B
      rearrangement, while UL34-null virus-infected cells exhibited few changes in
      lamin localization, indicating that UL34 is necessary for lamin disruption.
      During HSV infection, US3 limited the development of disruptions in the lamina,
      since cells infected with a US3-null virus developed large perforations in the
      lamin layer. US3 regulation of lamin disruption does not correlate with the
      induction of apoptosis. Expression of either UL34 or US3 proteins alone disrupted
      lamin A/C and lamin B localization. Expression of UL34 and US3 together had
      little effect on lamin A/C localization, suggesting a regulatory interaction
      between the two proteins. The data presented in this paper argue for crucial
      roles for both UL34 and US3 in regulating the state of the nuclear lamina during
      viral infection.

PMID- 16427677
TI  - Herpes simplex virus type 1 recombinants without the oriL sequence replicate DNA
      with increased fidelity.
AB  - Herpes simplex virus type 1 (HSV-1) contains three DNA replication origins (ori)
      of two types. The oriL is located in the center of the unique long sequences,
      whereas two copies of oriS, which are structurally different from oriL, are
      within the reiterated sequences flanking the unique short sequences. Recombinant
      viruses were constructed from ts+7, which contains a deletion of oriL sequences,
      to have either the beta-galactosidase gene or the supF amplicon integrated into
      the thymidine kinase locus. Rescue recombinants also were constructed from the
      supF-containing recombinant to restore the deleted oriL to the wild type
      sequences. These recombinants were subjected to mutagenesis assays. Results
      demonstrated that ts+7 viruses with the deletion in oriL sequences replicated
      both target genes with higher fidelity compared to those derived from the
      parental strain KOS. Possible mechanisms leading to the high fidelity of DNA
      replication mediated by viruses without intact oriL sequences are discussed.

PMID- 16427679
TI  - Inhibition of porcine circovirus type 2 replication in mice by RNA interference.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of an emerging
      swine disease, postweaning multisystemic wasting syndrome (PMWS) for which no
      antiviral treatment is available. To exploit the possibility of using RNA
      interference (RNAi) as a therapeutic approach against the disease, plasmid-borne
      short hairpin RNAs (shRNAs) were generated to target the PCV2 genome.
      Transfection of these shRNAs into cultured PK15 cells caused a significant
      reduction in viral RNA production that was accompanied by inhibiting viral DNA
      replication and protein synthesis in infected cells. The effect was further
      tested in vivo in a mouse model that has been developed for PCV2 infection. Mice
      injected with shRNA before PCV2 infection showed substantially decreased
      microscopic lesions in inguinal lymph nodes compared to controls. In situ
      hybridization and immunohistochemical analyses showed that shRNA caused a
      significant inhibition in the level of viral DNA and protein synthesis detected
      in the lymph nodes of the treated mice relative to the controls. Taken together,
      these results indicate that shRNAs are capable of inhibiting PCV2 infection in
      vitro as well as in vivo and thus may constitute an effective therapeutic
      strategy for PCV2 infection.

PMID- 16427678
TI  - Venezuelan equine encephalitis virus entry mechanism requires late endosome
      formation and resists cell membrane cholesterol depletion.
AB  - Virus envelope proteins determine receptor utilization and host range. The choice
      of receptor not only permits specific targeting of cells that express it, but
      also directs the virus into specific endosomal trafficking pathways. Disrupting
      trafficking can result in loss of virus infectivity due to redirection of virions
      to non-productive pathways. Identification of the pathway or pathways used by a
      virus is, thus, important in understanding virus pathogenesis mechanisms and for
      developing new treatment strategies. Most of our understanding of alphavirus
      entry has focused on the Old World alphaviruses, such as Sindbis and Semliki
      Forest virus. In comparison, very little is known about the entry route taken by
      more pathogenic New World alphaviruses. Here, we use a novel contents mixing
      assay to identify the cellular requirements for entry of a New World alphavirus,
      Venezuelan equine encephalitis virus (VEEV). Expression of dominant negative
      forms of key endosomal trafficking genes shows that VEEV must access clathrin
      dependent endocytic vesicles for membrane fusion to occur. Unexpectedly, the exit
      point is different from Old World alphaviruses that leave from early endosomes.
      Instead, VEEV also requires functional late endosomes. Furthermore, unlike the
      Old World viruses, VEEV entry is insensitive to cholesterol sequestration from
      cell membranes and may reflect a need to access an endocytic compartment that
      lacks cholesterol. This indicates fundamental differences in the entry route
      taken by VEEV compared to Old World alphaviruses.

PMID- 16427680
TI  - Stormwater runoff quality and quantity from asphalt, paver, and crushed stone
      driveways in Connecticut.
AB  - This study compared the quality and quantity of stormwater runoff from replicated
      asphalt, permeable paver, and crushed-stone driveways. Rainfall was measured on
      site and runoff was recorded using tipping buckets. Flow-weighted composite
      runoff samples were analyzed weekly for total suspended solids, total Kjeldahl
      nitrogen, nitrate-nitrogen, ammonia-nitrogen, total phosphorus (TP), zinc, lead,
      and copper. Infiltration rate was determined on each driveway annually. Repeated
      measures analysis of variance indicated that stormwater runoff was significantly
      different among each driveway type; the order of decreasing runoff was asphalt>
      paver> stone. Average infiltration rates were 0, 11.2 and 9.0 cm/h for asphalt,
      paver, and crushed stone driveways, respectively. Both paver and crushed stone
      driveways reduced stormwater runoff as compared to asphalt driveways. Runoff from
      paver driveways contained significantly lower concentrations of all pollutants
      measured than runoff from asphalt driveways. However, runoff from crushed stone
      driveways was similar in concentrations to runoff from asphalt driveways, except
      for TP concentrations, which were lower in runoff from crushed stone driveways
      than runoff from asphalt driveways. The mass export of measured pollutants
      followed the relative differences in stormwater runoff, rather than differences
      in concentrations.

PMID- 16427681
TI  - Effects of aluminum treatment on phosphorus, carbon, and nitrogen distribution in
      lake sediment: a 31P NMR study.
AB  - The effects of aluminum (Al) treatment on sediment composition of carbon (C),
      nitrogen (N) and phosphorus (P) were investigated in sediment representing pre-
      and post-treatment years in the Danish Lake Sonderby. 31P NMR spectroscopy
      analysis of EDTA-NaOH extracts revealed six functional P groups. Direct effects
      of the Al treatment were reflected in the orthophosphate profile revealing
      increased amounts of Al-P in the sediment layers representing the post-treatment
      period, as well as changes in organic P groups due to precipitation of
      phytoplankton and bacteria at the time of Al addition. Furthermore, changes in
      phytoplankton community structure and lowered production due to the Al treatment
      resulted in decreased concentrations of sediment organic P groups and total C.
      Exponential regressions were used to describe the diagenesis of C, N, and P in
      the sediment. From these regressions, half-life degradation times and C, N, and P
      burial rates were determined.

PMID- 16427682
TI  - Organotin contamination in the Atlantic Ocean off the Iberian Peninsula in
      relation to shipping.
AB  - Imposex in female snails, a bioindicator of TBT contamination, and the presence
      of organotins in snails' tissue and sediments were studied at nine sites off the
      western Iberian Peninsula. The study was part of a European project (acronym HIC
      TBT) co-financed by the EU-LIFE programme, intending to investigate and
      communicate the impact of organotins from ships in marine ecosystems. Snails and
      sediments were sampled during two cruises in May/June 1999 and in January 2000 in
      areas of high, intermediate and low-shipping density. Imposex was found in female
      snails from several sampling sites, some of which had an imposex incidence of
      100%. Differences in sensitivity were found between species; hence comparison of
      imposex levels between locations where different species were collected was not
      straightforward. Total organotin concentrations in sediments (sum of butyl and
      phenyltin compounds) ranged from 21 to 185 ng Sn g(-1) with higher values for
      most sites sampled in the vicinity of shipping lanes. Organotin concentration in
      snails' tissue ranged from <5 to 196 ng Sn g(-1), which are similar to those
      found in snails from other offshore areas contaminated by TBT. Overall, these
      results give further support to the recent ban on the use of organotin based
      antifouling paints to all ship size.

PMID- 16427683
TI  - Impact of zinc and nickel on oxygen consumption of benthic microbial communities
      assessed with microsensors.
AB  - In this study, the effect of zinc and nickel on oxygen consumption in sediments
      was determined using oxygen microsensors. Sediments from the southwest lagoon of
      New Caledonia, in the vicinity of the city of Noumea, were incubated nearby in
      situ conditions and exposed to Zn and Ni concentrations of 20 and 60 mg l(-1).
      The depth distribution of oxygen consumption was estimated from the steady-state
      oxygen microprofiles, and the effects of metal were compared on the distributions
      before and after spiking. In most cases, metal had a strong effect on oxygen
      consumption at the surface. After 6 h exposure, oxygen consumption was only 10
      40% of the initial value. However, the strong decrease in oxygen consumption
      observed at the sediment surface was counterbalanced by an increase of oxygen
      consumption deeper in the sediment. This is probably due to (i) a downward
      migration of aerobic microbial microorganisms living at the surface in order to
      escape the toxic effect of metal or/and (ii) a switch of the facultative aerobes
      from the low efficiency fermentation mode to the high-energy aerobic respiration
      mode.

PMID- 16427684
TI  - Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human
      papillomavirus-associated pre-malignant and malignant lesions of the uterine
      cervix.
AB  - OBJECTIVES: Humoral and cellular immune responses are likely to play a key role
      for the clearance or persistence and progression of high risk (HR) HPV-associated
      cervical lesions. Although there are many studies describing the systemic T-cell
      responses to HPV16 and 18 proteins, few data are available regarding the cellular
      mucosal immune responses. We used immunohistochemistry to characterize
      populations of T-immune cells (CD4+, CD8+, CD45RO+) in HR-HPV-infected
      precancerous and cancerous lesions of the uterine cervix. METHODS: Four biopsies
      from normal cervix, 9 CIN1 which have regressed (rCIN), 5 CIN1 which have
      progressed (pCIN) to high grade lesions, 13 CIN3 and 11 invasive carcinomas were
      included. All dysplasias and carcinomas were HR-HPV-positive and low-risk-HPV
      negative. They were stained with monoclonal antibodies specific for CD4, CD8 and
      CD45RO and examined by microscopy. STATISTICAL ANALYSIS: The Kruskal-Wallis test
      and the Siegel's and Castelan's method were used. RESULTS.: CD4+ cells
      predominated in regressing CIN1 both within the stroma and the epithelium with
      the highest CD4+/CD8+ ratio compared with pCIN1, CIN3 and invasive carcinoma. At
      the exception of CD45RO+ cells, T cells were detected with similar frequencies in
      both pCIN1 and CIN3. However, in 7 out of 10 CIN3, CD4+ and CD8+ cells were
      visible as organized lymphoid follicle structure. The CD8+ and CD45RO+ cells far
      exceeded the CD4+ cells in invasive cancers. CONCLUSIONS: Density and
      distribution of immune T cells depend on the malignant potential of HR-HPV
      lesions. These results suggest that the studied lymphocyte subsets have an
      important role to fulfil during the natural history of HR-HPV-associated lesions.

PMID- 16427685
TI  - Effective palliative radiotherapy for symptomatic recurrent or residual ovarian
      cancer.
AB  - OBJECTIVE: To evaluate the efficacy of radiotherapy (RT) for symptomatic
      recurrent or residual ovarian cancer. METHODS: A review was conducted on patients
      (pts) treated with palliative RT for symptomatic ovarian cancer at The Ottawa
      Hospital Regional Cancer Centre between 1990 and 2003. Patient demographics,
      tumor factors, treatment variables, and clinical outcome were entered into a
      database. Symptom response was defined as complete (CR), partial (PR), or none.
      RESULTS: 62 courses of RT were delivered to 53 pts. The symptoms treated were:
      bleeding (40%), pain (37%), and "others" (23%). The most common dose
      fractionation scheme was 30 Gy in 10 fractions (f) (range: 5 Gy/1 f to 52.5 Gy/20
      f). The overall response rate was 100%, with 68% achieving a CR. The CR rates
      were 88, 65, and 36% for the symptoms of bleeding, pain, and "others",
      respectively (P = 0.003). The median duration of response was 4.8 months (range:
      1-71 months). In multivariate analysis, the only factors that were found to be
      significant positive predictors of symptom control were: the symptom bleeding (P
      = 0.015) and stage III/IV disease at presentation (P = 0.01). The most commonly
      reported toxicities were grades 1 and 2 nausea/vomiting and diarrhea. There were
      no grade 3/4 toxicities reported. CONCLUSIONS: Radiotherapy is highly effective
      in palliating symptomatic ovarian cancer. Excellent results are achieved for
      patients presenting with bleeding or pain. Symptomatic patients should be
      strongly considered for palliative radiotherapy. Higher doses of radiotherapy
      should be considered for those with symptoms other than bleeding or pain and
      those with longer life expectancies.

PMID- 16427686
TI  - Distribution of HPV16 and 18 intratypic variants in normal cytology,
      intraepithelial lesions, and cervical cancer in a Mexican population.
AB  - OBJECTIVE: Several intratype variants of HPV16 and 18 have been identified. These
      variants are associated with populations from different geographic regions, and
      show a differential distribution among the severity of the cervical lesion, most
      likely due to different pathogenic potential. The objective of this study was to
      investigate the variant distribution of HPV16 and 18 in a Mexican population and
      its association with the severity of the cervical lesion and the histological
      lineage of cervical cancer. METHODS: HPV types 16 and 18 detection was performed
      in 412 samples of preinvasive and invasive specimens from patients attending a
      Primary Health-Care Center, an Early Cervical Lesion Clinic, or a Cancer Center.
      Distribution of HPV variants was correlated with the cytological findings and
      tumor cell types using contingency tables. Statistical difference was tested with
      the Fisher's Exact Test or its Fisher-Freeman-Halton extension for RXC tables.
      Alpha value was set at the P < 0.05. RESULTS: Among the 277 women included in
      this study without cancer, 63.5% (176 cases) had a normal cytology; from the
      remaining 101 women, 53.5% were LSIL (54 cases), and 46.5% HSIL (47 cases). From
      a total of 135 invasive carcinomas, 78.5% were squamous (106 cases); 6.6%
      adenocarcinoma (9 cases); 9.6% adenosquamous (ADSC) (13 cases); and 5.1% were
      undifferentiated carcinoma (7 cases). HPV16 E and AA-a were evenly distributed
      among preinvasive and invasive lesions. However, the isolate AA-c was exclusively
      found in cervical cancer. HPV18 Var-1(E) was almost exclusively found in invasive
      lesions, while the HPV18 Var-2(Af) predominated in normal or preinvasive lesions.
      In invasive cancer, this variant was found only in squamous tumors. CONCLUSIONS:
      The differential distribution of HPV16 and 18 variants in cervical lesions we
      found further supports experimental data on the different pathogenic potential of
      HPV16 and 18 variants for cervical cancer development.

PMID- 16427687
TI  - Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase
      in uterine cervical cancer.
AB  - OBJECTIVE: To determine the association of human papillomavirus (HPV) infection
      with the expression of dihydrodiol dehydrogenase (DDH) in uterine cervical cancer
      (UCC). METHODS: In situ hybridization (ISH) and immunohistochemistry were applied
      to examine pathological specimens of 145 patients with UCC. RESULTS: By ISH,
      HPV16/18 DNA was detected in 108 (74.5%) UCC cases. DDH expression determined by
      immunohistochemistry was detected in 81 (75%) lesions among 108 HPV-positive
      cases. In contrast, of 37 HPV-negative cases, DDH was only detected in 16 (43.2%)
      of the lesions. A significant correlation was found between DDH expression and
      the presence of HPV (P < 0.001), FIGO stage (P = 0.004), lymph node involvement
      (P < 0.001), as well as patients' survival (P = 0.002). In vitro, DDH expression
      was also found closely associated with HPV infection, and DDH content was
      proportional to cell sensitivity for cisplatin and doxorubicin. CONCLUSIONS: HPV
      infection provokes local inflammation, which can then induce DDH expression and
      drug resistance in UCC. The detailed biological relationship among HPV infection,
      expression of DDH and drug resistance, however, remains to be clarified.

PMID- 16427688
TI  - Cervical cancer: value of an endovaginal coil magnetic resonance imaging
      technique in detecting small volume disease and assessing parametrial extension.
AB  - BACKGROUND: Estimation of tumor volume by endovaginal magnetic resonance (MR)
      imaging is a better indicator of prognosis than FIGO stage in women with cervical
      cancer treated by standard modalities. However, the introduction of fertility
      conserving surgical techniques makes fresh demands upon imaging of these small
      tumors. OBJECTIVE: To determine the sensitivity and specificity of endovaginal
      MRI in detecting small volume disease and assessing parametrial extension in
      uterine cervical cancer by comparing the findings with those at radical
      hysterectomy in order to establish its role in guiding the surgical decision
      making process preoperatively. METHODS: A retrospective study was performed in
      119 patients who underwent endovaginal and external phased array MR imaging at
      0.5 T or 1.5 T before radical hysterectomy. Tumor presence within the cervix and
      parametrial extension was noted on the endovaginal images. Histopathological
      findings were correlated with MR imaging results for all patients. RESULTS: The
      sensitivity and specificity for detecting tumor by endovaginal MR imaging in the
      119 patients were 96.9 and 59.0%, respectively. Thirty-six percent of tumors were
      <or=1 cm(3) in volume. For these, sensitivity and specificity for tumor detection
      were 87% and 65% respectively. For evaluation of parametrial status, sensitivity
      was 80%, and specificity was 91.3%. A cut-off MRI tumor volume of 5.2 cm(3)
      predicted histologically confirmed lymph node metastases with a sensitivity of
      78.6% and specificity of 72.5%. CONCLUSION: Endovaginal magnetic resonance
      imaging has high sensitivity in the preoperative staging of uterine cervical
      cancer even for tumors <or=1 cm(3). It is an invaluable technique in planning
      fertility-conserving or radical surgical treatment of early stage cervical
      cancer.

PMID- 16427689
TI  - Identification of prognostic factors after positive second-look surgery in
      epithelial ovarian carcinoma.
AB  - OBJECTIVE: The objective of this study was to identify independent prognostic
      factors for survival in patients with epithelial ovarian cancer who had
      persistent disease identified at second-look surgery. METHODS: We performed a
      retrospective chart review of all patients with epithelial ovarian cancer who had
      positive findings at second-look surgery between June 1991 and June 2002. All
      patients achieved a complete clinical remission after a prescribed course of
      primary therapy. Survival was determined from the time of second-look surgery
      until last follow-up or death. RESULTS: The study included a total of 262
      patients, with a median age of 54 years (range, 22-80). Of the 262 patients, 166
      (63%) had died of disease. Records of initial (salvage) treatment after the
      positive second-look surgery were available for 243 patients. Therapies included
      the following: intraperitoneal (IP) cisplatin, 71 (29%); IP cisplatin combined
      with a second drug, 53 (22%); IP therapy other than cisplatin, 29 (12%);
      intravenous (IV) chemotherapy, 50 (21%); IP and IV therapy, 35 (14%); and oral
      chemotherapy, 5 (2%). Of the 13 potential prognostic factors analyzed, only 2
      factors emerged that, when combined, were significant--residual disease after
      primary surgery and size of persistent disease found at second-look surgery.
      Patients with <or=1 cm residual disease after primary surgery and microscopic
      disease at second-look surgery had significantly improved survival. CONCLUSION:
      In our analysis, the only prognostic factor for survival in patients with
      positive second-look procedures was a combination of residual disease after
      primary surgery and size of persistent disease identified at second-look surgery.
      No individual chemotherapy treatment imparted a survival advantage. Novel that
      therapeutic approaches are needed in this setting.

PMID- 16427690
TI  - Biogenic amine changes in brain regions and attenuating action of Ocimum
      sanctumin noise exposure.
AB  - Broadband white noise exposure (100 dB) in wistar strain male albino rats
      significantly increased the levels of dopamine (DA), serotonin (5-HT) and 5-HT
      turnover in many of the discrete brain regions (cerebral cortex, cerebellum,
      hypothalamus, hippocampus, pons-medulla and corpus striatum) during sub-chronic
      noise exposure (4 h daily for 15 days). In acute (4 h for 1 day) and chronic
      noise exposures (4 h daily for 30 days) the levels were significantly altered
      only in certain regions. The turnover study of serotonin clearly indicates that
      neurotransmitter level alone cannot be an indicator, as in some brain regions the
      rate of synthesis matched with the degradation in order to maintain the normal
      levels. The intraperitoneal administration of 70% ethanolic extract of Ocimum
      sanctum(OS) at the dosage of 100 mg/kg body weight to animals subjected to noise
      exposure has prevented the noise induced increase in neurotransmitter levels
      without affecting the normal levels. This indicates that OS can be a probable
      herbal remedy for noise induced biogenic amine alterations.

PMID- 16427691
TI  - Importance of using guarded techniques for the preparation of endometrial
      cytology smears in mares.
AB  - Material for endometrial cytology can be collected by veterinarians using guarded
      or unguarded swabs, or digitally with a gloved hand, and is an important
      diagnostic tool in establishing the endometrial health of mares prior to
      breeding. The aim of this study was to determine whether the use of unguarded
      endometrial samples is a reliable indicator of the presence of neutrophils in the
      uterus. Duplicate endometrial smears were collected from 41 genitally normal, non
      pregnant fertile mares by both double-guarded swabs (DGS) and in an unguarded
      manner by digital scraping (DS) of the endometrium. In 17 of the 41 mares, smears
      were also collected from the cranial vagina by DS. Cytological samples were
      collected from a further seven non-pregnant mares at different reproductive
      stages, and tissues (vestibule, vagina and cervix) from four reproductively
      normal mares were examined histologically after slaughter to detect the presence
      of neutrophils. Only 3/41 (7.3%) of the DGS endometrial smears had neutrophils
      present compared to 36/41 (87.8%) of the DS endometrial smears. The percentage of
      neutrophils in DGS endometrial smears ranged from 0 to 6% (mean = 0.41%), whereas
      those in the DS smears ranged from 2 to 90% (mean = 22.02%). Neutrophils were
      present in all vaginal smears (17/17, range=3-56% (mean = 22.18%)). There was a
      significant positive correlation (r = 0.84; P < 0.001) between the percentage of
      neutrophils in the vagina and in the DS endometrial smears. More neutrophils were
      found in the cervix, vagina and vestibule than in endometrial smears during the
      cycle (P<0.05). Neutrophils were also observed in tissue collected from the
      cervix, vagina and vestibule from reproductively normal mares at post-mortem. In
      conclusion, endometrial smears collected using unguarded techniques are very
      likely to be contaminated with neutrophils transferred from the vagina
      potentially leading to incorrect diagnosis of endometritis. When collecting
      samples for endometrial cytology it is important to use guarded techniques to
      ensure that only the endometrium is sampled to avoid contamination with cells
      carried over from other areas of the reproductive tract.

PMID- 16427692
TI  - Durability of the resin bond strength to zirconia ceramic after using different
      surface conditioning methods.
AB  - OBJECTIVES: The purpose of this in vitro study was the evaluation of the bond
      strength and its durability of two composite resins to zirconia ceramic after
      using different surface conditioning methods. METHODS: Plexiglas tubes filled
      with composite resin were bonded to zirconia ceramic discs (Cercon) which were
      either in their original state as supplied by the manufacturer only cleaned in
      isopropanol or were cleaned with an air-powder-water spray with sodium
      hydrocarbonate solution or were air abraded (50 microm Al(2)O(3)). Groups of 20
      specimens each were bonded either with a conventional composite resin (Variolink
      II) or with a phosphate monomer (MDP)-containing resin (Panavia F) to the ceramic
      discs. Subgroups of 10 bonded specimens were stored in distilled water (37
      degrees C) for either 3 days or for 150 days. Additionally, the 150 days
      specimens were thermal cycled 37,500 times. Statistical analyses were conducted
      with the Wilcoxon rank sum test adjusted by Bonferroni-Holm. RESULTS: The initial
      tensile bond strength (TBS) for Variolink II ranged from 9.0 to 16.6 MPa and were
      significantly lower (p< or =0.05) than for Panavia F ranging from 18.7 to 45.0
      MPa. Air abrasion resulted in significantly higher TBS (p< or =0.01) than the two
      other surface conditioning methods. After 150 days storage, only the air abraded
      specimens bonded with Panavia F showed high bond strengths of 39.2 MPa, whereas
      most other specimens debonded spontaneously or showed very low bond strengths.
      SIGNIFICANCE: The use of the MDP-containing composite resin Panavia F on air
      abraded zirconia ceramic can be recommended as promising bonding method.

PMID- 16427693
TI  - Adolescents' thoughts about parents' jobs and their importance for adolescents'
      future orientation.
AB  - The current study examined the relation between adolescents' perceptions of their
      parents' jobs and their future orientation, and tested the role of parental
      support. Four hundred and fifteen ninth through twelfth graders were surveyed
      about their parents' job rewards, self-direction, and stressors, as well as their
      expectations for employment and education prospects. Results indicate that
      perceptions of parents' rewards, self-direction, and stress predict how
      positively or negatively adolescents perceive the future to be. Results also
      suggest that higher levels of parental support may weaken the association between
      perceptions and future orientation when adolescents perceive their parents
      experience unfavorable conditions at work. These results suggest that
      adolescents' perceptions of parents' jobs have implications for their preparation
      for adulthood.

PMID- 16427694
TI  - The effect of high-density-lipoprotein on thrombus formation on and endothelial
      cell attachement to biomaterial surfaces.
AB  - Cardiovascular implants such as vascular grafts fail frequently because they lack
      genuine blood-compatibility. The blood-contacting surface should simultaneously
      prevent thrombus formation and promote formation of a confluent endothelial cell
      layer, to achieve sustained haemostasis. Contact activation and
      endothelialization are known to be determined by the plasma proteins which adsorb
      onto virtually all synthetic surfaces almost immediately upon contact with blood.
      A common approach in blood-compatibility research is, therefore, to use
      hydrophilic biomaterials, which are sometimes claimed to be "protein-repellent".
      We report here that, for synthetic polymeric surfaces, hydrophilicity is by no
      means synonymous to protein-repellency. We discovered that significant amounts of
      proteins, especially high-density lipoprotein, adsorb to hydrophilic surfaces.
      Pre-incubation of hydrophilic synthetic surfaces with high-density lipoprotein
      provides a blood-biomaterial interface, which inhibits thrombin generation and
      subsequent thrombus formation, and also accommodates overgrowth with a confluent
      endothelial layer. This approach may open the way to truly functional small
      caliber arterial prostheses, and may also be relevant to cardiovascular tissue
      engineering in which de novo vascular tissues are cultured on or within a
      biomaterial scaffold.

PMID- 16427695
TI  - Infrequent Wnt inhibitory factor-1 (Wif-1) methylation in chronic lymphocytic
      leukemia.
AB  - The Wnt pathway has been shown recently, to be activated in patients with chronic
      lymphocytic leukemia (CLL). This is the first study to examine the role of Wnt
      inhibitory factor-1 (Wif-1) methylation in the pathogenesis of haematolymphoid
      malignancies. Wif-1, a putative tumor suppressor, is a soluble negative regulator
      of the Wnt pathway activated in CLL. We studied the role of methylation of Wif-1
      in 43 Chinese patients with CLL. At diagnosis, Wif-1 methylation was detected in
      5/43 (11.6%) CLL marrow samples. Wif-1 methylation occurred more frequently in
      patients with advanced age (p = 0.059) but there was no correlation between Wif-1
      methylation and sex, lymphocyte count and Rai stage at diagnosis. In conclusion,
      Wif-1 is infrequently methylated in CLL. Other factors leading to activation of
      the Wnt pathway warrant further study.

PMID- 16427697
TI  - Effect of macrophage secretory products on elaboration of virulence factors by
      planktonic and biofilm cells of Pseudomonas aeruginosa.
AB  - Macrophages, which constitute the first line of defense, pour their secretions in
      the mileu following stimulation with pathogens. These secretory products,
      referred to as macrophage secretory products (MSPs), can influence ultimate
      outcome of an infection. In the present investigation, it was observed that
      different strains of Pseudomonas aeruginosa vary in their ability to stimulate
      macrophages leading to variability in generation of macrophage secretory
      products. Cytokine levels, reactive nitrogen intermediates and protein content of
      macrophage secretory products generated with biofilm cells of P. aeruginosa was
      found to be more as compared to their planktonic counterparts. The effect of
      macrophage secretory products produced in response to interaction of macrophages
      with P. aeruginosa on elaboration of virulence factors produced by planktonic and
      biofilm cell forms of this pathogen was assessed. Significant enhancement in
      growth and elaboration of all the virulence determinants by both the cell forms
      was observed when P. aeruginosa was grown in presence of supernatants with
      macrophage secretory products. Implications of these findings in relation to
      urinary tract infections induced by P. aeruginosa have been discussed.

PMID- 16427696
TI  - Induction of oxidative stress by arsenic in Clarias batrachus: involvement of
      peroxisomes.
AB  - Indian catfish, Clarias batrachus, were exposed to two nonlethal doses of arsenic
      for 10 days, which induced tissue lipid peroxidation, increased the ratio of
      oxidized to reduced glutathione and produced excess H(2)O(2) within 1-2 days of
      exposure. Furthermore, arsenic treatment increased the activity of antioxidant
      enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and
      catalase but decreased glutathione reductase (GR) activity within a day of
      exposure, indicating the generation of oxidative stress in fish at an early
      stage. Reversibility of these arsenic-induced responses by pretreatment with N
      acetylcysteine indicates that the oxidative stress was due to excess H(2)O(2)
      production, which was found to be partially contributed by altered H(2)O(2)
      metabolism in the peroxisomes. It is therefore concluded that peroxisomal
      H(2)O(2) metabolizing enzymes are potential targets of arsenic toxicity in C.
      batrachus.

PMID- 16427698
TI  - Angle closure in highly myopic eyes.
AB  - PURPOSE: Patients with angle-closure glaucoma and high myopia are uncommon. We
      evaluated the clinical characteristics of all patients with angle closure and
      high myopia in our database and propose possible mechanisms for angle closure in
      these atypical patients. DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: Our database of 17938 patients was searched for patients with
      myopia of spherical equivalent of more than -6.0 diopters and angle closure. Data
      recorded included age at time of initial consultation, gender, slit-lamp
      examination results, gonioscopy results, biometric parameters, ultrasound
      biomicroscopy results (from 1993 onward), clinical diagnosis, and therapy.
      RESULTS: Twenty patients (11 females, 9 males) were identified. Mean age at the
      time of consultation was 52.9+/-19.3 years. Angle-closure diagnoses included
      primary pupillary block (9 patients), pupillary block in an eye with keratoconus
      (1 patient), pupillary block secondary to a pupillary membrane associated with
      retinopathy of prematurity (1 patient), plateau iris configuration and syndrome
      (3 patients), phacomorphic glaucoma in Weill-Marchesani syndrome (2 patients),
      malignant glaucoma secondary to a scleral buckle (2 patients), miotic-induced
      angle closure (1 patient), and Marfan syndrome (1 patient). CONCLUSIONS: Angle
      closure can occur in eyes with high myopia. Causes of angle closure other than
      relative pupillary block are more common than in the general angle-closure
      glaucoma population. Careful gonioscopy accompanied by biometry and ultrasound
      biomicroscopy can lead to the correct diagnosis and individualized management in
      these eyes.

PMID- 16427699
TI  - Acanthamoeba keratitis: clinical characteristics and management.
AB  - OBJECTIVE: To review the clinical characteristics, treatment, and outcome of
      patients with Acanthamoeba keratitis (AK). DESIGN: Retrospective, noncomparative,
      interventional case series. PARTICIPANTS: Twenty consecutive patients with AK
      were referred to the Beijing Tongren Hospital, Capital University of Medical
      Science, China. METHODS: Retrospective analysis of medical records from 20
      consecutive patients with AK between December 1, 1997 and March 30, 2003. Risk
      factors, laboratory investigations, clinical manifestations, treatments, and
      outcomes were analyzed. MAIN OUTCOME MEASURES: Best-corrected visual acuity
      (BCVA) at the end of follow-up. RESULTS: Of the 20 patients presented in this
      series, 12 patients were students and 6 were farmers. Risk factors included
      contact lens wear (12/20) and trauma (6/20). Corneal ulceration, diffuse stromal
      infiltration, and ring infiltration were the main clinical manifestations. The
      diagnosis of all patients was based on the laboratory investigation. Smear and
      culture positive specimens were 19 of 20 and 12 of 20, respectively. Images of
      cysts were demonstrated with confocal microscopy in 4 patients. Treatment was
      combined instillation of chlorhexidine (0.02%), neomycin (0.5%), metronidazole
      (0.4%), and/or lesion cauterization with chlorhexidine (1%), and corneal lesion
      debridement. The mean duration of therapy was 70 days (range, 18-150 days).
      Nineteen lesions healed with scar formation. The BCVA was better or equal to
      20/100 in 7 eyes. CONCLUSIONS: Early diagnosis of AK is the key challenge in
      clinical practice. The combined use of antiacanthamoeba agents, debridement, and
      cauterization may be a best choice of treatment for patients who are diagnosed
      early in the course of their disease.

PMID- 16427701
TI  - Conjunctival T-cell lymphoma: a clinicopathologic case report.
AB  - OBJECTIVE: To report a patient with conjunctival T-cell lymphoma, an extremely
      rare entity. DESIGN: Single case report. METHODS: Based on clinical examination,
      an excisional biopsy and immunostaining were performed on the conjunctival
      lesion. For management, we excised and performed triple freeze-thaw cryotherapy
      to the involved area, and we consulted the oncology service. MAIN OUTCOME
      MEASURES: T-cell and B-cell markers, and clinical examination of the lesion.
      RESULTS: Both examination and laboratory assessment revealed no evidence of
      systemic involvement. Conjunctival biopsy showed expansion of the substantia
      propria with an infiltrate of chronic inflammatory cells (including lymphocytes,
      plasma cells, and eosinophils), and prominent lymphocyte exocytosis with reactive
      epithelial changes. The CD-45 RO (T-cell marker) was strongly positive, whereas
      the CD-20 (B-cell marker) was negative. The T-cell receptor gene rearrangement
      was positive with beta clonality, confirming the diagnosis of T-cell lymphoma.
      CONCLUSIONS: T-cell lymphoma is a rare but possible diagnosis of gelatinous
      conjunctival lesions. The oncology consultants were reluctant to treat the
      patient with systemic chemotherapy or radiation because extraconjunctival
      extension could never be documented. The answer to the question of what is the
      most appropriate treatment for conjunctival T-cell lymphoma remains unknown.

PMID- 16427700
TI  - Alcohol delamination of the corneal epithelium: an alternative in the management
      of recurrent corneal erosions.
AB  - PURPOSE: To investigate the efficacy of alcohol delamination in the management of
      recurrent corneal erosions (RCEs). DESIGN: Prospective single-center consecutive
      descriptive case series. PARTICIPANTS: Twelve patients with RCEs who did not
      respond to conservative management were treated with alcohol delamination.
      METHODS: A consecutive case series of 12 patients with RCEs who did not respond
      to conservative management were treated by alcohol delamination. A pain score was
      generated based on a visual analog scale of pain intensity. The duration of pain
      and frequency were also recorded. Patients were followed up at 1 week, 4 weeks, 3
      months, 6 months, and 1 year and then at yearly intervals and monitored for
      recurrence of symptoms and corneal morphology. The removed epithelial sheet was
      examined by electron microscopy in 4 patients. INTERVENTION: The affected area of
      epithelium was peeled off after an application of 20% alcohol for 40 seconds
      under topical anesthesia. Eyes of patients were treated with an antibiotic and
      preservative-free artificial tear medication, and a bandage contact lens was
      inserted until epithelial healing was complete. MAIN OUTCOME MEASURES: Frequency
      of recurrence of erosions and duration and intensity of symptoms after alcohol
      delamination were studied. RESULTS: Eleven of the 12 eyes of patients had
      dramatic relief of symptoms over the follow-up period, ranging from 6 to 40
      months. Eight patients were symptom free, and 1 patient had 2 mild symptom
      episodes in the first posttreatment month before becoming symptom free. The
      average follow-up period was 23.5 months. There were no residual effects from the
      application of alcohol noted in any patient. Electron microscopy of removed
      epithelium showed features of the underlying pathology. The separation of the
      epithelium occurred at the interface of the subepithelial abnormal deposit and
      the surface of Bowman's zone. CONCLUSION: Alcohol delamination appears to be a
      novel, simple, inexpensive treatment for RCEs. Unlike other methods, the removed
      epithelium is available as a sheet that may be subjected to further examination,
      though some of the changes observed may reflect the effect of alcohol on the
      epithelium.

PMID- 16427702
TI  - The efficacy and tolerability of voriconazole in the treatment of chronic
      cavitary pulmonary aspergillosis.
AB  - Voriconazole is the second oral drug licensed for the treatment of aspergillosis.
      A retrospective non-comparative study was conducted in 16 patients with chronic
      cavitary pulmonary aspergillosis (CCPA) treated with voriconazole. All patients
      had failed or were intolerant of itraconazole. The duration of therapy varied
      from 3 days to 16.5 months. Eleven patients received at least 3 months of therapy
      with no significant adverse events. Overall seven (64%) patients had a response
      at 3 months as assessed by at least some fall in inflammatory markers, weight
      gain and reduction in pulmonary symptoms and two (18%) remained stable.
      Inflammatory markers improved in 5/11 (46%) with a mean fall in CRP of 0.08 mg/l
      and ESR of 12.8 mm/h. Aspergillus precipitins were quantitated by numbers of arcs
      and serum dilution and 11 (100%) showed improvement of at least one band or fall
      of titre. Total serum IgE was elevated (>200 IU/mL) in 5/11, and fell by a median
      of 118 kIU/l. Two patients failed therapy. Of the 17 patients, five (27%) had to
      discontinue therapy as a result of adverse events (three in under 1 week).
      Adverse events included erythematous rash (5), headaches (4), hepatotoxicity (3),
      photosensitive rash (3), retinal flashes (3) and neurological symptoms (3).
      Voriconazole is a useful alternative therapy for CCPA, with a response rate of
      64%, over 3 months, and continuing partial remission of disease for much longer
      periods.

PMID- 16427703
TI  - Clinical and psychometric characterization of depression in mixed mania: a report
      from the French National Cohort of 1090 manic patients.
AB  - BACKGROUND: Despite extensive research recently focused on mixed mania, it is
      uncertain as how best to define it clinically, psychometrically (which has major
      bearing on its prevalence), and the methodology needed for future research. This
      topic is also of historical interest, because Magnan (1890) [Magnan, V., 1890. La
      Folie Intermittente. G Masson, Paris.] suggested that "combined [mixed] states"
      linked Falret's "circular insanity" with Baillarger's "dual insanity" (both
      described in 1854). This work eventually led to the Kraepelinian synthesis of all
      manic, mixed, and depressive states into the unitary rubric of "manic-depressive
      insanity (1899/1921). METHOD: EPIMAN-II Thousand" (EPIMAN-II MILLE) is a French
      national collaborative study, which involved training 317 psychiatrists working
      in different sites representative of psychiatric practice in France. We recruited
      1090 patients hospitalized for acute DSM-IV mania. assessed at index admission by
      the following measures: the Mania Rating Scale (MRS), the Beigel-Murphy Scale
      (MSRS), a newly derived checklist of depressive symptoms least contaminated by
      mania, MADRS for severity of depression, and the SAPS for psychotic features.
      RESULTS: The rate of mixed mania, as defined by at least 2 depressive symptoms,
      was 30%. Even with this broad definition, we found significantly higher female
      representation. This clinical sub-type of mania was characterized by high
      frequency of past diagnostic errors, particularly those of anxiety and
      personality disorders. Refined definition of co-exiting depression was obtained
      from an abbreviated version of the MADRS (6 items), with distinct "emotional
      cognitive" symptoms, and "psychomotor inhibition" factors, both of which were
      separable from an "irritable" factor linked to lability and poor judgment. Mixed
      mania was psychometrically best identified by a MADRS score of 6 (80%
      sensitivity, 94% specificity) and validated by a mixed polarity of first
      episodes, a higher rate of recurrence, psychotic features, and suicide attempts.
      LIMITATION: Cross-sectional study. CONCLUSIONS: The data deriving from EPIMAN,
      the largest and only national study ever conducted on mania, provide definitive
      characterization of the clinical and psychotic structure of mixed mania, which
      accounts for 1 out of 3 patients who present with mania. This figure is more
      accurate than higher rates reported in the literature because, in describing
      "mixity", we eliminated depressive features that could be contaminated by mania.
      Despite the prominent affective features described herein, the bipolar nature of
      mixed mania is often missed, with the result that these patients are diagnosed as
      having anxiety and/or personality disorders. It is of great public health
      significance for psychiatrists to recognize the bipolar nature of this condition
      that has been known as a major phase of manic-depressive illness since at least
      Magnan, a disciple of Falret and Baillarger.

PMID- 16427704
TI  - Pathophysiology of catalytic antibodies.
AB  - Immunoglobulins have initially been illustrated as proteins produced by the
      immune system for binding and neutralizing foreign molecules potentially harmful
      to the organism. The number of V(H), D(H), J(H), V(L) and J(L) genes that encode
      the variable regions of immunoglobulins and the junctional diversity that occurs
      at the time of somatic rearrangement determine the extent of the repertoire of
      antibodies that may be potentially produced by an organism. This potential
      repertoire includes antibodies the antigen binding site of which may recognize
      external as well as autologous antigens, or may structurally resemble the active
      site of enzymes and be endowed with enzymatic activity. Under physiological
      conditions, B cell clones that produce antibodies naturally endowed with
      catalytic activity are negatively regulated and subjected to apoptosis. Catalytic
      antibodies are expressed only following active immunization, or if the
      physiological regulatory mechanisms that control the expression of catalytic
      antibody-producing B cell clones are perturbed, e.g. in the context of pregnancy
      or in the course of autoimmune diseases.

PMID- 16427705
TI  - Altered expression of Th1-type chemokine receptor CXCR3 on CD4+ T cells in
      myasthenia gravis patients.
AB  - The expression of chemokine receptors on peripheral blood lymphocytes and
      thymocytes of myasthenia gravis (MG) patients was analyzed before and after
      therapy with special reference to the thymic histopathology. Before therapy, MG
      patients showed reduced frequency of CD4+ T cells expressing T-helper1 (Th1) type
      chemokine receptor CXCR3, with a significantly lower frequency in the thymoma
      group than in the thymic hyperplasia group, while the frequencies of CXCR3
      positive CD8+ T cells remained normal irrespective of the thymic pathology. Both
      CD4+ cells and CD8+ cells of the hyperplasia group showed significantly increased
      expression of CCR1 on the cells followed by a reduction to the control level
      after therapy. No significant changes in the frequencies of CCR2, CCR3, CCR4, and
      CCR5 were observed in either MG group. There was a significant inverse
      correlation between the percentage of CXCR3-positive CD4+ T cells and the disease
      severity assessed with the MGFA scale (Fig. 1, r=-0.55, p=0.0047). The CXCR3
      expression on CD4+ cells was increased toward the control level long after the
      initiation of therapy. The thymomas showed significantly higher percentages of
      CXCR3-positive CD4+CD8- single positive cells than the control thymuses and,
      though not significantly, the hyperplastic thymuses also showed higher
      percentages. These results indicated that Th1-type chemokine signalings were
      altered in the MG patients, particularly those with thymoma, and that the thymus
      and thymoma are important sites of Th1-type reactions. The slow clinical
      improvement of MG symptoms after treatment may be explained partly by the gradual
      normalization of CXCR3-mediated signaling.

PMID- 16427706
TI  - Oriented immobilisation of engineered single-chain antibodies to develop
      biosensors for virus detection.
AB  - Single chain variable fragment (scFv) molecules were selected from a synthetic
      phage display library then cloned into a generic vector for expression of the
      scFv fused to the light chain constant domain of human immunoglobulin with a C
      terminal cysteine residue (scFvC(L)cys). A heterobifunctional maleimide linker
      was synthesised and a strategy for functionalization of gold with the scFvC(L)cys
      fusion proteins elaborated. Successful covalent attachment of functional
      scFvC(L)cys was demonstrated using a surface plasmon resonance-based sensor. The
      results showed that the immobilised scFvC(L)cys molecules were functional and
      specific binding curves (with response relative to the concentration of virus
      antigen) were obtained over more than 25 cycles of binding and dissociation. ScFv
      molecules lacking the C-terminal cysteine performed poorly in similar
      experiments. The work demonstrates the feasibility of using simple scFv selection
      and cloning procedures combined with oriented immobilisation of scFvC(L)cys
      fusion proteins for robust antigen sensing surfaces in immunosensor or other
      biotechnological applications.

PMID- 16427707
TI  - Sapovirus detection by quantitative real-time RT-PCR in clinical stool specimens.
AB  - Sapovirus (SV) is one of the major causative agents of viral gastroenteritis
      affecting all age groups worldwide. A new method for the quantitative detection
      of SV from clinical stool specimens by real-time reverse transcription-polymerase
      chain reaction (RT-PCR) based on TaqMan MGB technology was described. Primers and
      probe were designed to target the RNA-dependent RNA polymerase/capsid genes
      junction. Performance of the newly developed assay was validated against a panel
      of 244 clinical stool specimens collected for patients with gastroenteritis. SV
      was detected in eight (3.3%) specimens. Phylogenetic analysis of the positive
      isolates suggested that the assay could detect at least SV genogroups I, II and
      IV. In addition, the assay had an increased detection rate compared with a widely
      used conventional RT-PCR assay. Quantitative analysis showed that the assay could
      detect as low as 10 copies of viral cDNA per reaction. No cross-reactivity with
      norovirus and rotavirus was observed. In conclusion, the assay is a sensitive and
      specific method for the detection of SV from clinical stool specimens.

PMID- 16427709
TI  - Gene transcription in trypanosomes.
AB  - Trypanosoma brucei and the other members of the trypanosomatid family of
      parasitic protozoa, contain an unusual RNA polymerase II enzyme, uncoordinated
      mRNA 5' capping and transcription initiation events, and most likely contain an
      abridged set of transcription factors. Pre-mRNA start sites remain elusive. In
      addition, two important life cycle stage-specific mRNAs are transcribed by RNA
      polymerase I. This review interprets these unusual transcription traits in the
      context of parasite biology.

PMID- 16427708
TI  - Potential role of a CD36-like class B scavenger receptor in the binding of
      modified low-density lipoprotein (acLDL) to the tegumental surface of Schistosoma
      mansoni sporocysts.
AB  - Previous studies have documented the binding of low density lipoproteins (LDLs)
      to the tegumental surface of the mammalian stage of the human blood fluke
      Schistosoma mansoni, and that such binding may be functioning in the acquisition
      of host lipids for nutritional and/or immune evasion purposes. To determine if
      the intramolluscan mother sporocyst stage of S. mansoni also possess the ability
      to acquire exogenous LDL, live sporocysts, derived by in vitro transformation of
      isolated miracidia, were treated with DiI-labeled LDL (LDL-DiI) or acetylated LDL
      (acLDL-DiI). Sporocysts markedly differed in their binding, exhibiting strong
      labeling at the tegumental surface with acLDL-DiI, and only weak binding of LDL
      DiI. As scavenger receptors (SRs) are known to selectively bind modified
      (acetylated or oxidized) LDL and other polyanionic molecules, various potential
      ligands of known SRs were used in an acLDL-DiI binding inhibition assay.
      Significant acLDL-DiI binding inhibition was observed for fucoidan, polyinosinic
      acid and dextran sulfate, but not for polycytidylic acid and dextran, a binding
      inhibition pattern consistent with SR class A or C activity. From a S. mansoni
      EST sequence, we cloned a scavenger receptor homologue from sporocyst cDNA that
      encoded a protein with 31% amino acid sequence identity and 50% similarity to a
      SR class B (SRB) molecule, belonging to the CD36 superfamily. Using an RNA
      interference assay, treatment of miracidia with a 517bp double-stranded RNA of
      the S. mansoni SRB gene resulted in a significant and specific knockdown (60-70%)
      of SRB transcript levels in sporocysts after 6 days of dsRNA exposure and was
      associated with a significant reduction in acLDL-DiI binding to sporocysts at 8
      and 10 days post-dsRNA incubation. There also was a time-dependent decrease in
      sporocyst length following dsRNA treatments. The functional linkage of acLDL
      binding to the cloned SRB-like S. mansoni gene using RNA interference (RNAi)
      suggests a possible role of the tegumental SRB-like protein as a receptor for
      modified LDL. Inhibition of sporocyst growth also indicates a potential
      involvement of this SR homologue in some aspect of larval growth and/or
      development.

PMID- 16427710
TI  - Adrenal pheochromocytoma associated with transient hyperreninemia.

PMID- 16427711
TI  - Factors affecting sensitivity and specificity of pooled-sample testing for
      diagnosis of low prevalence infections.
AB  - Testing of pooled samples has been proposed as a low-cost alternative for
      diagnostic screening and surveillance for infectious agents in situations where
      the prevalence of infection is low and most samples can be expected to test
      negative. The present study extends our previous work in pooled-sample testing
      (PST) to evaluate effects of the following factors on the overall PST sensitivity
      (SE(k)) and specificity (SP(k)): dilution (pool size), cross-contamination, and
      cross-reaction. A probabilistic model, in conjunction with Monte Carlo
      simulations, was used to calculate SE(k) and SP(k), as applied to detection of
      bovine viral diarrhea virus (BVDV) persistently infected (PI) animals using RT
      PCR. For an average prevalence of BVDV PI of 0.01 and viremia in each animal
      between 10(2) and 10(7)virusparticles/mL, the pool size associated with the
      lowest number of tests, and lowest cost, corresponded to eight samples/pool.
      However, the least-cost pool size (lowest number of tests) was associated with a
      SE(k) of 0.90 (0.75-1), which corresponded to a decrease of 0.04, relative to the
      assay sensitivity for a single sample. The SP(k) for the same pool size,
      considering the effect of detection of BVDV acutely infected animals and cross
      contamination as source of false positive results, was 0.90 (0.85-0.95). The
      effect of a hypothetical cross-reacting agent was to markedly decrease SP(k),
      especially as the prevalence of the cross-reacting agent increased. For a pool
      size of eight samples and a prevalence of the cross-reacting agent of 0.3, SP(k)
      ranged from 0.67 to 0.86, depending on the probability that the assay would
      detect the cross-reacting agent. The methods presented offer a means of
      evaluating and understanding the various factors that can influence overall
      accuracy of PST procedures.

PMID- 16427712
TI  - Detection of Mycobacterium tuberculosis complex with Real Time PCR: comparison of
      different primer-probe sets based on the IS6110 element.
AB  - The sensitivity and specificity to detect Mycobacterium tuberculosis complex of
      four Real Time PCR primer-probe sets was compared. Three sets targeted nearly the
      same location on the IS6110 sequence and set 4 targeted a location 200 bp
      downstream on IS6110. Real Time PCR's with sets 1, 2 and 3 were carried out with
      co-amplification of a modified target as an internal amplification control. By
      testing identical DNA samples it was shown that small changes in primer and probe
      sequences result in differences in the performance of the assays, regarding
      analytical sensitivity and specificity.

PMID- 16427713
TI  - The influence of autonomic arousal and semantic relatedness on memory for
      emotional words.
AB  - Increased memory for emotional stimuli is a well-documented phenomenon. Emotional
      arousal during the encoding of a stimulus is one mediator of this memory
      enhancement. Other variables such as semantic relatedness also play a role in the
      enhanced memory for emotional stimuli, especially for verbal stimuli. Research
      has not addressed the contributions of emotional arousal, indexed by self-report
      and autonomic measures, and semantic relatedness on memory performance. Twenty
      young adults (10 women) were presented neutral-unrelated words, school-related
      words, moderately arousing emotional words, and highly arousing taboo words while
      heart rate and skin conductance were measured. Memory was tested with free recall
      and recognition tests. Results showed that taboo words, which were both
      semantically related and high arousal were remembered best. School-related words,
      which were high on semantic relatedness but low on arousal, were remembered
      better than the moderately arousing emotional words and semantically unrelated
      neutral words. Psychophysiological responses showed that within the moderately
      arousing emotional and neutral word groups, those words eliciting greater
      autonomic activity were better remembered than words that did not elicit such
      activity. These results demonstrate additive effects of semantic relatedness and
      emotional arousal on memory. Relatedness confers an advantage to memory (as in
      the school-words), but the combination of relatedness and arousal (as in the
      taboo words) results in the best memory performance.

PMID- 16427714
TI  - The right hemisphere of sleeping infant perceives sentential prosody.
AB  - Behavioral studies proposed that prosodic information in speech sounds plays
      important roles for human infants to acquire their native languages. Here, we
      examined the neural basis of prosodic processing in 3-month-old infants. In order
      to obtain hemodynamic responses with high signal-to-noise ratio, we used near
      infrared optical topography in the infants while they were in quiet sleep. First,
      we observed bilateral activation under each of the normal and flattened speech
      conditions. The flattened speech sound was created by eliminating changes in the
      pitch contours of the original utterance. In a direct comparison between the two
      conditions, the right temporoparietal region showed more prominent activation to
      normal speech sounds than to flattened speech sounds. This result demonstrates
      that the localized region of the right hemisphere in 3-month-old infant is
      involved in the processing of pitch contours. Our findings suggest that prosodic
      processing in the right hemisphere may facilitate the acquisition of lexical or
      syntactic knowledge in the early stages of language development.

PMID- 16427715
TI  - Effects of GABAB-agonist on rat hypothalamic neurons: functional antagonism with
      mu-receptor agonist.
AB  - Extracellular and whole-cell patch clamp recordings were made from neurons in
      slices of the preoptic area/anterior hypothalamus (PO/AH) of rats, to investigate
      the effects of the GABA(B)-receptor agonist baclofen on neuronal response
      characteristics, as well as its interactions with mu-opioid receptor agonist PL
      017 on the level of central temperature controller. Baclofen decreased tonic
      activity (firing rate) in all types of neurons, but increased temperature
      sensitivity (temperature coefficient, TC) in warm-sensitive neurons. The decrease
      in firing rate during baclofen application was accompanied with significant
      membrane hyperpolarization and decrease of input resistances. The tonic activity
      (in all type of PO/AH neurons), as well as the temperature sensitivity (in warm
      sensitive neurons), were inhibited by mu-opioid receptor agonist PL-017.
      Remarkably, the effect on temperature sensitivity was abolished and absence of
      synergism in regard to firing rate decrease occurred, when baclofen and PL-017
      were applied simultaneously. Our results are step of understanding the
      complicated mechanisms of action of neurotransmitters and their interactions on
      the level of central temperature controller-the neurons of the PO/AH.

PMID- 16427716
TI  - Occult hepatitis B virus infection and transfusion.

PMID- 16427717
TI  - Place of residence and distance to medical care influence the diagnosis of
      hepatitis C: a population-based study.
AB  - BACKGROUND/AIMS: In France, geographic access to medical care may affect the
      diagnosis of hepatitis C. The aims of this study were to compare the detection
      rates of hepatitis C in urban and rural areas after adjusting for distance to
      medical care, and evaluating the impact of the place of residence on patients'
      clinical characteristics. METHODS: Between 1994 and 2001, 1938 newly detected
      cases were recorded in a French population of 1,005,817 inhabitants. Age and sex
      adjusted detection rates for 10(5) inhabitants were estimated for urban and rural
      areas and for classes of distance to the nearest practitioner. RESULTS: Detection
      rates were lower in rural than in urban areas [14.1, (95CI: 12.5-15.7) versus
      24.7, (95CI: 23.5-26.0)] and decreased as the distance to the general
      practitioner increased [27.0, (95CI: 25.5-28.4) versus 13.7, (95CI: 12.1-15.3)
      for a cutoff value of 1.5 km]. In multivariate analyses, detection rates were
      only influenced by the distance to general practitioner. Hepatocellular carcinoma
      at diagnosis was more frequent among rural than among urban patients (adjusted OR
      = 2.28, 95CI: 0.97-5.39, P = 0.059). CONCLUSIONS: A poorer geographic access to
      care explained the lower detection of hepatitis C in rural areas. Hepatocellular
      carcinoma was more frequent in rural patients. It may result from later detection
      and/or involvement of environmental factors on hepatocarcinogenesis.

PMID- 16427718
TI  - Acute hepatitis associated with the use of green tea infusions.

PMID- 16427719
TI  - Liver transplantation for Budd-Chiari syndrome: A European study on 248 patients
      from 51 centres.
AB  - BACKGROUND/AIMS: The results of liver transplantation for Budd-Chiari syndrome
      (BCS) are poorly known and the role and timing of the procedure are still
      controversial. The aim of this study was to investigate the results of
      transplantation for BCS, focusing on overall outcome, on prognostic factors and
      on the impact of the underlying disease. METHODS: An enquiry on 248 patients
      representing 84% of the patients transplanted for BCS in the European Liver
      Transplantation Registry between 1988 and 1999. RESULTS: Of the 248 patients,
      70.4% were female and 29.6% male. The mean age was 35.7 years. The overall
      actuarial survival was 76% at 1 year, 71% at 5 years and 68% at 10 years. 77% of
      deaths occurred in the first 3 months: 47% were due to infection and multiple
      organ failure, and 18% to graft failure or hepatic artery thrombosis. Late
      mortality (>1 year) occurred in nine patients, due to BCS recurrence in four of
      them. The only pre-transplant predictors of mortality on multivariate analysis
      (Cox) were impaired renal function and a history of a shunt. CONCLUSIONS: Liver
      transplantation for BCS is an effective treatment, irrespective of the underlying
      cause, and should be considered before renal failure occurs.

PMID- 16427720
TI  - Risk scores in cirrhotic patients: From non-transplant surgery to transplantation
      and back.

PMID- 16427721
TI  - Applicability of the Transient Storage Model to the hyporheic exchange of metals.
AB  - Stream-subsurface exchange results from a complex ensemble of transport
      mechanisms that require different modeling approaches. Field and laboratory
      experiments show that advective exchange through the underlying sediments is an
      important mechanism of solutes transport and storage in riverine systems. Here,
      Transient Storage Model parameters are obtained for reactive solute exchange
      driven by bedform-induced advection. Consideration of exchange induced by this
      single mechanism allows specific relationships between model parameters and
      system properties like solute reactivity to be identified. This work shows that
      when a simplified model like the Transient Storage Model is applied to analyze
      metal storage in river sediments, particular attention must be devoted to the
      choice of modeling parameters.

PMID- 16427722
TI  - Vessel ultrastructure in APP23 transgenic mice after passive anti-Abeta
      immunotherapy and subsequent intracerebral hemorrhage.
AB  - Passive immunization of amyloid precursor protein (APP) transgenic mice with anti
      amyloid beta (Abeta) antibodies was shown to reduce Abeta-deposition in brain and
      to improve cognition. However, immunotherapy may also be accompanied by a
      significant increase in the frequency of intracerebral hemorrhages. Because
      hemorrhages are associated with amyloid-laden vessels, this raises the question
      whether high concentrations of anti-Abeta antibodies may directly or indirectly
      lead to a structural destabilization of the vessel wall. To address this point,
      transmission electron microscopy was performed and the ultrastructure of bleeding
      and non-bleeding vessels in immunized and non-immunized APP23 transgenic animals
      was analyzed. To localize bleeding vessels, hemosiderin-positive macrophages were
      visualized by pre-embedding Perl's Berlin Blue histochemistry. Vessels were
      analyzed morphologically, anomalies evaluated and quantified. Bleeding vessels
      were, furthermore, reconstructed in three dimensions to analyze the spatial
      distribution of amyloid deposits and other pathological changes of the vessel
      wall. This in-depth morphological analysis revealed that bleeding vessels in
      immunized as well as in non-immunized APP23 mice were surrounded by a higher
      number of macrophages compared to non-bleeding vessels in the same animals.
      However, no differences in the number of macrophages or other structural
      parameters, such as amyloid deposition, were observed between bleeding vessels of
      immunized and non-immunized mice. No pathologies which may indicate impending
      bleeding were observed in the vascular wall of non-bleeding vessels. We conclude,
      that the increased hemorrhage frequency observed after passive immunization with
      anti-Abeta antibodies does not lead to overt structural changes in the vessel
      wall of APP23 transgenic mice. Minor structural alterations of the vessel wall,
      however, cannot be excluded due to the sample size of our study and the high
      complexity of the three-dimensional vessel wall ultrastructure.

PMID- 16427723
TI  - Distribution of gamma-ray emitting radionuclides in the environment of Burullus
      Lake: I. Soils and vegetations.
AB  - The concentrations and distribution of gamma-ray emitting isotopes in Burullus
      Lake were investigated with the aim of evaluating the environmental
      radioactivity. Particularly in wetlands, natural properties of the environment
      can cause the actual inventory to be different from the activity originally
      deposited. The mean concentrations of (226)Ra, (232)Th and (40)K were 14.3, 15.5
      and 224 Bq/kg, respectively, in the coastal soils. On the other hand, soil
      samples from the islands had mean concentrations of 13.5, 17.4 and 341 Bq/kg for
      (226)Ra, (232)Th and (40)K, respectively. Samples from coast and islands show
      evidence of possible transfer and accumulation of the (137)Cs radionuclide. The
      mean (137)Cs activity concentrations in the soil samples were 1.2 and 15.1 Bq/kg
      in the coast and islands, respectively. The vertical migration of (137)Cs was
      studied based on its content in the consequently located three soil layers down
      to 30 cm depth. The radium equivalent, dose rate in air and annual dose
      equivalent from the terrestrial natural gamma-radiation were evaluated. The mean
      activity concentrations of the gamma-ray emitting radionuclides in vegetation
      were relatively low.

PMID- 16427724
TI  - The effect of mitek anchor insertion angle to attachment of FDP avulsion
      injuries.
AB  - Flexor digitorum profundus (FDP) tendon avulsions, although uncommon, are not
      infrequent injuries. A widely accepted method of treating Type 1 FDP avulsions is
      a pullout suture tied over a button on the nail plate. The external dorsal button
      is often a source of inconvenience for the patient. Potential risks associated
      with button use include nail plate deformities, nail fold necrosis and infections
      tracking along the sutures. The use of small suture anchors provides a
      satisfactory alternative, because buried fixation avoids these potential
      complications. This in vitro, biomechanical study examined the influence of the
      anchor orientation on the properties of the repaired FDP tendon using human
      cadavers.

PMID- 16427725
TI  - Extravasation of calcium solution leading to calcinosis cutis surrounding the
      dorsal cutaneous branch of the ulnar nerve.
AB  - A case of calcinosis cutis caused by calcium extravasation around the wrist is
      presented. During excision, the lesion was seen to be surrounding the dorsal
      branch of the ulnar nerve. The possibility of peripheral nerve involvement in
      extravasation injuries is emphasized.

PMID- 16427726
TI  - Interdigital pilonidal sinus in a hairdresser.
AB  - Pilonidal sinus of the interdigital web space of the hand is a rare occupational
      disease which occurs in hairdressers and professionals working with animals. This
      paper reports such a sinus in the hand of a male hairdresser and reviews the
      treatment of this condition.

PMID- 16427727
TI  - Changing contaminant mobility in a dredged canal sediment during a three-year
      phytoremediation trial.
AB  - Metal mobility and degradation of organic pollutants were investigated in a
      contaminated canal sediment in NW England. Sediment was dredged and exposed above
      the water surface, planted with multiple taxa of Salix, Populus and Alnus and
      monitored over 32 months. Short-term metal fractionation and phytotoxicity during
      sediment oxidation were also evaluated in separate laboratory studies. Zinc and
      Pb redistributed into more mobile fractions, which increased toxicity of the
      sediment to plants in the laboratory. In contrast, at the canal site, mobility of
      most elements decreased and total concentrations of Zn, Pb, Cu and Cd fell.
      Petroleum hydrocarbon concentrations decreased, but the tree-planted treatments
      appeared less effective at reducing PAH concentrations than treatments colonised
      by invasive plants. Tree survivorship decreased over time, suggesting increasing
      phytotoxicity of the exposed sediment in the longer term. Trees provided little
      benefit in terms of sediment remediation. Options for future management of the
      sediment are evaluated.

PMID- 16427729
TI  - Mechanisms of action of current and potential pharmacotherapies of obsessive
      compulsive disorder.
AB  - A significant body of evidence documented that the orbitofrontal cortex (OFC) and
      the head of caudate nucleus are involved in the mediation of obsessive-compulsive
      disorder (OCD) symptoms. Potent serotonin (5-HT) reuptake inhibitors (SRIs) are
      the only antidepressant agents thus far shown to be effective in the treatment of
      OCD. The present review summarizes information on 5-HT release and the adaptive
      changes in pre- and postsynaptic 5-HT receptors sensitivity induced by SRI
      treatment in rat and guinea pig structures involved in OCD. It emphasizes that
      the time course for the occurrence of increased 5-HT release and terminal 5-HT1D
      desensitization is congruent with the delayed therapeutic response to SRI in OCD.
      In addition, a greater dose of SRI inducing a greater degree of reuptake
      inhibition may play an essential role in this phenomenon. This is consistent with
      the common clinical observation that high doses of SRIs are sometimes necessary
      to obtain an anti-OCD effect, and with the results of some fixed-dose double
      blind trials showing a dose-dependent therapeutic effect of SRIs. It is
      hypothesized that enhanced 5-HT release in the OFC is mediated by the activation
      of normosensitive postsynaptic 5-HT2-like receptors and underlies the therapeutic
      action of SRI in OCD. This is supported by the beneficial effect of some
      hallucinogens with 5-HT2 agonistic properties in obtaining a more rapid
      therapeutic response. Finally, based on this knowledge, new strategies aimed at
      producing more rapid, effective and safe anti-OCD drugs, such as a selective
      action on terminal 5-HT1D receptors, on 5-HT2 receptors as well as on the
      glutamate system, are discussed.

PMID- 16427728
TI  - Centralized drug review processes: are they fair?
AB  - Numerous countries have implemented centralized drug review processes to assist
      in making drug coverage decisions. In addition to examining the final
      recommendations of these bodies, it is also important to ensure fairness in
      decision making. Accountability for reasonableness is an ethics-based framework
      for examining the fairness of priority setting processes. The objective of this
      study was to assess the fairness of four internationally established centralized
      drug review processes using accountability for reasonableness. Semi-structured
      telephone interviews were conducted with stakeholders in Canada, New Zealand,
      Australia and the UK (n=16). Participants were asked to evaluate their country's
      centralized drug review process against the four conditions of accountability for
      reasonableness. Each centralized drug review process satisfied at least one of
      the four ethical conditions, but none satisfied all four conditions. All
      participants viewed transparency as critical to both the legitimacy and fairness
      of centralized drug review processes. Additional strides need to be made in each
      of the four countries under study to improve the fairness of their centralized
      drug review processes. Ideally, a fair priority setting process should foster
      constructive stakeholder engagement and enhance the legitimacy of decisions made
      in assessing pharmaceutical products for funding. As policy makers are under
      increasing scrutiny in allocating limited resources, fair process should be seen
      as a critical component of such activity. This study represents the first attempt
      to conduct an international comparison of the fairness of centralized drug review
      agencies in the eyes of participating stakeholders.

PMID- 16427730
TI  - Ex vivo measurement of cell apoptosis and proliferation in breast tissue of
      healthy women: influence of age and steroid status. An exploratory study.

PMID- 16427731
TI  - Polymorphisms of interleukin-6, hepatic lipase and calpain-10 genes, and
      preeclampsia.
AB  - OBJECTIVE: We determined whether single nucleotide polymorphisms (SNPs) in
      interleukin-6 (IL-6), hepatic lipase (HL) and calpain-10 (CAPN-10) genes
      contribute to susceptibility to develop preeclampsia. STUDY DESIGN: The study
      involved 133 preeclamptic and 115 healthy pregnant women who were genotyped for
      the C-174G polymorphism in the IL-6 gene, the G-250A polymorphism in the HL gene
      and SNP 43 (G/A) in the CAPN-10 gene. The chi2-test was used to assess genotype
      and allele frequency differences between the preeclamptic and control groups.
      RESULTS: No significant differences were detected in genotype and allele
      distributions of the C-174G polymorphism in the IL-6 gene, between the
      preeclampsia and control groups (p=0.98 and 0.85, respectively). With respect to
      the G-250A polymorphism in the HL gene, the genotype and allele distributions
      were similar in both groups (p=0.64 and 0.48, respectively). The genotype and
      allele distributions of SNP 43 in the CAPN-10 gene also showed no statistical
      differences in the preeclampsia and control groups (p=0.73 and 0.45,
      respectively). CONCLUSIONS: The C-174G polymorphism in the IL-6 gene, the G-250A
      polymorphism in the HL gene and SNP 43 (G/A) in the CAPN-10 gene are unlikely to
      be major genetic factors predisposing Finnish women to preeclampsia.

PMID- 16427732
TI  - Mechanism of beta-purothionin antimicrobial peptide inhibition by metal ions:
      molecular dynamics simulation study.
AB  - Wheat beta-purothionin is a highly potent antimicrobial peptide which, however,
      is inactivated by metal ions. The key structural properties and mechanisms of
      inhibition of beta-purothionin were investigated for the first time using
      unconstrained molecular dynamics simulations in explicit water. A series of
      simulations were performed to determine effects of temperature and the metal
      ions. Analyses of the unconstrained simulations allowed the experimentally
      unavailable structural and dynamic details to be unambiguously examined. The
      global fold and the alpha1 helix of beta-purothionin are thermally stable and not
      affected by metal ions. In contrast, the alpha2 helix unfolds with shift of
      temperature from 300 K and in the presence of metal ions. The network of
      conserved residues including Arg30 and Lys5 is sensitive to environmental changes
      and triggers unfolding. Loop regions display high flexibility and elevated
      dynamics, but are affected by metal ions. Our study provides insights into the
      mechanism of metal ion-based inhibition.

PMID- 16427733
TI  - Quantum-like brain: "Interference of minds".
AB  - We present a contextualist statistical realistic model for quantum-like
      representations in physics, cognitive science, and psychology. We apply this
      model to describe cognitive experiments to check quantum-like structures of
      mental processes. The crucial role is played by interference of probabilities for
      mental observables. Recently one such experiment based on recognition of images
      was performed. This experiment confirmed our prediction on the quantum-like
      behavior of mind. In our approach "quantumness of mind" has no direct relation to
      the fact that the brain (as any physical body) is composed of quantum particles.
      We invented a new terminology "quantum-like (QL) mind." Cognitive QL-behavior is
      characterized by a nonzero coefficient of interference lambda. This coefficient
      can be found on the basis of statistical data. There are predicted not only cos
      theta-interference of probabilities, but also hyperbolic cosh theta-interference.
      This interference was never observed for physical systems, but we could not
      exclude this possibility for cognitive systems. We propose a model of brain
      functioning as a QL-computer (there is a discussion on the difference between
      quantum and QL computers).

PMID- 16427734
TI  - GSTT1 and M1 polymorphisms in Hurthle thyroid cancer patients.
AB  - Glutathione S-transferases (GST) are an important part of cell defense against
      numerous genotoxic compounds and ROS. In order to test the possibility of
      association between the GSTT1 and M1 null allele variant, and the risk of TCO
      (thyroid carcinoma with cell oxyphilia), a case-control study was carried out.
      The rationale for our study was that according to the important roles of GST
      enzymes in cells and association of GST null genotypes with many types of tumors,
      inactivating polymorphisms may be genetic susceptibility factors in the etiology
      of oxyphilic thyroid tumors characterized by mitochondrial dysfunction, increased
      ROS production and resistance to chemio- and radio-therapy. We found the
      frequency of GSTT1 null genotype of 19.2% in cases and 15.7% in controls, with an
      adjusted odds ratio (OR) of 1.4 (95% confidence interval (CI), 0.70-2.81), and a
      frequency of GSTM1 null genotype of 59% in cases with oxyphilic tumors and of
      55.6% in controls (OR 1.24; 95% CI, 0.62-2.48), indicating that the GSTT1 and M1
      null genotypes do not increase the risk of development of oxyphilic tumors.

PMID- 16427735
TI  - Induction of hypoxia-inducible factor-1alpha overexpression by cobalt chloride
      enhances cellular resistance to photodynamic therapy.
AB  - Although photodynamic therapy (PDT) has been approved by regulatory agencies
      worldwide for the treatment of several oncologic and non-oncologic conditions,
      PDT-induced tissue hypoxia as a result of vascular damage and photochemical
      oxygen consumption limits the efficacy of this modality. This may largely be due
      to hypoxia-mediated angiogenesis via hypoxia-inducible factor-1alpha (HIF
      1alpha), a major transcription factor involved in angiogenesis, hematopoiesis and
      anaerobic energy metabolism. We hypothesized that hypoxia-induced HIF-1alpha
      overexpression may also lead to tumor cells resistant to PDT by favouring tumor
      cell proliferation. Human esophageal normal Het-1A and tumor KYSE-70 and KYSE-450
      cell lines were used in the present study. High-expression of HIF-1alpha induced
      in vitro by cobalt chloride (CoCl(2))-mediated chemical hypoxia mimic was clearly
      seen in the Het-1A cell line. In addition, cells treated with CoCl(2) were more
      resistant to 5-aminolevulinic acid (ALA)-mediated PDT than those without CoCl(2)
      treatment. The photosensitivity of the cells to ALA-PDT decreased with increasing
      HIF-1alpha expression by enhancing CoCl(2) concentrations. Moreover, transfection
      of the cells with anti-HIF-1alpha short interfering RNA (siRNA) knocked down the
      HIF-1alpha expression and restored the photosensitivity of the cells to ALA-PDT.
      However, the induction of HIF-1alpha expression by CoCl(2) was not indicated in
      both KYSE-70 and KYSE-450 cell lines, and no difference in cell survival was
      found after ALA-PDT in the presence and absence of CoCl(2). We thus conclude that
      high-expression of HIF-1alpha induced by CoCl(2) plays an important role in the
      resistance of the Het-1A cells to ALA-PDT. The present finding suggests that
      hypoxia-induced HIF-1alpha overexpression attenuates PDT efficacy through
      probably not only angiogenesis, but also cellular resistance to the modality. PDT
      in combination with anti-HIF-1alpha treatment may thus enhance the PDT efficacy.

PMID- 16427736
TI  - Induction of aberrant crypt foci in DNA mismatch repair-deficient mice by the
      food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP).
AB  - Disruption of the DNA mismatch repair (MMR) pathway results in elevated mutation
      rates, inappropriate survival of cells bearing DNA damage, and increased cancer
      risk. Relatively little is known about the impact of environmentally relevant
      carcinogens on cancer risk in individuals with MMR-deficiency. We evaluated the
      effect of MMR status (Mlh1(+/+) versus Mlh1(-/-)) on the carcinogenic potential
      of the cooked-meat mutagen, 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine
      (PhIP) in mice. PhIP exposure did not obviously increase lymphoma or small
      intestinal tumorigenesis in either Mlh1-deficient or -proficient mice. In
      contrast, the frequency of aberrant crypt foci (ACF), a preneoplastic biomarker
      for colon tumorigenesis, was increased by PhIP, and the increase due to PhIP was
      significantly greater in Mlh1(-/-) versus wild-type littermates. This apparent
      heightened susceptibility to induction of ACF parallels the previously reported
      hypermutability of Mlh1-deficient mice to PhIP and is consistent with the
      hypothesis that MMR-deficiency would increase the likelihood of PhIP-induced
      carcinogenic mutations. Further evaluation of the risk that consumption of
      heterocyclic amines may impart to MMR-deficient individuals therefore is
      warranted.

PMID- 16427737
TI  - Evidence of focal small-fiber axonal degeneration in complex regional pain
      syndrome-I (reflex sympathetic dystrophy).
AB  - CRPS-I consists of post-traumatic limb pain and autonomic abnormalities that
      continue despite apparent healing of inciting injuries. The cause of symptoms is
      unknown and objective findings are few, making diagnosis and treatment
      controversial, and research difficult. We tested the hypotheses that CRPS-I is
      caused by persistent minimal distal nerve injury (MDNI), specifically distal
      degeneration of small-diameter axons. These subserve pain and autonomic function.
      We studied 18 adults with IASP-defined CRPS-I affecting their arms or legs. We
      studied three sites on subjects' CRPS-affected and matching contralateral limb;
      the CRPS-affected site, and nearby unaffected ipsilateral and matching
      contralateral control sites. We performed quantitative mechanical and thermal
      sensory testing (QST) followed by quantitation of epidermal neurite densities
      within PGP9.5-immunolabeled skin biopsies. Seven adults with chronic leg pain,
      edema, disuse, and prior surgeries from trauma or osteoarthritis provided symptom
      matched controls. CRPS-I subjects had representative histories and symptoms.
      Medical procedures were unexpectedly frequently associated with CRPS onset. QST
      revealed mechanical allodynia (P<0.03) and heat-pain hyperalgesia (P<0.04) at the
      CRPS-affected site. Axonal densities were highly correlated between subjects'
      ipsilateral and contralateral control sites (r=0.97), but were diminished at the
      CRPS-affected sites of 17/18 subjects, on average by 29% (P<0.001). Overall,
      control subjects had no painful-site neurite reductions (P=1.00), suggesting that
      pain, disuse, or prior surgeries alone do not explain CRPS-associated neurite
      losses. These results support the hypothesis that CRPS-I is specifically
      associated with post-traumatic focal MDNI affecting nociceptive small-fibers.
      This type of nerve injury will remain undetected in most clinical settings.

PMID- 16427738
TI  - Cortical responses to pain in healthy individuals depends on pain
      catastrophizing.
AB  - The personal experience of pain is complex and depends on physiological and
      psychological factors. From this latter category, pain catastrophizing plays an
      important role in pain behavior and response. We aimed to determine the effect of
      pain catastrophizing on central nociceptive processing in healthy individuals.
      Functional MRI was performed during two pain intensity levels evoked by
      electrical median nerve stimulation in 22 healthy individuals. Pain
      catastrophizing scores were determined for all subjects. Pain catastrophizing was
      not related to activity in regions associated with sensory-discriminative aspects
      of pain, such as the primary or secondary somatosensory cortex. Instead, during
      mild pain, there was a relationship between catastrophizing and activity in
      cortical regions associated with affective, attention, and motor aspects of pain,
      including dorsolateral prefrontal, insula, rostral anterior cingulate, premotor,
      and parietal cortices. During more intense pain, prefrontal cortical regions
      implicated in the top-down modulation of pain were negatively correlated with
      catastrophizing. These findings can be viewed from the framework of an attention
      model of pain catastrophizing, whereby a cortical vigilance network is engaged
      during mild pain, but diminished prefrontal cortical modulation impedes
      disengaging from and suppressing pain during more intense pain. These findings
      may also implicate catastrophizing in the progression to or persistence of
      chronic pain.

PMID- 16427739
TI  - Molecular diagnosis and equine parasitology.
AB  - The future implementation of improved and sustainable control strategies for the
      major equine parasites will be dependent on a greater insight into their basic
      biology, pathogenicity and epidemiology together with an enhanced ability for
      accurate diagnosis. This paper will provide a review of the current molecular
      methods under development for the detection of equine parasites and their
      application to current scientific questions. In particular, the strongyles are
      recognised as important pathogens of horses and recent advances made in the study
      of this parasitic group at the single species level will be addressed. The
      ribosomal (r)DNA region of the parasite genome has been employed to distinguish
      between closely related species. Molecular probes designed to this target region
      were used in combination with PCR technology to allow the identification of
      individual species within mixed infections. They have been applied to all
      parasite stages to look at the role of individual species in natural infection,
      disease and drug resistance. Similar techniques have been developed to detect
      other equine parasites and these will also be discussed. Further opportunities
      for employing existing techniques and the need for new diagnostic tools will be
      highlighted.

PMID- 16427740
TI  - CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular
      smooth muscle cells via a PPARgamma ligand-like action.
AB  - Conjugated linoleic acids (CLAs) were reported to have anti-atherogenic
      properties in animal feeding experiments. In an attempt to elucidate the
      molecular mechanisms of these anti-atherogenic effects, the modulatory potential
      of CLA on cytokine-induced eicosanoid production from smooth muscle cells (SMCs),
      which contributes to the chronic inflammatory response associated with
      atherosclerosis, has been investigated in the present study. cis-9, trans-11 CLA
      and trans-10, cis-12 CLA were shown to reduce proportions of the eicosanoid
      precursor arachidonic acid in SMC total lipids and to inhibit cytokine-induced NF
      kappaB DNA-binding activity, mRNA levels of inducible enzymes involved in
      eicosanoid formation (cPLA2, COX-2, mPGES), and the production of the
      prostaglandins PGE2 and PGI2 by TNFalpha-stimulated SMCs in a dose-dependent
      manner. The effect of 50 micromol/L of either CLA isomer was as effective as 10
      micromol/L of the PPARgamma agonist troglitazone in terms of inhibiting the
      TNFalpha-stimulated eicosanoid production by SMCs. PPARgamma DNA-binding activity
      was increased by both CLA isomers compared to control cells. Moreover, it was
      shown that the PPARgamma antagonist T0070907 partially abrogated the inhibitory
      action of CLA isomers on cytokine-induced eicosanoid production and NF-kappaB DNA
      binding activity by vascular SMCs suggesting that PPARgamma signalling is at
      least partially involved in the action of CLA in human vascular SMCs. With
      respect to the effects of CLA on experimental atherosclerosis, our findings
      suggest that the anti-inflammatory effect of CLA is at least partially
      responsible for the anti-atherogenic effects of CLA observed in vivo.

PMID- 16427741
TI  - Ondansetron, prochlorperazine, and dexamethasone have similar effects on
      prevention of delayed chemotherapy-induced nausea and vomiting.

PMID- 16427743
TI  - Unilateral low-frequency stimulation of central piriform cortex delays seizure
      development induced by amygdaloid kindling in rats.
AB  - Low-frequency stimulation of the kindling site interferes with the course of
      kindling epileptogenesis. The present study examined the effect of unilateral low
      frequency stimulation of the central piriform cortex on seizure development
      induced by amygdaloid kindling in rats. The ipsilateral or contralateral central
      piriform cortex received low-frequency stimulation (15 min train of 0.1 ms pulses
      at 1 Hz and 50-150 muA) immediately after termination of once daily kindling
      stimulation (2 s train of 1 ms pulses at 60 Hz and 150-300 microA) in the right
      amygdala for 30 days. Low-frequency stimulation of either the ipsilateral or
      contralateral central piriform cortex significantly suppressed the progression of
      seizure stages and reduced afterdischarge duration throughout the course of
      amygdaloid kindling. The marked suppression induced by low-frequency stimulation
      of the central piriform cortex on either side was predominantly due to the
      significant retardation of progression from stage 0 to stage 1 and stage 3 to
      stage 4 seizures. In addition, the suppressive effect of low-frequency
      stimulation did not disappear when the stimulation was stopped; it could persist
      for at least 10 days. These findings indicate that brain areas other than the
      kindling focus, such as the central piriform cortex on both sides, can also be
      used as reasonable targets for low-frequency stimulation to retard seizure
      development induced by amygdaloid kindling. Secondly, like the ipsilateral
      central piriform cortex, the contralateral central piriform cortex may also
      participate in the progression and secondary generalization of focal seizures.
      The study suggests that unilateral low-frequency stimulation of the central
      piriform cortex may have a significant antiepileptogenic effect, and may be
      helpful for exploring effective and long-lasting therapies for human temporal
      lobe epilepsy.

PMID- 16427742
TI  - Spinal nerve ligation does not alter the expression or function of GABA(B)
      receptors in spinal cord and dorsal root ganglia of the rat.
AB  - Loss of GABA-mediated inhibition in the spinal cord is thought to mediate
      allodynia and spontaneous pain after nerve injury. Despite extensive
      investigation of GABA itself, relatively little is known about how nerve injury
      alters the receptors at which GABA acts. This study examined levels of GABA(B)
      receptor protein in the spinal cord dorsal horn, and in the L4 and L5 (lumbar
      designations) dorsal root ganglia one to 18 weeks after L5 spinal nerve ligation.
      Mechanical allodynia was maximal by 1 week and persisted at blunted levels for at
      least 18 weeks after injury. Spontaneous pain behaviors were evident for 6 weeks.
      Western blotting of dorsal horn detected two isoforms of the GABA(B(1)) subunit
      and a single GABA(B(2)) subunit. High levels of GABA(B(1a)) and low levels of
      GABA(B(1b)) protein were present in the dorsal root ganglia. However, GABA(B(2))
      protein was not detected in the dorsal root ganglia, consistent with the proposed
      existence of an atypical receptor composed of GABA(B(1)) homodimers. The levels
      of GABA(B(1a)), GABA(B(1b)), and GABA(B(2)) protein in the ipsilateral dorsal
      horn were unchanged at any time after injury. Immunohistochemical staining also
      did not detect a change in GABA(B(1)) or GABA(B(2)) subunits in dorsal horn
      segments having a robust loss of isolectin B4 staining. The levels of GABA(B(1a))
      protein were also unchanged in the L4 or L5 dorsal root ganglia at any time after
      spinal nerve ligation. Levels of GABA(B(2)) remained undetectable. Finally,
      baclofen-stimulated binding of guanosine-5'-(gamma-O-thio)triphosphate in dorsal
      horn did not differ between sham and ligated rats. Collectively, these results
      argue that a loss of GABA(B) receptor-mediated inhibition, particularly of
      central terminals of primary afferents, is unlikely to mediate the development or
      maintenance of allodynia or spontaneous pain behaviors after spinal nerve injury.

PMID- 16427744
TI  - Distribution of norepinephrine transporters in the non-human primate brain.
AB  - Noradrenergic terminals in the central nervous system are widespread; as such
      this system plays a role in varying functions such as stress responses,
      sympathetic regulation, attention, and memory processing, and its dysregulation
      has been linked to several pathologies. In particular, the norepinephrine
      transporter is a target in the brain of many therapeutic and abused drugs. We
      used the selective ligand [(3)H]nisoxetine, therefore, to describe
      autoradiographically the normal regional distribution of the norepinephrine
      transporter in the non-human primate central nervous system, thereby providing a
      baseline to which alterations due to pathological conditions can be compared. The
      norepinephrine transporter in the monkey brain was distributed heterogeneously,
      with highest levels occurring in the locus coeruleus complex and raphe nuclei,
      and moderate binding density in the hypothalamus, midline thalamic nuclei, bed
      nucleus of the stria terminalis, central nucleus of the amygdala, and brainstem
      nuclei such as the dorsal motor nucleus of the vagus and nucleus of the solitary
      tract. Low levels of binding to the norepinephrine transporter were measured in
      basolateral amygdala and cortical, hippocampal, and striatal regions. The
      distribution of the norepinephrine transporter in the non-human primate brain was
      comparable overall to that described in other species, however disparities exist
      between the rodent and the monkey in brain regions that play a role in such
      critical processes as memory and learning. The differences in such areas point to
      the possibility of important functional differences in noradrenergic information
      processing across species, and suggest the use of caution in applying findings
      made in the rodent to the human condition.

PMID- 16427745
TI  - Effect of cognitive behavior therapy on smokers' compensatory coping skills.
AB  - Cognitive behavior therapy for depression has been adapted for use in cigarette
      smoking cessation groups. CBT appears to be an effective treatment, though
      results are mixed as to whether it is especially helpful for smokers vulnerable
      to depression, and little is known about what mediates its effects. Based on the
      hypothesis that CBT works by way of teaching compensatory skills for coping with
      negative thinking and emotions, this study compared CBT with a time-matched
      comparison condition incorporating health education and scheduled, reduced
      smoking. There was a nonsignificant trend favoring CBT in achieving abstinence,
      but CBT did not enhance smokers' compensatory coping skills. Discussion focuses
      on the need to examine a wide range of possible mediating variables in future
      research on CBT for smoking cessation.

PMID- 16427746
TI  - Opening the floodgates: benign prostatic hyperplasia may represent another
      disease in the compendium of ailments caused by the global sympathetic bias that
      emerges with aging.
AB  - We have previously posited that the global sympathetic bias that emerges with
      aging may constitute the common etiologic thread that links a myriad of ailments
      associated with aging. Recent data suggests that benign prostatic hyperplasia
      (BPH) and associated lower urinary tract symptoms (LUTS) may also be caused by
      sympathetic bias as an independent etiology from androgen dysfunction. The
      association of BPH with heart disease, independent of other variables, supports
      the view that both entities represent downstream manifestations of global
      sympathetic bias. The risk for development of BPH increases with caffeine intake
      and decreases with alcohol consumption, factors which wield opposing effects on
      autonomic balance. Heavy smoking, which induces chronic sympathetic bias, also
      increases the risk of BPH, a link also previously attributed to hormonal
      alterations. Sympathetic dysfunction appears to have a mitogenic effect on the
      prostate. The high prevalence of prostate cancer, a condition detected in the
      autopsy of many elderly men, may arise from this activity combined with a Th2
      shift induced by sympathetic bias, leading to decreased cancer surveillance by
      the immune system. Exercise may improve BPH by restoring autonomic balance and
      normalizing the sympathovagal ratio. The benefits of alpha-adrenergic blockers on
      BPH, generally felt to achieve symptomatic relief afforded by bladder wall and
      sphincter remodeling, may independently exert a direct effect on prostate growth
      and enlargement. Sympathetic bias may play a role in adaptive enlargement of
      other organs such as the salivary glands, heart, liver, spleen, and skeletal
      muscles in response to stress. We envision novel pharmacologic and device-based
      neuromodulation therapies for BPH and related urologic dysfunctions based on
      these principles.

PMID- 16427747
TI  - Genome-wide scan reveals that genetic variation for transcriptional plasticity in
      yeast is biased towards multi-copy and dispensable genes.
AB  - One of the most important aspects of the evolution of development and physiology
      is the interplay between gene expression and the environment, by which traits
      become altered in response to environmental triggers. This feature is known as
      phenotypic plasticity. When different genotypes show different levels of
      plasticity for a trait, then they show genotype-by-environment interaction, or
      GEI. It is now clear that gene expression plays an important role in organismic
      level phenotypic plasticity, but we know very little about whether gene
      expression itself is subject to genetic variation for phenotypic plasticity
      (GEI). Given that gene regulation is likely to have evolved to respond to
      environmental changes, it is of central importance to understand how
      environmental and genetic variation interact to produce variation in gene
      expression. Here we investigate genetic variation for phenotypic plasticity in
      the yeast transcriptome for the whole genome. Six strains of Saccharomyces
      cerevisiae were grown in four different environments representing a continuum of
      rich and poor natural conditions. Using DNA-microarray data and an ANOVA analysis
      with a stringent criterion of significance, we found significant genetic
      variation for transcriptional plasticity (GEI) among strains for approximately 5%
      of the genes in the genome. There are about twice as many genes that show genetic
      variation for phenotypic plasticity as show genetic variation in transcription
      level independent of the environment. We also found that genes with genetic
      variation for plasticity were less likely to be essential and were significantly
      biased towards genes that have paralogs.

PMID- 16427748
TI  - Isolated endometrial polypoid sarcoidosis in a post-menopausal patient: case
      report.
AB  - We report here the first case of isolated uterine endometrial sarcoidosis
      presenting as an asymptomatic polypoid lesion. A 52-year-old patient, who had her
      last menstrual period 2 years before, was submitted to an office hysteroscopy
      because of an ultrasonographic finding of endometrial thickening preceding
      hormonal therapy. A polypoid endometrial lesion removed by surgical hysteroscopy
      revealed chronic granulomatous endometritis. After excluding other granulomatous
      diseases, the diagnose of sarcoidosis was corroborated. The finding of polypoid
      endometrial sarcoidosis expands the differential diagnoses possibilities in case
      of endometrial polyps.

PMID- 16427749
TI  - Batch grinding kinetics of Ethenzamide particles by fluidized-bed jet-milling.
AB  - Ethenzamide solids as a representative active pharmaceutical ingredient (API)
      were batch-ground by means of a fluidized-bed jet-mill which is a relatively new
      equipment and promising for production in the pharmaceutical field. Thus, the
      characteristic grinding mechanism was investigated. As a result, the variation of
      the residual ratio with grinding time after milling was expressed simply by a
      mathematical model using only the first Kapur function, and it was consistent
      with experimental data satisfactorily. As the shape of the function was much
      different from that of inorganic compound and peculiar to API, a cubic function
      with respect to particle diameter was defined newly and well fitted to the
      experimental data. The function was also found to be affected by the operating
      parameters as the grinding gas pressure, the charge weight of raw material and
      the linear velocity at the grinding nozzle. According to the assessments of the
      breakage and the selection functions derived from the first Kapur function, it
      was found that the grinding mechanism of Ethenzamide particles was related with
      particle attrition mainly.

PMID- 16427750
TI  - Nuclear and mitochondrial DNA quantification of various forensic materials.
AB  - Due to the different types and quality of forensic evidence materials, their DNA
      content can vary substantially, and particularly low quantities can impact the
      results in an identification analysis. In this study, the quantity of
      mitochondrial and nuclear DNA was determined in a variety of materials using a
      previously described real-time PCR method. DNA quantification in the roots and
      distal sections of plucked and shed head hairs revealed large variations in DNA
      content particularly between the root and the shaft of plucked hairs. Also large
      intra- and inter-individual variations were found among hairs. In addition, DNA
      content was estimated in samples collected from fingerprints and accessories. The
      quantification of DNA on various items also displayed large variations, with some
      materials containing large amounts of nuclear DNA while no detectable nuclear DNA
      and only limited amounts of mitochondrial DNA were seen in others. Using this
      sensitive real-time PCR quantification assay, a better understanding was obtained
      regarding DNA content and variation in commonly analysed forensic evidence
      materials and this may guide the forensic scientist as to the best molecular
      biology approach for analysing various forensic evidence materials.

PMID- 16427751
TI  - Ethanol production by Candida albicans in postmortem human blood samples: effects
      of blood glucose level and dilution.
AB  - We present two cases in which the ethanol concentration in blood samples taken
      after death continued to increase in the absence of any remarkable increase in n
      propanol concentration. Species of bacteria and yeasts, including Candida
      albicans were isolated from these samples. We then examined whether C. albicans,
      the most common yeast in the general environment, was able to produce ethanol in
      human blood stored at room temperature. Ethanol production increased as the
      glucose concentration increased, indicating that C. albicans produced ethanol
      from the glucose. Our results also suggested that C. albicans produced ethanol
      more easily in blood diluted by intravenous infusions that included glucose than
      in undiluted blood. These findings are useful for the evaluation of postmortem
      ethanol production in subjects whose blood has been diluted by infusions with
      glucose. Furthermore, there was no quantitative relationship between the amount
      of n-propanol detected and the amount of ethanol production: n-propanol appears
      to be an unreliable index of putrefaction and postmortem ethanol production by C.
      albicans. It is possible for the blood ethanol level to be high and n-propanol
      not to be detected, even if the subject has not been drinking alcohol. We
      reconfirmed the necessity of immediately adding sodium fluoride to samples for
      ethanol analysis to prevent postmortem ethanol production.

PMID- 16427752
TI  - Post-traumatic pseudomeningocele presenting as a cyst of external auditory canal:
      report of a case.
AB  - Pseudomeningoceles are formed by extravasation of cerebrospinal fluid through a
      dural defect into soft tissue. They mostly form as a result of surgical trauma to
      the dural covering of the lumbar or cervical spine surgery, especially during
      laminectomy. Howerver, post-traumatic pseudomeningocele rarely occurs in the head
      and neck. A 32-year-old female presented with a 10-year history of right ear
      fullness following head trauma. A soft, non-pulsatile and cystic mass was noted
      in the right external auditory canal. The MRI scan demonstrated the connection
      between subarachnoid space and cyst of the right external auditory canal. The
      right ear was explored and mastoid antrum was partially filled with a cyst
      connected to the dural defect. The extradural portion of the mass was removed,
      the dural defect was repaired with a temporalis fascia-cartilage graft. Clinical
      manifestations, diagnosis and surgical approaches for post-traumatic
      pseudomeningocele arising in the head and neck region are briefly discussed.

PMID- 16427753
TI  - Sweat duct carcinoma of lip with multiple cervical lymph nodes metastasis.
AB  - Sclerosing sweat duct carcinoma (SSDC) is a rare cutaneous neoplasm. A 28-year
      old man presented with 2-3 years history of a tetter on his upper lip, and a 3 cm
      x 4 cm lymph node was palpable in the left submandibular area. MRI showed a mass
      in the upper lip extending into the buccal mucosa and orbicular muscle, and
      multiple cervical lymph nodes metastasis on both sides was suspected. A biopsy
      was performed to have revealed syringomatous carcinoma. The patient underwent
      operation of extended removal of the upper lip along with right upper neck
      dissection and left radical neck dissection. 8 cm x 6 cm sized free forearm flap
      was used for the reconstruction of the lip. Postoperative course of the patient
      was uneventful and he has no signs of recurrence so far. Pertinent literatures on
      this rare tumor are reviewed.

PMID- 16427754
TI  - Otologic manifestations of relapsing polychondritis. Review of literature and
      report of nine cases.
AB  - OBJECTIVE: Relapsing polychondritis (RP) is an episodic disease most likely of
      autoimmune etiology, characterized by recurrent inflammation of cartilaginous
      structures. METHODS: Retrospective case study at two tertiary referral centers
      with presentation of nine patients with otologic involvement of RP, review of the
      spectrum of otologic disorders seen, and treatment. RESULTS: The clinical course
      of otologic manifestations of RP was highly variable and ranged from mild to
      moderate. In 6/9 patients there was an association with other autoimmune
      disorders. In addition to recurrent auricular chondritis, which was present in
      8/9 patients, our patients had otitis externa, chronic myringitis, Eustachian
      tube dysfunction, conductive hearing loss, sensorineural hearing loss, and
      tinnitus. All patients had their diagnosis of RP made on the basis of their
      otologic involvement and the response to systemic corticosteroids. CONCLUSION:
      The diagnosis of RP is primarily clinical, but laboratory studies and biopsy may
      contribute as well. Once the diagnosis is suspected, the otolaryngologist should
      consider consultation with a rheumatologist to assist in the management of
      additional systemic manifestations.

PMID- 16427755
TI  - Synchrotron microradiography study on acute lung injury of mouse caused by
      PM(2.5) aerosols.
AB  - In order to investigate FeSO(4), ZnSO(4) (the two of main metal compositions of
      Shanghai PM(2.5) (particle matter with those aerodynamical diameter <2.5 microm))
      effects on acute lung injury, six solutions contained PM(2.5) aerosol particles,
      FeSO(4), ZnSO(4) and their mixtures were instilled intratracheally into mouse
      lungs for experiment. By 2 days after instillation, the live mice were checked in
      vivo by synchrotron refractive index microradiography. In addition after
      extracted and examined by dissection, the right lobes of lung were fixed by
      formalin, then imaged by synchrotron microradiography again. Corresponding parts
      of those lung tissues were embedded in paraffin for histopathologic study. The
      synchrotron X-ray microradiographs of live mouse lung showed different lung
      texture changes after instilled with different toxic solutions. Hemorrhage points
      in lung were observed more from those mice instilled by FeSO(4) contained toxin
      solutions groups. Bronchial epithelial hyperplasia can be observed in ZnSO(4)
      contained solution-instilled groups from histopathologic analysis. It was found
      that the acute lung injury of mice caused by solution of PM(2.5)+FeSO(4)+ZnSO(4)
      was more serious than other toxin solutions. Results suggested that FeSO(4)
      mainly induced hemorrhage and ZnSO(4) mainly induced inflammation and bronchiolar
      epithelial hyperplasia in the early toxicological effects of PM(2.5).

PMID- 16427756
TI  - Liver CT image processing: a short introduction of the technical elements.
AB  - In this paper, we describe the technical aspects of image analysis for liver
      diagnosis and treatment, including the state-of-the-art of liver image analysis
      and its applications. After discussion on modalities for liver image analysis,
      various technical elements for liver image analysis such as registration,
      segmentation, modeling, and computer-assisted detection are covered with examples
      performed with clinical data sets. Perspective in the imaging technologies is
      also reviewed and discussed.

PMID- 16427757
TI  - Sedimenticola selenatireducens, gen. nov., sp. nov., an anaerobic selenate
      respiring bacterium isolated from estuarine sediment.
AB  - The respiration of selenate, as a terminal electron acceptor has been known for
      over a decade, but the microorganisms involved in this respiration are largely
      unknown. Here we characterize a novel selenate-respiring bacterium, strain
      AK4OH1, isolated from an estuarine sediment enrichment culture. Strain AK4OH1 has
      the unique capability to oxidize aromatic acids, such as benzoate, 4
      hydroxybenzoate and 3-hydroxybenzoate, coupled to selenate respiration. This
      novel respiratory coupling has not been described before. Reduction of selenate
      is followed by stoichiometric accumulation of selenite. The strain grows in agar
      shake tubes forming bright red colonies due to precipitation of elemental
      selenium. Strain AK4OH1 is a strictly anaerobic bacterium, which can also respire
      nitrate and nitrite via denitrification. Analysis of the 16S rRNA gene sequence
      shows that this strain clusters with another selenate-reducing bacterium and a
      (per) chlorate reducing bacterium, within the Gammaproteobacteria, along with
      symbionts of bivalves and tubeworms. Based on its unique physiological
      capabilities and its 16S rRNA gene sequence phylogeny, we classify this strain
      AK4OH1 as a new genus and species with the proposed name Sedimenticola
      selenatireducens.

PMID- 16427758
TI  - Caffeic acid phenethyl ester (CAPE) attenuates cerebral vasospasm after
      experimental subarachnoidal haemorrhage by increasing brain nitric oxide levels.
AB  - BACKGROUND: Cerebral vasospasm, a medical complication of aneurysmal subarachnoid
      hemorrhage (SAH), is associated with high morbidity and mortality rates, even
      after the aneurysm has been secured surgically or endovascularly. Evidence
      accumulated during the last decade suggest that scavenging a vasodilator, nitric
      oxide (NO), by superoxide anions (O(2)(-)), and activating a strong
      vasoconstructor, protein kinase C (PKC), are the two most important mechanisms in
      the pathogenesis of vasospasm. Our aim in this study was to determine whether
      caffeic acid phenethyl ester (CAPE), a non-toxic oxygen free radical scavenger,
      prevents vasospasm in an experimental rat model of SAH. METHODS: Twenty eight
      rats (225-250 g) were divided into four groups equally: group 1, control group;
      group 2, SAH group; group 3, SAH plus placebo group; and group 4, SAH plus CAPE
      group. We used double haemorrhage method for SAH groups. Starting 6h after SAH,
      10 micromol/kg CAPE or an equal volume of 0.9% saline were administered by
      intraperitoneal injection twice daily for 5 days to SAH plus CAPE and SAH plus
      placebo groups, respectively. CAPE or 0.9% saline injections were continued up to
      5th day after SAH. Rats were sacrificed on the 5th day. Brain sections at the
      level of the pons were examined by light microscopy. Measurements were made for
      the cross-sectional areas of the lumen and the vessel wall (intimae plus media)
      of basilar artery by a micrometer. The levels of malondialdehyde (MDA), reduced
      glutathione (GSH), and nitric oxide (NO) were measured in rat brain tissue.
      RESULTS: Administration of CAPE significantly attenuated the vasoconstriction of
      the basilar artery. There were marked narrowing in the lumens of and thickening
      in the walls of basilar arteries in the SAH, and the SAH plus placebo compared
      with CAPE group (p < 0.001). We also observed that CAPE administration
      significantly decreased the tissue level of MDA, while significantly increased
      the tissue levels of GSH, NO in the SAH plus CAPE group compared to only SAH
      group, p < 0.05. CONCLUSIONS: Our results indicate that CAPE is effective in
      attenuating delayed cerebral vasoconstriction following experimental SAH. Our
      findings also suggest that the elevation of lipid peroxidation and reduction of
      NO bioavailability, resulting from the generation and the interaction of free
      radicals, have a significant role in the pathogenesis of vasospasm after SAH.

PMID- 16427759
TI  - The Dutch cancer information helpline: more critical patients after 10 years.
AB  - OBJECTIVE: This study was conducted to assess the impact and evaluation of the
      Dutch national cancer information helpline and to assess differences in
      evaluation and impact with a comparable study conducted in 1994. METHODS: A cross
      sectional survey was conducted among all callers from the target groups patients,
      friends/relatives and the general public who contacted the information helpline
      from December 2003 until March 2004 (response 59%; N=665). RESULTS: All
      characteristics of the helpline (provided information, educator's communication
      skills, and telephone aspects) were evaluated positively by a large majority of
      the respondents. All groups evaluated the impact of the helpline on overall
      satisfaction, anxiety, and meeting expectations positively. However, the three
      target groups showed different predictors for the outcome measures. CONCLUSION:
      It can be concluded that 10 years after the first study, callers are still very
      positive in their evaluation. However, the different characteristics of the
      helpline are nowadays slightly more negatively judged, particularly by patients.
      The installation of the voice response system (VRS) as well as the fact that
      people have more easily access to information about their disease might account
      for these differences in evaluation. PRACTICE IMPLICATIONS: To maintain the
      positive evaluations helpline educators as well as the VRS need to attune more to
      the different needs and problems of the target groups and provide tailored
      information.

PMID- 16427760
TI  - Cultural differences in medical communication: a review of the literature.
AB  - OBJECTIVE: Culture and ethnicity have often been cited as barriers in
      establishing an effective and satisfying doctor-patient relationship. The aim of
      this paper is to gain more insight in intercultural medical communication
      difficulties by reviewing observational studies on intercultural doctor-patient
      communication. In addition, a research model for studying this topic in future
      research is proposed. METHODS: A literature review using online databases
      (Pubmed, Psychlit) was performed. RESULTS: Findings reveal major differences in
      doctor-patient communication as a consequence of patients' ethnic backgrounds.
      Doctors behave less affectively when interacting with ethnic minority patients
      compared to White patients. Ethnic minority patients themselves are also less
      verbally expressive; they seem to be less assertive and affective during the
      medical encounter than White patients. CONCLUSION: Most reviewed studies did not
      relate communication behaviour to possible antecedent culture-related variables,
      nor did they assess the effect of cultural variations in doctor-patient
      communication on outcomes, leaving us in the dark about reasons for and
      consequences of differences in intercultural medical communication. Five key
      predictors of culture-related communication problems are identified in the
      literature: (1) cultural differences in explanatory models of health and illness;
      (2) differences in cultural values; (3) cultural differences in patients'
      preferences for doctor-patient relationships; (4) racism/perceptual biases; (5)
      linguistic barriers. It is concluded that by incorporating these variables into a
      research model future research on this topic can be enhanced, both from a
      theoretical and a methodological perspective. PRACTICE IMPLICATIONS: Using a
      cultural sensitive approach in medical communication is recommended.

PMID- 16427761
TI  - Views and approaches toward risks and benefits among doctors who become patients.
AB  - OBJECTIVE: To understand how views and approaches concerning risks and benefits
      may be affected by dynamic contexts and processes related to clinical roles and
      relationships. METHODS: We conducted two in-depth, semi-structured interviews
      with 50 doctors who became patients due to serious illnesses, concerning their
      experiences before and after diagnosis. RESULTS: As patients, these doctors
      gained critical new insights into the processes and contexts of communication
      about risks and benefits. Doctors and patients often varied in how they viewed
      and weighed risks and benefits (e.g., as "good' or "bad"). These data suggest a
      model in which patients undergo several dynamic processes: seeking statistics,
      accepting doctors' framing of statistics, being influenced by media hype, seeing
      statistics as relevant or not, over-valuing risks, weighing the importance of
      risks and benefits, interpreting statistics as good or bad, accepting or denying
      statistics and odds, and making treatment decisions. These processes are affected
      by external factors (e.g., doctors ordering tests, framing statistics, and often
      over- versus under-valuing risks), and internal factors (e.g., depression, denial
      of illness, optimism versus pessimism, magical thinking--that doctors are immune
      to disease--and rationalizations). CONCLUSIONS: Doctors and patients are engaged
      in complex, dynamic processes that shape patients' approaches toward risks and
      benefits. PRACTICE IMPLICATIONS: These data highlight the need for increased
      attention toward these issues in medical educational and care.

PMID- 16427762
TI  - Improving comprehension of informed consent.
AB  - OBJECTIVE: To explore the way the doctor-patient communication process may be
      improved by adopting the patients' conversational style in the development of
      written materials for surgical patients. METHODS: Written information prepared by
      doctors, specialists in abdominal surgery, was tested for comprehension on
      patients undergoing cholecystectomy, using the standard Cloze test procedure. At
      the same time, the patients were asked to describe in their own words all they
      knew about their illness and the treatment. The collected 150 patient narratives
      were analyzed, and a typical narrative for each educational level was selected
      based on average SMOG score, word count and sentence length. The patient-worded
      information was then tested for comprehension on new patients, selected from
      primary health care, using the same Cloze procedure as with doctor-developed
      information. Patient profile of best lay communicators was defined using also
      sociodemographic characteristics, and reported information seeking and decision
      making preferences. RESULTS: Only 50% of patients completed Cloze test, of which
      over 40% showed poor comprehension. Analysis of transcribed narratives collected
      from 150 patients showed increasing complexity of style by educational level
      (average SMOG score 7, 8, and 9; sentence length 11, 13, and 15 words; for low,
      medium, and high educational level, respectively). Cloze tests based on typical
      narratives, and tested on primary care patients, indicated to the style best
      understood by all. Dominant characteristics of patients producing a narrative of
      similar style to the best-understood narrative were observed: medium educational
      level, women over 60, urban workers, interviewed after surgery, informed by
      specialist at ultrasound, knowledge about illness from 1 to 10 years, learned
      most about illness from lay people, those who wanted more information in both
      oral and written form, and preferred active role in decision making. CONCLUSION:
      Analysis of patient profiles with typical narratives that were best understood by
      other patients shows where to look for lay experts in doctor-patient
      communication. PRACTICE IMPLICATIONS: Obtained findings indicate to the
      importance of patient participation in developing informed consent information,
      and to the possible method for improving comprehension of educational patient
      materials in general.

PMID- 16427763
TI  - Attachment in families with Huntington's disease. A paradigm in clinical
      genetics.
AB  - OBJECTIVE: Based on the premise that attachment experiences lead to a working
      model for social relationships throughout life, this study investigates if there
      is a difference between adult attachment representations in individuals who were
      brought up by a parent with Huntington's disease (HD), compared to a non-clinical
      population. Specific events in the parents' disease process, especially those
      leading to trauma and loss will receive attention. METHODS: Using the Adult
      Attachment Interview, adult attachment representations were investigated in 32
      unaffected adults at 50% risk for HD who were raised by an affected parent.
      RESULTS: We found a lower percentage of secure attachment representations, a
      higher percentage of preoccupied representations, and a higher percentage of
      unresolved/disorganized representations in our sample, compared to a non-clinical
      population. A relatively late start of the parent's HD career was associated with
      a secure adult attachment representation. Death of the HD parent before the
      child's 18th birthday was associated with an unresolved/disorganized adult
      attachment representation. CONCLUSION: Growing up in a family where one of the
      parents has Huntington's disease appears to affect the offspring's adult
      attachment representation. PRACTICE IMPLICATIONS: This study can be of relevance
      for genetic counselling, as well as for counselling and intervention in
      childrearing matters.

PMID- 16427764
TI  - Determinants of poor adherence in hypertensive patients: development and
      validation of the "Maastricht Utrecht Adherence in Hypertension (MUAH)
      questionnaire".
AB  - OBJECTIVES: (1) To help identify patients with poor adherence and (2) to identify
      potential reasons that impede or facilitate adherence. METHODS: Seventeen
      patients who used antihypertensive drugs participated in semi-standardized
      interviews. Interviews were recorded and reviewed by two investigators. Forty
      four items were selected. An exploratory factor analysis was performed.
      Convergent validity was assessed by evaluating the association between sum scores
      on the identified subscales and three other adherence measures: (1) the Brief
      Medication Questionnaire (BMQ), (2) pharmacy refill records and (3) electronic
      monitoring. Regression analysis was used to evaluate the magnitude of
      associations. RESULTS: Two hundred and fifty-five (90%) patients completed the
      questionnaire. Factor analysis resulted in a four-factor solution, explaining 30%
      of cumulative variance among respondents. The factors (scales) were labeled:
      positive attitude towards health care and medication (I), lack of discipline
      (II), aversion towards medication (III) and active coping with health problems
      (IV). Chronbach's alpha coefficient was 0.75, 0.80, 0.63 and 0.76 for scales I,
      II, III and IV, respectively. Convergent validity was partly supported by
      statistically significant associations that were found between sum scores of
      subscales 1 and II and the BMQ and electronic monitoring, respectively.
      CONCLUSION: The MUAH-questionnaire has excellent psychometric properties and may
      be useful to identify factors that impede or facilitate adherence. However, it is
      not clear to what extent the questionnaire measures actual adherence. PRACTICE
      IMPLICATIONS: Validation of the MUAH-questionnaire in other studies is needed.

PMID- 16427765
TI  - Expression of firefly luciferase in Candida albicans and its use in the selection
      of stable transformants.
AB  - The infectious yeast Candida albicans is a model organism for understanding the
      mechanisms of fungal pathogenicity. We describe the functional expression of the
      firefly luciferase gene, a reporter commonly used to tag genes in many other
      cellular systems. Due to a non-standard codon usage by this yeast, the CUG codons
      were first mutated to UUG to allow functional expression. When integrated into
      the chromosome of C. albicans with a strong constitutive promoter, cells
      bioluminesce when provided with luciferin substrate in their media. When fused to
      the inducible promoter from the HWP1 gene, expression and bioluminescence was
      only detected in cultures conditioning hyphal growth. We further used the
      luciferase gene as a selection to isolate transformed cell lines from clinical
      isolates of C. albicans, using a high-density screening strategy that purifies
      transformed colonies by virtue of light emission. This strategy requires no drug
      or auxotrophic selectable marker, and we were thus able to generate stable
      transformants of clinical isolates that are identical to the parental strain in
      all aspects tested, other than their bioluminescence. The firefly luciferase gene
      can, therefore, be used as a sensitive reporter to analyze gene function both in
      laboratory and clinical isolates of this medically important yeast.

PMID- 16427767
TI  - The acoustic characteristics of professional opera singers performing in chorus
      versus solo mode.
AB  - In this study, members of a professional opera chorus were recorded using close
      microphones, while singing in both choral and solo modes. The analysis included
      computation of long-term average spectra (LTAS) for the two song sections
      performed and calculation of singing power ratio (SPR) and energy ratio (ER),
      which provide an indication of the relative energy in the singer's formant
      region. Vibrato rate and extent were determined from two matched vowels, and SPR
      and ER were calculated for these vowels. Subjects sung with equal or more power
      in the singer's formant region in choral versus solo mode in the context of the
      piece as a whole and in individual vowels. There was no difference in vibrato
      rate and extent between the two modes. Singing in choral mode, therefore,
      required the ability to use a similar vocal timbre to that required for solo
      opera singing.

PMID- 16427766
TI  - Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the
      AVPV.
AB  - There is growing concern that naturally occurring and chemically manufactured
      endocrine-active compounds (EACs) may disrupt hormone-dependent events during
      central nervous system development. We examined whether postnatal exposure to the
      phytoestrogen genistein (GEN) or the plastics component bisphenol-A (BIS)
      affected sexual differentiation of the anteroventral periventricular nucleus of
      the hypothalamus (AVPV) in rats. The AVPV is sexually differentiated in rodents.
      The female AVPV is larger than the male AVPV and contains a higher number of
      cells expressing tyrosine hydroxylase (TH). Sexual differentiation of the AVPV
      results from exposure of the male nervous system to estrogen aromatized from
      testicular testosterone secreted in the first few days after birth. Thus, we
      hypothesized that exposure to EACs during this critical period could alter the
      sexually dimorphic expression of TH and the overall expression of estrogen
      receptor alpha (ERalpha) in the AVPV. Animals were given 4 subcutaneous
      injections of sesame oil (control), 50 microg 17beta-estradiol (E2), 250 microg
      GEN, or 250 microg BIS at 12-h intervals over postnatal days (PND) 1 and 2 and
      sacrificed on PND 19. E2 treatment masculinized TH immunoreactivity (TH-ir) in
      the female AVPV while exposure to GEN or BIS demasculinized TH-ir in the male
      AVPV. In addition, we identified a population of neurons co-expressing TH and
      ERalpha located primarily in the medial region of the AVPV. Normally, females
      have nearly three times as many double-labeled cells as males, but their numbers
      were defeminized by E2, GEN or BIS treatment. These results suggest that acute
      exposure to EACs during a critical developmental period alters AVPV development.

PMID- 16427768
TI  - Voice care knowledge among clinicians and people with healthy voices or
      dysphonia.
AB  - An important clinical component in the prevention and treatment of voice
      disorders is voice care and hygiene. Research in voice care knowledge has mainly
      focussed on specific groups of professional voice users with limited reporting on
      the tool and evidence base used. In this study, a questionnaire to measure voice
      care knowledge was developed based on "best evidence." The questionnaire was
      validated by measuring specialist voice clinicians' agreement. Preliminary data
      are then presented using the voice care knowledge questionnaire with 17 subjects
      with nonorganic dysphonia and 17 with healthy voices. There was high (89%)
      agreement among the clinicians. There was a highly significant difference between
      the dysphonic and the healthy group scores (P = 0.00005). Furthermore, the
      dysphonic subjects (63% agreement) presented with less voice care knowledge than
      the subjects with healthy voices (72% agreement). The questionnaire provides a
      useful and valid tool to investigate voice care knowledge. The findings have
      implications for clinical intervention, voice therapy, and health prevention.

PMID- 16427769
TI  - Periorbital and midfacial rejuvenation via blepharoplasty and sub-periosteal
      midface rhytidectomy.
AB  - The stigmata of midfacial ageing are the malar descent, lateral orbital festoon
      formation, tear-through deformity, deep melojugal sulcus, buccal fat pad and sub
      orbicularis oculi fat (SOOF) prolapse, deep nasolabial folds and cutaneous and
      muscular descent. The signs of periorbital ageing include dermatochalasis, skin
      hooding of the upper eyelids, lacrimal gland prolapse, adipose prolapse, and
      lateral canthal descent and orbital septum diastasis. All of these deformities
      can be addressed through upper and lower blepharoplasties with arcus marginalis
      release, lateral canthopexy, sub-periosteal midface rhytidectomy with temporal
      suspension of the malar mound and SOOF repositioning. The same technique can be
      utilized for the restoration of facial symmetry after Bell's palsy. In the
      following report the technique and the authors' experience in the rejuvenation of
      the periorbital and midface region are presented. There were a total of 20
      patients in this series. Sixteen were female and 4 were male. All the patients
      were followed-up on a monthly basis after surgery for the first 6 months. They
      were then seen at 1 year post-surgery. All of the patients were evaluated by the
      senior author. In the beginning of the study there was 1 Asian female patient
      with mild postoperative ectropion, which resolved and did not require operative
      intervention. The patients experienced prolonged postoperative oedema. The
      patients were satisfied with their postoperative outcomes. In all patients, the
      goals of periorbital and midfacial rejuvenation were achieved with the above
      technique. Simultaneous periorbital and midfacial rejuvenation can be achieved
      via upper and lower blepharoplasties, lateral canthopexies and sub-periosteal
      midface rhytidectomy.

PMID- 16427770
TI  - TrwB: an F(1)-ATPase-like molecular motor involved in DNA transport during
      bacterial conjugation.
AB  - The mechanism by which TrwB acts as a DNA transporter in bacterial conjugation is
      analyzed. Based on a parallelism between TrwB and F(1)-ATPase, TrwB would use the
      energy derived from ATP hydrolysis to pump DNA through its central channel, in a
      manner similar to that used by F(1)-ATPase to produce a rotary movement of the
      central gamma-subunit.

PMID- 16427771
TI  - Bap: a family of surface proteins involved in biofilm formation.
AB  - A group of surface proteins sharing several structural and functional features is
      emerging as an important element in the biofilm formation process of diverse
      bacterial species. The first member of this group of proteins was identified in a
      Staphylococcus aureus mastitis isolate and was named Bap (biofilm-associated
      protein). As common structural features, Bap-related proteins: (i) are present on
      the bacterial surface; (ii) show a high molecular weight; (iii) contain a core
      domain of tandem repeats; (iv) confer upon bacteria the capacity to form a
      biofilm; (v) play a relevant role in bacterial infectious processes; and (vi) can
      occasionally be contained in mobile elements. This review summarizes recent
      studies that have identified and assigned roles to Bap-related proteins in
      biofilm biology and virulence.

PMID- 16427772
TI  - The role of the Rcs phosphorelay in Enterobacteriaceae.
AB  - The Rcs phosphorelay is composed of the sensor kinase, RcsC, the HPt-domain
      protein RcsD and the response regulator, RcsB. In this review we discuss the role
      of the Rcs phosphorelay in the Enterobacteriaceae, highlighting the observation
      that the Rcs phosphorelay appears to play a key role in the temporal regulation
      of biofilm formation and pathogenicity.

PMID- 16427773
TI  - A study of the nuclear trafficking of the splicing factor protein PRPF31 linked
      to autosomal dominant retinitis pigmentosa (ADRP).
AB  - In this study the mechanism of nuclear importation of the splicing factor PRPF31
      is examined and the impact of two disease-linked mutations, A194E and A216P,
      assessed. Using pull-down assays with GST-tagged importin proteins, we
      demonstrate that His-tagged PRPF31 interacts with importin beta1 for
      translocation to the nucleus, with no requirement for importin alpha1. The A194E
      and A216P mutations have no affect on this interaction. Fluorescence recovery
      after photobleaching (FRAP) was used to estimate the rate of movement of EGFP
      tagged PRPF31 into the nuclei of live cells. The kinetics indicated a two
      component recovery process; a fast component with tau approximately 6 s and a
      slow component with tau approximately 80 s. The mutations affected neither
      component. We conclude that the two mutations have no negative effect on
      interaction with the nuclear importation machinery. Reduced mutant protein
      solubility resulting in an insufficiency of splicing activity in cells with a
      very high metabolic demand remains the most likely explanation for the disease
      pathology in ADRP patients.

PMID- 16427774
TI  - Relationships between analytical methods utilized as tools in the evaluation of
      landfill waste stability.
AB  - In this study, the refuse from 12 landfills of various ages ranging from fresh
      refuse to material 11 years old was collected, and changes in the bio-stability
      parameters were determined. The parameters measured included cellulose, lignin,
      biochemical methane potential (BMP) and volatile solids, along with plastics.
      These parameters, along with the cellulose to lignin ratio were compared to
      determine which were most indicative of the bio-stability of the refuse. Lignin
      and volatile solids measurements were affected by plastics in refuse samples.
      Plastics increased both lignin and volatile solids measurements by approximately
      10%. Cellulose and volatile solids measurements correlated well with age, each
      other, and with BMP measurements and were therefore considered the best
      parameters to determine stability. Data for the Riverbend landfill, a landfill
      with a moisture content of 48%, which is similar to that of bioreactor landfills,
      showed that degradation was nearly complete after 5 years as indicated by low
      values for cellulose and BMP.

PMID- 16427775
TI  - A disposable electrochemical immunosensor for flow injection immunoassay of
      carcinoembryonic antigen.
AB  - A new simple immunoassay method for carcinoembryonic antigen (CEA) detection
      using a disposable immunosensor coupled with a flow injection system was
      developed. The immunosensor was prepared by coating CEA/colloid Au/chitosan
      membrane at a screen-printed carbon electrode (SPCE). Using a competitive
      immunoassay format, the immunosensor inserted in the flow system with an
      injection of sample and horseradish peroxidase (HRP)-labeled CEA antibody was
      used to trap the labeled antibody at room temperature for 35 min. The current
      response obtained from the labeled HRP to thionine-H(2)O(2) system decreased
      proportionally to the CEA concentration in the range of 0.50-25 ng/ml with a
      correlation coefficient of 0.9981 and a detection limit of 0.22 ng/ml (S/N=3).
      The immunoassay system could automatically control the incubation, washing and
      current measurement steps with good stability and acceptable accuracy. Thus, the
      proposed method proved its potential use in clinical immunoassay of CEA.

PMID- 16427776
TI  - NMR studies of protein interactions.
AB  - Interactions of proteins with other macromolecules or small molecules play
      important roles in most biological processes. Often, such interactions are weak
      and transient, and the complexes do not easily crystallize. NMR spectroscopy has
      the unique ability to retrieve information about these interactions and is
      increasingly used. Recent methodological developments have helped characterize
      weak protein interactions, and have in particular been applied to the study of
      proteins that are mostly unfolded alone but form well-defined complexes upon
      interaction. In addition, NMR methods have been applied to the identification and
      characterization of small chemicals that inhibit protein function, a primary
      objective of rational drug design.

PMID- 16427777
TI  - Association between different alcoholic beverages and leukoplakia among non- to
      moderate-drinking adults: a matched case-control study.
AB  - While heavy drinking is a risk factor for oral leukoplakia, the effects of
      moderate drinking and of different alcoholic beverages are unclear and were
      investigated in this case-control study. 187 leukoplakia patients, aged 40-65
      years, who were not heavy drinkers and did not change their drinking/smoking
      habits over the last decade, were age/gender matched to 187 controls. The effect
      of regular, moderate, overall alcohol, beer, wine, spirit drinking, adjusted for
      the effects of heavy smoking and other important co-variables, were assessed
      using conditional logistic regression analysis. Overall alcohol (OR, 0.22), wine
      (OR, 0.20), spirits (OR, 2.93) were significantly associated to leukoplakia. A
      statistically significant interaction wine/heavy smoking was also found. Such
      different effects could be explained by the ethanol antagonising potential of
      other drink components, such as polyphenols, abundant in red wine and scarce in
      spirits. Among heavy smokers, the preventive effect of wine was more than
      multiplicative.

PMID- 16427778
TI  - Recent developments in the use of chemotherapy in brain tumours.
AB  - Several recent studies have further clarified the role of chemotherapy in newly
      diagnosed anaplastic glioma. For newly diagnosed glioblastoma, combined daily
      radiotherapy with daily temozolomide followed by six cycles of adjuvant
      temozolomide improves overall survival. This benefit is especially observed in
      patients with a methylated promotor of the MGMT gene which encodes an
      alkyltransferase; this observation however, needs confirmation. Although
      oligodendroglial tumours are sensitive to chemotherapy, classical adjuvant
      nitrosourea-based chemotherapy does not improve overall survival in newly
      diagnosed anaplastic oligodendroglioma, even in the subset of 1p/19q loss
      tumours. It may increase progression-free survival however, and further studies
      must show if combined modality treatment with daily chemotherapy during
      radiotherapy increases survival. Trials exploring the role of chemotherapy in low
      grade glioma are ongoing. No standard chemotherapy is currently available for
      highly anaplastic glioma failing first-line temozolomide-based therapy.

PMID- 16427779
TI  - Irinotecan as first-line chemotherapy in patients with advanced hepatocellular
      carcinoma: a multicenter phase II study with dose adjustment according to
      baseline serum bilirubin level.
AB  - This study assessed the clinical activity and safety of irinotecan (CPT-11) in
      patients with advanced hepatocellular carcinoma (HCC) using dose adjustment
      according to baseline serum bilirubin level. Patients with advanced HCC received
      CPT-11 at a dose of 350 mg/m(2) when total bilirubin level was 1.5 times upper
      limit of normal (ULN) (group A), or 200 mg/m(2) when total bilirubin level was
      between 1.51 and 3 ULN (group B). No objective response, one minor response and
      12 disease stabilizations were observed in the 29 patients (group A, 23; group B,
      6) enrolled. Median time to progression and overall survival were 3.1 months (95%
      confidence interval [CI]: 2.0-4.0) and 7.4 months (95% CI: 3.9-12.0),
      respectively. Grade 3-4 adverse events (mostly neutropenia [47%], anaemia [24%],
      and diarrhoea [17%]) were more frequent in group A (74%) than in group B (33%) (P
      = 0.086). This study found favourable toxicity profile using dosage adjustment to
      the baseline total bilirubin level in patients with bilirubin level comprised
      between 1.51 and 3 ULN. However, the antitumour activity of single agent CPT-11
      was not significant in advanced HCC.

PMID- 16427780
TI  - Is MSI-H of value in predicting the development of metachronous colorectal
      cancer?
AB  - Nearly 10% of patients with colorectal cancer (CRC) develop a metachronous cancer
      after curative resection of their primary malignancy, however identifying these
      patients is problematic. Although microsatellite instability (MSI) is associated
      with the development of multiple CRC, this is predominantly seen in those with
      hereditary non-polyposis colon cancer (HNPCC). This study has examined the value
      of MSI analysis in identifying patients at risk of developing metachronous cancer
      from the general population. MSI analysis was performed at the Bat25, Bat26,
      Bat40, D2S123, D5S346 and D17S250 loci using polymerase chain reaction and single
      stranded conformational polymorphism on DNA extracted from 62 specimens taken
      from 49 patients with metachronous CRC, and from 71 primary single CRCs. MSI
      status was classified into MSI-H, MSI-L and MSS. MSI-H was more prevalent in
      metachronous cancers, 34/62 compared to 8/71 single cancers (P < 0.0001). The
      incidence of MSI-H from proximal colon cancers in index metachronous group, 4/22
      was similar to single cancer group, 7/71 (P = 0.28), however MSI-H was more
      commonly identified in index metachronous cancers located distal to the splenic
      flexure 9/22 than single cancers 1/71 (P < 0.0001). Patients presenting with MSI
      H colorectal cancers distal to the splenic flexure are more likely to develop a
      metachronous cancer and will benefit from surveillance.

PMID- 16427781
TI  - Ultrasonic treatment of biological sludge: Floc disintegration, cell lysis and
      inactivation.
AB  - The aim of this work was to study the effect of ultra sound treatment on the
      solid content of sludge and biological activity, and the increase in the soluble
      chemical oxygen demand (SCOD), proteins and nucleic acids concentrations during
      sonication. The results showed that sonication effectively degraded and
      inactivated the sludge. The sludge disintegration and cell lysis occurred
      continuously while sludge inactivation mainly occurred in the second stage (10-30
      min) during sonication. The SCOD, supernatant proteins and nucleic acids
      concentrations, and sludge mass reduction and inactivation degrees increased with
      the sonication time and power density increases. Higher energy ultrasound was
      more efficient than lower energy ultrasound for the sludge treatment.

PMID- 16427782
TI  - Reliability of the Hammersmith functional motor scale for spinal muscular atrophy
      in a multicentric study.
AB  - The aim of this study was to validate the Hammersmith functional motor scale for
      children with spinal muscular atrophy in a large cohort of 90 non-ambulant
      children with spinal muscular atrophy type 2 or 3. All had a baseline assessment
      (T0) and were reassessed either at 3 months (T1) (n = 66) or at 6 months (T2) (n
      = 24). Inter-observer reliability, tested on 13 children among 3 examiners, was >
      95%. Of the 66 children examined after 3 months 4 had adverse effects in between
      assessments and were excluded from the analysis. Forty-two (68%) of the remaining
      62 reassessed had no variation in scores between T0 and T1 and 13 (21%) were
      within +/- 1 point. 9 (37.5%) of the 24 children reassessed after 6 months had no
      variation in scores between T0 and T2 and another 9 (37.5%) had variations within
      +/- 1 point. Our study confirms previous observations of the reliability of the
      scale and helps to establish a baseline for assessing changes of functional
      ability over 3 and 6 month intervals. This information can be valuable in view of
      therapeutic trials.

PMID- 16427783
TI  - Eosinophilic fasciitis in a child mimicking a myopathy.
AB  - A 14-year-old boy was suspected of having a myopathy with joint contractures. He
      presented with progressive painless joint contractures of his right wrist and
      fingers, and reduced muscle strength of his right arm, without obvious skin
      changes. Laboratory investigation showed a normal CK, hypergammaglobulinemia and
      eosinophilia. Ultrasonography revealed thickened fasciae in the forearm. A full
      thickness biopsy confirmed the diagnosis of eosinophilic fasciitis. The
      contractures diminished quickly with prednisolone and methotrexate. The
      ultrasound scans 2 years after diagnosis showed improvement, although some
      thickening of the fasciae was still present, indicating residual changes. In
      conclusion, eosinophilic fasciitis has to be regarded as a differential diagnosis
      of painless joint contractures in children. Ultrasonography can be helpful to
      suspect the diagnosis.

PMID- 16427784
TI  - Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713
      using [11C]methyl triflate.
AB  - Recently, the pyrazolopyrimidine, [11C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7
      dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a
      new promising marker for the study of peripheral benzodiazepine receptors with
      positron emission tomography. In the present study, DPA-713 has been labelled
      from the corresponding nor-analogue using [11C]methyl triflate (CH3OTf).
      Conditions for HPLC were also modified to include physiological saline (aq. 0.9%
      NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total
      time of radiosynthesis, including HPLC purification, was 18-20 min. This reported
      synthesis of [11C]DPA-713, using [11C]CH3OTf, resulted in an improved
      radiochemical yield (30-38%) compared to [11C]methyl iodide (CH3I) (9) with a
      simpler purification method. This ultimately enhances the potential of [11C]DPA
      713 for further pharmacological and clinical evaluation. These improvements make
      this radioligand more suitable for automated synthesis which is of benefit where
      multi-dose preparations and repeated syntheses of radioligand are required.

PMID- 16427785
TI  - Cardiotrophin-1 induces monocyte chemoattractant protein-1 synthesis in human
      umbilical vein endothelial cells.
AB  - In chronic heart failure (CHF) cardiotrophin-1 (CT-1) and monocyte
      chemoattractant protein-1 (MCP-1) plasma concentrations are elevated. CT-1 is a
      cytokine of the interleukin-6 (IL-6) superfamily. Most members of the IL-6 family
      are able to activate human umbilical vein endothelial cells (HUVEC) but so far
      there are no data which demonstrate that CT-1 can activate HUVEC. Because MCP-1
      as a marker of endothelial activation-is elevated in CHF we examined whether CT-1
      will induce MCP-1 production in HUVEC. MCP-1 mRNA levels were determined by real
      time PCR, RT-PCR and northern blot analysis and MCP-1 protein concentrations in
      the supernatant by ELISA. Signal transducer and activator of transcription 3
      (STAT3) and phosphorylated STAT3 (pSTAT3) were investigated by western blot
      analysis. Incubation of HUVEC with different CT-1 concentrations for various time
      periods induced time and concentration dependent MCP-1 mRNA. Maximal MCP-1 mRNA
      was reached after 6h. After 24h CT-1 caused a significant induction of MCP-1
      protein in the supernatant compared to control. CT-1 induced concentration
      dependent phosphorylation of STAT3 without any change in total-STAT3
      concentration. Piceatannol-a specific blocker of STAT3 phosphorylation-inhibited
      CT-1 induced MCP-1 induction completely. AG490-a blocker of the JAK2 pathway-was
      also able to inhibit CT-1 induced MCP-1 upregulation, indicating that the JAK2
      pathway is also necessary for MCP-1 induction. Parthenolide-a blocker of NFkappaB
      inhibited CT-1 induced MCP-1 expression, completely. Our data show that CT-1
      induces in a concentration and time dependent manner MCP-1 mRNA and protein in
      HUVEC. STAT3 phosphorylation, the activation of JAK2 and NF-kappaB are involved
      in this pathway. In CHF, CT-1 may be able to induce MCP-1 which might be
      responsible for progression of heart failure either by recruiting inflammatory
      cells within the myocardium or by a direct modulation of myocyte function.

PMID- 16427786
TI  - A comparison of liquid nitrogen and liquid helium as cryogens for electron
      cryotomography.
AB  - The principal resolution limitation in electron cryomicroscopy of frozen-hydrated
      biological samples is radiation damage. It has long been hoped that cooling such
      samples to just a few kelvins with liquid helium would slow this damage and allow
      statistically better-defined images to be recorded. A new "G2 Polara" microscope
      from FEI Company was used to image various biological samples cooled by either
      liquid nitrogen or liquid helium to approximately 82 or approximately 12 K,
      respectively, and the results were compared with particular interest in the doses
      (10-200 e-/A2) and resolutions (3-8 nm) typical for electron cryotomography.
      Simple dose series revealed a gradual loss of contrast at approximately 12K
      through the first several tens of e-/A2, after which small bubbles appeared.
      Single particle reconstructions from each image in a dose series showed no
      difference in the preservation of medium-resolution (3-5 nm) structural detail at
      the two temperatures. Tomographic reconstructions produced with total doses
      between 10 and 350 e-/A2 showed better results at approximately 82 K than
      approximately 12 K for every dose tested. Thus disappointingly, cooling with
      liquid helium is actually disadvantageous for cryotomography.

PMID- 16427788
TI  - Inhibition of MCF-7 breast cancer cell proliferation by MCF-10A breast epithelial
      cells in coculture.
AB  - A coculture system was developed to investigate the interactions between MCF-10A
      breast epithelial cells and MCF-7 breast cancer cells stably expressing the green
      fluorescent protein (MCF-7-GFP). Studies with this MCF-10A/MCF-7-GFP coculture
      system on microtiter plates and on reconstituted basement membrane (Matrigel),
      revealed paracrine inhibition of MCF-7-GFP cell proliferation. Epidermal growth
      factor, which in monocultures modestly enhanced MCF-7-GFP and markedly increased
      MCF-10A cell proliferation, greatly inhibited MCF-7-GFP cell proliferation in MCF
      10A/MCF-7-GFP cocultures. 17beta-Estradiol, which stimulated MCF-7-GFP but not
      MCF-10A cell proliferation in monoculture, inhibited MCF-7-GFP cell proliferation
      in MCF-10A/MCF-7-GFP cocultures, an effect that was blocked by the antiestrogen,
      ICI 182,780. On Matrigel, complex MCF-10A/MCF-7-GFP cellular interactions were
      observed in real time that resulted in the formation of acinus-like structures.
      These results indicate a role of normal epithelial cells in inhibiting tumor-cell
      proliferation and demonstrate the utility of this coculture system as a model of
      early paracrine control of breast cancer.

PMID- 16427787
TI  - Sleep-anticipating effects of melatonin in the human brain.
AB  - Melatonin, the hormone produced nocturnally by the pineal gland, is an endogenous
      regulator of the sleep-wake cycle. The effects of melatonin on brain activities
      and their relation to induction of sleepiness were studied in a randomized,
      double-blind, placebo controlled functional magnetic resonance imaging (fMRI)
      study. Melatonin, but not placebo, reduced task-related activity in the rostro
      medial aspect of the occipital cortex during a visual-search task and in the
      auditory cortex during a music task. These effects correlated with subjective
      measurements of fatigue. In addition, melatonin enhanced the activation in the
      left parahippocampus in an autobiographic memory task. Results demonstrate that
      melatonin modulates brain activity in a manner resembling actual sleep although
      subjects are fully awake. Furthermore, the fatigue inducing effect of melatonin
      on brain activity is essentially different from that of sleep deprivation thus
      revealing differences between fatigues related to the circadian sleep regulation
      as opposed to increased homeostatic sleep need. Our findings highlight the role
      of melatonin in priming sleep-associated brain activation patterns in
      anticipation of sleep.

PMID- 16427789
TI  - Expression of growth factors and growth factor receptor in non-healing and
      healing ischaemic ulceration.
AB  - OBJECTIVES: To characterise the histological and cytokinetic characteristics of
      purely ischaemic ulcers and the processes that underpin healing following
      successful revascularisation. DESIGN: Prospective observational study. MATERIALS
      AND METHODS: Biopsies were taken immediately pre- and 6 weeks following
      successful revascularisation of solely ischaemic ulceration. They were evaluated
      for morphological differences using H&E staining for the platelet derived growth
      factor receptor (PDGFR), epidermal growth factor receptor (EGFR), TGFbeta
      receptorIII (TGFbetaRIII), transforming growth factor beta 1 and 3 (TGFbeta1 and
      TGFbeta3) and von Willebrand factor (vWF) expression using immunohistochemistry.
      Localisation and quantification of these growth factors and receptors was
      assessed systematically by three independent investigators who were blinded to
      the timing of biopsy. RESULTS: Pre-operatively, small vessel vasculitis, necrosis
      and infection with a profuse neutrophil and macrophage infiltrate was observed in
      all samples. Post-operative biopsies revealed a proliferation of new capillaries
      in and around the ulcer edge and base. vWF staining confirmed an endothelial
      layer within these new vessels. Following successful revascularisation there was
      less infection and inflammation with minimal vasculitis. These newly formed
      capillaries had increased staining for TGFbeta3, PDGFR and TGFbetaRIII with
      staining for PDGFR also localised to dermal fibroblasts which were larger and
      more numerous. Accelerated epithelial cell proliferation was observed with
      detachment from the underlying dermis. CONCLUSIONS: Healing of purely ischaemic
      ulcers is characterised by vasculogenesis associated with increased presence of
      the proangiogenic cytokines PDGF and TGFbeta3. These findings show promise for
      the use of growth factor manipulation to aid healing in ischaemic ulcers.

PMID- 16427790
TI  - Genetic and genomic prospects for Xenopus tropicalis research.
AB  - Research using Xenopus laevis has made enormous contributions to our
      understanding of vertebrate development, control of the eukaryotic cell cycle and
      the cytoskeleton. One limitation, however, has been the lack of systematic
      genetic studies in Xenopus to complement molecular and cell biological
      investigations. Work with the closely related diploid frog Xenopus tropicalis is
      beginning to address this limitation. Here, we review the resources that will
      make genetic studies using X. tropicalis a reality.

PMID- 16427791
TI  - Age-related impact of neuropathic pain on animal behaviour.
AB  - The number of old and very old persons is increasing and there is evidence that
      aging coincides with chronic painful conditions. Pain induces behavioural
      disorders that have been so far poorly identified in old and even less in very
      old animals. The aim of this study was to: (1) compare the evolution of pain in
      senescent animals (37-39 months) to old (20-22 months) and young (4-6 months)
      Lou/cjall rats after a chronic constriction of the sciatic nerve; (2) evaluate
      pain during four weeks after surgery with an experimental and an observational
      approach to determine how the response to noxious stimuli correlates with
      recorded spontaneous behaviour. Results showed that senescent animals are less
      sensitive to neuropathic pain than old or young rats while senescent/old rats are
      more sensitive to acute pain. The correlation between observational and
      experimental pain scores stresses the reliability of non-invasive measures for
      pain evaluation in senescent populations. The dichotomy between neuropathic and
      acute pain perceptions with age needs to be further investigated and would help
      to better understand the reasons of this uneven pain perception and expression
      with age.

PMID- 16427792
TI  - Predicting and preventing post-herpetic neuralgia: are current risk factors
      useful in clinical practice?
AB  - Post-herpetic neuralgia (PHN) following acute herpes zoster remains a significant
      cause of neuropathic pain especially in the elderly. Early treatment of the
      zoster rash with antiviral agents, such as aciclovir remains one of the few
      measures proven to reduce the incidence and duration of PHN albeit only in a
      subset of patients. It is therefore crucial that the physician who first sees a
      case of zoster identifies those patients who are most likely to develop long-term
      pain and treats them accordingly. In particular, prodrugs such as famciclovir and
      valaciclvoir may be more beneficial in reducing PHN than the shorter acting
      aciclovir, but can be more expensive. Measures that could be used to predict
      patients likely to develop PHN would also facilitate the evaluation of early use
      of antiepileptic, anti-inflammatory and analgesic agents in the prevention of
      PHN. In a prospective study of 280 herpes zoster (HZ) cases seen by the general
      practitioner (GP) we evaluated the predictive value of five clinical factors
      identified in clinical trials as associated with a higher likelihood of PHN. A
      visual analogue score (VAS) over 5 and/or age over 50 correctly identified all
      subjects with PHN at 3 and 6 months, respectively. However, the specificity of
      this prediction was low because as many as 81% and 85% of those aged over 50
      recovered within 3 and 6 months, respectively. Better methods are needed to
      identify patients over 50 at most risk of PHN that enable GPs to better allocate
      their resources with respect to HZ treatment.

PMID- 16427793
TI  - High-field ESR on aligned membranes: a simple method to record spectra from
      different membrane orientations in the magnetic field.
AB  - A combination of isopotential spin-dry ultracentrifugation (ISDU) and microtome
      techniques was used to facilitate the collection of high field/high frequency
      (170 GHz) ESR spectra corresponding to different orientations of the membrane
      normal relative to the magnetic field. This technique is particularly valuable
      for aligned biological samples in vitro. At 170 GHz, conventional sample
      preparation techniques based solely on ISDU constrained the sample to be oriented
      so that the membrane normal was parallel to the applied magnetic field due to the
      geometry and the millimeter wave field distribution of the Fabry-Perot resonator
      used in these experiments. This orientational constraint limited the information
      that could be obtained from aligned membranes at high field. The combined
      ISDU/microtome technique overcame this limitation. Spectra from spin-labeled
      Gramicidin A and the spin label cholestane in aligned DPPC membranes provide a
      demonstration of the technique. We also discuss some virtues of high field/high
      frequency ESR on aligned membranes compared to X-band.

PMID- 16427794
TI  - Fast imaging with the MMME sequence.
AB  - The multiple-modulation-multiple-echo sequence, previously used for rapid
      measurement of diffusion, is extended to a method for single shot imaging.
      Removing the gradient switching requirement during the application of RF pulses
      by a constant frequency encoding gradient can shorten experiment time for
      ultrafast imaging. However, having the gradient on during the pulses gives rise
      to echo shape variations from off-resonance effects, which make the image
      reconstruction difficult. In this paper, we propose a simple method to deconvolve
      the echo shape variation from the true one-dimensional image. This method is
      extended to two-dimensional imaging by adding phase encoding gradients between
      echoes during the acquisition period to phase encode each echo separately. Slice
      selection is achieved by a frequency selective pulse at the beginning of the
      sequence. Imaging speed is mainly limited by the phase encoding gradients'
      switching times and echo overlap when echo spacing is very short. This technique
      can produce a single-shot image of sub-millimeter resolution in 5 ms.

PMID- 16427795
TI  - Radiation damping in microcoil NMR probes.
AB  - Radiation damping arises from the field induced in the receiver coil by large
      bulk magnetization and tends to selectively drive this magnetization back to
      equilibrium much faster than relaxation processes. The demand for increased
      sensitivity in mass-limited samples has led to the development of microcoil NMR
      probes that are capable of obtaining high quality NMR spectra with small sample
      volumes (nL-microL). Microcoil probes are optimized to increase sensitivity by
      increasing either the sample-to-coil ratio (filling factor) of the probe or
      quality factor of the detection coil. Though radiation damping effects have been
      studied in standard NMR probes, these effects have not been measured in the
      microcoil probes. Here a systematic evaluation of radiation damping effects in a
      microcoil NMR probe is presented and the results are compared with similar
      measurements in conventional large volume samples. These results show that
      radiation-damping effects in microcoil probe is much more pronounced than in 5 mm
      probes, and that it is critically important to optimize NMR experiments to
      minimize these effects. As microcoil probes provide better control of the bulk
      magnetization, with good RF and B0 inhomogeneity, in addition to negligible
      dipolar field effects due to nearly spherical sample volumes, these probes can be
      used exclusively to study the complex behavior of radiation damping.

PMID- 16427796
TI  - Phosphodiesterase (PDE) 7 in inflammatory cells from patients with asthma and
      COPD.
AB  - In inflammatory cells, the low K(m) cyclic adenosine monophosphate (cAMP)
      specific phosphodiesterase (PDE) 4 subtype is predominant in terms of expression
      and function, although more recently it has been suggested that PDE 7 may also
      play a role in regulating inflammatory cell activity. In the present study, PDE 4
      and PDE 7 subtype messenger ribonucleic acid (mRNA) transcripts in CD4 and CD8
      lymphocytes from healthy (n=10) and asthmatic (n=10) subjects and
      polymorphonuclear neutrophils (PMNs) and CD8 lymphocytes obtained from healthy
      (n=10) and chronic obstructive pulmonary disease (COPD) (n=7) subjects were
      identified and quantified. PDE 4A, PDE 4B, PDE 4D and PDE 7A mRNA were present in
      similar quantities in both CD4 and CD8 lymphocytes obtained from healthy and
      asthmatic subjects and in CD8 lymphocytes obtained from healthy and COPD
      subjects. Expression of PDE 4C and PDE 7B mRNA was also observed, although
      transcript levels were low and variable between individuals. In addition, the
      effects of selective PDE 7 inhibition on both phytohaemagluttinin (PHA)-induced
      human peripheral blood mixed mononuclear cell (HPBMNC) proliferation and fMLP
      induced neutrophil elastase (NE) release were studied. HPBMNC and human
      neutrophils, isolated from the venous blood of healthy volunteers (n=6) were
      treated with either a novel selective PDE 7 inhibitor PF 0332040 alone or in
      combination with rolipram. Proliferation of HPBMNC was stimulated by PHA
      (2microgml(-1)) and assessed by [(3)H]-thymidine incorporation, while fMLP
      induced (100nM) NE release was determined using a chromogenic substrate. Both
      rolipram (0.003-10microM) and PF 0332040 (0.003-10microM) significantly inhibited
      PHA-stimulated proliferation of HPBMNC ((**)P<0.01). Co-administration of
      rolipram (0.3-10microM) and PF 0332040 (0.003-10microM) significantly increased
      the degree of inhibition observed, compared to when either drug was administered
      alone ((**)P<0.01). PF 0332040 (0.003-10microM) had no inhibitory effect on NE
      release from human peripheral blood neutrophils stimulated with fMLP (100nM),
      while rolipram (0.003-10microM) significantly inhibited neutrophil degranulation
      ((**)P<0.01). These findings suggest no evidence of altered PDE 4 or PDE 7 mRNA
      transcript levels in inflammatory cells isolated from the peripheral venous blood
      of mild asymptomatic asthmatic subjects or stable COPD subjects, however,
      inhibition of PDE 7 may influence mononuclear cell function.

PMID- 16427797
TI  - CYP21A2 mutations in Portuguese patients with congenital adrenal hyperplasia:
      identification of two novel mutations and characterization of four different
      partial gene conversions.
AB  - More than 90% of congenital adrenal hyperplasia (CAH) cases are caused by 21
      hydroxylase deficiency. In this study, the CYP21 gene was genotyped in 56
      Portuguese unrelated patients with clinical symptoms of 21-hydroxylase
      deficiency, in a total of 112 independent alleles. CYP21A2 mutations were
      identified in 99.1% of the alleles. The most common point mutation was 1688G>T
      (25.9%). A previously unreported partial gene conversion, extending from exon 1
      to 7, was found in 16.1% of the alleles, in most cases associated to the mutation
      1688G>T in the other chromosome, and in patients with nonclassical CAH. Other
      three distinct partial gene conversions were also identified, with lower
      frequencies: one extends from exon 1 to 3 and the others from exons 3 to 7 and 3
      to 8. Two novel mutations were identified in two salt-wasting patients: a
      putative splicing mutation, IVS2+5G>A, and the transition 2557C>T, that gives
      rise to the nonsense mutation R445X. Seven point mutations and a partial gene
      conversion were responsible for 88 of the studied disease causing alleles, and
      the overall concordance between genotype and phenotype was 92.9%. With this study
      the molecular basis of CAH was characterized, for the first time, in Portuguese
      patients, providing useful results for clinicians in terms of prediction of
      disease severity, genetic and prenatal counseling.

PMID- 16427798
TI  - TNF gene polymorphisms are associated with reduced survival in severe Chagas'
      disease cardiomyopathy patients.
AB  - Chronic Chagas' disease cardiomyopathy (CCC) is the most important clinical
      outcome of infection by the parasite Trypanosoma cruzi, affecting 18 million
      individuals in Latin America. One-third of CCC patients develop heart failure due
      to end-stage dilated cardiomyopathy, and their survival is reduced by 50%
      compared to patients with other cardiomyopathies. Genetic susceptibility may play
      a role in the differential survival of severe CCC patients. Given the role of TNF
      alpha in the progression of heart failure, and the increased TNF-alpha plasma and
      heart tissue levels observed in these patients, we chose TNF as a candidate gene
      for increased mortality in severe CCC patients. We typed the TNFa microsatellite
      and the -308 TNF promoter polymorphism and then analyzed the survival curves of
      42 patients with severe ventricular dysfunction (left ventricular ejection
      fraction<or=40%) according to the presence of the TNF2 promoter allele or the
      TNFa2 microsatellite allele, both previously associated with high TNF-alpha
      production. Multivariate regression analysis (Cox proportional hazards model)
      revealed the TNF genotype and age of onset of severe CCC as independent
      predictors of mortality in severe CCC. We showed that patients positive for TNF2
      or TNFa2 alleles display a significantly shorter survival time compared to those
      carrying other alleles; the median survival times were 2.9 and 8 months,
      respectively (HR(adj)=2.28, p=0.020). We have identified for the first time a
      genetic factor related to reduced survival in severe Chagas' disease
      cardiomyopathy. The association of TNF genotype with earlier death in CCC should
      be taken into account when planning therapeutic intervention.

PMID- 16427799
TI  - Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme
      mRNA levels in type-2 diabetic mice.
AB  - Flavonoids have been identified as the antidiabetic components in a number of
      traditional ethnic remedies. However, the mechanisms whereby these compounds
      exert their hypoglycemic and hypolipidemic action in type-2 diabetes have rarely
      been investigated. Therefore, this study investigated the effect of the
      flavonoids hesperidin and naringin on glucose and lipid regulation in C57BL/KsJ
      db/db mice. Hesperidin and naringin both significantly increased the glucokinase
      mRNA level, while naringin also lowered the mRNA expression of
      phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver. In
      addition, the hepatic glucose transporter 2 protein expression was significantly
      reduced, while the expression of adipocyte glucose transporter 4 and hepatic and
      adipocyte peroxisome proliferator-activated receptor gamma were elevated in the
      hesperidin and naringin groups when compared with the control group. Furthermore,
      hesperidin and naringin effectively lowered the plasma free fatty acid and plasma
      and hepatic triglyceride levels, and simultaneously reduced the hepatic fatty
      acid oxidation and carnitine palmitoyl transferase activity. These changes were
      seemingly attributable to a suppression of the hepatic fatty acid synthase,
      glucose-6-phosphate dehydrogenase, and phosphatidate phosphohydrolase activities
      and an increase in the fecal triglycerides. The two flavonoids also led to a
      decrease in the plasma and hepatic cholesterol levels that may have been partly
      due to the decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA)
      reductase and acyl CoA: cholesterol acyltransferase (ACAT) activities and
      increased fecal cholesterol. Consequently, the current results suggest that
      hesperidin and naringin are beneficial for improving hyperlipidemia and
      hyperglycemia in type-2 diabetic animals by partly regulating the fatty acid and
      cholesterol metabolism and affecting the gene expression of glucose-regulating
      enzymes.

PMID- 16427800
TI  - In vivo cholesteryl ester selective uptake of mildly and standardly oxidized LDL
      occurs by both parenchymal and nonparenchymal mouse hepatic cells but SR-BI is
      only responsible for standardly oxidized LDL selective uptake by nonparenchymal
      cells.
AB  - In blood circulation, low density lipoproteins (LDL) can undergo modification,
      such as oxidation, and become key factors in the development of atherosclerosis.
      Although the liver is the major organ involved in the elimination of oxidized LDL
      (oxLDL), the identity of the receptor(s) involved remains to be defined. Our work
      aims to clarify the role of the scavenger receptor class B type I (SR-BI) in the
      hepatic metabolism of mildly and standardly oxLDL as well as the relative
      contribution of parenchymal (hepatocytes) and nonparenchymal liver cells with a
      special emphasis on CE-selective uptake. The association of native LDL and mildly
      or standardly oxLDL labeled either in proteins or in cholesteryl esters (CE) was
      measured on primary cultures of mouse hepatocytes from normal and SR-BI knock-out
      (KO) mice. These in vitro assays demonstrated that hepatocytes are able to
      mediate CE-selective uptake from both LDL and oxLDL and that SR-BI KO hepatocytes
      have a 60% reduced ability to selectively take CE from LDL but not towards mildly
      or standardly oxLDL. When lipoproteins were injected in the mouse inferior vena
      cava, parenchymal and nonparenchymal liver cells accumulated more CE than
      proteins from native, mildly and standardly oxLDL, indicating that selective
      uptake of CE from these lipoproteins occurs in vivo in these two cell types. The
      parenchymal cells contribute near 90% of the LDL-CE selective uptake and SR-BI
      for 60% of this pathway. Nonparenchymal cells capture mainly standardly oxLDL
      while parenchymal and nonparenchymal cells equally take up mildly oxLDL. An 82%
      reduction of standardly oxLDL-CE selective uptake by the nonparenchymal cells of
      SR-BI KO mice allowed emphasizing the contribution of SR-BI in hepatic metabolism
      of standardly oxLDL. However, SR-BI is not responsible for mildly oxLDL
      metabolism. Thus, SR-BI is involved in LDL- and standardly oxLDL-CE selective
      uptake in parenchymal and nonparenchymal cells, respectively.

PMID- 16427801
TI  - The efficacy of polyenylphosphatidylcholine for liver disease.

PMID- 16427802
TI  - Evaluation of a new molecular assay for detection of human immunodeficiency virus
      type 1 RNA, hepatitis C virus RNA, and hepatitis B virus DNA.
AB  - BACKGROUND: Rapid, sensitive, specific, and cost-effective screening of donated
      blood to prevent transmission of infectious agents remains challenging. In recent
      years, incorporation of nucleic acid testing for HIV-1 and HCV RNA improved blood
      safety by reducing the window period between infection and serologic detection.
      For HBV infection, this window period with most serologic assays is 50-60 days.
      Adding a nucleic acid test (NAT) for HBV DNA with existing NATs for HIV-1 and HCV
      RNA would further improve blood safety and blood screening efficiency. OBJECTIVE:
      To evaluate the Procleix Ultrio Assay for simultaneous detection of HIV-1 and HCV
      RNA and HBV DNA and corresponding discriminatory assays. STUDY DESIGN: The
      performance of these assays, which utilize the same technology and assay format
      as the Procleix HIV-1/HCV assay, was determined using relevant clinical specimens
      and analytical sensitivity and specificity panels. RESULTS: The Procleix Ultrio
      Assay demonstrated specificity of > or =99.5% in healthy donor blood specimens
      and in plasma containing potentially interfering substances or other blood-borne
      pathogens. Assay sensitivity demonstrated >95% detection of 100copies/mL,
      30IU/mL, and 15IU/mL for HIV-1 and HCV RNA, and HBV DNA, respectively. The assay
      detects all known HIV-1 subtypes and HCV and HBV genotypes and is highly
      reproducible. Statistical analysis using receiver operating characteristic plots
      demonstrated wide analyte cutoff values for each assay associated with assay
      specificity and sensitivity of > or =99.5%. CONCLUSIONS: In this investigational
      study, the Procleix Ultrio Assay sensitivity and specificity were similar to
      existing NATs used in blood-bank settings to detect HIV-1 and HCV RNA and
      provided equivalent sensitivity and specificity for detection of HBV DNA. Using
      this combination assay, blood safety may be improved and the multiplex format
      enhances blood screening efficiency. The throughput capability of this assay is
      compatible with large volume processing and the chemistry is adaptable to full
      automation.

PMID- 16427803
TI  - Docosahexaenoic acid-induced amelioration on impairment of memory learning in
      amyloid beta-infused rats relates to the decreases of amyloid beta and
      cholesterol levels in detergent-insoluble membrane fractions.
AB  - We investigated the effects of dietary administration of docosahexaenoic acid
      (DHA; C22:6n-3) on the levels of amyloid beta (A beta) peptide (1-40) and
      cholesterol in the nonionic detergent Triton 100 x-insoluble membrane fractions
      (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal
      model of Alzheimer's disease (AD) rats infused with A beta peptide (1-40) into
      the cerebral ventricle. The infusion increased the levels of A beta peptide and
      cholesterol in the DIFs concurrently with a significant increase in reference
      memory errors (measured by eight-arm radial-maze tasks) compared with those of
      vehicle rats. Conversely, the dietary administration of DHA to AD-model rats
      decreased the levels of A beta peptide and cholesterol in the DIFs, with the
      decrease being more prominent in the DHA-administered rats. Regression analysis
      revealed a significant positive correlation between A beta peptide and each of
      cholesterol, palmitic acid and stearic acid, and between the number of reference
      memory errors and each of cholesterol, palmitic, stearic and oleic acid;
      moreover, a significant negative correlation was observed between the number of
      reference memory errors and the molar ratio of DHA to palmitic plus stearic acid.
      These results suggest that DHA-induced protection of memory deficits in AD-model
      rats is related to the interactions of cholesterol, palmitic acid or stearic acid
      with A beta peptides in DIFs where DHA ameliorates these interactions.

PMID- 16427804
TI  - Evolution of a carbohydrate binding module into a protein-specific binder.
AB  - A carbohydrate binding module, CBM4-2, derived from the xylanase (Xyn 10A) of
      Rhodothermus marinus has been used as a scaffold for molecular diversification.
      Its binding specificity has been evolved to recognise a quite different target, a
      human monoclonal IgG4. In order to understand the basis for this drastic change
      in specificity we have further investigated the target recognition of the IgG4
      specific CBMs. Firstly, we defined that the structure target recognised by the
      selected CBM-variants was the protein and not the carbohydrates attached to the
      glycoprotein. We also identified key residues involved in the new specificity
      and/or responsible for the swap in specificity, from xylan to human IgG4.
      Specific changes present in all these CBMs included mutations not introduced in
      the design of the library from which the specific clones were selected. Reversion
      of such mutations led to a complete loss of binding to the target molecule,
      suggesting that they are critical for the recognition of human IgG4. Together
      with the mutations introduced at will, they had transformed the CBM scaffold into
      a protein binder. We have thus shown that the scaffold of CBM4-2 is able to
      harbour molecular recognition for either carbohydrate or protein structures.

PMID- 16427805
TI  - Fluorescence in situ hybridization with specific oligonucleotide rRNA probes
      distinguishes the sibling species Stylonychia lemnae and Stylonychia mytilus
      (Ciliophora, Spirotrichea).
AB  - Based on morphological and morphogenetic characters alone, the sibling species
      Stylonychia lemnae and Stylonychia mytilus, members of the Stylonychia mytilus
      complex, can hardly be distinguished. However, biochemical investigations of the
      isoenzyme pattern of different enzymes showed a distinct differentiation between
      these two species. In the last few years, fluorescence in situ hybridization
      (FISH) techniques have become a suitable and reliable tool for identification and
      differentiation of closely related species of protozoa, such as ciliates. To
      distinguish the sibling species, a set of specific oligonucleotide probes were
      developed. In the present study, the SSU rDNA of 7 clones of Stylonychia lemnae
      and 13 clones of Stylonychia mytilus, isolated from different geographic regions,
      were sequenced. Comparing all SSU rDNA sequences of both species, only one single
      difference within the whole gene was detected. Based on this difference, a set of
      two oligonucleotide probes, targeting the SSU rRNA of each species (Stylonychia
      mytilus and Stylonychia lemnae) was designed. These probes were successfully
      tested by applying the FISH techniques on preserved cells of different clones of
      both species.

PMID- 16427806
TI  - Ultrastructural study of the gametocytes and merogonic stages of Fallisia
      audaciosa (Haemosporina: Garniidae) that infect neutrophils of the lizard Plica
      umbra (Reptilia: Iguanidae).
AB  - Little is known regarding the ultrastructure of the genus Fallisia (Apicomplexa:
      Haemosporina: Garniidae). This report describes the fine structure of some
      developmental stages of Fallisia audaciosa that infect neutrophils in the
      peripheral blood of the Amazonian lizard Plica umbra (Reptilia: Iguanidae). The
      parasites lie within a parasitophorous vacuole and exhibit the basic structures
      of members of the Apicomplexa, such as the pellicle and the cytostome.
      Invaginations of the inner membrane complex were seen in the gametocytes and may
      be concerned with nutrition. The meronts were irregularly shaped before division,
      a feature unusual among members of the Apicomplexa. The unusual presence of a
      parasitic protozoan within neutrophils, in some way interfering with or
      modulating the microbicidal activity of such cells, is discussed.

PMID- 16427808
TI  - Meeting report: 8th International Phycological Congress at Durban, South Africa,
      August 13-19, 2005.

PMID- 16427809
TI  - A post-partum hemolytic-uremic-like-syndrome in a patient with pre-eclampsia:
      description of a clinical case.
AB  - HEMOLYTIC UREMIC SYNDROME POST-PARTUM: We describe a case of a 37-year-old woman
      admitted for severe renal failure to our hospital immediately after the delivery
      by caesarean section of twins. She had anuria, anemia, and moderate
      thrombocytopenia. A diagnosis of hemolytic-uremic syndrome was made. Plasma
      exchange was started, substitution was performed with fresh frozen plasma and
      eight consecutive plasmapheresis sessions were given. She received hydrocortisone
      and ACE inhibitors. After about fifteen days from the beginning of the illness,
      signs of active haemolysis disappeared and renal function was partially
      recovered. A genetic study demonstrated the absence of HF1 and MCP mutations but
      a polymorphic variant of the HF1 gene (C-257T promoter region). This polymorphism
      is strongly associated with non-diarrhoea-HUS (D-HUS). Post-partum HUS is quite a
      rare syndrome and has a poor outcome; however prompt diagnosis and efficacious
      therapy could save lives without clinical consequences. The excellent outcome of
      this patient seems to corroborate this concept.

PMID- 16427810
TI  - DNA strand break: structural and electrostatic properties studied by molecular
      dynamics simulation.
AB  - Due to their lethal consequences and a relatively high probability of
      introduction of repair errors and mutations, single and double strand breaks are
      among the most important and dangerous DNA lesions. However, the mechanisms of
      their recognition and repair processes are only poorly known at present. This
      work defines and analyzes a DNA with single strand break as a template study for
      future complex analyses of biologically serious double strand break damage and
      its enzymatic repair mechanisms. Besides a non-damaged DNA serving as a reference
      system with no surprising results, system with open valences of the atoms at the
      strand break ends as well as a system with filled valences were simulated. In
      both cases during the first few nanoseconds the broken ends of strand breaks are
      significantly exposed to the outside of the molecule. However, with increasing
      time, the system with single strand break with open valences is partially
      disrupted. On the contrary, the system with filled valences shows stable
      conformation with newly created hydrogen bond between the two strand break
      endings. Moreover, these endings are steadily situated in the inner part of the
      molecule, thus making the recognition and docking process of a repair enzyme more
      complicated in the case of filled valences.

PMID- 16427811
TI  - Double orifice mitral valve; a coincidental finding.
AB  - A double orifice mitral valve (DOMV) represents a rare congenital malformation
      characterised by two valve orifices with two separate subvalvular apparatus. This
      case demonstrates the necessity of careful imaging of the mitral valve apparatus,
      not only in patients with atrioventricular septal defects, but also in patients
      with congenital left obstructive heart disease.

PMID- 16427813
TI  - Spatial and temporal expression profile of pinin during mouse development.
AB  - SR and SR-related proteins are splicing regulators involved in embryo development
      in higher eukaryotes. Pinin (pnn) is a SR-related protein localized both within
      nucleus (nuclear pnn, N-pnn) and at desmosome of cell-cell adhesion (desmosomal
      pnn, D-pnn). To investigate the role of N-pnn during mouse embryo development, we
      examined its expression using Northern blot, real-time RT-PCR, immunostaining,
      and mRNA in situ hybridization (ISH). On Northern analysis, we found that pnn
      transcripts display two isoforms due to differential utilization of a
      polyadenylation site and exhibit tissue variable expression with thymus
      expressing the highest level of transcript. Analysis of pnn expression in mouse
      embryos revealed N-pnn expression starts from the two-cell fertilized egg stage
      and is ubiquitous at all stages of mouse embryo development. ISH and
      immunofluorescent staining of embryo cryosections showed that during mouse
      organogenesis N-pnn is highly expressed in the central nervous system. In
      addition, N-pnn was found to be highly expressed in the cortex region of thymus
      of E16.5 mouse fetus, while in the hepatic primordium the strongest signals were
      noted at E13.5 to E14.5 rather than at later developmental stages. Finally, we
      also determined the subcellular location of N-pnn in photoreceptors of developing
      retinas by nuclear fractionation and Western blot, because N-pnn displayed a
      staining pattern reminiscent of cytoplasmic proteins at the microscopic level in
      developing mouse photoreceptors. Altogether these data provide us with a better
      understanding of the tissue distribution pattern of N-pnn during mouse
      development.

PMID- 16427814
TI  - Electrochemical detection of scDNA cleavage in the presence of macrocyclic
      hexaaza-copper(II) complex.
AB  - The hexaaza macrocyclic copper(II) complex Cu(II)L(L=1,8-Dihydroxyethyl
      1,3,6,8,10,13-hexaazacyclotetradecane), which has octahedral structure similar to
      some natural complexes, is synthesized and purified. In this study, oxidative
      breakage DNA by the reaction of Cu(II)L with H2O2 and ascorbate has been
      investigated by gel electrophoresis experiments. In electrochemical experiments,
      the on scDNA-modified glassy carbon electrode(GCE) is cleaved by the Cu(II)L and
      redox changing of the metal catalyst without adding any other reagents. Above
      all, the need for concentration of scDNA is much lower than that of gel
      electrophoresis experiments and the process of the performance is easy.
      Furthermore, Cyclic Voltammetry (CV) and A.C. Impedance, which are performed to
      monitor scDNA cleavage at the scDNA-modified glassy carbon electrode (GCE), are
      fast, simple and highly efficient. The mechanism of the damage can be suggested:
      Fenton.

PMID- 16427815
TI  - Determination of agmatine in biological samples by capillary electrophoresis with
      chemiluminescence detection.
AB  - A fast and simple method based on capillary electrophoresis (CE) with
      chemiluminescence (CL) detection has been developed for the determination of
      agmatine, a recently identified neurotransmitter/modulator. The CE run time was
      approximately 2 min for each sample injected. CL detection employed a lab-built
      reaction flow cell and a photon counter. The CL reagents used were luminol and
      NaBrO. The optimized conditions for the CL detection were 5 x 10(-4)M luminol
      added to the CE running buffer and 5.0 x 10(-4)M NaBrO in 100 mM NaCO3-NaOH
      buffer solution at pH 12.5 introduced post column. Detection limit for agmatine
      was 4.3 x 10(-6)M (S/N=3). The precision (R.S.D.) on peak height (at 1 x 10(-5)M
      agmatine) and migration time were 3.7 and 2.5%, respectively. The present CE-CL
      method was evaluated with the determination of agmatine in tissue samples taken
      from rat brain, and rat and monkey stomachs. Samples were directly injected into
      the CE-CL system after the removal of proteins. A higher level of agmatine was
      detected in the stomach samples. Agmatine concentrations in the tissue samples
      taken from rat and monkey stomachs were similar at approximately 1950 ng/g wet
      tissue.

PMID- 16427812
TI  - Vascular calcium channels and high blood pressure: pathophysiology and
      therapeutic implications.
AB  - Long-lasting Ca(2+) (Ca(L)) channels of the Ca(v)1.2 gene family are
      heteromultimeric structures that are minimally composed of a pore-forming
      alpha(1C) subunit and regulatory beta and alpha(2)delta subunits in vascular
      smooth muscle cells. The Ca(L) channels are the primary pathways for voltage
      gated Ca(2+) influx that trigger excitation-contraction coupling in small
      resistance vessels. Notably, vascular smooth muscle cells of hypertensive rats
      show an increased expression of Ca(L) channel alpha(1C) subunits, which is
      associated with elevated Ca(2+) influx and the development of abnormal arterial
      tone. Indeed, blood pressure per se appears to promote Ca(L) channel expression
      in small arteries, and even short-term rises in pressure may alter channel
      expression. Membrane depolarization has been shown to be one stimulus associated
      with elevated blood pressure that promotes Ca(L) channel expression at the plasma
      membrane. Future studies to define the molecular processes that regulate Ca(L)
      channel expression in vascular smooth muscle cells will provide a rational basis
      for designing antihypertensive therapies to normalize Ca(L) channel expression
      and the development of anomalous vascular tone in hypertensive pathologies.

PMID- 16427816
TI  - The role of lysine residues 297 and 306 in nucleoside triphosphate regulation of
      E. coli CTP synthase: inactivation by 2',3'-dialdehyde ATP and mutational
      analyses.
AB  - Cytidine 5'-triphosphate synthase (CTPS) catalyzes the ATP-dependent formation of
      CTP from UTP using either NH3 or L-glutamine as the source of nitrogen. To
      identify the location of the ATP-binding site within the primary structure of E.
      coli CTPS, we used the affinity label 2',3'-dialdehyde adenosine 5'-triphosphate
      (oATP). oATP irreversibly inactivated CTPS in a first-order, time-dependent
      manner while ATP protected the enzyme from inactivation. In the presence of 10 mM
      UTP, the values of k(inact) and K(I) were 0.054 +/- 0.001 min(-1) and 3.36 +/-
      0.02 mM, respectively. CTPS was labeled using (2,8-3H)oATP and subsequently
      subjected to trypsin-catalyzed proteolysis. The tryptic peptides were separated
      using reversed-phase HPLC, and two peptides were identified using N-terminal
      sequencing (S(492)GDDQLVEIIEVPNH(506) and Y(298)IELPDAY(K(306)) in a 5:1 ratio).
      The latter suggested that Lys 306 had been modified by oATP. Replacement of Lys
      306 by alanine reduced the rate of oATP-dependent inactivation (k(inact) = 0.0058
      +/- 0.0005 min(-1), K(I) = 3.7 +/- 1.3 mM) and reduced the apparent affinity of
      CTPS for both ATP and UTP by approximately 2-fold. The efficiency of K306A
      catalyzed glutamine-dependent CTP formation was also reduced 2-fold while near
      wild-type activity was observed when NH3 was the substrate. These findings
      suggest that Lys 306 is not essential for ATP binding, but does play a role in
      bringing about the conformational changes that mediate interactions between the
      ATP and UTP sites, and between the ATP-binding site and the glutamine amide
      transfer domain. Replacement of the nearby, fully conserved Lys 297 by alanine
      did not affect NH3-dependent CTP formation, relative to wild-type CTPS, but
      reduced k(cat) for the glutaminase activity 78-fold. Our findings suggest that
      the conformational change associated with binding ATP may be transmitted through
      the L10-alpha11 structural unit (residues 297-312) and thereby mediate effects on
      the glutaminase activity of CTPS.

PMID- 16427817
TI  - High pressure reveals that the stability of interdimeric contacts in the R- and T
      state of HbA is influenced by allosteric effectors: Insights from computational
      simulations.
AB  - The molecular details of the mechanism of action of allosteric effectors on
      hemoglobin oxygen affinity are not clearly understood. The global allostery model
      proposed by Yonetani et al. suggests that the binding of allosteric effectors can
      take place both in the R and T states and that they influence oxygen affinity
      through inducing global tertiary changes in the subunits. Recently published high
      pressure studies yielded dissociation constants at atmospheric pressure that
      showed a stabilizing effect of heterotropic allosteric effectors on the dimer
      interface in the R state, and a more pronounced destabilizing effect in a T state
      model. In the present work, we report on computational modeling used to interpret
      the high pressure experimental data. We show structural changes in the hemoglobin
      interdimeric interfaces, indicative of a global tertiary structural change
      induced by the binding of allosteric effectors. We also show that the number of
      water molecules bound at the interface is significantly influenced by binding
      effectors in the T state in accordance with the experimental data. Our results
      suggest that the binding of effectors at definite sites leads to tertiary changes
      that propagate to the interfaces and results in overall structural re
      organizations.

PMID- 16427818
TI  - Analysis of the kinetic mechanism of arginyl-tRNA synthetase.
AB  - A kinetic analysis of the arginyl-tRNA synthetase (ArgRS) from Escherichia coli
      was accomplished with the goal of improving the rate equations so that they
      correspond more closely to the experimental results. 22 different steady-state
      kinetic two-ligand experiments were statistically analysed simultaneously. A
      mechanism and values for the ArgRS constants were found where the average error
      was only 6.2% and ranged from 2.5 to 11.2% in the different experiments. The
      mechanism included not only the normal activation and transfer reactions but also
      an additional step which may be a conformational change after the transfer
      reaction but before the dissociation of the product Arg-tRNA from the enzyme. The
      forward rate constants in these four steps were low, 8.3-27 s(-1), but the
      reverse rate constants of the activation and transfer reactions were considerably
      higher (230 and 161 s(-1)). Therefore, in the presence of even low concentrations
      of PP(i) and AMP, the rate limitation occurs at the late steps of the total
      reaction. AMP increases the rate of the ATP-PP(i) exchange reaction due to the
      high reverse rate in the transfer reaction. The rate equation obtained was used
      to calculate the steady-state enzyme intermediate concentrations and rates
      between the intermediates. Three different Mg2+ binding sites were required to
      describe the Mg2+ dependence. One of them was the normal binding to ATP and the
      others to tRNA or enzyme. The measured Mg2+ dependence of the apparent
      equilibrium constant of the ArgRS reaction was consistent with the Mg2+
      dependences of the reaction rates on the rate equation. Chloride inhibits the
      ArgRS reaction, 160 mM KCl caused a 50% inhibition if the ionic strength was kept
      constant with K-acetate. KCl strongly affected the K(m)(app) (tRNA) value. A
      difference was detected in the progress curves between the aminoacylation and ATP
      PP(i) exchange rates. When all free tRNA(Arg) had been used from the reaction
      mixture, the aminoacylation reaction stopped, but the ATP-PP(i) exchange
      continued at a lowered rate.

PMID- 16427819
TI  - The yeast prion protein Ure2: structure, function and folding.
AB  - The Saccharomyces cerevisiae protein Ure2 functions as a regulator of nitrogen
      metabolism and as a glutathione-dependent peroxidase. Ure2 also has the
      characteristics of a prion, in that it can undergo a heritable conformational
      change to an aggregated state; the prion form of Ure2 loses the regulatory
      function, but the enzymatic function appears to be maintained. A number of
      factors are found to affect the prion properties of Ure2, including mutation and
      expression levels of molecular chaperones, and the effect of these factors on
      structure and stability are being investigated. The relationship between
      structure, function and folding for the yeast prion Ure2 are discussed.

PMID- 16427820
TI  - Protein preparation, crystallization and preliminary X-ray crystallographic
      analysis of Smu.1475c from caries pathogen Streptococcus mutans.
AB  - The gene smu.1475c encodes a putative protein of 211 residues in Streptococcus
      mutans, a primary pathogen for human dental caries. In this work, smu.1475c was
      cloned into pET28a and expressed in good amount from the E. coli strain BL21
      (DE3). Smu.1475c protein was purified to homogeneity in a two-step procedure of
      Ni2+ chelating and size exclusion chromatography. Crystals were obtained by
      hanging-drop vapor-diffusion method and diffracted to 2.7 angstroms resolution.
      The crystal belongs to orthorhombic space group P2(1)2(1)2(1) with cell dimension
      of a = 68.3 angstroms, b = 105.9 angstroms, c = 136.2 angstroms. The asymmetric
      unit is expected to contain four molecules with solvent content of 49.4%.

PMID- 16427821
TI  - Native aortic valve insufficiency in patients with left ventricular assist
      devices.
AB  - Management of mild to moderate aortic insufficiency in patients with a left
      ventricular assist device remains controversial. We report 3 patients with aortic
      insufficiency and pulsatile left ventricular assist devices treated with a
      central aortic valve coapting suture. Two of the repairs have been durable for
      more than 1 year and aspirin appears to be sufficient anticoagulation.

PMID- 16427822
TI  - Further anatomical insights regarding the Ross procedure.

PMID- 16427823
TI  - Radiologic classification of small adenocarcinoma of the lung: radiologic
      pathologic correlation and its prognostic impact.
AB  - BACKGROUND: A new radiologic classification for small adenocarcinoma is necessary
      for discussions of limited surgical resection for peripheral lung cancer.
      METHODS: Between 1999 and 2003, 1,697 consecutive patients underwent pulmonary
      resection for lung cancer. Three hundred forty-nine of these patients with
      clinical stage IA lung cancer who had lung peripheral adenocarcinoma, 2 cm or
      less in size, were investigated retrospectively. Radiologic classification was
      based on the findings of thin-section computed tomographic scan such as the
      presence of solid and ground-glass opacity (GGO). Type 1 (n = 22), type 2 (n =
      26), type 3 (n = 25), and type 4 (n = 43) show a simple GGO, an intermediate
      homogeneous increase in density, a halo, and a mixed area of GGO and a solid,
      respectively. Type 5 (n = 54) shows a solid tumor with GGO, and type 6 (n = 179)
      shows a solid tumor. RESULTS: There was no difference in the maximum tumor
      dimension among the six groups. All but 1 patient had no lymph node metastases
      among type 1 to 4 tumors, whereas these were found in 5% and 24% of the patients
      with type 5 and 6 tumors, respectively. Lymphatic invasions were rarely found in
      patients with type 1 to 4 tumors (p < 0.001). CONCLUSIONS: Types 1, 2, 3, and 4
      are considered to be radiologic early adenocarcinoma of the lung, and their
      pathologic features were minimally invasive. On the other hand, type 5 and 6
      tumors could have lymph node metastases and are considered to be invasive
      adenocarcinoma. Although limited surgical resection may be enough for type 1 to 4
      tumors, anatomic pulmonary resection should be recommended for type 5 or 6 tumor.

PMID- 16427824
TI  - Invited commentary.

PMID- 16427825
TI  - Video-assisted thoracic surgery lobectomy: experience with 1,100 cases.
AB  - BACKGROUND: Although many video-assisted thoracic surgery (VATS) lobectomies have
      been performed over the 12 years since the first VATS lobectomy, controversies
      about the procedure remain regarding the safety and associated morbidity and
      mortality of that procedure. This series is reviewed to assess these issues.
      METHODS: Between 1992 and 2004, we performed 1,100 VATS lobectomies in 595 women
      (54.1%) and 505 men (45.9%), with a mean age of 71.2 years. Diagnoses were as
      follows: benign disease (53), pulmonary metastases (27), lymphoma (5), and lung
      cancer (1,015). Of the primary lung cancers, 641 (63.1%) were adenocarcinoma.
      With visualization on a monitor, anatomic hilar dissection and lymph node
      sampling or dissection were performed, primarily through a 5-cm incision without
      spreading the ribs. RESULTS: There were 9 deaths (0.8%), and none was
      intraoperative or due to bleeding; 932 patients had no postoperative
      complications (84.7%). Blood transfusion was required in 45 of 1,100 patients
      (4.1%). Length of stay was median 3 days (mean, 4.78). One hundred eighty
      patients (20%) were discharged on postoperative day 1 or 2. Conversion to a
      thoracotomy occurred in 28 patients (2.5%). Recurrence developed in the incisions
      in 5 patients (0.57%). In 2003, 89% of 224 lobectomies were performed with VATS.
      CONCLUSIONS: VATS lobectomy with anatomic dissection can be performed with low
      morbidity and mortality rates. The risk of intraoperative bleeding or recurrence
      in an incision seems minimal.

PMID- 16427827
TI  - Sublobar resection with brachytherapy versus lobectomy for stage Ib nonsmall cell
      lung cancer.
AB  - BACKGROUND: We have previously shown that intraoperative brachytherapy decreases
      the local recurrences associated with sublobar resections for small stage Ia
      nonsmall-cell lung cancer (NSCLC). In this report, we present the outcomes of
      sublobar resection with brachytherapy compared with lobectomy in patients with
      stage Ib tumors. METHODS: We retrospectively reviewed 167 stage Ib NSCLC
      patients: 126 underwent lobectomy and 41 sublobar resection with (125)I
      brachytherapy over the resection staple line. Endpoints were perioperative
      outcomes, incidence of recurrence, and disease-free and overall survival.
      RESULTS: Patients undergoing sublobar resections had significantly worse
      preoperative pulmonary function. Hospital mortality, nonfatal complications, and
      median length of stay were similar in the two groups. Median follow-up was 25.1
      months. Local recurrence in sublobar resection patients was 2 of 41 (4.8%),
      similar to the lobectomy group: 4 of 126 (3.2%; p = 0.6). At 4 years, both groups
      had equivalent disease-free survival (sublobar group, 43.0%; median, 37.7 months;
      and lobectomy group, 42.8%; median 41.8 months, p = 0.57) and overall survival
      (sublobar group, 54.1%; median, 50.2 months; and lobectomy group, 51.8%; median,
      56.9 months; p = 0.38). CONCLUSIONS: Sublobar resection with brachytherapy
      reduced local recurrence rates to the equivalent of lobectomy in patients with
      stage Ib NSCLC, and resulted in similar perioperative outcomes and disease-free
      and overall survival, despite being used in patients with compromised lung
      function. We recommend the addition of intraoperative brachytherapy to sublobar
      resections in stage Ib patients who cannot tolerate a lobectomy.

PMID- 16427826
TI  - Results of initial operations in non-small cell lung cancer patients with single
      level N2 disease.
AB  - BACKGROUND: There is still debate regarding the use of surgery in the management
      of non-small cell lung cancer patients with N2 disease. The primary aim of the
      present study was analysis of the results of initial operations in non-small cell
      lung cancer patients with single-level N2 disease. METHODS: Ninety-four patients
      with the disease who underwent initial surgery consisting of complete resection
      of the primary site plus systematic lymphadenectomy were examined. We also
      immunohistochemically examined lymphatic vessel density and vascular endothelial
      growth factor-C expression. RESULTS: The overall 5- and 10-year survival rates
      for the 94 patients were 27.1% and 12.1%, respectively, with a median survival of
      22 months. When stratified by skipping status, the 5-year survival rates for the
      patients in skip-N2 and non-skip-N2 groups were 33.4% and 19.8%, respectively (p
      = 0.0189). Skip metastasis, T factor, subcarinal lymph node metastasis, and
      adjuvant chemotherapy were recognized as independent prognostic indicators. In
      both skip-N2 and non-skip-N2 groups, distant relapse was the dominant pattern of
      recurrence. Although the peritumoral lymphatic vessel density was associated with
      vascular endothelial growth factor-C expression in tumors, the lymphangiogenic
      profile appeared to be different between skip-N2 and non-skip-N2 tumors,
      suggesting different nodal metastatic process. CONCLUSIONS: Lung cancer patients
      with single-level N2 disease are an oncologically heterogeneous cohort. Although
      further studies involving randomized comparisons are required, the poor outcomes
      found here indicate that the initial operation has yet to be validated for
      patients with this disease.

PMID- 16427828
TI  - Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell
      lung cancer.
AB  - BACKGROUND: Recent clinical trials suggest that adjuvant chemotherapy provides a
      survival advantage for patients with completely resected nonsmall-cell lung
      cancer (NSCLC) yet many patients receive chemotherapy without benefit. Tumor in
      vitro resistance to antineoplastic agents is highly predictive of clinical
      unresponsiveness to chemotherapy for some cancers; however, little is known of
      the prevalence of extreme chemotherapy drug resistance for human NSCLC tumors.
      Chemoresistance testing may be a way to predict treatment failure, choose
      alternative agents, and to avoid unnecessary chemotherapy toxicity. This study
      describes the prevalence of in vitro chemotherapy resistance in NSCLC patient
      tumor cultures. METHODS: A total of 3,042 NSCLC specimens were cultured in a
      proliferation assay and tested for resistance to carboplatin, cisplatin,
      doxorubicin, etoposide, gemcitabine, navelbine, paclitaxel, taxotere, or
      topotecan. The percentage of cell-growth inhibition measured by 3H-Thymidine
      uptake was used to determine extreme drug resistance, intermediate drug
      resistance, or low drug resistance. RESULTS: Extreme drug resistance or
      intermediate drug resistance to carboplatin was found in 1,056 of 1,565 NSCLC
      cultures (68%), to cisplatin in 1,409 of 2,227 (63%), to doxorubicin in 1,101 of
      1,471 (75%), to etoposide in 1,581 of 2,505 (63%), to gemcitabine in 594 of 823
      (72%), to navelbine in 603 of 1,444 (42%), to paclitaxel in 689 of 1,706 (40%),
      to taxotere in 273 of 521 (52%), and to topotecan in 280 of 896 (31%).
      CONCLUSIONS: Chemotherapy resistance is prevalent among NSCLC clinical cell
      cultures. This may account for the small survival seen with empiric adjuvant
      chemotherapy. The use of viable tumor culture for in vitro chemoresistance
      testing should be considered when formulating a plan of adjuvant therapy for
      resected NSCLC. Future trials comparing patient survival after tailored versus
      empiric adjuvant therapy appear justified.

PMID- 16427829
TI  - Nodal involvement at the time of pulmonary metastasectomy: experiences in 245
      patients.
AB  - BACKGROUND: Although routine systematic mediastinal and hilar lymph node
      dissection contemporary with pulmonary metastasectomy has not been uniformly
      performed in many thoracic surgical centers, the value of this procedure needs to
      be investigated. METHODS: Between 1996 and 2001, 245 patients (157 men, 88 women)
      underwent pulmonary resection of metastatic colorectal carcinoma, sarcoma, and
      renal cell carcinoma. Generally, systematic mediastinal and hilar lymph node
      dissection was performed concurrently with pulmonary metastasectomy. Patients
      were assessed for patterns of lymph node metastases. The frequency of lymph node
      involvement was determined. Patients and tumor characteristics were assessed to
      ascertain whether certain factors were likely to predict lymph node spread.
      RESULTS: Of the 245 patients (328 primary thoracic procedures), 165 had no lymph
      node involvement, 45 had pulmonary and hilar metastases, 22 had pulmonary, hilar,
      and mediastinal metastases, and 13 had only mediastinal involvement without
      pulmonary and hilar spread. Patients with more than one pulmonary metastasis or
      metachronous disease were more likely to have thoracic lymph node metastases. The
      risk for mediastinal lymph node involvement was even more likely for patients who
      had already pulmonary or hilar lymph node spread; the odds ratios (with 95%
      confidence intervals) were 1.30 (0.71 to 2.36), 1.32 (0.59 to 2.99), and 5.87
      (2.73 to 12.6), respectively. Median survival for the group of patients after
      complete resection was 54.8 months (95% CI: 40.9 to 68.7); and for the patients
      with no lymph node involvement, it was 63.9 months (95% CI: 45.3 to 82.6); with
      N1 disease, 32.7 months (95% CI: 9.2 to 56.2); and with N1 + N2 disease, 20.6
      months (95% CI: 5.1 to 36.1). The log-rank test revealed significance between N0
      and N1 (p = 0.018) and N0 versus N1, 2 (p = 0.001). CONCLUSIONS: We conclude that
      systematic mediastinal and hilar lymph node dissection contemporary with
      pulmonary metastasectomy offers a further understanding of metastatic disease and
      provides important information for complete surgical staging.

PMID- 16427831
TI  - Ex vivo evaluation of nonacceptable donor lungs.
AB  - BACKGROUND: Only a minority of the potential candidates for lung donation are
      considered suitable, using current evaluation methods. A new method for ex vivo
      evaluation, with the potential for reconditioning of marginal and nonacceptable
      lungs, has been developed. This is a report of the ex vivo evaluation of six
      donor lungs deemed nonacceptable (arterial oxygen pressure less than 40 kPa) by
      the Scandiatransplant, Eurotransplant, and UK transplant organizations. METHODS:
      The lungs are perfused ex vivo with Steen solution, a lung evaluation
      preservation solution, mixed with red blood cells to a hematocrit of 15%. This
      extracellular solution is designed to have an optimal colloid osmotic pressure so
      that physiologic pressure and flow can be maintained without development of
      pulmonary edema. An oxygenator connected to the extracorporeal circuit maintains
      a normal mixed venous blood gas level in the perfusate. The lungs are ventilated
      and evaluated through analyses of pulmonary vascular resistance, oxygenation
      capacity, and arterial carbon dioxide pressure minus end-tidal carbon dioxide
      difference. RESULTS: The arterial oxygen pressure (inspired oxygen fraction, 1.0)
      increased from 27 kPa (range, 17 to 34 kPa) in situ in the organ donor at the
      referring hospital to 57 kPa (range, 39 to 66 kPa) during the ex vivo evaluation.
      The pulmonary vascular resistance varied from 3.2 to 5.7 Wood units, and the
      arterial carbon dioxide pressure minus end-tidal carbon dioxide difference was in
      the range of 1 to 2.5 kPa. CONCLUSIONS: The arterial oxygen pressure improves
      significantly in this model. This ex vivo evaluation model is a valuable addition
      to the armamentarium in finding acceptable lungs in a donor population with
      inferior arterial oxygen pressure values.

PMID- 16427830
TI  - Experience with the "da Vinci" robotic system for thymectomy in patients with
      myasthenia gravis: report of 33 cases.
AB  - BACKGROUND: Our initial experience in applying robotic-assisted technologies for
      the treatment of myasthenia gravis (MG) in patients without thymoma is reported.
      METHODS: from April 2002 to October 2004, 33 patients (24 females and 9 males;
      mean age, 41 years), with clinical nonthymomatous myasthenia gravis, underwent
      robotic thoracoscopic thymectomy using the "da Vinci" (Intuitive Surgical, Inc,
      Mountain View, CA) system and adopting a 3 port, left-sided approach. RESULTS:
      Mean operative time was 120 minutes. No intraoperative complications or surgical
      mortality is reported and postoperative complications occurred in two patients
      (6%). Mean hospital stay was 2.6 days (range, 2-14 days). Histologic analysis of
      surgical specimens revealed 23 hyperplasia, 4 normal thymus, 4 atrophy, and 2
      thymomas; in 12 patients (36.3%) ectopic thymic tissue was found. Follow-up
      evaluation of the first 24 patients (mean, 23.8 months; range, 12-31 months)
      showed that 4 patients (16.7%) had complete remission and 18 (75%) had
      significant clinical improvement for a global benefit rate of 91.7%. CONCLUSIONS:
      In patients with MG, robot-assisted thymectomy can be performed safely and
      efficiently. The improved visualization and dexterity of this instrument and its
      advanced technology may facilitate the minimally invasive approach to the thymus.
      We prefer to use the left-sided approach because it provides an enhanced
      visualization of the aortic window and it reduces the probability of phrenic
      nerves injury. A longer follow-up is necessary to verify long-term clinical
      results.

PMID- 16427832
TI  - Invited commentary.

PMID- 16427833
TI  - Nonoperative treatment of 15 benign esophageal perforations with self-expandable
      covered metal stents.
AB  - BACKGROUND: Spontaneous or iatrogenic esophageal perforations after endoscopic
      procedures are potentially life-threatening events with a considerable mortality
      rate. The aim of this study was to demonstrate that a nonoperative endoscopic
      treatment with self-expanding metal stents may have a lower morbidity and
      mortality rate compared with surgical treatment. METHODS: A nonrandomized
      observational study was conducted with 15 consecutive patients between January
      1997 and June 2004. Benign spontaneous and iatrogenic esophageal perforations
      after endoscopic procedures were treated with self-expandable metal stents.
      RESULTS: Seven patients (group 1) underwent stent insertion with an average time
      delay of 45 minutes. In 8 patients (group 2), the median delay was 123 hours. All
      patients in group 1 had an uneventful recovery and left hospital 5 days (range, 3
      to 9) after stent insertion. One patient in group 2 (1 of 8) died of pneumonia
      after 6 days. In any other cases, perforations healed successfully after stent
      placement, but the clinical course was generally complicated with sepsis and
      multiple organ failure. The average hospital stay was 44 days (range, 15 to 70).
      CONCLUSIONS: Immediate insertion of a self-expandable metal stent enables an
      excellent outcome with minimal mortality and morbidity without the need for
      operation. Even in cases of old esophageal perforations, sealing with self
      expandable metal stents is still a good option although the clinical course is
      much less impressive than in early treated perforations.

PMID- 16427834
TI  - Invited commentary.

PMID- 16427835
TI  - Hypothermic low-flow cardiopulmonary bypass impairs pulmonary and right
      ventricular function more than circulatory arrest.
AB  - BACKGROUND: Hypothermic circulatory arrest (HCA) is used during surgical
      treatment of certain congenital heart defects. The possibility of ischemic
      neurologic injury associated with HCA has led some surgeons to use low-flow
      cardiopulmonary bypass (CPB) during the hypothermic interval (hypothermic low
      flow [HLF]). This study investigates the inflammatory response to HCA and HLF,
      and reports the consequences of this response on pulmonary and right ventricular
      function. METHODS: Piglets (3.1 to 6.6 kg) were cooled to 16 degrees to 18
      degrees C using CPB, and randomized: HCA for 60 minutes (n = 7), or HLF (50
      cc.kg(-1).min(-1)) for 60 minutes (n = 6). The piglets were rewarmed to 36
      degrees C and weaned from CPB. Serum tumor necrosis factor-alpha (TNF-alpha)
      concentration, percent lung water, and pulmonary and cardiac function were
      measured before and after CPB. RESULTS: Tumor necrosis factor-alpha was higher
      after HLF (2,990.5 +/- 884.5 pg/mL), compared with HCA (347.6 +/- 89.2 pg/mL; p =
      0.03). The percent lung water was higher after HLF (84.8% +/- 0.3%) than HCA
      (82.0% +/- 0.4%; p < 0.001). The alveolar to arterial oxygen gradient was worse
      after HLF (457 +/- 42 mm Hg) than HCA (285.8 +/- 45 mm Hg; p = 0.02). Pulmonary
      vascular resistance was greater after HLF (36.08 +/- 8.28 mm Hg.mL(-1).m(-2).min(
      1)) than HCA (14.55 +/- 3.46 mm Hg. mL(-1).m(-2).min(-1); p = 0.049). The right
      ventricular pressure waveform peak derivative, corrected for systolic pulmonary
      artery pressure, was lower after HLF (14.1 +/- 1.4 sec(-1)), than HCA (23.8 +/-
      2.7 sec(-1); p = 0.01). CONCLUSIONS: Hypothermic low flow extends exposure to
      CPB, and is associated with an increased inflammatory response compared with HCA.
      The greater inflammatory response after HLF may result in substantial
      nonneurologic morbidity in the postoperative period, demonstrated by pulmonary
      and right ventricular dysfunction. Interventions that attenuate the inflammatory
      response to CPB may prevent pulmonary and right ventricular dysfunction after
      HLF.

PMID- 16427836
TI  - Prosthesis-patient mismatch after aortic valve replacement: impact of age and
      body size on late survival.
AB  - BACKGROUND: The purpose of this study was to identify patient subgroups in which
      prosthesis-patient mismatch most influenced late survival. METHODS: Over a 12
      year period, 1,400 consecutive patients underwent bioprosthetic (933 patients) or
      mechanical (467) aortic valve replacement. Prosthesis-patient mismatch was
      defined as prosthetic effective orifice area/body surface area less than 0.75
      cm2/m2 and was present with 11% mechanical and 51% bioprosthetic valves. RESULTS:
      With bioprosthetic valves, prosthesis-patient mismatch was associated with
      impaired survival for patients less than 60 years old (10-year: 68% +/- 7%
      mismatch versus 75% +/- 7% no mismatch, p < 0.02) but not older patients (p =
      0.47). Similarly, with mechanical valves, prosthesis-patient mismatch was
      associated with impaired survival for patients less than 60 years old (10-year:
      62% +/- 11% versus 79% +/- 4%, p < 0.005) but not older patients (p = 0.26). For
      small patients (body surface area less than 1.7 m2), prosthesis-patient mismatch
      did not impact survival with bioprosthetic (p = 0.32) or mechanical (p = 0.71)
      valves. For average-size patients (body surface area 1.7 to 2.1 m2), prosthesis
      patient mismatch was associated with impaired survival with both bioprosthetic (p
      < 0.05) and mechanical (p < 0.005) valves. For large patients (body surface area
      greater than 2.1 m2), prosthesis-patient mismatch was associated with impaired
      survival with mechanical (p < 0.04) but not bioprosthetic (p = 0.40) valves.
      CONCLUSIONS: Prosthesis-patient mismatch had a negative impact on survival for
      young patients, but its impact on older patients was minimal. In addition,
      although prosthesis-patient mismatch was not important in small patients,
      prosthesis-patient mismatch negatively impacted survival for average-size
      patients and for large patients with mechanical valves.

PMID- 16427837
TI  - Acquired and reversible von Willebrand disease with high shear stress aortic
      valve stenosis.
AB  - BACKGROUND: Severe aortic valve stenosis is relatively more prevalent in patients
      with repeated bleeding episodes. The goal of the present study was to determine
      the effect of aortic valve replacement on von Willebrand factor levels in
      patients with aortic stenosis. METHODS: von Willebrand factor levels were
      assessed by using immunoblotting electrophoresis techniques before and 1 month
      after surgery in 29 consecutive patients with severe aortic valve stenosis.
      RESULTS: Eight of 29 patients reported episodes of bleeding, including three
      episodes of major bleeding, in the 6 months before surgery. None of the patients
      were receiving anticoagulation therapy. Although there was no difference in
      platelet count before and after surgery, von Willebrand factor levels were
      significantly greater at 1 month after surgery (p = 0.05) when compared with
      preoperative values. Further, von Willebrand factor levels were significantly
      lower in patients with aortic valve prosthesis mismatch than in those patients
      without this phenomenon (p < 0.05). Electrophoresis experiments showed a deficit
      in large multimers of von Willebrand factor preoperatively but not
      postoperatively, except for in those patients with aortic valve prosthesis
      mismatch. CONCLUSIONS: In conclusion, valve replacement can result in increases
      in von Willebrand factor in patients with aortic valve stenosis.

PMID- 16427838
TI  - The Ross procedure: new insights into the surgical anatomy.
AB  - BACKGROUND: The precise knowledge of regional anatomical details is of utmost
      importance specially in complex procedures such as the Ross operation. This
      anatomical study offers a critical approach regarding the advantages, limits, and
      precautions for this procedure. METHODS: Using dissection techniques,
      magnifications up to x6 and nontraditional approaches, 68 fixed normal heart
      specimens were studied over a 2-year period. The details of surgical relevance
      such as the boundaries and relations of the pulmonary and aortic roots, their
      vascularization, and the number and distribution of the septal arteries are
      described. RESULTS: The aortic and pulmonary roots include interdependent
      elements functioning in a coordinated manner and establishing important relations
      with adjacent structures. Both coronary arteries vascularize the arterial roots.
      The infundibular branches from the right coronary artery are larger and more
      constant. The septal arteries establish important relations with the pulmonary
      infundibulum but their contribution to its vascularization is negligible. In this
      series, the main septal artery was the second, showing the longest
      retroinfundibular course. However, no constant relation was found between this
      vessel and the intraventricular landmarks. CONCLUSIONS: A novel approach was used
      by performing nontraditional dissections of the arterial roots and by studying
      their vascularization The depicted details are useful to the surgeon specializing
      in the Ross procedure and represent the basis for further research.

PMID- 16427839
TI  - Mitral valve replacement with Ross II technique: initial experience.
AB  - BACKGROUND: Pulmonary autograft mitral valve replacement (PA-MVR) was introduced
      clinically by Ross in 1967, but has been rarely utilized in North America and
      Europe. The aim of this study is to review our early experience with PA-MVR.
      METHODS: Since June 2002, 8 patients (7 female and 1 male) between 12 to 46 years
      of age with outgrown mechanical valves (n = 3) failed MV repair for rheumatic or
      congenital MV disease (n = 4) and irreparable bileaflet myxoid prolapse (n = 1),
      underwent PA-MVR. The pulmonary autograft was harvested and replaced using a
      pulmonary homograft. The autografts were mounted within a woven Dacron graft 6-8
      mm greater in diameter than the autograft annulus diameter on a preoperative
      echocardiogram. The graft's external surface was covered with fresh autologous
      pericardium. RESULTS: There were no deaths. Intraoperative echocardiography
      confirmed a mean MV gradient of 4 mm Hg with trivial (n = 7) or mild (n = 1)
      regurgitation. Follow-up (range, 13 to 36 months) echocardiography in 4 patients
      showed no increase in MV gradient or regurgitation. One patient with severe
      myxoid degeneration and one patient with rheumatic disease, both with systemic
      hypertension, developed progressive regurgitation due to stretching of a single
      autograft leaflet producing prolapse. One patient developed a moderate gradient
      due to retention of excessive native mitral leaflet and subannular chordal
      tissue. Three of 4 patients have required PA-MVR replacement with mechanical
      valves 6 to 14 months post-PA-MVR. One asymptomatic patient with mild to moderate
      mitral regurgitation is being followed after treatment of her systemic
      hypertension. CONCLUSIONS: Pulmonary autograft mitral valve replacement offers
      selected patients a potentially lifelong autologous valve without the need for
      long-term anticoagulation. The PA-MVR technique deserves careful consideration in
      younger patients in sinus rhythm. Postoperative systemic hypertension should be
      treated aggressively to prevent excessive stress on the pulmonary autograft
      particularly in the early postoperative months.

PMID- 16427840
TI  - Atrial incision affects the incidence of atrial tachycardia after mitral valve
      surgery.
AB  - BACKGROUND: Atrial fibrillation is common after mitral valve surgery. We do not
      know the incidence of atrial tachycardia and how it depends on the surgical
      approach used. METHODS: The subjects of the study were 213 consecutive patients
      who had surgery for mitral valve disease from January 1, 2001, through January
      26, 2004. The surgeons used either the superior transseptal approach (69
      patients, group A) or left atrial approach (144 patients, group B). An
      investigator, blinded for the approach used, analyzed all 12-lead
      electrocardiograms taken during the admission after the operation. The data were
      analyzed using the Cox regression analysis as time from the operation until
      documentation of atrial tachycardia or atrial fibrillation on a 12-lead
      electrocardiogram. Hazard ratio (95% confidence interval) is reported. RESULTS:
      The superior transseptal approach (2.0 [1.1 to 3.5], p = 0.023), age 60 years or
      more (2.3 [1.2 to 4.6], p = 0.015), and male sex (2.6 [1.3 to 5.2], p = 0.007)
      were independent predictors of atrial tachycardia. Age 60 years or more was the
      only independent predictor of atrial fibrillation (2.0 [1.2 to 3.3], p = 0.007).
      Although atrial tachycardia was less frequent than atrial fibrillation in group B
      (p < 0.001), atrial tachycardia was as common as atrial fibrillation in group A
      (p = 0.149). CONCLUSIONS: The superior transseptal approach has a higher risk of
      atrial tachycardia than the left atrial approach. Atrial tachycardia has
      different predictors than atrial fibrillation and constitutes a significant
      problem, especially after the superior transseptal approach. These results
      emphasize the need to distinguish between atrial tachycardia and atrial
      fibrillation-two entities with different pathophysiology, therapy, and also
      epidemiology.

PMID- 16427841
TI  - Prediction and incidence of atrial fibrillation after aortic arch repair.
AB  - BACKGROUND: Although atrial fibrillation is often associated with increased
      morbidity after open heart surgery, neither the incidence nor the clinical
      consequences of atrial fibrillation after aortic surgery has been well
      investigated. The goal of this study was to elucidate the risks for incidence of
      postoperative atrial fibrillation after aortic arch repair. METHODS: From January
      1993 to February 2004, 483 patients with atherosclerotic aortic arch aneurysm (n
      = 327) or aortic dissection (n = 156) underwent total aortic arch repair. All
      patients operated on as elective, urgent, or emergency aortic arch repair were
      included. One hundred sixteen patients received surgery on an emergency basis
      because of rupture or acute type A dissection. Twenty-four patients had atrial
      fibrillation preoperatively. Potential predictors of postoperative atrial
      fibrillation were estimated by a logistic regression model. RESULTS: The
      incidence of postoperative, new onset of atrial fibrillation was 52.7% (242 of
      459). The length of postoperative hospital stay was longer in patients with
      postoperative atrial fibrillation (48 +/- 52 days) than in patients without it
      (35 +/- 29 days; p = 0.001). The length of intensive care unit stay was also
      longer in patients with postoperative atrial fibrillation (12.1 +/- 23.2) than in
      patients without it (6.2 +/- 8.8; p = 0.002). Advanced age (p = 0.007; odds ratio
      = 1.34; 95% confidence interval: 1.14 to 1.62, per 10 years) was the only risk
      factor that correlated with postoperative new onset of atrial fibrillation.
      CONCLUSIONS: Atrial fibrillation was not uncommon after aortic arch repair.
      Advanced age was the only preoperative risk factor for postoperative atrial
      fibrillation.

PMID- 16427842
TI  - Cerebral microembolization during antegrade selective cerebral perfusion.
AB  - BACKGROUND: This study quantified the number of intraoperative microemboli in
      patients undergoing aortic arch surgery using selective cerebral perfusion (SCP)
      in comparison with those in patients undergoing ascending aortic replacement
      without circulatory arrest and SCP. METHODS: A transcranial Doppler monitoring of
      the medial cerebral artery was performed in 15 patients undergoing proximal arch
      replacement with SCP (SCP group) and 15 patients undergoing replacement of the
      ascending aorta (control group). RESULTS: There was no significant difference in
      the high-intensity transient signal counts between the SCP group and the control
      group at any phase. In the SCP group, 4.8% of microemboli occurred during cross
      clamping, and only 0.6% occurred during SCP. In the control group, 4.6% occurred
      during cross-clamping. Most microemboli occurred after removing the cross-clamps
      in both groups; 92.2% in the SCP group and 92.1% in the control group.
      CONCLUSIONS: The present study demonstrated that outbreak frequency of
      microemboli during SCP was very low, and thus implies that the risk of embolic
      event that may be caused by SCP is very low.

PMID- 16427843
TI  - Pericardiectomy for constrictive pericarditis: a clinical, echocardiographic, and
      hemodynamic evaluation of two surgical techniques.
AB  - BACKGROUND: This study was designed to compare the outcomes after total versus
      partial pericardiectomy clinically, echocardiographically, and hemodynamically.
      METHODS: Three hundred ninety-five patients undergoing pericardiectomy for
      constrictive pericarditis between January 1985 and December 2004 were studied.
      Age was 10 months to 71 years (mean, 25.1 +/- 13.4 years). Three hundred thirty
      eight patients (85.6%) underwent total pericardiectomy (group I), and 57 patients
      (14.4%) underwent partial pericardiectomy (group II). RESULTS: Operative and late
      mortality rates were 7.6% and 4.9%, respectively. Preoperative high right atrial
      pressure, hyperbilirubinemia, renal dysfunction, atrial fibrillation, pericardial
      calcification, thoracotomy approach, and partial pericardiectomy were significant
      risk factors for death. The risk of death was 4.5 times higher (95% confidence
      interval: 2.05 to 9.75) in patients undergoing partial pericardiectomy. At a mean
      follow-up of 17.9 +/- 0.3 years (95% confidence interval: 17.3 to 18.6),
      actuarial survival was 83.8% +/- 0.04% in group I and 73.9% +/- 0.06% in group II
      (p = 0.004). At their last follow-up, 96.3% survivors of group I and 79.1%
      survivors of group II were in New York Heart Association class I/II (p < 0.001).
      CONCLUSIONS: Total pericardiectomy is associated with lower perioperative and
      late mortality, and confers significant long-term advantage by providing superior
      hemodynamics that appear to be independent of the etiology of constrictive
      pericarditis.

PMID- 16427844
TI  - Invited commentary.

PMID- 16427845
TI  - Racial and ethnic disparities in care: the perspectives of cardiovascular
      surgeons.
AB  - BACKGROUND: Although racial/ethnic disparities in care are well documented,
      particularly for cardiac care, we know little about what cardiac surgeons think
      about them. For educational efforts to be effective in helping physicians address
      disparities, they must consider providers' knowledge and beliefs about the
      underlying causes of the disparities. METHODS: We conducted a survey in 2004 to
      assess cardiologists' and cardiac surgeons' knowledge of racial/ethnic
      disparities in cardiovascular care and their perceptions about the underlying
      causes. Respondents were recruited from the membership of four cardiovascular
      professional associations. This paper focuses on cardiovascular surgeons'
      responses (n = 208). RESULTS: Forty-four percent of cardiovascular surgeons
      thought that, among patients with cardiac risk factors, black patients were not
      as likely as white patients to receive cardiac diagnostic tests and procedures.
      Additionally, 30% thought that black patients were not as likely as white
      patients to receive therapeutic tests and procedures. However, only 13% agreed
      that cardiac care disparities occur "often" or "somewhat often" based on
      patients' race/ethnicity, independent of their insurance and education. Only 3%
      thought disparities were likely to occur in their clinical setting. Respondents
      appeared more likely to endorse patient factors (eg, health behaviors or
      treatment adherence) than system or provider (eg, miscommunication or continuity
      of care) factors as reasons for disparities. CONCLUSIONS: Although some surgeons
      acknowledge that racial/ethnic disparities in cardiac care occur, very few agree
      that they occur often, independent of patients' characteristics. Educational
      efforts tailored to local care settings, such as reviewing quality of care data
      on patients of different races/ethnicities within a clinic/hospital, may
      effectively inform all physicians of these disparities.

PMID- 16427846
TI  - Validation of the 2000 Bernstein-Parsonnet score versus the EuroSCORE as a
      prognostic tool in cardiac surgery.
AB  - BACKGROUND: Intradepartmental and interdepartmental benchmarking requires scoring
      systems with reliability (calibration) and stability over the complete spectrum
      of periprocedural risk. The aim of this single-center study was to assess the
      performance of the 2000 Bernstein-Parsonnet risk stratification model in cardiac
      surgery, by itself and against the EuroSCORE. METHODS: A prospective
      observational design was used. The study group consisted of 1,639 consecutive
      patients of mean age 64.6 +/- 12.04 years who underwent elective or emergency
      cardiac surgery from January 2003 to June 2004. The probabilities of hospital
      death were estimated with the 2000 Bernstein-Parsonnet and EuroSCORE algorithms.
      The correlation of predicted and observed mortality was compared between the two
      models, and score validity was assessed by calculating the area under the
      receiver operating characteristic (ROC) curve. RESULTS: The patients were
      stratified into five risk groups according to their scores in the two models. For
      the 2000 Bernstein-Parsonnet model, findings were as follows: score 0-10:
      predicted mortality 0%-2.2%, observed mortality 0.6%; score 10.5-20: predicted
      2.3%-4.7%, observed 2.3%; score 20.5-30: predicted 4.8%-10%, observed 6.7%; score
      30.5-40: predicted 10.1%-23%, observed 11.5%; and score greater than 40:
      predicted 23.1%-80%, observed 29.9%. For the EuroSCORE, findings were as follows:
      score 0%-2%: predicted mortality 1.1%, observed mortality 0.6%; score 3%-5%:
      predicted 2.1%, observed 3.0%; score 6%-8%: predicted 4.1%, observed 3.5%; score
      9-11: predicted 7.6%, observed 6.6.%; and score greater than 12: predicted 13.8%,
      observed 14.0%. There was good agreement between the observed and expected number
      of deaths, with both models. The area under the ROC curve was higher for the
      Bernstein-Parsonnet model (0.83, odds ratio [OR] 2.01, 95% confidence interval
      [CI] 1.75-2.31, p < 0.0001) than for the EuroSCORE (0.73, OR 1.05, 95% CI 1.04
      1.07, p < 0.001). CONCLUSIONS: The 2000 Bernstein-Parsonnet model is a simple,
      objective system for the estimation of hospital mortality in patients undergoing
      cardiac surgery, with slightly higher calibration and discrimination than the
      EuroSCORE additive model.

PMID- 16427847
TI  - Invited commentary.

PMID- 16427848
TI  - Acute renal failure after cardiac surgery: evaluation of the RIFLE
      classification.
AB  - BACKGROUND: Acute renal failure increases risk of death after cardiac surgery.
      However, the definition of acute renal failure is not standardized. The Acute
      Dialysis Quality Initiative Workgroup has outlined consensus criteria. The aim of
      the present study was to evaluate this determination of postoperative renal
      impairment in cardiac surgical patients, and its association with mortality.
      METHODS: The 813 consecutive patients undergoing cardiac surgery at Helsinki
      University Central Hospital were analyzed. According to the RIFLE classification
      (named by the severity of renal impairment: Risk, Injury, Failure, Loss, End
      stage kidney disease) patients were divided into three levels based on either
      plasma creatine level or urine output. The discrimination with death within 90
      days after surgery was determined. RESULTS: According to the RIFLE criteria,
      19.3% of patients had renal impairment after cardiac surgery. Patients in the
      more severe category, RIFLE-F (failure), had a 90-day mortality rate of 32.5%
      compared with 8.0% for those in RIFLE-R (risk) and 21.4% for RIFLE-I (injury)
      patients. The RIFLE classification discriminated 90-day mortality quite well
      (area under curve 0.824) compared with the change of plasma creatinine and the
      change of estimated gromerular filtration rate (areas under curve 0.849 and
      0.829, respectively). The results of the multivariate forward stepwise logistic
      regression analysis found that RIFLE classification was an independent risk
      factor for 90-day mortality (p < 0.0001), unlike change in glomerular filtration
      rate and change in plasma creatinine. CONCLUSIONS: We propose that the RIFLE
      classification is a valuable method to evaluate acute renal failure after cardiac
      surgery. The severity of RIFLE classification may be associated with increased 90
      day mortality rate.

PMID- 16427850
TI  - Invited commentary.

PMID- 16427849
TI  - Exploring the volume-outcome relationship for off-pump coronary artery bypass
      graft procedures.
AB  - BACKGROUND: The relationship between the surgical case volume and risk-adjusted
      clinical outcomes has been examined for different surgical specialties. The
      purpose of this study was to explore the relationship between the off-pump
      coronary artery bypass graft procedure volumes (OPCABG) with risk-adjusted
      outcomes within the Department of Veterans Affairs (VA) 44 cardiac surgery
      programs. METHODS: Based on VA Continuous Improvement in Cardiac Surgery Program
      data, the results of 5,076 OPCABG surgical procedures performed between October
      1998 and September 2003 were analyzed. Hierarchical logistic regression models
      evaluated the relationship between OPCABG procedure volume with risk-adjusted 30
      day operative mortality, perioperative morbidity, and 180-day mortality. Both a
      hospital's average OPCABG volume per 6-month period and the hospital's most
      recent 6-month OPCABG volume were examined. RESULTS: Hospital OPCABG average
      volume in a 6-month period ranged from 0.2 to 47.4 procedures; whereas the most
      recent 6-month OPCABG hospital volume ranged from 0 to 76 OPCABG per site. No
      relationship between the volume measures and the outcome variables was found.
      CONCLUSIONS: We did not find an association between OPCABG volume with short-term
      mortality, perioperative morbidity, or intermediate-term (180-day) mortality.

PMID- 16427851
TI  - Off-pump versus on-pump coronary artery bypass grafting in consecutive patients:
      decision-making algorithm and outcomes.
AB  - BACKGROUND: Debate continues between on-pump or off-pump approach for coronary
      artery bypass grafting (CABG). We used off-pump coronary artery bypass grafting
      (OPCAB) as a tool within a decision-making algorithm driven by the patient
      related factors of coronary anatomy and comorbidity. Our analysis presents this
      decision algorithm and describes outcomes using this approach. METHODS: From
      January 2000 to December 2003, 592 consecutive patients undergoing isolated CABG
      were assigned by one surgeon to a technique: on-pump CABG or OPCAB according to
      (1) anatomy and (2) predicted risk. Anatomic factors against OPCAB were target
      vessel size less than 1.25 mm, calcification, poor quality, intramyocardial
      location, and multiple stenoses. Given that OPCAB could be performed safely,
      patients in the moderate risk range, ie, those elderly with multiple
      comorbidities, were preferentially treated using OPCAB. RESULTS: The OPCAB group
      had higher predicted 30-day mortality compared with the on-pump CABG group,
      consistent with the protocol's intent. However, morbidity and mortality were
      similar between on-pump CABG and OPCAB. The OPCAB patients received the same
      number of internal mammary artery grafts but fewer distal grafts. Mortality and
      observed to expected ratios were favorable for both groups and below those The
      Society of Thoracic Surgeons' predicted for OPCAB. CONCLUSIONS: Matching surgical
      strategy to patient-related factors and needs resulted in excellent outcomes. Our
      data support the use of a protocol based on patient characteristics to drive the
      surgeon's choice between an on-pump CABG or OPCAB approach. As such, OPCAB can be
      viewed as a tool to be used by the surgeon developing a best practice in treating
      coronary artery disease.

PMID- 16427852
TI  - Isoprostanes and oxidative stress in off-pump and on-pump coronary bypass
      surgery.
AB  - BACKGROUND: Conventional on-pump coronary artery bypass grafting (CABG) is
      associated with a systemic inflammatory response and by an increased production
      of reactive oxygen species, whereas off-pump coronary artery bypass grafting
      (OPCAB) is thought to be accompanied by less oxidative stress. Urinary
      isoprostane iPF2alpha-III is a new marker reflecting oxidative stress; it has
      emerged as the most reliable marker of oxidative stress status in vivo. This
      study was designed to ascertain whether OPCAB compared with CABG represents a
      surgical strategy that avoids oxidative stress. To this end urinary isoprostanes
      and other established oxidative stress markers were measured during the first 24
      hours after CABG and OPCAB. METHODS: Fifty low-risk coronary patients were
      randomly assigned to CABG or OPCAB. Urinary isoprostane iPF2alpha-III levels,
      plasma levels of free malondialdehyde, and total antioxidant status were measured
      before, during, and up to 24 hours after surgery. RESULTS: In OPCAB iPF2alpha-III
      excretion remained unchanged throughout the study. As expected, in CABG iPF2alpha
      III levels significantly increased during surgery and returned at baseline 24
      hours later. Free malondialdehyde behaved similarly, with no change in OPCAB and
      sharp increases during CABG. Conversely, total antioxidant status showed a sharp
      drop during CABG, followed by a slow recovery, whereas a significantly lower drop
      occurred in OPCAB. CONCLUSIONS: In this randomized study in low-risk coronary
      patients, OPCAB revealed less perioperative oxidative stress, as reflected by
      lack of excretion of iPF2alpha-III in urine, by lack of increase of plasma free
      malondialdehyde, and by lower decreases in plasma total antioxidant status.

PMID- 16427853
TI  - How safe is it to train residents to perform off-pump coronary artery bypass
      surgery?
AB  - BACKGROUND: The technique of off-pump coronary artery bypass graft (OPCABG)
      surgery differs considerably from on-pump CABG. This study investigates the
      impact of surgical training on clinical outcome in patients undergoing OPCABG.
      METHODS: All 251 OPCABG cases performed by one service over an 18-month period
      were analyzed. The 83 operations (33%) performed by two trainees under
      supervision were compared with the 168 operations (67%) performed by an
      experienced consultant surgeon. Patient and disease characteristics,
      intraoperative and postoperative data, morbidity and mortality were analyzed
      using univariate and multivariate analysis. Data were extracted from a
      prospective database. RESULTS: Patients operated on by the consultant were more
      likely to have had unstable angina (p = 0.003, odds ratio [OR] = 3.5), impaired
      left ventricular function (ejection fraction < 0.3; p = 0.005, OR = 2.4), or
      previous cardiac surgery (p = 0.03). They were more likely to receive three or
      more grafts (p = 0.017, OR = 2.0). Operative mortality was 2.4% (consultant) and
      0% (trainees; p = 0.31). Postoperative morbidity, such as reoperation for
      bleeding (consultant 3% versus trainees 1.2%), stroke (0.6% versus 1.2%), and
      hemofiltration (3.6% versus 0%) was similar between the two patient groups. Stay
      in the intensive care unit was not significantly different in the two groups.
      CONCLUSIONS: In our experience, trainee surgeons are less likely to operate on
      patients with unstable angina or cardiac dysfunction. Operative morbidity and
      mortality are, however, similar in patients operated on by either an experienced
      consultant surgeon or trainees. We believe OPCABG can be taught safely to
      trainees under supervision.

PMID- 16427854
TI  - On-pump beating-heart coronary artery bypass grafting for acute myocardial
      infarction.
AB  - BACKGROUND: The early results of emergent coronary artery bypass grafting by
      conventional operative method for acute myocardial infarction are reported to be
      poor. The purpose of this study is to evaluate on-pump beating-heart coronary
      artery bypass grafting for acute myocardial infarction. METHODS: Thirty-one
      patients with acute myocardial infarction underwent emergent surgery between
      January 1998 and June 2004 at Nayoro City General Hospital. In 16 patients, on
      pump surgery was performed on the arrested heart, and in the other 15, on-pump
      surgery was performed on the beating heart. Early results were compared between
      the two groups. RESULTS: Preoperative and perioperative patient characteristics
      revealed no significant differences between the two groups. Although there was no
      statistically difference between the two groups, the early mortality rates of on
      pump arrested-heart coronary bypass grafting (31.3%) was higher than that of on
      pump beating-heart coronary bypass grafting (13.3%). Postoperatively, the
      creatine kinase myocardial band value for the on-pump beating-heart group was
      significantly lower than that for the on-pump arrested-heart group (221 +/- 200
      IU/L versus 666 +/- 540 IU/L, p = 0.008). The incidence of postoperative acute
      renal failure was significantly higher in the on-pump arrested-heart group than
      in the on-pump beating-heart group (p = 0.034). The durations of ventilator use
      and inotropic agent use were longer in the on-pump arrested-heart group than in
      the on-pump beating-heart group, though the differences were not statistically
      different (p = 0.152, p = 0.223). CONCLUSIONS: On-pump beating-heart coronary
      artery bypass grafting has the possibility to eliminate intraoperative global
      myocardial ischemia and to be an acceptable surgical option for acute myocardial
      infarction associated with lower postoperative mortality and morbidity.

PMID- 16427855
TI  - A simple score to assess mortality risk in patients waiting for coronary artery
      bypass grafting.
AB  - BACKGROUND: Independent risk factors for death in patients waiting for elective
      coronary artery bypass surgery have previously been identified. A prioritization
      where these factors are considered may potentially reduce waiting list mortality.
      A simple score based on the risk factors was constructed and validated. METHODS:
      A scoring system based on risk factors in 5,864 consecutive patients operated
      from 1995 to 1999 was constructed. The following factors were included in the
      score: unstable angina (3 points [p]), left main stenosis (2p), concomitant
      aortic valve disease (2p), operative risk (0-2p), left ventricular ejection
      fraction (0-2p), and male gender (1p). The score was retrospectively validated in
      5,167 new patients operated from 1999 to 2003. Based on the sum of risk score
      points, the patients were divided into three risk groups: low risk (0-2p),
      intermediate risk (3-5p) and high risk (> or = 6p). The risk groups were related
      to waiting list mortality and clinical priority (imperative, urgent, and
      routine). RESULTS: Median waiting time was 33 days. Forty-two patients (0.8%)
      died while waiting for surgery (5.2 deaths/100 waiting years). Of the patients,
      2,406 (47%) were low risk, 1,990 (38%) intermediate risk, and 771 (15%) high
      risk. Mortality incidence in the high-risk group was fivefold higher than in the
      intermediate group and 25-fold higher than in the low-risk group (32, 7, and 1.3
      deaths/100 waiting years, respectively, p < 0.001 between all groups). Twenty
      three percent of the patients in the high-risk group had not been given
      imperative clinical priority. CONCLUSIONS: The score system identifies patients
      with increased risk of death while waiting for coronary artery bypass grafting.
      The score may be used to facilitate and improve the prioritization process.

PMID- 16427856
TI  - Preoperative white blood cell count is independently associated with higher
      perioperative cardiac enzyme release and increased 1-year mortality after
      coronary artery bypass grafting.
AB  - BACKGROUND: Elevated preprocedural systemic markers of inflammation, including
      white blood cell count, have been associated with adverse clinical outcomes after
      percutaneous coronary intervention. The relationship between preoperative white
      blood cell count and clinical outcomes after coronary artery bypass grafting is
      less clear despite increasing evidence that neutrophils participate in
      reperfusion injury. We sought to determine the relationship between preoperative
      white blood cell count and in hospital major morbidity and 1-year survival after
      coronary artery bypass grafting. METHODS: We prospectively studied 3,024
      consecutive isolated coronary artery bypass graft procedures. Preoperative white
      blood cell count was determined by automated counter, perioperative cardiac
      enzyme release by the creatine kinase-myocardial band isoenzyme, and all-cause
      mortality over the first postoperative year taken from a national death registry.
      Multivariate logistic regression and Cox proportional hazards analyses were
      performed. RESULTS: Preoperative white blood cell count offered as a continuous
      variable and as five predetermined groups was independently associated with
      cardiac enzyme release three or more times the upper limit of the reference range
      (adjusted odds ratio = 1.5 per 10 x 10(9)/L increase, 95% confidence interval:
      1.2 to 2.0, p = 0.002) and higher 1-year mortality (adjusted hazard ratio = 1.6
      per 10 x 10(9)/L increase, 95% confidence interval: 1.2 to 2.1, p < 0.001).
      CONCLUSIONS: Higher preoperative white blood cell count is independently
      associated with higher perioperative myonecrosis and 1-year mortality after
      coronary artery bypass grafting.

PMID- 16427857
TI  - Invited commentary.

PMID- 16427858
TI  - Does coronary artery bypass graft surgery improve survival among patients with
      end-stage renal disease?
AB  - BACKGROUND: Cardiovascular disease remains the most frequent cause of death for
      patients with end-stage renal disease. To determine the long-term benefit of
      surgical revascularization in this high-risk population, we studied our patients
      with ESRD having coronary artery bypass graft surgery (CABG), comparing the
      results of off-pump to on-pump revascularization. As a baseline reference group,
      we used dialysis patients with a diagnosis of coronary artery disease who did not
      have surgical revascularization or percutaneous coronary interventions. The
      control group data set was obtained from the United States Renal Data System.
      METHODS: From January 1995 through July 2003, 158 patients with end-stage renal
      disease who were on hemodialysis (excluding those in cardiogenic shock, needing
      resuscitation, and with emergent or salvage status) underwent CABG. Fifty-nine
      patients (37.3%) had off-pump revascularization, and 99 patients (62.7%) had
      bypass grafting utilizing extracorporeal circulation. Preoperative risk factors
      and operative results were analyzed, and longitudinal survival data obtained.
      RESULTS: The mean follow-up time was 39.1 months (median, 33.1) for the on-pump
      patients and 18.3 months (median, 14.7) for off-pump. The total number of
      anastomoses per off-pump patient was 2.4 +/- 1.0, and with cardiopulmonary bypass
      (CPB), it was 3.3 +/- 0.9 (p < 0.001). Patients revascularized off-pump had an
      operative mortality rate of 1.7%, whereas patients grafted using CPB had an
      operative mortality of 17.2% (p = 0.003). The predicted risk of mortality for the
      off-pump group (9.3% +/- 7.4%) was not statistically different from the on-pump
      cohort (9.1% +/- 7.7%, p = not significant). Logistic regression analysis
      indicates that CPB use was an independent risk factor for early death (p = 0.01,
      odds ratio = 13.6, 95% confidence interval: 1.7 to 110). Long-term follow-up
      demonstrated that the patients revascularized using CPB had improved survival
      compared with the off-pump patients and the control population. CONCLUSIONS: Off
      pump CABG improves early mortality rate when compared with conventional
      revascularization. Despite a greater operative mortality, however, long-term
      survival is improved in the patients revascularized with CPB as compared with the
      off-pump cohort, suggesting possible advantages from a more complete
      revascularization in this population.

PMID- 16427860
TI  - Impact of diabetic retinopathy on cardiac outcome after coronary artery bypass
      graft surgery: prospective observational study.
AB  - BACKGROUND: Diabetic retinopathy is a manifestation of more severe diabetes. We
      sought to assess the impact of diabetic retinopathy on cardiac outcome of
      coronary artery bypass graft surgery (CABG). METHODS: We prospectively assessed
      the status of the retina of 74 consecutive diabetics who were referred for first
      time CABG, and compared cardiac outcome of CABG in diabetics with retinopathy
      with that in those without retinopathy. Cardiac events included recurrent angina
      or congestive heart failure that needed admission to hospital, myocardial
      infarction, repeat revascularization, and cardiac death. RESULTS: Twenty-six
      diabetics had retinopathy and 48 diabetics did not have retinopathy. Diabetics
      with retinopathy were likely to have higher hemoglobin A1c level (p = 0.048), and
      receive insulin treatment (p = 0.0065). In the 12 months of follow-up, 13 cardiac
      events occurred in diabetics with retinopathy and 7 in those without retinopathy
      (p = 0.0021). Among diabetics with retinopathy, heart failure or death due to
      heart failure accounted for 54% (7 of 13) of these cardiac events. Kaplan-Meier
      analysis showed significant difference in cardiac event-free survival between the
      two groups (p < 0.001). After adjustment for differences in patients'
      characteristics, diabetic retinopathy remained a predictor of cardiac event
      (adjusted relative risk = 4.2, 95% confidence interval, 1.5% to 11.9%; p =
      0.0067). CONCLUSIONS: After CABG, diabetics with retinopathy have a substantially
      increased risk of cardiac events, especially of congestive heart failure.

PMID- 16427859
TI  - Does bilateral internal thoracic artery grafting increase long-term survival of
      diabetic patients?
AB  - BACKGROUND: The purpose of the present study was to determine whether long-term
      survival in diabetic patients increased after bilateral internal thoracic artery
      (BITA) coronary bypass compared with matched patients with single internal
      thoracic artery (SITA) coronary bypass. METHODS: The propensity for BITA was
      determined using logistic regression analysis and each BITA patient was matched
      with one SITA patient. Between January 1992 and March 2002, 980 matched diabetic
      patients (490 BITA versus 490 SITA) underwent coronary artery bypass surgery.
      Long-term survival data were obtained from the National Death Index (mean follow
      up, 4.7 +/- 3.0 years). Groups were compared by Cox proportional hazard models
      and Kaplan-Meier survival plots. RESULTS: Multivariate Cox regression analysis
      determined that BITA grafting had no significant effect on long-term survival
      (hazard ratio 0.89, 95% confidence interval: 0.69 to 1.14, p = 0.343). There were
      no differences in 30-day mortality (3.9% for BITA versus 3.7%, p = 0.999) and
      major postoperative complications except for length of stay (11.4 days for BITA
      versus 12.7 days, p < 0.001). Five-year survival rate was 79.9% in the BITA group
      and 75.7% in the SITA group (p = 0.252). There was no difference in 5-year
      survival rate between matched patients younger than 60 or from 70 to 79 years
      old. However, BITA patients aged 60 to 69 years had better 5-year survival rates
      (84.1% versus 71.0%, p = 0.0196), whereas the opposite was observed in patients
      aged more than 79 years (5-year survival for BITA 43.1% versus 70.0%, p = 0.016).
      CONCLUSIONS: Bilateral internal thoracic artery grafting had no significant
      effect on long-term survival for diabetic patients, but it may increase long-term
      survival in patients aged 60 to 69 years, whereas SITA grafting may be beneficial
      for patients more than 79 years old.

PMID- 16427861
TI  - Cardioprotective effect of cold-blood cardioplegia enriched with N-acetylcysteine
      during coronary artery bypass grafting.
AB  - BACKGROUND: Cold-blood cardioplegia is a well-known method in coronary artery
      bypass graft surgery, and several authors have used various agents in the
      enrichment of cold-blood cardioplegia to decrease ischemia-reperfusion injury
      seen during surgery. N-acetylcysteine, which can increase glutathione levels, is
      one of the agents added to cardioplegic solutions to decrease myocardial injury.
      This study was planned to assess the efficiency of N-acetylcysteine-enriched cold
      blood cardioplegia on early reperfusion injury in patients with ischemic heart
      disease undergoing coronary artery bypass grafting, using measurements of cardiac
      troponin I and malondialdehyde release. METHODS: Thirty patients (11 women and 19
      men) with left ventricular ejection fraction greater than 0.40 scheduled for
      coronary artery bypass grafting were randomly divided into two groups. We used
      cold-blood cardioplegia enriched with N-acetylcysteine (50 mg per kilogram of
      body weight) in the first group and cold-blood cardioplegia alone in the second
      group. Hemodynamic variables and clinical properties of the patients were
      preoperatively and postoperatively evaluated. Enzyme releases were measured in
      the early hours after the operation. RESULTS: In the N-acetylcysteine-enriched
      group cardiac troponin I levels were lower than in the N-acetylcysteine-free
      group, and this difference was statistically significant. Cardiac troponin I
      levels increased in both groups in the 6th and 12th hours postoperatively, but
      there was a statistically significant difference between the two groups.
      Malondialdehyde levels were significantly higher in the N-acetylcysteine-free
      group after the 6th, 12th, 24th, and 48th hours postoperatively when compared
      with the N-acetylcysteine-enriched group. CONCLUSIONS: N-acetylcysteine
      supplemented cold-blood cardioplegia minimizes myocardial injury in the early
      hours after and during the cardiac surgery.

PMID- 16427862
TI  - Effect of aprotinin and recombinant variants on platelet protease-activated
      receptor 1 activation.
AB  - BACKGROUND: Thrombin generated during cardiopulmonary bypass activates the high
      affinity thrombin receptor, protease-activated receptor 1 (PAR1), causing
      platelet dysfunction and excessive bleeding. The serine protease inhibitor
      aprotinin protects platelets against thrombin-mediated PAR1 activation in vitro
      and in vivo. Here we have investigated three novel recombinant aprotinin variants
      with specific modifications to the active site lysine at amino acid position 15
      (arginine-15, arginine-15-alanine-17, and valine-15-leucine-17) for their effect
      on PAR1-mediated platelet aggregation in vitro. METHODS: Aggregation studies were
      carried out using washed human platelets (n = 9) or platelet rich plasma (n = 7)
      from healthy volunteers activated with 1 or 5 nM thrombin. Recombinant aprotinin
      variants were used at the molar equivalent to 50 KIU/mL of the parent compound.
      The PAR1-specific antagonist peptide, FLLRN, was used at 500 microM. RESULTS:
      Platelet aggregation at low concentrations of thrombin (1 nM) was mediated
      exclusively through PAR1, as shown by inhibition of aggregation in the presence
      of FLLRN. At 1 nM thrombin, the mean percentage +/- SD aggregation of washed
      platelets was 68.6% +/- 12.3%. This was suppressed by each aprotinin variant at
      the 50 KIU/mL equivalent dose: arginine-15 (23.0% +/- 17.5%, p < 0.001); arginine
      15-alanine-17 (33.3% +/- 22.9%, p < 0.01); aprotinin (37.5% +/- 19.4%, p < 0.05);
      valine-15-leucine-17 (50.0% +/- 16.1%, not significant)). At 5 nM thrombin, which
      activates both high (PAR1) and low-affinity (PAR4) thrombin receptors on
      platelets, FLLRN and aprotinin failed to block aggregation: this finding
      indicates that aprotinin selectively targeted PAR1. In platelet-rich plasma,
      aggregation at 1 nM thrombin was 77.1% +/- 10.0%, and this was inhibited in the
      following order: arginine-15 (30.1% +/- 9.6%, p < 0.001); arginine-15-alanine-17
      (52.3% +/- 9.7%, p > 0.001); aprotinin (55.9% +/- 6.2%, p > 0.001); valine-15
      leucine-17 (73.7% +/- 7.1%, not significant). CONCLUSIONS: Aprotinin variants
      differentially inhibit PAR1-mediated platelet aggregation. With more
      understanding of the mechanisms of action of aprotinin and its derivatives, safer
      and more efficacious aprotinin variants may become available for clinical use.

PMID- 16427863
TI  - Invited commentary.

PMID- 16427864
TI  - Cardiac output augmentation during hypoxemia improves cerebral metabolism after
      hypothermic cardiopulmonary bypass.
AB  - BACKGROUND: Hypothermic circulatory arrest (HCA) impairs cerebral oxygen delivery
      (CDO2) and cerebral oxygen consumption (CMRO2), which are further reduced by
      perioperative hypoxemia. This study investigates if continuous hypothermic low
      flow cardiopulmonary bypass (HLF) or intermittent hypothermic low-flow
      cardiopulmonary bypass (IHLF) can prevent reductions in CDO2 and CMRO2 during
      hypoxemia. METHODS: Eighteen neonatal piglets, cooled to 16 degrees to 18 degrees
      C with cardiopulmonary bypass (CPB), were randomly assigned into three groups:
      HCA, HLF (50 cc.kg(-1).min(-1)), or IHLF (1 minute of HLF for every 15 minutes of
      HCA). After 60 minutes of hypothermia, normothermic CPB (100 cc.kg(-1).min(-1))
      was established and cerebral perfusion data measured at hyperoxemia (PaO2 150 to
      250 mm Hg), hypoxemia (PaO2 50 to 60 mm Hg), and severe hypoxemia (PaO2 30 to 40
      mm Hg), and with increased CPB flow (200 cc.kg(-1).min(-1)) during severe
      hypoxemia. RESULTS: The CMRO2 (in mL O2.100 g(-1).min(-1)) was lower after HCA
      (2.5 +/- 0.3), compared with HLF (4.1 +/- 0.5, p = 0.02) and IHLF (6.2 +/- 0.8, p
      = 0.002). Within groups, the change from hyperoxemia to severe hypoxemia resulted
      in decreased CMRO2: HCA (1.3 +/- 0.2, p = 0.004), HLF (3.0 +/- 0.5, p = 0.01),
      and IHLF (2.9 +/- 0.5, p = 0.01). During severe hypoxemia, increasing CPB flow
      (from 100 cc.kg(-1).min(-1) to 200 cc.kg(-1).min(-1)) improved CMRO2: HCA (1.9 +/
      0.5, p = 0.05), HLF (4.2 +/- 0.5, p = 0.05), and IHLF (7.4 +/- 0.5, p = 0.04).
      CONCLUSIONS: Hypoxemia reduces CDO2 and CMRO2 despite the method of hypothermic
      CPB. Increased CPB flow during hypoxemia can restore both CDO2 and CMRO2 to
      values found with hyperoxemia and slower CPB flows. Augmenting cardiac output
      during periods of perioperative hypoxemia may prevent cerebral injury after
      exposure to hypothermic cardiopulmonary bypass.

PMID- 16427865
TI  - Hypercholesterolemia impairs the myocardial angiogenic response in a swine model
      of chronic ischemia: role of endostatin and oxidative stress.
AB  - BACKGROUND: Recent studies have shown that angiogenesis is regulated by a balance
      between activators and inhibitors. We investigated the effects of
      hypercholesterolemia on the functional angiogenic response and collateral
      formation induced by chronic myocardial ischemia and the expression of angiogenic
      mediators. METHODS: Twelve Yucatan miniswine, fed either a normal (NORM, n = 6)
      or high cholesterol (HCHO, n = 6) diet for 13 weeks, underwent ameroid
      constrictor placement around the circumflex artery. Three weeks later, myocardial
      perfusion was quantified using isotope-labeled microspheres. Seven weeks after
      ameroid placement, coronary microvascular responses and myocardial perfusion were
      assessed. Vascular density was evaluated by PECAM-1 (CD-31) staining, and
      vascular endothelial growth factor, endothelial nitric oxide synthase,
      endostatin, and angiostatin protein levels were determined. Myocardial protein
      oxidation was quantified. RESULTS: Coronary microvessels from HCHO pigs showed
      significant endothelial dysfunction. Baseline-adjusted myocardial flow at 7 weeks
      was significantly reduced in the HCHO animals (-0.002 +/- 0.06 versus +0.23 +/-
      0.09 mL/min/g, HCHO versus NORM, p = 0.04). Endostatin expression was
      significantly increased in the HCHO pigs (2.2-fold, p = 0.001 versus NORM). There
      was a mild reduction in myocardial vascular endothelial growth factor expression
      (-29% +/- 14%, p = 0.09) in HCHO animals, but no difference in expression of
      endothelial nitric oxide synthase and angiostatin. The HCHO animals demonstrated
      increased myocardial protein oxidation compared with the NORM group (+155% +/-
      21%, p = 0.03 versus NORM). CONCLUSIONS: Ischemia-induced angiogenesis is
      inhibited in hypercholesterolemic pigs with a concomitant increase in endostatin
      expression and oxidative stress. These findings suggest that under conditions of
      hypercholesterolemia, coronary collateral development may be regulated by
      endogenous angiogenesis inhibitors such as endostatin as well as reactive oxygen
      species.

PMID- 16427866
TI  - Invited commentary.

PMID- 16427867
TI  - Differential distribution of lipid microemboli after cardiac surgery.
AB  - BACKGROUND: Lipid microemboli found in shed blood during cardiac surgery have
      been shown to block capillaries of the brain postoperatively. In this study, the
      distribution of lipid microemboli in different regions of the brain and other
      organs was examined. A novel porcine model using radioactive lipid particles was
      used. METHODS: Ten animals (2 controls and 8 cases) were anesthetized and put on
      cardiopulmonary bypass. A shed-blood phantom was produced from arterial blood,
      saline, and tritium-labeled triolein. The phantom was infused into the
      cardiopulmonary bypass circuit. Tissue samples were taken postmortem from
      examined organs and prepared for scintillation counting. Levels of radioactivity
      were used as a measure of the uptake of lipid microemboli. RESULTS: High levels
      of radioactivity were found in kidney and spleen (5 to 10 times higher than in
      the other organs investigated). In the brain, radioactivity was found in all
      regions examined. The gray matter of cerebrum showed the highest level of the
      regions examined. CONCLUSIONS: This study shows that embolization of lipids is
      not a phenomenon restricted to the brain, but affected all the organs examined.
      The high levels found in the kidneys, and the relatively high levels in the gray
      matter of the cerebrum further legitimize the debate on the impact lipid
      microemboli has on postoperative kidney and cognitive dysfunction.

PMID- 16427868
TI  - Invited commentary.

PMID- 16427869
TI  - Prevention of postoperative pericardial adhesions with a novel regenerative
      collagen sheet.
AB  - BACKGROUND: Postoperative pericardial adhesions make a repeat sternotomy time
      consuming and dangerous. The purpose of this study was to evaluate the efficacy
      of a new collagen pericardial substitute for preventing postoperative pericardial
      adhesions. METHODS: Our absorbable substitute consists of three layers: a middle
      layer of aterocollagen between two layers of sodium hyaluronic acid and
      aterocollagen. In experiment 1 in this study, the patch, made of 9,000 filaments
      of aterocollagen fibers, (group 1; n = 5) was compared with a patch made of 6,000
      filaments (group 2; n = 7), an expanded polytetrafluoroethylene sheet (group 3; n
      = 6), and a control group (group 4; n = 4). Subsequently, in experiment 2, the
      patch was examined at 4 weeks (n = 5), 12 weeks (n = 5), and 24 weeks (n = 4)
      after the operation by light microscopy and scanning electron microscopy.
      RESULTS: The area of adhesion in group 1 was significantly less as compared with
      that in the other three groups, and the coronary vessels were clearly
      identifiable; on the other hand, all the animals in the control group showed
      moderate to severe adhesions, and the coronary vessels were completely obscured.
      In experiment 2, formation of a membranous tissue resembling the native
      pericardial membrane was observed in all animals, and the thickness of this
      membrane showed a marked increase by 24 weeks after the operation. Light
      microscopy and scanning electron microscopy also showed the formation of a
      mesothelium-like lining. CONCLUSIONS: The new absorbable and regenerative
      collagen patch seemed to be biocompatible, and its use was associated with
      minimal adhesion formation and preserved coronary anatomy.

PMID- 16427870
TI  - Celsior preserved cardiac mechanoenergetics better than popular solutions in
      canine hearts.
AB  - BACKGROUND: Better protective effects of Celsior on cardiac function than the
      other conventional solutions have been reported in acute experiments and in
      clinical trials for at-risk patients. However, no study has yet precisely
      elucidated how these preservation solutions affect cardiac mechanoenergetics.
      Therefore, we evaluated the effects of St. Thomas' Hospital solution No. 2,
      University of Wisconsin solution, and Celsior on left ventricular contractility
      (Emax: end-systolic pressure-volume ratio) and oxygen consumption. METHODS: We
      used 32 canine excised cross-circulated hearts. Twenty-three hearts served as
      donor hearts after hypothermic ischemia with one of the three solutions, and the
      remaining 9 served as controls. After arrest with each solution, the hearts were
      preserved for 4 hours at 4 degrees C. Then, we measured left ventricular
      pressure, volume, and oxygen consumption to obtain Emax and the relation between
      ventricular pressure-volume area (a measure of total mechanical energy) and
      oxygen consumption. We also evaluated the oxygen cost of Emax by changing Emax
      with calcium administration. RESULTS: Celsior did not significantly affect E(max)
      (6.3 +/- 2.4 in control versus 5.3 +/- 1.3 mm Hg.mL(-1).100 g with Celsior) nor
      the oxygen cost of Emax (1.2 +/- 0.6 versus 1.6 +/- 0.5 mL O2.mL.mm Hg(-1).beat(
      1).100 g(-2), respectively). In contrast, St. Thomas' Hospital and University of
      Wisconsin solutions significantly decreased Emax (4.5 +/- 1.1 and 3.5 +/- 0.9 mm
      Hg.mL(-1).100 g, respectively) and increased the oxygen cost of Emax (2.5 +/- 0.8
      and 2.4 +/- 0.9 mL O2.mL.mm Hg(-1).beat(-1).100 g(-2), respectively) compared
      with control and Celsior-preserved hearts. The slope and intercept of the oxygen
      consumption versus pressure-volume area relation showed no significant difference
      among the four groups. CONCLUSIONS: Celsior showed better protective effects on
      cardiac mechanoenergetics than St. Thomas' Hospital and University of Wisconsin
      solutions in the acute phase of heart transplantation.

PMID- 16427871
TI  - Physical activity patterns of children after neonatal arterial switch operation.
AB  - BACKGROUND: Physical inactivity is a major atherosclerosis risk factor. The
      exercise tolerance is usually excellent after neonatal arterial switch operation,
      but those patients in whom coronary anomalies remain the main late complication,
      risk developing atherosclerotic coronary disease owing to perceived physical
      activity restrictions. METHODS: We investigated physical activity patterns of 52
      unselected children 7 to 14 years after neonatal arterial switch operation for
      transposition of the great arteries by 24-hour continuous heart rate monitoring.
      The percentage of heart rate reserve was used to measure the amounts of
      activities. Comparisons were made with 35 children with repaired atrial or
      ventricular septal defect and with 127 age-matched healthy children. RESULTS:
      Children after arterial switch operation accumulated 167.3 +/- 70.6, 25.3 +/-
      12.9, and 15.7 +/- 11.3 minutes a day (mean +/- SD) of light, moderate, and
      vigorous physical activities, respectively. At the same activity levels, children
      with repaired septal defect accumulated 165.2 +/- 82.2, 26.2 +/- 11.7, and 16.2
      +/- 9.1 minutes a day, and their healthy peers 164.8 +/- 74.5, 31.8 +/- 13.9, and
      21.9 +/- 11.3 minutes a day. Both cardiac groups were significantly less active
      than the control group when considering moderate (p = 0.026) and vigorous
      activities (p = 0.006). Only 19% and 27% of the children after arterial switch
      operation engaged, respectively, in more than 30 minutes a day of moderate
      activity and 20 minutes a day of vigorous activity. CONCLUSIONS: Children after
      arterial switch operation, just like other cardiac children, do not meet the
      guidelines for physical activity. We should encourage regular physical activity
      to offset adult sedentary behavior and to prevent atherosclerotic cardiovascular
      disease in those patients whose long-term function of the coronary arteries
      remains a matter of concern.

PMID- 16427872
TI  - Intermediate results of the double-switch operations for atrioventricular
      discordance.
AB  - BACKGROUND: Since 1987, anatomic biventricular repair using the double-switch
      operations has been our principal choice for patients with atrioventricular
      discordance. These alternative procedures have the theoretical advantage of using
      the anatomic left ventricle to support the systemic circulation. METHODS: A total
      of 45 patients underwent the double-switch operation. Their ages ranged from 6
      months to 21 years. Associated malformations included pulmonary atresia in 27,
      pulmonary stenosis in 11, and Ebstein's malformation in 5. An atrial switch plus
      an arterial switch procedure was performed in 7, and an atrial switch plus a
      Rastelli-type ventriculoarterial switch procedure in 38. Follow-up ranged from 6
      months to 15 years. RESULTS: Early mortality was 8.9% (n = 4). In the latter half
      of the series (n = 23, since 1994), there was no early death. Six patients died
      late. Actuarial survival at 5 and 10 years was 83.6% and 77.6%, respectively. Six
      patients required conduit replacement, and 2 required revision of an intraatrial
      baffle for pulmonary venous channel obstruction and infection, respectively.
      Freedom from reoperation was 95.3% at 5 years and 76.2% at 10 years. Freedom from
      arrhythmia was 88.8% at 5 years and 78.4% at 10 years. The systemic ventricular
      ejection fraction was 0.568 +/- 0.103 at 1 year (n = 39), 0.555 +/- 0.105 at 5
      years (n = 17), and 0.539 +/- 0.098 at 10 years (n = 12). CONCLUSIONS: The
      surgical results of the double-switch operations have been improving.
      Intermediate follow-up suggests that these alternative procedures are a
      reasonable option for patients with atrioventricular discordance.

PMID- 16427873
TI  - Successful management of patients with pulmonary atresia with intact ventricular
      septum using a three tier grading system for right ventricular hypoplasia.
AB  - BACKGROUND: We sought to validate a simple grading scheme for right ventricular
      hypoplasia in determining suitability for a biventricular repair. METHODS: We
      reviewed the medical records for 106 patients with pulmonary atresia-intact
      ventricular septum (PA-IVS) treated between 1982 and 2001. Over this period,
      children were assigned to mild (> 2/3 normal size, 23.7% of patients), moderate
      (1/3 to 2/3, 41.2%), or severe (1/3, 35.1%) right ventricular hypoplasia, and
      this grouping, along with severity of coronary anomalies (45% right ventricle to
      coronary fistulae, 16% with right ventricle dependent coronary circulation
      [RVDCC]), triaged children to eventual single ventricle (severe) or two-ventricle
      (mild or moderate) repair. RESULTS: Actuarial 10-year survival was 86.3% with
      mortality predicted by severe hypoplasia (odds ratio [OR] 12.9, p < 0.001), RVDCC
      (OR 15.0, p < 0.001), and non-Caucasian race (OR 10.7, p < 0.001). Multivariate
      analysis with a Cox proportional hazards model confirmed only RVDCC (risk ratio
      [RR] 10.9, p = 0.0009} and non-Caucasian race (RR 6.9, p = 0.007) as significant.
      Although not an independent risk factor for survival, the degree of hypoplasia
      was the most important determinant for definitive repair. Severe hypoplasia
      virtually precluded two-ventricle repair (OR 33.1, p < 0.001 by chi2 analysis)
      and was the strongest risk factor for a one-ventricle system (OR 78.7, p <
      0.001). Actuarial survival after either repair was 91%, and no biventricular
      repair later converted to a Fontan system. CONCLUSIONS: Surgical management of
      patients based on this three tier grade for right ventricular hypoplasia results
      in excellent survival and correctly predicts patients destined for eventual
      Fontan and biventricular repair.

PMID- 16427874
TI  - Impact of the off-pump Fontan procedure on complement activation and cytokine
      generation.
AB  - BACKGROUND: To investigate whether the Fontan procedure in an off-pump fashion is
      less invasive in terms of the systemic inflammatory reaction. METHODS: Plasma
      levels of complement and cytokines were measured during and after the Fontan
      procedure in consecutive 38 patients. Of these, 16 underwent the extracardiac
      method without use of cardiopulmonary bypass (off-pump group), while the machine
      was used in the remaining 22 because of intracardiac maneuvers concomitantly
      needed (CPB group). RESULTS: There was no difference, between these two groups,
      in any value of plasma complement or cytokines after anesthetic induction.
      Immediately after commencement of the Fontan circulation, however, plasma
      concentration was significantly lower in the off-pump group for activated
      complement 3 (C3a), interleukin-6, interleukin-8, and polymorphonuclear elastase.
      The C3a value was also lower at 2 hours later in the off-pump group than in the
      CPB group. Furthermore, the values even stayed within the normal ranges, in the
      off-pump group, for tumor necrosis factor alpha (TNFalpha) and thrombomodulin. A
      pulmonary venous oxygen tension divided by an inspired oxygen tension
      (PpvO2/FiO2) ratio immediately after commencement of the Fontan circulation was
      528 +/- 93 mm Hg (410 to 580 mm Hg) in the off-pump group, and 258 +/- 167 mm Hg
      (86 to 540 mm Hg) in the CPB group (p = 0.01). Duration of drainage for fluid
      sequestration was shorter in the former group (6.3 +/- 0.7 days versus 13.9 +/-
      2.5 days, p = 0.02). CONCLUSIONS: Inflammatory reactions were attenuated when the
      Fontan procedure was employed in an off-pump fashion compared with the usual
      procedure on bypass.

PMID- 16427875
TI  - Tricuspid valve repair for Ebstein's anomaly in young children: a 30-year
      experience.
AB  - BACKGROUND: The purpose of this study was to examine early and late outcome of
      tricuspid valve repair for Ebstein's anomaly in young children. METHODS: Between
      October 1974 and November 2003, 52 children (25 boys) underwent tricuspid valve
      repair and annuloplasty for Ebstein's anomaly. Mean age was 7.1 +/- 3.9 years
      (range, 5 months to 12 years). Concomitant procedures included atrial septal
      defect closure (n = 46), division of accessory conduction pathways (n = 4),
      ventricular septal defect closure (n = 3), and other (n = 7). RESULTS: Early
      mortality was 5.8% (3 of 52 patients; no mortality since 1984, n = 31). Risk
      factors were age younger than 2.5 years (p = 0.03) and weight less than 10.7 kg
      (p = 0.03). Morbidity included transient atrial (n = 11) and ventricular
      arrhythmias (n = 5), and early reoperation in 3 patients. There was no need for a
      permanent pacemaker. Mean follow-up was 12.2 +/- 7.4 years (maximum, 24.3 years).
      Actuarial survival at 5, 10, and 15 years was 92.3% +/- 3.7%, 89.9% +/- 4.3%, and
      89.9% +/- 4.3%, respectively. Freedom from all reoperations at 5, 10, and 15
      years was 91.0% +/- 4.3%, 76.9% +/- 6.8%, and 61.4% +/- 8.8%, respectively.
      Moderate (grade II) or more tricuspid regurgitation on dismissal echocardiogram
      was the only risk factor for reoperation (p = 0.04). Tricuspid stenosis did not
      occur in any patient. At late follow-up, 89% of patients were in New York Heart
      Association class I or II. CONCLUSIONS: Ebstein's anomaly in young children can
      now be repaired with low mortality and good tricuspid valve durability. Tricuspid
      regurgitation at the completion of operation should be mild or less to minimize
      need for reoperation. Tricuspid valve repair and annuloplasty did not result in
      stenosis despite somatic growth. Most patients enjoy an excellent quality of
      life.

PMID- 16427876
TI  - Cardiac surgery in children with end-stage liver disease awaiting liver
      transplantation.
AB  - BACKGROUND: Cardiac repair for congenital heart disease in children awaiting
      liver transplantation presents unique therapeutic challenges and dilemmas. We
      tested the hypothesis that operations in these children requiring cardiopulmonary
      bypass (CPB) were not associated with prohibitive morbidity and mortality.
      METHODS: Over the last 10 years (1994-2004), five infants were identified in our
      database with end-stage liver disease and awaiting liver transplantation that
      required cardiac surgery. Primary end point for the study was mortality.
      Secondary end points included morbidity and time to liver transplantation. The
      new pediatric end-stage liver disease (PELD) model was used to score liver
      disease severity. RESULTS: Three boys and two girls with mean age of 8.6 months
      (range, 1.5-21 months) and mean PELD of 18.0 (range, 10-29) required CPB for
      repair. The only early mortality in the series occurred after cardiac arrest
      during creation of a central shunt. The child expired two days later despite
      extracorporeal membrane oxygenation support. The patient had important myocardial
      hypertrophy. All other patients survived and underwent successful liver
      transplantation. CONCLUSIONS: Children with significant congenital heart disease
      awaiting liver transplantation can undergo safe cardiac repair with judicious
      perioperative support thereby reducing the risks of subsequent liver
      transplantation.

PMID- 16427877
TI  - Temporary right heart support with percutaneous jugular access.
AB  - PURPOSE: Temporary right heart bypass has shown to improve hemodynamic stability
      and safety in beating heart revascularization. We sought to evaluate feasibility
      and safety of a right ventricular assist device percutaneously implanted in the
      right jugular vein. DESCRIPTION: The A-Med jugular coaxial cannula (A-Med Systems
      Inc, West Sacramento, CA) is designed for percutaneous implantation. Blood from
      the right heart is drained through the outer tube of this two-cannula device to a
      microcentrifugal pump and returned into the pulmonary artery through the inner
      tube. EVALUATION: In 10 patients scheduled for elective coronary bypass grafting
      without cardiopulmonary bypass, a total of 27 coronary anastomoses were performed
      with right heart support. Arterial pressure was significantly higher with right
      heart support when the heart was dislocated to access posterior and
      posterolateral anastomosis sites. Implantation through the right internal jugular
      vein was feasible without complications in all patients and facilitated the
      procedure. CONCLUSIONS: This initial study suggests safety and feasibility of
      temporary right heart support using percutaneous jugular access for posterior and
      posterolateral coronary bypass grafting.

PMID- 16427878
TI  - Portable coronary active perfusion system for off-pump coronary artery bypass
      grafting.
AB  - PURPOSE: The present study was performed to develop a new perfusion system for
      off-pump coronary artery bypass grafting and to examine whether even a simple
      coronary perfusion system can maintain adequate blood flow delivery during
      anastomosis. DESCRIPTION: The experiment was performed in two stages. In
      procedure 1, 3 pigs with left anterior descending artery occlusion were used to
      evaluate optimal perfusion flow rate and coronary artery internal pressure, and
      to evaluate the safety area of perfusion. In procedure 2, 6 pigs were used to
      validate the new portable coronary perfusion system. EVALUATION: The optimal
      blood flow in the portable coronary active perfusion system was less than
      approximately 40 mL/min. The small, easy to use pump system (ie, the portable
      coronary active perfusion system) may prevent hemodynamic deterioration and
      ventricular arrhythmia during coronary occlusion, resulting in better maintenance
      of left ventricular function. CONCLUSIONS: Even a simple pump system can achieve
      effective perfusion for safe anastomosis. Further studies are required to allow
      the clinical use of this system.

PMID- 16427879
TI  - Invited commentary.

PMID- 16427880
TI  - Pharyngo-colostomy with supraglottic partial laryngectomy in caustic
      oropharyngeal stricture.
AB  - We present two cases of chronic caustic stricture from the oropharynx to the
      entire esophagus combined with laryngeal stricture in which the piriform sinuses
      were stenosed. The restoration of digestive continuity was accomplished by end-to
      end pharyngo-colostomy at the level of the cricoid cartilage through the
      posterior mediastinal route. Supraglottic partial laryngectomy and pharyngoplasty
      were done simultaneously for the laryngeal and oropharyngeal stricture. The
      patients were able to swallow a soft blend diet to regular diet with negligible
      penetration.

PMID- 16427881
TI  - Human tracheal reconstruction with a composite radial forearm free flap and
      prosthesis.
AB  - Reconstruction of large tracheal defects has been largely unsuccessful. We report
      a novel single-stage tracheal reconstruction for a 6.5-cm long defect involving
      the anterior two thirds of the tracheal circumference in a patient with deeply
      infiltrative thyroid cancer into the tracheal lumen. The reconstruction was
      completed using a conduit composed of a radial forearm free flap for lining with
      a combined PolyMax mesh (Synthes, Paoli, PA) and Hemashield vascular graft
      (Boston Scientific, Natick, MA) for rigid support. At a 6-month follow-up the
      patient has normal swallowing and preoperative voice quality, and she maintains a
      patent, non-stented airway.

PMID- 16427882
TI  - Bilateral cervical lung hernia with T1 nerve compression.
AB  - Lung hernia is a rare condition. Approximately one third of cases occur in the
      cervical position. We report a case of bilateral cervical lung hernia associated
      with neuralgic pain that was repaired using bovine pericardium and biological
      glue.

PMID- 16427883
TI  - Direct cryosurgery for inoperable metastatic disease of the lung.
AB  - A 50-year-old woman presented with dyspnea associated with two isolated
      metastases in the right lung, which was 1 year after the resection of a primary
      pleomorphic fibrous histiocytoma from her left thigh. At a planned thoracotomy,
      the tumor was found to be advanced, contraindicating lobectomy. We aimed to
      completely destroy the tumor by applying cryosurgery.

PMID- 16427884
TI  - Cerebral air embolism during imaging of a sentinel lymphatic drainage in the
      respiratory tract.
AB  - We report a rare but notable case of cerebral air embolism complicating
      transthoracic intrapulmonary injection of an imaging agent used to locate
      sentinel lymph nodes. After a bolus injection of 2 mL of iopamidol into the
      peritumoral area with a 23-gauge needle, the patient complained of complete
      paralysis on his left side. Intraaortic gas was detected by computed tomography
      immediately after the injection. The patient recovered spontaneously without any
      additional complication. Surgeons should be aware of this rare but possible
      complication during sentinel lymph node assessment.

PMID- 16427885
TI  - Management of empyema cavity with the vacuum-assisted closure device.
AB  - Management of empyema after pulmonary resection remains a challenging problem.
      Along with mandatory drainage of the thoracic cavity and investigations to rule
      out bronchopleural fistula, a reliable method of thoracic cavity closure is
      needed. The open thoracic window and Eloesser flap techniques rarely represent
      definitive therapy. Muscle flap and thoracoplasty procedures may provide well
      vascularized tissue to close bronchopleural fistula and obliterate the empyema
      cavity, but they are quite complex and involve significant patient morbidity. We
      report a case of empyema without bronchopleural fistula after lobectomy in which
      the vacuum-assisted closure device was used to achieve complete wound healing
      after open drainage.

PMID- 16427886
TI  - Autoimmune myasthenia gravis after coronary artery bypass surgery.
AB  - Myasthenia gravis is the most common disorder of neuromuscular transmission and
      is a heterogeneous disorder that is generally autoimmune, which is caused by an
      auto-antibody to the nicotinic acetylcholine receptor. We present a rare case of
      myasthenia gravis that occurred 8 weeks after a coronary artery bypass grafting
      operation. A 64-year-old man with multivessel coronary artery disease underwent
      myocardial revascularization. Severe myasthenic symptoms began 8 weeks after the
      operation and emergent mechanical ventilation was needed because of myasthenic
      crises. The serum anti-acetylcholine receptor antibody level was high. The
      details of this unusual patient are discussed.

PMID- 16427887
TI  - Surgical repair of a chronic traumatic sternal fracture.
AB  - Chronic sternal fracture nonunion is usually reported after median sternotomy,
      but rarely after blunt chest trauma. Most traumatic fractures of the sternum are
      managed nonoperatively if they are asymptomatic and nondisplaced. Acute surgical
      therapy is indicated for debilitating chest pain usually associated with fracture
      displacement. We report a case of debilitating chest pain associated with a
      chronic sternal fracture. Our surgical technique is discussed and the literature
      is reviewed.

PMID- 16427888
TI  - Anastomotic obstruction after magnetic vascular coupling after minimally invasive
      direct coronary artery bypass grafting.
AB  - We report a 61-year-old man who required reoperation 8 months after minimally
      invasive direct coronary artery bypass grafting after magnetic vascular coupling
      due to a symptomatic subtotal obstruction at the anastomotic site. It was also
      determined that the patient had been noncompliant in following the prescribed
      postoperative antiplatelet therapy.

PMID- 16427889
TI  - Off-pump surgery for multiple coronary artery fistulas with aneurysm.
AB  - A 78-year-old woman presented with acute myocardial infarction, anterior wall,
      Killip III, with congestive heart failure. The finding of coronary angiographic
      examination was multiple congenital coronary artery fistulas with a huge
      aneurysm, with fistulas originating from both the right coronary artery and left
      anterior descending artery. The patient received surgery successfully without
      cardiopulmonary bypass. The finding of the pathologic examination revealed
      hyaline change in the aneurysmal vessel wall. In a two-year follow-up, the
      patient was found to be asymptomatic clinically with improved left ventricular
      function.

PMID- 16427890
TI  - Coronary artery revascularization after chest wall reconstruction with rectus
      abdominis myocutaneous flap.
AB  - The standard incision for a cardiac operation is a median sternotomy. In special
      situations, alternative approaches are needed. We report a 53-year-old woman who
      required coronary artery bypass grafting 10 days after chest wall reconstruction
      with a transverse rectus abdominis myocutaneous flap. We describe our technique,
      which allowed us to preserve the flap and resulted in good functional and
      aesthetic outcome.

PMID- 16427891
TI  - Rescue surgical embolectomy for fatal pulmonary embolism in patient with
      intracranial hemorrhage.
AB  - The incidence of pulmonary embolism is relatively high in stroke patients due to
      prolonged bed rest, paralysis of the lower extremities, and dehydration. We
      herein report three cases of pulmonary embolectomy for patients with intracranial
      hemorrhage. All patients had massive central pulmonary embolism and were in deep
      shock. The interval between the onset of intracranial bleeding and surgical
      embolectomy was 7 to 16 days. All patients underwent emergent pulmonary
      embolectomy using cardiopulmonary bypass and survived without any neurologic
      exacerbation. Surgical pulmonary embolectomy is a treatment of choice to save
      patients with massive pulmonary embolism after intracranial hemorrhage.

PMID- 16427892
TI  - Aortic valve replacement in a patient with thalassemia intermedia.
AB  - Pseudoxanthoma elasticum-like diffuse elastic tissue defects and
      hypercoagulability are two well-established features in beta-thalassemia, which
      play a key role in the development of a spectrum of collateral complications in
      these patients. We present here a middle-aged thalassemia intermedia patient with
      severe aortic stenosis caused by heavy calcification of the valve, a hallmark of
      pseudoxanthoma elasticum. The patient underwent a successful replacement of the
      valve, which is the first such operation ever reported in these patients.
      However, rapid thrombosis leaded to failure of the mechanical valve, despite
      proper antithrombotic therapy.

PMID- 16427893
TI  - Total anomalous pulmonary venous connection with intact interatrial septum.
AB  - The presence of an interatrial communication is considered an integral part of
      the diagnosis of total anomalous pulmonary venous connection and is believed to
      be essential for survival. We report a 9-month-old infant with obstructed
      supracardiac total anomalous pulmonary venous connection without an interatrial
      communication.

PMID- 16427894
TI  - Patent levoatrial cardinal vein without left heart hypoplasia.
AB  - We report a very rare case of a 38-year-old woman with an anomalous vein
      connecting the left atrium and superior vena cava. This vein originated from the
      roof of the left atrium and crossed the midline to join the normal right superior
      vena cava. Furthermore, there was no hypoplasia of the left heart, the atrial
      septum was intact, and all four pulmonary veins drained normally into the left
      atrium. Three-dimensional reconstructions and sagittal views on preoperative
      computed tomography clearly demonstrated a communication between the superior
      vena cava and the left atrium. The patient experienced increasing left-to-right
      shunt ratio and underwent successful surgical correction 3 years after the
      original diagnosis via ligation of the anomalous vein. This abnormal vein was
      considered to be a levoatrial cardinal vein. The embryology, physiology,
      diagnosis, and surgical repair of this rare lesion are discussed.

PMID- 16427895
TI  - Relief of compromised translocated right coronary artery blood flow by clockwise
      rotation of the heart in a Jatene procedure.
AB  - A 1.9-kg premature boy with transposition of the great arteries, ventricular
      septal defect, and patent ductus arteriosus received a Jatene procedure at 16
      days of age. His coronary artery pattern was type A. His arteries were harvested
      and translocated to appropriate holes in the sinus portion of his neoaorta.
      Partial obstruction due to torsion of the translocated right coronary artery was
      suspected, because the right ventricle turned pink in color to blue and
      bradycardia developed when cardiopulmonary bypass support was weaned. This was
      relieved by clockwise rotation of the heart, and the patient recovered well.
      Follow-up echocardiography 6 months later revealed good biventricular function.

PMID- 16427896
TI  - Right ventricular outflow tract stent as a bridge to surgery in a premature
      infant with tetralogy of Fallot.
AB  - Despite dramatic progress in neonatal cardiac surgery, prematurity and low birth
      weight remain risk factors for poor outcome. Attempts to delay intervention with
      supportive therapy have been shown to increase morbidity and mortality. We
      present a case of an 840 gram, 28-week gestation newborn with tetralogy of
      Fallot, in whom palliation was achieved with a right ventricular outflow tract
      stent. This management allowed subsequent successful complete repair.

PMID- 16427897
TI  - An alternative method to fenestrate the extracardiac fontan conduit in a patient
      with atrial situs inversus and levocardia.
AB  - This report describes the technique to fenestrate the extracardiac Fontan conduit
      without cardiopulmonary bypass in a patient with levocardia and atrial situs
      inversus.

PMID- 16427898
TI  - Three-dimensional demonstration of the collateral circulation to the artery of
      Adamkiewicz with 16-row multislice computed tomography.

PMID- 16427899
TI  - Multiple penetrating aortic ulcers.

PMID- 16427900
TI  - Treating gastric tube cancer with distal gastrectomy preserving the
      gastroepiploic artery.
AB  - Total resection of the gastric tube with lymphadenectomy is standard and reliable
      treatment for gastric tube cancer. However the risk associated with totally
      removing a gastric tube previously reconstructed through the posterior
      mediastinal route is significant, given the need to lyse a significant number of
      adhesions in order to reach the mediastinum. As a less invasive procedure, we
      used distal gastrectomy to treat superficial gastric tube cancer in 2 patients.
      The distal gastric tube was mobilized and resected with preservation of the right
      gastroepiploic artery, and the Roux-en-Y gastrojejunostomy was used for
      reconstruction. This procedure was curative with less surgical stress.

PMID- 16427901
TI  - Alternative bi-pectoral muscle flaps for postoperative sternotomy mediastinitis.
AB  - Suppuration, mediastinitis, and disruption of median sternotomy are all rare, but
      nevertheless severe complications. We propose a simple mobilization of the two
      pectoralis major muscles for use as flaps to fill the sternal defect without the
      need for humeral detachment or a second cutaneous incision. These will be
      supplied from both the thoracoacromial vessels and the perforating arteries of
      the nongrafted internal mammary artery (IMA). Our technique is quick and easy,
      giving excellent results. Furthermore, by maintaining the perforating branches,
      we also preserve the nongrafted IMA.

PMID- 16427902
TI  - Valve replacement after T-grafting: "beating heart surgery".
AB  - Patent internal thoracic and radial artery T-graft will adequately perfuse the
      heart during reoperation. Five of 1,023 patients with prior T-grafting had aortic
      (3) or mitral valve redo operations in which the heart was allowed to beat (after
      an initial dose of cardioplegia) during the operation without clamping the patent
      T-graft. Rapid resumption of cardiac function after one dose of cardioplegia and
      no intraoperative or postoperative evidence of myocardial infarction indicated
      adequacy of perfusion without apparent myocardial injury. This approach avoids
      injury to the T-graft from dissection and clamping, saves time, and simplifies
      the operation.

PMID- 16427903
TI  - Aneurysms after coarctation repair associated with hypoplastic aortic arch:
      surgical management through median sternotomy.
AB  - Aneurysm development after repair of aortic coarctation is not a rare
      complication, but it is highly related to hypoplasia of the transverse aortic
      arch. The optimal management of such cases is not clearly established. We propose
      a single-stage transmediastinal re-repair using moderate hypothermic
      cardiopulmonary bypass and antegrade selective cerebral perfusion.

PMID- 16427904
TI  - Thoracic endometriosis: current knowledge.
AB  - Thoracic endometriosis syndrome includes four well-recognized clinical entities,
      namely catamenial pneumothorax, catamenial hemothorax, catamenial hemoptysis and
      lung nodules, as well as some exceptional presentations. The etiological
      mechanisms of this syndrome are not well understood, and different theories have
      been proposed. Controversies exist about optimal management, as experience has
      been drawn from case reports and small clinical series. Surgery, hormonal
      treatments and combined approaches have all been proposed, with variable results
      in terms of short and long term outcome.

PMID- 16427905
TI  - Early postoperative anticoagulation after mechanical valve replacement: a
      systematic review.
AB  - The optimal approach to early postoperative anticoagulation after mechanical
      valve implantation remains controversial. This review article examines the
      pathogenesis of thrombus formation and the different strategies for early
      postoperative anticoagulation. The most commonly reported anticoagulation
      regimens had the after estimates of early postoperative thromboembolism and
      hemorrhage: oral anticoagulation alone (0.9%, 3.3%); oral anticoagulation with
      intravenous unfractionated heparin (1.1%, 7.2%); and oral anticoagulation with
      low molecular weight heparin (0.6%, 4.8%). Although intravenous heparin may be
      associated with a higher incidence of hemorrhage, a randomized trial is needed to
      provide the best evidence regarding early postoperative anticoagulation after
      mechanical valve implantation. Nearly four decades have passed since the first
      mechanical prosthetic valves were implanted. Frequent thromboembolic
      complications with the first mechanical valves led to recommendations of
      universal anticoagulation for these patients. Since then, several design changes
      and modifications have been made to improve the longevity, hemodynamics, and
      thrombogenicity of newer generation mechanical valves. With improved blood flow,
      less stasis, and less thrombogenic materials, lower rates of thromboembolism have
      been reported. Despite these advances however, thromboembolism and anticoagulant
      related bleeding continue to account for 75% of all complications after
      mechanical valve replacement. Occurring most commonly within six months after
      implantation, these complications can adversely affect mortality and quality of
      life. Furthermore, the threat of their occurrence creates a psychological burden
      for each patient with a mechanical valve. The need for life-long anticoagulation
      in patients with mechanical valves is not in dispute, and the perioperative
      management of anticoagulation during non-cardiac surgery has been reviewed
      extensively. However, the approach to early postoperative anticoagulation after
      mechanical valve implantation is still a matter of debate. The optimal intensity
      and timing of anticoagulation to prevent early thromboembolism after valve
      replacement surgery without postoperative bleeding complications is unknown.
      Hence, many anticoagulation protocols have been proposed, but a lack of consensus
      remains. The objectives of this study were (1) to reexamine the pathogenesis of
      thrombus formation and the need for anticoagulation; (2) to critically review the
      literature on early postoperative anticoagulation strategies; and (3) provide an
      estimate of the incidence of bleeding and thromboembolism for each approach to
      early postoperative anticoagulation.

PMID- 16427906
TI  - The Society of Thoracic Surgeons/American Association for Thoracic Surgery off
      pump training program.
AB  - BACKGROUND: Opportunities to acquire knowledge and skills in new technology are
      limited for cardiothoracic surgeons after completion of residency. In 2000 The
      Society of Thoracic Surgeons/American Association for Thoracic Surgery Joint
      Committee for New Technology Assessment accepted an educational grant from the
      Foundation for Advanced Medical Education to implement and test an instructional
      program for practicing cardiothoracic surgeons in off-pump coronary bypass
      surgery. METHODS: Twenty-four surgeons were selected for participation.
      Instruction was provided in three phases: (1) a preliminary video illustrating
      the techniques; (2) 2-day training sessions at two separate locations linked by
      videoconference; and (3) visits by trainees to observe preceptor surgeons at
      their institutions, followed by visits of preceptor surgeons to the institutions
      of the trainees. Evaluation of the program was made by review of trainee case
      lists in the year after completion of the program and by written surveys
      completed by trainees and preceptors. RESULTS: Seventeen surgeons completed all
      phases of the program. Most of them reported frequently utilizing off-pump bypass
      surgery in practice with good results. Two surgeons dropped out of the program
      before the first phase, and 5 surgeons did not complete all preceptor visits.
      Most survey respondents commented that the program met or exceeded their
      expectations. CONCLUSIONS: Some trainees were unable to complete proctor visits
      because of professional responsibilities at home or because of difficulty in
      advanced scheduling of procedures. More rigorous selection and stronger
      administrative controls might have reduced program dropouts. The instructional
      model worked extremely well for properly selected and motivated surgeons.

PMID- 16427907
TI  - Why should we repair ischemic mitral regurgitation?

PMID- 16427909
TI  - Technique of posterior mitral valve restoration.

PMID- 16427911
TI  - Clopidogrel-aspirin inhibit the thrombogenicity of St. Jude mechanical aortic
      prostheses.

PMID- 16427912
TI  - Flap-valve closure of ventricular septal defects.

PMID- 16427915
TI  - Does arch clamping increase stroke rates?

PMID- 16427916
TI  - Is re-dosing of vancomycin necessary?

PMID- 16427917
TI  - More biocompatibility in cardiopulmonary bypass for high-risk patients.

PMID- 16427920
TI  - ASGE/SAGES Working Group on Natural Orifice Translumenal Endoscopic Surgery White
      Paper October 2005.

PMID- 16427921
TI  - Routine vs. selective EUS-guided FNA approach for preoperative nodal staging of
      esophageal carcinoma.
AB  - BACKGROUND: EUS-guided FNA (EUS-FNA) is the most accurate method for lymph-node
      staging of esophageal carcinoma; however, it may not be necessary when EUS
      features are present that strongly suggest a benign or a malignant origin. AIMS:
      (1) To identify a combination of EUS criteria that have a sufficient sensitivity
      and specificity to preclude the need for EUS-FNA and (2) to assess the cost
      savings derived from a selective EUS-FNA approach. METHODS: A total of 144
      patients with esophageal carcinoma were prospectively evaluated with EUS.
      Accuracy of standard (hypoechoic, smooth border, round, or width > 5 mm) and
      modified (4 standard plus EUS identified celiac lymph nodes, >5 lymph nodes, or
      EUS T3/4 tumor) criteria were compared (receiver operating characteristic
      curves). Resource utilization of two diagnostic strategies, routine (all patients
      with lymph nodes) and selective EUS-FNA (FNA only in those patients in whom the
      number of EUS malignant criteria provides a sensitivity and a specificity <100%),
      were compared. RESULTS: Modified EUS criteria for lymph-node staging were more
      accurate than standard criteria (area under the curve 0.88 vs. 0.78,
      respectively). No criterion alone was predictive of malignancy; sensitivity and
      specificity reached 100% when a cutoff value of >1 and >6 modified criteria were
      used, respectively. The EUS-FNA selective approach may avoid performing FNA in 61
      patients (42%). CONCLUSIONS: Modified EUS lymph-node criteria are more accurate
      than standard criteria. A selective EUS-FNA approach reduced the cost by avoiding
      EUS-FNA in 42% of patients with esophageal carcinoma. These results require
      confirmation in future studies.

PMID- 16427922
TI  - Routine EUS-guided FNA for preoperative nodal staging in patients with esophageal
      carcinoma: is the juice worth the squeeze?

PMID- 16427923
TI  - EUS-guided FNA immediately after unrevealing transbronchial needle aspiration in
      the evaluation of mediastinal lymphadenopathy: a prospective study.
AB  - BACKGROUND: Transbronchial needle aspiration (TBNA) and EUS-guided FNA (EUS-FNA)
      are minimally invasive diagnostic approaches to mediastinal lymphadenopathy.
      Rapid on-site cytopathologic evaluation (ROSE) may facilitate the decision
      whether to proceed to a second procedure in the same session. The aim of this
      study was to determine the utility of TBNA with ROSE, combined with the option
      for immediate EUS-FNA in a single-session approach to mediastinal
      lymphadenopathy. METHODS: We prospectively recruited 20 patients (12 men; mean
      age 66.7 +/- 10.2 years) with mediastinal lymphadenopathy on CT who required
      cytopathologic evaluation. Bronchoscopy was first performed with TBNA and ROSE.
      If this was unrevealing, EUS-FNA was performed immediately afterward with ROSE.
      All procedures were performed with the patient under local anesthesia and
      sedation. RESULTS: TBNA specimens were deemed adequate on-site in 13 patients,
      and EUS-FNA was performed in the remaining 7 patients. TBNA with ROSE was falsely
      negative in one patient. The diagnostic yield for TBNA and EUS-FNA alone was 65%
      and 86%, respectively. This single-session approach provided a yield of 90%, with
      no complications. The final diagnoses were 12 non-small-cell lung cancer, two
      small-cell lung cancer, one metastatic adenocarcinoma, two sarcoidosis, one
      tuberculosis, one lymphoma, and one with no definitive diagnosis. CONCLUSIONS:
      Combining TBNA with the option for EUS-FNA immediately after unrevealing TBNA
      gave a yield approaching that of mediastinoscopy and, therefore, may reduce the
      need for invasive mediastinal sampling. This single-session endoscopic approach
      was safe, required only local anesthesia and sedation, was convenient, and
      obviated the need for patients to return for a second procedure.

PMID- 16427924
TI  - Targeting the mediastinum: one-stop shopping at all times?

PMID- 16427925
TI  - Endoscopic transmural drainage of pancreatic pseudocysts: results of a national
      and an international survey of ASGE members.
AB  - BACKGROUND: Pancreatic pseudocysts can be drained endoscopically via the
      transpapillary or the transmural routes. We sought to assess endoscopic methods
      of pseudocyst drainage. METHODS: A web-based survey was sent to American Society
      for Gastrointestinal Endoscopy (ASGE) members in the United States (U.S.) and
      internationally. RESULTS: Of the 3054 endoscopists to whom the survey was sent,
      266 (8.7%) replied; 198 performed pseudocyst drainage (103 [52%] ASGE members
      from the United States and 95 [48%] international members). The median of the
      total number of drainages per physician was 15 (range 1-364). The transgastric
      route was the most commonly used drainage route (65%). Transmural entry was
      performed by using a needle-knife in 53% of transmural drainages that were not
      EUS-guided. The number of stents placed ranged from 1 to 5 and these remained in
      place for 2 to 30 weeks. CT scan was used before drainage by 95% of all
      respondents. EUS imaging was used before drainage by 72 of 103 (70%) US
      endoscopists compared with 56 of 95 (59%) international endoscopists (p = 0.1).
      EUS-guided drainage was used by 56% of US endoscopists compared with 43%
      international endoscopists (p = 0.06). CONCLUSIONS: The most common site of
      transmural entry for drainage of pancreatic pseudocysts appears to be the
      transgastric route. Although CT is the most commonly used predrainage imaging
      modality, EUS is used before and during transmural drainage of pseudocysts in
      both the U.S. and abroad, particularly in academic medical centers. Use of EUS
      before or during drainage does not appear to be significantly different among
      endoscopists in the United States and internationally.

PMID- 16427926
TI  - Primary care physician attitudes toward endoscopic screening for GERD symptoms
      and unsedated esophagoscopy.
AB  - BACKGROUND: Current guidelines recommend consideration of screening patients with
      chronic GERD for Barrett's esophagus (BE). Unsedated esophagoscopy (UE) is a less
      costly alternative to standard EGD for identifying BE. The aim of this study was
      to determine the indications for EGD referral, the barriers to screening, and the
      interest in performing UE. METHODS: A one-page survey was mailed to a random
      sample of 500 family practitioners and 500 internists. This sample was obtained
      from the American Academy of Family Physicians and American Society of Internal
      Medicine (500 from each organization). RESULTS: The overall response rate was
      54%. The majority (78%) refer more than 50% of their GERD patients for EGD;
      however, 34% also refer more than 10% of their patients for barium studies.
      Primary care physicians cited alarm symptoms, refractory symptoms, and chronicity
      and severity of symptoms as the major indications for referral for EGD. Gender,
      age, obesity, and tobacco use were cited less frequently. Cost of endoscopy, poor
      patient acceptance, and lack of evidence were the most common reasons cited for
      not referring for EGD. A majority of respondents (62%) indicated that the
      availability of UE would increase referral for the procedure, and 52% would be
      willing to perform UE in their office. CONCLUSIONS: Severe, refractory, and
      chronic symptoms are the primary reasons for endoscopic referral from primary
      care physicians who manage patients with GERD. Other risk factors for BE, such as
      gender and age, do not appear to be important determinants for endoscopic
      referral. Further evaluation of UE as a mechanism to increase screening for BE in
      primary care patients is merited.

PMID- 16427927
TI  - ERCP findings in idiopathic pancreatitis: patients who are cystic fibrosis gene
      positive and negative.
AB  - BACKGROUND: Our series of patients with idiopathic pancreatitis (IP) found a
      cystic fibrosis (CF) gene abnormality in 19% compared with 3.5% in patients
      without pancreatitis. OBJECTIVE: The objective was to determine whether the CF
      gene predicts more severe ERP findings. DESIGN: This was a retrospective case
      control study. SETTING AND PATIENTS: From July 1998 to August 2004, CF gene
      analysis was performed in 819 patients with IP via Genzyme Genetics. The panel
      tests for 70 to 87 alleles and has a detection rate of more than 90% of the
      cases. Sixty-nine patients (8.4%) who had at least one CF gene positive mutation
      were the study cohort. A total of 218 patients with IP and negative CF gene
      mutation were randomly selected from our database to be in the control group.
      MAIN OUTCOME MEASUREMENTS: Pancreatograms were evaluated for chronic pancreatitis
      (CP) based on Cambridge criteria. The results of the gene analysis were not
      available at the time of pancreatogram interpretation. RESULTS: Among patients
      positive for the CF gene, 42 (61%) were women. The mean age at intervention was
      40 years (range 14-80 years), and 48 patients (70%) had cholecystectomy. Among
      patients who were negative for the CF gene, 147 (67%) were women. The mean age at
      intervention was 41 years (range 9-89 years), and 125 patients (57%) had
      cholecystectomy. Compared with controls, cases had higher incidence of CP (62%
      vs. 48%, p = 0.05), grade III CP (35% vs. 18%, p = 0.004), pseudocysts (12% vs.
      4%, p = 0.036) and pancreatic strictures (20% vs. 8%, p = 0.008). LIMITATIONS:
      The limitations of the study were (1) retrospective design and (2) the panel used
      tests only for 70 to 87 alleles (of approximately, 900 CF transmembrane
      conductance regulator genes known). CONCLUSIONS: The mean age at intervention in
      both groups was similar. CP, grade III CP, pseudocysts, and pancreatic strictures
      were more common among patients who were CF gene positive.

PMID- 16427928
TI  - Cystic fibrosis transmembrane regulator mutations and pancreatic disease: closing
      the gap between genotype and phenotype.

PMID- 16427929
TI  - Successful outcomes of a novel endoscopic treatment for GI tumors: endoscopic
      submucosal dissection with a mixture of high-molecular-weight hyaluronic acid,
      glycerin, and sugar.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has recently been developed
      for endoscopic treatment of GI tumors, which enables us to resect even large
      tumors en bloc. However, a considerable frequency of perforation has become
      another problem. The best way to prevent perforation is to create a sufficient
      submucosal fluid cushion (SFC). The aim of this study is to find out the
      feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a
      10% glycerin plus 5% fructose solution (Glyceol). METHODS: Sixty-seven
      consecutive GI tumors in 54 patients who met indication criteria of ESD were
      enrolled. The mixing ratios of Suvenyl and Glyceol were 1:3 for
      esophageal/colorectal tumors and stomach tumors with scar, and 1:7 for stomach
      tumors without scar. After creation of SFCs, mucosal incision around the tumors
      and submucosal dissection under the tumors were made by cutting devices. The
      clinical outcomes were investigated. RESULTS: Mean resected and tumor sizes were
      38.6 and 25.6 mm, respectively. Perforation occurred in one colon tumor with
      severe fibrosis (1.5%), which was managed by endoscopic clipping without salvage
      surgery. No blood transfusion was performed. In one stomach and in one rectal
      tumor (3%), endoscopic hemostasis was necessary because of postoperative
      bleeding. Overall endoscopic and histologic en bloc resection rates were 94%
      (63/67) and 78% (52/67), respectively, and there was no recurrence after follow
      up of 1 year. CONCLUSIONS: ESD when using a mixture of Suvenyl and Glyceol
      results in excellent outcomes, and this injection solution should be used for
      ESD.

PMID- 16427931
TI  - Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial
      results of a novel optical biopsy technique.
AB  - BACKGROUND: Biopsy and polypectomy frequently are performed for lesions that
      carry a low risk of malignant transformation in the colon. Elastic scattering
      spectroscopy (ESS) is a novel optical biopsy technique that can distinguish,
      almost instantaneously, between normal and abnormal tissue in vivo, without the
      need to remove tissue. We assessed the diagnostic potential of ESS in the colon
      to differentiate normal colonic mucosa, chronic colitis, hyperplastic polyps,
      adenomatous polyps (with dysplasia), and adenocarcinoma. METHODS: ESS spectra
      were obtained from 138 sites in 45 patients at colonoscopy. They were then
      compared with conventional biopsy specimens taken from the same site, including
      normal colonic mucosa, hyperplastic polyps, adenomatous polyps, chronic colitis,
      and colon cancer. Spectral analysis was carried out with a validated computerized
      model that used principal component analysis followed by linear discriminant
      analysis. Cross validation was carried out by using 60% of the data as a
      "training set" and the remaining 40% of the data as a "test set." RESULTS: A
      total of 483 spectra were analyzed (290 normal, 19 hyperplastic, 69 adenomatous
      polyps, 74 chronic colitis, and 31 colorectal cancer). The sensitivity and the
      specificity of differentiating adenomas from hyperplastic polyps was 84% and 84%,
      respectively; for cancer from adenomatous polyps, 80% and 75%, respectively; for
      colitis from normal tissue, 77% and 82%, respectively; and for dysplastic mucosa
      (from polyps) from colitis, 85% and 88%, respectively. CONCLUSIONS: ESS holds
      promise for differentiating colonic lesions with good accuracy and, therefore, is
      a potentially useful tool to make an instantaneous diagnosis during colonoscopy.
      It could prove a valuable aid for targeting biopsies in dysplasia surveillance in
      inflammatory bowel disease and for deciding which small polyps should be removed.

PMID- 16427930
TI  - Routine ileoscopy at colonoscopy: a prospective evaluation of learning curve and
      skill-keeping line.
AB  - BACKGROUND: Ileoscopy is the criterion standard for mucosal lesions of terminal
      ileum but is performed in 5% of colonoscopy activity, and the need for training
      is undefined. OBJECTIVE: To assess the learning curve and skill-keeping line of
      ileoscopy. DESIGN: Prospective randomized study. SETTING: Single GI endoscopy
      unit. PATIENTS: Adult outpatients referred for colonoscopy. INTERVENTIONS:
      Patient randomization to ileocolonoscopy by trainees and seniors. MAIN OUTCOME
      MEASUREMENTS: Ileoscopy skill was divided into the following: ileocecal valve
      (ICV) intubation (success rate, time) and ileal exploration (length, time).
      Consecutive blocks of 10 procedures were used to calculate the learning curve and
      the skill-keeping line. Variables considered to influence ICV intubation were the
      following: endoscopist experience, ICV morphology, patient age, gender, body mass
      index, diverticular disease, and preceding abdominal/pelvic surgery. RESULTS:
      Learning curve showed that competency in ICV intubation (80% success rate) and
      ileal exploration (16 cm) was achieved after 50 procedures. The skill-keeping
      line showed that ileoscopy was easy (97% success rate), fast (1 minute), and well
      accepted up to 45 cm of the ileum. Thin-lipped and volcanic ICV are the most
      difficult and easiest to intubate, respectively. Crohn's disease and adenomas of
      the proximal edge of ICV were diagnosed in 2.2%. CONCLUSIONS: Training in
      ileoscopy is recommended to achieve competency, and endoscopists should consider
      practicing ICV intubation to maintain and increase their skill. Ileoscopy can be
      difficult when the ICV is thin lipped or single bulged, and easy when it has a
      volcanic morphology.

PMID- 16427932
TI  - The effect of erythromycin on video capsule endoscopy intestinal-transit time.
AB  - BACKGROUND: Video capsule endoscopy (VCE) will fail to reach the cecum in 20% of
      patients within the 8-hour battery life. The use of prokinetics to improve VCE
      completion rates to the cecum remains unclear. The objective of this study was to
      determine whether erythromycin increases the completion rate of VCE to the cecum
      without adversely affecting image quality. METHODS: This was a prospective,
      randomized, single-blinded control trial at St. Vincent's Hospital, Melbourne,
      Australia. A total of 86 consecutive patients referred for VCE were considered
      for entry; 45 patients met the entry criteria. These 45 patients were
      prospectively randomized to no erythromycin (controls, n = 23) or 250 mg
      erythromycin (n = 22). Two gastroenterologists, who were unaware of which group
      the patients were randomized into, reported all VCEs. The number of VCEs that
      reached the cecum within the 8-hour study period, gastric emptying time (GET),
      and small-bowel transit time (SBTT) were calculated for each group. RESULTS:
      There was no significant difference in the number of VCEs that reached the cecum
      (32% failed to reach the cecum in the erythromycin group compared with 22% in the
      control group), GET, or SBTT between the two groups. Image quality was not
      adversely affected by the use of erythromycin. The dose and the preparation of
      erythromycin used in this study may have possibly had an effect on GET and SBTT.
      CONCLUSIONS: The use of erythromycin did not significantly increase the
      likelihood of the capsule reaching the cecum or affect the degree of visible
      peristalsis or the interpretation of capsule findings.

PMID- 16427934
TI  - To everything there is a season, and a time to every purpose...-Ecclesiastes iii,
      1.

PMID- 16427933
TI  - Endoscopic procedures and diagnoses are not influenced by seasonal variations.
AB  - BACKGROUND: The occurrences of various GI diseases are thought to be influenced
      by seasonal variations. The present study was done to test the hypothesis that
      seasonal variations in endoscopic diagnoses reflect underlying patterns in the
      performance of endoscopic procedures. METHODS: The Clinical Outcomes Research
      Initiative (CORI) uses a computerized endoscopic report generator to collect
      endoscopic data from 73 diverse practice sites throughout the United States. We
      used the CORI database to analyze the date-specific occurrence of EGD and
      colonoscopy, as well as the endoscopic diagnoses of gastric ulcer, duodenal
      ulcer, and colorectal cancer. Time trends are analyzed by autocorrelation and by
      linear and nonlinear regression. RESULTS: Between January 2000 and December 2003,
      the number of EGDs and colonoscopies increased 2.5- and 4.1-fold, respectively.
      The rate of duodenal ulcer fell from 21.2 (15.6-27.5) to 19.0 (15.8-22.8) per
      1000 EGDs. The rate of gastric ulcer fell from 42.6 (33.3-50.1) to 33.4 (29.5
      38.7) per 1000 EGDs. The rate of colorectal cancer fell from 109.9 (98.3-122.8)
      to 72.2 (67.4-77.2) per 1000 colonoscopies. The time trends of neither endoscopic
      procedures nor endoscopic diagnoses revealed any seasonal variation or other
      cyclic pattern. CONCLUSIONS: The performance of endoscopic procedures is
      unaffected by any seasonal variation.

PMID- 16427935
TI  - Can research in sports and other motor skills help improve endoscopy training?

PMID- 16427936
TI  - Consistency in patient and practice philosophy: an important consideration in
      seeking a position in private practice.

PMID- 16427938
TI  - Endoscopic papillectomy for adenomas of the major duodenal papilla (with video).

PMID- 16427937
TI  - Excellence in endoscopy: toward practical metrics.

PMID- 16427939
TI  - Endoscopic transgastric lymphadenectomy by using EUS for selection and guidance.
AB  - BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a reliable tool for
      tissue diagnosis of unexplained mediastinal or perigastric lymphadenopathy but
      may be ineffective in sampling a small malignant focus in it or removing an
      entire node. OBJECTIVE: To develop a new EUS-guided endoscopic-transgastric
      method to approach (sentinel) lymph nodes, including node marking and
      lymphadenectomy. DESIGN: Experimental study. SETTING: Animal experiments at an
      approved university college. SUBJECTS: Six pigs had a linear-array EUS
      examination 1 week after a transgastric procedure. All had reactive perigastric
      lymph nodes. INTERVENTIONS: Selected nodes were punctured with a 19-gauge EUS
      needle. A metal anchor with thread, loaded onto the needle, was placed across the
      lymph nodes to pull the node toward the stomach. After gastric-wall dissection
      with a needle knife at the point of emergence of the thread, the nodes were
      removed by pulling on the thread and the anchor. The gastric incision was closed
      with an endoscopic suturing system. MAIN OUTCOME AND MEASUREMENTS: Proof of the
      feasibility to endoscopically remove paragastric lymph nodes by an EUS-guided
      transgastric approach. RESULTS: In all pigs, lymph-node marking with an anchor
      and thread was possible. Traction exerted on these nodes showed that they could
      be pulled against the gastric wall for subsequent removal. In 2 of 6
      examinations, the entire sequence of the procedure, node tagging, gastric-wall
      incision, lymphadenectomy, and wall closure was performed. No serious
      complication occurred. LIMITATIONS: Animal study throughout, small numbers, no
      humans to date. CONCLUSIONS: Transgastric lymphadenectomy with EUS for node
      selection and capturing seems feasible.

PMID- 16427940
TI  - Transgastric anastomosis by using flexible endoscopy in a porcine model (with
      video).
AB  - BACKGROUND: Transgastric flexible endoscopic anastomosis might offer advantages
      over open and laparoscopic surgery, especially for bariatrics or patients with
      obstructive malignancy. OBJECTIVE: To develop methods for performing transgastric
      anastomosis. DESIGN/RESULTS: Twelve gastrojejunal anastomoses were formed in pigs
      weighing 27 kg to 38 kg (6 each in survival and nonsurvival groups) by using a
      per-oral double-channel gastroscope. The stomach was penetrated with a needle
      knife guidewire combination and bow-sphincterotome incision. The small intestine
      (SI) was grasped with a snare-over-forceps method and pulled into the stomach for
      suturing. Sutures were placed in pairs through the deep muscle of the stomach and
      small intestine to join the tissues securely. The SI was incised with a needle
      knife to open the anastomosis. Anastomoses were placed close to the
      cardioesophageal junction for bariatric purposes or in the antrum for pancreatic
      bypass. Survival studies in 6 pigs showed anastomosis patency at 7 to 10 days.
      CONCLUSION: Gastrojejunal anastomosis was accomplished via the transgastric route
      by using a new double-channel endoscopic method.

PMID- 16427941
TI  - Endoscopic resection with hypertonic saline-solution-epinephrine injection plus
      band ligation for large pedunculated or semipedunculated gastric polyp.
AB  - BACKGROUND: Endoscopic resection of pedunculated polyps with heads 1 cm or
      greater in diameter presents a risk of bleeding. To minimize this complication,
      we performed endoscopic resection with hypertonic saline-solution-epinephrine
      injection plus band ligation and evaluated its safety and effectiveness. METHODS:
      Seventeen patients with 20 pedunculated or semipedunculated polyps with heads 1
      cm or greater in diameter were treated with this technique. Conventional upper-GI
      endoscope, hypertonic saline-solution and epinephrine, sclerotherapy needle, and
      endoscopic band ligator device are needed for the procedure. OBSERVATIONS: All
      lesions were easily and safely resected. During this procedure, a band ligation
      chamber proved to be satisfactory for accurate recognition of a postpolypectomy
      ulcer under good visual control. No hemorrhage, perforation, or other
      complication occurred as a result of the use of this technique. The histologic
      resection margin was affected by nonneoplastic components in 6 of 20 lesions.
      Follow-up endoscopy 1 week later revealed a small, shallow ulcer without residual
      polyp in all lesions. CONCLUSIONS: This preliminary study suggests that
      endoscopic resection with hypertonic saline-solution-epinephrine injection plus
      band ligation is a simple and effective method for the prevention of polypectomy
      associated bleeding. Prospective trials, including randomized controlled studies,
      are required to evaluate the suitability of this modality for wide clinical use.

PMID- 16427942
TI  - Biliary drainage by using stents without a central lumen: a pilot study.
AB  - BACKGROUND: Despite several attempts to make the conventional tubular stents with
      a central lumen for flow less susceptible to a biofilm buildup and thereby
      prevent clogging, this goal has remained elusive. We hypothesized that the
      creation of pathways for fluid flow around the stent instead of through it would
      avoid this problem. The aim of our study was to report the development and the
      evaluation of a novel lumen-less stent. METHODS: By using a software computer
      modeling, a 10F "winged" stent was designed. A pilot feasibility study was
      performed by using a prototype of this stent for endoscopic biliary drainage in 5
      patients with malignant biliary obstruction. OBSERVATIONS: Modeling data revealed
      that the winged stent offers a larger surface area for flow, higher velocity of
      flow, and increased flow rates compared with the conventional tubular stent. In
      the clinical trial, there was a significant decrease of serum bilirubin after the
      placement of this stent (serum bilirubin before and 2 weeks after stent
      placement, 14.94 +/- 5.7 mg/dL vs. 2.86 +/- 1.4 [p < 0.004]), accompanied by
      radiologic evidence of decompression of the biliary system. CONCLUSIONS: We have
      shown that it is possible to provide adequate biliary drainage by using a stent
      without a lumen. Such a design may have potential clinical advantages over
      existing designs.

PMID- 16427943
TI  - Unusual gastrostomy-tube complication.

PMID- 16427945
TI  - Common bile duct stone caused by a phytobezoar.

PMID- 16427944
TI  - Mirizzi's syndrome: EUS appearance.

PMID- 16427946
TI  - Rupture of hydatid cyst into the biliary tract.

PMID- 16427947
TI  - Small-intestinal B-cell lymphoma manifesting as pneumobilia secondary to
      involvement of the major duodenal papilla.

PMID- 16427948
TI  - Nonsteroidal anti-inflammatory drug-associated ileal ulcers: an evaluation by
      double-balloon enteroscopy.

PMID- 16427949
TI  - Successful endoscopic retrieval of an impacted toothpick in the duodenum (with
      video).

PMID- 16427950
TI  - Duodenal metastasis from a primary angiosarcoma of the colon.

PMID- 16427951
TI  - Role of EUS and EUS-guided FNA in the diagnosis of symptomatic rectosigmoid
      endometriosis.
AB  - BACKGROUND: Rectosigmoid endometriosis is an underrecognized cause of GI symptoms
      in women. Pelvic magnetic resonance imaging and CT have a low sensitivity in
      making this diagnosis. The role of EUS and EUS-guided FNA (EUS-FNA) in the
      diagnosis of rectosigmoid endometriosis in symptomatic patients is not well
      studied. METHODS: A review of medical records identified 5 women who were
      diagnosed with rectosigmoid endometriosis by EUS and EUS-FNA over a period of 1
      year. OBSERVATIONS: Five women with nonspecific GI complaints underwent EUS
      examination of a rectosigmoid subepithelial mass found on colonoscopy. EUS
      revealed a hypoechoic lesion infiltrating the muscularis propria and the serosa
      of the rectal wall, and extending outside the rectal wall, findings consistent
      with rectosigmoid endometriosis. This diagnosis was confirmed by EUS-FNA,
      surgical exploration, and/or the patient's clinical course. CONCLUSIONS: EUS and
      EUS-FNA are noninvasive, sensitive techniques for the diagnosis of rectosigmoid
      endometriosis in symptomatic patients.

PMID- 16427952
TI  - Splenic vein thrombosis and Klebsiella pneumoniae septicemia after endoscopic
      gastric variceal obturation therapy with N-butyl-2-cyanoacrylate.

PMID- 16427953
TI  - Granular-cell tumor of the duodenum: a case report.

PMID- 16427954
TI  - Toxoplasma colitis in a patient with acquired immune deficiency syndrome.

PMID- 16427955
TI  - Colon cancer presenting as upper-GI bleeding.

PMID- 16427956
TI  - Salivary gland swelling developing after endoscopy: "anesthesia mumps".

PMID- 16427957
TI  - Inflammatory myofibroblastic tumor of the stomach: an unusual complication after
      gastrectomy.

PMID- 16427958
TI  - Recurrent Dieulafoy's ulcers in the stomach and colonic perforation caused by
      polyarteritis nodosa: report of a case.

PMID- 16427959
TI  - Ruptured duodenal varices after endoscopic ligation of esophageal varices: an
      autopsy case.

PMID- 16427960
TI  - Solitary rectal ulcer syndrome associated with ulcerative colitis.

PMID- 16427961
TI  - Handcrafted two-channel colonoscope for grasping forceps-assisted resection of
      giant pedunculated polyps.

PMID- 16427963
TI  - A prospective study of factors that determine cecal intubation time at
      colonoscopy.

PMID- 16427964
TI  - Inverted appendiceal orifice masquerading as a cecal polyp on virtual
      colonoscopy.

PMID- 16427965
TI  - Factors associated with breast cancer screening behaviours in a sample of Turkish
      women: a questionnaire survey.
AB  - The purpose of this descriptive correlational study was to identify breast self
      examination (BSE) and mammography rates and to examine variables related to the
      breast cancer screening behaviours in a sample of Turkish women. Data were
      collected from a convenience sample of 656 women, attending three health centres
      and two maternal and health centres, using an adapted version of Champion's
      revised Health Belief Model Scale. Results showed that 17% of the women reported
      performing BSE on a regular basis. Women, over the age of 40, 25% reported at
      least one mammography. Higher susceptibility to breast cancer, higher confidence
      for BSE, lower barriers to BSE, and having heard/read about breast cancer and BSE
      were significantly associated with performing BSE. Higher seriousness of breast
      cancer, higher benefits of having mammography, having heard/read about
      mammography, and having a gynaecologist as a regular physician were significantly
      associated with having mammography.

PMID- 16427966
TI  - Internet addiction in Korean adolescents and its relation to depression and
      suicidal ideation: a questionnaire survey.
AB  - This study examined the relationship of Internet addiction to depression and
      suicidal ideation in Korean adolescents. The participants were 1573 high-school
      students living in a city who completed the self-reported measures of the
      Internet Addiction Scale, the Korean version of the Diagnostic Interview Schedule
      for Children-Major Depression Disorder-Simple Questionnaire, and the Suicidal
      Ideation Questionnaire-Junior. A correlational survey design was employed. Among
      the samples, 1.6% was diagnosed as Internet addicts, while 38.0% was classified
      as possible Internet addicts. The prevalence of Internet addiction did not vary
      with gender. The levels of depression and suicide ideation were highest in the
      Internet-addicts group. Future studies should investigate the direct relationship
      between psychological health problems and Internet dependency.

PMID- 16427967
TI  - Validation of the Punjabi version of the Edinburgh postnatal depression scale
      (EPDS).
AB  - This study reports a project to validate a Punjabi translation of the Edinburgh
      postnatal depression scale (EPDS). The study involved three points of data
      collection. Bilingual (Punjabi and English speaking) new mothers completed the
      English and Punjabi EPDS on two separate occasions and underwent a diagnostic
      interview. At a threshold of 12.5 the Punjabi scale yielded a sensitivity of 71.4
      and specificity of 93.7. Analysis suggests criterion and conceptual equivalence
      between the two scales. A users' evaluation indicates that the tool was
      acceptable to the majority of mothers, however, the scale may be more applicable
      for mothers for whom Punjabi is their first language.

PMID- 16427969
TI  - Complications of body sculpture: prevention and treatment.
AB  - In many countries, lipoplasty is the most frequently performed aesthetic
      procedure. It has been promoted as a safe, easy-to-learn, outpatient procedure.
      Although plastic surgeons have developed safety measures to perform the
      technique, there are serious risks, including death at a rate of 1/5000
      procedures. Life-threatening complications include pulmonary embolism,
      hemorrhage, perforation, infection, lidocaine toxicity, epinephrine toxicity,
      third space fluid shifts, and fat embolism syndrome. Aesthetic complications
      include undercorrection (insufficient fat removal), overcorrection (excess fat
      removal), irregular fat removal with palpable and visible irregularities, edema,
      hematoma, seroma, local infection, cutaneous slough, hyperpigmentation,
      vasculopathies, and permanent color changes in the skin. In this article we
      present methods to prevent and, when possible, treat these complications.

PMID- 16427970
TI  - Liposuction: techniques and guidelines.
AB  - The apparent simplicity of liposuction and the ease with which it is performed,
      may lull the novice plastic surgeon into overlooking the evolutionary
      developments that have brought it to today's level of popularity in body
      contouring surgery. Patients who may benefit from liposuction range widely from
      the thin patient desiring contouring of localized areas of stubborn adiposity to
      the obese patient in whom diet has failed to control weight. One of the major
      drawbacks of liposuction is its ability to thin, but not tighten. Reliance upon
      skin retraction to affect a proper outcome will only lead to disappointment, and
      this patient may instead benefit from an excisional-type procedure. Careful
      patient selection, education, and proper administration of the technique as a
      primary or an adjunctive tool will help deliver the most desirable aesthetic
      result.

PMID- 16427971
TI  - Liposuction anesthesia techniques.
AB  - This article discusses intravenous sedation, the authors' anesthesia of choice
      when performing most esthetic body contour refinement procedures. This technique
      is comfortable, safe, contemporary, and beneficial to the patient and medical
      crew. The preanesthesia evaluation is emphasized as a safety and high-quality
      action to any anesthesia procedure. Alternative anesthesia techniques are also
      discussed, including their possible advantages, disadvantages, indications, and
      counterindications.

PMID- 16427972
TI  - Liposuction and tumescent surgery.
AB  - When guidelines for tumescent surgery are followed, treatment of patients with a
      broad range of concerns can be extremely effective. Whether its use is as a
      primary technique as in liposuction, or as an adjunct to another procedure such
      as reduction mammoplasty, the effects of reduced blood loss, pain control, and
      fluid management make it a powerful tool for the surgeon. Constant awareness of
      volumes infiltrated and aspirated, as well as the patient's clinical status, are
      critical in the safe delivery of tumescent surgery.

PMID- 16427973
TI  - Fat injection: a 20-year revision.
AB  - In the last 20 years, several different techniques of lipoinjection have been
      developed. Nevertheless, a standard procedure has not been adopted by all
      practitioners. There is no agreement as to the best way of processing the fat to
      ensure maximal take and viability of the graft. Other controversial issues
      include the ideal cannula for harvesting and reinjection, the presence of blood
      in the transplanted fat, trauma, air exposure, contamination of the graft,
      durability, and fat cell survival. Newly emerging approaches to fat tissue
      engineering with the use of cultured autologous preadipocytes may improve the
      technique of fat injection and transplant.

PMID- 16427974
TI  - Adipose tissue: stem cells and beyond.
AB  - This article highlights potential uses for harvested fat and describes the
      current state of the art regarding adipose stem cells.

PMID- 16427975
TI  - Subdermal liposuction: long-term experience.
AB  - This article discusses the technique of subdermal liposuction treating
      superficial subdermal fat. Advantages include the treatment of small adiposities,
      removal to favor skin accommodation, improvement of the cullulitic aspect of
      skin, and more progressive suction with better control of the evolution of the
      procedure.

PMID- 16427976
TI  - Sequential (serial) suction.
AB  - As the popularity of liposuction continues to increase, so have the variety of
      methods available to perform the procedure. One factor that remains the same
      regardless of how liposuction is performed is that there will always be a limit
      to how much fat can be removed in a single sitting. When amounts to be removed
      exceed safe quantities, serial suction offers a safe and effective approach to
      achieve the desired result.

PMID- 16427977
TI  - Abdominoplasty combined with lipoplasty without panniculus undermining:
      abdominolipoplasty--a safe technique.
AB  - This article discusses the author's technique of abdominoplasty that combines the
      excision of excess skin with lipoplasty without panniculus undermining and
      resection.

PMID- 16427978
TI  - Power-assisted liposuction.
AB  - This article describes vibroliposuction, a mechanical technique using compressed
      air to perform liposculpture.

PMID- 16427979
TI  - Liposuction and VASER.
AB  - VASER is a fat pretreatment device based on the emission of pulsed or continuous
      ultrasound energy to emulsify fat before its aspiration by means of suction
      assisted lipoplasty or power-assisted lipoplasty. If compared with previous
      generation UAL machines, it carries important technologic advances that focus on
      the safety and efficiency of the process. VASER is the result of improvements in
      surgical instrumentation and technique, proper use of wetting solutions, and
      knowledge about the best use of ultrasound for fat fragmentation. With its
      thinner cannulas and decreased use of ultrasonic energy, it allows greater
      emulsification of fat, creates more tunnels, diminishes the operative time,
      preserves vessels and nerves, and causes less pain and hematomas.

PMID- 16427980
TI  - Low-level laser-assisted liposuction: the Neira 4 L technique.
AB  - Low-level laser-assisted liposuction (LLLL), known as the Neira 4 L technique, is
      an excellent adjuvant tool for the surgeon practicing liposculpture. A low-level
      laser is used to create a transitory pore in the cell membrane of the adipocyte
      to move fat from inside the cell to the interstitial space outside without
      killing the cell. LLLL has been performed successfully in in-vitro and human
      adipose tissue cultures. It protects the patient from the surgical trauma of
      liposuction by protecting and preparing tissues for the surgical trauma;
      modulating the inflammatory response to prevent short and long-term side effects
      of surgery; and improving the quality and quantity of the healing process by
      accelerating recovery time, modulating secondary cicatrization, and preventing
      postoperative neuralgias.

PMID- 16427981
TI  - Complications of liposuction.
AB  - This article discusses the complications of liposuction and is divided into two
      parts. The first part discusses surgical and systemic complications. Since
      liposuction is surgery, it has the same complications as any surgery, but because
      of the minimalization of the procedure done by the author since he invented it in
      1977, the complications were and are still minimal in the traditional way. Others
      have tried to maximalize the procedure and so, almost immediately after, appear a
      maximalization of complications and new severe complications. The second part
      discusses sequelae or undesirable results, which are numerous and complex. To
      really understand these sequelae, the second part is divided into four sections:
      description of sequelae, how and why do they appear, how to try to avoid them,
      and how to try to treat them.

PMID- 16427982
TI  - Orthopoxvirus infection transmitted by a domestic cat.
AB  - The variola virus was declared eradicated by the World Health Organization in
      1980 but human infections by cowpox virus, another member of the genus
      Orthopoxvirus, are still observed, mainly in European countries. We report a
      woman who presented with two umbilicated vesicles surrounded by an indurated
      erythematous edema within cat scratch injuries on her thigh. The diagnosis of an
      Orthopoxvirus infection was based on the visualization of characteristic virus
      particles by electron microscopy and the detection of the A27L gene (14-kd fusion
      protein gene) of the genus Orthopoxvirus by polymerase chain reaction from a
      lesional skin biopsy specimen. Differential diagnoses of cat scratch disease,
      pustula maligna, and bullous impetigo were excluded by microbiologic
      investigation of the biopsy specimen. Both lesions scarred after 6 weeks of a
      continuous local antiseptic treatment.

PMID- 16427983
TI  - Tinea profunda cysticum caused by Trichophyton rubrum.
AB  - A 57-year-old Japanese woman developed multiple subcutaneous cysts located on the
      pubic region, thighs, back, and buttocks. She had been treated with systemic
      prednisolone and azathioprine for 3 years because of autoimmune hepatitis.
      Histologic examination revealed that the lesions were pseudocysts with numerous
      spores and hyphae. Trichophyton rubrum was identified in culture from the content
      of several examined cysts. The serum beta-D-glucan level was high (313 pg/mL),
      and a computed tomographic scan of the chest cavity showed infective embolism in
      the lung. To our best knowledge, this is the first reported case of multiple
      cystic tinea profunda, presumably with systemic dermatophyte infection. Systemic
      T-cell immunosuppression, as represented by a relatively low percentage of memory
      T cells and negative delayed-type hypersensitivity tests, is considered to cause
      this rare manifestation of dermatophytosis.

PMID- 16427984
TI  - Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with
      human herpesvirus 6 infection.
AB  - Drug hypersensitivity syndrome (DHS) is an idiosyncratic and life-threatening
      adverse drug reaction characterized by skin rash and multiorgan involvement. In
      rare cases, fulminant type1 diabetes mellitus (DM) may develop after DHS. Among
      proposed pathogenesis, human herpesvirus 6 (HHV-6) infections may play a role in
      the development of DHS. We report a case of DHS associated with HHV-6
      reactivation, complicated with a rare sequela of irreversible fulminant type 1
      DM. No diabetes-related autoantibodies were detected. Early detection and
      intervention for this serious complication should be given in patients with DHS.
      Fulminant type1 DM associated with DHS is reviewed. The role of HHV-6 in DHS
      associated with fulminant type 1 DM is also discussed.

PMID- 16427985
TI  - Severe erythema multiforme responding to interferon alfa.
AB  - Erythema multiforme (EM) is a targetoid eruption with interface pathology often
      triggered by a hypersensitivity response to a variety of infections, most
      commonly herpes simplex virus. Hepatitis C virus is rarely associated with EM. We
      present a 37-year-old man with an 8-year history of severe EM unresponsive to
      valacyclovir, acitretin, and cyclosporin, and marginally responsive to high-dose
      prednisone. The eruption had cleared 6 years previously during treatment with
      interferon for his concurrent hepatitis C virus. Although his viral titer was
      undetectable, we initiated therapy with interferon and ribavirin. The patient
      responded dramatically within 2 months and remained clear of EM after 1 year of
      continued interferon therapy. This is the third case reported in the world
      literature documenting a response of EM to interferon, and the first case in
      which hepatitis C virus was undetectable in serum prior to interferon therapy.

PMID- 16427986
TI  - Congenital leukemia cutis with subsequent development of leukemia.
AB  - We describe a newborn infant who was born with a purpuric rash and subcutaneous
      nodules. Skin biopsies demonstrated acute myeloid leukemia. Cytogenetic studies
      revealed an 11q23 rearrangement. Initial bone marrow and cerebrospinal fluid
      examination did not demonstrate medullary or meningeal disease. Chemotherapy was
      initiated on the basis of the abnormal cytogenetic findings in the skin biopsy.
      Intensive chemotherapy was, given but the infant's leukemia progressed. The
      patient died of refractory leukemia and secondary fungal disease. This case
      report supports the observation that leukemia cutis with an 11q23 rearrangement
      should be treated aggressively.

PMID- 16427987
TI  - Generalized pustular psoriasis of pregnancy treated with narrowband UVB and
      topical steroids.
AB  - A 19-year-old primigravida with a long history of plaque psoriasis presented
      during the second trimester with exacerbation of the disease. Examination
      revealed widespread psoriatic plaques with peripheral pustules. She was diagnosed
      with generalized pustular psoriasis of pregnancy. Histology of lesional skin was
      consistent with pustular psoriasis. Topical corticosteroids under occlusion
      resulted in only partial improvement. Hence, narrowband ultraviolet B
      phototherapy was added at 27 weeks gestation, which resulted in clinical and
      symptomatic improvement. This is the first case report of generalized pustular
      psoriasis of pregnancy treated successfully with narrowband ultraviolet B
      phototherapy.

PMID- 16427988
TI  - Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic
      involvement in a patient with respiratory failure.
AB  - Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a
      disorder occurring exclusively in patients with renal disease. Until recently, it
      has been considered a fibrosing disorder essentially confined to the skin and
      underlying superficial soft tissue. Recent reports, however, have described
      patients with involvement of other organ systems, suggesting that this disorder
      is actually a systemic disease with preferential cutaneous manifestations. We
      describe a patient with end-stage renal disease with diagnosed NFD/NSF who
      subsequently developed respiratory failure leading to his death. Autopsy findings
      showed NFD/NSF involving the skin of all extremities, as well as diffuse
      diaphragm involvement.

PMID- 16427990
TI  - Annular lipoatrophy of the ankles.
AB  - Lipoatrophic panniculitis likely represents a group of disorders characterized by
      an inflammatory panniculitis followed by lipoatrophy. It occurs locally in a
      variety of settings and has been reported in the literature under various terms,
      including annular atrophic connective tissue panniculitis of the ankles, annular
      and semicircular lipoatrophy, abdominal lipoatrophy, and connective tissue
      panniculitis. Herein, a case of annular lipoatrophy of the ankles is described in
      a 6-year-old girl with autoimmune thyroid disease. Histologically, a mixed
      lobular panniculitis with lipophages was present. This pattern resembles that
      seen in lipoatrophic panniculitis. After a single, acute episode of an
      inflammatory process with subsequent lipoatrophy, her skin lesions have
      stabilized for 2 years requiring no treatment.

PMID- 16427989
TI  - Hereditary woolly hair and keratosis pilaris.
AB  - We describe a family with woolly hair and ulerythema ophryogenes spanning four
      generations. Both woolly hair and ulerythema ophryogenes have been associated
      with Noonan syndrome and cardiofaciocutaneous syndrome (CFC), two disorders with
      considerable phenotypic overlap. This family did not exhibit any of the other
      findings characteristic of either Noonan syndrome or CFC, similar to a previously
      described pedigree with hereditary woolly hair. Woolly hair elicits a broad
      differential diagnosis, including woolly hair nevus and several genodermatoses.
      Our report reviews the evaluation of woolly hair and discusses the conditions
      associated with this physical finding.

PMID- 16427991
TI  - Scarring autoimmune bullous disease in a Ugandan patient with autoantibodies to
      BP180, BP230, and laminin 5.
AB  - We report on a 24-year-old, male Ugandan patient with a 2-week history of itchy
      papules, vesicles, erosions, and crusts distributed on the entire body,
      accompanied by minor erosions on the palate, tongue, and lower lip. Conjunctivae
      and genital mucosa were not involved. Circulating IgG and IgA autoantibodies were
      found against recombinant full-length BP180, BP180 4575, and the C-terminus of
      BP230. In addition, IgG reactivity was observed against the 16th noncollagenous
      region of the BP180 ectodomain, the cell-derived soluble ectodomain of BP180
      (linear IgA disease antigen 1), and the alpha3 and gamma2 chains of laminin 5. No
      reactivity was detected with type VII collagen, alpha6beta4 integrin, and the
      p200 protein. Oral prednisolone and dapsone led to clearance of lesions that
      mostly healed with scarring and milia formation. Here, we describe a scarring
      mucocutaneous variant of an autoimmune blistering skin disorder that extends the
      current clinical and immunopathologic spectrum of this group of diseases.

PMID- 16427992
TI  - Familial nevus sebaceus in dizygotic male twins.

PMID- 16427993
TI  - Actinic lichen nitidus in 3 African American patients.

PMID- 16427994
TI  - Primary cutaneous meningioma in association with a sinus pericranii.

PMID- 16427995
TI  - Bullous hemorrhagic dermatosis occurring at sites distant from subcutaneous
      injections of heparin: three cases.
AB  - Cutaneous side effects from heparin administration are rare and usually located
      at injection sites. We report 3 cases of intraepidermal hemorrhagic blisters
      occurring distant from sites of subcutaneous injections of heparin. A causative
      link is suggested by a temporal relationship between heparin introduction and
      onset of disease as well as exclusion of other causes, but the mechanism remains
      unknown.

PMID- 16427996
TI  - Paclitaxel for progressive basal cell carcinoma.

PMID- 16427997
TI  - Vulvar melanoma in a 10-year-old girl in association with lichen sclerosus.

PMID- 16427998
TI  - Multiple apocrine hidrocystoma showing plane pigmented macules.

PMID- 16427999
TI  - Penile condylomata? Traumatic neuromas!

PMID- 16428000
TI  - Psoriasis localized exclusively to peristomal skin.

PMID- 16428002
TI  - Dermatitis herpetiformis associated with administration of a gonadotropin
      releasing hormone analog.

PMID- 16428001
TI  - Disseminated superficial porokeratosis in a patient with cholangiocarcinoma.

PMID- 16428003
TI  - Syphilitic nodules on the tongue.

PMID- 16428004
TI  - Pseudoxanthoma elasticum and polymyositis in a child.

PMID- 16428005
TI  - Pustular leukemoid reaction in a neonate with Down syndrome.

PMID- 16428006
TI  - Cartilage hair hypoplasia and multiple basal cell carcinomas.
AB  - Cartilage hair hypoplasia (CHH) is an autosomal recessively inherited syndrome
      characterized by short stature, sparse hair, and immunodeficiency. An increased
      incidence of malignancy has been reported in this condition, but basal cell
      carcinoma and CHH has not previously been reported in the dermatology literature.
      We report the case of a 25-year-old woman with CHH and multiple basal cell
      carcinomas. A causal relationship is conceivable and, therefore, for patients
      with CHH, dermatologists should be aware of a possible increased risk of basal
      cell carcinomas.

PMID- 16428007
TI  - Simultaneous analyses of cocaine, cocaethylene, and their possible metabolic and
      pyrolytic products.
AB  - A method was developed for simultaneously analyzing cocaine (COC),
      benzoylecgonine (BZE), norbenzoylecgonine (BNE), norcocaine (NCOC), ecgonine
      (ECG), ecgonine methyl ester (EME), m-hydroxybenzoylecgonine (HBZE),
      anhydroecgonine methyl ester (AEME), cocaethylene (CE), norcocaethylene (NCE),
      and ecgonine ethyl ester (EEE) in blood, urine, and muscle. Available deuterated
      analogs of these analytes were used as internal standards. Proteins from blood
      and muscle homogenate were precipitated with cold acetonitrile. After the removal
      of acetonitrile by evaporation, the supernatants and urine were subjected to
      solid-phase extraction. The eluted analytes were converted to their hydrochloride
      salts and derivatized with pentafluoropropionic anhydride and 2,2,3,3,3
      pentafluoro-1-propanol. The derivatized products were analyzed by a gas
      chromatograph (GC)/mass spectrometer by selected ion monitoring. The limit of
      detection (LOD) for COC, BZE, NCOC, EME, CE, NCE, and EEE was 2ng/ml, while the
      LODs for BNE, ECG, HBZE, and AEME were 25, 640, 50, and 13 ng/ml, respectively.
      This method was successfully applied in analyzing 13 case samples from aviation
      accident pilot fatalities and motor vehicle operators. AEME concentrations found
      in the 13 samples were consistent with those produced solely by the GC inlet
      pyrolysis of COC controls in blood. Anhydroecgonine cannot be used as a marker
      for the abuse of COC by smoking because it is also pyrolytically produced from
      COC metabolites on the GC inlet. The developed method can be effectively adopted
      for analyzing COC and related compounds in urine, blood, and muscle by a single
      extraction with increased sensitivity through formation of hydrochloride salts
      and using a one-step derivatization.

PMID- 16428008
TI  - Examining the status of special education students: implications for pediatric
      nurses.

PMID- 16428009
TI  - Can easy-to-read immunization information increase knowledge in urban low-income
      mothers?
AB  - This article describes a pilot study that (1) assessed the self-report of highest
      grade completed in school and the actual reading and comprehension skills of low
      income mothers whose children receive immunizations in urban public clinics and
      (2) tested the effectiveness of a nursing intervention on immunization knowledge
      using revised easy-to-read written education materials. Thirty-seven mothers were
      randomized either to a control group (asked to read the standard vaccine
      information sheets) or to an experimental group (asked to read the revised
      immunization pamphlets). Although there was a modest increase in immunization
      knowledge for both groups, it was not significant. Thus, simplifying information
      alone may not increase parental knowledge.

PMID- 16428010
TI  - Pediatric anxiety: child life intervention in day surgery.
AB  - Although many hospitals offer a surgical preparation program to children and
      families, minimal research has been conducted specifically on preparation by
      child life specialists. The purpose of this double-blind intervention study was
      to determine if children prepared for day surgery by a child life specialist
      exhibited less anxiety than those who received routine standard of care. One
      hundred forty-two children, aged between 5 and 11 years old, undergoing elective
      otolaryngology surgery completed the study. The "Child Drawing: Hospital"
      instrument developed by Clatworthy, Simon, and Tiedeman [Clatworthy, S., Simon,
      K., & Tiedeman, M. E. (1999). Child Drawing: Hospital - An instrument designed to
      measure the emotional status of hospitalized school-aged children. Journal of
      Pediatric Nursing, 14, 2-9] was used to determine children's anxiety levels
      preintervention and postintervention. Eighty children received formal preparation
      for their surgeries by a child life specialist and 62 received no intervention.
      The data were analyzed using a repeated-measures model with intervention, age,
      sex, and level of surgery for main effects. The anxiety score change was
      significantly better for the patients in the child life intervention group than
      for those in the nonintervention group, F(1,135) = 4.24, p = .04. The increase in
      anxiety scores in the nonintervention group suggests that children could benefit
      from preoperative preparation. Health professionals, including nurses, may impact
      children's abilities to cope with a surgical process. The information in this
      study will be useful in deciding whether all children, not just those with a
      perceived need, should be prepared prior to an elective day surgery.

PMID- 16428011
TI  - Changes in sleep, food intake, and activity levels during acute painful episodes
      in children with sickle cell disease.
AB  - As part of a larger study that examined pain experience, pain management, and
      pain outcomes among children with sickle cell disease, functional status (sleep,
      food intake, and activity levels) was examined during hospitalization for acute
      painful episodes. Children were asked to rate the amount of pain they experienced
      as well as the amount of time they slept, the amount of food they ate, and the
      amount of activity they had everyday. Children reported high levels of pain,
      which showed only a small decrease throughout hospitalization, and had disrupted
      sleep and wake patterns, decreased food intake, and decreased activity levels.
      Nurses need to routinely monitor functional status during acute painful episodes
      so that strategies to promote adequate sleep, food intake, and activity may be
      incorporated to minimize long-term negative outcomes in children with sickle cell
      disease.

PMID- 16428012
TI  - Bicycle helmets: overcoming barriers to use and increasing effectiveness.
AB  - Bicycle riding is a popular recreational activity among children, yet it is not
      without potential severe consequences such as traumatic brain injury and death.
      Despite available information attesting to the benefits of the use of bicycle
      safety helmets, many children still do not wear them. There are several promoting
      and discouraging factors that influence wearing bicycle helmets. The purposes of
      this article are to (1) explore current research and discuss these promoting and
      obstructing factors to child bicycle helmet use and to (2) provide
      recommendations for improving the compliance of bicycle helmet use among
      children. Results of the literature review have significant implications for
      improving the safety of children.

PMID- 16428013
TI  - Effective weight loss for overweight children: a meta-analysis of intervention
      studies.
AB  - Childhood overweight has increased in the United States. Success of weight-loss
      programs has been limited (Barlow, S.E., & Dietz, W.H. (1998). Obesity evaluation
      and treatment: Expert committee recomendations. Pediatrics, 102, e29.). The
      purpose of this investigation was to systematically examine the effectiveness of
      weight-loss interventions for children. For this meta-analysis, seven weight-loss
      intervention studies were coded and quality index scores calculated. The
      interventions had a significant positive effect on weight-loss average d = 0.95,
      with a 95% confidence interval of 0.79 to 1.11. Limited interventional studies
      with effective long-term maintenance of weight loss in children are available in
      the literature. However, there are effective methods for weight loss in children.

PMID- 16428014
TI  - Baby-mother nourishment.

PMID- 16428015
TI  - Major stressors and their effects on the well-being of children with cancer.
AB  - An in-depth exploratory study identified major stressors experienced by children
      diagnosed with cancer. Four themes were used to analyze data from a series of
      focus group discussions and individual interviews with children, parents,
      hospital professionals, and hospital teachers (N = 35). First, major stressful
      events were reported by the children, their parents, and hospital professionals.
      Second, the effects of major stressors on the well-being of the children, their
      families, school, and hospital personnel were determined. Third, the children
      reported the consequences of major stressors on their physical and emotional well
      being. Fourth, the children's use of effective coping mechanisms was determined.
      The results revealed that the major stressors for children with cancer were
      treatment procedures (e.g., chemotherapy), loss of control, the hospital
      environment, relapses, and fear of dying. In addition, the children cited body
      image issues, ongoing lack of self-esteem, and issues relating to the preparation
      for transition back into real world situations (e.g., school).

PMID- 16428016
TI  - Knowledge and perceptions of parents regarding child sexual abuse in Botswana and
      Swaziland.
AB  - This study sought to explore the phenomenon of child sexual abuse by
      investigating the knowledge and perceptions of parents regarding this problem in
      Botswana and Swaziland. Although there are no published studies on child sexual
      abuse in Botswana and Swaziland, literature elsewhere has indicated that child
      abuse and prostitution prevail in Southern African Development Community
      countries and that children still continue to be rape victims within and outside
      the family structure [Muwanigwa, V. (1996). Child Abuse Demands More Preventive
      Measures. Harare: Zimbabwe. (Southern Africa News Features Southern African
      Research and Documentation Center)]. In Botswana in 1998, there were 300 cases of
      child abuse reported, of which 33 were sexual abuse cases. The same year in
      Swaziland, >50% of child abuse cases were sexual abuse related. In addition, the
      same year in Swaziland, >50% of sexual abuse case patients reporting for
      counseling were children younger than 21 years. Respondents of the study included
      8 men (1 from Swaziland and 7 from Botswana) and 10 women (3 from Swaziland and 7
      from Botswana) who were parents aged between 26 and 70 years; they were
      determined by way of purposive sampling. A focused interview guide with open
      ended questions was used to collect data, and measures to ensure trustworthiness
      and ethical considerations were adhered to. Analysis of data was facilitated by
      categorization of themes and concepts and coding systems. The results of the
      study showed that the respondents acknowledged the prevalence of child sexual
      abuse in Botswana and Swaziland and further demonstrated their knowledge of the
      predisposing factors, perpetrators of the problem, and effects of sexual abuse on
      children. They placed major emphases on community involvement in fighting against
      the problem; appropriate education of children, parents, families, and community
      members about child sexual abuse; and improvement on the laws that protect
      children against sexual abuse to successfully curb the problem.

PMID- 16428018
TI  - Position statement on exercise and physical activity.

PMID- 16428017
TI  - Using nurse shadowing as the focus for a recruitment program.
AB  - The nurse recruitment program at our private children's hospital provides an
      opportunity for family members of employees who are interested in becoming a
      nurse to learn more about pediatric nursing. This article describes our 5-hour
      recruitment program that includes didactic information, a hospital tour, and
      clinical experience through "nurse shadowing." Participants, presenters, and
      nurse preceptors have favorably evaluated this program. Programs like this can be
      used by other institutions to encourage and maintain interest in nursing and the
      health care professions.

PMID- 16428019
TI  - Estrogenic properties of isoflavones derived from Millettia griffoniana.
AB  - In most developing countries, 70-80% of the population still resort to
      traditional medicine for their primary health care. This medicine utilises
      medicinal plants which are traditionally taken as concoction and infusion. The
      root and stem bark of Millettia griffoniana (Leguminosae), has been reported to
      contain isoflavonoids, alkaloids, and diterpenoids. The possible benefit of some
      bioactive isoflavones derived from M. griffoniana prompted us to screen them for
      estrogenic activity. Six isoflavones and coumarin derived from M. griffoniana
      (bail) namely, compound nos. 1-6 (Fig. 1) were tested for their potential
      estrogenic activities in three different estrogen receptor alpha (ERalpha)
      dependent assays. In a yeast-based ERalpha assay, all test substances and 17beta
      estradiol as endogenous agonist, showed a significant induction of beta
      galactosidase activity. The test compounds at the concentration of 5 x 10(-6) M
      could achieve 59-121% of the beta-galactosidase induction obtained with 10(-8) M
      17beta-estradiol (100%). In the reporter gene assay based on stably transfected
      MCF-7 cells (MVLN cells), the estrogen responsive induction of luciferase was
      also stimulated by the M. griffoniana isoflavones. In Ishikawa cells, all
      substances exhibited estrogenic activity revealed by the induction of alkaline
      phosphatase (AlkP) activity. The estrogenic activities of isoflavones from M.
      griffoniana could be completely suppressed by the pure estrogen antagonist, ICI
      182,780, suggesting that the compounds exert their activities through ERalpha.
      Although all substances showed estrogenic effects, 4'-methoxy-7-O-[(E)-3-methyl-7
      hydroxymethyl-2,6-octadienyl]isoflavone (7-O-DHF), Griffonianone C (GRIF-C), and
      3',4'-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone (7-O-GISO) were
      found to be the most potent of tested substances. In summary, estrogenic
      activities of the isoflavones derived from M. griffoniana were described for the
      first time using reporter gene assays and the estrogen-inducible AlkP Ishikawa
      model.

PMID- 16428020
TI  - Eugenol depresses synaptic transmission but does not prevent the induction of
      long-term potentiation in the CA1 region of rat hippocampal slices.
AB  - Using field potential recording in the CA1 region of the rat hippocampal slices,
      the effects of eugenol on synaptic transmission and long-term potentiation (LTP)
      were investigated. Population spikes (PS) were recorded in the stratum pyramidal
      following stimulation of stratum fibers. To induce LTP, eight episodes of theta
      pattern primed-bursts (PBs) were delivered. Eugenol decreased the amplitude of PS
      in a concentration-dependent manner. The effect was fast and completely
      reversible. Eugenol had no effect on PBs-induced LTP of PS. It is concluded that
      while eugenol depresses synaptic transmission it does not affect the ability of
      CA1 synapses for tetanus-induced LTP and plasticity.

PMID- 16428021
TI  - Anti-inflammatory activity of alkanoids and triterpenoids from Trichodesma
      amplexicaule Roth.
AB  - The phytochemical investigation of Trichodesma amplexicaule guided by bioassay,
      to isolation of triterpenoids and aliphatic phytoconstituents. To evaluate the
      anti-inflammatory activities of isolated phytoconstituents, models with
      carrageenan-induced acute arthritis and complete Freund's adjuvant (CFA)-induced
      chronic arthritis in rats were conducted. The investigated results showed that
      alkanoic acid significantly inhibited the carrageenan-induced acute arthritis.
      Moreover, alkane also supressed the development of chronic arthritis induced by
      CFA. It has been reported that alkane was the major phytoconstituent (1.03 +/-
      0.00135%) in in vivo studies.

PMID- 16428023
TI  - Prostaglandin-H-synthase (PGHS)-1 and -2 microtiter assays for the testing of
      herbal drugs and in vitro inhibition of PGHS-isoenzyms by polyunsaturated fatty
      acids from Platycodi radix.
AB  - In order to test inhibition of prostaglandin-H-synthase-1 and -2 (PGHS-1 and -2)
      by plant extracts, we have established two enzyme based in vitro assays with
      enzyme immunoassay (EIA) evaluation. The assays have been evaluated with known
      synthetic inhibitors and with plant extracts. In a screening of traditionally
      used Chinese herbs for anti-inflammatory activity, a series of n-hexane and
      dichloromethane extracts showed significant inhibitory effect in comparison with
      the known specific PGHS-2 inhibitors NS-398 (IC(50) = 2.6 microM) and nimesulide
      (IC(50) = 36 microM). The lipophilic extracts of the Chinese drug Jiengeng, the
      dried roots of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae), showed
      good inhibitory activity against both PGHS isoenzymes. The directly prepared DCM
      extract exhibited better activity against PGHS-2 (IC(50) = 4.0 microg/ml) than
      against PGHS-1 (IC(50) = 17.6 microg/ml). We identified fatty acids as main
      active constituents and quantified them. Linoleic acid showed the highest content
      (ca. 20% of the dried extract) and a high and preferential PGHS-2 inhibitory
      activity (IC(50) (PGHS-1) = 20 microM; IC(50) (PGHS-2) = 2 microM). The
      comparison of the concentration of linoleic acid and the inhibitory activity of
      the direct DCM-extract showed, that linoleic acid is mainly responsible for the
      in vitro activity of the extract on PGHS-2.

PMID- 16428022
TI  - Butea monosperma and chemomodulation: protective role against thioacetamide
      mediated hepatic alterations in Wistar rats.
AB  - The present study was carried out to study the effect of Butea monosperma, a
      known liver acting drug on the tumor promotion related events of carcinogenesis
      in rat liver. Thioacetamide (TAA) was used to induce tumor promotion response and
      oxidative stress and caused significant depletion in the detoxification and
      antioxidant enzyme armory with concomitant elevation in malondialdehyde (MDA)
      formation, hydrogen peroxide (H(2)O(2)) generation, ornithine decarboxylase (ODC)
      activity and unscheduled DNA synthesis. However, B. monosperma pretreatment at
      two different doses restored the levels of the above-said parameters (p < 0.001)
      in a dose-dependent manner. The alcoholic extract of B. monosperma used in the
      present study seems to offer dose-dependent protection and maintain the
      structural integrity of hepatic cells. This was evident from the significant
      reduction in TAA-induced serum GOT, GPT, Lactate dehydrogenase (LDH) and gamma
      Glutamyl transpeptidase activity (GGT) activities (p < 0.001). These
      investigations validate the use of B. monosperma in liver disorders by Ayurvedic
      physicians. Overall results indicate that the methanolic extract of B. monosperma
      possesses hepatoprotective effects and also it might suppress the promotion stage
      via inhibition of oxidative stress and polyamine biosynthetic pathway.

PMID- 16428024
TI  - In vitro effects of propolis on Giardia duodenalis trophozoites.
AB  - In order to improve the current chemotherapy of Giardia infection, potential
      antigiardial agents have been screened, including natural products. Propolis, a
      resinous hive product collected by bees, has attracted attention as a useful and
      popular substance with several therapeutic activities. The present study was
      carried out aiming to evaluate the in vitro effects of an ethanolic extract of
      propolis on the growth and adherence of Giardia duodenalis trophozoites. Propolis
      inhibited the growth of trophozoites and the level of inhibition varied according
      to the extract concentration and incubation times. The highest reduction of
      parasite growth was observed in cultures exposed to 125, 250 and 500 microg/ml of
      propolis, in all incubation periods (24, 48, 72 and 96 h). Growth reduction by
      50% was observed in 125 microg/ml propolis-treated cultures, while the
      concentrations of 250 and 500 microg/ml were able to inhibit growth by more than
      60%. Propolis also inhibited parasite adherence and all assayed propolis
      concentrations promoted the detachment of trophozoites. Light microscope
      observations revealed changes of the pear-shaped aspect of the cell and reduction
      of flagellar beating frequency in the great part of the trophozoites. Our results
      hold the perspective for the utilization of propolis as an antigiardial agent.

PMID- 16428025
TI  - Comparative antiplasmodial, leishmanicidal and antitrypanosomal activities of
      several biflavonoids.
AB  - The antiplasmodial, leishmanicidal and antitrypanosomal activities of eight
      natural biflavonoids were estimated in vitro on a chloroquine-resistant strain of
      Plasmodium falciparum, axenically grown Leishmania donovani amastigotes and
      Trypanosoma cruzi trypomastigotes and Trypanosoma brucei rhodesiense bloodstream
      forms. Lanaroflavone showed the highest antiplasmodial activity (IC(50) = 0.48
      microM), isoginkgetin was the most active leishmanicidal compound (IC(50) = 1.9
      microM), whereas ginkgetin (IC(50) = 11 microM) and isoginkgetin (IC(50) = 13
      microM) showed the best antitrypanosomal activity in our assays. The cytotoxicity
      and the selectivity indices for the most active compounds were also estimated.
      Lanaroflavone exhibited a high selectivity index value (SI = 159), indicating
      selective antiplasmodial activity.

PMID- 16428026
TI  - The cytotoxicity of naturally occurring styryl lactones.
AB  - We extracted and isolated three natural styryl lactones from Goniothalamus
      griffithii Hook f. Thoms and investigated their cytotoxicity on a panel of three
      hepatocyte cell lines, HepG2, drug resistant HepG2 (HepG2-R) and primary cultured
      normal mice hepatocyte in order to find candidates of potential anti-cancer drugs
      which have low toxicity on normal cells and high effect on tumors or drug
      resistant tumors. All the three styryl lactones showed evident cytotoxic
      activities on both HepG2 and HepG2-R cell lines; however, gonithalamin and
      goniodiol shows less toxicity on normal mice hepatocyte as the IC(50) values of
      them on normal mice hepatocyte were about three times of that on HepG2.
      Morphological observation and cell cycle analysis were employed to elucidate the
      mechanisms of cytotoxicity of the tested compounds. Many apoptotic cells were
      observed in gonithalamin- and altholactone-treated cells, whereas, cells with
      chromosomes gathered at the equator were easily found in goniodiol-treated
      cultures. The analysis of cell cycle showed that G(2)/M arrest contributed to
      goniothalimin- and gonidiol-caused cell death and apoptosis was the cause of
      gonithalamin- and altholactone-induced cell death. Our results suggest that the
      three styryl lactones may be prospectively developed into anti-tumor drugs,
      especially on treating drug-resistance tumor after structure modification.

PMID- 16428027
TI  - Assessment of the antibacterial activity of galangin against 4-quinolone
      resistant strains of Staphylococcus aureus.
AB  - The flavonol galangin is present in numerous plants and is a major constituent of
      Helichrysum aureonitens, a perennial herb used by South African indigenes to
      treat infection. In the present study, the antibacterial activity of galangin was
      assessed against 17 strains of 4-quinolone resistant S. aureus using an agar
      dilution assay. It was determined that the flavonol had a minimum inhibitory
      concentration (MIC) of approximately 50 microg/ml against 16 of these strains,
      including those which exhibited 250- and 500-fold increases in norfloxacin
      resistance. The remaining one strain, which possessed an amino acid alteration in
      the GrlB subunit of topoisomerase IV, had increased susceptibility to galangin.
      Control strains of 4-quinolone sensitive S. aureus were also found to have MICs
      of 50 microg/ml. The topoisomerase IV enzyme may therefore be implicated in the
      antibacterial mechanism of action of galangin. Clearly however, there is no cross
      resistance between galangin and the 4-quinolones, and the flavonol therefore
      warrants further investigation as an antibacterial agent.

PMID- 16428028
TI  - Kavalactones fail to inhibit alcohol dehydrogenase in vitro.
AB  - In recent years, Kava kava (Piper methysticum, Forst. f., Piperaceae), a
      folkloric beverage and popular herbal remedy, has been implicated in a number of
      liver failure cases. Many hypotheses as to the mechanism of its hepatotoxicity,
      for example interactions with other co-ingested medication, have been postulated.
      This present study investigated whether pharmacokinetic interactions between kava
      constituents and alcohol via alcohol dehydrogenase (ADH) inhibition by individual
      kavalactones might explain its claimed hepatotoxic effects. Four kavalactones,
      (+/-)-kavain, methysticin, yangonin and desmethoxyyangonin, fail to inhibit ADH
      in vitro at 1, 10 or 100 microM concentrations.

PMID- 16428029
TI  - Inhibition of CCl4-induced liver fibrosis by Piper longum Linn.?
AB  - This study was carried out to evaluate the antifibrotic effect of ethanol extract
      of the fruits of Indian herb Piper longum Linn. Liver fibrosis was induced in
      rats by CCl(4) administration. The extent of liver fibrosis was assessed by
      measuring the level of liver hydroxy proline (HP) and serum enzyme levels.
      Following CCl(4) administration HP was significantly increased and serum enzyme
      levels were elevated. Treatment with the ethanol extract of Piper longum Linn.
      reduced the HP and also the serum enzymes. The liver weight that increased
      following CCl(4) administration due to the deposition of collagen was reduced by
      the ethanol extract. Hence, it is concluded that this extract inhibits liver
      fibrosis induced by CCl(4).

PMID- 16428030
TI  - Safety of St. John's Wort extract compared to synthetic antidepressants.
AB  - The clinical efficacy of some standardized St. John's Wort extracts (SWEs) such
      as WS((R)) 5570, WS((R)) 5572 or LI 160 in the treatment of mild, moderate and
      severe major depression has been demonstrated in 38 controlled clinical trials
      and two recent meta-analyses. Sixteen post-marketing surveillance studies with
      such preparations, based on a total of 34,804 patients, recorded an incidence of
      adverse events (AEs) among patients between 0% and 6%. Of these studies, the four
      large-scale surveillance studies with a total of 14,245 patients recorded a rate
      of AEs ranging from 0.1% to 2.4% and a drop-out rate due to AEs of 0.1-0.9%. This
      is at least ten-fold lower than that recorded with synthetic antidepressants. AEs
      associated with SWE treatment were mild and transient in nearly all cases. As
      with synthetic antidepressants, pharmacokinetic interactions may occur
      occasionally as a result of activity changes of drug-metabolising and drug
      transporting proteins, especially CYP 3A4 and P-gp. Risks to the patient are not
      caused by SWE but by drugs with a narrow therapeutic range. Consequently, SWE
      preparations should not be taken concurrently with other antidepressants, with
      coumarin-type anticoagulants, the immunosuppressants cyclosporine and tacrolimus,
      protease and reverse transcriptase inhibitors used in anti-HIV treatment or with
      certain antineoplastic agents. However, such cases are extremely rare and, with
      medical supervision, easily avoided. In conclusion, the safety of SWE must be
      considered more favourable than that of synthetic antidepressants.

PMID- 16428031
TI  - Herbal remedies for anxiety - a systematic review of controlled clinical trials.
AB  - Anxiety is a prominent indication for herbal medicine. This systematic review was
      therefore aimed at summarising the evidence for or against the anxiolytic
      efficacy of such treatments. Six databases were searched for all randomised
      clinical trials testing herbal monopreparations in the alleviation of anxiety.
      Seven such studies and one systematic review were located. Eight different
      herbals were studied. The herbal medicines, which, according to these data are
      associated with anxiolytic activity in humans, are Piper methysticum and Bacopa
      monniera. Only for kava were independent replications available. It was concluded
      that there is a lack of rigorous studies in this area and that only kava has been
      shown beyond reasonable doubt to have anxiolytic effects in humans.

PMID- 16428032
TI  - ILSMRs (intensifier of beta-lactam-susceptibility in methicillin-resistant
      Staphylococcus aureus) from Tara [Caesalpinia spinosa (Molina) Kuntze].
AB  - Four quinic acid gallates were isolated from the dried pods of Tara [Caesalpinia
      spinosa (Molina) Kuntze]. These compounds intensified the susceptibility of
      methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin. 3,4,5-Tri-O
      galloylquinic acid methyl ester (2) was the most effective compound of them.

PMID- 16428034
TI  - Epidemiology and molecular biology of Barrett esophagus.
AB  - Over the past three decades, there has been a marked change in the epidemiology
      of esophageal malignancy, with an increasing incidence of esophageal
      adenocarcinoma. The reasons for this are largely unknown and remain
      controversial, but several lifestyle risk factors have been proposed, including
      gastroesophageal reflux disease (GERD). It is hypothesized that chronic GERD
      results in acute mucosal injury, promotes cellular proliferation, and induces
      specialized columnar metaplasia (Barrett esophagus). Progression of Barrett
      esophagus to invasive adenocarcinoma is reflected histologically by the
      metaplasia-dysplasia-carcinoma sequence. Dysplasia is widely regarded as the
      precursor of invasive cancer, and high-grade dysplasia in Barrett epithelium is
      frequently associated with esophageal adenocarcinoma. Although several molecular
      alterations have been described in Barrett esophagus, it is anticipated that
      relatively few will prove to be clinically useful. To date, biomarkers which
      currently appear to predict the progression of Barrett esophagus to invasive
      malignancy include aneuploidy, loss of heterozygosity of 17p (implicating the p53
      tumor suppressor gene), and cyclin D1 protein overexpression, and with further
      validation, will most likely be incorporated into routine clinical practice. It
      is anticipated that models incorporating objective scores of sociodemographic and
      lifestyle risk factors (ie, age, gender, body mass index), severity of reflux
      symptoms, endoscopic and histologic findings, and an assessment of a panel of
      biomarkers will be developed to further define subsets of patients with Barrett
      esophagus at increased risk for malignant progression, thereby permitting the
      development of more rational endoscopic surveillance and screening programs.

PMID- 16428035
TI  - Barrett's esophagus: pathologic considerations and implications for treatment.
AB  - Barrett's esophagus (BE) is a complication of chronic reflux that results in the
      replacement of esophageal squamous epithelium with columnar epithelium. BE is
      endoscopically recognized and pathologically confirmed. The presence of goblet
      cells is diagnostic. The pathologist must also determine if dysplasia or invasive
      cancer is present. Acceptable terms for dysplasia are no dysplasia, indefinite
      for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). It can
      be difficult to differentiate HGD from intramucosal cancer (IMC) in an endoscopic
      biopsy specimen. Treatment based on this differentiation is problematic.
      Indications for treatment of BE are similar to those of patients without BE.
      Treatment will not cause clinically significant regression of BE or prevent
      progression to cancer. Cancer development following successful antireflux surgery
      is uncommon.

PMID- 16428036
TI  - Barrett's esophagus: diagnostic approaches and surveillance.
AB  - In an effort to identify those patients at risk for developing esophageal
      adenocarcinoma, the American College of Gastroenterology recommends screening
      endoscopy in patients with chronic gastroesophageal reflux disease. Surveillance
      endoscopy is recommended every 3 years in those patients without dysplasia. For
      those patients with verified low-grade dysplasia, yearly surveillance endoscopy
      is recommended. In the case of high-grade dysplasia (HGD), either intensive
      endoscopic surveillance (focal HGD) or ablation/resection can be performed
      (multifocal HGD). Both observational and cost-effectiveness analyses suggest a
      potential benefit of endoscopic screening and surveillance, though these findings
      remain to be validated in controlled clinical trials. The development of new
      endoscopic imaging modalities may enhance the yield of biopsies obtained during
      screening and surveillance regimens.

PMID- 16428037
TI  - Laser ablation therapies for Barrett's esophagus.
AB  - The metaplastic change of the normal squamous epithelium of the distal esophagus
      into a specialized columnar epithelium is known as Barrett's esophagus (BE) and
      is associated with an increased risk of adenocarcinoma of the esophagus. It is a
      frequent complication of gastroesophageal reflux disease (GERD) and up to 10% of
      patients with GERD suffer from BE. The progression to dysplasia increases the
      risk of cancer development and the annual risk of developing cancer in Barrett's
      esophagus is estimated to be 0.5% per year. The management of BE with high grade
      dysplasia (HGD) is controversial. Recent innovations in endoscopic therapy have
      allowed for the development of multiple endoscopic techniques, such as
      photodynamic therapy (PDT), argon plasma coagulation (APC), and endoscopic
      mucosal resection. In this article, we will discuss primarily photodynamic
      therapy, and other ablative technologies such as argon plasma coagulation in the
      treatment of BE.

PMID- 16428038
TI  - Endoscopic mucosal resection and vagal-sparing esophagectomy for high-grade
      dysplasia and adenocarcinoma of the esophagus.
AB  - Once a rare tumor, adenocarcinoma of the esophagus is currently the cancer with
      the fastest rising incidence in America. In addition to the increasing prevalence
      of the disease, surveillance programs for patients with Barrett's have led to the
      identification of increasing numbers of patients with high-grade dysplasia or
      early-stage esophageal adenocarcinomas. Although traditional esophagectomy is
      curative in the majority of these patients, associated morbidity and mortality
      remains a hurdle for patient acceptance of the procedure. New endoscopic and
      surgical therapies offer the potential of decreased morbidity, but do not include
      a lymphadenectomy, and consequently, are not appropriate in patients that have a
      significant risk of lymph node metastases. Endoscopic mucosal resection allows
      precise determination of the depth of tumor invasion and facilitates accurate
      local staging of early esophageal cancers. A vagal-sparing esophagectomy
      accomplishes the goal of removing the diseased esophagus while minimizing the
      physiologic impact of an esophagectomy in patients with early-stage esophageal
      cancer.

PMID- 16428039
TI  - Surgical aspects of the patient with high-grade dysplasia.
AB  - The incidence of esophageal cancer has increased dramatically in the Western
      population in the last 2 decades. In 1975, about three fourths of the esophageal
      neoplasms were squamous cell carcinomas and the remainder were adenocarcinomas.
      During the last 2 to 3 decades, this pattern has changed dramatically and the
      incidence of squamous cell carcinomas has declined while the incidence of
      adenocarcinomas has increased. The reason for this dramatic increase is not
      clear, but gastro esophageal reflux disease, obesity and Barrett's esophagus have
      been identified as risk factors. High grade dysplasia in Barrett's esophagus is a
      premalignant condition which can progress to invasive adenocarcinoma. In this
      article, we discuss the natural history of high grade dysplasia (HGD),
      difficulties in the diagnosis, the incidence of adenocarcinoma in resected
      specimens and the surgical aspects in the treatment of HGD, including minimally
      invasive esophagectomy.

PMID- 16428041
TI  - New directions in the medical management of heart failure.
AB  - Like the introduction of digitalis more than 200 years ago, novel medical
      therapies today have the potential to significantly alter the course of heart
      failure (HF) and save thousands of lives. This review outlines new directions in
      HF medical management beyond the foundation of neurohormonal blockade.
      Furthermore, the role of novel risk factors in HF such as chronic renal
      insufficiency, anemia, and sleep apnea present tantalizing therapeutic targets to
      extend the morbidity and mortality benefits of current therapies. The course of
      time will tell which of these risk factors and therapies can hold promise, given
      the recent litany of negative trials in the HF arena. Advancements in molecular
      and genetic techniques have allowed us to begin to consider patient specific
      therapies and lay the groundwork for even further improvements in treatment of
      symptomatic HF. Finally, advances in telemedicine and device technology will
      allow the clinician to remotely monitor useful clinical parameters such as heart
      rate variability and pulmonary filling pressures to make more informed clinical
      decision-making and improve outcomes.

PMID- 16428042
TI  - Gene therapy for heart failure.
AB  - Congestive heart failure (CHF) remains a leading cause of morbidity and mortality
      in the United States and in many other countries. Current heart failure
      therapies, including multidrug treatment regimens, biventricular pacing, and
      mechanical support such as left ventricular assist devices, are often hindered by
      limited benefits or significant associated procedural complications or side
      effects. Therefore, new forms of treatment, which could ideally target the
      underlying biological processes affecting the ailing cardiomyocyte, would be of
      significant potential benefit to the population of individuals with CHF. Gene
      transfer strategies, including modification of cellular contractile signaling and
      regulatory pathways, represent a promising new form of such biologic therapy for
      heart disease.

PMID- 16428043
TI  - Cell therapy for heart failure--muscle, bone marrow, blood, and cardiac-derived
      stem cells.
AB  - Heart failure (HF) affects a rapidly growing population of patients. Despite
      improvements in the understanding and therapy of many stages of cardiovascular
      disease, there has been little progress in treating HF. In the late-stage
      disease, current options are cardiac transplantation and mechanical support-
      options that are limited to a small patient collective. The ischemically injured
      failing heart lacks contractile myocardium, functional vasculature, and
      electrical integrity, which has made treatment of the underlying injury untenable
      in the past. Restoring all of these components seems an overwhelming challenge.
      Yet, the concept of cell therapy--tissue repair by transplantation of stem and
      progenitor cells--has opened new potential options for patients with heart
      failure. Skeletal myoblasts, bone marrow, and blood-derived stem cells have all
      shown considerable myogenic and angiogenic potential in vitro and have rapidly
      moved from bench to bedside. A number of nonrandomized, non-placebo-controlled
      safety and feasibility studies have been reported and now double-blinded
      randomized controlled trials are underway. Despite this rapid clinical pace, the
      exact mechanisms underlying the functional benefits of different cell types are
      not well understood. Instead, multiple similar mechanism have been ascribed to
      virtually every cell type. Thus, while the field is exciting and offers
      unheralded promise to treat patients with CVD, we must proceed with due diligence
      and caution. Only a deep understanding of the benefits versus the risks, and the
      mechanisms involved in cell-mediated cardiac repair, will allow us to design
      clinically valuable tools and fulfill the potential of this exciting 21st century
      approach to treating cardiovascular disease.

PMID- 16428044
TI  - Clinical results with the Acorn cardiac restraint device with and without mitral
      valve surgery.
AB  - Progressive left ventricular (LV) remodeling is part of the unfavorable natural
      history in patients with heart failure (HF). The CorCap Cardiac Support Device
      (CSD) is a mesh device that is implanted around the heart to reduce wall stress
      and the first therapy specifically designed to address LV remodeling. Early
      clinical studies have shown that the CSD is safe and associated with improvements
      in LV structure and function and patient symptoms. The CorCap was studied in the
      largest prospective randomized multicentered trial of a surgical device ever
      completed. The study demonstrated both safety and effectiveness of the CorCap in
      patients with advanced heart failure and remodeled ventricles.

PMID- 16428045
TI  - Experimental and clinical studies with the Paracor cardiac restraint device.
AB  - Progressive cardiac enlargement is a consequence of congestive heart failure
      (CHF) and a cause of further deterioration. Cardiac restraint devices are
      intended to interrupt and reverse this process, thereby improving the natural
      history of CHF. The Paracor restraint device is made from a superelastic nitinol
      mesh that exerts a small but continuous epicardial force to relieve left
      ventricular (LV) wall stress and to limit LV dilation. Animal studies have used
      various heart failure models. The data show the device reduces LV dilation after
      infarction, preserves LV contractility with rapid pacing, and avoids diastolic
      constriction in the embolization model. Ten patients in Europe and 10 in the
      United States have been implanted through a small thoracotomy incision without
      the use of cardiopulmonary bypass. Changes in LV size, functional status, and
      exercise performance have been measured, but the detailed data have not yet been
      presented or published. The device remains experimental, pending completion of
      additional clinical trials.

PMID- 16428046
TI  - Executive summary for the National Heart, Lung, and Blood Institute Working Group
      on next generation ventricular assist devices for destination therapy.

PMID- 16428047
TI  - Toward a strategy for consensus development on a quantitative approach to medical
      imaging.

PMID- 16428048
TI  - A quadratic model for combining quantitative diagnostic assessments from
      radiologist and computer in computer-aided diagnosis.
AB  - RATIONALE AND OBJECTIVES: Some computer-aided diagnosis (CAD) methods produce a
      quantitative diagnostic assessment (eg, likelihood of malignancy) based on
      computer image analysis that a radiologist who uses the computer aid must combine
      with his or her own assessment. Observer studies show that although CAD helps
      radiologists improve diagnostic performance, ad hoc use of computer aid can
      produce performance inferior to that of computer alone, indicating that
      radiologists are unable to incorporate computer assessment optimally into their
      final assessment. We describe a mathematical model for combining two correlated
      diagnostic assessments that may provide a basis for merging radiologists' ratings
      with computer assessments in a way that yields greater diagnostic accuracy than
      ad hoc merging by radiologists. MATERIALS AND METHODS: We calculate a likelihood
      ratio from the bivariate binormal model that describes joint probability density
      functions of latent decision variables of two correlated diagnostic assessments.
      To the extent that the bivariate binormal model is valid and that the model's
      parameters can be estimated reliably, results obtained in this way will be
      optimal because the likelihood ratio is the decision variable used by the ideal
      observer in any two-group classification task. We evaluated this method on two
      observer study datasets and in Monte Carlo simulations. RESULTS: This method
      produced better performance than achieved by radiologists when they incorporated
      computer assessment in an ad hoc way. Simulations show that with a large number
      of cases, this method can produce results indistinguishable from the ideal
      observer performance. CONCLUSIONS: This method can potentially help radiologists
      use quantitative computed diagnostic assessments optimally, thereby surpassing
      the computer in accuracy.

PMID- 16428049
TI  - The application of Markov theory to contrast-detail analysis.
AB  - RATIONALE AND OBJECTIVES: To improve the accuracy of contrast-detail (C-D)
      analysis, we have devised a new evaluation method of the detection performance in
      the C-D analysis by using the Markov process model. This article describes this
      new evaluation method and the results of applying it to the illustrative
      examples. MATERIALS AND METHODS: A commercially available C-D phantom was
      employed as a test object, and 20 phantom radiographs with an average background
      density of 0.8 were prepared. Thirty-five observers interpreted all phantom
      radiographs independently of each other with the room lights off. We assume the
      Markov model in which the selection of the smallest visible contrast for each row
      of disks with the same diameter depends only on the contrast selected as the
      smallest visible one for the same row in the just-before reading experiment. By
      using this Markov model, the contrast detectability for each disk diameter was
      calculated, and a C-D diagram was constructed based on these results. The
      conventional C-D diagram was also derived from the averages of contrast
      detectability obtained from the interpretations of all phantom radiographs.
      RESULTS: All C-D diagrams obtained from our devised method agreed well with each
      other and were in good accord with the conventional C-D diagram from the
      interpretations of all phantom radiographs. CONCLUSIONS: We have devised a new
      evaluation method of C-D analysis by using the Markov model and have shown this
      method will be consistent with the conventional evaluation method in the C-D
      analysis.

PMID- 16428050
TI  - Multiphase contrast medium injection for optimization of computed tomographic
      coronary angiography.
AB  - RATIONALE AND OBJECTIVES: Electron beam angiography is a minimally invasive
      imaging technique. Adequate vascular opacification throughout the study remains a
      critical issue for image quality. We hypothesized that vascular image
      opacification and uniformity of vascular enhancement between slices can be
      improved using multiphase contrast medium injection protocols. MATERIALS AND
      METHODS: We enrolled 244 consecutive patients who were randomized to three
      different injection protocols: single-phase contrast medium injection (Group 1),
      dual-phase contrast medium injection with each phase at a different injection
      rate (Group 2), and a three-phase injection with two phases of contrast medium
      injection followed by a saline injection phase (Group 3). Parameters measured
      were aortic opacification based on Hounsfield units and uniformity of aortic
      enhancement at predetermined slices (locations from top [level 1] to base [level
      60]). RESULTS: In Group 1, contrast opacification differed across seven
      predetermined locations (scan levels: 1st versus 60th, P < .05), demonstrating
      significant nonuniformity. In Group 2, there was more uniform vascular
      enhancement, with no significant differences between the first 50 slices (P >
      .05). In Group 3, there was greater uniformity of vascular enhancement and higher
      mean Hounsfield units value across all 60 images, from the aortic root to the
      base of the heart (P < .05). CONCLUSIONS: The three-phase injection protocol
      improved vascular opacification at the base of the heart, as well as uniformity
      of arterial enhancement throughout the study.

PMID- 16428051
TI  - Reproducibility of CT measurements of aortic valve calcification, mitral annulus
      calcification, and aortic wall calcification in the multi-ethnic study of
      atherosclerosis.
AB  - RATIONALE AND OBJECTIVES: Extracoronary calcifications may have clinical
      significance. The error in extracoronary calcification measurements is still
      unknown. Accurate quantification of calcifications of the aortic valve (AVC),
      mitral annulus (MAC), and aortic wall (AWC) may be possible by using cardiac
      computed tomography (CT). We sought to establish the interscan, interobserver,
      and intraobserver reproducibility of these measures in all cardiac CT scans in
      the Multi-Ethnic Study of Atherosclerosis. MATERIALS AND METHODS: We measured
      extracoronary calcifications in 100 randomly selected participants to assess
      interobserver, interscan, and intraobserver variability. Two scans were available
      for analysis in 99 of these participants, and we quantified thoracic aorta and
      valvular calcifications. RESULTS: Mean interscan variability of AVC was 9.7% +/-
      11.4% and 8% +/- 10.3% for Agatston and volume scores, with variability of the
      median at 6.4% and 5.5%, respectively (P > .05). MAC inter-reader variability was
      8.2% and 8.9%, with interscan variability of 28% and 33% and intrareader
      variability of 4% and 4.1%, respectively. For AWC, inter-reader variability was
      3%-7.1%, interscan variability was 17%-18%, and intrareader variability was 0.4%
      1.4%. CONCLUSION: AVC, MAC, and AWC measurements are sufficiently reproducible to
      allow serial investigations over a time suitable for clinical studies.

PMID- 16428052
TI  - Timing on 16-slice scanner and implications for 64-slice cardiac CT: do you start
      scanning immediately after breath hold?
AB  - RATIONALE AND OBJECTIVES: Slow heart rate and small changes in heart rate are
      factors for improving image quality on spiral cardiac computed tomography (CT).
      The purpose of this study is to investigate whether it is possible to improve non
      enhanced cardiac CT quality by delaying the data-acquisition window after breath
      hold. MATERIALS AND METHODS: Electrocardiograph files (n = 240) for 16-slice non
      enhanced cardiac CT scans were analyzed. Mean heart rates and maximal changes in
      heart rates between adjacent cardiac cycles were compared between phase 1
      (defined as cardiac cycles 1-5), phase 2 (cardiac cycles 2-6), ... , and phase 6
      (cardiac cycles 6-10). RESULTS: Heart rates gradually increased by phases, but
      were limited to a range of 66.8-68.0 beats/min. Maximal changes in heart rates
      were 2.5 beats/min (phase 1) at the highest and 1.3 beats/min (phases 5 and 6) at
      the lowest (t-test; P < .01). Maximal changes in heart rates for more than five
      beats/min occurred in 24, eight, and eight patients on phases 1, 5, and 6,
      respectively (chi-square test; P < .01). CONCLUSION: The delayed scan (four or
      five cardiac cycles after breath hold) has the potential to improve the quality
      of non-enhanced cardiac CT.

PMID- 16428053
TI  - Noninvasive analysis of coronary artery disease with combination of MDCT and
      functional MRI.
AB  - RATIONALE AND OBJECTIVES: We evaluated the diagnostic accuracy of an eight-row
      multidetector computed tomography coronary angiography (MDCT-CA) in detecting
      high-grade (>50%) stenoses in the three main coronary arteries in patients with
      coronary artery disease (CAD). Side branches were excluded. We correlated
      magnetic resonance imaging (MRI) findings of the myocardium with MDCT-CA of the
      coronary arteries. MATERIALS AND METHODS: Fourteen CAD patients underwent
      conventional coronary angiography (CCA), MDCT-CA, and MRI. We determined the
      calcium burden with non-enhanced MDCT scan. Then MDCT-CA was performed after
      intravenous contrast injection during a single breathhold. The left ventricular
      (LV) MR cine imaging was assessed at rest and perfusion defects were observed
      during pharmacologic stress after contrast administration. Delayed contrast
      enhanced MRI was performed to picture infarctions. RESULTS: MDCT-CA had
      sensitivity 82%, specificity 94%, positive predictive value 79%, and negative
      predictive value 95% of stenoses of more than 50% in the main coronary arteries
      when compared with CCA. LV wall dysfunction, perfusion defects, and infarctions
      were detected in 50%-78% of sectors assigned to calcifications or stenoses, but
      also in sectors supplied by normally perfused coronary arteries. CONCLUSIONS: CCA
      and MDCT-CA revealed comparable results in evaluating stenotic lesions above 50%
      in the main subepicardial coronary branches. There were no significant
      correlations between the degree of stenosis or calcification at MDCT-CA and the
      MR findings, but the combined information of MDCT-CA and MRI showed the
      variability of myocardial changes in regions perfused by significantly stenosed,
      calcified, and normal main coronary arteries.

PMID- 16428054
TI  - Automated technique for angiographic determination of coronary blood flow and
      lumen volume.
AB  - RATIONALE AND OBJECTIVES: Visual interpretation of angiographic images has been
      shown to be inadequate for assessing the severity of intermediate coronary
      stenoses. An approach for evaluating both the anatomic and functional impact of a
      stenosis is needed. An automated technique for determining both coronary blood
      flow and lumen volume based on a first-pass analysis (FPA) of coronary angiograms
      and a template matching algorithm was evaluated. MATERIALS AND METHODS: Coronary
      angiograms of a swine animal model were obtained during power injections of
      contrast material into the left coronary ostium. Background anatomy was
      subtracted with an automated phase matching program. A template matching
      algorithm and first-pass analysis were then used to quantify coronary blood flow
      and lumen volume. Coronary blood flow and lumen volume measurements were
      validated with a transit-time ultrasound flow probe and a polymer cast of the
      coronary arteries, respectively. RESULTS: In 14 independent comparisons, the mean
      coronary blood flow measured with FPA showed strong correlation with the mean
      flow measured with the ultrasound flow probe (Q(FPA) = 0.88Q(probe) - 1.99; r =
      0.977; standard error of estimate = 3.23 mL/minute). The lumen volumes determined
      with FPA and cast measurements demonstrated excellent correlation and can be
      related to each other by V(FPA) = 0.95V(C) - 0.01 (r = 0.997; standard error of
      estimate = 0.01 mL). CONCLUSIONS: The proposed automated method for accurate
      determination of coronary blood flow and lumen volume can supplement visual
      evaluation of coronary anatomy with quantitative physiologic data. This automated
      technique potentially offers a clinically feasible method of quantifying coronary
      blood flow and lumen volume in conjunction with routine cardiac catheterization.

PMID- 16428055
TI  - In vivo hemoglobin and water concentrations, oxygen saturation, and scattering
      estimates from near-infrared breast tomography using spectral reconstruction.
AB  - RATIONALE AND OBJECTIVES: Near-infrared (NIR) imaging has its niche in
      quantifying and characterizing functional changes in tissue relating to
      vascularity and metabolic status. Here, NIR tomography was applied to study
      mammographically normal breast tissue in vivo by evaluating relationships between
      functional parameters so obtained to clinical representers in an effort to
      understand factors influencing tissue compositional changes. MATERIALS AND
      METHODS: A new spectral reconstruction method that is considered to provide the
      most accurate estimates of hemoglobin level, oxygen saturation, water fraction,
      scattering power, and amplitude was used to assess healthy breast tissue imaged
      in vivo by means of NIR tomography. The approach directly recovers functional
      parameters with inherent inclusion of spectral behavior enforced through the
      incorporation of a priori model assumptions. Sixty subjects were imaged by using
      a frequency-domain instrument followed by spectral image reconstruction and
      statistical analysis for significant correlations. RESULTS: The new analysis
      shows statistically significant inverse correlations between body mass index and
      breast total hemoglobin and water fractions. Water fraction also correlated
      inversely with age and separated certain categories of breast density. Average
      scatter power was indicative of breast radiographic density composition, whereas
      scatter amplitude varied inversely with breast diameter. Total hemoglobin
      correlated with water fraction, whereas water correlated with scatter power.
      CONCLUSION: The changes observed here are attributable to volume fraction
      alterations and provide some of the most comprehensive data on breast composition
      variations with demographic factors.

PMID- 16428056
TI  - Head-mounted versus remote eye tracking of radiologists searching for breast
      cancer: a comparison.
AB  - PURPOSE: We compared performance and visual search parameters of radiologists
      detecting masses on mammograms by using both a head-mounted (HDMT) and a remote
      (REM) eye tracker. MATERIALS AND METHODS: Five experienced radiologists read
      twice a case set of 20 one-view (medial-lateral oblique) mammograms, of which 12
      contained a malignant mass and eight were lesion-free. For each observer, one
      trial used an HDMT eye-tracking system and the other used an REM system. Trials
      were separated on average by 2 months. Time to hit the location of the mass,
      dwell, and number of fixations in the location of the mass were measured. The
      same parameters were measured on a per-trial basis to determine whether there
      were memory effects from the previous trial. RESULTS: Dwell times in the location
      of true-positive, false-positive, and false-negative results were significantly
      shorter (P < .05) using the HDMT (median, 0.395 seconds) than REM (median, 0.482
      seconds) systems, but the number of fixations in the location of the response was
      smaller using the REM system (median, 4.33 versus 5.0 for the HDMT). The observed
      differences did not seem to be caused by a memory effect. In addition, the
      relative lack of head mobility using the REM system caused observers to report
      neck strain. CONCLUSION: Overall, radiologists' visual search behavior was very
      similar using both types of eye-tracking device. However, because the REM system
      did not contain a magnetic head tracker, radiologists were allowed very limited
      head movements when using it, which made them uncomfortable during the
      experiment.

PMID- 16428057
TI  - Detectability decreases with off-normal viewing in medical liquid crystal
      displays.
AB  - RATIONALE AND OBJECTIVES: To quantify the reduction in detection performance of
      subtle signals at off-normal viewing directions in medical active-matrix liquid
      crystal displays (AMLCDs). MATERIALS AND METHODS: Fifty synthetic image pairs per
      viewing condition (a total of 350) were used in a two-alternative forced-choice
      experiment in which 11 trained observers viewed images at 0, 30, and 45 degrees
      from the display normal, along the diagonal axis of a 5 million pixel in-plane
      switching monochrome AMLCD. The images were generated using white-noise
      backgrounds. A Gaussian signal was added to the signal-present set with three
      different signal amplitudes (4, 8, and 12 gray levels in a 10-bit scale).
      RESULTS: The average percent correct achieved for a signal of 4 gray levels was
      79.6 (95% confidence intervals based on reader and case variability: 71.6-86.9),
      63.4 (CI 56.0-71.3), and 55.3 (CI 48.4-62.0), for 0, 30 and 45 degrees from the
      display normal, respectively. When the signal amplitude was increased by a factor
      of two, the performance was 76.9 and 57.0 for 30 and 45 degrees, respectively,
      and 95.3 and 85.3 when the amplitude was increased by a factor of three. The
      observers took on average about twice as long and as much as seven times as long
      to reach decisions in off-normal viewing. CONCLUSIONS: Off-normal viewing of
      diagnostic images in AMLCDs significantly reduces the detection of low-contrast
      abnormalities. Increased off-normal signal amplitudes were required to regain the
      detection performance measured for normal viewing. We observed this decrease in
      detection performance for off-normal viewing even when measured decision times
      were about twice as long as for normal viewing.

PMID- 16428058
TI  - Cerebral edema attenuated inversion recovery MR sequence in low magnetic field: a
      feasibility study.
AB  - RATIONALE AND OBJECTIVES: Minimally invasive neurosurgery requires methods to
      specify surgical boundaries of target tissue, such as brain tumors. This study
      investigated technical possibilities and clinical usefulness of adapting edema
      attenuated inversion recovery (EDAIR) pulse sequences to suppress magnetic
      resonance signal from cerebral edema in brain tumor patients. MATERIALS AND
      METHODS: A resistive 0.23-T magnetic resonance scanner with magnitude-encoded
      inversion recovery sequences was used. Twenty-eight separate scanning tests in 25
      neurosurgical brain tumor patients were performed on the day before surgery. An
      inversion recovery sequence with several inversion times between 150 and 2,200 ms
      was tested. The same sequences were also used intraoperatively and
      postoperatively. RESULTS: T(1) relaxation time of brain edema varied from case to
      case. An inversion recovery sequence with an inversion time of 400-800
      milliseconds attenuated brain edema and seemed to help in demarcating gross brain
      tumor for surgical resection. These features were helpful for the evaluation of
      resectable tumor tissue particularly using neuronavigation techniques.
      CONCLUSIONS: According to these preliminary findings, inversion recovery
      sequences supplement other imaging modalities and assist neurosurgeons in
      evaluating different surgical trajectories and in estimating brain tumor volume
      before craniotomy.

PMID- 16428059
TI  - White matter proton MR spectroscopy in children with isolated developmental
      delay: does it mean delayed myelination?
AB  - RATIONALE AND OBJECTIVES: Isolated developmental delay (IDD) is a common disorder
      in preschool and school-age children. Conventional magnetic resonance imaging
      (MRI) usually does not disclose abnormalities, but a myelination delay is
      suspected as causative or associated factor. N-acetyl-aspartate is a surrogate
      marker of neuronal integrity but also of axonal integrity. The goal of our study
      is to determine whether magnetic resonance spectroscopy (MRS) is able to detect
      alterations in the white matter supporting the hypothesis of delayed myelination
      in children with IDD and normal MRI. MATERIALS AND METHODS: In this cross
      sectional study, we enrolled 12 consecutive children meeting the criteria if IDD
      and aged between 3 and 12 years (mean 7.25 years) and 11 healthy children as
      control group (mean age 7.18, range 3-12 years) on whom we performed conventional
      MRI and MRS. We did not include children with abnormal MRI. Single voxel (8
      cm(3)) was placed in the white matter of the left centrum semiovale. The mode of
      acquisition was probe-p (PRESS technique) with a TR of 2500 milliseconds and a TE
      of 30 milliseconds. We measured the metabolite concentration of n-acetyl
      aspartate (NAA), choline (Ch), creatine (Cr) y myo-inositol (mI), and ratios of
      NAA, Ch, and mI to creatine. RESULTS: In children with IDD, we found a
      significant decrease of the following ratios: NAA/Cr (P < .016), NAA/Ch (P <
      .026), and NAA/mI (P < .023) in relation to controls. The mean NAA/Cr ratio in
      IDD children was 1.92 (SD 0.14), and in controls it was 2.09 (SD 0.14); t = 2.62,
      fd (freedom degrees) = 21, P < .016. No differences were seen in the remaining
      ratios. CONCLUSIONS: The lower NAA/Cr ratio in children with IDD in relation to
      controls may be a promising marker of this disorder and supports the hypothesis
      of delayed myelination. MRS can provide important information in children with
      neurodevelopmental disorders.

PMID- 16428060
TI  - Evaluation of the quality of radiology requisitions for intensive care unit
      patients.
AB  - RATIONALE AND OBJECTIVES: The study aim is to evaluate the quality of radiology
      requisitions for plain film radiographs on intensive care unit (ICU) patients.
      MATERIALS AND METHODS: Radiology requisitions for 58 patients in ICU units at our
      children's hospital and the corresponding original orders for the study, written
      in patients' charts, were obtained. We reviewed each of the resident's written
      chart orders for completeness and then directly compared the information on the
      radiology requisition with the actual order written in the patient's chart by the
      ward resident physician. RESULTS: In 10% of cases, no "written order" was found
      in the patient's medical record for the imaging study. Clinical indications for
      the study were provided by the resident in only 71% (41/58) of cases. The
      resident's name was missing in the chart in eight of 58 cases (14%). The
      resident's name was provided in 50 cases, but was legible in only 28 of 50 cases
      (56%). In 84% of cases, the resident failed to provide his or her pager number.
      For one patient, the incorrect study was ordered. In only 73% (30/41) of cases
      did the ward clerk exactly copy the clinical indication that was handwritten in
      the chart by the resident. In 21% of cases, no resident's name was provided as
      the ordering resident on the radiology requisition. Inadequate or incomplete
      clinical information was provided in 24% of cases. CONCLUSION: Our study
      identifies a large number of problems in the quality of our radiology
      requisitions. Improving the process has been approved by our hospital as a major
      quality improvement project for this year.

PMID- 16428061
TI  - A new method of evaluating the quality of radiology reports.
AB  - RATIONALE AND OBJECTIVES: The radiology report must provide the ordering
      physician relevant information in an understandable format. The objectives of
      this study were to develop and apply a method for the grading of the quality of
      radiology reports and to evaluate differences based on the reader's experience.
      This grading method permits evaluation of compliance with the American College of
      Radiology communication standards. MATERIALS AND METHODS: A total of 240
      intensive care unit admission chest radiograph reports were retrieved from our
      hospital database. These were graded for quality. Our grading system is based on
      the concept that a radiology report must provide information relevant to the
      patient's known clinical status and thus is important to the ordering clinician.
      The best grade for a report is IV and the minimum grade assigned is I. Results
      were further analyzed based on the experience of the reader. RESULTS: A total of
      436 grades from the 240 reports were generated: 374/436 (86%) grades were
      designated a III or IV, which we deemed as satisfactory reports. The scoring of
      the radiology reports evaluating the position of endotracheal tubes, catheters,
      and enteric feeding tubes scored significantly better than definitive diagnosis
      as the starting point on the clinical spectrum (P < .01). The scores from all
      other patients starting points on the clinical spectrum, when compared with one
      another, were nonsignificant. Using a one-way analysis of variance, when
      comparing reports based on the six different levels of reader experience, first
      year residents up to staff radiologists reports showed no significant difference
      (P = .78). CONCLUSIONS: Ideally, 100% of radiology reports should receive a grade
      III or IV. Our study showed that only 86% of the reports met this standard.

PMID- 16428062
TI  - Coverage of emergency after-hours ultrasound cases: survey of practices at U.S.
      Teaching hospitals.
AB  - RATIONALE AND OBJECTIVES: Diagnostic ultrasound examinations may be performed
      after-hours by physicians if technologists are not available or cases are
      complex. Our experience suggested there is wide variability in how ultrasound
      coverage is provided after-hours, which motivated us to conduct a formal survey
      of teaching programs around the country. METHODS: Four hundred five members of
      the Association of Program Directors in Radiology were contacted by e-mail and
      sent a link to a five-part questionnaire posted on the Web. Respondents were
      asked whether ultrasound cases after-hours are performed in their institutions by
      radiology residents, technologists on the premises after-hours, technologists on
      call, or some combination. Data on the type of program, number of beds in the
      primary hospital, number of residents in the program, and geographic location of
      the program were recorded. Responses were automatically written to a data file
      stored on a Web server and the imported into an Excel spreadsheet for data
      analysis. A chi(2) analysis was performed to assess associations among the
      variables and statistical significance. RESULTS: A total of 79 programs responded
      to the survey. Of those, 32% provided coverage with ultrasound technologists on
      call, 24% by ultrasound technologists on the premises, 13% provided combination
      coverage, and 10% provided coverage solely with residents on call. There was no
      association among number of residents in the program, location of the program, or
      type of program (university, community, or affiliated) and type of coverage
      provided. CONCLUSION: There is wide variability in methods for providing coverage
      of after-hours ultrasound cases. However, on-site or on-call coverage of
      emergency cases by technologists did not appear to depend significantly on
      program location, program type, or program size.

PMID- 16428063
TI  - Academic recognition of educational scholarship.
AB  - Educators in radiology have an essential role in promoting the development and
      education of future radiologists and in the continuing education of radiologists.
      The contributions of educators to the viability and growth of the specialty
      require equal legitimacy to research in academic recognition. Development of
      educators and documentation of educational activities are key elements in
      achieving academic status for scholarly activity.

PMID- 16428064
TI  - Variability of preoperatively determined hepatic volumes in potential living
      liver donors.
AB  - RATIONALE AND OBJECTIVES: The aim of the study is to evaluate variability in
      hepatic volumes during the preoperative period in potential liver donors.
      MATERIALS AND METHODS: Eight potential living liver donors underwent preoperative
      multirow-detector computed tomographic assessment of hepatic transplant volumes
      twice. Intraindividual delay between the two examinations range was 3-62 days
      (mean, 30.1 days). Liver volumes were determined in a blinded fashion by an
      experienced radiologist and a transplantation surgeon. Results were compared and
      correlated with time of data acquisition during the day. RESULTS: Interobserver
      variability for assessments of liver volumes range was 6-32 mL (mean, 16 mL).
      Intraindividually, the difference between the two volume assessments ranged
      between -103 and +45 mL (mean, -19 mL), corresponding to percentages of
      alteration between -7.5% and +3.2%. There was no statistical correlation evident
      concerning volume alterations and specific time of data acquisition. CONCLUSION:
      Neither time of data acquisition nor waiting period for the surgical procedure
      seems to affect the accuracy of liver volume calculation. Apparent volume
      variations likely are in the range of the method error of the applied technique.

PMID- 16428067
TI  - Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.
AB  - Botanical polysaccharides exhibit a number of beneficial therapeutic properties,
      and it is thought that the mechanisms involved in these effects are due to the
      modulation of innate immunity and, more specifically, macrophage function. In
      this review, we summarize our current state of understanding of the macrophage
      modulatory effects of botanical polysaccharides isolated from a wide array of
      different species of flora, including higher plants, mushrooms, lichens and
      algae. Overall, the primary effect of botanical polysaccharides is to enhance
      and/or activate macrophage immune responses, leading to immunomodulation, anti
      tumor activity, wound-healing and other therapeutic effects. Furthermore,
      botanical and microbial polysaccharides bind to common surface receptors and
      induce similar immunomodulatory responses in macrophages, suggesting that
      evolutionarily conserved polysaccharide structural features are shared between
      these organisms. Thus, the evaluation of botanical polysaccharides provides a
      unique opportunity for the discovery of novel therapeutic agents and adjuvants
      that exhibit beneficial immunomodulatory properties.

PMID- 16428068
TI  - Accelerative effect of a selective cyclooxygenase-2 inhibitor on Fas-mediated
      apoptosis in human neutrophils.
AB  - Inflammatory stimuli, such as cytokines, can induce cyclooxygenase-2 (COX-2)
      expression in neutrophils. Selective, anti-inflammatory COX-2 inhibitors have
      been developed for patients with acute inflammatory diseases. Recent work has
      shown that selective COX-2 inhibitors interfere with tumor cell growth. The
      purpose of this study was to examine the capability of selective COX-2 inhibitors
      on Fas-mediated apoptosis in cytokine-stimulated neutrophils. Tumor necrosis
      factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) enhanced prostaglandin E2 (PGE2) release through the induction of COX-2 in
      neutrophils. This effect was not seen with either interleukin (IL)-1beta or IL-8.
      TNF-alpha-and GM-CSF-induced PGE2 release was blocked by the addition of the
      selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide
      (NS-398; 1 microM). GM-CSF, IL-1beta and IL-8 suppressed Fas-mediated apoptosis
      in neutrophils; however, this effect was not seen with TNF-alpha. The anti
      apoptotic effect of cytokines on Fas-mediated neutrophil apoptosis was attenuated
      by the addition of NS-398 (100 microM). These results suggest that NS-398
      operates via two distinct mechanisms for regulating apoptosis and COX-2
      activation in neutrophils. This distinction is indicated by the difference in
      concentration of NS-398 required for acceleration of Fas-mediated neutrophil
      apoptosis, and the inhibition of PGE2 synthesis. Moreover, NS-398 suppressed the
      anti-apoptotic activity of IL-8 and IL-1beta, but did not induce COX-2;
      therefore, the pro-apoptotic mechanism of the selective COX-2 inhibitor may be
      unrelated to COX-2 activity. Thus, a selective COX-2 inhibitor may contribute to
      the reduction of acute inflammation through the enhancement of neutrophil
      apoptosis.

PMID- 16428069
TI  - CpG oligodinucleotides induce strong humoral and cellular responses to swine
      streptococcic septicemia vaccine in piglets in vivo.
AB  - Oligodinucleotides containing CpG motifs (CpG ODN) are strong adjuvants for
      immune responses, particularly in mice, but data on humoral and cellular immune
      responses in piglets are scarce. In this report, using the swine streptococcus as
      model bacteria, CpG ODN was used as immunoadjuvants to enhance the immune
      responses of the piglets to swine streptococcic septicemia killed vaccine (SSSK
      vaccine). The titre of specific antibodies to SSSK vaccine, the proliferation of
      lymphocytes, SSSK-specific interferon-gamma(IFN-gamma) and IL-6, the expression
      of major histocompatibility complex class II (MHC-II) and CD14 of peripheral
      blood mononuclear cells (PBMCs) were examined to identify the immune responses of
      the piglets. The results were found that the above-mentioned immune responses of
      the piglets with CpG ODN were significantly stronger than standard immunization
      protocols. All these data suggested that immunostimulatory CpG ODN was promising
      immune enhancers for vaccination against SSSK vaccine.

PMID- 16428070
TI  - Association of cytokine gene polymorphisms and the release of cytokines from
      peripheral blood mononuclear cells treated with methotrexate and dexamethasone.
AB  - Immunosuppressive drugs are widely used in the therapy of autoimmune disorders to
      suppress autoreactive T cells. The immune system is regulated by the release of
      cytokines. Cytokine are potent immunomodulatory molecules that act as mediators
      of inflammation and the immune response. Primarily secreted by T cell and
      macrophages, they influence cellular activation, differentiation, and function.
      Cytokine production is under genetic control. This is evidenced by the
      identification of polymorphism in cytokine gene regulatory regions that correlate
      with intra-individual variations in actual cytokine production. The aim of the
      study was to examine whether the individual differences in the polymorphic
      cytokine genes can lead to individual variation in release of cytokines after
      treatment with methotrexate and glucocorticosteroids. The study was carried out
      on mononuclear cells isolated from peripheral blood of 72 healthy subjects. The
      cells were activated with PHA and incubated with increasing concentrations of
      methotrexate (0.1-10 microM) and dexamethasone (0.01-1 microM). Levels of IL-2,
      IL-4, IL-6, IL-10, and TNFalpha in the culture supernatants were quantified by
      flow-cytometry using Th1/Th2 kit and correlated with cytokine gene polymorphisms.
      The increased concentrations of DEX resulted in comparable cytokine
      concentrations in cultures from subjects with low and high cytokine genotypes.
      Despite MTX treatment, the cytokine levels were significantly increased in
      individuals homozygous for the high producer allele. These results suggest that
      the cytokine gene variants may influence the efficacy of therapy with some
      immunosuppressive and anti-inflammatory drugs.

PMID- 16428072
TI  - Glycyrrhizin derivative inhibits eotaxin 1 production via STAT6 in human lung
      fibroblasts.
AB  - We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate
      TNFalpha- and IL-4-induced eotaxin 1 production by the human fetal lung
      fibroblast line HFL-1 at protein or mRNA levels. In particular, the GL derivative
      hetero-30-OH-GL (3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D
      glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol) showed marked inhibition of
      eotaxin 1 production with less cytotoxicity than 18beta-GL. To identify the
      molecular mechanism of this effect, we focused on the inhibition of the
      transcriptional factors NF-kappaB and signal transducer and activator of
      transcription 6 (STAT6), which regulate eotaxin 1 gene activation. STAT6
      phosphorylation and translocation of phospho-STAT6 from cytosol to nuclei were
      slightly inhibited by 18beta-GL and significantly inhibited by hetero-30-OH-GL.
      While IkappaBalpha degradation and translocation of NF-kappaB p65 to nuclei were
      not significantly affected by either compound, the stability of eotaxin-1 mRNA
      was decreased with hetero-30-OH-GL. In addition, eotaxin 1 promoter activity was
      markedly inhibited by hetero-30-OH-GL. Electrophoretic mobility shift assay
      (EMSA) confirmed these results. Thus, hetero-30-OH-GL significantly inhibited
      eotaxin 1 expression by the selective inhibition of IL-4 signal transduction as
      well as by enhanced mRNA degradation.

PMID- 16428071
TI  - Budesonide, but not tacrolimus, affects the immune functions of normal human
      keratinocytes.
AB  - Topical immunosuppressant therapy is widely used in the treatment of inflammatory
      skin diseases such as psoriasis and atopic dermatitis. Besides its beneficial
      therapeutic effects, application of topical anti-inflammatory drugs may render
      the epidermis more vulnerable to invading pathogens by suppressing innate immune
      responses in keratinocytes, such as cytokine production and Toll-like receptor
      (TLR) expression. In order to evaluate and compare the immunosuppressive effects
      of different immunosuppressant drugs on keratinocytes, we treated
      lipopolysaccharide (LPS)-stimulated and -unstimulated normal human keratinocytes
      with the synthetic corticosteroid budesonide and the macrolide tacrolimus. The
      expressions of the pattern recognition receptors (PRRs) TLR2 and TLR4 were
      measured by quantitative RT-PCR, pro-inflammatory cytokines IL-1alpha, IL-8 and
      TNF-alpha were monitored by quantitative RT-PCR and by ELISA, and alterations in
      TLR2 protein level were measured by flow cytometry. Budesonide had a suppressive
      effect on both constitutive and LPS-induced IL-8 gene expression. The amount of
      TNF-alpha mRNA was diminished in unstimulated keratinocytes, while TLR2 mRNA
      expression was markedly enhanced both in unstimulated and LPS-treated cells after
      incubation with budesonide. This increase in TLR2 mRNA expression was also
      detectable at the protein level in LPS-stimulated cells. Tacrolimus had no effect
      on any of the examined genes. Budesonide, but not tacrolimus, significantly
      inhibited the NF-kappaB-dependent luciferase reporter activity in HaCaT cells
      after induction with LPS or TNF-alpha. Although tacrolimus and budesonide are
      both effective treatments in some inflammatory skin diseases, the data provided
      here imply differences in local therapeutic and adverse effects of these two
      topical immunosuppressants.

PMID- 16428073
TI  - In vitro and in vivo effects of mercuric chloride on thymic endocrine activity,
      NK and NKT cell cytotoxicity, cytokine profiles (IL-2, IFN-gamma, IL-6): role of
      the nitric oxide-L-arginine pathway.
AB  - Mercury (Hg2+) affects cell-mediated immunity, including thymulin production.
      Thymulin, a zinc-dependent thymic hormone synthesized by thymic epithelial cells
      (TECs), is involved in NK cell cytotoxicity and Th1 cytokine production (IL-2 and
      IFN-gamma), which in turn affect both NKT and classic NK spleen cell
      cytotoxicity. High doses of Hg2+ induce an inflammatory status, increased
      production of IL-6 and consequent Th1/Th2 imbalance as well as cell-mediated
      immune depression. The mechanisms by which Hg+ affects the cell-mediated immune
      response are still unclear. The nitric oxide (NO) pathway may be implicated. The
      aim of this work was to further explore its noxious role in innate and adaptive
      immunity and to study the possible role played by the NO pathway. Young Balb/c
      mice treated in vivo for 1 month with 1.0 mg HgCl2/kg b.w. showed low thymulin
      activity, depressed NO production (as measured by nitrite and nitrate plasma
      levels), impaired classic NK spleen cell cytotoxicity, decreased Th1 (IL-2 and
      IFN-gamma) cytokine profiles, and increased IL-6 production. In vitro, 10(-6) M
      of HgCl2 inhibited active thymulin kinetics, TEC proliferation, NKT cell
      cytotoxicity and Th1 cytokine production, whereas IL-6 increased. L-arginine
      restored thymulin activity, TEC proliferation, NKT cytotoxicity, cytokine
      profiles and nitrite and nitrate plasma levels both in vivo and in vitro. Since L
      arginine is the substrate for NO production, it may compensate for the cell
      mediated immune defect induced by HgCl2, via the arginine-NO-pathway. L-arginine
      is also able to reduce glomerular kidney IgG antibodies deposits induced by
      higher dose of HgCl2 administration.

PMID- 16428074
TI  - Beer down-regulates activated peripheral blood mononuclear cells in vitro.
AB  - Moderate consumption of alcoholic beverages is suggested to reduce cardiovascular
      risk. Within this context, most attention is drawn to antioxidant ingredients of
      wine, but also beer was found to be beneficial. Potential effects of three
      different types of beer including alcohol-free beer were investigated using
      freshly isolated human peripheral blood mononuclear cells stimulated with the
      mitogen phytohaemagglutinin in vitro. Neopterin production and tryptophan
      degradation were monitored in culture supernatants to determine effects of test
      substances on immunobiochemical pathways induced by interferon-gamma. In a
      subgroup of experiments also production of interferon-gamma was measured.
      Compared to unstimulated cells, phytohaemagglutinin increased production of
      neopterin and also triggered the degradation of tryptophan (all p < 0.01). All
      types of beer (2-4% dilution) were found to counteract these stimulation-induced
      effects and significant reduction of neopterin formation and tryptophan
      degradation was observed (p < 0.01). Data demonstrate that beer reduces
      production of neopterin and degradation of tryptophan, both these biochemical
      pathways are induced during cell-mediated immune response. Data suggest that the
      immunosuppressive capacity of beer may relate to its anti-inflammatory nature.

PMID- 16428075
TI  - Dexamethasone, colchicine and iodine-lithium-alpha-dextrin act differentially on
      the oxidative burst and endotoxin tolerance induction in vitro in patients with
      Behcet's disease.
AB  - Pro-inflammatory activation of innate immune cells, such as macrophages, and
      neutrophils in patients with Behcet's disease (BD) results in increased
      production of reactive oxygen species and enhanced adhesion to endothelial cells
      due to increased expression of adhesion receptors. We investigated the influence
      of dexamethasone (DEX), colchicine (Col), and iodine-lithium-alpha-dextrin
      (ILalphaD), during BD, on the respiratory burst of whole blood neutrophils and
      monocytes, CD11a/CD18 surface expression, monocyte endotoxin tolerance and
      cytokine synthesis in vitro. In BD patients we observed an increase of the
      spontaneous, N-formyl-Met-Leu-Phe- and LPS-induced respiratory burst of monocytes
      and neutrophils as well as up-regulation of neutrophil CD11a/CD18 surface
      expression. DEX, Col and ILalphaD in vitro differentially affected the stimulus
      dependent oxidative burst of BD and caused the down-regulation of CD11a/CD18
      surface expression in neutrophils but not monocytes. LPS homologous tolerance
      induction is not altered in BD. However, DEX and Col increased tolerance to LPS
      induced TNF-alpha synthesis. ILalphaD down-regulated N-formyl-Met-Leu-Phe- and
      LPS-induced oxidative burst and CD14 receptor expression and increased monocyte
      cross-tolerance to LPS. DEX induced LPS-tolerance by restoring the ratio of INF
      gamma and IL-4 production, while Col caused a dramatic increase in IL-4 synthesis
      by monocytes. DEX, Col and ILalphaD may limit the overwhelming inflammation by
      differentially affecting the monocyte activation program, shifting them from
      ''classically" into "alternatively'' activated monocytes and may have important
      implications for the treatment of BD.

PMID- 16428076
TI  - Physalins B, F and G, seco-steroids purified from Physalis angulata L., inhibit
      lymphocyte function and allogeneic transplant rejection.
AB  - Physalis angulata is a solanaceae widely used in folk medicine in various
      tropical countries in the world. We have previously described that seco-steroids
      (physalins) purified from P. angulata are potent inhibitors of macrophage
      activation, blocking the production of pro-inflammatory cytokines and LPS-induced
      lethality. Herein we investigated the immunomodulatory activities of these
      substances in lymphocyte proliferation and cytokine production and in
      transplantation. The addition of physalins B, F or G to concanavalin A-activated
      splenocyte cultures induced a concentration-dependent inhibition of
      proliferation. Physalin B also inhibited IL-2 production by Con A-activated
      spleen cells. The addition of 2 mug/ml physalin B to mixed lymphocyte reaction
      (MLR) caused a 100% inhibition of proliferation. More importantly, treatment of
      mice with physalin B, F or G prevented the rejection of allogeneic heterotopic
      heart transplant. Our results demonstrate the suppressive activity of physalins
      B, F and G in lymphocyte function and indicate the potential use of physalins as
      immunosuppressive agents for treatments of pathologies in which inhibition of
      immune responses is desired.

PMID- 16428077
TI  - Renal and macrophage aminopeptidase activities in cyclosporin-treated mice.
AB  - Cyclosporin, an immunosuppressive drug, is known to affect macrophage and to
      exert a nephrotoxic effect. Aminopeptidases play important roles for renal and
      macrophage functions. In this work, we attempt to test the hypothesis that the
      aminopeptidases participate within macrophage and renal effects induced by
      cyclosporin. Macrophage and renal aminopeptidase activities of cyclosporin
      treated and control mice were evaluated, as well as renal caspase 3 activity,
      hematocrit, urinary protein and plasma osmolality, creatinine and uric acid
      concentrations. Cyclosporin treatment increased caspase 3 activity, hematocrit
      and osmolality, while urinary protein, creatinine and uric acid were unaltered.
      Soluble and particulate aminopeptidases in resident and elicited macrophages were
      unaffected by cyclosporin. The treatment with cyclosporin increased neutral,
      basic, cystyl, prolyl imino and pyroglutamyl soluble aminopeptidase activities in
      the renal cortex. Acid and basic soluble aminopeptidase activities increased in
      the renal medulla. Increased levels of particulate form in the cortex were
      detected for acid and pyroglutamyl aminopeptidase activities. Cyclosporin
      increased cortical soluble while decreased medullar particulate prolyl dipeptidyl
      aminopeptidase IV activity. With the exception of prolyl dipeptidyl
      aminopeptidase IV, particulate aminopeptidase activities returned to levels
      similar to controls after fifteen days of cyclosporin withdrawal, and soluble
      aminopeptidase activities did not regress. Our data indicate that the adopted
      regimen of cyclosporin treatment produced mild renal impairment with consistent
      changes on the levels of renal but not macrophage aminopeptidase activities. The
      obtained profiles of macrophage and renal aminopeptidase activities should be
      considered into the elaboration of new potential strategies for preventing
      nephrotoxicity during the treatment with cyclosporin.

PMID- 16428078
TI  - Brazilein, an important immunosuppressive component from Caesalpinia sappan L.
AB  - Caesalpinia sappan has been shown to have interesting immunosuppressive
      properties. Its heartwood has long been used in Chinese medicines for treating a
      variety of immune-mediated pathology and inflammatory disease. The purpose of
      this work was to evaluate the immunocompetence effects of brazilein on mice
      lymphocytes in vitro and in vivo. The results showed that brazilein and
      Caesalpinia sappan ethanol extract (SME) could distinctly inhibit the
      proliferation of T lymphocyte stimulated by Concanavalin A (Con A) and the
      proliferation of B lymphocyte stimulated by lipopolysaccharides (LPS), and
      brazilein could suppress mice humoral immune response by plaque forming cell
      (PFC) test. In addition, immune organs (thymus and spleen) in mice treated with
      brazilein were notably atrophied and weight loss in vivo (intraperitoneal
      injection, i.p.). In attempting to investigate the mechanisms of the
      immunosuppressive activity of brazilein, we discovered that brazilein can induce
      apoptosis in mice spleen lymphocytes by flow cytometry analysis and DNA
      fragmentation assay, which may be one of the pathways that brazilein inhibited
      immunocompetence of mice lymphocytes.

PMID- 16428079
TI  - Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT
      signaling pathway: protection by black tea.
AB  - Down-regulation of cell-mediated immune functions occurring at late stages of
      cancer may be related to the thymic involution since thymus is the major site of
      T cell maturation, proliferation, and differentiation. We found that in Ehrlich's
      ascites carcinoma (EAC)-bearing mice there was profound depletion of CD4+ and
      CD8+ cells in peripheral blood with severely damaged thymus on 21st day of tumor
      inoculation. However, treatment with black tea at an antitumor dose of 2.5%
      significantly reduced such depletion and protected the thymus considerably from
      tumor onslaught. A search for the underlying mechanism revealed EAC-induced IL
      7Ralpha down-regulation, inhibition of JAK3 and STAT5 phosphorylation, and
      decrease in Bcl-2/Bax ratio in thymocytes that finally led to thymocyte apoptosis
      in one hand and T cell maturation block on the other. Interestingly, black tea
      treatment prevented IL-7Ralpha down-regulation and protected the signaling
      cascade through JAK-STAT thereby inhibiting tumor-induced thymic apoptosis and
      ensuring proper functioning of this organ in tumor-bearing host.

PMID- 16428080
TI  - Prevention of early renal injury by mycophenolate mofetil and its mechanism in
      experimental diabetes.
AB  - Previously it was shown that treatment with mycophenolate mofetil (MMF)
      attenuated renal inflammation and glomerular injury in a model of diabetes.
      However, the mechanism involved in the renoprotective effects of MMF in
      experimental diabetes has not been clearly delineated. Diabetes was induced by
      injection of streptozotocin (STZ) after uninephrectomy. Diabetic animals received
      no treatment or treatment with MMF (10 mg/kg once daily by gastric gavage) for 8
      weeks, non-diabetic rats served as controls. Level of malondialdehyde (MDA) in
      renal tissue and urine as well as the activity of antioxidant enzymes (AOE) in
      renal tissue was determined. Renal injury was evaluated. Immunohistochemistry for
      ED-1 macrophages marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte
      chemoattractant protein-1 (MCP-1) was performed. Expression of transforming
      growth factor (TGF)-beta1 protein was determined by Western blotting analysis.
      Treatment with MMF had no effect on blood glucose level, but did prevent
      increased urinary albumin excretion and glomerular damage in diabetic rats.
      Oxidative stress was reduced by MMF treatment, as indicated by a reduction in MDA
      level in renal tissue and urine. Activity of AOE such as glutathione peroxidase
      (GSH-PX) was markedly elevated while superoxide dismutase (SOD) and catalase
      (CAT) were not changed by MMF treatment. In diabetic animals receiving no
      treatment, there were increases in ED-1-positive cells, ICAM-1 expression and MCP
      1 expression in glomeruli and tubulointerstitium, which were effectively
      suppressed by MMF treatment. Western blotting analysis showed that the expression
      of TGF-beta1 protein was increased by 1.92-fold in renal tissue in diabetic rats,
      and MMF treatment significantly reduced the increased expression of TGF-beta1
      protein by 45%. Our data suggest that MMF treatment ameliorates early renal
      injury via the inhibition of oxidative stress and overexpression of ICAM-1, MCP-1
      and TGF-beta1 in renal tissue in diabetic rats.

PMID- 16428081
TI  - Synergism in immunotoxicological effects due to repeated combined administration
      of arsenic and lead in mice.
AB  - Arsenic and lead are considered potent human hazards because of their neoplastic
      outcomes; increasing epidemiologic evidence indicates a link between heavy metal
      exposure and health risk. Since health risks of singly administered metals are
      well-established, in the present study we determined whether simultaneous
      repeated multimetal (arsenic + lead) exposure influences the development of
      immunotoxicity in mice exposed (in vivo) to lead acetate (10 mg/kg b.w.) and
      sodium arsenite (0.5 mg/kg b.w.) simultaneously. We report that in vivo
      multimetal exposure alters cell morphology, inhibits cell adhesion, nitric oxide
      release, intracellular killing ability, chemotactic migration, myeloperoxidase
      release, bacterial clearance from blood and spleen and increases DNA
      fragmentation. On measuring bacterial density in blood and spleen after 0, 24, 48
      and 72 h post infection (with Staphylococcus aureus MC524) in control and
      multimetal treated groups, bacterial load showed delayed clearance from blood and
      spleen in the multimetal exposed group. We also found that in vivo exposure to
      the multimetal caused a decrease in cell adhesion, indicated by a fall in
      absorbance at 570 nm with respect to control. Exposure to multimetal led to
      morphological changes in macrophages, since more deformed cells were obtained in
      repeated combined exposure to arsenic and lead compared to control. Nitric oxide,
      which has a potent microbicidal activity in macrophages, was found to be released
      in fewer amounts in the multimetal exposed group from that of control group. It
      was observed that the viability of bacteria gradually decreased in control
      macrophage with time, whereas, in macrophages of multimetal exposed mice, the
      viability of S. aureus gradually increased. Chemotactic migration of splenic
      macrophages significantly decreased in the multimetal exposed group from that of
      control. Lysosomal enzyme release from splenic macrophages decreased upon
      simultaneous exposure to arsenic and lead, as is evident from the decrease in
      myeloperoxidase release in multimetal group from that in control. That the
      structural integrity of splenic macrophages is decreased in the multimetal
      exposed group is also evident from the enhanced percentage of DNA fragmentation
      after multimetal exposure, suggesting apoptotic death of splenic macrophage.
      Intracellular viable bacteria in the splenic macrophage from multimetal exposed
      group was 89.16 +/- 3.54% while that from control group was 49.19 +/- 1.16%,
      whereas single metal exposed groups showed a bacterial viability of 69.6 +/-
      2.45% and 71.71 +/- 1.89% in arsenic and lead treated groups respectively. What
      is essentially noteworthy from the observed results is that lead and arsenic
      causes a greater immunotoxic effect when administered together as multimetal than
      when singly administered. Simultaneous exposure to lead and arsenic appears to be
      additive as is further established from the isobologram constructed by plotting
      the concentration of arsenic against the concentration of lead at which effect
      (in this case myeloperoxidase release) remained constant, a convex line showing
      synergism was demonstrated. The present study reports a definite synergistic
      trend of immunotoxicity during simultaneous exposure to arsenic and lead, that
      is, a multimetal challenge, as compared to the effects of independent exposure to
      them.

PMID- 16428082
TI  - Involvement of phosphatidylinositol-3 kinase-Akt and nuclear factor kappa-B
      pathways in the effect of frutalin on human lymphocyte.
AB  - The mechanisms involved in the mitogenic effect of lectins are not fully
      understood and are thought to involve a cascade of intracellular signals related
      to T cell receptor activation. This study shows that frutalin, the alpha-D
      galactose-binding lectin from Artocarpus incisa seeds, is a potent mitogenic
      activator of human lymphocytes. This effect is inhibited by D-galactose and PI3K
      inhibitors, and is accompanied by an increase in IL-2 receptor expression and by
      a PI3K-dependent IL-2 gene expression and IL-2 protein synthesis. Frutalin also
      induces Akt-phosphorylation and activates NF-kappaB, inducing its translocation
      from the cytosol to the nucleus. Both effects are blocked in the presence of D
      galactose or by PI3K inhibitors. In summary, frutalin, interacting with alpha-D
      galactose, activates signaling pathways related to TCR, and thereby triggers
      PI3K/Akt and NF-kappaB pathway, which modulates T cell proliferation, IL-2
      synthesis and IL-2R expression. Frutalin might be a useful tool to study
      intracellular mechanisms following T cell activation that link upstream signaling
      pathways to downstream events.

PMID- 16428083
TI  - Activation of murine peritoneal macrophages by sulfated exopolysaccharide from
      marine microalga Gyrodinium impudicum (strain KG03): involvement of the NF-kappa
      B and JNK pathway.
AB  - This study examined the ability of microalgal sulfated exopolysaccharide (MSE)
      from marine microalga Gyrodinium impudicum (strain KG03) to induce secretory and
      cellular responses in murine peritoneal macrophages. The cytotoxicity induced by
      preincubating tumor cells with MSE was demonstrated to be concentration
      dependent. The MSE-induced tumoricidal activity was partially abrogated by a NO
      inhibitor, whereas the anti-TNF-alpha and anti-IFN-alpha/beta antibodies as well
      as the scavengers of reactive oxygen intermediates had no effect. In addition,
      supernatants from murine peritoneal macrophages treated with MSE contained
      nitrite and their iNOS enzymatic activity was significantly increased. Therefore,
      the tumoricidal activity induced by MSE appeared to be mediated by the production
      of NO. Treating the macrophages with a JNK inhibitor (SP600125) partially blocked
      the tumoricidal activation and NO production induced by MSE, whereas inhibitors
      of the other kinases did not have an inhibitory effect. These results suggest
      that MSE induces NO production via the JNK dependent pathway. Furthermore,
      electrophoretic mobility shift assay analyses revealed that the MSE treatment
      induced the activation of the NF-kappaB transcription factor. Overall, these
      results indicate that the tumoricidal activity induced by MSE is mainly due to NO
      production, and the activation of macrophage by MSE is mediated probably via the
      NF-kappaB and JNK pathway.

PMID- 16428084
TI  - Role of H1 receptors in histamine-mediated up-regulation of STAT4
      phosphorylation.
AB  - Histamine shifts TH1/TH2 cytokine balance from TH1 to TH2 cytokines and regulates
      the function of lymphocytes after binding to histamine receptors. The
      phosphorylation of STAT factors and the translocation to the nucleus are
      important steps in the regulation of TH1/TH2 cytokine balance. This study was
      designed to investigate the effects of histamine on the phosphorylation of STAT4.
      C57BL/6 splenocytes were isolated and treated with histamine (10(-4) to 10(-9) M)
      after activation with either PMA (phorbol 12 myristate 13-acetate) plus ionomycin
      or IL-12. The phosphorylated STAT4 levels were analyzed by Western Blot Analysis.
      Unstimulated splenocytes expressed both STAT4 and phosphorylated STAT4. However,
      phosphorylated STAT4 gradually declined within 24 h. Histamine increased the
      phosphorylation of STAT4 at lower concentrations (10(-6) to 10(-9) M), and had no
      effect at higher concentrations (10(-4) and 10(-5) M) after the cells were
      stimulated with PMA + ionomycin. Histamine did not affect IL-12-induced
      phosphorylation of STAT4. To characterize the histamine receptor subtypes
      involved in the up-regulation of STAT4 phosphorylation, various H1, H2 and H3/H4
      receptor antagonists and/or agonists were employed. H1 receptor agonist
      (betahistine), but not H2 receptor agonist (amthamine), induced phosphorylation
      of STAT4. H1 receptor antagonist (pyrilamine) inhibited histamine-mediated
      phosphorylation of STAT4. However, H2 receptor antagonist (ranitidine) and H3/H4
      receptor antagonist (thioperamide) did not alter this effect. Tyrosine kinase
      inhibitor (tyrphostin) failed to block histamine-mediated phosphorylation of
      STAT4. These observations suggest that histamine up-regulated the phosphorylation
      of STAT4 via H1 receptors, and that the Ca2+-PKC pathway, but not the tyrosine
      kinase pathway, was involved in this effect.

PMID- 16428085
TI  - Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites
      tumor cells is inhibited by Glycyrrhiza glabra.
AB  - Blood vessel plays a crucial role in solid tumor development. It has been
      suggested that blocking of angiogenesis and the action of the cytokine VEGF could
      be possible in cancer therapy. In a screen for naturally occurring angiogenic
      inhibitors, we have identified an extract from the roots of Glycyrrhiza glabra,
      which has potent antiangiogenic and antitumor activity. The aqueous extract
      inhibits the in vivo and in vitro proliferation of Ehrlich ascites tumor cells.
      The angioinhibitory activity of G. glabra was confirmed by its inhibition of
      angiogenesis in in vivo assays, peritoneal and chorioallantoic membrane assay.
      Reduction in the levels of the cytokine VEGF and microvessel density count in the
      peritoneum of mice treated with G. glabra indicated that the plant extract
      decreased VEGF production and the cytokine induced neovascularization. Our
      results suggest that the extract from the roots of G. glabra may be a potential
      supplemental source for cancer therapy.

PMID- 16428087
TI  - Membrane lipid microdomains differentially regulate intracellular signaling
      events in human neutrophils.

PMID- 16428086
TI  - Monitoring of immune responses to a herbal immuno-modulator in patients with
      advanced colorectal cancer.
AB  - Many herbal medicines are widely used as immuno-modulators in Asian countries.
      Ganoderma lucidum (Lingzhi) is one of the most commonly used herbs in Asia and
      preclinical studies have established that the polysaccharide fractions of G.
      lucidum have potent immuno-modulating effects. However, clinical evidence for
      this is scanty. The present open-labeled study aimed to evaluate the effects of
      G. lucidum polysaccharides on selected immune functions in patients with advanced
      colorectal cancer. Forty-seven patients were enrolled and treated with oral G.
      lucidum at 5.4 g/day for 12 weeks. Selected immune parameters were monitored
      using various immunological methods throughout the study. In 41 assessable cancer
      patients, treatment with G. lucidum tended to increase mitogenic reactivity to
      phytohemagglutinin, counts of CD3, CD4, CD8 and CD56 lymphocytes, plasma
      concentrations of interleukin (IL)-2, IL-6 and interferon (IFN)-gamma, and NK
      activity, whereas plasma concentrations of IL-1 and tumor necrosis factor (TNF)
      alpha were decreased. For all of these parameters, no statistical significance
      was observed when a comparison was conducted between baseline and those values
      after a 12-week treatment with G. lucidum. The changes of IL-1 were correlated
      with those for IL-6, IFN-gamma, CD3, CD4, CD8 and NK activity (p<0.05) and IL-2
      changes were correlated with those for IL-6, CD8 and NK activity. The results
      indicate that G. lucidum may have potential immuno-modulating effect in patients
      with advanced colorectal cancer. Further studies are needed to explore the
      benefits and safety of G. lucidum in cancer patients.

PMID- 16428089
TI  - Operative management of small bowel fistulae associated with open abdomen.
AB  - BACKGROUND: Gastrointestinal fistulae associated with open abdomen are serious
      complications following trauma or other major abdominal surgery. Management is
      extremely difficult and the mortality is still high in spite of modern medical
      advances. Patients who survive initial physiological and metabolic derangements
      require operative closure of the fistula, which is technically demanding and
      poorly described in the literature. METHODS: A retrospective study of patients
      with small bowel fistulae associated with open abdomen was performed. Only
      patients who were stabilized sufficiently to undergo surgical closure of the
      fistula were enrolled in the study. The operative techniques comprised three
      important steps: exploratory laparotomy and resection of small bowel fistulae
      with end-to-end anastomosis; bridging the abdominal wall defect with a sheet of
      polyglycolic acid mesh; and covering the mesh with bilateral bipedicle anterior
      abdominal skin flaps. RESULTS: Eight patients were included in the study. The
      number of operations before surgical closure of the fistula ranged from one to
      six (mean, 3.6). The time from first operation to surgery for fistula closure
      ranged from 2.5 to 7.5 months (mean, 4.4 months). Three patients had recurrent
      fistula, and one died (mortality, 12.5%). Hospital stay ranged from 101 to 311
      days (mean, 187 days). CONCLUSION: We present a method of closure of small bowel
      fistulae associated with open abdomen and hope that this will provide surgeons
      encountering such complications with a good alternative for surgical management.

PMID- 16428090
TI  - Eventration of the diaphragm.
AB  - OBJECTIVE: Eventration of the diaphragm (ED) is defined as the abnormal elevation
      of the diaphragm. Although asymptomatic ED may be amenable to conservative
      treatment, symptomatic ED in children, either congenital or acquired, may require
      surgical treatment. This study evaluated the results of diaphragmatic plication
      in children with unilateral ED. METHODS: Fifteen patients who had undergone
      diaphragmatic plication for ED between 1997 and 2003 were evaluated
      retrospectively. The diagnosis of ED was established by routine chest radiographs
      and fluoroscopy. Patients who failed to respond to nonoperative treatment were
      referred for surgery. Nine patients underwent diaphragmatic fluoroscopy 1-5 years
      following plication to assess function. RESULTS: Indications for diaphragmatic
      plication were respiratory symptoms such as tachypnoea, dyspnoea, recurrent
      pneumonia and failure to thrive. In 14 patients, the position of the diaphragm
      was normal after plication, but the diaphragm was elevated without symptoms in
      one patient during postoperative follow-up. The motion of the diaphragm was
      investigated in nine patients. Fluoroscopic studies showed that the operated
      hemidiaphragm was immobile and there was no paradoxical motion. No return of
      symptoms was found during follow-up. CONCLUSION: ED is the abnormal elevation of
      the diaphragm as a result of paralysis or aplasia of the muscular fibres. The
      abnormally elevated diaphragm may compress the ipsilateral lung, and with
      respiratory effort the mediastinum may shift towards the normal side. Therefore,
      diaphragmatic plication is performed to restore normal pulmonary parenchymal
      volume by replacing the diaphragm in its normal location. After plication, there
      was immediate remission of symptoms in most patients and decreasing symptoms were
      observed for a year in others. During follow-up, the location of the diaphragm
      was normal and no paradoxical movement was observed. Relapse of symptoms was not
      noted in patients with immobile diaphragms.

PMID- 16428091
TI  - Management of civilian extraperitoneal rectal injuries.
AB  - OBJECTIVE: The mortality and morbidity of rectal injuries are highly
      unsatisfactory. We retrospectively reviewed our experience with rectal injuries
      to draw some practical guidelines for management of such injuries. METHODS: The
      medical records of all patients diagnosed at our hospitals with full-thickness
      rectal injuries between 1994 and 2003 were retrospectively reviewed. RESULTS:
      Full-thickness rectal injuries were identified in 23 patients; 19 patients had
      extraperitoneal injuries and four had both intra- and extraperitoneal injuries.
      The mean age was 33.5 years (range, 5-73 years). The mechanism of injury was
      penetrating in 11 patients, blunt in six, impalement in three and iatrogenic in
      three. Injuries were closed primarily in 17 patients, with variable combinations
      of adjunct procedures. Eight patients were treated without colostomy. Drainage
      and rectal washout were performed in 11 and six patients, respectively. Overall,
      11 patients developed complications, including eight wound infections and five
      pelvic septic complications related to the rectal injury. Four of the five pelvic
      septic complications and all three deaths occurred in patients with shock, at
      least two associated-organ injuries and more than 6 hours' delay in treatment.
      CONCLUSION: Rectal injuries are serious additive mortality and morbidity factors
      in multi-injured patients. Regardless of treatment modality, wound infection is
      associated with shock at presentation and more than 6 hours' delay in treatment.

PMID- 16428092
TI  - Oesophageal replacement in children with indolent stricture of the oesophagus.
AB  - OBJECTIVE: To evaluate the indications for and results of oesophageal replacement
      for acquired oesophageal stricture in children. METHODS: This was a descriptive
      interventional study. Between 1987 and 2003, patients who had peptic or corrosive
      stricture were included in the study. Age and gender were analysed and any
      history of ingestion of caustic agents or untreated reflux was noted. Types of
      symptoms such as progressive dysphagia to solids and liquids and extent of
      respiratory infections were evaluated. Nutritional deprivation was also measured.
      Success or failure of dilatation at the time of endoscopy was taken into account.
      The criterion for oesophageal replacement was recurrence of stricture within 3
      weeks of the previous dilatation. Patients were prepared with general supportive
      care. Feeding gastrostomy was performed in 12 patients who were severely
      malnourished. No patients underwent oesophagectomy of the strictured oesophagus.
      Short- and long-term complications were recorded. RESULTS: Of the 54 patients, 34
      were male and 20 were female. Colonic conduit and reverse gastric tube were used
      in 27 patients each. Three patients had leak and were treated conservatively. Six
      patients developed anastomotic stricture but benefited remarkably from periodic
      dilatation and, in the long-term, remained symptom-free. Results were generally
      very gratifying. CONCLUSION: Most patients who require oesophageal conduit do
      well and catch up with their growth and development.

PMID- 16428093
TI  - Primary anterior sagittal anorectoplasty for rectovestibular fistula.
AB  - OBJECTIVE: To reduce the morbidity and suffering of patients with rectovestibular
      fistula (RVF) and to lessen the cost of the staged management protocol. METHODS:
      A prospective study was carried out in the Department of Paediatric Surgery of
      Dhaka Shishu (Children) Hospital, Bangladesh, from January 2002 to February 2004.
      Twenty-three patients underwent primary anterior sagittal anorectoplasty (ASARP)
      for RVF, of whom 18 had congenital and five had acquired RVF. Patient age ranged
      from 15 days to 5 years. The diagnosis was made from history, clinical
      examination and ultrasonography. RESULTS: The mean operating time was 90 minutes.
      There were no major perioperative complications. Three patients developed partial
      wound disruption in the postoperative period. All patients started oral feeding
      on the 4th postoperative day and the mean hospital stay was 6 days. The average
      bowel movements per day were 3-5 motions, without any oral therapy or enema. Two
      patients had occasional perineal soiling. All patients are being followed-up and
      the early postoperative results seem acceptable. CONCLUSION: Primary ASARP is a
      good procedure for RVF as it is quick and cost-effective and requires no
      colostomy, laparotomy or laparoscopy.

PMID- 16428094
TI  - Single scrotal incision orchiopexy for palpable undescended testis.
AB  - OBJECTIVE: To prospectively evaluate the Bianchi single scrotal incision
      technique for orchiopexy in boys with palpable undescended testis. METHODS: A
      total of 35 orchiopexies were performed in 28 patients. The patent processus
      vaginalis was dissected and cut high without ligation, while in Bianchi's
      original procedure, the patent processus vaginalis is dissected up to the
      external inguinal canal, ligated high and divided. Testicular size and position
      were assessed at 2 and 6 weeks and 6 months. RESULTS: The single incision
      technique was successful in all cases. All testes were satisfactorily positioned
      in the scrotum. All testes showed good anatomical and cosmetic results at 6-month
      follow-up. CONCLUSION: Single scrotal incision orchiopexy without ligation of the
      patent processus vaginalis has proved to be simple, safe and effective in
      selected cases compared with the standard two-incision approach in the treatment
      of palpable undescended testis.

PMID- 16428095
TI  - Incidental inguinal hernias on laparoscopy.
AB  - OBJECTIVE: Laparoscopic examination of the contralateral inguinal ring has been
      advocated to exclude contralateral hernia in young children. We used the size of
      the open internal ring and the depth of the patent processus vaginalis as a
      parameter to decide whether laparoscopic herniotomy was indicated. METHODS:
      Records of all laparoscopic procedures in children performed in a large tertiary
      care hospital over a 2.5-year period were retrospectively analysed. RESULTS:
      Laparoscopy in 346 children revealed the presence of an incidental asymptomatic
      patent processus vaginalis in 47 cases. Of these, 38 were present as a
      contralateral hernia among 171 laparoscopies for inguinal hernias. CONCLUSION:
      The presence of an incidentally detected, asymptomatic but significant-sized open
      internal ring is not uncommon. The authors recommend that a 1-cm diameter and a 2
      cm depth of open internal ring be taken as a significant indication for
      herniotomy. The authors also emphasize that a reported incidence of contralateral
      patent processus vaginalis of up to 56.2% justifies the procedure of laparoscopic
      herniotomy in all children.

PMID- 16428096
TI  - Pulmonary endocrine cells in hypoplastic lungs due to foetal urinary tract
      obstruction: a microscopic immunohistochemical study.
AB  - METHODS: We performed a urinary tract obstruction (UTO) surgical procedure at 93
      107 days' gestation in lambs to investigate the relationship between pulmonary
      hypoplasia and the appearance of pulmonary endocrine cells by quantitative
      analysis of respiratory tract cells using light microscopic immunohistochemistry.
      RESULTS: UTO produced a significant reduction in lung weight, lung/body weight
      ratio, air capacity, air capacity/body weight ratio (p < 0.01) and radial
      alveolar count (p < 0.05), which indicated the presence of lung hypoplasia. These
      foetuses also showed a significant increase in the number of neuron-specific
      enolase (NSE)-positive pulmonary endocrine cells, expressed as the number of NSE
      positive cells per bronchus (p < 0.01) or bronchiole (p < 0.05), the number of
      NSE-positive cells per unit perimeter of bronchus or bronchiole (p < 0.01), and
      the number of NSE-positive cells per unit bronchial or bronchiolar surface area
      (p < 0.01). CONCLUSION: These results suggest that UTO significantly retards and
      modifies the structural growth and functional development of pulmonary endocrine
      cells in NSE expression. We speculate that pulmonary endocrine cells and their
      mediators may play a role in the problems associated with UTO during intrauterine
      life.

PMID- 16428097
TI  - Shock wave lithotripsy for uric acid stones.
AB  - OBJECTIVE: To report our experience of extracorporeal shock wave lithotripsy
      (SWL) for patients with uric acid stones. METHODS: From December 1987 to December
      2003, a total of 443 patients with uric acid stones in the kidney or ureter
      accepted SWL using ultrasound-guided lithotripters together with alkali therapy.
      Among them, 168 patients with an average stone burden of 9.1 mm were treated
      using an EDAP LT-01 piezoelectric lithotripter. The other patients, with an
      average stone burden of 9.6 mm, were treated using a Dornier Compact S
      electromagnetic lithotripter. RESULTS: The average duration of treatment using
      the EDAP LT-01 device was 52.1 minutes with a pulse frequency of 1.25-2.5 shocks
      per second at 100% power. The average treatment parameters on the Dornier Compact
      S device were 3,196 shocks at 14.8 kV. For the EDAP LT-01, the 3-month stone-free
      rate was 86.4%, with a retreatment rate of 24.2%. For the Dornier Compact S, the
      3-month stone-free rate was 90.3%, with a retreatment rate of 29.0%. Auxiliary
      therapy with the push-back technique was needed in 0.45% of patients with upper
      ureteral stones that could not be localized using ultrasound. The treatment
      results were best for stones smaller than 20 mm. No anaesthesia was required for
      any patient. CONCLUSION: SWL with ultrasound localization for uric acid stones is
      safe and effective. The combination of SWL with urine alkalization may further
      improve the stone-free rate.

PMID- 16428098
TI  - Renal cell carcinoma of 4 cm or less: an appraisal of its clinical presentation
      and contemporary surgical management.
AB  - OBJECTIVE: Greater availability and utilization of modern radiological imaging
      modalities have resulted in an increase in the incidental discovery of renal cell
      carcinoma. Such tumours tend to be smaller than their symptomatic counterparts
      and may potentially be adequately treated using nephron-sparing surgery. METHODS:
      A retrospective review of all patients who were diagnosed with renal cell
      carcinoma of 4 cm or less between January 1990 and December 2001 was conducted to
      review clinical presentation, surgical management and survival. RESULTS: The
      cohort comprised 102 patients who underwent surgery, of 402 patients diagnosed
      with renal cell carcinoma over the study period. Sixty-eight patients (67%) had
      tumours detected incidentally. Thirty patients (29%) were managed with partial
      nephrectomy and 72 (71%) with radical nephrectomy. The median tumour size was 3.0
      cm (range, 1.5-4.0 cm). Overall, median follow-up was 60 months (range, 1-148
      months). Overall 5-year survival for patients who underwent partial nephrectomy
      and radical nephrectomy was 96.6% and 85.8%, respectively. Cancer-specific 5-year
      survival was 100%. CONCLUSION: A significant proportion of patients had
      incidental diagnosis of small renal cell carcinoma. Local control may be achieved
      with either radical or partial nephrectomy, with excellent survival expected.

PMID- 16428099
TI  - Spontaneous transmural migration of surgical sponges.
AB  - Postoperative retained surgical sponges or other foreign bodies are usually
      underreported. Radio-opaque materials are usually detected on follow-up
      radiological investigations, but radiolucent materials such as sponges create
      diagnostic problems and clinically mimic various abdominal pathologies.
      Introduction of spiral computed tomography, magnetic resonance imaging and
      dedicated ultrasonography has enabled clinicians to find these foreign bodies at
      the earliest opportunity to avoid disastrous complications. Spontaneous
      transmural migration and expulsion per rectum of more than one sponge without
      sequelae is also possible. We report one such interesting case.

PMID- 16428100
TI  - Chylous ascites after anterior resection for rectal carcinoma: a rare but
      significant incident.
AB  - Chylous ascites specifically after anterior resection for rectal cancer has not
      been documented in the literature thus far. All previously reported postoperative
      chylous ascites developed in other types of malignancies and were diagnosed
      within a few days of surgery. However, the patient we report had symptoms 2 years
      after surgery. Intraoperatively, chylous ascites was found with multiple lymph
      node metastasis in the small bowel mesentery and retroperitoneal region. The
      rarity of chylous ascites after anterior resection in rectal carcinoma is
      documented and discussed.

PMID- 16428101
TI  - Abdominal tuberculosis mimicking metastasis in a patient with carcinoma of the
      oesophagus.
AB  - Oesophageal carcinoma typically manifests as ulcerative growth. Cases of
      oesophageal tuberculosis mimicking carcinoma of the oesophagus have been reported
      and create considerable diagnostic difficulty. Abdominal tuberculosis, however,
      is an uncommon extrapulmonary manifestation of tuberculosis. Here, we report a
      case of abdominal tuberculosis in a patient with squamous carcinoma of the
      oesophagus.

PMID- 16428102
TI  - Retroperitoneal lymphangioma.
AB  - Lymphangiomas are rare cystic tumours that may present as cystic masses in the
      retroperitoneum. Retroperitoneal lymphangiomas account for approximately 1% of
      all lymphangiomas. Confusion with other cystic tumours of the retroperitoneum
      including those arising from the liver, kidney and pancreas is common. A case of
      a retroperitoneal cystic lymphangioma occurring in a 41-year-old woman raising
      interesting diagnostic and management issues is reported. The patient presented
      with vague abdominal pain and persistent nausea. Radiological imaging
      demonstrated a large multiloculated thin-walled cyst involving the upper
      retroperitoneum. Surgical resection was complete, revealing a benign cavernous
      lymphangioma. The patient made a complete recovery and was disease-free 30 months
      postoperatively.

PMID- 16428103
TI  - Endoscopic drainage of empyema of the gallbladder through a concurrent
      cholecystoduodenal fistula.
AB  - The duodenum is the most common site of cholecystoenteric fistulation resulting
      from cholecystitis or empyema of the gallbladder. This rare condition is usually
      only diagnosed intraoperatively and managed incidentally. This paper presents the
      endoscopic diagnosis of a case of cholecystoduodenal fistula arising from the
      late presentation of empyema of the gallbladder and its subsequent drainage
      through the fistula. As far as we can determine, this is the only reported case
      of opportunistic drainage of an empyema of the gallbladder through a concurrent
      cholecystoduodenal fistula.

PMID- 16428104
TI  - Paediatric Intra-abdominal Inflammatory Myofibroblastic Tumour.
AB  - Inflammatory myofibroblastic tumour is a rare solid tumour mimicking malignancy
      with locally aggressive growth and recurrence even after complete resection. We
      report the case of a 10-year-old girl with an intra-abdominal inflammatory
      myofibroblastic tumour. This clinical and pathological entity should be
      differentiated from other malignant sarcomatous lesions when encountered
      intraoperatively. It is almost impossible to differentiate inflammatory
      myofibroblastic tumour from other malignancies preoperatively; the diagnosis is
      often confirmed by careful microscopic examination or immunohistochemical markers
      after surgical resection. Total excision of the tumour with life-time follow-up
      is needed because of the risk of recurrence.

PMID- 16428105
TI  - Relationship between maximum daily temperature and mortality of broiler chickens
      during transport and lairage.
AB  - 1. Based on records of all (n = 59 171 843) broiler chickens slaughtered over
      three years at one processing plant, the overall mortality of birds in transit
      was 0.126%. 2. There was a pronounced seasonal effect with increased mortality in
      the summer months, particularly June, July and August. Mortality increased when
      the maximum daily temperature (measured in the shade) rose above about 17 degrees
      C at the start of the summer. 3. Between 17.0 and 19.9 degrees C, mortality was
      30% higher than at lower temperatures. Between 20.0 and 22.9 degrees C it
      increased 2.6-fold, and at temperatures of above 23 degrees C 6.6-fold. There was
      no evidence of birds dying from hypothermia at very low ambient temperatures
      (down to -1 degrees C). 4. The implication from the results is that above a
      maximum daily temperature of 17 degrees C steps may need to be taken to
      ameliorate the damaging effects of transport on bird welfare.

PMID- 16428106
TI  - The ostrich (Struthio camelus) blastoderm and embryo development following
      storage of eggs at various temperatures.
AB  - 1. The gross morphology of blastoderms in fresh unstored ostrich eggs and in eggs
      subjected to different regimen of storage and incubation was studied. Then the
      effects of storage duration of eggs (1, 2 and 3 weeks) and storage temperature
      (15, 20 and 25 degrees C) on blastoderm and embryo development were
      investigated.2. Only incubation following overnight storage at 18 degrees C
      advanced blastoderm development (1.5-fold increase in diameter) to a stage
      comparable to hypoblast. 3. Storage of eggs at 15 or 20 degrees C did not affect
      blastoderm stage and size whereas, at 25 degrees C, the blastoderm doubled in
      size and appeared to have advanced to a primitive streak stage. Embryo
      development was reduced after 2 weeks of storage regardless of the storage
      temperature. 4. After oviposition and during pre-incubation storage the ostrich
      blastoderm develops progressively over time in a temperature-dependent manner
      towards the hypoblast stage and beyond but the viability of the blastoderm and
      embryo development is seriously compromised by 2 weeks of storage.

PMID- 16428107
TI  - Quantitative analysis of embryonic kidney impairment by confocal microscopy and
      stereology: effect of 1,2-dibromoethane in the chick mesonephros.
AB  - 1. Chick embryos in ovo were treated with a teratogenic dose of 1,2-dibromoethane
      (DBE) on embryonic day (ED) 3. On ED 6 and 10, histological sections of whole
      embryos were prepared for confocal microscopy. In parallel, mesonephroi of 10-d
      old embryos were dissected for in situ staining with acridine orange (AO), a
      fluorescence probe for lysosomes. 2. DBE impaired differentiation of renal
      vessels which manifested as a delay in rearrangement of primitive renal vascular
      architecture on ED 6 and a significant reduction of the mesonephric
      vascularisation on ED 10. This was accompanied by delayed functional maturation
      of embryonic kidney, as suggested by staining with AO. 3. Renal vessels appeared
      to be more susceptible to DBE than tubules. Unequal growth of these renal
      components might be a cause of DBE-induced spatial disorganisation of tubular
      apparatus. 4. Nephrotoxic effects of DBE during the embryonic period are
      associated primarily with damage to the renal blood supply. 5. Confocal
      microscopy, stereological methods and three-dimensional reconstruction of
      developing tissues are useful tools to investigate pathogenic processes during
      embryonic development.

PMID- 16428108
TI  - Microflora of two different types of poultry litter.
AB  - 1. The microbiological composition of litter (straw and wood shavings) was
      sampled, prior to placing 1-d-old chicks, during housing of the birds and after
      depopulation. Two independent trials were conducted. 2. The total aerobic plate
      count (APC) was determined and the predominant microflora of the samples was
      identified using flow charts. 3. Before chick placement, the APC of wood shavings
      (about 4.0 log/g) was lower than the APC of straw (about log 7.5/g). With
      stocking, in both types of litter the APC increased to about log 9.76/g straw
      litter and log 9.89/g wood shavings, respectively. After depopulation, the APC
      remained high (> log 9 in both types of litter) within the period of observation.
      4. From both experiments, 1981 isolates were collected and identified, most of
      them were Gram-positive. During stocking the birds, the number of Gram-positive
      isolates (in particular Gram-positive irregular rods and Micrococcaceae)
      increased; after depopulation it stayed at that high value, whereas the number of
      Gram-negative isolates remained low. In both types of litter the isolates were
      obtained in a comparable proportion.

PMID- 16428109
TI  - Carry-over effects of dietary yeast RNA as a source of nucleotides on lymphoid
      organs and immune responses in Leghorn-type chickens.
AB  - 1. The carry-over effects of supplementing Leghorn-type chickens with yeast RNA
      as a dietary source of nucleotides for 4 weeks on growth, lymphoid organ weights
      and immune responses were assessed in a 12-week study. 2. A commercial starter
      feed supplemented with 0 (control), 5 (LR) or 10 (HR) g yeast RNA/kg was offered
      to 1-d-old male ISA Brown chicks for 4 weeks, and then all birds were given a
      commercial pullet grower feed for another 8 weeks. Growth performance, antibody
      responses to sheep red blood cells (SRBC) and cutaneous reactivity of toe webs to
      phytohaemagglutinin (PHA)-M were measured at 4-week intervals. 3. Growth rates,
      feed intake and feed efficiency were not affected by dietary yeast RNA during the
      supplementary period, but birds previously offered the HR diet grew faster than
      control birds during weeks 4 to 8.4. LR-fed birds had a higher spleen weight
      relative to body weight (BW) than control birds at week 4, but this effect was
      not detected at other times. 5. Serum primary antibody levels against SRBC were
      not affected by dietary yeast RNA at any time. 6. The toe-web PHA response was
      significantly higher at week 8 in control birds than in birds previously given
      the LR diet, although no difference among dietary treatments was observed at
      other times. 7. It is concluded that the addition of yeast RNA as a source of
      nucleotides to a commercial diet selectively stimulated the development of the
      spleen in young birds, but this effect did not persist into a later stage of the
      bird's life.

PMID- 16428110
TI  - Cytokine responses in broiler lines that differ in susceptibility to
      malabsorption syndrome.
AB  - 1. Based on earlier studies it was hypothesised that there is an immunological
      basis for the differences in susceptibility to malabsorption syndrome (MAS). A
      study was conducted to investigate base-line and MAS-induced cytokine levels in
      the intestine of broilers that differ in MAS susceptibility. 2. The transcription
      of cytokine mRNA in the intestine was quantified using a real-time polymerase
      chain reaction (PCR) method. At different time points after disease induction the
      intestines of broilers were investigated for expression of interleukin (IL)-2, IL
      6, IL-8, IL-18 and interferon (IFN)-gamma. Age-matched non-MAS-induced chickens
      served as controls. 3. Control chickens from a MAS-resistant line had higher
      concentrations of mRNA for IL-2, IL-6, IL-18 and IFN-gamma in the small intestine
      while no difference between the lines was found for IL-8. After induction of MAS
      the relative amounts of IL-2, IL-6, IL-8 and IFN-gamma mRNA increased more in the
      intestines of the susceptible line than in the gut of the resistant line. 4. We
      suggest that differences in cytokine mRNA in the base-line situation and in MAS
      induced conditions indicate a difference in immune response regulation in the two
      broiler lines. This difference in response could lead to the difference in
      susceptibility to MAS.

PMID- 16428111
TI  - Rheological characteristics of fresh and frozen PSE, normal and DFD chicken
      breast meat.
AB  - 1. Textural and rheological differences among broiler breast meat ranging from
      pale, soft and exudative (PSE) to dark, firm and dry (DFD) in their fresh and
      frozen (and thawed) forms were investigated. 2. The PSE meat showed significantly
      higher lightness values and lower pH and water holding capacity values than
      normal and DFD meats; DFD meat was also significantly different from normal meat.
      3. During cooking, PSE meat lost significantly more liquid and produced a softer
      gel than normal or DFD meats; texture profile analysis parameters were lower for
      the PSE meat. 4. The storage modulus values (G', rigidity of elastic response of
      the gelling material) showed that DFD meat produced a more rigid gel during
      cooking (especially above 54 degrees C) and later during cooling (back to 30
      degrees C) compared with the PSE meat. 5. Freezing resulted in a trend of lower
      G' values before, during and after cooking. The results indicated that meat
      proteins were damaged during freezing and PSE meat was more severely affected, or
      that more protein denaturation occurred in the PSE meat.

PMID- 16428112
TI  - Eggshell characteristics and penetration by Salmonella enterica serovar
      Enteritidis through the production period of a layer flock.
AB  - 1. Egg weight, shell thickness, number of pores, cuticle deposition and ability
      of Salmonella enterica serovar Enteritidis (SE) to penetrate the shell were
      determined for eggs from one layer flock through the entire production period. 2.
      Penetration was assessed by filling the eggs with a selective medium that allowed
      visualising Salmonella growth on the inside of the shell and membrane complex.
      After inoculation of each shell with on average 2.59 log cfu, the eggs were
      stored for up to 20 d at 20 degrees C and 60% relative humidity (RH). 3. On
      average 38.7% of the eggshells became penetrated. Mostly penetration occurred on
      d 3. Although it affected all shell characteristics studied, hen age did not
      significantly influence eggshell penetration. 4. No correlations were observed
      between any of the shell characteristics studied and the ability of SE to
      penetrate the shell. The growth of SE on the shell is of major importance because
      shell contamination at 20 d of storage and SE penetration were highly correlated.

PMID- 16428113
TI  - Effect of dietary saffron (Crocus sativus L.) on the oxidative stability of egg
      yolk.
AB  - 1. The effects of dietary inclusion of red stigmas of Greek saffron (Crocus
      sativus L.) on the oxidative stability of shell eggs and liquid yolks were
      investigated and compared with those of dietary a-tocopherol. 2. Ninety-six
      Lohmann laying hens, 38 weeks old, distributed into 4 groups with 4 replicates
      each, were given either a control diet, diets enriched with 10 (SAF10) or 20
      (SAF20) mg/kg saffron, or a diet enriched with 200 mg/kg a-tocopheryl acetate
      (VE200). 3. Following 6 weeks of feeding, eggs were collected and the rate of
      lipid oxidation was determined in refrigerated stored shell eggs, as well as in
      yolks adjusted to a pH of 6.2 or 4.2 and stored in the presence of light. 4. The
      results showed that the extent of lipid oxidation in shell eggs, as measured by
      malondialdehyde (MDA) formation, differed between dietary treatments, but did not
      change with storage time. In stored shell eggs, MDA levels differed between
      dietary treatments at all time points. 5. Yolks from the control group adjusted
      to pH 6.2 gave MDA values higher than those of the SAF10 group, which in turn
      were higher than those of the SAF20 group, a finding suggesting that saffron
      exerted a dose-dependent antioxidative activity. The VE200 group gave lower MDA
      values than the other groups at all time points. The oxidation profile of yolks
      at pH 4.2 showed a similar pattern but the rate of oxidation was greater.

PMID- 16428114
TI  - Effects of Lactobacilli and lactose on Salmonella typhimurium colonisation and
      microbial fermentation in the crop of the young turkey.
AB  - 1. Three experiments were performed to examine the effects of Lactobacilli and
      lactose on microbial fermentation and Salmonella enterica serovar Typhimurium
      colonisation in the crop of the young turkey. 2. The following carboxylic acids
      were detected in the crop ingesta: formic, acetic, butyric, lactic, valeric,
      caproic, oxalic, phenyl acetic, succinic and fumaric; propionic, isobutyric and
      isovaleric acids were not detectable. 3. At the beginning of the night, there
      were considerable quantities of ingesta in the crop of young turkeys. During the
      scotophase, there were progressive reductions in the contents and pH. Moreover,
      there were linear increases in the concentration of lactic, valeric and caproic
      acids (by approximately 7-fold over 8 h). Much smaller changes in crop pH were
      observed in the study where dietary treatments of Lactobacilli were not included.
      4. Chronic addition of lactose or Lactobacilli to the diet exerted modest effects
      on the carboxylic acid concentration in the crop contents but did not
      consistently influence colonisation of the crop by Salmonella enterica serovar
      Typhimurium. 5. Young turkeys confine eating to the hours of illumination
      (photophase) with a peak in consumption prior to the subjective dusk.

PMID- 16428115
TI  - The effect of conditioning temperature and exogenous xylanase addition on the
      viscosity of wheat-based diets and the performance of broiler chickens.
AB  - 1. A total of 1920 Ross broiler chicks were used in a 6 treatment by 8 replicate
      growth study to investigate the effect of conditioning temperature and exogenous
      xylanase addition on diet characteristics and bird performance. 2. Increasing
      conditioning temperature from 80 to 90 degrees C increased the viscosity of the
      diets by approximately 6 mPa.s and reduced body weight gain of the broiler
      chickens by 7%. 3. Furthermore, there was a significant interaction between
      temperature and the addition of exogenous xylanase, with a proportionately
      greater positive response to added xylanase in the diets that were pelleted at
      higher temperatures. 4. Addition of exogenous xylanase also increased the
      proportion of soluble arabinoxylan in the feed and reduced dietary viscosity,
      which is likely to be related to the degree of polymerisation of the soluble
      carbohydrate. 5. These results suggest that conditioning temperature should be
      considered as a factor when attempting to predict the response of broilers to
      added xylanase, especially when high-viscosity or 'low-quality' wheat is being
      used. 6. It can be concluded that pelleting wheat-based diets above 80 degrees C
      can compromise bird performance and that, if higher temperatures are to be
      employed, the use of exogenous xylanase is critical to maintain productivity.

PMID- 16428116
TI  - The maintenance requirement of domestic drakes.
AB  - 1. Mature domestic drakes of 7 genotypes, ranging in live weight from 1.1 to 5.1
      kg, were each given a daily allowance of feed just below the level of recorded ad
      libitum intake. 2. House temperature was maintained at 26 degrees C for 16 weeks
      and then at 10 degrees C for a further 8 weeks. 3. Under these conditions, live
      weight quickly adjusted to the level of feed supplied and then remained stable.
      4. Regression of metabolisable energy intake on live weight (W) yielded estimates
      of maintenance requirement of 583 kJ/kgW(0.75).d at 10 degrees C and 523
      kJ/kgW(0.75).d at 26 degrees C.

PMID- 16428117
TI  - Effects of artificial supplemental light on the reproductive season of geese kept
      in open houses.
AB  - 1. New lighting programmes were designed to change the pattern of goose
      reproduction, based on the response of predictable avian photoperiodic
      stimulation. The objective of this study was to evaluate the efficiency of a long
      photoperiod of 20L on shifting goose reproduction to the non-breeding season in
      an open housing system. 2. Eighty mature White Roman geese were randomly
      allocated into 4 groups (male:female = 1:4). The supplemental lighting programmes
      with a daily photoperiod of 20 h were initiated on 22 November and withdrawn when
      90% of geese were moulting in the treatment groups. Artificial light intensities
      of 220, 120 and 20 lux were provided to experimental groups A, B and C,
      respectively. In contrast, the geese in control group D were kept under natural
      lighting conditions throughout this study. 3. The annual reproductive curves of
      all the experimental groups consisted of two separate laying periods. The first
      period was induced by the supplemental lighting programme while the second was
      induced by the naturally increasing photoperiod in this subtropical region. The
      first laying period of the experimental groups occurred in the breeding season,
      and the second was relocated to the non-breeding season. 4. The supplemental
      lighting could shift the laying periods of geese to the non-breeding season and
      had no significant effect on annual reproductive performance. The supplemental
      light programmes described here were able to manipulate the reproductive season
      of geese reared in open houses, which would be of practical value.

PMID- 16428119
TI  - The 'bioidentical/bioequivalent' hormone scam.

PMID- 16428120
TI  - Development of a revised version of the Women's Health Questionnaire.
AB  - OBJECTIVES: The Women's Health Questionnaire (WHQ) includes 36 items assessing
      nine domains of physical and emotional experiences of mid-aged women. The primary
      aim of the current research was to examine the psychometric properties of the WHQ
      across linguistic versions in view of the increased need for reliable health
      related quality of life (HRQL) measures in multinational studies. METHODS: In
      this paper, we examine the hypothesized structure of the questionnaire in a UK
      sample, to develop and verify a revised model to be used in multicenter,
      international studies. RESULTS AND CONCLUSIONS: Content analysis and evaluation
      of missing data led to exclusion of 'Menstrual symptoms' and 'Sexual behavior'
      domains, retaining these as optional modules of the core questionnaire.
      Additionally, item 13 was excluded because it does not investigate the same
      concepts as other domains and the deletion of five additional items appeared to
      improve the questionnaire's factor structure. The revised WHQ comprises 23 items,
      investigating six domains. The cross-sectional psychometric properties of the 23
      item WHQ were good and better than those of the 36-item version. The 23-item WHQ
      was assessed with multinational data, to evaluate cross-cultural equivalence of
      linguistically adapted versions. In addition, its reproducibility and
      responsiveness need to be documented.

PMID- 16428121
TI  - Mid-age health in women from the Indian subcontinent (MAHWIS): general health and
      the experience of menopause in women.
AB  - OBJECTIVES: First, to examine the experience of menopause and quality of life in
      a migrated Asian population from the Indian subcontinent living in Birmingham,
      UK, and, second, to compare their experience with a matched sample of Caucasian
      women living in the same geographical area and also with a sample of Asian women
      with similar socioeconomic background living in Delhi, India. METHODS: In this
      cross-sectional study of 153 peri- and postmenopausal women aged 45-55 years, 52
      Asian women originating from the Indian subcontinent living in Birmingham (UKA,
      mean age 51.4 years), 51 Caucasian women (UKC, mean age 52.3 years) and 50 Asian
      women living in Delhi, India (DEL, mean age 49.72 years) were interviewed to
      collect information about their lifestyle, general health, menopause experience
      and help-seeking behavior. The Women's Health Questionnaire and the Menopause
      Representation Questionnaire (both translated and linguistically validated in
      Hindi) were used to examine the prevalence of physical and emotional symptoms and
      the extent to which these were attributed to the menopause. RESULTS: The two
      Asian groups (UKA, DEL) reported poorer health and generally more physical and
      emotional symptoms than the UKC group. However, for menopausal symptoms (hot
      flushes and night sweats) there was a different pattern; the DEL group reported
      significantly fewer symptoms compared to the UKA and UKC groups (hot flushes: UKC
      60.8%, UKA 75%, DEL 32% (p < 0.001); night sweats: UKC 50%, UKA 56.9%, DEL 24% (p
      = 0.002)). The prevalence of vaginal dryness was highest in the UKA group and
      lowest in the DEL group (UKC 21.6%, UKA 38.2%, DEL 7.3% (p = 0.005)). The number
      of symptoms attributed to menopause was significantly lower in the DEL group (9.3
      +/- 7.8) compared to the two UK groups (UKC 18.9 +/- 7.4, UKA 19.8 +/- 10.7), but
      the UKA women tended to attribute some physical symptoms to the menopause such as
      breathlessness, weight gain and stiff joints that might have other causes.
      CONCLUSIONS: The UK Asian women's experience of the menopause is more similar to
      the Caucasian women in the UK than that of the women in Delhi. However, Asian
      women living in the UK and the Indian subcontinent shared the experience of poor
      health and reports of more physical and emotional symptoms in general. The
      possible reasons for these differences are discussed.

PMID- 16428122
TI  - Menopausal symptoms in a hospital-based sample of women in southern Thailand.
AB  - OBJECTIVE: To evaluate menopausal symptoms and quality of life in middle-aged
      women. STUDY DESIGN: Hospital-based, cross-sectional study. METHODS: A survey was
      conducted among 270 women aged 45-65 years who attended the gynecological and
      menopause clinic, Songklanagarind Hospital. We used the MENQOL questionnaire as
      the instrument. RESULTS: The average age at menopause of the postmenopausal women
      was 48.7 years (range 40-57 years). The prevalences of the classical menopausal
      symptoms--hot flushes, night sweats, and vaginal dryness--in the women aged 45-65
      years were 36.8%, 20.8 and 55.3%, respectively. The three most prevalent symptoms
      in perimenopause were aching in muscles and joints, experiencing poor memory, and
      change in sexual desire. Within the four domains (vasomotor, psychological,
      physical, and sexual symptoms), more suffering was reported in the perimenopausal
      and postmenopausal subjects than in the premenopausal subjects (p < 0.001).
      CONCLUSIONS: Peri- and postmenopausal women had a significant decrease in quality
      of life compared to premenopausal women.

PMID- 16428123
TI  - Chinese women's symptoms: relation to menopause, age and related attitudes.
AB  - OBJECTIVES: The China Study of Midlife Women (CSMW) aimed to determine in mid
      life Chinese women, first, the frequency of various symptoms often included in
      studies of menopause or the climacteric, second, attitudes toward menopause and
      aging, and, third, the relationship between symptoms and menopausal status,
      chronological age and attitudes. METHODS: A questionnaire was administered via
      face-to-face interview to a general population sample of 399 Chinese women living
      in two communities in northern China. RESULTS: The Chinese women displayed a low
      to moderate frequency of reporting 21 symptoms across vasomotor, vaginal, sleep
      related, cognitive, emotional and somatic categories. Their attitudes toward
      menopause and aging tended to be more positive, neutral or ambivalent, as opposed
      to negative. There was a small, statistically significant association between six
      symptoms and menopausal status, four symptoms and chronological age, and 11
      symptoms and negative attitudes toward menopause and aging. CONCLUSIONS: Across
      the measures utilized in this study, Chinese women's symptom reporting is more
      strongly associated with their attitudes towards menopause and aging than their
      menopausal status or chronological age. More research is needed on cross
      cultural, cross-ethnic and individual variation in women's interpretations of
      statements often included in mid-life attitudinal scales.

PMID- 16428124
TI  - Metabolic syndrome throughout the menopausal transition: influence of age and
      menopausal status.
AB  - OBJECTIVE: To assess the relationship between the main components of both the
      metabolic syndrome and insulin resistance and menopausal status in the menopausal
      transition. METHODS: A total of 124 healthy women were divided into four groups
      according to their menstrual status: the first group consisted of 35 women in
      menopausal transition with menstrual bleeding (MTM) and with cycles between 35
      and 80 days; the second group was composed of 29 women in menopausal transition
      with 3-6 months of amenorrhea (MTA). The third group consisted of 31
      postmenopausal women (PostM) and the fourth group of 29 premenopausal women
      (PreM) with regular cycles. The metabolic syndrome was evaluated following the
      ATP III criteria. Evaluation of insulin resistance was made through the HOMA,
      QUICKI and McAuley indices and the triglycerides/high density lipoprotein (HDL)
      cholesterol ratio. RESULTS: The triglycerides/HDL cholesterol ratio increased in
      MTM, MTA and PostM women in comparison with PreM women. A slight decrease in the
      QUIKI index (p = 0.06) and a decrease in the McAuley index (p < 0.001) were
      observed in MTM, MTA and PostM women in comparison to PreM women. The relative
      frequencies of metabolic syndrome in the four groups were: PreM, 0%; MTM, 20%;
      MTA, 21%; and PostM, 22% (p = 0.0001). The most frequent markers of the metabolic
      syndrome were increased waist circumference, low HDL cholesterol levels and
      hypertension. Linear regression between menopausal status and metabolic syndrome
      was lost when age was added to the model. CONCLUSIONS: The frequency of metabolic
      syndrome increased from the time of the menopausal transition to the
      postmenopause. Abdominal obesity was the most frequent feature observed.
      Nevertheless, aging erased the effect of the menopause on the metabolic syndrome.
      In order to prevent cardiovascular disease, the metabolic syndrome must be
      evaluated from the time of the menopausal transition.

PMID- 16428125
TI  - Menopausal symptoms in women treated for breast cancer: the prevalence and
      severity of symptoms and their perceived effects on quality of life.
AB  - OBJECTIVES: To determine, first, the prevalence and severity of various symptoms
      related to estrogen deficiency in women within a few years of receiving treatment
      for breast cancer, second, how women perceive the effects of these symptoms on
      their quality of life and, third, what measures have been taken to relieve
      vasomotor symptoms. METHODS: Two hundred women (aged 29-65 years) who had
      received treatment for breast cancer within the last 5 years were included in
      this cross-sectional survey. Information was collected about their breast cancer
      treatment, menopausal symptoms (Menopausal Rating Scale), the perceived effects
      of menopausal symptoms on their and their partner's quality of life and any
      treatments they were receiving for hot flushes. RESULTS: All but one woman
      reported at least one symptom related to the menopause (95.9% vasomotor; 83.3%
      psychological; 89.7% somatic). Current treatment with tamoxifen or previous
      chemotherapy did not influence the prevalence or the severity of hot flushes.
      Current antidepressant treatment was, however, significantly associated with a
      higher prevalence and severity of most menopausal symptoms, including hot flushes
      and sweats (p = 0.008). The severity of hot flushes and sweats was significantly
      correlated with self-assessed effects on overall quality of life (r(s) = 0.47);
      56.4% of the respondents believed that menopausal symptoms had affected their
      partner's quality of life, the strongest correlations being with severity of
      sexual symptoms (r(s) = 0.56) and vaginal dryness (r(s) = 0.5). Only 21% of women
      experiencing hot flushes were receiving any treatment for hot flushes, with most
      women describing no knowledge or poor knowledge of treatment options.
      CONCLUSIONS: The majority of women receiving treatment for breast cancer report
      menopausal symptoms, which negatively correlate, not only with their own, but
      also with their partner's quality of life. Most women experiencing hot flushes
      are not receiving treatment due to lack of both awareness and confidence in the
      existing treatment options.

PMID- 16428126
TI  - Effects of tibolone on blood flow resistance and intima-media thickness of the
      carotid arteries: effect of time since menopause.
AB  - OBJECTIVE: The aim of this prospective study was to evaluate the effects of
      tibolone on carotid atherosclerosis in healthy postmenopausal women. METHODS:
      Twenty-five healthy postmenopausal women were included in the study. Patients
      received tibolone 2.5 mg daily for 6 months. Resistance indices of the common
      carotid artery (CCA), internal carotid artery (ICA), external carotid artery
      (ECA) and vertebral arteries, and intima-media thickness of the CCA were measured
      both at baseline and at the end of the study with ultrasonography. RESULTS: No
      significant differences were observed in the resistance indices of the CCA, ICA,
      ECA and vertebral arteries, as well as intima-media thickness of CCA at 6 months
      in comparison with baseline. Tibolone significantly improved the intima-media
      thickness of the CCA of women who were less than 18 months since menopause.
      CONCLUSION: Overall, these results demonstrate no significant effects of tibolone
      on either intima-media thickness or blood flow resistance in the carotid arteries
      in postmenopausal women. However, the results suggest that tibolone may have a
      positive effect on the vascular system if commenced within 18 months since
      menopause; this warrants further investigation.

PMID- 16428127
TI  - Sex hormones and cerebral hemodynamics.

PMID- 16428129
TI  - Classification ensembles for unbalanced class sizes in predictive toxicology.
AB  - This paper investigates the effects of the ratio of positive-to-negative samples
      on the sensitivity, specificity, and concordance. When the class sizes in the
      training samples are not equal, the classification rule derived will favor the
      majority class and result in a low sensitivity on the minority class prediction.
      We propose an ensemble classification approach to adjust for differential class
      sizes in a binary classifier system. An ensemble classifier consists of a set of
      base classifiers; its prediction rule is based on a summary measure of individual
      classifications by the base classifiers. Two re-sampling methods, augmentation
      and abatement, are proposed to generate different bootstrap samples of equal
      class size to build the base classifiers. The augmentation method balances the
      two class sizes by bootstrapping additional samples from the minority class,
      whereas the abatement method balances the two class sizes by sampling only a
      subset of samples from the majority class. The proposed procedure is applied to a
      data set to predict estrogen receptor binding activity and to a data set to
      predict animal liver carcinogenicity using SAR (structure-activity relationship)
      models as base classifiers. The abatement method appears to perform well in
      balancing sensitivity and specificity.

PMID- 16428130
TI  - Base-line model for identifying the bioaccumulation potential of chemicals.
AB  - The base-line modeling concept presented in this work is based on the assumption
      of a maximum bioconcentration factor (BCF) with mitigating factors that reduce
      the BCF. The maximum bioconcentration potential was described by the multi
      compartment partitioning model for passive diffusion. The significance of
      different mitigating factors associated either with interactions with an organism
      or bioavailability were investigated. The most important mitigating factor was
      found to be metabolism. Accordingly, a simulator for fish liver was used in the
      model, which has been trained to reproduce fish metabolism based on related
      mammalian metabolic pathways. Other significant mitigating factors, depending on
      the chemical structure, e.g. molecular size and ionization were also taken into
      account in the model. The results (r(2)=0.84) obtained for a training set of 511
      chemicals demonstrate the usefulness of the BCF base line concept. The
      predictability of the model was evaluated on the basis of 176 chemicals not used
      in the model building. The correctness of predictions (abs(logBSF(Obs)
      logBCF(Calc))=0.75)) for 59 chemicals included within the model applicability
      domain was 80%.

PMID- 16428131
TI  - Alternative QSAR models for selected estradiol and cytochrome P450 ligands:
      comparison between classical, spectroscopic, CoMFA and GRID/GOLPE methods.
AB  - The performance of the spectroscopic EVA (eigenvalue) and EEVA (electronic
      eigenvalue) methods was tested with data sets applying coumarin 7-hydroxylation
      inhibitors (28 compounds) for cytochrome P450 mouse CYP2A5 and human CYP2A6
      enzymes and 11ss-, 16a-, and 17a-substituted estradiol derivatives (30 compounds)
      for the lamb uterine estrogen receptor, and compared with the performance of the
      classical Hansch-type, CoMFA and GRID/GOLPE methods. Besides the internal
      predictability, the external predictability of the models was tested with several
      randomized training and test sets to ensure the validity and reliability of the
      models. Partial least squares (PLS) regression was employed as a general
      statistical tool with the EVA and EEVA methods. Some supplementary models were
      also built using only one PLS component with McGowan's volumes (MgVol and
      MgVol(2)) as additional descriptors and employing multiple linear regression
      (MLR) as the modelling tool. In general, both the internal and external
      performance of the EVA model, and more especially the EEVA model, with one PLS
      component and MgVol parameters was satisfactory, being either as good as or
      clearly better than that of the Hansch-type, CoMFA and GRID/GOLPE models.

PMID- 16428132
TI  - Improving the performance of SOMFA by use of standard multivariate methods.
AB  - Self-Organizing Molecular Field Analysis (SOMFA) comes with a built-in regression
      methodology, the Self-Organizing Regression (SOR), instead of relying on external
      methods such as PLS. In this article we present a proof of the equivalence
      between SOR and SIMPLS with one principal component. Thus, the modest performance
      of SOMFA on complex datasets can be primarily attributed to the low performance
      of the SOMFA regression methodology. A multi-component extension of the original
      SOR methodology (MCSOR) is introduced, and the performances of SOR, MCSOR and
      SIMPLS are compared using several datasets. The results indicate that in general
      the performance of SOMFA models is greatly improved if SOR is replaced with a
      more sophisticated regression method. The results obtained for the Cramer (CBG)
      dataset further underline the fact that it is a very poor benchmark dataset and
      should not be used to evaluate the performance of QSAR techniques.

PMID- 16428133
TI  - Quantitative structure-activity relationship modeling of insect juvenile hormone
      activity of 2,4-dienoates using computed molecular descriptors.
AB  - Juvenile hormone (JH) activity of one hundred and eighty 2,4-dienoates reported
      for the larvae/pupae of six insect species was modeled using 915 atom pairs and
      258 global molecular descriptors (topological and geometrical). Ridge regression,
      principal component regression and partial least square regression methods were
      used to model each of the JH activities. The use of all of the available
      parameters did not yield any good models, and extensive predictor trimming was
      necessary to improve the models. Ridge regression was found to give the best
      results among the three statistical tools used. The top ten molecular descriptors
      selected based on the t-statistic for each of the six models were found to be
      mostly atom pairs containing heteroatoms and topochemical descriptors. This
      suggests the importance of the chemical nature of the ligand rather than mere
      space-filling as the basis of the JH bioactivity. The residual plots indicate the
      existence of some non-linear relations, and recursive partitioning was used to
      capture any nonlinear relation between the bioassays and the molecular
      descriptors.

PMID- 16428136
TI  - Analysis of human plasma proteome by 2DE- and 2D nanoLC-based mass spectrometry.
AB  - We compared the 2DE coupled to MALDI-TOF-MS and ESI-MS/MS analysis (2DE-MS) and
      the on-line 2D nanoLC, followed by nanoESI-MS/MS analysis (2DLC-MS), for the
      separation and identification of proteins in high abundance protein-depleted
      human plasma. Identification of proteins in the plasma by the two methods
      demonstrated that the majority of the identified protein set was unique to each
      method. Therefore, if a comprehensive coverage of the proteome identification is
      desired, it is ideal to apply both methods. The 2DE-MS method is amenable to
      protein spot-based quantitation, whereas the 2DLC-MS method may provide an
      advantage of the high throughput application.

PMID- 16428137
TI  - Effect of ionizing radiation on rat tissue: proteomic and biochemical analysis.
AB  - Reactive oxygen species (ROS), generated by ionizing radiation, has been
      implicated in its effect on living tissues. We confirmed the changes in the
      oxidative stress markers upon irradiation. We characterized the changes in the
      proteome profile in rat liver after administering irradiation, and the affected
      proteins were identified by MALDI-TOF-MS and ESI-MS/MS. The identified proteins
      represent diverse sets of proteins participating in the cellular metabolism. Our
      results demonstrated that proteomics analysis is a useful method for
      characterization of a global proteome change caused by ionizing radiation to
      unravel the molecular mechanisms involved in the cellular responses to ionizing
      radiation.

PMID- 16428138
TI  - Neural network-based analysis of thiol proteomics data in identifying potential
      selenium targets.
AB  - Generation of a monomethylated selenium metabolite is critical for the anticancer
      activity of selenium. Because of its strong nucleophilicity, the metabolite can
      react directly with protein thiols to cause redox modification. Here, we report a
      neural network-based analysis to identify potential selenium targets. A reactive
      thiol specific reagent, BIAM, was used to monitor thiol proteome changes on 2D
      gel. We constructed a dynamic model and evaluated the relative importance of
      proteins mediating the cellular responses to selenium. Information from this
      study will provide new clues to unravel mechanisms of anticancer action of
      selenium. High impact selenium targets could also serve as biomarkers to gauge
      the efficacy of selenium chemoprevention.

PMID- 16428139
TI  - Analysis of protein redox modification by hypoxia.
AB  - We examined hypoxia-induced changes in global thiol proteome profile in human
      prostate cancer cells using a BIAM-based display method. We analyzed the kinetics
      of protein thiol modification by using a pattern recognition algorithm, self
      organizing maps (SOM) clustering, and identified the BIAM-labeled proteins by
      MALDI-TOF and ESI-tandem mass spectrometry. We found 99 out of 215 of total BIAM
      labeled proteins were affected by hypoxia treatment and, yet, with diverse
      patterns and kinetics of redox modification. Our study proved that proteomics
      analysis employing the BIAM-labeling method can provide valuable information
      pertaining to global changes in the redox status of proteins in response to
      hypoxia.

PMID- 16428140
TI  - Some properties of free and immobilized alpha-amylase from Penicillium
      griseofulvum by solid state fermentation.
AB  - Alpha-amylase was produced from Penicillium griseofulvum by an SSF technique.
      Alpha-amylase was immobilized on Celite by an adsorption method. Various
      parameters, such as effect of pH and temperature, substrate concentration,
      operational and storage stability, ability to hydrolyze starch and products of
      hydrolysis were investigated; these findings were compared with the free enzyme.
      The activity yield of immobilization was 87.6%. The optimum pH and temperature
      for both enzymes were 5.5 degrees C and 40 degrees C, respectively. The thermal,
      and the operational and storage stabilities of immobilized enzyme were better
      than that of the free enzyme. Km and Vmax were calculated from Lineweaver-Burk
      plots for both enzymes. Km values were 9.1 mg mL(-1) for free enzyme, and 7.1 mg
      mL(-1) for immobilized enzyme. The Vmax of the immobilized enzyme was
      approximately 40% smaller than that of the free enzyme. The hydrolysis ability of
      the free and immobilized enzyme were determined as 99.3% and 97.9%, respectively.
      Hydrolysis products of the a-amylase from P. griseofulvum were maltose,
      unidentified oligosaccharides, and glucose.

PMID- 16428143
TI  - Perceptions on the treatment of psoriasis.

PMID- 16428141
TI  - Alcalase-catalyzed, kinetically controlled synthesis of a precursor dipeptide of
      RGDS in organic solvents.
AB  - The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide
      of RGDS, Z-Asp-Ser-NH2 in organic solvents was studied. Alcalase, an industrial
      alkaline protease, was used to catalyze the synthesis of the target dipeptide in
      water-organic cosolvents systems with Z-Asp-OMe as the acyl donor and Ser-NH2 as
      the nucleophile. Acetonitrile was selected as the organic solvent from
      acetonitrile, ethanol, methanol, DMF, DMSO, ethyl acetate, 2-methyl-2-propanol,
      and chloroform tested under the experimental conditions. The conditions of the
      synthesis reaction were optimized by examining the effects of several factors,
      including water content, temperature, pH, and reaction time on the Z-Asp-Ser-NH2
      yields. The optimum conditions are pH 10.0, 35 degrees C, in acetonitrile/Na2CO3
      NaHCO3 buffer system (85:15, v/v), 6 h, with a dipeptide yield of 75.5%.

PMID- 16428144
TI  - We need more cross-disciplinary communication.

PMID- 16428145
TI  - The use of ciclosporin in psoriasis.
AB  - Ciclosporin is a cyclic undecapeptide discovered in the 1970s to possess a potent
      inhibitory action on T lymphocytes. The subsequent discovery, in 1979, that it
      was remarkably effective in treatment of psoriasis transformed thinking about the
      nature of the disease, which subsequently became generally recognized as
      autoimmune in nature. Ciclosporin remains one of the most effective and rapidly
      acting treatments currently available for psoriasis. Virtually all the diverse
      manifestations of this disease can respond. The main side effects are
      nephrotoxicity and hypertension. There is considerable variation between
      individuals in susceptibility to these so careful monitoring is required.
      Ciclosporin should be used in single or intermittent short courses for all except
      the most severe cases as this is safer than continuous treatment. The rate of
      improvement depends very much on the dose, which ranges from 2 to 5.0 mg/kg/day.
      Ciclosporin can be combined with any topical treatment and a useful dose-sparing
      effect can be achieved in this way if patients are compliant. In severe cases
      ciclosporin is often used in combination with other systemic antipsoriatic drugs
      in order to spare the dose of each agent and reduce toxicity. Concurrent or
      intercurrent use of ultraviolet therapy is discouraged due to the increased risk
      of non-melanoma skin cancer. This article reviews the mode of action,
      pharmacokinetics, indications, contraindications, side effects, dosage regimens,
      pretreatment screening and monitoring, drug interactions, and use of treatment
      combinations with ciclosporin in the management of psoriasis.

PMID- 16428146
TI  - Toxic epidermal necrolysis (TEN) Lyell's syndrome.
AB  - Toxic epidermal necrolysis, a unique rapidly developing mucocutaneous reaction
      pattern, characterized by sheets of erythema, necrosis and bullous detachment of
      the epidermis, closely resembling that of scalding of the skin and rapidly fatal,
      was described by Lyell, and is now recognized as toxic epidermal necrolysis (TEN)
      Lyell's syndrome. The condition is indistinguishable from staphylococcal scalded
      skin syndrome (SSSS), and generalized fixed drug eruption. Hence, there has
      always been controversy as regards terminology. It is well conceived that TEN is
      equivalent to Stevens-Johnson syndrome (SJS), at its greatest severity. TEN,
      therefore, is a great challenge and warrants instant attention based on a
      thorough knowledgeable background covering several related facets including the
      recent advances in pathogenesis and management strategies. The details contained
      in the following text should prove very useful in the comprehension of a largely
      intractable entity.

PMID- 16428147
TI  - A randomized double-blind study to assess the effects of silicic acid compared to
      placebo in patients with mild to moderate acne.
AB  - OBJECTIVE: To establish the efficacy and safety of silicic acid in comparison to
      placebo in patients with mild to moderate acne vulgaris. PATIENTS AND METHODS:
      Forty adult patients with facial acne vulgaris were randomized to silicic acid or
      placebo applied twice daily for 8 weeks. Efficacy was assessed by number of acne
      lesions, acne grade and sebum excretion rate (SER). Clinical safety and tolerance
      were also assessed and global assessments and psychological profile
      questionnaires were completed. RESULTS: There were no significant differences
      between silicic acid and placebo in the number of inflamed lesions (the primary
      efficacy variable). In contrast, silicic acid significantly reduced the number of
      non-inflamed lesions, total acne lesions and the acne grade after 8 weeks and SER
      over 4 weeks when compared with placebo. There were no significant differences
      between silicic acid and placebo in the responses to the questionnaires or the
      global assessments after 8 weeks. Silicic acid was well tolerated with few
      adverse events. CONCLUSIONS: Silicic acid may have a positive treatment effect on
      the non-inflammatory component of mild to moderate facial acne. These preliminary
      findings now need to be confirmed by similar studies.

PMID- 16428148
TI  - The rise of the generic drug market and its implications for dermatology.
AB  - BACKGROUND: Recent data from the pharmaceutical industry suggest that generic
      medications are occupying an increasing percentage of the prescription drug
      market. OBJECTIVE: The objective of this paper was to review the trends in
      branded and generic dermatological and overall medications in the United States.
      METHODS: A thorough literature search of research papers for the period 1990-2003
      was performed. In addition, we utilized data from a number of medical databases
      to obtain and compare information on the manufacturing, production, patents and
      prescription of branded and generic drugs. RESULTS: Two of the top 10 drugs used
      exclusively for dermatological conditions prescribed in 2003 were generics. For
      all drugs, the number of generic equivalents increased from 2 (in 1990) to 6 (in
      2003) of the top 10 prescription drugs. CONCLUSIONS: The economic, social and
      scientific implications of the rising prominence of generic drugs are incredibly
      complex. Dermatologists, pharmacists, pharmacy benefit managers, and health
      policy makers should consider medication decisions carefully.

PMID- 16428149
TI  - Treatment costs of three nail lacquers used in onychomycosis.
AB  - OBJECTIVE: To assess the daily treatment costs and the average cost-effectiveness
      of three topical onychomycosis therapies - amorolfine 5% and ciclopirox 8% nail
      lacquers and tioconazole 28% nail solution - when used as indicated in France,
      the UK, Germany and Italy. METHODS: The quantity of drug required and nail size
      measurements were investigated and, knowing the cost per bottle of each study
      drug, used to calculate the average treatment cost per patient. Using the
      prevalence of infection data, the weighted average total treatment cost per
      patient and hence the weighted average daily treatment cost and cost per patient
      cured, were calculated. RESULTS: Amorolfine was consistently more cost-effective
      in terms of weighted average daily treatment cost and cost per patient cured than
      ciclopirox and tioconazole, when all therapies were used as indicated to treat
      onychomycosis. In France, for example, the weighted average daily treatment cost
      of amorolfine was found to be euro 0.23 and euro 0.40 when used once and twice a
      week, respectively; the cost per patient cured for amorolfine was euro 84. By
      comparison, the weighted average daily treatment cost of ciclopirox was found to
      be euro 0.81; the cost per patient cured was euro 252. CONCLUSIONS: When used as
      indicated, amorolfine 5% nail lacquer is more cost-effective than ciclopirox 8%
      and tioconazole 28% for onychomycosis of toenail, fingernail or both in males and
      females in France, UK, Germany and Italy.

PMID- 16428150
TI  - Effectiveness of climatotherapy at the Dead Sea for psoriasis vulgaris: A
      community-oriented study introducing the 'Beer Sheva Psoriasis Severity Score'.
AB  - BACKGROUND: Climatotherapy at the Dead Sea (CDS) is a therapeutic modality for
      moderate to severe psoriasis vulgaris. OBJECTIVE: To evaluate the effectiveness
      of CDS in patients with psoriasis, using the PASI score and a novel simplified
      tool for the assessment of psoriasis - the Beer Sheva Psoriasis Severity Score
      (BPSS). METHODS: A total of 70 patients with psoriasis vulgaris were treated by
      CDS. In all patients, the severity of psoriasis was assessed before and after CDS
      using PASI score and BPSS. BPSS includes eight items that are recorded by the
      physician (total severity of the disease, and seven items relating to the
      physical distribution of the disease) and eight items that are recorded by the
      patient (total severity, physical and psychological severity, pruritus and
      assessment of involvement in the face, nails, palms and soles and genital
      regions). RESULTS: The study included 70 patients (40 men, 30 women; age 19-78
      years). There was a 75.9% reduction in PASI score, from a mean of 16.6+/-11.0
      before treatment to 4.0+/-4.2 after treatment (p<0.001). There was a 57.5%
      reduction in BPSS, from a mean of 72.8+/-19.6 before treatment to 31.0+/-21.2
      after treatment (p<0.001). PASI score significantly correlated with BPSS before
      CDS treatment (r = 0.59, p<0.001) and after CDS treatment (r = 0.53, p<0.001).
      CONCLUSION: CDS is an effective therapy for patients with psoriasis, as evaluated
      by either PASI score or BPSS. BPSS was considered shorter and more user-friendly
      by the participating physicians.

PMID- 16428151
TI  - Infliximab for inpatient psoriasis management--is there a role?
AB  - BACKGROUND: While outpatient management is a realistic goal for most psoriasis
      patients, inpatient hospitalization may be required for severe acute
      exacerbations. The paradigm of inpatient psoriasis treatment has changed as
      reflected in an overall decline in admissions as well as the introduction of
      several new agents for patients with moderate to severe disease. With these
      changes as well as the changes in inpatient health care delivery, the costs of
      inpatient psoriasis therapy need to be re-examined. PURPOSE: To determine the
      mean charges and length of stay associated with inpatient admissions for
      psoriasis and compare these with the potential charges for infliximab
      administration in the inpatient setting. METHODS: Inpatient psoriasis admissions
      were identified from the State of Maryland Health Services Cost Review Commission
      (HSCRC) non-confidential database from 1994 to 2003. The mean length of stay and
      total charges associated with psoriasis admissions were determined and adjusted
      to current values based upon the hospital costs component of the Consumer Price
      Index (CPI). The potential charges for infliximab administration were then
      estimated according to a presumed treatment paradigm and based on median Medicare
      reimbursement rates. RESULTS: The mean length of stay for an inpatient psoriasis
      patient was 4.9 days, and the mean CPI adjusted total charges from 1994 to 2003
      were $6736. In 2003, the mean total charges for a psoriasis admission were $7578.
      The total estimated charges for a 2-day inpatient hospitalization with infliximab
      administration were $6256. CONCLUSIONS: Although infliximab therapy is not
      currently approved for psoriasis therapy it does have efficacy and may be a first
      line therapy for inpatient treatment. Additionally, the high cost of infliximab
      may be offset by a decreased overall length of stay and its use is therefore
      potentially justified.

PMID- 16428152
TI  - The comorbid state of psoriasis patients in a university dermatology practice.
AB  - BACKGROUND: Psoriasis treatment is frequently complicated by the various types
      and severities of disease as well as the large number of therapies available.
      Another critical consideration in treatment planning is the presence of comorbid
      diseases. PURPOSE: The purpose of this study was to evaluate the relative
      prevalence of major comorbid disease states in patients with psoriasis and to
      identify significant predictors of these concurrent diseases in such patients.
      METHODS: A retrospective chart review of 753 patients from an academic
      dermatology practice was performed. The patients were identified by ICD-9 code
      for psoriasis in billing records of patients seen between 1997 and 2000. Data on
      comorbidities were compiled from review of electronic chart notes from all
      physician visits in the university practice. RESULTS: Comorbid diagnoses were
      listed in 551 out of 753 (73%) charts. As would be expected, hypertension,
      dyslipidaemia, diabetes and heart disease were the most common comorbidities;
      renal failure and hepatitis were least likely. Hepatitis was associated with use
      of systemic therapies (odds ratio = 2.19) and non-white race. When compared with
      national prevalence estimates, psoriasis patients had increased heart disease,
      hypertension, diabetes and emphysema; however, these findings must be interpreted
      with some caution. CONCLUSIONS: Comorbid diseases are common in psoriasis
      patients and should be taken into account during treatment planning and
      surveillance; they may pose unique challenges in caring for patients with
      psoriasis, particularly those requiring systemic therapy.

PMID- 16428153
TI  - The role of commercial tanning beds and ultraviolet A light in the treatment of
      psoriasis.
AB  - BACKGROUND: Phototherapy is an effective, safe psoriasis treatment administered
      via office-based units or home devices. There is controversy over the use of
      commercial tanning beds; ultraviolet B (UVB) has documented efficacy although
      commercial beds emit largely UVA. OBJECTIVE: To determine the efficacy of UVA and
      the role of commercial tanning beds in treating psoriasis. METHODS: A literature
      search of UVA and commercial tanning was performed. RESULTS: UVA can be effective
      for psoriasis, but achieving the high doses required may not be practical.
      Tanning beds do emit UVB although amounts are variable. Because of variability in
      UVA and UVB output in different tanning bulbs, it is difficult to predict
      response rates using commercial tanning beds. CONCLUSIONS: UVA can be used to
      treat psoriasis but may not be practical. Commercial tanning beds, emitting both
      UVA and UVB, have a role in treating psoriasis as an alternative to office-based
      therapy.

PMID- 16428154
TI  - Combination of oral terbinafine and topical ciclopirox compared to oral
      terbinafine for the treatment of onychomycosis.
AB  - BACKGROUND: Treatment of onychomycosis has recently been enhanced by the
      introduction of combination therapies. OBJECTIVE: To evaluate the efficacy of a
      combination therapy of ciclopirox nail lacquer and oral terbinafine compared to
      oral terbinafine monotherapy for the treatment of onychomycosis caused by
      dermatophytes. PATIENTS AND METHODS: Eighty patients with onychomycosis were
      randomly assigned to receive either oral terbinafine 250 mg/day for 16 weeks or a
      combination of oral terbinafine 250 mg/day for 16 weeks and topical ciclopirox
      nail lacquer once daily for 9 months. Both groups were followed up for 9 months
      from start of treatment. RESULTS: After 9 months of treatment, the mycological
      cure rates were 22/34 (64.7%) for the terbinafine-only group and 30/34 (88.2%)
      for the combination therapy group (p<0.05). No significant difference was noted
      in the complete cure rate. CONCLUSION: Combination therapy of oral terbinafine
      and ciclopirox nail lacquer is a safe and more effective treatment for
      onychomycosis than terbinafine alone, especially in younger patients and in
      shorter-duration onychomycosis.

PMID- 16428155
TI  - Comparative efficacy of topical 1% butenafine and 1% clotrimazole in tinea cruris
      and tinea corporis: a randomized, double-blind trial.
AB  - Localized tinea cruris and tinea corporis can be treated by topical imidazoles
      (clotrimazole) or newer topical agents like butenafine, a benzylamine derivative
      with fungicidal activity. The therapeutic efficacy of these two agents was
      compared in this study. Eighty patients, diagnosed clinically to have tinea
      cruris or localized tinea corporis and confirmed on KOH examination, were
      randomly assigned to one of the two treatment groups in a double-blind manner;
      butenafine once daily for 2 weeks or clotrimazole twice daily for 4 weeks. Follow
      up was done at 1, 2, 4 and 8 weeks. Clinical assessment score and KOH examination
      were performed at each visit. Butenafine recipients exhibited higher clinical
      cure as compared with clotrimazole recipients at the end of 1 week (26.5% vs
      2.9%) as well as higher mycological cure (61.7% vs 17.6%). However, this
      difference was not statistically significant at 4 and 8 weeks of treatment.

PMID- 16428156
TI  - Topical salicylic acid gel as a treatment for molluscum contagiosum in children.
AB  - OBJECTIVE: To determine if the application of salicylic acid gel or phenol
      solution affected resolution of molluscum contagiosum (MC) lesions in children.
      PATIENTS AND METHODS: This was a randomized, prospective controlled trial with
      two treatment arms and one vehicle arm for treatment of MC in children. The trial
      was set in the dermatology outpatient clinics of a teaching hospital and a
      district general hospital. A total of 114 children were enrolled in the study
      (age range 1-15 years) over a 4-year period; 83 of the children completed the
      study. Patients were randomized to receive one of three possible treatments:
      monthly vehicle application of 70% alcohol, monthly application of 10% phenol in
      70% alcohol once or twice weekly 12% salicylic acid gel. All patients also
      received treatment with daily aqueous cream to reduce eczema. They returned
      monthly to the clinic for treatment and counting of MC lesions. They were
      reviewed either until complete resolution or up to 6 months, whichever occurred
      sooner. The main outcome measure was the time taken for complete resolution of MC
      lesions. RESULTS: In the intention-to-treat analysis there was no difference
      between treatment arms when the 31 non-completers were analysed as failures (log
      rank test: p = 0.38). In an 'as treated' analysis, 16 of 27 children (59.2%: 95%
      confidence interval 30.2-88.3) had cleared with vehicle, 18 of 32 (56.3%, 30.3
      82.2) with phenol solution and 21 of 24 (87.5%, 50.1-124.9) with salicylic acid
      gel (log-rank test: p = 0.03). On an as treated basis, salicylic acid was
      significantly better at clearing MC than dilute phenol (p = 0.006). The treatment
      in all groups was very well tolerated or acceptable in 93% of children.
      CONCLUSION: Our results suggest that topical salicylic acid may be beneficial in
      speeding resolution of MC in children. Dilute phenol application does not appear
      to affect the disease course.

PMID- 16428157
TI  - Risk factors for incomplete excision of squamous cell carcinomas.
AB  - OBJECTIVE: The aim of this study was to identify risk factors for incomplete
      excision of squamous cell carcinomas (SCCs). PATIENTS AND METHODS: A cross
      sectional study of 369 patients who underwent a primary excision of SCCs was
      performed within an outpatient and a hospital plastic surgery department setting.
      RESULTS: Incomplete excision occurred in 25 of 369 primary excisions of SCC
      (6.8%). Location of the tumors on the forehead, temples, peri-auricular region,
      ears, cheeks, nose, lips or neck was significantly associated with incomplete
      excision of the tumors. In particular, high incomplete excision proportions were
      observed for tumors located on the ears (16.7%), neck (16.7%), temples (11.1%),
      nose (10.8%) or lips (7.1%). Incomplete excision of SCC was associated with the
      setting of the operation in the hospital as compared to ambulatory settings (p =
      0.046) and was inversely associated with the specimen thickness (p = 0.002).
      There was no statistically significant association between incomplete excision of
      SCC and gender, age, clinical appearance of the lesion (suspected SCC vs other
      diagnoses), differentiation pattern, diameter of the tumor, length or width of
      the excised specimen, solar changes or ulceration. CONCLUSION: We recommend that
      in patients with SCCs located in the forehead, temples, periauricular region,
      ears, cheeks, nose, lips or neck surgeons should commence particular surgical
      measures to avoid inadequate excisions of the tumors. In particular, surgeons
      should use wider excisional margins in tumors located in the embryonic fusion
      planes (e.g. eyelids and naso-labial folds).

PMID- 16428158
TI  - Use of trafermin to treat a skin ulcer after repair of a deep auricular
      laceration: a case report.
AB  - We used trafermin (recombinant human basic fibroblast growth factor) to treat a
      skin ulcer (diameter, 1 cm; depth, 2 mm) that developed after an extremely deep
      auricular laceration was sutured. Excellent results were obtained after use of
      trafermin for 2 weeks. To our knowledge, we report the first clinical use of
      trafermin in a patient with a skin ulcer resulting from auricular trauma.
      Trafermin may promise to be an effective treatment for skin ulcers.

PMID- 16428159
TI  - Use of etanercept in treatment of pyoderma gangrenosum in a patient with
      autoimmune hepatitis.
AB  - A 30-year-old female with past medical history of autoimmune hepatitis was sent
      to our clinic for consultation and treatment of refractory pyoderma gangrenosum
      (PG) of bilateral lower extremities. At the time of presentation, she had failed
      treatment with prednisone, azathioprine and local wound care. Treatment options
      were limited by the patient's autoimmune hepatitis. This patient was treated with
      etanercept and a taper of oral prednisone, which resulted in a complete clinical
      cure of her PG. More studies are needed to evaluate the safety and efficacy of
      etanercept for PG in patients with liver disease.

PMID- 16428160
TI  - Adalimumab effectively controlled recalcitrant generalized pustular psoriasis in
      an adolescent.
AB  - Generalized pustular psoriasis is a rare form of psoriasis which may be serious
      and can be fatal. We report here the treatment of an adolescent girl who
      responded to adalimumab after failing to respond to a combination of
      methotrexate, cyclosporin and isotretinoin, and having had a pustular reaction
      that followed the use of etanercept, but might have been triggered by an
      infection.

PMID- 16428161
TI  - Rapid improvement of human orf (ecthyma contagiosum) with topical imiquimod
      cream: report of four complicated cases.
AB  - Orf is a zoonosis caused by an epitheliotropic DNA parapox virus. Human orf is a
      generally benign, self-limiting condition that usually regresses in 6-8 weeks
      without specific treatment. However, it may be accompanied by local symptoms
      including pain, pruritus, lymphangitis and axillary adenitis, or less frequently
      by systemic symptoms such as fever or malaise. Furthermore, it may be complicated
      by erythema multiforme, Stevens-Johnson syndrome, erysipelas, generalized
      mucocutaneous eruption, toxic erythema, eyelid oedema and giant, persistent or
      recurrent lesions in immunocompromised patients. Imiquimod, a potent topical
      immune response modifier, enhances both the innate and acquired immunity by
      stimulation of immune system cells resulting in local antiviral, antitumour and
      immunoregulatory activity. We present, for the first time, four complicated cases
      of orf successfully treated by topical imiquimod resulting in rapid regression of
      both orf and associated lesions. Two of the cases were complicated with erythema
      multiforme, one with recurrent eyelid oedema, and another had giant orf
      associated with axillary lymphadenitis. We suggest that topical imiquimod may be
      an effective and safe therapy for complicated orf cases.

PMID- 16428163
TI  - Prevention of arterial hypertension. Introduction.

PMID- 16428175
TI  - Cytotoxicity of a calcium aluminate cement in comparison with other dental
      cements and resin-based materials.
AB  - The objective of this study was to compare the cytotoxic effects of a calcium
      aluminate cement with several currently used direct restorative materials.
      Specimens of three composites (QuiXfil, Tetric Ceram, Filtek Supreme), one zinc
      phosphate cement (Harvard Cement), one glass ionomer cement (Ketac Molar), and
      one calcium aluminate cement (DoxaDent), were used fresh or after 7-days'
      preincubation in cell culture medium at 37 degrees C, pH 7.2. PVC strips for ISO
      10993-5 cytotoxicity test were used as positive control and glass specimens as
      negative control. L-929 fibroblasts (5-ml aliquots, containing 3 x 10(4)
      cells/ml), cultivated in DMEM with 10% FCS, 1% glutamine, and 1%
      penicillin/streptomycin at 37 degrees C/5% CO2 and trypsinized, were exposed to
      the specimens for 72 h. The cells were harvested, centrifuged, and resuspended in
      500 microl DMEM and then counted in 500 microl DMEM for 30 s with a flow
      cytometer at 488 nm. The analysis of variance comparing the six materials showed
      different influences on L-929 fibroblast cytotoxicity (p <0.0001). The
      cytotoxicity of all specimens diminished with increasing preincubation time (p
      <0.0001). Fresh DoxaDent exhibited the lowest cytotoxicity, followed by QuiXfil.
      Ketac Molar showed the highest cytotoxicity. After 7 days of preincubation,
      Harvard Cement and Filtek Supreme demonstrated more cytotoxicity than the other
      materials (p <0.005).

PMID- 16428176
TI  - Factors associated with oral health-related quality of life in institutionalized
      elderly.
AB  - OBJECTIVE: The aim of this study was to investigate factors associated with the
      oral health-related quality of life (OHRQoL) of institutionalized elderly in
      Germany. MATERIAL AND METHODS: One-hundred-and-fifty-eight subjects from old
      people's homes were selected (mean 82.8 years). OHRQoL was measured using the
      Oral Health Impact Profile (OHIP). Denture characteristics (kind and age of
      denture, retention of removable denture, number of teeth in static occlusion) and
      general issues (age, gender, education level, and general pain status) were
      assessed. All factors were subjected to bivariate testing for their effects on
      the OHIP summary score (OHIP-SC) and to multivariate testing in subjects with
      removable dentures (n = 128); a linear regression model with backward elimination
      was used, with OHIP-SC as the dependent variable. RESULTS: In the context of
      other studies, a median OHIP-SC of 29 indicated highly impaired OHRQoL. According
      to the bivariate analysis, retention, age of denture, number of teeth in static
      occlusion, general pain status, and education all exhibited significant influence
      on OHIP-SC. In the final linear regression model, general pain status, education
      level, and retention of denture remained at a statistically significant level.
      The model explained 34% (R2 = 0.34) of the variance of the OHIP-SC. The kind of
      denture had no significant impact on OHIP-SC. CONCLUSIONS: In contrast to other
      groups, the kind of denture exhibited little impact on OHIP-SC for this highly
      specific collective. However, there were functional aspects of dentures which
      seemed to be important. Non-dental factors had a striking effect on OHRQoL.

PMID- 16428177
TI  - Effects of an intravenous infusion of Ringer's solution on eruption rates of
      incisor teeth in anesthetized rats.
AB  - OBJECTIVE: The vasculature within the socket is reportedly involved in
      determining the position of continuously erupting teeth. Thus, loss of body fluid
      in anesthetized rats, which would affect the vascular physiology, should
      influence tooth movement. We investigated the effects of an infusion of Ringer's
      solution on the systemic arterial blood pressure, regional blood flow at the base
      of the incisor, and axial tooth movement in anesthetized rats to determine the
      cause of tooth displacement. MATERIAL AND METHODS: In the experimental group, the
      animals received intravenous infusions of Ringer's solution at 27 microl/min for
      13 h. In the control group, the animals did not receive the infusion. RESULTS:
      The infusion of Ringer's solution suppressed an increase of the mean arterial
      blood pressure from 86 to 80 mmHg and a decrease of the regional blood flow from
      170 to 217 mV, and increased the eruption rate from 267 to 361 microm/13 h during
      the experimental period. There was a positive correlation between the eruption
      rate and regional blood flow, and a negative correlation between the blood
      pressure and regional blood flow. CONCLUSIONS: These results suggest that an
      infusion of Ringer's solution can cause an increase in the regional blood flow,
      resulting in increased fluid volume, elevated intra-socket pressure, and
      increased eruptive movement. It is possible that the regional vascular volume
      and/or pressure within the socket play an important role in determining the
      position of the incisor.

PMID- 16428178
TI  - Antimicrobial activity of monocaprin: a monoglyceride with potential use as a
      denture disinfectant.
AB  - Monocaprin is a 1-monoglyceride of capric acid that has antimicrobial activity
      against enveloped viruses, certain bacteria, and the yeast Candida albicans.
      Solutions containing monocaprin were formulated and tested in vitro against a
      number of micro-organisms, including species found in the oral cavity and common
      pathogenic species. The antimicrobial activity of monocaprin was tested with
      strains growing on a surface as well as in the planktonic phase. Micro-organisms
      tested were: Streptococcus mutans, Candida albicans, Lactobacillus sp.,
      Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Two sets of
      dilutions were prepared for each test strain; one to be inoculated with the micro
      organism growing in the planktonic phase and the other with the same strain
      growing on a filter paper disk. Control solutions were also prepared to find out
      if any of the excipients were affecting the microbicidal effect of monocaprin.
      Test strains growing on the filter paper surface were less sensitive to
      monocaprin than the same strain growing in its planktonic phase. C. albicans was
      the micro-organism that was most sensitive to monocaprin, but S. mutans also
      showed appreciable sensitivity. The indication that monocaprin may have potential
      as a topical agent against Candida was tested in an open study of denture
      disinfection in 32 patients attending a geriatric daycare centre. A significant,
      but short-term, reduction in counts of Candida on the fitting surface of full
      dentures was observed.

PMID- 16428179
TI  - An in vitro microbial-based model for studying caries-preventive agents.
AB  - OBJECTIVE: The aim of the study was to develop an in vitro microbial-based caries
      model to test potentially caries-preventive agents. MATERIAL AND METHODS: In this
      model, cariogenic Streptococcus mutans biofilms are grown on tooth samples within
      a reaction chamber hermetically surrounded by a bacteria-tight glove box allowing
      the manipulation of specimens during operation. The specimens were mounted in two
      rows on the inner and outer rims of a specimen turntable passing several inlet
      pipes transporting all necessary media. Using 64 lower incisors in 4 experiments,
      a 10 ppm NaF solution and an experimental potentially caries-preventive glycan
      solution were tested compared to a water control. The mean lesion depth was
      determined by confocal laser scanning microscopy. RESULTS: The depths of the
      caries-like lesions showed no statistically significant difference irrespective
      of whether the specimens were mounted on the inner or outer rim of the specimen
      turntable. As expected, the NaF solution inhibited the development of caries-like
      lesions almost completely. The experimental glycan solution revealed a
      statistically significantly lower demineralization depth compared to the control
      and a significantly higher depth compared to the NaF group. The system could be
      operated over a period of more than 9 weeks without unintentional contamination
      and the manipulation of the tooth specimens could be accomplished. CONCLUSIONS:
      In conclusion, our in vitro system is suitable for testing potential caries
      preventive agents in a reproducible way by using whole tooth samples and offers
      full access together with the possibility of manipulating the specimens during
      operation.

PMID- 16428180
TI  - Effect of incomplete crown ferrules on load capacity of endodontically treated
      maxillary incisors restored with fiber posts, composite build-ups, and all
      ceramic crowns: an in vitro evaluation after chewing simulation.
AB  - OBJECTIVE: The aim of this study was to compare the fracture resistance of
      endodontically treated maxillary central incisors with incomplete crown ferrules
      after chewing simulation. MATERIAL AND METHODS: Forty caries-free maxillary
      central incisors were divided into 4 groups (n = 10). Endodontic treatment was
      performed. Teeth were decoronated 2 mm above the cemento-enamel junction (CEJ).
      Group I (control) provided a 360 degrees circumferential 2-mm ferrule. In group
      II, a 2-mm ferrule was present on the palatal aspect (status after occlusal
      overload), and in group III on the facial aspect (status after traumatic injury).
      In group IV, the ferrule was interrupted by bi-proximal cavitations (simulating
      caries treatment). The teeth received glass fiber reinforced posts and composite
      core restorations. All-ceramic crowns were adhesively cemented. Specimens were
      simultaneously exposed to thermal cycling and mechanical loading (1.2 million
      cycles; 6,000 cycles 5 degrees/55 degrees C) and finally statically loaded until
      failure in a universal testing machine (crosshead speed = 1 mm/min). For
      statistical analysis, the Kruskal-Wallis test was applied followed by the Mann
      Whitney U-test as post hoc testing. RESULTS: The median fracture load values
      (min./max.) were: group I = 502 (326/561), group II = 658 (280/827), group III =
      899 (396/1176), and group IV = 360 (279/646). Analysis revealed statistically
      significant differences between test groups, except between groups I and IV and
      groups II and IV. CONCLUSIONS: The fracture resistance of endodontically and
      post/core restored teeth is dependent on the degree of tooth conservation. An
      incomplete crown ferrule is associated with greater variation in load capacity
      and, despite high fracture values, inclines to fracture.

PMID- 16428181
TI  - A resin-modified glass ionomer cement barrier for treating degree II furcation
      defects: a pilot study in dogs.
AB  - OBJECTIVE: The aim of this study was to evaluate in an animal model the healing
      of degree II furcation defects treated with: an experimental barrier of resin
      modified glass-ionomer cement (GIC), a polylactic acid barrier (GUI), and flap
      surgery (CTR). MATERIAL AND METHODS: In 3 beagles, 18 class II furcation defects
      were surgically produced in mandibular and maxillary premolars and exposed to
      plaque accumulation for 21 days. Following a full flap, notches were made at the
      base to the bone defect. GIC barriers were prepared immediately before use from a
      commercial product and fit to place with the same product. The GIC barriers were
      removed after 30 days and the dogs euthanized after 120 days. Histologic sections
      were analyzed in a computer-assisted microscope. Epithelium, new cementum with
      inserting fibers, and connective tissue lining the root surface in-between
      notches were measured and medians of percentage values calculated. RESULTS: In
      the GIC, epithelium constituted 3.5% (median values) of the notch-to-notch root
      area; new cementum was 83.6% and connective tissue 12.9%. These values were 0%,
      73.6%, and 26.4% for the GUI group and 35.6%, 43.2%, and 0% for the CTR group.
      Bone fill median values were 54.3% for GIC, 20.6% for GUI, and 24.6% for CTR.
      CONCLUSION: GIC and GUI prevented epithelial migration and promoted the formation
      of new periodontal tissues in experimentally induced class II furcation defects
      in dogs.

PMID- 16428182
TI  - Dental and oral radiographic findings in first-year university students in 1982
      and 2002 in Helsinki, Finland.
AB  - OBJECTIVE: This study is part of a larger research program, at the Finnish
      Student Health Service in Helsinki, in which changes in the dental and oral
      health of first-year university students (born in Helsinki) in the years 1982 and
      2002 were compared. MATERIAL AND METHODS: Panoramic radiographs were taken of 176
      students in 1982, mean age 19.8 years (SD+/-0.7), and of 231 in 2002, mean age
      20.2 (SD+/-0.7). DMFT index, caries and periapical changes, alveolar bone
      resorption, wisdom teeth, supernumerary, missing, and persisting deciduous teeth
      were evaluated from the radiographs. The chi-squared test and non-parametric
      tests were used to analyze the statistical significance of differences between
      the study groups and between genders. RESULTS: The DMFT index diminished from
      11.0 (SD +/- 4.2) to 2.9 (SD +/- 3.3) (p < 0.0001). In 2002, 27.9% of the
      students had a DMFT index of zero (in 1982, 0%, p < 0.000). The mean number of
      endodontically treated teeth diminished from 0.1 to 0.03 (p < 0.05). The number
      of impacted wisdom teeth increased in males from mean 0.41 to 0.69 (p < 0.05).
      CONCLUSIONS: An improvement in dental health was obvious in the year 2002. The
      favorable change in DMFT index is a trend that has been going on for several
      decades in Finland, probably as a result of the use of fluorides and better
      education in dental hygiene. The change might also be connected with improved
      general health.

PMID- 16428183
TI  - Influence of the ice-hockey environment on taking up snuff: an interview study
      among young males.
AB  - In Sweden, snuff-use is an established and accepted phenomenon in society,
      especially in connection with certain sports. The aim of this qualitative study
      was to analyze and describe the psychosocial environment influencing young male
      ice-hockey players into starting to use snuff. The study sample comprised 16 male
      participants between 15 and 32 years of age strategically selected for being
      active or having been active as ice-hockey players--snuff-users and non-users
      alike. A grounded theory design, including in-depth interviews, was used to
      generate a theory from data and thereby create theoretical concepts explaining
      social phenomena, human behavior, and process. An interview guide containing
      different themes was used to cover the study area. Five higher-order categories
      were developed and labeled: having a role model, residing in a consenting
      environment, experiencing performance demands, experiencing a sense of community
      and creating an image. Socialization in and through psychosocial norms of the ice
      hockey environment was identified as a core category describing the central
      meaning of the informants' experiences of snuff in the ice-hockey environment. In
      the present study, the identified categories that integrate within the
      environment in which the young people reside and pursue their sports activities
      have been interpreted as factors enhancing the commencement of snuff-use. We
      suggest health promotion activities within the ice-hockey environment based on a
      health psychology model of planned behavior.

PMID- 16428184
TI  - Tooth wear in maxillary anterior teeth from 14 to 23 years of age.
AB  - Using a planimetric method, the size of horizontal wear facets on maxillary
      anterior teeth was studied longitudinally in the permanent dentition of 35
      subjects at ages 14, 18, and 23?years. The study subjects had not previously
      undergone any orthodontic treatment and had Class I occlusion. We studied the
      association between the amount of wear and reported parafunctions and maximal
      bite force. Total wear areas in age groups 14, 18, and 23 years were 29.5 mm2 (SD
      11.4), 39.1 mm2 (SD 12.7), and 45.0 mm2 (SD 13.0), respectively. The total wear
      area increased significantly both from 14 to 18 years of age and from 18 to 23
      years of age (p <0.0001). Between 18 and 23?years of age, the maxillary canines
      showed strongest wear, although the central incisors had largest wear facets. It
      can be concluded that wear of permanent anterior teeth is a continuous phenomenon
      in adolescence and young adulthood.

PMID- 16428185
TI  - Subjective reactions to intervention with artificial interferences in subjects
      with and without a history of temporomandibular disorders.
AB  - In a previous double-blind randomized controlled study, subjects with a history
      of temporomandibular disorder (TMD) reacted to artificial interference with more
      signs of TMD than did subjects with no TMD history. In the present study, we
      analysed the subjective reactions of these individuals on several symptom scales.
      Every day during the 2-week follow-up period, the subjects rated the intensity of
      their symptoms on 9 VAS scales (occlusal discomfort, chewing difficulties, tender
      teeth, fatigue in the jaws, headache, facial pain, opening difficulty, bruxism,
      ear symptoms). Subjects with a history of TMD and true interferences reported
      stronger symptoms than subjects with no TMD history and placebo interferences.
      The most prominent symptoms were occlusal discomfort and chewing difficulties.
      The difference in outcome between the groups with and without a TMD history
      suggests that there are individual differences in vulnerability to occlusal
      interferences. It is likely that the etiological role of occlusal interferences
      in TMD has not been correctly addressed in previous studies on artificial
      interferences.

PMID- 16428186
TI  - Autoantibodies against inner ear proteins in patients with delayed endolymphatic
      hydrops and unilateral juvenile deafness.
AB  - CONCLUSIONS: Patients with the contralateral type of delayed endolymphatic
      hydrops (DEH) may undergo an autoimmune attack against the other inner ear. As
      patients with unilateral juvenile deafness show no progression, despite lengthy
      observation, the autoantibody against the 68-kDa protein may be unrelated to the
      pathogenesis of DEH. OBJECTIVE: The contralateral type of DEH is believed to have
      an autoimmune etiology, and sometimes develops from unilateral juvenile deafness.
      The purpose of this study was to determine whether autoantibodies are
      pathogenetically important in DEH. MATERIAL AND METHODS: Sera from 9 patients
      with DEH, 18 patients with profound unilateral juvenile hearing loss and 15
      control volunteer without inner ear diseases were investigated by means of
      Western blot assay against rat inner ear proteins. RESULTS: Among 8 patients with
      the contralateral type of DEH, 6 (75%) showed at least 1 reactive band on Western
      blotting. The protein that reacted most frequently had a molecular weight of 28
      kDa, which was consistent with our previous results. Among 18 patients with
      unilateral juvenile deafness, 5 (28%) showed reactive bands, exclusively at 68
      kDa.

PMID- 16428187
TI  - Therapeutic efficacy of magnesium after acoustic trauma caused by gunshot noise
      in guinea pigs.
AB  - CONCLUSIONS: The present findings show that magnesium administration can
      significantly reduce threshold shift 7 days after gunshot noise exposure.
      However, this improvement seems to be temporary, suggesting a probable advantage
      in prolonging the treatment. OBJECTIVE: To evaluate the therapeutic efficacy of
      magnesium administration after hearing loss induced by gunshot noise. MATERIAL
      AND METHODS: Forty-eight guinea pigs were exposed to an impulse noise (blank shot
      from a rifle; 170 or 176 dB SPL peak). The therapeutic efficacy of magnesium was
      evaluated by administering either the treatment or a placebo to the traumatized
      animals for 7 days, beginning 1 h after the trauma. Auditory function was
      explored for up to 14 days of recovery by recording the compound action potential
      in the round window. The functional study of hearing was supplemented by
      histological analysis. RESULTS: The threshold shifts of the 170-dB SPL group that
      received magnesium were significantly lower than those of controls after 2 and 7
      days of recovery, but no significant difference was evidenced at 14 days in this
      group, nor at any time in the 176-dB SPL group. Animals treated with magnesium
      after the 176-dB SPL exposure had a significant reduction in hair cell loss in
      the basal region.

PMID- 16428188
TI  - Antimicrobial resistance in Haemophilus influenzae isolated from the nasopharynx
      among Japanese children with acute otitis media.
AB  - CONCLUSION: High prevalence of penicillin-binding protein (PBP) gene mutated
      (PGM) strains of H. influenzae should be taken into account when treating otitis
      media in children. OBJECTIVE: To evaluate prevalence of ss-lactamase nonproducing
      ampicillin-resistant (BLNAR) strains of Haemophilus influenzae with mutations in
      ftsI gene encoding penicillin-binding protein 3 (PBP3) among children with otitis
      media. METHODS: A total of 644 nasopharyngeal isolates of H. influenzae was
      collected from pediatric acute otitis media (AOM) patients with or without otitis
      media with effusions (OME) at the clinics of Otolaryngology-Head and Neck
      Surgery, Wakayama Medical University Hospital and six affiliated hospitals in
      Wakayama prefecture between January 1999 and December 2003. Minimal inhibitory
      concentrations (MICs) of ampicillin (AMP), cefditoren (CDN), cefdinir (CFD),
      cefaclor (CCL), cefpodoxime (CPD), and cefcapene (CFPN) were determined by the
      microbroth dilution method according to the recommendations of the National
      Committee for Clinical Laboratory Standards (NCCLS). Types of mutations in PBP3
      gene (ftsI) were evaluated by a polymerase chain reaction (PCR)-based genotyping
      method. ss-Lactamase gene (bla) was also identified by PCR. RESULTS: ss-Lactamase
      producing (BLP) strains with the bla gene were identified in 16 (2.5%) of
      isolates. PGM strains were identified in 279 (43.3%) isolates. There were 242
      (37.6%) PGM1-nonBLP strains with mutations in variable mutated locus of ftsI, 35
      (5.4%) PGM2-nonBLP strains with mutations in highly mutated locus of ftsI, 2
      (0.3%) BLP-PGM strains with mutations in ftsI and producing ss-lactamase. BLP
      nonPGM strains producing ss-lactamase without mutations in ftsI were identified
      in 14 (2.2%) isolates. MICs of PGM1-nonBLP strains to AMP were 0.5-2.0 microg/ml.
      The MIC(90) of CDN to the PGM1-nonBLP strains was lowest (0.06 microg/ml).
      Proportions of PGM1-nonBLP strains rapidly increased during 1999 to 2002 and then
      decreased in 2003. In contrast, PGM2-nonBLP strains increased in 2003.

PMID- 16428189
TI  - Expression of the gap junction proteins connexin 26 and connexin 43 in human
      middle ear cholesteatoma.
AB  - CONCLUSION: The results of this study showed upregulated expression and a change
      in localization of both connexin 43 (Cx43) and Cx26 in human middle ear
      cholesteatoma compared to those in normal retroauricular skins (RASs) and ear
      canal skins (ECSs). This suggests that perturbations of intercellular
      communication through gap junctions may be associated with the pathology of human
      cholesteatomas. OBJECTIVE: Cholesteatomas in the middle ear require intercellular
      signal exchange through gap junctions as well as intracellular signal pathways
      for the hyperproliferation and differentiation of epithelial cells. Cx is a gap
      junction protein involved in intercellular communication. The objective of this
      study was to analyze the expression and possible roles of Cx43 and Cx26 in human
      cholesteatoma compared to normal epithelium. MATERIAL AND METHODS: Ten RASs, 10
      ECSs and 10 cholesteatomas were obtained during middle ear operations.
      Immunohistochemical staining, Western blotting and reverse transcriptase
      polymerase chain reaction (RT-PCR) were used to detect Cx43 and Cx26. The
      expression patterns of Cx43 and Cx26 were also compared with that of the
      proliferation marker Ki67. RESULTS: In human cholesteatomas, Cx43 was expressed
      in whole suprabasal layers, except in the basal layer, and Cx26 was usually
      expressed in the suprabasal and basal layers. However, normal RASs showed weak
      expression of Cx43 in the upper spinosal and granular layers (with no expression
      in the basal layers) and restricted localization of Cx26 in the basal layer. The
      expression of Cx43 and Cx26 in ECSs was weak but showed similar patterns to that
      of cholesteatoma. RT-PCR and Western blotting showed that the expression of Cx43
      and Cx26 was higher in cholesteatoma than in RASs. Epithelial cells expressing
      Cx43 and Cx26 in cholesteatoma were not exactly identical to Ki67-expressing
      cells on immunohistochemical staining.

PMID- 16428190
TI  - Anti-adhesive properties of polytetrafluoroethylene (Gore-Tex) in middle ear
      surgery. An experimental study.
AB  - CONCLUSIONS: Polytetrafluoroethylene (PTFE) may represent a material that
      prevents adhesions when implanted in the middle ear. This characteristic can be
      used to improve the design of prostheses. OBJECTIVE: Prostheses in the middle ear
      have a relatively high failure rate due to extrusion, deformation and adhesion.
      Adhesion of prostheses to the walls of the tympanic cavity is the commonest cause
      of long-term hearing loss. The anti-adhesive properties of PTFE have been
      previously studied in abdominal and vascular surgery. To the best of our
      knowledge, this is the first work in which the properties of PTFE have been
      studied in the context of middle ear pathology. MATERIAL AND METHODS: In order to
      induce otitis media with effusion, 27 Wistar rats underwent a technique based on
      permanent cauterization of the pharyngeal Eustachian tube. PTFE was subsequently
      implanted in the middle ear. Rats that underwent cauterization without
      implantation and cauterization with implantation of hydroxyapatite and Plastipore
      were included as controls. RESULTS: Histopathological study of the tympanic
      bullae at 15 and 90 days after implantation demonstrated good biocompatibility of
      the PTFE implant under the analyzed conditions, with formation of a capsule
      around the material and no adhesions between the ear tissues and the prosthesis.

PMID- 16428191
TI  - Utilization of fresh human tympanic membranes for structural analysis and
      cytokeratin immunocytochemistry implementing resin techniques.
AB  - CONCLUSIONS: The results of this study have demonstrated for the first time that
      tympanic membrane (TM) structure is preserved following removal of fresh, normal
      tissue from patients undergoing surgery. Greater clarity has been demonstrated
      using resin sections than in previous studies on paraffin sections. Of particular
      note, cytokeratin (CK) immunocytochemistry was successfully performed on resin
      sections, which has not been previously reported. This may have potential
      applications for future work involving tissues that express CKs. OBJECTIVES: To
      analyse the structure of normal, fresh human TM specimens after surgical removal
      and to evaluate their CK immunocytochemistry using resin techniques, neither of
      which have been demonstrated previously. MATERIAL AND METHODS: Seven TM specimens
      were removed during surgery and then preserved in a modified Karnovsky's
      fixative. Semi-thin and thin sections were examined by means of light and
      electron microscopy, respectively. For comparison purposes, paraffin block
      embedded specimens were also sectioned. CK immunocytochemistry was performed on
      semi-thin sections using standard immunoperoxidase techniques, with expression
      being demonstrated using light microscopy. RESULTS: The three-layer architecture
      of the TM was preserved. The morphology of the TM was vastly superior in the semi
      thin resin sections than in the thicker paraffin sections. The outer, middle and
      inner layers were clearly demonstrated. The integrity of the outer epithelial
      layer was maintained, with an outer keratinizing stratum corneum and underlying
      stratum granulosum, stratum spinosum and stratum basale layers resting on the
      basal lamina. The thin inner mucosal layer was also viable, consisting of simple
      squamous or cuboidal cells. Preservation of the middle lamina propria was
      achieved, with demonstration of the outer radial and inner circular fibres. CK
      immunocytochemistry utilizing resin techniques provided excellent staining of CK
      7 and 8 in the inner layer, with positive staining of CK 5 and 10 in the outer
      layer.

PMID- 16428192
TI  - Does Helicobacter pylori colonize the nasopharynx of children and contribute to
      their middle ear disease?
AB  - OBJECTIVE: There is growing interest in studying the presence of HP in the upper
      aerodigestive tract. It was shown in several pilot studies that it colonizes the
      area, while other authors found no evidence of its presence there and a third
      group of authors believed that it had only a transient presence there. In this
      study we investigated a possible role for HP in middle ear disease in children.
      MATERIAL AND METHODS: Consecutive patients undergoing myringotomy and
      adenoidectomy for chronic otitis media with effusion or recurrent otitis media
      were enrolled. Middle ear fluids were cultured on three types of agar plate
      (Brucella + laked horse blood; Brucella + sheep blood; and chocolate). A double
      polymerase chain reaction (PCR) was run to detect urease-C and adhesion subunit
      genes. Rapid urease enzyme testing and PCR were used on the adenoid specimens.
      Parents were interviewed regarding symptoms suggestive of gastroesophageal reflux
      in their children. RESULTS: Eighteen patients were enrolled in the study (mean
      age 4.4 years; age range 3-8 years) with an equal gender distribution. All 28
      middle ear fluid cultures were negative in all 3 media. Twenty-one of the 28
      samples contained DNA, yet PCR revealed that none of them belonged to HP. Ten of
      the 13 adenoid specimens obtained were positive on rapid urease testing, but none
      on PCR. Seven of the 18 patients had at least 1 symptom suggestive of
      gastroesophageal reflux during the 6 months preceding the study but this did not
      have an impact on any of the results. CONCLUSION: There was no evidence from this
      study that Helicobacter pylori (HP) colonizes the nasopharynx of children with
      middle ear disease, whether dyspeptic or not. There is also no apparent role for
      this bacterium in middle ear pathology.

PMID- 16428193
TI  - Benign paroxysmal positioning vertigo: a long-term follow-up (6-17 years) of 125
      patients.
AB  - CONCLUSIONS: The study disclosed a few predictive factors for benign paroxysmal
      positioning vertigo (BPPV) recurrences, which are clinically relevant and
      essential for patient awareness of the often long-term course of the condition.
      OBJECTIVES: To determine the long-term recurrence rate of posterior canal BPPV
      after successful liberatory maneuvers. METHODS: A retrospective self-evaluation
      questionnaire with a structured interview was conducted 6-17 years after
      assessment of the diagnosis in 125 patients. RESULTS: The recurrence rate in
      patients with a mean follow-up of 10 years was 50%. Most recurrences (80%) were
      within the first year after treatment, irrespective of the liberatory maneuver
      applied. None of the patients observed a recurrence after a symptom-free period
      of 8 years. Recurrences were seen significantly more often in women (58% versus
      39%). The recurrence rate of patients in the seventh decade was half that of
      those in the sixth decade (p=0.0009). A history of three or more BPPV attacks
      prior to treatment indicated a higher risk of impending multiple recurrences in
      about two-thirds of the patients.

PMID- 16428194
TI  - Vestibular-evoked myogenic potentials in cochlear implant children.
AB  - CONCLUSIONS: Our results suggest that the sacculi of most children with cochlear
      implants can easily be damaged, as shown by the absence of vestibular-evoked
      myogenic potentials (VEMPs) in response to click stimuli. Also, in most of the
      children, the vestibular nerve was seemingly not stimulated by the cochlear
      implant. These results suggest that electrical stimulation at the C level can
      stimulate the cochlear nerve; however, this stimulation did not spread to the
      vestibular nerve in our children. In some children with Mondini dysplasia or
      vestibulocochlear nerve abnormality, the vestibular nerve was stimulated when the
      cochlear implant device was on, because of a VEMP response to electrical
      stimulation. OBJECTIVE: To clarify the diagnostic value of VEMPs in cochlear
      implant patients. MATERIAL AND METHODS: The click-evoked myogenic potentials of
      12 children who underwent cochlear implantation surgery were investigated. The
      latency and amplitude of the VEMP responses were measured. RESULTS: Before
      surgery, 6 of the 12 children showed normal VEMPs, 1 showed a decrease in the
      amplitude of VEMPs and five showed no VEMP response. After surgery, with the
      cochlear implant device off, 1 child showed a decreased VEMP and 11 showed no
      VEMPs. With the cochlear implant device on, four children showed VEMPs and eight
      did not.

PMID- 16428195
TI  - Intracranial vertebral artery dissection mimicking acute peripheral vertigo.
AB  - When diagnosing and treating patients with acute vertigo, the clinician must
      differentiate brain lesions from benign peripheral disorders. We here report a
      rare case of acute vertigo caused by intracranial vertebral artery dissection
      mimicking peripheral disease. A 67-year-old man presented with spontaneous
      nystagmus and moderate ataxia preceded by neck pain. No other neurological signs
      were observed, suggesting acute peripheral vertigo. However, magnetic resonance
      imaging (MRI) demonstrated a cerebellar infarction. Simultaneous magnetic
      resonance angiography (MRA) showed no flow void of the left vertebral artery and
      contrast-enhanced MRA demonstrated a double lumen sign, suggesting that vertebral
      artery dissection was a cause of infarction. The clinical course was favorable
      without anticoagulation drugs, which are sometimes contraindicated because of the
      potential risk of subarachnoid hemorrhage. Vertebral artery dissection can cause
      cerebellar infarction in patients without vascular risk factors mimicking acute
      peripheral vertigo. Careful history regarding the neck pain is important and MRA
      in combination with MRI can replace angiography in diagnosing this disorder.

PMID- 16428196
TI  - Effects of prostagladin E(2) on gel-forming mucin secretion in normal human nasal
      epithelial cells.
AB  - CONCLUSION: The findings of this study indicate that prostaglandin E(2) (PGE(2))
      induces MUC5AC gene expression and mucin secretion via the EP4 receptor in
      cultured normal human nasal epithelial cells. OBJECTIVES: Recently, PGE(2) was
      found to induce MUC5AC production via an agonist of EP2/EP4, but not EP1/EP3, in
      normal human airway epithelium. However, the receptor that mediates MUC5AC has
      not been determined. This study aimed to investigate the MUC5AC mucin gene and
      mucin secretion by PGE(2) and its receptors in cultured normal human nasal
      epithelial cells. METHODS: After treatment with PGE(2) and/or PGE(2) antagonist,
      gel-forming mucin mRNA expression was determined by reverse transcription
      polymerase chain reaction. Total mucin and MUC5AC mucin levels were measured
      using an immuno-dot blotting assay. RESULTS: PGE(2) increased only MUC5AC gene
      expression and MUC5AC mucin, but not expression of other gel-forming mucin genes.
      An EP2 receptor antagonist (AH 6809) did not suppress the PGE(2)-induced MUC5AC
      gene expression or MUC5AC mucin. However, an EP4 receptor antagonist (AH23848)
      significantly suppressed the level of PGE(2)-induced MUC5AC gene expression and
      MUC5AC mucin.

PMID- 16428197
TI  - IgE-positive plasma cells are present in adenoids of atopic children.
AB  - CONCLUSIONS: We demonstrated the presence of IgE(+) plasma cells in the adenoids
      of atopic children. Our data suggest that adenoids are capable of local
      production of IgE and support the role of adenoids as an inductive site for
      allergic reactions. OBJECTIVE: We have previously demonstrated increased numbers
      of IgE(+) cells in the adenoids of atopic children and also found support for an
      IL-4-induced class switch to IgE production in adenoids. In search of further
      evidence of adenoids being involved in IgE-mediated sensitization, we
      investigated the distribution of plasma cells and macrophages positive for IgE in
      adenoids. MATERIAL AND METHODS: Adenoid tissue from atopic and non-atopic
      children was examined using immunohistochemical markers for IgE, plasma cells
      (CD138) and macrophages (CD68). The distribution of positive cells was determined
      in the extrafollicular area and in the follicles of adenoids. Co-localization of
      IgE and CD138(+) plasma cells and CD68(+) macrophages was examined using
      immunohistochemical double-staining methods. RESULTS: Non-atopic adenoids
      contained no or very few IgE(+) cells. In contrast, IgE(+) cells were found in
      high numbers in atopic adenoids, mainly in the extrafollicular area. Higher
      numbers of IgE(+) plasma cells and IgE(+) macrophages were also found in the
      adenoids of atopic children.

PMID- 16428198
TI  - Cytokines produced by T cells in adenoid surface secretion are mainly
      downregulatory or of Th1 type.
AB  - CONCLUSIONS: T cells in adenoid surface secretion (AdSS) possess the property of
      cytokine production and are mainly downregulatory or of Th1 type. These results
      strengthen the hypothesis of an active immunological defense in AdSS. OBJECTIVES:
      Recently, we demonstrated the presence of activated T cells in AdSS. The aims of
      this study were to elucidate the ability of these T cells to produce cytokines
      and to reveal their cytokine profile. MATERIAL AND METHODS: Eight children
      subjected to adenoidectomy were enrolled. Samples of AdSS, adenoid tissue and
      peripheral blood were obtained, as well as a nasopharyngeal culture. T cells
      obtained from AdSS, adenoid tissue and peripheral blood were then cultured and
      stimulated with anti-CD3 and -CD28 for 5 days. The production of interferon (IFN)
      gamma, tumor necrosis factor (TNF)-a and IL-2, -4, -5 and -10 was then analyzed
      using flow cytometry. RESULTS: All children had T cells in AdSS capable of
      cytokine production. T cells in AdSS, adenoid tissue and peripheral blood samples
      from all children produced IFN-gamma. Of the cytokines analyzed, IFN-gamma was
      produced in the highest concentrations. In 6/8 children, T cells in AdSS also
      produced TNF-a and IL-10.

PMID- 16428199
TI  - Autogenous fat injection for glottic insufficiency: analysis of 101 cases and
      correlation with patients' self-assessment.
AB  - CONCLUSIONS: Our data confirm that fat injection (FI) is a safe, useful, thorough
      and experience-dependent procedure. It should be considered as a potential
      treatment protocol for patients with vocal fold atrophy (VFA) and sulcus
      vergeture (SVER). To increase the chances of excellent phonatory results for
      sulcus vocalis (SV) patients, our recommended surgical option is FI with fascia
      transplantation. OBJECTIVE: To investigate prognostic factors in patients with
      glottic insufficiency following FI. MATERIAL AND METHODS: The study sample
      comprised 101 patients treated for VFA (n=31), SVER (n=41) and SV (n=29). A
      retrospective analysis was performed by means of patient self-assessments,
      employing multiple logistic regressions for the four independent factors of age,
      gender, diagnosis and time-frame of surgery. RESULTS: The mean follow-up time was
      16.8 months (range 5-38 months). Immediate complications included hematoma of the
      donor site in two patients and fat extrusion at the injection site in three. The
      results of treatment were "excellent" in 48.4% (15/31) of VFA cases, 43.9%
      (18/41) of SVER cases and 20.7% (6/29) of SV cases, with 19.4% (6/31), 24.4%
      (10/41) and 55.2% (16/29), respectively reporting improvement and 32.3% (10/31),
      31.7% (13/41) and 24.1% (7/29), respectively reporting no improvement. Disease
      type was determined to have a significant bearing (p=0.025) on treatment
      effectiveness and patients operated on most recently were shown to have a 4.3
      times greater chance of achieving successful results (p<0.01). Multiple logistic
      regression analysis indicated that VFA and SVER sufferers (as compared to those
      with SV) and men (as opposed to women) were more likely to achieve an "excellent"
      result: 3.4, 3.3 and 3.6 times, respectively.

PMID- 16428200
TI  - High nuclear expression of the apoptosis inhibitor protein survivin is associated
      with disease recurrence and poor prognosis in laryngeal basaloid squamous cell
      carcinoma.
AB  - CONCLUSION: Nuclear expression of survivin should be studied as a promising
      marker of higher-risk laryngeal basaloid squamous cell carcinomas (BSCCs), which
      can then be treated more aggressively and followed more closely. OBJECTIVE: BSCC
      is an uncommon bimorphic variant of SCC. The hypothesized greater aggressiveness
      and poorer prognosis of head and neck BSCC compared to SCC are still under
      debate. The regulation of apoptotic cell death has a profound effect on the
      pathogenesis and progression of malignancies. Survivin is the smallest member of
      the inhibitor of apoptosis gene family. The aim of this study was to investigate
      for the first time the expression of the inhibitor of apoptosis protein survivin
      in laryngeal BSCCs and their neck lymph node metastases and to compare the
      results with those obtained with conventional SCCs. MATERIAL AND METHODS:
      Immunoreactivity to survivin was determined in nine laryngeal BSCCs and nine site
      and stage-matched SCCs. RESULTS: A nuclear subcellular localization of survivin
      dominated in both primary laryngeal BSCCs and SCCs and in their lymph node
      metastases. There was no significant difference in mean survivin expression
      between primary laryngeal BSCCs (25.1%) and SCCs (25.6%) (p=0.86). Nuclear
      survivin expression was significantly higher in BSCCs associated with disease
      recurrence and poor prognosis (p=0.02).

PMID- 16428201
TI  - Improvement of the radial forearm donor site by compression with hydrocolloid
      dressing and adhesive sponge.
AB  - CONCLUSIONS: With our method, general improvement is obtained as compared with
      traditional split-thickness skin grafting of the radial forearm flap donor site.
      As our method is simple and easy, the same results can be obtained wherever and
      by whomever it is performed. OBJECTIVE: The radial forearm flap is associated
      with complications of graft take and a poor aesthetic appearance despite its
      usefulness in reconstructing the oral cavity and oropharynx. We describe a simple
      technique for improvement of the radial forearm donor site. PATIENTS AND METHODS:
      We studied 12 patients who underwent reconstruction with radial forearm free
      flaps following resection of oral or oropharyngeal tumors. We covered the donor
      site defect using traditional split-thickness skin grafts and performed aftercare
      with a hydrocolloid dressing and an adhesive sponge to retain moisture and apply
      compression. After the treatment series, color matching, texture matching,
      depressive deformity, and hypertrophic scar were evaluated. RESULTS: The results
      of comprehensive evaluation of the two patients with premature discontinuation of
      compression were good. One patient was assigned only 1 point for hypertrophic
      scar, and another only 1 point for color match. The evaluation of the other 10
      patients was excellent.

PMID- 16428202
TI  - Bulky cervical liposarcoma associated with sleep apnea syndrome.
AB  - Sarcomas of the head and neck are relatively infrequent tumors. Liposarcomas
      represent 10-16% of all soft tissue sarcomas and <5% of them arise from the head
      and neck. The retropharyngeal area is rarely involved. We present the case of a
      middle-aged male with clinical symptoms of sleep apnea. A fiber-optic examination
      revealed a soft submucosal lesion compressing the posterior pharyngeal wall, with
      partial obstruction of the airway tract. CT showed a large heterogeneous
      prevertebral mass (6 x 20 cm(2)) occupying the posterior mediastinum. A transoral
      submucosal biopsy was performed. Histological findings were compatible with a low
      grade liposarcoma. The mass was removed in monoblock using a classical
      laterocervical neck incision. The surgical specimen weighed 500 g. After 24
      months of follow-up no signs of tumor recurrence or sleep apnea syndrome were
      noted.

PMID- 16428203
TI  - Histopathological parameters of recurrence and malignant transformation in
      sinonasal inverted papilloma.
AB  - CONCLUSIONS: A combination of parameters may be useful in predicting the clinical
      course of squamous cell carcinoma in inverted papilloma (IP). In particular, the
      parameters hyperkeratosis, squamous epithelial hyperplasia and high mitotic index
      were negative prognostic indicators. OBJECTIVE: To define histopathological
      parameters which could predict the recurrence and development of squamous cell
      carcinoma in IP. MATERIAL AND METHODS: We analyzed the histopathological
      characteristics of 39 cases of IP using the following parameters: site of origin
      of tumor; presence of bone invasion; presence of inflammatory polyp; ratio of
      endophytic to exophytic lesions; ratio of neoplastic epithelium to stroma;
      presence of hyperkeratosis; presence of squamous epithelial hyperplasia; mitotic
      index; number of mucin globules; and number of eosinophils. RESULTS: Malignancy
      was related to the presence of bone invasion (p=0.039), the absence of
      inflammatory polyp (p=0.033), increase in the ratio neoplastic epithelium:stroma
      (p=0.037), increase in hyperkeratosis (p=0.030), the presence of squamous
      epithelial hyperplasia (p=0.044), increase in the mitotic index (p=0.029) and a
      decrease in the number of eosinophils (p=0.037). Multiple recurrences (without
      malignancy) were related to frontal sinus origin (p=0.042), increase in
      hyperkeratosis (p=0.041), the presence of squamous epithelial hyperplasia
      (p=0.044) and increase in the mitotic index (p=0.031). Clinically benign behavior
      was related to the presence of inflammatory polyp (p=0.010) and the absence of
      hyperkeratosis (p=0.008).

PMID- 16428204
TI  - A case of major salivary gland agenesis.
AB  - Major salivary gland agenesis is a rare disorder and only a few instances of the
      condition have been reported. The number of absent salivary glands and the degree
      of associated xerostomia vary between individuals. Salivary gland agenesis can
      cause profound xerostomia in children and there may be oral and upper respiratory
      tract sequelae, such as dental caries, candidiasis, ascending sialadenitis,
      laryngitis and pharyngitis. Salivary gland aplasia may be associated with other
      ectodermal defects, particularly abnormalities of the lacrimal apparatus. We
      report on the first observation of major salivary gland agenesis in South Korea.
      A child with xerostomia should be appropriately investigated and diagnosed, and
      careful attention should be paid to the prevention and treatment of sequelae.

PMID- 16428205
TI  - Phenol as a topical anaesthetic agent for myringotomy.

PMID- 16428207
TI  - Ten years' experience of free flaps for breast reconstruction in a Danish
      microsurgical centre: an audit.
AB  - We have done a total of 292 breast reconstructions using a free flap over a
      period of 10 years (1994-2003). During the last five years the number of deep
      inferior epigastric perforator (DIEP) flaps has increased. However, to secure an
      optimal blood supply we still use a muscle-sparing transverse rectus abdominis
      musculocutaneous (TRAM) flap sometimes. Our results with the two flaps were
      identical as far as operating time and length of hospital stay were concerned,
      but the DIEP flap has less donor site morbidity. Our results are influenced by
      our selection of patients and our technique but we think that muscle-sparing TRAM
      flaps may be used as an alternative to DIEP flaps.

PMID- 16428206
TI  - The effects of anti-P-selectin antibody on leucocyte activity related to
      cigarette smoke in rats.
AB  - Nicotine-induced expression of P-selectin is implicated in endothelial cell
      damage related to smoking. Thirty male Sprague-Dawley rats were divided into
      three groups: two experimental and one control. Both experimental groups were
      exposed to cigarette smoke for four weeks, but one group was also given anti-P
      selectin antibody (100 microg IgG per 100 g body weight) intravenously. Rolling
      and adhesion leucocytes within the microcirculation of the cremaster muscle were
      measured. The urine cotinine concentrations of rats exposed to smoke were 612
      ng/ml higher than those of non-smokers. Both rolling and adherent leucocytes were
      highest and steady in the group given anti-P-selectin antibody at about 50 and
      10, respectively. There was a significant drop in both rolling and adherent
      leucocytes (31 to 4 and 5 to 2) after the anti-P-selectin antibody had been
      given. However, this effect was short-lived as both increased above those at 35
      minutes by 120 minutes (p<0.001). The increase in leucocyte rolling and adherence
      caused by smoking can be lowered by giving anti-P-selectin antibody. The
      effective period in rats was two hours, with the maximal effect one hour after
      injection.

PMID- 16428208
TI  - Role of the size of the pedicle in reduction mammaplasty.
AB  - We retrospectively evaluated the lateral pedicle technique for reduction
      mammaplasty. One hundred and one women were reviewed, using a questionnaire.
      Fifty-nine of these women were tested 5-7 years postoperatively. All patients
      were operated on using a large, thick lateral pedicle. There were 10 major
      complications. Adipose women with larger breasts (hypertrophy or gigantomastia)
      had no more complications than the smaller reductions. In those who had larger
      resections, only those with a combination of risk factors developed complications
      (old age, heavy smoking, and obesity). There were other reasons for complications
      in those who had smaller reductions. Twenty-four patients were relieved of pain
      and 83 reported improvement in their work and social life after operation. There
      were 47 women who were very satisfied and 33 who were satisfied with the results
      (total 80/101).

PMID- 16428209
TI  - Effects of bilateral breast reduction on anxiety and depression: results of a
      prospective randomised trial.
AB  - We assessed the effects of bilateral breast reduction on anxiety and depression
      in women with mammary hypertrophy (macromastia). Seventy-three consecutive women
      referred for consideration for breast reduction were recruited. They were
      randomised to have either early operation (within six weeks of initial
      assessment) or delayed operation (within six months of recruitment). The Hospital
      Anxiety and Depression Score was given before randomisation and four months
      later. All 73 patients completed the study. The mean (SD) age was 39 (12) years.
      The groups were matched for age, smoking, social class, and educational
      achievement. There were highly significant improvements (p<0.001) in symptoms of
      anxiety and depression. Reduction mammaplasty significantly improved symptoms of
      clinical depression in women with macromastia.

PMID- 16428210
TI  - Sentinel node biopsy in cutaneous melanoma.
AB  - Status of the regional lymph nodes is a strong prognostic factor in patients with
      cutaneous malignant melanoma (CMM) and can be assessed by sentinel lymph node
      biopsy (SLNB). We present our technique of preoperative lymphatic mapping and
      intraoperative vital dye and handheld gamma probe. Our results and three years
      follow-up of its routine use in 198 patients with verified primary CMM are
      presented. Median follow-up time was 24 months (range 1-47). Metastatic regional
      lymph node disease was found by SLNB in 61 patients (31%) and additional
      metastatic nodes were found by formal node dissection in 30% of these cases.
      Complications were relatively mild but included one case of lymphoedema in a node
      negative patient. By follow-up, 13% had developed a recurrence including 26% of
      node positive patients and 8% of node negative patients. Mortality was also
      substantially higher in node positive cases with 18% dying in the follow-up
      period and 3% in the node negative group. The SLNB procedure was associated with
      a false negative rate of 8%. Using the presented technique, we found that SLNB
      was a useful procedure for staging patients with CMM and for selecting patients
      for more extensive metastatic screening and inclusion in trials of adjuvant
      treatments.

PMID- 16428211
TI  - Reconstruction method with a newly-designed bilobed flap after excision of
      tumours of the skin.
AB  - We have devised a bilobed skin flap for reconstruction after excision of small
      skin tumours. The sutured part serves as a zig-zag that leads to only slight
      postoperative contracture of the scar. The rotation centre of the flap is nearer
      to the affected area than other conventional bilobed flaps, resulting in less dog
      ear deformity and distortion of tissue.

PMID- 16428213
TI  - Compartmental reconstruction for de Quervain stenosing tenosynovitis.
AB  - We describe a new surgical technique for the treatment of de Quervain
      tenosynovitis, which consists of lengthening the first dorsal compartment without
      disruption of continuity and without using a suture. Our results in 12 wrists
      operated on in 10 patients indicated complete relief of symptoms. The advantages
      of the technique include: simplicity, restoration of normal anatomy, and
      prevention of complications (scarring, adhesions, and subluxation of tendons).

PMID- 16428212
TI  - Carpal tunnel syndrome during pregnancy.
AB  - Carpal tunnel syndrome is common during pregnancy. The symptoms usually disappear
      after delivery, but how soon has not been established. Thirty pregnant women with
      the syndrome reported to us the degree of pain in their hands every week before,
      and daily after, delivery. Pain was graded on a scale from 0 (none) to 10 (worst
      imaginable). The prevalence of the syndrome during pregnancy was about 2%. The
      mean pain score was 5.6 (SD 2.0) at referral and this was reduced by 1.2 (SD 2.2)
      after wearing an orthosis for a week. After this, it stayed almost unchanged
      until delivery. The score fell by half during the first week after parturition
      and by half again during the next week. The reduction in score was strongly
      correlated with loss of the weight gained during pregnancy (r = 0.97; p <0.001).
      Although symptoms may persist for some weeks after delivery, the severity
      declines quickly.

PMID- 16428214
TI  - Survival and complications are similar after Swanson and Sutter implant
      replacement of metacarpophalangeal joints in patients with rheumatoid arthritis.
AB  - We compared the survival, fracture, and deformation rates of Swanson and Sutter
      implants in a prospective series of 53 patients with rheumatoid arthritis (RA).
      Fifty-eight hands were operated on with 215 silastic implants. The Swanson group
      comprised 25 hands and 89 implants, and the Sutter group 33 and 126,
      respectively. Follow up was 58 (37-80) months. During a period of 48 months the
      survival of Swanson and Sutter prostheses did not differ significantly: 92% (95%
      CI 84% to 96%) and 97% (95% CI 92% to 99%), respectively. The fracture rate was
      high in both groups: 26 (34%) in the Swanson and 25 (26%) in the Sutter group.
      There was no significant difference between the groups in definite fracture rates
      of implants. The Sutter prosthesis appears to be at least as durable an implant
      in rheumatoid patients' metacarpophalangeal arthroplasty as the Swanson.

PMID- 16428215
TI  - Superficial basal cell carcinoma of the scalp mimicking seborrhoeic dermatitis.
AB  - Superficial basal cell carcinomas (BCC) comprise 9% to 11% of BCC, and are
      commonly found on the trunk or limbs. We report a case of a superficial BCC on
      the scalp that was misdiagnosed and treated as seborrhoeic dermatitis. Any
      erythematous plaque-type lesion of long duration must have superficial BCC
      considered in the differential diagnosis.

PMID- 16428216
TI  - Auricular teratoma: report of a case and review of rare sites.
AB  - We report a case of auricular teratoma in a 2-month-old child. We could find no
      other report of a case of auricular teratoma, although there are a few reports of
      teratomas in various other parts of the ear.

PMID- 16428217
TI  - Liposuctioned rectus abdominis myocutaneous flap to cover a vulval skin defect.
AB  - A woman with genital Paget disease had a reconstruction with a rectus abdominis
      myocutaneous flap after primary liposuction during operation. The patient
      recovered satisfactorily.

PMID- 16428218
TI  - Pros and cons of medicalization: the example of trauma.

PMID- 16428219
TI  - Memory performance in dyslexic male juvenile delinquents convicted of severe
      offences does not differ from that in dyslexic male junior college students.
AB  - BACKGROUND: There are different research approaches regarding the causes and
      possible overrepresentation of dyslexia in criminals. One approach focuses on
      sociological explanations such as under-stimulation at home, while another
      focuses on the importance of cognitive neurobiological dysfunctions. In several
      studies, poor memory for digits and poor verbal learning ability have been found
      in non-criminal dyslexics. AIM: To compare memory performance in two groups of
      dyslexics, namely, juvenile delinquents and junior college students, in order to
      discuss their dyslexic problems in the light of sociocultural and cognitive
      neurobiological approaches. PARTICIPANTS: Two groups of male adolescent
      dyslexics: 11 juvenile delinquents (mean age 18.55 years, SD = 2.07), all of them
      convicted for severe offences, and 11 junior college students (mean age 17.09
      years, SD = 0.83). RESULTS: Matched-samples t-tests indicate that there is no
      difference in memory performance between the two different groups of dyslexics,
      which supports the accuracy of the diagnoses of dyslexia in the group of juvenile
      delinquents. CONCLUSIONS: The present results show that the memory performance of
      dyslexic juvenile delinquents does not differ from that of dyslexic junior
      college students. A sociocultural approach, therefore, cannot plausibly explain
      the high prevalence of reading and writing difficulties among juvenile
      delinquents.

PMID- 16428220
TI  - Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar
      patients: impact of past episodes.
AB  - Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many
      neuropsychiatric disorders. NO level was found high in acute manic inpatients. In
      this study, we aimed to assess NO level and activity of the antioxidant enzyme,
      superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients
      with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were
      included in this study. A semi-structured form was used to note social,
      demographic and clinical parameters of the patients. NO level and SOD activity
      were studied in the serum samples obtained from the patients and controls. The
      mean serum NO level in BD was significantly higher than in controls. Mean serum
      SOD activity was found to be elevated in patients with BD compared to controls.
      Total number of the manic episodes correlated with NO levels, but not with SOD
      activity. In conclusion, the number of manic episodes is positively associated
      with NO levels. NO and SOD appear to have a pathophysiological role in BD,
      especially in Type I euthymic phase, and may be considered an available trait
      marker for BD.

PMID- 16428221
TI  - Cerebral vasculitis following oral methylphenidate intake in an adult: a case
      report.
AB  - Methylphenidate is structurally and functionally similar to amphetamine. Cerebral
      vasculitis associated with amphetamine abuse is well documented, and in rare
      cases ischaemic stroke has been reported after methylphenidate intake in
      children. We report the case of a 63-year-old female who was treated with
      methylphenidate due to hyperactivity and suffered from multiple ischaemic
      strokes. We consider drug-induced cerebral vasculitis as the most likely cause of
      recurrent ischaemic strokes in the absence of any pathological findings during
      the diagnostic work-up. We conclude that methylphenidate mediated vasculitis
      should be considered in patients with neurological symptoms and a history of
      methylphenidate therapy. This potential side-effect, though very rare, represents
      one more reason to be very restrictive in the use of methylphenidate.

PMID- 16428222
TI  - Prenatal over-androgenisation, gender identity disorders and infertility.

PMID- 16428225
TI  - Australian adults' production of /n/: an EPG investigation.
AB  - Images of tongue/palate contact for the nasal phoneme /n/ were created using the
      electropalatograph (EPG). Seven typical Australian adults with no history of
      hearing or communication difficulty produced syllables containing /n/ paired with
      five vowels. The majority of productions were symmetrical had contact with the
      alveolar ridge, and lateral bracing along the sides of the palate; however, there
      were notable exceptions. There was a wide range of inter- and intra-participant
      variation in the visual representations of the maximum point of contact as well
      as in measures of total palate contact (TPC) and centre of gravity (COG). It is
      suggested that when describing acceptable production of /n/ a range of
      tongue/palate contact patterns are provided.

PMID- 16428224
TI  - A comparison of English reading passages for elicitation of speech samples from
      clinical populations.
AB  - Oral reading passages are often used to elicit speech samples from clinical
      populations. Few objective guidelines exist, however, to guide one's selection
      from among the many existing passages. Therefore, this study was undertaken to
      describe phonetic, lexical, and structural characteristics of 15 oral reading
      passages. The passages differed markedly in the demands that they placed upon the
      speaker (i.e., length and complexity), as well as the adequacy of the phonetic
      sample.

PMID- 16428226
TI  - Metrical/syllabic factors in English allophony: dark /l/.
AB  - This paper presents a single-subject case study illustrating the need to closely
      examine effects of dialect from syllable position on l-colouring, and the effects
      of domain-initial strengthening in General American English. Most investigators
      report lighter /l/ tokens in syllable onsets and darker tokens in coda positions
      in isolated words. The present study demonstrates an enhanced darkened onset /l/
      in front vowel prosodic word (PW) boundaries, but lighter codas at PW-internal
      boundaries. We address the importance for clinicians of recognizing the impact of
      prosody on restructuring syntactic boundaries and its consequent effects on /l/
      articulation.

PMID- 16428227
TI  - Distributional and stylistic variation in /r/-misarticulations: a case study.
AB  - This article describes the case of a client who displayed some interesting
      patterns of realization of the target English phoneme /r/. These varied according
      to both distribution within the word, and style of utterance. We speculate as to
      the cause of some of these forms, and on possible therapy strategies.

PMID- 16428228
TI  - Clinical use of AEVP- and AERP-measures in childhood speech disorders.
AB  - It has long been recognized that from the first months of life auditory
      perception plays a crucial role in speech and language development. Only in
      recent years, however, is the precise mechanism of auditory development and its
      interaction with the acquisition of speech and language beginning to be
      systematically revealed. This paper presents the results of a series of studies
      exploring the relevance of electrophysiological measurements for the objective
      diagnosis of children with language and speech disorders. In the first,
      retrospective, study, an inventory was made of clinical neurological,
      neuropsychological, logopedic and neurophysiological findings obtained from 43
      children referred to the Paediatric Neurology Centre for the diagnosis of their
      speech and language deficits. Neurophysiological abnormalities were found in 95%
      of these children, among these deviant auditory evoked potentials (AEVPs). The
      second study demonstrated developmental trends in the waveform of the cortical
      AEVPs up to age 6 years; the implications for longitudinal studies are discussed.
      Preliminary results from the third study show emerging differences in auditory
      event-related potentials (AERPs) for young children who are at risk for
      developmental dyslexia based on their family history. These findings underscore
      the clinical usefulness of neurophysiological measures for the diagnosis of
      speech-language disorders. Clinical protocols are further developed and tested.

PMID- 16428229
TI  - Acoustic analysis of vowels following glossectomy.
AB  - This study examined the acoustic characteristics of vowels produced by speakers
      with partial glossectomy. Acoustic variables investigated included first formant
      (F1) frequency, second formant (F2) frequency, F1 range, F2 range and vowel space
      area. Data from the speakers with partial glossectomy were compared with age- and
      gender-matched controls. Results indicated no significant group difference in the
      mean F1 values and ranges. The speakers with partial glossectomy exhibited
      significantly lower mean F2 values for the vowel /i/, and restricted F2 ranges,
      when compared with the control speakers. These data suggest a limited range of
      lingual movement along the anterior-posterior dimension for vowel production. The
      significantly smaller vowel space areas for the speakers with glossectomy
      supported the hypothesis of vowel formant centralization. Two acoustic measures,
      vowel space area and F2 range, had a positive correlation with vowel
      intelligibility scores. F2 range could serve as a sensitive correlate of vowel
      intelligibility for speakers with partial glossectomy.

PMID- 16428230
TI  - Speech rate effects upon intelligibility and acceptability of dysarthric speech.
AB  - Sentences recorded by four speakers with dysarthria and two control speakers were
      presented to listeners at three different rates: habitual, a 30% slower rate and
      a 30% higher rate. Rate changes were made by digitally manipulating the habitual
      sentences. Thirty young normal adult listeners rated the sentences for
      intelligibility (per cent correct words) and acceptability (via 9-point equal
      interval scale ranging from "terrible" through "excellent"). Intelligibility for
      each speaker remained unchanged across rate changes. Acceptability improved as
      rates increased for the two more intelligible impaired speakers. For the less
      intelligible impaired speakers, ratings were better and similar for the habitual
      and fast speaking rate conditions. Results are discussed in terms of the
      objective nature of intelligibility ratings vs. the subjective ratings of
      acceptability.

PMID- 16428231
TI  - Automatic speech recognition and training for severely dysarthric users of
      assistive technology: the STARDUST project.
AB  - The STARDUST project developed robust computer speech recognizers for use by
      eight people with severe dysarthria and concomitant physical disability to access
      assistive technologies. Independent computer speech recognizers trained with
      normal speech are of limited functional use by those with severe dysarthria due
      to limited and inconsistent proximity to "normal" articulatory patterns. Severe
      dysarthric output may also be characterized by a small mass of distinguishable
      phonetic tokens making the acoustic differentiation of target words difficult.
      Speaker dependent computer speech recognition using Hidden Markov Models was
      achieved by the identification of robust phonetic elements within the individual
      speaker output patterns. A new system of speech training using computer generated
      visual and auditory feedback reduced the inconsistent production of key phonetic
      tokens over time.

PMID- 16428232
TI  - An atypical case of Foreign Accent Syndrome.
AB  - A new case of Foreign Accent Syndrome is described. This American woman presented
      with a British- or Australian- sounding accent after stroke, which resulted in a
      lacunar infarct in the left internal capsule. The atypical etiology and apparent
      changes in lexical use are described. It is hypothesized that an abnormally tense
      vocal tract posture may account for phonetic changes in vowel quality and a
      higher average fundamental frequency.

PMID- 16428233
TI  - Same noses, different nasalance scores: data from normal subjects and cleft
      palate speakers for three systems for nasalance analysis.
AB  - Nasalance scores from the Nasometer, the NasalView and the OroNasal System were
      compared. The data was collected from 50 normal participants and 19 hypernasal
      patients with cleft palate. The Nasometer had the lowest nasalance scores for the
      non-nasal Zoo Passage and that the OroNasal System had the lowest nasalance
      scores for the Nasal Sentences. The nasalance distance was largest for the
      Nasometer and smallest for the OroNasal System. When the calculation was based on
      nasalance magnitudes, results for sensitivity ranged from 57.9% to 81.8% and
      results for specificity ranged from 62.0% to 76.0%. When the calculation was
      based on nasalance distances, results for sensitivity ranged from 84.2% to 100.0%
      and results for specificity ranged from 82.0% to 100.0%. Results suggest that
      nasalance scores from the three systems are not interchangeable. Diagnostic
      efficacy improved when the calculations were based on nasalance distances rather
      than magnitudes, but further research is warranted to corroborate these findings.

PMID- 16428234
TI  - The aging female voice: acoustic and respiratory data.
AB  - The purpose of this study was to extend understanding of the effects of aging on
      the female voice by obtaining measures of both acoustic and respiratory-based
      performance in groups of 18-30, 40-49, 50-59, 60-69, and 70-79-year-old subjects.
      Acoustic measures of speaking fundamental frequency (SFF), pitch sigma, jitter,
      shimmer, and signal-to-noise ratio, as well as respiratory-based measures of
      vital capacity (VC), maximum phonation time (MPT), and phonation quotient (PQ)
      were obtained. Results indicated that the aging groups differed significantly in
      terms of SFF, pitch sigma, MPT, and VC. In addition, discriminant function
      analysis was used to classify subjects into age group via a three-variable model
      consisting of VC, SFF, and pitch sigma (84% accuracy), and into pre- vs. post
      menopausal status via a two-variable model consisting of VC and pitch sigma (92%
      accuracy). It appears that declinations in the respiratory and laryngeal
      mechanisms may occur simultaneously in the aging female.

PMID- 16428235
TI  - The clinical utility of the soft phonation index.
AB  - This paper investigates the applicability of the soft phonation index (SPI) as an
      indicator of vocal fold adduction. The SPI is one of 33 acoustic parameters
      calculated and displayed from a single vocalization by the multi-dimensional
      voice program (MDVP). A review of pertinent literature revealed that while
      increased values of SPI are presumed to be associated with incomplete adduction
      of the vocal folds, results should be interpreted cautiously as the index has not
      been sufficiently studied. The purpose of this pilot study was to determine how
      consistently SPI tracks systematic changes in vocal fold adduction. Samples of
      normal, breathy and pressed phonation produced by female speakers were analysed.
      As predicted, a significant increase in SPI for breathy productions was
      demonstrated. However, increases in SPI were also noted for pressed phonation.
      Possible explanations and implications for clinical application are discussed.

PMID- 16428236
TI  - A quantitative and qualitative evaluation of an automatic occlusion device for
      tracheoesophageal speech: the Provox FreeHands HME.
AB  - This study aimed to evaluate a new automatic tracheostoma valve: the Provox
      FreeHands HME (manufactured by Atos Medical AB, Sweden). Data from four
      laryngectomee participants using automatic and also manual occlusion were
      subjected to acoustic and perceptual analysis. The main results were a
      significant decrease, from the manual to automatic occlusion condition, in
      maximum phonation time, mean intensity of read speech and percentage pause time.
      There was an increase in random noise in the speech signal and a significant
      increase in extraneous noise caused by the device. Perceptual analysis revealed
      no clear functional impact of these differences. Data from a questionnaire and
      diary suggested the main advantage of automatic occlusion was the freedom to
      speak while performing manual tasks. The principal disadvantage appeared to be a
      decrease in base-plate seal duration. The results suggest that, for some clients,
      the FreeHands valve is a useful option for use alongside manual occlusion.

PMID- 16428238
TI  - Speech adaptation to a self-inflicted cosmetic tongue split: perceptual and
      ultrasonographic analysis.
AB  - In the cosmetic tongue split operation, the anterior tongue blade is split along
      the midline of the tongue. The goal of this case study was to obtain preliminary
      data on speech and tongue motility in a participant who had performed this
      operation on himself. The participant underwent an articulation test and a tongue
      motility assessment, as well as an ultrasound examination. Tongue motility was
      mildly reduced as a result of tissue scarring. Speech was rated to be highly
      intelligible and acceptable by 4 raters, although 2 raters noticed slight
      distortions of the sibilants /s/ and /z/. The 3-dimensional ultrasound
      demonstrated that the synergy of the 2 sides of the tongue was preserved and that
      the patient compensated for the tongue split with increased medio-lateral
      compression of the two sides of the tongue. It is concluded that the tongue split
      procedure did not significantly affect the participant's speech intelligibility
      and tongue motility.

PMID- 16428237
TI  - Voice and speech after laryngectomy.
AB  - The aim of the investigation is to compare voice and speech quality in alaryngeal
      patients using esophageal speech (ESOP, eight subjects), electroacoustical speech
      aid (EACA, six subjects) and tracheoesophageal voice prosthesis (TEVP, three
      subjects). The subjects reading a short story were recorded in the sound-proof
      booth and the speech samples were acoustically analysed. Speech sound production
      was judged by 15 students of phonetics. The following variables were considered:
      (1) voice quality: fo, jitter, shimmer and harmonic-to-noise ratio, (2) speech
      sound production: number of recognized VCV syllables, and (3) temporal
      organization of speech: duration of the phonetic block, number of syllables in
      the phonetic block, rate of speech, rate of articulation and number of syllables
      in the longest phonetic block. The results showed that nearly normal air-stream
      source (lungs) in speech production of speakers with tracheoesophageal prosthesis
      significantly contributed to the speech timing and speech intelligibility of the
      alaryngeal speakers.

PMID- 16428239
TI  - Voice and pronunciation of cochlear implant speakers.
AB  - Patients with cochlear implants have the ability to exercise auditory control
      over their own speech production and over the speech of others, which is
      important for the development of speech control. In the present investigation
      three groups of 10 subjects were compared. The groups comprised: (1) cochlear
      implant users, (2) profoundly deaf using traditional hearing aids, and (3)
      hearing controls. The subjects in three groups were matched in age. While
      repeating after a model the subjects were recorded and the following linguistic
      voice variables were analysed: (1) vowel formant space, (2) voice vs. voiceless
      difference, (3) closure duration and VOT, (4) word accent production, (5)
      sentence stress production, (6) voice quality, (7) pronunciation quality.
      Acoustic analysis and perceptual assessment by phoneticians showed that in great
      majority of variables, subjects with cochlear implants performed better than the
      profoundly deaf subjects with traditional hearing-aids.

PMID- 16428240
TI  - Speech perception of children with cochlear implants and children with
      traditional hearing aids.
AB  - The aim of the study was to analyse speech perception of children with cochlear
      implants (N = 29) and children fitted with traditional hearing aids (N = 20). One
      and two-syllable words were presented auditorily in a forced choice minimal-pair
      discrimination task. The children repeated the word and pointed to the
      appropriate picture presented on computer screen. The words were minimal pairs
      with respect to voicing or place of articulation in stops and fricatives; among
      affricates the minimal pairs included the most frequently substituted fricatives
      and stops in addition to voicing and place of articulation. Vowel discrimination
      was tested in minimal pairs and in nonsense words differing only in the vowel.
      Unaided, all children were profoundly hearing impaired and were included in
      auditory-oral therapy (Verbotonal method). The smallest differences between the
      groups were found for stops and vowels, and the largest for fricatives and
      affricates. The implanted children were significantly more successful.

PMID- 16428241
TI  - High expression of antioxidant proteins in dendritic cells: possible implications
      in atherosclerosis.
AB  - Dendritic cells (DCs) display the unique ability to activate naive T cells and to
      initiate primary T cell responses revealed in DC-T cell alloreactions. DCs
      frequently operate under stress conditions. Oxidative stress enhances the
      production of inflammatory cytokines by DCs. We performed a proteomic analysis to
      see which major changes occur, at the protein expression level, during DC
      differentiation and maturation. Comparative two-dimensional gel analysis of the
      monocyte, immature DC, and mature DC stages was performed. Manganese superoxide
      dismutase (Mn-SOD) reached 0.7% of the gel-displayed proteins at the mature DC
      stage. This important amount of Mn-SOD is a primary antioxidant defense system
      against superoxide radicals, but its product, H(2)O(2), is also deleterious for
      cells. Peroxiredoxin (Prx) enzymes play an important role in eliminating such
      peroxide. Prx1 expression level continuously increased during DC differentiation
      and maturation, whereas Prx6 continuously decreased, and Prx2 peaked at the
      immature DC stage. As a consequence, DCs were more resistant than monocytes to
      apoptosis induced by high amounts of oxidized low density lipoproteins containing
      toxic organic peroxides and hydrogen peroxide. Furthermore DC-stimulated T cells
      produced high levels of receptor activator of nuclear factor kappaB ligand, a
      chemotactic and survival factor for monocytes and DCs. This study provides
      insights into the original ability of DCs to express very high levels of
      antioxidant enzymes such as Mn-SOD and Prx1, to detoxify oxidized low density
      lipoproteins, and to induce high levels of receptor activator of nuclear factor
      kappaB ligand by the T cells they activate and further emphasizes the role that
      DCs might play in atherosclerosis, a pathology recognized as a chronic
      inflammatory disorder.

PMID- 16428243
TI  - Non-adherence to endocrine therapy for breast cancer.

PMID- 16428244
TI  - On prejudice and facts and choices.

PMID- 16428245
TI  - The Plasmodium selenoproteome.
AB  - The use of selenocysteine (Sec) as the 21st amino acid in the genetic code has
      been described in all three major domains of life. However, within eukaryotes,
      selenoproteins are only known in animals and algae. In this study, we
      characterized selenoproteomes and Sec insertion systems in protozoan Apicomplexa
      parasites. We found that among these organisms, Plasmodium and Toxoplasma
      utilized Sec, whereas Cryptosporidium did not. However, Plasmodium had no
      homologs of known selenoproteins. By searching computationally for evolutionarily
      conserved selenocysteine insertion sequence (SECIS) elements, which are RNA
      structures involved in Sec insertion, we identified four unique Plasmodium
      falciparum selenoprotein genes. These selenoproteins were incorrectly annotated
      in PlasmoDB, were conserved in other Plasmodia and had no detectable homologs in
      other species. We provide evidence that two Plasmodium SECIS elements supported
      Sec insertion into parasite and endogenous selenoproteins when they were
      expressed in mammalian cells, demonstrating that the Plasmodium SECIS elements
      are functional and indicating conservation of Sec insertion between Apicomplexa
      and animals. Dependence of the plasmodial parasites on selenium suggests possible
      strategies for antimalarial drug development.

PMID- 16428247
TI  - Structure-function analysis of the kinase-CPD domain of yeast tRNA ligase (Trl1)
      and requirements for complementation of tRNA splicing by a plant Trl1 homolog.
AB  - Trl1 is an essential 827 amino acid enzyme that executes the end-healing and end
      sealing steps of tRNA splicing in Saccharomyces cerevisiae. Trl1 consists of two
      domains--an N-terminal ligase component and a C-terminal 5'-kinase/2',3'-cyclic
      phosphodiesterase (CPD) component--that can function in tRNA splicing in vivo
      when expressed as separate polypeptides. To understand the structural
      requirements for the kinase-CPD domain, we performed an alanine scan of 30 amino
      acids that are conserved in Trl1 homologs from other fungi. We thereby identified
      four residues (Arg463, His515, Thr675 and Glu741) as essential for activity in
      vivo. Structure-function relationships at these positions, and at four essential
      or conditionally essential residues defined previously (Asp425, Arg511, His673
      and His777), were clarified by introducing conservative substitutions.
      Biochemical analysis showed that lethal mutations of Asp425, Arg463, Arg511 and
      His515 in the kinase module abolished polynucleotide kinase activity in vitro. We
      report that a recently cloned 1104 amino acid Arabidopsis RNA ligase functions in
      lieu of yeast Trl1 in vivo and identify essential side chains in the ligase,
      kinase and CPD modules of the plant enzyme. The plant ligase, like yeast Trl1 but
      unlike T4 RNA ligase 1, requires a 2'-PO4 end for tRNA splicing in vivo.

PMID- 16428248
TI  - Microarray-based DNA methylation profiling: technology and applications.
AB  - This work is dedicated to the development of a technology for unbiased, high
      throughput DNA methylation profiling of large genomic regions. In this method,
      unmethylated and methylated DNA fractions are enriched using a series of
      treatments with methylation sensitive restriction enzymes, and interrogated on
      microarrays. We have investigated various aspects of the technology including its
      replicability, informativeness, sensitivity and optimal PCR conditions using
      microarrays containing oligonucleotides representing 100 kb of genomic DNA
      derived from the chromosome 22 COMT region in addition to 12 192 element CpG
      island microarrays. Several new aspects of methylation profiling are provided,
      including the parallel identification of confounding effects of DNA sequence
      variation, the description of the principles of microarray design for epigenomic
      studies and the optimal choice of methylation sensitive restriction enzymes. We
      also demonstrate the advantages of using the unmethylated DNA fraction versus the
      methylated one, which substantially improve the chances of detecting DNA
      methylation differences. We applied this methodology for fine-mapping of
      methylation patterns of chromosomes 21 and 22 in eight individuals using tiling
      microarrays consisting of over 340 000 oligonucleotide probe pairs. The
      principles developed in this work will help to make epigenetic profiling of the
      entire human genome a routine procedure.

PMID- 16428246
TI  - Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of
      telomeres during senescence.
AB  - RecQ DNA helicases, including yeast Sgs1p and the human Werner and Bloom syndrome
      proteins, participate in telomere biology, but the underlying mechanisms are not
      fully understood. Here, we explore the protein sequences and genetic interactors
      of Sgs1p that function to slow the senescence of telomerase (tlc1) mutants. We
      find that the S-phase checkpoint function of Sgs1p is dispensable for preventing
      rapid senescence, but that Sgs1p sequences required for homologous recombination,
      including the helicase domain and topoisomerase III interaction domain, are
      essential. sgs1 and rad52 mutations are epistatic during senescence, indicating
      that Sgs1p participates in a RAD52-dependent recombinational pathway of telomere
      maintenance. Several mutations that are synthetically lethal with sgs1 mutation
      and which individually lead to genome instability, including mus81, srs2, rrm3,
      slx1 and top1, do not speed the senescence of tlc1 mutants, indicating that the
      rapid senescence of sgs1 tlc1 mutants is not caused by generic genome
      instability. However, mutations in SLX5 or SLX8, which encode proteins that
      function together in a complex that is required for viability in sgs1 mutants, do
      speed the senescence of tlc1 mutants. These observations further define roles for
      RecQ helicases and related proteins in telomere maintenance.

PMID- 16428249
TI  - Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and
      quality of life in the Bristol helicobacter project: randomised controlled trial.
AB  - OBJECTIVE: To determine the impact of a community based Helicobacter pylori
      screening and eradication programme on the incidence of dyspepsia, resource use,
      and quality of life, including a cost consequences analysis. DESIGN: H pylori
      screening programme followed by randomised placebo controlled trial of
      eradication. SETTING: Seven general practices in southwest England. PARTICIPANTS:
      10,537 unselected people aged 20-59 years were screened for H pylori infection
      (13C urea breath test); 1558 of the 1636 participants who tested positive were
      randomised to H pylori eradication treatment or placebo, and 1539 (99%) were
      followed up for two years. INTERVENTION: Ranitidine bismuth citrate 400 mg and
      clarithromycin 500 mg twice daily for two weeks or placebo. MAIN OUTCOME
      MEASURES: Primary care consultation rates for dyspepsia (defined as epigastric
      pain) two years after randomisation, with secondary outcomes of dyspepsia
      symptoms, resource use, NHS costs, and quality of life. RESULTS: In the
      eradication group, 35% fewer participants consulted for dyspepsia over two years
      compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence
      interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer
      participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS
      costs were 84.70 pounds sterling (74.90 pounds sterling to 93.91 pounds sterling)
      greater per participant in the eradication group over two years, of which 83.40
      pounds sterling (146 dollars; 121 euro) was the cost of eradication treatment. No
      difference in quality of life existed between the two groups. CONCLUSIONS:
      Community screening and eradication of H pylori is feasible in the general
      population and led to significant reductions in the number of people who
      consulted for dyspepsia and had symptoms two years after treatment. These
      benefits have to be balanced against the costs of eradication treatment, so a
      targeted eradication strategy in dyspeptic patients may be preferable.

PMID- 16428250
TI  - Mobile phone use and risk of glioma in adults: case-control study.
AB  - OBJECTIVE: To investigate the risk of glioma in adults in relation to mobile
      phone use. DESIGN: Population based case-control study with collection of
      personal interview data. SETTING: Five areas of the United Kingdom. PARTICIPANTS:
      966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29
      February 2004 and 1716 controls randomly selected from general practitioner
      lists. MAIN OUTCOME MEASURES: Odds ratios for risk of glioma in relation to
      mobile phone use. RESULTS: The overall odds ratio for regular phone use was 0.94
      (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma
      and time since first use, lifetime years of use, and cumulative number of calls
      and hours of use. A significant excess risk for reported phone use ipsilateral to
      the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk
      (0.75, 0.61 to 0.93) for contralateral use. CONCLUSIONS: Use of a mobile phone,
      either in the short or medium term, is not associated with an increased risk of
      glioma. This is consistent with most but not all published studies. The
      complementary positive and negative risks associated with ipsilateral and
      contralateral use of the phone in relation to the side of the tumour might be due
      to recall bias.

PMID- 16428251
TI  - Food buying habits of people who buy wine or beer: cross sectional study.
AB  - OBJECTIVE: To investigate whether people who buy wine buy healthier food items
      than those who buy beer. DESIGN: Cross sectional study. SETTING: Supermarkets in
      Denmark. Data Information on number, type of item, and total charge from 3.5
      million transactions over a period of six months. RESULTS: Wine buyers bought
      more olives, fruit and vegetables, poultry, cooking oil, and low fat cheese,
      milk, and meat than beer buyers. Beer buyers bought more ready cooked dishes,
      sugar, cold cuts, chips, pork, butter or margarine, sausages, lamb, and soft
      drinks than wine buyers. CONCLUSIONS: Wine buyers made more purchases of healthy
      food items than people who buy beer.

PMID- 16428252
TI  - Chronic stress at work and the metabolic syndrome: prospective study.
AB  - OBJECTIVES: To investigate the association between stress at work and the
      metabolic syndrome. [table: see text]. DESIGN: Prospective cohort study
      investigating the association between work stress and the metabolic syndrome.
      PARTICIPANTS: 10 308 men and women, aged 35-55, employed in 20 London civil
      service departments at baseline (the Whitehall II study); follow-up was an
      average of 14 years. MAIN OUTCOME MEASURES: Work stress based on the iso-strain
      model, measured on four occasions (1985-99). Biological measures of the metabolic
      syndrome, based on the National Cholesterol Education Program definition,
      measured in 1997-9. RESULTS: A dose-response relation was found between exposure
      to work stressors over 14 years and risk of the metabolic syndrome, independent
      of other relevant risk factors. Employees with chronic work stress (three or more
      exposures) were more than twice as likely to have the syndrome than those without
      work stress (odds ratio adjusted for age and employment grade 2.25, 95%
      confidence interval 1.31 to 3.85). CONCLUSIONS: Stress at work is an important
      risk factor for the metabolic syndrome. The study provides evidence for the
      biological plausibility of the link between psychosocial stressors from everyday
      life and heart disease.

PMID- 16428253
TI  - Long term outcomes from the IMPACT randomised trial for depressed elderly
      patients in primary care.
AB  - OBJECTIVE: To determine the long term effectiveness of collaborative care
      management for depression in late life. DESIGN: Two arm, randomised, clinical
      trial; intervention one year and follow-up two years. SETTING: 18 primary care
      clinics in eight US healthcare organisations. Patients 1801 primary care patients
      aged 60 and older with major depression, dysthymia, or both. INTERVENTION:
      Patients were randomly assigned to a 12 month collaborative care intervention
      (IMPACT) or usual care for depression. Teams including a depression care manager,
      primary care doctor, and psychiatrist offered education, behavioural activation,
      antidepressants, a brief, behaviour based psychotherapy (problem solving
      treatment), and relapse prevention geared to each patient's needs and
      preferences. MAIN OUTCOME MEASURES: Interviewers, blinded to treatment
      assignment, conducted interviews in person at baseline and by telephone at each
      subsequent follow up. They measured depression (SCL-20), overall functional
      impairment and quality of life (SF-12), physical functioning (PCS-12), depression
      treatment, and satisfaction with care. RESULTS: IMPACT patients fared
      significantly (P < 0.05) better than controls regarding continuation of
      antidepressant treatment, depressive symptoms, remission of depression, physical
      functioning, quality of life, self efficacy, and satisfaction with care at 18 and
      24 months. One year after IMPACT resources were withdrawn, a significant
      difference in SCL-20 scores (0.23, P < 0.0001) favouring IMPACT patients
      remained. CONCLUSIONS: Tailored collaborative care actively engages older adults
      in treatment for depression and delivers substantial and persistent long term
      benefits. Benefits include less depression, better physical functioning, and an
      enhanced quality of life. The IMPACT model may show the way to less depression
      and healthier lives for older adults.

PMID- 16428255
TI  - Galvanic corrosion between orthodontic wires and brackets in fluoride
      mouthwashes.
AB  - The aim of this investigation was to determine the influence of fluoride in
      certain mouthwashes on the risk of corrosion through galvanic coupling of
      orthodontic wires and brackets. Two titanium alloy wires, nickel-titanium (NiTi)
      and copper-nickel-titanium (CuNiTi), and the three most commonly used brackets,
      titanium (Ti), iron-chromium-nickel (FeCrNi) and cobalt-chromium (CoCr), were
      tested in a reference solution of Fusayama-Meyer artificial saliva and in two
      commercially available fluoride (250 ppm) mouthwashes, Elmex and Meridol.
      Corrosion resistance was assessed by inductively coupled plasma-atomic emission
      spectrometry (ICP-MS), analysis of released metal ions, and a scanning electron
      microscope (SEM) study of the metal surfaces after immersion of different wire
      bracket pairs in the test solutions. The study was completed by an
      electrochemical analysis. Meridol mouthwash, which contains stannous fluoride,
      was the solution in which the NiTi wires coupled with the different brackets
      showed the highest corrosion risk, while in Elmex mouthwash, which contains
      sodium fluoride, the CuNiTi wires presented the highest corrosion risk. Such
      corrosion has two consequences: deterioration in mechanical performance of the
      wire-bracket system, which would negatively affect the final aesthetic result,
      and the risk of local allergic reactions caused by released Ni ions. The results
      suggest that mouthwashes should be prescribed according to the orthodontic
      materials used. A new type of mouthwash for use during orthodontic therapy could
      be an interesting development in this field.

PMID- 16428254
TI  - Familial aggregation of atrial fibrillation in Iceland.
AB  - AIMS: To examine the heritability of atrial fibrillation (AF) in Icelanders,
      utilizing a nationwide genealogy database and population-based data on AF. AF is
      a disorder with a high prevalence, which has been known to cluster in families,
      but the heritability of the common form has not been well defined. METHODS AND
      RESULTS: The study population included 5269 patients diagnosed since 1987 and age
      sex-matched controls randomly selected from the genealogy database. Kinship
      coefficients (KC), expressed as genealogical index of familiality (GIF = average
      KC x 100,000), were calculated before and after exclusion of relatives separated
      by one to five meiotic events. Risk ratios (RR) were calculated for first- to
      fifth-degree relatives. The average pairwise GIF among patients with AF was 15.9
      (mean GIF for controls 13.9, 95%CI = 13.3, 14.4); this declined to 15.4 (mean GIF
      for controls 13.6, 95%CI = 13.1, 14.2) after exclusion of relatives separated by
      one meiosis and to 13.7 (mean GIF for controls 12.6, 95%CI = 12.1, 13.2), 12.7
      (mean GIF for controls 11.9, 95%CI = 11.4, 12.4), and 11.3 (mean GIF for controls
      10.6, 95%CI = 10.1, 11.1) after exclusion of relatives within two, three, and
      four meioses, respectively (all P<0.00001). RRs among relative pairs also
      declined incrementally, from 1.77 in first-degree relatives to 1.36, 1.18, 1.10,
      and 1.05 in second- through fifth-degree relatives (all P<0.001), consistent with
      the declining proportion of alleles shared identically by descent. When the
      analysis was limited to subjects diagnosed with AF before the age of 60, first
      degree relatives of the AF cases were nearly five times more likely to have AF
      than the general population. CONCLUSION: AF shows strong evidence of heritability
      among unselected patients in Iceland, suggesting that there may be undiscovered
      genetic variants underlying the risk of the common form of AF.

PMID- 16428256
TI  - Self-etching primer and a non-rinse conditioner versus phosphoric acid:
      alternative methods for bonding brackets.
AB  - The objective of this study was to evaluate the effectiveness of a self-etching
      primer, Transbond Plus Self Etching Primer (TSEP, 3M Unitek), and a non-rinse
      conditioner (NRC, Dentsply DeTrey) for bonding brackets, compared with the acid
      etch technique. The brackets were bonded to extracted premolars using Transbond
      XT (3M Unitek). One of the following three conditioning protocols were used: (1)
      37 per cent phosphoric acid (n = 25), (2) TSEP (n = 25), and (3) NRC (n = 15).
      Shear bond strength (SBS) was measured with a universal testing machine. The
      adhesive remaining after debonding was determined using image analysis equipment.
      Scanning electron microscope (SEM) observations were also carried out on 12
      premolars to observe the enamel surfaces. No significant differences were
      observed in SBS between the three groups (P = 0.56). TSEP and NRC left
      significantly less adhesive on the tooth than the traditional acid-etch technique
      (P = 0.004 and P = 0.000, respectively). NRC left significantly less adhesive
      than TSEP (P = 0.001). SEM observations showed that NRC produced a less
      aggressive etch pattern than TSEP, and that the etching effect of TSEP
      approximated that of phosphoric acid.

PMID- 16428257
TI  - Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005.
      Relaxation of functional constraint on light-independent protochlorophyllide
      oxidoreductase in Thuja.
AB  - The light-independent protochlorophyllide oxidoreductase (DPOR) plays a key role
      in the ability of nonflowering plants and algae to synthesize chlorophyll in
      darkness. This enzyme consists of three subunits encoded by the chlB, chlL, and
      chlN genes in the plastid genome. Previously, we found a high nonsynonymous
      substitution rate (dN) of the chlL gene in the lineage of Thuja standishii, a
      conifer belonging to the Cupressaceae. Here we revealed that the acceleration of
      dN in the chlL occurred as well in other species of Thuja, Thuja occidentalis and
      Thuja plicata. In addition, dark-grown seedlings of T. occidentalis were found to
      exhibit a pale yellowish color, and their chlorophyll concentration was much
      lower than that of other species of Cupressaceae. The results suggested that the
      species of Thuja have lost the ability to synthesize chlorophyll in darkness, and
      the functional constraint on the DPOR would thus be expected to be relaxed in
      this genus. Therefore, we expected to find that the evolutionary rates of all
      subunits of DPOR would in this case be accelerated. Sequence analyses of the chlN
      and chlB (encoding the other subunits of DPOR) in 18 species of Cupressaceae
      revealed that the dN of the chlN gene was accelerated in Thuja as was the dN of
      the chlL gene, but the dN of the chlB gene did not appear to differ significantly
      among the species of Cupressaceae. Sequencing of reverse transcription-polymerase
      chain reaction (RT-PCR) products of these genes showed that RNA editing was rare
      and unlikely to have contributed to the acceleration. Moreover, the RT-PCR
      analysis indicated that all chl genes were still transcriptionally active in T.
      occidentalis. Based on these results, it appears that species of Thuja still bear
      the DPOR protein, although the enzyme has lost its activity because of
      nonsynonymous mutations of some of the chl genes. The lack of acceleration of the
      dN of the chlB gene might be accounted for by various unknown functions of its
      gene product.

PMID- 16428258
TI  - Health-exposure modeling and the ecological fallacy.
AB  - Recently, there has been an increased interest in modeling the association
      between aggregate disease counts and environmental exposures measured, for
      example via air pollution monitors, at point locations. This paper has two aims:
      first, we develop a model for such data in order to avoid ecological bias;
      second, we illustrate that modeling the exposure surface and estimating exposures
      may lead to bias in estimation of health effects. Design issues are also briefly
      considered, in particular the loss of information in moving from individual to
      ecological data, and the at-risk populations to consider in relation to the
      pollution monitor locations. The approach is investigated initially through
      simulations, and is then applied to a study of the association between mortality
      in those over 65 in the year 2000 and the previous year's SO2, in London. We
      conclude that the use of the proposed model can provide valid inference, but the
      use of estimated exposures should be carried out with great caution.

PMID- 16428259
TI  - The optimal ratio of cases to controls for estimating the classification accuracy
      of a biomarker.
AB  - The case-control design is frequently used to study the discriminatory accuracy
      of a screening or diagnostic biomarker. Yet, the appropriate ratio in which to
      sample cases and controls has never been determined. It is common for researchers
      to sample equal numbers of cases and controls, a strategy that can be optimal for
      studies of association. However, considerations are quite different when the
      biomarker is to be used for classification. In this paper, we provide an
      expression for the optimal case-control ratio, when the accuracy of the biomarker
      is quantified by the receiver operating characteristic (ROC) curve. We show how
      it can be integrated with choosing the overall sample size to yield an efficient
      study design with specified power and type-I error. We also derive the optimal
      case-control ratios for estimating the area under the ROC curve and the area
      under part of the ROC curve. Our methods are applied to a study of a new marker
      for adenocarcinoma in patients with Barrett's esophagus.

PMID- 16428260
TI  - Estimation in regression models for longitudinal binary data with outcome
      dependent follow-up.
AB  - In many observational studies, individuals are measured repeatedly over time,
      although not necessarily at a set of pre-specified occasions. Instead,
      individuals may be measured at irregular intervals, with those having a history
      of poorer health outcomes being measured with somewhat greater frequency and
      regularity. In this paper, we consider likelihood-based estimation of the
      regression parameters in marginal models for longitudinal binary data when the
      follow-up times are not fixed by design, but can depend on previous outcomes. In
      particular, we consider assumptions regarding the follow-up time process that
      result in the likelihood function separating into two components: one for the
      follow-up time process, the other for the outcome measurement process. The
      practical implication of this separation is that the follow-up time process can
      be ignored when making likelihood-based inferences about the marginal regression
      model parameters. That is, maximum likelihood (ML) estimation of the regression
      parameters relating the probability of success at a given time to covariates does
      not require that a model for the distribution of follow-up times be specified.
      However, to obtain consistent parameter estimates, the multinomial distribution
      for the vector of repeated binary outcomes must be correctly specified. In
      general, ML estimation requires specification of all higher-order moments and the
      likelihood for a marginal model can be intractable except in cases where the
      number of repeated measurements is relatively small. To circumvent these
      difficulties, we propose a pseudolikelihood for estimation of the marginal model
      parameters. The pseudolikelihood uses a linear approximation for the conditional
      distribution of the response at any occasion, given the history of previous
      responses. The appeal of this approximation is that the conditional distributions
      are functions of the first two moments of the binary responses only. When the
      follow-up times depend only on the previous outcome, the pseudolikelihood
      requires correct specification of the conditional distribution of the current
      outcome given the outcome at the previous occasion only. Results from a
      simulation study and a study of asymptotic bias are presented. Finally, we
      illustrate the main results using data from a longitudinal observational study
      that explored the cardiotoxic effects of doxorubicin chemotherapy for the
      treatment of acute lymphoblastic leukemia in children.

PMID- 16428261
TI  - Risks for heart disease and lung cancer from passive smoking by workers in the
      catering industry.
AB  - Workers in the catering industry are at greater risk of exposure to secondhand
      smoke (SHS) when smoke-free workplace policies are not in force. We determined
      the exposure of catering workers to SHS in Hong Kong and their risk of death from
      heart disease and lung cancer. Nonsmoking catering workers were provided with
      screening at their workplaces and at a central clinic. Participants reported
      workplace, home, and leisure time exposure to SHS. Urinary cotinine was estimated
      by enzyme immunoassay. Catering facilities were classified into three types:
      nonsmoking, partially restricted smoking (with nonsmoking areas), and
      unrestricted smoking. Mean urinary cotinine levels ranged from 3.3 ng/ml in a
      control group of 16 university staff through 6.4 ng/ml (nonsmoking), 6.1 ng/ml
      (partially restricted), and 15.9 ng/ml (unrestricted smoking) in 104 workers who
      had no exposures outside of work. Workers in nonsmoking facilities had exposures
      to other smoking staff. We modeled workers' mortality risks using average
      cotinine levels, estimates of workplace respirable particulates, risk data for
      cancer and heart disease from cohort studies, and national (US) and regional
      (Hong Kong) mortality for heart disease and lung cancer. We estimated that deaths
      in the Hong Kong catering workforce of 200,000 occur at the rate of 150 per year
      for a 40-year working-lifetime exposure to SHS. When compared with the current
      outdoor air quality standards for particulates in Hong Kong, 30% of workers
      exceeded the 24-h and 98% exceeded the annual air quality objectives due to
      workplace SHS exposures.

PMID- 16428262
TI  - Helicobacter pylori test & treat strategy for dyspepsia: a qualitative study
      exploring the barriers and how to overcome them.
AB  - BACKGROUND: The National Institute of Clinical Excellence (NICE) has issued
      guidance that recommends that all dyspeptic patients without alarm symptoms,
      irrespective of age, that relapse after one month's proton pump inhibitor, should
      be offered test and treat for Helicobacter pylori. OBJECTIVE: To explore the
      views of primary care about introducing the helicobacter test and treat NICE
      dyspepsia guidance. METHODS: In 15 urban and rural general practices in Central
      England, primary health care staff involved in the management of dyspepsia took
      part in qualitative focus groups to discuss the draft NICE guidance and how it
      might be implemented. RESULTS: Practices expressed concern that test and treat
      may not be cost-effective in younger patients and that they may miss malignancy,
      in older patients and in patients who relapse after triple treatment, without a
      further helicobacter test or endoscopy. The greatest practical barriers to test
      and treat were the considerable impact on nurses' and doctors' time to explain,
      undertake tests and report results to patients, and practice budgets from urea
      breath test and triple treatment costs. Staff preferred stool tests to breath
      tests, as they impacted less on practice budget and time. GPs did not favour
      prescribing the three components of the triple treatment separately. CONCLUSIONS:
      GPs will need reassurance that test and treat will not lead to missed
      malignancies. The financial costs and staffing implications of NICE dyspepsia
      guidance will need to be discussed locally by Primary Care Trusts, microbiology
      laboratories, gastroenterologists and pharmacy advisors and implemented with
      local guidance, increased communication and education.

PMID- 16428263
TI  - Genetic test bed for feature selection.
AB  - MOTIVATION: Given a large set of potential features, such as the set of all gene
      expression values from a microarray, it is necessary to find a small subset with
      which to classify. The task of finding an optimal feature set of a given size is
      inherently combinatoric because to assure optimality all feature sets of a given
      size must be checked. Thus, numerous suboptimal feature-selection algorithms have
      been proposed. There are strong impediments to evaluate feature-selection
      algorithms using real data when data are limited, a common situation in genetic
      classification. The difficulty is compound. First, there are no class-conditional
      distributions from which to draw data points, only a single small labeled sample.
      Second, there are no test data with which to estimate the feature-set errors, and
      one must depend on a training-data-based error estimator. Finally, there is no
      optimal feature set with which to compare the feature sets found by the
      algorithms. RESULTS: This paper describes a genetic test bed for the evaluation
      of feature-selection algorithms. It begins with a large biological feature-label
      dataset that is used as an empirical distribution and, using massively parallel
      computation, finds the top feature sets of various sizes based on a given sample
      size and classification rule. The user can draw random samples from the data,
      apply a proposed algorithm, and evaluate the proficiency of the proposed
      algorithm via three different measures (code provided). A key feature of the test
      bed is that, once a dataset is input, a single command creates the entire test
      bed relative to the dataset. The particular dataset used for the first version of
      the test bed comes from a microarray-based classification study that analyzes a
      large number of microarrays, prepared with RNA from breast tumor samples from
      each of 295 patients. AVAILABILITY: The software and supplementary material are
      available at http://public.tgen.org/tgen-cb/support/testbed/ CONTACT:
      edward@ece.tamu.edu.

PMID- 16428264
TI  - Identification of a novel putative mitogen-activated kinase cascade on human
      chromosome 21 by computational approaches.
AB  - Down syndrome (DS) is the most frequent form of mental retardation and is caused
      by chromosome 21 (HSA21) trisomy. Despite the number of known genes involved in
      DS and its high therapeutic interest, biological mechanisms leading to the DS
      phenotype are not fully clear. We present a functional hypothesis based on fold
      recognition and hidden Markov model techniques for four HSA21 genes located in
      the DS Candidate Region (DSCR). More specifically, we propose that they are
      members of a novel mitogen-activated protein kinase pathway with DYRK1A, SNF1LK
      and RIPK4 gene products being elements of the kinase cascade and the DSCR3 acting
      as structural scaffold for their interaction. This hypothesis finds support in
      various biochemical studies concerning the biological behavior and features of
      the involved HSA21 proteins. Our analysis calls for specifically designed
      experiments to validate our prediction and establish its relevance in terms of
      therapeutic approaches to the disease. CONTACT: anna.tramontano@uniroma1.it
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 16428265
TI  - MultiLoc: prediction of protein subcellular localization using N-terminal
      targeting sequences, sequence motifs and amino acid composition.
AB  - MOTIVATION: Functional annotation of unknown proteins is a major goal in
      proteomics. A key annotation is the prediction of a protein's subcellular
      localization. Numerous prediction techniques have been developed, typically
      focusing on a single underlying biological aspect or predicting a subset of all
      possible localizations. An important step is taken towards emulating the protein
      sorting process by capturing and bringing together biologically relevant
      information, and addressing the clear need to improve prediction accuracy and
      localization coverage. RESULTS: Here we present a novel SVM-based approach for
      predicting subcellular localization, which integrates N-terminal targeting
      sequences, amino acid composition and protein sequence motifs. We show how this
      approach improves the prediction based on N-terminal targeting sequences, by
      comparing our method TargetLoc against existing methods. Furthermore, MultiLoc
      performs considerably better than comparable methods predicting all major
      eukaryotic subcellular localizations, and shows better or comparable results to
      methods that are specialized on fewer localizations or for one organism.
      AVAILABILITY: http://www-bs.informatik.uni-tuebingen.de/Services/MultiLoc/

PMID- 16428267
TI  - Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the
      mouse.
AB  - Endogenous hydrogen sulfide (H(2)S) is naturally synthesized in various types of
      mammalian cells from l-cysteine in a reaction catalyzed by two enzymes,
      cystathionine-gamma-lyase (CSE) and/or cystathionine-beta-synthase. The latest
      studies have implied that H(2)S functions as a vasodilator and neurotransmitter.
      However, so far there is little information about the role played by H(2)S in
      systemic inflammation such as sepsis. Thus the aim of this study was to
      investigate the potential role of endogenous H(2)S in cecal ligation and puncture
      (CLP)-induced sepsis. Male Swiss mice were subjected to CLP-induced sepsis and
      treated with saline (ip), dl-propargylglycine (PAG, 50 mg/kg ip), a CSE
      inhibitor, or sodium hydrosulfide (NaHS; 10 mg/kg ip). PAG was administered
      either 1 h before or 1 h after the induction of sepsis, whereas NaHS was given at
      the same time of CLP. CLP-induced sepsis significantly increased the plasma H(2)S
      level and the liver H(2)S synthesis 8 h after CLP compared with sham operation.
      Induction of sepsis also resulted in a significant upregulation of CSE mRNA in
      liver. On the other hand, prophylactic as well as therapeutic administration of
      PAG significantly reduced sepsis-associated systemic inflammation, as evidenced
      by myeloperoxidase activity and histological changes in lung and liver, and
      attenuated the mortality of CLP-induced sepsis. Injection of NaHS significantly
      aggravated sepsis-associated systemic inflammation. Therefore, the effect of
      inhibition of H(2)S formation and administration of NaHS suggests that H(2)S
      plays a proinflammatory role in regulating the severity of sepsis and associated
      organ injury.

PMID- 16428266
TI  - Eradication of Helicobacter pylori infection reverses E-cadherin promoter
      hypermethylation.
AB  - BACKGROUND: E-cadherin methylation is important in gastric carcinogenesis.
      Reversing hypermethylation may halt the carcinogenic process. We have previously
      reported that Helicobacter pylori infection is associated with E-cadherin
      methylation in chronic gastritis patients. AIM: To examine if eradication of H
      pylori could reverse E-cadherin methylation. METHODS: Patients with dyspepsia and
      positive for H pylori infection, with a mucosal biopsy showing chronic active
      gastritis, were randomised to receive H pylori eradication therapy (group 1, n =
      41) or no treatment (group 2, n = 40), and were followed up prospectively.
      Gastric mucosae were taken for methylation assay at week 0 (before treatment) and
      week 6 (after treatment). Archived specimens of intestinal metaplasia with H
      pylori infection (n = 22) and without (n = 19) were retrieved for methylation
      analysis. Methylation was assessed using methylation specific polymerase chain
      reaction and sequencing. RESULTS: Methylation at E-cadherin was detected in 46%
      (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p
      = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H
      pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients,
      intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation
      was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6,
      respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent
      chronic active gastritis in all cases. Methylation frequency did not differ in H
      pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p =
      0.5). CONCLUSION: H pylori eradication therapy could reverse methylation in
      patients with chronic gastritis. This demonstrates an environmental effect on
      methylation.

PMID- 16428268
TI  - Manganese and iron transport across pulmonary epithelium.
AB  - Pathways mediating pulmonary metal uptake remain unknown. Because absorption of
      iron and manganese could involve similar mechanisms, transferrin (Tf) and
      transferrin receptor (TfR) expression in rat lungs was examined. Tf mRNA was
      detected in bronchial epithelium, type II alveolar cells, macrophages, and
      bronchus-associated lymphoid tissue (BALT). Tf protein levels in lung and
      bronchoalveolar lavage fluid did not change in iron deficiency despite increased
      plasma levels, suggesting that lung Tf concentrations are regulated by local
      synthesis in a manner independent of body iron status. Iron oxide exposure
      upregulated Tf mRNA in bronchial and alveolar epithelium, macrophages, and BALT,
      but protein was not significantly increased. In contrast, TfR mRNA and protein
      were both upregulated by iron deficiency. To examine potential interactions with
      lung Tf, rats were intratracheally instilled with (54)Mn or (59)Fe. Unlike
      (59)Fe, interactions between (54)Mn and Tf in lung fluid were not detected.
      Absorption of intratracheally instilled (54)Mn from the lungs to the blood was
      unimpaired in Belgrade rats homozygous for the functionally defective G185R
      allele of divalent metal transporter-1, indicating that this transporter is also
      not involved in pulmonary manganese absorption. Pharmacological studies of (54)Mn
      uptake by A549 cells suggest that metal uptake by type II alveolar epithelial
      cells is associated with activities of both L-type Ca(2+) channels and TRPM7, a
      member of the transient receptor potential melastatin subfamily. These results
      demonstrate that iron and manganese are absorbed by the pulmonary epithelium
      through different pathways and reveal the potential role for nonselective calcium
      channels in lung metal clearance.

PMID- 16428269
TI  - Intracellular Cl- fluxes play a novel role in Ca2+ handling in airway smooth
      muscle.
AB  - Intracellular Ca(2+) is actively sequestered into the sarcoplasmic reticulum
      (SR), whereas the release of Ca(2+) from the SR can be triggered by activation of
      the inositol 1,4,5-trisphosphate and ryanodine receptors. Uptake and release of
      Ca(2+) across the SR membrane are electrogenic processes; accumulation of
      positive or negative charge across the SR membrane could electrostatically hinder
      the movement of Ca(2+) into or out of the SR, respectively. We hypothesized that
      the movement of intracellular Cl(-) (Cl(i)(-)) across the SR membrane neutralizes
      the accumulation of charge that accompanies uptake and release of Ca(2+). Thus
      inhibition of SR Cl(-) fluxes will reduce Ca(2+) sequestration and agonist
      induced release. The Cl(-) channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic
      acid (NPPB; 10(-4) M), previously shown to inhibit SR Cl(-) channels,
      significantly reduced the magnitude of successive acetylcholine-induced
      contractions of airway smooth muscle (ASM), suggesting a "run down" of
      sequestered Ca(2+) within the SR. Niflumic acid (10(-4) M), a structurally
      different Cl(-) channel blocker, had no such effect. Furthermore, NPPB
      significantly reduced caffeine-induced contraction and increases in intracellular
      Ca(2+) concentration ([Ca(2+)](i)). Depletion of Cl(i)(-), accomplished by
      bathing ASM strips in Cl(-)-free buffer, significantly reduced the magnitude of
      successive acetylcholine-induced contractions. In addition, Cl(-) depletion
      significantly reduced caffeine-induced increases in [Ca(2+)](i). Together these
      data suggest a novel role for Cl(i)(-) fluxes in Ca(2+) handling in smooth
      muscle. Because the release of sequestered Ca(2+) is the predominate source of
      Ca(2+) for contraction of ASM, targeting Cl(i)(-) fluxes may prove useful in the
      control of ASM hyperresponsiveness associated with asthma.

PMID- 16428270
TI  - Rac1 and RhoA as regulators of endothelial phenotype and barrier function in
      hypoxia-induced neonatal pulmonary hypertension.
AB  - Hypoxia is a common cause of persistent pulmonary hypertension in the newborn
      (PPHN), a condition associated with endothelial dysfunction and abnormal
      pulmonary vascular remodeling. The GTPase RhoA has been implicated in the
      pathogenesis of PPHN, but its contribution to endothelial remodeling and function
      is not known. We studied pulmonary artery endothelial cells (PAECs) taken from
      piglets with chronic hypoxia-induced pulmonary hypertension and from healthy
      animals and analyzed the roles of Rho GTPases in the regulation of the
      endothelial phenotype and function under basal normoxic conditions, acute
      hypoxia, and reoxygenation. The activities of RhoA, Rac1, and Cdc42 were
      correlated with changes in the endothelial cytoskeleton, adherens junctions,
      permeability, ROS production, VEGF levels, and activities of transcription
      factors hypoxia-inducible factor (HIF)-1alpha and NF-kappaB. Adenoviral gene
      transfer was used to express dominant-negative GTPases, kinase-dead p21-activated
      kinase (PAK)-1, and constitutively activated Rac1 in cells. PAECs from pulmonary
      hypertensive piglets had a stable abnormal phenotype with a sustained reduction
      in Rac1 activity and an increase in RhoA activity, which correlated with an
      increase in actin stress fiber formation, increased permeability, and a decrease
      in VEGF and ROS production. Cells from pulmonary hypertensive animals were still
      able to respond to acute hypoxia. They also showed high activities of HIF-1alpha
      and NF-kappaB, likely to result from changes in the activities of Rho GTPases.
      Activation of Rac1 and its effector PAK-1 as well as inhibition of RhoA restored
      the abnormal phenotype and permeability of hypertensive PAECs to normal.

PMID- 16428271
TI  - TNF-alpha and IFN-gamma inversely modulate expression of the IL-17E receptor in
      airway smooth muscle cells.
AB  - The interleukin-17B receptor (IL-17BR) is expressed in a variety of tissues and
      is upregulated under inflammatory conditions. This receptor binds both its
      cognate ligand IL-17B and IL-17E/IL-25, a novel cytokine known to promote Th2
      responses. The present study shows that airway smooth muscle cells express IL
      17BR in vitro and that its expression is upregulated by TNF-alpha and
      downregulated by IFN-gamma. Our data indicate that TNF-alpha upregulates IL-17BR
      mainly through nuclear factor-kappaB as assessed with the IkappaB kinase 2
      inhibitor AS-602868. In addition, both IFN-gamma and dexamethasone are able to
      antagonize a TNF-alpha-induced IL-17BR increase in mRNA expression. The mitogen
      activated protein kinase kinase inhibitor U0126 totally reversed the inhibition
      observed with IFN-gamma, suggesting the involvement of the extracellular signal
      regulated kinase pathway in this effect. In addition, on stimulation with IL-17E,
      airway smooth muscle cells increase their expression of ECM components, namely
      procollagen-alphaI and lumican mRNA. Furthermore, immunohistochemical analysis of
      biopsies from asthmatic subjects reveals that this receptor is abundant in smooth
      muscle layers. This is the first report showing IL-17BR receptor in structural
      cells of the airways. Our results suggest a potential proremodeling effect of IL
      17E on airway smooth muscle cells through the induction of ECM and that its
      receptor is upregulated by proinflammatory conditions.

PMID- 16428272
TI  - Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell
      turnover.
AB  - Tight regulation of VEGF-A production and signaling is important for the
      maintenance of lung development and homeostasis. VEGF null mice have provided
      little insight into the role of VEGF during the later stages of lung
      morphogenesis. Therefore, we examined the in vitro effects of autocrine and
      paracrine VEGF-A production and the inhibition of VEGF-A signaling on a Flk-1
      negative subset of fetal pulmonary mesenchymal cells (pMC). We hypothesized that
      VEGF-A receptor signaling regulates turnover of fetal lung mesenchyme in a cell
      cycle-dependent manner. VEGF receptor blockade with SU-5416 caused cell spreading
      and decreased proliferation and bcl-2 localization. Nuclear expression of the
      cell cycle inhibitory protein, p21, was increased with SU-5416 treatment, and p27
      was absent. Autocrine VEGF production by pMC resulted in proliferation and
      p21/p27-dependent contact inhibition. In contrast, exogenous VEGF-A increased
      cell progression through the cell cycle. Selective activation of Flt by placental
      growth factor demonstrated the importance of this receptor/kinase in the VEGF-A
      responsiveness of pMC. The expression and localization of the survival factor bcl
      2 was dependent on VEGF. These results provide evidence that VEGF-A plays a
      critical role in the regulation of fetal pulmonary mesenchymal proliferation,
      survival, and the subsequent development of normal lung architecture through bcl
      2 and p21/p27-dependent cell cycle control.

PMID- 16428273
TI  - Hydrogen-bonding dynamics between adjacent blades in G-protein beta-subunit
      regulates GIRK channel activation.
AB  - Functionally critical domains in the betagamma-subunits of the G-protein
      (Gbetagamma) do not undergo large structural rearrangements upon binding to other
      proteins. Here we show that a region containing Ser(67) and Asp(323) of
      Gbetagamma is a critical determinant of G-protein-gated inwardly rectifying K(+)
      (GIRK) channel activation and undergoes only small structural changes upon
      mutation of these residues. Using an interactive experimental and computational
      approach, we show that mutants that form a hydrogen-bond between positions 67 and
      323 do not activate a GIRK channel. We also show that in the absence of hydrogen
      bonding between these positions, other factors, such as the displacement of the
      crucial Ggamma residues Pro(60) and Phe(61), can impair Gbetagamma-mediated GIRK
      channel activation. Our results imply that the dynamic nature of the hydrogen
      bonding pattern in the wild-type serves an important functional role that
      regulates GIRK channel activation by Gbetagamma and that subtle changes in the
      flexibility of critical domains could have substantial functional consequences.
      Our results further strengthen the notion that the dynamic regulation of multiple
      interactions between Gbetagamma and effectors provides for a complex regulatory
      process in cellular functions.

PMID- 16428274
TI  - Carotenoid-bacteriochlorophyll energy transfer in LH2 complexes studied with 10
      fs time resolution.
AB  - In this report, we present a study of carotenoid-bacteriochlorophyll energy
      transfer processes in two peripheral light-harvesting complexes (known as LH2)
      from purple bacteria. We use transient absorption spectroscopy with approximately
      10 fs temporal resolution, which is necessary to observe the very fast energy
      relaxation processes. By comparing excited-state dynamics of the carotenoids in
      organic solvents and inside the LH2 complexes, it has been possible to directly
      evaluate their energy transfer efficiency to the bacteriochlorophylls. In the
      case of okenone in the LH2 complex from Chromatium purpuratum, we obtained an
      energy transfer efficiency of etaET2=63+/-2.5% from the optically active excited
      state (S2) and etaET1=61+/-2% from the optically dark state (S1); for rhodopin
      glucoside contained in the LH2 complex from Rhodopseudomonas acidophila these
      values become etaET2=49.5+/-3.5% and etaET1=5.1+/-1%. The measurements also
      enabled us to observe vibrational energy relaxation in the carotenoids' S1 state
      and real-time collective vibrational coherence initiated by the ultrashort pump
      pulses. Our results are important for understanding the dynamics of early events
      of photosynthesis and relating it to the structural arrangement of the
      chromophores.

PMID- 16428275
TI  - Hydration dependence of conformational dielectric relaxation of lysozyme.
AB  - Dielectric response of hen egg white lysozyme is measured in the far infrared (5
      65 cm-1, 0.15-1.95 THz, 0.6-8.1 meV) as a function of hydration. The frequency
      range is associated with collective vibrational modes of protein tertiary
      structure. The observed frequency dependence of the absorbance is broad and glass
      like. For the entire frequency range, there is a slight increase in both the
      absorbance and index of refraction with increasing hydration for <0.27 h (mass of
      H2O per unit mass protein). At 0.27 h, the absorbance and index begin to increase
      more rapidly. This transition corresponds to the point where the first hydration
      shell is filled. The abrupt increase in dielectric response cannot be fully
      accounted for by the additional contribution to the dielectric response due to
      bulk water, suggesting that the protein has not yet achieved its fully hydrated
      state. The broad, glass-like response suggests that at low hydrations, the low
      frequency conformational hen egg white lysozyme dynamics can be described by a
      dielectric relaxation model where the protein relaxes to different local minima
      in the conformational energy landscape. However, the low frequency complex
      permittivity does not allow for a pure relaxational mechanism. The data can best
      be modeled with a single low frequency resonance (nu approximately 120 GHz=4 cm
      1) and a single Debye relaxation process (tau approximately .03-.04 ps).
      Terahertz dielectric response is currently being considered as a possible
      biosensing technique and the results demonstrate the required hydration control
      necessary for reliable biosensor applications.

PMID- 16428276
TI  - Salt enhances calmodulin-target interaction.
AB  - Calmodulin (CaM) operates as a Ca(2+) sensor and is known to interact with and
      regulate hundreds of proteins involved in a great many aspects of cellular
      function. It is of considerable interest to understand the balance of forces in
      complex formation of CaM with its target proteins. Here we have studied the
      importance of electrostatic interactions in the complex between CaM and a peptide
      derived from smooth-muscle myosin light-chain kinase by experimental methods and
      Monte Carlo simulations of electrostatic interactions. We show by Monte Carlo
      simulations that, in agreement with experimental data, the binding affinity
      between CaM and highly charged peptides is surprisingly insensitive to changes in
      the net charge of both the protein and peptide. We observe an increase in the
      binding affinity between oppositely charged partners with increasing salt
      concentration from zero to 100 mM, showing that formation of globular CaM-kinase
      type complexes is facilitated at physiological ionic strength. We conclude that
      ionic interactions in complex formation are optimized at pH and saline similar to
      the cell environment, which probably overrules the electrostatic repulsion
      between the negatively charged Ca(2+)-binding domains of CaM. We propose a
      conceivable rationalization of CaM electrostatics associated with interdomain
      repulsion.

PMID- 16428277
TI  - Mechanical properties and consequences of stereocilia and extracellular links in
      vestibular hair bundles.
AB  - Although knowledge of the fine structure of vestibular hair bundles is
      increasing, the mechanical properties and functional significance of those
      structures remain unclear. In 2004, Bashtanov and colleagues reported the
      contribution of different extracellular links to bundle stiffness. We simulated
      Bashtanov's experimental protocol using a three-dimensional finite element bundle
      model with geometry measured from a typical striolar hair cell. Unlike any
      previous models, we separately consider two types of horizontal links: shaft
      links and upper lateral links. Our most important results are as follows. First,
      we identified the material properties required to match Bashtanov's experiment:
      stereocilia Young's modulus of 0.74 GPa, tip link assembly (gating spring)
      stiffness of 5,300 pN/microm, and the combined stiffness of shaft links binding
      two adjacent stereocilia of 750 approximately 2,250 pN/microm. Second, we
      conclude that upper lateral links are likely to have nonlinear mechanical
      properties: they have minimal stiffness during small bundle deformations but
      stiffen as the bundle deflects further. Third, we estimated the stiffness of the
      gating spring based on our realistic three-dimensional bundle model rather than a
      conventional model relying on the parallel arrangement assumption. Our predicted
      stiffness of the gating spring was greater than the previous estimation.

PMID- 16428279
TI  - The open nucleotide pocket of the profilin/actin x-ray structure is unstable and
      closes in the absence of profilin.
AB  - The open nucleotide pocket conformation of actin in the profilin:actinCaATP x-ray
      structure has been hypothesized to be a crucial intermediate for nucleotide
      exchange in the actin depolymerization/polymerization cycle. The requirement for
      ancillary modification of actin for crystallization leads to ambiguities in this
      interpretation, however. We have used molecular dynamics simulations to model the
      thermodynamic properties of the actin x-ray structure, outside the crystal
      lattice, in an aqueous environment with profilin removed. Our simulations show
      that the open-nucleotide-pocket, profilin-free structure is actually unstable,
      and closes. The coordination of actin to the nucleotide in the molecular-dynamics
      derived closed structure is virtually identical to that in the closed
      profilin:actinSrATP x-ray structure. Thus, there is currently no
      thermodynamically stable structure representing the open-nucleotide-pocket state
      of actin.

PMID- 16428278
TI  - Molecular dynamics simulations of model trans-membrane peptides in lipid
      bilayers: a systematic investigation of hydrophobic mismatch.
AB  - Hydrophobic mismatch, which is the difference between the hydrophobic length of
      trans-membrane segments of a protein and the hydrophobic width of the surrounding
      lipid bilayer, is known to play a role in membrane protein function. We have
      performed molecular dynamics simulations of trans-membrane KALP peptides
      (sequence: GKK(LA)nLKKA) in phospholipid bilayers to investigate hydrophobic
      mismatch alleviation mechanisms. By varying systematically the length of the
      peptide (KALP15, KALP19, KALP23, KALP27, and KALP31) and the lipid hydrophobic
      length (DLPC, DMPC, and DPPC), a wide range of mismatch conditions were studied.
      Simulations of durations of 50-200 ns show that under positive mismatch, the
      system alleviates the mismatch predominantly by tilting the peptide and to a
      smaller extent by increased lipid ordering in the immediate vicinity of the
      peptide. Under negative mismatch, alleviation takes place by a combination of
      local bilayer bending and the snorkeling of the lysine residues of the peptide.
      Simulations performed at a higher peptide/lipid molar ratio (1:25) reveal slower
      dynamics of both the peptide and lipid relative to those at a lower peptide/lipid
      ratio (1:128). The lysine residues have favorable interactions with specific
      oxygen atoms of the phospholipid headgroups, indicating the preferred
      localization of these residues at the lipid/water interface.

PMID- 16428280
TI  - Evaluation of the information content in infrared spectra for protein secondary
      structure determination.
AB  - Fourier-transform infrared spectroscopy is a method of choice for the
      experimental determination of protein secondary structure. Numerous approaches
      have been developed during the past 15 years. A critical parameter that has not
      been taken into account systematically is the selection of the wavenumbers used
      for building the mathematical models used for structure prediction. The high
      quality of the current Fourier-transform infrared spectrometers makes the
      absorbance at every single wavenumber a valid and almost noiseless type of
      information. We address here the question of the amount of independent
      information present in the infrared spectra of proteins for the prediction of the
      different secondary structure contents. It appears that, at most, the absorbance
      at three distinct frequencies of the spectra contain all the nonredundant
      information that can be related to one secondary structure content. The ascending
      stepwise method proposed here identifies the relevance of each wavenumber of the
      infrared spectrum for the prediction of a given secondary structure and yields a
      particularly simple method for computing the secondary structure content. Using
      the 50-protein database built beforehand to contain as little fold redundancy as
      possible, the standard error of prediction in cross-validation is 5.5% for the
      alpha-helix, 6.6% for the beta-sheet, and 3.4% for the beta-turn.

PMID- 16428281
TI  - Continuous photobleaching in vesicles and living cells: a measure of diffusion
      and compartmentation.
AB  - We present a comprehensive and analytical treatment of continuous photobleaching
      in a compartment, under single photon excitation. In the very short time regime
      (t<0.1 ms), the diffusion does not play any role. After a transition (or short
      time regime), one enters in the long time regime (t>0.1-5 s), for which the
      diffusion and the photobleaching balance each other. In this long time regime,
      the diffusion is either fast (i.e., the photobleaching probability of a molecule
      diffusing through the laser beam is low) so that the photobleaching rate is
      independent of the diffusion constant and dependent only of the laser power, or
      the diffusion is slow (i.e., the photobleaching probability is high) and the
      photobleaching rate is mainly dependent on the diffusion constant. We illustrate
      our theory by using giant unilamellar vesicles ranging from approximately 10 to
      100 microm in diameter, loaded with molecules of various diffusion constants
      (from 20 to 300 microm2/s) and various photobleaching cross sections, illuminated
      under laser powers between 3 and 100 microW. We also demonstrated that
      information about compartmentation can be obtained by this method in living cells
      expressing enhanced green fluorescent proteins or that were loaded with small
      FITC-dextrans. Our quantitative approach shows that molecules freely diffusing in
      a cellular compartment do experience a continuous photobleaching. We provide a
      generic theoretical framework that should be taken into account when studying,
      under confocal microscopy, molecular interactions, permeability, etc.

PMID- 16428282
TI  - Nearly neutral secretory vesicles in Drosophila nerve terminals.
AB  - The acidity of mammalian secretory vesicles drives concentration and processing
      of their contents. Here, pH-sensitive green fluorescent protein (GFP) variants
      show that the > or =30-fold (H+) difference between secretory vesicles (pH < or =
      5.7) and the cytoplasm (pH = 7.2) in mammalian cells is not present in
      peptidergic and small synaptic vesicles of the Drosophila neuromuscular junction.
      First, we find that fluorescence from Topaz-tagged atrial natriuretic factor, a
      peptidergic vesicle pH indicator, is only modestly affected by collapsing the H+
      gradient in type III synaptic boutons. Quantitation shows that peptidergic
      vesicles are nearly neutral (pH = 6.74 +/- 0.05), even when temperature is
      elevated. Furthermore, small synaptic vesicles in glutamatergic synaptic boutons,
      studied with synaptophluorin, are as alkaline as peptidergic vesicles. Finally,
      yellow fluorescent protein measurements show that cytoplasmic pH is only slightly
      different than in mammals (pH = 7.4). Thus, the marked acidity of mammalian
      secretory vesicles is not conserved in evolution, and a modest vesicular H+
      gradient is sufficient for supporting neurotransmission.

PMID- 16428283
TI  - Binary and ternary aggregation within tethered protein constructs.
AB  - The free energy per monomer of a protein aggregate varies with the number of
      participating monomers n. The change of this free energy with aggregate size,
      DeltaDeltaG(n), is difficult to determine by sedimentation or concentration
      studies. We introduce a kinetic approach to quantitate the free energy of
      aggregates in the presence of tethers. By linking the protein U1A into dimers and
      trimers, a high effective concentration of the monomers is achieved, together
      with exact size control of the aggregates. We found that the free energy of the
      aggregate relative to the native monomer reached a maximum for n = 2, and
      decreased by DeltaDeltaG(2) = -3.1 kT between dimer and trimer.

PMID- 16428284
TI  - Investigating the local flexibility of functional residues in hemoproteins.
AB  - It is now widely accepted that protein function depends not only on structure,
      but also on flexibility. However, the way mechanical properties contribute to
      catalytic mechanisms remains unclear. Here, we propose a method for investigating
      local flexibility within protein structures that combines a reduced protein
      representation with Brownian dynamics simulations. An analysis of residue
      fluctuations during the dynamics simulation yields a rigidity profile for the
      protein made up of force constants describing the ease of displacing each residue
      with respect to the rest of the structure. This approach has been applied to the
      analysis of a set of hemoproteins, one of the functionally most diverse protein
      families. Six proteins containing one or two heme groups have been studied,
      paying particular attention to the mechanical properties of the active-site
      residues. The calculated rigidity profiles show that active site residues are
      generally associated with high force constants and thus rigidly held in place.
      This observation also holds for diheme proteins if their mechanical properties
      are analyzed domain by domain. We note, however, that residues other than those
      in the active site can also have high force constants, as in the case of residues
      belonging to the folding nucleus of c-type hemoproteins.

PMID- 16428285
TI  - Bifurcation and singularity analysis of a molecular network for the induction of
      long-term memory.
AB  - Withdrawal reflexes of the mollusk Aplysia exhibit sensitization, a simple form
      of long-term memory (LTM). Sensitization is due, in part, to long-term
      facilitation (LTF) of sensorimotor neuron synapses. LTF is induced by the
      modulatory actions of serotonin (5-HT). Pettigrew et al. developed a
      computational model of the nonlinear intracellular signaling and gene network
      that underlies the induction of 5-HT-induced LTF. The model simulated empirical
      observations that repeated applications of 5-HT induce persistent activation of
      protein kinase A (PKA) and that this persistent activation requires a
      suprathreshold exposure of 5-HT. This study extends the analysis of the Pettigrew
      model by applying bifurcation analysis, singularity theory, and numerical
      simulation. Using singularity theory, classification diagrams of parameter space
      were constructed, identifying regions with qualitatively different steady-state
      behaviors. The graphical representation of these regions illustrates the
      robustness of these regions to changes in model parameters. Because persistent
      protein kinase A (PKA) activity correlates with Aplysia LTM, the analysis focuses
      on a positive feedback loop in the model that tends to maintain PKA activity. In
      this loop, PKA phosphorylates a transcription factor (TF-1), thereby increasing
      the expression of an ubiquitin hydrolase (Ap-Uch). Ap-Uch then acts to increase
      PKA activity, closing the loop. This positive feedback loop manifests multiple,
      coexisting steady states, or multiplicity, which provides a mechanism for a
      bistable switch in PKA activity. After the removal of 5-HT, the PKA activity
      either returns to its basal level (reversible switch) or remains at a high level
      (irreversible switch). Such an irreversible switch might be a mechanism that
      contributes to the persistence of LTM. The classification diagrams also identify
      parameters and processes that might be manipulated, perhaps pharmacologically, to
      enhance the induction of memory. Rational drug design, to affect complex
      processes such as memory formation, can benefit from this type of analysis.

PMID- 16428286
TI  - Effects of a short-chain ceramide on bilayer domain formation, thickness, and
      chain mobililty: DMPC and asymmetric ceramide mixtures.
AB  - An important part of natural ceramides contain asymmetric hydrocarbon chains. We
      have used calorimetry, atomic force microscopy, and electron paramagnetic
      resonance to study the effect of ceramide chain asymmetry in mixtures of C8Cer
      with DMPC as a model system of hydrocarbon chain disparity. A phase diagram is
      provided along with information on the thickness of the membrane and the mobility
      of the chains at different temperatures both below and above the phase transition
      temperature of the mixtures. The results indicate a partial interdigitation of
      C8Cer chains in the gel phase, producing a correlation between the organization
      of both hemilayers. Our data suggest that the effects of ceramides on
      biomembranes may be bimodal and similar to those of cholesterol.

PMID- 16428288
TI  - Foamy virus vector integration sites in normal human cells.
AB  - Foamy viruses (FVs) or spumaviruses are retroviruses that have been developed as
      vectors, but their integration patterns have not been described. We have
      performed a large-scale analysis of FV integration sites in unselected human
      fibroblasts (n = 1,008) and human CD34(+) hematopoietic cells (n = 1,821) by
      using a bacterial shuttle vector and a comparable analysis of lentiviral vector
      integration sites in CD34(+) cells (n = 1,331). FV vectors had a distinct
      integration profile relative to other types of retroviruses. They did not
      integrate preferentially within genes, despite a modest preference for
      integration near transcription start sites and a significant preference for CpG
      islands. The genomewide distribution of FV vector proviruses was nonrandom, with
      both clusters and gaps. Transcriptional profiling showed that gene expression had
      little influence on integration site selection. Our findings suggest that FV
      vectors may have desirable integration properties for gene therapy applications.

PMID- 16428287
TI  - Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms.
AB  - WNK kinases are serine-threonine kinases with an atypical placement of the
      catalytic lysine. Intronic deletions with increased expression of a ubiquitous
      long WNK1 transcript cause pseudohypoaldosteronism type 2 (PHA II), characterized
      by hypertension and hyperkalemia. Here, we report that long WNK1 inhibited ROMK1
      by stimulating its endocytosis. Inhibition of ROMK by long WNK1 was synergistic
      with, but not dependent on, WNK4. A smaller transcript of WNK1 lacking the N
      terminal 1-437 amino acids is expressed highly in the kidney. Whether expression
      of the KS-WNK1 (kidney-specific, KS) is altered in PHA II is not known. We found
      that KS-WNK1 did not inhibit ROMK1 but reversed the inhibition of ROMK1 caused by
      long WNK1. Consistent with the lack of inhibition by KS-WNK1, we found that amino
      acids 1-491 of the long WNK1 were sufficient for inhibiting ROMK. Dietary K(+)
      restriction decreases ROMK abundance in the renal cortical-collecting ducts by
      stimulating endocytosis, an adaptative response important for conservation of
      K(+) during K(+) deficiency. We found that K(+) restriction in rats increased
      whole-kidney transcript of long WNK1 while decreasing that of KS-WNK1. Thus, KS
      WNK1 is a physiological antagonist of long WNK1. Hyperkalemia in PHA II patients
      with PHA II mutations may be caused, at least partially, by increased expression
      of long WNK1 with or without decreased expression of KS-WNK1.

PMID- 16428289
TI  - Ancient polymorphism reveals unidirectional breeding system shifts.
AB  - Loss of complex characters is thought to be irreversible (Dollo's law). However,
      hypotheses of irreversible evolution are remarkably difficult to test, especially
      when character transitions are frequent. In such cases, inference of ancestral
      states, in the absence of fossil evidence, is uncertain and represents the single
      greatest constraint for reconstructing the evolutionary history of characters.
      Breeding system character transitions are of particular interest because they
      affect the amount and distribution of genetic variation within species.
      Transitions from obligate outcrossing to partial or predominant self
      fertilization are thought to represent one of the most common trends in flowering
      plants. We use the unique molecular genetic properties (manifested as deep
      persistent polymorphisms) of the locus that enforces outcrossing to demonstrate
      that its loss is irreversible in the plant family Solanaceae. We argue that
      current phylogenetic methods of reconstruction are potentially inadequate in
      cases where ancestral state information is inferred by using only the phylogeny
      and the distribution of character states in extant taxa. This study shows in a
      statistical framework that a particular character transition is irreversible,
      consistent with Dollo's law.

PMID- 16428291
TI  - Oil market power and United States national security.
AB  - It is widely believed that an oil weapon could impose scarcity upon the United
      States. Impending resource exhaustion is thought to exacerbate this threat.
      However, threat seems implausible when we consider strategic deficits of
      prospective weapon users and the improbability of impending resource exhaustion.
      Here, we explore a hypothesis relating oil to national security under a different
      assumption, abundance. We suggest that an oil cartel exerts market power to keep
      abundance at bay, commanding monopoly rents [or wealth transfers (wt)] that
      underwrite security threats. We then compare security threats attributed to the
      oil weapon to those that may arise from market power. We first reexamine whether
      oil is abundant or scarce by reviewing current development data, then we estimate
      a competitive price for oil. From this, we derive wt(2004) collections by Persian
      Gulf states approximately USD $132-178 x 10(9). We find that wt and the behavior
      of states collecting it interact to actuate security threats. Threats
      underwritten by wt are (i) the potential for emergence of a Persian Gulf
      superpower and (ii) terrorism. It is therefore oil market power, not oil per se,
      that actuates threats. We also describe a paradox in the relation of market power
      to the United States' defense doctrine of force projection to preempt a Gulf
      superpower. Because the superpower threat derives from wt, force alone cannot
      preempt it. A further paradox is that because foreign policy is premised on oil
      weapon fear, market power is appeased. Threats thereby grow unimpeded.

PMID- 16428290
TI  - Reconciling the working strokes of a single head of skeletal muscle myosin
      estimated from laser-trap experiments and crystal structures.
AB  - Myosin generates force by a rotation of its lever arm. Crystal structures of
      myosin II indicate an unloaded working stroke of 10-12 nm, a range confirmed by
      recent x-ray interference experiments. However, when an actin filament, held
      between two weakly, optically trapped beads is made to interact with a single
      head of skeletal myosin, the bead displacements have often been reported as
      having a mean value of 5-6 nm, a value that is commonly interpreted as the
      working stroke. In general, the observed displacement is not expected to be equal
      to the working stroke because the kinetics of the stroke is necessarily strain
      dependent: this effect biases the frequency of binding events to different actin
      sites so that displacements smaller than the working stroke are preferentially
      selected. Our analysis is tailored to current trap experiments, in which the time
      resolution is insufficient to detect pre-rigor states. If the preceding
      transitions are in equilibrium, the mean displacement is zero, contrary to
      observations in the presence of ATP. However, under ATP-cycling conditions, we
      find that the mean displacement is deflated to 0.3-0.7 of the true working
      stroke, depending on the equilibrium constant of the stroke and the rate at which
      the first myosin product state can detach from actin. The primary working stroke
      of processive myosin motors as measured by optical trapping is similarly
      uncertain.

PMID- 16428292
TI  - Plant community responses to experimental warming across the tundra biome.
AB  - Recent observations of changes in some tundra ecosystems appear to be responses
      to a warming climate. Several experimental studies have shown that tundra plants
      and ecosystems can respond strongly to environmental change, including warming;
      however, most studies were limited to a single location and were of short
      duration and based on a variety of experimental designs. In addition, comparisons
      among studies are difficult because a variety of techniques have been used to
      achieve experimental warming and different measurements have been used to assess
      responses. We used metaanalysis on plant community measurements from standardized
      warming experiments at 11 locations across the tundra biome involved in the
      International Tundra Experiment. The passive warming treatment increased plant
      level air temperature by 1-3 degrees C, which is in the range of predicted and
      observed warming for tundra regions. Responses were rapid and detected in whole
      plant communities after only two growing seasons. Overall, warming increased
      height and cover of deciduous shrubs and graminoids, decreased cover of mosses
      and lichens, and decreased species diversity and evenness. These results predict
      that warming will cause a decline in biodiversity across a wide variety of
      tundra, at least in the short term. They also provide rigorous experimental
      evidence that recently observed increases in shrub cover in many tundra regions
      are in response to climate warming. These changes have important implications for
      processes and interactions within tundra ecosystems and between tundra and the
      atmosphere.

PMID- 16428293
TI  - A decade of histone acetylation: marking eukaryotic chromosomes with specific
      codes.
AB  - Post-translational modification of histones, a major protein component of
      eukaryotic chromosomes, contributes to the epigenetic regulation of gene
      expression. Distinct patterns of histone modification are observed at specific
      chromosomal regions and affect various reactions on chromosomes (transcription,
      replication, repair, and recombination). Histone modification has long been
      proposed to have a profound effect on eukaryotic gene expression since its
      discovery in 1964. Verification of this idea, however, was difficult until the
      identification of enzymes responsible for histone modifications. Ten years ago
      (1995), histone acetyltransferases (HATs), which acetylate lysine residues in
      histone amino-terminal tail regions, were isolated. HATs are involved in the
      regulation of both promoter-specific transcription and long-range/chromosome-wide
      transcription. Analyses of HATs and other modification enzymes have revealed
      mechanisms of epigenetic regulation that are mediated by post-translational
      modifications of histones. Here we review some major advances in the field, with
      emphasis on the lysine specificity of the acetylation reaction and on the
      regulation of gene expression over broad regions.

PMID- 16428294
TI  - Typical three-domain cry proteins of Bacillus thuringiensis strain A1462 exhibit
      cytocidal activity on limited human cancer cells.
AB  - Bacillus thuringiensis strain A1462 produced two parasporal inclusion proteins
      with a molecular mass of 88 kDa that were converted to 64-kDa toxins when
      activated by proteinase K digestion. Both toxins exhibited strong cytocidal
      activity against two human cancer cell lines, HL60 (myeloid leukemia cells) and
      HepG2 (liver cancer cells), while low or no toxicities were observed against 11
      human and three mammalian cell lines, including four non-cancer cell lines. The
      cytotoxicity of both toxins on susceptible cells was characterized by rapid cell
      swelling. Gene cloning experiments provided two novel genes encoding 88-kDa Cry
      proteins, Cry41Aa and Cry41Ab. The amino acid sequences of the two proteins
      contain five block regions commonly conserved in B. thuringiensis insecticidal
      Cry proteins. This is the first report of the occurrence of typical three-domain
      Cry proteins with cytocidal activity preferential for cancer cells.

PMID- 16428295
TI  - PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid.
AB  - Human mitochondrial DNA takes on a large protein-DNA complex called a nucleoid or
      mitochromosome. Mitochondrial transcription factor A (TFAM) is a major component
      of the complex. During an attempt to search for proteins associated with the TFAM
      containing complex by a proteomic method, we found one protein that has not been
      considered to be mitochondrial: PDIP38. PDIP38 was initially identified as a
      binding protein to nuclear DNA polymerase delta. PDIP38 is almost exclusively
      recovered from the mitochondrial fraction of human HeLa cells. PDIP38 is
      completely cleaved when TritonX-100-solubilized mitochondria are treated with
      proteinase K, but not when mitoplasts devoid of outer membranes are treated,
      indicating that PDIP38 is located in the mitochondrial matrix. TFAM and
      mitochondrial single-stranded DNA binding protein (mtSSB) are co
      immunoprecipitated with PDIP38 by anti-PDIP38 antibodies. On the other hand, only
      the latter is crosslinked to PDIP38 when mitochondria are treated with a
      crosslinker, formaldehyde. In addition to mtSSB, 60 kDa heat shock protein and a
      Lon protease homolog, both of which have single-stranded DNA binding activity,
      are also crosslinked. PDIP38 associates with the nucleoid components and could be
      involved in the metabolism of mitochondrial DNA.

PMID- 16428296
TI  - Structure-activity relationship of polyphenols that inhibit fatty acid synthase.
AB  - Many flavone derivatives inhibit FAS, and their A and B rings play an important
      role, but is the C ring necessary for the inhibition of FAS? Here, using
      nordihydroguaiaretic acid (NDGA), with two phenyl rings connected by a four
      carbon chain, as a representative, the structural basis for the inhibition of
      animal fatty acid synthase (FAS) by polyphenols was investigated. NDGA potently
      inhibits the overall reaction of FAS (IC(50) = 9.3 +/- 0.1 muM). The kinetic
      study indicated that NDGA inhibits FAS competitively with respect to acetyl-CoA,
      noncompetitively with respect to malonyl-CoA, and in a mixed manner with respect
      to NADPH. The inhibitory mechanism is the same as that of FAS flavonoid
      inhibitors. This suggests that the C ring of flavonoids is not essential for
      their FAS inhibitory effect. This conclusion was further confirmed by the results
      obtained for different polyphenols. A structure-activity relationship study
      indicated that a biphenyl core exists in all FAS polyphenol inhibitors. Thus, we
      propose a common model possibly shared by all FAS polyphenol inhibitors. The
      model includes two almost planar aromatic rings with their respective hydroxyl
      groups, and a proper ester linkage between the two rings that possibly causes the
      inhibition of FAS by irreversibly inhibiting the beta-ketoacyl reductase domain.

PMID- 16428297
TI  - Nitration of profilin effects its interaction with poly (L-proline) and actin.
AB  - Profilin from bovine spleen was nitrated with peroxynitrite; immunoblotting and
      spectrophotometric quantitation of nitrotyrosine residues suggested nitration of
      a single tyrosine residue in profilin with a stoichiometry of 0.6 mol of
      nitrotyrosine/mole of profilin. A decrease in the nitrotyrosine immunoreactivity
      of nitroprofilin during digestion with carboxypeptidase Y indicated that
      nitrotyrosine is located at the C-terminus of profilin. Nitroprofilin interaction
      with ligands such as phosphatidylinositol 4,5-bisphosphate, actin and poly (l
      proline) was analyzed by monitoring the tryptophan fluorescence. Scatchard plot
      and binding isotherm data obtained revealed no significant difference in affinity
      of nitroprofilin to phosphatidylinositol 4,5-bisphosphate (K(d) of 4.8 +/- 0.5
      muM for profilin, and K(d) of 5.7 +/- 0.6 muM for nitroprofilin), while poly (l
      proline) binding studies revealed a twenty-fold increase in the affinity of
      profilin to poly (l-proline) upon nitration (K(d) of 21.8 +/- 1.7 muM for
      profilin, and K(d) of 1.1 +/- 0.1 muM for nitroprofilin). Actin polymerization
      studies involving pyrene-labeled actin indicated that profilin nitration inhibits
      the actin sequestering property of profilin. The critical actin monomer
      concentration (C(c)) was 150 and 250 nM in the presence of nitroprofilin and
      profilin, respectively. Thus, nitric oxide and free radicals produced under
      different conditions could alter the functions of profilin through nitration,
      such as its interaction with actin and poly (l-proline).

PMID- 16428298
TI  - Characterization of the protein phosphatase 1-binding motifs of inhibitor-2 and
      DARPP-32 by surface plasmon resonance.
AB  - KLHY is a short amino-acid sequence of inhibitor-2. This sequence is highly
      conserved with the protein phosphatase 1 (PP1)-binding consensus motif, RVXF. The
      role of this segment in binding with PP1 is ambiguous. By using surface plasmon
      resonance we have characterized its binding ability to PP1. Either site-directed
      mutagenesis or deletion of KLHY did not significantly affect the dissociation
      constant between PP1 and inhibitor-2. In comparison with DARPP-32, the deletion
      of KKIQF, a PP1-binding motif of DARPP-32, resulted in a remarkable reduction in
      its affinity with PP1. Our results suggested that, compared with the common RVXF
      motif, the KLHY sequence in intact inhibitor-2 binds weakly to PP1.

PMID- 16428299
TI  - Molecular cloning of the gene encoding Vibrio metalloproteinase vimelysin and
      isolation of a mutant with high stability in organic solvents.
AB  - Vimelysin is a unique metalloproteinase from Vibrio sp. T1800 exhibiting high
      activity at low temperature and high stability in organic solvents such as
      ethanol. A 1,821 bp open reading frame of the vimelysin gene encoded 607 amino
      acid residues consisting of an N-terminal pro-region, a mature enzyme, and a C
      terminal pro-region. The mature enzyme region showed 80%, 57% and 35% sequence
      identity with the mature forms of vibriolysin from V. vulnificus, pseudolysin
      from Pseudomonas aeruginosa, and thermolysin from Bacillus thermoproteolyticus,
      respectively. The catalytic residues and zinc-binding motifs of
      metalloproteinases are well conserved in vimelysin. The vimelysin gene was
      expressed in E. coli JM109 cells and the recombinant enzyme was purified as a 38
      kDa mature form from cell-free extracts. The purified recombinant enzyme is
      indistinguishable from the enzyme purified directly from Vibrio. To obtain
      mutants exhibiting higher stability in organic solvents, random mutations were
      introduced by error-prone PCR and 600 transformants were screened. The N123D
      mutant exhibits two times higher stability in organic solvents than the wild-type
      enzyme. A plausible mechanism for the stability of the N123D mutant in organic
      solvents was discussed based on homology models of vimelysin and the N123D
      mutant.

PMID- 16428300
TI  - Link between the ubiquitin conjugation system and the ISG15 conjugation system:
      ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme.
AB  - ISG15 is a ubiquitin-like protein that is upregulated on treatment with
      interferon. ISG15 is considered to be covalently conjugated to cellular proteins
      through a sequential reaction similar to that of the ubiquitin conjugation system
      consisting of E1/E2/E3 enzymes: UBE1L and UbcH8 have been reported to function as
      E1 and E2 enzymes, respectively, for ISG15 conjugation. Several cellular proteins
      have been identified as targets for ISG15 conjugation, but the roles of ISG15
      conjugation remain unclear. In this study, we found that UbcH6 and UbcH8, E2
      enzymes for ubiquitin conjugation, are covalently modified by ISG15. We also
      found that UbcH6 is capable of forming a thioester intermediate with ISG15
      through Cys131. We determined that the Lys136 residue near the catalytic site
      Cys131 is the ISG15 conjugation site in UbcH6. We isolated ISG15-modified and
      unmodified UbcH6 proteins, and analyzed their abilities to form thioester
      intermediates with ubiquitin. A ubiquitin thioester intermediate was detected in
      the case of unmodified UbcH6, but not in that of ISG15-modified UbcH6, strongly
      suggesting that ISG15 conjugation to UbcH6 suppresses its ubiquitin E2 enzyme
      activity. Thus, we provide evidence for a link between the ubiquitin conjugation
      system and the ISG15 conjugation system.

PMID- 16428301
TI  - Involvement of EDTP, an egg-derived tyrosine phosphatase, in the early
      development of Drosophila melanogaster.
AB  - Previously, we purified a novel protein tyrosine phosphatase from eggs of the
      flesh fly, Sarcophaga peregrina. This protein tyrosine phosphatase, named egg
      derived tyrosine phosphatase (EDTP), is expressed during oogenesis and early
      embryogenesis but is rapidly degraded in middle embryogenesis by lysosomal
      cathepsin L. Here, we demonstrate the requirement of EDTP in the development of
      the fruit fly, Drosophila melanogaster. Deletion of the Drosophila EDTP gene
      using transposase-catalyzed imprecise excision resulted in homozygous lethals
      during embryogenesis. Additionally, germline clones generated using the FLP-FRT
      ovo(D) system showed severe defects in ovarian development during oogenesis.
      These results indicate that the Drosophila EDTP gene is crucial in oogenesis and
      embryogenesis.

PMID- 16428302
TI  - Interaction analysis between tmRNA and SmpB from Thermus thermophilus.
AB  - Small protein B, SmpB, is a tmRNA-specific binding protein essential for trans
      translation. We examined the interaction between SmpB and tmRNA from Thermus
      thermophilus, using biochemical and NMR methods. Chemical footprinting analyses
      using full-length tmRNA demonstrated that the sites protected upon SmpB binding
      are located exclusively in the tRNA-like domain (TLD) of tmRNA. To clarify the
      SmpB binding sites, we constructed several segments derived from TLD. Optical
      biosensor interaction analyses and melting profile analyses with mutational
      studies showed that SmpB efficiently binds to only a 30-nt segment that forms a
      stem and loop, with the 5' and 3' extensions composed of the D-loop and variable
      loop analogues. The conserved sequences, 16UCGA and 319GAC, in the extensions are
      responsible for the SmpB binding. These results agree with the those visualized
      by the cocrystal structure of TLD and SmpB from Aquifex aeolicus. In addition,
      NMR chemical shift mapping analyses, using the 30-nt segment and (15)N-labeled
      SmpB, revealed the characteristic RNA binding mode. The hydrogen bond pattern
      around beta2 changes, with the Gly in beta2, which acts as a hinge, showing the
      largest chemical shift change. It appears that SmpB undergoes structural changes
      indicating an induced fit upon binding to the specific region of TLD.

PMID- 16428303
TI  - Recognition site for the side chain of 2-ketoacid substrate in d-lactate
      dehydrogenase.
AB  - Replacement of Tyr52 with Val or Ala in Lactobacillus pentosus d-lactate
      dehydrogenase induced high activity and preference for large aliphatic 2
      ketoacids and phenylpyruvate. On the other hand, replacements with Arg, Thr or
      Asp severely reduced the enzyme activity, and the Tyr52Arg enzyme, the only one
      that exhibited significant enzyme activity, showed a similar substrate preference
      to the Tyr52Val and Tyr52Ala enzymes. Replacement of Phe299 with Gly or Ser
      greatly reduced the enzyme activity with less marked change in the substrate
      preference. Except for the Phe299Ser enzyme, these mutant enzymes with low
      catalytic activity consistently stimulated NADH oxidation in the absence of 2
      ketoacid substrates. However, the double mutant enzymes, Tyr52Arg/Phe299Gly and
      Tyr52Thr/Phe299Ser, did not exhibit synergically decreased enzyme activity or the
      substrate-independent NADH oxidation, but rather increased activities toward
      certain 2-ketoacid substrates. These results indicate that the coordinative
      combination of amino acid residues at two positions is pivotal in both the
      functional recognition of the 2-ketoacid side chain and the protection of the
      bound NADH molecule from the solvent. Multiplicity in such combinations appears
      to provide d-LDH-related 2-hydroxyacid dehydrogenases with a great variety of
      catalytic and physiological functions.

PMID- 16428304
TI  - Selective perturbation of the intravesicular heme center of cytochrome b561 by
      cysteinyl modification with 4,4'-dithiodipyridine.
AB  - Cytochrome b(561) from bovine adrenal chromaffin vesicles contains two hemes b
      with EPR signals at g(z) = 3.69 and 3.14 and participates in transmembrane
      electron transport from extravesicular ascorbate to an intravesicular
      monooxygenase, dopamine beta-hydroxylase. Treatment of purified cytochrome b(561)
      in an oxidized state with a sulfhydryl reagent, 4,4'-dithiodipyridine, caused the
      introduction of only one 4-thiopyridine group per b(561) molecule at either Cys57
      or Cys125. About half of the heme centers of the modified cytochrome were reduced
      rapidly with ascorbate as found for the untreated sample, but the final reduction
      level decreased to approximately 65%. EPR spectra of the modified cytochrome
      showed that a part of the g(z) = 3.14 low-spin EPR species was converted to a new
      low-spin species with g(z) = 2.94, although a considerable part of the heme
      center was concomitantly converted to a high-spin g = 6 species. Addition of
      ascorbate to the modified cytochrome caused the disappearance or significant
      reduction of the EPR signals at g(z) = 3.69 and 3.14 of low-spin species and at g
      = 6.0 of the high-spin species, but not for the g(z) approximately 2.94 species.
      These results suggested that the bound 4-thiopyridone at either Cys57 or Cys125
      affected the intravesicular heme center and converted it partially to a non
      ascorbate-reducible form. The present observations suggested the importance of
      the two well-conserved Cys residues near the intravesicular heme center and
      implied their physiological roles during the electron donation to the
      monodehydroascorbate radical.

PMID- 16428305
TI  - Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII
      like protein.
AB  - We cloned cDNA and genomic DNA containing exon 1 of mouse Neil3. Neil3 spans 52.4
      kb and consists of 10 exons. Northern blot analysis revealed that Neil3 mRNA was
      selectively expressed in thymus, spleen and bone marrow. High levels of Neil3
      mRNA were also detected in various mouse B cell lines by RT-PCR.
      Immunofluorescence microscopy using anti-NEIL3 revealed that recombinant mouse
      NEIL3 is localized in the nuclei. In mouse splenocytes, the level of Neil3 mRNA
      significantly increased after mitogen stimulation in vitro. We established NEIL3
      null mice, which are viable and fertile. We found candidate sequences for NEIL3
      orthologues in a DNA database from dog and zebrafish in addition to human and
      mouse, but not invertebrates. NEIL3 may function exclusively in vertebrates, such
      as mammals.

PMID- 16428307
TI  - Identification of Pex5pM, and retarded maturation of 3-ketoacyl-CoA thiolase and
      acyl-CoA oxidase in CHO cells expressing mutant Pex5p isoforms.
AB  - Recently, we isolated CHO cells, termed SK32 cells, that express mutant Pex5p
      (G432R), and showed mislocalization of catalase in the cytosol, but peroxisomal
      localization of 3-ketoacyl-CoA thiolase (thiolase) in the mutant cells [Ito, R.
      et al. (2001) Biochem. Biophys. Res. Commun. 288, 321-327]. While analyzing the
      mutant cells, we found a novel Pex5p isoform (Pex5pM), which was shorter by seven
      amino acids than Pex5pL and longer by 30 amino acids than Pex5pS. Similar levels
      of mRNA syntheses for the PEX5 gene were observed in both the wild type and
      mutant cells, but the protein levels of Pex5p isoforms were markedly reduced in
      the mutant cells cultured at 37 degrees C and only slightly discernible at 30
      degrees C, suggesting that they could be rapidly degraded. Furthermore, we
      characterized the peroxisomal localization of thiolase and acyl-CoA oxidase (Aox)
      in SK32 cells. The proteins in the organelle fraction were protected from
      proteinase K-digestion in the mutant cells, indicating that they were
      translocated inside peroxisomes. However, the conversion of Aox from component A
      to components B and C was completely prevented at both 30 and 37 degrees C, and
      the precursor form of thiolase was partially processed to the mature one in a
      temperature-sensitive manner. Transformed SK32 cells stably expressing one of the
      wild type Pex5p isoforms were isolated, and then the maturation steps for
      thiolase and Aox were examined. Pex5pM and S restored the processing of the two
      enzymes, but Pex5pL did not. In addition, Pex5pL prevented the maturation of
      thiolase observed at 30 degrees C. These results indicate that (i) the novel
      Pex5pM is functional and (ii) a seven amino acids-insertion, which is present in
      the L isoform but absent in the M isoform, plays some role in the process of
      maturation of thiolase and Aox.

PMID- 16428306
TI  - Cooperation of ER-60 and BiP in the oxidative refolding of denatured proteins in
      vitro.
AB  - ER-60 is a PDI family protein that has protein thiol-disulfide oxidoreductase
      activity. It has been shown to associate with BiP in the endoplasmic reticulum.
      Here, we analyzed the cooperation of ER-60 and BiP in the oxidative refolding of
      denatured proteins in vitro. ER-60 facilitated the refolding of 20 or 30% of
      denatured alpha-lactalbumin or ribonuclease B during incubation for 80 min, and
      these levels of nearly doubled on the addition of BiP to the reaction mixture.
      BiP alone could not refold denatured ribonuclease B, but could refold denatured
      alpha-lactalbumin a little. Enhancement of oxidative refolding of alpha
      lactalbumin by ER-60 could be detected only when ER-60 was present from the start
      of refolding. On surface plasmon resonance analysis, ER-60 was shown to associate
      with BiP. The association was not influenced by ATP or ADP. Domains a and/or b'
      of ER-60 were implicated in the association with BiP.

PMID- 16428308
TI  - Affinity-tagged phosphorylation assay by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (ATPA-MALDI): application
      to calcium/calmodulin-dependent protein kinase.
AB  - A matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS)-based kinase assay using a peptide substrate tagged with a
      biotinyl group has been developed. The peptide moiety was designed to serve as an
      efficient substrate for calcium/calmodulin-dependent protein kinase II, based on
      the in vivo phosphorylation site of phosrestin I, a Drosophila homolog of
      arrestin. In the assay, the quantitative relationship was determined from the
      ratio of the peak areas between the two peaks respectively representing the
      unphosphorylated and the phosphorylated substrate. Attempts to assay
      phosphorylated peptides directly from the reaction mixture, gave inaccurate
      results because of the high noise level caused by the presence of salts and
      detergents. In contrast, after purifying the substrate peptides with the biotin
      affinity tag using streptavidin-coated magnetic beads, peak areas accurately
      represented the ratio between the unphosphorylated and phosphorylated peptide. By
      changing the substrate peptide to a peptide sequence that serves as a kinase
      substrate, it is expected that an efficient non-radioactive protein kinase assay
      using MALDI-TOF MS can be developed for any type of protein kinase. We call this
      technique "Affinity-Tagged Phosphorylation Assay by MALDI-TOF MS (ATPA-MALDI)."
      ATPA-MALDI should serve as a quick and efficient non-radioactive protein kinase
      assay by MALDI-TOF MS.

PMID- 16428310
TI  - Role of the basic C-terminal half of caldesmon in its regulation of F-actin:
      comparison between caldesmon and calponin.
AB  - We previously reported that caldesmon (CaD), together with tropomyosin (TM),
      effectively protects actin filaments from gelsolin, an actin-severing protein. To
      elucidate the structure/function relationship of CaD, we dissected the functional
      domain of CaD required for the protection. The basic C-terminal half of rat
      nonmuscle CaD (D3) inhibits gelsolin activity to the same degree as intact CaD,
      although a smaller C-terminal region of D3 does not. This smaller C-terminal
      region contains the minimum regulatory domain responsible for the inhibition of
      actomyosin ATPase, and for the binding to actin, calmodulin and TM. These results
      suggest that the domain responsible for the inhibition of gelsolin activity lies
      outside the minimum regulatory domain, and that the positive charge possessed by
      the C-terminal half of CaD is important for its interaction with actin. Moreover,
      while the D3 fragment promotes the aggregation of F-actin into bundles as
      reported previously, this bundle formation is inhibited by the acidic N-terminal
      half of CaD, as well as by poly-l-glutamate. It seems likely that the acidic N
      terminal half of CaD neutralizes the superfluous basic feature of the C-terminal
      half. A comparison between D3 and calponin, another actin-binding protein that is
      also basic and has similar actin-regulatory activities, is also discussed.

PMID- 16428309
TI  - Effects of four oxidants, menadione, 1-chloro-2,4-dinitrobenzene, hydrogen
      peroxide and cumene hydroperoxide, on fission yeast Schizosaccharmoyces pombe.
AB  - Several chemical agents have been used to exert oxidative stress in the study of
      stress response, but differences in the effects of different reagents have
      received little attention. To elucidate whether such differences exist, the
      response of Schizosaccharomyces pombe to menadione (MD), 1-chloro-2,4
      dinitrobenzene (CDNB), hydrogen peroxide and cumene hydroperoxide (CHP), which
      are frequently used to exert oxidative stress, was investigated. Sensitivity to
      these reagents differed among mutants deficient in genes involved in oxidative
      stress resistance. N-Acetylcysteine restored resistance to MD, CHP and hydrogen
      peroxide but did not change sensitivity to CDNB. The induction kinetics of genes
      induced by oxidative stress differed for each reagent. MD, CDNB and hydrogen
      peroxide caused a transient induction of genes, but the peak times of induction
      differed among the reagents. CHP gave quite different kinetics in that the
      induction continued for up to 2 h. The ctt1(+) gene was not induced by CHP. GSH
      rapidly decreased in the cells treated with high concentrations of these
      reagents, but at a low concentration only CDNB decreased GSH. These results
      indicated that S. pombe responded differently to the oxidative stress exerted by
      these different reagents.

PMID- 16428311
TI  - Identification of the region responsible for fibril formation in the CAD domain
      of caspase-activated DNase.
AB  - Caspase-activated DNase (CAD) has a compact domain at its N-terminus (CAD domain,
      87 amino acid residues), which comprises one alpha-helix and five beta-strands
      forming a single sheet. The CAD domain of CAD (CAD-CD) forms amyloid fibrils
      containing alpha-helix at low pH in the presence of salt. To obtain insights into
      the mechanism of amyloid fibril formation, we identified the peptide region
      essential for fibril formation of CAD-CD and the region responsible for the salt
      requirement. We searched for these regions by constructing a series of deletion
      and point mutants of CAD-CD. Fibril formation by these CAD-CD mutants was
      examined by fluorescence analysis of thioflavin T and transmission electron
      microscopy. C-Terminal deletion and point mutation studies revealed that an
      aromatic residue near the C-terminus (Trp81) is critical for fibril formation. In
      addition, the main chain conformation of the beta5 strand, which forms a
      hydrophobic core with Trp81, was found to be important for the fibril formation
      by CAD-CD. The N-terminal 30 amino acid region containing two beta-strands was
      not essential for fibril formation. Rather, the N-terminal region was found to be
      responsible for the requirement of salt for fibril formation.

PMID- 16428312
TI  - Structural similarity between histone chaperone Cia1p/Asf1p and DNA-binding
      protein NF-kappaB.
AB  - The structural relationships between histone-binding proteins and DNA-binding
      proteins are important, since nucleosome-interacting factors possess histone
      binding and/or DNA-binding components. S. cerevisiae (Sc) Cia1p/Asf1p, a
      homologue of human CIA (CCG1-interacting factor A), is the most evolutionarily
      conserved histone chaperone, which facilitates nucleosome assembly by interacting
      with the nucleosome entry site of the core histones H3/H4. The crystal structure
      of the evolutionarily conserved domain (residues 1-169) of Cia1p (ScCia1p
      DeltaC2) was determined at 2.95 A resolution. The refined model contains 166
      residues in the asymmetric unit. The overall tertiary structure resembles a beta
      sandwich fold, and belongs to the "switched" immunoglobulin class of proteins.
      The crystal structure suggests that ScCia1p-DeltaC2 is structurally related to
      the DNA-binding proteins, such as NF-kappaB and its family members. This is the
      first examination of the structural similarities between a histone chaperone and
      DNA-binding proteins. We discuss the possibilities that the strands beta3 and
      beta4, which possess highly electronegative surface potentials, are the important
      regions for the interaction with core histones, and that the histone chaperone
      ScCia1p/Asf1p and the DNA-binding protein NF-kappaB may have evolved from the
      same prototypal protein class.

PMID- 16428313
TI  - Aminopropyltransferases: function, structure and genetics.
AB  - Aminopropyltransferases use decarboxylated S-adenosylmethionine as an aminopropyl
      donor and an amine acceptor to form polyamines. This review covers their
      structure, mechanism of action, inhibition, regulation and function. The best
      known aminopropyltransferases are spermidine synthase and spermine synthase but
      other members of this family including an N(1)-aminopropylagmatine synthase have
      been characterized. Spermidine synthase is an essential gene in eukaryotes and is
      very widely distributed. Key regions in the active site, which are very highly
      conserved, were identified by structural studies with spermidine synthase from
      Thermotoga maritima bound to S-adenosyl-1,8-diamino-3-thiooctane, a
      multisubstrate analog inhibitor. A general mechanism for catalysis by
      aminopropyltransferases can be proposed based on these studies. Spermine synthase
      is less widely distributed and is not essential for growth in yeast. However, Gy
      mice lacking spermine synthase have multiple symptoms including a profound growth
      retardation, sterility, deafness, neurological abnormalities and a propensity to
      sudden death, which can all be prevented by transgenic expression of spermine
      synthase. A large reduction in spermine synthase in human males due to a splice
      site variant causes Snyder-Robinson syndrome with mental retardation, hypotonia
      and skeletal abnormalities.

PMID- 16428314
TI  - Polyamine Modulon in Escherichia coli: genes involved in the stimulation of cell
      growth by polyamines.
AB  - We have recently proposed an idea to explain how polyamines enhance cell growth
      in Escherichia coli. Since most polyamines exist as polyamine-RNA complexes, our
      idea is that polyamines stimulate several kinds of protein synthesis which are
      important for cell growth at the level of translation. We found that synthesis of
      oligopeptide binding protein (OppA), which is important for nutrient supply,
      adenylate cyclase (Cya), RNA polymerase sigma(38) subunit (RpoS), transcription
      factor of iron transport operon (FecI), and transcription factor of growth
      related genes including rRNA and some kinds of tRNA synthesis (Fis) was enhanced
      by polyamines at the level of translation. We proposed that a group of genes
      whose expression is enhanced by polyamines at the level of translation be
      referred to as a "polyamine modulon." By DNA microarray, we found that 309 of
      2,742 mRNA species were up-regulated by polyamines. Among the 309 up-regulated
      genes, transcriptional enhancement of at least 58 genes might be attributable to
      increased levels of the transcription factors Cya, RpoS, FecI, and Fis. This
      unifying molecular mechanism is proposed to underlie the physiological role of
      polyamines in controlling the growth of Escherichia coli.

PMID- 16428316
TI  - Emerging concepts in targeting the polyamine metabolic pathway in epithelial
      cancer chemoprevention and chemotherapy.
AB  - The polyamines are important molecules governing cell proliferation, survival and
      apoptosis. Consistent with their elevated levels in cancer, they have been shown
      to mediate tumor promotion and progression. Cellular and tissue polyamine pools
      and metabolic flux are regulated by a number of processes. Neoplastic
      transformation is accompanied with an increase in biosynthesis, decreased
      catabolism and elevated uptake of exogenous polyamines. Effective strategies for
      cancer chemoprevention and chemotherapy, targeting the polyamine metabolic
      pathway will likely require a combination of agents acting at multiple sites of
      this pathway. Genetic variability affecting expression of the ornithine
      decarboxylase gene suggests an association between ODC expression and cancer
      risk, and prediction of response to treatment in certain epithelial cancers.

PMID- 16428317
TI  - A palindromic repeat sequence adopts a stable fold back structure under
      supercoiling.
AB  - A synthetic deoxyoligonucleotide containing five palindromic repeats of GGATCC
      self assembles to form a parallel four-stranded structure held together by G
      tetrads that shows slower mobility than duplex DNA. This structure is
      hypersensitive to S1 nuclease and resistant to DMS modification. The same
      oligonucleotide when cloned in a plasmid forms a different structure under
      supercoiling that persists stably even in the cleaved out insert. On
      polyacrylamide gel electrophoresis, the cleaved out insert moves to a position
      midway between the duplex and parallel four-stranded forms of the
      oligonucleotide. Upon S1 nuclease treatment, the cleaved out insert shows a
      discreet band of 18 base pairs, suggesting an unfolded region in the middle. All
      the guanines in the cleaved out insert are sensitive to DMS modification and
      produce a positive peak at 285 nM in the circular dichroism spectrum, a signature
      of fold back tetraplex structures. We propose a fold back quadruplex structure
      for the insert under supercoiling with only A.T.A.T and G.C.G.C tetrads. This is
      the first suggestive evidence of a general tetraplex motif without G quartets as
      that proposed for generalized recombination.

PMID- 16428315
TI  - Mammalian polyamine catabolism: a therapeutic target, a pathological problem, or
      both?
AB  - With the recent discovery of the polyamine catabolic enzyme spermine oxidase
      (SMO/PAOh1), the apparent complexity of the polyamine metabolic pathway has
      increased considerably. Alone or in combination with the two other known members
      of human polyamine catabolism, spermidine/spermine N(1)-acetyltransferase, and
      N(1)-acetylpolyamine oxidase (PAO), SMO/PAOh1 expression has the potential to
      alter polyamine homeostasis in response to normal cellular signals, drug
      treatment and environmental and/or cellular stressors. The activity of the
      oxidases producing toxic aldehydes and the reactive oxygen species (ROS)
      H(2)O(2), suggest a mechanism by which these oxidases can be exploited as an
      antineoplastic drug target. However, inappropriate activation of the pathways may
      also lead to pathological outcomes, including DNA damage that can lead to
      cellular transformation. The most recent data suggest that the two polyamine
      catabolic pathways exhibit distinct properties and understanding these properties
      should aid in their exploitation for therapeutic and/or chemopreventive
      strategies.

PMID- 16428318
TI  - Effects of ionic strength on the thermal unfolding process of granulocyte-colony
      stimulating factor.
AB  - This paper reports the effect of ionic strength on the process of thermal
      unfolding of recombinant methionyl human granulocyte-colony stimulating factor
      (rmethuG-CSF) at acid pH. We previously reported that the protein aggregates were
      formed at the highest temperature at pD 2.1 in the pD range of 5.5-2.1 and that
      the aggregation proceeded a little at pD 2.1 because of the strong repulsive
      interaction between the unordered structures that play the role of a precursor
      for the aggregation. In the present study temperature-dependent IR spectra and
      far-UV CD spectra were measured for rmethuG-CSF in aqueous solutions containing
      various concentrations of NaCl at acid pH. Second derivative and curve-fitting
      analysis were performed to examine the obtained IR spectra. The results revealed
      that the structure of rmethuG-CSF becomes less stable with increasing ionic
      strength at all pDs investigated (pD 2.1, 2.5, and 4.0). We have also
      demonstrated that, at pD 2.1, the temperature at which the protein aggregation
      starts becomes lower and that the amount of the aggregates becomes larger with
      the addition of NaCl. This is probably because the addition of NaCl masks the
      repulsive electrostatic interaction between the unordered structures.

PMID- 16428319
TI  - Drosophila damaged DNA binding protein 1 contributes to genome stability in
      somatic cells.
AB  - The damaged DNA-binding protein (DDB) complex consists of a heterodimer of p127
      (DDB1) and p48 (DDB2) subunits and is believed to have a role in nucleotide
      excision repair (NER). We used the GAL4-UAS targeted expression system to knock
      down DDB1 in wing imaginal discs of Drosophila. The knock-down was achieved in
      transgenic flies using over-expression of inverted repeat RNA of the D-DDB1 gene
      [UAS-D-DDB1(650)-dsRNA]. As a consequence of RNA interference (RNAi), the fly had
      a shrunken wing phenotype. The wing spot test showed induced genome instability
      in transgenic flies with RNAi knock-down of D-DDB1 in wing imaginal discs. When
      Drosophila larvae with RNAi knock-down of D-DDB1 in wing imaginal discs were
      treated with the chemical mutagen methyl methanesulfonate (MMS), the frequency of
      flies with a severely shrunken wing phenotype increased compared to non-treated
      transgenic flies. These results suggested that DDB1 plays a role in the response
      to DNA damaged with MMS and in genome stability in Drosophila somatic cells.

PMID- 16428320
TI  - Characterization of hyaluronan-binding proteins on guinea pig polymorphonuclear
      leukocytes: possible involvement of complement receptor type 3 (CR3, CD11b/CD18)
      in the hyaluronan-leukocyte interaction.
AB  - Hyaluronan (HA), a high-molecular-weight glycosaminoglycan ubiquitously present
      in the extracellular matrices (ECMs) of animals, plays important roles in ECM
      organization and cell behavior through binding to hyaluronan-binding proteins
      (HABPs). We previously reported that HA has anti-inflammatory effects on guinea
      pig phagocytes, although the nature of guinea pig HABPs was unknown. In this
      study, we characterized guinea pig HABPs on peritoneal polymorphonuclear
      leukocytes (PMNs) and blood neutrophils by flow cytometry and affinity
      chromatography. It was found that PMNs express diverse HABPs with different
      molecular weights. These HABPs maximally bound with HA over a wide pH range (6
      8), and recognized HAs as small as the pentadisaccharide units of d-glucuronic
      acid and N-acetyl-d-glucosamine. Furthermore, they could be divided into Mg(2+)
      dependent and Ca(2+)/Mg(2+)-independent groups. Interestingly, two proteins in
      the Mg(2+)-dependent group were found to be the two subunits of complement
      receptor type 3 (CR3, CD11b/CD18). Unlike PMNs, blood neutrophils expressed
      several functionally inactive HABPs. Among these inactive HABPs, Mg(2+)-dependent
      proteins including CR3 but not Ca(2+)/Mg(2+)-independent proteins were activated
      on phorbol ester-stimulation. These results show the existence of diverse HABPs
      on guinea pig neutrophils and the cell activation-dependent activation of HABPs.
      It is also suggested that the CR3-HA interaction is possibly involved in the
      regulation of neutrophil function.

PMID- 16428322
TI  - Decrease in polyamines with aging and their ingestion from food and drink.
AB  - Changes in polyamine levels during aging were measured in 3-, 10- and 26-week-old
      female mice. The level of polyamines in pancreas, brain, and uterus was
      maintained during these periods. The level of spermidine slightly decreased in
      intestine, and decreased significantly in thymus, spleen, ovary, liver, stomach,
      lung, kidney, heart and muscle during these periods. In skin, the level of
      spermidine was maximal in 10-week-old mice and markedly reduced in 26-week-old
      mice. The results suggest that maintenance of polyamine levels may play important
      roles in the function of the pancreas, brain and uterus in 3- to 26-week-old
      mice. We next looked for polyamine-rich food materials as a dietary source of
      polyamines. Foods found to be rich in polyamines included wheat germ, rice bran,
      black rice, Philippine mango, green pepper, Japanese pumpkin, nuts, fermented
      pickles, pond smelt, turban shell viscera, whelk viscera, salted salmon roe,
      salted cod roe, beef intestine (boiled) and liver of eel, beef, pork and chicken;
      and, as previously reported, soybean, fermented soybean (natto), mushrooms,
      orange and green tea leaf. These results offer useful information when it becomes
      necessary to ingest polyamines from food.

PMID- 16428321
TI  - A proteomic assessment of muscle contractile alterations during unloading and
      reloading.
AB  - Unloading of skeletal muscle causes atrophy and altered contractility. To
      identify major muscle proteins responding significantly to the altered loading
      and to elucidate how the contractile alterations reflect potential proteomic
      modifications, we examined protein expression in the rat soleus muscle during 3
      week hindlimb suspension and 2-week reloading. Compared with unsuspended
      controls, experimental animals had a 0.5- to 0.6-fold decrease in tension during
      unloading and early reloading, comparable to 0.2- to 0.6-fold decreases in the
      protein levels of myosin light chain 1 (MLC1), alpha-actin, tropomyosin beta
      chain, and troponins T1 and T2. The observed 1.4- to 1.6-fold increase in
      shortening velocity appears to reflect 1.2- to 9.0-fold increases in the protein
      levels of fast-type MLC2, glycolytic enzymes, and creatine kinase, and 0.2- to
      0.3-fold decreases in slow-type troponins T1 and T2. The levels of three heat
      shock proteins (p20, alpha crystallin B chain, and HSP90) decreased during
      unloading but returned to control levels during reloading. These results imply
      that proteomic responses to unloading change overall myofibrillar integrity and
      metabolic regulation, resulting in altered contractility.

PMID- 16428323
TI  - PKCI-W forms a heterodimer with PKCI-Z and inhibits the biological activities of
      PKCI-Z in vitro, supporting the predicted role of PKCI-W in sex determination in
      birds.
AB  - The two chicken genes, PKCI-W on the W chromosome and PKCI-Z on the Z chromosome,
      belong to the gene family encoding the Hint (histidine triad nucleotide-binding
      protein)-branch proteins in the widely conserved HIT (histidine triad)-family. It
      has been speculated that PKCI-W is involved in the sex determination of birds by
      forming a heterodimer with PKCI-Z and inhibiting the function of PKCI-Z in female
      embryos. In this study, both PKCI-W and PKCI-Z were expressed in fusion [maltose
      binding protein (MBP) or glutathione-S-transferase (GST)] and tagged [(His)(6) or
      FLAG] forms (FT-forms) in Escherichia coli and purified. Formation of homodimers
      of PKCI-W-containing or the PKCI-Z-containing FT-protein and the formation of a
      heterodimer between the PKCI-W-containing and the PKCI-Z-containing FT-proteins
      were demonstrated by Western blotting after GST-pulldown or binding to and
      elution from the Co(2+)-resin. The homodimer of PKCI-Z, but not PKCI-W, bound to
      an N(6)-(3- aminopropyl) adenosine affinity column and hydrolyzed adenosine 5'
      monophosphoramidate. Both of these activities were inhibited in vitro in a
      dominant-negative manner by the formation of a heterodimer containing PKCI-W.
      These in vitro experimental results support the predicted role of PKCI-W in the
      process of sex determination in birds.

PMID- 16428324
TI  - A higher plant has three different types of RPA heterotrimeric complex.
AB  - Replication protein A (RPA) is a protein complex composed of three subunits known
      as RPA70, RPA32, and RPA14. Generally, only one version of each of the three RPA
      genes is present in animals and yeast (with the exception of the human RPA32
      ortholog). In rice (Oryza sativa L.), however, two paralogs of RPA70 have been
      reported. We screened the rice genome for RPA subunit genes, and identified three
      OsRPA70 (OsRPA70a, OsRPA70b and OsRPA70c), three OsRPA32 (OsRPA32-1, OsRPA32-2
      and OsRPA32-3), and one OsRPA14. Through two-hybrid assays and pull down
      analyses, we showed that OsRPA70a interacted preferentially with OsRPA32-2,
      OsRPA70b with OsRPA32-1, and OsRPA70c with OsRPA32-3. OsRPA14 interacted with all
      OsRPA32 paralogs. Thus, rice has three types of RPA complex: OsRPA70a-OsRPA32-2
      OsRPA14 (type A), OsRPA70b-OsRPA32-1-OsRPA14 (type B), and OsRPA70c-OsRPA32-3
      OsRPA14 (type C). Subcellular localization analysis suggested that the type-A RPA
      complex is required for chloroplast DNA metabolism, whereas types B and C
      function in nuclear DNA metabolism.

PMID- 16428325
TI  - A novel yeast-based reporter assay system for the sensitive detection of
      genotoxic agents mediated by a DNA damage-inducible LexA-GAL4 protein.
AB  - Yeast-based genotoxicity testing systems can sensitively detect DNA damaging
      agents in the environment. We have developed a novel "indirect" reporter assay
      system based on a recombinant yeast containing both a sensor and a reporter
      plasmid. The sensor plasmid contains a gene encoding the artificial transcription
      factor of the Escherichia coli LexA DNA binding domain fused to the
      transcriptional activation domain of yeast Gal4p, which is regulated by the DNA
      damage-inducible RNR2 promoter. The reporter plasmid contains the E. coli lacZ
      gene with the LexA binding site in the 5'-upstream region, allowing
      transcriptional activation by the induced LexA-GAL4 protein. The activity of DNA
      damage-dependent beta-galactosidase (beta-gal) in the "indirect" reporter assay
      system was compared with that of a current yeast-based "direct" reporter system.
      The "indirect" system exhibited 1.5- to 5-fold greater beta-gal activity upon
      induction by alkylating agents or camptothecin. To increase the sensitivity of
      the new reporter system further, several deletion yeast strains were tested, and
      enhanced induction of reporter activity was observed in DNA repair-deficient
      mag1Delta cells. The "indirect" 96-well microtiter plate assay system is a
      potentially inexpensive and sensitive method for detecting genotoxic activities
      in a wide range of compounds, and in polluted environmental samples.

PMID- 16428326
TI  - Regulation of polar flagellar number by the flhF and flhG genes in Vibrio
      alginolyticus.
AB  - The number and location of bacterial flagella vary with the species. The Vibrio
      alginolyticus cell has a single polar flagellum, which is driven by sodium ions.
      We selected mutants on the basis of reduced swarming ability on soft agar plates.
      Among them, we found two mutants with multiple polar flagella, and named them
      KK148 and NMB155. In Pseudomonas species, it is known that FlhF and FleN, which
      are FtsY and MinD homologs, respectively, are involved in regulation of flagellar
      placement and number, respectively. We cloned homologous genes of V.
      alginolyticus, flhF and flhG. KK148 cells had a nonsense mutation in flhG; cells
      expressing transgenic flhG recovered the swarming ability and had a reduced
      number of polar flagella. NMB155 cells did not have a mutation in either flhF or
      flhG. In wild-type cells, expression of flhF increased the number of polar
      flagella; in contrast, expression of flhG reduced both the number of polar
      flagella and the swarming ability. These results suggest that FlhG negatively
      regulates the number of polar flagella in V. alginolyticus. KK148 cells
      expressing both flhF and flhG exhibited fewer polar flagella and better swarming
      ability than KK148 cells expressing flhG alone, suggesting that FlhG acts with
      FlhF.

PMID- 16428327
TI  - Use of RNase P for efficient preparation of yeast tRNATyr transcript and its
      mutants.
AB  - Because T7 RNA polymerase has a strong preference for particular sequences to
      initiate transcription, some RNAs having pyrimidine-rich sequences at their 5'
      end (yeast tRNA(Tyr), for example) are hardly transcribed by this enzyme. To
      circumvent this inconvenience, we have developed an efficient method for in vitro
      preparation of such tRNAs. The RNA of interest is first transcribed as a
      precursor form that has purine-rich extra sequences at its 5'-end, then processed
      with RNase P to generate the objective tRNAs. By using this protocol, we were
      able to prepare easily and efficiently yeast tRNA(Tyr) transcript and its mutants
      harboring base substitutions within the anticodon loop and/or acceptor stem
      regions. Aminoacylation analyses of these tRNA transcripts with yeast tyrosyl
      tRNA synthetase revealed that the replacement of G34 by C34 (mutation to amber
      suppressor) severely impaired the aminoacylation, whereas the replacement of the
      U4:G69 wobble base-pair in the acceptor stem region by C4:G69 normal Watson-Crick
      type base-pair improved it.

PMID- 16428328
TI  - Suppression of the mTOR-raptor signaling pathway by the inhibitor of heat shock
      protein 90 geldanamycin.
AB  - Heat shock protein 90 (Hsp90) was co-immunoprecipitated with raptor, the binding
      partner of the mammalian target of rapamycin (mTOR) from HEK293 cells. Hsp90 was
      detected in the anti-raptor antibody immunoprecipitates prepared from the cell
      extract by immunoblot analysis using the anti-Hsp90 antibody, and the association
      of these two proteins was confirmed by immunoprecipitation from the cells co
      expressing Hsp90 and raptor as epitope-tagged molecules. Geldanamycin, a potent
      inhibitor of Hsp90, disrupted the in vivo binding of Hsp90 to raptor without
      affecting the association of raptor and mTOR, and suppressed the phosphorylation
      by mTOR of the downstream translational regulators p70 S6 kinase (S6K) and
      eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). The protein kinase
      activity of S6K as well as the phosphorylation of the substrate, 40S ribosomal
      protein S6, were lowered in the geldanamycin-treated cells. These results
      indicate that Hsp90 is involved in the regulation of protein translation by
      facilitating the phosphorylation reaction of 4E-BP1 and S6K catalyzed by the
      mTOR/raptor complex through the association with raptor, and that the mTOR
      signaling pathway is a novel target of geldanamycin.

PMID- 16428330
TI  - Analysis on the molecular species and concentration of circulating ADAMTS13 in
      Blood.
AB  - ADAMTS13 is the metalloprotease responsible for the proteolytic degradation of
      von Willebrand factor (VWF). A severe deficiency of this VWF-cleaving protease
      activity causes thrombotic thrombocytopenic purpura. This protease, comprising
      1,427 amino acid residues, is composed of multiple domains, i.e., a preproregion,
      a metalloprotease domain, a disintegrin-like domain, a thrombospondin type-1
      motif (Tsp1), a cysteine-rich domain, a spacer domain, seven Tsp1 repeats, and
      two CUB domains. We prepared one polyclonal and seven monoclonal antibodies
      recognizing distinct epitopes spanning the entire ADAMTS13 molecule. Of these
      antibodies, two of the monoclonal ones, which recognize the disintegrin-like and
      cysteine-rich/spacer domains, respectively, abolished the hydrolytic activity of
      ADAMTS13 toward both a synthetic substrate, FRETS-VWF73, and the natural
      substrate, VWF. In addition, these antibodies blocked the binding of ADAMTS13 to
      VWF. These results revealed that the region between the disintegrin-like and
      cysteine-rich/spacer domains interacts with VWF. Employing these established
      polyclonal and monoclonal antibodies, we examined the molecular species of
      ADAMTS13 circulating in the blood by immunoprecipitation followed by Western blot
      analysis, and estimated the plasma concentration of ADAMTS13 by enzyme-linked
      immunosorbent assay. These studies indicated that the major fraction of ADAMTS13
      in blood plasma consisted of the full-length form. The concentration of ADAMTS13
      in normal plasma was approximately 0.5-1 microg/ml.

PMID- 16428329
TI  - MARCH-III Is a novel component of endosomes with properties similar to those of
      MARCH-II.
AB  - MARCH comprises a recently identified family of transmembrane RING-finger
      proteins which is implicated in diverse biological functions, such as immune
      regulation, protein quality control, and membrane trafficking. We previously
      identified MARCH-II, as a binding partner of syntaxin 6, which plays a role in
      endosomal protein transport. In this paper, we describe the cloning and
      characterization of MARCH-III which is the closest homolog of MARCH-II. It is
      broadly expressed at relatively high levels in spleen, colon, and lung. An
      immunofluorescence study of HeLa cells demonstrated that MARCH-III is present in
      peripheral vesicles partially colocalized with transferrin receptor.
      Overexpression of MARCH-III resulted in the redistribution of TGN46 and strong
      inhibition of transferrin uptake. Immunoprecipitation studies revealed that MARCH
      III is associated with syntaxin 6 and MARCH-II. Mutational analyses revealed that
      the PDZ-binding motif and RING finger are essential for the subcellular
      localization of MARCH-III and the inhibitory effect on transferrin uptake. The
      location, associated molecules, and effects of overexpression suggest that MARCH
      III is involved in the regulation of vesicular trafficking in endosomes.

PMID- 16428331
TI  - Profilin and actin-related proteins regulate microfilament dynamics during early
      mammalian embryogenesis.
AB  - BACKGROUND: Profilins are ubiquitous proteins widely distributed in animals,
      including humans. They regulate actin polymerization by sequestering actin
      monomers in association with other actin-related proteins (Arps). Actin
      remodelling is essential for oocyte maturation, fertilization and embryo
      development; yet the role of profilins in these events is not well understood.
      Here we investigate profilin distribution and function during bovine
      fertilization and early embryogenesis, and we examine profilin localization with
      respect to the co-distribution of other Arps. METHODS AND RESULTS: Western
      blotting, confocal microscopy with immunofluorescence and protein inhibition
      studies with antibodies were implemented. Profilin distributes inside interphase
      nuclei, throughout the cytoplasm and near the cell cortex at different stages of
      bovine oocyte maturation, fertilization and embryo development. Expression is
      detected through the blastocyst stage, where profilin localizes to the inner cell
      mass as well as trophectoderm. Profilin co-distributes with actin monomers and
      Arps vasodilator-stimulated phospho protein, p140mDia, Arp 3 and p80 coilin in
      pronucleate-stage zygotes. Antiprofilin antibodies inhibit normal embryo
      development by disrupting microfilaments, but not microtubules, and result in a
      higher concentration of profilin and p140mDia mislocalized to the cortex.
      CONCLUSIONS: These findings demonstrate that profilin regulates actin dynamics
      both within the cytoplasm and inside the nuclei of developing mammalian embryos
      and that its function is essential during fertilization to ensure successful
      development.

PMID- 16428332
TI  - Tyrosine phosphorylation on capacitated human sperm tail detected by
      immunofluorescence correlates strongly with sperm-zona pellucida (ZP) binding but
      not with the ZP-induced acrosome reaction.
AB  - BACKGROUND: Protein tyrosine phosphorylation (TP) of human sperm is related to
      sperm capacitation and zona pellucida (ZP) binding. The aim of this study was to
      determine whether the TP of capacitated sperm is a useful marker for the ability
      of sperm to bind to the ZP and undergo the ZP-induced acrosome reaction (AR).
      METHODS: Semen samples were obtained from 115 subfertile men with sperm count >
      or =20 x 10(6)/ml, motility > or =25% and variable morphology. Motile sperm (2 x
      10(6)/ml) selected by swim-up were incubated with four oocytes for 2 h, and the
      number of sperm bound to the ZP and the ZP-induced AR was examined. TP of sperm
      tail was assessed by immunofluorescence (IF) with anti-phosphotyrosine monoclonal
      antibody. The time course and effects of dibutyryl cyclic adenosine monophosphate
      (dbcAMP) and phorbol myristate acetate (PMA) on TP were also studied. RESULTS: TP
      was stimulated more by dbcAMP (P < 0.001) and less by PMA (P < 0.05). TP
      increased significantly with time of incubation of sperm. TP was not detectable
      on the surface of unfixed live sperm by either Dynabeads or IF. Sperm TP at 2, 4
      and 20 h incubation was all significantly correlated with sperm-ZP binding but
      not with the ZP-induced AR. CONCLUSION: Sperm TP detected by IF correlates
      strongly with sperm-ZP binding capacity but not with the ZP-induced AR. This
      simple IF assay of TP may be a clinically useful test of sperm function that is
      predictive of normal sperm ZP-binding capacity.

PMID- 16428333
TI  - The obstetrical and neonatal outcome of babies born after single-embryo transfer
      in IVF/ICSI compares favourably to spontaneously conceived babies.
AB  - BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal
      outcome of singletons after IVF/ICSI. Because the population of patients
      receiving single-embryo transfer (SET) resulting in singleton pregnancies is
      different from the one that would have become pregnant (with a singleton) before
      SET was introduced, we wanted to investigate whether the outcome of singleton
      pregnancies after SET differed from spontaneously conceived singletons. METHODS:
      The obstetrical and early neonatal outcome of all pregnancies originating from
      SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was
      prospectively collected and analyzed. RESULTS: Data from 251 singleton
      pregnancies and births after SET were analyzed and compared to data from 59,535
      spontaneously conceived singletons retrieved from the Centre for Perinatal
      Epidemiology. The mean birthweight of the singletons after SET was 3322 g (+/-538
      SD) versus 3330 g (+/-531 SD) for the spontaneously conceived singletons (P =
      0.82). The mean gestational age was 38.7 weeks (+/-1.9 SD) for SET and 38.9 weeks
      (+/-1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of
      very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of
      preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous
      singletons (P = 0.03). However, mean birthweight of very preterm, preterm and
      term SET singleton babies was similar to the mean birthweight in every category
      of gestational age in the spontaneous conceived control group. Stillbirth was
      0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in
      whom SET is applied, do not only have a higher chance of conception but do not
      have an unfavourable outcome of their singleton baby when compared to spontaneous
      singletons.

PMID- 16428334
TI  - Management of rare diseases.

PMID- 16428335
TI  - Comparison of prednisolone with piroxicam in complex regional pain syndrome
      following stroke: a randomized controlled trial.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) following stroke aggravates
      morbidity. CRPS is categorized as CRPSI when no clear nerve injury is defined,
      and CRPSII when associated with clear nerve injury. AIM: To compare the effect of
      prednisolone with that of piroxicam in patients with CRPSI following stroke.
      DESIGN: Randomized controlled trial. METHODS: Patients with CRPSI fulfilling the
      inclusion criteria (n = 60) underwent a detailed neurological examination,
      cranial CT scan, radiograph of chest and shoulder joint, blood counts and serum
      chemistry. Severity of stroke was assessed by the Canadian Neurological Scale
      (CNS), CRPS by scoring sensory, autonomic and motor symptoms, and activity of
      daily living by Barthel index (BI) score. Patients were randomly assigned
      prednisolone 40 mg or piroxicam 20 mg daily, and outcome was assessed at 1 month
      on the basis of CRPS and BI score. RESULTS: Mean patient age was 56 years and 20
      were female. Baseline clinical and radiological parameters were comparable
      between the two groups. In the prednisolone group, 83.3% patients showed
      significant improvement, compared to 16.7% in the piroxicam group. The mean
      change in CRPS score in prednisolone group was 6.47 (95%CI 4.37-7.36), whereas in
      piroxicam group it was only 0.47. The mean change in BI score was 7.9 (95%CI 0.82
      5.98) in the prednisolone group, and 4.5 in the piroxicam group. DISCUSSION: In
      this patient group, prednisolone resulted in significant improvement in the
      symptoms and signs of CRPSI following stroke, compared to piroxicam. Both drugs
      produced an improvement in the BI score.

PMID- 16428336
TI  - Fluorescence imaging of cardiac propagation: spectral properties and filtering of
      optical action potentials.
AB  - Fluorescence imaging using voltage-sensitive dyes is an important tool for
      studying electrical propagation in the heart. Yet, the low amplitude of the
      voltage-sensitive component in the fluorescence signal and high acquisition rates
      dictated by the rapid propagation of the excitation wave front make it difficult
      to achieve recordings with high signal-to-noise ratios. Although spatially and
      temporally filtering the acquired signals has become de facto one of the key
      elements of optical mapping, there is no consensus regarding their use. Here we
      characterize the spatiotemporal spectra of optically recorded action potentials
      and determine the distortion produced by conical filters of different sizes. On
      the basis of these findings, we formulate the criteria for rational selection of
      filter characteristics. We studied the evolution of the spatial spectra of the
      propagating wave front after epicardial point stimulation of the isolated,
      perfused right ventricular free wall of the pig heart stained with di-4-ANEPPS.
      We found that short-wavelength (<3 mm) spectral components represent primarily
      noise and surface features of the preparation (coronary vessels, fat, and
      connective tissue). The time domain of the optical action potential spectrum also
      lacks high-frequency components (>100 Hz). Both findings are consistent with the
      reported effect of intrinsic blurring caused by light scattering inside the
      myocardial wall. The absence of high-frequency spectral components allows the use
      of aggressive low-pass spatial and temporal filters without affecting the optical
      action potential morphology. We show examples where the signal-to-noise ratio
      increased up to 150 with <3% distortion. A generalization of our approach to the
      rational filter selection in various applications is discussed.

PMID- 16428337
TI  - Variable ECG signs of ischemia during controlled occlusion of the left and right
      coronary artery in humans.
AB  - Infarct size (IS) increases with vascular occlusion time, area at risk for
      infarction, lack of collateral supply, absence of preconditioning, and myocardial
      demand for O2 supply. ECG S-T segment elevation is used as a measure of severity
      of ischemia and a surrogate for IS. This study in 50 patients with coronary
      artery disease undergoing a first 120-s balloon occlusion of a stenosis sought to
      determine whether S-T segment elevation, corrected for the above-mentioned
      variables, in the left coronary artery (LCA group, n = 36) is different from that
      in the right coronary artery (RCA group, n = 14) territory. After consideration
      of all known determinants of IS, particularly mass at risk and collateral supply,
      the LCA territory is more sensitive than the RCA region to a 2-min period of
      myocardial ischemia.

PMID- 16428338
TI  - Selective matrix metalloproteinase inhibition attenuates progression of left
      ventricular dysfunction and remodeling in dogs with chronic heart failure.
AB  - Matrix metalloproteinases (MMPs) contribute to the progression of left
      ventricular (LV) dysfunction and remodeling associated with heart failure (HF).
      The present study examined the long-term effects of a selective MMP inhibitor PG
      530742 (PG) on the progression of LV dysfunction and remodeling in dogs with HF.
      Chronic HF [LV ejection fraction (LVEF), </=36%] was produced by multiple
      sequential intracoronary microembolizations in 24 dogs. Two weeks after the last
      embolization, dogs were randomized to 3 mo of therapy with either high-dose (HD)
      PG (3.5 mg/kg, n = 8), low-dose (LD) PG (0.2 mg/kg, n = 8), or to a matched
      placebo (PL, n = 8). PG has been shown to produce complete inhibition of MMP-2, 
      3, -9, and -13, while sparing MMPs-1 and -7. Hemodynamic and echocardiographic
      measurements were made before and 3 mo after initiating therapy. In PL and LD
      dogs, LVEF decreased significantly, and LV end-systolic volume (ESV) and LV end
      diastolic volume (EDV) increased significantly during the 3-mo follow-up period.
      Whereas in HD dogs ejection fraction increased from 36 +/- 1 to 40 +/- 1% (P =
      0.003), EDV and ESV decreased (59 +/- 4 vs. 57 +/- 4 ml, P = 0.02; and 38 +/- 2
      vs. 34 +/- 2 ml, P = 0.00001, respectively). When compared with controls, HD
      treated dogs showed 30% reduction in replacement fibrosis, 29% reduction in
      interstitial fibrosis, and 28% reduction in myocyte cross-sectional area. mRNA
      expression of selective MMPs was also reduced in LV tissue in HD- but not LD
      treated dogs. In conclusion, in dogs with moderate HF, long-term monotherapy with
      HD selective MMP inhibitor PG prevents LV remodeling and the progression of
      global LV dysfunction.

PMID- 16428339
TI  - PGE2 stimulates human brain natriuretic peptide expression via EP4 and p42/44
      MAPK.
AB  - Brain natriuretic peptide (BNP) produced by cardiac myocytes has antifibrotic and
      antigrowth properties and is a marker of cardiac hypertrophy. We previously
      showed that prostaglandin E2 (PGE2) is the main prostaglandin produced in
      myocytes treated with proinflammatory stimuli and stimulates protein synthesis by
      binding to its EP4 receptor. We hypothesized that PGE2, acting through EP4, also
      regulates BNP gene expression. We transfected neonatal ventricular myocytes with
      a plasmid encoding the human BNP (hBNP) promoter driving expression of a
      luciferase reporter gene. PGE2 increased hBNP promoter activity 3.5-fold. An EP4
      antagonist reduced the stimulatory effect of PGE2 but not an EP1 antagonist.
      Because EP4 signaling can involve adenylate cyclase, cAMP, and protein kinase A
      (PKA), we tested the effect of H-89, a PKA inhibitor, on PGE2 stimulation of the
      hBNP promoter. H-89 at 5 muM decreased PGE2 stimulation of BNP promoter activity
      by 100%. Because p42/44 MAPK mediates the effect of PGE2 on protein synthesis, we
      also examined the role of MAPKs in the regulation of BNP promoter activity. PGE2
      stimulation of the hBNP promoter was inhibited by a MEK1/2 inhibitor and a
      dominant-negative mutant of Raf, indicating that p42/44 MAPK was involved. In
      contrast, neither a p38 MAPK inhibitor nor a JNK inhibitor reduced the
      stimulatory effect of PGE2. Involvement of small GTPases was also studied.
      Dominant-negative Rap inhibited PGE2 stimulation of the hBNP promoter, but
      dominant-negative Ras did not. We concluded that PGE2 stimulates the BNP promoter
      mainly via EP4, PKA, Rap, and p42/44 MAPK.

PMID- 16428340
TI  - Rapamycin antagonizes NF-kappaB nuclear translocation activated by TNF-alpha in
      primary vascular smooth muscle cells and enhances apoptosis.
AB  - Several lines of evidence support the view that rapamycin inhibits NF-kappaB. TNF
      alpha, a potent inducer of NF-kappaB, is released after artery injury (e.g.,
      balloon angioplasty) and plays an important role in inflammation and restenosis.
      We investigated the effect of rapamycin on NF-kappaB activation and apoptosis in
      vascular smooth muscle cells (VSMCs) stimulated with TNF-alpha. Using EMSA, we
      found that TNF-alpha caused NF-kappaB nuclear translocation in VSMCs after 1 h of
      incubation. Rapamycin inhibited IkappaBalpha degradation, thereby preventing
      nuclear translocation. Activation of NF-kappaB was accompanied by an increase of
      Bcl-xL and Bfl-1/A1 proteins, detected by Western blot assay, whereas rapamycin
      prevented the TNF-alpha-induced enhancement of these antiapoptotic proteins. The
      extent of apoptosis of VSMCs exposed to TNF-alpha was significantly enhanced by
      rapamycin. The effect of rapamycin appeared to be independent of the
      phosphatidylinositol 3-kinase/Akt-protein kinase B survival pathway, because the
      phosphatidylinositol 3-kinase inhibitor wortmannin neither prevented IkappaBalpha
      degradation nor increased apoptosis of cells incubated with TNF-alpha. Finally,
      we demonstrate that the large immunophilin FK-506 binding protein FKBP51 is
      essential for TNF-alpha-induced NF-kappaB activation in VSMCs. Our findings show
      that rapamycin inhibits NF-kappaB activation and acts in concert with TNF-alpha
      in induction of VSMC apoptosis.

PMID- 16428341
TI  - Altered cardiac metabolic phenotype after prolonged inhibition of NO synthesis in
      chronically instrumented dogs.
AB  - Acute inhibition of nitric oxide (NO) synthase causes a reversible alteration in
      myocardial substrate metabolism. We tested the hypothesis that prolonged NO
      synthase inhibition alters cardiac metabolic phenotype. Seven chronically
      instrumented dogs were treated with N(omega)-nitro-L-arginine methyl ester (L
      NAME, 35 mg.kg(-1).day(-1) po) for 10 days to inhibit NO synthesis, and seven
      were used as controls. Cardiac free fatty acid, glucose, and lactate oxidation
      were measured by infusion of [(3)H]oleate, [(14)C]glucose, and [(13)C]lactate,
      respectively. After 10 days of L-NAME administration, despite no differences in
      left ventricular afterload, cardiac O(2) consumption was significantly increased
      by 30%, consistent with a marked enhancement in baseline oxidation of glucose
      (6.9 +/- 2.0 vs. 1.7 +/- 0.5 micromol.min(-1).100 g(-1), P < 0.05 vs. control)
      and lactate (21.6 +/- 5.6 vs. 11.8 +/- 2.6 micromol.min(-1).100 g(-1), P < 0.05
      vs. control). When left ventricular afterload was increased by ANG II infusion to
      stimulate myocardial metabolism, glucose oxidation was augmented further in the L
      NAME than in the control group, whereas free fatty acid oxidation decreased.
      Exogenous NO (diethylamine nonoate, 0.01 micromol.kg(-1).min(-1) iv) could not
      reverse this metabolic alteration. Consistent with the accelerated rate of
      carbohydrate oxidation, total myocardial pyruvate dehydrogenase activity and
      protein expression were higher (38 and 34%, respectively) in the L-NAME than in
      the control group. Also, protein expression of the constitutively active glucose
      transporter GLUT-1 was significantly elevated (46%) vs. control. We conclude that
      prolonged NO deficiency causes a profound alteration in cardiac metabolic
      phenotype, characterized by selective potentiation of carbohydrate oxidation,
      that cannot be reversed by a short-term infusion of exogenous NO. This phenomenon
      may constitute an adaptive mechanism to counterbalance cardiac mechanical
      inefficiency.

PMID- 16428342
TI  - Analysis of effects of connexin-mimetic peptides in rat mesenteric small
      arteries.
AB  - Synthetic peptides homologous to the extracellular loops of the major vascular
      connexins represent a novel class of gap junction blockers that have been used to
      assess the role of direct cellular communication in arteries and veins. However,
      the specificity of action of such peptides on the coupling between smooth muscle
      cells (SMCs) has not yet been fully characterized. Isolated third-order rat
      mesenteric arteries were therefore studied with respect to isometric tension
      (myography), intracellular Ca2+ concentration ([Ca2+]i) (Ca2+ -sensitive dyes),
      membrane potential, and input resistance (sharp intracellular glass electrodes).
      Confocal imaging was used for visualization of [Ca2+]i events in individual SMCs
      in the arterial wall and membrane currents (patch clamp) measured in individual
      SMCs isolated from the same arteries. A triple peptide combination (37,43Gap 27 +
      40Gap 27 + 43Gap 26) increased intercellular resistance (measured as input
      resistance) in intact arterial segments without affecting the membrane
      conductance of individual cells and also interrupted electrical coupling between
      pairs of rat aortic A7r5 myocytes. In intact arterial segments, the peptides
      desynchronized [Ca2+]i transients in individual SMCs and abolished vasomotion
      without suppressing Ca2+ transients in individual cells. They also depolarized
      SMCs, increased [Ca2+]i, and attenuated acetylcholine-induced, endothelium
      dependent smooth muscle hyperpolarization. Experiments with endothelium-denuded
      arteries suggested that the depolarization produced by the peptides under basal
      conditions was in part secondary to electrical uncoupling of the endothelium from
      SMCs with loss of a tonic hyperpolarizing effect of the endothelium. Taken
      together, the results indicate that connexin-mimetic peptides block electrical
      signaling in rat mesenteric small arteries without exerting major nonjunctional
      effects.

PMID- 16428343
TI  - cAMP signal transduction induces eNOS activation by promoting PKB
      phosphorylation.
AB  - The objective of this study was to determine whether activation of protein kinase
      B (PKB) is involved in the production of nitric oxide (NO) induced by cAMP signal
      transduction. Mongrel dogs were used for this study. Coronary microvessels were
      isolated from the left ventricular free wall of these dog hearts. Forskolin (an
      activator of adenylyl cyclase that increases intracellular cAMP level) and 8
      bromo-cAMP (a membrane-permeable cAMP analog) were used to stimulate NO release
      and activation of PKB and endothelial NO synthase (eNOS) in these blood vessels.
      We found that forskolin and 8-bromo-cAMP increased NO release (quantified by
      using the Griess reaction) from coronary microvessels by 80 +/- 6 and 78 +/- 11
      pmol/mg (mean +/- SE), respectively (P < 0.05 vs. control). Western blot analysis
      showed that forskolin elicited a significant increase in eNOS phosphorylation (59
      +/- 11%) at serine-1177 (a positively regulatory phosphorylation site for eNOS)
      and a significant increase in dephosphorylation (28 +/- 6%) at threonine-495 (a
      negatively regulatory phosphorylation site of eNOS) (P < 0.05 vs. control).
      Interestingly, forskolin also increased the phosphorylation of PKB at serine-473
      (by 49 +/- 17%) and threonine-308 (by 53 +/- 17%), respectively (P < 0.05 vs.
      control; phosphorylation of both sites is required for a full activation of PKB).
      N(omega)-nitro-l-arginine methyl ester (an NOS inhibitor) blocked NO formation,
      Rp diastereomer of cAMP (a PKA inhibitor), and LY-294002 [a PI3-kinase (an
      activator of PKB) inhibitor] prevented the production of NO, phosphorylation of
      PKB, and eNOS induced by forskolin. Our data clearly show an involvement of PKB
      activation in cAMP signal-induced NO production. We are reporting for the first
      time that cAMP signal transduction stimulates eNOS activation through a PKB
      mediated mechanism.

PMID- 16428344
TI  - Increased vascular biosynthesis of tetrahydrobiopterin in apolipoprotein E
      deficient mice.
AB  - Previous studies suggested that loss of tetrahydrobiopterin (BH(4)) may play an
      important role in the pathogenesis of vascular endothelial dysfunction induced by
      diabetes and hypertension. In contrast, controversial results have been reported
      regarding BH(4) metabolism in experimental models of atherosclerosis. Therefore,
      the present study was designed to characterize the expression and activity of GTP
      cyclohydrolase I, a rate-limiting enzyme in biosynthesis of BH(4), during
      atherogenesis. BH(4) levels were significantly increased in atherosclerotic
      aortas of apolipoprotein E (apoE)-deficient mice as compared with wild-type mice
      after 5 mo of Western diet treatment. This increase was further significantly
      enhanced in apoE-deficient mice fed for 9 and 14 mo. Removal of the endothelium
      almost eliminated BH(4) in wild-type mice but not in apoE-deficient mice,
      suggesting that a major component of increased BH(4) synthesis is localized in
      the vascular media of apoE-deficient mice. Oxidative products of BH(4) were low
      and did not differ between wild-type and apoE-deficient mice over the course of
      this study. Increased protein expression and enzymatic activity of GTP
      cyclohydrolase I were detected in aortas of apoE-deficient mice (P < 0.05),
      providing molecular mechanisms responsible for elevation of vascular BH(4). In
      contrast to aortas, we did not detect any change in levels of BH(4) and in GTP
      cyclohydrolase I expression in the brain. Our results demonstrate selective
      increase of intracellular BH(4) levels via elevation of GTP-cyclohydrolase I
      activity in vascular tissue of apoE-deficient mice.

PMID- 16428345
TI  - Arginase: a modulator of myocardial function.

PMID- 16428346
TI  - Defining lipid raft structure and function with proximity imaging.

PMID- 16428347
TI  - Distinct transcriptional regulation of long-chain acyl-CoA synthetase isoforms
      and cytosolic thioesterase 1 in the rodent heart by fatty acids and insulin.
AB  - The molecular mechanism(s) responsible for channeling long-chain fatty acids
      (LCFAs) into oxidative versus nonoxidative pathways is (are) poorly understood in
      the heart. Intracellular LCFAs are converted to long-chain fatty acyl-CoAs (LCFA
      CoAs) by a family of long-chain acyl-CoA synthetases (ACSLs). Cytosolic
      thioesterase 1 (CTE1) hydrolyzes cytosolic LCFA-CoAs to LCFAs, generating a
      potential futile cycle at the expense of ATP utilization. We hypothesized that
      ACSL isoforms and CTE1 are differentially regulated in the heart during
      physiological and pathophysiological conditions. Using quantitative RT-PCR, we
      report that the five known acsl isoforms (acsl1, acsl3, acsl4, acsl5, and acsl6)
      and cte1 are expressed in whole rat and mouse hearts, as well as adult rat
      cardiomyocytes (ARCs). Streptozotocin-induced insulin-dependent diabetes (4 wk)
      and fasting (</=24 h) both dramatically induced cte1 and repressed acsl6 mRNA,
      with no significant effects on the other acsl isoforms. In contrast, high-fat
      feeding (4 wk) induced cte1 without affecting expression of the acsl isoforms in
      the heart. Investigation into the mechanism(s) responsible for these
      transcriptional changes uncovered roles for peroxisome proliferator-activated
      receptor-alpha (PPARalpha) and insulin as regulators of specific acsl isoforms
      and cte1 in the heart. Culturing ARCs with oleate (0.1-0.4 mM) or the PPARalpha
      agonists WY-14643 (1 muM) and fenofibrate (10 muM) consistently induced acsl1 and
      cte1. Conversely, PPARalpha null mouse hearts exhibited decreased acsl1 and cte1
      expression. Culturing ARCs with insulin (10 nM) induced acsl6, whereas specific
      loss of insulin signaling within the heart (cardiac-specific insulin receptor
      knockout mice) caused decreased acsl6 expression. Our data expose differential
      regulation of acsl isoforms and cte1 in the heart, where acsl1 and cte1 are
      PPARalpha-regulated genes, whereas acsl6 is an insulin-regulated gene.

PMID- 16428349
TI  - Single-beat estimation of end-diastolic pressure-volume relationship: a novel
      method with potential for noninvasive application.
AB  - Whereas end-systolic and end-diastolic pressure-volume relations (ESPVR, EDPVR)
      characterize left ventricular (LV) pump properties, clinical utility of these
      relations has been hampered by the need for invasive measurements over a range of
      pressure and volumes. We propose a single-beat approach to estimate the whole
      EDPVR from one measured volume-pressure (Vm and Pm) point. Ex vivo EDPVRs were
      measured from 80 human hearts of different etiologies (normal, congestive heart
      failure, left ventricular assist device support). Independent of etiology, when
      EDPVRs were normalized (EDPVRn) by appropriate scaling of LV volumes, EDPVRns
      were nearly identical and were optimally described by the relation EDP = An.EDV
      (Bn), with An = 28.2 mmHg and Bn = 2.79. V0 (the volume at the pressure of
      approximately 0 mmHg) was predicted by using the relation V0 = Vm.(0.6 -
      0.006.Pm) and V30 by V30 = V0 + (Vm,n - V0)/(Pm/An) (1/Bn). The entire EDPVR of
      an individual heart was then predicted by forcing the curve through Vm, Pm, and
      the predicted V0 and V30. This technique was applied prospectively to the ex vivo
      human EDPVRs not used in determining optimal An and Bn values and to 36 in vivo
      human, 12 acute and 14 chronic canine, and 80 in vivo and ex vivo rat studies.
      The root-mean-square error (RMSE) in pressure between measured and predicted
      EDPVRs over the range of 0-40 mmHg was < 3 mmHg of measured EDPVR in all
      settings, indicating a good predictive value of this approach. Volume-normalized
      EDPVRs have a common shape, despite different etiology and species. This allows
      the entire curve to be predicted by a new method with a potential for noninvasive
      application. The results are most accurate when applied to groups of hearts
      rather than to individual hearts.

PMID- 16428348
TI  - Midbrain vlPAG inhibits rVLM cardiovascular sympathoexcitatory responses during
      electroacupuncture.
AB  - The periaqueductal gray (PAG) is an important integrative region in the
      regulation of autonomic outflow and cardiovascular function and may serve as a
      regulatory center as part of a long-loop pathway during somatic afferent
      stimulation with acupuncture. Because the ventrolateral PAG (vlPAG) provides
      input to the rostral ventrolateral medulla (rVLM), an important area for
      electroacupuncture (EA) regulation of sympathetic outflow, we hypothesized that
      the vlPAG plays a role in the EA-related modulation of rVLM premotor sympathetic
      neurons activated during visceral afferent stimulation and autonomic excitatory
      reflexes. Cats were anesthetized and ventilated, and heart rate and mean blood
      pressure were monitored. Stimulation of the splanchnic nerve by a pledget of
      filter paper soaked in bradykinin (BK, 10 mug/ml) every 10 min on the gallbladder
      induced consistent cardiovascular reflex responses. Bilateral stimulation with EA
      at acupoints over the pericardial meridian (P5-6) situated over the median nerve
      reduced the increases in blood pressure from 34 +/- 3 to 18 +/- 5 mmHg for a
      period of time that lasted for 60 min or more. Unilateral inactivation of
      neuronal activity in the vlPAG with 50-75 nl of kainic acid (KA, 1 mM) restored
      the blood pressure responses from 18 +/- 3 to 36 +/- 5 mmHg during BK-induced
      gallbladder stimulation, an effect that lasted for 30 min. In the absence of EA,
      unilateral microinjection of the excitatory amino acid dl-homocysteic acid (DLH,
      4 nM) in the vlPAG mimicked the effect of EA and reduced the reflex blood
      pressure responses from 35 +/- 6 to 14 +/- 5 mmHg. Responses of 21 cardiovascular
      sympathoexcitatory rVLM neurons, including 12 that were identified as premotor
      neurons, paralleled the cardiovascular responses. Thus splanchnic nerve-evoked
      neuronal discharge of 32 +/- 4 spikes/30 stimuli in six neurons was reduced to 10
      +/- 2 spikes/30 stimuli by EA, which was restored rapidly to 28 +/- 4 spikes/30
      stimuli by unilateral injection of 50 nl KA into the vlPAG. Conversely, 50 nl of
      DLH in the vlPAG reduced the number of action potentials of 5 rVLM neurons from
      30 +/- 4 to 18 +/- 4 spikes/30 stimuli. We conclude that the inhibitory influence
      of EA involves vlPAG stimulation, which, in turn, inhibits rVLM neurons in the EA
      related attenuation of the cardiovascular excitatory response during visceral
      afferent stimulation.

PMID- 16428351
TI  - Activation of cardiac AMP-activated protein kinase by LKB1 expression or chemical
      hypoxia is blunted by increased Akt activity.
AB  - AMP-activated protein kinase (AMPK) plays a major role in the regulation of
      cardiac energy substrate utilization and can be negatively regulated by Akt
      activation in the heart. It has recently been shown that Akt directly
      phosphorylates AMPKalpha(1)/alpha(2) on Ser(485/491) in vitro and prevents the
      AMPK kinase (AMPKK) LKB1 from phosphorylating AMPKalpha at its primary activation
      site, Thr(172) (S Horman, D Vertommen, R Heath, D Neumann, V Mouton, A Woods, U
      Schlattner, T Wallimann, D Carling, L Hue, and MH Rider. J Biol Chem 281: 5335
      5340, 2006). To determine whether this is also the case in the cardiac myocyte,
      neonatal rat cardiac myocytes (NRCM) were infected with a recombinant adenovirus
      expressing a constitutively active mutant of Akt1 (myrAkt1) and then with or
      without adenoviruses expressing the active LKB1 complex. Expression of myrAkt1
      blunted LKB1-induced phosphorylation of AMPKalpha at Thr(172), which resulted in
      a dramatic decrease in phosphorylation of AMPK's target, acetyl CoA-carboxylase.
      This decrease in AMPK activity was associated with prior Akt1-dependent
      phosphorylation of AMPKalpha(1)/alpha(2) at Ser(485/491). To investigate whether
      Akt1 activation was also able to prevent other AMPKKs from phosphorylating
      AMPKalpha, we subjected NRCM to chemical hypoxia and noted a marked increase in
      phosphorylation of AMPKalpha at Thr(172), despite no change in LKB1 activity.
      NRCM expressing myrAkt1 demonstrated increased phosphorylation of
      AMPKalpha(1)/alpha(2) at Ser(485/491) and a complete inhibition of chemical
      hypoxia-induced phosphorylation of AMPKalpha at Thr(172). Taken together, our
      data show that activation of Akt1 is able to prevent activation of cardiac AMPK
      by LKB1 and at least one other AMPKK, likely by prior phosphorylation of
      AMPKalpha(1)/alpha(2) at Ser(485/491).

PMID- 16428350
TI  - Genetic ablation of caveolin-1 modifies Ca2+ spark coupling in murine arterial
      smooth muscle cells.
AB  - L-type, voltage-dependent calcium (Ca(2+)) channels, ryanodine-sensitive Ca(2+)
      release (RyR) channels, and large-conductance Ca(2+)-activated potassium (K(Ca))
      channels comprise a functional unit that regulates smooth muscle contractility.
      Here, we investigated whether genetic ablation of caveolin-1 (cav-1), a caveolae
      protein, alters Ca(2+) spark to K(Ca) channel coupling and Ca(2+) spark
      regulation by voltage-dependent Ca(2+) channels in murine cerebral artery smooth
      muscle cells. Caveolae were abundant in the sarcolemma of control (cav-1(+/+))
      cells but were not observed in cav-1-deficient (cav-1(-/-)) cells. Ca(2+) spark
      and transient K(Ca) current frequency were approximately twofold higher in cav-1(
      /-) than in cav-1(+/+) cells. Although voltage-dependent Ca(2+) current density
      was similar in cav-1(+/+) and cav-1(-/-) cells, diltiazem and Cd(2+), voltage
      dependent Ca(2+) channel blockers, reduced transient K(Ca) current frequency to
      approximately 55% of control in cav-1(+/+) cells but did not alter transient
      K(Ca) current frequency in cav-1(-/-) cells. Furthermore, although K(Ca) channel
      density was elevated in cav-1(-/-) cells, transient K(Ca) current amplitude was
      similar to that in cav-1(+/+) cells. Higher Ca(2+) spark frequency in cav-1(-/-)
      cells was not due to elevated intracellular Ca(2+) concentration, sarcoplasmic
      reticulum Ca(2+) load, or nitric oxide synthase activity. Similarly, Ca(2+) spark
      amplitude and spread, the percentage of Ca(2+) sparks that activated a transient
      K(Ca) current, the amplitude relationship between sparks and transient K(Ca)
      currents, and K(Ca) channel conductance and apparent Ca(2+) sensitivity were
      similar in cav-1(+/+) and cav-1(-/-) cells. In summary, cav-1 ablation elevates
      Ca(2+) spark and transient K(Ca) current frequency, attenuates the coupling
      relationship between voltage-dependent Ca(2+) channels and RyR channels that
      generate Ca(2+) sparks, and elevates K(Ca) channel density but does not alter
      transient K(Ca) current activation by Ca(2+) sparks. These findings indicate that
      cav-1 is required for physiological Ca(2+) spark and transient K(Ca) current
      regulation in cerebral artery smooth muscle cells.

PMID- 16428352
TI  - Compression induced by RV pressure overload decreases regional coronary blood
      flow in anesthetized dogs.
AB  - Pulmonary artery constriction (PAC), a model of right ventricular (RV) pressure
      overload, flattens or inverts the septum and may flatten the left ventricular
      (LV) free wall. Finite element (FE) analysis predicts that such deformations may
      cause substantial compression. This study tests the hypothesis that deformation
      induced myocardial compressive stress impedes coronary blood flow (CBF). Colored
      microspheres ( approximately 2 x 10(6)) were injected into the left atrium of 13
      open-chest, anesthetized dogs under control conditions and during PAC, which
      decreased the end-diastolic transseptal pressure gradient (LV - RV) from 1.6 +/-
      1.3 to -3.4 +/- 1.7 mmHg. Septal and LV deformation was assessed with the use of
      two-dimensional echocardiography, and by FE analysis, the hydrostatic component
      of stress was assessed. Postmortem, a 2.5-cm wide, LV equatorial ring was divided
      into 16 endocardial and epicardial samples. PAC decreased CBF in the FE-predicted
      compression zones, areas with the greatest compression having the greatest
      reductions in CBF. During PAC, compression reached a maximum of 25.3 +/- 1.8 mmHg
      on the (LV) endocardial sides of the RV insertion points, areas that saw CBF
      decrease from 1.05 +/- 0.08 to 0.68 +/- 0.05 ml.min(-1).g(-1) (P < 0.001), more
      than 30%. CBF decreased (from 1.08 +/- 0.07 to 0.81 +/- 0.07 ml.min(-1).g(-1); P
      < 0.001) on the RV side of the midseptum, an area with as much as 16.0 +/- 1.0
      mmHg of compression. Overall, average compressions of 10 mmHg decreased CBF by
      approximately 30%. We conclude that acute RV pressure overload deforms the septum
      and LV and induces compressive stresses that reduce CBF substantially. This may
      help explain why some patients with pulmonary hypertension and no critical
      coronary disease have chest discomfort indistinguishable from angina pectoris.

PMID- 16428353
TI  - Aldosterone increases voltage-gated sodium current in ventricular myocytes.
AB  - The role of aldosterone in the pathogenesis of heart failure (HF) is still poorly
      understood. Recently, aldosterone has been shown to modulate the function of
      cardiac Ca(2+) and K(+) channels, thus playing a role in the electrical
      remodeling process. The goal of this work was to investigate the role of
      aldosterone on the cardiac Na(+) current (I(Na)). We analyzed the effects of
      aldosterone on I(Na) in isolated adult mouse ventricular myocytes, using the
      whole cell patch-clamp technique. After 24 h incubation with 1 microM
      aldosterone, the I(Na) density was significantly increased (+55%), without
      alteration of the biophysical properties and the cell membrane capacitance.
      Aldosterone (10 nM) increased the I(Na) by 23%. In 24-h coincubation experiments,
      with the use of actinomycin D, cycloheximide, or brefeldin A, the effect of
      aldosterone on I(Na) was abolished. Spironolactone (mineralocorticoid receptor
      antagonist, 10 microM) prevented the 1 microM aldosterone-dependent I(Na)
      increase, whereas RU-38486 (glucocorticoid receptor antagonist, 10 microM) did
      not. The action potential duration (APD) was longer in aldosterone-treated
      (APD(90): +53%) than in control myocytes. In addition, the L-type Ca(2+) current
      was also upregulated (+48%). We performed quantitative RT-PCR measurements and
      Western blots to quantify the mRNA and protein levels of Na(v)1.5 and Ca(v)1.2
      (main channels mediating cardiac I(Na) and I(Ca)), but no significant difference
      was found. In conclusion, this study shows that aldosterone upregulates the
      cardiac I(Na) and suggest that this phenomenon may contribute to the HF-induced
      electrical remodeling process that may be reversed by spironolactone.

PMID- 16428354
TI  - Does rural or urban residence make a difference to neonatal outcome in premature
      birth? A regional study in Australia.
AB  - BACKGROUND: Patients living in rural areas may be at a disadvantage in accessing
      tertiary health care. AIM: To test the hypothesis that very premature infants
      born to mothers residing in rural areas have poorer outcomes than those residing
      in urban areas in the state of New South Wales (NSW) and the Australian Capital
      Territory (ACT) despite a coordinated referral and transport system. METHODS:
      "Rural" or "urban" status was based on the location of maternal residence.
      Perinatal characteristics, major morbidity and case mix adjusted mortality were
      compared between 1879 rural and 6775 urban infants <32 weeks gestational age,
      born in 1992-2002 and admitted to all 10 neonatal intensive care units in NSW and
      ACT. RESULTS: Rural mothers were more likely to be teenaged, indigenous, and to
      have had a previous premature birth, prolonged ruptured membrane, and antenatal
      corticosteroid. Urban mothers were more likely to have had assisted conception
      and a caesarean section. More urban (93% v 83%) infants were born in a tertiary
      obstetric hospital. Infants of rural residence had a higher mortality (adjusted
      odds ratio (OR) 1.26, 95% confidence interval (CI) 1.07 to 1.48, p = 0.005). This
      trend was consistently seen in all subgroups and significantly for the tertiary
      hospital born population and the 30-31 weeks gestation subgroup. Regional birth
      data in this gestational age range also showed a higher stillbirth rate among
      rural infants (OR 1.20, 95% CI 1.09 to 1.32, p<0.001). CONCLUSIONS: Premature
      births from rural mothers have a higher risk of stillbirth and mortality in
      neonatal intensive care than urban infants.

PMID- 16428355
TI  - Sucrose and non-nutritive sucking for the relief of pain in screening for
      retinopathy of prematurity: a randomised controlled trial.
AB  - BACKGROUND: Screening is necessary for infants at risk of retinopathy of
      prematurity. Despite local anaesthetic drops, infants find eye examinations
      distressing, displaying behavioural and physiological changes indicating acute
      pain. Oral sucrose and non-nutritive sucking reduce pain responses associated
      with invasive procedures. OBJECTIVE: To evaluate the use of oral sucrose and/or
      pacifier for reducing pain responses during eye examinations. METHODS: Forty
      infants <32 weeks gestation or <1500 g birth weight, in two neonatal units, were
      randomised to one of four interventions administered two minutes before their
      first screening examination: 1 ml sterile water as placebo (group 1, n = 10), 1
      ml 33% sucrose solution (group 2, n = 10), 1 ml sterile water with pacifier
      (group 3, n = 9), or 1 ml 33% sucrose solution with pacifier (group 4, n = 11).
      Examinations were videotaped. Two observers, blind to the intervention, assessed
      recordings. Pain responses were scored using the premature infant pain profile
      (PIPP). RESULTS: The groups were similar in gestation, birth weight, and age at
      examination. Mean PIPP scores were 15.3, 14.3, 12.3, and 12.1 for groups 1, 2, 3,
      and 4 respectively. Analysis of variance showed a significant difference in PIPP
      score between groups (p = 0.023). Infants randomised to pacifiers scored lower
      than those without pacifiers (p = 0.003). There was no difference between groups
      receiving sucrose and those receiving water (p = 0.321). CONCLUSIONS: Non
      nutritive sucking reduced distress responses in infants undergoing screening for
      retinopathy of prematurity. The difference in response was large enough to be
      detected by a validated assessment tool. No synergistic effect of sucrose and
      pacifier was apparent in this group.

PMID- 16428356
TI  - Early postnatal allopurinol does not improve short term outcome after severe
      birth asphyxia.
AB  - OBJECTIVE: To investigate whether postnatal allopurinol would reduce free radical
      induced reperfusion/reoxygenation injury of the brain in severely asphyxiated
      neonates. METHOD: In an interim analysis of a randomised, double blind, placebo
      controlled study, 32 severely asphyxiated infants were given allopurinol or a
      vehicle within four hours of birth. RESULTS: The analysis showed an unaltered
      (high) mortality and morbidity in the infants treated with allopurinol.
      CONCLUSION: Allopurinol treatment started postnatally was too late to reduce the
      early reperfusion induced free radical surge. Allopurinol administration to the
      fetus with (imminent) hypoxia via the mother during labour may be more effective
      in reducing free radical induced post-asphyxial brain damage.

PMID- 16428357
TI  - Effects of exclusive formula or breast milk feeding on oxidative stress in
      healthy preterm infants.
AB  - BACKGROUND: Compared to formula, breast milk is considered to have superior
      antioxidant properties and consequently may reduce the occurrence of a number of
      diseases of prematurity associated with oxidative stress. AIMS: To test whether
      the antioxidant properties of breast milk in healthy premature infants are
      different to those of formula milk by comparing vitamin E levels in milk and
      determining the excretion of malondialdehyde (MDA) in urine. METHODS: Vitamin E
      was measured in the breast milk of 20 mothers who had given birth prematurely.
      Urinary MDA was measured in 10 exclusively breast milk fed and 10 exclusively
      formula fed healthy preterm infants receiving no vitamin supplements. MDA was
      measured after derivatisation with 2,4-dinitrophenylhydrazine and consecutive
      HPLC with UV detection. RESULTS: Urinary MDA concentrations were consistently
      very low (0.074+/-0.033 microM/mM Cr and 0.078+/-0.026 microM/mM Cr in breast and
      formula fed infants respectively) and not significantly different between healthy
      breast milk and formula fed infants. Both breast and formula milk contained
      satisfactory levels (0.3-3.0 mg/100 ml) of vitamin E. CONCLUSION: Antioxidant
      properties of both breast milk and formulae are sufficient to prevent significant
      lipid peroxidation in healthy premature infants.

PMID- 16428358
TI  - A meta-analysis of the effect of high weight on asthma.
AB  - BACKGROUND: Prevalence rates for both overweight and asthma have been increasing
      among children in developed countries over the past two decades. Some recent
      studies have postulated a causal relation between these but have lacked power to
      form a definitive conclusion. AIM: To estimate the effect of high body weight in
      childhood on the future risk of asthma. METHODS: Medline search (1966 to October
      2004), supplemented by manual search of reference lists and grey literature.
      Cohort studies that examined high body weight at birth or during childhood and
      future outcome of asthma were included. Data from each study were extracted on
      exposure status, clinical outcome, and study characteristics. RESULTS: A total of
      402 studies were initially identified, of which 12 met the inclusion criteria.
      The combined results from four studies that examined the effect of high body
      weight during middle childhood on the outcome of subsequent asthma showed a 50%
      increase in relative risk (RR 1.5, 95% CI 1.2 to 1.8). The combined results from
      nine studies that examined the effect of high birth weight on subsequent asthma
      had a pooled RR of 1.2 (95% CI 1.1 to 1.3). There was consistency among the
      results in sensitivity analyses examining studies containing only estimates of
      odds ratios, studies containing only the outcome of physician diagnosis of
      asthma, and studies including all definitions of high body weight. CONCLUSIONS:
      Children with high body weight, either at birth or later in childhood, are at
      increased risk for future asthma. Potential biological mechanisms include diet,
      gastro-oesophageal reflux, mechanical effects of obesity, atopy, and hormonal
      influences. Further research might elucidate the causal pathway, which could
      improve our understanding of the pathophysiology of asthma and perhaps lead to
      knowledge of potential preventive interventions.

PMID- 16428359
TI  - The wisdom of Archimedes.

PMID- 16428360
TI  - Complementary and alternative medicine for children: a good or a bad thing?

PMID- 16428361
TI  - The nursery needs discoveries.

PMID- 16428362
TI  - Sticks and stones can break...: building a case for when names can hurt you.

PMID- 16428364
TI  - Lumbar discitis.

PMID- 16428365
TI  - Survey of paediatric complementary and alternative medicine use in health and
      chronic illness.
AB  - Groups of 25 children with cerebral palsy (CP), inflammatory bowel disease (IBD),
      and cancer were compared to 25 healthy children to establish use of complementary
      or alternative medicine (CAM). Children with chronic disease were greater than
      three times more likely to use CAM, usually without paediatricians' knowledge.

PMID- 16428366
TI  - Do children from an inner city British school meet the recommended levels of
      physical activity? Results from a cross sectional survey using objective
      measurements of physical activity.
AB  - Questionnaire surveys suggest physical activity levels in children are low,
      particularly among children from deprived areas. Using accelerometers, it was
      found that children from a deprived inner city school were active at recommended
      levels and had similar levels of activity to children in other studies from more
      affluent populations. However, this finding was dependent on the threshold used
      to define moderate activity.

PMID- 16428367
TI  - Wide clinical variability among 13 new Cockayne syndrome cases confirmed by
      biochemical assays.
AB  - Cockayne syndrome is a multi-systemic, autosomal recessive disease characterised
      by postnatal growth failure and progressive multi-organ dysfunction. The main
      clinical features are severe dwarfism (<-2 SD), microcephaly (<-3 SD),
      psychomotor delay, sensorial loss (cataracts, pigmentary retinopathy, and
      deafness), and cutaneous photosensitivity. Here, 13 new cases of Cockayne
      syndrome are reported, which have been clinically diagnosed and confirmed using a
      biochemical transcription assay. The wide clinical variability, ranging from
      prenatal features to normal psychomotor development, is emphasised. When cardinal
      features are lacking, the diagnosis of Cockayne syndrome should be considered
      when presented with growth retardation, microcephaly, and one of the suggesting
      features such as enophthalmia, limb ataxia, abnormal auditory evoked responses,
      or increased ventricular size on cerebral imaging.

PMID- 16428368
TI  - The regulation of appetite.
AB  - The worsening global obesity epidemic, particularly the increase in childhood
      obesity, has prompted research into the mechanisms of appetite regulation.
      Complex pathways modulate energy balance, involving appetite centres in the
      hypothalamus and brain stem, and hormonal signals of energy status released by
      the gut and by the periphery. Better understanding of appetite regulation
      improves understanding of the aetiology of obesity. Manipulation of this
      homoeostatic system offers potentially useful treatments for obesity.

PMID- 16428369
TI  - Obesity and the pulmonologist.
AB  - Obese children have more respiratory symptoms than their normal weight peers and
      respiratory related pathology increases with increasing weight. Some will need
      specialist assessment (box 1). Obesity produces mechanical effects on respiratory
      system performance. Breathlessness, wheeze, and cough are not related to
      increased airway responsiveness and may respond more to weight loss than
      bronchodilator therapy. A significant number of obese children have signs and
      symptoms of obstructive sleep apnoea largely related to the effect of obesity on
      upper airway dimensions. It seems likely that unless action is taken soon,
      increasing numbers of children will experience preventable respiratory morbidity
      as a result of nutritional obesity.

PMID- 16428371
TI  - The role of the postgraduate medical education and training board.
AB  - The Postgraduate Medical Education and Training Board (PMETB) is a new
      organisation set up to develop, establish, and maintain standards and
      requirements for postgraduate medical education (PGME) and training. First
      trailed in the NHS Plan, its remit covers the UK. As such it aims to be a single,
      unifying framework for doctors in training.

PMID- 16428370
TI  - Attention deficit hyperactivity disorder: legal and ethical aspects.
AB  - Attention deficit-hyperactivity disorder (ADHD) remains a controversial disorder,
      despite it now being a well validated clinical diagnosis. Ethical and legal
      issues are important in determining how doctors should behave in offering a
      diagnosis or treatment that may generate strong and unpredictable reactions from
      children, their families, or other agencies. A model for routine ethical practice
      was proposed, based on three sets of assumptions. Firstly, that ethical practice
      is consistent with the four principles of beneficence, non-maleficence, justice,
      and respect for autonomy. Secondly, ethical concerns lead to legal processes,
      whose task is to ensure ethical practice. Thirdly, that we are working in the
      interests of our patients. Current relevant literature was organised in terms of
      this model, and recommendations for practice derived from it. Though there is no
      general ethical problem regarding either the routine diagnosis or treatment of
      ADHD, ethical difficulties surround some special cases, especially when doctors
      are working in conjunction with other agencies or coping with non-medical
      frameworks. Particular care needs to be taken with confidentiality and consent,
      the limits of which are currently confused. The model worked well with everyday
      ethical problems, though more difficult cases required careful individual
      scrutiny.

PMID- 16428372
TI  - Out of sight and out of mind? Part I.

PMID- 16428373
TI  - Young people: lost in transition.

PMID- 16428374
TI  - Disseminated sepsis due to a Panton-Valentine leukocidin producing strain of
      community acquired meticillin resistant Staphylococcus aureus and use of
      intravenous immunoglobulin therapy.

PMID- 16428376
TI  - More is not necessarily better.

PMID- 16428378
TI  - Multimedia bullying using a website.

PMID- 16428377
TI  - First, do no harm.

PMID- 16428379
TI  - Understanding retinol metabolism: structure and function of retinol
      dehydrogenases.

PMID- 16428380
TI  - Scanning chromatin: a new paradigm?

PMID- 16428381
TI  - Structural basis for preferential recognition of diaminopimelic acid-type
      peptidoglycan by a subset of peptidoglycan recognition proteins.
AB  - Drosophila peptidoglycan recognition protein (PGRP)-LCx and -LCa are receptors
      that preferentially recognize meso-diaminopimelic acid (DAP)-type peptidoglycan
      (PGN) present in Gram-negative bacteria over lysine-type PGN of gram-positive
      bacteria and initiate the IMD signaling pathway, whereas PGRP-LE plays a
      synergistic role in this process of innate immune defense. How these receptors
      can distinguish the two types of PGN remains unclear. Here the structure of the
      PGRP domain of Drosophila PGRP-LE in complex with tracheal cytotoxin (TCT), the
      monomeric DAP-type PGN, reveals a buried ionic interaction between the unique
      carboxyl group of DAP and a previously unrecognized arginine residue. This
      arginine is conserved in the known DAP-type PGN-interacting PGRPs and contributes
      significantly to the affinity of the protein for the ligand. Unexpectedly, TCT
      induces infinite head-to-tail dimerization of PGRP-LE, in which the disaccharide
      moiety, but not the peptide stem, of TCT is positioned at the dimer interface. A
      sequence comparison suggests that TCT induces heterodimerization of the
      ectodomains of PGRP-LCx and -LCa in a closely analogous manner to prime the IMD
      signaling pathway, except that the heterodimer formation is nonperpetuating.

PMID- 16428382
TI  - Novel permissive role of epidermal growth factor in transforming growth factor
      beta (TGF-beta) signaling and growth suppression. Mediation by stabilization of
      TGF-beta receptor type II.
AB  - Transforming growth factor beta (TGF-beta) signals through TGF-beta receptor
      serine/threonine kinases (TbetaRI and TbetaRII) and Smads, regulating cell growth
      and apoptosis. Although loss of TGF-beta receptor levels is strongly selected for
      during the progression of most cancers, tumor cells frequently escape from
      complete loss of TGF-beta receptors through unknown mechanisms. Here, we provide
      the first evidence that epidermal growth factor (EGF) signaling, which is
      generally enhanced in cancer, is permissive for regulation of gene expression and
      growth suppression by TGF-beta in LNCaP prostate adenocarcinoma cells. Our
      results support that these permissive effects occur through enhanced stability of
      TbetaRII mRNA and reversal of TGF-beta-mediated TbetaRII mRNA loss. Changes in
      stability of TbetaRII mRNA occur soon after EGF or TGF-beta1 addition (optimal
      within 3 h) and are independent of de novo protein synthesis or transcription.
      Remarkably, such loss of TbetaRII by TGF-beta can be mediated by a kinase-dead
      TbetaRII (K277R), as well as by other forms of this receptor harboring mutations
      at prominent autophosphorylation sites. Moreover, Smad3 small interfering RNA,
      which blocks TGF-beta-induced AP-1 promoter activity, does not block changes in
      the expression of TbetaRII by EGF or TGF-beta. We have also shown that changes in
      TbetaRII levels by EGF are EGF receptor-kinase-dependent and are controlled by
      signals downstream of MEK1/2. Our findings provide invaluable insights on the
      role of the EGF receptor-kinase in enhancing TGF-beta responses during prostate
      carcinogenesis.

PMID- 16428383
TI  - Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and
      promotes interleukin-6-induced apoptosis suppression and cell motility.
AB  - Human plasma membrane-associated sialidase (NEU3), specifically hydrolyzing
      gangliosides, plays crucial roles in the regulation of cell surface functions.
      Here we demonstrate that NEU3 mRNA level are increased in renal cell carcinomas
      (RCCs) compared with adjacent non-tumor tissues, significantly correlating with
      elevation of interleukin-6 (IL-6), a pleiotropic cytokine that has been
      implicated in immune responses and pathogenesis of several cancers, including
      RCCs. In human RCC ACHN cells, IL-6 treatment enhanced NEU3 promoter luciferase
      activity 2.5-fold and the endogenous sialidase activity significantly. NEU3
      transfection or IL-6 treatment resulted in both suppression of apoptosis and
      promotion of cell motility, and the combination had synergistic effects. NEU3
      scarcely affected MAPK- or IL-6-induced STAT3 activation but promoted the
      phosphatidylinositol 3-kinase (PI3K)/Akt cascade in both IL-6-dependent and 
      independent ways. Consistent with these data, NEU3 markedly inhibited
      staurosporine-induced caspase-3 activity and enhanced IL-6-dependent inhibition,
      which was abolished by LY294002, a PI3K inhibitor. Furthermore, IL-6 promoted Rho
      activation, and the effect was potentiated by NEU3, leading to increased cell
      motility that was again affected by LY294002. NEU3 silencing by siRNA resulted in
      the opposite: decreased Akt phosphorylation and inhibition of Rho activation.
      Glycolipid analysis showed a decrease in ganglioside GM3 and increase in
      lactosylceramide after NEU3 transfection, with these lipids apparently affecting
      cell apoptosis and motility. The results indicate that NEU3 activated by IL-6
      exerts IL-6-mediated signaling, largely via the PI3K/Akt cascade, in a positive
      feedback manner and contributes to expression of a malignant phenotype in RCCs.
      NEU3 thus may be a useful target for RCC diagnosis and therapy.

PMID- 16428384
TI  - Murine thrombin lacks Na+ activation but retains high catalytic activity.
AB  - Human thrombin utilizes Na+ as a driving force for the cleavage of substrates
      mediating its procoagulant, prothrombotic, and signaling functions. Murine
      thrombin has Asp-222 in the Na+ binding site of the human enzyme replaced by Lys.
      The charge reversal substitution abrogates Na+ activation, which is partially
      restored with the K222D mutation, and ensures high activity even in the absence
      of Na+. This property makes the murine enzyme more resistant to the effect of
      mutations that destabilize Na+ binding and shift thrombin to its anticoagulant
      slow form. Compared with the human enzyme, murine thrombin cleaves fibrinogen and
      protein C with similar k(cat)/K(m) values but activates PAR1 and PAR4 with
      k(cat)/K(m) values 4- and 26-fold higher, respectively. The significantly higher
      specificity constant toward PAR4 accounts for the dominant role of this receptor
      in platelet activation in the mouse. Murine thrombin can also cleave substrates
      carrying Phe at P1, which potentially broadens the repertoire of molecular
      targets available to the enzyme in vivo.

PMID- 16428385
TI  - Evidence for mutagenesis by nitric oxide during nitrate metabolism in Escherichia
      coli.
AB  - In Escherichia coli, nitrosative mutagenesis may occur during nitrate or nitrite
      respiration. The endogenous nitrosating agent N2O3 (dinitrogen trioxide, nitrous
      anhydride) may be formed either by the condensation of nitrous acid or by the
      autooxidation of nitric oxide, both of which are metabolic by-products. The
      purpose of this study was to determine which of these two agents is more
      responsible for endogenous nitrosative mutagenesis. An nfi (endonuclease V)
      mutant was grown anaerobically with nitrate or nitrite, conditions under which it
      has a high frequency of A:T-to-G:C transition mutations because of a defect in
      the repair of hypoxanthine (nitrosatively deaminated adenine) in DNA. These
      mutations could be greatly reduced by two means: (i) introduction of an nirB
      mutation, which affects the inducible cytoplasmic nitrite reductase, the major
      source of nitric oxide during nitrate or nitrite metabolism, or (ii) flushing the
      anaerobic culture with argon (which should purge it of nitric oxide) before it
      was exposed to air. The results suggest that nitrosative mutagenesis occurs
      during a shift from nitrate/nitrite-dependent respiration under hypoxic
      conditions to aerobic respiration, when accumulated nitric oxide reacts with
      oxygen to form endogenous nitrosating agents such as N2O3. In contrast,
      mutagenesis of nongrowing cells by nitrous acid was unaffected by an nirB
      mutation, suggesting that this mutagenesis is mediated by N2O3 that is formed
      directly by the condensation of nitrous acid.

PMID- 16428386
TI  - Regulation and physiologic significance of the agmatine deiminase system of
      Streptococcus mutans UA159.
AB  - We previously demonstrated that Streptococcus mutans expresses a functional
      agmatine deiminase system (AgDS) encoded by the agmatine-inducible aguBDAC operon
      (A. R. Griswold, Y. Y. Chen, and R. A. Burne, J. Bacteriol. 186:1902-1904, 2004).
      The AgDS yields ammonia, CO2, and ATP while converting agmatine to putrescine and
      is proposed to augment the acid resistance properties and pathogenic potential of
      S. mutans. To initiate a study of agu gene regulation, the aguB transcription
      initiation site was identified by primer extension and a putative sigma70-like
      promoter was mapped 5' to aguB. Analysis of the genome database revealed an open
      reading frame (SMU.261c) encoding a putative transcriptional regulator located
      239 bases upstream of aguB. Inactivation of SMU.261c decreased AgD activity by
      sevenfold and eliminated agmatine induction. AgD was also found to be induced by
      certain environmental stresses, including low pH and heat, implying that the AgDS
      may also be a part of a general stress response pathway of this organism.
      Interestingly, an AgDS-deficient strain was unable to grow in the presence of 20
      mM agmatine, suggesting that the AgDS converts a growth-inhibitory substance into
      products that can enhance acid tolerance and contribute to the competitive
      fitness of the organism at low pH. The capacity to detoxify and catabolize
      agmatine is likely to have major ramifications on oral biofilm ecology.

PMID- 16428387
TI  - ohrR and ohr are the primary sensor/regulator and protective genes against
      organic hydroperoxide stress in Agrobacterium tumefaciens.
AB  - The genes involved in organic hydroperoxide protection in Agrobacterium
      tumefaciens were functionally evaluated. Gene inactivation studies and functional
      analyses have identified ohr, encoding a thiol peroxidase, as the gene primarily
      responsible for organic hydroperoxide protection in A. tumefaciens. An ohr mutant
      was sensitive to organic hydroperoxide killing and had a reduced capacity to
      metabolize organic hydroperoxides. ohr is located next to, and is divergently
      transcribed from, ohrR, encoding a sensor and transcription regulator of organic
      hydroperoxide stress. Transcription of both ohr and ohrR was induced by exposure
      to organic hydroperoxides but not by exposure to other oxidants. This induction
      required functional ohrR. The results of gel mobility shift and DNase I
      footprinting assays with purified OhrR, combined with in vivo promoter deletion
      analyses, confirmed that OhrR regulated both ohrR and ohr by binding to a single
      OhrR binding box that overlapped the ohrR and ohr promoters. ohrR and ohr are
      both required for the establishment of a novel cumene hydroperoxide-induced
      adaptive response. Inactivation or overexpression of other Prx family genes
      (prx1, prx2, prx3, bcp1, and bcp2) did not affect either the resistance to, or
      the ability to degrade, organic hydroperoxide. Taken together, the results of
      biochemical, gene regulation and physiological studies support the role of ohrR
      and ohr as the primary system in sensing and protecting A. tumefaciens from
      organic hydroperoxide stress.

PMID- 16428388
TI  - Analysis of the lateral flagellar gene system of Aeromonas hydrophila AH-3.
AB  - Mesophilic Aeromonas strains express a polar flagellum in all culture conditions,
      and certain strains produce lateral flagella on semisolid media or on surfaces.
      Although Aeromonas lateral flagella have been described as a colonization factor,
      little is known about their organization and expression. Here we characterized
      the complete lateral flagellar gene cluster of Aeromonas hydrophila AH-3
      containing 38 genes, 9 of which (lafA-U) have been reported previously. Among the
      flgLL and lafA structural genes we found a modification accessory factor gene
      (maf-5) that is involved in formation of lateral flagella; this is the first time
      that such a gene has been described for lateral flagellar gene systems. All
      Aeromonas lateral flagellar genes were located in a unique chromosomal region, in
      contrast to Vibrio parahaemolyticus, in which the analogous genes are distributed
      in two different chromosomal regions. In A. hydrophila mutations in flhAL, lafK,
      fliJL, flgNL, flgEL, and maf-5 resulted in a loss of lateral flagella and
      reductions in adherence and biofilm formation, but they did not affect polar
      flagellum synthesis. Furthermore, we also cloned and sequenced the A. hydrophila
      AH-3 alternative sigma factor sigma54 (rpoN); mutation of this factor suggested
      that it is involved in expression of both types of flagella.

PMID- 16428389
TI  - Domains required for transcriptional activation show conservation in the mga
      family of virulence gene regulators.
AB  - Mga, or the multigene regulator of the group A streptococcus (GAS) (Streptococcus
      pyogenes), is a transcriptional regulator of virulence genes important for
      colonization and immune evasion. All serotypes of the GAS possess one of two
      divergent mga alleles (mga-1 or mga-2), and orthologues of Mga have also been
      identified in other pathogenic streptococci. To date, the only functional motifs
      established within Mga are two amino-terminal DNA-binding domains (HTH-3 and HTH
      4). To uncover novel domains, a random mutagenesis screen using an M6 Mga (mga-1)
      was undertaken to find mutations leading to a defect in transcriptional
      activation of the Mga-regulated emm gene. In addition to mutations in the
      established DNA-binding domains, the screen also revealed mutations in a region
      conserved among several Mga orthologues. Alanine scanning helped resolve the
      boundaries of this conserved Mga domain (CMD-1) spanning from residues 10 to 15
      of the protein, with the two flanking amino acid residues likely involved in
      protein stability. Transcriptional reporter analyses demonstrated the importance
      of CMD-1 for activation of Pemm and autoactivation of Pmga in the serotype M6
      Mga. Mutational analyses showed that both CMD-1 and HTH-4 are also necessary for
      activation of the promoter target Pmrp in a divergent serotype M4 Mga (mga-2),
      suggesting a conserved functionality. However, in contrast to M6, the M4 Mga
      mutants did not show a defect in autoregulation. Mutation of similar conserved
      residues in the Mga-like regulator DmgB from S. dysgalactiae subsp. dysgalactiae
      showed that CMD-1 and HTH-4 are critical for transcriptional activation in this
      orthologue, implying that a common mechanism of virulence gene activation may
      exist for members of the Mga family of regulators.

PMID- 16428390
TI  - The yjeB (nsrR) gene of Escherichia coli encodes a nitric oxide-sensitive
      transcriptional regulator.
AB  - Microarray studies of the Escherichia coli response to nitric oxide and
      nitrosative stress have suggested that additional transcriptional regulators of
      this response remain to be characterized. We identify here the product of the
      yjeB gene as a negative regulator of the transcription of the ytfE, hmpA and ygbA
      genes, all of which are known to be upregulated by nitrosative stress.
      Transcriptional fusions to the promoters of these genes were expressed
      constitutively in a yjeB mutant, indicating that all three are targets for
      repression by YjeB. An inverted repeat sequence that overlaps the -10 element of
      all three promoters is proposed to be a binding site for the YjeB protein. A
      similar inverted repeat sequence was identified in the tehA promoter, which is
      also known to be sensitive to nitrosative stress. The ytfE, hmpA, ygbA, and tehA
      promoters all caused derepression of a ytfE-lacZ transcriptional fusion when
      present in the cell in multiple copies, presumably by a repressor titration
      effect, suggesting the presence of functional YjeB binding sites in these
      promoters. However, YjeB regulation of tehA was weak, as judged by the activity
      of a tehA-lacZ fusion, perhaps because YjeB repression of tehA is masked by other
      regulatory mechanisms. Promoters regulated by YjeB could be derepressed by iron
      limitation, which is consistent with an iron requirement for YjeB activity. The
      YjeB protein is a member of the Rrf2 family of transcriptional repressors and
      shares three conserved cysteine residues with its closest relatives. We propose a
      regulatory model in which the YjeB repressor is directly sensitive to nitrosative
      stress. On the basis of similarity to the nitrite-responsive repressor NsrR from
      Nitrosomonas europaea, we propose that the yjeB gene of E. coli be renamed nsrR.

PMID- 16428392
TI  - Topology and boundaries of the aerotaxis receptor Aer in the membrane of
      Escherichia coli.
AB  - Escherichia coli chemoreceptors are type I membrane receptors that have a
      periplasmic sensing domain, a cytosolic signaling domain, and two transmembrane
      segments. The aerotaxis receptor, Aer, is different in that both its sensing and
      signaling regions are proposed to be cytosolic. This receptor has a 38-residue
      hydrophobic segment that is thought to form a membrane anchor. Most transmembrane
      prediction programs predict a single transmembrane-spanning segment, but such a
      topology is inconsistent with recent studies indicating that there is direct
      communication between the membrane flanking PAS and HAMP domains. We studied the
      overall topology and membrane boundaries of the Aer membrane anchor by a cysteine
      scanning approach. The proximity of 48 cognate cysteine replacements in Aer
      dimers was determined in vivo by measuring the rate and extent of disulfide cross
      linking after adding the oxidant copper phenanthroline, both at room temperature
      and to decrease lateral diffusion in the membrane, at 4 degrees C. Membrane
      boundaries were identified in membrane vesicles using 5-iodoacetamidofluorescein
      and methoxy polyethylene glycol 5000 (mPEG). To map periplasmic residues,
      accessible cysteines were blocked in whole cells by pretreatment with 4-acetamido
      4'-maleimidylstilbene-2, 2' disulfonic acid before the cells were lysed in the
      presence of mPEG. The data were consistent with two membrane-spanning segments,
      separated by a short periplasmic loop. Although the membrane anchor contains a
      central proline residue that reaches the periplasm, its position was permissive
      to several amino acid and peptide replacements.

PMID- 16428391
TI  - Functional and topological characterization of novel components of the comB DNA
      transformation competence system in Helicobacter pylori.
AB  - Helicobacter pylori is one of the most diverse bacterial species known. A
      rational basis for this genetic variation may be provided by its natural
      competence for genetic transformation and high-frequency recombination. Many
      bacterial competence systems have homology with proteins that are involved in the
      assembly of type IV pili and type II secretion systems. In H. pylori, DNA uptake
      relies on a transport system related to type IV secretion systems (T4SS)
      designated the comB system. The prototype of a T4SS in Agrobacterium tumefaciens
      consists of 11 VirB proteins and VirD4, which form the core unit necessary for
      the delivery of single proteins or large nucleoprotein complexes into target
      cells. In the past we identified proteins ComB4 and ComB7 through ComB10 as being
      involved in the process of DNA uptake in H. pylori. In this study we identified
      and functionally characterized further (T4SS-homologous) components of the comB
      transformation competence system. By combining computer prediction modeling,
      experimental topology determination, generation of knockout strains, and genetic
      complementation studies we identified ComB2, ComB3, and ComB6 as essential
      components of the transformation apparatus, structurally and functionally
      homologous to VirB2, VirB3, and VirB6, respectively. comB2, comB3, and comB4 are
      organized as a separate operon. Thus, for the H. pylori comB system, all T4SS
      core components have been identified except for homologues to VirB1, VirD4,
      VirB5, and VirB11.

PMID- 16428394
TI  - Function and evolution of plasmid-borne genes for pyrimidine biosynthesis in
      Borrelia spp.
AB  - The thyX gene for thymidylate synthase of the Lyme borreliosis (LB) agent
      Borrelia burgdorferi is located in a 54-kb linear plasmid. In the present study,
      we identified an orthologous thymidylate synthase gene in the relapsing fever
      (RF) agent Borrelia hermsii, located it in a 180-kb linear plasmid, and
      demonstrated its expression. The functions of the B. hermsii and B. burgdorferi
      thyX gene products were evaluated both in vivo, by complementation of a
      thymidylate synthase-deficient Escherichia coli mutant, and in vitro, by testing
      their activities after purification. The B. hermsii thyX gene complemented the
      thyA mutation in E. coli, and purified B. hermsii ThyX protein catalyzed the
      conversion of dTMP from dUMP. In contrast, the B. burgdorferi ThyX protein had
      only weakly detectable activity in vitro, and the B. burgdorferi thyX gene did
      not provide complementation in vivo. The lack of activity of B. burgdorferi's
      ThyX protein was associated with the substitution of a cysteine for a highly
      conserved arginine at position 91. The B. hermsii thyX locus was further
      distinguished by the downstream presence in the plasmid of orthologues of nrdI,
      nrdE, and nrdF, which encode the subunits of ribonucleoside diphosphate reductase
      and which are not present in the LB agents B. burgdorferi and Borrelia garinii.
      Phylogenetic analysis suggested that the nrdIEF cluster of B. hermsii was
      acquired by horizontal gene transfer. These findings indicate that Borrelia spp.
      causing RF have a greater capability for de novo pyrimidine synthesis than those
      causing LB, thus providing a basis for some of the biological differences between
      the two groups of pathogens.

PMID- 16428393
TI  - Peptidoglycan O acetylation and autolysin profile of Enterococcus faecalis in the
      viable but nonculturable state.
AB  - The O acetylation of peptidoglycan occurs specifically at the C-6 hydroxyl group
      of muramoyl residues. Using a combination of high-performance liquid
      chromatography-based organic acid analysis and carbohydrate analysis by high-pH
      anion-exchange chromatography, we determined that strains of Entercoccus durans,
      E. faecalis, E. faecium, and E. hirae produce O-acetylated peptidoglycan. The
      levels of O acetylation ranged from 19% to 72% relative to the muramic acid
      content, and they were found to vary with the growth phase of the culture.
      Increases of 10 to 40% in O acetylation were observed with cultures entering the
      stationary phase. Cells of E. faecalis in the viable but nonculturable (VBNC)
      state had the highest levels of peptidoglycan O acetylation. The presence of this
      modification to peptidoglycan was shown to inhibit the action of hen egg white
      lysozyme in a concentration-dependent manner. Zymography using sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis gels containing either O-acetylated or
      chemically de-O-acetylated peptidoglycan was used to monitor the production of
      specific autolysins in E. faecalis. Differences in the expression of specific
      autolysins were observed with the age of the culture, and VBNC E. faecalis
      produced the highest levels of these enzymes. This technique also permitted
      classification of the enterococcal autolysins into enzymes that preferentially
      hydrolyze either O-acetylated or non-O-acetylated peptidoglycan and enzymes that
      show no apparent preference for either substrate type.

PMID- 16428395
TI  - Arginine-dependent gene regulation via the ArgR repressor is species specific in
      chlamydia.
AB  - Some, but not all, Chlamydia spp. are predicted to encode a homolog of ArgR, a
      master regulatory molecule that modulates arginine biosynthesis and catabolism in
      bacteria in response to intracellular arginine levels. While genes for arginine
      biosynthesis are apparently missing in Chlamydia, a putative arginine transport
      system encoded by glnP, glnQ, and artJ is present. We found that recombinant
      Chlamydia pneumoniae ArgR functions as an arginine-dependent aporepressor that
      bound specifically to operator sequences upstream of the glnPQ operon. ArgR was
      able to repress transcription in a promoter-specific manner that was dependent on
      the concentration of the corepressor l-arginine. We were able to locate ArgR
      operators upstream of glnPQ in C. pneumoniae and Chlamydophila caviae but not
      Chlamydia trachomatis, which corresponded to the predicted presence or absence of
      ArgR in these chlamydial species. Our findings indicate that only some members of
      the family Chlamydiaceae have an arginine-responsive mechanism of gene regulation
      that is predicted to control arginine uptake from the host cell. This is the
      first study to directly demonstrate a species-specific mechanism of
      transcriptional regulation in Chlamydia.

PMID- 16428396
TI  - Polyamine-mediated resistance of uropathogenic Escherichia coli to nitrosative
      stress.
AB  - During the course of a urinary tract infection, substantial levels of nitric
      oxide and reactive nitrogen intermediates are generated. We have found that many
      uropathogenic strains of Escherichia coli display far greater resistance to
      nitrosative stress than the K-12 reference strain MG1655. By selecting and
      screening for uropathogenic E. coli transposon mutants that are unable to grow in
      the presence of acidified nitrite, the cadC gene product was identified as a key
      facilitator of nitrosative stress resistance. Mutation of cadC, or its
      transcriptional targets cadA and cadB, results in loss of significant production
      of the polyamine cadaverine and increased sensitivity to acidified nitrite.
      Exogenous addition of cadaverine or other polyamines rescues growth of cad
      mutants under nitrosative stress. In wild-type cells, the concentration of
      cadaverine produced per cell is substantially increased by exposure to acidified
      nitrite. The mechanism behind polyamine-mediated rescue from nitrosative stress
      is unclear, but it is not attributable solely to chemical quenching of reactive
      nitrogen species or reduction in mutation frequency.

PMID- 16428397
TI  - Effect of nitrogen source on cyanophycin synthesis in Synechocystis sp. strain
      PCC 6308.
AB  - Experiments were carried out to examine the effects of nitrogen source on
      nitrogen incorporation into cyanophycin during nitrogen limitation and repletion,
      both with or without inhibition of protein synthesis, in cyanobacteria grown on
      either nitrate or ammonium. The use of nitrate and ammonium, 14N labeled in the
      growth medium and 15N labeled in the repletion medium, allows the determination
      of the source of nitrogen in cyanophycin using proton nuclear magnetic resonance
      spectroscopy. The data suggest that nitrogen from both the breakdown of cellular
      protein (14N) and directly from the medium (15N) is incorporated into
      cyanophycin. Nitrogen is incorporated into cyanophycin at different rates and to
      different extents, depending on the source of nitrogen (ammonium or nitrate) and
      whether the cells are first starved for nitrogen. These differences appear to be
      related to the activity of nitrate reductase in cells and to the possible
      expression of cyanophycin synthetase during nitrogen starvation.

PMID- 16428398
TI  - Characterization of cis-acting sites controlling arginine deiminase gene
      expression in Streptococcus gordonii.
AB  - The arginine deiminase system (ADS) is responsible for the production of
      ornithine, CO2, ammonia, and ATP from arginine. The ADS of the oral bacterium
      Streptococcus gordonii plays major roles in physiologic homeostasis, acid
      tolerance, and oral biofilm ecology. To further our understanding of the
      transcriptional regulation of the ADS (arc) operon, the binding of the ArcR
      transcriptional activator, which governs expression of the ADS in response to
      arginine, was investigated by DNase I protection and gel mobility shift assays.
      An ArcR binding sequence was found that was 27 bp in length and had little
      sequence similarity to binding sites of other arginine metabolism regulators. The
      presence of arginine at physiologically relevant concentrations enhanced the
      binding of ArcR to its target. Using cat fusions, various deletion and
      substitution mutations within the putative ArcR footprint were shown to cause
      dramatic reductions in expression from the arcA promoter in vivo, confirming that
      the 27-bp sequence is required for optimal expression and induction of the ADS by
      arginine. Mutation of two putative catabolite response elements (CREs) within the
      arc promoter region showed that both CREs contribute to catabolite repression. A
      thorough understanding of the regulation of the ADS in S. gordonii and related
      organisms is needed to develop ways to exploit arginine catabolism for the
      control of oral diseases. Identification of the ArcR and CcpA binding sites lays
      the foundation for a more complete understanding of the complex interactions of
      multiple regulatory proteins with elements in the arc promoter region.

PMID- 16428399
TI  - Two DNA invertases contribute to flagellar phase variation in Salmonella enterica
      serovar Typhimurium strain LT2.
AB  - Salmonella enterica serovar Typhimurium strain LT2 possesses two nonallelic
      structural genes, fliC and fljB, for flagellin, the component protein of
      flagellar filaments. Flagellar phase variation occurs by alternative expression
      of these two genes. This is controlled by the inversion of a DNA segment, called
      the H segment, containing the fljB promoter. H inversion occurs by site-specific
      recombination between inverted repetitious sequences flanking the H segment. This
      recombination has been shown in vivo and in vitro to be mediated by a DNA
      invertase, Hin, whose gene is located within the H segment. However, a search of
      the complete genomic sequence revealed that LT2 possesses another DNA invertase
      gene that is located adjacent to another invertible DNA segment within a resident
      prophage, Fels-2. Here, we named this gene fin. We constructed hin and fin
      disruption mutants from LT2 and examined their phase variation abilities. The hin
      disruption mutant could still undergo flagellar phase variation, indicating that
      Hin is not the sole DNA invertase responsible for phase variation. Although the
      fin disruption mutant could undergo phase variation, fin hin double mutants could
      not. These results clearly indicate that both Hin and Fin contribute to flagellar
      phase variation in LT2. We further showed that a phase-stable serovar, serovar
      Abortusequi, which is known to possess a naturally occurring hin mutation, lacks
      Fels-2, which ensures the phase stability in this serovar.

PMID- 16428400
TI  - FljA-mediated posttranscriptional control of phase 1 flagellin expression in
      flagellar phase variation of Salmonella enterica serovar Typhimurium.
AB  - Flagellar phase variation of Salmonella is a phenomenon where two flagellin
      genes, fliC (phase 1) and fljB (phase 2), are expressed alternately. This is
      controlled by the inversion of a DNA segment containing the promoter for the fljB
      gene. The fljB gene constitutes an operon with the fljA gene, which encodes a
      negative regulator for fliC expression. Previous biochemical analysis suggested
      that phase variation might depend on alternative synthesis of phase-specific
      flagellin mRNA (H. Suzuki and T. Iino, J. Mol. Biol. 81:57-70, 1973). However,
      recently reported results suggested that FljA-dependent inhibition might be
      mediated by a posttranscriptional control mechanism (H. R. Bonifield and K. T.
      Hughes, J. Bacteriol. 185:3567-3574, 2003). In this study, we reexamined the
      mechanism of FljA-mediated inhibition of fliC expression more carefully. Northern
      blotting analysis revealed that no fliC mRNA was detected in phase 2 cells.
      However, only a moderate decrease in beta-galactosidase activity was observed
      from the fliC-lacZ transcriptional fusion gene in phase 2 cells compared with
      that in phase 1 cells. In contrast, the expression of the fliC-lacZ translational
      fusion gene was severely impaired in phase 2 cells. The half-life of fliC mRNA
      was shown to be much shorter in phase 2 cells than in phase 1 cells. Purified His
      tagged FljA protein was shown to bind specifically to fliC mRNA and inhibit the
      translation from fliC mRNA in vitro. On the basis of these results, we propose
      that in phase 2 cells, FljA binds to fliC mRNA and inhibits its translation,
      which in turn facilitates its degradation.

PMID- 16428401
TI  - GTPase activity, structure, and mechanical properties of filaments assembled from
      bacterial cytoskeleton protein MreB.
AB  - MreB, a major component of the recently discovered bacterial cytoskeleton,
      displays a structure homologous to its eukaryotic counterpart actin. Here, we
      study the assembly and mechanical properties of Thermotoga maritima MreB in the
      presence of different nucleotides in vitro. We found that GTP, not ADP or GDP,
      can mediate MreB assembly into filamentous structures as effectively as ATP. Upon
      MreB assembly, both GTP and ATP release the gamma phosphate at similar rates.
      Therefore, MreB is an equally effective ATPase and GTPase. Electron microscopy
      and quantitative rheology suggest that the morphologies and micromechanical
      properties of filamentous ATP-MreB and GTP-MreB are similar. In contrast,
      mammalian actin assembly is favored in the presence of ATP over GTP. These
      results indicate that, despite high structural homology of their monomers, T.
      maritima MreB and actin filaments display different assembly, morphology,
      micromechanics, and nucleotide-binding specificity. Furthermore, the biophysical
      properties of T. maritima MreB filaments, including high rigidity and propensity
      to form bundles, suggest a mechanism by which MreB helical structure may be
      involved in imposing a cylindrical architecture on rod-shaped bacterial cells.

PMID- 16428402
TI  - A selC-associated genomic island of the extraintestinal avian pathogenic
      Escherichia coli strain BEN2908 is involved in carbohydrate uptake and virulence.
AB  - The complete nucleotide sequence and genetic organization of a new genomic island
      (AGI-3) isolated from the extraintestinal avian pathogenic Escherichia coli
      strain BEN2908 is reported. This 49,600-bp island is inserted at the selC locus
      and contains putative mobile genetic elements such as a phage-related integrase
      gene, transposase genes, and direct repeats. AGI-3 shows a mosaic structure of
      five modules. Some of these modules are present in other E. coli strains and in
      other pathogenic bacterial species. The gene cluster aec-35 to aec-37 of module 1
      encodes proteins associated with carbohydrates assimilation such as a major
      facilitator superfamily transporter (Aec-36), a glycosidase (Aec-37), and a
      putative transcriptional regulator of the LacI family (Aec-35). The aec-35 to aec
      37 cluster was found in 11.6% of the tested pathogenic and nonpathogenic E. coli
      strains. When present, the aec-35 to aec-37 cluster is strongly associated with
      the selC locus (97%). Deletion of the aec-35-aec-37 region affects the
      assimilation of seven carbohydrates, decreases the growth rate of the strain in
      minimal medium containing galacturonate or trehalose, and attenuates the
      virulence of E. coli BEN2908 for chickens.

PMID- 16428403
TI  - Regulation of the glucosyltransferase (gtfBC) operon by CovR in Streptococcus
      mutans.
AB  - Streptococcus mutans is an important etiological agent of dental caries in
      humans. The extracellular polysaccharides synthesized by cell-associated
      glucosyltransferases (encoded by gtfBC) from sucrose have been recognized as one
      of the important virulence factors that promote cell aggregation and adherence to
      teeth, leading to dental plaque formation. In this study, we have characterized
      the effect of CovR, a global response regulator, on glucosyltransferase
      expression. Inactivation of covR in strain UA159 resulted in a marked increase in
      the GtfB and GtfC proteins, as analyzed by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. With the use of a transcriptional reporter system of a
      single chromosomal copy of the PgtfB-gusA and PgtfC-gusA fusions, we confirmed
      the transcriptional regulation of these promoters by CovR. By in vitro
      electrophoretic mobility shift assays with purified CovR protein, we showed that
      CovR regulates these promoters directly. DNase I footprinting analyses suggest
      that CovR binds to large regions on these promoters near the transcription start
      sites. Taken together, our results indicate that CovR negatively regulates the
      expression of the gtfB and gtfC genes by directly binding to the promoter region.

PMID- 16428404
TI  - Anatomy of the replication origin of plasmid ColE2-P9.
AB  - The plasmid ColE2-P9 origin is a 32-bp region which is specifically recognized by
      the plasmid-specified Rep protein to initiate DNA replication. We analyzed the
      structural and functional organization of the ColE2 origin by using various
      derivatives carrying deletions and single-base-pair substitutions. The origin may
      be divided into three subregions: subregion I, which is important for stable
      binding of the Rep protein; subregion II, which is important for binding of the
      Rep protein and for initiation of DNA replication; and subregion III, which is
      important for DNA replication but apparently not for binding of the Rep protein.
      The Rep protein might recognize three specific DNA elements in subregions I and
      II. The relative transformation frequency of the autonomously replicating
      plasmids carrying deletions in subregion I is lower, and nevertheless the copy
      numbers of these plasmids in host bacteria are higher than those of the wild-type
      plasmid. Efficient and stable binding of the Rep protein to the origin might be
      important for the replication efficiency to be at the normal (low) level.
      Subregion II might be essential for interaction with the catalytic domain of the
      Rep protein for primer RNA synthesis. The 8-bp sequence across the border of
      subregions II and III, including the primer sequence, is conserved in the
      (putative) origins of many plasmids, the putative Rep proteins of which are
      related to the ColE2-P9 Rep protein. Subregion III might be required for a step
      that is necessary after Rep protein binding has taken place.

PMID- 16428405
TI  - Native cell wall organization shown by cryo-electron microscopy confirms the
      existence of a periplasmic space in Staphylococcus aureus.
AB  - The current perception of the ultrastructure of gram-positive cell envelopes
      relies mainly on electron microscopy of thin sections and on sample preparation.
      Freezing of cells into a matrix of amorphous ice (i.e., vitrification) results in
      optimal specimen preservation and allows the observation of cell envelope
      boundary layers in their (frozen) hydrated state. In this report, cryo
      transmission electron microscopy of frozen-hydrated sections of Staphylococcus
      aureus D2C was used to examine cell envelope organization. A bipartite wall was
      positioned above the plasma membrane and consisted of a 16-nm low-density inner
      wall zone (IWZ), followed by a 19-nm high-density outer wall zone (OWZ).
      Observation of plasmolyzed cells, which were used to artificially separate the
      membrane from the wall, showed membrane vesicles within the space associated with
      the IWZ in native cells and a large gap between the membrane and OWZ, suggesting
      that the IWZ was devoid of a cross-linked polymeric cell wall network. Isolated
      wall fragments possessed only one zone of high density, with a constant level of
      density throughout their thickness, as was previously seen with the OWZs of
      intact cells. These results strongly indicate that the IWZ represents a
      periplasmic space, composed mostly of soluble low-density constituents confined
      between the plasma membrane and OWZ, and that the OWZ represents the
      peptidoglycan-teichoic acid cell wall network with its associated proteins. Cell
      wall differentiation was also seen at the septum of dividing cells. Here, two
      high-density zones were sandwiched between three low-density zones. It appeared
      that the septum consisted of an extension of the IWZ and OWZ from the outside
      peripheral wall, plus a low-density middle zone that separated adjacent septal
      cross walls, which could contribute to cell separation during division.

PMID- 16428406
TI  - Characterization of the biosynthetic pathway of glucosylglycerate in the archaeon
      Methanococcoides burtonii.
AB  - The pathway for the synthesis of the organic solute glucosylglycerate (GG) is
      proposed based on the activities of the recombinant glucosyl-3-phosphoglycerate
      synthase (GpgS) and glucosyl-3-phosphoglycerate phosphatase (GpgP) from
      Methanococcoides burtonii. A mannosyl-3-phosphoglycerate phosphatase gene
      homologue (mpgP) was found in the genome of M. burtonii (http://www.jgi.doe.gov),
      but an mpgS gene coding for mannosyl-3-phosphoglycerate synthase (MpgS) was
      absent. The gene upstream of the mpgP homologue encoded a putative
      glucosyltransferase that was expressed in Escherichia coli. The recombinant
      product had GpgS activity, catalyzing the synthesis of glucosyl-3
      phosphoglycerate (GPG) from GDP-glucose and d-3-phosphoglycerate, with a high
      substrate specificity. The recombinant MpgP protein dephosphorylated GPG to GG
      and was also able to dephosphorylate mannosyl-3-phosphoglycerate (MPG) but no
      other substrate tested. Similar flexibilities in substrate specificity were
      confirmed in vitro for the MpgPs from Thermus thermophilus, Pyrococcus
      horikoshii, and "Dehalococcoides ethenogenes." GpgS had maximal activity at 50
      degrees C. The maximal activity of GpgP was at 50 degrees C with GPG as the
      substrate and at 60 degrees C with MPG. Despite the similarity of the sugar
      donors GDP-glucose and GDP-mannose, the enzymes for the synthesis of GPG or MPG
      share no amino acid sequence identity, save for short motifs. However, the
      hydrolysis of GPG and MPG is carried out by phosphatases encoded by homologous
      genes and capable of using both substrates. To our knowledge, this is the first
      report of the elucidation of a biosynthetic pathway for glucosylglycerate.

PMID- 16428407
TI  - Distribution and genetic diversity of the ABC transporter lipoproteins PiuA and
      PiaA within Streptococcus pneumoniae and related streptococci.
AB  - Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide.
      The existence of approximately 90 antigenically distinct capsular serotypes has
      greatly complicated the development of an effective pneumococcal vaccine.
      Virulence-associated proteins common and conserved among all capsular types now
      represent the best strategy to combat pneumococcal infections. PiuA and PiaA are
      the lipoprotein components of two pneumococcal iron ABC transporters and are
      required for full virulence in mouse models of infection. Here we describe a
      study of the distribution and genetic diversity of PiuA and PiaA within typical
      and atypical S. pneumoniae, Streptococcus oralis, and Streptococcus mitis
      strains. The genes encoding both PiuA and PiaA were present in all typical
      pneumococci tested, (covering 20 and 27 serotypes, respectively). The piuA gene
      was highly conserved within the typical pneumococci (0.3% nucleotide divergence),
      but was also present in "atypical" pneumococci and the closely related species S.
      mitis and S. oralis, showing up to 10.4% nucleotide divergence and 7.5% amino
      acid divergence from the typical pneumococcal alleles. Conversely, the piaA gene
      was found to be specific to typical pneumococci, 100% conserved, and absent from
      the oral streptococci, including isolates of S. mitis known to possess
      pneumolysin and autolysin. These are desirable qualities for a vaccine candidate
      and as a diagnostic tool for S. pneumoniae.

PMID- 16428408
TI  - Biochemical analysis of Lpt3, a protein responsible for phosphoethanolamine
      addition to lipooligosaccharide of pathogenic Neisseria.
AB  - The inner core of neisserial lipooligosaccharide (LOS) contains heptose residues
      that can be decorated by phosphoethanolamine (PEA). PEA modification of heptose
      II (HepII) can occur at the 3, 6, or 7 position(s). We used a genomic DNA
      sequence of lpt3, derived from Neisseria meningitidis MC58, to search the genomic
      sequence of N. gonorrhoeae FA1090 and identified a homolog of lpt3 in N.
      gonorrhoeae. A PCR amplicon containing lpt3 was amplified from F62DeltaLgtA,
      cloned, mutagenized, and inserted into the chromosome of N. gonorrhoeae strain
      F62DeltaLgtA, producing strain F62DeltaLgtAlpt3::Tn5. LOS isolated from this
      strain lost the ability to bind monoclonal antibody (MAb) 2-1-L8. Complementation
      of this mutation by genetic removal of the transposon insertion restored MAb 2-1
      L8 binding. Mass spectrometry analysis of LOS isolated from the F62DeltaLgtA
      indicated that this strain contained two PEA modifications on its LOS.
      F62DeltaLgtAlpt3::Tn5 lacked a PEA modification on its LOS, a finding consistent
      with the hypothesis that lpt3 encodes a protein mediating PEA addition onto
      gonococcal LOS. The DNA encoding lpt3 was cloned into an expression vector and
      Lpt3 was purified. Purified Lpt3 was able to mediate the addition of PEA to LOS
      isolated from F62DeltaLgtAlpt3::Tn5.

PMID- 16428409
TI  - Identification and characterization of RbmA, a novel protein required for the
      development of rugose colony morphology and biofilm structure in Vibrio cholerae.
AB  - Phase variation between smooth and rugose colony variants of Vibrio cholerae is
      predicted to be important for the pathogen's survival in its natural aquatic
      ecosystems. The rugose variant forms corrugated colonies, exhibits increased
      levels of resistance to osmotic, acid, and oxidative stresses, and has an
      enhanced capacity to form biofilms. Many of these phenotypes are mediated in part
      by increased production of an exopolysaccharide termed VPS. In this study, we
      compared total protein profiles of the smooth and rugose variants using two
      dimensional gel electrophoresis and identified one protein that is present at a
      higher level in the rugose variant. A mutation in the gene encoding this protein,
      which does not have any known homologs in the protein databases, causes cells to
      form biofilms that are more fragile and sensitive to sodium dodecyl sulfate than
      wild-type biofilms. The results indicate that the gene, termed rbmA (rugosity and
      biofilm structure modulator A), is required for rugose colony formation and
      biofilm structure integrity in V. cholerae. Transcription of rbmA is positively
      regulated by the response regulator VpsR but not VpsT.

PMID- 16428410
TI  - Segregation of the replication terminus of the two Vibrio cholerae chromosomes.
AB  - Genome duplication and segregation normally are completed before cell division in
      all organisms. The temporal relation of duplication and segregation, however, can
      vary in bacteria. Chromosomal regions can segregate towards opposite poles as
      they are replicated or can stay cohered for a considerable period before
      segregation. The bacterium Vibrio cholerae has two differently sized circular
      chromosomes, chromosome I (chrI) and chrII, of about 3 and 1 Mbp, respectively.
      The two chromosomes initiate replication synchronously, and the shorter chrII is
      expected to complete replication earlier than the longer chrI. A question arises
      as to whether the segregation of chrII also is completed before that of chrI. We
      fluorescently labeled the terminus regions of chrI and chrII and followed their
      movements during the bacterial cell cycle. The chrI terminus behaved similarly to
      that of the Escherichia coli chromosome in that it segregated at the very end of
      the cell division cycle: cells showed a single fluorescent focus even when the
      division septum was nearly complete. In contrast, the single focus representing
      the chrII terminus could divide at the midcell position well before cell
      septation was conspicuous. There were also cells where the single focus for chrII
      lingered at midcell until the end of a division cycle, like the terminus of chrI.
      The single focus in these cells overlapped with the terminus focus for chrI in
      all cases. It appears that there could be coordination between the two
      chromosomes through the replication and/or segregation of the terminus region to
      ensure their segregation to daughter cells.

PMID- 16428411
TI  - Bacillus anthracis IsdG, a heme-degrading monooxygenase.
AB  - Bacillus anthracis, the causative agent of anthrax, utilizes hemin and hemoglobin
      for growth in culture, suggesting that these host molecules serve as sources for
      the nutrient iron during bacterial infection. Bioinformatic analyses of the B.
      anthracis genome revealed genes with similarity to the iron-regulated surface
      determinant (isd) system responsible for heme uptake in Staphylococcus aureus. We
      show that the protein product of one of these genes, isdG, binds hemin in a
      manner resembling the heme binding of known heme oxygenases. Formation of
      IsdG:hemin complexes in the presence of a suitable electron donor, e.g.,
      ascorbate or cytochrome P450 reductase, promotes catalytic degradation of hemin
      to biliverdin with concomitant release of iron. IsdG is required for B. anthracis
      utilization of hemin as a sole iron source, and it is also necessary for
      bacterial protection against heme-mediated toxicity. These data suggest that IsdG
      functions as a heme-degrading monooxygenase in B. anthracis.

PMID- 16428412
TI  - Complex regulation of arsenite oxidation in Agrobacterium tumefaciens.
AB  - Seminal regulatory controls of microbial arsenite [As(III)] oxidation are
      described in this study. Transposon mutagenesis of Agrobacterium tumefaciens
      identified genes essential for As(III) oxidation, including those coding for a
      two-component signal transduction pair. The transposon interrupted a response
      regulator gene (referred to as aoxR), which encodes an ntrC-like protein and is
      immediately downstream of a gene (aoxS) encoding a protein with primary
      structural features found in sensor histidine kinases. The structural genes for
      As(III) oxidase (aoxAB), a c-type cytochrome (cytc2and molybdopterin biosynthesis
      (chlE) were downstream of aoxR. The mutant could not be complemented by aoxSR in
      trans but was complemented by a clone containing aoxS-aoxR-aoxA-aoxB-cytc2 and
      consistent with reverse transcriptase (RT) PCR experiments, which demonstrated
      these genes are cotranscribed as an operon. Expression of aoxAB was monitored by
      RT-PCR and found to be up-regulated by the addition of As(III) to cell cultures.
      Expression of aoxAB was also controlled in a fashion consistent with quorum
      sensing in that (i) expression of aoxAB was absent in As(III)-unexposed early-log
      phase cells but was observed in As(III)-unexposed, late-log-phase cells and (ii)
      treating As(III)-unexposed, early-log-phase cells with ethyl acetate extracts of
      As(III)-unexposed, late-log-phase culture supernatants also resulted in aoxAB
      induction. Under inducing conditions, aoxS expression was readily observed in the
      wild-type strain but significantly reduced in the mutant, indicating that AoxR is
      autoregulatory and at least partially controls the expression of the aox operon.
      In summary, regulation of A. tumefaciens As(III) oxidation is complex, apparently
      being controlled by As(III) exposure, a two-component signal transduction system,
      and quorum sensing.

PMID- 16428413
TI  - Regulation and properties of PstSCAB, a high-affinity, high-velocity phosphate
      transport system of Sinorhizobium meliloti.
AB  - The properties and regulation of the pstSCAB-encoded Pi uptake system from the
      alfalfa symbiont Sinorhizobium meliloti are reported. We present evidence that
      the pstSCAB genes and the regulatory phoUB genes are transcribed from a single
      promoter that contains two PhoB binding sites and that transcription requires
      PhoB. S. meliloti strain 1021 (Rm1021) and its derivatives were found to carry a
      C deletion frameshift mutation in the pstC gene (designated pstC1021) that
      severely impairs activity of the PstSCAB Pi transport system. This mutation is
      absent in RCR2011, the parent of Rm1021. Correction of the pstC1021 mutation in
      Rm1021 by site-directed mutagenesis revealed that PstSCAB is a Pi-specific, high
      affinity (Km, 0.2 microM), high-velocity (Vmax, 70 nmol/min/mg protein) transport
      system. The pstC1021 allele was shown to generate a partial pho regulon
      constitutive phenotype, in which transcription is activated by PhoB even under Pi
      excess conditions that render PhoB inactive in a wild-type background. The
      previously reported symbiotic Fix- phenotype of phoCDET mutants was found to be
      dependent on the pstC1021 mutation, as Rm1021 phoCDET mutants formed small white
      nodules on alfalfa that failed to reduce N2, whereas phoCDET mutant strains with
      a corrected pstC allele (RmP110) formed pink nodules on alfalfa that fixed N2
      like the wild type. Alfalfa root nodules formed by the wild-type RCR2011 strain
      expressed the low-affinity orfA-pit-encoded Pi uptake system and neither the
      pstSCAB genes nor the phoCDET genes. Thus, metabolism of alfalfa nodule
      bacteroids is not Pi limited.

PMID- 16428414
TI  - The Fnr regulon of Bacillus subtilis.
AB  - The Bacillus subtilis transcriptional regulator Fnr is an integral part of the
      regulatory cascade required for the adaptation of the bacterium to low oxygen
      tension. The B. subtilis Fnr regulon was defined via transcriptomic analysis in
      combination with bioinformatic-based binding site prediction. Four distinct
      groups of Fnr-dependent genes were observed. Group 1 genes (narKfnr, narGHJI, and
      arfM) are generally induced by Fnr under anaerobic conditions. All corresponding
      promoters contain an essential Fnr-binding site centered -41.5/-40.5 bp upstream
      of the transcriptional start point, suggesting their induction by direct Fnr
      interaction. Group 2 genes (alsSD, ldh lctP, ywcJ, and cydABCD) are characterized
      by anaerobic repression in the presence of nitrate. Mutational analysis of the
      Fnr-binding sites found in three of the corresponding promoters excluded their
      function in Fnr-mediated repression. Genetic evidence showing that group 2 genes
      are anaerobically repressed by nitrate reductase formation was accumulated. A
      possible role of the redox regulator YdiH in the regulation of group 2 genes was
      initially investigated. Group 3 genes are characterized by their Fnr-dependent
      activation in the presence of nitrate and the lack of an Fnr-binding site in
      their promoters. The analysis of Group 3 gene transcription (ykuNOP and ydbN)
      indicated that Fnr induces nitrate reductase production, which leads to the
      formation of the regulatory compound nitrite from nitrate. Finally, the group 4
      operon acoABCL, lacking an Fnr-binding site, requires Fnr-dependent nitrate
      reductase formation for its general anaerobic induction. A regulatory model for
      the observed complex Fnr-mediated gene expression was deduced.

PMID- 16428415
TI  - Serotype differences and lack of biofilm formation characterize Yersinia
      pseudotuberculosis infection of the Xenopsylla cheopis flea vector of Yersinia
      pestis.
AB  - Yersinia pestis, the agent of plague, is usually transmitted by fleas. To produce
      a transmissible infection, Y. pestis colonizes the flea midgut and forms a
      biofilm in the proventricular valve, which blocks normal blood feeding. The
      enteropathogen Yersinia pseudotuberculosis, from which Y. pestis recently
      evolved, is not transmitted by fleas. However, both Y. pestis and Y.
      pseudotuberculosis form biofilms that adhere to the external mouthparts and block
      feeding of Caenorhabditis elegans nematodes, which has been proposed as a model
      of Y. pestis-flea interactions. We compared the ability of Y. pestis and Y.
      pseudotuberculosis to infect the rat flea Xenopsylla cheopis and to produce
      biofilms in the flea and in vitro. Five of 18 Y. pseudotuberculosis strains,
      encompassing seven serotypes, including all three serotype O3 strains tested,
      were unable to stably colonize the flea midgut. The other strains persisted in
      the flea midgut for 4 weeks but did not increase in numbers, and none of the 18
      strains colonized the proventriculus or produced a biofilm in the flea. Y.
      pseudotuberculosis strains also varied greatly in their ability to produce
      biofilms in vitro, but there was no correlation between biofilm phenotype in
      vitro or on the surface of C. elegans and the ability to colonize or block fleas.
      Our results support a model in which a genetic change in the Y.
      pseudotuberculosis progenitor of Y. pestis extended its pre-existing ex vivo
      biofilm-forming ability to the flea gut environment, thus enabling proventricular
      blockage and efficient flea-borne transmission.

PMID- 16428416
TI  - Overexpression of genes of the cell wall stimulon in clinical isolates of
      Staphylococcus aureus exhibiting vancomycin-intermediate- S. aureus-type
      resistance to vancomycin.
AB  - Custom-designed gene chips (Affymetrix) were used to determine genetic
      relatedness and gene expression profiles in Staphylococcus aureus isolates with
      increasing MICs of vancomycin that were recovered over a period of several weeks
      from the blood and heart valve of a patient undergoing extensive vancomycin
      therapy. The isolates were found to be isogenic as determined by the GeneChip
      based genotyping approach and thus represented a unique opportunity to study
      changes in gene expression that may contribute to the vancomycin resistance
      phenotype. No differences in gene expression were detected between the parent
      strain, JH1, and JH15, isolated from the nares of a patient contact. Few
      expression changes were observed between blood and heart valve isolates with
      identical vancomycin MICs. A large number of genes had altered expression in the
      late stage JH9 isolate (MIC = 8 microg/ml) compared to JH1 (MIC = 1 microg/ml).
      Most genes with altered expression were involved in housekeeping functions or
      cell wall biosynthesis and regulation. The sortase-encoding genes, srtA and srtB,
      as well as several surface protein-encoding genes were downregulated in JH9. Two
      hypothetical protein-encoding genes, SAS016 and SA2343, were dramatically
      overexpressed in JH9. Interestingly, 27 of the genes with altered expression in
      JH9 grown in drug-free medium were found to be also overexpressed when the
      parental strain JH1 was briefly exposed to inhibitory concentrations of
      vancomycin, and more than half (17 of 27) of the genes with altered expression
      belonged to determinants that were proposed to form part of a general cell wall
      stress stimulon (S. Utaida et al., Microbiology 149:2719-2732, 2003).

PMID- 16428417
TI  - Horizontal gene transfer and the evolution of microvirid coliphage genomes.
AB  - Bacteriophage genomic evolution has been largely characterized by rampant,
      promiscuous horizontal gene transfer involving both homologous and nonhomologous
      source DNA. This pattern has emerged through study of the tailed double-stranded
      DNA (dsDNA) phages and is based upon a sparse sampling of the enormous diversity
      of these phages. The single-stranded DNA phages of the family Microviridae,
      including phiX174, appear to evolve through qualitatively different mechanisms,
      possibly as result of their strictly lytic lifestyle and small genome size.
      However, this apparent difference could reflect merely a dearth of relevant data.
      We sought to characterize the forces that contributed to the molecular evolution
      of the Microviridae and to examine the genetic structure of this single family of
      bacteriophage by sequencing the genomes of microvirid phage isolated on a single
      bacterial host. Microvirids comprised 3.5% of the detectable phage in our
      environmental samples, and sequencing yielded 42 new microvirid genomes.
      Phylogenetic analysis of the genes contained in these and five previously
      described microvirid phages identified three distinct clades and revealed at
      least two horizontal transfer events between clades. All members of one clade
      have a block of five putative genes that are not present in any member of the
      other two clades. Our data indicate that horizontal transfer does contribute to
      the evolution of the microvirids but is both quantitatively and qualitatively
      different from what has been observed for the dsDNA phages.

PMID- 16428419
TI  - Steady-state kinetic analysis of phosphotransacetylase from Methanosarcina
      thermophila.
AB  - Phosphotransacetylase (EC 2.3.1.8) catalyzes the reversible transfer of the
      acetyl group from acetyl phosphate to coenzyme A (CoA), forming acetyl-CoA and
      inorganic phosphate. A steady-state kinetic analysis of the phosphotransacetylase
      from Methanosarcina thermophila indicated that there is a ternary complex kinetic
      mechanism rather than a ping-pong kinetic mechanism. Additionally, inhibition
      patterns of products and a nonreactive substrate analog suggested that the
      substrates bind to the enzyme in a random order. Dynamic light scattering
      revealed that the enzyme is dimeric in solution.

PMID- 16428418
TI  - Structural and functional studies suggest a catalytic mechanism for the
      phosphotransacetylase from Methanosarcina thermophila.
AB  - Phosphotransacetylase (EC 2.3.1.8) catalyzes reversible transfer of the acetyl
      group from acetyl phosphate to coenzyme A (CoA), forming acetyl-CoA and inorganic
      phosphate. Two crystal structures of phosphotransacetylase from the methanogenic
      archaeon Methanosarcina thermophila in complex with the substrate CoA revealed
      one CoA (CoA1) bound in the proposed active site cleft and an additional CoA
      (CoA2) bound at the periphery of the cleft. The results of isothermal titration
      calorimetry experiments are described, and they support the hypothesis that there
      are distinct high-affinity (equilibrium dissociation constant [KD], 20 microM)
      and low-affinity (KD, 2 mM) CoA binding sites. The crystal structures indicated
      that binding of CoA1 is mediated by a series of hydrogen bonds and extensive van
      der Waals interactions with the enzyme and that there are fewer of these
      interactions between CoA2 and the enzyme. Different conformations of the protein
      observed in the crystal structures suggest that domain movements which alter the
      geometry of the active site cleft may contribute to catalysis. Kinetic and
      calorimetric analyses of site-specific replacement variants indicated that there
      are catalytic roles for Ser309 and Arg310, which are proximal to the reactive
      sulfhydryl of CoA1. The reaction is hypothesized to proceed through base
      catalyzed abstraction of the thiol proton of CoA by the adjacent and invariant
      residue Asp316, followed by nucleophilic attack of the thiolate anion of CoA on
      the carbonyl carbon of acetyl phosphate. We propose that Arg310 binds acetyl
      phosphate and orients it for optimal nucleophilic attack. The hypothesized
      mechanism proceeds through a negatively charged transition state stabilized by
      hydrogen bond donation from Ser309.

PMID- 16428420
TI  - Suppression of engulfment defects in bacillus subtilis by elevated expression of
      the motility regulon.
AB  - During Bacillus subtilis sporulation, the transient engulfment defect of spoIIB
      strains is enhanced by spoVG null mutations and suppressed by spoVS null
      mutations. These mutations have opposite effects on expression of the motility
      regulon, as the spoVG mutation reduces and the spoVS mutation increases sigmaD
      directed gene expression, cell separation, and autolysis. Elevating sigmaD
      activity by eliminating the anti-sigma factor FlgM also suppresses spoIIB spoVG,
      and both flgM and spoVS mutations cause continued expression of the sigmaD
      regulon during sporulation. We propose that peptidoglycan hydrolases induced
      during motility can substitute for sporulation-specific hydrolases during
      engulfment. We find that sporulating cells are heterogeneous in their expression
      of the motility regulon, which could result in phenotypic variation between
      individual sporulating cells.

PMID- 16428421
TI  - Mutations in the waaR gene of Escherichia coli which disrupt lipopolysaccharide
      outer core biosynthesis affect cell surface retention of group 2 capsular
      polysaccharides.
AB  - On the basis of increased resistance to K5 capsule-specific bacteriophage, a waaR
      transposon mutant defective in the biosynthesis of lipopolysaccharide outer core
      was isolated. In a K1-expressing strain the mutation equally affected sensitivity
      to K1 capsule-specific bacteriophage, indicating a general effect on group 2
      capsules. The waaR mutation affected retention on the cell surface of the K5
      polysaccharide, with increased polysaccharide accumulating in the culture
      supernatant. This indicates that interactions between the outer core of
      lipopolysaccharide and group 2 capsular polysaccharides are important for the
      stabilization of group 2 capsular polysaccharides on the cell surface.

PMID- 16428422
TI  - A bacteroides conjugative transposon, CTnERL, can transfer a portion of itself by
      conjugation without excising from the chromosome.
AB  - CTnERL, a Bacteroides conjugative transposon, transferred DNA by an Hfr-type
      mechanism during conjugation when it was excision deficient due to an insertion
      in the integrase gene. Rescue of the conjugative transposon sequences required
      the recipient to be RecA proficient and to contain an integrated CTnERL. The
      transfer efficiency was only 10- to 30-fold lower than the normal element
      transfer efficiency, and the direction of transfer from the oriT gene showed that
      the integrase end was transferred first and that the transfer genes were
      transferred last.

PMID- 16428423
TI  - Salmonella enterica strains lacking the frataxin homolog CyaY show defects in Fe
      S cluster metabolism in vivo.
AB  - In Salmonella enterica, the isc operon contains genes necessary for the synthesis
      of Fe-S clusters and strains lacking this operon have severe defects in a variety
      of cellular processes. Other cellular loci that impact Fe-S cluster synthesis to
      a lesser extent have been described. The cyaY locus encodes a frataxin homolog,
      and it is shown here that lesions in this locus affect Fe-S cluster metabolism.
      When present in combination with other lesions, mutations in cyaY can result in a
      strain with more severe defects than those lacking the isc locus.

PMID- 16428425
TI  - Comparative genomic analysis of 18 Pseudomonas aeruginosa bacteriophages.
AB  - A genomic analysis of 18 P. aeruginosa phages, including nine newly sequenced DNA
      genomes, indicates a tremendous reservoir of proteome diversity, with 55% of open
      reading frames (ORFs) being novel. Comparative sequence analysis and ORF map
      organization revealed that most of the phages analyzed displayed little
      relationship to each other.

PMID- 16428424
TI  - A pmrA constitutive mutant sensitizes Escherichia coli to deoxycholic acid.
AB  - An Escherichia coli mutant was isolated and shown to be polymyxin B resistant.
      Mapping and sequence analysis revealed a missense mutation at codon 53 within the
      pmrA (basR) gene that results in a G-to-V substitution. Fusions of promoters from
      the pmrC, yibD, and pmrH genes with the lacZ reporter showed that they were
      constitutively expressed in pmrA53 cells. In pmrA+ strains, these promoters were
      induced by iron and zinc, while a DeltapmrA mutation blocked induction. The PmrA
      regulon regulates genes whose products remodel the composition and charge of
      lipid A and hence the barrier properties of the outer membrane. Along these
      lines, the pmrA53 mutant was also found to be hypersensitive to the anionic bile
      detergent deoxycholic acid.

PMID- 16428426
TI  - Topologically fixed SecG is fully functional.
AB  - It has been proposed that the bitopic membrane protein SecG undergoes topology
      inversion during translocation of (pre)proteins via SecYEG. Here we show that
      SecG covalently cross-linked to SecY cannot invert its topology while remaining
      fully functional in protein translocation. Our results strongly disfavor topology
      inversion of SecG during protein translocation.

PMID- 16428427
TI  - Mammalian steroid hormones are substrates for the major RND- and MFS-type
      tripartite multidrug efflux pumps of Escherichia coli.
AB  - A steroid-hormone-dependent growth suppression was observed in Escherichia coli
      efflux-deficient backgrounds containing mutations in the major RND- and MFS-type
      tripartite multidrug efflux systems, AcrAB-TolC and EmrAB-TolC, respectively. In
      addition to their previously known natural steroid spectrum, which includes bile
      acids, both systems were shown to transport the hormones estradiol and
      progesterone, whereas hydrocortisone served as a substrate of only AcrAB-TolC.
      Furthermore, at least two other RND-type pumps, YhiV and AcrD, were capable of
      transporting such hormones when overexpressed on plasmid vectors (with some
      demonstrable specificity observed with AcrD). When this activity was examined in
      a wild-type background, cell-associated estradiol levels remained largely
      unaffected by competition with exogenous bile acids and hydrocortisone, in
      contrast to progesterone, which produced a significant modulation in estradiol
      uptake.

PMID- 16428428
TI  - Transcriptional slippage in mxiE controls transcription and translation of the
      downstream mxiD gene, which encodes a component of the Shigella flexneri type III
      secretion apparatus.
AB  - The Shigella flexneri transcription activator MxiE is produced by transcriptional
      slippage from two overlapping open reading frames. By using plasmids encoding a
      mxiD-lacZ translational fusion, we showed that transcriptional slippage in mxiE
      influences both transcription and translation of the downstream mxiD gene
      encoding an essential component of the type III secretion apparatus.

PMID- 16428429
TI  - Transcriptome analysis applied to survival of Shewanella oneidensis MR-1 exposed
      to ionizing radiation.
AB  - The ionizing radiation (IR) dose that yields 20% survival (D20) of Shewanella
      oneidensis MR-1 is lower by factors of 20 and 200 than those for Escherichia coli
      and Deinococcus radiodurans, respectively. Transcriptome analysis was used to
      identify the genes of MR-1 responding to 40 Gy (D20). We observed the induction
      of 170 genes and repression of 87 genes in MR-1 during a 1-h recovery period
      after irradiation. The genomic response of MR-1 to IR is very similar to its
      response to UV radiation (254 nm), which included induction of systems involved
      in DNA repair and prophage synthesis and the absence of differential regulation
      of tricarboxylic acid cycle activity, which occurs in IR-irradiated D.
      radiodurans. Furthermore, strong induction of genes encoding antioxidant enzymes
      in MR-1 was observed. DNA damage may not be the principal cause of high
      sensitivity to IR, considering that MR-1 carries genes encoding a complex set of
      DNA repair systems and 40 Gy IR induces less than one double-strand break in its
      genome. Instead, a combination of oxidative stress, protein damage, and prophage
      mediated cell lysis during irradiation and recovery might underlie this
      organism's great sensitivity to IR.

PMID- 16428430
TI  - The Vibrio harveyi GTPase CgtAV is essential and is associated with the 50S
      ribosomal subunit.
AB  - It was previously reported that unlike the other obg/cgtA GTPases, the Vibrio
      harveyi cgtAV is not essential. Here we show that cgtAV was not disrupted in
      these studies and is, in fact, essential for viability. Depletion of CgtAV did
      not result in cell elongation. CgtAV is associated with the large ribosomal
      particle. In light of our results, we predict that the V. harveyi CgtAV protein
      plays a similar essential role to that seen for Obg/CgtA proteins in other
      bacteria.

PMID- 16428431
TI  - Tollip regulates proinflammatory responses to interleukin-1 and
      lipopolysaccharide.
AB  - Activation of interleukin-1 (IL-1) receptor (IL-1R), Toll-like receptor 2 (TLR2),
      and TLR4 triggers NF-kappaB and mitogen-activated protein kinase (MAPK)-dependent
      signaling, thereby initiating immune responses. Tollip has been implicated as a
      negative regulator of NF-kappaB signaling triggered by these receptors in in
      vitro studies. Here, deficient mice were used to determine the physiological
      contribution of Tollip to immunity. NF-kappaB, as well as MAPK, signaling
      appeared normal in Tollip-deficient cells stimulated with IL-1beta or the TLR4
      ligand lipopolysaccharide (LPS). Similarly, IL-1beta- and TLR-driven activation
      of dendritic cells and lymphocytes was indistinguishable from wild-type cells. In
      contrast, the production of the proinflammatory cytokines, IL-6 and tumor
      necrosis factor alpha was significantly reduced after IL-1beta and LPS treatment
      at low doses but not at lethal doses of LPS. Tollip therefore controls the
      magnitude of inflammatory cytokine production in response to IL-1beta and LPS.

PMID- 16428433
TI  - Study of long-distance functional interactions between Su(Hw) insulators that can
      regulate enhancer-promoter communication in Drosophila melanogaster.
AB  - The Su(Hw) insulator found in the gypsy retrotransposon is the most potent
      enhancer blocker in Drosophila melanogaster. However, two such insulators in
      tandem do not prevent enhancer-promoter communication, apparently because of
      their pairing interaction that results in mutual neutralization. Furthering our
      studies of the role of insulators in the control of gene expression, here we
      present a functional analysis of a large set of transgenic constructs with
      various arrangements of regulatory elements, including two or three insulators.
      We demonstrate that their interplay can have quite different outcomes depending
      on the order of and distance between elements. Thus, insulators can interact with
      each other over considerable distances, across interposed enhancers or promoters
      and coding sequences, whereby enhancer blocking may be attenuated, cancelled, or
      restored. Some inferences concerning the possible modes of insulator action are
      made from collating the new data and the relevant literature, with tentative
      schemes illustrating the regulatory situations in particular model constructs.

PMID- 16428432
TI  - Translational regulation of nuclear gene COX4 expression by mitochondrial content
      of phosphatidylglycerol and cardiolipin in Saccharomyces cerevisiae.
AB  - Previous results indicated that translation of four mitochondrion-encoded genes
      and one nucleus-encoded gene (COX4) is repressed in mutants (pgs1Delta) of
      Saccharomyces cerevisiae lacking phosphatidylglycerol and cardiolipin. COX4
      translation was studied here using a mitochondrially targeted green fluorescence
      protein (mtGFP) fused to the COX4 promoter and its 5' and 3' untranslated regions
      (UTRs). Lack of mtGFP expression independent of carbon source and strain
      background was established to be at the translational level. The translational
      defect was not due to deficiency of mitochondrial respiratory function but was
      rather caused directly by the lack of phosphatidylglycerol and cardiolipin in
      mitochondrial membranes. Reintroduction of a functional PGS1 gene under control
      of the ADH1 promoter restored phosphatidylglycerol synthesis and expression of
      mtGFP. Deletion analysis of the 5' UTR(COX4) revealed the presence of a 50
      nucleotide fragment with two stem-loops as a cis-element inhibiting COX4
      translation. Binding of a protein factor(s) specifically to this sequence was
      observed with cytoplasm from pgs1Delta but not PGS1 cells. Using HIS3 and lacZ as
      reporters, extragenic spontaneous recessive mutations that allowed expression of
      His3p and beta-galactosidase were isolated, which appeared to be loss-of-function
      mutations, suggesting that the genes mutated may encode the trans factors that
      bind to the cis element in pgs1Delta cells.

PMID- 16428434
TI  - Proteomic analysis of mitochondrial protein turnover: identification of novel
      substrate proteins of the matrix protease pim1.
AB  - ATP-dependent oligomeric proteases are major components of cellular protein
      quality control systems. To investigate the role of proteolytic processes in the
      maintenance of mitochondrial functions, we analyzed the dynamic behavior of the
      mitochondrial proteome of Saccharomyces cerevisiae by two-dimensional (2D)
      polyacrylamide gel electrophoresis. By a characterization of the influence of
      temperature on protein turnover in isolated mitochondria, we were able to define
      four groups of proteins showing a differential susceptibility to proteolysis. The
      protein Pim1/LON has been shown to be the main protease in the mitochondrial
      matrix responsible for the removal of damaged or nonnative proteins. To assess
      the substrate range of Pim1 under in vivo conditions, we performed a quantitative
      comparison of the 2D protein spot patterns between wild-type and pim1Delta
      mitochondria. We were able to identify a novel subset of mitochondrial proteins
      that are putative endogenous substrates of Pim1. Using an in organello
      degradation assay, we confirmed the Pim1-specific, ATP-dependent proteolysis of
      the newly identified substrate proteins. We could demonstrate that the functional
      integrity of the Pim1 substrate proteins, in particular, the presence of intact
      prosthetic groups, had a major influence on the susceptibility to proteolysis.

PMID- 16428435
TI  - Cyclin-dependent kinase 9 (Cdk9) of fission yeast is activated by the CDK
      activating kinase Csk1, overlaps functionally with the TFIIH-associated kinase
      Mcs6, and associates with the mRNA cap methyltransferase Pcm1 in vivo.
AB  - Cyclin-dependent kinase 9 (Cdk9) of fission yeast is an essential ortholog of
      metazoan positive transcription elongation factor b (P-TEFb), which is proposed
      to coordinate capping and elongation of RNA polymerase II (Pol II) transcripts.
      Here we show that Cdk9 is activated to phosphorylate Pol II and the elongation
      factor Spt5 by Csk1, one of two fission yeast CDK-activating kinases (CAKs).
      Activation depends on Cdk9 T-loop residue Thr-212. The other CAK-Mcs6, the kinase
      component of transcription factor IIH (TFIIH)-cannot activate Cdk9. Consistent
      with the specificities of the two CAKs in vitro, the kinase activity of Cdk9 is
      reduced approximately 10-fold by csk1 deletion, and Cdk9 complexes from csk1Delta
      but not csk1+ cells can be activated by Csk1 in vitro. A cdk9(T212A) mutant is
      viable but phenocopies conditional growth defects of csk1Delta strains,
      indicating a role for Csk1-dependent activation of Cdk9 in vivo. A cdk9(T212A)
      mcs6(S165A) strain, in which neither Cdk9 nor Mcs6 can be activated by CAK, has a
      synthetic growth defect, implying functional overlap between the two CDKs, which
      have distinct but overlapping substrate specificities. Cdk9 forms complexes in
      vivo with the essential cyclin Pch1 and with Pcm1, the mRNA cap
      methyltransferase. The carboxyl-terminal region of Cdk9, through which it
      interacts with another capping enzyme, the RNA triphosphatase Pct1, is essential.
      Together, the data support a proposed model whereby Cdk9/Pch1-the third essential
      CDK-cyclin complex described in fission yeast-helps to target the capping
      apparatus to the transcriptional elongation complex.

PMID- 16428437
TI  - E2A and IRF-4/Pip promote chromatin modification and transcription of the
      immunoglobulin kappa locus in pre-B cells.
AB  - The immunoglobulin kappa light chain (Igkappa) locus is regulated in a lineage-
      and stage-specific manner during B-cell development. The highly restricted timing
      of V to J gene recombination at the pre-B-cell stage is under the control of two
      enhancers, the intronic enhancer (kappaEi) and the 3' enhancer (kappaE3'),
      flanking the constant exon. E2A transcription factors have been indicated to be
      directly involved in the regulation of Igkappa locus activation. In this study,
      we utilize E2A-deficient pre-B cells to directly investigate the mechanism of E2A
      mediated Igkappa activation. We demonstrate that Igkappa germ line transcription
      is severely impaired and recombination is blocked in the absence of E2A.
      Reconstitution of E2A-/- pre-B cells with inducible human E2A (E47R) is
      sufficient to promote chromatin modification of Igkappa and rescue Igkappa germ
      line transcription and Jkappa gene recombinase accessibility. Furthermore, we
      show that increased E2A recruitment to kappaEi and kappaE3' correlates with
      activation of Igkappa in pre-B cells and that recruitment of E2A to kappaE3' is
      in part dependent on the transcription factor IRF-4. Inhibition of IRF-4
      expression in pre-B cells leads to a significant reduction of Igkappa germ line
      transcription and enhancer acetylation. In the absence of E2A, increased IRF-4
      expression is not sufficient to promote Igkappa enhancer chromatin modification
      or transcription, suggesting that the sequential involvement of IRF-4 and E2A is
      necessary for the activation of the Igkappa locus. Finally, we provide genetic
      evidence in the mouse that E2A gene dosage can influence the development of pre-B
      cells during the phase of Igkappa gene activation.

PMID- 16428438
TI  - Doa1 is a Cdc48 adapter that possesses a novel ubiquitin binding domain.
AB  - Cdc48 (p97/VCP) is an AAA-ATPase molecular chaperone whose cellular functions are
      facilitated by its interaction with ubiquitin binding cofactors (e.g., Npl4-Ufd1
      and Shp1). Several studies have shown that Saccharomyces cerevisiae Doa1
      (Ufd3/Zzz4) and its mammalian homologue, PLAA, interact with Cdc48. However, the
      function of this interaction has not been determined, nor has a physiological
      link between these proteins been demonstrated. Herein, we demonstrate that Cdc48
      interacts directly with the C-terminal PUL domain of Doa1. We find that Doa1
      possesses a novel ubiquitin binding domain (we propose the name PFU domain, for
      PLAA family ubiquitin binding domain), which appears to be necessary for Doa1
      function. Our data suggest that the PUL and PFU domains of Doa1 promote the
      formation of a Doa1-Cdc48-ubiquitin ternary complex, potentially allowing for the
      recruitment of ubiquitinated proteins to Cdc48. DOA1 and CDC48 mutations are
      epistatic, suggesting that their interaction is physiologically relevant. Lastly,
      we provide evidence of functional conservation within the PLAA family by showing
      that a human-yeast chimera binds to ubiquitin and complements doa1Delta
      phenotypes in yeast. Combined, our data suggest that Doa1 plays a physiological
      role as a ubiquitin binding cofactor of Cdc48 and that human PLAA may play an
      analogous role via its interaction with p97/VCP.

PMID- 16428436
TI  - Conditional knockout mice reveal distinct functions for the global
      transcriptional coactivators CBP and p300 in T-cell development.
AB  - The global transcriptional coactivators CREB-binding protein (CBP) and the
      closely related p300 interact with over 312 proteins, making them among the most
      heavily connected hubs in the known mammalian protein-protein interactome. It is
      largely uncertain, however, if these interactions are important in specific cell
      lineages of adult animals, as homozygous null mutations in either CBP or p300
      result in early embryonic lethality in mice. Here we describe a Cre/LoxP
      conditional p300 null allele (p300flox) that allows for the temporal and tissue
      specific inactivation of p300. We used mice carrying p300flox and a CBP
      conditional knockout allele (CBPflox) in conjunction with an Lck-Cre transgene to
      delete CBP and p300 starting at the CD4- CD8- double-negative thymocyte stage of
      T-cell development. Loss of either p300 or CBP led to a decrease in CD4+ CD8+
      double-positive thymocytes, but an increase in the percentage of CD8+ single
      positive thymocytes seen in CBP mutant mice was not observed in p300 mutants. T
      cells completely lacking both CBP and p300 did not develop normally and were
      nonexistent or very rare in the periphery, however. T cells lacking CBP or p300
      had reduced tumor necrosis factor alpha gene expression in response to phorbol
      ester and ionophore, while signal-responsive gene expression in CBP- or p300
      deficient macrophages was largely intact. Thus, CBP and p300 each supply a
      surprising degree of redundant coactivation capacity in T cells and macrophages,
      although each gene has also unique properties in thymocyte development.

PMID- 16428439
TI  - Essential role for Rac in heregulin beta1 mitogenic signaling: a mechanism that
      involves epidermal growth factor receptor and is independent of ErbB4.
AB  - Heregulins are a family of ligands for the ErbB3/ErbB4 receptors that play
      important roles in breast cancer cell proliferation and tumorigenesis. Limited
      information is available on the contribution of Rho GTPases to heregulin-mediated
      signaling. In breast cancer cells, heregulin beta1 (HRG) causes a strong
      activation of Rac; however, it does so with striking differences in kinetics
      compared to epidermal growth factor, which signals through ErbB1 (epidermal
      growth factor receptor [EGFR]). Using specific ErbB receptor inhibitors and
      depletion of receptors by RNA interference (RNAi), we established that,
      surprisingly, activation of Rac by HRG is mediated not only by ErbB3 and ErbB2
      but also by transactivation of EGFR, and it is independent of ErbB4. Similar
      receptor requirements are observed for HRG-induced actin cytoskeleton
      reorganization and mitogenic activity via extracellular signal-regulated kinase
      (ERK). HRG-induced Rac activation was phosphatidylinositol 3-kinase dependent and
      Src independent. Furthermore, inactivation of Rac by expression of the Rac GTPase
      activating protein beta2-chimerin inhibited HRG-induced ERK activation,
      mitogenicity, and migration in breast cancer cells. HRG mitogenic activity was
      also impaired by depletion of Rac1 using RNAi. Our studies established that Rac
      is a critical mediator of HRG mitogenic signaling in breast cancer cells and
      highlight additional levels of complexity for ErbB receptor coupling to
      downstream effectors that control aberrant proliferation and transformation.

PMID- 16428440
TI  - MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and
      functional properties.
AB  - The human genome contains a number of methyl CpG binding proteins that translate
      DNA methylation into a physiological response. To gain insight into the function
      of MBD2 and MBD3, we first applied protein tagging and mass spectrometry. We show
      that MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like
      complexes, called MBD2/NuRD and MBD3/NuRD. We identified DOC-1, a putative tumor
      suppressor, as a novel core subunit of MBD2/NuRD as well as MBD3/NuRD. PRMT5 and
      its cofactor MEP50 were identified as specific MBD2/NuRD interactors. PRMT5
      stably and specifically associates with and methylates the RG-rich N terminus of
      MBD2. Chromatin immunoprecipitation experiments revealed that PRMT5 and MBD2 are
      recruited to CpG islands in a methylation-dependent manner in vivo and that H4R3,
      a substrate of PRMT, is methylated at these loci. Our data show that MBD2/NuRD
      and MBD3/NuRD are distinct protein complexes with different biochemical and
      functional properties.

PMID- 16428441
TI  - Cell cycle requirements in assembling silent chromatin in Saccharomyces
      cerevisiae.
AB  - The establishment of silencing at the silent mating-type locus, HMR, in
      Saccharomyces cerevisiae requires that yeast pass through S phase of the cell
      cycle, yet requires neither the initiation of DNA replication at the locus
      destined to become silenced nor the passage of a replication fork through that
      locus. We tested whether this S-phase requirement reflects a window within the
      cell cycle permissive for recruitment of Sir proteins to HMR. The S-phase
      restricted event necessary for silencing occurred after recruitment of Sir
      proteins to HMR. Moreover, cells arrested in early S phase formed silent
      chromatin at HMR, provided HMR was on a nonreplicating template. Replicating
      templates required a later step for silencing. These results provide temporal
      resolution of discrete steps in the formation of silent chromatin and suggest
      that more than one cell cycle-regulated event may be necessary for the
      establishment of silencing.

PMID- 16428442
TI  - Real-time monitoring of chloroplast gene expression by a luciferase reporter:
      evidence for nuclear regulation of chloroplast circadian period.
AB  - Chloroplast-encoded genes, like nucleus-encoded genes, exhibit circadian
      expression. How the circadian clock exerts its control over chloroplast gene
      expression, however, is poorly understood. To facilitate the study of chloroplast
      circadian gene expression, we developed a codon-optimized firefly luciferase gene
      for the chloroplast of Chlamydomonas reinhardtii as a real-time bioluminescence
      reporter and introduced it into the chloroplast genome. The bioluminescence of
      the reporter strain correlated well with the circadian expression pattern of the
      introduced gene and satisfied all three criteria for circadian rhythms. Moreover,
      the period of the rhythm was lengthened in per mutants, which are phototactic
      rhythm mutants carrying a long-period gene in their nuclear genome. These results
      demonstrate that chloroplast gene expression rhythm is a bona fide circadian
      rhythm and that the nucleus-encoded circadian oscillator determines the period
      length of the chloroplast rhythm. Our reporter strains can serve as a powerful
      tool not only for analysis of the circadian regulation mechanisms of chloroplast
      gene expression but also for a genetic approach to the molecular oscillator of
      the algal circadian clock.

PMID- 16428443
TI  - Host cell factor and an uncharacterized SANT domain protein are stable components
      of ATAC, a novel dAda2A/dGcn5-containing histone acetyltransferase complex in
      Drosophila.
AB  - Gcn5 is a conserved histone acetyltransferase (HAT) found in a number of
      multisubunit complexes from Saccharomyces cerevisiae, mammals, and flies. We
      previously identified Drosophila melanogaster homologues of the yeast proteins
      Ada2, Ada3, Spt3, and Tra1 and showed that they associate with dGcn5 to form at
      least two distinct HAT complexes. There are two different Ada2 homologues in
      Drosophila named dAda2A and dAda2B. dAda2B functions within the Drosophila
      version of the SAGA complex (dSAGA). To gain insight into dAda2A function, we
      sought to identify novel components of the complex containing this protein, ATAC
      (Ada two A containing) complex. Affinity purification and mass spectrometry
      revealed that, in addition to dAda3 and dGcn5, host cell factor (dHCF) and a
      novel SANT domain protein, named Atac1 (ATAC component 1), copurify with this
      complex. Coimmunoprecipitation experiments confirmed that these proteins
      associate with dGcn5 and dAda2A, but not with dSAGA-specific components such as
      dAda2B and dSpt3. Biochemical fractionation revealed that ATAC has an apparent
      molecular mass of 700 kDa and contains dAda2A, dGcn5, dAda3, dHCF, and Atac1 as
      stable subunits. Thus, ATAC represents a novel histone acetyltransferase complex
      that is distinct from previously purified Gcn5/Pcaf-containing complexes from
      yeast and mammalian cells.

PMID- 16428445
TI  - Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating
      focal adhesions.
AB  - h-prune, which has been suggested to be involved in cell migration, was
      identified as a glycogen synthase kinase 3 (GSK-3)-binding protein. Treatment of
      cultured cells with GSK-3 inhibitors or small interfering RNA (siRNA) for GSK-3
      and h-prune inhibited their motility. The kinase activity of GSK-3 was required
      for the interaction of GSK-3 with h-prune. h-prune was localized to focal
      adhesions, and the siRNA for GSK-3 or h-prune delayed the disassembly of
      paxillin. The tyrosine phosphorylation of focal adhesion kinase (FAK) and the
      activation of Rac were suppressed in GSK-3 or h-prune knocked-down cells. GSK-3
      inhibitors suppressed the disassembly of paxillin and the activation of FAK and
      Rac. Furthermore, h-prune was highly expressed in colorectal and pancreatic
      cancers, and the positivity of the h-prune expression was correlated with tumor
      invasion. These results suggest that GSK-3 and h-prune cooperatively regulate the
      disassembly of focal adhesions to promote cell migration and that h-prune is
      useful as a marker for tumor aggressiveness.

PMID- 16428444
TI  - Mxr1p, a key regulator of the methanol utilization pathway and peroxisomal genes
      in Pichia pastoris.
AB  - Growth of the yeast Pichia pastoris on methanol induces the expression of genes
      whose products are required for its metabolism. Three of the methanol pathway
      enzymes are located in an organelle called the peroxisome. As a result, both
      methanol pathway enzymes and proteins involved in peroxisome biogenesis (PEX
      proteins) are induced in response to this substrate. The most highly regulated of
      these genes is AOX1, which encodes alcohol oxidase, the first enzyme of the
      methanol pathway, and a peroxisomal enzyme. To elucidate the molecular mechanisms
      responsible for methanol regulation, we identify genes required for the
      expression of AOX1. Mutations in one gene, named MXR1 (methanol expression
      regulator 1), result in strains that are unable to (i) grow on the peroxisomal
      substrates methanol and oleic acid, (ii) induce the transcription of AOX1 and
      other methanol pathway and PEX genes, and (iii) form normal-appearing peroxisomes
      in response to methanol. MXR1 encodes a large protein with a zinc finger DNA
      binding domain near its N terminus that has similarity to Saccharomyces
      cerevisiae Adr1p. In addition, Mxr1p is localized to the nucleus in cells grown
      on methanol or other gluconeogenic substrates. Finally, Mxr1p specifically binds
      to sequences upstream of AOX1. We conclude that Mxr1p is a transcription factor
      that is necessary for the activation of many genes in response to methanol. We
      propose that MXR1 is the P. pastoris homologue of S. cerevisiae ADR1 but that it
      has gained new functions and lost others through evolution as a result of changes
      in the spectrum of genes that it controls.

PMID- 16428446
TI  - The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the
      plasma membrane in the filamentous growth signaling pathway of the yeast
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, pheromone response requires Ste5 scaffold protein,
      which ensures efficient G-protein-dependent recruitment of mitogen-activated
      protein kinase (MAPK) cascade components Ste11 (MAPK kinase kinase), Ste7 (MAPK
      kinase), and Fus3 (MAPK) to the plasma membrane for activation by Ste20 protein
      kinase. Ste20, which phosphorylates Ste11 to initiate signaling, is activated by
      binding to Cdc42 GTPase (membrane anchored via its C-terminal
      geranylgeranylation). Less clear is how activated and membrane-localized Ste20
      contacts Ste11 to trigger invasive growth signaling, which also requires Ste7 and
      the MAPK Kss1, but not Ste5. Ste50 protein associates constitutively via an N
      terminal sterile-alpha motif domain with Ste11, and this interaction is required
      for optimal invasive growth and hyperosmotic stress (high-osmolarity glycerol
      [HOG]) signaling but has a lesser role in pheromone response. We show that a
      conserved C-terminal, so-called "Ras association" (RA) domain in Ste50 is also
      essential for invasive growth and HOG signaling in vivo. In vitro the Ste50 RA
      domain is not able to associate with Ras2, but it does associate with Cdc42 and
      binds to a different face than does Ste20. RA domain function can be replaced by
      the nine C-terminal, plasma membrane-targeting residues (KKSKKCAIL) of Cdc42, and
      membrane-targeted Ste50 also suppresses the signaling deficiency of cdc42 alleles
      specifically defective in invasive growth. Thus, Ste50 serves as an adaptor to
      tether Ste11 to the plasma membrane and can do so via association with Cdc42,
      thereby permitting the encounter of Ste11 with activated Ste20.

PMID- 16428447
TI  - Activation of beta-catenin signaling in prostate cancer by peptidyl-prolyl
      isomerase Pin1-mediated abrogation of the androgen receptor-beta-catenin
      interaction.
AB  - Androgen receptor (AR) interacts with beta-catenin and can suppress its
      coactivation of T cell factor 4 (Tcf4) in prostate cancer (PCa) cells. Pin1 is a
      peptidyl-prolyl cis/trans isomerase that stabilizes beta-catenin by inhibiting
      its binding to the adenomatous polyposis coli gene product and subsequent
      glycogen synthase kinase 3beta (GSK-3beta)-dependent degradation. Higher Pin1
      expression in primary PCa is correlated with disease recurrence, and this study
      found that Pin1 expression was markedly increased in metastatic PCa. Consistent
      with this result, increased expression of Pin1 in transfected LNCaP PCa cells
      strongly accelerated tumor growth in vivo in immunodeficient mice. Pin1
      expression in LNCaP cells enhanced beta-catenin/Tcf4 transcriptional activity, as
      assessed using Tcf4-regulated reporter genes, and increased expression of
      endogenous Tcf4 and c-myc. However, in contrast to results in cells with intact
      PTEN and active GSK-3beta, Pin1 expression in LNCaP PCa cells, which are PTEN
      deficient, did not increase beta-catenin. Instead, Pin1 expression markedly
      inhibited the beta-catenin interaction with AR, and Pin1 abrogated the ability of
      AR to antagonize beta-catenin/Tcf4 binding and transcriptional activity. These
      findings demonstrate that AR can suppress beta-catenin signaling, that the AR
      beta-catenin interaction can be regulated by Pin1, and that abrogation of this
      interaction can enhance beta-catenin/Tcf4 signaling and contribute to aggressive
      biological behavior in PCa.

PMID- 16428448
TI  - Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in Nrf2 null
      mice.
AB  - Genetic and biochemical analyses have uncovered an essential role for nuclear
      factor erythroid 2-related factor 2 (Nrf2) in regulating phase II xenobiotic
      metabolism and antioxidant response. Here we show that Nrf2 protects against the
      ovarian toxicity of 4-vinylcyclohexene diepoxide (VCD) in mice. Nrf2-/- female
      mice exposed to VCD exhibit an age-dependent decline in reproduction leading to
      secondary infertility accompanied by hypergonadotropic hypogonadism after 30
      weeks of age. VCD is shown to selectively destroy small ovarian follicles,
      resulting in early depletion of functional follicles. Treatment with VCD induces
      apoptotic death in cultured cells and in ovarian follicles, suggesting apoptosis
      as a mechanism of follicle loss. Loss of Nrf2 function blocks the basal and
      inducible expression of microsomal epoxide hydrolase, a key enzyme in the
      detoxification of VCD, and increases the oxidative stress in cells that is
      further exacerbated by VCD. Foxo3a, a repressor in the early stages of follicle
      activation, displays reduced expression in Nrf2-/- ovaries, causing accelerated
      growth of follicles in the absence of exposure to exogenous chemicals.
      Furthermore, Foxo3a is degraded through the 26S proteasome pathway in untreated
      cells and is induced by VCD via both Nrf2-dependent transcription and protein
      stabilization. This study demonstrates that Nrf2 serves as an essential sensor
      and regulator of chemical homeostasis in ovarian cells, protecting the cells from
      toxic chemicals by controlling metabolic detoxification, reactive oxygen species
      defense, and Foxo3a expression. In addition, these findings raise the possibility
      that exposure to environmental or occupational ovotoxicants plays a role in the
      premature ovarian failure commonly associated with infertility and premature
      aging in women.

PMID- 16428449
TI  - Inhibition of DNA binding by differential sumoylation of heat shock factors.
AB  - Covalent modification of proteins by the small ubiquitin-related modifier SUMO
      regulates diverse biological functions. Sumoylation usually requires a consensus
      tetrapeptide, through which the binding of the SUMO-conjugating enzyme Ubc9 to
      the target protein is directed. However, additional specificity determinants are
      in many cases required. To gain insights into SUMO substrate selection, we have
      utilized the differential sumoylation of highly similar loop structures within
      the DNA-binding domains of heat shock transcription factor 1 (HSF1) and HSF2.
      Site-specific mutagenesis in combination with molecular modeling revealed that
      the sumoylation specificity is determined by several amino acids near the
      consensus site, which are likely to present the SUMO consensus motif to Ubc9.
      Importantly, we also demonstrate that sumoylation of the HSF2 loop impedes HSF2
      DNA-binding activity, without affecting its oligomerization. Hence, SUMO
      modification of the HSF2 loop contributes to HSF-specific regulation of DNA
      binding and broadens the concept of sumoylation in the negative regulation of
      gene expression.

PMID- 16428450
TI  - Phenotypic analysis of mice lacking the Tmprss2-encoded protease.
AB  - Tmprss2 encodes an androgen-regulated type II transmembrane serine protease
      (TTSP) expressed highly in normal prostate epithelium and has been implicated in
      prostate carcinogenesis. Although in vitro studies suggest protease-activated
      receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of
      TMPRSS2 remain unknown. We generated Tmprss2-/- mice by disrupting the serine
      protease domain through homologous recombination. Compared to wild-type
      littermates, Tmprss2-/- mice developed normally, survived to adulthood with no
      differences in protein levels of prostatic secretions, and exhibited no
      discernible abnormalities in organ histology or function. Loss of TMPRSS2 serine
      protease activity did not influence fertility, reduce survival, result in
      prostate hyperplasia or carcinoma, or alter prostatic luminal epithelial cell
      regrowth following castration and androgen replacement. Lack of an observable
      phenotype in Tmprss2-/- mice was not due to transcriptional compensation by
      closely related Tmprss2 homologs. We conclude that the lack of a discernible
      phenotype in Tmprss2-/- mice suggests functional redundancy involving one or more
      of the type II transmembrane serine protease family members or other serine
      proteases. Alternatively, TMPRSS2 may contribute a specialized but nonvital
      function that is apparent only in the context of stress, disease, or other
      systemic perturbation.

PMID- 16428452
TI  - TGIF inhibits retinoid signaling.
AB  - TGIF (TG-interacting factor) represses transforming growth factor beta (TGF-beta)
      activated gene expression and can repress transcription via a specific retinoid
      response element. Mutations in human TGIF are associated with holoprosencephaly,
      a severe defect of craniofacial development with both genetic and environmental
      causes. Both TGF-beta and retinoic acid signaling are implicated in craniofacial
      development. Here, we analyze the role of TGIF in regulating retinoid responsive
      gene expression. We demonstrate that TGIF interacts with the ligand binding
      domain of the RXRalpha retinoid receptor and represses transcription from
      retinoid response elements. TGIF recruits the general corepressor, CtBP, to
      RXRalpha, and this recruitment is required for full repression by TGIF.
      Interaction between TGIF and RXRalpha is reduced by the addition of retinoic
      acid, consistent with a role for TGIF as an RXRalpha transcriptional corepressor.
      We created a Tgif null mutation in mice and tested the sensitivity of mutant mice
      to increased levels of retinoic acid. Tgif mutant embryos are more sensitive to
      retinoic acid-induced teratogenesis, and retinoid target genes are expressed at a
      higher level in tissues from Tgif null mice. These results demonstrate an
      important role for TGIF as a transcriptional corepressor, which regulates
      developmental signaling by retinoic acid, and raises the possibility that TGIF
      may repress other RXR-dependent transcriptional responses.

PMID- 16428451
TI  - Differential contributions of mammalian Rad54 paralogs to recombination, DNA
      damage repair, and meiosis.
AB  - Homologous recombination is a versatile DNA damage repair pathway requiring Rad51
      and Rad54. Here we show that a mammalian Rad54 paralog, Rad54B, displays physical
      and functional interactions with Rad51 and DNA that are similar to those of
      Rad54. While ablation of Rad54 in mouse embryonic stem (ES) cells leads to a mild
      reduction in homologous recombination efficiency, the absence of Rad54B has
      little effect. However, the absence of both Rad54 and Rad54B dramatically reduces
      homologous recombination efficiency. Furthermore, we show that Rad54B protects ES
      cells from ionizing radiation and the interstrand DNA cross-linking agent
      mitomycin C. Interestingly, at the ES cell level the paralogs do not display an
      additive or synergic interaction with respect to mitomycin C sensitivity, yet
      animals lacking both Rad54 and Rad54B are dramatically sensitized to mitomycin C
      compared to either single mutant. This suggests that the paralogs possibly
      function in a tissue-specific manner. Finally, we show that Rad54, but not
      Rad54B, is needed for a normal distribution of Rad51 on meiotic chromosomes.
      Thus, even though the paralogs have similar biochemical properties, genetic
      analysis in mice uncovered their nonoverlapping roles.

PMID- 16428454
TI  - Global analysis of the relationship between the binding of the Bas1p
      transcription factor and meiosis-specific double-strand DNA breaks in
      Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, certain genomic regions have very high
      levels of meiotic recombination (hot spots). The hot spot activity associated
      with the HIS4 gene requires the Bas1p transcription factor. To determine whether
      this relationship between transcription factor binding and hot spot activity is
      general, we used DNA microarrays to map all genomic Bas1p binding sites and to
      map the frequency of meiosis-specific double-strand DNA breaks (as an estimate of
      the recombination activity) of all genes in both wild-type and bas1 strains. We
      identified sites of Bas1p-DNA interactions upstream of 71 genes, many of which
      are involved in histidine and purine biosynthesis. Our analysis of recombination
      activity in wild-type and bas1 strains showed that the recombination activities
      of some genes with Bas1p binding sites were dependent on Bas1p (as observed for
      HIS4), whereas the activities of other genes with Bas1p binding sites were
      unaffected or were repressed by Bas1p. These data demonstrate that the effect of
      transcription factors on meiotic recombination activity is strongly context
      dependent. In wild-type and bas1 strains, meiotic recombination was strongly
      suppressed in large (25- to 150-kb) chromosomal regions near the telomeres and
      centromeres and in the region flanking the rRNA genes. These results argue that
      both local and regional factors affect the level of meiotic recombination.

PMID- 16428453
TI  - Receptor activator of NF-kappaB ligand regulates the proliferation of mammary
      epithelial cells via Id2.
AB  - Receptor activator of NF-kappaB ligand (RANKL) is a key regulator for mammary
      gland development during pregnancy. RANKL-deficient mice display impaired
      development of lobulo-alveolar mammary structures. Similar mammary gland defects
      have been reported in mice lacking Id2. Here we report that RANKL induces the
      proliferation of mammary epithelial cells via Id2. RANKL triggers marked nuclear
      translocation of Id2 in mammary epithelial cells. In vivo studies further
      demonstrated the defective nuclear translocation of Id2, but the normal
      expression of cyclin D1, in the mammary epithelial cells of rankl-/- mice. In
      vitro studies with nuclear localization sequence-tagged Id2 revealed that the
      nuclear localization of Id2 itself is critical for the downregulation of p21
      promoter activity. Moreover, RANKL stimulation failed to induce cell growth and
      to downregulate p21 expression in Id2-/- mammary epithelial cells. Our results
      indicate that the inhibitor of helix-loop-helix protein, Id2, is critical to
      control the proliferation of mammary epithelial cells in response to RANKL
      stimulation.

PMID- 16428455
TI  - The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is
      dispensable for C/EBPalpha-mediated growth regulation in vivo.
AB  - The C/EBPalpha transcription factor regulates growth and differentiation of
      several tissues during embryonic development. Several hypotheses as to how
      C/EBPalpha inhibits cellular growth in vivo have been derived, mainly from
      studies of tissue culture cells. In fetal liver it has been proposed that a
      short, centrally located, 15-amino-acid proline-histidine-rich region (PHR) of
      C/EBPalpha is responsible for the growth-inhibitory function of the protein
      through its ability to interact with CDK2 and CDK4, thereby inhibiting their
      activities. Homozygous Cebpa(DeltaPHR/DeltaPHR) (DeltaPHR) mice, carrying a
      modified cebpa allele lacking amino acids 180 to 194, were born at the Mendelian
      ratio, reached adulthood, and displayed no apparent adverse phenotypes. When
      fetal livers from the DeltaPHR mice were analyzed for their expression of cell
      cycle markers, bromodeoxyuridine incorporation, cyclin-dependent kinase 2 kinase
      activity, and global gene expression, we failed to detect any cell cycle or
      developmental differences between the DeltaPHR mice and their control
      littermates. These in vivo data demonstrate that any C/EBPalpha-mediated growth
      repression via the PHR as well as the basic region is dispensable for proper
      embryonic development of, and cell cycle control in, the liver. Surprisingly,
      control experiments performed in C/EBPalpha null fetal livers yielded similar
      results.

PMID- 16428456
TI  - Low K+ promotes NF-kappaB/DNA binding in neuronal apoptosis induced by K+ loss.
AB  - Low intracellular K+ concentration ([K+]i) promotes apoptosis and blocking K+
      loss prevents apoptosis, but the mechanism of action of low [K+]i remains
      unclear. Here, we show that low [K+]i increases NF-kappaB transcriptional
      activity by enhancing its binding to the promoter of target genes without
      affecting its activation and nuclear translocation in cortical neurons deprived
      of serum. Low K+ concentration promotes NF-kappaB/DNA binding through direct
      effects on the interaction of NF-kappaB dimers with DNA. Up-regulation of
      proapoptotic protein Bcl-XS and neuronal apoptosis induced by serum deprivation
      are blocked by inhibition and/or down-regulation of NF-kappaB and by prevention
      of K+ loss. Thus, a direct action of K+ on NF-kappaB/DNA binding regulates gene
      transcription related to neuronal apoptosis.

PMID- 16428457
TI  - The Chinese hamster dihydrofolate reductase replication origin decision point
      follows activation of transcription and suppresses initiation of replication
      within transcription units.
AB  - Chinese hamster ovary (CHO) cells select specific replication origin sites within
      the dihydrofolate reductase (DHFR) locus at a discrete point during G1 phase, the
      origin decision point (ODP). Origin selection is sensitive to transcription but
      not protein synthesis inhibitors, implicating a pretranslational role for
      transcription in origin specification. We have constructed a DNA array covering
      121 kb surrounding the DHFR locus, to comprehensively investigate replication
      initiation and transcription in this region. When nuclei isolated within the
      first 3 h of G1 phase were stimulated to initiate replication in Xenopus egg
      extracts, replication initiated without any detectable preference for specific
      sites. At the ODP, initiation became suppressed from within the Msh3, DHFR, and
      2BE2121 transcription units. Active transcription was mostly confined to these
      transcription units, and inhibition of transcription by alpha-amanitin resulted
      in the initiation of replication within transcription units, indicating that
      transcription is necessary to limit initiation events to the intergenic region.
      However, the resumption of DHFR transcription after mitosis took place prior to
      the ODP and so is not on its own sufficient to suppress initiation of
      replication. Together, these results demonstrate a remarkable flexibility in
      sequence selection for initiating replication and implicate transcription as one
      important component of origin specification at the ODP.

PMID- 16428459
TI  - Nuclear suppression of mitochondrial defects in cells without the ND6 subunit.
AB  - Previously, we characterized a mouse cell line, 4A, carrying a mitochondrial DNA
      mutation in the subunit for respiratory complex I, NADH dehydrogenase, in the ND6
      gene. This mutation abolished the complex I assembly and disrupted the
      respiratory function of complex I. We now report here that a galactose-resistant
      clone, 4AR, was isolated from the cells carrying the ND6 mutation. 4AR still
      contained the homoplasmic mutation, and apparently there was no ND6 protein
      synthesis, whereas the assembly of other complex I subunits into complex I was
      recovered. Furthermore, the respiratory activity and mitochondrial membrane
      potential were fully recovered. To investigate the genetic origin of this
      compensation, the mitochondrial DNA (mtDNA) from 4AR was transferred to a new
      nuclear background. The transmitochondrial lines failed to grow in galactose
      medium. We further transferred mtDNA with a nonsense mutation at the ND5 gene to
      the 4AR nuclear background, and a suppression for mitochondrial deficiency was
      observed. Our results suggest that change(s) in the expression of a certain
      nucleus-encoded factor(s) can compensate for the absence of the ND6 or ND5
      subunit.

PMID- 16428460
TI  - Oxidative stress-responsive transcription factor ATF3 potentially mediates
      diabetic angiopathy.
AB  - Previous results of our cDNA microarray analysis to look for genes whose
      expression level correlates well with in vitro tubulogenesis by NP31 endothelial
      cells revealed the transcription factor ATF3 known to be responsive to stress
      such as reactive oxygen species (ROS). Anti-ATF3 small interfering RNA gave an
      inhibitory influence on tube formation by NP31 cells expressing an activated form
      of the vascular endothelial growth factor receptor 1 (VEGFR-1) kinase. When
      expression of ATF3 was regulated under the control of tetracycline system in NP31
      cells, they acquired the tubulogenic ability upon ATF3 induction. While ATF3
      failed to induce expressions of VEGF and VEGFR, it regulated those of CDK2, CDK4,
      p8, plasminogen activator inhibitor 1, integrin alpha1, subunit and matrix
      metalloprotease MMP13. In H2O2-stimulated NP31 cells as well as endothelial cells
      of glomerulus and aorta of Otsuka-Long-Evans-Tokushima-Fatty diabetic model rats,
      concomitantly enhanced expressions of ATF3, PAI-1, and p8 were observed. Given
      the proposed hypothesis of the close linkage between diabetic angiopathy and ROS,
      those data suggest that ROS-associated diabetic complication may involve ATF3
      mediated pathological angiogenesis.

PMID- 16428458
TI  - Protection against fatty liver but normal adipogenesis in mice lacking adipose
      differentiation-related protein.
AB  - Adipose differentiation-related protein (ADFP; also known as ADRP or
      adipophilin), is a lipid droplet (LD) protein found in most cells and tissues.
      ADFP expression is strongly induced in cells with increased lipid load. We have
      inactivated the Adfp gene in mice to better understand its role in lipid
      accumulation. The Adfp-deficient mice have unaltered adipose differentiation or
      lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in
      hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To
      determine the mechanism for the reduced hepatic TG content, we measured hepatic
      lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and
      utilization, all of which parameters were shown to be similar between mutant and
      wild-type mice. The finding of similar VLDL output in the presence of a reduction
      in total TG in the Adfp-deficient liver is explained by the retention of TG in
      the microsomes where VLDL is assembled. Given that lipid droplets are thought to
      form from the outer leaflet of the microsomal membrane, the reduction of TG in
      the cytosol with concomitant accumulation of TG in the microsome of Adfp-/- cells
      suggests that ADFP may facilitate the formation of new LDs. In the absence of
      ADFP, impairment of LD formation is associated with the accumulation of
      microsomal TG but a reduction in TG in other subcellular compartments.

PMID- 16428461
TI  - Regulation of replication licensing by acetyltransferase Hbo1.
AB  - The initiation of DNA replication is tightly regulated in eukaryotic cells to
      ensure that the genome is precisely duplicated once and only once per cell cycle.
      This is accomplished by controlling the assembly of a prereplicative complex (pre
      RC) which involves the sequential binding to replication origins of the origin
      recognition complex (ORC), Cdc6/Cdc18, Cdt1, and the minichromosome maintenance
      complex (Mcm2-Mcm7, or Mcm2-7). Several mechanisms of pre-RC regulation are
      known, including ATP utilization, cyclin-dependent kinase levels, protein
      turnover, and Cdt1 binding by geminin. Histone acetylation may also affect the
      initiation of DNA replication, but at present neither the enzymes nor the steps
      involved are known. Here, we show that Hbo1, a member of the MYST histone
      acetyltransferase family, is a previously unrecognized positive regulatory factor
      for pre-RC assembly. When Hbo1 expression was inhibited in human cells, Mcm2-7
      failed to associate with chromatin even though ORC and Cdc6 loading was normal.
      When Xenopus egg extracts were immunodepleted of Xenopus Hbo1 (XHbo1), chromatin
      binding of Mcm2-7 was lost, and DNA replication was abolished. The binding of
      Mcm2-7 to chromatin in XHbo1-depleted extracts could be restored by the addition
      of recombinant Cdt1.

PMID- 16428462
TI  - Respiratory failure due to differentiation arrest and expansion of alveolar cells
      following lung-specific loss of the transcription factor C/EBPalpha in mice.
AB  - The leucine zipper family transcription factor CCAAT enhancer binding protein
      alpha (C/EBPalpha) inhibits proliferation and promotes differentiation in various
      cell types. In this study, we show, using a lung-specific conditional mouse model
      of C/EBPalpha deletion, that loss of C/EBPalpha in the respiratory epithelium
      leads to respiratory failure at birth due to an arrest in the type II alveolar
      cell differentiation program. This differentiation arrest results in the lack of
      type I alveolar cells and differentiated surfactant-secreting type II alveolar
      cells. In addition to showing a block in type II cell differentiation, the
      neonatal lungs display increased numbers of proliferating cells and decreased
      numbers of apoptotic cells, leading to epithelial expansion and loss of airspace.
      Consistent with the phenotype observed, genes associated with alveolar
      maturation, survival, and proliferation were differentially expressed. Taken
      together, these results identify C/EBPalpha as a master regulator of airway
      epithelial maturation and suggest that the loss of C/EBPalpha could also be an
      important event in the multistep process of lung tumorigenesis. Furthermore, this
      study indicates that exploring the C/EBPalpha pathway might have therapeutic
      benefits for patients with respiratory distress syndromes.

PMID- 16428463
TI  - Essential elements of a licensed, mammalian plasmid origin of DNA synthesis.
AB  - We developed a mammalian plasmid replicon with a formerly uncharacterized origin
      of DNA synthesis, 8xRep*. 8xRep* functions efficiently to support once-per-cell
      cycle synthesis of plasmid DNA which initiates within Rep*. By characterizing
      Rep*'s requirements for acting as an origin, we have uncovered several striking
      properties it shares with DS, the only other well-characterized, licensed,
      mammalian plasmid origin of DNA synthesis. Rep* contains a pair of previously
      unrecognized Epstein-Barr nuclear antigen 1 (EBNA1)-binding sites that are both
      necessary and sufficient in cis for its origin activity. These sites have an
      essential 21-bp center-to-center spacing, are bent by EBNA1, and recruit the
      origin recognition complex. The properties shared between DS and Rep* define cis
      and trans characteristics of a mammalian, extrachromosomal replicon. The role of
      EBNA1 likely reflects its evolution from cellular factors involved in the
      assembly of the initiation machinery.

PMID- 16428464
TI  - Complex formation with damage recognition protein Rad14 is essential for
      Saccharomyces cerevisiae Rad1-Rad10 nuclease to perform its function in
      nucleotide excision repair in vivo.
AB  - Nucleotide excision repair (NER) in eukaryotes requires the assembly of a large
      number of protein factors at the lesion site which then coordinate the dual
      incision of the damaged DNA strand. However, the manner by which the different
      protein factors are assembled at the lesion site has remained unclear.
      Previously, we have shown that in the yeast Saccharomyces cerevisiae, NER
      proteins exist as components of different protein subassemblies: the Rad1-Rad10
      nuclease, for example, forms a tight complex with the damage recognition protein
      Rad14, and the complex of Rad1-Rad10-Rad14 can be purified intact from yeast
      cells. As the Rad1-Rad10 nuclease shows no specificity for binding UV lesions in
      DNA, association with Rad14 could provide an effective means for the targeting of
      Rad1-Rad10 nuclease to damage sites in vivo. To test the validity of this idea,
      here we identify two rad1 mutations that render yeast cells as UV sensitive as
      the rad1Delta mutation but which have no effect on the recombination function of
      Rad1. From our genetic and biochemical studies with these rad1 mutations, we
      conclude that the ability of Rad1-Rad10 nuclease to associate in a complex with
      Rad14 is paramount for the targeting of this nuclease to lesion sites in vivo. We
      discuss the implications of these observations for the means by which the
      different NER proteins are assembled at the lesion site.

PMID- 16428465
TI  - Understanding hypoxia-induced gene expression in early development: in vitro and
      in vivo analysis of hypoxia-inducible factor 1-regulated zebra fish insulin-like
      growth factor binding protein 1 gene expression.
AB  - Insulin-like growth factor binding protein 1 (IGFBP-1) is a hypoxia-inducible
      gene that plays an important role in regulating embryonic growth and development
      under hypoxic stress. The molecular mechanisms underlying hypoxia-induced IGFBP-1
      gene expression in the embryonic tissues are not well understood. Here we report
      that the hypoxia-inducible factor 1 (HIF-1) pathway is established in early
      embryogenesis and mediates hypoxia-induced IGFBP-1 expression. Hypoxia increased
      the HIF-1 activity, and HIF-1alpha overexpression or CoCl2 treatment resulted in
      elevated IGFBP-1 expression in zebra fish embryos. Although the zebra fish IGFBP
      1 promoter contains 13 consensus hypoxia response elements (HREs), deletion and
      mutational analysis revealed that only the HRE positioned at -1090/-1086 is
      required for the hypoxia and HIF-1 induction. Further experiments revealed that
      there is an HIF-1 ancillary sequence (HAS) adjacent only to the functional HRE.
      Mutation of this HAS greatly reduced the responsiveness of the IGFBP-1 promoter
      to hypoxia and HIF-1. The HAS does not directly bind to HIF-1 or affect the
      binding of the HRE to HIF-1. The HAS is bound to a nuclear protein(s), and this
      HAS binding activity is reduced by hypoxia. These results suggest that HIF-1
      mediates hypoxia-induced IGFBP-1 gene expression in early development by
      selectively interacting with the -1090/-1086 HRE and its adjacent HAS.

PMID- 16428467
TI  - Ovarian cancer biomarkers in urine.

PMID- 16428466
TI  - Mechanism of polymerase II transcription repression by the histone variant
      macroH2A.
AB  - macroH2A (mH2A) is an unusual histone variant consisting of a histone H2A-like
      domain fused to a large nonhistone region. In this work, we show that histone
      mH2A represses p300- and Gal4-VP16-dependent polymerase II transcription, and we
      have dissected the mechanism by which this repression is realized. The repressive
      effect of mH2A is observed at the level of initiation but not at elongation of
      transcription, and mH2A interferes with p300-dependent histone acetylation. The
      nonhistone region of mH2A is responsible for both the repression of initiation of
      transcription and the inhibition of histone acetylation. In addition, the
      presence of this domain of mH2A within the nucleosome is able to block nucleosome
      remodeling and sliding of the histone octamer to neighboring DNA segments by the
      remodelers SWI/SNF and ACF. These data unambiguously identify mH2A as a strong
      transcriptional repressor and show that the repressive effect of mH2A is realized
      on at least two different transcription activation chromatin-dependent pathways:
      histone acetylation and nucleosome remodeling.

PMID- 16428468
TI  - Targeted modulation of MGMT: clinical implications.
AB  - O(6)-Methylguanine DNA methyltransferase (MGMT) has been studied for >20 years as
      a gene that is associated with the mutagenicity and cytotoxicity induced by
      either methylating carcinogens or alkylating (methylating and chloroethylating)
      therapeutic agents. Pioneering studies of alkylating agents identified alkylated
      guanine at the O(6) position, the substrate of MGMT, as a potentially
      promutagenic and lethal toxic DNA lesion. MGMT plays a prominent role in DNA
      adduct repair that limits the mutagenic and cytotoxic effect of alkylating
      agents. Because of its role in cancer etiology and chemotherapy resistance, MGMT
      is of particular interest. In this article, the clinical effect of MGMT
      expression and targeted modulation of MGMT will be summarized.

PMID- 16428469
TI  - Erythropoietin biology in cancer.
AB  - Erythropoietin (Epo) has long been known to be the principal hematopoietic growth
      factor that regulates cellular proliferation and differentiation along the
      erythroid lineage. Recent studies have shown that Epo is a pleiotropic cytokine
      that is proangiogenic and exerts broad tissue-protective effects in diverse
      nonhematopoietic organs. Recombinant Epo (rEpo) has been widely used in the
      clinic to prevent or treat malignancy-associated anemia. A series of clinical
      trials have documented the efficacy of rEpo in reducing RBC transfusion
      requirements and improving quality of life in cancer patients, and a recent meta
      analysis suggested a positive effect on survival. However, two randomized trials
      reported negative outcomes with rEpo, as patients in the rEpo arm fared worse
      than their placebo-treated counterparts with respect to progression-free
      survival. The expression of Epo receptor (EpoR) in cancer cells has raised the
      possibility that exogenous rEpo may exert direct effects on tumor cells
      associated with the potential for stimulation of proliferation, inhibition of
      apoptosis, or modulation of sensitivity to chemoradiation therapy. The presence
      of an autocrine-paracrine Epo-EpoR system in tumors and potential effects of Epo
      on tumor microenvironment and angiogenesis are consistent with a complex biology
      for Epo-EpoR signaling in cancer that requires further research. This review
      describes Epo and EpoR biology, focusing on the pleiotropic effects of Epo on
      nonhematopoietic tissues as well as the expression and function of EpoR in cancer
      cells.

PMID- 16428470
TI  - Eradication of leukemia stem cells as a new goal of therapy in leukemia.
AB  - Leukemias have traditionally been classified and treated on the basis of
      phenotypic characteristics, such as morphology and cell-surface markers, and,
      more recently, cytogenetic aberrations. These classification systems are flawed
      because they do not take into account cellular function. The leukemia cell
      population is functionally heterogeneous: it consists of leukemia stem cells
      (LSC) and mature leukemia cells that differentiate abnormally to varying extents.
      Like normal hematopoietic stem cells, LSCs are quiescent and have self-renewal
      and clonogenic capacity. Because they are quiescent, LSCs do not respond to cell
      cycle-specific cytotoxic agents used to treat leukemia and so contribute to
      treatment failure. These cells may undergo mutations and epigenetic changes,
      further leading to drug resistance and relapse. Recent data suggest that mature
      leukemia cells may acquire LSC characteristics, thereby evading chemotherapeutic
      treatment and sustaining the disease. Ongoing research is likely to reveal the
      molecular mechanisms responsible for LSC characteristics and lead to novel
      strategies for eradicating leukemia.

PMID- 16428471
TI  - High-resolution genomic profiling reveals association of chromosomal aberrations
      on 1q and 16p with histologic and genetic subgroups of invasive breast cancer.
AB  - PURPOSE: Invasive ductal carcinoma and invasive lobular carcinoma (ILC) represent
      the major histologic subtypes of invasive breast cancer. They differ with regard
      to presentation, metastatic spread, and epidemiologic features. To elucidate the
      genetic basis of these differences, we analyzed copy number imbalances that
      differentiate the histologic subtypes. EXPERIMENTAL DESIGN: High-resolution
      genomic profiling of 40 invasive breast cancers using matrix-comparative genomic
      hybridization with an average resolution of 0.5 Mb was conducted on bacterial
      artificial chromosome microarrays. The data were subjected to classification and
      unsupervised hierarchical cluster analyses. Expression of candidate genes was
      analyzed in tumor samples. RESULTS: The highest discriminating power was achieved
      when combining the aberration patterns of chromosome arms 1q and 16p, which were
      significantly more often gained in ILC. These regions were further narrowed down
      to subregions 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. Located within the
      candidate gains on 1q are two genes, FMO2 and PTGS2, known to be overexpressed in
      ILC relative to invasive ductal carcinoma. Assessment of four candidate genes on
      16p11.2 by real-time quantitative PCR revealed significant overexpression of FUS
      and ITGAX in ILC with 16p copy number gain. Unsupervised hierarchical cluster
      analysis identified three molecular subgroups that are characterized by different
      aberration patterns, in particular concerning gain of MYC (8q24) and the
      identified candidate regions on 1q24.2-25.1, 1q25.3-q31.3, and 16p11.2. These
      genetic subgroups differed with regard to histology, tumor grading, frequency of
      alterations, and estrogen receptor expression. CONCLUSIONS: Molecular profiling
      using bacterial artificial chromosome arrays identified DNA copy number
      imbalances on 1q and 16p as significant classifiers of histologic and molecular
      subgroups.

PMID- 16428472
TI  - Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.
AB  - PURPOSE: The EphA2 receptor tyrosine kinase is believed to play a role in tumor
      growth and metastasis. The clinical significance of the expression of EphA2 was
      observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers.
      The purpose of this work was to determine the expression of EphA2 and its ligand,
      Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine
      EphA2 as a new target for therapy in bladder cancer. EXPERIMENTAL DESIGN: EphA2
      mRNA and protein expression was investigated by reverse transcription-PCR and
      Western blot, respectively, in bladder cancer cell lines. In addition, the
      expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with
      different stages of urinary bladder cancer was determined by
      immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of
      bladder cancer cells was also investigated using an adenoviral delivery system.
      RESULTS: Western blot analysis showed high EphA2 expression in TCCSUP, T24, and
      UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal
      urothelium but increased greatly in advancing stages of urothelial carcinoma (P <
      0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues
      and high in cancerous tissues, but it was similar across the various stages of
      urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in
      urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be
      significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4)
      stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of
      TCCSUP cells. CONCLUSION: EphA2 may serve as a novel target for bladder cancer
      therapy.

PMID- 16428473
TI  - Biological significance of isolated tumor cells and micrometastasis in lymph
      nodes evaluated using a green fluorescent protein-tagged human gastric cancer
      cell line.
AB  - PURPOSE: The biological significance of isolated tumor cells and micrometastasis
      in lymph node defined by the International Union against Cancer remains
      essentially unknown because of the lack of appropriate animal models. In the
      present study, we developed a lymph node micrometastasis model featuring a human
      gastric cancer cell line tagged with green fluorescent protein gene (GCIY-EGFP),
      which allows visualization of even isolated tumor cells in the development of
      metastasis without histologic procedure. Using this model, we investigated the
      effect of surgery and chemotherapy on the growth of early-phase metastasis
      formation in the lymph nodes. EXPERIMENTAL DESIGN: The time course of spontaneous
      inguinal lymph node metastasis after s.c. inoculation of GCIY-EGFP cells into
      nude mice was examined with fluorescence dissecting microscopy. Then, the effects
      of surgical removal of the primary tumor with or without anti-asialo GM1
      treatment or postoperative chemotherapy on the growth of isolated tumor cells and
      micrometastasis in the lymph nodes were examined. RESULTS: GCIY-EGFP cells were
      found to metastasize spontaneously to the inguinal lymph nodes to form isolated
      tumor cells, micrometastasis, and, finally, develop macroscopic metastasis at 1
      to 2, 3 to 5, and 5 weeks postinjection, respectively. When the primary tumors
      were removed within 2 weeks of inoculation, isolated tumor cells, but not
      micrometastasis, in the lymph nodes regressed by 4 weeks after surgery in all the
      mice examined (five of five). This spontaneous regression of isolated tumor cells
      was completely reversed by anti-asialo GM1 treatment, which could deplete natural
      killer cells effectively in nude mice. Chemotherapy following resection of the
      primary tumor at an early stage partially eliminated the remaining
      micrometastasis in the lymph nodes. CONCLUSIONS: These results suggest that
      isolated tumor cells in the regional lymph nodes regressed by removal of the
      primary tumor mainly via natural killer cell-mediated antitumor activity and that
      micrometastasis in the lymph nodes could be effectively eliminated by the
      postoperative chemotherapy.

PMID- 16428474
TI  - Stress hormone-mediated invasion of ovarian cancer cells.
AB  - PURPOSE: There is growing evidence that stress and other behavioral factors may
      affect cancer progression and patient survival. The underlying mechanisms for
      this association are poorly understood. The purpose of this study is to determine
      the effects of stress-associated hormones norepinephrine, epinephrine, and
      cortisol on the invasive potential of ovarian cancer cells. EXPERIMENTAL DESIGN:
      The ovarian cancer cells EG, SKOV3, and 222 were exposed to increasing levels of
      either norepinephrine, epinephrine, or cortisol, and the in vitro invasive
      potential was determined using the membrane invasion culture system.
      Additionally, the effects of these stress hormones on matrix metalloproteinase-2
      (MMP-2) and MMP-9 were determined by ELISA. The effects of the beta-adrenergic
      agonist isoproterenol on in vivo tumor growth were determined using nude mice.
      RESULTS: Stress levels of norepinephrine increased the in vitro invasiveness of
      ovarian cancer cells by 89% to 198%. Epinephrine also induced significant
      increases in invasion in all three cell lines ranging from 64% to 76%. Cortisol
      did not significantly affect invasiveness of the EG and 222 cell lines but
      increased invasion in the SKOV3 cell line (P = 0.01). We have previously shown
      that ovarian cancer cells express beta-adrenergic receptors. The beta-adrenergic
      antagonist propanolol (1 mumol/L) completely blocked the norepinephrine-induced
      increase in invasiveness. Norepinephrine also increased tumor cell expression of
      MMP-2 (P = 0.02 for both SKOV3 and EG cells) and MMP-9 (P = 0.01 and 0.04,
      respectively), and pharmacologic blockade of MMPs abrogated the effects of
      norepinephrine on tumor cell invasive potential. Isoproterenol treatment resulted
      in a significant increase in tumor volume and infiltration in the SKOV3ip1 in
      vivo model, which was blocked by propranolol. CONCLUSIONS: These findings provide
      direct experimental evidence that stress hormones can enhance the invasive
      potential of ovarian cancer cells. These effects are most likely mediated by
      stimulation of MMPs.

PMID- 16428475
TI  - Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma.
AB  - PURPOSE: Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing Th2 T
      cells. Clonal T cells and CTCL skin lesions typically express Th2 cytokines,
      including interleukin (IL)-4, IL-5, and IL-10, but fail to produce Th1 cytokines.
      However, the reason for Th2 bias is unknown. IL-18 is a pleiotropic
      proinflammatory cytokine produced by monocytes/macrophages lineage as well as
      epithelial cells, such as human keratinocytes. In the absence of IL-12, IL-18
      leads to increased immunoglobulin E production from B cells and enhanced
      production of IL-4 and IL-13 by basophils, mast cells, and CD4(+) T cells. We
      have analyzed cytokines in CTCL patients, which may bias the immune response
      around the Th1/Th2 axis. EXPERIMENTAL DESIGN: We examined plasma of 95 CTCL
      patients and skin of 20 CTCL patients for IL-18, caspase-1, IL-12, and other
      cytokines. To identify the presence or absence of these cytokine proteins in CTCL
      and normal skin, we cultured explants from skin biopsies on three-dimensional
      matrices. RESULTS: Plasma levels of IL-18 and its converting enzyme, caspase-1,
      were significantly elevated in CTCL. mRNA levels for these factors were also
      elevated in CTCL skin lesions. Matrices populated with CTCL lesional skin
      produced significant amounts of IL-18 and caspase-1; however, production of IL-12
      protein was barely detectable. CONCLUSIONS: We propose that the high levels of IL
      18 expression in lesional CTCL skin contribute to increased plasma levels of IL
      18 and that this, in the face of significantly lower levels of IL-12, may
      contribute to the Th2 bias seen in this disease.

PMID- 16428476
TI  - Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in
      bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway.
AB  - PURPOSE: Aberrant activation of the Wingless-type (Wnt) pathway plays a
      significant role in the pathogenesis of several human cancers. Wnt inhibitory
      factor-1 (Wif-1) was identified as one of the secreted antagonists that can bind
      Wnt protein. We hypothesize that Wif-1 plays an important role in bladder cancer
      pathogenesis. EXPERIMENTAL DESIGN: To test this hypothesis, epigenetic and
      genetic pathways involved in the Wif-1 gene modulation and expression of Wnt/beta
      catenin-related genes were analyzed in 4 bladder tumor cell lines and 54 bladder
      tumor and matched normal bladder mucosa. RESULTS: Wif-1 mRNA expression was
      significantly enhanced after 5-aza-2'-deoxycytidine treatment in bladder tumor
      cell lines. Wif-1 promoter methylation level was significantly higher and Wif-1
      mRNA expression was significantly lower in bladder tumor samples than in bladder
      mucosa samples. In the total bladder tumor and bladder mucosa samples, an inverse
      correlation was found between promoter methylation and Wif-1 mRNA transcript
      levels. However, loss-of-heterozygosity at chromosome 12q14.3 close to the Wif-1
      gene loci was a rare event (3.7%). Nuclear accumulation of beta-catenin was
      significantly more frequent in bladder tumor than in bladder mucosa and inversely
      correlated with Wif-1 expression. In addition, known targets of the canonical
      Wnt/beta-catenin signaling pathway, such as c-myc and cyclin D1, were up
      regulated in bladder tumor compared with bladder mucosa, and this up-regulation
      was associated with reduced Wif-1 expression at both mRNA and protein levels.
      Furthermore, transfection of Wif-1 small interfering RNA into bladder tumor cells
      expressing Wif-1 mRNA transcripts had increased levels of c-myc and cyclin D1 and
      accelerated cell growth. CONCLUSION: This is the first report showing that CpG
      hypermethylation of the Wif-1 promoter is a frequent event in bladder tumor and
      may contribute to pathogenesis of bladder cancer through aberrant canonical
      Wnt/beta-catenin signaling pathway. The present study elucidates novel pathways
      that are involved in the pathogenesis of bladder cancer.

PMID- 16428477
TI  - Int7G24A variant of transforming growth factor-beta receptor type I is associated
      with invasive breast cancer.
AB  - PURPOSE: The transforming growth factor-beta (TGF-beta) signaling pathway has
      been frequently implicated in breast cancer. An intronic variant (Int7G24A) of
      TGF-beta receptor type I (TGFBR1) is associated with kidney and bladder cancers
      in our recent study. We hypothesize that this germline variant may be involved in
      development and progression of breast cancer. EXPERIMENTAL DESIGN: Case-control
      studies were designed from archived paraffin-embedded tissue specimens from the
      same geographic area with a homogenous ethnic population. We analyzed 223
      patients (25 with preinvasive tumors and 198 with invasive and metastatic breast
      cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP.
      Another germline deletion (TGFBR1*6A) and somatic mutations in the TGFBR1 were
      also analyzed by PCR and single-strand conformational polymorphism. RESULTS: The
      Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48%
      of patients with invasive breast cancers compared with 26% controls (P =
      0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in
      patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers
      were found in the control group. The TGFBR1*6A allele was not significantly
      associated with breast cancer patients and only one somatic mutation was found in
      71 breast cancers. CONCLUSION: These data suggest that the germline Int7G24A
      variant may represent a risk factor for invasive breast cancer and a marker for
      breast cancer progression. A separate study with a larger sample size is
      warranted to validate the association of the Int7G24A with human breast cancer.

PMID- 16428478
TI  - Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and
      identification of SSX-4 epitopes recognized by CD4+ T cells.
AB  - PURPOSE: Synovial sarcoma X (SSX) breakpoint genes are expressed in a variety of
      cancers but not in normal tissues, except for testis, and are potential targets
      for immunotherapy. The aims of this study were to determine the expression and
      immunogenicity of these antigens in patients with epithelial ovarian cancer
      (EOC). EXPERIMENTAL DESIGN: SSX-1-, SSX-2-, and SSX-4-specific reverse
      transcription-PCR were done on a panel of EOC specimens. Sera from a subgroup of
      the patients were tested for SSX-2 and SSX-4 antibody by ELISA and recombinant
      antigen expression on yeast surface (RAYS). In vitro stimulation of peripheral
      blood mononuclear cells from a patient bearing SSX-4-expressing tumor with a pool
      of long peptides spanning the protein sequence was used for assessment of SSX-4
      specific CD4(+) T cells recognizing distinct antigenic sequences restricted by
      HLA class II alleles. RESULTS: Our results indicate expression of SSX-1, SSX-2,
      and SSX-4 in 2.5%, 10%, and 16% of 120 EOC specimens, respectively. When all
      three SSX antigens are considered, aberrant expression was found in 26% of
      ovarian tumors. Antibodies to SSX-2 and SSX-4 were detectable by ELISA and RAYS
      in two patients. SSX-4-specific CD4(+) T cells recognizing two previously
      undescribed SSX-4-derived T-cell epitopes in association with HLA-DR (SSX-4: 51
      70 and SSX-4: 61-180) were identified. CONCLUSIONS: Our study shows aberrant
      expression of SSX antigens in a proportion of patients with EOC. The evidence of
      humoral immunity to SSX-2 and SSX-4, and SSX-4-specific CD4(+) T cells among
      circulating lymphocytes in patients with antigen expressing EOC suggest that
      these antigens are attractive targets for specific immunotherapy in EOC.

PMID- 16428479
TI  - Increased expression of mitotic checkpoint genes in breast cancer cells with
      chromosomal instability.
AB  - PURPOSE: Most breast cancers have chromosomal instability that seems related to
      defective mitotic spindle checkpoints. Because the molecular basis of this defect
      is unknown, we evaluated breast cancer cell lines and tissues for possible
      defects involving the major mitotic checkpoint genes responsible for maintaining
      chromosomal stability. EXPERIMENTAL DESIGN: We analyzed sequences and expression
      levels (RNA and protein) of eight major spindle checkpoint genes (MAD1L1, MAD2L1,
      MAD2L2, BUB1, BUB1B, BUB3, CDC20, and TTK) in a panel of 12 breast cancer cell
      lines, most with established genetic instability and defective spindle damage
      checkpoint response. mRNA levels of these genes were also measured in primary
      tumor samples, and immunohistochemical staining was used to evaluate BUB1B
      protein levels in a panel of 270 additional cases of breast cancer. RESULTS: No
      functionally significant sequence variations were found for any of the eight
      genes in the breast cancer cell lines with chromosomal instability. More
      surprisingly, the mRNA and protein levels for these checkpoint genes are
      significantly higher in the genetically unstable breast cancer cell lines and in
      high-grade primary breast cancer tissues than in the stable (and checkpoint
      proficient) MCF-10A and normal mammary epithelial cells, or in normal breast
      tissues. In fact, overexpression of the BUB1B protein is a marker that recognizes
      nearly 80% of breast cancers in paraffin-embedded tissues. CONCLUSIONS: Defective
      mitotic spindle checkpoints in breast cancer are most likely not caused by low
      expression or mutations of these eight checkpoint genes. High levels of these
      particular transcripts could represent a cellular compensation for defects in
      other molecular components of the mitotic spindle damage checkpoint, and
      increased expression of these genes might be markers of breast cancers with
      chromosomal instability.

PMID- 16428480
TI  - Tumor-associated antigen recognized by the 22-1-1 monoclonal antibody encourages
      colorectal cancer progression under the scanty CD8+ T cells.
AB  - PURPOSE: The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a
      novel tumor-associated antigen. Although evidence suggests that RCAS1 suppresses
      immunity by inducing tumor-infiltrating lymphocyte (TIL) apoptosis, RCAS1
      function in humans is controversial. RCAS1 overexpression leads to the generation
      of the Tn glycan antigen (N-acetyl-D-galactosamine, GalNAc) recognized by the 22
      1-1 monoclonal antibody. The objective of this study is to examine Tn glycan
      antigen function in colorectal cancer and to determine its relationship to CD8+ T
      cells and prognosis. EXPERIMENTAL DESIGN: Immunohistochemical analyses examined
      Tn expression in tumor cells and CD8 on TILs in 146 surgically resected
      colorectal cancer. RESULTS: Of 146 samples, 68 tumors (47%) were Tn+; 72 tumors
      (49%) were CD8+. Using Cox multivariate analysis and the Kaplan-Meier method, Tn
      and CD8 positivity were determined to be mutually independent prognostic factors
      (P = 0.0266 and 0.0210, respectively). Tn+ patients with CD8+ TILs exhibited
      better survival than Tn+/CD8- patients (P = 0.0129). For CD8- patients, Tn
      positivity was associated with decreased survival from that seen in Tn- patients
      (P = 0.0097), suggesting that Tn exerts a function independent of CD8+ T cells in
      tumor progression. In all patients and cases with synchronous liver metastases (n
      = 29), the Tn+/CD8- survival rate was significantly lower than that seen for
      other groups (P = 0.0001 and 0.0063, respectively). The average number of liver
      metastases in Tn+/CD8- cases also increased (mean, 8.2 tumors; P = 0.0032).
      Multivariate analysis identified Tn+/CD8- status and Dukes' staging as
      independent prognostic factors (P = 0.0016 and < 0.0001, respectively).
      CONCLUSIONS: Tn may encourage invasion and innidiation through a mechanism
      independent of CD8+ T cells. Thus, Tn+/CD8- status is a risk factor for multiple
      liver metastases development and an independent negative prognostic factor for
      colorectal cancer.

PMID- 16428481
TI  - Identification of early-stage colorectal cancer patients at risk of relapse post
      resection by immunobead reverse transcription-PCR analysis of peritoneal lavage
      fluid for malignant cells.
AB  - PURPOSE: Colorectal cancer patients diagnosed with stage I or II disease are not
      routinely offered adjuvant chemotherapy following resection of the primary tumor.
      However, up to 10% of stage I and 30% of stage II patients relapse within 5 years
      of surgery from recurrent or metastatic disease. The aim of this study was to
      determine if tumor-associated markers could detect disseminated malignant cells
      and so identify a subgroup of patients with early-stage colorectal cancer that
      were at risk of relapse. EXPERIMENTAL DESIGN: We recruited consecutive patients
      undergoing curative resection for early-stage colorectal cancer. Immunobead
      reverse transcription-PCR of five tumor-associated markers (carcinoembryonic
      antigen, laminin gamma2, ephrin B4, matrilysin, and cytokeratin 20) was used to
      detect the presence of colon tumor cells in peripheral blood and within the
      peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic
      variables were tested for their effect on survival outcomes in univariate
      analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards
      regression analysis was done to determine whether detection of tumor cells was an
      independent prognostic marker for disease relapse. RESULTS: Overall, 41 of 125
      (32.8%) early-stage patients were positive for disseminated tumor cells. Patients
      who were marker positive for disseminated cells in post-resection lavage samples
      showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence
      interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors.
      CONCLUSION: The markers used in this study identified a subgroup of early-stage
      patients at increased risk of relapse post-resection for primary colorectal
      cancer. This method may be considered as a new diagnostic tool to improve the
      staging and management of colorectal cancer.

PMID- 16428482
TI  - p95HER-2 predicts worse outcome in patients with HER-2-positive breast cancer.
AB  - BACKGROUND: The HER-2 receptor undergoes a proteolytic cleavage generating an
      NH(2)-terminally truncated fragment, p95HER-2, that is membrane-associated and
      tyrosine-phosphorylated. We have reported that p95HER-2, but not the full-length
      receptor, p185HER-2, correlated with the extent of lymph node involvement in
      patients with breast cancer and its expression was significantly enhanced in
      nodal metastatic tissue. These facts suggested an important role for p95HER-2
      either as a marker or cause of metastasis and poor outcome in breast cancer. In
      this work, we have studied the prognostic value of p95HER-2 in breast cancer.
      METHODS: Primary breast tumor tissues (n = 483) were from surgical resections
      conducted in hospitals in two different countries: the U.S. (n = 334) and Spain
      (n = 149). HER-2 protein forms, including p185HER-2 and p95HER-2, were examined
      in extracts of primary breast tumors by Western blot analysis. The levels of the
      two forms (high or low) were tested for association with other clinicopathologic
      factors and for correlation with disease-free survival. RESULTS: The median
      follow-up was 46 months. A high level of p95HER-2 in primary tumor tissue
      correlated with reduced 5-year disease-free survival (hazard ratio, 2.55; 95%
      confidence interval, 2.13-8.01; P < 0.0001). The median time for disease-free
      survival was 32 versus 139 months in patients with low levels of p95HER-2. In
      comparison, high levels of the full-length p185HER-2 did not significantly
      correlate with poor outcome (P > 0.1). Multivariate analysis revealed that high
      p95HER-2 was an independent predictor of disease-free survival (hazard ratio,
      1.59; 95% confidence interval, 1.246-1.990; P = 0.0004). CONCLUSIONS: p95HER-2
      expression is an independent prognostic factor in breast cancer and defines a
      group of patients with HER-2-positive breast cancer with significantly worse
      outcome.

PMID- 16428483
TI  - Proteomic-based discovery and characterization of glycosylated eosinophil-derived
      neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine.
AB  - PURPOSE: The objective was to identify and characterize low molecular weight
      proteins/peptides in urine and their posttranslational modifications that might
      be used as a screening tool for ovarian cancer. EXPERIMENTAL DESIGN: Urine
      samples collected preoperatively from postmenopausal women with ovarian cancer
      and benign conditions and from nonsurgical controls were analyzed by surface
      enhanced laser desorption/ionization mass spectrometry and two-dimensional gel
      electrophoresis. Selected proteins from mass profiles were purified by
      chromatography and followed by liquid chromatography-tandem mass spectrometry
      sequence analysis. Specific antibodies were generated for further
      characterization, including immunoprecipitation and glycosylation. Quantitative
      and semiquantitative ELISAs were developed for preliminary validation in patients
      of 128 ovarian cancer, 52 benign conditions, 44 other cancers, and 188 healthy
      controls. RESULTS: A protein (m/z approximately 17,400) with higher peak
      intensities in cancer patients than in benign conditions and controls was
      identified and subsequently defined as eosinophil-derived neurotoxin (EDN). A
      glycosylated form of EDN was specifically elevated in ovarian cancer patients. A
      cluster of COOH-terminal osteopontin was identified from two-dimensional gels of
      urine from cancer patients. Modified forms EDN and osteopontin fragments were
      elevated in early-stage ovarian cancers and a combination of both resulted to 93%
      specificity and 72% sensitivity. CONCLUSIONS: Specific elevated
      posttranslationally modified urinary EDN and osteopontin COOH-terminal fragments
      in ovarian cancer might lead to potential noninvasive screening tests for early
      diagnosis. Urine with less complexity than serum and relatively high
      thermodynamic stability of peptides or metabolites is a promising study medium
      for discovery of the novel biomarkers which may present in many non-urinary tract
      neoplastic diseases.

PMID- 16428484
TI  - Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage
      inhibitory cytokine 1 versus CA19-9.
AB  - PURPOSE: More accurate serum markers of pancreatic cancer could improve the early
      detection and prognosis of this deadly disease. We compared the diagnostic
      utility of a panel of candidate serum markers of pancreatic cancer. EXPERIMENTAL
      DESIGN: We collected preoperative serum from 50 patients with resectable
      pancreatic adenocarcinoma, as well as sera from 50 patients with chronic
      pancreatitis and 50 age/sex-matched healthy controls from our institution. Sera
      were analyzed for the following candidate markers of pancreatic cancer: CA19-9,
      macrophage inhibitory cytokine 1 (MIC-1), osteopontin, tissue inhibitor of
      metalloproteinase 1, and hepatocarcinoma-intestine-pancreas protein levels.
      RESULTS: By logistic regression analysis, MIC-1 and CA19-9 were significant
      independent predictors of diagnosis. Receiver operating characteristic curve
      analysis showed that MIC-1 was significantly better than CA19-9 in
      differentiating patients with pancreatic cancer from healthy controls (area under
      the curve is 0.99 and 0.78, respectively; P = 0.003), but not in distinguishing
      pancreatic cancer from chronic pancreatitis (area under the curve of 0.81 and
      0.74, respectively; P = 0.63). Hepatocarcinoma-intestine-pancreas/pancreatitis
      associated protein, osteopontin, and tissue inhibitor of metalloproteinase 1
      serum levels did not provide additional diagnostic power. CONCLUSION: In the
      differentiation of patients with resectable pancreatic cancer from controls,
      serum MIC-1 outperforms other markers including CA19-9.

PMID- 16428485
TI  - Detection and quantitation of serum mesothelin, a tumor marker for patients with
      mesothelioma and ovarian cancer.
AB  - PURPOSE: To determine whether mesothelin, a cell surface protein highly expressed
      in mesothelioma and ovarian cancer, is shed into serum and if so to accurately
      measure it. EXPERIMENTAL DESIGN: We developed a sandwich ELISA using antibodies
      reacting with two different epitopes on human mesothelin. To quantitate serum
      mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion
      protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56
      patients with mesothelioma, and 21 patients with ovarian cancer were analyzed.
      Serum mesothelin levels were also measured before and after surgical
      cytoreduction in six patients with peritoneal mesothelioma. RESULTS: Elevated
      serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma
      and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were
      increased in 80% and 75% of the cases of mesothelioma and ovarian cancer,
      respectively, in which the tumors expressed mesothelin by immunohistochemistry.
      Out of the six patients with peritoneal mesothelioma who underwent surgery, four
      had elevated serum mesothelin levels before surgery. Out of these four patients,
      three had cytoreductive surgery and the serum mesothelin level decreased by 71%
      on postoperative day 1 and was undetectable by postoperative day 7. CONCLUSIONS:
      We developed a serum mesothelin assay that shows that mesothelin is elevated in
      patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin
      levels after surgery in patients with peritoneal mesothelioma suggests that serum
      mesothelin may be a useful test to monitor treatment response in mesothelin
      expressing cancers.

PMID- 16428486
TI  - Detection of mononucleotide repeat sequence alterations in a large background of
      normal DNA for screening high-frequency microsatellite instability cancers.
AB  - PURPOSE: Mutations in mononucleotide repeat sequence (MRS) are good indicators of
      high-frequency microsatellite instability (MSI-H) cancers, but it has been a
      challenge to detect such mutations in a large background of wild-type DNA; as in
      this setting, PCR errors often generate false positive mutant alleles. In this
      study, we developed a general strategy, referred to as probe clamping primer
      extension-PCR (PCPE-PCR), to detect MRS alterations in a large background of wild
      type DNA. EXPERIMENTAL DESIGN: In PCPE-PCR, genomic DNA is first subjected to
      PCPE, in which mutant single-strand DNA molecules are preferentially produced.
      Next, genomic DNA is removed to enrich for the mutant DNA fraction. Thereafter,
      PCR is carried out using the remaining single-strand DNA molecules as templates.
      Finally, the PCR products are analyzed to reveal the MSI-H status. In this study,
      the sensitivity of this new method was first examined by spiking mutant DNA into
      wild-type DNA at specific ratios followed by studying whether this method is
      applicable to fecal DNA testing. RESULTS: We showed that PCPE-PCR could detect
      both mutated BAT26 and transforming growth factor-beta-RII (A)10 markers in the
      presence of 500-fold excess of normal DNA and that as few as three copies of
      mutated DNA could be detected. In addition, we showed that this technology could
      detect MSI-H colorectal cancer by fecal DNA analysis. CONCLUSION: PCPE-PCR is
      sensitive. In addition, PCPE-PCR is simple and amendable to a cost-effective and
      high-throughput screening operation. This technology may be applicable to
      noninvasive screening of MSI-H cancer.

PMID- 16428487
TI  - Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's
      lymphoma.
AB  - PURPOSE: Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells
      of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and
      quantitation of EBV viral DNA could potentially be used as a biomarker of disease
      activity. EXPERIMENTAL DESIGN: Initially, EBV-DNA viral load was prospectively
      monitored from peripheral blood mononuclear cells (PBMC) in patients with HL.
      Subsequently, we analyzed viral load in plasma from a second cohort of patients.
      A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long
      term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples
      were analyzed. RESULTS: EBV-DNA was detectable in the plasma of all EBV-positive
      patients with HL prior to therapy. However, viral DNA was undetectable following
      therapy in responding patients (P = 0.0156), EBV-positive HL patients in long
      term remission (P = 0.0011), and in all patients with EBV-negative HL (P =
      0.0238). Conversely, there was no association seen for the EBV-DNA load measured
      from PBMC in patients with active EBV-positive HL patients as compared with EBV
      negative HL, or patients in long-term remission. EBV-DNA load in matched
      plasma/PBMC samples were not correlated. CONCLUSIONS: We show that free plasma
      EBV-DNA has excellent sensitivity and specificity, and can be used as a
      noninvasive biomarker for EBV-positive HL and that serial monitoring could
      predict response to therapy. Additional prospective studies are required to
      further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring
      response to treatment in patients with EBV-positive HL.

PMID- 16428488
TI  - Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and
      neck cancers.
AB  - PURPOSE: CD4(+) T cells play a central role in initiating and maintaining
      anticancer immune responses. However, regulatory CD4(+)CD25(+) T cells which
      express Foxp3 have also been shown to inhibit antitumor effector T cells. In view
      of these heterogeneous CD4(+) T-cell populations, this study was designed to
      determine the prognostic value of various tumor-infiltrating CD4(+) T-cell
      populations in head and neck squamous cell carcinoma. EXPERIMENTAL DESIGN: Eighty
      four newly diagnosed untreated patients with histologically proven primary head
      and neck squamous cell carcinoma were included in this study. Double or triple
      immunofluorescence staining was done to assess and quantify the activated
      CD4(+)CD69(+) T cells, regulatory CD4(+)Foxp3(+) T cells, and mixed CD4(+)CD25(+)
      T cells comprising both activated and regulatory T cells. RESULTS: On univariate
      analysis, high levels of tumor-infiltrating CD4(+)CD69(+) T cells were correlated
      with both better locoregional control (P = 0.01) and longer survival (P = 0.01).
      Infiltration by regulatory Foxp3(+)CD4(+) T cells was positively associated with
      a better locoregional control of the tumor. Multivariate analysis showed that the
      only significant prognostic factors related to locoregional control were T stage
      (P = 0.02) and CD4(+)Foxp3(+) T-cell infiltration of the tumor (P = 0.02). In the
      Cox multivariate analysis, only two variables influenced overall survival
      probability: T stage (P = 0.036) and CD4(+)CD69(+) T-cell infiltration (P =
      0.017). CONCLUSION: This study shows that tumor-infiltrating activated
      CD4(+)CD69(+) T cells are associated with a good prognosis in head and neck
      squamous cell carcinoma. In addition, regulatory Foxp3(+)CD4(+) T cells are
      positively correlated with locoregional control may be through down-regulation of
      harmful inflammatory reaction, which could favor tumor progression.

PMID- 16428489
TI  - Expression of carbonic anhydrase IX in astrocytic tumors predicts poor prognosis.
AB  - PURPOSE: Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme, which is
      associated with neoplastic growth. Ectopic CA IX expression has been observed in
      several tumors, whose normal counterparts do not express this enzyme. Normal
      human brain tissue shows only slight or no expression of CA IX. EXPERIMENTAL
      DESIGN: We describe CA IX expression in human diffusely infiltrating
      astrocytomas. The association of CA IX is evaluated with clinicopathologic and
      molecular factors including cell proliferation and apoptosis as well as the
      expression of p53 and epidermal growth factor receptor. RESULTS: CA IX
      immunopositivity was observed in 284 cases of 362 (78%) tumors. The positive
      areas were often located in close proximity to necrotic regions (P < 0.001). The
      CA IX immunoreactivity showed strong association with tumor malignancy grades (P
      < 0.0001). CA IX showed no association with p53 expression nor did it correlate
      with epidermal growth factor receptor-amplification, apoptosis, or cell
      proliferation. CA IX intensity had significant prognostic value in univariate
      (P=0.0011, log-rank test) and multivariate survival analysis (P = 0.038, Cox
      analysis). CONCLUSIONS: CA IX expression is common in diffusely infiltrating high
      grade astrocytomas. Our results suggest that CA IX is a useful biomarker for
      predicting poor prognosis of astrocytic tumors. It may also be a promising target
      molecule for the improvement of therapeutic interventions in astrocytomas.

PMID- 16428490
TI  - Correlations between serum monocyte chemotactic protein-1 levels, clinical
      prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer
      patients.
AB  - PURPOSE: We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast
      cancer patients in relationship to their clinicopathologic variables and immune
      response to a /neu E75 vaccine. EXPERIMENTAL DESIGN: We measured MCP-1 levels in
      32 /neu(+) breast cancer patients before and after vaccination with a /neu E75
      peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical
      prognostic variables were collected. Vaccine-specific immunologic responses were
      monitored. RESULTS: Serum MCP-1 levels >250 pg/mL (MCP-high) correlated with
      favorable prognostic variables. MCP-high patients compared with MCP-low (<250
      pg/mL) patients showed statistically significant later onset of disease, earlier
      stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high
      patients had increased levels of preexisting immunity when compared with MCP-low
      patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher
      inducible levels of MCP-1 compared with MCP-high patients (median increase, 41%
      versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with >50%
      increase in MCP-1 levels (response-high) had worse clinical prognostic variables
      compared with patients with <50% increase (response-low). Response-high patients
      had statistically significant more poorly differentiated tumors, later stage of
      disease, and higher percentage of large tumors. Patients with >30%
      postvaccination MCP-1 increase also showed significant increases in E75-specific
      CD8(+) T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination.
      CONCLUSIONS: High serum MCP-1 levels in breast cancer patients correlate with
      favorable prognostic variables and increased preexisting /neu immunity. E75
      vaccination induces the largest MCP-1 response in patients with unfavorable
      clinicopathologic variables. Therefore, low serum MCP-1 levels may identify
      patients with worse prognosis and those most likely to benefit from this
      vaccination.

PMID- 16428491
TI  - Skp2 overexpression is highly representative of intrinsic biological
      aggressiveness and independently associated with poor prognosis in primary
      localized myxofibrosarcomas.
AB  - PURPOSE: Two SCF(Skp2) ubiquitin ligase-related proteins, Skp2 and cyclin
      dependent kinase subunit 1 (Cks1), are involved in posttranscriptional
      degradation of p27(Kip1) tumor suppressor. We analyzed the prognostic utility of
      p27(Kip1) and its interacting cell cycle regulators in myxofibrosarcomas.
      EXPERIMENTAL DESIGN: Clinicopathologic features and tissue microarray-based
      immunohistochemical expression of p27(Kip1), Skp2, Cks1, cyclin E, cyclin A, Ki
      67, and minichromosome maintenance protein 2 (Mcm2) were assessed in 70 primary
      myxofibrosarcomas and correlated with clinical outcomes. Skp2 mRNA expression and
      the relationship between Skp2 and p27(Kip1) proteins were examined in six cases
      by semiquantitative reverse transcription-PCR and Western blotting, respectively.
      RESULTS: High indices of Skp2 (> or =10%), cyclin A (> or =10%), and Mcm2 (> or
      =50%) were adverse prognosticators at the univariate level. Furthermore, co
      overexpression of Skp2 and cyclin A identified highly lethal cases in the entire
      cohort [P < 0.0001 for disease-specific survival (DSS), P = 0.0004 for overall
      survival (OS)] and the lower-grade subset (Federation Nationale des Centres de
      Lutte Contre le Cancer grade 1 and 2; P = 0.0006 for DSS, P = 0.0093 for OS). In
      multivariate analyses, Skp2 overexpression overshadowed most intrinsic
      clinicopathologic factors and independently correlated with worse metastasis-free
      survival (P = 0.0012), DSS (P = 0.0234), and OS (P = 0.0056). Notably, positive
      margins independently predicted inferior local recurrence-free survival (P =
      0.0012) and also negatively affected metastasis-free survival (P = 0.0471), DSS
      (P = 0.0152), and OS (P = 0.0173). Reverse transcription-PCR showed up-regulation
      of Skp2 mRNA in four cases and Western blotting displayed a matched expression
      pattern of Skp2. CONCLUSIONS: Margin status and intrinsic property of
      myxofibrosarcomas both affect patient survival. Skp2 overexpression is highly
      representative of the biological aggressiveness of myxofibrosarcomas and plays an
      important prognostic role.

PMID- 16428493
TI  - Increased NBS1 expression is a marker of aggressive head and neck cancer and
      overexpression of NBS1 contributes to transformation.
AB  - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most
      frequent type of cancer worldwide. However, the molecular genetic alterations
      underlying its malignant behavior and progression are little known. We showed
      previously that c-MYC directly activates the expression of the DNA double-strand
      break repair gene NBS1, and NBS1 overexpression contributes to transformation.
      Here, we investigate the role of NBS1 overexpression in HNSCC. EXPERIMENTAL
      DESIGN: Immunohistochemistry analysis of NBS1 expression was done in 81 locally
      advanced HNSCC patients. Real-time PCR and Western blot analysis were used to
      confirm immunohistochemistry results. Human hypopharyngeal cancer cell lines
      (FADU) with overexpressing NBS1 (FADUNBS) or inducible short interference RNA to
      repress endogenous NBS1 (FADUNBSi) were generated by stable transfection. Soft
      agar clonogenicity assay was used to determine the transformation activity.
      Western blot analysis and phosphatidylinositol 3-kinase (PI3K) assay were done to
      evaluate the signaling pathways that were involved. RESULTS: NBS1 overexpression
      was identified in 45% of advanced HNSCC patients. It was an independent marker of
      poor prognosis. NBS1 expression levels correlated with the transformation
      activity of FADU clones and also correlated with the phosphorylation levels of
      Akt and its downstream target mammalian target of rapamycin (mTOR). PI3K activity
      was increased in NBS1-overexpressing FADU clones. NBS1 overexpression also
      correlated with increased Akt phosphorylation levels in tumor samples.
      CONCLUSIONS: Increased NBS1 expression is a significant prognostic marker of
      advanced HNSCC, and the underlying mechanism may involve the activation of the
      PI3K/Akt pathway.

PMID- 16428492
TI  - Sex-specific survival advantage with parathyroid hormone-related protein in non
      small cell lung carcinoma patients.
AB  - PURPOSE: Parathyroid hormone-related protein (PTHrP) is commonly expressed in non
      small cell lung carcinomas (NSCLC). Expression of the protein could have
      implications for progression of the disease because it regulates cancer cell
      growth, apoptosis, and angiogenesis. However, its relationship with survival has
      not been evaluated in a large-scale investigation. EXPERIMENTAL DESIGN: PTHrP
      expression was assessed in paraffin-embedded tumor samples from 407 patients with
      NSCLC by immunohistochemistry. A pathologist unaware of the clinical history
      classified specimens as PTHrP positive or PTHrP negative. The log-rank test was
      used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox
      regression was used to adjust for additional covariates. RESULTS: Median survival
      was 55 versus 22 months (P < 0.001) in female patients with and without tumor
      PTHrP, respectively. Male survival was 38 months independent of PTHrP status.
      Stage, histology, age, and smoking history were also associated with increased
      longevity. PTHrP remained a significant predictor of survival for female patients
      after controlling for stage, histology, and age. CONCLUSIONS: In this study,
      PTHrP expression was associated with a survival advantage in female patients.
      Additional investigations must be done to ascertain whether the result is
      reproducible and independent of potential confounding covariates. Sex-dependent
      effects of PTHrP in lung cancer would open new avenues of research into the role
      of sex in cancer progression.

PMID- 16428494
TI  - Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer
      patients: a report from the Children's Oncology Group.
AB  - PURPOSE: Vinorelbine (Navelbine) is an orally absorbable Vinca with broad
      antitumor activity. It differs from other Vinca in that it is structurally
      modified on the catharanthine nucleus and has differential actions on tubulin
      that render it less neurotoxic than other compounds in this class. We conducted a
      phase I study of vinorelbine given the activity of Vinca alkaloids in many
      pediatric tumors. EXPERIMENTAL DESIGN: We evaluated the safety and
      pharmacokinetics of oral and i.v. vinorelbine administered weekly x 6 in children
      (age, 2-17 years) with different tumors. Patients with disease involvement in the
      bone marrow were eligible but were stratified and dose-escalated separately. Oral
      vinorelbine (week 1) was administered as liquid-filled gelatin capsules at thrice
      the i.v. dose. Intravenous vinorelbine doses of 24 to 37.5 mg/m(2) were
      administered on weeks 2 to 6. RESULTS: The dose-limiting toxicity in patients
      without marrow involvement was reversible neutropenia. Common nonhematologic
      toxicities included < or = grade 2 nausea/vomiting and increased hepatic
      transaminases. A higher mean i.v. Cl(TB) was observed (1.75 +/- 1.0 L/h/kg)
      compared with adult reports, with a mean t(1/2B) of 16.5 +/- 9.7 hours. Mean oral
      bioavailability was 28.5 +/- 22.5%. The apparent oral clearance (12.1 +/- 13.0
      L/h/kg) and volume of distribution (69.4 +/- 30.6 L/kg) were substantially higher
      than in adults given similar oral doses. CONCLUSIONS: The maximum tolerated dose
      in children without bone marrow involvement was 30 mg/m(2), similar to that
      reported in adults, with myelosuppression being the dose-limiting toxicity.
      Higher plasma clearance resulted in lower area under the plasma concentration
      time curves at a given dose compared with that reported in adults.

PMID- 16428495
TI  - Phase I study of the taxane BMS-188797 in combination with carboplatin
      administered every 3 weeks in patients with solid malignancies.
AB  - RATIONALE: BMS-188797 is one of several novel taxanes in ongoing clinical
      development. It has superior activity in experimental tumor models when compared
      with paclitaxel. BMS-188797 has a single C-4 modification, a 4-desacetyl-4
      methylcarbonate, compared with paclitaxel. METHODS: We did a phase I study, in
      which a fixed dose of carboplatin was combined with a dose escalation schedule of
      BMS-188797, both administered once every 3 weeks, in patients with advanced solid
      malignancies. RESULTS: Thirty patients were treated, 11 at the proposed
      recommended phase II dose. The dose-limiting toxicity was myelosuppression. There
      was a linear relationship between administered dose of BMS-188797 and the
      measured area under the curve (AUC). There was significant interpatient
      variability of BMS-188797 AUC at the maximum tolerated dose. Two radiographic
      partial responses were observed: one patient with duodenal adenocarcinoma and one
      patient with esophageal adenocarcinoma (time on study, 19 and 30 weeks,
      respectively). CONCLUSION: The recommended phase II dose for BMS-188797 and
      carboplatin administered on a once-every-3 week schedule is carboplatin AUC = 5
      mg min/mL and BMS-188797 at a dose of 135 mg/m(2).

PMID- 16428496
TI  - MOPPEBVCAD chemotherapy with limited and conditioned radiotherapy in advanced
      Hodgkin's lymphoma: 10-year results, late toxicity, and second tumors.
AB  - PURPOSE: MOPPEBVCAD (mechlorethamine, vincristine, procarbazine, prednisone,
      epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine)
      chemotherapy with limited radiotherapy was devised in 1987 to reduce late
      toxicity and second tumor incidence while trying to improve effectiveness through
      increases of dose intensity and dose density. Late results, toxicity, and second
      tumor incidence were reviewed in all the patients treated. EXPERIMENTAL DESIGN:
      The drugs of three previous alternating regimens [CAD (lomustine, melphalan, and
      vindesine), MOPP (mechlorethamine, vincristine, procarbazine, and prednisone),
      and ABV (doxorubicin, bleomycin, and vinblastine)] were intensified and
      hybridized, the cumulative dose of mechlorethamine was lowered, and irradiation
      was delivered to no more than two sites either bulky or partially responding to
      chemotherapy. RESULTS: A total of 307 previously untreated advanced-stage
      patients underwent MOPPEBVCAD chemotherapy. Radiotherapy was delivered to 118 of
      307 patients (38%). Remission was complete in 290 patients (94%). With a median
      follow-up of 114 months, 10-year overall, disease-free, and failure-free survival
      rates were 79%, 84%, and 71%, respectively. Forty-two patients relapsed and 60
      died. The causes of death were Hodgkin's lymphoma in 36 patients, second
      neoplasms in 12, cardiorespiratory diseases in 4, pulmonary diseases in 2, and
      unknown in 6. Sixteen second tumors (of which nine were myelodysplasia and/or
      acute leukemia) were diagnosed in all. Outside this series of 307 patients,
      MOPPEBVCAD obtained complete responses in 12 of 15 relapsed and 9 of 9 refractory
      patients who had previously been treated with other regimens. CONCLUSIONS:
      Clinical response and long-term results are very satisfactory, whereas the second
      tumor incidence was lower than would have been expected with MOPP analogues.
      Given its response/late toxicity balance, MOPPEBVCAD does not undermine the
      leading role of ABVD as first-line regimen but can be indicated as a very
      effective second-line conventional therapy.

PMID- 16428497
TI  - Two drug interaction studies evaluating the pharmacokinetics and toxicity of
      pemetrexed when coadministered with aspirin or Ibuprofen in patients with
      advanced cancer.
AB  - PURPOSE: Pemetrexed is an antimetabolite that is structurally similar to
      methotrexate. Because nonsteroidal anti-inflammatory drugs (NSAID) impair
      methotrexate clearance and increase its toxicity, we evaluated the
      pharmacokinetics and toxicity of pemetrexed when coadministered with aspirin or
      ibuprofen in advanced cancer patients. EXPERIMENTAL DESIGN: In two independent,
      randomized, crossover drug interaction studies, cancer patients with a creatinine
      clearance (CrCl) > or =60 mL/min received an NSAID (aspirin or ibuprofen) with
      either the first or the second dose of pemetrexed (cycle 1 or 2). Pemetrexed (500
      mg/m(2)) was infused i.v. on day 1 of a 21-day cycle, and all patients were
      supplemented with oral folic acid and i.m. vitamin B(12). Aspirin (325 mg) or
      ibuprofen (400 mg; 2 x 200 mg) was given orally every 6 hours, starting 2 days
      before pemetrexed administration, with the ninth and final dose taken 1 hour
      before infusion. Pemetrexed pharmacokinetics with and without concomitant NSAID
      treatment were compared for cycles 1 and 2. RESULTS: Data from 27 patients in
      each study were evaluable for the analysis of pemetrexed pharmacokinetics.
      Coadministration of aspirin did not alter pemetrexed pharmacokinetics; however,
      ibuprofen coadministration was associated with a 16% reduction in clearance, a
      15% increase in maximum plasma concentration, and a 20% increase in area under
      the plasma concentration versus time curve but no significant change in V(ss)
      compared with pemetrexed alone. No febrile neutropenia occurred in any patient,
      and no increase in pemetrexed-related toxicity was associated with NSAID
      administration. CONCLUSIONS: Pemetrexed (500 mg/m(2)) with vitamin
      supplementation is well tolerated and requires no dosage adjustment when
      coadministered with aspirin (in patients with CrCl > or =60 mL/min) or ibuprofen
      (in patients with CrCl > or =80 mL/min).

PMID- 16428498
TI  - Long-term clinical outcome of phase IIb clinical trial of percutaneous injection
      with holmium-166/chitosan complex (Milican) for the treatment of small
      hepatocellular carcinoma.
AB  - PURPOSE: The purpose of this study was to evaluate the long-term tumor response
      after phase IIb clinical study and the safety of percutaneous holmium-166
      ((166)Ho)/chitosan complex injection (PHI) therapy for small hepatocellular
      carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived
      from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong
      Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the
      radioactive material within the tumor. EXPERIMENTAL DESIGN: Forty patients with
      single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this
      study. The patients either had refused surgery or were poor surgical candidates
      and were treated with only single session of PHI. RESULTS: Two months after PHI,
      complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with
      hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with
      hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long
      term follow-up period, of which 24 recurred at another intrahepatic site. The 1
      year and 2-year cumulative local recurrence rates were 18.5% and 34.9%,
      respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and
      65.3%, respectively. Transient bone marrow depression was serious adverse event
      requiring hospitalization in two patients. CONCLUSIONS: PHI was found to be a
      safe and novel local ablative procedure for the treatment of small hepatocellular
      carcinoma and could be used as a bridge to transplantation. A phase III
      randomized active control trial is clearly warranted among a larger study
      population.

PMID- 16428499
TI  - The uracil breath test in the assessment of dihydropyrimidine dehydrogenase
      activity: pharmacokinetic relationship between expired 13CO2 and plasma [2
      13C]dihydrouracil.
AB  - PURPOSE: Dihydropyrimidine dehydrogenase (DPD) deficiency is critical in the
      predisposition to 5-fluorouracil dose-related toxicity. We recently characterized
      the phenotypic [2-(13)C]uracil breath test (UraBT) with 96% specificity and 100%
      sensitivity for identification of DPD deficiency. In the present study, we
      characterize the relationships among UraBT-associated breath (13)CO(2) metabolite
      formation, plasma [2-(13)C]dihydrouracil formation, [2-(13)C]uracil clearance,
      and DPD activity. EXPERIMENTAL DESIGN: An aqueous solution of [2-(13)C]uracil (6
      mg/kg) was orally administered to 23 healthy volunteers and 8 cancer patients.
      Subsequently, breath (13)CO(2) concentrations and plasma [2-(13)C]dihydrouracil
      and [2-(13)C]uracil concentrations were determined over 180 minutes using IR
      spectroscopy and liquid chromatography-tandem mass spectrometry, respectively.
      Pharmacokinetic variables were determined using noncompartmental methods.
      Peripheral blood mononuclear cell (PBMC) DPD activity was measured using the DPD
      radioassay. RESULTS: The UraBT identified 19 subjects with normal activity, 11
      subjects with partial DPD deficiency, and 1 subject with profound DPD deficiency
      with PBMC DPD activity within the corresponding previously established ranges.
      UraBT breath (13)CO(2) DOB(50) significantly correlated with PBMC DPD activity
      (r(p) = 0.78), plasma [2-(13)C]uracil area under the curve (r(p) = -0.73), [2
      (13)C]dihydrouracil appearance rate (r(p) = 0.76), and proportion of [2
      (13)C]uracil metabolized to [2-(13)C]dihydrouracil (r(p) = 0.77; all Ps < 0.05).
      CONCLUSIONS: UraBT breath (13)CO(2) pharmacokinetics parallel plasma [2
      (13)C]uracil and [2-(13)C]dihydrouracil pharmacokinetics and are an accurate
      measure of interindividual variation in DPD activity. These pharmacokinetic data
      further support the future use of the UraBT as a screening test to identify DPD
      deficiency before 5-fluorouracil-based therapy.

PMID- 16428500
TI  - Delta-24 increases the expression and activity of topoisomerase I and enhances
      the antiglioma effect of irinotecan.
AB  - PURPOSE: In this study, we sought to determine whether Delta-24 could sensitize
      glioma cells to the topoisomerase I inhibitor irinotecan (CPT-11) and to identify
      the mechanisms underlying this enhanced anticancer effect. EXPERIMENTAL DESIGN:
      We used human glioblastoma cell lines for the in vitro studies. The expression of
      topoisomerase I was determined in Western blot analyses, and topoisomerase I
      activity was determined by measuring the relaxation of a supercoiled DNA. The
      cell cycle distribution of cells was determined by flow cytometry analysis of the
      cellular DNA content. Cell viability was quantified by a 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay. Tissue culture infection dose assays
      were used to quantitate adenovirus replication. For the in vivo studies, athymic
      mice received intracranial/intratumoral injections of Delta-24 in combination
      with CPT-11, after which animal survival was monitored. RESULTS: Delta-24
      infection caused human glioma cells to accumulate in the S phase and induced the
      expression and activity of topoisomerase I as shown by Western blot and in vitro
      enzymatic activity assays. Further, we showed that the sequential administration
      of Delta-24 and CPT-11 to human glioma cell cultures potentiated the CPT-11
      mediated anticancer effect in vitro without modifying the replicative phenotype
      of the oncolytic adenovirus. In vivo experiments showed that the single
      intratumoral administration of Delta-24 to intracranially implanted human glioma
      xenografts followed by the systemic administration of CPT-11 resulted in
      significantly prolonged animal survival. CONCLUSIONS: The combination of Delta-24
      treatment with CPT-11 showed an enhanced anticancer effect, which suggests that
      the interaction between adenoviral and human proteins can be exploited in
      rational anticancer therapies comprising replication-competent adenoviruses and
      conventional chemotherapeutic agents.

PMID- 16428501
TI  - DNA polymerase zeta accounts for the reduced cytotoxicity and enhanced
      mutagenicity of cisplatin in human colon carcinoma cells that have lost DNA
      mismatch repair.
AB  - The mutagenicity of cis-diamminedichloroplatinum(II) (DDP; cisplatin) and the
      rate at which resistance develops with repeated exposure to DDP are dependent on
      mutagenic translesional replication across DDP DNA adducts, mediated in part by
      DNA polymerase zeta, and on the integrity of the DNA mismatch repair (MMR)
      system. The aim of this study was to determine whether disabling Pol zeta by
      suppressing expression of its hREV3 subunit in human cancer cells can reduce the
      mutagenicity of DDP and whether loss of MMR facilitates mutagenic Pol zeta
      dependent translesional bypass. The HCT116+ch3 (MMR(+)/REV3(+)) and HCT116 (MMR(
      )/REV3(+)) human colon carcinoma cell lines were engineered to suppress hREV3
      mRNA by stable expression of a short hairpin interfering RNA targeted to hREV3.
      The effect of knocking down REV3 expression was to completely offset the DDP
      resistance mediated by loss of MMR. Knockdown of REV3 also reduced the
      mutagenicity of DDP and eliminated the enhanced mutagenicity of DDP observed in
      the MMR(-)/REV3(+) cells. Similar results were obtained when the ability of the
      cells to express luciferase from a platinated plasmid was measured. We conclude
      that Pol zeta plays a central role in the mutagenic bypass of DDP adducts and
      that the DDP resistance, enhanced mutagenicity, and the increased capacity of
      MMR(-)/REV3(+) cells to express a gene burdened by DDP adducts are all dependent
      on the Pol zeta pathway.

PMID- 16428502
TI  - Human T cells armed with Her2/neu bispecific antibodies divide, are cytotoxic,
      and secrete cytokines with repeated stimulation.
AB  - PURPOSE: Cancer immunotherapy has been limited by anergy of patient T cells,
      inadequate numbers of precursor tumor-specific CTL, and difficulty in producing
      therapeutic doses of CTL. To overcome these limitations, bispecific antibodies
      have been used to create artificial antibody receptors that direct polyclonal
      activated T cells (ATC) to target tumor antigens. Studies reported herein were
      designed to characterize bispecific antibody-armed ATC functions during multiple
      rounds of targeted cell stimulation. EXPERIMENTAL DESIGN: ATCs were generated
      from human peripheral blood mononuclear cells (PBMC) by culture with anti-CD3 and
      interleukin 2 for 14 days and armed with anti-CD3 x anti-Her2 bispecific antibody
      (Her2Bi). In vitro, Her2Bi-armed ATC were examined for a range of functions after
      repeated stimulation with the Her2/neu-expressing breast cancer cell line SK-BR
      3. PBMC isolated from cancer patients treated with Her2Bi-armed ATC were tested
      ex vivo for cytotoxicity against SK-BR-3. RESULTS: In vitro, armed ATC divided,
      maintained surface Her2Bi, and expressed a range of activities for extended
      periods of time. Perforin-mediated cytotoxic activity by armed ATC continued for
      at least 336 hours, and cytokines and chemokines (i.e., IFN-gamma and regulated
      on activation, normal T-cell expressed and secreted protein [RANTES]) were
      secreted during successive rounds of stimulation. Furthermore, PBMC isolated from
      patients over their courses of immunotherapy exhibited significant cytolytic
      activity against SK-BR-3 as a function of Her2Bi-armed ATC infusions.
      CONCLUSIONS: These studies show that armed ATC are specific, durable, and highly
      functional T-cell populations in vitro. These previously unappreciated broad and
      long-term functions of armed ATC are encouraging for their therapeutic use in
      treating cancer.

PMID- 16428503
TI  - Novel toll-like receptor 9 agonist induces epidermal growth factor receptor
      (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitors.
AB  - PURPOSE: Immunostimulating Toll-like receptor 9 (TLR9) agonists cause antitumor
      activity interfering also with cancer proliferation and angiogenesis by
      mechanisms still incompletely understood. We hypothesized that modified TLR9
      agonists could impair epidermal growth factor receptor (EGFR) signaling and, by
      this means, greatly enhance EGFR inhibitors effect, acting on both the receptor
      targeting and the immunologic arm. EXPERIMENTAL DESIGN: We used a novel second
      generation, modified, immunomodulatory TLR9 agonist (IMO), alone and in
      combination with the anti-EGFR monoclonal antibody cetuximab or tyrosine kinase
      inhibitor gefitinib, on the growth of GEO and cetuximab-resistant derivatives GEO
      CR colon cancer xenografts. We have also evaluated the expression of several
      proteins critical for cell proliferation, apoptosis, and angiogenesis, including
      EGFR, mitogen-activated protein kinase, Akt, bcl-2, cyclooxygenase-2, vascular
      endothelial growth factor, and nuclear factor-kappaB. RESULTS: IMO inhibited GEO
      growth and signaling by EGFR and the other proteins critical for cell
      proliferation and angiogenesis. IMO plus the anti-EGFR antibody cetuximab
      synergistically inhibited tumor growth, signaling proteins, and microvessel
      formation. EGFR signaling inhibition by IMO is relevant because IMO cooperated
      also with EGFR tyrosine kinase inhibitor gefitinib in GEO tumors, while it was
      inactive against GEO-CR xenografts. On the other hand, IMO boosted the non-EGFR
      dependent cetuximab activity, causing a cooperative antitumor effect in GEO-CR
      cells. Finally, combination of IMO, cetuximab and chemotherapeutic irinotecan
      eradicated the tumors in 90% of mice. CONCLUSION: IMO interferes with EGFR
      related signaling and angiogenesis and has a synergistic antitumor effect with
      EGFR inhibitors, especially with cetuximab, boosting both the EGFR dependent and
      independent activity of this agent. Moreover, this therapeutic strategy could be
      translated in patients affected by colorectal cancer.

PMID- 16428504
TI  - Inhibition of heat shock protein 90 function by 17-allylamino-17-demethoxy
      geldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinase,
      dephosphorylates extracellular signal-regulated kinase, and induces cell cycle
      arrest and cell death.
AB  - PURPOSE: Heat shock protein 90 (HSP90) is a chaperone for several client proteins
      involved in transcriptional regulation, signal transduction, and cell cycle
      control. HSP90 is abundantly expressed by a variety of tumor types and has been
      recently targeted for cancer therapy. The objective of this study was to
      determine the role of HSP90 in promoting growth and survival of Hodgkin's
      lymphoma and to determine the molecular consequences of inhibiting HSP90 function
      by the small-molecule 17-allylamino-17-demethoxy-geldanamycin (17-AAG) in
      Hodgkin's lymphoma. EXPERIMENTAL DESIGN: HSP90 expression in Hodgkin's lymphoma
      cell lines was determined by Western blot and in primary lymph node sections from
      patients with Hodgkin's lymphoma by immunohistochemistry. Cell viability was
      determined by the 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) assay. Apoptosis and cell cycle fractions were
      determined by flow cytometry. Expression of intracellular proteins was determined
      by Western blot. RESULTS: HSP90 is overexpressed in primary and cultured
      Hodgkin's lymphoma cells. Inhibition of HSP90 function by 17-AAG showed a time-
      and dose-dependent growth inhibition of Hodgkin's lymphoma cell lines. 17-AAG
      induced cell cycle arrest and apoptosis, which were associated with a decrease in
      cyclin-dependent kinase (CDK) 4, CDK 6, and polo-like kinase 1 (PLK1), and
      induced apoptosis by caspase-dependent and caspase-independent mechanisms.
      Furthermore, 17-AAG depleted cellular contents of Akt, decreased extracellular
      signal-regulated kinase (ERK) phosphorylation, and reduced cellular FLICE-like
      inhibitory protein levels (FLIP), and thus enhanced the cytotoxic effect of
      doxorubicin and agonistic anti-tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) death receptor antibodies. CONCLUSION: Inhibition of HSP90
      function induces cell death and enhances the activity of chemotherapy and anti
      tumor necrosis factor-related apoptosis-inducing ligand death receptor
      antibodies, suggesting that targeting HSP90 function might be of therapeutic
      value in Hodgkin's lymphoma.

PMID- 16428505
TI  - Tipifarnib and bortezomib are synergistic and overcome cell adhesion-mediated
      drug resistance in multiple myeloma and acute myeloid leukemia.
AB  - It has been established in preclinical models of multiple myeloma and acute
      myeloid leukemia (AML) that the bone marrow microenvironment provides protection
      from chemotherapy- and death receptor-mediated apoptosis. This form of
      resistance, termed de novo drug resistance, occurs independent of chronic
      exposure to cancer-related therapies and likely promotes the development of
      multidrug resistance. Consequently, it is of major interest to identify compounds
      or drug combinations that can overcome environment-mediated resistance. In this
      study, we investigated the activity of tipifarnib (Zarnestra, formerly R115777)
      combined with bortezomib (Velcade, formerly PS-341) in microenvironment models of
      multiple myeloma and AML. The combination proved to be synergistic in multiple
      myeloma and AML cell lines treated in suspension culture. Even in tumor cells
      relatively resistant to tipifarnib, combined activity was maintained. Tipifarnib
      and bortezomib were also effective when multiple myeloma and AML cells were
      adhered to fibronectin, providing evidence that the combination overcomes cell
      adhesion-mediated drug resistance (CAM-DR). Of importance, activation of the
      endoplasmic reticulum stress response was enhanced and correlated with apoptosis
      and reversal of CAM-DR. Multiple myeloma and AML cells cocultured with bone
      marrow stromal cells also remained sensitive, although stromal-adhered tumor
      cells were partially protected (relative to cells in suspension or fibronectin
      adhered). Evaluation of the combination using a transwell apparatus revealed that
      stromal cells produce a protective soluble factor. Investigations are under way
      to identify the cytokines and/or growth factors involved. In summary, our study
      provides the preclinical rationale for trials testing the tipifarnib and
      bortezomib combination in patients with multiple myeloma and AML.

PMID- 16428507
TI  - Transcriptional regulation of the human reduced folate carrier in childhood acute
      lymphoblastic leukemia cells.
AB  - PURPOSE: The transcriptional regulation of the human reduced folate carrier
      (hRFC), involved in cellular uptake of methotrexate and reduced folates, was
      studied in childhood acute lymphoblastic leukemia (ALL). The hRFC gene is
      regulated by six noncoding exons (A1/A2 and A to E) and multiple promoters. In
      ALL, hRFC-A1/A2 and hRFC-B are the major transcript forms. EXPERIMENTAL DESIGN:
      RNAs from 18 ALL lymphoblast specimens and 10 nonobese diabetic/severe combined
      immunodeficient ALL xenografts were assayed by real-time reverse transcription
      PCR for hRFC-A1/A2 and hRFC-B transcripts and for transcripts encoding USF1,
      GATA1, Sp1, and Ikaros transcription factors. For the xenografts, gel shift and
      chromatin immunoprecipitation assays assessed transcription factor binding to the
      hRFC-A1/A2 and hRFC-B promoters. CpG methylation density within a 334-bp region,
      including the core hRFC-B promoter, was established by bisulfite sequencing. hRFC
      A1/A2 and hRFC-B promoter polymorphisms were assayed by DNA sequencing. RESULTS:
      For the 28 ALLs, hRFC-A1/A2 and hRFC-B transcripts spanned a 546-fold range. By
      chromatin immunoprecipitation and gel shift assays, binding was confirmed for
      USF1 and GATA1 for hRFC-A1/A2, and for Sp1, USF1, and Ikaros for hRFC-B. hRFC
      transcript levels correlated with those for GATA1 and USF1 for hRFC-A1/A2 and
      with Sp1 and USF1 transcripts for hRFC-B. CpG methylation in ALL did not
      correlate with hRFC-B transcripts. In 40 ALL and 17 non-ALL specimens, 2
      cosegregating high-frequency polymorphisms (T-1309/C-1217 and C-1309/T-1217;
      allelic frequencies of 36% and 64%, respectively) were detected in the A1/A2
      promoter; none were detected in promoter B. The hRFC-A1/A2 polymorphisms only
      slightly affected promoter activity. CONCLUSIONS: Our results show a complex
      regulation of hRFC in ALL involving the hRFC-A1/A2 and hRFC-B promoters and
      noncoding exons. Although Sp1, USF1, and GATA1 levels are critical determinants
      of hRFC transcription in ALL, neither DNA methylation nor promoter polymorphisms
      contribute to differences in hRFC expression.

PMID- 16428508
TI  - Synergistic antitumor activity of epidermal growth factor receptor tyrosine
      kinase inhibitor gefitinib and IFN-alpha in head and neck cancer cells in vitro
      and in vivo.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) overexpression has been
      implicated in the development of head and neck squamous cell carcinomas (HNSCC)
      and represents a potential therapeutic target for this disease. We have reported
      previously that growth inhibitory concentrations of IFN-alpha enhance the
      expression and activity of EGFR and that this effect could represent an escape
      mechanism to the growth inhibition and apoptotic cell death induced by IFN-alpha.
      In this study, we investigate whether the combination of IFN-alpha and gefitinib
      (Iressa, AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom), a selective
      EGFR tyrosine kinase inhibitor, might have a cooperative antitumor effect on
      HNSCC-derived cell lines. EXPERIMENTAL DESIGN: The interaction of IFN-alpha and
      gefitinib was evaluated in vitro on HNSCC-derived cell lines by median drug
      effect analysis calculating a combination index with CalcuSyn software and in
      vivo by using HNSCC xenografts in nude mice. The mechanism of gefitinib and IFN
      alpha interactions was also studied by analysis of cell cycle kinetics, apoptosis
      assays, and Western blotting of EGFR signal transduction components. RESULTS:
      Simultaneous exposure to gefitinib and IFN-alpha produced synergistic
      antiproliferative and proapoptotic effects compared with single drug treatment.
      Furthermore, daily treatment of gefitinib (50 mg/kg p.o.) in combination with an
      IFN-alpha regimen (50,000 units s.c. three times weekly) induced tumor growth
      delay and increased survival rate on established HNSCC xenografts in nude mice.
      Moreover, the concomitant treatment with gefitinib suppressed the stimulation of
      extracellular signal-regulated kinase phosphorylation/activity induced by IFN
      alpha both in vitro and in vivo. CONCLUSION: The observed cooperative antitumor
      effects could be, at least in part, explained by the inhibition exerted by
      gefitinib of an IFN-alpha-induced EGF-dependent survival pathway, which involves
      extracellular signal-regulated kinase activation. These results provide a
      rationale for the clinical evaluation of gefitinib in combination with IFN-alpha
      in HNSCC.

PMID- 16428506
TI  - Cetuximab and irinotecan interact synergistically to inhibit the growth of
      orthotopic anaplastic thyroid carcinoma xenografts in nude mice.
AB  - PURPOSE: Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known
      human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody
      against epidermal growth factor receptor, offers new treatment potentials for
      patient with ATC. Cetuximab has also been reported to have synergistic effects
      when combined with irinotecan, a topoisomerase inhibitor. Therefore, we
      hypothesized that cetuximab and irinotecan would be effective in inhibiting the
      growth and progression of ATC in a murine orthotopic model. EXPERIMENTAL DESIGN:
      The in vitro antiproliferative effects of cetuximab and irinotecan on ATC cell
      line ARO were examined. We also studied the in vivo effects of cetuximab and
      irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in
      nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was
      also compared with that of doxorubicin. RESULTS: Cetuximab alone did not show any
      antiproliferative or proapoptotic effect on this cell line. However, when
      combined with irinotecan, cetuximab potentiated the in vitro antiproliferative
      and proapoptotic effect of irinotecan. Cetuximab, irinotecan, and
      cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition
      of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal
      invasion, and tumor microvessel density were also significantly decreased in
      these treatment groups. Furthermore, the cetuximab/irinotecan combination was
      significantly more effective than doxorubicin in inhibiting the growth of
      orthotopic ATC xenografts. CONCLUSIONS: Combination therapy with
      cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC
      xenografts in nude mice. Given the lack of curative options for patients with
      ATC, combination therapy with cetuximab and irinotecan treatment warrants further
      study.

PMID- 16428509
TI  - Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to
      granulocyte-colony stimulating factor in vitro promotes their elimination by
      imatinib mesylate.
AB  - PURPOSE: Primitive quiescent chronic myeloid leukemia (CML) cells are
      biologically resistant to imatinib mesylate, an inhibitor of the p210(BCR-ABL)
      kinase. The present study was designed to investigate whether either continuous
      or intermittent exposure of these cells to granulocyte-colony stimulating factor
      (G-CSF) in vitro can overcome this limitation to the effectiveness of imatinib
      mesylate therapy. EXPERIMENTAL DESIGN: CD34(+) leukemic cells were isolated from
      six newly diagnosed chronic phase CML patients and cultured for 12 days in serum
      free medium with or without G-CSF and/or imatinib mesylate present either
      continuously or intermittently (three cycles of G-CSF for 0, 1, or 4 days +/-
      imatinib mesylate for 0, 3, or 4 days). Every 4 days, the number of residual
      undivided viable cells and the total number of viable cells present were
      measured. RESULTS: Intermittent but not continuous exposure to G-CSF
      significantly accelerated the disappearance in vitro of initially quiescent
      CD34(+) CML cells. This resulted in 3- and 5-fold fewer of these cells remaining
      after 8 and 12 days, respectively, relative to continuous imatinib mesylate alone
      (P < 0.04). Cultures containing imatinib mesylate and intermittently added G-CSF
      also showed the greatest reduction in the total number of cells present after 12
      days (5-fold more than imatinib mesylate alone). CONCLUSION: Intermittent
      exposure to G-CSF can enhance the effect of imatinib mesylate on CML cells by
      specifically targeting the primitive quiescent leukemic elements. A protocol for
      treating chronic-phase CML patients with imatinib mesylate that incorporates
      intermittent G-CSF exposure may offer a novel strategy for obtaining improved
      responses in vivo.

PMID- 16428511
TI  - Triple combination of oncolytic herpes simplex virus-1 vectors armed with
      interleukin-12, interleukin-18, or soluble B7-1 results in enhanced antitumor
      efficacy.
AB  - Conditionally replicating herpes simplex virus-1 (HSV-1) vectors are promising
      therapeutic agents for cancer. Insertion of therapeutic transgenes into the viral
      genome should confer desired anticancer functions in addition to oncolytic
      activities. Herein, using bacterial artificial chromosome and two recombinase
      mediated recombinations, we simultaneously created four "armed" oncolytic HSV-1,
      designated vHsv-B7.1-Ig, vHsv-interleukin (IL)-12, vHsv-IL-18, and vHsv-null,
      which express murine soluble B7.1 (B7.1-Ig), murine IL-12, murine IL-18, and no
      transgene, respectively. These vHsv vectors possess deletions in the gamma34.5
      genes and contain the green fluorescent protein gene as a histochemical marker
      and the immunostimulatory transgene inserted in the deleted ICP6 locus. The vHsv
      showed similar replicative capabilities in vitro. The in vivo efficacy was tested
      in A/J mice harboring s.c. tumors of syngeneic and poorly immunogenic Neuro2a
      neuroblastoma. The triple combination of vHsv-B7.1-Ig, vHsv-IL-12, and vHsv-IL-18
      exhibited the highest efficacy among all single vHsv or combinations of two
      viruses. Combining 1 x 10(5) plaque-forming units each of the three armed viruses
      showed stronger antitumor activities than any single armed virus at 3 x 10(5)
      plaque-forming units in inoculated tumors as well as in noninoculated remote
      tumors. Studies using athymic mice indicated that this enhancement of antitumor
      efficacy was likely mediated by T-cell immune responses. The combined use of
      multiple oncolytic HSV-1 armed with different immunostimulatory genes may be a
      useful strategy for cancer therapy.

PMID- 16428510
TI  - Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic
      acid derivative LBH589.
AB  - PURPOSE: Angiogenesis is required for tumor progression and represents a rational
      target for therapeutic intervention. Histone deacetylase (HDAC) inhibitors have
      been shown to have activity against various tumor cell types by inhibiting
      proliferation and inducing apoptosis both in vitro and in vivo. HDAC inhibitors
      have also been reported to inhibit angiogenesis. The goal of this study was to
      characterize the antiangiogenic and antitumor activity of a recently developed
      HDAC inhibitor, the hydroxamic derivative LBH589. MATERIALS AND METHODS: To
      evaluate the antiangiogenesis activity of LBH589, we did cell cycle analysis,
      cell proliferation, tube formation, invasion assays in vitro, and Matrigel plug
      assay in vivo. To determine the antitumor activity of LBH589, we established
      human prostate carcinoma cell PC-3 xenografts in vivo. To evaluate the effect of
      LBH589 on endothelial signaling pathways, gene expression, and protein
      acetylation, we did Western blots and reverse transcription-PCR in human
      umbilical vein endothelial cells (HUVEC). Immunohistochemical analysis was done
      to evaluate new blood vessel formation in vivo. RESULTS: LBH589 induced
      acetylation of histone H3 and alpha-tubulin protein in HUVECs. Histone and
      nonhistone protein acetylation correlated with induction of G(2)-M cell cycle
      arrest, inhibition of HUVEC proliferation, and viability. Noncytotoxic
      concentrations of LBH589 inhibited endothelial tube formation, Matrigel invasion,
      AKT, extracellular signal-regulated kinase 1/2 phosphorylation, and chemokine
      receptor CXCR4 expression. In vivo dosing of mice with LBH589 (10 mg/kg/d)
      reduced angiogenesis and PC-3 tumor growth. CONCLUSION: This study provides
      evidence that LBH589 induces a wide range of effects on endothelial cells that
      lead to inhibition of tumor angiogenesis. These results support the role of HDAC
      inhibitors as a therapeutic strategy to target both the tumor and endothelial
      compartment and warrant the clinical development of these agents in combination
      with angiogenesis inhibitors.

PMID- 16428512
TI  - Identification of insulin-like growth factor binding protein-3 as a farnesyl
      transferase inhibitor SCH66336-induced negative regulator of angiogenesis in head
      and neck squamous cell carcinoma.
AB  - The farnesyl transferase inhibitor (FTI) SCH66336 has been shown to have
      antitumor activities in head and neck squamous cell carcinoma (HNSCC) in vitro
      and in vivo. However, its mechanism of action has not been well defined. Here, we
      report that the insulin-like growth factor (IGF) binding protein (IGFBP)-3
      mediates antitumor activities of SCH66336 in HNSCC by inhibiting angiogenesis.
      SCH66336 significantly suppressed HNSCC tumor growth and angiogenesis via
      mechanisms that are independent of H-Ras and RhoB. By inducing IGFBP-3 secretion
      from HNSCC cells, this compound suppresses angiogenic activities of endothelial
      cells, including vessel formation in chorioallantoic membranes of chick,
      endothelial cell sprouting from chick aorta, and capillary tube formation of
      human umbilical vascular endothelial cells (HUVEC). Knockdown of IGFBP-3
      expression in HNSCC cells by RNA interference or depletion of IGFBP-3 in HUVECs
      by neutralizing antibody effectively blocked the effects of IGFBP-3 secreted from
      SCH66336-treated HNSCC cells on HUVECs. These findings suggest that IGFBP-3 could
      be a primary target for antitumor activities of FTIs and that IGFBP-3 is an
      effective therapeutic approach against angiogenesis in HNSCC.

PMID- 16428514
TI  - Lost in (the business of) translation: invest in the youth.

PMID- 16428513
TI  - Guggulsterone inhibits osteoclastogenesis induced by receptor activator of
      nuclear factor-kappaB ligand and by tumor cells by suppressing nuclear factor
      kappaB activation.
AB  - Bone resorption is commonly associated with aging and with certain types of
      cancer, including multiple myeloma and breast cancer. What induces bone
      resorption is not fully understood, but the role of osteoclasts is well
      established. Recently, receptor activator of nuclear factor-kappaB (NF-kappaB)
      ligand (RANKL), a member of the tumor necrosis factor superfamily, was implicated
      as a major mediator of bone resorption, suggesting that agents that can suppress
      RANKL signaling have the potential to inhibit bone resorption or
      osteoclastogenesis. Guggulsterone [4,17(20)-pregnadiene-3,16-dione], isolated
      from the guggul tree Commiphora mukul and used to treat osteoarthritis and bone
      fractures, was recently shown to antagonize the farnesoid X receptor, decrease
      the expression of bile acid-activated genes, and suppress the NF-kappaB
      activation induced by various carcinogens. We investigated whether guggulsterone
      could modulate RANKL signaling and osteoclastogenesis induced by RANKL or tumor
      cells. We found that treatment of monocytes with guggulsterone suppressed RANKL
      activated NF-kappaB activation (as indicated by gel-shift assay) and that this
      suppression correlated with inhibition of IkappaBalpha kinase and phosphorylation
      and degradation of IkappaBalpha, an inhibitor of NF-kappaB. Guggulsterone also
      suppressed the differentiation of monocytes to osteoclasts in a dose-dependent
      and time-dependent manner. Suppression of osteoclastogenesis by the NF-kappaB
      specific inhibitory peptide implies a link between NF-kappaB and
      osteoclastogenesis. Finally, differentiation to osteoclasts induced by
      coincubating human breast tumor cells (MDA-MB-468) or human multiple myeloma
      (U266) cells with monocytes was also completely suppressed by guggulsterone.
      Collectively, our results indicate that guggulsterone suppresses RANKL and tumor
      cell-induced osteoclastogenesis by suppressing the activation of NF-kappaB.

PMID- 16428516
TI  - EGFR expression predicts BRCA1 status in patients with breast cancer.

PMID- 16428518
TI  - PRO: Fluid restriction in cardiac patients for noncardiac surgery is beneficial.

PMID- 16428519
TI  - CON: Fluid restriction for cardiac patients during major noncardiac surgery
      should be replaced by goal-directed intravascular fluid administration.

PMID- 16428520
TI  - The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an
      in vitro model.
AB  - Colloids and crystalloids are usually administered as treatment for hypovolemia
      in severely injured patients. However, dilution of clotting factors and platelets
      together with impaired fibrinogen polymerization are associated with fluid
      therapy and may aggravate hemorrhage, thus worsening final outcome of these
      patients. We investigated, in an in vitro model, whether the addition of
      fibrinogen to diluted blood samples can reverse dilutional coagulopathy. Blood
      from 5 healthy male volunteers was diluted by 60% using lactated Ringer's
      solution, 4% modified gelatin solution, or 6% hydroxyethyl starch 130/0.4, as
      well as the combination of lactated Ringer's solution with either of the 2
      colloid solutions. Thereafter, aliquots of diluted blood samples were incubated
      with 3 different concentrations of fibrinogen (0.75, 1.5, and 3.0 mg/mL).
      Measurements were performed by modified thrombelastography (ROTEM; Pentapharm,
      Munich, Germany). After 60% dilution, clotting times increased, whereas clot
      firmness and fibrin polymerization decreased significantly. After administration
      of fibrinogen, clotting times decreased and clot firmness, as well as fibrin
      polymerization, increased in all diluted blood samples. The effect of in vitro
      fibrinogen substitution on ROTEM variables was dependent on the fibrinogen dosage
      and the type of solution used to dilute the blood samples.

PMID- 16428521
TI  - Normothermic beating heart surgery with assistance of miniaturized bypass
      systems: the effects on intraoperative hemodynamics and inflammatory response.
AB  - The use of miniaturized cardiopulmonary bypass (CPB) circuits and avoidance of
      cardioplegic arrest are attempts to reduce the inflammatory response to cardiac
      surgery. We studied the effects of beating heart surgery (BHS) with assistance of
      simplified bypass systems (SBS) on global hemodynamics, myocardial function and
      the inflammatory response to CPB. We hypothesized that the use of SBS was
      associated with less hemodynamic instability after CPB resulting from attenuation
      of the inflammatory response when compared with surgery performed with a
      conventional CPB (cCPB) circuit. Forty-five patients undergoing coronary artery
      bypass grafting were prospectively studied. Fifteen patients were randomized to
      the use of a cCPB circuit, cold crystalloid cardioplegia, and moderate
      hypothermia. Two groups of 15 patients underwent BHS during normothermia with
      assistance of two different SBS consisting of only blood pump and oxygenator.
      Hemodynamic variables were assessed with transpulmonary thermodilution and
      transesophageal echocardiography. Plasma levels of proinflammatory and
      antiinflammatory mediators were measured perioperatively. After CPB, variables of
      global hemodynamics and systolic ventricular function did not differ among
      groups. Left ventricular diastolic function was impaired after CPB equally in all
      groups (P < 0.01 versus pre-CPB). At the end of surgery, there was more need for
      vasopressor (norepinephrine) support in both SBS groups than in the cCPB group (P
      < 0.01). After CPB, the release of interleukin (IL)-6 did not differ
      significantly among groups, whereas plasma levels of IL-10 were higher in the
      cCPB group (P < 0.01 versus SBS). The extent of myocardial necrosis (Troponin T)
      was comparable in all groups. We conclude that in our study, miniaturizing bypass
      systems and avoidance of cardioplegic arrest were not effective in improving
      hemodynamic performance and in attenuating the proinflammatory immune response
      after CPB.

PMID- 16428522
TI  - Inadvertent placement of a flow-directed pulmonary artery catheter in the
      coronary sinus, detected by transesophageal echocardiography.
AB  - We report a case in which flow-directed placement of the pulmonary artery
      catheter led to its inadvertent placement in the coronary sinus, in the absence
      of congenital anomalies. Incorrect placement was diagnosed by use of the
      transesophageal echocardiography. If unrecognized, the catheter might have
      provided misleading information and led to mismanagement of the patient.

PMID- 16428523
TI  - Intraoperative severity assessment of coronary artery stenosis in patients at
      risk: the role of transesophageal echocardiography.
AB  - A 71-yr-old male was scheduled for infrarenal abdominal aortic aneurysm repair.
      Although he had only minor clinical predictors for increased perioperative
      cardiovascular risk with >4 estimated metabolic equivalents for activities,
      intraoperative transesophageal echocardiography revealed an abnormal maximal-to
      prestenotic blood flow velocity ratio in the left main coronary artery.
      Postoperatively, a severe distal left main coronary artery stenosis was confirmed
      with coronary angiography. Understanding the flow velocity patterns in the
      coronary arteries helps the anesthesiologist to detect coronary lesions with
      transesophageal echocardiography.

PMID- 16428524
TI  - Sinus of valsalva aneurysm and ventricular tachycardia during pulmonary artery
      catheterization.
AB  - Pulmonary artery catheterization is associated with numerous complications,
      including serious arrhythmias. We report a case where ventricular tachycardia
      occurred repeatedly during attempted pulmonary artery catheterization, precluding
      successful catheterization. Transesophageal echocardiography was used to image
      the tricuspid valve and right ventricle and revealed a Sinus of Valsalva aneurysm
      protruding significantly into the right ventricle and obstructing advancement of
      the pulmonary artery catheter. Our case reveals another identifiable cause of
      serious arrhythmia during pulmonary artery catheterization and highlights how
      transesophageal echocardiography can be useful in unanticipated ways during
      cardiac anesthesia and surgery.

PMID- 16428525
TI  - Malignant hyperthermia following systemic rewarming after hypothermic
      cardiopulmonary bypass.
AB  - Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscle
      that can be fatal if not recognized and treated aggressively. We describe a
      patient with a suspected family history of MH who developed hyperpyrexia,
      acidosis, and hypermetabolism after cardiac surgery despite a nontriggering
      anesthetic. No drugs were identified as being causative and we theorize that
      systemic rewarming was the inciting cause of MH in this MH-susceptible individual
      via a mechanism similar to heat stroke.

PMID- 16428526
TI  - Bilateral vocal cord palsy during carotid endarterectomy under cervical plexus
      block.
AB  - We describe a case of vocal cord palsy leading to respiratory obstruction during
      carotid endarterectomy under cervical plexus block in a patient who had
      preexisting contralateral vocal cord paralysis subsequent to a previous
      thyroidectomy. The patient required immediate tracheal intubation and subsequent
      tracheostomy to maintain the airway postoperatively. Care must be given to avoid
      contralateral vocal cord paralysis in the presence of a preexisting vocal cord
      palsy.

PMID- 16428527
TI  - Intraoperative renal cell carcinoma tumor embolization to the right atrium:
      incidental diagnosis by transesophageal echocardiography.

PMID- 16428528
TI  - To BIS or not to BIS? That is the question.

PMID- 16428529
TI  - Validation of the bispectral index monitor for measuring the depth of sedation in
      children.
AB  - The Bispectral Index (BIS) is an empirically calibrated number derived from adult
      electroencephalograph data that correlates with the depth of sedation in adults.
      We tested the hypothesis that the BIS score is a valid measure of the depth of
      pediatric sedation in a study designed to avoid limitations of a previously
      published report. BIS values from 96 healthy ASA physical status I-II children
      aged 1-12 yr undergoing sedation were continually recorded and electronically
      transferred to a computer. Two independent observers blinded as to BIS score
      evaluated sedation using the Observer's Assessment of Alertness/Sedation (OAA/S)
      and the University of Michigan Sedation Scale (UMSS) at 3-5 min intervals. There
      was a significant correlation between BIS and UMSS and between BIS and OAA/S by
      both the Spearman's rank correlation test and by prediction probability (P <
      0.001). In children <6 yr, there was a significant correlation between BIS and
      the clinical sedation scores for subgroups undergoing invasive and noninvasive
      procedures (P < 0.001). There was also good agreement between the 2 independent
      observers who assessed clinical sedation scores (kappa = 0.51, P < 0.001). We
      conclude that the BIS monitor is a quantitative, nondisruptive and easy to use
      depth of sedation monitor in children.

PMID- 16428530
TI  - A comparison of observational and objective measures to differentiate depth of
      sedation in children from birth to 18 years of age.
AB  - Several observational and objective methods are available to assess sedation
      depth; however, data regarding their accuracy in differentiating deep sedation
      are limited. In this study we compared 3 sedation tools in children from birth to
      18 yr of age and determined their relative value in detecting deep levels of
      sedation. Bispectral index monitoring (BIS), Modified Maintenance of Wakefulness
      Tests (MMWT), and the University of Michigan Sedation Scale (UMSS) were used to
      assess sedation. Three-hundred-twenty-seven observations were recorded in 39
      children. The overall validity of each measure was supported by appropriate
      changes after sedation administration through the observation period. There were
      moderate to high correlations between UMSS and BIS (rho = -0.73) and UMSS and
      MMWT (rho = -0.59; P < 0.01). The correlation between BIS and MMWT was
      significant but low (r = 0.36; P < 0.01). Measures of exact agreement supported
      the reliability of the UMSS and MMWT across the sedation continuum. There were
      significant decreases in BIS across UMSS scores except from scores 2-3. ROC
      curves suggested that BIS < or = 80 and MMWT < or = 14 min were most sensitive in
      delineating deep sedation. Our findings demonstrate the overall validity of these
      observational and objective measures of sedation depth in children <18 yr of age
      but show ongoing limitations distinguishing moderate from deep sedation.

PMID- 16428531
TI  - Caudal regional anesthesia, ropivacaine concentration, postoperative analgesia,
      and infants.
AB  - In this randomized, double-blind trial we evaluated the quality and duration of
      analgesia and motor effects after caudal block using 1 mL/kg of ropivacaine 0.1%
      (Group 1), 0.15% (Group 2), 0.175% (Group 3) compared to 0.2% (Group 4) in
      infants 1-12 mo old. Postoperatively, the number of infants who received pain
      medication differed among the groups (P < 0.0005). There were more infants in
      Groups 1 and 2 compared with Group 4 and there was no difference between Groups 3
      and 4. In the postanesthesia care unit, infants in Groups 1 and 2 received more
      pain medication than did those in Group 4 (P = 0.0098). In the day surgery unit,
      there was a significant difference among the groups (P = 0.0326); infants in
      Groups 3 and 4 required no pain medication. The analgesia duration differed among
      the groups (P = 0.034). Infants in Groups 1 and 2 had a shorter duration, and
      there was no difference between Groups 3 and 4. Infants in Group 4 took longer to
      regain their motor power compared with those in Group 3 (P = 0.0347). We conclude
      that in infants, ropivacaine 0.175% provided postoperative analgesia and duration
      similar to that of ropivacaine 0.2%, whereas ropivacaine 0.1% and 0.15% did not,
      and it was associated with fewer motor effects.

PMID- 16428532
TI  - Desflurane anesthesia after sevoflurane inhaled induction reduces severity of
      emergence agitation in children undergoing minor ear-nose-throat surgery compared
      with sevoflurane induction and maintenance.
AB  - Emergence agitation may occur after general anesthesia with volatile anesthetics
      in children. We designed this study to examine the emergence behavior of children
      undergoing ear-nose-throat surgery after sevoflurane induction and desflurane
      maintenance versus both sevoflurane induction and maintenance using a recently
      published Pediatric Anesthesia Emergence Delirium (PAED) scale. In 38
      premedicated children aged 12 mo to 7 yr mask induction with sevoflurane was
      performed and they were randomly assigned to receive either sevoflurane (n = 19)
      or desflurane (n = 19) for maintenance of general anesthesia. Time to tracheal
      extubation, modified Aldrete score, emergence behavior, recovery complications,
      and pain scores were assessed. The PAED scale showed a significant advantage for
      desflurane (6 [0-15] versus 12 [2-20], maximum total score of 20 for severe
      agitation). Time to extubation was significantly shorter with desflurane than
      with sevoflurane (5.4 +/- 1.4 versus 13.4 +/- 1.8 min). The modified Aldrete
      score on arrival in the postanesthesia care unit (PACU) was significantly lower
      in children receiving sevoflurane for maintenance. Time to discharge from PACU to
      normal ward and the incidence of adverse effects were not significantly different
      between the groups. In conclusion, the use of desflurane for maintenance of
      anesthesia after sevoflurane induction in children is associated with less severe
      emergence agitation and faster emergence times.

PMID- 16428533
TI  - The size 1(1/2) ProSeal laryngeal mask airway in infants: a randomized, crossover
      investigation with the Classic laryngeal mask airway.
AB  - Many problems with the Classic laryngeal mask airway (CLMA) in infants are
      believed to be related to its inadequate cuff design. One of the main limitations
      of the CLMA is that the resulting low-pressure seal can be inadequate for
      positive pressure ventilation (PPV). The ProSeal LMA (PLMA), a new laryngeal mask
      airway with a modified cuff, has been shown to form a more effective seal than
      the CLMA in children. The first infant size PLMA, size 1(1/2), became available
      recently. We studied 30 anesthetized, nonparalyzed infants aged 15 mo (2-30 mo)
      and weighing 9 kg (5-12 kg). The CLMA and PLMA were inserted in random order into
      each patient. Airway leak pressure and maximum tidal volume were measured. Ease
      of insertion, quality of initial airway, and fiberoptic position were also
      determined. Gastric tube placement was assessed for the PLMA. The mean airway
      leak pressure in neutral head position (26.7 versus 18.9 cm H2O), maximum flexion
      (35.6 versus 28.2 cm H2O), and the mean maximum tidal volume (312 versus 260 mL)
      were significantly higher for the PLMA (P < 0.01). Air entered the stomach in
      eight patients with the CLMA but did not with the PLMA. Gastric tube placement
      was possible in all but one patient. In three patients, the use of the PLMA led
      to some degree of clinically relevant compression of the larynx. The size 1(1/2)
      PLMA seems to be a more suitable device for airway maintenance in infants than
      the same size CLMA. The ability to insert a gastric tube at the same time, and a
      significantly higher airway leak pressure than with the CLMA, may have important
      implications for its use for PPV in infants.

PMID- 16428534
TI  - A comparison of a needle-free injection system for local anesthesia versus EMLA
      for intravenous catheter insertion in the pediatric patient.
AB  - Placement of IV catheters is a painful and stressful procedure for children. J
      Tip is a needle-less Food and Drug Administration approved injection system that
      can be used for delivery of local anesthetic before IV cannulation. In this
      study, we compared the effectiveness of J-Tip versus eutectic mixture of local
      anesthetics (EMLA) to facilitate IV cannulation and provide adequate analgesia
      before IV placement. Children 7-19 years of age (n = 116) were randomized to
      receive 0.25 mL of 1% buffered lidocaine with J-Tip (n = 57) or 2.5 g of EMLA (n
      = 59) before IV cannulation. Measurements of success of cannulation (number of
      attempts for IV placement) and pain (0-10 visual analog scale) at application of
      local anesthetic and at cannulation were performed. There was a significant (P =
      0.0001) difference in pain ratings during IV cannulation between EMLA (median =
      3) and the J-Tip (median = 0). Eighty-four percent of patients reported no pain
      at the time of J-Tip lidocaine application compared to 61% in the EMLA group at
      the time of dressing removal (P = 0.004). We did not find differences in the
      number of attempts for IV cannulation. J-Tip application of 1% buffered lidocaine
      before IV cannulation is not painful and has better anesthetic effectiveness
      compared with EMLA.

PMID- 16428535
TI  - Residual gastric fluid volume and chewing gum before surgery.
AB  - In this study we sought to determine if chewing gum preoperatively increases
      gastric fluid volume (GFV) and changes gastric acidity. Children, 5-17 yr old,
      were randomized to one of three groups: a control group that was not given any
      gum, a group that was given sugarless bubble gum, and a group that was given
      sugared bubble gum. Patients in the two gum groups were instructed to chew their
      gum for a period of 30 min. After induction of anesthesia and tracheal
      intubation, the stomach was suctioned with a salem sump orogastric tube. We found
      that children who did not chew gum had significantly smaller GFV as compared with
      children who chewed sugared and sugarless gum (0.35 [0.2-0.5] mL/kg versus 0.88
      [0.6-1.4] mL/kg versus 0.69 [0.4-1.6] mL/kg; P = 0.0001). Children who did not
      chew gum also had a significantly lower gastric fluid pH as compared with
      children chewing sugared and sugarless gum (geometric mean, 1.91 versus 2.25
      versus 2.19; P = 0.007). We conclude that children who present for surgery while
      chewing gum have significantly larger GFV and higher pH.

PMID- 16428536
TI  - Methylprednisolone reduces pain, emesis, and fatigue after breast augmentation
      surgery: a single-dose, randomized, parallel-group study with methylprednisolone
      125 mg, parecoxib 40 mg, and placebo.
AB  - We compared methylprednisolone 125 mg IV (n = 68) and parecoxib 40 mg IV (n = 68)
      with placebo (n = 68) given before breast augmentation surgery in a randomized,
      double-blind parallel group study. Surgery was performed under local anesthesia
      combined with propofol/fentanyl sedation. Methylprednisolone and parecoxib
      decreased pain at rest and dynamic pain intensity from 1 to 6 h after surgery
      compared with placebo (mean summed pain intensity(1-6 h): methylprednisolone
      [17.25; 95% confidence interval [CI], 14.85-19.65] versus placebo [21.7; 95% CI,
      19.3-24.1]; P < 0.03; parecoxib [15.25; 95% CI, 13.25-17.25] versus placebo; P <
      0.001; mean summed dynamic pain intensity(1-6 h): methylprednisolone [22.7; 95%
      CI, 20.1-23.3] versus placebo [28.4; 95% CI, 26.0-30.8]; P < 0.01; parecoxib
      [20.9; 95% CI, 18.6-23.2] versus placebo; P < 0.001). Both rescue drug
      consumption and actual pain (all observations before and after rescue) during the
      first 6 h were similar in the two active drug groups and significantly reduced
      compared with placebo. Using a composite score of actual pain intensity and
      rescue analgesic use, the active drugs were significantly superior to placebo (P
      < 0.001 for both active drugs). Postoperative nausea and vomiting was reduced
      after methylprednisolone administration (incidence, 30%), but not after parecoxib
      (incidence, 37%), during the first 24 h compared with placebo (incidence, 60%; P
      < 0.001). Fatigue was reduced by methylprednisolone (incidence, 44%), but not by
      parecoxib (incidence, 59%), compared with placebo (incidence, 66%; P < 0.05). In
      conclusion, methylprednisolone 125 mg IV given before breast augmentation surgery
      had analgesic and rescue analgesic-sparing effects comparable with those of
      parecoxib 40 mg IV. Methylprednisolone, but not parecoxib, reduced nausea,
      vomiting, and fatigue.

PMID- 16428537
TI  - Postoperative residual paralysis in outpatients versus inpatients.
AB  - Postoperative residual paralysis is an important complication of the use of
      neuromuscular blocking drugs. In this prospective study, the incidence of
      residual paralysis detected as a train-of-four response <90% was less frequent in
      surgical outpatients (38%) than inpatients (47%) (P = 0.001). This might have
      been the result of the more frequent use of mivacurium for outpatients. Before
      undertaking tracheal extubation, the anesthesiologists had applied clinical
      criteria (outpatients, 49%; inpatients, 45%), pharmacological reversal (26%,
      25%), neuromuscular transmission monitoring (12%, 11%), or a combination of
      these. None of these measures seemed to reduce the incidence of residual
      paralysis except for quantitative train-of-four monitoring. Postoperatively,
      eight individual clinical tests or a sum of these tests were also unable to
      predict residual paralysis by train-of-four. Although the incidence of residual
      paralysis was less frequent in surgical outpatients, predictive criteria were not
      evident.

PMID- 16428538
TI  - The performance of a target-controlled infusion of propofol in combination with
      remifentanil: a clinical investigation with two propofol formulations.
AB  - Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an
      IV drug to facilitate safe and reliable administration. In this clinical study we
      investigated the performance of propofol TCI in combination with remifentanil.
      Fifty-four adult patients scheduled for general surgery lasting longer than 1 h
      received a combined TCI of propofol (Marsh parameter set; propofol randomly
      either dissolved with long- or middle-/long-chain triglycerides) and
      remifentanil. Arterial propofol plasma concentrations and hemodynamic and derived
      electroencephalogram variables were determined at various stages before, during,
      and after surgery. Measured propofol plasma concentrations exceeded the predicted
      values by 59%, and 48% when recalculated with the Schnider parameter set.
      Pharmacokinetic population analysis showed a small central volume of distribution
      (3.55 L) and reduced clearance (1.31 L/min) for propofol. ASA status and sex were
      the only variables that had a significant influence on propofol pharmacokinetics.
      In a second step, a new pharmacokinetic variable set for propofol was determined
      in the first 27 patients. Post hoc performance analysis of the remaining 27
      patients showed improved accuracy using the new variable set. Our results show
      that when remifentanil and propofol are combined, the Marsh and Schnider
      parameter sets systematically underestimate propofol plasma concentrations.
      Presented, in part, at the Annual Meeting of the European Society of
      Anesthesiologists, Amsterdam, The Netherlands, June 1, 1999, and the Annual
      Meeting of the American Society of Anesthesiologists, Dallas, Texas, October 12,
      1999.

PMID- 16428539
TI  - The dose of succinylcholine in morbid obesity.
AB  - The appropriate dose of succinylcholine (SCH) in morbidly obese patients is
      unknown. We studied 45 morbidly obese (body mass index >40 kg/m2) adults
      scheduled for gastric bypass surgery. The response to ulnar nerve stimulation of
      the adductor pollicis muscle at the wrist was recorded using the TOF-Watch SX
      acceleromyograph. In a randomized double-blind fashion, patients were assigned to
      one of three study groups. In Group I, patients received SCH 1 mg/kg ideal body
      weight, in Group II 1 mg/kg lean body weight, and in Group III 1 mg/kg total body
      weight. After SCH administration, endotracheal intubating conditions were scored.
      The recovery from neuromuscular block was recorded for 20 min. There was no
      difference in the onset time of maximum neuromuscular blockade among groups, but
      maximum block was significantly less in Group I. The recovery intervals were
      significantly shorter in Groups I and II. In one third of the patients in Group
      I, intubating conditions were rated poor, whereas no patient in Group III had
      poor intubating conditions. Our study demonstrates that for complete
      neuromuscular paralysis and predictable laryngoscopy conditions, SCH 1 mg/kg
      total body weight is recommended.

PMID- 16428540
TI  - The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid
      agonist, and ketorolac.
AB  - Combinations of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids are
      widespread in the management of pain, allowing better analgesia with reduced side
      effects. Cannabinoids are promising analgesic drugs that have pharmacological
      properties similar to those of opioids. However, the beneficial effects of
      cannabinoids for pain treatment are counterbalanced by their psychotomimetic side
      effects. We designed the present study to evaluate the antinociceptive
      interaction between cannabinoids and NSAIDs in mice, using the acetic acid
      induced writhing test and tail-flick test. Interactions were analyzed using
      isobolographic analysis. WIN 55,212-2, a cannabinoid agonist, and the NSAID
      ketorolac, either alone or in combination, produced dose-dependent
      antinociception in the writhing test. Isobolographic analysis showed additive
      interactions between WIN 55,212-2 and ketorolac when they were coadministered
      systemically. Ketorolac is inactive in the radiant heat tail-flick test in which
      WIN 55,212-2 was active. Ketorolac did not influence WIN 55,212-2-induced
      antinociception in the tail-flick test. This study demonstrated an additive
      antinociceptive interaction between WIN 55,212-2 and ketorolac in an inflammatory
      visceral pain model. The combination of cannabinoids and NSAIDs may have utility
      in the pharmacotherapy of pain.

PMID- 16428541
TI  - Dexmedetomidine-induced decreases in accumbal dopamine in the rat are partly
      mediated via the locus coeruleus.
AB  - We have demonstrated previously that the systemic administration of the selective
      alpha2-adrenoceptor agonist dexmedetomidine (Dex) decreases extracellular
      dopamine (DA) levels in the rat nucleus accumbens (NAcc). Because the locus
      ceruleus (LC) is a noradrenergic center linked to several of the pharmacological
      effects of Dex, we investigated the role of the LC in Dex-induced modulation of
      accumbal DA. Microdialysis probes were implanted in the NAcc and LC of Sprague
      Dawley rats, and Dex 5 mM (Dex-High, n = 6), Dex 0.5 mM (Dex-Mid, n = 5), Dex 5
      microM (Dex-Low, n = 6), or artificial cerebrospinal fluid (control, n = 5) was
      administered in the LC via retrograde microdialysis for 45 min. Extracellular DA
      levels were continuously measured in the NAcc dialysates using high-performance
      liquid chromatography coupled to electrochemical detection. Dex produced
      significant decreases in extracellular DA in the NAcc. Accumbal DA decreased
      maximally to 68.9% +/- 8.8%, 75.1% +/- 6.5%, and 77.04% +/- 12.8% of baseline in
      the Dex-High, Dex-Mid, and Dex-Low groups, respectively. No significant decrease
      in extracellular DA was observed in the control group. The coadministration of
      the highly selective alpha2-adrenoceptor antagonist (n = 6) RS 79948 20 mM
      prevented the Dex-induced decrease in accumbal DA. These data suggest that the LC
      plays a role in Dex-induced modulation of mesolimbic DA and support the
      hypothesis that noradrenergic systems can regulate remote dopaminergic sites in
      the central nervous system.

PMID- 16428542
TI  - The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated
      by the alpha2A-adrenoceptor subtype.
AB  - We performed the current study in mice lacking individual alpha2-adrenoceptor
      subtypes to elucidate the contribution of alpha(2)-adrenoceptor subtypes to the
      neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic
      brain injury. On postnatal Day 5, wild-type mice and mice lacking alpha2A
      adrenoceptor (alpha2A-KO) or alpha2C-adrenoceptor subtypes (alpha2C-KO) were
      randomly assigned to receive dexmedetomidine (3 microg/kg) or phosphate-buffered
      saline intraperitoneally. Thirty minutes after the intraperitoneal injection, the
      glutamatergic agonist ibotenate (10 microg) was intracerebrally injected,
      producing transcortical necrosis and white matter lesions that mimic perinatal
      human hypoxic-like lesions. Quantification of the lesions was performed on
      postnatal Day 10 by histopathologic examination. Dexmedetomidine reduced mean
      lesion size in the cortex of wild-type mice and alpha2C-KO mice by 44% and 49%,
      respectively. Ibotenate-induced white matter lesions were reduced by 71% (wild
      type mice) and 75% (alpha2C-KO mice) after pretreatment with dexmedetomidine. In
      contrast, in alpha2A-KO mice, dexmedetomidine did not protect against the
      cortical excitotoxic insult, and white matter lesions were even more pronounced
      (82% increase of mean lesion size). Dexmedetomidine provides potent
      neuroprotection in a model of perinatal excitotoxic brain damage. This effect was
      completely abolished in alpha2A-KO mice, suggesting that the neuroprotective
      effect is mediated via the alpha2A-adrenoceptor subtype.

PMID- 16428543
TI  - Local anesthetics suppress nerve growth factor-mediated neurite outgrowth by
      inhibition of tyrosine kinase activity of TrkA.
AB  - Local anesthetics (LAs) suppress sympathetic sprouting, which correlates with
      neuropathic pain. However, the precise mechanism of the suppression is unknown.
      Nerve growth factor (NGF) contributes to the sympathetic sprouting, and NGF
      signaling starts with NGF-stimulated autophosphorylation of TrkA, which is a high
      affinity receptor of NGF. We examined the effects of lidocaine, bupivacaine, and
      procaine on NGF signaling under suppression of NGF-stimulated neurite outgrowth
      in PC12 cells, which is a cellular model of sympathetic sprouting. To investigate
      the effect of these LAs on NGF-mediated neurite outgrowth of PC12 cells, cells
      were incubated with 40, 400, and 4000 microM of each LA. The effect of LAs on NGF
      stimulated TrkA activity was examined to analyze autophosphorylation of TrkA
      using immunoprecipitation and immunoblotting. Cytotoxic effects of LAs on PC12
      cells were also assessed by lactate dehydrogenase release and by propidium iodide
      staining. Lidocaine (400 microM), bupivacaine (40 and 400 microM), or procaine
      (4000 microM) suppressed either neurite outgrowth or autophosphorylation
      significantly without cytotoxicity. The inhibition of NGF-stimulated tyrosine
      kinase activity of TrkA might be involved in the mechanisms of suppression of
      neurite outgrowth induced by LAs.

PMID- 16428544
TI  - The dose-response relationship and regional distribution of lactate after
      intramuscular injection of halothane and caffeine in malignant hyperthermia
      susceptible pigs.
AB  - We hypothesized that IM halothane and caffeine injection increases local lactate
      concentration dose-dependently in malignant hyperthermia-susceptible (MHS) and
      nonsusceptible (MHN) pigs and that the hypermetabolic reaction measured by
      regional distribution of lactate and carbon dioxide is limited to a small muscle
      volume. Microdialysis probes were placed in the hindlimbs of 7 MHS and 7 MHN pigs
      and perfused with Ringer's solution. After equilibration, boluses of increasing
      halothane and caffeine concentrations were injected. For the second hypothesis
      regarding regional distribution, microdialysis probes were positioned in 7 MHS
      and 6 MHN pigs at the injection site for halothane and caffeine and at a distance
      of 10 mm and 25 mm. Lactate was measured in the dialysate by spectrophotometry.
      In addition, PCO2 was measured in the halothane experiments. Halothane and
      caffeine increased IM lactate dose-dependently in MHS pigs significantly more
      than in MHN pigs. Lactate and PCO2 were increased only at the injection site but
      not at 10 mm and 25 mm distance. MH susceptibility leads to a leftward shift of
      the dose-response curve for IM lactate after local injection of halothane and
      caffeine. The increase of lactate and carbon dioxide levels after local MH
      trigger injection is limited to a small area around the probe.

PMID- 16428545
TI  - The effects of local anesthetics on bile flow, potassium equilibrium and oxygen
      consumption in the perfused rat liver.
AB  - Amide local anesthetics mainly undergo hepatic metabolism. Specific applications,
      such as catheter application for long-term pain therapy, may result in large
      plasma concentrations. As it is unknown whether local anesthetics influence liver
      function, we examined the influence of lidocaine, bupivacaine, and ropivacaine in
      concentrations of 1 and 10 microg/mL on the metabolic activity of the perfused
      rat liver. At the large concentrations, all three local anesthetics caused an
      immediate increase of oxygen consumption. Bupivacaine and ropivacaine also
      transiently reduced potassium release. All drugs increased bile flow; this
      choleretic effect was also significant for bupivacaine and lidocaine in smaller
      concentrations. In the smaller concentration, only lidocaine significantly
      increased oxygen consumption. No significant changes in hepatic venous pH were
      observed. The results show that acute administration of all three local
      anesthetics results in significant changes of functional variables of the liver.
      The observed effects appear to result from mitochondrial uncoupling, uptake of
      the drugs, biliary secretion of their metabolites, and from inhibition of
      potassium channels. The data provide no evidence that these acute changes may
      result in enduring postoperative disturbances of liver function, such as
      cholestasis or jaundice.

PMID- 16428546
TI  - Wireless continuous arterial blood pressure monitoring during surgery: a pilot
      study.
AB  - Patient monitoring devices supporting wireless transmission can facilitate
      transport and ambulation of patients in hospitals. To replace wired sensors with
      wireless sensors, the accuracy and resistance to interference of the wireless
      sensors have to be documented. We compared the performance of a wireless arterial
      blood pressure biomedical sensor prototype with standard wired sensors in a
      clinical setting. Four patients undergoing laparoscopic abdominal surgery were
      recruited for testing of the device. Lines to a wireless arterial blood pressure
      sensor and standard wired sensor were connected to the same arterial cannula
      inserted in the right radial artery. Data from both systems were logged for
      postprocedure statistical comparison. During the procedure, 13 other electric
      devices were used, either continuously or intermittently. A sample-by-sample
      comparison was performed for both wired and wireless data. Statistical tests
      showed mean difference of 0.71, standard deviation of 0.14, and confidence
      interval of -1.28 to 1.56), indicating no significant electromagnetic
      interference on invasive arterial blood pressure monitoring caused by biomedical
      devices used during surgery. The wireless pressure biomedical sensor with
      Bluetooth wireless transmission of signals did not interfere with biomedical
      devices used in the operating room or vice versa.

PMID- 16428547
TI  - An accuracy evaluation of the T-Line Tensymeter (continuous noninvasive blood
      pressure management device) versus conventional invasive radial artery monitoring
      in surgical patients.
AB  - Continuous beat-to-beat arterial blood pressure (BP) monitoring with a
      simultaneous arterial waveform display is typically achieved with an invasive
      arterial catheter. We evaluated a noninvasive device, the T-Line Tensymeter, that
      provides a calibrated arterial pressure waveform from which continuous BP
      measurements and heart rate may be computed by either a bedside host monitor or
      the tensymeter device itself. In 25 patients given general anesthesia, we
      measured systolic, mean, and diastolic BPs via the tensymeter and compared these
      measurements with those obtained from the contralateral radial artery catheter.
      Data were analyzed using the Bland Altman test to determine agreement between the
      two systems. The mean +/- sd bias and precision (mm Hg) were as follows: 1.7 +/-
      7.0 and 5.7 +/- 4.4 for systolic BP; 2.3 +/- 6.9 and 5.7 +/- 4.5 for diastolic
      BP; and 1.7 +/- 5.3 and 4.0 +/- 4.8 for mean BP. Noninvasive pressures from the
      tensymeter-produced arterial waveform agreed with simultaneous contralateral BPs
      measured from arterial catheters within an acceptable clinical range for a
      limited population of surgical patients studied over a systolic arterial BP range
      from 41 to 189 mm Hg without significant temporal performance degradation. The
      tensymeter may enable physicians to circumvent arterial cannulation in certain
      circumstances (such as with low- or intermediate-risk procedures) on patients
      when beat-to-beat BP measurement is desirable.

PMID- 16428548
TI  - The OxyArm: a supplemental oxygen delivery device.
AB  - Facemasks and nasal cannulae are used to provide supplemental oxygen to patients
      in the postoperative period after general anesthesia. These devices are
      associated with several patient complications, including aspiration, hypercarbia,
      and mechanical trauma. A new device, the OxyArm, is designed to eliminate these
      problems. It is an "open oxygen" system that does not require physical contact
      with the patient's face. In this clinical study we evaluated the OxyArm in the
      immediate postoperative period. Sixty patients received supplemental oxygen via
      the OxyArm for the first 8 min after tracheal extubation after general
      anesthesia. Oxygen saturation values were continuously recorded during 3 4-min
      time periods: 1) while breathing oxygen through an endotracheal tube before
      tracheal extubation, 2) while breathing oxygen delivered by the OxyArm at 4 L/min
      4 min after tracheal extubation, and 3) while breathing oxygen delivered by the
      OxyArm at 2 L/min 8 min after tracheal extubation. There were no significant
      differences in oxygen saturation among the three time periods and no patient
      experienced an oxygen desaturation event less than 88%. Patients and clinicians
      praised the OxyArm for its comfort and ease of use, allowing nursing facial care
      without interrupting oxygen therapy. We conclude that the OxyArm delivers
      adequate levels of oxygen for most patients during the early postoperative
      period.

PMID- 16428549
TI  - The auditory middle latency response, evoked using maximum length sequences and
      chirps, as an indicator of adequacy of anesthesia.
AB  - The auditory evoked potential known as the middle latency response (MLR), evoked
      with regular click stimulation at around 5 Hz, has been suggested as an indicator
      of adequacy of anesthesia. The MLR is a very small signal embedded in high levels
      of background noise, so it can take a long time to acquire. However, using a
      stimulus paradigm of chirps presented in a maximum length sequence, the
      acquisition of the MLR can be improved compared to using conventional click
      stimulation. In this pilot study, we investigated this new technique in a
      clinical environment. Significant changes in MLR amplitude, but not latency, were
      measured for six of seven subjects in association with changes in responsiveness
      to command using the isolated forearm technique. The absence of any latency shift
      differs from other studies of the MLR during anesthesia and highlights the
      limited understanding of the relationship between anesthesia and the MLR.

PMID- 16428551
TI  - Perioperative nimodipine and postoperative analgesia.
AB  - There is experimental evidence that nimodipine, an L-type dihydropiridine calcium
      channel blocker with relatively high blood-brain barrier penetration, enhances
      the antinociceptive properties of morphine. We tested the hypothesis that oral
      nimodipine taken preoperatively and 6 hourly for 48 h postoperatively would
      reduce visual analog scale pain scores and morphine consumption in morphine-naive
      patients with acute postoperative pain. Forty patients undergoing total knee
      replacement surgery (age 70 +/- 7 yr, 28 male) were randomized by computer
      generated numbers to receive capsules containing either nimodipine 30 mg or
      placebo in a double-blind study design. All patients received 3 capsules
      (nimodipine 90 mg or placebo) 1-2 h before induction of anesthesia followed by
      oral nimodipine 30 mg or placebo 6 hourly for 48 hours postoperatively. Spinal
      anesthesia was induced with hyperbaric bupivacaine 0.5% (2.4-3.0 mL) and fluids
      and ephedrine were given at the discretion of the anesthesiologist. Morphine
      patient-controlled analgesia (PCA, bolus 1 mg, lockout 5 min) was given for
      postoperative analgesia. Primary outcome measures were visual analog pain scores
      at rest and on moving (sitting forward) and PCA morphine consumption. Morphine
      consumption was significantly larger in nimodipine patients at 12 h (39 +/- 18
      versus 29 +/- 15; P = 0.04), 24 h (62 +/- 23 versus 45 +/- 24; P = 0.02), and 48
      h (88 +/- 34 versus 61 +/- 27; P = 0.01). There were no significant differences
      in pain scores at rest or moving or in time to first use of morphine analgesia.
      This study has demonstrated increased morphine consumption after 12 h in
      postoperative patients receiving nimodipine, suggesting that, in patients
      undergoing knee replacement surgery, it has no adjunctive analgesic effect and
      may actually inhibit the analgesic effect of morphine.

PMID- 16428550
TI  - The incidence of complex regional pain syndrome after fasciectomy for Dupuytren's
      contracture: a prospective observational study of four anesthetic techniques.
AB  - The development of complex regional pain syndrome (CRPS) is not an uncommon
      complication after Dupuytren's surgery. Despite increasing research interest,
      little is known regarding which patients are at increased risk for developing
      CRPS and what is the optimal perioperative treatment strategy for preventing the
      occurrence of this disease after surgery. We prospectively evaluated the use of
      four anesthetic techniques (general anesthesia, axillary block, and IV regional
      anesthesia [IVRA] with lidocaine with or without clonidine) for patients
      undergoing fasciectomy for Dupuytren's contracture. All patients were followed in
      the Pain Management Center at 1, 3, and 12 mo postoperatively by a blinded
      physician to evaluate the presence of CRPS. Significantly (P < 0.01) more
      patients developed postoperative CRPS in the general anesthesia group (n = 25;
      24%) and the IVRA lidocaine group (n = 12; 25%) compared with either the axillary
      block group (n = 5; 5%) or the IVRA lidocaine and clonidine group (n = 3; 6%). We
      conclude that axillary block or IVRA with clonidine offers a significant
      advantage for decreasing the incidence of CRPS compared with either IVRA with
      lidocaine alone or general anesthesia for patients undergoing Dupuytren's
      surgery.

PMID- 16428552
TI  - A lack of antinociceptive or antiinflammatory effect of botulinum toxin A in an
      inflammatory human pain model.
AB  - Several in vitro and in vivo investigations have shown that botulinum toxin A
      (BoNT/A) can inhibit the release of substance P and excitatory amino acids.
      Recently, a marked antinociceptive effect of BoNT/A and inhibition of glutamate
      release was observed in an animal pain model with inflammatory sensitization. In
      the present study, we tested the antiinflammatory and antihyperalgetic effect of
      BoNT/A in a well-characterized human inflammatory pain model. Using a randomized,
      double-blind, paired study design, we compared the effects of 100 mouse units of
      BoNT/A versus pure saline. Thermal and mechanical pain testings and superficial
      skin blood flow measurements were performed at baseline, at 48 h (in normal
      skin), and at 72 h (in inflamed skin) thereafter. Ultraviolet B irradiation
      resulted in a local inflammation with significant primary and secondary
      hyperalgesia. However, despite the evidence of efficacy on sudomotor function,
      BoNT/A had no effect on pain measures in either normal or inflamed skin. Signs of
      inflammation and primary and secondary hyperalgesia were found to be unaffected
      by BoNT. We have confirmed that BoNT/A has no direct effect on acute,
      noninflammatory pain. Furthermore, despite highly promising data from animal
      research, we have not observed antiinflammatory or antinociceptive effects of
      BoNT/A in human inflammatory pain.

PMID- 16428553
TI  - Trends in the financial status of United States anesthesiology training programs:
      2000 to 2004.
AB  - The decrease in resident applicants for United States (U.S.) anesthesiology
      training programs in the mid-1990s has resulted in a national anesthesiologist
      shortage. This shortage has been associated with increased salaries for
      anesthesiologists in academic institutions. Salary increases have placed the
      financial condition of academic training departments in jeopardy, requiring
      increasing support from their institutions. In the year 2000, a nationwide survey
      of the financial status of the U.S. anesthesiology training programs was
      conducted. Follow-up surveys have been conducted each year thereafter. We present
      the results of the fifth such survey. One-hundred-twenty-eight departments were
      surveyed, with a response rate of 73%. The average department employs 45 faculty
      and 81% of those departments have an average of 3.3 open positions. Of the 91% of
      departments who employ Certified Registered Nurse Anesthetists (CRNAs) (an
      average of 25 CRNAs/department), 73% have an average of 4.2 open CRNA positions.
      The average department received 3,787,835 dollars (or 97,621 dollars/faculty) in
      institutional support, which is an increase over the 2003 amount of 85,607
      dollars/faculty. In 36.6% of the departments a portion of these support dollars
      (1,888,111 dollars) was provided to support CRNA salaries. Therefore, the support
      to departments for faculty averaged 81,696 dollars/faculty, after the CRNA
      dollars were removed. Faculty academic time averaged 16% (where 20% is 1 day/wk)
      and departments billed an average of 11,954 anesthesia units/faculty/yr. These
      results demonstrate a continued shortage of anesthesiology faculty and continued
      institutional support to keep these training programs financially viable.

PMID- 16428554
TI  - Spinal versus general anesthesia for orthopedic surgery: anesthesia drug and
      supply costs.
AB  - Total hip or knee replacement surgeries are common orthopedic interventions that
      can be performed with spinal anesthesia (SA) or general anesthesia (GA). No study
      has investigated the economic aspects associated with the two anesthetic
      techniques for this common surgery. We randomized 40 patients to receive either
      SA or GA and analyzed the drug and supply costs for anesthesia und recovery.
      Anesthesia-related times, hemodynamic variables, and pain scores were also
      recorded. Total costs per case without personnel costs were almost half in the SA
      group compared with the GA group; this was a result of less cost for anesthesia
      (P < 0.01) and for recovery (P < 0.05). This finding was supported by a
      sensitivity analysis. There were no relevant differences regarding anesthesia
      related times. Patients in the GA group were admitted to the postanesthesia care
      unit with a higher pain score and needed more analgesics than patients in the SA
      group (both P < 0.01). We conclude that SA is a more cost-effective alternative
      to GA in patients undergoing hip or knee replacement, as it is associated with
      lower fixed and variable costs. Moreover, SA seems to be more effective, as
      patients in the SA group showed lower postoperative pain scores during their stay
      in the postanesthesia care unit.

PMID- 16428555
TI  - An assessment of a point-of-care information system for the anesthesia provider
      in simulated malignant hyperthermia crisis.
AB  - In this prospective, controlled study we compared the ability of anesthesia
      residents to diagnose and treat a simulated malignant hyperthermia (MH) scenario
      with and without the ability to use the On-Line Electronic Help (OLEH)
      information system or any other written guidelines. The OLEH is a point-of-care
      information system for the anesthesia provider in the operating room. The score
      for MH treatment after diagnosis based on clinical actions was significantly
      higher (P = 0.018) in the OLEH-user group (21.5 +/- 4.9) compared with a control
      group (15.5 +/- 7.6). This study demonstrates the possible value of a point-of
      care information system in patient care; however, the significance of the results
      may be limited by the participants' anticipation of an acute event during
      training requiring the use of the OLEH.

PMID- 16428556
TI  - Everybody on the phone?

PMID- 16428557
TI  - Communication in critical care environments: mobile telephones improve patient
      care.
AB  - Most hospital policies prohibiting the use of wireless devices cite reports of
      disruption of medical equipment by cellular telephones. There have been no
      studies to determine whether mobile telephones may have a beneficial impact on
      safety. At the 2003 meeting of the American Society of Anesthesiologists 7878
      surveys were distributed to attendees. The five-question survey polled
      anesthesiologists regarding modes of communication used in the operating
      room/intensive care unit and experience with communications delays and medical
      errors. Survey reliability was verified using test-retest analysis and proportion
      agreement in a convenience sample of 17 anesthesiologists. Four-thousand-eighteen
      responses were received. The test-retest reliability of the survey instrument was
      excellent (Kappa = 0.75; 95% confidence interval, 0.56-0.94). Sixty-five percent
      of surveyed anesthesiologists reported using pagers as their primary mode of
      communications, whereas only 17% used cellular telephones. Forty-five percent of
      respondents who use pagers reported delays in communications compared with 31% of
      cellular telephone users. Cellular telephone use by anesthesiologists is
      associated with a reduction in the risk of medical error or injury resulting from
      communication delay (relative risk = 0.78; 95% confidence interval, 0.6234
      0.9649). The small risks of electromagnetic interference between mobile
      telephones and medical devices should be weighed against the potential benefits
      of improved communication.

PMID- 16428558
TI  - Epinephrine increases mortality after brief asphyxial cardiac arrest in an in
      vivo rat model.
AB  - Epinephrine may be detrimental in cardiac arrest. In this laboratory study we
      sought to characterize the effect of epinephrine and concomitant calcium channel
      blockade on postresuscitation myocardial performance after brief asphyxial
      cardiac arrest. Anesthesized rats were disconnected from mechanical ventilation,
      resulting in cardiac arrest. Resuscitation was attempted after 1 min with
      mechanical ventilation, oxygen, chest compressions, and IV medication. In
      experimental series 1 and 2, animals were allocated to 10 or 30 microg/kg
      epinephrine or 0.9% saline. In series 3, animals received 30 microg/kg of
      epinephrine and were randomized to 0.1 mg/kg of verapamil or to 0.9% saline. In
      series 1 and 3, left ventricular function was assessed using transthoracic
      echocardiography. In series 2, left atrial pressure was measured. Epinephrine was
      associated with increased mortality (0/8 [0%] in controls, 4/12 [33.3%] in 10
      microg/kg animals, and 16/22 [72.8%] in 30 microg/kg animals; P < 0.05),
      hypertension (P < 0.001), tachycardia (P = 0.004), early transient left atrial
      hypertension, and dose-related reduction in left ventricular end diastolic
      diameter (P < 0.05). Verapamil prevented mortality associated with large-dose
      epinephrine (0% versus 100%) and attenuated early diastolic dysfunction and
      postresuscitation hypertension (P = 0.001) without systolic dysfunction.
      Epinephrine appears to be harmful in the setting of brief cardiac arrest after
      asphyxia.

PMID- 16428559
TI  - Hypoglycemia and cardiac arrest in a critically ill patient on strict glycemic
      control.
AB  - Glycemic control in critically ill patients has become a subject of considerable
      interest since the publication of studies showing reduced morbidity and mortality
      in patients when blood glucose was maintained within a relatively low and narrow
      range (4.4 to 6.1 mM/L). We describe a patient who developed cardiac asystole
      while being given a concentrated glucose solution to treat severe hypoglycemia
      after administration of insulin. The mechanism in this patient appears to be
      hyperkalemia from the rapid administration of a concentrated glucose solution.

PMID- 16428560
TI  - The effect of sevoflurane on dynamic cerebral blood flow autoregulation assessed
      by spectral and transfer function analysis.
AB  - Sevoflurane reduces autonomic neural control, which plays a significant role in
      cerebral autoregulation. Therefore, we hypothesized that sevoflurane influences
      cerebral autoregulation. We investigated the effects of sevoflurane on dynamic
      cerebral blood flow (CBF) autoregulation by using spectral and transfer function
      analysis between blood pressure variability and CBF velocity variability. Eleven
      healthy male subjects received 0.5%, 1.0%, and 1.5% sevoflurane via facemask.
      Dynamic cerebral autoregulation was evaluated by transfer function gain, phase,
      and coherence between CBF velocity in the middle cerebral artery measured by
      transcranial Doppler, and blood pressure in the radial artery. Coherence in the
      very low-frequency range (0.02-0.07 Hz) increased above 0.5 during administration
      of 0.5% and 1.0% sevoflurane. Transfer function gain in this frequency range
      (0.02-0.07 Hz), as an index of dynamic cerebral autoregulation, increased
      significantly with 0.5% and 1.0% sevoflurane. Transfer function gain and
      coherence in the low- and high-frequency ranges, however, remained unchanged
      during administration of sevoflurane. These results suggest that sevoflurane
      impairs dynamic cerebral autoregulation in the very-low-frequency range even with
      small concentrations, whereas dynamic cerebral autoregulation in the low- and
      high-frequency ranges remained unchanged.

PMID- 16428561
TI  - Cerebral autoregulation and CO2 reactivity in anterior and posterior cerebral
      circulation during sevoflurane anesthesia.
AB  - The purpose of the study was to compare cerebral autoregulation (CA) and CO2
      reactivity (CO2R) between the anterior and posterior circulation under
      sevoflurane anesthesia. We studied 9 adult ASA physical status I patients (22-47
      yr) scheduled for elective orthopedic surgery. Blood flow velocity in the middle
      cerebral artery (Vmca) and in the basilar artery (Vba) were measured using
      transcranial Doppler ultrasonography. For CA testing, arterial blood pressure was
      increased using phenylephrine infusion. CA was quantified with the autoregulatory
      index (ARI). CO2R was investigated at PaCO2 of 30 +/- 2.8 mm Hg, 39.4 +/- 2.6 mm
      Hg, and 48.7 +/- 2.8 mm Hg. Linear regression analysis was used for CO2R. We
      found ARI was preserved in both arteries: ARImca (middle cerebral artery) = 0.72
      +/- 0.2; ARIba (basilar artery) = 0.66 +/- 0.2; P = 0.5. With regard to CO2R,
      Vmca increased with slope of 1.7 cm/s/mm Hg PaCO2, Vba increased with slope of
      1.5 cm/s/mm Hg PaCO2; P = 0.83. Absolute Vmca was higher compared with Vba; P <
      0.05. We conclude that in healthy individuals under 0.5 MAC of sevoflurane and
      small-dose remifentanil: 1) mean flow velocities of BA are less than those of
      MCA; 2) autoregulation and CO2R are preserved in the basilar artery and are
      similar to those of MCA.

PMID- 16428562
TI  - Measuring hemoglobin oxygen saturation during graded hypoxic hypoxia in rat
      striatum.
AB  - We evaluated in vivo reflectance spectroscopy of visible light as a method to
      assess brain tissue hemoglobin oxygen saturation in rat striatum (SstrO2). Seven
      anesthetized and mechanically ventilated rats were subjected to incremental
      reduction in the fraction of inspired oxygen (Fio2): 0.35, 0.25, 0.15, 0.12, and
      0.10, followed by a reoxygenation period (Group 1). At each episode, local
      changes in SstrO2 and in cerebral blood flow (LCBF) were simultaneously
      determined in the two striatal regions, using reflectance spectroscopy and laser
      Doppler flowmetry, respectively. Another group of rats (Group 2, n = 6) was also
      studied to measure sagittal sinus blood hemoglobin saturation (SssO2) during
      graded hypoxic hypoxia. Corpus striatum exhibited a significant graded decrease
      in SstrO2, from 38% +/- 17% at Fio2 of 0.35 (control) to 16% +/- 10% at Fio2 of
      0.12 and to 13% +/- 7% at Fio2 of 0.10 (P < 0.05), with no difference between the
      two hemispheres. These local changes in SstrO2 were associated with a significant
      graded increase in LCBF: 161% +/- 26% of control values and 197% +/- 34% during
      these 2 hypoxic episodes, respectively (P < 0.05). All local changes were fully
      reversed during the reoxygenation period. In Group 2, SssO2 decreased from 38% +/
      8% at Fio2 of 0.35 (control) to 10% +/- 3% at Fio2 of 0.10, closely related to
      SstrO2 decreasing in hypoxia. This study shows that reflectance spectroscopy of
      the visible light in rat striatum could be a possible measure of continuous
      changes in SstrO2. SssO2 and LCBF measurements during graded hypoxic hypoxia
      indicate that changes in SstrO2 reflect primarily those in brain venous
      oxygenation.

PMID- 16428563
TI  - Vasodilation mediated by inward rectifier K+ channels in cerebral microvessels of
      hypertensive and normotensive rats.
AB  - Although inward rectifier K+ channels contribute to the regulation of cerebral
      circulation, dilation of cerebral microvasculature mediated by these channels has
      not been demonstrated in chronic hypertension. We designed the present study to
      examine the roles of inward rectifier K+ channels in the vasodilation produced by
      increased levels of extracellular K+ in cerebral parenchymal arterioles from
      hypertensive and normotensive rats. During constriction to prostaglandin F2alpha
      (5 x 10(-7) M), the arterioles within brain slices were evaluated using computer
      assisted microscopy. Potassium chloride (KCl) induced vasodilation in cerebral
      arterioles from normotensive (5-10 mM) and hypertensive (5-15 mM) rats, whereas
      an inward rectifier K+ channel antagonist barium chloride (BaCl2; 10(-5) M)
      completely abolished the vasodilation in both strains. In arterioles of
      hypertensive rats, vasodilator responses to KCl were augmented compared with
      those in normotensive rats. In contrast, the vasodilator responses induced by
      sodium nitroprusside (3 x 10(-8) to 3 x 10(-6) M) in these two strains were
      similar. These results suggest that in cerebral cortex parenchymal microvessels,
      inward rectifier K+ channels play a crucial role in vasodilation produced by
      extracellular K+ and that the dilation of cerebral arterioles via these channels
      is augmented in chronic hypertension.

PMID- 16428564
TI  - Combined spinal epidural causes higher level of block than equivalent single-shot
      spinal anesthesia in elective cesarean patients.
AB  - Combined spinal epidural (CSE) is an established technique for lower segment
      cesarean delivery. In this study we tested the hypothesis that the spinal block
      from a CSE technique results in a more extensive spread of local anesthetic in
      the subarachnoid space than the single-shot spinal (SSS) technique. We recruited
      30 ASA physical status I parturients admitted for elective lower segment cesarean
      delivery into our randomized, controlled, double-blind study. All patients
      intrathecally received 2 mL of 0.5% hyperbaric bupivacaine. The patients were
      randomized into one of the two groups using sealed opaque envelopes. Group S (n =
      15) received a SSS technique. Group CS (n = 15) received a CSE technique using
      loss of resistance to 2 mL of air, but the epidural catheter was not inserted
      after the intrathecal drug administration. The maximal sensory block achieved in
      group CS was statistically higher than that in Group S (median C6 interquartile
      range, C5 to C8 versus median T3, T2 to T4, P < 0.001). Time taken to reach
      maximal sensory block was significantly longer in group CS. There were no
      differences in the time taken for the block to recede to T10, hemodynamic
      profile, or side effects. In conclusion, the CSE technique without placing an
      epidural catheter or administering epidural medication resulted in a
      significantly higher level of sensory block when compared with the SSS technique
      when the same dose of local anesthetic was given intrathecally.

PMID- 16428565
TI  - Transcutaneous acupoint electrical stimulation with the ReliefBand for the
      prevention of nausea and vomiting during and after cesarean delivery under spinal
      anesthesia.
AB  - We randomized 94 patients undergoing cesarean delivery with spinal anesthesia to
      receive transcutaneous acupoint electrical stimulation using the ReliefBand at
      the P6 point (active group) or an active ReliefBand applied to the dorsum of the
      wrist (sham control group). The ReliefBand was applied 30-60 min preoperatively
      and left in place for 24 h. There was no statistically significant difference
      between the active and sham control groups in the incidence of
      intraoperative/postoperative nausea (30% versus 43%/23% versus 41%), vomiting
      (13% versus 9%/26 versus 37%), need for rescue antiemetics (23% versus 18%/34%
      versus 39%), or complete response (55% versus 57%/51% versus 34%). There was also
      no difference between the two groups in nausea scores, number of vomiting
      episodes, or patient satisfaction with postoperative nausea and vomiting
      management.

PMID- 16428566
TI  - Epidural anesthesia for elective cesarean delivery with intraoperative arterial
      occlusion balloon catheter placement.
AB  - Obstetric hemorrhage is a leading cause of maternal mortality. We describe the
      anesthetic management of elective cesarean delivery in patients at high risk for
      hemorrhage. The utility and limitations of intraarterial balloon catheter
      placement and epidural anesthesia are described.

PMID- 16428567
TI  - The effect of age on sciatic nerve block duration.
AB  - The physiologic changes that occur with advancing age and their effect on the
      duration of peripheral nerve blocks have yet to be defined. We prospectively
      studied the duration of sciatic nerve block using mepivacaine in younger and
      older patients. Eighty ASA physical status I-III patients, aged 18-35 (n = 40) or
      55-80 (n = 40) yr, having outpatient knee arthroscopy with a femoral block and a
      standardized sciatic nerve block were enrolled; 37 in each group completed the
      study. All patients received a Labat sciatic nerve block using 20 mL of 1.0%
      mepivacaine with 0.1 mEq/mL sodium bicarbonate and 1:400,000 (2.5 microg/mL)
      epinephrine and a femoral nerve block. The duration of sensory block (sensation
      of pinprick, temperature, and vibration), motor block (plantar and dorsi
      flexion), and complete sensory and motor block in the sciatic nerve distribution
      of the operative extremity were measured. The time for complete return of both
      sensory and motor function was longer in the older group, 329 +/- 47 min compared
      with 306 +/- 46 min (mean +/- sd) in the younger group (P = 0.04). The difference
      was small under the conditions of this study and would not be perceived
      clinically. Age also increased the time to return of vibratory sensation (younger
      = 292 +/- 58 min, older = 257 +/- 50 min; P = 0.007). The other measurements did
      not differ between groups. We conclude that age may affect peripheral nerve
      blocks and that more investigation is needed to determine the pharmacologic,
      physiologic, and chronologic factors behind these findings.

PMID- 16428568
TI  - What is the minimum effective volume of local anesthetic required for sciatic
      nerve blockade? A prospective, randomized comparison between a popliteal and a
      subgluteal approach.
AB  - For sciatic nerve blockade, no study has defined the optimal volume of local
      anesthetic required to block the nerve. The current, prospective, randomized
      investigation was designed to find a minimum volume of 1.5% mepivacaine required
      to block the sciatic nerve using the subgluteal and posterior popliteal
      approaches. A total of 56 patients undergoing foot surgery were randomly assigned
      to receive sciatic nerve block by means of a posterior subgluteal (group
      subgluteal, n = 28) or a posterior popliteal (group popliteal, n = 28)
      approaches. All blocks were performed with the use a nerve stimulator
      (stimulating frequency, 2 Hz, intensity 1.5-0.5 mA) and a perineural stimulating
      catheter. In all patients, plantar flexion of the foot was elicited at <0.5 mA,
      to maintain consistency among groups. The volume of local anesthetic used in each
      patient was based on the modified Dixon's up-and-down method. Complete anesthesia
      was defined as complete loss of pinprick sensation in the sciatic nerve
      distribution with concomitant inability to perform plantar or dorsal flexion of
      the foot 20 min after injection. The mean volume of local anesthetic required to
      block the sciatic nerve was 12 +/- 3 mL in the subgluteal group and 20 +/- 3 mL
      in the popliteal group (P < 0.05). The ED95 for adequate block of the sciatic
      nerve was 17 mL in the subgluteal group and 30 mL in the popliteal group. The
      authors conclude that a larger volume of local anesthetic is necessary to block
      the sciatic nerve at a more distal site (popliteal approach) as compared with a
      more proximal level (subgluteal approach).

PMID- 16428569
TI  - Thermographic temperature measurement compared with pinprick and cold sensation
      in predicting the effectiveness of regional blocks.
AB  - We designed this study to evaluate the usefulness of thermographic temperature
      measurement with an infrared camera, compared with patient response to cold and
      pinprick, as a means of assessing the success or failure of axillary blockades.
      Axillary blocks were performed on 25 patients undergoing surgery on the hand or
      forearm using a nerve stimulator technique with mepivacaine 1.5%. Pinprick and
      cold sensation were assessed on the operative site at 5-min intervals for 30 min.
      A thermographic image of the operative limb was recorded at similar time
      intervals. Thermographic images of the unblocked limb were taken before block
      placement and at 30 min. Temperature values at the operative site and unblocked
      limb were calculated from the thermographic images. Results revealed that
      thermography had higher combined values for sensitivity, specificity, and
      positive and negative predictive values than both cold and pinprick at all time
      intervals, with statistically significant differences at 15 min (thermography
      versus cold, P = 0.006; thermography versus pinprick, P = 0.026) and 30 min
      (thermography versus cold, P = 0.038; thermography versus pinprick, P = 0.040).
      For thermography as a method of block assessment, an optimal time of 15 min after
      mepivacaine local anesthetic injection gives the highest combined values for
      predicting a successful block (P = 0.004). We conclude that thermography provides
      an early and objective assessment of the success and failure of axillary regional
      blockades.

PMID- 16428570
TI  - Does dexamethasone improve the quality of intravenous regional anesthesia and
      analgesia? A randomized, controlled clinical study.
AB  - We investigated the anesthetic and analgesic effectiveness of adding
      dexamethasone to lidocaine for IV regional anesthesia (IVRA). Seventy-five
      patients undergoing ambulatory hand surgery were randomly assigned to one of
      three groups: group L received 3 mg/kg lidocaine, group LD received 3 mg/kg
      lidocaine + 8 mg dexamethasone, and group LDc received 3 mg/kg lidocaine for IVRA
      and 8 mg dexamethasone IV to the nonsurgical arm. IVRA was established using 40
      mL of a solution. Visual analog scale and verbal pain scores were recorded
      intraoperatively and for 2 h postoperatively. Postoperative pain was treated with
      oral acetaminophen 500 mg every 4 h when visual analog scale score was more than
      3. Time to request for the first analgesic and the total dose in the first 24 h
      were noted. Times to onset of complete sensory and motor block were similar in
      the 3 groups. The times to recovery of motor block (L = 8 [5.91-10.08] min, LD =
      13 [6.76-20.19] min, LDc = 6 [4.44-8.43] min) and sensory block (L = 7 [5.21
      10.30] min, LD = 12 [6.11-19.40] min and LDc = 6 [4.2-8.11] min) were longer in
      group LD (P < 0.05). Patients in group LD reported significantly lower pain
      scores and required less acetaminophen in the first 24 h after surgery. In
      conclusion, the addition of 8 mg dexamethasone to lidocaine for IVRA in patients
      undergoing hand surgery improves postoperative analgesia during the first
      postoperative day.

PMID- 16428571
TI  - The feasibility and efficacy of short axillary catheters for emergency upper limb
      surgery: a descriptive series of 120 cases.
AB  - We prospectively evaluated the feasibility and efficacy of a simple method for
      inserting 5.1-cm brachial plexus catheters using a fascial click technique. In
      120 patients, after inserting an axillary catheter by a resident and verifying
      adequate position using a nerve stimulator, 0.7 mL/kg 1% mepivacaine was
      injected. Success of blockade (analgesia at 40 min in the 4 terminal nerves),
      analgesia efficacy, and resident autonomy were recorded. The primary success rate
      was 87%. Reinjections were performed preoperatively and perioperatively in 40%
      and 50% of patients, respectively. The resident completed the technique in 91% of
      cases. We conclude that this technique is easily performed by residents in
      training and is associated with frequent success for anesthesia and postoperative
      analgesia.

PMID- 16428572
TI  - The impact of postoperative nasal packing on sleep-disordered breathing and
      nocturnal oxygen saturation in patients with obstructive sleep apnea syndrome.
AB  - Nasal septum surgery is frequently performed to establish a functional nasal
      airway. In these patients obstructive sleep apnea syndrome (OSAS) is frequently
      present. Although patients with OSAS are at increased risk for hypoxemia, the
      impact of postoperative nasal packing (PNP) on sleep-disordered breathing and
      oxygen desaturations in patients with OSAS is unknown. We consecutively
      investigated 40 patients undergoing endonasal surgery receiving PNP. Fifteen of
      these patients had previously diagnosed OSAS (Group 2) and 25 did not (Group 1).
      In the control group, 12 healthy patients underwent elective ear or neck surgery
      without PNP. During the preoperative and postoperative nights, we continuously
      measured oronasal flow, thoracoabdominal movements, and oxygen saturation. We
      calculated the apnea-hypopnea index (AHI) and the oxygen-desaturation index
      (ODI). Compared with the preoperative values, after the operation, neither AHI
      nor ODI changed in the control group. In contrast, in Group 1, AHI (from 11 [5
      19] to 37 [22-49]) and ODI (from 4 [2-8] to 13 [6-21]) significantly increased (P
      < 0.05), whereas in Group 2, only AHI significantly increased (from 14 [10-21] to
      39 [26-50]); ODI remained similar (13 [8-27] versus 11 [4-37]). Because ODI did
      not increase in patients with OSAS and PNP who received postoperative oxygen
      overnight, postoperative intensive care monitoring might not be necessary on a
      routine basis for all patients with PNP and OSAS.

PMID- 16428573
TI  - An evaluation of the insertion and function of a new supraglottic airway device,
      the King LT, during spontaneous ventilation.
AB  - Trials of the King LT trade mark (LT, King Systems, Noblesville, IN) in
      controlled ventilation of the lungs have shown that it is an effective
      supraglottic airway device. We designed this study to evaluate the King LT
      regarding ease of insertion, position within the airway, and anatomic sealing
      properties during spontaneous ventilation in 50 ASA physical status I-III,
      Mallampati I-III, adult patients undergoing routine general anesthesia.
      Anesthesia was induced with up to 2 microg/kg fentanyl and 1.5-2 mg/kg propofol
      and maintained with 70% N2O/30%O2 and isoflurane. Insertion time, oropharyngeal
      leak pressures, fiberoptic position, and spirometry and hemodynamic data were
      recorded. Any complications were noted. Insertion was determined to be easy and a
      patent airway was achieved in all patients. First, second, and third attempt
      insertion rates were 86%, 12%, and 2%, respectively. Time to place the King LT
      trade mark was <5 s in 90% of cases. Baseline leak pressures were 31 +/- 8.8 cm
      H2O (17-50 cm H2O). Complications included laryngospasm (1) and coughing (3) on
      extubation. The incidence of sore throat at 1 h and 24 h postoperatively was 22%
      and 15%, respectively. The King LT trade mark is a simple and reliable
      supraglottic airway device for airway management during spontaneous ventilation.

PMID- 16428574
TI  - A clinical comparison of the Flexiblade and Macintosh laryngoscopes for laryngeal
      exposure in anesthetized adults.
AB  - The Flexiblade is a laryngoscope with a flexible blade. To evaluate the efficacy
      of the Flexiblade compared with the classic Macintosh laryngoscope, we performed
      a clinical study in 200 paralyzed patients undergoing elective surgery requiring
      general anesthesia and endotracheal intubation. Direct laryngoscopy was performed
      with a size 3 Macintosh laryngoscope and the Flexiblade, with and without
      activation of the lever. The laryngeal views were recorded, without manipulation,
      according to the Cormack and Lehane classification. No laryngoscopic view
      obtained by the Macintosh blade was worse than that obtained by the Flexiblade
      without the lever activated. The Macintosh blade improved 58.5% of non-Grade I
      views obtained by the Flexiblade with its lever not activated. However, when the
      Flexiblade lever was activated, 39.6% of non-Grade I views obtained by the
      Macintosh blade were improved, whereas 84.5% of non-Grade I views obtained by the
      inactivated Flexiblade were improved. Activating the Flexiblade lever never
      caused a deterioration of view. In only one case was the view better with the
      Macintosh blade than that with the activated Flexiblade. We conclude that the
      Flexiblade, after lever activation, is significantly better than the Macintosh
      laryngoscope for laryngeal visualization in paralyzed adults (P < 0.0001).

PMID- 16428575
TI  - A comparison between the PLA Cobra and the Laryngeal Mask Airway Unique during
      spontaneous ventilation: a randomized prospective study.
AB  - The Laryngeal Mask (LMA) Unique and the Cobra Perilaryngeal Airway (PLA) are
      single-use supraglottic devices. There are no published studies comparing these
      devices during spontaneous ventilation. We compared the LMA Unique and the Cobra
      PLA with respect to 1) ventilatory variables during spontaneous ventilation, 2)
      time to achieve an effective airway, 3) airway intervention requirements, 4) cuff
      seal pressures, 5) fiberoptic score, and 6) perioperative adverse events. Eighty
      adult ASA physical status I-II patients undergoing general anesthesia for minor
      routine surgery were randomly allocated to LMA Unique or PLA Cobra for airway
      management. No statistically significant differences were found between the
      devices with respect to inspiratory tidal volume, expiratory tidal volume, end
      tidal CO2 concentration, respiratory rate, number and type of airway
      interventions required with placement, the fiberoptic score, and the incidence of
      perioperative adverse events. The oropharyngeal leak (seal) pressure was higher
      for the CobraPLA (27 +/- 7 versus 21 +/- 4 cm H2O; P < 0.001). The oxygen
      saturation was higher (98.1% +/- 1% versus 97.3% +/- 2%; P = 0.02) in the LMA
      group. Time of insertion was shorter for LMA (23.7 +/- 2 s versus 26.6 +/- 7 s; P
      = 0.02) and insertion difficulty was less for LMA (P = 0.03). As these
      differences were not judged to be clinically important, both devices appear to be
      effective in establishing an adequate airway in patients who are spontaneously
      breathing under general anesthesia.

PMID- 16428576
TI  - Laparoscopic approach to pheochromocytoma: is a lower intraabdominal pressure
      helpful?
AB  - Laparoscopic adrenalectomy is gaining popularity because of its well-documented
      benefits. The aim of our study was to see if a decreased intraoperative
      intraabdominal pressure during laparoscopic adrenalectomy would affect the
      hemodynamic variables and the serum levels of catecholamines. We randomly divided
      9 patients into 2 groups, maintaining either an intraabdominal pressure of 15 mm
      Hg (group A) or 8-10 mm Hg (group B). Norepinephrine and epinephrine blood levels
      were measured preoperatively, during endotracheal intubation, carboperitoneum,
      surgical manipulation of tumor just before the ligation of the adrenal vein, and
      tracheal extubation; the hemodynamic variables were recorded. The introduction of
      carboperitoneum resulted in an increase in heart rate and mean arterial blood
      pressure (MAP), although it was statistically insignificant. The norepinephrine
      levels showed a statistically significant increase in group A as compared with
      group B (P = 0.0002). Surgical manipulation of the tumor resulted in a
      significant increase in MAP and norepinephrine levels in group A (P = 0.007 and P
      = 0.0001, respectively). The epinephrine levels did not change as much because
      the tumor was probably predominantly norepinephrine-secreting. Norepinephrine
      levels continued to be high even during tracheal extubation in group A patients
      (P = 0.027). We conclude that a low intraabdominal pressure of 8-10 mm Hg causes
      less catecholamine release and fewer hemodynamic fluctuations.

PMID- 16428577
TI  - Acute appendicitis in a patient with undiagnosed pheochromocytoma.
AB  - Pheochromocytoma is a rare catecholamine-producing tumor that can cause severe
      hypertension and other systemic disturbances. A clinical challenge arises when a
      patient with a previously undiagnosed and untreated pheochromocytoma presents
      with a surgical emergency. We describe a patient presenting with acute
      appendicitis in whom surgery was cancelled because of suspected pheochromocytoma.
      The possibility of mortality associated with surgery in a patient with an
      undiagnosed pheochromocytoma outweighed the risk of nonoperative management for
      appendicitis. This case resulted in a nonoperative resolution of appendicitis and
      an unremarkable recovery once appropriate hypertension treatment was
      administered.

PMID- 16428578
TI  - Subarachnoid hemorrhage after lumbar puncture in a patient receiving aspirin and
      clopidrogel.

PMID- 16428579
TI  - Hasty C-arm positioning: a recipe for disaster.

PMID- 16428580
TI  - Validation of institutional support survey for anesthesiology training programs
      in the United States.

PMID- 16428581
TI  - Safety of cox-2 selective nonsteroidal antiinflammatory drugs for postsurgical
      pain.

PMID- 16428582
TI  - Routine inhaled induction in adults: a safe practice?

PMID- 16428583
TI  - Reliability measurement with unreliable method.

PMID- 16428584
TI  - Extravasation injury caused by propofol.

PMID- 16428585
TI  - Double Arndt bronchial blocker technique: was it necessary?

PMID- 16428586
TI  - Not all reasons for difficult peripheral nerve blocks are at the proximal end of
      the needle.

PMID- 16428587
TI  - Was the postoperative nerve injury really related to the performance of the
      block?

PMID- 16428588
TI  - Small group teaching and the outcomes project.

PMID- 16428589
TI  - Appropriate response to hypotension.

PMID- 16428590
TI  - Differentiating "volumetric preload monitoring" and assessing "fluid
      responsiveness".

PMID- 16428591
TI  - Is the interscalene brachial plexus block the best approach?

PMID- 16428592
TI  - Ghost-boostering phantom gradients.

PMID- 16428593
TI  - Is TNS really no big deal?

PMID- 16428594
TI  - A strange place to find a cable tie.

PMID- 16428595
TI  - Intraoperative Harlequin syndrome.

PMID- 16428596
TI  - Identification and characterization of the Arabidopsis orthologs of nuclear
      transport factor 2, the nuclear import factor of ran.
AB  - Ran is a multifunctional small GTPase that is involved in nucleocytoplasmic
      transport, mitotic spindle assembly, and nuclear envelope formation. Nuclear
      import of Ran relies on a small RanGDP-binding protein, Nuclear Transport Factor
      2 (NTF2). Three proteins are expressed in Arabidopsis (Arabidopsis thaliana) that
      show significant sequence similarity to human and yeast (Saccharomyces
      cerevisiae) NTF2. Here, we demonstrate that two of them, AtNTF2a and AtNTF2b, can
      functionally replace the essential NTF2 gene in yeast. Consistent with this
      finding, both AtNTF2a and AtNTF2b interact with yeast and Arabidopsis Ran. The
      third NTF2-related protein, AtNTL, does not functionally replace NTF2 in yeast.
      Similar to yeast NTF2-green fluorescent protein (GFP), AtNTF2a-GFP and AtNTF2b
      GFP accumulate at the nuclear rim. The AtNTF2a E38K and E91K mutants, which fail
      to bind Ran, are not functional in yeast, indicating conservation of the
      requirement for these key amino acids in plants and yeast. AtNTF2a
      overexpression, but not AtNTF2aE38K overexpression, blocks nuclear import of a
      plant transcription factor in Nicotiana benthamiana leaves, indicating that
      excess AtNTF2a disrupts nuclear import in a Ran-binding-dependent manner. On the
      basis of these results, we propose that AtNTF2a and AtNTF2b function in Ran
      import in Arabidopsis and that nuclear import of Ran is functionally conserved in
      plants.

PMID- 16428597
TI  - Forward genetic analysis of the circadian clock separates the multiple functions
      of ZEITLUPE.
AB  - The circadian system of Arabidopsis (Arabidopsis thaliana) includes feedback
      loops of gene regulation that generate 24-h oscillations. Components of these
      loops remain to be identified; none of the known components is completely
      understood, including ZEITLUPE (ZTL), a gene implicated in regulated protein
      degradation. ztl mutations affect both circadian and developmental responses to
      red light, possibly through ZTL interaction with PHYTOCHROME B (PHYB). We
      conducted a large-scale genetic screen that identified additional clock-affecting
      loci. Other mutants recovered include 11 new ztl alleles encompassing mutations
      in each of the ZTL protein domains. Each mutation lengthened the circadian
      period, even in dark-grown seedlings entrained to temperature cycles. A mutation
      of the LIGHT, OXYGEN, VOLTAGE (LOV)/Period-ARNT-Sim (PAS) domain was unique in
      retaining wild-type responses to red light both for the circadian period and for
      control of hypocotyl elongation. This uncoupling of ztl phenotypes indicates that
      interactions of ZTL protein with multiple factors must be disrupted to generate
      the full ztl mutant phenotype. Protein interaction assays showed that the ztl
      mutant phenotypes were not fully explained by impaired interactions with
      previously described partner proteins Arabidopsis S-phase kinase-related protein
      1, TIMING OF CAB EXPRESSION 1, and PHYB. Interaction with PHYB was unaffected by
      mutation of any ZTL domain. Mutation of the kelch repeat domain affected protein
      binding at both the LOV/PAS and the F-box domains, indicating that interaction
      among ZTL domains leads to the strong phenotypes of kelch mutations. Forward
      genetics continues to provide insight regarding both known and newly discovered
      components of the circadian system, although current approaches have saturated
      mutations at some loci.

PMID- 16428598
TI  - Extracellular ATP induces the accumulation of superoxide via NADPH oxidases in
      Arabidopsis.
AB  - Extracellular ATP can serve as a signaling agent in animal cells, and, as
      suggested by recent reports, may also do so in plant cells. In animal cells it
      induces the production of reactive oxygen species through the mediation of NADPH
      oxidase. Similarly, here we report that in leaves of Arabidopsis (Arabidopsis
      thaliana), applied ATP, but not AMP or phosphate, induces the accumulation of
      superoxide (O2-) in a biphasic, dose-dependent manner, with a threshold at 500 nm
      ATP. This effect did not require ATP hydrolysis for it was mimicked by ATPgammaS.
      ATP also induced increased levels of Arabidopsis respiratory burst oxidase
      homolog D (AtrbohD) mRNA, but ATP-treated plants that had disrupted AtrbohD and
      AtrbohF genes did not accumulate O2-, indicating that NADPH oxidases are
      responsible for the induced O2- accumulation. Inhibitors of mammalian P2-type ATP
      receptors abolished ATP-induced O2- production, suggesting that the ATP effects
      may be mediated through P2-like receptors in plants. Cytosolic Ca2+ and
      calmodulin are likely to help transduce the ATP responses, as they do in animal
      cells, because a Ca2+ channel blocker, a Ca2+ chelator, and calmodulin antagonist
      all reduced ATP-induced O2- accumulation. Furthermore, ATP treatment enhanced the
      expression of genes that are induced by wounds and other stresses. The ATP
      measured at wound sites averaged 40 microm, well above the level needed to induce
      O2- accumulation and gene expression changes. Transgenic plants overexpressing an
      apyrase gene had reduced O2- production in response to applied ATP and wounding.
      Together, these data suggest a possible role for extracellular ATP as a signal
      potentially in wound and stress responses.

PMID- 16428599
TI  - Control of floral meristem determinacy in petunia by MADS-box transcription
      factors.
AB  - The shoot apical meristem (SAM), a small group of undifferentiated dividing
      cells, is responsible for the continuous growth of plants. Several genes have
      been identified that control the development and maintenance of the SAM. Among
      these, WUSCHEL (WUS) from Arabidopsis (Arabidopsis thaliana) is thought to be
      required for maintenance of a stem cell pool in the SAM. The MADS-box gene
      AGAMOUS, in combination with an unknown factor, has been proposed as a possible
      negative regulator of WUS, leading to the termination of meristematic activity
      within the floral meristem. Transgenic petunia (Petunia hybrida) plants were
      produced in which the E-type and D-type MADS-box genes FLORAL BINDING PROTEIN2
      (FBP2) and FBP11, respectively, are simultaneously overexpressed. These plants
      show an early arrest in development at the cotyledon stage. Molecular analysis of
      these transgenic plants revealed a possible combined action of FBP2 and FBP11 in
      repressing the petunia WUS homolog, TERMINATOR. Furthermore, the ectopic up
      regulation of the C-type and D-type homeotic genes FBP6 and FBP7, respectively,
      suggests that they may also participate in a complex, which causes the
      determinacy in transgenic plants. These data support the model that a
      transcription factor complex consisting of C-, D-, and E-type MADS-box proteins
      controls the stem cell population in the floral meristem.

PMID- 16428600
TI  - The Arabidopsis zinc finger-homeodomain genes encode proteins with unique
      biochemical properties that are coordinately expressed during floral development.
AB  - Arabidopsis (Arabidopsis thaliana) contains approximately 100 homeobox genes,
      many of which have been shown to play critical roles in various developmental
      processes. Here we characterize the zinc finger-homeodomain (ZF-HD) subfamily of
      homeobox genes, consisting of 14 members in Arabidopsis. We demonstrate that the
      HDs of the ZF-HD proteins share some similarities with other known HDs in
      Arabidopsis, but they contain distinct features that cluster them as a unique
      class of plant HD-containing proteins. We have carried out mutational analyses to
      show that the noncanonical residues present in the HDs of this family of proteins
      are important for function. Yeast (Saccharomyces cerevisiae) two-hybrid matrix
      analyses of the ZF-HD proteins reveal that these proteins both homo- and
      heterodimerize, which may contribute to greater selectivity in DNA binding. These
      assays also show that most of these proteins do not contain an intrinsic
      activation domain, suggesting that interactions with other factors are required
      for transcriptional activation. We also show that the family members are all
      expressed predominantly or exclusively in floral tissue, indicating a likely
      regulatory role during floral development. Furthermore, we have identified loss
      of-function mutations for six of these genes that individually show no obvious
      phenotype, supporting the idea that the encoded proteins have common roles in
      floral development. Based on these results, we propose the ZF-HD gene family
      encodes a group of transcriptional regulators with unique biochemical activities
      that play overlapping regulatory roles in Arabidopsis floral development.

PMID- 16428601
TI  - Chloroplastic NAD(P)H dehydrogenase in tobacco leaves functions in alleviation of
      oxidative damage caused by temperature stress.
AB  - In this study, the function of the NAD(P)H dehydrogenase (NDH)-dependent pathway
      in suppressing the accumulation of reactive oxygen species in chloroplasts was
      investigated. Hydrogen peroxide accumulated in the leaves of tobacco (Nicotiana
      tabacum) defective in ndhC-ndhK-ndhJ (DeltandhCKJ) at 42 degrees C and 4 degrees
      C, and in that of wild-type leaves at 4 degrees C. The maximum quantum efficiency
      of PSII decreased to a similar extent in both strains at 42 degrees C, while it
      decreased more evidently in DeltandhCKJ at 4 degrees C. The parameters linked to
      CO(2) assimilation, such as the photochemical efficiency of PSII, the decrease of
      nonphotochemical quenching following the initial rise, and the photosynthetic
      O(2) evolution, were inhibited more significantly in DeltandhCKJ than in wild
      type at 42 degrees C and were seriously inhibited in both strains at 4 degrees C.
      While cyclic electron flow around PSI mediated by NDH was remarkably enhanced at
      42 degrees C and suppressed at 4 degrees C. The proton gradient across the
      thylakoid membranes and light-dependent ATP synthesis were higher in wild type
      than in DeltandhCKJ at either 25 degrees C or 42 degrees C, but were barely
      formed at 4 degrees C. Based on these results, we suggest that cyclic
      photophosphorylation via the NDH pathway might play an important role in
      regulation of CO(2) assimilation under heat-stressed condition but is less
      important under chilling-stressed condition, thus optimizing the photosynthetic
      electron transport and reducing the generation of reactive oxygen species.

PMID- 16428602
TI  - Multiple heme oxygenase family members contribute to the biosynthesis of the
      phytochrome chromophore in Arabidopsis.
AB  - The oxidative cleavage of heme by heme oxygenases (HOs) to form biliverdin
      IXalpha (BV) is the committed step in the biosynthesis of the phytochrome (phy)
      chromophore and thus essential for proper photomorphogenesis in plants.
      Arabidopsis (Arabidopsis thaliana) contains four possible HO genes (HY1, HO2-4).
      Genetic analysis of the HY1 locus showed previously that it is the major source
      of BV with hy1 mutant plants displaying long hypocotyls and decreased chlorophyll
      accumulation consistent with a substantial deficiency in photochemically active
      phys. More recent analysis of HO2 suggested that it also plays a role in phy
      assembly and photomorphogenesis but the ho2 mutant phenotype is more subtle than
      that of hy1 mutants. Here, we define the functions of HO3 and HO4 in Arabidopsis.
      Like HY1, the HO3 and HO4 proteins have the capacity to synthesize BV from heme.
      Through a phenotypic analysis of T-DNA insertion mutants affecting HO3 and HO4 in
      combination with mutants affecting HY1 or HO2, we demonstrate that both of the
      encoded proteins also have roles in photomorphogenesis, especially in the absence
      of HY1. Disruption of HO3 and HO4 in the hy1 background further desensitizes
      seedlings to red and far-red light and accelerates flowering time, with the
      triple mutant strongly resembling seedlings deficient in the synthesis of
      multiple phy apoproteins. The hy1/ho3/ho4 mutant can be rescued phenotypically
      and for the accumulation of holo-phy by feeding seedlings BV. Taken together, we
      conclude that multiple members of the Arabidopsis HO family are important for
      synthesizing the bilin chromophore used to assemble photochemically active phys.

PMID- 16428603
TI  - The interaction between DCL1 and HYL1 is important for efficient and precise
      processing of pri-miRNA in plant microRNA biogenesis.
AB  - It has been reported that some double-stranded RNA (dsRNA) binding proteins
      interact with small RNA biogenesis-related RNase III enzymes. However, their
      biological significance is poorly understood. Here we examine the relationship
      between the Arabidopsis microRNA- (miRNA) producing enzyme DCL1 and the dsRNA
      binding protein HYL1. In the hyl1-2 mutant, the processing steps of miR163
      biogenesis were partially impaired; increased accumulation of pri-miR163 and
      reduced accumulation of short pre-miR163 and mature miR163 as well as misplaced
      cleavages in the stem structure of pri-miR163 were detected. These misplaced
      cleavages were similar to those previously observed in the dcl1-9 mutant, in
      which the second double-stranded RNA binding domain of the protein was disrupted.
      An immunoprecipitation assay using Agrobacterium-mediated transient expression in
      Nicotiana benthamiana showed that HYL1 was able to form a complex with wild-type
      DCL1 protein, but not with the dcl1-9 mutant protein. We also examined miR164b
      and miR166a biogenesis in hyl1-2 and dcl1-9. Increased accumulation of pri-miRNAs
      and reduced accumulation of pre-miRNAs and mature miRNAs were detected. Misplaced
      cleavage on pri-miR164b was observed only in dcl1-9 but not in hyl1-2, whereas
      not on pri-miR166a in either mutant. These results indicate that HYL1 has a
      function in assisting efficient and precise cleavage of pri-miRNA through
      interaction with DCL1.

PMID- 16428604
TI  - Structure of a self-splicing group II intron catalytic effector domain 5:
      parallels with spliceosomal U6 RNA.
AB  - Domain 5 (D5) is absolutely required for all catalytic functions of group II
      introns. Here we describe the solution NMR structure, electrostatic calculations,
      and detailed magnesium ion-binding surface of D5 RNA from the Pylaiella
      littoralis large ribosomal RNA intron (D5-PL). The overall structure consists of
      a hairpin capped by a GNRA tetraloop. The stem is divided into lower and upper
      helices of 8 and 5 bp, respectively, separated by an internal bulge. The D5-PL
      internal bulge nucleotides stack into the helical junction, resulting in a
      coupling between the bulge A25 and the closing base pair (G8-C27) of the lower
      helix. Comparison of the D5-PL structure to previously reported related
      structures indicates that our structure is most similar, in the helical regions,
      to the crystal structure of D5 from yeast Ai5gamma (D5-Ai5gamma) and the NMR
      structure of the U6 snRNA stem-loop region. Our structure differs in many
      respects from both the NMR and X-ray structures of D5-Ai5gamma in the bulge
      region. Electrostatic calculations and NMR chemical shift perturbation analyses
      reveal magnesium ion-binding sites in the tetraloop, internal bulge, and the AGC
      triad in the lower stem. Our results suggest that the structure, electrostatic
      environment, and the magnesium ion-binding sites within the tetraloop, bulge, and
      triad regions are conserved features of the splicing machinery of both the group
      II introns and the spliceosome that are likely key for catalytic function.

PMID- 16428605
TI  - Rrp5p, a trans-acting factor in yeast ribosome biogenesis, is an RNA-binding
      protein with a pronounced preference for U-rich sequences.
AB  - Rrp5p is a trans-acting factor important for biogenesis of both the 40S and 60S
      subunit of the Saccharomyces cerevisiae ribosome. The protein contains 12
      tandemly repeated S1 RNA binding motifs in its N-terminal region, suggesting the
      ability to interact directly with the pre-rRNA. In vitro binding studies, using
      immunopurified Rrp5p and in vitro transcribed, 32P-UTP-labeled RNA fragments,
      revealed that Rrp5p is a general RNA-binding protein with a strong preference for
      single-stranded sequences rich in uridines. Co-immunoprecipitation studies in
      yeast cells expressing ProtA-tagged Rrp5p showed that the protein is still
      associated with pre-ribosomal particles containing 27SA2 pre-rRNA but not with
      particles containing the 27SB precursor. Thus, Rrp5p appears to dissociate from
      the 66S pre-ribosome upon or immediately after further processing of 27SA2 pre
      rRNA, suggesting the presence of (an) important binding site(s) within the 3'
      terminal portion of ITS1. The location of these possible binding site(s) was
      further delimited using rrp2-1 mutant cells, which accumulate the 5'-extended
      5.8S pre-rRNA species. The results indicate that association of Rrp5p with the
      pre-ribosome is abolished upon removal of a 30-nt region downstream from site A2,
      which contains two short, single-stranded U stretches. Sequence comparison shows
      that only the most 5' of these two U-rich stretches is conserved among yeast
      species whose ITS1 can functionally replace the S. cerevisiae spacer. The
      implications for the role of Rrp5p in yeast ribosome biogenesis are discussed.

PMID- 16428606
TI  - The bunyavirus nucleocapsid protein is an RNA chaperone: possible roles in viral
      RNA panhandle formation and genome replication.
AB  - Cellular RNA chaperones are crucial for the genesis of correctly folded
      functional RNAs. Using several complementary in vitro assays we find that the
      bunyavirus nucleocapsid protein (N) is an RNA chaperone. In the Bunyaviridae
      genomic RNA is in stable "panhandle" formation that arises through the hydrogen
      bonding of the terminal nucleotides of the RNA. The RNA chaperone function of N
      facilitates panhandle formation even though the termini are separated by >2 kb.
      RNA panhandle formation is likely driven by the exceptionally high base-pairing
      specificity of the terminal nucleotides as evidenced by P-num analysis. N protein
      can nonspecifically dissociate RNA duplexes. In addition, following panhandle
      formation, the RNA chaperone activity of N also appears to be involved in
      dissociation of the RNA panhandle and remains in association with the 5' terminus
      of the viral RNA following dissociation. Thus, N likely functions in the
      initiation of genome replication to allow efficient initiation of RNA synthesis
      by the viral polymerase. The RNA chaperone activity of N may be facilitated by an
      intrinsically disordered domain that catalyzes RNA unfolding driven by reciprocal
      entropy transfer. These observations highlight the essential features that are
      probably common to all RNA chaperones in which the role of the chaperone is to
      nonspecifically dissociate higher order structure and formation of functional
      higher order structure may often be predicted by RNA P-num value. The data also
      highlight features of N that are probably specifically important during
      replication of bunyavirus RNA.

PMID- 16428607
TI  - Distinct contributions of KH domains to substrate binding affinity of Drosophila
      P-element somatic inhibitor protein.
AB  - Drosophila P-element somatic inhibitor protein (PSI) regulates splicing of the P
      element transposase pre-mRNA by binding a pseudo-splice site upstream of the
      authentic splice site using four tandem KH-type RNA binding motifs. While the
      binding domains and specificity of PSI have been established, little is known
      about the contributions of each PSI KH domain to overall protein stability and
      RNA binding affinity. Using a construct containing only the RNA binding domain of
      PSI (PSI-KH03), we introduced a physiologically relevant point mutation into each
      KH domain of PSI individually and measured stability and RNA binding affinity of
      the resulting mutant proteins. Although secondary structure, as measured by
      circular dichroism spectroscopy, is only subtly changed for each mutant protein
      relative to wild type, RNA binding affinity is reduced in each case. Mutations in
      the second or third KH domains of the protein are significantly more deleterious
      to substrate recognition than mutation of the outer (first and fourth) domains.
      These results show that despite the ability of a single KH domain to bind RNA in
      some systems, PSI requires multiple tandem KH domains for specific and high
      affinity recognition of substrate RNA.

PMID- 16428609
TI  - Invited review: spray-dried dairy and dairy-like emulsions--compositional
      considerations.
AB  - Milk constituents [caseins, whey proteins (WP), lactose, and anhydrous milk fat]
      are used widely in the manufacture of dehydrated dairy and dairy-like emulsions.
      When sodium caseinate- (NaCas) and WP-stabilized emulsions with an oil-to-protein
      ratio ranging from 0.25 to 5 are dehydrated, NaCas is a more effective
      encapsulant than WP because of its superior emulsifying properties and resistance
      to heat denaturation. Denaturation degree of WP during drying has been associated
      with increased powder surface fat and larger droplet size after reconstitution.
      Encapsulation of NaCas-stabilized emulsions improves in the presence of lactose;
      powder surface fat was reduced from 30 to <5% when lactose was added at a 1:1
      ratio to NaCas in an emulsion containing 30% (wt/wt) oil. This has been related
      to the ability of lactose to form solid-like (or glassy) capsules during sudden
      dehydration. Encapsulation of WP-stabilized emulsions is not improved by addition
      of lactose, although there are conflicting reports in the literature. Storage
      stability of dehydrated dairy-like emulsions is strongly linked to lactose
      crystallization as release of encapsulated material occurs during storage at high
      relative humidities (e.g., 75%). The use of alternative carbohydrates as "matrix
      forming" materials (such as maltodextrins or gum arabic) improves storage
      stability but compromises the emulsion droplet size after reconstitution. The
      composition of the powder surface has been recognized as a key parameter in
      dehydrated emulsion quality. It is the chemical composition of the powder surface
      that dictates the behavior of the bulk in terms of wettability, flowability, and
      stability. Analyses, using electron spectroscopy for chemical analysis of the
      surface of industrial milk powders and dehydrated emulsions that mimicked the
      composition of milk, showed that powder surface is covered mainly by fat, even
      when the fat content is very low (18 and 99% surface fat coverage for skim milk
      and whole milk powders, respectively). The functional properties of milk
      constituents during emulsion dehydration are far from being thoroughly
      understood; future research needs include a) the encapsulation properties of pure
      micellar casein; b) a deeper understanding of colloidal phenomena (such as
      changes in the oil-water and air-oil interfaces) that occur before, during, and
      after dehydration, which ultimately define emulsion stability after drying; and
      c) reconciliation of the current different views on powder surface composition.

PMID- 16428608
TI  - Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing
      factor Prp8p.
AB  - The U1, U2, U4/U6, and U5 small nuclear ribonucleoproteins (snRNPs) are
      components of the spliceosome, which catalyzes pre-mRNA splicing. One of the
      largest and the most highly conserved proteins in the spliceosome is Prp8p, a
      component of the U5 snRNP. Despite its size and conservation, very few motifs
      have been identified that suggest specific biochemical functions. A variant of
      the Jab1/MPN domain found in a class of deubiquitinating enzymes is present near
      the C terminus of Prp8p. Ubiquitination regulates a broad range of cellular
      pathways, and its functions generally require ubiquitin recognition by one or
      more ubiquitin-binding domains (UBDs). No precise role for ubiquitin has been
      defined in the pre-mRNA splicing pathway, and no known UBDs have been found
      within splicing proteins. Here we show that a Prp8p fragment containing the
      Jab1/MPN domain binds directly to ubiquitin with an affinity comparable to other
      known UBDs. Several mutations within this domain that compromise splicing also
      reduce interaction of the fragment with ubiquitin-Sepharose. Our results define a
      new UBD and suggest functional links between ubiquitin and the pre-mRNA splicing
      machinery.

PMID- 16428610
TI  - The effects of dairy processes and storage on insulin-like growth factor-I (IGF
      I) content in milk and in model IGF-I-fortified dairy products.
AB  - The effects of several dairy processes on insulin-like growth factor-I (IGF-I)
      concentrations in milk and the storage stability of IGF-I-fortified dairy
      products were examined. The IGF-I content in raw milk determined by
      radioimmunoassay was significantly changed by the strength of heat treatments. In
      commercial manufacture of whole milk dry powder, IGF-I concentration was not
      significantly changed. A significant reduction in IGF-I content was found as the
      result of fermentation with a commercial starter culture. The IGF-I content in
      fortified milk and dried milk powder exhibited no significant changes over the
      tested storage periods (12 d for milk, 4 wk for dried milk powder), but the IGF-I
      content in the yogurt decreased significantly during storage. The use of IGF-I
      was varied by lactic strains and was apparent in the viable cells. When IGF-I was
      encapsulated using the surface-reforming process, the remaining IGF-I content
      after fermentation was significantly higher compared with that of the untreated
      control. Therefore, enteric coating of IGF-I before fermentation might be an
      effective method for the prevention of IGF-I degradation during fermentation.

PMID- 16428611
TI  - Preparation of liposomes from milk fat globule membrane phospholipids using a
      microfluidizer.
AB  - The isolation of milk fat globule membrane (MFGM) material from buttermilk on a
      commercial scale has provided a new ingredient rich in phospholipids and
      sphingolipids. An MFGM-derived phospholipid fraction was used to produce
      liposomes via a high-pressure homogenizer (Microfluidizer). This technique does
      not require the use of solvents or detergents, and is suitable for use in the
      food industry. The liposome dispersion had an average hydrodynamic diameter of 95
      nm, with a broad particle-size distribution. Increasing the number of passes
      through the Microfluidizer, increasing the pressure, or reducing the phospholipid
      concentration all resulted in a smaller average liposome diameter. Changing these
      variables did not have a significant effect on the polydispersity of the
      dispersion. Electron microscopy showed that the dispersions formed had a range of
      structures, including unilamellar, multilamellar, and multivesicular liposomes.
      The composition of the MFGM phospholipid material is different from that of the
      phospholipids usually used for liposome production in the pharmaceutical and
      cosmetic industries. The MFGM-derived fraction comprises approximately 25%
      sphingomyelin, and the fatty acids are primarily saturated and monounsaturated.
      These differences are likely to affect the properties of the liposomes produced
      from the phospholipid material, and it may be possible to exploit the unique
      composition of the MFGM phospholipid fraction in the delivery of bioactive
      ingredients in functional foods.

PMID- 16428612
TI  - Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on
      Cheddar cheese quality: manufacture and composition.
AB  - Eight Cheddar cheeses with 2 levels of calcium (Ca) and phosphorus (P), residual
      lactose, and salt-to-moisture ratio (S/M) were manufactured. All cheeses were
      made using a stirred-curd procedure and were replicated 3 times. Treatments with
      a high level of Ca and P were produced by setting the milk and drawing the whey
      at a higher pH (6.6 and 6.3, respectively) compared with the treatments with a
      low level of Ca and P (pH of 6.2 and 5.7, respectively). The lactose content in
      the cheeses was varied by adding lactose (2.5% by weight of milk) to the milk for
      high lactose cheeses, and washing the curd for low lactose cheeses. The
      difference in S/M was obtained by dividing the curds into halves, weighing each
      half, and salting at 3.5 and 2.25% of the weight of the curd for high and low
      S/M, respectively. All cheeses were salted at a pH of 5.4. Modifications in
      cheese-making protocols produced cheeses with desired differences in Ca and P,
      residual lactose, and S/M. Average Ca and P in the high Ca and P cheeses was 0.68
      and 0.48%, respectively, vs. 0.53 and 0.41% for the low Ca and P cheeses. Average
      lactose content of the high lactose treatments at d 1 was 1.48% compared with
      0.30% for the low lactose treatments. The S/M for the high and low S/M cheeses
      was 6.68 and 4.77%, respectively. Mean moisture, fat, and protein content of the
      cheeses ranged from 32.07 to 37.57%, 33.32 to 35.93%, and 24.46 to 26.40%,
      respectively. The moisture content differed among the treatments, whereas fat and
      protein content on dry basis was similar.

PMID- 16428613
TI  - Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on
      Cheddar cheese quality: changes in residual sugars and water-soluble organic
      acids during ripening.
AB  - Cheddar cheese ripening involves the conversion of lactose to glucose and
      galactose or galactose-6-phosphate by starter and nonstarter lactic acid
      bacteria. Under ideal conditions (i.e., where bacteria grow under no stress of
      pH, water activity, and salt), these sugars are mainly converted to lactic acid.
      However, during ripening of cheese, survival and growth of bacteria occurs under
      the stressed condition of low pH, low water activity, and high salt content. This
      forces bacteria to use alternate biochemical pathways resulting in production of
      other organic acids. The objective of this study was to determine if the level
      and type of organic acids produced during ripening was influenced by calcium (Ca)
      and phosphorus (P), residual lactose, and salt-to-moisture ratio (S/M) of cheese.
      Eight cheeses with 2 levels of Ca and P (0.67 and 0.47% vs. 0.53 and 0.39%,
      respectively), lactose at pressing (2.4 vs. 0.78%), and S/M (6.4 vs. 4.8%) were
      manufactured. The cheeses were analyzed for organic acids (citric, orotic,
      pyruvic, lactic, formic, uric, acetic, propanoic, and butyric acids) and residual
      sugars (lactose, galactose) during 48 wk of ripening using an HPLC-based method.
      Different factors influenced changes in concentration of residual sugars and
      organic acids during ripening and are discussed in detail. Our results indicated
      that the largest decrease in lactose and the largest increase in lactic acid
      occurred between salting and d 1 of ripening. It was interesting to observe that
      although the lactose content in cheese was influenced by several factors (Ca and
      P, residual lactose, and S/M), the concentration of lactic acid was influenced
      only by S/M. More lactic acid was produced in low S/M treatments compared with
      high S/M treatments. Although surprising for Cheddar cheese, a substantial amount
      (0.2 to 0.4%) of galactose was observed throughout ripening in all treatments.
      Minor changes in the levels of citric, uric, butyric, and propanoic acids were
      observed during early ripening, whereas during later ripening, a substantial
      increase was observed. A gradual decrease in orotic acid and a gradual increase
      in pyruvic acid content of the cheeses were observed during 12 mo of ripening. In
      contrast, acetic acid did not show a particular trend, indicating its role as an
      intermediate in a biochemical pathway, rather than a final product.

PMID- 16428614
TI  - Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on
      Cheddar cheese quality: proteolysis during ripening.
AB  - Proteolysis in cheese is influenced by the state of proteins (protein-calcium
      phosphate interactions), level of indigenous milk enzymes (plasmin), externally
      added milk-clotting enzymes (chymosin), and endogenous and exogenous enzymes from
      starter and non-starter lactic acid bacteria (NSLAB). The objective of this study
      was to determine how different levels of calcium (Ca) and phosphorus (P),
      residual lactose, and salt-to-moisture ratio (S/M) in cheese influence
      proteolysis during ripening. Eight cheeses with 2 levels of Ca and P (0.67 and
      0.47% vs. 0.53 and 0.39%, respectively), 2 levels of lactose at pressing (2.4 vs.
      0.78%), and 2 levels of S/M (6.4 vs. 4.8%) were manufactured. The cheeses were
      analyzed for changes in pH 4.6-soluble N, and starter and NSLAB counts during 48
      wk of ripening. Cheeses at d 1 were also analyzed for residual chymosin, plasmin,
      and plasminogen activity. A significant increase in soluble N was observed during
      ripening for all the treatments. Cheeses with low Ca and P, low lactose, and low
      S/M treatments exhibited higher levels of proteolysis as compared to their
      corresponding high treatments. Differences in the rate of proteolysis for cheeses
      with different levels of Ca and P might be due to changes in protein conformation
      and differences in residual chymosin in the cheeses. Cheeses with low Ca and P
      were manufactured by lowering the pH at set and drain, which led to higher
      chymosin retention in cheeses with low Ca and P compared with high Ca and P.
      Differences in proteolysis between treatments with different levels of lactose
      were also partly attributed to residual chymosin activity. In all treatments, a
      major fraction of plasmin existed as plasminogen, indicating minimal contribution
      of plasmin to proteolysis in Cheddar cheeses. The number of starter bacteria, in
      all treatments, decreased significantly during ripening. However, the decrease
      was larger in the case of high S/M treatments compared with low S/M treatments.
      In contrast, the number of NSLAB increased during ripening, and low S/M cheeses
      had higher counts compared with high S/M cheeses. The differences in proteolysis
      due to S/M were partially attributed to changes in protein conformation or
      bacterial proteolytic activity.

PMID- 16428615
TI  - Influence of condensed sweet cream buttermilk on the manufacture, yield, and
      functionality of pizza cheese.
AB  - Compositional changes in raw and pasteurized cream and unconcentrated sweet cream
      buttermilk (SCB) obtained from a local dairy were investigated over 1 yr. Total
      phospholipid (PL) composition in SCB ranged from 0.113 to 0.153%. Whey protein
      denaturation in pasteurized cream over 1 yr ranged from 18 to 59%. Pizza cheese
      was manufactured from milk standardized with condensed SCB (approximately 34.0%
      total solids, 9.0% casein, 17.8% lactose). Effects of using condensed SCB on
      composition, yield, PL recovery, and functional properties of pizza cheese were
      investigated. Cheesemilks were prepared by adding 0, 2, 4, and 6% (wt/wt)
      condensed SCB to part-skim milk, and cream was added to obtain cheesemilks with
      approximately 11.2 to 12.7% total solids and casein:fat ratio of approximately 1.
      Use of condensed SCB resulted in a significant increase in cheese moisture.
      Cheese-making procedures were modified to obtain similar cheese moisture
      contents. Fat and nitrogen recoveries in SCB cheeses were slightly lower and
      higher, respectively, than in control cheeses. Phospholipid recovery in cheeses
      was below 40%. Values of pH and 12% trichloro-acetic acid-soluble nitrogen were
      similar among all treatments. Cheeses made from milk standardized with SCB showed
      less melt and stretch than control cheese, especially at the 4 and 6% SCB levels.
      Addition of SCB significantly lowered free oil at wk 1 but there were no
      significant differences at wk 2 and 4. Use of SCB did not result in oxidized
      flavor in unmelted cheeses. At low levels (e.g., 2% SCB), addition of condensed
      SCB improved cheese yield without affecting compositional, rheological, and
      sensory properties of cheese.

PMID- 16428616
TI  - Effect of milk protein standardization using different methods on the composition
      and yields of Cheddar cheese.
AB  - Two sets of Cheddar cheese were made in which the milk protein level (%, wt/wt)
      was increased from 3.3 (Control A, CA) to 3.6 (set A) or from 3.3 (control B, CB)
      to 4.0 (set B) by the addition of phosphocasein (PC), milk protein concentrate
      (MPC), or freshly prepared ultrafiltered milk retentate (UFR). The cheeses were
      denoted CA, PCA, MPCA, and UFRA from set A, and CB, PCB, MPCB, and UFRB, from set
      B, respectively. The level of cheese moisture decreased significantly on
      increasing milk protein level from 3.3 to 3.6 or 4.0% (wt/wt), but was not
      affected significantly by the method of protein standardization. The percentage
      milk fat recovered to cheese increased significantly on increasing the level of
      milk protein from 3.3 to 3.6% (wt/wt) with PC, and from 3.3 to 4.0% (wt/wt) with
      PC, MPC, and UFR. Increasing milk protein level from 3.3 to 4.0% (wt/wt) with PC
      significantly increased the percentage of milk protein recovered to cheese.
      Actual cheese yield increased significantly with milk protein level. The yield of
      cheese per 100 kg of milk normalized to reference levels of fat (3.4%, wt/wt) and
      casein (2.53%, wt/wt) indicated no significant effects of protein content or
      standardization treatment on yield. However, the moisture-adjusted yield per 100
      kg of milk with reference levels of fat and casein increased significantly on
      increasing the protein content from 3.3 to 3.6% (wt/wt) with MPC and from 3.3 to
      4.0% (wt/wt) with PC, MPC, and UFR.

PMID- 16428617
TI  - Molecular characterization of peptides released from beta-lactoglobulin and alpha
      lactalbumin via cardosins A and B.
AB  - Crude mixtures of aspartic proteases from flowers of the plant Cynara cardunculus
      have been studied frequently, as have activities of such enzymes (in pure form)
      on caseins from bovine, ovine, and caprine sources. This research study addressed
      pure bovine whey protein as substrates; that is, alpha-lactalbumin (alphaLA) and
      beta-lactoglobulin (alpha-LG), submitted to hydrolysis by 1 of 2 aspartic
      proteases (cardosins A and B), previously extracted and purified from C.
      cardunculus. Samples collected, following incubation at 55 degrees C and pH 5.2,
      were assayed by fast protein liquid chromatography, reversed phase-high
      performance liquid chromatography, and tricine-sodium dodecyl sulfate
      polyacrylamide gel electrophoresis; the major peptides released were then
      collected and sequenced by Edman degradation. Cardosin B and, to a lesser degree,
      cardosin A showed proteolytic activity toward alpha-LA, but the hydrolyzates
      produced were characterized by distinct peptide profiles. Cardosin B possesses a
      broad specificity, and produces several hydrophobic peptides (at least 5, with
      molecular mass in the range 2 to 8 kDa) in the early stages, which eventually
      become more hydrophilic (with molecular mass below 2 kDa) at later stages of
      hydrolysis. Cardosin A was found to cleave alpha-LA at the peptide bonds Phe28
      Arg29, Gly54-Tyr55, Ala59-Ile60, Leu71-Phe72, and Leu105-Thr106, whereas cardosin
      B cleaved Ala19-Glu20, Phe28-Arg29, Glu30-Leu31, Tyr37-Gly38, Trp45-Val46, Phe50
      His51, Ala59-Ile60, Ser66-Thr67, Leu71-Phe72, Phe72-Gln73, Gln73-Ile74, Ile78
      Trp79, Leu115-Asp116, and Leu124-Ala125. Conversely, cardosins A and B are
      apparently not active on beta-LG.

PMID- 16428618
TI  - Comparison of descriptive sensory analysis and chemical analysis for oxidative
      changes in milk.
AB  - Oxidation in 3 types of bovine milk with different fatty acid profiles obtained
      through manipulation of feed was evaluated by analytical methods quantifying the
      content of potential antioxidants, the tendency of formation of free radicals,
      and the accumulation of primary and secondary oxidation products. The milk
      samples were evaluated in parallel by descriptive sensory analysis by a trained
      panel, and the correlation between the chemical analysis and the descriptive
      sensory analysis was evaluated. The fatty acid composition of the 3 types of milk
      was found to influence the oxidative and lipolytic changes occurring in the milk
      during chill storage for 4 d. Sensory analysis and chemical analysis showed high
      correlation between the typical descriptors for oxidation such as cardboard,
      metallic taste, and boiled milk and specific chemical markers for oxidation such
      as hexanal. Notably, primary oxidation products (i.e., lipid hydroperoxides) and
      even the tendency of formation of radicals as measured by electron spin resonance
      spectroscopy were also highly correlated to the sensory descriptors for
      oxidation. Electron spin resonance spectroscopy should accordingly be further
      explored as a routine method for detection of early events in lipid oxidation in
      milk to predict shelf-life.

PMID- 16428619
TI  - Flavor profiles of full-fat and reduced-fat cheese and cheese fat made from aged
      Cheddar with the fat removed using a novel process.
AB  - Many consumers are concerned with fat intake. However, many reduced-fat foods,
      including reduced-fat cheese, lack robust flavors. The objectives of this study
      were to characterize the flavors found in full-fat cheese, cheese fat, and
      reduced-fat cheese made from aged Cheddar using a novel process to remove the fat
      (Nelson and Barbano, 2004). Two full-fat, aged cheeses (9 and 39 mo) were
      selected, and the fat was removed using the novel fat removal process. Full-fat
      cheeses, shredded and reformed full-fat cheeses, corresponding reduced-fat
      cheeses, and cheese fats were then analyzed using descriptive sensory and
      instrumental analysis followed by consumer acceptance testing. Cheeses were
      extracted with diethyl ether followed by isolation of volatile material by high
      vacuum distillation. Volatile extracts were analyzed using gas chromatography/
      olfactometry with aroma extract dilution analysis. Selected compounds were
      quantified. The 39-mo cheese was characterized by fruity and sulfur notes, and
      the 9-mo-old cheese was characterized by a spicy/brothy flavor. Reduced-fat
      cheeses had similar flavor profiles with no difference in most sensory attributes
      to corresponding full-fat cheeses. Sensory profiles of the cheese fats were
      characterized by low intensities of the prominent flavors found in the full-fat
      cheeses. Instrumental analysis revealed similar trends. Consistent with sensory
      analysis, there were lower concentrations and log(3) flavor dilution factors for
      most compounds in the cheese fats compared with both the reduced- and full-fat
      cheeses, regardless of compound polarity. Consumers found the intensity of flavor
      in the reduced-fat cheese to be equal to the full-fat cheeses. This study
      demonstrated that when fat was removed from aged full-fat Cheddar cheese, most of
      the flavor and flavor compounds remained in the cheese and were not removed with
      the fat.

PMID- 16428620
TI  - Production and processing of milk from transgenic goats expressing human lysozyme
      in the mammary gland.
AB  - The potential for applying biotechnology to benefit animal agriculture and food
      production has long been speculated. The addition of human milk components with
      intrinsic antimicrobial activity and positive charge to livestock milk by genetic
      engineering has the potential to benefit animal health, as well as food safety
      and production. We generated one line of transgenic goats as a model for the
      dairy cow designed to express human lysozyme in the mammary gland. Here we report
      the characterization of the milk from 5 transgenic females of this line
      expressing human lysozyme in their milk at 270 microg/mL or 68% of the level
      found in human milk. Milk from transgenic animals had a lower somatic cell count,
      but the overall component composition of the milk and milk production were not
      different from controls. Milk from transgenic animals had a shorter rennet
      clotting time and increased curd strength. Milk of such nature may be of benefit
      to the producer by influencing udder health and milk processing.

PMID- 16428621
TI  - Compositional and functional properties of buttermilk: a comparison between
      sweet, sour, and whey buttermilk.
AB  - Buttermilk is a dairy ingredient widely used in the food industry because of its
      emulsifying capacity and its positive impact on flavor. Commercial buttermilk is
      sweet buttermilk, a by-product from churning sweet cream into butter. However,
      other sources of buttermilk exist, including cultured and whey buttermilk
      obtained from churning of cultured cream and whey cream, respectively. The
      compositional and functional properties (protein solubility, viscosity,
      emulsifying and foaming properties) of sweet, sour, and whey buttermilk were
      determined at different pH levels and compared with those of skim milk and whey.
      Composition of sweet and cultured buttermilk was similar to skim milk, and
      composition of whey buttermilk was similar to whey, with the exception of fat
      content, which was higher in buttermilk than in skim milk or whey (6 to 20% vs.
      0.3 to 0.4%). Functional properties of whey buttermilk were independent of pH,
      whereas sweet and cultured buttermilk exhibited lower protein solubility and
      emulsifying properties as well as a higher viscosity at low pH (pH <or= 5).
      Sweet, sour, and whey buttermilks showed higher emulsifying properties and lower
      foaming capacity than milk and whey because of the presence of milk fat globule
      membrane components. Furthermore, among the various buttermilks, whey buttermilk
      was the one showing the highest emulsifying properties and the lowest foaming
      capacity. This could be due to a higher ratio of phospholipids to protein in whey
      buttermilk compared with cultured or sweet buttermilk. Whey buttermilk appears to
      be a promising and unique ingredient in the formulation of low pH foods.

PMID- 16428622
TI  - Impact of lowering dietary cation-anion difference in nonlactating dairy cows: a
      meta-analysis.
AB  - A meta-analysis of previous studies was performed to clarify the response of
      prepartum dairy cows to lowering dietary cation-anion difference (DCAD) and to
      compare different equations that have been proposed to calculate DCAD. Twenty-two
      published studies containing 75 treatment groups met criteria for inclusion in
      the meta-analysis. Five different equations used to calculate DCAD were compared
      for their association with clinical milk fever and urinary pH. The DCAD equation
      (Na + K) - (Cl + 0.6 S) was the most highly associated with clinical milk fever
      (R(2) = 0.44) and urinary pH (R(2) = 0.85). Lowering DCAD reduced clinical milk
      fever but also reduced DM intake. Lowered DCAD was associated with reduced
      urinary pH, blood bicarbonate, and blood CO(2), suggesting a metabolic acidosis
      with respiratory compensation. Blood pH was very slightly lowered by lowered
      DCAD. Lowering DCAD increased ionized Ca in blood before and at calving. The
      model predicted that lowering DCAD from +300 to 0 mEq/kg reduced risk for
      clinical milk fever from 16.4 to 3.2%, reduced urinary pH from about 8.1 to 7.0,
      and reduced DM intake by 11.3%.

PMID- 16428623
TI  - Short communication: bulk tank total bacterial count in dairy sheep: factors of
      variation and relationship with somatic cell count.
AB  - A total of 9,353 records for bulk tank total bacterial count (TBC) were obtained
      over 1 yr from 315 dairy ewe flocks belonging to the Sheep Improvement Consortium
      (CPO) in Castilla-Leon (Spain). Analysis of variance showed significant effects
      of flock, breed, month within flock, dry therapy, milking type and installation,
      and logSCC on logTBC. Flock and month within flock were important variation
      factors as they accounted for 22.0 and 22.1% of the variance, respectively.
      Considerable repeatability values were obtained for both random factors. Hand
      milking and bucket-milking machines elicited highest logTBC (5.31), whereas
      parlor systems with looped milkline (5.01) elicited the lowest logTBC. The
      implementation of dry therapy practice (5.12) showed significantly lower logTBC
      than when not used (5.25). Variability in logTBC among breeds ranged from 5.24
      (Awassi) to 5.07 (Churra). However, clinical outbreaks of contagious agalactia
      did not increase TBC significantly. A statistically significant relationship was
      found between logTBC and logSCC, the correlation coefficient between the
      variables being r = 0.23. Programs for improving milk hygiene should be
      implemented for both total bacterial count and somatic cell count variables at
      the same time.

PMID- 16428624
TI  - Identification, sequence analysis and mRNA tissue distribution of the bovine
      sterol transporters ABCG5 and ABCG8.
AB  - The family of ATP-binding cassette (ABC) transporters consists of several
      transmembrane proteins that use ATP hydrolysis as an energy source for the
      transport of a variety of substances through cellular membranes. Two members of
      this family, ABCG5 and ABCG8, are implicated in the intestinal absorption and
      biliar excretion of sterols. Cholesterol content in milk is highly variable among
      species, breeds, and individuals of the same species, but a potential application
      of these genes in lipid homeostasis in the mammary gland has never been
      addressed. In the present work, expression of ABCG5 and ABCG8 in the bovine was
      demonstrated for the first time and characterized by quantitative PCR. The entire
      coding region and promoter area were sequenced and screened for motifs involved
      in lipid homeostasis. Both ABCG5 and ABCG8 presented a high level of length and
      sequence identity with other mammalian species. In the intergenic promoter
      region, 2 GATA boxes, a liver receptor homolog-1 response element, and a nuclear
      factor-kappaB response element, important factors in other lipid regulatory
      processes, were identified. As expected, high expression levels of both ABCG5 and
      ABCG8 were present in liver and digestive tract samples, and interestingly, in
      the mammary gland, opening new avenues for further investigation about their
      potential role in lipid trafficking and excretion during lactation.

PMID- 16428625
TI  - Changes occurring in immune responsiveness of single- and twin-bearing Comisana
      ewes during the transition period.
AB  - Changes induced by twin and single lambing in the immune response of 16
      periparturient Comisana ewes were studied. Cell-mediated immune responses were
      evaluated by means of skin tests performed from 3 wk before and up to d 35 after
      parturition. At d 21 and 7 before lambing, the sheep received an intramuscular
      injection of the antigen keyhole limpet hemocyanin (KLH), to which the animals
      had not been previously exposed, to determine their humoral immune response.
      Starting 3 wk before lambing and up to d 35 postlambing, the ewes were sampled to
      determine the plasma concentrations of anti-KLH antibody (IgG), IL-6, and IL-1
      beta. From parturition through d 35 postpartum, individual milk samples were
      collected for determination of anti-KLH IgG titers and IL-6 and IL-1beta
      concentrations by means of a capture ELISA. The number of lambs born affected IL
      6 concentrations in ewe plasma; IL-6 secretion always was higher in ewes birthing
      twins than in single-lambing ewes. Apart from the number of lambs born, the
      concentrations of plasma IL-6 in ewes were higher at lambing than at d 21
      antepartum and at d 35 postpartum. An interaction of number of lambs born x time
      of sampling was observed for plasma antibody titers to KLH. The IgG
      concentrations were significantly higher in single-bearing ewes than in twin
      bearing ewes before parturition and were very similar across groups after
      parturition. A time effect was found for the cell-mediated immune response and
      for anti-KLH IgG concentrations in milk, such that at parturition, cellular
      responses were lowest, and the anti-KLH IgG concentration was highest. A
      significant correlation was found for IgG titers to KLH in plasma and milk.
      Results indicate that IL-6 concentrations in blood can be considered a reliable
      indicator of stress connected to lambing and that the mammary gland is a
      microenvironment unrelated to blood stream with respect to interleukins
      expression. In contrast, a relationship was found for the IgG secretions in milk
      and blood, which suggests that the assessment of humoral immune status may be
      combined with milking routine in dairy animals.

PMID- 16428626
TI  - Age-specific characteristics of ELISA and fecal culture for purpose-specific
      testing for paratuberculosis.
AB  - Paratuberculosis is a chronic infection, and animals are not equally affected by
      it. Therefore, diagnostic tests that are able to detect different stages of the
      infection are needed for objective decision making. A longitudinal study was
      carried out to describe the ability of 2 tests to predict 2 conditions in dairy
      cattle: "infection" and "infectious," exemplifying 2 different purposes of
      testing. "Infection" is the term of choice for certification and eradication
      purposes, and "infectious" is more relevant for control purposes. In the study
      period of 3 yr, repeated sampling of milk (n = 23,219) and feces (n = 8,832) was
      performed. A total of 1,985 Danish dairy cows provided material for the study.
      Milk samples were analyzed for antibodies using an ELISA, and fecal samples were
      analyzed for mycobacteria by culture. A reference test to correctly classify
      cattle antemortem does not exist; thus, "infection" and "infectious" were defined
      by repeated testing using one test as the condition to be detected by the other
      test. Fecal culture responses were evaluated against antibody status, and ELISA
      responses were evaluated against detected bacterial shedding. The results of this
      study indicate that the ability of both tests to detect "infection" increases
      almost linearly from 2 to 5 yr of age, whereas the ability of both tests to
      detect "infectious" is not affected by age. Purpose-specific tests are required
      to appropriately interpret and use test results for management of
      paratuberculosis, and relevant covariates, such as age, should be included when
      possible.

PMID- 16428627
TI  - Herd- and cow-level prevalence of digital dermatitis in the Netherlands and
      associated risk factors.
AB  - The objective of this cross-sectional study was to reevaluate the prevalence of
      digital dermatitis (DD) and associated risk factors in The Netherlands. Between
      May 2002 and December 2003, information about the presence or absence of DD
      lesions and other claw disorders on the hind claws of dairy cows in The
      Netherlands was collected by 20 hoof trimmers during trimming of all dairy cows
      in 383 herds. A questionnaire was used to acquire information regarding
      management and housing. Additional information, such as parity, breed, and stage
      of lactation of the cows, was provided by the Dutch Herd Book Organization.
      Digital dermatitis was present in 21.2% (SE = 0.3) of the study population (n =
      22,454 cows). The herd prevalence varied from 0% (9.1% of the herds) to 83.0%.
      Most common was herd prevalence between 5 and 10%. The Holstein-Friesian breed
      was at higher risk for DD [odds ratio (OR) = 1.7] than was the Meuse Rhine IJssel
      breed (dual purpose breed). The risk for DD decreased with increasing parity.
      Cows at the peak of their lactation (30 to 60 d in milk) and in the third parity
      had higher odds for DD in comparison with cows that were later than 60 DIM. The
      presence of other claw disorders, such as interdigital dermatitis/heel horn
      erosion (IDHE), interdigital hyperplasia (HYP), and interdigital phlegmon,
      appeared to be predisposing for DD. Based on estimation of the population
      attributable fraction, it was concluded that if IDHE, HYP, and interdigital
      phlegmon were not present among the study population, respectively, 32.2, 9.0,
      and 1.1% of the DD cases could have been prevented. The risk for DD slightly
      decreased when cows affected by IDHE had access to pasture. Because of the
      interrelation between infectious claw disorders, an effective intervention
      strategy against DD should focus on an integrated approach to the control of all
      infectious claw diseases. Cows trimmed >12 mo before the study (during regular
      trimming of the entire herd) were at lower risk for DD than were cows that were
      trimmed at shorter intervals. Animals that had >8 h of access to pasture were at
      higher risk for DD (OR = 1.6) compared with no access to pasture. Finally, cows
      in small-sized herds (<45 cows) affected with HYP were at lower risk (OR = 0.6)
      for DD than were cows affected with HYP in medium- and large-sized herds (60 to
      85 cows per herd).

PMID- 16428628
TI  - Seasonal and lactational changes in mineral composition of milk from Iberian red
      deer (Cervus elaphus hispanicus).
AB  - Milk minerals are important for calf growth, and they have other roles as well,
      such as immune regulation. This 2-yr study examined content of Ca, P, Mg, Na, K,
      Fe, and Zn in milk of 54 Iberian red deer hinds through 18 wk of lactation. Mean
      mineral composition of fresh milk was ash = 1.168 +/- 0.007%, Ca = 2,330 +/- 20
      mg/kg, P = 640 +/- 10 mg/kg, K = 1,100 +/- 10 mg/kg, Na = 385 +/- 3 mg/kg, Mg =
      138 +/- 1 mg/kg, Zn = 12.5 +/- 0.2 mg/kg, and Fe = 0.65 +/- 0.03 mg/kg. All
      minerals except Mg varied by week of lactation, but variation was usually <10%
      except for Fe (83% variation) and Zn (30% variation); both of those minerals
      increased as lactation proceeded. Increased concentrations of Fe and Zn in later
      lactation compensated for the reduction in milk production in mid and late
      lactation such that daily production was less variable for Fe (55% variation) or
      Zn (79% variation) than for other minerals (118 to 135% variation). Potassium
      content of milk decreased across time, but that effect occurred primarily during
      the last few weeks of lactation. Calving later vs. early in the calving season
      had variable effects on concentrations of different minerals: P, Mg, and K
      concentrations were not affected; Ca, Mg, and Na were all lower in milk from
      later calving hinds; and both Fe and Zn had higher concentrations in milk from
      hinds that calved later in the season. Lactating hinds seem to maintain a more
      stable daily yield of the microminerals Fe and Zn in milk compared with more
      variable concentrations of macrominerals as lactation progresses. Because of the
      essential role of Fe and Zn in immune function, a more stable supply of those
      minerals might be important to the health of growing red deer calves.

PMID- 16428629
TI  - Acute experimental mastitis is not causal toward the development of energy
      related metabolic disorders in early postpartum dairy cows.
AB  - Twenty Holstein cows in early lactation (7 d in milk) were administered 100
      microg of Escherichia coli lipopolysaccharide (LPS) dissolved in 10 mL of sterile
      0.9% NaCl saline (treatment; TRT) or 10 mL of sterile saline (control) into both
      right mammary quarters to test the hypothesis that acute experimental mastitis
      would have negative impacts on aspects of energy metabolism that might lead to
      the development of metabolic disorders. A primed continuous intravenous infusion
      (14-micromol/kg of BW priming dose; 11.5-micromol/kg of BW per h continuous
      infusion) of 6,6-dideuterated glucose was used to determine pre- and
      posttreatment glucose kinetics using steady-state tracer methodologies. The LPS
      treated cows displayed productive, clinical, and physiological signs of moderate
      to severe inflammation; control cows displayed no signs of immune activation.
      Pretreatment glucose rates of appearance (Ra) into plasma were similar (715 and
      662 +/- 33 mmol/h for TRT and control, respectively) between treatment groups.
      Intramammary LPS infusion into TRT cows resulted in increased glucose Ra relative
      to control cows (mean glucose Ra from 150 through 270 min after intramammary
      infusion were 815 and 674 +/- 21 mmol/h for TRT and control cows, respectively).
      Furthermore, plasma concentrations of glucose increased, whereas plasma
      nonesterified fatty acids, glycerol, and beta-hydroxybutyrate concentrations
      decreased, in TRT relative to control cows. Interestingly, plasma insulin
      concentration increased dramatically in TRT cows and occurred prior to the small
      increase in plasma glucose concentration. Although these results only represent
      the early stages of inflammation, they are not consistent with a causal
      relationship between mastitis and energy-related metabolic disorders and instead
      suggest a coordinated protective effect by the immune system on metabolism during
      the early stages of mammary insult.

PMID- 16428630
TI  - Partial feed restriction decreases growth hormone receptor 1A mRNA expression in
      postpartum dairy cows.
AB  - Uncoupling of the growth hormone (GH) axis in early postpartum dairy cows is
      correlated with a decrease in liver GH receptor (GHR) 1A mRNA and a decrease in
      liver GH receptor protein. Postpartum recoupling of the GH axis is also
      correlated with GHR 1A mRNA and GHR protein. We hypothesized that dry matter
      intake (DMI) partially controls the increase in GHR 1A mRNA postpartum. Prepartum
      Holstein dairy cows (n = 11) were offered feed ad libitum. After calving, 6 cows
      were fed 70% of their expected DMI (feed restriction) for 14 d and 5 cows were
      fed ad libitum (control). Both groups were fed ad libitum after d 14. Liver was
      biopsied prepartum and on d 1, 7, 14, and 21 postpartum; blood was sampled
      throughout the experimental period. Rate of increase in postpartum milk
      production was less for feed-restricted cows. The GHR 1A mRNA decreased from
      prepartum to d 1 postpartum and subsequently increased. Rate of postpartum
      increase in GHR 1A mRNA was less in feed-restricted cows. Diminished GHR 1A
      persisted for at least 7 d after feed-restricted cows returned to ad libitum
      feeding. Liver insulin-like growth factor-I mRNA concentrations decreased from
      prepartum to d 1 as well, but were similar for feed restricted and control
      thereafter. We concluded that DMI partially controls GHR 1A mRNA expression in
      early postpartum dairy cows and that the decrease in GHR 1A in response to feed
      restriction persisted for at least 1 wk after ad libitum feeding was restored.

PMID- 16428631
TI  - Time and incidence of ovulation and conception rates after incorporating
      estradiol cypionate into a timed artificial insemination protocol.
AB  - Two experiments were conducted to determine the effect of estradiol cypionate
      (ECP), when incorporated into a conventional GnRH-PGF(2alpha)-GnRH timed
      artificial insemination protocol (Ovsynch), on systemic estradiol (E(2)), time
      and incidence of ovulation, luteal development, and conception rate in Holstein
      cows. Our objective was to determine if administration of 0.25 mg of ECP at the
      time of the second GnRH injection would effectively synchronize ovulation and
      increase conception rate. In Experiment 1, lactating Holstein cows (n = 23; 58.7
      +/- 1.2 d in milk) were synchronized with PGF(2alpha) (at d -10). Ten days later,
      Ovsynch was initiated with the administration of 100 mug of GnRH (d 0) followed
      by PGF(2alpha) on d 7. On d 9, cows were assigned randomly to be treated with
      either GnRH + 0.25 mg of ECP (OVS-ECP; n = 11) or GnRH and 1 mL of cottonseed oil
      (OVS-C; n = 12). Ovarian activity was monitored by ultrasonography on d 0, 7, and
      9. To determine the time of ovulation, ultrasound examinations were conducted at
      12 and 20 h posttreatment and then at least every 3 h until either 36 h
      posttreatment or ovulation was observed. Blood samples were collected on d 0, 7,
      9, and 16 for progesterone analysis. Blood samples also were collected at the
      time of treatment (d 9, 0 h) and at 6, 12, 20, and 28 h for E(2) analysis.
      Incidence of ovulation did not differ between treatments. Mean ovulation time
      relative to the second GnRH administration was similar between treatments. Serum
      progesterone concentration did not differ between treatments at any time. Serum
      E(2) concentration was not different at the time of treatment (0 h); however,
      mean E(2) concentration was greater for the OVS-ECP group at 6 and 12 h after
      treatment compared with OVS-C. In Experiment 2, lactating dairy cows (n = 333) in
      3 commercial herds were randomly assigned to OVS-ECP (n = 169) or OVS-C (n =
      164). Cows were inseminated 22 to 24 h posttreatment. Conception rates did not
      differ between treatments. Estradiol cypionate treatment was successful in
      increasing serum E(2) when administered at the time of the second dose of GnRH in
      the Ovsynch protocol. Conception rates, however, were not affected by treatment.

PMID- 16428632
TI  - Strategies to improve the therapy of retained fetal membranes in dairy cows.
AB  - In this field trial, a protocol for the treatment of retained fetal membranes
      (RFM) without any intrauterine therapy was compared with 3 protocols based on the
      intrauterine use of antibiotic pills (AP), the manual removal (MR) of the fetal
      membranes, or the combination of both (PR). The study was conducted on 5
      commercial dairy farms in Germany. Cows with RFM for at least 24 h after calving
      were assigned to 1 of 4 treatment groups. Cows of all groups with a rectal
      temperature >or= 39.5 degrees C received a systemic antibiotic treatment with
      ceftiofur (1 mg/kg per d) for 3 to 5 consecutive days. In case of continued fever
      after 5 treatments, cows received a different antibiotic as an escape therapy. In
      the reference group (REF; n = 131), cows did not receive any additional
      treatment. All cows in group AP (n = 119) received intrauterine treatment with
      antibiotic pills consisting of 1,000 mg of ampicillin and 1,000 mg of cloxacillin
      for 3 consecutive days. In group MR (n = 121), an attempt was made to remove the
      fetal membranes manually, but uterine pills were not administered. In group PR (n
      = 130), an attempt was made to remove the fetal membranes manually and all cows
      received a local antibiotic treatment as in group AP. All cows received 2 doses
      of 25 mg of PGF(2alpha): one dose between 18 and 24 d and another between 32 and
      38 d postpartum. Statistical analyses were performed using binary logistic
      regression models and survival analyses with group REF as reference. Of all
      animals, 79.8% had a body temperature of >or= 39.5 degrees C at least once within
      10 d postpartum and were treated with ceftiofur. Occurrence of fever within 10 d
      postpartum was significantly lower in groups AP and PR compared with reference
      group REF, but was not different between groups MR and REF. Risk of receiving an
      escape therapy in case of fever after 5 treatments with ceftiofur did not differ
      among groups. Reproductive performance measures did not differ significantly
      between group REF and any of the comparison groups. Compared with a treatment
      protocol based only on systemic treatment with antibiotics for cows with a fever,
      neither intrauterine antibiotics nor manual removal of fetal membranes alone or
      in combination reduced proportions of cows needing an escape therapy nor did
      those treatments improve reproductive measures in the current lactation. Systemic
      treatment alone based on elevated rectal temperature was effective and reduced
      use of antibiotics compared with therapies that included intrauterine
      antibiotics.

PMID- 16428633
TI  - Short communication: suppression of estrous cycles in lactating cows has no
      effect on milk production.
AB  - The decline in milk yield observed after peak production in dairy animals results
      from apoptotic death of mammary epithelial cells. In cows, this decrease in milk
      yield can be accelerated by injection of 17beta-estradiol, thus evoking a
      possible role of estrogens in the regulation of bovine mammary gland involution.
      In nonpregnant cows, mammary involution could be induced or enhanced by the
      return of estrous cycles and the accompanying cyclic peaks of estrogen
      concentration in the serum of lactating animals. To test this hypothesis, we
      inserted implants of a GnRH agonist, deslorelin, in an ear of each cow (n = 10)
      on d 10 and 100 of lactation, to temporarily suppress the return of ovarian
      cycles. Cows were studied from calving to d 210 of lactation. Deslorelin had no
      impact on feed intake or animal health. Deslorelin significantly reduced serum
      concentrations of 17beta-estradiol and progesterone as compared with untreated
      cows (n = 10). Deslorelin had no effect on milk fat and protein, whereas milk
      lactose content was lower in treated cows than in control cows on d 100 of
      lactation. Finally, there was no difference in milk production between the 2
      groups of cows. These results are consistent with previous observations that
      showed that delaying estrous cycles after calving had no effect on milk yield and
      they extend those observations to late lactation. Based on milk production data,
      the estrogen profiles associated with recurring estrous cycles apparently do not
      cause bovine mammary tissue to undergo gradual involution.

PMID- 16428634
TI  - Efficacy of a novel whey protein gel complex to increase the unsaturated fatty
      acid composition of bovine milk fat.
AB  - A novel whey protein emulsion gel (WPEG) complex was developed to protect dietary
      unsaturated fatty acids from rumen biohydrogenation with the goal of modifying
      the fatty acid composition of milk fat. Three experiments were conducted with
      WPEG complexes made from either whey protein concentrate containing 80% crude
      protein, whey protein isolate, or whey protein concentrate high-gel capacity.
      Each experiment lasted 3 wk. All cows received a basal total mixed ration (TMR).
      During wk 1 and 3, all cows received only the TMR. During wk 2, 3 control cows
      received 330 g/d of soybean oil added to the TMR, and the other 3 cows received
      330 g/d of soybean oil in one of the WPEG complexes. During wk 2, C18:2 increased
      from 3.29 to 5.88 g/100 g of fat in Experiment 1, 2.91 to 7.42 g/100 g of fat in
      Experiment 2, and 3.57 to 6.56 g/100 g of fat in Experiment 3 for WPEG cows.
      Fatty acid C18:3 increased from 0.51 to 0.84, 0.52 to 1.15, and 0.51 to 0.97
      g/100 g of fat for Experiments 1, 2, and 3, respectively, for WPEG cows. Higher
      proportions of C18:1 trans-9 in milk fat of control cows compared with WPEG cows
      were seen in all experiments. The proportion of C18:1 trans-11 was also higher in
      control cows in Experiments 1 and 2, but not in Experiment 3. The WPEG complexes
      successfully protected unsaturated fatty acids from rumen biohydrogenation and
      resulted in an increase in the unsaturated fatty acid composition of milk fat
      produced by Holstein cows without increasing the trans 18-carbon monoenes.

PMID- 16428635
TI  - Effects of physically effective fiber on digestive processes and milk fat content
      in early lactating dairy cows fed total mixed rations.
AB  - Data from recent research studies were analyzed quantitatively, and the random
      effect of experiment was assessed to define the physiological responses of dairy
      cows in early lactation to intake of physically effective neutral detergent fiber
      (peNDF). All studies were conducted with lactating Holstein cows (84.8 +/- 3.54
      days in milk) in Latin square designs, and feeds were offered ad libitum as total
      mixed rations (TMR). The peNDF was estimated by 2 measurement techniques, the NDF
      content of TMR multiplied by amount of dry matter (DM) retained on a 1.18-mm
      screen (peNDF(> 1.18)) and NDF content of TMR multiplied by the proportion of DM
      retained by 19- and 8-mm Penn State Particle Separator screens (peNDF(> 8)).
      Other factors, including concentrations of NDF, forage NDF, non-fiber
      carbohydrates, the amount of digestible organic matter of forages (FDOM), and the
      intake of ruminally degradable starch (RDSI) from grain in the diet were also
      investigated. The studied animal response variables included feed intake, ruminal
      fermentation, chewing activity, fiber digestibility, and milk production and
      composition. The ruminal pH (day mean) in this study ranged from 5.30 to 6.59.
      Using peNDF(> 1.18) approach, the requirements for physically effective fiber in
      high-yielding dairy cows fed TMR in an ad libitum intake were estimated to be
      about 19% of ration DM or 4.1 kg/d or 0.6 kg/100 kg of body weight to maintain a
      ruminal pH of about 6.0. When peNDF was measured as peNDF(> 8), ruminal pH
      responded in a quadratic fashion but the confidence of estimation was lower (R(2)
      = 0.27) compared with the peNDF(> 1.18) approach (R(2) = 0.67). Results of these
      data analyses showed that peNDF(> 1.18) provided a satisfactory estimation of the
      mean ruminal pH (R(2) = 0.67) and NDF digestibility (R(2) = 0.56). Furthermore,
      peNDF(> 1.18) was poorly, although positively, correlated to daily chewing (R(2)
      = 0.17), and rumination (R(2) = 0.24) activity. On the other hand, results from
      these analyses showed that milk parameters are less sensitive to the effects of
      dietary peNDF than other variables, such as ruminal pH, chewing activity, and
      fiber digestibility. Dietary FDOM correlated positively (moderately) to ruminal
      pH (R(2) = 0.24), daily chewing (R(2) = 0.23), and rumination (R(2) = 0.29)
      activity, whereas the daily RDSI from grain correlated negatively to ruminal pH
      (R(2) = 0.55) and positively to total volatile fatty acids (R(2) = 0.27).
      Inclusion of FDOM and RDSI from grain along with peNDF(> 1.18) in the models that
      predict rumen pH further improved the accuracy of prediction. This approach
      appeared to further complement the concept of peNDF that does not account for
      differences in ruminal fermentability of feeds.

PMID- 16428636
TI  - Hypocalcemia in dairy cows: meta-analysis and dietary cation anion difference
      theory revisited.
AB  - Data from 137 published trials involving 2,545 calvings were analyzed using
      random effects normal logistic regression models to identify risk factors for
      clinical hypocalcemia in dairy cows. The aim of the study was to examine which
      form, if any, of the dietary cation anion difference (DCAD) equation provided the
      best estimate of milk fever risk and to clarify roles of calcium, magnesium, and
      phosphorus concentrations of prepartum diets in the pathogenesis of milk fever.
      Two statistically equivalent and biologically plausible models were developed
      that predict incidence of milk fever. These models were validated using data from
      37 trials excluded from the original data used to generate the models; missing
      variables were replaced with mean values from the analyzed data. The preferred
      models differed slightly; Model 1 included prepartum DCAD, and Model 2 included
      prepartum dietary concentrations of potassium and sulfur alone, but not sodium
      and chloride. Other factors, included in both models were prepartum dietary
      concentrations of calcium, magnesium, phosphorus; days exposed to the prepartum
      diet; and breed. Jersey cows were at 2.25 times higher risk of milk fever than
      Holstein cows in Model 1. The results support the DCAD theory of greater risk of
      milk fever with higher prepartum dietary DCAD (odds ratio = 1.015). The only DCAD
      equation supported in statistical analyses was (Na(+) + K(+)) - (Cl(-) + S(2-)).
      This finding highlights the difference between developing equations to predict
      DCAD and those to predict milk fever. The results support a hypothesis of a
      quadratic role for Ca in the pathogenesis of milk fever (model 1, odds ratio =
      0.131; Model 2, odds ratio = 0.115). Milk fever risk was highest with a prepartum
      dietary concentration of 1.35% calcium. Increasing prepartum dietary magnesium
      concentrations had the largest effect on decreasing incidence of milk fever in
      both Model 1 (odds ratio = 0.006) and Model 2 (odds ratio = 0.001). Increasing
      dietary phosphorus concentrations prepartum increased the risk of milk fever
      (Model 1, odds ratio = 6.376; Model 2, odds ratio = 9.872). The models presented
      provide the basis for the formulation of diets to reduce the risk of milk fever
      and strongly support the need to evaluate macro mineral nutrition apart from DCAD
      of the diet.

PMID- 16428637
TI  - Effect of dietary vitamin E on rumen biohydrogenation pathways and milk fat
      depression in dairy cows fed high-fat diets.
AB  - Six lactating Holstein cows were assigned to a replicated Latin square design to
      test the effect of dietary vitamin E on milk fat depression and on the increased
      production of milk trans-10 C18:1 classically observed when feeding high doses of
      unsaturated fatty acids with low-fiber diets. Two diets (linseed diet and linseed
      diet + 12,000 IU of vitamin E/d) were compared during 2 periods of 21 d. The
      linseed diet presented a forage-to-concentrate ratio of 50:50 and contained
      extruded linseed (1.86 kg/d) and linseed oil (190 g/d). It was conceived to favor
      the "trans-11 to trans-10 shift" (low structural value and high level of
      unsaturated fatty acids). Milk yield and protein content were not affected by the
      diets. Milk of cows fed the linseed diet presented the typical symptoms of milk
      fat depression associated with a shift in biohydrogenation pathways: low fat
      content and high level of trans-10 C18:1. However, the high dose of dietary
      vitamin E provided significantly increased milk fat content (by 17.93%) and yield
      (by 15.56%) and decreased trans-10 C18:1 content (by 47.06%). In addition, it
      managed to significantly increase the daily yields of vaccenic (by 102.56%) and
      rumenic acids (by 56.67%). However, the sequence of administration of vitamin E
      influenced its effect, as vitamin E seemed to be more active in limiting the
      "trans-11 to trans-10 shift" when it was incorporated in the diet simultaneously
      with the fat. Once the shift had occurred, the subsequent addition of vitamin E
      was no longer able to completely counteract this process.

PMID- 16428638
TI  - Effects of short-term glucagon administration on gluconeogenic enzymes in the
      liver of midlactation dairy cows.
AB  - During lactation, the dairy cow experiences an increased demand for glucose to
      support milk production. Increased glucose demand can be met through increased
      capacity for gluconeogenesis, increased supply of glucose precursors, or a
      combination of both processes. Glucagon, a key hormone in glucose homeostasis,
      acts to promote gluconeogenesis and increase glucose output from liver. The
      objective of this study was to determine the effect of short-term administration
      of glucagon on expression of gluconeogenic enzymes in lactating dairy cattle.
      Sixteen multiparous Holstein cows were selected from the Purdue University Animal
      Sciences Dairy Research Center herd. Cows were stratified on the basis of milk
      production and days in milk and randomly assigned to either a saline or glucagon
      injection group (n = 8 per group). Cows were injected subcutaneously at -21, -14,
      -7, and 0 h relative to final glucagon and saline injections with either 3.75 mg
      of lyophilized bovine glucagon (15 mg/d) dissolved in 60 mL of 0.15 M NaCl (pH
      10.25) or 60 mL of 0.15 M NaCl. Liver biopsy samples were obtained 1 wk before
      injection to establish baseline values and at 3 h after cows received final
      glucagon and saline injections. Biopsy samples were analyzed for mRNA abundance,
      enzyme activity, protein abundance, and in vitro measures of gluconeogenesis.
      Glucagon did not alter pyruvate carboxylase or cytosolic phosphoenolpyruvate
      carboxykinase (PEPCK) mRNA abundance, enzyme activity, or protein abundance,
      although there was a tendency for greater mRNA expression with the glucagon
      treatment (4.69 vs. 6.78, arbitrary units). Glucagon injections did not change
      mitochondrial PEPCK mRNA expression. Gluconeogenesis from 2.5 mM [2
      (14)C]propionate and 2.0 mM [U-(14)C]lactate was similar in liver biopsy samples
      from glucagon-treated and control cows. There was no effect of glucagon on dry
      matter intake and milk production. Glucose, nonesterified fatty acids, beta
      hydroxybutyrate acid, and insulin were not altered by glucagon. Blood glucagon
      was elevated, 76.09 vs. 96.14 pg/mL, for cows receiving glucagon injections. The
      data indicate that 24-h administration of glucagon does not alter cytosolic PEPCK
      mRNA expression or result in immediate alterations in total PEPCK enzyme activity
      and gluconeogenic capacity.

PMID- 16428639
TI  - Effect of prepartum dietary calcium on intake and serum and urinary mineral
      concentrations of cows.
AB  - Nine multiparous and 12 primiparous cows were fed diets containing an anionic
      salt supplement and moderate Ca (0.99%) or high Ca (1.50%) concentrations for 21
      d prepartum to determine the effects of dietary Ca concentration on serum and
      urine electrolytes and on postpartum intake and milk yield. Blood samples were
      collected during 21 to 1 d prepartum, 0 to 2 d postpartum, and 3 to 21 d
      postpartum. Dietary cation-anion difference (DCAD) for prepartum diets was
      approximately -6 mEq/100 g of dry matter (Na + K - Cl - S). Immediately
      postpartum, cows were fed diets with positive DCAD with greater than 1.00% Ca
      concentration. Mean serum Ca concentrations 21 to 1 d prepartum, 0 to 2 d
      postpartum, and 3 to 21 d postpartum were 9.62, 8.41, and 9.38 mg/dL. There were
      no treatment effects on serum Ca concentration. Mean serum Ca concentration was
      higher for primiparous than multiparous cows (9.34 vs. 8.93 mg/dL) for the trial
      and at calving (8.77 vs. 8.13 mg/dL). Mean serum HCO(3)(-) and urinary pH,
      respectively, were 20.32 mEq/L and 5.67 prepartum, 25.82 mEq/L and 7.62 at
      calving, and 26.08 mEq/L and 8.25 postpartum. No differences due to treatment
      were observed for serum and urinary concentrations of HCO(3)(-), pH, Mg, Na, K,
      and Cl. Milk yield was similar for 0.99 and 1.50% Ca treatments (22.8 and 20.7
      kg/d). Diets containing 0.99 or 1.5% Ca maintained serum Ca at adequate levels
      around parturition and resulted in similar dry matter intake and postpartum milk
      yield.

PMID- 16428640
TI  - Examination of the persistency of milk fatty acid composition responses to fish
      oil and sunflower oil in the diet of dairy cows.
AB  - Based on the potential benefits of cis-9, trans-11 conjugated linoleic acid (CLA)
      for human health, there is a need to develop effective strategies for enhancing
      milk fat CLA concentrations. Levels of cis-9, trans-11 CLA in milk can be
      increased by supplements of fish oil (FO) and sunflower oil (SO), but there is
      considerable variation in the response. Part of this variance may reflect time
      dependent ruminal adaptations to high levels of lipid in the diet, which lead to
      alterations in the formation of specific biohydrogenation intermediates. To test
      this hypothesis, 16 late lactation Holstein-British Friesian cows were used in a
      repeated measures randomized block design to examine milk fatty acid composition
      responses to FO and SO in the diet over a 28-d period. Cows were allocated at
      random to corn silage-based rations (8 per treatment) containing 0 (control) or
      45 g of oil supplement/kg of dry matter consisting (1:2; wt/wt) of FO and SO
      (FSO), and milk composition was determined on alternate days from d 1. Compared
      with the control, the FSO diet decreased mean dry matter intake (21.1 vs. 17.9
      kg/d), milk fat (47.7 vs. 32.6 g/kg), and protein content (36.1 vs. 33.3 g/kg),
      but had no effect on milk yield (27.1 vs. 26.4 kg/d). Reductions in milk fat
      content relative to the FSO diet were associated with increases in milk trans-10
      18:1, trans-10, cis-12 CLA, and trans-9, cis-11 CLA concentrations (r(2) = 0.74,
      0.57, and 0.80, respectively). Compared with the control, the FSO diet reduced
      milk 4:0 to 18:0 and cis 18:1 content and increased trans 18:1, trans 18:2, cis
      9, trans-11 CLA, 20:5 n-3, and 22:6 n-3 concentrations. The FSO diet caused a
      rapid elevation in milk cis-9, trans-11 CLA content, reaching a maximum of 5.37
      g/100 g of fatty acids on d 5, but these increases were transient, declining to
      2.35 g/100 g of fatty acids by d 15. They remained relatively constant
      thereafter. Even though concentrations of trans-11 18:1 followed the same pattern
      of temporal changes as cis-9, trans-11 CLA, the total trans 18:1 content of FSO
      milk was unchanged because of the concomitant increases in the concentration of
      other isomers (Delta(4-10) and Delta(12-15)), predominantely trans-10 18:1. In
      conclusion, supplementing diets with FSO enhances milk fat cis-9, trans-11 CLA
      content, but the high level of enrichment declines because of changes in ruminal
      biohydrogenation that result in trans-10 replacing trans-11 as the major 18:1
      biohydrogenation intermediate formed in the rumen.

PMID- 16428641
TI  - Effect of safflower oil, flaxseed oil, monensin, and vitamin E on concentration
      of conjugated linoleic acid in bovine milk fat.
AB  - Conjugated linoleic acid (CLA) refers to a mixture of conjugated octadecadienoic
      acids of predominantly ruminant origin. The main isomer in bovine milk fat is the
      cis-9, trans-11 CLA. Interest in CLA increased after the discovery of its health
      promoting properties, including potent anticarcinogenic activity. Two experiments
      were conducted to evaluate dietary strategies aimed at increasing the
      concentration of CLA in bovine milk fat. Both experiments were organized as a
      randomized complete block design with a repeated measures treatment structure. In
      Experiment 1, 28 Holstein cows received either a control diet or one of 3
      treatments for a period of 2 wk. The control diet consisted of 60% forage (barley
      silage, alfalfa silage, and alfalfa hay) and 40% concentrate on a dry matter (DM)
      basis, fed as a total mixed ration (TMR). The concentrate was partially replaced
      in the treatment groups with 24 ppm of monensin (MON), 6% of DM safflower oil
      (SAFF), or 6% of DM safflower oil plus 24 ppm of monensin (SAFF/M). Average cis
      9, trans-11 CLA levels in milk fat after 2 wk of feeding were 0.45, 0.52, 3.36,
      and 5.15% of total fatty acids for control, MON, SAFF, and SAFF/M, respectively.
      In Experiment 2, 62 Holstein cows received either a control diet or one of 5
      treatment diets for a period of 9 wk. The control diet consisted of 60% forage
      (barley silage, alfalfa silage, and alfalfa hay) and 40% concentrate on a DM
      basis, fed as a TMR. The concentrate was partially replaced in the treatment
      groups with 6% of DM safflower oil (SAFF), 6% of DM safflower oil plus 150 IU of
      vitamin E/kg of DM (SAFF/E), 6% of DM safflower oil plus 24 ppm of monensin
      (SAFF/M), 6% of DM safflower oil plus 24 ppm of monensin plus 150 IU of vitamin
      E/kg of DM (SAFF/ME), or 6% of DM flaxseed oil plus 150 IU of vitamin E/kg of DM
      (FLAX/E). Average cis-9, trans-11 CLA levels during the treatment period were
      0.68, 4.12, 3.48, 4.55, 4.75, and 2.80% of total fatty acids for control, SAFF,
      SAFF/E, SAFF/M, SAFF/ME, and FLAX/E, respectively. The combination of safflower
      oil with monensin was particularly effective at increasing milk fat CLA. The
      addition of vitamin E to the diet partially prevented the depression in milk fat
      associated with oilseed feeding, but had no significant effect on the
      concentration of CLA in milk.

PMID- 16428642
TI  - Changing dietary cation-anion difference for dairy cows fed with two contrasting
      levels of concentrate in diets.
AB  - High-producing dairy cows are commonly fed diets containing a high proportion of
      rapidly degradable starch, which can cause subacute acidosis and reduce dry
      matter (DM) intake. Because of the properties of nonmetabolizable cations and
      anions, increasing the dietary cation-anion difference (DCAD = Na + K - Cl - S in
      mEq/kg of DM) may prevent a drop in DM intake. To test this hypothesis, 48
      Holstein cows were blocked into 2 groups of 24 and assigned to two 3 x 3 Latin
      squares in a split-plot design. Each group received one level of concentrate at
      either 20% or 40% on a dry matter (DM) basis. The diet containing 20% concentrate
      was formulated to supply 4% rapidly degradable starch, whereas the diet
      containing 40% concentrate supplied 22% rapidly degradable starch. Diets in each
      square were formulated to provide a DCAD of 0, 150, or 300 mEq/kg of DM. The 3
      values were obtained by manipulating Na and Cl contents. Intake, 4% fat-corrected
      milk yield, and milk fat percentage, as well as blood nonesterified fatty acids
      and beta-hydroxybutyrate increased with DCAD, but only on the diet providing 40%
      concentrate. The yield of trans-10 C(18:1) and odd-chain fatty acids decreased
      with increasing DCAD, whereas trans-11 C(18:1) increased. Again, this occurred
      only with the diet providing 40% concentrate. Blood pH and HCO(3) concentration
      increased along with DCAD, irrespective of the concentrate level. A positive DCAD
      led to increasing DM intake and fat-corrected milk yield in dairy cows fed highly
      degradable diets. The mechanism involved may be a localized rumen buffering
      effect, together with the ability of positive DCAD to maintain blood acid-base
      status in cows faced with a massive acid input.

PMID- 16428643
TI  - Plant extracts affect in vitro rumen microbial fermentation.
AB  - Different doses of 12 plant extracts and 6 secondary plant metabolites were
      incubated for 24 h in diluted ruminal fluid with a 50:50 forage:concentrate diet.
      Treatments were: control (no additive), plant extracts (anise oil, cade oil,
      capsicum oil, cinnamon oil, clove bud oil, dill oil, fenugreek, garlic oil,
      ginger oil, oregano oil, tea tree oil, and yucca), and secondary plant
      metabolites (anethol, benzyl salicylate, carvacrol, carvone, cinnamaldehyde, and
      eugenol). Each treatment was supplied at 3, 30, 300, and 3,000 mg/L of culture
      fluid. At 3,000 mg/L, most treatments decreased total volatile fatty acid
      concentration, but cade oil, capsicum oil, dill oil, fenugreek, ginger oil, and
      yucca had no effect. Different doses of anethol, anise oil, carvone, and tea tree
      oil decreased the proportion of acetate and propionate, which suggests that these
      compounds may not be nutritionally beneficial to dairy cattle. Garlic oil (300
      and 3,000 mg/L) and benzyl salicylate (300 and 3,000 mg/L) reduced acetate and
      increased propionate and butyrate proportions, suggesting that methane production
      was inhibited. At 3,000 mg/L, capsicum oil, carvacrol, carvone, cinnamaldehyde,
      cinnamon oil, clove bud oil, eugenol, fenugreek, and oregano oil resulted in a 30
      to 50% reduction in ammonia N concentration. Careful selection and combination of
      these extracts may allow the manipulation of rumen microbial fermentation.

PMID- 16428644
TI  - Bivariate analysis of number of services to conception and days open in Norwegian
      red using a censored threshold-linear model.
AB  - A bivariate censored threshold-linear model was used to study genetic parameters
      of number of services to conception (STC) and days open (DO) in first-lactation
      Norwegian Red (NRF) cows. Records of 1,454,916 NRF cows, with a first
      insemination from 1980 to 2004, were analyzed. It was assumed that every cow had
      at least a first insemination. The number of inseminations was recorded until a
      cow conceived or was culled, whichever occurred first. If a cow was culled before
      conception, it was considered censored at the number of services until culling
      was recorded. Twenty-one percent of cows were censored for both STC and DO. Using
      an univariate probit link function for STC, unobserved liabilities to STC and DO
      were modeled jointly as a linear function of age at first calving, month-year at
      first calving, herd-5-yr period, sire of cow and residual effects. Heritability
      of liability to STC and DO was 4% for each trait. The genetic and residual
      correlations between STC and DO were 0.77 and 0.68, respectively. There has been
      little or no genetic change for DO, whereas STC had favorable genetic and
      phenotypic trends.

PMID- 16428645
TI  - Short communication: genetic correlation between test-day electrical conductivity
      of milk and mastitis.
AB  - Electrical conductivity (EC) of milk is an indicator of mastitis. If EC shows
      genetic variation and is genetically correlated to mastitis, it could be used in
      a breeding program that includes selection for improved mastitis resistance. In
      this study, daily records of EC and mastitis from about 1,500 Holstein cows were
      analyzed. A bivariate animal model was used for estimation of (co)variance
      components, including fixed effects of age of calving, herd-test-day, and days in
      milk, in addition to random additive genetic effects and permanent environmental
      effects. For EC, the estimated heritability was moderate (0.22 to 0.39), whereas
      for mastitis, the heritability was low (0.013). The genetic correlation between
      EC and mastitis was estimated to be 0.75, and genetic improvement of mastitis
      resistance should be feasible through selection for reduced EC.

PMID- 16428646
TI  - Detection of quantitative trait loci affecting milk production traits on bovine
      chromosome 6 in a Chinese Holstein population by the daughter design.
AB  - Fourteen microsatellite markers with a coverage of 63.5 cM on bovine chromosome 6
      were selected, and 26 sire families with 2,260 daughters were analyzed for
      mapping quantitative trait loci (QTL) affecting 5 milk production traits in a
      Chinese Holstein population. In the analyses across 26 families and within the
      largest significant families with a one-QTL model fitted, a QTL near BMS470 was
      detected that affected fat yield at the 5% experiment-wide significance level.
      When a 2-QTL model was fitted in the across-family analysis, it was found that
      there might exist 2 QTL affecting the 3 yield traits, although the exact or
      empirical thresholds for the significance testing were unknown. In all analyses,
      the results for milk yield and protein yield were generally consistent, which
      might have resulted from the same genetic background for milk and protein yield.

PMID- 16428647
TI  - Genetic parameters for functional traits in dairy cattle from daily random
      regression models.
AB  - The objective of the research was to estimate genetic parameters, such as
      heritabilities and genetic correlations, using daily test day data for milk yield
      (MY), milking speed (MS), dry matter intake (DMI), and body weight (BW) using
      random regression methodology. Data were from first lactation dairy cows (n =
      320) from the Chamau research farm of the Swiss Federal Institute of Technology,
      Switzerland over the period from April 1994 to 2004. All traits were recorded
      daily using automated machines. Estimated heritabilities (h(2)) varied from 0.18
      to 0.30 (mean h(2) = 0.24) for MY, 0.003 to 0.098 (mean h(2) = 0.03) for MS, 0.22
      to 0.53 (mean h(2) = 0.43) for BW, and 0.12 to 0.34 (mean h(2) = 0.23) for DMI. A
      permanent environmental effect was included in both the univariate and bivariate
      models, but was assumed constant in estimating some genetic correlations because
      of convergence problems. Estimated genetic correlations varied from 0.31 to 0.41
      between MY and MS, from -0.47 to 0.29 between MY and DMI, from -0.60 to 0.54
      between MY and BW, from 0.17 to 0.26 between MS and DMI, from -0.18 to 0.25
      between MS and BW, and from -0.89 to 0.29 between DMI and BW. Genetic
      correlations for MY, MS, DMI, and BW from calving to midlactation decreased
      similarly to 0.40, 0.36, 0.14, and 0.36 and, at the end of the lactation,
      decreased to -0.06, 0.23, -0.07, and 0.09, respectively. Daily genetic variance
      covariance of many functional traits are reported for the first time and will be
      useful when constructing selection indexes for more than one trait based on
      longitudinal genetic parameters.

PMID- 16428648
TI  - Two mathematical programming models of cheese manufacture.
AB  - The standardization problem faced by cheese makers is formulated as a nonlinear
      programming problem using the assumptions of the Van Slyke cheese yield formula.
      The objective function of the model is to minimize the net cost of producing a
      given quantity of cheese subject to a set of production constraints. An
      approximation of the standardization problem formulated as a linear programming
      problem is also presented. Two different approaches to finding a solution are
      provided. The model is implemented in Microsoft Excel and solved with the
      standard add-in solver available in that program. An example is provided to
      contrast the difference between the nonlinear programming and its linear
      approximation, and a second example is used to illustrate the yield implications
      of ultrafiltered milk protein products in Cheddar cheese production.
      Additionally, a method for pricing inputs using the sensitivity analysis
      generated by the solver is demonstrated.

PMID- 16428649
TI  - Practice Standards Scheme: public launch set for March 30.

PMID- 16428657
TI  - Equine disease surveillance, July to September 2005.

PMID- 16428661
TI  - Results of allergen-specific immunotherapy in 117 dogs with atopic dermatitis.
AB  - The success of the treatment of 117 dogs with atopic dermatitis with allergen
      specific immunotherapy for up to 48 months was assessed. An excellent response
      (remission with exclusive immunotherapy) was recorded in 18 of the dogs, a good
      response (more than 50 per cent reduction in medication and improvement of
      clinical signs) was recorded in 57, a moderate response was recorded in 24 and a
      poor response in 18. The mould antigens in the allergen extract were stored in a
      separate vial before administration and the success rate of the immunotherapy
      including mould antigens was much higher than in an earlier study in which mould
      and pollen antigens had been stored in one vial. The success rate was not
      affected significantly by the age of the dogs when the disease developed, or by
      their age or the period for which they had shown clinical signs when the
      treatment began; it was also unaffected by whether pollens, moulds or dust mites
      were used as antigens, or by whether the offending allergens had been identified
      by intradermal testing or by serum testing for allergen-specific immunoglobulin
      E.

PMID- 16428662
TI  - Postal survey of the population of South American camelids in the United Kingdom
      in 2000/01.
AB  - The members of the two leading British camelid breeders associations were
      surveyed by means of a postal questionnaire between December 2000 and January
      2001; 696 questionnaires were posted and 218 usable responses were returned. A
      total of 3520 camelids were recorded, of which 2719 (77.2 per cent) were alpacas
      (Lama pacos) and 726 (20.6 per cent) were llamas (Lama glama). Ninety-four per
      cent of the camelid herds were of one species, and 70 per cent of the animals
      were kept for more than one purpose. Camelids imported from South America were
      present on 45 per cent of the units surveyed. Husbandry procedures and preventive
      health measures were uniform; 92.2 per cent of the animals were kept on pasture
      all year round, 99 per cent were supplemented with hay and 97.7 per cent with
      concentrate feed; 88.1 per cent were vaccinated against clostridial disease with
      a multivalent vaccine licensed for sheep, and 96.3 per cent were treated
      periodically with anthelmintic drugs. During 2000, ill health, other than
      dermatological conditions, was reported by 24.3 of respondents, and 32 different
      conditions were described. Skin disease was reported by 51 per cent of breeders.
      Zinc deficiency was diagnosed presumptively as the cause of skin disease by 31.9
      per cent of the respondents, and ectoparasitism by 26.4 per cent. Of those who
      treated a skin condition, 71.9 per cent reported an improvement, but less than
      half of them considered the improvement to have been permanent.

PMID- 16428664
TI  - Inactivation of BSE infectivity on chips of bone by autoclaving during the
      manufacture of gelatine.

PMID- 16428663
TI  - Canine adenovirus type 2 infection in four puppies with neurological signs.
AB  - Four nine- to 11-week-old puppies developed respiratory and neurological signs
      due to an infection with canine adenovirus type 2 (cav-2); three of these were
      euthanased. They had moderate, diffuse pneumonia but there were no histological
      abnormalities in the central nervous system. Adenovirus-specific nucleic acid was
      detected by pcr in samples of lung and brain and the amplified product was 99.8
      per cent homologous with the cav-2 reference strain Toronto a26/61. The positive
      pcr result was confirmed by in situ hybridisation in samples of lung, liver and
      spleen, but not in brain, and cav was isolated in cell culture from lung
      material; pcrs for canine distemper virus and canine herpesvirus-specific nucleic
      acids were negative, but large amounts of Bordetella bronchiseptica were isolated
      from lung material.

PMID- 16428665
TI  - Bifid tongue and mandibular cleft in three mule foals.

PMID- 16428666
TI  - Nasal infestation with the leech Dinobdella ferox in a domestic shorthair cat.

PMID- 16428667
TI  - Relationship between outbreaks of blackleg in cattle and annual rainfall in
      Zaria, Nigeria.

PMID- 16428668
TI  - Pleural and peritoneal tetrathyridiosis in a peafowl.

PMID- 16428669
TI  - Isolation of avian influenza virus in Bulgaria.

PMID- 16428670
TI  - Udder singeing in dairy cows.

PMID- 16428671
TI  - Presence of PRRSV in wild boar in Italy.

PMID- 16428672
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16428673
TI  - Seeing stars.

PMID- 16428675
TI  - Treatment of corneal ulcers in dogs.

PMID- 16428676
TI  - Slaughter of poultry.

PMID- 16428677
TI  - Expression of concern: Sudbo J et al. DNA content as a prognostic marker in
      patients with oral leukoplakia. N Engl J Med 2001;344:1270-8 and Sudbo J et al.
      the influence of resection and aneuploidy on mortality in oral leukoplakia. N
      Engl J Med 2004;350:1405-13.

PMID- 16428678
TI  - Comments on "shift from biliary to urinary elimination of acetaminophen
      glucuronide in acetaminophen-pretreated rats".

PMID- 16428679
TI  - Plans for new conjoint certificate of added qualifications in hospice and
      palliative medicine.

PMID- 16428680
TI  - Navigation in neurologic localization: web site launch.

PMID- 16428683
TI  - Computer animation and improved student comprehension of basic science concepts.
AB  - Many medical students have difficulty learning basic science, either because they
      find the material challenging to comprehend or because they believe it has
      limited clinical application. Computer-assisted instruction (CAI)--ie, computer
      animation--can clarify instruction by allowing students to visualize complex,
      dynamic processes in an interesting presentation. At West Virginia School of
      Osteopathic Medicine (WVSOM) in Lewisburg, a series of computer animations have
      been developed to present concepts in molecular and cellular biology. The author
      conducted an investigation to compare the efficacy of one representative computer
      animation with that of traditional textbook material. The subjects were 22
      students who had been admitted to WVSOM but who had not yet begun classes. The
      experimental design of the study consisted of a prelesson test, a lesson, and a
      postlesson test. The lesson explained the process of deoxyribonucleic acid (DNA)
      replication using either a computer animation (n=12) or a chapter from a textbook
      (n=10). Lesson comprehension as measured by the tests was significantly higher
      for subjects who used the computer animation than for subjects who used the
      textbook (P<.01). Furthermore, reviewing the text after studying with the
      computer animation did not raise test scores, suggesting that the animation was
      sufficient for learning and the text was unnecessary. After the study, a majority
      of subjects indicated a preference for the animation over the text. These results
      demonstrate that CAI can be an effective tool for relating basic science to
      medical students by improving comprehension and eliciting interest in the
      lessons.

PMID- 16428684
TI  - Beating asthma: a community-based asthma education initiative.
AB  - Beating Asthma is a community-based educational intervention designed to empower
      people with asthma by providing them with information about their pulmonary
      disease. The project consists of a series of three lectures delivered in a single
      2-hour evening program by a pulmonologist, a health educator, and a licensed
      clinical psychologist. Surveys were distributed to participants before and after
      the program to assess general knowledge of asthma, the disease's pathophysiology,
      and asthma-management skills. Seventy-eight (77%) of the 101 families
      participating in the event completed both questionnaires. Regression model
      analysis of survey results showed that participants with the lowest scores before
      intervention achieved the greatest gains after intervention (P<.001). Analysis of
      the three topic areas revealed that only the subscore for disease management
      differed significantly from zero (P<.001). The authors assess the quality and
      usefulness of the survey instrument and the lecture content for future use.

PMID- 16428685
TI  - Magnetic resonance spectroscopy as an imaging tool for cancer: a review of the
      literature.
AB  - OBJECTIVES: To review the use of magnetic resonance spectroscopy (MRS) as a
      clinical tool in the identification of cerebral neoplasia type and grade, as well
      as neoplasia in the prostate, colon, breast, cervix, pancreas, and esophagus.
      Also, to review how clinicians are using MRS for surgical planning and
      longitudinal evaluation of tumors after treatment. DATA SOURCES: Studies and
      clinical case reports published within the previous 10 years, targeting
      publications in radiology and oncology journals within the previous 3 years.
      Sources identified via MEDLINE and PubMed databases. STUDY SELECTION: Studies
      that contrasted MRS with conventional diagnostic and prognostic methods were
      considered to yield the most relevant data for this review. Studies discussing
      cancer staging and grading were also examined to help determine clinical
      significance of MRS. DATA SYNTHESES: A review of the literature reveals that,
      although MRS has mainly been used in diagnostics and tumor evaluation for brain
      cancer, it is becoming an increasingly important adjunct to conventional
      diagnostic and monitoring procedures for cancer of the prostate, colon, breast,
      cervix, pancreas, and esophagus. CONCLUSIONS: The clinical usefulness of MRS has
      yet to be fully substantiated. As MRS availability and access increases,
      appropriate evaluations of its strengths and weaknesses will be made. The authors
      conclude that research to date and primary observation indicate that MRS is a
      promising clinical tool for oncologic management of patients.

PMID- 16428688
TI  - Introduction to the diagnosis and management of cough: ACCP evidence-based
      clinical practice guidelines.

PMID- 16428686
TI  - Diagnosis and management of cough executive summary: ACCP evidence-based clinical
      practice guidelines.

PMID- 16428689
TI  - Methodology and grading of the evidence for the diagnosis and management of
      cough: ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVES: To assemble a multidisciplinary, geographically diverse panel of
      experts in the diagnosis and treatment of cough with the intention of developing
      clinically relevant practice guidelines for pulmonary and primary care
      physicians, including recommendations covering many etiologies of cough, adult
      and pediatric evaluation and treatment, and empiric yet integrative algorithms
      for the management of the patient with cough. METHODS: The Duke University Center
      for Clinical Health Policy Research was selected to review and summarize the
      current evidence in this area. The expert panel established clinical
      recommendations and algorithms founded on the synthesis of this evidence.
      CONCLUSIONS: This section describes the approach used to develop the guidelines,
      including identifying, evaluating, and synthesizing the evidence, assessing the
      strength of evidence pertinent to individual guidelines, and grading the
      guideline recommendations.

PMID- 16428690
TI  - Anatomy and neurophysiology of the cough reflex: ACCP evidence-based clinical
      practice guidelines.
AB  - OBJECTIVES: To describe the anatomy and neurophysiology of the cough reflex.
      METHODS: A review of the literature was carried out using PubMed and the ISI Web
      of Knowledge from 1951 to 2004. Most of the referenced studies were carried out
      in animals CONCLUSIONS: Studies carried out in animals provide suggestive but
      inconclusive evidence that C-fibers and rapidly adapting receptors (RARs) arising
      from the vagus nerves mediate coughing. Recent studies also have suggested that a
      vagal afferent nerve subtype that is not readily classified as a RAR or a C-fiber
      may play an important role in regulating cough. Afferent nerves innervating other
      viscera, as well as somatosensory nerves innervating the chest wall, diaphragm,
      and abdominal musculature also likely play a less essential but important
      accessory role in regulating cough. The responsiveness and morphology of the
      airway vagal afferent nerve subtypes and the extrapulmonary afferent nerves that
      regulate coughing are described.

PMID- 16428691
TI  - Global physiology and pathophysiology of cough: ACCP evidence-based clinical
      practice guidelines.
AB  - OBJECTIVE: The anatomy and neurophysiology of cough has been reviewed in the
      preceding section. The objective of this section is to describe how the varied
      anatomic components of the respiratory system work in concert to produce an
      effective cough. METHODS: This was accomplished by reviewing (1) the factors
      needed to produce effective cough pressures and gas velocity in the airways, and
      (2) the salient features of the interaction between the airflow generated during
      a cough and the mucus that lines the tracheobronchial tree. The MEDLINE database
      was searched for this review, and the search consisted of studies published in
      English between 1960 and April 2004. Search terms were "cough mechanics" and
      "cough physiology." RESULTS: Inhaling to high lung volumes and glottic closure
      prior to the expiratory phase of cough facilitate the generation of high
      intrathoracic pressures. These high intrathoracic pressures (1) provide the
      driving force for airstream flow during cough and (2) dynamically compress the
      central airways, which further enhances the cough airstream velocity.
      CONCLUSIONS: High intrathoracic pressures are needed to generate the requisite
      cough expiratory flows and airstream velocities. However, cough may be effective
      in individuals with mild-to-moderate degrees of respiratory muscle weakness, as
      only modest increases in intrathoracic pressure are needed to dynamically
      compress the large intrathoracic airways and increase cough flow velocity.

PMID- 16428692
TI  - Complications of cough: ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVES: To review the spectrum and frequency of complications associated with
      coughing. DESIGN/METHODOLOGY: Ovid MEDLINE literature review (through March 2004)
      for all studies published in the English language, including case series and case
      reports, since 1966 using the MeSH terms "cough" and "complications." RESULTS:
      The complications of cough appear to stem from physiologic events. The magnitude
      of pressures, velocities, and energy that is generated during vigorous coughing
      allow coughing to be an effective means of clearing the airways of excessive
      secretions and foreign material, and providing cardiopulmonary resuscitation;
      however, they can also cause a variety of profound physical and psychosocial
      complications. The adverse occurrences include cardiovascular, constitutional,
      GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial,
      respiratory, and skin complications, and a decrease in health-related quality of
      life. CONCLUSIONS: Knowledge of the spectrum of complications should enable
      clinicians to appreciate (1) the impact of cough on patients, (2) why it is
      imperative to exhaust all possible diagnostic and therapeutic options to
      eliminate cough, and (3) why it is inappropriate to minimize a patient's
      complaint of cough and/or advise him/her to "live with it."

PMID- 16428693
TI  - Overview of common causes of chronic cough: ACCP evidence-based clinical practice
      guidelines.
AB  - OBJECTIVE: To review the literature on the most common causes of chronic cough.
      METHODS: MEDLINE was searched (through May 2004) for studies published in the
      English language since 1980 on human subjects using the medical subject heading
      terms "cough," "causes of cough," and "etiology of cough." Case series and
      prospective descriptive clinical trials were selected for review. Also obtained
      were any references from these studies that were pertinent to the topic RESULTS:
      Upper airway cough syndrome (UACS) due to a variety of rhinosinus conditions,
      previously referred to as postnasal drip syndrome, asthma, nonasthmatic
      eosinophilic bronchitis (NAEB), and gastroesophageal reflux disease (GERD) are
      the most common causes of chronic cough. Each of these diagnoses may be present
      alone or in combination and may be clinically silent apart from the cough itself.
      CONCLUSION: In the absence of evidence for the presence of another disorder, an
      approach focused on detecting the presence of UACS, asthma, NAEB, or GERD, alone
      or in combination, is likely to have a far higher yield than routinely searching
      for relatively uncommon or obscure diagnoses.

PMID- 16428694
TI  - Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously
      referred to as postnasal drip syndrome): ACCP evidence-based clinical practice
      guidelines.
AB  - OBJECTIVE: To review the literature on postnasal drip syndrome (PNDS)-induced
      cough and the various causes of PNDS. Hereafter, PNDS will be referred to as
      upper airway cough syndrome (UACS). METHODS: MEDLINE search (through May 2004)
      for studies published in the English language since 1980 on human subjects using
      the medical subject heading terms "cough," "causes of cough," "etiology of
      cough," "postnasal drip," "allergic rhinitis," "vasomotor rhinitis," and "chronic
      sinusitis." Case series and prospective descriptive clinical trials were selected
      for review. Also, any references from these studies that were pertinent to the
      topic were obtained. RESULTS: In multiple prospective, descriptive studies of
      adults, PNDS due to a variety of upper respiratory conditions has been shown
      either singly or in combination with other conditions, to be the most common
      cause of chronic cough. The symptoms and signs of PNDS are nonspecific, and a
      definitive diagnosis of PND-induced cough cannot be made from the medical history
      and physical examination findings alone. Furthermore, the absence of any of the
      usual clinical findings does not rule out a response to treatment that is usually
      effective for PND-induced cough. The differential diagnosis of PNDS-induced cough
      includes allergic rhinitis, perennial nonallergic rhinitis, postinfectious
      rhinitis, bacterial sinusitis, allergic fungal sinusitis, rhinitis due to
      anatomic abnormalities, rhinitis due to physical or chemical irritants,
      occupational rhinitis, rhinitis medicamentosa, and rhinitis of pregnancy. Because
      of a high prevalence of upper respiratory symptoms associated with
      gastroesophageal reflux disease (GERD), GERD may occasionally mimic PNDS. A
      crucial unanswered question is whether the conditions listed above actually
      produce cough through a final common pathway of PND or whether, in fact, in some
      circumstances they cause irritation or inflammation of upper airway structures
      that directly stimulate cough receptors and produce cough independently of or in
      addition to any associated PND. CONCLUSION: PNDS (ie, UACS) secondary to a
      variety of rhinosinus conditions is the most common cause of chronic cough.
      Because it is unclear whether the mechanisms of cough are the PND itself or the
      direct irritation or inflammation of the cough receptors located in the upper
      airway, the guideline committee has decided that, pending further data that
      address this difficult question, the committee unanimously recommends that the
      term upper airway cough syndrome be used in preference to postnasal drip syndrome
      when discussing cough associated with upper airway conditions.

PMID- 16428695
TI  - Cough and the common cold: ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVE: To review the literature on cough and the common cold. METHODS:
      MEDLINE was searched through May 2004 for studies published in the English
      language since 1980 on human subjects using the medical subject heading terms
      "cough" and "common cold." Selected case series and prospective descriptive
      clinical trials were reviewed. Additional references from these studies that were
      pertinent to the topic were also reviewed. RESULTS: Based on extrapolation from
      epidemiologic data, the common cold is believed to be the single most common
      cause of acute cough. The most likely mechanism is the direct irritation of upper
      airway structures. It is also clear that viral infections of the upper
      respiratory tract that produce the common cold syndrome frequently produce a
      rhinosinusitis. In the setting of a cold, the presence of abnormalities seen on
      sinus roentgenograms or sinus CT scans are frequently due to the viral infection
      and are not diagnostic of bacterial sinus infection. CONCLUSION: Cough due to the
      common cold is probably the most common cause of acute cough. In a significant
      subset of patients with "postinfectious" cough, the etiology is probably an
      inflammatory response triggered by a viral upper respiratory infection (ie, the
      common cold). The resultant subacute or chronic cough can be considered to be due
      to an upper airway cough syndrome, previously referred to as postnasal drip
      syndrome. This process can be self-perpetuating unless interrupted with active
      treatment.

PMID- 16428696
TI  - Chronic cough due to asthma: ACCP evidence-based clinical practice guidelines.
AB  - BACKGROUND: Asthma is among the most common causes of chronic cough in adult
      nonsmokers. Although cough usually accompanies dyspnea and wheezing, it may
      present in isolation as a precursor of typical asthmatic symptoms, or it may
      remain the predominant or sole symptom of asthma. The latter condition is known
      as cough-variant asthma (CVA). METHODS: Data for this review were obtained from a
      National Library of Medicine (PubMed) search, performed in April 2004, of the
      English language literature from 1975 to 2004, limited to human studies, using
      the search terms "cough" and "asthma." RESULTS: The diagnosis of cough not
      associated with typical asthmatic symptoms (ie, CVA) presents a challenge,
      because physical examination and spirometry findings may be entirely normal.
      Methacholine inhalation challenge testing can demonstrate the presence of
      bronchial hyperresponsiveness; however, the diagnosis of cough due to asthma is
      only confirmed after the resolution of cough with antiasthmatic therapy. In
      general, the therapeutic approach to asthmatic cough is similar to that of the
      typical form of asthma. Most patients will respond to inhaled bronchodilators and
      inhaled corticosteroids. A subgroup of patients will require the addition of
      leukotriene receptor antagonists and/or a short course of oral corticosteroids.
      CONCLUSIONS: Asthma should be considered as a potential etiology in any patient
      with chronic cough, because asthma is a common condition that is commonly
      associated with cough. Because the subgroup of asthmatic patients with CVA
      presents with no other symptoms of asthma, clinical suspicion must remain high.
      Cough due to asthma responds to standard antiasthmatic therapy.

PMID- 16428697
TI  - Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVES: To critically review and summarize the literature on cough and
      gastroesophageal reflux disease (GERD), and to make evidence-based
      recommendations regarding the diagnosis and treatment of chronic cough due to
      GERD. DESIGN/METHODOLOGY: Ovid MEDLINE literature review (through March 2004) for
      all studies published in the English language and selected articles published in
      other languages such as French since 1963 using the medical subject heading terms
      "cough," "gastroesophageal reflux," and "gastroesophageal reflux disease."
      RESULTS: GERD, singly or in combination with other conditions, is one of the most
      common causes of chronic cough. In patients with normal chest radiographic
      findings, GERD most likely causes cough by stimulation of an esophageal-bronchial
      reflex. When GERD causes cough, there may be no GI symptoms up to 75% of the
      time. While 24-h esophageal pH monitoring is the most sensitive and specific test
      in linking GERD and cough in a cause-effect relationship, it has its limitations.
      In addition, there is no general agreement on how to best interpret the test, and
      it cannot detect non-acid reflux events. Therefore, when patients fit the
      clinical profile that has a high likelihood of predicting that GERD is the cause
      of cough, antireflux medical therapy should be empirically instituted. While some
      patients improve with minimal medical therapy, others require more intensive
      regimens. When empiric treatment fails, it cannot be assumed that GERD has been
      ruled out as a cause of chronic cough. Rather, an objective investigation for
      GERD is then recommended because the empiric therapy may not have been intensive
      enough or medical therapy may have failed. Surgery may be efficacious when
      intensive medical therapy has failed in selected patients who have undergone an
      extensive objective GERD evaluation. CONCLUSIONS: Accurately diagnosing and
      successfully treating chronic cough due to GERD can be a major challenge.

PMID- 16428698
TI  - Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice
      guidelines.
AB  - BACKGROUND: The purpose of this review is to present the evidence for the
      diagnosis and treatment of cough due to acute bronchitis and make recommendations
      that will be useful for clinical practice. Acute bronchitis is one of the most
      common diagnoses made by primary care clinicians and emergency department
      physicians. It is an acute respiratory infection with a normal chest radiograph
      that is manifested by cough with or without phlegm production that lasts for up
      to 3 weeks. Respiratory viruses appear to be the most common cause of acute
      bronchitis; however, the organism responsible is rarely identified in clinical
      practice because viral cultures and serologic assays are not routinely performed.
      Fewer than 10% of patients will have a bacterial infection diagnosed as the cause
      of bronchitis. The diagnosis of acute bronchitis should be made only when there
      is no clinical or radiographic evidence of pneumonia, and the common cold, acute
      asthma, or an exacerbation of COPD have been ruled out as the cause of cough.
      Acute bronchitis is a self-limited respiratory disorder, and when the cough
      persists for >3 weeks, other diagnoses must be considered. METHODS:
      Recommendations for this review were obtained from data using a National Library
      of Medicine (PubMed) search dating back to 1950, which was performed in August
      2004. The search was limited to literature published in the English language and
      human studies, using search terms such as "cough," "acute bronchitis," and "acute
      viral respiratory infection." RESULTS: Unfortunately, most previous controlled
      trials guiding the treatment of acute bronchitis have not vigorously
      differentiated acute bronchitis and the common cold, and also have not
      distinguished between an acute exacerbation of chronic bronchitis and acute
      asthma as a cause of acute cough. For patients with the putative diagnosis of
      acute bronchitis, routine treatment with antibiotics is not justified and should
      not be offered. Antitussive agents are occasionally useful and can be offered as
      therapy for short-term symptomatic relief of coughing, but there is no role for
      inhaled bronchodilator or expectorant therapy. Children and adult patients with
      confirmed and probable whooping cough should receive a macrolide antibiotic and
      should be isolated for 5 days from the start of treatment; early treatment within
      the first few weeks will diminish the coughing paroxysms and prevent spread of
      the disease; the patient is unlikely to respond to treatment beyond this period.
      CONCLUSION: Acute bronchitis is an acute respiratory infection that is manifested
      by cough and, at times, sputum production that lasts for no more than 3 weeks.
      This syndrome should be distinguished from the common cold, an acute exacerbation
      of chronic bronchitis, and acute asthma as the cause of acute cough. The
      widespread use of antibiotics for the treatment of acute bronchitis is not
      justified, and vigorous efforts to curtail their use should be encouraged.

PMID- 16428699
TI  - Chronic cough due to chronic bronchitis: ACCP evidence-based clinical practice
      guidelines.
AB  - BACKGROUND: Chronic bronchitis is a disease of the bronchi that is manifested by
      cough and sputum expectoration occurring on most days for at least 3 months of
      the year and for at least 2 consecutive years when other respiratory or cardiac
      causes for the chronic productive cough are excluded. The disease is caused by an
      interaction between noxious inhaled agents (eg, cigarette smoke, industrial
      pollutants, and other environmental pollutants) and host factors (eg, genetic and
      respiratory infections) that results in chronic inflammation in the walls and
      lumen of the airways. As the disease advances, progressive airflow limitation
      occurs, usually in association with pathologic changes of emphysema. This
      condition is called COPD. When a stable patient experiences a sudden clinical
      deterioration with increased sputum volume, sputum purulence, and/or worsening of
      shortness of breath, this is referred to as an acute exacerbation of chronic
      bronchitis as long as conditions other than acute tracheobronchitis are ruled
      out. The purpose of this review is to present the evidence for the diagnosis and
      treatment of cough due to chronic bronchitis, and to make recommendations that
      will be useful for clinical practice. METHODS: Recommendations for this section
      of the review were obtained from data using a National Library of Medicine
      (PubMed) search dating back to 1950, performed in August 2004, of the literature
      published in the English language. The search was limited to human studies, using
      the search terms "cough," "chronic bronchitis," and "COPD." RESULTS: The most
      effective way to reduce or eliminate cough in patients with chronic bronchitis
      and persistent exposure to respiratory irritants, such as personal tobacco use,
      passive smoke exposure, and workplace hazards is avoidance. Therapy with a short
      acting inhaled beta-agonist, inhaled ipratropium bromide, and oral theophylline,
      and a combined regimen of inhaled long-acting beta-agonist and an inhaled
      corticosteroid may improve cough in patients with chronic bronchitis, but there
      is no proven benefit for the use of prophylactic antibiotics, oral
      corticosteroids, expectorants, postural drainage, or chest physiotherapy. For the
      treatment of an acute exacerbation of chronic bronchitis, there is evidence that
      inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe
      cases IV corticosteroids) are useful, but their effects on cough have not been
      systematically evaluated. Therapy with expectorants, postural drainage, chest
      physiotherapy, and theophylline is not recommended. Central cough suppressants
      such as codeine and dextromethorphan are recommended for short-term symptomatic
      relief of coughing. CONCLUSIONS: Chronic bronchitis due to cigarette smoking or
      other exposures to inhaled noxious agents is one of the most common causes of
      chronic cough in the general population. The most effective way to eliminate
      cough is the avoidance of all respiratory irritants. When cough persists despite
      the removal of these inciting agents, there are effective agents to reduce or
      eliminate cough.

PMID- 16428700
TI  - Chronic cough due to nonasthmatic eosinophilic bronchitis: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVES: Nonasthmatic eosinophilic bronchitis is a newly recognized cause of
      chronic cough. Our objective was to review the pathogenesis, natural history,
      diagnosis, and treatment of this condition. METHODS: The current literature was
      reviewed using an Ovid MEDLINE and PubMed literature review for all studies
      published in the English language from 1963 to December 2004 using the medical
      subject heading term "eosinophilic bronchitis." RESULTS: Nonasthmatic
      eosinophilic bronchitis is a common cause of chronic cough. It is characterized
      by the presence of eosinophilic airway inflammation, similar to that seen in
      asthma. However, in contrast to asthma, nonasthmatic eosinophilic bronchitis is
      not associated with variable airflow limitation or airway hyperresponsiveness.
      The differences in functional association are related to differences in the
      localization of mast cells within the airway wall, with airway smooth muscle
      infiltration occurring in patients with asthma, and epithelial infiltration in
      patients with nonasthmatic eosinophilic bronchitis. Diagnosis is made by the
      confirmation of eosinophilic airway inflammation usually with induced sputum
      analysis after the exclusion of other causes for chronic cough on clinical,
      radiologic, and lung function assessment. The cough usually responds well to
      treatment with inhaled corticosteroids. The dose and duration of treatment differ
      between patients. The condition can be transient, episodic, or persistent unless
      treated, and occasionally patients may require long-term prednisone treatment.
      CONCLUSIONS: Further study of this condition may improve our understanding of
      airway inflammation and airway responsiveness, leading to novel targets for
      therapeutic agents for the treatment of both asthma and nonasthmatic eosinophilic
      bronchitis.

PMID- 16428701
TI  - Chronic cough due to bronchiectasis: ACCP evidence-based clinical practice
      guidelines.
AB  - BACKGROUND: Bronchiectasis is a condition that is characterized by the permanent
      dilation of bronchi with destruction of elastic and muscular components of their
      walls, usually due to acute or chronic infection. The cardinal symptom is a
      chronic productive cough. METHODS: Review of articles cited in the systematic
      literature search, along with others found in Ovid MEDLINE and the Cochrane
      Library (including the Cochrane Database of Systematic Reviews, the Cochrane
      Controlled Trial Register, and the Database of Abstracts of Reviews of
      Effectiveness) from 1966 through 2003. RESULTS/CONCLUSIONS: High-resolution CT
      scanning of the chest is the preferred means of establishing the diagnosis of
      bronchiectasis. With the increasing use of antibiotics in the treatment of
      childhood infection in the last several decades, an increasing percentage of
      patients with bronchiectasis now have an underlying disorder that predisposes
      them to chronic or recurrent infection. These include cystic fibrosis, common
      variable immunodeficiency, HIV infection, primary ciliary dyskinesia, allergic
      bronchopulmonary aspergillosis, and chronic Mycobacterium avium complex
      infection. A variety of agents have been used to improve cough effectiveness and
      prevent infectious exacerbations in patients with bronchiectasis, with variable
      results. Chest physiotherapy offers a modest benefit in increasing sputum volume,
      but its long-term effectiveness is unknown. Selected patients with localized
      idiopathic bronchiectasis that causes intolerable symptoms despite maximal
      medical therapy should be offered treatment with surgery. Patients with
      exacerbations of bronchiectasis should be given antibiotics, with the choice of
      agents depending on the likely causative pathogens.

PMID- 16428702
TI  - Chronic cough due to nonbronchiectatic suppurative airway disease
      (bronchiolitis): ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVES: To review the role of nonbronchiectatic suppurative airway disease
      (bronchiolitis) in the spectrum of causes of cough and its management.
      DESIGN/METHODOLOGY: A MEDLINE search (through May 2004) for studies published in
      the English language since 1980 on human subjects using the medical subject
      heading terms "cough," "causes of cough," "etiology of cough," "interstitial lung
      disease," "bronchiolitis," "bronchiolitis obliterans," "diffuse
      panbronchiolitis," and "inflammatory bowel disease" was performed. Case series
      and prospective descriptive clinical trials were selected for review. Any
      references from these studies that were pertinent to the topic were also
      obtained. RESULTS/CONCLUSIONS: In patients with cough in whom other more common
      causes of cough have been excluded, incomplete or irreversible airflow
      limitation, small airways disease seen on high-resolution CT scan, or purulent
      secretions seen on bronchoscopy, should suggest nonbronchiectatic suppurative
      airways disease (bronchiolitis) as a potential primary cause. Successful
      management depends on the identification of the specific underlying disorder.

PMID- 16428703
TI  - Postinfectious cough: ACCP evidence-based clinical practice guidelines.
AB  - BACKGROUND: Patients who complain of a persistent cough lasting >3 weeks after
      experiencing the acute symptoms of an upper respiratory tract infection may have
      a postinfectious cough. Such patients are considered to have a subacute cough
      because the condition lasts for no >8 weeks. The chest radiograph findings are
      normal, thus ruling out pneumonia, and the cough eventually resolves, usually on
      its own. The purpose of this review is to present the evidence for the diagnosis
      and treatment of postinfectious cough, including the most virulent form caused by
      Bordetella pertussis infection, and make recommendations that will be useful for
      clinical practice. METHODS: Recommendations for this section of the guideline
      were obtained from data using a National Library of Medicine (PubMed) search
      dating back to 1950, which was performed in August 2004, of the literature
      published in the English language. The search was limited to human studies, using
      the search terms "cough," "postinfectious cough," "postviral cough," "Bordetella
      pertussis," "pertussis infection," and "whooping cough." RESULTS: The
      pathogenesis of the postinfectious cough is not known, but it is thought to be
      due to the extensive inflammation and disruption of upper and/or lower airway
      epithelial integrity. When postinfectious cough emanates from the lower airway,
      this is often associated with the accumulation of an excessive amount of mucus
      hypersecretion and/or transient airway and cough receptor hyperresponsiveness;
      all may contribute to the subacute cough. In these patients, the optimal
      treatment is not known. Except for bacterial sinusitis or early on in a B
      pertussis infection, therapy with antibiotics has no role, as the cause is not
      bacterial infection. The use of inhaled ipratropium may be helpful. Other causes
      of postinfectious cough are persistent inflammation of the nose and paranasal
      sinuses, which leads to an upper airway cough syndrome (previously referred to as
      postnasal drip syndrome), and gastroesophageal reflux disease, which may be a
      complication of the vigorous coughing. One type of postinfectious cough that is
      particularly virulent is that caused by B pertussis infection. When the cough is
      accompanied by paroxysms of coughing, posttussive vomiting, and/or an inspiratory
      whooping sound, the diagnosis of a B pertussis infection should be made unless
      another diagnosis is proven. This infection is highly contagious but responds to
      antibiotic coverage with an oral macrolide when administered early in the course
      of the disease. A safe and effective vaccine to prevent B pertussis is now
      available for adults as well as children. It is recommended according to CDC
      guidelines. CONCLUSIONS: In patients who have a cough lasting from 3 to 8 weeks
      with normal chest radiograph findings, consider the diagnosis of postinfectious
      cough. In most patients, a specific etiologic agent will not be identified, and
      empiric therapy may be helpful. A high degree of suspicion for cough due to B
      pertussis infection will lead to earlier diagnosis, patient isolation, and
      antibiotic treatment.

PMID- 16428704
TI  - Chronic cough due to lung tumors: ACCP evidence-based clinical practice
      guidelines.
AB  - GOALS/OBJECTIVES: To review the scientific evidence on cough associated with
      tumors in the lungs. METHODS: MEDLINE literature review (through March 2004) for
      all studies published in the English language, including case series and case
      reports, since 1966 using the medical subject heading terms "cough" and "lung
      neoplasms." RESULTS: Primary bronchogenic carcinoma is the most common lethal
      neoplasm in the United States. Malignancies that arise in other organs will often
      metastasize to the lungs. Any form of cancer involving the lungs may be
      associated with cough. However, cough is far more likely to indicate involvement
      of the airways than the lung parenchyma because of the location of cough
      receptors. Cough is present in >65% of patients at the time lung cancer is
      diagnosed, and productive cough is present in >25% of patients. While cough as a
      presenting symptom of lung cancer is common, many studies have shown that lung
      cancer is the cause of chronic cough in <or=2% of all patients who present with a
      chronic cough. CONCLUSIONS: Bronchoscopy is usually indicated when there is
      suspicion of airway involvement by a malignancy. Conversely, bronchoscopy usually
      should not be performed to assess a cough for the possibility of lung cancer when
      there is little risk for lung cancer (nonsmokers) and when there are normal
      findings on a plain chest radiograph. If the lung cancer can be removed
      surgically, cough will usually abate. Radiation therapy, chemotherapy (especially
      with gemcitabine), and endobronchial treatment methods likely will improve cough
      caused by lung cancer. Centrally acting narcotic antitussive agents are usually
      administered for the control of cough caused by lung cancer when other treatment
      methods fail.

PMID- 16428705
TI  - Cough and aspiration of food and liquids due to oral-pharyngeal dysphagia: ACCP
      evidence-based clinical practice guidelines.
AB  - BACKGROUND: Cough may be an indicator of aspiration due to oral-pharyngeal
      dysphagia. METHODS: Relevant literature was identified by searching the
      Communication Sciences and Disorders Dome, the Cumulative Index to Nursing and
      Allied Health Literature, the Educational Resource Information Center, Health &
      Psychosocial Instruments, the American Psychological Association, and the
      National Library of Medicine databases from 1965 to 2004 using the terms
      "deglutition," "aspiration," and "cough." RESULTS: Aspiration was observed on
      radiologic evaluation in over one third of acute stroke patients and in >40% of
      patients undergoing cervical spine surgery. Cough while eating may indicate
      aspiration, but aspiration may be clinically silent. Subjective patient and
      caregiver reports of cough while eating are useful in identifying patients who
      are at risk for aspiration. Objective measures of voluntary cough and tussigenic
      challenges to inhaled irritants are under investigation to determine their
      capacity to predict the risk for aspiration and subsequent pneumonia. The
      treatment of dysphagic patients by a multidisciplinary team, including early
      evaluation by a speech-language pathologist, is associated with improved
      outcomes. Effective clinical interventions such as the use of compensatory
      swallowing strategies and the alteration of food consistencies can be based on
      the results of instrumental swallowing studies. The efficacy of swallowing
      exercises and electrical muscle stimulation is under study. Surgical
      interventions may be considered in selected patients, but studies proving
      efficacy are generally lacking. CONCLUSIONS: Patients who are at risk for
      aspiration can be identified, and appropriate interventions can reduce its
      associated morbidity.

PMID- 16428706
TI  - Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based
      clinical practice guidelines.
AB  - BACKGROUND: A dry, persistent cough is a well-described class effect of the
      angiotensin-converting enzyme (ACE) inhibitor medications. The mechanism of ACE
      inhibitor-induced cough remains unresolved, but likely involves the protussive
      mediators bradykinin and substance P, agents that are degraded by ACE and
      therefore accumulate in the upper respiratory tract or lung when the enzyme is
      inhibited, and prostaglandins, the production of which may be stimulated by
      bradykinin. METHODS: Data for this review were obtained from a National Library
      of Medicine (PubMed) search, which was performed in May 2004, of the literature
      published in the English language from 1985 to 2004, using the search terms
      "angiotensin-converting enzyme," "angiotensin converting enzyme inhibitors," and
      "cough." RESULTS: The incidence of ACE inhibitor-induced cough has been reported
      to be in the range of 5 to 35% among patients treated with these agents. However,
      a much lower incidence has been described in studies of patients presenting for
      the evaluation of chronic cough. The onset of ACE inhibitor-induced cough ranges
      from within hours of the first dose to months after the initiation of therapy.
      Resolution typically occurs within 1 to 4 weeks after the cessation of therapy,
      but cough may linger for up to 3 months. The only uniformly effective treatment
      for ACE inhibitor-induced cough is the cessation of treatment with the offending
      agent. The incidence of cough associated with therapy with angiotensin-receptor
      blockers appears to be similar to that of the control drug. In a minority of
      patients, cough will not recur after the reintroduction of ACE inhibitor therapy.
      CONCLUSIONS: In a patient with chronic cough, ACE inhibitors should be considered
      as wholly or partially causative, regardless of the temporal relation between the
      initiation of ACE inhibitor therapy and the onset of cough. Although the
      cessation of therapy is the only uniformly effective treatment for ACE inhibitor
      induced cough, some pharmacologic agents have been shown to attenuate the cough.

PMID- 16428707
TI  - Habit cough, tic cough, and psychogenic cough in adult and pediatric populations:
      ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVES: To review the literature on habit, tic, and psychogenic cough, and to
      make evidence-based recommendations regarding diagnosis and treatment.
      DESIGN/METHODOLOGY: For data on adults, an Ovid MEDLINE literature review
      (through February 2005) was performed for all studies published in the English
      language, including case series and case reports, since 1966 using the medical
      subject heading terms "habit cough," "psychogenic cough," "tic disorder," "vocal
      tic," "Tourette's syndrome," "honking cough," and "barking cough." For pediatric
      data, articles were identified dating from 1966 from searches of the Cochrane
      Library, PubMed, EMBASE, the list of references in relevant publications, and the
      authors' collection of references with the last search performed in February
      2005. The search terms used were "children" and "vocal tics" or "habit cough," or
      "psychogenic cough" or "chronic cough." RESULTS/CONCLUSIONS: The methodologies
      used and rigor of the diagnostic and therapeutic interventions reported in the
      literature are inconsistent. The putative clinical characteristics of habit cough
      and psychogenic cough, for the most part, have not been prospectively or
      systematically studied. Therefore, on the basis of expert opinion, the diagnoses
      of habit cough or psychogenic cough can be made only after an extensive
      evaluation is performed that includes ruling out tic disorders and uncommon
      causes of chronic cough, and when cough improves with behavior modification or
      psychiatric therapy. In adult patients with chronic cough that remains
      persistently troublesome despite an extensive and thorough evidence-based
      evaluation, and after behavior modification and/or psychiatric therapy have
      failed, unexplained cough should be diagnosed rather than habit cough or
      psychogenic cough. In children, the depth of investigations to rule out uncommon
      causes must be individualized as some investigations and/or treatment may
      increase morbidity. In adult and pediatric patients with chronic cough that is
      associated with troublesome psychological manifestations, psychological
      counseling or psychiatric intervention should be encouraged after other causes
      have been ruled out.

PMID- 16428708
TI  - Chronic cough due to chronic interstitial pulmonary diseases: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVES: To review the role of chronic interstitial pulmonary disease in the
      spectrum of causes of cough and its management. DESIGN/METHODOLOGY: A MEDLINE
      search (through May 2004) for studies published in the English language since
      1980 on human subjects using the medical subject heading terms "cough," "causes
      of cough," "etiology of cough," "interstitial lung disease," "idiopathic
      pulmonary fibrosis," "sarcoidosis," and "hypersensitivity pneumonitis" was
      performed. Case series and prospective descriptive clinical trials were selected
      for review. Any references from these studies that were pertinent to the topic
      were also obtained. RESULTS/CONCLUSIONS: In patients with cough, chronic
      interstitial pulmonary disease should be considered as a primary cause only after
      more common causes, such as upper airway cough syndrome and gastroesophageal
      reflux, have been excluded. Successful management depends on identification of
      the specific disorder.

PMID- 16428709
TI  - Cough: occupational and environmental considerations: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVES: This section of the guideline aims to review the role of occupational
      and environmental factors in causing and contributing to cough. It also aims to
      indicate when such causes should be considered in a clinical setting, and a
      general approach to assessment and management. METHODS: A review was performed of
      published data between 1985 and 2004 using PubMed. The search terms used included
      "air pollution," "sick building syndrome," "occupational asthma," "occupational
      lung disease," "hypersensitivity pneumonitis" (HP), "cigarette smoke," and
      "asthma." Selected articles were chosen when meeting the objectives, but the
      extent of articles available and the limited space for this section does not
      permit a fully comprehensive review of all of these areas, for which the reader
      is referred to other sections of this clinical practice guideline, the published
      literature, textbooks of occupational lung disease, or more specific review
      articles. RESULTS/CONCLUSIONS: Almost any patient presenting with cough may have
      an occupational or environmental cause of or contribution to their cough. The
      importance of this is that recognition and intervention may result in full or
      partial improvement of the cough, may limit the need for medication/symptomatic
      treatment, and may improve the long-term prognosis. Nonoccupational environmental
      contributing factors for upper and lower airway causes of cough include indoor
      irritant and allergenic agents such as cigarette smoke, cooking fumes, animals,
      dust mites, fungi, and cockroaches. Causes of HP indoors include birds and fungal
      antigens. Outdoor pollutants and allergens also contribute to upper and lower
      airway causes of cough. Occupational exposures can cause hypersensitivity
      responses leading to rhinitis and upper airway cough syndrome, previously
      referred to as postnasal drip syndrome, as well as asthma, HP, chronic beryllium
      disease, and hard metal disease, as well as irritant or toxic responses. The
      diagnosis is only reached by initially considering possible occupational and
      environmental factors, and by obtaining an appropriate medical history to
      determine relevant exposures, followed by objective investigations. This may
      require referral to a center of expertise.

PMID- 16428710
TI  - Chronic cough due to tuberculosis and other infections: ACCP evidence-based
      clinical practice guidelines.
AB  - BACKGROUND: Although tuberculosis (TB) and other lung infections are common
      throughout the developing world, they are not among the most common causes of
      chronic cough. METHODS: Articles were selected from a MEDLINE search from 1966
      through 2003 (using medical subject heading words "cough," "tuberculosis," and
      "lung infection"), and World Health Organization and Centers for Disease Control
      and Prevention web sites. RESULTS: Because of the contagious nature of TB and its
      potential for devastating morbidity and mortality for individual patients and
      society, TB should be considered early on in the workup of patients with chronic
      cough when the likelihood of active TB is high. On a worldwide basis, many cases
      of chronic cough are caused by infection including TB, and endemic fungi and
      parasites are important causes of cough in specific geographic regions. The
      convergence of the AIDS epidemic with the high prevalence of TB in the developing
      world has fueled the marked increase in cases of TB. Persons who live and work in
      facilities like prisons and nursing homes are also susceptible to tuberculous
      infection, and they spread it to others. Infection with endemic fungi and
      parasites should be considered in patients with chronic cough who live, or have
      lived, in these areas. CONCLUSION: Patients with unexplained chronic cough who
      have resided in areas having endemic infection with TB, fungi, or parasites
      should undergo diagnostic evaluation for these pathogens when more common causes
      of cough have been ruled out.

PMID- 16428711
TI  - Peritoneal dialysis and cough: ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVE: To review the clinical associations between peritoneal dialysis (PD)
      and cough. METHODOLOGY: A literature review was performed on PubMed for articles
      published between 1983 and 2004 using the search terms "dialysis" and "cough."
      RESULTS/CONCLUSIONS: Patients receiving PD are more likely to develop a cough
      than other patients with end-stage renal disease who are receiving hemodialysis.
      Although both groups of patients frequently receive medications, such as
      angiotensin-converting enzyme inhibitors and beta-adrenergic blocking agents,
      that can trigger cough and both may be at increased risk for fluid overload and
      pulmonary edema, the increased risk associated with PD appears to relate to
      gastroesophageal reflux, likely from the peritoneal dialysate.

PMID- 16428712
TI  - Cough in the immunocompromised host: ACCP evidence-based clinical practice
      guidelines.
AB  - BACKGROUND: Patients with compromised immune systems often complain of chronic
      cough. While these patients are susceptible to opportunistic infections that
      should be considered in the evaluation, common causes should also be
      investigated. METHODS: MEDLINE search using the terms "cough,"
      "immunocompromise," "HIV," "AIDS," "neutropenia," and "corticosteroids," from
      1966 through the end of 2003. RESULTS: Patients with compromised immune systems
      and chronic cough usually have the same disorders causing cough as in the general
      population. However, depending on the nature and severity of the immune defect,
      they may also have a variety of infections not usually encountered in
      immunocompetent hosts. CONCLUSION: In immunocompromised patients presenting with
      cough, the initial diagnostic evaluation should be the same as that for healthy
      hosts. However, when these diagnoses have been excluded, opportunistic infections
      should be considered.

PMID- 16428713
TI  - Uncommon causes of cough: ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVES: To describe the uncommon causes of cough. DESIGN/METHODOLOGY: An
      English language literature search by MEDLINE citations from 1975 through 2004
      was used to identify publications on uncommon pulmonary and nonpulmonary
      disorders in which cough was present as the major or presenting symptom in >50%
      of those persons affected by the uncommon diseases. RESULTS: A substantial number
      of uncommon or rare pulmonary and nonpulmonary disorders were identified. The
      uncommon occurrence of these diseases made it difficult to develop a meaningful
      evidence-based guideline to the diagnosis and therapy of many of the uncommon
      causes of cough. As cough was the major or presenting symptom, it was usually
      initially attributed to common respiratory diseases (eg, asthma or bronchitis).
      As a result, a substantial time lag existed from the onset of cough to the
      diagnosis of the etiologic entity. Diagnostic tests limited to the respiratory
      system did not always provide clues to the diagnosis of uncommon causes of cough.
      CONCLUSIONS: Cough is the major or presenting symptom in many uncommon pulmonary
      and nonpulmonary disorders. A strong index of suspicion is essential to consider
      and diagnose the uncommon causes of cough. The diagnosis and management of cough
      in patients with uncommon causes of cough is dependent on the underlying
      etiology.

PMID- 16428714
TI  - Unexplained (idiopathic) cough: ACCP evidence-based clinical practice guidelines.
AB  - OBJECTIVE: To review the literature on unexplained cough, previously referred to
      as idiopathic cough. METHODS: Search of MEDLINE (through May 2004) for studies
      published in the English language since 1980 on human subjects using the medical
      subject heading terms "cough," "unexplained cough," and "idiopathic cough." We
      selected case series and prospective descriptive clinical trials. We also
      obtained any references from these studies that were pertinent to the topic.
      RESULTS: The diagnosis of unexplained (idiopathic) cough should only be
      considered after a thorough diagnostic and treatment approach for the most common
      causes of cough has been completed and uncommon causes have been adequately
      evaluated Unless this is done, it is likely that many patients with a definable
      cause of cough will be misdiagnosed as having "unexplained cough." CONCLUSION:
      The diagnosis of unexplained cough is probably made too often based on an
      inadequate diagnostic workup or treatment course to determine the specific cause
      of cough. Nevertheless, there may be a group of patients in whom none of the
      usual explanations for cough may be present. For this group, the committee
      unanimously recommends using the diagnostic term unexplained cough, rather than
      idiopathic cough.

PMID- 16428715
TI  - An empiric integrative approach to the management of cough: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVE: Review the literature to provide a comprehensive approach, including
      algorithms for the clinician to follow in evaluating and treating the patient
      with acute, subacute, and chronic cough. METHODS: We searched MEDLINE (through
      May 2004) for studies published in the English language since 1980 on human
      subjects using the medical subject heading terms "cough," "treatment of cough,"
      and "empiric treatment of cough." We selected case series and prospective
      descriptive clinical trials. We also obtained any references from these studies
      that were pertinent to the topic. RESULTS: The relative frequency of the
      disorders (alone and in combination) that can cause cough as well as the
      sensitivity and specificity of many but not all diagnostic tests in predicting
      the cause of cough are known. An effective approach to successfully manage
      chronic cough is to sequentially evaluate and treat for the common causes of
      cough using a combination of selected diagnostic tests and empiric therapy.
      Sequential and additive therapy is often crucial because more than one cause of
      cough is frequently present. CONCLUSION: Algorithms that provide a "road map"
      that the clinician can follow are useful and are presented for acute, subacute,
      and chronic cough.

PMID- 16428716
TI  - Assessing cough severity and efficacy of therapy in clinical research: ACCP
      evidence-based clinical practice guidelines.
AB  - OBJECTIVES: To review the literature on identifying cough and to make evidence
      based recommendations for assessing the efficacy of cough-modifying agents in
      clinical research. DESIGN/METHODOLOGY: Ovid MEDLINE literature review (through
      March 2004) for all studies published in the English language since 1953 using
      the medical subject heading terms "assessing the impact of cough," "assessing the
      efficacy of cough treatments," "tussigenic challenges," "cough counting,"
      "character and timing of cough," "visual analog scales," "cough scoring systems,"
      "health related quality of life instruments," "cough-specific health-related
      quality of life instruments," "citric acid challenge," "capsaicin challenge,"
      "flow-volume loops," "assessing airway inflammation," "lipid laden macrophages in
      sputum," and "exhaled nitric oxide." RESULTS/CONCLUSIONS: To optimally evaluate
      the efficacy of cough-modifying agents, investigators should use both subjective
      and objective methods, because they have the potential to measure different
      things. A patient's subjective response is likely the only one that measures the
      impact of the intensity of cough. With respect to subjective methods, it is
      recommended that a cough-specific health-related quality-of-life instrument be
      utilized because valid and reliable instruments exist. Even though visual analog
      scales have not been psychometrically tested, they are recommended because they
      are commonly used and valid, and they are likely to yield different but
      complementary results. Because there are cough-specific health-related quality-of
      life instruments that have been fully psychometrically tested, and the same
      cannot be said for visual analog scales, this is a reason to use cough-specific
      health-related quality-of-life instruments as the primary, subjective outcome
      measure of choice. With respect to objective methods, tussigenic challenges can
      be used before and after the intervention to assess the effect of therapy on
      cough sensitivity. They are most likely to be helpful in disease states in which
      cough reflex sensitivity is known to be heightened. Because the act of coughing
      has the potential to traumatize the upper airway (eg, vocal cords), assessing the
      presence of upper airway edema before and after therapy with flow-volume loops
      may be useful. Investigators must be cautious and not assume that observing
      changes suggestive of inflammation and edema of upper airway structures is
      specific for any particular disease. Cough counting is recommended with a
      computerized methodology that is reliable and accurate, noninvasive and portable,
      and easy to use in unattended, ambulatory real-life settings within a subject's
      home environment when it can be done over a 24-h period of time.

PMID- 16428718
TI  - Nonpharmacologic airway clearance therapies: ACCP evidence-based clinical
      practice guidelines.
AB  - BACKGROUND: Airway clearance may be impaired in disorders associated with
      abnormal cough mechanics, altered mucus rheology, altered mucociliary clearance,
      or structural airway defects. A variety of interventions are used to enhance
      airway clearance with the goal of improving lung mechanics and gas exchange, and
      preventing atelectasis and infection. METHOD: A formal systematic review of
      nonpharmacologic protussive therapies was performed and constitutes the basis for
      this section of the guideline. In addition, the articles reviewed were found
      using the same methodology but were not limited to those that focused only on
      cough as a symptom. The MEDLINE database was searched for this review and
      consisted of studies published in the English language between 1960 and April
      2004. The search terms used were "chest physiotherapy," "forced expiratory
      technique," "positive expiratory pressure," "high frequency chest compression,"
      "insufflation," and "exsufflation." RESULTS: In general, studies of
      nonpharmacologic methods of improving cough clearance are limited by
      methodological constraints, and most were conducted only in patients with cystic
      fibrosis. Chest physiotherapy, including postural drainage, chest wall percussion
      and vibration, and a forced expiration technique (called huffing), increase
      airway clearance as assessed by sputum characteristics (ie, volume, weight, and
      viscosity) and clearance of the radioaerosol from the lung, but the long-term
      efficacy of these techniques compared with unassisted cough alone is unknown.
      Other devices that allow patients to achieve the same benefits derived from chest
      physiotherapy without the assistance of a caregiver appear to be as effective as
      chest physiotherapy in increasing sputum production. CONCLUSIONS: Some
      nonpharmacologic therapies are effective in increasing sputum production, but
      their long-term efficacy in improving outcomes compared with unassisted cough
      alone is unknown.

PMID- 16428719
TI  - Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVES: To review relevant literature and present evidence-based guidelines
      to assist general and specialist medical practitioners in the evaluation and
      management of children who present with chronic cough. METHODOLOGY: The Cochrane,
      MEDLINE, and EMBASE databases, review articles, and reference lists of relevant
      articles were searched and reviewed by a single author. The date of the last
      comprehensive search was December 5, 2003, and that of the Cochrane database was
      November 7, 2004. The authors' own databases and expertise identified additional
      articles. RESULTS/CONCLUSIONS: Pediatric chronic cough (ie, cough in children
      aged <15 years) is defined as a daily cough lasting for >4 weeks. This time frame
      was chosen based on the natural history of URTIs in children and differs from the
      definition of chronic cough in adults. In this guideline, only chronic cough will
      be discussed. Chronic cough is subdivided into specific cough (ie, cough
      associated with other symptoms and signs suggestive of an associated or
      underlying problem) and nonspecific cough (ie, dry cough in the absence of an
      identifiable respiratory disease of known etiology). The majority of this section
      focuses on nonspecific cough, as specific cough encompasses the entire spectrum
      of pediatric pulmonology. A review of the literature revealed few randomized
      controlled trials for treatment of nonspecific cough. Management guidelines are
      summarized in two pathways. Recommendations are derived from a systematic review
      of the literature and were integrated with expert opinion. They are a general
      guideline only, do not substitute for sound clinical judgment, and are not
      intended to be used as a protocol for the management of all children with a
      coughing illness. Children (aged <15 years) with cough should be managed
      according to child-specific guidelines, which differ from those for adults as the
      etiologic factors and treatments for children are sometimes different from those
      for adults. Cough in children should be treated based on etiology, and there is
      no evidence for using medications for the symptomatic relief of cough. If
      medications are used, it is imperative that the children are followed up and
      therapy with the medications stopped if there is no effect on the cough within an
      expected time frame. An evaluation of the time to response is important.
      Irrespective of diagnosis, environmental influences and parental expectations
      should be discussed and managed accordingly. Cough often impacts the quality of
      life of both children and parents, and the exploration of parental expectations
      and fears is often valuable in the management of cough in children.

PMID- 16428720
TI  - Potential future therapies for the management of cough: ACCP evidence-based
      clinical practice guidelines.
AB  - BACKGROUND: When the etiology of a patient's chronic cough is established,
      specific antitussive therapy that is aimed at a particular cause of cough is
      highly effective. Nevertheless, in certain situations, therapy with cough
      suppressants, which previously were classified as nonspecific antitussive
      therapy, and which aim at suppressing the cough reflex regardless of the cause of
      cough, will be necessary. METHODOLOGY: The data for this review were obtained
      with the aid of a National Library of Medicine (PubMed) search, which was
      performed in June 2004, of literature published in the English language from 1966
      to 2004, using the search terms "cough," "antitussive," "pharmacotherapy,"
      "future therapies, " and "potential therapies." RESULTS/CONCLUSIONS: Currently
      available cough-suppressant therapy is severely limited by a dearth of effective
      agents and/or their unacceptable side effects. Several classes of pharmacologic
      agents are currently under investigation in an attempt to develop clinically
      useful cough suppressants.

PMID- 16428717
TI  - Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based
      clinical practice guidelines.
AB  - BACKGROUND: Cough-suppressant therapy, previously termed nonspecific antitussive
      therapy, incorporates the use of pharmacologic agents with mucolytic effects
      and/or inhibitory effects on the cough reflex itself. The intent of this type of
      therapy is to reduce the frequency and/or intensity of coughing on a short-term
      basis. METHODS: Data for this review were obtained from several National Library
      of Medicine (PubMed) searches (from 1960 to 2004), which were performed between
      May and September 2004, of the literature published in the English language,
      limited to human studies, using combinations of the search terms "cough," "double
      blind placebo-controlled," "antitussive," "mucolytic," "cough clearance," "common
      cold," "protussive," "guaifenesin," "glycerol," and "zinc." RESULTS: Mucolytic
      agents are not consistently effective in ameliorating cough in patients with
      bronchitis, although they may be of benefit to this population in other ways.
      Peripheral and central antitussive agents can be useful in patients with chronic
      bronchitis, but can have little efficacy in patients with cough due to upper
      respiratory infection. Some protussive agents are effective in increasing cough
      clearance, but their long-term effectiveness has not been established. DNase is
      not effective as a protussive agent in patients with cystic fibrosis. Inhaled
      mannitol is acutely effective in this patient population, but its therapeutic
      potential must be investigated further. CONCLUSIONS: These findings suggest that
      suppressant therapy is most effective when used for the short-term reduction of
      coughing. Relatively few drugs are effective as cough suppressants.

PMID- 16428721
TI  - Future directions in the clinical management of cough: ACCP evidence-based
      clinical practice guidelines.
AB  - OBJECTIVES: To impart a call for further research into the identified domains of
      particular interest in the etiology, management, and treatment of cough.
      DESIGN/METHODOLOGY: A literature review was performed using the search term
      "cough" in PubMed between 1983 and 2004. The final draft of this guideline was
      reviewed, in addition to recent studies on cough, and suggestions provided by the
      authors were collated into a definitive inventory of specific areas in which the
      lack of quality evidence encumbered the development of clinically relevant
      evidence-based recommendations. RESULTS/CONCLUSIONS: Although our understanding
      of the causes and optimal management of chronic cough have significantly
      increased over the past 25 years, further research remains to be done on this
      common symptom. This is reflected by the generally low level of evidence for many
      of the recommendations in these guidelines. Research is particularly needed on
      the optimal treatment of postinfectious cough, how to distinguish acute
      bronchitis from other conditions, how to reliably diagnose and treat cough due to
      gastroesophageal reflux disease, clearly identifying a role for nonpharmacologic
      protussive treatment modalities in diseases associated with an increased
      production of bronchial secretions, determining how often cough in patients with
      interstitial lung disease is due to conditions other than these, establishing the
      spectrum and frequency of causes of chronic cough in the immunocompromised hosts,
      and better characterizing psychogenic cough. Further studies are also needed on
      methods for the assessment of cough, in particular, noninvasive measures of
      airway inflammation, and pharmacotherapy. It should be determined how often
      unexplained cough (previously referred to as idiopathic cough) is due to the use
      of non-evidence-based guidelines or to environmental causes, and assessed whether
      an empiric, integrative approach of diagnosing chronic cough leads to better
      outcomes, including cost-effectiveness, than routine testing. While much work has
      been done on chronic cough, we need studies on the spectrum and frequency of
      acute and subacute coughs.

PMID- 16428724
TI  - Multifunctional role of choline binding protein G in pneumococcal pathogenesis.
AB  - Members of the choline binding protein (Cbp) family are noncovalently bound to
      phosphorylcholine residues on the surface of Streptococcus pneumoniae. It has
      been suggested that CbpG plays a role in adherence and increase virulence both at
      the mucosal surface and in the bloodstream, but the function of this protein has
      been unclear. A new sequence analysis indicated that CbpG is a possible member of
      the S1 family of multifunctional surface-associated serine proteases. Clinical
      isolates contained two alleles of cbpG, and one-third of the strains expressed a
      truncated protein lacking the C-terminal, cell wall-anchoring choline binding
      domain. CbpG on the surface of pneumococci (full length) or released into the
      supernatant (truncated) showed proteolytic activity for fibronectin and casein,
      as did CbpG expressed on lactobacilli or as a purified full-length or truncated
      recombinant protein. Recombinant CbpG (rCbpG)-coated beads adhered to eukaryotic
      cells, and TIGR4 mutants lacking CbpG or having a truncated CbpG protein showed
      decreased adherence in vitro and attenuation of disease in mouse challenge models
      of colonization, pneumonia, and bacteremia. Immunization with rCbpG was
      protective in an animal model of colonization and sepsis. We propose that CbpG is
      a multifunctional surface protein that in the cell-attached or secreted form
      cleaves host extracellular matrix and in the cell-attached form participates in
      bacterial adherence. This is the first example of distinct functions in virulence
      that are dependent on natural variation in expression of a choline binding
      domain.

PMID- 16428722
TI  - Do CD1-restricted T cells contribute to antibody-mediated immunity against
      Mycobacterium tuberculosis?

PMID- 16428723
TI  - Analysis of the function of enteropathogenic Escherichia coli EspB by random
      mutagenesis.
AB  - Enteropathogenic Escherichia coli (EPEC) is an important cause of infantile
      diarrhea, especially in developing countries. EspB, a key virulence factor of
      EPEC, is required for the attaching and effacing effect characteristic of EPEC
      and enterohemorrhagic E. coli and has been posited to play several functions in
      the process of infection. Attaching and effacing activity is associated with the
      accumulation of filamentous actin beneath adherent bacteria as measured in the
      fluorescence actin staining (FAS) test. To determine whether different domains of
      EspB are responsible for different functions, 42 plasmids carrying mutated espB
      were introduced into an espB deletion mutant. Two major groups of espB mutants
      were identified. One group of 17 mutants exhibited positive FAS results and
      normal levels of hemolytic activity. Another group of 22 mutants exhibited
      negative FAS results and low levels of hemolytic activity. Three mutants were
      exceptional. One mutant was FAS positive but had significantly reduced hemolytic
      activity. Conversely, a second mutant was FAS negative but had full hemolytic
      activity. A third mutant had a significantly reduced FAS level compared to the
      wild type but full hemolytic activity. The results of EspF and Tir translocation
      assays confirmed that FAS-negative insertions disrupt effector translocation and
      mutants with FAS-positive insertions retain protein translocation activity. These
      results suggest that EspB has distinct domain functions involved in effector
      translocation that can be distinguished from its role as a component of the
      translocation pore.

PMID- 16428725
TI  - Nontypeable Haemophilus influenzae adheres to intercellular adhesion molecule 1
      (ICAM-1) on respiratory epithelial cells and upregulates ICAM-1 expression.
AB  - Nontypeable Haemophilus influenzae (NTHI) is an important respiratory pathogen.
      NTHI initiates infection by adhering to the airway epithelium. Here, we report
      that NTHI interacts with intracellular adhesion molecule 1 (ICAM-1) expressed by
      respiratory epithelial cells. A fourfold-higher number of NTHI bacteria adhered
      to Chinese hamster ovary (CHO) cells transfected with human ICAM-1 (CHO-ICAM-1)
      than to control CHO cells (P < or = 0.005). Blocking cell surface ICAM-1 with
      specific antibody reduced the adhesion of NTHI to A549 respiratory epithelial
      cells by 37% (P = 0.001) and to CHO-ICAM-1 cells by 69% (P = 0.005).
      Preincubating the bacteria with recombinant ICAM-1 reduced adhesion by 69% (P =
      0.003). The adherence to CHO-ICAM-1 cells of NTHI strains deficient in the
      adhesins P5, P2, HMW1/2, and Hap or expressing a truncated lipooligosaccharide
      was compared to that of parental strains. Only strain 1128f-, which lacks the
      outer membrane protein (OMP) P5-homologous adhesin (P5 fimbriae), adhered less
      well than its parental strain. The numbers of NTHI cells adhering to CHO-ICAM-1
      cells were reduced by 67% (P = 0.009) following preincubation with anti-P5
      antisera. Furthermore, recombinant ICAM bound to an OMP preparation from strain
      1128f+, which expresses P5, but not to that from its P5-deficient mutant,
      confirming a specific interaction between ICAM-1 and P5 fimbriae. Incubation of
      respiratory epithelial cells with NTHI increased ICAM-1 expression fourfold
      (P=0.001). Adhesion of NTHI to the respiratory epithelium, therefore, upregulates
      the expression of its own receptor. Blocking interactions between NTHI P5
      fimbriae and ICAM-1 may reduce respiratory colonization by NTHI and limit the
      frequency and severity of NTHI infection.

PMID- 16428726
TI  - Characterization of enteropathogenic Escherichia coli mutants that fail to
      disrupt host cell spreading and attachment to substratum.
AB  - Upon infection of host cells, enteropathogenic Escherichia coli (EPEC) delivers a
      set of effector proteins into the host cell cytoplasm via the type III secretion
      system (TTSS). The effectors subvert various host cell functions. We found that
      EPEC interferes with the spreading and ultimately with the attachment of
      suspended fibroblasts or epithelial cells, and we isolated mini-Tn10kan insertion
      mutants that failed to similarly affect host cells. In most mutants, the
      insertion sites were mapped to genes encoding TTSS components, including cesD,
      escC, escJ, escV, espD, sepL, espB, and escF. Other mutants contained insertions
      in micC or upstream of bfpP, yehL, or ydeP. The insertion upstream of ydeP was
      associated with a reduction in TTSS protein production and was studied further.
      To determine whether the apparent repression was due to constitutive expression
      of the downstream encoded genes, ydeP and ydeO expression vectors were
      constructed. Expression of recombinant YdeP, YdeO, or EvgA, a positive regulator
      of both ydeP and ydeO, repressed TTSS protein production. Our results suggest
      that upon activation of the EvgAS two-component system, EvgA (the response
      regulator) activates both ydeP and ydeO expression and that YdeP and YdeO act
      conjointly, directly or indirectly repressing expression of the TTSS genes.

PMID- 16428727
TI  - Phospholipase A2 functions in Pseudomonas aeruginosa-induced apoptosis.
AB  - Pseudomonas aeruginosa, a gram-negative, facultative pathogen, causes severe and
      often even lethal infections in immunocompromised patients, as well as cystic
      fibrosis patients. We show here that a variety of P. aeruginosa strains activate
      phospholipase A2 (PLA2), cultured epithelial cells, and fibroblasts, resulting in
      increased intracellular and extracellular arachidonic acid release. The use of
      different PLA2 inhibitors revealed that P. aeruginosa-induced arachidonic acid
      release is mediated by activation of cytosolic PLA2 (cPLA2), whereas iPLA2 or
      sPLA2 do not seem to be involved in the response to P. aeruginosa. Likewise, the
      cPLA2-specific inhibitors MAFP and AACOCF3 prevented apoptosis of cultured
      epithelial cells upon P. aeruginosa infection, whereas inhibitors specific for
      iPLA2 or sPLA2 were without effect. The physiological significance of these
      findings is indicated by an inhibition of apoptosis in tracheal epithelial cells
      upon in vivo infection with P. aeruginosa. The data indicate that arachidonic
      acid generation by activation of cPLA2 during P. aeruginosa infection plays an
      important role in the induction of host cell death.

PMID- 16428728
TI  - Deletion of the Mycobacterium tuberculosis alpha-crystallin-like hspX gene causes
      increased bacterial growth in vivo.
AB  - Hypervirulent mutants of Mycobacterium tuberculosis, whose growth rates are
      higher in vivo, have now been reported to have mutations in both regulatory and
      structural genes, but the basis for this unusual phenotype is not understood. One
      hypervirulence gene, dosR (devR, Rv2031c), activates transcription of
      approximately 50 genes in this pathogen in response to hypoxia and nitric oxide
      stress. The most dramatic activation (approximately 80-fold) is activation of the
      hspX (acr, Rv2031c) gene, which encodes a 16-kDa alpha-crystallin-like protein
      that is a major antigen. In this study we found that a Deltaacr mutant exhibited
      increased growth following infection of BALB/c mice in vivo and in both resting
      and activated macrophages in vitro (as measured by the number of CFU). The
      increased growth in macrophages was equal to that of a DeltadosR mutant, while
      introduction of a constitutively expressed hspX gene reduced the DeltadosR
      virulence to wild-type levels. These results suggest that the increased number of
      CFU of the DeltadosR mutant was largely due to loss of hspX expression. We also
      confirmed that constitutive expression of hspX slows growth in vitro, and we
      propose that hspX plays an active role in slowing the growth of M. tuberculosis
      in vivo immediately following infection.

PMID- 16428729
TI  - Importance of heat-labile enterotoxin in colonization of the adult mouse small
      intestine by human enterotoxigenic Escherichia coli strains.
AB  - Enterotoxigenic Escherichia coli (ETEC) infections are a significant cause of
      diarrheal disease and infant mortality in developing countries. Studies of ETEC
      pathogenesis relevant to vaccine development have been greatly hampered by the
      lack of a suitable small-animal model of infection with human ETEC strains. Here,
      we demonstrate that adult immunocompetent outbred mice can be effectively
      colonized with the prototypical human ETEC H10407 strain (colonization factor
      antigen I; heat-labile and heat-stable enterotoxin positive) and that production
      of heat-labile holotoxin provides a significant advantage in colonization of the
      small intestine in this model.

PMID- 16428730
TI  - Sigma B contributes to Listeria monocytogenes gastrointestinal infection but not
      to systemic spread in the guinea pig infection model.
AB  - Contributions of the alternative sigma factor sigmaB to Listeria monocytogenes
      infection were investigated using strains bearing null mutations in sigB, prfA,
      or inlA or in selected inlA or prfA promoter regions. The DeltaP4inlA strain,
      which has a deletion in the sigmaB-dependent P4inlA promoter, and the DeltasigB
      strain had significantly reduced invasion efficiencies relative to that of the
      wild-type strain in the Caco-2 human colorectal epithelial cell line, while the
      invasion efficiency of a strain bearing a deletion in the partially sigmaB
      dependent P2prfA promoter region did not differ from that of the wild type. The
      virulence of the DeltasigB and DeltaP4inlA strains was attenuated in
      intragastrically inoculated guinea pigs, with the DeltasigB strain showing
      greater attenuation, while the virulence capacity of the DeltaP2prfA strain was
      similar to that of the wild-type strain, suggesting that attenuation of virulence
      due to the DeltasigB mutation does not result from loss of sigmaB-dependent prfA
      transcription. Our results show that sigmaB-dependent activation of inlA is
      important for cell invasion and gastrointestinal infection and suggest that
      sigmaB-regulated genes in addition to inlA appear to contribute to
      gastrointestinal infection. Interestingly, the virulence of the DeltasigB strain
      was not attenuated in intravenously infected guinea pigs. We conclude that (i) L.
      monocytogenes sigmaB plays a critical role in invasion of human host cells, (ii)
      sigmaB-mediated contributions to invasion are, in part, due to direct effects on
      inlA transcription but not on prfA transcription, and (iii) sigmaB plays a
      critical role during the gastrointestinal stage of listeriosis in the guinea pig
      but is not important for systemic spread of the organism.

PMID- 16428731
TI  - Toll-like receptor 4 protects against lethal Leptospira interrogans serovar
      icterohaemorrhagiae infection and contributes to in vivo control of leptospiral
      burden.
AB  - The roles of innate immune responses in protection from or pathogenesis of severe
      leptospirosis remain unclear. We examined the role of Toll-like receptors (TLRs)
      in mouse infection and macrophage responses to Leptospira. C3H/HeJ mice (TLR4
      deficient) and C3H/HeJ-SCID mice, but not C3H/OuJ mice (TLR4 intact), died after
      intraperitoneal infection with Leptospira interrogans serovar
      Icterohaemorrhagiae. Death in both C3H/HeJ mouse strains was associated with
      jaundice and pulmonary hemorrhage, similar to the patient from whom the isolate
      was obtained. In chronic sublethal infection, TLR4-deficient mice harbored more
      leptospires in liver, lung, and kidney than control mice. Heat-killed Leptospira
      stimulated macrophages to secrete proinflammatory cytokines, tumor necrosis
      factor alpha, interleukin-6, and macrophage inflammatory protein 2 not inhibited
      by polymyxin B, suggesting that leptospiral lipopolysaccharide (LPS) did not
      drive these responses. Anti-TLR4 and anti-MD-2 but not anti-CD14 monoclonal
      antibodies inhibited cytokine production. Peritoneal macrophages from CD14-/- and
      TLR2-/- mice exhibited no defect in cytokine responses to Leptospira compared to
      controls. Macrophages from C3H/HeJ, TLR4-/-, and MyD88-/- mice secreted far-lower
      levels of cytokines than wild-type macrophages in response to Leptospira. TLR4
      plays a crucial role in protection from acute lethal infection and control of
      leptospiral burden during sublethal chronic infection. Cytokine responses in
      macrophages correlated with leptospiral clearance. These TLR4-dependent but
      CD14/TLR2-independent responses are likely mediated by a leptospiral ligand(s)
      other than LPS.

PMID- 16428732
TI  - Phenotypic switching in a Cryptococcus neoformans variety gattii strain is
      associated with changes in virulence and promotes dissemination to the central
      nervous system.
AB  - This is the first report of a Cryptococcus neoformans var. gattii strain
      (serotype B) that switches reversibly between its parent mucoid (NP1-MC) colony
      morphology and a smooth (NP1-SM) colony morphology. Similar to C. neoformans var.
      grubii and C. neoformans var. neoformans strains, the switch is associated with
      changes in the polysaccharide capsule and virulence in animal models. In murine
      infection models, NP1-MC is significantly more virulent than NP1-SM (P < 0.021).
      In contrast to the serotype A and D strains, the serotype B strain switches in
      vivo reversibly between both colony morphologies. The polysaccharide of NP1-MC
      exhibits a thicker capsule, and thus NP1-MC exhibits enhanced intracellular
      survival in macrophages. Consistent with this finding, switching to the mucoid
      variant is observed in pulmonary infection with NP1-SM. In contrast, the thin
      polysaccharide capsule of NP1-SM permits better crossing of the blood-brain
      barrier. In this regard, only smooth colonies were grown from brain homogenates
      of NP1-MC-infected mice. Our findings have important implications for the
      pathogenesis of cryptococcosis and suggest that phenotypic switching affects host
      pathogen interactions in the local microenvironment. This altered interaction
      then selects for specific colony variants to arise in a pathogen population.

PMID- 16428733
TI  - Entamoeba histolytica infection in children and protection from subsequent
      amebiasis.
AB  - The contribution of amebiasis to the burden of diarrheal disease in children and
      the degree to which immunity is acquired from natural infection were assessed in
      a 4-year prospective observational study of 289 preschool children in an urban
      slum in Dhaka, Bangladesh. Entamoeba histolytica infection was detected at least
      once in 80%, and repeat infection in 53%, of the children who completed 4 years
      of observation. Annually there were 0.09 episodes/child of E. histolytica
      associated diarrhea and 0.03 episodes/child of E. histolytica-associated
      dysentery. Fecal immunoglobulin A (IgA) anti-parasite Gal/GalNAc lectin
      carbohydrate recognition domain (anti-CRD) was detected in 91% (183/202) of the
      children at least once and was associated with a lower incidence of infection and
      disease. We concluded that amebiasis was a substantial burden on the overall
      health of the cohort children. Protection from amebiasis was associated with a
      stool anti-CRD IgA response. The challenge of producing an effective vaccine will
      be to improve upon naturally acquired immunity, which does not provide absolute
      protection from reinfection.

PMID- 16428734
TI  - N-acylhomoserine lactones antagonize virulence gene expression and quorum sensing
      in Staphylococcus aureus.
AB  - Many gram-negative bacteria employ N-acylhomoserine lactone (AHL)-mediated quorum
      sensing to control virulence. To determine whether gram-positive bacteria such as
      Staphylococcus aureus respond to AHLs, we used a growth-dependent lux reporter
      fusion. Exposure of S. aureus to different AHLs revealed that 3-oxo-substituted
      AHLs with C10 to C14 acyl chains inhibited light output and growth in a
      concentration-dependent manner, while short-chain AHLs had no effect. N-(3
      Oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) inhibited the production of
      exotoxins and cell wall fibronectin-binding proteins but enhanced protein A
      expression. Since these processes are reciprocally regulated via the S. aureus
      agr quorum-sensing system, which in turn, is regulated via sar, we examined the
      effect of AHLs on sarA and agr. At sub-growth-inhibitory concentrations of 3-oxo
      C12-HSL, both sarA expression and agr expression were inhibited, indicating that
      the action of 3-oxo-C12-HSL is mediated at least in part through antagonism of
      quorum sensing in S. aureus. Spent culture supernatants from Pseudomonas
      aeruginosa, which produces both 3-oxo-C12-HSL and N-butanoyl-homoserine lactone
      (C4-HSL), also inhibited agr expression, although C4-HSL itself was inactive in
      this assay. Since quorum sensing in S. aureus depends on the activities of
      membrane-associated proteins, such as AgrB, AgrC, and AgrD, we investigated
      whether AHLs perturbed S. aureus membrane functionality by determining their
      influence on the membrane dipole potential. From the binding curves obtained, a
      dissociation constant of 7 muM was obtained for 3-oxo-C12-HSL, indicating the
      presence of a specific saturable receptor, whereas no binding was observed for C4
      HSL. These data demonstrate that long-chain 3-oxo-substituted AHLs, such as 3-oxo
      C12-HSL, are capable of interacting with the S. aureus cytoplasmic membrane in a
      saturable, specific manner and at sub-growth-inhibitory concentrations, down
      regulating exotoxin production and both sarA and agr expression.

PMID- 16428735
TI  - HpaA is essential for Helicobacter pylori colonization in mice.
AB  - Infection with the human gastric pathogen Helicobacter pylori can give rise to
      chronic gastritis, peptic ulcer, and gastric cancer. All H. pylori strains
      express the surface-localized protein HpaA, a promising candidate for a vaccine
      against H. pylori infection. To study the physiological importance of HpaA, a
      mutation of the hpaA gene was introduced into a mouse-adapted H. pylori strain.
      To justify that the interruption of the hpaA gene did not cause any polar effects
      of downstream genes or was associated with a second site mutation, the protein
      expression patterns of the mutant and wild-type strains were characterized by two
      different proteomic approaches. Two-dimensional differential in-gel
      electrophoresis analysis of whole-cell extracts and subcellular fractionation
      combined with nano-liquid chromatography-Fourier transform ion cyclotron
      resonance mass spectrometry for outer membrane protein profiling revealed only
      minor differences in the protein profile between the mutant and the wild-type
      strains. Therefore, the mutant strain was tested for its colonizing ability in a
      well-established mouse model. While inoculation with the wild-type strain
      resulted in heavily H. pylori-infected mice, the HpaA mutant strain was not able
      to establish colonization. Thus, by combining proteomic analysis and in vivo
      studies, we conclude that HpaA is essential for the colonization of H. pylori in
      mice.

PMID- 16428736
TI  - Activation of the Vibrio cholerae SOS response is not required for intestinal
      cholera toxin production or colonization.
AB  - Cholera toxin, one of the main virulence factors of Vibrio cholerae, is encoded
      in the genome of CTXphi, a V. cholerae-specific lysogenic filamentous
      bacteriophage. Although the genes encoding cholera toxin, ctxAB, are known to
      have their own promoter, the toxin genes can also be transcribed from an upstream
      CTXphi promoter, PrstA. The V. cholerae SOS response to DNA damage induces the
      CTX prophage by stimulating gene expression initiating from PrstA. Here, we
      investigated whether ctxA mRNA levels increase along with the levels of the
      transcripts for the other CTXphi genes following stimulation of the V. cholerae
      SOS response. Treatment of V. cholerae with the SOS-inducing agent mitomycin C
      increased the level of ctxA mRNA approximately sevenfold, apparently by
      augmenting the activity of PrstA. However, using suckling mice as a model host,
      we found that intraintestinal ctxA transcription does not depend on PrstA. In
      fact, the suckling mouse intestine does not appear to be a potent inducer of the
      V. cholerae SOS response. Furthermore, alleviation of LexA-mediated repression of
      the V. cholerae SOS regulon was not required for V. cholerae growth in the
      suckling mouse intestine. Our observations suggest that pathogenicity of V.
      cholerae does not depend on its SOS response.

PMID- 16428737
TI  - Identification of a virulence-associated determinant, dihydrolipoamide
      dehydrogenase (lpd), in Mycoplasma gallisepticum through in vivo screening of
      transposon mutants.
AB  - To effectively analyze Mycoplasma gallisepticum for virulence-associated
      determinants, the ability to create stable genetic mutations is essential. Global
      M. gallisepticum mutagenesis is currently limited to the use of transposons.
      Using the gram-positive transposon Tn4001mod, a mutant library of 110
      transformants was constructed and all insertion sites were mapped. To identify
      transposon insertion points, a unique primer directed outward from the end of
      Tn4001mod was used to sequence flanking genomic regions. By comparing sequences
      obtained in this manner to the annotated M. gallisepticum genome, the precise
      locations of transposon insertions were discerned. After determining the
      transposon insertion site for each mutant, unique reverse primers were
      synthesized based on the specific sequences, and PCR was performed. The resultant
      amplicons were used as unique Tn4001mod mutant identifiers. This procedure is
      referred to as signature sequence mutagenesis (SSM). SSM permits the
      comprehensive screening of the M. gallisepticum genome for the identification of
      novel virulence-associated determinants from a mixed mutant population. To this
      end, chickens were challenged with a pool of 27 unique Tn4001mod mutants. Two
      weeks postinfection, the birds were sacrificed, and organisms were recovered from
      respiratory tract tissues and screened for the presence or absence of various
      mutants. SSM is a negative-selection screening technique whereby those mutants
      possessing transposon insertions in genes essential for in vivo survival are not
      recovered from the host. We have identified a virulence-associated gene encoding
      dihydrolipoamide dehydrogenase (lpd). A transposon insertion in the middle of the
      coding sequence resulted in diminished biologic function and reduced virulence of
      the mutant designated Mg 7.

PMID- 16428738
TI  - Activation of toll-like receptor 9 by DNA from different bacterial species.
AB  - Toll-like receptor 9 (TLR-9) recognizes unmethylated CpG dinucleotides which are
      abundant in prokaryotic DNA and yet are rare in eukaryotic DNA. Little is known
      about the significance of TLR-9 in terms of recognition of different bacterial
      DNA species. In this study HEK293 cells stably transfected with human TLR-9 were
      used to analyze the immunostimulatory properties of 15 bacterial DNA
      preparations. In addition, bacterial genome data were analyzed for the frequency
      of unmethylated cytosine-guanosine ([CG]) dinucleotides. We observed that DNA
      samples of different bacteria showed considerable differences in their potential
      to stimulate TLR-9. This correlated with the frequency of [CG] dinucleotides.
      Based upon data from our experiments the estimate of immunostimulatory bacterial
      DNA concentrations translated to as high as 10(9) bacteria/ml. Application of the
      transfection reagent DOTAP resulted in a more efficient delivery of DNA into the
      cell, and this went along with increased TLR-9 activation. The data indicate that
      bacterial DNA preparations from different species differ in their capacity to
      activate TLR-9, which is dependent on the individual [CG] content. Moreover,
      increased intracellular delivery results in a marked enhancement of
      immunostimulation.

PMID- 16428739
TI  - Interleukin 1alpha increases the susceptibility of rabbits to experimental
      viridans streptococcal endocarditis.
AB  - Major predisposing conditions for infective endocarditis (IE) are the presence of
      a cardiac platelet-fibrin vegetation and of circulating bacteria with relatively
      low susceptibility to microbicidal activity of blood platelets. The influence of
      proinflammatory conditions on development of IE is unknown. We studied the
      effects of the presence of a catheter, inserted to induce platelet-fibrin
      vegetations, and of the proinflammatory cytokine interleukin-1alpha in rabbit
      experimental IE. Leaving the catheter in place after challenge with viridans
      streptococci predisposed for experimental IE. IE susceptibility rapidly decreased
      between 0 to 6 h after catheter removal. The catheter did not predispose for IE
      by providing a site for bacterial adherence, as almost all explanted catheters
      were culture negative. To mimic the proinflammatory influence of the catheter,
      rabbits were injected with interleukin-1alpha at 24 h after catheter removal and
      at 0, 1, and 3 h before bacterial challenge. Interleukin-1alpha injected 3 h
      prior to challenge significantly increased IE incidence due to a platelet
      releasate-susceptible Streptococcus oralis strain, with rapidly increasing
      numbers of bacteria within the vegetations. IE due to the Streptococcus sanguis
      strain less susceptible to platelet releasate was not enhanced. We conclude that
      proinflammatory stimuli, either a catheter or interleukin-1alpha, enhanced
      susceptibility to IE due to the platelet releasate-susceptible S. oralis. As with
      rabbits, temporary intravascular proinflammatory conditions may predispose for IE
      in humans at risk for this serious infection.

PMID- 16428740
TI  - The protozoan Neospora caninum directly triggers bovine NK cells to produce gamma
      interferon and to kill infected fibroblasts.
AB  - Natural killer (NK) cells are considered to be key players in the early innate
      responses to protozoan infections, primarily indirectly by producing gamma
      interferon (IFN-gamma) in response to cytokines, like interleukin 12 (IL-12). We
      demonstrate that live, as well as heat-inactivated, tachyzoites of Neospora
      caninum, a Toxoplasma-like protozoan, directly trigger production of IFN-gamma
      from purified, IL-2-activated bovine NK cells. This response occurred
      independently of IL-12 but was increased by the addition of the cytokine. A
      similar IFN-gamma response was measured in cocultures of NK cells and N. caninum
      infected autologous fibroblasts. However, no NK cell-derived IFN-gamma response
      was detected when cells were cultured with soluble antigens from the organism,
      indicating that intact tachyzoites or nonsoluble components are necessary for NK
      cell triggering. Furthermore, N. caninum-infected autologous fibroblasts had
      increased susceptibility to NK cell cytotoxicity compared to uninfected
      fibroblasts. This cytotoxicity was largely mediated by a perforin-mediated
      mechanism. The activating receptor NKp46 was involved in cytotoxicity against
      fibroblasts but could not explain the increased cytotoxicity against infected
      targets. Interestingly, N. caninum tachyzoites were able to infect cultured NK
      cells, in which tachyzoites proliferated inside parasitophorous vacuoles.
      Together, these findings underscore the role of NK cells as primary responders
      during a protozoan infection, describe intracellular protozoan infection of NK
      cells in vitro for the first time, and represent the first functional study of
      purified bovine NK cells in response to infection.

PMID- 16428742
TI  - Safety and immunogenicity of an oral inactivated whole-cell pseudomonas
      aeruginosa vaccine administered to healthy human subjects.
AB  - This study examines the safety and immunogenicity of an oral, whole-cell
      Pseudomonas aeruginosa vaccine administered to healthy volunteers. Thirty
      subjects received an oral dose of Pseudostat in two timed, measured doses with
      serological follow-up to 56 days postvaccination. Following vaccination, several
      individuals were identified as antibody responders for all three immunoglobulin
      (Ig) isotypes tested, specifically against whole-cell P. aeruginosa extract and
      outer membrane proteins F and I. The mean pooled lipopolysaccharide antigen
      specific IgA showed the most significant and constant increases in titer
      postdose, with a similar increase in titer for whole-cell P. aeruginosa extract
      specific IgA. The results demonstrated an increased phagocytic ability of the
      selected macrophage cell line in post vaccination sera. Furthermore a significant
      increase in intracellular macrophage killing of opsonized P. aeruginosa was also
      demonstrated (82% on day 14 postdose) in the presence of the postvaccination
      sera. The safety component of the study did not show any vaccine-attributable
      adverse effects in any of the subjects, as documented by clinical evidence,
      hematology, and biochemistry profiles. We conclude that Pseudostat is safe and
      immunogenic in humans at this dose and that further studies to determine the
      appropriate dosage and efficacy are needed. In our study, we have shown that the
      most significant and sustained responses to oral vaccination in human adult
      volunteers were serum IgA levels and that pooled sera collected postimmunization
      have an increased capacity to promote opsonophagocytotic killing of P.
      aeruginosa.

PMID- 16428741
TI  - Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective
      hookworm larvae, is involved in tissue migration.
AB  - Infective larvae (L3) of nematodes secrete macromolecules that are critical to
      infection and establishment of the parasite in the host. The dog hookworm
      Ancylostoma caninum secretes an astacin-like metalloprotease, Ac-MTP-1, upon
      activation in vitro with host serum. Recombinant Ac-MTP-1 was expressed in the
      baculovirus/insect cell system as a secreted protein and was purified from
      culture medium by two separate methods, cation-exchange fast-performance liquid
      chromatography and gelatin-affinity chromatography. Recombinant MTP-1 was
      catalytically active and digested a range of native and denatured connective
      tissue substrates, including gelatin, collagen, laminin, and fibronectin. A dog
      was immunized with recombinant Ac-MTP-1 formulated with AS03 adjuvant, and the
      antiserum was used to immunolocalize the anatomic sites of expression within A.
      caninum L3 to secretory granules in the glandular esophagus and the channels that
      connect the esophagus to the L3 surface and to the cuticle. Antiserum inhibited
      the ability of recombinant MTP-1 to digest collagen by 85% and inhibited larval
      migration through tissue in vitro by 70 to 75%, in contrast to just 5 to 10%
      inhibition obtained with preimmunization serum. The metalloprotease inhibitors
      EDTA and 1,10-phenanthroline also reduced the penetration of L3 through skin in
      vitro by 43 to 61%. The data strongly suggest that Ac-MTP-1 is critical for the
      invasion process of hookworm larvae, and moreover, that antibodies against the
      enzyme can neutralize its function and inhibit migration.

PMID- 16428743
TI  - A live-attenuated Pseudomonas aeruginosa vaccine elicits outer membrane protein
      specific active and passive protection against corneal infection.
AB  - Pseudomonas aeruginosa can cause sight-threatening corneal infections in humans,
      particularly those who wear contact lenses. We have previously shown that a live
      attenuated P. aeruginosa vaccine given intranasally protected mice against acute
      lethal pneumonia in a lipopolysaccharide (LPS) serogroup-specific manner. In the
      current study, we evaluated the protective and therapeutic efficacies, as well as
      the target antigens, of this vaccine in a murine corneal infection model. C3H/HeN
      mice were nasally immunized with the vaccine (an aroA deletion mutant of strain
      PAO1, designated PAO1DeltaaroA) or with Escherichia coli as a control and were
      challenged 3 weeks later by inoculating the scratch-injured cornea with P.
      aeruginosa. For passive prophylaxis and therapy, we utilized a serum raised in
      rabbits nasally immunized with PAO1DeltaaroA or E. coli. Outcome measures
      included corneal pathology scores and, in some experiments, reductions in total
      and internalized bacterial CFU. We found that both active and passive
      immunization reduced corneal pathology scores after challenge with a variety of
      P. aeruginosa strains, including several serogroup-heterologous strains. Even
      when given therapeutically starting as late as 24 h after infection, the rabbit
      antiserum to PAO1DeltaaroA was effective at reducing corneal pathology scores.
      Immunotherapy of established infections also reduced the numbers of total and
      internalized corneal P. aeruginosa bacteria. Experiments using absorbed sera
      showed that the protective antibodies are specific to outer membrane proteins.
      Thus, live-attenuated P. aeruginosa vaccines delivered nasally protect against
      corneal infections in mice and potentially can be used to prepare passive therapy
      reagents for the treatment of established P. aeruginosa corneal infections caused
      by diverse LPS serogroups.

PMID- 16428745
TI  - Comparative safety and immunogenicity of two attenuated enterotoxigenic
      Escherichia coli vaccine strains in healthy adults.
AB  - A vaccine against enterotoxigenic Escherichia coli (ETEC) is needed to prevent
      diarrheal illness among children in developing countries and at-risk travelers.
      Two live attenuated ETEC strains, PTL002 and PTL003, which express the ETEC
      colonization factor CFA/II, were evaluated for safety and immunogenicity. In a
      randomized, double-blind, placebo-controlled trial, 19 subjects ingested one
      dose, and 21 subjects ingested two doses (days 0 and 10) of PTL-002 or PTL-003 at
      2 x 10(9) CFU/dose. Anti-CFA/II mucosal immune responses were determined from the
      number of antibody-secreting cells (ASC) in blood measured by enzyme-linked
      immunospot assay, the antibody in lymphocyte supernatants (ALS) measured by
      enzyme-linked immunosorbent assay (ELISA), and fecal immunoglobulin A (IgA)
      levels determined by ELISA. Time-resolved fluorescence (TRF) ELISA was more
      sensitive than standard colorimetric ELISA for measuring serum antibody responses
      to CFA/II and its components, CS1 and CS3. Both constructs were well tolerated.
      Mild diarrhea occurred after 2 of 31 doses (6%) of PTL-003. PTL-003 produced more
      sustained intestinal colonization than PTL-002 and better IgA response rates: 90%
      versus 55% (P = 0.01) for anti-CFA/II IgA-ASCs, 55% versus 30% (P = 0.11) for
      serum anti-CS1 IgA by TRF, and 65% versus 25% (P = 0.03) for serum anti-CS3 IgA
      by TRF. Serum IgG response rates to CS1 or CS3 were 55% in PTL-003 recipients and
      15% in PTL-002 recipients (P = 0.02). Two doses of either strain were not
      significantly more immunogenic than one. Based on its superior immunogenicity,
      which was comparable to that of a virulent ETEC strain and other ETEC vaccine
      candidates, PTL-003 will be developed further as a component of a live, oral
      attenuated ETEC vaccine.

PMID- 16428744
TI  - Transfer of antigen-pulsed dendritic cells induces specific T-Cell proliferation
      and a therapeutic effect against long-term Helicobacter pylori infection in mice.
AB  - Helicobacter pylori causes persistent infection of the stomach and results in
      chronic gastritis and peptic ulcers. Jaws II cells, derived from mouse bone
      marrow, were pulsed with live or formalin-killed or whole-cell sonicates (WCS) of
      H. pylori. Representative cell surface molecules were expressed at substantial
      levels on Jaws II cells, indicating that appropriate maturation of the cells was
      achieved with the three H. pylori antigens without any significant differences.
      H. pylori WCS-pulsed Jaws II cells secreted a significant amount of tumor
      necrosis factor alpha into the culture supernatant. The naive T cells exposed to
      the WCS-pulsed Jaws II cells showed significant proliferation and gamma
      interferon (IFN-gamma) and interleukin-10 (IL-10) production in vitro. A 2-log
      reduction in the number of colonizing bacteria was observed in the mice treated
      with the WCS-pulsed Jaws II cells; however, no significant reductions were
      achieved in mice treated with Jaws II cells pulsed with other H. pylori antigens.
      Up-regulated production of IFN-gamma and IL-10 was observed in the stomachs of
      the mice treated with the WCS-pulsed Jaws II cells, which is consistent with the
      result obtained in vitro. There were no differences in gastritis scores or H.
      pylori-specific antibody titers among the mice treated with Jaws II cells pulsed
      with the three different H. pylori antigens. The results suggest that Th1 cell
      mediated immunity in combination with Th2 cell-mediated immunity plays a role in
      reducing colonizing bacterial numbers in mice with chronic H. pylori infections.

PMID- 16428746
TI  - Stimulation of CD8+ T cells following diphtheria toxin-mediated antigen delivery
      into dendritic cells.
AB  - Recognition and clearance of many intracellular pathogens requires the activation
      and subsequent effector functions of CD8+ T lymphocytes. To stimulate CD8+ T
      cells by immunization, the target antigens must be delivered into the cytosol of
      host cells. There they can be processed into peptides and presented in the
      context of major histocompatibility complex class I molecules to antigen-specific
      CD8+ T cells. One method of delivering antigens into the cytosol is to fuse them
      to modified bacterial toxins that are able to enter mammalian cells. The
      expression pattern of the toxin receptors in the host will determine the cell
      population that the toxin fusion protein targets and will thus restrict antigen
      specific T-cell recognition to the same population. In this study we describe the
      development and characterization of a diphtheria toxin (DT)-based antigen
      delivery system. Using CD11c-DTR transgenic mice that express the DT receptor in
      dendritic cells (DC), this system allows for targeted delivery of CD8+ T-cell
      antigen to DC. We show that antigen-specific CD8+ T cells proliferate in CD11c
      DTR mice following immunization with catalytically inactive DT-antigen fusion
      proteins. We also show that a toxin-based system that restricts antigen delivery
      to DC results in more robust antigen-specific CD8+ T-cell proliferation than a
      toxin-based system that does not restrict delivery to a particular cell type.
      These results have implications for vaccine design, and they suggest that use of
      a toxin-based vector to target antigen to DC may be an effective way to induce a
      CD8+ T-cell response.

PMID- 16428747
TI  - Cytokine response and survival of mice immunized with an adenovirus expressing
      Bacillus anthracis protective antigen domain 4.
AB  - Adenovirus vectors are promising for use in vaccinating against potential agents
      of bioterrorism and emerging infections because of their proven safety in humans
      and their ability to elicit rapid immune responses. Here, we describe the
      construction and evaluation of an adenovirus vaccine expressing domain 4 of
      Bacillus anthracis protective antigen, Ad.D4. Ad.D4 elicited antibodies to
      protective antigen 14 days after a single intramuscular injection, which were
      further increased upon boosting. Furthermore, two doses of Ad.D4 4 weeks apart
      were sufficient to protect 67% of mice from toxin challenge. Additionally, we
      have characterized the release of inflammatory cytokines from vaccinated mice
      after lethal-toxin challenge. We demonstrate that interleukin 1beta (IL-1beta)
      levels in mice that survive lethal toxin challenge are similar to levels in
      nonsurvivors and that IL-6 levels are higher in survivors than in nonsurvivors.
      These findings suggest that lethal-toxin-mediated death may not be a direct
      result of inflammatory-cytokine release.

PMID- 16428748
TI  - Human monoclonal anti-protective antigen antibody completely protects rabbits and
      is synergistic with ciprofloxacin in protecting mice and guinea pigs against
      inhalation anthrax.
AB  - Prevention of inhalation anthrax requires early and extended antibiotic therapy,
      and therefore, alternative treatment strategies are needed. We investigated
      whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would
      protect mice, guinea pigs, and rabbits against anthrax. Control animals
      challenged with Bacillus anthracis Ames spores by the intranasal route died
      within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in
      the murine model, but its efficacy was notably better in guinea pigs. When Swiss
      Webster mice, challenged with five 50% lethal doses (LD50s) of anthrax spores,
      were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined
      with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the
      mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone
      showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was
      combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and
      administered to guinea pigs for 6 days, synergistic protection against anthrax
      was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20
      mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge
      with 100 LD50s of B. anthracis Ames spores, and 100% of the rabbits survived
      rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6,
      and 12 h after challenge with anthrax spores resulted in 100% survival; however,
      delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%,
      respectively. Serological analysis of sera from various surviving animals 30 days
      postprimary infection showed development of a species-specific PA enzyme-linked
      immunosorbent assay antibody titer that correlated with protection against
      reinfection. Taken together, the effectiveness of human anti-PA antibody alone or
      in combination with low ciprofloxacin levels may provide the basis for an
      improved strategy for prophylaxis or treatment following inhalation anthrax
      infection.

PMID- 16428749
TI  - Correlation of molecular characteristics, isotype, and in vitro functional
      activity of human antipneumococcal monoclonal antibodies.
AB  - Structure-function correlations of pneumococcal antibodies are important in
      predicting how changes in the pneumococcus (Pnc)-specific B-cell repertoire will
      influence humoral immunity against invasive Pnc disease. Using a unique panel of
      human hybridomas derived from memory B cells after pneumococcal conjugate
      vaccination, we analyzed the structure-function relationship of nine monoclonal
      antibodies (MAbs) reactive to Pnc polysaccharides. The avidities of the
      antibodies correlated with the avidity of donor immune serum (R, 0.7; P < 0.025),
      and this relationship was particularly strong for immunoglobulin A clones (R, 1;
      P < 0.0005), suggesting that the MAbs may represent important clones contributing
      to serological memory. Common heavy-light chain combinations and amino acid
      replacement mutations were seen for clones with the same serospecificity from
      different individuals. The two highest-avidity MAbs used Vh3-48, and two MAbs
      with the same serospecificity, using the same V gene pairings (Vh3-7 and Vk2A17),
      had similar avidities, suggesting that canonical V gene use makes an important
      contribution to avidity. Although all clones had mutation levels consistent with
      their being derived from memory B cells, low levels of replacement mutation were
      associated with high avidities. This relationship was strongest for Vh genes (R,
      0.8; P < 0.01). Opsonophagocytosis was demonstrated for all clones, and there was
      a trend toward clones using canonical genes with low levels of mutation having
      high opsonophagocytic activities (R, 0.5). These data suggest that the use of
      canonical genes in the Pnc antibody response is associated with highly functional
      antibodies and that most somatic mutations seen in these genes are not antigen
      selected.

PMID- 16428750
TI  - Identification of proteins secreted via Vibrio parahaemolyticus type III
      secretion system 1.
AB  - Vibrio parahaemolyticus, a gram-negative marine bacterium, is an important
      pathogen causing food-borne gastroenteritis or septicemia. Recent genome
      sequencing of the RIMD2210633 strain (a Kanagawa phenomenon-positive clinical
      isolate of serotype O3:K6) revealed that the strain has two sets of gene clusters
      that encode the type III secretion system (TTSS) apparatus. The first cluster,
      TTSS1, is located on the large chromosome, and the second, TTSS2, is on the small
      chromosome. Previously, we reported that TTSS1 is involved in the cytotoxicity of
      the RIMD2210633 strain against HeLa cells. Here, we analyzed proteins secreted
      via the TTSS apparatus encoded by TTSS1 by using two-dimensional gel
      electrophoresis and identified the proteins encoded by genes VP1680, VP1686, and
      VPA450. To investigate the roles of those secreted proteins, we constructed and
      analyzed a series of deletion mutants. Flow cytometry analysis using fluorescence
      activated cell sorting with fluorescein isothiocyanate-labeled annexin V
      demonstrated that the TTSS1-dependent cell death was by apoptosis. The
      cytotoxicity to HeLa cells was related to one of the newly identified secreted
      proteins encoded by VP1680. Adenylate cyclase fusion protein studies proved that
      the newly identified secreted proteins were translocated into HeLa cells. Thus,
      these appear to be the TTSS effector proteins in V. parahaemolyticus.

PMID- 16428752
TI  - Role for inducible costimulator in control of Salmonella enterica serovar
      Typhimurium infection in mice.
AB  - Inducible costimulator (ICOS) is expressed on activated T cells and plays a key
      role in sustaining and enhancing the effector function of CD4 T cells. Given the
      function of this molecule in sustaining T-cell responses, we reasoned that ICOS
      might play an important role in a prolonged infection model, such as Salmonella
      infection of mice. To test this hypothesis, wild-type (WT) and ICOS-deficient
      (ICOS-/-) mice were infected systemically with a Salmonella enterica serovar
      Typhimurium strain expressing the chicken ovalbumin gene (Salmonella-OVA). ICOS-/
      mice exhibited greater splenomegaly than WT mice and showed delayed bacterial
      clearance. The acquired immune response in this model was slow to develop.
      Maximal T-cell responses to Salmonella-OVA were detected at 3 weeks postinfection
      in both WT and ICOS-/- mice. CD4 T-cell-dependent gamma interferon production and
      a class switch to immunoglobulin G2a were severely reduced in ICOS-/- mice. ICOS
      /- mice also exhibited a substantial defect in antigen-specific CD8 T-cell
      responses. In vitro, the effect of anti-ICOS on CD8 T-cell division was greater
      when CD8 T cells rather than CD4 T cells expressed ICOS, suggesting that the in
      vivo effects of ICOS on CD8 T cells could be direct. Taken together, these
      studies show that ICOS plays a critical role in control of Salmonella infection
      in mice, with effects on antibody, Th1, and CD8 T-cell responses.

PMID- 16428751
TI  - The Bordetella bronchiseptica type III secretion system inhibits gamma interferon
      production that is required for efficient antibody-mediated bacterial clearance.
AB  - Several species of pathogenic microorganisms have developed strategies to survive
      and persist in vital organs which are normally maintained as sterile by the
      generation of strong immune responses. Here, we report an immunomodulation
      involving the Bordetella bronchiseptica type III secretion system (TTSS) which
      contributes to bacterial survival in the lower respiratory tract of the host. The
      prolonged persistence of B. bronchiseptica that was observed in gamma interferon
      (IFN-gamma)-/- mice indicates that the efficient clearance of bacteria from the
      lower respiratory tract requires not only B cells and antibodies but also IFN
      gamma production. Our data also suggest that interleukin-10 (IL-10)-producing
      splenocytes are generated early during infection and that IL-10 inhibits IFN
      gamma-producing cells and delays the clearance of B. bronchiseptica from the
      lungs. The TTSS of B. bronchiseptica inhibits the generation of IFN-gamma
      producing splenocytes and is required for long-term bacterial persistence in the
      lower respiratory tract in wild-type mice. This suggests that a mechanism
      involving the modulation of IFN-gamma production by the TTSS facilitates B.
      bronchiseptica survival in the lower respiratory tract.

PMID- 16428753
TI  - Construction and phase I clinical evaluation of the safety and immunogenicity of
      a candidate enterotoxigenic Escherichia coli vaccine strain expressing
      colonization factor antigen CFA/I.
AB  - Oral delivery of toxin-negative derivatives of enterotoxigenic Escherichia coli
      (ETEC) that express colonization factor antigens (CFA) with deletions of the
      aroC, ompC, ompF, and toxin genes may be an effective approach to vaccination
      against ETEC-associated diarrhea. We describe the creation and characterization
      of an attenuated CFA/I-expressing ETEC vaccine candidate, ACAM2010, from a
      virulent isolate in which the heat-stable enterotoxin (ST) and CFA/I genes were
      closely linked and on the same virulence plasmid as the enteroaggregative E. coli
      heat-stable toxin (EAST1) gene. A new suicide vector (pJCB12) was constructed and
      used to delete the ST and EAST1 genes and to introduce defined deletion mutations
      into the aroC, ompC, and ompF chromosomal genes. A phase I trial, consisting of
      an open-label dose escalation phase in 18 adult outpatient volunteers followed by
      a placebo-controlled double-blind phase in an additional 31 volunteers, was
      conducted. The vaccine was administered in two formulations, fresh culture and
      frozen suspension. These were both well tolerated, with no evidence of
      significant adverse events related to vaccination. Immunoglobulin A (IgA) and IgG
      antibody-secreting cells specific for CFA/I were assayed by ELISPOT. Positive
      responses (greater than twofold increase) were seen in 27 of 37 (73%) subjects
      who received the highest dose level of vaccine (nominally 5 x 10(9) CFU). Twenty
      nine of these volunteers were secreting culturable vaccine organisms at day 3
      following vaccination; five were still positive on day 7, with a single isolation
      on day 13. This live attenuated bacterial vaccine is safe and immunogenic in
      healthy adult volunteers.

PMID- 16428754
TI  - Regulation of type 1 fimbriae by unlinked FimB- and FimE-like recombinases in
      uropathogenic Escherichia coli strain CFT073.
AB  - Genomic DNA sequence analysis of the uropathogenic Escherichia coli strain CFT073
      revealed that besides the fimB and fimE recombinase genes that control the type 1
      pilus fim phase switch, there are three additional fimB- and fimE-like genes:
      ipuA, ipuB, and ipbA. Alignment of the predicted amino acid sequences showed that
      the five recombinases range in sequence similarity from 63 to 70%. An
      epidemiological survey indicates that ipuA and ipuB are present and linked next
      to the dsdCXA locus in 24 of 67 uropathogenic E. coli strains but are found in
      only 1 of 15 normal human fecal isolates. The ipbA sequence located next to the
      betABIT locus was found in 42 of 67 uropathogenic isolates and 8 of 15 of the
      commensal strains. We show that two of these recombinases, those encoded by ipuA
      and ipbA, can function at the type 1 pilus fim switch. In a CFT073 deletion
      mutant lacking all five recombinase genes, recombinant ipuA or ipbA provided in
      trans inverted the fim element from the off state to the on state. When a fim OFF
      CFT073 DeltafimBE mutant was used to infect the urinary tracts of mice, a switch
      to the fim on state was detected within 24 h in bacteria recovered from urine,
      the bladder, and the kidneys. A fim OFF CFT073 DeltafimBE ipuB ipbA mutant also
      demonstrated the ability to switch from the fim off state to the on state during
      mouse infection. CFT073 recombinase mutants derived from isolates in either the
      fim on or off state showed a reciprocal relationship for motility. Switches from
      a nonmotile to a motile phenotype and from a fim on to off genotype were observed
      in fim ON CFT073 DeltafimBE ipuAB ipbA mutants when ipuA or fimB was provided in
      trans. Together these results indicate that ipuA has fimB-like on-to-off and off
      to-on fim switching activity and that ipbA has the ability to switch fim from the
      off to the on orientation.

PMID- 16428755
TI  - Cre reporter system to monitor the translocation of type III secreted proteins
      into host cells.
AB  - Central to the study of type III secretion systems is the availability of
      reporter systems to monitor bacterial protein translocation into host cells. We
      report here the development of a bacteriophage P1 Cre recombinase-based system to
      monitor the translocation of bacterial proteins into mammalian cells.
      Bacteriophage P1 Cre recombinase fused to the secretion and translocation signals
      of Salmonella enterica serovar Typhimurium of the type III secreted protein SopE
      was secreted in a type III secretion system-dependent fashion. More importantly,
      the SopE-Cre chimera was translocated into host cells via the type III secretion
      system and activated the expression of luciferase and green fluorescent protein
      reporters of Cre recombinase activity.

PMID- 16428756
TI  - Virulence of Staphylococcus aureus small colony variants in the Caenorhabditis
      elegans infection model.
AB  - Small colony variants (SCVs) of Staphylococcus aureus are slow-growing
      morphological variants that have been implicated in persistent, relapsing, and
      antibiotic-resistant infections. The altered phenotype of SCVs in most strains
      has been attributed to defects in electron transport due to mutations in hemin or
      menadione biosynthesis. The pathogenic capacity of SCVs compared to
      phenotypically normal strains is variable depending on the attribute examined,
      with some studies showing reduced virulence of SCVs and others demonstrating
      normal or heightened virulence. Recently, the nematode Caenorhabditis elegans has
      been successfully employed as an alternative host to investigate virulence
      mechanisms of a variety of bacterial pathogens, including S. aureus. In this
      study, we show that clinical SCVs as well as hemB- and menD-deficient mutants of
      S. aureus are greatly reduced in virulence in the C. elegans infection model.

PMID- 16428757
TI  - Identification of novel gammadelta T-cell subsets following bacterial infection
      in the absence of Vgamma1+ T cells: homeostatic control of gammadelta T-cell
      responses to pathogen infection by Vgamma1+ T cells.
AB  - Although gammadelta T cells are a common feature of many pathogen-induced immune
      responses, the factors that influence, promote, or regulate the response of
      individual gammadelta T-cell subsets to infection is unknown. Here we show that
      in the absence of Vgamma1+ T cells, novel subsets of gammadelta T cells,
      expressing T-cell receptor (TCR)-Vgamma chains that normally define
      TCRgammadelta+ dendritic epidermal T cells (DETCs) (Vgamma5+), intestinal
      intraepithelial lymphocytes (iIELs) (Vgamma7+), and lymphocytes associated with
      the vaginal epithelia (Vgamma6+), are recruited to the spleen in response to
      bacterial infection in TCR-Vgamma1-/- mice. By comparison of phenotype and
      structure of TCR-Vgamma chains and/or -Vdelta chains expressed by these novel
      subsets with those of their epithelium-associated counterparts, the Vgamma6+ T
      cells elicited in infected Vgamma1-/- mice were shown to be identical to those
      found in the reproductive tract, from where they are presumably recruited in the
      absence of Vgamma1+ T cells. By contrast, Vgamma5+ and Vgamma7+ T cells found in
      infected Vgamma1-/- mice were distinct from Vgamma5+ DETCs and Vgamma7+ iIELs.
      Functional analyses of the novel gammadelta T-cell subsets identified for
      infected Vgamma1-/- mice showed that whereas the Vgamma5+ and Vgamma7+ subsets
      may compensate for the absence of Vgamma1+ T cells by producing similar
      cytokines, they do not possess cytocidal activity and they cannot replace the
      macrophage homeostasis function of Vgamma1+ T cells. Collectively, these findings
      identify novel subsets of gammadelta T cells, the recruitment and activity of
      which is under the control of Vgamma1+ T cells.

PMID- 16428758
TI  - Dendritic cell immaturity during infancy restricts the capacity to express
      vaccine-specific T-cell memory.
AB  - The capacity of the immune system in infants to develop stable T-cell memory in
      response to vaccination is attenuated, and the mechanism(s) underlying this
      developmental deficiency in humans is poorly understood. The present study
      focuses on the capacity for expression of in vitro recall responses to tetanus
      and diphtheria antigens in lymphocytes from 12-month-old infants vaccinated
      during the first 6 months of life. We demonstrate that supplementation of infant
      lymphocytes with "matured" dendritic cells (DC) cultured from autologous CD14+
      precursors unmasks previously covert cellular immunity in the form of Th2-skewed
      cytokine production. Supplementation of adult lymphocytes with comparable
      prematured autologous DC also boosted vaccine-specific T-cell memory expression,
      but in contrast to the case for the infants, these cytokine responses were
      heavily Th1 skewed. Compared to adults, infants had significantly fewer
      circulating myeloid DC (P < 0.0001) and plasmacytoid DC (P < 0.0001) as a
      proportion of peripheral blood mononuclear cells. These findings suggest that
      deficiencies in the numbers of antigen-presenting cells and their functional
      competence at 12 months of age limit the capacity to express effector memory
      responses and are potentially a key factor in reduced vaccine responsiveness in
      infants.

PMID- 16428759
TI  - Flagellin is an effective adjuvant for immunization against lethal respiratory
      challenge with Yersinia pestis.
AB  - Gram-negative flagellin, a Toll-like receptor 5 (TLR5) agonist, is a potent
      inducer of innate immune effectors such as cytokines and nitric oxide. In the
      lung, flagellin induces a localized and transient innate immune response
      characterized by neutrophil infiltration and the production of cytokines and
      chemokines. In view of the extraordinary potency of flagellin as an inducer of
      innate immunity and the contribution of innate responses to the development of
      adaptive immunity, we evaluated the efficacy of recombinant Salmonella flagellin
      as an adjuvant in an acellular plague vaccine. Mice immunized intranasally or
      intratracheally with the F1 antigen of Yersinia pestis and flagellin exhibited
      dramatic increases in anti-F1 plasma immunoglobulin G (IgG) titers that remained
      stable over time. In contrast, control mice had low or undetectable antibody
      responses. The IgG1/IgG2a ratio of antibody titers against F1 in immunized mice
      is consistent with a Th2 bias. However, no significant antigen-specific IgE
      production was detected. Interferons, tumor necrosis factor alpha, and
      interleukin-6 were not essential for the adjuvant effects of flagellin.
      Preexisting antiflagellin antibodies had no significant effect on the adjuvant
      activity of flagellin. Importantly, intranasal immunization with flagellin and
      the F1 antigen was protective against intranasal challenge with virulent Y.
      pestis CO92, with 93 to 100% survival of immunized mice. Lastly, vaccination of
      cynomolgus monkeys with flagellin and a fusion of the F1 and V antigens of Y.
      pestis induced a robust antigen-specific IgG antibody response.

PMID- 16428760
TI  - PsrA is a positive transcriptional regulator of the type III secretion system in
      Pseudomonas aeruginosa.
AB  - The type III secretion system (TTSS) of Pseudomonas aeruginosa is induced in vivo
      upon contact with eukaryotic cells and in vitro by calcium depletion in culture
      medium. We have observed a previously identified protein, PsrA, necessary for
      full activation of TTSS gene expression in P. aeruginosa. Electrophoretic
      mobility shift assays showed that recombinant PsrA could bind to the exsCEBA
      promoter region. A mutant with a deletion in the psrA gene was constructed. Using
      transcriptional fusions, we demonstrated that PsrA is required for the full
      activation of transcription of the TTSS regulatory operon exsCEBA and effector
      exoS, although the deletion mutant still responded to calcium depletion, to
      serum, and to host cell contact. The psrA mutant showed a marked decrease in the
      secretion of the type III effectors and weak resistance to phagocyte-like PLB-985
      cells. The defect in TTSS transcription and secretion in the psrA mutant could be
      complemented by expression in trans of psrA. PsrA was previously identified as a
      transcriptional activator of RpoS, a central regulator during stationary phase.
      We confirmed with our strain that RpoS has a negative effect on TTSS gene
      expression. Taken altogether, these results suggest that PsrA is a newly
      identified activator that is involved in the expression of the TTSS by enhancing
      the exsCEBA transcriptional level.

PMID- 16428761
TI  - Role of gluconeogenesis and the tricarboxylic acid cycle in the virulence of
      Salmonella enterica serovar Typhimurium in BALB/c mice.
AB  - In Salmonella enterica serovar Typhimurium, the Cra protein (catabolite
      repressor/activator) regulates utilization of gluconeogenic carbon sources by
      activating transcription of genes in the gluconeogenic pathway, the glyoxylate
      bypass, the tricarboxylic acid (TCA) cycle, and electron transport and repressing
      genes encoding glycolytic enzymes. A serovar Typhimurium SR-11 Deltacra mutant
      was recently reported to be avirulent in BALB/c mice via the peroral route,
      suggesting that gluconeogenesis may be required for virulence. In the present
      study, specific SR-11 genes in the gluconeogenic pathway were deleted (fbp, glpX,
      ppsA, and pckA), and the mutants were tested for virulence in BALB/c mice. The
      data show that SR-11 does not require gluconeogenesis to retain full virulence
      and suggest that as yet unidentified sugars are utilized by SR-11 for growth
      during infection of BALB/c mice. The data also suggest that the TCA cycle
      operates as a full cycle, i.e., a sucCD mutant, which prevents the conversion of
      succinyl coenzyme A to succinate, and an DeltasdhCDA mutant, which blocks the
      conversion of succinate to fumarate, were both attenuated, whereas both an SR-11
      DeltaaspA mutant and an SR-11 DeltafrdABC mutant, deficient in the ability to run
      the reductive branch of the TCA cycle, were fully virulent. Moreover, although it
      appears that SR-11 replenishes TCA cycle intermediates from substrates present in
      mouse tissues, fatty acid degradation and the glyoxylate bypass are not required,
      since an SR-11 DeltafadD mutant and an SR-11 DeltaaceA mutant were both fully
      virulent.

PMID- 16428762
TI  - Genetic and phenotypic diversity of quorum-sensing systems in clinical and
      environmental isolates of Vibrio cholerae.
AB  - Vibrio cholerae is the causative agent of cholera, a severe and devastating
      diarrheal disease. V. cholerae lives naturally in various aquatic habitats during
      interepidemic periods. Recent studies reveal that quorum-sensing systems, which
      exist in many bacteria and help them monitor their population densities and
      regulate various cellular functions, control V. cholerae pathogenesis, biofilm
      formation, and protease production. In this study we surveyed quorum-sensing
      systems in 16 geographically diverse V. cholerae strains from epidemic-causing O1
      and O139 strains as well as non-O1/non-O139 and environmental isolates and
      discovered an unexpectedly high rate of dysfunctional components. We also found
      that a functional quorum-sensing system conferred a survival advantage on
      bacteria in biofilms when the bacteria were exposed to seawater, though quorum
      sensing was less important to survival in a planktonic state under the same
      conditions. These findings suggest that variations in quorum-sensing systems are
      due to environmental selective pressures and might be beneficial to V. cholerae's
      fitness under certain conditions found in its natural reservoirs.

PMID- 16428763
TI  - The Helicobacter pylori urease B subunit binds to CD74 on gastric epithelial
      cells and induces NF-kappaB activation and interleukin-8 production.
AB  - The pathogenesis associated with Helicobacter pylori infection is the result of
      both bacterial factors and the host response. We have previously shown that H.
      pylori binds to CD74 on gastric epithelial cells. In this study, we sought to
      identify the bacterial protein responsible for this interaction. H. pylori urease
      from a pool of bacterial surface proteins was found to coprecipitate with CD74.
      To determine how urease binds to CD74, we used recombinant urease A and B
      subunits. Recombinant urease B was found to bind directly to CD74 in
      immunoprecipitation and flow cytometry studies. By utilizing both recombinant
      urease subunits and urease B knockout bacteria, the urease B-CD74 interaction was
      shown to induce NF-kappaB activation and interleukin-8 (IL-8) production. This
      response was decreased by blocking CD74 with monoclonal antibodies. Further
      confirmation of the interaction of urease B with CD74 was obtained using a
      fibroblast cell line transfected with CD74 that also responded with NF-kappaB
      activation and IL-8 production. The binding of the H. pylori urease B subunit to
      CD74 expressed on gastric epithelial cells presents a novel insight into a
      previously unrecognized H. pylori interaction that may contribute to the
      proinflammatory immune response seen during infection.

PMID- 16428764
TI  - Fas ligand deficiency impairs host inflammatory response against infection with
      the spirochete Borrelia burgdorferi.
AB  - Lyme disease represents a complex response to Borrelia burgdorferi that involves
      both bacterial factors as well as host responses. This results in an inflammatory
      reaction at several sites, including the synovial lining of joints. Synovial
      tissues of inflamed joints contain cells expressing high levels of Fas and Fas
      ligand (FasL). Although Fas stimulation is typically associated with cell death,
      it can also transmit stimulatory signals to certain cell types. Among these are
      dendritic cells and macrophages, which are abundant in inflamed synovium. To
      better assess the role of FasL in the pathogenesis of Lyme arthritis, we
      evaluated the response to B. burgdorferi infection in C3H/HeJgld mice that bear a
      nonfunctional mutation in FasL. Compared to wild-type C3H+/+ mice, C3Hgld mice
      had a similar bacterial burden and antibody response 2 weeks and 4 weeks
      following infection, but they manifested a significantly reduced Borrelia
      specific cytokine response. In addition, C3Hgld mice developed a greatly reduced
      incidence and severity of arthritis. The findings document a contribution of FasL
      to the host inflammatory response to B. burgdorferi.

PMID- 16428765
TI  - Conservation and diversity of HMW1 and HMW2 adhesin binding domains among
      invasive nontypeable Haemophilus influenzae isolates.
AB  - The pathogenesis of nontypeable Haemophilus influenzae (NTHi) begins with
      adhesion to the rhinopharyngeal mucosa. In almost 80% of NTHi clinical isolates,
      the HMW proteins are the major adhesins. The prototype HMW1 and HMW2 proteins,
      identified in NTHi strain 12, exhibit different binding specificities. The two
      binding domains have been localized in regions of maximal sequence dissimilarity
      (40% identity, 58% similarity). Two areas within these binding domains have been
      found essential for full level adhesive activity (designated the core-binding
      domains). To investigate the conservation and diversity of the HMW1 and HMW2 core
      binding domains among isolates, PCR and DNA sequencing were used. First, we
      separately amplified the hmw1A-like and hmw2A-like structural genes in nine
      invasive NTHi isolates, discovering two new hmwA alleles, whose sequences are
      herein reported. Then, the hmw1A-like and hmw2A-like PCR products were used as
      the template in nested PCR to produce amplicons encompassing the encoding
      sequences of the two core-binding domains. In-depth sequence analysis was then
      performed among sequences of each group, with the support of specific computer
      programs. Overall, extensive sequence diversity among isolates was highlighted.
      However, similarity plots showed patterns consisting of peaks of relatively high
      similarity alternating with strongly divergent regions. The phylogenetic tree
      clearly indicated the HMW1-like and HMW2-like core-binding domain sequences as
      two clusters. Distinct sets of conserved amino acid motifs were identified within
      each group of sequences using the MEME/MOTIFSEARCH tool. Since HMW adhesins could
      represent candidates for future vaccines, identification of specific patterns of
      conserved motifs in otherwise highly variable regions is of great interest.

PMID- 16428766
TI  - Mn2+-dependent regulation of multiple genes in Streptococcus pneumoniae through
      PsaR and the resultant impact on virulence.
AB  - The concentration of Mn2+ is 1,000-fold higher in secretions than it is at
      internal sites of the body, making it a potential signal by which bacteria can
      sense a shift from a mucosal environment to a more invasive site. PsaR, a metal
      dependent regulator in Streptococcus pneumoniae, was found to negatively affect
      the transcription of psaBCA, pcpA, rrgA, rrgB, rrgC, srtBCD, and rlrA in the
      presence of Mn2+. psaBCA encode an ABC-type transporter for Mn2+. pcpA, rrgA,
      rrgB, and rrgC encode several outer surface proteins. srtBCD encode a cluster of
      sortase enzymes, and rlrA encodes a transcriptional regulator. Steady-state RNA
      levels are high under low Mn2+ concentrations in the wild-type strain and are
      elevated under both high and low Mn2+ concentrations in a psaR mutant strain.
      RlrA is an activator of rrgA, rrgB, rrgC, and srtBCD (D. Hava and A. Camilli,
      Mol. Microbiol. 45:1389-1406, 2002), suggesting that PsaR may indirectly control
      these genes through rlrA, while PsaR-dependent repression of psaBCA, pcpA, and
      rlrA transcription is direct. The impact of Mn2+-dependent regulation on
      virulence was further examined in mouse models of pneumonia and nasopharyngeal
      carriage. The abilities of DeltapsaR, pcpA, and DeltapsaR DeltapcpA mutant
      strains to colonize the lung were reduced compared to those of the wild type,
      confirming that both PcpA-mediated gene regulation and PsaR-mediated gene
      regulation are required for full virulence in the establishment of pneumonia.
      Neither PcpA nor PsaR was found to be required for colonization of the
      nasopharynx in a carriage model. This is the first demonstration of Mn2+ acting
      as a signal for the expression of virulence factors within different host sites.

PMID- 16428767
TI  - Tumor necrosis factor alpha and gamma interferon, but not hemorrhage or pathogen
      burden, dictate levels of protective fibrin deposition during infection.
AB  - While coagulation often causes pathology during infectious disease, we recently
      demonstrated that fibrin, a product of the coagulation pathway, performs a
      critical protective function during acute toxoplasmosis (L. L. Johnson, K. N.
      Berggren, F. M. Szaba, W. Chen, and S. T. Smiley, J. Exp. Med. 197:801-806,
      2003). Here, we investigate the mechanisms regulating the formation of this
      protective fibrin. Through comparisons of Toxoplasma-infected wild-type and
      cytokine-deficient mice we dissociate, for the first time, the relative fibrin
      regulating capacities of pathogen products, host cytokines, and infection
      stimulated hemorrhage. Remarkably, neither the pathogen burden nor hemorrhage is
      a primary regulator of fibrin levels. Rather, two type 1 cytokines exert dominant
      and counterregulatory roles: tumor necrosis factor alpha (TNF-alpha), acting via
      the type 1 TNF-alpha receptor, promotes fibrin deposition, while gamma interferon
      (IFN-gamma), acting via STAT1 and IFN-gamma receptors expressed on radioresistant
      cells, suppresses fibrin deposition. These findings have important clinical
      implications, as they establish that cytokines known to regulate pathological
      coagulation also dictate levels of protective fibrin deposition. We present a
      novel model depicting mechanisms by which the immune system can destroy infected
      tissue while independently restraining hemorrhage and promoting tissue repair
      through the deliberate deposition of protective fibrin.

PMID- 16428768
TI  - Identification of a Naegleria fowleri membrane protein reactive with anti-human
      CD59 antibody.
AB  - Naegleria fowleri, the causative agent of primary amebic meningoencephalitis, is
      resistant to complement lysis. The presence of a complement regulatory protein on
      the surface of N. fowleri was investigated. Southern blot and Northern blot
      analyses demonstrated hybridization of a radiolabeled cDNA probe for CD59 to
      genomic DNA and RNA, respectively, from pathogenic N. fowleri. An 18-kDa
      immunoreactive protein was detected on the membrane of N. fowleri by Western
      immunoblot and immunofluorescence analyses with monoclonal antibodies for human
      CD59. Complement component C9 immunoprecipitated with the N. fowleri "CD59-like"
      protein from amebae incubated with normal human serum. In contrast, a gene or
      protein similar to CD59 was not detected in nonpathogenic, complement-sensitive
      N. gruberi amebae. Collectively, our studies suggest that a protein reactive with
      antibodies to human CD59 is present on the surface of N. fowleri amebae and may
      play a role in resistance to lysis by cytolytic proteins.

PMID- 16428769
TI  - Pathogenesis of B-cell superantigen-induced immune complex-mediated inflammation.
AB  - Staphylococcal protein A (SpA) is representative of a new class of antigens, the
      B-cell superantigens (SAgs). These antigens bind to the Fab regions of
      immunoglobulin molecules outside their complementarity-determining regions. SpA,
      the best-studied B-cell SAg, reacts with the Fabs of most VH3+ immunoglobulins,
      which are expressed on 30 to 60% of human peripheral B cells. Therefore, B-cell
      SAgs like SpA have great potential to elicit inflammatory responses in vivo. We
      previously reported that the interaction of SpA with VH3+ immunoglobulin
      molecules leads to activation of the complement cascade and produces a histologic
      pattern of inflammation in the skin of a rabbit indicative of immune complex
      injury. To elucidate the cellular and molecular events contributing to this type
      of unconventional immune complex-mediated inflammation, we established a mouse
      peritoneal Arthus reaction model. Mice treated intravenously with human
      polyclonal immunoglobulin G (IgG), followed by intraperitoneal injection of SpA,
      showed neutrophil influx into the peritoneal cavity with peak numbers appearing
      at 8 h. This inflammatory reaction was dependent on the interaction of SpA with
      VH3+ IgG. Mast cells, FcgammaRIII, complement components, and tumor necrosis
      factor alpha play obligatory roles, and the reaction is associated with the local
      release of the CXC chemokines macrophage inflammatory protein 2 and KC. The data
      provide further compelling evidence for the induction of immune complex-mediated
      injury by a B-cell SAg and highlight important factors contributing to the
      pathogenesis of this novel type of inflammatory reaction.

PMID- 16428770
TI  - Identification of proteins differentially expressed in human monocytes exposed to
      Porphyromonas gingivalis and its purified components by high-throughput
      immunoblotting.
AB  - To characterize the roles of Porphyromonas gingivalis and its components in
      disease processes, we investigated the cytokine profiles induced by live P.
      gingivalis, its lipopolysaccharide (LPS), and its major fimbrial protein,
      fimbrillin (FimA). A cytokine antibody array revealed that human monocyte-derived
      macrophages were induced to produce chemokines (e.g., monocyte chemoattractant
      protein 1, macrophage inflammatory protein 1beta [MIP-1beta], and MIP-3alpha) as
      early as 1 h after exposure to P. gingivalis, with production declining after 24
      h of exposure. As expected, an extensive repertoire of inflammatory mediators
      increased subsequent to infection, most predominantly tumor necrosis factor alpha
      (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-10, and granulocyte
      macrophage colony-stimulating factor. The induction of cytokines by P. gingivalis
      was not triggered simply by bacterial cell surface components, since purified P.
      gingivalis LPS and FimA induced similar patterns of cytokines, while the pattern
      of cytokines induced by live P. gingivalis was significantly different,
      indicating that the host defense system senses live bacteria differently than it
      does the cell surface components LPS and FimA. To further understand the
      mechanisms by which live P. gingivalis and its components exert their effects, we
      used a high-throughput immunoblot screening approach (Becton-Dickinson PowerBlot)
      to analyze intracellular proteins involved in P. gingivalis infection in human
      macrophages. Exposure of human macrophages to either live P. gingivalis, its LPS,
      or its FimA protein led to the up-regulation of 12, 8, and 10 proteins and the
      down-regulation of 15, 8, and 17 proteins, respectively. The expression of
      proteins involved in gene transcription (e.g., monocyte enhancer factor 2D
      [MEF2D], signal transducer and activator of transcription 1 [STAT1], STAT3,
      STAT6, and IL enhancer binding factors [ILF3]), of protein kinases (e.g., mitogen
      activated protein kinase 3 [MAPK3], MAP3K8, double-stranded RNA-activated protein
      kinase [PRKR], and MAP2K4), and of proteins involved in immune responses (e.g.,
      TNF super family member 6 [TNFSF6] and interferon-induced protein with
      tetratricopeptide repeat 4 [IFIT4]), apoptosis (e.g., genes associated with
      retinoid interferon-induced mortality 19 [GRIM19]), and other fundamental
      cellular processes (e.g., clathrin heavy-chain polypeptide, culreticulin, and Ras
      associated protein RAB27A) was found to be modulated differentially by P.
      gingivalis, LPS, and FimA. These differential changes are interpreted as
      preferential signal pathway activation in host immune/inflammatory responses to
      P. gingivalis infection.

PMID- 16428771
TI  - Cytokine production associated with periportal fibrosis during chronic
      schistosomiasis mansoni in humans.
AB  - Volunteers living in an area where schistosomiasis mansoni is endemic were
      subjected to ultrasound examination and classified into groups according to the
      levels of fibrosis diagnosed, namely, absence of indications of fibrosis (group
      0), incipient fibrosis (group 1), and moderate/severe fibrosis (group 2).
      Peripheral blood mononuclear cells (PBMC) collected from the volunteers were
      stimulated with soluble antigens from adult schistosomes or from schistosome
      eggs, and the production of the cytokines gamma interferon, tumor necrosis factor
      alpha, transforming growth factor beta (TGF-beta), interleukin-4 (IL-4), IL-10,
      and IL-13 was determined. Potential associations of the level of fibrosis with
      age, sex, intensity of infection, and cytokine production were investigated
      between the three groups. Univariate analysis identified associations of age
      (>50), gender (male), and absence of eggs/g of feces with moderate/severe
      fibrosis and an association of intensity of infection (>100 eggs) with incipient
      fibrosis. When cytokine production in PBMC cultures stimulated by soluble egg
      antigens was categorized as low or high, significant differences in the
      distribution of IL-13 levels were established between groups 0 and 2. No
      significant differences were detected between the groups in the cytokines
      produced by PBMC cultures stimulated with soluble antigens from adult
      schistosomes. When all variables were tested in multivariate analyses, only IL-13
      was strongly associated with fibrosis (odds ratio = 5.8; 95% confidence interval
      [CI] = 1.1 to 30.5). While high levels of TGF-beta appeared to be associated with
      protection against fibrosis, the strength of the association was low.

PMID- 16428772
TI  - Identification of amino acid residues involved in heme binding and hemoprotein
      utilization in the Porphyromonas gingivalis heme receptor HmuR.
AB  - We have previously identified and characterized a heme/hemoglobin receptor, HmuR,
      in Porphyromonas gingivalis. To analyze the conserved amino acid residues of HmuR
      that may be involved in hemin/hemoprotein binding and utilization, we constructed
      a series of P. gingivalis A7436 hmuR mutants with amino acid replacements and
      characterized the ability of these mutants to utilize hemin and hemoproteins.
      Site-directed mutagenesis was employed to introduce mutations H95A, H434A, H95A
      H434A, YRAP420-423YAAA, and NPDL442-445NAAA into HmuR in both P. gingivalis and
      Escherichia coli. Point mutations at H95 and H434 and in the NPDL motif of HmuR
      resulted in decreased binding to hemin, hemoglobin, and human serum albumin-hemin
      complex. Notably, mutations of these conserved sites and motifs led to reduced
      growth of P. gingivalis when human serum was used as the heme source. Analysis
      using a three-dimensional homology model of HmuR indicated that H95, H434, and
      the NPDL motif are present on apical or extracellular loops of HmuR, while the
      YRAP motif is present on the barrel wall. Taken together, these results support a
      role for H95, H434, and the NPDL motif of the P. gingivalis HmuR protein in heme
      binding and utilization of serum hemoproteins and the HmuR YRAP motif in serum
      hemoprotein utilization.

PMID- 16428773
TI  - Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary
      tuberculosis.
AB  - Although tuberculosis remains a substantial global threat, the mechanisms that
      enable mycobacterial persistence and replication within the human host are ill
      defined. This study represents the first genome-wide expression analysis of
      Mycobacterium tuberculosis from clinical lung samples, which has enabled the
      identification of M. tuberculosis genes actively expressed during pulmonary
      tuberculosis. To obtain optimal information from our DNA array analyses, we
      analyzed the differentially expressed genes within the context of computationally
      inferred protein networks. Protein networks were constructed using functional
      linkages established by the Rosetta stone, phylogenetic profile, conserved gene
      neighbor, and operon computational methods. This combined approach revealed that
      during pulmonary tuberculosis, M. tuberculosis actively transcribes a number of
      genes involved in active fortification and evasion from host defense systems.
      These genes may provide targets for novel intervention strategies.

PMID- 16428774
TI  - Polynucleotide phosphorylase negatively controls spv virulence gene expression in
      Salmonella enterica.
AB  - Mutational inactivation of the cold-shock-associated exoribonuclease
      polynucleotide phosphorylase (PNPase; encoded by the pnp gene) in Salmonella
      enterica serovar Typhimurium was previously shown to enable the bacteria to cause
      chronic infection and to affect the bacterial replication in BALB/c mice (M. O.
      Clements et al., Proc. Natl. Acad. Sci. USA 99:8784-8789, 2002). Here, we report
      that PNPase deficiency results in increased expression of Salmonella plasmid
      virulence (spv) genes under in vitro growth conditions that allow induction of
      spv expression. Furthermore, whole-genome microarray-based transcriptome analyses
      of bacteria growing inside murine macrophage-like J774.A.1 cells revealed six
      genes as being significantly up-regulated in the PNPase-deficient background,
      which included spvABC, rtcB, entC, and STM2236. Mutational inactivation of the
      spvR regulator diminished the increased expression of spv observed in the pnp
      mutant background, implying that PNPase acts upstream of or at the level of SpvR.
      Finally, competition experiments revealed that the growth advantage of the pnp
      mutant in BALB/c mice was dependent on spvR as well. Combined, our results
      support the idea that in S. enterica PNPase, apart from being a regulator of the
      cold shock response, also functions in tuning the expression of virulence genes
      and bacterial fitness during infection.

PMID- 16428776
TI  - Anthrax lethal toxin induces ketotifen-sensitive intradermal vascular leakage in
      certain inbred mice.
AB  - Bacillus anthracis lethal toxin (LT) is a bipartite toxin composed of protective
      antigen (PA) and lethal factor (LF). Injection of LT produces clinical signs
      characteristic of anthrax infection, including pleural edema and vascular
      collapse in various animal models. We utilized the classic Miles leakage assay to
      quantify vascular leakage in mice. LT injected intradermally induced leakage as
      early as 15 to 25 min in some inbred mouse strains, but not in others, whereas PA
      or LF individually did not induce leakage. A third component of anthrax toxin,
      edema factor, did not induce leakage alone or with PA. Leakage was quantified in
      eight mouse strains, and no correlation was found between sensitivity to
      intradermal leakage and sensitivity to the lethality of systemically administered
      LT. The leakage could be inhibited by ketotifen, an inhibitor of mast cell
      degranulation, but not by azelastine, a histamine receptor 1 antagonist, or by
      ketanserin, a serotonin 5-HT2A receptor antagonist. LT was cytotoxic to MC/9 mast
      cells (in vitro) by 7 h after toxin treatment but did not induce histamine
      release from these cells. Mast cell-deficient mice exhibited the leakage event
      and had no increased resistance to systemic LT. Human umbilical vein endothelial
      cells were resistant to LT over 12 h, with only 20% of cells succumbing by 24 h,
      suggesting that endothelial cell killing is not the cause of the rapid LT
      mediated leakage event. We describe here a ketotifen-sensitive vascular leakage
      event induced by LT which is the most rapid in vivo or in vitro LT-mediated
      effect reported to date.

PMID- 16428775
TI  - The established intimin receptor Tir and the putative eucaryotic intimin
      receptors nucleolin and beta1 integrin localize at or near the site of
      enterohemorrhagic Escherichia coli O157:H7 adherence to enterocytes in vivo.
AB  - For enterohemorrhagic Escherichia coli (EHEC) O157:H7 to adhere tightly to the
      intestinal epithelium and produce attach and efface (A/E) lesions, the organism
      must express the adhesin intimin and insert the bacterially encoded translocated
      intimin receptor Tir into the plasma membrane of the host enterocyte.
      Additionally, some reports based on tissue culture experiments indicate that
      intimin has affinity for the eucaryotic proteins nucleolin and beta1 integrin. To
      address the potential biological relevance of these eucaryotic proteins in the
      infection process in vivo, we sought to compare the proximity of Tir, nucleolin,
      and beta1 integrin to regions of EHEC O157:H7 attachment in intestinal sections
      from three different inoculated animals: piglets, neonatal calves, and mice.
      Piglets and neonatal calves were chosen because intimin-mediated adherence of
      EHEC O157:H7 and subsequent A/E lesion formation occur at high levels in these
      animals. Mice were selected because of their ease of manipulation but only after
      we first demonstrated that in competition with the normal mouse gut flora, an
      EHEC O157:H7 strain with a nonpolar deletion in the intimin gene was cleared
      faster than strains that produced wild-type or hybrid intimin. In all three
      animal species, we noted immunostained Tir beneath and stained nucleolin closely
      associated with adherent bacteria in intestinal sections. We also observed
      immunostained beta1 integrin clustered at locations of bacterial adherence in
      porcine and bovine tissue. These findings indicate that nucleolin and beta1
      integrin are present on the luminal surface of intestinal epithelia and are
      potentially accessible as receptors for intimin during EHEC O157:H7 infection.

PMID- 16428777
TI  - Glucosyltransferases of viridans group streptococci modulate interleukin-6 and
      adhesion molecule expression in endothelial cells and augment monocytic cell
      adherence.
AB  - Recruitment of monocytes plays important roles during vegetation formation and
      endocardial inflammation in the pathogenesis of infective endocarditis (IE).
      Bacterial antigens or modulins can activate endothelial cells through the
      expression of cytokines or adhesion molecules and modulate the recruitment of
      leukocytes. We hypothesized that glucosyltransferases (GTFs), modulins of
      viridans group streptococci, may act directly to up-regulate the expression of
      adhesion molecules and also interleukin-6 (IL-6) to augment monocyte attachment
      to endothelial cells. Using primary cultured human umbilical vein endothelial
      cells (HUVECs) as an in vitro model, we demonstrated that GTFs (in the cell-bound
      or free form) could specifically modulate the expression of IL-6, and also
      adhesion molecules, in a dose- and time-dependent manner. Results of inhibition
      assays suggested that enhanced expression of adhesion molecules was dependent on
      the activation of nuclear factor kappaB (NF-kappaB) and extracellular signal
      regulated kinase and that p38 mitogen-activated protein kinase pathways also
      contributed to the release of IL-6. Streptococcus-infected HUVECs or treatment
      with purified IL-6 plus soluble IL-6 receptor alpha enhanced the expression of
      ICAM-1 and the adherence of the monocytic cell line U937. These results suggest
      that streptococcal GTFs might play an important role in recruiting monocytic
      cells during inflammation in IE through induction of adhesion molecules and IL-6,
      a cytokine involved in transition from neutrophil to monocyte recruitment.

PMID- 16428779
TI  - Cathepsin B homologue at the interface between a parasitic nematode and its
      intermediate host.
AB  - Parelaphostrongylus tenuis is a parasitic nematode that causes a debilitating
      neurologic disease in many North American cervids and domestic livestock species.
      We produced a PCR-based cDNA library from infective larvae (L3) in order to
      identify molecules that mediate parasitism. A dominant 1,250-bp amplicon encoded
      a homologue of cathepsin B cysteine proteases. The sequence incorporated a C29G
      substitution in the putative active site. Antibodies generated against a
      recombinant form detected the native protein (PtCPR-1) in Western blot assays of
      L3, but not adult worm, extracts. Immunohistochemical methods revealed that PtCPR
      1 synthesis was restricted to larval stages within the snail intermediate host
      (Triodopsis sp.), beginning as early as 2 days postinfection (dpi) of snails. The
      protein was present in the intestine and luminal contents and was lost from
      larvae over time. Concurrent studies showed that larvae induced an immune
      response in snails beginning at 1 dpi. Layers of hemocytes encapsulated larvae
      immediately after infection, and granuloma-like structures formed around
      parasites in chronic infections. Loss of PtCPR-1 from L3 and its accumulation in
      host tissues coincided with degeneration of granuloma architecture 90 to 105 dpi.
      Fully developed L3 emerged from the snail at this time. Our data implicate PtCPR
      1 in larval development and possibly in the emergence of P. tenuis from the
      intermediate host. Emerged L3 survived desiccation and cold stress, suggesting
      that they could remain infectious in the environment. Molecules promoting
      emergence would facilitate dispersal of L3 and increase the likelihood of
      transmission to definitive hosts.

PMID- 16428778
TI  - Intranasal exposure to bacterial superantigens induces airway inflammation in HLA
      class II transgenic mice.
AB  - Staphylococcus aureus is widely prevalent in the nasopharynges of healthy
      individuals (carriers) but can also cause serious infections. S. aureus can
      elaborate a variety of superantigen exotoxins in "carrier" or "pathogenic"
      states. Streptococcus pyogenes can also colonize the nasopharynx and elaborate
      superantigens. Unlike the acute effects of superantigen exotoxins absorbed
      through the gut or vaginal mucosa, little is known regarding the pathogenesis of
      superantigens entering through the intranasal route. In the current study, we
      evaluated the local and systemic effects of staphylococcal enterotoxin B (SEB)
      and streptococcal pyrogenic exotoxin A (SPEA) delivered through the intranasal
      route. Superantigens were administered intranasally on multiple occasions, and
      experimental animals were sacrificed on day 8 for experimental analyses. SEB
      induced airway inflammation was more pronounced for HLA-DR3 transgenic mice than
      for BALB/c mice, consistent with bacterial superantigens binding more efficiently
      to human than murine major histocompatibility complex class II. The nature of the
      airway inflammation in HLA-DR3 mice was determined by the concentration of SEB
      applied intranasally. Low concentrations (20 ng) induced eosinophilic airway
      inflammation as well as eosinophil degranulation, whereas intranasal exposure to
      higher concentrations (2,000 ng) resulted in neutrophilic airway inflammation,
      permanent airway destruction, toxic shock, and mortality. SEB-induced
      eosinophilic inflammatory response was enhanced in signal transducer and
      activator of transcription (STAT)-4-deficient HLA-DQ8 transgenic mice with
      defective interleukin-12 signaling. Intranasal administration of SPEA induced
      airway inflammation and systemic immune activation in HLA-DQ8 transgenic mice. In
      conclusion, repeated chronic intranasal exposure to bacterial superantigens
      causes airway inflammation and systemic immune activation.

PMID- 16428780
TI  - Biogenesis of Leishmania major-harboring vacuoles in murine dendritic cells.
AB  - In mammalian hosts, Leishmania sp. parasites are obligatory intracellular
      organisms that invade macrophages and dendritic cells (DC), where they reside in
      endocytic organelles termed parasitophorous vacuoles (PV). Most of the present
      knowledge of the characteristics of PV harboring Leishmania sp. is derived from
      studies with infected macrophages. Since DC play a key role in host resistance to
      leishmaniasis, there is a need to understand the properties and biogenesis of PV
      in Leishmania sp.-infected DC. Therefore, we determined the acquisition of
      endosomal and lysosomal molecules by Leishmania major-containing compartments in
      DC at different maturation stages, using fluorescence labeling and confocal
      microscopy. The results show that newly formed phagosomes in DC rapidly develop
      into late endosomal compartments. However, the small GTPase Rab7, which regulates
      late fusion processes, was found only in PV of mature bone marrow-derived DC
      (BMDC); it was absent in immature BMDC, suggesting an arrest of their PV
      biogenesis at the stage of late endosomes. Indeed, fusion assays with endocytic
      tracers demonstrated that the fusion activity of L. major-harboring PV toward
      lysosomes is higher in mature BMDC than in immature BMDC. The inhibition of PV
      lysosome fusion in DC is dependent upon the viability and life cycle stage of the
      parasite, because live promastigotes blocked the fusion almost completely,
      whereas killed organisms and amastigotes induced a considerable level of fusion
      activity. The differences in the fusion competences of immature and mature DC may
      be relevant for their distinct functional activities in the uptake, transport,
      and presentation of parasite antigens.

PMID- 16428781
TI  - Analysis of antibodies directed against merozoite surface protein 1 of the human
      malaria parasite Plasmodium falciparum.
AB  - The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an
      essential component in the parasite's life cycle, is a primary candidate for a
      malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1
      processing products p83, p30, p38, and p42, derived from strain 3D7, were
      analyzed for the potential to inhibit in vitro erythrocyte invasion by the
      parasite and parasite growth. Our data show that (i) epitopes recognized by
      antibodies, which inhibit parasite replication, are distributed throughout the
      entire MSP-1 molecule; (ii) when combined, antibodies specific for different
      regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1
      antibodies interfere with erythrocyte invasion as well as with the
      intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP
      1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB
      1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with
      parasite multiplication at more than one level. Since the overall immunogenicity
      profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys
      immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from
      whom highly inhibiting antigen-specific antibodies were recovered, we consider
      the findings reported here to be relevant for the development of MSP-1-based
      vaccines against malaria.

PMID- 16428782
TI  - Intracellular gene expression profile of Listeria monocytogenes.
AB  - Listeria monocytogenes is a gram-positive, food-borne microorganism responsible
      for invasive infections with a high overall mortality. L. monocytogenes is among
      the very few microorganisms that can induce uptake into the host cell and
      subsequently enter the host cell cytosol by breaching the vacuolar membrane. We
      infected the murine macrophage cell line P388D1 with L. monocytogenes strain EGD
      e and examined the gene expression profile of L. monocytogenes inside the
      vacuolar and cytosolic environments of the host cell by using whole-genome
      microarray and mutant analyses. We found that approximately 17% of the total
      genome was mobilized to enable adaptation for intracellular growth.
      Intracellularly expressed genes showed responses typical of glucose limitation
      within bacteria, with a decrease in the amount of mRNA encoding enzymes in the
      central metabolism and a temporal induction of genes involved in alternative
      carbon-source utilization pathways and their regulation. Adaptive intracellular
      gene expression involved genes that are associated with virulence, the general
      stress response, cell division, and changes in cell wall structure and included
      many genes with unknown functions. A total of 41 genes were species specific,
      being absent from the genome of the nonpathogenic Listeria innocua CLIP 11262
      strain. We also detected 25 genes that were strain specific, i.e., absent from
      the genome of the previously sequenced L. monocytogenes F2365 serotype 4b strain,
      suggesting heterogeneity in the gene pool required for intracellular survival of
      L. monocytogenes in host cells. Overall, our study provides crucial insights into
      the strategy of intracellular survival and measures taken by L. monocytogenes to
      escape the host cell responses.

PMID- 16428783
TI  - Expression microarray and mouse virulence analysis of four conserved two
      component gene regulatory systems in group a streptococcus.
AB  - Group A streptococcus (GAS) is a gram-positive human bacterial pathogen that
      causes diseases ranging from relatively mild epithelial cell surface infections
      to life-threatening invasive episodes. Much is known about the extracellular
      molecules that contribute to host-pathogen interactions, but in contrast, far
      less information is available about regulatory genes that control the expression
      of individual or multiple GAS virulence factors. The eight GAS genomes that have
      been sequenced have 12 conserved two-component gene regulatory systems (TCSs),
      but only 3 of these 12 have been studied in detail. Using an allelic replacement
      strategy with a nonpolar cassette, we inactivated the response regulator of four
      TCSs that have only weak homology with TCS genes of known or inferred function in
      other bacteria. The mutant strains were analyzed by expression microarray
      analysis at four time points and tested in two mouse infection models. Each TCS
      influenced expression (directly or indirectly) of 12 to 41% of all chromosomal
      genes, as assessed by growth in Todd-Hewitt broth and a custom Affymetrix
      GeneChip. None of the isogenic mutant strains was significantly altered for mouse
      virulence based on intraperitoneal inoculation. Similarly, compared to the wild
      type strain, there was no significant difference in skin lesion size for three of
      the four mutants. In contrast, the DeltaM5005_Spy_0680 mutant strain produced
      significantly larger abscesses after subcutaneous inoculation into mice,
      consistent with a hypervirulence phenotype. The mutant strain had significantly
      higher in vitro expression of several proven and putative virulence genes,
      including scpA, encoding a peptidase that inactivates complement protein C5a.
      Together, the data provide new information about previously uncharacterized GAS
      TCSs.

PMID- 16428784
TI  - Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to
      fluconazole and virulence of Cryptococcus neoformans.
AB  - We have recently demonstrated that upregulation of the ATP binding cassette (ABC)
      transporter-encoding gene AFR1 in Cryptococcus neoformans is involved in the in
      vitro resistance to fluconazole of this yeast. In the present study, we
      investigated the role of AFR1 in the in vivo response to fluconazole in a mouse
      model of systemic cryptococcosis. Mice were infected with a wild-type fluconazole
      susceptible strain of C. neoformans, strain BPY22; an afr1 mutant, BPY444, which
      displayed hypersusceptibility to fluconazole in vitro; or an AFR1-overexpressing
      strain, BPY445, which exhibited in vitro resistance to the drug. In each of the
      three groups, infected animals were randomly assigned to fluconazole treatment or
      untreated-control subgroups. As expected, fluconazole prolonged survival and
      reduced fungal tissue burdens (compared with no treatment) in BPY22- and BPY444
      infected mice, whereas it had no significant effects in mice infected with
      BPY445. When the pathogenicities of these strains in mice were investigated,
      strain BPY445 was significantly more virulent than BPY22 following inhalational
      or intravenous inoculation, but mice infected with BPY444 survived significantly
      longer than BPY22-infected animals only when infection was acquired via the
      respiratory tract. In in vitro macrophage infection studies, strain BPY445 also
      displayed enhanced intracellular survival compared with strains BPY22 and BPY444,
      suggesting that its increased virulence may be due to its reduced vulnerability
      to the antimicrobial factors produced by phagocytic cells. These findings
      indicate that the upregulation of the AFR1 gene is an important factor in either
      determining the in vivo resistance to fluconazole or influencing the virulence of
      C. neoformans.

PMID- 16428785
TI  - Lipooligosaccharide structure contributes to multiple steps in the virulence of
      Neisseria meningitidis.
AB  - Lipooligosaccharide (LOS) of Neisseria meningitidis has been implicated in
      meningococcal interaction with host epithelial cells and is a major factor
      contributing to the human proinflammatory response to meningococci. LOS mutants
      of the encapsulated N. meningitidis serogroup B strain NMB were used to further
      determine the importance of the LOS structure in in vitro adherence and invasion
      of human pharyngeal epithelial cells by meningococci and to study pathogenicity
      in a mouse (CD46 transgenic) model of meningococcal disease. The wild-type strain
      [NeuNAc-Galbeta-GlcNAc-Galbeta-Glcbeta-Hep2 (GlcNAc, Glcalpha) 3-deoxy-D-manno-2
      octulosonic acid (KDO2)-lipid A; 1,4' bisphosphorylated], although poorly
      adherent, rapidly invaded an epithelial cell layer in vitro, survived and
      multiplied early in blood, reached the cerebrospinal fluid, and caused lethal
      disease in the mouse model. In contrast, the Hep2 (GlcNAc) KDO2-lipid A (pgm)
      mutant, which was highly adherent to cultured epithelial cells, caused
      significantly less bacteremia and mortality in the mouse model. The Hep2-KDO2
      lipid A (rfaK) mutant was shown to be moderately adherent and to cause levels of
      bacteremia and mortality similar to those caused by the wild-type strain in the
      mouse model. The KDO2-lipid A (gmhB) mutant, which lacks the heptose disaccharide
      in the inner core of LOS, avidly attached to epithelial cells but was otherwise
      avirulent. Disease development correlated with expression of specific LOS
      structures and was associated with lower adherence but rapid meningococcal
      passage to and survival in the bloodstream, induction of proinflammatory
      cytokines, and the crossing of the blood-brain barrier. Taken together, the
      results of this study further define the importance of the LOS structure as a
      virulence component involved in multiple steps in the pathogenesis of N.
      meningitidis.

PMID- 16428787
TI  - Reservoir competency of goats for the Ap-variant 1 strain of Anaplasma
      phagocytophilum.
AB  - Field-collected ticks were used to infect goats with either Ap-ha, a strain
      associated with human disease, or a variant strain, Ap-Variant 1, of Anaplasma
      phagocytophilum. Goats were shown to be competent as a reservoir for Ap-Variant
      1, and challenge and immunosuppression studies were used to further examine
      infection in the goat model.

PMID- 16428786
TI  - Exchange of lipooligosaccharide synthesis genes creates potential Guillain-Barre
      syndrome-inducible strains of Campylobacter jejuni.
AB  - Human ganglioside-like structures, such as GM1, found on some Campylobacter
      jejuni strains have been linked to inducing the Guillain-Barre Syndrome (GBS).
      This study shows that a C. jejuni strain without GM1-like molecules acquired
      large DNA fragments, including lipooligosaccharide synthesis genes, from a strain
      expressing GM1-like molecules and consequently transformed into a number of
      potential GBS-inducible transformants, which exhibited a high degree of genetic
      and phenotypic diversity.

PMID- 16428788
TI  - Pathogen-accelerated atherosclerosis occurs early after exposure and can be
      prevented via immunization.
AB  - Here we report on early inflammatory events associated with Porphyromonas
      gingivalis-accelerated atherosclerosis in apolipoprotein E knockout (ApoE-/-)
      mice. Animals challenged with P. gingivalis presented with increased macrophage
      infiltration, innate immune marker expression, and atheroma without elevated
      systemic inflammatory mediators. This early local inflammatory response was
      prevented in mice immunized with P. gingivalis. We conclude that localized up
      regulation of innate immune markers early after infection, rather than systemic
      inflammation, contributes to pathogen-accelerated atherosclerosis.

PMID- 16428790
TI  - Role of phase variation of type 1 fimbriae in a uropathogenic Escherichia coli
      cystitis isolate during urinary tract infection.
AB  - Type 1 fimbrial phase-locked mutants of uropathogenic Escherichia coli cystitis
      isolate F11 were used to assess the role of the invertible element during urinary
      tract infection. Compared to the wild type, the phase-locked off mutant was
      attenuated, and constitutive production of type 1 fimbriae by the phase-locked on
      mutant did not provide a competitive advantage.

PMID- 16428789
TI  - Calcium-regulated type III secretion of Yop proteins by an Escherichia coli hha
      mutant carrying a Yersinia pestis pCD1 virulence plasmid.
AB  - A series of four large deletions that removed a total of ca. 36 kb of DNA from
      the ca. 70-kb Yersinia pestis pCD1 virulence plasmid were constructed using
      lambda Red-mediated recombination. Escherichia coli hha deletion mutants carrying
      the virulence plasmid with the deletions expressed a functional calcium-regulated
      type III secretion system. The E. coli hha/pCD1 system should facilitate
      molecular studies of the type III secretion process.

PMID- 16428792
TI  - Salmonella enterica serovar Typhimurium ompS1 and ompS2 mutants are attenuated
      for virulence in mice.
AB  - Salmonella enterica serovar Typhimurium mutants with mutations in the ompS1 and
      ompS2 genes, which code for quiescent porins, were nevertheless highly attenuated
      for virulence in a mouse model, indicating a role in pathogenesis. Similarly, a
      strain with a mutation in the gene coding for LeuO, a positive regulator of
      ompS2, was also attenuated.

PMID- 16428791
TI  - A DltA mutant of Haemophilus ducreyi Is partially attenuated in its ability to
      cause pustules in human volunteers.
AB  - Haemophilus ducreyi produces two outer membrane proteins, called DltA (H. ducreyi
      lectin A) and DsrA (H. ducreyi serum resistance A), that contribute to the
      ability of the organism to evade complement-mediated serum killing. In contrast
      to their isogenic parent strain, 35000HP, the DsrA mutant FX517 exhibits 0%
      survival in 50% normal human serum and the DltA mutant FX533 exhibits 23%
      survival. Compared to 35000HP, FX517 does not cause pustule formation in human
      volunteers. To test whether DltA was required for virulence in humans, seven
      volunteers were experimentally infected with 35000HP and FX533. Four subjects
      were inoculated with fixed doses of 35000HP (101 CFU or 130 CFU) at three sites
      on one arm and escalating doses of FX533 (range, 46 CFU to 915 CFU) at three
      sites on the other arm. Pustules only developed at mutant-injected sites at doses
      nearly twofold higher than that of the parent, suggesting that FX533 was
      partially attenuated. Three subjects were inoculated with similar doses of the
      parent (67 CFU) and mutant (104 CFU) at three sites. Pustules formed at five of
      nine parent sites and one of nine mutant sites. Overall, the papule and pustule
      formation rates for 35000HP and FX533 were similar for the trial. However, for
      the five subjects who received similar doses of the parent and mutant, pustules
      developed at 7 of 15 sites (46.7%; 95% confidence interval [CI], 16.9% to 76.5%)
      inoculated with the parent and at 1 of 15 (6.7%; 95% CI, 0.1% to 18.4%) sites
      inoculated with the mutant (P = 0.043). We concluded that the DltA mutant was
      attenuated in its ability to cause disease at doses similar to that of the
      parent.

PMID- 16428793
TI  - Killed Candida albicans yeasts and hyphae inhibit gamma interferon release by
      murine natural killer cells.
AB  - Killed yeasts and hyphae of Candida albicans inhibit gamma interferon secretion
      by highly purified murine NK cells in response to the Toll-like receptor ligands
      lipopolysaccharide and zymosan. This effect, which is also observed in the
      presence of NK-activating cytokines (interleukin-2 [IL-2], IL-12, and IL-15), may
      represent a novel mechanism of immune evasion that contributes to the virulence
      of C. albicans.

PMID- 16428794
TI  - Human tumor necrosis factor is a chemoattractant for the parasite Entamoeba
      histolytica.
AB  - In an analysis of the molecular factors triggering amebiasis, we investigated the
      chemotaxis of Entamoeba histolytica toward tumor necrosis factor (TNF) in vitro,
      using quantitative imaging techniques. Our findings enabled us to propose a
      hitherto unknown role for TNF as a chemokinetic and chemoattractant agent for
      this parasite.

PMID- 16428795
TI  - Naturally elicited antibodies to glycosylphosphatidylinositols (GPIs) of
      Plasmodium falciparum require intact GPI structures for binding and are directed
      primarily against the conserved glycan moiety.
AB  - Immunization with a synthetic glycan corresponding to Plasmodium falciparum
      glycosylphosphatidylinositols (GPIs) has been proposed as a vaccination strategy
      against malaria. We investigated the structural requirements for binding of
      naturally elicited anti-GPI antibodies to parasite GPIs. The data show that anti
      GPI antibody binding requires intact GPI structures and that the antibodies are
      directed predominantly against GPIs with a conserved glycan structure with three
      mannoses and marginally against the terminal fourth mannose. The results provide
      valuable insight for exploiting GPIs for the development of malaria vaccines.

PMID- 16428796
TI  - Immune responses induced in cattle by vaccination with a recombinant adenovirus
      expressing Mycobacterial antigen 85A and Mycobacterium bovis BCG.
AB  - Cattle were vaccinated with an adenovirus expressing the mycobacterial antigen
      85A (rAd85A), with Mycobacterium bovis BCG followed by rAd85A heterologous
      boosting, or with rAd85A followed by BCG boosting. BCG/rAd85A resulted in the
      highest direct gamma interferon responses. Cultured enzyme-linked immunospot
      assay analysis demonstrated that memory responses were induced by all three
      protocols but were strongest after BCG/rAd85A and rAd85A/BCG vaccination.

PMID- 16428797
TI  - Induction of in vivo antipolysaccharide immunoglobulin responses to intact
      Streptococcus pneumoniae is more heavily dependent on Btk-mediated B-cell
      receptor signaling than antiprotein responses.
AB  - The relative role of Btk-dependent B-cell receptor (BCR) signaling in the
      induction of antipolysaccharide (anti-PS) and antiprotein immunoglobulin (Ig)
      responses to an intact extracellular bacterium in vivo is unknown. Btklow mice
      exhibit reduced BCR signaling but largely restore B-cell development. Btklow mice
      immunized with intact Streptococcus pneumoniae elicit reduced anti-PS but normal
      antiprotein Ig responses. Immunization of Btklow mice with PS-protein conjugate
      in saline results in an even more profound defect in the anti-PS but not
      antiprotein response, which is largely restored by use of a CpG-containing
      oligodeoxynucleotide as an adjuvant. These data demonstrate a greater dependence
      on Btk-mediated BCR signaling for physiologic anti-PS relative to antiprotein
      responses, as well as the existence of a compensatory Toll-like-receptor-mediated
      signaling pathway naturally triggered in response to intact bacterial pathogens.

PMID- 16428798
TI  - Macrophages isolated from chickens genetically resistant or susceptible to
      systemic salmonellosis show magnitudinal and temporal differential expression of
      cytokines and chemokines following Salmonella enterica challenge.
AB  - Macrophages from inbred chickens that are resistant to salmonellosis show greater
      and more rapid expression of proinflammatory chemokines and cytokines, including
      the key Th1-inducing cytokine interleukin-18, upon Salmonella challenge than
      those from susceptible birds. This suggests the possibility that salmonellosis
      resistant-line macrophages signal more effectively and rapidly and are more able
      to induce protective Th1 adaptive responses.

PMID- 16428799
TI  - Upregulation of immunoregulatory Src homology 2 molecule containing inositol
      phosphatase and mononuclear cell hyporesponsiveness in oral mucosa during chronic
      periodontitis.
AB  - Our group and others have shown in vitro that repeated exposure of human
      mononuclear cells (MNC) to lipopolysaccharide can induce endotoxin tolerance,
      evidenced by downregulation of TLR2 and TLR4 mRNA and surface protein; moreover,
      the ability of the MNC to secrete inflammatory cytokines is reduced. In situ
      studies performed on diseased and healthy gingiva suggest that a similar pattern
      of endotoxin tolerance occurs in human oral mucosa with chronic periodontitis
      (CP). We hypothesized that this represents a fundamental immunoregulatory
      mechanism to restore immune homeostasis and protect the host from further tissue
      damage. In the current study, we extend these published studies by providing
      evidence that Src homology 2 containing inositol phosphatase, an inhibitor of NF
      kappaB activation and a negative regulator of the immune response, is upregulated
      in the oral mucosa during CP compared to its level during gingival health. We
      have also isolated MNC from patients with CP and those with healthy gingiva and
      show that MNC from CP subjects have a reduced capacity to upregulate TLR2, TLR4,
      and interleukin-1beta in response to endotoxin. Thus, we provide more definitive
      evidence for a basic mechanism of immunoregulation in the oral mucosa.

PMID- 16428800
TI  - Development of a guinea pig immune response-related microarray and its use to
      define the host response following Mycobacterium bovis BCG vaccination.
AB  - Immune responses in the guinea pig model are understudied because of a lack of
      commercial reagents. We have developed a custom-made guinea pig oligonucleotide
      microarray (81 spots) and have examined the gene expression profile of
      splenocytes restimulated in vitro from Mycobacterium bovis BCG-vaccinated and
      naive animals. Eleven genes were significantly (P < 0.05) up-regulated following
      vaccination, indicating a Th1-type response. These results show that microarrays
      can be used to more fully define immune profiles of guinea pigs.

PMID- 16428801
TI  - Clearance of enteric Salmonella enterica serovar Typhimurium in chickens is
      independent of B-cell function.
AB  - Salmonella enterica serovar Typhimurium colonizes the gut of chickens and is
      cleared from the intestine within about 3 weeks. Infection induces high levels of
      specific antibody, but B cells do not play an essential role in clearance of
      primary infection or in the enhanced clearance after secondary challenge.

PMID- 16428802
TI  - A specific detection of GlcNAcbeta1-6Manalpha1 branches in N-linked glycoproteins
      based on the specificity of N-acetylglucosaminyltransferase VI.
AB  - Malignant transformation is often accompanied by an aberrant glycosylation
      profile of the cell surface-in particular, the production of GlcNAcbeta1
      6Manalpha1 branches in N-linked glycoproteins. To identify the target
      glycoproteins, we show a method using recombinant chicken N
      acetylglucosaminyltransferase VI (GnT VI) and radiolabeled uridine (5'
      )diphosphate-GlcNAc. The assay exploits the fact that GnT VI has a strict
      requirement for the GlcNAcbeta1-6Manalpha1 structure for activity, when a
      pyridylaminated free N-glycan is used as the acceptor substrate. Human asialo
      agalacto alpha1-acid glycoprotein (AGP), which is known to contain GlcNAcbeta1
      6Manalpha1 branches in its N-linked glycan chains, was radiolabeled when reacted
      with GnT VI, whereas human asialo-agalacto transferrin and bovine fetuin, neither
      of which contains a GlcNAcbeta1-6Manalpha1 structure were not, thus corroborating
      the specificity of the assay. Several proteins from human serum after
      pretreatment with sialidase and beta-galactosidase could be detected using the
      assay. One was identified as AGP from its mobility on SDS-PAGE, demonstrating the
      potential of this assay even with crude materials. Furthermore, this method could
      detect a protein that was also positively stained with leukoagglutinating
      phytohemagglutinin (L(4)-PHA) using glycoproteins prepared from WiDr human colon
      cancer cells. This method should provide a useful complement to the current
      method, which relies on the specificity of L(4)-PHA.

PMID- 16428803
TI  - Assembly of a polymeric chain of SUMO1 on human topoisomerase I in vitro.
AB  - Human (h) DNA topoisomerase I has been identified as a major SUMO1 target in
      camptothecin-treated cells. In response to TOP1-mediated DNA damage induced by
      camptothecin, multiple SUMO1 molecules are conjugated to the N-terminal domain of
      a single TOP1 molecule. To investigate the molecular mechanism of SUMO1
      conjugation to TOP1, an in vitro system using purified SAE1/2, Ubc9, SUMO1, and
      TOP1 peptides was developed. Consistent with results from in vivo studies,
      multiple SUMO1 molecules were found to be conjugated to the N-terminal domain of
      a single TOP1 molecule. Systematic analysis has identified a single major SUMO1
      conjugation site located between amino acid residues 110 and 125 that contains a
      single lysine residue at 117 (Lys-117). Using a short peptide spanning this
      region, we showed that a poly-SUMO1 chain was assembled in this peptide at Lys
      117. Interestingly, a Ubc9-poly-SUMO1 intermediate had accumulated to a high
      level when the sumoylation assay was performed in the absence of hTOP1 substrate,
      suggesting a possibility that the poly-SUMO1 chain is formed on Ubc9 first and
      then transferred en bloc onto hTOP1. This is the first definitive demonstration
      of the assembly of a poly-SUMO1 chain on protein substrate. These results offer
      new insight into hTOP1 polysumoylation in response to TOP1-mediated DNA damage
      and may have general implications in protein polysumoylation.

PMID- 16428804
TI  - Dynamics of arrestin-rhodopsin interactions: acidic phospholipids enable binding
      of arrestin to purified rhodopsin in detergent.
AB  - We report that acidic phospholipids can restore the binding of visual arrestin to
      purified rhodopsin solubilized in n-dodecyl-beta-d-maltopyranoside. We used this
      finding to investigate the interplay between arrestin binding and the status of
      the retinal chromophore ligand in the receptor binding pocket. Our results showed
      that arrestin can interact with the late photoproduct Meta III and convert it to
      a Meta II-like species. Interestingly in these mixed micelles, the release of
      retinal and arrestin was no longer directly coupled as it is in the native rod
      disk membrane. For example, up to approximately 50% of the retinal could be
      released even though arrestin remains bound to the receptor in a long lived
      complex. We anticipate that this new ability to study these proteins in a
      defined, purified system will facilitate further structural and dynamic studies
      of arrestin-rhodopsin interactions.

PMID- 16428805
TI  - Automatic extension of Gene Ontology with flexible identification of candidate
      terms.
AB  - MOTIVATION: Gene Ontology (GO) has been manually developed to provide a
      controlled vocabulary for gene product attributes. It continues to evolve with
      new concepts that are compiled mostly from existing concepts in a compositional
      way. If we consider the relatively slow growth rate of GO in the face of the fast
      accumulation of the biological data, it is much desirable to provide an automatic
      means for predicting new concepts from the existing ones. RESULTS: We present a
      novel method that predicts more detailed concepts by utilizing syntactic
      relations among the existing concepts. We propose a validation measure for the
      automatically predicted concepts by matching the concepts to biomedical articles.
      We also suggest how to find a suitable direction for the extension of a
      constantly growing ontology such as GO. AVAILABILITY:
      http://autogo.biopathway.org SUPPLEMENTARY INFORMATION: Supplementary materials
      are available at Bioinformatics online.

PMID- 16428806
TI  - The MGED Ontology: a resource for semantics-based description of microarray
      experiments.
AB  - MOTIVATION: The generation of large amounts of microarray data and the need to
      share these data bring challenges for both data management and annotation and
      highlights the need for standards. MIAME specifies the minimum information needed
      to describe a microarray experiment and the Microarray Gene Expression Object
      Model (MAGE-OM) and resulting MAGE-ML provide a mechanism to standardize data
      representation for data exchange, however a common terminology for data
      annotation is needed to support these standards. RESULTS: Here we describe the
      MGED Ontology (MO) developed by the Ontology Working Group of the Microarray Gene
      Expression Data (MGED) Society. The MO provides terms for annotating all aspects
      of a microarray experiment from the design of the experiment and array layout,
      through to the preparation of the biological sample and the protocols used to
      hybridize the RNA and analyze the data. The MO was developed to provide terms for
      annotating experiments in line with the MIAME guidelines, i.e. to provide the
      semantics to describe a microarray experiment according to the concepts specified
      in MIAME. The MO does not attempt to incorporate terms from existing ontologies,
      e.g. those that deal with anatomical parts or developmental stages terms, but
      provides a framework to reference terms in other ontologies and therefore
      facilitates the use of ontologies in microarray data annotation. AVAILABILITY:
      The MGED Ontology version.1.2.0 is available as a file in both DAML and OWL
      formats at http://mged.sourceforge.net/ontologies/index.php. Release notes and
      annotation examples are provided. The MO is also provided via the NCICB's
      Enterprise Vocabulary System
      (http://nciterms.nci.nih.gov/NCIBrowser/Dictionary.do). CONTACT:
      Stoeckrt@pcbi.upenn.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 16428807
TI  - Hip3 interacts with the HIRA proteins Hip1 and Slm9 and is required for
      transcriptional silencing and accurate chromosome segregation.
AB  - The fission yeast HIRA proteins Hip1 and Slm9 are members of an evolutionarily
      conserved family of histone chaperones that are implicated in nucleosome
      assembly. Here we have used single-step affinity purification and mass
      spectrometry to identify factors that interact with both Hip1 and Slm9. This
      analysis identified Hip3, a previously uncharacterized 187-kDa protein, with
      similarity to S. cerevisiae Hir3. Consistent with this, cells disrupted for hip3+
      exhibit a range of growth defects that are similar to those associated with loss
      of Hip1 and Slm9. These include temperature sensitivity, a cell cycle delay, and
      synthetic lethality with cdc25-22. Furthermore, genetic analysis also indicates
      that disruption of hip3+ is epistatic with mutation of hip1+ and slm9+. Mutation
      of hip3+ alleviates transcriptional silencing at several heterochromatic loci,
      including in the outer (otr) centromeric repeats, indicating that Hip3 is
      required for the integrity of pericentric heterochromatin. As a result, loss of
      Hip3 function leads to high levels of minichromosome loss and an increased
      frequency of lagging chromosomes during mitosis. Importantly, the function of
      Hip1, Slm9, and Hip3 is not restricted to constitutive heterochromatic loci,
      since these proteins also repress the expression of a number of genes, including
      the Tf2 retrotransposons.

PMID- 16428808
TI  - [Eating disorders in a health-psychology approach: model of pathogenic processing
      of cognitive information].
AB  - A new theoretical approach of cognitive information processing in eating
      disorders is introduced. It is based on the system theory with a view on health
      psychology. We are going to emphasize the deviations in the self-concept, the
      role of procedural memory in body image disturbance and the content of working
      memory supporting the appearance of cognitive dysfunctions in eating disorders.
      Despite the long-standing interest in eating disorders a coherent body of
      empirically supported knowledge that can be used to direct clinical practice, has
      yet to emerge. Although there are many possible causes of this limited progress,
      one important source of difficulty is that research completed to date has tended
      to be based on clinical models of psychopathology lacking a sound theoretical
      framework. The complex multidimensional nature of the model shows several
      possibilities of prevention and intervention in eating disorders.

PMID- 16428809
TI  - [Substance use among homeless and family deprived adolescents].
AB  - Substance use, such as alcohol and illicit drugs, among young people is a growing
      problem worldwide. Family deprived, "runaway" children are at higher risk of
      facing this problem. The authors sum up the factors driving to "runaway"
      attitudes and substance use. The long term harmful effect of substance use and
      its biological, psychological, and social consequences are also discussed. The
      patterns of substance use of homeless people and among adopted children, or young
      people living in child care centers in Hungary are also demonstrated.

PMID- 16428810
TI  - [Psychotherapy of trauma-related borderline pathology].
AB  - Borderline pathology originating from trauma is characterized by increasingly
      severe borderline and comorbid symptoms, poor psychosocial function, and poor
      prognosis in comparison with borderline patients who have never undergone such
      traumatic experiences. Instead of psychodynamic therapy, other forms of
      psychotherapy, such as cognitive-behavioral approaches are offered helping to
      stabilize the patient's life and improve his or her ways of coping with
      stressors. Trauma recovery depends on appropriate timing and careful preparation,
      where the patient first must learn to trust the therapist and gain some ego
      strength. Failure to be properly prepared can lead to the escalation of former
      self-destructive defenses once used against the trauma. Typical transference
      counter-transference dynamics can be conceptualized as episodes in a drama
      involving four principal characters: a victim, an abuser, an idealized rescuer,
      and a betrayer mother. Role enactments oscillate in various complementary
      pairings between patient and therapist during the course of therapy.

PMID- 16428811
TI  - [Learned equivalence in schizophrenia: novel method for the measurement of memory
      functions of the hippocampus and basal ganglia].
AB  - The purpose of the present study was to investigate basal ganglia (BG) and medial
      temporal lobe (MTL) dependent learning in patients with schizophrenia. Acquired
      equivalence is a phenomenon in which prior training to treat two stimuli as
      equivalent (if two stimuli are associated with the same response) increases
      generalization between them. The learning of stimulus-response pairs is related
      to the BG, whereas the MTL system participates in stimulus generalization. Forty
      three patients with DSM-IV schizophrenia and 28 matched healthy controls
      participated in the study. Volunteers received the acquired equivalence
      associative learning task (FISHES) during which associations between faces and
      pet fishes are learned. Results revealed that patients with schizophrenia showed
      a selective deficit on stimulus generalization, whereas stimulus-response
      learning was unaffected. The number of errors during stimulus-response learning
      correlated with the daily chlorpromazine-equivalent dose of antipsychotics. In
      conclusion, patients with schizophrenia showed deficits during MTL-dependent
      learning, but not during BG-dependent learning. High-dose first generation
      antipsychotics may disrupt BG-dependent learning by blocking dopaminergic
      neurotransmission in the nigro-striatal system.

PMID- 16428812
TI  - [The prevalence of suicide ideas and their psychosocial backgrounds among
      physicians].
AB  - AIMS: A growing body of evidence in the literature suggests that the prevalence
      of psychiatric morbidity including suicide is high among physicians. Suicidal
      ideas are the most important predictors of suicides and suicide attempts. The
      prevalence of suicidal ideas is higher among physicians compared to the general
      population. Our goal was to search the factors of suicidal ideas among Hungarian
      physicians on basis of nationwide representative survey, helping to elaborate
      prevention programs. METHODS: Data were collected from 298 female and 109 male
      physicians using questionnaires. 1,754 white-collar workers from a representative
      survey (Hungarostudy 2002) served as controls. Statistical analysis examined
      background factors of suicidal thoughts. RESULTS: We found that the prevalence of
      suicidal ideas among both female (20,3%) and male physicians (12,1%) was
      significantly higher than that in the respective control groups (12,3% - 7,6%).
      Female physicians also exhibited significantly higher prevalence of suicidal
      ideas (p=0.0058 es OR=1,901). Suicidal ideas were associated with work-related
      stress. Correlation analyses confirmed a significant relationship between high
      prevalence of suicidal ideas and long working hours (>8 hours), severe anxiety
      and work-related stress, and role conflict. Further examination of the background
      factors of suicidal thoughts may help to elaborate more effective health
      prevention and conflict-dealing methods.

PMID- 16428813
TI  - [Do the antidepressants increase suicide risk?].

PMID- 16428814
TI  - [Letter to the Editor. Psychiatric terminology].

PMID- 16428815
TI  - Molecular mechanism of allergy-related gene regulation and hematopoietic cell
      development by transcription factors.
AB  - Transcriptional regulation for the genes encoding alpha- and beta-chains of the
      high-affinity receptor for IgE (FcepsilonRI) have been analyzed in mast cells and
      regulatory mechanisms are beginning to be elucidated. Transcription factors GATA
      1 and PU.1 cooperatively transactivate the alpha-chain gene, and three
      transcription factors, GATA-1, Oct-1, and MZF-1, are involved in regulation of
      beta-chain gene expression. No single nucleotide polymorphisms (SNPs) that are
      functionally related to the allergic diseases have been identified in coding
      regions of the alpha- and beta-chain genes in a definitive way. However, recent
      studies on SNPs in the promoter regions have revealed that these genes are
      probable candidates for new types of allergy-related genes whose transcription
      levels are affected by transcription factors which discriminate SNPs in the
      promoters. Another interesting finding on transcription factors functioning in
      mast cells is that the expression level of PU.1 determines cell fate between mast
      cells and monocytes.

PMID- 16428816
TI  - The physiological role of the ribulose monophosphate pathway in bacteria and
      archaea.
AB  - 3-Hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI) are
      the key enzymes of the ribulose monophosphate pathway. This pathway, which was
      originally found in methylotrophic bacteria, is now recognized as a widespread
      prokaryotic pathway involved in formaldehyde fixation and detoxification. Recent
      progress, involving biochemical and genetic approaches in elucidating the
      physiological functions of HPS and PHI in methylotrophic as well as non
      methylotrophic bacteria are described in this review. HPS and PHI orthologs are
      also found in a variety of archaeal strains. Some archaeal HPS orthologs are
      fused with other genes to form single ORF (e.g., the hps-phi gene of Pyrococcus
      spp. and the faeB-hpsB gene of Methanosarcina spp). These fused gene products
      exhibit functions corresponding to the individual enzyme activities, and are more
      efficient than equivalent systems made up of discrete enzymes. Recently, a novel
      metabolic function for HPS and PHI has been proposed in which these enzymes
      catalyze the reverse reaction for the biosynthesis of pentose phosphate in some
      archaeal strains. Thus the enzyme system plays a different role in bacteria and
      archaea by catalyzing the forward and reverse reactions respectively.

PMID- 16428817
TI  - Changes in composition and content of mycolic acids in glutamate-overproducing
      Corynebacterium glutamicum.
AB  - Overproduction of glutamate by Corynebacterium glutamicum is induced by biotin
      limitation or by the supplementation of specific detergents, sublethal amounts of
      penicillin, or cerulenin. But, it remains unclear why these different treatments,
      which have different sites of primary action, produce similar effects. In this
      study, it was found that the cellular content of mycolic acids--characteristic
      constituents of Corynebacterineae that are synthesized from fatty acids and form
      a cell surface layer--decreased under all conditions that induced glutamate
      overproduction. Furthermore, short mycolic acids increased under conditions of
      biotin limitation and cerulenin supplementation. These results suggest that
      different treatments produce the same effect that causes defects in the mycolic
      acid layer. This is perhaps one of the key factors in overproduction of glutamate
      by C. glutamicum.

PMID- 16428818
TI  - Anti-diabetic effect of alkaline-reduced water on OLETF rats.
AB  - Alkalin-reduced water (ARW) is known to exert several anti-cancer effects, as
      well as to scavenge reactive oxygen species (ROS) and reduce blood-glucose
      levels. This study was performed in order to determine the effects of ARW on the
      control of spontaneous diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF)
      rats. We assigned 16 male OLETF rats (4 wk) to two groups: an experimental group,
      which was given ARW, and a control group, which received laboratory tap water.
      From week 6 to 32, the body weight, lipid composition, and glucose levels in the
      blood of the rats were measured. The glucose levels of both groups tended to
      increase. However, the ARW group's glucose levels were significantly lower than
      those of the control group after 12 weeks (p<0.05). The total cholesterol and
      triglyceride levels in the ARW group were found to be significantly lower than
      those of the control group during the experimental period. These results suggest
      that ARW spurred the growth of OLETF rats during the growth stage, and that long
      term ingestion of ARW resulted in a reduction in the levels of glucose,
      triglycerides, and total cholesterol in the blood.

PMID- 16428819
TI  - Antitumor activities of O-sulfonated derivatives of (1-->3)-alpha-D-glucan from
      different Lentinus edodes.
AB  - Four water-insoluble (1-->3)-alpha-D-glucans, coded L-II1, L-II2, L-II3 and L
      II4, with different molecular weights were isolated from four kinds of fruiting
      bodies of Lentinus Edodes. The four alpha-D-glucans were O-sulfonated to obtain
      derivatives (SL-II) having degrees of substitution (DS) from 0.9 to 2.1
      respectively. The structure of the samples was analyzed by infrared spectra,
      elemental analysis, and 13C NMR. The weight-average molecular weight (Mw), radii
      of gyration (<s2>z1/2) and intrinsic viscosity ([eta]) of the native alpha-D
      glucans and O-sulfonated derivatives were measured by size-exclusion
      chromatography combined with laser light scattering (SEC-LLS), LLS, and
      viscometry in 0.2 M aqueous NaCl and in dimethyl sulfoxide (DMSO) containing 0.25
      M LiCl at 25 degrees C respectively. The Mw values of the O-sulfonated
      derivatives were much lower than those of the native alpha-D-glucans. The
      experimental results indicate that the O-sulfonated derivatives are water-soluble
      and exist as an expanded flexible chain in aqueous solution owing to
      intramolecular hydrogen bonding or interaction between charge groups. The in vivo
      and in vitro antitumor activities of the native alpha-D-glucans and their O
      sulfonated derivatives against solid tumor Sarcoma 180 cells were evaluated and
      compared. Interestingly, all of the O-sulfonated derivatives exhibited higher
      antitumor activities than those of the native glucans. The results reveal that
      the effect of O-sulfonation of the alpha-D-glucan on the improvement of their
      antitumor activities was considerable.

PMID- 16428820
TI  - Effect of estrogens on the interferon-gamma producing cell population of mouse
      splenocytes.
AB  - We examined the effect of 17beta-estradiol (E2) on the cytokine production by
      mouse splenocytes. The production of interferon-gamma (IFN-gamma) was enhanced by
      E2 stimulation. E2 increased the number of cells expressing IFN-gamma and the IFN
      gamma mRNA expression level in the cells. There were low- and high-level cells
      expressing IFN-gamma in the population. The natural killer (NK) cells and NKT
      cells were the low-level cells expressing IFN-gamma, and the number of these
      cells was increased by E2 stimulation. In addition, it was suggested that the
      enhancing effect of IFN-gamma production by E2 was mediated through estrogen
      receptor (ER) alpha, and ERbeta agonist stimulated IFN-gamma production. ERs are
      expressed on plasma membrane as well as in nucleus. The ligand specific to plasma
      membrane-associated ER (mER) enhanced the IFN-gamma production. In conclusion,
      our results indicated that E2 up-regulated the IFN-gamma production by mediating
      ERalpha, ERbeta and mERs.

PMID- 16428821
TI  - Simultaneous determination of residual veterinary drugs in bovine, porcine, and
      chicken muscle using liquid chromatography coupled with electrospray ionization
      tandem mass spectrometry.
AB  - A simple and rapid method using liquid chromatography coupled with electrospray
      ionization tandem mass spectrometry (LC/MS/MS) for the simultaneous determination
      of 130 veterinary drugs and their metabolites in bovine, porcine, and chicken
      muscle was developed. The drugs (1 to 10 ng/g, in muscle) were extracted from
      bovine, porcine, or chicken muscles with acetonitrile-methanol (95:5, v/v), and
      the extracts were delipidated with n-hexane saturated with acetonitrile. The
      extracts were evaporated, dissolved with methanol, analyzed by liquid
      chromatography with gradient elution on a C18 column, and determined by
      electrospray ionization tandem mass spectrometry. The detection limits ranged
      from 0.03 to 3 ng/g. The quantitation limits ranged from 0.1 to 10 ng/g. One
      hundred eleven, 122, and 123 drugs from bovine, porcine, and chicken muscle
      respectively showed recoveries between 70 and 110%.

PMID- 16428822
TI  - Interfacial behavior of fatty-acylated sericin prepared by lipase-catalyzed solid
      phase synthesis.
AB  - Fatty-acylated sericin {1:0.7 molar ratio of sericin (Mr 18,700) to oleic acid}
      was prepared by lipase-catalyzed solid-phase synthesis in n-hexane containing
      oleic acid to endow sericin with interfacial properties. Acylation with oleic
      acid was confirmed by 1H-NMR. The fatty-acylated sericin exhibited superior
      emulsifying activity index and emulsion stability in the presence of 0-0.5 M
      NaCl, in a temperature range of 30-80 degrees C and pH range of 2-7, as compared
      with the control sericin. The fatty-acylated sericin (1:0.4 molar ratio) prepared
      by using low-molecular-weight sericin (Mr 5,000) also exhibited superior
      emulsifying properties. The affinity of the fatty-acylated sericin to a
      hydrophobic surface as evaluated by a biomolecular interaction analyzer was about
      twice as much as that of the control sericin. The fatty-acylated sericin showed
      retarded water vaporization, similar to the control sericin, indicating good
      retention of moistness, and was adsorbed four times as much to defatted wool with
      little desorption as compared with the control sericin.

PMID- 16428823
TI  - Contribution of the net charge to the regulatory effects of amino acids and
      epsilon-poly(L-lysine) on the gelatinization behavior of potato starch granules.
AB  - The effects of lysine (Lys), monosodium glutamate (GluNa), glycine, alanine and
      epsilon-poly(L-lysine) (PL) with different degrees of polymerization on the
      gelatinization behavior of potato starch granules were investigated by DSC,
      viscosity and swelling measurements, microscopic observation, and measurement of
      the retained amino acid amount to clarify the contribution of the net charge to
      their regulatory effects on the gelatinization behavior. The amino acids and PL
      each contributed to an increase in the gelatinization temperature, and a decrease
      in the peak viscosity and swelling. These effects strongly depended on the
      absolute value of their net charge. The disappearance of a negative or positive
      net charge by adjusting the pH value weakened the contribution. The swelling
      index and size of the potato starch granules changed according to replacement of
      the swelling medium. The amino acids and PL were easily retained by the swollen
      potato starch granules according to replacement of the outer solution of the
      starch granules.

PMID- 16428824
TI  - Reducing effect of feeding powdered scallop shell on the body fat mass of rats.
AB  - The lipolytic effect of powdered scallop shells was estimated in vitro and in
      vivo. The scallop shells consisted of 98% calcium carbonate and 2% organic
      compounds, the extracted organic components promoted lipolysis in 3T3-L1
      adipocyte cells. Male Wistar rats were fed on an experimental diet containing
      either the scallop shell powder or calcium carbonate (control) for 28 d. Feeding
      the scallop shell powder resulted in a decrease in body weight and in the weight
      of white adipose tissue. While the organ weights of the liver, kidney, testis,
      pancreas, and spleen, and of the brown adipose tissue relative to the body weight
      were no different between the scallop shell powder diet and control diet, the
      white adipose tissue weight relative to the body weight significantly decreased
      in the rats fed on the scallop shell powder. The glycerol concentration in the
      serum increased in the rats fed on the scallop shell powder, suggesting that this
      promoted lipolysis in the adipose tissue. These results show that the organic
      components in the scallop shells induced the decrease in weight of the adipose
      tissue due to the promotion of lipolysis.

PMID- 16428825
TI  - Analysis of tissue-specific expression of human type II collagen cDNA driven by
      different sizes of the upstream region of the beta-casein promoter.
AB  - To investigate the ability of 1.8 kb or 3.1 kb bovine beta-casein promoter
      sequences for the expression regulation of transgene in vivo, transgenic mice
      were produced with human type II collagen gene fused to 1.8 kb and 3.1 kb of
      bovine beta-casein promoter by DNA microinjection. Five and three transgenic
      founder mice were produced using transgene constructs with 1.8 kb and 3.1 kb of
      bovine beta-casein promoters respectively. Founder mice were outbred with the
      wild type to produce F1 and F2 progenies. Total RNAs were extracted from four
      tissues (mammary gland, liver, kidney, and muscle) of female F1 transgenic mice
      of each transgenic line following parturition. RT-PCR and Northern blot analysis
      revealed that the expression level of transgene was variable among the transgenic
      lines, but transgenic mice containing 1.8 kb of promoter sequences exhibited more
      leaky expression of transgene in other tissues compared to those with 3.1 kb
      promoter. Moreover, Western blot analysis of transgenic mouse milk showed that
      human type II collagen proteins secreted into the milk of lactating transgenic
      mice contained 1.8 kb and 3.1 kb of bovine beta-casein promoter. These results
      suggest that promoter sequences of 3.1 kb bovine beta-casein gene can be used for
      induction of mammary gland-specific expression of transgenes in transgenic
      animals.

PMID- 16428826
TI  - Production of (R)-3-amino-3-phenylpropionic acid and (S)-3-amino-3
      phenylpropionic acid from (R,S)-N-acetyl-3-amino-3-phenylpropionic acid using
      microorganisms having enantiomer-specific amidohydrolyzing activity.
AB  - (R)-3-Amino-3-phenylpropionic acid ((R)-beta-Phe) and (S)-3-amino-3
      phenylpropionic acid ((S)-beta-Phe) are key compounds on account of their use as
      intermediates in synthesizing pharmaceuticals. Enantiomerically pure non-natural
      amino acids are generally prepared by enzymatic resolution of the racemic N
      acetyl form, but despite the intense efforts this method could not be used for
      preparing enantiomerically pure beta-Phe, because the effective enzyme had not
      been found. Therefore, screening for microorganisms capable of amidohydrolyzing
      (R,S)-N-acetyl-3-amino-3-phenylpropionic acid ((R,S)-N-Ac-beta-Phe) in an
      enantiomer-specific manner was performed. A microorganism having (R)-enantiomer
      specific amidohydrolyzing activity and another having both (R)-enantiomer- and
      (S)-enantiomer-specific amidohydrolyzing activities were obtained from soil
      samples. Using 16S rDNA analysis, the former organism was identified as
      Variovorax sp., and the latter as Burkholderia sp. Using these organisms,
      enantiomerically pure (R)-beta-Phe (>99.5% ee) and (S)-beta-Phe (>99.5% ee) with
      a high molar conversion yield (67%-96%) were obtained from the racemic substrate.

PMID- 16428827
TI  - Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug
      induced amnesia.
AB  - The choline acetyltransferase (ChAT) activator, which enhances cholinergic
      transmission via an augmentation of the enzymatic production of acetylcholine
      (ACh), is an important factor in the treatment of Alzheimer's disease (AD).
      Methanolic extracts from Pueraria thunbergiana exhibited an activation effect
      (46%) on ChAT in vitro. Via the sequential isolation of Pueraria thunbergiana,
      the active component was ultimately identified as daidzein (4',7-dihydroxy
      isoflavone). In order to investigate the effects of daidzein from Pueraria
      thunbergiana on scopolamine-induced impairments of learning and memory, we
      conducted a series of in vivo tests. Administration of daidzein (4.5 mg/kg body
      weight) to mice was shown significantly to reverse scopolamine-induced amnesia,
      according to the results of a Y-maze test. Injections of scopolamine into mice
      resulted in impaired performance on Y-maze tests (a 37% decreases in alternation
      behavior). By way of contrast, mice treated with daidzein prior to the
      scopolamine injections were noticeably protected from this performance impairment
      (an approximately 12%-21% decrease in alternation behavior). These results
      indicate that daidzein might play a role in acetylcholine biosynthesis as a ChAT
      activator, and that it also ameliorates scopolamine-induced amnesia.

PMID- 16428828
TI  - Consumption of pork-liver protein hydrolysate reduces body fat in Otsuka Long
      Evans Tokushima Fatty rats by suppressing hepatic lipogenesis.
AB  - This study was performed to examine the effect of consumption of pork-liver
      protein hydrolysate (PLH) on body fat accumulation in Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats as a non-insulin-dependent diabetes mellitus model and in Long
      Evans Tokushima Otsuka (LETO) rats as a control. Male 20-week-old OLETF and LETO
      rats were pair-fed either PLH or casein containing diet for 14 weeks. In the
      OLETF rats, dietary PLH significantly reduced the growth and weight of fat pad
      including perirenal and epididymal adipose tissues. Consumption of PLH markedly
      suppressed hepatic activities of lipogenesis enzymes such as glucose-6-phosphate
      dehydrogenase and fatty acid synthase and slightly elevated fecal excretion of
      total fat. In the LETO rats, growth and adipose tissue weight were unaffected by
      dietary treatment. The results suggest that PLH is a novel ingredient suppressing
      body fat in genetically obese rats by reducing lipogenesis.

PMID- 16428829
TI  - Construction of a positive selection marker by a lethal gene with the amber stop
      codon(s) regulator.
AB  - A novel positive selection marker for Escherichia coli transformation was
      developed. The marker consisted of a DNA fragment encoding the C-terminal
      ribonuclease domain (CRD) of colicin E3 (colE3) and one or more amber stop codons
      between the initiation codon and the E3-CRD coding sequence. The toxicity of the
      marker was controlled by the suppressor activity the host cells possessed. This
      allowed both effective selection and propagation of the vector possessing the
      maker by selecting appropriate hosts from among those widely distributed: sup+
      strains for selection and sup0 strains for propagation respectively. The insert
      DNA fragment was introduced onto the vector by replacing the marker DNA. The
      transformants harboring the vector with an insert grew, but those without an
      insert were effectively removed by the killing activity of E3-CRD encoded on the
      marker DNA. The marker was also successfully applied to lambda phage display
      vector.

PMID- 16428830
TI  - Purification and characterization of an intracellular chymotrypsin-like serine
      protease from Thermoplasma volcanium.
AB  - An intracellular serine protease produced by Thermoplasma (Tp.) volcanium was
      purified using a combination of ammonium sulfate fractionation, ion exchange, and
      alpha-casein agarose affinity chromatography. This enzyme exhibited the highest
      activity and stability at pH 7.0, and at 50 degrees C. The purifed enzyme
      hydrolyzed synthetic peptides preferentially at the carboxy terminus of
      phenylalanine or leucine and was almost completely inhibited by PMSF, TPCK, and
      chymostatin, similarly to a chymotrypsin-like serine protease. Kinetic analysis
      of the Tp. volcanium protease reaction performed using N-succinyl-L-phenylalanine
      p-nitroanilide as substrate revealed a Km value of 2.2 mM and a Vmax value of
      0.045 micromol(-1) ml(-1) min(-1). Peptide hydrolyzing activity was enhanced by
      >2-fold in the presence of Ca2+ and Mg2+ at 2-12 mM concentration. The serine
      protease is a monomer with a molecular weight of 42 kDa as estimated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and zymogram activity
      staining.

PMID- 16428832
TI  - Ovalbumin-related gene Y protein bears carbohydrate chains of the ovomucoid type.
AB  - We have recently established the monoclonal antibodies (mAbs) specific to the
      major food allergen, ovomucoid, as mAb 7D, recognizing the carbohydrate moiety of
      ovomucoid, and mAb 6H, the peptide moiety (Biosci. Biothechnol. Biochem., 68,
      2490-2497, (2004)). Using these mAbs, we found commercially available ovalbumin
      preparations contaminated with a considerable amount of ovomucoid together with
      other glycoproteins. To examine the contaminants, egg white was subjected to
      cation-exchange chromatography. An unidentified protein was found in egg white
      that reacted with mAb 7D but not with mAb 6H, having a molecular size of about 52
      kDa and a blocked N-terminus. Two internal amino acid sequences of the fragments
      obtained after a lysyl endopeptidase and a hydroxylamine treatment revealed the
      protein to be ovalbumin Y (ovalbumin-related gene Y protein). We conclude that
      ovalbumin Y is a unique chimeric glycoprotein having an amino acid sequence
      similar to that of ovalbumin, but having a carbohydrate moiety similar to that of
      ovomucoid.

PMID- 16428831
TI  - Identification and analysis of Ku70 and Ku80 homologs in the koji molds
      Aspergillus sojae and Aspergillus oryzae.
AB  - Ku genes play a key role in the non-homologous end-joining pathway. We have
      identified Ku70 and Ku80 homologs in the koji molds Aspergillus sojae and
      Aspergillus oryzae, and have constructed the disruption mutants of Ku70, Ku80,
      and Ku70-80 to characterize the phenotypic change in these mutants. Neither Ku70-
      nor Ku80-disrupted strains show hypersensitivity to the DNA damaging agents
      methylmethane sulfonate (MMS) and phleomycin. Moreover, undesirable phenotypes,
      such as poor growth or repressed conidiospore formation, were not observed in the
      Ku-disrupted A. sojae and A. oryzae.

PMID- 16428833
TI  - Water-soluble complexes formed by natural polyphenols and bovine serum albumin:
      evidence from gel electrophoresis.
AB  - The formation of water-soluble complexes from combinations of various polyphenols
      and bovine serum albumin (BSA) was analyzed by gel electrophoresis. Sodium
      dodecylsulfate (SDS) and native polyacrylamide gel electrophoretic (PAGE)
      analyses clearly showed complexes formed from BSA with oenothein B, corilagin,
      (+)-catechin, procyanidin B3, and gallic acid derivatives; however, it was
      difficult to distinguish between the complexes containing a single BSA molecule
      and the BSA molecule itself by using size-exclusion chromatography (SEC).
      Combining SDS and native PAGE analyses showed instability in the macromolecular
      complexes formed from pentagalloylglucose (PGG) and BSA. Research also revealed
      that the oxidation of (-)-epigallocatechin gallate (EGCG) contributed to the
      formation of more stable macromolecular complexes from EGCG and BSA.

PMID- 16428834
TI  - Induction of a ribotoxic stress response that stimulates stress-activated protein
      kinases by 13-deoxytedanolide, an antitumor marine macrolide.
AB  - 13-Deoxytedanolide is a structurally unique macrolide with strong antitumor
      activity isolated from a marine sponge. Recently, we showed that 13
      deoxytedanolide bound to the large subunit of the yeast ribosome and inhibited
      polypeptide elongation in vitro, but the mechanism by which it exerts antitumor
      activity is still unknown. Here we show that 13-deoxytedanolide strongly induces
      plasminogen activator inhibitor 1 (PAI-1) promoter-derived gene expression. 13
      Deoxytedanolide, unlike TGF-beta, did not cause apparent nuclear translocation of
      Smad2/3, but it relocalized the temperature-sensitive mutant of mouse p53
      (p53Val153) from the cytoplasm to the nucleus at a nonpermissive temperature,
      suggesting that 13-deoxytedanolide inhibits protein synthesis. Indeed, the drug
      inhibited in vivo protein synthesis at low nanomolar concentrations and strongly
      activated stress-activated protein kinases such as p38 mitogen-activated protein
      kinase and Jun NH2-terminal protein kinase (JNK). Anisomycin, a well-known
      inducer of ribotoxic stress that activates both p38 and JNK, also activated PAI-1
      gene expression, while other protein synthesis inhibitors that do not activate
      the kinases failed to do so. PAI-1 gene expression by 13-deoxytedanolide and
      anisomycin was blocked by SB202190, a specific inhibitor of p38, and SP600125, an
      inhibitor of both p38 and JNK. 13-Deoxytedanolide and anisomycin caused
      activation of apoptosis signal-regulating kinase 1, MKK3/MKK6, and SEK1/MKK4, the
      regulatory kinases upstream of p38 and JNK. These results suggest that 13
      deoxytedanolide, like anisomycin, triggers a ribotoxic stress response that
      activates stress-activated protein kinase cascades, thereby inducing PAI-1 gene
      expression and apoptosis.

PMID- 16428835
TI  - Changes in caffeic acid derivatives in sweet potato (Ipomoea batatas L.) during
      cooking and processing.
AB  - There was an obvious decrease in caffeic acid derivatives during the boiling of
      cube-shaped blocks of sweet potatoes. They also decreased in a mixture of freeze
      dried sweet-potato powder and water maintained at room temperature. Ascorbic acid
      prevented the decrease, supporting the occurrence of an enzyme reaction with
      polyphenol oxidase (PPO). 5-O-Caffeoylquinic acid (5-CQA, "3-O-caffeoylquinic
      acid" as a trivial name) and 3,5-di-O-caffeoylquinic acid (3,5-CQA), major
      phenolic compounds of sweet potato, did not change when they were separately
      heated in boiling water. When the mixture of powdered sweet potato and water was
      heated at 100 degrees C, there was only a negligible decrease in the total amount
      of phenolic compounds, and portions of 5-CQA and 3,5-CQA were found to be
      isomerized to 3-CQA, 4-CQA, 3,4-CQA, and 4,5-CQA. The content and composition of
      the phenolic compounds in sweet potatoes differed between fresh and long-stored
      ones, as did their response to heating.

PMID- 16428836
TI  - Flavonoid composition of fruit tissues of citrus species.
AB  - An HPLC analysis was performed on the concentrations of flavonoids in 42 species
      and cultivars of the Citrus genus and those of two Fortunella and one Poncirus
      species according to the classification system established by Tanaka. The
      composition of 8 flavanones and 9 flavone/ols for these species was determined in
      the albedo, flavedo, segment epidermis and juice vesicle tissues, and those in
      the fruit and peel tissues were calculated from the composition data of the
      tissues. A principal component analysis showed that such neohesperidosyl
      flavonoids as neoeriocitrin, naringin, neohesperidin, and rhoifolin had large
      factor loading values in the first principal component for each tissue. The
      flavonoid composition of citrus fruits was approximately the same within each
      section of Tanaka's system, except for the species in the Aurantium section and
      those with a peculiar flavonoid composition such as Bergamot (C. bergamia), Marsh
      grapefruit (C. paradisi), Sour orange (C. aurantium), and Shunkokan (C.
      shunkokan). The Aurantium section included both naringin-rich and hesperidin-rich
      species.

PMID- 16428837
TI  - DPPH radical scavenging reaction of hydroxy- and methoxychalcones.
AB  - The DPPH radical scavenging activity of 2',4',6'-trihydroxy- and 2'-hydroxy-4',6'
      dimethoxychalcones carrying a 2,3- and 3,4-dihydroxylated, and 3,4,5
      trihydroxylated B-ring was evaluated in alcoholic and non-alcoholic solvents. All
      test compounds scavenged more than two equivalent of radicals by a possible
      conversion to the corresponding B-ring quinones and in most cases subsequently
      underwent cyclization to aurones and flavanones, these being identified in the
      reaction solutions by an in situ NMR analysis. Interestingly, the reaction
      between 2',3,4-trihydroxy-4',6'-dimethoxychalcone and the DPPH radical was
      significantly affected by the solvent used, which might be accounted for by the
      difference in readiness for cyclization to an aurone.

PMID- 16428839
TI  - Phylogenetic and morphological diversity of Bacteroidales members associated with
      the gut wall of termites.
AB  - The microbial community adherent directly or indirectly to the gut wall of
      termites is distinct from that of the other habitats in the gut. The bacterial
      16S rRNA genes were identified from the fractionated gut walls of two termite
      species, Hodotermopsis sjoestedti and Neotermes koshunensis, and compared with
      those previously identified from Reticulitermes speratus. Surprisingly, the
      bacterial constituents were almost entirely different among the termites at the
      phylotype level (the criterion of the phylotype was >97% nucleotide identity).
      Bacteria in the order Bacteroidales, which were commonly abundant symbionts on
      gut walls, were phylogenetically analyzed. They were dispersed in a number of
      clusters formed by phylotypes from the guts of various termites. In situ
      hybridization with probes specific for some phylotypes and a phylogenetic cluster
      detected the cells of several Bacteroidales members with a significant variety of
      cell morphology in the gut wall fractions, which reflects the phylogenetic
      diversity of this order.

PMID- 16428838
TI  - Activation of murine peritoneal macrophages by water-soluble extracts of
      Bursaphelenchus xylophilus, a pine wood nematode.
AB  - In our previous study, water-soluble extracts from Bursaphelenchus xylophilus (B.
      xylophilus), a pine wood nematode, were shown to enhance interleukin (IL)-4 plus
      lipopolysaccharide-induced polyclonal immunoglobulin (Ig) E production in vitro
      in mice and to increase serum levels of an antigen-nonspecific IgE in vivo. Here
      we examined whether the nematode extracts stimulate immunofunctions of murine
      peritoneal macrophages. In both resident and inflammatory macrophages, Fcgamma
      receptor-mediated phagocytosis was markedly activated by B. xylophilus extracts,
      while non-specific phagocytosis was not. The enhancement of specific phagocytosis
      was accompanied by an increase in the formation of IgG-Fcgamma receptor rosettes.
      B. xylophilus extracts also stimulated IL-1beta production in both types of
      macrophages, and enhanced NO production and mRNA expression of inflammatory
      cytokines in inflammatory macrophages. These results indicate that the extracts
      of B. xylophilus contain an activating substance(s) for immunofunctions in
      macrophages, besides an enhancing factor for polyclonal IgE production.

PMID- 16428840
TI  - Effect of Bombyx mori chitinase against Japanese pine sawyer (Monochamus
      alternatus) adults as a biopesticide.
AB  - Bombyx mori chitinase (Bm-CHI), with a molecular mass of 75 kDa, was investigated
      on the possibility that it can serve as a biocontrol agent against the adult
      Japanese pine sawyer (JPS), Monochamus alternatus (Coleoptera: Cerambycidae).
      Oral ingestion of purified chitinase at concentrations of 3 microM (11.25
      microg/50 microl) and 0.3 micoM (1.125 microg/50 microl) caused high mortality in
      JPS, a significant decrease in bark consumption, and, only in high concentration,
      a slight reduction of body weight. Fluorescence assays indicated that peritrophic
      membrane (PM) chitin is degraded by the action of orally ingested Bm-CHI at 3
      microM concentration only. Scanning electron micrographs clearly indicated that
      the beetles that ingested Bm-CHI of the same high concentration had their PM
      perforated and disrupted, but ultrastructural studies showed that the ingested
      chitinase did not affect the midgut epithelium. These findings open up the
      possibility of using insect chitinase as a biopesticidal enzyme. It should have
      agronomic potential for insect control.

PMID- 16428841
TI  - A simple method with liquid chromatography/tandem mass spectrometry for the
      determination of the six trichothecene mycotoxins in rice medium.
AB  - A selective and speedy LC-MS/MS method was developed to determine six
      trichothecene mycotoxins (nivalenol, deoxynivalenol, fusarenon X, 15
      acetyldeoxynivalenol, 3-acetyldeoxynivalenol, and T-2 toxin) in rice medium where
      Fusarium graminearum were cultivated for in vitro tests. The analytes were
      extracted from the rice medium with acetonitrile/water (85/15, v/v), and diluted
      with acetonitrile/water (5/95, v/v) in order to minimize the effects of matrices.
      Diluted solutions were analyzed by LC-MS/MS with electrospray ionization (ESI)
      interface in negative or positive ion mode and the multiple reaction monitoring
      mode. Recovery rates were 76-106% with a spiked level at 1-6 microg/kg of
      mycotoxins that corresponded to the limit of quantitation. The method was applied
      to study the time courses of trichothecene production and the biomass of fungi by
      three Fusarium graminearum strains. Three strains have different mycotoxin
      biosynthesis pathways, wFg14 and 03E-1 were DON producer, and 03N-1 was NIV
      producer.

PMID- 16428842
TI  - An enzyme-linked immunosorbent assay (ELISA) to determine the specificity of the
      sugar-binding protein NgcE, a component of the ABC transporter for N
      acetylglucosamine in Streptomyces olivaceoviridis.
AB  - The ATP-binding cassette (ABC) transporter Ngc for N-acetylglucosamine (GlcNAc)
      of the chitin-degrader Streptomyces olivaceoviridis comprises the solute-binding
      protein NgcE, which has highest affinity for GlcNAc and N,N'-diacetylchitobiose
      {(GlcNAc)2} and reduced affinity for longer chitooligomers. NgcE was used to
      develop a generally applicable enzyme-linked immunosorbent assay (ELISA) system.
      As a prerequisite, the reducing end of (GlcNAc)2 was coupled with the ethylamino
      group of 2-(4-aminophenyl)ethylamine. The resulting conjugate was linked with
      amino groups of bovine serum albumin (BSA) to gain the neoglycoprotein BSA-APEA
      (GlcNAc)2, which was fixed to wells in microtitre-plates. The NgcE protein was
      shown to bind efficiently to the immobilized BSA-APEA-(GlcNAc)2. In competition
      assays, the affinity of NgcE was 1,000-fold higher for GlcNAc and (GlcNAc)2 than
      for (GlcNAc)3 and (GlcNAc)4. These results are consistent with those previously
      obtained by surface plasmon resonance. Since the ELISA method can be performed
      very rapidly at low cost, it should be an efficient general tool to determine the
      affinity of a ligand to its cognate solute-binding protein.

PMID- 16428843
TI  - Mutation of a conserved tryptophan in the chitin-binding cleft of Serratia
      marcescens chitinase A enhances transglycosylation.
AB  - Family 18 chitinases have the signature peptide DGXDXDXE forming the fourth beta
      strand in the (beta/alpha)8-barrel of their catalytic domain. The carboxyl-end
      glutamic acid, E315 in Serratia marcescens chitinase A, serves as the acid/base
      during chitin hydrolysis, and the side-chain of the preceding aspartic acid,
      D313, helps to position correctly the N-acetyl moiety of the glycosyl sugar
      undergoing hydrolysis. Chitin substrates are bound within a long cleft across the
      top of the barrel, whose floor consists of aromatic residues that hydrophobically
      stack with every other GlcNAc. Alanine substitution of the conserved Trp167 at
      the -3 subsite in Serratia marcescens chitinase A enhanced transglycosylation.
      Higher oligosaccharides were formed from both chitin tetra- and pentasaccharide,
      and the only hydrolytic product from chitin trisaccharide was the disaccharide.
      Greater retention of the glycosyl fragment at the active site of the -3 mutant of
      Serratia marcescens chitinase A might favor transglycosylation due to a
      stabilized conformation of its D313.

PMID- 16428844
TI  - Purification and characterization of a novel isozyme of chitinase from Bombyx
      mori.
AB  - 75-kDa chitinase, which showed potential as a biocontrol agent against Japanese
      pine sawyer, was characterized after purification from the integument of the
      fifth instar larvae of Bombyx mori by chromatography on diethylaminoethyl (DEAE)
      Toyoperal 650 (M), hydroxylapatite, and Fractogel EMD DEAE 650 (M) columns. The
      optimum pH was 6.0 toward N-acetylchitopentaose (GlcNAc5) and 10 toward
      glycolchitin. The optimum temperature was 60 degrees C toward GlcNAc5 and 25
      degrees C toward glycolchitn. The enzyme was stable at pH 7-10 and below 40
      degrees C. Kinetic analysis and reaction-pattern analysis using glycolchitin and
      N-acetylchitooligosacchraides as substrates indicated that 75-kDa chitinase is an
      endo- or random-type hydrolytic enzyme to produce the beta anomeric product and
      that it prefers the longer N-acetylchitooligosaccharides, suggesting, together
      with the N-terminal amino acid sequence, that the 75-kDa chitinase belongs to
      family 18 of glycosyl hydrolases.

PMID- 16428845
TI  - Bacteriostatic activities of monoacyl sugar alcohols against thermophilic
      sporeformers.
AB  - The bacteriostatic activities of monoacyl sugar alcohols with different acyl
      chains and hydrophilic heads were examined against some thermophilic
      sporeformers. Monomyristoyl erythritol and xylitol efficaciously suppressed their
      spore development. The number and orientation of the hydroxyl groups also played
      important roles in this activity, and monomyristoyl xylitol exhibited the highest
      activity among the monomyristoyl sugar alcohols.

PMID- 16428846
TI  - Inhibition of PSII in atrazine-tolerant tobacco cells by barbatic acid, a lichen
      derived depside.
AB  - In atrazine-tolerant tobacco cells with Ser to Thr mutation at the 264th amino
      acid of PsbA polypeptide in photosystem II (PSII), electron trannsport around the
      secondary quinone acceptor (Q(B)) site was inhibited to a greater extent by
      barbatic acid than in wild-type cells. Further characterization suggests similar
      mode of action of barbatic acid and phenyl-type herbicides.

PMID- 16428848
TI  - Ktr-mediated potassium transport, a major pathway for potassium uptake, is
      coupled to a proton gradient across the membrane in Synechocystis sp. PCC 6803.
AB  - Synechocystis sp. PCC 6803 contains a Ktr system and a putative ATP-dependent Kdp
      system for potassium uptake. We report here that the Kdp system plays only a
      minor role in potassium uptake under salt and non-stress conditions, unlike the
      role it plays in Escherichia coli. In Synechocystis, Ktr-mediated potassium
      transport is dependent on the proton gradient across the membrane.

PMID- 16428847
TI  - Identification, cloning, and expression of the Scytalidium acidophilum XYL1 gene
      encoding for an acidophilic xylanase.
AB  - We cloned XYL1, a Scytalidium acidophilum gene encoding for an acidophilic family
      11 xylanase. The XYL1p protein was expressed in Pichia pastoris using the
      pPICZalphaA expression plasmid. The secreted protein was purified by TAXI
      affinity column chromatography. The purified XYL1p showed an optimum activity at
      pH 3.2 and 56 degrees C. The Michaelis-Menten constants were determined.

PMID- 16428849
TI  - Improved isotopic deuterium labeling at the diastereotopic methyl group of
      leucine: a synthetic route to (4S)- and (4R)-[5-2H1]leucine.
AB  - Two isotopomers of deuterium-labeled leucine in the diastereotopic methyl group
      were synthesized from inexpensively available (R)- and (S)-citronellol in a more
      convenient way than by previous methods.

PMID- 16428850
TI  - Effects of combined administration of quercetin, rutin, and extract of white
      radish sprout rich in kaempferol glycosides on the metabolism in rats.
AB  - Quercetin, rutin, the extract of white radish sprout rich in kaempferol
      glycosides, and their combination were intragastrically administered to Wistar
      rats to investigate the interactive metabolism of these flavonoids. The combined
      administration of these flavonoids changed the concentrations of the metabolites
      in plasma as compared with the concentrations after the administration of a
      single compound.

PMID- 16428851
TI  - Identification of sn-glycerol-1-phosphate dehydrogenase activity from genomic
      information on a hyperthermophilic archaeon, Sulfolobus tokodaii strain 7.
AB  - sn-Glycerol-1-phosphate dehydrogenase is responsible for the formation of sn
      glycerol-1-phosphate, the backbone of membrane phospholipids of Archaea. This
      activity had never been detected in cell-free extract of Sulfolobus sp. Here we
      report the detection of this activity on the thermostable ST0344 protein of
      Sulfolobus tokodaii expressed in Escherichia coli, which was predicted from
      genomic information on S. tokodaii. This is another line of evidence for the
      general mechanism of sn-glycerol-1-phosphate formation by the enzyme.

PMID- 16428852
TI  - Effect of dietary green tea catechin preparation on oxidative stress parameters
      in large intestinal mucosa of rats.
AB  - Intake of green tea catechin (GTC) for 4 weeks was found to elevate vitamin E
      level in the mucosa of the rat large intestine. Iron-induced lipid peroxidation
      of the mucosal homogenate was suppressed by intake of GTC in rats fed
      monounsaturated fatty acid (MUFA), indicating that the protective effect of
      dietary GTC on mucosal oxidative stress is enhanced by combination with a MUFA
      rich diet.

PMID- 16428853
TI  - Reduced expression of perchloric acid-soluble protein after partial hepatectomy
      in rats.
AB  - We examined the expression of perchloric acid-soluble protein (PSP) during liver
      regeneration after partial hepatectomy (PH) in rats. Liver regeneration was
      almost complete at 7-d after PH. Expression of PSP protein and mRNA decreased and
      then gradually increased during liver regeneration. An immunohistochemical study
      showed that PSP is distributed in cytosol and nuclei in normal liver, but
      localization in the nuclei was not be recognized in the regenerated liver.

PMID- 16428854
TI  - Effect of chronic administration of fruit extract (Citrus unshiu Marc.) on
      glucose tolerance in GK rats, a model of type 2 diabetes.
AB  - Recent epidemiological studies have demonstrated that high dietary consumption of
      fruit and vegetables results in lower risks of diabetes. In this study, we
      investigated the effects of chronic administration of fruit extract (Citrus
      unshiu Marc.) on glucose tolerance in GK rats, a model of type 2 diabetes. After
      10 weeks administration of the fruit extract, intraperitoneal glucose tolerance
      tests revealed significant decrements of blood glucose levels after glucose
      loading. Our findings further support an advantageous association of fruit
      consumption with diabetes.

PMID- 16428855
TI  - Characterization of cold- and high-pressure-active polygalacturonases from a deep
      sea yeast, Cryptococcus liquefaciens strain N6.
AB  - A deep-sea yeast, Cryptococcus liquefaciens strain N6, produces two
      polygalacturonases, p36 and p40 (N6-PGases). These N6-PGases were highly active
      at 0-10 degrees C in comparison to a PGase from Aspergillus japonicus. The
      hydrolytic activity of these N6-PGases remained almost unchanged up to a
      hydrostatic pressure of 100 MPa at 24 degrees C with a very small activation
      volume of -1.1 ml/mol. At 10 degrees C, however, the activation volume increased
      to 3.3 or 5.4 ml/mol (p36 and p40, respectively), suggesting that the enzyme
      substrate complexes can expand at their transition states. We speculate that such
      a volume expansion upon forming the enzyme-substrate complexes contributes to
      decreasing the activation energy for hydrolysis. This can account for the high
      activity of N6-PGases at low-temperature.

PMID- 16428856
TI  - Atomic force microscopic observation of Escherichia coli ribosomes in solution.
AB  - Ribosomes of Escherichia coli were visualized in buffer solution by atomic force
      microscopy (AFM). A series of time-dependent AFM images showed that ribosomes
      spontaneously adsorb on mica. Although ribosomes observed in air are forced to
      flatten on the surface, the height of ribosomal particles obtained under a
      physiological buffer solution is 21.8+/-0.5 nm, which is consistent with the
      ideal diameter. We succeeded in observing single ribosomes in a near-native
      condition.

PMID- 16428857
TI  - Synthesis of quinolactacide via an acyl migration reaction and dehydrogenation
      with manganese dioxide, and its insecticidal activities.
AB  - Quinolactacide isolated from Penicillium citrinum F 1539 was synthesized and
      evaluated for its insecticidal activities. The key steps of the total synthesis
      were an acyl migration reaction of the enol ester intermediate and
      dehydrogenation of tetrahydroquinolactacide with manganese dioxide. The
      synthesized quinolactacide showed 100% and 42% mortality against the green peach
      aphid (Myzus persicae) and diamondback moth (Plutella xylostella) at 500 ppm,
      respectively.

PMID- 16428858
TI  - Hydroxylation of testosterone by bacterial cytochromes P450 using the Escherichia
      coli expression system.
AB  - Two hundred thirteen cytochrome P450 (P450) genes were collected from bacteria
      and expressed based on an Escherichia coli expression system to test their
      hydroxylation ability to testosterone. Twenty-four P450s stereoselectively
      monohydroxylated testosterone at the 2alpha-, 2beta-, 6beta-, 7beta-, 11beta-,
      12beta-, 15beta-, 16alpha-, and 17-positions (17-hydroxylation yields 17
      ketoproduct). The hydroxylation site usage of the P450s is not the same as that
      of human P450s, while the 2alpha-, 2beta-, 6beta-, 11beta-, 15beta-, 16alpha-,
      and 17-hydroxylation are reactions common to both human and bacterial P450s. Most
      of the testosterone hydroxylation catalyzed by bacterial P450s is on the beta
      face.

PMID- 16428859
TI  - The establishment of a HeLa cell demonstrating rapid mitogen-activated protein
      kinase phosphorylation in response to 1alpha,25-dihydroxyvitamin D3 by stable
      transfection of a chick skeletal muscle cDNA library.
AB  - 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] phosphorylates the extracellular
      signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase
      (MAPK) family, within 30 sec in primary cultured chick skeletal muscle cells.
      MAPK of HeLa cell lines, which had been stably transfected with a cDNA library
      derived from mRNA of chick skeletal muscle cells, was also rapidly phosphorylated
      by 1,25-(OH)2D3. These cell lines have the potential to be a good tool for
      further investigation of rapid non-genomic mechanism activated by 1,25-(OH)2D3.

PMID- 16428860
TI  - Phosphorylation of RanGAP1 stabilizes its interaction with Ran and RanBP1.
AB  - Ran is a nuclear Ras-like GTPase that is required for various nuclear events
      including the bi-directional transport of proteins and ribonucleoproteins through
      the nuclear pore complex, spindle formation, and reassembly of the nuclear
      envelope. One of the key regulators of Ran is RanGAP1, a Ran specific GTPase
      activating protein. The question of whether a mechanism exists for controlling
      nucleocytoplasmic transport through the regulation of RanGAP1 activity continues
      to be debated. Here we show that RanGAP1 is phosphorylated in vivo and in vitro.
      Serine-358 (358S) was identified as the major phosphorylation site, by MALDI-TOF
      MS spectrometry. Site directed mutagenesis at this position abolished the
      phosphorylation. Experiments using purified recombinant kinase and specific
      inhibitors such as DRB and apigenin strongly suggest that casein kinase II (CK2)
      is the responsible kinase. Although the phosphorylation of 358S of RanGAP1 did
      not significantly alter its GAP activity, the phosphorylated wild type RanGAP1,
      but not a mutant harboring a mutation at the phosphorylation site 358S,
      efficiently formed a stable ternary complex with Ran and RanBP1 in vivo,
      suggesting that the 358S phosphorylation of RanGAP1 affects the Ran system.

PMID- 16428861
TI  - Molecular dissection of internalization of Porphyromonas gingivalis by cells
      using fluorescent beads coated with bacterial membrane vesicle.
AB  - Porphyromonas gingivalis is one of the causative agents of adult periodontitis,
      and has been reported to be internalized by nonphagocytic epithelial cells.
      However, the mechanism for the internalization remains unclear. In the present
      study, we addressed this issue using fluorescent beads coated with bacterial
      membrane vesicles (MVs) that retain surface components of P. gingivalis. We
      established an assay system in which we could easily quantify the bead
      internalization to cells. MVs-coated beads were internalized by HeLa cells in
      kinetics similar to that of living bacteria. The internalization depended on
      dynamin but not clathrin. The beads were internalized through the actin-mediated
      pathway that is controlled by phosphatidylinositol (PI) 3-kinase. The dynamics of
      microtubule assembly and disassembly was also required. Further, the treatment of
      cells with cholesterol-binding reagents significantly inhibited bead
      internalization, and the internalized beads were apparently colocalized with
      ganglioside GM1 and caveolin-1, which suggest the involvement of the lipid raft
      in the process. These results suggest that P. gingivalis accomplishes its
      internalization utilizing membrane lipid raft and cytoskeletal functions of the
      target cells.

PMID- 16428862
TI  - Experimental evidence for the influence of cumulus-oocyte-complexes on sperm
      release from the porcine oviductal sperm reservoir.
AB  - In the pig, a temporal relationship is suggested between sperm release from the
      sperm reservoir (SR) and ovulation, but the mechanism(s) is still under
      discussion. In two experiments, the influence of transferred ova on the release
      of SR-spermatozoa at ovulation and the effect of supplementation with non
      sulfated glycosaminoglycan hyaluronan (HA) on embryo development and the number
      of accessory spermatozoa, respectively, were examined. PMSG/hCG primed
      ovectomized gilts that had previously received endoscopic low-dose insemination
      into the cranial uterine horn were used as an experimental model. After
      salpingectomy, tubal segments (ampulla, cranial, and caudal isthmus) were flushed
      and sperm numbers or respective accessory spermatozoa were counted. In Experiment
      1, the distribution of the sperm population was altered in the presence of
      cumulus-oocyte-complexes (COCs). A higher proportion of spermatozoa was found
      after transfer of COCs into one oviduct in the ampulla and cranial isthmus
      segments compared with the controls (17.5 vs. 4.9%, p<0.05). In Experiment 2, the
      quality of the transferred ova and treatment influenced the presence of accessory
      spermatozoa. Transfer of COCs together with HA increased (p<0.05) the number of
      accessory spermatozoa compared with the other treatment groups and was similar to
      those in the "undisturbed" controls. No modifications were obtained regarding
      mean blastomere numbers (2.6 +/- 0.2 to 3.1 +/- 0.2). In summary, this study was
      demonstrated that cumulus-oocyte-complexes may be involved in triggering sperm
      release from the pig oviductal SR and that HA might be related to sperm release.

PMID- 16428863
TI  - Ca2+ clearance in smooth muscle: lessons from gene-altered mice.
AB  - The regulation of intracellular [Ca(2+)](i) is important for all cells, but in
      particular for smooth muscle, as [Ca(2+)](i) is a key second messenger leading to
      contraction. Mechanisms for the cellular clearance of [Ca(2+)](i) form one side
      of Ca(2+) homeostasis and include: Plasma Membrane Ca(2+) ATPases (PMCA),
      Sarcoplasmic/Endoplasmic Reticulum Ca(2+) ATPases (SERCA), Na(+)-Ca(2+)
      exchangers (NCX) when coupled to the Na(+)-K(+) ATPases (NKA) and in some cases
      mitochondria. The nature and relative contribution of these various components of
      cytosolic Ca(2+) clearance have long been an important topic for study in smooth
      muscle, particularly as related to regulation of contractility. These studies
      have largely depended on inhibition of the various components. Recently advances
      in gene-targeting and transgenesis have made it possible to add or delete
      individual components, and importantly specific isoforms from the cell. In this
      brief review, we will focus on new information on Ca(2+) clearance in smooth
      muscle gained from studies on gene-altered mice models. These provide a deeper
      understanding of distinct functional roles for individual isoforms and the
      interactions between various components.

PMID- 16428864
TI  - Effects of different alpha-1 adrenoceptor blockers on proximal urethral function
      using in vivo isovolumetric pressure changes.
AB  - The effects of different alpha-1 adrenoceptor blockers on the urethra and the
      cardiovascular system were evaluated using an in vivo isovolumetric intra
      urethral pressure model in New Zealand white rabbits. The urethra of anesthetized
      male rabbits was cannulated through the bladder and secured at the vesico
      urethral junction. The distal side of urethra under the pubic bone was also
      closed to allow measurement of the intra-urethral pressure. Both the intra
      urethral pressure and the femoral arterial pressure were monitored. The effects
      of five different alpha-1 adrenoceptor blockers on the increases in both the
      intra-urethral pressure and blood pressure induced by phenylephrine were then
      examined. The inhibition rate of the alpha-1 adrenoceptor blockers prazosin,
      bunazosin, terazosin, alfuzosin and tamsulosin on the increase in intra-urethral
      pressure caused as a result of contraction by phenylephrine was 87.5 +/- 4.5%
      (mean +/- S.E.), 88.0 +/- 7.2%, 86.2 +/- 6.2%, 81.4 +/- 4.8% and 92.5 +/- 5.0%
      respectively. The potency ranking of these alpha-1 adrenoceptor blockers was
      tamsulosin > bunazosin > prazosin > terazosin > alfuzosin. Their inhibition rate
      of the arterial pressure increase induced by phenylephrine was 81.9 +/- 5.0%,
      86.2 +/- 5.9%, 76.0 +/- 6.0%, 63.6 +/- 5.7% and 58.0 +/- 5.2% respectively, with
      a potency ranking of bunazosin > prazosin > terazosin > alfuzosin > tamsulosin.
      We therefore conclude that the alpha-1 adrenoceptor blockers bunazosin and
      prazosin have a more potent action on both the urethra and the vascular system.
      However, tamsulosin and alfuzosin displayed a marked blockade of the increased
      urethral pressure induced by phenylephrine, with much less of a blockade of
      arterial pressure. In the present study, tamsulosin has been shown to be the most
      sensitive and powerful of the alpha-1 adrenoceptor blockers on urethral smooth
      muscle.

PMID- 16428865
TI  - Epithelium-dependent and -independent inhibitory effects of sivelestat, a
      neutrophil elastase inhibitor, on substance P-induced contraction of airway
      smooth muscle in lipopolysaccharide-treated guinea-pigs.
AB  - The underlying mechanism involved in the interaction between neutrophil elastase
      inhibitors and tachykinins has not been elucidated. In this study we have
      examined the effects of sivelestat, a neutrophil elastase inhibitor, on the in
      vitro responses of airways from lipopolysaccharide (LPS)-untreated or -treated
      guinea-pigs to substance P. Substance P (0.01-30 micromol/l) produced
      concentration-dependent contractions of both tracheal and bronchial ring
      preparations of LPS-untreated or -treated guinea-pigs. Responsiveness to
      substance P in these isolated airway preparations was augmented by either
      epithelium removal or LPS treatment. In epithelium-intact tracheal ring
      preparations isolated from LPS-untreated guinea-pigs, sivelestat (100 micromol/l)
      significantly inhibited substance P-induced contractions. The inhibitory action
      was markedly attenuated by pretreatment with L-NAME (100 micromol/l) or
      indomethacin (2 micromol/l), and was almost undetected following removal of the
      epithelium. On the other hand, in bronchial ring preparations isolated from LPS
      untreated guinea-pigs, sivelestat had only a very slight effect on substance P
      induced contraction of the epithelium-intact preparation, whereas sivelestat
      greatly inhibited contraction in epithelium-removed bronchial ring preparations.
      In LPS-treated guinea-pigs, whether the epithelium was intact or not, sivelestat
      significantly inhibited the substance P-induced contraction of bronchial ring
      preparations. Pretreatment with L-NAME (100 micromol/l) or indomethacin (2
      micromol/l) did not affect the inhibitory effect of sivelestat in bronchial ring
      preparations. In conclusion, epithelium removal or LPS treatment induced
      hyperreactivity to substance P in the guinea-pig airway. Sivelestat caused
      epithelium-, nitric oxide- and prostaglandin-dependent inhibition of the
      substance P-induced contraction of isolated guinea-pig tracheal ring
      preparations. In contrast, the inhibitory effect of sivelestat on substance P
      induced contraction of guinea-pig bronchial ring preparations is mediated by
      epithelium-, nitric oxide- and prostaglandin-independent mechanisms. Sivelestat
      may be effective in reducing the airway hyperresponsiveness to tachykinins
      induced by epithelial injury as occurs in LPS-mediated inflammatory lung
      diseases.

PMID- 16428866
TI  - Acetylcholine-induced aortic relaxation studied in salbutamol treated rats.
AB  - It has been proposed that the acetylcholine (ACh)-induced relaxation of the rat
      aorta is entirely mediated by endothelium derived-nitric oxide (NO). However,
      some authors have reported that indomethacin pretreatment attenuates ACh-induced
      relaxation of rat aortic ring preparations. Moreover, it has also been suggested
      that cAMP accumulation may regulate either nitric oxide synthase (NOS) or
      cyclooxygenase (COX) expression in different tissues. Thus, in this in vitro
      study we have investigated the endothelial mechanisms involved in the ACh-induced
      relaxation of ring preparations of the rat thoracic aorta, as well as the
      influence chronic treatment with the selective beta(2)-agonist salbutamol had
      upon such mechanisms. Results of functional experiments show that N(G)-monomethyl
      L-arginine (L-NMMA, 3 x 10(-4) M) considerably inhibited the ACh-induced
      relaxation of rat aortic ring preparations. However, indomethacin (10(-5) M) was
      also found to partially attenuate this ACh response, suggesting that although NO
      is the most important mediator of the ACh-induced relaxation of the rat aortic
      ring preparations, vasorelaxation may also involve prostanoids. Moreover, the
      results suggest that treatment with salbutamol failed to produce any change in
      the ACh-induced relaxation of rat aortic ring preparations.

PMID- 16428867
TI  - Characterization of the genus Bifidobacterium by automated ribotyping and 16S
      rRNA gene sequences.
AB  - In order to characterize the genus Bifidobacterium, ribopatterns and
      approximately 500 bp (Escherichia coli positions 27 to 520) of 16S rRNA gene
      sequences of 28 type strains and 64 reference strains of the genus
      Bifidobacterium were determined. Ribopatterns obtained from Bifidobacterium
      strains were divided into nine clusters (clusters I-IX) with a similarity of 60%.
      Cluster V, containing 17 species, was further subdivided into 22 subclusters with
      a similarity of 90%. In the genus Bifidobacterium, four groups were shown
      according to Miyake et al.: (i) the Bifidobacterium longum infantis-longum-suis
      type group, (ii) the B. catenulatum-pseudocatenulatum group, (iii) the B.
      gallinarum-saeculare-pullorum group, and (iv) the B. coryneforme-indicum group,
      which showed higher than 97% similarity of the 16S rRNA gene sequences in each
      group. Using ribotyping analysis, unique ribopatterns were obtained from these
      species, and they could be separated by cluster analysis. Ribopatterns of six B.
      adolescentis strains were separated into different clusters, and also showed
      diversity in 16S rRNA gene sequences. B. adolescentis consisted of heterogeneous
      strains. The nine strains of B. pseudolongum subsp. pseudolongum were divided
      into five subclusters. Each type strain of B. pseudolongum subsp. pseudolongum
      and B. pseudolongum subsp. globosum and two intermediate groups, which were
      suggested by Yaeshima et al., consisted of individual clusters. B. animalis
      subsp. animalis and B. animalis subsp. lactis could not be separated by
      ribotyping using Eco RI. We conclude that ribotyping is able to provide another
      characteristic of Bifidobacterium strains in addition to 16S rRNA gene sequence
      phylogenetic analysis, and this information suggests that ribotyping analysis is
      a useful tool for the characterization of Bifidobacterium species in combination
      with other techniques for taxonomic characterization.

PMID- 16428868
TI  - Isolation and identification of methylobacterium species from the tap water in
      hospitals in Japan and their antibiotic susceptibility.
AB  - Contamination of tap water by Methylobacterium species has become a serious
      concern in hospitals. This study was planned to examine the distribution of
      Methylobacterium species inhabiting tap water used in Japanese hospitals and
      antibiotic sensitivity of the isolates in 2004. Species identification of 58
      isolates was performed based on the homology of a partial sequence of 16S rDNA.
      The dominant Methylobacterium species in hospital water were M. aquaticum and M.
      fujisawaense. To examine the biochemical properties of these isolates, a carbon
      source utilization was tested using an API50CH kit. The phenotypic character
      varied widely, and was not necessarily consistent with the results of phylogenic
      analysis based on the partial 16S rDNA sequence, suggesting that the biochemical
      properties are not suitable for identification of Methylobacterium species. The
      isolates were also subjected to antibiotic sensitivity tests. They were resistant
      to 8 antibiotics, but highly sensitive to imipenem (MIC90 = 1 microg/ml) and
      tetracycline (MIC90 = 8 microg/ml). These findings concerning the isolates
      revealed the presence of Methylobacterium species with resistance to multiple
      antibiotics in hospital tap water.

PMID- 16428869
TI  - Correlation between the anti-virus-induced cytopathic effect activity of
      interferon-alpha subtypes and induction of MxA protein in vitro.
AB  - There are several interferon-alpha (IFN-alpha) subtypes. Mechanism of disparity
      in biological effects among members of IFN-alpha subtypes remains unexplained.
      Biological activity of IFN-alpha is mediated in part by induction of
      intracellular antiviral proteins. We studied whether differences in biologic
      effects of IFN-alpha subtypes may rely on their antiviral protein inducing
      effect. Intracellular induction of MxA protein and anti-virus-induced cytopathic
      effect (CPE) activity of 11 IFN-alpha subtypes in human amnion WISH cells have
      been studied. MxA protein quantitation in cell lysates was performed by
      immunochemiluminescence assay and anti-virus-induced CPE activity was assessed by
      protection against vesicular stomatitis virus (VSV)-induced CPE. Range of MxA
      values was high when cells were treated with 10 and 100 IU/ml of each IFN-alpha
      subtype. Levels of MxA correlated with anti-VSV-induced CPE obtained with 10
      IU/ml IFN-alpha subtype. Together our data show a disparity in MxA-inducing
      activity of IFN-alpha subtypes and suggest that differences in anti-VSV-induced
      CPE of IFN-alpha subtypes in WISH cells can be related to their different ability
      to induce MxA.

PMID- 16428870
TI  - Multigenic relation to the attenuation of rabies virus.
AB  - Rabies virus Nishigahara strain causes lethal infection in adult mice after
      intracerebral inoculation. On the other hand, the RC-HL strain, derived from the
      Nishigahara strain, does not cause lethal infection in adult mice. We previously
      demonstrated that a chimeric virus, R(G), with the open reading frame of the G
      gene (G-ORF) from the Nishigahara strain in the background of the RC-HL genome,
      is virulent. Reversely, in order to demonstrate that the G gene of the RC-HL
      strain is related to the attenuated phenotype, we established a reverse genetics
      system of the Nishigahara strain and generated a chimeric virus, Ni(G), with the
      G-ORF from RC-HL in the background of the Nishigahara genome. Contrary to our
      prediction, Ni(G) killed adult mice after intracerebral inoculation with
      neuropathic symptoms like those of Nishigahara strain infection. Therefore, the G
      ORF of the RC-HL strain is not the sole determinant of the attenuated phenotype.
      In additional investigation, we examined other genes, including N, P, M and L
      genes, and generated chimeric viruses exhaustively. We found that chimeric
      viruses with a single gene from the RC-HL were not attenuated and that chimeric
      viruses with the G-ORF and at least one other ORF from the RC-HL were attenuated.
      In conclusion, attenuation from the Nishigahara to RC-HL strain is multigenic.

PMID- 16428871
TI  - Homologous recombination with linear DNA to insert antigenic protein in the
      flagellin: improvement of the Th1 immune response.
AB  - Bacterial flagellin is a surface protein with numerous advantages for the
      presentation of exogenous peptides. However, the production of recombinant
      bacteria and the expression of fusion proteins is laborious and time consuming.
      Here, we present a simple way to produce modified bacteria. Partially deleted,
      non-functional, chromosomal flagellin gene (fliC ) was changed using homologous
      recombination by a functional linear fliC gene in which we introduced an
      exogenous oligonucleotide encoding for the peptide of interest. The modified fliC
      gene was produced by polymerase chain amplification. Linear amplicons were
      introduced into the non-motile E. coli by electroporation. The formation of
      functional flagellar filaments allowed the discrimination of motile transformants
      from non-motile, non-transformed cells. Thus antibiotic selection and gene
      expression inductors are not required since transformed bacteria can be easily
      isolated and used as a vector and adjuvant for immunization. To validate this
      hypothesis, we studied the immune response against the N-terminal peptide of
      Clostridium tyrobutyricum flagellin fragment. BALB/c mice were immunized either
      with the protein displayed as flagellin fusion protein on the surface of E. coli,
      with the recombinant protein in Freund's adjuvant (FA), or with the pcDNA3 vector
      bearing the DNA fragment encoding this protein. Immunization with the flagellin
      recombinant bacteria induced a strong Th1 response as measured by high level of
      IFN-gamma production and the lack of IL-4 production. The results indicate that
      the flagellar filament protein carrying a specific epitope can be a potent
      inducer of the Th1 cellular response.

PMID- 16428873
TI  - Organic solvent-selective domain of the resistance-nodulation-division-type
      xenobiotic-antibiotic transporters of Pseudomonas aeruginosa.
AB  - The hydrophobic substrate-selective domain of the resistance-nodulation-division
      type xenobiotic transporter of Pseudomonas aeruginosa was assigned based on the
      different organic-solvent selectivities of MexB and MexY. The MexB-MexY hybrid
      protein consisting of two large periplasmic domains of MexB and the transmembrane
      domains of MexY showed MexB-type organic solvent selectivity. The results imply
      that the resistance-nodulation-division-type xenobiotic transporters recognize
      hydrophobic substrates such as organic solvents by their periplasmic domains and
      expel them to the external milieu. This is an elegant way to protect the
      cytoplasmic membrane from membrane-deteriorating agents.

PMID- 16428872
TI  - Molecular identification of Ehrlichia species and 'Candidatus Neoehrlichia
      mikurensis' from ticks and wild rodents in Shizuoka and Nagano Prefectures,
      Japan.
AB  - A total of 293 ticks and 111 wild rodents that were collected in Shizuoka and
      Nagano Prefectures, Japan, were examined for infection of Ehrlichia species and
      'Candidatus Neoehrlichia mikurensis.' The 16S rDNA or the omp-1 gene of these
      bacterial DNAs were detected from the spleens of tick-inoculated mice (5
      positive/total 29 mice) or from the spleens of wild rodents (25 positive/total
      111 rodents) by PCR amplifi-cation. Sequencing of the 16S rDNA revealed Ehrlichia
      spp. from the 5 tick-inoculated mice and 8 wild rodents, and 'Candidatus N.
      mikurensis' from 17 wild rodents. The data suggest the presence of additional
      genetic variants, and potential vectors and/or reservoirs for these bacteria in
      central Japan.

PMID- 16428874
TI  - Genotype analysis of the variable internal repeat region in the rRNA gene of
      Trichophyton tonsurans isolated from Japanese Judo practitioners.
AB  - Tinea capitis due to Trichophyton tonsurans is currently epidemic among Japanese
      Judo practitioners. T. tonsurans has seven genotypes in a variable internal
      repeat (VIR) region of the rRNA gene. All 101 isolates obtained from Japanese
      Judo practitioners had the identical genotype. This suggests that a specific
      genotype strain occurs throughout Japan.

PMID- 16428875
TI  - Analysis of six new genes encoding lysis proteins and coat proteins in
      Escherichia coli group A RNA phages.
AB  - Group A RNA phages consist of four genes-maturation protein, coat protein, lysis
      protein and replicase genes. We analyzed six plasmids containing lysis protein
      genes and coat protein genes of Escherichia coli group A RNA phages and compared
      their amino acid sequences with the known proteins of E. coli(group A),
      Pseudomonas aeruginosa(PP7) RNA phages and Rg-lysis protein from Qbeta phage. The
      size of lysis proteins was different by the groups but the coat proteins were
      almost the same size among phages. The phylogenetic analysis shows that the sub
      groups A-I and A-II of E. coli RNA phages were clearly dispersed into two
      clusters.

PMID- 16428876
TI  - Confirmation of the anomeric structure of galacturonic acid in the galacturonosyl
      ceramide of Sphingomonas yanoikuyae.
AB  - The anomeric structure of glycosphingolipids significantly influences their
      activity to stimulate natural killer T cells. In this study the chemical
      structure of the galacturonosyl-ceramide in Sphingomonas yanoikuyae, designated
      GSL-1'sy, was re-examined to prove the anomeric structure of the Dgalacturonic
      acid (GalA) in the lipid, which was reported as beta-configuration by Naka et
      al., but was suggested as alpha-configuration in our preliminary study. GSL-1'sy
      was purified from the bacterial cells with the same procedure as Naka et al. The
      1H-NMR analysis of GSL-1'sy revealed that the coupling constant of the anomeric
      proton of GalA was 3.0 Hz, indicating that GalA in GSL-1'sy is alpha-anomer, the
      configuration active for the stimulation of natural killer T cells.

PMID- 16428877
TI  - Highly pathogenic H5N1 influenza virus causes coagulopathy in chickens.
AB  - Severe hemorrhage at multiple organs is frequently observed in chickens infected
      with highly pathogenic avian influenza (HPAI) A viruses. In this study we
      examined whether HPAI virus infection leads to coagulation disorder in chickens.
      Pathological examinations showed that the fibrin thrombi were formed in
      arterioles at the lung, associated with the viral antigens in endothelial cells
      of chickens infected intravenously with HPAI virus. Hematological analyses of
      peripheral blood collected from the chickens revealed that coagulopathy was
      initiated at early stage of infection when viral antigens were detected only in
      the endothelial cells and monocytes/macrophages. Furthermore, gene expression of
      the tissue factor, the main initiator of blood coagulation, was upregulated in
      the spleen, lung, and brain of HPAI virus-infected chickens. These results
      suggest that dysfunction of endothelial cells and monocytes/macrophages upon HPAI
      virus infection may induce hemostasis abnormalities represented by the excessive
      blood coagulation and consumptive coagulopathy in chickens.

PMID- 16428878
TI  - From isolated ultrafiltration to blood-temperature-controlled feedback: an
      odyssey started by Jonas Bergstrom.

PMID- 16428879
TI  - Dialysis, ultrafiltration, and blood pressure. 1976.

PMID- 16428881
TI  - Gene expression profiling: a 'fishing expedition' in search of dialysis
      biocompatibility.

PMID- 16428882
TI  - uPAR (CD87) as a biocompatibility marker of dialysis membrane.
AB  - BACKGROUND/AIMS: Hemodialysis (HD) therapy may lead to functional changes in
      patient leukocytes. For example, the upregulation of inflammatory cytokines, such
      as IL-1beta and TNFalpha, has been well characterized. However, these findings do
      not explain the entire response of leukocytes in HD. In this study, we carried
      out a comprehensive gene expression analysis in leukocytes treated with various
      dialysis membranes using DNA microarrays. The identified gene has the potential
      to be a new marker for testing dialysis membrane biocompatibility. METHODS: Gene
      expression profiles were compared between a group of leukocytes treated with
      various dialysis membranes and an untreated group by using DNA microarray
      analysis. Expression was confirmed by quantitative RT-PCR. The expression of the
      gene product (leukocyte surface protein) was examined in 20 chronic HD patients
      by flow cytometry. RESULTS: In addition to the inflammatory cytokines, the
      urokinase plasminogen activator receptor (uPAR or CD87) gene was induced in
      leukocytes treated with each dialysis membrane. The extent of induction depended
      on the membrane's material composition. The expression of the uPAR (CD87) protein
      on leukocytes was markedly increased in patients undergoing dialysis therapy. The
      magnitude of uPAR (CD87) protein expression was correlated with clinical
      findings, i.e., the degree of leukopenia and the expression of adhesion
      molecules. CONCLUSIONS: The gene and protein expression of uPAR (CD87) depended
      on the dialysis membrane material and correlated closely with clinical findings.
      These results suggest that uPAR has the potential to serve as a marker not only
      for clinical use but also for the development of new dialysis membranes.

PMID- 16428883
TI  - Post-operative delirium is associated with poor cognitive outcome and dementia.
AB  - The objective of the present study is to evaluate the association between the
      occurrence of delirium and the cognitive outcome in elderly subjects. Hospital
      files of 572 patients who underwent hip or knee replacement between 1998 and 2004
      were examined. A sample of 90 elderly subjects (31 with evidence of post
      operative delirium), non-demented at baseline, was screened for cognitive decline
      and dementia. Diagnosis of dementia was highly associated with the occurrence of
      delirium. The relative risk for the diagnosis of dementia among subjects with
      previous history of delirium, according to the IQcode screening, was 10.5 (95%
      CI: 3.3-33.2). Such patients had a significantly higher mean IQcode score (3.75)
      as compared to controls (3.1; p < 0.001). Cognitive functions most affected in
      these patients were memory, orientation and abstract thinking. We conclude that
      the occurrence of post-operative delirium in cognitively unimpaired elderly
      subjects is associated with a worse cognitive outcome and an increased risk of
      dementia.

PMID- 16428884
TI  - Association between glycogen synthase kinase-3beta genetic polymorphism and late
      onset Alzheimer's disease.
AB  - Aberrant phosphorylated tau is the major component of the neurofibrillary tangles
      in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3beta (GSK-3beta)
      phosphorylates tau protein, and increased GSK-3beta expression has been
      associated with neurofibrillary tangles. Saitohin (STH) is a recently identified
      protein that shares tissue expression pattern with tau, and previous evidence in
      the Spanish population indicated that a polymorphism at codon 7 (Q7R) of the STH
      gene was associated with late-onset AD. Since both GSK-3beta and STH are related
      to tau, we examined the association between a polymorphism in the promoter region
      (-50) of the GSK-3beta gene and AD, either through an independent effect or
      through interaction with the STH (Q7R) polymorphism, in a well-defined group of
      333 sporadic AD patients and 307 control subjects from Spain. The current study
      reveals that GSK-3beta (-50) TT genotype is associated with an increased risk (OR
      1.99, p = 0.003) for late-onset (after the age of 72 years) AD. Our results
      indicate that both the GSK-3beta (-50) and STH (Q7R) polymorphisms increase the
      risk of late-onset (subjects >72 years) AD, although they appear to be
      independent and thus not to interact synergistically.

PMID- 16428885
TI  - Giant left-ventricular pseudoaneurysm following silent myocardial infarction.

PMID- 16428886
TI  - Pregnancy outcome following a previous spontaneous abortion (miscarriage).
AB  - OBJECTIVE: To determine the pregnancy outcome following a previous spontaneous
      abortion (miscarriage). METHOD: A prospective cohort study was done on 300
      gravida-2 patients: 200 patients (case group) whose previous pregnancy was
      spontaneously aborted (early abortion), and 100 patients (control group) whose
      previous pregnancy went to term and a live fetus was delivered. All the patients
      were followed until delivery, and then the pregnancy outcomes, neonatal
      complications and delivery routes were determined and compared between the 2
      groups. Pregnancy outcomes included: maternal complications (e.g. placenta
      previa, placental abruption, premature rupture of the membranes, preeclampsia and
      eclampsia, abortion, breech presentation, preterm labor, intrauterine fetal
      death); neonatal complications (low birth weight, gross congenital malformations,
      low Apgar score at 1 min), and delivery routes (cesarean delivery or instrumental
      delivery, e.g. forceps or vacuum). Statistical analysis was performed using the
      Statistical Package for Social Science. RESULTS: Statistical analysis showed that
      the pregnancy complications following a previous spontaneous miscarriage were no
      different from those of the control group, except for abortion (16.5 vs. 11%, p <
      0.003, RR = 1.15, CI 95% = 0.95-1.39), fetal deaths (1.5 vs. 0%, p < 0.004, RR =
      1.51, CI 95% = 1.39-1.63), and vaginal bleeding during the first trimester (19
      vs. 1%, p < 0.001, RR = 1.57, CI 95% = 1.41-1.75), which were more than those of
      the control group. Also, the rate of cesarean delivery (28.14 vs. 13.48%) was
      increased (p = 0.026, RR = 1.25, CI 95% = 1.07-1.47). Neonatal complications were
      not statistically significantly different in comparison with the control group.
      CONCLUSION: A prior spontaneous miscarriage is a risk for the next pregnancy, and
      the risk of abortion and intrauterine fetal death will increase. Therefore,
      careful prenatal care is mandatory.

PMID- 16428887
TI  - Efficacy of interferon therapy in elderly patients with chronic hepatitis C.
AB  - OBJECTIVE: We assessed the efficacy and safety of interferon (IFN) monotherapy in
      84 elderly patients aged > or =65 years with chronic hepatitis C in a
      retrospective cohort study. METHODS: Twenty-two of the 84 elderly patients were
      treated with IFN at a dose of 6 million units daily for 6-8 weeks, 18 patients
      were treated 2-3 times a week for 24 weeks and 44 patients were treated daily for
      2-8 weeks and 2-3 times a week for 16-24 weeks. RESULTS: A sustained virological
      response (SVR) occurred in 35.7% (30/84) of the patients by intention-to-treat
      analysis. Multivariate analysis showed that patients achieved a significant SVR
      when: (1) serum HCV-RNA level before IFN therapy was <100 KIU/ml (p < 0.0001) and
      (2) staging of liver fibrosis was mild (p = 0.040). Eleven (13.1%) patients
      discontinued the IFN regimen due to adverse events. Regarding factors predicting
      discontinuation of IFN, univariate analysis showed that patients aged >70 years
      were prone to drop out of therapy due to adverse events in IFN therapy (p =
      0.009). CONCLUSION: Our results suggest that IFN administration is suitable for
      65- to 70-year-old patients with chronic hepatitis C without genotype 1b and high
      virus load.

PMID- 16428888
TI  - A new HBsAg screening assay designed for sensitive detection of HBsAg subtypes
      and variants.
AB  - The design of a new HBsAg screening assay, the Hepanostika HBsAg Ultra is based
      on the use of monoclonal antibodies raised against native wild-type HBsAg and
      reactive with HBsAg in which the common 'a'-determinant is modified by site
      directed mutagenesis of four of the cysteine moieties. The design was checked
      using the same cysteine variants and samples from patients known to be infected
      with HBsAg variants. The results found were compared with other state-of-the-art
      commercial screening assays. The design of the Hepanostika HBsAg Ultra enabled
      detection of all variant HBsAg-positive samples in contrast to the other
      commercial assays. An additional 980 samples were tested to assess the
      specificity and sensitivity of the Hepanostika HBsAg Ultra. Screening of presumed
      negative serum and plasma samples resulted in a specificity of 100%. This makes
      the Hepanostika HBsAg Ultra the first screening assay with a design able to
      detect HBsAg variants with high sensitivity and specificity.

PMID- 16428889
TI  - Ugandan Kaposi's sarcoma-associated herpesvirus phylogeny: evidence for cross
      ethnic transmission of viral subtypes.
AB  - OBJECTIVE: The aim of this study was to test the relationship between Kaposi's
      sarcoma-associated herpesvirus (KSHV) phylogeny and host ethnicity at the within
      country scale. METHODS: KSHV genomic DNA samples were isolated from 31 patients
      across eleven Ugandan ethnic groups. Amino acid sequences of the ORF-K1 gene were
      used to construct a neighbor-joining phylogenetic tree. RESULTS: A5 and B1
      variants predominated with no evidence of distinct ethnic or geographic
      distribution. A new K1 subtype (F) was identified in a member of the Bantu Gisu
      tribe and a new subtype B variant (B3) among members of the Bantu Ganda tribe.
      CONCLUSIONS: The phylogeny may yet be structured by host ethnicity if members of
      Ugandan groups have convoluted biological origins, even as they identify with
      single tribes. An alternative possibility is that KSHV subtype evolution may have
      preceded major diversification of sub-Saharan Africans into ethnicities as we
      know them today, with ethnic groups beginning their histories already hosting
      multiple subtypes. A third alternative is that horizontal transmission of
      multiple KSHV subtypes may have broken up vertical lineages of the virus passed
      down within Ugandan populations.

PMID- 16428891
TI  - Characterization of naturally occurring and Lamivudine-induced surface gene
      mutants of hepatitis B virus in patients with chronic hepatitis B in India.
AB  - BACKGROUND: Besides vaccine escape or immune escape hepatitis B virus (HBV)
      mutants, naturally occurring and drug-induced mutations have been reported in the
      surface gene (S-gene) of HBV. AIM: To investigate the frequency and profile of
      naturally occurring S-gene mutants and the influence of long-term lamivudine
      therapy in patients with chronic hepatitis B (CHB). MATERIALS AND METHODS: 57
      patients with histologically proven CHB, on lamivudine 100 mg/day for more than
      24 months, were included. Viral DNA was extracted at baseline and from on-therapy
      serum samples. The region encoding the complete major hydrophilic region (MHR)
      and flanking regions (nucleotides 425-840) of major S-gene that overlapped with
      the viral polymerase was PCR amplified and sequenced. End-of-therapy response
      (ETR) was assessed. RESULTS: Two (3.5%) patients had naturally occurring HBV
      mutants, sP127S and sS143L seen in the 'a' determinant of the S-gene. Following
      lamivudine therapy, 14 of 57 (24.5%) patients developed 16 types of S-gene
      mutations (sP120S, sA128V, sS143L, sW182St., sT189I, sV190A, sS193L, sI195M,
      sW196L, sW196St., sS207R, sI208T, sS210E, sF219S, sF220L and sC221G). Thirteen
      (81.2%) of these mutations emerged downstream to the MHR. Nine of 16 types of S
      gene mutations observed with lamivudine therapy were also associated with the
      corresponding changes in the polymerase gene. Baseline viral DNA was
      significantly higher (2,093 vs. 336 pg/ml; p < 0.05) among patients developing S
      gene mutants and the ETR in them was significantly lower [3 of 16 (18.8%) vs. 17
      of 41 (41.5%); p < 0.05]. CONCLUSIONS: Naturally occurring S-gene mutations are
      uncommon and are restricted to the 'a' determinant region. Mutations develop in
      about a quarter of the patients on lamivudine therapy, mostly downstream to the
      MHR. They may contribute to non-response to the antiviral therapy.

PMID- 16428890
TI  - Testing of CpG-optimized protein and DNA vaccines against the hepatitis B virus
      in chimpanzees for immunogenicity and protection from challenge.
AB  - Despite the existence for some time of effective prophylactic vaccines, hepatitis
      B virus (HBV) infection remains an important global concern. Improvements on
      existing vaccines could be beneficial, especially in situations where it is
      desirable or necessary to induce protective immunity more rapidly or with fewer
      doses. We have compared, in chimpanzees, a current HBV vaccine that contains
      recombinant hepatitis B surface antigen HBsAg) adsorbed to alum, with two novel
      vaccine strategies that have proven superior to the current vaccine in mice. The
      first approach was the use of oligodeoxynucleotides containing CpG motifs (CpG
      ODN) as an adjuvant to Engerix-B, a commercial HBV vaccine. The addition of CpG
      ODN to Engerix-B greatly improved the kinetics and magnitude of the humoral
      response, suggesting that CpG ODN might allow induction of protective immunity in
      humans more quickly and with fewer vaccine doses. All animals receiving either
      control or CpG-containing subunit vaccines at 0 and 4 weeks attained titers of
      HBsAg-specific antibody (anti-HBs) considered protective (> or =10 mIU/ml) and
      were indeed protected from challenge at 8 weeks with 10(3.5) 50% chimp infectious
      doses (CID(50)) of intravenous HBV. The second approach was a DNA vaccine with a
      plasmid vector optimized for content of immunostimulatory CpG motifs. Despite the
      fact that earlier studies had shown four doses of a similar DNA vaccine (except
      not optimized for CpG content) to induce strong humoral responses in 1 of 2
      chimpanzees, in this study two doses of DNA vaccine (at 0 and 4 weeks) did not
      generate any detectable anti-HBs in either of 2 chimpanzees, although it did
      protect 1 that rapidly developed anti-HBs during the incubation period,
      suggesting priming of an antibody response. The poor results may be due to an
      inadequate number of doses or amount of plasmid DNA in these larger animals, but
      nevertheless point to the need to improve delivery methods for DNA vaccines for
      use in larger animals such as primates.

PMID- 16428892
TI  - Growth and production of the dengue virus in C6/36 cells and identification of a
      laminin-binding protein as a candidate serotype 3 and 4 receptor protein.
AB  - OBJECTIVES: Although dengue is one of the most common mosquito-borne viral
      diseases, few studies have investigated the relationship between the dengue virus
      and mosquito cells, and this study sought to describe the binding and propagation
      of the dengue viruses in C6/36 cells. METHODS: The internalization and production
      of the dengue virus was assayed by standard plaque assay methodologies, while
      dengue virus receptor proteins were examined by a virus overlay protein-binding
      assay and candidate gene analysis coupled with virus inhibition studies. RESULTS:
      All four serotypes were internalized linearly, and de novo virus production
      occurred 14-19 h postinfection. Virus overlay protein-binding assay identified a
      band of 50 kDa for dengue serotypes 2, 3 and 4 which comigrated with a protein
      that reacts with antibodies directed against the human 37/67-kDa high-affinity
      laminin receptor. Both antibodies directed against the human 37/67-kDa high
      affinity laminin receptor protein and soluble laminin inhibited the binding and
      internalization of serotypes 3 and 4, but not serotypes 1 and 2. CONCLUSIONS: The
      results suggest that multiple receptors may be used by the dengue virus to enter
      into insect cells, and that one of these proteins may be a laminin-binding
      protein.

PMID- 16428894
TI  - High-flow-induced arterial remodeling in rats with different susceptibilities to
      cerebral aneurysms.
AB  - BACKGROUND: The higher incidence of cerebral aneurysms (CAs) induced by enhanced
      arterial blood flow in Long Evans (LE) compared to Brown Norway (BN) rats
      suggests that intrinsic differences in high-flow arterial remodeling may be
      involved in determining CA susceptibility. Some aspects of this remodeling were
      compared in LE and BN rats after creation of an abdominal aortocaval fistula
      (ACF). METHODS AND RESULTS: At 4 days with ACF, aortic luminal cross-sectional
      area (LCSA) determined by morphometry was increased by 20% in LE but not in BN
      rats. mRNA levels, determined by RT-PCR, were higher in LE than in BN rats for
      collagen alpha1(I), collagen alpha1(III), MMP2 and its inhibitor TIMP1 at 19 days
      with ACF. Nitric oxide synthase (NOS) mRNA levels were higher in LE rats at 4
      days for the inducible (NOS2) isoform and at 4 and 19 days for the neuronal
      (NOS1) isoform. Aortic LCSA and NOS1 mRNA levels were tightly correlated and NOS
      inhibition prevented ACF-induced aortic remodeling in the LE rat. MMP2 and MMP7
      activity, evaluated by zymography at 4 days with ACF, did not greatly differ
      between BN and LE. CONCLUSIONS: These data suggest that a higher intrinsic
      ability for high-flow-induced arterial enlargement associated with NOS gene
      overexpression may be a possible genetic determinant in CA susceptibility.

PMID- 16428893
TI  - Serological assays for the detection of human andes hantavirus infections based
      on its yeast-expressed nucleocapsid protein.
AB  - BACKGROUND: The objective of the study was to develop and evaluate IgM and IgG
      ELISAs and an IgG Western blot test for the serological detection of human
      infections with Andes virus (ANDV), the major cause of hantavirus cardiopulmonary
      syndrome (HCPS) in South America. METHODS: The entire nucleocapsid (N) protein
      encoding sequence of ANDV (strain AH-1) was cloned and expressed in the yeast
      Saccharomyces cerevisiae. The polyhistidine-tagged recombinant N (rN) protein of
      ANDV was purified by nickel-chelation chromatography and characterized by its
      reactivity with different N-specific monoclonal antibodies. To detect an antibody
      response directed against ANDV in humans, indirect IgM and IgG ELISAs and an IgG
      Western blot test based on ANDV rN antigen were developed. The evaluation of the
      tests was performed using a negative serum panel and 63 blinded sera from
      Argentina and Chile, containing acute-phase and convalescent sera from HCPS
      patients. RESULTS: The specificities and sensitivities for the IgM and IgG ELISAs
      were demonstrated to be very high. The IgG ELISA data were confirmed by the IgG
      Western blot assay based on the same rN antigen. Almost all anti-ANDV-positive
      sera reacted to higher endpoint titers with N protein of ANDV than with those of
      Sin Nombre, Laguna Negra or Puumala virus. The cross-reactivity of anti-ANDV-N
      IgG-positive sera to rN proteins of other hantaviruses was found to be increased
      with time after the onset of HCPS. CONCLUSION: The high sensitivity of the novel
      assays should facilitate early diagnosis of ANDV infections and might contribute
      to a successful treatment of HCPS patients.

PMID- 16428895
TI  - An overview of hereditary hearing loss.
AB  - Understanding the genetic basis of hearing loss is important because almost 50%
      of profound hearing loss are caused by genetic factors and more than 120
      independent genes have been identified. In this review, after a brief explanation
      of some genetic terms (allele, heterozygosis, homozygosis, polymorphism, genotype
      and phenotype), classification of genetic hearing loss (syndromic versus
      nonsyndromic, and recessive dominant, X-linked and mitochondrial) was performed.
      Some of the most common syndromes (Usher, Pendred, Jervell and Lange-Nielsen,
      Waardenburg, branchio-oto-renal, Stickler, Treacher Collins and Alport syndromes,
      biotinidase deficiency and Norrie disease) causing genetic hearing loss were also
      explained briefly. The genes involved in hearing loss and genetic heterogeneity
      were presented.

PMID- 16428896
TI  - Threshold estimation in children using auditory steady-state responses to
      multiple simultaneous stimuli.
AB  - OBJECTIVE: It was the aim of this study to explore the use of auditory steady
      state response (ASSR) to multiple simultaneous stimuli for threshold estimation
      in young children. METHOD: The subjects consisted of 40 children, aged from 6
      months to 5 years, with variant degrees of sensorineural hearing loss.
      Simultaneous tonepips (0.5, 1, 2 and 4 kHz) with an amplitude modulated at
      different rates from 77 to 103 Hz were presented to both ears by insert phones.
      All children were tested with ASSR and age-appropriate behavioral tests. RESULTS:
      We found that (1) ASSR thresholds were usually higher than behavioral thresholds
      with a difference of 8-15 dB, (2) the behavioral thresholds were significantly
      correlated with ASSR thresholds (p = 0.000), and (3) there was a great difference
      between ASSR thresholds and behavioral thresholds found in a child with auditory
      neuropathy. CONCLUSION: Being objective, frequency specific and well correlated
      with behavioral thresholds, ASSR to multiple simultaneous stimuli was proven to
      be a good tool to predict behavioral hearing thresholds.

PMID- 16428897
TI  - Endoscopic resection of sinonasal hemangiomas and hemangiopericytomas.
AB  - INTRODUCTION: Endoscopic resection of benign neoplasms, such as inverted
      papilloma, has been well described. There are limited case reports of endoscopic
      resection of benign vascular tumors, including hemangiomas, or those with low
      grade malignant potential, such as hemangiopericytomas. METHODS: Retrospective
      review of sinonasal hemangiomas and hemangiopericytomas resected endoscopically
      at a single tertiary-care facility. RESULTS: Three hemangiomas and 3
      hemangiopericytomas were resected endoscopically with no recurrences at a mean
      follow-up of 22 months. Four tumors involved the skull base; 2 of these underwent
      preoperative embolization. One patient had a CSF leak that occurred as the tumor
      was removed from the cribriform plate and that was successfully repaired
      intraoperatively. The average size of the tumors was 5.8 cm x 2.7 cm with all
      tumors at least 2.5 cm in greatest dimension by computed tomography or magnetic
      resonance imaging. The largest tumor was 12 cm in greatest dimension. An average
      of 8 intraoperative frozen section margins was taken around 5 tumors, with all
      margins of each tumor clear on final pathology. Patients included 4 males and 2
      females with an average age of 47 years. CONCLUSION: Large vascular neoplasms of
      the sinonasal cavity, such as hemangiomas and hemangiopericytomas, can be safely
      removed using endoscopic techniques. Although these patients have a limited
      follow-up, it is prudent to perform long-term endoscopic follow-up in order to
      detect recurrences regardless of resection technique.

PMID- 16428898
TI  - Topical application of mitomycin C before versus after myringotomy: an
      experimental study.
AB  - The objective of this animal study was to compare topical mitomycin C (MMC)
      before and after nonlaser myringotomy. Bilateral myringotomies were performed in
      12 rats. On the left side, MMC was applied to the intact tympanic membrane for 10
      min before myringotomy (preapplication group). On the right side, MMC was applied
      to the tympanic membrane following myringotomy. Tympanic membranes were observed
      for a total of 8 weeks. By day 35, all myringotomies with application of MMC
      after perforation of the tympanic membrane were closed, whereas 42% of the
      myringotomies with application of MMC prior to perforation remained patent. One
      tympanic membrane in the preapplication group showed an enlargement of the
      perforation with partial destruction of the malleus. The present study showed
      that the application of MMC to the intact tympanic membrane prolongs the patency
      of nonlaser myringotomies in rats. Specific side effects of the MMC application
      must be kept in mind.

PMID- 16428899
TI  - Statins decrease serotonin-induced contractions in coronary arteries of swine in
      vitro.
AB  - Recent evidence suggests that statins improve the status of patients with
      coronary artery disease not only by reducing cholesterol levels, but also by
      acting at the level of the endothelium-smooth muscle unit. Previous results from
      our laboratory showed that these drugs interact with the vascular wall by
      partially inhibiting calcium-dependent, agonist-induced contractions in rat
      aortas. To evaluate whether this effect is also extended to the coronary
      vasculature, we assessed the effect of statins on serotonin (5-HT) induced
      contractions of left and right coronary arteries of swine. Concentration-response
      curves for the 5-HT-induced contractions (from 0.1 nmol/l to 100 micromol/l) were
      calculated on rings from both coronaries in the presence and absence of either (5
      micromol/l) pravastatin, mevastatin, simvastatin, lovastatin, or atorvastatin.
      After a 45-min incubation period, all statins significantly reduced the Emax for
      the 5-HT-induced contractions, ranging from 51.9 +/- 1.9% (simvastatin) to 15.9
      +/- 2.0% (pravastatin) in the left coronary artery and from 48.8 +/- 2.0%
      (simvastatin) to 17.8 +/- 2.5% (pravastatin) in the right coronary artery. The
      EC50 values for the 5-HT-induced contractions were 0.150 +/- 0.005 micromol/l for
      the left coronary artery and 0.171 +/- 0.010 micromol/l for the right coronary
      artery. These values significantly changed after incubation with statins, ranging
      from 1.240 +/- 0.101 micromol/l (for simvastatin) to 0.081+/- 0.008 micromol/l
      (for pravastatin) in the left coronary artery and from 1.410 +/- 0.075 micromol/l
      (for simvastatin) to 0.084 +/- 0.008 micromol/l (for pravastatin) in the right
      coronary artery. This evidence supports the possibility that, beyond their lipid
      lowering properties, statins may provide a beneficial effect in atherosclerotic
      patients by reducing the tone in the coronary vasculature, facilitating blood
      flow to the myocardium.

PMID- 16428900
TI  - Expiratory flow maneuvers in patients with neuromuscular diseases.
AB  - OBJECTIVES: To compare cough peak flows (CPF), peak expiratory flows (PEF), and
      potentially confounding flows obtained by lip and tongue propulsion (dart flows,
      DF) for normal subjects and for patients with neuromuscular disease/restrictive
      pulmonary syndrome and to correlate them with vital capacity and maximum
      insufflation capacity. DESIGN: A cross-sectional analytic study of 125 stable
      patients and 52 normal subjects in which CPF, PEF, and DF were measured by peak
      flow meter and vital capacity and maximum insufflation capacity by spirometer.
      RESULTS: In normal subjects and in patients, the DF significantly exceeded PEF
      and CPF (P < or = 0.001). For normal subjects, PEF and CPF were not significantly
      different. For patients with neuromuscular disease/restrictive pulmonary
      syndrome, the CPF significantly exceeded PEF (P < 0.05). No normal subjects but
      14 patients had DF lower than CPF. Thirteen of these 14 had the ability to air
      stack (maximum insufflation capacity greater than vital capacity), indicating
      greater compromise of mouth and lip than of glottic muscles. For 14 of 88
      patients, maximum insufflation capacity values did not exceed vital capacity,
      mostly because of inability to close the glottis (inability to air stack).
      Nonetheless, for 11 of these 14 patients, the DF were within a standard deviation
      of the whole patient group; thus, bulbar-innervated muscle dysfunction was not
      uniform. CPF and PEF correlated with vital capacity (r = 0.85 and 0.86,
      respectively), and with maximum insufflation capacity (r = 0.76 and 0.72,
      respectively). CONCLUSIONS: Measurements of CPF, PEF, and DF are useful for
      assessing bulbar-innervated, inspiratory, and expiratory muscle function. Care
      must be taken to not confuse them.

PMID- 16428901
TI  - Hemiplegic limb synergies in stroke patients.
AB  - OBJECTIVE: To describe the extent to which the voluntary movements of hemiparetic
      stroke patients are restricted to the hemiplegic limb synergies (which are marked
      by the inability to master individual joint movements) described by Brunnstrom.
      The study also aimed to describe the extent to which the synergies are related to
      functioning. DESIGN: In a prospective observational study design, 64 consecutive
      hemiparetic stroke patients were assessed with Brunnstrom's hemiplegic limb
      synergies, the modified Ashworth scale for spasticity, the Rivermead mobility
      index, and the Barthel ADL index. RESULTS: Three months after stroke, 8 of the 64
      patients were moving completely or partly within the synergies. All patients
      whose movements were restricted to the synergies also exhibited spasticity.
      Hemiparetic patients whose movements were restricted to the synergies had
      significantly worse functioning scores than hemiparetic patients whose movements
      were not restricted to the synergies although severe disabilities were seen in
      both groups. CONCLUSIONS: Three months after stroke, the voluntary movements of
      only 13% of hemiparetic stroke patients were restricted to the synergies. The
      synergies were associated with spasticity and activity limitations. The use of
      the synergies might only be suitable for a small fraction of hemiparetic patients
      namely, those displaying spasticity.

PMID- 16428902
TI  - Long-term exercise adherence in the elderly with chronic low back pain.
AB  - OBJECTIVE: Chronic back pain is common in the elderly population and can be
      treated with exercise. Long-term adherence to exercise recommendations has been
      documented in adults of <65 yrs of age but not for elderly adults. This study
      explored exercise behaviors of elderly adults with a history of chronic back pain
      before and 2 yrs after treatment in an exercise-oriented rehabilitation program.
      DESIGN: This study utilized a case series design to survey 126 subjects >65 yrs
      old who underwent physical therapy during the year 2000 for complaints of chronic
      low back pain. Of these, 89 (70%) responded to the 2-yr questionnaire. Outcome
      measures included visual analog scale for pain, Oswestry disability
      questionnaires, back flexibility and strength, and a questionnaire exploring
      exercise behaviors. All subjects underwent a 6-wk physical therapy program that
      consisted of exercise coupled with advice to remain active. RESULTS: Improvements
      in flexibility and strength occurred during treatment. Mean Oswestry disability
      scores (0-100 scale) improved from 32 to 20, and pain scores (0-10 scale) from
      5.0 to 3.0 during treatment (P < 0.001) and were maintained at the 2-yr follow
      up, regardless of exercise adherence. The percentage of patients who performed at
      least some exercise increased from 49% before treatment to 72% at the 2-yr follow
      up. The changes in disability or pain observed during treatment did not influence
      exercise compliance. The most frequently stated reasons for nonadherence was that
      exercise did not help or aggravated pain (33%). For those who exercised
      regularly, 80% did so because of the health benefits from exercise. CONCLUSIONS:
      The exercise behaviors of many elderly adults with chronic low back pain can
      increase after an exercise-oriented spine physical therapy program.

PMID- 16428903
TI  - Knee isometric torque and electromyographic specificities after semitendinosus
      and gracilis hamstrings anterior cruciate ligament reconstruction.
AB  - OBJECTIVES: Because the co-contraction of the gastrocnemius and hamstring muscles
      strains the anterior cruciate ligament, the role of the gastrocnemius muscle is
      of particular importance after semitendinosus and gracilis tendon autografts for
      anterior cruciate ligament reconstruction. This study aimed to examine the
      neuromuscular mechanisms underlying postsurgical torque deficits during knee
      flexion by using surface electromyography. DESIGN: A total of 14 volunteer
      patients (eight men, six women; age, 32.5 +/- 9.3 yrs; height, 172.7 +/- 6 cm;
      weight, 69.6 +/- 10.2 kg) were enrolled in the study; all had undergone anterior
      cruciate ligament reconstruction performed by the same surgeon. The neuromuscular
      mechanisms were assessed using isometric tests and surface electromyographic
      recordings at 19 mos post-reconstruction. The torque deficits in the injured knee
      were compared with the uninjured knee, which served as control values. RESULTS:
      Significant differences in torque production were observed between the two limbs
      at specific angular positions during the extension and flexion tests (P < 0.05).
      The difference in the root mean square myoelectrical activity between the limbs
      was computed at each tested position, revealing that the gastrocnemius muscle had
      greater activity at 75 degrees than at 45 degrees (P < 0.05). CONCLUSIONS: In
      deep flexion (>70 degrees), the gastrocnemius muscle may compensate for the
      weakened hamstrings and thereby strain the anterior cruciate ligament graft after
      anterior cruciate ligament semitendinosus and gracilis tendon reconstruction.

PMID- 16428904
TI  - F wave studies of neurogenic intermittent claudication in lumbar spinal stenosis.
AB  - OBJECTIVE: Lumbar spinal stenosis (LSS) may result in neurogenic claudication
      (NC), which is thought to be a result of transient ischemia during exercise. In
      this study we evaluated the changes in F wave studies before and immediately
      after walking stress in patients with NC. DESIGN: Twenty-six patients with LSS
      who had signs and symptoms of NC and 20 healthy volunteers were included in this
      study. Routine motor and sensory nerve conduction studies and tibial F wave
      studies were performed in both groups. Immediately after walking stress test,
      tibial F wave studies were repeated. Exercise treadmill protocol was used for
      ambulation. Time to first symptoms and total ambulation time were recorded.
      RESULTS: After completion of the baseline electrophysiological examination, a
      walking stress test was performed using a treadmill, and 16 patients (61.5%)
      experienced neurogenic claudication during the trial. The mean time to first
      symptoms was 2.0 +/- 3.5 mins (minimum = 0, maximum = 14). In the control group
      18 subjects (90%) completed the trial without any symptoms, and 2 (10%) subjects
      had to stop at an average of 10 mins because of generalized fatigue. Within 5
      mins after the walking stress test, tibial F wave studies were repeated in both
      groups. There were significant increases in F latency values bilaterally in the
      patient group (P = 0.001 for both sides) but not in control subjects (P = 0.435
      for right side and P = 0.122 for left side). CONCLUSION: Our data suggest that F
      wave studies after walking stress test provide more information for the diagnosis
      of NC.

PMID- 16428905
TI  - Reliability and validity of the GMFM-66 in 0- to 3-year-old children with
      cerebral palsy.
AB  - OBJECTIVE: To examine the reliability and validity of a 66-item version of the
      Gross Motor Function Measure (GMFM-66) to assess the gross motor functions of
      children <3 yrs old with cerebral palsy. DESIGN: 298 valid samples were obtained
      from 171 children with cerebral palsy (male 126, female 45, mean age 19 mos, age
      range 3-36 mos) measured with GMFM-88. Then a 73-item version of GMFM (GMFM-73)
      special for these children was obtained by Rasch analysis. GMFM-66 score and GMFM
      73 scores of each sample were obtained. The reliability and validity of GMFM-66
      were evaluated by analyzing the correlation between the scores and between the
      change scores of these two GMFM versions. The relative precision of GMFM-73 vs.
      GMFM-66 was also analyzed. RESULTS: The test-retest reliability and interscorer
      reliability of GMFM-66 were both high. The ICC scores were 0.9666 and 0.9782,
      respectively. Significant correlations were found between the scores (r = 0.9848,
      P < 0.001) and between the change scores (r = 0.8700, P < 0.001) of these two
      versions of GMFM. A 14% less gain in relative precision was achieved when using
      GMFM-73 vs. GMFM-66. CONCLUSION: Results indicated that the GMFM-66 had good
      reliability and validity in assessing the gross motor functions of children <3
      yrs old with cerebral palsy. The GMFM-73 derived in the present study did not
      function significantly better for young children than GMFM-66.

PMID- 16428908
TI  - Thromboprophylaxis in medical and surgical patients undergoing physical medicine
      and rehabilitation: consensus recommendations.
AB  - Venous thromboembolism (deep venous thrombosis with or without its major
      complication, pulmonary embolism) commonly occurs in patients undergoing
      rehabilitative therapy for various surgical or traumatic conditions and in
      patients with incapacitating medical illnesses. Thromboprophylaxis utilizes
      medications that interfere with the coagulation process and mechanical measures
      such as graded elastic stockings and intermittent pneumatic compression. To
      obtain a range of expert opinion on the optimal use of the numerous
      antithrombotic modalities now available, a consortium comprising clinical
      directors at a number of rehabilitative centers in south Florida met to review
      the literature on thromboprophylaxis in rehabilitation patients and to discuss
      the strategies followed at their respective facilities. The consortium then
      assembled a set of recommendations based on available evidence-based literature
      and established consensus on acceptable forms of thromboprophylaxis in each
      clinical condition in rehabilitation associated with an increased risk of venous
      thromboembolism.

PMID- 16428906
TI  - Effects of age and timing of augmented feedback on learning muscle relaxation
      while performing a gross motor task.
AB  - OBJECTIVE: To examine the combined effect of age and timing of augmented feedback
      on learning muscle relaxation. Performing a gross motor task, subjects had to
      lower their trapezius muscle activity using the electromyographic signal as
      visual myofeedback. DESIGN: Healthy subjects (16 young adults: 20-35 yrs; and 16
      older adults: 55-70 yrs) were randomly assigned to one of two timing conditions
      of myofeedback: concurrent (feedback was provided immediately during the trial)
      and terminal (feedback was provided delayed after the trial) condition. RESULTS:
      The results indicated that young adults had a higher level of motor performance
      (i.e., lower muscle activity) compared with older adults when myofeedback was
      provided. These effects persisted during short- (after 10 mins) and long-term
      retention (after 1 wk) when no myofeedback was provided. In contrast to young
      adults, older adults did not improve their performance throughout the experiment.
      There were no interactions of age with the timing conditions of myofeedback
      during acquisition and retention. CONCLUSIONS: Either timing condition of
      augmented feedback was equally helpful to young adults, whereas neither was
      helpful for older adults in learning muscle relaxation.

PMID- 16428910
TI  - Neuromuscular adaptations to electrostimulation resistance training.
AB  - A combination of in vivo and in vitro analyses was performed to investigate
      muscular and neural adaptations of the weaker (nondominant) quadriceps femoris
      muscle of one healthy individual to short-term electrostimulation resistance
      training. The increase in maximal voluntary strength (+12%) was accompanied by
      neural (cross-education effect and increased muscle activation) and muscle
      adaptations (impairment of whole-muscle contractile properties). Significant
      changes in myosin heavy chain (MHC) isoforms relative content (+22% for MHC-2A
      and -28% for MHC-2X), single-fiber cross-sectional area (+27% for type 1 and +6%
      for type 2A muscle fibers), and specific tension of type 1 (+67%) but not type 2A
      fibers were also observed after training. Plastic changes in neural control
      confirm the possible involvement of both spinal and supraspinal structures to
      electrically evoked contractions. Changes at the single muscle fiber level
      induced by electrostimulation resistance training were significant and
      preferentially affected slow, type 1 fibers.

PMID- 16428911
TI  - Rehabilitation after intramedullary skeletal kinetic distractor implantation: a
      report of two cases and a suggested therapy program.
AB  - Adult limb lengthening occurs via distraction osteogenesis and traditionally
      involves use of an external fixator. Complications after placement of hardware
      often disrupt rehabilitative efforts and hinder patients' progress. A completely
      internal limb-lengthening device has been developed and increasingly used, and it
      may more commonly be seen by a physiatrist in consultation for postoperative
      rehabilitation. We present two cases of patients who underwent implantation of
      the intramedullary skeletal kinetic distractor and required acute inpatient
      rehabilitation. One patient had previously suffered a malunion deformity with a
      resultant limb shortening, and the second patient was born with a congenital leg
      length inequality. Both patients had successful femoral intramedullary skeletal
      kinetic distractor implantation and were transferred for acute inpatient
      rehabilitation. Distraction occurred daily, based on the patient's level of
      physical activity in therapy, and was measured using a hand-held monitor. Both
      patients were successfully discharged home, without complications throughout the
      hospital stay. Knowledge of the theory and mechanism of action of the device is
      important to guide both the amount and type of therapy prescribed and to follow
      patient progress. We present general guidelines during the acute rehabilitation
      of a patient after intramedullary skeletal kinetic distractor surgery.

PMID- 16428912
TI  - Self-reported experience with safe transport of children with special healthcare
      needs: a rehabilitation therapist perspective.
AB  - Minimal information is available to occupational and physical therapists
      (rehabilitation therapists) regarding the safe transportation of children who
      have special healthcare needs (CSHCN). CSHCN may have conditions that impact
      their ability to be properly restrained in motor vehicles. We conducted an online
      survey of rehabilitation therapists to determine knowledge, formal training,
      experience and the amount of counseling provided to families regarding the safe
      transport of CSHCN before beginning an online training course. Eighteen percent
      (1075 of 6000) of invited rehabilitation therapists agreed to participate in the
      online survey. Most of the registered participants were physical therapists (70%)
      or occupational therapists (18%). A majority reported having little or no
      knowledge (53%), formal training (79%), or experience (54%), and conducted little
      or no counseling (61%) with families on the subject. The results of this survey
      indicate that rehabilitation therapists rate themselves as having low levels of
      knowledge, training, experience, and counseling of families regarding the subject
      of safe transportation of CSHCN. We recommend the development and implementation
      of a continuing educational program for rehabilitation therapists regarding the
      safe transportation of CSHCN.

PMID- 16428913
TI  - Dyspnea: an unusual presentation of posttraumatic syringomyelia.

PMID- 16428915
TI  - Suppression of hyperglycemia-induced superoxide formation and endothelin-1 gene
      expression by carvedilol.
AB  - Carvedilol (CV) is a beta-blocker with favorable effects on cardiovascular
      disease. To determine whether CV can prevent increases in superoxide (SO)
      production due to hyperglycemia, human umbilical vein endothelial cells (HUVEC)
      were treated with either 100 or 500 mg/dL dextrose in the presence or absence of
      0.1, 1.0, and 10 micromol/L CV. Superoxide levels were measured using the
      hydroethidine (HE) fluorescence method. Generation of SO was linear from time 0
      to 60 minutes. At 60 minutes, the HE fluorescence in cells treated with 500 mg/dL
      dextrose (123.3+/-4.9 units) was significantly higher than that in control cells
      treated with 100 mg/dL dextrose (84.0+/-3.5 units) (P<0.002). Addition of 0.1,
      1.0, and 10 micromol/L CV to cells treated with 500 mg/dL dextrose decreased SO
      generated to 113.3+/-1.8, 98.7+/-8.3, and 70.0+/-1.0 units, respectively (P<0.13,
      P<0.05, and P<0.004, respectively). Cellular endothelin-1 mRNA and endothelin-1
      protein secreted in culture media were significantly increased in the presence of
      500 mg/dL dextrose. The addition of 10 micromol/L CV significantly decreased both
      endothelin-1 (1-21) mRNA and protein levels. Measurements of media lactate
      dehydrogenase activity indicated that CV inhibited cytotoxicity caused by 500
      mg/dL dextrose. These findings suggest that CV not only prevents dextrose-induced
      SO generation in endothelial cells but may also have favorable effects on gene
      expression and cell survival.

PMID- 16428916
TI  - Cellular response of human cardiac fibroblasts to mechanically simulated aortic
      regurgitation.
AB  - Myocardial fibrosis has been identified in biopsy specimens from catheterization
      and valve replacement surgery in patients with severe chronic aortic
      regurgitation (AR). While characterization of these extracellular matrix (ECM)
      alterations has been incomplete in humans, fibrosis also has been identified in
      chronic severe experimentally created AR, in which ECM composition features
      abnormal fibronectin/glycoprotein production, with normal collagen content.
      Virtually identical ECM variations have been induced when normal rabbit cardiac
      fibroblasts (CF) are subjected in culture to cyclic mechanical strain mimicking
      that found in the left ventricle (LV) in severe AR. To determine whether the
      changes seen experimentally can be extrapolated to humans, we exposed normal
      human CF in culture to the mechanical strain employed in the experimental model
      to simulate severe AR (n=3 replications from 1 patient). CF were isolated from
      epicardial biopsy distant from diseased coronary arteries in a 38-year-old man
      with normal LV function and without prior myocardial infarction who was
      undergoing elective coronary artery bypass grafting. Gelatin Sepharose affinity
      chromatography (GSAC) and Western analysis were used to compare fibronectin
      expression in strained versus nonstrained normal human CF in tissue culture;
      Western analysis was used to compare type I collagen production. In AR-strained
      CF, fibronectin synthesis nominally increased [av 38% (Western) and 45% (GSAC)]
      relative to control; type I collagen synthesis was virtually unchanged. These
      results simulate those found experimentally and suggest that human CF, like
      rabbit CF, manifest abnormal compositional distribution of ECM proteins in AR.

PMID- 16428917
TI  - Influence of ephedrine and the role of alpha subtype adrenoreceptors in the
      vascular bed of the cat lung.
AB  - In a university research laboratory and in separate experiments, the effects of
      phentolamine, the alpha-adrenergic antagonist; prazosin, an alpha1-adrenoceptor
      antagonist; 5-methyl-urapidil, the selective alpha1A-subtype adrenoceptor
      antagonist; chloroethylclonidine, an alpha1B- and alpha1D-subtype adrenoceptor
      antagonist; and BMY 7378, a selective alpha1D-subtype adrenoceptor antagonist
      were analyzed in an attempt to identify any significant effect on pulmonary
      arterial responses to ephedrine and other agonist agents in the pulmonary
      vascular bed of the cat. Under constant flow conditions, lobar arterial perfusion
      pressure and systemic pressure were continuously monitored, electronically
      averaged, and permanently recorded. In the isolated left lower lobe of the
      pulmonary feline vascular bed, ephedrine induced a dose-dependent vasoconstrictor
      response that was not significantly altered following administration of 5-methyl
      urapidil. The vasopressor activity as a result of ephedrine was significantly
      decreased after administration of phentolamine, prazosin, chloroethylclonidine,
      and BMY 7378. Further, when the alpha1B- and alpha1D-subtype adrenoceptor
      antagonist chloroethylclonidine was given, there was almost complete elimination
      of the ephedrine-induced vasoconstrictor response. The results of this study
      suggest that ephedrine causes a dose-dependent vasopressor response in the feline
      pulmonary vascular bed and that this activity may be mediated or modulated by
      both alpha1B- and alpha1D-subtype adrenoceptor sensitive pathways.

PMID- 16428918
TI  - Screening for nephropathy and antiangiotensin use among diabetic patients in an
      academic community medical center.
AB  - The American Diabetes Association recommends routine screening for albuminuria to
      detect early nephropathy in all patients with diabetes mellitus. If nephropathy
      is identified, treatment with an antiangiotensin agent decreases progression and
      improves renal outcomes. Concordance with guidelines for nephropathy screening
      and antiangiotensin therapy among diabetic patients in a primary care setting of
      an academic community medical center was evaluated. Medical charts of adult
      patients with diabetes mellitus from February 2000 through January 2003 were
      retrospectively reviewed. In part 1 of the study, whether patients were screened
      for nephropathy at least once was recorded. In part 2 of the study,
      antiangiotensin prescribing was assessed in all patients and in subgroups
      stratified by screening. In both parts of the study, patient characteristics and
      comorbidities were assessed using multivariate analysis to determine their impact
      on the odds that a patient was screened and that antiangiotensin therapy was
      prescribed. Among the 329 patients included, 182 patients (55.3%) were screened
      for nephropathy. Patients who were screened were younger (OR=0.83 for 10-year
      increase, 95% CI: 0.69-0.99), less likely to have congestive heart failure
      (OR=0.42, 95% CI: 0.20-0.90), and more likely to be cared for by a resident
      physician directly supervised by an attending physician (OR=3.03; 95% CI: 1.82
      5.03). A total of 215 patients (65.3%) were prescribed antiangiotensin therapy.
      Hypertension was a predictor of antiangiotensin therapy among all patients who
      were screened (OR=10.34, 95% CI: 4.45-24.01), those who were screened and
      negative (OR=15.46, 95% CI: 5.56-42.98), and those who were not screened
      (OR=10.79, 95% CI: 4.39-26.52). Among patients screened for nephropathy, coronary
      artery disease (OR=3.01, 95% CI: 1.05-8.63), and the presence of proteinuria
      (OR=4.26, 95% CI: 1.61-11.24) were predictors of antiangiotensin use. This study
      found that the likelihood of screening for nephropathy among diabetic patients
      was inversely associated with a diagnosis of congestive heart failure and
      increasing age. Conversely, care by a resident physician directly supervised by
      an attending physician increased the odds that patients would be screened. A
      diagnosis of hypertension and the presence of albuminuria were each associated
      with increased use of an antiangiotensin agent.

PMID- 16428919
TI  - Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo.
AB  - Ginkgo biloba extract is one of the most widely used herbal products in the
      United States. However, bleeding episodes in patients taking Ginkgo biloba and
      warfarin have been documented. Therefore, in vitro and in vivo inhibition studies
      were done to ascertain the influence of ginkgo on CYP2C9, the P-450 isozyme
      responsible for the metabolism of the most potent warfarin enantiomer, (S)
      warfarin. Ginkgo extract inhibited human liver microsomal CYP2C9 with an apparent
      Ki=14.8 microg/mL, and the inhibition was increased by acid hydrolysis (apparent
      Ki=9.1 microg/mL). Two open-label, crossover pharmacokinetic studies in healthy
      subjects were performed using tolbutamide and diclofenac as probe CYP2C9
      substrates. In contrast to the in vitro inhibition of CYP2C9, no interactions
      between Ginkgo biloba extract and CYP2C9 probe substrates were observed in vivo
      as evidenced by the lack of effect on the steady-state pharmacokinetics of
      diclofenac or on the urinary metabolic ratio of tolbutamide.

PMID- 16428920
TI  - Development of a dry powder inhaler, the Ultrahaler, containing triamcinolone
      acetonide using in vitro-in vivo relationships.
AB  - Triamcinolone acetonide (TAA) is safe and effective corticosteroid that is
      marketed as an MDI (metered dose inhaler) (Azmacort) for the treatment of asthma.
      A novel dry powder inhaler (DPI), the Ultrahaler, has been developed to deliver
      Azmacort as another alternative to provide non-CFC formulation for the asthmatic
      patients. The Ultrahaler is breath actuated and, unlike MDI, does not require
      coordination of inhalation with the actuation of the device. However, with the
      Ultrahaler device, like any dry powder inhalation device, the challenge was the
      on-target and uniform delivery of the drug at the site of action (lungs) with
      different dose strengths. Due to the complexities of oral inhaled formulations
      and the topical nature of drug delivery to the lung for efficacy, the
      reformulation requires careful consideration and support throughout their
      development, using a combination of in vitro and in vivo studies. This paper
      describes in vitro studies and two clinical pharmacokinetic studies conducted in
      a sequence that helped to establish optimum doses for the Ultrahaler. In vitro
      data were used to guide the initial selection of doses that were then compared in
      vivo using a pharmacokinetic study with a charcoal block. The in vitro tests
      included quantifying the target-delivered dose, dose uniformity throughout the
      life of the device, and the particle size distribution. Particle size
      distribution was measured using multistage liquid impinger (MSLI) or the Andersen
      Cascade Impactor (ACI). For in vitro testing, TAA was measured by HPLC methods.
      Based on the preliminary in vitro data for the respirable fraction, dose
      strengths with an MDI and the Ultrahaler for the first study were determined. The
      in vivo assessment consisted of a four-way crossover study following oral
      inhalation using both MDI (75 and 225 microg/actuation, reference treatment) and
      comparable respirable doses in the DPI (130 and 360 microg/actuation) devices in
      healthy volunteers in the presence (lung deposition) and absence (lung and
      oropharynx deposition) of the charcoal block. Plasma TAA concentrations were
      determined using a radioimmunoassay (RIA) method. The in vitro data also showed
      dose proportionality with DPI formulation, and the doses delivered were within
      13% of the target doses. A measure of dose uniformity, the relative standard
      deviation (%RSD) of dose, was less than 15%. Plasma TAA exposure of DPI
      formulations was compared with that of MDI formulations. Mean ratios (DPI/MDI) of
      the AUCinf were close to unity for the lower dose strength. However, for the
      higher dose strength, plasma exposure was higher with the Ultrahaler formulation
      as compared with the MDI formulation (mean AUCinf DPI/MDI ratios: 1.96). These
      differences seem to be due to less than proportional increases in the MDI
      formulation. Based on these results and using the higher dose strength of the MDI
      as the comparator, the new dose strengths of the Ultrahaler were chosen, ie, 100,
      225, and 450 mug/actuation. Plasma TAA concentrations were measured by LC/MS/MS
      methods. The mean TAA concentrations and AUCinf and Cmax values increased in a
      dose-proportional manner with an increase in dose for the DPI formulation. The
      pharmacokinetic parameters showed low variability (10%-33%). Fine particle mass
      (in vitro testing) and TAA exposure in plasma following DPI administration were
      compared. Fine particle performance in vitro related well with in vivo
      pharmacokinetic performance (R=AUCinf-0.9998, Cmax-0.9956). In conclusion, in
      vitro and in vivo data were in agreement and good control over the target-dose
      delivery and dose proportionality could be achieved in the early stages of the
      development of the Ultrahaler device and were critical in guiding and ensuring
      the success of the reformulation efforts for Azmacort.

PMID- 16428921
TI  - Electrocardiographic profile of oral piperazine citrate in healthy volunteers.
AB  - The electrocardiographic (ECG) profile of oral piperazine citrate was determined
      in healthy volunteers. Piperazine caused reduction in heart rate in all the
      subjects. The highest percentage of change was 15.7. The average pretreatment
      (73.6+/-6.59 beats/min) when compared with the heart rate 1 hour after piperazine
      was administered (64.6+/-5.21 beats/min) was statistically significant
      (P=0.0054). The QT and JT intervals had average increases of 9.7% and 11.1%,
      respectively. In contrast, piperazine did not have any effect on the QRS complex
      following its administration. However, the average PR interval 1 hour after
      ingesting oral piperazine 2 g was significantly prolonged, 0.18+/-0.0063 seconds
      compared with a pretreatment average of 0.16+/-0.0098 seconds. The difference
      between the 2 values was statistically significant (P=0.0161). No dysrhythmic
      phenomena were seen. Sinus rhythm was maintained in all the volunteers, with
      every QRS-T complex preceded by a P wave. The direction and magnitude of the mean
      electric axis of QRS complex and T wave were not altered by piperazine. It is
      concluded that oral piperazine citrate induced some changes on the ECG profile of
      healthy human volunteers, typical of many potent antiarrhythmic agents.

PMID- 16428922
TI  - The differential antibacterial and gastrointestinal effects of erythromycin and
      its chiral isolates.
AB  - The use of erythromycin has been limited by the gastrointestinal side effect
      properties, which include abdominal distress and diarrhea. To evaluate the
      possibility of reducing the toxicity of erythromycin, studies were undertaken to
      separate erythromycin into chiral isolates and then to test the activity of these
      chiral isolates on gastrointestinal contractility and bacteriostatic actions.
      Gastrointestinal contractility was obtained by the use of isolated strips of a
      rat colon. Antibacterial activity was used by obtaining the MICs of erythromycin
      and isolated agents against Enterococcus faecalis ATCC 29212. ANOVA was performed
      using the SPSS v.10 to determine statistical differences in the MICs and the
      amplitude and frequency of spike bursts. Results were expressed as mean+/-SE
      (N=5). The MICs (microg/mL) of erythromycin (racemate), chiral isolate X, and
      chiral isolate Y were 0.45+/-0.29, 0.53+/-0.24 (n.s.), and 0.2+/-0.07
      (P<or=0.001), respectively. Erythromycin (racemate) at 10 mol/L, 10 mol/L, 5x10
      mol/L, 10 mol/L, and 10 mol/L concentrations caused the amplitude of spike bursts
      to increase by 18+/-7% (P=n.s.), 43+/-10% (P<or=0.05), 55+/-12% (P<or=0.001),
      121+/-23% (P<or=0.001), and 163+/-16% (P<or=0.001), respectively. The chiral
      isolate Y increased the amplitude of spike bursts at the same concentrations as
      tested above: 32+/-11% (P<or=0.05), 48+/-14% (P<or=0.001), 84+/-13% (P<or=0.001),
      112+/-18% (P<or=0.001), and 121+/-13% (P<or=0.001), respectively. Chiral isolate
      X caused much reduced effect on the amplitude of spike bursts: 9+/-6% (P=n.s.),
      27+/-12% (P=n.s.), 27+/-12% (P=n.s.), 30+/-11% (P=n.s.), and 30+/-11.2% (P=n.s.),
      respectively. EC50 for erythromycin (mixture) was 0.4x10 mol/L, and for
      erythromycin Y, it was 0.8x10 mol/L. The addition of erythromycin at 10 mol/L
      caused the frequency of spike bursts to increase 11+/-7% at 10 mol/L, 5x10 mol/L,
      10 mol/L, and 10 mol/L; the changes were 13+/-10% (P=n.s.), 13+/-10% (P=n.s.),
      22+/-13% (P=ns), and 39+/-30% (P<or=0.05), respectively. Chiral isolate Y of
      erythromycin, changed the frequency of spike bursts by 26+/-21% (P=n.s.); 35+/
      20% (P=n.s.), 39+/-30% (P=n.s.), 41+/-37% (P=n.s.), and 44+/-36% (P=n.s.) at the
      respective concentrations as discussed above. Chiral isolate X altered the
      frequency of spike bursts at the same concentrations as 40+/-30% (P=n.s.), 45+/
      30% (P=n.s.), 62+/-41% (P=n.s.), 62+/-41% (P=n.s.), and 52+/-35% (P=n.s.),
      respectively. Data indicate that erythromycin (racemate) and chiral isolates X
      and Y possess similar antibacterial activity. It was also shown that erythromycin
      and chiral isolate Y increase significantly the amplitude of spike bursts
      compared with baseline. Isolate X does not increase the amplitude of spike bursts
      in a dose-dependent manner. The frequency of spike bursts is not significantly
      changed in the presence of erythromycin or the 2 chiral isolates.

PMID- 16428923
TI  - Pharmacoenhancement of protease inhibitors.
AB  - Toxicity, adherence problems, and virological failure may limit treatment by
      protease inhibitor-containing regimens at standard doses. Addition of low-dose
      ritonavir results in a high plasma concentration of coadministered protease
      inhibitor resulting in decreased pill burden, a reduction in the number of doses,
      fewer food and/or fluid restrictions, and a higher rate of virological
      suppression. These effects are due to improved pharmacokinetics of coadministered
      protease inhibitors.

PMID- 16428924
TI  - Managing atherosclerosis in patients with type 2 diabetes mellitus and metabolic
      syndrome.
AB  - Diabetes mellitus with its increasing prevalence is a major global health problem
      in United States. Macrovascular complications, especially atherosclerosis, are
      the major cause of morbidity and mortality in patients with type 2 diabetes
      mellitus. Metabolic syndrome is considered to be a metabolic precursor of type 2
      diabetes mellitus and is an independent risk factor in the pathogenesis of
      atherosclerosis. It is a constellation of proatherogenic metabolic abnormalities,
      which include obesity, hypertension, characteristic dyslipidemia, hyperglycemia,
      insulin resistance, and compensatory hyperinsulinemia. Recent epidemiological
      data have demonstrated a strong causal association between insulin resistance and
      coronary vascular disease independent of hyperglycemia associated with type 2
      diabetes mellitus. Given the high prevalence of metabolic syndrome in the general
      population and its role in the pathogenesis of atherosclerosis, every attempt
      should be made to recognize early the metabolic syndrome and to modify the
      associated proatherogenic metabolic abnormalities. Management of atherosclerosis
      in insulin-resistant states like metabolic syndrome and type 2 diabetes is a
      multifactorial process involving nonpharmacological interventions like exercise,
      diet control, and pharmacological therapy directed at hypertension,
      hyperglycemia, and dyslipidemia. Further research is warranted to demonstrate the
      effects of these interventions unequivocally in preventing the progression of
      metabolic syndrome to overt type 2 diabetes mellitus with its associated
      macrovascular complications.

PMID- 16428925
TI  - The treatment of psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a chronic, autoimmune, seronegative inflammatory
      arthritis characterized by varying degrees of axial and peripheral arthritis.
      Here, we review the literature on the pharmacological management of PsA and
      present a simple treatment algorithm based on the available information. Although
      PsA management must be individualized to the degree and type of joint pain and
      inflammation, in general, nonsteroidal antiinflammatory drugs (NSAIDs) still
      represent first-line treatment of mild PsA. Second-line therapy includes older
      agents such as gold salts, methotrexate, sulfasalazine, and cyclosporine. The
      tumor necrosis factor alpha (TNF-alpha) antagonists represent the most recent
      major advance in the clinical management of PsA.

PMID- 16428926
TI  - N-acetylcysteine use in ischemic hepatitis.
AB  - We describe a case of antidepressant-induced ischemic hepatitis that responded to
      intravenous administration of N-acetylcysteine. Cytoprotection in the setting of
      ischemic hepatitis may be a therapeutic effect of N-acetylcysteine.

PMID- 16428927
TI  - Effectiveness of a treatment based on melatonin in five patients with systemic
      sclerosis.
AB  - Systemic sclerosis (SSc) is a multisystem connective disorder in which
      endothelial damage leads to fibrotic reactions through platelet
      hyperaggregability and inappropriate release of platelet-derived growth factors.
      With other colleagues, I have previously reported that melatonin seems to have a
      direct favorable effect on endothelium (stopping of bleeding symptoms in
      thrombocytopenic patients). Furthermore, melatonin has been described as
      performing an antiaggregating activity, and ACTH and vitamin E have been
      described as increasing melatonin effects. This provided the rationale to treat 5
      SSc patients with melatonin plus ACTH and vitamin E. Patients received the
      treatment for 1 month. The therapy was continued for 2 additional months in
      patients with stable or responding disease. After 3 months, the stable or
      responding patients continued the therapy for 2 months and longer. All patients
      had a partial response after 1 month. Continuing with the treatment, none of the
      5 patients had disease progression (average follow-up time of 16.6 months; range,
      7-44 months). Toxicity was lacking, with the only side effect being drowsiness.
      Our experience suggests that the combination of melatonin-ACTH-vitamin E may be
      safe and effective in patients with SSc.

PMID- 16428928
TI  - From total empiricism to a rational design of metronomic chemotherapy phase I
      dosing trials.
AB  - 'Metronomic chemotherapy' represents a novel anti-angiogenic strategy whereby low
      dose chemotherapy is utilized in a continuous fashion in order to target tumor
      endothelium. There are many potential advantages of this strategy and clinical
      trials are already underway. However, although the scheduling of metronomic
      chemotherapy is relatively unequivocal, metronomic dosing principles are at
      present poorly defined. Arbitrarily, 10-33% of the maximum tolerated dose
      comprises 'the dose range'. We argue that this is too empirical and propose a set
      of phase I metronomic chemotherapy dosing strategies based on a principled
      approach which may help to reduce the problem of empiricism in dosing for
      metronomic chemotherapy trials.

PMID- 16428930
TI  - Amifostine administration during radiotherapy for cancer patients with genetic,
      autoimmune, metabolic and other diseases.
AB  - Amifostine is a broad-spectrum cytoprotective agent approved for protection
      against cisplatin toxicities and radiation-induced xerostomia; strong clinical
      evidence exists that amifostine protects normal mucosa and lung from radiation
      damage. Hypotension, nausea/vomiting, fatigue and fever/rash are the main side
      effects associated with amifostine administration. The present study summarizes
      our experience on daily amifostine administration to cancer patients with various
      coexisting medical conditions and diseases. The tolerance and the eventual
      interference of amifostine with the course of the coexisting diseases is
      reported, providing a core list of medical conditions met in radiotherapy
      practice, their compatibility with amifostine administration and recommendations
      on how to deal with these patients. This list comprises genetic diseases
      (xeroderma pigmentosum, glucose-6-phosphate dehydrogenase deficiency), autoimmune
      disorders (vitiligo, scleroderma, thyroiditis, perforating collagenosis),
      metabolic diseases (diabetes mellitus), cardiovascular diseases,
      neuro/psychiatric diseases and other medical conditions (hypoglycemia, hepatic
      cirrhosis, alcoholism). A high incidence of fever/rash was noted in patients with
      autoimmune diseases, while all other conditions did not alter the patterns of
      side-effects expected following amifostine administration.

PMID- 16428929
TI  - Src tyrosine kinase as a chemotherapeutic target: is there a clinical case?
AB  - Src tyrosine kinase was the first protooncogene described. It has been found to
      be overexpressed and activated in a large number of different cancers. Cellular
      Src has been shown to activate a number of different effectors that are involved
      in different aspects of cancer biology such as metastasis, cell cycle regulation
      and cell survival. Despite this, Src inhibitors have not entered the regular
      arsenal of chemotherapeutics. This article reviews some of the biology,
      rationale, in vitro and in vivo preclinical evidence, and some very early
      clinical trials demonstrating efficacy of Src inhibitors.

PMID- 16428931
TI  - The Raf-1 pathway: a molecular target for treatment of select neuroendocrine
      tumors?
AB  - Neuroendocrine (NE) tumors such as medullary thyroid cancer, carcinoid, small
      cell lung cancer and pheochromocytoma are metastatic in nature, and secrete
      biogenic amines and hormones. In this review, we will discuss the possibility
      that activation of the Ras/Raf signaling pathway may be a therapeutic target for
      patients with select NE tumors. In-vitro activation of Raf-1 in NE tumors either
      by expression of the ectopic catalytic domain of Raf-1 or by a pharmacologic
      drug, ZM336372, resulted in growth inhibition. In addition, activation of the
      Ras/Raf pathway led to a significant reduction in NE markers such as serotonin,
      chromogranin A and calcitonin. These data support development of Raf-1-activating
      compounds for treatment of patients with NE tumors of selective subtypes.

PMID- 16428932
TI  - Anti-proliferative and anti-tumor effects of antisense oligonucleotide GTI-2601
      targeted against human thioredoxin.
AB  - Human thioredoxin has been implicated in cancer as a growth stimulator through
      regulation of DNA replication and growth factor activity, as a modulator of
      transcription factor activity, and as an inhibitor of apoptosis. In the present
      study, the steady-state level of thioredoxin protein was examined in a number of
      cancer cell lines. Interestingly, thioredoxin expression is elevated in a variety
      of human tumor cell lines compared with normal cell lines. The altered expression
      of thioredoxin in tumor cells suggests it may be a target in the development of
      novel therapeutic agents for the treatment and prevention of cancer. Further to
      this possibility, 26 phosphorothioate antisense oligodeoxynucleotides (PS-AS
      ODNs) were evaluated for the ability to inhibit thioredoxin expression in cell
      culture. One PS-AS-ODN, GTI-2601, specifically reduced the levels of thioredoxin
      mRNA and protein, exhibited potent anti-proliferative effects on colony formation
      in vitro, and had anti-tumor effects in human tumor xenograft mouse models in
      vivo. Sequence-specific decreases in thioredoxin expression levels were
      accompanied by significant suppression of tumor growth in mice. Taken together,
      these data suggest that thioredoxin may be a useful target for developing PS-AS
      ODNs as drug candidates against human cancer.

PMID- 16428933
TI  - Relationships between DNA strand breakage and apoptotic progression upon
      treatment of HL-60 leukemia cells with tafluposide or etoposide.
AB  - Tafluposide (F11782), an epipodophyllotoxin derivative currently undergoing phase
      I clinical trials, is structurally close to the established anti-cancer drug
      etoposide, but mechanistically distinct. It is a dual inhibitor of topoisomerases
      I and II which impairs the binding of the enzyme to DNA, but does not stabilize
      the cleavage complex. Nevertheless, both etoposide and tafluposide induce DNA
      strand breaks and are potent pro-apoptotic agents. In this study, we have
      compared the cellular response of HL-60 human promyelocytic leukemia cells
      treated with etoposide and tafluposide. We show that tafluposide induces delayed,
      but extensive, DNA strand breaks, whereas etoposide provokes rapid and massive
      DNA damage. The two drugs trigger similar types of alterations at the
      mitochondrial and cell cycle levels, and lead to the generation of comparable
      levels of reactive oxygen species, but with different kinetics. Our data suggest
      that modification of the mitochondrial mass plays an important role in apoptosis
      induced by DNA-damaging anti-cancer agents, at least in the epipodophyllotoxin
      series. We suggest that drug-induced mitochondrial alterations can be divided
      into three successive steps: (i) hyperpolarization, (ii) depolarization and (iii)
      increase of the mitochondrial mass.

PMID- 16428934
TI  - The combi-targeting concept: evidence for the formation of a novel inhibitor in
      vivo.
AB  - With the purpose of developing drugs that can block multiple targets in tumor
      cells, molecules termed combi-molecules or TZ-I have been designed to be
      hydrolyzed in vitro to TZ+I, where TZ is a DNA-damaging species and I is an
      inhibitor of the epidermal growth factor receptor (EGFR). Using HPLC and liquid
      chromatography-mass spectrometry (LC-MS), we investigated the mechanism of in
      vivo degradation of a prototype of one such combi-molecule, ZRBA1, which when
      administered i.p. rapidly degraded into FD105 (Cmax=50 micromol/l, after 30 min),
      a 6-aminoquinazoline that was N-acetylated to give FD105Ac (IAc) (Cmax=18
      micromol/l, after 4 h). A similar rate of acetylation was observed when
      independently synthesized FD105 was administered i.p. More importantly, the EGFR
      binding affinity of IAc was 3-fold greater than that of I, indicating that the
      latter is converted in vivo into an even more potent EGFR inhibitor. The results
      in toto suggest that while in vitro TZ-I is only hydrolyzed to I+TZ, further
      acetylation of I in vivo leads to a third component--a highly potent EGFR
      inhibitor with a delayed Cmax.

PMID- 16428935
TI  - Difference of cell cycle arrests induced by lidamycin in human breast cancer
      cells.
AB  - Lidamycin (LDM) is a member of the enediyne antibiotic family. It is undergoing
      phase I clinical trials in China as a potential chemotherapeutic agent. In the
      present study, we investigated the mechanism by which LDM induced cell cycle
      arrest in human breast cancer cells. The results showed that LDM induced G1
      arrest in p53 wild-type MCF-7 cells at low concentrations, and caused both G1 and
      G2/M arrests at higher concentrations. In contrast, LDM induced only G2/M arrest
      in p53-mutant MCF-7/DOX cells. Western blotting analysis indicated that LDM
      induced G1 and G2/M arrests in MCF-7 cells were associated with an increase of
      p53 and p21, and a decrease of phosphorylated retinoblastoma tumor suppressor
      protein, cyclin-dependent kinase (Cdk), Cdc2 and cyclin B1 protein levels.
      However, LDM-induced G2/M arrest in MCF-7/DOX cells was correlated with the
      reduction of cyclin B1 expression. Further study indicated that the
      downregulation of cyclin B1 by LDM in MCF-7 cells was associated with decreasing
      cyclin B1 mRNA levels and promoting protein degradation, whereas it was only due
      to inducing cyclin B1 protein degradation in MCF-7/DOX cells. In addition,
      activation of checkpoint kinases Chk1 or Chk2 maybe contributed to LDM-induced
      cell cycle arrest. Taken together, we provide the first evidence that LDM induces
      different cell cycle arrests in human breast cancer cells, which are dependent on
      drug concentration and p53 status. These findings are helpful in understanding
      the molecular anti-cancer mechanisms of LDM and support its clinical trials.

PMID- 16428936
TI  - Decrease in c-Myc activity enhances cancer cell sensitivity to vinblastine.
AB  - The c-myc oncogene encodes for a transcriptional factor involved in many cellular
      processes such as proliferation, differentiation and apoptosis. According to
      these different functions, the role of c-Myc protein in cellular sensitivity to
      anti-cancer drugs is controversial. We defined the role of c-Myc in cancer cell
      sensitivity to vinblastine (VLB) using human colon cancer cells: LoVo wild-type
      or transfected with a plasmid containing the human c-myc gene in antisense
      orientation (LoVo-mycANS). Analysis of VLB cytotoxicity demonstrated a 3-fold
      increase in VLB sensitivity in LoVo-mycANS cells. Comparison between cells
      revealed different apoptosis kinetics: accumulation of cells in sub-G1 phase and
      poly(ADP-ribose) polymerase cleavage occurred earlier in LoVo-mycANS. Then, we
      demonstrated a mitochondrial membrane potential disruption followed by cytochrome
      c release that indicates the involvement of mitochondria in this apoptotic
      signaling pathway. This earlier apoptosis was accompanied by a Bcl-2 decrease and
      a p53 increase. In conclusion, the decrease in c-Myc expression enhanced the VLB
      sensitivity, triggering earlier apoptosis through induction of the intrinsic
      pathway. Thus, c-myc induction is a resistance factor and our findings suggest
      that tumors carrying low levels of c-Myc protein could be more responsive to
      vinca alkaloids treatment. Moreover, the downregulation of c-myc oncogene by an
      antisense strategy might represent a useful goal for improving the efficacy of
      this anti-neoplastic drug family.

PMID- 16428937
TI  - Effect of Ukrain on matrix metalloproteinase-2 and Secreted Protein Acidic and
      Rich in Cysteine (SPARC) expression in human glioblastoma cells.
AB  - Glioblastoma is a highly malignant brain tumor with a highly invasive phenotype
      and hence an unfavorable prognosis even in response to multidisciplinary
      treatment strategies. Ukrain, a semi-synthetic thiophosphoric acid derivative of
      the purified alkaloid chelidonine, has been used in the therapy of several solid
      tumors, but little is known about its effect on glioblastoma and, in general,
      about the molecular mechanisms responsible for its effects. We used RT-PCR,
      Western blot and SDS-zymography to investigate the effects of three doses of
      Ukrain (0.1, 1 and 10 micromol/l) on the expression of genes and proteins
      involved in the extracellular matrix remodeling associated with tumor invasion in
      human cultured glioblastoma cells treated for 24, 48 and 72 h. We analyzed the
      expression of matrix metalloproteinase-2 and -9, the main mediators of
      glioblastoma invasiveness, and secreted protein acidic and rich in cysteine
      (SPARC), involved in the regulation of cell-matrix interactions. There was a
      significant, dose-related decrease of glioblastoma cell proliferation and a
      tendency to downregulation of SPARC at the protein level 72 h after 10 micromol/l
      Ukrain, suggesting the drug may be a useful therapeutic tool for brain tumors.

PMID- 16428938
TI  - Recombinant interleukin-2 pre-treatment increases anti-tumor response to
      paclitaxel by affecting lung P-glycoprotein expression on the Lewis lung
      carcinoma.
AB  - The aim of the present study was to examine modifications of anti-tumor activity
      and toxicity of paclitaxel (PLX) when given p.o. after recombinant interleukin-2
      (rIL-2) to Lewis lung carcinoma-bearing mice. PLX was given orally to mice at the
      dose of 15 mg/kg on day 8 and 30 mg/kg on day 15, either alone or after 16.5
      microg of rIL-2 given i.p. twice a day either 1 or 3 days before. The anti-tumor
      activity was higher and PLX hematological toxicity not increased if orally
      administered PLX was given after a 3-day rIL-2 pre-treatment rather than if given
      alone. Lung metastasis was significantly lower and s.c. tumors were smaller in
      the PLX+rIL-2 group than in the PLX or rIL-2 or non-treated groups. In addition,
      a decrease in lung P-glycoprotein expression (investigated by Western blot
      analysis) was observed 1 h after the last administration of rIL-2 on day 7.

PMID- 16428939
TI  - Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in
      nude mice bearing human tumor xenografts.
AB  - The oral anti-tumor activity of a novel platinum(IV) complex, coded as LA-12,
      with a bulky adamantylamine ligand was evaluated and compared with another
      platinum(IV) complex satraplatin. The human carcinoma xenografts of colon HCT116,
      prostate PC3, and ovarian A2780 and A2780/cisR (resistant to cisplatin) were used
      to evaluate the in-vivo anti-tumor activity. The daily x 5 repeated dose regimen
      in equimolar doses of LA-12 and satraplatin, administered in 2 cycles, was
      selected for this evaluation. All doses of LA-12 and satraplatin were
      significantly effective in comparison with the control. The activities of LA-12
      in all doses and all used tumor xenografts were higher than equimolar doses of
      satraplatin. The highest effect was reached with LA-12 at a dose of 60 mg/kg. The
      shapes of growth curves of ovarian carcinoma A2780 and its subline resistant to
      cisplatin after therapy with LA-12 were very similar. This shows that LA-12 is
      able to overcome resistance to cisplatin.

PMID- 16428940
TI  - Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients
      with head and neck cancer.
AB  - The goal of this study was to identify clinical characteristics and concurrent
      medications associated with an increased or decreased incidence of cisplatin
      induced nephrotoxicity. The medical records for 62 subjects with head and neck
      cancer who received cisplatin 100 mg/m2 (day 1) plus fluorouracil 1000 mg/m2
      (days 1-5) with or without radiation therapy were reviewed from three medical
      centers. The demographics, concurrent medication therapy, co-existing illnesses
      and clinical laboratory values were extracted from the medical records.
      Nephrotoxicity was defined as a minimum rise in serum creatinine of 0.5 mg/dl or
      above. The concurrent use of hydrochlorothiazide or multivitamins was associated
      with a higher incidence of nephrotoxicity after cycle 1. Use of albuterol,
      atenolol or hydrochlorothiazide was also associated with a higher incidence of
      nephrotoxicity after cycle 1 or 2. In contrast, subjects prescribed dexamethasone
      or ondansetron were less likely to experience nephrotoxicity. None of these
      medications affected treatment response. Race/ethnicity was independently
      correlated with the incidence of nephrotoxicity; African-American subjects were
      more likely to develop nephrotoxicity independent of the influence of these
      concurrent medications. Medications may modulate cisplatin-induced nephrotoxicity
      by altering the metabolic activation of cisplatin to a nephrotoxin. Genetic
      differences in the drug-metabolizing enzymes may contribute to the correlation
      with race. The results from this retrospective study provide data to support a
      larger prospective study to further investigate the associations between these
      concurrent medications and cisplatin-induced nephrotoxicity.

PMID- 16428941
TI  - A randomized, double-blind trial assessing the efficacy and safety of sublingual
      metopimazine and ondansetron in the prophylaxis of chemotherapy-induced delayed
      emesis.
AB  - The prevention of delayed emesis following chemotherapy remains an important
      challenge. This randomized, double-blind, double-dummy, multicenter study was
      designed to compare the efficacy and tolerance of metopimazine and ondansetron at
      preventing nausea and emesis in patients receiving chemotherapy. Two hundred
      patients were evaluated for efficacy: 103 patients received metopimazine (7.5 mg
      x 2 t.i.d.) and 97 received ondansetron (8 mg b.i.d.) for 5 days. Patients were
      asked to report episodes of nausea and emesis in a diary, and quality of life
      (QoL) was evaluated using the Functional Living Index--Emesis questionnaire. The
      incidence of complete response (defined as no nausea and emesis for 5 days) did
      not differ between the two treatment arms (53.4% for metopimazine versus 49.5%
      for ondansetron; P=0.58). No significant difference was found for the incidence
      of emesis (23.3% for metopimazine versus 30.9% for ondansetron) or QoL. Tolerance
      was as expected for both drugs and comparable, except for the incidence of
      gastrointestinal disorders, which was significantly lower in the metopimazine
      group (19.4 versus 32.7%; P=0.03). We conclude that metopimazine is an
      alternative to ondansetron that is better tolerated for the prevention of delayed
      emesis in patients receiving chemotherapy.

PMID- 16428942
TI  - Paclitaxel versus docetaxel for advanced gastric cancer: a randomized phase II
      trial in combination with infusional 5-fluorouracil.
AB  - Taxanes have clearly demonstrated activities against gastric cancer. We compared
      the combination of paclitaxel plus 5-fluorouracil (5-FU) (PF) with docetaxel plus
      5-FU (DF) as first-line chemotherapy in patients with measurable metastatic
      gastric cancer. Seventy-seven patients were randomly assigned to receive
      paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1, in combination with 5-FU 500
      mg/m2 continuous infusion on days 1-5. Treatment was repeated every 3 weeks. Of
      314 chemotherapy cycles delivered (median 5 in both groups), dose reduction was
      required more frequently in the DF group, being 9 and 19%, respectively (P<0.01).
      PF was associated with, although statistically insignificant, substantially less
      grade 3 or 4 toxicities than DF (68 versus 85%; P=0.09). Global quality of life
      was similar in both groups, but substantive differences in many symptom scores
      including pain, dyspnea, constipation and diarrhea favored PF. There were no
      significant differences in therapeutic efficacy between PF and DF with respect to
      response rate (42 versus 33%, respectively; P=0.53), and failure-free (3.6 versus
      4.2 months; P=0.92) and overall survival (9.9 versus 9.3 months; P=0.42). Both PF
      and DF appear to have efficacy against metastatic gastric cancer, with different,
      but acceptable, safety profiles.

PMID- 16428943
TI  - Phase II study of a 4-week capecitabine regimen in advanced or recurrent gastric
      cancer.
AB  - Our objective was to evaluate the efficacy and safety of capecitabine in
      chemotherapy-naive patients with unresectable advanced or metastatic gastric
      cancer. An open-label multicenter phase II study was conducted for previously
      untreated patients with advanced or metastatic gastric cancer. Oral capecitabine
      828 mg/m2 twice daily was given on days 1-21 every 4 weeks. Baseline
      characteristics of 60 enrolled patients were: male/female 49/11, median age 64
      years (range 28-74), good performance status (ECOG 0-1) in 98% of patients and 27
      patients had prior gastrectomy (45%). A median of 4 treatment cycles were
      administered (range 1-37). Five patients were excluded from the efficacy analysis
      because they did not meet eligibility criteria. The overall response rate (RR) in
      the evaluable patient population (n=55) was 26% [95% confidence interval (95% CI)
      15-39%] and a further 29% of patients had stable disease. The overall RR in the
      intent-to-treat population (n=60) was 23% (95% CI 13-36.0%). Median time to
      progression in the evaluable patient population was 3.4 months (95% CI 1.8-6.1)
      and overall survival time in the intent-to-treat population was 10.0 months (95%
      CI 6.4-13.6). The most frequent grade 3/4 drug-related adverse event was hand
      foot syndrome (13%), but this was readily managed by treatment interruption and
      dose reduction. No patients developed grade 3/4 drug-related diarrhea, vomiting,
      leukopenia or thrombocytopenia. We conclude that this 4-week regimen of
      capecitabine showed promising activity and was well tolerated as first-line
      therapy for advanced/metastatic gastric cancer. Further investigation of this
      regimen is warranted.

PMID- 16428944
TI  - Plasma levels of corticotroph-type pro-opiomelanocortin derivatives such as beta
      lipotropin, beta-endorphin(1-31), or adrenocorticotropic hormone are correlated
      with severity of postoperative pain.
AB  - BACKGROUND: In the pituitary of lower species, pro-opiomelanocortin is expressed
      in corticotroph cells of the anterior and in melanotroph cells of the
      neurointermediate lobe; enzymatic processing in the corticotrophs results in the
      release of adrenocorticotropic hormone, beta-lipotropin, or beta-endorphin. In
      the melanotrophs, these fragments are further modified, eg, by N-terminal
      acetylation. In the human pituitary, these enzyme systems are located within the
      same cells in the anterior lobe. We studied the reactions of the pro
      opiomelanocortin system under preoperative conditions as well as under
      postoperative pain. METHODS: In 17 patients undergoing hip or knee arthroplasty,
      we determined plasma concentrations of N-acetyl-beta-endorphin immunoreactive
      material, authentic beta-endorphin [beta-endorphin(1-31)], adrenocorticotropic
      hormone, beta-lipotropin immunoreactive material, and cortisol, as well as pain
      severity rated by the patients using a visual analogue scale before surgery,
      after surgery but still under spinal anesthesia, under postoperative pain, and 1
      day after surgery. RESULTS: Only low levels of N-acetyl-beta-endorphin
      immunoreactive material were measured in 16 out of 17 patients. High
      concentrations (1st quartile/median/3rd quartile; pmol/L) of adrenocorticotropic
      hormone (22.5/55.8/124) and beta-lipotropin immunoreactive material
      (6.6/34.6/142) were observed under postoperative pain, accompanied by a small
      increase of beta-endorphin(1-31) concentrations (0.0/6.1/10.9). Preoperatively
      small but significantly elevated levels of corticotroph-type and melanotroph-type
      pro-opiomelanocortin derivatives were observed; in contrast, spinal anesthesia
      suppressed all pro-opiomelanocortin fragment release. Postoperative pain severity
      correlated with postoperative adrenocorticotropic hormone, beta-lipotropin
      immunoreactive material, and beta-endorphin(1-31) concentrations. CONCLUSIONS: We
      conclude that the melanotroph-type pro-opiomelanocortin system is not activated
      under postoperative pain; the increase of corticotroph-type pro-opiomelanocortin
      fragment levels is different in quantity and proportion under preoperative
      conditions or postoperative pain, respectively.

PMID- 16428945
TI  - Judgments of pain in the neonatal intensive care setting: a survey of direct care
      staffs' perceptions of pain in infants at risk for neurological impairment.
AB  - OBJECTIVE: To determine whether healthcare professionals believe the pain of
      infants at risk for neurologic impairment differs from that of typical infants.
      SETTING: Neonatal intensive care units at 2 tertiary pediatric centers in Canada.
      PARTICIPANTS: Ninety-nine healthcare professionals who practice in the neonatal
      intensive care unit (51 nurses, 19 physicians, 18 respiratory therapists, 11
      other). MAJOR MEASURES: Participants completed the Pain Opinion Questionnaire. It
      elicits beliefs regarding the similarity of the pain experienced by infants at
      mild, moderate, and severe risk for neurologic impairment relative to those
      without risk for neurologic impairment along 5 pain facets (ie, sensation,
      emotional reaction, behavioral reaction, communication, incidence). RESULTS: Pain
      Opinion Questionnaire scores varied by level of risk of neurologic impairment
      (mild, moderate, severe) and pain facet. Respondents believed infants with risk
      were overall less likely to experience pain similar to infants without risk as
      the level of risk increased [F(2,97) = 66.0, P < 0.001] and were more likely to
      have a reduced pain experience relative to infants without risk as the level of
      risk increased [F(2,97) = 62.2, P < 0.001]. Pain Opinion Questionnaire scores did
      not vary due to profession, experience, gender, or age. CONCLUSION: Professionals
      expressed the belief that neurologically impaired infants' pain experience is
      reduced, relative to infants without impairment, as their level of risk for
      neurologic impairment increases. This belief did not vary due to professional
      experience or personal factors. Future studies should investigate the source of
      these beliefs and their impact on the pain management provided to infants with
      risk for neurologic impairment.

PMID- 16428946
TI  - Quantitative somatosensory testing of warm and heat-pain thresholds: the effect
      of body region and testing method.
AB  - OBJECTIVES: To study whether the sensitivity to noxious and innocuous heat varies
      across the body. METHODS: Heat-pain threshold and warm sensation threshold were
      measured in 20 patients, using the Method of Limits (MLI) and the Method of
      Levels (MLE) in 5 regions: the chest, forearm, mid thigh, and the dorsal surface
      of the hand and foot. RESULTS: With the Method of Limits, heat-pain threshold
      increased gradually from the lowest level in the chest (mean 42 degrees C) to
      peak level in the foot (44.5 degrees C, P < 0.001). With the Method of Levels,
      heat-pain threshold did not differ between body regions. Warm sensation
      thresholds measured with both Method of Limits and the Method of Levels was
      higher in the chest (36.2 degrees C) and foot (36.8 degrees C) compared to the
      other regions (mean of 35.3 degrees C, P < 0.01). The correlation between heat
      pain threshold and warm sensation threshold was low to moderate, depending on the
      tested region. Differences in heat-pain threshold and warm sensation threshold
      between the methods were highest in the legs and smallest in the chest. The
      correlation between the Method of Limits and Method of Levels was moderate for
      heat-pain threshold (0.57) and good for warm sensation threshold (0.71).
      DISCUSSION: The sensitivity to noxious heat is uniform across the body when
      measured with a reaction-time-free method (Method of Levels), but is greater in
      proximal than in distal regions, when measured with a reaction-time-dependent
      method (Method of Limits). Regardless of measuring method, the sensitivity to
      innocuous heat is not uniform across the body. It is concluded that the Method of
      Levels is preferred when heat-pain threshold is to be compared between body
      regions. For heat-pain threshold, within-patient comparisons can be made between
      each pair of regions tested. However, for warm sensation threshold, within
      patient comparisons should be conducted between contralateral symmetrical
      regions.

PMID- 16428947
TI  - Using opioids with persisting noncancer pain: a biopsychosocial perspective.
AB  - OBJECTIVE: Despite the growing use of opioids for persisting noncancer pain,
      evidence for their effectiveness is limited, especially in relation to functional
      outcomes. Guidelines have been developed for prescribers, but their utility is
      untested. This review examines the use of opioids in this population from a
      biopsychosocial perspective and makes a number of recommendations. DATA SOURCES:
      Published comparison studies and reviews of oral opioids in chronic noncancer
      pain, as well as 5 published guidelines for the prescription of opioids and
      systematic reviews of cognitive-behavioral pain management programs. METHODS:
      Outcomes of the opioid comparison studies were reviewed and compared to those
      achieved by pain management programs. CONCLUSIONS: The available evidence
      indicates that by themselves, oral opioids generally achieve only modest
      reductions in pain levels in patients with chronic noncancer pain. Functional
      outcomes are inconsistent across studies. There are questions about the timing of
      their use and patient selection. There are risks in trials of opioids only after
      other conservative interventions have been tried unsuccessfully. Also, in some
      patients, ongoing use of opioids risks repeated over-doing of pain-generating
      activities and reinforcing escape/avoidance responses that promote disability.
      These risks may be lessened by assessment of current use of pain self-management
      strategies among potential candidates for opioids. This offers advantages in
      promoting collaborative management of persisting pain as well as better pain and
      functional outcomes. In this view, opioids may be considered as one possible
      element of a management plan rather than the primary treatment.

PMID- 16428948
TI  - Content comparison of low back pain-specific measures based on the International
      Classification of Functioning, Disability and Health (ICF).
AB  - OBJECTIVES: The objective of this study was to compare the content covered by the
      North American Spine Society Lumbar Spine Outcome Assessment Instrument, the
      Oswestry Low Back Disability Questionnaire, and the Roland-Morris Disability
      Questionnaire based on the International Classification of Functioning,
      Disability and Health (ICF). METHODS: The linkage of items of the three measures
      to the ICF involved three steps, which were performed by two different health
      professionals and in which 10 different linking rules were applied. RESULTS: In
      the 48 items of the three instruments, a total of 123 concepts were identified
      and linked to the ICF. The concepts contained in the items were linked to 10 ICF
      categories of the component "body functions," 27 of the component "activities and
      participation," and 4 of the component "environmental factors." The estimated
      kappa coefficients ranged from 0.67 to 1.00. CONCLUSION: Comparison based on the
      ICF provides insight into both the breadth of health dimensions measured as well
      as the thoroughness and depth of measurement. Therefore, it can be a useful tool
      when selecting specific measures for a study. Compared with other types of
      qualitative review, the most important advantage of the content comparison of
      measures based on the ICF is the use of an external and independent reference to
      which all the instruments can be linked and by which all the instruments can be
      compared. The three back-specific measures are comparable, with their common
      focus on physical aspects of body functions and activities and participation.

PMID- 16428949
TI  - Patellofemoral pain syndrome: evaluation of location and intensity of pain.
AB  - OBJECTIVES: To identify the sites and intensity of pain in patients with
      patellofemoral pain syndrome. METHOD: A prospective cohort study was conducted at
      an academic sports medicine practice in Boston, Massachusetts. All patients met
      inclusion criteria and were enrolled and evaluated during the study time frame. A
      single sports medicine orthopaedic surgeon examined a consecutive sample of
      patients with patellofemoral pain not explained by one of several well-defined
      anterior knee pain diagnoses. The study group consisted of 100 patients (75
      females, 25 males) with median age of 14 years. Eleven discrete locations were
      palpated for tenderness. Hamstring tightness was evaluated by measuring the
      popliteal angle. Patients reported intensity of pain using a 0- to 9-point
      ordinal scale. Regression and nonparametric statistical methods were used.
      RESULTS: The most common site of pain was the patella during anterior-posterior
      compression (90 patients), followed by the distal pole of the patella, the medial
      plica, and the nonarticular medial femoral condyle. Median "worst pain" intensity
      was 6 out of a possible 9. The most common site of "worst pain" was also the
      patella in compression (63 patients). Median duration of symptoms was 10 months,
      with an interquartile range of 3 to 20 months. Pain intensity was inversely
      correlated with duration of symptoms (P < 0.01). CONCLUSIONS: In these patients
      with patellofemoral pain syndrome, the major source of pain was the patella
      subchondral bone.

PMID- 16428950
TI  - Psychological processes underlying the development of a chronic pain problem: a
      prospective study of the relationship between profiles of psychological variables
      in the fear-avoidance model and disability.
AB  - OBJECTIVES: Understanding the psychological processes that underlie the
      development of a chronic pain problem is important to improve prevention and
      treatment. The aim of this study was to test whether distinct profiles of
      variables within the fear-avoidance model could be identified and could be
      related to disability in a meaningful way. METHODS: In 81 persons with a
      musculoskeletal pain problem, cluster analysis was used to identify subgroups
      with similar patterns on fear and avoidance beliefs, catastrophizing, and
      depression. The clusters were examined cross-sectionally and prospectively on
      function, pain, health care usage, and sick leave. RESULTS: Five distinct
      profiles were found: pain-related fear, pain-related fear + depressed mood,
      medium pain-related fear, depressed mood, and low risk. These subgroups were
      clearly related to outcome. In contrast to the clusters "medium pain-related
      fear" and "low risk," the majority of those classified in the clusters "pain
      related fear," "pain-related fear + depressed mood," and "depressed mood"
      reported long-term sick leave during follow-up. The subjects in the clusters with
      high scores on the depression measure reported the highest percentage of health
      care usage during follow-up (70% in the "pain-related fear + depressed mood"
      group and 42% in the "depressed mood" group reported >10 health care visits).
      CONCLUSIONS: Distinct profiles of psychological functioning could be extracted
      and meaningfully related to future disability. These profiles give support to the
      fear-avoidance model and underscore the need to address the psychological aspects
      of the pain experience early on.

PMID- 16428951
TI  - High incidence of chronic pain following surgery for pelvic fracture.
AB  - OBJECTIVES: To determine the incidence of chronic pain after surgery for pelvic
      fracture using a strict definition and measures of intensity and health-related
      quality of life. METHODS: In April 2004, a questionnaire was sent to 221 patients
      who underwent surgery for pelvic fracture in the period 1996 to 2000. Chronic
      pain was defined as pain at present that related back to the pelvic fracture and
      was not a consequence of other disease. Health-related quality of life was
      measured using the 15D questionnaire. RESULTS: The response rate was 72.9% after
      a median follow-up of 5.6 years. Chronic pain was seen in 48.4% (95% confidence
      interval, 40.7%-56.2%). These patients had a combination of somatic nociceptive,
      visceral nociceptive, and neuropathic pain and had significantly lower health
      related quality of life. Also, the use of opioids (14.1% vs. 4.8%) and
      nonsteroidal anti-inflammatories/paracetamol (57.7% vs. 21.7%), the request for
      financial compensation (75.6% vs. 45.8%), and complications related to leg
      function (62.8% vs. 20.5%) were significantly higher in the group with chronic
      pain than in the group without chronic pain. CONCLUSIONS: Chronic pain after
      pelvic fracture is a major problem that affects a patient's quality of life. The
      use of analgesics was higher in these patients, and they had more complications.
      Chronic pain after surgery for pelvic fracture deserves more attention.

PMID- 16428952
TI  - Pain and aberrant drug-related behaviors in medically ill patients with and
      without histories of substance abuse.
AB  - OBJECTIVES: This study evaluated the prevalence and correlates of aberrant drug
      taking behaviors in two populations: patients with HIV-related pain and a history
      of substance abuse (n = 73) and patients with cancer pain and no history of
      substance abuse (n = 100). METHODS: All patients completed a Drug-Taking
      Behaviors Interview, the Brief Symptom Inventory (BSI), Brief Pain Inventory
      (BPI), Memorial Symptom Assessment Scale (MSAS), and the Marlowe Crowne Social
      Desirability Scale (MCSDS). The Pain Management Index was calculated to assess
      the adequacy of opioid prescribing. RESULTS: The cancer sample comprised 38 men
      and 62 women, and the AIDS sample comprised 63 men and 10 women. Patients with
      AIDS-related pain had higher global distress on the MSAS (F1, 170 = 20.05, P <
      0.001), greater pain-related interference in their daily functioning on the BPI
      (F1, 161 = 22.87, P < 0.001), and a lower percentage of relief from their current
      medications (F1, 156 = 76.14, P < 0.001). AIDS patients also reported more than
      twice as many examples of aberrant drug-related behaviors per patient (mean =
      6.14, SD = 4.60) as the cancer patients (mean = 1.42, SD = 1.91). CONCLUSION:
      These data suggest that AIDS patients with histories of substance abuse receiving
      opioid therapy are more symptomatic, have more distress, experience more
      interference from residual pain, and engage in more problematic drug-related
      behaviors than patients with no history of drug abuse receiving opioids for
      cancer pain. Treatment of substance abusers with pain requires skills that
      complement best practices in opioid prescribing. Better approaches to the long
      term treatment of these populations are needed.

PMID- 16428953
TI  - Percutaneous cement injection into a created cavity for the treatment of
      vertebral body fracture: preliminary results of a new vertebroplasty technique.
AB  - OBJECTIVES: Vertebral body fractures (VBFs) are the most common complication of
      osteoporosis. Minimally invasive placement of cement to stabilize VBFs results in
      significant pain reduction and improved performance of daily activities. The
      authors describe a modified percutaneous vertebroplasty (PV) procedure during
      which a cavity is created manually in the VBF, allowing the cement to be injected
      with less resistance. METHODS: Data were gathered from a retrospective chart
      review from 15 consecutive patients with acute compression VBFs who underwent 33
      PV procedures with the Cavity Creation System. Mean follow-up was 30 weeks. Oral
      opiate intake, quality of life improvement, and visual analog pain scores (VAS)
      were measured before and 1 month after the procedure. RESULTS: All 15 patients
      exhibited a reduction in pain VAS (mean reduction 5.9 +/- 2.5). Improvement in
      quality of life was demonstrated by lower (improved) FACIT scores in the General
      Activity, Enjoyment of Life, Mood, Normal Work Routine, and Sleep subscales. In
      addition, opioid use decreased in 10 of the 12 (83%) patients who were taking
      opioids before surgery. In eight (67%) patients, opioid use decreased by over
      50%. Complications included extrusion of cement in two patients (an incidence of
      5.7% of the levels operated) and two patients with intraoperative rib fractures.
      No postoperative neurologic deficits were noted. CONCLUSIONS: The Cavity Creation
      System is a safe, cost-effective treatment of VBF resulting in good/excellent
      pain relief and an improved quality of life.

PMID- 16428954
TI  - Treatment of chronic plantar fasciitis with Botulinum toxin A: preliminary
      clinical results.
AB  - Based on recent results in chronic lateral epicondylitis we decided to
      investigate the efficacy of Botulinum toxin A (BTX-A) for treatment of chronic
      therapy resistant plantar fasciitis. Nine patients with an average duration of
      symptoms of 14 months and at least two prior conservative treatments received a
      one injection of 200 units of BTX-A (Dysport) subfascially into the painful area.
      The patients documented pain at rest and during weight-bearing after 2, 6, 10 and
      14 weeks by a visual analogue scale. A significant reduction of pain during
      weight-bearing to about 50% was seen 6 weeks after injection. The effect was
      still present at the latest follow-up of 14 weeks. Similarly, the pain at rest
      was reduced to less than half of the initial value at any follow-up. All patients
      were satisfied and did not require further treatment.

PMID- 16428955
TI  - Warning headache of subarachnoid hemorrhage and infarction due to vertebrobasilar
      artery dissection.
AB  - OBJECTIVES: The authors describe the clinical features of headache in patients
      with vertebrobasilar artery dissection (VBAD) and emphasize the importance of
      recognition of warning headaches preceding subarachnoid hemorrhage. Headache in
      VBAD is already recognized, but the natural history and clinical features of the
      warning headache have not been well elucidated. METHODS: The clinical features of
      30 patients with VBAD were analyzed retrospectively. RESULTS: Of the 30 VBAD
      patients, 16 presented with subarachnoid hemorrhage and 14 with ischemia.
      Headache (without any other symptoms or signs) was detected in 70% of patients
      with subarachnoid hemorrhage and 50% of patients with infarction. The headache
      started acutely, was localized to the occiput or nape of the neck, was sharp and
      severe in intensity, and was different from any previously experienced headaches.
      The interval from onset of headache to diagnosis of subarachnoid hemorrhage or
      infarction was 1 to 10 days. Three patients had sudden severe warning headaches
      without any evidence of subarachnoid hemorrhage at initial presentation and
      deteriorated within 24 hours due to subarachnoid hemorrhage, demonstrated later
      on computed tomography. Angiographic findings of patients with warning headaches
      were nonspecific compared with those of patients without headache. CONCLUSIONS:
      The present study confirms a high frequency of headache in patients with VBAD.
      Sudden severe occipital and nuchal pain, even without subarachnoid hemorrhage or
      any neurologic deficit, should be considered as a warning sign of subarachnoid
      hemorrhage. Computed tomography, magnetic resonance imaging, and magnetic
      resonance angiography should be performed urgently for screening of patients with
      a warning headache to prevent resultant life-threatening major vascular events.

PMID- 16428956
TI  - Fear-avoidance beliefs as measured by the fear-avoidance beliefs questionnaire:
      change in fear-avoidance beliefs questionnaire is predictive of change in self
      report of disability and pain intensity for patients with acute low back pain.
AB  - OBJECTIVES: The purposes of this study were to investigate the association among
      measures of fear-avoidance beliefs, pain intensity, and lumbar flexion and to
      determine if changes in these measures were predictive of treatment outcome
      following physical therapy for acute low back pain. It was hypothesized that
      items of the Fear-Avoidance Beliefs Questionnaire would be correlated with
      concurrent measures of pain intensity and lumbar flexion. In addition, it was
      hypothesized that changes in fear-avoidance beliefs would be predictive of
      changes in self-report of pain intensity and disability. STUDY DESIGN: Patients
      underwent a standard examination that included measures of fear-avoidance
      beliefs, pain intensity, lumbar flexion, and disability from low back pain.
      Patients were then re-examined after 4 weeks of physical therapy treatment.
      PATIENTS: Sixty-three patients with acute low back pain enrolled in a clinical
      trial of physical therapy treatment. RESULTS: Fear-Avoidance Beliefs
      Questionnaire items were consistently correlated with lumbar flexion, but not
      with measures of pain intensity. Pearson correlations indicated that changes in
      disability were significantly associated with changes in fear-avoidance beliefs
      and pain intensity, but not changes in lumbar flexion. Changes in fear-avoidance
      beliefs explained significant amounts of variance in changes in average pain
      intensity while controlling for changes in lumbar flexion. Changes in fear
      avoidance beliefs explained significant amounts of variance in changes in
      disability while controlling for changes in average pain intensity. CONCLUSIONS:
      These results suggest that fear-avoidance beliefs have a similar association with
      pain intensity, physical impairment, and disability for patients with acute and
      chronic low back pain. This study provides preliminary support for the use of the
      Fear-Avoidance Beliefs Questionnaire as an outcome measure for patients with
      acute low back pain.

PMID- 16428957
TI  - Direct comparison of placebo effects on clinical and experimental pain.
AB  - OBJECTIVES: Placebo effects have been suggested to be more potent on clinical
      than experimental pain. However, this proposition is based on the comparison of
      the magnitude of placebo analgesia between studies using different methodologies
      or between different groups of subjects within the same study. The authors sought
      to provide a more direct test of this hypothesis using a within-subject design
      and to investigate the potential mediating effect of expectancy. METHOD: Sixteen
      patients with low back pain rated the intensity and the unpleasantness of their
      clinical pain and underwent two cold pressor tests, both before and after a
      saline injection presented either as a potent painkiller (placebo treatment) in
      one session or as an inactive substance in a control session. RESULTS: The
      placebo treatment produced comparable increases in expected relief for clinical
      and experimental pain. However, ratings of pain intensity, pain unpleasantness,
      and perceived relief confirmed the larger placebo effect in low back pain than
      cold pressor pain. Retrospective ratings of perceived relief in low back pain
      generally showed the largest placebo effect compared with concurrent pain
      ratings. Furthermore, when the placebo session was performed after the control
      session, the placebo effect on low back pain was substantially reduced and
      observed only in perceived relief. Variations in expectation could not account
      for the large difference in placebo analgesia between clinical and experimental
      pain. CONCLUSIONS: The important reduction in placebo analgesia in low back pain
      after the single pre-exposure to the ineffective control treatment suggests the
      additional involvement of highly flexible mechanisms that may counteract the pro
      analgesic effects of expectations.

PMID- 16428958
TI  - Prognostic factors for duration of sickness absence due to musculoskeletal
      disorders.
AB  - OBJECTIVE: The purpose of this prospective cohort study with 1-year follow-up was
      to determine prognostic factors for duration of sickness absence due to
      musculoskeletal disorders. METHODS: Workers were included when on sickness
      absence of 2 to 6 weeks due to musculoskeletal disorders. A self-administered
      questionnaire was used to collect personal and work-related factors, pain,
      functional disability, and general health perceptions. Statistical analysis was
      done with Cox proportional hazard regression with an interaction variable with
      time for every risk factor of interest. Univariate and multivariate analyses were
      performed on musculoskeletal disorders and, separately, for low back pain.
      RESULTS: The main factors that were associated with longer sickness absence were
      older age, gender, perceived physical workload, and poorer general health for
      neck, shoulder and upper extremity disorders, and functional disability,
      sciatica, worker's own perception of the ability of return to work, and chronic
      complaints for low back pain. Workers with a high perceived physical work load
      returned to work increasingly slower over time than expected, whereas workers
      with a high functional disability returned to work increasingly faster over time.
      CONCLUSIONS: High pain intensity is a major prognostic factor for duration of
      sickness absence, especially in low back pain. The different disease-specific
      risk profiles for prolonged sickness absence indicate that low back pain and
      upper extremity disorders need different approaches when applying intervention
      strategies with the aim of early return to work. The interaction of perceived
      physical workload with time suggests that perceived physical workload would
      increasingly hamper return to work and, hence, supports the need for workplace
      interventions among workers off work for prolonged periods.

PMID- 16428959
TI  - Intravenous regional block with lidocaine for treatment of complex regional pain
      syndrome.
AB  - OBJECTIVES: The goal of this article is to report the successful treatment of a
      patient with complex regional pain syndrome (CRPS) type 1 involving the hand with
      the use of an intravenous regional block. METHODS: The patient was a 35-year-old
      woman who developed CRPS during conservative therapy for a metacarpal fracture.
      An intravenous regional block with lidocaine alone, using a two-tourniquet
      technique, was delivered 10 times for at least 40 minutes. The first five
      treatments were given twice a week and the next five were delivered weekly. All
      affected joints, including the wrist, were manipulated without undue force.
      Functional physical measurements were assessed, including range of motion and
      performance of fine and gross motor tasks. RESULTS: The visual analog scale
      scores for pain declined from 10 to 0 after treatment. Use of a pen, a pair of
      chopsticks, and a hammer improved, and edema decreased. CONCLUSIONS: Intravenous
      regional block with lidocaine was well tolerated and associated with relief in
      this case of CRPS type 1.

PMID- 16428961
TI  - Mad cow disease: documented cases in North America.

PMID- 16428962
TI  - Bariatric surgery: new policy for coverage proposed for Medicare recipients.

PMID- 16428964
TI  - Wellness as a self-care philosophy for nurses and their leaders.

PMID- 16428965
TI  - Lowering the risks of diabetes, hypertension, and heart disease.
AB  - Review care specifics for prediabetes, including details of hypertension and
      metabolic syndrome.

PMID- 16428967
TI  - The holistic nurse's search for credibility.
AB  - This article, part of a larger qualitative naturalistic study, examined what
      motivates professional RNs to become certified holistic nurses and the knowledge,
      skills, and attitudes holistic nurses perceive they need to become competent
      practitioners. Two key findings were (1) disjuncture between the traditional
      nursing structure and the nurses' own personal and professional growth and
      development and (2) the need for credibility. For these participants, obtaining
      the HNC credential conveyed credibility and legitimacy.

PMID- 16428968
TI  - Documenting health promotion services in community-based nursing centers.
AB  - A data-collection tool developed to document health promotion services and
      describe program participants was used by 7 community-based nursing centers for
      12 months. Data analysis results found that a wide range of services were offered
      to target populations across the life span, with adults aged 60 and older being
      the largest group of program users.

PMID- 16428969
TI  - An exploration of spirituality in rural women with chronic illness.
AB  - The purpose of this study was to explore expressions of spirituality in rural
      women with chronic illness. Six categories that emerged were prayer, faith,
      verse, finding meaning, transcendence, and family. Results of this study were
      consistent with findings in previous literature that spirituality can be an
      extremely helpful and powerful coping mechanism that can be used in managing the
      stressors of a chronic illness. Spirituality is an important illness management
      tool that needs to be acknowledged by healthcare professionals.

PMID- 16428970
TI  - Family presence during resuscitation.
AB  - Are policies allowing family into the trauma room humane and necessary--or just
      asking for trouble?

PMID- 16428971
TI  - What to do until the music therapist arrives? Developing therapeutic activities
      using music.
AB  - Three clinical vignettes describe appropriate and inappropriate uses of music as
      therapy for hospitalized patients.

PMID- 16428972
TI  - Patients' perceptions of spirituality and the nurse as a spiritual care provider.
AB  - This qualitative study explored patients' perceptions of spirituality and of the
      nurse as a spiritual care provider. Semistructured interviews were conducted with
      8 adults older than 21, who were living at home, and had been discharged from the
      hospital within the past 3 months having had at least a 5-day length of stay.
      Participants agreed that during their hospitalization, nurses were kind and
      caring but these behaviors were not perceived as spiritual care. Study findings
      suggest that patients do not perceive spiritual care within the role of nursing
      and therefore they did not share their spiritual concerns with nurses. Study
      findings are limited by sample size; however, implications for practice are that
      nurses need to be aware of a patient's spiritual needs to provide spiritual care.

PMID- 16428973
TI  - Helping patients with heart failure manage stress.

PMID- 16428974
TI  - Advances in clinical 3-tesla neuroimaging.
AB  - Three-tesla magnetic resonance (MR) imaging represents one of the major
      forefronts of diagnostic neuroradiology today. Heat deposition, changes in T1
      relaxation rates, susceptibility differences, and greater inherent sensitivity to
      motion artifacts represent challenges to clinical implementation. However, the
      situation appears remarkably similar to that encountered almost 15 years ago as
      the field of MR transitioned from 0.3-0.6 T to 1.5 T units. Current-generation 3
      T MR units already provide markedly improved imaging of the brain as compared
      with 1.5 T units. This is illustrated in the article that follows, together with
      many of the advanced techniques now available and in the pipeline to deal with
      the difficulties inherent at 3 T.

PMID- 16428975
TI  - T1-weighted imaging of the brain at 3 tesla using a 2-dimensional spoiled
      gradient echo technique.
AB  - RATIONALE AND OBJECTIVES: The objective of this study was to evaluate a 2
      dimensional spoiled gradient echo (GRE) imaging approach using a very short in
      phase TE for routine T1-weighted imaging of the brain at 3 T. MATERIALS AND
      METHODS: Patient examinations were compared from a 3 T magnetic resonance (MR)
      unit located immediately adjacent to a similarly equipped 1.5 T unit. Pre- and
      postcontrast T1-weighted images were evaluated and compared at 1.5 versus 3 T
      with a 2-dimensional (2-D) spin echo sequence used at 1.5 T and a 2-D GRE
      sequence at 3 T. The 2 MR systems used are from the same vendor, use similar 8
      channel coils, and use identical gradients. The T1-weighted GRE sequence, used at
      3 T, relies on a short TE (2.4 ms) to limit flow-related and susceptibility
      artifacts. Region-of-interest analysis was performed on 16 different sagittal
      patient examinations at both field strengths (32 total) and similarly on 10
      different pre- and postcontrast axial examinations (40 total). Four blinded
      neuroradiologists also evaluated these studies. RESULTS: Using an off-midline
      sagittal slice depicting the caudate nucleus (signal-to-noise ratio [SNR] 163 +/-
      28 vs. 70 +/- 7, 3 T vs. 1.5 T) and corona radiata (SNR 214 +/- 35 vs. 82 +/-
      10), 3 T markedly outperformed 1.5 T in both SNR and contrast-to-noise ratio
      (CNR) (51 +/- 14 vs. 12 +/- 5). On axial imaging, despite a reduction in slice
      thickness (5 to 3 mm) and scan time (5 to 1 minute), there was no significant
      difference pre- or postcontrast in SNR and CNR comparing 3 and 1.5 T. On blinded
      film review, 3 T performed slightly better on sagittal scans than 1.5 T in regard
      to motion artifacts (reduced), gray-white matter differentiation, and overall
      image quality. On axial scans, 3 T performed markedly better in all 3 categories
      both pre- and postcontrast. In regard to overall image quality, 3 T was preferred
      9:2 precontrast and 4:1 postcontrast. CONCLUSIONS: High-quality, thin-section (3
      mm) T1-weighted imaging can be readily performed at 3 T using a short TE 2-D GRE
      technique. This approach offers superior SNR and CNR with reduced motion
      artifacts and scan time as compared with imaging at 1.5 T and is advocated for
      routine brain imaging at 3 T. It is robust (used in over 1500 patients to date)
      and does not experience significant specific absorption ratio limitations, poor
      tissue contrast, or accentuated motion artifacts like encountered with spin echo
      T1-weighted imaging at 3 T.

PMID- 16428976
TI  - Magnetic resonance imaging at 3.0 tesla detects more lesions in acute optic
      neuritis than at 1.5 tesla.
AB  - OBJECTIVE: We sought to assess whether magnetic resonance imaging (MRI) at 3.0 T
      detects more brain lesions in acute optic neuritis (ON) than MRI at 1.5 T.
      MATERIALS AND METHODS: Twenty-eight patients with acute ON were scanned at both
      field-strengths using fast-fluid-attenuated inversion recovery (FLAIR), proton
      density and T2-weighted turbo spin echo, and T1-weighted spin echo after
      contrast. In addition, magnetization-prepared rapid acquisition gradient echo
      (MPRAGE) was obtained after contrast at 3.0 T. Lesion number and volumes were
      assessed by an observer blind to patient identity and field strength. RESULTS:
      Scans at 3.0 T showed a significantly increase in number of lesions detected on
      FLAIR images (P = 0.002) relative to scanning at 1.5 T. MPRAGE proved to be
      suitable for detecting enhancing lesions in ON. CONCLUSION: The MRI protocol at
      3.0 T was more sensitive to hyperintense brain lesions in ON than the standard
      MRI protocol at 1.5 T.

PMID- 16428977
TI  - Fast and quantitative high-resolution magnetic resonance imaging of the optic
      nerve at 3.0 tesla.
AB  - A novel and fast magnetic resonance imaging approach for imaging the optic nerve
      and the surrounding cerebrospinal fluid sheath is presented. The method provides
      high contrast between the nerve and cerebrospinal fluid and allows for accurate
      quantification of the optic nerve and its cerebrospinal fluid sheath diameter
      within 1.5 seconds scan time. Results of a volunteer study illustrate that
      measurements can reliably be performed even in the distal part of the
      intraorbital optic nerve track. Accuracy of quantification of the new technique
      is demonstrated by the assessment of changes in the optic nerve and CSF sheath
      diameter between straight gaze and 30 degrees abduction.

PMID- 16428978
TI  - Activation of cortical and subcortical auditory structures at 3 T by means of a
      functional magnetic resonance imaging paradigm suitable for clinical use.
AB  - OBJECTIVES: Visualization of functional magnetic resonance imaging (fMRI)
      activation of subcortical auditory structures remains challenging because of the
      cardiac-related pulsatile movement of both the brainstem and the cerebrospinal
      fluid and involved, until now, special scanning, pre- and postprocessing
      techniques, which are not convenient in clinical settings. The aim of this study
      is to examine the activation in both cortical and subcortical auditory structures
      by means of an fMRI paradigm, which is suitable for clinical use. MATERIALS AND
      METHODS: Twenty subjects (13 volunteers and 7 patients) were examined on a 3 T
      imaging system with binaural musical stimulation. RESULTS: Both cortical and
      subcortical auditory structures are successfully visualized in volunteers and
      patients. CONCLUSIONS: Activation of both the cortical and subcortical auditory
      structures can be visualized by means of an appropriate fMRI setup at 3 T. This
      paradigm can easily be used in patients with tumors and/or hearing disorders.

PMID- 16428979
TI  - Effect of field strengths on magnetic resonance angiography: comparison of an
      ultrasmall superparamagnetic iron oxide blood-pool contrast agent and
      gadopentetate dimeglumine in rabbits at 1.5 and 3.0 tesla.
AB  - OBJECTIVES: We sought to compare the intravascular enhancement of an ultrasmall
      superparamagnetic iron oxide (USPIO) blood-pool contrast agent to gadopentetate
      dimeglumine for contrast-enhanced magnetic resonance angiography (CE-MRA) at
      field strengths of 1.5 and 3.0 T in rabbits. MATERIALS AND METHODS: CE-MRA at 1.5
      and 3.0 T was performed at several time points (50 seconds and 5, 10, 20, and 30
      minutes) after the manual intravenous injection of 40 micromol Fe/kg body weight
      of an USPIO (SH U 555 C; Schering AG, Berlin, Germany) and 100 micromol/kg body
      weight gadopentetate dimeglumine (Magnevist; Schering AG, Berlin, Germany). MRA
      was performed with comparable acquisition parameters at both field strengths
      (Turbo-gradient sequence; 1.5 T: TR/TE/alpha: 5.5/1.7 milliseconds/40 degrees ;
      3.0 T: TR/TE/alpha: 5.1/1.8 milliseconds/40 degrees ) on clinical imaging systems
      (both: Gyroscan Intera, Philips Medical Systems, Best, The Netherlands). At
      either field strength, 6 rabbits were studied with both contrast agents (n = 24
      in total). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were
      calculated from signal intensity measurements in the abdominal aorta. RESULTS:
      Compared with 1.5 T, the SNR and CNR of gadopentetate dimeglumine significantly
      increased at 3.0 T by a factor of 2.2 and 2.3, respectively (P <or= 0.01),
      measured 50 seconds after intravenous injection. SNR and CNR of SH U 555 C,
      measured 50 seconds after intravenous injection, did not change significantly
      with increasing field strength (P >or= 0.05). At both field strength and either
      time point, CNR and SNR of SH U 555 C were significantly higher compared with
      gadopentetate dimeglumine at 3.0 T (P <or= 0.01). CONCLUSIONS: SNR and CNR of
      gadopentetate dimeglumine significantly increased with increasing field strength.
      No SNR or CNR gain was observed for SH U 555 C. However, blood-pool MRA with SH U
      555 C is feasible at 3.0 T. Compared with gadopentetate dimeglumine, SNR and CNR
      of SH U 555 C were significantly higher from 5 to 30 minutes at both field
      strengths (P <or= 0.01).

PMID- 16428980
TI  - Spontaneous acute dissection of the internal carotid artery: high-resolution
      magnetic resonance imaging at 3.0 tesla with a dedicated surface coil.
AB  - PURPOSE: Magnetic Resonance Imaging (MRI) has become the method of choice in the
      evaluation of patients with suspected cervical artery dissection (CAD). However,
      reliable identification of acute CAD might be impaired by the limited spatial
      resolution of standard 1.5 T MRI. In this preliminary study, we implemented a
      multicontrast high-resolution noninvasive vessel wall imaging approach at 3.0 T
      in patients with spontaneous CAD. METHODS AND MATERIALS: Ten patients with CAD of
      the internal carotid artery (ICA) were included in the study. 3.0 T MRI (Gyroscan
      Intera, Philips) was acquired using a dedicated phased-array coil. MRI-protocol
      consisted of: (1) bright blood 3D inflow MRA (TR/TE/FA = 25 milliseconds/3.1
      millisecond/16 degrees , 120 slices, reconstructed voxel size 0.3 x 0.3 x 0.8
      mm); (2) black blood cardiac-gated water-selective T1w 3D spoiled GE (TR/TE/FA =
      31 milliseconds/7.7 milliseconds/15 degrees , 36 slices, 0.3 x 0.3 x 1.0 mm); and
      (3) black blood cardiac triggered fat suppressed T2w TSE (TR/TE/ETL = 3 heart
      beats/44 milliseconds/7, 18 slices, 0.3 x 0.3 x 2 mm). Three observers in
      consensus performed image analysis. Special attention was paid to the integrity
      of the luminal and adventitial vessel boundary and the presence of a
      communicating intimal tear or flap. RESULTS: 3.0 T MRI provided excellent
      delineation of vessel lumen and vessel wall as a result of the nearly complete
      suppression of arterial blood signal. An intramural hematoma could be identified
      in all patients, confined between the luminal and adventitial vessel boundary. In
      no patient a communicating intimal tear could be identified. Clear distinction
      between intramural hematoma and thrombus was possible. CONCLUSION: High
      resolution vessel wall imaging in patients with acute CAD is feasible. The
      increased signal-to-noise ratio at 3.0 T can be invested to obtain a higher
      spatial resolution, permitting depiction of intimal and adventitial vessel wall
      boundary and the intramural hematoma in the diseased vessel segment. The
      morphologic information that is gained is helpful in the understanding of the
      underlying pathomechanismen of CAD.

PMID- 16428981
TI  - Vulnerable plaque detection by 3.0 tesla magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: A clinical case report is presented on a 76-year-old
      man who volunteered for a 3.0 T magnetic resonance (MR) carotid protocol. The
      subject was referred for carotid endarterectomy and histology was performed on
      the ex vivo specimen and compared with the in vivo images. METHODS: The 3.0 and
      1.5 T (obtained for comparison) MR protocol consisted of 2-dimensional (2D) and 3
      dimensional (3D) multicontrast bright and black blood imaging for detecting the
      lumen and vessel wall. RESULTS: The combination of multicontrast black blood
      transverse images and the 3D time of flight transverse images provided
      visualization of a narrowed internal carotid artery lumen 4 mm above of the
      bifurcation and the presence of a complex atherosclerotic plaque containing a
      large lipid pool, calcification, and intact fibrous cap. Quantitative comparisons
      including vessel lumen and plaque area, signal-to-noise (SNR) and contrast-to
      noise (CNR) ratios were obtained for 1.5 and 3.0 T image data. Plaque composition
      was verified with histology. Macrophages were also detected in the shoulders of
      the plaque as demonstrated by CD68 staining and corresponded with a small
      hyperintense area in the T2W images at 3.0 T, but not observed in comparable 1.5
      T images. CONCLUSIONS: High field 3.0 T multicontrast MRI of atherosclerotic
      plaque has been validated with histology comparison and provides improved
      detection of complex atherosclerotic plaque with increased SNR and CNR compared
      with 1.5 T. Further studies validating contrast mechanisms of plaque at 3.0 T are
      required, but atherosclerotic plaque imaging has clear benefit from application
      at the higher magnetic field strength.

PMID- 16428982
TI  - Time-resolved contrast enhanced magnetic resonance angiography of the head and
      neck at 3.0 tesla: initial results.
AB  - OBJECTIVES: We sought to implement and evaluate a high-performance, extended
      field of view protocol for time-resolved contrast-enhanced magnetic resonance
      imaging (CEMRA) of the carotid circulation by using a dedicated neurovascular
      (NV) array coil. MATERIALS AND METHODS: A total of 16 adult volunteers and 20
      clinical patients with suspected cerebrovascular disease (15 male, 21 female, 25
      82 years of age) were scanned with a fast 3D MRA sequence (TR/TE: 2.16/1
      milliseconds, sampling BW: 1090 Hz/pixel), with echo-sharing and parallel
      acquisition. All studies were performed on a 3.0 T MR system using an 8-channel
      neurovascular array coil. After injection of 6 mL of gadodiamide at 3 mL/s, a
      coronal 3D data set with in-plane resolution of 1 x 1.3 was implemented for 10
      consecutive measurements each 1.8 seconds apart. The subjects subsequently
      underwent high spatial-resolution (in-plane: 0.8 x 0.9) CEMRA for comparative
      analysis. The quality of segmental arterial anatomy and the presence and degree
      of the arterial stenosis were evaluated by 2 neuroradiologists. The interobserver
      variability was tested by kappa statistics and comparative analysis between the
      TR-CEMRA and high spatial-resolution CEMRA was evaluated by mean of the Spearman
      rank correlation coefficient. RESULTS: Craniocervical arteries were visualized
      with good image quality and definition in the diagnostic range. Occlusive disease
      was detected in 42 (reader A) and 44 (reader B) arterial segments with excellent
      interobserver agreement (kappa =0.89; 95% confidence interval 0.82-0.96). There
      was a significant correlation between the TR-CEMRA and high spatial-resolution
      CEMRA (Rs = 0.91 and 0.93, for readers A and B, respectively) for the degree of
      stenosis. Three aneurysms, 3 AVMs, 1 AV-fistula, and 2 subclavian steals were
      detected by both observers and were confirmed by correlative imaging. CONCLUSION:
      Time-resolved CEMRA at 3.0 T is reliable and versatile, providing 3-dimensional
      time-resolved data sets with high spatial (in plane: 1.3 x 1 mm2) and temporal
      (1.8 seconds) resolution over a large field of view. The higher signal-to-noise
      ratio gain at 3.0 T can be used effectively to improve performance of fast
      imaging and to support aggressive parallel acquisition protocols, as in the
      present study. Further clinical studies are required to establish the range of
      applications and the accuracy of the technique.

PMID- 16428984
TI  - Analysis of cardiac function--comparison between 1.5 Tesla and 3.0 Tesla cardiac
      cine magnetic resonance imaging: preliminary experience.
AB  - PURPOSE: We sought to assess the feasibility of magnetic resonance imaging to
      evaluate cardiac function at 3.0 T compared with 1.5 T. MATERIAL AND METHODS: In
      a prospective intraindividual comparative study, 12 volunteers (range, 18-54
      years), and 2 patients (range, 43-53 years) underwent cardiac cine magnetic
      resonance at both 3.0 T and 1.5 T. Data were acquired both with a steady-state
      free precession sequence (SSFP) and a spoiled gradient echo (SGE) sequence. If
      necessary, a frequency scout was used to correct for off-resonance artifacts. For
      both SSFP and SGE imaging, 6-mm thick retrospectively EKG-gated short axis views
      were acquired with equal matrix size (192 x 163) and comparable repetition time
      (TR). Cardiac function parameters were determined manually by a single
      investigator. Cardiac function parameters, signal to noise ratio (SNR), contrast
      to noise ratio (CNR), and the presence of artifacts were compared between the 2
      magnetic field strengths. For statistical analysis, a Pearson's correlation
      coefficient was calculated, and a paired Student t test was used to test
      statistical significance. RESULTS: Very good correlations between cardiac
      function parameters at 1.5 T and 3.0 T (r > 0.84, P < 0.0011) were obtained.
      Compared with SGE, SSFP more frequently was prone to artifacts. With SSFP/SGE at
      3.0 T, a SNR gain of 9.4/16% was achieved compared with 1.5 T. CONCLUSION:
      Functional cardiac cine magnetic resonance imaging can be regarded as equally
      accurate at 3.0 T compared with 1.5 T. Compared with SSFP imaging, the SGE
      sequence benefits more from higher field strengths and is less affected by
      artifacts.

PMID- 16428983
TI  - High-resolution magnetic resonance angiography of the renal arteries using
      parallel imaging acquisition techniques at 3.0 T: initial experience.
AB  - OBJECTIVE: The purpose of this prospective study was to investigate the
      feasibility of high-resolution magnetic resonance angiography (MRA) of the
      kidneys at 3.0 T using parallel data acquisition. MATERIAL AND METHODS: Contrast
      enhanced MRA of the renal arteries (RA) was performed in 12 volunteers and 12
      consecutive patients (mean age 47.1 +/- 16.3 years) on a 3.0 T MR scanner. For
      CEMRA, a high-resolution 3-dimensional GRE FLASH sequence was implemented. Images
      were assessed subjectively on a 0 to 5 scoring scale by 2 reviewers. Quantitative
      evaluation was done by measuring the contrast-to-noise ratio (CNR) and signal-to
      noise ratio (SNR). RESULTS: Diagnostic image quality was acquired in all
      individuals. In total, 62 RA were found, consisting of 48 main and 14 accessory
      RA. Overall visibility score for main RA was 4.82 +/- 0.38. RA were identified up
      to the third-order branches in 88%. In 3 of 12 patients, a hemodynamic relevant
      stenosis was found and proven by conventional angiogram. CONCLUSION: CEMRA at 3.0
      T is advantageous in terms of better SNR and T1 weighting; therefore, measurement
      time can be reduced and spatial resolution can be increased without corruption of
      signal yield. Consequently, high-field MRA may be preferred for the evaluation of
      renal vascular anatomy in potential kidney donors or for the detection of renal
      artery stenosis.

PMID- 16428985
TI  - Cardiac steady-state free precession CINE magnetic resonance imaging at 3.0
      tesla: impact of parallel imaging acceleration on volumetric accuracy and signal
      parameters.
AB  - OBJECTIVES: We sought to evaluate the impact of 3.0 T on accelerated CINE steady
      state free precession (SSFP) regarding signal parameters and its volumetric
      accuracy. MATERIAL AND METHODS: Ten individuals underwent cardiac CINE imaging at
      1.5 T and 3.0 T using standard single-slice CINE and multislice TSENSE
      accelerated CINE (5 slices/breath-hold) with 4-fold acceleration. Data were
      evaluated for left ventricular volumetric parameters (EDV, ESV, and EF) as well
      as for SNR and CNR. Phantom based data allowed for g-factor evaluation for
      estimation of noise levels for accelerated data sets. Volumetric results and
      signal parameters were compared with results of single-slice CINE SSFP at 1.5 T
      as standard of reference (SOR). RESULTS: Single-slice CINE at 3.0 T showed a
      approximately 90% increase in CNR compared with the SOR (P < 0.001). At 3.0 T,
      TSENSE CINE showed a less pronounced estimated loss in CNR (-58 +/- 6%) compared
      with single-slice CINE than at 1.5 T (-71 +/- 2%). 3.0 T TSENSE CINE showed a 21
      +/- 18% lower CNR than the nonaccelerated 1.5 T CINE (P < 0.05). EF results for
      all data sets did not show any significant error while for EDV some errors have
      been encountered. CONCLUSION: 3.0 T permits compensation for the high CNR loss,
      which accompanies the 4-fold TSENSE acceleration at 1.5 T and shows volumetric
      accuracy. The use of parallel imaging may help to alleviate SAR limitations at
      higher field strength.

PMID- 16428986
TI  - Phase-sensitive inversion recovery (PSIR) single-shot TrueFISP for assessment of
      myocardial infarction at 3 tesla.
AB  - PURPOSE: The aim of the current study was to show if contrast-to-noise ratio
      (CNR) could be improved without loss of diagnostic accuracy if a phase-sensitive
      inversion recovery (PSIR) single-shot TrueFISP sequence is used at 3.0 T instead
      of 1.5 T. MATERIAL AND METHODS: Ten patients with myocardial infarction were
      examined on a 1.5 T magnetic resonance (MR) system (Avanto, Siemens Medical
      Systems) and at a 3.0 T MR system. Imaging delayed contrast enhancement was
      started 10 minutes after application of contrast material. A phase-sensitive
      inversion recovery (PSIR) single-shot TrueFISP sequence was used at 1.5 and 3.0 T
      and compared with a segmented IR turboFLASH sequence at 1.5 T, which served as
      the reference method. Infarct volumes and CNR of infarction and normal myocardium
      were compared with the reference method. RESULTS: The PSIR Single-Shot TrueFISP
      technique allows for imaging nine slices during a single breathhold without
      adaptation of the inversion time. The mean value of CNR between infarction and
      normal myocardium was 5.9 at 1.5 T and 12.2 at 3.0 T (magnitude images). The CNR
      mean value of the reference method was 8.4. The CNR mean value at 3.0 T was
      significantly (P = 0.03) higher than the mean value of the reference method. The
      correlation coefficients of the infarct volumes, determined with the PSIR single
      shot TrueFISP technique at 1.5 T and at 3.0 T and compared with the reference
      method, were r = 0.96 (P = 0.001) and r = 0.99 (P = 0.0001). CONCLUSION: The use
      of PSIR single-shot TrueFISP at 3.0 T allows for accurate detection and
      assessment of myocardial infarction. CNR is significantly higher at 3.0 T
      compared with 1.5 T. The PSIR single-shot technique at 3.0 T provides a higher
      CNR than the segmented reference technique at 1.5 T.

PMID- 16428987
TI  - Comprehensive cardiac magnetic resonance imaging at 3.0 Tesla: feasibility and
      implications for clinical applications.
AB  - OBJECTIVE: The objective of this study was to examine the applicability of high
      magnetic field strengths for comprehensive functional and structural cardiac
      magnetic resonance imaging (MRI). SUBJECTS AND METHODS: Eighteen subjects
      underwent comprehensive cardiac MRI at 1.5 T and 3.0 T. The following imaging
      techniques were implemented: double and triple inversion prepared FSE for
      anatomic imaging, 4 different sets of echocardiographic-gated CINE strategies for
      functional and flow imaging, inversion prepared gradient echo for delayed
      enhancement imaging, T1-weighted segmented EPI for perfusion imaging and 2
      dimensional (2-D) spiral, and volumetric SSFP for coronary artery imaging.
      RESULTS: : Use of 3 Tesla as opposed to 1.5 Tesla provided substantial baseline
      signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) improvements for
      anatomic (T1-weighted double IR: DeltaSNR = 29%, DeltaCNR = 20%, T2-weighted
      double IR: DeltaSNR = 39%, DeltaCNR = 33%, triple IR: DeltaSNR = 74%, DeltaCNR =
      60%), functional (conventional CINE: DeltaSNR = 123%, DeltaCNR = 74%, accelerated
      CINE: DeltaSNR = 161%, DeltaCNR = 86%), myocardial tagging (DeltaSNRsystole =
      54%, DeltaCNRsystole = 176%), phase contrast flow measurements (DeltaSNR = 79%),
      viability (DeltaSNR = 48%, DeltaCNR = 40%), perfusion (DeltaSNR = 109%, DeltaCNR
      = 87%), and breathhold coronary imaging (2-D spiral: DeltaSNRRCA = 54%,
      DeltaCNRRCA = 69%, 3-D SSFP: DeltaSNRRCA = 60%, DeltaCNRRCA = 126%), but also
      revealed image quality issues, which were successfully tackled by adiabatic
      radiofrequency pulses and parallel imaging. CONCLUSIONS: Cardiac MRI at 3.0 T is
      feasible for the comprehensive assessment of cardiac morphology and function,
      although SAR limitations and susceptibility effects remain a concern. The need
      for speed together with the SNR benefit at 3.0 T will motivate further advances
      in routine cardiac MRI while providing an image-quality advantage over imaging at
      1.5 Tesla.

PMID- 16428988
TI  - Superparamagnetic iron oxide-enhanced liver magnetic resonance imaging:
      comparison of 1.5 T and 3.0 T imaging for detection of focal malignant liver
      lesions.
AB  - OBJECTIVES: We sought to compare the image quality, lesion conspicuity, and the
      diagnostic performance of 1.5 T and 3.0 T superparamagnetic iron oxide-enhanced
      liver magnetic resonance imaging (MRI) for detecting focal malignant hepatic
      lesions. MATERIALS AND METHODS: A total of 35 patients with pathologically proven
      liver malignancy underwent both 1.5 and 3.0 T SPIO-enhanced MRI. The diagnostic
      accuracy was evaluated using the alternative-free response receiver operating
      characteristic method. Image artifacts, quality, and the lesion conspicuity were
      analyzed. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of
      the lesion were calculated. RESULTS: No significant difference of area under ROC
      curve (Az value) was noted. The mean SNR and CNR of the lesions was higher in the
      3.0 T sets. There was no difference between the 1.5 T and the 3.0 T image sets
      for lesion conspicuity, but the image quality was better on 1.5 T. Motion and
      susceptibility artifacts were more frequent on 3.0 T. CONCLUSION: Diagnostic
      accuracies of the SPIO-enhanced MRI were equivalent on the 1.5 T and 3.0 T image
      sets. More prominent artifacts on 3.0 T superparamagnetic iron oxide-enhanced
      liver MRI counteracted advantage of higher SNR and CNR of 3.0 T.

PMID- 16428989
TI  - Magnetic resonance imaging of the pancreas at 3.0 tesla: qualitative and
      quantitative comparison with 1.5 tesla.
AB  - OBJECTIVES: We sought to perform a preliminary comparison of signal-to-noise
      ratio (SNR) and image quality for magnetic resonance imaging (MRI) of the
      pancreas at 1.5 and 3 T. MATERIALS AND METHODS: Two imaging cohorts were studied
      using a T2-weighted, single-shot fast spin-echo pulse sequence and a T1-weighted,
      fat-suppressed 3D gradient-echo pulse sequence. In the first cohort, 4 subjects
      were imaged using identical imaging parameters before and after contrast
      administration at 1.5 and 3.0 T. The SNR was quantified for the pancreas as well
      as for the liver, spleen, and muscle. In a second cohort of 12 subjects in whom
      the receiver bandwidth was adjusted for field strength, SNR measurements and
      qualitative rankings of image quality were performed. RESULTS: In the study
      cohort using identical imaging parameters at both magnetic field strengths, the
      mean (SD) ratios of SNR at 3.0 to 1.5 T of the single-shot fast spin-echo images
      for the pancreas, liver, spleen, and muscle were 1.63 (0.39), 1.82 (0.39), 1.45
      (0.18), 2.01 (0.16), respectively. For the precontrast fat-suppressed 3D gradient
      echo sequence, the corresponding ratios were 1.28 (0.29), 1.26 (0.30), 1.16
      (0.27), and 1.76 (0.45), respectively; for the arterial phase, the corresponding
      ratios were 2.02 (0.28), 1.60 (0.42), 1.47 (0.26), and 1.94 (0.32), respectively;
      and for the delayed postcontrast phase, the corresponding ratios were 1.63
      (0.51), 2.01 (0.25), 1.66 (0.06), and 2.31 (0.47), respectively. The SNR benefit
      of 3.0 T was significantly greater on contrast-enhanced as compared with
      noncontrast T1-weighted 3D gradient-echo images. In the second study cohort, SNR
      was superior at 3.0 T, although the use of a reduced readout bandwidth at 1.5 T
      substantially diminished the advantage of the higher field system. With
      qualitative comparison of images obtained at the 2 magnetic field strengths, the
      fat-suppressed 3D gradient-echo images obtained at 3.0 T were preferred, whereas
      the single shot fast spin-echo images obtained at 1.5 T were preferred because of
      better signal homogeneity. CONCLUSIONS: Our results in a small cohort of
      volunteers and patients demonstrate a marked improvement in SNR at 3.0 T compared
      with 1.5 T (by a factor of 2 in some cases) when identical imaging parameters
      were used. The SNR advantage at 3.0 T is diminished but persists when the
      receiver bandwidth is adjusted for magnetic field strength. The results suggest
      that 3.0 T may offer promise for improved body MRI, although further technical
      development to optimize SNR and improve signal homogeneity will be needed before
      its full potential can be achieved.

PMID- 16428990
TI  - Evaluation of intrarenal oxygenation at 3.0 T using 3-dimensional multiple
      gradient-recalled echo sequence.
AB  - OBJECTIVE: The objective of this study was to validate quantitation of R2* and
      DeltaR2* measurements obtained with a 3-dimensional (3-D) multiple gradient
      recalled echo (mGRE) sequence for evaluating intrarenal oxygenation in humans.
      MATERIALS AND METHODS: Validation was accomplished (1) by comparing R2* values
      with previously established 2-D techniques (n = 5, mean age = 33.6 years) and (2)
      by measuring change in DeltaR2* after furosemide (20 mg intravenously)
      administration (n = 5, mean age = 22 years). Additional pre- and postfurosemide
      scans were done at 1.5 T for comparison purposes. RESULTS: R2* measurements with
      the 3-D technique showed good agreement with the 2-D techniques. The baseline
      medullary R2* at 3.0 T was about twice the value found at 1.5 T. Furosemide
      induced change in R2* was observed within 5 minutes after administration.
      CONCLUSIONS: R2* measurements with 3-D mGRE were comparable with those reported
      using 2-D techniques. The 3-D implementation facilitates observation of temporal
      changes in the medullary oxygenation without compromising spatial coverage.

PMID- 16428991
TI  - Diffusion imaging of the prostate at 3.0 tesla.
AB  - OBJECTIVES: We sought to assess the efficacy of diffusion imaging in the
      differential diagnosis of prostatic carcinoma using a 3.0 T scanner and parallel
      imaging technology. MATERIALS AND METHODS: Diffusion-weighted images were
      acquired using a single shot echo-planar imaging sequence with b = 0 and 500
      seconds/mm. Apparent diffusion coefficient (ADCy) values were calculated in tumor
      and healthy-appearing peripheral zone for 62 patients. Diffusion tensor images
      were also acquired in 25 patients and mean diffusivity and fractional anisotropy
      determined. RESULTS: Significant differences were noted between prostatic
      carcinoma (1.33 +/- 0.32 x 10(-3) mm2/s) and peripheral zone (1.86 +/- 0.47 x 10(
      3) mm2/s) for ADCy. Significant differences between the 2 tissue types were also
      noted for mean diffusivity and fractional anisotropy. Utilizing a cut-off of 1.45
      x 10(-3) mm/s for mean diffusivity, a sensitivity of 84% and a specificity of 80%
      were obtained. CONCLUSIONS: Diffusion imaging of the prostate was implemented at
      high magnetic field strength. Reduced ADC and increased fractional anisotropy
      values were noted in prostatic carcinoma.

PMID- 16428992
TI  - Quantitative assessment of patellar cartilage volume and thickness at 3.0 tesla
      comparing a 3D-fast low angle shot versus a 3D-true fast imaging with steady
      state precession sequence for reproducibility.
AB  - OBJECTIVES: We sought to compare patellar cartilage volume and thickness
      measurement between 3D-FLASH and 3D-True fast imaging with steady-state
      precession (FISP) image data at 3.0 T. MATERIALS AND METHODS: One knee each of 6
      healthy adults was examined by axial magnetic resonance imaging (MRI) performed
      with a 3D-fast flow angle shot (FLASH) water-excitation sequence and a 3D
      TrueFISP water-excitation sequence (spatial resolution 0.31 x 0.31 x 1.5 mm3).
      Patellar cartilage volume and mean/maximum thickness were calculated.
      Intraindividual/average reproducibility and interindividual variability were
      determined from 3 consecutive data sets acquired for each volunteer and sequence.
      RESULTS: Patellar cartilage volume and thickness as well as reproducibility was
      slightly but not significantly lower for the 3D-TrueFISP data than for the 3D
      FLASH data (volume: 3.4-6.3 mL (3D-FLASH)/3.1-6.0 mL (3D-TrueFISP), average
      reproducibility 1.8% (3D-FLASH)/4.4% (3D-TrueFISP); mean thickness: 2.1-2.8 mm
      (3D-FLASH)/1.9-2.6 mm (3D-TrueFISP), average reproducibility 2.8% (3D-FLASH)/3.8%
      (3D-TrueFISP); maximum thickness: 4.7-6.6 mm (3D-FLASH)/4.5-6.2 mm (3D-TrueFISP),
      average reproducibility 2.6% (3D-FLASH)/4.1% (3D-TrueFISP)). Interindividual
      variability was comparable for both sequence techniques. CONCLUSION: At 3.0 T,
      the 3D-FLASH sequence showed tendency to be slightly superior to the 3D-TrueFISP
      sequence considering robust and valid assessment of quantitative cartilage
      parameters in young healthy adults, although there was found no significant
      statistical difference between both imaging techniques. However, in patients
      suffering from osteoarthritis (OA), the 3D-TrueFISP sequence might prove
      advantageous for monitoring of disease progression and evaluation of therapy
      success, particularly because the substantially higher signal to noise
      ratio/contrast to noise ratio values might allow for higher spatial resolution
      and hence for improvement of the accuracy of segmentation process especially at
      the articular surface.

PMID- 16428993
TI  - Three-dimensional T1 mapping for dGEMRIC at 3.0 T using the Look Locker method.
AB  - OBJECTIVE: The objective of this study was to implement a three-dimensional (3-D)
      T1 mapping sequence (3DLL) at 3.0 T for dGEMRIC based on the Look Locker scheme.
      MATERIALS AND METHODS: Because all current reports on dGEMRIC are at 1.5 T and
      mostly using 2-D IR fast spin echo (FSE), data were acquired at 1.5 T and 3.0 T
      with both 3DLL and 2-D IR-FSE sequence. Phantoms with different concentrations of
      Gd(DTPA) were used and seven subjects (three asymptomatic, four symptomatic) were
      scanned using the dGEMRIC technique. RESULTS: The T1 measurements obtained on the
      phantom with 3DLL show very good agreement with those acquired with 2-D IR-FSE.
      Using a two-tailed paired t test, the T1 (Gd) measurements in two sections
      obtained in all subjects with both sequences were found to be statistically
      indistinguishable at either field strength (P = 0.07 at 1.5 T and P = 0.07 at 3.0
      T). CONCLUSIONS: The preliminary data presented here suggest that the 3DLL
      sequence provides accurate T1 values with sufficient in-plane resolution and
      allows full joint coverage in less than 10 minutes.

PMID- 16428996
TI  - Peripheral intravenous catheter dwell times: a comparison of 3 securement methods
      for implementation of a 96-hour scheduled change protocol.
AB  - A prospective, sequential clinical trial was undertaken to determine whether any
      of 3 methods of peripheral IV catheter (PIV) securement could extend the average
      survival time of such catheters sufficiently to allow the implementation of a 96
      hour PIV change-protocol. Nonsterile tape, StatLock, and Hub-Guard were
      evaluated. The use of nonsterile tape securement resulted in an 8% PIV survival
      rate, HubGuard produced a 9% PIV survival rate, and Statlock produced a 52% PIV
      survival rate (P<.001). Although this study was not a randomized, controlled
      trial, it strongly suggests that a mechanical catheter securement device, as
      opposed to tape or die-cut tape, can render practicable the implementation of the
      96-hour PIV change protocol that was sanctioned by the Centers for Disease
      Control and Prevention.

PMID- 16428997
TI  - An overview of intravenous-related medication administration errors as reported
      to MEDMARX, a national medication error-reporting program.
AB  - Medication errors can be harmful, especially if they involve the intravenous (IV)
      route of administration. A mixed-methodology study using a 5-year review of
      73,769 IV-related medication errors from a national medication error reporting
      program indicates that between 3% and 5% of these errors were harmful. The
      leading type of error was omission, and the leading cause of error involved
      clinician performance deficit. Using content analysis, three themes-product
      shortage, calculation errors, and tubing interconnectivity-emerge and appear to
      predispose patients to harm. Nurses often participate in IV therapy, and these
      findings have implications for practice and patient safety. Voluntary medication
      error-reporting programs afford an opportunity to improve patient care and to
      further understanding about the nature of IV-related medication errors.

PMID- 16428998
TI  - Peripherally inserted central catheters in children: a survey of practice
      patterns.
AB  - There is little published information describing standards of practice in the
      placement, use, and maintenance of peripherally inserted central catheter (PICC)
      devices in children. A Web-based survey tool was designed to query these issues,
      and 72 intravenous therapy nurses from 72 hospitals provided complete responses
      to the survey. The respondents were predominantly (81%) from healthcare
      organizations inserting 40 or fewer PICC devices per month. These hospitals were
      equally divided in using 0.9% sodium chloride (USP) (saline) or heparinized
      saline flush to maintain patency, whereas 76% used catheters for blood sampling.
      Flushing and blood sampling practices were not related to catheter occlusion
      rates. From their survey, the authors conclude that the standards of practice for
      3-Fr PICC devices, the most commonly used for children, are quite variable and in
      need of standardization for this specific population.

PMID- 16428999
TI  - Why are we stuck on tape and suture? A review of catheter securement devices.
AB  - This review focuses on available prospective data comparing standard methods of
      catheter securement with a securement device. The data demonstrate that the
      device, specifically engineered for catheter securement, significantly reduces
      overall catheter-associated complications. This appears to be the result of
      improved securement and reduced catheter motion. These studies make the authors
      question their current practice of securing catheters with tape and suture when
      better alternatives are available.

PMID- 16429000
TI  - Anaphylaxis.
AB  - Anaphylaxis is a severe systemic allergic reaction that can involve multiple
      systems of the body. Anaphylaxis often is unpredictable, can have a rapid onset,
      and, if serious enough, can have life-threatening consequences. If an
      anaphylactic reaction is the result of an antigen antibody response, it is
      considered anaphylaxis. If the reaction is caused by a nonantibody trigger, it is
      considered anaphylactoid. Clinically, however, both responses appear the same and
      require the same management and treatment. With the development of new protein
      drugs and their use as therapeutic agents, the risk of anaphylaxis will most
      likely increase. For this reason, the infusion nurse specialist needs to have the
      knowledge and skills necessary to recognize and respond appropriately when
      anaphylaxis occurs. This article discusses the history, definition, incidence,
      risk factors, etiology, pathophysiology, and clinical findings of anaphylaxis.
      Appropriate prevention, management, and treatment also are discussed, with
      special attention given to medication-related anaphylaxis.

PMID- 16429002
TI  - Infusion Nursing Standards of Practice.

PMID- 16429082
TI  - Stuttering improved with risperidone.

PMID- 16429083
TI  - Family cognitive behavioral therapy for children and adolescents with clinical
      anxiety disorders.
AB  - OBJECTIVE: A family cognitive-behavioral therapy for children and adolescents
      ages 8 to 18 years with clinical anxiety disorders was developed and evaluated.
      METHOD: Seventeen families were measured before and after wait list, after
      treatment, and at 3-month and 1-year follow-up. RESULTS: No children changed
      their diagnostic status during wait list, whereas of the treated children, 41%
      were free of their primary anxiety disorder posttest, 57% at 3-month follow-up,
      and 71% at 1-year follow-up. Effect sizes of improvement were large for
      children's fears, dysfunctional beliefs, and interpretations of ambiguous
      situations and medium for children's internalizing and externalizing symptoms.
      Interestingly, fathers but not mothers reported less anxiety themselves after
      treatment. Large improvements were observed on parents' dysfunctional beliefs
      about their child's anxiety and their role as a parent. Finally, some
      improvements occurred in family and rearing variables. CONCLUSIONS: Family
      cognitive-behavioral therapy seems effective for clinically anxious children and
      their families.

PMID- 16429084
TI  - Combination lithium and divalproex sodium in pediatric bipolar symptom re
      stabilization.
AB  - OBJECTIVE: It has been reported that bipolar disorder may become less responsive
      to previously effective treatment with each symptomatic relapse. The primary goal
      of this study was to assess the rate of re-stabilization after the resumption of
      lithium (Li) plus divalproex (DVPX) following relapse on either agent as
      monotherapy. METHOD: This is a prospective, 8-week, open-label outpatient Li/DVPX
      combination therapy trial. Patients ages 5 to 17 years with bipolar disorder type
      I or II, who had achieved symptom remission with Li/DVPX combination therapy and
      subsequently relapsed during treatment with Li or DVPX monotherapy were enrolled
      between January 1999 and January 2003. RESULTS: Thirty-eight patients with a mean
      age of 10.5 years entered the study. Thirty-four (89.5%) patients responded to
      treatment with Li/DVPX mood stabilizer therapy alone, but four patients required
      adjunctive antipsychotic treatment to address residual symptomatology. Overall,
      reinitiation of Li/DVPX combination therapy was well tolerated with no subjects
      discontinuing because of a medication-related adverse event. CONCLUSIONS: It
      appears that most youths with bipolar disorder who stabilize on combination
      Li/DVPX therapy and subsequently relapse during monotherapy can safely and
      effectively be re-stabilized with the reinitiation of Li/DVPX combination
      treatment.

PMID- 16429085
TI  - Do children and adolescents with ADHD respond differently to atomoxetine?
AB  - OBJECTIVE: Controversy exists over changes in tolerability and response to
      medications across the life span. Here the authors report data contrasting the
      efficacy and tolerability of atomoxetine between children and adolescents with
      attention-deficit/hyperactivity disorder (ADHD). METHOD: Data were analyzed for
      children ages 6-11 (510 atomoxetine, 341 placebo) and adolescents ages 12-17 (107
      atomoxetine, 69 placebo) with DSM-IV-defined ADHD enrolled in similarly designed,
      double-blind, placebo-controlled trials. Efficacy measures included response
      rates, times to response, and mean changes from baseline to endpoint in the ADHD
      Rating Scale, Conners' Parent Rating Scale, and Clinical Global Impressions.
      RESULTS: Adolescents had lower baseline ADHD scores compared with children. There
      were no statistically significant differences in the overall effects on ADHD
      symptoms, response rates, or time to response between age groups. Children, but
      not adolescents, had higher rates of somnolence and headache relative to placebo.
      No other clinically meaningful treatment differences were seen in adverse event
      rates, vital signs, weight, height, laboratory values, or ECG between children
      and adolescents. CONCLUSIONS: Acute atomoxetine treatment appears to be equally
      effective and tolerated in children and adolescents. These findings suggest that
      pharmacological differences in tolerability or ADHD symptom response are
      negligible between children and adolescents.

PMID- 16429086
TI  - Depression experience journal: a computer-based intervention for families facing
      childhood depression.
AB  - OBJECTIVE: This study tested the feasibility and safety of a computer-based
      application for families facing childhood depression. The Depression Experience
      Journal (EJ) is a psychoeducational intervention based on a narrative model
      involving the sharing of personal stories about childhood depression. METHOD:
      Semistructured interviews assessed Depression EJ feasibility and safety. Thirty
      eight primary caretakers of children with depression (one caretaker per patient)
      used the EJ during a psychiatric hospitalization. Assessment of feasibility and
      safety was measured before EJ use and 2 to 4 weeks afterward. RESULTS: Results
      revealed that the EJ was safe and useful for decreasing social isolation,
      increasing hope, increasing understanding of familial feelings about childhood
      depression, and fostering positive reactions in caretakers. CONCLUSIONS: Computer
      based interventions hold significant promise in providing a new manner of
      psychosocial support to families facing child and adolescent psychiatric
      illnesses.

PMID- 16429087
TI  - An electronic diary study of contextual triggers and ADHD: get ready, get set,
      get mad.
AB  - OBJECTIVE: This study was designed to examine context effects or provocation
      ecologies in the daily lives of children with ADHD. METHOD: Across 7 days,
      mothers and children (27 children with attention-deficit/hyperactivity disorder
      [ADHD] taking stimulant medication; 25 children without ADHD; ages 7-12 years)
      provided electronic diary reports every 30 +/- 5 minutes during non-school hours.
      Child and maternal perceptions of behaviors, moods, and interaction quality
      during preparatory and transitional ("getting ready") activities were compared
      with those during other activities. RESULTS: Maternal reports revealed that child
      symptomatic behaviors and negative moods, maternal negative moods, and parent
      child disagreement were elevated in the ADHD but not in the comparison group
      while getting ready versus other activities. Children's self-ratings also
      revealed situational effects, indicating that school-age children with ADHD can
      give meaningful self-reports using carefully structured electronic diaries.
      CONCLUSIONS: Even when children with ADHD are receiving stimulant
      pharmacotherapy, the preparatory tasks of daily living are especially challenging
      and linked disproportionately to child behavior problems, parent negative affect,
      and contentious interactions. Treatment targeted on these transitional hurdles
      may improve child behavior patterns and enhance parent-child relationships and
      family harmony.

PMID- 16429088
TI  - A risk-taking "set" in a novel task among adolescents with serious conduct and
      substance problems.
AB  - OBJECTIVE: Adolescent patients' conduct disorder and substance use disorder
      symptoms are "risky behaviors" with unpredictable rewards and punishments. The
      authors asked whether such youths also take excessive risks in new situations
      without prior learning, peer pressure, or intoxication. METHOD: Subjects were 20
      adolescent patients in a program treating conduct disorder and substance use
      disorder and 20 controls. All were substance free > or =7 days; underwent
      substance-related, psychological, and social assessments; and performed the
      Balloon Analogue Risk Task: mouse presses inflated a computerized "balloon"
      image, each press earning 1 cent. The 30 balloons "popped" at unpredictable
      sizes; earnings from popped balloons were lost. A "Collect" response saved
      current earnings and advanced to the next balloon. RESULTS: Mean number of
      inflating presses: patients, 1021 and controls, 705 (p = .001); group differences
      were stable from the task's beginning. Mean inflating presses before a "collect"
      response: patients, 38.6 and controls, 24.0 (p = .0005). Mean balloons popped:
      patients, 9.8 and controls, 6.3 (p = .001). Patients (versus controls) reported
      more aggressiveness and substance use and perceived less risk from substances.
      Patients' responses were significantly slower than those of controls.
      CONCLUSIONS: From the beginning of this novel task, conduct disorder and
      substance use disorder patients (compared with controls) took more risks,
      indicating an initial risk-taking propensity, although patients' slower responses
      argued against "impulsive, thoughtless" behavior.

PMID- 16429089
TI  - Preadolescent conduct problems in girls and boys.
AB  - OBJECTIVE: To examine sex differences in correlates of disruptive behavior
      disorders (DBDs) in preadolescent children using indicators of a wide range of
      well-established risk factors for DBDs and outcomes 3 years after initial
      assessment. METHOD: Analyses were based on data for 5- to 10-year-olds (n =
      5,913) from the British Child and Adolescent Mental Health Survey 1999, and a 3
      year follow-up of selected subsamples (n = 1,440) at ages 8 through 13 years. DSM
      IV diagnoses were assigned using the Developmental and Well-Being Assessment at
      both contacts. RESULTS: Boys and girls were equally exposed to most social and
      family risks for DBDs, with little evidence of differential sensitivity to these
      risks. Boys were exposed more to neurodevelopmental difficulties, attention
      deficit/hyperactivity disorder, and peer problems and had lower rates of
      prosocial behaviors; together, these factors and physical punishment could
      account for 54% of the observed sex differences in DBDs. At follow-up, outcomes
      for girls and boys with DBDs were very similar. For children with subthreshold
      conduct problems at initial assessment, boys were more likely to go on to exhibit
      DBDs than were girls (25% versus 7%). CONCLUSIONS: Sex differences in the levels
      of a variety of child characteristics and interpersonal factors are likely to be
      important in understanding sex differences in risk for DBDs in preadolescent
      samples.

PMID- 16429090
TI  - Young adult outcome of hyperactive children: adaptive functioning in major life
      activities.
AB  - OBJECTIVE: The authors report the adaptive functioning of hyperactive and control
      children in southeastern Wisconsin (Milwaukee) followed to young adulthood.
      METHOD: Interviews with participants concerning major life activities were
      collected between 1992 and 1996 and used along with employer ratings and high
      school records at the young adult follow-up (mean = 20 years, range 19-25) for
      this large sample of hyperactive (H; n = 149) and community control (CC; n = 72)
      children initially seen in 1978-1980 and studied for at least 13 years. Age,
      duration of follow-up, and IQ were statistically controlled as needed. RESULTS:
      The H group had significantly lower educational performance and attainment, with
      32% failing to complete high school. H group members had been fired from more
      jobs and manifested greater employer-rated attention-deficit/hyperactivity
      disorder and oppositional defiant disorder symptoms and lower job performance
      than the CC group. Socially, the H group had fewer close friends, more trouble
      keeping friends, and more social problems as rated by parents. Far more H than CC
      group members had become parents (38% versus 4%) and had been treated for
      sexually transmitted disease (16% versus 4%). Severity of lifetime conduct
      disorder was predictive of several of the most salient outcomes (failure to
      graduate, earlier sexual intercourse, early parenthood) whereas attention
      deficit/hyperactivity disorder and oppositional defiant disorder at work were
      predictive of job performance and risk of being fired. CONCLUSIONS: These
      findings corroborate prior research and go further in identifying sexual activity
      and early parenthood as additional problematic domains of adaptive functioning at
      adulthood.

PMID- 16429091
TI  - An observational analysis of behavior in depressed preschoolers: further
      validation of early-onset depression.
AB  - OBJECTIVE: To investigate whether higher levels of negative and lower levels of
      positive behaviors could be observed in a sample of depressed preschoolers.
      Support for the validity of preschool depression is now available; however,
      objective evidence of negative behaviors among depressed preschoolers is needed.
      METHOD: A structured observational parent-child interaction task was conducted.
      The behaviors of 152 preschoolers (ages 3.0-5.6) in three study groups
      (depressed, disruptive, and healthy) were examined with further analyses of
      depressed subgroups based on severity and comorbidity. RESULTS: Anhedonically
      depressed preschoolers emerged as demonstrating less enthusiasm, more avoidance,
      more noncompliance, and having a more negative overall experience than healthy
      controls. This more severe and proposed melancholic anhedonic subgroup also
      displayed less enthusiasm than nonanhedonically depressed preschoolers.
      Furthermore, the "pure" anhedonic depressed preschoolers without disruptive
      comorbidity emerged as the only depressed subgroup that was significantly
      distinguishable from healthy preschoolers. CONCLUSIONS: Findings provide the
      first objective evidence of more negative and fewer positive behaviors among
      depressed preschoolers. Notably, the finding that anhedonically depressed
      preschoolers demonstrated significantly less enthusiasm than those with
      nonanhedonic depression provides the first objective evidence of the
      manifestation of anhedonia, a key sign of preschool depression. The implications
      of the finding that the "pure" anhedonic depressed subgroup without disruptive
      comorbidity was most distinguishable from comparison groups are explored.

PMID- 16429092
TI  - Preschoolers' depression severity and behaviors during dyadic interactions: the
      mediating role of parental support.
AB  - OBJECTIVE: To investigate the relationship between preschool depression severity,
      observed behavior, and parental emotional support in a population of 3.0- to 5.6
      year-olds and their mothers. METHOD: One hundred fifty preschoolers who underwent
      a comprehensive mental health assessment during which DSM-IV diagnoses were
      derived were included in this analysis. Child and parent behaviors during
      challenging structured dyadic tasks were systematically coded. Dyads with
      preschoolers in three diagnostic groups of interest were explored: depression,
      disruptive, and healthy. Depression severity sum scores were derived for children
      in all of the groups. RESULTS: Depression severity accounted for a significant (p
      < .05) portion of the variance in preschoolers' persistence, compliance, and
      enthusiasm during dyadic tasks after controlling for the effects of age and
      gender. Depression severity was also significantly associated with parental
      emotional support, which was itself associated with all three preschool
      behaviors. When the effect of parental support was controlled for statistically,
      however, preschoolers' depression severity was no longer significantly associated
      with observed persistence or compliance, whereas the relationship between
      depression severity and enthusiasm remained significant. CONCLUSIONS: Maternal
      emotional support mediated the relationship between preschoolers' depression
      severity and their persistence and compliance but not the relationship between
      depression severity and enthusiasm. Findings have important clinical implications
      because they suggest that both external relational and internal child factors may
      be operating in preschool depression.

PMID- 16429093
TI  - Predictors and correlates of high levels of depression and anxiety symptoms among
      children at age 10.
AB  - OBJECTIVE: To identify factors that predict or are correlated with symptoms of
      depression and anxiety in 10-year-olds. METHOD: Women and their offspring were
      followed from the fourth prenatal month through 10 years. There were 636 mother
      child pairs at 10 years, a follow-up rate of 83% of the birth cohort. Cognitive,
      psychological, sociodemographic, and environmental factors were measured at each
      phase. High depression and anxiety were defined as having a number of symptoms >1
      SD above the mean for each measure. These measures were combined to represent
      high depression and/or anxiety (D/A) at 10 years of age. RESULTS: Predictors from
      the prenatal period of D/A at 10 years were more maternal depression symptoms,
      African American race, less social support, greater household density, and
      prenatal marijuana exposure. From 18 months through 6 years, lower child IQ,
      child injuries at age 3, and attention problems predicted symptoms of D/A at age
      10. Across all study phases, lower child IQ, household density during pregnancy,
      attention problems, early childhood injuries, and prenatal marijuana exposure
      predicted D/A. Maternal psychological and sociodemographic factors were not
      significant in the final model. CONCLUSIONS: Factors from gestation and early
      childhood predict high symptom levels of depression and anxiety at age 10. When
      gestational exposure, early environmental factors, and child characteristics were
      considered, maternal depression and socioeconomic status were not significantly
      associated with early onset D/A. Marijuana exposure during gestation marginally
      predicted depression/anxiety at age 10.

PMID- 16429094
TI  - High prevalence of self-reported depressive mood during the winter season among
      Swedish senior high school students.
AB  - OBJECTIVE: There are few studies regarding the prevalence of seasonal variation
      in mood among children and adolescents. The main objective of this study was to
      estimate the prevalence of self-reported depressive mood during the winter season
      among Swedish adolescents and to investigate gender differences. Another aim was
      to analyze the factor structure and internal consistency of the Kiddie SPAQ (K
      SPAQ), a pediatric version of the Seasonal Pattern Questionnaire (SPAQ). METHOD:
      All students 17 to 18 years old, registered in the second year of senior high
      school in Falun, a district in central Sweden, were screened with the K-SPAQ in
      January 2003 (response rate 87.3%, n = 756). RESULTS: The prevalence of self
      reported depressive mood during the winter season was estimated at 20.1% (n =
      151/751) and was higher among girls (25.5%) than boys (13.8%). Approximately 8%
      reported more severe depressive symptoms. Depressive mood during the summer was
      rare (0.1%, n = 1/751). Factor analysis of the General Seasonal Score items in
      the K-SPAQ revealed a two-factor structure. A Cronbach's alpha of 0.87
      demonstrated a good internal consistency. CONCLUSIONS: Depressive symptoms during
      autumn and winter were common among Swedish senior high school students,
      especially among girls. This is probably an underdiagnosed condition among
      adolescents that ought to receive more attention from the health and school
      authorities.

PMID- 16429095
TI  - Changes in children's behavior and costs for service use associated with parents'
      response to treatment for dysthymia.
AB  - OBJECTIVE: This study examined differences in children's behavior and
      expenditures for health and social services used when their parents with
      dysthymia did or did not respond to antidepressant therapy. METHOD: Children ages
      4 to 16 years of consenting parents enrolled in a treatment trial for dysthymia
      who did and did not respond to treatment were compared at baseline and 24 months.
      The responder was a parent with at least a 40% reduction in his or her baseline
      depressive symptoms using the Montgomery Asberg Depression Rating Scale.
      Children's behavior was measured using the Child Behavior Checklist, and
      expenditures for health and social services use was measured in Canadian dollars
      using the Health and Social Service Utilization Questionnaire. RESULTS: Children
      of parents with dysthymia who responded to treatment had significantly greater
      reductions in emotional symptoms at 2-year follow-up than children of
      nonresponders, along with an economically important (not statistically
      significant) reduction in expenditures for health and social services use.
      CONCLUSIONS: Reductions in parental symptoms of dysthymia may be associated with
      reductions in childhood behavioral problems and in expenditures for the child's
      use of services.

PMID- 16429096
TI  - Monitoring and managing outcomes in residential treatment: practice-based
      evidence in search of evidence-based practice.

PMID- 16429098
TI  - Use of aromatase inhibitors in children with short stature.
AB  - Estrogen has been shown to have an important role in skeletal maturation in both
      males and females. The use of aromatase inhibitors may provide a means to delay
      skeletal maturation and increase final height in children with short stature.
      These medications have been used primarily in women with breast carcinoma and
      also in children with autonomous estrogen production, such as patients with
      McCune-Albright Syndrome. Several studies have evaluated the safety and metabolic
      effects in adults. A few studies in children have evaluated the efficacy and
      safety of these medications. These studies demonstrate a beneficial effect on
      bone age advancement and predicted adult height. Other studies have evaluated the
      effects on bone mineral density, lipid metabolism and adrenal function in
      children. This review summarizes the studies in the pediatric population and some
      of the metabolic effects in adults.

PMID- 16429099
TI  - Ghrelin: a new hormone with endocrine and non-endocrine activities.
AB  - Ghrelin, the new and recently discovered hormone, is a 28 amino-acid acylated
      peptide predominantly produced by the stomach, characterized by a strong GH
      releasing activity mediated by the hypothalamic-pituitary GH Secretagogues (GHSs)
      receptors. Ghrelin and GHSs, acting on central and peripheral receptors, exert
      other actions such as: stimulation of ACTH and prolactin secretion; influence
      insulin secretion and glucose metabolism; have an orexigenic effect and
      modulatory activity on the neuroendocrine and metabolic response to starvation;
      influencing exocrine gastro-entero-pancreatic functions; influencing
      cardiovascular activities and modulation of cell proliferation and apoptosis.
      With the discovery of ghrelin and the characterization of these GH-independent
      biological activities, we have to pay more attention to these molecules as
      candidate drugs for the treatment of pathophysiological conditions including
      those unrelated to GH secretion disorders.

PMID- 16429100
TI  - Masculinizing genitoplasty in male pseudohermaphroditism.
AB  - In the last decades there is a shifting paradigm in the understanding of intersex
      conditions with regards to the gender assignment and the choice of the surgical
      technique for genitoplasty. The cosmetic and functional results of masculinizing
      genitoplasty are rarely assessed in the literature. We reviewed the medical
      literature regarding primary diagnosis, gender assignment, preoperative
      evaluation, goals of surgical correction, timing of surgery and surgical
      technique. We critically reviewed our technique of masculinizing genitoplasty in
      55 patients. In conclusion, we believe that this masculinizing genitoplasty is a
      feasible procedure in most of the patients with ambiguous genitalia raised as
      males with satisfactory functional and cosmetic results.

PMID- 16429101
TI  - Autoimmune and non-autoimmune hyperthyroidism in pediatric patients: a review and
      personal commentary on management.
AB  - Here we review the etiology, diagnosis, differential diagnosis, and clinical
      presentation of hyperthyroidism in neonates/infants, children, and adolescents
      and the standard and adjunct modalities used for its treatment. The most common
      cause of hyperthyroidism in pediatric patients is Graves' disease. The main
      options for its management include antithyroid drugs, surgery, and radioiodine
      therapy. Despite collective experience covering more than 4 decades in the
      management of hyperthyroidism in children, controversy still abounds regarding
      the choice of treatments. None of the current treatment options is ideal. Each
      has risks and selection should be tailored to individual patients, especially in
      view of the absence of large, prospective, randomized outcome studies. Finally,
      we discuss the diagnosis and management of less common causes of pediatric
      hyperthyroidism, including non-autoimmune causes in neonates, autonomously
      functioning thyroid adenomas, destructive thyroiditis, excessive or inappropriate
      thyroid-stimulating hormone production, excessive ingestion of thyroid hormone
      and exposure to large, stable iodine loads.

PMID- 16429102
TI  - Progeria: a new kind of Laminopathy-- report of the First European Symposium on
      Progeria and creation of EURO-Progeria, a European Consortium on Progeria and
      related disorders.
AB  - Progeria is a rare, genetically determined condition characterized by accelerated
      aging in children. Its name is derived from Greek (Geron) and means "prematurely
      old". The classic type is the Hutchinson-Gilford Progeria Syndrome (HGPS), which
      was first described in England in 1886 by Dr. Jonathan Hutchinson (1) and again
      in 1904 by Dr. Hastings Gilford (2). Since then and up to now, very little
      advancement toward the understanding of this devastating disorder has been
      accomplished. In early 2003 a French group succeeded in identifying point
      mutations in the LMNA gene, encoding A-type lamins, as the main cause of this
      disorder. These results were concomitantly confirmed by an American group, who
      identified mutations in LMNA, working on a large cohort of patients (3,4). HGPS
      is thus the most severe disorder added to the expanding list of "laminopathies",
      diseases caused by mutations in the LMNA gene encoding A-type lamins. To date, up
      to ten disorders are associated with mutations in LMNA. These disorders are
      diverse, both in their symptomatology and pattern of inheritance (see below and
      table 1). Due to the extremely low prevalence of progeria and the putative
      functional links between progeria and other premature aging disorders, setting-up
      a network about these disorders has become an absolute necessity. A reunion of
      families with a child affected with progeria, gathered within the European
      Progeria Family Circle, was held from September 25th to 29th 2003 in Magdeburg,
      Germany. In parallel to this event, a scientific symposium centered on clinical
      and molecular update of HGPS and related syndromes was organised. Several
      international experts, including clinical and molecular geneticists, cell
      biologists involved in the field of laminopathies, as well as paediatricians and
      other physicians with clinical experience in diagnosis, treatment and research on
      progeria and progeria-like syndromes presented their experience as well as their
      research projects and yet unpublished results. The main discussed topics as well
      as the developing research fields on progeria and related premature ageing
      disorders will be presented here.

PMID- 16429104
TI  - Prenatal treatment of intrauterine growth restriction: lessons from the sheep
      model.
AB  - Intrauterine growth restriction (IUGR) has both immediate and long-term
      consequences for the affected fetus, resulting in increased perinatal morbidity
      and mortality, growth failure, intellectual deficits and an increased risk of
      adult diseases including cardiovascular disease, diabetes and stroke. Although
      the diagnosis is now easily made, as yet there are no treatments available for
      established IUGR. Postnatal interventions to increase growth have not been
      demonstrated to reduce long-term consequences. It is theoretically possible that
      intrauterine interventions might reduce both the immediate perinatal risks and
      also those of adverse long term outcomes. The sheep has long been used to study
      fetal physiology, including IUGR. This paper will discuss the various routes of
      administration (mother, fetus and amniotic fluid) of various interventions
      (nutritional, hormonal or both) that have been tested experimentally. Several
      interventions have been demonstrated to prevent IUGR and some show promise in
      reversal of established IUGR, but none yet provide a definitive treatment. It may
      be that a much greater understanding of the hormonal and metabolic regulation of
      fetal growth is necessary before a successful treatment will be found.

PMID- 16429105
TI  - Neonatal Diabetes Mellitus -- genetic aspects 2004.
AB  - Transient (TNDM) and Permanent (PNDM) Neonatal Diabetes Mellitus are rare
      conditions occurring in 1:400,000-500,000 live births. In TNDM growth retarded
      infants develop diabetes in the first few weeks of life only to go into remission
      in a few months with possible relapse to a permanent diabetes state usually
      around adolescence or as adults. We believe that pancreatic dysfunction in this
      condition is maintained throughout life with relapse initiated at times of
      metabolic stress such as puberty or pregnancy. In PNDM, insulin secretory failure
      occurs in the late fetal or early post-natal period. A number of conditions are
      associated with PNDM, some of which have been elucidated at the molecular levels
      Among those, the very recently elucidated mutations in KCNJ11 gene, encoding the
      Kir6.2 subunit of the pancreatic KATP channel involved in regulation of insulin
      secretion accounts for one third to a half of the PNDM cases.

PMID- 16429106
TI  - Adult female outcomes of feminising surgery for ambiguous genitalia.
AB  - For the last half a century, feminising genital surgery has been routine practice
      for children with ambiguous genitalia assigned to a female sex of rearing. Due to
      various factors including the stigma and secrecy associated with intersex and the
      practical difficulties of paediatricians following-up adult patients, there has
      been little available outcome data on this policy. Recently however adult peer
      support groups have expressed dissatisfaction with the results of surgery. In
      addition there is increasing data to confirm a high rate of repeat vaginoplasty
      as well as a detrimental effect on adult sexual function. The lack of outcome
      data supporting this policy of genital surgery for all means it is time to
      radically evaluate our clinical practice. The option of psychological and peer
      support as an alternative to routine genital surgery must become a realistic
      proposition.

PMID- 16429107
TI  - Potassium handling in health and disease: lessons from inherited tubulopathies.
AB  - The tight regulation of plasma potassium levels, a mostly intracellular cation,
      is essential given the severe consequences of hyper- and hypokalemia. Basic renal
      physiology studies in the past have identified the complex pathway of potassium
      reabsorption in the proximal tubule followed by the fine-tuning of its secretion
      or reabsorption at the distal tubule, including the thick ascending limb of
      Henle's loop, the distal convoluted tubule and the cortical collecting duct.
      Genetic studies in recent years have clarified the role of specific tubular
      channels and transporters in the pathogenesis of unique hyperand hypokalemic
      tubulopathies, some of them non-hypertensive (pseudohypoaldosteronism, Bartter
      and Gitelman syndromes) and others hypertensive by definition (including Liddle
      and Gordon syndromes). This article reviews the genetic and clinical spectrum of
      hypokalemic and hyperkalemic tubulopathies. ABBREVIATIONS: K: potassium, Na:
      sodium; Cl: chloride; BS: Bartter syndrome; PHA: pseudohypoaldosteronism; NKCC2:
      bumetanide-sensitive Na-K-2Cl- co-transporter; ROMK: inwardly rectifying K
      channel; ClC-Kb: basolateral Cl channel; TAL: thick ascending limb of Henle's
      loop; TSC: thiazide-sensitive NaCl co-transporter; CCD: cortical collecting duct;
      ENaC: epithelial Na channel.

PMID- 16429108
TI  - Metabolic abnormalities in growth hormone deficiency.
AB  - Growth hormone has been implicated in the regulation of cardiovascular function
      and growth hormone deficiency (GHD) has been postulated to be one of the main
      factors responsible for the increased morbidity and mortality from cardiovascular
      disease in both young and older patients with childhood- and adulthood-onset GHD.
      Growth hormone also influences bone turnover and mineral deposition. Subjects
      with growth hormone deficiency have been shown to have an increased
      cardiovascular risk as manifested by elevated fasting and postprandial lipids and
      by increased body fat. In addition, premature atherosclerosis, decreased
      fibrinolytic activity, increased peripheral insulin resistance, abnormal cardiac
      structure and impaired cardiac performance have also been reported in this group
      of patients. Short and long term growth hormone treatment has been shown to exert
      beneficial effects on several of these parameters. While most of these
      abnormalities have been reported in adult GHD patients, metabolic changes in GHD
      children and adolescents have only recently begun to be investigated in more
      detail.

PMID- 16429109
TI  - New supplements to infant formulas.
AB  - Foods, which, in addition to their nutritional attributes, contain also elements
      that are considered to be health-promoting, have been termed "functional foods".
      In this regard, human milk has gained recognition as being the ultimate
      functional food for infants - by its biological compatibility, nutritional value
      and the undisputed added value of its health promoting qualities. Intensive
      research activity has recently evolved in a quest to identify and define the
      components of human milk that might confer disease-preventing and health
      enhancing properties and to determine the instances and clinical conditions in
      which these factors become particularly important. The outcome of such research
      would also provide a rationale for advocating the supplementation of commercial
      infant formulas with such substances. In effect, the body of data accumulated
      from scientific and clinical studies on nucleotides, probiotics, prebiotics and
      long-chain polyunsaturated fatty acids in human milk and as additives to infant
      formula, has become regarded as convincing enough by the infant formula industry
      so as to launch into the market formulas supplemented with one or more of these
      factors - in an effort to emulate human milk and its beneficial effects. The
      following review is intended for the reader to obtain a general idea of the new
      supplements that have been introduced to infant formulas. We summarize the
      pertinent experimental and clinical observations concerning each of the
      supplements, pointing out their potential specific benefits, their possible
      disadvantages and the issues that still remain unresolved.

PMID- 16429111
TI  - Confusion around the definition of small for gestational age (SGA).

PMID- 16429112
TI  - Growth hormone and SOCS2 regulation of neuronal differentiation: possible role in
      mental function.
AB  - Although many overgrowth and growth deficient patients have apparently normal
      neuropsychological and cognitive functions, there is evidence to suggest that in
      some instances these functions are somewhat impaired. Altered growth hormone (GH)
      signaling is primarily responsible for many growth phenotypes and its signaling
      is regulated by a number of molecules, including members of the suppressor of
      cytokine signaling (SOCS) family, in particular SOCS2. GH and SOCS2 have recently
      been shown to regulate neuronal differentiation by controlling expression of a
      neurogenic transcription factor, Neurogenin-1. Furthermore, SOCS2 regulates
      neurite outgrowth from neurons. Together, GH and SOCS2 play a role in regulating
      the numbers and types of neurons formed during development, as well as the
      connections they make in the central nervous system. This review will explore the
      possibility that an alteration in the balance of GH and SOCS2 may therefore lead
      to neural defects and some possible mechanisms will be examined.

PMID- 16429113
TI  - Neurodevelopmental consequences of being born SGA.
AB  - Fetal growth retardation is associated with postnatal growth retardation and
      cardio-vascular and metabolic problems later on in life. Less well described are
      the consequences of neurodevelopmental outcome. The term SGA is associated with
      mild to moderate school problems, still present in late puberty and with lower
      psychological and intellectual performance in young adulthood as compared with
      AGA controls. Also after preterm SGA birth, neurodevelopmental sequelae are more
      complex than after preterm AGA birth. Recent volumetric MRI studies of the brain
      show reduced cortical grey matter volume as one of the most important features of
      fetal growth retardation. In addition, the hippocampus appears to be especially
      susceptible to the effects of placental insufficiency. Although growth hormone
      treatment of children with short stature after SGA birth has been shown to
      increase head circumference, no clinically significant psychological improvement
      has been demonstrated after growth hormone treatment to date.

PMID- 16429114
TI  - Hypoglycemia and its effects on the brain in children with type 1 diabetes
      mellitus.
AB  - The incidence studies on hypoglycemia in Type 1 Diabetes have revealed that the
      younger the child the more frequent and severe are the hypoglycemic episodes. The
      brain does not store glycogen and perform gluconeogenesis, it relies on a
      continuous supply of glucose from blood. There are several studies demonstrating
      the brain's ability to use lactate, alanine and ketone as alternative fuels yet
      there is no evidence showing that this mechanism works in diabetic individuals.
      During hypoglycemia, cerebral blood flow increases very little in children. It is
      unlikely that this mechanism alone explains the maintenance of glucose
      utilization. Up regulation of GLUT transporters may be an additional or
      alternative protective mechanism. Severe hypoglycemic episodes experienced
      particularly in early childhood can cause deterioration in neurocognitive
      functions. There are significant individual differences in terms of vulnerability
      to hypoglycemia. Adaptive responses to hypoglycemia might vary according to both
      the degree and frequency of prior hypoglycemia and the presence of structural
      brain changes induced by chronic hyperglycemia.

PMID- 16429115
TI  - Pubertal androgen therapy in boys.
AB  - Anabolic-androgenic steroids (AAS) are necessary for normal male sexual
      differentiation and development and pubertal development. Androgen therapy is
      appropriate for boys with delayed development (constitutional delay of growth and
      puberty, CDGP) as well as those with primary or secondary hypogonadism. The
      principal goal is to restore the serum testosterone (T) level to the normal range
      at each stage of adolescent development and then to the normal adult range if the
      hypogonadism is permanent. In addition the levels of dihydrotestosterone and
      estradiol should also be within the normal range. One should be able to do that
      with a wide variety of androgen preparations-injectable, implantable, and
      cutaneous patches or gels. However, during the transition from prepubertal to
      adult it is difficult to reliably deliver the relatively small doses of T
      necessary for adolescent development using any of the cutaneous preparations.
      Androgen therapy should permit normal linear growth (including the adolescent
      growth spurt), adolescent sexual development, and the attainment of normal body
      composition including lean body mass, bone and the appropriate regional
      distribution of body fat as well as the psychological development appropriate for
      the stage of adolescent development.

PMID- 16429116
TI  - Angiogenesis--an update.
AB  - Angiogenesis, the growth of new blood vessels, is an essential process occurring
      both in health and in disease. This process is regulated by a complex interaction
      of angiogenesis-stimulating growth factors and by angiogenesis inhibitors. This
      review describes the underlying mechanisms and principles of angiogenesis, and
      summarizes its role in several pediatric topics as the retinopathy of
      prematurity, aseptic osteonecrosis, hemangiomas and vascular malformations and
      its role in pediatric malignancies.

PMID- 16429117
TI  - Angiopoietins and Tie2 in health and disease.
AB  - The angiopoietins are a class of growth factors that activate the Tie2 receptor
      and play important roles in the regulation of angiogenesis. Proper regulation of
      angiogenesis is required for both embryonic vascular development and
      physiological processes in the adult such as wound healing and the female
      reproductive cycle, while aberrant regulation of angiogenesis contributes to a
      number of pathological conditions. As a result, an increasing amount of attention
      has been directed toward analysis of the expression and function of the
      angiopoietins and Tie2. Mounting evidence suggests that not only does altered
      expression of these molecules play a pivotal role in processes requiring vessel
      growth and remodeling, but has been implicated in a variety of other biological
      and pathological processes as well. These data suggest that modulation of the
      Ang/Tie2 system may prove to be a desirable therapeutic goal in the treatment of
      a diverse array of pathological conditions.

PMID- 16429119
TI  - Notch signalling in vertebrate neural development.
AB  - Signals through the Notch receptors are used throughout development to control
      cellular fate choices. Loss- and gain-of-function studies revealed both the
      pleiotropic action of the Notch signalling pathway in development and the
      potential of Notch signals as tools to influence the developmental path of
      undifferentiated cells. As we review here, Notch signalling affects the
      development of the nervous system at many different levels. Understanding the
      complex genetic circuitry that allows Notch signals to affect specific cell fates
      in a context-specific manner defines the next challenge, especially as such an
      understanding might have important implications for regenerative medicine.

PMID- 16429118
TI  - A novel mechanism of CD40-induced apoptosis of carcinoma cells involving TRAF3
      and JNK/AP-1 activation.
AB  - Membrane-presented CD40 agonists can induce apoptosis in carcinoma, but not
      normal homologous epithelial cells, whereas soluble agonists are growth
      inhibitory but not proapoptotic unless protein synthesis is blocked. Here we
      demonstrate that membrane-presented CD40 ligand (CD154) (mCD40L), but not soluble
      agonists, triggers cell death in malignant human urothelial cells via a direct
      mechanism involving rapid upregulation of TNFR-associated factor (TRAF)3 protein,
      without concomitant upregulation of TRAF3 mRNA, followed by activation of the c
      Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway and induction of
      the caspase-9/caspase-3-associated intrinsic apoptotic machinery. TRAF3 knockdown
      abrogated JNK/AP-1 activation and prevented CD40-mediated apoptosis, whereas
      restoration of CD40 expression in CD40-negative carcinoma cells restored
      apoptotic susceptibility via the TRAF3/AP-1-dependent mechanism. In normal human
      urothelial cells, mCD40L did not trigger apoptosis, but induced rapid
      downregulation of TRAF2 and 3, thereby paralleling the situation in B
      lymphocytes. Thus, TRAF3 stabilization, JNK activation and caspase-9 induction
      define a novel pathway of CD40-mediated apoptosis in carcinoma cells.

PMID- 16429120
TI  - Mechanisms of ventral patterning in the vertebrate nervous system.
AB  - Dorsoventral patterning of the neural tube has a crucial role in shaping the
      functional organization of the CNS. It is well established that hedgehog
      signalling plays a key role in specifying ventral cell types throughout the
      neuroectoderm, and major progress has been made in elucidating how hedgehog
      signalling works in this ventral specification. In addition, other molecular
      pathways, including nodal, retinoic acid and fibroblast growth factor signalling,
      have been identified as important molecular cues for ventral patterning of the
      spinal cord, telencephalon and eye. Here, we discuss recent advances in this
      field, highlighting the emerging interplay of these signalling pathways in the
      molecular specification of ventral patterning at different rostrocaudal levels of
      the CNS.

PMID- 16429121
TI  - The molecular basis for calcium-dependent axon pathfinding.
AB  - Ca(2+) signals have profound and varied effects on growth cone motility and
      guidance. Modulation of Ca(2+) influx and release from stores by guidance cues
      shapes Ca(2+) signals, which determine the activation of downstream targets.
      Although the precise molecular mechanisms that underlie distinct Ca(2+)-mediated
      effects on growth cone behaviours remain unclear, recent studies have identified
      important players in both the regulation and targets of Ca(2+) signals in growth
      cones.

PMID- 16429122
TI  - Dendritic peptide release and peptide-dependent behaviours.
AB  - Neuropeptides that are released from dendrites, such as oxytocin and vasopressin,
      function as autocrine or paracrine signals at their site of origin, but can also
      act at distant brain targets to evoke long-lasting changes in behaviour.
      Oxytocin, for instance, has profound effects on social bonding that are exerted
      at sites that richly express oxytocin receptors, but which are innervated by few,
      if any, oxytocin-containing projections. How can a prolonged, diffuse signal have
      coherent behavioural consequences? The recently demonstrated ability of
      neuropeptides to prime vesicle stores for activity-dependent release could lead
      to a temporary functional reorganization of neuronal networks harbouring specific
      peptide receptors, providing a substrate for long-lasting effects.

PMID- 16429123
TI  - New approaches to antidepressant drug discovery: beyond monoamines.
AB  - All available antidepressant medications are based on serendipitous discoveries
      of the clinical efficacy of two classes of antidepressants more than 50 years
      ago. These tricyclic and monoamine oxidase inhibitor antidepressants were
      subsequently found to promote serotonin or noradrenaline function in the brain.
      Newer agents are more specific but have the same core mechanisms of action in
      promoting these monoamine neurotransmitters. This is unfortunate, because only
      approximately 50% of individuals with depression show full remission in response
      to these mechanisms. This review summarizes the obstacles that have hindered the
      development of non-monoamine-based antidepressants, and provides a progress
      report on some of the most promising current strategies.

PMID- 16429124
TI  - The blue brain project.
AB  - IBM's Blue Gene supercomputer allows a quantum leap in the level of detail at
      which the brain can be modelled. I argue that the time is right to begin
      assimilating the wealth of data that has been accumulated over the past century
      and start building biologically accurate models of the brain from first
      principles to aid our understanding of brain function and dysfunction.

PMID- 16429125
TI  - Dynamics of hemispheric specialization and integration in the context of motor
      control.
AB  - Behavioural and neurophysiological evidence convincingly establish that the left
      hemisphere is dominant for motor skills that are carried out with either hand or
      those that require bimanual coordination. As well as this prioritization, we
      argue that specialized functions of the right hemisphere are also indispensable
      for the realization of goal-directed behaviour. As such, lateralization of motor
      function is a dynamic and multifaceted process that emerges across different
      timescales and is contingent on task- and performer-related determinants.

PMID- 16429126
TI  - Proteome survey reveals modularity of the yeast cell machinery.
AB  - Protein complexes are key molecular entities that integrate multiple gene
      products to perform cellular functions. Here we report the first genome-wide
      screen for complexes in an organism, budding yeast, using affinity purification
      and mass spectrometry. Through systematic tagging of open reading frames (ORFs),
      the majority of complexes were purified several times, suggesting screen
      saturation. The richness of the data set enabled a de novo characterization of
      the composition and organization of the cellular machinery. The ensemble of
      cellular proteins partitions into 491 complexes, of which 257 are novel, that
      differentially combine with additional attachment proteins or protein modules to
      enable a diversification of potential functions. Support for this modular
      organization of the proteome comes from integration with available data on
      expression, localization, function, evolutionary conservation, protein structure
      and binary interactions. This study provides the largest collection of physically
      determined eukaryotic cellular machines so far and a platform for biological data
      integration and modelling.

PMID- 16429127
TI  - Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts
      identifies origins of replication.
AB  - During DNA replication one or both strands transiently become single stranded:
      first at the sites where initiation of DNA synthesis occurs (known as origins of
      replication) and subsequently on the lagging strands of replication forks as
      discontinuous Okazaki fragments are generated. We report a genome-wide analysis
      of single-stranded DNA (ssDNA) formation in the presence of hydroxyurea during
      DNA replication in wild-type and checkpoint-deficient rad53 Saccharomyces
      cerevisiae cells. In wild-type cells, ssDNA was first observed at a subset of
      replication origins and later 'migrated' bi-directionally, suggesting that ssDNA
      formation is associated with continuously moving replication forks. In rad53
      cells, ssDNA was observed at virtually every known origin, but remained there
      over time, suggesting that replication forks stall. Telomeric regions seemed to
      be particularly sensitive to the loss of Rad53 checkpoint function. Replication
      origins in Schizosaccharomyces pombe were also mapped using our method.

PMID- 16429129
TI  - Vimentin function in lymphocyte adhesion and transcellular migration.
AB  - Although the adhesive interactions of leukocytes with endothelial cells are well
      understood, little is known about the detailed mechanisms underlying the actual
      migration of leukocytes across the endothelium (diapedesis). Leukocytes have been
      shown to use both paracellular and transcellular routes for transendothelial
      migration. Here we show that peripheral blood mononuclear cells (PBMCs; T- and B
      lymphocytes) preferentially use the transcellular route. The intermediate
      filaments of both endothelial cells and lymphocytes formed a highly dynamic
      anchoring structure at the site of contact between these two cell types. The
      initiation of this process was markedly reduced in vimentin-deficient (vim(-/-))
      PBMCs and endothelial cells. When compared with wild-type PBMCs, vim(-/-) PBMCs
      showed a markedly reduced capacity to home to mesenteric lymph nodes and spleen.
      Furthermore, endothelial integrity was compromised in vim(-/-) mice,
      demonstrating that intermediate filaments also regulate the barrier that governs
      leukocyte extravasation. Absence of vimentin resulted in highly aberrant
      expression and distribution of surface molecules critical for homing (ICAM-1 and
      VCAM-1 on endothelial cells and integrin-beta1 on PBMCs). These data show that
      intermediate filaments are active in lymphocyte adhesion and transmigration.

PMID- 16429128
TI  - Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM
      1 to caveola- and F-actin-rich domains.
AB  - During inflammation, leukocytes bind to the adhesion receptors ICAM-1 and VCAM-1
      on the endothelial surface before undergoing transendothelial migration, also
      called diapedesis. ICAM-1 is also involved in transendothelial migration,
      independently of its role in adhesion, but the molecular basis of this function
      is poorly understood. Here we demonstrate that, following clustering, apical ICAM
      1 translocated to caveolin-rich membrane domains close to the ends of actin
      stress fibres. In these F-actin-rich areas, ICAM-1 was internalized and
      transcytosed to the basal plasma membrane through caveolae. Human T-lymphocytes
      extended pseudopodia into endothelial cells in caveolin- and F-actin-enriched
      areas, induced local translocation of ICAM-1 and caveolin-1 to the endothelial
      basal membrane and transmigrated through transcellular passages formed by a ring
      of F-actin and caveolae. Reduction of caveolin-1 levels using RNA interference
      (RNAi) specifically decreased lymphocyte transcellular transmigration. We propose
      that the translocation of ICAM-1 to caveola- and F-actin-rich domains links the
      sequential steps of lymphocyte adhesion and transendothelial migration and
      facilitates lymphocyte migration through endothelial cells from capillaries into
      surrounding tissue.

PMID- 16429130
TI  - Regulation of ubiquitin-binding proteins by monoubiquitination.
AB  - Proteins containing ubiquitin-binding domains (UBDs) interact with ubiquitinated
      targets and regulate diverse biological processes, including endocytosis, signal
      transduction, transcription and DNA repair. Many of the UBD-containing proteins
      are also themselves monoubiquitinated, but the functional role and the mechanisms
      that underlie this modification are less well understood. Here, we demonstrate
      that monoubiquitination of the endocytic proteins Sts1, Sts2, Eps15 and Hrs
      results in intramolecular interactions between ubiquitin and their UBDs, thereby
      preventing them from binding in trans to ubiquitinated targets. Permanent
      monoubiquitination of these proteins, mimicked by the fusion of ubiquitin to
      their carboxyl termini, impairs their ability to regulate trafficking of
      ubiquitinated receptors. Moreover, we mapped the in vivo monoubiquitination site
      in Sts2 and demonstrated that its mutation enhances the Sts2-mediated effects of
      epidermal-growth-factor-receptor downregulation. We propose that
      monoubiquitination of ubiquitin-binding proteins inhibits their capacity to bind
      to and control the functions of ubiquitinated targets in vivo.

PMID- 16429132
TI  - Experience-dependent modification of mechanisms of long-term depression.
AB  - Mechanisms of long-term potentiation and depression (LTP and LTD) change
      considerably during development, but the importance of these changes and the
      factors that control them is not clear. We found that visual experience triggered
      a switch in mechanisms of LTD in rat perirhinal cortex, an area critical for
      visual recognition memory. Thus, changes in synaptic plasticity mechanisms were
      correlated with the changing physiological demands on the CNS.

PMID- 16429131
TI  - The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function
      interaction that prevents the nuclear localization of PARP-1.
AB  - The Vpr protein of HIV-1 functions as a vital accessory gene by regulating
      various cellular functions, including cell differentiation, apoptosis, nuclear
      factor of kappaB (NF-kappaB) suppression and cell-cycle arrest of the host cell.
      Several reports have indicated that Vpr complexes with the glucocorticoid
      receptor (GR), but it remains unclear whether the GR pathway is required for Vpr
      to function. Here, we report that Vpr uses the GR pathway as a recruitment
      vehicle for the NF-kappaB co-activating protein, poly(ADP-ribose) polymerase-1
      (PARP-1). The GR interaction with Vpr is both necessary and sufficient to
      facilitate this interaction by potentiating the formation of a Vpr-GR-PARP-1
      complex. The recruitment of PARP-1 by the Vpr-GR complex prevents its nuclear
      localization, which is necessary for Vpr to suppress NF-kappaB. The association
      of GR with PARP-1 is not observed with steroid (glucocorticoid) treatment,
      indicating that the GR association with PARP-1 is a gain of function that is
      solely attributed to HIV-1 Vpr. These data provide important insights into Vpr
      biology and its role in HIV pathogenesis.

PMID- 16429133
TI  - Supersensitive Ras activation in dendrites and spines revealed by two-photon
      fluorescence lifetime imaging.
AB  - To understand the biochemical signals regulated by neural activity, it is
      necessary to measure protein-protein interactions and enzymatic activity in
      neuronal microcompartments such as axons, dendrites and their spines. We combined
      two-photon excitation laser scanning with fluorescence lifetime imaging to
      measure fluorescence resonance energy transfer at high resolutions in brain
      slices. We also developed sensitive fluorescent protein-based sensors for the
      activation of the small GTPase protein Ras with slow (FRas) and fast (FRas-F)
      kinetics. Using FRas-F, we found in CA1 hippocampal neurons that trains of back
      propagating action potentials rapidly and reversibly activated Ras in dendrites
      and spines. The relationship between firing rate and Ras activation was highly
      nonlinear (Hill coefficient approximately 5). This steep dependence was caused by
      a highly cooperative interaction between calcium ions (Ca(2+)) and Ras
      activators. The Ras pathway therefore functions as a supersensitive threshold
      detector for neural activity and Ca(2+) concentration.

PMID- 16429134
TI  - Activity in prefrontal cortex during dynamic selection of action sequences.
AB  - Completing everyday tasks often requires the execution of action sequences
      matched to a particular problem. To study the neural processes underlying these
      behaviors, we trained monkeys to produce a series of eye movements according to a
      sequence that changed unpredictably from one block of trials to the next. We then
      applied a decoding algorithm to estimate which sequence was being represented by
      the ensemble activity in prefrontal cortex. We found that the sequence predicted
      by this analysis changed gradually from the sequence that had been correct in the
      previous block to the sequence that was correct in the current block, closely
      following the fraction of executed movements that were consistent with the
      corresponding sequence. Thus, the neural activity dynamically tracked the
      monkeys' uncertainty about the correct sequence of actions. These results are
      consistent with prefrontal involvement in representing subjective knowledge of
      the correct action sequence.

PMID- 16429135
TI  - A role for cardiotrophin-like cytokine in the circadian control of mammalian
      locomotor activity.
AB  - The suprachiasmatic nucleus (SCN) drives circadian rhythms of locomotor behavior
      by releasing factors that act on receptor sites near the third ventricle. Here we
      show that cardiotrophin-like cytokine (CLC) satisfies multiple criteria for a
      circadian regulator of locomotor activity. In the mouse, CLC is expressed in a
      subpopulation of SCN vasopressin neurons with a circadian rhythm that peaks
      during the daily period of locomotor quiescence. CLC receptors flank the third
      ventricle, and acute infusion of CLC into the third ventricle produced a
      transient blockade of locomotor activity without affecting the circadian clock.
      The hypothalamic infusion of neutralizing antibodies to the CLC receptor produced
      extra daily locomotor activity at the time when CLC is maximally expressed. These
      results suggest that CLC is probably an SCN output signal important for shaping
      daily rhythms of behavior; moreover, they indicate an unexpected role for a
      cytokine in adult brain function.

PMID- 16429136
TI  - The Runx1/AML1 transcription factor selectively regulates development and
      survival of TrkA nociceptive sensory neurons.
AB  - Neural crest cells (NCCs) can adopt different neuronal fates. In NCCs, neurogenin
      2 promotes sensory specification but does not specify different subclasses of
      sensory neurons. Understanding the gene cascades that direct Trk gene activation
      may reveal mechanisms generating sensory diversity, because different Trks are
      expressed in different sensory neuron subpopulations. Here we show in chick and
      mouse that the Runt transcription factor Runx1 promotes axonal growth, is
      selectively expressed in neural crest-derived TrkA(+) sensory neurons and
      mediates TrkA transactivation in migratory NCCs. Inhibition of Runt activity
      depletes TrkA expression and leads to neuronal death. Moreover, Runx1
      overexpression is incompatible with multipotency in the migratory neural crest
      but does not induce expression of pan-neuronal genes. Instead, Runx1-induced
      neuronal differentiation depends on an existing neurogenin2 proneural gene
      program. Our data show that Runx1 directs, in a context-dependent manner, key
      aspects of the establishment of the TrkA(+) nociceptive subclass of neurons.

PMID- 16429137
TI  - Netrins guide Drosophila commissural axons at short range.
AB  - Netrins are secreted axon guidance molecules required for commissure formation in
      a wide range of animal species, including Caenorhabditis elegans, Drosophila
      melanogaster and mice. They are generally thought to function as
      chemoattractants, acting at a distance to direct commissural axon growth toward
      the midline of the central nervous system. We show here, however, that D.
      melanogaster commissural axons still orient normally and reach the midline even
      in the complete absence of netrins, though some of them fail to cross the
      midline. Tethering endogenous netrin to the membrane selectively disrupts its
      long-range but not short-range activity, yet still allows normal commissure
      formation. We therefore propose that netrins act in commissural axon guidance as
      short-range cues that promote midline crossing, not as long-range
      chemoattractants.

PMID- 16429138
TI  - Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class
      switching in bystander B cells.
AB  - Immunoglobulin class switching from immunoglobulin M (IgM) to IgG and IgA is
      central to immunity against viruses and requires the activation of B cells by T
      cells via CD154 (CD40 ligand) and cytokines. These molecules limit their
      signaling activity in immune cells by turning on negative feedback proteins,
      including IkappaB and SOCS. We show here that negative factor (Nef) protein, an
      immunosuppressive human immunodeficiency virus 1 protein expressed and released
      by infected cells, penetrates B cells both in vivo and in vitro. Nef suppressed
      immunoglobulin class-switch DNA recombination by inducing IkappaBalpha and SOCS
      proteins, which blocked CD154 and cytokine signaling via NF-kappaB and STAT
      transcription factors. Thus, human immunodeficiency virus 1 may evade protective
      T cell-dependent IgG and IgA responses by 'hijacking' physiological feedback
      inhibitors in B cells via Nef.

PMID- 16429139
TI  - Identification of a B-1 B cell-specified progenitor.
AB  - The B-1 subpopulation of B lymphocytes differs phenotypically and functionally
      from conventional B-2 B cells. B-1 B cells are proposed to derive from a distinct
      progenitor, but such a population has not been isolated. Here we identify and
      characterize a B-1 B cell progenitor whose numbers peaked in fetal bone marrow
      but were less abundant in postnatal bone marrow. These Lin(-)CD45R(lo-neg)CD19(+)
      cells responded to thymic stromal lymphopoietin and 'preferentially'
      reconstituted functional sIgM(hi)CD11b(+)CD5(lo-neg) B-1 B cells, but not
      sIgM(+)CD11b(-) B-2 B cells, in vivo. These data indicate that the CD45R(lo
      neg)CD19(+) population includes B-1 B cell-specified progenitors and support
      models proposing distinct developmental pathways for B-1 B cells.

PMID- 16429140
TI  - Self-organization in phase separation of a lyotropic liquid crystal into
      cellular, network and droplet morphologies.
AB  - Phase separation is one of the most fundamental physical phenomena that controls
      the morphology of heterogeneous structures. Phase separation of a binary mixture
      of simple liquids produces only two morphologies: a bicontinuous or a droplet
      structure in the case of a symmetric or an asymmetric composition, respectively.
      For complex fluids, there is a possibility to produce other interesting
      morphologies. We found that a network structure of the minority phase can also be
      induced transiently on phase separation if the dynamics of the minority phase are
      much slower than those of the majority phase. Here we induce a cellular structure
      of the minority phase intentionally with the help of its smectic ordering, using
      phase separation of a lyotropic liquid crystal into the isotropic and smectic
      phase. We can control the three morphologies, cellular, network and droplet
      structures, solely by changing the heating rate. We demonstrate that the kinetic
      interplay between phase separation and smectic ordering is a key to the
      morphological selection. This may provide a new route to the formation of network
      and cellular morphologies in soft materials.

PMID- 16429142
TI  - Photosensitive gold-nanoparticle-embedded dielectric nanowires.
AB  - Noble-metal nanoparticles embedded in dielectric matrices are considered to have
      practical applications in ultrafast all-optical switching devices owing to their
      enhanced third-order nonlinear susceptibility, especially near the surface
      plasmon-resonance (SPR) frequency. Here we present the use of a microreactor
      approach to the fabrication of a self-organized photosensitive gold nanoparticle
      chain encapsulated in a dielectric nanowire. Such a hybrid nanowire shows
      pronounced SPR absorption. More remarkably, a strong wavelength-dependent and
      reversible photoresponse has been demonstrated in a two-terminal device using an
      ensemble of gold nanopeapodded silica nanowires under light illumination, whereas
      no photoresponse was observed for the plain silica nanowires. These results show
      the potential of using gold nanopeapodded silica nanowires as wavelength
      controlled optical nanoswitches. The microreactor approach can be applied to the
      preparation of a range of hybrid metal-dielectric one-dimensional nanostructures
      that can be used as functional building blocks for nanoscale waveguiding devices,
      sensors and optoelectronics.

PMID- 16429143
TI  - Optical trapping and integration of semiconductor nanowire assemblies in water.
AB  - Semiconductor nanowires have received much attention owing to their potential use
      as building blocks of miniaturized electrical, nanofluidic and optical devices.
      Although chemical nanowire synthesis procedures have matured and now yield
      nanowires with specific compositions and growth directions, the use of these
      materials in scientific, biomedical and microelectronic applications is greatly
      restricted owing to a lack of methods to assemble nanowires into complex
      heterostructures with high spatial and angular precision. Here we show that an
      infrared single-beam optical trap can be used to individually trap, transfer and
      assemble high-aspect-ratio semiconductor nanowires into arbitrary structures in a
      fluid environment. Nanowires with diameters as small as 20 nm and aspect ratios
      of more than 100 can be trapped and transported in three dimensions, enabling the
      construction of nanowire architectures that may function as active photonic
      devices. Moreover, nanowire structures can now be assembled in physiological
      environments, offering new forms of chemical, mechanical and optical stimulation
      of living cells.

PMID- 16429144
TI  - Quantitative imaging of Plasmodium transmission from mosquito to mammal.
AB  - Plasmodium, the parasite that causes malaria, is transmitted by a mosquito into
      the dermis and must reach the liver before infecting erythrocytes and causing
      disease. We present here a quantitative, real-time analysis of the fate of
      parasites transmitted in a rodent system. We show that only a proportion of the
      parasites enter blood capillaries, whereas others are drained by lymphatics.
      Lymph sporozoites stop at the proximal lymph node, where most are degraded inside
      dendritic leucocytes, but some can partially differentiate into exoerythrocytic
      stages. This previously unrecognized step of the parasite life cycle could
      influence the immune response of the host, and may have implications for
      vaccination strategies against the preerythrocytic stages of the parasite.

PMID- 16429145
TI  - Histidine button engineered into cardiac troponin I protects the ischemic and
      failing heart.
AB  - The myofilament protein troponin I (TnI) has a key isoform-dependent role in the
      development of contractile failure during acidosis and ischemia. Here we show
      that cardiac performance in vitro and in vivo is enhanced when a single histidine
      residue present in the fetal cardiac TnI isoform is substituted into the adult
      cardiac TnI isoform at codon 164. The most marked effects are observed under the
      acute challenges of acidosis, hypoxia, ischemia and ischemia-reperfusion, in
      chronic heart failure in transgenic mice and in myocytes from failing human
      hearts. In the isolated heart, histidine-modified TnI improves systolic and
      diastolic function and mitigates reperfusion-associated ventricular arrhythmias.
      Cardiac performance is markedly enhanced in transgenic hearts during reperfusion
      despite a high-energy phosphate content similar to that in nontransgenic hearts,
      providing evidence for greater energetic economy. This pH-sensitive 'histidine
      button' engineered in TnI produces a titratable molecular switch that 'senses'
      changes in the intracellular milieu of the cardiac myocyte and responds by
      preferentially augmenting acute and long-term function under pathophysiological
      conditions. Myofilament-based inotropy may represent a therapeutic avenue to
      improve myocardial performance in the ischemic and failing heart.

PMID- 16429146
TI  - Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem
      cells.
AB  - Successful ex vivo expansion of hematopoietic stem cells (HSCs) would greatly
      benefit the treatment of disease and the understanding of crucial questions of
      stem cell biology. Here we show, using microarray studies, that the HSC
      supportive mouse fetal liver CD3(+) cells specifically express the proteins
      angiopoietin-like 2 (Angptl2) and angiopoietin-like 3 (Angptl3). We observed a 24
      or 30-fold net expansion of long-term HSCs by reconstitution analysis when we
      cultured highly enriched HSCs for 10 days in the presence of Angptl2 or Angptl3
      together with saturating levels of other growth factors. The coiled-coil domain
      of Angptl2 was capable of stimulating expansion of HSCs. Furthermore,
      angiopoietin-like 5, angiopoietin-like 7 and microfibril-associated glycoprotein
      4 also supported expansion of HSCs in culture.

PMID- 16429147
TI  - An explosive-degrading cytochrome P450 activity and its targeted application for
      the phytoremediation of RDX.
AB  - The widespread presence in the environment of hexahydro-1,3,5-trinitro-1,3,5
      triazine (RDX), one of the most widely used military explosives, has raised
      concern owing to its toxicity and recalcitrance to degradation. To investigate
      the potential of plants to remove RDX from contaminated soil and water, we
      engineered Arabidopsis thaliana to express a bacterial gene xplA encoding an RDX
      degrading cytochrome P450 (ref. 1). We demonstrate that the P450 domain of XplA
      is fused to a flavodoxin redox partner and catalyzes the degradation of RDX in
      the absence of oxygen. Transgenic A. thaliana expressing xplA removed and
      detoxified RDX from liquid media. As a model system for RDX phytoremediation, A.
      thaliana expressing xplA was grown in RDX-contaminated soil and found to be
      resistant to RDX phytotoxicity, producing shoot and root biomasses greater than
      those of wild-type plants. Our work suggests that expression of xplA in landscape
      plants may provide a suitable remediation strategy for sites contaminated by this
      class of explosives.

PMID- 16429148
TI  - Directed evolution of adeno-associated virus yields enhanced gene delivery
      vectors.
AB  - Adeno-associated viral vectors are highly safe and efficient gene delivery
      vehicles. However, numerous challenges in vector design remain, including
      neutralizing antibody responses, tissue transport and infection of resistant cell
      types. Changes must be made to the viral capsid to overcome these problems;
      however, very often insufficient information is available for rational design of
      improvements. We therefore applied a directed evolution approach involving the
      generation of large mutant capsid libraries and selection of adeno-associated
      virus (AAV) 2 variants with enhanced properties. High-throughput selection
      processes were designed to isolate mutants within the library with altered
      affinities for heparin or the ability to evade antibody neutralization and
      deliver genes more efficiently than wild-type capsid in the presence of anti-AAV
      serum. This approach, which can be extended to additional gene delivery
      challenges and serotypes, directs viral evolution to generate 'designer' gene
      delivery vectors with specified, enhanced properties.

PMID- 16429149
TI  - Optimization of humanized IgGs in glycoengineered Pichia pastoris.
AB  - As the fastest growing class of therapeutic proteins, monoclonal antibodies
      (mAbs) represent a major potential drug class. Human antibodies are glycosylated
      in their native state and all clinically approved mAbs are produced by mammalian
      cell lines, which secrete mAbs with glycosylation structures that are similar,
      but not identical, to their human counterparts. Glycosylation of mAbs influences
      their interaction with immune effector cells that kill antibody-targeted cells.
      Here we demonstrate that human antibodies with specific human N-glycan structures
      can be produced in glycoengineered lines of the yeast Pichia pastoris and that
      antibody-mediated effector functions can be optimized by generating specific
      glycoforms. Glycoengineered P. pastoris provides a general platform for producing
      recombinant antibodies with human N-glycosylation.

PMID- 16429150
TI  - Identification and evolution of dual-topology membrane proteins.
AB  - Integral membrane proteins are generally believed to have unique membrane
      topologies. However, it has been suggested that dual-topology proteins that adopt
      a mixture of two opposite orientations in the membrane may exist. Here we show
      that the membrane orientations of five dual-topology candidates identified in
      Escherichia coli are highly sensitive to changes in the distribution of
      positively charged residues, that genes in families containing dual-topology
      candidates occur in genomes either as pairs or as singletons and that gene pairs
      encode two oppositely oriented proteins whereas singletons encode dual-topology
      candidates. Our results provide strong support for the existence of dual-topology
      proteins and shed new light on the evolution of membrane-protein topology and
      structure.

PMID- 16429151
TI  - Sequence-specific recognition of RNA hairpins by the SAM domain of Vts1p.
AB  - The SAM domain of the Saccharomyces cerevisiae post-transcriptional regulator
      Vts1p epitomizes a subfamily of SAM domains conserved from yeast to humans that
      function as sequence-specific RNA-binding domains. Here we report the 2.0-A X-ray
      structure of the Vts1p SAM domain bound to a high-affinity RNA ligand.
      Specificity of RNA binding arises from the association of a guanosine loop base
      with a shallow pocket on the SAM domain and from multiple SAM domain contacts to
      the unique backbone structure of the loop, defined in part by a nonplanar base
      pair within the loop. We have validated NNF1 as an endogenous target of Vts1p
      among 79 transcripts that copurify with Vts1p. Bioinformatic analysis of these
      mRNAs demonstrates that the RNA-binding specificity of Vts1p in vivo is probably
      more stringent than that of the isolated SAM domain in vitro.

PMID- 16429153
TI  - Activator-specific recruitment of Mediator in vivo.
AB  - The Mediator complex associates with eukaryotic RNA polymerase (Pol) II and is
      recruited to transcriptional enhancers by activator proteins. It is believed that
      Mediator is a general component of the Pol II machinery that is crucial to
      connect enhancer-bound activators to basic transcription factors. However, we
      show that Mediator does not detectably associate with many highly active Pol II
      promoters in yeast cells. Furthermore, in response to stress conditions, Mediator
      association is not directly related to Pol II association and in some cases is
      not detectable at highly activated promoters. Thus, Mediator is recruited to
      enhancers in an activator-specific manner, and it does not seem to be a
      stoichiometric component of the basic Pol II machinery in vivo. Mediator is
      recruited by many activators involved in stress responses, but not by the major
      activators that function under optimal conditions.

PMID- 16429152
TI  - Direct ribosomal binding by a cellular inhibitor of translation.
AB  - During apoptosis and under conditions of cellular stress, several signaling
      pathways promote inhibition of cap-dependent translation while allowing continued
      translation of specific messenger RNAs encoding regulatory and stress-response
      proteins. We report here that the apoptotic regulator Reaper inhibits protein
      synthesis by binding directly to the 40S ribosomal subunit. This interaction does
      not affect either ribosomal association of initiation factors or formation of 43S
      or 48S complexes. Rather, it interferes with late initiation events upstream of
      60S subunit joining, apparently modulating start-codon recognition during
      scanning. CrPV IRES-driven translation, involving direct ribosomal recruitment to
      the start site, is relatively insensitive to Reaper. Thus, Reaper is the first
      known cellular ribosomal binding factor with the potential to allow selective
      translation of mRNAs initiating at alternative start codons or from certain IRES
      elements. This function of Reaper may modulate gene expression programs to affect
      cell fate.

PMID- 16429154
TI  - Allosteric signaling of ATP hydrolysis in GroEL-GroES complexes.
AB  - The double-ring chaperonin GroEL and its lid-like cochaperonin GroES form
      asymmetric complexes that, in the ATP-bound state, mediate productive folding in
      a hydrophilic, GroES-encapsulated chamber, the so-called cis cavity. Upon ATP
      hydrolysis within the cis ring, the asymmetric complex becomes able to accept non
      native polypeptides and ATP in the open, trans ring. Here we have examined the
      structural basis for this allosteric switch in activity by cryo-EM and single
      particle image processing. ATP hydrolysis does not change the conformation of the
      cis ring, but its effects are transmitted through an inter-ring contact and cause
      domain rotations in the mobile trans ring. These rigid-body movements in the
      trans ring lead to disruption of its intra-ring contacts, expansion of the entire
      ring and opening of both the nucleotide pocket and the substrate-binding domains,
      admitting ATP and new substrate protein.

PMID- 16429155
TI  - RNA recognition by the Vts1p SAM domain.
AB  - The putative yeast post-transcriptional regulator Vts1p and its related protein
      Smaug, from Drosophila melanogaster, each use a sterile alpha motif (SAM) domain
      to bind an RNA hairpin termed the Smaug recognition element (SRE). Here, we
      present the NMR structures of the Vts1p-SRE complex and the free SRE. Structural
      highlights include the direct recognition of a guanine base and the formation or
      stabilization of a base pair in the SRE loop.

PMID- 16429156
TI  - Shape-specific recognition in the structure of the Vts1p SAM domain with RNA.
AB  - Although the abundant sterile alpha motif (SAM) domain was originally classified
      as a protein-protein interaction domain, it has recently been shown that certain
      SAM domains have the ability to bind RNA, defining a new type of post
      transcriptional gene regulator. To further understand the function of SAM-RNA
      recognition, we determined the solution structures of the SAM domain of the
      Saccharomyces cerevisiae Vts1p (Vts1p-SAM) and the Smaug response element (SRE)
      stem-loop RNA as a complex and in isolation. The structures show that Vts1p-SAM
      recognizes predominantly the shape of the SRE rather than its sequence, with the
      exception of a G located at the tip of the pentaloop. Using microarray gene
      profiling, we identified several genes in S. cerevisiae that seem to be regulated
      by Vts1p and contain one or more copies of the SRE.

PMID- 16429157
TI  - Spectrin mutations cause spinocerebellar ataxia type 5.
AB  - We have discovered that beta-III spectrin (SPTBN2) mutations cause
      spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred
      descended from President Lincoln's grandparents and two additional families. Two
      families have separate in-frame deletions of 39 and 15 bp, and a third family has
      a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly
      expressed in Purkinje cells and has been shown to stabilize the glutamate
      transporter EAAT4 at the surface of the plasma membrane. We found marked
      differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in
      SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not
      mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin
      mutations are a previously unknown cause of ataxia and neurodegenerative disease
      that affect membrane proteins involved in glutamate signaling.

PMID- 16429158
TI  - Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in
      dominant intermediate Charcot-Marie-Tooth neuropathy.
AB  - Charcot-Marie-Tooth (CMT) neuropathies are common disorders of the peripheral
      nervous system caused by demyelination or axonal degeneration, or a combination
      of both features. We previously assigned the locus for autosomal dominant
      intermediate CMT neuropathy type C (DI-CMTC) to chromosome 1p34-p35. Here we
      identify two heterozygous missense mutations (G41R and E196K) and one de novo
      deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated
      families affected with DI-CMTC. Biochemical experiments and genetic
      complementation in yeast show partial loss of aminoacylation activity of the
      mutant proteins, and mutations in YARS, or in its yeast ortholog TYS1, reduce
      yeast growth. YARS localizes to axonal termini in differentiating primary motor
      neuron and neuroblastoma cultures. This specific distribution is significantly
      reduced in cells expressing mutant YARS proteins. YARS is the second aminoacyl
      tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing
      complexes with neurodegeneration.

PMID- 16429159
TI  - The sex-specific genetic architecture of quantitative traits in humans.
AB  - Mapping genetically complex traits remains one of the greatest challenges in
      human genetics today. In particular, gene-environment and gene-gene interactions,
      genetic heterogeneity and incomplete penetrance make thorough genetic dissection
      of complex traits difficult, if not impossible. Sex could be considered an
      environmental factor that can modify both penetrance and expressivity of a wide
      variety of traits. Sex is easily determined and has measurable effects on
      recognizable morphology; neurobiological circuits; susceptibility to autoimmune
      disease, diabetes, asthma, cardiovascular and psychiatric disease; and
      quantitative traits like blood pressure, obesity and lipid levels, among others.
      In this study, we evaluated sex-specific heritability and genome-wide linkages
      for 17 quantitative traits in the Hutterites. The results of this study could
      have important implications for mapping complex trait genes.

PMID- 16429160
TI  - Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin.
AB  - The pathogenesis of Bacillus anthracis, the bacterium that causes anthrax,
      depends on secretion of three factors that combine to form two bipartite toxins.
      Edema toxin, consisting of protective antigen (PA) and edema factor (EF), causes
      the edema associated with cutaneous anthrax infections, whereas lethal toxin
      (LeTx), consisting of PA and lethal factor (LF), is believed to be responsible
      for causing death in systemic anthrax infections. EF and LF can be transported by
      PA into the cytosol of many cell types. In mouse macrophages, LF can cause rapid
      necrosis that may be related to the pathology of systemic infections. Inbred
      mouse strains display variable sensitivity to LeTx-induced macrophage necrosis.
      This trait difference has been mapped to a locus on chromosome 11 named Ltxs1
      (refs. 7,8). Here we show that an extremely polymorphic gene in this locus,
      Nalp1b, is the primary mediator of mouse macrophage susceptibility to LeTx. We
      also show that LeTx-induced macrophage death requires caspase-1, which is
      activated in susceptible, but not resistant, macrophages after intoxication,
      suggesting that Nalp1b directly or indirectly activates caspase-1 in response to
      LeTx.

PMID- 16429161
TI  - Induction, suppression and requirement of RNA silencing pathways in virulent
      Agrobacterium tumefaciens infections.
AB  - Regulation of gene expression through microRNAs (miRNAs) and antiviral defense
      through small interfering RNAs (siRNAs) are aspects of RNA silencing, a process
      originally discovered as an unintended consequence of plant transformation by
      disarmed Agrobacterium tumefaciens strains. Although RNA silencing protects cells
      against foreign genetic elements, its defensive role against virulent, tumor
      inducing bacteria has remained unexplored. Here, we show that siRNAs
      corresponding to transferred-DNA oncogenes initially accumulate in virulent A.
      tumefaciens-infected tissues and that RNA interference-deficient plants are
      hypersusceptible to the pathogen. Successful infection relies on a potent
      antisilencing state established in tumors whereby siRNA synthesis is specifically
      inhibited. This inhibition has only modest side effects on the miRNA pathway,
      shown here to be essential for disease development. The similarities and
      specificities of the A. tumefaciens RNA silencing interaction are discussed and
      contrasted with the situation encountered with plant viruses.

PMID- 16429162
TI  - Evaluating potential for whole-genome studies in Kosrae, an isolated population
      in Micronesia.
AB  - Whole-genome association studies are predicted to be especially powerful in
      isolated populations owing to increased linkage disequilibrium (LD) and decreased
      allelic diversity, but this possibility has not been empirically tested. We
      compared genome-wide data on 113,240 SNPs typed on 30 trios from the Pacific
      island of Kosrae to the same markers typed in the 270 samples from the
      International HapMap Project. The extent of LD is longer and haplotype diversity
      is lower in Kosrae than in the HapMap populations. More than 98% of Kosraen
      haplotypes are present in HapMap populations, indicating that HapMap will be
      useful for genetic studies on Kosrae. The long-range LD around common alleles and
      limited diversity result in improved efficiency in genetic studies in this
      population and augments the power to detect association of 'hidden SNPs'.

PMID- 16429163
TI  - Control of filamentous fungal cell shape by septins and formins.
AB  - Studies in various model systems have identified two protein families that are
      crucial for shaping cell morphology: the septins and the formins. Both families
      are conserved in most eukaryotes, but the functions and regulation of individual
      homologues can vary depending on their precise cellular context. The rich array
      of cell geometries found in different filamentous fungal species provides a
      powerful experimental canvas for studying the evolution and regulation of septins
      and formins. Here, I assimilate what is known about the function of these protein
      families in filamentous fungi and propose that further studies in these organisms
      could answer some open mechanistic questions that pertain in general to
      eukaryotic cells.

PMID- 16429164
TI  - Harnessing natural diversity to probe metabolic pathways.
AB  - Analyses of cellular processes in the yeast Saccharomyces cerevisiae rely
      primarily upon a small number of highly domesticated laboratory strains, leaving
      the extensive natural genetic diversity of the model organism largely unexplored
      and unexploited. We asked if this diversity could be used to enrich our
      understanding of basic biological processes. As a test case, we examined a simple
      trait: the utilization of di/tripeptides as nitrogen sources. The capacity to
      import small peptides is likely to be under opposing selective pressures
      (nutrient utilization versus toxin vulnerability) and may therefore be sculpted
      by diverse pathways and strategies. Hitherto, dipeptide utilization in S.
      cerevisiae was solely ascribed to the activity of a single protein, the Ptr2p
      transporter. Using high-throughput phenotyping and several genetically diverse
      strains, we identified previously unknown cellular activities that contribute to
      this trait. We find that the Dal5p allantoate/ureidosuccinate permease is also
      capable of facilitating di/tripeptide transport. Moreover, even in the absence of
      Dal5p and Ptr2p, an additional activity--almost certainly the periplasmic
      asparaginase II Asp3p--facilitates the utilization of dipeptides with C-terminal
      asparagine residues by a different strategy. Another, as-yet-unidentified
      activity enables the utilization of dipeptides with C-terminal arginine residues.
      The relative contributions of these activities to the utilization of
      di/tripeptides vary among the strains analyzed, as does the vulnerability of
      these strains to a toxic dipeptide. Only by sampling the genetic diversity of
      multiple strains were we able to uncover several previously unrecognized layers
      of complexity in this metabolic pathway. High-throughput phenotyping facilitates
      the rapid exploration of the molecular basis of biological complexity, allowing
      for future detailed investigation of the selective pressures that drive microbial
      evolution.

PMID- 16429167
TI  - The application of manganese complexes of ligands derived from 1,4,7
      triazacyclononane in oxidative catalysis.
AB  - Since the disclosure that manganese complexes of certain azamacrocyclic ligands
      were potent low-temperature bleaching catalysts, considerable effort has focussed
      on their development towards the efficient catalytic oxidation of other
      substrates, principally with the environmentally benign oxidant H(2)O(2). These
      efforts have resulted in a broad substrate scope for the system, including
      alkenes (to give both epoxides and cis-diols as potential products), alcohols,
      sulfides and C-H oxidation. Additional developments include the heterogenisation
      of catalytic systems as well as the first generation of enantiomerically pure
      ligand systems for application in asymmetric epoxidation catalysis. To date there
      has only been modest success in this regard, but as our understanding of the
      nature of the active oxidant(s) continues to develop it is likely that there will
      be viable applications for these systems in the near future.

PMID- 16429165
TI  - Differential susceptibility to hypertension is due to selection during the out-of
      Africa expansion.
AB  - Hypertension is a leading cause of stroke, heart disease, and kidney failure. The
      genetic basis of blood pressure variation is largely unknown but is likely to
      involve genes that influence renal salt handling and arterial vessel tone. Here
      we argue that susceptibility to hypertension is ancestral and that differential
      susceptibility to hypertension is due to differential exposure to selection
      pressures during the out-of-Africa expansion. The most important selection
      pressure was climate, which produced a latitudinal cline in heat adaptation and,
      therefore, hypertension susceptibility. Consistent with this hypothesis, we show
      that ecological variables, such as latitude, temperature, and rainfall, explain
      worldwide variation in heat adaptation as defined by seven functional alleles in
      five genes involved in blood pressure regulation. The latitudinal cline in heat
      adaptation is consistent worldwide and is largely unmatched by latitudinal clines
      in short tandem repeat markers, control single nucleotide polymorphisms, or non
      functional single nucleotide polymorphisms within the five genes. In addition, we
      show that latitude and one of these alleles, GNB3 (G protein beta3 subunit) 825T,
      account for a major portion of worldwide variation in blood pressure. These
      results suggest that the current epidemic of hypertension is due to exposures of
      the modern period interacting with ancestral susceptibility. Modern populations
      differ in susceptibility to these new exposures, however, such that those from
      hot environments are more susceptible to hypertension than populations from cold
      environments. This differential susceptibility is likely due to our history of
      adaptation to climate.

PMID- 16429168
TI  - Two complexes of copper(II) salts with 5-amino-3-(pyrid-2-yl)-1H-pyrazole, the
      prototype for a new class of ditopic ligand.
AB  - The title ligand ('L') in crystalline [CuBrL(2)]Br.CH(3)OH and
      [Cu(OH(2))L(2)]SO(4).H(2)O.CH(3)OH chelates to both the copper(II) cations and
      the charge-balancing anions.

PMID- 16429166
TI  - Accurate prediction of the functional significance of single nucleotide
      polymorphisms and mutations in the ABCA1 gene.
AB  - The human genome contains an estimated 100,000 to 300,000 DNA variants that alter
      an amino acid in an encoded protein. However, our ability to predict which of
      these variants are functionally significant is limited. We used a bioinformatics
      approach to define the functional significance of genetic variation in the ABCA1
      gene, a cholesterol transporter crucial for the metabolism of high density
      lipoprotein cholesterol. To predict the functional consequence of each coding
      single nucleotide polymorphism and mutation in this gene, we calculated a
      substitution position-specific evolutionary conservation score for each variant,
      which considers site-specific variation among evolutionarily related proteins. To
      test the bioinformatics predictions experimentally, we evaluated the biochemical
      consequence of these sequence variants by examining the ability of cell lines
      stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our
      bioinformatics approach correctly predicted the functional impact of greater than
      94% of the naturally occurring variants we assessed. The bioinformatics
      predictions were significantly correlated with the degree of functional
      impairment of ABCA1 mutations (r2 = 0.62, p = 0.0008). These results have allowed
      us to define the impact of genetic variation on ABCA1 function and to suggest
      that the in silico evolutionary approach we used may be a useful tool in general
      for predicting the effects of DNA variation on gene function. In addition, our
      data suggest that considering patterns of positive selection, along with patterns
      of negative selection such as evolutionary conservation, may improve our ability
      to predict the functional effects of amino acid variation.

PMID- 16429169
TI  - Synthesis of a series of 4-pyridyl-1,2,4-triazole-containing cadmium(II)
      luminescent complexes.
AB  - Using two 4-substitued triazole ligands, 4-(pyrid-2-yl)-1,2,4-triazole (L(1)) and
      4-(pyrid-3-yl)-1,2,4-triazole (L(2)), a series of novel triazole-cadmium(II)
      complexes varying from zero- to three-dimensional have been prepared and their
      crystal structures determined via single-crystal X-ray diffraction.
      [Cd(2)(micro(2)-L(1))(3)(L(1))(2)(NO(3))(mu(2)
      NO(3))(H(2)O)(2)](NO(3))(2).1.75H(2)O (1) is a binuclear complex containing
      bidendate, monodedate and free nitrate anions. When the bridging anions SCN(-)
      and dca (dca = N(CN)(2)(-)) were added to the reaction system of 1, one
      dimensional (1D) [Cd(L(1))(2)(NCS)(2)](n) (2) and two-dimensional (2D)
      [Cd(L(1))(2)(dca)(2)](n) (3) were isolated, respectively. When L(2) instead of
      L(1) was used, [Cd(L(2))(2)(NCS)(2)(H(2)O)(2)] (4) and 1D
      [Cd(L(2))(2)(dca)(2)](n) (5) were obtained. When the ratio of Cd to L(2) was
      changed from 1:2 to 1:1 in the reaction system of 5, three-dimensional (3D)
      {[Cd(3)(micro(2)-L(2))(3)(dca)(6)].0.75H(2)O}(n) (6) with 1D microporous channels
      along the a direction was isolated. Further investigations on other Cd(ii) salts
      and the L(2) ligand in a Cd to L(2) ratio of 1:1, an unexpected complex [Cd(mu(2)
      L(2))(mu(3)-SO(4))(H(2)O)](n) (7) with a 3D open framework was obtained. All of
      the complexes exhibit strong blue fluorescence emission bands in the solid state
      at ambient temperature, of which the excitation and emission maxima are red
      shifted to longer wavelength as compared to those in water. Powder X-ray
      diffraction and thermal studies were used to investigate the bulk nature of the
      3D coordination polymers 6 and 7.

PMID- 16429170
TI  - Lanthanide hydroxide cubane clusters anchoring ferrocenes: model compounds for
      fixation of organometallic fragments on a lanthanide oxide surface.
AB  - The reaction of the lanthanide trichloride hexahydrates [LnCl(3).6H(2)O] (Ln =
      Yb, Lu) with two equivalents of benzoylferrocenoylmethane resulted in the
      tetranuclear lanthanide hydroxo clusters [Ln(4)(mu(3)-OH)(4)(FcacacPh)(8)] (Ln =
      Yb (1), Lu (2); FcacacPh = benzoylferrocenoylmethanide). Compounds 1 and 2 are
      made up of a distorted tetranuclear lanthanide Ln(4)O(4) cubane core consisting
      of four mu(3)-oxygen atoms while the eight FcacacPh ligands build up the
      peripheral part of the cluster. These compounds contain the maximum number of
      ferrocene units anchored to any molecular metal-heteroatom framework reported so
      far and for which the X-ray structures are known.

PMID- 16429172
TI  - The relative stabilities of 11-vertex nido- and 12-vertex closo-heteroboranes and
      -borates: facile estimation by structural or connection increments.
AB  - The relative thermodynamic stabilities of ortho-, meta- and para-isomers of 12
      vertex closo-heteroboranes and -borates with different p-block heteroatoms were
      determined using density functional theory. More electronegative (smaller)
      heteroatoms tend to occupy non-adjacent, whereas less electronegative (larger)
      heteroatoms tend to occupy adjacent vertices in the thermodynamically most stable
      closo-diheterododecaborane isomers. The computed relative stabilities agree
      perfectly with experimental observations. The energy differences of para- and
      meta- relative to ortho-isomers of 12-vertex closo-heteroboranes generally depend
      on the extent of electron localization by a given heteroatom and show highly
      periodic trends, i.e. increase along the period and decrease down the group. The
      energy penalties for the HetHet structural feature (two heteroatoms adjacent to
      each other) for the 12-vertex closo-cluster are apparently significantly
      different from those for the 11-vertex nido-cluster. Reformulating two 11-vertex
      nido-structural features, i.e. Het(5k)(2) and HetHet, in terms of connection
      increments along with the additional structural feature HetHet(m) give the
      relative stabilities of various isomeric 11-vertex nido- as well as 12-vertex
      closo-heteroboranes and -borates, using one unique set of increments.

PMID- 16429171
TI  - cis-[PtBr2{PPh2(4-catechol)}2]: synthesis, crystal structure, and computational
      modelling of its binding to nanocrystalline TiO2.
AB  - The complex cis-[PtBr(2){PPh(2)(4-catechol)}(2)]1 has been synthesized by
      cleavage of the four methyl groups from cis-[PtCl(2){PPh(2)(4-veratrole)}(2)]
      using BBr(3), followed by work-up in the presence of excess bromide. An X-ray
      crystal structure of 1.(ethanol)(2) confirms that the two catechol rings are
      adjacent to each other and approximately parallel, and therefore well structured
      to act as double bidentate ligands for adjacent metal atoms on the surface of a
      nanocrystal. The crystal packing of 1.(ethanol)(2) involves intermolecular
      hydrogen-bonding interactions and a parallel fourfold phenyl embrace between
      PPh(2) moieties. Density functional calculations have demonstrated that
      conformational variability of the aryl rings in cis-[PtBr(2){PPh(2)(4
      catechol)}(2)] is energetically feasible, and two conformations of cis
      [PtBr(2){PPh(2)(4-catechol)}(2)] as a complex ligand for Ti atoms on the various
      surfaces of the anatase and rutile structures of TiO(2) have been assessed for
      geometrical commensurability. Three structural models for adsorbates of cis
      [PtBr(2){PPh(2)(4-catechol)}(2)] on TiO(2) are developed for anatase (110),
      anatase (101), and rutile (001).

PMID- 16429173
TI  - Metal complexes from 1,1'-di(pyrazinyl)ferrocene: coordination polymers and
      bridged diferrocenes.
AB  - Ferrocene-based ligands 1,1'-di(pyrazinyl)ferrocene (L1) and 1,1'-di(2
      pyrimidinyl)ferrocene (L2) were synthesized and copper and silver complexes were
      obtained from L1. Coordination polymers [{Cu(2)(PhCOO)(4)}(L1)](n) (1),
      [{Cu(2)(C(5)H(11)COO)(4)}(L1)](n) (2), and
      [{Cu(2)(OAc)(4)}(L1)](n).0.5n[Cu(2)(OAc)(4)(H(2)O)(2)].1.5nCH(3)CN (3) resulted
      from the reaction with the corresponding copper carboxylates. In all three
      complexes, L1 links the dinuclear copper carboxylate units to form one
      dimensional step-like chains. In 2, these chains are further linked by
      [Cu(2)(OAc)(4)(H(2)O)(2)] dinuclear units via hydrogen bonding to form sheet
      structures. The reaction of L1 with copper(I) iodide resulted in a multinuclear
      complex [(CuI)(4)(L1)(2)].(L1) (4), which contains a [(CuI)(4)(L1)(2)]
      diferrocene unit with a step-like (CuI)(4) core. Reactions of L1 with silver(I)
      salts resulted in silver-bridged diferrocenes [Ag(2)(L1)(2)]X(2) (X = ClO(4) (5a,
      b), NO(3) (6a-c) and PF(6) (7)), some of which incorporate aromatic solvents into
      their crystal lattices. The intramolecular Ag...Ag separations in these
      metallamacrocycles (3.211-3.430 A) depended upon the counter-anions and on the
      coordination mode of the silver ions. In all of these coordination complexes,
      L1adopts a synperiplanar eclipsed conformation and acts as a bidentate ligand,
      with only the 5-nitrogen of each pyrazine ring involved in coordination.

PMID- 16429174
TI  - Electrochemical properties of dinuclear [Ru([n]aneS4)] complexes of 2,3-bis(2
      pyridyl)pyrazine.
AB  - The syntheses of three new dinuclear [Ru([n]aneS(4))] complexes, where n = 12,
      14, 16, bridged by the ligand 2,3-bis(2-pyridyl)pyrazine, (dpp) are reported. The
      absorption spectra of the complexes show changes in the energy of the MLCT bands
      within the series, indicating that the thiacrown ligands stabilise the Ru(II)
      oxidation state to different degrees. Electrochemical studies are also consistent
      with these observations, and reveal that the pi-acceptor properties of [n]aneS(4)
      ligands lead to metal based oxidation couples occurring at potentials that are
      more anodic than those observed in the analogous dinuclear [Ru(bpy)(2)](2+)
      complex. Despite the back-bonding properties of the thiacrown ligands leading to
      a reduction in ligand-bridge mediated metal-metal coupling, electrochemical
      interactions between the metals are still considerable.

PMID- 16429175
TI  - Structural and coordination properties of 1,2-bis(cyclopropyl)-3,4-bis(2,4,6-tri
      tert-butylphenyl)-3,4-diphosphinidenecyclobutene prepared by dehydrogenative
      homocoupling of 3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphaallene.
AB  - According to a protocol for the synthesis of phosphaallenes we recently
      established, 3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphallene was
      obtained from (Z)-2-bromo-3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1
      phosphapropene. A novel bidentate ligand, 1,2-bis(cyclopropyl)-3,4-bis(2,4,6-tri
      tert-butylphenyl)-3,4-diphosphinidenecyclobutene, was prepared by oxidative
      homocoupling of 3-cyclopropyl-1-(2,4,6-tri-tert-butylphenyl)-1-phosphaallene in
      the presence of butyllithium, together with the generation of hydrogen gas. The
      1,2-bis(cyclopropyl)-3,4-diphosphinidenecyclobutene was allowed to react with
      (tht)AuCl (tht = tetrahydrothiophene) to afford the corresponding digold(I)
      complex of a six-membered metallacycle containing the P=C-C=P skeleton. The
      molecular structures of the 2-bromo-3-cyclopropyl-1-phosphapropene, 1,2
      bis(cyclopropyl)-3,4-diphosphinidenecyclobutene and the digold complex were
      unambiguously determined by X-ray crystallography and are discussed from the
      point of view of the cyclopropyl conjugation.

PMID- 16429176
TI  - Organoaluminium complexes with sterically demanding oximato ligands: does a bulky
      and rigid ligand backbone change the aggregation motif?
AB  - The four organoaluminium ketoximates [(2,4-dimethylpentane-3-one
      oximato)AlMe(2)](2) (1), (meso)-[(norcamphor oximato)AlMe(2)](2) (2), {[(R,R)
      camphor oximato]AlMe(2)}(3) (3) and {[(R,S)-fenchone oximato]AlMe(2)}(2) (4) have
      been prepared by the reactions of the corresponding oximes with
      trimethylaluminium. All compounds have been fully characterized by means of IR,
      mass and multi-nuclear NMR spectroscopy ((1)H, (13)C, (27)Al) and by elemental
      analyses. The crystal structures of three of these compounds (2, 3 and 4) were
      determined, revealing the aggregation motif of organometallic group 13 oximates
      to vary from the hitherto predominant six-membered dimeric M(2)N(2)O(2) array to
      others (six-membered M(3)O(3) core ring in the case of the camphor derivative;
      five-membered M(2)NO(2) core ring in the case of the fenchone derivative) so far
      only found e.g. in hydroxylamino complexes of group 13 metals. Furthermore,
      complexes 3 and 4 exhibit an unusual behaviour in solution, as indicated by
      upfield-shifted additional signals in their (27)Al NMR spectra, pointing at
      aluminium atoms in penta- or hexacoordination, respectively.

PMID- 16429177
TI  - The influence of ligand field effects on the magnetic exchange of high-spin
      Co(II)-semiquinonate complexes.
AB  - [Co(Me(4)cyclam)(tropolonate)](PF(6)) was synthesised and structurally
      characterised. Its electronic and W-band EPR spectra have been analysed by means
      of the angular overlap calculation of the Spin Hamiltonian parameters that
      provided also a satisfactory reproduction of the temperature dependence of the
      magnetic susceptibility. The present results can be interpreted assuming a pseudo
      octahedral character for the Co(II) center. This prompted us to reconsider the
      model formerly used for the analysis of the magnetic coupling between hs-Co(II)
      and the paramagnetic o-semiquinonate ligand in the corresponding derivatives
      [Co(Me(4)cyclam)(PhenSQ)](PF(6)) and [Co(Me(4)cyclam)(DTBSQ)](PF(6)). These
      results indicate that the effect of the magnetic coupling is active only below 50
      K and that a more refined model of exchange coupling between Co(II) and
      semiquinonato ligands is needed to quantitatively analyze the magnetic behaviour
      of this class of systems.

PMID- 16429178
TI  - Synthesis, structure and spectral and redox properties of new mixed ligand
      monomeric and dimeric Ru(II) complexes: predominant formation of the "cis-alpha"
      diastereoisomer and unusual 3MC emission by dimeric complexes.
AB  - The tetradentate ligands 1,8-bis(pyrid-2-yl)-3,6-dithiaoctane (pdto) and 1,8
      bis(benzimidazol-2-yl)-3,6-dithiaoctane (bbdo) form the complexes [Ru(pdto)(mu
      Cl)](2)(ClO(4))(2) 1 and [Ru(bbdo)(mu-Cl)](2)(ClO(4))(2) 2 respectively. The new
      di-mu-chloro dimers 1 and 2 undergo facile symmetrical bridge cleavage reactions
      with the diimine ligands 2,2'-bipyridine (bpy) and dipyridylamine (dpa) to form
      the six-coordinate complexes [Ru(pdto)(bpy)](ClO(4))(2) 3,
      [Ru(bbdo)(bpy)](ClO(4))(2) 4, [Ru(pdto)(dpa)](ClO(4))(2) 5 and
      [Ru(bbdo)(dpa)](ClO(4))(2) 6 and with the triimine ligand 2,2':6,2''-terpyridine
      (terpy) to form the unusual seven-coordinate complexes
      [Ru(pdto)(terpy)](ClO(4))(2) 7 and [Ru(bbdo)(terpy)](ClO(4))(2) 8. In 1 the
      dimeric cation [Ru(pdto)(mu-Cl)](2)(2+) is made up of two approximately
      octahedrally coordinated Ru(II) centers bridged by two chloride ions, which
      constitute a common edge between the two Ru(II) octahedra. Each ruthenium is
      coordinated also to two pyridine nitrogen and two thioether sulfur atoms of the
      tetradentate ligand. The ligand pdto is folded around Ru(II) as a result of the
      cis-dichloro coordination, which corresponds to a "cis-alpha" configuration
      [DeltaDelta/LambdaLambda(rac) diastereoisomer] supporting the possibility of some
      attractive pi-stacking interactions between the parallel py rings at each
      ruthenium atom. The ruthenium atom in the complex cations 3a and 4 exhibit a
      distorted octahedral coordination geometry composed of two nitrogen atoms of the
      bpy and the two thioether sulfur and two py/bzim nitrogen atoms of the pdto/bbdo
      ligand, which is actually folded around Ru(II) to give a "cis-alpha" isomer. The
      molecule of complex 5 contains a six-coordinated ruthenium atom chelated by pdto
      and dpa ligands in the expected distorted octahedral fashion. The (1)H and (13)C
      NMR spectral data of the complexes throw light on the nature of metal-ligand
      bonding and the conformations of the chelate rings, which indicates that the
      dithioether ligands maintain their tendency to fold themselves even in solution.
      The bis-mu-chloro dimers 1 and 2 show a spin-allowed but Laporte-forbidden
      t(2g)(6)((1)A(1g))--> t(2g)(5) e(g)(1)((1)T(1g), (1)T(2g)) d-d transition. They
      also display an intense Ru(II) dpi--> py/bzim (pi*) metal-to-ligand charge
      transfer (MLCT) transition. The mononuclear complexes 3-8 exhibit dpi-->pi* MLCT
      transitions in the range 340-450 nm. The binuclear complexes 1 and 2 exhibit a
      ligand field ((3)MC) luminescence even at room temperature, whereas the
      mononuclear complexes 3 and 4 show a ligand based radical anion ((3)MLCT)
      luminescence. The binuclear complexes 1 and 2 undergo two successive oxidation
      processes corresponding to successive Ru(II)/Ru(III) couples, affording a stable
      mixed-valence Ru(II)Ru(III) state (K(c): 1, 3.97 x 10(6); 2, 1.10 x 10(6)). The
      mononuclear complexes 3-7 exhibit only one while 8 shows two quasi-reversible
      metal-based oxidative processes. The coordinated 'soft' thioether raises the
      redox potentials significantly by stabilising the 'soft' Ru(II) oxidation state.
      One or two ligand-based reduction processes were also observed for the
      mononuclear complexes.

PMID- 16429179
TI  - New discrete metallocycles incorporating palladium(II) and platinum(II) corners
      and dipyridyldibenzotetraaza[14]annulene side units.
AB  - The interaction of the extended, fully-conjugated macrocycle,
      dipyridyldibenzotetraaza[14]annulene (1), with the square planar palladium(II)
      and platinum(II) complexes [M(dppp)(triflate)(2)].2H(2)O (M = Pd, Pt) has been
      investigated in both solution and the solid state. In each case solid products
      showing a 1:1 ratio of metal complex: 1 were obtained. A 1:1 mixture of and
      [Pd(dppp)(2)(triflate)(2)].2H(2)O in dichloromethane yielded two major products
      as evidenced by the presence of two singlets in the (31)P {(1)H}-NMR spectrum of
      the reaction solution. Similarly, two singlets were evident in the corresponding
      spectrum obtained on dissolving the 1:1 product in nitrobenzene. The temperature
      and concentration dependence of the spectra clearly showed that the two species
      present in each case were in equilibrium. From the temperature dependence, the
      low field signal was assigned to the smaller of the two species. Broadly parallel
      behaviour was observed for the corresponding platinum-containing system. The MS
      ESI spectrum of the platinum derivative showed the presence of a dinuclear
      species corresponding to [Pt(dppp)(1)](2)(2+) and an X-ray structure of this
      product confirmed that a corresponding dinuclear complex exists in the solid
      state. This product has a geometry in which two curved macrocyclic side units
      bridge two metal centres to yield an ellipse-shaped structure. Attempts to employ
      pulsed-field gradient spin-echo (PGSE) (31)P NMR confirmed that the lower-field
      resonance corresponded to the smaller of the two species in solution. STM (HOPG)
      imaging of the palladium- and platinum-containing products revealed arrays that
      appear to be composed of "zipper-like" rows of dimer units, with the dimensions
      of the latter comparing well with those found in the X-ray structure of
      [Pt(dppp)(1)](2)(2+).

PMID- 16429181
TI  - Influence of cervical preflaring on determination of apical file size in
      maxillary molars: SEM analysis.
AB  - The purpose of this study was to investigate the influence of cervical preflaring
      on determination of the initial apical file in mesiobuccal roots of maxillary
      molars. Fifty first molars with degree of curvature of the mesiobuccal root
      between 10 degrees and 15 degrees were utilized. After standard access opening
      and removal of pulp tissue, the working length (WL) was determined at 1 mm from
      the root apex. Five groups (n=10) were formed at random, according to the type of
      cervical preflaring performed. In group 1, the size of the initial apical file
      was determined without cervical preflaring. In groups 2 to 5, the cervical and
      middle thirds of the canals were preflared with Gates-Glidden drills, K3 Orifice
      Opener instruments, ProTaper instruments and LA Axxess burs, respectively. Canals
      were sized manually with K-files, starting with size 08 K-files, inserted
      passively up to the WL. File sizes were increased until a binding sensation was
      felt at the WL and the size of the file was recorded. The binding instruments
      were fixed into the canals at the WL with methylcyanacrylate. Cross-sections of
      the WL region were examined under scanning electron microscopy and the
      discrepancies between the canal diameter and the diameter of first file to bind
      at the WL were calculated using UTHSCSA ImageTool software. Data were analyzed
      statistically by ANOVA and multiple comparisons were done by Tukey's HSD post-hoc
      test. Significant differences (p<0.001) were found among the groups. The major
      discrepancy was observed for the group without preflaring (mean 0.1543 mm +/-
      0.0216). Cervical preflaring with LA Axxess burs produced the least discrepancies
      between the canal size and the diameter of the initial apical instrument (mean
      0.026 mm +/- 0.0037), followed by ProTaper files (mean 0.0567 mm +/- 0.0354).
      Canals preflared with Gates-Glidden drills and K3 Orifice Opener instruments
      showed statistically similar discrepancy results to each other (p>0.05) (means
      0.1167 mm +/- 0.0231 and 0.1313 mm +/- 0.0344, respectively). In conclusion,
      preflaring of the cervical and middle thirds improved the determination of the
      initial apical instrument. Canals preflared with LA Axxess burs showed a more
      accurate binding of the files to the anatomical diameter at the WL in the
      mesiobuccal roots of maxillary first molars.

PMID- 16429180
TI  - In vitro evaluation of the susceptibility of endodontic pathogens to calcium
      hydroxide combined with different vehicles.
AB  - The aim of this study was to investigate in vitro the antimicrobial activity of
      calcium hydroxide [Ca(OH)2] in combination with different vehicles against
      endodontic pathogens. For such purpose, a broth dilution test was performed.
      Pastes were prepared with Ca(OH)2 powder and the following vehicles: sterile
      water, glycerin, camphorated monochlorophenol (CMCP), CMCP + glycerin,
      polyethyleneglycol and CMCP + polyethyleneglycol. The time required for the
      pastes to produce negative cultures against the tested microorganisms was
      recorded and analyzed statistically using the Kruskal Wallis test at 5%
      significance level. Timing for pastes to eliminate the aerobic and facultative
      anaerobic microorganisms ranged from 6 to 24 h, while strict anaerobic
      microorganisms were inhibited within 30 s to 5 min. Microbial susceptibility,
      ranked from weakest to strongest, can be presented as follows: Enterococcus
      faecalis (the most resistant microorganism), Candida albicans, Staphylococcus
      aureus, Porphyromonas gingivalis, Porphyromonas endodontalis and Prevotella
      intermedia (the last two microorganisms required the same time to be eliminated).
      In conclusion, calcium hydroxide pastes needed more time to eliminate facultative
      than anaerobic microorganisms. These findings suggest that the antimicrobial
      property is related both to paste formulation and to microbial susceptibility.

PMID- 16429182
TI  - In vitro evaluation of apical sealing in root apex treated with demineralization
      agents and retrofiled with mineral trioxide aggregate through marginal dye
      leakage.
AB  - The purpose of this study was to evaluate the apical seal in root apex treated
      with different demineralization agents and retrofilled with mineral trioxide
      aggregate (MTA) using marginal dye leakage. Fifty-six, human single-rooted teeth
      were instrumented, filled, resected and had retrofilling cavities prepared with
      ultrasonic tips. Demineralizing agents were applied before the apical cavities
      were retrofilled with Pro Root MTA. The specimens were assigned to 4 groups
      (n=14), as follows: group 1 (no demineralizing agent); group 2 (35% phosphoric
      acid, for 15 s); group 3 (17% EDTA solution, pH 7, for 3 min); and group 4 (24%
      EDTA gel, pH 7, for 4 min). The extension of dye (2% rhodamine B, at 37 degrees
      C, for 24 h) penetration was measured in millimeters using a stereomicroscope.
      Results were statistically analyzed by ANOVA and Tukey's test at 5% significance
      level. Among the experimental groups, the least extension of dye penetration was
      observed in group 1 (1.89 mm), followed by groups 2 (2.18 mm), 4 (2.54 mm) and 3
      (2.64 mm). No statistically significant differences (p<0.05) were found in
      marginal microleakage among groups 1, 2 and 4 and groups 2, 3 and 4. Based on the
      results obtained in this study, it may be concluded that the application of
      demineralizing agents cannot be recommended when MTA is used in periradicular
      surgeries.

PMID- 16429183
TI  - Antimicrobial activity of Arctium lappa constituents against microorganisms
      commonly found in endodontic infections.
AB  - This study evaluated in vitro the antimicrobial activity of rough extracts from
      leaves of Arctium lappa and their phases. The following microorganisms, commonly
      found in the oral cavity, specifically in endodontic infections, were used:
      Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus
      subtilis and Candida albicans. The agar-diffusion method allowed detection of the
      hexanic phase as an inhibitor of microbial growth. Bioautographic assays
      identified antimicrobial substances in the extract. The results showed the
      existence, in the rough hexanic phase and in its fractions, of constituents that
      have retention factors (Rf) in three distinct zones, thereby suggesting the
      presence of active constituents with chemical structures of different polarities
      that exhibited specificity against the target microorganisms. It may be concluded
      that the Arctium lappa constituents exhibited a great microbial inhibition
      potential against the tested endodontic pathogens.

PMID- 16429184
TI  - Influence of the remaining coronal structure on the resistance of teeth with
      intraradicular retainer.
AB  - The aim of this study was to compare the resistance of endodontically treated
      teeth with intraradicular retainer different amounts of remaining coronal
      structure. Fifty freshly extracted maxillary canines were endodontically treated
      and randomly assigned to five groups (n=10), as follows: group 1 (control) =
      teeth with custom cast post and core; group 2 = teeth without remaining coronal
      structure; group 3, 4 and 5 = teeth with 1 mm, 2 mm and 3 mm of remaining coronal
      structure, respectively. All specimens in groups 2 to 5 were restored with
      prefabricated post and resin core. The teeth were embedded in acrylic resin and
      the fracture strength was measured on a universal testing machine at 45 degrees
      to the long axis of the tooth until failure. Data were analyzed statistically by
      one-way analysis of variance and Tukey's test. There was no significant
      differences (p>0.05) between the control group and group 2, and between groups 3,
      4 and 5 (p>0.05). Control group and group 2 had significantly higher resistance
      strength than groups 3, 4 and 5 (p<0.00001). The findings of this study showed
      that teeth without remaining coronal structure had significantly higher fracture
      strength than those with remaining coronal structure (1 mm, 2 mm and 3 mm). When
      the dental crown was not completely removed, the amount of remaining coronal
      dentin did not significantly affect the fracture strength of endodontically
      treated teeth with intraradicular retainer.

PMID- 16429185
TI  - Shear bond strength of dental porcelains to nickel-chromium alloys.
AB  - The continuous technological advance and increasing availability of new base
      metal alloys and ceramic systems in the market, coupled to the demands of daily
      clinical practice, have made the constant evaluation of the bond strength of
      metal/porcelain combinations necessary. This study evaluated the metal/porcelain
      shear bond strength of three ceramic systems (Duceram, Williams and Noritake) in
      combination with three nickel-chromium (Ni-Cr) alloys (Durabond, Verabond and
      Viron). Thirty cast cylinder specimens (15 mm high; 6 mm in diameter) were
      obtained for each alloy, in a way that 10 specimens of each alloy were tested
      with each porcelain. Bond strength was measured with an Emic screw-driven
      mechanical testing machine by applying parallel shear forces to the specimens
      until fracture. Shear strength was calculated using the ratio of the force
      applied to a demarcated area of the opaque layer. Mann-Whitney U test was used
      for statistical analysis of the alloy/ceramic combinations (p<0.05).
      Viron/Noritake had the highest shear bond sregnth means (32.93 MPa), while
      Verabond/Duceram (16.31 MPa) presented the lowest means. Viron/Noritake differed
      statistically from other combinations (p<0.05). Viron/Duceram had statistically
      significant higher bond strengths than Verabond/Duceram, Verabond/Williams and
      Durabond/Noritake (p<0.05). It was also found significant difference (p<0.05)
      between Verabond/Noritake, Verabond/Duceram and Durabond/Noritake. No
      statistically significant difference (p>0.05) were observed among the other
      combinations. In conclusion, the Noritake ceramic system used together with Viron
      alloy presented the highest resistance to shear forces, while Duceram bonded to
      Verabond presented the lowest bond strength. Viron/Duceram and Verabond/Noritake
      provided intermediate results. The combinations between the Williams ceramic
      system and Ni-Cr alloys had similar shear strengths among each other.

PMID- 16429187
TI  - In vitro evaluation of the retention of zirconia-based ceramic posts luted with
      glass ionomer and resin cements.
AB  - The retention of zirconia-based ceramic posts (CosmoPost system) luted with glass
      ionomer and resin cements was evaluated. Thirty-two extracted, caries-free,
      unrestored teeth were selected and stored in chlorhexidine and water solution.
      The teeth were endodontically treated and randomly assigned to two groups (n=16).
      Each tooth was decoronated and prepared to a depth of 10.0 mm from root surface
      to receive a 1.4 mm diameter zirconium dioxide post. Each group had posts
      cemented with either glass ionomer cement (Fuji I) or resin cement (Variolink
      II). The post/teeth specimens were embedded in resin blocks and subjected to
      tensile testing. The tensile force required to dislodge the cemented posts in a
      tensile testing machine was recorded. The mean stress values of both groups were
      analyzed for statistical differences using ANOVA and Student's t-test.
      Significance level was set at 5%. Mean peak forces at failure (N) and standard
      deviation for the tested cements were the following: Fuji I = 121.8 (+/-17.4) and
      Variolink II = 228.1 (+/-36.8). Posts luted with the resin cement presented
      statistically significant higher tensile bond strength than those retained with
      glass ionomer (p<0.05). It may be concluded that zirconia posts cemented with
      resin-based cement (Variolink II) failed at statistically significant higher
      values compared to those cemented with glass ionomer cement (Fuji I). Regardless
      of the cement type, the posts failed adhesively at the cement/post interface when
      subjected to a tensile force.

PMID- 16429186
TI  - Evaluation of digital optical density of bone repair in rats medicated with
      ketoprofen.
AB  - The purpose of this study was to evaluate the influence of ketoprofen on bone
      repair process in tibiae of rats by means of analysis of the digital optical
      density. Twenty Wistar rats were assigned to two groups: an untreated control
      group and a group treated with ketoprofen. The experimental procedures comprised
      the following stages: general anesthesia, preparation of a unicortical bone
      defect on the left tibia of each rat, medication with ketoprofen and radiographic
      examination. Digital radiographic images were acquired using Visualix GX-S-HDI
      digital sensor and an x-ray equipment. Radiographs were taken at baseline, 7, 14,
      21 and 30 days postoperatively and the optical density (OD) was evaluated using
      the Vix win 1.4 system. The mean values of OD readings were analyzed
      statistically by ANOVA and Tukey's test with significance level set at a=5%. The
      control group showed a statistically significant correlation (p=0.001) between
      time and optical density, while the ketoprofen group exhibited a weak and not
      statistically significant correlation (p=0.100). The control group presented the
      smallest OD ratios at days 1 and 7, and the greatest OD ratios at days 14, 21 and
      30, with statistically significant difference (p=0.001). There was no significant
      differences (p=0.100) among the OD ratios in the ketoprofen group, regardless of
      the evaluation period. The findings of this study suggest that ketoprofen
      influenced bone repair process because there was an increase in optical density
      during the first week and delayed new bone formation after the 21st day.

PMID- 16429188
TI  - Effect of the increase of energy density on Knoop hardness of dental composites
      light-cured by conventional QTH, LED and xenon plasma arc.
AB  - The aim of this study was to evaluate the effect of the increase of energy
      density on Knoop hardness of Z250 and Esthet-X composite resins. Cylindrical
      cavities (3 mm in diameter X 3 mm in depth) were prepared on the buccal surface
      of 144 bovine incisors. The composite resins were bulk-inserted and polymerized
      using different light-curing units and times: conventional QTH (quartz-tungsten
      halogen; 700 mW/cm(2); 20 s, 30 s and 40 s); LED (light-emitting diode; 440
      mW/cm(2); 20 s, 30 s and 40 s); PAC (xenon plasma arc; 1700 mW/cm(2); 3 s, 4.5 s
      and 6 s). The specimens were stored at 37 degrees C for 24 h prior to sectioning
      for Knoop hardness assessment. Three measurements were obtained for each depth:
      top surface, 1 mm and 2 mm. Data were analyzed statistically by ANOVA and Tukey's
      test (p<0.05). Regardless of the light source or energy density, Knoop hardness
      of Z250 was statistically significant higher than that of Esthet-X (p<0.05).
      Specimens cured with PAC had lower hardness than those cured with QTH and LED
      (p<0.05). Higher Knoop hardness was obtained when the energy density was
      increased for LED and PAC (p<0.05). No statistically significant differences
      (p>0.05) were found for QTH. Knoop hardness values decreased with the increase of
      depth. The increase of energy density produced composites with higher Knoop
      hardness means using LED and PAC.

PMID- 16429189
TI  - Development of the osteoblast phenotype of serial cell subcultures from human
      bone marrow.
AB  - Bone marrow cells have been used for testing biocompatibility of bone substitute
      materials that would be applied in maxillofacial and orthopedic surgeries.
      However, it remains unclear whether cells in serial subcultures retain the
      ability to differentiate into osteoblasts. The purpose of this study was to
      compare the development of osteoblast phenotype of serially passaged cells from
      human bone marrow. Cells from first to third passage were cultured (2 x 10(4)
      cells/well) in supplemented culture medium. Cells were incubated at 37 degrees C
      in a humidified atmosphere of 5% CO2 and 95% air. Cell attachment was assessed at
      4 and 24 h. At 7, 14 and 21 days, cell proliferation, cell viability, total
      protein content and alkaline phosphatase (ALP) activity were evaluated. Bone-like
      formation was evaluated at 14 and 21 days. Data were compared by two-way ANOVA
      and Duncan's multiple range test. Cell attachment, cell viability and total
      protein content were not affected by serial subcultures. However, serial
      subcultures did interfered negatively with osteoblast differentiation as shown by
      osteoblast parameters observed in second and third subcultures, such as
      continuous cell proliferation, lower ALP activity and bone-like formation in
      comparison to first subculture. Therefore, it is important to evaluate cell
      ability to growth and differentiate before selecting the cell population for
      studies that investigate the biocompatibility of materials to replace bone
      tissue.

PMID- 16429190
TI  - Analysis of MMP-9 and TIMP-2 gene promoter polymorphisms in individuals with
      hypodontia.
AB  - Hypodontia, the congenital absence of one or a few teeth, is one of the most
      common developmental alterations of human dentition. It may cause masticatory and
      speech dysfunctions and create esthetic problems with orthodontic and prosthetic
      implications. MMP-9 is an important member of the matrix metalloproteinase (MMP)
      family that participates in remodeling of extracellular matrix during tooth
      development. A C-to-T base exchange at position -1562 creates two different
      alleles, and the CT and TT genotypes promote high activity of the MMP-9 gene
      promoter. Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates the activity
      of MMPs in the extracellular matrix and is co-expressed with gelatinases A (MMP
      2) and B (MMP-9) during mouse tooth morphogenesis. A polymorphism in the TIMP-2
      gene promoter at position -418 has been found in a Sp-1 binding site. In this
      study, the association between these DNA polymorphisms and hypodontia has been
      investigated. The significance of differences in frequencies of polymorphisms in
      control and test groups was assessed by Chi-square test (p<0.05). Data suggested
      that MMP-9 gene promoter polymorphism was not associated with hypodontia. The
      high frequency of GG genotype in the TIMP-2 gene promoter showed that this site
      was unsuitable for studies of DNA polymorphism-disease associations in the
      studied population.

PMID- 16429191
TI  - Electromyographic analysis of the orbicularis oris muscle in oralized deaf
      individuals.
AB  - Electromyography has been used to evaluate the performance of the peribuccal
      musculature in mastication, swallowing and speech, and is an important tool for
      analysis of physiopathological changes affecting this musculature. Many
      investigations have been conducted in patients with auditory and speech
      deficiencies, but none has evaluated the musculature responsible for the speech.
      This study compared the electromyographic measurements of the superior and
      inferior fascicles of the orbicularis oris muscle in patients with profound
      bilateral neurosensorial hearing deficiency (deafness) and healthy volunteers.
      Electromyographic analysis was performed on recordings from 20 volunteers (mean
      age of 18.5 years) matched for gender and age. Subjects were assigned to two
      groups, as follows: a group formed by 10 individuals with profound bilateral
      neurosensorial hearing deficiency (deaf individuals) and a second group formed by
      10 healthy individuals (hearers). Five clinical conditions were evaluated:
      suction, blowing, lip projection and compression, and production of the syllable
      "Pa". It was found that the deaf patients presented muscle hyperactivity in all
      clinical conditions, and that the inferior fascicle of the orbicularis oris
      muscle showed higher electromyographic activity rates, suggesting the need for a
      hearing-speech treatment with emphasis on oral motricity.

PMID- 16429192
TI  - Evaluation of the etiology of ocular globe atrophy or loss.
AB  - This survey investigated the etiology of atrophy or loss of the ocular globe in
      patients assisted at the Maxillofacial Prosthetics Clinic of two Schools of
      Dentistry in Sao Paulo State, Brazil. A total of 238 patients were examined and
      their clinical files were reviewed. The etiology of eyeball atrophy/loss was
      assessed with respect to gender, age group, affected side and type ophthalmologic
      surgery performed. The greatest incidence of ocular globe loss was due to
      traumatic etiology (57.14%), followed by pathogenic (36.13%) and congenital
      (5.04%) etiologies. Comparing the genders, a predominance of male patients was
      observed (61.76%; p<0.01). The age group most frequently affected was between 21
      and 40 years (42.01%; p<0.01). For all types of etiologies investigated in this
      study, enucleation was the most commonly used surgical procedure for removal of
      the ocular globe (66.38%; p<0.01). Loss of the left eye was predominantly seen
      (55.04%), even though no statistically significant difference was found between
      sides (p>0.01).

PMID- 16429193
TI  - Clinical, radiographic, biochemical and histological findings of florid cemento
      osseous dysplasia and report of a case.
AB  - Florid cemento-osseous dysplasia has been described as a condition that
      characteristically affects the jaws of middle-aged black women. It usually
      manifests as multiple radiopaque cementum-like masses distributed throughout the
      jaws. This condition has also been classified as gigantiform cementoma, chronic
      sclerosing osteomyelitis, sclerosing osteitis, multiple estenosis and sclerotic
      cemental masses. The authors present a case of an uncomplicated florid cemento
      osseous dysplasia in a 48-year-old black woman. Multiple sclerotic masses with
      radiolucent border in the mandible were identified radiographically.
      Histopathologic findings revealed formation of calcified dense sclerotic masses
      similar to cementum. All clinical, radiographic, biochemical and histological
      features were suggestive of the diagnosis of florid cemento-osseous dysplasia.

PMID- 16429194
TI  - Adenomatoid odontogenic tumor--a rare cause of jaw swelling.
AB  - Adenomatoid odontogenic tumor (AOT) is an uncommon tumor of odontogenic origin,
      characterized histologically by the formation of ductlike structures with amyloid
      like deposits. Histogenesis of AOT is still uncertain and it is often considered
      as a hamartomatous lesion rather than a true neoplasm. AOT has a benign behavior
      and conservative surgical enucleation or curettage is sufficient. We report a
      case of AOT in a 15-year-old female who presented with left-sided jaw swelling
      with tooth resorption. Histopathology revealed intraosseus follicular variant of
      AOT. A brief review of literature is also discussed.

PMID- 16429195
TI  - Periapical cyst repair after nonsurgical endodontic therapy--case report.
AB  - This article presents the procedures that must be considered for periapical cyst
      repair after nonsurgical endodontic treatment. The case of a periapical cyst
      associated to the left maxillary lateral incisor is reported. Nonsurgical root
      canal therapy was performed and lesion healing was confirmed radiographically
      after 24 months. Differential diagnosis, endodontic infection control, apical
      foramen enlargement and filling of the cystic cavity with a calcium hydroxide
      paste were important procedures for case resolution.

PMID- 16429196
TI  - [The sugarcane juice was delicious, but...].

PMID- 16429197
TI  - [Cardiology in the 21st. Century. Is PDA an indispensable tool for the
      practice?].

PMID- 16429198
TI  - [Thirty years of postgraduation in cardiology].

PMID- 16429199
TI  - [Assessing autonomic function in hypertrophic cardiomyopathy].
AB  - OBJECTIVE: Assess the autonomic function in hypertrophic cardiomyopathy (HCM)
      through heart rate variability (HRV) and to correlate it to echocardiographic
      data. METHODS: Two groups were studied, and compared for gender, age and HR: A)
      Ten (10) patients reporting septal HCM (70% non-obstructive); B) Ten (10) healthy
      volunteers. HRV was analyzed along four successive stages: at rest, under
      controlled breathing, while bending, and controlled breathing associated to
      bending. Variables means were compared between groups and intra-groups in the
      different stages; in Group A, variables means were correlated to
      echocardiographic measurements (interventricular septum and left atrial
      diameter). RESULTS: No HRV difference was reported among groups in the first 3
      stages. In the fourth stage vagal activity was shown to be higher in Group A
      [quadratic mean log between RR intervals (RMSSD) - 1.35+/-0.14 vs 1.17+/-0.16;
      p=0.019; high frequency component logarithm (LogHF)- 4.89+/-0.22 vs 4.62+/-0.26;
      p=0.032]. Along the stages, vagal measurements [rate of pairs of consecutive RR
      intervals whose difference is > or =50 ms (pNN50) and LogHF] also showed lower
      reduction in the third stage in Group A, while LogHF showed some increase in last
      stage (p=0.027), thus indicating marked parasympathetic activity in that group.
      Group A HRV analysis showed no difference among patients reporting larger
      hypertrophy or atrial diameter. CONCLUSION: 1) Parasympathetic prevalence was
      shown during autonomic stimulation in HCM patients; 2) No correlation was found
      between HRV and echocardiographic measurements under analysis.

PMID- 16429200
TI  - [Myocardial viability in a single-vessel disease: the role of a dobutamine stress
      echocardiography].
AB  - OBJECTIVE: To investigate a group of patients that have a significant lesion in a
      single-vessel and to demonstrate whether or not the sensitivity and specificity
      of a dobutamine stress echocardiography (DSE) was valuable in the evaluation of
      myocardial viability for these patients. METHODS: Twenty patients who had
      undergone percutaneous transluminal coronary angioplasty (PTCA) were studied.
      This group was evaluated 2 to 7 days (3.65 +/- 1.69) before the procedure and 2
      to 5 days (4 +/- 0.80) after the procedure with a DSE. Myocardial viability was
      assessed three months after the procedure using a two dimensional echocardiogram.
      Twelve patients underwent PTCA on the left anterior descending artery (LAD), 7 on
      the right coronary artery (RC) and 1 on the circumflex artery (CX). Only one
      right coronary artery procedure was not 100% successful. RESULTS: From the 340
      segments that were studied, 99 (29.18%) demonstrated contractile alterations of
      which 63 were hypokinetic (63.4%), 28 akinetic (28.28%) and 8 dyskinetic (8.08%).
      In reference to the segments involved, we obtained a sensitivity of 92.59%,
      specificity of 84.45%, and accuracy of 88.88% for the DSE. The solitary case of
      PTCA for the circumflex artery demonstrated 100% sensitivity. The LAD
      demonstrated a sensitivity of 88.58%, specificity of 95% and accuracy of 90.91%.
      For the RC segments, sensitivity was 91.30%, specificity 83.33% and accuracy
      88.71%. All dyskinetic segments were unviable. The DSE predicted a 91.48%
      recovery rate for the 63 hypokinetic segments. CONCLUSION: The DSE is an
      effective test for evaluating myocardial viability in patients with a significant
      single-vessel disease.

PMID- 16429201
TI  - [Late heart evaluation of children with rheumatic mitral regurgitation submitted
      to reconstructive surgery with implantation of Gregori's ring].
AB  - OBJECTIVE: Assess late cardiological evolution of children with rheumatic mitral
      regurgitation (RMR) who underwent mitral valve reconstructive surgery with
      implantation of Gregori's ring (MVR), from 1987 to 2003. METHODS: A study was
      conducted to analyze a series of cases of 43 children with RMR who underwent MVR
      with ages ranged from five to twelve years (mean age 9.7 +/- 2.2 years); 25 of
      the patients were females (58.1%). Patients were evaluated as per the following
      clinical parameters: functional class of heart failure, heart auscultation,
      electrocardiogram, chest X-ray and echocardiographic findings. RESULTS: Forty
      three patients underwent preoperative evaluation during the postoperative period,
      the number of patients evaluated decreased to 31 due to the fact that 6 patients
      had died and 6 others underwent valve replacement surgery. Follow-up was carried
      out for 100% of the patients. A significant reduction of heart failure functional
      class was observed. Mitral systolic murmur became less intense during the
      postoperative period. The cardiac area on chest X-ray and the presence of left
      ventricular overload on electrocardiogram were reduced, as well as the mitral
      regurgitation level on echocardiographic study. After 188 months, the survival
      rate was 82%, and the annual mortality rate, 0.38%. Thirty-one (72.6%) patients
      did not require reoperation and the annual rate of patients who required further
      surgery was 0.51%. CONCLUSION: MVR is an effective procedure for treating RMR in
      children, resulting in a significant improvement of functional class, mitral
      systolic murmur and level of mitral regurgitation, as shown on Doppler
      echocardiogram.

PMID- 16429203
TI  - [Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency].
AB  - The objective of this article is to relate the diagnostic and clinical evolution
      of a 15 year old patient with a congenital adrenal steroidogenesis dysfunction
      that can present as hypertension diagnosed later in life (adolescence),
      virilization or salt wasting (birth and childhood).

PMID- 16429202
TI  - [Combined carotid endarterectomy and coronary artery bypass grafting. Analysis of
      the results].
AB  - OBJECTIVE: To evaluate the results of combined surgery (carotid endarterectomy
      and coronary artery bypass grafting) in patients with concomitant carotid and
      coronary artery disease. METHODS: The authors reviewed 49 different reports
      describing several aspects of the combined surgery in 4788 patients to analyze
      early events in the perioperative period. RESULTS: Overall stroke, acute
      myocardial infarction (AMI), and mortality rates were 4.3%, 2.2%, and 4.2%,
      respectively. Most recent papers (1990 to 2000) show significant lower incidence
      of strokes compared to those published earlier (1972 to 1989) (4.1% x 10.2%; p <
      0.05). In this same survey, the incidence of postoperative stroke was higher in
      the series with a small sample (n < 50) than in those with a larger population (n
      > 100) (7.2% x 3.9%; p < 0.05), denoting the impact of surgeons' experience on
      postoperative results. CONCLUSION: In sum, we believe that combined carotid
      endarterectomy and coronary artery bypass grafting is a safe and effective
      procedure when performed by experienced and qualified surgeons.

PMID- 16429204
TI  - [Restrictive cardiomyopathy due to myocardial cysticercosis].
AB  - There is no description of cysticercosis affecting heart function. In the present
      report, the authors describe the case of a 46-year-old woman with cardiac
      cysticercosis and heart failure, presenting with echocardiographic findings
      suggestive of restrictive cardiomyopathy and myocardial microcalcifications
      suggestive of cardiac infiltration by the disease.

PMID- 16429205
TI  - [Some comments on the inverted pyramid of medical qualification in Brazil and how
      it affects training in cardiology].

PMID- 16429206
TI  - [Renal disease as a cardiovascular risk factor].

PMID- 16429207
TI  - [Case 06/2005--progressive heart failure in a 65 year-old man with permanent
      cardiac pacemaker].

PMID- 16429208
TI  - [Case 03/2005--26-year-old male with partial atrioventricular septal defect with
      moderate pulmonary stenosis].

PMID- 16429209
TI  - Failure to thrive: still a problem of definition.
AB  - The term 'failure to thrive' (FTT) is widely used to describe inadequate growth
      in early childhood. However, no consensus exists concerning the specific
      anthropometrical criteria to define this description. The aim of this study was
      to make an updated assessment concerning the use of FTT definitions and describe
      possible trends regarding the use of specific criteria. A cross-sectional review
      was done covering English-language articles published from January 2003 until
      June 2004, and recent textbooks of general pediatrics. Most of the reviewed
      literature broadly defined FTT as inadequate growth and total agreement existed
      to define FTT based solely on anthropometrical parameters. Large differences,
      however, were seen regarding which growth parameters to use and whether to use
      attained values or velocities. Weight was the most predominant choice, but many
      included more than one anthropometrical parameter. Failure to thrive in children
      is currently described solely based on anthropometrical indicators, with weight
      gain as the predominant choice of indicator and cut off around the 5th
      percentile. Discussion is needed as to whether the term 'failure to thrive' is
      still a useful common term for pediatric undernutrition of different types.

PMID- 16429210
TI  - Gastroesophageal reflux disorder: a review for primary care providers.

PMID- 16429211
TI  - Recurrent pneumonia in children: a case report and approach to diagnosis.

PMID- 16429212
TI  - Gaps in pediatricians' advice to parents regarding early childhood aggression.
AB  - Persistent early childhood aggression is a strong predictor of violence later in
      life. To determine how well general pediatricians counsel parents regarding
      aggression management strategies, responses to open-ended questions and
      endorsements of specific aggression management strategies, among 27 pediatricians
      were evaluated. Sixteen (59%) screened regularly for aggression and 23 (85%)
      counseled (rather than referred) if there were parental concerns. Pediatricians
      were most likely to spontaneously recommend time-outs (85%) and verbal reprimands
      (78%) and much less likely to recommend other strategies such as redirecting
      (26%, p < 0.01) and promoting empathy (22%, p < 0.001). Pediatricians did endorse
      other aggression management strategies, however, when specifically asked about
      them. Pediatricians appear to take a limited approach to counseling parents of
      children with hurtful behavior. To increase health care providers' role in
      violence prevention, more systematic efforts are needed to increase rates of
      screening for early childhood aggression and to broaden the scope of how
      pediatricians counsel parents.

PMID- 16429213
TI  - Decreased regurgitation with a soy formula containing added soy fiber.
AB  - The objective of this randomized study was to determine if fiber-supplemented soy
      formula reduced regurgitation in young infants. We compared regurgitation in 179
      infants randomly assigned cow's milk-based (CM, 90) formula or soy formula with
      fiber (SF, 89). Initial daily incidence was similar (CM, 3.6; SF, 3.9 episodes),
      but significantly lower after 7 days on SF (CM, 3.4; SF, 2.3; p = 0.001). Less
      frequent regurgitation after 7 days on SF was sustained after 28 days (CM, 48%;
      SF, 31% of feedings; p = 0.001). Feeding SF effectively managed regurgitation
      while providing balanced nutrition without altering caloric distribution as
      occurs with adding rice cereal to formula.

PMID- 16429214
TI  - Nutrient deficiencies in tube-fed children.
AB  - The charts of children with gastrostomy or jejunostomy tubes followed in the Tube
      Feeding Clinic at the Children's Hospital of Wisconsin from January 1999 to June
      2002 were reviewed. Prevalence of selected nutrient deficiencies were determined
      and their association with growth and caloric intake was measured. One hundred
      fifty patients (60% male) met the inclusion criteria. The mean age of children
      was 7 years 6 months (SD +/- 5 years 4 months). As a proportion of total caloric
      intake, the mean percentage of calories from formula was 92% (+/- 15). No
      deficiencies of vitamins D or E were found. Ferritin concentration below lower
      limits of the age-appropriate range of normal (LLN) was found in 30 of 122 (25%)
      and hemoglobin was below LLN in 12 of 139 (9%). One patient each had vitamin A,
      calcium, phosphorus, and magnesium serum concentrations below LLN. Below normal
      serum zinc was found in 43 of 142 (30%). Ninety-one of 134 patients (68%) had
      below normal selenium levels, and 29 of 126 (23%) had both zinc and selenium
      deficiency. A significant association was found between percentage of recommended
      daily allowance (RDA) of calories received and selenium concentration below LLN.
      Patients with selenium deficiency received a mean of 75% (+/- 21) of the RDA of
      calories for age, whereas patients without deficiency received a mean of 91% (+/-
      19) of the RDA of calories for age (p < 0.0001). There was a negative association
      between deficiency and weight for age: patients with selenium deficiency were 33%
      mean weight for age percentile (+/- 30), compared to 21% (+/- 27, p < 0.05) for
      those without selenium deficiency. There was a negative correlation between the
      percentage of RDA of calories and height for age, weight for age, and weight for
      height (p < 0.05).

PMID- 16429215
TI  - Selective mutism: are primary care physicians missing the silence?
AB  - To survey parents of children with selective mutism (SM) in regard to (1) the
      role of the primary care physician in the diagnosis of SM; (2) the social and
      school consequences of SM; and (3) their opinion of the effectiveness of
      different treatment modalities, a 39-item written survey was mailed to 27 parents
      with at least one child diagnosed with SM on the basis of diagnostic and
      statistical manual IV-text revision (DSM IV-TR) criteria. Twenty-seven parents
      (100%), with a total of 33 children with SM, completed the survey. There were 24
      girls and 9 boys. The mean age when parents had strong concerns about symptoms of
      SM was 3.8 years, but diagnosis did not occur until nearly a year later. Twenty
      three (69.7%) of the children with SM were never diagnosed accurately or referred
      by their primary care physicians. SM caused important school/social problems for
      17 (51.5%) of the children. Speech therapy was provided for 36.4% of children and
      was thought to have been helpful for 30% of them. Behavior modification was the
      treatment for 45.5% of children and perceived to be helpful for 66.7% of them.
      Selective serotonin re-uptake inhibitor pharmacotherapy was prescribed for 17
      (51.5%) of the children and believed to be effective for 11 (65%) of them.
      Primary care physicians in this study rarely diagnosed accurately or referred
      children with SM in a timely fashion, even though symptoms of the condition were
      generally very apparent and parents had expressed concern. Behavioral
      modification, pharmacotherapy with SSRIs, and early intervention are viable
      treatment options. Early diagnosis is key to preventing long-term effects of this
      condition.

PMID- 16429216
TI  - Incidence of meatal stenosis following neonatal circumcision in a primary care
      setting.
AB  - The objective of this study was to prospectively document the incidence of meatal
      stenosis in boys. The study included a consecutive sample of boys whose visit
      with the physician included a genital examination in a private primary care
      pediatric practice in rural northern Wisconsin. Meatal stenosis was diagnosed in
      boys from 1.94 to 12.34 years of age. The diagnosis was made in 24 of 329
      circumcised boys who were Tanner I development and older than 3 years of age
      (7.29%, 95%CI=4.48-10.10%). Nearly all required meatotomy to resolve their
      symptoms. All of the boys with meatal stenosis were circumcised neonatally (exact
      OR=3.54, 95%CI=0.62-infinity). The ratio of circumcised boys to noncircumcised
      boys in this study provided 80% power to demonstrate a 21.4% difference in the
      incidence of meatal stenosis between circumcised and noncircumcised Tanner I boys
      3 years and older. Meatal stenosis may be the most common complication following
      neonatal circumcision. The frequency of this complication and the need for
      surgical correction need to be disclosed as part of the informed consent for
      neonatal circumcision. A careful meatal examination is indicted in any
      circumcised boy with abdominal or urinary complaints.

PMID- 16429217
TI  - A study of family head shape: environment alters cranial shape.
AB  - A change in the type of cranial deformities (plagiocephaly) presenting to certain
      clinics has occurred. The purpose of this study was to compare infant head shapes
      against head shapes of their biologic parents to explore the roles of heredity
      and environment on cranial shape. Standardized family photographs and
      anthropometric measurements demonstrated that 30% of the infants had cranial
      widths 2 standard deviations above norm, while 4.6% had widths exceeding 3
      standard deviations. Despite a mean age of only 8 months, 11.6% had widths that
      were already greater than that of 1 parent. These results demonstrate that
      plagiocephaly has taken on a new configuration, presenting not only with
      asymmetry, but also with excessive cranial width.

PMID- 16429218
TI  - Does a mother singing to her premature baby affect feeding in the neonatal
      intensive care unit?
AB  - Recent studies suggest that premature neonates exposed to music have reduced
      symptoms of stress, faster weight gain, and shorter neonatal intensive care unit
      (NICU) stays. This pilot study attempted to measure contingent effects of
      mothers' singing during feedings. Mothers sang to their babies during 2 of 4
      feedings on 2 consecutive days, logging songs they sang, and subjectively
      evaluating each feeding. Infants' heart and respiration rates were recorded as
      well as duration of feeding and volume of fluid taken orally; feeding velocity
      and percent of feeding goal were calculated. In paired t tests, no significant
      benefits or deterrents assignable to the singing were observed.

PMID- 16429219
TI  - Safe removal of upper esophageal coins by using Magill forceps: two centers'
      experience.
AB  - Coin ingestion with subsequent esophageal coin impaction is common in children.
      Considerable debate surrounds the choice of technique for the removal of
      esophageal coins. This study demonstrates a minimally invasive technique for
      upper esophageal coin extraction. A retrospective review was conducted of 165
      children who had upper esophageal coins extracted by using a Magill forceps. One
      hundred fifty-six coins (96.4%) were successfully removed without any
      complications. The average time taken to remove the coin was 33 seconds. Use of
      the Magill forceps technique minimizes instrumentation of the esophagus and is an
      easy, safe technique for removing coins from the upper end of the esophagus.

PMID- 16429220
TI  - FDA labeling status of pediatric medications.

PMID- 16429221
TI  - Strengthening tobacco-related messages relayed in pediatric offices in Delaware:
      results of a pilot intervention.

PMID- 16429222
TI  - A case of tuberculous otitis media.

PMID- 16429223
TI  - Referred knee pain in posterior dislocation of the hip.

PMID- 16429224
TI  - Cushing syndrome from topical foam steroid use in an adolescent male.

PMID- 16429225
TI  - Bronchiolitis with hyponatremia.

PMID- 16429226
TI  - Bronchiolitis with hyponatremia. Commentary.

PMID- 16429227
TI  - Hematemesis in a neonate.

PMID- 16429228
TI  - Hematemesis in a neonate. Commentary.

PMID- 16429229
TI  - Depo-Provera.

PMID- 16429231
TI  - Austronesian origin of the 27-bp deletion of the erythrocyte band 3 gene in East
      Sepik, Papua New Guinea inferred from mtDNA analysis.
AB  - The 27-bp deletion in the erythrocyte band 3 gene (B3Delta27) constitutes a
      genetic basis for Southeast Asian and Melanesian ovalocytosis. The distribution
      of B3Delta27 has been interpreted to reflect malaria selection or dispersal of
      the recent expansion of Austronesian-speaking populations. To explore these two
      hypotheses, we examined eight malarious populations of the East Sepik Province of
      Papua New Guinea (PNG) that speak both the Austronesian and Papuan languages. The
      B3Delta27 allele frequencies within populations were not positively correlated
      with malaria endemicities. In contrast, statistically significant geographical
      variations in the B3Delta27 allele distribution were observed. B3Delta27 was high
      (0.06-0.07) in the islands, intermediate (0.02-0.03) in coastal regions, but was
      absent or rare (0.00-0.01) in inland populations. Furthermore, the prevalence of
      the mitochondrial DNA region V 9-bp deletion, associated with the Austronesian
      expansion, was significantly correlated with that of B3Delta27. These results
      suggest that B3Delta27 was introduced by Austronesian-speaking people within the
      past 3,500 years and subsequently expanded to populations along the coasts and
      islands of PNG. This study highlights the contribution of population origins,
      patterns of gene flow, disease selection and genetic drift in determining the
      genetic compositions of present populations.

PMID- 16429232
TI  - Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role
      in the imprinting establishment of the mouse 7C imprinting domain.
AB  - The human chromosome 15q11-q13, or mouse chromosome 7C, is an imprinting domain
      controlled by bipartite imprinting centers (ICs): Prader-Willi syndrome (PWS)-IC
      and Angelman syndrome (AS)-IC. PWS-IC functions to maintain the paternal
      epigenotype on the paternal chromosome in somatic cells, while AS-IC plays a role
      in the establishment of the maternal epigenetic mark at PWS-IC in the female
      germline or early embryos. Several alternative exons and promoters of Snurf-Snrpn
      (SNRPN upstream reading frame-small nuclear ribonucleoprotein polypeptide N) are
      expressed as "IC transcripts". Previous studies have shown that IC-transcript
      expression is restricted to the brain. We studied expression of the mouse IC
      transcript in tissues including brain and oocytes as well as in cultured neurons
      and glia cells by RT-PCR and by in situ hybridization (ISH) in oocytes. The IC
      transcript was strongly expressed in brain (especially in neurons) and ovary
      (especially in oocytes and granulosa cells), while no expression was found in
      other tissues. This was confirmed by quantitative analysis and ISH. Expression
      levels in the brain were 7-fold higher compared to those in ovaries. ISH signals
      were observed in oocytes and granulosa cells of the secondary and developing
      follicles. These findings, together with previous data, suggest that the IC
      transcript may be associated with the establishment of PWS-IC methylation on the
      maternal chromosome as an AS-IC cis-acting element.

PMID- 16429233
TI  - Association of IL8, CXCR2 and TNF-alpha polymorphisms and airway disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a disease characterised by
      inflammation of the peripheral airways involving many inflammatory cells and
      mediators. IL8 is an important inflammatory mediator that is responsible for the
      migration and activation of neutrophils. Cellular activity of IL8 is mediated by
      the receptor CXCR2, and transcription of IL8 is controlled by the cytokine tumour
      necrosis factor (TNFalpha). The aim of our study was to investigate the influence
      of single nucleotide polymorphisms in IL8, CXCR2 and TNF-alpha on lung function
      and respiratory symptoms in subjects from Melbourne, Australia. A total of 1,232
      participants completed a detailed respiratory questionnaire, spirometry and
      measurement of gas transfer. Genotyping for the IL8 -251 T-->A, CXCR2 +785C-->T
      and TNF-alpha -308G-->A polymorphisms was performed using the tetra-primer ARMS
      PCR method. The TNF-alpha A allele was associated with a reduced FEF(25-75) (P =
      0.03). Inheritance of the CXCR2 T allele was associated with significantly higher
      diffusing capacity (P = 0.03) and FEF(25-75) (P = 0.02). No association with the
      IL8 -251 polymorphism was found. Our results suggest that TNF-alpha is associated
      with COPD-related phenotypes and the CXCR2 +785 SNP may be important in
      protecting against pulmonary inflammation. These genes may be important
      candidates in the modulation of the inflammatory response in the airways.

PMID- 16429234
TI  - Spontaneous basilar-membrane oscillation (SBMO) and coherent reflection.
AB  - In a previous report (in JARO) we have described a relatively high-frequency (15
      kHz) spontaneous oscillation of the basilar membrane (SBMO) in a guinea pig ear;
      this oscillation was accompanied by a spontaneous otoacoustic emission (SOAE) at
      the same frequency. During the spontaneous oscillation and after it had subsided,
      the mechanical frequency response of the basilar membrane was measured by way of
      a wide-band random-noise stimulus, and it showed a number of spectral peaks, one
      of which having the frequency of the original oscillation. This pattern of peaks
      cannot be explained by assuming a single place of reflection in the cochlea. In
      this paper the process of 'coherent reflection' is artificially evoked in a three
      dimensional model of the cochlea by imposing random place-fixed irregularities to
      the basilar-membrane impedance. It is shown that in the model a series of peaks
      arises in the frequency spectrum of the basilar-membrane response which
      phenomenon resembles the one found in the experimental animal. It is also shown
      that these peaks are actually due to superposition of the primary wave and a wave
      resulting from 'coherent reflection' which is reflected at the stapes. When the
      intensity of the acoustic stimulus signal is increased, the relative sizes of
      these peaks in the simulation diminish in about the same way as in the
      experiment. It is concluded that coherent reflection most likely is the cause of
      the 'extra peaks', and that this concept can also explain the observed level
      dependence of these peaks. The findings of this study lead to a minor refinement
      regarding the actual requirements for coherent reflection to arise.

PMID- 16429235
TI  - A positive correlation between homocysteine and brachial-ankle pulse wave
      velocity in patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is associated with premature atherothrombotic
      complications. Hyperhomocysteinemia is considered a cardiovascular risk factor.
      Increased vascular stiffness may increase cardiovascular mortality. Pulse wave
      velocity (PWV) is a noninvasive method of analyzing vascular stiffness in the
      assessment of atherosclerosis. The objective of this study was to identify the
      relationship between plasma homocysteine levels and brachial-ankle pulse wave
      velocity (baPWV) measurement in SLE. Plasma homocysteine, baPWV, ankle-brachial
      index, blood pressure, C3, C4, anticardiolipin antibody (aCL), and anti-double
      stranded DNA antibodies were determined in a total of 58 female patients with
      SLE. The control group comprised 32 age-matched healthy females. In addition, all
      patients were further classified into subgroups according to the presence of aCL
      (SLE/aCL+, n=27 vs SLE/aCL-, n=31) to determine the effect of aCL on the tested
      variables. The mean values for plasma homocysteine and baPWV were 13.19 mumol/l
      and 1,482 cm/s, respectively. Plasma homocysteine levels were significantly
      elevated in SLE patients when compared with the healthy controls. SLE patients
      with aCL had a significantly higher plasma homocysteine level than those without
      aCL. A significant positive correlation between plasma homocysteine and baPWV was
      found in patients with SLE (r=0.335, P=0.028, n=58). Plasma homocysteine also
      significantly correlated with right baPWV in all SLE patients (r=0.371, P=0.014,
      n=58) and in the SLE/aCL+ group (r=0.523, P=0.031, n=27). These findings indicate
      a possible link between plasma homocysteine and baPWV in SLE. In conclusion, SLE
      patients had an increased level of plasma homocysteine, and this phenomenon
      appeared to be related to vascular stiffness.

PMID- 16429236
TI  - How could we make a diagnosis of Wegener's granulomatosis?
AB  - Current classification criteria function poorly in diagnosing Wegener's
      granulomatosis (WG). In this study, we presented a patient with sinonasal
      symptoms, hematuria, and proteinuria, who had been misdiagnosed as a patient
      suffering from WG, but finally turned out to be a patient suffering from non
      Hodgkin's T cell lymphoma. Diagnostic approach of WG was also discussed.

PMID- 16429237
TI  - Remission of rheumatoid arthritis after acute disseminated varicella-zoster
      infection.
AB  - A 65-year-old immunocompetent male presented with symmetric polyarthritis of 12
      weeks and paresthesias in the distribution of the left median nerve distribution
      of 4 weeks duration. He had tender joint count of 20 and swollen joint count of
      12. He was positive for rheumatoid factor and his erythrocyte sedimentation rate
      was 52 mm. Nerve conduction study demonstrated polyneuropathy. Radiographs showed
      severe juxta articular osteopenia at the wrist and the metacarpophalangeal
      joints. He received methotrexate of 10 mg/week and prednisolone of 0.15 mg/kg/day
      along with nonsteroidal antiinflammatory drugs (NSAIDs) with a diagnosis of
      seropositive rheumatoid arthritis (RA). Thirteen weeks after therapy, he
      presented to the outpatient clinic with disseminated vesicular eruptions all over
      his body with erythematous base and pneumonia involving the left upper lobe.
      Tzanck smear from the lesions and serology (IgG) for varicella-virus infection
      were positive. A diagnosis of acute disseminated varicella zoster with pneumonia
      was made. The patient improved on parenteral acyclovir and broad-spectrum
      antibiotics. With the improvement in rash and pneumonia after 2 weeks, the
      patient noticed a marked improvement in the joint symptoms. Arthritis remained in
      remission without the need for any disease-modifying drug or NSAID for next the
      24 months and continued to be so until the last follow-up. Our case presents a
      unique phenomenon of RA remission after disseminated varicella-zoster infection
      in an immunocompetent individual.

PMID- 16429238
TI  - Pauciarticular severe destructive arthropathy in a child secondary to synovial
      osteochondromatosis.

PMID- 16429239
TI  - Carpal collapse in patients with rheumatoid arthritis.
AB  - The inflammation of the wrist and carpal collapse play an important role in the
      deformity of the rheumatoid hand and leads to functional limitation. The aim of
      this study was to evaluate carpal collapse and related clinical variables in
      patients with rheumatoid arthritis (RA). Carpal height ratio (CHR) indicating the
      degree of carpal collapse was measured in 33 female RA patients with a mean age
      of 41.9+/-10.3 years and 30 female healthy control subjects with a mean age of
      40.5+/-9.2 years. The normal range of the carpal collapse was defined in our
      study population and the incidence of carpal collapse was determined. The
      correlation between carpal collapse and clinical and laboratory variables
      including pain by visual analog scale, Ritchie articular index, erythrocyte
      sedimentation rate, C-reactive protein, health assessment questionnaire
      indicating functional status, and Larsen roentgenological evaluation were
      determined. Subgroup analyses were also performed in patients with and without
      carpal collapse. The mean disease duration of the patients was 12.4+/-5.5 years.
      The mean CHR index of the patients was significantly lower than in the control
      group (0.47+/-4.3 and 0.54+/-1.4 respectively). CHR <0.48 was defined as carpal
      collapse in our study group. Seventeen patients (51.5%) had carpal collapse in
      the patient group. None of the clinical or laboratory variables except levels of
      disease duration and Larsen score was correlated with carpal collapse as
      represented by CHR. The best related clinical variable with carpal collapse was
      found as duration of disease. The mean duration of disease and the Larsen score
      were significantly higher in patients with carpal collapse than those without
      collapse. Other clinical parameters and functional status were similar between
      patients with and without carpal collapse. In conclusion, although various
      clinical parameters and functional disability in patients with RA may not be
      correlated with radiological malalignment, the carpal collapse may be more common
      in RA than is generally recognized.

PMID- 16429240
TI  - Headache may be a risk factor for complex regional pain syndrome.
AB  - We investigated whether headache and family history of headache are risk factors
      for complex regional pain syndrome (CRPS) or not. Twenty-three CRPS patients and
      69 healthy persons were interviewed whether or not they suffered from headache
      and had first-degree family history of headache. A headache sufferer was defined
      as a person who regularly suffered from headache for more than 2 days per month.
      Headache after an occurrence of CRPS (headache after an injury or operation in
      case of CRPS after an injury or operation) was excluded and just headache before
      an occurrence of CRPS was included. If a first-degree family had a regular
      headache, she or he was regarded as a headache sufferer regardless of the
      frequency of headache. Of the 23 patients with CRPS, 12 (52.2%) had suffered from
      headache before an occurrence of CRPS. Of the 69 healthy persons, 18 (26.1%)
      suffered from headache. Significant differences between patients and healthy
      persons were found. Of the 23 patients with CRPS, eight (34.8%) had a first
      degree family history of headache. Of the 69 healthy persons, ten (14.5%) had a
      first-degree family history of headache. Significant differences between patients
      and healthy persons were found in a family history. The results suggest that
      headache and a first-degree family history of headache are risk factors for CRPS.
      To determine whether or not headache and first-degree family history of headache
      are risk factors for CRPS, further prospective studies with larger patient
      numbers should be carried out.

PMID- 16429241
TI  - Lupus erythematosus and lupus valgaris: a case report and historical remarks.
AB  - Lupus erythematosus and lupus valgaris, i.e., cutaneous tuberculosis, are
      confusing skin lesions in the history. Here, we reported on a Chinese lupus
      patient manifested with multiple nodular erythematous rashes on both upper
      extremities, which turned out to be cutaneous mycobacterial infection.

PMID- 16429243
TI  - Case report: Morgagni hernia.
AB  - The case reported here is a 32-year-old man with a sudden onset of chest pain and
      an acute deterioration of lung function. An incarcerated Morgagni hernia was
      diagnosed with a computer tomographic CT scan, and repaired electively via a
      midline laparotomy. Morgagni hernia is a rare type of congenital diaphragmatic
      hernia, which may not be symptomatic until adulthood when the patient presents
      with acute symptoms or incarceration.

PMID- 16429242
TI  - Plasmapheresis therapy in an elderly patient with rapidly progressive Henoch
      Schonlein purpura with disseminated organ involvement.
AB  - Henoch-Schonlein purpura (HSP) frequently occurs in children below the age of 15
      years and is rare with increasing age. Prognosis and therapy largely depend on
      the clinical presentation. The disease may be preceded by an upper respiratory
      tract infection, and drugs have also been implicated in the pathogenesis of the
      disease. Most children recover from the illness, whereas 40% of adults have
      persistent hematuria and 10% develop chronic renal failure. Recent studies
      strongly suggest that adults with HSP should be monitored for prolonged periods
      and treated aggressively. Here, we present a case of a patient with HSP who
      developed multiorgan failure requiring assistance in breathing and dialysis, and
      also sustained gastrointestinal bleeding despite aggressive immunosuppressive
      therapy. In analogy to published data in children with severe HSP, the patient
      was treated by plasma exchange in combination with low dose oral
      cyclophosphamide, while high dose steroids were reduced over time. The patient
      could be discharged 70 days after admission. One year after discharge, the
      patient is doing well without any signs of activity of HSP and completely
      unremarkable renal function. The maintenance daily dose of steroids is 7.5 mg.

PMID- 16429245
TI  - Shared decision-making and evidence-based practice: a commentary.

PMID- 16429244
TI  - Various surgical approaches to treat voiding dysfunction following anti
      incontinence surgery.
AB  - OBJECTIVE: The aims of this study are to report the efficacy of retropubic
      urethrolysis, vaginal urethrolysis, and cutting of synthetic suburethral slings
      in treating postoperative voiding dysfunction that occurs after anti-incontinence
      surgery and to report the recurrence rate of stress urinary incontinence (SUI).
      METHODS: All patients from January 1996 to October 2003 who presented with
      voiding dysfunction following an anti-incontinence procedure and who subsequently
      underwent either retropubic urethrolysis, vaginal urethrolysis, or synthetic
      suburethral sling takedown were included in the study. Pre- and postoperative
      irritative symptoms (urinary frequency or urgency), obstructive symptoms
      (hesitancy, voiding difficulty, and incomplete emptying), and stress urinary
      incontinence symptoms were obtained in a standardized fashion. The Incontinence
      Impact Questionnaire and Urogenital Distres Invetory quality of life (QOL)
      questionnaires were also obtained to objectify these symptoms. Other objective
      postoperative analysis included simple uroflowmetry, measurement of postvoid
      residual (PVR), and simple or subtracted cystometry. RESULTS: Forty-four patients
      were included in the study (suburethral sling takedown = 14, vaginal urethrolysis
      = 20, and retropubic urethrolysis = 10), 77% of whom had objective follow-up.
      Preoperatively, 31 patients (70.5%) had irritative symptoms, 41 (93.2%) had
      obstructive symptoms, and 6 (13.6%) had symptoms of stress urinary incontinence
      (SUI), while postoperatively, these symptoms were found in 30 (68.2%), 11
      (25.0%), and 18 (40.9%), respectively. Postoperatively, 6 patients (17.6%) had a
      PVR > 100 cc, 5 patients (14.7%) had a bladder contractions, and 16 patients
      (47.1%) demonstrated the sign or diagnosis of (SUI). Additionally, there was a
      statistically significant improvement in both QOL questionnaires. CONCLUSIONS:
      Various surgical approaches may be used to treat voiding dysfunction following an
      anti-incontinence procedure. Following a vaginal or retropubic urethrolysis or
      takedown of a synthetic suburethral sling, obstructive symptoms are likely to
      improve, irritative symptoms may remain unchanged, and almost half will develop
      recurrence of SUI.

PMID- 16429246
TI  - Racial differences in the use of antidepressants and counseling for depression
      among homeless women.
AB  - The purpose of the current study was to examine how African American race was
      related to the use of antidepressants and counseling among homeless depressed
      women. Women were recruited in 18 homeless shelters in four counties in central
      North Carolina. Head of household homeless mothers with psychiatric and/or
      substance abuse disorders who had dependent children were eligible to
      participate. One hundred and sixty four women enrolled into the study. Fifty-six
      percent (N=92) of the homeless women were currently depressed at the time of
      enrollment into the study. Nineteen of the depressed women reported having
      received counseling during the past 3 months and there were no racial differences
      in counseling use. A total of 19 depressed women were currently taking
      antidepressants. Non-Black depressed women (60%) were significantly more likely
      than Black depressed women (16%) to be currently using antidepressant medication
      (OR=0.14, 95% CI=0.02, 0.90). Fourteen of the 92 depressed women reported needing
      mental health services but not receiving them during the past 3 months and all of
      these women were Black.

PMID- 16429247
TI  - Rural African-American women who use cocaine: needs and future aspirations
      related to their mothering role.
AB  - The overall purpose of this ethnographic study was to understand the culture of
      rural African-American women who use cocaine, with this report focusing on their
      perceived mothering needs and future aspirations. Three semi-structured
      interviews and participant observations were conducted over four years with 30
      respondents, of which 24 were mothers. Data for this article were derived from
      the 21 mothers who cared for dependent children. Four mothering-related needs
      (escape from boredom, others to help mother for them, not having others' children
      to mother, and having children to "keep them going") and two categories of
      mothering-related aspirations (child-focused or self-focused) were identified.
      Given the limited resources in the area, an unexpected finding was the absence of
      some needs and aspirations. Theoretical explanations for the themes identified as
      well as those not identified are posited, and practice and research implications
      are presented.

PMID- 16429249
TI  - Impact of maternal mental health status on child mental health treatment outcome.
AB  - This study examined the effect of maternal depression and anxiety on child
      treatment outcome. Psychiatric assessments were conducted on 180 mother-child
      pairs when the child entered treatment in a community mental health center and
      six months later. Children whose mothers were depressed or anxious were
      significantly more impaired than children of mentally healthy mothers at both
      time points. Both groups of children improved at approximately the same rate. The
      findings suggest that early mental health screening of children and their mothers
      may be important preventive practices. Addressing the mental health needs of
      mothers and children simultaneously may be an effective method of reducing their
      mental health problems.

PMID- 16429248
TI  - Shared decision-making and evidence-based practice.
AB  - Shared decision-making refers to a process of health care delivery in which
      practitioners and clients seeking help for problems or disorders collaborate to
      access relevant information and to enable client-centered selection of health
      care resources. Though nearly all clients express a desire for more information,
      preferences for participation in health care decisions vary by individual and by
      illness. Two common strategies to promote shared decision-making are
      communication training for clients and clinicians, and decision aids to provide
      targeted information and values clarification. Research in several areas of
      medicine shows that active client participation results in a variety of benefits,
      from increased satisfaction to decreased symptom burden. Many current mental
      health interventions promote client-centered care, client choice, and self
      directed care, but research on shared decision-making in mental health for
      clients with severe and persistent mental illness is just beginning.

PMID- 16429250
TI  - Group debriefing for people with chronic diseases during the SARS pandemic:
      Strength-Focused and Meaning-Oriented Approach for Resilience and Transformation
      (SMART).
AB  - This study presented preliminary results on the efficacy of a novel group
      debriefing model called Strength-Focused and Meaning-Oriented Approach for
      Resilience and Transformation (SMART). The SMART debriefing (1) aimed at boosting
      resilience and catalyzing transformation among persons undergoing stressful
      events, (2) adopted a growth-oriented and holistic approach of health promotion,
      and (3) employed methods drawn from various indigenous sources (e.g. Asian
      philosophies and Traditional Chinese Medicine). Participants (N=51) were people
      with chronic diseases recruited about 1 month (August 2003) after the Severe
      Acute Respiratory Syndrome (SARS) outbreak was eventually under control, after
      causing widespread panic in Hong Kong. After the one-day group debriefing,
      participants showed significant decrease in depression level, as measured by
      Brief Symptom Inventory (Derogatis & Melisaratos, 1983, Psychological Medicine,
      13(3), 595-605) and changes in cognitive appraisal towards SARS. Such changes
      were sustained in a 1-month follow-up. Clinical implications and directions for
      further study were discussed.

PMID- 16429251
TI  - Conditions associated with identification of mentally ill youths in juvenile
      detention.
AB  - The current study examines the prevalence and severity of psychiatric symptoms in
      incarcerated youth. A random sample of youth ages 13-17 who were referred for
      mental health services (n=120) and not referred for services (n=120) at a
      juvenile detention facility were studied. Psychopathology was evaluated using the
      Diagnostic Interview Schedule for Children and the Child Behavior Checklist.
      Ninety-six percent of referred youth and 69% of non-referred youth had one or
      more psychiatric diagnoses. Co-morbidity was common in both groups. The findings
      suggest that youths in the juvenile justice system have noteworthy
      psychopathology that often remains unidentified.

PMID- 16429253
TI  - The effect of various inflammatory agents on the alternative metabolic pathways
      of arginine in mouse and rat macrophages.
AB  - OBJECTIVE AND DESIGN: The effects of various inflammatory stimuli on the
      alternative arginine metabolic pathways in mouse and rat peritoneal macrophages
      were investigated in vitro and compared. TREATMENTS: Mice and rats were injected
      i. p. with thioglycollate, carrageenan, casein, BCG and Newcastle Disease Virus
      (NDV) vaccines. METHODS: Peritoneal macrophages were isolated from untreated and
      treated animals. The activities of nitric oxide synthase (NOS) II and arginase
      were measured and expressions were followed by Western blotting. The uptake of
      arginine and nitrite formation of macrophages were also measured. RESULTS:
      Inflammatory stimuli increased the NO production and the expression and activity
      of both NOS II and arginase in mice in vitro. On the contrary, the same
      treatments changed the expression and activity of NOS II only, but not those of
      arginase in rats. The most marked effects on NO metabolism were produced by
      casein and NDV treatments. CONCLUSIONS: The activity and expression of NOS II and
      arginase can be stimulated in peritoneal macrophages in vitro by injecting
      inflammatory agents into the peritoneal cavity. A markedly different response in
      arginine metabolism was observed in mouse and rat macrophages. Casein treatment
      was a potent inducer for both enzymes. NDV vaccines induced mainly NOS II, while
      thioglycollate induced arginase.

PMID- 16429254
TI  - Osteoprotegerin reduces the loss of periarticular bone mass in primary and
      secondary spongiosa but does not influence inflammation in rat antigen-induced
      arthritis.
AB  - OBJECTIVE: To assess the effect of osteoprotegerin (OPG) on joint swelling,
      synovial inflammation and cartilage destruction, periarticular and axial bone
      volume, and bone turnover in rat antigen-induced arthritis (AIA). DESIGN: Rats
      were treated with OPG (3 mg/kg/day) at regular intervals from day 1 to day 20 of
      AIA. Disease activity was evaluated by measurement of joint swelling as well as,
      joint inflammation and destruction by histology. Bone volume and cellular
      turnover parameters of secondary spongiosa of the right tibia head and the third
      lumbar vertebra were evaluated by histomorphometry. Periarticular bone volume of
      the primary spongiosa at the right tibia head was measured by linear scanning.
      The findings were compared with those of PBS-treated AIA and healthy animals.
      RESULT: OPG treatment did not reduce joint swelling or histological signs of
      inflammation. Cartilage destruction was reduced. However, this effect did not
      reach statistical significance . In the secondary spongiosa OPG treatment reduced
      the loss of periarticular bone volume. However, the latter did not reach the
      level of healthy controls. OPG treatment significantly reduced parameters of bone
      formation and bone resorption. In the primary spongiosa, OPG-treatment led to a
      higher amount of mineralized tissue and a greater number of trabeculae compared
      to PBS-treated animals with AIA or healthy controls. In the axial skeleton, OPG
      treatment reduced bone formation and bone resorption parameters compared to
      healthy animals. This treatment had no influence on bone volume. CONCLUSIONS: In
      periarticular bone of AIA rats, OPG treatment reduced the loss of bone volume and
      decreased the bone turnover, thus preventing periarticular bone destruction. OPG
      treatment had no influence on inflammatory process or on cartilage destruction.

PMID- 16429255
TI  - Spontaneous recovery of injured Achilles tendon in inducible nitric oxide
      synthase gene knockout mice.
AB  - OBJECTIVE AND DESIGN: To determine if inducible nitric oxide synthase (iNOS) gene
      could affect Achilles tendon healing using iNOS gene knockout mice. METHODS: 21
      iNOS knockout (iNOS(-/-)) mice and 8 of the wild type (iNOS(+/+)) mice were
      utilized in this study. Group 1: iNOS(+/+) mice (n = 8), group 2: iNOS(-/-) mice
      (n = 11) and group 3: iNOS(-/-) with a NOS inhibitor, (aminoguanidine, 500
      mg/kg/day, via an intraperitoneal mini-osmotic pump for 7 days, n = 10). The
      right Achilles tendon was transected in all mice and harvested on day 7 for cross
      sectional area and biomechanical properties. Serum nitrate concentration of the
      mice was measured by gas chromatography mass spectrometry (GC/MS). RESULTS: A
      significant reduction in cross-sectional area of the healing Achilles tendon was
      observed in group 3 mice compared to group 2 mice (p < 0.01). The serum nitrate
      concentration in both group 2 and group 3 mice was lower than that in group 1
      mice (p < 0.01) iNOS gene deletion and inhibition of NOS did not affect the
      biomechanical properties of the healing tendons. CONCLUSIONS: iNOS gene is not
      solely responsible for the beneficial effects of nitric oxide (NO) on tendon
      healing.

PMID- 16429256
TI  - Equine CCL11 induces eosinophil cytoskeletal reorganization and activation.
AB  - OBJECTIVES: To assess the biological effects of purified recombinant equine CCL11
      on equine eosinophil function. METHODS: Following stimulation of eosinophils from
      normal horses, the polymerised form of actin was measured by flow cytometry using
      fluorescently labelled phalloidin. Migration was determined in a 96 well plate
      chemotaxis assay using 8 microm pore membranes, and adherence of eosinophils to
      serum-coated plastic was assessed using a colorimetric assay for eosinophil
      peroxidase. Superoxide generation was measured by the reduction of cytochrome C
      in a colorimetric assay. RESULTS: Equine CCL11 induced significant (p < 0.001),
      concentration-dependent actin polymerisation and migration of equine eosinophils.
      Stimulation with CCL11 did not induce significant adherence to serum coated
      plastic, or superoxide production. CONCLUSIONS: Equine CCL11 stimulates
      cytoskeletal reorganization and migration of equine eosinophils, suggesting that
      it may be involved in the regulation of eosinophil trafficking in horses.

PMID- 16429257
TI  - Post-transcriptional gene silencing of the p23 silencing suppressor of Citrus
      tristeza virus confers resistance to the virus in transgenic Mexican lime.
AB  - Previously, we have shown that most Mexican limes (Citrus aurantifolia (Christ.)
      Swing.) expressing the p23 gene of Citrus tristeza virus (CTV) exhibit
      aberrations resembling viral leaf symptoms. Here we report that five independent
      transgenic lines having normal phenotype displayed characteristics typical of
      post-transcriptional gene silencing (PTGS): multiple copies of the transgene, low
      levels of the corresponding mRNA, methylation of the silenced transgene, and
      accumulation of p23-specific small interfering RNAs (siRNAs). When graft- or
      aphid-inoculated with CTV, some propagations of these silenced lines were immune:
      they neither expressed symptoms nor accumulated virions and viral RNA as
      estimated by DAS-ELISA and Northern blot hybridization, respectively. Other
      propagations were moderately resistant because they became infected later and
      showed attenuated symptoms compared to controls. The susceptible propagations, in
      addition to symptom expression and elevated virus titer, accumulated p23-specific
      siRNAs at levels significantly higher than immune or non-inoculated propagations,
      and showed transgene demethylation. This variable response among clonal
      transformants indicates that factors other than the genetic background of the
      transgenic plants play a key role in PTGS-mediated resistance.

PMID- 16429259
TI  - Comparative structural and functional characterization of sorghum and maize
      duplications containing orthologous myb transcription regulators of 3
      deoxyflavonoid biosynthesis.
AB  - Sequence characterization of the genomic region of sorghum yellow seed 1 shows
      the presence of two genes that are arranged in a head to tail orientation. The
      two duplicated gene copies, y1 and y2 are separated by a 9.084 kbp intergenic
      region, which is largely composed of highly repetitive sequences. The y1 is the
      functional copy, while the y2 may represent a pseudogene; there are several
      sequence indels and rearrangements within the putative coding region of y2. The
      y1 gene encodes a R2R3 type of Myb domain protein that regulates the expression
      of chalcone synthase, chalcone isomerase and dihydroflavonol reductase genes
      required for the biosynthesis of 3-deoxyflavonoids. Expression of y1 can be
      observed throughout the plant and it represents a combination of expression
      patterns produced by different alleles of the maize p1. Comparative sequence
      analysis within the coding regions and flanking sequences of y1, y2 and their
      maize and teosinte orthologs show local rearrangements and insertions that may
      have created modified regulatory regions. These micro-colinearity modifications
      possibly are responsible for differential patterns of expression in maize and
      sorghum floral and vegetative tissues. Phylogenetic analysis indicates that
      sorghum y1 and y2 sequences may have arisen by gene duplication mechanisms and
      represent an evolutionarily parallel event to the duplication of maize p2 and p1
      genes.

PMID- 16429258
TI  - Isolation and characterization of genes associated to cotton somatic
      embryogenesis by suppression subtractive hybridization and macroarray.
AB  - Somatic embryogenesis (SE) is the developmental reprogramming of somatic cells
      toward the embryogenesis pathway and is a notable illustration of cell
      totipotency. To identify genes involved in SE, subtractive polymerase chain
      reaction (PCR) was performed to generate transcripts highly enriched for SE
      related genes, using cDNA prepared from a mixture of embryogenic callus and pre
      globular somatic embryos, as the tester, and cDNA from non-embryogenic callus, as
      the driver. After differential screening and subsequent confirmation by reverse
      Northern blot analysis, a total of 671 differentially expressed cDNA fragments
      were identified, and 242 uni-genes significantly up-regulated during cotton SE
      were recovered, as confirmed by Northern blot and reverse-transcription PCR
      analysis of representative cases, including most previously published SE-related
      genes in plants. In total, more than half had not been identified previously as
      SE-related genes, including dominant crucial genes involved in transcription,
      post-transcription, and transportation, and about one-third had not been reported
      previously to GenBank or were expected to be unknown, or newly identified genes.
      We used cDNA arrays to further investigate the expression patterns of these genes
      in differentiating gradient culture, ranging from pro-embryogenic masses to
      somatic embryos at every stage. The cDNA collection is composed of a broad
      repertoire of SE genes which is an important resource for understanding the
      genetic interactions underlying SE signaling and regulation. Our results
      suggested that a complicated and concerted mechanism involving multiple cellular
      pathways is responsible for cotton SE. This report represents a systematic and
      comprehensive analysis of genes involved in the process of somatic embryogenesis.

PMID- 16429260
TI  - Ordered assembly of mitochondria during rice germination begins with pro
      mitochondrial structures rich in components of the protein import apparatus.
AB  - Mitochondrial maturation during imbibition of rice embryos follows the transition
      of unstructured double membrane bound pro-mitochondria to the typical cristae
      rich mitochondrial structures observed in mature plant cells. During the first 48
      h following imbibition, an ordered increase in the abundance of transcripts
      encoding mitochondrial proteins was observed. Co-incident with these changes in
      transcript levels was dynamic and rapid changes in mitochondrial protein content
      and mitochondrial function. Proteins representing components of the mitochondrial
      protein import apparatus are strikingly abundant in dry seeds, and a functional
      import apparatus was shown to operate 2 h after imbibition. Interestingly, this
      import process was best driven by the oxidation of NADH from outside the
      mitochondrial inner membrane. In later developmental stages the capacity for
      matrix organic acid metabolism was evident, accompanied by the appearance of
      proteins for TCA cycle components, and coordination of electron transport chain
      assembly through components encoded in both mitochondrial and nuclear genomes.
      Together these events provide new insights into the understanding of
      mitochondrial maturation and the nature of pro-mitochondrial structures in plant
      cells.

PMID- 16429261
TI  - Expression enhancement of a rice polyubiquitin gene promoter.
AB  - An 808 bp promoter from a rice polyubiquitin gene, rubi3, has been isolated. The
      rubi3 gene contained an open reading frame of 1,140 bp encoding a pentameric
      polyubiquitin arranged as five tandem, head-to-tail repeats of 76 aa. The 1,140
      bp 5' UTR intron of the gene enhanced its promoter activity in transient
      expression assays by 20-fold. Translational fusion of the GUS reporter gene to
      the coding sequence of the ubiquitin monomer enhanced GUS enzyme activity in
      transient expression assays by 4.3-fold over the construct containing the
      original rubi3 promoter (including the 5' UTR intron) construct. The enhancing
      effect residing in the ubiquitin monomer coding sequence has been narrowed down
      to the first 9 nt coding for the first three amino acid residues of the ubiquitin
      protein. Mutagenesis at the third nucleotide of this 9 nt sequence still
      maintains the enhancing effect, but leads to translation of the native GUS
      protein rather than a fusion protein. The resultant 5' regulatory sequence,
      consisting of the rubi3 promoter, 5' UTR exon and intron, and the mutated first 9
      nt coding sequence, has an activity nearly 90-fold greater than the rubi3
      promoter only (without the 5' UTR intron), and 2.2-fold greater than the maize
      Ubi1 gene promoter (including its 5' UTR intron). The newly created expression
      vector is expected to enhance transgene expression in monocot plants. Considering
      the high conservation of the polyubiquitin gene structure in higher plants, the
      observed enhancement in gene expression may apply to 5' regulatory sequences of
      other plant polyubiquitin genes.

PMID- 16429262
TI  - AtSAP18, an orthologue of human SAP18, is involved in the regulation of salt
      stress and mediates transcriptional repression in Arabidopsis.
AB  - In yeast and mammalian systems, it is well established that transcriptional down
      regulation by DNA-binding repressors involves core histone deacetylation,
      mediated by their interaction within a complex containing histone deacetylase
      (e.g. HDA1), as well as various other proteins (e.g. SIN3, SAP18, SAP30, and
      RbAp46). Here we identify that a Arabidopsis thaliana gene related in sequence to
      SAP18, designated AtSAP18, functions in transcription regulation in plants
      subjected to salt stress. The AtSAP18 loss- of-function mutant is more sensitive
      to NaCl, and is impaired in chlorophyll synthesis as compared to the wild-type.
      Using GST pull-down, two-hybrid, and transient transcription assays, we have
      characterized SAP18 and HDA1 orthologues and provide evidence that SAP18 and HDA1
      function as transcriptional repressors. We further demonstrate that they
      associate with Ethylene-Responsive Element binding Factors (ERFs) to create a
      hormone-sensitive multimeric repressor complex under conditions of environmental
      stress. Our results indicate that AtSAP18 functions to link the HDA complex to
      transcriptional repressors that are bound to chromatin in a sequence-specific
      manner, thereby providing the specificity of signal transduction accompanying
      transcriptional repression under stress conditions.

PMID- 16429263
TI  - Gene structure and expression pattern analysis of three monodehydroascorbate
      reductase (Mdhar) genes in Physcomitrella patens: implications for the evolution
      of the MDHAR family in plants.
AB  - The ascorbate-glutathione pathway plays a major role in the detoxification of
      reactive oxygen species (ROS) in vascular plants. One of the key enzymes in this
      pathway is monodehydroascorbate reductase (MDHAR), a FAD enzyme that catalyses
      the reduction of the monodehydroascorbate radical. To elucidate the evolution and
      functional role of MDHAR we identified and characterised MDHARs from the moss
      Physcomitrella patens. Expressed sequence tag (EST) databases containing
      approximately 100.000 ESTs from Physcomitrella were searched and three isoforms
      of monodehydroascorbate reductase (PpMDHAR1, PpMDHAR2 and PpMDHAR3) were
      identified. In vascular plants MDHAR is found in the cytosol, chloroplast,
      mitochondria and peroxisome. Surprisingly, all three PpMDHARs resembled the
      cytosolic isoforms from vascular plants lacking the NH(2)-terminal or COOH
      terminal extension found in organelle targeted MDHARs. The number and position of
      introns was also conserved between PpMDHARs and cytosolic MDHARs from vascular
      plants. Phylogenetic analysis revealed that cytosolic MDHARs are monophyletic in
      origin and the ancestral gene evolved before the divergence of bryophytes more
      than 400 million years ago. Transcript analyses showed that expression of
      PpMdhar1 and PpMdhar3 was increased up to 5-fold under salt stress, osmotic
      stress or upon exposure to abscisic acid. In contrast, PpMdhar transcription
      levels were unchanged upon chilling, UV-B exposure or oxidative stress. The
      conservation of cytosolic MDHAR in the land-plant lineage and the transcriptional
      upregulation under water deficiency suggest that the evolution of cytosolic MDHAR
      played an essential role in stress protection for land plants when they inhabited
      the dry terrestrial environment.

PMID- 16429264
TI  - Natural synchronisation for the study of cell division in the green unicellular
      alga Ostreococcus tauri.
AB  - Ostreococcus tauri (Prasinophyceae) is a marine unicellular green alga which
      diverged early in the green lineage. The interest of O. tauri as a potential
      model to study plant cell division is based on its key phylogenetic position, its
      simple binary division, a very simple cellular organisation and now the
      availability of the full genome sequence. In addition O. tauri has a minimal yet
      complete set of cell cycle control genes. Here we show that division can be
      naturally synchronised by light/dark cycles and that organelles divide before the
      nucleus. This natural synchronisation, although being only partial, enables the
      study of the expression of CDKs throughout the cell cycle. The expression
      patterns of OtCDKA and OtCDKB were determined both at the mRNA and protein
      levels. The single OtCDKA gene is constantly expressed throughout the cell cycle,
      whereas OtCDKB is highly regulated and expressed only in S/G2/M phases. More
      surprisingly, OtCDKA is not phosphorylated at the tyrosine residue, in contrast
      to OtCDKB which is strongly phosphorylated during cell division. OtCDKA kinase
      activity appears before the S phase, indicating a possible role of this protein
      in the G1/S transition. OtCDKB kinase activity occurs later than OtCDKA, and its
      tyrosine phosphorylation is correlated to G2/M, suggesting a possible control of
      the mitotic activity. To our knowledge this is the first organism in the green
      lineage which showed CDKB tyrosine phosphorylation during cell cycle progression.

PMID- 16429266
TI  - Risky anatomic variations of sphenoid sinus for surgery.
AB  - We searched for the surgically risky anatomic variations of sphenoid sinus and
      aimed to compare axial and coronal tomography in detection of these variations.
      Fifty-six paranasal tomography images (112 sides) were evaluated for coronal,
      axial and both coronal and axial images. Tomographic findings including bony
      septum extending to optic canal or internal carotid artery; protrusions and
      dehiscences of the walls of internal carotid artery, optic nerve, maxillary nerve
      and vidian nerve; extreme medial course of internal carotid artery; patterns of
      aeration of the anterior clinoid process; and Onodi cells were evaluated. The
      results were classified as "present, absent, suspicious-thin (only for
      dehiscence) or no-consensus". The results of each plane were compared with that
      of the result of the both planes together. Kappa coefficient and Chi-square tests
      were used to compare both planes. Twelve cadaveric dissections were performed to
      reveal the proximity of sphenoid sinus to surgically risky anatomic structures.
      Endoscopy was applied to five cadavers. 18 evaluations were classified as 'no
      consensus'. We detected 34, 35, 34 and 40 protrusions of internal carotid artery,
      optic nerve, maxillary nerve, vidian nerve, respectively. Dehiscences were
      present in 6, 9, 4 and 8, and suspicious-thin in 8, 10, 16 and 25 in canals of
      internal carotid artery, optic nerve, maxillary nerve and vidian nerve,
      respectively. Bony septum to internal carotid artery and optic nerve was observed
      in 30 and 22 cases. We observed 9 extreme medial courses of internal carotid
      artery, 27 aerated clinoid process and 9 Onodi cells. Axial images were superior
      in detection of bony septum to internal carotid artery and Onodi cells; while the
      coronal images were more successful in detection of protrusion of optic nerve and
      vidian nerve, and dehiscense of maxillary nerve and vidian nerve (P<0.05). In
      cadaveric dissections, the septa were inserted into the bony covering of the
      carotid arteries in two sinuses (8.3%). Detailed preoperative analysis of the
      anatomy of the sphenoid sinus and its boundaries is crucial in facilitating entry
      to the pituitary fossa and reducing intraoperative complications. Coronal
      tomography more successfully detects the sphenoid sinus anatomic variations.

PMID- 16429265
TI  - Genome-wide analysis and experimentation of plant serine/ threonine/tyrosine
      specific protein kinases.
AB  - Protein tyrosine phosphorylation plays an important role in cell growth,
      development and oncogenesis. No classical protein tyrosine kinase has hitherto
      been cloned from plants. Does protein tyrosine kinase exist in plants? To address
      this, we have performed a genomic survey of protein tyrosine kinase motifs in
      plants using the delineated tyrosine phosphorylation motifs from the animal
      system. The Arabidopsis thaliana genome encodes 57 different protein kinases that
      have tyrosine kinase motifs. Animal non-receptor tyrosine kinases, SRC, ABL, LYN,
      FES, SEK, KIN and RAS have structural relationship with putative plant tyrosine
      kinases. In an extended analysis, animal receptor and non-receptor kinases, Raf
      and Ras kinases, mixed lineage kinases and plant serine/threonine/tyrosine (STY)
      protein kinases, form a well-supported group sharing a common origin within the
      superfamily of STY kinases. We report that plants lack bona fide tyrosine
      kinases, which raise an intriguing possibility that tyrosine phosphorylation is
      carried out by dual-specificity STY protein kinases in plants. The distribution
      pattern of STY protein kinase families on Arabidopsis chromosomes indicates that
      this gene family is partly a consequence of duplication and reshuffling of the
      Arabidopsis genome and of the generation of tandem repeats. Genome-wide analysis
      is supported by the functional expression and characterization of At2g24360 and
      phosphoproteomics of Arabidopsis. Evidence for tyrosine phosphorylated proteins
      is provided by alkaline hydrolysis, anti-phosphotyrosine immunoblotting,
      phosphoamino acid analysis and peptide mass fingerprinting. These results report
      the first comprehensive survey of genome-wide and tyrosine phosphoproteome
      analysis of plant STY protein kinases.

PMID- 16429267
TI  - Deep femoral artery with four variations: a case report.
AB  - During our routine dissection course for students we found a complex variation of
      the femoral artery on the left side of a 72-year-old male cadaver. The deep
      femoral artery was originating from the anterior aspect of the femoral artery;
      the inferior epigastric and the external pudendal arteries were arising from the
      deep femoral artery. Besides, the lateral circumflex femoral artery was arising
      from the lateral aspect of the femoral artery and distal to the origin of the
      deep femoral artery.

PMID- 16429269
TI  - A multiphasic role for Pax7 in tectal development.
AB  - The optic tectum differentiates from the mesencephalic alar plate and matures
      into a characteristically laminated structure. Evidence presented here suggests a
      role for Pax7 in all stages of development of tectal architecture, from
      regionalisation to specification of neurons and tectal topography. Analysis of
      Pax7 expression profiles over a range of developmental stages (E2-E12) suggests a
      biphasic role for Pax7: initially Pax7 expressing cells in the proliferative
      neuroepithelial layer establish tectal polarity whereas later Pax7 is expressed
      in neurons of the retino-recipient precursor stratum griseum et fibrosum
      superficiale (sgfs) laminae where graded levels may establish tectal topography.
      Furthermore, co-localisation immunofluorescence confirmed that Pax7 is initially
      expressed in the majority of proliferative neuroepithelial cells and later in a
      subset of neurons of the sgfs laminae.

PMID- 16429268
TI  - Balancing bilateral sensory activity: callosal processing modulates sensory
      transmission through the contralateral thalamus by altering the response
      threshold.
AB  - Rats tactually explore a nearly spherical space field around their heads with
      their whiskers. The information sampled by the two sets of whiskers is integrated
      bilaterally at the cortical level in an activity dependent manner via the corpus
      callosum. We have recently shown that sensory activity in one barrel field cortex
      (BFC) modulates the processing of incoming sensory information to the other BFC.
      Whether interhemispheric integration is dynamically linked with corticothalamic
      modulation of incoming sensory activity is an important hypothesis to test, since
      subcortical relay neurons are directly modulated by cortical neurons through top
      down processes. In the present study, we compared the direct sensory responses of
      single thalamic relay neurons under urethane anesthesia before and after
      inactivating the BFC contralateral to a thalamic neuron. The data show that
      silencing one BFC reduces response magnitude in contralateral thalamic relay
      neurons, significantly and reversibly, in response to test stimuli applied to the
      principal whisker at two times response threshold (2T) intensity for each unit.
      Neurons in the ventral posterior medial (VPM) nucleus and the medial division of
      the posterior nucleus (POm) react in a similar manner, although POm neurons are
      more profoundly depressed by inactivation of the contralateral BFC than VPM
      neurons. The results support the novel idea that the subcortical relay of sensory
      information to one hemisphere is strongly modulated by activity levels in the
      contralateral as well as in the ipsilateral SI cortex. The mechanism of the
      modulation appears to be based on shifting the stimulus-response curves of
      thalamic neurons, thereby rendering them more or less sensitive to sensory
      stimuli. We conclude that global sensory processing is created by combining
      activity in each cerebral hemisphere and continually balancing the flow of
      information to cortex by adjusting the responsiveness of ascending sensory
      pathways.

PMID- 16429271
TI  - Magnetic resonance imaging after radiofrequency ablation in a rodent model of
      liver tumor: tissue characterization using a novel necrosis-avid contrast agent.
AB  - We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging
      (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing
      liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I,
      complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h
      after RFA, T1-weighted (T1-w) MRI was performed before and after injection of
      ECIV-7 at 0.05 mmol/kg and followed up from 6-24 h. Signal intensities (SIs) were
      measured with relative enhancement (RE) and contrast ratio (CR) calculated. The
      MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts
      between normal liver, RFA lesion, residual and/or intact tumor were vague. Early
      after administration of ECIV-7, the liver SI was strongly enhanced (RE=40-50%),
      leaving the RFA lesion as a hypointense region in groups I and II. At delayed
      phase, two striking peri-ablational enhancement patterns appeared (RE=90% and
      CR=1.89%), i.e., "O" type of hyperintense rim in group I and "C" type of
      incomplete rim in group II. These MRI manifestations could be proven
      histologically. In this study, tissue components after RFA could be characterized
      with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI,
      especially at delayed phase. This approach may prove useful for defining the
      ablated area and identifying residual tumor after RFA.

PMID- 16429270
TI  - Suppression of cutaneous reflexes by a conditioning pulse during human walking.
AB  - There are two ways in which responses to successive unexpected stimuli are
      attenuated, namely through habituation and conditioning. For the latter, it
      suffices that the unexpected stimulus is preceded by another just perceivable
      stimulus. In spinal cord reflexes this is termed conditioning, while in brainstem
      reflexes this is usually referred to as prepulse inhibition. Cutaneous reflexes
      in Tibialis Anterior (TA) are particularly strong during gait and they are
      thought to involve a transcortical loop. Can these reflexes be suppressed by
      giving a brief pulse prior to a reflex-evoking pulse given to the same nerve? To
      examine this question, electromyographic signals were recorded in healthy humans
      during walking. Sural nerve stimulation (train of five pulses (1 ms duration)) at
      200 Hz were applied at two times perception threshold during different phases of
      the step cycle. The preceding pulse (single pulse of 1 ms at same intensity) was
      applied to the same nerve 150 ms before the reflex-evoking pulse train.
      Conditioning stimulation with a single pulse lowered significantly the following
      reflex response in the ipsilateral TA but much less in other muscles such as
      biceps femoris. The preceding pulse did not disturb the phase-dependent
      modulation or the typical reflex reversal. The finding that TA is selectively
      involved indicates that the suppressing mechanism may involve the motor cortex,
      which is known to be involved in the control of TA. The conditioning pulse did
      not cause a reduction in background activity. Therefore, the suppression of the
      reflex responses points to a premotoneuronal source such as presynaptic
      inhibition.

PMID- 16429272
TI  - Safety of iobitridol in the general population and at-risk patients.
AB  - The purpose of this study was to review the rate of adverse events after contrast
      medium administration in the general population and at-risk patients (renal
      impairment, heart failure (NYHA III or IV), hypotension or hypertension, coronary
      artery disease, previous reaction to contrast media, asthma and/or allergies,
      dehydration, diabetes mellitus, poor general condition) under daily practice
      conditions in a post-marketing surveillance study. Two hundred and ten
      radiologists conducted various X-ray examinations in 52,057 patients. To document
      the safety of iobitridol in routine use, all patients undergoing X-ray
      examinations were included. Exclusion criteria were contraindications listed in
      the locally approved summary of product characteristics. The adverse event rate
      was 0.96% (at-risk patients 1.39%); the rate of serious adverse events 0.044% in
      all patients (at-risk patients 0.057%). Adverse events occurred more often in
      women than in men (P < 0.001). In patients who had previously reacted to a
      contrast medium, adverse events were reported in 3.43% with mild to moderate
      symptoms. In 47.76% of these patients, a premedication was administered. There
      was no difference in the frequency of adverse events and serious adverse events
      whether premedicated or not (P = 0.311 and P = 0.295, respectively). Iobitridol
      was well-tolerated in 99.04% of cases (at-risk patients 98.61%).

PMID- 16429273
TI  - Idiopathic infantile arterial calcification: imaging evaluation and the
      usefulness of MR angiography.
AB  - Idiopathic infantile arterial calcification (IIAC) is a rare condition
      characterized by extensive calcification and stenosis of large and medium-size
      arteries. The etiology of the disease is unknown. However, the inheritance
      pattern has been shown to be autosomal recessive. The clinical presentation is
      variable, including cardiac failure (most common clinical finding), hypertension,
      and respiratory failure. Plain radiography, sonography and MRI can aid in the
      diagnosis. We present a case in which contrast-enhanced MR angiography with
      breath-hold and cardiac gating techniques allowed complete evaluation of the
      extent of this disease.

PMID- 16429274
TI  - Mitotic activity of Sertoli cells in adult human testis: an immunohistochemical
      study to characterize Sertoli cells in testicular cords from patients showing
      testicular dysgenesis syndrome.
AB  - During puberty, normal somatic Sertoli cells undergo dramatic morphological
      changes due to the differentiation of immature pre-Sertoli cells in functionally
      active adult Sertoli cells. Sertoli cell maturation is accompanied with loss of
      their mitotic activity before onset of spermatogenesis and loss of pre-pubertal
      and occurrence of adult immunohistochemical Sertoli cell differentiation markers.
      Testes of infertile adult patients often exhibit numerous histological signs of
      testicular dysgenesis syndrome (TDS) such as microliths, Sertoli cell only (SCO)
      tubules, tubules containing carcinoma in situ and immature seminiferous tubules
      (Sertoli cell nodules). Sertoli cell tumours, however, are very rare neoplasms
      possibly due to the fact that the mechanism and temporal origin of neoplastic
      Sertoli cells underlying Sertoli cell tumourigenesis still remain unknown. To
      clarify the state of Sertoli cell differentiation in both immature seminiferous
      tubules of adult patients with TDS and Sertoli cell tumour, we compared the
      expression of the Sertoli cell differentiation markers vimentin, inhibin-alpha,
      anti-Muellerian-hormone, cytokeratin 18, M2A-antigen, androgen receptor and
      connexin43 with that of SCO tubules with hyperplasia. In addition, we
      demonstrated for the first time the existence of proliferating Sertoli cells by
      Ki67- and PCNA-immunostaining in Sertoli cell nodules of the adult human testis.
      Our data indicate that mitotically active Sertoli cells in Sertoli cell nodules
      will be arrested prior to puberty and, contrary to dogma, do not represent foetal
      or neonatal cells. Since all markers in Sertoli cell nodules revealed a staining
      pattern identical to that in neoplastic Sertoli cells, but different to that in
      Sertoli cells of SCO tubules with hyperplasia, it may be speculated that Sertoli
      cell tumours in adult men may originate from Sertoli cell nodules.

PMID- 16429275
TI  - Homocysteine, hRIP3 and congenital cardiovascular malformations.
AB  - Elevated serum homocysteine (Hcys) levels have been suggested to contribute to
      congenital cardiovascular malformations, neural tube defects, and cardiovascular
      diseases. To investigate the mechanisms resulting in cardiovascular diseases and
      birth defects, Kuang-Hueih Chen et al. identified and characterized a novel gene,
      named rHCY2, whose expression was markedly up-regulated when Hcys was elevated in
      rat. In vivo, rHCY2 gene could induce chicken embryonic cells apoptosis and
      embryonic malformations. Its N-terminal kinase domain is apparently similar to
      human receptor-interacting serine-threonine kinase 3 (hRIP3). In view of this, we
      hypothesize that a link between the teratogenic effects of Hcys and hRIP3 is
      theoretically plausible. However, given the lack of data on the topic, it remains
      to be seen whether an elevated serum Hcys level will increase the expression of
      hRIP3. Using normal and abnormal human fetal hearts and cultured normal human
      fetal cardiomyocytes, we show that congenital cardiovascular malformations are
      associated with the overexpression of hRIP3, and evidence is found for a certain
      association between overexpression of hRIP3 and homocysteine-induced congenital
      cardiovascular malformations. Folic acid and anti-hRIP3 antibodies seem to favor
      maintenance of the shape and ultrastructure of cultured human fetal
      cardiomyocytes.

PMID- 16429276
TI  - High-resolution episcopic microscopy: a rapid technique for high detailed 3D
      analysis of gene activity in the context of tissue architecture and morphology.
AB  - We describe a new methodology for rapid 2D and 3D computer analysis and
      visualisation of gene expression and gene product pattern in the context of
      anatomy and tissue architecture. It is based on episcopic imaging of embryos and
      tissue samples, as they are physically sectioned, thereby producing inherently
      aligned digital image series and volume data sets, which immediately permit the
      generation of 3D computer representations. The technique uses resin as embedding
      medium, eosin for unspecific tissue staining, and colour reactions (beta
      galactosidase/Xgal or BCIP/NBT) for specific labelling of gene activity and mRNA
      pattern. We tested the potential of the method for producing high-resolution
      volume data sets of adult human and porcine tissue samples and of specifically
      and unspecifically stained mouse, chick, quail, frog, and zebrafish embryos. The
      quality of the episcopic images resembles the quality of digital images of true
      histological sections with respect to resolution and contrast. Specifically
      labelled structures can be extracted using simple thresholding algorithms. Thus,
      the method is capable of quickly and precisely detecting molecular signals
      simultaneously with anatomical details and tissue architecture. It has no tissue
      restrictions and can be applied for analysis of human tissue samples as well as
      for analysis of all developmental stages of embryos of a wide variety of
      biomedically relevant species.

PMID- 16429277
TI  - Clinical manifestations and neurodevelopmental outcome following an event of
      accidental intramuscular injection of atracurium in newborns.
AB  - Pediatric populations are at risk for medication errors that may be associated
      with mortality and disability. The purpose of this study was to describe the
      clinical manifestations of seven newborns following an event of accidental
      intramuscular injection of atracurium and to assess the impact on
      neurodevelopmental outcome. This study enrolled seven newborns who were
      accidentally administered 10 mg of atracurium, equivalent to 2.6-3.3 mg/kg, in a
      local perinatal clinic. Accident reports and hospital records were reviewed to
      obtain the history and medical data for the event. The survivors were
      prospectively examined for their growth, health and neurodevelopment until 24
      months of age. All newborns showed immediate apnea and cyanosis requiring
      resuscitation after atracurium injection and presented with respiratory failure
      and flaccid paralysis on arrival for emergency medical services. One newborn was
      asystolic despite resuscitation and died of multiple organ failure. Of the five
      survivors available for follow-up, all achieved favorable growth outcomes.
      However, four showed mild to significant delay in development; and two manifested
      mild hypomyelination of cerebral white matter on the brain magnetic resonance
      imaging. CONCLUSION: Newborns accidentally injected with high doses of atracurium
      are at risk of death and neurodevelopmental delay. The serious clinical
      manifestations, developmental delay and cerebral hypomyelination were most likely
      due to insufficient immediate respiratory assistance following atracurium
      injection.

PMID- 16429278
TI  - Onset of acquired autoimmune hypothyroidism in infancy: a presentation of delayed
      gross-motor development and rhabdomyolysis.
AB  - We report the case of a 23-month-old girl who presented with poor growth and
      delayed attainment of gross-motor milestones. Elevated creatine phosphokinase
      (CPK) indicated rhabdomyolysis, ultimately attributed to severe, acquired
      autoimmune hypothyroidism. Growth data and bone-age suggest the onset of
      hypothyroidism occurred at or before 12 months of age. Acquired hypothyroidism is
      rare before age 3 years, and rhabdomyolysis due to hypothyroidism has not
      previously been reported as a cause of delayed gross-motor development in
      toddlerhood. Despite the early onset of hypothyroidism, cognitive function
      appeared to be unaffected. Adequate thyroid hormone replacement quickly
      normalized the CPK in our patient, and gross motor development rapidly improved.
      Although rare, rhabdomyolysis secondary to hypothyroidism should be in the
      differential diagnosis of delayed gross-motor development in infancy and
      toddlerhood.

PMID- 16429279
TI  - Measurements of fast neutrons in Hiroshima by use of (39)Ar.
AB  - The survivors of the A-bomb explosions over Hiroshima and Nagasaki were exposed
      to a mixed neutron and gamma radiation field. To validate the high-energy portion
      of the neutron field and thus the neutron dose to the survivors, a method is
      described that allows retrospective assessment of the fast neutrons from the A
      bombs. This is accomplished by the extraction of the noble gas argon from
      biotites separated from Hiroshima granite samples, and then the detection of the
      (39)Ar activity that was produced by the capture of the fast neutrons on
      potassium. Adjusted to the year 1945, activities measured in the first samples
      taken at distances of 94, 818, 992, and 1,173 m from the hypocenter were 6.9+/
      0.2, 0.32+/-0.01, 0.14+/-0.02, and 0.09+/-0.01 mBq/g K, respectively. All signals
      were significantly above detector background and show low uncertainties.
      Considering their uncertainties they agree with the calculated (39)Ar activation
      in the samples, based on the most recent dosimetry system DS02. It is concluded
      that this method can be used to investigate samples obtained from large distances
      in Hiroshima, where previous data on fast neutrons are characterized by
      considerable uncertainties. Additionally, the method can be used to reconstruct
      the fast neutron fluence in Nagasaki, where no experimental data exist.

PMID- 16429280
TI  - Gene cloning, expression and functional characterization of an acyl carrier
      protein AcpV from Vibrio anguillarum.
AB  - Acyl carrier protein (ACP) is a small acidic protein that acts as an essential
      cofactor in many biosynthetic pathways depending on acyl transfer reactions. In
      this work, a Vibrio anguillarum ACP encoding gene, acpV, was first cloned from
      the chromosome of a virulent V. anguillarum strain MVM425. acpV was over
      expressed in Escherichia coli and the resultant protein AcpV was purified. The
      purified AcpV was incubated with purified phosphopantetheinyl transferase
      (PPtase) in the presence of CoA to assay the 4'-phosphopantetheinylation of AcpV
      in vitro; and on the other hand, the acpV gene was co-expressed with PPtase
      encoding gene in E. coli to examine the 4'-phosphopantetheinylation of AcpV in
      vivo. Our results suggested that acpV encoded a functional ACP of V. anguillarum,
      which can be 4'-phosphopantetheinylated well by AcpS-type PPtase (E. coli AcpS)
      both in vitro and in vivo, but cannot serve as a good substrate for Sfp-type
      PPtase (V. anguillarum AngD).

PMID- 16429281
TI  - Dural arteriovenous fistula of the lesser sphenoid wing region treated with Onyx:
      technical note.
AB  - A 45-year-old man presented with acute right orbital pain and right-sided
      headache. Magnetic resonance imaging (MRI) and cerebral angiography revealed a
      dural arteriovenous fistula (DAVF) of the lesser sphenoid wing region. The lesion
      was endovascularly treated by transarterial embolization with Onyx (ethyl vinyl
      alcohol; Micro Therapeutics, Irvine, Calif.). We review some anatomical and
      therapeutic features involving DAVFs of this region and describe the feasibility
      of the use of Onyx in the treatment of these lesions.

PMID- 16429282
TI  - Recombinant production of fibrinogenase IV from Agkistrodon acutus venom and its
      preliminary evaluation.
AB  - A novel metalloproteinase, recombinant fibrinogenase IV (rFIVa), was expressed
      and purified from Agkistrodon acutus venom. It is a single-chain protein with an
      apparent molecular weight of 27 kDa. Western blot showed that it had a good
      immunological reaction against anti-FIVa rabbit serum. The kinetic parameters Km
      and Kcat of rFIVa on the substrate T6140 were 7.471 x 10(-4) mol/l and 5.103 x
      10(-5) s(-1). RFIVa cleaved preferentially the alpha-chain, and the beta- and
      gamma-chains of fibrinogen were also cleaved when the incubation time was
      prolonged. The administration of rFIVa (1.8 and 5.4 mg/kg) to animals with acute
      blood-stasis model produced a decrease in fibrinogen to control values. To our
      knowledge, this is the first report of the expression, purification, and
      evaluation of recombinant fibrinogenase IV, which belongs to class P-I
      metalloproteinase from A. acutus venom.

PMID- 16429283
TI  - Rasterstereographic analysis of axial back surface rotation in standing versus
      forward bending posture in idiopathic scoliosis.
AB  - The forward bending test according to Adams and rib hump quantification by
      scoliometer are common clinical examination techniques in idiopathic scoliosis,
      although precise data about the change of axial surface rotation in forward
      bending posture are not available. In a pilot study the influence of leg length
      inequalities on the back shape of five normal subjects was clarified. Then 91
      patients with idiopathic scoliosis with Cobb-angles between 20 degrees and 82
      degrees were examined by rasterstereography, a 3D back surface analysis system.
      The axial back surface rotation in standing posture was compared with that in
      forward bending posture and additionally with a scoliometer measurement in
      forward bending posture. The changes of back shape in forward bending posture
      were correlated with the Cobb-angle, the level of the apex of the scoliotic
      primary curve and the age of the patient. Averaged over all patients, the back
      surface rotation amplitude increased from 23.1 degrees in standing to 26.3
      degrees in forward bending posture. The standard deviation of this difference was
      high (6.1 degrees ). The correlation of back surface rotation amplitude in
      standing with that in forward bending posture was poor (R (2)=0.41) as was the
      correlation of back surface rotation in standing posture with the scoliometer in
      forward bending posture measured rotation (R (2)=0.35). No significant
      correlation could be found between the change of back shape in forward bending
      and the degree of deformity (R (2)=0.07), likewise no correlation with the height
      of the apex of the scoliosis (R (2)=0.005) and the age of the patient (R
      (2)=0.001). Before forward bending test leg length inequalities have to be
      compensated accurately. Compared to the standing posture, forward bending changes
      back surface rotation. However, this change varies greatly between patients, and
      is independent of the type and degree of scoliosis. Furthermore remarkable
      differences were found between scoliometer measurement of the rib hump and
      rasterstereographic measurement of the vertebral rotation. Therefore the forward
      bending test and the identification of idiopathic scoliosis rotation by
      scoliometer can be markedly different compared to rasterstereographic surface
      measurement in the standing posture.

PMID- 16429284
TI  - Mycoplasma hominis deep wound infection after neuromuscular scoliosis surgery:
      the use of real-time polymerase chain reaction (PCR).
AB  - Mycoplasma hominis is a commensal of the genitourinary tract. It mostly causes
      infections to associated structures of this system; however, occasionally it is a
      pathogen in nongenitourinary tract infections. Since, M. hominis strains require
      special growth conditions and cannot be Gram stained, they may be missed or delay
      diagnosis. This report describes a deep wound infection caused by M. hominis
      after neuromuscular scoliosis surgery; M. hominis was recovered by real-time
      polymerase chain reaction (PCR). An awareness of the role of M. hominis as an
      extragenital pathogen in musculoskeletal infections, especially in neuromuscular
      scoliosis, being a high-risk group for postoperative wound infection, it is
      necessary to identify this pathogen. Real-time PCR for postoperative deep wound
      infection, in patients with a history of genitourinary infections, decreases the
      delay in diagnosis and treatment. In these cases rapid real-time PCR on deep
      cultures should be considered.

PMID- 16429286
TI  - Surgical treatment of high-grade lumbosacral spondylolisthesis in childhood,
      adolescent and young adult by the "double-plate" technique: a past experience.
AB  - Between 1979 and 1996, 40 patients with high-grade lumbosacral spondylolisthesis
      were treated in our institution using a newly designed osteosynthesis device. The
      mean age was 13 years and 6 months, and the mean follow-up was 18 years. Combined
      posterior decompression and anterior reduction, instrumentation and fusion of the
      slippage were performed in all cases. The technique includes reduction of the
      slippage by means of an anteriorly placed plate that engages two screws,
      previously placed during the posterior approach, going through the S1 vertebra.
      Progressive compression applied on the plate by the screws achieves reduction.
      Complete fusion was obtained in all 40 patients. Twelve patients presented a
      postoperative radiculopathy, from which only ten recovered completely. There were
      six L4-L5 annulus lesions, responsible for instability, produced by the plate. We
      report five late infections. Thirty-five of the forty patients were asymptomatic
      at the latest follow-up. The double compressive plate technique proved to be
      effective in obtaining lumbosacral fusion and optimal slippage reduction.
      However, the high rates of neurological and infectious complications preclude
      recommendation of this technique in its present form.

PMID- 16429285
TI  - Clinical, radiological and histological study of the failure of cervical
      interbody fusions with bone substitutes.
AB  - Few histological studies on bone substitutes in human cervical spine are
      available and the biological processes of bone substitutes are not well
      documented. The authors studied four failure cases of cervical interbody fusion:
      two cases with hydroxyapatite (HA), one case with beta-tricalcium phosphate
      ceramic (beta-TCP) and one case with xenograft (bovine bone). Clinical data
      showed that all the patients experienced neck pain with or without numbness of
      upper extremity due to fusion failure. Successful fusions were achieved after the
      salvage surgeries in which autograft were used. Radiographs showed that
      radiolucent lines were present in all cases. Two HA substitutes fractured without
      complications. One of them sank into the vertebral body. Some small beta-TCP
      fragments were found under the microscope. Histological study demonstrated only a
      few newly formed bones at the interface of the substitutes. The fragments of HA
      were encapsulated by fibrous tissue. The degradation process and bone
      regeneration were more active in beta-TCP than in HA. The intertrabecular spaces
      of bovine bone were filled with fibrous tissue. The results suggest that a porous
      calcium phosphate ceramic with special design might assure bone ingrowth and meet
      the mechanical requirements in cervical interbody fusion. The complications of
      these materials in the cervical spine should be highlighted.

PMID- 16429287
TI  - Effectiveness of the Providence nighttime bracing in adolescent idiopathic
      scoliosis: a comparative study of 36 female patients.
AB  - The aim of the study was to assess the results of treatment of adolescent
      idiopathic scoliosis (AIS) with the Providence nighttime brace at 1.8 years after
      discontinuation of bracing. A total of 36 consecutive female patients with an
      average Cobb angle of 28.4 degrees and an apex below T 10 were studied
      prospectively. For comparisons, 36 matched patients treated with the Boston full
      time brace were studied retrospectively. With the Providence night brace an
      average of 92% for brace correction of the primary curve was achieved and during
      follow-up progression of the curve >5 degrees occurred in 27% of the patients. In
      the control group of the Boston full-time brace patients, brace correction was
      50% and the progression of the major curve occurred in 22% of the patients. We
      conclude that the Providence night brace may be recommended for the treatment of
      AIS with curves less than 35 degrees in lumbar and thoracolumbar cases.

PMID- 16429288
TI  - Efficacy and safety of balloon kyphoplasty in the treatment of vertebral
      compression fractures: a systematic review.
AB  - The aim of this study is to evaluate the efficacy and safety of balloon
      kyphoplasty (BK) in the management of vertebral compression fractures (VCFs).
      This study is based on a systematic review of the literature (until October 2004)
      and meta-analysis of clinical studies assessing the efficacy and safety of BK in
      the treatment of VCFs. Estimates of effect were based on a random effects model.
      Meta-regression analyses were carried out where required. A total of 26 studies
      met the inclusion criteria. Although studies displayed considerable
      methodological limitations, the results of the clinical series indicate
      significant improvements in pain intensity, vertebral height, sagittal alignment,
      functional capacity, and quality of life. Compared with conventional medical
      management, BK afforded significant improvement in pain intensity and mobility.
      Likewise, a significant reduction was observed in vertebral collapse, kyphotic
      deformity, the development of new vertebral fractures, and hospital stay.
      Compared with vertebroplasty, the technique reduced the loss of height and the
      degree of kyphotic deformity, and afforded a significantly lower leakage rate
      with no differences in relation to other variables. Regarding adverse effects,
      leakage affected 7% of all levels treated, while complications were recorded in
      2% of the patients, and new vertebral fractures in 16%. The available evidence
      suggests that BK can be effective and safe in application to VCFs. However,
      existing studies evince substantial methodological limitations and relatively
      short follow-up periods. Better clinical research is required to determine the
      capacity of BK to avoid the functional and physiological sequelae of VCFs and to
      define the true role of the technique among the existing therapeutic options.

PMID- 16429289
TI  - Comparison of the biomechanical stability of dense cancellous allograft with
      tricortical iliac autograft and fibular allograft for cervical interbody fusion.
AB  - Several choices are available for cervical interbody fusion after anterior
      cervical discectomy. A recent option is dense cancellous allograft (CS) which is
      characterized by an open-matrix structure that may promote vascularization and
      cellular penetration during early osseous integration. However, the biomechanical
      stability of CS should be comparable to that of the tricortical iliac autograft
      (AG) and fibular allograft (FA) to be an acceptable alternative to these
      materials. The purpose of this study was to compare the initial biomechanical
      stability of CS to that of AG and FA in a one-level anterior cervical discectomy
      and interbody fusion (ACDF) model. Twelve human cervical spines (C3-T1) were
      loaded in six modes of motion and evaluated under three conditions: (1) intact,
      (2) after ACDF using CS, AG, and FA in alternating sequences, and (3) after ACDF
      with anterior plating. Three reflective markers were placed on the adjacent
      vertebral bodies. Intervertebral motion was measured with a video-based motion
      capture system (MacReflex, Qualisys, Sweden). Torques were applied to a maximum
      of 2.0 N m. The range-of-motion and neutral-zone values measured in each loading
      mode were compared. No graft material displayed significant differences in
      biomechanical stability in any of the tested loading modes, suggesting that the
      initial stability of CS is comparable to that of AG and FA. Anterior cervical
      plating significantly increased biomechanical stability in all modes.

PMID- 16429290
TI  - Candida albicans osteomyelitis of the spine: progressive clinical and
      radiological features and surgical management in three cases.
AB  - Candida albicans vertebral osteomyelitis is rare. Three cases are presented.
      Without antifungal treatment, they developed spinal collapse and neurological
      deterioration within 3-6 months from the onset of symptoms. There was a delay of
      4.5 and 7.5 months between the onset of symptoms and surgery. All patients were
      managed with surgical debridement and reconstruction and 12-week fluconazole
      treatment. The neurological deficits resolved completely. The infection has not
      recurred clinically or radiologically at 5-6 years follow-up. Although rare,
      Candida should be suspected as a causative pathogen in cases of spinal
      osteomyelitis. Without treatment the disease is progressive. As soon as
      osteomyelitis is suspected, investigations with MRI and percutaneous biopsy
      should be performed followed by medical therapy. This may prevent the need for
      surgery. However, if vertebral collapse and spinal cord compression occurs,
      surgical debridement, fusion and stabilisation combined with antifungal
      medications can successfully eradicate the infection and resolve the neurological
      deficits.

PMID- 16429291
TI  - Influence of a dynamic stabilisation system on load bearing of a bridged disc: an
      in vitro study of intradiscal pressure.
AB  - In recent years, non-fusion implants to stabilise the lumbar spine have become
      more and more popular. However, little is known on the load bearing of such
      dynamic stabilisation systems. In order to investigate the load bearing of discs
      bridged with rigid and dynamic stabilisation systems, six lumbar cadaver spines
      were mounted in a spine tester and loaded with pure moments in the three main
      motion planes. Four different states of the specimens were studied: intact,
      destabilised, stabilisation with a Dynesys and stabilisation with an internal
      fixator. Intradiscal pressure (IDP) measurements were used to assess the load
      bearing of the bridged disc. In the neutral unloaded position, there were small
      but not significant differences in disc pressure for the four states of the
      treated disc (P>0.05). Concerning the disc pressure during the course of loading,
      both the Dynesys and internal fixator did significantly reduce the pressure
      change from neutral to extension in comparison to the intact state (-0.05, -0.04
      and +0.24 MPa, respectively) (P<0.05). Compared to the intact state, there was no
      significant pressure change from neutral to flexion (0.14, 0.15 and 0.18 MPa,
      respectively) (P>0.05). The devices apparently eliminated the pressure change
      from neutral to lateral bending (Dynesys 0.01 MPa, Fixator 0.01 MPa and intact
      0.24 MPa), but due to large variations in the intact and defect states the
      differences were not significant (P>0.05). In axial rotation, the pressure change
      for the internal fixator was reduced compared to the intact state; however, the
      change was only significant in left axial rotation (P<0.05). The Dynesys showed
      no significant differences (P>0.05) in axial rotation. No changes in IDP were
      seen in the adjacent discs for either the Dynesys or the internal fixator. Our
      results showed that the IDPs for both devices were similar, but altered compared
      to the intact disc.

PMID- 16429293
TI  - In vivo study of the kinematics in axial rotation of the lumbar spine after total
      intervertebral disc replacement: long-term results: a 10-14 years follow up
      evaluation.
AB  - INTRODUCTION: We did not find any in vivo study of spinal segment kinematics
      after disc replacement, especially over the long term. In vitro studies did show
      that it restores almost normal kinematics except for axial rotation. The goal of
      this study is to develop a new technique in order to analyse axial rotation of a
      spinal segment, in vivo, after total disc replacement. MATERIALS AND METHODS: A
      comparative retrospective study of motion in axial rotation at L4L5 level was
      carried out on 17 patients with artificial discs versus six healthy volunteers.
      Five patients carried one prostheses at L4L5 level and 12 carried two prosthesis
      at L4L5 and L5S1 levels. The follow up ranged from 10.8 to 14.3 years (average
      12.4+/-1, median 12.6). Dynamic radiographs in axial rotation were made using a
      special protocol. A new technique associating a stereographic method and image
      processing software was developed in order to evaluate the range of motion in
      axial rotation as well as the mechanical coupling. RESULTS: The standard
      deviation of angular measurements was 1.8 degrees . Eleven (65%) patients had a
      normal mobility in torsion, identical to those of the volunteers and of the
      literature, whereas six (35%) had an abnormal increased mobility. If only one
      disc was replaced, mobility in torsion was identical to that of the volunteers,
      in the case of two replaced discs, 50% (6/12) of the patients had an abnormal
      increased mobility. In the sub-group of normal mobility, the coupling was
      identical to that of the volunteers. In the sub-group of increased mobility, the
      coupling was different with a strong flexion (10 degrees ), increased by about 7
      degrees (P<0.001). CONCLUSION: The implementation of only one discal prosthesis
      SB Charite seems to restore kinematics close to that of the healthy volunteers
      and comparable to the literature. The implementation of two adjacent prostheses
      does not restore normal kinematics in 50% of the cases. It is probable that the
      existence of active stabilizing elements explains the difference with the in
      vitro studies carried out beforehand.

PMID- 16429292
TI  - A rare case of complete C2-C3 dislocation with mild neurological symptoms.
AB  - The authors report a rare case of complete C2-C3 dislocation with unexpectedly
      mild neurological symptoms in a 57 year old man involved in a motor vehicle
      accident, who had previously undergone posterior laminectomy from C3 through C7.
      A retrospective chart analysis and a thorough radiographic review were performed.
      X-rays and CT of the cervical spine demonstrated a complete dislocation at the C2
      C3 level. Computed tomographic angiography revealed disruption of both vertebral
      arteries; however, blood flow was evident in the basilar artery. After
      radiologically guided placement in cervical traction with tongs that reduced the
      subluxation by approximately 50% the patient had spontaneous eye opening and was
      able to follow commands. A two-stage 360 degree stabilization and fusion was
      performed and the patient was finally discharged 24 days after admission with his
      neurological status essentially unchanged. In conclusion, our patient presented
      with surprisingly mild neurological symptoms. The previously performed
      laminectomy could have both predisposed to injury as well as protected his spinal
      cord from potentially fatal trauma.

PMID- 16429294
TI  - [Integrated approach to the promotion of young academics in vision research at a
      European level].
AB  - The European Commission predicts a dramatic dearth of researchers and doctors in
      the near future. At the same time, highly qualified and motivated human resources
      form the only guarantee for further development of scientific knowledge for
      research and clinical application. This situation calls for an integrated
      approach to the promotion of young academics in vision research at a European
      level. The Marie Curie Program of the European Union is an ideal tool, which can
      be used particularly efficiently in vision research to promote international
      networking and dedicated advancement of young academics. The exemplary chances
      and opportunities of this strategy can be demonstrated by six specific measures
      of the University Eye Hospital in Tubingen. In particular, strictly defined
      medical areas will need to fully exploit their innovation potential in the future
      in order to secure their position in the global research area or even to expand
      it. New organizational concepts and long-term career options as well as a clear
      commitment to cutting-edge performance are the prerequisites for effective
      promotion of young academics.

PMID- 16429295
TI  - The relationship between health care expenditure and health outcomes. Evidence
      and caveats for a causal link.
AB  - The relationship between health care expenditure and health outcomes is of
      interest to policy makers in the light of steady increases in health care
      spending for most industrialised countries. However, establishing causal
      relationships is complex because, firstly, health care expenditure is only one of
      many quantitative and qualitative factors that contribute to health outcomes,
      and, secondly, measurement of health status is an imperfect process. This study
      reviews key findings and methodological approaches in this field and reports the
      results of our own empirical study of countries of the European Union. Our
      analysis examines life expectancy and infant mortality as the 'output' of the
      health care system, and various life-style, environmental and occupational
      factors as 'inputs'. Econometric analyses using a fixed effects model are
      conducted on a panel data set for the former 15 members of the European Union
      over the period 1980-1995. The findings show that increases in health care
      expenditure are significantly associated with large improvements in infant
      mortality but only marginally in relation to life expectancy. The findings are
      generally consistent with those of several previous studies. Caveats and
      improvements for future research are presented.

PMID- 16429296
TI  - Cost-utility analysis comparing meropenem with imipenem plus cilastatin in the
      treatment of severe infections in intensive care.
AB  - This study compared the cost-effectiveness of meropenem with that of imipenem
      plus cilastatin in the treatment of severe infections in hospital intensive care
      in the UK. A Markov model was constructed to model lifetime costs and quality
      adjusted life years (QALYs) of using meropenem and imipenem plus cilastatin for
      the treatment of severe infections in intensive care. Estimates of effectiveness,
      utility weights and costs were obtained from the published literature.
      Probabilistic sensitivity analysis was conducted to assess the robustness of the
      results. Estimated treatment costs for the patient cohort were pound 14,938 with
      meropenem and pound 15,585 with imipenem plus cilastatin. QALYs gained were 7,495
      with meropenem and 7,413 with imipenem plus cilastatin. Probabilistic sensitivity
      analysis showed meropenem to be significantly less costly (-pound 636.47, 95% CI 
      pound 132.33 to -pound 1,140.62) and more effective (0.084, 95% CI 0.023 to
      0.144). Meropenem thus appears significantly more effective and less expensive
      than imipenem plus cilastatin and should therefore be considered the dominant
      treatment strategy.

PMID- 16429297
TI  - Parents' informational needs at the birth of a baby with a surgically correctable
      anomaly.
AB  - Previous studies have assessed informational needs of parents of sick fetuses,
      neonates and children to identify favourable patterns of physician-parent
      interaction. The aim of this paper was to assess parents' informational needs
      before and after the operation when the one affected by a surgically correctable
      anomaly is a newborn. In the period ranging from 1997 to 2000 all couples with
      newborns undergoing major surgical procedures at birth, at the Newborn Surgery
      Unit of the Hospital Bambino Gesu, were surveyed by means of a questionnaire.
      Thirty couples form the object of the study. The two genders did not show
      significant difference in any of the considered items. All 30/30 mothers (M;
      100%) and 29/30 fathers (F; 97%) had never heard about the anomaly before the
      diagnosis was established in their baby. All parents (100%) stated that it would
      be better if the surgeon informed them with written educational material.
      Principal informational needs before operation regard: the description of the
      anomaly (M = 10; F = 11) and the prognosis in terms of survival chances of the
      baby (M = 17; F = 15); after surgery the cause of the anomaly (M = 5; F = 3); the
      steps of the recovery process (M = 10; F = 12) as well as the quality of their
      baby's life (M = 9; F = 9). In the immediate perioperative period the surgeon
      should well address parents' informational needs, which may significantly differ
      from his communication plan.

PMID- 16429298
TI  - Apoptotic cell death in toxic epidermal necrolysis: the Fas ligand assumption.

PMID- 16429299
TI  - Effects of isotretinoin on the metabolism of triglyceride-rich lipoproteins and
      on the lipid profile in patients with acne.
AB  - Isotretinoin treatment alters the plasma lipid levels but the mechanisms and the
      effects on the metabolism of triglyceride-rich lipoproteins such as chylomicrons
      and very-low-density lipoproteins remain unclear. We investigated the effect of
      isotretinoin on the plasma kinetics of emulsion models of triglyceride-rich
      lipoproteins and the lipid profile. Ten patients with acne were treated with 0.8
      mg/kg of isotretinoin over 4 weeks for comparison with non-treated acne patients.
      In both groups the plasma kinetic study of a triglyceride-rich emulsion double
      labeled with 14C-cholesterol oleate and 3H-triolein was performed after
      intravenous injection of the emulsion and radioactive counting in plasma samples
      collected over 60 min. Patients using isotretinoin showed decreased removal from
      the plasma of the 3H-triglyceride (median 0.019 min-1 TG) compared with controls
      (median 0.044 min-1, P=0.007), and the removal of the emulsion 14C-cholesterol
      oleate also tended to be decreased (treatment: 0.011 min-1; controls: 0.024 min
      1, P=0.06). The values of total and LDL cholesterol and triglycerides were
      increased post-treatment (P<0.03). In conclusion, while increasing the fasting
      plasma concentration of VLDL and LDL, which are traditional risk factors for
      atherosclerosis, isotretinoin treatment also slows down the metabolism of
      triglyceride-rich lipoproteins such as chylomicrons, as tested by the emulsion
      model, an effect that is also increasingly recognized as atherogenic.

PMID- 16429301
TI  - Proceedings of the 4th eULIS (European Urolithiasis Society) Symposium, Coburg,
      Germany, 16-18 June 2005.

PMID- 16429300
TI  - Protein oxidation and lipid peroxidation after renal ischemia-reperfusion injury:
      protective effects of erdosteine and N-acetylcysteine.
AB  - Oxygen radicals have roles in the renal ischemia-reperfusion (IR) injury usually
      encountered in several conditions such as renal transplantation. The aim of this
      study was to investigate the effects of erdosteine and N-acetylcysteine (NAC) on
      the oxidant/antioxidant status and microscopy of renal tissues after IR injury.
      Male Sprague-Dawley rats were randomly assigned to four groups: control untreated
      rats, IR (30 min ischemia and 120 min reperfusion), IR + NAC (i.p.; 180 mg/kg)
      and IR + erdosteine (oral; 50 mg/kg/day for 2 days before experiments) groups.
      After unilateral renal IR, the right kidney was rapidly excised and sectioned
      vertically into two pieces for microscopic examination and biochemical analysis.
      Erdosteine and NAC treatment did not cause any significant change in the activity
      of superoxide dismutase (SOD) in comparison with the IR group, even if the SOD
      activity increased in IR groups than in the control group. Catalase (CAT)
      activity was decreased in the IR group in comparison with control and IR +
      erdosteine groups (P<0.05), whereas it was higher in the IR + erdosteine group
      than in the IR + NAC group (P<0.05). Xanthine oxidase (XO) activity was higher in
      all the IR-performed groups than in the control group (P<0.05). Thiobarbituric
      acid-reactive substances (TBARS) level and protein carbonyl (PC) content were
      increased after IR injury (P<0.05). Erdosteine or NAC treatments ameliorated
      these increased TBARS and PC contents in comparison with the IR group (P<0.05).
      Light microscopy of the IR group showed tubular dilatation, tubular necrosis and
      vacuole formation in epithelial cells. Erdosteine but not NAC apparently reduced
      the renal tissue damage. The pathological damage score after IR was significantly
      reduced after erdosteine treatment (P<0.05), but not after NAC treatment. In
      conclusion, renal IR resulted in oxidative damage as seen in biochemical lipid
      peroxidation and protein oxidation results with aggravated tubular necrosis.
      Erdosteine and NAC treatments improved the biochemical results of IR injury.
      However, on microscopic evaluations, animals receiving erdosteine showed a great
      reduction in renal damage when compared with the NAC group.

PMID- 16429302
TI  - Male genital tuberculosis in Siberians.
AB  - To study the epidemiology and the clinical picture of male genital tuberculosis
      in Siberia, Russia. Five hundred and fourteen patients with genitourinary
      tuberculosis were enrolled in the study: 414 had kidney tuberculosis only, 100
      had genital involvement. The clinical picture and structure of genital
      tuberculosis were investigated: 42 had tuberculosis of scrotal organs and 58 had
      tuberculosis of the prostate. Urinary cultures, urinalysis, three-glass test, and
      investigation of the prostate secretion, Mycobacteria culture, and susceptibility
      testing were performed in all 514 patients. 33.6% of all patients earlier
      suffered from pulmonary or extrapulmonary tuberculosis and were successfully
      cured. In 61.9% nephrotuberculosis was diagnosed alongside with an
      orchiepididymitis. In 30.9% of patients bilateral epididymorchitis was diagnosed.
      Mycobacteriuria was present in 38.1%. Scrotal fistula was found in 11.9%. In
      66.7% the symptoms appeared acutely. Half of the patients with prostate
      tuberculosis complained of dysuria, 23 (39.6%) had perineal pain, 34 (58.6%) had
      flank pain. Leucocytes in urine were present in 49 (84.5%) patients, and in
      prostatic secretion in 45 (77.6%) patients. Erythrocytes in urine were present in
      31 (53.4%) patients, and in prostatic secretions in 17 (29.3%) patients. Male
      genital tuberculosis has no specific pathognomonic signs. Using a special
      algorithm for the management of patients with prostatitis or epididymitis is
      recommended.

PMID- 16429303
TI  - Development of kidney scars after acute uncomplicated pyelonephritis:
      relationship with clinical, laboratory and imaging data at diagnosis.
AB  - BACKGROUND: Acute pyelonephritis is a potential cause of kidney scars. AIM: To
      evaluate the relationship between clinical, laboratory and imaging data and the
      development of kidney scars in acute pyelonephritis. METHODS: All consecutive
      patients hospitalized for acute uncomplicated pyelonephritis in our nephrology
      unit from June 1996 to June 2004 were considered: 58 females, median age 25.6
      years (16-52). Diagnosis of pyelonephritis required parenchymal lesions shown by
      CT or NMR scan. RESULTS: The lesions were bilateral in 17.2% (10/58) patients,
      unilateral, but multifocal in 81.0% (47/58); at CT or NMR, 65.5% of the lesions
      were classified as simple, 19% with tendency to colliquation and 15.5%
      abscessual. The median interval between first symptoms and diagnosis was 5 days
      (1-25); at referral, only 20.7% had a positive urine culture and 94.8% (55/58)
      had undergone previous antibiotic treatment. The therapeutic protocol required
      intravenous therapy for > or = 2 weeks, followed by 2-4 weeks of oral therapy. At
      6-8 months, the prevalence of kidney scars was 29.3%. Their development was
      highly correlated with the type of lesions at diagnosis (highest risk with
      abscessual lesions; uni- and multivariate analysis). No other clinical or
      laboratory marker (age, fever, positive cultures, levels of acute phase
      reactants, interval between onset and diagnosis) was correlated with the outcome
      (scars). CONCLUSIONS: The type of lesion at diagnosis of acute uncomplicated
      pyelonephritis is highly correlated with the development of kidney scars. Further
      studies are needed to test the therapeutic schedules tailored according to the
      imaging data.

PMID- 16429304
TI  - Subthreshold transpupillary thermotherapy of the retina and experimental
      choroidal neovascularization in a rat model.
AB  - PURPOSE: To study the effect of subthreshold transpupillary thermotherapy (TTT)
      on the retina and experimental choroidal neovascularization (CNV) in the rat.
      METHODS: Subthreshold TTT was performed on normal Brown Norway rats or those with
      krypton laser-induced CNV and appropriate controls with an 810-nm diode laser
      coupled to a slit lamp. At different intervals after TTT, fundus fluorescence
      angiography (FFA) and histopathological examinations were performed. Terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was used to
      detect apoptosis. Immunohistochemistry was used to detect heat shock protein 70
      (Hsp70) expression. RESULTS: In normal retina, edema and whitening was found on
      day 1 after TTT. Different degrees of hyperfluorescence could be seen on FFA.
      Obvious retina damage, especially in the outer layers, was observed by histology
      in all the lesions that appeared whitened. In the CNV there was congestion and
      less damage in the overlying retina than in normal retina on day 1 after TTT.
      Apoptosis was detected in all retinal layers and CNV lesions by TUNEL. In normal
      eyes, after TTT, Hsp70 expression was increased in the inner layers of the retina
      and some of the cells in the choroid. Hsp70 was also increased in laser-induced
      CNV. Two weeks after TTT, the CNV showed a tendency for fibrosis by Masson
      staining. FFA did not show much change in the CNV lesions 2 weeks after TTT.
      CONCLUSION: Subthreshold TTT has adverse effects on the overlying retina and thus
      is likely to cause significant functional and morphological long-term sequelae.
      Subthreshold TTT can cause apoptosis in laser-induced CNV in rats.

PMID- 16429305
TI  - Olfactory dysfunction and its measurement in the clinic and workplace.
AB  - OBJECTIVES: To provide an overview of practical means for quantitatively
      assessing the sense of smell in both the clinic and workplace. To address basic
      measurement issues, including those of test sensitivity, specificity, and
      reliability. To describe and discuss factors that influence olfactory function,
      including airborne toxins commonly found in industrial settings. METHODS:
      Selective review and discussion. RESULTS: A number of well-validated practical
      threshold and suprathreshold tests are available for assessing smell function.
      The reliability, sensitivity, and specificity of such techniques vary, being
      influenced by such factors as test length and type. Numerous subject factors,
      including age, sex, health, medications, and exposure to environmental toxins,
      particularly heavy metals, influence the ability to smell. CONCLUSIONS: Modern
      advances in technology, in conjunction with better occupational medicine
      practices, now make it possible to reliably monitor and limit occupational
      exposures to hazardous chemicals and their potential adverse influences on the
      sense of smell. Quantitative olfactory testing is critical to establish the
      presence or absence of such adverse influences, as well as to (a) detect
      malingering, (b) establish disability compensation, and (c) monitor function over
      time.

PMID- 16429307
TI  - [The development of evidence-based prevention. Health promotion and education as
      an approach to continuous quality improvement of health care].
AB  - Evidence-based health promotion and education relies on the systematic and
      critical discussion of the best available research on the effectiveness of
      interventions. In the last decade, evidence-based reviews provided decisive proof
      for the effectiveness of health promotion and education. The approach is also
      capable of identifying high-quality interventions and deficiencies. Nevertheless,
      there is an ongoing dispute concerning the transfer of evidence-based medicine to
      health promotion and education. Arguments concern databases, research strategies,
      validity and practical applicability of results. A discussion of these issues
      suggests that the methodology of evidence-based medicine is pertinent and
      informative. Some adaptations for health promotion and education would make
      sense, though: contexts and characteristics of interventions should be documented
      and published in rather more detail in order to reach better causal models. Pre
      post studies which are of particular importance for health promotion and
      education should be elaborated according to the psychological multi-trait multi
      method strategy (multiple measurements, modelling of process levels,
      multidimensional operationalization of complex outcomes). All relevant knowledge
      including qualitative studies should be integrated into cycles of theory
      formulation and evidence testing. Finally, a reappraisal of expert opinion is
      proposed relying on specific criteria for the transparency and plurality of
      consensus procedures ruling out conflicts of interest.

PMID- 16429306
TI  - Melanin bearing myoepithelial cells in a pigmented salivary gland carcinoma: a
      new avatar of myoepithelial cell? A case report.
AB  - Melanocytes can be found in the stroma of salivary glands and their tumors.
      However, the presence of melanin pigment in the tumor cells of salivary gland
      origin is exceedingly rare. A 42-year-old man presented with a nasal tumor that
      was black in color. The histology was that of a minor salivary gland carcinoma
      with foci resembling an adenoid cystic carcinoma. The myoepithelial cells of this
      tumor contained melanin pigment. The possible histogenesis of this lesion and an
      explanation for the occurrence of melanin pigment in a salivary gland tumor are
      discussed.

PMID- 16429308
TI  - [Health services research in general practice. A new approach].
AB  - Competence networks in medicine, involving departments of general practice
      (www.kompetenznetze-medizin.de), as well as a large research support program
      "General Practice" funded by the German Federal Ministry of Education and
      Research (www.gesundheitsforschung-bmbf.de/de/439.php) mirror the increasing
      importance of academic general practice for health services research. The use and
      benefit of computerized medical records is exemplified by the classification of
      therapeutic measures and prevalence estimates of diseases. Computerized medical
      records from 134 practices could be extracted via the BDT
      (BehandlungsDatenTrager) interface. Using SQL (structured query language)
      queries, we identified patients with urinary tract infection (UTI), airway
      obstruction and chronic heart failure and the therapeutic management for these
      illnesses. Age and sex of the patients were nearly completely documented in the
      BDT data. Patients with UTI (6,239 consultations) received most often
      cotrimoxazole (69%) and fluoroquinolone (15%), less often trimethoprim (9%) and
      herbal UTI drugs (4%). About half of the 2,714 patients with asthma received
      inhaled steroids, to a somewhat lesser degree than patients suffering from
      chronic obstructive pulmonary disease (50 vs 53%). In a subsample of practices
      (n=44), we identified 4,120 patients with a diagnosis of chronic heart failure.
      Using refined analysis tools, computerized medical records from general practices
      may be helpful to answer relevant questions of health services research and
      contribute to quality assurance in ambulatory patient care.

PMID- 16429309
TI  - [Vitamins and minerals in food supplements. Up-to-date risk assessment].
AB  - The Federal Institute of Risk Assessment (BfR) has applied principles of
      scientific risk assessment to derive proposals for maximum levels of vitamins and
      minerals including trace elements in food supplements and fortified food
      products. This review describes the special features pertaining to the risk
      assessment of these essential micronutrients and the procedure used for the
      derivation of maximum levels for individual food supplements. The applied
      procedure takes into account tolerable upper intake levels (UL), intakes of
      vitamins and minerals in normal daily diets and dietary reference values for the
      derivation of maximum levels in individual food products. In this context,
      consideration must be given to the possibility of multiple exposure via daily
      intakes of several food supplements or several fortified food products. A careful
      risk-benefit analysis was necessary because, with nutrients having a narrow
      margin of safety, the need to compensate for possibly inadequate intakes or
      increased demands had to be weighed against the risk of excessive intakes. With
      nutrients where no UL could be derived due to inadequate databases, the BfR
      recommends that maximum levels should be set on the basis of nutritional
      physiological aspects. It should be noted that this recommendation is based on
      reasons of preventive health protection.

PMID- 16429310
TI  - Unigene derived microsatellite markers for the cereal genomes.
AB  - Unigene derived microsatellite (UGMS) markers have the advantage of assaying
      variation in the expressed component of the genome with unique identity and
      positions. We characterized the microsatellite motifs present in the unigenes of
      five cereal species namely, rice, wheat, maize, Sorghum and barley and compared
      with those in Arabidopsis. The overall UGMS frequency in the five cereal species
      was 1/7.6 kb. The maximum UGMS frequency was in rice (1/3.6 kb) and the lowest in
      wheat (1/10.6 kb). GC-rich trinucleotide repeat motifs coding for alanine
      followed by arginine and the dinucleotide repeat motif GA were found to be
      abundant UGMS classes across all the five cereal species. Primers could be
      designed for 95% (wheat and barley) to 97% (rice) of the identified
      microsatellites. The proportion and frequency of occurrence of long hypervariable
      class I (> or = 20 nucleotides) and potentially variable class II (12-20
      nucleotides) UGMS across five cereal species were characterized. The class I UGMS
      markers were physically mapped in silico on to the finished rice genome and bin
      mapped in wheat. Comparative mapping based on class I UGMS markers in rice and
      wheat revealed syntenic relationships between the two genomes. High degree of
      conservation and cross-transferability of the class I UGMS markers were evident
      among the five cereal species, which was validated experimentally. The class I
      UGMS-conserved orthologous set (COS) markers identified in this study would be
      useful for understanding the evolution of genes and genomes in cereals.

PMID- 16429311
TI  - Rapid recovery of an insect-plant interaction following habitat loss and
      experimental wetland restoration.
AB  - This study examined the impact of wetland habitat loss and isolation on an insect
      plant interaction, and the subsequent rate of recovery of the interaction
      following experimental habitat restoration. We compared herbivore colonisation
      rates and herbivory damage by 'Batrachedra' sp. (Lepidoptera: Coleophoridae) on
      experimentally placed potted Sporadanthus ferrugineus (Restionaceae) plants at
      increasing distances (up to 800 m) from an intact habitat (the source
      population). These tests showed that even a moderate degree of isolation (i.e.
      greater than 400 m) from the intact wetland habitat caused an almost complete
      collapse of the insect-plant interaction, at least in the short term. The number
      of eggs and larvae of colonising 'Batrachedra' sp., as well as average larval
      size and the proportion of S. ferrugineus stems damaged, all decreased
      logarithmically with increasing distance from the intact habitat, presumably due
      to dispersal limitation of the herbivore. Subsequently, to test whether the
      interaction can recover following habitat restoration, we surveyed herbivore
      colonisation rates and herbivory damage on naturally regenerated S. ferrugineus
      plants on experimentally restored 'islands' at increasing distances (up to 800 m)
      from an intact habitat. The rate of recovery of the interaction was surprisingly
      rapid (i.e. between 196 and 308 weeks). The degree of difference in the density
      of eggs and larvae, and in the proportion of stems damaged with increasing
      isolation from the intact wetland, gradually diminished over 196 weeks. After 308
      weeks there was no significant difference in the insect-plant interaction between
      the intact wetland sites and any of the experimentally restored sites up to 800 m
      away. These results suggest that some insect-plant interactions can recover
      rapidly from habitat loss with restoration management.

PMID- 16429312
TI  - Small-scale experimental habitat fragmentation reduces colonization rates in
      species-rich grasslands.
AB  - Habitat fragmentation is one of the most important threats to biodiversity.
      Decreasing patch size may lead to a reduction in the size of populations and to
      an increased extinction risk of remnant populations. Furthermore, colonization
      rates may be reduced in isolated patches. To investigate the effects of isolation
      and patch size on extinction and colonization rates of plant species, calcareous
      grasslands at three sites in the Swiss Jura Mountains were experimentally
      fragmented into patches of 0.25, 2.25, and 20.25 m2 by frequent mowing of the
      surrounding area from 1993 to 1999. Species richness in the fragment plots and
      adjacent control plots of the same sizes was recorded during these 7 years. In
      agreement with the theory of island biogeography, colonization rate was reduced
      by 30% in fragments versus non-isolated controls, and extinction increased in
      small versus large plots. Habitat specialists, in contrast to generalists, were
      less likely to invade fragments. In the last 4 years of the experiment,
      extinction rates tended to be higher in fragment than in control plots at two of
      the three sites. Despite reduced colonization rates and a tendency of increased
      extinction rates in fragments, fragmented plots had only marginally fewer species
      than control plots after 7 years. Hence, rates were a more sensitive measure for
      community change than changes in species richness per se. From a conservation
      point of view, the detected reduced colonization rates are particularly
      problematic in small fragments, which are more likely to suffer from high
      extinction rates in the long run.

PMID- 16429313
TI  - Variation in larval growth can predict the recruitment of a temperate, seagrass
      associated fish.
AB  - Understanding the factors leading to inter-annual variation in recruitment of
      animals with complex life cycles is a key goal for ecology and the sustainable
      management of animal resources, such as fisheries. We used otolith microstructure
      to determine larval growth rates of post-larval King George whiting, Sillaginodes
      punctata, in seagrass beds of Port Phillip Bay, Australia. Inter-annual variation
      in growth determined early in the pelagic, offshore larval-stage was highly
      correlated with post-larval abundance (a predictor of fishery recruitment). Sea
      surface temperature measured near the presumed spawning area off Western Victoria
      was significantly correlated with larval growth, and was also significantly
      correlated with post-larval abundance in Port Phillip Bay. Increased water
      temperature would have had the direct effect of increasing larval growth and
      therefore contributing to larval survival, but may also have been indicative of
      enhanced physical transport and/or plankton productivity. Overall, larval growth
      rate of King George whiting is a very strong predictor of post-larval abundance,
      which in turn will influence fishery recruitment in 3-5 years' time.

PMID- 16429314
TI  - Ri antibodies in patients with breast, ovarian or small cell lung cancer
      determined by a sensitive immunoprecipitation technique.
AB  - The presence of circulating antineuronal antibodies has been associated with
      paraneoplastic neurological syndromes (PNS). Ri antibodies are often associated
      with lung or breast cancer, but the prevalence of such antibodies in large cancer
      materials is largely unknown. We used a highly sensitive immunoprecipitation
      assay to study the level of Ri antibodies in blood samples from 200 patients with
      small cell lung cancer (SCLC), 253 patients with breast cancer and 557 patients
      with ovarian cancer. Two hundred blood donors and six Ri positive PNS patients
      served as controls. The recombinant antigen used in the immunoprecipitation assay
      was radiolabeled by a coupled in vitro transcription and translation (ITT)
      technique, enabling low levels of antibodies to be detected. None of the blood
      donors contained Ri antibodies, whereas all of the sera from the PNS patients
      were positive. Ri antibodies were present in 4.5% of the patients with SCLC, 0.8%
      of the patients with breast cancer and in 0.2% of the patients with ovarian
      cancer. Retesting of the Ri positive samples with immunofluorescense and immune
      blot showed that the immunoprecipitation technique was more sensitive than the
      other immune assays. Ri antibodies were not associated with PNS in the patients
      with breast or ovarian cancer. Neurological data were not available for the SCLC
      patients, but in these, Ri antibodies were not associated with survival.

PMID- 16429316
TI  - Fixing the conformations of diamineplatinum(II)-GpG chelates: NMR and CD
      signatures of individual rotamers.
AB  - The bulky, asymmetric analog of the antitumor drug cisplatin, [PtCl(2)(tmen)]
      (tmen = N,N,N'-trimethylethylenediamine), was used to produce crosslinks with the
      dinucleotide d(GpG), modeling the most frequent lesions that cisplatin and its
      analogs cause to DNA. The ligand tmen was chosen because it is expected to
      constrain the guanine cis to the NMe(2) group in the adduct [Pt(tmen){d(GpG)}](+)
      to an orientation perpendicular to the coordination plane and to stabilize the
      other guanine in an oblique orientation, thus maintaining a head-to-head geometry
      typical of cisplatin-d(GpG) crosslinks within single- and double-stranded DNA. Of
      the four possible combinations of tmen chirality (R or S symmetry of the
      coordinated NHMe group) and crosslink direction (5'-G bound cis to the secondary
      or the tertiary amino group of tmen), two isomers were preponderantly formed,
      [Pt(R-tmen){d(GpG)}](+) with 5'-G bound cis to NMe(2) and [Pt(S-tmen){d(GpG)}](+)
      with 5'-G bound cis to NHMe. The former was shown to have a right-handed R2
      orientation of guanines similar to that found in duplex DNA, whereas the latter
      had a left-handed L1 orientation that modeled cisplatin-d(GpG) adducts within
      single-stranded DNA. The R2 rotamer was found to be in an equilibrium (as
      observed using EXSY spectroscopy) with a minor fraction (< or =4%) of a Delta-HT
      rotamer related to R2 by rotation of the 3'-G about the Pt-N7 bond. The major
      rotamers R2 and L1 were isolated using reverse-phase HPLC, and their NMR and CD
      signatures were compared to those of the corresponding rotamers of the less
      hindered adduct [Pt(dmen)(GpG)](+) (dmen = N,N-dimethylethylenediamine). From
      this and other comparisons with previously reported platinum dinucleotide
      complexes, and from molecular modeling, it could be concluded that both steric
      repulsion between guanine and substituents of the cis amino group and N-H...O6
      hydrogen bonding are significant effects favoring the oblique orientation of one
      guanine base typical of the HH rotamers of [Pt(diamine){d(GpG)}](+) and
      [Pt(diamine)(GpG)](+) complexes.

PMID- 16429315
TI  - The current status of natural products from marine fungi and their potential as
      anti-infective agents.
AB  - A growing number of marine fungi are the sources of novel and potentially life
      saving bioactive secondary metabolites. Here, we have discussed some of these
      novel antibacterial, antiviral, antiprotozoal compounds isolated from marine
      derived fungi and their possible roles in disease eradication. We have also
      discussed the future commercial exploitation of these compounds for possible drug
      development using metabolic engineering and post-genomics approaches.

PMID- 16429318
TI  - Horizontal fracture of the anterior arch of the atlas associated with a
      congenital cleft of the anterior arch.
AB  - We report a rare combination of a horizontal fracture of the anterior arch of the
      atlas associated with a congenital cleft of the anterior arch. Sagittally
      reformatted computed tomography (CT) images demonstrated a fracture of the
      anterior arch of the atlas and a type II odontoid process fracture. There was
      also a smoothly marginated midline cleft of the anterior arch just above the
      fracture consistent with a congenital variant. 3D CT images were helpful in the
      evaluation of the fractures and the developmental variant. Magnetic resonance
      imaging showed a spinal cord injury. The patient underwent posterior C1-C2
      fusion.

PMID- 16429317
TI  - The effect of sensitisation to insulin with pioglitazone on fasting and
      postprandial lipid metabolism, lipoprotein modification by lipases, and lipid
      transfer activities in type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: Insulin resistance is thought to be central to the pathogenesis
      of diabetic dyslipidaemia. We hypothesised that improving insulin sensitivity
      would improve fasting and postprandial triglyceride metabolism in patients with
      type 2 diabetes. To this aim we studied fasting and postprandial lipaemia in type
      2 diabetic patients before and after sensitisation to insulin with pioglitazone,
      compared with that observed in patients on an insulin-providing regime. METHODS:
      In a double-blind placebo-controlled protocol, 22 patients with type 2 diabetes
      were randomly allocated to receive either pioglitazone (45 mg/day) or
      glibenclamide (5 mg/day), for a 20-week period. Fasting and postprandial lipid
      metabolism were investigated at baseline and at the end of the treatment period.
      A group of non-diabetic subjects was also studied. RESULTS: Compared with
      glibenclamide treatment, pioglitazone treatment decreased fasting triglyceride,
      glucose and insulin levels and the homeostasis model assessment score of insulin
      resistance. Decreased fasting triglyceride after pioglitazone treatment was due
      to reduced VLDL triglyceride, particularly VLDL-2. Lipoprotein lipase activity
      was unchanged by pioglitazone treatment but hepatic lipase showed a significant
      decrease. Pioglitazone treatment lowered total postprandial triglyceride, as well
      as chylomicron- and chylomicron-remnant retinyl palmitate levels to normal.
      Glucose disposal improved but remained abnormal. CONCLUSIONS/INTERPRETATION:
      Insulin sensitisation with pioglitazone has major effects in restoring
      postprandial lipaemia to normal, while also correcting fasting
      hypertriglyceridaemia; both factors may have consequences for atherogenic risk in
      diabetes.

PMID- 16429321
TI  - Post-coital bleeding: a rare and unusual presentation of cervical endometriosis.
AB  - INTRODUCTION: Often due to benign conditions such as cervical ectopy, post-coital
      bleeding is a distressing symptom for the patient. However, for the clinician,
      the identification of the etiology is important in order to effect proper
      treatment. CASE REPORT: We present a case referred to the colposcopy clinic
      because of post-coital bleeding and a smear report of 'groups of benign glandular
      cells of endometrial origin'. Colposcopy was normal but histology of an excised
      haemorrhagic nodule revealed endometriosis with resolution of symptoms.
      CONCLUSION: Cervical endometriosis should be considered in the differential
      diagnosis of post-coital bleeding with no obvious ectopy or malignancy.

PMID- 16429320
TI  - Can dissenting findings regarding the comparative effectiveness of ICSI and IVF
      be explained by a learning curve?
AB  - PURPOSE: To determine whether between-trial heterogeneity in relative risk of
      fertilisation for intracytoplasmic sperm injection (ICSI) compared to in vitro
      fertilisation (IVF) can be explained by learning or by between-trial variation in
      patient characteristics. METHODS: Systematic review and meta-analysis of trials
      comparing fertilisation outcomes for ICSI and IVF (without surgical sperm
      retrieval). Meta-regressions to identify associations between treatment effect
      and trial characteristics. RESULTS: Coefficients on individually significant
      covariates from the meta-regressions confirm that the ICSI versus IVF treatment
      effect is increased when patients are "unsuited for IVF" but reduced as semen
      quality improves and when IVF insemination concentrations are increased. However,
      the relative risk of fertilisation varies inversely with publication date;
      contrary to the hypothesised learning effect. CONCLUSION: While it is recognised
      that publication date might proxy for unobserved covariates, the possibility of a
      learning effect in favour of ICSI is not supported by the meta-regression.

PMID- 16429322
TI  - Disruption of clc-5 leads to a redistribution of annexin A2 and promotes calcium
      crystal agglomeration in collecting duct epithelial cells.
AB  - Mutations in CLCN5, which encodes the voltage-dependent Cl(-)/H(+)antiporter, CLC
      5, cause Dent's disease. This disorder is characterized by low molecular-weight
      proteinuria, hypercalciuria, nephrocalcinosis and nephrolithiasis. Using a
      collecting duct cell model (mIMCD-3) in which endogenous clc-5 is disrupted by
      antisense clc-5 or overexpression of truncated clc-5, we demonstrate altered
      expression of the crystal adhesion molecule, annexin A2. Endogenously expressed
      annexin A2 is intracellular with limited plasma membrane localization. Following
      clc-5 disruption, there is both a marked increase in plasma membrane annexin A2
      and an increase in cell surface crystal retention and agglomeration, which may be
      attenuated using pretreatment with anti-annexin A2 antibodies or wheat germ
      agglutinin lectin but not by concanavalin A. We hypothesize that in Dent's
      disease, endocytic failure leads to an accumulation at the plasma membrane of
      crystal-binding molecules that include annexin A2 leading to retention of calcium
      crystals and ultimately nephrocalcinosis and nephrolithiasis.

PMID- 16429323
TI  - Analysis of a sub-proteome which co-purifies with and is phosphorylated by the
      Golgi casein kinase.
AB  - In an attempt to gain information about the identity of the Golgi apparatus
      casein kinase(s) (G-CK), responsible for the phosphorylation of caseins in
      lactating mammary gland, the proteins present in fractions enriched in G-CK
      activity eluted from DEAE-Sepharose and heparin-Sepharose columns were resolved
      by two-dimensional electrophoresis and analyzed by mass spectrometry. This led to
      the identification of 47 proteins altogether, none of which is a bona fide
      protein kinase. At least 9 of the identified proteins however, are readily
      phosphorylated by co-purifying G-CK activity, and 7 are physically associated
      with it to give supramolecular complex(es) of about 500 kDa as judged from
      Superdex S200 gel fitration and glycerol gradient ultracentrifugation
      experiments. In contrast, the apparent molecular weight of G-CK estimated from an
      in gel activity assay after SDSPAGE and renaturation is about 41 kDa. Many of the
      proteins phosphorylated by and/or associated with G-CK belong to the category of
      chaperonines, including HSP90, GRP-94 and -78, and various isoforms of protein
      disulfide isomerases, suggesting a global role of this kinase in the modulation
      of protein folding.

PMID- 16429324
TI  - Etiologic factors in Paget's disease of bone.
AB  - Paget's disease of bone is a chronic focal skeletal disorder characterized by
      increased bone resorption by the osteoclasts. Paramyxoviral gene products have
      been detected in pagetic osteoclasts. Paget's disease is an autosomal dominant
      trait with genetic heterogeneity. Several mutations in the ubiquitin-associated
      (UBA) domain of sequestosome 1 (SQSTM1/p62) have been identified in patients with
      Paget's disease. Similarly, mutations in the valosin-containing protein (VCP)
      gene have been shown to cause inclusion body myopathy associated with Paget's
      disease of bone and frontotemporal dementia. In addition, gene polymorphisms and
      enhanced levels of cytokine/growth factors associated with Paget's disease have
      been identified. However, the etiologic factors in Paget's disease remain
      elusive. A cause and effect relationship for the paramyxoviral infection and
      SQSTM1/ p62 gene mutations responsible for pagetic osteoclast development and
      disease severity are unclear. This article will highlight the etiologic factors
      involved in the pathogenesis of Paget's disease.

PMID- 16429325
TI  - Galectin-7.
AB  - Galectins are a family of animal lectins with an affinity for beta-galactosides.
      They are differentially expressed by various tissues and appear to be
      functionally multivalent, exerting a wide range of biological activities both
      during development and in adult tissue. Galectin-7, a member of this family,
      contributes to different events associated with the differentiation and
      development of pluristratified epithelia. It is also associated with epithelial
      cell migration, which plays a crucial role in the re-epithelialization process of
      corneal or epidermal wounds. In addition, recent evidence indicates that galectin
      7, designated as the product of the p53-induced gene 1 (PIG1), is a regulator of
      apoptosis through JNK activation and mitochondrial cytochrome c release. Defects
      in apoptosis constitute one of the major hallmarks of human cancers, and galectin
      7 can act as either a positive or a negative regulatory factor in tumour
      development, depending on the histological type of the tumour.

PMID- 16429326
TI  - Inositol pyrophosphates: metabolism and signaling.
AB  - Inositol pyrophosphates belong to the diverse family of inositol polyphosphate
      species that have a range of signaling functions. Since the discovery of inositol
      pyrophosphates in the early 1990s, enormous progress has been achieved in
      characterising this class of molecules, linking their biological presence to a
      wide range of cellular functions, including vesicular trafficking, apoptosis,
      telomere maintenance and protein phosphorylation. The activity of inositol
      pyrophosphates appears to be related to their rapid turnover in cells and also to
      their pyrophosphate groups, which are considered to contain high-energy bonds.
      Together, these observations suggest that inositol pyrophosphates may represent a
      class of cellular messengers with basic and not yet fully characterised
      functions. This review aims at summarising the recent progress of our knowledge
      of this exciting class of molecules, from inositol pyrophosphate discovery to the
      description of their physiological functions.

PMID- 16429327
TI  - Psychosis complicating Chorea gravidarum.

PMID- 16429330
TI  - [Clinical neuropsychology and the German statutory health system].

PMID- 16429331
TI  - [Evidence based treatment of executive dysfunction].
AB  - The therapy of executive functions plays an essential role for the functional
      outcome and the social reintegration. Nevertheless there is a lack of cognitive
      oriented and evidence-based therapy programs. The purpose of our review is the
      classification of the present evaluation studies with regard of the principles of
      evidence based medicine (EbM) and of the content. Besides the EbM criteria the
      number of participants, the kind and number of interventions, the types of
      etiology and the standardisation and quality of the outcome parameters are
      measured. By that, an assessment should be possible, which interventions are
      successful for what types of dysexecutive syndrome. The present studies belong to
      three different types of therapy: at first, a therapy form focussing on
      manipulation and modification of the environment, second, a therapy form using
      behaviour management and a third form, which is based on practise and cognitive
      interventions. The heterogeneity of the therapy forms makes different types of
      evaluation necessary. The evaluation studies reach different classes of evidence.
      While the cognitive therapy forms reach comparable high evidence classes, the
      evaluation studies about behaviour management--mostly present as single case
      studies with individual outcome parameter--reach only low evidence classes.
      Final, we discuss, which therapy forms are effective using the strong evaluation
      criteria and at which point further conceptual task and further research is
      useful.

PMID- 16429332
TI  - [The effectiveness of psychosocial treatment approaches for alcohol dependence--a
      review].
AB  - Treatment approaches which are used in the context of inpatient alcoholism
      treatment are frequently neither theoretically justified nor empirically
      examined. In view of the enormous method variety the necessity exists for the
      development of treatment guidelines in order to offer indicators of promising
      treatment achievement for practitioners and pension funds. In a first step, it
      must be examined which treatments are effective, which are ineffective and which
      are possibly even counter-productive. This article aims to give a comprehensive
      review of randomized-controlled studies/meta-analysis on the efficacy of
      different treatment approaches. This article reporting the literature review is
      part of a larger programme to develop clinical practice guidelines for
      rehabilitation which is supported in form, content and finance by the German
      Pension Institute for Salaried Employees (Bundesversicherungsanstalt fur
      Angestellte, BfA). Summing up, treatment is effective compared to no treatment.
      Cognitive behavioural therapy included in a multimodal treatment program is
      effective. There are a number of treatment protocols for which controlled
      research has consistently found positive results like social skills training,
      community reinforcement approaches, behaviour contracting, motivation-enhancing
      treatment, and family/marital therapy. There is also a number of commonly used
      treatment approaches that brought neither a positive result or were counter
      productive like relapse prevention, non-behavioural marital therapy, and insight
      psychotherapy, confrontational counseling, education, relaxation training, and
      milieu therapy. Support for matching to a specific treatment is weak, but
      interventions against alcohol problems should be differentiated according to the
      severity of the alcohol problem. Since treatment evaluation is mainly
      accomplished in the US and supplying structures with respect to the US and
      Germany are substantially different, a generalized transmission of US-American
      research results on Germany is to be evaluated carefully. Randomized-controlled
      studies are needed in Germany.

PMID- 16429333
TI  - [Obsessive-compulsive disorder and schizophrenia. A critical review].
AB  - Co-occurrence of psychotic and obsessive-compulsive symptoms has been recognized
      for decades. This paper reviews published reports from five perspectives:
      schizophrenia with obsessive-compulsive symptoms, obsessive-compulsive disorder
      (OCD) with psychotic symptoms, schizophrenia-spectrum-personality disorder with
      obsessive-compulsive symptoms, obsessive-compulsive symptoms induced by atypical
      antipsychotics and similarities of functional neural circuits theory in OCD and
      schizophrenia. A MEDLINE search was conducted to identify relevant articles from
      1960 until 2004. Only a few systematic data that explore the nature and
      significance of such occurrence have been published. More recent studies using
      systematic diagnostic criteria suggest that the rate of occurrence may not be
      rare at all. In schizophrenia, a similar dorsolateral prefrontal cortex circuit
      shares anatomic substrates similar to those of the OCD orbitofrontal circuit.
      Exploring the interface of schizophrenic and obsessive-compulsive symptoms is
      important for diagnostic clarity and could have important implications for
      treatment and long-term prognosis. The review emphasizes the different origins
      and natural course of co-occurrence of schizophrenic and obsessive-compulsive
      symptoms and their various outcome under atypical antipsychotics and selective
      serotonin reuptake inhibitors (SSRI). Further double-blind, randomized, placebo
      controlled investigations in larger cohorts of schizophrenic and OCD patients are
      needed in order to identify a schizo-obsessive schizophrenia and a schizotypal
      subtype of obsessive compulsive disorder and to substantiate the algorithm for
      treatment.

PMID- 16429334
TI  - [Diagnostics and treatment of delirium tremens--not caused by alcohol or other
      psychotropic substances].

PMID- 16429336
TI  - [Short and long-term results of balloon mitral valvotomy].
AB  - BACKGROUND: Since its introduction in the eighties by Inoue, percutaneous balloon
      valvotomy has been established as treatment of choice for symptomatic
      degenerative mitral stenosis. Especially young patients with rheumatic fusion of
      the mitral commissures and no calcification of the still pliable valve leaflets
      are candidates for this procedure. In these patients balloon valvotomy is
      expected to give results comparable or even superior to operative commissurotomy.
      PATIENTS AND METHODS: This report presents the short and long-term results of 33
      patients (24 females, 9 males; median age: 53 years) that underwent percutaneous
      mitral valvotomy (PMV) at the cardiac unit of the university hospital in Cologne
      during the last three years. RESULTS: The intervention was immediately successful
      in 31 patients (94%). The median mitral valve area was increased after PMV to 2.0
      +/- 0.5 cm(2) an increase of mean opening area of 82% and a decrease of mean
      pressure gradient by about 50%. Follow-up date at 12 and 24 months were available
      for 21 and 12 patients, respectively. During the first 12 months after
      intervention four patients subsequently had to have surgical mitral valve
      replacement, one of them together with a coronary artery bypass graft. One
      patient, who had undergone PMV in cardiogenic shock died after the intervention.
      A 12-month follow-up demonstrated a mean mitral valve area of 1.7 +/- 0.4 cm(2)
      as assessed by echocardiography. After 24 months comparable mean valve area was
      1.7 +/- 0.4 cm(2). One other patient required operative valve replacement, but
      there were no further deaths. CONCLUSION: The data collected from this very
      heterogeneous group of patients at the cardiac unit of the university hospital in
      Cologne confirms the observation that PMV is beneficial in young patients with
      favorable valve morphology and shows that it is indicated not only as a
      palliative measure but also as treatment option in older patients with more
      complex alterations of the mitral valve.

PMID- 16429335
TI  - [The modified Bonn Malmo protocol (MBMP) in the treatment of acquired haemophilia
      A].
AB  - BACKGROUND AND OBJECTIVE: Autoantibodies directed against clotting factors can
      induce life threatening bleeding with a mortality rate up to 22%. Although the
      incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long
      term clotting factor substitution can be enormous. Aim of an optimal treatment
      strategy should be to control bleedings by a rapid and safe elimination of the
      inhibitor and reinducing long-term immune tolerance. PATIENTS AND METHODS:
      Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD
      16.4)), the largest patient collective world-wide, was monitored for a mean of 48
      months. Three patients received only conservative treatment. 45 patients were
      treated intensively by a multimodal strategy including: 1. immunoadsorption for
      antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin
      substitution and 4. immunosuppression. The times required for inhibitor
      elimination, factor VIII substitution and the duration of the MBMP were
      documented. RESULTS: In 45 patients with a high titre critical bleeding was
      controlled immediately after the initiation of MBMP. There were no deaths from
      bleeding or the treatment. Inhibitor levels decreased to undetectable levels
      within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated
      within a median of 13 days (95% CI, 10-16 days) and the treatment was completed
      within a median of 15 days (95% CI, 13-17 days). The overall response rate for
      complete remission (CR) was 91%. When cancer patients were excluded, the CR rate
      was 97%. CONCLUSION: Considering the short duration and amount of factor VIII
      substitution, the short time of hospitalization and the long-term median follow
      up of 48 months without bleeding events, the MBMP appears to have a modifying
      effect on the immunological response.

PMID- 16429337
TI  - [Mental disorders associated with multiple sclerosis].
AB  - HISTORY: Findings are reported in 4 patients with multiple sclerosis (MS) and
      various mental disorders which were directly associated with the underlying
      disease, with disease-related increased vulnerability, were a reactive response
      or had occurred independently of the MS. CASE 1: A 53-year-old woman with MS for
      24 years developed cognitive disorders with markedly impaired quality of life.
      CASE 2: A 44-year-old man with MS for 8 years had depression and felt suicidal.
      CASE 3: A 58-year-old woman with MS for 35 years suffered from both depression
      and symptoms of a compulsive-obsessive disorder. CASE 4: A 19-year-old woman with
      MS for 2 years was treated by a psychiatrist for the first time when she
      developed acoustic hallucinations and suicidal ideation during cortisone
      treatment. DIAGNOSIS, TREATMENT AND COURSE: CASE 1: The progressive mental
      disorder was classified as manifestation of the chronic progressive MS: it was
      treatment-refractory. CASE 2: The patient underwent psychotherapy as both an in-
      and out-patient. His depression was thought to be reactive and improved well
      under this treatment, despite the deterioration of the MS, requiring him to use a
      wheel-chair. CASE 3: The compulsive-obsessive symptoms persisted during
      medication for depression, for which she then received behavioral treatment. CASE
      4: The initial symptoms of hallucination and suicidal ideation ceased when
      cortisone was stopped. A diagnosis of borderline personality was made, based on
      her continuing symptoms of impaired impulse control, abnormal affect, distorted
      self-image, a feeling of inner emptiness, agitation with suicidal tendency and
      factitious injuries. The renewed occurrence of acoustic hallucinations and
      suicidal tendency occurred independently of cortisone treatment and was
      interpreted as expression of inflammatory disease activity, but differential
      diagnosis had to consider the patient s personality disorder, too. CONCLUSION:
      Mental disorders in patients with MS are manifold and their causes are complex.
      It is important to recognize these associated diseases and initiate
      individualized treatment, because they considerably impair the patients quality
      of life.

PMID- 16429339
TI  - [Diagnostic procedures and therapeutic options in xanthogranulomatous
      pyelonephritis -- experience gathered in Erlangen].

PMID- 16429340
TI  - [Brain metastases of lung cancer].
AB  - Cerebral metastases are a frequent complication of lung cancer. They often
      determine patients' prognosis and need urgent therapeutic intervention. Based on
      histologic type, former therapies, age and performance of the patient, the number
      of cerebral lesions and the extracerebral tumour activity, individualized
      treatments are applied. For patients who suffer from non-small cell lung cancer
      and a single CNS lesion the best results can be achieved if they are surgically
      resected or receive radiosurgery. Their survival time can be markedly increased
      in comparison to patients who undergo whole brain irradiation. If multiple
      metastases are seen in CT or MRI, whole brain irradiation is the therapy to
      choose. Furthermore it should be initiated if small cell lung cancer metastasizes
      to the brain. More aggressive local treatment options appear promising, but a
      clear role for them has not yet been defined. Systemic chemotherapy gains more
      attention in the treatment of small and non-small cell lung cancer with brain
      metastases. How to increase the efficacy through simultaneous application of
      chemo- and radiotherapy is tested in current trials. This article gives an
      overview on clinical presentation and diagnosis of cerebral metastases in lung
      cancer and reviews current treatment options.

PMID- 16429341
TI  - [Obligations to medical care in the area of certification--decision of the Munich
      Provincial Court on July 27 2004]l].

PMID- 16429343
TI  - [Adherence to guidelines in the treatment of heart failure in Germany(results of
      the MAHLER Study)--from DMW 39/2005].

PMID- 16429344
TI  - [Should one always think of osteoporosis when ruling out multiple myeloma?-
      responding to DMW 28/29/2005].

PMID- 16429346
TI  - Ulcers and gastritis.

PMID- 16429347
TI  - Colonoscopy, tumors, and inflammatory bowel disease - new diagnostic methods.
AB  - Accurate detection of premalignant lesions and early cancers in the colon is
      essential for curative endoscopic or surgical therapy, since the prognosis for
      the affected patients is closely related to the size and stage of the neoplastic
      lesion. Total colonoscopy is the accepted gold standard for screening and
      surveillance of colorectal cancer. This review summarizes recently published
      diagnostic developments and key findings in the areas of colonoscopy, colonic
      tumors, and inflammatory bowel diseases. Relevant findings have been reported for
      chromo-endoscopy in the diagnosis of colitis-associated neoplasia, as well as
      flat and depressed adenomas. Real-time Doppler capabilities have now been added
      to endoscopic optical coherence tomography; the results of large-scale testing of
      narrow-band imaging endoscopy in the colon are being awaited; and fluorescence
      imaging has recently been added to the facilities available in video endoscopy.
      Most importantly, endomicroscopy now for the first time allows single-cell
      subsurface imaging during ongoing colonoscopy procedures, opening the way to in
      vivo molecular and functional imaging.

PMID- 16429348
TI  - ERCP and biliary topics.

PMID- 16429349
TI  - Endoscopic ultrasonography.

PMID- 16429350
TI  - Small-bowel endoscopy.

PMID- 16429351
TI  - PillCam ESO in esophageal studies: improved diagnostic yield of 14 frames per
      second (fps) compared with 4 fps.
AB  - BACKGROUND AND STUDY AIM: Capsule endoscopy, using the PillCam ESO and sending
      images at a rate of 4 frames per second (fps), has a high sensitivity and
      specificity in diagnosing gastroesophageal reflux disease (GERD) lesions. We
      tested a new device which produces images at a rate of 14 fps. The diagnostic
      performance and esophageal visualization of these two devices were compared.
      PATIENTS AND METHODS: 42 patients with GERD symptoms and eight patients with a
      history of Barrett's esophagus had an esophagogastroduodenoscopy (EGD). All
      patients underwent capsule endoscopy of the esophagus within 1 hour prior to EGD.
      The first 25 patients had a capsule endoscopy examination with the 4-fps device.
      The following 25 patients underwent capsule endoscopy under identical conditions
      but using the 14-fps device. The reader of the capsule endoscopy study was
      blinded to the EGD findings. A diagnosis of GERD or Barrett's esophagus was
      established with EGD. The findings at capsule endoscopy were compared with the
      EGD findings. We also examined how frequently the esophagus in its entirety was
      visualized by these two devices. RESULTS: The 4-fps device diagnosed 16/19 cases
      of esophageal erosions or ulcers (sensitivity 84 %) and 6/8 cases of Barrett's
      esophagus (sensitivity 75 %). The 14-fps capsule diagnosed 16/16 cases of
      esophageal ulcers or erosions and 7/7 cases of Barrett's esophagus (sensitivity
      100 %). The total diagnostic miss rate in the 4-fps group was 5/27 (18 %) whereas
      the diagnostic miss rate in the 14-fps group was 0/23 (0 %) P < 0.02). The upper
      esophageal sphincter (UES) was clearly identified in 6/25 patients (24 %) in the
      4-fps group and in 20/25 patients (80 %) in the 14-fps group ( P < 0.01). The
      entire esophagus was well visualized in 3/25 patients (12 %) by the 4-fps device
      and in 19/25 (76 %) by the 14-fps device ( P < 0.01). The superiority of the 14
      fps PillCam ESO capsule is consistent with the data obtained from fluoroscopic
      studies of swallowed PillCam capsules, showing that capsule speed may reach 20
      cm/s. For the 14-fps PillCam this means one image transmitted per 3-cm segment at
      maximal capsule speed, therefore still allowing for full visualization of the
      entire esophagus. CONCLUSIONS: Capsule endoscopy using the 14-fps PillCam ESO
      showed a greater sensitivity than that of the 4-fps device for identifying GERD.
      The 14-fps PillCam ESO was statistically superior to the 4-fps device in
      visualizing the opening of the UES and the entirety of the esophagus.

PMID- 16429352
TI  - The accuracy of PillCam ESO capsule endoscopy versus conventional upper endoscopy
      for the diagnosis of esophageal varices: a prospective three-center pilot study.
AB  - BACKGROUND AND STUDY AIMS: Variceal bleeding is a major complication of
      cirrhosis, and is associated with a 20 % mortality at 6 weeks. Current
      international guidelines recommend that patients with cirrhosis are screened by
      conventional upper endoscopy (esophagogastroduodenoscopy, EGD) in order to detect
      esophageal varices. The recently developed PillCam ESO esophageal capsule
      endoscope has been shown to be an accurate diagnostic tool in the investigation
      of patients with gastroesophageal reflux and Barrett's esophagus. We compared the
      PillCam ESO capsule endoscope with EGD for the detection of esophagogastric
      varices and portal hypertensive gastropathy in patients with cirrhosis. PATIENTS
      AND METHODS: A pilot trial was conducted at three sites. Patients with cirrhosis
      who were undergoing clinically indicated EGD for screening or surveillance for
      esophageal varices underwent a PillCam ESO study followed by an EGD within 48
      hours. Capsule videos were assessed by an investigator who was blinded to the
      patient's medical history and EGD findings. RESULTS: A total of 23 of the 32
      enrolled patients were found to have esophageal varices at both EGD and PillCam
      ESO endoscopy. In one patient PillCam ESO detected small varices that were not
      seen at EGD. The overall concordance between PillCam ESO and EGD was 96.9 % for
      the diagnosis of esophageal varices and 90.6 % for the diagnosis of portal
      hypertensive gastropathy. There were no adverse events related to PillCam ESO
      endoscopy. CONCLUSIONS: In a high-prevalence population, PillCam ESO may
      represent an accurate noninvasive alternative to EGD for the detection of
      esophageal varices and portal hypertensive gastropathy. A large-scale trial is
      underway to validate and expand these findings.

PMID- 16429353
TI  - Esophageal capsule endoscopy versus esophagogastroduodenoscopy for evaluating
      portal hypertension: a prospective comparative study of performance and
      tolerance.
AB  - BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) is the most effective
      method for examining the upper gastrointestinal tract, and particularly for
      evaluating portal hypertension in cirrhotic patients, especially for screening
      purposes. The aim of this study was to assess the feasibility, safety, accuracy,
      and tolerance of PillCam ESO capsule endoscopy for this indication. PATIENTS AND
      METHODS: In this prospective study, unsedated EGD and capsule endoscopy
      examinations were conducted on the same day in cirrhotic patients at the time of
      diagnosis. The patients quantified the tolerability (relative to pain, nausea,
      choking sensations, etc.) of the two procedures using a 100-mm visual analogue
      scale. The time required for the recording and for diagnosis with the capsule
      examination were documented, as were the patients' preferences in comparison with
      EGD. Two independent endoscopists blinded to the EGD diagnoses assessed the
      diagnostic accuracy of the images obtained. RESULTS: Twenty-one patients were
      included in the study (mean age 62, mean Model for End-Stage Liver Disease score
      10.5, mean Child-Pugh score 7.3). The procedure was safe. One patient was unable
      to swallow the capsule. The mean recording time was 213 s (range 6 - 1200 s); the
      procedure accurately assessed the presence or absence of esophageal varices in 16
      of 19 patients (84.2 %); and it correctly indicated a need for primary
      prophylaxis (esophageal varices of grade 2 or more and/or red signs) in 100 % of
      cases. The tolerability of the capsule endoscopy examination was significantly
      better, and all of the patients preferred capsule endoscopy to EGD (which was
      transnasal in 11 patients). CONCLUSIONS: Capsule endoscopy was feasible, safe,
      accurate, highly acceptable, and preferred by cirrhotic patients undergoing
      screening for portal hypertension. This new technique requires further and more
      extensive evaluation, as well as assessment of its cost-effectiveness.

PMID- 16429354
TI  - Double-balloon enteroscopy: indications, diagnostic yield, and complications in a
      series of 275 patients with suspected small-bowel disease.
AB  - BACKGROUND AND STUDY AIMS: Until recently, only the proximal small bowel was
      accessible for diagnostic and therapeutic endoscopy. This paper describes
      experience in the first 275 patients examined and treated with the new method of
      double-balloon enteroscopy (DBE), which is expected to make full-length
      enteroscopy possible. PATIENTS AND METHODS: Between November 2003 and May 2005,
      double-balloon enteroscopy was conducted in 275 consecutive patients presenting
      at two tertiary referral hospitals. The characteristics of the patients,
      indications for the procedures, procedural parameters, and diagnostic yield are
      described here. All conventional treatment options were available. The
      tolerability of the procedure was assessed in a small subset of the patients.
      After the procedure, the patients were monitored in a recovery room for at least
      2h. They were discharged afterwards, provided there were no signs of
      complications or complaints. RESULTS: The main indication for DBE was suspected
      small-bowel bleeding (n=168), and the lesions responsible for the bleeding were
      found in 123 patients (73 %) and treated in 61 (55 %). In patients with
      refractory celiac disease (n=25), DBE revealed a high proportion (six patients,
      23 %) of enteropathy-associated T-cell lymphomas that had not been suspected on
      other tests. Further DBE indications were surveillance and treatment of
      hereditary polyposis syndromes (n=20); and suspected Crohn's disease, which was
      diagnosed with DBE in four of 13 patients (30 %). No relevant pathology was found
      in 24 % of the patients. Panenteroscopy was successfully performed in 26 of 62
      patients (42 %) in whom it was attempted, in either one or two sessions. The
      average duration of the procedures was 90 min (range 30 - 180 min, SD 42), and
      the average insertion length was 270 cm (range 60 - 600 cm, SD 104). Patients'
      tolerance of the procedure was excellent. Severe complications were recognized in
      three cases (1 %), all involving pancreatitis. CONCLUSIONS: This large pilot
      series shows that DBE is a well-tolerated and safe new endoscopic technique with
      a high diagnostic yield in selected patients.

PMID- 16429355
TI  - Outcome of capsule endoscopy in determining indication and route for push-and
      pull enteroscopy.
AB  - BACKGROUND AND STUDY AIM: Video capsule endoscopy and push-and-pull enteroscopy
      (PPE), both allow a complete examination of the small bowel in patients with
      suspected intestinal disorders. Due to the invasiveness of PPE, indications
      should probably be selective. The aim of the present prospective study was to
      evaluate the outcome of an approach whereby capsule endoscopy was used to select
      patients in whom PPE was indicated. PATIENTS AND METHODS: 164 patients were
      included (90 men; age 54+/-18 years) with various indications for small-bowel
      investigation, such as obscure bleeding (n=88), suspected Crohn's (n=14) or
      celiac (n=12) disease, or known or strongly suspected localized diseases such as
      neoplasms (n = 18) for biopsy. Four patients with a suspected intestinal stenosis
      underwent PPE without prior capsule endoscopy. In the remaining 160 patients, who
      had a capsule endoscopy, PPE was selected if there were lesions requiring biopsy
      or angiodysplasias to be treated by argon plasma coagulation (APC). Regarding the
      insertion route, an anal PPE was indicated if the capsule transit time from
      ingestion to arrival at the lesion was >or= 75 % of the total time from ingestion
      to arrival at the cecum. After gut cleansing, PPE was performed with general
      anesthesia, and the small bowel was examined until the lesion was reached or the
      scope could not be advanced further. If the suspected lesion had not been
      reached, a second procedure was performed through the alternative route, under
      the same conditions. RESULTS: The diagnostic yield of capsule endoscopy was 75 %.
      According to the indications, 47 PPE procedures were performed in 42 patients,
      including 33 through the oral route, 4 through the anal route and 5 combined
      ones. Indications were: suspicion of intestinal tumor (n=13), celiac disease with
      chronic bleeding (n=4), suspicion of Crohn's disease (n=3), treatment of
      significant arteriovenous malformations (AVMs) (n=10), diffuse enteropathies
      (n=3), nonsteroidal anti-inflammatory drug (NSAID)-related conditions (n=2), and
      obscure digestive bleeding (n=3). Lesions detected by capsule endoscopy were
      reached by PPE in all but two cases. The positive predictive value (PPV) of
      capsule endoscopy to make a correct indication for PPE was 94.7 % and the
      negative predictive value (NPV) was 98.3 %. The PPV and NPV of a time index of >
      0.75 to start via the anal route were 94.7 % and 96.7 %. No complications were
      observed and all patients were discharged the day after the procedure. Follow-up
      at 9 months showed that capsule endoscopy followed by PPE had positively
      influenced the management of 90.5 % of the patients. CONCLUSIONS: The use of
      capsule endoscopy as a filter for PPE results in effective management of patients
      with various intestinal diseases. Capsule endoscopy can also direct the choice of
      route of PPE; a time index of > 0.75 appears to reliably indicate an anal route
      so that a double procedure is required in only about 12 % of cases.

PMID- 16429356
TI  - Preliminary comparison of capsule endoscopy and double-balloon enteroscopy in
      patients with suspected small-bowel bleeding.
AB  - BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) and double-balloon enteroscopy
      (DBE) have been introduced as modalities for examining the entire small bowel.
      The aim of the present study was to assess the clinical effects of CE and DBE to
      consider the roles of CE and DBE and the indications for the procedures in
      patients with suspected small-bowel bleeding. PATIENTS AND METHODS: Between June
      2004 and January 2005, 32 patients in whom a site of bleeding in the
      gastrointestinal tract had not been identified were enrolled in the study. Twenty
      eight patients were examined with both methods. Bleeding sources were categorized
      as either A1 lesions (immediate hemostatic procedures required) or A2 lesions
      (close observation required). CE and DBE were evaluated with regard to whether or
      not they were capable of accessing the entire small bowel and provided a
      diagnosis, and the access and diagnostic rates were calculated. RESULTS: On CE,
      13 patients were diagnosed with A1 lesions and six with A2 lesions; on DBE, 11
      had A1 lesions and one had an A2 lesion. The access rate for the entire small
      intestine on CE was 90.6 % (29 of 32), significantly higher than with DBE at 62.5
      % (10 of 16; P < 0.05). The diagnostic rate on CE was 59.4 % (19 of 32), higher
      than with DBE at 42.9 % (12 of 28; P = 0.30), but not significantly different.
      Among patients with A1 lesions who were diagnosed with DBE, histological
      diagnoses were obtained in six of the 11, and three patients were treated.
      CONCLUSIONS: In many suspected small-bowel bleeding cases, CE should be selected
      for the initial diagnosis and DBE for treatment or histopathological diagnosis
      after detection of the bleeding site on CE.

PMID- 16429358
TI  - Mid-gastrointestinal bleeding: capsule endoscopy and push-and-pull enteroscopy
      give rise to a new medical term.

PMID- 16429357
TI  - Diagnostic and therapeutic impact of double-balloon enteroscopy.
AB  - BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a new endoscopic
      method for examining the small intestine. Most reports of DBE have been from
      Japan, and very few data on this new technique have been reported by centers
      outside Japan. The aim of the present study was to determine the diagnostic yield
      of DBE, measure the frequency of management changes made on the basis of the
      results, and evaluate the clinical outcome for patients undergoing the procedure.
      PATIENTS AND METHODS: All patients undergoing DBE using a Fujinon enteroscope
      (length 200 cm, diameter 8 mm) during a 11-month period were studied. All of the
      patients had previously undergone esophagogastroduodenoscopy and colonoscopy.
      They underwent small-bowel cleansing on the day before the procedure using a
      standard colon lavage solution. RESULTS: Seventy DBE procedures were carried out
      in 53 patients (34 men, 19 women; mean age 60 years, range 24 - 80) by the oral
      route in 46 cases and the anal route in 24. The indications for the examination
      were gastrointestinal bleeding (n = 29), suspected Crohn's disease (n = 6),
      abdominal pain (n = 4), polyp removal or evaluation in polyposis syndromes (n =
      6), chronic diarrhea (n = 4), and surveillance or tumor search (n = 4). The mean
      duration of the procedure was 72 min (range 25 min - 3 h). The mean radiation
      exposure was 441 dGy/cm (range 70 - 1462), and the mean depth of small-bowel
      insertion was 150 cm (range 1 - 470 cm). It was possible to evaluate the entire
      small bowel in four patients (8 %). A new diagnosis was obtained in 26 of the 53
      patients (49 %). The findings in the 70 procedures were angiodysplasia (n = 13),
      ulcerations or erosions (n = 5), jejunitis or ileitis (n = 5), tumors (n = 5),
      stenosis (n = 4), polyps (n = 5), lymphangiectasias (n = 4), Crohn's disease (n =
      4), and normal (n = 17). DBE resulted in a therapeutic intervention (endoscopic,
      medical or surgical, excluding blood transfusions) in 57 % of the patients (30 of
      53). The only complication (1.4 %) observed was one case of intraprocedural
      postpolypectomy bleeding, which resolved with injection of epinephrine.
      CONCLUSION: In almost two-thirds of the patients examined, DBE was clinically
      useful for obtaining a new diagnosis and starting new treatments, changing
      existing treatments, carrying out surgical intervention, or providing therapeutic
      endoscopy. DBE is a useful and safe method of obtaining tissue for diagnosis,
      providing hemostasis, and carrying out polypectomy.

PMID- 16429359
TI  - Narrow-band imaging: potential and limitations.
AB  - The purpose of introducing optical electronics into video endoscopes is to
      improve the accuracy of diagnosis through image processing and digital
      technology. Narrow-band imaging (NBI), one of the most recent techniques,
      involves the use of interference filters to illuminate the target in narrowed
      red, green and blue (R/G/B) bands of the spectrum. This results in different
      images at distinct levels of the mucosa and increases the contrast between the
      epithelial surface and the subjacent vascular network. NBI can be combined with
      magnifying endoscopy with an optical zoom. The aim of this new technique is to
      characterize the surface of the distinct types of gastrointestinal epithelia - e.
      g., intestinal metaplasia in Barrett's esophagus. The technique may also make it
      possible to demonstrate disorganization of the vascular pattern in inflammatory
      disorders of the gastrointestinal mucosa and in superficial neoplastic lesions in
      the esophagus, stomach, and large bowel.

PMID- 16429360
TI  - Acute pancreatitis after double-balloon enteroscopy: an old pathogenetic theory
      revisited as a result of using a new endoscopic tool.
AB  - Double-balloon enteroscopy is a novel technique for visualizing the entire small
      bowel. Complications have been reported relatively rarely in the small series
      published up until now. In this report we describe two patients who developed
      acute pancreatitis immediately after double-balloon enteroscopy, diagnosed on
      clinical, biochemical, and radiological grounds. In both patients the
      pancreatitis resolved with supportive care. Based on early studies on the
      pathogenesis of acute pancreatitis, we discuss the possible pathogenetic
      mechanism for pancreatitis arising as a complication of this novel endoscopic
      technique.

PMID- 16429361
TI  - A new technique of endoscopic full-thickness resection using a flexible stapler.
AB  - There is a significant need for a safe and easy technique for endoluminal
      endoscopic resection of gastrointestinal lesions, but such procedures are usually
      restricted to resection of the mucosal layer in order to preserve the integrity
      of the wall of the gastrointestinal tract. We present two patients, one with
      early cancer and one with a carcinoid tumor, who were treated by endoscopic full
      thickness resection. We used a stapling device, consisting of a flexible shaft,
      which was positioned intraluminally, and a remote control. After pilot
      investigations in pigs and in human anatomical preparations, we performed a full
      thickness resection of the gastric wall in these patients, using the flexible
      stapling device under gastroscopic control. Gastric wall specimens up to 4 cm x 4
      cm in size were resected with the use of two to three stapler magazines. Both
      procedures followed an uneventful course and the patients made an uncomplicated
      recovery. Further studies are necessary to test the applicability of the
      technique in the management of other gastric neoplastic lesions.

PMID- 16429362
TI  - Obstructive jaundice due to isolated tuberculosis of the pancreas: endoscopic
      treatment instead of surgery?
AB  - The optimal treatment for relieving biliary obstruction due to isolated
      pancreatic tuberculosis has not so far been defined, and most previously reported
      patients were treated surgically. We describe a 17-year-old, immunocompetent girl
      who was admitted with obstructive jaundice caused by a tuberculous mass in the
      head of the pancreas. Antituberculous therapy alone failed to alleviate the
      jaundice, and she was therefore treated by stent insertion and, subsequently,
      balloon dilation of the common bile duct stricture. At follow-up 5 years later,
      magnetic resonance cholangiopancreatography showed no evidence of stricture in
      the common bile duct.

PMID- 16429363
TI  - Gastrostomy - seeing beyond the endoscope.

PMID- 16429365
TI  - Lack of reciprocal interference between capsule endoscope and left ventricular
      assist device.

PMID- 16429367
TI  - Value of endoscopic marking of the z-line for detecting short esophagus before
      repeat surgery for recurrent paraesophageal hernias.

PMID- 16429368
TI  - A single therapeutic echo endoscope used for combined transgastric and
      transpapillary drainage of a pancreatic abscess.

PMID- 16429369
TI  - Collagen/povidone as a new endoscopic treatment option in peptic ulcer bleeding.

PMID- 16429370
TI  - Adaptation of the Erlangen Active Simulator for Interventional Endoscopy (EASIE)
      model for transmural pancreatic pseudocyst drainage.

PMID- 16429371
TI  - Endoscopic resection of ampullary carcinoma.

PMID- 16429372
TI  - The Olympus EVIS LUCERA variable indices of haemoglobin chart function: a novel
      technique for establishing the completeness of vascular mucosal ablation in
      colonic angiodysplasia.

PMID- 16429374
TI  - Juvenile limb-girdle myasthenia gravis.
AB  - Limb-girdle myasthenia is a rare disorder which includes familial and autoimmune
      forms. Myasthenia gravis is an uncommon disease in children and its diagnosis may
      be difficult. We report here five cases of autoimmune juvenile LGM starting
      before the age of 16 years with attention to clinical diagnostic difficulties,
      evolution, laboratory and instrumental data as well as response to treatment.
      Diagnosis of limb-girdle myasthenia requires a strong index of suspicion also in
      childhood. We suggest that this form be suspected in children with unclassifiable
      myopathy, mostly affecting deltoid muscles and lower extremities.

PMID- 16429375
TI  - Outcome of medulloblastoma in children: long-term complications and quality of
      life.
AB  - To study the outcomes in long-term survivors of paediatric medulloblastoma (MB),
      we followed 51 consecutive children who were treated between 1980 and 2000 in a
      single institution. In 18 of 26 survivors (mean follow-up time 12.2 years),
      tumour control, neurological, endocrine, and neurocognitive complications and
      their impact on behavioural and psychological adjustment, and health-related
      quality of life (QoL) were comprehensively assessed using qualitative and
      quantitative measures. Endocrine deficits occurred in 61 %, neurological
      complications in 72 %, and significant school problems in 72 %. All patients had
      significant deficits in neurocognitive functioning: attention and processing
      speed was impaired in 79 %, learning and memory in 88 %, language in 56 %, visual
      perception in 50 %, and executive functions in 64 %. In comparison with healthy
      controls, social functioning was rated by the patients as the QoL dimension most
      affected. Parents' ratings were considerably lower than those of the patients. No
      MB survivor > 18 years of age (n = 12) had a boy- or girlfriend. Because of their
      treatment, including craniospinal radiotherapy, MB long-time survivors are not
      only at great risk for neurological, endocrine, and neurocognitive complications,
      but also of social isolation thereby decreasing self-rated QoL substantially.

PMID- 16429376
TI  - MRI and 1H-MRS findings in early-onset cobalamin C/D defect.
AB  - OBJECT: Cobalamin C/D defect is an inborn error of cobalamin metabolism causing
      methylmalonic aciduria and homocystinuria. The early-onset form is characterized
      by severe neurological impairment. The aim of this study was to evaluate and
      monitor brain damage in early-onset cbl-C/D defect by conventional MRI and to
      assess the additional value of 1H-MRS. METHODS: We retrospectively examined
      serial MRI studies of 7 patients, performed on a 1.5 T system. Four patients had
      the first evaluation within the first 4 months of life and three later. The
      imaging protocol included spin-echo T1-weighted, T2-weighted, IR, and FLAIR. Five
      patients underwent 1H-MRS, using chemical shift imaging (CSI) in three patients
      and single voxel spectroscopy (SVS) in two. RESULTS: Three of the patients
      studied early showed tetraventricular hydrocephalus and diffuse swelling of
      supratentorial white matter with involvement of the "U" fibres. Two showed patchy
      cavitating lesions in the basal ganglia. White matter changes became evident at a
      later stage. In three cases 1H-MRS showed an abnormal peak of lactate in the
      basal ganglia or in the periventricular white matter. CONCLUSIONS: Our study
      shows severe heterogeneous brain MR abnormalities in cbl-C/D defect. We observed
      unusual basal ganglia lesions in 30 % of our cases and also found a high
      incidence of hydrocephalus and supratentorial white matter abnormalities.

PMID- 16429377
TI  - Recruitment of the sensorimotor cortex--a developmental FMRI study.
AB  - INTRODUCTION: The growing mastery of motor tasks is one of the most visible
      changes in the developing child. The cortex is known to play a central role in
      learning, planning, and performance of motor tasks. We investigated the age
      dependency of motor cortex activation using functional magnetic resonance imaging
      (fMRI). METHODS: Thirty-two right-handed subjects were studied: 11 children
      (median age 9 years, range 6 - 10 years), 10 adolescents (median age 13 years,
      range 11 - 15 years), and 11 adults (median age 27 years, range 23 - 42 years).
      The subjects performed a simple, paced unilateral motor task (repetitive
      squeezing of a ball with the right hand). Also, we set up a control experiment
      (visual stimulation using an alternating checkerboard pattern) in which no age
      related differences were expected. RESULTS: Compared to children, adults showed
      significantly increased activation of the bilateral sensorimotor cortex, parietal
      areas, the supplementary motor area, and the cerebellum. In the visual
      stimulation experiment there were no age-related differences. CONCLUSION:
      Children show a significant difference in the degree of cortical activation
      compared to adults when performing a simple motor task. The change in fMRI
      activation patterns may reflect a maturation process of primary and secondary
      motor areas.

PMID- 16429378
TI  - Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett
      syndrome: treatment with folinic acid.
AB  - BACKGROUND: Previous studies in Rett syndrome (RS) patients suggested various
      abnormalities in biogenic amines, pterins, and folate values in cerebrospinal
      fluid (CSF). Our aim was to analyse these metabolites in CSF of 16 RS patients
      (age range: 2 - 23 years). Biogenic amines, pterins, and 5-methyltetrahydrofolate
      were measured by HPLC with electrochemical and fluorescence detection. RESULTS:
      CSF values of 5-methyltetrahydrofolate were decreased in 8 out of 16 RS patients
      (average: 53.6 nmol/L; range: 19 - 92) when compared with our reference values
      (average: 74.6 nmol/L; range: 45 - 127). These eight patients had epilepsy, while
      4 out of 16 RS patients who did not have epilepsy showed normal CSF 5
      methyltetrahydrofolate concentrations. Values of biogenic amines or pterins were
      decreased in four of the patients with low values of 5-methyltetrahydrofolate. No
      correlation was observed between CSF values of 5-methyltetrahydrofolate and
      pterins, biogenic amines, or age. Supplementation with folinic acid was applied
      in six out of the eight patients with CSF 5-methyltetrahydrofolate deficiency. An
      improvement was noticed in all cases. CONCLUSIONS: An important percentage of RS
      patients showed 5-methyltetrahydrofolate concentrations under the reference
      values. Therefore, analysis of CSF 5-methyltetrahydrofolate seems advisable in
      RS, especially in patients with epilepsy and those resistant to antiepileptic
      drugs.

PMID- 16429379
TI  - Autoantibodies to human manganese superoxide dismutase (MnSOD) in children with
      facial palsy due to neuroborreliosis.
AB  - AIM: Acute peripheral facial palsy due to neuroborreliosis is associated with a
      distal neuritis. In patients with Lyme disease the activity of antioxidant
      enzymes is decreased. With respect to the pathogenesis of neuroborreliosis, sera
      of children with acute peripheral facial palsy were investigated for
      autoantibodies against human manganese superoxide dismutase (MnSOD), which were
      suspected of raising the oxidative injury of infected tissues. METHODS: Sera of
      20 children with acute peripheral palsy with neuroborreliosis, sera of 20
      children with facial palsy without reference to Lyme disease and sera of 14 blood
      donors were tested for antibodies against human MnSOD using an ELISA. RESULTS:
      The concentrations of IgM autoantibodies to MnSOD of the children with
      neuroborreliosis were significantly increased, compared with the two control
      groups. CONCLUSIONS: We propose that the antibodies detected block the protective
      effects of MnSOD resulting in an increased oxidative inflammation.

PMID- 16429380
TI  - Molybdenum cofactor deficiency presenting as neonatal hyperekplexia: a clinical,
      biochemical and genetic study.
AB  - We report a newborn with exaggerated startle reactions and stiffness of neonatal
      onset, the prototypical signs of hyperekplexia. Startle and flexor spasms,
      leading to apnoea, did not respond to treatment with clonazepam but did partially
      to sodium valproate. Molecular analysis of GLRA1 revealed no mutations. The
      incidental finding of hypouricemia led to a work-up for molybdenum cofactor
      (MoCo) deficiency; the diagnosis was confirmed by the altered urine chemistries,
      including elevated urine S-sulphocysteine. Despite persistence of the spasms,
      clinical or electrographic seizures were never detected before the infant died at
      age 1 month. In this patient, the concurrence of hyperekplexia and MoCo
      deficiency was suggestive of impaired gephyrin function. GPH mutational analysis,
      however, showed no abnormalities. The patient was eventually found to harbour a
      novel c.1064T > C mutation in exon 8 of the MOCS1 gene. Despite extensive
      sequence analysis of the gene, the second causative mutation of this recessive
      trait still awaits identification. MoCo deficiency should be considered in the
      differential diagnosis of neonatal hyperekplexia, particularly in the instances
      of refractoriness to clonazepam, an early demise in infancy or the evidence of no
      mutations in the GLRA1 gene.

PMID- 16429382
TI  - Phenotypic overlap between infantile systemic lupus erythematosus and Aicardi
      Goutieres syndrome.

PMID- 16429381
TI  - Oculomotor nerve schwannoma mimicking ophthalmoplegic migraine.
AB  - Ophthalmoplegic migraine (OM) is a rare variant of migraine characterized by
      recurrent attacks of severe headache followed by oculomotor nerve palsy. The
      recent revision of the International Headache Classification has reclassified OM
      from a subtype of migraine, defined as a functional headache, to the neuralgia
      category. We describe a case of an 11-year-old girl with pathologically confirmed
      oculomotor nerve schwannoma who had been suffering from symptoms mimicking OM.
      For five years, she has been under treatment for OM, an initial diagnosis which
      was corroborated by brain magnetic resonance imaging (MRI). Usually, most OM
      attacks occur during one period in a lifetime and remit completely. In contrast,
      however, her attacks became more frequent and were not controlled by medication.
      After surgery, the frequency of OM attacks was reduced. From this experience, we
      hypothesize that optic nerve tumor is one condition that can mimic OM, without
      apparent signs suggestive of intracranial mass. To our knowledge, this is the
      first report to describe a pathologically confirmed case of oculomotor nerve
      schwannoma mimicking OM.

PMID- 16429388
TI  - [Transbronchial biopsy in comparison with catheter aspiration in the diagnosis of
      peripheral pulmonary nodules].
AB  - BACKGROUND: Usually, transbronchial biopsy (TBB) is performed in the evaluation
      of bronchoscopically invisible solitary nodules and peripheral lesions of the
      lung. Additionally catheter aspiration can be done with the fiberbronchoscope,
      also under fluoroscopic guidance, to get cytological material. Despite of its
      simplicity, the catheter aspiration technique is widely unknown. METHOD: In a
      prospective study we compared the diagnostic yield of both procedures concerning
      malignancy. 28 consecutive patients (age 69.4 +/- 8.9 years) underwent both TBB
      and catheter aspiration. RESULTS: The tumor size measured 41.4 +/- 14.5 mm. The
      frequency of TBB was 3.4 +/- 1.8 and of catheter aspiration 2.6 +/- 1.2 per
      patient. A malignant tumor was diagnosed in 13 cases by TBB and in 20 cases by
      catheter aspiration. With the combination of both methods, a malignancy was
      diagnosed in 23 cases. 3 of 5 bronchoscopically not malignant tumors turned out
      to be bronchial cancer by surgery, the other 2 were benign in a 2 year follow up.
      CONCLUSION: The diagnostic yield of catheter aspiration is significantly superior
      to transbronchial biopsy (77 % compared with 50 %, p < 0.05 chi square test).
      When combining both methods the result is further improved by about 10 %.
      Composed to of other cytological methods (transbronchial needle aspiration, brush
      cytology) aspiration by catheter seems at least comparable, but with cost saving
      advantages.

PMID- 16429389
TI  - [Acute exacerbation of COPD].

PMID- 16429390
TI  - [Interferon-gamma assays -- description and assessment of a new tool in the
      diagnosis of tuberculosis].
AB  - Up to now the diagnosis of latent tuberculosis infection (LTBI) was based solely
      on the tuberculin skin test. However, this method offers neither 100 %
      sensitivity nor -- and this is in particular due to its cross-reactivity with BCG
      and environmental mycobacteria -- a 100 % specificity. The demand in Germany for
      a more reliable in vitro test is currently enhanced by the change from the
      multipuncture test to the intradermal (Mendel-Mantoux) test and by the
      uncertainty resulting from the ceased production of the tuberculin previously
      used in Germany. The manufacturers of immunologic test methods such as the
      QuantiFERON-TB Gold In-Tube (ELISA assay) and the T SPOT-TB Test (ELISPOT assay),
      which are based on the Interferon-gamma (IFN-gamma) production of sensitized T
      lymphocytes, offer their products as possible alternatives. This article explains
      the function of the IFN-gamma tests and gives an overview of the most recent
      data, possible indications and the open scientific questions to be investigated
      by future clinical studies. Although the new test methods have the potential to
      eventually prevail as an additional helpful diagnostic tool, the authors consider
      a complete replacement of the tuberculin skin test as premature. The IFN-gamma
      tests may, however, prove already now to be a useful additional diagnostic
      method.

PMID- 16429392
TI  - [Curriculum pneumologicum 2005. Part 1].

PMID- 16429391
TI  - [Bronchoscopy 2005].

PMID- 16429393
TI  - High frequency of beta-catenin mutations in borderline endometrioid tumours of
      the ovary.
AB  - Some low-grade endometrioid carcinomas arise from a background of endometrioid
      tumours of borderline malignancy. To determine the molecular mechanisms involved
      in the initiation of endometrioid carcinoma, the present study investigated
      whether the genetic alterations reported in these tumours (mutations in PTEN,
      KRAS, and beta-catenin genes, and microsatellite instability) are already present
      in endometrioid tumours of borderline malignancy. Eight endometrioid tumours of
      borderline malignancy were studied. By immunohistochemistry, beta-catenin was
      expressed in the nuclei of all tumours, suggesting the presence of stabilizing
      beta-catenin mutations. By mutational analysis, five different beta-catenin
      mutations were found in seven of eight cases (90%), affecting codons 32, 33, and
      37. In contrast, only one tumour harboured a PTEN mutation, which affected codon
      130. Neither KRAS mutations nor microsatellite instability was detected. A review
      of the literature indicated that beta-catenin mutations are characteristic of
      well-differentiated endometrioid carcinomas, since they were present in nearly
      60% of grade I but in less of 3% of grade III tumours. In conclusion, the present
      study identifies beta-catenin mutation as a nearly constant molecular alteration
      in borderline endometrioid tumours, whereas PTEN and KRAS mutations and
      microsatellite instability are very infrequent. The findings in the present
      study, and previously reported data, strongly suggest that beta-catenin mutation
      is an early event in endometrioid ovarian carcinogenesis, and that it is involved
      in the development of low-grade endometrioid tumours.

PMID- 16429394
TI  - Morphological and immunophenotypic analysis of breast carcinomas with basal and
      myoepithelial differentiation.
AB  - The aim of this study was to assess the morphological characteristics and
      immunohistochemical profile of breast carcinomas with basal and myoepithelial
      phenotypes to obtain a better understanding of their biological behaviour and
      nature. One thousand nine hundred and forty-four invasive breast carcinomas were
      examined, using tissue microarray (TMA) technology and immunohistochemistry, to
      identify those tumours that showed basal and myoepithelial phenotypes, and their
      immunophenotype profile was characterized using a variety of markers. In
      addition, haematoxylin and eosin-stained sections of these tumours were studied
      for several morphological parameters. The findings were correlated with patient
      and tumour characteristics and outcome data. Tumours were classified into two
      groups: (1) tumours with basal phenotype [expressing one or both basal markers
      (CK5/6 and/or CK14)] and (2) tumours with myoepithelial phenotype (expressing SMA
      and/or p63). Group 1 was further subdivided into two subgroups: (A) dominant
      basal pattern (more than 50% of cells positive) and (B) basal characteristics (10
      50% of cells positive). Group 1 tumours constituted 18.6% (8.6% and 10% for
      groups 1A and 1B, respectively) and group 2 constituted 13.7% of the cases. In
      both groups, the most common histological types were ductal/no specific type,
      tubular mixed and medullary-like carcinomas; the majority of these tumours were
      grade 3. There were positive associations with adenoid cystic growth pattern,
      loss of tubule formation, marked cellular pleomorphism, poorer Nottingham
      prognostic index, and development of distant metastasis. In addition,
      associations were found with loss of expression of steroid hormone receptors and
      FHIT proteins and positive expression of p53 and EGFR. The most common
      characteristics in group 1 were larger size, high-grade comedo-type necrosis,
      development of tumour recurrence, and absence of lymph node disease. Group 2
      tumours were more common in younger patients and were associated with central
      acellular zones, basaloid change, and positive E-cadherin protein expression.
      Group 1 characteristics were associated with both reduced overall survival (OS)
      [log rank (LR) = 22.5, p < 0.001] and reduced disease-free interval (DFI) (LR =
      30.1, p < 0.001), while group 2 characteristics showed an association with OS (LR
      = 5, p = 0.02) but not with DFI. Multivariate analysis showed that basal, but not
      myoepithelial, phenotype has an independent value in predicting outcome. Breast
      cancers with basal and myoepithelial phenotypes are distinct groups of tumours
      that share some common morphological features and an association with poor
      prognosis. The basal rather than the myoepithelial phenotype has the strongest
      relationship with patient outcome.

PMID- 16429395
TI  - Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is clinically characterized by a sustained
      elevation in mean pulmonary artery pressure leading to significant morbidity and
      mortality. The disorder is typically sporadic, and in such cases the term
      idiopathic PAH (IPAH) is used. However, cases that occur within families
      (familial PAH (FPAH)) display similar clinical and histopathological features,
      suggesting a common etiology. Heterozygous mutations of a type II member of the
      TGF-beta cell signaling superfamily known as BMPR2 on chromosome 2q33 have been
      identified in many kindreds with FPAH, yet display both reduced penetrance and
      sex bias. This report presents the compilation of data for 144 distinct mutations
      that alter the coding sequence of the BMPR2 gene identified in 210 independent
      PAH subjects. This large data set characterizes the extent of sequence variation
      and reveals that the majority (71%) of mutations in FPAH and IPAH comprise
      nonsense, frameshift, and splice-site defects, and gene rearrangements. These
      predict premature termination of the transcript with likely loss through the
      process of nonsense-mediated decay (NMD). A total of 44 missense mutations were
      identified that substitute amino acid residues at highly conserved sites within
      recognized functional domains of the mature receptor. We assess this category of
      mutations in the context of their heterogeneous effects on cell signaling when
      assayed by in vitro cell-based systems. Disease-causing mutation hot-spots within
      BMPR2 are summarized. Taken together, these observations are likely to aid in the
      development of targeted mutation detection strategies relevant for patient
      management. Finally, we examine the age- and sex-dependent reduced penetrance of
      BMPR2 mutations by reviewing bmpr2 animal models and the requirement for
      additional genetic and/or environmental modifiers of disease. In conclusion,
      these data provide compelling genetic evidence that haploinsufficiency is the
      predominant molecular mechanism underlying disease predisposition, and support
      the concept of a critical threshold of signaling activity below which disease may
      be precipitated.

PMID- 16429396
TI  - Paternal uniparental isodisomy of the entire chromosome 3 revealed in a person
      with no apparent phenotypic disorders.
AB  - Uniparental disomy (UPD) is a rare genetic abnormality. During a whole genome
      linkage study we identified a case of paternal uniparental isodisomy 3
      serendipitously. This is the first ascertained human paternal UPD for chromosome
      3 (UPD3pat). The finding of this paternal UPD case of the entire chromosome 3
      with no apparent phenotypic disorders suggests that there are no paternal
      imprinted genes causing rare genetic disorders on chromosome 3.

PMID- 16429397
TI  - Degree of blockiness of amide groups as indicator for difference in physical
      behavior of amidated pectins.
AB  - Thickening and gelling properties of commercial amidated pectins depend on the
      degree of amidation and methyl-esterification, but also the distribution of these
      groups is of great importance. Methods have been developed during the last few
      years to determine the distribution of methyl esters over the pectic backbone. We
      applied the strategies developed for the analysis of high methyl-esterified
      pectins for studying the distribution of amide groups in amidated pectins. Low
      methyl-esterified amidated (LMA) pectins were digested before and after removal
      of methyl esters by an endo-polygalacturonase to determine the degree of
      blockiness of the substituents. The nature of the substituents (amide groups
      compared to methyl esters) did not modify the behavior of the enzyme. Oligomers
      released were separated by using high-performance anion exchange chromatography
      and pulsed amperometric detection (HPAEC-PAD) at pH 5. Fractions collected after
      on-line desalting were identified by using MALDI-TOF mass spectrometry. Oligomers
      were found to elute from the column as a function of their total charge. For the
      same overall charge and size, oligomers with methyl esters eluted before
      oligomers with amide groups. Both amide groups and methyl esters of the LMA
      pectins studied were found to be semirandomly distributed over the pectic
      backbone, but this may vary according to the amidation process used.

PMID- 16429399
TI  - Nonsynonymous SNPs: validation characteristics, derived allele frequency
      patterns, and suggestive evidence for natural selection.
AB  - We experimentally investigated more than 1,200 entries in dbSNP that would change
      amino-acids (nsSNPs), using various subsets of DNA samples drawn from 18 global
      populations (approximately 1,000 subjects in total). First, we mined the data for
      any SNP features that correlated with a high validation rate. Useful predictors
      of valid SNPs included multiple submissions to dbSNP, having a dbSNP validation
      statement, and being present in a low number of ESTs. Together, these features
      improved validation rates by almost 10-fold. Higher-abundance SNPs (e.g., T/C
      variants) also validated more frequently. Second, we considered derived alleles
      and noted a considerably (approximately 10%) increased average derived allele
      frequency (DAF) in Europeans vs. Africans, plus a further increase in some other
      populations. This was not primarily due to an SNP ascertainment bias, nor to the
      effects of natural selection. Instead, it can be explained as a drift-based,
      progressive increase in DAF that occurs over many generations and becomes
      exaggerated during population bottlenecks. This observation could be used as the
      basis for novel DAF-based tests for comparing demographic histories. Finally, we
      considered individual marker patterns and identified 37 SNPs with allele
      frequency variance or FST values consistent with the effects of population
      specific natural selection. Four particularly striking clusters of these markers
      were apparent, and three of these coincide with genes/regions from among only
      several dozen such domains previously suggested by others to carry signatures of
      selection.

PMID- 16429400
TI  - A rare missense mutation in a type 2 diabetes patient decreases the
      transcriptional activity of human sterol regulatory element binding protein-1.
AB  - Sterol regulatory element binding protein 1 (SREBP-1) transcription factors play
      a key role in energy homeostasis by regulating genes involved in both
      carbohydrate and lipid metabolism, and in adipocyte differentiation. The 5' end
      of the mRNA-encoding SREBP-1 exists in two forms, designated 1a and 1c. The
      divergence results from the use of two transcription start sites that produce two
      separate 5' exons, each of which is spliced to a common exon 2. Mutations in the
      sterol regulatory element binding protein gene (SREBF)-1 may contribute to
      insulin resistance states. However, the variants described to date do not affect
      the SREBP function. In this study, we investigated the functional consequences of
      a novel missense mutation common to both SREBP-1 isoforms identified in a Spanish
      type 2 diabetic patient (c.677C>T, SREBP-1a p.T226M; c.605C>T, SREBP-1c p.T202M).
      Using reporter gene analysis and electrophoretic mobility shift assays, we found
      that this variant impairs the transcriptional activity and reduces DNA binding
      ability despite its comparable protein stability to the wild-type SREBP-1. This
      decreased activity impairs the expression of known downstream targets, such as
      the LDL receptor and fatty acid synthase genes. Our findings suggest that the
      threonine residue and/or surrounding region play an important role in the SREBP-1
      function.

PMID- 16429401
TI  - Detection of heterozygous SALL1 deletions by quantitative real time PCR proves
      the contribution of a SALL1 dosage effect in the pathogenesis of Townes-Brocks
      syndrome.
AB  - Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited disorder
      characterized by ear, anal, limb, and renal malformations, and results from
      mutations in the gene SALL1. All SALL1 mutations previously found in TBS patients
      create preterminal termination codons. In accordance with the findings of
      pericentric inversions or balanced translocations, TBS was initially assumed to
      be caused by SALL1 haploinsufficiency. This assumption was strongly contradicted
      by a Sall1 mouse knock-out, because neither hetero- nor homozygous knock-out
      mutants displayed a TBS-like phenotype. A different mouse mutant mimicking the
      human SALL1 mutations, however, showed a TBS-like phenotype in the heterozygous
      situation, suggesting a dominant-negative action of the mutations causing TBS. We
      applied quantitative real time PCR to detect and map SALL1 deletions in 240
      patients with the clinical diagnosis of TBS, who were negative for SALL1
      mutations. Deletions were found in three families. In the first family, a 75 kb
      deletion including all SALL1 exons had been inherited by two siblings from their
      father. A second, sporadic patient carried a de novo 1.9-2.6 Mb deletion
      including the whole SALL1 gene, and yet another sporadic case was found to carry
      an intragenic deletion of 3384 bp. In all affected persons, the TBS phenotype is
      rather mild as compared to the phenotype resulting from point mutations. These
      results confirm that SALL1 haploinsufficiency is sufficient to cause a mild TBS
      phenotype but suggest that it is not sufficient to cause the severe, classical
      form. It therefore seems that there is a different contribution of SALL1 gene
      function to mouse and human embryonic development.

PMID- 16429398
TI  - Heat capacity changes associated with nucleic acid folding.
AB  - Whereas heat capacity changes (DeltaCPs) associated with folding transitions are
      commonplace in the literature of protein folding, they have long been considered
      a minor energetic contributor in nucleic acid folding. Recent advances in the
      understanding of nucleic acid folding and improved technology for measuring the
      energetics of folding transitions have allowed a greater experimental window for
      measuring these effects. We present in this review a survey of current literature
      that confronts the issue of DeltaCPs associated with nucleic acid folding
      transitions. This work helps to gather the molecular insights that can be gleaned
      from analysis of DeltaCPs and points toward the challenges that will need to be
      overcome if the energetic contribution of DeltaCP terms are to be put to use in
      improving free energy calculations for nucleic acid structure prediction.

PMID- 16429402
TI  - Functional assays testing pathogenicity of 14 cystathionine-beta synthase
      mutations.
AB  - In this study, 14 CBS alleles from homocystinuric patients were expressed
      heterologously in E. coli and their enzyme activities were assayed in vitro.
      Additionally, mutant CBS proteins were visualized by Western blot from denaturing
      and non-denaturing polyacrylamide gels. The 14 mutations characterized were:
      p.R125W (c.373C>T), p.G148R (c.442G>A), p.M173V (c.517A>G), p.T191M (c.572C>T),
      p.A226T (c.676G>A), p.C275Y (c.824G>A), p.R336C (c.1006C>T), p.R336H (c.1007G>A),
      p.L338P (c.1013T>C), p.S349N (c.1046G>A), p.R379Q (c.1136G>A), p.L456P
      (c.1367T>C), p.G522fsX540 (c.1566delG), and p.R548Q (c.1643G>A). Eleven of the
      mutant alleles exhibited an activity lower than 4% of the wild-type protein. In
      contrast, mutations p.A226T and p.M173V presented 20% and 40% of the wild-type
      activity, respectively, whereas the activity of p.R548Q was up to 60% of the wild
      type. This suggests that it is a new rare variant rather than a pathogenic
      mutation. Most of the mutated proteins exhibited a decreased signal in Western
      blot analyses. The non-denaturing PAGE revealed that the wild-type protein
      retained the capacity to form a multimeric quaternary structure, whereas in the
      mutations p.M173V, p.A226T, and p.G548Q, this structure grade was dramatically
      reduced and was completely absent in the rest of the mutations.

PMID- 16429403
TI  - BMPR2 gene rearrangements account for a significant proportion of mutations in
      familial and idiopathic pulmonary arterial hypertension.
AB  - Mutations of the BMPR2 gene predispose to pulmonary arterial hypertension (PAH),
      a serious, progressive disease of the pulmonary vascular system. However, despite
      the fact that most PAH families are consistent with linkage to the BMPR2 locus,
      sequencing only identifies mutations in some 55% of familial cases and between
      10% and 40% of cases without a family history (idiopathic or IPAH). We therefore
      conducted a systematic analysis for larger gene rearrangements in panels of both
      familial and idiopathic PAH cases that were negative on sequencing of coding
      regions. Analysis of exon dosage across the entire gene using Multiplex Ligation
      dependent Probe Amplification identified nine novel rearrangements and enabled
      full characterization at the exon level of previously reported deletions.
      Overall, BMPR2 rearrangements were identified in 7 of 58 families and 6 of 126
      IPAH cases, suggesting that gross rearrangements underlie around 12% of all FPAH
      cases and 5% of IPAH. Importantly, two deletions encompassed all functional
      protein domains and are predicted to result in null mutations, providing the
      strongest support yet that the predominant molecular mechanism for disease
      predisposition is haploinsufficiency. Dosage analysis should now be considered an
      integral of part of the molecular work-up of PAH patients.

PMID- 16429404
TI  - DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population.
AB  - Hereditary haemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome) is an
      autosomal dominant disorder characterized by localized angiodysplasia due to
      mutations in endoglin, ALK-1 gene, and a still unidentified locus. The lack of
      highly recurrent mutations, locus heterogeneity, and the presence of mutations in
      almost all coding exons of the two genes makes the screening for mutations time
      consuming and costly. In the present study, we developed a DHPLC-based protocol
      for mutation detection in ALK1 and ENG genes through retrospective analysis of
      known sequence variants, 20 causative mutations and 11 polymorphisms, and a
      prospective analysis on 47 probands with unknown mutation. Overall DHPLC analysis
      identified the causative mutation in 61 out 66 DNA samples (92.4%). We found 31
      different mutations in the ALK1 gene, of which 15 are novel, and 20, of which 12
      are novel, in the ENG gene, thus providing for the first time the mutational
      spectrum in a cohort of Italian HHT patients. In addition, we characterized the
      splicing pattern of ALK1 gene in lymphoblastoid cells, both in normal controls
      and in two individuals carrying a mutation in the non-invariant -3 position of
      the acceptor splice site upstream exon 6 (c.626-3C>G). Functional essay
      demonstrated the existence, also in normal individuals, of a small proportion of
      ALK1 alternative splicing, due to exon 5 skipping, and the presence of further
      aberrant splicing isoforms in the individuals carrying the c.626-3C>G mutation.

PMID- 16429405
TI  - Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of
      Infancy (HI).
AB  - Hyperinsulinism of Infancy (HI) is a clinical disorder characterized by
      deregulation of insulin secretion that leads to profound hypoglycemia. Mutations
      in genes encoding the ATP-regulated potassium channels of the pancreatic beta
      cell, namely ABCC8 (SUR1) and KCNJ11 (Kir6.2), are the major genetic known cause
      of the disease. To elucidate the genetic etiology of HI in the uncharacterized
      Spanish population, we conducted extensive sequencing analysis of the ABCC8
      (83.5Kb) and KCNJ11 (1.7Kb) genes in 34 Spanish HI patients. Mutations in ABCC8
      were detected for both alleles in 13 patients, while ten patients carried only
      one mutation in one of the ABCC8 alleles. We have detected 22 novel and seven
      previously described mutations in ABCC8, approximately 60% of them lead to a
      premature termination signal, which would result in truncated SUR1 proteins. No
      mutations were found in the KCNJ11 gene. In addition, we report for the first
      time a 3914bp macrodeletion associated with the HI disorder. The potential
      pathogenicity of several additional variants is discussed. The spatial pattern of
      three pathological mutations suggests possible geographical founder effects. This
      work reveals for first time the involvement of KATP channels in the pathogenesis
      of an important proportion (approximately 68%) of Spanish HI patients. The
      spectrum of mutations in Spanish HI patients provides an important tool for
      diagnosis and prognosis of HI patients in the Spanish population, as well as for
      genetic counseling of HI families.

PMID- 16429406
TI  - Novel inactivating mutations of FANCC in Brazilian patients with Fanconi anemia.
AB  - We have identified three novel FANCC mutations, a truncating single base
      insertion in exon 4 (c.455_456dupA), a point mutation in exon 13 (c.1390C>T), and
      a splice site mutation leading to deletion of exon 9, in two Brazilian FA-C
      patients, each a compound heterozygote. Using complementation analyses, we
      confirmed that two of these mutations inactivate the function of the FANCC
      protein.

PMID- 16429407
TI  - Novel PRG4 mutations underlie CACP in Saudi families.
AB  - The camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is an
      autosomal recessive disorder caused by mutations in the PRG4 (Proteoglycan 4)
      gene. Manifestations vary across families as well as between affected individuals
      from the same family, with camptodactyly and arthropathy of the knees the most
      ubiquitous, while pericarditis is evident in only one-fifth of all reported
      cases. Thus far only eight pathogenic mutations have been described in this gene.
      We examined seven newly diagnosed childhood patients of this syndrome, hailing
      from four unrelated families of Saudi origin. Five novel mutations were
      uncovered, including four frameshift deletions and one nonsense mutation
      (c.923_924delAA, c.3125_3128delGAGT, c.3139_3140delAA, c.3276_3277delAA,
      c.4078A>T). No genotype/phenotype association was observed. Because all mutations
      reported in CACP patients thus far predict premature truncation, we hypothesize
      that missense mutations are either not physiologically relevant, or that they
      trigger a clinical phenotype that is distinct from classical CACP. This is only
      the second published communication on PRG4 mutations, and increases the number of
      reported mutations for all ethnicities from 8 to 13, and for the Arab population
      specifically from one to six.

PMID- 16429409
TI  - Lethal double infection with Acremonium strictum and Aspergillus fumigatus during
      induction chemotherapy in a child with ALL.
AB  - Fungal infections are a major cause of morbidity and mortality in patients during
      chemotherapeutic treatments and malignant hematologic disease. We present a case
      of a double fungal infection with disseminated Acremonium strictum (A. strictum)
      and pulmonary Aspergillus fumigatus (A. fumigatus) and its rapid clinical course.
      A 17-year-old boy with prolonged neutropenia developed a disseminated fungal
      infection during induction chemotherapy of his acute lymphoblastic leukemia. The
      infection was rapidly lethal despite neutrophil recovery and early antifungal
      combination therapy with amphotericin B and caspofungin. Since there are only a
      few reports about invasive Acremonium infections, we present this case with
      regard to differences in the clinic pathologic features of Aspergillosis and
      other opportunistic fungal infections due to Fusarium or Acremonium species.

PMID- 16429408
TI  - Advances in proteomics data analysis and display using an accurate mass and time
      tag approach.
AB  - Proteomics has recently demonstrated utility for increasing the understanding of
      cellular processes on the molecular level as a component of systems biology
      approaches and for identifying potential biomarkers of various disease states.
      The large amount of data generated by utilizing high efficiency (e.g.,
      chromatographic) separations coupled with high mass accuracy mass spectrometry
      for high-throughput proteomics analyses presents challenges related to data
      processing, analysis, and display. This review focuses on recent advances in
      nanoLC-FTICR-MS-based proteomics approaches and the accompanying data processing
      tools that have been developed to display and interpret the large volumes of data
      being produced.

PMID- 16429410
TI  - Using pseudo amino acid composition to predict protein structural classes:
      approached with complexity measure factor.
AB  - The structural class is an important feature widely used to characterize the
      overall folding type of a protein. How to improve the prediction quality for
      protein structural classification by effectively incorporating the sequence-order
      effects is an important and challenging problem. Based on the concept of the
      pseudo amino acid composition [Chou, K. C. Proteins Struct Funct Genet 2001, 43,
      246; Erratum: Proteins Struct Funct Genet 2001, 44, 60], a novel approach for
      measuring the complexity of a protein sequence was introduced. The advantage by
      incorporating the complexity measure factor into the pseudo amino acid
      composition as one of its components is that it can catch the essence of the
      overall sequence pattern of a protein and hence more effectively reflect its
      sequence-order effects. It was demonstrated thru the jackknife crossvalidation
      test that the overall success rate by the new approach was significantly higher
      than those by the others. It has not escaped our notice that the introduction of
      the complexity measure factor can also be used to improve the prediction quality
      for, among many other protein attributes, subcellular localization, enzyme family
      class, membrane protein type, and G-protein couple receptor type.

PMID- 16429412
TI  - Surgical interventions for the treatment of radiation-induced alopecia in
      pediatric practice.
AB  - Permanent alopecia can occur following treatment for pediatric malignant disease,
      especially cranial irradiation, resulting in identity and self-image problems.
      This late effect is usually addressed through external cosmesis and psychological
      adjustment. Surgical options are less commonly utilized. The experience of
      reconstructive procedures in patients at RLC NHS Trust, Alder Hey with alopecia
      is presented. Four patients had scalp tissue expansion and one had hair
      transplantation. The reconstructive options available are discussed as well as
      the potential opportunities and difficulties in this population. Post
      radiotherapy alopecia can be successfully addressed by reconstructive surgery,
      and should be considered more often in this population.

PMID- 16429411
TI  - Randomized controlled trial of intraputamenal glial cell line-derived
      neurotrophic factor infusion in Parkinson disease.
AB  - OBJECTIVE: Glial cell line-derived neurotrophic factor (GDNF) exerts potent
      trophic influence on midbrain dopaminergic neurons. This randomized controlled
      clinical trial was designed to confirm initial clinical benefits observed in a
      small, open-label trial using intraputamenal (Ipu) infusion of recombinant human
      GDNF (liatermin). METHODS: Thirty-four PD patients were randomized 1 to 1 to
      receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or
      placebo. The primary end point was the change in Unified Parkinson Disease Rating
      Scale (UPDRS) motor score in the practically defined off condition at 6 months.
      Secondary end points included other UPDRS scores, motor tests, dyskinesia
      ratings, patient diaries, and (18)F-dopa uptake. RESULTS: At 6 months, mean
      percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the
      liatermin and placebo groups, respectively. This treatment difference was not
      significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end
      point results were similar between the groups. A 32.5% treatment difference
      favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed.
      Serious, device-related adverse events required surgical repositioning of
      catheters in two patients and removal of devices in another. Neutralizing
      antiliatermin antibodies were detected in three patients (one on-study and two in
      the open-label extension). INTERPRETATION: Liatermin did not confer the
      predetermined level of clinical benefit to patients with PD despite increased
      (18)F-dopa uptake. It is uncertain whether technical differences between this
      trial and positive open-label studies contributed in any way this negative
      outcome.

PMID- 16429413
TI  - Collection, storage, and infusion of stem cells in children with high-risk
      neuroblastoma: saving for a rainy day.
AB  - In this position statement issued by the Hematopoietic Stem Cell Transplant
      Discipline and the Neuroblastoma Disease Committee of the Children's Oncology
      Group (COG), we address the feasibility and advisability of collecting sufficient
      peripheral blood stem cells in neuroblastoma patients to both support the planned
      initial HDC/SCR procedure(s) as well as allow for therapies, potentially utilized
      after a recurrence of disease, that may require PBSC support. An additional
      aliquot of cells for potential subsequent therapies could be collected at the
      time of the initial PBSC apheresis episode, by any of extending the collection
      time, extending the apheresis episode by a single day, or cryopreserving a
      separate aliquot from collections in which large numbers of CD34+ cells are
      collected.

PMID- 16429414
TI  - Nutritional significance of the selective ingestion of Albizia zygia gum exudate
      by wild chimpanzees in Bossou, Guinea.
AB  - The selective ingestion of plant gum exudates by chimpanzees has been frequently
      observed at various study sites. At Bossou, Guinea, chimpanzees also frequently
      ingest Albizia zygia gum exudate. A functional explanation for this behavior is
      lacking, so we evaluated its possible contribution of energy in the form of short
      chain fatty acids (SCFA) as well as minerals. An in vitro fermentation study of
      A. zygia gum using the fecal bacteria of a Bossou chimpanzee showed that
      carboxylic acids were produced with a 6-hr lag phase up to 44 mmol/l by 18 hr of
      incubation. Acetate was the most abundant acid produced, followed by lactate and
      propionate. The energy supplied from the fermentation of a piece of gum exudate
      (20-30 g) was negligible in comparison with the estimated daily energy
      requirements of chimpanzees in the wild. However, A. zygia gum exudate (20-30 g)
      can supply sufficient amounts of calcium, manganese, magnesium, and potassium to
      fulfill the daily requirements for these minerals in chimpanzees.

PMID- 16429415
TI  - Lethal intergroup aggression by chimpanzees in Kibale National Park, Uganda.
AB  - Chimpanzees (Pan troglodytes) have hostile intergroup relations throughout most
      or all of their geographic range. Hostilities include aggressive encounters
      between members of neighboring communities during foraging and during patrols in
      which members of one community search for neighbors near territory boundaries.
      Attacks on neighbors involve coalitions of adult males, and are sometimes fatal.
      Targets include members of all age/sex classes, but the risk of lethal intergroup
      coalitionary aggression is highest for adult males and infants, and lowest for
      sexually swollen females. The best-supported adaptive explanation for such
      behavior is that fission-fusion sociality allows opportunities for low-cost
      attacks that, when successful, enhance the food supply for members of the
      attackers' community, improve survivorship, and increase female fertility. We add
      to the database on intergroup coalitionary aggression in chimpanzees by
      describing three fatal attacks on adult males, plus a fourth attack on an adult
      male and an attack on a juvenile that were almost certainly fatal. Observers saw
      four of these attacks and inferred the fifth from forensic and behavioral
      evidence. The attackers were males in two habituated, unprovisioned communities
      (Ngogo and Kanyawara) in Kibale National Park, Uganda. We also summarize data on
      other intercommunity attacks at Ngogo. Our observations are consistent with the
      "imbalance of power" hypothesis [Manson & Wrangham, Current Anthropology 32:369
      390, 1991] and support the argument that lethal coalitionary intergroup
      aggression by male chimpanzees is part of an evolved behavioral strategy.

PMID- 16429416
TI  - Describing the organization of dominance relationships by dominance-directed tree
      method.
AB  - Methods to describe dominance hierarchies are a key tool in primatology studies.
      Most current methods are appropriate for analyzing linear and near-linear
      hierarchies; however, more complex structures are common in primate groups. We
      propose a method termed "dominance-directed tree." This method is based on graph
      theory and set theory to analyze dominance relationships in social groups. The
      method constructs a transitive matrix by imposing transitivity to the dominance
      matrix and produces a graphical representation of the dominance relationships,
      which allows an easy visualization of the hierarchical position of the
      individuals, or subsets of individuals. The method is also able to detect partial
      and complete hierarchies, and to describe situations in which hierarchical and
      nonhierarchical principles operate. To illustrate the method, we apply a
      dominance tree analysis to artificial data and empirical data from a group of
      Cebus apella.

PMID- 16429417
TI  - Foraging ecology of howler monkeys in a cacao (Theobroma cacao) plantation in
      Comalcalco, Mexico.
AB  - Recent evidence indicates that primate populations may persist in neotropical
      fragmented landscapes by using arboreal agroecosystems, which may provide
      temporary habitats, increased areas of vegetation, and connectivity, among other
      benefits. However, limited data are available on how primates are able to sustain
      themselves in such manmade habitats. We report the results of a 9-month-long
      investigation of the feeding ecology of a troop of howler monkeys (n = 24) that
      have lived for the past 25 years in a 12-ha cacao plantation in the lowlands of
      Tabasco, Mexico. A vegetation census indicated the presence of 630 trees (> or
      =20 cm diameter at breast height (DBH)) of 32 shade species in the plantation.
      The howlers used 16 plant species (13 of which were trees) as sources of leaves,
      fruits, and flowers. Five shade tree species (Ficus cotinifolia, Pithecellobium
      saman, Gliricidia sepium, F. obtusifolia, and Ficus sp.) accounted for slightly
      over 80% of the total feeding time and 78% of the total number trees (n = 139)
      used by the howlers, and were consistently used by the howlers from month to
      month. The howlers spent an average of 51% of their monthly feeding time
      exploiting young leaves, 29% exploiting mature fruit, and 20% exploiting flowers
      and other plant items. Monthly consumption of young leaves varied from 23% to
      67%, and monthly consumption of ripe fruit varied from 12% to 64%. Differences in
      the protein-to-fiber ratio of young vs. mature leaves influenced diet selection
      by the monkeys. The howlers used 8.3 ha of the plantation area, and on average
      traveled 388 m per day in each month. The howlers preferred tree species whose
      contribution to the total tree biomass and density was above average for the
      shade-tree population in the plantation. Given the right conditions of management
      and protection, shaded arboreal plantations in fragmented landscapes can sustain
      segments of howler monkey populations for many decades.

PMID- 16429418
TI  - Labile sex differences in long calling in cotton-top tamarins.
AB  - Sex differences in behavior are quite common among nonhuman primates. In sexually
      monomorphic species, sex differences might be expected to be less evident than in
      polygynous and highly dimorphic species. Callitrichid primates (marmosets and
      tamarins) are cooperative breeders that exhibit little sexual size dimorphism.
      However, several sex differences in the structure and usage of vocalizations have
      been reported. In one such study, McConnell and Snowdon [Behaviour 97:273-296,
      1986] reported that female cotton-top tamarins (Saguinus oedipus) emitted
      significantly more normal long calls than males during simulated intergroup
      encounters. In the course of collecting a library of normal long calls, we
      replicated a portion of that study 20 years later with the same colony and
      similar methods. To our surprise we found a reversal of sex differences. In the
      same experimental situation, males gave significantly more normal long calls than
      females. In a further replication 2 years later, males still called more but the
      effect was less pronounced. The dramatic change in sex differences within the
      same species and colony over a 22-year period suggests that behavioral sex
      differences in callitrichids may be quite labile, and that repeated sampling over
      several years may be necessary to establish true sex differences.

PMID- 16429419
TI  - Pattern of maternal serum corticotropin-releasing hormone concentration during
      pregnancy in the common marmoset (Callithrix jacchus).
AB  - Corticotropin-releasing hormone (CRH), a potent neuropeptide, is produced by the
      placenta of anthropoid primates. No other mammals, including prosimian primates,
      are known to produce placental CRH. In humans, placental CRH appears to play an
      important role in the progression of pregnancy to parturition. Maternal
      circulating CRH begins to rise early in pregnancy and increases until
      parturition. Gorillas and chimpanzees share this pattern of increasing maternal
      CRH during pregnancy with humans. In humans, chimpanzees, and gorillas, maternal
      CRH and estradiol concentrations are correlated, consistent with the hypothesis
      that CRH is involved in the biosynthetic pathway for placental estrogen
      production. In contrast, in baboons, maternal circulating CRH rises precipitously
      early in pregnancy and then declines, though CRH is detectable until birth. This
      research was designed to investigate the pattern of maternal circulating CRH in
      the common marmoset during pregnancy. Blood samples were taken across gestation
      from nine subjects over 11 pregnancies, and the plasma was assayed for CRH. The
      pattern of maternal circulating CRH in the common marmoset was similar to that of
      the baboon, with a rapid rise starting at about 50 days postconception and a peak
      at approximately 70 days postconception. By 110 days postconception, CRH
      concentration had plateaued at a significantly lower value. The peak and mean
      values for CRH were associated with fetal number (e.g., females gestating
      triplets had higher values than females gestating twins). Urinary estradiol
      showed no association with plasma CRH concentration. Marmosets appear to differ
      from the great apes in this regard, and to share a pattern of maternal CRH during
      pregnancy with the baboon, indicating that the baboon and marmoset pattern may be
      ancestral. The function of the early rapid rise of CRH in baboons and marmosets,
      and the significance of this difference between monkeys and apes, are not known.

PMID- 16429420
TI  - Predation of arthropods by southern bearded sakis (Chiropotes satanas) in Eastern
      Brazilian Amazonia.
AB  - Bearded sakis are seed predators, but are also known to consume arthropods. This
      is the first detailed report of arthropod predation in southern bearded sakis
      (Chiropotes satanas). Two groups were monitored-one in continuous forest, and one
      on a small island-between January 2003 and February 2004. The arthropod prey
      included spiders and six insect orders. Island group members spent more time
      foraging for arthropods (3.8% vs. 2.6% of activity time) but ingested less prey
      (3.7% vs. 4.6% of feeding time). Arthropods accounted for a small proportion of
      feeding records in most months, but there were occasional sharp peaks due to the
      exploitation of temporary agglomerations of insects. In November, arthropods
      accounted for 26.6% and 14.2% of the feeding records of the mainland and island
      groups, respectively. The results suggest that bearded sakis actively seek
      arthropods as a dietary supplement, but that they represent a minor resource
      during most of the year, even under conditions of intense habitat fragmentation
      (island group).

PMID- 16429421
TI  - Habitat-specific ranging patterns of Dian's tarsiers (Tarsius dianae) as revealed
      by radiotracking.
AB  - Dian's tarsier Tarsius dianae, one of the smallest primates on earth, is endemic
      to the central regions of Sulawesi, Indonesia. To evaluate the effects of
      increasing land use by humans on the ranging patterns of this nocturnal insect
      hunter, four study plots along a gradient of anthropogenic disturbance were
      selected for this study. In these plots, 71 tarsiers were captured with mist
      nets, and 30 of these were fitted with 3.9 g radiotransmitters and subsequently
      tracked over the course of 2 weeks per animal. The average home ranges were 1.1
      1.8 ha in size, with the smallest ranges in slightly disturbed habitat and the
      largest ranges in a heavily disturbed plantation. These findings coincide with
      different estimates of insect abundance in the study plots. Nightly travel
      distances were smallest in undisturbed old-growth forest and slightly increased
      along a gradient of human disturbance. The tarsiers were most active shortly
      after dusk and just before dawn. The results of this comprehensive radiotracking
      study on tarsiers show that T. dianae adapts its ranging behavior to the degree
      and type of human land use. Integrated data on home range size and travel
      distance indicate that slightly disturbed forest is as favorable to these animals
      as undisturbed habitat. However, with increasing anthropogenic effects, the
      living conditions of the tarsiers appear to deteriorate, resulting in the
      necessity for larger home and night ranges. The results of this study provide an
      important tool for directing conservation efforts targeted at the survival of
      this primate in central Sulawesi.

PMID- 16429422
TI  - Evolution of high-performance swimming in sharks: transformations of the
      musculotendinous system from subcarangiform to thunniform swimmers.
AB  - In contrast to all other sharks, lamnid sharks perform a specialized fast and
      continuous "thunniform" type of locomotion, more similar to that of tunas than to
      any other known shark or bony fish. Within sharks, it has evolved from a
      subcarangiform mode. Experimental data show that the two swimming modes in sharks
      differ remarkably in kinematic patterns as well as in muscle activation patterns,
      but the morphology of the underlying musculotendinous system (red muscles and
      myosepta) that drives continuous locomotion remains largely unknown. The goal of
      this study was to identify differences in the musculotendinous system of the two
      swimming types and to evaluate these differences in an evolutionary context.
      Three subcarangiform sharks (the velvet belly lantern shark, Etmopterus spinax,
      the smallspotted catshark, Scyliorhinus canicula, and the blackmouth catshark,
      Galeus melanostomus) from the two major clades (two galeans, one squalean) and
      one lamnid shark, the shortfin mako, Isurus oxyrhinchus, were compared with
      respect to 1) the 3D shape of myomeres and myosepta of different body positions;
      2) the tendinous architecture (collagenous fiber pathways) of myosepta from
      different body positions; and 3) the association of red muscles with myoseptal
      tendons. Results show that the three subcarangiform sharks are morphologically
      similar but differ remarkably from the lamnid condition. Moreover, the
      "subcarangiform" morphology is similar to the condition known from teleostomes.
      Thus, major features of the "subcarangiform" condition in sharks have evolved
      early in gnathostome history: Myosepta have one main anterior-pointing cone and
      two posterior-pointing cones that project into the musculature. Within a single
      myoseptum cones are connected by longitudinally oriented tendons (the hypaxial
      and epaxial lateral and myorhabdoid tendons). Mediolaterally oriented tendons
      (epineural and epipleural tendons; mediolateral fibers) connect vertebral axis
      and skin. An individual lateral tendon spans only a short distance along the body
      (a fraction between 0.05 and 0.075 of total length, L, of the shark). This span
      is similar in all tendons along the body. Red muscles insert into the midregion
      of the lateral tendons. The shortfin mako differs substantially from this
      condition in several respects: Red muscles are internalized and separated from
      white muscles by a sheath of lubricative connective tissue. They insert into the
      anterior part of the hypaxial lateral tendon. Rostrocaudally, this tendon becomes
      very distinct and its span increases threefold (0.06L anteriorly to 0.19L
      posteriorly). Mediolateral fibers do not form distinct epineural/epipleural
      tendons in the mako. Since our morphological findings are in good accordance with
      experimental data it seems likely that the thunniform swimming mode has evolved
      along with the described morphological specializations.

PMID- 16429423
TI  - Dynamic contrast-enhanced MRI to quantify VEGF-enhanced tissue-engineered bladder
      graft neovascularization: pilot study.
AB  - Tissue engineered organs require an immediately perfused vascular tree.
      Currently, neovascularization assessment requires animal sacrifice and graft
      harvest. In this pilot study we assess whether neovascularization of an
      engineered urinary bladder construct is enhanced with vascular-derived
      endothelial growth factor (VEGF) and assessable non-invasively with dynamic
      contrast-enhanced MRI (DCE-MRI). Rabbit bladder acellular matrix was hybridized
      with hyaluronic acid (ACM-HA), fortified with one of three concentrations (0 ng,
      10 ng, or 20 ng per gram of tissue) of vascular-derived endothelial growth factor
      (VEGF), and grafted onto bladders in nine rabbits (3 per VEGF concentration). At
      1, 2 and 3 weeks, one rabbit from each VEGF group underwent DCE-MRI and graft
      harvest. Microvasculature was quantified with scrial optical transverse
      sectioning of CD31 stained whole mounts using PCl software. Masson trichrome and
      H&E staining were used to assess cellular proliferation and fibrosis. There was a
      significant difference in mean microvascular area (MVA) between the 10 and 20 ng
      VEGF groups (230187 vs 477894 microm2, P=0.014) but not between the 0 and 10 ng
      groups (210497 microm2, P=0.21). Gadolinium uptake increased with MVA and
      correlated with it on linear regression analysis (Pearson's correlation
      coefficient r=0.71). At three weeks, stromal cellularity was greatest, and
      fibrosis was least, in the high VEGF group. This preliminary work demonstrates
      improved neovascularization of bladder constructs with VEGF fortification of ACM
      HA and the feasibility of MRI as a non-invasive method to assume angiogenesis in
      tissue engineered constructs.

PMID- 16429424
TI  - Association of common haplotypes of surfactant protein A1 and A2 (SFTPA1 and
      SFTPA2) genes with severity of lung disease in cystic fibrosis.
AB  - Most individual cystic fibrosis transmembrane conductance regulator (CFTR)
      mutations appear not to correlate directly with severity of lung damage in cystic
      fibrosis (CF). Components of innate immunity, namely, mannose-binding lectin
      (MBL2), and surfactant protein A1 and A2 genes (SFTPA1 and SFTPA2), were shown to
      be critical in pulmonary host defenses. A pilot association study was conducted
      to identify genetic modifiers of lung disease in adult patients with CF. The
      structural and promoter (-221x/y) variants of MBL2, variants at codons 19, 50,
      62, and 219 of SFTPA1, and at codons 9, 91, and 223 for SFTPA2, were studied in
      135 adults with CF and compared to their forced expired volume in 1 sec (FEV1),
      diffusion of CO (DLCO), and other pulmonary scores. Predicted FEV1 was
      significantly lower in adults with the SFTPA1 6A3 allele and SFTPA2 1A1) allele
      (P = 0.01 and 0.009, respectively). The extended haplotype 6A3/1A1, which
      includes SFTPA1 and SFTPA2, was associated with lower pulmonary function, using
      FEV1 (P = 0.005) and poor pulmonary scores which were determined by American
      Medical Association, American Thoracic Society, and modified Shwachman-Kulczycki
      scores. Lower FEV1 and DLCO values were associated with MBL2 coding variants in
      those who had the DeltaF508 CFTR mutation (P = 0.03 and 0.004, respectively).
      These results support the current hypothesis that variants in pulmonary host
      defense molecules are potentially genetic modifiers of pulmonary disease in CF.
      Further work in larger populations is required to provide important new insights
      into the pathogenesis of CF.

PMID- 16429426
TI  - Epstein-Barr virus-associated bronchial leiomyoma in a boy with cellular
      immunodeficiency.
AB  - Bronchial leiomyoma is a rare disease in children. Recently, the association of
      leiomyoma and HIV infection was reported. We describe a boy with a cellular
      immunodeficiency, who had endobronchial leiomyoma. The tumor cells were positive
      for Epstein-Barr virus-encoded RNA-1 (EBER-1) and Epstein-Barr virus-determined
      nuclear antigen-2, suggesting a role of Epstein-Barr virus in the pathogenesis of
      leiomyoma.

PMID- 16429425
TI  - Cystic fibrosis mutations with widely variable phenotype: the D1152H example.
AB  - D1152H is a type IV cystic fibrosis transmembrane regulator (CFTR) mutation
      associated with abnormal chloride gating. Although comprising 5-6% of mutations
      on genetic screening, clinical reports of cystic fibrosis (CF) are rare,
      suggesting that the disease is mild, atypical, or even absent. We describe our
      experience, which contrasts with this assumption, in a retrospective case series
      encompassing 91 CF patients (74 Jewish) aged 8 months to 56 years, from 2000
      2005. Nine patients of varied Jewish ethnic origins were homozygous (2 patients)
      or compound heterozygous for D1152H with 11 of 182 potential alleles (6%). Five
      were diagnosed at age 33-49 years. Of 4 infants, 1 was diagnosed by prenatal
      screening, 1 had a prenatal dilated bowel, and 1 had pulmonary symptoms. Sweat
      chloride was 28-120 meq/l. Three adults had chronic mucoid Pseudomonas aeruginosa
      in sputum, and a forced expired volume in 1 sec (FEV1) of 20-55%. One was on
      bilevel positive airway pressure (BIPAP) ventilation. The infants had pulmonary
      symptoms that responded well to therapy. All 9 patients had good nutrition, 6
      were pancreatic-sufficient, and 3 adults had subclinical pancreatic
      insufficiency. Three adults had recurrent pancreatitis. None had a bowel
      obstruction. Two of 3 adult males were fertile. Although asymptomatic at times,
      the D1152H mutation is associated with a broad clinical spectrum. This
      information is crucial for genetic counseling. Lung disease may be evident from
      infancy, and is severe in some adults, although all have outlived the median life
      expectancy of CF. Hopefully, with early diagnosis and therapy, prognosis can be
      good. A multicenter study of this mutation is warranted.

PMID- 16429427
TI  - Montelukast administered in the morning or evening to prevent exercise-induced
      bronchoconstriction in children.
AB  - Montelukast is recommended to be taken in the evening. The effectiveness of this
      drug to prevent exercise-induced bronchoconstriction (EIB) in children was
      already evaluated. However, there is no information to determine if this
      effectiveness could vary depending on dosage time. Children (n = 24) with a
      documented history of EIB performed an exercise challenge test before starting
      montelukast treatment. Twelve children were randomly allocated to receive the
      drug in the morning for 2 weeks, and another 12 to receive it in the evening.
      After this treatment period and after a week of washout, the children were
      crossed over. An exercise test was repeated after the first and second periods of
      treatment. Values obtained after morning or evening dosage were compared with
      pretreatment values for the whole group of children. There was a significant
      effect of montelukast for protecting against EIB, measured both as percent of
      maximum fall in forced expired volume in 1 sec (FEV1) (18.9 +/- 9.7, morning,
      18.7 +/- 11.3, evening, vs. 27.5 +/- 9.8, pretreatment; P < 0.05) or as area
      under the curve (156.4 +/- 102.0, morning, 145.4 +/- 130.6, evening, vs. 294.3 +/
      156.5, pretreatment; P < 0.005). There were no statistical differences between
      taking the drug in the morning or evening. In conclusion, montelukast, taken for
      2 weeks, is equally effective in exercise-induced bronchoconstriction when dosing
      either in the morning or in the evening.

PMID- 16429428
TI  - Is there a relationship between ELF free-IGF-1 levels and fibrotic process
      enhancement characterizing CLD development in neutropenic premature babies?

PMID- 16429431
TI  - DRD4 gene variant associated with body mass: the National Longitudinal Study of
      Adolescent Health.
AB  - In this article we report a novel statistically significant association between
      the D4.7/D4.7 genotype of the DRD4 gene and the body mass of black and Hispanic
      participants in the National Longitudinal Study of Adolescent Health (Add
      Health). We investigated the role of the 48-bp repeat polymorphism of the
      dopamine receptor 4 gene (DRD4) in body mass regulation in 2,277 adolescents and
      young adults followed in 1995 (12-18 years old), 1996, and 2002 by Add Health.
      After the effects of age, sex, and ethnicity were adjusted, the D4.7/D4.7
      genotype reduced the body mass index (BMI)-percentile score by 15 and 12.5, as
      compared to those with other genotypes, for African-Americans (P = 0.0047) and
      Hispanic-Americans (P = 0.037), respectively. Although the D4.7/D4.7 genotype was
      associated with a lower BMI-percentile score in white individuals compared to
      other genotypes, the difference was not significant. Individuals heterozygous for
      D4.7 did not differ from those with the other/other genotype.

PMID- 16429430
TI  - Effect of low altitude at the Dead Sea on exercise capacity and cardiopulmonary
      response to exercise in cystic fibrosis patients with moderate to severe lung
      disease.
AB  - Oxygen supplementation may improve exercise tolerance and the physiological
      response to exercise in cystic fibrosis (CF) patients. Elevated barometric
      pressure at low altitude is a simple means of increasing the quantity of inspired
      oxygen. Our objectives were to examine the effect of natural oxygen enrichment
      (at the Dead Sea, 396 m below sea level) on exercise capacity, and the
      physiological responses to maximal and submaximal exercise in CF patients.
      Patients were tested twice: at sea level (barometric pressure, 754 +/- 6 mmHg,
      mean +/- SD), and at the Dead Sea (barometric pressure, 791 +/- 3 mmHg), in a
      randomized crossover design. We studied 14 CF patients (6 females, 8 males), aged
      15-45 years, with moderate to severe lung disease (mean forced expired volume in
      1 sec = 50.0 +/- 11.2% predicted). Tests at each site included resting
      spirometry, anthropometry, a graded submaximal exercise test, a maximal exercise
      test on a treadmill, and a 6-min walk test. Tests were performed in identical
      order at both sites. Tests at the Dead Sea were performed 72 hr after arrival. No
      differences between sites were observed in lung function at rest. Peak oxygen
      consumption was significantly improved at the Dead Sea compared with sea level
      (1.68 +/- 0.73 vs. 1.57 +/- 0.74 l/min, respectively, P = 0.05), along with an
      improvement in the ventilatory equivalent for oxygen (41.2 +/- 6.3 vs. 46.1 +/-
      7.1, respectively, P < 0.05). During submaximal exercise, blood oxygen saturation
      improved at the Dead Sea compared with sea level at all exercise intensities (P <
      0.05). In conclusion, these results suggest that even a brief stay at the Dead
      Sea area may have physiological benefits for CF patients with moderate to severe
      lung disease.

PMID- 16429432
TI  - Singapore Human Mutation/Polymorphism Database: a country-specific database for
      mutations and polymorphisms in inherited disorders and candidate gene association
      studies.
AB  - There is a need for country/population-specific databases because the existence
      of population-specific mutations for single gene disorders is well documented,
      and there is also good evidence for ethnic differences in the frequencies of
      genetic variations involved in complex disorders. Thus the Singapore Human
      Mutation/Polymorphism Database (SHMPD) was created to provide clinicians and
      scientists access to a central genetic database for the Singapore population. The
      data catalogued in the database include mutations identified in Singapore for
      Mendelian diseases, and frequencies of polymorphisms that have been investigated
      in either healthy controls or samples associated with specific phenotypes. Data
      from journal articles identified by searches in PubMed and other online
      resources, and via personal communications with researchers were compiled and
      assembled into a single database. Genes are categorized alphabetically and are
      also searchable by name and disease. The information provided for each variant of
      the gene includes the protein encoded, phenotype association, gender, size, and
      ethnic origin of the sample, as well as the reported genotype and allele
      frequencies, and direct links to the corresponding abstracts on PubMed. Our
      database will facilitate molecular diagnosis of Mendelian disorders and improve
      study designs for complex traits. It will be useful not only for researchers in
      Singapore, but also for those in countries with similar ethnic backgrounds, such
      as China, Taiwan, Hong Kong, Indonesia, and Malaysia.

PMID- 16429433
TI  - Alcohol use in congenital central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome (CCHS) is a rare disorder where there
      is failure of automatic control of breathing. With improved recognition of CCHS,
      more children are appropriately diagnosed and treated in infancy, allowing
      survival into adult years. Because most of these children are able to participate
      in regular school, they are exposed to common adolescent behaviors, such as
      abusing alcohol and drugs. Alcohol and many illicit substances are known
      respiratory depressants. We report on 3 cases of adolescents/young adults with
      CCHS who had severe adverse events related to alcohol, including coma and death.
      This series illustrates the dangers of alcohol abuse in CCHS. We speculate that
      adolescents with CCHS may be less able to perceive the risks of substance abuse
      and impulsive behavior, leading to increased morbidity and mortality. Patients
      with CCHS appear to lack anxiety and the awareness that their inability to
      perceive physiologically dangerous levels of hypercarbia and hypoxia deprives
      them of important protective mechanisms.

PMID- 16429434
TI  - Applicability of interrupter resistance measurements for evaluation of exercise
      induced bronchoconstriction in children.
AB  - The interrupter technique is a noninvasive method for measuring air-flow
      resistance during tidal breathing. This method requires minimal cooperation, and
      is therefore promising for use in uncooperative children. The aim of this study
      was to evaluate applicability interrupter resistance (Rint) measurements in the
      assessment of exercise-induced bronchoconstriction (EIB). Fifty children aged 5
      12 years with mild to moderate asthma were tested by exercise challenge,
      consisting of free outdoor running for 6 min at 80-90% of maximal predicted heart
      rate for age. Rint, forced expiratory volume in 1 sec (FEV1), and peak expiratory
      flow (PEF) were measured before and 10 min after exercise. EIB was defined as a
      fall of 10% or more in FEV1 after exercise. The repeatability of Rint was
      assessed, and its response to exercise challenge was compared with current
      standardized methods. The mean intermeasurement coefficient of variation was 4.6%
      (SD, +/- 3.0%), and the repeatability coefficient was 0.056 kPa/l/sec. Eighteen
      (36%) of the 50 children had EIB after exercise challenge test. The area under
      the receiver-operating characteristic (ROC) curve was 0.953 (95% confidence
      interval, 0.853-0.992; P < 0.001), and the optimal Rint cutoff value was 15.2%,
      producing a sensitivity of 88.9% and a specificity of 96.9%. The positive and
      negative predictive values were 94.1% and 93.9%, respectively. The kappa value
      between FEV1 and Rint was 0.83. The repeatability of Rint measurements was good,
      and the results of exercise challenge tests using Rint measurements have
      excellent agreement with the current standardized methods to detect EIB.
      Considering that only minimal comprehension and coordination are needed without
      forced breathing technique, the Rint measurement can provide a useful alternative
      for assessment of EIB in children unable to perform reliable spirometry.

PMID- 16429436
TI  - Polysomnographic findings in 320 infants evaluated for apneic events.
AB  - Apnea is a common problem that causes significant parental anxiety. The aim of
      this study was to describe polysomnographic findings in infants who were referred
      over a 4-year period for an apnea and/or cyanotic event. Our hypothesis was that
      most infants with apnea or cyanosis events will have normal polysomnography
      (PSG). In total, 320 patients younger than 2 years old were recruited
      sequentially and prospectively. Patients underwent a day or overnight PSG by
      computerized polysomnograph; 78% of studies were performed with pH probe in situ.
      Subjects' ages ranged from 10 days to 21 months (55% male and 84% full-term
      babies); 55% and 74% were younger than 3 and 6 months, respectively. The average
      total sleep time was 473.4 min (SD, 52.3), with mean sleep efficiency of 83.5%.
      The distribution of sleep stages was 56.5% active, 38.5%, quiet and 5.1%
      indeterminate sleep. Sixty-nine percent (n = 220) of PSG studies were done
      overnight. There were significant differences in average sleep efficiency (78.1%
      vs. 83.3%) and REM sleep time (63.6% vs. 59.1%) between PSGs done during the day
      and overnight (P < 0.05). In total, 34 patients with apneas were studied. The
      median apnea index for the whole study population was 1.01 (range, 0.1-9.1). In
      conclusion, our study showed a high prevalence of normal polysomnographic
      findings in infants referred because of apnea and/or cyanotic events. New
      clinical prospective studies should be conducted to evaluate whether there is a
      correlation between PSG findings and outcome at follow-up of infants with a
      history of apnea and cyanosis.

PMID- 16429435
TI  - Pulmonary sarcoidosis in a 14-year-old boy diagnosed by low-dose CT-guided
      transthoracic lung biopsy.
AB  - Pulmonary sarcoidosis is a rare disease in the pediatric age group, characterized
      by the presence of epitheloid-cell granulomas. In stage 3 sarcoidosis, pulmonary
      infiltrates without hilar lymphadenopathy occur. Definitive diagnosis requires a
      histopathological specimen, which might be difficult to obtain by transbronchial
      biopsy. Multidetector computed tomography (MDCT)-guided transthoracic lung biopsy
      (TLB) is a well-established procedure in adults, but has only rarely been applied
      in children.A 14-year-old boy was admitted to hospital for evaluation of a
      chronic systemic disease with severe pulmonary manifestation. All investigations,
      including bronchosopy and bronchoalveolar lavage with microbiological and
      virological testing, had been negative. MDCT-guided TLB was performed on a 16
      section scanner with a low-dose protocol (single slices, 120 kV, 20 mAs), using a
      16-gauge biopsy device. The total effective dose was 0.4 mSv for the biopsy
      procedure. Histopathological examination revealed multiple epitheloid-cell
      granulomas with giant cells in the absence of microbiological or virological
      abnormalities. A diagnosis of stage 3 pulmonary sarcoidosis was made and systemic
      anti-inflammatory therapy was administered, which led to complete remission
      within weeks. MDCT-guided TLB can be a valuable instrument in assessing pulmonary
      manifestations of pediatric sarcoidosis, enabling precise histopathological
      diagnosis and adequate therapy. The use of low-dose protocols can substantially
      reduce radiation exposure without relevant loss of image information. MDCT-guided
      lung biopsy should be considered prior to open-lung surgery in selected patients
      with unclear pulmonary disease.

PMID- 16429437
TI  - Pasteurella multocida lung and liver abscess in an immune-competent child.
AB  - We report on a 20-month-old infant with a complicated lung and liver abscess
      caused by Pasteurella multocida after the child had been in close contact with a
      domestic cat. Surgical drainage confirmed lung and liver abscesses connected to
      each other, with involvement of the diaphragm.

PMID- 16429440
TI  - Morphology of the lower jaw and suspensorium in the Texas blindsnake,
      Leptotyphlops dulcis (Scolecophidia: Leptotyphlopidae).
AB  - Slender blindsnakes (Leptotyphlopidae) are known to use a unique feeding
      mechanism that involves rapid flexions of the tooth-bearing lower jaw. However,
      the morphology of the leptotyphlopid jaw apparatus has remained poorly studied
      due to the extremely small size of these snakes. Here I present a detailed
      description of the bones, cartilages, and ligaments of the lower jaw and
      suspensorium in a representative leptotyphlopid, Leptotyphlops dulcis, based on
      microanatomical studies of nearly 30 specimens prepared and examined in a variety
      of ways. The leptotyphlopid mandible is found to exhibit a complex mixture of
      symplesiomorphies shared with nonophidian squamates ("lizards"), synapomorphies
      shared with other snakes, and autapomorphies unique to Leptotyphlopidae. Most
      autapomorphies are functional correlates of the mandibular raking mechanism used
      by Leptotyphlops, primarily involving specializations of the intramandibular
      joint and the linkage between the suspensorium and the skull. Most notably, the
      quadrates are suspended via sliding articulations with the stapedes and do not
      articulate directly with the braincase. Posterior translation of the suspensorium
      at this loose, sliding articulation during jaw retraction may account for
      approximately one-third of the distance that prey are transported during each
      cycle of jaw flexion. This primary quadratostapedial articulation is believed to
      be unique among gnathostomes. Several anatomical features of the jaw apparatus
      suggest that Leptotyphlops evolved from more typical snake-like ancestors that:
      1) had already lost the firm symphysis between the distal tips of the mandibular
      rami; and 2) had already evolved a high degree of upper jaw mobility.

PMID- 16429441
TI  - From conical to spatulate: intra- and interspecific changes in tooth shape in
      closely related cichlids (Teleostei; Cichlidae: Eretmodini).
AB  - The Eretmodini are closely related cichlids endemic to Lake Tanganyika with very
      divergent oral tooth shapes, ranging from spatulate in Eretmodus to conical in
      Tanganicodus. To study how closely related cichlids can generate such divergent
      tooth shapes, we investigated how the enamel organ directs the development of
      spatulate teeth in Eretmodus cf. cyanostictus (lineage A), both in ontogeny and
      in adults, and of conical teeth in adult Tanganicodus cf. irsacae, using 3D
      reconstructions from serially sectioned tooth germs. The spatulate oral tooth
      shape that characterizes adult E. cf. cyanostictus (lineage A) is preceded early
      in ontogeny by a conical tooth shape. We propose two possible hypotheses to
      account for changes in the folding of the enamel organ (in particular its
      epithelio-mesenchymal boundary) capable of generating such distinct tooth shapes.
      Different arguments lead us to favor the hypothesis of an asymmetric growth and
      differentiation of the enamel organ, such that the tip of a conical tooth
      corresponds to one "corner" of a spatulate tooth. Applying current molecular
      models of tooth shape variation, this would imply the existence of asymmetric
      fields of inhibition. Whether such asymmetric growth reflects the reutilization
      of a simple mechanism operating in ontogeny has to be clarified.

PMID- 16429442
TI  - Confocal microscopy of the light organ crypts in juvenile Euprymna scolopes
      reveals their morphological complexity and dynamic function in symbiosis.
AB  - In the hours to days following hatching, the Hawaiian bobtail squid, Euprymna
      scolopes, obtains its light-emitting symbiont, Vibrio fischeri, from the
      surrounding environment and propagates the bacteria in the epithelial crypts of a
      specialized light organ. Three-dimensional analyses using confocal microscopy
      revealed that each of the three crypts on either side of the juvenile light organ
      is composed of four morphological regions. Progressing from the lateral pore to
      the medial blind end of each crypt, the regions consist of 1) a duct, 2) an
      antechamber, 3) a bottleneck, and 4) a deep region. Only the deep region houses a
      persistent bacterial population, whereas the duct, antechamber, and bottleneck
      serve as conduits through which the bacteria enter during initial colonization
      and exit during diel venting, a behavior in which approximately 90% of the
      symbionts are expelled each dawn. Our data suggest that, like the duct, the
      antechamber and bottleneck may function to promote and maintain the specificity
      of the symbiosis. Pronounced structural and functional differences among the deep
      regions of the three crypts, along with previously reported characterizations of
      embryogenesis, suggest a continued developmental progression in the first few
      days after hatching. Taken together, the results of this study reveal a high
      degree of complexity in the morphology of the crypts, as well as in the extent to
      which the three crypts and their constituent regions differ in function during
      the early stages of the symbiosis.

PMID- 16429444
TI  - Lipopolysaccharide-induced microglial activation induces learning and memory
      deficits without neuronal cell death in rats.
AB  - We used lipopolysaccharide (LPS) to activate microglia that play an important
      role in the brain immune system. LPS injected into the rat hippocampus CA1 region
      activated microglial cells resulting in an increased production of interleukin
      (IL)-1beta and tumor necrosis factor (TNF)-alpha in the hippocampus during the
      initial stage of treatment. Immunostaining for IL-1beta was increased at 6 hr
      after LPS injection. IL-1beta-immunopositive cells were co-localized with
      immunostaining for CD11b. Subacute treatment with LPS by the same route for 5
      days caused long-term activation of microglia and induced learning and memory
      deficits in animals when examined with a step-through passive avoidance test, but
      histochemical analysis showed that neuronal cell death was not observed under
      these experimental conditions. The increased expression of the heme oxygenase-1
      (HO-1) gene, an oxidative stress maker, was observed. However, the genetic
      expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB,
      decreased during the course of LPS treatment. We found decreases in [3H]MK801
      binding in the hippocampus CA1 region by LPS-treatment for 5 days. The data shows
      that glutamatergic transmission was attenuated in the LPS-treated rats. These
      results suggest that long-term activation of microglia induced by LPS results in
      a decrease of glutamatergic transmission that leads to learning and memory
      deficits without neuronal cell death. The physiologic significance of these
      findings is discussed.

PMID- 16429445
TI  - Desmoplastic small round cell tumor of the pleura.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare neoplasm with aggressive
      behavior. Usually it presents as a peritoneal mass, although other cases in
      various locations have been described. Since less than 10 cases of primary DSRCT
      in the pleura have been described, it is of interest to report a pediatric case
      arising from the pleura. The diagnosis was confirmed by molecular detection of
      the EWS/WT-1 fusion gene product. Multidisciplinary treatment with chemotherapy,
      radiotherapy, and surgical resection resulted in a progression-free survival time
      above the median survival, suggesting that this conventional approach could prove
      effective for this rare and very aggressive malignancy.

PMID- 16429446
TI  - HPSE-1 expression and functionality in differentiating neural cells.
AB  - The study of cellular differentiation encompasses many vital parts of biology and
      medicine. Heparan sulfate proteoglycans (HSPG) are essential and ubiquitous
      macromolecules associated with the cell surface and extracellular matrix (ECM) of
      a wide range of cells and tissues. Heparan sulfate chains (HS) of HSPG bind and
      sequester a multitude of extracellular ligands, including growth factors,
      cytokines, chemokines, enzymes, and lipoproteins. Enzymatic degradation of HS is
      therefore involved in processes such as cell proliferation, migration, and
      differentiation. Heparanase (HPSE-1) is an HS degradative enzyme associated with
      inflammation and lipid metabolism and is a critical molecular determinant in
      cancer metastasis. The enzyme acts as an endo-beta-D-glucuronidase, which
      degrades HS at specific intrachain sites, resulting in HS fragments of discrete
      molecular weights that retain biological function. HPSE-1's relevance as the only
      example of cloned/purified mammalian HS degradative enzyme led us to investigate
      its functionality in human olfactory epithelium (HOE) cells as a paradigm for
      HPSE-1's roles in neural cell differentiation. We provide the first evidence of
      1) HPSE-1 presence in HOE cells and 2) a highly significant increase of HPSE-1
      mRNA and enzyme activity in differentiating vs. proliferating HOE cells. Our data
      suggest that an augmented HPSE-1 activity may represent a physiological mechanism
      involved in neural cellular differentiation.

PMID- 16429447
TI  - Corticosteroids delay remyelination of experimental demyelination in the rodent
      central nervous system.
AB  - High dose corticosteroid (CS) administration is a common mode of therapy in
      treatment of acute relapses in multiple sclerosis (MS) but the effects of CS on
      remyelination and the cellular mechanisms mediating this repair process are
      controversial. We have examined CS effects on repair of toxin-induced
      demyelinating lesions in the adult rat spinal cord. Corticosteroids reduced the
      extent of oligodendrocyte remyelination at 1 month post lesion (whereas Schwann
      cell mediated repair was unaffected). However, CS did not cause permanent
      impairment of remyelination as lesions were fully remyelinated at 2 months after
      cessation of treatment. The delay in oligodendrocyte mediated repair could be
      attributed to inhibition of differentiation of oligodendrocyte progenitor cells
      (OPCs) into oligodendrocytes, with no effect of CS treatment observed on OPC
      colonisation of the lesions. No differences were observed in animals treated with
      methylprednisolone succinate alone or with a subsequent prednisone taper
      indicating that CS effects occur at an early stage of repair. The potential
      consequences of delayed remyelination in inflammatory lesions are discussed.

PMID- 16429448
TI  - Proinflammatory cytokines expression in noise-induced damaged cochlea.
AB  - Recent studies have showed that inflammatory responses occur in inner ear under
      various damaging conditions including noise-overstimulation. We evaluated the
      time-dependent expression of proinflammatory cytokines in noise-exposed rat
      cochlea. Among several detected cytokines, real-time RT-PCR showed that
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were significantly induced
      3 hr after noise exposure, and quickly downregulated to the basal level. Tumor
      necrosis factor-alpha (TNF-alpha) was also slightly upregulated immediately after
      noise exposure. Immunohistochemical analysis showed that IL-6 expression was
      distinctively induced within the lateral side of the spiral ligament. Sequential
      expression analysis showed that IL-6 immunoreactivity was initially found in the
      cytoplasm of lateral wall cells, including Type IV and III fibrocytes, and
      expanded broader throughout the lateral wall, finally to the stria vascularis.
      Because of the negative Iba-1 staining, IL-6 expression in the early-phase was
      not due to macrophage or microglia activation. IL-6 was also detected in spiral
      ganglion neurons at 12 and 24 hr after noise exposure. Our data demonstrates the
      production of proinflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6,
      in early phase of noise overstimulated cochlea. IL-6 expression was observed in
      the spiral ligament, stria vascularis, and spiral ganglion neurons. These
      cytokines, produced by the cochlear structure itself in response to noise
      exposure, may initiate an inflammatory response and have some role in the
      mechanism of noise-induced cochlear damage.

PMID- 16429449
TI  - Algorithm for difficult distal protection system retrieval in carotid stenting.

PMID- 16429453
TI  - Asymmetric organocatalytic Henry reaction.

PMID- 16429450
TI  - Developing epidemic of melanoma in the Hispanic population of California.
AB  - BACKGROUND: Hispanics comprise almost one-third of the population of California,
      are the most rapidly increasing racial/ethnic group in the state, and represent
      almost one-third of all Hispanics in the U.S. California has among the highest
      rates of melanoma in the world, yet little is known about trends in melanoma in
      its Hispanic population. METHODS: Trends in invasive and in situ melanoma
      incidence data and melanoma mortality data, between 1988 and 2001, from the
      California Cancer Registry were analyzed. Trends in the Hispanic population were
      compared with those in the non-Hispanic white population. Time trends in tumors
      of differing thicknesses and histology were assessed. RESULTS: There was a
      statistically significant 1.8% per year increase in incidence of invasive
      melanomas among Hispanic males and a similar but non-statistically significant
      increase in invasive melanoma among Hispanic females between 1988 and 2001. Among
      Hispanic males and females tumors thicker than 1.5 mm at presentation increased
      at 11.6% per year (95% confidence interval [CI], 8.1, 15.2) and 8.9% per year
      (95% CI, 4.7, 13.3), respectively. CONCLUSION: Rates of invasive melanoma have
      increased markedly among Hispanics in California since 1988. In contrast to
      trends in the non-Hispanic white population, increases in melanoma in Hispanics
      have been confined to thicker tumors, whose prognosis is poor. We recommend that
      efforts be undertaken immediately to target both primary and secondary melanoma
      prevention messages to Hispanic communities.

PMID- 16429454
TI  - Synthesis and antibacterial activity of 1beta-methyl-2-[5-(1,2-disubstituted
      ethyl)pyrrolidin-3-ylthio]carbapenem derivatives.
AB  - The synthesis of a new series of 1beta-methylcarbapenems having a 5-(1,2
      disubstituted ethyl) pyrrolidine moiety is described. Their in vitro
      antibacterial activities against both Gram-positive and Gram-negative bacteria
      were tested and the effect of the substituent on the pyrrolidine ring was
      investigated. A particular compound IIIf having a 1-methoxyimino-2-carbamoylethyl
      substituted moiety showed the most potent antibacterial activity.

PMID- 16429455
TI  - Database of two-dimensional polyacrylamide gel electrophoresis of proteins
      labeled with CyDye DIGE Fluor saturation dye.
AB  - CyDye DIGE Fluor saturation dye (saturation dye, GE Healthcare Amersham
      Biosciences) enables highly sensitive 2-D PAGE. As the dye reacts with all
      reduced cysteine thiols, 2-D PAGE can be performed with a lower amount of
      protein, compared with CyDye DIGE Fluor minimal dye (GE Healthcare Amersham
      Biosciences), the sensitivity of which is equivalent to that of silver staining.
      We constructed a 2-D map of the saturation dye-labeled proteins of a liver cancer
      cell line (HepG2) and identified by MS 92 proteins corresponding to 123 protein
      spots. Functional classification revealed that the identified proteins had
      chaperone, protein binding, nucleotide binding, metal ion binding, isomerase
      activity, and motor activity. The functional distribution and the cysteine
      contents of the proteins were similar to those in the most comprehensive 2-D
      database of hepatoma cells (Seow et al.., Electrophoresis 2000, 21, 1787-1813),
      where silver staining was used for protein visualization. Hierarchical clustering
      on the basis of the quantitative expression profiles of the 123 characterized
      spots labeled with two charge- and mass-matched saturation dyes (Cy3 and Cy5)
      discriminated between nine hepatocellular carcinoma cell lines and primary
      cultured hepatocytes from five individuals, suggesting the utility of saturation
      dye and our database for proteomic studies of liver cancer.

PMID- 16429456
TI  - Use of a fluorescent internal protein standard to achieve quantitative two
      dimensional gel electrophoresis.
AB  - 2-DE is a powerful separation method for complex protein mixtures. However, large
      intergel variations in spot intensity limit its use for quantitative proteomics
      studies. To address this issue, we developed a fluorescent internal protein
      standard for use in 2-DE analysis. Protein samples are spiked with an Alexa
      labeled internal standard (ALIS) prior to separation with 2-DE. Due to the high
      extinction coefficient of the Alexa-fluor, incorporation of 0.1% of total protein
      is sufficient to allow visualization of the internal standard yet low enough to
      avoid interference in subsequent quantification and identification steps.
      Following 2-DE, total proteins are visualized with fluorescent
      postelectrophoretic stains spectrally separated from ALIS. Four protein stains,
      Deep Purple, Sulforhodamine G, ruthenium II-tris(bathophenanthroline disulfonate)
      (RuTBS), and SYPRO Ruby, including improved purification and staining protocols
      for RuTBS and ten-fold dilutions of SYPRO Ruby were evaluated. All staining
      protocols were compatible with the ALIS method and had similar LODs (1-4 ng) and
      dynamic ranges (10(3)). ALIS is a powerful normalization method for quantitative
      2-DE which avoids potential problems associated with dual spot migration patterns
      observed in the DIGE method. Furthermore, ALIS provides significantly improved
      normality in the distribution of spot abundance-variance compared to
      normalization through division by the total spot volume.

PMID- 16429457
TI  - Alpha tocopherol supplementation elevates plasma apolipoprotein A1 isoforms in
      normal healthy subjects.
AB  - Plasma alpha-tocopherol (AT) concentrations are inversely related to
      cardiovascular (CV) risk; however, intervention studies with AT have failed to
      show any consistent benefit against CV disease (CVD). Proteomics offers the
      opportunity to examine novel effects of AT supplementation on protein expression
      and therefore improve our understanding of the physiological roles of AT. Thus,
      to investigate the effects of AT supplementation on the plasma proteome of
      healthy subjects we have undertaken a double-blind, randomised, parallel design
      supplementation study in which healthy subjects (n = 32; 11 male and 21 female)
      consumed AT supplements (134 or 268 mg/day) or placebo capsules for up to 28
      days. Plasma samples were obtained before supplementation and after 14 and 28
      days of supplementation for analysis of changes in the plasma proteome using 2-DE
      and MALDI-MS. Using semiquantitative proteomics, we observed that
      proapolipoprotein A1 (identified by MS and Western blotting) was altered at least
      two-fold. Using quantitative ELISA techniques, we confirmed a significant
      increase in plasma apolipoprotein A1 concentration following supplementation with
      AT which was both time and dose dependent (p < 0.01 after 28 days supplementation
      with 268 mg AT/day). These data demonstrate the time and dose sensitivity of the
      plasma proteome to AT supplementation.

PMID- 16429458
TI  - Proteomic and SAGE profiling of murine melanoma progression indicates the
      reduction of proteins responsible for ROS degradation.
AB  - Using 2-DE of total cell protein extracts, we compared soluble proteins from
      murine melanoma lines Tm1 and Tm5 with proteins from the nontumoral cell melan-a
      from which they were derived. Seventy-one of the 452 spots (average) detected
      with CBB were differentially accumulated, i.e., increased or decreased twofold.
      Forty-four spots were identified by PMF/MALDI-TOF, 15 with increased and 29 with
      decreased protein levels. SAGE showed that 17/34 (50%) of the differentially
      accumulated proteins, pI range 4-7, presented similar differences at the mRNA
      level. Major reductions in protein were observed in tumor cells of proteins that
      degrade reactive oxygen species (ROS). Decreases of > or = twofold in GST,
      superoxide dismutase, aldehyde dehydrogenase, thioredoxin, peroxiredoxin 2, and
      peroxiredoxin 6 protein were observed. SAGE indicated the reduction of other
      proteins involved in ROS degradation. As expected, the accumulation of exogenous
      peroxides was significantly higher in the tumor cells while the levels of
      glutathionylation were two times lower in the tumor cells compared to melan-a.
      The differential accumulation of proteins involved in oncogene/tumor suppressor
      pathways was observed. Melanoma cells can favor survival pathways activated by
      ROS by inhibiting p53 pathways and activation of Ras and c-myc pathways.

PMID- 16429459
TI  - Changes in cod muscle proteins during frozen storage revealed by proteome
      analysis and multivariate data analysis.
AB  - Multivariate data analysis has been combined with proteomics to enhance the
      recovery of information from 2-DE of cod muscle proteins during different storage
      conditions. Proteins were extracted according to 11 different storage conditions
      and samples were resolved by 2-DE. Data generated by 2-DE was subjected to
      principal component analysis (PCA) and discriminant partial least squares
      regression (DPLSR). Applying PCA to 2-DE data revealed the samples to form groups
      according to frozen storage time, whereas differences due to different storage
      temperatures or chilled storage in modified atmosphere packing did not lead to
      distinct changes in protein pattern. Applying DPLSR to the 2-DE data enabled the
      selection of protein spots critical for differentiation between 3 and 6 months
      frozen storage with 12 months frozen storage. Some of these protein spots have
      been identified by MS/MS, revealing myosin light chain 1, 2 and 3, triose
      phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, aldolase A and two
      alpha-actin fragments, and a nuclease diphosphate kinase B fragment to change in
      concentration, during frozen storage. Application of proteomics, multivariate
      data analysis and MS/MS to analyse protein changes in cod muscle proteins during
      storage has revealed new knowledge on the issue and enables a better
      understanding of biochemical processes occurring.

PMID- 16429460
TI  - Human plasma proteome analysis by reversed sequence database search and molecular
      weight correlation based on a bacterial proteome analysis.
AB  - In shotgun proteomics, proteins can be fractionated by 1-D gel electrophoresis
      and digested into peptides, followed by liquid chromatography to separate the
      peptide mixture. Mass spectrometry generates hundreds of thousands of tandem mass
      spectra from these fractions, and proteins are identified by database searching.
      However, the search scores are usually not sufficient to distinguish the correct
      peptides. In this study, we propose a confident protein identification method for
      high-throughput analysis of human proteome. To build a filtering protocol in
      database search, we chose Pseudomonas putida KT2440 as a reference because this
      bacterial proteome contains fewer modifications and is simpler than the human
      proteome. First, the P. putida KT2440 proteome was filtered by reversed sequence
      database search and correlated by the molecular weight in 1-D-gel band positions.
      The characterization protocol was then applied to determine the criteria for
      clustering of the human plasma proteome into three different groups. This protein
      filtering method, based on bacterial proteome data analysis, represents a rapid
      way to generate higher confidence protein list of the human proteome, which
      includes some of heavily modified and cleaved proteins.

PMID- 16429461
TI  - Protein nanoarray on Prolinker surface constructed by atomic force microscopy dip
      pen nanolithography for analysis of protein interaction.
AB  - Protein nanoarrays are addressable ensembles of nano-scale protein domain on
      solid surfaces. This method can serve as a useful platform for ultraminiaturized
      bioanalysis. In this study, we investigated single molecular nanopatterning and
      molecular interaction of proteins that were immobilized on Prolinker surface of
      gold-coated silicon wafer by using dip-pen nanolithography (DPN) method. Contact
      force and humidity were optimized at 0.01 nN and 80%, respectively. The domain
      features of protein nanoarrays were developed at the contact time of 5 s. The
      optimized conditions for the nanoarray process were applied to create protein
      nanoarray using integrin alpha(v)beta3 and angiogenin. Constructed protein
      nanoarrays using integrin alpha(v)beta3 have single molecular monolayer with
      regular domain shape (height 15 +/- 5 nm). The changed height value due to the
      single molecular interaction between integrin alpha(v)beta3 and vitronectin was
      approximately 30 +/- 5 nm on Prolinker surface as measured with atomic force
      microscopy tip. Taken together, these results suggest that protein nanoarray on
      Prolinker surface fabricated by well-controlled DPN process can be used to
      analyze single molecular interaction of protein.

PMID- 16429462
TI  - Alteration of the glutamate and GABA transporters in the hippocampus of the
      Niemann-Pick disease, type C mouse using proteomic analysis.
AB  - Niemann-Pick disease type C (NPC) is a fatal autosomal recessive cholesterol
      disorder characterized by severe progressive neurodegeneration. To unveil the
      mechanism of neurodegeneration, proteomic and morphological approaches were
      applied to the hippocampus in NPC -/- mouse. Two-DE was utilized to resolve the
      hippocampal protein expression profiles of 4- and 8-week-old NPC +/+ and -/-
      mice. Differentially expressed protein spots were identified by MALDI-TOF MS and
      database searching. At 4 weeks of age, there was no significant difference in
      protein profiles between NPC +/+ and -/- mice. However, at the age of 8 weeks,
      NPC +/+ and -/- mice showed marked difference in protein expressions. Among
      these, glutamate receptor 2 precursor was identified. The immunohistochemical
      study on neurotransporters showed that glial GABA transporter (GAT-3) increased
      in both 4- and 8-week-old NPC -/- mouse and glutamic acid decarboxylase (GAD-6)
      increased in 8-week-old NPC -/- mouse. Glial glutamate transporter, excitatory
      amino acids carrier-1 (EAAC1), decreased in 8-week-old NPC -/- mouse. In
      conclusion, our data may provide insight into the understanding of the basic
      mechanism through perturbation of protein networks and neurotransporter systems
      in a single gene knockout model of NPC disease.

PMID- 16429463
TI  - Proteomic analysis of growth phase-dependent proteins of Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae is an important human pathogen that causes a variety of
      diseases, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis,
      in both adults and children. The global pattern of growth phase-dependent protein
      expression of S. pneumoniae during in vitro culture was analyzed using 2-DE
      combined with MALDI-TOF MS and LC/ESI-MS/MS. Several protein production patterns
      were observed at four time points throughout the growth stage, although some
      protein levels did not change significantly. We focused on the switch in protein
      expression at the transition from log growth phase to stationary phase. Proteins
      that were significantly induced or repressed at this point are likely to be
      involved in central intermediary metabolism, amino acid synthesis, nucleotide,
      and fatty acid metabolism, cell wall synthesis, protein degradation, and stress
      responses. This global expression profiling approach has revealed previously
      unrecognized relationships between proteins in the life of this pathogen.

PMID- 16429464
TI  - Population proteomics: an emerging discipline to study metapopulation ecology.
AB  - Proteomics research has developed until recently in a relative isolation from
      other fast-moving disciplines such as ecology and evolution. This is unfortunate
      since applying proteomics to these disciplines has apparently the potential to
      open new perspectives. The huge majority of species indeed exhibit over their
      entire geographic range a metapopulation structure, occupying habitats that are
      fragmented and heterogeneous in space and/or through time. Traditionally,
      population genetics is the main tool used to studying metatopulations, as it
      describes the spatial structure of populations and the level of gene flow between
      them. In this Viewpoint, we present the reasons why we think that proteomics,
      because of the level of integration it promotes, has the potential to resolve
      interesting issues specific to metapopulation biology and adaptive processes.

PMID- 16429465
TI  - Is protein overlap in two-dimensional gels a serious practical problem?
AB  - In a recently published article, Campostrini et al. [Proteomics 2005, 5, 2385
      2395] raised questions regarding the utility of 2-D gels in proteomics research.
      We believe that the authors have overlooked several key issues including the
      dynamic range of protein expression and the sensitivity of the analytical methods
      used to explore a proteome. We argue that 2-D gels have and will continue to
      provide meaningful quantitative data when applied to proteomic analysis and that
      the practical significance of spot overlap has been overstated.

PMID- 16429466
TI  - Mesoporous hybrid thin films: the physics and chemistry beneath.
AB  - Mesoporous films containing organic or biological functions within an organised
      array of cavities are produced by combining sol-gel, self-assembly of
      supramolecular templates and surface chemistry. This paper reviews the essential
      physics and chemical concepts behind the synthesis of these complex
      multifunctional materials.

PMID- 16429467
TI  - Conducting poly(aniline) nanotubes and nanofibers: controlled synthesis and
      application in lithium/poly(aniline) rechargeable batteries.
AB  - The primary aim of this work was to synthesize aligned perchloric-acid-doped
      poly(aniline) (HClO(4)-doped PANI) nanotubes by a simple alumina template method
      and to investigate their application in lithium/poly(aniline) rechargeable
      batteries. Powder X-ray diffraction analysis (XRD), scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), and Fourier transform infrared
      (FTIR) analysis were used to characterize the nanostructures obtained. The second
      aim addressed the preparation of HClO(4)-doped PANI microspheres and nanofibers
      on a large scale through a modified spraying technique, since the template
      synthesis has limitations in mass production. The present synthesis methods are
      simple and can be extended to the preparation of a broad range of one-dimensional
      conductive polymers. Furthermore, electrochemical measurements showed that the as
      prepared HClO(4)-doped PANI nanotubes exhibit better electrode performances than
      their commercial counterparts because they possess more active sites, higher
      conductivity, and relative flexibility. This indicates that HClO(4)-doped
      poly(aniline) nanomaterials are promising in the application of lithium/polymer
      rechargeable batteries.

PMID- 16429468
TI  - Effects of dipolar interactions on linear and nonlinear optical properties of
      multichromophore assemblies: a case study.
AB  - Interchromophore interactions in flexible multidipolar structures for nonlinear
      optics were addressed by a combined experimental and theoretical study on two
      series of one-, two-, and three-chromophore systems in which identical push-pull
      chromophores are assembled through covalent and flexible linkers in close
      proximity. The photophysical and nonlinear optical properties (quadratic
      hyperpolarizability) of the multichromophore systems were investigated and
      compared to those of the monomeric chromophores. Multimers have larger dipole
      moments than their monomeric analogues, that is, the dipolar subchromophores self
      orientate within the multimeric structures. This effect was found to depend on
      the intersubchromophore distance in a nontrivial manner, which confirms that
      molecular engineering of such flexible systems is more complex than in completely
      geometrically controlled systems. Electric-field-induced second-harmonic
      generation (EFISHG) measurements in solution revealed increased figures of merit
      as compared to the monomeric analogue. This effect increases with increasing
      number and polarity of the individual subchromophores in the nanoassembly and
      increasing spacing between dipolar subchromophores. Experimental results are
      interpreted by a theoretical model for interacting polar and polarizable
      chromophores. The properties of multidipolar assemblies are shown to be related
      to the relative orientation of chromophores, which is imposed by interchromophore
      interactions. The supramolecular structure is thus a result of self-organization.
      The proposed theoretical model was also used to predict the properties of
      multichromophore structures made up of more polar and polarizable push-pull
      chromophores, and showed that stronger interchromophore interactions can heavily
      affect the individual optical responses. This suggests new routes for engineering
      highly NLO responsive multichromophore systems.

PMID- 16429469
TI  - Systematic investigation of the formation of 1D alpha-Si(3)N(4) nanostructures by
      using a thermal-decomposition/nitridation process.
AB  - This article describes a simple thermal-decomposition/nitridation method for the
      large-scale synthesis of 1D alpha-Si(3)N(4) nanostructures, such as millimeter
      scale microribbons, nanosaws, nanoribbons, and nanowires. These nanostructures
      are systematically investigated by checking the product deposited at different
      areas by using powder X-ray diffraction, scanning electron microscopy,
      transmission electron microscopy, and electron energy loss spectroscopy. Studies
      show that all these nanostructures have a single-crystalline nature and
      predominantely grow along the [011] direction. These 1D nanostructures are formed
      by thermal decomposition, followed by the nitridation of SiO.

PMID- 16429470
TI  - Insertion, reduction, and carbon-carbon coupling induced by monomeric aluminum
      hydride compounds bearing substituted pyrrolyl ligands.
AB  - A monomeric aluminum hydride complex bearing substituted pyrrolyl ligands,
      AlH[C(4)H(3)N(CH(2)NMe(2))-2](2) (1), was synthesized and structurally
      characterized. To further confirm the presence of Al--H bonds, the compound
      AlD[C(4)H(3)N(CH(2)NMe(2))-2](2) ([D]1) was synthesized by reacting LiAlD(4) with
      [C(4)H(4)N(CH(2)NMe(2))-2]. Compound 1 and [D]1 react with phenyl isothiocyanate
      yielding Al[C(4)H(3)N(CH(2)NMe(2))-2](2)[eta(3)-SCHNPh] (2) and
      Al[C(4)H(3)N(CH(2)NMe(2))-2](2)[eta(3)-SCDNPh] ([D]2) by insertion. The reactions
      of 1 with 9-fluorenone and benzophenone generated the unusual aluminum alkoxide
      complexes 3 and 4, respectively, through intramolecular proton abstraction and C
      C coupling. A mechanistic study shows that 9-fluorenone coordinates to [D]1 and
      releases one equivalent of HD followed by C-C coupling and hydride transfer to
      yield the final product. Reduction of benzil with 1 affords aluminum enediolate
      complex 5 in moderate yield. Mechanistic studies also showed that the benzil was
      inserted into the aluminum hydride bond of [D]1 through hydroalumination followed
      by proton transfer to generate the final product [D]5. All new complexes have
      been characterized by (1)H and (13)C NMR spectroscopy and X-ray crystallography.

PMID- 16429471
TI  - A new methodology for the synthesis of fluorinated exo-glycals and their time
      dependent inhibition of UDP-galactopyranose mutase.
AB  - Fluorinated carbohydrates constitute a very important class of mechanistic probes
      for glycosyl-processing enzymes. In this study, we describe the first synthesis
      of fluorinated and phosphonylated exo-glycals and their corresponding nucleotide
      sugars in the galactofuranose series. The synthetic protocol that we have
      developed is a Selectfluor-mediated fluorination/elimination sequence on
      phosphonylated exo-glycals, and it offers a new entry into fluorinated
      carbohydrate chemistry. The challenging E/Z stereochemical assignment of the
      resulting tetrasubstituted alkenes, which bear an alkoxy, an alkyl, a fluoro, and
      a phosphonyl group, has been achieved through NMR experiments. The corresponding
      (E)- and (Z)-nucleotide fluorosugars have been prepared and tested as inhibitors
      of UDP-galactopyranose mutase (UGM). UGM is a flavoenzyme that catalyzes the
      isomerization of uridine diphosphate(UDP)-galactopyranose into UDP
      galactofuranose, a key step of the biosynthesis of important mycobacterial cell
      wall glycoconjugates. The two diastereomeric molecules were found to display time
      dependent inactivation of UGM, as expected from preliminary results using non
      fluorinated exo-glycal nucleotides. The inhibitory properties of the two
      fluorinated molecules led us to suggest that the inactivation mechanism proceeds
      through two-electron processes, despite the presence of the flavin cofactor
      within the UGM catalytic site.

PMID- 16429472
TI  - Electronic interactions in a new pi-extended tetrathiafulvalene dimer.
AB  - The first pi-extended tetrathiafulvalene (exTTF) dimer in which the two exTTF
      units are covalently connected by 1,3-dithiole rings has been obtained in a
      multistep synthetic procedure involving the Ullmann cross-coupling reaction by
      using copper(I) thiophene-2-carboxylate (CuTC). The electronic spectrum reveals a
      significant electronic interaction between the exTTF units. The electrochemical
      study carried out by cyclic voltammetry in solution and in thin-layer conditions,
      and the electrochemical simulation and spectroelectrochemical (SEC) measurements
      confirm the electronic communication and show that the oxidation of dimer 14
      occurs as two consecutive 2 e(-) processes D(0)-D(0)-->D(2+)-D(0)-->D(2+)-D(2+).
      Theoretical calculations, performed at the B3P86/6-31G* level, confirm the
      experimental findings and predict that 14(2+) exists as a delocalized D(.+)-D(.+)
      species in the gas phase and as a localized D(2+)-D(0) species in solution
      (CH(3)CN or CH(2)Cl(2)). Oxidation of 14(2+) forms the tetracation 14(4+) which
      is constituted by two aromatic anthracene units bearing four aromatic, almost
      orthogonal 1,3-dithiolium cations.

PMID- 16429473
TI  - Enzyme-free amperometric sensing of glucose by using gold nanoparticles.
AB  - A nonenzymatic electrochemical method is described for the detection of glucose
      by using gold (Au) nanoparticles self-assembled on a three-dimensional (3D)
      silicate network obtained by using sol-gel processes. The nanosized Au particles
      have been self-assembled on the thiol tail groups of the silicate network and
      enlarged by hydroxylamine. The Au nanoparticles efficiently catalyze the
      oxidation of glucose at less-positive potential (0.16 V) in phosphate buffer
      solution (pH 9.2) in the absence of any enzymes or redox mediators. The Au
      nanoparticle-modified transducer (MPTS-nAuE) was successfully used for the
      amperometric sensing of glucose and it showed excellent sensitivity with a
      detection limit of 50 nM. The common interfering agent ascorbate (AA) does not
      interfere with the detection of glucose. The MPTS-nAuE transducer showed
      individual voltammetric responses for glucose and AA. This transducer responded
      linearly to glucose in the range of 0-8 mM and the sensitivity of the transducer
      was found to be 0.179 nA cm(-2) nM(-1). Excellent reproducibility, and long-term
      storage and operational stability was observed for this transducer.

PMID- 16429474
TI  - Synthesis, crystal structures, linear and nonlinear optical properties, and
      theoretical studies of (p-R-phenyl)-, (p-R-phenylethynyl)-, and (E)-[2-(p-R
      phenyl)ethenyl]dimesitylboranes and related compounds.
AB  - The (p-R-phenyl)dimesitylboranes (R=Me(2)N, MeO, MeS, Br, I), (p-R
      phenylethynyl)dimesitylboranes (R=Me(2)N, MeO, MeS, H), (E)-[2-(p-R
      phenyl)ethenyl]dimesitylboranes (R=Me(2)N, H(2)N, MeO, MeS, H, CN, NO(2)), (E)-[2
      (2-thienyl)ethenyl]dimesitylborane, and (E)-[2-(o
      carboranyl)ethenyl]dimesitylborane have been prepared through the reaction of the
      appropriate p-R-phenyl- and p-R-phenylethynyllithium reagents with dimesitylboron
      fluoride and by hydroboration of the appropriate p-R-phenylacetylene, 2
      ethynylthiophene, and o-ethynylcarborane with dimesitylborane. Their UV/Vis
      absorption and emission spectra have been recorded in a range of solvents with
      the fluorescence maxima of the donor-substituted compounds in particular
      exhibiting large bathochromic shifts in highly polar solvents, indicative of
      charge transfer leading to large dipole moments in the excited state. The
      molecular structures of the (p-R-phenyl)dimesitylboranes (R=Me(2)N, MeO, MeS, Br,
      I), the (E)-[2-(p-R-phenyl)ethenyl]dimesitylboranes (R=Me(2)N, H(2)N MeO, MeS,
      H), (p-R-phenylethynyl)dimesitylborane (R=Me(2)N), and (E)-[2-(2
      thienyl)ethenyl]dimesitylborane, which have been determined from single-crystal X
      ray diffraction measurements, offer evidence of increased conjugation in the
      ground state with increased donor strength of the R substituent. Their first- and
      second-order molecular hyperpolarizabilities have been obtained from EFISH and
      THG measurements, the first-order hyperpolarizabilities being largest for the
      strongest R-substituent donors. AM1 calculations have been performed on these
      compounds, showing reasonable agreement with the experimentally obtained bond
      lengths and hyperpolarizabilities, as well as on several related hypothetical
      compounds containing multiple C==C bonds, most of which are proposed to have even
      larger hyperpolarizabilities.

PMID- 16429475
TI  - The synthesis and characterization of all diastereomers of a linear symmetrically
      fused Tris-Troger's base analogue: new chiral cleft compounds.
AB  - The synthesis and characterization of all diastereomers of a linear symmetrically
      fused tris-Troger's base analogue are described. The diastereomers are
      unambiguously assigned as syn-anti 1 a, anti-anti 1 b, and syn-syn 1 c isomers,
      by using X-ray diffraction analysis and NMR spectroscopy. For the first time, the
      anti-anti and the syn-syn diastereomers of a linear symmetrically fused tris
      Troger's base analogue have been synthesized. Molecules 1 a and 1 c are new cleft
      compounds and analysis of compound 1 a in the solid state shows inclusion of one
      molecule of CH(2)Cl(2) in the larger aromatic cleft, whereas in isomer 1 c
      disordered solvent molecules are trapped in the extended aromatic cleft.
      Furthermore, in the solid state, isomer 1 c forms infinite open channels along
      one of the crystallographic axes and perpendicular to this axis there are
      infinitely extending "wedged-ravines". Importantly, each of the diastereomers 1 a
      c is resistant to inversion at the stereogenic nitrogen atoms under strongly and
      weakly acidic conditions in the range from room temperature (RT) to 95 degrees C.
      This observed configurational stability at the stereogenic nitrogens of 1 a-c is
      unique for analogues of Troger's base in general to date. Finally, the ratio of
      cleft compounds 1 a and 1 c significantly increased relative to cavity compound 1
      b when ammonium chloride was used as an additive in the Troger's base
      condensation to 1 a-c suggesting a templating effect of the ammonium ion.

PMID- 16429476
TI  - Density functional studies on the Nazarov reaction involving cyclic systems.
AB  - Density functional theory (DFT) has been used to define the energy profiles of
      the Nazarov reaction involving cyclic systems. The calculations were carried out
      at the B3LYP/6-311G** level of theory and the solvent (dichloromethane)
      contribution was estimated by using the recently developed SM5.43R solvation
      model. DFT calculations were first carried out to determine the energy profiles
      associated with the electrocyclization reactions of 3-hydroxy- and 3
      ethoxypentadienyl cations in which one of the double bonds is embedded in O
      heterocyclic and carbocyclic systems. In particular, the effects on the reaction
      rate of modifications to the substrate, as well as the presence of the heteroatom
      in the cycle, have been investigated. The torquoselectivity of the
      electrocyclization reaction was then explored with substituted O-heterocycles to
      understand the factors that control the stereochemical outcome of the process
      that preferentially provides 2,5-trans-disubstituted products. These DFT-based
      results rationally explain most of the experimental observations related to the
      Nazarov reaction of the substrates herein investigated and could be useful in the
      rational interpretation, and likely in the prediction, of the outcome of Nazarov
      reactions involving other cyclic systems.

PMID- 16429477
TI  - Results of L-[1-13C]phenylalanine breath test with air isotope ratio mass
      spectrometry can reflect the activity of phenylalanine hydroxylase in cirrhotic
      rat liver.
AB  - The L-[1-13C]phenylalanine breath test (PheBT) could potentially advance the
      evaluation of hepatocyte function and liver functional reserve. However, because
      the factors influencing PheBT results have not been clarified, the clinical
      application of the test has been limited. This study investigated the
      relationship between the parameters of PheBT, performed with air isotope ratio
      mass spectrometry, and the activity of phenylalanine hydroxylase (PAH), the
      phenylalanine metabolism rate-limiting enzyme, in rat liver, and proposes valid
      parameters for the assessment of liver function. Chronic injury to the liver was
      induced by the administration of CCl4 to male Sprague-Dawley rats for either 8 or
      12 weeks. Livers from rats in the two cirrhotic groups were discolored, enlarged
      and roughly textured, with cells filled with fat granules of various sizes,
      pseudolobuli formations, and regenerated tubercles. Of the 12 parameters tested,
      only the unit liver weight (LW) breath test parameters, including the maximum
      abundance of 13C in breath (13Cmax/LW), 13C abundance in breaths 2 and 7 min
      after administration of L-[1-(13)C]phenylalanine (13C-phe) (13C2/LW and 13C7/LW),
      cumulative 13C excretion 10 and 30 min after 13C-phe administration (AUC10/LW and
      AUC30/LW), and the 13C excretion rate constant (PheBT-k/LW) were significantly
      affected in the chronic liver injury groups. There was no significant difference
      in the total PAH activity in liver among the three groups, but there was
      significant difference in unit LW PAH activity. Total PAH activity in the liver
      was significantly correlated with 13Cmax, 13C2, 13C7, AUC10, AUC30 and PheBT-k,
      while the unit LW PAH activity was significantly correlated with 13Cmax/LW,
      13C2/LW, 13C7/LW, AUC10/LW, AUC30/LW and PheBT-k/LW. PheBT-k/LW was also
      correlated with biochemical indices that are used to assess liver function. The
      present findings indicate that the PheBT results based on air isotope ratio mass
      spectrometry can quantitatively reflect the change in total PAH activity in the
      livers of chronically injured rats. PheBT-k and PheBT-k/LW are the most sensitive
      among the test parameters, and can be used to assess liver functional reserve and
      hepatocyte damage at the molecular level.

PMID- 16429478
TI  - The one-electron oxidation of [HCCOCC]- to form neutral HCCOCC, and the
      subsequent rearrangement of HCCOCC to form HCCCCO. An experimental and
      computational study.
AB  - The singlet anion [HCCOCC]- may be made in the source of a VG ZAB 2HF mass
      spectrometer by the reaction between F- (from SF6) and H-C[triple chemical bond]C
      O-C[triple chemical bond]C-TMS. Vertical (Franck-Condon) one-electron oxidation
      of [HCCOCC]- in the first collision cell produces doublet neutral HCCOCC. A
      combination of experiment and molecular modelling [at the CCSD(T)/aug-cc
      pVDZ//B3LYP/6-31 + G(d) level of theory] provides data which are consistent with
      some HCCOCC neutrals being stable for the duration of the neutralisation
      reionisation experiment, while others rearrange to form the decomposing doublet
      neutral HCCCCO.

PMID- 16429479
TI  - Effects of chemical lipid extraction and arithmetic lipid correction on stable
      isotope ratios of fish tissues.
AB  - For accurate interpretation of fish trophodynamics from carbon stable isotope
      data it is necessary to extract tissue lipids. This is because lipid content
      varies within and among tissues in both space and time, and because lipids are
      13C-depleted relative to proteins. However, lipid extraction may affect delta15N,
      thus requiring costly and time-consuming separation of delta13C and delta15N
      analyses. These problems have prompted the development of arithmetic correction
      techniques for delta13C, but the techniques and their underlying assumptions have
      not been systematically tested. This study compared the effects of lipid
      extraction and arithmetic correction techniques on delta13C and delta15N of
      European sea bass (Dicentrarchus labrax) tissues. Following Folch lipid
      extraction from muscle and liver, there was a mean increase in delta15N of 0.77
      per thousand, but enrichment varied with lipid content such that effects on
      delta15N were hard to predict. Changes in delta13C and C:N between untreated and
      lipid-extracted samples reflected the quantity of lipid removed. The arithmetic
      correction techniques of mass balance and lipid correction were sensitive to the
      C:N of the lipid-extracted tissue and to the assumed depletion of lipid delta13C
      relative to protein delta13C. However, the mass balance approach was appropriate
      for the mathematical correction of bulk tissue data in most circumstances,
      provided that the C:N of lipid-extracted tissue could be determined for a small
      proportion of samples. Application of mass balance arithmetic correction can lead
      to significant time and cost savings in trophodynamic studies, because the
      majority of delta13C and delta15N analyses would not need to be run separately.

PMID- 16429480
TI  - Characterization of unusual alkenones and alkyl alkenoates by electron ionization
      gas chromatography/mass spectrometry.
AB  - Unusual long-chain, diunsaturated alkenones and alkyl alkenoates exhibiting
      double bonds separated by three methylene units instead of the more usual five
      were characterized by electron ionization (EI) gas chromatography/mass
      spectrometry. In a first step, the positions of the double bonds of these
      compounds (isolated from Holocene Black Sea sediments) were confirmed after OsO4
      treatment and silylation. Mass spectra of the resulting tetratrimethylsilyloxy
      derivatives allowed unambiguous determination of the positions of unsaturations.
      The EI mass spectra of the non-derivatized compounds were then compared with
      those of the alkenones and alkyl alkenoates having double bonds separated by five
      methylene units. Specific fragment ions resulting from gamma-H rearrangements
      were found to be prominent in EI mass spectra of these unusual 'Black Sea'
      diunsaturated alkenones and alkyl alkenoates. These fragment ions can be used to
      characterize these compounds in natural samples without the need for laborious
      derivatization treatments.

PMID- 16429481
TI  - Studies of gas-phase fragmentation reactions of [Pd(PPh3)2(OCOR)]+ by
      electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Gas-phase fragmentation reactions of [Pd(PPh3)2(OCOR)]+ (R = H, CH3, CD3, C2H5, n
      C3H7, n-C6H13 and C6H5) were studied by electrospray ionization Fourier transform
      ion cyclotron resonance mass spectrometry (ESI-FTICRMS). In sustained off
      resonance irradiation collision-activated dissociation (SORI-CAD) experiments,
      the complexes all dissociated to yield the same product ion at m/z 629.1. We
      propose that the fragmentation pathway occurs through the elimination of RCOOH
      and a palladium(IV) hydride intermediate. Semi-empirical (PM3) calculations shed
      light on the mechanism for the fragmentation reactions of these compounds. The
      results of deuterium-labeling experiments indicate that the protons of RCOOH lost
      from [Pd(PPh3)2(OCR)]+ originate from the phenyl in the triphenylphosphine
      ligand. [Pd(PPh3)2(OCOH)]+ undergoes two competitive pathways in SORI-CAD
      experiments, one of which is similar to that of [Pd(PPh3)2(OCOR)]+ (R = CH3, CD3,
      C2H5, n-C3H7, n-C6H13 and C6H5), and the other involves decarboxylation. The
      present study demonstrates that MS could play an important role in studying the
      gas-phase chemistry of palladium hydrides.

PMID- 16429482
TI  - Orexin-A is composed of a highly conserved C-terminal and a specific, hydrophilic
      N-terminal region, revealing the structural basis of specific recognition by the
      orexin-1 receptor.
AB  - Orexins-A and B, also called hypocretins-1 and 2, respectively, are neuropeptides
      that regulate feeding and sleep-wakefulness by binding to two orphan G protein
      coupled receptors named orexin-1 (OX(1)R) and orexin-2 (OX(2)R). The sequences
      and functions of orexins-A and B are similar to each other, but the high sequence
      homology (68%) is limited in their C-terminal half regions (residues 15-33). The
      sequence of the N-terminal half region of orexin-A (residues 1-14), containing
      two disulfide bonds, is very different from that of orexin-B. The structure of
      orexin-A was determined using two-dimensional homonuclear and (15)N and (13)C
      natural abundance heteronuclear NMR experiments. Orexin-A had a compact
      conformation in the N-terminal half region, which contained a short helix
      (III:Cys6-Gln9) and was fixed by the two disulfide bonds, and a helix-turn-helix
      conformation (I:Leu16-Ala23 and II:Asn25-Thr32) in the remaining C-terminal half
      region. The C-terminal half region had both hydrophobic and hydrophilic residues,
      which existed on separate surfaces to provide an amphipathic character in helices
      I and II. The nine residues on the hydrophobic surface are also well conserved in
      orexin-B, and it was reported that the substitution of each of them with alanine
      resulted in a significant drop in the functional potency at the receptors.
      Therefore, we suggest that they form the surface responsible for the main
      hydrophobic interaction with the receptors. On the other hand, the residues on
      the hydrophilic surface, together with the hydrophilic residues in the N-terminal
      half region that form a cluster, are known to make only small contributions to
      the binding to the receptors through similar alanine-scan experiments. However,
      since our structure of orexin-A showed that large conformational and
      electrostatical differences between orexins-A and B were rather concentrated in
      the N-terminal half regions, we suggest that the region of orexin-A is important
      for the preference for orexin-A of OX(1)R.

PMID- 16429483
TI  - Rate enhancements and the mechanism of oxime-mediated reactivation.

PMID- 16429484
TI  - Acetylcholinesterase: pivotal roles of its long omega loop (Cys69-Cys96) in
      regulating substrate binding.
AB  - Acetycholinesterase (AChE) hydrolyses neuronal and non-neuronal acetylcholine
      (ACh) very efficiently, and this possibly prevents the mitogenic action of ACh.
      AChE activity was measured in twenty-three samples of non-small lung carcinomas
      (NSLCs) and in their adjacent normal tissue. Twelve out of them were
      adenocarcinoma (AC), 6 squamous cell carcinoma (SCC) and 5 large cell carcinoma
      (LCC). The mean AChE activity in healthy lung was 10.95 +/- 6.90 mU/mg; in AC,
      8.13 +/- 5.84 (p = 0.774); in LCC, 9.57 +/- 7.47 mU/mg (p = 0.063); and in SCC,
      2.25 +/- 0.67 (p = 0.028). AChE dimers and monomers were identified in healthy
      and tumoral tissues and their contribution was not affected by cancer. The
      fraction of AChE molecules reacting with the lectin Con A increased in squamous
      cell carcinoma when compared to control, adenocarcinoma and large cell carcinoma
      specimens. The increased level of ACh in lung cancers, resulting from the fall of
      AChE activity, may collaborate to lung cancer growth.

PMID- 16429485
TI  - Acetylcholinesterase biogenesis is impaired in lung cancer tissues.
AB  - Studies cited by Cowan et al. [J. Appl. Toxicol. 23, 177 (2003)] indicate
      existence of inflammatory and cholinergic pathways in both nerve agents and
      sulfur mustard (HD) injury. Increase in AChE synthesis and neurite extension was
      noted after exposure to HD [K.W. Lanks et al., Exp. Cell Res. 355 (1975)].
      Moreover, anti-inflammatory drugs reduce the dermal, respiratory and ocular
      damage caused by exposure to HD. On the other hand, recent studies have noted the
      involvement of neuro-inflammatory processes during exposure to the nerve agents
      sarin or soman [Cowan et al., 2003]. The use of various anti-inflammatory drugs
      in addition to the classical antidotal drugs (e.g. atropine and oximes) caused
      decrease in certain toxic symptoms and inflammation-induced brain damage. Our new
      bifunctional drugs (Scheme 1) are based on CNS-permeable molecular combination of
      pseudo-reversible AChE inhibitor (pyridostigmine, PYR) coupled via a hydrophobic
      spacer (octyl or decyl hydrocarbon chain) to a non-steroidal anti-inflammatory
      drug (NSAID) such as Ibuprofen or Diclofenac (Scheme 1). This study evaluates the
      efficacy of certain bifunctional compounds against HD and soman poisoning in mice
      in vivo.

PMID- 16429486
TI  - In vitro and in vivo characterization of recombinant human butyrylcholinesterase
      (Protexia) as a potential nerve agent bioscavenger.
AB  - Previous studies in rodents and nonhuman primates have demonstrated that
      pretreatment with cholinesterases can provide significant protection against
      behavioral and lethal effects of nerve agent intoxication. Human
      butyrylcholinesterase (HuBuChE) purified from plasma has been shown to protect
      against up to 5 x LD50s of nerve agents in guinea pigs and non-human primates,
      and is currently being explored as a bioscavenger pretreatment for human use. A
      recombinant form of HuBuChE has been expressed in the milk of transgenic goats as
      a product called Protexia. Protexia was supplied by Nexia Biotechnologies (Que.,
      Canada) as a purified solution with a specific activity of 600 U/mg. Initial in
      vitro studies using radiolabeled 3H-soman or 3H-DFP (diisopropyl fluorophosphate)
      demonstrated that these inhibitors specifically bind to Protexia. When Protexia
      was mixed with soman, sarin, tabun or VX using varying molar ratios of enzyme to
      nerve agent (8:1, 4:1, 1:1 and 1:4, respectively), the data indicated that 50%
      inhibition of enzyme activity occurs around the 1:1 molar ratio for each of the
      nerve agents. Protexia was further characterized for its interaction with
      pyridostigmine bromide and six unique carbamate inhibitors of cholinesterase.
      IC50 and Ki values for Protexia were determined to be very similar to those of
      HuBuChE purified from human plasma. These data suggest that Protexia has
      biochemical properties very similar to those HuBuChE when compared in vitro.
      Together these data the continued development of the goat milk-derived
      recombinant HuBuChE Protexia as a potential bioscavenger of organophosphorus
      nerve agents.

PMID- 16429487
TI  - Report on the guidelines on parenteral nutrition in infants, children and
      adolescents.

PMID- 16429488
TI  - Acetylcholinesterase and butyrylcholinesterase of freshwater teleosts.
AB  - Long period there was opinion that tissues of freshwater teleosts contain solely
      acetylcholinesterase (AChE; EC 3.1.1.7), while butyrylcholinesterase (BuChE; EC
      3.1.1.8) is present in traces. Our investigations during last two decades change
      the view.

PMID- 16429489
TI  - Comparison of the potency of newly developed and currently available oximes to
      reactivate nerve agent-inhibited acetylcholinesterase in vitro and in vivo.
AB  - Reactivation potency of three newly developed oximes K027, K033 and K048 was
      tested using standard in vitro and in vivo reactivation tests. K027 and K048 seem
      to be efficacious reactivators of tabun-inhibited acetylcholinesterase. K033 is
      sufficient reactivator of cyclosarin-inhibited AChE. However, its potency is poor
      compared with current "gold standard" oxime HI-6.

PMID- 16429490
TI  - Ex vivo anticholinesterase activity of benzoic acid derivatives.
AB  - p-Aminobenzoic acid (p-ABA) derivatives were evaluated as acetylcholinesterase
      inhibitors (AChEIs). Finding a correlation between AChE activity with the
      partition coefficient (log P) and the highest occupied molecular orbital (HOMO)
      energy of the compounds.

PMID- 16429491
TI  - A novel strategy for protection against organophosphate toxicity: Evolution of
      cyclic inhibitors with high affinity for the acetylcholinesterase peripheral
      site.

PMID- 16429495
TI  - A single mutation near the C-terminus in alpha/beta hydrolase fold protein family
      causes a defect in protein processing.
AB  - An Arg to Cys mutation in the extracellular domain of neuroligin-3 (NL3) was
      recently found in a twin set with autism [S. Jamain, H. Quach, C. Betancur, M.
      Rastam, C. Colineaux, I.C. Gillberg, H. Soderstrom, B. Giros, M. Leboyer, C.
      Gillberg, T. Bourgeron, Paris Autism Research International Sibpair Study,
      mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are
      associated with autism, Nat. Genet. 34 (2003) 27-29]. The Cys substitution in NL3
      causes altered intracellular protein trafficking, intracellular retention and
      diminished association with its cognate partner, beta-neurexin [D. Comoletti, A.
      De Jaco, L.L. Jennings, R.E. Flynn, G. Gaietta, I. Tsigelny, M.H. Ellisman, P.
      Taylor, The R451C-neuroligin-3 mutation associated with autism reveals a defect
      in protein processing, J. Neurosci. 24 (2004) 4889-4893]. NL3,
      butyrylcholinesterase (BuChE), and acetylcholinesterase (AChE), as members of the
      (/(-hydrolase fold family of proteins, share over 30% of amino acid identity in
      their extracellular domains. In particular, Arg451 in NL3 is conserved in the
      alpha/beta-hydrolase fold family being homologous to Arg386 in BuChE and Arg395
      in AChE. A Cys substitution at the homologous Arg in the BuChE was found studying
      post-succinylcholine apnea in an Australian population [T. Yen, B.N. Nightingale,
      J.C. Burns, D.R. Sullivan, P.M. Stewart, Butyrylcholinesterase (BCHE) genotyping
      for post-succinylcholine apnea in an Australian population, Clin. Chem. 49 (2003)
      1297-308]. We have made the homologous mutation in the mouse AChE and BuChE genes
      and showed that the Arg to Cys mutations resulted in identical alterations in the
      cellular phenotype for the various members of the alpha/beta-hydrolase fold
      family proteins.

PMID- 16429497
TI  - Influence of the 5' intron in the control of acetylcholinesterase gene expression
      during myogenesis.
AB  - During myogenesis, marked increases in both acetylcholinesterase (AChE) and its
      encoding mRNA are observed. The intron in the AChE gene between non-coding exon 1
      [T.L. Rachinsky, S. Camp, Y. Li, T.J. Ekstrom, M. Newton, P. Taylor, Molecular
      cloning of mouse acetylcholinesterase: tissue distribution of alternatively
      spliced mRNA species, Neuron 5 (1990) 317-327] and start-site containing exon 2
      [A. Mutero, S. Camp, P. Taylor, Promoter elements of the mouse
      acetylcholinesterase gene, J. Biol. Chem. 270 (4) (1995) 1866-1872] appears to be
      responsible for the enhanced expression of the enzyme upon myoblast to myotube
      differentiation. Deletion of a 255 bp sequence within the first intron of the
      AChE gene abolishes the increase in cell-associated activity observed with
      differentiation. To study the involvement of the intronic region in post
      transcriptional processing of AChE message, we used real time RT-PCR to quantify
      spliced and unspliced message levels in myoblasts and myotubes. We observe a 200
      fold increase of the fully spliced mRNA associated with myotube formation, while
      the increase in the unspliced mRNA retaining either intron 1 or intron 2 is only
      5 to 15-fold. We have generated knockout mice without the conserved region of
      intron 1. The mice show a phenotype where skeletal muscle, hematopoietic and
      central nervous system AChE expression differ with the greatest effect existing
      in the disappearance of skeletal muscle expression [S. Camp, L Zhang, M. Marquez,
      B. de La Torre, J.M. Long, G. Bucht, P. Taylor, Acetylcholinesterase (AChE) gene
      modification in transgenic animals: functional consequences of selected exon and
      regulatory region deletion, VIII IMC Proceedings].

PMID- 16429498
TI  - Acetylcholinesterase genes and insecticide resistance in aphids.

PMID- 16429499
TI  - Variant K of butyrylcholinesterase and types 1 and 2 of diabetes mellitus.

PMID- 16429500
TI  - The effects of indole-3-acetic acid on human and horse serum
      butyrylcholinesterase.
AB  - Butyrylcholinesterase (BChE) constitutes the first line defense in the serum of
      higher organisms and is a marker for toxic exposure. Indole-3-acetic acid (IAA)
      is a major plant growth hormone of the auxin class, affecting cell enlargement,
      and differentiation. As a result of the industrial usage, this agrochemical is
      consumed by non-target organisms. In this study, the interaction of IAA with
      purified human and horse serum BChEs were investigated. Both BChE species
      displayed biphasic hill plots using butyrylthiocholine as substrate. IAA
      interaction with BChE species was stable and concentration dependent. IAA was
      found to be linear-mixed type inhibitor for human serum BChE, and alpha and the
      Ki values were 2.15 +/- 1.09 mM and 3.09 +/- 0.95 mM, respectively. With horse
      enzyme IAA displayed uncompetitive inhibition with the Ki value of 1.05 +/- 0.09
      mM. Acquisition of large amounts of IAA is unlikely but it can be taken as a
      basis for future inhibitor designs.

PMID- 16429502
TI  - Effects of succinic acid derivatives on ex vivo acetylcholinesterase activity.
AB  - In the present study the acetylcholinesterase (AChE) inhibition and acute
      toxicity of two succinic acid derivatives were compared with tacrine.
      Administration of a single dose of each of two succinic acid derivatives produced
      a time and dose-dependent inhibition of brain AChE activity. Although the
      magnitude of the cholinergic effects observed with the two succinic acid
      derivatives was similar to that seen with tacrine and other AChE inhibitors, the
      toxicity study showed that the new inhibitors have less adverse side effects.

PMID- 16429504
TI  - Transcriptional induction of cholinesterase expression and protection against
      chemical warfare nerve agents.
AB  - We investigated whether transcriptional inducers could enhance the expression of
      acetylcholinesterase (AChE) in cell lines to achieve protection against
      organophosphate (OP) poisoning. Trichostatin A (TSA), an inhibitor of histone
      deacetylase that de-condenses chromatin and increases the binding of
      transcription factors and mRNA synthesis, induced three- to four-fold
      extracellular and 8-10-fold intracellular AChE expression at the optimal dose of
      165-333 nM in Neuro 2A cells. Pre-treatment with TSA protected against OP
      exposure. Thus, transcriptional inducers, such as TSA, up-regulate AChE, which
      then can scavenge the OP and protect the cells from OP-induced toxicity, and are
      potential novel ways to treat chemical warfare nerve agent (CWNA) exposure.

PMID- 16429505
TI  - Synthesis and structure activity relationships (SAR) of a new class of potent and
      selective butyrylcholinesterase inhibitors.
AB  - Reported here is the synthesis and SAR of novel group of highly potent and
      selective inhibitors of human plasma butyrylcholinesterase (BuChE; EC 3.1.1.8).
      The design is based on the discovery that isosorbide 2-esters are hydrolysed by
      BuChE at exceptionally rapid rates. Two families of carbamates were synthesised
      in which the vulnerable 2-ester was replaced with a carbamate or reversed
      carabamate. Several compounds in one of the families are among the most potent
      and selective BuChE inhibitors reported.

PMID- 16429510
TI  - Inhibition of guinea pig hemi-diaphragm acetylcholinesterase activity by
      pyridostigmine bromide and protection against soman toxicity.

PMID- 16429512
TI  - Identification of organophosphate-reactive proteins by tandem mass spectrometry.

PMID- 16429515
TI  - Measuring carbamoylation and decarbamoylation rate constants by continuous assay
      of AChE.

PMID- 16429518
TI  - Comparison of ability of some oximes to reactivate sarin-inhibited brain
      acetylcholinesterase from different species.
AB  - The aim of this work was the comparison of reactivation potency of four oxime
      acetylcholinesterase (AChE) reactivators (pralidoxime, HI-6, K027 and K033) on
      three resources of the enzyme (human, pig and rat brain homogenate) inhibited by
      nerve agent sarin. The results demonstrate remarkable differences in the
      reactivation of inhibited brain AChE, depending on the oxime and species

PMID- 16429521
TI  - Acetylcholinesterase effects on glutamate receptors.
AB  - We studied acetylcholinesterase (AChE) effects on glutamate receptors (GluR) in
      rat brain sections, synaptosomal membranes and cultured hippocampal neurones. A
      selective potentiation of AMPA receptors (AMPAR) binding in AMPAR-enriched layers
      undergoing synaptogenesis plus an increased surface expression of synaptic
      clusters of GluR1, GluR2, and SV2a was found. Thus, the AMPAR synaptic
      recruitment induced by AChE, could be a molecular mechanism underlying its non
      classical synaptogenic actions.

PMID- 16429526
TI  - Acetylcholinesterase mutants: oxime-assisted catalytic scavengers of
      organophosphonates.

PMID- 16429527
TI  - Attenuation of the effects of physostigmine by hyoscine in guinea-pig brain
      cholinergic enzymes: cholineacetyltransferase.

PMID- 16429528
TI  - Species-related differences in the oxime-induced reactivation of organophosphate
      inhibited acetylcholinesterases.

PMID- 16429533
TI  - A. niger protein "EstA", perhaps a new electrotactin, defines a new class of
      fungal esterases within the alpha/beta hydrolase fold superfamily.
AB  - Protein EstA from Aspergillus niger was characterized through a multifaced
      approach involving molecular biology, bioinformatics, biophysical, biochemical
      and enzymatical analyses. EstA was identified as the lead member, within the
      superfamily of proteins with an alpha/beta-hydrolase fold, of a new class of
      fungal esterases that also contains predicted homologs from other fungus species
      of known broad host-range pathogenicity.

PMID- 16429535
TI  - Structural insights into AChE inhibition by monoclonal antibodies.
AB  - The target sites of three inhibitory monoclonal antibodies, Elec403, 408 and 410,
      on eel AChE have been defined previously. Elec403 and 410 are directed toward
      distinct but overlapping epitopes at the enzyme peripheral site, while Elec408
      binds to a distinct regulatory site on the enzyme surface, where the "back door"
      may be located. Elec410 also inhibits Bunganus fasciatus AChE. To investigate the
      molecular determinants for AChE inhibition by these antibodies, we have cloned
      and sequenced the IgGs, generated, purified, characterized the Fab molecules, and
      initiated crystallographic and theoretical modeling studies. Preliminary data are
      presented.

PMID- 16429536
TI  - H2O2 modifies membrane structure and activity of acetylcholinesterase.
AB  - The main factor of Alzheimer disease (AD) is beta-amyloid peptide (Abeta). It is
      known to affect acetylcholinesterase (AChE) through lipid peroxidation (LPO)
      initiated with H2O2 which is formed as a result of Abeta activity. The direct
      action of H2O2 on the enzyme is also possible. For membrane bound AChE of
      erythrocytes we observed inhibition under H2O2 action which was replaced by
      activation at small H2O2 concentrations. At higher substrate concentrations the
      inversion of the effect came at smaller concentrations of H2O2. For soluble
      erythrocytic AChE inhibition took place (caused by Km increase). Soluble enzyme
      from Electric Eel revealed inhibition, which was not replaced by activation at
      any concentration of peroxide. Low H2O2 concentrations caused intensification of
      lipid peroxidation in microsomes. The magnitude of the changes in LPO rate was
      within the range of the changes, where LPO system fulfills the control function
      for cell metabolism. With the help of ESR technique of spin probes it was found
      the rigidization under H2O2 action of close to surface area of lipid bilayer in
      erythrocytic and brain cell membranes. Summing up we can say that H2O2 modifies
      membrane structure and activity of AChE. Whether or not it will contribute to AD
      pathogenesis or is the manifestation of compensatory processes-the possible
      subject of discussion and further investigation.

PMID- 16429545
TI  - BW284c51 blocks nicotinic acetylcholine receptors transplanted to Xenopus
      oocytes.
AB  - We have studied the effects of BW284c51 on the function of Torpedo nicotinic
      acetylcholine (Ach) receptors (nAchRs) transplanted to Xenopus laevis oocytes.
      BW284c51 reversible inhibited Ach-elicited currents (IAch) in a concentration
      dependent manner, increased IAch desensitisation and changed the Ach
      concentration-dependence of the IAch from a two-site to a single-site Hill
      equation, without affecting the EC50. These effects were only present at
      hyperpolarising potentials, suggesting that nAchR blockade by BW284c51 is non
      competitive and likely due to an open channel block as the principal mechanism.

PMID- 16429548
TI  - Characterizing pea acetylcholinesterase.
AB  - Although the best-defined role of acetylcholinesterase (AChE) is to terminate
      cholinergic transmission signals, the presence of the enzyme and its substrate is
      not limited to the metazoan nervous system. Here, we describe the presence of
      cholinesterase and its initial characterization in pea roots.

PMID- 16429549
TI  - Structural data on the aging of diethylphosphoryl-butyrylcholinesterase.

PMID- 16429555
TI  - Mouse AChE binds in vivo to domain IV of laminin-1beta.
AB  - Functions of acetylcholinesterase (AChE) other than hydrolysis of acetylcholine,
      e.g. related to cell differentiation, synaptogenesis, neuronal signaling and
      diseases are well documented, but mechanisms supporting them are not understood.
      Therefore, we searched for AChE ligands in the central nervous system using a
      yeast two-hybrid screen (Y2H). 18 independent candidates were identified. One of
      the membrane or extracellular proteins was laminin-1, an extracellular matrix
      protein involved in neuronal differentiation and adhesion. The laminin-1 fragment
      found to interact with AChE contains 898 bp from the 1beta-chain. Moreover, we
      identified the region containing amino acid residues 240-503 of AChE as essential
      for interaction with laminin-1beta. Co-immunoprecipitation experiments confirmed
      the yeast two-hybrid results.

PMID- 16429560
TI  - Ligand-induced conformational changes in residues flanking the active site gorge
      of acetylcholinesterase.

PMID- 16429564
TI  - Computational approaches to the study of dual-site and peripheral site binding
      ache inhibitors.

PMID- 16429565
TI  - Decalin-type acetylcholine-mimetic organophosphates as inhibitors of
      acetylcholinesterase.
AB  - The novel decalin-type N,O,P-heterocycles, P(3)-axially and P(3)-equatorially
      substituted cis- and trans-configurated 3-fluoro-2,4-dioxa-7-aza-, 2,4-dioxa-8
      aza-, and 2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides, are
      configuratively fixed and conformationally constrained phosphorus analogues of
      acetylcholine. The compounds are suitable probes for the investigation of
      molecular interactions with acetylcholinesterase.

PMID- 16429566
TI  - The stereochemistry of the inhibition of acetylcholinesterase with acetylcholine
      mimetic 7-aza-2,4-dioxaphosphadecalins.
AB  - The irreversible inhibition of acetylcholinesterase with the decalin-type cis-
      and trans-3-fluoro-2,4-dioxa-7-aza-3-phosphadecalins was investigated by 31P-NMR
      spectroscopy. The stereochemical outcome (inversion or retention at the P-atom)
      is dependent on the structure of the inhibitors.

PMID- 16429567
TI  - Preparation of enantiomers of quinuclidin-3-Ol derivatives and their interactions
      with human cholinesterases.

PMID- 16429568
TI  - Structure-inhibition relationships in the interaction of butyrylcholinesterase
      with bambuterol, haloxon and their leaving groups.

PMID- 16429571
TI  - ATP induces the post-synaptic gene expression in neuron-neuron synapses:
      Transcriptional regulation of AChE catalytic subunit.
AB  - Adenosine 5'-triphosphate (ATP) is an important trophic factor, which is co
      stored and co-released at central and peripheral cholinergic synapses. The
      synaptic ATP induces post-synaptic gene transcription during the formation and
      maintenance of vertebrate neuromuscular junction (nmj) via a mitogen-activaton
      protein (MAP) kinase signaling pathway and subsequently activates
      acetylcholinesterase (AChE) and acetylcholine receptor (AChR) genes. However, the
      role of ATP in the central nervous system is still not clear. Primary culture of
      rat cortical neurons was used as a model system to study the biological functions
      of ATP in neuron-neuron synapses. During the differentiation of cultured cortical
      neurons, the protein levels of AChE and one of the ATP receptor subtypes, P2Y1
      receptor, were increased. By using a human AChE promoter tagged with a luciferase
      reporter gene, the transcriptional regulation of AChE gene by ATP could be
      monitored. The activation of P2Y1 receptors could regulate the AChE promoter
      activity in cultured cortical neurons. These results suggested the activation of
      P2Y receptors may play role(s) in synaptic gene expression of neuron-neuron
      synapses in the brain.

PMID- 16429574
TI  - An ex vivo approach for the evaluation of reversible inhibitors as potential
      pretreatments against organophosphate toxicity.
AB  - Several studies demonstrated that pretreatment with reversible
      acetylcholinesterase (AChE) inhibitor, such as (pyridostigmine) PYR, improved the
      survival of animals intoxicated by organophosphate nerve agents (OP). These
      compounds temporarily inhibited a fraction of the enzyme and protected it from
      inactivation by nerve agents. An important criterion for effective pretreatment
      is that it must ensure the recovery of the protected fraction of the enzyme. We
      thus designed a simple ex vivo method to investigate the recovery of AChE
      activity, that was protected by PYR, prior to irreversible inhibition by an OP,
      using a modified Ellman assay. Results show that our approach is suitable for
      routine use and can successfully predict the potential use of various AChE
      inhibitors as pretreatment drugs against OP nerve agent intoxication.

PMID- 16429577
TI  - Safety and pharmacokinetics of human serum butyrylcholinesterase in guinea pigs.
AB  - Human serum butyrylcholinesterase (Hu BChE) has been demonstrated to be a highly
      effective detoxifying enzyme for counteracting the acute toxicity of
      organophosphorus (OP) nerve agents. In order to initiate an investigational new
      drug (IND) application for human use, the safety and pharmacokinetic properties
      of the enzyme were assessed in guinea pigs. Sixty milligrams per kilogram of Hu
      BChE was administered to guinea pigs by either i.p. or i.m. injection. Blood was
      drawn at various time points for up to 2 weeks following enzyme injection for the
      measurement of blood BChE activity. Hu BChE displayed a mean residence time of
      110 h, regardless of the route of administration and the enzyme activity remained
      almost 10-fold above baseline level even after 2 weeks post enzyme injection.
      Fourteen days post Hu BChE administration, all animals were subjected to 20 panel
      serum chemistry, hematology, and complete gross/histopathology examination.
      Results showed no toxic effects as measured by general observation, serum
      chemistry, hematology, and gross and histological tissue changes. In conclusion,
      Hu BChE displays a long-lasting stability in the circulation of guinea pigs, and
      is devoid of any toxic side effects. These results provide convincing data for
      the safe and effective use of Hu BChE as a bioscavenger to protect humans against
      all OP nerve agents.

PMID- 16429578
TI  - Cholinesterase activity and enzyme components in healthy and cancerous human
      colorectal sections.
AB  - The effect of cancer on acetyl- (AChE) and butyrylcholinesterase (BuChE)
      activities of human gut was investigated. ChE activity was measured in 55 paired
      samples of healthy and malignant colon, sigmoid colon and rectum. Cancer
      decreases the mean AChE activity value from 2.17 +/- 1.07 to 1.40 +/- 0.89 mU/mg
      (p < 0.001), and BuChE activity from 4.16 +/- 2.41 to 1.65 +/- 0.87 mU/mg (p <
      0.001). AChE monomers and dimers (light forms), and less asymmetric and
      tetrameric variants (heavy forms) were identified in gut. The proportions of the
      heavy species dropped in malignant colon. Since muscarinic stimulation is needed
      for human colon cancer cell proliferation, the fall of ChE activity in neoplastic
      colon, with the increased availability of acetylcholine, may increase tumour
      growth.

PMID- 16429580
TI  - Muscular dystrophy with laminin deficiency decreases acetylcholinesterase
      activity in thymus of dystrophic Lama2dy mice.
AB  - We have studied the effect of muscular dystrophy by merosin deficiency on mouse
      thymus acetyl- (AChE) and butyrylcholinesterase (BuChE). The organ contains AChE
      and BuChE activities. Merosin deficiency causes an important decrease (46%) in
      AChE specific activity. Thymus produces dimers, monomers and tetramers of AChE,
      and the three kinds of AChE mRNAs. The drop in AChE activity in dystrophic
      animals could affect the amount of ACh reaching cholinergic receptors in cells of
      lymphoid organs.

PMID- 16429581
TI  - Regulation of PRiMA: membrane anchor of acetylcholinesterase (AChE) in neuron and
      muscle.

PMID- 16429582
TI  - Steric effects in the decarbamoylation of carbamoylated acetylcholinesterases.

PMID- 16429583
TI  - Gerontologic nurse practitioner care guidelines: oral health of older adults:
      problems and management.

PMID- 16429584
TI  - A midwifery degree: an endurance test?

PMID- 16429585
TI  - Significant exposure to tobacco smoke and underuse of controller medications
      exacerbate asthma symptoms among Head Start children.

PMID- 16429586
TI  - Imaging D2-receptors in quinolinic acid lesioned rat striatum with high
      resolution pinhole SPECT.

PMID- 16429587
TI  - Intestinal malrotation and delayed gastric emptying.

PMID- 16429589
TI  - Quantitative analyses of Streptococcus mutans biofilms with quartz crystal
      microbalance, microjet impingement and confocal microscopy.
AB  - Microbial biofilm formation can be influenced by many physiological and genetic
      factors. The conventional microtiter plate assay provides useful but limited
      information about biofilm formation. With the fast expansion of the biofilm
      research field, there are urgent needs for more informative techniques to
      quantify the major parameters of a biofilm, such as adhesive strength and total
      biomass. It would be even more ideal if these measurements could be conducted in
      a real-time, non-invasive manner. In this study, we used quartz crystal
      microbalance (QCM) and microjet impingement (MJI) to measure total biomass and
      adhesive strength, respectively, of S. mutans biofilms formed under different
      sucrose concentrations. In conjunction with confocal laser scanning microscopy
      (CLSM) and the COMSTAT software, we show that sucrose concentration affects the
      biofilm strength, total biomass, and architecture in both qualitative and
      quantitative manners. Our data correlate well with previous observations about
      the effect of sucrose on the adherence of S. mutans to the tooth surface, and
      demonstrate that QCM is a useful tool for studying the kinetics of biofilm
      formation in real time and that MJI is a sensitive, easy-to-use device to measure
      the adhesive strength of a biofilm.

PMID- 16429590
TI  - Shifting the Measuring Range of Chloride Selective Electrodes and Optodes Based
      on the Anticrown Ionophore [9]Mercuracarborand-3 by the Addition of 1
      Decanethiol.
AB  - Ion-selective electrodes and optodes based on the anticrown ionophore
      mercuracarborand-3 (MC-3) exhibit excellent selectivity to halide ions but suffer
      from a low upper detection limit because of very strong complexation in the
      sensing phase. In this work, we have successfully improved the upper detection
      limit and widened the working range of chloride selective electrode based on MC-3
      by introducing 1-decanethiol into the membrane cocktail. With an assumed 1:2
      stoichiometry between chloride and MC-3 the apparent complex formation constant
      was reduced from log beta = 13.4 as reported for the membrane without the
      addition of 1-decanethiol to log beta = 12.13, log beta = 10.84 and log beta =
      5.67 with the addition of a 1:1, 1:2 and 1:4 molar ratio of 1-decanethiol to MC
      3. Besides these values, obtained with the sandwich membrane method, similar
      shifts in the measuring range of thin optode film responses to lower chloride
      concentrations were observed as well. The selectivity of the modified membrane
      was found to be very good, with hydroxide and the other halides: bromide and
      iodide, as the main interferences. Based on these results, corresponding iodide
      selective electrodes were prepared that showed a near-Nernstian iodide slope,
      rather than a cationic slope as observed without thiol additive.Jonoselektywne
      elektrody i optody stosujace antykoronowy jonofor [9]merkuracarborand-3 (MC-3)
      charakteryzuja sie doskonala selektywnoscia w stosunku do jonow halogenkow lecz
      wskutek silnego kompleksowania w fazie receptora maja ograniczony zakres gornej
      granicy oznaczalnosci. W przedstawionej pracy poszerzono zakres stosowalnosci
      dzieki wprowadzeniu 1-dekanotiolu do membrany zawierajacej MC-3. Przy zalozonej
      stechiometrii kompleksu chlorek-MC-3 rownej 1:2 stala tworzenia kompleksu zostala
      obnizona, z wartosci log beta = 13,4 (w przypadku membrany bez dodatku 1
      dekanotiolu) do wartosci log beta = 12,13; log beta = 10,84 i log beta = 5,67 (po
      dodaniu 1-dekanotiolu) dla stosunkow molowych stezen-1-dekanotiol:MC-3
      wynoszacych odpowiednio 1:1, 1:2 i 1:4. Ponadto oprocz tych danych otrzymanych
      metoda warstwowej membrany, podobne przesuniecie zakresu pomiarowego obserwowano
      w przypadku malych stezen chlorkow dla cienkowarstwowej optody. Selektywnos c
      modyfikowanej membrany byla dobra, przy czym glownymi interferentami byly jony
      bromkowe, jodkowe i wodorotlenkowe. W oparciu o te wyniki skonstruowano elektrode
      czula na jony jodkowe, charakteryzujaca sie nachyleniem anionowym charakterystyki
      bliskim Nernstowskiemu, a nie kationowym wykazywanym w nieobecnosci tiolu.

PMID- 16429591
TI  - Clinical screening of school children for polysomnography to detect sleep
      disordered breathing--the Tucson Children's Assessment of Sleep Apnea study
      (TuCASA).
AB  - STUDY OBJECTIVES: This report describes the associations, specificities,
      sensitivities, and positive likelihood ratios of clinical symptoms to a finding
      of sleep-disordered breathing (SDB) on polysomnography in children. METHODS: Four
      hundred eighty unattended home polysomnograms were completed in a community-based
      cohort of children 6 to 11 years of age (50% boys, 42.3% Hispanic, and 52.9%
      between the ages of 6 and 8 years). SDB was present if the child had a
      respiratory disturbance index of > or = 1 event per hour. MEASUREMENTS AND
      RESULTS: Boys were twice as likely as girls to have SDB (p < .01); however,
      witnessed apnea, ethnicity, age, obesity, and airway size (based on clinical
      evaluation) were not significantly different between those with SDB and without
      SDB. The sensitivity of any individual or combined clinical symptoms was poor,
      with male sex (60%) and snoring (29.5%) having the greatest proportion of SDB
      children. However, high specificities for snoring (89.5%), excessive daytime
      sleepiness (86.3%), and learning problems (95.9%) were noted. Combinations of
      symptoms such as snoring+male sex (95.1%), snoring+excessive daytime sleepiness
      (97.0%), and snoring+learning problems (98.9%) had specificities approaching 1.
      Positive likelihood ratios for snoring (2.8), learning (2.8), and symptoms
      combined with snoring such as snoring+male sex (3.9), snoring+learning problems
      (4.0), and snoring+excessive daytime sleepiness (2.9) were observed. CONCLUSIONS:
      Snoring, excessive daytime sleepiness, and learning problems are each highly
      specific, but not sensitive, for SDB in 6- to 11-year old children. However,
      specificities and positive likelihood ratios for the combination of some of these
      symptoms is sufficiently high to suggest that some children may not require a
      polysomnogram for the diagnosis of SDB.

PMID- 16429592
TI  - Social Support, Traumatic Events, and Depressive Symptoms Among African
      Americans.
AB  - Structural equation modeling was used to examine the relationships among stress,
      social support, negative interaction, and mental health in a sample of African
      American men and women between ages 18 and 54 (N = 591) from the National
      Comorbidity Study. The study findings indicated that social support decreased the
      number of depressive symptoms, did not mitigate the effects of stress, and was
      reduced in response to financial strain. Financial strain and traumatic events
      were associated with increased negative interaction with relatives and depressive
      symptoms. The findings verify that stressful and traumatic events have direct
      influences on levels of depressive symptoms and affect the quality of social
      interactions and suggest how social interaction processes contribute to mental
      health.

PMID- 16429593
TI  - Enhancing the photoluminescence of peptide-coated nanocrystals with shell
      composition and UV irradiation.
AB  - The composition and structure of inorganic shells grown over CdSe semiconductor
      nanocrystal dots and rods were optimized to yield enhanced photoluminescence
      properties after ligand exchange followed by coating with phytochelatin-related
      peptides. We show that, in addition to the peptides imparting superior colloidal
      properties and providing biofunctionality in a single-step reaction, the improved
      shells and pretreatment with UV irradiation resulted in high quantum yields for
      the nanocrystals in water. Moreover, peptide coating caused a noticeable red
      shift in the absorption and emission spectra for one of the tested shells,
      suggesting that exciton-molecular orbital (X-MO) coupling might take place in
      these hybrid inorganic-organic composite materials.

PMID- 16429594
TI  - Fluorocarbon Surfactant Polymers: Effect of Perfluorocarbon Branch Density on
      Surface Active Properties.
AB  - We describe a series of fluorocarbon surfactant polymers designed for modifying
      fluorocarbon surfaces such as poly(tetrafluoroethylene). Novel fluorocarbon
      surfactant polymers poly(N-vinyldextranaldonamide-co-N
      vinylperfluoroundecanamide), in which hydrophilic dextran oligosaccharides and
      hydrophobic perfluoroundecanoyl groups were incorporated sequentially onto a
      poly(vinylamine) backbone, were synthesized and characterized by FT-IR, NMR, and
      XPS spectroscopy. By adjusting the feed ratio of dextran to fluorocarbon
      branches, surfactant polymers with different hydrophilic/hydrophobic balances
      were prepared. The surface activity of the surfactants at the air/water interface
      was demonstrated by significant reductions in water surface tension. Surfactant
      adsorption and adhesion at the solid PTFE/aqueous interface were examined under
      well-defined dynamic flow conditions, using a rotating disk system. The surface
      activity at the air/water interface and adhesion stability on PTFE under an
      applied shear stress both increase with increasing density of fluorocarbon
      branches on the polymer backbone. The results show that stable surfactant
      adhesion on PTFE can be achieved by adjusting the hydrophilic dextran to
      hydrophobic fluorocarbon branch ratio.

PMID- 16429595
TI  - Commercial Seed Lots Exhibit Reduced Seed Dormancy in Comparison to Wild Seed
      Lots of Echinacea purpurea.
AB  - Seed germination patterns were studied in E. purpurea (L.) Moench grouped by seed
      source, one group of seven lots from commercially cultivated populations and a
      second group of nine lots regenerated from ex situ conserved wild populations.
      Germination tests were conducted in a growth chamber in light (40 MUmol.m(-2).s(
      1)) or darkness at 25  degrees C for 20 days after soaking the seeds in water for
      10 minutes. Except for two seed lots from wild populations, better germination
      was observed for commercially cultivated populations in light (90% mean among
      seed lots, ranging from 82% to 95%) and in darkness (88% mean among seed lots,
      ranging from 82% to 97%) than for wild populations in light (56% mean among seed
      lots, ranging from 9% to 92%) or in darkness (37% mean among seed lots, ranging
      from 4% to 78%). No germination difference was measured between treatments in
      light and darkness in the commercially cultivated populations, but significant
      differences were noted for treatments among wild populations. These results
      suggest that repeated cycles of sowing seeds during cultivation without
      treatments for dormancy release resulted in reduced seed dormancy in E. purpurea.

PMID- 16429596
TI  - Chromosome Karyotypes of Echinacea angustifolia var. angustifolia and E.
      purpurea.
AB  - Chromosome karyotypes of the most commonly cultivated and medicinally used
      Echinacea taxa, E. angustifolia DC. var. angustifolia and E. purpurea (L.)
      Moench., were analyzed. The chromosomes of both taxa are medium in length,
      ranging from 4.12 to 5.83 MUm in E. angustifolia var. angustifolia and 3.99 to
      6.08 MUm in E. purpurea. No abrupt length changes in the chromosomes were noted.
      The karyotypes of the two species are generally similar, but a distinguishable
      feature exists in one pair of chromosomes. The centromere of chromosome pair 10
      is subterminally located in E. purpurea, but terminally located in E.
      angustifolia var. angustifolia, which can be readily recognized in mitotic
      metaphase cell plates. This finding may provide useful information for Echinacea
      evolutionary, genetic, and breeding studies.

PMID- 16429598
TI  - Patterns of Variation in Alkamides and Cichoric Acid in Roots and Aboveground
      Parts of Echinacea purpurea (L.) Moench.
AB  - We investigated patterns of variation in alkamides and cichoric acid accumulation
      in the roots and aboveground parts of Echinacea purpurea (L.) Moench. These
      phytochemicals were extracted from fresh plant parts with 60% ethanol and
      quantified by high performance liquid chromatography (HPLC) analysis.
      Concentrations of alkamides and cichoric acid were measured on a dry-weight basis
      (mg.g(-1)). For total alkamides, concentrations among individual plants varied
      from 5.02 to 27.67 (mean = 14.4%) in roots, from 0.62 to 3.42 (mean = 1.54) in
      nearly matured seed heads (NMSH), and 0.22 to 5.25 (mean = 0.77) in young tops
      (about 1/2 flower heads, 1/4 leaves, and 1/4 stems). For cichoric acid,
      concentrations among individual plants varied from 2.65 to 37.52 (mean = 8.95),
      from 2.03 to 31.58 (mean = 10.9), and from 4.79 to 38.55 (mean = 18.88) in the
      roots, the NMSH, and the tops, respectively. Dodeca-2E, 4E, 8Z, 10E-tetraenoic
      acid isobutylamide and dodeca-2E, 4E, 8Z, 10Z-tetraenoic acid isobutylamide
      (alkamides 8/9) accounted for only 9.4% of the total alkamides in roots, but
      comprised 87.9% in the NMSH, and 76.6% in the young tops. Correlations of
      concentrations of alkamides or cichoric acid between those of roots and those of
      the NMSH were not statistically significant, and either within the roots, the
      NMSH, and the young tops. However, a significant negative correlation was
      observed between the concentration of cichoric acid in the roots and in young
      tops, and a significant positive correlation was observed between total alkamide
      concentration in the roots and cichoric acid concentration in the young tops.
      These results may be useful in the genetic improvement of E. purpurea for
      medicinal use.

PMID- 16429599
TI  - Development and validation of the multidimensional health profile, part I:
      Psychosocial functioning.
AB  - This article describes the development and preliminary validation of the
      Multidimensional Health Profile, Part I: Psychosocial Functioning (MHP-P), a self
      report screening instrument for use in mental health and primary care settings.
      The MHP-P assesses mental health, life stress, coping skills, and social
      resources. In Study 1, retest reliability, validity, social desirability response
      bias, and factor structure were examined in a national sample of men and women (N
      = 673). In Study 2, the effect of time frame on the retest reliability of the
      mental health scales was examined in a sample of male and female college students
      (N = 147). A national sample of men and women (N = 2,411) provided data for
      additional confirmatory factor analyses and norm development in Study 3.

PMID- 16429600
TI  - Readout of the Optical PET (OPET) Detector.
AB  - The design of an imaging system capable of detecting both high-energy gamma-rays
      and optical wavelength photons is underway at the Crump Institute for Molecular
      Imaging. This system will noninvasively image small animal models in vivo for the
      presence of positron emission tomographic (PET) and optical signals. The detector
      will consist of modules of multichannel photomultiplier tubes (MC-PMT) coupled to
      arrays of scintillator crystals. The MC-PMT will detect both the photons produced
      due to bioluminescence and the photons generated by the interaction of gamma-rays
      within the crystals. The long wavelength photons produced through bioluminescence
      are only slightly attenuated by these crystals and are detected directly at the
      photocathode of the MC-PMT, resulting in signals of small (5-10 mV) short (~15
      ns) pulses. In contrast, annihilation (511 keV) gamma-rays interacting in the
      scintillator crystal send large bursts of photons to the PMT, and result in
      pulses that can be as large as 500 mV and > 200 ns duration. The processing of
      pulses with such different characteristics in a single circuit requires
      significant alteration of the standard pulse processing circuitry used in PET
      scanners. In this paper, we discuss the requirements of such a circuit and show
      the results of implementation of one design using single and multiple channel
      PMTs.

PMID- 16429601
TI  - Detector Concept for OPET-A Combined PET and Optical Imaging System.
AB  - The design of an imaging system capable of detecting both high-energy gamma-rays
      and optical wavelength photons is underway at the UCLA Crump Institute for
      Molecular Imaging. This system, which we call optical PET (OPET), will be capable
      of non-invasively and repeatedly imaging small animal models in vivo for the
      presence of PET and optical signals. In this study, we describe the physical
      principles behind the operation of the OPET imaging system and discuss the design
      concept for one of the detector modules. Additionally, we demonstrate the
      operation of an initial prototype detector module for simultaneous detection and
      imaging of annihilation radiation and single optical photons emanating from
      separate sources. These results indicate that the construction of an imaging
      system based on this detector technology is feasible.

PMID- 16429602
TI  - Gender/Racial Differences in Jock Identity, Dating, and Adolescent Sexual Risk.
AB  - Despite recent declines in overall sexual activity, sexual risk-taking remains a
      substantial danger to US youth. Existing research points to athletic
      participation as a promising venue for reducing these risks. Linear regressions
      and multiple analyses of covariance were performed on a longitudinal sample of
      nearly 600 Western New York adolescents in order to examine gender- and race
      specific relationships between "jock" identity and adolescent sexual risk-taking,
      including age of sexual onset, past-year and lifetime frequency of sexual
      intercourse, and number of sexual partners. After controlling for age, race,
      socioeconomic status, and family cohesion, male jocks reported more frequent
      dating than nonjocks but female jocks did not. For both genders, athletic
      activity was associated with lower levels of sexual risk-taking; however, jock
      identity was associated with higher levels of sexual risk-taking, particularly
      among African American adolescents. Future research should distinguish between
      subjective and objective dimensions of athletic involvement as factors in
      adolescent sexual risk.

PMID- 16429604
TI  - Investigation of OPET Performance Using GATE, a Geant4-Based Simulation Software.
AB  - A combined optical positron emission tomography (OPET) system is capable of both
      optical and PET imaging in the same setting, and it can provide
      information/interpretation not possible in single-mode imaging. The scintillator
      array here serves the dual function of coupling the optical signal from
      bioluminescence/fluorescence to the photodetector and also of channeling optical
      scintillations from the gamma rays. We report simulation results of the PET part
      of OPET using GATE, a Geant4 simulation package. The purpose of this
      investigation is the definition of the geometric parameters of the OPET
      tomograph. OPET is composed of six detector blocks arranged in a hexagonal ring
      shaped pattern with an inner radius of 15.6 mm. Each detector consists of a two
      dimensional array of 8 * 8 scintillator crystals each measuring 2 * 2 * 10 mm(3).
      Monte Carlo simulations were performed using the GATE software to measure
      absolute sensitivity, depth of interaction, and spatial resolution for two ring
      configurations, with and without gantry rotations, two crystal materials, and
      several crystal lengths. Images were reconstructed with filtered backprojection
      after angular interleaving and transverse one-dimensional interpolation of the
      sinogram. We report absolute sensitivities nearly seven times that of the
      prototype microPET at the center of field of view and 2.0 mm tangential and 2.3
      mm radial resolutions with gantry rotations up to an 8.0 mm radial offset. These
      performance parameters indicate that the imaging spatial resolution and
      sensitivity of the OPET system will be suitable for high-resolution and high
      sensitivity small-animal PET imaging.

PMID- 16429605
TI  - Relationships Between Future Orientation, Impulsive Sensation Seeking, and Risk
      Behavior Among Adjudicated Adolescents.
AB  - Because of high levels of risk behavior, adjudicated adolescents are at high risk
      for negative health outcomes such as nicotine and drug addiction and sexually
      transmitted diseases. The goal of this article is to examine relationships
      between future orientation and impulsive-sensation-seeking personality constructs
      to risk behaviors among 300 adjudicated adolescents. Significant relationships
      between impulsive sensation seeking and future orientation were found for several
      risk behaviors. Individuals with more positive future orientation were less
      likely to use marijuana, hard drugs, alcohol during sex, had fewer alcohol
      problems, had lower levels of alcohol frequency and quantity of use, and
      perceived greater risks associated with such behaviors. Higher impulsivity
      reliably predicted alcohol problems, alcohol use, condom use, and cigarette
      smoking.

PMID- 16429606
TI  - A Model of Feeding Readiness for Preterm Infants.
AB  - This paper presents a theoretical model of bottle feeding readiness in preterm
      infants, which hypothesizes relationships between bottle feeding readiness,
      experience, and outcomes. The synactive theory of development provided the
      conceptual foundation for the model. The model, which is currently being tested,
      is designed to establish bottle feeding readiness criteria that will help nurses
      decide when to offer a bottle to a preterm infant The model may also provide a
      useful framework for determining preterm infant readiness for other aspects of
      care.

PMID- 16429607
TI  - Electron Spin Relaxation Rates for High-Spin Fe(III) in Iron Transferrin
      Carbonate and Iron Transferrin Oxalate.
AB  - To optimize simulations of CW EPR spectra for high-spin Fe(III) with zero-field
      splitting comparable to the EPR quantum, information is needed on the factors
      that contribute to the line shapes and line widths. Continuous wave electron
      paramagnetic resonance (EPR) spectra obtained for iron transferrin carbonate from
      4 to 150 K and for iron transferrin oxalate from 4 to 100 K did not exhibit
      significant temperature dependence of the line shape, which suggested that the
      line shapes were not relaxation determined. To obtain direct information
      concerning the electron spin relaxation rates, electron spin echo and inversion
      recovery EPR were used to measure T(1) and T(m) for the high-spin Fe(III) in iron
      transferrin carbonate and iron transferrin oxalate between 5 and 20-30 K. For
      comparison with the data for the transferrin complexes, relaxation times were
      obtained for tris(oxalato)ferrate(III). The relaxation rates are similar for the
      three complexes and do not exhibit a strong dependence on position in the
      spectrum. Extrapolation of the observed temperature dependence of the relaxation
      rates to higher temperatures gives values consistent with the conclusion that the
      CW line shapes are not relaxation determined up to 150 K.

PMID- 16429608
TI  - Nuclear morphology measurements using Fourier domain low coherence
      interferometry.
AB  - We present a new common path configuration Fourier domain low coherence
      interferometry (fLCI) optical system and demonstrate its capabilities by
      presenting results which determine the size of cell nuclei in a monolayer of T84
      epithelial cells. The optical system uses a white light source in a modified
      Michelson interferometer and a spectrograph for detection of the mixed signal and
      reference fields. Depth resolution is obtained from the Fourier transform of the
      measured spectrum which provides the axial spatial cross-correlation between the
      signal and reference fields. The spectral dependence of scattering by the samples
      is determined by windowing the spectrum to measure the scattering amplitude as a
      function of wavenumber. We present evidence that fLCI accurately measures the
      longitudinal profile of cell nuclei rather than the transverse profile.

PMID- 16429609
TI  - The Assessment of Adult Health Care Orientations: Development and Preliminary
      Validation of the Multidimensional Health Profile-Health Functioning Index (MHP
      H) in a National Sample.
AB  - This paper describes the development and preliminary validation of the
      Multidimensional Health Profile-Health Functioning Index (MHP-H), a 69-item self
      report instrument designed to assess a variety of behaviors, perceptions,
      attitudes, and beliefs presumed to influence health status and the pursuit of lay
      and professional health care. The MHP-H briefly measures adult health history,
      health habits, health care utilization, health beliefs and attitudes, and
      response to illness (help-seeking behaviors). A national sample of adults (N =
      673) was assessed, comprising 3 age groupings (18-32, 33-50, and 51-89) crossed
      with gender and then further subdivided into several subsamples for purposes of
      reliability and validity assessment. In addition, a group of spouse "key
      informants" was also recruited. Preliminary validation of single-item indicators
      as well as confirmatory factor analyses of multi-item scales was achieved. The
      present findings support the psychometric and practical utility of the MHP-H and
      warrant its use by health psychologists in a variety of research and applied
      settings.

PMID- 16429610
TI  - Exploring surfaces and cavities in lipoxygenase and other proteins by
      hyperpolarized xenon-129 NMR.
AB  - This paper presents an exploratory study of the binding interactions of xenon
      with the surface of several different proteins in the solution and solid states
      using both conventional and hyperpolarized (129)Xe NMR. The generation of
      hyperpolarized (129)Xe by spin exchange optical pumping affords an enhancement by
      3-4 orders of magnitude of its NMR signal. As a result, it is possible to observe
      Xe directly bound to the surface of micromolar quantities of lyophilized protein.
      The highly sensitive nature of the (129)Xe line shape and chemical shift are used
      as indicators for the conditions most likely to yield maximal dipolar contact
      between (129)Xe nuclei and nuclear spins situated on the protein. This is an
      intermediate step toward achieving the ultimate goal of NMR enhancement of the
      binding-site nuclei by polarization transfer from hyperpolarized (129)Xe. The
      hyperpolarized (129)Xe spectra resulting from exposure of four different proteins
      in the lyophilized, powdered form have been examined for evidence of binding.
      Each of the proteins, namely, metmyoglobin, methemoglobin, hen egg white
      lysozyme, and soybean lipoxygenase, yielded a distinctly different NMR line
      shape. With the exception of lysozyme, the proteins all possess a paramagnetic
      iron center which can be expected to rapidly relax the (129)Xe and produce a net
      shift in its resonance position if the noble gas atom occupies specific binding
      sites near the iron. At temperatures from 223 to 183 K, NMR signals were observed
      in the 0-40 ppm chemical shift range, relative to Xe in the gas phase. The
      signals broadened and shifted downfield as the temperature was reduced,
      indicating that Xe is exchanging between the gas phase and internal or external
      binding sites of the proteins. Additionally, conventional (129)Xe NMR studies of
      metmyoglobin and lipoxygenase in the solution state are presented. The
      temperature dependence of the chemical shift and line shape indicate exchange of
      Xe between adsorption sites on lipoxygenase and Xe in the solvent on the slow to
      intermediate exchange time scale. The NMR results are compared with N(2), Xe, and
      CH(4) gas adsorption isotherms. It is found that lipoxygenase is unique among the
      proteins studied in possessing a relatively high affinity for gas molecules, and
      in addition, demonstrating the most clearly resolved adsorbed (129)Xe NMR peak in
      the lyophilized state.

PMID- 16429611
TI  - Methods for haptic feedback in teleoperated robot-assisted surgery.
AB  - Teleoperated minimally invasive surgical robots can significantly enhance a
      surgeon's accuracy, dexterity and visualization. However, current commercially
      available systems do not include significant haptic (force and tactile) feedback
      to the operator. This paper describes experiments to characterize this problem,
      as well as several methods to provide haptic feedback in order to improve
      surgeon's performance. There exist a variety of sensing and control methods that
      enable haptic feedback, although a number of practical considerations, e.g. cost,
      complexity and biocompatibility, present significant challenges. The ability of
      teleoperated robot-assisted surgical systems to measure and display haptic
      information leads to a number of additional exciting clinical and scientific
      opportunities, such as active operator assistance through "virtual fixtures" and
      the automatic acquisition of tissue properties.

PMID- 16429612
TI  - Hydration energies and structures of alkaline earth metal ions, M2+(H2O)n, n = 5
      7, M = Mg, Ca, Sr, and Ba.
AB  - The evaporation of water from hydrated alkaline earth metal ions, produced by
      electrospray ionization, was studied in a Fourier transform mass spectrometer.
      Zero-pressure-limit dissociation rate constants for loss of a single water
      molecule from the hydrated divalent metal ions, M(2+)(H(2)O)(n) (M = Mg, Ca, and
      Sr for n = 5-7, and M = Ba for n = 4-7), are measured as a function of
      temperature using blackbody infrared radiative dissociation. From these values,
      zero-pressure-limit Arrhenius parameters are obtained. By modeling the
      dissociation kinetics using a master equation formalism, threshold dissociation
      energies (E(o)) are determined. These reactions should have a negligible reverse
      activation barrier; therefore, E(o) values should be approximately equal to the
      binding energy or hydration enthalpy at 0 K. For the hepta- and hexahydrated ions
      at low temperature, binding energies follow the trend expected on the basis of
      ionic radii: Mg > Ca > Sr > Ba. For the hexahydrated ions at high temperature,
      binding energies follow the order Ca > Mg > Sr > Ba. The same order is observed
      for the pentahydrated ions. Collisional dissociation experiments on the
      tetrahydrated species result in relative dissociation rates that directly
      correlate with the size of the metals. These results indicate the presence of two
      isomers for hexahydrated magnesium ions: a low-temperature isomer in which the
      six water molecules are located in the first solvation shell, and a high
      temperature isomer with the most likely structure corresponding to four water
      molecules in the inner shell and two water molecules in the second shell. These
      results also indicate that the pentahydrated magnesium ions have a structure with
      four water molecules in the first solvation shell and one in the outer shell. The
      dissociation kinetics for the hexa- and pentahydrated clusters of Ca(2+), Sr(2+),
      and Ba(2+) are consistent with structures in which all the water molecules are
      located in the first solvation shell.

PMID- 16429613
TI  - Binding energies of hexahydrated alkaline earth metal ions, M2+(H2O)6, M = Mg,
      Ca, Sr, Ba: evidence of isomeric structures for magnesium.

PMID- 16429615
TI  - Transcriptional profiling in an MPNST-derived cell line and normal human Schwann
      cells.
AB  - cDNA microarrays were utilized to identify abnormally expressed genes in a
      malignant peripheral nerve sheath tumor (MPNST)-derived cell line, T265, by
      comparing the mRNA abundance profiles with that of normal human Schwann cells
      (nhSCs). The findings characterize the molecular phenotype of this important cell
      line model of MPNSTs, and elucidate the contribution of Schwann cells in MPNSTs.
      In total, 4608 cDNA sequences were screened and hybridizations replicated on
      custom cDNA microarrays. In order to verify the microarray data, a large
      selection of differentially expressed mRNA transcripts were subjected to semi
      quantitative reverse transcription PCR (LightCycler). Western blotting was
      performed to investigate a selection of genes and signal transduction pathways,
      as a further validation of the microarray data. The data generated from multiple
      microarray screens, semi-quantitative RT-PCR and Western blotting are in broad
      agreement. This study represents a comprehensive gene-expression analysis of an
      MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs
      in culture. This study has identified ~900 genes that are expressed abnormally in
      the T265 cell line and detected many genes not previously reported to be
      expressed in nhSCs. The results provide crucial information on the T265 cells
      that is essential for investigation using this cell line in experimental studies
      in neurofibromatosis type I (NF1), and important information on normal human
      Schwann cells that is applicable to a wide range of studies on Schwann cells in
      cell culture.

PMID- 16429616
TI  - Adenosine: an activity-dependent axonal signal regulating MAP kinase and
      proliferation in developing Schwann cells.
AB  - Nonsynaptic release of ATP from electrically stimulated dorsal root gangion (DRG)
      axons inhibits Schwann cell (SC) proliferation and arrests SC development at the
      premyelinating stage, but the specific types of purinergic receptor(s) and
      intracellular signaling pathways involved in this form of neuron-glia
      communication are not known. Recent research shows that adenosine is a neuron
      glial transmitter between axons and myelinating glia of the CNS. The present
      study investigates the possibility that adenosine might have a similar function
      in communicating between axons and premyelinating SCs. Using a combination of
      pharmacological and molecular approaches, we found that mouse SCs in culture
      express functional adenosine receptors and ATP receptors, a far more complex
      array of purinergic receptors than thought previously. Adenosine, but not ATP,
      activates ERK/MAPK through stimulation of cAMP-linked A2(A) adenosine receptors.
      Both ATP and adenosine inhibit proliferation of SCs induced by platelet-derived
      growth factor (PDGF), via mechanisms that are partly independent. In contrast to
      ATP, adenosine failed to inhibit the differentiation of SCs to the O4+ stage.
      This indicates that, in addition to ATP, adenosine is an activity-dependent
      signaling molecule between axons and premyelinating Schwann cells, but that
      electrical activity, acting through adenosine, has opposite effects on the
      differentiation of myelinating glia in the PNS and CNS.

PMID- 16429617
TI  - [Current status of 18F-FDG PET in predicting outcome of cancer therapy].

PMID- 16429618
TI  - A historical perspective of the New Zealand asthma mortality epidemics.

PMID- 16429619
TI  - A double-blind randomized placebo control study comparing the  objective and
      subjective changes in female sexual response using sublingual apomorphine.
AB  - INTRODUCTION: Female sexual dysfunction and its therapeutic approach is a growing
      area. AIM: We aimed to assess the subjective and objective changes of the female
      sexual response, in patients with orgasmic sexual dysfunction using 3 mg SL
      Apomorphine (APO). METHODS: Twenty-four patients (mean age 32 years old, SD:
      9.69) were included in a prospective randomized cross-over protocol. Sexual
      response was evaluated objectively (duplex ultrasound) and subjectively (self
      reported questionnaire) following vibrator stimuli with the addition of 3 mg SL
      APO or placebo. MAIN OUTCOME MEASURE: Sexual response objective (PSV, EDV, RI)
      and subjective (arousal and lubrication degree and orgasm achievement). Adverse
      events were also recorded. RESULTS: Clitoral hemodynamical changes, particularly
      peak systolic velocity (PSV), were significantly higher with APO (P = 0.003),
      mean increase of PSV poststimulus was 72.50% with placebo (from 9.7 cm/second to
      17.0 cm/second) and 139.14% with APO (from 9.7 cm/second to 21.4 cm/second).
      SUBJECTIVE CHANGES (AROUSAL AND LUBRICATION) WERE ALSO SIGNIFICATIVE WITH APO (P
      < 0.05). CONCLUSION: According to our observations, APO seemed to produce more
      subjective and objective changes in the sexual arousal phase of women with
      orgasmic sexual dysfunction than placebo. Future research is needed to evaluate
      the place of this drug in the treatment of the female sexual dysfunction.

PMID- 16429620
TI  - Antibiotic soaked hydrophilic coated bioflex: a new strategy in the prevention of
      penile prosthesis infection.
AB  - OBJECTIVES: To find conditions that reduce the susceptibility of penile
      prostheses to infection, we studied the effect of coating the surface of
      polyurethane (Bioflex) with a hydrophilic material with and without antibiotics
      in decreasing bacterial colony counts both in vitro and in experiments in rats.
      MATERIALS AND METHODS: The in vitro experiment was performed using seven strips
      each of polyvinylpyrrolidone (PVP)-coated and uncoated polyurethane. These strips
      were dipped in saline for 5 minutes followed by incubation in a suspension of
      Staphylococcus epidermidis (SE) for a period of 10 minutes. Colony counts were
      determined after sonication of strips. For the in vitro experiments, 60 rats were
      used. Thirty animals each had uncoated or coated polyurethane implanted
      subcutaneously. In each group, strips were implanted after dipping them in either
      saline (N = 15) or an antibiotic solution (N = 15) consisting of 1 g/L vancomycin
      and 160 mg/L gentamicin. A bacterial suspension containing SE was then directly
      introduced into the subcutaneous pockets of all the animals prior to closure.
      After 7 days, strips were explanted along with 0.5 x 0.5 cm of surrounding
      tissue, and sonicated. Colony counts were performed on each sonicate. The data
      were analysed using Student's t-test. A P-value less than or equal to 0.05 was
      considered to be statistically significant. RESULTS: The in vitro study
      demonstrated a statistically significant (41%) reduction in the colony count of
      SE within the coated polyurethane strips compared to the uncoated Bioflex strips
      (150 +/- 44.7 CFU vs. 253 +/- 45.0 CFU, respectively, P-value < 0.05). Animal
      studies showed that bacterial CFU was highest in the uncoated Bioflex strip (29
      +/- 24.5 CFU), followed by uncoated Bioflex with antibiotic treatment (24 +/-
      28.1 CFU), coated Bioflex (17 +/- 25.2 CFU) and coated Bioflex with antibiotic
      treatment (13 +/- 16.1 CFU). Antibiotic treatment of coated Bioflex caused a
      significant reduction in the bacterial CFU compared to uncoated Bioflex (13 +/-
      16.1 vs. 29 +/- 24.5 CFU, respectively, P = 0.04). This represents a 55%
      reduction in the bacterial count. While the reduction in the bacterial count in
      the coated Bioflex strip was not statistically different from that in the
      uncoated strip, a trend towards significance was noted with a 41% reduction (P >
      0.05) in bacterial count in the coated Bioflex group compared to uncoated
      Bioflex. CONCLUSIONS: In conclusion, in vitro studies demonstrate a significant
      (41%) reduction in the colony count of SE in PVP-coated polyurethane compared to
      uncoated polyurethane. In vivo study in rats showed that antibiotic treatment of
      PVP-coated Bioflex resulted in a statistically significant reduction (55%) in
      colony count of SE compared to uncoated Bioflex.

PMID- 16429621
TI  - The hydrophilic-coated inflatable penile prosthesis: 1-year experience.
AB  - INTRODUCTION: Penile prosthesis infections are a devastating complication for
      both patient and surgeon. Efforts to reduce the risk of infection from these
      elective procedures are a major focus of research and development by the major
      prosthesis companies. The Titan inflatable penile prosthesis (Mentor Corporation,
      Santa Barbara, CA) is coated with polyvinylpyrrolidone (PVP), a hydrophilic
      substance that reduces bacterial adherence and absorbs and elutes the antibiotics
      the device is immersed in intraoperatively. The Titan device was introduced to
      the American market in September 2002. This study reports the 1-year experience
      in the U.S. with the Titan and compares infection rates with the noncoated Alpha
      1 IPP made by Mentor. MATERIALS AND METHODS: Two thousand three hundred and fifty
      seven Titan prostheses were implanted in the U.S. from September 2002 to August
      2003, compared with the 482 noncoated Alpha-1 IPPs implanted over the same time
      period. Infection rates were compared, along with bacterial culture data. All
      data were collected from Mentor's internal database, as generated from the FDA's
      mandatory reporting of explanted medical devices, and available on the internet.
      RESULTS: The infection rate for the coated Titan IPP was 1.06% (25/2,357). During
      the same time period, the infection rate for the Alpha-1 noncoated prosthesis was
      2.07% (10/482). Staphylococcus species predominated in both groups (9/25 Titan,
      6/10 Alpha-1). CONCLUSIONS: At 1 year of follow-up, the data demonstrate that the
      hydrophilic coating on the Titan IPP confers a significant advantage in reducing
      the rate of infection over the noncoated device. Long-term follow-up on this
      first year database is needed before this innovation is accepted as the standard
      of care for prosthetic surgery. Nevertheless, the theoretical reduction in
      bacterial adhesion conferred by the hydrophilic PVP surface and the ability to
      choose which antibiotic the device is immersed in intraoperatively gives the
      implanting surgeon distinct advantages with this new product.

PMID- 16429622
TI  - Self-reported premature ejaculation and aspects of sexual functioning and
      satisfaction.
AB  - BACKGROUND: Although premature ejaculation (PE) is a common male sexual
      dysfunction, its relevant parameters have not been adequately studied in large
      community-based samples. OBJECTIVE: To examine the diagnostic utility of two self
      report questions based on the DSM-IV-TR definition of PE and to investigate the
      relationship between self-identified PE, sexual functioning, and sexual
      satisfaction in men. METHODS: An Internet survey of general health and aspects of
      sexual functioning and satisfaction was conducted in 2,056 males. Subjects were
      classified as having "probable" or "possible" PE, or as "non-PE" by survey
      responses. RESULTS: A total of 1158 men met the selection criteria (sexually
      active in a stable heterosexual relationship), and 189 (16.3%) were classified as
      having probable PE by reporting they ejaculated before they wished and indicating
      it was "very much" or "somewhat" a problem. Another 188 (16.2%) men reported
      ejaculating before they wished but rated their distress lower and were classified
      as having possible PE. Compared to non-PE men, those with probable and possible
      PE reported significantly worse sexual functioning in 6 of 8 study measures.
      Concern about partner satisfaction was high in all groups. The importance of
      ejaculatory control and the ability to have intercourse for the desired time was
      significantly higher in men with PE as compared to non-PE men (P < 0.01).
      CONCLUSIONS: PE was a common problem, was characterized by a lack of ejaculatory
      control, and was associated with significant effects on sexual functioning and
      satisfaction. Additional research on the sensitivity and specificity of these
      self-report questions should be pursued.

PMID- 16429623
TI  - Tigecycline: an expanded broad-spectrum intravenous antibiotic. Preface and
      summary.

PMID- 16429624
TI  - Justices reaffirm abortion access for emergencies.

PMID- 16429625
TI  - Cancer study was made up, journal says.

PMID- 16429626
TI  - The assisted-suicide decision.

PMID- 16429627
TI  - Fraught issue, but narrow ruling in Oregon suicide case.

PMID- 16429628
TI  - Genetic testing creates new versions of ancient dilemmas.

PMID- 16429629
TI  - Health risks and needs of gay, lesbian, bisexual, transgender, and questioning
      adolescents.

PMID- 16429630
TI  - Roman military diet.

PMID- 16429631
TI  - Potters, occulists and eye-troubles.

PMID- 16429632
TI  - Palaeobotanical evidence from Mollins.

PMID- 16429633
TI  - Cosmetic sets from Late Iron Age and Roman Britain.

PMID- 16429634
TI  - The scope of hypertension.

PMID- 16429635
TI  - The challenge of blood pressure control in patients with ischaemic heart disease
      in Europe.
AB  - The goal of the paper is to summarize the current status of blood pressure
      management in patients with ischaemic heart disease. Recently published results
      from Europe and North America showed that about half of ischaemic heart disease
      patients have their blood pressure over 140/90 mmHg. Moreover, these data provide
      further evidence that poor hypertension management is common in a variety of
      healthcare settings. Although most ischaemic heart disease patients receive blood
      pressure-lowering drugs, still a large proportion of them does not reach the
      recommended treatment goals. During recent years, several attempts were made to
      improve the control of risk factors (among them blood pressure) in patients with
      ischaemic heart disease; however, none of them was definitively successful.

PMID- 16429636
TI  - Epidemiology and prevention of arterial hypertension in Poland.
AB  - The authors review the present situation in epidemiology and prevention of
      arterial hypertension in Poland. In 2002, the NATPOL PLUS survey on
      representative sample of adults (n=3051, age range 18-93) was conducted.
      Prevalence of hypertension, diagnosed on basis of three separate visits, was 29%,
      awareness 67% and efficacy of treatment 12.5%. Thus, in Poland, one-third of 8.6
      million hypertensives are unaware of their disease. A comparison with data from
      other countries should be careful due to the different methods (age range, number
      of readings and visits) used in the studies. The data, in concert with a decrease
      in awareness of one's own blood pressure (from 71% in 1994 to 59% in 2002),
      called for urgent preventive measures. Two large interventions were implemented
      under the National Programme POLKARD in 2003: the Polish 400 Cities Project aimed
      to increase detection and knowledge of hypertension and other risk factors among
      small-town and village communities, and the educational project, A Chance for the
      Young Heart targeted at children aged 11-14 years and using traditional teaching
      methods and an interactive Internet website. Also, an educational and marketing
      programme targeted at public opinion leaders and decision makers (trade unions,
      local governments, healthcare financing authorities, print media and radio, the
      Polish Parliament) started in 1999 and is still in process.

PMID- 16429637
TI  - Lifestyle characteristics and hypertension in the middle-aged population of
      Krakow.
AB  - Hypertension affects nearly one-third of total Polish adult population. Poor
      control of hypertension largely contributes to high cardiovascular disease (CVD)
      mortality in Poland. However, satisfactory hypertension control at the national
      level could be beyond economical conditions. Prevention of hypertension by
      lifestyle modification may be one of the ways to decrease CVD population risk
      attributed to hypertension. The goal was to assess the relation between the
      chance of having hypertension and lifestyle characteristics, i.e. education,
      smoking, physical activity, salt consumption, ethanol consumption and body mass
      index (BMI) in the middle-aged population of the urban population of Krakow. A
      cross-sectional study of a random sample of 1157 women and 1153 men, permanent
      inhabitants of Krakow at age 45-64 years, was carried out by home interview
      followed by a visit in the clinic. There were 66% men and 56% women who had
      hypertension. After adjustment for age, BMI over 27.5 kg/m2 in men and over 25.0
      kg/m2 in women was strongly related to hypertension. In men, odds ratio (OR)
      increased from 1.96 in the group with overweight (27.5 kg/m2 < or = BMI < 30.0
      kg/m2) to 5.33 in the group with obesity (BMI > or = 35.0 kg/m2). In women, OR
      increased from 1.6 in the group with overweight (25.0 kg/m2 < or = BMI < 27.5
      kg/m2) to 13.42 in the group with obesity (BMI > or = 35.0 kg/m2). In men, after
      adjustment for age and BMI, a higher chance of hypertension was found for binge
      drinkers but the result was of borderline significance (p = 0.057). In women,
      moderate alcohol consumption was related to lower chance of hypertension (OR =
      0.72). Women who were current smokers had lower chance of hypertension (OR =
      0.67). No significant relation between smoking and hypertension was found in men.
      After adjustment for age and BMI, there was no significant relation between
      hypertension and physical activity. However, both in men and in women, there was
      a dose effect of leisure time physical activity on the average estimate of the
      chance of hypertension. Education, estimate of sodium consumption and blood total
      cholesterol (TC) were not related to hypertension. The findings confirmed that
      weight control may be a strong tool for preventing hypertension and increasing
      physical activity and refraining from binge drinking may have a protective
      effect.

PMID- 16429638
TI  - Arterial hypertension as a public health issue in Slovenia.
AB  - Hypertension is an important risk factor for cardiovascular diseases. An
      epidemiological survey in 1985 found that the prevalence of hypertension in
      Slovenia was comparable to rates reported from western European countries.
      Awareness of hypertension was poor and only a small fraction of patients had
      their blood pressure under satisfactory control. Since 1985, few population
      studies have been completed; the results suggest that little progress has been
      made in the field of hypertension control. The responsibility for the situation
      lies partly with family physicians, who often fail to react properly to
      uncontrolled blood pressure. Data from the last CINDI survey conducted in 2004
      are more encouraging. Apparently, physicians now provide their patients with more
      information on how to attain their target blood pressure, and the percentage of
      hypertensive patients with controlled blood pressure seems to have increased.
      However, these are only assumptions, which should be verified by a nationwide
      epidemiological study. A pilot survey involving a random sample of the Slovenian
      adult population (about 11,000 subjects) is in progress and will be completed by
      the end of the year 2005.

PMID- 16429639
TI  - Arterial hypertension as a public health issue in the Czech Republic.
AB  - Hypertension increases the risk of coronary heart disease, stroke, peripheral
      arterial disease and heart failure. Five independent cross-sectional surveys for
      cardiovascular risk factors have been conducted in the Czech Republic (1985,
      1988, 1992, 1997/98 and 2000/01), always involving a representative population
      sample aged 25-64 years. Over a period of 15-16 years, there was a statistically
      significant downward trend in population mean systolic (from 133.6 +/- 20.2 to
      128.8 +/- 18.1 mmHg; p < 0.001) and diastolic (from 84.1 +/- 11.3 to 81.4 +/-
      10.0 mmHg; p < 0.001) blood pressure (BP). There was also a significant decrease
      in the prevalence of hypertension in both sexes (from 51.9% to 45.6% in men; p <
      0.001; from 42.5% to 33.0% in women; p < 0.001). Awareness of hypertension
      increased in both sexes, showing higher rates for females (men from 41.4% to
      62.1%; p < 0.001; women from 58.9% to 73.8%; p < 0.001). Hypertension control
      improved significantly over the period of 15/16 years (from 3.9% to 17.9%; p <
      0.001), consistently showing more effective control in women. The significant
      decrease in population mean BP seems to have contributed to the decrease in total
      and cardiovascular mortality in the Czech Republic observed since 1985.

PMID- 16429640
TI  - Hypertension in Latvia--epidemiology and management.
AB  - The aims of investigations were to assess the prevalence of arterial hypertension
      (AH) among Latvian population aged > or = 45 years and to evaluate the current AH
      management situation in Latvia. Four epidemiological databases (Dbases) for
      analyses were selected: Dbases of a randomized urban population of Riga city (in
      1997) and Kuldiga region (in 2000), a Dbase of the DIASCREEN population selected
      by high risk to diabetes from those visiting family doctors (in 2003) and a Dbase
      of a Latvian population selected from those visiting family doctors during 3 days
      in 2005. The prevalence of AH in the urban population was 41.8 +/- 1.4% (with
      61.2% for persons over age 45), in rural population 40.5 +/- 1.6% (with 63.7% for
      those aged above 45). Therapeutic control of AH for patients over 45 years with
      regular medicine intake differed significantly in three samples of the population
      analysed: Riga 7.2 +/- 2.7%, Kuldiga 9.9 +/- 1.6% and DIASCREEN 6.4 +/- 0.8%. The
      addition of another risk factor decreases the control rate, especially in a
      combination of AH and overweight. The most widely prescribed drugs are
      angiotensin-converting enzyme inhibitors (ACEI) 31%, diuretics 21% and beta
      blockers 20% of patients. AH control rate in the case of monotherapy with ACEI
      was 6.9 +/- 0.9%, calcium antagonists 5.6+1.2%, beta-blockers 12.5+2.0% and
      diuretics 3.8+1.4%. The current status of management of hypertension in Latvia is
      discussed.

PMID- 16429641
TI  - Characteristics of blood-pressure control in treated hypertensive patients in
      Croatia.
AB  - The aim of our study was to investigate blood pressure (BP) control and different
      factors with possible influence on BP control in Croatian hypertensive patients.
      In this cross-sectional investigation, a representative sample of target
      populations (primary care physicians and patients) from different parts of
      Croatia was included according to the study protocol. During December 2003 and
      January 2004, we included, according to correctly completed questionnaires, 141
      physicians and 814 hypertensive patients. A controlled BP (BP < 140/90 mmHg) in
      this hypertensive population treated with antihypertensive drugs was in 23% of
      patients. The analysis of BP control according to risk factors showed that
      significantly related with higher levels of systolic or diastolic BP were the age
      (poorer systolic BP control in patients older than 60 years), left ventricular
      hypertrophy, changes of the eye retina, smoking and diabetes mellitus.
      Furthermore, patients from towns closer to the hospital, from urban centers, with
      higher education and employed had significantly lower average BP. According to
      our results of hypertension control in Croatia, there is a need and a possibility
      for the improvement of the quality of hypertension care. The relationship between
      demographic and cardiovascular risk factors with poor BP control should be taken
      into account when treating patients.

PMID- 16429642
TI  - Resistant hypertension.
AB  - The incidence of resistant hypertension remains to be clarified. In this article,
      three categories of resistance are distinguished: resistant patient, resistant
      clinician and refractory hypertension. Inadequate compliance, which in case of
      antihypertensive treatment means taking fewer doses of medications than
      prescribed, remains a significant cause of poor blood pressure control. Among
      most frequent physician-related causes of resistant hypertension, there are
      measurement errors, pseudohypertension, white coat hypertension and therapy
      errors. Careful elimination of patient- and physician-related reasons of
      inadequate blood pressure control should lead to the diagnosis of truly resistant
      hypertension. One of the causes of refractory hypertension may be concomitant use
      of other medications that are known to reduce antihypertensive effect of main
      drugs. Resistance may be associated with increased intravascular volume or fluid
      overload or with sympathetic activation. Modifiable contributing factors
      responsible for resistant hypertension include obesity often coexisting with
      insulin resistance and metabolic syndrome as well as excessive alcohol use and
      cigarette smoking. Another potential cause of refractory hypertension is the
      presence of secondary hypertension. Certain therapeutic modifications are
      essential in resistant hypertension.

PMID- 16429643
TI  - How can we improve the effectiveness of treatment in elderly hypertensives?
AB  - Despite evidence for the benefits of treating hypertension in old age, only a
      small number of elderly patients have adequate blood pressure control. The
      reasons are complex and include a combination of factors related to physician,
      patient adherence to therapy and properties of the antihypertensive drugs.
      Substantial gaps have been documented between the development and dissemination
      of recommendations and their implementation in practice. Older patients are more
      likely to have difficulty with medication adherence. Better compliance
      achievement among the elderly patients should include a complex strategy.
      Moreover, physician information strategies must be improved.

PMID- 16429644
TI  - A patient with high normal blood pressure--should we treat?
AB  - Currently blood pressure (BP) is considered normal (for most subjects) if below
      140 mmHg for systolic and 90 mmHg for diastolic BP. However, the risk of death
      displays an approximately linear relationship with BP levels below this cut-off.
      Therefore more attention is now being paid to the portion of the population
      characterized by BP levels remaining within normal limits but approaching the
      140/90 mmHg level. The 2003 ESH-ESC guidelines define BP between 130/85 and
      139/89 mmHg as "high normal", while the 2003 JNC7 guidelines introduced a new
      category of "prehypertension" (BP between 120/80 and 139/89 mmHg). Both these
      conditions affect a significant portion of a general population. Evidence is
      available that high normal BP is associated with an adverse risk profile and an
      increased risk of cardiovascular events. Therefore lifestyle changes are
      recommended in subjects belonging to this category and some trial data indicate
      that pharmacological treatment may be beneficial in high-risk subjects with high
      normal BP levels. Strong evidence on the benefits of therapeutic intervention in
      this group is, however, still lacking.

PMID- 16429645
TI  - Patient's education in arterial hypertension.
AB  - Non-compliance is an important factor in lack of appropriate control of blood
      pressure. Education of hypertensive patients on about consequences of
      hypertension and benefits of antihypertensive therapy has been reported to
      improve the results of the management of hypertension. The aim of this article is
      to present main factors influencing patients' compliance with antihypertensive
      treatment and the role of educational interventions in the process of therapy.

PMID- 16429646
TI  - [Recommendations to general practice doctors for first line management of
      erectile dysfunction].

PMID- 16429647
TI  - [Molecular pathways of tumour angiogenesis and new targeted therapeutic
      approaches in renal cancer].
AB  - The conventional form of renal cell carcinoma (RCC) is a highly vascular tumour
      with an extremely poor prognosis in the presence of metastases. Significant
      progress has recently been made in the understanding of the molecular mechanisms
      leading to the vascular phenotype of renal cancer In particular, VHL disease
      constitutes a useful study model, as inactivation of the VHL gene leads to
      accumulation of HIF factor, inducing activation of genes such as: VEGF, PDGF,
      EPO, CaIX and TGF-alpha. The fact that VHL inactivation has been found in about
      70% of sporadic renal cancers constitutes the best rationale to target the
      products of these genes. Candidate drugs currently target VEGF, VEGFR, PDGFR and
      tyrosine kinase receptors, which are necessary for intracellular signal
      transduction. The preliminary results of phase II trials in metastatic renal
      cancer, usually as second-line therapy, are very encouraging. The results of
      phase III trials will soon be available, but many studies are already evaluating
      these drugs either as first-line or in combination. Urologists have an
      opportunity to become familiar with these drugs by actively participating in
      trials of adjuvant therapy that will be initiated in the near future.

PMID- 16429648
TI  - ["Penis angina" or the current revolution in erectile dysfunction (ED)].
AB  - Erectile dysfunction (ED) can no longer be neglected by the medical profession,
      as the presence of ED is never entirely benign, but is always a reliable marker
      of a sexual disorder but also (and sometimes especially) a non-sexual disorder
      (physical and/or mental). Its documented association with many chronic diseases
      and high-risk situations is in the process of extending the significance of ED
      beyond the purely sexual domain, as this symptom, easily detected by simple
      clinical interview, appears to be not only a barometer of health, but also a
      warning indicator of situations that can sometimes be dangerous for the patient's
      health. For example, in male populations with a high vascular risk, ED is as
      frequent as diabetes and metabolic syndrome, and must be considered, until proof
      to the contrary, to reflect angina of the penis, i.e. an exercise-induced
      vascular symptom, which has a double warning value: 1) marker of deterioration,
      2) potential prodrome of acute vascular accidents. These close relations between
      ED and cardiovascular disease give a completely different dimension to ED, which
      now constitutes a potential candidate for a new clinical vascular marker and
      possibly, in some cases, a new marker of cardiovascular risk. These unexpected
      roles of revealing factor and clinical marker of multiple health states
      (cardiovascular or other) paradoxically contribute to "desexualization" of ED, as
      sexual health no longer appears to be the major risk involved. In particular,
      they open the realistic perspective of opportunistic and proactive detection of
      ED in well targeted populations for the purposes of primary prevention of
      cardiovascular disease, a public health priority. For all these reasons, the
      development of ED requires a minimal evaluation of the patient's state of health,
      regardless of the doctor's qualification, by clearly distinguishing quality of
      life and health objectives. This modern management of ED is part of an individual
      (humanistic) and social (civic and ethical) approach. This "revolution" complies
      with the requirements of a good quality scientific approach, which comprises the
      concepts of evidence-based medicine and a rational approach to the service
      rendered to the patient, as management of his sexual health (and not his
      sexuality) also comprises management of his general health.

PMID- 16429649
TI  - [PSA doubling time and method of calculation].
AB  - Prostate Specific Antigen (PSA) is currently the best marker for prostate cancer,
      although it is not very specific for this disease. The use of the PSA kinetic, in
      addition to its absolute value, is theoretically very attractive in a large
      number of clinical situations. Based on a review of the literature, the authors
      report the various methods used to study this kinetic, with particular emphasis
      on the most reliable method: the PSA doubling time. After describing the
      definitions and the methods used to calculate this parameter, the authors discuss
      the various clinical situations in which it could be useful: surveillance of
      prostatic tumours after the initial diagnosis in high-risk patients or patients
      refusing treatment, prognostic factor before curative treatment, evaluation of
      the efficacy of curative treatment, prognostic factor of tumour aggressiveness at
      the time of biochemical recurrence after curative treatment or during endocrine
      therapy.

PMID- 16429650
TI  - [Choice of prosthesis in genital prolapse surgery].
AB  - Genital prolapse is an increasingly frequent condition and surgical repair is
      associated with a high recurrence rate. Many technical modifications have been
      proposed in order to improve these results. Synthetic and biological prostheses
      have been developed and marketed often in the absence of well conducted
      randomized controlled studies, and simply claiming the ease of use of a new
      material. However, urologists must be well informed about the efficacy of these
      prostheses, their potential limitations and the associated morbidity. The authors
      report the currently known characteristics of prostheses for genital prolapse
      repair. There is a consensus in favour of large pore size polypropylene
      monofilament mesh. Biomaterials are still under investigation for their
      applications in urology. Randomized, prospective, controlled trials must be
      conducted to determine the long-term efficacy and potential morbidity of the
      various materials used. Morbidity is also related to surgical technique and the
      use of prostheses does not eliminate the need for expertise in prolapse surgery.

PMID- 16429651
TI  - [Postoperative chylous ascites in urology].
AB  - Postoperative chylous ascites is a rare complication after retroperitoneal
      surgery. It is a complex problem associated with nutritionnal and immunological
      consequences. Urologists should be able to manage this complication linked to
      many urological procedures. Incidence of chylous ascites seems to increase with
      time probably because more complex surgical interventions. Diagnosis is usually
      suspected based on clinical abdominal symptoms. Diagnostic paracentesis shows
      milky fluid with high triglyceride and lymphocyte content. Treatment is
      classicaly based on dietary interventions with the goal to decrease fistula's
      lymph flow. Somatostatin analog is a very efficient adjuvant therapy and should
      be used early in the course of treatment. Surgery is usually attempted in
      patients who have failed conservative modalities. Because chylous ascites is
      rare, no clear management guidelines exist. Treatment should be individualized
      and tailored according to severity of lymphatic leakage, its consequences and the
      patient health status.

PMID- 16429652
TI  - [Kidney tumours: single-centre study of 810 patients. Changing features over a
      period of 15 years].
AB  - OBJECTIVE: The Association Francaise d 'Urologie conducted a national
      epidemiological study in 1997. Using our database, we compared our results, up
      dated the epidemiological data and evaluated the differences observed over a
      period of 15 years. PATIENTS AND METHODS: 844 patients operated for kidney tumour
      between 1985 and 2000 were analysed and 810 were included in this study. Survival
      analysis was performed according to the Kaplan-Meier method. Relative risks were
      determined by the Log-Rank test and multivariate analysis was performed with the
      Cox regression model. The limit of significance was 0.05. RESULTS: The mean age
      at the time of diagnosis was 59.6 years (range: 14.6-90.2). Most tumours were
      discovered incidentally by ultrasound. The mean tumour diameter was 61.7 mm
      (range: 20-230). The most frequent surgical operation was radical nephrectomy,
      but there was a tendency towards an increasing number of conservative operations.
      Histology revealed 94% of renal cell carcinomas, with 73% of conventional cell
      carcinomas. The mean follow-up was 49 months (range: 0-197) and 5-year and 10
      year survival rates were 74.9 months and 62.6 months, respectively. Multivariate
      statistical analysis confirmed the prognostic significance of N and M stage,
      Fuhrman grade, histological type, as well as renal capsule invasion. CONCLUSION:
      Our data largely confirm those of the last national study conducted in 1997 as
      well as those of the international literature. Kidney tumours are increasingly
      discovered incidentally, but tumour size and the age of patients remain stable,
      while the number of conservative procedures continues to increase each year In
      addition to the usual prognostic factors, we found that renal capsule invasion
      was an independent prognostic factor.

PMID- 16429653
TI  - [Tubulopapillary tumours of the kidney: prognostic value and therapeutic
      implications of the distinction between type 1 and type 2 based on a series of 58
      cases].
AB  - OBJECTIVE: The purpose of this study was to demonstrate the prognostic value of
      subdivision of tubulopapillary tumours into 2 histological subtypes and to
      discuss the therapeutic implications. MATERIALS AND METHODS: This was a single
      centre retrospective study of 58 cases from a series of 414 patients operated for
      renal cancer between 1988 and 2001 based on review of histology slides (biopsies
      and operative specimens). The radiological assessment was based on ultrasound
      reports and review of CT scans. Karyotypes were described by cytogenetic
      analysis. RESULTS AND DISCUSSION: Tubulopapillary tumours represented 14% of all
      kidney tumours with a male prevalence of 77% and a mean age of 56.5 years. The
      overall mean follow-up was 62.6 months. Treatment consisted of 25 right radical
      nephrectomies, 29 left radical nephrectomies and 4 partial nephrectomies. 84% of
      tumours were low-grade and 80% were low stage T1 or T2. Multifocal lesions were
      observed in 31% of cases. Synchronous bilateral lesions were observed in 12% of
      cases. The 5-year survival was 95% and the 10-year survival was 87%, correlated
      with stage, grade, tumour diameter, presence of necrosis and low enhancement.
      According to the data reported by Delahunt, 2 subtypes can be distinguished: Type
      I tumours (75%) with low grade and low stage were correlated with a high rate of
      multifocal lesions (30%) with a genetic predisposition. Type 2 tumours (25%),
      usually unifocal, were correlated with a higher grade and stage, confirmed by
      their poorer prognosis. Biopsy allows a distinction of the type and grade of the
      tumour. CONCLUSIONS: In our series, for equivalent mean tumour diameters (55 mm),
      tubulopapillary tumours treated by radical nephrectomy had a good prognosis
      regardless of their subtype. Classification of the tumour by biopsy prior to
      surgery could have implications for therapeutic management. For type 1
      tubulopapillary tumours identified on preoperative biopsy, we propose radical
      nephrectomy due to the high risk of multifocal lesions (30%). Although partial
      nephrectomy may be indicated for type 1 tubulopapillary tumours less than 4 cm,
      the patient must be informed about the risk of recurrence and the importance of
      long-term follow-up. Studies including a larger number of patients must be
      conducted to compare the survival associated with type 2 tumours compared to that
      of the classical histological subtype.

PMID- 16429654
TI  - [Retroperitoneal laparoscopic treatment of parapelvic renal cysts: report of 5
      cases].
AB  - OBJECTIVES: Renal cysts of the sinuses or parapelvic cysts constitute a rare form
      of renal cyst, usually associated with low back pain. Symptomatic forms may be
      treated by percutaneous aspiration, but the treatment of these cysts has changed
      considerably over recent years due to the proximity of the renal hilum.
      Percutaneous treatment is now contraindicated due to its high complication rate,
      and open surgery is an invasive technique. Laparoscopy appears to be the most
      appropriate and most effective solution. PATIENTS AND METHODS: The authors report
      five cases of parapelvic renal cysts all presenting with renal colic and
      diagnosed by ultrasound, and confirmed by CT in three cases. Treatment consisted
      of retroperitoneal laparoscopy using four trocars allowing cyst resection with no
      intraoperative complications or conversion. RESULTS: The mean operating time was
      55 minutes (range: 40 to 70 minutes). The postoperative course was uneventful and
      all patients were discharged on postoperative D1 or D2. No recurrence was
      observed after a mean follow-up of 6 months (range: 3 to 15 months). CONCLUSION:
      Retroperitoneal laparoscopic treatment of parapelvic renal cysts is an effective
      approach, with a low morbidity and less postoperative pain, a short convalescence
      period and good cosmetic results.

PMID- 16429655
TI  - [Complications and functional results of Hautmann ileal bladder in a series of 87
      patients].
AB  - OBJECTIVES: To retrospectively evaluate the complications, urinary reservoir
      function and quality of life of patients with Hautmann ileal bladder after
      cystectomy for bladder urothelial carcinoma. METHODS: From 1994 to 2004, 87
      patients with a mean age of 61.1 years underwent total cystoprostatectomy (n = 85
      men) or radical cystectomy (n = 2 women) with Hautmann replacement
      enterocystoplasty. The mean follow-up was 40.7 months. Continence, quality of
      voiding, and quality of life were evaluated by self-administered questionnaires
      (continence questionnaire, DITROVIE score, I-PSS score). RESULTS: The early
      complication rate was 30.1%, including 6.9% related to the ileal bladder. The
      late complication rate was 33.6%, including 20.9% related to the ileal bladder.
      Four patients died during the perioperative period, 14 patients (17%) died from
      progression of their cancer and 7 patients (8%) died from an independent cause.
      One patient was lost to follow-up. Questionnaires were sent to 56 patients and 52
      replies were received: 96.2% of patients were continent during the day, 53.8%
      were continent at night. 4.9% of patients performed self-catheterization for
      chronic urine retention, 90.4% of patients were satisfied with their replacement
      bladder and only 5.8% of patients had an altered quality of life. CONCLUSION:
      Despite a considerable morbidity rate and a significant nocturnal incontinence
      rate, the orthotopic Hautmann W-shaped ileal bladder does not appear to alter the
      patients' quality of life.

PMID- 16429656
TI  - [Comparison of the response to I-PSS according to the mode of administration of
      the questionnaire: by the doctor or self-assessment by the patient].
AB  - OBJECTIVE: To compare the response to I-PSS according to its mode of
      administration (by the doctor versus self-assessment). METHODS: 388 patients were
      included during the 3 months following a diagnosis of benign prostatic
      hyperplasia. The general practitioner completed the I-PSS and gave an I-PSS
      questionnaire to the patient to be completed at home and returned in a reply-paid
      envelope to the data entry centre. The Bland & Altman method was used to
      visualize individual differences and to quantify the bias between the two modes
      of evaluation. RESULTS: The doctor overestimated the I-PSS by an average of 1.3
      points [95% CI: 0.9-1.7]. In 42% of patients, these individual differences were 3
      points or more. Significant overestimation was confirmed at 6, 12 and 18 months
      of follow-up. CONCLUSION: A significant bias was demonstrated according to the
      mode of administration of the I-PSS. We therefore recommend that the same mode of
      administration should be maintained during clinical trials.

PMID- 16429657
TI  - [Effect of dutasteride on reduction of intraoperative bleeding related to
      transurethral resection of the prostate].
AB  - OBJECTIVE: The pharmacological action of 5-alpha-reductase inhibitors (5-ARI)
      would reduce angiogenesis associated with benign prostatic hyperplasia (BPH),
      thereby decreasing peroperative bleeding during transurethral resection of the
      prostate (TURP). Dutasteride, a double inhibitor of 5-alpha-reductase iso-enzymes
      types 1 and 2, was not been previously studied in the context of reduction of
      peroperative bleeding related to TURP. MATERIAL AND METHODS: We conducted a
      multicentre, randomized, double-blind, placebo-controlled, parallel group study
      to evaluate the efficacy of dutasteride 0.5 mg per day, in peroperative bleeding
      related to TURP for BPH in patients over the age of 50 years with a prostatic
      volume greater than 30 cm3. Treatment was administered for 4 weeks before the
      operation. The primary endpoint was haemoglobin, expressed in grams, and
      expressed in relation to the weight of prostate resected, also expressed in
      grams. RESULTS: 59 patients were evaluated (32 treated with dutasteride and 27
      treated with placebo). A significant difference in peroperative bleeding was
      observed between the dutasteride group (1.944 +/- 1.816 g of Hb/g of prostate
      resected) and the placebo group (1.401 +/- 1.021 g of Hb/g of prostate resected).
      Preoperative treatment was well tolerated. CONCLUSION: The working hypothesis of
      the study was not confirmed due to the low bleeding rate in the placebo group and
      the results suggest that a longer duration of treatment with dutasteride would
      reduce intraoperative and postoperative bleeding in TURP.

PMID- 16429658
TI  - [Effect of dutasteride on reduction of plasma DHT following finasteride therapy
      in patients with benign prostatic hyperplasia].
AB  - INTRODUCTION: Dihydrotestosterone (DHT) is a steroid hormone derived from
      testosterone, by the action of two distinct isoenzymes (type 1 and 2) of 5-alpha
      reductase. Dutasteride is a specific selective inhibitor of the two isoenzymes,
      while finasteride is a selective inhibitor of type 2 -alpha-reductase. The
      working hypothesis is that the double 5-alpha-reductase inhibition induced by
      dutasteride therapy for 6 weeks should induce a supplementary reduction of plasma
      DHT levels compared to a parallel patient group continuing finasteride therapy
      over the same period. MATERIALS AND METHODS: In this prospective, two-centre,
      double-blind study, 21 patients previously treated by finasteride 5 mg for benign
      prostatic hyperplasia (BPH) for at least 6 months were randomized to receive
      either dutasteride 0.5 mg, or finasteride 5 mg daily for 6 weeks. RESULTS: The
      mean relative variation of plasma DHT was 67.3% +/- 16.16% in the dutasteride
      group and 30.3% +/- 59.8% in the finasteride group. The reduction of DHT was
      numerically greater and more constant in the dutasteride group than in the
      finasteride group at 6 weeks; such a tendency was already observed after two
      weeks of treatment with dutasteride. Nevertheless, these differences were not
      statistically significant. Both medications were well tolerated and the only
      treatment-related adverse event (epigastric pain) was reported in the finasteride
      group. CONCLUSIONS: The working hypothesis was therefore not statistically
      confirmed. It is difficult to conclude whether this reflects poor patient
      compliance with long-term finasteride for BPH or variability of response in
      patients with good compliance with treatment.

PMID- 16429659
TI  - [Infertility and testicular tumour based on a series of 25 patients].
AB  - OBJECTIVES: To evaluate the frequency of testicular tumours in infertile men and
      to specify their clinical, ultrasound and histological characteristics. MATERIAL
      AND METHODS: Retrospective study of all partial or total orchidectomies performed
      between January 1995 and April 2004. During this period, 3,000 new patients
      consulted for assessment of infertility. The clinical, laboratory and ultrasound
      assessment was identical for each patient. RESULTS: Twenty-six testicular tumours
      were operated in 25 patients, i.e. 0.83% of the infertile men who consulted our
      department. Six tumours were clinically palpable (23%) and 20 (77%) were
      discovered on ultrasonography. The size of nodules ranged between 4 and 49 mm.
      Twenty-three radical orchidectomies and only 3 partial orchidectomies were
      performed, as 96% of testes presenting a nodule were hypotrophic. Histological
      examination demonstrated 15 Leydig cell tumours (58%), 8 seminomas (30%), mature
      teratoma,1 Sertoli cell tumour, and 1 burnt-out tumour. Nine (36%) patients had a
      history of cryptorchidism. Tumour markers were normal in 24 of the 25 patients
      (96%). All nodules were hypoechoic. All tumours were classified as pT1 N0 M0 and
      no recurrence has been observed to date. CONCLUSION: The incidence of testicular
      tumours in infertile men is much higher than in the general population. This
      incidence ranges between 0.35% and 0.83% according to various studies. A
      urological and andrological assessment should therefore be performed in all men
      presenting with infertility.

PMID- 16429660
TI  - [Improvement of the recruitment of surgery interns derived from the Epreuves
      Nationales Classantes (National-Ranking Exam): practical solution applied to
      urology].
AB  - OBJECTIVES: To analyse the value of an urology initiation session proposed to
      young interns to improve recruitment of the discipline since the introduction of
      the new National-Ranking Exam (NRE). MATERIALS AND METHODS: In October 2004, the
      77 interns appointed to surgery in Paris on the basis of the ENC participated in
      a one-day urology initiation session organized by the AFUF, at the AP-HP School
      of Surgery. All interns were given a questionnaire at the beginning of the
      session to record the following data: age, gender, teaching hospital, a student
      attachment in urology and desired specialization as a function of the surgical
      training programmes proposed by the ENC. Items concerning the desired
      specialization were resubmitted to the interns at the end of the session.
      RESULTS: Population. 77 interns, 48 females (62.3%) and 29 males (37.7%) with a
      mean age of 25.2 +/- 5 years (range: 23-31). 55 interns had trained at a Parisian
      teaching hospital (67%) and 22 (28.6%) had trained at a provincial teaching
      hospital. 16 interns (20.8%) had completed at least one urology attachment during
      their medical training. Desired specialization. Orthopaedics was the discipline
      most frequently cited (n = 20; 26%). Urology was chosen by 8 interns (10.40%),
      who had all completed an urology attachment during their medical training. At the
      end of the urology initiation session, another 8 interns expressed the desire to
      specialize in urology. Of the 16 potential urology interns, 9 (56.2%) confirmed
      that their decision was final. CONCLUSION: Urology occupies a special place and
      remains a popular surgical speciality among students. Organization of practical
      sessions constitutes a solution to inform, create an emulation and motivate
      surgery interns to choose urology.

PMID- 16429661
TI  - [Mechanical evaluation of various suburethral tapes used for the treatment of
      stress urinary incontinence].
AB  - OBJECTIVE: The objective of this study is to compare the mechanical
      characteristics of a series of suburethral tapes marketed for the treatment of
      stress urinary incontinence, often considered to be identical in the clinical
      practice. MATERIAL AND METHOD: Six suburethral tapes were studied: TVT (Gynecare
      Ethicon, USA), IVS (Tyco Healthcare, USA), Sparc (AMS, USA), Uretex (Sofradim,
      France distributed by BARD), I-stop (CL medical, France), and Uratape (Porges,
      France). The surface was studied by scanning electron microscopy. Mechanical
      properties were evaluated on an Instron traction apparatus equipped with a 500
      Newton transducer and elongation was performed at a rate of 10 mm/min.
      Deformation curves, Young's elastic modulus, and maximum load were calculated.
      Possible release of particles was investigated by weighing each sample before and
      after gentle 0.01 kN traction. RESULTS: From a purely mechanical point of view,
      completely opposite properties were observed. The maximum load ranged from 0.012
      +/- 0.002 to 0.047 +/- 0.013 kN. Young's elastic modulus ranged from 4.31 +/- 1.1
      to 41.99 +/- 14.3 Mpa. Maximum deformity ranged from 31% to 108%. Release of
      particles was estimated, according to the tape, to represent a variation of the
      initial weight of between 0.01% and 8.5%. CONCLUSION: It is difficult to compare
      tapes that are theoretically marketed for the same application, suggesting that
      the same tape should probably not be used for the same application. Clinicians
      must more extensively evaluate the required properties. The authors believe that
      tapes with a high elastic modulus should be proposed for transobturator
      procedures to provide real perineal support, while tapes with a lower elastic
      modulus should be used for retropubic techniques.

PMID- 16429662
TI  - [Transvaginal treatment of anterior vaginal prolapse with collagen implant
      transobturator fixation].
AB  - INTRODUCTION: Prolapse is a common disease with a multifactorial aetiology that
      may be either isolated or associated with other pelviperineal defects. Surgical
      reconstruction of the infravesical anterior segment by isolated colpomyorraphy of
      prolapse is often disappointing with a recurrence rate of 40% according to the
      literature. Several procedures, consisting of strengthening of the anterior
      vaginal wall have been proposed. The use of prosthetic material has
      revolutionized the treatment of cystocele with a reduction of the recurrence rate
      but at the price of a poorly defined morbidity. Few published studies have
      assessed the use of xenogeneic tissue in the treatment of anterior vaginal
      prolapse. The objective of this study was to demonstrate the feasibility,
      morbidity and short-term results of the use of Pelvicol reticulated collagen mesh
      in the treatment of cystoceles. OBJECTIVE: To demonstrate the feasibility and
      short-term results of the transvaginal treatment of cystoceles using collagen
      implant transobturator (TO) fixation. Many new prosthesis-based techniques are
      designed to decrease recurrences after repair without prosthesis, but they are
      often non-standardized, with inadequate evaluation and insufficient follow-up. In
      contrast with synthetic material, few published studies have investigated the use
      of xenogeneic tissue. PATIENTS AND METHODS: Twenty-eight patients with a mean age
      of 70.6 years (range: 53-84) with grade 2 and 3 cystocele and a history of
      transvaginal prolapse repair in 7 cases, were operated by 2 operators according
      to an identical technique: the bladder was dissected via a transvaginal approach
      and a 4 x 7 cm porcine dermis collagen prosthesis was then placed underneath the
      bladder and fixed, at its anterolateral angles via a TO approach to the midline
      suburethral part by a resorbable suture. Vaginal hysterectomy was associated in
      11 cases. RESULTS: The mean specific prosthesis insertion time was 25 minutes. No
      intraoperative complication and no serious bleeding were reported. The mean
      hospital stay was 3.6 days (range: 2-9). The mean follow-up was 8 months (range:
      6-16). One case of mesh expulsion was observed on D15, followed by complete
      healing without recurrence of the cystocele. One case of slight pain of the
      medial aspect of the thigh was observed with a favourable secondary outcome. The
      postoperative anatomical results showed complete repair of the prolapse at 1
      month and on review. Two cases of de novo SUI were treated by transobturator
      suburethral tape with a good postoperative result. CONCLUSION: The technique is
      feasible, simple, safe and ensures very satisfactory short-term results. Follow
      up of these patients will be continued.

PMID- 16429663
TI  - [Preliminary results of endoscopic treatment of vesicoureteric reflux in
      children. Prospective comparative study of Deflux vs. Coaptite].
AB  - INTRODUCTION: The objective of this study is to compare the short-term and medium
      term efficacy of Coaptite versus Deflux in the endoscopic treatment of
      vesicoureteric reflux in children. MATERIALS AND METHODS: Over a period of 24
      months, a cohort of 31 children with 44 refluxing vesicoureteric units were
      treated alternately by either Deflux implants (Group I, 24 refluxing units) or
      Coaptite implants (Group II, 20 refluxing units). This series comprised 40
      solitary ureteric systems and 2 complete duplications. The two groups were
      comparable in terms of age at the time of the operation and distribution of
      severity of reflux. The quantity of product injected was identical in the 2
      groups: 0.5 cc per ureter. All patients in group II received only one injection,
      while 2 Deflux injections were necessary in 2 patients and 3 injections were
      necessary in 1 patient in group I. All children were reviewed by ultrasound and
      retrograde cystography 3 months after the operation. RESULTS: Reflux, regardless
      of grade, resolved in 70% of cases in the 2 groups (no significant difference).
      The cure rate was 75% for grade II and III in group I and 62.5% (grade II) and
      70% (grade III) in group II, with no significant difference between the 2 groups.
      Two cases of grade IV reflux were cured after a single implantation of Coaptite
      in 1 case and Deflux in the other case. Complications, such as ureteric stasis or
      haemorrhage at the injection site, were not observed. CONCLUSION: Although the
      efficacy of endoscopic treatment has now been clearly established, the choice of
      material to be injected is still controversial. This preliminary study did not
      reveal any significant difference in terms of cure rate, regardless of grade,
      between patients treated with Coaptite or Deflux. The medium-term and especially
      the long-term morbidity of these products still needs to be evaluated.

PMID- 16429664
TI  - [Spongioplasty in the treatment of hypospadias].
AB  - OBJECTIVE: Hypospadias is a frequent anomaly, for which many repair techniques
      have been proposed. In 2000, we described a method of one-stage anatomical
      correction, called spongioplasty. The present study evaluated the functional and
      cosmetic results of this technique. MATERIAL AND METHODS: 154 patients treated by
      this technique over a 10-year period were reviewed. All complications reported
      were compared according to the anatomical form, age at the time of surgery, and
      year of operation. RESULTS: We demonstrate a learning curve lasting about 6
      years, after which the complication rate of this technique becomes lower than
      that associated with other methods, particularly for distal forms. In our
      experience, this complication rate is lower for an operative age between 5 and 8
      months. CONCLUSION: In the light of these results, this type of surgery can be
      proposed at an earlier age than other techniques.

PMID- 16429665
TI  - [A striking image].

PMID- 16429666
TI  - [Lomboscopic surgery for renin-secreting tumour].
AB  - Renin-secreting tumour is a rare, benign entity, responsible for hypertension due
      to secondary hyperaldosteronism. It must be treated surgically. In the light of a
      review of the literature, the authors report the first published case of
      resection of a juxtaglomerular tumour of the kidney by laparoscopic partial
      nephrectomy using an ultrasound scalpel.

PMID- 16429667
TI  - [Solitary fibrous retroperitoneal tumour: report of two cases].
AB  - Solitary fibrous tumours are benign tumours, described for the first time by
      Klemperer and Rabin in 1931. They are mesenchymal tumours which usually arise in
      the pleura, while retroperitoneal sites have been rarely described. The authors
      report two cases of very large retroperitoneal tumours in two men aged 58 and 47
      years, respectively, who consulted for abdominopelvic vaulting associated with
      gastrointestinal and urinary disorders. Ultrasound-guided biopsy suggested the
      diagnosis preoperatively in one case. In the light of these cases, the authors
      present a review of the main extrapleural sites described to date, as well as the
      most characteristic radiological, histological and immunohistochemical features
      in order to facilitate the diagnosis.

PMID- 16429668
TI  - [Inverted papilloma of the ureter: a case report].
AB  - Inverted urothelial papilloma is a rare tumour particularly in the ureter. It is
      difficult to distinguish microscopically from low-grade urothelial carcinoma,
      inverted type. The authors report a new case of ureteric inverted papilloma in a
      64-year-old man and discuss the histological diagnostic criteria, clinical
      features and prognosis of this tumour.

PMID- 16429669
TI  - [Bladder leiomyoma treated by transurethral endoscopic resection].
AB  - We report a case of intravesical bladder leiomyoma in a 47-year-old patient
      presenting with recurrent macroscopic haematuria. The diagnosis was strongly
      suspected on CT and cystoscopy. Treatment consisted of transurethral resection of
      the mass. No recurrence has been observed with a follow-up of two years. In the
      light of this case, the authors discuss the diagnosis and treatment of bladder
      leiomyoma.

PMID- 16429671
TI  - [Florid glandular cystitis].
AB  - INTRODUCTION: Florid glandular cystitis is a rare benign bladder tumour, which
      can simulate a malignant lesion. MATERIAL AND METHODS: Over a period of fifteen
      years, we have observed one case of recurrent florid glandular cystitis. RESULTS:
      This 48-year-old patient presented with terminal haematuria and right low back
      pain with a history of endoscopic resection of a bladder tumour. Ultrasound
      showed a solid mass of the bladder base. Intravenous urography showed bilateral
      uretero-caliceal dilatation, predominant on the right, with a filling defect of
      the bladder base. CT urography showed invasion of the vesicoprostatic fat and
      endoscopy revealed a trigonal tumour 5 cm in diameter. Histology concluded on
      florid glandular cystitis of the intestinal type. Improvement of the symptoms was
      observed on the fifth postoperative day after resection of the tumour.
      CONCLUSION: Florid glandular cystitis is a rare benign bladder tumour. The
      diagnosis is based on clinical examination, radiology and histological
      examination. Treatment is essentially surgical.

PMID- 16429670
TI  - [Encrusted cystitis].
AB  - Encrusted cystitis is a chronic inflammation of the bladder mucosa associated
      with calcified deposits induced by numerous bacteria in an alkaline medium.
      Corynebacterium urealyticum or group D2 is most frequently incriminated.
      Encrusted cystitis is a rare disease with non-specific clinical features. The
      diagnosis may be suspected on imaging, but is often only established later on
      histological findings. Treatment of this disease is based on appropriate
      antibiotics with acidification of the urine. The authors report a new case of
      encrusted cystitis in a 78-year-old woman and review the literature on encrusted
      lesions of the urinary tract.

PMID- 16429672
TI  - [Primary transitional cell carcinoma of the bulbar urethra].
AB  - The authors report a case of low-grade primary papillary transitional cell
      carcinoma of the bulbar urethra in a 61-year-old man treated by endoscopic
      resection with a favourable outcome and no recurrence with a follow-up of 11
      years.

PMID- 16429673
TI  - [Well differentiated paratesticular liposarcoma in adults].
AB  - The authors report a case of well differentiated paratesticular liposarcoma in a
      41-year-old patient. This is a rare tumour (about one hundred cases have been
      reported in the literature), which essentially arises from the spermatic cord.
      Clinical and radiological signs are nonspecific and the diagnosis is generally
      based on histological examination of the operative specimen. Due to the
      histological similarities, all specimens of benign lipoma must be examined for
      the presence of well differentiated liposarcoma. Treatment consists of
      transinguinal radical orchidectomy, sometimes with resection of adjacent
      structures. The prognosis is generally better than that of other paratesticular
      sarcomas. Adjuvant radiotherapy may be indicated in locally advanced masses or in
      the case of incomplete resection.

PMID- 16429674
TI  - [Victor Rochet (1860-1934), founder of Lyons' Urology and his contribution to
      surgical treatment of hypospadias].
AB  - Through this article we present the scientific portrait of Victor Rochet, founder
      of Lyons' Urology, and we emphasize on his two procedures of hypospadias'
      surgical treatment.

PMID- 16429675
TI  - [Re: "Current role of chemotherapy in the treatment of hormone-resistant
      metastatic prostate cancer" by Xavier Breton, Eric Lechevallier, Christian
      Coulange, Prog. Urol., 2005, 15, 398-404].

PMID- 16429677
TI  - [Transobturator surgery of female stress urinary incontinence: outside in or
      inside out? Comparative anatomical study. By Spinosa J.P., Dubuis P.Y., Riedere
      B. Prog. Urol., 2005, 15 (4):700-706].

PMID- 16429676
TI  - [Re: "Laparoscopic sacrocolpopexy: comparison of a non-resorbable prosthetic band
      (Mersuture) with SIS collagen matrix (Surgesis ES). By Michael Grynberg, Frederic
      Dedecker, Frederic Staerman. Prog. Urol., 2005, 15, 751-755].

PMID- 16429678
TI  - Survey reveals nurse dissatisfaction over AfC.

PMID- 16429679
TI  - Questions remain over AfC implementation.

PMID- 16429680
TI  - Nurses pay the price for media health scares.

PMID- 16429682
TI  - Has nurse leadership lost its way?

PMID- 16429681
TI  - Should nurses be allowed to diagnose?

PMID- 16429683
TI  - Improving the hospital experience for older people.
AB  - The National Service Framework for Older People states that older people's care
      in hospital should be delivered by staff who have the right set of skills to meet
      their needs. This article outlines an innovative project to enhance the knowledge
      and skills of staff in Portsmouth Hospitals NHS Trust.

PMID- 16429684
TI  - Tuberculosis.

PMID- 16429685
TI  - The liver. Part 5: acute liver failure.
AB  - Clinical complexity presents health professionals with a significant challenge if
      a patient with ALF is to survive. While efforts to develop pharmacological
      therapies and biomechanical techniques serve as a bridge to spontaneous recovery,
      liver transplantation is the most successful treatment for most cases.

PMID- 16429686
TI  - Factors contributing to poor concordance in health care.
AB  - Nurses may expect patients to follow advice but they do not always do so. This is
      called non-concordance or non-compliance. Nurses are in a prime position to
      support and develop a model of communication where patients are asked about the
      extent to which they want to play a part in decision-making about their health.

PMID- 16429687
TI  - Carbamazepine.

PMID- 16429688
TI  - Sexual health assessment in a general practice travel clinic.
AB  - Sexual health and travel health are two distinct areas yet they are linked in the
      context of a travel health consultation. Sexual health provision within general
      practice is inconsistent and dependent on the attitudes and training of practice
      nurses and GPs--some of whom may be too embarrassed to discuss sex. However, if
      practice nurses are to provide holistic and comprehensive travel advice, sexual
      health, its language and its challenges must be embraced and applied in the
      consultation.

PMID- 16429689
TI  - How to use non-verbal signs in assessments of suicide risk.
AB  - Many tools routinely used by health professionals to assess suicide risk rely
      heavily upon verbal information received from patients during the course of an
      interview, despite the majority of interpersonal communication in the health care
      setting being of a non-verbal nature. A verbal statement of suicidal intent may
      be of little value as the person may be performing according to interviewer
      expectations and interview context. To facilitate more accurate and meaningful
      suicide risk assessment and effective clinical judgement, the non-verbal
      components of patient behaviour must be addressed and more specifically measured.

PMID- 16429690
TI  - Holistic care aids sexual health.

PMID- 16429691
TI  - Developing integrated paediatric continence services.
AB  - The Paediatric Continence Forum is a coalition of specialist clinicians, nurses
      and industry representatives, and is chaired by Penny Dobson. It came together in
      2003 through a mutual concern about the fragmented and under-resourced nature of
      NHS services for children with bladder and bowel problems, and aimed to highlight
      the need for dedicated services for these problems and to campaign to have
      continence included in the National Service Framework for Children, Young People
      and Maternity Services (NSF) (DoH, 2004a).

PMID- 16429692
TI  - Faecal incontinence products and quality of life.
AB  - Faecal incontinence has been defined as the involuntary or inappropriate passage
      of faeces (Royal College of Physicians, 1995). It is a distressing and isolating
      problem that affects people of all ages, with an estimated incidence of 1-2 per
      cent of the population (Soffer and Hull, 2000). Many people must rely on
      continence products to manage this stigmatising and embarrassing problem.

PMID- 16429693
TI  - A nurse-led ward attender service in urology.
AB  - The Department of Urology at East Surrey Hospital, Redhill, serves a catchment
      population of 400,000 people. It provides acute and elective urological services
      to both adults and children. Outpatient clinic services are provided at Crawley,
      Horsham, Dorking, Caterham, Oxted, and East Grindstead.

PMID- 16429694
TI  - Benefits of inclusive continence assessments for sexual health.
AB  - Urinary incontinence can affect every aspect of a person's life, including
      her/his sexual health. It is more common in women than in men, and is defined as
      an involuntary leakage of urine (Abrams et al, 2002). Stress urinary incontinence
      and urge incontinence are the most common forms of incontinence in women.

PMID- 16429696
TI  - Making a big event out of emergency care nursing.

PMID- 16429697
TI  - The oral cavity and overall health.

PMID- 16429695
TI  - Treatments for stress urinary incontinence.
AB  - Stress urinary incontinence (SUI) is a common problem among women, particularly
      after childbearing. While it is not in itself life-threatening, it inevitably
      impairs quality of life, causing embarrassment and even social isolation--this is
      often both the reason that people with SUI seek medical help and the method of
      measuring the success of treatment. A range of treatment and management options
      is available for dealing with this distressing condition.

PMID- 16429698
TI  - Periodontitis and cardiovascular disease: a review of shared risk factors and new
      findings supporting a causality hypothesis.
AB  - Periodontitis is a common chronic disease worldwide. It is a major cause of tooth
      loss among adults and recently has been suggested to increase the risk for
      developing several systemic diseases, including cardiovascular disease.
      Populations are not equally affected by periodontal disease because there are
      several environmental and host factors modulating susceptibility. Cardiovascular
      disease shares many of the same susceptibility factors. The purpose of this
      report is to identify risk factors and indicators common to periodontitis and
      cardiovascular disease, and also to discuss their possible interrelationship in
      this association. Recent findings to support a causal association between the 2
      conditions are also presented.

PMID- 16429699
TI  - Zirconium implant abutments: fracture strength and influence of cyclic loading on
      retaining-screw loosening.
AB  - OBJECTIVE: The purpose of this study was to determine the fracture strength of
      zirconium implant abutments and the torque required to unfasten the retaining
      screw before and after applying cyclic loading to the implant-abutment assembly.
      The dynamic behavior and stress distribution pattern of zirconium abutments were
      also evaluated. METHODS AND MATERIALS: Static and cyclic loading of 7 XiVE
      implants with straight Cercon zirconium abutments were simulated under worst-case
      conditions. Cyclic loading tests were performed via a servohydraulic dynamic
      testing machine at loads between 100 and 450 N, for up to 5 million loading
      cycles, at 15 Hz. The dynamic behavior of the zirconium abutments was analyzed by
      finite element modeling and Pro/Mechanica software, comparing van-der-Mises and
      maximum stress levels. RESULTS: Cercon zirconium-ceramic abutments exhibited a
      maximum fracture strength of 672 N during static loading and 269 N at 800,000 to
      5 million cycles runout point, and 403 N at 10,000 cycles runout point during
      cyclic loading. The mean torque value required to unfasten the abutment retaining
      screws after (initial) tightening was 21 Ncm +/- 1 and 20 Ncm +/- 1 (measurement
      accuracy +/- 2 Ncm) after loading with up to 5 million cycles respectively.
      Torque values decreased minimally and screw loosening did not occur. Within the
      limited number of test specimens (7), the difference was statistically
      significant (P = .015). FEM analysis displayed higher stress peaks up to 800 MPa
      at the cervical aspect of the zirconium abutment and at the apical third of its
      retaining screw at an external load of 250 N. CONCLUSION: Within the limitations
      of this study, zirconium implant abutments exceeded the established values for
      maximum incisal bite forces reported in the literature and tightly fit into the
      titanium implant after several millions of loading cycles.

PMID- 16429700
TI  - A new design for all-ceramic inlay-retained fixed partial dentures: a report of 2
      cases.
AB  - In a previous clinical study, all-ceramic resin-bonded 3-unit inlay-retained
      fixed partial dentures (IRFPDs) had a significantly worse outcome in the
      posterior region than did crown-retained 3-unit FPDs made from the same material.
      Debonding or fractures were causes of failure. To improve the clinical outcome of
      IRFPDs, a new framework design was developed: (1) The inlay retainers were made
      out of CAD/CAM-manufactured zirconia ceramic to improve fracture resistance, and
      additional veneering of the inlays was omitted. (2) The inlay retainers were
      completed with a shallow occlusal inlay (1-mm minimum thickness) and an oral
      retainer wing (0.6-mm minimum thickness). The wings were designed to reduce
      stress on the inlay retainer caused by torsion forces when the FPD is loaded
      nonaxially and to increase the enamel adhesive surface area. The pontic was
      circumferentially veneered with feldspathic porcelain. The clinical and
      laboratory procedures of this new treatment modality are described, and 2
      exemplary clinical cases are presented. This new preparation and framework design
      might improve the clinical outcome of all-ceramic resin-bonded IRFPDs. However,
      adequate evidence of long-term safety and efficacy is required before this new
      design can be recommended for general clinical practice.

PMID- 16429701
TI  - Influence of conditioning time on enamel adhesion.
AB  - OBJECTIVE: The aim of this study was to calculate enamel bond strengths of 4 self
      etch adhesives in function of conditioning time. METHODS AND MATERIALS: Sixty
      proximal surfaces of 30 extracted human molars were roughened and assigned to 4
      self-etch adhesives: AdheSE (Ivoclar Vivadent), Adper Prompt L-Pop (3M Espe),
      Clearfil SE Bond (Kuraray America), and Tyrian SPE/One-Step Plus (Bisco). Prime &
      Bond NT (Dentsply) was used as the total-etch control. For 30 surfaces, the
      adhesives were applied per the manufacturers' directions. For the remaining 30,
      enamel was conditioned for twice the time recommended by the manufacturer.
      Buildups were constructed with Filtek Z250 (3M ESPE). Bonded specimens were
      sectioned in sticks and tested to tensile failure. Data were analyzed with 2-way
      ANOVA and Duncan's test at P < .05. The pH of the self-etch solutions and the
      phosphoric acid gel was measured with a pH meter. A correlation coefficient was
      computed to measure the linear association between pH and bond strengths.
      RESULTS: Tyrian SPE and Prime & Bond NT, the adhesives whose acidic conditioners
      yielded the lowest pH, ranked in the highest subset regardless of application
      time. AdheSE and Clearfil SE Bond, which had the highest pH, were the only
      adhesives for which double application time resulted in statistically higher bond
      strengths than the recommended time. When means were pooled for application time,
      Tyrian SPE and Prime & Bond NT resulted in bond strengths that were significantly
      higher than those of the remaining adhesives. AdheSE resulted in statistically
      lower bond strengths than any other adhesive. A significant correlation was found
      between pH and mean bond strengths. CONCLUSION: Doubling the enamel conditioning
      time might increase bond strengths for specific self-etch adhesives.

PMID- 16429702
TI  - Overweight and obesity screening.

PMID- 16429703
TI  - Dimensional accuracy of a new polyether impression material.
AB  - OBJECTIVES: The purpose of this study was to evaluate the dimensional accuracy of
      stone dies produced from standardized impressions with 1 new and 1 conventional
      polyether impression material and a polyvinyl siloxane reference material.
      METHODS AND MATERIALS: Impressions with the polyether materials P2 and Impregum
      and with the polyvinyl siloxane Flexitime were produced at 23 degrees C or 37
      degrees C from a truncated steel cone in cylindrical steel trays giving 4-mm
      impression layer thickness at the prominence line. Stone dies were poured after 1
      or 24 hours of storage at ambient atmosphere. Additional impressions were stored
      at different relative humidity levels (0%, 33%, 50%, 75%, or 100%) for 24 hours
      prior to die pouring. The accuracy of the stone dies was determined as axial
      discrepancy between a steel ring, which fit perfectly on the steel die and the
      occlusal die surface. The base-diameter deviation (deltad) was calculated.
      RESULTS: After 1 hour, a similar increase in deltad was noticed for impression
      materials when dies were poured at impression temperature. Impressions made at 37
      degrees C exhibited significantly higher deltad than at 23 degrees C. Light
      bodied P2 showed the highest deltad increase when dies were poured after 24
      hours. Flexitime showed moderate deltad differences at the 2 pouring times. The
      deltad of dies made from polyether materials decreased significantly with
      increasing humidity, whereas polyvinyl siloxane was not adversely affected.
      CONCLUSION: The dimensional accuracy of P2 is comparable to that of the
      conventional polyether impression material after short-term storage. Polyethers
      may absorb water, significantly compromising die accuracy upon storage at high
      humidity.

PMID- 16429704
TI  - Effects of different retraction medicaments on gingival tissue.
AB  - OBJECTIVE: Exposure of the gingival sulcus and control of hemorrhage are
      prerequisites to the treatment of cervical lesions and improving the quality of
      impressions prior to fabricating indirect restorations. Gingival retraction cords
      saturated with different medicaments are widely used for this purpose. However,
      the long-term effects of the chemicals in gingival tissues are not clear. The
      purpose of this study was to compare the histopathologic effects of 2 different
      retraction solutions in gingival tissue. METHODS AND MATERIALS: In this in vivo
      study, a solution of 10% aluminum chloride and a solution of 15.5% ferric sulfate
      were used as retraction medicament in dogs. The saturated cords were allowed to
      remain in the gingival sulcus of the dogs for 3 minutes. After the removal of the
      cords, gingival biopsies were taken at 30 minutes, 24 hours, 7 days, and 12 days.
      For all specimens, histologic evaluation was performed by light microscopy to
      determine the degree of epithelial loss, alteration of the connective tissue, and
      inflammation. RESULTS: Histopathologic examination of gingival tissue revealed
      that the ferric sulfate solution caused significant changes in gingival tissues
      at the beginning. However, the tissue returned to its normal histologic
      appearance at the end of day 12. CONCLUSION: The results of this study revealed
      that the biologic effects of ferric sulfate solution are more satisfactory than
      aluminum chloride solution. However, both medicaments are reliable and can be
      used in gingival retraction.

PMID- 16429705
TI  - Influence of polishing instruments on the surface texture of resin composites.
AB  - OBJECTIVE: There is a need for an ideal polishing system for resin composite
      restorations. The purpose of this study was to investigate the influence of
      polishing instruments on the surface texture of light-cured resin composites.
      METHODS AND MATERIALS: Four polishing systems-Compomaster (Shofu), Silicone
      Points C Type (Shofu), Super-Snap (Shofu), and Enhance Finishing and Polishing
      System (Dentsply/DeTrey)-were used to polish the flat surface of cylindrical
      blocks made of 3 different resin composites: Beautifil (Shofu), Clearfil AP-X
      (Kuraray Medical), and Lite-Fil II A (Shofu). The average surface roughness (Ra)
      and surface gloss (Gs60 degrees) were determined. Scanning electron microscopic
      observations of the polished specimens were made. The polished samples were
      immersed in a 0.3% acid rhodamine B solution for 1 week, and change in color was
      determined. RESULTS: The multiple-step systems, Enhance and Super-Snap, resulted
      in the best surface finishes. A new single-step point, Compomaster, ranked third
      in surface finish but was significantly better than the older point system,
      Silicone Points C. The color-staining experiments showed that there were no
      significant differences between the Compomaster system and the multiple-step
      systems, which were all significantly better than the older polishing point.
      CONCLUSION: The newly introduced 1-step polishing point has the ability to polish
      resin composites as effectively as multistep polishing systems.

PMID- 16429706
TI  - Ameloblastoma: analysis of 207 cases in a Nigerian teaching hospital.
AB  - OBJECTIVE: The aim of the study was to review all the cases of ameloblastoma seen
      at the Oral and Maxillofacial Surgery Clinic of the Lagos University Teaching
      Hospital, Nigeria, between 1980 and 2003. METHODS AND MATERIALS: In this
      retrospective study, case files and biopsy reports of new cases of ameloblastoma
      covering a 24-year period were retrieved and analyzed for sex, age on
      presentation, histologic type, and site distribution. RESULTS: A total of 207
      cases of ameloblastoma were seen in the given period. One hundred and ninety
      eight (95.7%) were benign, and 9 (4.3%) were malignant. A male-to-female ratio of
      1.1:1 was found. The average ages on presentation for ameloblastoma and
      ameloblastic carcinoma were 31.67 and 46.44 years, respectively. The lesion was
      found to be more common in the premolar-molar region of the mandible. The most
      common histologic type was follicular ameloblastoma (25.1%). Nine (4.3%) cases of
      ameloblastic carcinoma were also reported. CONCLUSIONS: Ameloblastoma with a
      predilection for the posterior mandibular region is relatively common in our
      environment. Sex and site distributions are similar to previous reports in the
      literature.

PMID- 16429708
TI  - Asymmetries in the acquisition of word-initial and word-final consonant clusters.
AB  - Previous work on the acquisition of consonant clusters points to a tendency for
      word-final clusters to be acquired before word-initial clusters (Templin, 1957;
      Lleo & Prinz, 1996; Levelt, Schiller & Levelt, 2000). This paper evaluates
      possible structural, morphological, frequency-based, and articulatory
      explanations for this asymmetry using a picture identification task with 12
      English-speaking two-year-olds. The results show that word-final stop+/s/
      clusters and nasal+/z/ clusters were produced much more accurately than word
      initial /s/+stop clusters and /s/+nasal clusters. Neither structural nor
      frequency factors are able to account for these findings. Further analysis of
      longitudinal spontaneous production data from 2 children aged 1;1-2;6 provides
      little support for the role of morphology in explaining these results. We argue
      that an articulatory account best explains the asymmetries in the production of
      word-initial and word-final clusters.

PMID- 16429707
TI  - Metastasis of breast cancer into the right mandibular condyle.

PMID- 16429709
TI  - Assessing early communicative ability: a cross-reporter cumulative score for the
      MacArthur CDI.
AB  - Thirty middle- to upper middle-class monolingual Dutch speaking families
      consisting of at least a mother and a father completed the Infant Form 'Words and
      Gestures' of the Dutch adaptation of the MacArthur Communicative Development
      Inventory for the same child at 1;1. Considerable inter- and intrafamily
      variation emerged in how two (or three) different reporters who are all
      presumably close to the child assess a particular child's communicative
      abilities. The greater the child's communicative ability, as rated by any one
      reporter, the more differences tended to emerge between reporters. In order to
      take into account multiple reporters' assessments of the same child, we propose
      the use of a Cumulative CDI Score that credits the child with the best score for
      any item on the CDI as checked by any single reporter. We conclude that single
      reporter CDI reports may underestimate the child's communicative knowledge.

PMID- 16429711
TI  - Splitting the notion of 'agent': case-marking in early child Hindi.
AB  - Two construals of agency are evaluated as possible innate biases guiding case
      marking in children. A BROAD construal treats agentive arguments of multi
      participant and single-participant events as being similar. A NARROWER construal
      is restricted to agents of multi-participant events. In Hindi, ergative case
      marking is associated with agentive participants of multi-participant, perfective
      actions. Children relying on a broad or narrow construal of agent are predicted
      to overextend ergative case-marking to agentive participants of transitive
      imperfective actions and/or intransitive actions. Longitudinal data from three
      children acquiring Hindi (1;7 to 3;9) reveal no overextension errors, suggesting
      early sensitivity to distributional patterns in the input.

PMID- 16429710
TI  - A crosslinguistic study of the relationship between grammar and lexical
      development.
AB  - The relationship between grammatical and lexical development was compared in 233
      English and 233 Italian children aged between 1;6 and 2;6, matched for age,
      gender, and vocabulary size on the MacArthur Communicative Development
      Inventories (CDI). Four different measures of Mean Length of Utterance were
      applied to the three longest utterances reported by parents, and to
      corrected/expanded versions representing the 'target' for each utterance.
      Italians had longer MLUs on most measures, but the ratio of actual to target MLUs
      did not differ between languages. Age and vocabulary both contributed significant
      variance to MLU, but the contribution of vocabulary was much larger, suggesting
      that vocabulary size may provide a better basis for crosslinguistic comparisons
      of grammatical development. The relationship between MLU and vocabulary size was
      non-linear in English but linear in Italian, suggesting that grammar 'gets off
      the ground' earlier in a richly inflected language. A possible mechanism to
      account for this difference is discussed.

PMID- 16429712
TI  - Beginning and end in the acquisition of the perfective aspect in Russian.
AB  - The goal of this research is to determine the relevant factors that aid in the
      acquisition of the perfective aspect in Russian. Results confirm the findings of
      previous research, which say that aspect is not learned as a uniform category,
      but rather interrelates with the acquisition of Aktionsarten. This study focuses
      on the factors responsible for the difference in the rate of the acquisition of
      two complementary Aktionsarten in the perfective aspect: telic verbs (verbs
      including a result/goal of the denoted event) and ingressive verbs (verbs
      including the beginning of the event). Since the usage of Aktionsarten strongly
      depends on the surrounding discourse, two experiments that varied in their
      discourse complexity were conducted. One study looked at the production of
      isolated utterances (thirty-nine children aged 3;0 to 6;11) and the other study
      focused on complex texts (fifty-two children aged 3;0 to 6;11). It was found that
      while telics are used independently of discourse context, ingressives depend
      strongly on contextual information. These results suggest that discourse
      complexity and narrative competence define the acquisitional process for
      ingressives, yet are irrelevant in the acquisition of telics.

PMID- 16429713
TI  - A comparison of homonym and novel word learning: the role of phonotactic
      probability and word frequency.
AB  - This study compares homonym learning to novel word learning by three- to four
      year-old children to determine whether homonyms are learned more rapidly or more
      slowly than novel words. In addition, the role of form characteristics in homonym
      learning is examined by manipulating phonotactic probability and word frequency.
      Thirty-two children were exposed to homonyms and novel words in a story with
      visual support and learning was measured in two tasks: referent identification;
      picture naming. Results showed that responses to homonyms were as accurate as
      responses to novel words in the referent identification task. In contrast,
      responses to homonyms were more accurate than responses to novel words in the
      picture-naming task. Furthermore, homonyms composed of common sound sequences
      were named more accurately than those composed of rare sound sequences. The
      influence of word frequency was less straightforward. These results may be
      inconsistent with a one-to-one form-referent bias in word learning.

PMID- 16429714
TI  - Lexical and referential cues to sentence interpretation: an investigation of
      children's interpretations of ambiguous sentences.
AB  - This paper reports on an investigation of children's (aged 3;5-9;8) comprehension
      of sentences containing ambiguity of prepositional phrase (PP) attachment.
      Results from a picture selection study (N = 90) showed that children use verb
      semantics and preposition type to resolve the ambiguity, with older children also
      showing sensitivity to the definiteness of the object NP as a cue to
      interpretation. Study 2 investigated three- and five-year-old children's (N = 47)
      ability to override an instrumental interpretation of ambiguous PPs in order to
      process attributes of the referential scene. The results showed that while five
      year-olds are capable of incorporating aspects of the referential scene into
      their interpretations, three-year-olds are not as successful. Overall, the
      results suggest that children are attuned very early to the lexico-semantic co
      occurrences that have been shown to aid ambiguity resolution in adults, but that
      more diffuse cues to interpretation are used only later in development.

PMID- 16429715
TI  - Age- and ability-related differences in young readers' use of conjunctions.
AB  - Two studies investigating young readers' use of conjunctions are reported. In
      Study One, 145 eight- to ten-year-olds completed one of two narrative cloze tasks
      in which different types of conjunction were deleted. Performance for additive
      conjunctions was not affected by age in this study, but older children were more
      likely to select the target conjunction than were younger children for temporal,
      causal, and adversative terms. Performance was superior in the cloze task in
      which they were given a restricted choice of responses (three vs. seven). In
      Study Two, 35 eight- and nine-year-old good and poor comprehenders completed the
      three-choice cloze task. The poor comprehenders were less likely to select the
      target terms in general. Sentence-level comprehension skills did not account for
      their poor performance. The results indicate that understanding of the semantic
      relations expressed by conjunctions is still developing long after these terms
      are used correctly in children's speech. The findings are discussed in relation
      to the role of conjunctions in text comprehension.

PMID- 16429716
TI  - Crosslinguistic influence in bilingual acquisition: subject omission in learners
      of Inuktitut and English.
AB  - This study investigates subject omission in six English-Inuktitut simultaneous
      bilingual children, aged 1;8-3;9, to examine whether there are cross-language
      influences in their language development. Previous research with other language
      pairs has shown that the morphosyntax of one language can influence the
      development of morphosyntax in the other language. Most of this research has
      focused on Romance-Germanic language combinations using case studies. In this
      study, we examined a language pair (English-Inuktitut) with radically different
      morphosyntactic structures. Analysis of the English-only and Inuktitut-only
      utterances of the children revealed monolingual-like acquisition patterns and
      subject omission rates. The data indicate that these bilingual children possessed
      knowledge of the target languages that was language-specific and that previously
      identified triggers for crosslinguistic influence do not operate universally.

PMID- 16429717
TI  - Yes or no? How young French children combine gestures and speech to agree and
      refuse.
AB  - The aim of the study presented here was to examine variations in the forms and
      functions of agreement and refusal messages--which can be solely gestural, solely
      verbal, or combined gestural and verbal--by thirty children aged 1;4, 2;0, and
      3;0 (ten in each age group) observed at home during an interaction with their
      mother. The results showed that even though verbal forms were the predominant
      ones as a whole, gestural forms were carried over into the linguistic period, and
      for the youngest children, constituted the sole means of agreeing and refusing.
      They also showed that the most frequently expressed function was assertion.

PMID- 16429718
TI  - [The evolution of radical neck dissection and evidence-based medicine].

PMID- 16429719
TI  - [Modalities and nomenclature on surgery for the lymph node metastasis of head and
      neck cancer].

PMID- 16429720
TI  - [Application of supraomohyoid neck dissection in oral squamous cell carcinoma
      with clinically N0 neck].
AB  - OBJECTIVES: The value of supraomohyoid neck dissection used in treating oral
      squamous cell carcinoma was discussed. METHODS: Twenty-seven cN0 patients with
      oral squamous cell carcinoma were entered into the study. Supraomohyoid neck
      dissection was performed to remove the lymphatic tissue of level I, II, and III.
      The operation duration and shoulder function were recorded. RESULTS: The average
      operation duration was (1.6 +/- 0.2) h. Nineteen percent (5/27) of the cN0 neck
      were proved positive pathologically which included two cases in level I and four
      in level II (one case had both level I and II metastases). Shoulder function
      recovered in three months after operation. All patients were followed up from two
      years to four years and none of them had local or neck recurrence. CONCLUSIONS:
      Supraomohyoid neck dissection is a right choice for cN0 patients with oral
      squamous cell carcinoma with its advantages in both curing neck lymphatic
      metastases and preserving neck and shoulder contours and functions.

PMID- 16429721
TI  - [A case of blindness due to infection after sphenoid mucocele operation].

PMID- 16429722
TI  - [Management option for cervical metastases in tongue squamous cell carcinoma with
      clinically N0 neck].
AB  - OBJECTIVE: This study was designed to explore the optimal management option for
      cervical metastases in tongue squamous cell carcinoma (SCC) with clinically N0
      neck in order to avoid excessive or inadequate treatment in clinical practice.
      METHODS: Clinical data of 327 cases of tongue SCC with cN0 neck were
      retrospectively analyzed. Neck control rates affected by different pathoclinical
      parameters were compared. Prognosis analysis and death analysis were also
      performed. RESULTS: Overall 3-year survival was 69.7% (228/327), 3-year survival
      of neck recurrent group and non-recurrent group was 39.1% (25/64) and 77.2%
      (203/263), and 51.5% (51/99) of the death related to neck failure. Overall neck
      control rate was 80.4% (263/327); neck control rate of wait and watch group,
      level I neck dissection, level I + II neck dissection, supraomohyoid neck
      dissection, radical neck dissection, functional neck dissection, was 67.5%
      (27/40), 72.7% (24/33), 60.0% (15/25), 84.9% (45/55), 86.8% (131/151), 84.0%
      (21/25), respectively. Treatment modality and cervical lymph node involvement
      were independent factors for neck control. CONCLUSIONS: Neck control is a key for
      prognosis of tongue SCC with cN0 neck. Supraomohyoid neck dissection is the first
      choice in management of cervical metastases in tongue SCC with cN0 neck, during
      which the suspected involved lymph nodes should be sent for frozen section to
      determine whether comprehensive neck dissection required. Multimodal metastasis
      and/or capsular spread are the indications for postoperative irradiation.

PMID- 16429724
TI  - [A death case of the abrupt irritable digestive ulcer with serious bleeding after
      the laryngectomy].

PMID- 16429723
TI  - [Surgery for the recurrent and persistent lymph node of nasopharyngeal carcinoma
      after radiotherapy].
AB  - OBJECTIVES: To investigate the effect of four types of neck dissections for the
      recurrent and persistent lymph nodes of NPC after radiotherapy. METHODS: The
      clinical data of 88 cases of nasopharyngeal carcinoma with recurrent and
      persistent lymph nodes after radiotherapy were analyzed retrospectively, the 5
      year survival rate, recurrent rate, distant metastatic rate and surgical
      complications were analyzed. The survival rate and recurrent rate of the radical
      neck dissection (RND), modified radical neck dissection (MRND), selective neck
      dissection (SND) and lymph node resection (LNR) were compared. The survival and
      recurrent rate between those with and without postoperative radiotherapy were
      investigated as well. RESULTS: The 5-year survival rate and recurrent rate of
      whole group were 42.8% and 22.7%, respectively. As for the patients with disease
      staged II, III, IV, the 5-year survival rates were 56.7%, 36.1% and 32.4%,
      respectively. The 5-year survival rate of groups of RND, MRND, SND and LMR were
      39.8%, 60.0%, 37.9% and 44.1%, respectively, the differences were insignificant
      (Log Rank = 1.0, P = 0.8011), the recurrent rate of the lymph node among the 4
      groups were insignificant either (chi2 = 0.470, P = 0.493). The 5-year survival
      rates of those with and without postoperative radiotherapy were 39.1% and 45.3%,
      respectively, the differences were insignificant (Log Rank = 0.06, P = 0.8138),
      the recurrent rate of the two groups were insignificant (chi2 = 0.593, P =
      0.441). CONCLUSIONS: The four types of neck dissection were effective and safe to
      control the recurrent and persistent lymph nodes in the neck after radiotherapy,
      as long as choosing patients rationally and gave postoperative radiotherapy if
      necessary.

PMID- 16429725
TI  - [Distribution of cervical lymph node metastasis in patients with cN1 supraglottic
      cancer].
AB  - OBJECTIVE: To study the characteristics of the cervical lymph node metastasis of
      patients with cN1 supraglottic cancer and to elucidate which levels should be
      involved during neck dissection. METHODS: Modified neck dissections or radical
      neck dissections were performed for 108 cases (147 sides) of cN1 supraglottic
      cancer. All the lymph nodes of the samples of 147 operation sides were examined
      pathologically to identify the metastatic levels. RESULTS: Among samples of 108
      cases (147 sides), 126 lymph nodes were metastasis, among which 113 lymph nodes
      were located in levels II and III (89.7%, 113/126), and 123 lymph nodes in levels
      II, III and IV (97.6%, 123/126). The 126 metastatic nodes were distributed in the
      109 levels and 96 of them were in the levels II and III (88.1%, 96/109) and 106
      were in the levels II, III and IV (97.2%, 106/109). Additionally, 45 cases (63
      sides) of the 108 patients were pathologically metastasis (41.7%) and bilateral
      cervical metastasis occurred in 20 cases (18.5%). The cervical recurrent rate was
      7.4% (8/108) and occurred in the levels II, III and IV respectively, during five
      to fourteen years follow-up. CONCLUSION: Levels II, III and IV dissection may be
      reasonable for patients with cN1 supraglottic carcinomas, levels I and V
      dissection may be avoidable when pathological evidence of metastasis in levels I
      and V has not been obtained. Contralateral lymph node dissection at the levels
      II, III and IV should be performed in the case of ipsilateral pN + or
      contralateral metastasis cN1.

PMID- 16429726
TI  - [Pathological feature and management of occult lymphatic metastasis in
      supraglottic carcinoma].
AB  - OBJECTIVE: To study the pathologic feature and management methods of occult
      lymphatic metastasis in patients with supraglottic carcinoma. METHODS: The
      following are criteria of patients selection: (1) Supraglottic squamous cell
      carcinoma; (2) Clinical N0M0; (3) no preoperative radiotherapy and (or)
      chemotherapy. Thirty patients were recruited, male 19 cases, female 11; age: 40 -
      72yr, average 54.8yr; T2 8 cases, T3 18, T4 4 (by UICC 1997). Ipsilateral
      supraomohyoid neck dissections were performed in all cases. Lymph nodes were
      studied histologically according to the levels of dissection. RESULTS: Six of 30
      cases were positive nodes histologically in first operation, 3 were occurrence
      neck metastasis in opposite side during follow ups. Occult metastasis rate was
      20% (6/30) ipsilaterdly and 10% contralaterally. 527 lymph nodes were collected
      in all of 30 patients, average 17.6 nodes in every side neck. Ten positive lymph
      nodes histologically were harvested. The distribution of metastatic lymph nodes
      was 9 in level II, 1 in level III, no in level I. N0 recurrence in larynx and
      (or) at the neck after dissection. Two years survival rates was 86.7% (26/30)
      without tumor. CONCLUSION: Occult metastasis rate of supraglottic carcinoma is as
      high as 30%. The selective lateral neck dissection of level II, III and
      occasionally, level IV was recommended.

PMID- 16429727
TI  - [Efficacy of radical neck dissection for advanced cervical nodal metastases].
AB  - OBJECTIVE: To investigate the efficacy of radical neck dissection (RND) to
      control advanced cervical nodal metastases and analyze the risk factors related
      with cervical recurrence in head and neck cancer. METHODS: One hundred and twelve
      patients with N2, N3 head and neck cancer were treated by RND were
      retrospectively reviewed and the pathological specimen were restudied. RESULTS:
      Five-year cervical recurrence rate of patients with advanced nodal metastases
      after RND is 27.7% (31/112), and 16.5% (13/79), 54.5% (18/33) in N2, N3
      respectively. The overall 3-year, 5-year survival rate of patients with cervical
      recurrence after RND was 16.1% (5/31), 9.7% (3/31) respectively. In a univariate
      chi2 analysis, it was confirmed that the following variables correlated to
      cervical recurrence, i. e., clinical N staging, size of positive neck nodes,
      presence of extracapsular nodal spread and invasion of nonlymphatic structures.
      In a multivariate logistic regression analysis, the most significant risk factor
      for cervical recurrence was the size of positive neck nodes. CONCLUSIONS:
      Cervical recurrence is one of the most common reasons for tumor recurrence of
      head and neck cancer. The size of positive neck nodes is the key risk factor in
      determining the development of cervical recurrence in patients of advanced
      cervical nodal metastases after RND. Patients with presence of extracapsular
      nodal spread and invasion of nonlymphatic structures have high risk of developing
      cervical recurrence.

PMID- 16429728
TI  - [Multiple dentigerous cysts of the jaw: a case report].

PMID- 16429730
TI  - [Distribution of basic fibroblast growth factor in inner ear of guinea pigs
      injected by different drug-approaches].
AB  - OBJECTIVE: To investigate the approach of basic fibroblast growth factor(bFGF)
      entering inner ear, as well as its the protective mechanism to inner ear and
      nerve tissue in pathological situation. METHODS: 125I-bFGF was injected into
      guinea pigs body via the lateral ventricle and muscle under physical situation as
      well as pathological situation. Then the per minute gamma-radioactive in blood,
      liver, thyroid gland, brain, cochlear and perilymph fluid was counted, and the
      distribution and metabolism of bFGF in the inner ear and autoradiography of the
      cochlea were also observed. RESULTS: Gamma-radioactive cpm of blood and liver
      increased significantly, while it did not change in brain, cochlea and perilymph
      after 125I-bFGF intramuscular injections. Gamma-radioactive cpm in blood, liver,
      brain, perilymph and cochlea had increased and autoradiography granules was found
      in the cochlea in 30 min after 125I-bFGF injected into CSF. In brain, perilymph
      and cochlea, a maximal value of gamma-radioactive cpm was obtained between 2 h
      and 4 h, while that in 8 h decreased significantly. Autoradiography granules
      still were seen in 8 h. gamma-radioactive cpm in 12 h was still higher than that
      in control group, but autoradiography granules can't be seen. The result in 24 h
      was similar to that in control group. The time course of cpm in the blood,
      cochlea and perilymph always parallel changed. CONCLUSIONS: bFGF has some
      difficulties in getting across blood-labyrinth barrier (BLB) and blood-brain
      barrier (BBB) under physical and pathological situation, such as acute anoxia,
      aminoglycoside-induced deafness. bFGF can reach inner ear, perilymph fluid, brain
      tissue and blood rapidly when it is injected into CSF and excreted slowly in
      those tissues. Permeability of BBB and BLB to bFGF is similar and has
      orientation.

PMID- 16429729
TI  - [Mutual interaction of vestibular afferent nervous system and vestibular efferent
      nervous system in vestibular compensation].
AB  - OBJECTIVE: To study the mutual interaction of vestibular afferent nervous system
      and vestibular efferent nervous system in vestibular compensation. METHODS: Build
      up animal model of vestibular compensation by destroying single side vestibule of
      wistar rat. In the study the rats were divided into 3 groups: Group A 16 normal
      rats; Group B 15 rats, after 7 days of left vestibular damage; Group C 7 rats 3
      months after left vestibular damage; and Group D 7 rats, after vestibular
      compensation. Electromyography of the rats was recorded and the expression of
      calcitonin gene relative peptide (CGRP), choline acetyltransferase (AChT) and Na
      K-ATPase were investigated in efferent vestibular nervous system. RESULTS:
      Electric potential activity of muscles of injury side decreased while that of the
      opposite side increased. In animals of vestibular compensation electric potential
      of bilateral musculus longus capitis at quiescent stage recovered symmetrically.
      CGRP positive cells of efferent vestibular nervous system increased bilaterally,
      and their activity enhanced, especially obvious at the acute stage. AChT positive
      cells of injury side of efferent vestibular nervous system decreased, but
      reaction degree of two sides enhanced. Reaction degree of the opposite side
      enhanced obviously at the stage of vestibular compensation. Expression of Na-K
      ATPase mRNA of the same side was lower, but vestibular signal of the opposite
      side enhanced, clinically head and neck inclined obliquely by means of medial
      fasciculus of tractus vestibulospinalis. Months later, vestibular signal of the
      same side enhanced, and that of the opposite side enhanced also, clinical
      symptoms improved slightly. At the vestibular compensation stage, expression of
      Na-K-ATPase mRNA of the same side enhanced, and it was same as that of the
      opposite side or much higher, clinically it reached vestibular compensation.
      CONCLUSION: Comprehensive effect of the above results maybe as follows: Efferent
      vestibular nervous system inhibited afferent signal of the opposite vestibule,
      and it modulated excitement of vestibular center of the same side, and it worked
      in the complicated mechanisms of vestibular compensation. CGRP may have
      facilitation function to the vestibular afferent signal of injury side. While Ach
      improved vestibule compensation by means of inhibition of vestibule excitement of
      the healthy side.

PMID- 16429732
TI  - [Infrequent penetrating metallic foreign body in paranasal sinus and encephalic:
      report of one case].

PMID- 16429731
TI  - [Apoptosis and expression of apoptosis-related proteins in experimental different
      denervated guinea-pig facial muscle].
AB  - OBJECTIVE: To study apoptosis and expression of apoptosis-related proteins in
      experimental different denervated guinea-pig facial muscle. METHOD: An
      experimental model was established with guinea pigs by compressing the facial
      nerve 30 second (reinnervated group) and resecting the facial nerve (denervated
      group). TUNEL method and immunohistochemical technique (SABC) were applied to
      detect the apoptosis and expression of apoptosis-related proteins bcl-2 and bax
      from 1st to 8th week after operation. RESULT: Experimentally denervated facial
      muscle revealed consistently increase of DNA fragmentation, average from(34.4 +/-
      4.6)% to (38.2 +/- 10.6)%, from 1st week to 8th week after operation;
      Reinnervated facial muscle showed a temporal increase of DNA fragmentation, and
      then the muscle fiber nuclei revealed decreased DNA fragmentation along with the
      function of facial nerve recovered, latterly normal, average from (32.0 +/-
      8.03)% to (5.6 +/- 3.5)%, from 1st week to 8th week after operation. In
      denervated group, bcl-2 and bax were expressed strongly; in reinnervated group,
      bcl-2 expressed consistently, but bax disappeared latterly along with the
      function of facial nerve recovered. CONCLUSION: Expression of DNA fragmentation
      and apoptosis-related proteins in denervated muscle are general reaction to
      denervation. bcl-2 can prevent early apoptotic muscle fiber to survival until
      reinnervation. It is concluded that proteins control apoptosis may give
      information for possible therapeutic interventions to reduce the rate of muscle
      fiber death in denervated atrophy in absence of effective primary treatment.

PMID- 16429734
TI  - [Effects of hypericin associated with light irradiation on human laryngeal
      squamous cell carcinoma strain Hep-2].
AB  - OBJECTIVE: To study effects of hypericin associated with light irradiation on
      human laryngeal squamous cell carcinoma strain Hep-2. METHODS: Using techniques
      of tumor cells culture in vitro, Hep-2 cells were exposed to different
      concentration hypericin as 0.5, 1.0, 2.0, 3.0, 5.0 microg/ml, then 10 minutes 7.5
      J/cm2 light irradiation was given after an hour. Other groups Hep-2 culture cells
      were also exposed to different concentration hypericin as 5.0, 10.0, 20.0, 25.0
      microg/ml, without light irradiation. In all groups, contrast groups were set up.
      And 48 hours later, growth characteristics of Hep-2 cells were studied by
      morphological observation, fluorescence microscope, MTT assay and flow cytometry.
      RESULTS: In normal contrast group, Hep-2 cells grew intensively and contacted
      with each other. However, cells which were treated with hypericin, combination
      with light irradiation were declined greatly. In higher dose hypericin group,
      necrosis could be found. MTT assay showed that hypericin associated with light
      irradiation inhibited growth of laryngeal cell with dose dependence manner. Flow
      cytometry showed that hypericin with light irradiation could block cell growth at
      G0/G1 phase, inducing apoptosis of laryngeal cell. Under fluorescence microscope,
      some sings of cell apoptosis including coagulation of chromatin, fragmentation of
      nuclei and apoptotic body could be found. CONCLUSION: Human laryngeal squamous
      cell carcinoma strain Hep-2 can be inhibited and induced into apoptosis by
      treated with hypericin combination with light irradiation.

PMID- 16429733
TI  - [Effects of budesonide, desloratadine and dexamethasone on interleukine-4 release
      and expression from human mast cell line].
AB  - OBJECTIVE: Since human mast cell is an important source of cytokines, it is of
      importance to understand the effects of anti-allergic drugs on cytokines
      modulation in mast cells. In the present study, we aimed at observing whether IL
      4 could be released from human mast cell line (HMC-1) after the stimulation of
      PMA + A23187, and the effects of systemic glucocorticosteroid, dexamethasone,
      topical glucocorticosteroid, budesonide and H1 antagonist, desloratadine on IL-4
      release and mRNA expression. METHODS: HMC-1 was stimulated with 25 ng/ml phorbol
      12-myristate 13-acetate (PMA) and 2.5 x 10(-7) mol/L ionomycin (A23187) and
      cultured for 6 hours, 12 hours and 24 hours respectively in the presence or
      absence of 10(-6)-10(-10) mol/L concentrations of test drugs. Culture
      supernatants were collected and the levels of IL-4 were assayed by enzyme-linked
      immunosorbent assays (ELISA). The mRNA expression of IL-4 was measured by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: HMC-1 expressed IL-4 mRNA and the resulting protein production of IL-4
      released after being stimulated with PMA plus A23187. Dexamethasone, budesonide
      and desloratadine had potent inhibitory effect on IL-4 release at any
      concentrations and time points, with significant deference (P < 0.05) compared to
      the control cells. The inhibitory effect did not show time-dependent and
      concentration-dependent manner. Desloratadine and budesonide showed neither up
      regulatory nor down-regulatory effects on IL-4 mRNA expression at the test
      concentrations, however, desloratadine could down-regulate IL-4 mRNA expression.
      CONCLUSIONS: HMC-1 could express and produce IL4 after stimulation.
      Dexamethasone, budesonide and desloratadine all had inhibitory effects on IL-4
      release from HMC-1. In addition, desloratadine could also inhibit the IL-4 mRNA
      expression.

PMID- 16429735
TI  - [Anatomic and spiral computed tomographic study of the genial tubercles for
      genioglossus advancement].
AB  - OBJECTIVE: To study anatomic and computed tomographic measurements of Chinese
      mandibular genial tubercles and to evaluate the correlations between them.
      METHODS: The axial images were taken by spiral CT in 40 adult human skulls with 1
      mm thick section from infraorbital margin to menton. Sagittal plane
      reconstruction was produced through mandibular central line. Then the height and
      width of superior genial tubercles, the distance between menton and inferior
      margin of genial tubercles, the distance between mandibular incisor apex and
      superior margin of superior genial tubercles, the thickness of mandible were
      measured respectively. Thereafter anatomic measurements were taken by the same
      methods as computed tomographic images. The measured value were showed as means
      +/- standard deviation, then paired-t test and correlation analysis was made by
      SPSS 10.0. RESULTS: The genioglossus almost origins from superior genial
      tubercles, geniohyoideus from inferior genial tubercles. The height of superior
      genial tubercles which were measured by anatomy and spiral CT were (5.82 +/-
      0.71) mm and (6.17 +/- 0.71) mm respectively. The width of superior genial
      tubercles were (6.98 +/- 1.35) mm and (7.01 +/- 1.13) mm. The distance between
      menton and inferior margin of superior genial tubercles were (11.08 +/- 2.05) mm
      and (10.41 +/- 1.55) mm. The distance between mandibular incisor apex and
      superior margin of superior genial tubercles for male were (15.57 +/- 1.82) mm
      and (14.34 +/- 2.06)mm, and for female were (9.36 +/- 2.79) mm (8.78 +/- 2.53)
      mm. The thickness of mandibles at genial tubercles were (11.95 +/- 1.59) mm and
      (12.19 +/- 1.64) mm. The distance from menton to superior margin of superior
      genial tubercles were (16.1 +/- 2.30) mm and (15.73 +/- 2.12) mm. The
      correlations between anatomic measurements and spiral CT measurements of the
      above mentioned parameters were significant except for height of superior genial
      tubercles (r = 0.59 - 0.92). CONCLUSION: The anatomic and spiral CT measurements
      of genial tubercles appear to have significant correlations. Preoperative spiral
      CT measurements of genial tubercles could be help for the design of osteotomy in
      genioglossus advancement.

PMID- 16429736
TI  - [Changes in shape of upper airway during titrated mandibular advancement: a
      magnetic resonance imaging study].
AB  - OBJECTIVE: To examine adaptive changes in the shape of the upper airway during
      titrated mandibular advancement. Furthermore, to understand the mechanism of
      mandible-adjustable therapy to improve the ventilation. METHODS: Fourteen non
      apnea participated in the study. A custom-made oral device was used to keep the
      mandible in titrated advancement at 0% (F0), 50% (F50), 75% (F75), 100% (F100) of
      the maximum advancement. Magnetic resonance imaging was used to investigate the
      difference in the shape of upper-airway in these 4 positions. Changes in the
      anteroposterior direction (AP), lateral direction (Lat) and its ratio (AP/Lat)
      were calculated, which were transformed into the percentage of the original ones.
      RESULTS: The dose-dependent decrease of AP/Lat was found when the mandible was
      advanced (P = 0.0001). Lateral change rate in percentage increased by degrees (P
      = 0.0023), while the increase of anteroposterior change rate in percentage showed
      no statistical significance. CONCLUSION: The shape of upper airway tended to be
      less round. The enlargement of upper airway during titrated mandibular
      advancement was mainly the result of enlargement in lateral direction.

PMID- 16429737
TI  - [Quality of life survey in children with obstructive sleep apnea hypopnea
      syndrome before and after operation].
AB  - OBJECTIVE: To evaluate the influence of OSAHS in quality of life (QOL) for
      children and its changes before and after surgery. METHODS: Pediatric OSAHS
      disease-specific quality of life survey (OSA-18) and polysomnography (PSG) were
      used to analysis in 54 cases within 4 weeks before surgery. They were treated by
      tonsillectomy in 8 cases and adenoid tonsillectomy in 32 cases, adenoidectomy
      alone in 14 cases and were followed up in 12 to 18 months post-operation.
      RESULTS: The impact of pediatric OSAHS on QOL was severe in 61.11% patients.
      There were significant statistically correlation between OSA-18 and AHI, LSaO2
      before surgery. After surgery, the total scores of QOL were improved in 75.92%
      cases in general. The domains of sleep disturbance in 88.89% cases, caregiver
      concerns in 74.07% and physical suffering in 70.37% were significantly improved,
      respectively. CONCLUSIONS: Pediatric OSAHS had severely influenced in quality of
      life of children. There are significant correlations between the survey in
      quality of life of pediatric OSAHS (OSA-18) and the objective data in PSG. OSA-18
      can be a valuable measure in clinical diagnosis and treatment follow-up.

PMID- 16429738
TI  - [Experimental research on hearing function affected by inner ear blood supply
      occlusion in the oto-neurosurgery operation].

PMID- 16429739
TI  - [Application clinic of anatomy and multi-slice helical CT three-dimensional
      reconstruction in the sphenopalatine foramen].

PMID- 16429740
TI  - [Analgetic effect of transdermal fentanyl on tonsillectomy].

PMID- 16429741
TI  - [Middle cranial fossa approach surgery of facial nerve decompression].

PMID- 16429742
TI  - [Treatment of serious tracheal and esophagus narrow with nickel-titanium stand].

PMID- 16429743
TI  - [A case of tracheo-esophageal fistula with empyema cause of neck trauma].

PMID- 16429744
TI  - [Haemangioblastoma of sellar region: a case report].

PMID- 16429745
TI  - [Diagnostic and therapeutic application of MRI in otologic disease].

PMID- 16429746
TI  - [Lateral neck dissection: how I do it].

PMID- 16429747
TI  - Swallowing and functional outcome after partial laryngectomy: a literature
      review.
AB  - There is a wide range of partial surgical resections for the treatment of
      laryngeal tumours. In addition to good cure rates, the main aim is to preserve a
      competent and functional larynx. Functional outcomes have proven to have a
      substantial effect on postoperative quality of life and are usually included in
      clinical studies. This article reviews reported functional outcomes after partial
      laryngectomies, particularly when related to swallowing. In the majority of
      patients, reports indicate acceptable feeding without the presence of a permanent
      tracheostomy. However, a wide variety of methods and variables are used to
      describe these functional outcomes, making the comparison of functional outcome
      after different treatment modalities and resections difficult. More objective
      evaluation procedures are needed for swallowing to reveal the exact
      pathophysiology, spontaneous progression and prognostic factors after well
      defined laryngeal resections.

PMID- 16429748
TI  - Ventilation tubes in infants increase the risk of otorrhoea and antibiotic usage.
AB  - 1) PROBLEM/OBJECTIVE: The effect of ventilation tubes on acute otitis related
      symptoms (otorrhoea, earache, and fever) and on antibiotic usage was investigated
      in children with persistent otitis media with effusion, as part of a multicenter,
      randomised, controlled clinical trial. 2) METHODOLOGY: One hundred-eighty-seven
      children were randomly placed into either a watchful waiting group (WW group) (n
      = 94) or a group treated with ventilation tubes (VT group) (n = 93). Both groups
      were followed for 12 months. Data were collected from parental reports and from
      medical files kept by the attending ENT-surgeons. 3) RESULTS: There were
      significant differences in the reported frequency of otorrhoea (but not of
      earache or fever) between both groups during follow-up, i.e. children in the VT
      group had more episodes of otorrhoea than the children in the WW group (p <
      0.003). As a consequence, children in the VT group had been prescribed
      antibiotics more often. 4) CONCLUSIONS: Young children treated with ventilation
      tubes due to persistent otitis media with effusion have a higher risk of
      developing otorrhoea because of the tubes, and they have a higher risk of needing
      treatment with antibiotics.

PMID- 16429749
TI  - Maxillary and temporal fibrous dysplasia: three cases.
AB  - PROBLEMS/OBJECTIVES: Fibrous dysplasia (FD) is a benign, expansile lesion of bone
      with slow progression and unknown origin. The purpose of this report is to make
      physicians aware of the symptoms, methods for differential diagnosis, and
      treatment options. METHODOLOGY: Three cases of monostotic FD are presented; two
      involving the maxillary sinus, and one in temporal bone. CT scans are the
      definitive diagnostic and follow-up method. Surgical approaches to alleviate the
      symptoms, including facial deformity, are described. RESULTS: FD went undiagnosed
      for three years in these patients. All three patients were relieved of the
      symptoms by limited surgery, and remained asymptomatic for up to two years after
      the surgery, with no signs of recurrence. CONCLUSIONS: Practitioners should be
      alert to the possibility of FD, particularly if patients develop narrowing of the
      ear canal, or progressive postauricular or maxillofacial enlargement. Minimal
      surgery to alleviate the symptoms is the treatment of choice.

PMID- 16429751
TI  - Wide localized excision and reconstruction for minor salivary gland tumours.
AB  - BACKGROUND: Insufficient excision is one of the main factors leading to
      recurrence of minor salivary gland tumours. Our aim is to perform large
      resections with immediate reconstruction in order to provide local control, as
      well as to achieve better cosmetic and functional results. METHODS: Four
      consecutive patients suffering from minor salivary gland tumours of the upper
      aerodigestive tract were treated: two had adenoid cystic carcinomas (one of the
      lateral oropharyngeal mucosa, one of the retromolar area); one had a polymorphous
      low-grade carcinoma (at the base of the tongue); and one had mucoepidermoid
      carcinoma (on the floor of the mouth). Two radial forearm free-flaps, a trapezius
      myocutaneous pedicled flap (including an adjacent osseous part of the scapula),
      and a sternocleidomastoid muscular pedicled flap were used, respectively, for
      reconstruction. Additional external radiation was used for three patients (60
      cGy). RESULTS: The postoperative course was uneventful for each patient, and the
      ability to chew and swallow was rapidly restored. Two patients, locally
      controlled, with adenoid cystic carcinomas died: one from brain metastases (four
      years post-surgery), the other with pulmonary metastases (eight-years post
      surgery). One patient is alive with a recurrent tumour of the pterygomaxillary
      fossa (without trismus) sixteen years after the original operation; another
      patient is free of recurrent disease at the base of the tongue but has recently
      undergone surgery, with success, for two pulmonary metastases sixty months after
      the initial surgery. CONCLUSIONS: For minor salivary gland carcinoma of the head
      and neck, large resection with immediate reconstruction affords fast recovery and
      long-lasting locoregional control. Additional radiotherapy is feasible.

PMID- 16429750
TI  - Mucoceles of the sphenoidal sinus: a report of four cases and review of the
      literature.
AB  - Mucoceles of the sphenoidal sinus represent less than 2% of paranasal sinus
      mucoceles. The purpose of this paper is to report our experience in patients with
      mucoceles of the sphenoidal sinus. Four patients with this localization were
      observed in our department from 1994 to 2005. Symptoms included headache, visual
      loss, and rhinorrhea. All patients underwent computed tomography (CT) and
      magnetic resonance imaging (MRI). Surgery was performed using an endonasal
      endoscopic procedure, in one case a navigational system was used. In light of
      these observations and a review of literature, the etiopathogenic
      characteristics, clinical aspects, and therapeutic indications of this
      localization are discussed.

PMID- 16429752
TI  - Brown tumour: presenting symptom of primary hyperparathyroidism.
AB  - The skeletal lesions of primary hyperparathyroidism, including brown tumour, are
      rare nowadays, with the practice of checking serum calcium levels leading to an
      earlier diagnosis of hyperparathyroidism. Clinical, laboratory, radiographic and
      histological investigations can lead to a correct diagnosis. Treatment of brown
      tumour focuses on the hyperparathyroidism, and is usually followed by a
      regression of the brown tumour. The diagnosis of hyperparathyroidism and brown
      tumour should be considered in patients with hypercalcaemia and an osteolytic
      expansive bone lesion. We present a patient where a brown tumour of the mandible
      was the presenting symptom of primary hyperparathyroidism.

PMID- 16429753
TI  - Subcutaneous emphysema and mediastinitis: unusual complications of tonsillectomy.
AB  - INTRODUCTION: Subcutaneous emphysema and mediastinitis are rarely reported
      complications of tonsillectomy. CASE REPORT: We describe two patients who
      developed subcutaneous emphysema, one of them with mediastinitis, within a few
      days after tonsillectomy. The diagnosis was based on the clinical presentation
      and confirmed by computed tomography (CT). For the patient without mediastinitis,
      the emphysema disappeared after a short period of reintubation and administration
      of antibiotics. For the patient with mediastinitis, surgical drainage of a
      cervico-mediastinal purulent collection was necessary to obtain healing.
      DISCUSSION: The events leading to subcutaneous emphysema and mediastinitis have
      not been entirely clarified. They probably include direct introduction of air
      into the neck via either the tonsillar bed or a laryngeal or pharyngeal wound
      caused by intubation. The clinical presentation, treatment and possible
      pathophysiology of subcutaneous emphysema and medisastinits are discussed.
      CONCLUSION: Emphysema and mediastinitis after tonsillectomy occur seldomly. If
      rapidly recognised and appropriately managed, mortality can be avoided.

PMID- 16429754
TI  - A clinical case report of a Schwannoma on the tip of the tongue.
AB  - OBJECTIVES: Schwannomas (neurilemmomas) are benign solitary tumours which arise
      from the Schwann cells of the neural sheath, most often from the VIII cranial
      nerve. Extracranially, 25% of all schwannomas are located in the head and neck.
      Intra-oral development is uncommon and a location in the tongue has been reported
      in individual cases. METHODOLOGY: We present a young patient with a schwannoma in
      the distal right side of the tongue. RESULTS: The tumour had grown slowly
      producing no symptoms. The diagnosis was made on histological examination.
      Surgical enucleation of the mass was uncomplicated and there was no recurrence.
      CONCLUSIONS: We report a further case of a schwannoma of the tongue, highlighting
      the need for this to be considered in the differential diagnosis.

PMID- 16429755
TI  - Endoscopic removal of air gun pellet in the sphenoid sinus.
AB  - THE OBJECTIVE: The presence of an isolated foreign body in the sphenoid sinus is
      a rare finding, and a retained projectile in this sinus is even more uncommon.
      CASE REPORT: The authors report the case of a 15-year-old male that was shot in
      the face with an air gun but was nevertheless able to seek for medical help. The
      anatomical considerations of the gunshot injury are made, and radiological
      assessment of the foreign body is presented. THE RESULT AND CONCLUSION: The
      projectile could be successfully removed with an endoscopic technique, no short
      or long term sequelae occurred.

PMID- 16429756
TI  - The power of social change.

PMID- 16429757
TI  - Pragmatic health promotion in a globalised world: reflections on Bangkok from the
      next generation.

PMID- 16429758
TI  - Implementing empowering health promotion programmes for Aboriginal youth in two
      distinct communities in British Columbia, Canada.

PMID- 16429760
TI  - Benchmarks for social justice: assessing the fairness of academic conference
      participation.

PMID- 16429759
TI  - Social networks' influence on tobacco use among students in Dar es Salaam,
      Tanzania.

PMID- 16429761
TI  - Health for All by the year 2000: a retrospective look at the ambitious public
      health initiative.

PMID- 16429762
TI  - [Model for the systematic classification of outcomes in health promotion and
      prevention].
AB  - Successful demonstration of the effects of health promotion calls for systematic
      documentation and comparison of the outcome of different measures and projects. A
      model has been developed in the form of an outcome categorisation system for this
      purpose and is presented here. The model includes four categories covering the
      intermediate outcomes of health promotion measures, and three categories for
      outcomes at the level of health determinants (conditions necessary for health).
      Each category includes three to four sub-categories, for which examples of
      possible indicators are presented. The model can be applied both in the planning
      and in the evaluation stage of a project. This makes it possible for health
      promotion agencies and institutions responsible for funding and promotion to
      obtain a general overview of the outcome of their work.

PMID- 16429763
TI  - Multisyringe flow injection analysis: state-of-the-art and perspectives.
AB  - In the present paper, the characteristics (apparatus, manifold design, and
      operation mode) of multi-syringe flow injection analysis systems are discussed
      and critically compared to those of flow injection analysis and sequential
      injection systems. Furthermore, a survey of applications proposed until the
      present moment is presented, with special emphasis on implementation of in-line
      sample treatment.

PMID- 16429765
TI  - Flow injection spectrophotometric determination of tetracycline in a
      pharmaceutical preparation by complexation with aluminium(III).
AB  - A rapid flow injection (FI) spectrophotometric procedure for tetracycline
      determination is described. It is based on the injection of a 100 microl sample
      solution containing tetracycline into merged streams of aluminium(III) chloride
      (0.01 mol 1(-1)) and Tris-buffer in the presence of KCl (0.06 mol l(-1)), pH 7.0,
      with the same optimum flow rate of 3.2 ml min(-1). A yellow Al(III)-tetracycline
      complex was monitored at 376 nm. The flow injection system and the experimental
      conditions were optimized by means of the univariate method. The procedure was
      applied to the determination of tetracycline in pharmaceutical preparations with
      a high sampling rate of at least 165 h(-1). A high precision with a relative
      standard deviation was obtained less than 0.72 and 0.30% of 5.0 and 10 microg ml(
      1) (n=11), respectively. The detection limit (3sigma) and the quantification
      limit (10sigma) were 0.07 and 0.72 mg l(-1), respectively. There were no
      interference effects from traditional excipients in the dosage forms when the
      method was applied to pharmaceutical preparations. The matrix effect could be
      reduced by the standard addition method.

PMID- 16429764
TI  - Automated method, based on micro-sequential injection, for the study of enzyme
      kinetics and inhibition.
AB  - A micro-reactor system with continual spectrophotometric detection has been
      operated in Sequential Injection lab-on-valve (SI-LOV) mode and applied to enzyme
      kinetics and inhibition studies, using acetylcholinesterase (AChE) and
      angiotensin-converting enzyme (ACE) as model systems. With the advantages of
      automation, real-time kinetic measurement, and thorough mixing, the SI-LOV micro
      reactor system allows for the monitoring of initial reaction rates and
      determination of reactant concentrations in the reaction mixture, both of which
      are essential for the determination of kinetic constants for enzymes and
      inhibitors. Enzyme, substrate, and inhibitor are precisely metered by the syringe
      pump and delivered to a stirred micro-reactor, followed by a reference scan that
      establishes the baseline for the following reaction rate measurement. Michaelis
      constants (Km) for AChE and ACE were determined to be 0.16 mM and 0.30 mM,
      respectively, which are consistent with literature values. The type of inhibition
      (competitive, uncompetitive, or mixed), the dissociation constants for the
      inhibitors, and the inhibitor dose-response curves were also determined.

PMID- 16429766
TI  - Fluorescence determination of the pesticide asulam by flow injection analysis.
AB  - This paper presents the analytical determination of the pesticide Asulam based on
      its native fluorescence. The method was optimized in either a flow injection
      analysis (FIA) assembly or in batch. The maximum fluorescence intensity was
      observed for basic pH solutions and at a lamda(ex) of 258 nm and a lamda(em) of
      342 nm. The influence of different empirical parameters, such as the pH, the
      presence of surfactants, solvent polarity or solved oxygen amount, was studied.
      The calibration range was fitted with a linear equation from 0.01-3 mg l(-1)
      Asulam and 0.005-15 mg l(-1) Asulam for batch and continuous-flow, respectively.
      The RSD for both procedures was 1.0%. After testing the influence of a large
      series of potential interferents, the method was applied to water samples from
      different locations.

PMID- 16429768
TI  - Chemiluminescent determination of the pesticide bromoxynil by on-line
      photodegradation in a flow-injection system.
AB  - A new, robust and simple method is proposed for the chemiluminescent
      determination of the pesticide Bromoxynil. The empirical procedure is performed
      with the aid of a flow-injection manifold provided with an on-line photo-reactor
      to obtain chemiluminescent photofragments. After a period of 12 s of irradiation
      with an 8 W low-pressure mercury lamp, a chemiluminescent oxidation was performed
      with the system potassium permanganate in a polyphosphoric acid medium. The
      photolysis required a basic medium (KOH 0.014 mol l(-1)) with ethanol (1%) as a
      sensitizer. The method allowed the determination of 134 samples (h-1) of
      Bromoxynil in a wide interval of concentrations, over the range 5 x 10(-3) - 1 mg
      l(-1); the detection limit was 5 x 10(-3) mg l(-1). The RSD (n=24) at 0.25 mg l(
      1) of the pesticide level was 2.3%. The method was applied to a water sample and
      to a formulation.

PMID- 16429767
TI  - Sensitive assay for catecholamines in pharmaceutical samples and blood plasma
      using flow injection chemiluminescence analysis.
AB  - A rapid and sensitive chemiluminescence (CL) method using flow injection analysis
      was described for the determination of three catecholamines: dopamine, adrenaline
      and dobutamine, based on their greatly enhancing effects on the CL reaction of
      luminol-potassium periodate in basic solutions. Under the optimized conditions,
      the calibration graphs relating the increase of CL intensity to the concentration
      of the analytes were linear. The present method allows for the determination of
      dopamine, adrenaline, and dobutamine over the range of 1.0 x 10(-10) - 1.0 x 10(
      7) g/ml. The relative standard deviations for measurements (n=11) of dopamine,
      adrenaline and dobutamine were 2.9, 2.3 and 1.8% when the concentrations of three
      catecholamines were at 1.0 x 10(-9) g/ml, respectively. The detection limits of
      the method were 2.0 x 10(-11) g/ml dopamine, 1.0 x 10(-11) g/ml adrenaline and
      4.0 x 10(-11) g/ml dobutamine. The method was successfully applied to the
      determination of three catecholamines in pharmaceutical samples and blood plasma.

PMID- 16429771
TI  - Sequential flow injection determination of chlorine species using a triiodide
      selective electrode detector.
AB  - A flow injection analysis (FIA) method for the determination of four residual
      chlorine species, namely combined available chlorine (CAC), free available
      chlorine (FAC), total available chlorine (TAC) and chlorite (ClO2-) was developed
      using a flow-through triiodide-selective electrode as a detector. An important
      strategy of speciation studies utilized the kinetic discrimination of reactions
      between the CAC and FAC with Fe2+, which was applied to the speciation of FAC,
      CAC and TAC. The speciation of available chlorine species and chlorite (an
      oxychlorine species) was achieved by using the same set-up, but using flow
      streams of different pH. The effects of the pH of the carrier stream, the flow
      rate and the sample volume were studied. The method exhibited linearity from 2.8
      x 10(-6) to 2.8 x 10(-4) M active chlorine (expressed as OCl-) with a detection
      limit of 1.4 x 10(-6) M. The selectivity of the method was studied by examining
      the minimum pH for the oxidation of iodide by other oxidants, and also by
      assessing the potentiometric selectivity coefficients. The proposed method was
      successfully applied to the determination of chlorine species in tap water, and
      disinfecting formulations where good agreement occurred between the proposed and
      standard methods were found.

PMID- 16429770
TI  - Determination of arsenic species in marine samples by HPLC-ICP-MS.
AB  - Arsenic speciation analysis in marine samples was performed using high
      performance liquid chromatography (HPLC) with ICP-MS detection. The separation of
      eight arsenic species viz. arsenite (As(III)), monomethylarsonic acid (MMA),
      dimethylarsinic acid (DMA), arsenate (As(V)), arsenobetaine, trimethylarsine
      oxide (TMAO), arsenocholine and tetramethylarsonium ion (TeMAs) was achieved on a
      Shiseido Capcell Pak C18 column by using an isocratic eluent (pH 3.0), in which
      condition As(III) and MMA were co-eluted. The entire separation was accomplished
      in 15 min. The detection limits for 8 arsenic species by HPLC/ICP-MS were in the
      range of 0.02 - 0.10 microg L(-1) based on 3sigma of blank response (n=9). The
      precision was calculated to be 3.1-7.3% (RSD) for all eight species. The method
      then successfully applied to several marine samples e.g., oyster, scallop, fish,
      and shrimps. For the extraction of arsenic species from seafood products, the low
      power microwave digestion was employed. The extraction efficiency was in the
      range of 52.9 - 112.3%. Total arsenic concentrations were analyzed by using the
      microwave acid digestion. The total arsenics in the certified reference materials
      (DORM-2 and TORT-2) were analyzed and agreed with the certified values. The
      concentrations of arsenics in marine samples were in the range 6.6 - 35.1 microg
      g(-1).

PMID- 16429769
TI  - An electrochemical cell coupled with disposable screen-printed electrodes for use
      in flow injection analysis.
AB  - An electrochemical cell coupled with disposable screen-printed electrodes (SPEs)
      that is specifically designed for use in flow injection analysis (FIA) is
      described in this study. The cell is made of foldable polyoxymethylene (acetal)
      thick platelets with the bottom portion consisting of a cavity track to drag the
      SPEs in position and the top portion having predrilled T-like holes to arrange
      the Ag/AgCl reference electrode and stainless steel inlet & outlet. An "O ring"
      is suitably fixed on the top of the working electrode to form a thin-layer space
      where the electrochemical reaction can take place. Hydrodynamic characterization
      was validated by using a benchmark hexacyanoferrate redox couple. The results of
      practical analysis of glucose in human plasma clearly demonstrate the
      characteristics and applicability of the proposed wall-jet electrochemical cell
      in FIA.

PMID- 16429772
TI  - Minicolumn field sampling--preconcentration of trace zinc from seawater and its
      laboratory detection by flow injection flame atomic absorption spectrometry.
AB  - A simple field sampling-preconcentration method for zinc determination in
      seawater is described. Seawater was collected in situ by pumping it through a
      minicolumn packed with a chelating resin (Chelite P) connected to a field flow
      preconcentration system (FFPS). These packed minicolumns retain the dissolved
      zinc, and once are loaded with the analyte, they are returned to the laboratory
      where they are sequentially inserted into a flow injection system for on-line
      zinc elution with diluted hydrochloric acid and flame atomic absorption
      spectrometric detection. A factorial design has been used to optimize the FFPS
      and the flow injection elution process. The proposed method has a linear
      calibration range from 0.07 to at least 9.4 microg L(-1) of zinc, with a
      detection limit of 0.02 microg L(-1) and a throughput of 26 samples h(-1).
      Validation was carried out against certified reference water samples. This
      procedure has been successfully applied to the determination of Zn in seawater
      samples from Galicia (Spain).

PMID- 16429773
TI  - Enhanced sensitivity in flow injection analysis using a long pathlength liquid
      waveguide capillary flow cell for spectrophotometric detection.
AB  - Incorporation of a liquid waveguide capillary flow cell into a flow injection
      instrument enhances the sensitivity of flow injection analysis with
      spectrophotometric detection by two orders of magnitude. Nitrite determination at
      nM levels has been used to demonstrate the feasibility of this novel technique
      for trace analysis. Combining the long pathlength spectrophotometry with flow
      injection analysis, this technique has advantages of low detection limit, good
      precision and high sample throughput.

PMID- 16429774
TI  - Miniature liquid flow sensor and feedback control of electroosmotic and pneumatic
      flows for a micro gas analysis system.
AB  - Accurate liquid flow control is important in most chemical analyses. In this
      work, the measurement of liquid flow in microliters per minute was performed, and
      feedback control of the flow rate was examined. The flow sensor was arranged on a
      channel made in a polydimethylsiloxane (PDMS) block. The center of the channel
      was cooled by a miniature Peltier device, and the change in temperature balance
      along the channel formed by the flow was measured by two temperature sensors.
      Using this flow sensor, feedback flow control was examined with two pumping
      methods. One was the electroosmotic flow method, made by applying a high voltage
      (HV) between the reagent and waste reservoirs; the other was the piezo valve
      method, in which a micro-valve-seat was fabricated in a PDMS cavity with a
      silicone diaphragm. The latter was adopted for a micro gas analysis system
      (microGAS) for measuring atmospheric H2S and SO2. The obtained baselines were
      stable, and better limits of detection were obtained.

PMID- 16429775
TI  - An improved method for the flow-injection determination of iodine using the
      luminol chemiluminescence reaction in a reversed micellar medium of
      cetyltrimethylammonium chloride in 1-hexanol-cyclohexane.
AB  - To eliminate the use of chlorinated hydrocarbons, we have improved the method for
      the flow-injection (FI) determination of iodine based on the chemiluminescence
      reaction of iodine with luminol in a chloroform-free reversed micellar medium of
      the surfactant cetyltrimethylammonium chloride (CTAC) using a mixture of 1
      hexanol-cyclohexane as a bulk solvent. The FI procedure used simply involves the
      mixing of an iodine solution in cyclohexane with the chemiluminescent reagent
      solution of luminol in the reversed micellar medium of CTAC in 0.38 M 1-hexanol
      in cyclohexane/water (buffered with sodium carbonate). The optimum conditions for
      the iodine determination were evaluated and a detection limit (DL) of 0.05 ng cm(
      3) iodine was achieved. The calibration graph obtained was linear with a dynamic
      range from the DL to 10 ng cm(-3) iodine. The relative standard deviations (n=5)
      observed at all concentrations within the linear range were less than 2.5%. The
      improved FI method is rapid and equally sensitive like the original one and was
      found to be suitable for the determination of trace iodine.

PMID- 16429776
TI  - Sequential injection analysis with chemiluminescence detection for the
      antioxidative activity against singlet oxygen.
AB  - A sequential injection analysis (SIA) with chemiluminescence (CL) detection was
      developed for the measurement of antioxidative activity against singlet oxygen
      ((1)O2). Lactoperoxidase-hydrogen peroxide-bromide ion system was used for the
      generation of (1)O2. When a 100 mM sodium acetate buffer (pH 4.5) was used as a
      carrier solution, the SIA-CL system could be optimized with respect to the flow
      rate of the carrier, concentration of reagents and their aspiration order. The
      antioxidative activity was expressed as an attenuation of luminol CL due to the
      quenching of (1)O2 by an antioxidant. The relative standard deviations of
      antioxidative activity (n=3) against (1)O2 for within- and between-day analyses
      were < or = 1.6% (20 microM Trolox). The system was successfully applied to the
      assay of antioxidative activities of various antioxidants including vitamin
      supplements at a rate of 10 samples within 15 min. The proposed SIA-CL system was
      rapid and reproducible with minimum consumption of the sample and of reagents,
      and thus was useful for the screening of compounds possessing antioxidative
      activity against (1)O2.

PMID- 16429777
TI  - Repetitive determination of chemical oxygen demand by cyclic flow injection
      analysis using on-line regeneration of consumed permanganate.
AB  - A cyclic flow injection analysis (cyclic FIA) for the repetitive determination of
      chemical oxygen demand (COD) was developed. The acidic KMnO4 method was carried
      out by adopting a single-line circulating flow system. The oxidant (KMnO4)
      consumed by the oxidation of organic substances was regenerated and reused
      repeatedly, resulting in an extreme reduction of hazardous wastes. Only 50 ml of
      the reagent carrier solution containing 0.2 mM KMnO4 and 1 mM HIO4 in 0.8 M H2SO4
      solution was continuously circulated through the system. The KMnO4 could play two
      roles: acting as an oxidant of the organic substances and/or a spectrophotometric
      reagent. The co-existing HIO4 acted as a regenerator of KMnO4, which made it
      possible to recycle the system repeatedly. Under two different digestions (70 and
      130 degrees C), 50 repetitive determinations of standard sodium oxalate (6.5 mg
      COD L(-1)) and D-glucose (7.2 mg COD L(-1)) were skillfully carried out with a
      slightly decreased baseline. The analytical frequency was 30 samples per hour for
      COD determination. The proposed method saved consumption of the used reagents,
      KMnO4 and H2SO4, and thus these wastes were extremely reduced. The obtained COD
      values with the proposed method were co-related with those provided by the manual
      standard method, but were fairly low owing to the insufficient digestion step.

PMID- 16429778
TI  - Electrochemical immunoassay for vitellogenin based on sequential injection using
      antigen-immobilized magnetic microbeads.
AB  - A rapid and sensitive immunoassay for the determination of vitellogenin (Vg) is
      described. The method involves a sequential injection analysis (SIA) system
      equipped with an amperometric detector and a neodymium magnet. Magnetic beads,
      onto which an antigen (Vg) was immobilized, were used as a solid support in an
      immunoassay. The introduction, trapping and release of magnetic beads in an
      immunoreaction cell were controlled by means of the neodymium magnet and by
      adjusting the flow of the carrier solution. The immunoassay was based on an
      indirect competitive immunoreaction of an alkaline phosphatase (ALP) labeled anti
      Vg monoclonal antibody between the fraction of Vg immobilized on the magnetic
      beads and Vg in the sample solution. The immobilization of Vg on the beads
      involved coupling an amino group moiety of Vg with the magnetic beads after
      activation of a carboxylate moiety on the surface of magnetic beads that had been
      coated with a polylactate film. The Vg-immobilized magnetic beads were introduced
      and trapped in the immunoreaction cell equipped with the neodymium magnet; a Vg
      sample solution containing an ALP labeled anti-Vg antibody at a constant
      concentration and a p-aminophenyl phosphate (PAPP) solution were sequentially
      introduced into the immunoreaction cell. The product of the enzyme reaction of
      PAPP with ALP on the antibody, paminophenol, was transported to an amperometric
      detector, the applied voltage of which was set at +0.2 V vs. an Ag/AgCl reference
      electrode. A sigmoid calibration curve was obtained when the logarithm of the
      concentration of Vg was plotted against the peak current of the amperometric
      detector using various concentrations of standard Vg sample solutions (0-500
      ppb). The time required for the analysis is less than 15 min.

PMID- 16429779
TI  - Microbioassay system for an anti-cancer agent test using animal cells on a
      microfluidic gradient mixer.
AB  - We developed a novel microbioassay system equipped with a gradient mixer of two
      solutions, and we applied the microfluidic system to an anti-cancer agent test
      using living animal cells on a microchip. A microchannel for the gradient mixing
      of two solutions and eight other microchannels for cell assay were fabricated on
      a poly(dimethylsiloxane) substrate using a soft-lithography method. The functions
      necessary for this bioassay, i.e., cell culturing, chemical stimulation, cell
      staining, and fluorescence determination, were integrated into the microfluidic
      chip. Eight gradient concentrations of the fluorescein solution, ranging from 1
      to 98 microg/ml, were archived at 0.1 microl/min on a microchip. A stomach cancer
      cell line was cultured, and a cell viability assay was conducted using 5
      Fluorouracil as an anti-cancer agent on the microchip. Cell viability changed
      according to the estimated concentration of the agent solution. With the
      microbioassay system, an anti-cancer agent test was conducted using living cells
      simultaneously in eight individual channels with the gradient concentration of
      the agent on a microchip.

PMID- 16429780
TI  - Electrochemical determination of minoxidil in different pharmaceutical
      formulations by flow injection analysis.
AB  - The electrochemical behavior and amperometric-FIA quantification of minoxidil at
      a glassy carbon electrode is described. The procedure is based on electrochemical
      oxidation at 0.800 V (vs. Ag/AgCl/NaCl(3 M) in a phosphate buffer solution.
      Minoxidil was determined over the range 1 x 10(-7) - 1 x 10(-4) M. Different
      analytical parameters and electrode stability were analyzed to obtain the best
      electrode performance. The optimal conditions were: working potentials, 0.800 V;
      flow rate, 0.74 mL min(-1); and solution pH 7.0. This system allowed a sampling
      rate of 120 samples per hour without any pretreatment. The proposed method was
      used for minoxidil quantification in pharmaceutical preparations with
      satisfactory results. The accuracy of FIA-amperometric method was established by
      a comparison with the conventional UV determination technique using a paired t
      test indicating the absence of systematic errors.

PMID- 16429781
TI  - Flow-injection determination of L-histidine with an immobilized histidine oxidase
      from Brevibacillus borstelensis KAIT-B-022 and chemiluminescence detection.
AB  - A chemiluminometric flow injection analytical system for the quantitation of L
      histidine is described. Histidine oxidase (EC 1.4.3.-) from Brevibacillus
      borstelensis KAIT-B-022 was immobilized on tresylated poly(vinyl alcohol) beads
      and packed into a stainless-steel column. The hydrogen peroxide produced was
      detected chemiluminometrically by a flowthrough sensor containing immobilized
      peroxidase (EC 1.1 1.1.7). The maximum sample throughput was 10 h(-1). The
      calibration graph was linear from 0.05 to 5 mM; the detection limit (signal to
      noise ratio = 3) was 0.01 mM. The activity of immobilized histidine oxidase
      reduced to 65% of the initial value after 350 injections. The system was applied
      to the determination of L-histidine in fish meat, such as salmon, tunny, bonito,
      and mackerel.

PMID- 16429782
TI  - Micro flow injection analysis combined with a separation technique for the
      urinary glucose assay.
AB  - A urinary glucose assay has been investigated, employing a micro flow injection
      analysis (microFIA) combined with a separation technique of glucose from the
      analyte. The adsorption part using activated alumina for the glucose in the
      analyte can be successively integrated onto a microFI chip. The selective
      adsorption-desorption of glucose in the artificial urine can progress on the
      adsorption part. Along with this selective preconcentration of glucose, the
      typical FI peak of glucose can be obtained just by feeding the sample and
      deionized water as an elutant sandwiched with the reagent on the carrier stream.
      The glucose concentration in artificial urine can be quantitatively determined
      with the present microFIA system, while the interference of other components
      coexisting in urine occurs in the case of the conventional FIA system without any
      separation part. The described method serves as a template for improving the
      selectivity for the analyte in the multi-component system.

PMID- 16429783
TI  - Flow injection determination of xanthine oxidase inhibitory activity and its
      application to food samples.
AB  - The enzyme xanthine oxidase (XOD) has been recognized as a key enzyme causing
      oxidative injury to tissues by ischemia-reperfusion. For this reason, XOD
      inhibitor, which effectively suppresses this enzyme, plays an important role in
      the inhibition of many diseases related to reactive oxygen species (ROS). In
      order to screen XOD inhibitors rapidly and conveniently, a novel assay using flow
      injection analysis (FIA) was proposed in the present investigation. To optimize
      the practical FIA system, we studied the effect of the reagent concentrations and
      the flow condition on the enzymatic reaction, and then selected the optimum
      condition as follows: 200-mU/ml XOD concentration, 0.5-mM xanthine concentration,
      0.5-ml/min flow rate, and 2-m mixing coil length. Under this condition, a typical
      XOD inhibitor quercetin was determined in the concentration range 0.1 - 1.5 mM at
      a sampling frequency of 10 samples/h. Using the optimized FIA method, we
      determined the XOD inhibitory activity of some food samples: onions, apples and
      teas, which are the high sources of flavonoids known as the potential XOD
      inhibitors. Among these samples, tea leaves showed the highest activity, the
      second was onions and the lowest was apples. Based on the result of the assay,
      not only quercetin, but also other components in investigated samples,
      contributed to the XOD inhibitory activity.

PMID- 16429784
TI  - Cost-effective flow cell for the determination of malachite green and
      leucomalachite green at a boron-doped diamond thin-film electrode.
AB  - An electrooxidation and a cost-effective flow-based analysis of malachite green
      (MG) and leucomalachite green (LMG) were investigated at a boron-doped diamond
      thin-film (BDD) electrode. Cyclic voltammetry as a function of the pH of the
      supporting electrolyte solution was studied. Comparison experiments were
      performed with a glassy carbon electrode. A well-defined cyclic voltammogram,
      providing the highest peak current, was obtained when using phosphate buffer at
      pH 2. The potential sweep-rate dependence of MG and LMG oxidation (peak currents
      for 1 mM MG and LMG linearly proportional to v 1/2, within the range of 0.01 to
      0.3 V/s) indicates that the oxidation current is a diffusion-controlled process
      on the BDD surface. In addition, hydrodynamic voltammetry and amperometric
      detection using the BDD electrode combined with a flow injection analysis system
      was also studied. A homemade flow cell was used, and the results were compared
      with a commercial flow cell. A detection potential of 0.85 V was selected when
      using a commercial flow cell, at which MG and LMG exhibited the highest signal-to
      background ratios. For the homemade flow cell, a detection potential of 1.1 V was
      chosen because MG and LMG exhibited a steady response. The flow analysis results
      showed linear concentration ranges of 1-100 microM and 4-80 microM for MG and
      LMG, respectively. The detection limit for both compounds was 50 nM.

PMID- 16429785
TI  - Selective and simultaneous determination of phosphate and silicate ions in
      leaching process waters for ceramics glaze raw materials of narutal origin by ion
      exclusion chromatography coupled with UV-detection after postcolumn
      derivatization.
AB  - The selective and simultaneous ion-exclusion chromatography (IEC) with UV
      detection on a weakly acidic cation-exchange resin column in the H+ -form (TSKgel
      Super IC-A/C) was developed and applied for the simultaneous determination of
      phosphate and silicate ions as the water quality parameters required for
      optimizing the water-leaching process for ceramics glaze raw materials of natural
      origin including feldspar, woods-ash, and straw-ash. Phosphate and silicate ions
      in these water-leaching process water samples were separated selectively from the
      coexisting anions such as sulfate, chloride, nitrate and carbonate ions, based on
      the ion-exclusion separation mechanism. They were detected selectively and
      simultaneously by a postcolumn derivatization with molybdenum-yellow using the UV
      detector. Under the optimized separation and detection conditions (eluent, 0-1 mM
      sulfuric acid; reactant, 10 mM sodium molybdate-25 mM sulfuric acid; detector, UV
      at 370 nm; temperature, 45 degrees C), the linearity of calibration was in the
      range 0.1 - 10 ppm for both phosphate and silicate ions, and the detection limits
      at S/N = 3 were 2.58 ppb for silicate ions and 4.75 ppb for phosphate ions. The
      effectiveness of this method was demonstrated in practical applications to the
      water-leaching process for some ceramics glaze raw materials.

PMID- 16429786
TI  - Interferences removal for cadmium determination in samples with complex matrices
      by hydride generation coupled with non-dispersive atomic fluorescence
      spectrometry.
AB  - An intermittent on-line concentration and separation system coupled with HG-AFS
      was developed to eliminate serious interferences from Cu2+, Pb2+ and Zn2+ on the
      determination of cadmium. In the present method, the interferences from common
      coexisting ions, such as Cu2+, Pb2+, Zn2+, Fe3+ and Ni2+, were greatly reduced.
      Under the optimized conditions, a detection limit of 3 pg ml(-1) (3sigma, n=11)
      and a precision of 1.9% RSD for 1 ng ml(-1) of Cd were obtained. The method was
      successfully applied to the determination of cadmium in a series of Chinese
      Geological Reference Materials (SRMs) and GBW01621 ferronickel alloy using simple
      aqueous standard calibration technique. The results obtained were in good
      agreement with the certified values.

PMID- 16429787
TI  - A simple flow injection spectrophotometric procedure for the determination of
      diazepam in pharmaceutical formulation.
AB  - A single-channel flow injection (FI) manifold with spectrophotometric detection
      has been designed and fabricated for diazepam determination. A 100 microl sample
      and/or standard solution containing diazepam was injected into a flowing stream
      of 0.1 mol L(-1) hydrochloric acid with the optimum flow rate of 6.8 mL min(-1).
      As soon as the sample reached the detector, the FI signal as a peak was recorded
      at 360 nm. The optimum conditions for microg amounts of diazepam were achieved. A
      linear calibration graph over the range of 2-110 mg L(-1) diazepam was obtained
      with the regression equation Y = 0.2926X + 0.5896 (r2 = 0.9929). The method was
      very sensitive, since as little as 0.60 mg L(-1) could be detected; very
      reproducible with an RSD of 3.3% (n=11); and very rapid with a sampling rate of
      100 h(-1). The limit of quantitation (10 sigma) was 2.0 mg L(-1). The proposed FI
      procedure has been satisfactorily applied to the quantitation of diazepam in
      commercial pharmaceutical formulations. The obtained results were in excellent
      agreement with those obtained by the conventional spectrophotometric method,
      verified by the student t-test at the 95% confidence level.

PMID- 16429788
TI  - Sequential injection analysis for the simultaneous determination of clavulanic
      acid and amoxicillin in pharmaceuticals using second-order calibration.
AB  - In this paper, we report on a method for quantifying clavulanic acid and
      amoxicillin simultaneously in pharmaceuticals using sequential injection analysis
      (SIA) with a diode-array spectrophotometric detector and multivariate curve
      resolution with alternating least squares (MCR-ALS). We optimized the
      experimental parameters so that the analytical sequence could distinguish the
      concentrations and spectrum profiles of the species of interest with optimum
      resolution quality. After establishing the optimum conditions, we quantified
      clavulanic acid and amoxicillin in four pharmaceuticals. In most cases our
      results were slightly higher than those in the prospectus of the pharmaceutical.
      The relative standard deviations were below 5% for amoxicillin and below 7% for
      clavulanic acid. These results are acceptable because, to prevent degradation due
      to bacteriostatic activity, the concentration of the main reactant is usually
      higher.

PMID- 16429789
TI  - Development of sequential injection-lab-at-valve (SI-LAV) micro-extraction
      instrumentation for the spectrophotometric determination of an anionic
      surfactant.
AB  - The development of instrumentation for sequential injection analysis with a "lab
      at-valve" (SIA-LAV) micro-extraction system is presented. The extractive
      determination of an anionic surfactant using methylene blue was selected as a
      model. Sample, reagents and organic solvent were sequentially aspirated into an
      extraction coil connected to the center of a selection valve, where extraction
      took place by flow reversal. The aqueous and organic phases were separated in a
      LAV unit attached to one port of the valve. The LAV unit situated a fiber-optic
      spectrophotometer to monitor the absorbance change of the extract product in the
      organic phase. The developed SIA-LAV system offers an alternative micro-total
      analysis system for automated micro-extraction.

PMID- 16429790
TI  - Pneumatic flow injection analysis-tandem spectrometer system for iron speciation.
AB  - A pneumatic flow injection-tandem spectrometer system, without a delivery pump
      was used for the speciation of iron. In this system, the suction force of a
      pneumatic nebulizer of a flame absorption spectrometer was used for solution
      delivery through the manifold. The Fe(III) and total Fe concentrations were
      determined using thiocyanate ion in a UV-Vis spectrometer and a FAAS,
      respectively. The Fe(II) was determined by the difference. The calibration curves
      were linear up to 18 microg mL(-1) and 25 microg mL(-1) with detection limits of
      0.09 microg mL(-1) and 0.07 microg mL(-1) for Fe(III) and Fe(II), respectively.
      The mid-range precision and accuracy were <2.5% and +/-3% for the two species,
      respectively, at a sampling rate of 120 h(-1). This system was applied for the
      determination of Fe(III) and Fe(II) in industrial water, natural water and spiked
      samples.

PMID- 16429791
TI  - Determination of starane (fluroxypyr) herbicide using flow injection
      spectrophotometry.
AB  - The starane herbicide was spectrophotometrically determined by the diazotization
      method in a flow injection assembly. Since starane is a substituted pyridyl
      compound the NH2 group at the p-position was exploited for diazotization. Starane
      was diazotized with nitrite and the diazotized product is coupled with beta
      naphthol. The absorbance of the resulting azo dye was measured at 395 nm with a
      molar absorptivity of 1.5 x 10(4) L mol(-1) cm(-1). The calibration graph was
      linear over the range of 0.6 to 10 microg/mL, with a relative standard deviation
      (RSD) of 1.67% and a sampling through put of 60 samples h(-1). The % recovery for
      the determination of starane was found to be 96%. The method was successfully
      applied to the determination of the active ingredient of starane herbicide in its
      formulation as well as in food samples.

PMID- 16429792
TI  - Simple sequential injection analysis systems with a dynamic surface tension
      detector.
AB  - Simple sequential injection analysis systems with DSTD (SIA/DSTD) have been
      developed. One was employed for the study of the effects of the ion contents in
      solutions to the dynamic surface pressure of ionic surfactants. The results from
      the studies show the possibility for an alternative simple fast screening, but
      also a sensitive procedure for water quality determination. Another simple
      SIA/DSTD system has been demonstrated for the quantification of an anionic
      surfactant using a single standard calibration.

PMID- 16429793
TI  - Simple spectrophotometric flow injection system with an in-valve minicolumn for
      enhancement during the determination of chromium(III) using EDTA.
AB  - A simple spectrophotometric flow injection (FI) procedure for the determination
      of Cr(III) using ethylenediaminetetraacetic acid (EDTA) was developed. An FI
      system with a column packed with Amberlite IR-120(H) was employed for sample
      pretreatment. This leads to the possibility of a single standard calibration. A
      linear calibration in a range of 10-27 microg Cr(III) was obtained with a
      detection limit of 1 microg Cr(III) and RSD of 2% (18 microg Cr(III), n=12). The
      proposed procedure was applied for determination of Cr(III) in leachate and
      dietary supplement samples. The results agreed with those obtained by the
      standard methods.

PMID- 16429794
TI  - Sequential injection titration with spectrophotometric detection for the assay of
      acidity in fruit juices.
AB  - A simple sequential injection analysis (SIA) with spectrophotometric detection
      for an assay of acidity in fruit juice was investigated. An alkaline reagent
      (sodium hydroxide), a sample and an indicator (phenolphthalein) were first
      aspirated and stacked as adjacent zones in a holding coil. With flow reversal
      through a reaction coil to the detector, zone penetration occurred, leading to a
      neutralization reaction that caused a decrease in the color intensity of the
      indicator being monitored for absorbance at 552 nm. The effects of various
      parameters were studied. Linear calibration graphs for acidities of 0.2 - 1.0 and
      0.5 - 2.5% w/v citric acid as a standard, with a relative standard deviation of
      1% (acidity of 0.3 - 0.6% w/v as citric acid, n=11) and a sample throughput of 30
      samples h(-1), were achieved. The developed method was validated by a standard
      titrimetric method for assaying the acidity of fruit juice samples.

PMID- 16429795
TI  - Speciation of chromium in seawater by ICP-AES with dual mini-columns containing
      chelating resin.
AB  - A method for the preconcentration and speciation of chromium in seawater was
      developed. On-line preconcentration and determination were carried out by using
      inductively coupled plasma atomic emission spectrometry (ICP-AES) with dual mini
      columns containing a chelating resin. In this system, Cr(III) was collected on
      the first column. The effluent containing residual chromium from the first column
      was collected on the second column after passing through a reduction-switching
      unit, in which the reducing agent was introduced, or not, for the reduction of
      Cr(VI) to Cr(lII). Cr(VI) was determined as the difference between the
      concentration of pre-reduced Cr(VI) and Cr(III) in the effluent from the first
      column. The detection limits for Cr(III) and Cr(VI) were 0.04 and 0.09 microg l(
      1), respectively.

PMID- 16429796
TI  - Flow injection spectrophotometric determination of bromoxynil herbicide by
      diazotization method.
AB  - A flow injection spectrophotometric method is proposed for the determination of
      bromoxynil herbicide. Bromoxynil was hydrolyzed with HCl and the resulting
      product, 3,5-dibromo-4-hydroxyaniline, was diazotized with nitrite and coupled
      with aniline. The absorbance of the azo dye was measured at 500 nm. The
      conditions were optimized for diazotization using FIA. The range of linearity was
      found to be 0.01 to 5 ppm with a molar absorptivity of 1.27 x 10(5) L mol(-1) cm(
      1). The % recovery for the determination of bromoxynil was found to be 91%. The
      sampling frequency was 80 samples per hour for FIA. The method is simple, fast,
      and has been successfully applied to the determination of bromoxynil in
      commercial formulations and food samples.

PMID- 16429797
TI  - Sequential determination of trace amounts of iron and copper in water samples by
      flow injection analysis with catalytic spectrophotometric detection.
AB  - A simple flow injection analysis (FIA) method is described for the sequential
      determination of iron and copper. The detection method for iron and copper is
      based on their catalytic activities in the oxidation reaction of N,N-dimethyl-p
      phenylenediamine (DPD) with hydrogen peroxide. The sequential determination of
      iron and copper can be carried out by injecting two sample plugs into the FIA
      system, sequentially. One injection does not contain triethylenetetramine (TETA),
      and is used for the sum of iron and copper concentration; the other which
      contains TETA is used only for the iron concentration. For iron determination,
      TETA is used as a masking agent of copper. The difference in peak height can be
      used for the calculation of copper concentration. Under the optimal conditions,
      the detection limits (3sigma) of 0.01 and 0.07 microg L(-1) were obtained for
      iron and copper, respectively. The proposed method can be applied to the
      determination of iron and copper in tap water and bottled-drinking mineral water
      samples. Good recoveries of the method, 98-103% for iron and 98-106% for copper,
      were achieved.

PMID- 16429798
TI  - Novel determination system for urea in alcoholic beverages by using an FIA system
      with an acid urease column.
AB  - A novel determination method for urea using an acid urease column-FIA system was
      developed, and the system was applied to the determination of urea in rice wine.
      This novel FIA system was characterized by CO2 detection due to the property of
      acid urease and by a microfluidic gas-diffusion device with the use of an ultra
      thin hollow fiber membrane. A biosensing system fabricated in this study was
      assembled with a double-plunger pump, a sample-injection valve, an immobilized
      acid urease column as a recognition element for the assay of urea, a gas
      diffusion unit, and a flow-type spectrophotometer. The gas-diffusion unit
      consisted of a double-tubing structure in which the outer tubing was made of PTFE
      (i.d. 1.0 mm; o.d. 1.5 mm) and the inner tubing was of porous PTFE (i.d. 0.19 mm;
      o.d. 0.25 mm). Standard urea solutions (20 microl) were measured through
      monitoring variations in the absorbance of a coloring agent solution resulting
      from a pH shift due to carbon dioxide molecules being enzymatically generated. A
      wide and linear relationship was obtained between the concentration of urea (16
      microM - 1.0 mM) and the change in absorbance. This FIA system has great
      advantages that the system did not suffer from ammonia and ethanol in samples.
      This system, armed with a microfluidic gas-diffusion device, was applicable to
      the determination of various substrates of many kinds of decarboxylase, amino
      acid oxidase, and amino-acid oxygenase, producing CO2 and NH3 molecules.

PMID- 16429799
TI  - Determination of trace amounts of cobalt(II) by flow injection-solid phase
      spectrometry (FI-SPS) with 5-Br-PADAB.
AB  - Flow injection-solid phase spectrometry (FI-SPS) has been applied to the
      determination of cobalt(II) in water samples. The complex formed between cobalt
      and 5-Br-PADAB was on-line protonated and concentrated on an AG 50W-X2 cation
      exchanger in a flow-through cell. The increase in absorbance caused by the
      accumulation of the complex in the resin was continuously measured. The
      interference by copper could be effectively eliminated by using EDDP as a masking
      agent. The detection limit was 40 ng dm(-3) with a 4.0 cm3 sample solution.

PMID- 16429800
TI  - Determination of ceftriaxone sodium in pharmaceutical formulations by flow
      injection analysis with acid potassium permanganate chemiluminescence detection.
AB  - Based on the chemiluminescence (CL) emission generated from the oxidation of
      ceftriaxone sodium alkali hydrolysate by potassium permanganate in polyphosphoric
      acid (PPA), a novel determination method for ceftriaxone sodium was developed by
      using a flow-injection technique. The calibration curve appears to be linear in
      the range between 0.05 and 100 microg mL(-1) with a detection limit (3sigma) of
      25 ng mL(-1), and a relative standard deviation (RSD) of 0.6% for eleven
      replicate determinations of 5.0 microg mL(-1) ceftriaxone sodium. The proposed
      method has been successfully utilized for the determination of ceftriaxone sodium
      in pharmaceutical formulations, while the chemiluminescence reaction mechanisms
      were investigated.

PMID- 16429801
TI  - Biosecurity in 121 Danish sow herds.
AB  - Herds are under constant risk of introducing new pathogens from different
      sources. In this article we describe biosecurity practices in Danish sow herds.
      Between December 1, 1999 and February 29, 2000, 121 sow units were interviewed
      regarding biosecurity on the site. The questionnaire contained 62 questions. The
      121 units were situated in three areas with different swine densities. Sow units
      were described by their sizes (units with >110 sows were regarded as large herds)
      and health status (SPF herds or conventional herds). Of the 121 sow herds, 63
      (52%) sold weaners. Most sow units (71%) used delivery facilities for the picking
      up of weaners, but half of these did not have a barrier between the loading area
      and the stable while loading. In 19% of the units, weaners were picked up
      directly from the stable, and in 10% the truck driver had access to the stables.
      Most units required the vehicle to be cleaned (16%) or cleaned and disinfected
      (48%) before the transport; large sites and SPF sites more often required
      stricter biosecurity measures, for example a quarantine period before the
      transport of weaners.

PMID- 16429802
TI  - Disease protection vs animal protection--synergisms and contradictions.
AB  - Health is an important part of animal welfare. This implies that measures for the
      protection against disease will also affect animal protection. In most instances,
      efforts to improve disease protection act synergistically with efforts to promote
      animal protection, and vice versa. In the context of farm animal transport,
      however, infectious disease protection and animal protection may not always be
      mutually beneficial. Examples of contradictions are: Logistic perturbations;
      Current farm animal production is increasingly sensitive to logistic
      perturbations. Control and prevention of epizootic diseases involve extraordinary
      transport precautions that rapidly result in overcrowded stables. Transhumance;
      The practise of transhumance is compromised when control measures are taken to
      prevent spread of epizootic diseases. Travel sickness; Travel sickness is a
      problem particularly in pigs. Starvation before transport prevents vomiting but
      result in hungry animals. Lack of experience; Animals that are kept under
      conditions estranged from situations associated with transport alike are more
      prone to transport induced stress. Flooring; A non-slip flooring is a
      prerequisite for firm footing but demand more careful cleaning and disinfection
      to prevent spread of infectious agents.

PMID- 16429803
TI  - New diseases and increased risk of diseases in companion animals and horses due
      to transport.
AB  - Dogs and horses are transported within the European Union for a number of
      reasons. The transport per se may cause physical problems, exemplified by
      hyperthermia in dogs and pleuropneumonia in horses, and the stress may reactivate
      latent infections such as canine herpesvirus-1 and equine herpesvirus-1.
      Preventive treatments are vital to protect dogs from ticks and mosquitoes
      transmitting their potentially lethal infectious agents, such as Leishmania
      donovani infantum, Babesia canis, Ehrlichia canis, and Dirofilaria immitis.
      However, records show that the travelling dogs are not fully protected since
      cases occur in non-endemic regions. The brown dog tick also poses a risk for
      humans by transmitting Rickettsia conorii causing Mediterranean spotted fever.
      Further, the trade in stray dogs from southern Europe has placed a particular
      focus on the occurrence of vector-borne diseases in the Mediterranean basin. The
      unknown origin of strays also poses a risk for rabies. With respect to horses,
      those transported to southern Europe may be exposed to Theileria equi and Babesia
      caballi, both of which are transmitted by ticks. Horses with antibodies against
      these parasites are not permitted to enter the USA. Additionally, viral diseases
      such as African horse sickness, transmitted by midges, and Borna disease, of the
      mode of transmission is yet unclear, may also pose a risk for horses travelling
      to potentially endemic regions.

PMID- 16429804
TI  - Development phases of long distance transport vehicles for cattle in Finland.
AB  - The development and research work on long distance road trains (transport times
      of 814 hours) was done in three phases: 1991-1993 (1st generation vehicles), 1997
      (second generation vehicles) and 2000-2001 (third generation vehicles). During
      this time, vehicle design, materials and equipments were improved significantly.
      As a result of this developments, cattle can be transported for 8 to 14 hours
      with new, special equipped vehicles without transportation having any significant
      effect on animal welfare, stress level, carcass or meat quality.

PMID- 16429805
TI  - The new European zoonosis legislation--relevant aspects.

PMID- 16429806
TI  - Echinococcus Multilocularis and Trichinella spp. two re-emerging parasites.

PMID- 16429807
TI  - The walrus and the carpenter were walking close at hand.

PMID- 16429808
TI  - Bioterror in a veterinary perspective.

PMID- 16429809
TI  - Emerging viral zoonoses.

PMID- 16429810
TI  - Emerging zoonoses--yesterday, today and tomorrow.

PMID- 16429811
TI  - Prion diseases in man and animals.

PMID- 16429812
TI  - Emerging zoonoses in cats and dogs.

PMID- 16429813
TI  - Rodent and arthropod-borne viral zoonoses in Northern Europe.

PMID- 16429815
TI  - [The future of the form of the profession].

PMID- 16429814
TI  - Food borne zoonoses and Occam's razor.

PMID- 16429816
TI  - [The nursing profession influx].

PMID- 16429817
TI  - [A mirror for nurses].

PMID- 16429818
TI  - [This journal has always been relevant. 100th year of this publication].

PMID- 16429819
TI  - [The nurse as sister].

PMID- 16429820
TI  - [Who? How? What? Who does not ask, remains foolish].

PMID- 16429821
TI  - [Nursing in Germany is a profession for women--a look at nursing in 2006].

PMID- 16429822
TI  - [Regulating from a global perspective].

PMID- 16429823
TI  - Effect of extrusion on trypsin inhibitor activity and nutrient digestibility of
      diets based on fish meal, soybean meal and white flakes.
AB  - The effects of moist extrusion processing of diets containing fish meal (FM) and
      conventional defatted soybean meal (SBM) or untoasted defatted soybean meal
      (white flakes [WF]) on amino acid composition, trypsin inhibitor activity (TIA),
      and apparent total tract digestibility of nutrients were studied. Three diets
      with the nutritional characteristics of feeds for salmonid fish were formulated:
      one control based on FM as protein source and two others where 40% of total amino
      acids from FM were substituted by either SBM or WF. Each diet was fed to mink
      either as an unextruded mixture of the ingredients or as extruded pellets in
      order to determine the effect of extrusion processing. Extrusion did not change
      the amino acid composition of the diets significantly, but reduced the TIA of
      both diets containing soy products by approximately 76%. Intake of the unextruded
      WF diet was only one-third compared with the other diets. The dry matter
      concentration in faeces from mink fed diets containing soy products was
      significantly lower than in mink fed the FM diet. Digestibility of crude protein,
      all amino acids and fat was lower, but starch higher, in the unextruded WF diet
      than in the FM and SBM diets, whereas no significant differences were found among
      the extruded diets. Extrusion of the WF diet increased digestibility of protein
      and all amino acids. The greatest increase in digestibility after extrusion of
      the WF diet was observed for cysteine followed by tryptophan. Extrusion of the FM
      and SBM diets had no significant effect on amino acid digestibility.
      Digestibility of starch was, in general, increased by extrusion. It is concluded
      that the heat treatment involved in typical moist extrusion processing used for
      fish feed may be sufficient to inactivate most of the TIA in unheated soybean
      meal, and to increase digestibility of the protein in WF to approximately the
      same level as found for SBM and FM. Still, extrusion is a lenient process with
      minor effects on nutrient digestibility of diets containing fish meal or toasted
      soybean meal as major protein sources.

PMID- 16429825
TI  - Effect of daily concentrate intake at weaning on performance of Belgian Blue
      double-muscled rearing calves.
AB  - Weaning at a different daily concentrate intake was investigated during a 140-d
      experimental period, using 54 male and 68 female newborn Belgian Blue double
      muscled animals. They were divided into three comparable groups and received milk
      at 10% of their birth weight up to weaning. Concentrate was levelled off at a
      maximum daily intake of 3 kg, while grass hay was freely available. Weaning
      occurred at a daily concentrate intake level (CL) of 0.5, 0.75 and 1.0 kg,
      respectively. Weaning at an increased CL prolonged the milk-feeding period by
      13.1 and 14.6 days, and resulted in a higher pre- and post-weaning growth rate (p
      < 0.05). Daily gain during the entire experimental period averaged 0.84, 0.85 and
      0.88 kg for the respective groups (p = 0.065). Daily concentrate intake was not
      different among groups, with only a small effect of CL on intake around weaning.
      Early weaning resulted in a significant reduction of hay intake (p = 0.032).
      Total daily net energy intake increased slightly with a higher CL at weaning, so
      that energy conversion was slightly improved, amounting to 17.7, 17.6 and 17.4
      MJ/kg gain, respectively. Energy balance during the first week after weaning was
      negative for CL 0.5 kg (-22%), while it was close to 0 for CL 0.75 kg (-2%) or
      positive for CL 1.0 kg. Most effects of CL at weaning were similar for males and
      females, but male calves tended to have a higher intake and a faster growth rate
      than females. It can be concluded that weaning should be delayed until Belgian
      Blue double-muscled calves consume at least 0.75 kg per day or more for reasons
      of welfare, although performance was hardly improved by weaning at a daily
      concentrate intake of more than 0.5 kg per day.

PMID- 16429824
TI  - The influence of ergot-contaminated feed on growth and slaughtering performance,
      nutrient digestibility and carry over of ergot alkaloids in growing-finishing
      pigs.
AB  - Diets containing 0, 1 and 10 g ergot (Claviceps purpurea) per kg, corresponding
      to mean total alkaloid contents of 0.05, 0.60 and 4.66 mg/kg (sums of
      ergometrine, ergotamine, ergocornine, alpha-ergocryptine, ergocristine, ergosine
      and their -inine isomers analysed by a HPLC-method), were each fed ad libitum to
      12 pigs in the BW range of 30-115 kg to study the effect of ergot-contaminated
      feed on growth and slaughtering performance and the carry over of ergot
      alkaloids. Additionally, balance trials were conducted to investigate the
      digestibility of nutrients. Tendencies towards reduced feed intake and BWG were
      observed at a feeding level of 4.66 mg total alkaloids per kg diet. Typical
      symptoms of ergot poisoning were not observed. Heart and spleen weights showed
      significant linear increases. Differences in carcass quality due to dietary
      treatment were not detected. No genuine ergot alkaloids were found in
      physiological samples. The balance trials demonstrated a significantly decreased
      protein digestibility for the most highly supplemented diet.

PMID- 16429826
TI  - Response of performance characteristics and fecal consistency to long-lasting
      dietary supplementation with the probiotic strain Bacillus cereus var. toyoi to
      sows and piglets.
AB  - As part of an interdisciplinary research project, we studied the performance
      response of sows and their litters to the probiotic strain Bacillus cereus var.
      toyoi as well as feces consistency of piglets. Gestating sows (n=26) were
      randomly allotted into two groups. The probiotic B. cereus var. toyoi was
      administered by dietary supplementation to one group of sows and their respective
      litters (probiotic group) whereas the second group (control group) received no
      probiotic supplementation. The duration of the application was nearly 17 weeks
      for sows (day 90 ante partum until day 28 post partum) and six weeks for piglets
      (day 15-56). Piglets were weaned after 28 days. Body weight and feed consumption
      were recorded weekly and fecal consistency of weaned piglets was studied daily.
      B. cereus var. toyoi was recovered from feces of sows and piglets as well as from
      digesta of piglets in the probiotic group, while being absent from all samples of
      control animals. In addition, the probiotic was detected in piglet feces and
      digesta before pre-starter feed was offered, indicating a second route of uptake
      besides diet. Sows of the probiotic group nursed numerically more piglets and
      supported a higher sum of total nursing days of all piglets within each litter
      than control sows (p = 0.04). In turn, body weight (BW) up to day 35 was greater
      for control piglets (p < 0.01), while average daily gain and gain to feed ratio
      (G:F) in weeks six and eight postweaning was higher in the probiotic group (p <
      0.05). The overall G:F of the total postweaning period was 680 g/kg and 628 g/kg
      in the probiotic group and control group, respectively (p = 0.009). During the
      trial a high prevalence of liquid feces with its maximum in the second week after
      weaning was observed. Probiotic supplementation led to a reduction in the
      incidence of liquid feces and postweaning diarrhea by 38% and 59%, respectively
      (p < 0.001).

PMID- 16429827
TI  - Effects of feeding antibiotic-free creep feed supplemented with oligofructose,
      probiotics or synbiotics to suckling piglets increases the preweaning weight gain
      and composition of intestinal microbiota.
AB  - The objective of this study was to determine whether feeding an antibiotic-free
      creep feed supplemented with either oligofructose, probiotics or synbiotics to
      suckling piglets influences growth performance, the gut microflora, gut
      morphology and hematological traits at weaning. Twenty sows with 10 piglets each
      were randomly assigned to one of four treatments. The treatments consisted of a
      control (antibiotic-free) diet, 0.2% oligofructose (OF), 0.3% probiotics or 0.5%
      synbiotics (mixture of 0.2% OF+0.3% probiotics). Piglets were offered the diet ad
      libitum from 7 d after birth until one day after weaning (21 d of age). At the
      day after weaning, blood samples were collected from the jugular vein to
      determine the immune response. Digesta samples of the ileum and colon were
      collected to determine the microbial composition. Tissue segments from the
      duodenum and ileum were collected for morphometric measurements of the small
      intestine. The average daily weight gain was significantly higher for piglets fed
      the OF or synbiotics diet compared with the pigs fed the control diet. The
      hematological traits (the concentration of lymphocytes and neutrophils in whole
      blood) were not affected by the diet. Piglets fed the OF, probiotics or
      synbiotics diet had a significantly decreased number of total coliform bacteria
      in the colon. Feeding OF, probiotics or synbiotics significantly increased the
      population of bifidobacteria in the ileum compared to the control. In the colon,
      the probiotics and synbiotics diet significantly increased the number of
      bifidobacteria compared with the control diet. The results of this experiment
      showed that supplementation of oligofructose or synbiotics to an antibiotic-free
      creep feed during the preweaning period affected gut microbial population and
      performance of piglets.

PMID- 16429828
TI  - Conjugated linoleic acid can prevent tumor necrosis factor gene expression by
      inhibiting nuclear factor binding activity in peripheral blood mononuclear cells
      from weaned pigs challenged with lipopolysaccharide.
AB  - Twenty-four weanling barrows were fed corn-soybean diets supplemented with 2%
      conjugated linolenic acid (CLA) or soybean oil. On day 14 and 21, pigs were
      injected intraperitoneally with lipopolysaccharide (LPS) or sterile saline.
      Plasma samples were collected 2h after injection. Peripheral blood mononuclear
      cells (PBMC) were also collected on day 21, 2 h after injection to determine
      tumor necrosis factor-alpha (TNF-alpha) production and its mRNA expression. The
      results indicate that dietary CLA inhibited the production of TNF-alpha by pig
      PBMC both at the protein and mRNA expression level. In a second experiment, PBMC,
      collected from a healthy pig, were incubated with either c9,t11-CLA or t10,c12
      CLA, or without CLA and stimulated with LPS. Both CLA isomers inhibited LPS
      stimulated TNF-alpha production and expression, which may be partially due to
      inhibition of the binding activity of nuclear factor-kappaB. The t10,c12 isomer
      was more effective than the c9,t11-CLA isomer in reducing TNF-alpha levels and
      nuclear factor-kappaB activation.

PMID- 16429829
TI  - Effect of Ligustrum lucidum and Schisandra chinensis on the egg production,
      antioxidant status and immunity of laying hens during heat stress.
AB  - The experiment was conducted to evaluate the effect of two plants belonging to
      Chinese herbal medicines, Ligustrum lucidum (LL) and Schisandra chinensis (SC),
      on the laying performance, antioxidant status and immunity of hens during heat
      stress. The results showed that diets supplement with 1% of either LL or SC had
      beneficial effects on egg production and FCR of hens during heat stress (p <
      0.05), compared with the control group. Either LL or SC significantly reduced
      malondialdehyde (MDA) concentration of heart, liver, sera and egg yolk. In
      addition, glutathione reductase (GR) activity of tissues and sera of the birds
      was significantly elevated by supplementation LL or SC. Furthermore, LL or SC
      supplementation significantly elevated lymphoblastogenese of the birds and the
      antibody values against Newcastle disease virus (NDV). The results suggest that
      diets supplement with 1% of either LL or SC may enhance egg production, immune
      function, and antioxidant status of hens during heat stress.

PMID- 16429830
TI  - Long term feeding of Bt-corn--a ten-generation study with quails.
AB  - A ten-generation experiment with growing and laying quails were carried out to
      test diets with 40 (starter) or 50% (grower, layer) isogenic or transgenic (Bt
      176) corn. Feeding of diets containing genetically-modified corn did not
      significantly influence health and performance of quails nor did it affect DNA
      transfer and quality of meat and eggs of quails compared with the isogenic
      counterpart.

PMID- 16429831
TI  - [Tomorrow's pharmaceutical dosage forms].

PMID- 16429832
TI  - [Evolution of manufacturing conditions and facilities in the pharmaceutical
      industry].

PMID- 16429833
TI  - [The preparations for inhalation in history (XIXth-XXth century)].

PMID- 16429834
TI  - Ginkgo biloba medicines and food supplements on the Belgian market: a comparative
      study.
AB  - Medicines and food supplements based on the dry extract of the leaves of Ginkgo
      biloba L. were evaluated by determination of the content of total flavonoids,
      rutin and terpene lactones by means of liquid chromatography. All examined
      medicines complied with the fixed requirements whereas all food supplements
      deviated from 1 or more of the criteria. It could also be demonstrated that some
      products contained extracts to which rutin was added.

PMID- 16429835
TI  - Urinary liver-type fatty acid-binding protein levels for differential diagnosis
      of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and
      effect of low-density lipoprotein apheresis.
AB  - AIMS: Focal glomerulosclerosis (FGS) and minor glomerular abnormalities are
      kidney diseases characterized by massive proteinuria. Urinary liver-type fatty
      acid-binding protein (L-FABP), an intracellular carrier protein of free fatty
      acids, is expressed in proximal tubules of the human kidney. Patients with FGS
      show significant improvement with low-density lipoprotein (LDL) apheresis. The
      aim of the present study was to determine whether urinary L-FABP levels differ
      between patients with FGS and those with minor glomerular abnormalities and
      whether levels are altered by LDL apheresis. PATIENTS AND METHODS: There were 24
      patients with minor glomerular abnormalities (nephrotic stage, n = 14, remission
      stage, n = 10), 17 patients with FGS, and 20 healthy age-matched subjects were
      included in the present study. Urinary L-FABP levels were measured by enzyme
      linked immunosorbent assay and compared. All patients with minor glomerular
      abnormalities at the nephrotic stage received prednisolone for 6 months, and all
      FGS patients received some form of immunosuppression therapy with prednisolone,
      cyclophosphamide or mizoribine for 12 months. LDL apheresis was performed in
      eight FGS patients with drug-resistant nephrotic syndrome. RESULTS: Urinary L
      FABP levels were significantly higher in the 17 FGS patients (82.0 +/- 44.4
      microg/g.Cr) than in the 24 patients with minor glomerular abnormalities (10.2 +/
      8.4 microg/g.Cr) (p < 0.01) and in the 20 healthy subjects (7.4 +/- 4.2
      microg/g.Cr) (p < 0.01). Urinary L-FABP levels differed little between nephrotic
      stage and remission stage in patients with minor glomerular abnormalities.
      Urinary L-FABP levels were significantly higher in the eight drug-resistant FGS
      patients (122.6 +/- 78.4 microg/g.Cr) than in the nine drug-sensitive FGS
      patients (45.9 +/- 32.0 microg/g.Cr). Urinary L-FABP levels did not correlate
      with levels of other clinical markers including serum creatinine, urinary
      protein, and urinary N-acetyl-beta-D- glucosaminidase. In the eight drug
      resistant FGS patients, LDL-apheresis significantly reduced urinary protein
      excretion (p < 0.01) and urinary L-FABP levels (p < 0.01). CONCLUSIONS: Urinary L
      FABP may be a useful diagnostic indicator for differentiation between FGS and
      minor glomerular abnormalities. LDL apheresis may be effective in ameliorating
      tubulointerstitial lesions associated with FGS.

PMID- 16429836
TI  - Intravenous pulse cyclophosphamide therapy in focal segmental glomerulosclerosis.
AB  - AIMS: We herein report the results of intravenous pulse cyclophosphamide (IVCP)
      therapy of 5 patients with steroid-resistant focal segmental glomerulosclerosis
      (FSGS). All patients had been treated with oral and intravenous pulse
      methylprednisolone and failed to respond to steroids from onset and were
      considered as primary steroid-resistant. Before starting IVCP, all patients were
      also treated with other immunosuppressive drugs with or without steroids, but
      none of them responded to such therapies and no patient had any NPSH2 gene
      mutations. METHODS: IVCP was given monthly at a dose of 500 mg/m2 for 6 months.
      At the end of 6 months, IVCP was discontinued in case there was no response.
      Otherwise, IVCP was continued for every 2 months. Oral prednisone was given
      concurrently at 60 mg/m2 daily for 6 weeks and then 40 mg/m2 on alternate days
      for 4 weeks. Prednisone was then tapered to 10 mg/m2 alternate days and continued
      during the therapy period. RESULTS: Only 1 of these patients achieved remission
      after IVCP while 4 patients showed no response to IVCP. 2 patients who did not
      achieve remission progressed to end-stage renal disease (ESRD) and 2 others who
      had not been treated with cyclosporine before underwent cyclosporine therapy.
      None of our patients has suffered from adverse effects of IVCP. CONCLUSION: We
      found that IVCP had a limited beneficial effect in treatment of steroid-resistant
      FSGS and it may be suggested that IVCP can be tried to treat steroid-resistant
      patients, also for patients with primary steroid resistance and those who do not
      respond to other immunosuppressive therapies.

PMID- 16429837
TI  - Low urine pH is associated with reduced indinavir crystalluria in indinavir
      treated HIV-infected individuals.
AB  - Indinavir is a potent HIV-1 protease inhibitor included in current antiretroviral
      therapeutic regimens. It is associated with renal and urological complications
      ascribed to indinavir crystalluria. We have previously reported that indinavir
      crystalluria is frequently observed soon after initiation of therapy. In a cohort
      of 54 asymptomatic indinavir-naive HIV-1-infected individuals during their first
      year of treatment with indinavir, approximately 25% of urinalyses (U/A) contained
      indinavir crystals. Because the determinants of the crystalluria are unknown, we
      examined the relationship between urine specific gravity (SG) and pH, singly and
      in combination, and indinavir crystalluria in these subjects. A total of 579 U/A
      were obtained from the study subjects at their scheduled monthly outpatient
      medical assessments. The frequency of indinavir crystalluria was lower in U/A
      with lower pH, irrespective of the SG. Conversely, U/A with high pH (> or = 6.0)
      had a higher frequency of indinavir crystalluria, which was further influenced by
      the urine SG. As a result, nearly half of the U/A (46.7%) with high pH (> or =
      6.0) and intermediate-high SG (> or = 1.015) contained indinavir crystals. In
      conclusion, the frequency of indinavir crystalluria in asymptomatic HIV-1
      infected individuals during their first year of treatment with indinavir was
      markedly influenced by the urine pH and SG. Our findings suggest that low urine
      pH may have a protective effect against indinavir crystalluria across the entire
      range of urine SG.

PMID- 16429838
TI  - Conservative treatment of renal angiomyolipomas in patients with tuberous
      sclerosis.
AB  - AIMS: Renal angiomyolipoma (AML) associated with tuberous sclerosis (TS) presents
      a treatment dilemma due to multifocal tumors with a potential for significant
      growth and subsequent hemorrhage. We reviewed the literature and our experience
      with AML and TS patients to determine the long-term behavior of these lesions.
      MATERIALS AND METHODS: We reviewed 8 patients (16 renal units) with bilateral
      renal AMLs and comorbid TS. We evaluated their renal function, renal imaging, and
      clinical course. Patients were followed for a mean of 11.5 years (range 3.5 - 21
      years). RESULTS: The records of 8 patients (7 females, 1 male) with a mean age of
      33.1 years (range 21 - 54) were evaluated. The mean serum creatinine of these
      patients at the time of diagnosis was 0.75 mg/dl (range 0.4 - 1.1). Mean serum
      creatinine at last follow-up was 0.83 mg/dl (range 0.6 - 1.3). The average size
      of the largest lesion was 13.9 cm (range: 0.5 - 28). Of the 8 patients, 6
      received treatment during the course of their disease, including arterial
      embolization of 7 renal units in 5 symptomatic patients (2 patients needed 2
      embolizations). Partial nephrectomy was performed on 2 renal units in 2 patients,
      and a total nephrectomy was performed in 1971 on another patient. Currently, all
      8 patients have stable renal function; 4 patients are asymptomatic with regards
      to their lesions, while the other 4 patients report transient flank pain
      adequately controlled with oral analgesics (2 patients with propoxyphene plus
      acetaminophen 100/650 mg PO t.i.d. p.r.n., the other 2 patients with ibuprofen
      600 mg PO p.r.n.). None of the patients experienced life-threatening hemorrhage
      or required dialysis. CONCLUSIONS: Our study and a review of the literature have
      not revealed an obvious or quantitative risk of morbidity or mortality from renal
      hemorrhage directly related to AMLs of any specific size in TS patients. Due to
      multiple lesions and distortion of anatomy it can be difficult to distinguish
      individual lesions for preemptive treatment in asymptomatic patients. If size
      criteria alone are used, multiple treatments will be required over the course of
      the patient's life. Also, preemptive treatment exposes patients to iatrogenic
      morbidity. Consideration should be given to medical management of AMLs in TS
      patients with asymptomatic, slowly enlarging tumors that maintain features of an
      AML. Embolization, partial nephrectomy, or other ablative treatments (i.e.
      cryotherapy and RFA) can be reserved for symptomatic patients.

PMID- 16429840
TI  - Choice of replacement solution and anticoagulant in continuous venovenous
      hemofiltration.
AB  - BACKGROUND: Several types of replacement fluid and methods of anticoagulation
      have been employed for continuous renal replacement therapy, but there is no
      consensus on a preferred approach. We evaluated the indications for the selection
      of replacement fluid and anticoagulant among critically ill patients receiving
      continuous venovenous hemofiltration (CVVH) and assessed the effect of the
      selection on the efficacy of anticoagulation and complications. METHODS: We
      retrospectively studied 29 consecutive patients who received CVVH in the Medical
      Intensive Care Unit at Massachusetts General Hospital. There were 3 types of
      replacement solution available, an isotonic citrate solution which was also used
      for regional anticoagulation of the extracorporeal circuit, and bicarbonate and
      lactate solutions which were used with low-dose heparin or no anticoagulant.
      Blood flow rate was set at 120 ml/min when citrate replacement fluid was used and
      at 200 ml/min with bicarbonate or lactate. The replacement fluid was administered
      proximal to the hemofilter at a constant rate of 1,600 ml/h. RESULTS: There were
      22 patients who received citrate replacement fluid which was mainly chosen for
      the purpose of anticoagulation in the setting of contraindications to heparin. 12
      patients received bicarbonate, predominantly when citrate was considered
      contraindicated due to liver failure or high-anion gap metabolic acidosis, and 2
      received lactate; 8 of these 14 patients were anticoagulated with heparin and 6
      were managed without anticoagulation. There were 44 filters used in the patients
      receiving citrate with a median filter life of 42.0 (interquartile range 22.2 -
      70.7) hours. Only 8 of the 44 filters were lost due to clotting. Heparin was used
      for anticoagulation of 17 filters and no anticoagulation was used in the case of
      15 filters, resulting in a median filter life of 43.0 (13.5 - 75.0) and 12.0 (4.0
      - 33.0) hours, respectively. Clinically significant bleeding occurred in 2
      patients, 1 receiving citrate and another receiving heparin. No patient had
      evidence for citrate toxicity, metabolic alkalosis or hypernatremia. 14 (48.3%)
      patients survived. CONCLUSIONS: The use of regional citrate anticoagulation of
      the CVVH circuit appears advantageous in patients with increased risk of bleeding
      and bicarbonate-based replacement fluid seems desirable in patients with lactic
      acidosis due to shock and/or severe liver failure. Tailoring the type of
      replacement fluid and method of anticoagulation to the individual patient leads
      to long filter lives, excellent metabolic control and minimal complications.

PMID- 16429839
TI  - Incidence and factors predictive of acute renal failure in patients with advanced
      liver cirrhosis.
AB  - BACKGROUND: Acute renal failure (ARF) is a life-threatening entity that
      frequently complicates advanced liver disease. This study documents a number of
      factors that may predispose to or precipitate ARF and influence outcomes in
      patients with advanced liver disease. Comparisons are also made between subgroups
      of patients with viral and alcohol-induced liver cirrhosis in those with ARF.
      PATIENTS AND METHODS: We conducted a retrospective chart review over one year of
      127 consecutive hospital admissions in 82 patients who were diagnosed with
      advanced liver cirrhosis (Child-Pugh Class C) in a tertiary care center. A
      diagnosis of ARF was made in 29 admissions and another 98 admissions not
      complicated by ARF served as controls. This study evaluated different etiologies
      of ARF and developed a database which included clinical features, biochemical
      parameters, the etiology of cirrhosis, possible predisposing factors, and
      precipitating events. Version II of the Acute Physiology and Chronic Health
      Physiology Scoring system (APACHE II) was applied to predict short-term hospital
      mortality rates. RESULTS: ARF occurred in 29 admissions over the one-year study
      period (23%). The mean age of these patients was 56.8 +/- 12.0 years, and 73%
      were men. The patients with ARF had significant hyponatremia and higher levels of
      serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), and white cell counts on admission than the controls. Patients who
      developed ARF were more likely to have had infection, especially septicemia, and
      gastrointestinal (GI) bleeding. Mortality rate in the patients with ARF was much
      higher than in those patients without ARF (72% vs. 13%, p < 0.001). The patients
      with viral cirrhosis and ARF were found to have higher leukocyte counts, serum
      bilirubin levels, and more frequent incidence of infection, septicemia and GI
      bleeding compared to the patients with alcoholic liver cirrhosis and ARF. Those
      with viral hepatitis were also significantly older and had more frequent
      incidence of ascites, but had lower levels of gamma-glutamyl transpeptidase and
      less frequent incidence of encephalopathy. CONCLUSIONS: The risk of ARF is
      significantly increased in patients with advanced liver cirrhosis presenting with
      marked hyperbilirubinemia, hyponatremia, elevated liver enzymes, infection, and
      GI bleeding. The presence of ARF leads to higher mortality rates in both viral
      and alcohol-induced liver cirrhosis.

PMID- 16429841
TI  - Timely transfer of peritoneal dialysis patients to hemodialysis improves survival
      rates.
AB  - AIMS: The two main renal replacement therapies (RRT)--hemodialysis (HD) and
      peritoneal dialysis (PD)--have been considered to be antagonistic in most
      published studies on the clinical outcomes of dialysis patients. Recently, it has
      been suggested that the complementary use of both modalities as an integrated
      care (IC) strategy might improve the survival rate of end-stage renal disease
      patients. The aim of this study was to estimate the final clinical outcome of PD
      patients when they transfer to HD because of complications related to PD.
      MATERIALS AND METHODS: We retrospectively analyzed data from the following
      patients that started RRT during the last 10 years: 33 PD patients (IC group; age
      55 +/- 15 years, mean +/- SD) who transferred to HD, 134 PD patients (PD group,
      age 64 +/- 11 years) who remained in PD, and 132 HD patients (HD group, age 48 +/
      16 years) who started and continued in HD. The main reasons for the transfer to
      HD were relapsed peritonitis and loss of ultrafiltration, while various comorbid
      risk factors were adjusted by Cox hazards regression model (age, presence of
      diabetes or/and cardiovascular disease, serum hemoglobin and albumin levels, as
      well as the modality per se). RESULTS: 3- and 5-year survival rates for the IC,
      PD and HD groups were 97% and 81%, 54% and 28%, and 92% and 83%, respectively.
      The 5-year survival rate was significantly higher in IC patients than in PD
      patients (p < 0.00001) but, was not different from that in HD patients.
      CONCLUSIONS: Our results show that the IC of dialysis patients undergoing RRT
      improves the survival of patients on PD if they are transferred to HD upon the
      appearance of PD related complications.

PMID- 16429842
TI  - Rapidly progressive glomerulonephritis in a patient with Chlamydia pneumoniae
      infection: a possibility of superantigenic mechanism of its pathogenesis.
AB  - Herein we describe a case of a patient with rapidly progressive
      glomerulonephritis after Chlamydia pneumoniae infection. An 88-year-old woman who
      had had C. pneumoniae infection two months previously was admitted to our
      hospital with complaints of dyspnea and generalized edema. Laboratory tests
      revealed acute renal failure, polyclonal hypergammaglobulinemia, highly increased
      level of C-reactive protein, and hematoproteinuria. A renal biopsy revealed
      mesangial and endocapillary proliferative glomerulonephritis with crescents. She
      responded to high-dose steroids, cyclophosphamide, minocycline, and plasma
      exchange treatment with the remission of oliguric renal failure. The percentage
      of the subset of CD3+ TCR+ Vbeta11+ cells markedly increased to 9.6% (normal
      range: < 1.04%) at the onset of the disease and decreased to 0.1% after the
      treatment. These clinicopathological features were similar to those of
      superantigen-associated glomerulonephritis after methicillin-resistant
      Staphylococcus aureus infection. We suggest that the superantigenic mechanism is
      one of the possible pathomechanisms of this glomerulonephritis.

PMID- 16429843
TI  - Successful treatment of hepatitis B virus-associated membranous nephropathy with
      lamivudine.
AB  - We present a case of chronic hepatitis B with membranous nephropathy, that was
      improved by lamivudine treatment. A 37-year-old man was admitted to our hospital
      for the evaluation of proteinuria. He was diagnosed as having chronic
      glomerulonephritis associated with chronic hepatitis B. Histopathological
      findings of the renal biopsy specimen indicated membranous nephropathy. He
      suffered from nephrotic syndrome associated with leg edema, which was parallel to
      the exacerbation of hepatitis. Lamivudine was started for the treatment of
      hepatitis, which caused the disappearance of serum hepatitis B virus DNA and the
      normalization of ALT level in 4 weeks. Additionally, proteinuria disappeared 120
      weeks after the treatment was started. Lamivudine treatment may remit HBV
      associated nephropathy.

PMID- 16429844
TI  - A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in
      a Japanese family with Gitelman syndrome.
AB  - Gitelman syndrome is an inherited renal disorder characterized by impaired NaCl
      reabsorption in the distal convoluted tubule leading to hypokalemia,
      hypomagnesemia and normocalcemic hypocalciuria. It has been shown that this
      syndrome results from mutations in the gene encoding the thiazide-sensitive
      sodium chloride cotransporter (TSC). We performed the mutational analysis in the
      TSC gene of a 30-year-old Japanese woman with Gitelman syndrome and found two
      mutations at adjacent spots in both alleles. One was a frame shift mutation which
      generated stop codon at position 671, the other was a single nucleotide mutation,
      which resulted in an aminoacid substitution at position 672, Met to Ile. Her 52
      year-old mother and two daughters had neither hypokalemia nor hypomagnesemia.
      However, her mother and her 8-year-old daughter had the Met672Ile mutation as
      heterozygotes. Her 4-year-old daughter had the same frame shift mutation as her
      mother, a heterozygotic mutation. These results suggest that Gitelman syndrome
      requires 2 compound heterozygotic mutations and the coexistence of the large
      deletion in the C-terminal domain with Met672Ile substitution of the TSC could
      impair the transporter activity underling the hypokalemia and hypomagnesemia in
      this patient.

PMID- 16429845
TI  - Cerebral venous thrombosis in adult nephrotic syndrome due to systemic
      amyloidosis.
AB  - Although venous thrombosis is one of the common complications in nephrotic
      patients, cerebral venous thrombosis (CVT) is rarely reported. CVT is so
      difficult to be detected by conventional diagnostic methods that it is sometimes
      overlooked despite its potential severity. We report a 79-year-old female with
      nephrotic syndrome due to systemic amyloidosis who suddenly altered mental status
      during her hospitalization. The underlying etiology had been not identified by
      physical examinations, various laboratory data, and repeated computed tomography,
      and finally she died. The post-mortem examination showed a massive thrombus
      impacted in intracranial left-sided transverse and sigmoid sinus. This case
      suggests that CVT can occur in a nephrotic patient who presents unexplained
      neurological signs and symptoms, which might not be detected only through
      conventional diagnostic tests.

PMID- 16429846
TI  - Reversible hypocalcemic heart failure with T wave alternans and increased QTc
      dispersion in a patient with chronic renal failure after parathyroidectomy.
AB  - Despite the crucial role of calcium in myocardial contractility, hypocalcemia has
      very rarely been reported as a reversible cause of heart failure. In this
      article, we describe a case of a 51-year-old woman with advanced stages of
      chronic renal failure after parathyroidectomy who exhibited congestive heart
      failure, severe hypocalcemia, hypomagnesemia and hypokalemia. Severe hypocalcemia
      resulted from discontinuation of taking calcium supplements after
      parathyroidectomy and from reduced 1.25(OH)2D3 synthesis by damaged kidneys. The
      patient presented with reduced left ventricular ejection fraction (EF) and ECG
      abnormalities (T wave alternans and increased QTc dispersion), both of which
      improved after correction of serum calcium levels. Her serum levels of total
      calcium corrected for serum albumin, but not serum levels of magnesium or
      potassium, positively and negatively correlated with EF and QTc dispersion,
      respectively. In the present case, both heart failure and the ECG abnormalities
      are directly associated with hypocalcemia.

PMID- 16429847
TI  - Vena cava superior syndrome developing in a dialysis patient with antithrombin
      III deficiency following temporary catheterization.
AB  - Despite being widely reported in patients with neoplasms, vena cava superior
      (VCS) syndrome linked to thrombosis is a major catheter complication that can be
      encountered during the use of the hemodialysis catheter. Antithrombin III (AT
      III), responsible for a large part of thrombin inactivation capacity in plasma,
      is the most powerful inhibitor of the thrombosis process. This report describes a
      case of VCS syndrome developing two weeks following the extraction of a right
      sided subclavian catheter in a patient transferred from peritoneal dialysis to
      hemodialysis for one week due to leakage. The patient presented complaining of
      swelling and pain in the right arm. At Doppler examination, total thrombosis was
      observed in the subclavian and internal jugular vein. At advanced examinations
      due to lack of response to heparin and clinical worsening, VCS and AT-III
      deficiency were determined. Following thrombolytic therapy with streptokinase, AT
      III levels were raised by the administration of plasma, and clinical and
      radiological stabilization was established by continuing heparin and continuous
      oral anticoagulant therapy.

PMID- 16429848
TI  - Changes of neutrophil function during the interdialytic period.

PMID- 16429849
TI  - Magnesium deficiency and diabetes mellitus.

PMID- 16429850
TI  - An evaluation of tomography, cephalometrics and casts in the treatment of
      temporomandibular joint disturbance.

PMID- 16429851
TI  - Orthodontic treatment need and the dental aesthetic index.
AB  - The Dental Aesthetic (DAI) was devised as a measure of dental appearance and
      based on lay opinions as opposed to professional assessments of need. The DAI is
      calculated from the weighted scores of ten occlusal variables. These same
      variables have been used in other malocclusion indices intended to measure
      morphological deviations from normality. It is, therefore, important to ask if
      the DAI might be used to screen both deviations of dental appearance and
      deviations of occlusion from accepted norms. The original DAI design was based on
      analysis data from permanent dentitions. However, a large percentage of
      orthodontic assessments are carried out in the mixed dentition. Therefore, the
      present study includes a sample of mixed dentitions to test the effectiveness of
      the DAI in this group. The DAI was tested against the subjective assessments of
      severity made by orthodontists. Sensitivity and negative predictive power were
      high. Performance in the mixed dentition group was slightly lower than the
      permanent dentition group. It is concluded that while the DAI is not sufficiently
      reliable for assessment of treatment need in the individual, its sensitivity and
      negative predictive power might provide a useful screening mechanism which
      reflects both the concerns of patients regarding appearance and the general
      treatment recommendations of orthodontists. Testing on much larger samples is now
      required.

PMID- 16429852
TI  - The bond strength of orthodontic resins to porcelain.
AB  - Orthodontic brackets were bonded to one of two porcelain surfaces using a self
      cured or one of two light-activated orthodontic bonding resins. The porcelain
      surfaces were either glazed (control) or deglazed (experimental) by being
      subjected to either 1.23% APF for 4 minutes or roughened with a Busch silent
      wheel. The bonds were tested to failure in shear mode on a universal mechanical
      testing machine. For one porcelain, there was no significant difference in the
      mean bond strengths between the control and the APF-treated surface, but for the
      second porcelain the mean bond strength was significantly greater when the
      surface was de-glazed by abrasion. It is considered that the mean bond strengths
      may be inadequate to withstand manipulations associated with routine orthodontic
      therapy.

PMID- 16429853
TI  - Shear bond strength of a mechanically retained ceramic bracket.
AB  - The failure under shear loading of mechanically retained ceramic brackets bonded
      to enamel was investigated. One light-activated dual-cure and two no-mix self
      cure adhesives were compared to all Adhesive Pre-coated bracket (APC). The
      results indicated that the ceramic bracket bonded with the light-activated dual
      cure adhesive had a significantly higher mean shear bond strength than the other
      adhesive systems. All adhesive systems usually failed cohesively with adhesive
      remaining attached to the bracket and enamel surfaces. There was no significant
      difference in failure site. There was a significant difference in the amount of
      adhesive remaining attached to the enamel surface. The light-activated dual-cure
      adhesive and Adhesive Pre-coated brackets failed in 50% and 80% of instances
      respectively, with less than 10% of the adhesive remaining attached to the enamel
      surface. Self-cure adhesives failed usually with 10-90% of the adhesive remaining
      attached to the enamel surface. There were no instances of enamel damage. Three
      cases of bracket fracture occurred, one of these being associated with the
      highest recorded bond strength.

PMID- 16429854
TI  - The Don Spring Memorial Oration--Part II: early management of the developing
      Class III malocclusion.
AB  - It was apparent from Dr Turley's presentation that many cases, previously thought
      to be untreatable by conventional orthodontic means, can be managed with a high
      degree of success using the techniques described. It is hoped that this overview
      of management of the developing Class III malocclusion will provide a rationale,
      a means and a reason for all of us to feel comfortable in treating these
      interesting and sometimes difficult cases.

PMID- 16429855
TI  - Comparison of body height and mandibular length between Caucasian and Japanese
      children.
AB  - This study compared pubertal growth of Japanese males and females with that of
      Caucasian children matched by age and gender. Total body height and mandibular
      length were compared between the two groups. Total body height showed that
      Caucasian males were taller than Japanese males from the ages of 10 to 15 years
      (p< 0.01-0.05). The annual maximum growth of Caucasian females peaked at the age
      of twelve, but Japanese females had a "spurtless" growth pattern, peaking one
      year earlier than Caucasian females. Total mandibular length, calculated at the
      age of 10, was about 3 mm greater in Japanese males and 5 mm greater in Japanese
      females than in Caucasians. At the age 15, the mandibles of Japanese males and
      females were about 7 mm and 9 mm longer than those of Caucasians, respectively.
      Adolescent mandibular growth spurt occurred, on the average, at the age of 13 in
      both Caucasian and Japanese males. Both female groups showed mandibular growth
      peaks at the age of 12.

PMID- 16429856
TI  - The retention phase of treatment: retention--still the stepchild.

PMID- 16429857
TI  - Expert systems in orthodontic clinical diagnosis.
AB  - Computer-aided diagnosis of orthodontic anomalies is of particular interest in
      the screening of potential patients. General practitioners and public dental
      health workers would find considerable benefit in a reliable automated system
      capable of reflecting the clinical assessments of orthodontists. This study
      investigates the application of an expert system (Xpert Rule) to the assessment
      of treatment need using thirteen traits of malocclusion to construct a knowledge
      base. Decision trees were generated using a pruning option available with the
      expert system. The results of the study are encouraging and suggest that an
      expert system is able to generate a useful clinical screening device. Further
      modification of the knowledge base is required to provide a broader range of case
      types, particularly those of less common occurrence. It is also suggested that
      the random aggregation of cases is not the most effective means of developing a
      knowledge base.

PMID- 16429858
TI  - A complex Class II case with crowding and missing teeth.
AB  - Frankel appliance treatment was used from the age of 9 years 3 months to 10 years
      7 months, which is 16 months overall. At 12 years 2 months, region. At 14 years 5
      months, fixed appliances were placed for a period of 16 months. A positioner was
      used from 14 years 8 months until 16 years 3 months, which is an 18 month period.

PMID- 16429859
TI  - Manpower Survey 1991.

PMID- 16429860
TI  - Computers and the orthodontist.
AB  - Dentofacial Planner Plus (DFP) is a computerised cephalometric program that
      enables rapid and accurate analysis of a cephalogram to aid in treatment
      planning. In addition, a video image of a patient's profile can be linked to the
      digitised cephalogram. Manipulation of the tracing will produce corresponding
      changes in the video image. Simulations of orthodontic treatment or orthognathic
      surgery changes are therefore possible. This becomes a valuable aid in treatment
      planning, communication with the oral surgeon and patient education.

PMID- 16429861
TI  - The story of a toothbrush.

PMID- 16429862
TI  - Three professors. A crucial coincidence.

PMID- 16429863
TI  - Personality traits in adolescence and satisfaction with orthodontic treatment in
      young adulthood.
AB  - OBJECTIVE: This study aimed to determine whether personality traits are
      associated with satisfaction with orthodontic treatment by age 26. METHODS: A
      prospective observational cohort study was conducted with 1,037 individuals, one
      third of whom had received orthodontic treatment by age 26. A comprehensive
      personality assessment was conducted at age 18 using the multidimensional
      personality questionnaire. At age 26, orthodontic outcome was rated as either
      'Excellent', 'Pretty good', 'Fair' or 'Poor'. RESULTS: Those who were less
      satisfied (rating their treatment outcome as 'Fair' or 'Poor') scored lower on
      the personality traits of control and social closeness, and higher on stress
      reactivity. Individuals with low scores on social closeness were twice as likely
      (Odds ratio: 2.07) to be less satisfied with their orthodontic result.
      CONCLUSIONS: Individuals who are impulsive, stress-reactive or socially isolated
      are more likely to be disappointed with their orthodontic outcome. Pretreatment
      knowledge about certain aspects of personality might be useful to practising
      orthodontists.

PMID- 16429864
TI  - Factors influencing the non-surgical eruption of palatally impacted canines.
AB  - BACKGROUND: Many palatally impacted canines in children do not require surgical
      exposure prior to the start of orthodontic treatment. They erupt in mid-alveolar
      positions providing excess space is made for them in the arch. The time required
      for an impacted tooth to emerge under these conditions is highly variable. AIM:
      To determine the factors influencing the time required for a palatally impacted
      canine to spontaneously disimpact following orthodontic treatment to create
      excess space in the arch. METHOD: Thirty palatally impacted canines, which
      emerged following orthodontic treatment to open excess space in the arch, were
      used. The impacted teeth were present in 28 children. No canines were surgically
      exposed. The positions of the impacted canines before treatment, the mesiodistal
      widths and rotations of the adjacent and contralateral lateral incisors, age and
      gender of the subjects, subjects' dental ages, presence of either incisor or
      premolar hypodontia, number of subjects with bilaterally impacted canines, and
      number of siblings with impacted canines were recorded. Canines that erupted in
      less than nine months of treatment were compared with canines that required more
      than nine months of treatment. The canines were grouped by severity of impaction
      (sectors II - IV) and compared. RESULTS: There were significantly more severe
      (sector IV) impactions in the long duration group compared with the short
      duration group. Significantly more cases of incisor-premolar hypodontia were
      found in the short duration group. Canines impacted in sector IV emerged after 21
      months of treatment and canines in sectors II and III emerged after eight months
      of treatment. Lateral incisors adjacent to the impacted teeth were rotated
      mesiolabially to a greater extent in the sector IV group compared with lateral
      incisors in the sector II group. Differences in rotation of the adjacent and
      contralateral lateral incisors were significantly less in the sector II group
      compared with the lateral incisors in the sector III and IV groups. CONCLUSIONS:
      The sector of impaction was the best guide to the duration of treatment prior to
      emergence.

PMID- 16429865
TI  - Force systems yielded by different designs of T-loop.
AB  - OBJECTIVES: To determine the mechanical characteristics of beta-titanium T-loops
      with and without helices, with 0 and 180 degree gable bends and constructed from
      0.017 inch x 0.025 inch and 0.019 inch x 0.025 inch wire. METHODS: Forty beta
      titanium T-loops were centrally positioned in a universal testing machine. The
      horizontal force and the moment/force ratios during activation were recorded at 1
      mm intervals, up to a maximum of 7 mm. The data were analysed with analysis of
      variance complemented by the Tukey test for multiple comparisons. RESULTS: The
      results demonstrated that the transverse section of the wire had the greatest
      effect on the horizontal force produced by the loops. Significantly lower levels
      of horizontal force were obtained with loops made with the smaller 0.017 inch x
      0.025 inch wire. Loops with gable bends yielded high moment/force ratios, whereas
      loops without gable bends had low moment/force ratios. In general, T-loops with
      helices yielded lower magnitudes of horizontal force and moment/force ratios than
      plain T-loops. CONCLUSIONS: The horizontal forces and moment/force ratios
      generated by plain T-loops with 180 degree gable bends yielded more adequate
      force systems. Incorporation of helices in the design of T-loops seems to be
      unnecessary.

PMID- 16429866
TI  - Mandibular arch changes following nonextraction treatment.
AB  - OBJECTIVE: To evaluate mandibular tooth position changes following treatment with
      a lip bumper and fixed appliance. Specifically, we aimed to determine how space
      was obtained to align crowded lower incisors. METHODS: Thirty-four consecutively
      treated children with a mean age of 10.6 years (SD: 1.14 years) were selected
      from a specialist orthodontic practice in Eire. All subjects were treated with a
      lip bumper followed by a fixed appliance. The positions and angulations of the
      lower first molars and most proclined lower incisor were measured on the
      pretreatment and post-treatment lateral cephalometric radiographs and study
      models with a reflex metrograph. The changes were also compared with published
      growth data. RESULTS: After lip bumper and fixed appliance treatment the
      mandibular arch depth decreased (Mean difference: 1.2 mm; p < 0.01) and the
      mandibular intermolar width increased (Mean difference: 1.73mm; p < 0.01). The
      mandibular molars moved mesially (Mean difference: 2.14 mm; p < 0.01 and tipped
      distally (Mean difference: 4.36 degrees; p < 0.01). There were no significant
      differences between the pre- and post-treatment positions or angulations of the
      mandibular incisors. Compared to published growth data the arch depth decreased
      less, the intermolar width increased more and the mandibular molars were
      uprighted. There was no difference in the positions of the mandibular incisors in
      the treated group compared with published growth data. CONCLUSIONS: The main
      effects of nonextraction treatment with a lip bumper followed by fixed appliance
      treatment were to maintain the leeway space, expand the mandibular arch and
      'upright' the lower molars. The treatment had no effect on the position of the
      lower incisors.

PMID- 16429867
TI  - Physical properties of human premolar cementum: hardness and elasticity.
AB  - AIMS: To determine if the cementum on the maxillary right and left first
      premolars has identical physical properties. METHODS: Ten normal maxillary first
      premolar teeth, extracted from five orthodontic patients with a mean age of 14.0
      years, were used. The teeth had not been subjected to an orthodontic force. The
      hardness and elastic modulus of the cementum were measured on the buccal and
      lingual surfaces of the roots at three locations: cervical third, middle third
      and apical third. RESULTS: There were no significant side-to-side differences in
      cementum hardness (Mean side-to-side difference: 0.0063 GPa; SD: 0.0279; p =
      0.525) or elastic modulus (Mean side-to-side difference: -0.027 GPa; SD: 0.111; p
      = 0.814). The hardness and elastic modulus of the cementum decreased from
      cervical to apical regions on both root surfaces. CONCLUSIONS: Similar physical
      properties of the cementum on the maxillary right and left first premolars
      suggest that intra-arch comparisons can be used to investigate root resorption
      caused by orthodontic forces.

PMID- 16429868
TI  - SmartClip versus conventional twin brackets for initial alignment: is there a
      difference?
AB  - OBJECTIVE: To compare the effectiveness of SmartClip brackets and conventional
      twin brackets for initial alignment of the lower arch. METHODS: Fifty-eight
      patients participated in this prospective trial. The patients were assigned
      alternately to either a group treated with SmartClip MBT prescription brackets or
      a group treated with conventional MBT twin brackets. Lower anterior irregularity
      was measured at the start of treatment, 10 weeks later at the first archwire
      change and 20 weeks after the start of treatment at the second archwire change.
      RESULTS: There was no difference in irregularity at the start of treatment. At 10
      weeks subjects treated with conventional brackets had a lower irregularity index
      than subjects treated with SmartClip brackets (Mean difference: 0.7 mm; p =
      0.005). After 20 weeks there were no statistically significant differences in
      irregularity between the two groups (Mean difference: 0 mm; p = 0.82).
      CONCLUSION: The SmartClip bracket was no more effective at reducing irregularity
      during the initial stage of treatment than a conventional twin bracket ligated
      with elastomeric modules or stainless steel ligatures.

PMID- 16429870
TI  - Treatment protocol for unilateral cleft lip and palate patients: questioned by
      two case reports.
AB  - BACKGROUND: The types and severity of clefts as well as palatal development and
      growth in children with repaired cleft lip and palate deformities can vary
      greatly. Independent of the technique used surgery produces scar tissue, which
      restricts palatal growth so that by the second decade many patients have an
      underdeveloped maxilla. Experience has shown that the maxillary retrognathism
      found in many cleft patients is not amenable to nonsurgical correction. Few long
      term studies have evaluated the procedures, sequencing and timing of the
      treatment methods found to give the best results. This lack of reliable
      information means there is a serious gap in our ability to assess the value of
      different treatment modalities. AIMS AND METHODS: From the viewpoint of
      orthodontics, this article describes the treatment protocol used by the cleft lip
      and palate team at the University Hospitals of the KU Leuven. The present
      treatment protocol is illustrated and questioned by two cases. The roles of
      prediction of facial growth and distraction osteogenesis are discussed.

PMID- 16429869
TI  - Maxillary molar intrusion with micro-implant anchorage (MIA).
AB  - BACKGROUND: Intrusion of the maxillary molars is difficult to accomplish using
      traditional methods of anchorage. AIMS: To describe methods of maxillary molar
      intrusion with the aid of micro-implants. METHODS: Micro-implants provide stable
      intra-oral anchorage and enable the maxillary molars to be intruded without the
      usual side effects. Three adult patients are presented showing how micro-implants
      can be used to intrude the maxillary molars. In the first patient micro-implants
      were placed in the alveolar process between the second premolar and first molar,
      in the second patient micro-implants were placed in the palatal alveolar process
      between the first and second molars, and in the third patient a micro-implant was
      placed in the palate paramedially. A transpalatal bar was used to prevent bucco-
      or linguoversion of the molars during intrusion. CONCLUSIONS: The maxillary
      molars can be intruded with intra-oral anchorage derived from microscrew
      implants.

PMID- 16429871
TI  - Forces that shape our profession.

PMID- 16429872
TI  - Levels of t-PA and PAI-2 in gingival crevicular fluid during orthodontic tooth
      movement in adults.

PMID- 16429873
TI  - The place of function in modern orthodontics.

PMID- 16429874
TI  - What are the three most important reasons for orthodontic treatment? Are they
      aesthetics, aesthetics and aesthetics?

PMID- 16429875
TI  - Facial aesthetics and the divine proportion: a comparison of surgical and non
      surgical class II treatment.
AB  - OBJECTIVE: This study was designed to compare selected divine or golden
      proportions in Class II division 1 patients treated either during the growth
      phase with an activator and fixed appliances or after the completion of growth
      with fixed appliances and orthognathic surgery; and to determine the associations
      between divine facial proportions and perceived facial attractiveness. METHODS:
      The material consisted of subjects with Class II division 1 malocclusions treated
      either with upper and lower fixed appliances and orthognathic surgery or with
      activators followed by fixed appliances. There were 23 females and 9 males in the
      surgical group (Mean age: 23.5 years; SD: 9.6 years) and 17 females and 11 males
      in the non-surgical group (Mean age: 10.8 years; SD: 1.1 years). The divine
      relationships of the subjects were assessed on pre- and post-treatment lateral
      cephalometric radiographs, and on lateral and frontal facial photographs. In
      addition, the attractiveness of the subjects was scored by a panel of judges
      using a visual analogue scale. Facial aesthetic scores were then correlated with
      the presence of particular divine facial proportions. RESULTS: On average, few
      ratios fitted the divine proportion, either before or after treatment in either
      treatment group. There was, however, significant individual variation in the
      presence or otherwise of these divine proportions, as there were with changes in
      the proportions with treatment. Regardless of the treatment method, ratios in
      some patients moved toward the divine proportion, while those in others moved
      away from it. A comparison of the two treatment groups both before and after
      treatment showed that the mean group values for some of the proportions differed.
      These differences could largely be explained by differences in growth status and
      treatment method. CONCLUSION: Neither treatment method was more likely to result
      in a greater number of divine proportions, and the achievement of divine
      proportions seemed to have little, if any, influence on overall aesthetic
      outcomes.

PMID- 16429876
TI  - Comparison of three brands of round stainless steel wires used in the Begg and
      tip-edge techniques.
AB  - OBJECTIVE: To compare the properties of three brands of stainless steel
      orthodontic wires: "Bow-Flex Wire", "TP Original Wire Premier Plus" and
      "Australian Wire Special Plus". METHOD: The surface appearance, stiffness,
      elastic modulus and relaxation of coiled and straight round wires in four
      diameters 10.016 inch, 0.018 inch, 0.020 inch and 0.022 inch) were compared.
      RESULTS: "Australian Wire Special Plus" wire had a rougher surface than "Bow
      Flex" and "TP Original Wire Premier Plus" wires. For all diameters "Australian
      Wire Special Plus" coiled wire was stiffer, had a higher elastic modulus, and
      lower relaxation than the corresponding "Bow-Flex" and "TP Original Wire Premier
      Plus" wires. All coiled samples were stiffer and had a higher elastic modulus
      than corresponding straight wires from the same manufacturer. CONCLUSION:
      "Australian Wire Special Plus" 0.016 inch coiled wire is recommended for the
      initial treatment phase in the Begg and the Tip-Edge techniques. Either coiled or
      straight 0.018 inch, 0.020 inch or 0.022 inch wires from both manufacturers are
      suitable for phases II and III in both techniques.

PMID- 16429877
TI  - Lip curve changes in males with premolar extraction or nonextraction treatment.
AB  - AIM: This retrospective study was designed to compare the responses of the upper
      and lower lip curves in young growing males, to orthodontic treatment involving
      either four premolar extractions or the holding of the E-spaces without premolar
      extractions. METHOD: Pre- and post-treatment lateral cephalograms of 67 premolar
      extraction and 30 nonextraction patients were assessed. The results were
      subjected to analysis of variance to search for statistically significant
      differences amongst the pretreatment variables and changes in depths of lip
      curves. Pearson's correlation coefficients were also calculated and stepwise
      regression analysis undertaken. RESULTS: A wide range of lip curve behaviour was
      seen in individual patients within all groups. No significant differences were
      found in the change in depth of lip curve amongst the various extraction and
      nonextraction groups. The inherent morphology of the soft tissues appeared to be
      the greatest determinant of lip curve behaviour with treatment. CONCLUSIONS: It
      would appear that neither premolar extraction nor nonextraction treatment, if
      based on appropriate diagnostic criteria and followed with competent clinical
      management, will necessarily lead to direct effects on lip curvature.

PMID- 16429878
TI  - Prediction and causes of open gingival embrasure spaces between the mandibular
      central incisors following orthodontic treatment.
AB  - BACKGROUND: An open gingival embrasure space (OGES) between the mandibular
      incisors, also known as a "black triangle" (BT), can be an undesirable outcome of
      adult orthodontic treatment. OBJECTIVES: The purpose of this study was to
      determine the parameters that contributed most to the occurrence of an OGES
      between the mandibular central incisors, the area with the highest incidence of
      BT in the lower arch following orthodontic treatment. METHODS: A stepwise
      regression model was used to identify the variables (age, crowding, treatment
      duration, alveolar bone height, and six variables describing crown morphology)
      related independently to OGES score. Intra-oral photographs taken before and
      after orthodontic treatment, study models and intra-oral radiographs of 60
      patients were used. Embrasures between the mandibular central incisors were
      measured and classified into three types: papilla filling, pinpoint, and BT.
      RESULTS: Age at the first consultation, length of active treatment and maximum
      crown width were larger in the BT group than in the normal group. In contrast,
      incisal edge - centre of the contact point, upper contact point - lower contact
      point, mesial CEJ - distal CEJ, and mesial CEJ - distal CEJ / maximum crown width
      were smaller in the BT group than in the normal group. Variation in OGES score
      was explained by the independent contributions of age at the first consultation,
      duration of active treatment, maximum crown width, and mesial CEJ - distal CEJ
      width. The multiple regression coefficient was 0.98, and the regression
      coefficient square was 96 per cent. CONCLUSION: We conclude that age at the first
      consultation, duration of active treatment, and crown morphology are involved in
      OGES manifestation. We suggest also that BT occurrence may be predictable prior
      to treatment.

PMID- 16429879
TI  - Effects of adenoidectomy and changed mode of breathing on incisor and molar
      dentoalveolar heights and anterior face heights.
AB  - BACKGROUND: Mouth breathing may affect facial form and the positions of the
      teeth. OBJECTIVES: To determine whether the increased dentoalveolar and facial
      heights found in mouth breathing children with enlarged adenoids are maintained
      following adenoidectomy and changed mode of breathing from mouth to nose.
      METHODS: The subjects were Swedish children, either mouth breathers with nasal
      obstruction caused by large adenoids, or nose breathers. The children in the
      mouth breathing group were adenoidectomized at seven years of age and changed
      from mouth breathing to nose breathing. The unoperated subjects were age and sex
      matched to the operated subjects, and both groups were followed up again at 12
      years of age. The incisor and molar dentoalveolar heights and anterior face
      heights, measured on lateral cephalometric radiographs, were compared prior to
      adenoidectomy and at 12 years of age. RESULTS: Significant intra-group increases
      were found for all dentoalveolar heights and 5 out of 6 facial heights. Only the
      ratio of upper anterior to lower anterior face height in the controls was not
      different statistically. Upper posterior dentoalveolar height was significantly
      larger (p < 0.05) in the adenoidectomized group compared with the controls at
      follow up, but not before adenoidectomy. Lower face height was significantly
      longer (p < 0.001) in the adenoidectomized group compared with the control group
      initially, and at follow up (p < 0.01). Initially, the ratio of upper face height
      to lower face height was significantly larger (p < 0.001) in the control group
      than the adenoidectomized group, but the groups were similar at follow up. Small,
      but statistically significant, correlations were found between the changes in
      upper molar dental height and the mode of breathing (p < 0.05) in the
      adenoidectomized group, and between the change in the ratio of upper to lower
      face heights and the mode of breathing (p < 0.01). CONCLUSION: The changes in the
      dentoalveolar heights of the maxillary molars, and the ratio of the upper and
      lower anterior face heights seem to be associated with the change in mode of
      breathing from mouth to nose breathing after adenoidectomy.

PMID- 16429880
TI  - A comprehensive survey of retention procedures in Australia and New Zealand.
AB  - OBJECTIVES: This survey aimed to identify consistencies in retention procedures.
      METHODS: Three hundred Australian orthodontists and 70 New Zealand orthodontists
      were randomly selected for the study. A questionnaire gathered their views
      regarding the most commonly used retainers, wire types and sizes of bonded
      retainers, factors influencing the design of retainers, duration of regular
      retention, definition of permanent retention, percentage of cases that needed
      permanent retention, factors influencing the decision to use permanent retention,
      changes in retention protocols over the last five years, and reasons for such
      changes. RESULTS: Upper invisible and lower canine-to-canine bonded retainers
      were the most commonly used retainers. Pretreatment tooth position was the major
      factor influencing the design of retainers, and most respondents preferred bonded
      retainers. The majority preferred multistrand stainless steel wire for bonded
      retainers. The most common wire size was 0.0175 inch. Orthodontists more commonly
      recommended a regular retention period of more than two years, and defined
      permanent retention as "lifetime". Orthodontists applied permanent retention to
      either a very high or very low percentage of their cases. A high percentage of
      respondents made changes to their retention protocols over the past five years.
      There was no relationship between factors influencing the design of retainers and
      the preferred type of retainer. There was no consensus on the major factor
      influencing the decision to use permanent retention. CONCLUSIONS: Retention
      procedures are variable and dependent largely on personal preferences. There does
      not seem to be any consistent pattern in the application of retention
      methodologies.

PMID- 16429882
TI  - Tooth and lip responses to three commonly prescribed premolar extraction
      sequences: a review of recent research findings.
AB  - AIM: To review and discuss the dental and lateral profile soft tissue effects of
      orthodontic treatment involving three different premolar extraction patterns
      (4/4, 4/5, 5/5). METHOD: The results of three previously reported studies were
      compared and discussed. RESULTS: Wide ranges of individual variation were found
      for the amounts of forward molar movement and incisor retraction, and for changes
      in the depths of upper and lower lip curves within all three premolar extraction
      pattern groups. The amount of pretreatment crowding and the residual space
      following initial alignment were the two factors most likely to influence changes
      in tooth positions during treatment. Treatment changes in the curvature of the
      lips were influenced by the pretreatment thickness of the lips at the vermilion
      level. CONCLUSION: Factors other than simply the choice of premolar extraction
      pattern influence positional changes in the molars, incisors and lips during
      orthodontic treatment.

PMID- 16429881
TI  - Moment to force ratio characteristics of three Japanese NiTi and TMA dosing
      loops.
AB  - OBJECTIVES: This in vitro study investigated the loads ("forces"), moments and
      moment:force ratios (M:F) generated during activation and deactivation of three
      closing loop designs constructed from two different orthodontic wire alloys.
      METHOD: The forces and moments of non-preactivated vertical U-Loops, symmetrical
      T-Loops, and asymmetrical T-Loops (X-Loops) made from titanium molybdenum alloy
      (TMA) and Japanese nickel titanium alloy (NiTi) were measured at 35.6 degrees C
      +/- 0.5 degrees C. The M:F ratios generated during activation and deactivation
      were calculated for each loop. Analysis of covariance was used to identify
      statistical differences between loop material and design. RESULTS: The forces,
      moments and M:F ratios produced by the NiTi closing loops were significantly less
      than those from the TMA loops. NiTi T-Loops produced a relatively constant force
      during activation compared to the same design in TMA. The TMA X-loop produced a
      maximum M:F ratio of 9.4:1. No closing loop produced the optimum M:F ratio
      required for translational en masse tooth movement. CONCLUSIONS: Optimum M:F
      ratios for translation are not possible with non-preactivated vertical U-Loops,
      symmetrical T-Loops, and asymmetrical T-Loops (X-Loops) made of NiTi and TMA
      alloys.

PMID- 16429883
TI  - An academic question.

PMID- 16429884
TI  - Variation, treatment, and redefining orthodontics.

PMID- 16429885
TI  - Orthodontics in the age of enhancement.

PMID- 16429886
TI  - Common perioperative problems for the cardiac anesthesiologist.

PMID- 16429887
TI  - Multimodal detection of perioperative myocardial ischemia.
AB  - Cardiac anesthesiologists have the responsibility to detect myocardial ischemia
      in a timely manner, which can be a challenging task in the perioperative
      environment. Transesophageal echocardiography pulmonary artery catheterization,
      and electrocardiography are the 3 major methods available for monitoring
      perioperative ischemia. Echocardiography, the newest and most sophisticated
      method, has been shown to be highly sensitive for detecting ischemia associated
      with systolic dysfunction. Echocardiography can detect wall-motion abnormalities
      before electrocardiographic changes develop in patients who are likely to
      experience supply-mediated ischemia. Perioperative ischemia that occurs after
      bypass and is detected using transesophageal echocardiography has been found to
      be related to an adverse outcome. However, the use of echocardiography has some
      limitations, including the detection of abnormalities not induced by ischemia and
      the presence of ischemia in areas not visible in the view selected. Pulmonary
      artery catheterization can provide information about systolic dysfunction,
      diastolic dysfunction, and mitral regurgitation, but the sensitivity and safety
      of catheterization have been questioned. Electrocardiography can be a superb
      monitoring device as long as clinicians pay adequate attention to lead selection
      and placement, filter selection, and gain adjustment. The optimal monitoring
      approach should integrate all 3 available monitoring systems in order to increase
      the likelihood of detecting both supply- and demand-mediated ischemia.

PMID- 16429888
TI  - Management of systemic and pulmonary hypertension.
AB  - The major therapeutic approach to systemic and pulmonary hypertension and
      vasospasm in cardiac surgery patients involves the use of parenteral agents that
      reverse systemic vasoconstriction and produce vasodilation. Potential
      pharmacologic approaches include 1) alpha1-adrenergic receptor blockers,
      ganglionic blockers, and calcium channel blockers; 2) central alpha2-adrenergic
      receptor agonists, dopamine1-adrenergic receptor agonists, potassium channel
      modulators, and vascular cyclic nucleotide stimulators; 3) phosphodiesterase
      enzyme inhibitors, and 4) angiotensin-converting enzyme inhibitors. Of the
      currently available intravenous vasoactive therapies, the mainstay agents are the
      nitrovasodilators and the dihydropyridine-type calcium channel blockers. The
      nitrovasodilators, a diverse group of drugs that achieve vascular relaxation by
      stimulating cyclic nucleotides and thereby releasing nitric oxide, include
      nitroglycerin and sodium nitroprusside. Although these drugs are useful, rapid
      development of tolerance is a drawback to nitroglycerin, while nitroprusside can
      cause coronary steal and increase intracranial pressure. Intravenous
      dihydropyridine-type calcium channel blockers inhibit mechanical responses of
      cardiac muscle and vascular smooth muscle by blocking inward calcium currents.
      Nicardipine is an arterial specific vasodilator. Treatment for vasospasm is
      usually empiric; pharmacologic options include nitroglycerin, but dihydropyridine
      calcium channel blockers and phosphodiesterase inhibitors should also be
      considered.

PMID- 16429889
TI  - Management of temperature during and after cardiac surgery.
AB  - Neurologic injury is a devastating complication of cardiac surgery. Cerebral
      cooling is an important aspect of hypothermic cardiopulmonary bypass in some
      patients, because hypothermia is the only reliable method of neuroprotection
      against injuries related to cerebral ischemia. Hypothermia may afford
      neuroprotection by a variety of mechanisms, including reduction in cerebral
      metabolic rate, decreased excitatory transmitter release, reduced ion influx, and
      reduced vascular permeability. Conversely, hyperthermia, even if mild (2-3
      degrees C), is harmful; it aggravates ischemic neuronal injury and accelerates
      neuronal death. In patients with acute strokes, hyperthermia worsens prognosis
      with respect to stroke severity, infarct size, mortality, and outcome in
      survivors. The degree of temperature discrepancy among standard monitoring sites
      in individual patients is often striking. The differences between jugular bulb
      temperature and rectal or bladder temperature are particularly large. Blood
      temperature in the arterial line leading from the oxygenator may be the most
      consistently accurate indicator of cerebral temperature. When hypothermia is used
      to protect vital organs during cardiopulmonary bypass, the cooling phase should
      be adequate, and the rewarming phase must be carefully managed. Hyperthermia may
      be as hazardous during the postoperative period as during surgery, exacerbating
      the extent of tissue injury if an overt stroke has occurred. Postoperative
      hyperthermia correlates with a greater degree of cognitive dysfunction measured 6
      weeks after cardiac surgery. In conclusion, cardiac anesthesiologists can reduce
      the risk of inadvertent hyperthermia by selecting the best sites for temperature
      monitoring, carefully controlling the rewarming process, and continuing
      temperature monitoring during the postoperative period.

PMID- 16429890
TI  - In search of Vivien Thomas.

PMID- 16429891
TI  - Stem cell treatment of the heart: a review of its current status on the brink of
      clinical experimentation.
AB  - Stem cells are multipotent, undifferentiated cells capable of multiplication and
      differentiation. Preliminary experimental evidence suggests that stem cells
      derived from embryonic or adult tissues (especially bone marrow) may develop into
      myocardial cells. Some experts believe that this phenomenon occurs naturally in
      human beings, specifically during recovery from a myocardial infarction.
      Recently, stem cells have been used with the therapeutic intention of
      regenerating damaged tissues. Cardiac experiments, mainly with adult homologous
      stem cells, have proved that this therapy is safe and may improve myocardial
      vascularization and pump function. We review current fundamental concepts
      regarding the normal development of embryonic stem cells into myocardial tissue
      and the heart as a whole. We describe the multiple conditions that naturally
      enable a stem cell to become a myocardial cell and a group of stem cells to
      become a heart. We also discuss the challenge of translating basic cellular and
      molecular mechanisms into effective, clinically relevant treatment options.

PMID- 16429893
TI  - Mathematical Model analysis of Wallstent and Aneurx: dynamic responses of bare
      metal endoprosthesis compared with those of stent-graft.
AB  - We performed this study in order to analyze the mechanical properties of bare
      metal Wallstent endoprostheses and of AneuRx stent-grafts and to compare their
      responses to hemodynamic forces. Mathematical modeling, numerical simulations,
      and experimental measurements were used to study the 2 structurally different
      types of endoprostheses. Our findings revealed that a single bare-metal Wallstent
      endoprosthesis is 10 times more flexible (elastic) than is the wall of the
      aneurysmal abdominal aorta. Graphs showing the changes in the diameter and length
      of the stent when exposed to a range of internal and external pressures were
      obtained. If the aorta is axially stiff and resists length change, a force as
      large as 1 kg can act in the axial direction on the aortic wall. If the stent is
      not firmly anchored, it will migrate. In contrast, a fabric-covered, fully
      supported, stent-graft such as the AneuRx is significantly less compliant than
      the aorta or the bare-metal stent. During each cardiac cycle, the stent frame
      tends to move due to its higher elasticity, while the fabric resists movement,
      which might break the sutures that join the fabric to the frame. Elevated local
      transmural pressure, detected along the prosthesis graft, can contribute to
      material fatigue.

PMID- 16429894
TI  - Hormone replacement therapy is safe in women undergoing coronary artery bypass
      grafting.
AB  - In postmenopausal women, hormone replacement therapy (HRT) does not substantially
      reduce the incidence of cardiovascular disease and may produce a short-term
      increase in risk. Therefore, we investigated whether HRT increased risk in
      patients with severe coronary artery disease necessitating surgery We
      prospectively studied 4,782 patients undergoing coronary artery bypass grafting
      at 70 centers in 17 countries from November 1996 through June 2000. Patients were
      selected using a systematic sampling technique. Mortality, major morbidity, and
      transfusion requirements were compared among 3 groups: men (n=3,840), women
      receiving HRT (n= 144), and women not receiving HRT (n=798). Women actively
      receiving HRT, compared with women not receiving HRT or with men, were at no
      greater risk of developing the following fatal or non-fatal complications: death
      (2.8% vs 4.4% vs 2.8%, respectively; P=0.05), myocardial infarction (6.3% vs 7.0%
      vs 7.7%; P=0.67), central nervous system complication (2.1% vs 2.8% vs 2.9%;
      P=0.85), or renal dysfunction (0.7% vs 5.3% vs 4.8%; P=0.06). Incidence of
      postoperative congestive heart failure was significantly lower in men (7.7%) than
      in women receiving HRT (12.5%; P=0.04) and in women without HRT (12.8%; P
      <0.0001). Fewer men (61%) needed red blood cell transfusion than did women
      receiving HRT (79%) and women without HRT (88%) (P <0.0001 compared with both
      other groups). However, the need for fresh frozen plasma transfusions was
      significantly less in women receiving HRT (16%) than in women not receiving HRT
      (25%; P=0.01). We conclude that HRT administration before coronary artery bypass
      grafting does not increase women's risk of any adverse outcome.

PMID- 16429895
TI  - Intra-aortic filtration: capturing particulate emboli during aortic cross
      clamping.
AB  - Particulate emboli are an important factor in the development of complications
      after cardiac surgery. The use of an intra-aortic filter during aortic declamping
      has proved safe and effective in reducing the incidence of embolic complications.
      Because aortic cross-clamping is also associated with the risk of embolism, we
      measured the release of particulate emboli at the time of aortic cross-clamping
      and at declamping. We deployed intra-aortic filters (Edwards EMBOL-X Slim
      Protection System) at 2 different times during 15 consecutive cardiac procedures
      with cardiopulmonary bypass. Filter A was inserted before aortic cross-clamping
      and left in place for a mean time of 3 minutes, and Filter B was inserted before
      aortic declamping for a mean of 17 minutes. An independent institution performed
      histopathologic examination. All filters captured particulate emboli, independent
      of the patients' degree of proximal aortic atherosclerotic disease. Macroscopy
      showed that Filter A captured more particles (mean, 70 +/- 2.6) in 7 of 15
      patients (46.7%), Filter B captured more particles (mean, 6.7 +/- 2.6) in 5 of 15
      patients (33.3%), and the filters captured the same number in 3 of 15 patients
      (20%). Microscopy showed that both filters captured fibrous atheroma or fibrous
      cap in 10 of 15 patients. We observed no complications related to the use of the
      filters. Aortic cross-clamping is associated with a high risk of embolism. We
      suggest that optimal protection against embolism during cardiac surgery can be
      achieved by applying intra-aortic filtration not only before aortic declamping
      but also before aortic cross-clamping.

PMID- 16429892
TI  - Pump or no pump for coronary artery bypass: current best available evidence.
AB  - Coronary artery bypass grafting has been performed predominantly with the use of
      cardiopulmonary bypass and cardioplegic arrest, which allows optimization of the
      surgical field and consistent placement of grafts. However, the use of
      cardiopulmonary bypass is also associated with numerous complications. A surgical
      technique avoiding cardiopulmonary bypass should, in theory, reduce the incidence
      of such complications and lead to improved patient outcomes. This assumption has
      rekindled interest in performing off-pump coronary artery bypass surgery, which
      is currently the focus of scientific scrutiny. The existing world medical
      literature contains a staggering amount of research related to this technique.
      Although the available evidence from a large number of randomized clinical
      trials, nonrandomized clinical trials, propensity-matched analyses, and
      experimental data suggests that outcomes are better after off-pump than after on
      pump coronary artery bypass surgery, skepticism still exists about the safety and
      efficacy of the off-pump technique. In the present era of evidence-based
      medicine, results from randomized clinical trials are given the highest
      recognition. This review attempts to evaluate the best currently available
      evidence from clinical trials about the safety and efficacy of off-pump coronary
      artery bypass surgery.

PMID- 16429896
TI  - Surgical treatment of aortobronchial and aortoesophageal fistulae due to thoracic
      aortic aneurysm.
AB  - We present a review of our single-institution experience, over 19 years, with
      aortobronchial and aortoesophageal fistulae due to descending thoracic aortic
      aneurysm. We conducted a retrospective chart review of 10 cases involving surgery
      for aortobronchial and aortoesophageal fistulae in our clinic from February 1985
      through October 2004. Pathologic or predisposing conditions associated with
      aortobronchial fistula were descending thoracic aortic aneurysm (n=8), previous
      aortic surgery (n=1), and concomitant aortoesophageal fistula (n=1). Three
      patients presented emergently with aortobronchial fistula (n=2) and
      aortoesophageal fistula (n=1). Ages of the 10 patients ranged from 42 to 74 years
      (median, 63 years). The median cross-clamp time was 34 minutes (range, 27-41
      min). Repairs, in 9 patients, involved an inlay of prosthetic tube graft using
      the clamp-and-sew technique, and in 1 patient repair involved patch aortoplasty.
      The operative mortality rate was 20%:1 patient had acute concomitant
      aortoesophageal and aortobronchial fistulae, and another had chronic
      aortobronchial fistula. There was no embolic stroke or paraplegia. During follow
      up (median, 2.5 years), there were no deaths or postoperative morbidity We
      conclude that repair of aortobronchial and aortoesophageal fistulae using the
      clamp-and-sew technique can be performed with acceptable operative mortality and
      long-term results. However, the mortality rate continues to be highly significant
      in patients with acute bleeding aortobronchial fistula or with aortoesophageal
      fistula, despite rapid surgical intervention.

PMID- 16429897
TI  - Management of vascular infection in the groin.
AB  - We performed this retrospective study in order to evaluate the effectiveness of
      different surgical methods in the treatment of inguinal vascular infections.
      Fourteen consecutive patients underwent surgical treatment of such infections
      from 1996 through 2004 in our clinic. The mean age was 52 +/- 16 years. Seven of
      the 14 patients underwent emergency operation due to bleeding or acute ischemia.
      The events that caused inguinal infection were synthetic graft implantation in 8
      patients, gunshot injury in 1, arterial catheterization in 2, femoropopliteal
      saphenous vein bypass operation in 1, and motor vehicle accident with abdominal
      wall laceration in 2. The most common infecting pathogen was Staphylococcus
      aureus (7 patients). Sixteen operations were performed in 14 patients. These
      operations included lateral femoral bypass (5), obturator bypass (5),
      revascularization with homograft (5), and femorofemoral bypass (1). All inguinal
      infections were completely cured after surgery. Early complications included poor
      wound healing (4 patients), minor amputation (1 patient), and extension of
      infection to the distal anastomosis of the obturator bypass and false aneurysm
      formation (1 patient). Late complications were acute homograft occlusion of a
      femorofemoral bypass and thrombosis of a below-knee lateral femoral bypass. There
      was no operative or late mortality. All patients were followed up for a mean of
      48.1 +/- 21.9 months. We did not encounter any aneurysmal degeneration, rupture,
      or reinfection in homograft patients during follow-up. We conclude that vascular
      infections of the groin can be cured by proper selection and application of one
      of the above techniques.

PMID- 16429898
TI  - Novel left ventricular assist systems I and II for cardiac recovery: the driver.
AB  - We have recently described the Novel Left Ventricular Assist Systems (Novel LVAS)
      I and II, which avoid cannulation of cardiac chambers and synchronize pumping
      with the patient's electrocardiogram. We now describe the drive system in more
      detail. The drive unit is an air-driven pulsatile system. The driver's parameters
      can be programmed. This electro-pneumatic unit contains 3 modules. A remarkable
      feature of the driver system is that it contains 2 pneumatic units that alternate
      in their function every 15 minutes. This prevents overheating and component
      fatigue or failure, and it enables the use of smaller units. If one of the units
      fails, an alarm will warn of the problem, and the other will continue
      indefinitely. This LVAS is synchronized with the patient's ECG, which enables it
      to eject the stroke volume during diastole and in this way to act as a chronic
      counterpulsator. We have designed the Novel LVAS to operate at a low-frequency
      rate. This fact, together with the electrocardiographic synchronization, offers
      the best prospect for myocardial recovery in patients who are also receiving beta
      adrenergic blocking agents. This dual therapy will help adjust heart rate to pump
      frequency.

PMID- 16429899
TI  - Orthotopic heart transplantation in a patient with D-transposition of the great
      arteries: after a Mustard procedure.
AB  - During heart transplantation, the atrial septum is most often used to reconstruct
      the right atrial reservoir. We report the case of a patient with corrected D
      transposition of the great arteries who underwent successful cardiac
      transplantation despite the lack of an atrial septum. We then used the donor
      heart's atrial septum for the roof of the left atrium and used the recipient's
      left atrium for the back wall of the left atrium. The outcome was a more
      anatomically positioned transplanted heart, which avoided the duplication of the
      right and left atria that occurs in conventional orthotopic transplantation and
      that often leads to left-lower-lobe atelectasis and tricuspid regurgitation. This
      method of orthotopic transplantation should be considered for, but not limited
      to, the growing number of adults with congenital heart disease who require heart
      transplantation.

PMID- 16429900
TI  - Do absorbable sutures exacerbate presternal scarring?
AB  - We investigated cosmetic outcomes of the midline sternotomy incision. A
      randomized clinical trial was conducted in 60 patients who underwent surgery
      through a midline sternotomy incision. Patients were divided into groups A (n=30)
      and B (n=30). In addition, the incision line was also divided into 2 regions
      (upper and lower halves) in each group. In group A, the upper half of the skin
      was closed with absorbable 4-0 braided polyglycolic acid sutures (Sentesorb, Boz;
      Ankara, Turkey), and the lower half was closed with 4-0 nonabsorbable
      monofilamentous polypropylene suture (Monoplene, Boz), and vice versa in group B.
      Scar width and height were measured and photographed at the 6th postoperative
      month. In both groups, the lower part of the incision showed inferior cosmetic
      results, regardless of the suture material (P <0. 05). On the other hand, the
      upper part of the incision in group A (the area of absorbable polyglycolic acid
      sutures) was significantly more hypertrophic. We conclude that monofilament nylon
      sutures diminish the risk of hypertrophic scarring, in comparison with absorbable
      sutures. In the lower half of the sternotomy scar, increased tension and relative
      mobility of the skin over the xiphoid process lead to inferior cosmetic results,
      regardless of the suture material used.

PMID- 16429901
TI  - A simplified technique of performing splenorenal shunt (Omar's technique).
AB  - The splenorenal shunt procedure introduced by Robert Linton in 1947 is still used
      today in those regions of the world where portal hypertension is a common
      problem. However, because most surgeons find Linton's shunt procedure technically
      difficult, we felt that a simpler technique was needed. We present the surgical
      details and results of 20 splenorenal anastomosis procedures performed within a
      period of 30 months. Half of the patients (Group I) underwent Linton's
      conventional technique of splenorenal shunt; the other half (Group II) underwent
      a newly devised, simplified shunt technique. This new technique involves
      dissection of the fusion fascia of Toldt. The outcome of the 2 techniques was
      identical with respect to the reduction of preshunt portal pressure. However, our
      simplified technique was advantageous in that it significantly reduced the
      duration of surgery (P <0.001) and the amount of intraoperative blood loss (P
      <0.003). No patient died after either operation. Although Linton's splenorenal
      shunt is difficult and technically demanding, it is still routinely performed.
      The new technique described here, in addition to being simpler, helps achieve
      good vascular control, permits easier dissection of the splenic vein, enables an
      ideal anastomosis, decreases intraoperative blood loss, and reduces the duration
      of surgery. Therefore, we recommend the routine use of this simplified technique
      (Omar's technique) for the surgical treatment of portal hypertension.

PMID- 16429902
TI  - Ruptured aneurysm of the right sinus of valsalva associated with a ventricular
      septal defect and an anomalous coronary artery.
AB  - Aneurysms of the sinus of Valsalva are extremely rare. Ruptured aneurysms of the
      sinus of Valsalva are frequently associated with other congenital defects,
      particularly with ventricular septal defect, aortic valve regurgitation, and
      bicuspid aortic valve. We describe the case of a 26-year-old man who had a
      ruptured aneurysm of the right coronary sinus, a ventricular septal defect, and
      an anomalous origin of the right coronary artery. Successful surgical correction
      of the aneurysm and ventricular septal defect was performed with patch repair and
      aortic valve replacement. A review of the English-language medical literature
      revealed only 1 other case of a sinus of Valsalva aneurysm associated with a
      ventricular septal defect and an anomalous coronary artery. Previously published
      reports of the coexistence of a single coronary artery with a sinus of Valsalva
      aneurysm or with a ventricular septal defect, and their management, are discussed
      herein.

PMID- 16429903
TI  - Aortic sinus aneurysm and associated defects: can we extrapolate a morphogenetic
      theory from pathologic findings?

PMID- 16429904
TI  - Pharmacologic resolution of functional outflow tract obstruction after mitral
      valve repair.
AB  - A 74-year-old woman with mitral regurgitation secondary to ruptured chordae
      tendineae, complicated by a cleft in the posterior mitral leaflet and a severely
      calcified mitral annulus, underwent mitral valve repair by implantation of
      polytetrafluoroethylene chords and closure of the cleft, without the use of an
      annuloplasty ring. Immediately after the repair severe left ventricular outflow
      tract obstruction developed secondary to the systolic anterior motion of the
      mitral valve. Echocardiography identified the cause as functional, in the
      presence of a hypertrophic left ventricle with no significant preoperative
      intraventricular dynamic gradient. The obstruction was severe enough to render
      impossible the weaning of the patient from cardiopulmonary bypass. This problem
      was reversed by the infusion of beta-blocking agents into the extracorporeal
      circuit.

PMID- 16429906
TI  - Pericardial hydatid cyst mimicking acute coronary syndrome.
AB  - Cardiac hydatid cysts are found mostly within myocardium. Only a few cases of
      pericardial location have been reported. Patients with hydatid cysts are usually
      asymptomatic. A 46-year-old man with clinical and electrocardiographic features
      mimicking acute myocardial ischemia was hospitalized for further evaluation.
      Detailed imaging and laboratory investigation revealed a pericardial hydatid
      cyst. The patient underwent operation for curative excision. After surgery, the
      patient's symptoms resolved and his clinical status improved. We think that
      pericardial hydatid cyst should be considered in the differential diagnosis of
      patients with angina-like pain-especially in geographic areas where hydatid cysts
      are endemic.

PMID- 16429905
TI  - Left ventricular assist device implantation in a patient with congenitally
      corrected transposition of the great arteries.
AB  - Congenitally corrected transposition of the great arteries (ccTGA) is a rare
      anomaly characterized by atrioventricular and ventriculo-arterial discordance and
      several other malformations that eventually lead to heart failure. We describe
      the case of a 53-year-old woman with ccTGA and aortic insufficiency who was a
      candidate for heart transplantation due to end-stage congestive heart failure.
      Her condition deteriorated before a suitable donor heart could be found;
      therefore, we placed a left ventricular assist device in the right (systemic)
      ventricle. Concomitantly, we removed the aortic (systemic) valve, closed the
      aortic annulus with a bovine pericardial patch, and repaired the mitral valve.
      The patient recovered uneventfully and was discharged from the hospital 2 months
      postoperatively. She underwent cardiac transplantation approximately 6 months
      later and continued to do well after 18 months.

PMID- 16429907
TI  - Aortic root replacement for reoperation of dissecting aneurysm of the
      interventricular septum.
AB  - Dissection of the interventricular septum due to an aneurysm of the left sinus of
      Valsalva is a very rare cardiac condition. We report a case in which we used a
      modified Bentall procedure for aortic root replacement in reoperating on a sinus
      of Valsalva aneurysm that had dissected into the interventricular septum.

PMID- 16429908
TI  - Arterial conduits should be evaluated preoperatively in coronary artery bypass
      patients with pseudoxanthoma elasticum.
AB  - A 74-year-old man who had pseudoxanthoma elasticum presented with unstable angina
      and underwent urgent coronary artery bypass grafting. Preoperative angiography
      did not include the internal mammary arteries. Intraoperatively, the left
      internal mammary artery was found to be diseased and could not be used. This case
      lends support to the need for thorough preoperative evaluation, including
      angiography, of potential arterial conduits in patients with pseudoxanthoma
      elasticum.

PMID- 16429910
TI  - 19-year patency of a coronary-coronary venous bypass graft.
AB  - No data are available on the long-term outcome of coronary-coronary venous bypass
      grafting. We describe a case in which we successfully stented a discrete,
      critical stenosis of a coronary-coronary venous graft that had been placed 19
      years earlier to minimize manipulation of a severely calcified ascending aorta.
      Coronary-coronary bypass grafting should be considered in cases involving severe
      aortic calcification, in situ grafts of inadequate length, and stenosed or
      occluded subclavian arteries. Such a bypass can be performed with either
      saphenous vein or arterial conduits, and it provides a flow rate similar to that
      of aortocoronary bypass. This option could be borne in mind as a 2nd-choice
      technique for the durable restoration of coronary blood flow in selected cases.

PMID- 16429909
TI  - Ovarian vein and caval thrombosis.
AB  - We present an illustrative case of postpartum ovarian vein thrombosis and
      describe its clinical presentation, differential diagnosis, and management. This
      pathologic process may produce clinical complications or a catastrophic outcome.
      These adverse events may be avoided if an expeditious diagnosis is made and
      appropriate treatment is instituted. This mandates a high index of suspicion, the
      ability to rule out the presence of other processes that may produce similar
      symptoms in the postpartum patient, and the appropriate triage of specific
      patients to either medical or surgical management.

PMID- 16429911
TI  - Ruptured aneurysm of the noncoronary sinus of valsalva.
AB  - Sinus of Valsalva aneurysm is a rare disorder. It is usually congenital, but
      other origins have been described. It may be asymptomatic, or it may present as
      angina or with symptoms of valvular insufficiency or outflow obstruction. Once
      ruptured, it often produces hemodynamic instability. Diagnosis should be pursued
      with transesophageal echocardiography or catheterization. A 50-year-old man was
      admitted with symptoms of congestive heart failure. His functional capacity had
      declined over 3 years, worsening over the last 3 weeks. His medical history was
      significant only for gunshot to the right hemithorax, at age 25. He was found to
      be in distress, with signs of heart failure, S3 and S4 gallop, and systolic and
      diastolic murmur at the right sternal border. Two-dimensional echocardiography
      revealed an ejection fraction of 0.25, dilated left and right atria, and a sinus
      of Valsalva aneurysm with an aortic-right atrial shunt. Left and right heart
      catheterization revealed metallic fragments in the anterior chest wall, normal
      coronary arteries, and a step-up in the oxygen saturation from the inferior vena
      cava to the pulmonary artery. Aortography revealed that the aneurysm had ruptured
      into the right atrium. Surgical repair was performed. Ruptured sinus of Valsalva
      aneurysm demands prompt diagnosis and treatment. Patients are often men, in the
      3rd or 4th decade of life when rupture occurs. In our patient, the position of
      the bullet and its fragments, leaflet perforation, and lack of a predisposing
      infection suggest a causal association between the gunshot wound and the
      aneurysm.

PMID- 16429913
TI  - Starfish-assisted off-pump obliteration of massive coronary arteriovenous
      fistulae.
AB  - Coronary arteriovenous fistula is a rare congenital heart disease. A 71-year-old
      woman suffered from heart failure due to massive coronary arteriovenous fistulae
      from the right coronary artery and left circumflex artery to the coronary sinus.
      Using the off-pump technique, we successfully performed Starfish-assisted
      obliteration of the fistulae. Intraoperative transesophageal echocardiography was
      used to confirm the complete elimination of the abnormal shunt flow.

PMID- 16429912
TI  - Giant, dissecting, high-pressure pulmonary artery aneurysm: case report of a 1
      year natural course.
AB  - We report the rare subchronic clinical course of a giant, dissecting pulmonary
      artery aneurysm in an oligosymptomatic middle-aged woman who had idiopathic
      pulmonary hypertension. Diagnosis was simple with the use of echocardiography and
      multislice computed tomography. Conversely, deciding on the treatment was
      difficult, because prominent surgeons declined to perform surgical repair of the
      aneurysm and recommended heart-lung transplantation. Therefore, we were forced to
      treat our patient medically. She survived for 1 year, including 8 months of
      treatment with sildenafil, and then died suddenly while awaiting transplantation.
      Our patient, who had a dissecting, high-pressure pulmonary artery aneurysm, had
      an unexpectedly stable and uneventful clinical course for 1 year, which, under
      more favorable circumstances, might have provided enough time for heart-lung
      transplantation to be performed.

PMID- 16429914
TI  - Myoangiogenesis after cell patch cardiomyoplasty and omentopexy in a patient with
      ischemic cardiomyopathy.
AB  - We describe a procedure to promote angiogenesis and impregnation of skeletal
      myoblast into infarcted myocardium. At the completion of coronary artery bypass
      surgery, the midline sternotomy incision was extended to open the abdomen, and
      the greater omentum was tailored to reach the myocardium. Four pieces of
      autologous rectus muscle were applied to the infarcted left ventricle. This
      implantation was reinforced by the greater omentum. Incisions were closed in the
      usual manner. Postoperatively, the patient showed significant improvements in
      left ventricular ejection fraction (from 0.15 to 0.40) and in exercise tolerance
      (from 3 METs to 6 METs, or 100%). Computed tomographic angiography and positron
      emission tomography demonstrated improved myocardial viability and vascularity in
      the ischemic segments of the left ventricle. Omentopexy and cell patch
      cardiomyoplasty in conjunction with coronary artery bypass surgery may stimulate
      myogenesis and angiogenesis in avascular, dyskinetic scar tissue of left
      ventricle; in this preliminary study, this procedure appeared to improve the
      functional capacity of the left ventricle.

PMID- 16429915
TI  - Deglutition-induced atrial fibrillation.
AB  - We present the case of 38-year-old woman who experienced palpitations on
      swallowing, which were later found to be atrial fibrillation. Her symptoms
      improved on treatment with disopyramide and verapamil. Within 9 months, she was
      weaned from both medications without recurrence of symptoms.

PMID- 16429916
TI  - Superior vena caval bypass using the superficial femoral vein for treatment of
      superior vena cava syndrome.
AB  - We present the case of a 71-year-old woman who had benign, symptomatic, superior
      vena cava syndrome that was treated with open surgical bypass using the
      superficial femoral vein. The patient had an uneventful hospital course and
      experienced relief of her symptoms. We conclude that the superficial femoral vein
      is an acceptable bypass conduit for open surgical management of superior vena
      cava syndrome.

PMID- 16429917
TI  - Cardiovascular Magnetic resonance imaging of sarcoma invading the left atrium and
      pericardium.

PMID- 16429918
TI  - Harmonic contrast transesophageal echocardiography of a soft-parts sarcoma
      metastatic to the heart.

PMID- 16429919
TI  - Huge atrial thrombus causing massive pulmonary and paradoxical embolism via
      patent foramen ovale.

PMID- 16429920
TI  - Left ventricular aneurysm in a 4-year-old boy.

PMID- 16429921
TI  - Use of a ventricular assist device in a single-ventricle patient.

PMID- 16429922
TI  - Histopathology of internal thoracic artery lymph nodes for early diagnosis of
      lymphoma.

PMID- 16429923
TI  - Carotid artery stenting.

PMID- 16429924
TI  - Organized thrombus of tricuspid valve.

PMID- 16429925
TI  - Hyposkillia: deficiency of clinical skills.

PMID- 16429926
TI  - Hyposkillia: deficiency of clinical skills.

PMID- 16429927
TI  - Ruptured acute, infrarenal dissection superimposed on a chronic abdominal aortic
      aneurysm.

PMID- 16429929
TI  - Quantum leaps in orthopedics?

PMID- 16429928
TI  - The case: Your diagnosis? Diagnosis: Elastofibroma dorsi.

PMID- 16429930
TI  - Composite graft replacement of digital tips in adults.

PMID- 16429931
TI  - Treatment of intra-articular comminuted os calcis fractures.

PMID- 16429932
TI  - Staying in rhythm: management of patients at risk for torsade de pointes.

PMID- 16429933
TI  - Diagnosis of peripheral vascular injury in extremity trauma.

PMID- 16429934
TI  - Distal radioulnar joint problems and treatment options.

PMID- 16429935
TI  - Femoral lengthening after transfemoral amputation.
AB  - This retrospective study included four patients with transfemoral amputations who
      had undergone six lengthenings of their residual femurs. Initial femoral bone
      lengths averaged 15.5 cm with a mean final length of 21 cm. The average gain of
      limb length (ischium to end of soft tissue), however, was 2 cm (15%). Second
      lengthenings resulted in only 17% additional bone length, compared to 50% for
      first lengthenings. Treatment time was protracted and complications resulted from
      infection, bone healing, and pin migration. However, all patients reported
      substantial improvement in walking function and prosthetic use.

PMID- 16429936
TI  - Improvement in bone homeostasis following autologous chondrocyte implantation of
      the knee.
AB  - This retrospective review and clinical follow-up demonstrates the effectiveness
      of autologous chondrocyte implantation of the knee. From September 1995 to June
      2001, 24 patients with average follow-up of 26.5 months were evaluated. The mean
      Lysholm score improved from 43.58 before surgery to 71.42 at most recent follow
      up, the modified Cincinnati knee score for overall clinician evaluation improved
      from 2.96 to 6.92, and the mean modified Cincinnati knee score for overall
      patient evaluation improved from 3.21 to 6.13 at P <.05. Seventy-nine percent of
      patients responded that they would have the same knee surgery again and 83% rated
      the results of their knee surgery as good to excellent. Limited radionuclide bone
      scans with single photon emission computed tomography were completed in 11 of the
      patients to assess the physiology and homeostasis of subchondral bone adjacent to
      treated articular cartilage defects. A trend was identified suggesting
      improvement in subchondral bone scores at a mean of 29.6-months follow-up
      compared to preoperative bone scan assessment. There also was a trend towards
      greatest improvement correlating with the patients with the best clinical scores.
      The results of this study suggest that autologous chondrocyte implantation of the
      knee can be successful in improving pain and function in patients with articular
      cartilage defects.

PMID- 16429937
TI  - Ilizarov bone transport for massive tibial bone defects.
AB  - This article reports the treatment of massive tibial bone defects by bone
      transport using the Ilizarov external fixator. Fifteen patients were treated
      using this technique (3 females and 12 males). The defect size ranged between 7
      and 22 cm (average: 10.6 cm). Etiology was infected nonunion in 9 patients,
      nonunion in 5 patients, and recurrent giant-cell tumor in 1 patient. The affected
      site was the tibial diaphysis in 10 patients, the lower tibial metaphysis in 4,
      and the upper tibial epiphysis in 1 patient. The external fixation time ranged
      from 9 months to 17 months (average: 12.27 months). External fixation index
      ranged from 21.8 to 42.5 day/cm (average: 35.7 day/cm). There was no recurrence
      of infection, no recurrence of the tumor, nor fractures after frame removal. We
      had to graft the docking site in 2 patients for delayed union and 2 patients
      developed equinus deformity and had tenoplasty for the Achilles tendon at the
      time of frame removal. Four patients had pin tract infection at > or =1 of the
      wires and this was successfully treated by antibiotic injection at the wire site.
      This study suggests that Ilizarov bone transport is a reliable method to fill
      massive bone defects.

PMID- 16429938
TI  - Does aprotinin reduce blood loss in total hip arthroplasty?
AB  - This prospective randomized study examined the effects of aprotinin during total
      hip arthroplasty (THA). Fifty patients who were enrolled in the study received
      aprotinin or normal saline. Mean intraoperative blood loss was reduced from 1496
      mL in the control group to 1073 mL in the aprotinin group. The mean transfusion
      unit was 1.56 in the aprotinin group and 3.8 in the control group.

PMID- 16429939
TI  - Duplication of the clavicle.

PMID- 16429940
TI  - An unusual presentation of a locked knee.

PMID- 16429941
TI  - Leg-length discrepancy from posterior tibial tendon insufficiency one year after
      total hip arthroplasty.

PMID- 16429942
TI  - Cementless stem fixation and primary stability under physiological-like loads in
      vitro.
AB  - Primary stability and in consequence osteointegration are commonly related to the
      stem anchorage but also to the complex musculoskeletal loading of the hip region.
      This study investigated the influence of metaphyseal and meta-diaphyseal
      anchorage on the primary stability of cementless stems under physiological-like
      loading in vitro. Metaphyseal and meta-diaphyseal anchoring stems (n=6 each) were
      implanted into composite femora. Musculoskeletal loads, validated by in vivo data
      (peak joint force 2348 N), were applied using a mechanical set-up. Interface
      movements were recorded by seven displacement transducers and primary stability
      was compared. Both stems exhibited similar movement patterns and principally
      moved distally with a retroversional twist. Although elastic movements were
      comparable, the metaphyseal stem exhibited higher plastic deformations than the
      meta-diaphyseal stem, particularly for the metaphyseal, medio-lateral and antero
      posterior components. Under physiological-like loading, the metaphyseal stem
      allowed higher interface movements and tended to initially migrate faster than
      the meta-diaphyseal stem and then stabilized. Elastic movements were comparable
      and seemed to be less influenced by the anchoring concept than by the mechanical
      properties of the bone. The analyses emphasize the importance of metaphyseal bone
      in proximal anchorage and the necessity of an accurate canal preparation to
      prevent excessive initial migration.

PMID- 16429943
TI  - [Initial stability of press-fit acetabular cups--an in-vitro study].
AB  - AIM OF THE STUDY: Mechanical lever-out tests were performed in vitro to
      investigate the initial stability of press fit acetabular cups. METHOD: Five
      different uncemented, hemispherical press-fit cups were implanted in a
      standardized manner into Sawbones, Polyurethane foam blocks. Each cup was levered
      out by using a 250 mm stainless steel rod, which was connected to the acetabular
      cup. Loads were then applied to the rod causing the cup to be diplaced. Lever-out
      forces were recorded by a computer. RESULTS: The results of the lever-out forces
      ranged between 39,2 and 50,8 Nm. The highest initial stability was achieved by
      two Titanium cups with a Titanium plasmaspray coating, a flattened pole and a
      sharp equatorial edge. According to our trials the equatorial rim of the
      polyurethane cavity is the crucial area for the implant's initial stabilty. There
      the highest amount of attrition was observed. CONCLUSION: To guarantee a high
      reproducibilty of the tests it is essential to pay particular attention to the
      quality of the polyurethane foam blocks, to the exactness of the reaming
      procedure and to a defined cup insertion. However as our trials were carried out
      under optimized labaratory conditions one must be careful not to over-interpret
      its results. Intraoperatively primary stability is also influenced by the quality
      of the bone.

PMID- 16429944
TI  - [Residual particle free rough surfaces after rough blasting with steel grit in
      total hip arthroplasty].
AB  - INTRODUCTION: Several shot peening and grit blasting techniques are used to
      modify the surface in the production of hip endoprostheses. A number of
      publications in maxillo- facial- surgery and orthopedic surgery demonstrated
      significant contamination on alumina blasted surfaces. Latest research studies
      suspected an association between surface contamination and early failure of
      endoprostheses associated with third body wear. Additionally, the European
      standard EN 12010 requires surfaces free of residual particles. The aim of this
      study is to evaluate the effects of rough blasting using steel grit followed by a
      pH dependent cleaning procedures with regard to complying with EN 12010. MATERIAL
      AND METHOD: Ti6Al7Nb rods were rough blasted 1 time using steel grit
      ("Stahldrahtkorn", hardness: 56 HRC; R+K Draht GmbH, Leisnig). All blasting
      procedures were carried out with a special grit blasting device with direct
      pressure. One Ti6Al7Nb rod each was grit blasted with 3 and 4 bar pressure and 10
      rods with 5 bar pressure. Surface roughness was measured by means of Mitutoyo-
      Surftest 301 three times before and after grit blasting. The mean value was
      calculated. A field emission scanning electron microscopy (SEM, LEO 1525) was
      used for the detection of residual particles on the surface of the rods with a
      backscattered electron detector. RESULTS: By rough blasting using steel grit a
      mean roughness of 54,9 microm and a maximum roughness of 61,4 microm could be
      achieved. The surface of all rods showed a considerable contamination with steel
      particles after grit blasting. After the a pH- dependent cleaning procedure a
      residual particle free surface was detected in all samples. DISCUSSION: The
      European standard EN 12010 can be fulfilled using rough blasting with steel grit
      followed by a pH dependent cleaning procedure.

PMID- 16429945
TI  - [Histomorphometric evaluation of bone ingrowth of porous titanium by a computer
      assisted analyzing system].
AB  - The objective of this study was to evaluate the bone ingrowth of a new vacuum
      plasma sprayed titanium surface (vps-ti) in comparison to cs-titanium implants in
      a gottinger minipig model. Fifteen gottinger minipigs each received the two
      implants, vacuum plasma sprayed titanium with a porosity of 50% and a pore size
      of 200 microm (vps-ti) and an implant with a similar porosity but a different
      pore size 500 microm (cs-ti), at the proximal femur metaphysis by press-fit
      technique. The pigs were euthanized at three different postsurgical periods: 4, 8
      and 12 weeks. Each femur was harvested and qualitative (macroscopic and
      microscopic) and quantitative (histomorphometric) histological analysis was done
      on histological slides. The results indicated that there was a difference in bone
      ingrowth between the two implants, whereas the bone ingrowth of vps-ti was
      superior to cs-ti after 4 and 8 weeks healing time. 12 weeks post implantationem
      no statistiscal difference was evident. The pore size of 200 microm seemed
      superior to a pore size of 500 microm. Whether or not these effects lead to a
      better mechanical stability remains unanswered.

PMID- 16429946
TI  - V.A.C. instillation: in vitro model. Part 1.
AB  - The reproducibility of a V.A.C. (Vacuum Assisted Closure) instillation system was
      investigated by means of an in vitro model. The relation between the volume of a
      delivered solution and its removal from the system was studied in foams of
      various size. The relationship of instillation time periods and the volume of
      delivered solution was determined.

PMID- 16429947
TI  - Heart tissue viability monitoring in vivo by using combined fluorescence,
      thermography and electrical activity measurements.
AB  - A prototype system for in vivo monitoring of the heart tissue viability by using
      combined measurements of fluorescence, thermography and electrical activity has
      been elaborated for cardiac surgery. The fluorescence imaging of nicotinamide
      adenine dinucleotide NAD(P)H in the blue light range (lambda=467 nm) by using UV
      light (lambda=347 nm) excitation was used to detect metabolic disturbances. The
      method of the principal component analysis was used for the processing of the
      fluorescence image sequences. Far infrared (lambda=7.5-13 microm) imaging was
      used to evaluate temperature dynamics of the tissue surface during circulation
      disturbances. Evaluation of the epicardial electrogram shape by using continuous
      wavelet transform was used to detect and evaluate ischemia-caused disturbances of
      the electrical activity of the tissue. The combination of temperature,
      fluorescence and electrical activity estimates obtained from synchronically
      registered parameters during the experiments on model systems and experimental
      animals yielded qualitatively new results for the evaluation of cardiac tissue
      viability and enabled to achieve a versatile evaluation of the heart tissue
      viability.

PMID- 16429948
TI  - The wow factor: the best HCI wins every time.

PMID- 16429949
TI  - Ambulatory care in the big picture: completing the HIT puzzle.

PMID- 16429950
TI  - Transforming IT--from expense center to value center.

PMID- 16429951
TI  - Closing the "loop" of clinical performance improvement.

PMID- 16429952
TI  - The new alphabet soup: models of data integration, part 1.

PMID- 16429953
TI  - The "marriage" of information and management systems professionals--was it a
      success?

PMID- 16429954
TI  - The state of informatics training and education for nurses.

PMID- 16429955
TI  - Early experiences with positive patient identification.

PMID- 16429956
TI  - Keys to healthcare outsourcing success.

PMID- 16429957
TI  - Leveraging the benefits of Health Information Technology to support healthcare
      delivery model redesign.
AB  - Uninsured and low income underinsured patients create substantial challenges for
      local healthcare systems, yet their providers are not always included in
      community-wide implementations of health information technology. To address this
      deficit, prototypes of the recently proposed National Health Information Network
      must include providers who care for underserved populations. In 2003, a
      consortium of providers founded the Waterbury Health Access Program (WHAP) to
      implement an electronic medical record (EMR) system that would first address the
      needs of the region's vulnerable underserved patients. It was anticipated that
      lessons learned would be applicable to other patient populations as well. The
      WHAP consortium of competing hospitals and outpatient clinics developed a broad
      based community-wide initiative to include implementing a common EMR system to
      share clinical information across all locations. The design includes 11
      outpatient clinic locations linked to a common data-sharing tool that is
      accessible by each clinic, emergency department and community practitioner
      participating in a local, coordinated charity care program. The collaboration
      required to support community-wide implementations of health information
      technology also can be leveraged to facilitate additional quality improvement
      initiatives.

PMID- 16429958
TI  - Keeping it real--building an ROI model for an ambulatory EMR initiative that the
      physician practices espouse.
AB  - The ambulatory electronic medical record initiative at Magic Valley Regional
      Medical Center (MVRMC) in South Central Idaho underwent a rigorous product
      evaluation process that resulted in one of the market-leading EMR products being
      selected for implementation. MVRMC includes four business entities, including a
      213-bed regional hospital and a 19-practice management services organization.
      Early in the process, the organization viewed buy-in from its physicians as a
      critical success factor. The physicians had been integral to product selection,
      and it was equally important for them to trust the economic model for its
      acquisition-especially because it was likely that they would be asked to put
      "some skin in the game." To make this initiative economically feasible, MVRMC
      received a grant from Agency for Healthcare Research and Quality based on the
      potential impact of the endeavor on healthcare delivery in the region. However,
      because the functional analysis did not result in the selection of the least
      expensive product, the AHRQ grant would only help defray the startup expenses,
      but not ongoing support and maintenance expenses after implementation; these
      costs would be borne by anticipated increases in the practice's revenue or
      reduction in its operating expenses. The ROI model would need to explain how each
      practice, from the single physician specialist to an almost 20-physician family
      practice, could pay for the desirable outcomes discussed during the selection
      phase of the project. The physicians, who had participated in technology
      initiatives in the past, were skeptical that cost-justifying an IT system was
      realistic, even though they recognized the potential benefits it could have on
      the quality and consistency of the care. Because some process standardization
      within and between practices would be needed to use electronic charting
      effectively, it was important that the ROI model did not outweigh the benefits of
      an as-yet untested operational workflow that leveraged interoperability. In
      addition, one of the key benefits of the initiative was the integration of
      ambulatory and inpatient information into a common patient-centric view of care.
      This outcome needed to be appropriately considered in the determination of the
      value of the initiative. To make the ROI model real, the physicians needed to be
      willing to take on the responsibility of delivering on the benefits. This report
      highlights the key aspects of using an ROI model in support of an electronic
      medical system implementation emphasizing improvements in intra-practice
      efficiencies, interoperability between multi-specialty practices and ambulatory
      and inpatient care events for a patient while ensuring that all stakeholders
      consider its mathematical estimates as accurate and achievable in the real world.

PMID- 16429959
TI  - Benefiting from ambulatory EHR implementation: solidarity, six sigma, and
      willingness to strive.
AB  - Ambulatory electronic health record systems have the potential to improve
      healthcare quality. Optimizing the value of EHR implementation requires that
      providers and staff become effective and efficient EHR users so paper charts are
      no longer required or desired. Transitioning from paper charts to EHR systems
      requires new learning, significant effort, and workflow changes associated with
      an initial adverse effect on provider efficiency. This case study describes how
      timely EHR implementation and regular use in a large academic internal medicine
      clinic was encouraged, achieved, and demonstrated. Critical success factors
      included readiness to change, solidarity in EHR use, a commitment to striving,
      and process improvement strategies that used the EHR system to repair suboptimal
      clinic workflows. Observed benefits include improvements in patient access,
      workflow efficiency, communication, decision support use, and financial
      performance. These success factors and implementation strategies may help others
      seeking to encourage greater adoption and use of EHRs.

PMID- 16429960
TI  - Ambulatory EHR functionality: a comparison of functionality lists.
AB  - There is a proliferation of lists intended to define and clarify the
      functionality of an ambulatory electronic health record system. These lists come
      from both private and public entities and vary in terminology, granularity,
      usability, and comprehensiveness. For example, functionality regarding a problem
      list includes the following possible definitions: * "Create and maintain patient
      specific problem lists," from the HL7 Electronic Health Record Draft Standard for
      Trial Use. * "Provide a flexible mechanism for retrieval of encounter information
      that can be organized by diagnosis, problem, problem type," from the Bureau of
      Primary Health Care. * "The system shall associate encounters, orders,
      medications and notes with one or more problems," from the Certification
      Commission on Health Information Technology. * "Displays dates of problems on
      problem list," from COPIC Insurance Co. * "Shall automatically close acute
      problems using an automated algorithm," from the Physicians Foundations HIT
      Subcommittee. This article will compare the attributes of these five electronic
      health record functionality lists and their usefulness to different audiences
      clinicians, application developers and payers.

PMID- 16429961
TI  - Data interchange standards in healthcare IT--computable semantic
      interoperability: now possible but still difficult, do we really need a better
      mousetrap?
AB  - The following article on HL7 Version 3 will give readers a glimpse into the
      significant differences between "what came before"--that is, HL7 Version 2.x--and
      "what today and the future will bring," which is the HL7 Version 3 family of data
      interchange specifications. The difference between V2.x and V3 is significant,
      and it exists because the various stakeholders in the HL7 development process
      believe that the increased depth, breadth, and, to some degree, complexity that
      characterize V3 are necessary to solve many of today's and tomorrow's
      increasingly wide, deep and complex healthcare information data interchange
      requirements. Like many healthcare or technology discussions, this discussion has
      its own vocabulary of somewhat obscure, but not difficult, terms. This article
      will define the minimum set that is necessary for readers to appreciate the
      relevance and capabilities of HL7 Version 3, including how it is different than
      HL7 Version 2. After that, there will be a brief overview of the primary
      motivations for HL7 Version 3 in the presence of the unequivocal success of
      Version 2. In this context, the article will give readers an overview of one of
      the prime constructs of Version 3, the Reference Information Model (RIM). There
      are 'four pillars that are necessary but not sufficient to obtain computable
      semantic interoperability." These four pillars--a cross-domain information model;
      a robust data type specification; a methodology for separating domain-specific
      terms from, as well as binding them to, the common model; and a top-down
      interchange specification methodology and tools for using 1, 2, 3 and defining
      Version 3 specification--collectively comprise the "HL7 Version 3 Toolkit."
      Further, this article will present a list of questions and answers to help
      readers assess the scope and complexity of the problems facing healthcare IT
      today, and which will further enlighten readers on the "reality" of HL7 Version
      3. The article will conclude with a "pseudo-code" argument in favor of the
      adoption of HL7 Version 3, framed by citing the recommendation of the
      Interoperability Consortium for the use of HL7 Version 3 as a critical component
      in the National Health Information Infrastructure.

PMID- 16429962
TI  - Implementation of a Project Management Office (PMO)--experiences from year 1.
AB  - Recognized as an early leader in clinical information systems, the University of
      Illinois Medical Center was challenged to meet the ever-increasing demand for
      information systems. Interviews with key stakeholders revealed unfavorable
      attitudes toward the Information Services department. Reasons given were that
      projects often are not aligned with business strategy, projects are delayed, IS
      itself is a barrier to progress, and a lack of proactive planning precipitates
      crises. Under the leadership of a new CIO, IS began developing a Project
      Management Office, or PMO, to better meet medical center business objectives and
      to more effectively manage technology projects. Successes during the first year
      included comprehensive IT strategic planning. Collaborative relationships were
      established with departmental leaders for planning, prioritizing, budgeting, and
      executing projects. A formal Web-based process for requesting IS projects was
      implemented, project management training was provided, and elements of standard
      project management methodology were implemented. While a framework for effective
      project management was created, significant effort is still required to firmly
      root these new processes within the organizational culture. Project management
      office goals for the second year include implementing a project portfolio
      management tool, refining the benefits methodology, and continuing the
      advancement of the project management methodology.

PMID- 16429963
TI  - PA update: DHHS guidelines for the treatment of HIV infection.

PMID- 16429964
TI  - Case study: an active, 24-year-old woman positive for HIV.

PMID- 16429965
TI  - Case study: a 45-year-old gay man with HIV/HCV co-infection.

PMID- 16429966
TI  - [Security: not that in airports!].

PMID- 16429967
TI  - [Knee replacement].
AB  - Total knee replacement is nowadays a surgical technique that has reached maturity
      and is used as frequently as total hip replacement. It is mainly aimed at
      patients suffering from knee osteoarthrosis when it becomes invalidating and
      painful and does not respond anymore to medical conservative treatment and
      physiotherapy. Long term results are excellent in patients aged over 70 years
      old. They are still amenable to improvement in young patients who are more active
      and who put under stress their implants in a longer and more intense way.
      Infection, loosening and malpositioning of the implants are the most common
      complications.

PMID- 16429968
TI  - [Shoulder prostheses: facts and perspectives].
AB  - The goals of shoulder arthroplasties are: 1) to decrease the pain associated with
      degenerative diseases of the glenohumeral joint and 2) to increase the shoulder
      mobility. Isolated humeral hemiprostheses are indicated for pathology limited to
      the humeral head (fractures, avascular osteonecrosis of the humeral head).
      Anatomical total shoulder prostheses are proposed in cases of diseases involving
      both parts of the glenohumeral joint (osteoarthritis, inflammatory arthritis).
      Reversed total shoulder prostheses (constraint) are reserved for glenohumeral
      arthropathies associated with extensive lesions of the rotator cuff. The main
      complications include the glenoid loosening (total prostheses) and the secondary
      glenoid wear (hemiprostheses).

PMID- 16429969
TI  - [Ankle arthroplasty. Rationale for interfaculty collaboration].
AB  - Arthroplasty has become increasingly popular as a solution for end-stage ankle
      arthrosis. Good results, with a 90% survival rate at ten years, have been
      reported with use of recent prostheses. However, the role of ankle arthroplasty
      needs to be more clearly defined. Due to its particular nature and specific
      biomechanical aspects, the ankle joint presents a real challenge for
      arthroplasty. Patient selection and surgical technique need to be optimized to
      improve long-term results. Careful clinical and biomechanical studies need to be
      conducted to objectively determine the long term benefit in terms of quality of
      life. To better address these points the authors of this manuscript have
      coordinated their expertise in a collaborative approach, so as to optimize
      surgical indications, prosthesis implantation, postoperative rehabilitation and
      research.

PMID- 16429970
TI  - [Surgical indications in spinal trauma].
AB  - Surgical indications in spinal trauma remain a controversial topic. In general,
      unstable cervical injuries such as displaced odontoid fractures, burst fractures
      or tear drop fractures require surgical intervention. Thoracolumbar compression
      injuries without posterior wall involvement or significant kyphosis can be
      treated conservatively. Surgery is indicated in fractures-dislocations and burst
      fractures with significant canal narrowing and/or major kyphosis. The role of
      emergency decompression as well as that of steroids remain uncertain since no
      study to date has convincingly proven their efficacy.

PMID- 16429971
TI  - [Imaging of tumors and tumor-like diseases of the hand].
AB  - Tumors and tumor-like lesions of the hand are more frequently benign lesions.
      Plain film X-rays must be obtained in all patients since they are extensive and
      panoramic. Ultrasound can accurately assess the internal structure of the mass
      and its relation with adjacent nerves and vessels. MRI is particularly sensitive
      to bone marrow and is highly effective in characterizing a wide variety of soft
      tissue conditions. However, CT remains the method of choice for evaluating bone
      involvement of soft tissue tumors and small bone tumors such as osteoid oteoma.
      Where a malignant tumor is considered, thoraco-abdominal and/or bone scintigraphy
      are essential to evaluate the presence of metastatic lesions.

PMID- 16429973
TI  - [The false war of the generics. International common names as a tool of defense
      against fraud].

PMID- 16429972
TI  - [Osteoid osteoma and radiofrequency].
AB  - Osteoid osteoma and radiofrequency Osteoid osteoma relates to a benign skeletal
      neoplasm, smaller than 2 cm in diameter, composed of osteoid, highly vascularized
      connective tissue and surrounded by a ring of bone sclerosis. Its aetiology
      remains unknown. It affects twice more males than female patients and occurs
      usually between 5 and 40 years old. Long bones and spine are the most involved
      areas but the whole skeleton can be involved. Clinical manifestations can include
      local pain (increased at night and decreased by activity) and relief with
      salicylates administration. CT guided radiofrequency ablation of osteoid osteoma
      is in comparison to surgery less invasive, time saving and economic technique
      with excellent long term results.

PMID- 16429974
TI  - [AIDS: stronger than contraceptives, sexual abstinence].

PMID- 16429975
TI  - [Passive smoking (results)].

PMID- 16429976
TI  - [England, her pubs, her "binge drinking"].

PMID- 16429977
TI  - [History of the first partial face transplant].

PMID- 16429978
TI  - [Patient satisfaction, measure of the ethical character of medical acts? About
      the face transplant in Amiens].

PMID- 16429979
TI  - [The era of distortion].

PMID- 16429980
TI  - Magnetic resonance imaging characteristics of the foot in horses with palmar foot
      pain and control horses.
AB  - Palmar foot pain is a common cause of lameness. Magnetic resonance imaging (MRI)
      has the potential to detect damage in all tissues of the equine foot, but an
      understanding of the differences in magnetic resonance (MR) images between feet
      from horses with and without palmar foot pain is required. This study aimed to
      describe MR findings in feet from horses with no history of foot-related
      lameness, and to compare these with MR findings in horses with lameness improved
      by palmar digital local analgesia. Thirty-four limbs from horses euthanized with
      a clinical diagnosis of navicular syndrome (ameness >2 months duration, positive
      response to palmar digital nerve blocks and absence of other forelimb problems)
      (Group L), and 25 feet from age-matched horses with no history of foot pain
      (Group N) were examined. For each anatomic structure, MR signal intensity and
      homogeneity, size, definition of margins, and relationships with other structures
      were described. Alterations in MR signal intensity and homogeneity were graded as
      mild, moderate, or severe and compared between Groups L and N. Results revealed
      that there were significant differences in MR images between Groups N and L.
      Multiple moderate-severe MR signal changes were present in 91% of limbs from
      Group L and moderate (none were graded severe) in 27% of limbs from Group N. In
      most Group L limbs, more than three structures and frequently six to eight
      structures were abnormal. Concomitant abnormalities involved most frequently the
      deep digital flexor tendon, distal sesamoidean impar ligament, navicular bone,
      collateral sesamoidean ligament, and navicular bursa (with significant
      associations in severity grade between these structures), sometimes with
      involvement of the distal interphalangeal joint and/or its collateral ligaments.
      It was concluded that findings on MR images were different between horses with
      and without foot pain, and that pain localized to the foot was associated with MR
      changes in a variety of structures, indicating that damage to several structures
      may occur concurrently and that MR imaging was useful for evaluation of foot
      pain.

PMID- 16429981
TI  - How does magnetic resonance imaging represent histologic findings in the equine
      digit?
AB  - Magnetic resonance (MR) imaging is increasingly used in the diagnosis of equine
      foot pain, but improved understanding of how MR images represent tissue-level
      changes in the equine foot is required. We hypothesized that alterations in
      signal intensity and tissue contour would represent changes in tissue structure
      detected using histologic evaluation. The study objectives were to determine the
      significance of MR signal alterations in feet from horses with and without
      lameness, by comparison with histopathologic changes. Fifty-one cadaver feet from
      horses with a history of lameness improved by palmar digital analgesia (n = 32)
      or age-matched control horses with no history of lameness (n = 19) were stored
      frozen before undergoing MR imaging and subsequent histopathological examination
      at standard sites (deep digital flexor tendon, navicular bone, distal sesamoidean
      impar ligament, collateral sesamoidean ligament, and navicular bursa). Using MR
      images, signal intensity and homogeneity, size, definition of anatomic margins,
      and relationships with other structures were described. Alterations were graded
      as mild, moderate, or severe for each structure. For each anatomic site examined
      histologically the structures were described and scored as no changes, mild,
      moderate, or severe abnormalities, also taking into account adhesion formation
      within the navicular bursa detected on macroscopic examination. Alterations in MR
      signal intensity were related to changes at the tissue level detected by
      histologic examination. A sensitivity and specificity comparison of MR imaging
      with histologic examination was used to evaluate the significance of MR signal
      alterations for detection of moderate-to-severe lesions of the deep digital
      flexor tendon (DDFT), navicular bone, distal sesamoidean impar ligament (DSIL),
      collateral sesamoidean ligament (CSL) and navicular bursa. Agreement between the
      MR and histologic grading was assessed for each structure using a weighted kappa
      agreement. Direct comparison between histology and MR imaging for individual
      limbs revealed that signal alterations on MR imaging did represent tissue-level
      changes. These included structural damage, fibroplasia, fibrocartilaginous
      metaplasia, and hemosiderosis in ligaments and tendons; trabecular damage,
      osteonecrosis, fibroplasia, cortical defects, and increased vascularity in bone;
      and fibrocartilage defects. MR imaging had a high sensitivity and specificity for
      most structures. MR imaging had high specificity for lesions of the DDFT, CSL and
      navicular bursa, quite high specificity for lesions of the medulla of the
      navicular bone and its proximal aspect, with moderate specificity for the DSIL,
      and distal, dorsal and palmar aspects of the navicular bone, and was sensitive
      for detection of abnormalities in all structures except the dorsal aspect of the
      navicular bone. When MR and histologic grades alone were compared, there was good
      agreement between MR and histologic grades for the navicular bursa, DDFT,
      navicular bone medulla and CSL; moderate-to-good agreement in grades of the
      distal and palmar aspects of the navicular bone; fair to moderate in grades of
      the DSIL, and poor agreement for the dorsal and proximal aspects of the navicular
      bone. The results of this study support our hypothesis and indicate the potential
      use and limitations of MR imaging for visualization of structural changes within
      osseous and soft tissue structures of the equine foot.

PMID- 16429983
TI  - A lumbosacral transitional vertebra in the dog predisposes to cauda equina
      syndrome.
AB  - The association between the occurrence of a lumbosacral transitional vertebra
      (LTV) and the cauda equina syndrome (CES) in dogs was investigated. In 4000
      control dogs without signs of CES, 3.5% had an LTV, while in 92 dogs with CES,
      16.3% had an LTV. The lesion causing CES always occurred between the last true
      lumbar vertebra and the LTV. Dogs with an LTV were eight times more likely to
      develop CES than dogs without an LTV. German Shepherd dogs were eight times more
      likely to develop CES compared with other breeds. Male dogs were twice as likely
      to develop CES than females. Dogs with an LTV develop CES 1-2 years earlier than
      dogs without an LTV.

PMID- 16429982
TI  - Lumbosacral transitional vertebrae in dogs: classification, prevalence, and
      association with sacroiliac morphology.
AB  - The prevalence of lumbosacral transitional vertebrae (LTV) was determined by
      reviewing the pelvic radiographs of 4000 medium- and large-breed dogs of 144
      breeds routinely screened for canine hip dysplasia. An LTV was seen in 138 (3.5%)
      dogs. The prevalence was higher in German Shepherd dogs and Greater Swiss
      Mountain dogs than in the other breeds, suggesting a genetic predisposition.
      There was no gender predisposition. The transverse processes of the LTV were
      divided into three types based on their morphological characteristics: lumbar
      type or type 1; intermediate type or type 2; and sacral type or type 3. In a
      symmetric LTV, both transverse processes are of the same type, while in an
      asymmetric LTV they are not. The frequency of occurrence of symmetric and
      asymmetric LTV was similar. In symmetric LTV, intermediate-type transverse
      processes predominated. Most of the asymmetric LTV had an intermediate-type
      transverse process combined with a lumbar or sacral type, respectively. Highly
      asymmetric LTV were often angled relative to the adjacent vertebrae. We
      hypothesize that an LTV is not the result of transformation of a lumbar into a
      sacral vertebra or vice versa, but rather is an autonomous intermediate type of
      vertebra. It occurs when the point of contact of the pelvis with the vertebral
      column is slightly cranial or caudal to its normal position. The resulting
      formative stimulus on the vertebral ossification centers, sagittally still
      separated, causes the various morphologies seen in LTV including the asymmetric
      variations.

PMID- 16429984
TI  - Comparative performance of radiography and computed tomography in the diagnosis
      of middle ear disease in 31 dogs.
AB  - The purpose of this study was to compare computed tomography (CT) and radiography
      for diagnosing the presence and severity of middle ear disease in dogs with a
      history of chronic otitis externa. Thirty-one dogs undergoing a total ear canal
      ablation and bulla osteotomy were studied. Three normal dogs served as controls.
      All dogs were examined using radiography and CT. Three radiologists independently
      evaluated imaging studies in random order. A visual analog scale method was used
      for scoring certainty and severity of middle ear disease. Surgical findings were
      recorded intra-operatively. Bulla lining samples were submitted for
      histopathologic evaluation and scored by a single pathologist who also used a
      visual analog scale system. Findings from both imaging modalities agreed more
      closely with surgical findings than with histopathologic findings. With either
      surgical or histopathologic findings as the gold standard, CT was more sensitive
      than and as specific as radiographs for predicting presence and severity of
      middle ear disease. Observer performance with CT was more consistent than the
      performance with radiographs in the detection of changes that occur with middle
      ear disease. Both radiography and CT were more accurate for predicting the
      severity of the disease than its presence. Findings indicate that CT is more
      accurate and reliable than radiography in diagnosing middle ear disease for dogs
      having concurrent otitis externa, but only when severity of disease is moderate
      or high. With low severity of disease, diagnostic certainty for both modalities
      becomes more variable.

PMID- 16429985
TI  - Computed tomography-anatomy of the normal feline nasolacrimal drainage system.
AB  - Computed tomography (CT) of the nasolacrimal drainage system with and without
      contrast medium (barium sulfate) was used to create an anatomic basis for
      clinical evaluation in domestic cats. To evaluate and compare the anatomical
      findings, three casts were carried out and were followed by CT examinations.
      These CT series were also used for a three-dimensional (3D) reconstruction of the
      nasolacrimal drainage system within surrounding structures. In noncontrast CT
      images, osseous structures limiting the nasolacrimal drainage system are easily
      recognizable. In most cats, this allows the identification of the nasolacrimal
      drainage system even without contrast enhancement. A distal part of the lacrimal
      sac adjoins directly to the respiratory mucosa of the nasal cavity without an
      osseous protection. Thus, this may represent a predilection site for infiltration
      of adjacent pathologic processes from the nasal cavity onto the lacrimal sac. The
      nasolacrimal duct begins on level with the maxillary third premolar tooth. The
      apex of the root of the canine tooth is situated very close to the nasolacrimal
      duct. This close topographic relation may lead to problems with the nasolacrimal
      drainage system. In domestic cats the nasolacrimal drainage system consists of a
      descending and a horizontal part, which form an angle of approximately 90 degrees
      for unhindered drainage of the lacrimal fluid.

PMID- 16429986
TI  - The effect of positioning on the appearance of selected cranial thoracic
      structures in the dog.
AB  - In this retrospective study the effect of thoracic positioning on the visibility
      and size of selected cranial thoracic structures in dogs was investigated.
      Dorsoventral (DV), ventrodorsal (VD) as well as left lateral recumbent (LLR) and
      right lateral recumbent (RLR) thoracic radiographs of 17 large, 15 medium, and 10
      small skeletally mature dogs were evaluated. The craniodorsal and cranioventral
      mediastinum, the cupula pleura and sternal lymph nodes were examined. The effect
      of obesity was also evaluated. The craniodorsal mediastinum was better delineated
      on DV radiographs and was wider on VD radiographs. The craniodorsal mediastinal
      width: width of T2 cranial end-plate on VD radiographs was 2.41 for all groups
      combined and obesity significantly influenced this value. The cranioventral
      mediastinum was more visible in RLR and VD radiographs. A normal sternal lymph
      node soft tissue opacity was seen most commonly in RLR in large breed dogs and
      had a mean length of 30 mm. The pulmonary cupula extended beyond the first rib on
      all views and extended more cranially and was better visualised on VD than DV
      views.

PMID- 16429988
TI  - Calvarial hyperostosis syndrome in two bullmastiffs.
AB  - Two bullmastiffs with calvarial hyperostosis syndrome are described and are the
      first documented examples in females. The clinical and radiologic features were
      similar to those previously reported in males. Magnetic resonance (MR) imaging
      findings have not previously been reported. One dog underwent MR imaging and
      abnormalities included thickening of the frontal bones with loss of normal fat
      signal and changes in the overlying soft tissues. In one of the dogs, long bone
      changes were seen in the femora and resembled those seen with craniomandibular
      osteopathy.

PMID- 16429987
TI  - Imaging diagnosis: mineralization of the aorta, celiac and cranial mesenteric
      arteries in a cat with chronic renal failure.

PMID- 16429989
TI  - Magnetic resonance imaging characteristics of ascending hemorrhagic myelomalacia
      in a dog.
AB  - A 4-year-old neutered female terrier-cross was evaluated for an acute onset of
      paraplegia. Utilizing magnetic resonance (MR) imaging, the cause of the
      neurologic deficits was determined to be a lumbar intervertebral disc extrusion.
      The MR study additionally demonstrated parenchymal hyperintensity on T2-weighted
      images and similarly located diffuse hypointensity on gradient echo images,
      cranial and caudal to the compressive extradural lesion. Hemorrhagic myelomalacia
      was suspected based on these MR characteristics, which was subsequently confirmed
      surgically and histopathologically.

PMID- 16429990
TI  - Smooth muscle neoplasia of the urinary bladder wall in three dogs.
AB  - Smooth muscle origin neoplasia of the urinary bladder wall is rare in dogs. This
      report describes the ultrasonographic features of two bladder wall leiomyomas and
      one bladder wall leiomyosarcoma. All three dogs had a single, smoothly
      marginated, round, hypo to mixed echogenicity intraluminal mass in the urinary
      bladder. Based on color Doppler examination of the masses, there was no visible
      blood flow.

PMID- 16429991
TI  - Echocardiographic evidence of an aortico-pulmonary septal defect in a 4-day-old
      thoroughbred foal.
AB  - We describe the echocardiographic findings in a 4-day-old thoroughbred foal with
      an aortico-pulmonary septal defect. The foal had labored breathing, cyanotic
      mucous membranes and a continuous grade 5/6 heart murmur with point of maximal
      intensity over the base of the heart on the right side. Echocardiographically,
      there was a large communication between the aorta and the pulmonary artery just
      dorsal to the base of the heart. The cardiac anomaly seen during the
      echocardiographic exam was confirmed at necropsy where a large communication
      between the two great vessels was observed. These findings correlate with
      previous studies in humans, dogs, and cats. The possible failure in the
      embryologic development that led to this unusual cardiac anomaly is discussed.

PMID- 16429992
TI  - Radiographic and ultrasonographic findings of emphysematous cystitis in four
      nondiabetic female dogs.
AB  - The urinary bladder of four dogs with emphysematous cystitis was assessed
      radiographically. Ultrasonography was also performed using a 7.5-MHz microconvex
      probe in dorsal recumbency and in a standing position. Ultrasonographically there
      were bright echoes and reverberations typical of gas in all dogs. This was
      entrapped in the bladder wall as it appeared in the same location in recumbent
      and standing positions. Bladder size was reduced and bladder content was
      echogenic in all dogs. In only one out of the four dogs was a gas stripe seen in
      the bladder on radiographs. Proteus mirabilis was isolated from the urine of all
      patients. Diabetes was ruled out on the basis of urine and blood analysis. A
      small amount of gas can be difficult to detect on radiographs. Ultrasonography
      appears to be a more sensitive technique for detection of gas within the bladder
      at an early stage of emphysematous cystitis. Prevalence of emphysematous cystitis
      may be underestimated if only radiographs are made.

PMID- 16429993
TI  - Ultrasonographic evaluation of the external ear canal and tympanic membrane in
      dogs.
AB  - Ultrasonographic imaging of the canine external ear canal, tympanic membrane, and
      tympanic bulla was described in five healthy beagle dogs before and after
      infusion of saline into the ear canal. Saline served as an acoustic window. With
      this method, the external ear canal, and tympanic bulla were visible in the same
      imaging plane and the integrity of the tympanic membrane could be evaluated
      indirectly by confirming an intact tympanic membrane, which appeared at the end
      of the ear canal as a hyperechoic line with reverberation. Experimentally,
      perforated tympanic membrane could be evaluated by identifying anechoic saline in
      the tympanic bulla lumen. The air and fluid-filled tympanic bulla were also
      visualized. Ultrasonography with saline as an acoustic window appears to be
      helpful for the evaluation of the external ear canal, tympanic membrane, and
      tympanic bulla and it may have the potential to be a useful clinical tool in
      evaluation of integrity of the tympanic membrane.

PMID- 16429994
TI  - Intraoperative spinal ultrasonography in two dogs with spinal disease.
AB  - Ultrasonography was performed during spinal surgery on two dogs that were
      suspected of having intramedullary lesions by myelography and magnetic resonance
      imaging. Ultrasonographically, the pathologic conditions of the spinal canal or
      cord were adequately imaged during surgery in both dogs. On the basis of
      ultrasonographic findings, a biopsy was obtained in Patient 1 and removal of the
      lesion was accomplished in Patient 2. Histopathologic diagnosis was myelomalacia
      in Patient 1 and spinal nephroblastoma in Patient 2. Intraoperative
      ultrasonography was demonstrated to be suitable for detecting intradural
      conditions, and, thus, is valuable for increasing the accuracy of biopsies or
      completeness of resections of intramedullary lesions.

PMID- 16429996
TI  - "Le Grand Derangement": nursing education in Louisiana after the hurricanes.

PMID- 16429995
TI  - Evaluation of 99MTC-diethylenetriaminepentaacetic acid renal scintigram curves in
      normal dogs after induction of diuresis.
AB  - The normal 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigram curve
      has 3 distinct phases; an arterial phase followed by progressive uptake and
      subsequent excretion from the kidney. In dogs with X-linked hereditary nephritis,
      a distinct flattening of the renal scintigram curve has been observed prior to
      any decline in glomerular filtration rate (GFR). The cause of this shape change
      is not known, however, it coincided with decreased urine-specific gravity and
      thus might be related to polyuria. To further evaluate this possibility, we
      assessed whether diuresis without concurrent renal disease could flatten the
      99mTc-DTPA renal scintigram curve. GFR scintigraphy was performed in six healthy
      dogs once as a baseline, and again after induction of diuresis by each of four
      different methods. Scintigram curves were evaluated subjectively as well as
      quantitatively by calculation of GFR estimates, mean renal transit times, time to
      peak activity and half-time clearance. Complete flattening of the renal
      scintigram curve did not occur with diuresis alone, and therefore, flattening of
      the scintigram curve may serve as an early indicator of renal dysfunction.
      However, during diuresis after intravenous saline administration, alterations in
      time to peak activity and mean renal transit time may create inaccuracies in GFR
      estimates based on the conventional regression formula that cause a false
      lowering of the resultant global GFR value.

PMID- 16429997
TI  - Faculty matters. Diane J. Skiba.

PMID- 16429999
TI  - Challenging traditional teaching and learning paradigms: online learning and
      emancipatory teaching.
AB  - The thoughts and expectations of faculty leaving the traditional classroom for
      online teaching are explored. This article discusses teaching strategies and
      technological advances and how these are affected by changing philosophical
      viewpoints about nursing and education. Basic issues involving technology and
      education focus on a variety of issues including the ability of the learner to
      grow existentially.

PMID- 16429998
TI  - Emergency preparedness curriculum in nursing schools in the United States.
AB  - With concern about bioterrorism and inadequacies in responding to mass casualty
      events, health care professionals have been placed in the category of first
      responders. The International Nursing Coalition for Mass Casualty Education
      (INCMCE) was established to plan strategically to address the educational needs
      of the nation's nurses. This study sought to determine the types and levels of
      disaster preparedness curricula being delivered or in development in nursing
      programs at all levels. INCMCE surveyed 2,013 deans or directors of nursing
      schools as to curricula for emergency preparedness prior to September 11, 2001,
      and during the two following academic years. Initial requests were sent via email
      and the US postal service. Respondents were invited to answer the online survey
      so data could be directly entered into a database for purposes of data analysis.
      Responses were received from 348 schools of nursing. Curriculum plans, followed
      by competency lists, were selected as most helpful for teaching content in
      disaster preparedness. The survey results validated the general assumption that
      nursing programs provide limited curricula in this area. The mean number of hours
      of disaster preparedness content provided, approximately four hours, did not
      change significantly over three academic years. The study also showed that 75
      percent of respondents thought that nurse faculty were inadequately prepared in
      the area of disaster management. The study established a baseline for future
      curricular growth.

PMID- 16430000
TI  - Impact of technology on the content and nature of teaching and learning.
AB  - Excelsior College has a Web-based graduate nursing program with a focus on
      clinical systems management and health care informatics that incorporates a
      variety of technology-based educational strategies: synchronous and asynchronous
      collaborative communication, project/activity-based learning, and web-based
      interaction and feedback. This pilot study was undertaken to examine the
      relationship between the use of technology and outcomes in two computer-mediated
      courses in the program. Questionnaires, interviews, standardized scales, and
      course assessments were selected or developed as needed, and existing demographic
      information and evaluations were accessed for comparison purposes. The analysis
      strategy was specific to the data, the sample size, and the types of questions
      posed. The tools developed for and used in the study can be applied across the
      curriculum to enhance evaluation of learning and program effectiveness.

PMID- 16430001
TI  - Fostering the scholarship of discovery and integration for advanced practice
      education.
AB  - Graduate faculty are challenged to foster the scholarship of discovery and
      integration in their students. Fostering this scholarship requires that faculty
      critically analyze their approach to teaching and learning with the ultimate goal
      of helping students grow exponentially in ways that will continue after
      completion of their course or class. This article describes a course activity
      designed to enhance students' abilities to read, critique, and apply literature
      from multiple scientific disciplines to a clinical realm while maintaining their
      focus on their health-related scientific discipline. Applied to a course in
      advanced pathophysiology, the course activity described is amenable for adoption
      to multiple graduate-level courses and encourages individual, collective, and
      practice-specific growth.

PMID- 16430002
TI  - Self-regulated learning during a clinical preceptorship: the reflections of
      senior baccalaureate nursing students.
AB  - This research was conducted to test the efficacy of audiotapes as a method of
      recording reflections of senior baccalaureate nursing students in a clinical
      preceptorship. The over-all aim of the research was to promote cognitive and
      metacognitive thinking processes with self-regulated learning strategies for
      problem solving in clinical situations. Verbal protocol technique revealed a
      consistent use of self-regulated learning strategies with a focus on
      environmental structuring for metacognitive activities. Common themes of thought
      were found in both clinical experiences and the use of critical thinking skills.

PMID- 16430003
TI  - Patient care simulations: role playing to enhance clinical understanding.
AB  - Role-play techniques can serve as an effective substitute for, and supplement to,
      simulation technology when teaching clinical nursing skills. They provide risk
      free opportunities to practice clinical skills and develop clinical judgment. A
      two-phase patient care simulation, performed in real time, is described. Students
      are presented with a scenario and work cooperatively in role-playing appropriate
      care, with one student using a prepared script to assume the role of patient. The
      class functions as a resource for four students who assume the nursing role.
      Students reported increased understanding of course material as a result of
      participation in the clinical simulation scenario. Faculty observed a decreased
      failure rate on the corresponding course examination.

PMID- 16430004
TI  - Distance education: a strategy for leadership development. 1995.

PMID- 16430006
TI  - Globalization in dentistry?

PMID- 16430005
TI  - The millennials: have they arrived at your school of nursing?

PMID- 16430007
TI  - Evaluating a method of artificially hypermineralizing dentin to simulate natural
      conditions in bonding studies.
AB  - PURPOSE: This study tested an in vitro model of dentin hypermineralization,
      aiming to simulate naturally hypermineralized dentin for bond strength studies.
      The effect on bond strength of a double-etching treatment on the artificially
      hypermineralized substrate was also evaluated. MATERIALS AND METHODS: Extracted
      human third molars were selected and 2 groups were formed: a group of 3 teeth,
      called N (normal dentin) and a group of 6 teeth, called H (hypermineralized
      dentin). Occlusal surfaces were ground flat to expose midcoronal dentin. Group H
      was subjected to artificial hypermineralization and subdivided into 2 subgroups:
      Ht and Hd. The exposed dentinal surfaces of group N and subgroup Ht were etched
      with 37% phosphoric acid for 15 s prior to bonding with Single Bond adhesive.
      Dentin of the subgroup Hd was etched twice (double etching) prior to bonding with
      Single Bond. A 4-mm-high Z100 composite buildup was created on each tooth and,
      after 24 h water storage, bond strengths were evaluated by the microtensile
      method. The data between group N and subgroup Ht and between subgroups Ht and Hd
      were compared using the Student's t test (alpha = 0.05). RESULTS: No significant
      difference was observed between bond strengths of group N and subgroup Ht (p =
      0.108). Subgroup Hd was statistically different from Ht (p < 0.0001).
      CONCLUSIONS: Bond strengths of Single Bond to artificially hypermineralized
      dentin did not differ statistically from those to normal dentin substrate. The
      double etching approach significantly reduced bond strengths of artificially
      hypermineralized dentin.

PMID- 16430008
TI  - Bonding of single-component adhesives to dentin following chemomechanical caries
      removal.
AB  - PURPOSE: To determine the effect of chemomechanical caries removal on the bonding
      quality of contemporary single-component adhesives to dentin. MATERIALS AND
      METHODS: N-monochloro-DL-2-aminobutyrate solution (NMAB) and Carisolv gel were
      used to chemomechanically remove dentin caries in 60 extracted human molars.
      Caries removal with rotating instruments served as the control. Two single
      component adhesive systems, Syntac Single Component and Excite, were applied to
      bond the hybrid composite Tetric Ceram to the treated dentin surfaces. The
      prepared samples were sectioned for microtensile bond strength testing and SEM
      examination of the bonding interfaces. The debonding patterns of the fractured
      samples were also assessed. RESULTS: No statistically significant differences
      were found between the bond strengths of either adhesive to the conventionally
      and the NMAB-treated dentin (p > 0.05). However, the Carisolv-treated dentin
      yielded significantly higher (p > 0.05) bond strength values with both adhesives
      compared to those on dentin prepared with rotating instruments. No statistical
      difference could be discerned between the 2 adhesive systems (p > 0.05), nor was
      the interaction between the 2 variables under investigation (method of caries
      removal and the type of adhesive) statistically significant (p = 0.7712). SEM
      images indicated unspecific effects of the tested variables on both the thickness
      of the hybrid layer and the length of the resin tags. CONCLUSION: Under the
      conditions of this study, using the Carisolv chemomechanical caries removal
      system to prepare dentin surfaces enhanced the dentin/adhesive bond strength. In
      addition, the chemical nature of the adhesive systems seems to have no effect on
      the values of bond strength.

PMID- 16430009
TI  - Effect of tooth age on microtensile bond strength of two fluoride-releasing
      bonding agents.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of age of dentin
      and enamel on the microtensile bond strengths of a glass-ionomer based, all-in
      one, single-step, self-etching adhesive system (Reactmer Bond, RB) and an
      antibacterial, two-step self-etching primer system (ABF Bond, ABF). MATERIALS AND
      METHODS: Extracted molars from 3 age groups (20 to 25, 35 to 40, and 50 to 55
      years) were used. Enamel was removed from the occlusal surfaces of the teeth, and
      the entire flat surfaces were covered with composite resin (4 mm in height)
      following application of bonding agents. The bonded specimens were thinly
      sectioned parallel to the long axis of the tooth into 0.87 +/- 0.03 mm2
      rectangular sections, resulting in 6 to 7 enamel specimens and 10 to 15 dentin
      specimens per tooth. The specimens were subjected to the microtensile test at a
      crosshead speed of 1 mm/min. The data were analyzed by Univariate ANOVA, Tukey
      HSD, and regression analysis. RESULTS: The bond strength of ABF to both enamel
      and dentin was higher than the bond strength of RB. Bond strengths of ABF to
      dentin were significantly higher than the bond strengths to enamel (p < 0.05).
      The 35- to 40-year age group of ABF showed the highest bond strength of all. In
      RB dentin groups, 34% of specimens showed cohesive failure in composite resin
      material. CONCLUSION: Bond strength values to enamel were not affected by age of
      teeth in either bonding system. Dentinal bond strength using ABF changed
      according to age of the teeth. Age did not affect bond strength values of RB to
      dental hard tissues. However, the high number of cohesive failures in Reactmer
      paste indicated low tensile strength of the material.

PMID- 16430010
TI  - Microtensile bond strength of current dentin adhesives measured immediately and
      24 hours after application.
AB  - PURPOSE: To evaluate the immediate microtensile bond strengths achieved with
      representative adhesive systems from each of the four current bonding approaches.
      MATERIALS AND METHODS: Resin composite was bonded incrementally to flat,
      midcoronal dentin from 33 human molars, using the adhesives (Adper Scotchbond MP;
      Adper Scotchbond 1; Optibond Solo Plus; Clearfil SE Bond; AdheSE; Tyrian SPE +
      One Step Plus; Optibond Solo Plus self-etching; One-Up Bond F; iBond; Adper
      Prompt L-Pop; Xeno III) according to the respective manufacturer's instructions.
      The bonded specimens were immediately sectioned into sticks and underwent
      microtensile bond testing either immediately or after 24 h. Data were analyzed
      with two-way ANOVA and LSD tests. RESULTS: No significant differences were found
      between immediate and 24-h bond strengths (p > 0.05). However, significant
      differences were observed among adhesives (p = 0.001). The all-in-one adhesive
      iBond showed statistically lower values when compared to all the other adhesives.
      Adper Prompt L-Pop, Xeno III, Tyrian SPE + One Step Plus and One-Up Bond F, all
      self-etching adhesives, were significantly weaker than AdheSE, Optibond Solo
      Plus, Adper Scotchbond 1, Optibond Solo Plus self-etching, Clearfil SE Bond, and
      Adper Scotchbond MP, which did not differ statistically from each other.
      CONCLUSION: Microtensile bond strengths of representative adhesive systems from
      the four categories of bonding agents were not equivalent, with the lowest values
      recorded for the one-step self-etching adhesives. There were no differences in
      the bond strengths when measured immediately and after 24 h.

PMID- 16430012
TI  - The effects of soft-start vs continuous-light polymerization on microleakage in
      Class II resin composite restorations.
AB  - PURPOSE: Despite the different light sources and polymerization techniques
      developed to eliminate it, microleakage of resin composite still remains a
      problem. This in vitro study was designed to compare the effects of exponential
      mode soft-start polymerization with those of standard and high-intensity
      continuous light polymerization on microleakage in Class II resin composite
      restorations. MATERIALS AND METHODS: Standardized Class II cavities (4 mm wide, 4
      mm long, 5 to 6 mm high, 2 mm deep) were prepared in 50 extracted human molars.
      Specimens were divided into 5 groups (n = 10) and restored using the same hybrid
      resin composite (Z250), but separately polymerized by one of five different
      methods: group 1: continuous halogen light polymerization for 40 s; group 2:
      continuous high-intensity halogen light polymerization for 10 s; group 3:
      exponential mode soft-start halogen light polymerization for a total of 40 s;
      group 4: continuous LED light polymerization for 40 s; Group 5: exponential mode
      soft-start LED light polymerization for a total of 40 s. All specimens were
      thermocycled for 1000 cycles at 5 degrees C to 55 degrees C and then placed in
      0.5% basic fuchsin dye for 24 h. Specimens were then rinsed, embedded in resin
      and sectioned longitudinally. Dye penetration at occlusal and cervical margins
      was rated using a scale of 0 to 4. Data was analyzed using Kruskal-Wallis and
      Mann-Whitney U-tests. RESULTS: Significantly lower marginal leakage was recorded
      with exponential mode soft-start polymerization when compared to continuous light
      polymerization. No significant differences in microleakage were observed between
      LED and halogen light polymerization. CONCLUSION: Within the limits of this in
      vitro study, the use of the soft-start exponential mode of LED and/or halogen
      light units in the polymerization of hybrid composite was found to produce
      significantly lower microleakage at both occlusal and cervical margins when
      compared to continuous light polymerization methods.

PMID- 16430011
TI  - Effect of insertion technique and adhesive system on microleakage of Class V
      resin composite restorations.
AB  - PURPOSE: To evaluate the effect of different insertion techniques and adhesive
      systems on microleakage of Class V composite resin restorations. MATERIALS AND
      METHODS: Forty-eight human molars were randomly assigned to four groups (n = 12).
      Standardized mixed Class V cavities (enamel and dentin margins) were prepared at
      the CEJ. A total-etch (Adper Scotchbond MultiPurpose) and a self-etching (iBond)
      adhesive system were evaluated using either an incremental or single-step (bulk)
      insertion technique. The preparations were restored with Esthet*X micromatrix
      hybrid composite. The teeth were thermocycled 1000 cycles, immersed in 1%
      methylene blue dye for 24 h, and invested in acrylic resin. The specimen blocks
      were then sectioned longitudinally, with dye penetration (microleakage) examined
      with a 20X binocular microscope. Enamel and dentin margins were scored separately
      for microleakage using an ordinal ranking system. Results were analyzed using non
      parametric tests at a p < 0.05 level of significance. RESULTS: Significance was
      exhibited between the groups (adhesive material/insertion technique) at the
      coronal and apical margins. At the coronal margin, the total-etch
      adhesive/incremental insertion group exhibited significantly less leakage than
      the other groups, while at the apical margin, the total-etch adhesive/incremental
      insertion group showed significantly less leakage than the self-etching
      adhesive/bulk insertion group. Significantly less leakage was found at the
      coronal margins compared to the apical margins of the material/technique groups.
      CONCLUSION: The use of a total-etch adhesive system and incremental insertion of
      composite significantly reduced microleakage at the coronal and apical margins of
      Class V composite restorations.

PMID- 16430013
TI  - Antibacterial activity of two adhesive systems using various microbiological
      methods.
AB  - PURPOSE: To compare the antibacterial activities of two dentin bonding systems
      (DBS), Clearfil Protect Bond and Xeno III, by agar well, paper and dentin disks,
      and a cavity tooth model. MATERIALS AND METHODS: For the well technique, the test
      materials were filled in the agar wells inoculated with Streptococcus mutans
      (ATCC 25175). The paper disks were embedded in adhesives and placed on the seeded
      agar plates for the second technique. The adhesives were applied on the dentin
      disks and placed in holes in the plates for the third technique. After 48 h, the
      zones of inhibition were measured. In the cavity tooth model test, 3 cavities
      were prepared in the flat occlusal dentin of extracted human molars. The teeth
      were left in S. mutans for 72 h to allow bacterial invasion. The DBS were applied
      in the same manner as in clinical application on each of the two infected
      cavities and the third was left unapplied for control. The teeth were kept in
      saline for 72 h. Standard amounts of dentin chips were obtained from the cavity
      walls and the number of bacteria recovered was counted. RESULTS: The results were
      analyzed by factorial ANOVA and Dunnett C test. Clearfil Protect Bond primer
      exhibited the greatest inhibition zones followed by Consepsis and unpolymerized
      Xeno III in all the techniques tested (p < or = 0.05). Clearfil Protect Bond
      resulted in significantly less bacterial recovery than Xeno III by the tooth
      cavity method (p < or = 0.05). CONCLUSION: Clearfil Protect Bond was found to be
      the most antibacterial material with all the techniques used. Furthermore,
      Clearfil Protect Bond was able to inactivate the bacteria in the cavity more
      effectively than Xeno III.

PMID- 16430014
TI  - Effect of polymerization shrinkage on the sealing capacity of resin fillers for
      endodontic use.
AB  - PURPOSE: Recently, highly flowable resin fillers have been proposed for filling
      root canals using a single-cone approach. The purpose of this study was to test
      the hypothesis that polymerization shrinkage, which is inherent to this type of
      filler, can break the close initial contact between the main core and the
      surrounding dentin even if root dentin infiltration has occurred. MATERIALS AND
      METHODS: Twenty roots of anterior teeth were prepared chemomechanically and
      divided into 4 groups of 5 samples each. Groups 1 and 2: hydrophilic resin filler
      injected and spread, roots sectioned after setting; group 3: hydrophilic resin
      filler injected and spread, dental substrate dissolved after setting; group 4:
      hydrophobic resin sealer lentulo-spiraled and spread, roots sectioned after
      setting (as control). In groups 1, 2, and 3 the material was used following
      manufacturer's instructions. The section surfaces of groups 1 and 4, and the
      resin components of group 3 were processed for conventional FE-SEM. The section
      surfaces of group 2 were observed successively under environmental and high
      vacuum conditions. RESULTS: Microscopic examination of the resin-dentin
      interfaces of groups 1 and 2 showed the existence of resin-dentin interdiffusion
      zones (RDIZ); however, the close initial contact between the main core and the
      surrounding dentin was often lost. In group 3, resin tag morphology was well
      characterized. Identical morphological features were observed in the resin-dentin
      interfaces in group 4. CONCLUSION: Since the existence of resin tags did not
      exclude the existence of a gap between the main core and the adjacent RDIZ, our
      results confirmed the proposed hypothesis.

PMID- 16430015
TI  - The effect of adhesive systems on the pullout strength of a fiberglass-reinforced
      composite post system in bovine teeth.
AB  - PURPOSE: To evaluate the pullout strength of a glass fiber-reinforced composite
      post (glass FRC) cemented with three different adhesive systems and one resin
      cement. The null hypothesis was that pullout strengths yielded by the adhesive
      systems are similar. MATERIALS AND METHODS: Thirty bovine teeth were selected.
      The size of the specimens was standardized at 16 mm by sectioning off the coronal
      portion and part of the root. The specimens were divided into three groups,
      according to the adhesive system, which were applied following the manufacturers'
      instructions: G1, ScotchBond Multi-Purpose Plus; G2, Single Bond; G3, Tyrian
      SPE/One-Step Plus. The glass FRCs (Reforpost) were etched with 37% H3PO4 for 1
      min and silanized (Porcelain Primer). Thereafter, they were cemented with the
      dual resin cement En-Force. The specimens were stored for 24 h, attached to an
      adapted device, and submitted to the pullout test in a universal testing machine
      (1 mm/min). The data were submitted to the one-way ANOVA and Tukey's test (alpha
      = 0.05). RESULTS: G1 (30.2 +/- 5.8 Kgf) displayed the highest pullout strength (p
      < 0.001) when compared to G2 (18.6 +/- 5.8 Kgf) and G3 (14.3 +/- 5.8 Kgf), which
      were statistically similar. Analysis of the specimens revealed that all failures
      occurred between the adhesive system and the root dentin (pullout of the post
      cement), regardless of group. CONCLUSION: The multiple-bottle, total-etch
      adhesive system provided higher pullout strength of the glass FRC when compared
      to the single-bottle, total-etch, and single-step self-etching adhesive systems.
      The null hypothesis was rejected (p < 0.001).

PMID- 16430016
TI  - Polyethylene fiber-reinforced composite inlay fixed partial dentures: two-year
      preliminary results.
AB  - PURPOSE: Polyethylene fiber-reinforced composite inlay fixed partial dentures
      (FPDs) have been under development for some time. There is a lack of data on the
      clinical performance of such prostheses. This prospective clinical study
      evaluated the clinical performance of polyethylene fiber-reinforced composite
      FPDs over two years. MATERIALS AND METHODS: Twenty-eight polyethylene fiber
      reinforced composite inlay FPDs were fabricated for 19 patients. The treatment
      plan included removal of the existing restorations, placement of an ultrahigh
      molecular weight polyethylene (UHMWP) fiber ribbon, and final restoration with a
      light-curing hybrid resin. The 28 polyethylene fiber-reinforced composite inlay
      FPDs were examined clinically after 2 years. RESULTS: All 28 FPDs were intact at
      the 2-year examination. There were no signs of fracture, debonding, or
      discoloration. CONCLUSION: Based on the results of this descriptive study, the
      polyethylene fiber-reinforced composite inlay FPDs were considered clinically
      successful at the 2-year examination.

PMID- 16430017
TI  - A four-year clinical evaluation of a highly filled hybrid resin composite in
      posterior cavities.
AB  - PURPOSE: To evaluate the four-year performance of a highly filled resin composite
      in Class II and Class I cavities. MATERIALS AND METHODS: Each of 63 participants
      received at least one pair of restorations of the same size: one resin composite
      (Tetric Ceram) and one calcium aluminate cement. Seventy-one pairs were placed.
      The restorations were evaluated clinically according to slightly modified USPHS
      criteria at baseline, after 6 months, 1, 2, 3, and 4 years. At 3 years, the
      calcium aluminate cement material showed an inacceptable clinical cumulative
      failure frequency of 57% and its evaluation was discontinued. RESULTS:
      Postoperative sensitivity was reported for 5 restorations (2 resin composite, 3
      calcium aluminate cement). At 4 years, a cumulative failure frequency of 7.5% was
      observed for the resin composite material. Reasons for failure were partial
      material fracture (2), cusp fracture (2) and endodontic treatment (1).
      CONCLUSION: An annual failure rate of 1.9% for the resin composite material
      provided a good clinical performance during the 4-year period, which fulfills the
      ADA criteria for posterior resin composite materials.

PMID- 16430018
TI  - An interview with Audrey Nelson. Interviewed by Steven Berman.

PMID- 16430019
TI  - A comprehensive grassroots model for statewide safety improvement.
AB  - BACKGROUND: The Maryland Patient Safety Center (MPSC) a collaboration of the
      Maryland Hospital Association and Delmarva Foundation for Medical Care, Inc., was
      designated by the State of Maryland in June 2004. A voluntary, nonregulatory
      initiative, the MPSC complements the state's regulatory efforts in mandatory
      reporting and support for performance improvement. PROGRAMS: The MPSC's mission
      is to bring health care providers together to understand causes of unsafe
      practices and to put practical, evidence-based improvements in place. Using a
      multifaceted approach, the MPSC implements its mission through education and
      training, safety culture collaboratives, adverse-event and near-miss reporting,
      research, and special projects. Participation in these initiatives is provided at
      no cost to Maryland providers. Early results show that health care leaders and
      front-line workers are embracing the MPSC's vision to make Maryland's health care
      the safest in the nation. More than 2,500 health care providers have participated
      in the MPSC's programs in its 15 months. Eighty percent of the state's hospitals
      are taking part in the intensive care unit (ICU) Safety Culture Collaborative,
      which has already yielded a 36% decrease in catheter-related blood stream
      infections and a 20% decrease in ventilator-associated pneumonia. A MODEL FOR
      OTHER STATES: The MPSC's approach can serve as a model for other states to
      emulate.

PMID- 16430020
TI  - Improving patient safety using interactive, evidence-based decision support
      tools.
AB  - BACKGROUND: Meridian Health developed interactive protocols using computerized
      physician order entry (CPOE), providing clinicians with a concurrent clinical
      decision-support tool that helps increase compliance with evidence-based
      guidelines. INTERACTIVE DECISION SUPPORT: Guidelines for acute myocardial
      infarction (AMI) were developed into interactive protocols that prompt the
      physician to administer aspirin and a beta-blocker at the time of admission to
      patients who present with suspected AMI but offer the opportunity to document
      contraindications instead. By March 2005 all three Meridian hospitals had
      implemented the AMI interactive protocol. Seventeen interactive clinical decision
      support protocols are now in use across six categories of care. RESULTS:
      Compliance rates for the AMI guidelines increased by 10% within two months of
      implementation and have been at 100% in all months when the interactive protocols
      have been used. Meridian is also seeing a steady climb in the number of total
      orders physicians are placing online, increasing as much as 46% at one hospital.
      DISCUSSION: Meridian physicians now recognize that CPOE is a valuable tool in
      improving patient safety through its interactive protocols. It has also enabled
      Meridian to analyze usage patterns as part of its continuous process improvement
      methodology. CONCLUSION: The use of interactive protocols using CPOE represents
      an innovative approach to improving patient safety.

PMID- 16430021
TI  - Building and sustaining a systemwide culture of safety.
AB  - BACKGROUND: In 2002, Sentara launched a systemwide initiative to significantly
      reduce events of harm to patients and employees. The initiative began at Sentara
      Norfolk General Hospital. Since then, the safety principles piloted there have
      been instituted throughout Sentara's integrated health care system of hospitals,
      nursing homes, and physician practices. ACCELERATING THE PACE OF IMPROVEMENT:
      Implementation at each local site begins with a thorough assessment of its safety
      culture. Four core areas of focus include (1) establishing safety as a core
      value, (2) creating Behavior-Based Expectations (BBEs) for error prevention that
      are tailored for staff, leaders, and physicians, (3) developing a state-of-the
      art root and common-cause analysis program, and (4) implementing an approach to
      focus and simplify work processes and procedure documentation. KEYS TO SUCCESS:
      Senior leadership demonstrated a commitment to making safety a core value by
      embedding safety into strategic priorities, incentives, rewards and recognition,
      and human resources policies and procedures; prioritization of operational goals
      to ensure the availability of time and resources to make the safety initiative
      the key focus; involvement of employees and medical staff each step of the way;
      establishment of site-based safety initiative teams of operational leaders with
      the responsibility for leading the safety initiative implementation and ensuring
      effective communication across the organization; and a willingness to learn and
      try successful techniques from high-reliability organizations outside health
      care.

PMID- 16430022
TI  - What do we know about financial returns on investments in patient safety? A
      literature review.
AB  - BACKGROUND: A framework was proposed for making a business case for patient
      safety interventions and to evaluate whether and how thoroughly financial aspects
      of investments and returns have been reported. METHODS: MEDLINE was searched from
      inception through January 21, 2005. Articles were selected if they reported on a
      patient safety intervention or a patient safety related outcome within the United
      States and indicated that a financial or economic analysis of the intervention
      was an objective. RESULTS: For 165 articles, a financial or economic analysis was
      indicated as an objective; 36.4% used original data, 28.5% used referenced data,
      and 35.2% provided no analysis. Only 13 articles (7.9%) included original data on
      start-up costs, 45 articles (27.3%) included original data on operating expenses
      and benefits, and 9 articles (5.5%) provided original financial data on outcomes.
      Of the 165 articles, 56.4% evaluated technological methods of improving patient
      safety, such as adoption of computer physician order entry, 20.6% evaluated
      changes in processes of care, such as staffing changes, and 23% involved other
      types of interventions or outcomes. DISCUSSION: Few articles provided complete
      information on the required investment and anticipated return on patient safety
      interventions. Use of standard financial techniques may strengthen the business
      case for patient safety interventions.

PMID- 16430023
TI  - Implementing research findings into practice using clinical opinion leaders:
      barriers and lessons learned.
AB  - BACKGROUND: An opinion leader-driven intervention to improve practice guideline
      based medication management for patients with schizophrenia was tested at four
      Department of Veterans Affairs health care facilities. The concept of using
      opinion leaders as disseminators of research evidence and internal agents of
      change has been widely reported. PROJECT OVERVIEW: Each intervention site
      received an intensive, multicomponent intervention during the course of one year.
      The project's process evaluation included ongoing brief surveys of physicians'
      attitudes and behaviors, logs of reports from opinion leader conference calls,
      and interviews with the opinion leaders toward the end of the implementation
      period. BARRIERS OR ISSUES AND POTENTIAL SOLUTIONS: Several barriers or
      problematic issues surfaced: (1) physicians do not always agree on who is an
      opinion leader; some sites may have no opinion leader; (2) some sites had poorly
      developed formal and informal social networks among physicians; (3) a focus on
      physicians only as agents of change; and (4) how much directive should be given
      to the opinion leaders concerning how to influence attitudes and behaviors?
      DISCUSSION: Four major problematic issues encountered during the project offer
      potential solutions for addressing them.

PMID- 16430024
TI  - Screen-saver technology: an easy way to enhance communication with employees.

PMID- 16430025
TI  - Synthesis and biological activity of picobenzide (3,5-dimethyl-N-(pyridin-4
      ylmethyl)benzamide) analogues as potential antipsychotic agents.
AB  - A series of analogues related to picobenzide (CAS 51832-87-2) have been prepared
      and have been used as starting material to obtain new trisubstituted oxazole
      derivatives. Two compounds showed a promising pharmacological profile in
      screening tests of antipsychotic activity, since they affected apomorphine
      induced hyperactivity without significant effects on stereotypies.

PMID- 16430026
TI  - Bioavailability investigation of two different oral formulations of citalopram, a
      so-called 'second generation' antidepressant drug.
AB  - Citalopram (CAS 59729-33-8) belongs to the so-called 'second generation'
      antidepressant drugs and is used for the treatment of patients with major
      depression or other depressive disorders. In the present study, two different
      oral citalopram formulations (Citalopram-ratiopharm film-coated tablets as test
      preparation and tablets of a reference preparation distributed in Germany) were
      investigated in 20 healthy volunteers in order to prove bioequivalence between
      both preparations. A single 40 mg oral dose was administered according to an
      open, randomised, two-period cross-over design in the fasted state. Blood samples
      for determination of citalopram plasma concentrations were collected at pre
      defined time points up to 168 h following drug administration. A wash-out period
      of 21 days separated both treatment periods. Citalopram plasma concentrations
      were determined by means of a validated HPLC method with fluorescence detection.
      Maximum plasma concentrations (Cmax), of 34.77 ng/ml (test) and 34.42 ng/ml
      (reference) were achieved. Areas under the plasma concentration-time curve (AUC0
      infinity) of 1,719.69 ng*h/ml (test) and 1,725.71 ng*h/ml (reference) were
      determined. The results showed nearly identical rate and extent of drug
      absorption. Also further pharmacokinetic parameters were well comparable with
      each other. Thus, tmax showed values of 3.29 h (test) and 3.77 h (reference). The
      plasma elimination half-life (t1/2) was 42.50 h (test) und 44.46 h (reference).
      Both primary target parameters Cmax and AUC0-infinity were tested parametrically
      by analysis of variance (ANOVA). Bioequivalence between test and reference
      preparation was demonstrated since for both parameters AUC and Cmax the 90 %
      confidence intervals of the T/R-ratios of logarithmically transformed data were
      in the generally accepted range of 80 %-125 %.

PMID- 16430027
TI  - Synthesis and pharmacological evaluation of novel quinoxalines as potential
      nonulcerogenic anti-inflammatory and analgesic agents.
AB  - Some new substituted quinoxaline and furo[2,3-b]quinoxaline derivatives have been
      synthesized and tested for their anti-inflammatory and analgesic activities and
      for their ulcerogenic potential. The pharmacological evaluation of selected
      synthesized compounds revealed that 5a was equipotent and compounds 3, 4b, 4e and
      5b possessed strong anti-inflammatory activity in chronic inflammatory models
      compared with indometacin (CAS 53-86-1) as reference drug. In addition, compound
      4a was the safest one and the others showed little ulcerogenic activity. All the
      tested compounds showed moderate analgesic activity compared to the reference
      drug.

PMID- 16430028
TI  - Effects of etodolac on P450 isoform-specific activities in human hepatic
      microsomes.
AB  - The effects of etodolac (CAS 41340-25-4) on P450 isoform-specific activities in
      human hepatic microsomes were examined. Etodolac had little effect on 7
      ethoxyresorufin O-deethylation (CYP1A2), coumarin hydroxylation (CYP2A6), 7
      benzyloxyresorufin O-debenzylation (CYP2B6), S-mephenytoin hydroxylation
      (CYP2C19), bufuralol hydroxylation (CYP2D6), chlorzoxazone hydroxylation (CYP2E1)
      and nifedipine oxidation (CYP3A4) at concentrations ranging from 10 to 50
      micromol/L. Etodolac inhibited tolbutamide hydroxylation (CYP2C9) with the Ki
      value of 64 micromol/L, suggesting that it is a weak inhibitor of CYP2C9. The in
      vivo drug interaction was predicted from the in vitro data using the [I]/([I] +
      Ki) value. Because the value was calculated to be almost 1, it is not likely that
      etodolac causes the drug interactions with the CYP2C9 substrates.

PMID- 16430029
TI  - Exploratory study on the effects of treatment with two mistletoe preparations on
      chronic hepatitis C.
AB  - Twenty-one patients with chronic hepatitis C were treated with a mistletoe
      preparation as monotherapy (either Iscador or Abnoba viscum) during one year. The
      treatment was well tolerated. Patients entering the study with elevated
      transaminases had a significant improvement, both for AST (aspartate
      aminotransferase) (p = 0.01) and for ALT (alanine aminotransferase) (p = 0.04).
      Quality of life significantly improved (p = 0.006) in patients with a low initial
      quality of life. Although one patient obtained a complete virological response,
      few effects on viral load were seen in the whole group. These results suggest an
      effect comparable to glycyrrhicin treatment: improvement of liver inflammation
      and thus possibly reduction of the long term complications, viz cirrhosis and
      liver cancer. Mistletoe preparations have the advantage of easy administration
      and low cost.

PMID- 16430031
TI  - Quantification of faropenem in human plasma by high-performance liquid
      chromatography.
AB  - A simple, sensitive and specific high-performance liquid chromatography (HPLC)
      method with ultraviolet detection (315 nm) was developed and validated for
      quantitation of faropenem (CAS 106560-14-9), the newest addition to the group of
      beta-lactam antimicrobials, in human plasma. Following solid-phase extraction
      using Waters Oasis SPE cartridges, the analyte and internal standard
      (hydrochlorothiazide, CAS 58-93-5) were separated using an isocratic mobile phase
      of 10 mmol/L acetate buffer (pH adjusted to 7.0 with dilute acetic acid) /
      methanol / triethyl amine (70/30/0.03, v/v/v) on reverse phase Waters symmetry
      C18 column. The lower limit of quantitation was 200 ng/mL, with a relative
      standard deviation of less than 2 %. A linear range of 200 to 25000 ng/mL was
      established. This HPLC method was validated with between-batch and within-batch
      precision of 1.6 to 2.3 % and 0.4 to 1.6 %, respectively. The between-batch and
      within-batch bias was -3.1 to 5.3 % and -6.0 to 1.5 %, respectively. Frequently
      coadministered drugs did not interfere with the described methodology. The
      stability of faropenem in plasma was excellent, with no evidence of degradation
      during sample processing (autosampler) and 30 days storage in a freezer. This
      validated method is sensitive, simple and repeatable enough to be used in
      pharmacokinetic studies.

PMID- 16430030
TI  - Synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile
      derivatives.
AB  - New series of 3-arylquinoxaline-carbonitrile derivatives have been synthesized
      from various 5-substituted or 5,6-disubstituted benzofuroxanes and tested for
      their in vitro and in vivo activity against the erythrocytic development of
      Plasmodium falciparum strain with different chloroquine-resistance status.
      Quinoxaline 1,4-dioxide derivatives showed superior antimalarial activity in
      respect to reduced quinoxaline analogues. The best activity was observed with
      nonsubstituted quinoxaline 1,4-dioxides in positions 6 and 7 of the aromatic ring
      and with a hydrogen or chloro substituent in para position of the phenyl group.

PMID- 16430032
TI  - [Nanotechnology, medicine, and minimally invasive surgery].

PMID- 16430033
TI  - [Evolution of the knowledge of urethral pathology in Valencia from the end of the
      XIX century to the middle of XX century. Historical documentary analysis].
AB  - OBJECTIVES: Urethral pathology has always been an interesting topic for study,
      being present in texts from 600 years B.C, where wood and metallic dilators are
      described. First external urethrotomies appear in the Jewish-Muslim period, and
      Francisco Diaz describes in 1588 the treatment of the prostate in his book
      "Tratamiento de las carnosidades de la verga". With Civiale and Maisoneuve,
      between 1700 and 1800, appears the description of the urethrotome, and finally in
      the middle XIX century starts the search for adequate tissues to replace urethra.
      METHODS: We review all articles on the topic of urethral pathology from authors
      from Valencia in that period, mainly published in the journal "Revista Valenciana
      de Ciencias Medicas". RESULTS: We emphasize the use of bulbs and sounds in the
      approach to urethral stenosis by several authors, with their advantages and
      limitations. We also emphasize the description of external urethrotomy by Prof.
      Molla. Finally, we point out the treatment of a posterior urethra fracture by
      tunneling reported by Dr. Alfredo Tramoyeres. CONCLUSIONS: Despite not being a
      topic with a high volume of publications, it has always interested authors. We
      describe all treatments, and sound insertion and dilation techniques as first
      option.

PMID- 16430034
TI  - [Evidence on the improvement of quality standards for retropubic surgery for
      BPH].
AB  - OBJECTIVES: To report the first consolidated results of the technical variation
      of the bladder-capsule plasty, a complement of the well-known trans-cervical
      hemostatic adenomectomy. METHODS: We analyze 65 recent consecutive patients with
      BPH undergoing surgery by such technique with follow-up between 6-48 months,
      analyzing the parameters which in this type of operation are significant to
      evaluate quality. RESULTS: We evaluated bleeding, transfusions, surgical wound
      complications, postoperative discomfort, number of days with catheter, and
      hospital stay; also reoperations and morbidity-mortality, which show a notable
      improvement in comparison with what appears to be typical of this operation,
      considered the most aggressive approach for the surgical treatment of BPH.
      CONCLUSIONS: We report a personal modification of the transcervical hemostatic
      adenomectomy, published in 1974, after an experience of more than 1000
      operations: the bladder-capsule plasty. The changes introduced in this 65 cases
      make us consider, even in present times, open surgery for BPH as the best
      solution for the obstructive problem in selected cases, with the lowest
      reoperation rates, and improving on factors such as "invasiveness" and "higher
      cost" which have been historically attributed to it.

PMID- 16430035
TI  - [Cholesterol embolism of the upper urinary tract as a clinical feature of
      atherosclerotic embolic vascular disease. Report of three cases, one of them
      simulating neoplasia].
AB  - OBJECTIVES: To report three cases of atherosclerotic embolic vascular disease
      with clinical presentation in the lower urinary tract. This disease is not
      frequent; it mainly affects the skin, kidneys and skeletal muscle. Other organs
      of the urinary tract are rarely affected and they are exceptionally the clinical
      site of debut without previous known involvement of other areas. METHODS/RESULTS:
      The first patient presented with hematuria associated with an
      ultrasound/cystoscopical image suspicion for neoplasia. Pathologic report of the
      transurethral resection chips showed polypoid cystitis with some small size
      arteries occupied by cholesterol needles, associated with inflammation, ulcers
      and hematic extravasation. The second patient underwent cystoprostatectomy for a
      transitional cell carcinoma and, incidentally, numerous cholesterol emboli were
      found, mainly in the lamina propria, but also in other layers of the bladder
      wall, prostate, urethra, veru montanum, and one seminal vesicle; this two latter
      sites have not being reported in previous publications. The third patient showed
      the embolus within a prostate biopsy core. CONCLUSIONS: This unfrequent disease
      may present as a bladder or prostatic process and be diagnosed by biopsy of these
      organs. It may simulate a bladder neoplasia on ultrasound or cystoscopy and
      should be included among related or etiologic entities of polypoid cystitis, a
      well-known simulator of neoplasia.

PMID- 16430036
TI  - [Cryotherapy III, Bibliographic review. Our experience (I)].
AB  - OBJECTIVES: To perform a bibliographic review of the main features of cryotherapy
      as a therapeutic option in the managemente of prostate cancer and to report our
      initial experience. METHODS: We employed the Endocare Fast-Trac system (Medipro)
      with 2,4 mm needles implanted in a single maneouvre without rack or transrectal
      US transducer support. Two cycles of freezing--hawing were employed, with apex
      backward movement when necessary. Freezing cycle duration was between 7-10
      minutes or more. The Onik maneouvre-injection of saline into the Denonvillier's
      space--diminishes the risk of rectal injury and fistula allowing reaching
      posterior limits of the ica-ball beyond the prostatic capsule. RESULTS: We
      treated 20 patients. Follow-up was between 30-36 months. 58% of the patients had
      unilateral prostate cancer, 42% bilateral. In accordance to the classic
      definition 9 patients were classified as low risk of extraprostatic disease, 6
      medium risk and 5 high risk; using number of positive cores as the criterion for
      risk 5, 6 and 9 were low, medium and high risk respectively. Per protocol
      prostate biopsies were performed in 18 patients 6, 12 and 24 months after
      treatment. Two patients underwent a second treatment due to persistence of cancer
      cells in the 6-month biopsy (11%). 3-month PSA nadirs after a total of 21 cryo
      treatments administered were < 0,2 ng/cc in 15 cases (78,9%), < 0,5 ng/cc in 17
      (89,4%) and < or = 1.0 ng/cc in 18 (94,7%); it was over 1 ng/cc in only 5,6%. 30
      month PSA for the same cutoff values was 27.8%, 50.0%, 66.6% and 33.3%,
      respectively. Prostate cancer cells were detected in the 12-month biopsies of
      5.5% cases. All 24-month biopsies were negative. COMPLICATIONS: We observed
      scrotal edema, hematoma, perineal pain and constipation which lasted 2-3 weeks. 1
      patient suffered injury of the mucosa at the prostatic urethra, which did not
      result in rectal fistula and was treated with bladder catheter for 3 months. 4
      patients had erectile dysfunction before treatment. All others presented erectile
      dysfunction after treatment; 3 of them (20%) recovered rigidity enough to have
      intercourse over the 30 month period. No urethral sloughing or acute urinary
      retention appeared and all patients are continent. CONCLUSIONS: Prostatic
      cryosurgery is an effective, minimally invasive procedure for the treatment of
      prostate cancer with very low surgical risk, low morbidity and almost null
      mortality.

PMID- 16430037
TI  - [Epidemiological analysis of the squamous cell carcinoma of the penis in a 90,000
      inhabitant health area].
AB  - OBJECTIVES: To establish the most relevant epidemiological features of the
      squamous cell carcinoma of the penis (absolute, adjusted and accumulated
      incidence, incidence density, and epidemic index), as well as its related
      survival. METHODS: We included all patients with the diagnosis of squamous cell
      carcinoma of the penis in the health area No. VIII of Ciudad Real (90,000
      inhabitant) between January 1981 and December 2003. Data from the national
      Institute of Statistics were used for population adjustments. A Cox regression
      model was applied for survival analysis. RESULTS: The incidence of squamous cell
      carcinoma of the penis has increased over the last years (yearly increase 5.86%)
      with a high mortality rate within the first year (median survival 407 days)
      CONCLUSIONS: It would be recommendable to intensify preventive measures to try a
      stop the increase in incidence, as well as successful adjuvant treatments to
      increase cancer specific survival.

PMID- 16430038
TI  - [The role of prostate volume in ultrasound guided transrectal prostate biopsy: is
      it as important as a marker as PSA?].
AB  - OBJECTIVES: The limitations of PSA to identify patients with prostate cancer
      prompted the definition of different parameters trying to increase specificity
      without reducing sensitivity. This paper studies the relationship of volume and
      presence of prostate cancer in sextant biopsies. METHODS: We collected the
      results of prostate biopsies performed to 6000 patients between 1994 and 2002.
      861 of them underwent more than one biopsy, adding up for a total of 7127
      biopsies. Various predictive models to identify factors related to positive
      biopsy were constructed. RESULTS: Mean prostate volume is 14.6 +/- 66.2 cc for
      the first biopsy, increasing in successive biopsies to 85.17 cc. A high incidence
      of prostate cancer was observed in small prostates, reaching 67.2% of those with
      normal size (< 20 cc) and diminishing with the increase of volume down to only
      19.7% in those larger than 50 cc (p < 0.0001). In second biopsies of patients
      with PSA between 4 and 10 ng/ml and gland volume higher than 50 cc percentage of
      biopsies positive for cancer was below 10%. Multivariant logistic regression
      showed that PSA, volume and PSA density were related with positive biopsies, but
      not free/total PSA ratio. CONCLUSIONS: Standard PSA cutoffs are not adequate for
      a proper diagnosis of prostate cancer by ultrasound guided transrectal biopsy
      Volume (BPH) has a significant influence in PSA values and results of the biopsy,
      so that it should be taken into consideration when indicating biopsies.

PMID- 16430040
TI  - [Penile prosthesis. Quality outcomes and morbidity].
AB  - OBJECTIVES: To study patient satisfaction and complications appeared in a series
      of patients with erectile dysfunction undergoing implant of penile prosthesis.
      METHODS: Retrospective study of all patients undergoing surgical treatment for
      erectile dysfunction by penile prosthesis implant between 1993 and 2003.
      Collected data included patient age at the time of surgery, previous treatment,
      and significant medical history. We reviewed the models of prosthesis employed,
      incisions, and complications appeared. Finally, a questionnaire was elaborated to
      establish the level of patient satisfaction. RESULTS: 24 prostheses were
      implanted between 1993 and 2003. Mean patient age was 56.6 +/- 7.56 years (36
      63), median 59.5 yr. Penile-scrotal incision was employed in 13 (54.16%)
      patients, suprapubic incision in 6 (25%) and subcoronal incision in 1 (4.16%).
      Type of prosthesis: semirrigid AMS 600 9 (37.5%), semirrigid AMS 650 10 (41.66%);
      the two component hydraulic prosthesis AMS Ambicor was used only in one case. Six
      (25%) patients presented complications. 16.66% were minor, cavernositis, pain,
      hematoma or prosthesis extrusion. Prosthesis extraction was necessary in 2
      (8.33%) cases. 13 (54.16%) patients responded to the telephone survey 85% of them
      use their prosthesis. 54% percent refer adequate self-satisfaction and partner
      satisfaction (well satisfied/much satisfaction). 23% not too bad, and the
      remainder 23% bad or very bad. CONCLUSIONS: Despite the highest rate of
      postoperative complications, penile prosthesis is adequately accepted by patients
      with erectile dysfunction, even malleable models. Patient satisfaction is high,
      being higher in partners. Most patients would desire to undergo surgery again if
      they were in the same situation.

PMID- 16430039
TI  - [Outpatient surgical treatment of female stress urinary incontinence].
AB  - OBJECTIVES: To evaluate the results of the outpatient surgical treatment of
      genuine female stress urinary incontinence (SUI) over a five year period since
      the integration of the Department of Urology in the Ambulatory Surgery Unit at
      our hospital "Consorcio Hospital General Universitario de Valencia" (CHGUV).
      METHODS: Between January 2000 and December 2004 26 patients (ages 49-78; mean age
      69.8 yr) with the diagnosis of SUI underwent tension-free suburethral mesh sling
      (TVT) outpatient operations under local anesthesia-sedation at the ambulatory
      surgery unit of the CHGUV. All patients had clinical and urodynamic evaluation,
      excluding those presenting genital prolapse or non compliance with the social
      requirements for ambulatory surgery. Previous anti-incontinence surgery was not
      an exclusion criterion. We evaluate inclusion and discharge criteria, results and
      satisfaction degree measured by a questionnaire. RESULTS: 22 patients (85%) had
      genuine SUI and 4 (15%) had mixed UI with predominance of the stress component.
      54% (14) of the patients were ASA I, 31% (8) ASA II, and 15% (4) well compensated
      ASA III. Operation tolerance under local anesthesia (20-30 ml 1% lidocaine) was
      good in all patients, having used additional sedation-analgesia (propofol
      remifentanil IV perfusion) in 10 of them (38%). Mean operative time was 30
      minutes (25-45) and stay at the unit discharge was 100 min. (80-140). All
      patients were discharged the same day. None of them required readmission or
      presented urinary retention after catheter removal. SUI disappeared in all of
      them. Three patients presented postoperative urge incontinence responsive to oral
      anticolinergic drugs. Our results are similar to those obtained with epidural
      anesthesia and hospital admission, being the degree of satisfaction with
      treatment higher than 95%. CONCLUSIONS: The development of new, revolutionary
      systems for the treatment of SUI has simplified the surgical treatment of this
      entity, so that we can say a high percentage of patients may be included in an
      ambulatory surgery program, significantly improving cost-efficacy without
      diminishment of health-care quality or patient satisfaction.

PMID- 16430041
TI  - [Peyronie's disease. Evaluation of 3 therapeutic modalities: propoleum, laser and
      simultaneous propoleum-laser].
AB  - OBJECTIVES: To compare the results of treatment of peyronie's disease with
      propoleum, laser, and simultaneous propoleum-laser. METHODS: Prospective
      research. Twenty-eight patients with Peyronie's disease from the hospitals Freyre
      de Andrade,Fajardo, Clinico Quirurgico y Habana Campo were studied between May
      2002 and August 2003. They were divided into three groups: 1) treatment with
      propoleum: 10 patients; 2) treatment with laser: 8 patients; and 3) treatment
      with propoleum + laser: 10 patients. A registered formula of Propoleum powder was
      employed in daily 900 mg capsules over six months. 30 sessions of laser were
      applied to the plaque divided in periods of 10 sessions every 2 months. STUDY
      VARIABLES: age, race, date of disease start/clinical improvement correlation,
      beginning of improvement after treatment. Data were processed in a statistical
      software (Epinfo-6) and multivariate analysis with non parametric methods was
      employed. RESULTS: Mean age was between 4th and 7th decade in all groups.
      Caucasian race was predominant. The propoleum-laser group achieved the greater
      diminishment of the plaque among those with one or two years of disease
      evolution. Pain was not the main symptom in these patients. The greater
      diminishment of the curvature was obtained in the propoleum groups, with a mean
      diminishmeet of 10.8 (propoleum only) and 10.3 (Propoleum+ laser) in comparison
      to the laser group with a mean decrease of 8 and mean increase of 12.6. Mean
      plaque diminishment measured clinically was 2.3 cm and 1.5 cm in the propoleum
      groups, respectively, and 1.2 cm in the laser group. Ultrasound measurement mean
      diminishment was 2.3 mm and 12.16 mm in the propoleum groups. The laser results
      were not comparable due to the low number of patients in relation to the other
      groups. CONCLUSIONS: 1-best results appeared in the groups treated with propoleum
      in patients with 1-2 years of disease. 2-Diminishment of the curvature angle,
      physical or ultrasound measurement of the plaques was greater in the propoleum
      groups. 3-After the start of treatment, the propoleum-laser group referred early
      improvements, and the propoleum group referred continuous progressive
      improvement; only a few patients in the laser group referred improvement. 4
      Treatment with propoleum was more effective and laser increased its action, being
      propoleum in monotherapy less complex in its application and with a better cost
      benefit ratio.

PMID- 16430042
TI  - [Extra peritoneal laparoscopic radical prostatectomy. Preliminary results].
AB  - OBJECTIVES: Presentation of our initial experience with the practice of the
      laparoscopic radical prostatectomy through the extraperitoneal access (ELRP). We
      describe the proceeding and its technical difficulties, time consumption and
      complications. METHODS: From January to May 2005 we have indicated 17 ELRP in our
      institution. Two of them were performed with the help of a mentor. We followed
      the Brussels technique but without preservation of the neuro vascular bundles.
      RESULTS: Laparoscopic approach was indicated in 17 patients, 8 of them were
      completed and 9 converted to open surgery. Of the cases performed without
      external aid (which are the analysed in this communication), 6 were pure
      laparoscopic and 9 were permuted to open. Of the last 6, only one was not
      completed by laparoscopy. Mean operative time was 304 minutes (355 for the pure
      laparoscopy cases). Transfusion rate was 13%. Positive surgical margins were
      observed in 26% of the cases (16% of the complete laparoscopic procedures). There
      were not major complications. Not ileus was observed. In one case, bladder
      catheter had to be replaced after 7 days because it was not properly placed
      during surgery. Conversion to open surgery during extraperitoneal laparoscopic
      proceeding is not very difficult but previous surgical experience is required.
      CONCLUSIONS: ELPR is feasible in an institution like ours but is necessary a team
      with previous experience in laparoscopic surgery and the aim of invest a big
      effort, specially regarding operative time. Initial learning curve has not caused
      any important complication.

PMID- 16430043
TI  - [Prostatic stromal sarcoma in a 20-year-old patient].
AB  - OBJECTIVE: Prostatic tumors are the most frequent malignant neoplasms in men,
      most of them being constituted by carcinomas; only 0.2% of malignant prostatic
      neoplasms are of mesenchimal origin. They are not well known, especially those of
      prostatic stromal phenotype. METHODS AND RESULTS: We report the case of a 20 year
      old man with a prostatic stromal sarcoma. After total cystoprostatectomy a tumor
      measuring 8 cm could be seen, replacing almost the whole prostate.
      Microscopically a spindle cell neoplasia with moderate atypia and a high mitotic
      index entrapping few elongated prostatic ducts (adopting a phyllodes tumor
      morphology) was observed. CONCLUSION: The clinical behavior of these infrequent
      sarcomas is not well-established. Recurrences are not uncommon whereas lung and
      bone metastases have been described. Twelve months after surgery our patient is
      alive without evidence of disease.

PMID- 16430044
TI  - [Bladder leiomyoma. A case report and literature review].
AB  - OBJECTIVES: To report a new case of bladder leiomyoma. METHODS: A 20 mm tumor of
      the right lateral wall of the bladder was incidentally found in a pelvic
      ultrasound study of a 29-year-old female. The cystogram showed the presence of a
      filling defect in the same side. Cystoscopy showed a right lateral wall tumor
      with normal mucosal cover. RESULTS: With the working diagnosis of bladder
      leiomyoma, transurethral resection of the bladder tumor was performed, and
      pathology confirmed the diagnosis. Postoperatively, the patient developed a
      calcareous plaque on the resection area which was treated by transurethral
      resection of the plaque and leiomyoma remainders and subsequence urine
      acidification. CONCLUSION: Although it is a rare tumor, in certain circumstances
      it is possible to establish the working preoperative diagnosis with a high index
      of suspicion. On the other hand, due to the benign character of the process,
      conservative surgery (transurethral resection in this case) offers excellent
      results.

PMID- 16430045
TI  - [Bladder leiomyoma in a 17-year-old male patient].
AB  - OBJECTIVES: Bladder leiomyoma is a rare tumor, its frequency being estimated
      below 1%. METHODS: We report the case of a 17-year-old mole patient presenting
      with hematuria and lower urinary tract irritative symptoms whose work up
      discovered two small bladder tumors. RESULTS: After TUR of the lesions the
      diagnosis of bladder leiomyoma was established; no recurrences have appeared on
      follow-up. CONCLUSIONS: Bladder leiomyoma is a benign tumor, therefore surgery
      should be the most conservative. Bibliographic review of the Spanish urologic
      journals shows that this is the youngest patient reported to date.

PMID- 16430046
TI  - [Spermatic cord rhabdomyosarcoma in an adult].
AB  - OBJECTIVES: To report one case of spermatic cord rabdomyosarcoma in an adult
      patient. METHODS: We report the case of a 36-year-old male presenting with a
      painful left inguinal scrotal mass. RESULTS: Left radical orchiectomy was
      performed with excision of the mass. Pathology showed a spermatic cord
      rabdomyosarcoma. The patient received several cycles of systemic chemotherapy.
      CONCLUSIONS: Spermatic cord rabdomyosarcoma is a rare tumor derived from the
      undifferentiated mesoderm. It rarely appears after the second decade of life.
      Local-regional recurrence after surgery is very frequent. There are adjuvant
      treatments, the indication and use of which couldn't be included in proper
      protocols due to the low incidence of this tumour in adults.

PMID- 16430048
TI  - [Ultrasound diagnosis of intratesticular varicocele].
AB  - OBJECTIVES: Varicocele is a relatively frequent entity; in most cases venous
      dilation only involves the extratesticular portion, but 2% of the cases present
      intratesticular dilation. We report one case of left intratesticular varicocele.
      METHODS/RESULTS: We report the case of a 25-year-old male patient referred for
      study of left testicular pain, whose work up only found left intratesticular
      varicocele. CONCLUSIONS: Intratesticular varicocele is an infrequent entity which
      can be associated with testicular pain, scrotal mass and infertility or may be
      asymptomatic. The diagnosis is established by Doppler ultrasound; if symptomatic,
      it may be treated by spermatic vein ligation.

PMID- 16430047
TI  - [Cavernous haemangioma as the cause of ureteral pyelic junction obstruction].
AB  - OBJECTIVES: To report one case of cavernous haemangioma in the upper urinary
      tract. METHODS/RESULTS: 29-year-old female presenting with right renal colic
      whose IVP showed UPJ obstruction. Dismembered pyeloplasty was performed and
      pathology reported a cavernous haemangioma as the cause of stenosis. CONCLUSIONS:
      Cavernous haemangioma, a rare upper urinary tract pathology, should be considered
      in the differential diagnosis of causes of UPJ obstruction.

PMID- 16430050
TI  - The "Krukrnberg" tumor in male.
AB  - OBJECTIVES: The ovarian metastasis by a gastrointestinal cancer is called
      Krukenberg tumor. We report a case of metastasis to the testis and epididymis by
      gastric cancer that can be the analogue in male. METHODS: A patient, submitted to
      total gastrectomy for a poorly differentiated gastric adenocarcinoma (TNM stage:
      pT3 GIII N+ M 1) developed one year later a painful swelling of the right
      hemiscrotum and groin. The palpation revealed a painful mandarine-like mass
      conglobated in the right testis and epididymis, with a further mass at the
      external inguinal-ring and multiple little nodes along the spermatic cord. An
      inguinal orchifuniculectomy was performed and the histological tests described a
      poorly differentiated, microtubular adenocarcinoma, infiltrating the connective
      tissue, without spreading to the testis, that was properly structured. The
      atypical tumor formations expressed carcinoembryonal antigen, but were negative
      for -HCG and PSA. The immune-histochemical results confirmed the diagnosis of an
      adenocarcinoma. RESULTS/CONCLUSION: The metastasis in testicles and/or epididymus
      are rare and cannot be differentiated clinically or by imaging procedures from a
      primary testicle neoplasia. Only the exact anamnesis of previous tumors and the
      age can provide some indications. The therapy of choice is however represented by
      inguinal orchifuniculectomy.

PMID- 16430051
TI  - [Decayed, filled and missing teeth as a forensic-odontologic aid for determining
      the age above 18 years: A radiographic study of orthopantomograms from a group of
      teenagers and young adults].
AB  - The human teeth are a valuable source of information concerning identification
      and age calculation in forensic sciences. Dental treatment often causes permanent
      alteration of the teeth, which is visible on radiographs. The correlation of
      decayed, missing or filled teeth and chronological age has not yet been used for
      determining the accomplished 18th year of life in teenagers and young adults, e.
      g. for legal and anthropological purposes. The aim of this study was to determine
      whether the evaluation of these findings on radiographs correlates with the
      chronological age in teenagers and young adults. MATERIAL AND METHODS: The dental
      X-rays (orthopantomograms, OPG) of 1053 outpatients (age: 14 to 24 years) were
      evaluated. The values "decayed", "missing", or "filled" were recorded for each
      tooth present. The data were then calculated using statistical tools. RESULTS:
      The correlation between the number of missing teeth and the chronological age is
      low. However, the positive predictive value of determining the age of 18 years
      for certain types of teeth proved to be very high, even up to 100 %. Further,
      high numbers of filled teeth gave reasonable positive predictive values for an
      age of 18 years. The number of decayed teeth did not correlate with age.
      DISCUSSION: This study provides for the first time predictive values for the
      estimation whether a person is 18 years of age, based on the evaluation of
      decayed, missing or filled teeth on OPGs only. Whereas the number of patients
      with such findings is generally low in this age group, some of the positive
      findings can be used for age estimation as an adjunct to other sources of age
      calculation. The sole application of these items is not recommended, as sanitary
      conditions of the teeth depend on both social and individual circumstances.
      Therefore, the calculated values also reflect the culture of the sample studied.
      Finally, they are time-dependent and have to be compared to data from other
      populations. These results have some bearing on the field of forensic odontology.

PMID- 16430052
TI  - [Suicide with multiple graze shots].
AB  - A 77-year-old man was found in his flat with a shot to the right temple. In spite
      of hospital treatment he died from the head injury the next day. The weapon at
      the scene used for committing the suicide was a pistol, make Kaba Special
      (calibre 6.35 mm). At autopsy, the right temporal region showed a surgically
      treated, originally stellate gunshot entrance wound with a powder cavity. Close
      to this penetrating gunshot wound there were 3 parallel graze shot injuries of
      the scalp. The autopsy findings were consistent with the assumption that all the
      shots had been fired by the victim himself with suicidal intent. The injury
      pattern is presented and discussed in relation to the results of the technical
      investigation of the weapon and the findings at the scene.

PMID- 16430053
TI  - [The case of a corpse found in a fox's den--forensic and criminological aspects].
AB  - Whenever foul play is suspected in a death, the forensic pathologist is required
      to examine the corpse where it is found. In the case described here, the unusual
      location of the corpse initially led investigators to suspect a crime was
      involved. A thorough examination of the site and the autopsy results ultimately
      pointed to a not-violent manner of death, although the advanced state of
      decomposition made it impossible to determine the exact cause of death. The fact
      that the victim crawled into a fox's den to die can be interpreted as a primitive
      reaction in a case of death due to hypothermia. Criminological aspects of the
      case are also discussed.

PMID- 16430054
TI  - [Prosthetic restorations, dental root fillings and periodontal bone resorptions
      as a forensic-odontologic aid for determining the age above 18 years: A
      radiographic study of orthopantomograms from a group of teenagers and yount
      adults].
AB  - The human teeth are a valuable source of information concerning identification
      and age calculation in forensic sciences. Dental treatment often causes permanent
      alteration of the teeth, which is visible on radiographs. The correlation of
      prosthetic restorations, root canal fillings and periodontal bone loss with
      chronological age has not yet been used for determining the completed 18th year
      of life in teenagers and young adults, e. g. for legal and anthropological
      purposes. The aim of this study was to determine whether the evaluation of such
      findings on radiographs correlates with the chronological age in teenagers and
      young adults. MATERIAL AND METHODS: The dental X-rays (orthopantomogram, OPG) of
      1053 outpatients (age: 14 to 24 years) were avaluated. The values "prosthetically
      restored", "filled dental root", or "periodontal bone loss" were recorded for
      each tooth present. The data were then evaluated using statistical tools.
      RESULTS: The correlation between the number of prosthetically restored teeth and
      the chronological age is high. The positive predictive value of determining an
      age of at least 18 years proved to be very high. However, these findings are
      rarely present in this age group. The number of endodontically treated teeth
      correlated less exactly with age. On the other hand, the determination of
      periodontal bone loss gave reasonable positive predictive values for the
      threshold value "chronological age of 18 years or more". DISCUSSION: This study
      provides for the first time predictive values for the estimation whether a person
      is 18 years of age, based on the evaluation of teeth with prosthetic
      restorations, root canal fillings or periodontal bone loss on OPGs only. Whereas
      the number of patients with such findings is generally low in this age group,
      some of the positive findings can be used for age estimation as an adjunct to
      other sources of age calculation. The sole application of these criteria is not
      recommended, as sanitary conditions of the teeth depend on both social and
      individual circumstances. Therefore, the calculated values also reflect the
      culture of the sample studied. Finally, they are time-dependent and have to be
      compared to data from other populations. These results have some bearing on the
      field of forensic odontology.

PMID- 16430055
TI  - Tumor escape from the immune response: a major hurdle for successful
      immunotherapy of cancer?

PMID- 16430056
TI  - Epidemiological aspects in Western countries.

PMID- 16430057
TI  - Urology and gynaecology cancer epidemiology in Tunisia.

PMID- 16430058
TI  - Descriptive statistics of urogenital cancer in Egypt and Asian area.

PMID- 16430059
TI  - Cancer incidence in Eastern Libya: preliminary result of the year 2003.

PMID- 16430060
TI  - Genetics of uro-genital cancer: prostate and ovary.

PMID- 16430061
TI  - Histological prognosis of uro-gynecological cancers.

PMID- 16430062
TI  - Staging of the urinary bladder tumors.

PMID- 16430063
TI  - MRI in uro and gynaecological cancer.

PMID- 16430064
TI  - Tumor markers in urogynaecological tumors.

PMID- 16430065
TI  - Radiotherapy in endometrial cancer.

PMID- 16430066
TI  - Chemotherapy for endometrial carcinoma.

PMID- 16430067
TI  - [History of Arabic medicine].

PMID- 16430068
TI  - Conservative surgery in cervical cancer.

PMID- 16430069
TI  - Cervical cancer and HPV.

PMID- 16430070
TI  - Chemotherapy in cervical cancer.

PMID- 16430071
TI  - Penile carcinoma: strategy of treatment.

PMID- 16430072
TI  - Advanced prostate cancer. Hormonal treatment.

PMID- 16430073
TI  - Current strategies in the treatment of metastatic hormone-refractory prostate
      cancer.

PMID- 16430074
TI  - What news in urological cancer.

PMID- 16430075
TI  - Surgery for testicular cancer: indication, results and technical aspects.
AB  - The standard therapeutique approach to patients with advanced germ cell tumors of
      the testis is a combination of systemic chemotherapy with surgical removal of the
      residual disease. The indication of surgery, residual tumor resection (RTR) or
      retroperitoneal lymph node dissection (RPLND), has changed during the last 10
      years. Sugery is not longer recommended after chemotherapy of pure seminoma and
      surveillance of the residual tumor is the favored option. RPLND is a critical
      component of the treatment armentarium in low-stage nonseminomatous germ cell.
      RPLND is an accurate staging tool prviding important information to dtermine the
      need for chemotherapy. When performed properly, RPLND eliminates the
      retroperitoneum as a site for relapse, wich in turn provides emotional and
      psychological relief to the patient, and simplifies the follow-up protocol. In
      advanced nonseminomatous tumours, surgery after chemotherapy is recommended in
      most of the cases since large studies have shown that a considerable proportion
      of patients with complete radiological remission after chemotherapy harbor vital
      carcinoma or teratoma. Prediction models of necrosis after chemotherapy in order
      to avoid RTR are generally accepted since the accuracy of most models is too low.
      RTR is indicated in patients with elevated markers after two different
      chemotherapy regimens (including salvage chemotherapy) either to resect teratoma
      or cystic residual disease or to remove chemorefractory disease. Laparoscopic
      approache is a viable staging tool; however, oncologic control of the
      retroperitoneum has not been reliably determined.

PMID- 16430076
TI  - High dose chemotherapy in germ cell tumors.

PMID- 16430077
TI  - Contemporary management of stage T1 transitional cell carcinoma of the bladder.

PMID- 16430078
TI  - Adjuvant radiation therapy for muscle-invasive bladder cancer.

PMID- 16430079
TI  - Transforming the health system from the inside out.
AB  - The movement toward electronic medical records gains speed with daily reports of
      another insurer offering enrollees online records, millions of dollars spent on a
      new electronic system, or new standards for health information technology. As
      welcome as these developments are, they represent merely stepping stones that are
      leading to a far more profound and lasting transformation of our health system.
      Ultimately, an information-enabled system will emerge that is very different from
      today's document-bound, fragmented delivery system. We are rapidly approaching an
      era where the size of a health system will be gauged not by the number of
      buildings on its campus but by its ability to move petabytes of data to the right
      people at the right time.

PMID- 16430080
TI  - Connecting the providers in your healthcare community: one step at a time.
AB  - The practice of medicine is a business of communications. Communications can be
      facilitated by technology. Healthcare providers organized in medical practices,
      hospitals, and nursing homes have tremendous needs to effectively communicate
      within their organizations and between their organizations. The focus on
      electronic medical records comes not only from the need to communicate but also
      from a desire to reduce administrative costs and to improve services and quality
      of care to patients. Frustration with the inadequacies of a paper chart-filing
      system drives providers in all delivery venues toward technology at an increasing
      rate. Implementation barriers to technology adoption in medical practices can be
      overcome by incremental approaches and knowledge-transfer assistance from
      affiliated community healthcare partners such as hospitals.

PMID- 16430081
TI  - Making progress in health information technology: more realistic leadership, less
      hype.

PMID- 16430082
TI  - The EHR paradox.

PMID- 16430083
TI  - Achieving the vision of EHR--take the long view.

PMID- 16430084
TI  - Effect of C-terminal 44 amino acids deletion on activity of Haemophilus
      influenzae UvrA protein.
AB  - UV-sensitive mutant strain of Haemophilus influenzae Rd MBH3, is 20 times more
      sensitive to UV irradiation than the wild type strain. The mutation responsible
      for increased UV sensitivity of the strain was identified as G --> A transition
      predicting synthesis of truncated UvrAdeltaC44 protein (Balsara & Joshi).
      Recombinant UvrAdeltaC44 protein was purified for the first time under denaturing
      conditions. The molecular weight of the recombinant protein was estimated as
      approximately100 kDa. Recombinant UvrAdeltaC44 protein was found to be less
      efficient in its ATPase and DNA binding activity as compared to the wild type
      protein. Recombinant plasmid carrying uvrAdeltaC44 gene could partially
      complement the UvrA deficiency in E. coli UvrA mutant.

PMID- 16430085
TI  - Studies on diagnostic potential of secretory antigens of Mycobacterium bovis.
AB  - Culture filtrate proteins (CFPs) of M. bovis were produced by culturing the
      organism for a period of 3 weeks. These CFPs elicited a good delayed
      hypersensitivity (DTH) reaction in cattle and guinea pig. However, CFPs showed
      least cross-reactivity when tested in guinea pigs sensitized with M. bovis BCG
      and M. phlei. CFPs were found to be well recognized by T-cells of single
      intradermal test (SIDT) positive cattle and were also sero-reactive. Lymphocyte
      transformation assay revealed the culture filtrate antigens as major T-cell
      antigens. CFPs induced a good interferon gamma release as compared to
      conventional antigen, PPD, thereby highlighting their diagnostic capabilities.

PMID- 16430086
TI  - Hypothyroid state reduces calcium channel function in 18-day pregnant rat uterus.
AB  - Hypothyroidism significantly reduced the mean amplitude and increased the mean
      frequency of spontaneous rhythmic contractions in 18 day pregnant rat uterus.
      Nifedipine (10(-12)-10(-9) M) and diltiazem (10(-10)-10(-6) M) caused
      concentration related inhibition of the myogenic responses of the uterine strips
      obtained from both pregnant and hypothyroid state. However, nifedipine was less
      potent (IC50:2.11 x 10(-11) M) in pregnant hypothyroid state as compared to
      pregnant control (IC50: 3.1 x 10(-12) M). Similarly, diltiazem was less potent
      (IC50: 3.72 x 10(-9) M) in inhibiting the uterine spontaneous contractions in
      hypothyroid than in pregnant rat uterus (IC50:5.37 x 10(-10) M). A similar
      decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100
      mM)-induced tonic contraction and K(+)-stimulated 45Ca2+ influx was observed with
      these calcium channel antagonists in uterus obtained from hypothyroid pregnant
      rats compared to the controls. Nifedipine-sensitive influx of 45Ca(2+)-stimulated
      either by K+ (100 mM) or by Bay K8644 (1,4-dihydro-2,6-methyl-5-nitro-4-[2'
      (trifluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10(-9) M) was
      significantly less in uterine strips from hypothyroid rats compared to controls.
      The results suggest that the inhibition of uterine rhythmic contractions may be
      attributable to a reduction in rat myometrial Ca2+ channel function in the
      hypothyroid state.

PMID- 16430087
TI  - Progesterone restores stress induced inhibition of estrous behavior in rat.
AB  - Exposure to a stressor (mild electrical shocks to foot, five times per episode,
      at 1800, 1830, 1900 and 1930 hrs of proestrus) coinciding with period of pre
      ovulatory progesterone secretion in rats abolished estrous behavior as shown by
      the absence of lordosis response and a significant increase in rejection quotient
      compared to controls. These rats did not show spermatozoa in the vaginal smear
      next day morning in contrast to their presence in controls. On the other hand,
      rats treated with progesterone (a single injection, 500 microg in 0.1 ml olive
      oil at 1800 hr of proestrus) prior to exposure to stressor showed normal estrous
      behavior, as shown by significantly lower rejection quotient than rats exposed to
      stress alone, lordosis quotient similar to controls and presence of spermatozoa
      in the vaginal smear next day. The results, albeit indirectly, to the best of our
      knowledge, first time indicate that stress induced impaired steroidogenesis leads
      to suppression of estrous behavior.

PMID- 16430088
TI  - Modulatory effect of dietary factors on iron-induced in vivo lipid peroxidation
      in liver and serum of albino rats.
AB  - Effect of a computed diet based on cereals and spices incorporated with either
      crude palm oil (CPO)/soybean oil (SBO)/cod liver oil (CLO) at 10% level in the
      diet in modulating iron-induced in vivo lipid peroxidation was carried out during
      a 12 week study in albino rats. Three groups of rats, each divided into three
      sets were fed diets based on casein/ragi/jowar incorporated with CPO or SBO or
      CLO. The casein group of rats did not receive any spice mixture, while the ragi
      and jowar groups received spice mixture at 2.5% level. Serum lipid analysis
      showed significant increase in cholesterol, LDL-c + VLDL-c and decrease in HDL-c
      levels in all the iron treated group of animals. In liver, non-significant
      increase in total cholesterol triglyceride and decrease in phospholipid levels
      were noted. Fatty acid profile of liver tissue exhibited low 18:2 levels in
      various experimental groups due to peroxidation of membrane lipids.
      Histopathological examination of liver tissue in particular showed mild
      cytoplasmic vacuolation in control group of rats fed ragi/jowar and moderate
      vacuolation in all the iron-treated groups. The results demonstrate that
      different dietary components can beneficially modulate free radical mediated
      oxidative stress induced by lipid peroxidation.

PMID- 16430089
TI  - In vitro antioxidant activity of Diospyros malabarica Kostel bark.
AB  - Antioxidant activity of defatted methanol extract of D. malabarica bark was
      studied for its free radical scavenging property on different in vitro models
      e.g. 1,1-diphenyl-2-picryl hydrazyl (DPPH), nitric oxide, superoxide, hydroxyl
      radical and lipid peroxide radical model. The extract showed good dose-dependent
      free radical scavenging property in all the models except in hydroxyl radical
      inhibition assay. IC50 values were found to be 9.16, 13.21, 25.27 and 17.33
      microg/ml respectively in DPPH, nitric oxide, superoxide and lipid peroxidation
      inhibition assays. In hydroxyl radical inhibition assay 1000 microg/ml extract
      showed only 10% inhibition with respect to the control. Measurement of total
      phenolic compounds by Folin-Ciocalteu's phenol reagent indicated that 1 mg of the
      extract contained 120.7 microg equivalent of pyrocatechol. The results indicate
      that the antioxidant property of the extract may be due to the high content of
      phenolic compounds. However, the underlying mechanism may not involve hydroxyl
      radical scavenging property.

PMID- 16430090
TI  - Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in
      mice.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by the
      selective loss of dopamine (DA) neurons of the substantia nigra pars compacta
      (SNc). The events, which trigger and/or mediate the loss of nigral DA neurons,
      however, remain unclear. Neuroleptic-induced catalepsy has long been used as an
      animal model for screening drugs for Parkinsonism. Administration of haloperidol
      (1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in mice.
      BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50 and
      100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced
      catalepsy. The results indicate that BR-16A or ashwagandha has protective effect
      against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A
      could be used in preventing the drug-induced extrapyramidal side effects and may
      offer a new therapeutic approach to the treatment of Parkinson's disease.

PMID- 16430091
TI  - Effect of Ocimum sanctum Linn. on normal and dexamethasone suppressed wound
      healing.
AB  - Ethanolic extract of leaves of O. sanctum was investigated for normal wound
      healing and dexamethasone depressed healing using incision, excision and dead
      space wound models in albino rats. The extract of O. sanctum significantly
      increased the wound breaking strength in incision wound model. The extract
      treated wounds were found to epithelialize faster and the rate of wound
      contraction was significantly increased as compared to control wounds.
      Significant increase in wet and dry granulation tissue weight, granulation tissue
      breaking strength and hydroxyproline content in dead space wound model was
      observed. The extract significantly decreased the antihealing activities of
      dexamethasone in all the wound models. The results indicated that the leaf
      extract promotes wound healing significantly and able to overcome the wound
      healing suppressing action of dexamethasone. Histological examination of
      granulation tissue to determine the pattern of lay-down for collagen confirmed
      the results.

PMID- 16430092
TI  - Air-breathing rhythm in Clarias batrachus (Linn.): modulatory role of eyes,
      pineal and exogenous melatonin.
AB  - Effects of enucleation followed by pinealectomy and administration of exogenous
      melatonin on air-breathing activity rhythm in a fresh water catfish, C. batrachus
      maintained at LD 12:12 and laboratary temperature during its prepratory phase,
      were examined. Results of cosinor analysis clearly reveal that most of the intact
      individuals exhibited circadian rhythm in their air-breathing activity and such
      rhythm persists even after enucleation followed by pinealectomy and then
      melatonin administration. However, the period (tau) of the activity obtained by
      power spectrum analysis was prominent 24 hr in most of the intact individuals,
      but it was increased (tau > 24 hr) after enucleation in most of the individuals.
      In most of the enucleated + pinealectomized individuals tau was less than 24 hr,
      and after receiving melatonin treatment tau was shifted to prominent 24 hr in
      most of the individuals. In addition, visual analysis of the actograms depicted
      that in intact individuals air-breathing activity is entrained with the timings
      of lights on/off with elevation of activity during dark period and decreased
      activity during light hours. However, enucleated and enucleated + pinealectomized
      individuals showed free run in their activity rhythm. The treatment of melatonin
      reestablished the entrainment of activity at least with the timing of lights off,
      in most of the studied individuals. Further, daily mean of the air-breathing
      activity was decreased in enucleated + pinealectomized individuals as compared
      with other studied groups (intact, enucleated, enucleated + pinealectomized +
      melatonin receiving). It could be speculated that there may be existence of
      extraretinal and extrapineal photoreceptors in C. batrachus. However, eyes play
      an important role in regulating air-breathing activity rhythm in such species. In
      addition, exogenous melatonin may also have some modulatory effect on such
      rhythm.

PMID- 16430093
TI  - Shrimps survive white spot syndrome virus challenge following treatment with
      Vibrio bacterin.
AB  - Taking an innovative approach, a vaccination study using five bacterial strains
      viz. Vibrio campbelli (B60), V. alginolyticus (B73), V. parahaemolyticus-like
      (B79), V. parahaemolyticus (R8) and V. harveyi (RG203) was conducted in Penaeus
      monodon against white spot syndrome virus (WSSV) infection, considered as one of
      the serious pathogens of shrimps. Oral challenge with shrimps infected with WSSV
      showed a relative percentage survival of 5 and 47% in the P. monodon juveniles
      vaccinated with V. parahaemolyticus and V. harveyi, respectively. Results showed
      that there is a possibility of specifically immunising the shrimps against WSSV
      using bacterin prepared out of Vibrio harveyi isolates taken from shrimps
      infected with WSSV. Also, there was a level of protection attained by the shrimps
      due to immunisation with Vibrio strains.

PMID- 16430094
TI  - Intraspecific strains of Pythium aphanidermatum induced disease resistance in
      ginger and response of host proteins.
AB  - Intraspecific strains of Pythium aphanidermatum induced resistance in ginger
      against rhizome rot and activated biosynthesis of selected host proteins. Pre
      inoculation of plants with IR strain (avirulent) or co-inoculation with SR2
      (virulent) caused significant reduction in disease severity. Analysis of protein
      profiles of ginger leaves of inoculated and non-inoculated plants by SDS-PAGE and
      Image Master VDS-ID Gel Analysis version : 3.0 revealed that some specific
      defence proteins/stress proteins increased in inoculated plants. Five such
      proteins having molecular weight 56, 32, 27, 18 and 14 kDa were detected in
      leaves of plant treated with IR + SR2 strains. On the contrary, mycelial protein
      profiles and submerged growth of strains were studied separately and together.
      Mycelia of IR, SR2 and IR + SR2 exhibited 26, 23 and 25 protein bands,
      respectively although, 21 bands were common between IR and SR2. Growth of SR2 in
      synthetic medium was much higher than that of IR, but the growth of two strains
      together was lower than SR2 alone. To characterise strains, their differential
      growth response to DL-beta-aminobutyric acid (BABA), a known defence activator of
      ginger was also tested. Results suggested that at least 5 specific defence
      proteins/stress proteins were involved in microbially induced resistance in
      ginger and inducer strains were distinct in their specific protein profiles and
      sensitivity to BABA.

PMID- 16430095
TI  - Biosorption of Ni, Cr and Cd by metal tolerant Aspergillus niger and Penicillium
      sp. using single and multi-metal solution.
AB  - Fungi including Aspergillus and Penicillium, resistant to Ni2+, Cd2+, and Cr6+
      were isolated from soil receiving long-term application of municipal wastewater
      mix with untreated industrial effluents of Aligarh, India. Metal tolerance in
      term of minimum inhibitory concentration (MIC) was 125-550 microg/ml for Cd, 300
      850 microg/ml for Ni and 300-600 microg/ml for Cr against test fungi. Two
      isolates, Aspergillus niger and Penicillium sp. were tested for their Cr, Ni and
      Cd biosorption potential using alkali treated, dried and powdered mycelium.
      Biosorption experiment was conducted in 100 ml of solution at three initial metal
      concentrations i.e., 2, 4 and 6 mM with contact time (18 hr) and pretreated
      fungal biomass (0.1g) at 25 degrees C. Biosorption of all metals was found higher
      at 4 mM initial metal concentration as compared to biosorption at 2 and 6 mM
      concentrations. At 4 mM initial metal concentration, chromium biosorption was
      18.05 and 19.3 mg/g of Aspergillus and Penicillium biomasses, respectively.
      Similarly, biosorption of Cd and Ni ions was also maximum at 4 mM initial metal
      concentration by Aspergillus (19.4 mg/g for Cd and 25.05 mg/g of biomass for Ni)
      and Penicillium (18.6 mg/g for Cd and 17.9 mg/g of biomass for Ni). In general,
      biosorption of metal was influenced by initial metal concentration and type of
      the test fungi. The results indicated that fungi of metal contaminated soil have
      high level of metal tolerance and biosorption properties.

PMID- 16430096
TI  - In vitro clonal propagation of Chlorophytum borivilianum Sant. et Fernand., a
      rare medicinal herb from immature floral buds along with inflorescence axis.
AB  - A novel method of shoot regeneration from immature floral buds along with
      inflorescence axis in C. borivilianum, a rare medicinal herb is described. Using
      this explant, axenic cultures were established with very less contamination
      (10%). MS medium with 2 mg l(-1) kinetin and 0.1 mg l(-1) 2, 4
      dichlorophenoxyacetic acid proved to be the best for multiple shoot induction.
      Maximum number (35) of shoot production was achieved in MS medium with 2 mg l(-1)
      benzylaminopurine. Rooting of shoots (86.7%) with maximum fasciculated roots (5)
      occurred on Knops medium containing iron and vitamins of MS medium with 2 mg l(
      1) indole-3-butyric acid and 0.1% activated charcoal. Plant survival was 80% in
      four weeks after their removal from in vitro conditions. Per explant 34 hardened
      plants generated within 50 weeks. This protocol can be useful for large-scale
      clonal multiplication from immature floral buds with inflorescence axis and
      successfully used for germplasm conservation of this rare medicinal herb without
      destroying the mother plant.

PMID- 16430097
TI  - Aluminium toxicity induced poikilocytosis in an air-breathing teleost, Clarias
      batrachus (Linn.).
AB  - The present study was undertaken to assess the toxicity of acid alone and two
      different sublethal concentrations of aluminium, (25% and 75% dose of 96 hr LC50
      value in acidified soft water of pH 5) on red blood cells of a stenohaline
      catfish, C. batrachus for an acute exposure of 5 days. The scanning electron
      microscopic studies on all the three treated groups revealed several kinds of
      erythrocyte alterations and modifications with abnormal morphology. These
      included abnormal surface-wrinkling accompanied with excessive roughness on the
      membrane, erythrocytes with surface granulation in higher dose and finally the
      appearance of morphologically abnormal forms, the codocyte (target cell) and the
      stomatocyte. The results suggest that abnormality in the shape of erythrocytes
      could be linked to altered surface membrane area to volume ratio, decrease in
      cytoplasmic volume owing to reduced Hb content or increase in the amount of water
      content within the cell resulting from osmotic disequilibrium. In this context,
      the abnormal surface membrane morphology could be attributed to cytoskeleton
      fragility and defects in structural proteins. Further, the acid group exhibited a
      striking behavior of cellular adhesion and bonding to adjoining cell surfaces,
      culminating in several bunches which thereby reduces the surface area for gaseous
      exchange and could produce blocking effect while flowing through
      microcirculation.

PMID- 16430098
TI  - Effect of T-2 toxin on growth, performance and haematobiochemical alterations in
      broilers.
AB  - Administration of dietary T-2 toxin in 120 days old broiler chicks led to
      significant lower body weights and increase in feed conversion ratio from 2nd
      week of age. There was significant reduction in haemoglobin and packed cell
      volume in T-2 toxicated birds at 4 ppm level only. The other hematological
      parameters like TEC, TLC and absolute leucocyte count did not showed any
      variation due to T-2 toxin in feed. Significant reduction in serum total protein
      and cholesterol levels and rise in serum uric acid and LDH levels of broilers
      were observed due to dietary T-2 toxin. The result suggests that T-2 toxin is
      toxic to broilers even at very low concentrations.

PMID- 16430099
TI  - [The ASCOT study: the end of the treatment of hypertension with beta-blockers?].

PMID- 16430100
TI  - [The relation of GERD, bronchial asthma and the upper respiratory tract].
AB  - Gastroesophageal reflux disease (GERD) is one of the most common diseases
      affecting upper gastrointestinal tract. It is a chronic disease, whith stadily
      growing incidence and prevalence in west countries during last 30 years. GERD is
      caused by pathologic gastroesophageal reflux (GER). GERD includes endoscopically
      positive, endoscopically negative and extraesophageal reflux disease.
      Extraesophageal symptoms of GERD have been of a growing attention and discussion
      during last few years. The most discussed topics are the relation of GERD and
      bronchial asthma (BA), chronic cough and symptomatology from ear, nose and
      throught (ENT) regions, but also non - cardial chest pain and many others. AIM:
      In our clinic we ran a 5 years study which aim was to evaluate the presence of
      GERD in patients with bronchial asthma, chronic cough and affections from ENT
      regions. To assess if 3 months GERD treatment would improve lung function,
      subjective complaints (cough) and GERD control in asthmatics; if this treatment
      would allow to step - down with antiasthma medication. To assess if 3 months GERD
      treatment can improve objective and subjective assessments in patients with
      chronic cough and findings in ENT regions. As for GERD, we evaluated the
      improvement of pH and subjective complaints (pyrosis). METHODS: We examined 86
      patients with different severity of bronchial asthma, 54 patients with chronic
      cough and 31 patients with ENT symptoms. All patients underwent 24 hour
      esophageal pH metry, spirometry with lung function evaluation and objective ENT
      examination by flexible laryngoscopy. In case of pathologic finding on 24 hour pH
      metry 3 months full antireflux treatment with proton pump inhibitors (PPI) and
      prokinetics was introduced. After 3 months of GERD treatment we performed control
      24 hour esophageal pH metry, control spirometry and ENT examination by flexible
      laryngoscopy. Patients were asked to make their subjective symptoms assessments.
      RESULTS: We found that GERD prevalence in patients with respiratory symptoms was
      very high. Three months GERD treatment improved lung function (FEV1) with
      statistical significance (p = 0.0319), and so improved GERD control (in 60.7% of
      patients with high statistical significance p = 0.0009). Subjective complaints
      (cough) also improved in most patients. 3 months GERD treatment did not allow to
      step down with maintenance BA therapy according to GINA guidelines, but it
      enabled to decrease the rescue medications in 50% of patients. Patients with
      chronic cough can benefit from GERD treatment as cough improved in 75.8% of
      patients. CONCLUSION: Objective findings as well as subjective complaints
      improved in 75% of patients with ENT symptomatology. GERD control (DeMeester
      score and pyrosis if present) was highly statistically significant in all three
      groups of patients. It is necessary to mention, that there is a high presence of
      nocturnal acid breakthrough (NAB) in patients with respiratory symptoms: 30.3 %
      in patients with bronchial asthma, 63.6 % in patients with chronic cough and 45 %
      of patients with ENT manifestations.

PMID- 16430101
TI  - Evaluation of labeling and content of probiotics available in the Czech Republic.
AB  - Probiotics are live cultures of mikroorganisms which are good for human health
      and are used in human medicine as a treatment. Advantageous effect on a human
      health was proved in many studies in Europe and in the USA. On the other hand,
      many studies described lack of information about products containing probiotics -
      in particular the real bacterial strain or quantity of bacteria. We tried to
      evaluate thirteen products containing probiotics available in the Czech Republic.
      In all cases the leaflets contained information about the species and amount of
      bacteria (from seven products containing more than one species of bacteria were
      only in two cases declared the quantity of particular bacteria, in five cases was
      declared just the total quantity of bacteria). The declared species of bacteria
      were cultured in all tested products. Concluding; the information on the leaflets
      of probiotic products is sufficient for a clinical practice and the real species
      and quantity of bacteria come up to declared data.

PMID- 16430102
TI  - [The influence of long-term growth hormone replacement therapy on body
      composition, bone tissue and some metabolic parameters in adults with growth
      hormone deficiency].
AB  - A syndrome of growth hormone deficiency in adults (GHDA) is a syndrome
      characterised by metabolic deviations, body composition abnormalities, fatigue,
      decreased quality of life and some cardiovascular changes. The aim of the study
      was to assess the influence of the growth hormone (GH) replacement therapy on
      body composition, bone changes, serum lipids levels and some parameters of sugar
      metabolism in the course of 7-year monitoring. We followed 34 individuals of mean
      age of 41.73 +/- 2.49 years (mean +/- SE). Severe deficiency of GH was
      demonstrated by performing stimulation insulin tolerance test. Duration of
      treatment was 4.13 +/- 0.36 years (mean +/- SE). Patients were examined before
      the initiation of replacement therapy, after 6 months and further in yearly
      visits. To determine a statistical level of significance in individual parameters
      we compared initial baseline status (before drug administration) with the status
      in individual time intervals. The body composition was examined by anthropometric
      methods, bioelectric impedance and by densitometry, bone changes were examined by
      means of DEXA. There were no statistically significant changes of weight, but the
      waist circumference significantly decreased (p < 0.05), as well as the sum of
      skinfold thickness (p < 0.05) within the whole treatment period. The percentage
      of body fat mass measured by the BIA method was significantly changed after the
      period of 3 years (p < 0.05). Upon the densitometrical measurement of the body
      composition a significant decrease in kilograms of body fat mass (FM) occurred in
      the first year of the treatment (p < 0.05) and an increase in lean body mass
      (LBM) in kilograms during our complete monitoring (p < 0.05). A statistically
      significant increase in bone density was found in the whole-body BMD and BMC
      after the first year of the treatment. In the examination of peripheral bone
      changes a statistically significant increase in BMD occurred (expressed as a Z
      score) in the area of proximal femur after the first year and collum femoris
      after three years (p < 0.05), there was a significant increase in BMD of the
      lumbar spine already after one year of the treatment (p < 0.05) and changes were
      significant also in further four years. There were found no statistically
      significant changes related to the sugar metabolism. In the field of lipid
      metabolism a decrease of total and LDL cholesterol occurred already after a half
      of the year of the treatment (p < 0.05), changes were significant also in further
      four years. HDL cholesterol levels have had a progressive tendency, but they were
      not statistically significant. Positive changes of body composition, an increase
      in bone density and a decrease of total and LDL cholesterol were demonstrated in
      the course of the growth hormone replacement therapy.

PMID- 16430103
TI  - [Influrence of recombinant human procalcitonin on phagocytic and candidacidal
      ability of polymorphonuclear leukocytes and on killing mechanisms of serum and
      blood aganist bacteria Staphylococcus aureus and Escherichia coli].
AB  - Procalcitonin (PCT) is a highly selective and specific marker for early diagnosis
      of sepsis. There is enough information confirming that procalcitonin should be
      considered as an important mediator in the pathophysiology of sepsis. The aim of
      our work was to evaluate the effect of recombinant human procalcitonin (rhPCT) on
      phagocytic and candidacidal activity of polymorphonuclear leukocytes (PMNL) in
      blood, as well as on killing mechanisms of fresh serum and blood against
      Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Our results
      show that rhPCT dose dependently decreased both phagocytic and candidacidal
      activity of polymorphonuclear leukocytes (p < 0.001). RhPCT inhibited also the
      microbicidal activity of both serum and blood on E. coli that was found by
      inoculation of suspension on culture plates. We found that rhPCT supported the E.
      coli colony count increase during the incubation in the presence of both serum
      and blood. The effect of rhPCT on the S. aureus colony count increase was not
      statistically significant. CONCLUSION: Our results indicate a suppressive effect
      of rhPCT on phagocytic and microbicidal activity of polymorphonuclear leucocytes.

PMID- 16430104
TI  - [Possibilities of ultrasonographic differentiation of neck and axillary
      lymphadenopathy].
AB  - Technical development of ultrasonography connected with improvement of resolving
      power has enlarged possibilities in detection and differentiation of lymph nodes.
      In the current clinical practice ultrasonic examination is most frequently
      requested for assessment of lymph nodes in neck and axillary regions in
      connection with inflammatory or tumour diseases. Although the final diagnosis
      must be confirmed histopathologically, there exist some echographic criteria
      enabling with a great probability to appoint the malignant character of lymph
      nodes: round shape expressed by the shape index near to 1, sharp edges,
      heterogeneous echostructure and mainly loss of the hilar sign. In highly enlarged
      lymph nodes these criteria can be completed by colour Doppler examination
      revealing a peripheral type of intranodal vascularity and increased value of
      impedance indices in supply artery (RI > 0.8, PI > 1.8).

PMID- 16430105
TI  - [Idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF), known in Europe as cryptogenic fibrosing
      alveolitis, is a rare, progressive and usually fatal form of idiopathic
      interstitial pneumonia. IPF is characterized by failure of alveolar re
      epithelization, persistence of fibroblasts, deposition of extracellular matrix,
      and distortion of lung architecture which ultimately results in respiratory
      failure. Current consensus statements reserve the term IPF to refer to a specific
      clinical entity associated with the histopatological pattern of usual
      interstitial pneumonia (UIP). UIP is characterized by temporal heterogeneity,
      with alternating areas of interstitial fibrosis, fibroblastic foci (areas of
      proliferating fibroblasts and myofibroblasts), inflammation, honeycomb lung, and
      normal parenchyma. Fibroblastic foci are associated with progressive disease.
      Treatment of IPF remains clinical problem. Currently, there is no conservative
      therapy improving the survival of patients. Lung transplantation, however,
      improves survival. Identification of pathways crucial to fibrogenesis might offer
      potentially novel therapeutic targets to slow or halt progression of IPF.

PMID- 16430106
TI  - [The idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia].
AB  - Idiopathic hypereosinophilic syndrome is a heterogenous group of hematological
      disorders characterized by eosinophilia (> 1.5 x 10(9)/l) persistent for more
      than 6 months, exclusion of reactive eosinophilia from other causes, such as
      parasitic infections or allergy, and evidence of end-organ damage. According to
      World Health Organization the exclusion includes all neoplastic disorders in
      which eosinophils are part of the neoplastic clone. Excluded should be also T
      cell population with aberant phenotype and abnormal cytokine production, recently
      considert also as "lymphocytic" variants of the HES [42]. HES has to be
      reclassified as chronic eosinophilic leukemia (CEL) when there is evidence for
      clonality based on the presence of chromosomal abnormalities or inactivation of X
      chromosome in female patients. The successful empiric treatment of patients with
      tyrosine kinase inhibitor imatinib (Glivec) suggested the presence of an imatinib
      sensitive tyrosine kinase inhibitor. The identification of a specific
      intersticial chromosome deletion del(4)(q12;q12) creating the FIP1L1-PDGFRA
      fusion gene confirmed this hypothesis. Patients carrying this gene should be
      reclassified as CEL and detection of this gene is a positive predictor for
      response to imatinib therapy. Effective doses of imatinib are 100 mg/day. The
      side effects are minimal. The only exception is an acute left ventricular
      dysfunction which has been reported in three patients within the first week of
      treatment with imatinib. Imatinib has been successfully used also in some
      patients with the constitutively activated thyrosine kinase ETV6-PDGFRbeta [1]
      and in systemic mast cell disease associated with eosinophilia. Other
      therapeutical options for HES/CEL have been mentioned. The resistence to imatinib
      and the possibilities how to overcome it are discussed.

PMID- 16430107
TI  - [Prevention of cardiovascular events by the antihypertensive treatment using
      amlodipine and perindopril in comparison with the use of atenolol and
      bendroflumethiazide. The ASCOT (Anglo-Scandinavian Outcomes Trail: blood pressure
      lowering arm) study results--multicentre, randomised, controlled trial. Landmark
      in the development of opinions on combination therapy in hypertension?
      (comment)].
AB  - It is a multicentre, prospective, randomised controlled trial in 19 257 patients
      with hypertension aged 40-79 years with at least three cardiovascular risk
      factors. After 5,5 years median follow-up fewer individuals on amlodipine +
      perindopril had a primary endpoint (429 vs 474, HR 0.90, p = 0.1052), fatal and
      non-fatal stoke (327 vs 422, HR 0.77, p = 0.0003), total cardiovascular events
      and procedures 1362 vs 1602, 0.84, p = 0.0001) and all cause mortality (738 vs.
      820, HR 0.89, p = 0.025). The incidence of developing diabetes was also less on
      the amlodipine + perindopril based regimen (567 vs 799, HR 0,70, p = 0.0001). The
      amlodipine-perindopril based regiment prevented more major cardiovascular events
      and induced less diabetes than the atenolol-based regimen. These results may have
      in implications with respect to optimum combinations of antihypertensive drugs.

PMID- 16430108
TI  - [Atypital localisation of pyoderma gangraenosum in patient with ulcerative
      colitis].
AB  - The authors present a case of 61-year-old man with ulcerative colitis and with
      extraintestinal manifestation of the disease in the form of pyoderma
      gangraenosum. Multiple skin defects, which developed in atypical localisation
      (extensive affection of facial and hairy parts of the head) in patient with
      chronically active form of ulcerative colitis were complicated with bacterial
      contamination of methicilin-resistant strains of Staphylococcus aureus. After
      application of the parenteral feeding, corticotherapy and targeted antibiotic
      therapy the subjective and objective status of the patient markedly improved,
      stool frequency was reduced, admixture of blood in the stool disappeared,
      temperatures fell back and there was a decrease in activity of non-specific bowel
      inflammation in laboratory findings. However endoscopic examination of the
      intestine confirmed the finding of chronically active ulcerative colitis with
      ulcerations and bridging polyps. Patient was indicated to total colectomy, but he
      refused it.

PMID- 16430109
TI  - [Diagnostics and treatment of hepatocellular carcinoma. Recommendations of the
      Portal Hypertension Working Group of the Czech Hepatology Society and the J.E.
      Purkinje Czech Medical Society ].
AB  - Hepatocellular carcionma (HCC) is almost exclusively associated with liver
      cirrhosis as a significant HCC risk marker in advanced countries. Applicable
      therapy depends on early diagnosis, and risk patients should be screened for the
      presence of HCC on a regular basis. Liver ultrasound and determination of alpha
      fetoprotein serum levels (AFP) are the screening methods used. Spiral CT is the
      most often used method for HCC staging. Non-invasive methods may under certain
      circumstances replace aimed biopsy. There are 3 basic curative therapies for the
      early stage of HCC: liver transplantation, surgical resection and different
      methods of local destruction of tumour (i.e., ethanolisation, thermoablation,
      etc.). Patients at medium stage of HCC may profit from chemoembolisation. Current
      available systemic chemotherapy is ineffective. Patients with advanced HCC are
      treated symptomatically. Patient survival prognosis after the application of one
      of the above treatment methods may be similar with that for HCC free cirrhosis
      patients, however, prognosis for advanced HCC patients is bad, with survival
      period from one to nine months.

PMID- 16430110
TI  - [Food intolerance--a cause or a consequence of digestive disorders?].

PMID- 16430111
TI  - [The benefit of pioglitazone in patients with diabetes mellitus type 2 and
      cardiovascular complications].

PMID- 16430112
TI  - [200 years since of the birth of Josef Skoda (10. 12. 1805--13. 6. 1881)].

PMID- 16430113
TI  - [Fundamental studies carried in Institute on occupational medicine and human
      ecology, application of the results into practical health care].

PMID- 16430114
TI  - [Occupational risk factors and reproductive health of female workers engaged into
      kraft pulping].
AB  - Female workers of child-bearing age appeared to have significant frequency of
      reproductive disorders, high degree of their connection with the occupation. The
      authors justified a concept of reproductivity disorders formation.

PMID- 16430115
TI  - [Evaluation of risk connected with occupational and industrial diseases in
      firemen].
AB  - The authors defined indexes of risk connected with occupational and industrial
      diseases, that helped to justify associations of some nosologic entities specific
      for firemen.

PMID- 16430116
TI  - [Methodic base to organize monitoring of mercury jeopardy].
AB  - The authors consider approach to complex monitoring of mercury jeopardy, based on
      experience of research workers in Irkutsk region.

PMID- 16430117
TI  - [Psychophysiologic characteristics of students training in aircrafts
      construction].
AB  - The authors presented materials on several parameters of psychophysiologic state
      in technical college students--potential staffers in aviation enterprises. The
      authors calculated risks of major pathology syndromes, evaluated level of somatic
      health, studied memory and intellectual sphere and physical development of the
      students.

PMID- 16430118
TI  - [Pathogenetic role of immune reactivity disorders in mechanisms underlying
      relations between hypothalamus-hypophysis-adrenals and thyroid systems in
      vibration disease].
AB  - Studies of immune and hormonal state in patients with vibration disease caused by
      general and local vibration helped to evaluate pathogenetic role of immune
      reactivity disorders in mechanisms underlying relations between hypothalamus
      hypophysis-adrenals and thyroid systems, to specify principal scheme of
      interactions between neuroendocrine and immune systems in such disorders.

PMID- 16430119
TI  - [Peripheral nerves disorders under exposure to metallic mercury and complex of
      toxic chemicals].
AB  - Examination of patients with chronic mercury poisoning and fire men subjected to
      complex of toxic chemicals during fire extinguishing revealed subclinical latent
      disorder of peripheral nerves due to chronic mercury intoxication and clinical
      manifestations of polyneuropathy involving nerves of upper and lower limbs in
      firemen.

PMID- 16430120
TI  - [Features of biochemical parameters in firemen].
AB  - The authors present results of examinations covering firemen with varying length
      of service and intensity of chemical load. Those results prove lower amount of
      alpha1-globulines and increased beta1-globulines content. Lipid metabolism
      disorders in idividuals with lower frequency of fires attended are caused by
      discrepancy between hormonal demands in stress expectation and actual utilization
      of energy substrates by various body tissues.

PMID- 16430121
TI  - [Microflora and cytological status of mouth caviti mucoid membrane and nose among
      firemen].
AB  - The authors presented qualitative and quantitative evaluation of micro
      biocenoses, studied cytologic and morphologic parameters of upper respiratory
      tract mucosa, evaluated concentrations of SigA in firemen saliva. Results are
      lower nonspecific anti-infectious resistance due to exposure to occupational
      hazards.

PMID- 16430122
TI  - [Markers of impact and effects of dioxines in firemen who participated in fire
      extinguishing at "Irkutskcabel" plant].
AB  - The article contains data tracing connection between CYP1A2 activity, dioxines
      level and dioxine-sensitive genes expression in firemen who participated in fire
      extinguishing at cabel plant.

PMID- 16430123
TI  - The acupuncture randomised trial (ART) for tension-type headache--details of the
      treatment.
AB  - OBJECTIVE: The goal of this paper is to describe the characteristics of
      physicians and their interventions in a large, multicentre randomised trial of
      acupuncture for tension-type headache known as ART TTH, in order to enable
      acupuncturists to assess the study interventions. METHODS: Participating
      physicians were recruited whose qualifications met or surpassed those of
      physicians currently accredited for providing acupuncture by state health funding
      agencies in Germany. Semi-standardised treatment strategies for acupuncture and
      minimal acupuncture were developed in a consensus process with acupuncture
      experts. A total of 270 patients suffering from episodic or chronic tension-type
      headache were randomised to 12 sessions of semi-standardised acupuncture (three
      predefined 'basic' points, recommendations for additional points given, but
      individual choice of additional points possible), standardised minimal
      acupuncture (superficial needling of at least 5 of 10 predefined, bilateral,
      distant non-acupuncture points) or a waiting list. Forty two physicians, trained
      and experienced in acupuncture, from 28 centres in Germany participated in the
      trial. RESULTS: The median duration of acupuncture training of trial physicians
      was 500 hours (range 140 to 1350 hours). Physicians had 10 (< 1 to 25) years
      acupuncture experience. The three 'basic' points (GB20, GB21 and LR3) were
      treated in 96%, 82% and 97% of sessions, respectively. Frequently treated
      optional points included LI4 (67%), SP6 (50%) and ST36 (46%). Ten of the 42
      physicians stated that they would have treated patients differently outside the
      trial. The trial found a significant effect of acupuncture over waiting list but
      not over minimal acupuncture. CONCLUSIONS: In general, trial physicians complied
      well with the predefined interventions. A relevant minority of participating
      trial physicians stated that they would have treated patients differently outside
      the trial.

PMID- 16430124
TI  - Effects of lumbar acupuncture stimulation on blood flow to the sciatic nerve
      trunk--an exploratory study.
AB  - INTRODUCTION: Acupuncture may have a role in the treatment of intermittent
      claudication of the cauda equina due to lumbar spinal canal stenosis. The aim of
      this study was to explore the possible physiological mechanisms. METHODS: In a
      laboratory experiment, manual acupuncture was performed at a point adjacent to
      the sixth lumbar vertebra of 13 animals and its effect on sciatic nerve blood
      flow was measured using a laser Doppler flowmetry. Simultaneously, changes in
      blood pressure and cardiac rate were observed. Each animal was stimulated four to
      eight times, making a total of 58 experiments. RESULTS: Acupuncture stimulation
      did not produce consistent changes in sciatic nerve blood flow, with increased
      and decreased blood flow as well as no change in blood flow observed. Among the
      58 individual experiments, sciatic nerve blood flow was increased in 33, reduced
      in 12, and unchanged in 13. Approximately half of the stimulations showed a
      correlation between blood flow and blood pressure change. CONCLUSION: Our results
      indicate that lumbar acupuncture stimulation can have an influence on sciatic
      nerve blood flow. The effect is dependent not only on blood pressure but also
      other factors, for example vasodilator and vasoconstrictor nerve activity. This
      mechanism may contribute to a clinical effect on intermittent claudication of the
      cauda equina.

PMID- 16430126
TI  - Conducting and reporting case series and audits--author guidelines for
      acupuncture in medicine.
AB  - This article aims to give guidance on the conduct and reporting of case series
      and audits of acupuncture, based on common problems that have arisen in the past.
      This type of project, and particularly the prospective case series or pre- post
      intervention study, may give valuable evidence of the overall effectiveness of
      acupuncture--for example in different situations and in different conditions--
      and provides one step in the research pathway before generating an hypothesis.
      The project should be designed with the aim of reducing bias as much as possible.
      Careful and detailed planning is essential for the project to produce worthwhile
      results that readers can evaluate and replicate. Ethical issues should be
      considered and formal approval may be necessary. The patient group should be
      recruited systematically and baseline data obtained. The treatment given should
      be systematic and decisions to change or end treatment made explicit. The outcome
      should be measured in ways that are known to be reliable and valid.
      Musculoskeletal problems can be evaluated with scales for pain and confirmed by
      measuring one other symptom such as stiffness or one other aspect such as
      bothersomeness. Global change scores also provide supporting information, and the
      MYMOP (Measure Yourself Medical Outcome Profile) measure is popular when patients
      with different conditions are included. The design of questionnaires for beliefs
      and attitudes is a specialised area that should not be attempted without expert
      help. Adverse events should also be recorded. Analysis of the data and the best
      way of summarising and presenting the results are also discussed.

PMID- 16430125
TI  - Acupuncture and self acupuncture for long-term treatment of vasomotor symptoms in
      cancer patients--audit and treatment algorithm.
AB  - INTRODUCTION: Since hormone replacement therapy given for long periods is now
      recognised to produce serious side effects, patients with troublesome vasomotor
      symptoms are increasingly using non-hormonal treatment including acupuncture.
      Several randomised controlled trials have shown that acupuncture reduces
      menopausal symptoms in patients experiencing the normal climacteric. It may have
      this effect by raising serotonin levels which alter the temperature set point in
      the hypothalamus. Vasomotor symptoms can be extreme in breast cancer patients and
      patients with prostate cancer who are undergoing anticancer therapy. The safety
      of some herbal medicines and phytoestrogens has been questioned, as they could
      potentially interfere adversely with the bioavailability of tumouricidal drugs. A
      previous study reports short term benefit from acupuncture, and the aim of this
      report is to describe our approach to long term treatment. ACUPUNCTURE APPROACH:
      After piloting several approaches, six weekly treatments were given initially at
      LI4, TE5, LR3 and SP6 and two upper sternal points, but avoiding any limb with
      existing lymphoedema or prone to developing it. If there were no
      contraindications, patients were given clear instructions on how to perform self
      acupuncture using either semi-permanent needles or conventional needling at SP6,
      weekly for up to six years, for long term maintenance. AUDIT METHODS AND RESULTS:
      A retrospective audit of electronic records was carried out by a doctor not
      involved in treatment. A total of 194 patients were treated, predominantly with
      breast and prostate cancer. One hundred and eighty two patients were female. The
      number of pre-treatment hot flushes per day was estimated by the patient: in the
      159 cases providing adequate records, the mean was 16 flushes per day. Following
      treatment, 114 (79%) gained a 50% or greater reduction in hot flushes and 30
      (21%) a less than 50% reduction. Treatment was abandoned in those who responded
      poorly or not at all. The duration of treatment varied from one month to over six
      years with a mean duration of nine months. Seventeen patients (9%) experienced
      minor side effects over the six year period, mostly minor rashes; one patient
      described leg swelling but this was likely to be due to a concurrent fracture.
      CONCLUSION: Acupuncture including self acupuncture is associated with long-term
      relief of vasomotor symptoms in cancer patients. Treatment is safe and costs
      appear to be low. An algorithm is presented to guide clinical use. We recommend
      the use of self acupuncture with needles at SP6 in preference to semi-permanent
      needles in the first instance, but poor responders use indwelling studs if they
      fail to respond adequately to self acupuncture with regular needles. Point
      location may be of less importance than the overall 'dose', and an appropriate
      minimum dose may be required to initiate the effect.

PMID- 16430127
TI  - Acupuncture for treatment of the yips?--a case report.
AB  - A 65 year old golfer with the yips was treated with acupuncture at GV20, EX-HN-1
      (Si Shen Cong) and TE5. The symptoms disappeared after one treatment and no
      relapse has occurred in the 24 months' follow up. Although it cannot be
      determined whether the effect in this case occurred from neurological stimulation
      or was the result of expectation, acupuncture may be worth trying in patients
      with the yips since this condition is otherwise difficult to treat.

PMID- 16430128
TI  - A tale of two foxes--case reports: 1. Radial nerve paralysis treated with
      acupuncture in a wild fox. 2. Acupuncture in a fox with aggressive and obsessive
      behaviour.
AB  - Case 1. This is believed to be the first report of acupuncture treatment for
      traumatic radial nerve paralysis in a wild fox. From the first treatment,
      improvement in the range of mobility and sensation of the limb was evident.
      Additionally, the attitude of this wild animal changed from fear and aggression
      to complete cooperation: he lay peacefully during every treatment in a calm,
      drowsy state. Case 2. This reports the calming effects of acupuncture on a fox
      which had been showing aggressive behaviour and obsessive circling following
      toxoplasma infection.

PMID- 16430129
TI  - S-layers as patterning elements for application in nanobiotechnology.
AB  - Two-dimensional bacterial cell surface layer protein crystals (S-layers) are the
      most commonly observed cell surface structure in bacteria and archaea. Isolated S
      layer proteins have the intrinsic tendency to self-assemble into crystalline
      arrays in suspension and on various interfaces. Basic research on the structure,
      genetics, chemistry, morphogenesis and function of S-layers has led to a broad
      spectrum of applications in nanotechnology and biomimetics. The possibility to
      change the properties of S-layer proteins by genetic engineering opens new ways
      for tuning their functional and structural features. Functionalized S-layer
      proteins that maintain their ability to self-assemble have led to new affinity
      matrices, diagnostic tools, vaccines or biocompatible surfaces, as well as to
      biological templating or specific biomineralisation strategies at surfaces.

PMID- 16430130
TI  - DNA as nanoscale building blocks.
AB  - The use of DNA as programmable building blocks to achieve highly-definable
      nanostructures, termed as DNA nanotechnology, has offered great opportunities to
      control matter at a very small scale. Fast growing researches along this
      direction has led to the emergence of several significant branches of DNA
      nanotechnology. This review intends to summarize the recent developments in this
      area. Several topics will be discussed with a focus on the works from the
      authors' group, including (1) DNA self-assembly and DNA-directed self-assembly,
      (2) DNA nanomachines, (3) DNA-based electronics, (4) DNA assisted
      nanofabrications, and (5) DNA computations.

PMID- 16430133
TI  - Single molecule fluorescence control for nanotechnology.
AB  - Nanoscience and nanotechnology are providing fresh approaches to engineer
      materials with practical applications such as molecular-sized therapeutic and
      diagnostic devices, drug delivery vehicles, environmental sensors, high-rate
      manufacturing platforms, and self-assembling nanomachines. In many cases,
      researchers are mimicking biological systems that easily achieve molecular scale
      control through directed self-assembly. In parallel, a revolution has occurred in
      the basic sciences, which utilizes recent advances in fluorescence microscopy to
      achieve single molecule detection capability. The future will see a merger of
      these two separate research thrusts, as single molecule detection will afford
      optimal control over the assembly and performance of individual nanoscale
      devices.

PMID- 16430132
TI  - RNA helicases: versatile ATP-driven nanomotors.
AB  - RNA helicases are a large family of molecular motors that utilize nucleoside
      triphosphates to unwind RNA duplexes and to remodel RNA protein complexes. In
      this review, we discuss the structure and function of RNA helicases with an
      emphasis on the potential application of these enzymes to control conformational
      changes in nanoassemblies that contain RNA.

PMID- 16430134
TI  - Pharmacological and anti-tumor activities of ganoderma spores processed by top
      down approaches.
AB  - Ganoderma was considered to be the most valuable medicine in ancient China, and
      it is still widely esteemed as a valuable health supplement and herbal medicine
      for the prevention and treatment of a variety of chronic diseases. However, the
      efficiency of Ganoderma in therapy has long been hindered by the uncertainty of
      its effectual constituents and the pharmaceutical mechanisms. Lately, it has been
      found that a most effective pharmaceutical component is the Ganoderma spore.
      Nevertheless, efficiency in using the spores requires further improvement in
      processing since the spores have rigid and tough walls the size on a micron scale
      which are difficult to take up and absorb by the human body. This review
      describes the top-down approaches in Ganoderma spore processing in order to
      release the effective pharmaceutical constituents such as the triterpenoid. The
      production of raw Ganoderma spores, the processing techniques to produce the
      sporoderm-broken germinating Ganoderma spores, the significant pharmacological
      activities of Ganoderma, the anti-tumor mechanisms elucidated by modern
      pharmacological studies, the outcome of the clinical trials, and a prospective of
      future preparations of triterpenoid-enriched Ganoderma spores and Ganoderma
      triterpenoids for immune regulation and cancer therapy will be discussed.

PMID- 16430135
TI  - Single-particle light microscopy of bacteriophages.
AB  - Bacteriophage capsids have a protein shell with a symmetrical, fullerene-like
      arrangement of subunits. In the case of double-stranded DNA bacteriophages, the
      capsid joins with accessory proteins to form a DNA packaging motor that packages
      a genome in a cavity of the capsid. The motor cleaves ATP to obtain the needed
      energy. Light microscopy of single bacteriophages and single bacteriophage DNA
      packaging intermediates is being developed for the following reasons: (1) A
      synchronization-independent, fractionation-independent procedure is needed for
      the in vitro analysis of bacteriophage DNA packaging motors. (2) A non-biological
      procedure is needed for identifying and characterizing new bacteriophages needed
      for studies of bacteriophage gene homologies. In a recent study, light microscopy
      based nanometry is used to follow the in vitro packaging of DNA in real time.
      Fluorescence microscopy of stained DNA is similarly used. Towards a more thorough
      analysis by fluorescence microscopy, single bacteriophage capsids are visualized
      by the unenhanced fluorescence of covalently bound protein-specific dyes.
      Dimerization of capsids is observed in real time. The dimerizing capsids had been
      restricted to a thin planar zone so that single-particle tracking was performed
      before, during, and after dimerization. Photobleaching is not a major problem.
      Thermal motion-based procedures are used for distinguishing binding from
      accidental co-migration. The long-range objective is the simultaneous real time
      monitoring of multiple state variables during cycling of a single DNA packaging
      motor. The results of these basic studies are applicable to both
      nanotechnological drug delivery and biological therapy.

PMID- 16430136
TI  - Packaging of gold particles in viral capsids.
AB  - In-vitro self-assembly conditions known to result in generating infectious
      virions have been used in vitro to reassemble bromovirus capsid proteins around
      negatively charged gold nanoparticles cores. We discuss here the optical
      properties (elastic light scattering) and the influence of the core size and of
      the functional moiety on the resulting virus-like particles. Our results indicate
      that the formation of a closed shell, as opposed to an amorphous protein coat,
      does occur and that the shell/core interactions can be tuned using different
      coatings on the nanoparticle core. Such studies may lead to real-time monitoring
      of viral traffic on the scale of a single virus, as well as to the possibility of
      chemical sensing along the intracellular and intercellular viral pathways and
      contribute to a better understanding of the virus transport and cellular
      compartmentalization.

PMID- 16430131
TI  - RNA nanotechnology: engineering, assembly and applications in detection, gene
      delivery and therapy.
AB  - Biological macromolecules including DNA, RNA, and proteins, have intrinsic
      features that make them potential building blocks for the bottom-up fabrication
      of nanodevices. RNA is unique in nanoscale fabrication due to its amazing
      diversity of function and structure. RNA molecules can be designed and
      manipulated with a level of simplicity characteristic of DNA while possessing
      versatility in structure and function similar to that of proteins. RNA molecules
      typically contain a large variety of single stranded loops suitable for inter-
      and intra-molecular interaction. These loops can serve as mounting dovetails
      obviating the need for external linking dowels in fabrication and assembly. The
      self-assembly of nanoparticles from RNA involves cooperative interaction of
      individual RNA molecules that spontaneously assemble in a predefined manner to
      form a larger two- or three-dimensional structure. Within the realm of self
      assembly there are two main categories, namely template and non-template.
      Template assembly involves interaction of RNA molecules under the influence of
      specific external sequence, forces, or spatial constraints such as RNA
      transcription, hybridization, replication, annealing, molding, or replicas. In
      contrast, non-template assembly involves formation of a larger structure by
      individual components without the influence of external forces. Examples of non
      template assembly are ligation, chemical conjugation, covalent linkage, and
      loop/loop interaction of RNA, especially the formation of RNA multimeric
      complexes. The best characterized RNA multiplier and the first to be described in
      RNA nanotechnological application is the motor pRNA of bacteriophage phi29 which
      form dimers, trimers, and hexamers, via hand-in-hand interaction. phi29 pRNA can
      be redesigned to form a variety of structures and shapes including twins,
      tetramers, rods, triangles, and 3D arrays several microns in size via interaction
      of programmed helical regions and loops. 3D RNA array formation requires a
      defined nucleotide number for twisting and a palindromic sequence. Such arrays
      are unusually stable and resistant to a wide range of temperatures, salt
      concentrations, and pH. Both the therapeutic siRNA or ribozyme and a receptor
      binding RNA aptamer or other ligands have been engineered into individual pRNAs.
      Individual chimeric RNA building blocks harboring siRNA or other therapeutic
      molecules have been fabricated subsequently into a trimer through hand-in-hand
      interaction of the engineered right and left interlocking RNA loops. The
      incubation of these particles containing the receptor-binding aptamer or other
      ligands results in the binding and co-entry of trivalent therapeutic particles
      into cells. Such particles were subsequently shown to modulate the apoptosis of
      cancer cells in both cell cultures and animal trials. The use of such antigen
      free 20-40 nm particles holds promise for the repeated long-term treatment of
      chronic diseases. Other potentially useful RNA molecules that form multimers
      include HIV RNA that contain kissing loop to form dimers, tecto-RNA that forms a
      "jigsaw puzzle," and the Drosophila bicoid mRNA that forms multimers via "hand-by
      arm" interactions. Applications of RNA molecules involving replication, molding,
      embossing, and other related techniques, have recently been described that allow
      the utilization of a variety of materials to enhance diversity and resolution of
      nanomaterials. It should eventually be possible to adapt RNA to facilitate
      construction of ordered, patterned, or pre-programmed arrays or superstructures.
      Given the potential for 3D fabrication, the chance to produce reversible self
      assembly, and the ability of self-repair, editing and replication, RNA self
      assembly will play an increasingly significant role in integrated biological
      nanofabrication. A random 100-nucleotide RNA library may exist in 1.6 x 10(60)
      varieties with multifarious structure to serve as a vital system for efficient
      fabrication, with a complexity and diversity far exceeding that of any current
      nanoscale system. This review covers the basic concepts of RNA structure and
      function, certain methods for the study of RNA structure, the approaches for
      engineering or fabricating RNA into nanoparticles or arrays, and special features
      of RNA molecules that form multimers. The most recent development in exploration
      of RNA nanoparticles for pathogen detection, drug/gene delivery, and therapeutic
      application is also introduced in this review.

PMID- 16430137
TI  - Engineering thermal stability in RNA phage capsids via disulphide bonds.
AB  - The RNA bacteriophages, a group that includes phages Qbeta and MS2, have a number
      of potential bionanotechnological applications, including cell specific drug
      delivery and as substrates for the formation of novel materials. Despite
      extensive sequence identity between their coat protein subunits, and an almost
      identical three-dimensional fold, Qbeta and MS2 capsids have dramatically
      different thermal stabilities. The increased stability of Qbeta has been
      correlated with the inter-subunit disulphide bonds present in that capsid and not
      present in MS2. We have tested this hypothesis directly using mass spectrometry.
      Analysis of the dissociated coat protein subunits suggests that inter-molecular
      disulphides are formed at the capsid five-fold but may not be at the three-fold
      axes. This conclusion has been tested by engineering disulphide cross-links into
      either the five-fold or three-fold positions of the recombinant MS2 capsid. Five
      fold cross-linking results in a mutant with stability properties similar to those
      of Qbeta. Three-fold cross-linking results in a mutant unable to assemble T = 3
      shells, implying that five-fold structures are on pathway to capsid assembly in
      these phages. The results demonstrate how it is possible to redesign the physical
      properties of phage shells and may be of general relevance to future applications
      of viruses and virus-like particles.

PMID- 16430138
TI  - Nanoscale biomimetics: fabrication and optimization of stability of peptide-based
      thin films.
AB  - The method of thin film preparation known as layer-by-layer assembly is of
      growing interest for current and envisioned developments in bionanotechnology.
      Here, cysteine-containing 32mer peptides have been designed, synthesized,
      purified, and used to prepare polypeptide films. A range of methods-quartz
      crystal microbalance, Fourier transform infrared spectroscopy, circular dichroism
      spectroscopy, and high-performance liquid chromatography-have been used to probe
      the effect of ionic strength and polymer secondary structure in solution on
      peptide self-assembly, and on secondary structure formation and disulfide bond
      cross-linking in the multilayer film. The amount of designed peptide deposited
      per adsorption step of film fabrication increased with increasing ionic strength,
      as with conventional polyelectrolytes. Secondary structure content changed from
      random coil to beta sheet on incorporation of peptides into a film. "Peptide
      inherent" cross-linking by disulfide bond formation increased film stability at
      acidic pH. Conditions for disulfide stabilization have been optimized. The
      results contribute to exploration of the physical basis of peptide self-assembly
      broaden the scope of applications of layer-by-layer assembly, particularly where
      biocompatibility and stability are key design concerns, and provide a basis for
      mass production of custom polypeptide thin films of high stability, even in harsh
      environments.

PMID- 16430139
TI  - Adsorption of a microtubule on a charged surface affects its disassembly
      dynamics.
AB  - The dynamics of disassembly of microtubules deposited on surfaces is shown to be
      strongly dependent on the electrostatic interaction between the microtubule and
      the substrate. Fluorescence microscopy of microtubules adsorbed on a Poly-L
      Lysine film and immersed in pure water show a drastic decrease in disassembly
      velocity compared to the microtubules in bulk water solutions. While microtubules
      suspended in pure water disassemble in seconds, the dissociation velocity of
      microtubules adsorbed on a Poly-L-Lysine film ranges from 0.8 to 1.0 microm/min
      in pure water. Kinetic Monte Carlo simulations of the microtubule dynamics
      indicate that a decrease in the dissociation velocity of unstable microtubules
      can be achieved by reducing the heterodimer dissociation rate constant of tubulin
      heterodimers constituting a single protofilament, adsorbed to the Poly-L-Lysine
      film. This model suggests that the reduction of the dissociation velocity
      originates from the electrostatic interactions between the positively charged
      amino groups of the Poly-L-Lysine film and the negatively charged microtubule
      surface.

PMID- 16430140
TI  - Optical nanobiosensor for monitoring an apoptotic signaling process in a single
      living cell following photodynamic therapy.
AB  - Optical nanobiosensors have enabled bioanalytical measurements to be undertaken
      within volumes as small as that of single biological cells. In this work, we use
      nanobiosensors to monitor a molecular signaling process, i.e., caspase-7
      activation, following photodynamic therapy (PDT) induced apoptosis in breast
      cancer cells (MCF-7). PDT induces the mitochondrial pathway of apoptosis which
      triggers cytochrome c release, activation of caspases-9, -8 and -7 and cleavage
      of poly (ADP-ribose) polymerase (Parp) protein. Caspase-7 is an important
      apoptosis-related cysteine protease involved in the activation cascade of
      caspases and in the proteolytic cleavage of Parp protein. Caspase-7 was detected
      and identified intracellularly using optical nanobiosensors. Our results show the
      detection of caspase-7 in single living MCF-cells which in essence typifies the
      apoptotic event induced by a PDT drug. This work, in principle, demonstrates the
      minimally invasive capability of optical nanobiosensors to measure important
      signaling molecules and events in pathways at the single cell level.

PMID- 16430141
TI  - Assemblies of concanavalin A onto carboxymethylcellulose.
AB  - The immobilization of Concanavalin A, (Con A), onto flat surfaces formed by
      ultrathin films of carboxymethylcellulose, CMC, silicon wafers or spin-coated
      poly(methyl methacrylate), (PMMA), was studied by ellipsometry, contact angle
      measurements and atomic force microscopy (AFM). The formation of Con A monolayer
      was only observed onto CMC films. The adsorption constant of Con A onto CMC films
      was determined as being (2.1+/-0.2) x 10(6) L mol(-1). After assembling Con A
      onto CMC surfaces, these became more hydrophobic, indicating a molecular
      orientation of Con A hydrophilic residues to the polysaccharide and Con A
      hydrophobic residues to the air. The affinity of Con A for hydroxyl rich silicon
      surfaces or for more hydrophobic PMMA films was very weak, evidencing that
      nonspecific interactions play a marginal role. For comparison, the immobilization
      of Con A onto hybrid particles of PMMA/CMC was investigated by means of UV
      spectrophotometry. Such particles carry CMC chains attached to the surface, as
      evidenced by mean zeta potential value of -40 mV. The adsorption constant
      determined for Con A onto PMMA/CMC particles was one order of magnitude smaller
      than that found for Con A onto CMC films. This finding indicates that the
      substrate geometry might influence the molecular arrangement of sugar residues on
      the surface, consequently affecting the sugar-Con A interaction (cluster effect).

PMID- 16430142
TI  - Fast fourier transform analysis of pore pattern in anodized alumina formed at
      various conditions.
AB  - A quantitative investigation of the effect of process parameters such as
      electrolyte concentration, temperature, anodization duration and anodization
      potential on the pore pattern (including pore diameter and distribution) in
      anodic alumina was performed based on aluminum anodization experiments. Using
      fast Fourier transform (FFT) analysis, we developed a method to quantify the
      orderedness of pore distribution. We found that at a lower temperature the
      anodization protocol of a 1 hr first step followed by a 4 hr second step did not
      cause any change in pore orderedness as opposed to the anodization protocol of a
      12 hr first step followed by a 1 hr second step, but at a higher temperature the
      former improved the pore orderedness. Increasing the electrolyte concentration,
      improved the pore orderedness. Varying the electrolyte concentration,
      temperature, and anodization duration did not have any effect on the pore
      diameter. Increasing the anodization potential, however, not only improved the
      pore orderedness but also increased the pore diameter. Linear relationships exist
      between the pore diameter and anodization potential and between the center to
      center pore spacing and applied anodization potential.

PMID- 16430143
TI  - Anomalous magnetic properties of mechanically milled cobalt oxide nanoparticles.
AB  - Defect induced magnetic properties of CoO nanoparticles produced via mechanical
      ball milling have been assessed by detailed magnetic measurements. A progressive
      decrease in the particle size and a concomitant increase in the induced strain
      have been observed with the milling times. The mechanically milled nanoparticles
      of CoO exhibit anomalous magnetic properties such as FM hysteresis when compared
      with the unmilled CoO sample. The presence of weak ferromagnetism, with a highest
      value of magnetization of 0.532 emu/g at 10 K in the 100 h milled sample, is
      attributed to the uncompensated surface spins resulting from induced surface
      defects via mechanical milling. The ZFC coercive force, measured at 10 K,
      increases with milling time reaching a maximum value of 1066 Oe for the 100 h
      milled sample. The temperature dependent field-cooled (FC) and zero-field-cooled
      (ZFC) magnetic measurements indicate a presence of an exchange bias field arising
      from uncompensated moments generated by mechanical strain and the
      antiferromagnetic (AFM) core. The exchange bias field measured at 10 K reaches a
      value 210 Oe for the 50 h milled sample and decreases upon prolonged milling. The
      exchange bias field vanishes at a temperature approximately 200 K, a temperature
      much lower than the Neel temperature of CoO (TN approximately 291 K). The
      observed anomalous magnetic behavior of CoO could be interpreted in terms of the
      exchanged bias FM-AFM model.

PMID- 16430144
TI  - Magnetic properties of magnetically soft nanocomposite Co-SiO2 prepared via
      mechanical milling.
AB  - Nanocomposite of Co-SiO2, a soft magnetic material, with Co weight fraction x =
      0.3 and 0.7 was prepared via mechanical milling. The magnetic properties of these
      samples, both zero-field-cooled (ZFC) and field-cooled (FC), have been measured
      as a function of x, milling time, and temperature. The structural assessment of
      the composite indicates a presence of only ferromagnetic (FM) hcp-Co phase in the
      composite. However, reported magnetic properties of these composites appear to be
      dependent on the presence of antiferromagnetic (AFM) phases of cobalt oxide as
      well. The observed enhancement in ZFC coercivity and a reduction in saturation
      magnetization with the milling time are due to an increase in defect density upon
      milling. The ZFC coercivity for the x = 0.3 samples has been found to be much
      higher than the x = 0.7 samples for all milling times. The coercivity above 50 K
      depends on temperature according to the law corresponding to isotropic uniaxial
      superparamagnetic particles. Below 50 K the presence of an AFM phase Co3O4 (TN
      approximately 33 K) and increased interparticle interactions bring in a departure
      from that law. The saturation magnetization is found to be temperature dependent
      for the x = 0.3 samples and temperature independent for the x = 0.7 samples,
      which further provides evidence of the presence of higher AFM phase fraction in
      the composite with a low metal volume fraction. The FC magnetic measurements show
      a presence of an exchange bias field and an enhanced coercivity which are higher
      than the ZFC measurements. All magnetic measurements indicate that the overall
      magnetic properties of the composite are dictated by the presence of a trace
      amount of cobalt oxides.

PMID- 16430145
TI  - Single-crystal CdSe nanowires prepared via vapor-phase growth assisted with
      silicon.
AB  - Hexagonal cadmium selenide (CdSe) nanowires, with diameter around 20 nm, were
      synthesized using a simple vapor-phase growth. Silicon (Si) powder acts as a
      source material assisting the synthesis, which is very important to the formation
      of the CdSe nanowires. We also suggest that self-catalysis at the Cd-terminated
      (0001) surface, together with the assistance action of Si, leads to the formation
      of wire-like structures to be formed. Meanwhile, the assistance of Si is
      responsible for the fineness and uniformity of the CdSe nanowires. The possible
      growth mechanism of the CdSe nanowires is proposed, and the optical property of
      the as-grown CdSe nanowires is characterized.

PMID- 16430146
TI  - Nucleation and growth of catalyst-free zinc oxide nanostructures.
AB  - This paper deals with the investigations on the nucleation and growth of Zinc
      Oxide (ZnO) nanostructures in a catalyst free synthesis. The ZnO nanostructures
      have been formed by evaporation of Zn (99.99%) in O2 and Ar atmosphere in single
      zone furnace under two temperature regions, region A (approximately 1173-1073 K)
      and region B (approximately 873-773 K). Through application of XRD and TEM
      techniques, it has been shown that first ZnO is formed which changes to ZnOx
      through creation of oxygen vacancies. The ZnOx acts as self-catalyst and leads to
      formation of various nanostructures. Those observed in the present investigation
      are nanotetrapods (1 D, diameter approximately 70-450 nm, length approximately 2
      4.5 approximatelym) nanorods (1 D, diameter approximately 45-95 nm, length
      approximately 2.5-4.5 microm), nanoflowers(2D, central core diameter
      approximately 90-185 nm, length of petals/nanorod approximately 1.0-3.5 microm)
      and nanoparticles (3D, size approximately 0.85-2.5 microm). These nanostructures
      have been revealed by SEM explorations. Attempts have been made to explain the
      formation of the various nanostructures in terms of the creation and distribution
      of the ZnOx, the temperature as well as oxygenation conditions.

PMID- 16430147
TI  - Atomistic simulations of J-integral in 2D graphene nanosystems.
AB  - The J-integral is investigated in discrete atomic systems using molecular
      mechanics simulations. A method of calculating J-integral in specified atomic
      domains is developed. Two cases, a semiinfinite crack in an infinite domain under
      the remote K-field deformation and a finite crack length in a finite geometry
      under the tensile and shear deformation prescribed on the boundary, are studied
      in the two-dimensional graphene sheets and the values of J-integral are obtained
      under small-strain deformation. The comparison with energy release rates in Mode
      I and Mode II based on continuum theory of linear elastic fracture mechanics show
      good agreements. Meanwhile, the nonlinear strain and stress relation of a 2D
      graphene sheet is evaluated and is fitted with a power law curve. With necessary
      modifications on the Tersoff-Brenner potential, the critical values of J-integral
      of 2D graphene systems, which denoted as Jc, are eventually obtained. The results
      are then compared with those from the relevant references.

PMID- 16430148
TI  - Nanocrystallization of ferroelectric strontium bismuth vanadium niobate in
      lithium tetraborate glasses.
AB  - Transparent glass samples in (100-3x) (Li2O-2B2O3)-x(SrO-Bi2O3-0.7Nb2O5-0.3V2O5)
      (10 < or = x < or = 60, in molar ratio) system have been fabricated via
      conventional melt-quenching technique. The as-quenched samples, of all the
      compositions under study have been confirmed to be amorphous, by X-ray powder
      diffraction (XRD) studies. Differential thermal analysis (DTA) was employed to
      confirm the glassy nature of the as-quenched glasses. Glass composites comprising
      vanadium doped strontium bismuth niobate nanocrystallites were obtained by
      controlled heat-treatment of the as-quenched glasses at 783 K for 6 h. Perovskite
      SrBi2(Nb0.7VO3)2O9-delta phase formation was found to be preceded by an
      intermediate fluorite phase which was established via XRD and transmission
      electron microscopy (TEM). The dielectric constants (epsilonr) of the as-quenched
      glasses as well as the glass nanocrystal composites decreased with increase in
      frequency (100 Hz-10 kHz) at 300 K. Interestingly, the dielectric constant of the
      glass nanocrystal composite (heat-treated at 783 K/6 h) undergoes a maximum in
      the vicinity of the crystallization temperature of the host glass (Li2B4O7)
      reaching an anomalously high value (approximately 10(6)) at 800 K. Different
      dielectric mixture formulae were employed to rationalize the dielectric
      properties of the glass nanocrystal composite. The optical transmission
      properties of these glass nanocrystal composites were found to have strong
      compositional dependence.

PMID- 16430149
TI  - Application of carbon nanomaterial as a microwave absorber.
AB  - Microwave absorption (8 GHz to 12 GHz) studies have been made with carbon
      nanomaterials for the first time. Carbon nanomaterials are synthesized by the
      pyrolysis of camphor. It is observed that film of carbon prepared under certain
      synthetic condition, can absorb microwave of either some specific wavelengths
      e.g., 9.5 GHz and 11.5 GHz or full range from 8-12 GHz to the extent of 20 dB
      depending upon their preparation condition. Carbon nanobeads seems to absorb the
      microwave in the range of 8-12 GHz.

PMID- 16430150
TI  - Complexes of carbon nanotubes with selected carotenoids.
AB  - As proven by the UV-VIS, micro-Raman spectroscopies, differential scanning
      calorimetry, beta-carotene, lycopene, retinoic acid, and retinol adsorbed on the
      surface of single-walled carbon nanotubes (SWCNT) form electron donor-acceptor
      (EDA) complexes. The rate of the adsorption of carotenoids is estimated as the
      rate of decrease in their concentration in solution followed the exponential
      curve equation. The rate of the adsorption decreased with the chain length of the
      guest capable sorption on the surface and steric effect of the terminals in the
      beta-carotene was also essential. Also, increase in the polarity of the
      functional groups expressed, for instance, in Taft sigma* substituent constants
      had its impact. The HyperChem 7 followed by Gaussian 03 computations revealed
      that the inclusion SWCNT-carotenoid complexes were more stable than corresponding
      surface complexes. In the surface complexes carotenoids acted as donors in
      respect to SWCNT whereas in the inclusion complexes they were acceptors.

PMID- 16430151
TI  - Photosynthesis of gold nanoparticles in presence of proteins.
AB  - This paper describes the photosynthesis of gold nanoparticles (GNPs) in the
      presence of bovine serum albumin (BSA). The concentration of NaAuCl4 and the
      relative ratio of NaAuCl4 to BSA are important parameters for controlling the
      size of the GNPs. We prepared GNPs having average diameters ranging from 7 to 50
      nm by illumination (Hg-Xe lamp) of phosphate-buffered solutions (pH 3.0-11.0)
      containing 1 mM NaAuCl4 and 10 microM BSA for 9 h. The size distribution of the
      GNPs synthesized at pH 7.0 is narrower relative to that of those prepared at
      other values of pH. Based on the observation that there are no GNPs formed at 25
      degrees C in the absence of either BSA or illumination, we conclude that
      photolytic reduction is the main mechanism for the formation of the GNPs and that
      BSA acts as a capping agent to stabilize the as-synthesized GNPs. In addition to
      BSA, several other proteins, such as beta-casein, conalbumin, hemoglobin, beta
      lactoglobulin, lysozyme, myoglobin, ovalbumin, pepsin, and trypsinogen play the
      same role.

PMID- 16430152
TI  - Preparation of AlFe nanoparticles by mechanical alloyed technique.
AB  - Small metallic particles (1-3 nm) have been obtained using mechanical alloying
      techniques. Analytical techniques such as scanning electron microscopy have been
      used for the morphological and chemical characterization of the AlFe alloyed
      powders. B, Ni and Ti have been explored as reinforced elements to the initial
      AlFe mixture. X-ray diffraction patterns and transmission electron microscopy
      (TEM) techniques have been employed for the structural characterization of the
      small metallic particles. Theoretical simulations based on molecular dynamics
      have been used to interpret some of the experimental structural results.
      Furthermore, theoretical simulations of HREM images based on the dynamical theory
      of electron diffraction have also been obtained and comparisons with the
      experimental results have been carried out. The complementary analyses determined
      that the produced clusters are basically AlFe alloyed nanoparticles immersed in a
      matrix and with multiple defected structures.

PMID- 16430153
TI  - Effect of titanate-based surface on hydrophilicity and interlayer spacing of
      montmorillonite clay for polymer nanocomposites.
AB  - The fundamental scientific investigations on structure-property correlation of
      organo-clay are quite valuable in understanding the interface chemistry thus to
      design and engineer the most effective polymer-clay nanocomposites systems.
      Organo alkyl-titanate derivatives have been used as reagents for the surface
      modification of pristine montmorillonite clay platelets. Such surface
      modification is validated through coordinated characterization techniques that
      include X-ray photoelectron spectroscopy (XPS), contact angle measurements, X-ray
      diffraction (XRD) and thermo gravimetric analysis (TGA). By fine-tuning the
      surface characteristics (controlling the hydrophilicity); effective
      nanodispersion in polymers by intercalation or delamination can be accomplished.
      The titanate-coupling agent increased the water contact angle of the clay from 6
      to 44 degrees denoting significant decrease in hydrophilicity. Similarly, XRD
      studies revealed the increased inter-gallery spacing from 9.8 to 12.7 A. The
      grafting of titanate modifier on to clay surface is quantified through XPS
      elemental analysis and co-related with TGA. This new surface-modification method
      provides an effective technique to convert the hydrophilic surface of the
      montmorillonite clay into organophillic for polymer-clay nanocomposites.

PMID- 16430154
TI  - Synthesis of CdS and alloyed CdMnS nanocrystals using aqueous foams.
AB  - Certain surfactant-stabilized aqueous foams provide a potentially efficient and
      simple chemical route for the synthesis of various nanomaterials with
      controllable structure, size, and shape. In the present work, a one-step process
      for the synthesis of CdS and Cd1-xMn(x)S (0 < x < 10) nanocrystals has been
      described. Aqueous CdCl2 and the aerosol-OT solutions are homogeneously mixed
      together and thereafter, nitrogen is bubbled through this solution to produce
      stable aqueous foam. After drainage of the foam, the freestanding dry foam
      consisting of cadmium cations electrostatically complexed with the anionic
      aerosol-OT molecules at the liquid-gas interface is treated with H2S vapor. The
      foam turns yellowish-orange and collapses, in the process yielding CdS
      nanoclusters of variable morphology. This morphology variation is appropriately
      attributed to growth of the CdS as well as alloyed Cd1-xMn(x)S nanoparticles in
      different regions of the foam contributing to the varying topological structure.
      Optical absorption spectra of both CdS and Cd1-xMn(x)S nanoparticles clearly show
      a well-defined exciton absorption feature around 450 nm due to quantum
      confinement effects. The interesting band edge emission characteristics of these
      AOT-capped CdS and Cd1-xMn(x)S nanoparticles produced in the foam are discussed
      with respect to their size and shape. Particular interest in the present novel
      aqueous foam approach arises due to the fact that the cubic zincblende CdS and
      alloyed Cd1-xMn(x)S nanocrystals could easily be obtained even under ambient
      experimental conditions itself.

PMID- 16430155
TI  - Incontinuous grain growth in cobalt nanocrystalline powders prepared by high
      energy mechanical milling.
AB  - Cobalt nanocrystalline powders with the average grain size of about 17 nm were
      prepared by high-energy mechanical milling. Grain growth in highly pure and
      particle-containing nanocrystalline Co powders were investigated respectively by
      a series of annealing experiments at different temperatures. The characteristics
      of incontinuous grain growth were found in both the pure and the particle
      containing nanocrystalline powders. It is proposed by the authors that the sharp
      increase in nanograin size in the transition between the low and high temperature
      regions is a result of enhanced grain growth promoted by the stored energy as a
      supplied driving force, based on which rapid grain growth occurs through a
      particular dominant mechanism of nanograin rotations in the pure nanocrystalline
      powders, and that through off-pinning of grain boundaries in the particle
      containing nanocrystalline powders.

PMID- 16430156
TI  - Development of a low density colorimetric protein array for cardiac troponin I
      detection.
AB  - This work presented a rapid, inexpensive, reliable, and flexible quantitative
      immunoassay for cardiac troponin I (cTnI). The assay was based on the concepts of
      one-step dual monoclonal antibody "sandwich" principle, the low density protein
      array, the nanogold probe, and the silver enhancement on the gold particles. The
      capture antibody (IgG1) coated supporting nitrocellulose membrane and the
      colloidal gold-labeled detection antibody (cAu-IgG2) were prepared before the
      detection. The detection procedure involved two steps, i.e., immunoreaction and
      silver amplification. The assay needs only small amounts of serum samples of
      patients, The whole detection procedure of the assay could be fulfilled within 40
      min (much faster than the routine enzyme-linked immunosorbent assay (ELISA) that
      takes usually at least 3 hours for a turnaround test). The detection results
      could be easily imaged with a simple flatbed scanner or even observed with the
      naked eye. The assay showed good specific response to cTnI with very little cross
      reactivity to the skeletal isoforms of troponin I (sTnl), cardiac troponin T
      (cTnT), and myoglobin (Mb). A cut-off value of 0.3 ng/ml was obtained from a
      reference control group (200 normal serum samples). 588 patients' serum samples
      were assayed simultaneously by routine ELISA and this colloidal gold method to
      test the validity of the method. The data were analyzed using the statistical
      package SPSS version 11.0 (SPSS Inc.) There was no significant difference between
      these two assays (P = 0.66 > 0.05). The agreement between this method (> or < 0.3
      ng/ml) and ELISA was 86%.

PMID- 16430157
TI  - Effect of surface roughness on dip-pen nanolithography.
AB  - In the present work, five gold thin films with various surface roughnesses were
      prepared by sputtering and the influence of the surface roughness of gold
      substrate on dip-pen nanolithography (DPN) was studied using 1-octadecanethiol
      (ODT) and poly(vinylidene fluoride-trifluorethylene) [P(VDFTrFE)] as inks. It was
      shown that surface roughness influences both the contrast in lateral force
      microscopy (LFM) images and the transport rate of ink. Surfaces with less
      roughness give good contrast in LFM images, while rough surfaces give poor
      contrast. The transport rate of ink increases as the roughness decreases;
      however, the extent of the influence is strongly ink-dependent.

PMID- 16430158
TI  - [An outbreak of Klebsiella pneumoniae mastitis].
AB  - A serious outbreak of mastitis caused by Klebsiella pneumoniae is described.
      Shortly after drying off, three cows died of mastitis caused by Klebsiella
      pneumoniae and five other cows became seriously ill but survived. Sawdust
      contiminated with Klebsiella pneumoniae was identified as the most likely source
      of these infections. In addition to detection of possible sources of infection,
      another important aspect of eradication is the detection of quarters infected
      with Klebsiella pneumoniae. Rigorous application of these measures led to
      resolution of the outbreak within a few months.

PMID- 16430159
TI  - [Caring father].

PMID- 16430160
TI  - [RDA advice 2005/07 'the recognized veterinarian'].

PMID- 16430161
TI  - [The new veterinary drug agreement and the new veterinary drug rules 2005: what
      does that mean for your practice?].

PMID- 16430162
TI  - [International foot and mouth disease exercise].

PMID- 16430163
TI  - [Quality and security of biological animal products].

PMID- 16430164
TI  - [Veterinarian in the House of Congress. Interview by Miel Bingen].

PMID- 16430165
TI  - [Clinical registries, fundamental to veterinary production management].

PMID- 16430166
TI  - [From farmers who have family in the United States, I hear positive results with
      'cow drenching'].

PMID- 16430167
TI  - [There is no shame in changing opinions, if it is better].

PMID- 16430168
TI  - [Practice management: also for you!].

PMID- 16430170
TI  - [Effect of pulsed Nd: YAG laser irradiation on periodontal ligament fibroblast
      cultures].
AB  - OBJECTIVE: To evaluate the effect of the pulsed Nd: YAG laser irradiation on the
      survival rate of human penodontal ligament fibroblast (PDLF) at different power
      and irradiation time settings, and to compare the morphological change of cells
      before and after irradiation. METHODS: The cells were cultured and placed into
      the 96-well tissue culture plates. Cells were divided into groups according to
      the irradiation time (10 s, 20 s, 40 s, 60 s) and the output energy (0.5 W, 1.0
      W, 1.5 W, 2.0 W, 2.5 W). After the irradiation, the cell number were counted and
      the survival rates were calculated. The correlation between the survival rate and
      irradiation time as well as power output was analyzed. RESULTS: No significant
      reduction of survival rates were found in 10 s group, as well as in 20 s group
      with 0.5 W, 1.0 W setting. The increase of the power output and increase of the
      irradiation time caused significant reduction of cell survival rate (P <0.05).
      The irradiation time was more relevant to this reduction than the power output.
      CONCLUSION: It indicates that the laser irradiation may cause damage to PDLF and
      decrease the cell survival rate. The irradiation time is more related to this
      effect than the power output.

PMID- 16430169
TI  - [Construction of recombinant plasmid pEGFP-BMP7 and its expression in rat bone
      marrow mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To construct recombinant plasmid pEGFP-BMP7 and determine its
      expression in rat bone marrow mesenchymal stem cells (MSCs) in vitro. METHODS:
      cDNA of target gene was obtained from neonatal rat kidney by RT-PCR. After
      sequencing the target gene, the cDNA was subcloned into a eukaryote plasmid pEGFP
      N1 by directed cloning and then digested with two restrictive endonucleases to
      verify the correctiveness of the recombinant plasmid pEGFP-BMP7. Rat bone marrow
      MSCs were transiently transfected with the pEGFP-BMP7 and transfection efficiency
      of the Green Fluorescent Protein (GFP) was determined. RT-PCR and
      immunocytochemical analysis were also performed to detect the expression of BMP7
      in rat MSCs. RESULTS: 1 311 bp cDNA fragment was obtained by RT-PCR and sequence
      analysis showed it matched perfectly with that of rat BMP7 gene except a single
      nucleotide change at 756 bp from T to A. Digestion of the recombinant plasmid
      showed two 1.3 kb and 4.7 kb fragments and their size were same as those of BMP7
      and pEGFP. This indicated that BMP7 cDNA was successfully subcloned into pEGFP.
      Transient transfection showed an efficiency of 33% at day 2 in rat MSCs. After
      transfection, transcription of BMP7 was detected in MSCs and expression of BMP7
      protein was also verified. CONCLUSION: Recombinant eukaryote plasmid pEGFP-BMP7
      was successfully constructed and expressed in rat bone marrow MSCs. This
      procedure may provide a unique method for stimulation of callus formation in
      distraction osteogenesis and reconstruction of craniofacial bone defects.

PMID- 16430171
TI  - [Feasibility of cationic lipid mediated nm23-h1 plasmid transfecting adnoid
      cystic carcinoma in vivo].
AB  - OBJECTIVE: To investigate the feasibility of plasmid nm23-h1 transfection on high
      metastatic potential adnoid cystic carcinoma (ACC-M) cell line mediated by
      cationic lipid. METHODS: ACC-M cell were implanted in the maxillofacial region in
      each of 40 BALB/c nude mice. After the tumor growth to 1 cm in diameter, 0.1 ml
      Lipofctamine-nm23-hl plasmid complex were injected intratumorally in 10 mice, 3
      days after the first injection, 10 mices injected for twice, 10 mice as plamid
      blank control, another 10 mice were injected 0.2 ml complex, 2, 3, 7days after
      the injection, the mice were killed and the specimen for HE and
      immunohistological chemistry study. RESULTS: nm23-h1 expression initiated in the
      tumor cells 3 days after the complex injection, 7 days later, the expression
      level increased accompanying with extracellular matrix increase, twice injection
      and multiple channel injection would gain better nm23-h1 expression than once
      injection and single-channel injection respectively. CONCLUSION: Cationic lipid
      mediated nm23-h1 plamid transfecting adnoid cystic carcinoma can gain small range
      positive expression, but the results give little prospect for further clinical
      treatment in such a manner.

PMID- 16430172
TI  - [Study of the expression of integrin alphaV beta3 in mandibular distraction
      osteogenesis].
AB  - OBJECTIVE: To investigate the expression and distribution pattern of Integrin
      alphaV beta3 (ItgalphaV beta3) in course of distraction 44 adults New Zealand
      white osteogenesis and to quest for the function of ItgalphaV beta3 in
      distraction osteogenesis (DO). METHODS: rabbits were selected and divided
      randomly into 3 groups: DO, bone fracture and normal group. There were 20, 20 and
      4 rabbits in each group separately. Animal models were established and animals
      were killed at different time points. Sections were stained by IHC method.
      Distribution and expression pattern of ItgalphaV beta3 were observed by semi
      quantitative technique, and the results were managed with statistic methods.
      RESULTS: The expression of ItgalphaV beta3 was found both in the DO and bone
      fracture groups. The positive staining was seen mainly in vascular endothelial
      cells on cytomembrane and in cytoplasm. The staining intensity of group of DO was
      higher than that of the bone fracture group. CONCLUSION: ItgalphaV beta3 plays an
      important role in promoting the process of DO.

PMID- 16430173
TI  - [Predominant aciduric microflora related to fissure caries of the first permanent
      molars].
AB  - OBJECTIVE: To investigate the aciduric bacteria in different stages of the
      fissure caries in order to determine potential roles of the microflora in the
      development of dental caries. METHODS: Plaque samples were taken from 10
      incipient carious fissures of the first permanent molars. Plaque samples were
      also collected from sound fissures of the first permanent molars in 10 other
      subjects who kept caries free over the past 2 years and from the above 10
      subjects. The predominant bacteria were isolated by using both the most probable
      method in media at pH7.0 and 5.2, and the conventional plating methods.
      Streptococcus spp. was identified by means of API 20 Strep commercial kit.
      RESULTS: S. mutans was the predominant aciduric bacteria infissures of caries
      free children and more frequently recovered at neutral pH. Whilst, S. sanguis was
      predominant at pH5.2 in sound and carious of fissures of caries-active children.
      The proportion of Gram-positive rods at pH5.2 was 82%, significantly greater than
      that of 61% at pH7.0. CONCLUSION: The ecology of plaque is complex and the
      composition of microflora at each stage of caries could be different. The
      composition of bacteria was consistent with the changes of local pH in the
      plaque.

PMID- 16430174
TI  - [Influences of applying force during the different stages of estrous cycle on
      orthodontic tooth movement of rats].
AB  - OBJECTIVE: To explore the effects of applying force during the different stages
      of estrous cycle on orthodontic tooth movement of rats, so as to offer an
      experimental princinple for women's orthodontic treatment. METHODS: 80 female 3
      month-old Wistar rats, which had a stable and five-day estrous cycle, were used.
      They were randomly divided into control groups and loading-force groups. Each
      group was divided again into 4 sub-groups according to the different stages of
      the estrous cycle. The loading-force groups received repeated intermittent
      orthodontic force for four times seperately during the same stage of the estrous
      cycle. The distance between upper incisor and the first molar on the left was
      measured. The data were analyzed by One-way ANOVA, S-N-K. RESULTS: There were
      significant variations in the amount of tooth movement among the groups which
      received the mechanical force during the different stages of the estrous cycle (P
      <0.01). There were significant variations in the amount of tooth movement between
      the groups received force during pre-estrus and estrus (P <0.05). There were not
      significant variations between the groups received force during metestrus and
      diestrus (P > 0.05). The largest amount of tooth movement was in estrus group and
      smallest in pre-estrus one. CONCLUSION: The effect of tooth movement depended on
      which stage of estrous cycle was chosen to be the time of applying orthodontic
      force.

PMID- 16430175
TI  - [Reliability of an improved measurement system used in three-dimensional
      reconstruction of stomatognathic system by cutting and scanning layer-by-layer].
AB  - OBJECTIVE: To reconstruct 3D shape of edentulous jaw by using improved
      measurement system and to analyze the precision of this method. METHODS: Standard
      edentulous jaw models were measured with a improved measurement system by cutting
      and scanning layer-by-layer, and the 3D shape of the models was reconstructed by
      image processing with specialty software. Ten cubic plaster modes were
      reconstructed by the same way, data of every border before and after
      reconstruction were measured and analyzed. RESULTS: Data of edentulous jaw models
      were obtained. The errors in ten cubic before and after reconstruction were not
      significantly different (P > 0.05), data measured in horizontal plane were not
      significantly different (P > 0.05), and data measured in altitude direction were
      significantly different (P < 0.01), data measured after reconstruction were less
      than before, the error was (0.09 +/- 0.08) mm. CONCLUSION: The improved cutting
      and scanning measurement system can be fit for the 3D reconstruction of
      stomatognathic system with high precision.

PMID- 16430176
TI  - [Stress distribution analysis of the surface of condyle during simulated fracture
      healing of the neck of condyle by miniplate osteosynthesis].
AB  - OBJECTIVE: To find the reasons why patients always have temporomandibular
      disorders (TMD) after condylar fracture by analyzing the stress distribution
      change of the condylar surface whose subcondylar fracture ware fixed by miniplate
      during the whole healing process. METHODS: Analyzing the stress distribution
      change of the condylar surface whose subcondylar fracture were fixed by miniplate
      during the whole healing process by three-dimension finite element method (3D
      FEM). RESULTS: During the whole healing process of the fracture, the miniplate
      osteosynthesis was helpful to the biomechanics environment rehabilitation of the
      condylar local, but it still had difference with normal after fixing 12 weeks
      long. CONCLUSION: The difference of stress distribution of condylar surface that
      fractured and fixed by miniplate with normal may be part of the reason of TMD
      after the subcondylar fracture miniplate osteosynthesis.

PMID- 16430177
TI  - [Analysis of psychological condition of parents with cleft lip and/or palate
      children].
AB  - OBJECTIVE: To evaluate the psychological situations of cleft lip and/or palate
      children's parents, to discuss the relationship between psychological situations
      and cleft types, and to provide clinical treatment to improve the psychological
      situations of these parents. METHODS: 100 parents whose children were proceeded
      the primary surgery treatment were selected as the study group, and other 34
      parents whose children were normal as the control group. All parents were
      inquired and tested by the life event scale (LES) and self-rating anxiety scale
      (SAS). RESULTS: The LES total scores of the cleft lip and/or palate patients'
      parents were significantly high compared with the normal (P < 0.05). The SAS
      total scores of the cleft lip and/or palate patients' parents had no significant
      difference with the control group (P > 0.05). The scores of cleft lip and/or
      palate patients' parents were the highest and the scores of cleft palate
      patients' parents were the lowest. CONCLUSION: Most of the cleft lip and/or
      palate patients' parents were disturbed by a negative psychological situation.
      Some kind of negative psychological situation may manifest some body symptoms.
      Meanwhile,the three subgroups' data had the significant difference, which
      indicated that parents may much more care about the appearance abnormality.

PMID- 16430178
TI  - [Primary study of pharyngeal flap surgery in congenital velopharyngeal
      insufficiency].
AB  - OBJECTIVE: To study effective operation method of congenital velopharyngeal
      insufficiency by reviewing clinical data of 29 patients with pharyngoplasties.
      METHODS: 29 patients (9 male and 20 female, ranged from 4 to 25 years old, mean
      age was 13.5) with congenital velopharyngeal insufficiency were available for
      this study. All cases received Chinese speech intelligibility test and blowing
      test before and after the pharyngeal flap surgery. RESULTS: Chinese speech
      intelligibility of 29 cases who underwent pharyngoplasties was improved from
      33.86% to 43.13%, and the blowing time was increased from 4.60 to 17.72 seconds,
      the degree of abnormal speech was reduced. CONCLUSION: The pharyngeal flap
      surgery is an effective method for congenital velopharyngeal insufficiency, which
      reduces hypernasality and increases oral pressure, improves the velopharyngeal
      function.

PMID- 16430179
TI  - [Association of estrogen receptor gene polymorphisms and primary trigeminal
      neuralgia].
AB  - OBJECTIVE: To investigate the association of estrogen receptor (ER) gene
      polymorphism and primary trigeminal neuralgia. METHODS: By polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP), ER gene
      polymorphism was analyzed in 20 trigeminal neuralgia (TR) patients and 20 control
      individuals, and the distribution of ER genotype was compared in TR group and
      control group. RESULTS: There was no significant difference in frequencies of
      allele and genotype in XbaI or PvuII polymorphism or XbaI with PvuII
      polymorphisms together between TR group and control group (P > 0.05). The
      genotypic distribution of Xx or PpXx in TR group was higher than control group,
      and it was contary to xx, ppxx or Ppxx in TR group and control group. CONCLUSION:
      XbaI or PvuII polymorphism may be related to TR. Women with PpXx genotype may be
      a dangerous factor to primary trigeminal neuralgia.

PMID- 16430180
TI  - [Relationship between periodontal disease and rheumatoid arthritis].
AB  - OBJECTIVE: To study a population of rheumatoid arthritis patients and determine
      the extent of periodontal disease in these patients, in order to investigate the
      relationship between periodontal disease and rheumatoid arthritis. METHODS: The
      experimental group was composed of 70 patients with rheumatoid arthritis and the
      control group consisted of 70 age- and gender-matched individuals without
      rheumatoid arthritis. The relationship between periodontal status in rheumatoid
      arthritis and control groups as well as the relationship between periodontal
      status and rheumatological findings in patients were analyzed. RESULTS: The
      percentage of periodontal disease was statistically significant between
      experimental and control group (P < 0.01). The difference of average number of
      missing teeth and bleeding on probing in the experimental group and control group
      were not statistically significant (P >0.05). There were more number of
      periodontal disease index 5 or 6 in experimental group than in control group ( P
      < 0.05). Rheumatoid arthritis patients with moderate to severe bone loss had
      deeper degree of morning stiffness, erythrocyte sedimentation rate levels and
      serum C-reactive protein levels than patients with no or mild bone loss.
      CONCLUSION: Individuals with rheumatoid arthritis are more likely to experience
      periodontal disease compares to healthy subjects. They are also very likely to
      suffer from moderate to severe periodontitis.

PMID- 16430181
TI  - [Study of dental caries prevalence in children of Yinchuan in China].
AB  - OBJECTIVE: To assess the dental caries prevalence of children in Yinchuan.
      METHODS: The 3-, 5-, 12-, 15-year-old children were chosed from nursery, primary
      and middle schools of Yinchuan in 1990, 1996 and 2001. The survey was carried out
      by five senior dentists from stomatologic hospital of Yinchuan according WHO
      criteria. DMFT, DMFS and the ratio of tooth filled were counted. RESULTS: From
      1990 to 2001, the prevalence of dental caries of 3-, 5-, 12-year-old children was
      degression (P < 0.01). But the prevalence of dental caries of 15-year-old
      children had no obvious change. The dental caries of small proportion of children
      were serious. The ratio of tooth filling was low. CONCLUSION: With the
      development of oral health education, the prevalence of dental caries of 3-, 5-,
      12-year-old children in Yinchuan is descend. But the diagnosis, prevention and
      treatment should be strengthened, and the ratio of tooth filling should be
      increased.

PMID- 16430182
TI  - [Carotid body tumor: a retrospective study of 26 consecutive cases].
AB  - OBJECTIVE: To study the clinical features, diagnoses and operative intervention
      of carotid body tumors. METHODS: The medical records of 26 patients with carotid
      body paragangliomas between 1993 and 2004 were retrospectively reviewed. RESULTS:
      Two of twenty-six patients had bilateral tumors. One patient had malignant tumors
      with cervical lymph nodes metastases. Twenty-one patients were evaluated with a
      preoperative angiography. No preoperative embolization was performed. Eleven
      patients underwent ultrasonography, nine had CT scan of the neck, five had
      magnetic resonance imaging. Twenty-six patients were all operated. Vascular
      reconstruction was performed in five cases. The ligation of carotid artery was
      carried out in four cases and another patient had vagus nerve resection. No death
      and recurrence occurred in all cases. CONCLUSION: Angiography and ultrasonography
      are valuable in the diagnosis of carotid body tumor. Surgical removal should be
      made early to avoid the possibility of eventual metastasis and progressive local
      invasion. The pattern of operation should be chosed according to the relation of
      tumor and carotid.

PMID- 16430183
TI  - [Investigation on border mandibular movement of adolescent with angle III
      malocclusion in initial stage of permanent dentition].
AB  - OBJECTIVE: To investigate characteristics of the border mandibular movement of
      the adolescent with Angle III malocclusion and to find the correlations between
      craniofacial morphology and border mandibular movement function. METHODS: The
      subjects consisted of 21 adolescent patients with Angle III malocclusion in the
      initial stage of permanent dentition (mean age 12.3 years). 20 adolescents with
      individual normal occlusion served as control (mean age 12.8 years). The border
      mandibular movement of all cases in the two groups were traced and recorded by K6
      1 Evaluation System and standardized lateral cephalograms were taken. RESULTS:
      The results revealed no significant difference in the maximal movement range
      between two groups, but indicated a positive association between the maximum jaw
      opening and both the mandible length (Go-Gn) and the L1-MP. The distance from ICP
      to maximal opening (D) was positively correlated with facial height and the L1
      MP. While to adolescents with individual normal occlusion, the wider the maximal
      jaw opening was, the bigger the posterior facial height and the cephalometric
      values of mandibular ramus. The distance D positively correlated with the
      anterior lower facial height. CONCLUSION: Angle III malocclusion had its
      characteristics in the tracing and had a specific relationship with the
      craniofacial morphology.

PMID- 16430184
TI  - [Use of relative energy in low frequency area to describe the severity of
      hypernasality in cleft palate patients].
AB  - OBJECTIVE: To find an objective index to describe the severity of hypernasality
      in cleft palate patients through speech spectroanalysis. METHODS: 60 audio
      records of cleft palate patients were analyzed by spectroanalysis, the relative
      energy in low frequency area (REL) was calculated in the LPC spectrogram. One
      experienced speech therapist and two nonprofessionals made perceptual judgments
      of the same records. Spearman correlation analysis was conducted to test if the 3
      groups of data have significant correlations. RESULTS: REL had significant
      correlation with professional judgments (correlation coefficient was 0.272, P <
      0.05) and nonprofessional judgments (correlation coefficient was 0.274, P <
      0.05). CONCLUSION: REL can be used as one objective reference in the judgment of
      the severity of hypernasality.

PMID- 16430185
TI  - [Clinical study of complete dentures supported by two endosteal magnetic
      attachment implants].
AB  - OBJECTIVE: To evaluate treatment outcomes of mandibular complete denture
      supported by two endosteal magnetic-attachment implants in edentulous patients
      with severe mandibular alveolar ridge absorption. METHODS: Eight edentulous
      patients with severe mandibular alveolar ridge absorption were chosen. Each of
      them was treated with a complete denture supported by two CDIC implants. The
      implants were inserted at the areas of two the first premolars respectively.
      After five months, two magnets were adhered to the inside of the complete
      dentures. Retention, masticatory efficiency and maximal masticatory force were
      measured before and after the magnets were adhered and six months later. RESULTS:
      Statistical analysis revealed that retention, masticatory efficiency and maximal
      masticatory force were all increased after the magnets were adhered (P < 0.01)
      and six months later (P < 0.01). CONCLUSION: Retention, maximal masticatory force
      and masticatory efficiency were significantly increased after the endosteal
      magnetic attachment implants were applied. It is concluded that mandibular
      complete denture supported by two endosteal magnetic attachment implants is an
      effective method for severe alveolar ridge absorption cases.

PMID- 16430186
TI  - [Immortalized human odontoblast-like cell line expressed dentin extracellular
      matrix in vitro].
AB  - OBJECTIVE: To determine whether dentin matrix proteins were expressed by the
      human odontoblast-like cell line hTERT-hOd-1 in vitro. METHODS: Collagen type I,
      bone sialoprotein (BSP), dentin matrix protein 1 (DMP1) and the marker for
      odontoblast, dentin sialophosphoprotein (DSPP) and dentin sialoprotein (DSP) were
      detected in these cells by immunohistochemistry, RT-PCR and in situ
      hybridization. During being cultured in mineralizing medium for 5 weeks, the
      secretion of OC and activity of ALP were measured once a week. RESULTS: DSPP,
      DMP1, BSP and collagen type I were expressed in hTERT-hOd-1 either at mRNA or
      protein level. Under the induction of mineralizing medium, the cells showed
      higher activity of ALP and increased secretion of OC. CONCLUSION: hTERT-hOd-1
      expressed dentin extracellular matrix in vitro, which means the cell line has the
      potential of mineralization.

PMID- 16430187
TI  - [Antibacterial effect of nHA-PA66 in vitro].
AB  - OBJECTIVE: To evaluate the antibacterial activity of nHA-PA66 on the predominant
      bacteria of infected root canal in vitro. METHODS: Agar diffusion method was the
      testing method. Porphyromonas gingivalis (P. gingivalis), Fusobacteria nucleatum
      (F. nucleatum) and Prevotalla intermedius (P. intermedius) were the tested
      bacteria. The powder and polymerized film of nHA-PA66 were the test mateials
      while the CCQ and filter paper as the control. RESULTS: nHA-PA66's powder showed
      good antebacterial effect on the P. gingivalis and P. intermedius, its film was
      weaker. Both of them had no effect on F. nucleatum. CONCLUSION: nHA-PA66's
      antibacterial effect was not ideal, for better clinical results, some additives
      can be included.

PMID- 16430188
TI  - [Construction of a virulence-related gene library of Streptococcus mutans by
      suppression subtractive hybridization].
AB  - OBJECTIVE: To construct a suppression subtractive library of virulence-related
      genes from c serotype Streptococcus mutans (S. mutans), and lay foundations for
      screening the virulent genes. METHODS: After being isolated from virulent and
      avirulent strain of S. mutans respectively, the intact and high-pure genomic DNA
      was digested with three appropriate four-base-cutting restriction endonueleases
      to produce fragments of optimal length. The digested DNA of the virulent strain
      ligated with adaptor was used as tester DNA, and that of the avirulent strain as
      driver DNA. Then the suppression subtractive hybridization was carried out, and
      the efficiency of ligation and subtraction detected respectively. The subtracted
      fragments were inserted into vector pCR2. 1 using T/A cloning kit, and
      transformed into E. coli TOP10F' competent cells. Those white colonies were
      selected to construct the suppression subtractive library. RESULTS: Alu I chosen
      from three restriction endonucleases was verified to be suitable for preparing
      restriction fragments from S. mutans genomic DNA. Through electrophoresis of Alu
      I -digested DNA, a smear ranged from 0.1 to 2.0 kb was observed. The ligation
      efficiency of tester DNA with adaptor was at least higher than 25 percent. The
      subtraction efficiency of suppression subtractive hybridization confirmed the
      success in enrichment of differential genes between virulent and avirulent strain
      of S. mutans. In the subtracted group, the appearance time of the 23S rRNA gene
      both in tester and driver DNA was later than that in the unsubtracted group by
      six cycles. It suggested that suppression subtractive hybridization happened
      indeed. After the subtracted fragments were cloned, 96 colonies were picked up
      for constructing the suppression subtractive library of virulence-related genes
      of S. mutans. CONCLUSION: Suppression subtractive hybridization allows rapid and
      easy construction of virulence-related gene library of S. mutans.

PMID- 16430189
TI  - [Preparation of enamel matrix proteins controlled release microspheres and their
      biological effects on the proliferation and differentiation of human periodontal
      ligament cells in vitro].
AB  - OBJECTIVE: To prepare enamel matrix proteins (EMPs) loaded dextran-based hydrogel
      microspheres (EMPs-dex-MPs), and to evaluate their EMPs controlled release
      property and their biological effects on the proliferation and differentiation of
      human periodontal ligament cells (PDLCs) in vitro. METHODS: Using dimethylbenzene
      as the oil phase, EMPs-dex-MPs were achieved by emulsion-chemical crosslinking
      technique. The process of the recombination preparation was optimized by
      orthogonal factorization method. The configuration and size of EMPs-dex-MPs were
      determined by scanning electron microscope. The EMPs loading content and
      encapsulation rate of EMPs-dex-MPs, and their biodegradation characteristic were
      studied by routine analysis methods. Dynamic dialysis method was used to
      determine the release characteristic of EMPs-dex-MPs in vitro and its influencing
      factors. The proliferation of cultured PDLCs was measured by MTF method and the
      differentiation of PDLCs was measured by their alkaline phosphatase (ALP)
      activities. RESULTS: The results showed that EMPs-dex-MPs were homogenous and
      stable with the average diameter 25 microm, and the EMPs loading content was
      (32.8 +/- 1.2)%, the encapsulation rate was (78.9 +/- 1.0)%. Under 9%
      physiological saline solution contained a very thimbleful quantity of dextranase
      EMPs-dex-MPs could be biodegraded completely during about 40 days. The in vitro
      experiments showed that about 80% of EMPs could be released out in 20 days. Using
      EMPs-dex-MPs could enhance the proliferation responses and ALP activities of
      PDLCs more than 12 days. CONCLUSION: As a new sustained release system of growth
      factors, the dex-MPs is stable, workable and biodegradable. EMPs-dex-MPs, whose
      drug release can be controlled by preparation technique, may be more effective in
      promoting periodontal tissue regeneration.

PMID- 16430190
TI  - [Construction of the recombinant adenovirus vector expressing human CD40 ligand
      gene].
AB  - OBJECTIVE: To construct a recombinant adenovirus vector expressing hCD40L gene
      and explore it in the use of anti-tumor gene therapy. METHODS: 1,900 bp gene
      fragment was obtained form plasmid pORF-hCD40L by Xho I/Swa I cutting and then
      cloned directionally into the pShuttle plasmid, finally, the resultant plasmid
      was digested by restriction endonnuclease PmeI and subsequently cotransformtion
      into BJ5183 cells with the adenoviral backbone pAdEasy-1 to obtain the homologous
      recombinant and then the recombinant was packaged in the 293 cells. Some methods
      such as PCR and endonulease digestion were employed to identify the recombinant
      adenovirus. RESULTS: The evidences of endonulease digestion and PCR analysis
      confirmed that recombinant hCD40L gene was correctly inserted into adenovirus
      vector. CONCLUSION: The adenoviral vector which expressed hCD40L gene was
      constructed. It provides an experimental basis for studies on it expression in
      the mammalian cells and in tumor gene therapy.

PMID- 16430191
TI  - [Adhesion to buccal epithelial cells of Candida albicans isolates from oral
      lichen planus].
AB  - OBJECTIVE: To investigate the adhesion to buccal epithelial cells of Candida
      albicans isolates from erosive oral lichen planus (OLP) and nonerosive OLP, and
      its role in the development of OLP. METHODS: A total of 112 isolates, comprising
      healthy control (26), erosive OLP (62) and nonerosive OLP (24), were screened for
      the adhesion by using buccal epithelial cell (BEC) assay. RESULTS: The adhesion
      to buccal epithelial cells of the isolates from erosive OLP group was stronger
      than that of those from healthy control. CONCLUSION: Candida albicans, some
      isolates with a special virulence attribute may contribute to the occurrence and
      progression of erosive OLP.

PMID- 16430192
TI  - Neuraminidase inhibitor susceptibility network position statement: antiviral
      resistance in influenza A/H5N1 viruses.
AB  - The emerging epidemic of H5N1 avian influenza virus with spillover into the human
      population in Asia has provoked intense concern globally about the potential of
      these particularly pathogenic viruses to evolve with the capacity for human-to
      human transmission with a consequent pandemic. The availability of antiviral
      drugs with activity against influenza A viruses and the recognition of drug
      resistant variants to these drugs prompted the following report by a select group
      of the global experts--members of the Neuraminidase Inhibitor Susceptibility
      Network--on the best use of the available drugs, both for prophylaxis and
      treatment. The editors of Antiviral Therapy are pleased to be able to provide
      this document in an expeditious manner.

PMID- 16430193
TI  - Role of the inhibitory quotient in HIV therapy.
AB  - A systemic review is presented of all studies that have evaluated the inhibitory
      quotient (IQ). The IQ is defined as the ratio between (trough) drug concentration
      and level of drug resistance of the HIV isolate. From the studies presented, it
      can be concluded that for protease inhibitors (PIs) and efavirenz, the phenotypic
      IQ is associated with virological response. The genotypic IQ (GIQ) for PIs was
      also demonstrated to be associated with virological response. An intrinsic
      limitation of the GIQ is that it is only applicable for PIs, of which resistance
      is based on the cumulative effect of mutations. As the IQ can be modified by
      adjustment of the drug dosage, it may be of clinical value. Its application in
      patient care should therefore be further investigated.

PMID- 16430194
TI  - Heptad-repeat-2 mutations enhance the stability of the enfuvirtide-resistant HIV
      1 gp41 hairpin structure.
AB  - Enfuvirtide (T20) is a peptide-based fusion inhibitor derived from the heptad
      repeat 2 (HR2) region of HIV-1 glycoprotein 41 (gp41). The inhibitor binds to the
      gp41 heptad repeat 1 (HR1) region, thereby blocking viral HR1/HR2 association.
      Mutations in HR1 have been reported to cause enfuvirtide resistance and reduce
      viral fitness. In this study, we first showed that scores obtained by a residue
      specific all-atom probability discriminatory function (RAPDF) may be used as a
      reliable predictor of structural stability of gp41 mutants by comparing it to
      experimentally determined melting temperatures, and as a reliable indicator of
      enfuvirtide resistance by comparing it to experimentally determined fusion
      inhibition and viral fitness levels. We then generated an initial set of 28
      theoretical structures of the HR1/HR2 hairpin complex where each structure
      consists of one mutation on HR1 known to cause enfuvirtide resistance and a wild
      type amino acid at the corresponding HR2 residue. Mutations were then introduced
      in the corresponding HR2 residue of each structure where the wild-type amino acid
      was changed to each of the other nineteen amino acids. The enfuvirtide-resistant
      HR1 mutants with compensatory mutations at the corresponding HR2 residues had
      better RAPDF scores than those HR1 mutants with wild-type HR2. This indicates
      that mutations in HR2 improve structural stability of the HR1/HR2 hairpin complex
      and may lead to enhanced enfuvirtide resistance when present with resistant HR1
      mutations. Modification of the amino acid side chains that contribute to
      enfuvirtide resistance using the RAPDF scores as a guide may help design of a
      second generation of fusion inhibitors against the enfuvirtide-resistant strains.

PMID- 16430195
TI  - Efficacy and tolerability of the oral neuraminidase inhibitor peramivir in
      experimental human influenza: randomized, controlled trials for prophylaxis and
      treatment.
AB  - OBJECTIVE: Oseltamivir is the only oral neuraminidase inhibitor currently
      available; we determined the tolerability and antiviral efficacy of oral
      peramivir for treatment and prophylaxis of experimental human influenza A and B.
      PARTICIPANTS: 288 susceptible, healthy volunteers (ages 18-45) were inoculated
      intranasally with A/Texas/36/ 91/H1N1 or B/Yamagata/16/88 virus in four
      randomized, double-blind, placebo-controlled trials. INTERVENTIONS: For treatment
      dosing was initiated at 24 h after inoculation with peramivir doses ranging from
      100-800 mg/day for 5 days. For prophylaxis dosing was initiated 24 h before
      inoculation and continued for 4 days with peramivir doses ranging from 50-800
      mg/day. OUTCOMES: The primary outcome measure for treatment was quantitative
      viral detection defined by the area under the curve (AUC) for nasal wash viral
      titres. For prophylaxis the primary outcome measure was the incidence of virus
      recovery. RESULTS: In influenza A treatment, peramivir 400 mg q24h and 200mg
      q12h, but not lower doses, resulted in significant reductions in viral titre AUC.
      In influenza B treatment, both 400 and 800/400 mg once daily dose groups reduced
      AUC values. In influenza A prophylaxis, the percentage of individuals with nasal
      viral shedding did not differ significantly in the placebo (58%), 50 mg (61%),
      200 mg (37%) and 400 mg (31%) dose groups. In influenza B prophylaxis, shedding
      frequencies were similar in placebo (55%), 200 mg (41%), 400 mg (35%) and 800 mg
      (47%) dose groups. The drug was well tolerated in all four studies, with nausea
      and headache being the most common side effects. No drug-resistant variants were
      detected. CONCLUSION: Early treatment with peramivir was associated with
      significant antiviral effects in experimentally induced influenza in humans.
      Prophylaxis did not significantly reduce viral shedding. The relatively low blood
      peramivir concentrations observed may explain the lack of more robust antiviral
      effects, and parenteral dosing should be studied.

PMID- 16430196
TI  - Efficacy and safety of indinavir/ritonavir 400/100 mg twice daily plus two
      nucleoside analogues in treatment-naive HIV-1-infected patients with CD4+ T-cell
      counts <200 cells/mm3: 96-week outcomes.
AB  - OBJECTIVE: To evaluate the efficacy and safety of indinavir/ritonavir 400/100 mg
      plus stavudine and lamivudine twice daily in antiretroviral-therapy-naive Thai
      HIV-1-infected patients. METHODS: This was an open-label, non-randomized single
      arm study. Antiretroviral-naive patients (n=80) with CD4+ cell count < 200 x
      10(6)/l were started on stavudine and lamivudine plus indinavir/ritonavir 400/100
      mg twice daily. CD4+ cell count and HIV RNA were determined at week 0, 12, 24, 48
      and 96. HIV RNA was measured to a level of 50 copies/ml by RT-PCR assay. Primary
      analysis was statistically performed as intent to treat. The primary endpoint was
      the percentage of patients with plasma HIV RNA below 50 copies/ml at week 96.
      RESULT: Eighty antiretroviral-therapy-naive patients with median CD4+ cell count
      19 x 10(6)/l (range: 2 - 197 x 10(6)/l) and median baseline plasma HIV RNA of
      174,000 copies/ml (range 16,800-750,000 copies/ml) were enrolled. In the intent
      to-treat analysis at week 96, the proportion of patients with HIV RNA of <50
      copies/ml was 68.8% (95% confidence interval [CI]: 68.3-69.3), whereas it was
      88.7% (95% CI: 88.1-89.3) in the on-treatment analysis at week 96. The regimen
      was well tolerated. Hyperglycaemia, hypercholesterolaemia and
      hypertriglyceridaemia were found in 8.3, 33.3 and 37.0% of the patients,
      respectively. Treatment was stopped in 18 patients; two from intolerance, two
      switched therapy, four as a result of serious adverse event-related death, and
      ten were lost to follow-up. CONCLUSION: Our study demonstrates that
      indinavir/ritonavir 400/100 mg plus stavudine and lamivudine twice daily, the
      least expensive boosted protease inhibitor, appears to be effective and safe up
      to 96 weeks despite high baseline viraemia and low CD4+ cell count in
      antiretroviral-naive patients.

PMID- 16430198
TI  - Arterial stiffness in HIV-infected patients receiving highly active
      antiretroviral therapy.
AB  - HIV-infected patients receiving highly active antiretroviral therapy (HAART) are
      at increased risk of cardiovascular events. Reported non-invasive techniques for
      assessment of blood pressure in this population have been limited to
      sphygmomanometry. The present crosssectional study investigated the impact of
      antiretroviral therapy and the HAART-associated lipodystrophy on aortic blood
      pressure conditions and arterial stiffness in HAART-treated lipodystrophic (n=42)
      and non-lipodystrophic (n=17) patients. Pulse wave analysis, novel to this
      population, was used to evaluate measures of arterial stiffness, including the
      heart rate corrected augmentation index, AgI(HR). Results indicated no
      significant difference between the study groups in peripheral or aortic blood
      pressure and AgI(HR). Significant correlates of AgI(HR) included age (P = 0.003),
      duration of antiretroviral therapy (P = 0.020), lamivudine therapy (P = 0.015)
      and ritonavir therapy (P = 0.016) as well as cumulative exposure to protease
      inhibitors (P = 0.030). Time since HIV diagnosis, severity of immunodeficiency or
      presence of HAART-associated lipodystrophy bore no relationship to AgI(HR). In
      multivariate analysis, duration of antiretroviral therapy (P = 0.046), cumulative
      exposure to nucleoside reverse transcriptase inhibitors (P = 0.032) and to
      protease inhibitors (P = 0.011) were identified as independent factors predicting
      AgI(HR). Prolonged antiretroviral treatment, thus, delineates as a risk factor
      for systemic arterial stiffness and the associated cardiovascular mortality.

PMID- 16430197
TI  - Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing
      protease inhibitors with efavirenz in HIV-infected children.
AB  - OBJECTIVE: To assess the impact on immunological, virological and metabolic
      parameters of replacing protease inhibitors (PIs) with efavirenz and replacing
      stavudine with tenofovir in HIV-infected children. METHODS: A 48-week prospective
      evaluation of 28 HIV-infected children, with stable undetectable HIV-1 loads, who
      were taking highly active antiretroviral therapy (HAART) containing lamivudine,
      stavudine and a PI. Individuals were randomized to switch PI to efavirenz and
      stavudine to tenofovir at baseline (Group 1) or at week 24 (Group 2). Patient
      assessment included: clinical evaluation, viral load, CD4+ T-cell count, fasting
      blood levels and urine samples. RESULTS: All individuals maintained HIV RNA <50
      copies/ml and unchanged CD4+ T-cell count through week 48. In Group 1
      individuals, a significant decrease in cholesterol (P < 0.05), cholesterol:high
      density lipoprotein (HDL) ratio (P < 0.01) and triglycerides (P < 0.05) was
      observed 24 and 48 weeks after the switch of HAART. The percentage of Group 1
      children with increased cholesterol and triglycerides markedly decreased over the
      study period (from 43% to 0% and from 36% to 7%, respectively). In Group 2
      individuals, unchanged lipids in the 24 weeks prior to the switch of HAART and a
      significant improvement on cholesterol (P < 0.05), cholesterol:HDL ratio (P <
      0.01) and triglycerides (P < 0.05) were observed 24 weeks after the switch of
      HAART. The percentage of Group 2 children with increased cholesterol and
      triglycerides markedly decreased 24 weeks after the switch of HAART (from 46% to
      7% and from 54% to 0%, respectively). Proteinuria and glucosuria were not
      detected in any individual. The mean values of serum creatinine, serum
      phosphorus, serum bicarbonate, estimated glomerular filtration rate, urinary
      microalbumin/creatinine, alpha-1-microglobulin/creatinine ratio and maximal
      tubular phosphate reabsorption remained unchanged in both groups. CONCLUSIONS: In
      HIV-infected children, switching PI to efavirenz and stavudine to tenofovir is
      virologically and immunologically safe, is not associated with renal impairment
      and provides a significant improvement in lipid profile.

PMID- 16430199
TI  - Nevirapine plasma concentrations and concomitant use of rifampin in patients
      coinfected with HIV-1 and tuberculosis.
AB  - OBJECTIVES: In countries with high numbers of HIV/tuberculosis coinfection
      nevirapine and rifampin are used extensively. However, limited data are available
      about whether or not nevirapine and rifampin can be safely coadministered without
      the plasma concentration of nevirapine falling below therapeutic levels. METHODS:
      Blood samples for determination of nevirapine plasma concentrations were
      collected from patients using nevirapine 200 mg twice daily with or without
      concomitant rifampin. Bivariate and multivariate linear regression models were
      used to investigate factors possibly related to nevirapine concentrations.
      RESULTS: We received 74 blood samples from patients using nevirapine plus
      rifampin, and collected blood samples from an equal number of controls using
      nevirapine only. Groups were similar for age, gender, weight, height and body
      mass index (BMI). In the rifampin group the mean nevirapine concentration was
      5.47 +/- 2.66 mg/l, whereas in the control group the mean nevirapine
      concentration was 8.72 +/- 3.98 mg/l. In the rifampin group seven nevirapine
      trough concentrations were low (< 3.1 mg/l), while in the control group two
      patients had low nevirapine trough concentrations (P = 0.164). In the
      multivariate linear regression analysis, corrected for time after drug intake,
      the use of rifampin was significantly (P < 0.001) associated with lower
      nevirapine plasma concentrations, whereas higher BMI reached borderline
      significance (P = 0.065). CONCLUSION: Although nevirapine plasma concentrations
      were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of
      these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results
      suggest that from a pharmacological point of view the majority of Thai coinfected
      patients, who have low BMIs, reach nevirapine plasma concentrations that are
      adequate for treatment of HIV. However this can only be undertaken if nevirapine
      plasma concentration monitoring is available and can be closely followed.

PMID- 16430200
TI  - In vivo effects of highly active antiretroviral therapies containing the protease
      inhibitor nelfinavir on mitochondrially driven apoptosis.
AB  - BACKGROUND: In vitro studies have reported controversial effects of protease
      inhibitors (PIs) on mitochondrially driven apoptosis. Additionally, since PIs in
      the clinical setting are almost always given in combination with nucleoside
      analogues, which may have negative effects on mitochondrial DNA (mtDNA), the
      impact of PI-containing highly active antiretroviral therapy (HAART) on apoptosis
      and mtDNA content is unclear. PATIENTS AND METHODS: A cross-sectional study was
      performed including 20 HIV-negative (HIV-) patients, 16 HIV-positive,
      antiretroviral-naive (HIV+) patients and 17 HIV-positive patients receiving the
      PI nelfinavir (NFV) plus zidovudine and lamivudine (AZT+3TC) or didanosine and
      stavudine (ddl+d4T)--collectively known as HIV+PI--as first-line antiretroviral
      treatment for at least 12 months. Peripheral blood mononuclear cells (PBMCs) were
      isolated. BCL2 expression (anti-apoptotic) and the levels of the cleaved, active
      form of caspase-9 (pro-apoptotic) were determined by western blot. An index of
      mitochondrially driven apoptotic activation was estimated calculating the ratio
      caspase-9:BCL2. Mitochorldrial DNA content was measured by real-time PCR.
      RESULTS: BCL2 expression was lower in HIV+ than in HIV-patients (P < 0.01),
      whereas levels of caspase-9 were higher (P = 0.001). The caspase-9:BCL2 ratio was
      significantly increased in HIV+ compared with HIV-individuals (P < 0.001).
      Mitochondrial DNA content was also decreased in HIV+ compared with HIV-patients
      (P < 0.001). The HIV+PI group exhibited a trend to normalization for BCL2
      expression and caspase-9 compared with the HIV+ group, whereas the caspase-9:BCL2
      ratio significantly improved (decreased, P < 0.05 compared with HIV+ group). The
      mtDNA content in the HIV+PI group was similar to that of the HIV+ group, although
      the results of mtDNA content differed depending on whether NFV was combined with
      AZT+3TC (preserved) or with ddl+d4T (depleted). Conversely, no differences were
      found in apoptotic markers between the two subgroups of HIV+PI. CONCLUSIONS: NFV
      based PI-containing HAART regimens may exert some beneficial effects
      counteracting the increased mitochondrially driven apoptosis present in HIV
      infected people.

PMID- 16430201
TI  - The liver in HIV in Africa.
AB  - As access to antiretroviral therapy improves across the African continent, liver
      disease is emerging as an important cause of morbidity and mortality among HIV
      infected individuals. Although coinfection with hepatitis B virus (HBV) and
      hepatitis C virus (HCV), along with highly active antiretroviral therapy (HAART)
      induced hepatotoxicity appear to be the major causes of liver disease in this
      population, other diseases endemic to Africa with hepatic manifestations are
      influenced by HIV infection as well. In this review we present the available data
      on liver disease in HIV-infected populations in Africa and discuss relevant data
      from the rest of the world. In addition, we highlight important areas for further
      study.

PMID- 16430202
TI  - TAK-652, a novel CCR5 inhibitor, has favourable drug interactions with other
      antiretrovirals in vitro.

PMID- 16430204
TI  - Conformational relaxation of single bacterial light-harvesting complexes.
AB  - We have employed the technique of single-molecule fluorescence microspectroscopy
      to investigate the spontaneous conformational evolution of individual peripheral
      LH2 complexes from the purple bacterium Rhodopseudomonas acidophila. Fluorescence
      microscopy is a sensitive tool, which allows the spectral changes of single
      complexes to be monitored on a time scale from 0.1 s to many minutes. Here we
      have investigated "natural" (occurring in the absence of excitation) spectral
      diffusion after a spectral jump has occurred. In a quarter of all the observed
      spectral jumps recorded with the LH2 complexes, a further spontaneous evolution
      occurs, in the absence of illumination, that results in the formation of a
      different spectroscopic state. We suggest that this is due to a natural
      conformational development of the pigment-protein complex, which so far has not
      been observed for this type of complex at the single-molecule level. The
      functional significance of such structural rearrangements is not yet clear but
      may be associated with the necessity for the light-harvesting complexes to adjust
      their shape in the densely packed photosynthetic membrane.

PMID- 16430203
TI  - Utility of a fluorescent vitamin E analogue as a probe for tocopherol transfer
      protein activity.
AB  - The tocopherol transfer protein (TTP) is a member of the CRAL-TRIO family of
      lipid binding proteins that facilitates vitamin E transfer between membrane
      vesicles in vitro. In cultured hepatocytes, TTP enhances the secretion of
      tocopherol to the media; presumably, tocopherol transfer is at the basis of this
      biological activity. The mechanism underlying ligand transfer by TTP is presently
      unknown, and available tools for monitoring this activity suffer from complicated
      assay procedure and poor sensitivity. We report the characterization of a
      fluorescent vitamin E analogue, (R)-2,5,7,8-tetramethylchroman-2-[9-(7
      nitrobenz[1,2,5]oxadiazol-4-ylamino)nonyl]chroman-6-ol (NBD-TOH), as a sensitive
      and convenient probe for the ligand binding and transfer activities of TTP. Upon
      binding to TTP, NBD-TOH fluorescence is blue shifted, and its intensity is
      greatly enhanced. We used these properties to accurately determine the affinity
      of NBD-TOH to TTP. The analogue binds to TTP reversibly and with high affinity
      (K(d) = 8.5 +/- 6 nM). We determined the affinity of NBD-TOH to a TTP protein in
      which lysine 59 is replaced with a tryptophan. When occurring in humans, this
      heritable mutation causes the ataxia with vitamin E deficiency (AVED) disorder.
      We find that the affinity of NBD-TOH to this mutant TTP is greatly diminished
      (K(d) = 71 +/- 19 nM). NBD-TOH functioned as a sensitive fluorophore in
      fluorescent resonance energy transfer (FRET) experiments. Using the fluorescent
      lipids TRITC-DHPE or Marina Blue-DHPE as a donor or an acceptor for NBD-TOH
      fluorescence, we obtained high-resolution kinetic data for tocopherol movement
      out of lipid bilayers, a key step in the TTP-facilitated ligand transfer
      reaction.

PMID- 16430205
TI  - Studies of nucleoside transporters using novel autofluorescent nucleoside probes.
AB  - To better understand nucleoside transport processes and intracellular fates of
      nucleosides, we have developed a pair of fluorescent nucleoside analogues, FuPmR
      and dFuPmR, that differ only in the sugar moiety (ribofuranosyl versus 2'-deoxy,
      respectively), for real-time analysis of nucleoside transport into living cells
      by confocal microscopy. The binding and transportability of the two compounds
      were assessed for five recombinant human nucleoside transporters (hENT1/2,
      hCNT1/2/3) produced in Saccharomyces cerevisiae and/or oocytes of Xenopus laevis.
      The ribosyl derivative (FuPmR) was used to demonstrate proof of principle in live
      cell imaging studies in 11 cultured human cancer cell lines with different hENT1
      activities. The autofluorescence emitted from FuPmR enabled direct visualization
      of its movement from the extracellular medium into the intracellular compartment
      of live cells, and this process was blocked by inhibitors of hENT1
      (nitrobenzylmercaptopurine ribonucleoside, dipyridamole, and dilazep).
      Quantitative analysis of fluorescence signals revealed two stages of FuPmR
      uptake: a fast first stage that represented the initial uptake rate (i.e.,
      transport rate) followed by a slow long-lasting second stage. The accumulation of
      FuPmR and/or its metabolites in nuclei and mitochondria was also visualized by
      live cell imaging. Measurements of fluorescence intensity increases in nuclei and
      mitochondria revealed rate-limited processes of permeant translocation across
      intracellular membranes, demonstrating for the first time the intracellular
      distribution of nucleosides and/or nucleoside metabolites in living cells. The
      use of autofluorescent nucleosides in time-lapse confocal microscopy is a novel
      strategy to quantitatively study membrane transport of nucleosides and their
      metabolites that will provide new knowledge of nucleoside biology.

PMID- 16430206
TI  - Interactions of granisetron with an agonist-free 5-HT3A receptor model.
AB  - A new homology model of type-3A serotonin receptors (5-HT(3A)Rs) was built on the
      basis of the electron microscopic structure of the nicotinic acetylcholine
      receptor and with an agonist-free binding cavity. The new model was used to re
      evaluate the interactions of granisetron, a 5-HT(3A)R antagonist. Docking of
      granisetron identified two possible binding modes, including a newly identified
      region for antagonists formed by loop B, C, and E residues. Amino acid residues
      L184-D189 in loop B were mutated to alanine, while Y143 and Y153 in loop E were
      mutated to phenylalanine. Mutation H185A resulted in no detectable granisetron
      binding, while D189A resulted in a 22-fold reduction in affinity. Y143F and Y153F
      decreased granisetron affinity to the same extent as Y143A and Y153A mutations,
      supporting the role of the OH groups of these tyrosines in loop E. Modeling and
      mutation studies suggest that granisetron plays its antagonist role by hindering
      the closure of the back wall of the binding cavity.

PMID- 16430207
TI  - Asymmetric usage of antagonist charged residues drives interleukin-5 receptor
      recruitment but is insufficient for receptor activation.
AB  - The cyclic peptide AF17121 (VDECWRIIASHTWFCAEE) is a library-derived antagonist
      for human Interleukin-5 receptor alpha (IL5Ralpha). We have previously
      demonstrated that AF17121 mimics Interleukin-5 (IL5) by binding in a region of
      IL5Ralpha that overlaps the IL5 binding epitope. In the present study, to explore
      the functional importance of the amino acid residues of AF17121 required for
      effective binding to, and antagonism of, IL5Ralpha, each charged residue was
      subjected to site-directed mutagenesis and examined for IL5Ralpha interaction by
      using a surface plasmon resonance biosensor. One residue, Arg(6), was found to be
      essential for receptor antagonism; its replacement with either alanine or lysine
      completely abolished the interaction between AF17121 and IL5Ralpha. Other charged
      residues play modulatory roles. One class consists of the N-terminal acidic
      cluster (Asp(2) and Glu(3)) for which alanine replacement decreased the
      association rate. A second class consists of His(11) and the C-terminal acidic
      cluster (Glu(17) and Glu(18)) for which alanine replacement increased the
      dissociation rate. Binding model analysis of the mutants of the latter class of
      residues indicated the existence of conformational rearrangement during the
      interaction. On the basis of these results, we propose a model in which Arg(6)
      and N-terminal acidic residues drive the encounter complex, while Arg(6),
      His(11), and C-terminal acidic residues are involved in stabilizing the final
      complex. These data argue that the charged residues of AF17121 are utilized
      asymmetrically in the pathway of inhibitor-receptor complex formation to
      deactivate the receptor function. The results also help focus emerging models for
      the mechanism by which IL5 activates the IL5Ralpha-betac receptor system.

PMID- 16430208
TI  - Probing the impact of valency on the routing of arginine-rich peptides into
      eukaryotic cells.
AB  - Multivalency represents a critical parameter in cell biology responsible for the
      overall avidity of low-affinity interactions and the triggering of cellular
      events. Functions such as catalytic activity, cellular uptake, or localization
      are frequently linked to the oligomeric state of a protein. This study explores
      the impact of multivalency on the import and routing of peptides into cells.
      Specifically, cationic import sequences such as decaarginine, decalysine, and the
      HIV Tat peptide (GRKKRRQRRRAP, residues 48-59) as well as the nuclear
      localization sequence from SV40 large T-antigen were assembled into defined
      peptide oligomers by fusing them to the tetramerization domain of human p53
      (residues 325-355, hp53(tet) domain). The resulting tetravalent peptides
      typically displayed between 10- and 100-fold enhancements in cellular import and
      intracellular routing properties in relation to their monomeric homologues. These
      peptides were not toxic to cells. Flow cytometry results and transfection assays
      indicated that tetravalent decaarginyl peptides (10R-p53(tet) and NLS-10R
      p53(tet)) were the peptides most efficiently routed into cells. Their mechanism
      of import was subsequently examined on unfixed, viable cells using a combination
      of metabolic inhibitors, flow cytometry, and microscopy techniques. These studies
      revealed that tetravalent arginine-rich peptides bind to heparan sulfate on the
      cell surface, are internalized at 37 degrees C, but not at 4 degrees C, via a
      clathrin-mediated pathway, and accumulate into endosome-like acidic compartments.
      A fraction of these tetravalent peptides access the cytosol and accumulate in the
      nucleus of cells. This study concludes that the oligomerization of proteins
      harboring arginine-rich peptide chains may profoundly influence their ability to
      enter and be routed into cells.

PMID- 16430209
TI  - Molecular characterization of human melanocortin-3 receptor ligand-receptor
      interaction.
AB  - Melanocortin-3 receptor (MC3R), primarily expressed in the hypothalamus, plays an
      important role in the regulation of energy homeostasis. MC3R-deficient (MC3R(
      )(/)(-)) mice demonstrate increased fat mass, higher feeding efficiency,
      hyperleptinaemia, and mild hyperinsulinism. At least one specific mutation of
      MC3R has been identified to be associated with human obesity. Functional analysis
      of this altered MC3R (I183N) has indicated that the mutation completely abolishes
      agonist-mediated receptor activation. However, the specific molecular
      determinants of MC3R responsible for ligand binding and receptor signaling are
      currently unknown. The present study is to determine the structural aspects of
      MC3R responsible for ligand binding and receptor signaling. On the basis of our
      theoretical model for MC1R, using mutagenesis, we have examined 19 transmembrane
      domain amino acids selected for these potential roles in ligand binding and
      receptor signaling. Our results indicate that (i) substitutions of charged amino
      acid residues E131 in transmembrane domain 2 (TM2), D154 and D158 in TM3, and
      H298 in TM6 with alanine dramatically reduced NDP-MSH binding affinity and
      receptor signaling, (ii) substitutions of aromatic amino acids F295 and F296 in
      TM6 with alanine also significantly decreased NDP-MSH binding and receptor
      activity, (iii) substitutions of D121in TM2 and D332 in TM7 with alanine resulted
      in the complete loss of ligand binding, ligand induced receptor activation, and
      cell surface protein expression, and (iv) interestingly, substitution of L165 in
      TM3 with methionine or alanine switched antagonist SHU9119 into a receptor
      agonist. IN CONCLUSION: Our results suggest that TM3 and TM6 are important for
      NDP-MSH binding, while D121 in TM2 and D332 in TM7 are crucial for receptor
      activity and signaling. Importantly, L165 in TM3 is critical for agonist or
      antagonist selectivity. These results provide important information about the
      molecular determinants of hMC3R responsible for ligand binding and receptor
      signaling.

PMID- 16430211
TI  - The crucial importance of chemistry in the structure-function link: manipulating
      hydrogen bonding in iron-containing superoxide dismutase.
AB  - Fe-containing superoxide dismutase's active site Fe is coordinated by a solvent
      molecule, whose protonation state is coupled to the Fe oxidation state. Thus, we
      have proposed that H-bonding between glutamine 69 and this solvent molecule can
      strongly influence the redox activity of the Fe in superoxide dismutase (SOD). We
      show here that mutation of this Gln to His subtly alters the active site
      structure but preserves 30% activity. In contrast, mutation to Glu otherwise
      preserves the active site structure but inactivates the enzyme. Thus, enzyme
      function correlates not with atom positions but with residue identity
      (chemistry), in this case. We observe strong destabilization of the Q69E-FeSOD
      oxidized state relative to the reduced state and intermediate destabilization of
      oxidized Q69H-FeSOD. Indeed, redox titrations indicate that mutation of Gln69 to
      His increases the reduction potential by 240 mV, whereas mutation to Glu appears
      to increase it by more than 660 mV. We find that this suffices to explain the
      mutants' loss of activity, although additional factors may also contribute. The
      strongly elevated reduction potential of Q69E-FeSOD may reflect reorganization of
      the active site H-bonding network, including possible reversal of the polarity of
      the key H-bond between residue 69 and coordinated solvent.

PMID- 16430210
TI  - Crystal structures of nitroalkane oxidase: insights into the reaction mechanism
      from a covalent complex of the flavoenzyme trapped during turnover.
AB  - Nitroalkane oxidase (NAO) from Fusarium oxysporum catalyzes the oxidation of
      neutral nitroalkanes to the corresponding aldehydes or ketones with the
      production of H(2)O(2) and nitrite. The flavoenzyme is a new member of the acyl
      CoA dehydrogenase (ACAD) family, but it does not react with acyl-CoA substrates.
      We present the 2.2 A resolution crystal structure of NAO trapped during the
      turnover of nitroethane as a covalent N5-FAD adduct (ES*). The homotetrameric
      structure of ES* was solved by MAD phasing with 52 Se-Met sites in an
      orthorhombic space group. The electron density for the N5-(2-nitrobutyl)-1,5
      dihydro-FAD covalent intermediate is clearly resolved. The structure of ES was
      used to solve the crystal structure of oxidized NAO at 2.07 A resolution. The c
      axis for the trigonal space group of oxidized NAO is 485 A, and there are six
      subunits (1(1)/(2) holoenzymes) in the asymmetric unit. Four of the active sites
      contain spermine (EI), a weak competitive inhibitor, and two do not contain
      spermine (E(ox)). The active-site structures of E(ox), EI, and ES* reveal a
      hydrophobic channel that extends from the exterior of the protein and terminates
      at Asp402 and the N5 position on the re face of the FAD. Thus, Asp402 is in the
      correct position to serve as the active-site base, where it is proposed to
      abstract the alpha proton from neutral nitroalkane substrates. The structures for
      NAO and various members of the ACAD family overlay with root-mean-square
      deviations between 1.7 and 3.1 A. The homologous region typically spans more than
      325 residues and includes Glu376, which is the active-site base in the
      prototypical member of the ACAD family. However, NAO and the ACADs exhibit
      differences in hydrogen-bonding patterns between the respective active-site base,
      substrate molecules, and FAD. These likely differentiate NAO from the homologues
      and, consequently, are proposed to result in the unique reaction mechanism of
      NAO.

PMID- 16430212
TI  - Kinetic analysis of Pseudomonas aeruginosa arginine deiminase mutants and
      alternate substrates provides insight into structural determinants of function.
AB  - L-Arginine deiminase from Pseudomonas aeruginosa (PaADI) catalyzes the hydrolysis
      of arginine to citrulline and ammonia. PaADI belongs to the guanidino group
      modifying enzyme superfamily (GMSF), which conserves backbone fold and a Cys-,
      His-, and Asp-based catalytic core. In this paper the contributions made by the
      PaADI core residues Cys406, His278, and Asp166 and the contribution from the
      neighboring Asp280 (conserved in most but not all GMSF members) to catalysis of
      the formation and hydrolysis of the Cys406-alkyluronium intermediate were
      accessed by kinetic analysis of site-directed mutants. In addition, solution
      hydrolysis in a chemical model of the S-alkylthiouronium intermediate was
      examined to reveal the importance of general base catalysis in the enzymatic
      reaction. Substitutions of the active site gating residue Arg401, the l-arginine
      C(alpha)NH(3)(+)(COO(-)) binding residues, Arg185, Arg243, and Asn160, or the
      His278 hydrogen bond partner, Glu224, were found to cause dramatic reductions in
      the enzyme turnover rate. These results are interpreted to suggest that
      electrostatic interactions play a dominant role in PaADI catalysis. Structural
      variations observed in P. aeruginosa GMSF enzymes PaADI, agmatine deiminase
      (PaAgDI), and N(omega),N(omega)-dimethylarginine dimethylaminohydrolase (PaDDAH)
      indicate an early divergence of the encoding genes. Arginine analogues that are
      known substrates for PaAgDI and PaDDAH were tested with PaADI to define clear
      boundaries of biochemical function in the three hydrolases. The conservation of a
      catalytic core associated with the common chemical function and the divergence of
      substrate-binding residues (as well as one key catalytic residue) to expand the
      substrate range provide insight into the evolution of the catalysts that form the
      GMSF.

PMID- 16430214
TI  - Structure and activity analyses of Escherichia coli K-12 NagD provide insight
      into the evolution of biochemical function in the haloalkanoic acid dehalogenase
      superfamily.
AB  - The HAD superfamily is a large superfamily of proteins which share a conserved
      core domain that provides those active site residues responsible for the
      chemistry common to all family members. The superfamily is further divided into
      the four subfamilies I, IIA, IIB, and III, based on the topology and insertion
      site of a cap domain that provides substrate specificity. This structural and
      functional division implies that members of a given HAD structural subclass may
      target substrates that have similar structural characteristics. To understand the
      structure/function relationships in all of the subfamilies, a type IIA subfamily
      member, NagD from Escherichia coli K-12, was selected (type I, IIB, and III
      members have been more extensively studied). The structure of the NagD protein
      was solved to 1.80 A with R(work) = 19.8% and R(free) = 21.8%. Substrate
      screening and kinetic analysis showed NagD to have high specificity for
      nucleotide monophosphates with k(cat)/K(m) = 3.12 x 10(4) and 1.28 x 10(4)
      microM(-)(1) s(-)(1) for UMP and GMP, respectively. This specificity is
      consistent with the presence of analogues of NagD that exist as fusion proteins
      with a nucleotide pyrophosphatase from the Nudix family. Docking of the
      nucleoside substrate in the active site brings it in contact with conserved
      residues from the cap domain that can act as a substrate specificity loop (NagD
      residues 144-149) in the type IIA subfamily. NagD and other subfamily IIA and IIB
      members show the common trait that substrate specificity and catalytic
      efficiencies (k(cat)/K(m)) are low (1 x 10(4) M(-)(1) s(-)(1)) and the boundaries
      defining physiological substrates are somewhat overlapping. The ability to
      catabolize other related secondary metabolites indicates that there is regulation
      at the genetic level.

PMID- 16430213
TI  - Loop motions of triosephosphate isomerase observed with elastic networks.
AB  - The internal dynamics of triosephosphate isomerase have been investigated with
      elastic networks, with and without a substrate bound. The slowest modes of motion
      involve large domain motions but also a loop motion that conforms to the changes
      observed between the crystal structures and . Our computations confirm that the
      different motions of this loop are important in several of the computed slowest
      modes. We have shown that elastic network computations on this protein system can
      combine atoms for the functional parts of the structure with coarse-grained (cg)
      representations of the remainder of the structure in several different ways.
      Similar loop motions are seen with elastic network models for atomistic and mixed
      cg models. The loop motions are reproduced with an overlap of 0.75-0.79 by
      combining the four slowest modes of motion for the free and complex forms of the
      enzyme.

PMID- 16430215
TI  - Deoxyribozyme-based three-input logic gates and construction of a molecular full
      adder.
AB  - We have developed an array of seven deoxyribozyme-based molecular logic gates
      that behaves as a full adder in a single solution, with three oligonucleotides as
      inputs and two independent fluorogenic cleavage reactions as carry and sum
      outputs. The sum output consisted of four new deoxyribozyme-based logic gates: an
      ANDAND gate and three ANDNOTANDNOT gates. These gates required the design of a
      generic three-input deoxyribozyme-based logic gate that can use any three-way
      combination of activating or inactivating inputs. This generic gate design
      utilizes an additional inverting element that hybridizes to convert YES logic
      into NOT logic and vice versa. The system represents the first solution-phase,
      single test tube, enzymatic full adder and shows the complexity of control over
      molecular scale events that can be achieved with deoxyribozyme-based logic gates.
      Similar systems could be applied to control autonomous therapeutic and diagnostic
      devices.

PMID- 16430216
TI  - Interaction between the Z-type DNA duplex and 1,3-propanediamine: crystal
      structure of d(CACGTG)2 at 1.2 A resolution.
AB  - The crystal structure of a hexamer duplex d(CACGTG)(2) has been determined and
      refined to an R-factor of 18.3% using X-ray data up to 1.2 A resolution. The
      sequence crystallizes as a left-handed Z-form double helix with Watson-Crick base
      pairing. There is one hexamer duplex, a spermine molecule, 71 water molecules,
      and an unexpected diamine (Z-5, 1,3-propanediamine, C(3)H(10)N(2)) in the
      asymmetric unit. This is the high-resolution non-disordered structure of a Z-DNA
      hexamer containing two AT base pairs in the interior of a duplex with no
      modifications such as bromination or methylation on cytosine bases. This
      structure does not possess multivalent cations such as cobalt hexaammine that are
      known to stabilize Z-DNA. The overall duplex structure and its crystal
      interactions are similar to those of the pure-spermine form of the d(CGCGCG)(2)
      structure. The spine of hydration in the minor groove is intact except in the
      vicinity of the T5A8 base pair. The binding of the Z-5 molecule in the minor
      grove of the d(CACGTG)(2) duplex appears to have a profound effect in conferring
      stability to a Z-DNA conformation via electrostatic complementarity and hydrogen
      bonding interactions. The successive base stacking geometry in d(CACGTG)(2) is
      similar to the corresponding steps in d(CG)(3). These results suggest that
      specific polyamines such as Z-5 could serve as powerful inducers of Z-type
      conformation in unmodified DNA sequences with AT base pairs. This structure
      provides a molecular basis for stabilizing AT base pairs incorporated into an
      alternating d(CG) sequence.

PMID- 16430218
TI  - Cholesterol hydroxyl group is found to reside in the center of a polyunsaturated
      lipid membrane.
AB  - Cholesterol and saturated lipid species preferentially partition into liquid
      ordered microdomains, such as lipid rafts, away from unsaturated lipid species
      for which the sterol has less affinity in the surrounding liquid-disordered
      membrane. To observe how cholesterol interacts with unsaturated phospholipids, we
      have determined, from one-dimensional neutron scattering length density profiles,
      the depth of cholesterol in phosphatidylcholine (PC) bilayers with varying
      amounts of acyl chain unsaturation. Through the use of [2,2,3,4,4,6-(2)H(6)]
      labeled cholesterol, we show that in 1-palmitoyl-2-oleoylphosphatidylcholine
      (16:0-18:1 PC), 1,2-dioleoylphosphatidylcholine (18:1-18:1 PC), and 1-stearoyl-2
      arachidonylphosphatidylcholine (18:0-20:4 PC) bilayers the center of mass of the
      deuterated sites is approximately 16 A from the bilayer center. This location
      places the hydroxyl group of the sterol moiety at the hydrophobic/hydrophilic
      bilayer interface, which is the generally accepted position. In dramatic
      contrast, for 20:4-20:4 PC membranes the hydroxyl group is found, unequivocally,
      sequestered in the bilayer center. We attribute the change in location to the
      high disorder of polyunsaturated fatty acids (PUFA) that is incompatible with
      close proximity to the steroid moiety in its usual "upright" orientation.

PMID- 16430217
TI  - Role of nuclear chromogranin B in inositol 1,4,5-trisphosphate-mediated nuclear
      Ca2+ mobilization.
AB  - Recently, secretory granule Ca(2+) storage protein chromogranin B (CGB) was shown
      to be present in the nucleoplasm proper in a complex structure that consists of
      the inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+) channels and the
      phospholipids. Further, the amounts of IP(3)Rs present in the nucleus of bovine
      chromaffin cells were shown to be comparable to that of the endoplasmic
      reticulum. Therefore, we investigated here the potential contribution of nuclear
      CGB on the IP(3)-dependent Ca(2+) mobilization in the nucleus, using both
      neuroendocrine PC12 and nonneuroendocrine NIH3T3 cells. Chromogranin A (CGA)
      expression in the NIH3T3 cells, which do not contain intrinsic chromogranins,
      increased the IP(3)-induced Ca(2+) releases in the nucleus by 45%, while CGB
      expression in the same cells increased the IP(3)-induced Ca(2+) releases in the
      nucleus by 80%. Microinjection of IP(3) into the nucleus of CGB-expressing NIH3T3
      cells increased the IP(3)-dependent nuclear Ca(2+) mobilization approximately 3
      fold, whereas in CGA-expressing cells it remained the same as that of control
      cells. In contrast, inhibition of CGA expression in PC12 cells by siRNA treatment
      decreased the IP(3)-induced Ca(2+) releases in the nucleus by 17%, while
      inhibition of CGB expression decreased the IP(3)-induced Ca(2+) releases in the
      nucleus by 55%. Microinjection of IP(3) into the nucleus of siCGB-treated PC12
      cells decreased the IP(3)-dependent nuclear Ca(2+) mobilization by approximately
      75%, whereas in siCGA-treated cells it remained the same as that of control
      cells. Given the presence of CGB in the nucleus, these results further highlight
      the critical contribution of nuclear CGB in the IP(3)-induced Ca(2+) release in
      the nucleus.

PMID- 16430219
TI  - The interaction of Phe472 with a fluorescent inhibitor bound to the complex of
      myosin subfragment-1 with nucleotide.
AB  - The fluorescent probe 3-[4-(3-phenyl-2-pyrazolin-1-yl)benzene-1-sulfonyl
      amido]phenylboronic acid (PPBA) acts as a fluorescent inhibitor for the ATPases
      of skeletal [Hiratsuka (1994) J. Biol. Chem. 269, 27251-27257] and Dictyostelium
      discoideum [Bobkov et al. (1997) J. Muscle Res. Cell Motil. 18, 563-571] myosins.
      The former paper suggested that, upon addition of excess nucleotides to the
      binary complex of subfragment-1 from skeletal myosin (S1) with PPBA, a stable
      ternary complex of S1 with PPBA and nucleotide is formed. Useful fluorescence
      properties of PPBA enable us to distinguish the conformation of the myosin ATPase
      at the ATP state from that at the ADP state. In the present paper, to determine
      the PPBA-binding site in the complexes, enzymatic and fluorescence properties of
      the S1.PPBA.nucleotide complexes were investigated. Upon formation of the ternary
      complex with ATP, a new peak appeared at 398 nm in the PPBA fluorescence
      spectrum. Experiments using model compounds of aromatic amino acid suggested that
      this fluorescence peak at 398 nm is originated from PPBA interacting with Phe
      residue(s). Taking into account differences in fluorescence spectra between
      complexes of S1 and those of subfragment-1 from D. discoideum myosin (S1dC), in
      the ternary complex of S1 formed with ATP, PPBA was suggested to interact with
      Phe residue(s) that is absent in S1dC. Docking simulation of PPBA on the
      S1.nucleotide complex revealed that Phe472 interacts with PPBA. Binding sites of
      PPBA and blebbistatin, an inhibitor showing high affinity and selectivity toward
      myosin II [Kovacs et al. (2004) J. Biol. Chem. 279, 35557-35563], seem to overlap
      at least partly.

PMID- 16430221
TI  - Myeloperoxidase metabolizes thiocyanate in a reaction driven by nitric oxide.
AB  - We examined the potential physiological relevance of myeloperoxidase (MPO)-nitric
      oxide (NO) interactions as they may relate to the cosubstrate, pseudo halide
      thiocyanate (SCN(-)), and substrate switching. Direct spectroscopic and rapid
      kinetics studies revealed that SCN(-) interaction with MPO facilitates formation
      of the MPO catalytic intermediate Compound II, limiting overall activity.
      However, a physiological NO concentration (2 microM or less) dramatically
      influences the build-up, duration, and decay of the steady-state level of MPO
      Compound II during the metabolism of SCN(-), allowing the enzyme to function at
      full capacity. At higher NO concentrations, we observed significant increases in
      the rate of MPO Compound II formation, along with proportional increases in its
      duration as determined by the time elapsed during catalysis. Surprisingly, the
      decay rate of MPO Compound II remained unaltered as NO concentrations were
      increased. Computer simulations were carried out to model the kinetics of MPO
      Compound II formation, duration, and decay during the metabolism of SCN(-) as a
      function of NO concentration. These simulation traces closely approximate what
      was observed experimentally and support the involvement of a conformational
      intermediate of MPO Compound II complex decay, altering the overall capacity of
      MPO to promote two electrons versus one-electron oxidation reactions during
      steady-state catalysis. Collectively, the present studies reveal that
      (patho)physiologically relevant levels of NO have significant effects on MPO
      Compound II accumulation. Thus, NO affects the overall rate of peroxidation of
      substrates and the overall ability of the peroxidase to execute one- versus two
      electron oxidation reactions.

PMID- 16430220
TI  - Structure and stability of apolipoprotein a-I in solution and in discoidal high
      density lipoprotein probed by double charge ablation and deletion mutation.
AB  - To identify residues and segments in the central region of apolipoprotein A-I
      (apoA-I) that are important for the protein structure and stability, we studied
      the effects of four double charge ablations, D102A/D103A, E110A/E111A,
      R116V/K118A, and R160V/H162A, and two deletion mutations, Delta(61-78) and
      Delta(121-142), on the conformation and stability of apoA-I in the lipid-free
      state and in reconstituted discoidal phospholipid-cholesterol-apoA-I particles
      (rHDL). The findings suggest that D102/D103 and E110/E111 located in helix 4 and
      segment(s) between residues 61 and 78 are involved in maintenance of the
      conformation and stability of apoA-I in both the lipid-free state and in rHDL.
      R116/K118 located in helix 4 are essential for the conformation and stabilization
      of apoA-I in rHDL but not vital for the lipid-free state of the protein. The
      R160V/H162A substitutions in helix 6 lead to a less compact tertiary structure of
      lipid-free apoA-I without notable effects on the lipid-free or lipid-bound
      secondary conformation, suggesting involvement of R160/H162 in important
      interhelical interactions. The results on the Delta(121-142) mutant, together
      with our earlier findings, suggest disordered structure of a major segment
      between residues 121 and 143, likely including residues 131-143, in lipid-free
      apoA-I. Our findings provide the first experimental evidence for stabilization of
      rHDL by specific electrostatic interhelical interactions, in agreement with the
      double belt model. The effects of alterations in the conformation and stability
      of the apoA-I mutants on in vitro and in vivo functions of apoA-I and lipid
      homeostasis are discussed.

PMID- 16430222
TI  - Influence of acylation of a Peptide corresponding to the amino-terminal region of
      endothelial nitric oxide synthase on the interaction with model membranes.
AB  - Covalent attachment of fatty acids to proteins is a common form of protein
      modification which has been shown to influence both structure and interaction
      with membranes. Endothelial nitric oxide synthase (eNOS) is dually acylated by
      the fatty acids myristate and palmitate. We have synthesized four peptides
      corresponding to the first 28 amino acids of the N-terminal region of eNOS.
      Besides the nonacylated eNOS sequence, three additional peptides with different
      degrees of acylation have been obtained: myristoylated, doubly palmitoylated, and
      dually myristoylated and doubly palmitoylated. Acylation itself, myristic and/or
      palmitic, confers the peptide the ability to adopt extended conformations,
      indicated by the fact that the CD spectrum of all acylated peptides has a minimum
      at approximately 215 nm characteristic of beta-sheet structure. The nonacylated
      sequence interacts with model membranes composed of acidic phospholipids probably
      through ionic interactions with the polar headgroup of the phospholipids.
      However, the acylated peptides are able to insert deeply into the hydrophobic
      core of both neutral and acidic phospholipids, maintaining the spectral features
      of extended conformations. When DMPC vesicles containing cholesterol and
      sphingomyelin at 10% were used, the insertion of the triacylated peptide almost
      completely canceled the thermal transition, although the interaction of the other
      acylated peptides also reduced the transition amplitude but to a much lower
      extent and affected only the acyl chains in the fluid state.

PMID- 16430223
TI  - Salmonella enterica SpvB ADP-ribosylates actin at position arginine-177
      characterization of the catalytic domain within the SpvB protein and a comparison
      to binary clostridial actin-ADP-ribosylating toxins.
AB  - The SpvB protein from Salmonella enterica was recently discovered as an actin-ADP
      ribosylating toxin. SpvB is most likely delivered via a type-III secretion system
      into eukaryotic cells and does not have a binding/translocation component. This
      is in contrast to the family of binary actin-ADP-ribosylating toxins from various
      Bacillus and Clostridium species. However, there are homologies in amino acid
      sequences between the C-terminal domain of SpvB and the catalytic domains of the
      actin-ADP-ribosylating toxins such as C2 toxin from Clostridium botulinum and
      iota toxin from Clostridium perfringens. We compared the biochemical properties
      of the catalytic C-terminal domain of SpvB (C/SpvB) with the enzyme components of
      C2 toxin and iota toxin. The specificity of C/SpvB concerning the modification of
      G- or F-actin was comparable to the C2 and iota toxins, although there were
      distinct differences regarding the recognition of actin isoforms. C/SpvB and iota
      toxin modify both muscle alpha-actin and nonmuscle beta/gamma-actin, whereas C2
      toxin only modifies beta/gamma-actin. In contrast to the iota and C2 toxins,
      C/SpvB possessed no detectable glycohydrolase activity in the absence of a
      protein substrate. The maximal reaction rates were comparable for all toxins,
      whereas variable K(m) values for NAD were evident. We identified arginine-177 as
      the modification site for C/SpvB with the actin homologue protein Act88F from
      Drosophila.

PMID- 16430224
TI  - A thaumatin-like protein from larvae of the beetle Dendroides canadensis enhances
      the activity of antifreeze proteins.
AB  - The levels of thermal hysteresis (antifreeze activity) produced by purified
      antifreeze proteins (DAFPs) from the larvae of the beetle Dendroides canadensis
      at endogenous concentrations are lower than what are present in the hemolymph of
      overwintering larvae. Thermal hysteresis activity of DAFPs is dependent not only
      on AFP concentration but also on the presence of enhancers that may be either
      proteins (including other hemolymph DAFPs) or low-molecular mass enhancers such
      as glycerol. The purpose of this study was to identify endogenous protein
      enhancers using yeast two-hybrid, co-immunoprecipitation, and finally the
      enhancement of antifreeze activity. Here we show that a thaumatin-like protein
      from D. canadensis, until recently known only from plants, significantly enhances
      the thermal hysteresis of DAFP-1 and -2. Glycerol can further this enhancement,
      presumably by promoting the interaction of the DAFPs and thaumatin-like protein.

PMID- 16430225
TI  - Assignment of the vibrational modes of the chromophores of iodopsin and
      bathoiodopsin: low-temperature fourier transform infrared spectroscopy of 13C-
      and 2H-labeled iodopsins.
AB  - To investigate the chromophore structures of iodopsin and its low-temperature
      photoproducts, we have assigned their vibrational bands in the Fourier transform
      infrared (FTIR) spectra using iodopsin samples that were reconstituted with a
      series of (13)C- and deuterium-labeled retinals. The analyses of the vibrational
      bands in the fingerprint and hydrogen-out-of-plane (HOOP) regions indicated that
      the structure of the chromophores in the iodopsin system differs near their
      centers from those in the rhodopsin system. Compared to rhodopsin, the
      chromophore of the batho intermediate of iodopsin is twisted in the C(12) to
      C(14) regions but is more planar around C(11) region. The large amount of
      twisting was reduced by removing the chloride ion from the iodopsin, suggesting
      that this twisting hinders the relaxation of the torsion near C(11) necessary for
      the transition to the lumi intermediate and thus results in the thermal reversion
      of the batho intermediate back to the iodopsin. From the analyses of the C=NH and
      C=ND stretching bands, we conclude that the displacement of the Schiff base
      region upon photoisomerization of the chromophore is restricted, as is the case
      for rhodopsin. These results indicated that iodopsin's chromophore has a unique
      structure near its center and that this difference is enhanced by the binding of
      chloride nearby.

PMID- 16430226
TI  - A sensitive method for determining the phosphorylation status of natriuretic
      peptide receptors: cGK-Ialpha does not regulate NPR-A.
AB  - Natriuretic peptide receptor A (NPR-A) and natriuretic peptide receptor B (NPR-B)
      are transmembrane guanylyl cyclases that catalyze the synthesis of cGMP in
      response to natriuretic peptides. Phosphorylation and dephosphorylation regulate
      these receptors and have been traditionally studied by (32)PO(4) labeling of
      transfected cells. However, this approach cannot be used to determine the
      phosphorylation state of receptors isolated from unlabeled sources. Here, we use
      Pro-Q Diamond and SYPRO Ruby dyes to quantify the phosphorylation status and
      protein levels, respectively, of natriuretic peptide receptors from tissues and
      cells. Strong Pro-Q Diamond signals for NPR-A and NPR-B were obtained when
      receptors were isolated from lung tissue, liver tissue and overexpressing cells.
      The level of NPR-A Pro-Q staining was also high in kidney but was much lower in
      heart tissue. In contrast, the SYPRO Ruby protein signal was weaker and more
      variable. In a direct comparison, Pro-Q Diamond staining was as sensitive as but
      more specific than the (32)PO(4) labeling method. The two approaches were highly
      correlated (R(2) = 0.98). We exploited these techniques to measure the effect of
      cGMP-dependent protein kinase Ialpha on the phosphate content and guanylyl
      cyclase activity of NPR-A. Neither value was significantly affected in cells
      overexpressing cGK-Ialpha or in tissues from mice lacking cGK-I. We conclude that
      cGK-I does not regulate the cyclase activity or phosphorylation state of NPR-A.
      Furthermore, we find that Pro-Q Diamond staining is a sensitive method for
      measuring the phosphate levels of natriuretic peptide receptors, but protein
      levels are best detected by Western blot analysis, not SYPRO Ruby staining.

PMID- 16430227
TI  - Definition and characterization of the short alphaA-conotoxins: a single residue
      determines dissociation kinetics from the fetal muscle nicotinic acetylcholine
      receptor.
AB  - We report the definition and characterization of a conotoxin subfamily,
      designated the short alphaA-conotoxins (alphaA(S)) and demonstrate that all of
      these share the unique property of selectively antagonizing the fetal subtype of
      the mammalian neuromuscular nicotinic acetylcholine receptor (nAChR). We have
      characterized newly identified alphaA(S)-conotoxins from Conus pergrandis and
      have conducted a more detailed characterization of alphaA-conotoxins previously
      reported from additional Conus species. Among the results, the characterization
      of the short alphaA-conotoxins revealed diverse kinetics of a block of the fetal
      muscle nAChR, particularly in dissociation rates. The structure-function
      relationships of native alphaA(S)-conotoxins and some analogues revealed a single
      amino acid locus (alternatively either His or Pro in native peptides) that is a
      critical determinant of the dissociation kinetics. The unprecedented binding
      selectivity for the fetal muscle nAChR, coupled with the kinetic diversity,
      should make alphaA(S)-conotoxins useful ligands for a diverse set of studies. The
      rapidly reversible peptides may be most suitable for electrophysiological
      studies, while the relatively irreversible peptides should be most useful for
      binding and localization studies.

PMID- 16430229
TI  - Heterologous production of epothilone C and D in Escherichia coli.
AB  - The epothilones are a family of polyketide natural products that show a high
      potential as anticancer drugs. They are synthesized by the action of a hybrid
      nonribosomal peptide synthetase/polyketide synthase in the myxobacterium
      Sorangium cellulosum. In this work, the genes encoding the entire cluster,epoA,
      epoB, epoC, epoD, epoE, and epoF, were redesigned and synthesized to allow for
      expression in Escherichia coli. The expression of the largest of the proteins,
      EpoD, also required the protein be separated into two polypeptides with
      compatible module linkers. Using a combination of lowered temperature, chaperone
      coexpression, and alternative promoters, we succeeded in producing a soluble
      protein from all genes in the epothilone cluster. The entire synthetic epothilone
      cluster was then expressed in a strain of E. coli modified to enable polyketide
      biosynthesis, resulting in the production of epothilones C and D. Furthermore,
      feeding a thioester of the normal substrate for EpoD to cells expressing the
      epoD, epoE, and epoF genes also led to the production of epothilones C and D. The
      design of the synthetic epothilone genes together with E. coli expression
      provides the ideal platform for both the biochemical investigation of the
      epothilone PKS and the generation of novel biosynthetic epothilone analogues.

PMID- 16430228
TI  - Sequential binding of cobalt(II) to metallo-beta-lactamase CcrA.
AB  - In an effort to probe Co(II) binding to metallo-beta-lactamase CcrA, EPR, EXAFS,
      and (1)H NMR studies were conducted on CcrA containing 1 equiv (1-Co(II)-CcrA)
      and 2 equiv (Co(II)Co(II)-CcrA) of Co(II). The EPR spectra of 1-Co(II)-CcrA and
      Co(II)Co(II)-CcrA are distinct and indicate 5/6-coordinate Co(II) ions. The EPR
      spectra also reveal the absence of significant spin-exchange coupling between the
      Co(II) ions in Co(II)Co(II)-CcrA. EXAFS spectra of 1-Co(II)-CcrA suggest 5/6
      coordinate Co(II) with two or more histidine ligands. EXAFS spectra of
      Co(II)Co(II)-CcrA also indicate 5/6 ligands at a similar average distance to 1
      Co(II)-CcrA, including an average of about two histidines per Co(II). (1)H NMR
      spectra for 1-Co(II)-CcrA revealed seven paramagnetically shifted resonances,
      three of which were solvent-exchangeable, while the NMR spectra for Co(II)Co(II)
      CcrA showed at least 16 shifted resonances, including an additional solvent
      exchangeable resonance and a resonance at 208 ppm. The data indicate sequential
      binding of Co(II) to CcrA and that the first Co(II) binds to the consensus Zn(1)
      site in the enzyme.

PMID- 16430230
TI  - The C-terminus is critical for the functional expression of the human serotonin
      transporter.
AB  - The plasma membrane serotonin transporter (SERT) has an important role in
      terminating serotonergic neurotransmission by re-uptake of 5-HT from the synaptic
      cleft. The expression of SERT on the cell surface is therefore a critical factor.
      In this study, we examined the role of the carboxyl terminus of SERT in
      trafficking to the plasma membrane. 5-HT uptake activity was used to measure the
      effects of systematic deletions or alanine substitutions in the C-terminus. We
      found that deletion of 16 amino acids in the distal C-terminus had no effect on
      uptake activity, whereas further deletion was detrimental for the function of
      SERT. Cell surface biotinylation was used to determine the role of the C-terminus
      in localization and trafficking. We showed that the C-terminus is crucial for the
      delivery of SERT to the plasma membrane and that the deletion of this part of the
      transporter results in a lack of mature glycosylation and impaired trafficking to
      the plasma membrane. Furthermore, the C-terminally truncated mutants were shown
      to have a dominant negative effect on wild-type SERT uptake activity.

PMID- 16430231
TI  - Two forms of human cytoplasmic arginyl-tRNA synthetase produced from two
      translation initiations by a single mRNA.
AB  - Human cytoplasmic arginyl-tRNA synthetase (ArgRS) is a component of a
      macromolecular complex consisting of at least nine tRNA synthetases and three
      auxiliary proteins. In mammalian cells, ArgRS is present as a free protein as
      well as a component of the complex. Via an alignment of ArgRSs from different
      vertebrates, the genes encoding full-length human cytoplasmic ArgRS and an N
      terminal 72-amino acid deletion mutant (hcArgRS and DeltaNhcArgRS, respectively)
      were subcloned and expressed in Escherichia coli. The two ArgRS products were
      expressed as a soluble protein in E. coli. The level of production of
      DeltaNhcArgRS in E. coli and its specific activity were higher than those for
      hcArgRS. By Western blot analysis, using an antibody against the purified
      DeltaNhcArgRS, the two forms of ArgRS were detected in three human cell types.
      The 5'-end cDNA sequence, as confirmed by 5'RACE (5'-rapid amplification of cDNA
      ends), contained three start codons. Through mutation of the three codons, the
      two human cytoplasmic ArgRSs were found to be produced in different amounts,
      indicating that they resulted from two different translation initiation events.
      Here we show evidence that two forms of human cytoplasmic ArgRS were produced
      from two translational initiations by a single mRNA.

PMID- 16430234
TI  - Photodestructible vesicles.
AB  - Stable vesicles are formed in a 1.4 wt % solution comprising a 1:3 mixture of the
      anionic photodestructible surfactant sodium 4-hexylphenylazosulfonate (C6PAS) and
      inert cationic cetyltrimethylamonium bromide (CTAB). UV irradiation drives an
      irreversible breakdown of the mixed C6PAS/CATB vesicles, owing to the selective
      degradation of C6PAS. A light-induced transition from small spherical-like
      polydisperse vesicles to long needle-like aggregation is observed.

PMID- 16430235
TI  - Preparation and characterization of a carbon nanotube-lyotropic liquid crystal
      composite.
AB  - We present a detailed study on the integration of individual single-walled carbon
      nanotubes (SWNTs) within a lyotropic hexagonal liquid crystal (LC) for the first
      time. Two systems are studied in this work; in the first, the same surfactant is
      used for both the dispersion of the SWNTs and the formation of the LC. In the
      second system, we use different surfactants for the dispersion of SWNTs and LC
      formation. Light microscopy imaging combined with small-angle X-ray scattering
      (SAXS) indicates that the nanotubes (NTs) are well dispersed and aligned along
      the LC director. The macroscopic property, namely, the viscosity, is strongly
      enhanced by the presence of the NTs.

PMID- 16430236
TI  - Oxadiazole-metal interface: from isolated molecules to pi-stacking.
AB  - Derivatives of 2,5-diaryl-1,3,4-oxadiazole are used widely for electron transport
      in organic light emitting diodes (OLED). This study addresses the structure of
      2,5-diphenyl-1,3,4-oxadiazole (PPD) molecules on Cu(111) using scanning tunneling
      microscopy (STM) and density function theory (DFT): at incomplete coverage, PPD
      molecules are found horizontally on the surface; once the surface area is
      insufficient to accommodate all adsorbates in this fashion, a pi-stacked film of
      vertically arranged molecules is formed. In contrast to bulk PPD, in this film,
      the molecules are arranged face-to-face at a separation of square root(3a0) = 4.4
      A as imposed by the substrate interatomic spacing along the [-2 1 1] direction.

PMID- 16430237
TI  - Carbon 1s X-ray photoemission line shape analysis of highly oriented pyrolytic
      graphite: the influence of structural damage on peak asymmetry.
AB  - C 1s XPS spectra of various highly oriented pyrolytic graphite (HOPG) surfaces,
      untreated, as well as those treated by keV Ar+ beam bombardment and low-energy
      O2, N2, Ar, and H2O plasmas, have been systematically studied by comparing two
      XPS peak-fitting procedures. These procedures treat the spectrum as either (1)
      the overlap of several symmetric component peaks or (2) a single asymmetric peak.
      The results indicate that, in the case of HOPG, the asymmetry parameter defining
      the single peak is directly related to the extent of damage to the alternant
      hydrocarbon structure of the HOPG surface, as manifested by its correlation with
      the symmetric peak component due to the damaged HOPG structure.

PMID- 16430232
TI  - A product of ozonolysis of cholesterol alters the biophysical properties of
      phosphatidylethanolamine membranes.
AB  - There is evidence that some products of the reaction of ozone with cholesterol
      contribute to atherosclerosis. One of these compounds is 3beta-hydroxy-5-oxo-5,6
      secocholestan-6-al. We have synthesized this compound and have demonstrated that
      it reacts with phosphatidylethanolamine to form a Schiff base. The 3beta-hydroxy
      5-oxo-5,6-secocholestan-6-al also affects the physical properties of
      phosphatidylethanolamines. We show by both DSC and X-ray diffraction that it
      increases the negative curvature of the membrane. In addition, 3beta-hydroxy-5
      oxo-5,6-secocholestan-6-al causes the lamellar phase to become disorganized,
      resulting in the loss of lamellar periodicity. The chemical and physical
      interactions of 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al with
      phosphatidylethanolamines may contribute to damaging effects of this lipid on
      cell membranes, resulting in pathology.

PMID- 16430238
TI  - Growth of columnar hydrogel colloidal crystals in water-organic solvent mixture.
AB  - A novel emulsion method has been demonstrated to grow columnar hydrogel colloidal
      crystals by mixing an aqueous suspension of poly-N-isopropylacrylamide-co
      allylamine microgels with organic solvent, driven by the coalescence of micelles
      consisting of organic oil droplets coated by many microgels. This method leads to
      microgel colloidal crystals of several centimeters growing from the top to the
      bottom along the gravity direction. Both temperature and polymer concentration
      play critical roles for the formation of columnar crystals. A phase diagram has
      been determined, and it can be used as a guide to selectively grow different
      crystals, including columnar crystals and randomly oriented crystals, and enable
      the coexistence of columnar crystals and randomly oriented crystals.

PMID- 16430239
TI  - Formation of gold-silver nanowires in thin surfactant solution films.
AB  - Thin, long gold/silver nanowires were grown on substrates in thin surfactant
      solution films. This growth process occurred exclusively in thinning aqueous
      films as the water evaporated, and elongated surfactant template structures were
      formed. The nanowire growth depended on the presence of a relatively high
      concentration of silver ions (typical Ag:Au mole ratio of 1:1). Tuning the pH
      value to about 5 in the growth solution was crucial for the nanowire growth.
      Further development of this process may lead to a simple wet chemical technique
      for the fabrication of relatively uniform arrays of metal nanowires on surfaces.

PMID- 16430240
TI  - The kinetics and saturation of reversible adsorption on patterned (heterogeneous)
      surfaces.
AB  - We analytically examine the time-dependent adsorption of analyte (solute) on a
      finite-sized adsorption region as a model for sensors utilizing patterned or
      heterogeneous surfaces. We account for both reversible adsorption (assuming first
      order reaction) and saturation of the adsorption patch that may arise either from
      packing constraints (finite area) or because of a finite number of binding sites
      (ligands). Our main conclusions include the following: (1) Saturation effects,
      due to either finite patch size or finite number of binding sites, become
      significant at extremely short times. (2) Increasing the strength of binding
      between the analyte and the adsorption sites increases the adsorbed amount at
      short times, but, at long times, the mass adsorbed on a weakly binding patch is
      higher than that on a strongly binding one. (3) The sensitivity of detection, as
      defined by the adsorption of the minimal analyte mass required for signaling,
      over a fixed period of time, does not scale as 1/detection time. As a result,
      increasing the time over which adsorption occurs increases sensitivity, but not
      linearly. Sensitivity of detection also increases with increasing patch area and
      initial binding strength.

PMID- 16430241
TI  - Preservation of the biofunctionality of DNA and protein during microfabrication.
AB  - Microfabrication processes, especially in silicon, are not compatible with
      biomolecules. Silicon and metal-based materials having crystalline structures are
      manipulated under harsh conditions with acids, bases, and organic solvents at
      high temperature. In comparison, organic biomolecules such as DNA and proteins
      have complex, three-dimensional structures and are sensitive to denaturation,
      oxidation, hydrolysis, and thermal destruction. Here, we report on the
      integration of DNA and the biotin-binding protein NeutrAvidin into
      microfabrication processes by using a novel approach based on a gold passivation
      mask. Our data show that this passivation method preserves approximately 84% of
      the biofunctionality of DNA and approximately 30% of that of NeutrAvidin under
      harsh process conditions. This novel technology enables the integration of DNA,
      proteins, and potentially other biological molecules into mass scalable
      microfabrication processes for biomedical devices, biochips, biosensors, and
      microelectromechanical systems with biomolecules (BioMEMS).

PMID- 16430242
TI  - Effects of contact force and salt concentration on the unbinding of a DNA duplex
      by force spectroscopy.
AB  - We report that varying the contact force in force spectroscopy results in a
      significant shift in DNA unbinding forces, measured from short oligonucleotides
      using a PicoForce microscope. The contact force between a 30-mer complementary
      DNA-coated probe and surface was varied from 100 pN to 10 nN, resulting in a
      significant shift in the most abundant unbinding force measured between the
      duplex. When contact forces were set at 200 pN or less, which is generally
      considered to be a low contact force region for biomolecular force spectroscopy
      studies, the shift in DNA unbinding forces was significant with changes in
      contact force. The effect of the salt concentration on the DNA unbinding forces
      was also examined for a range of salt concentrations from 5 to 500 mM because the
      presence of salt ions is necessary to facilitate the hybridization process.
      Although an increase in salt concentration resulted in the facilitation of DNA
      multiple binding events during force spectroscopy measurements, no significant
      shift in unbinding forces was observed. Our experiment demonstrates that the wide
      variation in DNA unbinding forces reported in the literature (50-600 pN) for
      short oligonucleotides can be accounted for by the different contact forces used
      and shows little or no effect of the salt concentration used in those studies.
      Furthermore, this study demonstrates the importance of reporting contact forces
      in force spectroscopy measurements for quantitative comparisons between different
      biomolecular systems, especially for noncovalent-type interactions.

PMID- 16430243
TI  - Electrostatic orientation of enzymes on surfaces for ligand screening probed by
      force spectroscopy.
AB  - In this letter, we show that electrostatic immobilization provides a simple but
      effective approach for the immobilization and orientation of carbonic anhydrase
      onto charged surfaces. The enzyme is oriented differently on oppositely charged
      surfaces, with the majority of active sites facing upward on a positively charged
      surface and downward on a negatively charged surface. An array of negatively
      charged microscale surface patterns within a positively charged background was
      prepared by microcontact printing and used as the substrate to immobilize the
      enzymes. This enabled the probing of the enzyme orientations on the two
      differently charged surface regions by force spectroscopy with the same atomic
      force microscopy (AFM) probe modified with a thiolated sulfonamide inhibitor. The
      unbinding forces between the inhibitor tip and the enzyme immobilized on the two
      differently charged surfaces were measured. Two control experiments, blocking of
      the enzyme active site with a competitive inhibitor and removal of the zinc ion
      from the enzyme catalytic center, were employed to distinguish between specific
      and nonspecific interactions and to further verify the differences in enzyme
      orientation. Autocorrelation analysis of the force histograms was carried out to
      evaluate the specific single enzyme-inhibitor interaction force.

PMID- 16430245
TI  - In situ monitoring of structural changes during colloidal self-assembly.
AB  - Reflectance spectroscopy is utilized to monitor structural changes during the
      self-assembly of a monodisperse colloidal system at the meniscus of a sessile
      drop on an inert substrate. Treating the ordered colloidal structure as a
      photonic crystal is equivalent to monitoring the changes in the photonic band gap
      (PBG) as the colloidal system self-assembles heterogeneously into a crystal
      through solvent evaporation in ambient conditions. Using a modified Bragg's law
      model of the photonic crystal, we can trace the structural evolution of the self
      assembling colloidal system. After a certain induction period, a face-centered
      cubic (FCC) structure emerges, albeit with a lattice parameter larger than that
      of a true close-packed structure. This FCC structure is maintained while the
      lattice parameter shrinks continuously with further increase in the colloidal
      concentration due to drying. When the structure reaches a lattice parameter 1.09
      times the size of that of a true close-packed structure, it undergoes an abrupt
      decrease in lattice spacing, apparently similar to those reported for lattice
      distortive martensitic transformations. This abrupt final lattice shrinkage
      agrees well with the estimated Debye screening length of the electric double
      layer of charged colloids and could be the fundamental reason behind the cracking
      commonly seen in colloidal crystals.

PMID- 16430244
TI  - Probing the surface adsorption and photocatalytic degradation of catechols on
      TiO2 by solid-state NMR spectroscopy.
AB  - The local structure of the TiO2 surface modified with electron-donating bidentate
      ligands, such as catechols, has been investigated by solid-state NMR
      spectroscopy. The adsorption and degradation processes of catechols at the TiO2
      surface were observed. The photocatalytic degradation mechanism of catechols at
      the TiO2 surface was interpreted in terms of the interfacial charge recombination
      reaction with conduction band electrons.

PMID- 16430246
TI  - Surface modification of functional self-assembled monolayers on 316L stainless
      steel via lipase catalysis.
AB  - Lipase catalyzed esterification of therapeutic drugs to functional self-assembled
      monolayers (SAMs) on 316L stainless steel (SS) after assembly has been
      demonstrated. SAMs of 16-mercaptohexadecanoic acid (-COOH SAM) and 11-mercapto-1
      undecanol (-OH SAM) were formed on 316L SS, and lipase catalysis was used to
      attach therapeutic drugs, perphenazine and ibuprofen, respectively, on these
      SAMs. The reaction was carried out in toluene at 60 degrees C for 5 h using
      Novozyme-435 as the biocatalyst. The FTIR spectra after surface modification of 
      OH SAMs showed the presence of the C=O stretching bands at 1745 cm(-1), which was
      absent in the FTIR spectra of -OH SAMs. Similarly, the FTIR spectra after the
      reaction of the -COOH SAM with perphenazine showed two peaks in the carbonyl
      region, a peak at 1764 cm(-1), which is the representative peak for the C=O
      stretching for esters. The second peak at 1681 cm(-1) is assigned to the C=O
      stretching of the remaining unreacted terminal COOH. XPS spectra after lipase
      catalysis with ibuprofen showed a photoelectron peak evolving at 288.5 eV which
      arises from the carbon (C=O) of the carboxylic acid of the drug (ibuprofen).
      Similarly for -COOH SAMs, after esterifiation we see a small, photoelectron peak
      evolving at 286.5 eV which corresponds to the C in the methylene groups adjacent
      to the oxygen (C-O), which should evolve only after the esterification of
      perphenazine with the -COOH SAM. Thus, lipase catalysis provides an alternate
      synthetic methodology for surface modification of functional SAMs after assembly.

PMID- 16430247
TI  - Amorphous drug nanosuspensions. 1. Inhibition of Ostwald ripening.
AB  - Amorphous drug nanosuspensions are prone to particle growth due to Ostwald
      ripening. By incorporating a second component of extremely low aqueous
      solubility, Ostwald ripening can be inhibited. These studies indicate that to
      inhibit ripening, the drug/inhibitor mixture (in the particles) must form a
      single phase. The drug/inhibitor mixture can be characterized by the interaction
      parameter chi using the Bragg-Williams theory, in which single phase mixtures are
      obtained for chi < 2. The chi parameter can be calculated from the (crystalline)
      solubility of the drug in the inhibitor, provided the inhibitor is a liquid, and
      the melting entropy and temperature of the drug.

PMID- 16430248
TI  - Amorphous drug nanosuspensions. 2. Experimental determination of bulk monomer
      concentrations.
AB  - A simple turbidimetric method was developed to measure the bulk concentration of
      drug in nanosuspensions. The bulk concentrations measured were in the range from
      1 microM to 1 mM. The accuracy of the method was checked by determination of the
      bulk concentration of crystalline nanosuspensions, i.e., the crystalline
      solubility, which compared favorably to solubilities measured by a conventional
      method. Results obtained for amorphous nanosuspensions agreed with predictions
      using a theory describing the relative solubility between a supercooled liquid
      and a crystal. Further, it was found that the bulk concentration in Ostwald
      ripening inhibited amorphous nanosuspensions and could be lowered by
      incorporation of higher amounts of the inhibitor, in agreement with predictions
      using the Bragg-Williams theory of nonideal solutions.

PMID- 16430249
TI  - Droplet morphologies on particles with macroscopic surface roughness.
AB  - The equilibrium configuration of liquid droplets on the surface of
      macroscopically rough solid particles was determined by numerical simulations
      using the volume-of-fluid (VOF) method. The fractional surface coverage of the
      particle as a function of the droplet size, equilibrium contact angle, and the
      particle surface roughness amplitude and correlation length has been
      systematically investigated. Droplet size and contact angle were found to
      generally have a stronger effect on surface coverage than particle surface
      roughness. Because of droplet coalescence, a relatively large variation in
      surface coverage was observed for any given total liquid volume, particularly for
      larger values of the equilibrium contact angle.

PMID- 16430250
TI  - Effects of nonionic surfactant C12E5 on the cooperative dynamics of water.
AB  - A dielectric relaxation study of binary mixtures of nonionic surfactant C12E5 +
      water has been made as a function of temperature in the isotropic micellar,
      lamellar, and hexagonal regions of the phase diagram. Two dielectric dispersion
      steps were found and could be assigned to the intermolecular cooperative dynamics
      of water at the micellar interface and in the bulk water domains. A quantitative
      analysis is given. The relaxation amplitudes were used to determine effective
      hydration numbers. The activation energies of water relaxation were calculated
      from the relaxation times. The data indicate weaker surfactant-water and water
      water interactions near the micellar interface compared to those of bulk liquid
      water. Further analysis revealed the presence of water clusters large enough to
      show a cooperative relaxation mode even at high surfactant concentrations.
      However, the relaxation time of this mode is larger compared to that of pure
      water. This points out the importance of confinement effects on water dynamics.

PMID- 16430251
TI  - Geminate proton recombination at the surface of SDS and CTAC micelles probed with
      a micelle-anchored anthocyanin.
AB  - The functionalized flavylium salt 6-hexyl-7-hydroxy-4-methyflavylium chloride
      (HHMF) was employed to probe some of the fundamental features of proton transfer
      reactions at the surface of anionic sodium dodecyl sulfate (SDS) and cationic
      hexadecyltrimethylammonium chloride (CTAC) micelles. In contrast to most ordinary
      flavylium salts, HHMF is insoluble in water, but readily incorporates into SDS
      and CTAC micelles. In the ground state, the rate constant for deprotonation of
      the acid form (AH+) of HHMF decreases 100-fold upon going from CTAC (kd = 3.0 x
      10(6) s(-1)) to SDS (kd = 1.4 x 10(4) s(-1)), consistent with the presence of an
      activation barrier for proton transfer in the ground state and reflecting,
      respectively, stabilization or destabilization of the AH+ cation by the micelle.
      Reprotonation of A is diffusion-controlled in both micelles (kp(SDS) = (2.1 x
      10(11))[H+]aq s(-1) and kp(CTAC) = (3.7 x 10(8))[H+]aq s(-1)), the difference
      reflecting the rate of proton entry into the micelles. In the excited singlet
      state, the rate constants for deprotonation of the AH+* form of HHMF are similar
      in the two micelles (2.4 x 10(10) s(-1)), consistent with activationless proton
      transfer. Reprotonation of the excited A is dominated by fast geminate
      recombination of the photogenerated (A*-H+) pair at the micelle surface
      (k(rec)(SDS) = 6.1 x 10(9) s(-1) and k(rec)(CTAC) = 3.4 x 10(10) s(-1)) and the
      net efficiencies of geminate recombination are quite similar in SDS (0.89) and
      CTAC (0.86).

PMID- 16430252
TI  - Controlling dimensions of polymerized micelles: micelle template versus reaction
      conditions.
AB  - The polymerization of elongated micellar structures offers a novel approach to
      the production of high aspect ratio, water-soluble amphiphilic nanoparticles.
      Three different surfactants were synthesized consisting of a cationic surfactant
      of the form (C(X)H(2X+1))trimethylammonium (where X = 14, 16, or 18) and a vinyl
      containing counterion, 4-vinylbenzoate. The resulting polymer-surfactant
      aggregates have been polymerized to produce high aspect ratio nanoparticles which
      are insensitive to changes in solution conditions. The radius of the initial
      template is maintained on polymerization, whereas the template length is not. The
      aggregate radius is varied by changing the length of the surfactant tail, in this
      case producing aggregates with radii of 1.7, 2.0, or 2.4 nm. Variation of the
      initiator decomposition half-life, by means of using different initiators and
      varying temperature, is used to control the aggregate length between 80 and 500
      nm. Through the process discussed here, both the radius and length of the
      aggregates are controlled independently.

PMID- 16430253
TI  - Polymerization of anionic wormlike micelles.
AB  - Polymerizable anionic wormlike micelles are obtained upon mixing the hydrotropic
      salt p-toluidine hydrochloride (PTHC) with the reactive anionic surfactant sodium
      4-(8-methacryloyloxyoctyl)oxybenzene sulfonate (MOBS). Polymerization captures
      the cross-sectional radius of the micelles (approximately 2 nm), induces micellar
      growth, and leads to the formation of a stable single-phase dispersion of
      wormlike micellar polymers. The unpolymerized and polymerized micelles were
      characterized using static and dynamic laser light scattering, small-angle
      neutron scattering, 1H NMR, and stopped-flow light scattering. Stopped-flow light
      scattering was also used to measure the average lifetime of the unpolymerized
      wormlike micelles. A comparison of the average lifetime of unpolymerized wormlike
      micelles with the surfactant monomer propagation rate was used to elucidate the
      mechanism of polymerization. There is a significant correlation between the ratio
      of the average lifetime to the monomer propagation rate and the average
      aggregation number of the polymerized wormlike micelles.

PMID- 16430254
TI  - Impact of reductive cleavage of an intramolecular disulfide bond containing
      cationic gemini surfactant in monolayers and bilayers.
AB  - The properties of a novel disulfide-bond-containing gemini surfactant bis[N,N
      dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide] disulfide (DSP) were
      studied using a Langmuir balance, supported monolayers, differential scanning
      calorimetry, giant vesicles, and LUVs. In 150 mM NaCl the cmc for DSP was 7.5
      microM whereas that of the monomer N,N-dimethyl-N-hexadecyl-N-(2
      mercaptoethyl)ammonium bromide (MSP) was 12.1 microM. Both surfactants exhibited
      single endotherms upon DSC, with peak temperatures Tm at 21.7 and 20.1 degrees C
      for DSP and MSP, respectively. The endotherm for MSP was significantly broader
      indicating less cooperative melting. Both in monolayers and in vesicles reductive
      cleavage of the disulfide bond of DSP could be obtained by glutathione (GSH). For
      Langmuir films of DSP the addition of GSH into the subphase led to a decrease in
      surface pressure pi as well as surface dipole potential psi. Although the
      cleavage by GSH was significantly slower in the presence of a charge saturating
      concentration of DNA, it did not prevent the reaction. The resulting monomers
      detached from supported monolayers, leading to loss of affinity of the surface
      for DNA. Disruption of giant vesicles containing DSP within approximately 30 s
      following a local injection of GSH was observed, revealing membrane
      destabilization.

PMID- 16430255
TI  - Electron density matching as a guide to surfactant design.
AB  - The effectiveness at reducing interfacial tension between water and different
      organic solvents was studied, with 14 structurally different dichain
      sulfosuccinate surfactants. Variations in chemical structure ranged from
      linear/branched alkyl tail groups, to phenyl-tipped tail units, to partially and
      fully fluorinated tails. The solvents n-heptane, toluene, and perfluoroheptane
      were used as example oil phases. Interfacial activity was measured in terms of a
      reduced interfacial tension scale, R(IFT), based on the value in the presence of
      surfactants compared to that for the pure solvent-water interface. Overall
      surfactant chain structure was determined to be the key factor affecting R(IFT).
      Furthermore, a strong correlation was observed between R(IFT) and the electron
      density rho(e) of the different surfactants: with any given oil, the most
      effective surfactants have rho(e) values closest to that for the solvent. For
      example, phenyl-tipped surfactants were shown to be comparatively more effective
      at the interface with an aromatic solvent (toluene) than with an aliphatic n
      alkane (heptane). Furthermore, fluorination of the tail groups decreased
      effectiveness at the hydrocarbon/water interface, which was substantially
      increased at the fluorocarbon/water interface: this too followed the electron
      density-matching pattern. The importance of chain-tip chemical structure was also
      noted, with regard to the introduction of phenyl, CF3-, and H-CF2- terminal
      moieties. For branched alkyl-tailed surfactants, it was found that effectiveness
      could be linked to an empirical "branching factor". The significance of the
      electron density matching of organic solvent and surfactant for the prediction of
      interfacial activities is highlighted, and this concept may prove useful for the
      future design of new high-efficiency surfactants.

PMID- 16430256
TI  - Nanoparticles in solutions of adsorbing polymers: pair interactions, percolation,
      and phase behavior.
AB  - We study the polymer adsorption characteristics, pair-interaction potentials, and
      phase and percolation behavior in nanoparticle-polymer mixtures. We propose a
      "saturable" adsorption model to capture the effect of the finite surface
      saturation capacity for adsorption, and use polymer self-consistent field theory
      in combination with a McMillan-Mayer framework [McMillan, W. G., Jr.; Mayer, J.
      E. J. Chem. Phys. 1945, 13, 276] to compute the pair-interaction potentials. Our
      results demonstrate novel size effects that distinguish the adsorption
      characteristics of nanoparticles from that of larger particles. Specifically, we
      predict that the nanoparticle regime is characterized by a significant adsorbance
      of polymers, albeit distributed predominantly in the form of tails. We also
      demonstrate that an interplay between the surface saturation, polymer-to-particle
      size ratios, and the polymer concentrations governs the overall effective
      interactions between nanoparticles in the presence of an adsorbing polymer. We
      use simple, mean-field models to relate these characteristics to the phase and
      percolation behavior in such systems. Our results show that the percolation
      thresholds for smaller particles are significantly smaller (and, overall,
      correspond only to a few volume percent) compared to that of the larger
      particles. Further, with a decrease in the size of the particles, we also predict
      a considerable increase in the miscibility of the polymer-particle mixtures. Our
      results are qualitatively in accord with many experimental observations in the
      nanoparticle regime.

PMID- 16430257
TI  - Lattice model for the wetting transition of alkanes on aqueous surfactant
      solutions.
AB  - Droplets of alkanes on aqueous solutions of the cationic surfactants C(n)TAB
      (CH3(CH2)(n-1)N+ (CH3)3Br-) exhibit a first-order wetting transition as the
      concentration of the surfactant is increased. A theoretical model is presented in
      which the surface free energy is broken down into a long-range dispersion
      interaction and a short-range interaction described by a 2D lattice gas, taking
      into account the interaction between oil and surfactant molecules. The model
      provides quantitative agreement with the observed wetting transitions and the
      variation in composition of the wetting film with bulk surfactant concentration.
      The behavior of oil drops on large reservoirs of dilute surfactant is discussed.

PMID- 16430258
TI  - Two-stage collapse of unimolecular micelles with double thermoresponsive coronas.
AB  - Phase transition behavior of unimolecular dendritic three-layer nanostructures
      with dual thermoresponsive coronas is studied. Successive reversible addition
      fragmentation transfer (RAFT) polymerizations of N-isopropylacrylamide (NIPAM)
      and 2-(dimethylamino)ethyl methacrylate (DMA) were conducted using fractionated
      fourth-generation hyperbranched polyester (Bolton H40) based macroRAFT agent. At
      lower temperatures (<20 degrees C), dendritic macromolecules H40-poly(N
      isopropylacrylamide)-poly(2-(dimethylamino)ethyl methacrylate) (H40-PNIPAM-PDMA)
      exist as unimolcular core-shell-corona nanostructures with hydrophobic H40 as the
      core, swollen PNIPAM as the inner shell, and swollen PDMA as the corona. PNIPAM
      and PDMA homopolymers undergo phase transitions at their lower critical solution
      temperatures (LCST), which are found to be 32 degrees C for PNIPAM and 40-50
      degrees C for PDMA, respectively. Upon continuously heating through the LCSTs of
      PNIPAM and PDMA, such dendritic unimolecular micelles exhibit two-stage thermally
      induced collapse. This process is reversible with a two-stage reswelling upon
      cooling. Laser light scattering, micro-differential scanning calorimetry, and
      excimer fluorescence measurements are used to investigate the double phase
      transitions.

PMID- 16430259
TI  - Coarse-grained model simulations of mixed-lipid systems: composition and line
      tension of a stabilized bilayer edge.
AB  - Bilayer disks and ribbons composed of a mixture of short- and long-tail
      phospholipids have been studied by molecular dynamics with a coarse-grained
      model. The effects of system composition on the edge structure, composition, and
      line tension were analyzed. Increases in the fraction of short-tail lipids tend
      to decrease the line tension (i.e., stabilize the edge) but not eliminate it. The
      short-tail lipid is generally enriched at the curved rim forming the bilayer
      edge, with an excess of 3 to 4 molecules per nanometer (relative to the bulk),
      but complete segregation was not observed. In all mixtures, a region depleted in
      the short-tail component occurs just before the edge, corresponding to a bulge in
      the bilayer thickness. The bulge and depletion are more prominent as the bilayer
      composition shifts toward a majority of short-tail lipids. In one case, a net
      excess of long-tail lipids at the edge was demonstrated, suggesting that certain
      circumstances give rise to a "segregation inversion" in which the long-tail lipid
      behaves as an edge stabilizer.

PMID- 16430260
TI  - Long-ranged electrostatic repulsion and crystallization of emulsion droplets in
      an ultralow dielectric medium supercritical carbon dioxide.
AB  - Electrostatic repulsion stabilizes micrometer-sized water droplets with spacings
      greater than 10 microm in an ultralow dielectric medium, CO2 (epsilon = 1.5), at
      elevated pressures. The morphology of the water/CO2 emulsion is characterized by
      optical microscopy and laser diffraction as a function of height. The
      counterions, stabilized with a nonionic, highly branched, stubby hydrocarbon
      surfactant, form an extremely thick double layer with a Debye screening length of
      8.9 microm. As a result of the balance between electrostatic repulsion and the
      downward force due to gravity, the droplets formed a hexagonal crystalline
      lattice at the bottom of the high-pressure cell with spacings of over 10 microm.
      The osmotic pressure, calculated by solving the Poisson-Boltzmann equation in the
      framework of the Wigner-Seitz cell model, is in good agreement with that
      determined from the sedimentation profile measured by laser diffraction. Thus,
      the long-ranged stabilization of the emulsion may be attributed to electrostatic
      stabilization. The ability to form new types of colloids in CO2 with
      electrostatic stabilization is beneficial because steric stabilization is often
      unsatisfactory because of poor solvation of the stabilizers.

PMID- 16430262
TI  - Formation of silver nanoparticles at the air-water interface mediated by a
      monolayer of functionalized hyperbranched molecules.
AB  - Nanofibrillar micellar structures formed by the amphiphilic hyperbranched
      molecules within a Langmuir monolayer were utilized as matter for silver
      nanoparticle formation from the ion-containing water subphase. We observed that
      silver nanoparticles were formed within the multifunctional amphiphilic
      hyperbranched molecules. The diameter of nanoparticles varied from 2-4 nm and was
      controlled by the core dimensions and the interfibrillar free surface area.
      Furthermore, upon addition of potassium nitrate to the subphase, the Langmuir
      monolayer templated the nanoparticles' formation along the nanofibrillar
      structures. The suggested mechanism of nanoparticle formation involves the
      oxidation of primary amino groups by silver catalysis facilitated by "caging" of
      silver ions within surface areas dominated by multibranched cores. This system
      provides an example of a one-step process in which hyperbranched molecules with
      outer alkyl tails and compressed amine-hydroxyl cores mediated the formation of
      stable nanoparticles placed along/among/beneath the nanofibrillar micelles.

PMID- 16430261
TI  - Positive microcontact printing with mercaptoalkyloligo(ethylene glycol)s.
AB  - The soft lithographic replication of patterns with a low filling ratio by
      microcontact printing (microCP) is problematic due to the poor mechanical
      stability of common elastomeric stamps. A recently described strategy to avoid
      this problem employs a modified patterning method, positive microcontact printing
      ((+)microCP), in which a stamp with a mechanically more stable inverted relief
      pattern is used. In contrast to conventional negative microCP ((-)microCP), in
      the contact areas a self-assembled monolayer (SAM) is printed of a "positive
      ink", which provides only minor etch protection, whereas the noncontacted areas
      are subsequently covered with a different, etch-resistant SAM, prior to
      development by chemical etching. With the aim to identify novel, highly versatile
      positive inks, the patterning of gold by (+)microCP with
      mercaptoalkyloligo(ethylene glycol)s (MAOEGs), the subsequent adsorption of
      octadecanethiol (ODT), and the final development by wet chemical etching have now
      been studied. A polydisperse mixture of mercaptoundecylocta(ethylene glycol)
      derivatives was found to provide the best patterning results. The surface
      spreading of the positive ink during stamping, the exchange of printed MAOEGs
      with ODT, and the choice of the right etching bath were identified as key
      parameters that influence the achievable pattern resolution and contrast. Due to
      the modular composition of functionalized alkyloligo(ethylene glycol)
      derivatives, (+)microCP with these positive inks has the potential for easy
      adaptation to a variety of materials and development conditions.

PMID- 16430263
TI  - Heteroaggregation in binary mixtures of oppositely charged colloidal particles.
AB  - Heteroaggregation (or heterocoagulation) rate constants have been measured in
      mixtures of well-characterized colloidal particles of opposite charge with
      multiangle static and dynamic light scattering. This technique permits routine
      measurements of absolute heteroaggregation rate constants, also in the presence
      of homoaggregation. Particularly with multiangle dynamic light scattering, one is
      able to estimate absolute heteroaggregation rate constants accurately in the fast
      aggregation regime for the first time. Heteroaggregation rate constants have also
      been measured over a wide range of parameters, for example, ionic strength and
      different surface charge densities. Amidine latex particles, sulfate latex
      particles, and silica particles have been used for these experiments, and they
      were well characterized with respect to their charging and homoaggregation
      behavior. It was shown that heteroaggregation rate constants of oppositely
      charged particles increase slowly with decreasing ionic strength, and provided
      the surface charge is sufficiently large, the rate constant is largely
      independent of the surface charge. These trends can be well described with DLVO
      theory without adjustable parameters.

PMID- 16430264
TI  - Adsorption of alkylthiol-capped gold nanoparticles onto alkylthiol self-assembled
      monolayers: an SPR study.
AB  - The kinetics of alkylthiol-capped gold nanoparticle (RS/Au-NP) adsorption to
      alkylthiol/Au self-assembled monolayers (RS/Au-SAMs) has been studied using SPR
      (surface plasmon resonance) spectroscopy. Variation of the alkylthiol chain
      terminus (CH3, COOH) and solvent (H2O, hexane) provides insight into the relative
      importance of solvation energies (in the context of surface energies) and RS/Au
      NP structure on adsorption kinetics. The kinetics, fitted to the Langmuir kinetic
      model, yield adsorption and desorption rate constants. DeltaG(ads) derived from
      kinetic data are compared to calculated values of work of adhesion (W(adh)),
      derived from the corresponding surface energies. The absence of a deltaG(ads) -
      W(adh) correlation arises because the measured kinetics are not reporting the
      approach to equilibrium and/or because there are factors (i.e., local chain
      packing defects, surface hydration differences, or particle-particle
      interactions) not accounted for in calculated W(adh) values.

PMID- 16430265
TI  - 19F fast magic-angle spinning NMR studies of perfluoroalkanoic acid self
      assembled monolayers.
AB  - The bonding and dynamic properties of perfluoroalkanoic acid self-assembled
      monolayers (SAMs) on zirconia and titania powders were characterized by Fourier
      transform infrared and solid-state 19F magic-angle spinning NMR spectroscopy. The
      perfluoro fatty acids investigated included C(n)F(2n+1)CO2H, n = 7, 13, 15 and
      17. The acids bind to both metal oxides via ionic carboxylate bonds, but complete
      monolayers are only formed on the zirconia. The shift of the CF3 group from -83
      ppm in the bulk state to -85 ppm for the adsorbed monolayers is assigned to CF3
      groups located at the air/monolayer interface. With the exception of the
      perfluorooctanoic acid, 19F spin lattice relaxation measurements indicate that
      the fluorocarbon chains of the adsorbed acids, even in the case of densely packed
      monolayers, are significantly more mobile than those in the bulk state. The
      motions associated with the enhanced mobility of the adsorbed acids are proposed
      to involve reorientations along the long chain axes. No evidence for chain
      melting in the fluorocarbon SAMs is found for temperatures well above the melting
      temperature of the bulk acids.

PMID- 16430266
TI  - Nanodroplets on a planar solid surface: temperature, pressure, and size
      dependence of their density and contact angles.
AB  - The shape and the density of a liquid drop on a planar solid surface, embedded in
      an inert gas at constant temperature and pressure, were examined on the basis of
      a microscopic density functional approach that accounts for the entropic
      (temperature-dependent) and energetic contributions to the free energy of the
      system. Integro-differential equations describing the profile and the density of
      a cylindrical (2D) drop were derived by the variational minimization of the Gibbs
      free energy with respect to both the drop profile and density under the
      assumption of uniform density. The equations were solved numerically using the
      constraint of a constant number of molecules N(l) per unit length of the drop. It
      was shown that for temperatures lower than a certain temperature Tw the free
      energy against density has generally two minima, representing a stable
      equilibrium state and a metastable one. One of those minima is located at a
      density corresponding to the density of a normal liquid, whereas the other one is
      located at a density comparable to the density of the surrounding inert gas. For
      this reason, the latter state of the drop cannot be stable. For T > Tw, the
      minimum corresponding to the liquid state disappears, and no drop can be formed
      on the surface. The temperature Tw depends on N(l) and the external pressure p
      and increases when N(l) and p increase. The true wetting angle theta0 that the
      drop profile makes with the solid surface depends on the parameters
      characterizing the microscopic interactions, the density, and the surface
      densities. If in the thermodynamically stable state absolute value(cos theta0) >
      1, then no drop is formed on the surface. If in that state absolute value(cos
      theta0) < 1, then at any pressure the true contact angle decreases when the
      temperature increases and approaches Tw. However, theta0 does not reach a zero
      value for T < or = Tw but has for T = Tw a discontinuity from a finite to a zero
      value. The true contact angle also depends on the number of molecules in the drop
      and on the external pressure. For all considered values of N(l), p, and
      microscopic parameters of the intermolecular interactions, the density of the
      drop decreases with increasing temperature. The rate of decrease is constant for
      temperatures sufficiently far from Tw and increases when T approaches Tw. At a
      given temperature and pressure, the density of the drop decreases with decreasing
      N(l). For relatively large drops (N(l) approximately = 10(14)-10(20)), the rate
      of decrease is very small, whereas for small droplets (N(l) approximately =
      10(12)) it becomes much larger.

PMID- 16430267
TI  - Kinetic appearance of first-order gas-liquid expanded and liquid expanded-liquid
      condensed phase transitions below the triple point.
AB  - Phase diagram of Gibbs monolayers of mixtures containing n-hexadecyl phosphate (n
      HDP) and L-arginine (L-arg) at a molar ratio of 1:2 has been constructed by
      measuring surface-pressure-time (pi-t) isotherms with film balance and by
      observing monolayer morphology with Brewster angle microscopy (BAM). This phase
      diagram shows a triple point for gas (G), liquid expanded (LE), and liquid
      condensed (LC) phases at around 6.7 degrees C. Above this triple point, a first
      order G-LE phase transition occurring at 0 surface pressure is followed by
      another first-order LE-LC phase transition taking place at a certain higher
      surface pressure that depends upon temperature. The BAM observation supports
      these results. Below the triple point, the pi-t measurements show only one first
      order phase transition that should be G-LC. All of these findings are in
      agreement with the general phase diagram of the spread monolayers. However, the
      BAM observation at a temperature below the triple point shows that the
      thermodynamically allowed G-LC phase transition is, in fact, a combination of the
      G-LE and LE-LC phase transitions. The latter two-phase transitions are separated
      by time and not by the surface pressure, indicating that the G-LC phase
      transition is kinetically separated into these two-phase transitions. The
      position of the LE phase below the triple point in the phase diagram is along the
      phase boundary between the G and LC phases.

PMID- 16430268
TI  - CO adsorption and oxidation at the catalyst-water interface: an investigation by
      attenuated total reflection infrared spectroscopy.
AB  - Adsorption of carbon monoxide and oxidation of preadsorbed carbon monoxide from
      gas and aqueous phases were studied on a platinum catalyst deposited on a ZnSe
      internal reflection element (IRE) using attenuated total reflection infrared (ATR
      IR) spectroscopy. The results of this study convincingly show that it is possible
      to prepare platinum metal layers strongly attached to an IRE, which are stable
      for over 3 days in aqueous-phase experiments. It is shown that ATR-IR
      spectroscopy is a suitable technique to study adsorption and catalytic reactions
      occurring at the interface of a solid catalyst in an aqueous reaction mixture,
      even with an extreme low-surface-area catalyst. Clearly, ATR-IR spectroscopy
      allows for a direct comparison of reactions on a catalytic surface in gas and
      liquid phases on the same sample. CO was found to adsorb both linearly and
      bridged on the platinum metal layer when adsorbed from the gas phase, but only
      linear CO was detected in aqueous solution, although with 5 times higher
      intensity. Oxidation of preadsorbed CO on platinum occurs in both gas phase,
      wetted gas, and aqueous media and was found to be 2 times faster in the aqueous
      phase compared to gas-phase oxidation because of a promoting effect of water.
      Moreover, during oxidation at room temperature, CO2 adsorbed on Pt/ZnSe was
      detected in both gas and aqueous phases.

PMID- 16430269
TI  - Interaction of alcohols and ethers with a-CF(x) films.
AB  - The surfaces of the magnetic data storage hard disks used in computers are coated
      with a thin film of amorphous carbon and a layer of perfluoropolyalkyl ether
      (PFPE) lubricant. Both protect the surface of the magnetic layer from contact
      with the read-write head flying over the disk surface. Although the most commonly
      used carbon films are amorphous hydrogenated carbon, a-CH(x), it has been
      suggested that the thermal properties of amorphous fluorinated carbon films, a
      CF(x), might be superior. This work has probed the interaction of small
      fluorinated ethers and alcohols with the surfaces of a-CF(x) films to understand
      the effects of carbon film fluorination on the interaction of the lubricant with
      its surface. Temperature-programmed desorption was used to measure the desorption
      energies of small fluorocarbons from the a-CF(x) surface and to compare their
      desorption energies with those from the surfaces of a-CH(x) films. These
      measurements reveal that, similarly to a-CH(x) films, a-CF(x) films expose a
      heterogeneous surface on which fluorocarbons adsorb at sites with a range of
      binding energies. The fluorocarbon ethers all have lower heats of adsorption than
      their hydrocarbon counterparts, suggesting that the ethers adsorb by donation of
      electron density from the oxygen lone-pair electrons to sites on the surface.
      Fluorinated alcohols have roughly the same heats of adsorption as their
      hydrocarbon counterparts. There is little significant difference between the
      interactions of fluorinated ethers (or alcohols) with the surfaces of either a
      CF(x) or a-CH(x) films.

PMID- 16430270
TI  - Volume of a nanoscale water bridge.
AB  - Water bridges formed through capillary condensation at nanoscale contacts first
      stretch and then break during contact rupture. Atomic force microscopy (AFM) pull
      off experiments performed in air with hydrophilic tips and samples show that
      stretched nanoscopic water bridges are in mechanical equilibrium with the
      external pull-off force acting at the contact but not in thermodynamic
      equilibrium with the water vapor in air. The experimental findings are explained
      by a theoretical model that considers constant water volume and decrease of water
      meniscus curvature during meniscus stretching. The model predicts that the water
      bridge breakup distance will be roughly equal to the cubic root of the water
      bridge volume. A thermodynamic instability was noticed for large water bridges
      formed at the contact of a blunt AFM tip (curvature radius of 400 nm) with a flat
      sample. In this case, experiments showed rise and stabilization of the volume of
      the water at the contact in about 1 s. For sharp AFM tips (curvature radius below
      50 nm), the experiments indicated that formation of stable water bridges occurs
      in a much shorter time (below 5 ms).

PMID- 16430271
TI  - Multiple hydrogen bonding for reversible polymer surface adhesion.
AB  - Specific and reversible adhesion of a terminal thymine-functionalized polystyrene
      (PS-thymine) was demonstrated for a silicon surface with complementary adenine
      recognition sites. A novel adenine-containing triethoxysilane (ADPTES), which was
      suitable for covalent attachment to silanol containing surfaces, was synthesized
      in one step from adenine and 3-isocyanatopropyl triethoxysilane (IPTES). 1H and
      13C NMR spectroscopy and fast atom bombardment mass spectroscopy confirmed the
      chemical structure, and 29Si NMR spectroscopy indicated the absence of any
      premature hydrolysis of the alkoxysilane derivative. X-ray photoelectron
      spectroscopy (XPS) and water contact angle measurements indicated the attachment
      of PS-thymine to silicon surfaces that were modified with a mixture of ADPTES and
      3-mercaptopropyl triethoxysilane (MPTES). PS-thymine attachment to surfaces that
      were modified with only MPTES was not observed. The exclusive attachment of PS
      thymine to an ADPTES/MPTES-modified surface confirmed hydrogen bonding-mediated
      adenine-thymine association to silicon surfaces containing a sufficiently low
      concentration of adenine recognition sites. Although PS-thymine attachment to the
      ADPTES/MPTES-modified surfaces was insensitive to THF rinsing, the PS-thymine was
      completely removed from the surface upon DMSO rinsing because of the disruption
      of adenine-thymine hydrogen bonding with a more polar aprotic solvent. PS-thymine
      was successfully reattached to the ADPTES/MPTES-modified surface following the
      DMSO rinse, demonstrating the solvato-reversible nature of the adenine-thymine
      association.

PMID- 16430272
TI  - More on the phase diagram of Laponite.
AB  - The phase diagram of a charged colloidal system (Laponite) has been investigated
      by dynamic light scattering in a previously unexplored range of salt and clay
      concentrations. Specifically, the clay weight and salt molar concentrations have
      been varied in the ranges C(w) = 0.004 divided by 0.025 and C(s) = (1 x 10(-3)
      divided by 5 x 10(-3)) M, respectively. As in the case of free salt water samples
      (C(s) approximately = 1 x 10(-4) M), an aging dynamics toward two different
      arrested phases is found in the whole examined C(w) and C(s) range. Moreover a
      transition between these two different regimes is found. It is clear from these
      measurements that a revision of the phase diagram is necessary and a new
      "transition" line between two different arrested states is drawn.

PMID- 16430273
TI  - 2-Dimensional porphyrin self-assemblies at molecular interfaces.
AB  - The heterodimer formed by electrostatic association of zinc(II) meso-tetrakis(N
      methylpyridyl)porphyrin (ZnTMPyP) and zinc(II) meso-tetrakis(p
      sulfonatophenyl)porphyrin (ZnTPPS) exhibits a strong affinity for the interface
      between water and 1,2-dichloroethane (DCE). Surface tension measurements using
      the quasi-elastic light scattering (QELS) technique reveal that the heterodimer
      adsorption can be described in terms of a Langmuir isotherm with standard Gibbs
      energy of adsorption of -45.5 kJ mol(-1). The orientation of the heterodimer
      transition dipole moment, as estimated from light polarization modulated
      reflectance (LPMR), shows a marked dependence on the bulk concentration of
      heterodimer. On the other hand, changes in the Galvani potential difference
      between the two phases have little effect on the heterodimer organization at the
      water/1,2-dichloroethane interface when the surface coverage is close to maximum.
      This behavior suggests that the ZnTPPS-ZnTMPyP heterodimer forms an adsorbed
      layer of aggregated molecules which affects the physical properties of the
      interface. Indeed, capacitance and surface tension measurements reveal that the
      dielectric properties of the water/DCE interface are significantly altered in the
      presence of heterodimer species.

PMID- 16430274
TI  - Adsorption of benzene on graphitized thermal carbon black: reduction of the
      quadrupole moment in the adsorbed phase.
AB  - The performance of intermolecular potential models on the adsorption of benzene
      on graphitized thermal carbon black at various temperatures is investigated. Two
      models contain only dispersive sites, whereas the other two models account
      explicitly for the dispersive and electrostatic sites. Using numerous data in the
      literature on benzene adsorption on graphitized thermal carbon black at various
      temperatures, we have found that the effect of surface mediation on interaction
      between adsorbed benzene molecules must be accounted for to describe correctly
      the adsorption isotherm as well as the isosteric heat. Among the two models with
      partial charges tested, the WSKS model of Wick et al. that has only six
      dispersive sites and three discrete partial charges is better than the very
      expensive all-atom model of Jorgensen and Severance. Adsorbed benzene molecules
      on graphitized thermal carbon black have a complex orientation with respect to
      distance from the surface and also with respect to loading. At low loadings, they
      adopt the parallel configuration relative to the graphene surface, whereas at
      higher loadings (still less than monolayer coverage) some molecules adopt a slant
      orientation to maximize the fluid-fluid interaction. For loadings in the
      multilayer region, the orientation of molecules in the first layer is influenced
      by the presence of molecules in the second layer. The data that are used in this
      article come from the work of Isirikyan and Kiselev, Pierotti and Smallwood,
      Pierce and Ewing, Belyakova, Kiselev, and Kovaleva, and Carrott et al.

PMID- 16430275
TI  - UV polymerization of self-assembled monolayers of a novel diacetylene on silver:
      a spectroscopic analysis by surface plasmon resonance and surface enhanced Raman
      scattering.
AB  - UV polymerization of self-assembled monolayers of a novel carbazolyl-diacetylene
      (CDS9) chemisorbed on silver films was demonstrated by surface plasmon resonance
      (SPR) and surface enhanced Raman scattering (SERS) experiments. SPR tests
      performed during UV exposure permitted one to observe the growth of the
      absorption coefficient, associated with the formation of the polymeric backbone.
      The Raman spectra of polymerized monolayers exhibited the bands associated with
      the C=C stretching modes of the conjugated backbone, typical of the blue and red
      polymeric phases usually present in polydiacetylenes, with a clear predominance
      of the red form. Moreover, the strong surface enhancement of the Raman band
      corresponding to the aromatic C=C stretching modes suggested that carbazolyl
      groups arrange nearly perpendicularly to the metal surface. In contrast, the
      absence of a SERS signal in the region of conjugated C[triple bond]C bond
      stretchings confirmed a polymerization scheme with conjugated triple bonds nearly
      parallel to the plane of the metal.

PMID- 16430276
TI  - Manipulation of micrometer-scale adhesion by tuning nanometer-scale surface
      features.
AB  - This article demonstrates how the adhesion rates of micrometer-scale particles on
      a planar surface can be manipulated by nanometer-scale features on the latter.
      Here, approximately 500-nm-diameter spherical silica particles carrying a
      substantial and relatively uniform negative charge experienced competing
      attractions and repulsions as they approached and attempted to adhere to a
      negative planar silica surface carrying flat 11-nm-diameter patches of
      concentrated positive charge. The average spacing of these patches profoundly
      influenced the particle adhesion. For dense positive patch spacing on the planar
      collector, the particle adhesion was rapid, and the fundamental adhesion kinetics
      were masked by particle transport to the interface. For patch densities
      corresponding to a planar surface with net zero charge, particle adhesion was
      still rapid. Adhesion kinetics were observably reduced for patch spacings
      exceeding 20 nm and become slower with increased patch spacing. Ultimately, above
      a critical or threshold average patch spacing of 32 nm, no particle adhesion
      occurred. The presence of the threshold average patch spacing suggests that more
      than one positive surface patch was needed for particle capture under the
      particular conditions of this study. Furthermore, at the threshold, the length
      scales of the patch spacing and of the interactive surface area between the
      particle and the surface become similar: The concept of adhesion dominated by the
      matching of length scales is reminiscent of pattern recognition, even though the
      patch distribution on the collector is random in this work. Indeed, fluctuations
      play a critical role in these adhesion dynamics, hence the current behavior
      cannot be predicted by a mean field approach.

PMID- 16430277
TI  - Adsorbed layer structure of cationic gemini and corresponding monomeric
      surfactants on mica.
AB  - We report a comprehensive study of the adsorbed layer morphologies of cationic
      gemini surfactants of the type dodecanediyl-alpha,omega-bis(dimethylalkylammonium
      bromide) and their corresponding monomers, dimethyldodecylalkylammonium bromide,
      on mica using atomic force microscopy soft-contact imaging. As in the bulk,
      aggregate curvature of the adsorbed geminis is found to increase with increasing
      spacer length, but the adsorbed aggregate curvature also increases in the
      presence of CsCl and CsBr. The monomeric surfactants exhibit an unexpected
      transition from globular adsorbed aggregates to a bilayer when the alkyl side
      chain reaches butyl, and this transition is also sensitive to added electrolyte.

PMID- 16430278
TI  - Heats of adsorption and adsorption heterogeneity for methane, ethane, and carbon
      dioxide in MCM-41.
AB  - We report the adsorption isotherms and the isosteric heats of adsorption of pure
      methane, ethane, and CO2 and a mixture of methane and CO2 in the periodic
      mesoporous silica MCM-41 using a multicomponent adsorption calorimeter of the
      Tian-Calvet type, looking in particular at the degree of heterogeneity in the
      adsorption of these species. The adsorption of methane and ethane in MCM-41 was
      found to be essentially homogeneous, while the adsorption of pure CO2 and of CO2
      from a CO2/methane mixture was found to be significantly heterogeneous,
      reflecting the electrostatic interactions between CO2 and the adsorbent.

PMID- 16430279
TI  - Gold glyconanoparticles for mimics and measurement of metal ion-mediated
      carbohydrate-carbohydrate interactions.
AB  - To mimic and measure calcium ion-mediated carbohydrate-carbohydrate interactions,
      four lactose derivatives have been synthesized for assembly on gold
      nanoparticles. The series of lactose derivatives varied by the length of the
      thiolated ethylene glycol anchor chain [O(CH2CH2O)(m)CH2CH2SH; where m = 0, 1, 2,
      and 3] used to self-assemble the carbohydrates to the preformed gold
      nanoparticles of ca. 16 nm diameter. Upon addition of calcium ions to the lactose
      stabilized nanoparticles, rapid carbohydrate-carbohydrate interactions were
      visualized and subsequently measured using UV-visible spectrometry and
      transmission electron microscopy (TEM). The nanoparticle aggregates formed via
      metal-mediated carbohydrate-carbohydrate interactions could be readily
      redispersed through the addition of EDTA. Multiple reaggregation and redispersion
      cycles were achieved, confirming that the aggregation process was due to metal
      ion-mediated carbohydrate interactions rather than calcium chelation by residual
      citrate ions on the particle surface. The essential involvement of the lactose
      moiety in Ca2+ complexation was shown by control measurements on related D
      glucose-derivatized nanoparticles, where a significantly reduced aggregation
      response was obtained only at high ion concentrations. Other group 2 metal ions
      with radii larger than that of calcium, viz., barium and strontium, were also
      shown to mediate the aggregation of the lactose-stabilized nanoparticles. The
      induced aggregation of the lactose nanoparticles was determined to be
      quantitatively dependent upon the calcium ion concentration. Furthermore, the
      analytical sensitivity of the calcium-induced aggregation and the linear dynamic
      range were dependent on the length of the ethylene glycol anchor chain. The
      shortest ethylene glycol chain (m = 0) gave the most sensitive response with the
      optimum limit of detection (0.8 mM Ca2+), whereas the longest ethylene glycol
      chain (m = 3) provides a measurement of calcium ion concentration over the
      largest linear dynamic range (10-35 mM Ca2+). This work has shown that the self
      assembled deposition of lactose derivatives on gold nanoparticles provides
      multivalent carbohydrate surfaces that can be used as mimics for the measurement
      of biologically relevant carbohydrate-carbohydrate interactions. Additionally,
      this study has highlighted the importance of the structure and length of the
      ligand that anchors the carbohydrate sugar to the gold particle surface to
      facilitate such carbohydrate interactions and for "tuning" the analytical
      characteristics of bioassays developed using metal nanoparticle technology.

PMID- 16430280
TI  - Phase behavior of mixed Langmuir monolayers from amphiphilic block copolymers and
      an antimicrobial peptide.
AB  - The behavior of binary monolayers from PMOXA-PDMS-PMOXA triblock copolymers and
      alamethicin, an antimicrobial peptide, was investigated in the context of
      formation of novel biocomposite nanostructured materials. The properties of mixed
      monolayers were studied by surface pressure-area isotherms and Brewster angle
      imaging. As reported previously, functionality of alamethicin relies on its
      aggregation properties in lipid mono- and bilayers. This is also the case in
      polymer matrixes, however, here the mixing properties differ from lipid-peptide
      systems due to the polymers' structural specificity. The peptide influence on the
      polymer films is provided in detail for the first time, and supported by the
      compressibility data to asses the elastic properties of such composite membranes.

PMID- 16430281
TI  - One step growth of protein antifouling surfaces: monolayers of poly(ethylene
      oxide) (PEO) derivatives on oxidized and hydrogen-passivated silicon surfaces.
AB  - We compare two routes for creating protein adsorption-resistant self-assembled
      monolayers (SAMs) by chemical modification of silicon surfaces with poly(ethylene
      oxide) (PEO) oligomeric derivatives. The first route involves the assembly of 2
      methyl[(polyethyleneoxy)propyl]trichlorosilane (Cl3SiMPEO) films onto oxidized
      silicon surfaces (OH-SiO(x)) either by a liquid-phase process at room temperature
      or by a gas-phase process at 423 K, producing Si-O-Si bonds between the substrate
      and the organic layer. The second pathway makes use of the assembly of
      poly(ethylene glycol methyl ether) (MPEG) films onto hydrogen-passivated silicon
      surfaces (H-Si) using a liquid-phase process at 353 or 423 K, leading to the
      formation of Si-O-C bonds between the substrate and the organic layer. Structural
      investigation by X-ray reflectometry (XRR) reveals that the thickness and surface
      densities of the grafted PEO monolayers strongly depend on experimental
      conditions such as temperature and grafting time. Atomic force microscopy (AFM)
      shows that very smooth and homogeneous monolayers can be obtained with average
      roughnesses close to those measured on the corresponding bare substrates.
      Finally, the antifouling properties of the modified silicon surfaces were
      evaluated by X-ray photoelectron spectroscopy (XPS), using a membrane protein
      (P.69 antigen) as model protein. Both types of PEO monolayers exhibit excellent
      protein repellency, as soon as the grafting density is equal to or higher than
      1.7 chains/nm2.

PMID- 16430282
TI  - Mode of interaction of amphiphilic alpha-helical peptide with
      phosphatidylcholines at the air-water interface.
AB  - Surface pressure (pi)-, surface potential (deltaV)-, and dipole moment
      (mu(perpendicular))-area (A) isotherms and morphological behavior were examined
      for monolayers of a newly designed 18-mer amphiphilic alpha-helical peptide (Hel
      13-5), DPPC, and DPPC/egg-PC (1:1) and their combinations by the Wilhelmy method,
      ionizing electrode method, fluorescence microscopy (FM), and atomic force
      microscopy (AFM). The newly designed Hel 13-5 showed rapid adsorption into the
      air-liquid interface to form interfacial films such as a SP-B function.
      Regardless of the composition and constituents in their multicomponent system of
      DPPC/egg-PC, the collapse pressure (pi(c); approximately 42 mN m(-1)) was
      constant, implying that Hel 13-5 with the fluid composition of egg-PC is squeezed
      out of Hel 13-5/DPPC/egg-PC monolayers accompanying a two- to three-dimensional
      phase transformation. FM showed that adding a small amount of Hel 13-5 to DPPC
      induced a dispersed pattern of ordered domains with a "moth-eaten" appearance,
      whereas shrinkage of ordered domains in size occurred for the DPPC/egg-PC mixture
      with Hel 13-5. Furthermore, AFM indicated that (i) the intermediate phase was
      formed in pure Hel 13-5 systems between monolayer states and excluded
      nanoparticles, (ii) protrusions necessarily located on DPPC monolayers, and (iii)
      beyond the collapse pressure of Hel 13-5, Hel 13-5 was squeezed out of the system
      into the aqueous subphase. Furthermore, hysteresis curves of these systems nicely
      resemble those of the DPPC/SP-B and DPPC/SP-C mixtures reported before.

PMID- 16430283
TI  - Polyelectrolyte multilayers with a tunable Young's modulus: influence of film
      stiffness on cell adhesion.
AB  - Mechanical properties of model and natural gels have recently been demonstrated
      to play an important role in various cellular processes such as adhesion,
      proliferation, and differentiation, besides events triggered by chemical ligands.
      Understanding the biomaterial/cell interface is particularly important in many
      tissue engineering applications and in implant surgery. One of the final goals
      would be to control cellular processes precisely at the biomaterial surface and
      to guide tissue regeneration. In this work, we investigate the substrate
      mechanical effect on cell adhesion for thin polyelectrolyte multilayer (PEM)
      films, which can be easily deposited on any type of material. The films were
      cross linked by means of a water-soluble carbodiimide (EDC), and the film elastic
      modulus was determined using the AFM nanoindentation technique with a colloidal
      probe. The Young's modulus could be varied over 2 orders of magnitude (from 3 to
      400 kPa) for wet poly(L-lysine)/hyaluronan (PLL/HA) films by changing the EDC
      concentration. The chemical changes upon cross linking were characterized by
      means of Fourier transform infrared spectroscopy (FTIR). We demonstrated that the
      adhesion and spreading of human chondrosarcoma cells directly depend on the
      Young's modulus. These data indicate that, besides the chemical properties of the
      polyelectrolytes, the substrate mechanics of PEM films is an important parameter
      influencing cell adhesion and that PEM offer a new way to prepare thin films of
      tunable mechanical properties with large potential biomedical applications
      including drug release.

PMID- 16430284
TI  - Membrane-mimetic films of asymmetric phosphatidylcholine lipid bolaamphiphiles.
AB  - Membrane-spanning phospholipid bolaamphiphiles either alone or as a constituent
      of a multicomponent lipid membrane may prove to be facile building blocks for
      generating robust bioactive membrane-mimetic assemblies. We have previously
      reported the synthesis of asymmetric dialkyl phospholipid bolaamphiphiles that
      contain ester linked phosphatidylcholine and amine functionalities at opposite
      chain ends. In this report, we describe the synthesis of phospholipid
      bolaamphiphiles that are conjugated to biotin via the terminal amine with or
      without a poly(ethylene oxide) spacer arm of varying chain length. The behavior
      of biotinylated bolaamphiphiles as a self-assembled monolayer at an air-water
      interface was characterized by epi-fluorescence microscopy and revealed that
      domain structure and pi-A isotherms were substantially influenced by linker type
      and size. Substrate bound assemblies were produced by Langmuir-Blodgett
      deposition onto planar substrates coated with an avidin derivatized
      polyelectrolyte multilayer. Significantly, external reflectance infrared
      spectroscopy confirmed the fabrication of bolaamphiphile thin films that display
      extended stability in vitro.

PMID- 16430285
TI  - Smooth model surfaces from lignin derivatives. I. Preparation and
      characterization.
AB  - Lignin model surfaces were prepared from aqueous alkaline solutions by spin
      coating on silica wafers. Films of thicknesses between 20 and 140 nm were easily
      made by variations in the spinning rate or in the lignin concentration. The
      roughnesses of the lignin surfaces were relatively low, approximately 1.1 nm
      (rms) on an area of 25 microm2, as determined by atomic force microscopy imaging.
      The stability of the lignin films in aqueous solutions was found to be excellent.
      No changes in the thickness of model surfaces immersed in slightly alkaline
      solutions (pH 9.2) could be detected even after 5 h soaking. A 10 percent
      reduction in the thickness of the lignin film was observed after 5 h of exposure
      to a solution containing 0.1 M NaCl. This novel preparation method opens great
      possibilities for further fundamental studies, where interactions between lignin
      and other substances are of interest to investigate.

PMID- 16430287
TI  - Hysteresis in clay swelling induced by hydrogen bonding: accurate prediction of
      swelling states.
AB  - We perform grand-canonical molecular simulations to study the molecular mechanism
      of clay swelling hysteresis as a function of the relative humidity. In
      particular, we focus on the transition from the one- to the two-layer hydrate and
      the influence of three types of counterions (Li+, Na+, and K+). Our results cover
      the experimental relative humidity region where swelling and shrinking usually
      occur. We show that the thermodynamic origin of swelling hysteresis is a free
      energy barrier separating the layered hydrates. This free-energy barrier is
      dominated by breaking and formation of hydrogen bonds between and within water
      layers. This network of water molecules is similar for all counterions, but the
      positions of these counterions depend upon their size. The relatively large K+
      counterions show more affinity for clay surface adsorption, which increases the
      free-energy barrier and inhibits swelling. On the other hand, the relatively
      small Li+ counterions are quite well-accommodated in the water network, and
      thereby, they can form a new swelling state with a basal spacing of approximately
      13.5 A. This new swelling state is an alternative explanation for the widely
      accepted simultaneous occurrence of two or more swelling phases.

PMID- 16430286
TI  - Photopolymerization of mixed monolayers and black lipid membranes containing
      gramicidin A and diacetylenic phospholipids.
AB  - We formed monolayers and black lipid membranes (BLMs) of photopolymerizable
      lipids mixed with the channel-forming protein gramicidin A to evaluate their
      miscibility and the potential for improved stability of the BLM scaffold through
      polymerization. Analyses of surface pressure vs area isotherms indicated that
      gramicidin A dispersed with three different synthetic, polymerizable, diacetylene
      containing phospholipids, 1,2-di-10,12-tricosadiynoyl-sn-glycero-3-phosphocholine
      (DTPC), 1,2-di-10,12-tricosadiynoyl-sn-glycero-3-phosphoethanolamine (DTPE), and
      1-palmitoyl-2,10,12-tricosadiynoyl-sn-glycero-3-phosphoethanolamine (PTPE) to
      form mixed monolayers at the air-water interface on a Langmuir-Blodgett (LB)
      trough. Conductance measurements across a diacetylenic lipid-containing BLM
      confirmed dispersion of the gramicidin channel with the lipid layer and
      demonstrated gramicidin ion-channel activity before and after UV exposure.
      Polymerization kinetics of the diacetylenic films were monitored by film pressure
      changes at constant LB trough area and by UV-vis absorption spectroscopy of
      polymerized monolayers deposited onto quartz. An initial increase in film
      pressure of both the pure diacetylene lipid monolayers and mixed films upon
      exposure to UV light indicated a change in the film structure. Over the time
      scale of the pressure increase, an absorbance peak indicative of polymerization
      evolved, suggesting that the structural change in the lipid monolayer was due to
      polymerization. Film pressure and absorbance kinetics also revealed degradation
      of the polymerized chains at long exposure times, indicating an optimum time of
      UV irradiation for maximized polymerization in the lipid layer. Accordingly,
      exposure of polymerizable lipid-containing black lipid membranes to short
      increments of UV light led to an increase in the bilayer lifetime.

PMID- 16430288
TI  - Raman spectroscopic investigation of gas interactions with an aligned multiwalled
      carbon nanotube membrane.
AB  - Raman spectroscopy has been used to investigate ethane, propane, and SF6
      interactions with an aligned multiwalled carbon nanotube (MWNT) membrane.
      Pressures of 7.5-9.3 atm and temperatures of 293-333 K were examined for propane
      and SF6, whereas slightly lower temperatures (263-293 K) and pressures (6.7-7.5
      atm) were used for ethane. Red-shifting and broadening is seen for the C-C
      stretching vibrations of the two hydrocarbons, as well as for the A1g symmetric
      vibration (nu1) of SF6. These spectral features indicate that the interaction
      between the gas and the nanotube membrane is capable of perturbing molecular
      vibrations and creating red-shifted features. Control experiments done on
      polycrystalline graphite and a polystyrene blank indicate that this spectral
      behavior is unique to gases interacting with the nanotubes in the membrane.

PMID- 16430289
TI  - Size effects on miscibility and glass transition temperature of binary polymer
      blend films.
AB  - After determining the size dependent miscibility of binary polymer blend films
      using molecular dynamics simulation and thermodynamics, the size dependent glass
      transition temperatures Tg(w,D) of several polymer blend films in miscible ranges
      are determined by computer simulation and the Fox equation where w is the weight
      fraction of the second component and D denotes thickness of films. The Tg(w,D)
      function of a thin film can decrease or increase as D decreases depending on
      their surface or interface states. The computer simulation results are consistent
      with available experimental results and theoretical results for polymer blend
      films of PPO/PS [poly(2,6-dimethyl-1,4-phenylene oxide)/polystyrene] and
      stereoregular PMMA/PEO [poly(methyl methacrylate)/poly(ethylene oxide)]. The
      physical background of the above results is related to the root of mean square
      displacement of thin films in their different regions.

PMID- 16430290
TI  - Directed assembly of surface-supported bilayers with transmembrane helices.
AB  - The lateral assembly of transmembrane (TM) helices gives rise to membrane
      proteins with complex folds, which play important roles in biochemical processes.
      Therefore, the assembly of surface-supported bilayers containing TM helices is
      the first step toward the development of functional biomembrane mimetics. Here we
      report novel directed assembly of surface-supported lipid bilayers with laterally
      mobile TM helices. The TM helices were incorporated into lipid monolayers at the
      air/water interface, and the monolayers were then transferred onto glass
      substrates using Langmuir-Blodgett (LB) deposition. Finally, bilayers were
      assembled using lipid vesicle fusion on top of the LB monolayers. The novelty is
      the incorporation of the peptides into the monolayer at the first step of bilayer
      assembly, which allows control over the peptide concentration and orientation.
      The transmembrane orientation of the peptides was confirmed using oriented
      circular dichroism (OCD), lateral mobility was assessed using fluorescence
      recovery after photobleaching (FRAP), and diffusion coefficients were determined
      using a novel boundary profile evolution (BPE) method. The described directed
      assembly approach can be used to develop versatile bilayer platforms for studying
      membrane proteins interactions in native bilayer environments.

PMID- 16430291
TI  - Flow-enhanced epitaxial ordering of brush-like macromolecules on graphite.
AB  - Long-range orientational order in monolayers of brush-like macromolecules was
      achieved during spreading of a polymer melt on the surface of highly oriented
      pyrolytic graphite. The combination of wetting-induced flow and epitaxial
      adsorption of poly(n-butylacrylate) side chains on graphite led to the formation
      of large domains of uniaxially oriented rodlike molecules. The domain size varied
      from ca. 1 to 10 microm which is noticeably larger than the submicrometer-sized
      mosaic domains typically observed upon adsorption from solution. The increase in
      the degree of order is attributed to the flow-enhanced diffusion of the
      macromolecules within spreading monolayers which facilitates the epitaxial
      alignment of the large macromolecules. The diffusion coefficient was shown to
      increase linearly with the spreading rate. Even though the ordering occurred
      during flow, no correlation was observed between the molecular orientation and
      the flow direction. Thus, the role of the flow was not to induce the molecular
      orientation but to facilitate the intrinsic ordering process. This finding can
      inspire and lead to new strategies for constructing large scale ordered
      structures on surfaces.

PMID- 16430292
TI  - Application of porous phosphate heterostructure materials for gas separation.
AB  - In this study, the adsorbents Cu+-3SiPPH723 and Cu2+-3SiPPH723 were prepared
      starting from a silica-expanded zirconium phosphate heterostructure, 3SiPPH(0.2),
      which was subjected to an ion exchange with Cu(I) and Cu(II). These materials
      were characterized using powder X-ray diffraction, X-ray photoelectron
      spectroscopy, ammonia thermally programmed desorption, hydrogen temperature
      programmed reduction, and N2 adsorption (77 K). The equilibria and kinetics of
      adsorption of pure propylene (C3H6) and propane (C3H8) were studied using a
      conventional glass high-vacuum volumetric device, equipped with grease-free
      valves, in the temperature range of 273-393 K. The starting material,
      3SiPPH(0.2), presented a high acidity and irreversible chemisorption of the
      olefin, which increases with temperature. Unlike the support, the irreversible
      adsorption of the olefin on the Cu+-3SiPPH723 and Cu2+-3SiPPH723 samples
      decreases with increasing temperature and disappears at 393 K, showing a very
      high selectivity toward propylene. The C3H8 adsorption in all the samples was
      always reversible. On the basis of the results of this study, both Cu+-3SiPPH723
      and Cu2+-3SiPPH723 samples can be efficiently applied in the separation of a
      C3H6/C3H8 mixture at 393 K. Cu+-3SiPPH723 would have the highest efficiency,
      because its capacity for C3H6 adsorption was higher than that for the Cu2+
      3SiPPH723 sample.

PMID- 16430293
TI  - Close-packed colloidal crystalline arrays composed of silica spheres coated with
      titania.
AB  - Titania coated monodisperse silica spheres have been synthesized and fabricated
      as a close-packed colloidal crystalline array. We have demonstrated that the
      coated colloidal sphere can be used to control the peak position of the optical
      stop band through variation of the coating thickness. The titania coated silica
      spheres were prepared by the layer-by-layer assembly coating process, which
      reciprocally laminates the cationic polyelectrolyte and the anionic titania
      nanosheets on a monodisperse silica spheres, and were sintered to change the
      titania nanosheets to anatase. The Bragg diffraction peak of the colloidal
      crystalline array shifted to the long wavelength region with an increase of
      thickness of the titania layer. Angle-resolved reflection spectra measurements
      clarified that the red shift was caused by increasing of the refractive index
      with increase of the thickness of the layer. The current work suggests new
      possibilities for the creation of advanced colloidal crystalline arrays with
      tunable optical properties from tailored colloidal spheres.

PMID- 16430294
TI  - Effect of high salt concentrations on the stabilization of bubbles by silica
      particles.
AB  - The stabilization of air bubbles by hydrophobically modified silica particles has
      been investigated in detail. The silica particles used had a nominal primary
      particle size of 20 nm and were made hydrophobic by treatment with
      dichlorodimethylsilane to yield particles with varying percent grafting of alkyl
      chains ("% SiOR"). Contact-angle (theta) measurements of pure water droplets on
      flats made from compressed samples of the particles showed a steep increase in
      theta above ca. 20% SiOR. Other measurements also showed a significant increase
      in theta when the salt concentration was raised to 1-3 mol dm(-3). Bubbles were
      formed in a sonicated dispersion of particles by suddenly lowering the pressure.
      Maximum stability was obtained with 33% SiOR particles and 2-3 mol dm(-3) NaCl.
      Under these conditions, theta was around 40 degrees. Above a threshold size of
      around 70 microm, bubbles were extremely stable to disproportionation and
      coalescence and bubble stability increased significantly with an increase in the
      NaCl concentration from 0.5 to 3 mol dm(-3). Furthermore, rheological
      measurements showed that at NaCl concentrations in this range weak particle gels
      were formed with a finite yield stress. The strength of these gels increased with
      an increasing NaCl concentration between 0.5 and 3 mol dm(-3) and with an
      increasing time of aging the dispersions, implicating this as part of the
      mechanism leading to an increased bubble stability in these systems. Dispersions
      in the absence of NaCl showed little or no foamability at all. Use of CaCl2 and
      Al(NO)3 at similar ionic strengths showed that equivalent stability could not be
      obtained with these salts. Atomic force microscopy (AFM) measurements of the
      adhesion between a pure (0% SiOR) silica sphere and flat showed a significant
      increase in the adhesion between 0.5 and 3 mol dm(-3) NaCl, even though in this
      concentration range no significant change in the electrostatic repulsion might be
      expected. It is concluded that the increased particle-particle adhesion,
      effective hydrophobicity, and bubble-stabilization properties of the particles at
      high NaCl concentrations are probably due to the collapse of protruding
      polysilicic acid chains on the surface of the silica.

PMID- 16430295
TI  - Well-defined nanoparticles formed by hydrophobic assembly of a short and
      polydisperse random terpolymer, amphipol A8-35.
AB  - Amphipols are short amphilic polymers designed for applications in membrane
      biochemistry and biophysics and used, in particular, to stabilize membrane
      proteins in aqueous solutions. Amphipol A8-35 was obtained by modification of a
      short-chain parent polymer (poly(acrylic acid); PAA) with octyl- and
      isopropylamine, to yield an amphiphilic product with an average molar mass of 9
      10 kg x mol(-1) (sodium salt form) and a polydispersity index of 2.0 to 3.1,
      depending on the source of PAA. The behavior of A8-35 in aqueous buffers was
      studied by size exclusion chromatography, static and dynamic light scattering,
      equilibrium and sedimentation velocity analytical ultracentrifugation, and small
      angle neutron scattering. Despite the variable length of the chains and the
      random distribution of hydrophobic groups along them, A8-35 self-organizes into
      well-defined assemblies. The data are best compatible with most of the polymer
      forming compact assemblies (particles) with a molar mass of approximately 40 kg x
      mol(-1), a radius of gyration of approximately 2.4 nm, and a Stokes radius of
      approximately 3.15 nm. Each particle contains, on average, four A8-35
      macromolecules and 75-80 octyl chains. Neutron scattering reveals a sharp
      interface between the particles and water. A minor (approximately 0.1%) mass
      fraction of the material forms much larger aggregates, whose proportion may
      increase under certain conditions of preparation or handling, such as low pH.
      They can be removed by gel filtration.

PMID- 16430296
TI  - Phase behavior of mixtures of oppositely charged nanoparticles: heterogeneous
      Poisson-Boltzmann cell model applied to lysozyme and succinylated lysozyme.
AB  - We study the phase behavior of mixtures of oppositely charged nanoparticles, both
      theoretically and experimentally. As an experimental model system we consider
      mixtures of lysozyme and lysozyme that has been chemically modified in such a way
      that its charge is nearly equal in magnitude but opposite in sign to that of
      unmodified lysozyme. We observe reversible macroscopic phase separation that is
      sensitive not only to protein concentration and ionic strength, but also to
      temperature. We introduce a heterogeneous Poisson-Boltzmann cell model that
      generally applies to mixtures of oppositely charged nanoparticles. To account for
      the phase behavior of our experimental model system, in addition to steric and
      electrostatic interactions, we need to include a temperature-dependent short
      ranged interaction between the lysozyme molecules, the exact origin of which is
      unknown. The strength and temperature dependence of the short-ranged attraction
      is found to be of the same order of magnitude as that between unmodified lysozyme
      molecules. The presence of a rather strong short-ranged attraction in our model
      system precludes the formation of colloidal liquid phases (or complex
      coacervates) such as those typically found in mixtures of globular protein
      molecules and oppositely charged polyelectrolytes.

PMID- 16430297
TI  - Association behavior of mixed triblock copoly(oxyalkylene)s (type EBE and ESE) in
      aqueous solution.
AB  - The micellization of binary mixtures of water-soluble block copolymers
      E(m)B(n)E(m) and E(m)S(n)E(m) in dilute solution was investigated by light
      scattering methods. We use the notation E, B, and S to denote chain units
      derived, respectively, from ethylene oxide, butylene oxide, and styrene oxide and
      the subscripts to denote number-average chain lengths in chain units. Two
      distinct distributions of micelles were formed in solutions of a 50:50 wt %
      mixture of copolymers E64B20E64 and E137S18E137, which had hydrophobic blocks of
      similar length but very different hydrophobicity. One distribution of micelles
      was formed in solutions of a mixture (50:50 wt %) of copolymers E135B20E135 and
      E82S9E82, which had hydrophobic blocks of different length but similar
      hydrophobicity. In this case, the properties of the micelles formed in solutions
      of the mixture were very similar to those of micelles of E82S9E82 alone. This
      result extended to concentrated solutions, because the hard-gel boundary for the
      mixture proved to be very similar to that of solutions of E82S9E82 alone.

PMID- 16430298
TI  - Controlled synthesis of Ag/TiO2 core-shell nanowires with smooth and bristled
      surfaces via a one-step solution route.
AB  - Ag/TiO2 core-shell nanowires were synthesized via a one-step solution method
      without using a template. Interestingly, the shell morphologies can be controlled
      to be smooth or bristled by altering the reaction temperature. Moreover, the TiO2
      shell thickness and bristle length can be tuned by changing the AgNO3
      concentration. Scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), high-resolution transmission electron microscopy (HRTEM),
      selected-area electron diffraction (SAED), energy-dispersive X-ray analysis
      (EDS), X-ray powder diffraction (XRD), and X-ray photoelectron spectroscopy (XPS)
      were used to characterize the resultant Ag/TiO2 core-shell nanowires. Moreover,
      the absorption peaks of our samples are significantly red-shifted compared with
      those of the uncoated pure silver nanowires, indicating that interaction between
      the core and shell occurred. On the basis of the experimental results, we
      proposed a template-induced Oswald ripening mechanism to explain the formation of
      the Ag/TiO2 core-shell nanowires.

PMID- 16430299
TI  - Thermal and chemical stability of diphenylalanine peptide nanotubes: implications
      for nanotechnological applications.
AB  - The diphenylalanine peptide, the core recognition motif of the beta-amyloid
      polypeptide, efficiently self-assembles into discrete, well-ordered nanotubes.
      Here, we describe the notable thermal and chemical stability of these tubular
      structures both in aqueous solution and under dry conditions. Scanning and
      transmission electron microscopy (SEM and TEM) as well as atomic force microscopy
      (AFM) revealed the stability of the nanotubes in aqueous solution at temperatures
      above the boiling point of water upon autoclave treatment. The nanotubes
      preserved their secondary structure at temperatures up to 90 degrees C, as shown
      by circular dichroism (CD) spectra. Cold field emission gun (CFEG) high
      resolution scanning electron microscope (HRSEM) and thermogravimetric analysis
      (TGA) of the peptide nanotubes after dry heat revealed durability at higher
      temperature. It was shown that the thermal stability of diphenylalanine peptide
      nanotubes is significantly higher than that of a nonassembling dipeptide,
      dialanine. In addition to thermal stability, the peptide nanotubes were
      chemically stable in organic solvents such as ethanol, methanol, 2-propanol,
      acetone, and acetonitrile, as shown by SEM analysis. Moreover, the acetone
      environment enabled AFM imaging of the nanotubes in solution. The significant
      thermal and chemical stability of the peptide nanotubes demonstrated here points
      toward their possible use in conventional microelectronic and
      microelectromechanics processes and fabrication into functional nanotechnological
      devices.

PMID- 16430300
TI  - Structure and nanomechanical characterization of electrospun PS/clay
      nanocomposite fibers.
AB  - Electrospinning has been emerging as one of the most efficient methods to
      fabricate polymer nanofibers. In this paper, PS/clay nanocomposite fibers with
      varying diameters were electrospun onto solid substrates. The fiber diameters
      were adjusted from 4 microm to 150 nm by changing the solution concentration.
      Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      atomic force microscopy (AFM) were used to characterize the fiber morphology.
      Shear modulation force microscopy (SMFM) was utilized to investigate the surface
      nanomechanical properties of electrospun fibers as a function of the fiber
      diameter and temperature. In the absence of clay, no change in T(g) was observed,
      even though a large increase of shear modulus below the glass transition
      temperature was found. This effect was postulated to result from the molecular
      chain alignment during electrospinning. The addition of functionalized clays to
      the spinning solution produced fibers with a highly aligned montmorillonite layer
      structure at a clay concentration of 4 wt %. Clay agglomerates were observed at
      higher concentrations. The existence of clay further enhanced the shear modulus
      of fibers and increased the glass transition temperature by nearly 20 degrees C.

PMID- 16430301
TI  - Solution-phase synthesis of spherical zinc sulfide nanostructures.
AB  - A facile solution-phase method has been developed to synthesize specially hollow
      and solid ZnS nanospheres. High-resolution TEM images on the nanospheres suggest
      their formation via the oriented aggregation of the primary ZnS nanocrystals. The
      morphology and size of the ZnS nanospheres can also be tuned easily by
      controlling the experimental conditions. These special spherical structures are
      very easily encapsulated within a uniform silica layer without any surface
      modification, suggesting potential applications in biochemistry and
      biodiagnostics.

PMID- 16430302
TI  - Numerical study of a drug release profile in the transdermal drug delivery
      system.
AB  - Drug release by diffusion from an unstressed thin polymer film with a dissolved
      crystallizable component was simulated using a kinetic Monte Carlo model. This
      model was used previously to study Ostwald ripening in a high crystallizable
      component regime and was shown to correctly simulate solvation, diffusion, and
      precipitation. In this study, the same model with modifications was applied to
      the drug transportation and release in the low concentration regime of interest
      to the transdermal drug delivery system (TDS) community. We demonstrate the
      model's utility by simulating diffusion, crystal precipitation, growth and
      shrinkage during storage, and drug release from the thin TDS to a surface under
      different conditions. The simulation results provide a first approximation for
      the drug release profile occurring from TDS to skin. It has been reported that
      growth of drug crystals in TDS occurs mainly in the middle third of the polymer
      layer at relatively higher temperatures. The results from the simulations showed
      that the release rate and concentration profile of a TDS depend on the
      dissolution process of the crystal. At low storage temperature, the drug
      precipitates to form small evenly distributed crystals throughout the thickness
      of the TDS patch. The release rate of these small, evenly distributed crystals
      most closely matched that of a completely dissolved drug.

PMID- 16430303
TI  - Impedance spectroscopy of OmpF porin reconstituted into a mercury-supported lipid
      bilayer.
AB  - The channel-forming protein OmpF porin was incorporated in a biomimetic membrane
      consisting of a lipid bilayer tethered to a mercury electrode via a thiolipid,
      and it was investigated in aqueous KCl by electrochemical impedance spectroscopy.
      The impedance spectra, recorded from 1 x 10(-2) to 1 x 10(5) Hz over a potential
      range of 0.7 V, were fitted to an equivalent circuit consisting of four RC
      meshes. The dependence of the resulting circuit elements upon the applied
      potential was interpreted on the basis of a general approximate approach based on
      a model of the electrified interphase and on the kinetics of the translocation of
      potassium and chloride ions across the lipid bilayer, assisted by the OmpF porin.

PMID- 16430304
TI  - Analysis of electron transfer processes across liquid/liquid interfaces:
      estimation of free energy of activation using diffuse boundary model.
AB  - The evaluation of the free energy of activation pertaining to the electron
      transfer reactions occurring at liquid/liquid interfaces is carried out employing
      a diffuse boundary model. The interfacial solvation numbers are estimated using a
      lattice gas model under the quasichemical approximation. The standard reduction
      potentials of the redox couples, appropriate inner potential differences,
      dielectric permittivities, as well as the width of the interface are included in
      the analysis. The methodology is applied to the reaction between [Fe(CN)6](3-/4-)
      and [Lu(biphthalocyanine)](3+/4+) at water/1,2-dichloroethane interface. The rate
      determining step is inferred from the estimated free energy of activation for the
      constituent processes. The results indicate that the solvent shielding effect and
      the desolvation of the reactants at the interface play a central role in
      dictating the free energy of activation. The heterogeneous electron-transfer rate
      constant is evaluated from the molar reaction volume and the frequency factor.

PMID- 16430305
TI  - Modulating the pattern quality of micropatterned multilayer films prepared by
      layer-by-layer self-assembly.
AB  - Patterned multilayer films composed of poly(allylamine hydrochloride) (PAH) and
      poly(sodium 4-styrenesulfonate) (PSS) were prepared using dip and spin self
      assembly (SA) methods. A silicon substrate was patterned with a photoresist thin
      film using conventional photolithography, and PAH/PSS multilayers were then
      deposited onto the substrate surface using dip or spin SA. For spin SA, the
      photoresist on the substrate was retained, despite the high centrifugal forces
      involved in depositing the polyelectrolytes (PEs). The patterned multilayer films
      were formed by immersing the PE-coated substrates in acetone for 10 min. The
      effect of ionic strength on the pattern quality in dip and spin multilayer
      patterns (line-edge definition and surface roughness of the patterned region) was
      investigated by increasing the salt concentration in the PE solution (range 0-1
      M). In dip multilayer patterns, the presence of salt increased the film surface
      roughness and pattern thickness without any deformation of pattern shape. The
      spin multilayer patterns formed without salt induced a height profile of about
      130 nm at the pattern edge, whereas the patterns formed with high salt content (1
      M) were extensively washed off the substrates. Well-defined pattern shapes of
      spin SA multilayers were obtained at an ionic strength of 0.4 M NaCl. Multilayer
      patterns prepared using spin SA and lift-off methods at the same ionic strength
      had a surface roughness of about 2 nm, and those prepared using the dip SA and
      lift-off method had a surface roughness of about 5 nm. The same process was used
      to prepare well-defined patterns of organic/metallic multilayer films consisting
      of PE and gold nanoparticles. The spin SA process yielded patterned multilayer
      films with various lengths and shapes.

PMID- 16430306
TI  - Photonic rubber sheets with tunable color by elastic deformation.
AB  - This article describes an elastic silicone sheet with reversible tuning
      structural color. The sheet has a thin layer of cubic close-packed, ccp,
      colloidal particles embedded in poly(dimethylsiloxane), PDMS, elastomer. The
      array of ccp (111) planes diffracts light of selective wavelengths according to
      Bragg's law. This is responsible for the structural color of the PDMS sheet.
      Because the sheet was stretched in the horizontal direction, it was reduced in
      size in the vertical direction. As a result, the lattice distance of ccp (111)
      planes decreased, and the reflected wavelength of light shifted to shorter
      wavelengths. For example, the peak of reflection was tuned from 589 to 563 nm as
      a function of sheet elongation. The peak position decreased linearly with
      deformation when the deformation was within 20% of its elongation. Accordingly,
      the color of the PDMS sheet changed from red to green. When the mechanical strain
      on the PDMS sheet was released, the peak returned to its original position, and
      the color of the PDMS sheet also changed back to red. Tuning the color of the
      PDMS sheet is a reversible and repeatable process. The novel PDMS sheet has the
      potential to be applied to mechanical strain sensing.

PMID- 16430307
TI  - Humidity-sensing inverse opal hydrogels.
AB  - Soft material hydrogel sensors have seen increased interest recently. Most of
      these sensors are used in an aqueous environment. In this study, we depart from
      this trend and analyze the ability of a periodic hydrogel structure to respond to
      variations in ambient humidity through an optical change. First, a polyacrylamide
      inverse opal hydrogel structure was created from a colloidal crystal template.
      Next, this material was tested under various humidity conditions and responded to
      these changes by shifting its optical reflection peak noticeably within the
      visible wavelength range. This effect opens the doors for these materials as
      humidity sensors. The kinetics of the peak shifts was also observed, showing a
      rapid response to ambient humidity changes. Finally, the structural dimension
      change is compared through peak shifts, Fabry-Perot fringes of the optical
      cavity, and scanning electron microscopy observations.

PMID- 16430308
TI  - Prediction of cytochrome p450-mediated hepatic drug clearance in neonates,
      infants and children : how accurate are available scaling methods?
AB  - Correct dosing of drugs in neonates, infants and children is hampered by a
      general lack of knowledge about drug disposition in this population. Suggested
      methods to improve our knowledge without performing conventional full-scale
      investigations include population pharmacokinetic studies, allometric scaling of
      drug disposition according to bodyweight and in silico prediction of
      pharmacokinetics. The last method entails scaling of pharmacokinetic parameters
      according to age-dependent changes in drug absorption and elimination capacity,
      plasma protein binding and physiological characteristics of the subjects.
      Maturation (or ontogeny) of the drug-metabolising part of the cytochrome P450
      (CYP) enzyme system is thus an important factor in the calculations for most
      drugs. The aim of this commentary is to test and critically examine the proposed
      methods to estimate hepatic clearance (CL) as a function of age (0-20 years),
      with CYP3A-mediated metabolism as the case in point. Midazolam and alfentanil
      were used as model drugs. Allometric scaling failed to predict the CL of
      midazolam and alfentanil in neonates. Calculations using in vitro findings on CYP
      maturation gave better estimates for neonates but very divergent ones for older
      infants and children. This was chiefly due to very different data on CYP3A4/5
      ontogeny in three published studies. In the age range where full adult CYP
      activity per gram of liver could be assumed, allometric scaling and in silico
      predictions gave similar results. These predictions were also in approximate
      agreement with clinical data.The findings with the two model drugs can very
      probably be generalised to most drugs cleared by CYP-dependent hepatic
      metabolism. Allometric scaling accounts for development of body size and function
      but not for the fact that the drug-metabolising capacity of the liver is
      generally low at birth. The crucial question in the prediction of CL is thus when
      the activity of the applicable CYP isoform(s) attains adult levels. There are
      still not enough data on this, particularly when different studies even on the
      same CYP isoform have given very divergent results. It may also be pointed out
      that CYP ontogeny is an area where we have at least some information. There are
      several other important developmental changes about which we know practically
      nothing. Thus, while allometric scaling is generally unreliable for prediction in
      neonates and infants, the alternative method of in silico prediction can at
      present be used only to obtain tentative initial estimates of drug CL. Neither of
      the methods can be used as a substitute for actual clinical studies.

PMID- 16430309
TI  - Significance of the minor cytochrome P450 3A isoforms.
AB  - Cytochrome P450 (CYP) 3A4 is responsible for most CYP3A-mediated drug metabolism
      but the minor isoforms CYP3A5, CYP3A7 and CYP3A43 also contribute. CYP3A5 is the
      best studied of the minor CYP3A isoforms. It is well established that only
      approximately 20% of livers express CYP3A5. The most common reason for the
      absence of expression is a splice site mutation. The frequency of variant alleles
      shows interethnic differences, with the wild-type CYP3A5*1 allele more common in
      Africans than Caucasians and Asians. In individuals who express CYP3A5, the
      percentage contributed to total hepatic CYP3A by this isoform is still unclear,
      with estimates ranging from 17% to 50%. CYP3A5 is also expressed in a range of
      extrahepatic tissues. Only limited information is available on the regulation of
      CYP3A5 expression but it appears to be inducible via the glucocorticoid receptor,
      pregnane X receptor and constitutive androstane receptor-beta, as for CYP3A4.
      Although information on the substrate specificity of CYP3A5 is limited compared
      with CYP3A4, there have been a number of recent pharmacokinetic studies on a
      small range of substrates in individuals of known genotype to investigate the
      contribution of CYP3A5. In the case of midazolam, ciclosporin, nifedipine and
      docetaxel, clearance by individuals with a CYP3A5-expressing genotype did not
      differ from that for nonexpressors, but in the case of tacrolimus, eight
      independent studies have demonstrated faster clearance by those carrying one or
      two CYP3A5*1 alleles. This may reflect faster turnover of tacrolimus by CYP3A5
      than the other substrates. CYP3A5 genotype may affect cancer susceptibility.
      Certain combined CYP3A4/CYP3A5 haplotypes show differential susceptibility to
      prostate cancer and there is a nonsignificant increase in the risk of small-cell
      lung cancer for a CYP3A5*1/*1 genotype. Females positive for CYP3A5*1 appear to
      reach puberty earlier, which may affect breast cancer risk. CYP3A5*1 homozygotes
      may have higher systolic blood pressure.CYP3A7 is predominantly expressed in
      fetal liver but is also found in some adult livers and extrahepatically. The
      molecular basis for expression in adult liver relates to upstream polymorphisms,
      which appear to increase homology to CYP3A4 and make regulation of expression
      more similar. CYP3A7 has a specific role in hydroxylation of retinoic acid and
      16alpha-hydroxylation of steroids, and is therefore of relevance both to normal
      development and carcinogenesis.CYP3A43 is the most recently discovered CYP3A
      isoform. In addition to a low level of expression in liver, it is expressed in
      prostate and testis. Its substrate specificity is currently unclear.
      Polymorphisms predicting absence of active enzyme have been identified.

PMID- 16430310
TI  - Mass balance studies, with a focus on anticancer drugs.
AB  - The importance of in-depth knowledge about the pharmacokinetics of a drug is
      evident because pharmacokinetic behaviour may correlate with activity and
      toxicity. The most elaborate pharmacokinetic investigation is a so-called mass
      balance study employing a radioactive tracer. A mass balance study investigates
      the plasma pharmacokinetics and excretion of both the unchanged drug and the
      total radioactivity (drug and metabolites), and allows elucidation of the
      metabolic fate of a drug. The main objective is the maximum recovery of the
      radioactive dose in urine and faeces. However, there is little concrete guidance
      on how to perform or assess such a mass balance study. Based on a critical review
      of the available literature and regulation, we discuss the design, conduct and
      evaluation of mass balance studies. The study must be preceded by pre-clinical
      studies to optimise the design. Compliance with available regulation (US FDA is
      more specific than European guidelines), choice of radioisotope (tritium may be
      lost and is consequently used less often), selection of subjects and safe
      administration of a relevant dose are critical. The drug (both the labelled and
      the non-labelled portion of the dose) must be prepared, characterised and
      administered, and the biological samples must be collected and analysed properly
      to obtain reliable and meaningful results. A recent development is the use of
      highly sensitive accelerator mass spectrometry for (14)C-detection, which allows
      the use of much lower amounts of radioactivity. Calculating the mass balance
      requires quantification of any possible losses of radioactivity during the study,
      e.g. during administration (adsorption to tubing). Total recovery should be at
      least 90% of the administered dose. A lower recovery, which is not uncommon, must
      be explained by biological factors such as a long decay half-life, irreversible
      binding to tissue components, or loss through expiration. The extent and
      relevance of metabolism is determined by comparing the pharmacokinetics of the
      unchanged drug and the total radioactivity. Metabolic profiling supplements
      existing knowledge of metabolism. We illustrate the important aspects of a mass
      balance study with literature on anticancer drugs. This review could serve as
      guidance for future mass balance studies.

PMID- 16430311
TI  - Population pharmacokinetics of tacrolimus in whole blood and plasma in asian
      liver transplant patients.
AB  - OBJECTIVES: The objectives of this study were to develop population
      pharmacokinetic models of tacrolimus in an Asian population with whole blood and
      plasma drug concentration data, to compare the variability of the pharmacokinetic
      parameters in these two matrices and to search for the main patient
      characteristics that explain the variability in pharmacokinetic parameters. STUDY
      DESIGN: Prospective pharmacokinetic assessment followed by model fitting.
      PATIENTS: Whole blood samples from 31 liver transplant patients in a local
      hospital receiving oral tacrolimus as part of their immunosuppressive therapy
      were assessed. Plasma samples from 29 of the 31 patients were also evaluated.
      Concentrations of tacrolimus in whole blood and plasma were determined by an
      electrospray high-performance liquid chromatography with tandem mass
      spectrometry. Two hundred and thirteen whole blood and 157 plasma tacrolimus
      concentrations were used for building two nonlinear mixed-effects population
      models to describe the disposition of tacrolimus in whole blood and plasma,
      respectively. Covariates that were investigated included demographic
      characteristics, biological markers of liver and renal functions, corticosteroid
      dose and haematological parameter. RESULTS: A one-compartment model was used to
      describe the whole blood and plasma concentration-time data of tacrolimus after
      oral administration. For the whole blood population model, the population
      estimates of the first-order absorption rate constant (k(a)), apparent clearance
      based on whole blood concentration after oral administration (CL(B)/F) and
      apparent volume of distribution based on whole blood concentrations after oral
      administration (V(d,B)/F) were 2.08h(-1), 14.1 L/h and 217L, respectively. The
      coefficient of variations (CVs) of interpatient variabilities in CL(B)/F and
      V(d,B)/F were 65.7% and 63.8%, respectively. Bodyweight, liver and renal function
      influenced CL(B)/F, while height and haematocrit influenced V(d,B)/F. The
      residual (unexplained) variability was 34.8%. For the plasma population model,
      the population estimates of the k(a), apparent clearance based on plasma
      concentrations after oral administration (CL(P)/F) and apparent volume of
      distribution based on plasma concentrations after oral administration (V(d,P)/F)
      were 5.21h(-1), 537 L/h and 563L, respectively. The CVs of interpatient
      variabilities in CL(P)/F and V(d,P)/F were 96.0% and 105.4%, respectively.
      Bodyweight was found to influence CL(P)/F, while the erythrocyte-to-plasma
      concentration ratio influenced V(d,P)/F. The residual (unexplained) variability
      was 49.8% at the mean plasma concentration of 1.1 ng/mL. CONCLUSIONS: Whole blood
      and plasma population pharmacokinetic models of tacrolimus in Asian adult and
      paediatric liver transplant patients were developed using prospective data in a
      clinical setting. This has identified and quantified sources of interindividual
      variability in CL(B)/F, V(d,B)/F, CL(P)/F and V(d,P)/F of tacrolimus in Asian
      liver transplant patients. Information derived from the whole blood population
      model may subsequently be used by clinicians for dosage individualisation through
      Bayesian forecasting.

PMID- 16430312
TI  - Pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor
      ximelagatran in young healthy Japanese men.
AB  - BACKGROUND AND OBJECTIVE: The direct thrombin inhibitor ximelagatran, which is
      rapidly bioconverted to its active form melagatran after oral administration, is
      being developed for the prevention and treatment of thromboembolism. This study
      assessed the effects of food and repeated dosing on the pharmacokinetics and
      pharmacodynamics of melagatran after oral administration of ximelagatran to young
      healthy Japanese males. METHODS: In part one of the two-part study, volunteers (n
      = 24) were randomised to receive in a crossover fashion a single oral dose of
      ximelagatran 48mg with or without breakfast on 2 days separated by a 2- to 7-day
      washout period. In the second part of the study, all volunteers received oral
      doses of ximelagatran 48mg every 12 hours for 5 days followed by a single dose on
      the morning of day 6. RESULTS: The area under the plasma concentration-time curve
      (AUC), peak plasma concentration (C(max)) and urinary excretion of melagatran did
      not differ as a function of whether ximelagatran was taken with or without food.
      The relationship between the melagatran plasma concentration and activated
      partial thromboplastin time (aPTT, which reflects the thrombin inhibitory effect
      of melagatran) was also independent of concomitant food intake. During repeated
      dosing, steady-state plasma concentrations of melagatran were achieved after the
      second dose of ximelagatran on day 1 and remained stable through the rest of the
      dosing period. The melagatran AUC and C(max) increased slightly (by 18% and 22%,
      respectively) on day 6 compared with day 1. The interindividual variability in
      the melagatran AUC and C(max) remained low, as reflected by coefficients of
      variation of <20% on both day 1 and day 6. The amount of melagatran excreted in
      urine remained stable over the 6 days of repeated dosing. CONCLUSION: The
      pharmacokinetics, pharmacodynamics, safety and tolerability of melagatran after
      oral administration of ximelagatran were not affected by food or repeated dosing
      in healthy Japanese volunteers.

PMID- 16430313
TI  - Comparable pharmacokinetics and pharmacodynamics of melagatran in Japanese and
      caucasian volunteers after oral administration of the direct thrombin inhibitor
      ximelagatran.
AB  - OBJECTIVES: Two studies were conducted to elucidate the pharmacokinetics and
      pharmacodynamics of melagatran after administration of the oral direct thrombin
      inhibitor ximelagatran to Caucasian and Japanese volunteers. METHODS: In study 1,
      with a single-blind, parallel-group design, young Japanese and Caucasian male
      volunteers were randomised to receive four single escalating oral doses of
      ximelagatran (12, 24, 36 and 60mg on separate days; n = 27 per ethnic group) or
      placebo (n = 6 per ethnic group). In study 2, with an open-label design, elderly
      Japanese male volunteers (n = 12) received three single escalating oral doses of
      ximelagatran (12, 24 and 36mg on separate days). RESULTS: Regardless of the
      ethnicity or age of the volunteers, ximelagatran given in single oral doses was
      rapidly absorbed and bioconverted to melagatran, and the melagatran area under
      the plasma concentration-time curve (AUC) and peak plasma concentration (C(max))
      increased in proportion with the ximelagatran dose, with only small deviations
      from absolute linearity. Higher melagatran AUC and C(max) were observed in young
      Japanese volunteers compared with young Caucasian volunteers, and in elderly
      Japanese volunteers compared with young Japanese volunteers. These results appear
      to be attributed to weight- and age-related decreases in renal elimination of
      melagatran rather than to absorption of ximelagatran and formation of melagatran.
      The pattern of metabolites in plasma and urine was comparable between young
      Japanese and Caucasian volunteers, and between young and elderly Japanese
      volunteers. The melagatran plasma concentration-activated partial thromboplastin
      time (aPTT, an ex vivo coagulation time measurement used to demonstrate
      inhibition of thrombin) relationship did not differ significantly between young
      Japanese and Caucasian volunteers or between young and elderly Japanese
      volunteers. CONCLUSIONS: Ethnicity does not affect the absorption of ximelagatran
      or the formation of melagatran or the melagatran plasma concentration-aPTT
      relationship. The elimination of melagatran is correlated with renal function.

PMID- 16430315
TI  - 'Hedged' prescribing for partially compliant patients.

PMID- 16430314
TI  - Compliance-guided therapy : a new insight into the potential role of clinical
      pharmacologists.
AB  - BACKGROUND AND OBJECTIVE: In the field of drug noncompliance, we investigated an
      original approach that could give the prescribing physician, in collaboration
      with a clinical pharmacologist, an active role. The aim here is for the
      prescribing physician to take compliance into account so as to provide an
      optimised prescription (choice of molecule prescribed and its rhythm of
      administration) adapted to each patient. The example considered is that of oral
      anticoagulant treatment prescribed long-term. METHODS: In order to investigate
      the choice of the best molecule and treatment regimen for a given noncompliance
      pattern, we performed an in silico study with two oral anticoagulant agents,
      warfarin and acenocoumarol, each taken in one or two daily doses. Three linked
      models were used: the first model generated specific noncompliance patterns, the
      second model described the pharmacokinetics of oral anticoagulant agents and the
      third model summarised the pharmacokinetic-pharmacodynamic relations. RESULTS:
      Considering different patterns of noncompliance (including timing errors in drug
      intake and the phenomenon of drug holidays) and comparing warfarin with
      acenocoumarol, we identified different situations in which one agent (prescribed
      once or twice daily) could clearly minimise both the thromboembolic and
      haemorrhagic risks. However, for some specific noncompliance patterns, the choice
      of the optimal therapy should also be guided by the basal individual
      thromboembolic and haemorrhagic risks. CONCLUSION: Individualisation of drug
      therapy involves both drug dose and drug choice. In addition to the classical
      approach (i.e. drug level measurements, enzyme assays and even genetic sequence
      data), our study suggests that compliance-guided therapy may represent a
      potential, evolving way for the individualisation of prescriptions.

PMID- 16430316
TI  - Altering TV viewing habits: an unexplored strategy for adult obesity
      intervention?
AB  - OBJECTIVES: To review literature evaluating whether television (TV) viewing
      reduction is a promising behavioral target for obesity treatment programs for
      adults. METHODS: Studies examining associations between TV viewing and obesity in
      adults were reviewed, as well as relevant pediatric literature. Interventions to
      reduce TV viewing among children were examined to inform adult interventions.
      RESULTS: Adult TV viewing has been consistently associated with greater obesity
      risk in cross-sectional and longitudinal studies. Strategies to alter TV viewing
      have been demonstrated effective among children but have not been tested in
      adults. CONCLUSIONS: Evaluation of the efficacy of targeting TV viewing among
      adults on weight outcomes is warranted.

PMID- 16430317
TI  - Development of a social will for tobacco control index.
AB  - OBJECTIVE: To design a valid and reliable questionnaire to assess community
      support for controlling tobacco. METHODS: Four samples were obtained to test the
      psychometric properties of the Social Will for Tobacco Control Instrument.
      RESULTS: Principal components analysis found 2 factors accounted for 42.8%
      (personal support) and 9.7% (agency support) of the variance, respectively.
      Sensitivity was 93.7%, specificity was 90.6%, and validity was 92.3%. The
      instrument predicted, within 1%, the actual vote regarding a local clean indoor
      air ordinance. Stability reliability was .84 and .77 respectively for the 2
      factors. CONCLUSION: The SWTCI can help policy makers predict whether communities
      are supportive of clean indoor air ordinances.

PMID- 16430318
TI  - Participation in employer-sponsored wellness programs before and after
      retirement.
AB  - OBJECTIVES: To evaluate wellness program participation before and after
      retirement. METHODS: This retrospective cohort design compares 3 groups of
      employees: 1998-1999 retirees (N=6065), 1994-1995 retirees (N=5862), and 21,176
      employees who were still active as of 2002. Participation was compared over 2
      time periods for high-intensity and low-intensity programs. RESULTS:
      Significantly different participation rates were found among the 3 groups
      specific to program intensity. Participation before retirement is associated with
      higher participation after retirement regardless of program intensity (OR=3.8 for
      overall participation). CONCLUSIONS: Wellness programs can attract retirees,
      especially if they participated before retirement and are offered a variety of
      programs.

PMID- 16430320
TI  - Timely follow-up among multicultural women with abnormal mammograms.
AB  - OBJECTIVE: To examine factors influencing time from screening to final diagnosis
      among multicultural women with abnormal mammograms using the precede-proceed
      model. METHODS: Staff of 58 clinics and a sample of 436 women served by these
      clinics were interviewed and their medical records examined. RESULTS: Longer
      duration from screening to diagnosis was associated with speaking Spanish and
      having clinic staff make appointments. Ease of access to health care, provision
      of early morning screening services and higher levels of patient anxiety
      shortened the time to diagnosis. CONCLUSION: The precede-proceed model is useful
      in delineating personal and structural factors that affect timely diagnosis.

PMID- 16430319
TI  - Ethnic differences in elders' home remedy use: sociostructural explanations.
AB  - OBJECTIVE: To determine if ethnic differences in elders' use of home remedies are
      explained by structured inequalities. METHOD: Dichotomous indicators of "food"
      and "other" home remedies were obtained from a randomly selected cohort of older
      adults with diabetes (N=701). Analyses evaluated if differences in availability
      of care, economic hardship, and health status explained ethnic differences in
      home remedy use. RESULTS: Differences in residential location, discretionary
      money, and health partially explained greater home remedy use among Black and
      Native American elders relative to whites. CONCLUSIONS: Ethnic differences in
      elders' use of home remedies are not largely attributed to socially structured
      inequalities.

PMID- 16430321
TI  - Media and secondhand smoke exposure: results from a national survey.
AB  - OBJECTIVES: To investigate whether associations between anti-secondhand smoke
      (SHS) media, social cognitions about SHS, and home restrictions on smoking follow
      patterns observed in smoking behavior. METHODS: Based on a nationally
      representative sample of 2348 US adults drawn from the American Legacy
      Foundation's American Smoking and Health Survey, we tested relationships among
      scales of anti-SHS media, social cognitions, and home restrictions. RESULTS: We
      found anti-SHS media and SHS cognitions, as well as social cognitions and home
      restrictions, to be significantly associated. Social cognitions mediated the
      relationship between anti-SHS media and home restrictions. CONCLUSIONS:
      Previously observed relationships between media, social cognitions, and smoking
      also exist for SHS. Anti-SHS media campaigns to increase home restrictions may
      help to reduce SHS exposure.

PMID- 16430322
TI  - Childbearing among daughters of parents with HIV.
AB  - OBJECTIVE: To examine first childbearing and its predictors among daughters of
      parents with HIV. METHOD: Pairs of parents with HIV and their adolescent
      daughters (n = 181) participated in a randomized, controlled-intervention trial
      designed to improve coping skills within the family, and were monitored up to 7
      years. RESULTS: Overall, daughters of HIV parents had a high rate of early
      childbearing compared to national and local rates. First childbearing tended to
      be delayed by (a) being in a coping intervention, (b) being less emotionally
      distressed, (c) receiving academic counseling, and (d) having a positive
      perception of their family's finances. CONCLUSIONS: HIV has a negative
      intergenerational impact, particularly on depressed young people, which may be
      buffered by interventions enhancing coping and academic counseling.

PMID- 16430323
TI  - Does religion influence patient satisfaction?
AB  - OBJECTIVES: To determine if patient satisfaction varies by level of individual
      religiosity. METHODS: Data from the Health and Retirement Study (HRS), a
      nationally representative sample of older adults in the United States, were used
      to assess the relationship between religious salience (importance) and patients'
      satisfaction with their health care encounters. RESULTS: Higher levels of
      religious salience are significantly related to being very satisfied with one's
      health care, even after demographic, social, and health variables are taken into
      account. CONCLUSIONS: Researchers, practitioners, and administrators should be
      aware that religion may significantly influence how patients rate their health
      care experiences.

PMID- 16430324
TI  - Reasons for contraceptive nonuse at first sex and unintended pregnancy.
AB  - OBJECTIVE: To examine reasons for contraceptive nonuse at first sex and
      subsequent unintended pregnancy among women attending family planning and
      prenatal clinics. METHODS: Data come from the Determinants of Unintended
      Pregnancy Risk in New Orleans study. Reasons for nonuse by age, partner's age,
      and pregnancy status are compared. RESULTS: Concern about parents' finding out
      about sexual activity was a common reason for nonuse at first sex and first
      unintended pregnancy. Problems accessing and discontinuation of contraception
      were reasons given at second or higher-order unintended pregnancy. CONCLUSIONS:
      Reasons for nonuse vary by event and age at event. Providers should consider
      various reasons when counseling patients on contraceptive options.

PMID- 16430325
TI  - Predictors of smokeless tobacco initiation in a young adult military cohort.
AB  - OBJECTIVE: To identify predictors of smokeless tobacco (ST) initiation among
      young adults. METHODS: A military cohort (N=28,229) was analyzed to identify
      variables associated with ST initiation. RESULTS: Baseline current cigarette
      smoking at baseline was a strong predictor for any ST use (OR 3.88; 95% CI: 3.33
      4.52) and daily ST use (OR 3.01, 2.34-3.88) as was experimental ST use for any
      (OR 2.39, 2.09-2.73) and daily ST use (OR 2.41, 1.93-3.01). CONCLUSIONS: Smoking
      and previous ST use are strong predictors for ST use in adults. Research is
      needed to characterize ST initiation and changes in smoking behavior over time.

PMID- 16430326
TI  - A nonconformist account of the Asch experiments: values, pragmatics, and moral
      dilemmas.
AB  - This article offers a new approach to Asch's (1956) influential studies relating
      physical and social perception. Drawing on research on values, conversational
      pragmatics, cross-cultural comparisons, and negotiation, the authors challenge
      the normative assumptions that have led psychologists to interpret the studies in
      terms of conformity. A values-pragmatics account is offered that suggests that
      participants attempt to realize multiple values (e.g., truth, social solidarity)
      in an inherently frustrating situation by tacitly varying patterns of dissent and
      agreement to communicate larger scale truths and cooperative intentions.
      Alternative theories (e.g., embarrassment, attribution) are compared and
      empirical implications of the values-pragmatics account are evaluated. The
      possibility of multiple strategies promoting group survival and the proper role
      of moral evaluation in social psychological research are considered.

PMID- 16430327
TI  - Solving the emotion paradox: categorization and the experience of emotion.
AB  - In this article, I introduce an emotion paradox: People believe that they know an
      emotion when they see it, and as a consequence assume that emotions are discrete
      events that can be recognized with some degree of accuracy, but scientists have
      yet to produce a set of clear and consistent criteria for indicating when an
      emotion is present and when it is not. I propose one solution to this paradox:
      People experience an emotion when they conceptualize an instance of affective
      feeling. In this view, the experience of emotion is an act of categorization,
      guided by embodied knowledge about emotion. The result is a model of emotion
      experience that has much in common with the social psychological literature on
      person perception and with literature on embodied conceptual knowledge as it has
      recently been applied to social psychology.

PMID- 16430328
TI  - The paranoid optimist: an integrative evolutionary model of cognitive biases.
AB  - Human cognition is often biased, from judgments of the time of impact of
      approaching objects all the way through to estimations of social outcomes in the
      future. We propose these effects and a host of others may all be understood from
      an evolutionary psychological perspective. In this article, we elaborate error
      management theory (EMT; Haselton & Buss, 2000). EMT predicts that if judgments
      are made under uncertainty, and the costs of false positive and false negative
      errors have been asymmetric over evolutionary history, selection should have
      favored a bias toward making the least costly error. This perspective integrates
      a diverse array of effects under a single explanatory umbrella, and it yields new
      content-specific predictions.

PMID- 16430332
TI  - Lessons learned.

PMID- 16430329
TI  - How interpersonal motives clarify the meaning of interpersonal behavior: a
      revised circumplex model.
AB  - Circumplex models have organized interpersonal behavior along 2 orthogonal
      dimensions--communion (which emphasizes connection between people) and agency
      (which emphasizes one person's influence over the other). However, many empirical
      studies have disconfirmed certain predictions from these models. We therefore
      revised the model in 4 ways that highlight interpersonal motives. In our
      revision: (a) the negative pole of communion is indifference, not hostility; (b)
      a given behavior invites (not evokes) a desired reaction from the partner; (c)
      the complement of a behavior is a reaction that would satisfy the motive behind
      that behavior; (d) noncomplementary reactions induce negative affect. If the
      motive is unclear, the meaning of the behavior is ambiguous. This ambiguity helps
      explain failures in social support, miscommunications in everyday life, and
      features of most personality disorders. The model emphasizes measurable
      individual differences: Reactions that are complementary for one person need not
      be complementary for another.

PMID- 16430331
TI  - Who makes the rules?

PMID- 16430333
TI  - Lack of pain assessment for patients with cancer presenting to the emergency
      department with pain complaints: can we improve with a simple intervention?

PMID- 16430334
TI  - Palatable message? Change the language!

PMID- 16430335
TI  - Half-full or half-empty: a response.

PMID- 16430336
TI  - Half-full, half-empty.

PMID- 16430339
TI  - Palliative care/intensive care unit interface: opportunities for mutual
      education.

PMID- 16430340
TI  - Formal ABMS and ACGME recognition of hospice and palliative medicine expected in
      2006.

PMID- 16430341
TI  - PC-FACS: a real-time evidence resource for busy palliative care clinicians.

PMID- 16430342
TI  - Duloxetine versus routine care in the long-term management of diabetic peripheral
      neuropathic pain.
AB  - INTRODUCTION: Duloxetine hydrochloride is a dual reuptake inhibitor of both
      serotonin and norepinephrine. In the present open-label study, the safety of
      duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks was
      evaluated and compared to routine care in the therapy of patients diagnosed with
      diabetic peripheral neuropathic pain (DPNP). METHODS: Patients who completed a 13
      week, double-blind, duloxetine and placebo acute therapy period were rerandomly
      assigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N=161) or routine
      care (N=76) for an additional 52 weeks. Routine care consisted primarily of
      gabapentin, amitriptyline, and venlafaxine. The study included male or female
      outpatients 18 years of age or older with a diagnosis of DPNP caused by type 1 or
      type 2 diabetes. RESULTS: A higher percentage of routine care-treated patients
      experienced 1 or more serious adverse events. No statistically significant
      therapy-group difference was observed in the overall incidence of treatment
      emergent adverse events (TEAEs). The TEAEs reported by 10% or more of duloxetine
      60 mg BID-treated patients were nausea, and by the routine care-treated patients
      were peripheral edema, pain in the extremity, somnolence, and dizziness.
      Duloxetine did not appear to adversely affect glycemic control, lipid profiles,
      nerve function, or the course of DPNP. There were no statistically significant
      therapy-group differences observed in the 36-item Short-Form Health Survey
      subscales or in the EuroQol 5-Dimension Questionnaire. CONCLUSIONS: In this
      study, duloxetine was safe and well tolerated compared to routine care in the
      long-term management of patients with DPNP.

PMID- 16430343
TI  - Factors associated with reductions in patients' analgesia at hospital discharge.
AB  - OBJECTIVE: To describe the patterns of opioid prescribing and the factors
      associated with reductions in the potency of patients' analgesic medications at
      the time of hospital discharge. DESIGN: Prospective cohort. SETTING: Two hundred
      forty-four patients (171 surgical and 73 nonsurgical) hospitalized in an urban
      academic medical center who have experienced moderate or severe pain and who are
      taking opioid analgesics prior to discharge. OUTCOME: Step-down (or reduction) in
      the potency of patients' analgesic medication at the time of discharge. A step
      down is defined as the analgesic medication that a patient is prescribed for
      outpatient analgesia at the time of discharge being less potent then the last
      pain medication administered to that patient just prior to hospital discharge.
      RESULTS: Thirty-three percent of all patients had reductions in the potency of
      their opioid pain medication at the time of discharge (36% for surgical and 26%
      for nonsurgical patients). For nonsurgical patients, we found a trend toward
      Hispanic ethnicity being an independent risk factor for having a step-down in
      analgesic potency at discharge (odds ratio [OR]: 3.7, 95% confidence interval
      [CI]: 0.9-14.9). CONCLUSION: Physicians frequently reduce the potency of
      hospitalized patients' pain medications at discharge and Hispanic patients may be
      at increased risk of this occurring. Further research is needed to determine if
      the reductions in analgesic potency we observed are associated with poor
      posthospital pain outcomes.

PMID- 16430344
TI  - Successful and unsuccessful outcomes with long-term opioid therapy: a survey of
      physicians' opinions.
AB  - BACKGROUND: The attitudes, beliefs, and experience of physicians will influence
      how they view the use of opioids for chronic nonterminal pain. OBJECTIVE: To
      survey pain specialists and primary care providers (PCPs) to obtain their opinion
      and attitude on aberrant drug-taking behaviors. DESIGN: We surveyed three
      physician groups, mailing 250 surveys followed by two followups. The survey
      consisted of (1) questions about beliefs in the effectiveness of long-term opioid
      therapy and successful and unsuccessful outcomes and (2) a ratings section for
      possible indicators of unsuccessful long-term opioid treatment. RESULTS: In total
      147 questionnaires (82 PCPs, 65 pain specialists) were returned. Pain specialists
      reported a greater number of patients undergoing long-term opioid therapy
      compared to nonpain specialists. Opinion regarding the effectiveness of long-term
      opioid therapy among all physicians was mixed but there was no significant
      difference between pain specialists and PCPs. There was agreement among
      physicians with regard to highly aberrant behaviors being indicators of failed
      long-term opioid therapy. The ratings of the following indicators showed
      differences between each group: no improvement in pain control, not being able to
      return to work, and a deterioration in relationships with others. Physicians
      reported increases or decreases in function to be the most important successful
      or unsuccessful outcome, respectively. CONCLUSIONS: This preliminary survey
      showed consensus among physicians that highly aberrant behaviors indicate a
      failure of chronic opioid therapy. However, when considering less egregious
      behaviors, it would appear a physician's experience and the number of patients
      they had taking opioids influenced their opinion.

PMID- 16430345
TI  - Olfactory function in oncologic hospice patients.
AB  - INTRODUCTION: Normal sense of smell is important for well being. Although cancer
      is reported to be associated with impaired olfactory function, very few studies
      have directly evaluated this effect. PATIENTS AND METHODS: We performed a
      quantitative analysis of olfactory status in 42 hospice patients in a hospital
      based hospice facility. Olfaction was assessed using the "Sniffin' Sticks"
      (Burghart Medical Technology, Tinsdaler, Germany) kit. RESULTS: Twenty-five
      patients (60%) were found to be hyposmic. CONCLUSION: Study results indicate the
      high incidence of decreased olfactory function among hospice patients.

PMID- 16430346
TI  - Changes in prognostic awareness among seriously ill older persons and their
      caregivers.
AB  - PURPOSE: To examine changes in patients' and caregivers' understanding of
      prognosis with progression of the patient's illness. SUBJECTS AND METHODS:
      Community-dwelling persons 60 years of age and older who were seriously ill with
      cancer, congestive heart failure, or chronic obstructive pulmonary disease and
      their caregivers were interviewed every 4 months and more frequently with a
      decline in the patient's status for up to one year. We examined responses to, "If
      you had to take a guess, how long do you think that (you/the patient) might have
      to live?" at baseline and at the interview closest to death. RESULTS: Among 218
      patients, 87 died within 1 year. At their initial interview 46% were uncertain
      about their life expectancy (LE) and 9% believed LE was 1 year or less; at their
      final interview, 55% were uncertain and 17% believed LE was 1 year or less. At
      the caregiver's initial interview, 29% were uncertain about the patient's LE and
      20% believed LE was 1 or less; at their final interview, 30% were uncertain and
      34% believed LE was 1 year or less. Among those interviewed within 30 days of the
      patient's death, 31% of patients and 52% of caregivers believed LE was 1 year or
      less. Patients' estimates of the LE did not differ according to their diagnosis.
      CONCLUSIONS: There was little change in prognostic awareness over time. Even
      close to death, a large proportion of patients and caregivers were uncertain
      about prognosis, and few believed the patient had a limited life expectancy.
      Whether or not patients should know their prognosis is the subject of active
      debate; the persistence of prognostic misperception suggests that prognostic
      awareness may be difficult to change.

PMID- 16430347
TI  - Personal and professional experiences of pediatric residents concerning death.
AB  - BACKGROUND: The American Academy of Pediatrics (AAP) statement on Pediatric
      Palliative Care has emphasized the importance of identifying barriers and
      facilitators to effective palliative care. OBJECTIVES: To survey pediatric
      residents about their personal and professional experiences concerning death and
      determine factors associated with guilt (a potential barrier) and attendance at
      patient funerals (a potential facilitator). DESIGN/METHODS: PL-2 residents were
      surveyed midway through pediatric residency. Both personal and professional
      attitudes and experiences about death were solicited. RESULTS: Seventy-nine (90%)
      PL-2 residents completed the survey from 1997-2000. While 91% reported that a
      close family member or friend had died, 75% recalled that their family had not
      openly discussed issues of death. Thus far in their career, residents reported
      encountering a mean of 9.4 patients who had died (+/-6.4; range, 0-30 deaths) and
      39% expressed guilt about a death. Those who felt guilt about a death were more
      likely to state they felt responsible (p<0.01) but less likely to think about
      their own death (p<0.01). While 23% had attended a patient's funeral, 42%
      expressed fear of attending. The mean number of times a resident informed a
      family of a patient's death was slightly higher in those who attended a patient's
      funeral, and approached statistical significance. CONCLUSIONS: By midresidency,
      these pediatric residents have had many personal and professional experiences
      with death. Residency training programs must provide venues for residents to
      address bereavement, facilitate the integration of these experiences, and provide
      time to attend funerals.

PMID- 16430348
TI  - End-of-life care: a retreat format for residents.
AB  - BACKGROUND: The challenge of teaching end-of-life care involves finding ways to
      incorporate both the science and the art of medicine. OBJECTIVES: To develop a
      curriculum so that internal medicine residents could more effectively (1) elicit
      patient's values, goals, and preferences for health care at the end of life, (2)
      communicate "bad news," (3) discuss patient preferences for nutrition and
      hydration, ventilator withdrawal, and cardiopulmonary resuscitation, (4)
      prescribe opioids using different routes of administration and, (5) recommend
      appropriate treatment of symptoms common at the end of life. DESIGN: The daylong
      retreat utilized case presentations and problems for presenting scientific
      content and the film Wit to convey information related to communication, whole
      patient assessment, and the palliative care approach. Materials from the
      Education for Physicians on End-of-Life Care (EPEC) project and the film Wit
      provided the main educational resources. SETTING: All second-year internal
      medicine, and family medicine residents, and geriatric fellows from a community
      hospital in South Carolina attended. RESULTS: The residents positively evaluated
      the seminar content and format. Pretests and posttests revealed that residents
      significantly improved their knowledge regarding pain management (p<0.001),
      symptom management (p<0.001) and whole-patient assessment (p<0.014). Scores on
      the pretest and posttest related to communication skills did not significantly
      change (p=0.092). Yet, qualitative postretreat evaluations showed that residents
      perceived that the retreat would affect their communication with patients and
      other less easily quantifiable factors. CONCLUSION: Quantitative methods that
      work well for documenting scientific principles and learning may not apply as
      well in assessing the art of medicine.

PMID- 16430349
TI  - Impact of a volunteer companion program on nursing students' knowledge and
      concerns related to palliative care.
AB  - BACKGROUND: Deficiencies in end-of-life education may explain nursing students'
      reports of feeling anxious and unqualified to care for dying patients. A
      volunteer Palliative Care Companion program was developed to provide
      undergraduate nursing students with an experiential learning opportunity by
      spending time with dying patients and their families. OBJECTIVE: To evaluate the
      impact of the Palliative Care Companion program on nursing students' knowledge,
      attitudes, and concerns about providing palliative care, and to describe
      companion students' volunteer activities. DESIGN: Quasiexperimental controlled
      pretest-posttest design. SETTING/SUBJECTS: Fifty-two undergraduate nursing
      students (32 companion students, 20 controls) at a midwestern U.S. university
      with an affiliated hospital-based palliative care service. MEASUREMENTS: All
      participants completed the Palliative Care Quiz for Nurses, Attitudes Toward
      Palliative Care, and Concern About Caring for Dying Patients questionnaires at
      the beginning and end of the semester. Companion subjects also kept a journal
      describing their palliative care experiences. RESULTS: Attitude scores were not
      analyzed because of poor internal consistency of the questionnaire. Changes in
      scores on knowledge items did not reach significance. Concern scores decreased
      significantly from pretest to posttest in the companion group. After adjusting
      for pretest concern score, there was a trend toward lower concern score in the
      companion group compared to controls (p=0.07). Companion students' journals
      described activities including visiting patients, viewing end-of-life videos,
      attending educational and public lectures, independent reading, and making
      bereavement phone calls to family members. CONCLUSIONS: The Palliative Care
      Companion program did not produce significant improvements in knowledge and
      concerns compared to controls, but companion students described their
      participation as a meaningful learning experience.

PMID- 16430350
TI  - Is there no place like home? Caregivers recall reasons for and experience upon
      transfer from home hospice to inpatient facilities.
AB  - OBJECTIVE: To describe caregivers' reasons for transfer from home hospice to
      inpatient facilities, preferences for site of care and death, and their
      experiences during these transfers. DESIGN: Retrospective qualitative analysis of
      interviews with caregivers of deceased hospice patients who had undergone
      transfer. SETTING: A university-affiliated community hospice provider. SUBJECTS:
      Caregivers of deceased hospice patients who transferred to an acute care
      hospital, a freestanding inpatient hospice facility, or a nursing home while
      enrolled in hospice and died between January 2003 and February 2004.
      MEASUREMENTS: A semistructured interview protocol was developed and used for all
      interviews. Interviews were coded for reasons for transfer, preferences for site
      of care and death, and experience upon transfer using a grounded theory approach.
      RESULTS: Patients transferred because of an acute medical event, an uncontrolled
      symptom, imminent death, or inability to provide needed care safely at home.
      Although all caregivers expressed a strong preference for care at home, other
      concerns such as pain and symptom control, safety, and quality and quantity of
      life became more important with time. We found significant variation in specific
      preferences regarding care and site of death. Satisfaction with care at the
      transfer facilities was determined by clarifying goals of care, following
      treatment preferences, providing personalized care, and the patient's
      environment. CONCLUSIONS: Hospice patients usually transfer to facilities to
      accomplish goals consistent with good end-of-life care. We can improve their
      experience by treating patients and their caregivers as unique individuals,
      exploring and respecting treatment preferences, and creating a pleasant physical
      environment.

PMID- 16430351
TI  - Outcome evaluation of a randomized trial of the PhoenixCare intervention: program
      of case management and coordinated care for the seriously chronically ill.
AB  - OBJECTIVE: To document outcomes of a randomized trial of the PhoenixCare
      demonstration program of palliative care and coordinated care/case management for
      seriously chronically ill individuals who simultaneously received active
      treatment from managed care organizations (MCOs). DESIGN: Patients, continuously
      enrolled between July 1999, and March 2001, were randomly assigned to the
      PhoenixCare program or a control group receiving usual MCO care. SETTING: Hospice
      of the Valley, Phoenix, Arizona. PARTICIPANTS: Participants were 192 patients
      with chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF),
      who had an estimated 2-year life expectancy. INTERVENTION: Intensive home-based
      case management provided by registered nurse casemanagers, in coordination with
      patients' existing source of medical care, comprised the intervention. Program
      foci included disease and symptom management, patient self-management of illness
      and knowledge of illness-related resources, preparation for end-of life, physical
      and mental functioning, and utilization of medical services. OUTCOME MEASURES:
      Outcomes, assessed every 3 months by telephone interview, included measures
      related to all program foci; the SF-36 was used to evaluate physical and mental
      functioning; emergency department visits exemplified medical service utilization.
      RESULTS: Compared to controls, PhoenixCare patients exhibited significantly
      better outcomes on self-management of illness, awareness of illness-related
      resources, and legal preparation for end of life. They reported lower symptom
      distress, greater vitality, better physical functioning and higher self-rated
      health than randomized controls. Emergency department utilization was equivalent
      across groups. Patients with COPD showed stronger responsiveness to the
      intervention. CONCLUSION: A novel model of patient care that combined greatly
      enhanced palliative carefocused case management with ongoing MCO-based treatment
      was associated with improved functioning of chronically severely ill patients in
      the last years of life.

PMID- 16430352
TI  - Elder abuse at end of life.
AB  - CONTEXT: Advances in health care and changing demographics have led to an aging
      population whose care at the end of life has become complex. Patients at the end
      of life, by the nature of their clinical and social circumstances, are at high
      risk for elder abuse. Underreporting of elder abuse is a growing concern. The
      clinical presentation of abuse may overlap with the natural dying process,
      further compounding the problem. EVIDENCE ACQUISITION: Articles were obtained
      through a PubMed search using the terms "elder abuse" and "elder mistreatment"
      and from the University of California, Irvine's Elder Abuse Forensic Center
      library. Additional references were followed through these first set of articles
      and also from colleagues expert in this field. EVIDENCE SYNTHESIS:
      Multidisciplinary teams have been shown to be the most effective intervention for
      the assessment and prevention of abuse. Most abuse occurs at home by family
      members; the hospice team may be the only outside professionals coming into the
      home. Caregiver stress and victim dependency increase the risk for abuse.
      Although physical abuse is the most commonly envisioned, neglect is the most
      common form of abuse. Financial abuse is often the underlying motivation for
      other forms of abuse. CONCLUSIONS: Health professionals have an ethical and legal
      responsibility to both report and work to prevent suspected abuse. The
      interdisciplinary team can make a significant impact on elder abuse, a major
      detriment on quality of life.

PMID- 16430353
TI  - Promoting excellence in end-of-life care: a report on innovative models of
      palliative care.
AB  - BACKGROUND: Promoting Excellence in End-of Life Care, a national program of The
      Robert Wood Johnson Foundation, funded 22 demonstration projects representing a
      wide range of health care settings and patient populations to develop innovative
      models for delivering palliative care that addressed documented deficiencies in
      the care of patients and families facing the final stage of life. OBJECTIVE: To
      determine the practicality (feasibility of development and operation as well as
      acceptance by stakeholders) of new models of care and to determine the impact of
      the models on access to, quality of and financing for palliative care. DESIGN:
      The program cannot report scientifically rigorous outcomes, but the grant-funded
      projects used a variety of methods and measures to assess acceptance of new
      models and their impact from the perspectives of various stakeholders, including
      patients and their families, clinicians, administrators and payers. While it is
      not possible to aggregate data across projects, the data reported to the
      Promoting Excellence national program office were used to describe program impact
      with respect to the practicality of palliative care service integration into
      existing clinical care settings (feasibility and acceptance by stakeholders), the
      availability and use of palliative care services (access), quality of care
      (conformance to patient expectations and accepted clinical standards) and costs
      of care. SETTINGS AND SUBJECTS: The 22 projects provided services in urban as
      well as rural settings, in integrated health systems, hospitals, outpatient
      clinics, cancer centers, nursing homes, renal dialysis clinics, inner city public
      health and safety net systems and prisons. Populations served included prison
      inmates, military veterans, renal dialysis patients, Native Americans, Native
      Alaskans, and African American patients, inner-city medically underserved
      patients, pediatric patients, and persons with serious mental illness patients.
      RESULTS: Hosting or adopting institutions sustained or expanded twenty of the 22
      models, and feedback from all stakeholders was positive. Project sites developed
      and utilized new palliative care services and addressed quality through
      implementation of new standards and clinical protocols. Costs of care, where they
      could be assessed, were unaffected or decreased for project patients versus
      historical or concurrent controls. CONCLUSIONS: The 22 Promoting Excellence in
      End-of Life Care projects demonstrated that by individualizing patient and family
      assessment, effectively employing existing resources and aligning services with
      specific patient and family needs, it is possible to expand access to palliative
      services and improve quality of care in ways that are financially feasible and
      acceptable to patients, families, clinicians, administrators, and payers.

PMID- 16430354
TI  - Comparison of medical treatments for the dying in a hospice and a geriatric
      hospital in Japan.
AB  - CONTEXT: Most older adults who die in Japan do so in the hospital without
      receiving hospice or palliative care. While there are some hospices in Japan,
      little is known about the care they provide to the elderly. OBJECTIVE: To clarify
      how the care of dying patients differs in a hospice and a geriatric hospital in
      Japan. DESIGN: Cohort study. SETTING: A hospice and a geriatric hospital in
      Japan. PARTICIPANTS: One hundred ninety-one inpatients aged 65 or older. MAIN
      OUTCOME: Areas of our interest: (1) gender and age; (2) primary disease(s) and
      cause of death; (3) observed symptoms/conditions and medical treatment or care
      conducted within 48 hours prior to death; (4) the actual topics leading to
      disclosure; and (5) whether or not advance directives had been given. RESULTS:
      The X2 test determined that there were statistically significant differences
      between a geriatric hospital and a hospice, with respect to mean age, diagnoses
      on admission, primary cause of death, symptoms/conditions, and the practice of
      medical interventions. However, controlling for patient characteristics and
      assuming a bivariate distribution between the probabilities of choosing a
      facility and of undergoing a medical procedure, we found that patients at the
      hospice were more likely to undergo treatment with opioids, urethral catheter,
      and oral medicine; such patients were less likely to undergo oxygen inhalation,
      total parenteral nutrition, and other intravenous drips. CONCLUSION: The hospice
      examined in this study was similar to the approach regarding medical treatments
      observed at the geriatric hospital.

PMID- 16430355
TI  - Editorial: supporting pediatric palliative care: helping ourselves.

PMID- 16430356
TI  - Palliative care for infants, children, adolescents, and their families.

PMID- 16430357
TI  - The helping relationship: beyond the best of intentions.

PMID- 16430358
TI  - Promoting advance directives among African Americans: a faith-based model.
AB  - BACKGROUND: Studies show that African Americans are less likely than other ethnic
      groups to complete advance directives. However, what influences African
      Americans' decisions to complete or not complete advance directives is unclear.
      METHODS: Using a faith-based promotion model, 102 African Americans aged 55 years
      or older were recruited from local churches and community-based agencies to
      participate in a pilot study to promote advance care planning. Focus groups were
      used to collect data on participants' preferences for care, desire to make
      personal choices, values and attitudes, beliefs about death and dying, and
      advance directives. A standardized interview was used in the focus groups, and
      the data were organized and analyzed using NUDIST 4 software (QRS Software,
      Victoria, Australia). RESULTS: Three fourths of the participants refused to
      complete advance directives. The following factors influenced the participants'
      decisions about end-of-life care and completion of an advance directive:
      spirituality; view of suffering, death, and dying; social support networks;
      barriers to utilization; and mistrust of the health care system. CONCLUSION: The
      dissemination of information apprises individuals of their right to self
      determine about their care, but educational efforts may not produce a significant
      change in behavior toward completion of advance care planning. Thus, ongoing
      efforts are needed to improve the trust that African Americans have in medical
      and health care providers.

PMID- 16430359
TI  - Caregivers and professionals partnership caregiver resource center: assessing a
      hospital support program for family caregivers.
AB  - BACKGROUND: Given that 71% of caregivers nationally report that they are caring
      for someone with a long-term or chronic illness, providing support to families
      from diagnosis to the bereavement phase--is essential. PURPOSE: This paper
      describes an exploratory assessment of a hospital-based support program for
      family caregivers, the Caregivers and Professionals Partnership (CAPP) Caregiver
      Resource Center. The goal of the program evaluation was to understand the
      challenges facing caregivers who used the Center, how social workers intervened
      and the results of their interventions. Authors suggest that caregivers benefit
      from social work interventions that focus both on the emotional impact of
      caregiving and the multiple resource issues caregivers face. METHODS: Social
      workers assisted more than half of participating caregivers with emotional coping
      issues as well as referrals to community resources. In approximately 75% of
      cases, social workers followed up with caregivers to engage them in services and
      ensure that they received ongoing support. FINDINGS: From the perspective of
      Resource Center social workers, their interventions enhanced caregivers'
      abilities to cope with their responsibilities. CONCLUSIONS: Supporting caregivers
      over time and following up to ensure that they access needed services are
      critical ways to help them cope with care of a loved one. Future research can
      focus on how to engage caregivers who are isolated or too overwhelmed to ask for
      help in order to increase their use of caregiver assistance programs.

PMID- 16430360
TI  - Nonoral hydration in palliative care #133.

PMID- 16430361
TI  - From generation to generation.

PMID- 16430362
TI  - Revealing images.

PMID- 16430363
TI  - Posttraumatic stress disorder at the end of life.

PMID- 16430367
TI  - Infections and the use of antibiotics in dying patients.

PMID- 16430369
TI  - Locomotor deficits and adaptive mechanisms after thoracic spinal cord contusion
      in the adult rat.
AB  - The rat is widely used for modeling human spinal cord injury (SCI) and
      paraplegia. However, quadruped animals adapt trunk, forelimb and hindlimb
      movements to compensate for deficits, improving their behavioral scores and
      complicating the interpretation of spontaneous and treatment-induced function
      recovery. The kinematics of locomotion was studied in rats, both normal and after
      SCI (T9 contusion), and variables indicative of hindlimb function were related to
      brain-spinal cord connections (BSCC) spared during lesioning. Normal animals
      showed forward velocities characteristic of fast walking. The hind paw was placed
      approximately three centimeters in front of the hip at the initial contact. Hip
      height decreased during the first third of hindlimb stance and increased later.
      Mild and moderate spinal cord contusions destroyed the gray matter and adjacent
      axons but spared the ventrolateral tracts to various degrees. Injured animals
      placed the hindpaw in a more caudal position than normal and showed reduced
      forward velocity and hip height. Knee extension was also impaired, and both
      hindlimb and forelimb steps were adapted to compensate for the deficits. BSCC was
      estimated by averaging the transverse area of white matter at the lesion
      epicenter and the percentage of brain neurons labeled after peroxidase injection
      into L2 and L3. Recovery of hindlimb motor function was proportional to the
      amount of BSCC. On average, injured animals retained 18% of BSSC and recovered
      23% of hindlimb function. These findings show that kinematic analysis is a
      reliable tool for assessing locomotor deficits and compensations and suggest
      limited spontaneous motor plasticity after SCI.

PMID- 16430370
TI  - Profound differences in spontaneous long-term functional recovery after defined
      spinal tract lesions in the rat.
AB  - The purpose of this study was to compare spontaneous functional recovery after
      different spinal motor tract lesions in the rat spinal cord using three methods
      of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal
      corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or the complete dorsal
      half of the spinal cord (Hx) at thoracic level T8. Functional recovery was
      monitored for 31 weeks. We found no recovery of consistent inter limb
      coordination in any experimental group over time using the BBB locomotor rating
      scale. Quantitative CatWalk analysis revealed significant differences between
      experimental groups for inter limb coordination (RI). RSTx and Hx animals showed
      a significant decrease in the RI, and only in the RSTx group did the RI improve
      from 6 weeks post-lesion onward. Significant differences between experimental
      groups in step sequence patterns and base of support were also observed. In the
      rope test all experimental groups had significantly higher error percentages
      compared to control animals. Tracing of the CST revealed enhanced collateral
      formation rostral to the lesion in the CSTx group, not in other groups. The
      results presented here show that locomotor function in all, but CSTx groups
      gradually improved over time. This is important for studies that employ
      pharmacological, cell-, and/or gene therapy- based interventions to improve
      axonal regeneration and functional recovery after spinal cord injury.

PMID- 16430371
TI  - Behavioral and histological characterization of unilateral cervical spinal cord
      contusion injury in rats.
AB  - Most experimental studies of spinal cord injury (SCI) in rats damage the thoracic
      cord, with the consequent functional loss being due to interruption of long
      tracts connecting the caudal spinal cord to the rostral nervous system. Less work
      has been done evaluating injury to the cervical cord, even though it is the most
      common level of human SCI. In addition to the long tracts, the cervical spinal
      cord contains the sensory and motor neurons responsible for upper extremity
      function. The purpose of this study was to further develop a rat model of
      cervical spinal cord contusion injury using a modified NYU/MASCIS weight drop
      device. Mild (6.25 mm) and moderate (12.5 mm) C5 unilateral injuries were
      produced. Behavioral recovery was examined using a grooming test, a paw
      preference test, a walkway test (The Catwalk), and a horizontal ladder test.
      Histological outcome measures included sparing at the lesion epicenter, sparing
      throughout the extent of the lesion, quantification of myelin loss rostral and
      caudal to the lesion, and motor neuron counts. Compared to controls, animals
      receiving SCI exhibited injury severity-specific deficits in forelimb, locomotor,
      and hindlimb function persisting for 6-weeks post-SCI. Histological analysis
      revealed ipsilateral containment of the injury, and differentiation between
      groups on all measures except motor neuron counts. This model has many
      advantages: (1) minimal animal care requirements post-SCI, (2) within subject
      controls, (3) functional loss involves primarily the ipsilateral forelimb, and
      (4) it is a behavioral and histological model for both gray and white matter
      damage caused by contusive SCI.

PMID- 16430372
TI  - Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a
      novel method for minimally invasive cell transplantation.
AB  - Cell transplantation as a treatment for spinal cord injury is a promising
      therapeutic strategy whose effective clinical application would be facilitated by
      non-invasive delivery protocols. Cells derived from the bone marrow are
      particularly attractive because they can be obtained easily, expanded to large
      numbers and potentially used for autologous as well as allogeneic
      transplantation. In this study we tested the feasibility of a novel minimally
      invasive method--lumbar puncture (LP)--for transplanting bone marrow stromal stem
      cells (MSC) into a clinically relevant spinal cord contusion model. We further
      sought to determine optimal protocols for performing such minimally invasive cell
      transplantation. Sprague-Dawley rats received a moderate contusion injury at the
      midthoracic level followed by LP transplantation of MSC derived from transgenic
      rats that express the human placental alkaline phosphatase (AP) reporter gene.
      The recipients were analyzed histologically to evaluate the extent of cell
      delivery and survival at the injury site. We found that MSC delivered by LP
      reached the contused spinal cord tissues and exerted a significant beneficial
      effect by reducing cyst and injury size. Transplantation within 14 days of injury
      provided significantly greater grafting efficiency than more delayed delivery,
      and increasing MSC dosage improved cell engraftment. The techniques described
      here can easily be translated to patients, thus accelerating clinical application
      of stem cell therapies.

PMID- 16430373
TI  - Combined treatment with neurotrophin-3 and LSD facilitates behavioral recovery
      from double-hemisection spinal injury in neonatal rats.
AB  - We explored functional recovery in two spinal cord injury models following a
      novel combination treatment (NT-3 + LSD). One group of rats received a staggered
      double hemisection (DH) at postnatal day 2 (P2) of the left hemicord at T11 and
      the right hemicord at T12. Another group received complete transection (CT) at
      T11 on P2. A third group was sham operated. Each of these groups was also treated
      with the drug combination. Drugs were administered intrathecally above the lesion
      during surgery, and again s.c. at P4, P6, P8, and P10. Intracellular recording in
      an in vitro spinal cord preparation at P10-P12 in DH rats revealed weak
      polysynaptic connections to lumbar motoneurons through the injury region, but
      only in those receiving NT-3 + LSD; NT-3 or LSD alone had no effect. In
      behavioral experiments, the frequency of rearing in an open field and hindlimb
      kicks during swimming was assessed every 3-4 days from P9 to P58. Both CT and DH
      injury severely impaired rearing and hindlimb kicking during swimming. DH rats
      treated with NT-3 + LSD showed significantly more kicks during swimming than
      untreated DH or CT rats and treated CT rats beginning as early as P9 and lasting
      through the duration of testing. Rearing behavior was also improved by treatment
      but beginning only in the 3rd postnatal week, the time at which it normally
      develops. Rearing frequency reached sham control levels by P40. Our results
      suggest this combination treatment may be a promising new strategy for
      facilitating recovery from moderate spinal cord injury.

PMID- 16430374
TI  - Understanding drug disposition alterations induced by acute spinal cord injury:
      role of injury level and route of administration for agents submitted to
      extensive liver metabolism.
AB  - It is known that acute spinal cord injury (SCI) produces hemodynamic alterations,
      including a reduction in liver blood flow that is more pronounced after high
      thoracic than after low-thoracic injury. To determine if these changes have an
      impact in the pharmacokinetics of high extraction drugs (i.e., those drugs which
      clearance mainly depends on liver blood flow), we studied the pharmacokinetics of
      a model compound, phenacetin, and of its main metabolite, acetaminophen, in rats
      24 h after a high (T1) or a low (T8) SCI, as well as in sham-lesioned controls.
      After intravenous administration to animals with SCI, reductions in drug
      clearance and distribution led to an increase in blood concentrations. These
      alterations were more pronounced after high than after low SCI, as expected from
      hemodynamic changes. After oral administration, phenacetin blood levels were
      similar in sham-lesioned and T1-injured animals, but decreased by injury at T8.
      This is likely due to a reduction in drug absorption which compensates the
      changes in distribution and elimination induced by injury at T1, whereas it
      prevails in T8-lesioned animals. Acetaminophen blood concentrations observed
      after intravenous or oral phenacetin, or after the oral administration of
      acetaminophen by itself, were increased or reduced, depending on the overall
      effect of the alterations on absorption, first pass metabolism, distribution and
      elimination induced by high and low SCI. Results demonstrate that acute SCI
      significantly alters the pharmacokinetics of high extraction drugs. The outcome
      of such alterations depends on the level of SCI and on the route of
      administration.

PMID- 16430376
TI  - Comparison of seven anesthetic agents on outcome after experimental traumatic
      brain injury in adult, male rats.
AB  - Isoflurane is commonly used in experimental traumatic brain injury (TBI), both
      before and early after injury, yet it is rarely used clinically. Narcotics and
      benzodiazepines are frequently used after injury in clinical TBI. We compared
      seven anesthetic/sedative agents applied after injury in the controlled cortical
      impact model: diazepam, fentanyl, isoflurane, ketamine, morphine, pentobarbital,
      and propofol. Our objective was to provide insight into the relative degrees of
      neuroprotection provided by these agents in a standard model of TBI. We
      hypothesized that the choice of anesthetic/sedative early after experimental TBI
      critically impacts outcome and that the agents most commonly used clinically may
      be less neuroprotective than isoflurane. Rats treated with isoflurane had the
      best cognitive recovery (p < 0.05) and hippocampal neuronal survival (p < 0.05).
      Conversely, rats treated with ketamine had the most hippocampal neuronal death (p
      < 0.05). Morphine or propofol, two agents commonly used clinically, were
      associated with the poorest motor function on post-trauma day 1-5 (p < 0.05). Our
      data support beneficial effects of isoflurane early after experimental TBI. Our
      data suggest that the early post-TBI use of isoflurane, despite practical
      logistical issues, could potentially provide clinical benefits in TBI--versus
      other commonly used sedatives or analgesics. Furthermore, the choice of post
      injury sedation and analgesia could have important implications on attempts to
      translate novel therapies from bench to field or bedside.

PMID- 16430375
TI  - Early, transient increase in complexin I and complexin II in the cerebral cortex
      following traumatic brain injury is attenuated by N-acetylcysteine.
AB  - Alteration of excitatory neurotransmission is a key feature of traumatic brain
      injury (TBI) in which extracellular glutamate levels rise. Although increased
      synaptic release of glutamate occurs at the injury site, the precise mechanism is
      unclear. Complexin I and complexin II constitute a family of cytosolic proteins
      involved in the regulation of neurotransmitter release, competing with the
      chaperone protein alpha-SNAP (soluble N-ethylmaleimide-sensitive factor
      attachment protein) for binding to the synaptic vesicle protein synaptobrevin as
      well as the synaptic membrane proteins SNAP-25 and syntaxin, which together form
      the SNAP receptor (SNARE) complex. Complexin I is predominantly a marker of
      axosomatic (inhibitory) synapses, whereas complexin II mainly labels axodendritic
      and axospinous synapses, the majority of which are excitatory. In order to
      examine the role of these proteins in TBI, we have studied levels of both
      complexins in the injured hemisphere by immunoblotting over a time period ranging
      from 6 h to 7 days following lateral fluid-percussion brain injury in the rat.
      Transient increases in the levels of complexin I and complexin II proteins were
      detected in the injured cerebral cortex 6 h following TBI. This increase was
      followed by a decrease of complexin I in the injured cortex and hippocampus, and
      a decrease in both complexins in the injured thalamus region at day 3 and day 7
      post-injury. The early, transient increase in the injured cortex was completely
      blocked by N-acetylcysteine (NAC) administered 5 min following trauma, suggesting
      an involvement of oxidative stress. Neuronal loss was also reduced in the injured
      hemisphere with post-TBI NAC treatment. Our findings suggest a dysregulation of
      both inhibitory and excitatory neurotransmission following traumatic injury that
      is responsive to antioxidant treatment. These alterations in complexin levels may
      also play an important role in neuronal cell loss following TBI, and thus
      contribute to the pathophysiology of cerebral damage following brain injury.

PMID- 16430377
TI  - Cyclosporin A disposition following acute traumatic brain injury.
AB  - Although the precise mechanism of action remains to be defined, Cyclosporin A
      (CsA) has demonstrated potential for neuroprotection in animal models. Predictive
      dosing strategies for CsA in acute traumatic brain injured (TBI) patients must
      account for the influence of the acute phase response on drug disposition. To
      characterize CsA pharmacokinetic parameters early following acute TBI, serial
      blood samples from patients enrolled into a Phase II dose-escalation trial were
      analyzed. Within eight hours of injury, thirty patients admitted with acute
      severe TBI were prospectively randomized into three cohorts (n = 8 CsA; n = 2
      placebo per cohort) in this dose-escalation trial. Patients received one of three
      doses (I = 0.625 mg/kg/dose; II = 1.25 mg/kg/dose; III = 2.5 mg/kg/dose) or
      placebo intravenously every 12 h for 72 h. Serial blood collection began prior to
      dose 1 and continued for 72 h following the completion of six doses. Whole blood
      concentrations were determined by high-performance liquid chromatography (HPLC)
      with ultraviolet (UV) detection. Pharmacokinetic parameters were determined for
      each patient by fitting the concentration-time profile to a two-compartmental
      model with first order elimination. Mean area under the curve and predicted
      maximal blood concentration increased with each dosing cohort (I = 9840
      h*microg/L, 398 microg/L; II = 18300 h*microg/L, 645 microg/L; III = 32500
      h*microg/L, 1300 microg/L). Whole blood clearance, steady state volume of
      distribution, and beta half-life were independent of dose and higher than
      published reports from other populations: 0.420 L/h/kg, 5.91 L/kg, and 17.3 h,
      respectively. These data show patients with acute severe TBI demonstrate a more
      rapid clearance and a larger distribution volume of CsA. Pharmacokinetic
      parameters derived from this study will guide dosing strategies for future
      prospective clinical trials evaluating CsA therapy following acute TBI.

PMID- 16430379
TI  - Telemedicine and e-Health for international medical issues.

PMID- 16430380
TI  - Telemedicine news.

PMID- 16430381
TI  - Telethinking with Yulun Wang, Ph.D. (Interview by Vicki Glaser).

PMID- 16430382
TI  - The Arizona Telemedicine Program.

PMID- 16430383
TI  - A modeled economic analysis of a digital tele-ophthalmology system as used by
      three federal health care agencies for detecting proliferative diabetic
      retinopathy.
AB  - The objective of this study was to compare, using a 12-month time frame, the cost
      effectiveness of a non-mydriatic digital tele-ophthalmology system (Joslin Vision
      Network) versus traditional clinic-based ophthalmoscopy examinations with pupil
      dilation to detect proliferative diabetic retinopathy and its consequences.
      Decision analysis techniques, including Monte Carlo simulation, were used to
      model the use of the Joslin Vision Network versus conventional clinic-based
      ophthalmoscopy among the entire diabetic populations served by the Indian Health
      Service, the Department of Veterans Affairs, and the active duty Department of
      Defense. The economic perspective analyzed was that of each federal agency. Data
      sources for costs and outcomes included the published literature, epidemiologic
      data, administrative data, market prices, and expert opinion. Outcome measures
      included the number of true positive cases of proliferative diabetic retinopathy
      detected, the number of patients treated with panretinal laser photocoagulation,
      and the number of cases of severe vision loss averted. In the base-case analyses,
      the Joslin Vision Network was the dominant strategy in all but two of the nine
      modeled scenarios, meaning that it was both less costly and more effective. In
      the active duty Department of Defense population, the Joslin Vision Network would
      be more effective but cost an extra 1,618 dollars per additional patient treated
      with panretinal laser photo-coagulation and an additional 13,748 dollars per
      severe vision loss event averted. Based on our economic model, the Joslin Vision
      Network has the potential to be more effective than clinic-based ophthalmoscopy
      for detecting proliferative diabetic retinopathy and averting cases of severe
      vision loss, and may do so at lower cost.

PMID- 16430385
TI  - Development of a compact home health monitor for telemedicine.
AB  - A compact and easy-to-use home health monitor was developed. A palm-size health
      monitor contained a finger probe as sensor unit. In the finger probe, light from
      a light emitting diode (LED) array was illuminated on a finger nail bed, and
      transmitted light was measured to obtain photoplethysmography (PPG) signals.
      Hematocrit, pulse, respiration rate, and saturated oxygen in arterial blood
      (SpO(2)) were measured simultaneously from PPGs using five different wavelengths:
      569, 660, 805, 904, and 975 nm. To predict hematocrit, a dedicated algorithm was
      used based on scattering theory of red blood cells using these wavelengths.
      Preliminary clinical tests showed that the achieved percent errors were +/- 8.2%
      for hematocrit when tested with 549 persons (N = 549). Digital filtering
      techniques were used to extract respiratory information from a single PPG signal.
      SpO(2) was predicted on the basis of the ratio of the wavelengths 660 nm and 940
      nm. The accuracies were within clinically acceptable errors. In addition, the
      compact home health monitor included a blood pressure monitoring unit. For
      convenient and simultaneous measurement with the other previously mentioned
      signals, blood pressure was measured on a finger. An air cuff was installed on
      the same finger where PPGs were measured. Achieved mean differences were +/- 3.8
      mmHg for systole and +/- 5.1 mmHg for diastole. One can use the palm-size monitor
      simply by inserting a finger into the home health monitor that is suitable for
      telemedicine.

PMID- 16430384
TI  - Web-integration PROAFTN methodology for acute leukemia diagnosis.
AB  - OBJECTIVE: To develop and test a web-based Clinical Decision Support System
      (CDSS) tool, which integrated a new fuzzy multiple criteria classification
      methodology named PROAFTN in acute leukemia (AL) diagnosis. METHODS: We have
      integrated a PROAFTN method and developed a web-based clinical decision support
      system using standard JSP, servlets, and XML technologies. All website data are
      database-driven; and the database system can handle data store, update, and
      retrieval instantly. Since the system was moved to a web server, we have started
      our experimental testing on 191 AL cases. RESULTS: The percentage of correct
      classification in this experimental testing was consistent with the proposed
      prototype. 96.4% of AL cases were correctly classified, proving that web
      integration can be a promising tool for dissemination of CDSS tools. We found our
      system to be robust and capable of deployment for referring physicians.
      CONCLUSIONS: Our experimental results suggest that the Internet has promise as a
      means for distribution of CDSS tools. This system will help to: 1) make a
      "virtual" diagnosis and to compare its performances with given clinical
      diagnosis; 2) exchange health information between physicians and hematologists at
      the location and time of need; 3) assist online learning and simulate cases for
      training practitioners; 4) implement a strict security and access control for
      transmission of electronic health data through the Internet. The method will not
      replace specialists, but was developed to assist biologist-hematologists and
      general practitioners remotely in making decisions on medical diagnosis.

PMID- 16430386
TI  - Web-based screening for diabetic retinopathy in a primary care population: the
      EyeCheck project.
AB  - The objective of this study was to evaluate the feasibility of ATA category 2 Web
      based screening for diabetic retinopathy in a primary care population in the
      Netherlands. A total of 1,676 patients in a primary care setting, with diabetes,
      without known diabetic retinopathy, and without previous screening by an
      ophthalmologist, were included between January 1 and December 31, 2003. Patients
      underwent a brief questionnaire and two field retinal photography. Photographs
      were independently read by two ophthalmologists. Outcome measures were
      gradability of the photographs, need for pharmacologic pupil dilation, assessment
      as suspect for presence of diabetic retinopathy, of neovascularization and of
      diabetic retinopathy, and agreement between graders. Of the population studied,
      11.3% of patients required pupil dilation, average transmission time of images
      was 73 sec, 12.0% of patients had ungradable photographs, 10.4% of the patients
      with gradable photographs were assessed as "suspect for diabetic retinopathy,"
      and 2.0% were assessed to need urgent referral. Red lesions were present in 3.5%
      and bright lesions were present in 1.6% of all gradable patients.
      Neovascularization of the disk was found in one patient. Type 1 patients had much
      higher rates of "suspect for diabetic retinopathy" (34.5%) than type 2 patients
      (9.4%). Interrater agreement kappa was 0.93. Web-based screening, using open
      source technology and uncompressed images, is feasible in a primary care setting,
      with a high rate of inter-rater agreement. Dilate-as-needed may be a sensible
      approach for retinal photography. The high incidence of "suspect for diabetic
      retinopathy" in type 1 diabetes patients illustrates that web-based diabetic
      retinopathy screening programs for these patients may detect diabetic retinopathy
      that would otherwise have gone undetected.

PMID- 16430387
TI  - Telemonitoring of medication adherence in patients with schizophrenia.
AB  - Nonadherence to medication is a widespread problem in schizophrenia and is
      associated with poor clinical outcomes and inappropriate management and
      utilization of resources. The aim of the current investigation was to assess the
      impact of telemonitoring of medication adherence on symptomatology and service
      use in patients with schizophrenia. A total of 108 schizophrenia patients were
      randomized into three equal groups according to the approaches used to assess
      medication adherence; self-report, pill counting, and telemonitoring.
      Telementoring was achieved through an innovative new platform called @HOME. This
      platform offers clinicians early warnings about impeding nonadherence as well as
      information about the pattern of medication taking. Patient's adherence was
      observed over an 8-week period, during which patient's clinical status and
      service use were recorded. In comparison to the other two groups, patients using
      @HOME showed improvement in the Global Clinical Impression Scale and a
      significant reduction in emergency visits and medical appointments. The @HOME
      platform was highly acceptable by patients, caregivers, and professionals, and
      required minimal training for implementation. The results of the study suggest
      that the use of telemonitoring in psychiatric settings was both feasible and
      acceptable and may be associated with significant clinical and service related
      benefits.

PMID- 16430388
TI  - What is missing on their web sites? An evaluation of national and international
      pharmaceutical companies in Turkey.
AB  - The Turkish Pharmaceutical Manufacturers Association-Ilac Endustrisi Isverenler
      Sendikasi (IEIS) set guidelines for pharmaceutical companies when designing their
      websites in 2003. The objective of this study is to evaluate whether
      pharmaceutical company websites comply with these guidelines. The list of all the
      national and international pharmaceutical companies active in Turkey is obtained
      from Farmalist Vademecum. We evaluated each site in terms of availability of drug
      advertisement, mail address, e-mail address, telephone number, fax number, update
      information, indication of target group, links, references, information,
      appropriate content for the intended target group, disclaimer stating the given
      information is only for health care professionals, disclaimer stating the given
      information cannot replace a health care professional, responsible body for the
      website design. The search was done throughout February 2005. We used x(2) test
      and Fisher's exact x(2) tests for statistical analysis. Of the 82 pharmaceutical
      companies active in Turkey, 51 had a website eligible for evaluation. Of the 51
      companies, 34 (66.7%) were national and 17 (33.3%) were international. Eighteen
      companies had drug advertisement on the home page of their websites (64.7%). Of
      the total companies majority had mail address (89.2%); telephone number (89.2%);
      fax number (84.3%); links (66.7%); and appropriate content for the health care
      professionals (62.7%). The frequency of having update information and a separate
      pharmacist/physician information part was higher among international
      pharmaceutical company websites compared to the national ones. These differences
      were statistically significant (p < 0.05). As a result of the evaluation, the
      majority of the pharmaceutical companies failed to comply wholly with the
      guidelines set by IEIS when designing their website on the Internet.

PMID- 16430389
TI  - Adaptive tele-application for remote neurology diagnosis.
AB  - This paper presents the Collaborative Tele-Neurology (TeNeCi) project which
      allows practitioners to use telecommunication technologies to provide medical
      information and services for neurological diseases. Specificities of remote
      neurology are described and the Cooperative Application Framework (CAliF)
      multimedia platform on which TeNeCi relies is presented. The technical
      requirements of such a project in terms of communication and consistency
      management, audio and video transmissions, and network support, as well as
      implementation of TeNeCi was evaluated. The software used in this application is
      composed of several services, such as a Digital Imaging and Communications in
      Medicine (DICOM) explorer, a DICOM viewer, and a security service. Tests
      performed on this first TeNeCi release showed good results, and allowed us to
      explore a larger collaborative experimentation between hospitals in France and
      Switzerland.

PMID- 16430390
TI  - Guiding users to quality information about osteoarthritis on the Internet: a
      pilot study.
AB  - This pilot study explored the feasibility of and user satisfaction with an
      Internet User's Guide (IUG) to assist patients in sourcing relevant, valid
      information about osteoarthritis on the Internet. Twelve people with
      osteoarthritis participated in focus groups that involved searching the Internet
      for information relating to their condition with the aid of the IUG. Participants
      were asked to perform an initial search of the Internet for information on
      osteoarthritis, followed by a second search with the aid of the IUG. User
      satisfaction with the IUG and subsequent online searches was obtained during and
      following the Internet simulations. A total of 92% of all participants had
      previously used the Internet to search for health information in the past.
      However, only a third used the Internet to further source information on their
      condition. Prior to using the IUG, participants cited efficiently searching the
      Internet for relevant and credible information as the primary obstacle in their
      continued use of the Internet. All participants reported that the use of the IUG
      increased their ability to source quality online medical information. The
      provision of an IUG may support and increase user awareness about searching for
      relevant, quality medical information on the Internet. Further quantitative and
      qualitative research is required to identify how best to empower consumers who
      wish to use the Internet as a medical resource.

PMID- 16430391
TI  - Designing home telecare: a case study in monitoring cystic fibrosis.
AB  - The objective of this study was to investigate the feasibility of using home
      telecare for monitoring cystic fibrosis (CF). Five adolescents were asked to use
      a home telecare system during a routine hospital visit over one week. Frequency
      of use was measured from computer logs. Unacceptable measurements were identified
      by visual inspection. User impressions of home telecare and appropriateness of
      the system for managing CF was determined from observations of user interaction,
      survey and qualitative analysis. Patients used the system to record lung function
      measurements without any supervision and indicated that the system was easy to
      learn and use. The role of home telecare in supporting collaborative self
      management appeared to be well understood. Home telecare was seen as a supplement
      to standard care that would provide a link to the hospital between clinic visits.
      Participants indicated that feedback provided by the system and ongoing clinical
      support would determine long-term use and compliance with the monitoring
      protocol. Clinicians reported the usefulness of home telecare in maintaining a
      longitudinal record of their patient's health that would supplement verbal
      description of symptoms and reduce time to treatment by increasing patient self
      awareness of health status. Home telecare may be a feasible intervention for
      monitoring CF. Feedback provided by the system must be presented in a format that
      is familiar and easily understood by users. Further system refinement and
      evaluation is required to determine patient compliance with their customized
      monitoring protocol prior to assessing impact on clinical outcomes.

PMID- 16430393
TI  - The challenge of early breast cancer detection among immigrant and minority women
      in multicultural societies.
AB  - A sociological view of the barriers experienced by women from traditional
      cultures, both in their native countries and as immigrants and minorities in
      multicultural western societies, in preventive health care generally and in
      breast screening specifically, is essential not only to understand patterns of
      late-stage diagnosis, but also to design successful interventions and programs.
      Breast cancer is a unique disease, as its name ties together a multisymbolic
      organ of the female anatomy and a potentially fatal affliction, the treatment of
      which commonly is a body-mutilating procedure (mastectomy). Because of its
      special nature, breast cancer is shrouded in fears, myths, and connotations
      reaching far beyond the objective clinical understanding of the disease. Many
      women do not use available breast-screening services and present with advanced
      symptoms. To help women detect and treat breast cancer early, health care
      providers and policymakers should try to understand their predicaments and the
      factors influencing their decisions. Structural barriers include such
      socioeconomic factors as poor health insurance, distance to medical facilities,
      and inability to take time off from work, while organizational barriers include
      difficulty in navigating complex health care systems and interacting with medical
      staff. Psychological and sociocultural barriers include poor health motivation,
      denial of personal risk, fatalism, mistrust of cancer treatments, and the fear of
      becoming a burden on family members. These barriers can often preclude proactive
      breast screening or rapid response to symptoms, even when breast cancer awareness
      is rather high. Moreover, in many traditional societies, especially Muslim ones,
      women's decisions and actions are controlled by men, and men may be unaware of or
      disapprove of breast screening. This article discusses several approaches to
      lowering the described barriers, including specially tailoring educational
      programs that dispel cancer myths, involving men in breast cancer detection
      efforts, implementing cultural competence training for mainstream health care
      providers, and recruiting minority health care professionals to enable better
      outreach to their coethnics.

PMID- 16430394
TI  - Experiences of breast cancer survivor-advocates and advocates in countries with
      limited resources: a shared journey in breast cancer advocacy.
AB  - The last decade has been marked by rapid growth in the breast cancer advocacy
      movement around the world. Today such movements are well established in North
      America and western Europe, and are emerging and gaining momentum in regions of
      the world with limited resources--Africa, Asia, eastern Europe, and Latin
      America. Internationally breast cancer advocates have faced the challenges of
      dealing with many languages, cultures, countries, and health systems. Because of
      these differences, existing models of breast cancer advocacy are not always
      appropriate or reproducible across countries. At the second biennial Global
      Summit Consensus Conference on International Breast Health Care, 12 breast cancer
      survivor-advocates and advocates from around the world gave statements describing
      the experiences of women with breast cancer and with advocacy in their countries,
      and attended a roundtable meeting to discuss breast cancer advocacy from a global
      perspective. We used the "long table" method to analyze their comments and
      identify common experiences. Although participants came from diverse settings,
      the analysis revealed five common experiences that were consistent across
      cultures: 1) the experiences and fears of breast cancer survivors, 2) beliefs and
      taboos about breast cancer that hinder awareness programs and treatment, 3) the
      need for public education and breast cancer awareness programs in countries with
      limited resources, 4) difficulty in translating the concept and ethos of advocacy
      into many languages, and 5) the experiences in establishing and maintaining
      advocacy groups to promote breast cancer awareness and to inform public policy.
      These themes constitute an action agenda for breast cancer advocacy groups in
      countries with limited resources. In addition, they provide invaluable insight
      for policymakers, program planners, and others undertaking efforts to improve
      breast cancer outcomes in low-resource settings.

PMID- 16430395
TI  - Breast cancer in limited-resource countries: early detection and access to care.
AB  - Although incidence, mortality, and survival rates vary fourfold in the world's
      regions, in the world as a whole, the incidence of breast cancer is increasing,
      and in regions without early detection programs, mortality is also increasing.
      The growing burden of breast cancer in low-resource countries demands adaptive
      strategies that can improve on the too common pattern of disease presentation at
      a stage when prognosis is very poor. In January 2005, the Breast Health Global
      Initiative (BHGI) held its second summit in Bethesda, MD. The Early Detection and
      Access to Care Panel reaffirmed the core principle that a requirement at all
      resource levels is that women should be supported in seeking care and should have
      access to appropriate, affordable diagnostic tests and treatment. In terms of
      earlier diagnosis, the panel recommended that breast health awareness should be
      promoted to all women. Enhancements to basic facilities might include the
      following, in order of resources: effective training of relevant staff in
      clinical breast examination (CBE) both for symptomatic and asymptomatic women;
      opportunistic screening with CBE; demonstration projects or trials of organized
      screening using CBE or breast self-examination; and finally, feasibility studies
      of mammographic screening. Ideally, for complete evaluation, such projects
      require notification of deaths among breast cancer cases and staging of diagnosed
      tumors.

PMID- 16430396
TI  - Breast cancer in limited-resource countries: diagnosis and pathology.
AB  - In 2002 the Breast Health Global Initiative (BHGI) convened a panel of breast
      cancer experts and patient advocates to develop consensus recommendations for
      diagnosing breast cancer in countries with limited resources. The panel agreed on
      the need for a pathologic diagnosis, based on microscopic evaluation of tissue
      specimens, before initiating breast cancer treatment. The panel discussed options
      for pathologic diagnosis (fine-needle aspiration biopsy, core needle biopsy, and
      surgical biopsy) and concluded that the choice among these methods should be
      based on available tools and expertise. Correlation of pathology, clinical, and
      imaging findings was emphasized. A 2005 BHGI panel reaffirmed these
      recommendations and additionally stratified diagnostic and pathology methods into
      four levels--basic, limited, enhanced, and maximal--from lowest to highest
      resources. The minimal requirements (basic level) include a history, clinical
      breast examination, tissue diagnosis, and medical record keeping. Fine-needle
      aspiration biopsy was recognized as the least expensive reliable method of tissue
      sampling, and the need for comparing its clinical usefulness with that of core
      needle biopsy in the limited-resource setting was emphasized. Increasing
      resources (limited level) may enable diagnostic breast imaging (ultrasound +/-
      mammography), use of tests to evaluate for metastases, limited image-guided
      sampling, and hormone receptor testing. With more resources (enhanced level),
      diagnostic mammography, bone scanning, and an onsite cytologist may be possible.
      Mass screening mammography is introduced at the maximal-resource level. At all
      levels, increasing breast cancer awareness, diagnosing breast cancer at an early
      stage, training individuals to perform and interpret breast biopsies, and
      collecting statistics about breast cancer, resources, and competing priorities
      may improve breast cancer outcomes in countries with limited resources. Expertise
      in pathology was reaffirmed to be a key requirement for ensuring reliable
      diagnostic findings. Several approaches were again proposed for improving breast
      pathology, including training pathologists, establishing pathology services in
      centralized facilities, and organizing international pathology services.

PMID- 16430397
TI  - Breast cancer in limited-resource countries: an overview of the Breast Health
      Global Initiative 2005 guidelines.
AB  - Breast cancer is the most common cause of cancer-related death among women
      worldwide, with case fatality rates highest in low-resource countries. Despite
      significant scientific advances in its management, most of the world faces
      resource constraints that limit the capacity to improve early detection,
      diagnosis, and treatment of the disease. The Breast Health Global Initiative
      (BHGI) strives to develop evidence-based, economically feasible, and culturally
      appropriate guidelines that can be used in nations with limited health care
      resources to improve breast cancer outcomes. Using an evidence-based consensus
      panel process, four BHGI expert panels addressed the areas of early detection and
      access to care, diagnosis and pathology, treatment and resource allocation, and
      health care systems and public policy as they relate to breast health care in
      limited-resource settings. To update and expand on the BHGI Guidelines published
      in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health
      care improvement using a tiered system of resource allotment into four levels
      basic, limited, enhanced, and maximal-based on the contribution of each resource
      toward improving clinical outcomes. Early breast cancer detection improves
      outcome in a cost-effective fashion assuming treatment is available, but requires
      public education to foster active patient participation in diagnosis and
      treatment. Clinical breast examination combined with diagnostic breast imaging
      (ultrasound +/- diagnostic mammography) can facilitate cost-effective tissue
      sampling techniques for cytologic or histologic diagnosis. Breast-conserving
      treatment with partial mastectomy and radiation therapy requires more health care
      resources and infrastructure than mastectomy, but can be provided in a
      thoughtfully designed limited-resource setting. The availability and
      administration of systemic therapies are critical to improving breast cancer
      survival. Estrogen receptor testing allows patient selection for hormonal
      treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some
      allocation of resources and infrastructure, is needed to treat node-positive,
      locally advanced breast cancers, which represent the most common clinical
      presentation of disease in low-resource countries. When chemotherapy is not
      available, patients with locally advanced, hormone receptor-negative cancers can
      only receive palliative therapy. Future research is needed to better determine
      how these guidelines can best be implemented in limited-resource settings.

PMID- 16430398
TI  - Breast cancer in limited-resource countries: treatment and allocation of
      resources.
AB  - Treating breast cancer under the constraints of significantly limited health care
      resources poses unique challenges that are not well addressed by existing
      guidelines. We present evidence-based guidelines for systematically prioritizing
      cancer therapies across the entire spectrum of resource levels. After
      consideration of factors affecting the value of a given breast cancer therapy
      (contribution to overall survival, disease-free survival, quality of life, and
      cost), we assigned each therapy to one of four incremental levels--basic,
      limited, enhanced, or maximal--that together map out a sequential and flexible
      approach for planning, establishing, and expanding breast cancer treatment
      services. For stage I disease, basic-level therapies are modified radical
      mastectomy and endocrine therapy with ovarian ablation or tamoxifen; therapies
      added at the limited level are breast-conserving therapy, radiation therapy, and
      standard-efficacy chemotherapy (cyclophosphamide, methotrexate, and 5
      fluorouracil [CMF], or doxorubicin and cyclophosphamide [AC], epirubicin and
      cyclophosphamide [EC], or 5-fluorouracil, doxorubicin, and cyclophosphamide
      [FAC]); at the enhanced level, taxane chemotherapy and endocrine therapy with
      aromatase inhibitors or luteinizing hormone-releasing hormone (LH-RH) agonists;
      and at the maximal level, reconstructive surgery, dose-dense chemotherapy, and
      growth factors. For stage II disease, the therapy allocation is the same, with
      the exception that standard-efficacy chemotherapy is a basic-level therapy. For
      locally advanced breast cancer, basic-level therapies are modified radical
      mastectomy, neoadjuvant chemotherapy (CMF, AC, or FAC), and endocrine therapy
      with ovarian ablation or tamoxifen; the therapy added at the limited level is
      postmastectomy radiation therapy; at the enhanced level, breast-conserving
      therapy, breast-conserving whole-breast radiation therapy, taxane chemotherapy,
      and endocrine therapy with aromatase inhibitors or LH-RH agonists; and at the
      maximal level, reconstructive surgery and dose-dense chemotherapy and growth
      factors. For metastatic or recurrent disease, basic-level therapies are total
      mastectomy for ipsilateral in-breast recurrence, endocrine therapy with ovarian
      ablation or tamoxifen, and analgesics; therapies added at the limited level are
      radiation therapy and CMF or anthracycline chemotherapy; at the enhanced level,
      chemotherapy with taxanes, capecitabine, or trastuzumab, endocrine therapy with
      aromatase inhibitors, and bisphosphonates; and at the maximal level, chemotherapy
      with vinorelbine, gemcitabine, or carboplatin, growth factors, and endocrine
      therapy with fulvestrant. Compared with the treatment of early breast cancer, the
      treatment of advanced breast cancer is more resource intensive and generally has
      poorer outcomes, highlighting the potential benefit of earlier detection and
      diagnosis, both in terms of conserving scarce resources and in terms of reducing
      morbidity and mortality. Use of the scheme outlined here should help ministers of
      health, policymakers, administrators, and institutions in limited-resource
      settings plan, establish, and gradually expand breast cancer treatment services
      for their populations.

PMID- 16430399
TI  - Breast cancer in limited-resource countries: health care systems and public
      policy.
AB  - As the largest cancer killer of women around the globe, breast cancer adversely
      impacts countries at all levels of economic development. Despite major advances
      in the early detection, diagnosis, and treatment of breast cancer, health care
      ministries face multitiered challenges to create and support health care programs
      that can improve breast cancer outcomes. In addition to the financial and
      organizational problems inherent in any health care system, breast health
      programs are hindered by a lack of recognition of cancer as a public health
      priority, trained health care personnel shortages and migration, public and
      health care provider educational deficits, and social barriers that impede
      patient entry into early detection and cancer treatment programs. No perfect
      health care system exists, even in the wealthiest countries. Based on inevitable
      economic and practical constraints, all health care systems are compelled to make
      trade-offs among four factors: access to care, scope of service, quality of care,
      and cost containment. Given these trade-offs, guidelines can define stratified
      approaches by which economically realistic incremental improvements can be
      sequentially implemented within the context of resource constraints to improve
      breast health care. Disease-specific "vertical" programs warrant "horizontal"
      integration with existing health care systems in limited-resource countries. The
      Breast Health Global Initiative (BHGI) Health Care Systems and Public Policy
      Panel defined a stratified framework outlining recommended breast health care
      interventions for each of four incremental levels of resources (basic, limited,
      enhanced, and maximal). Reallocation of existing resources and integration of a
      breast health care program with existing programs and infrastructure can
      potentially improve outcomes in a cost-sensitive manner. This adaptable framework
      can be used as a tool by policymakers for program planning and research design to
      make best use of available resources to improve breast health care in a given
      limited-resource setting.

PMID- 16430400
TI  - Use of statistics to assess the global burden of breast cancer.
AB  - A variety of statistics are used to quantify the burden (occurrence and outcome)
      of cancer generally and of breast cancer specifically. When undertaking any
      cancer control program, understanding these statistics, their source, and their
      quality is important for assessing the current situation, allocating resources to
      different control strategies, and evaluating progress. Two core statistics are
      the cancer incidence rate and the cancer mortality rate, which provide estimates
      of the average risk of acquiring and of dying from the disease, respectively.
      About 16% of the world's population is covered by registration systems that
      produce cancer incidence statistics, while mortality data are available for about
      29%. Breast cancer incidence and mortality vary considerably by world region. In
      general, the incidence is high (greater than 80 per 100,000) in developed regions
      of the world and low (less than 30 per 100,000), though increasing, in developing
      regions; the range of mortality rates is much less (approximately 6-23 per
      100,000) because of the more favorable survival of breast cancer in (high
      incidence) developed regions. The incidence of breast cancer is increasing almost
      everywhere. This unfavorable trend is due in part to increases in risk factors
      (decreased childbearing and breast-feeding, increased exogenous hormone exposure,
      and detrimental dietary and lifestyle changes, including obesity and less
      physical activity). On the other hand, mortality is now decreasing in many high
      risk countries due to a combination of intensified early detection efforts and
      the introduction of mammographic screening, resulting in the diagnosis of more
      small, early stage tumors, and advances in treatment.

PMID- 16430402
TI  - Tumor size and breast cancer detection: what might be the effect of a less
      sensitive screening tool than mammography?
AB  - In some limited-resource areas, a state-of-the-art mammography program is not
      affordable. In such circumstances, one might consider a less resource-intensive,
      but also less sensitive screening tool such as clinical breast examination (CBE).
      We used data from the Swedish Two-County Trial to estimate the shift in tumor
      size resulting from invitation to mammographic screening. By postulating a lesser
      benefit of a less sensitive screening tool (CBE), particularly in terms of
      detecting very small tumors, we predicted its likely effect on tumor size
      distribution. In addition, using the observed association between tumor size and
      nodal status, and between tumor size and fatality, we predicted the likely
      benefit in terms of reductions in node-positive disease and in breast cancer
      mortality. An invitation to mammographic screening was associated with a 27%
      reduction in the number of node-positive tumors and a 31% reduction in the number
      of breast cancer deaths. We estimate that in the trial population, screening with
      CBE alone would have led to an 11% reduction in node-positive tumors and an 11%
      reduction in breast cancer deaths (approximately 42 deaths prevented per 1,000
      cases). Assuming instead a tumor size distribution typical of a limited-resource
      setting (70% of tumors are 30 mm at presentation), we estimate that screening
      with CBE alone would lead to a 13% reduction in node-positive tumors and a 12%
      reduction in breast cancer deaths (approximately 72 deaths prevented per 1,000
      cases). Thus, although the relative benefit of CBE is only slightly greater in
      the limited-resource setting, the absolute reduction in deaths per case is about
      70% higher. Our findings suggest that a less sensitive tool might be expected to
      confer a breast cancer mortality reduction about half of that observed with
      mammography.

PMID- 16430401
TI  - Costs and health effects of breast cancer interventions in epidemiologically
      different regions of Africa, North America, and Asia.
AB  - We estimated the costs and health effects of treating stage I, II, III, and IV
      breast cancer individually, of treating all stages, and of introducing an
      extensive cancer control program (treating all stages plus early stage diagnosis)
      in three epidemiologically different world regions--Africa, North America, and
      Asia. We developed a mathematical simulation model of breast cancer using the
      stage distribution and case fatality rates in the presence and absence of
      treatment as predictors of survival. Outcome measures were life-years adjusted
      for disability (DALYs), costs (in 2000 U.S. dollars) of treatment and follow-up,
      and cost-effectiveness ratios (CERs; in dollars per DALY averted). Sensitivity
      analyses were performed to determine the robustness of the results. Treating
      patients with stage I breast cancer resulted in 23.41, 12.25, and 19.25 DALYs
      averted per patient in Africa, North America, and Asia, respectively. The
      corresponding average CERs compared with no intervention were 78 U.S. dollars ,
      1,960 U.S. dollars, and 62 U.S. dollars per DALY averted. The number of DALYs
      averted per patient decreased with stage; the value was lowest for stage IV
      treatment (0.18-0.19), with average CERs of 4,986 U.S. dollars in Africa, 70,380
      U.S. dollars in North America, and 3,510 U.S. dollars per DALY averted in Asia.
      An extensive breast cancer program resulted in 16.14, 12.91, and 12.58 DALYs
      averted per patient and average CERs of 75 U.S. dollars, 915 U.S. dollars, and 75
      U.S. dollars per DALY averted. Outcomes were most sensitive to case fatality
      rates for untreated patients, but varying model assumptions did not change the
      conclusions. These findings suggest that treating stage I disease and introducing
      an extensive breast cancer program are the most cost-effective breast cancer
      interventions.

PMID- 16430404
TI  - Muscular dystrophy, anesthesia and the safety of inhalational agents revisited;
      again.

PMID- 16430403
TI  - Radiotherapy for breast cancer in countries with limited resources: program
      implementation and evidence-based recommendations.
AB  - Radiotherapy is an essential part of the multimodality treatment of breast
      cancer. Applying safe and effective treatment requires appropriate facilities,
      staff, and equipment, as well as support systems, initiation of treatment without
      undue delay, geographic accessibility, and completion of radiotherapy without
      undue prolongation of the overall treatment time. Radiotherapy can be delivered
      with a cobalt-60 unit or a linear accelerator (linac). In early stage breast
      cancer, radiotherapy is an integral part of breast-conserving treatment. Standard
      treatment includes irradiation of the entire breast for several weeks, followed
      by a boost to the tumor bed in women age 50 years or younger or those with close
      surgical margins. Mastectomy is an appropriate treatment for many patients.
      Postmastectomy irradiation with proper techniques substantially decreases local
      recurrences and improves survival in patients with positive axillary lymph nodes.
      It is also considered for patients with negative nodes if they have multiple
      adverse features such as a primary tumor larger than 2 cm, unsatisfactory
      surgical margins, and lymphovascular invasion. Many patients present with locally
      advanced or inoperable breast cancer. Their initial treatment is by systemic
      therapy; after responding to systemic therapy, most will require a modified
      radical mastectomy followed by radiotherapy. For those patients in whom
      mastectomy is still not possible after initial systemic therapy, breast and
      regional irradiation is given, followed whenever possible by mastectomy. For
      patients with distant metastases, irradiation may provide relief of symptoms such
      as pain, bleeding, ulceration, and lymphedema. A single fraction of irradiation
      can effectively relieve pain from bone metastases. Radiotherapy is also effective
      in the palliation of symptoms secondary to metastases in the brain, lungs, and
      other sites. Radiotherapy is important in the treatment of women with breast
      cancer of all stages. In developing countries, it is required for almost all
      women with the disease and should therefore be available.

PMID- 16430405
TI  - Developmental changes of pharyngeal airway patency: implications for pediatric
      anesthesia.

PMID- 16430406
TI  - Anesthesia and periinterventional morbidity of rigid bronchoscopy for
      tracheobronchial foreign body diagnosis and removal.
AB  - BACKGROUND: Undiagnosed tracheobronchial foreign body aspiration (FBA) or delayed
      extraction can lead to serious morbidity. The aim of this study was to evaluate
      anesthetic and periinterventional morbidity of a straightforward regime using
      rigid bronchoscopy to rule out or remove a tracheobronchial foreign body in
      children with suspicion of FBA. METHODS: We retrospectively analyzed rigid
      bronchoscopy charts of children with suspicion of acute (< or = 24 h) and
      subacute (>24 h-2 weeks) tracheobronchial FBA (1990-2003). Patient
      characteristics, duration of fasting, technique/course of anesthesia induction,
      and duration/course of rigid bronchoscopy were taken. Anesthetic,
      periinterventional complications and length of hospital stay were noted. Data are
      given in median (range [interquartile range]). RESULTS: A total of 287 children
      were included in this study. Median age was 1.7 years (0.2-14.2 [1.2-2.5]); in
      72.1% a tracheobronchial foreign body was found and removed. Fasting time before
      induction of anesthesia was 5 h (1-14 [4.0-7.0]). Anesthesia adverse events were
      seen in 0.7%, whereas periinterventional complication from rigid bronchoscopy was
      observed in 7.6%. Hospital discharge within 4 h after bronchoscopy was possible
      in 65.2%. Complications of delayed diagnosis (>24 h) were prolonged duration of
      rigid bronchoscopy because of severe mucosal changes or difficulties in foreign
      body extraction. CONCLUSIONS: General anesthesia for rigid bronchoscopy to rule
      out a tracheobronchial foreign body in children carries low morbidity. Most of
      the complications originated from the foreign body itself especially in patients
      with late diagnosis. The risk for serious complications caused by retained
      foreign bodies outweighs the low morbidity of explorative rigid bronchoscopy in
      children with suspected FBA or children with prolonged cough or pulmonary
      infection unresponsive to medical treatment.

PMID- 16430407
TI  - A technique to improve the safety of laryngeal mask airway when used in lacrimal
      duct surgery.
AB  - BACKGROUND: Congenital obstruction of the lacrimal drainage system is present in
      approximately 6% of newborn. Syringing and probing is one of the common
      interventional modalities for this condition. Current literature states that
      syringing and probing is performed best with general anesthesia with tracheal
      intubation. We study a technique to improve the safety and efficacy of the
      laryngeal mask airway (LMA) in lacrimal duct surgery. METHODS: Sixty-five ASA
      grade I-II patients between 6 months and 10 years scheduled for syringing and
      probing were included after informed consent was obtained from the parents. After
      induction of anesthesia and confirmation of LMA position, a transparent suction
      catheter was inserted into the hypopharynx. Continuous suction was applied to the
      catheter. A total of 2-3 ml of 0.01% povidone-iodine solution was used for
      syringing. Staining of the catheter was regarded as a sign of patency of the
      duct. RESULTS: None of our patients had perioperative airway or respiratory
      complications. CONCLUSIONS: Based on the results of our study, we suggest that
      the LMA can safely be used in lacrimal duct procedures. Using 0.01% povidone
      iodine as irrigation fluid further increases the margin of safety.

PMID- 16430408
TI  - Comparison of 'whoosh' and modified 'swoosh' test for identification of the
      caudal epidural space in children.
AB  - BACKGROUND: Caudal analgesia is widely used in pediatric anesthesia practice. The
      'whoosh' test which uses air to identify the epidural space, has been recommended
      as a guide for successful needle placement. However, the use of air may be
      associated with an incidence of neurological complications. The 'swoosh' test
      avoids the injection of air and was originally performed using injection of a
      local anesthetic solution. A comparison was made between the 'whoosh' test and a
      modified 'swoosh' test using saline to identify the caudal epidural space in
      children. METHODS: We studied 60 children of either sex in the age group of 2-8
      years undergoing inguinal herniotomy. During insertion of the caudal block, a
      stethoscope was placed over the lower lumbar spine to note the presence or
      absence of 'whoosh' or 'swoosh', by an independent observer who was blinded to
      the injection of 1 ml of air or saline which was given simultaneously by the
      operator into the caudal space. The operator's clinical impression of successful
      insertion of the needle was also recorded and correlated with the presence or
      absence of 'whoosh' or 'swoosh'. In addition, the need for supplemental
      intraoperative analgesia was noted. RESULTS: Overall success rate of caudal block
      using the 'whoosh' and modified 'swoosh' tests was found to be 96.6% and 93.3%,
      respectively as judged by the lack of supplementary perioperative analgesia. The
      sensitivity, specificity and positive predictive value of the 'whoosh' test and
      clinical predictors of caudal placement was found to be 100% whereas the modified
      'swoosh' test had a sensitivity of 93%, specificity of 50% and a positive
      predictive value of 96%. However, statistically there was no significant
      difference between the clinical predictors, 'whoosh' and the modified 'swoosh'
      test for identification of the caudal epidural space. CONCLUSIONS: The modified
      'swoosh' test is as reliable as the 'whoosh' test and we recommend it for
      identification of the caudal epidural space in children as it avoids injection of
      air into the caudal space.

PMID- 16430409
TI  - Comparison of cuffed, uncuffed tracheal tubes and laryngeal mask airways in low
      flow pressure controlled ventilation in children.
AB  - BACKGROUND: The use of low flow circle systems necessitates a 'leak free'
      breathing system which is commonly achieved by using a cuffed tracheal tube (TT).
      We hypothesized that low flow circle system anesthesia can equally effectively be
      achieved by using the LMA in pediatric anesthesia. METHODS: Following local
      ethics committee approval we randomly recruited 45 patients scheduled for
      elective surgery and requiring mechanical ventilation into three groups (cuffed
      TT, uncuffed TT and LMA group, n = 15). The size of the TT was determined by
      means of the formula (age/4) + 4.5 for uncuffed and (age/4) + 4 for cuffed TT
      whereas the size of the LMA size was dependent on weight. Following induction of
      anesthesia and muscle paralysis patients were ventilated with pressure controlled
      ventilation through a pediatric circle system and the lowest fresh gas flow (FGF)
      determined. RESULTS: The FGF achieved were (median and range) 0.20 (0.2-0.25)
      l.min(-1) for the LMA group, 0.20 (0.2-0.4) l.min(-1) for the cuffed TT group and
      1.15 (0.2-4.75) l.min(-1) for the uncuffed group. The differences between the LMA
      and cuffed TT compared with the uncuffed TT were significant (P < 0.0001 and P =
      0.0002, respectively). The difference in FGF between LMA and cuffed TT was not
      significant. CONCLUSION: We conclude that pressure controlled ventilation using
      an LMA is an alternative to a cuffed TT during low flow circle system anesthesia
      in children. Low FGF is unlikely to be achieved consistently using an uncuffed TT
      because of a substantial leak.

PMID- 16430410
TI  - Psychological predictors of postoperative sleep in children undergoing outpatient
      surgery.
AB  - BACKGROUND: The purpose of this study was to examine psychological predictors of
      postoperative sleep in children undergoing outpatient surgery. METHODS: We used
      hierarchical multivariate regression to examine the impact of demographic and
      personality variables such as parental worry/anxiety [NEO-personality inventory,
      revised (NEO-PI-R) Neuroticism], parental coping style (Miller Behavioral Style
      Scale), children's aggressive behavior [child behavior checklist (CBCL)
      externalizing], and children's temperament (emotionality, activity, sociability,
      and impulsivity) on postoperative sleep in 52 consecutive, healthy, children
      undergoing outpatient surgery. Sleep was assessed using actigraphy, a valid,
      reliable and objective measure of sleep quality. All perioperative protocols were
      strictly controlled and standardized. RESULTS: We found that 22% of the children
      experienced difficulty with postoperative sleep as defined by actigraphy. A
      hierarchical multiple regression model that was constructed to identify
      predictors of postoperative sleep efficiency in children accounted for 82% of the
      variance (R = 0.906, F = 19.42, P = 0.0001). Significant predictors in this model
      included preoperative sleep patterns (60%), postoperative pain (8.2%), parental
      anxiety/worry (NEO-PI-R Neuroticism scale; 9%), and children's aggressive
      behavior (CBCL externalizing; 5%). CONCLUSIONS: We conclude that psychological
      factors such as parental anxiety/worry and children's aggressive behavior are
      predictive of children's postoperative sleep above and beyond the influence of
      preoperative sleep patterns and postoperative pain.

PMID- 16430411
TI  - Postoperative morphine consumption in children with sickle-cell disease.
AB  - BACKGROUND: Effective pain control is a primary goal in the perioperative
      management of patients with sickle-cell disease. To understand analgesic
      requirements better, the authors compared postoperative morphine consumption and
      pain scores in sickle and non-sickle children who had undergone laparoscopic
      cholecystectomy. METHODS: We reviewed the medical records of all sickle and non
      sickle children referred to the Acute Pain Service of a tertiary care teaching
      hospital for patient-controlled analgesia (PCA) following laparoscopic
      cholecystectomy from 1996 to 2003. Data collected included postoperative morphine
      consumption, visual analogue pain scores, and perioperative outcome. RESULTS:
      Total postoperative morphine consumption in sickle children (n = 12) (1.58 +/-
      0.78 mg.kg(-1)) was more than double when compared with non-sickle children (n =
      10) (0.65 +/- 0.32 mg.kg(-1)) (P < 0.005). Duration of PCA use among sickle
      children (51 +/- 25 h) was more than double when compared with non-sickle
      children (21 +/- 11 h) (P < 0.005). Sickle patients had greater pain scores in
      the initial 24 h after surgery (P < 0.05) and used more adjuvant analgesics (P <
      0.05). Duration of postoperative hospital stay was 3.4 +/- 1.6 days and 1.5 +/-
      0.5 days for sickle and non-sickle children, respectively (P < 0.005).
      CONCLUSIONS: Sickle children self-administered more than double the amount of
      morphine, reported more intense pain, and remained hospitalized for more than
      twice as long as nonsickle children undergoing the same surgical procedure. These
      findings probably have a multifactorial origin, and might be attributable in part
      to alterations in pain perception, opioid pharmacokinetics, opioid tolerance, and
      psychosocial variables.

PMID- 16430412
TI  - Comparison of caudal ketamine with lidocaine or tramadol administration for
      postoperative analgesia of hypospadias surgery in children.
AB  - BACKGROUND: This study was designed to investigate whether the addition of
      tramadol or lidocaine to ketamine would enhance the quality of intra- and
      postoperative analgesia for hypospadias surgery in children. METHODS: Sixty-two
      ASA PS I or II children, between 1 and 10 years of age, scheduled for hypospadias
      surgery were recruited. Anesthesia was induced with 6-8% sevoflurane and
      maintained with 0.5-2.5% sevoflurane-50% N2O in oxygen. Children were allocated
      randomly to receive one of two study drugs. Children in group KL received caudal
      ketamine (0.25 mg.kg(-1)) plus lidocaine (2%, 2 mg.kg(-1)) and in group KT
      ketamine (0.25 mg.kg(-1)) plus tramadol (1 mg.kg(-1)). Systemic blood pressure,
      heart rate, peripheral O2 saturation, sedation, and pain scores (CHEOPS) were
      recorded at 1, 5, 10, 15, 30, 45 min and 1, 2, 3 h following recovery from
      anesthesia. RESULTS: Duration of analgesia was similar in the two groups (P >
      0.05). CHEOPS in group KL was lower than in group KT during the study period,
      except at first 15 min. Sedation scores were higher in group KL than group KT in
      the first 10 min (P < 0.05). Incidence of postoperative nausea and vomiting was
      similar in the two groups (P > 0.05) Sevoflurane concentration required was
      significantly lower in group KL than group KT peroperatively (P < 0.001).
      CONCLUSIONS: Caudal ketamine (0.25 mg.kg(-1)), plus lidocaine (2% 2 mg.kg(-1))
      significantly reduced sevoflurane concentration compared with ketamine (0.25
      mg.kg(-1)) + tramadol (1 mg.kg(-1)). We suggested that both ketamine + lidocaine
      and ketamine + tramadol provided very effective and long duration of analgesia,
      similarly. However, analgesia quality is superior in the ketamine-lidocaine group
      postoperatively.

PMID- 16430413
TI  - Perception of pain following rectal administration of morphine in children: a
      comparison of a gel and a solution.
AB  - BACKGROUND: Rectal administration of morphine is one possible route of delivery
      in children. The aim of this study was to determine the pain experience during
      rectal administration of two different morphine preparations. METHODS: The
      acceptance of the pain of rectal administration of morphine for premedication was
      studied in 120 children. Children were randomized to receive either morphine
      solution in saline (0.2 mg.kg(-1), 1 mg.ml(-1)) or morphine gel (0.2 mg.kg(-1), 1
      mg.ml(-1)) with an adjusted pH for rectal use in a double-blind fashion. Children
      were stratified into three groups according to age (1-2, 3-6, and 7-10 years).
      Pain was assessed with the Children's Hospital of Eastern Ontario Pain Scale, the
      McGrath Facial Affective Scale, or the visual analogue scale, depending on the
      age group. RESULTS: The overall pain scores in all age groups were low. Children
      aged 1-2 years (P < 0.01) and 3-6 years (P < 0.05) had significantly less pain
      when morphine was administered as a gel than a solution. The difference in pain
      experience between the two forms was not significant in the age group of 7-10
      years. CONCLUSION: The results indicate that most of the children tolerated
      rectal administration of morphine well in terms of pain experience, in both gel
      and solution form. The morphine gel, intended for rectal use appears to be the
      preparation of choice in children aged 1-6 years.

PMID- 16430414
TI  - The postoperative cardiovascular arrest of a 5-year-old male: an initial
      presentation of Duchenne's muscular dystrophy.
AB  - Anesthesia may be administered to patients with Duchenne's muscular dystrophy,
      but cases are reported in which apparently healthy children suffer hyperkalemic
      cardiac arrest. We present the case of a 5-year-old boy whose muscular dystrophy
      was discovered following a fatal, perioperative cardiac arrest in the
      postanesthesia care unit.

PMID- 16430415
TI  - Amitriptyline poisoning in a 2-year old.
AB  - We describe a case of a 2-year-old boy who ingested 35 mg.kg(-1) of
      amitriptyline. He developed central nervous system toxicity, as demonstrated by
      coma and seizures and cardiac toxicity (cardiac arrest) within 1 h of ingestion.
      The cardiac toxicity was refractory to standard therapy. His cardiac rhythm
      alternated between ventricular tachycardia and pulseless ventricular
      tachycardia/ventricular fibrillation for a period of 17 h. Following prolonged
      cardiopulmonary resuscitation and aggressive supportive management, the patient
      recovered both cardiovascularly and neurologically. An echocardiogram and MRI
      brain were subsequently performed and were normal. The patient was discharged 2
      weeks later with normal cognitive, behavioral and motor function. We discuss the
      benefit of prolonged and effective cardiopulmonary resuscitation in the
      management of this potentially fatal poisoning.

PMID- 16430416
TI  - Monitoring cerebral oxygenation in a pediatric patient undergoing surgery for
      vascular ring.
AB  - Regional cerebral oxygenation can be monitored using near-infrared spectroscopy
      (NIRS). Inadequacy of collateral cerebral circulation and regional cerebral
      ischemia during cardiac and vascular surgery may be detected by the use of NIRS
      monitoring. We report a 2-year-old child who underwent surgical repair of
      vascular ring and subclavian reimplantation, where use of NIRS helped in early
      detection and timely intervention to prevent prolonged cerebral ischemia.

PMID- 16430417
TI  - Onset and duration of mivacurium-induced neuromuscular blockade in children with
      Charcot-Marie-Tooth disease. A case series with five children.
AB  - BACKGROUND: The Charcot-Marie-Tooth (CMT) disorders are a group of hereditary
      motor and sensory neuropathies characterized clinically by peripheral muscle
      wasting and weakness. We hypothesized that unknown involvement of the muscle used
      for monitoring neuromuscular block may account for the conflicting reports about
      the effect of nondepolarizing neuromuscular agents in these patients. The aim of
      this study was to compare onset and recovery from mivacurium-induced
      neuromuscular block on the adductor pollicis and orbicularis oculi muscles.
      METHODS: We used mivacurium 0.2 mg.kg(-1) in five children (aged 7-12 years) with
      CMT type I undergoing propofol-fentanyl-oxygen-air anesthesia for orthopedic
      surgery. Using acceleromyography, neuromuscular transmission was monitored in
      parallel in the eye and thumb muscles, and onset and duration times were
      recorded. RESULTS: Following bolus administration of 0.2 mg.kg(-1) of mivacurium
      the onset time ranged between 135 and 240 s and 75 and 165 s in the eye and in
      the thumb, respectively. The recovery time varied between 5.3 and 16 min and 6
      and 31.3 min in the eye and in the thumb, respectively. CONCLUSIONS: In our small
      series of patients with CMT the clinical duration of mivacurium-induced
      neuromuscular block was similar to data known from children without neuromuscular
      disease.

PMID- 16430418
TI  - Anesthetic management in two siblings with glutaric aciduria type 1.
AB  - Glutaric aciduria type 1 (GA-1) is an inborn error of metabolism that results
      from a deficiency of glutaryl-CoA dehydrogenase. This disorder mainly manifests
      in early childhood and most patients with this condition develop a dystonic
      dyskinetic syndrome. We report the anesthetic management of two sisters with GA
      1, aged 30 and 17 months respectively at the time of surgery, who presented with
      macrocephaly and psychomotor delay. The children required CSF shunting procedures
      for hydrocephalus and subdural fluid collections, which were performed under
      total intravenous anesthesia with propofol and remifentanil.

PMID- 16430419
TI  - Hyponatremic seizures after suprapubic catheter placement in 7-year-old child.
AB  - We report a case of hyponatremic seizures in a 7-year old boy with spina bifida
      following cystoscopy and suprapubic catheter placement. Immediate postoperative
      cystogram and pelvic computed tomogram (CT) after the development of seizures
      demonstrated a fluid collection from the suprapubic catheter site into the
      anterior abdominal wall. The subsequent reabsorption of free water from the fluid
      collection, with the contribution of postoperative hypotonic intravenous fluid
      administration and possible transient inappropriate antidiuretic hormone (ADH)
      secretion resulted in acute dilutional hyponatremia and consequent seizures.
      Strategies to prevent hyponatremia in children during urological procedures, with
      emphasis on the importance of reserving free water as the irrigation fluid are
      discussed.

PMID- 16430420
TI  - Neurophysiological monitoring under anesthesia to position a child with extreme
      lumbar spine flexion for MRI and CT scan.
AB  - A novel application of neurophysiological monitoring enabled us safely to
      anesthetize and position a child with severe lumbosacral spine flexion for
      diagnostic MRI and CT scan. We conducted a propofol-based anesthetic to optimize
      somatosensory (SSEP) and transcranial electric motor (tceMEP) evoked potential
      amplitudes, thereby facilitating dynamic neurological monitoring while fully
      extending the patient supine. In cases outside the operating room involving
      extraordinary changes in patient position, anesthesia providers may consider
      utilizing neurophysiological monitoring.

PMID- 16430421
TI  - Thoracic epidural catheter in the management of a child with an anterior
      mediastinal mass: a case report and literature review.
AB  - We describe a case of an anterior mediastinal mass compressing the right main
      bronchus that required a biopsy through a thoracotomy incision. The anesthetic
      management of these patients is associated with several risks and challenges,
      including potential airway compression and cardiovascular collapse. Inhalation
      induction and maintenance of spontaneous respiration is recommended to preserve
      normal transpulmonary pressure gradient and improve flow through conducting
      airways. We placed a thoracic epidural catheter under general anesthesia as the
      main analgesic technique in order to maintain spontaneous breathing. The use of
      regional anesthesia, especially continuous epidurals in pediatric cardiothoracic
      anesthesia have many theoretical advantages including attenuation of the
      neuroendocrine response, facilitation of rapid extubation and improved
      ventilatory mechanics secondary to decreased narcotic requirements. The absolute
      risk of nerve injury and epidural hematoma for this procedure is unknown and hard
      to define in this patient population. We reviewed multiple studies and case
      reports addressing its safety and reported side effects. Finally, we emphasize
      that a thoracic epidural anesthesia is a reasonable choice that can be applied
      carefully in special situations even for children under general anesthesia.

PMID- 16430422
TI  - Increased blood loss during posterior spinal fusion for idiopathic scoliosis in
      an adolescent with Fontan physiology.
AB  - A 15-year-old patient with Fontan physiology experienced major blood loss during
      posterior spinal fusion for idiopathic scoliosis. Contributing factors for the
      increased blood loss and potentially useful measures to limit blood loss in
      patients with Fontan physiology are discussed.

PMID- 16430423
TI  - Caudal block complication in a patient with trisomy 13.
AB  - In this report we describe a complication of a caudal block in a 4-year-old child
      with trisomy 13. The patient's history was remarkable for microcephaly,
      developmental delay, seizures, apnea, and prolonged emergence times. Induction of
      anesthesia and tracheal intubation were uneventful. A caudal block was aborted
      after positive aspiration of cerebrospinal fluid. A radiogram suggestive of
      spinal dysraphism, found on subsequent review, was confirmed by a magnetic
      resonance imaging scan consistent with tethered cord and dural ectasia.
      Congenital abnormalities associated with trisomy 13 and cutaneous signs
      suggestive of spinal abnormalities are reviewed. Avoidance of neuraxial regional
      anesthesia in these patients is recommended.

PMID- 16430424
TI  - Anesthetic management of an infant with lupus and congenital complete heart
      block.

PMID- 16430425
TI  - Use of CobraPLA as a conduit for fiberoptic intubation in a child with neck
      instability.

PMID- 16430426
TI  - X-linked myotubular myopathy: anesthetic management for muscle biopsy.

PMID- 16430428
TI  - Anesthesia management of a child with adrenoleukodystrophy.

PMID- 16430427
TI  - Propofol anesthesia is an effective and safe strategy for pediatric endoscopy.

PMID- 16430429
TI  - An unusual position of central venous catheter.

PMID- 16430430
TI  - Clonidine as adjuvant for bupivacaine in ilioinguinal block does not prolong
      postoperative analgesia in pediatric and also in adult patients.

PMID- 16430432
TI  - Report on the 6th European Congress of Paediatric Anaesthesia of the Federation
      of European Associations of Paediatric Anaesthesia, September 1-3, 2005, in
      Cologne, Germany.

PMID- 16430433
TI  - Working better with GPs: lessons to be learned from a study of health care
      networks in the management of diabetes.

PMID- 16430434
TI  - Creutzfeldt-Jakob disease and vision.
AB  - This review describes a group of diseases known as the transmissible spongiform
      encephalopathies (TSEs), which affect animals and humans. Examination of affected
      brain tissue suggests that these diseases are caused by the acquisition and
      deposition of prion protein (PrP). Creutzfeldt-Jakob disease (CJD) is the most
      important form of TSE in humans with at least four different varieties of the
      disease. Variant CJD (vCJD), a new form of the disease found in the UK, has
      several features that differ from the classical forms including early age of
      onset, longer duration of disease, psychiatric presentation (for example,
      depression) and extensive florid plaque development in the brain. About 10 per
      cent of patients with CJD exhibit visual symptoms at disease presentation and
      approximately 50 per cent during the course of the disease. The most commonly
      reported visual symptoms include diplopia, supranuclear palsies, complex visual
      disturbances, homonymous visual field defects, hallucinations and cortical
      blindness. Saccadic and smooth pursuit movements appear to be more rarely
      affected. The agent causing vCJD accumulates in lymphoid tissue such as the
      spleen and tonsils. The cornea has lymphoid tissue in the form of corneal
      dendritic cells that are important in the regulation of the immune response in
      the anterior segment of the eye. The presence of these cells in the cornea has
      raised the possibility of transmission between patients via optical devices that
      contact the eye. Although such transmission is theoretically possible it remains
      highly improbable.

PMID- 16430435
TI  - Mobility performance of low-vision adults using an electronic mobility aid.
AB  - Visually impaired people rank obstacle location and identification as two of the
      most important mobility problems faced. Traditional mobility aids (the long cane)
      provide information about where an object is located but only within their
      limited (one metre) range. Although objects are located when traditional aids are
      used, it is unlikely that they are identified. The Bristol Mobility Aid (BMA) is
      an electronic travel aid that presents scene images to remaining residual vision
      in a number of view formats. Previous work has suggested visually impaired
      observers have better static object recognition using this aid. We investigated
      the mobility performance of subjects with retinitis pigmentosa using the BMA by
      determining the percentage preferred walking speed (PPWS), and the number of
      errors made with three different BMA headset views on an indoor mobility course.
      We found low-vision subjects had significantly reduced PPWS in two of the three
      headset views and interestingly, sighted subjects had significantly reduced PPWS
      when using the BMA in all three views. The numbers of errors made were
      significantly higher across all vision groups when the BMA was worn. We found
      that the BMA does not currently increase mobility in the visually impaired.
      Results are discussed in terms of modifications that could be made to the aid and
      methodological limitations.

PMID- 16430436
TI  - An evaluation of silicone-hydrogel lenses worn on a daily wear basis.
AB  - PURPOSE: To examine the clinical performance of two brands of silicone-hydrogel
      lenses when worn on a daily wear basis. METHODS: Fifty-six subjects with no
      ocular disease were enrolled at multiple sites in Australasia. Contact lenses
      made from galyfilcon A or lotrafilcon A were randomly assigned to each eye of the
      subject and the lenses were worn on a daily wear basis for a period of two weeks.
      Subjects did not know the identity of the lenses they wore. Clinical data and
      patient responses to a questionnaire were gathered at an initial visit and after
      two weeks of wear. RESULTS: For both lenses, the degree of limbal hyperaemia and
      bulbar conjunctival hyperaemia decreased significantly over the two-week wearing
      period. The eyes wearing galyfilcon A lenses showed an increase in conjunctival
      staining compared to the baseline measures. On average, galyfilcon A lenses
      decentred more and moved less than the lotrafilcon A lenses. The lotrafilcon A
      lenses showed a greater loss of wettability, as judged by practitioner grading,
      than the galyfilcon A lenses over the two-week period. The subjective responses
      showed strong preference for the galyfilcon A lens across 26 of 27 questions
      relating to comfort, vision, handling, preference and other subjective outcomes.
      DISCUSSION: The results show that different silicone-hydrogel lenses have
      different performance characteristics on the eye, when worn on a daily wear
      basis. Striving for high oxygen transmissibility at the expense of other
      properties may lead to a range of undesirable performance characteristics.

PMID- 16430437
TI  - Frosted cylindrical lens induced artefact on Humphrey automated perimetry.
AB  - BACKGROUND: The aim of this study was to assess the effect of a cylindrical
      corrective lens with frosted sides on Humphrey automated perimetry performed with
      a translucent spectacle occluder in the contralateral eye. METHODS: Ten healthy
      volunteers with cylindrical refractive errors of more than 1.50 DC had Humphrey
      visual fields (30-2) measured with the contralateral eye occluded with either a
      translucent spectacle occluder or an opaque patch. The order of testing with each
      occluder was randomised. Additionally, visual field examination with the opaque
      patch was performed on three volunteer subjects with deep-set eyes to establish
      the clinical significance of the frosted cylindrical lens induced artefact (CLA).
      The back vertex distances for the correcting lenses were measured for all tests.
      RESULTS: Eight out of 10 volunteers tested with the translucent occluder
      demonstrated CLA, which was absent when the opaque patch was used. The presence
      of an artefact corresponding to the axis of the cylinder was observed, when the
      vertex distance was more than 15 mm. Three subjects with deep-set eyes presented
      with CLA, even with the use of an opaque patch. DISCUSSION: Cylindrical lens
      artefacts can occur with increasing vertex distance when using a translucent
      spectacle occluder instead of an opaque patch. CLA is also seen in subjects with
      deep-set eyes.

PMID- 16430438
TI  - A clinical and optical evaluation of a modified lens for irregular corneae.
AB  - BACKGROUND: Correction of high regular and irregular astigmatism with rigid gas
      permeable contact lenses can result in discomfort, compromised corneal physiology
      and fluctuations in visual acuity due to excessive lens movement. Using a non
      probability sample, this study explored the optical, clinical and subjective
      performance of a modified countersunk piggyback lens (MCL) for the management of
      high regular and irregular corneal astigmatic refractive conditions, as the first
      phase for a larger randomised control study of the efficacy of the custom
      piggyback MCL system. METHOD: The sample was a single group of 10 patients (n =
      17 eyes) selected primarily on the basis of a history of failure with
      conventional management regimes. The objective clinical and optical performance
      of the MCL used in the management of high degrees of regular and irregular
      corneal astigmatic conditions was assessed, including measures of visual
      performance and ocular health. Subjective performance of the MCL was evaluated by
      patient feedback. RESULTS: Objective and subjective measures were analysed using
      appropriate statistical analyses. There was a significant improvement in the
      uncorrected vision and visual acuity (VA) with the MCL, as well as a significant
      improvement in refractive status. There was no statistically significant increase
      in adverse ocular responses with the MCL. Statistical analysis of the subjective
      responses indicated a strong acceptance of the MCL by all subjects, thus
      supporting the objective analysis indicating the superior performance of the MCL
      over prior conventional treatment regimens. DISCUSSION: The custom piggyback MCL
      performed successfully in the management of a range of high regular and irregular
      astigmatic conditions, which have been unsuccessfully managed with a range of
      conventional optical corrections. Despite the additional cost and handling
      implications of the two-lens system, the MCL was well accepted by all subjects
      due to its superior optical and clinical performance.

PMID- 16430439
TI  - Rapid onset and progression of posterior capsular opacification.
AB  - Posterior capsular opacification is a common complication following extracapsular
      cataract surgery. Its time of onset after surgery, rate of development and affect
      on vision vary greatly from one individual to another. In this case report, we
      describe the rapid development of posterior subcapsular opacification over a 12
      day period. This occurred four years after extracapsular cataract extraction and
      intraocular lens implantation via the technique of phako-emulsification.

PMID- 16430440
TI  - Human Thelaziasis occurrence in Taiwan.
AB  - A 62-year-old woman presented with unilateral eye swelling and itching.
      Subsequent examination showed the cause was an infestation of the parasitic worm
      Thelazia callipaeda. The vector leading to human infection is the fly. The
      possible mechanisms of infection for this patient are discussed. Although this is
      a known form of ocular infection, especially in Asia, this is one of few reported
      cases in Taiwan.

PMID- 16430452
TI  - Lymphocyte volume and conductivity indices of the haematology analyser Coulter
      GEN.S in lymphoproliferative disorders and viral diseases.
AB  - The haematology analyser Coulter GEN.S gives a set of data -'positional
      parameters'- defining white blood cell (WBC) populations by mean of index values
      (mean and standard deviation of volume, conductivity and scatter, used to
      identify the WBC populations). The volume and conductivity parameters related to
      the lymphocytes were analysed at diagnosis in patients suffering from chronic B
      lymphocytic leukaemia (B-CLL), other non-CLL lymphoproliferative disorders (OLPD)
      and viral diseases. The standard deviation of volume index (SDVI) is
      significantly higher in the three groups, whereas the mean volume index (MVI) is
      significantly lower in B-CLL, and increased in OLPD and viral diseases. These two
      groups could be distinguished by their mean conductivity index (MCI), which is
      significantly lower in viral disease group. Cut-offs were calculated for each
      parameter by the mean of Receiver Operating Characteristic (ROC) analysis. The
      study of the detection performances showed that the combination of lymphocyte
      count with SDVI, MVI and MCI could be used with a good sensitivity and
      specificity to discriminate between the most frequent lymphocyte pathologies,
      even in patients with normal lymphocyte count.

PMID- 16430453
TI  - Protein C and protein S levels can be accurately determined within 24 hours of
      diagnosis of acute venous thromboembolism.
AB  - In the 50% of cases of acute idiopathic venous thromboembolism, laboratory
      testing for inherited causes is often performed. Most physicians are under the
      impression that assays for protein C and protein S should not be measured at the
      time of diagnosis because of a high false positive rate. We performed a
      prospective cohort study from two outpatient thromboembolism clinics on
      consecutive patients with an objectively confirmed diagnosis of first acute
      idiopathic venous thromboembolism. Assays for protein C and protein S were
      performed prior to the initiation of oral anticoagulation therapy and within 24 h
      of diagnosis of venous thromboembolism. Abnormal results were repeated when
      patients discontinued oral anticoagulant therapy. Of 253 patients tested for both
      protein C and protein S, 229 (91%; 95% confidence interval 87-94%) were negative
      and 484 of 508 (95%) tests were normal. Of the 24 initial abnormal results, 21
      were repeated and 10 (48%; 95% confidence interval 26-70%) were still abnormal.
      Overall, 97.8% of initial protein C and protein S results were accurate. If
      protein C and protein S are measured at the time of diagnosis of acute venous
      thromboembolism, the majority of the results will be normal and false positives
      are uncommon.

PMID- 16430454
TI  - Effect of sex difference on platelet aggregation using an optical method in
      healthy subjects.
AB  - There are many studies reporting conflicting results of sex differences on
      various platelet functions. The purpose of this study was to investigate whether
      sex differences could affect platelet aggregation results using an optical method
      in healthy subjects. A total of 42 subjects, 21 males and 21 females, were
      included in the study. Platelet aggregation was induced by adenosine diphosphate
      (ADP; 5 microm), collagen (2 microg/ml), and epinephrine (10 microm). Optical
      aggregation was performed using a turbidometric method. In all platelet
      aggregation tests ADP, collagen and epinephrine were studied; there was no
      significant difference between females and males in platelet aggregation
      amplitudes and slopes. As a result, sex difference does not affect platelet
      aggregation performed with this optical method in healthy subjects. This result
      supports that there is no need for sex differentiation while composing control
      groups in platelet aggregation studies using the optical method.

PMID- 16430455
TI  - The value of genetic testing for type 2B Von Willebrand disease.
AB  - Von Willebrand disease (VWD) is an inherited bleeding disorder that may be
      associated with significant morbidity, but is often a diagnostic challenge. While
      an appropriate clinical bleeding history suggests the condition, current
      laboratory screening investigations lack the sensitivity and specificity to
      confirm the diagnosis in many cases. Recently, much work has gone into
      characterizing the genetic mutations associated with the various subtypes of VWD.
      We report a case in which the diagnosis of VWD type 2B was made via genetic
      testing, illustrating its value as a useful diagnostic tool.

PMID- 16430456
TI  - Detection of malignant haematopoietic cells in the cerebrospinal fluid by
      conventional cytology and flow cytometry.
AB  - Morphological evaluation of cerebrospinal fluid (CSF) samples by light microscopy
      is the method of choice for the detection of central nervous system involvement
      in patients with haematological malignancies. In this retrospective study, we
      assessed the value of three-colour immunophenotyping by flow cytometry in
      addition to conventional cytology in 28 patients with and 17 patients without pre
      existent haematological malignancy in whom CSF analysis was performed because of
      neurological abnormalities (n = 37) or as part of routine staging procedures (n =
      8). Four samples could not be analysed by flow cytometry because of insufficient
      cell numbers. CSF involvement was detected in a total of 18 patients, in 12 by
      both cytology and flow cytometry, and in three each by either cytology or flow
      cytometry alone. Discordant results were particularly frequent in patients with
      low CSF cell numbers and B cell neoplasms. When combined with conventional
      cytology, flow cytometric analysis improves the detection rate of CSF involvement
      in patients with haematological malignancies. It is particularly useful in B cell
      neoplasms with low CSF cell numbers.

PMID- 16430457
TI  - Prognostic importance of soluble CD23 in B-cell chronic lymphocytic leukemia.
AB  - Soluble CD23 (sCD23) was proposed as a marker of disease activity and as an
      important prognostic parameter in B-cell chronic lymphocytic leukemia (B-CLL). In
      this study, prognostic significance of sCD23 in B-CLL was examined according to
      its temporal relationship with the known clinical parameters of the disease, CD38
      and ZAP-70. Serum sCD23 levels of 36 B-CLL patients, followed up in our clinic
      between 1999 and 2005, and 15 healthy subjects were measured with enzyme-linked
      immunosorbent assay. The mean serum sCD23 level of the B-CLL patients (210.72 +/-
      193.67 and 6-600 U/ml) was significantly higher than the control group (18.20 +/-
      14.30 and 6-50 U/ml). Seventy-eight percent of the B-CLL patients with lymphocyte
      doubling time (LDT) <12 months and 24% of patients with LDT >12 months had high
      sCD23 levels (P = 0.008). Meanwhile, 81% of the patients with diffuse bone marrow
      infiltration and 33% of patients with nondiffuse infiltration had high levels of
      serum sCD23 (P = 0.029). A significant difference was found between B-CLL
      patients with Binet stages A and C (P = 0.009). Peripheral blood flow cytometry
      of the patients revealed a significant CD38 expression in patients with high
      serum sCD23 levels (P = 0.002). Similarly, an increased bone marrow zeta-chain
      associated protein kinase-70 (ZAP-70) expression was seen in patients with high
      serum sCD23 levels (P = 0.009, correlation co-efficient was 0.714). Cumulative
      and the progression free survivals of the patients with low serum sCD23 levels
      were 60.1 +/- 5.7 months [95% confidence interval (CI); 49.0-71.2] and 51.1 +/-
      6.6 months (95% CI; 38.0-64.1), respectively. However, they were 43.8 +/- 6.5
      months (95% CI; 31.0-56.6) and 26.5 +/- 6.4 months (95% CI; 14.0-39.1) in
      patients with high levels. Serum sCD23 is increased in B-CLL patients and can be
      used in the clinical follow-up of the disease in prediction of the tumor mass and
      prognosis.

PMID- 16430458
TI  - sVE-cadherin and sCD146 serum levels in patients with multiple myeloma.
AB  - The role of angiogenesis in multiple myeloma (MM) pathogenesis is well
      established. Angiogenesis is linked to the functional state of endothelial
      junctions that are modulated by the growth and activation of endothelial cells.
      CD146 and vascular endothelial-cadherin (VE-cadherin) are cell adhesion molecules
      localized at the endothelial junction. The aim of the study was to assess sVE
      cadherin and sCD146 serum levels in MM patients. Forty-six untreated patients
      with MM were included in this study. In addition, 23 of 46 patients were analyzed
      again in partial remission after initial chemotherapy. Twenty-two samples from
      healthy volunteers were evaluated as the control. There was no significant
      difference in sCD146 level between MM patients and the control (511 +/- 177.2 vs.
      460.9 +/- 156.9 ng/ml respectively). In untreated MM patients, sVE-cadherin level
      was significantly higher than in the control (1.36 +/- 0.55 vs. 0.63 +/- 0.56
      ng/ml respectively; P < 0.05). In untreated MM patients, sVE-cadherin level was
      significantly higher than in MM patients in partial remission (1.36 +/- 0.55 vs.
      0.5 +/- 0.33 respectively; P < 0.05). sVE-cadherin but not sCD146 serum level was
      increased in untreated MM patients and decreases after chemotherapy in patients
      in partial remission. VE-cadherin may reflect intensity of angiogenesis in MM and
      may be useful in prognosis of response to treatment.

PMID- 16430459
TI  - Quantitative analysis of chimerism using a short tandem repeat method on a
      fluorescent automated DNA sequencer.
AB  - Stem cell transplantation (SCT) is the treatment of choice for a number of
      malignant and nonmalignant diseases. Monitoring of SC engraftment or
      microchimerism (MC) is important for diagnosis of relapse, rejection or graft vs.
      host disease (GVHD). The goal of this study was to develop a sensitive and
      relatively simple method for MC lineage analysis using the Visible Genetics
      fluorescence automated sequencer. Sensitivity of the method was studied by
      polymerase chain reaction (PCR) amplification of informative short tandem repeats
      (STR) using donor/recipient DNA mixtures as the templates and DNA extracted from
      donor and recipient CD3+, CD19+ and CD15+ cells mixed at various ratios. Semi
      quantitative analysis was performed using the Visible Genetics software and
      percent of donor specific signal was calculated. The sensitivity of this method
      varied from 0.8% to 6.2% for both DNA and cellular MC in CD3+, CD19+ and CD15+
      subsets. Regression analysis revealed linearity (r = 0.94) between the number of
      donor cells in the mixture and intensity of MC fluorescent signal. These data
      indicate that the Visible Genetics polyacrylamide gel sequencer can be
      successfully used for MC analysis in SC recipients providing a relatively high
      level of sensitivity.

PMID- 16430460
TI  - Current hematological findings in cobalamin deficiency. A study of 201
      consecutive patients with documented cobalamin deficiency.
AB  - With the introduction of automated assays for measuring serum cobalamin levels
      over the last decades, the hematological manifestations related to cobalamin
      deficiency have been changed from the description reported in 'old' studies or
      textbooks. We studied the hematological manifestations or abnormalities in 201
      patients (median age: 67 +/- 6 years) with well-documented cobalamin deficiency
      (mean serum vitamin B12 levels 125 +/- 47 pg/ml) extracted from an observational
      cohort study (1995-2003). Assessment included clinical features, blood count and
      morphological review. Hematological abnormalities were reported in at least two
      third of the patients: anemia (37%), leukopenia (13.9%), thrombopenia (9.9%),
      macrocytosis (54%) and hypegmented neutrophils (32%). The mean hemoglobin level
      was 10.3 +/- 0.4 g/dl and the mean erythrocyte cell volume 98.9 +/- 25.6 fl.
      Approximately 10% of the patients have life-threatening hematological
      manifestations with documented symptomatic pancytopenia (5%), 'pseudo' thrombotic
      microangiopathy (Moschkowitz; 2.5%), severe anemia (defined as Hb levels <6 g/dl;
      2.5%) and hemolytic anemia (1.5%). Correction of the hematological abnormalities
      was achieved in at least two-thirds of the patients, equally well in patients
      treated with either intramuscular or oral crystalline cyanocobalamin. This study,
      based on real data from a single institution with a large number of consecutive
      patients with well-documented cobalamin deficiency, confirms several 'older'
      findings that were previously reported before the 1990s in several studies and in
      textbooks.

PMID- 16430461
TI  - Treatment of refractory fludarabine induced autoimmune haemolytic with the anti
      CD20 monoclonal antibody rituximab.
AB  - A patient with cold-type autoimmune haemolytic anaemia for 8 years developed
      progressive B cell chronic lymphocytic leukaemia (CLL). Despite the risk of
      fludarabine induced exacerbation of haemolysis, he was given aggressive anti-CLL
      therapy with six courses of FCR (fludarabine 25 mg/m2 D1-3, cyclophosphamide 250
      mg/m2 D2-4 and rituximab 375 mg/m2 D1) every 4 weeks. This resulted in a marked
      acute increase in haemolysis shortly after completing each course of fludarabine.
      However, haemolysis had settled to its baseline level by the time of subsequent
      courses of FCR. FCR resulted in complete clinical remission of CLL but residual
      haemolysis persisted. The patient was then given four weekly infusions of single
      agent rituximab, resulting in ongoing remission of haemolysis. In this patient,
      rituximab appears to have controlled fludarabine induced exacerbation of
      autoimmune haemolysis. In addition, subsequent single agent rituximab therapy
      resulted in prolonged remission of cold-type autoimmune haemolytic anaemia. It
      remains to be seen if the addition of rituximab will allow other patients with a
      positive direct Coomb's test and/or autoimmune haemolysis to receive fludarabine
      containing chemotherapy without undue risk of life-threatening haemolytic
      anaemia.

PMID- 16430462
TI  - Sickle cell 'girdle syndrome' progressing to ischaemic colitis and colonic
      perforation.
AB  - Abdominal pain of presumed vasocclusive origin, often termed 'girdle syndrome'
      because of the circumferential distribution of the pain, is common in sickle cell
      anaemia (SCA). Evidence of progression to bowel infarction is rare. A 27-year-old
      man with SCA developed chest and abdominal pain unresponsive to opiate analgesia.
      Abdominal X-ray showed dilated bowel loops because of partial obstruction.
      Despite reduction of HbS to 23% by automated red cell exchange, abdominal pain
      worsened. A CT scan was the most informative investigation and showed free
      peritoneal air. He underwent emergency hemicolectomy and reversible ileostomy
      formation. Histology of the resected colon was consistent with acute ischaemic
      colitis. Early surgical intervention remains essential in SCA when abdominal pain
      does not respond to maximal therapy including red cell exchange: as this case
      illustrates, sickle girdle syndrome has the capacity to progress to irreversible
      ischaemic colitis and necrotic perforation of the bowel wall.

PMID- 16430463
TI  - 'Double hit' from streptococcal pneumonia and hypersensitivity pneumonitis
      associated with anagrelide.
AB  - We report a case of unresolved streptococcal pneumonia in a patient taking
      anagrelide for essential thrombocythaemia. Resolution only occurred after
      discontinuing anagrelide and the institution of corticosteroid therapy, which
      resulted in dramatic improvement. There has been only one previous case report of
      anagrelide causing hypersensitivity pneumonia. We postulate this patient suffered
      a 'double hit' from streptococcal infection and anagrelide.

PMID- 16430464
TI  - Severe folate deficiency in pregnancy with normal red cell folate level.
AB  - We report here a case of megaloblastic anaemia in late pregnancy, which leads us
      to question whether folate supplements should be recommended in the UK routinely
      throughout pregnancy and not just in the preconception period and first
      trimester.

PMID- 16430465
TI  - Enteroviral meningoencephalitis in a patient with non-Hodgkin's lymphoma treated
      previously with rituximab.
AB  - A 75-year-old man, with a long history of recurrent lymphoplasmacytoid lymphoma,
      presented with diffuse large-cell lymphoma affecting adrenal glands and causing
      severe hypoadrenalism. The lymphoma responded to rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy. Seven months
      postcompletion of chemotherapy, he developed signs of gastroenteritis and
      septicaemia. He deteriorated 24 h postadmission with a significant fall in
      Glasgow Coma Scale Score. Polymerase chain reaction testing of cerebrospinal
      fluid suggested enteroviral encephalitis. He responded symptomatically to
      intravenous immunoglobulins. His immunoglobulin levels were monitored weekly and
      supplemented to maintain immunoglobulin G level at 10 g/l, but in spite of this,
      his neurological condition deteriorated and he died after 14 weeks. Rituximab can
      cause prolonged B-cell deficiency. We speculate that profound immunosuppression
      induced by rituximab, together with previous chemotherapy, predisposed this
      patient to fatal enteroviral meningoencephalitis.

PMID- 16430468
TI  - Sensitivity and specificity of immunohistochemical markers used in the diagnosis
      of epithelioid mesothelioma: a detailed systematic analysis using published data.
AB  - AIMS: Immunohistochemistry is frequently employed to aid the distinction between
      mesothelioma and pulmonary adenocarcinoma metastatic to the pleura, but there is
      uncertainty as to which antibodies are most useful. We analysed published data in
      order to establish sensitivity and specificity of antibodies used to distinguish
      between these tumours with a view to defining the most appropriate
      immunohistochemical panel to use when faced with this diagnostic problem. METHODS
      AND RESULTS: A systematic analysis of the results of 88 published papers
      comparing immunohistochemical staining of a panel of antibodies in mesothelioma
      with epithelioid areas, and pulmonary adenocarcinoma metastatic to the pleura.
      Results for a total of 15 antibodies were analysed and expressed in terms of
      sensitivity and specificity. The most sensitive antibodies for identifying
      pulmonary adenocarcinoma were MOC-31 and BG8 (both 93%), whilst the most specific
      were monoclonal CEA (97%) and TTF-1 (100%). The most sensitive antibodies to
      identify epithelioid mesothelioma were CK5/6 (83%) and HBME-1 (85%). The most
      specific antibodies were CK5/6 (85%) and WT1 (96%). CONCLUSIONS: No single
      antibody is able to differentiate reliably between these two tumours. The use of
      a small panel of antibodies with a high combined sensitivity and specificity is
      recommended.

PMID- 16430469
TI  - Immunoglobulin and T-cell receptor gene rearrangement in Castleman's disease:
      molecular genetic analysis.
AB  - AIMS: Castleman's disease (CD) is a rare heterogeneous disorder that is
      associated with an increased risk of developing lymphoma. Whether CD is primarily
      hyperplastic or neoplastic in origin is not yet clear. The aim of this study was
      to investigate CD further by determining the clonality status of its lymphocyte
      populations. METHODS AND RESULTS: We reviewed 20 patients with CD, 15 with the
      hyaline-vascular type and five with the plasma cell type. Immunoglobulin (JH) and
      T-cell receptor (TCR) gene rearrangements were examined using polymerase chain
      reaction and Southern blotting techniques. B-lymphocyte clonality was also
      assessed by flow cytometry (FC) and by immunohistochemistry (IHC). The age range
      of the patients was 15-66 years: nine female and 11 male. Monoclonal
      rearrangement of the immunoglobulin (JH) gene was detected in only one case. No
      cases were positive for monoclonal rearrangement of the TCR gene. All of the
      cases except one were negative for immunoglobulin light chain restriction by both
      FC and IHC. CONCLUSIONS: The lymphoid cells in CD are most commonly polyclonal in
      origin, which supports a non-neoplastic origin. However, rare cases may show
      lymphocyte monoclonality, which could represent the development of a neoplastic
      population. The latter cases should be followed closely.

PMID- 16430470
TI  - Loss of CD19 expression in B-cell neoplasms.
AB  - AIMS: To investigate whether an antibody against an intracellular epitope can
      detect CD19 in routine biopsy specimens and thus to document in detail its
      expression in human lymphomas. METHOD AND RESULTS: A polyclonal antibody to the C
      terminus of CD19 was used to immunostain paraffin-embedded samples of normal and
      neoplastic lymphoid tissues. CD19 was widely expressed in normal B cells and in
      extramedullary plasma cells. It was found in most B-cell neoplasms, but
      expression in follicular lymphoma was weak (33/69) or negative (four cases).
      Similarly, CD19 expression in diffuse large B-cell lymphomas was weak (28/56) or
      negative (eight cases). In T-cell-rich B-cell lymphomas, CD19 was also weak
      (4/10) or negative (three cases). CD19 was often absent in post-transplant B
      lymphoproliferative disease, classical Hodgkin's disease and plasma cell
      neoplasms. An unexpected finding was the frequent absence of CD19 in the
      neoplastic cells in lymphocyte predominant Hodgkin's disease. CONCLUSIONS: CD19
      can now be detected in routine biopsy specimens. In contrast to the classical pan
      B marker CD20, CD19 is not always strongly expressed in B-cell neoplasms.
      Furthermore, the lymphocytic and histiocytic (L&H) cells of lymphocyte
      predominant Hodgkin's disease (which express most B-cell-associated markers)
      commonly lack CD19.

PMID- 16430471
TI  - Evaluation of neoplastic human mast cells by tryptase-immunoelectron microscopy.
AB  - AIMS: To analyse and characterize the ultrastructural morphology of normal tissue
      mast cells (MC) and neoplastic bone marrow MC. METHODS: We have examined the
      ultrastructure and cytomorphological features of MC derived from cord blood
      cells, neoplastic bone marrow MC in patients with systemic mastocytosis (SM, n =
      4), myelomastocytic leukaemia (MML, n = 2), mast cell leukaemia (MCL, n = 2) and
      tryptase-positive acute myeloid leukaemia (AML, n = 4). RESULTS: Based on their
      ultrastructure and morphology, four distinct cell types could be delineated: (i)
      mature well-granulated tissue MC exhibiting a round central nucleus; (ii)
      atypical MC type I with oval nuclei, hypogranulated cytoplasm, and prominent
      surface projections; (iii) immature atypical MC with bi- or polylobed nuclei
      (atypical MC type II = promastocytes); and (iv) metachromatic blasts. Type I
      atypical MC were detected in a patient with indolent SM, whereas type II MC and
      metachromatic blasts were primarily found in MML, MCL and tryptase-positive AML.
      In all samples examined, the identity of MC could be reconfirmed by
      immunoelectron microscopy, irrespective of the stage of cell maturation or the
      disease variant, all types of MC contained tryptase in their cytoplasmic
      granules. CONCLUSION: Immunoelectron microscopy may be a helpful approach in
      confirming the identity of neoplastic MC in myeloid neoplasms.

PMID- 16430472
TI  - Comparison of immunohistochemistry by automated cellular imaging system (ACIS)
      versus fluorescence in-situ hybridization in the evaluation of HER-2/neu
      expression in primary breast carcinoma.
AB  - AIMS: Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH)
      are both commonly used assays for evaluation of HER-2/neu status in breast
      cancer. However, there is still no consensus on which method is most predictive
      of patient response to Herceptin. Recently, the automated cellular imaging system
      (ACIS) has been shown to improve the accuracy and reproducibility in scoring IHC.
      Our aim was to compare the results of HER-2/neu expression and gene amplification
      in the same patients by IHC using the ACIS system and by FISH. METHODS AND
      RESULTS: Two hundred and forty-seven breast cancer cases were studied. The
      concordance rate between IHC-ACIS (> or = 2.2) and FISH (> or = 2.0) was 94%.
      Fifteen patients were discordant; three had borderline FISH values and three had
      borderline IHC values. The other nine discordant cases consisted of five IHC
      ACIS+, FISH- and six IHC-ACIS-, FISH+. HER-2/neu overexpression was more common
      in tumours that were high-grade, aneuploid, progesterone receptor and bcl-2
      negative, with MIB-1 > 10%. CONCLUSION: HER-2/neu assessment by the ACIS is
      reliable, rapid and inexpensive, and correlates highly with results obtained by
      FISH.

PMID- 16430473
TI  - p53 immunostaining in lichen sclerosus is related to ischaemic stress and is not
      a marker of differentiated vulvar intraepithelial neoplasia (d-VIN).
AB  - AIM: To analyse p53 immunoreactivity in 207 biopsy specimens of lichen sclerosus
      (LS) and "differentiated vulvar intraepithelial neoplasia" (d-VIN), a postulated
      precursor lesion for LS-associated vulvar squamous cell carcinoma (SCC), which is
      characterized by atypical basal keratinocyte proliferations with p53+
      basal/suprabasal keratinocyte nuclei. METHODS AND RESULTS: Forty early, 78
      classic, 30 hypertrophic vulvar LS, 26 paediatric vulvar and penile LS, 33 vulvar
      LS-associated SCC and 30 vulvar/penile control specimens were examined for p53
      expression and the presence of d-VIN. Nuclear p53 staining was observed in
      175/207 LS biopsy specimens. Eighty percent of early and 69% of paediatric LS
      showed discontinuous/continuous p53 staining in basal keratinocytes. Classic LS
      showed no p53 staining in 17%, discontinuous basal keratinocyte staining in 20%,
      continuous basal keratinocyte staining in 58%, basal/suprabasal staining in 5%.
      Hypertrophic LS revealed basal keratinocyte staining in 32% and basal/suprabasal
      staining in 61%. p53 staining was associated with sclerosis of blood vessels and
      dermis, lymphoid infiltrates, vasculitis and hypertrophic LS. d-VIN was seen in
      2% of LS alone and in 24% of LS-associated SCC. CONCLUSION: d-VIN in LS is rare,
      while p53 staining is common and best explained as an ischaemic stress response
      due to poor oxygenation, vasculitis and inflammation rather than as a marker of a
      precancerous lesion in LS.

PMID- 16430475
TI  - Expression of matrix metalloproteinases in benign and malignant follicular
      thyroid lesions.
AB  - AIMS: To examine expression of matrix metalloproteinases (MMPs) and related
      proteins in follicular thyroid lesions (FTLs) and to determine their usefulness
      for differential diagnosis of FTLs, particularly between minimally invasive
      carcinoma and adenoma. METHODS AND RESULTS: Six widely invasive follicular
      carcinomas (WIFCs), 15 minimally invasive follicular carcinomas (MIFCs), 19
      follicular adenomas (FAs) and 10 adenomatous goitres (AGs) were analysed
      immunohistochemically for MMP-1, MMP-2, MMP-7, MMP-9, membrane-type 1-MMP (MT1
      MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). MMP-1 was
      positive in all FTLs. MMP-2 and MMP-7 were positive in more than 80% of WIFC and
      MIFC cases, whereas they were negative in all FA and AG cases except one MMP-2+
      FA (P < 0.001). MMP-9 stained positive significantly more in MIFC than FA or AG
      cases (P < 0.05, respectively). The positivity of MT1-MMP and TIMP-2 was
      different among some of the FTLs, but with no significant difference between MIFC
      and FA cases. In-situ hybridization of MMP-2 and MMP-7 mRNA in selected cases
      demonstrated the expression of these enzymes in the tumour cells as well as in
      some stromal cells. CONCLUSIONS: Our results confirm MMP expression mainly in
      malignant FTLs and suggest that MMP-2 and MMP-7 may be useful markers to
      distinguish MIFC from FA.

PMID- 16430474
TI  - Cell cycle regulators and apoptosis-associated proteins in relation to
      proliferative activity and degree of apoptosis in HNPCC versus sporadic
      endometrial carcinoma.
AB  - AIMS: Mismatch repair gene malfunction occurs early in the carcinogenesis of
      hereditary non-polyposis colorectal cancers (HNPCCs), leading to an accelerated
      accumulation of mutations and possibly to change in expression of cell cycle
      proteins. There is strong evidence that tumorigenesis in HNPCCs differs from
      sporadic ones. HNPCC-related endometrial cancers are less well studied. Our aim
      was to compare expression of cell cycle and apoptosis-related proteins in
      relation to proliferation and apoptosis in HNPCC-related and sporadic endometrial
      cancers to identify differences in their carcinogenetic pathways. METHODS AND
      RESULTS: Eighteen HNPCC-related endometrial cancers, each matched by tumour type,
      stage and grade with two sporadic endometrial cancers, were examined for
      proliferation, apoptosis and the expression of oestrogen and progesterone
      receptors, cyclin B1, D3 and E, p21, p27, bcl-2, bax, p53 and COX-2. No
      differences in proliferation or apoptotic indices were detected between HNPCC
      related and sporadic endometrial cancers. Cyclin B1 expression was significantly
      higher in HNPCC-related cancers than in sporadic endometrial cancers. More HNPCC
      related endometrial cancers had total loss of bax expression. CONCLUSIONS: Apart
      from differences in cyclin B1 and bax expression, HNPCC-related and sporadic
      endometrial cancers are comparable. The subtle differences detected are
      consistent with the minor clinical diversity between HNPCC-related and sporadic
      endometrial cancers.

PMID- 16430477
TI  - Benign metastasizing mesothelial cells in an axillary lymph node secondary to a
      chest wall fibromatosis.

PMID- 16430476
TI  - The role of histopathology in establishing the diagnosis of tuberculous
      pericardial effusions in the presence of HIV.
AB  - AIMS: To establish the influence of human immunodeficiency virus (HIV) infection
      on the histopathological features of patients presenting with tuberculous
      pericarditis. METHODS AND RESULTS: A prospective study was carried out at
      Tygerberg Academic Hospital, South Africa; 36 patients with large pericardial
      effusions had open pericardial biopsies under general anaesthesia and were
      included in the study. Patients underwent pericardiocentesis, followed by daily
      intermittent catheter drainage; a comprehensive diagnostic work-up (including
      histopathology of the pericardial tissue) was also performed. Histological
      tuberculous pericarditis was diagnosed according to predetermined criteria.
      Tuberculous pericarditis was identified in 25 patients, five of whom were HIV+.
      The presence of granulomatous inflammation (with or without necrosis) and/or
      Ziehl-Neelsen positivity yielded the best test results (sensitivity 64%,
      specificity 100% and diagnostic efficiency 75%). CONCLUSIONS: Co-infection with
      HIV impacts on the histopathological features of pericardial tuberculosis and
      leads to a decrease in the sensitivity of the test. In areas which have a high
      prevalence of tuberculosis, the combination of a sensitive test such as adenosine
      deaminase, chest X-ray and clinical features has a higher diagnostic efficiency
      than pericardial biopsy in diagnosing tuberculous pericarditis.

PMID- 16430478
TI  - Intestinal histoplasmosis mimicking Whipple's disease.

PMID- 16430479
TI  - Acinar cell carcinoma of the pancreas in a young patient with cells
      immunoreactive for somatostatin.

PMID- 16430480
TI  - Multiple mixed adenoma-focal nodular hyperplasia of the liver associated with
      spontaneous intrahepatic porto-systemic shunt: a new type of vascular
      malformation associated with the multiple focal nodular hyperplasia syndrome?

PMID- 16430482
TI  - Clinicopathological and immunohistochemical studies of thymic-related tumours in
      thyroid gland: report of five cases.

PMID- 16430483
TI  - Proliferative intraductal lesion arising in ectopic breast tissue within axillary
      lymph node.

PMID- 16430481
TI  - A meningiomatous perineurial tumour located in the mesentery. An ultrastructural
      and immunohistochemical study.

PMID- 16430484
TI  - Interfollicular Hodgkin's lymphoma and Castleman's disease.

PMID- 16430485
TI  - The expression of immunologically relevant surface molecules in the human
      tracheal mucosa is unaffected post mortem.

PMID- 16430486
TI  - Primary synovial sarcoma of the prostate.

PMID- 16430489
TI  - Coat condition, housing condition and measurement of faecal cortisol metabolites-
      a non-invasive study about alopecia in captive rhesus macaques (Macaca mulatta).
AB  - BACKGROUND: Previous studies have characterized alopecia in captive rhesus
      macaques (Macaca mulatta) by a mixed partial to complete alopecia in a bilateral
      symmetric pattern. METHODS: In this study, coat condition assessments were
      related to exogenous and endogenous factors in captive rhesus macaques under
      different housing conditions in order to identify disturbances in environmental
      factors controlling or influencing hair growth. Additionally, the degree of
      alopecia was investigated in relation to adrenal endocrine function as an
      indicator of social stress using faecal glucocorticoid measurements. RESULTS:
      Hair loss was found to vary with season and sex, was most pronounced in adult
      females during the winter and spring months. Generally, infants were not
      affected, but alopecia developed during adolescence. However, the housing system,
      available enclosure space and variations in group size and composition also
      appeared to influence coat condition. Levels of immunoreactive cortisol
      metabolites (11-oxoetiocholanolone) in faeces were significantly negatively
      correlated with alopecia, suggesting a relationship between hypothalamic
      pituitary-adrenal (HPA) axis activity and hair loss in captive rhesus macaques.
      CONCLUSIONS: Although the present study demonstrates the influence of the HPA
      axis on coat condition, it is not known if hair loss is caused by abnormal
      behaviour or hormonal imbalances of the HPA axis itself. Our data suggest that
      alopecia in rhesus macaques is a highly complex multicausal disorder.

PMID- 16430490
TI  - Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is an invaluable tumor marker for the
      detection of early prostate cancer, and can be a target for active immunotherapy
      of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey
      (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific
      therapies. METHODS: RNA was isolated from the prostate of cynomolgus monkeys, and
      PSA gene products were amplified by reverse transcriptase-polymerase chain
      reaction using primers from conserved regions of human and rhesus monkey (Macaca
      mulatta) PSA genes. These amplified products were then sequenced. RESULTS: The
      cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and
      99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus
      PSA genes, an open-reading frame of 261 amino acids was identified for the
      cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted
      to the prostate, as it is in humans. CONCLUSIONS: The high identity between human
      and cynomolgus PSA sequences suggests that the cynomolgus monkey should be
      studied further for its potential as a large animal model to evaluate PSA
      specific therapies.

PMID- 16430491
TI  - The ductus venosus and intrahepatic venous system in Callithrix jacchus jacchus
      and Macaca fascicularis fetuses.
AB  - BACKGROUND: The ductus venosus (DV) and the intrahepatic branches of the portal
      vein are arranged as parallel vessels. Blood shunting through the DV ensures
      fetal survival during periods of stress. The availability of a suitable animal
      model with similar structure and function to the human fetus would greatly
      improve the understanding of DV function. The anatomical and histological
      structure of the DV has not been thoroughly investigated in non-human primate
      species. METHODS: Morphological investigations were performed on eight marmoset
      (Callithrix jacchus jacchus) at 112.5 +/- 5.5 days gestational age (mean +/- SEM)
      and four near-term (165 days) cynomolgus (Macaca fascicularis) fetuses. RESULTS:
      The DV drains into the collectus venosus. An asymmetrical muscular lip forms a
      contractile element of the isthmic portion of the DV. A spherical 'dividing'
      eminence was found on the dorsal wall of the venous collector just above the
      outlet of the DV in marmoset fetuses. CONCLUSIONS: Our findings regarding the
      structure of the DV in cynomolgus and marmoset fetuses were generally in
      agreement with previous descriptions of the morpho-histological structure of the
      DV in human fetuses.

PMID- 16430492
TI  - Normative nerve conductions in the tail of rhesus macaques (Macaca mulatta).
AB  - BACKGROUND: The aim of this study was to test the feasibility of using the tail
      of Macaca mulatta for neurophysiological testing of the peripheral nervous
      system. METHODS: Motor and sensory nerve conduction studies (NCS) of the tail
      were obtained by surface stimulation and recording. The technique utilized was
      novel. Unlike other NCS obtained from other peripheral nerves, this technique did
      not require any special neurophysiological expertise. RESULTS: The latency of the
      motor and sensory response was 2.5 +/- 0.71 and 1.1 +/- 0.27 ms respectively. The
      amplitude of the motor and sensory response was 8.1 +/- 5.1 mV and 14.6 +/- 9.4
      microV respectively. Similar to human beings, there was a statistically
      significant relationship between age and motor amplitude, motor latency and
      sensory latency. CONCLUSIONS: Based on our results, a relatively simple,
      reproducible neurophysiological monitoring technique of the peripheral nervous
      system is possible.

PMID- 16430493
TI  - Characterization of obesity in Japanese monkeys (Macaca fuscata) in a pedigreed
      colony.
AB  - BACKGROUND: Japanese monkey, Macaca fuscata, is recognized as the monkey species
      inhabiting the northernmost area in the world, and thus likely to possess unique
      fat-depositing mechanisms to resist cold weather in winter. We report that obese
      females are present in the Wakasa group of Japanese monkey reared in an open
      enclosure of the Primate Research Institute, Kyoto University. METHODS AND
      RESULTS: Eight of 12 females were categorized as obese, showing percentage body
      fat of over 22%. The levels of serum leptin (mean +/- SD, 4.9 +/- 2.3 ng/ml)
      measured in these obese monkeys were significantly higher than those of non-obese
      peers of the same group (n = 4; 1.2 +/- 0.5 ng/ml) and another Japanese monkey
      group (Takahama, n = 14; 0.8 +/- 0.25 ng/ml); however, serum levels of
      adiponectin, insulin, glucose, hemoglobin A1c, and fructosamine did not differ
      between obese and non-obese monkeys. Few serum lipid parameters such as
      triglyceride and cholesterol showed lower levels in obese monkeys than their non
      obese peers. CONCLUSIONS: These results show that these obese monkeys in the
      Wakasa group have not developed obesity-related diseases/disorders such as
      diabetes. In the Wakasa group, the frequency of obese individuals was high in
      some maternal lineages, suggesting that genetic factors responsible for obesity
      may have been inherited in these lineages.

PMID- 16430494
TI  - Fetal ultrasonography: biometric data from four African primate species.
AB  - BACKGROUND: Nonhuman primates are raised in large numbers in research centers and
      zoos. Reproductive monitoring is required to improve breeding performances.
      Ultrasonography is a safe method to determine gestational age and to estimate the
      date of parturition. However only few data are available in nonhuman primates.
      METHODS: Fetal biometric data were obtained throughout pregnancy on four African
      primate species, namely chimpanzee, gorilla, mandrill and patas monkey.
      Measurements included biparietal diameter, transverse abdominal diameter, femur
      and humerus length, external interorbital diameter, and fetal heart rate. Curves
      established from these data were compared with previously published data in
      chimpanzees and gorillas and with those for humans and other closely related
      primate species. RESULTS: The curves for the different hominids were very
      similar, while those for mandrills more closely resembled baboons and data for
      patas monkeys were comparable to those for macaques. CONCLUSIONS: These data, by
      providing a tool to evaluate precise gestational age, will be useful for centers
      raising these four primate species.

PMID- 16430495
TI  - Clinical, biochemical, and electrocardiographic aspects of Trypanosoma cruzi
      infection in free-ranging golden lion tamarins (Leontopithecus rosalia).
AB  - BACKGROUND: Wild golden lion tamarins from the Biological Reserve of Poco das
      Antas, Rio de Janeiro, Brazil, have high prevalence of Trypanosoma cruzi
      infection leading us to clinically assess the disease in this endangered species.
      METHODS: 34 tamarins were sampled for the presence of T. cruzi infection (through
      serology) and clinical evaluation (electrocardiography, blood counts and
      biochemical analysis). RESULTS: 32% of the sampled tamarins were T. cruzi
      positive, 45% of these displayed cardiac abnormalities. Main cardiac abnormality
      in infected tamarins was T wave low voltage; R wave low voltage and V3S wave high
      voltage were also found. The tamarins displaying T wave low voltage had high
      proportion of seric cardiac creatine kinase. Seric mean total protein was
      significantly higher in infected tamarins. CONCLUSIONS: Sampled tamarins
      displayed typical signs of T. cruzi infection, similar to experimentally infected
      primates and human natural infection. Potential risk of T. cruzi infection to
      this endangered species is discussed.

PMID- 16430498
TI  - Fungal tyrosinases: new prospects in molecular characteristics, bioengineering
      and biotechnological applications.
AB  - Tyrosinases are type-3 copper proteins involved in the initial step of melanin
      synthesis. These enzymes catalyse both the o-hydroxylation of monophenols and the
      subsequent oxidation of the resulting o-diphenols into reactive o-quinones, which
      evolve spontaneously to produce intermediates, which associate in dark brown
      pigments. In fungi, tyrosinases are generally associated with the formation and
      stability of spores, in defence and virulence mechanisms, and in browning and
      pigmentation. First characterized from the edible mushroom Agaricus bisporus
      because of undesirable enzymatic browning problems during postharvest storage,
      tyrosinases were found, more recently, in several other fungi with relevant
      insights into molecular and genetic characteristics and into reaction mechanisms,
      highlighting their very promising properties for biotechnological applications.
      The limit of these applications remains in the fact that native fungal
      tyrosinases are generally intracellular and produced in low quantity. This review
      compiles the recent data on biochemical and molecular properties of fungal
      tyrosinases, underlining their importance in the biotechnological use of these
      enzymes. Next, their most promising applications in food, pharmaceutical and
      environmental fields are presented and the bioengineering approaches used for the
      development of tyrosinase-overproducing fungal strains are discussed.

PMID- 16430499
TI  - Which are the polyphosphate accumulating organisms in full-scale activated sludge
      enhanced biological phosphate removal systems in Australia?
AB  - AIMS: To see if the compositions of the microbial communities in full scale
      enhanced biological phosphorus removal activated sludge systems were the same as
      those from laboratory scale sequencing batch reactors fed a synthetic sewage.
      METHODS: Biomass samples taken from nine full scale enhanced biological phosphate
      removal (EBPR) activated sludge plants in the eastern states of Australia were
      analysed for their populations of polyphosphate (polyP)-accumulating organisms
      (PAO) using semi-quantitative fluorescence in situ hybridization (FISH) in
      combination with DAPI (4'-6-diamidino-2-phenylindole) staining for polyP.
      RESULTS: Very few betaproteobacterial Rhodocyclus related organisms could be
      detected by FISH in most of the plants examined, and even where present, not all
      these cells even within a single cluster, stained positively for polyP with DAPI.
      In some plants in samples from aerobic reactors the Actinobacteria dominated
      populations containing polyP. CONCLUSIONS: The PAO populations in full-scale EBPR
      systems often differ to those seen in laboratory scale reactors fed artificial
      sewage, and Rhodocyclus related organisms, dominating these latter communities
      may not be as important in full-scale systems. Instead Actinobacteria may be the
      major PAO. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings illustrate how
      little is still known about the microbial ecology of EBPR processes and that more
      emphasis should now be placed on analysis of full-scale plants if microbiological
      methods are to be applied to monitoring their performances.

PMID- 16430500
TI  - Enhancing the antimicrobial effects of bovine lactoferrin against Escherichia
      coli O157:H7 by cation chelation, NaCl and temperature.
AB  - AIM: To evaluate the effect of NaCl, growth medium and temperature on the
      antimicrobial activity of bovine lactoferrin (LF) against Escherichia coli
      O157:H7 in the presence of different chelating agents. METHODS AND RESULTS: LF
      (32 mg ml(-1)) was tested against E. coli O157:H7 strain 3081 in Luria broth (LB)
      and All Purpose Tween (APT) broth with metal ion chelators sodium bicarbonate
      (SB), sodium lactate (SL), sodium hexametaphosphate (SHMP), ethylene diamine
      tetraacetic acid (EDTA) or quercetin at 0.5 and 2.5% NaCl at 10 and 37 degrees C.
      LF and the chelators were tested against four other E. coli O157:H7 strains in LB
      at 2.5% NaCl and 10 degrees C. LF alone was bacteriostatic against strains 3081
      and LCDC 7283 but other strains grew. Antimicrobial effectiveness of LF was
      reduced in APT broth but enhanced by SB at 2.5% NaCl and 10 degrees C where 4.0
      log(10) CFU ml(-1) inoculated cells were killed. EDTA enhanced antimicrobial
      action of the LF-SB combination. SL alone was effective against E. coli O157:H7
      but a reduction in its activity at 2.5% NaCl and 10 degrees C was reversed by LF.
      The combinations LF-SHMP and LF-quercetin were more effective at 37 degrees C and
      NaCl effects varied. CONCLUSIONS: LF plus SB or SL were bactericidal toward the
      same 3/5 E. coli O157:H7 strains and inhibited growth of the others at 2.5% NaCl
      and 10 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: The combination of LF
      with either SL or SB shows potential for reducing viability of E. coli O157:H7 in
      food systems containing NaCl at reduced, but growth permissive temperature.

PMID- 16430501
TI  - Expression of single-chain antibody against RgpA protease of Porphyromonas
      gingivalis in Lactobacillus.
AB  - AIMS: The monoclonal antibody 61BG1.3, recognizing the RgpA protease, has been
      reported to confer protection against recolonization by the periodontal pathogen
      Porphyromonas gingivalis in humans. The aim of this study was to express a
      functional scFv derived from the monoclonal antibody 61BG1.3 on the surface of
      Lactobacillus paracasei for potential use in the prevention or treatment of
      periodontal diseases. METHODS AND RESULTS: The scFv was fused to an E-tag and
      cloned in the Escherischia coli/Lactobacillus shuttle vector pLP501, which
      mediates surface expression of the scFv. FACS analysis using an anti-E-tag
      antibody revealed that the scFv was expressed on the surface of the transformed
      lactobacilli and binding of the scFv to RgpA was shown by ELISA. Lact. paracasei
      expressing the scFv against RgpA was able to agglutinate P. gingivalis whereas
      the Lact. paracasei expressing an irrelevant scFv fragment did not. Scanning
      electron microscopy demonstrated efficient binding of the lactobacilli expressing
      the scFv anti-RgpA to P. gingivalis. CONCLUSIONS: We have expressed a functional
      scFv antibody directed against the RgpA protease of P. gingivalis in
      Lactobacillus. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest a
      potential of Lactobacillus expressing scFvs against P. gingivalis to be used to
      combat periodontal disease.

PMID- 16430502
TI  - Survival of the biocontrol yeast Pichia anomala after long-term storage in liquid
      formulations at different temperatures, assessed by flow cytometry.
AB  - AIMS: Investigate the survival of liquid formulations of the biocontrol yeast
      Pichia anomala J121 at different temperatures, and develop a system for
      comparative studies of different storage conditions and formulations. METHODS AND
      RESULTS: The survival of P. anomala in liquid formulations with lactose, starch
      and trehalose amendments was measured during prolonged storage at temperatures
      ranging from -20 to +30 degrees C. The relative survival of the stored cells was
      rapidly estimated by flow cytometry. After 4 weeks incubation at 4 and 10 degrees
      C, 75-90% of the cells were viable, with no significant differences between the
      various formulations. Supplementing the storage buffer with lactose or trehalose
      increased the survival after longer incubations (8 and 12 weeks) at all
      temperatures (-20 to 30 degrees C). Trehalose was the most effective protectant
      at 20 and 30 degrees C (>20% viable cells after 12 weeks at 20 degrees C). The
      biocontrol activity was maintained after formulation and prolonged storage of P.
      anomala. CONCLUSIONS: The storage potential of liquid formulated P. anomala cells
      can be increased by supplementation with lactose or trehalose. The combination of
      a custom made incubation chamber and flow cytometry was suitable to evaluate
      stability of P. anomala formulations. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Liquid formulated P. anomala have a long shelf life. The developed test system
      can be used to study different formulations of other biocontrol agents.

PMID- 16430503
TI  - The stability of micro-organisms preserved in LENTICULE discs, demonstrated by
      repeat sample distributions of the EQUAL Scheme for Indicator Organisms (water
      microbiology).
AB  - AIMS: To demonstrate the stability of microorganisms preserved in LENTICULE
      discs, employed by the EQUAL Scheme for Indicator Organisms. METHODS AND RESULTS:
      Five sample batches containing several indicator organism parameters were each
      despatched in two separate distributions at intervals of up to 24 months apart. A
      comparison of participants' median counts and bar charts of their cumulated
      results was then made. CONCLUSIONS: The results demonstrated that LENTICULE discs
      provided a remarkably stable preparation format for the maintenance of viable
      organisms in reproducible numbers. SIGNIFICANCE AND IMPACT OF THE STUDY: Complex
      mixtures of organisms can be maintained in stable numbers for extended periods of
      time at a freezer temperature of -20 degrees C and satisfactorily transported
      without the requirement for cold chain conditions.

PMID- 16430504
TI  - Primers based on the rpf gene region provide improved detection of Xanthomonas
      axonopodis pv. citri in naturally and artificially infected citrus plants.
AB  - AIMS: To have a PCR-based detection method for Xanthomonas axonopodis pv. citri
      (Xac) using primers designed in a specific region of its genome. METHODS AND
      RESULTS: A Xac-specific region was identified inside the rpf gene cluster of
      strain IAPAR 306 in an analysis of its complete genomic sequence. Two primers
      were designed, Xac01 and Xac02, which, when used in a standard PCR assay, direct
      the amplification of a 581 bp fragment from DNA of strains belonging to Xac from
      different regions around the world including unusual American and Asian strains.
      This product was not observed when DNA from strains of the closely related X. a.
      aurantifolli and X. a. citrumelo were used as templates. Extracts prepared from
      28 xanthomonads of other species, and epiphytic bacteria isolated from citrus
      also failed to produce products with these primers. Amplification was obtained
      from cells grown in vitro, from extracts of both fresh and dried citrus canker
      lesions and from washes of inoculated but asymptomatic leaf surfaces. In
      sensitivity tests, this PCR technique detected as few as 100 cells. CONCLUSIONS:
      Primers Xac01 and Xac02 provide specific and sensitive detection of Xac in all
      citrus tissues where the pathogen is found. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This PCR-based diagnostic test is suitable for monitoring asymptomatic plants in
      areas where the bacteria is endemic, in plant quarantine and regulatory
      situations, and also for obtaining an accurate diagnosis in a very short time.
      These are important characteristics for any assay to be used for the management
      of citrus canker disease.

PMID- 16430506
TI  - Antimicrobial activity of essential oils and structurally related synthetic food
      additives towards selected pathogenic and beneficial gut bacteria.
AB  - AIMS: To assess the potential of essential oils and structurally related
      synthetic food additives in reducing bacterial pathogens in swine intestinal
      tract. METHODS AND RESULTS: The antimicrobial activity of essential
      oils/compounds was measured by determining the inhibition of bacterial growth.
      Among 66 essential oils/compounds that exhibited > or =80% inhibition towards
      Salmonellatyphimurium DT104 and Escherichia coli O157:H7, nine were further
      studied. Most of the oils/compounds demonstrated high efficacy against S.
      typhimurium DT104, E. coli O157:H7, and E. coli with K88 pili with little
      inhibition towards lactobacilli and bifidobacteria. They were also tolerant to
      the low pH. When mixed with pig cecal digesta, these oils/compounds retained
      their efficacy against E. coli O157:H7. In addition, they significantly inhibited
      E. coli and coliform bacteria in the digesta, but had little effect on the total
      number of lactobacilli and anaerobic bacteria. CONCLUSIONS: Some essential
      oils/compounds demonstrated good potential, including efficacy, tolerance to low
      pH, and selectivity towards bacterial pathogens, in reducing human and animal
      bacterial pathogens in swine intestinal tract. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study has identified candidates of essential oils/compounds for in
      vivo studies to develop antibiotic substitutes for the reduction of human and
      animal bacterial pathogens in swine intestinal tract.

PMID- 16430505
TI  - Growth dynamics of Azospirillum lipoferum at steady and transitory states in the
      presence of NH.
AB  - AIMS: The objective of this paper was to study the adaptation dynamics and
      biochemical response of Azospirillum lipoferum grown in a continuous culture at
      various environmental shifts. METHODS AND RESULTS: The kinetics of A. lipoferum
      Sp 59b grown at steady states in a microaerobic chemostatic environment deviated
      from a typical Monod kinetics in both low and high dilution rates (D) due to
      several metabolic shifts that occurred in the microbial cell. When NH4Cl was
      exhausted (at low D), the microbial cell partitioned carbon flow in order to
      sustain growth, nitrogen fixation and assimilation processes (occurred via the
      glutamate synthase reaction). Increasing D the specific activities of the enzymes
      involved in the tricarboxylic acid cycle and the respiration rate were decreased.
      At transitory states, under optimal for nitrogen fixation dissolved oxygen (DO)
      concentrations, ammonium nitrogen negatively affected, besides nitrogen fixing
      activity, the bacterial growth. At sub-optimal for nitrogen fixation DO
      concentration (i.e. 1.56 microM) and 0.1 g l(-1) NH4Cl in the fed medium, the
      activities of citrate synthase and succinate dehydrogenase were significantly
      reduced. CONCLUSIONS: Important shifts in both carbon and nitrogen metabolism
      occur in A. lipoferum grown in the presence of the ammonium nitrogen, while the
      boundaries of ammonium nitrogen concentration in which A. lipoferum can be
      adapted depend on the DO concentration in the growth environment. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Studies on growth dynamics and physiology of A.
      lipoferum, grown in experimental model systems, can contribute to an efficient
      application of these bacteria as plant-growth-promoting-agents.

PMID- 16430507
TI  - Use of a systematic review to assist the development of Campylobacter control
      strategies in broilers.
AB  - AIMS: Produce an evidence-based ranking of the major contributing factors and
      sources of Campylobacter occurrence in broilers produced in England, Scotland and
      Wales - Great Britain (GB). METHOD AND RESULTS: Relevant data were extracted from
      159 research papers and findings were grouped into 14 sources of on-farm
      contamination and 37 contributing factors. A relevancy score was developed to
      take into account various measures from each study of applicability to GB
      broilers and strength of findings. Results indicate that major sources of
      Campylobacter include a depopulation event, another house on-farm, on-farm staff,
      and other animals on farm. The depopulation schedule (staggered slaughter) and
      multiple houses on-farm were identified as contributing factors associated with
      increasing the risk, and those decreasing the risk were use of a hygiene barrier,
      parent company and certain seasons of rearing. CONCLUSIONS: Although the review
      was more resource intensive compared to narrative studies, the system allows an
      increased level of transparency and the ability to investigate patterns and
      trends. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper provides the first
      evidence-based ranking of the major sources and contributing factors for
      Campylobacter presence in broilers in GB using a systematic review.

PMID- 16430508
TI  - Phenon cluster analysis as a method to investigate epidemiological relatedness
      between sources of Campylobacter jejuni.
AB  - AIMS: To develop a method for assessing the relative epidemiological significance
      of possible infection sources for human campylobacteriosis. METHODS AND RESULTS:
      Using fluorescent amplified fragment length polymorphism (AFLP), 243 apparently
      epidemiologically unrelated Campylobacter jejuni isolates were genotyped (77
      human, 46 cattle, 49 pet and 71 poultry isolates). In total 136 different phena
      were identified, of which 48 were clusters grouping at least two isolates.
      Isolates from different sources were frequently clustered together, underlining
      the high degree of source mixing and the lack of host specificity of C. jejuni.
      The phena were classified into different phenon types according to the sources of
      the isolates they contained. The occurrence of these phenon types was analysed
      using an area-proportional Euler diagram to describe epidemiological relatedness
      among C. jejuni isolates. Group separation statistics revealed that 43% of
      analysed human isolates expressed maximum similarity to other human isolates, 9%
      to cattle isolates, 21% to pet isolates and 27% to poultry isolates; these
      results were in accordance with the pattern observed in the phenon cluster
      analysis. CONCLUSIONS: Based on the grouping of strains into molecular similarity
      clusters, ecological patterns between sources can be investigated. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This approach is a new methodological contribution to
      establish the relative epidemiological significance of concurrent infection
      sources.

PMID- 16430509
TI  - Enhanced biodegradation of diesel oil by a newly identified Rhodococcus
      baikonurensis EN3 in the presence of mycolic acid.
AB  - AIMS: The aim of the present study was to isolate and characterize a bacterium,
      strain EN3, capable of using diesel oil as a major carbon and energy source, and
      to analyse the enhancement of diesel oil degradation by this organism using
      synthetic mycolic acid (2-hexyl-3-hydroxyldecanoic acid). METHOD AND RESULTS: An
      actinomycete with the ability to degrade diesel oil was isolated from oil
      contaminated soil and characterized. The strain had phenotypic properties
      consistent with its classification in the genus Rhodococcus showing a 16S rRNA
      gene similarity of 99.7% with Rhodococcus baikonurensis DSM 44587(T). The ability
      of the characterized strain to degrade diesel oil at various concentrations
      (1000, 5000, 10 000 and 20 000 mg l(-1)) was determined. The effect of synthetic
      mycolic acid on the biodegradation of diesel oil was investigated at the 20 000
      mg l(-1) concentration; the surfactant was added to the flask cultures at three
      different concentrations (10, 50 and 100 mg l(-1)) and degradation followed over
      7 days. Enhanced degradation was found at all three concentrations of the
      surfactant. In addition, the enhancement of diesel oil degradation by other
      surfactants was observed. CONCLUSIONS: The synthetic mycolic acid has potential
      for the remediation of petroleum-contaminated sites from both an economic and
      applied perspective as it can stimulate biodegradation at low concentrations.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed that the synthesized
      mycolic acid can be used for potential applications in the bioremediation
      industries, for example, in oil spill clean-up, diesel fuel remediation and
      biostimulation.

PMID- 16430510
TI  - Phages of Lactobacillus casei/paracasei: response to environmental factors and
      interaction with collection and commercial strains.
AB  - AIM: To investigate the influence of several environmental factors on the
      viability and cell-adsorption for two Lactobacillus casei/paracasei
      bacteriophages (PL-1 and J-1). METHODS AND RESULTS: Both phages showed a
      remarkably high specificity of species, sharing similar host spectra. Two phages
      and four sensitive strains were used to conform five phage/strain systems. Each
      showed a particular behaviour (burst size: ranging from 32 to 160 PFU/infective
      centre; burst time: 120-240 min and latent time: 5-90 min). For both phages, the
      viability was not significantly affected from pH 4 to 11 (room temperature) and
      from pH 5 to 10 (37 degrees C). Adsorption rates were not influenced by calcium
      ions, but decreased after the thermal inactivation of cells. Adsorption rates
      were high between 0 and 50 degrees C with maximum values at 30 degrees C and pH
      6. System PL-1/Lact. paracasei A showed noticeable differences in comparison with
      the others, being times required to reach 90% of adsorption of 4 h and lower than
      45 min, respectively. CONCLUSIONS: The data obtained in this work demonstrated
      that environmental parameters can influence the viability and cell adsorption
      rates of Lact. casei/paracasei phages. The extent of this influence was phage
      dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: This work contributes to the
      enlargement of the currently scarce knowledge of phages of probiotic bacteria.

PMID- 16430511
TI  - Identification of a DNA restriction-modification system in Pectobacterium
      carotovorum strains isolated from Poland.
AB  - AIMS: Polish isolates of pectinolytic bacteria from the species Pectobacterium
      carotovorum were screened for the presence of a DNA restriction-modification (R
      M) system. METHODS AND RESULTS: Eighty-nine strains of P. carotovorum were
      isolated from infected potato plants. Sixty-six strains belonged to P.
      carotovorum ssp. atrosepticum and 23 to P. carotovorum ssp. carotovorum. The
      presence of restriction enzyme Pca17AI, which is an isoschizomer of EcoRII
      endonuclease, was observed in all isolates of P. c. atrosepticum but not in P. c.
      carotovorum. The biochemical properties, PCR amplification, and sequences of the
      Pca17AI restriction endonuclease and methyltransferase genes were compared with
      the prototype EcoRII R-M system genes. Only when DNA isolated from cells of P. c.
      atrosepticum was used as a template, amplification of a 680 bp homologous to the
      gene coding EcoRII endonuclease. CONCLUSIONS: Endonuclease Pca17AI, having a
      relatively low temperature optimum, was identified. PCR amplification revealed
      that the nucleotide sequence of genes for EcoRII and Pca17AI R-M are different.
      Dcm methylation was observed in all strains of Pectobacterium and other Erwinia
      species tested. The sequence of a DNA fragment coding Dcm methylase in P.
      carotovorum was different from that of Escherichia coli. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Pca17AI is the first psychrophilic isoschizomer of EcoRII
      endonuclease. The presence of specific Dcm methylation in chromosomal DNA
      isolated from P. carotovorum is described for the first time. A 680 bp PCR
      product, unique for P. c. atrosepticum strains, could serve as a molecular marker
      for detection of these bacteria in environmental samples.

PMID- 16430512
TI  - PCR-based procedures for detection and quantification of Staphylococcus aureus
      and their application in food.
AB  - AIMS: To evaluate the specificity of nuc targeted primers for PCR detection of
      Staphylococcus aureus in different food matrices and to establish a RTQ-PCR
      procedure suitable for the routine detection and quantification of this pathogen
      in food. METHODS AND RESULTS: Specificity of nuc targeted primers (Pri1-Pri2 and
      the newly designed RTQ-PCR primers) was tested on a total of 157 strains of
      genetically confirmed identity, including reference and food isolates. PCR
      detection on artificially inoculated beef samples by DNA extraction using a
      DNeasy Tissue Kit (Qiagen GmhH, Hilden, Germany) showed a sensitivity value
      around 10(3) CFU g(-1). The two RTQ-PCR systems, incorporating SYBR-Green I and
      TaqMan, respectively, applied in the present work improved the sensitivity of
      conventional PCR by lowering the detection level to 10 and 100 cells,
      respectively. Out of 164 naturally contaminated foods tested for the presence of
      Staph. aureus, 74 were positive by conventional PCR and 69 by the traditional
      culture method with a high degree of result agreement between both methodologies
      (93.3%). CONCLUSIONS: PCR approaches, using nuc targeted primers, have proved
      specific and combined with growth techniques may improve detection of Staph.
      aureus in different types of food. SIGNIFICANCE AND IMPACT OF THE STUDY: The SYBR
      Green I real-time PCR approach established allows the sensitive, automated and
      quantitative detection of Staph. aureus for routine analysis at a reasonable
      cost.

PMID- 16430513
TI  - Soil inactivation of DNA viruses in septic seepage.
AB  - AIMS: To generate field-relevant inactivation data for incorporation into models
      to predict the likelihood of viral contamination of surface waters by septic
      seepage. METHODS AND RESULTS: Inactivation rates were determined for PRD1
      bacteriophage and Adenovirus 2 in two catchment soils under a range of
      temperature, moisture and biotic status regimes. Inactivation rates presented for
      both viruses were significantly different at different temperatures and in
      different soil types (alpha = 0.05). Soil moisture generally did not
      significantly affect virus inactivation rate. Biotic status significantly
      affected inactivation rates of PRD1 in the loam soil but not the clay-loam soil.
      Adenovirus 2 was inactivated more rapidly in the loam soil than PRD1
      bacteriophage. CONCLUSIONS: Virus inactivation rates incorporated into models
      should be appropriate for the climate/catchment in question with particular
      regard to soil type and temperature. Given that PRD1 is similar in size to
      adenoviruses, yet more conservative with regard to inactivation in soil, it may
      be a useful surrogate in studies of Adenovirus fate and transport. SIGNIFICANCE
      AND IMPACT OF THE STUDY: A better understanding of the factors that govern virus
      fate and transport in catchments would facilitate the design of barrier measures
      to prevent viral contamination of surface waters by septic seepage.

PMID- 16430514
TI  - Development of a magnetic capture hybridization-PCR assay for Listeria
      monocytogenes direct detection in milk samples.
AB  - AIMS: A rapid and sensitive method for Listeria monocytogenes direct detection
      from milk was developed. It is based on a magnetic capture hybridization
      procedure for selective DNA purification, followed by PCR identification. A
      comparison with two similar commercial systems from Dynal (Dynabeads) was carried
      out. METHODS AND RESULTS: The technique used previously developed nanoparticles
      modified with a 21-mer oligonucleotide. This sequence, sharing homology with all
      the L. monocytogenes strains, was selected on hlyA gene and located outside the
      desired specific PCR site to avoid cross-contaminations. Capture probe
      properties, in term of spacer length and purification, were determined to obtain
      the highest hybridization efficiency. Its specificity was tested in hybridization
      experiments with nontarget bacterial species. Any inhibitory effect of the
      nanoparticles on PCR was also examined. The amplification performed with the
      purified DNA could reliably identify a 10 CFU ml(-1) contamination rate.
      CONCLUSIONS: The optimized purification method showed a high specificity and
      sensitivity, with a detection level one log more sensitive than PCR carried out
      with nucleic acids obtained using commercial nanoparticles. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The method, avoiding pre-enrichment, provides a rapid
      alternative to conventional microbiological detection methods. Furthermore, it is
      suitable for automation and can be proposed for the screening of a large number
      of samples.

PMID- 16430515
TI  - Escherichia coli with anti-O157:H7 activity isolated from bovine colon.
AB  - AIMS: To isolate bacteria from bovine gastrointestinal tract and investigate
      their inhibitory effect on Escherichia coli O157:H7 in vitro. METHODS AND
      RESULTS: A total of 2400 bacterial colonies were isolated from cattle colonic
      mucous membrane. Thirteen strains demonstrated the ability to inhibit the growth
      of E. coli O157:H7. From these, seven were screened for the presence of virulence
      factors as: stx(1), stx(2), ehxA, eae, st1a and lt1 by polymerase chain reaction.
      The selected bacteriocin-producing bacteria showed susceptibility to most of the
      antibiotics used. CONCLUSIONS: The strains of E. coli isolated, which exhibit
      inhibitory activity on E. coli O157:H7 growth by the production of inhibitory
      substances, may be useful in the control of this pathogen in reservoirs. An
      important characteristic of these strains was the absence of any of the virulence
      factors assayed and the susceptibility to most of the antibiotics used for Gram
      negative bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: These microorganisms
      might be used as probiotic bacteria to reduce the carriage of E. coli O157:H7 in
      cattle, thus limiting the contamination of carcasses at slaughter and
      subsequently the contamination of foods and the transfer of this pathogen to man.

PMID- 16430516
TI  - Effect of amino acids containing sulfur on dithiolopyrrolone antibiotic
      productions by Saccharothrix algeriensis NRRL B-24137.
AB  - AIMS: To study the effect of sulfur-containing amino acids (L-cysteine, L
      cystine, L-methionine and DL-ethionine) on the production of dithiolopyrrolone
      antibiotics by Saccharothrix algeriensis NRRL B-24137. METHODS AND RESULTS: The
      production levels of dithiolopyrrolones were investigated by using high
      performance liquid chromatography in a chemically semi-synthetic medium. The
      production of the studied antibiotics depends upon the nature, concentration and
      the time of addition of these sources in the culture medium. Both cysteine and
      cystine favoured the specific productions of dithiolopyrrolones; iso-butyryl
      pyrrothine (ISP) by cysteine, however butanoyl-pyrrothine, senecioyl-pyrrothine
      and tigloyl-pyrrothine by cystine, when added initially to the culture medium.
      The maximum specific productions of dithiolopyrrolones were observed in the
      presence of 5 mmol l(-1) cystine for thiolutin, 5 mmol l(-1) cysteine for ISP,
      and 10 mmol l(-1) cystine for others studied dithiolopyrrolones as shown in Fig.
      3. The production of these antibiotics was decreased when the concentrations of
      cysteine and cystine were in excess. All dithiolopyrrolone specific productions
      were strongly inhibited by addition of methionine and ethionine, without
      inhibition of mycelial growth. CONCLUSIONS: Among all studied amino acids,
      cystine and cysteine can be used as supplements for improvement the production of
      dithiolopyrrolone antibiotics by S. algeriensis NRRL B-24137. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Dithiolopyrrolone antibiotics have many important
      applications for employing them as medicaments, particularly in the treatment of
      human and animal cancers. In the present work, the influence of containing-sulfur
      amino acids on dithiolopyrrolone antibiotic productions was studied. The obtained
      results can be employed for the optimization of the culture medium for the
      dithiolopyrrolone productions in higher quantities.

PMID- 16430517
TI  - Characterization of the brewery spoilage bacterium Obesumbacterium proteus by
      automated ribotyping and development of PCR methods for its biotype 1.
AB  - AIMS: To study the ability of automated ribotyping to characterize
      Obesumbacterium proteus and Hafnia alvei, to design primers and to evaluate
      standard end-point and real-time PCR for the detection of O. proteus biotype 1 in
      beer and in brewers's yeast-containing samples. METHODS AND RESULTS: Automated
      ribotyping was carried out using the standard method with EcoRI and PvuII. The
      digestions with both enzymes clearly differentiated O. proteus biotypes 1 and 2
      and H. alvei. PCR primers were designed according to the 16S rRNA gene sequence
      of the O. proteus type strain. Two primer sets (Obs137-Obs558 and Obs137-Obs617)
      detected O. proteus biotype 1 and H. alvei but not O. proteus biotype 2 or other
      tested beer spoilage bacteria (40 species) in the end-point and real-time PCR,
      indicating their high specificity. The detection limit for O. proteus was 160
      1600 CFU 100 ml(-1) beer in the end-point PCR reactions and < or =160 CFU 100 ml(
      1) beer in the real-time PCR reactions. More cells (from 16 to 3200) were needed
      for detection in the presence of brewer's yeast cells. CONCLUSIONS: Automated
      ribotyping is a useful tool to characterize and identify O. proteus and H. alvei
      isolates. The designed primers are suitable for the rapid detection of O. proteus
      biotype 1 and H. alvei in brewery samples by PCR. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Automated ribotyping and PCR could improve microbiological quality control
      in breweries by facilitating the detection, identification and tracing of
      spoilage bacteria.

PMID- 16430518
TI  - In vitro fermentation of sugar beet arabinan and arabino-oligosaccharides by the
      human gut microflora.
AB  - AIMS: To determine the fermentation profiles by human gut bacteria of arabino
      oligosaccharides of varying degree of polymerization. MATERIALS AND METHODS:
      Sugar beet arabinan was hydrolyzed with a commercial pectinase and eight
      fractions, of varying molecular weight, were isolated by gel-filtration
      chromatography. Hydrolysis fractions, arabinose, arabinan and fructo
      oligosaccharides were fermented anaerobically by gut bacteria. Total bacteria,
      bifidobacteria, bacteroides, lactobacilli and the Clostridium
      perfringens/histolyticum sub. grp. were enumerated using fluorescent in situ
      hybridization. RESULTS: Bifidobacteria were stimulated to different extents
      depending on molecular weight, i.e. maximum increase in bifidobacteria after 48 h
      was seen on the lower molecular weight fractions. Lactobacilli fluctuated
      depending on the initial inoculum levels. Bacteroides numbers varied according to
      fraction; arabinan, arabinose and higher oligosaccharides (degree of
      polymerization, dp > 8) resulted in significant increases at 24 h. Only
      carbohydrate mixtures with dp of 1-2 resulted in significant increases at 48 h
      (log 8.77 +/- 0.23). Clostridia decreased on all substrates. CONCLUSIONS: Arabino
      oligosaccharides can be considered as potential prebiotics. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Arabinan is widely available as it is a component of sugar
      beet pulp, a co-product from the sugar beet industry. Generation of prebiotic
      functionality from arabinan would represent significant added value to a
      renewable resource.

PMID- 16430520
TI  - Capnocytophaga in the dental plaque of immunocompromised children with cancer.
AB  - OBJECTIVES: (i) To compare the prevalence and levels of Capnocytophaga, a known
      systemic pathogen in immunocompromised patients, in the dental plaque of healthy
      children and children with cancer, and (ii) to determine the susceptibility of
      strains isolated from cancer patients to a range of antibiotics. PATIENTS AND
      METHODS: Thirty-one children with cancer undergoing a first course of
      immunosuppressive chemotherapy and 30 healthy control children were included in
      the study. Samples were collected on days 0, 7, 14, and 21 of the cure (and
      equivalent dates in controls). Susceptibility to antibiotics was tested using an
      agar dilution method and galleries with predefined concentrations of selected
      antibiotics. RESULTS: There was a significant drop in the total anaerobic
      cultivable flora on day 14 and in the prevalence of Capnocytophaga on days 14 and
      21 in the children with cancer. The proportion of Capnocytophaga in the anaerobic
      flora, however, was high in certain cancer patients. Beta-lactam/beta-lactamase
      inhibitor combinations, imipenem, clindamycin, and tetracycline were the most
      effective against Capnocytophaga. CONCLUSION: This study showed that
      Capnocytophaga decreased in prevalence and proportion in the dental plaque of
      cancer patients during chemotherapy but became predominant in some cases. It is
      recommended that imipenem or beta-lactam/beta-lactamase inhibitor combinations be
      used to treat Capnocytophaga bacteraemia.

PMID- 16430521
TI  - A sociodental approach to assessing dental needs of children: concept and models.
AB  - OBJECTIVES: Traditional normative methods of assessing dental needs do not
      correspond to current concepts of 'health' and 'need'. Although there is dental
      research on quality of life, evidence-based practice, and oral behaviours, those
      concepts are rarely applied to dental needs estimation. Dental needs are usually
      calculated mainly from clinical data and are likely to be inaccurate. A
      structured comprehensive method for assessing dental needs is required. The
      objectives of this study are to develop and test a new sociodental system of
      needs assessment for overall dental needs of primary schoolchildren. Furthermore,
      normative and sociodental estimates of need are compared. DESIGN: The study
      developed a theoretical framework and pathway algorithms of sociodental needs
      assessment and applied them to assessing overall dental needs. Normative dental
      needs were assessed using standard normative criteria. The child oral impacts on
      daily performances (Child-OIDP) was used to assess oral impacts, and a self
      administered questionnaire was used to obtain information on demographic
      variables and oral behaviours. Data were analysed according to the developed
      algorithms. SETTING: A cross-sectional survey in Suphanburi Province, Thailand.
      PARTICIPANTS: All 1,126 children aged 11-12 years in a town. MAIN RESULTS: The
      sociodental approach was acceptable and not costly. In all, 54.4% had normative
      need under the dental needs model for life-threatening and progressive
      conditions, but only 16.6% had high propensity-related need; the remaining 37.8%
      would require dental health education or oral health promotion (DHE/OHP) or both
      and appropriately adjusted clinical interventions. Under the basic model of
      dental needs, 45.1% had normative need. Two-thirds of them (30.9%) had impact
      related need and the remaining 14.2% did not have oral impacts and therefore
      should only receive dental health education. Only one-third of those with impact
      related need had high propensity and were suitable for evidence-based
      conventional treatments; the remaining two-thirds should receive DHE/OHP and
      alternative clinical interventions. CONCLUSIONS: A sociodental system of dental
      needs assessment was developed and tested on school children. It decreased the
      estimates of conventionally assessed dental treatment needs and introduced a
      broader approach to care.

PMID- 16430522
TI  - A survey of specialist paediatric dental services in Sweden: results from 2003,
      and trends since 1983.
AB  - The child population in Sweden has changed dramatically during the last 20 years.
      Changes have also occurred within the Public Dental Service (PDS), regarding the
      provision of dental care to children and adolescents. All these changes may
      affect the referral pattern and provision of specialist dental care for children
      and adolescents. OBJECTIVES: The primary aim of this study was to survey the
      services provided by specialists in paediatric dentistry in Sweden during 2003. A
      secondary aim was to compare the results with previous surveys. METHODS: A Web
      based survey was sent to all 34 specialist paediatric dentistry clinics and was
      answered by all clinics. Data were compared with results from the surveys
      performed in 1983, 1989, and 1996. RESULTS: The number of paediatric dentists had
      been relatively constant over the last 20 years, whereas the number of children
      referred to paediatric dentists had increased by 28% since 1983. It was estimated
      that 1.3% of all children in Sweden are treated at a specialist paediatric dental
      clinic in 2003. Dental treatment need in combination with behaviour management
      problems (BMP) was the main reason for referral and occurred in 37% of all
      referrals. The proportion of medically compromised children/children with
      disabilities had increased from 6% in 1983 to 22% in 2003. The number of patients
      treated using sedation and general anaesthesia had increased since 1983, and
      particularly since 1996. CONCLUSIONS: Despite improvements in dental health among
      children and adolescents in Sweden during the last 20 years, an increasing number
      of children are referred for specialist paediatric dental treatment. There is an
      urgent need to increase the number of specialist paediatric dentists in Sweden in
      order to ensure the continuation of high quality of dental care for children and
      adolescents.

PMID- 16430523
TI  - Sociodemographic and behavioural correlates of severe dental fluorosis.
AB  - OBJECTIVES: The aim of this study was to identify sociodemographic and
      behavioural factors associated with the prevalence of severe dental fluorosis in
      moderate- and high-fluoride areas of the Ethiopian Rift Valley. METHODS: Three
      hundred and six adolescents (12-15 years) and 233 mothers participated in the
      study. The children were examined for dental fluorosis according to the Thylstrup
      Fejerskov Index (TFI). The children and their mothers were subsequently
      interviewed. Sixty mothers had more than one participating child. In order to
      perform a paired parent/child analysis, a total of 73 younger siblings had to be
      excluded. RESULTS: Among the remaining 233 children, the prevalence of severe
      dental fluorosis (TFI >or= 5) was 24.1% and 75.9% in the moderate- and high
      fluoride areas, respectively. According to bivariate as well as multivariate
      analyses, a number of sociodemographic and behavioural factors were related to
      severe fluorosis. The odds for having severe fluorosis varied according to the
      fluoride concentration of the drinking water, age, consumption of tea, length of
      breastfeeding and method of storing water. The adjusted odds ratios ranged from
      2.6 to 26.1. Breastfeeding for > 18 months and the use of clay pots for storing
      drinking water helped protect against severe dental fluorosis. Bivariate analyses
      indicated that being male and consuming fish might be associated with higher TFI
      scores. CONCLUSION: In order to avoid dental fluorosis, low-fluoride drinking
      water should be provided in the relevant villages. A prolonged period of
      breastfeeding, the use of clay pots for storing water, and possibly a reduced
      intake of tea and whole fish in infants might also help to avoid severe fluorosis
      in children growing up in traditionally fluoride-endemic areas.

PMID- 16430524
TI  - Mixed dentition space analysis in a Jordanian population: comparison of two
      methods.
AB  - AIMS: To test the reliability of the Moyers charts and the Tanaka and Johnston
      equations in Jordanians and to derive coefficients of correlation between the
      combined mesiodistal widths of the four permanent mandibular incisors and the
      combined widths of the canine and premolars of the maxillary and mandibular
      quadrants. METHODS: The dental models of the dentition of 130 male and 96 female
      Jordanian subjects (age range is 14-16 years) with complete permanent dentition
      were randomly selected. The mesiodistal width of the four permanent mandibular
      incisors, maxillary and mandibular canines, and premolar teeth were measured
      using a vernier gauge caliper to the nearest 0.1 mm. The actual teeth
      measurements were then compared with the predicted values derived from the Tanaka
      and Johnston equations and Moyers probability tables. Correlation and linear
      regression analyses were performed between the predicted and actual tooth size
      for Jordanian children and standard regression equations were developed. RESULTS:
      Except for the maxillary arch in male subjects, Tanaka and Johnston regression
      equations underestimated the mesiodistal widths of permanent canines and
      premolars. On the other hand, there were no statistically significant differences
      between actual mesiodistal widths of canines and premolars and the predicted
      widths from Moyers charts at the 65% and 75% level for the lower and upper arches
      in male subjects and at the 85% level for the upper and lower arches in female
      subjects. For the newly developed regression equations, the correlation
      coefficients between the sum of the mandibular four incisors and the sum of the
      canine and premolars were 0.60 (for lower) and 0.51 (for upper) in male subjects
      and 0.59 and 0.64, respectively, in female subjects. CONCLUSIONS: (1) Tanaka and
      Johnston prediction method was not accurate when applied to a Jordanian
      population. (2) Moyers method for prediction can be used for Jordanian children
      at different probability levels for male and female subjects.

PMID- 16430525
TI  - Fluoride content of bottled waters available in Northern Greece.
AB  - OBJECTIVE: The aim of this study was to evaluate the fluoride content of bottled
      drinking waters commercially available in northern Greece and to report on the
      accuracy of the labelling of fluoride concentration. MATERIALS AND METHODS:
      Twenty-two randomly selected commercial brands of bottled water were obtained
      from three supermarkets in Thessaloniki, Greece. Three bottles of each brand were
      purchased. Following calibration, six tests were conducted on each bottle using a
      combination fluoride-ion selective electrode (Orion, 96-09-00, MA, USA). The
      average reading for each brand was estimated and also compared with the fluoride
      content printed on the label. RESULTS: The mean (+/- SD) fluoride content of the
      bottled water samples was 0.35 (+/- 1.00) mg F/L with a range from 0.05 to 4.8 mg
      F/L. Only 18% (N = 4) of brands tested mention the fluoride concentration on the
      label, and 90% (N = 22) had a tested fluoride between 0.05 and 0.21 mg F/L. Of
      the remaining two brands, one was found to contain 0.3 mg F/L without having the
      fluoride concentration indicated on the label, and the other was labelled at 6 mg
      F/L, whereas the concentration was estimated as 4.8 mg F/L. CONCLUSIONS: The use
      of bottled water may be a significant source of systemic fluoride and therefore
      be considered as a risk factor for dental fluorosis in young children. This
      article shows that bottled drinking waters contain differing concentrations of
      fluoride. The manufacturers' labelling of fluoride concentrations may be
      inaccurate. When prescribing fluoride supplements, dentists should be aware of
      the fluoride content of bottled waters used by paediatric patients, especially
      brands with a concentration higher than 0.3 mg F/L. In view of the wide variation
      of fluoride concentration in the tested bottled waters, regulatory guidelines for
      controlling concentration in order to prevent dental fluorosis are recommended.

PMID- 16430527
TI  - Solitary median maxillary central incisor and normal stature: a report of three
      cases.
AB  - Solitary median maxillary central incisor (SMMCI) is a rare finding. Growth
      deficiency or other systemic abnormalities may or may not be seen in children
      with this anomaly. Nevertheless, the growth and development of all children with
      SMMCI should be closely monitored. This article reports the dental findings of
      three Chinese girls with SMMCI, but no growth deficiency or other systemic
      involvement.

PMID- 16430526
TI  - Is there life after Buckley's Formocresol? Part I -- a narrative review of
      alternative interventions and materials.
AB  - OBJECTIVES: (1) To present a narrative review of the currently available
      alternative interventions and materials to formocresol pulpotomy for the
      management of extensive caries in the primary molar, and (2) to produce a
      clinical protocol for pulp therapy techniques in the extensively carious primary
      molar. INTRODUCTION: The International Agency for Research on Cancer has recently
      classified formaldehyde as carcinogenic to human beings. Since Buckley's
      Formocresol contains 19% formaldehyde in its full strength and, therefore, 1% in
      a 20% dilution, a safer alternative should be identified. METHODS: A narrative
      review of the published literature for primary molar pulp therapy techniques was
      undertaken following an extensive and appropriate literature search. A specialist
      group of paediatric dentists was formed to arrive at a consensus and establish an
      evidence-based protocol for the management of extensively carious primary molar
      teeth. Part I of this paper explores the currently available alternative
      interventions and materials to formocresol in the form of a narrative review. The
      second part of the paper will present the formation of a specialist group to
      arrive at a consensus and establish an evidence-based protocol for the management
      of the extensively carious primary molar. CONCLUSIONS: After consideration of a
      review of extensively searched literature, a protocol and key points document
      have been developed to assist clinicians in their treatment planning. Further
      long-term studies with the highest level of evidence (i.e. randomized controlled
      trials) are required to enable us to identify acceptable alternatives which can
      replace formocresol.

PMID- 16430528
TI  - Dental abscess in a tooth with intact dens evaginatus.
AB  - This article reports a case of dental abscess in a mandibular premolar with
      intact dens evaginatus. Dentists are advised to critically evaluate those teeth
      with dens evaginatus, both clinically and radiographically, before attempting
      prophylactic treatments. This is particularly important medicolegally in case the
      tooth develops symptoms shortly after the prophylactic treatment. Dentists
      practising in Western countries should also be aware of this dental anomaly
      because of the increasing global migration of people from Asia.

PMID- 16430529
TI  - Dental findings of a child with Wolf-Hirschhorn syndrome.
AB  - The case presented is that of a 5-year-old female with Wolf-Hirschhorn syndrome.
      Dental findings were severe hypodontia, late dental development, taurodontism of
      the primary molars, microdontia, and spacing. Hypodontia has previously been
      reported and therefore this case adds to the evidence that hypodontia may be a
      common feature of this syndrome. It also suggests that other dental anomalies
      could occur in children with Wolf-Hirschhorn syndrome.

PMID- 16430530
TI  - Sotos syndrome with hypodontia.
AB  - Sotos syndrome, or cerebral gigantism, is a rare genetic condition characterized
      by tall stature, gigantism, dolichocephaly, advanced bone age and learning
      disability. The purpose of this case report is to highlight the dental management
      of a 10-year-old boy with Sotos syndrome who presented with hypodontia and dental
      caries.

PMID- 16430531
TI  - Dental follicle infection following a dog bite.
AB  - Animal bite wounds and their subsequent infection are relatively common.
      Incidence rates for dog bites are significantly higher among children aged 0-9
      years, especially among boys. Although bite wounds may initially look innocuous,
      they frequently lead to serious infection with a potential for life-threatening
      complications. The microbiology of dog bite wounds is usually polymicrobial,
      typically including anaerobes, Staphylococcus aureus and Pasteurella species. A
      case is described of a 22-month-old boy who, subsequent to a dog bite over the
      left maxilla, suffered infection of the dental follicle of the primary maxillary
      canine with Pasteurella multocida. The infection proved difficult to treat,
      requiring several attempts at incision and drainage of the abscess together with
      systemic antibiotics, and resulted in the eventual loss of the tooth.

PMID- 16430532
TI  - Clonidine in paediatric anaesthesia: review of the literature and comparison with
      benzodiazepines for premedication.
AB  - BACKGROUND: Children undergoing anaesthesia and surgery can experience
      significant anxiety and distress during the peri-operative period, but whether
      routine premedication is necessary is currently debated. Benzodiazepines are the
      most frequently used drugs as premedication in paediatric anaesthesia. In the US,
      50% of young children undergoing surgery receive premedication and midazolam is
      the most frequently used drug in this context (1). Nishina and coworkers (2)
      concluded in a review article in 1999 that clonidine, administered via an oral,
      rectal, or caudal route, is a promising adjunct to anaesthetics and analgesics to
      enhance quality of peri-operative management in infants and children. Later
      publications also support the use of clonidine for premedication (3-6). The aim
      of this communication is to review the use of clonidine in paediatric anaesthesia
      and to propose clonidine as a promising alternative to midazolam. Clonidine is
      associated with a number of beneficial effects in the context ofanaesthesia both
      in adults and children. Why clonidine is not routinely use in clinical practice
      despite the massive publication list is to a large extent due to the lack of
      marketing efforts from the pharmaceutical industry since multiplegeneric
      preparations are now readily available on most markets. Midazolam is also
      associated with a number of beneficial effects, but is far from an ideal
      premedicant in children, especially with regards to the amnesia, confusion and
      long term behavioural disturbances. Clonidine has contrary to midazolam no effect
      on respiration. We believe that clonidine is a good alternative to midazolam as
      premedication in infants and children.

PMID- 16430533
TI  - Midazolam depresses carotid body chemoreceptor activity.
AB  - BACKGROUND: Although the contribution of the gamma-aminobutyric acid (GABA)
      receptor system in peripheral chemosensation is unclear, immunohistochemistry has
      demonstrated the presence of GABA-ergic receptors in mammalian carotid bodies. We
      hypothesized that an activation of the carotid body GABA receptors would
      counteract the depolarizing effect of hypoxia. METHODS: The carotid body with
      arterial supply and the carotid sinus nerve was removed en bloc from New Zealand
      White rabbits and placed in a perfusion chamber. The carotid body preparation was
      perfused via the cut common carotid artery with a modified Tyrode's solution at a
      rate of 3.5-4.5 ml/min with a constant pressure of 45 cmH2O. The carotid sinus
      nerve firing frequency (Hz) was recorded at two different oxygen tension levels
      during perfusion with midazolam of 1, 10 and 100 microg/l. RESULTS: The frequency
      was decreased by midazolam in a dose-dependent manner (n = 8). Firing frequencies
      (mean +/- SEM) at the low oxygen tension level decreased from 643.13 +/- 67.2 Hz
      in the control to 554.5 +/- 67.7 Hz (P = 0.054 vs. control), 509.01 +/- 100.5 Hz
      (P < 0.012 vs. control) and 422.6 +/- 77.3 Hz (P < 0.001 vs. control) during
      perfusion with midazolam of 1, 10 and 100 microg/l, respectively. CONCLUSION:
      Midazolam depresses carotid body chemoreceptor activity in a dose-dependent
      manner.

PMID- 16430534
TI  - Ischemic preconditioning attenuates the lipid peroxidation and remote lung injury
      in the rat model of unilateral lower limb ischemia reperfusion.
AB  - BACKGROUND: Ischemia and reperfusion of the skeletal muscle tissue may cause
      remote lung injury. We aimed to evaluate the protective effect of ischemic
      preconditioning (IP) on the lung during unilateral lower limb ischemia
      reperfusion (IR). METHODS: Four groups of rats were used in this study: (i) the
      sham group (sham, n = 6) served as time controls, they remained anesthetized for
      the whole duration of the study; (ii) the ischemia and reperfusion group (IR, n =
      10) underwent 4 h of left lower limb ischemia followed by 2 h of reperfusion;
      (iii) the ischemic preconditioning group (IP, n = 10), the left lower limbs of
      rats were exposed to three cycles of IP (10 min of ischemia followed by 10 min of
      reperfusion); and (iv) the ischemic preconditioning plus ischemia reperfusion
      group (IP/IR, n = 10) underwent IP followed by IR as in the IP and IR groups.
      Plasma and tissue samples were taken at the end of the study period for
      determination of lung tissue myeloperoxidase activity (MPO) and polymorphonuclear
      leukocyte count (PMNL), histological lung injury score and plasma thiobarbituric
      acid reactive substances (TBARS) level. RESULTS: PMNL count and MPO activity in
      the lung tissue, and plasma TBARS level were higher in the IR group compared with
      other groups while there were no differences between the sham and the IP and
      between the sham and the IP/IR groups. Histological lung injury score was higher
      in the IR group than in the IP/IR and sham groups. The plasma TBARS level in the
      IP group was significantly lower than in the IP/IR group. CONCLUSION: IP
      pretreatment reduces lipid peroxidation and lung injury caused by lower limb IR.

PMID- 16430535
TI  - The effects of experimental venous carbon dioxide embolization on hemodynamic and
      respiratory variables.
AB  - BACKGROUND: Laparoscopic liver resection is a relatively new surgical procedure.
      Carbon dioxide (CO2) pneumoperitoneum and laparoscopic liver dissection are
      recognized as risk factors for CO2 embolism to the pulmonary circulation. The
      embolization can be difficult to detect and can theoretically increase peri
      operative morbidity. The aim of this study was to evaluate the cardiopulmonary
      effects in a pig model during a time period of 4 h after an experimental CO2
      embolization. METHODS: Eleven piglets were anesthesized. Nine were embolized with
      a single intravenous injection of 0.4 ml/kg CO2 and two served as controls.
      Respiratory and cardiovascular variables, including pulmonary artery pressure and
      cardiac output, were monitored for 4 h after embolization, and arterial blood
      gases were monitored on-line. RESULTS: The embolized piglets had an increase in
      ventilatory dead space, pulmonary vascular resistance and pulmonary artery
      pressure and a decrease in cardiac output that lasted throughout the 4-h
      observation time. The mean arterial pressure and heart rate were unchanged. An
      early sign of embolization was a rapid fall in end-tidal CO2 and P(a)O2 and a
      rise in P(a)CO2. CONCLUSION: Negative changes in cardiopulmonary physiology
      persisted for at least 4 h after a single intravenous CO2 injection, in spite of
      this gas being highly soluble in blood. This is a more prolonged influence of CO2
      embolization than previously described. Extensive monitoring for early detection
      of an embolization may be recommended to limit morbidity in patients undergoing
      laparoscopic liver surgery.

PMID- 16430536
TI  - Gene expression of pulmonary cytokines after sevoflurane or thiopentone
      anaesthesia in pigs.
AB  - BACKGROUND: Volatile anaesthetics have diverse inflammatory effects on the lungs.
      They increase gene expression of some pro-inflammatory cytokines in alveolar
      macrophages whereas in alveolar type II cells they seem to decrease secretion and
      gene expression of pro-inflammatory cytokines. We have previously detected
      increased leukotriene C4, nitrate and nitrite concentrations in bronchoalveolar
      lavage fluid after sevoflurane anaesthesia. In the current study, we measured
      gene expression of inflammatory cytokines in the lung tissue and plasma
      concentrations of cytokines in pigs after thiopentone or sevoflurane anaesthesia.
      METHODS: Sixteen pigs were randomly selected to receive either a continuous
      thiopentone infusion (control group, n = 8) or sevoflurane (n = 8) at 4.0%
      inspiratory concentration (1.5 MAC) in air for 6 h. Tissue samples were collected
      at the end of the study for measurement of gene expression of inflammatory
      cytokines. Blood samples were collected during anaesthesia for measurement of
      plasma cytokine concentrations. RESULTS: Compared with thiopentone anaesthesia,
      lower gene expression of tumour necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta) in lung tissue was observed after sevoflurane anaesthesia. Of
      measured cytokines IL-1beta, TNF-alpha, IL-6, IL-8 and IL-10 only plasma
      concentrations of IL-6 could be measured during the study without a difference
      between the groups. CONCLUSION: Lower gene expression of TNF-alpha and IL-1beta
      was found in the intact porcine lung tissue after sevoflurane anaesthesia
      compared with thiopentone anaesthesia. Clinical significance of this finding is
      unknown.

PMID- 16430537
TI  - Effects of aprotinin on plasma coagulation kinetics determined by
      thrombelastography: role of Factor XI.
AB  - BACKGROUND: Aprotinin is commonly administered in settings involving
      cardiopulmonary bypass and liver transplantation to decrease peri-operative
      bleeding. Thrombelastography has been utilized to monitor coagulation in these
      settings, and aprotinin delays clot initiation, presumably by inhibiting
      kallikrein; however, aprotinin also inhibits Factor XI (FXI), a contact system
      protein. Thus, it was hypothesized that celite-activated thrombelastography
      coagulation kin-etics would be decreased via aprotinin-mediated FXI inhibition.
      METHODS: Citrated normal plasma and prekallikrein-deficient (<1% normal activity)
      plasma were exposed to 0, 200, 400 or 800 kallikrein inhibitory units (KIU)/ml (n
      = 6 per condition). Samples were recalcified and celite-activated in a
      thrombelastograph, with clot initiation (R, s) determined. To confirm contact
      system specificity, additional prekallikrein-deficient samples with 0 or 800
      KIU/ml aprotinin were activated with tissue factor (n = 4 per condition).
      RESULTS: Exposure of celite-activated, normal plasma to aprotinin 0, 200, 400 or
      800 KIU/ml resulted in R values of 167 +/- 14, 253 +/- 10, 293 +/- 22 and 349 +/-
      21 s, respectively, which were significantly different from one another (P <
      0.05). Exposure of celite-activated, prekallikrein-deficient plasma to aprotinin
      0, 200, 400 or 800 KIU/ml resulted in R values of 366 +/- 15, 630 +/- 64, 698 +/-
      46 and 850 +/- 47 s, respectively, which were significantly different from one
      another (P < 0.05). There were no significant differences in R values between
      tissue factor-activated, prekallikrein-deficient plasma samples with 0 or 800
      KIU/ml aprotinin. CONCLUSIONS: These data support a role for the inhibition of
      FXI as the mechanism for aprotinin-mediated delayed contact system clot
      initiation determined by thrombelastography.

PMID- 16430538
TI  - Organ system dysfunction following open cholecystectomy for acute acalculous
      cholecystitis in critically ill patients.
AB  - BACKGROUND: Acute acalculous cholecystitis (AAC) refers to cholecystitis without
      gallstones and is a serious complication of critical illness. We describe the
      time course of organ system dysfunction associated with cholecystectomy in
      critically ill patients with AAC. METHODS: The data of all intensive care unit
      (ICU) patients who had operatively confirmed AAC during their ICU stay between
      2003 and 2004 were analyzed. Patients who also had other intra-abdominal
      pathologies were excluded. The Sequential Organ Failure Assessment (SOFA) scores
      were recorded 3 days before, on the day of operation and on the first, second,
      third and seventh post-operative day after cholecystectomy. The impact of open
      cholecystectomy on organ dysfunction was evaluated on the basis of the change in
      the total and individual organ SOFA scores. RESULTS: Twenty-four patients
      underwent open cholecystectomy for AAC with no other intra-abdominal pathology.
      Sepsis was the most common admission diagnosis, followed by cardiovascular
      surgery. The mean (standard deviation, SD) Acute Physiology and Chronic Health
      Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS) II and SOFA
      scores on admission were 24.7 (5.8), 44.3 (12.3) and 9.4 (3.2), respectively. The
      median (25th, 75th percentiles) total SOFA score 3 days before cholecystectomy
      was 7.5 (1.3, 8.0), which increased to 10.5 (8.3, 13.0) (P < 0.0001) by the day
      of cholecystectomy, indicating developing multiorgan dysfunction. After the
      operation, the score decreased to 5.5 (3.3, 10.8) (P = 0.004) by the seventh post
      operative day. The change was most obvious in cardiovascular and respiratory SOFA
      scores. CONCLUSIONS: AAC is associated with multiorgan dysfunction in critically
      ill patients. Open cholecystectomy seems to alter the course of multiorgan
      dysfunction in these patients.

PMID- 16430539
TI  - Clonidine premedication effects on inhaled induction with sevoflurane in adults:
      a prospective, double-blind, randomized study.
AB  - BACKGROUND: The purpose of this study was to evaluate whether oral clonidine
      premedication becomes an alternative to N2O in terms of shortening the induction
      time and attenuation of the adrenergic response to tracheal intubation during
      inhalation induction with sevoflurane, and to evaluate the quality of anesthetic
      induction according to the patient's satisfaction. METHODS: We studied 84 female
      patients who were randomly allocated into four study groups: Groups I and II
      received a placebo orally, and Groups III and IV received clonidine at 150 and
      300 microg, respectively, 90 min before induction of anaesthesia. Patients were
      anesthetized using a triple-deep-breath technique with 5% sevoflurane in Groups
      I, III and IV, and with 60% N2O-5% sevoflurane in group II. RESULTS: Induction
      time was significantly longer (P < 0.05) in Group I. Increases in mean blood
      pressure and heart rate after tracheal intubation were significantly suppressed
      in Groups III and IV but not in Group II compared with Group I. Comfort and
      impression of anesthesia was better in Groups III and IV than in Groups I and II.
      CONCLUSION: In volatile anesthetic induction, pre-anesthetic clonidine may become
      an alternative to N2O and may provide more comfort than with N2O.

PMID- 16430540
TI  - The electrocardiographic and hemodynamic effect of metohexital and propofol with
      and without esmolol.
AB  - BACKGROUND: Metohexital and propofol are short-acting induction agents, which
      have a tendency to prolong the QTc interval of the ECG. We studied whether this
      increase could be prevented by combining a beta-blocking agent, esmolol, with
      these drugs. Simultaneously, we studied the hemodynamic effects of these
      combinations. METHODS: In a randomized, double-blind study, 80 ASA I-II young
      adults were premedicated with oxycodone and atropin and allocated to one of four
      groups: propofol (P), propofol + esmolol (P + E), metohexital (E) or metohexital
      + esmolol (M + E). The doses were 2 mg/kg propofol/metohexital and 1 mg/kg
      esmolol. Alfentanil 15 microg/kg was used in all groups. The hemodynamic
      parameters were measured non-invasively and the electrocardiographic parameters
      using the signal processing method. RESULT: The highest QTc values, which often
      exceeded the normal upper limit of 440 ms, were recorded at the baseline or
      immediately after the administration of the induction drugs. The intervals were
      significantly shorter if esmolol was co-administered with either propofol or
      metohexital. The heart rate increased in the group M and decreased in the group P
      + E but remained unchanged in the groups P and M + E. Systolic and diastolic
      arterial pressures decreased during the study in all groups, most prominently in
      group P + E. CONCLUSIONS: During the anesthesia induction, the QTc interval was
      significantly shorter when esmolol was co-administered with either propofol or
      metohexital. The hemodynamic responses were properly controlled with the
      combination of metohexital and esmolol as well as with propofol alone, but the
      combination of propofol and esmolol tended to cause hemodynamic depression.

PMID- 16430541
TI  - Suppression of the human spinal H-reflex by propofol: a quantitative analysis.
AB  - BACKGROUND: The spinal cord is an important site of anaesthetic action because it
      mediates surgical immobility. During anaesthesia with volatile anaesthetics, it
      has been shown that the suppression of the spinal H-reflex correlates with
      surgical immobility. To evaluate whether the H-reflex could also be a possible
      candidate for monitoring immobility during propofol anaesthesia, this study
      assessed the concentration-dependent suppression of the H-reflex by propofol. To
      discriminate different effect sites, the individual concentration response-curves
      and the t(1/2ke0) of the H-reflex have been compared with those of two EEG
      parameters. METHODS: In 18 patients, anaesthesia was induced and maintained with
      propofol infused using a target-controlled infusion pump at stepwise increasing
      and decreasing plasma concentrations between 0.5 and 4.5 mg/l. The H-reflex of
      the soleus muscle was recorded at a frequency of 0.1 Hz. Calculated propofol
      concentrations and H-reflex amplitude were analysed in terms of a pharmacokinetic
      pharmacodynamic (PKPD) model with a sigmoid concentration-response function.
      RESULTS: For slowly increasing propofol concentrations, computer fits of the PKPD
      model for H-reflex suppression by propofol yielded the following median
      parameters: EC50 1.1 (0.8-1.7) mg/l, slope parameter 2.4 (2.0-3.7), and a
      t(1/2ke0) of 6.7 (2.8-7.5, 25-75% quantiles) min. For the bispectral index, the
      t(1/2ke0) was 2.2 (1.8-3.1) min and for the spectral edge frequency at the 95th
      percentile of the power spectrum 2.8 (1.9-3.2) min. CONCLUSIONS: Propofol, unlike
      sevoflurane, suppresses the spinal H-reflex at concentrations far lower than the
      C50 skin incision. The differences in t(1/2ke0)-values indicate the presence of
      different effect compartments for effects on the H-reflex and the EEG.

PMID- 16430542
TI  - Comparison of tracheal tube cuff diameters with internal transverse diameters of
      the trachea in children.
AB  - BACKGROUND: In this study, we evaluated the ratio of the cuff diameters of the
      Microcuff paediatric tracheal tube (Microcuff PET, Weinheim, Germany) to
      fluoroscopically measured internal transverse tracheal diameters in children from
      birth to adolescence. METHODS: With Institutional Ethics Committee approval and
      parental consent, we measured the internal transverse tracheal diameters from
      fluoroscopy images in children undergoing cardiac catheterization requiring
      general anaesthesia with oro-tracheal intubation. Minimal tracheal sealing
      pressures were assessed at standardized respirator settings. Internal transverse
      tracheal diameters were compared with cuff diameters at 20 cmH2O cuff pressure.
      Linear regression analysis was employed to assess the correlation of tracheal
      diameters with age, height and weight, and to assess the correlation of the
      cuff/tracheal diameter ratio with sealing pressures. For all tests, P < 0.05 was
      considered to be statistically significant. RESULTS: One hundred and forty-five
      patients were studied (62 girls; 83 boys). Transverse tracheal diameters
      correlated well with age (r = 0.890; P < 0.0001), height (r = 0.900; P < 0.0001)
      and weight (r = 0.882; P < 0.0001). Tracheal sealing pressures ranged from 4 to
      18 cmH2O. The ratio of the tracheal tube cuff diameter to the internal transverse
      tracheal diameter ranged from 1.06 in tubes with internal diameters of 6.0 and
      4.5 mm to 2.01 in a tube with an internal diameter of 3.5 mm (median, 1.43), and
      did not correlate with tracheal sealing pressures (r = 0.021, P = 0.7999).
      CONCLUSIONS: The residual diameters of the Microcuff paediatric tracheal tube
      cuffs were sufficient to cover the measured internal transverse tracheal
      diameters of children from birth to adolescence. This allowed the internal
      tracheal mucosal surface to be draped and the trachea to be sealed at very low
      cuff pressures.

PMID- 16430543
TI  - Factors associated with anaesthesia-related maternal mortality in a tertiary
      hospital in Nigeria.
AB  - BACKGROUND: Maternal mortality related to anaesthesia is low compared with that
      resulting from obstetric factors in developed countries. The role of anaesthesia
      in maternal mortality in developing countries is obscure. The purposes of this
      study were to determine the incidence of maternal mortality related to
      anaesthesia, to analyse the causes and to suggest measures to improve anaesthetic
      safety for parturients. METHODS: The hospital surgical registry was reviewed from
      1 January 1991 to 31 December 2000 to identify patients who had undergone
      surgical procedures in pregnancy or puerperium. Data were obtained from the
      surgical registry in the Labour and Delivery Suite, Intensive Care Unit records
      and maternal mortality database to determine the demographic characteristics and
      anaesthetic technique. Maternal mortality after surgical procedures was further
      scrutinized to evaluate the anaesthetic care and the contribution of anaesthesia
      to mortality. RESULTS: A total of 12,394 deliveries occurred in the hospital
      during the period under review. Caesarean section accounted for 2323 deliveries
      (18.7%). Eighty-four maternal mortalities were recorded, with a maternal
      mortality rate of 678 per 100,000 deliveries. Infection, haemorrhage, pre
      eclampsia/eclampsia and anaesthesia were the leading causes of maternal
      mortality. Anaesthesia was the sole cause of six maternal deaths. The patients
      received general anaesthesia for the surgical procedure. CONCLUSION: Difficult
      airway management during general anaesthesia, inadequate supervision of trainee
      anaesthetists and a lack of appropriate monitors were the major anaesthetic
      reasons for maternal mortality. Recommendations have been made to ensure that
      parturients and the unborn child receive the best anaesthetic care attainable in
      the hospital.

PMID- 16430544
TI  - Changes in magnesium concentration in the serum and cerebrospinal fluid of
      neuropathic rats.
AB  - BACKGROUND: Central sensitization of neuropathic pain is associated with an
      influx of extracellular calcium via the opening of N-methyl-D-aspartate (NMDA)
      receptor-gated ion channels, which are usually blocked by magnesium plugs. As
      magnesium-deficient rats develop a mechanical hyperalgesia and intrathecal or
      intraperitoneal magnesium suppresses neuropathic pain, the magnesium
      concentrations in serum and cerebrospinal fluid may be altered in neuropathic
      pain. We therefore compared the magnesium concentrations in serum and
      cerebrospinal fluid of neuropathic rats with those in injured rats without
      symptoms of neuropathic pain and normal rats. METHODS: Mechanical allodynia was
      induced in male Sprague-Dawley rats by tight ligature of the left lumbar fifth
      and sixth spinal nerves. The threshold of paw withdrawal was evaluated by the up
      down method using withdrawal response to stimulus with a von Frey filament on the
      third, seventh and 14th days. Rats with a threshold of less than 4 g were
      selected as the symptomatic group and compared with an asymptomatic group, an
      unoperated control group and a sham-operated group. On the 16th day, the Mg2+
      concentrations in serum and cerebrospinal fluid were measured. RESULTS: The
      magnesium concentrations in the serum and cerebrospinal fluid of symptomatic
      neuropathic rats did not differ from those in the injured rats without symptoms
      of neuropathic pain, sham-operated rats and normal rats. CONCLUSION: Our results
      suggest that physiologic homeostasis is maintained by active transport through
      the blood-brain barrier despite the activation of NMDA receptor-gated ion
      channels. However, rats with neuropathic pain may be in a magnesium-deficient
      condition at the effector site, such that magnesium treatment can decrease
      neuropathic pain.

PMID- 16430545
TI  - Isobaric bupivacaine via spinal catheter for hip replacement surgery: ED50 and
      ED95 dose determination.
AB  - BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows
      incremental dosing of the local anaesthetic and, consequently, less haemodynamic
      change. However, little is known about the required doses. Therefore, we designed
      a study to assess the local anaesthetic doses of isobaric bupivacaine which were
      effective in 50% (ED50) and 95% (ED95) of patients undergoing hip replacement
      surgery. METHODS: Forty-eight patients undergoing hip replacement surgery were
      randomly allocated to one of six possible groups of eight patients to receive 6,
      7, 8, 9, 10 or 12 mg of isobaric bupivacaine in a double-blind manner. The ED50
      and ED95 values were calculated by a logistic regression model. The position of
      the spinal catheter tip was confirmed by X-rays. RESULTS: The ED50 and ED95
      values were 7.1 mg (95% confidence interval, 6.0-8.4) and 12.3 mg (95% confidence
      interval, 8.9-15.7), respectively. The location of the tip of the intrathecal
      catheter had no effect on local anaesthetic requirements. Eight patients required
      ephedrine after anaesthesia induction and a further 11 patients required
      ephedrine for correction of hypotension during surgery. CONCLUSION: The observed
      ED50 and ED95 values may guide us to use small doses of isobaric bupivacaine for
      hip replacement surgery. Hypotension is still possible even if low doses of
      isobaric bupivacaine are used.

PMID- 16430547
TI  - Analgesic effects of intrathecally administered celecoxib, a cyclooxygenase-2
      inhibitor, in the tail flick test and the formalin test in rats.
AB  - BACKGROUND: The analgesic effects of celecoxib, a cyclooxygenase-2 (COX-2)
      inhibitor, on formalin-induced pain are still controversial. The purpose of this
      study was to examine the analgesic effects of intrathecally administered
      celecoxib on inflammatory induced pain, thermal-induced pain and hemodynamics.
      METHODS: Male Sprague-Dawley rats with lumbar intrathecal catheters were tested
      via their tail withdrawal response to thermal stimulation (tail flick test) and
      via their paw flinching and shaking response to subcutaneous formalin injection
      into the hind paw (formalin test) after intrathecal administration of celecoxib.
      The blood pressure, pulse rate and behavioral side-effects were also examined.
      RESULTS: Even the maximum available dose of celecoxib (200 microg/20 microl) had
      little effect in the tail flick test. In the formalin test, celecoxib induced a
      dose-dependent decrease in the flinch response in both phases 1 and 2. The 50%
      effective doses were 0.025 microg (95% confidence interval, 0.007-0.082 microg)
      in phase 1, 0.026 microg (0.010-0.045 microg) in phase 2a and 0.001 microg
      (0.00009-0.010 microg) in phase 2b. With the doses used in this study, the blood
      pressure and pulse rate did not change and no motor disturbance or behavioral
      side-effects were observed. CONCLUSION: Intrathecal administration of celecoxib
      decreased inflammatory acute and facilitated pain without any hemodynamic or
      behavioral side-effects, but had no effect on acute thermal pain.

PMID- 16430546
TI  - Effect of low-dose dexmedetomidine or clonidine on the characteristics of
      bupivacaine spinal block.
AB  - BACKGROUND: The purpose of this study was to compare the onset and duration of
      sensory and motor block, as well as the hemodynamic changes and level of
      sedation, following intrathecal bupivacaine supplemented with either
      dexmedetomidine or clonidine. METHODS: In a prospective, double-blind study, 60
      patients undergoing transurethral resection of prostate or bladder tumor under
      spinal anesthesia were randomly allocated to one of three groups. Group B
      received 12 mg of hyperbaric bupivacaine, group D received 12 mg of bupivacaine
      supplemented with 3 microg of dexmedetomidine and group C received 12 mg of
      bupivacaine supplemented with 30 microg of clonidine. The onset times to reach
      peak sensory and motor levels, and the sensory and motor regression times, were
      recorded. Hemodynamic changes and the level of sedation were also recorded.
      RESULTS: Patients in groups D and C had a significantly shorter onset time of
      motor block and significantly longer sensory and motor regression times than
      patients in group B. The mean time of sensory regression to the S1 segment was
      303 +/- 75 min in group D, 272 +/- 38 min in group C and 190 +/- 48 min in group
      B (B vs. D and B vs. C, P < 0.001). The regression of motor block to Bromage 0
      was 250 +/- 76 min in group D, 216 +/- 35 min in group C and 163 +/- 47 min in
      group B (B vs. D and B vs. C, P < 0.001). The onset and regression times were not
      significantly different between groups D and C. The mean arterial pressure, heart
      rate and level of sedation were similar in the three groups intra-operatively and
      post-operatively. CONCLUSIONS: Dexmedetomidine (3 microg) or clonidine (30
      microg), when added to intrathecal bupivacaine, produces a similar prolongation
      in the duration of the motor and sensory block with preserved hemodynamic
      stability and lack of sedation.

PMID- 16430548
TI  - Epidural morphine analgesia compared with intravenous morphine for oral cancer
      surgery with pectoralis major myocutaneous flap reconstruction.
AB  - BACKGROUND: Oral cancer surgery with reconstruction is a complex operative
      procedure with morbidities such as respiratory complications and post-operative
      pain. These morbidities may be reduced with appropriate operative and post
      operative pain management. Epidural analgesia provides better pain control than
      intravenous opioids after major thoraco-abdominal surgical procedures. We planned
      to undertake a prospective study to compare the efficacy and side-effects of
      epidural morphine analgesia vs. intravenous morphine in patients undergoing oral
      cancer surgery with pectoralis major myocutaneous flap reconstruction. METHODS:
      Sixty patients undergoing a major surgical procedure for oral cancer with
      pectoralis major myocutaneous flap reconstruction were prospectively randomized
      to receive either epidural morphine or intravenous morphine in the post-operative
      period. The intensity of pain was assessed daily using a 100-mm visual analogue
      scale. The post-operative side-effects, time to ambulation, time to tolerate
      first nasogastric feed, total length of hospital stay and global satisfaction
      score were recorded. RESULTS: The epidural morphine group had statistically
      significant lower pain scores at the three evaluation times through the post
      operative 48 h (P < 0.05). However, the mean visual analogue scores were always
      below 35 in the intravenous morphine group. Patients in the epidural morphine
      group ambulated and accepted nasogastric feed significantly earlier than those in
      the intravenous morphine group. The incidence of nausea/vomiting or pruritus, the
      length of hospital stay and the global satisfaction score were not statistically
      different between the groups. CONCLUSION: This study illustrates that epidural
      morphine offers better pain control than intravenous morphine after oral cancer
      surgery with pectoralis major myocutaneous flap reconstruction. Nevertheless,
      both methods appear to provide very good pain relief, and perhaps the extra risks
      inherent to epidural catheter insertion are not outweighed by the benefits in
      this type of surgery.

PMID- 16430549
TI  - Ondansetron and tropisetron do not prevent intraspinal morphine- and fentanyl
      induced pruritus in elective cesarean delivery.
AB  - BACKGROUND: Although intraspinal morphine has been shown to be effective in
      providing analgesia after cesarean delivery, pruritus as a side-effect remains a
      common cause of dissatisfaction. The role of ondansetron has been studied in
      preventing pruritus but the results have been contradictory. METHODS: We
      randomized 98 parturients undergoing elective cesarean section using combined
      spinal-epidural anesthesia into a double-blinded trial to receive tropisetron 5
      mg (T group) or ondansetron 8 mg (O group) or placebo (NaCl group) after
      delivery, when intrathecal morphine 160 microg and fentanyl 15 microg were used
      for post-operative pain control. The patients additionally received ketoprofen
      300 mg per day. Post-operative itching, nausea and vomiting, sedation and need
      for rescue analgesics were registered every 3 h up to 24 h, and all patients were
      interviewed on the first post-operative day. RESULTS: Seventy-six percent of the
      parturients in the placebo group, 87% in the ondansetron, and 79% in the
      tropisetron group had itching. The incidence of post-operative nausea and
      vomiting was 21%, 20% and 11% of the patients in the placebo, ondansetron and
      tropisetron groups, respectively. Medication for pruritus was needed by 31%, 23%
      and 39% of the patients in the placebo, ondansetron and tropisetron groups,
      respectively. In the post-operative questionnaire, the patients reported less
      post-operative nausea in the tropisetron group than in the placebo group (P <
      0.01). CONCLUSION: Neither ondansetron nor tropisetron prevent itching caused by
      intrathecal morphine with fentanyl. However, tropisetron reduced post-operative
      nausea.

PMID- 16430550
TI  - Anaphylactic reaction to patent blue V after sentinel lymph node biopsy.
AB  - BACKGROUND: We report a documented grade III IgE-mediated hypersensitivity
      reaction associated with the use of 2.5% patent blue V dye for sentinel lymph
      node biopsy during breast cancer surgery. METHODS: Immediately after the
      reaction, when hemodynamic stability was obtained, plasma histamine was measured
      whereas serum tryptase was not. Six weeks later, with the patient's consent,
      cutaneous tests to patent blue V dye, methylene blue dye, latex and all drugs
      used during surgery were performed according to standardized procedures. RESULTS
      AND CONCLUSION: Clinical symptoms, biological assessment results and cutaneous
      tests positivity confirmed the onset of an anaphylactic reaction due to patent
      blue V. Of interest, the positivity of the cutaneous tests observed with patent
      blue V was not found with methylene blue which might be proposed for further
      investigations in our patient. This case report confirms the need for systematic
      allergological investigation of all drugs and substances administered during the
      peri-operative period in case of an immediate hypersensitivity reaction occurring
      during anesthesia.

PMID- 16430551
TI  - Pulmonary embolism caused by polymethylmethacrylate during percutaneous
      vertebroplasty in orthopaedic surgery.
AB  - Vertebroplasty consists of percutaneous injection of acrylic cement-
      polymethylmethacrylate (PMMA)--into a partially collapsed vertebral body in order
      to obtain pain relief and augment mechanical stability of the vertebral body.
      Although vertebroplasty is an efficient treatment it is not free of
      complications. Our present case report describes a woman with pulmonary
      polymethylmethacrylate embolism during percutaneous vertebroplasty who presented
      with hypotension, arrhythmia and hypocapnia.

PMID- 16430552
TI  - Cerebral microdialysis and P(ti)O2 for neuro-monitoring before decompressive
      craniectomy.
AB  - We report the case of a young patient with post-traumatic, intractable,
      intracranial hypertension leading to craniectomy. This intracranial hypertension
      was preceded by focal signs of ischemia diagnosed through P(ti)O2 monitoring and
      cerebral microdialysis, and occurred a few hours prior to a decrease in cerebral
      perfusion pressure below 60 mmHg. The neurological outcome was satisfactory with
      a Glasgow Outcome Scale of 4 at 3 months. We discuss the potential interest of
      such neuro-monitoring to determine the optimal time for performing a craniectomy.

PMID- 16430553
TI  - Prevention of acute renal failure--first do no harm!

PMID- 16430555
TI  - Understanding spinal anesthesia.

PMID- 16430556
TI  - Accidental disconnection of the epidural catheter: to reconnect or replace?

PMID- 16430557
TI  - Education, in addition to a thin material, encourages anaesthetists to wear
      gloves.

PMID- 16430558
TI  - Glycine is toxic.

PMID- 16430560
TI  - Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob.

PMID- 16430561
TI  - Minimum local anaesthetic dose (MLAD) of intrathecal levobupivacaine and
      ropivacaine for Caesarean section.
AB  - We determined the minimum local anaesthetic dose (MLAD) of spinal levobupivacaine
      and ropivacaine for Caesarean section. Ninety women were randomly allocated to
      two groups and received 3 ml of study solution by a combined spinal/epidural
      technique. The initial dose was 12 mg for levobupivacaine and 17 mg for
      ropivacaine groups. To be considered effective, a test solution had to achieve a
      visual analogue pain score (VAPS) of 30 mm or less at skin incision, uterine
      incision, birth, peritoneal closure, and at the end of surgery. Effective or
      ineffective responses determined, respectively, a 0.3 mg decrease or increase of
      the same drug for the next patient in the same group, using up-down sequential
      allocation. The MLAD of levobupivacaine was 10.58 mg (CI 95%: 10.08-11.09) and
      the MLAD of ropivacaine 14.22 mg (CI 95%: 13.67-14.77), using the Dixon and
      Massey formula. The potency ratio between spinal levobupivacaine and spinal
      ropivacaine was 1.34.

PMID- 16430562
TI  - Postoperative pain, nausea and vomiting following paediatric day-case
      tonsillectomy.
AB  - More than 30% of all surgical activity for children in England and Wales is
      accounted for by routine ENT operations. There is known to be a high incidence of
      postoperative pain, nausea and vomiting following paediatric tonsillectomy with
      or without adenoidectomy. This prospective study examined the incidence of these
      complications in 100 children admitted for routine, elective day-case
      tonsillectomy, with or without adenoidectomy. The children were anaesthetised in
      accordance with our standard paediatric day-case protocol. The incidence of
      vomiting on the day of surgery was significantly less in the group anaesthetised
      in accordance with the protocol, compared to those in previously published
      studies. Postoperative pain was well controlled, with 88% of the children having
      minimal pain on the day of surgery, and reporting a pain score of 0-2. Modifying
      the anaesthetic care to a protocol designed to reduce postoperative pain, nausea
      and vomiting achieved measurable improvements in the recovery of this group
      following surgery. It has enabled us to evolve from a 100% inpatient stay for
      these operations to 98% day-case discharge rate, with minimal post anaesthetic or
      surgical morbidity. We describe the protocol and discuss the implications of
      implementing such a protocol for children undergoing these common operations.

PMID- 16430564
TI  - Pre-operative detection of valvular heart disease by anaesthetists.
AB  - We prospectively estimated the prevalence of heart murmurs in 2522 consecutive
      adult non-cardiac surgery patients during pre-operative evaluation. Factors that
      contribute to the detection of a heart murmur were identified, and
      echocardiography was used to evaluate to what extent a murmur reflected presence
      of valvular heart disease. A cardiac murmur was detected in 106 patients
      (prevalence 4.2%, 95% CI: 3.5-5.1%). Multivariable logistic regression analyses
      showed that age and general physical impression were independently associated
      with detecting a murmur (p-values < 0.01). In 83 (79%) of the patients with a
      murmur, an echocardiographic diagnosis was available: 39% had aortic valve
      abnormalities, 24% had mitral valve regurgitation, 7% had other valvular heart
      disease and 30% did not have any abnormality. Thus, 58 of the 83 patients had
      valvular heart disease (positive predictive value using routine cardiac
      auscultation for diagnosing VHD: 70%, 95% CI: 59-79%). Murmurs in patients
      younger than 40 years never reflected valvular heart disease. Pre-operative
      cardiac auscultation seems only reasonable in patients aged 40 years or older.
      Subsequent echocardiography in these selected patients is necessary.

PMID- 16430563
TI  - Study of a combined percutaneous local anaesthetic and the TDS system for
      venepuncture.
AB  - Transdermal Delivery System (TDS) is a liquid formulation which can be applied to
      the skin via a metered pump spray to deliver drug across skin. This placebo
      controlled, double blind trial compared anaesthetic properties of two TDS systems
      (TDS alpha and TDS beta) with placebo. The active and placebo treatments were
      applied to the dorsum of the hands, bilaterally and simultaneously for 5 min on
      100 healthy volunteers. Following cannulation, pain perception was measured using
      the verbal rating score (VRS) and visual analogue score (VAS). Lidocaine plasma
      levels were assessed at 0 and 2 h. The VRS and VAS results show that TDS beta
      significantly decreased pain score compared to placebo (p < 0.02). Blood
      lidocaine at 2 h post application was also higher for TDS beta than for TDS
      alpha, suggesting that a 5 min application of TDS beta was effective in
      delivering local anaesthetic and accelerating the onset of skin anaesthesia prior
      to venous cannulation in adults.

PMID- 16430565
TI  - The effect of gel lubrication on cuff leakage of double lumen tubes during
      thoracic surgery.
AB  - High-volume, low-pressure tracheal cuffs of disposable double lumen tubes may
      offer limited protection to the dependent lung if fluid leaks through folds in
      the inflated cuffs. This study was undertaken to determine the incidence of fluid
      leakage past the tracheal cuff and whether gel lubrication reduces the incidence.
      Fifty-five patients were randomly assigned to receive a double lumen tube with or
      without gel lubrication. The dependent lung was intubated. With the patient in
      the lateral position, methylthionium chloride was administered above the tracheal
      cuff via a pre-attached catheter. Fibreoptic bronchoscopy was performed to
      determine if dye had passed the tracheal cuff. Three patients were excluded. Dye
      leakage was seen in 12/27 and 3/25 patients in the unlubricated and lubricated
      group, respectively (p = 0.014). Gel lubrication significantly reduces fluid
      leakage past the tracheal cuff of a double lumen tube and should be considered
      for all thoracic surgical patients requiring one-lung ventilation.

PMID- 16430566
TI  - Haemodynamic effects of the prone position: a comparison of propofol total
      intravenous and inhalation anaesthesia.
AB  - The haemodynamic changes of the prone position were investigated in 40 ASA I-II
      patients undergoing lumbar spine surgery. Patients were randomly assigned,
      following propofol intravenous induction, to receive maintenance of anaesthesia
      using either isoflurane 1-1.2% in air or target controlled propofol 3 microg.ml(
      1) infusion. Measurements of non-invasive blood pressure, heart rate and cardiac
      output were made in the supine position. The patient was then turned prone onto a
      Montreal pattern mattress and measurements repeated. Cardiac output measurements
      were made using a non-invasive cardiac output monitor. We found a significant
      reduction in cardiac index in both groups and a significantly greater change with
      propofol compared to isoflurane on turning supine to prone (CI change 0.4 vs 0.7
      l.min(-1).m(-2) p = 0.001 and SVRI change 89 vs 177 dyne.s(-1).cm(-5), p =
      0.041). We conclude that turning healthy patients prone produces a clinically
      significant reduction in cardiac output, the change being greater during
      maintenance of anaesthesia using propofol compared to isoflurane.

PMID- 16430567
TI  - Learnability and discriminability of melodic medical equipment alarms.
AB  - Melodic alarms proposed in the IEC 60601-1-8 standard for medical electrical
      equipment were tested for learnability and discriminability. Thirty-three non
      anaesthetist participants learned the alarms over two sessions of practice, with
      or without mnemonics suggested in the standard. Fewer than 30% of participants
      could identify the alarms with 100% accuracy at the end of practice. Confusions
      persisted between pairs of alarms, especially if mnemonics were used during
      learning (p = 0.011). Participants responded faster (p < 0.00001) and more
      accurately (p = 0.002) to medium priority alarms than to high priority alarms,
      even though they rated the high priority alarms as sounding more urgent (p <
      0.00001). Participants with at least 1 year of formal musical training identified
      the alarms more accurately (p = 0.0002) than musically untrained participants,
      and found the task easier overall (p < 0.00001). More intensive studies of the
      IEC 60601-1-8 alarms are needed for their effectiveness to be determined.

PMID- 16430568
TI  - Visualisation of needle position using ultrasonography.
AB  - Anaesthetists and intensivists spend a considerable proportion of their working
      time inserting needles and catheters into patients. In order to access deeper
      structures like central veins and nerves, they have traditionally relied on
      surface markings to guide the needle into the correct position. However, patients
      may present challenges due to anatomical abnormalities and size. Irrespective of
      the skill of the operator, there is the ever-present risk of needle misplacement
      with the potential of damage to structures like arteries, nerve bundles and
      pleura. Repeated attempts, even if ultimately successful, cause patient suffering
      and probably increase the risk of infection and other long term complications.
      Portable and affordable, high-resolution ultrasound scanners, has accelerated the
      interest in the use of ultrasound guidance for interventional procedures.
      Ultrasound guidance offers several advantages including a greater likelihood of
      success, fewer complications and less time spent on the procedure. Even if the
      target structure is identified correctly there is still the challenge to place
      the needle or other devices in the optimum site. The smaller and deeper the
      target, the greater the challenge and potential usefulness of ultrasound
      guidance. As a result of limited training in the use of ultrasound we believe
      that many clinicians fail to use it to its full potential. A lack of
      understanding, with regard to imaging the location of the needle tip remains a
      major obstacle. Needle visualisation and related topics form the basis for this
      review.

PMID- 16430569
TI  - Liver enzyme induction and inhibition: implications for anaesthesia.
AB  - Recent breakthroughs in molecular biology have enabled a reclassification of drug
      metabolising enzymes based on their amino acid sequence. This has led to a better
      understanding of drug metabolism and drug interactions. The majority of these
      drug metabolising enzymes may be either induced or inhibited by drugs or by
      extraneous substances including foodstuffs, cigarette smoke and environmental
      pollutants. Virtually all drugs used in anaesthesia are metabolised by either
      hepatic phase 1 or phase II enzymes. This review considers the classification of
      drug metabolising enzymes, explains the mechanisms of enzyme induction and
      inhibition, and also considers how the action of drugs commonly used by
      anaesthetists, including opioids and neuromuscular blocking drugs, may be altered
      by this mechanism.

PMID- 16430570
TI  - A comparison of the Soft Seal disposable and the Classic re-usable laryngeal mask
      airway.
AB  - Many new supraglottic airway devices have been recently introduced, their
      development motivated by the need for a single-use equivalent to the original re
      usable laryngeal mask airway. We performed a randomised cross-over study in
      spontaneously breathing patients comparing the re-usable Laryngeal Mask Airway
      Classic (LMA) and the disposable Soft Seal Laryngeal Mask in sizes 3, 4 and 5.
      Sixty patients had an LMA and a disposable laryngeal mask placed in random order.
      The primary outcome was first attempt insertion success rate. Ease of insertion
      was similar in both groups and there was no difference in first attempt success
      rates (96% with LMA and 92% with disposable laryngeal mask). The disposable
      laryngeal mask required significantly less air to inflate the cuff to produce a
      seal (10 [10-25] ml with disposable laryngeal mask and 15 [10-30] ml with
      laryngeal mask) and the cuff pressure produced was significantly lower (35 [20
      80] cmH(2)O with disposable laryngeal mask and 75 [20-120] cmH(2)O with LMA).
      Data are median and range. We conclude that the disposable laryngeal mask is an
      acceptable alternative to the re-usable LMA.

PMID- 16430571
TI  - A comparison of two single dilator percutaneous tracheostomy sets: the Blue Rhino
      and the Ultraperc.
AB  - The single tapered dilator kit is the most commonly used percutaneous
      tracheostomy set in the UK. The Cook Blue Rhino and the Portex Ultraperc were
      compared in the laboratory on mannequin and porcine airway models. The following
      data were collected: the subjective ease of dilating the trachea and inserting
      the tracheostomy tube; the time taken and the anterior-posterior compression
      during dilatation and tube insertion; the incidence and extent of posterior
      tracheal wall damage. During dilatation, the Blue Rhino caused less mean
      percentage anterior-posterior compression (34.8% vs. 51.5%, p = 0.0014). There
      was no difference in subjective ease or time for dilatation in either mannequin
      or porcine airway models. During insertion of the tracheostomy tube, the
      Ultraperc was subjectively easier in the porcine airway model (p = 0.001); had a
      shorter median insertion time in both the mannequin (3 s vs. 7.2 s, p = 0.0006)
      and the porcine airway model (4.3 s vs. 8.5 s, p = 0.0005); the mean percentage
      anterior-posterior compression caused was less in the mannequin (51.5% vs. 76%, p
      = 0.0008). The overall incidence of posterior wall damage was 65% with 25% having
      deep lacerations. There was no difference in the incidence of damage between the
      two sets. The Ultraperc therefore has advantages during tracheostomy tube
      insertion that are statistically and clinically significant. The advantages are
      probably due to the presence of the tracheostomy tube introducer.

PMID- 16430572
TI  - Ruptured splenic artery aneurysm in pregnancy presenting in a manner similar to
      pulmonary embolus.
AB  - We report a patient, 33 weeks pregnant with twins, who sustained a ruptured
      splenic artery aneurysm. This presented with left sided chest pain,
      breathlessness, low oxygen saturations and electrocardiogram (ECG) changes
      supportive of a diagnosis of massive pulmonary embolus. The diagnosis of splenic
      artery rupture was made at emergency Caesarean section performed for fetal
      distress.

PMID- 16430573
TI  - Etomidate--misused or misunderstood?

PMID- 16430574
TI  - Etomidate--misused or misunderstood?

PMID- 16430576
TI  - Failed intubation in obstetric anaesthesia.

PMID- 16430577
TI  - Etomidate and ECT.

PMID- 16430578
TI  - Etomidate and ECT.

PMID- 16430580
TI  - Remifentanil for tracheal intubation.

PMID- 16430581
TI  - Remifentanil for tracheal intubation.

PMID- 16430582
TI  - Remifentanil for tracheal intubation.

PMID- 16430583
TI  - Cardiovascular responses following laryngoscope-assisted fibreoptic orotracheal
      intubation.

PMID- 16430585
TI  - Shearing of a Frova Intubating Introducer by a Bronchocath double lumen tube.

PMID- 16430588
TI  - Use of ProSeal laryngeal mask airway as a dedicated airway for fibreoptic-guided
      tracheal intubation.

PMID- 16430589
TI  - Non-invasive ventilation for acute respiratory failure due to a snakebite.

PMID- 16430590
TI  - Another cause of an obstructed breathing system.

PMID- 16430591
TI  - Temporomandibular joint dislocation after use of a laryngeal mask airway.

PMID- 16430592
TI  - Frozen succinylcholine.

PMID- 16430594
TI  - Crouching gasman; hidden larynx.

PMID- 16430598
TI  - Managed care market share and primary treatment for cancer.
AB  - OBJECTIVE: Increases in the market share of managed care are associated with
      decreases in expenditures in the fee-for-service sector. To understand
      utilization patterns responsible for such savings, we assessed whether increases
      in managed care market share were related to increases in receipt of equally
      effective but less costly primary cancer therapies. DATA SOURCES: Cancer registry
      data linked to Medicare administrative data for a population-based sample of fee
      for-service Medicare beneficiaries 66 years and older who were diagnosed with
      breast or prostate cancer during 1993-1999. STUDY DESIGN: We used fixed-effects
      regression models to assess whether county-level increases in the market share of
      managed care were associated with differences in receipt of cancer therapies that
      are similar in effectiveness but vary in cost. PRINCIPAL FINDINGS: Increases in
      the market share of managed care were not associated with differences in the
      receipt of mastectomy versus breast-conserving surgery with radiation for women
      with early stage breast cancer (p=.47) or with the receipt of conservative
      therapy (versus surgery or radiation therapy) for men with local or regional
      prostate cancer (p=.30). CONCLUSIONS: Increases in the market share of managed
      care do not appear to influence the receipt of equally effective primary
      treatments for cancer in the fee-for-service sector.

PMID- 16430599
TI  - Does wait-list size at registration influence time to surgery? Analysis of a
      population-based cardiac surgery registry.
AB  - OBJECTIVE: To determine whether the probability of undergoing coronary bypass
      surgery within a certain time was related to the number of patients on the wait
      list at registration for the operation in a publicly funded health system.
      METHODS: A prospective cohort study comparing waiting times among patients
      registered on wait lists at the hospitals delivering adult cardiac surgery. For
      each calendar week, the list size, the number of new registrations, and the
      number of direct admissions immediately after angiography characterized the
      demand for surgery. RESULTS: The length of delay in undergoing treatment was
      associated with list size at registration, with shorter times for shorter lists
      (log-rank test 1,198.3, p<.0001). When the list size at registration required
      clearance time over 1 week patients had 42 percent lower odds of undergoing
      surgery compared with lists with clearance time less than 1 week (odds ratio [OR]
      0.58 percent, 95 percent, confidence interval [CI] 0.53-0.63), after adjustment
      for age, sex, comorbidity, period, and hospital. The weekly number of new
      registrations exceeding weekly service capacity had an independent effect toward
      longer service delays when the list size at registration required clearance time
      less than 1 week (OR 0.56 percent, 95 percent CI 0.45-0.71), but not for longer
      lists. Every time the operation was performed for a patient requiring surgery
      without registration on wait lists, the odds of surgery for listed patients were
      reduced by 6 percent (OR 0.94, CI 0.93-0.95). CONCLUSION: For wait-listed
      patients, time to surgery depends on the list size at registration, the number of
      new registrations, as well as on the weekly number of patients who move
      immediately from angiography to coronary bypass surgery without being registered
      on a wait list. Hospital managers may use these findings to improve resource
      planning and to reduce uncertainty when providing advice on expected treatment
      delays.

PMID- 16430600
TI  - A needle in a haystack? Uninsured workers in small businesses that do not offer
      coverage.
AB  - OBJECTIVE: To describe the insurance status of workers at small businesses, and
      to describe the status of uninsured persons by the employment characteristics
      (employment status, firm size, and whether the employer offers insurance) of the
      head of household. DATA SOURCES: Data from the March and February 2001 Current
      Population Survey, and a survey of 2,830 small businesses in San Diego County
      conducted in 2001. STUDY DESIGN: The survey of small businesses was undertaken as
      part of a project testing the response of employers to offers of subsidized
      coverage. Employers were asked whether they offered insurance, and about the
      insurance status of their employees. The merged February-March 2001 CPS was used
      to identify the employment status, firm size, and employer-offering status for
      uninsured persons in the U.S. DATA COLLECTION: Telephone interviews with small
      businesses in San Diego County. PRINCIPAL FINDINGS: Only 21 percent of the
      uninsured in the U.S. are full-time employees (or their dependents) in small
      businesses (<100 employees) that do not offer insurance. The employment status of
      the uninsured is heterogeneous: many work for large employers, small employers
      who do offer insurance, or are self-employed, part-time workers, or have no
      workers in the household. Although there are many small businesses in San Diego
      that do not offer coverage, most of them have very few uninsured workers. Over 50
      percent of businesses that do not offer coverage have either zero or one
      uninsured worker. There are very few small businesses that do not offer coverage
      and that have substantial numbers of uninsured workers. These businesses are not
      quite as rare as a needle in a haystack, but they are very difficult to find.
      CONCLUSIONS: If all small businesses that do not offer insurance now could be
      persuaded to start offering coverage, and if all the full-time workers (and their
      dependents) in those businesses accepted insurance, the number of uninsured would
      decline by 21 percent--a significant decline, but leaving 80 percent of the
      problem untouched. If the prime target for programs of subsidized insurance are
      small businesses that do not offer coverage now and that have substantial numbers
      of uninsured workers, the target is very small.

PMID- 16430601
TI  - A measure of trust in insurers.
AB  - BACKGROUND: Patient-centered assessments are increasingly important. Patients
      repeatedly emphasize the importance of trust in health care institutions and
      personnel. OBJECTIVES: (1) Develop a conceptual framework for trust in health
      care organizations and a comprehensive, reliable measure of trust in health
      insurers. (2) Examine predictors and correlates of trust in insurers. STUDY
      DESIGN: A conceptual framework for trust in health organizations based on theory
      and empirical studies was used to develop items for a structured telephone
      survey, which also included measures of health and utilization, doctor-patient
      trust, and satisfaction with care. Principal components factor analyses
      identified hypothesized domains of trust in health insurers and identified items
      for scales. Internal consistency assessment used Cronbach's alpha. Univariate
      analyses used Pearson's r or Student's t-tests. SAMPLE: Insured residents of
      Southeastern Michigan (n=400). RESULTS: Respondents were diverse in age, gender,
      ethnicity, health, and socioeconomic status. One dominant factor (eigenvalue>10)
      included hypothesized domains: administrative competence, clinical competence,
      advocacy and beneficence, fairness, honesty and openness, and one global item.
      Multidimensional scales were reliable (long version 13 items, alpha=0.95, short:
      9 items, alpha=0.91). Insurer trust correlated strongly with trust in doctors
      (r=0.49 and 0.46) and satisfaction with care (r=0.70 and 0.66), and with an item
      assessing overall worry about health insurance (r=-0.37 and -0.35). Those with
      less trust in their insurer were more likely to say that they would change
      insurance plans (p<.001). CONCLUSIONS: This well-grounded, reliable measure of
      enrollee trust in insurers can be a useful patient-centered assessment tool.

PMID- 16430602
TI  - How adults' access to outpatient physician services relates to the local supply
      of primary care physicians in the rural southeast.
AB  - OBJECTIVE: To examine how access to outpatient medical care varies with local
      primary care physician densities across primary care service areas (PCSAs) in the
      rural Southeast, for adults as a whole and separately for the elderly and poor.
      DATA SOURCES: Access data from a 2002 to 2003 telephone survey of 4,311 adults
      living in 298 PCSAs within 150 rural counties in eight Southeastern states were
      linked geographically with physician practice location data from the American
      Medical and American Osteopathic Associations and population data from the U.S.
      Census. STUDY DESIGN: In a cross-sectional study design, we used a series of
      logistic regression models to assess how 26 measures of various aspects of access
      to outpatient physician services varied for subjects arranged into five groups
      based on the population-per-physician ratios of the PCSAs where they lived.
      PRINCIPAL FINDINGS: Among adults as a whole, more individuals reported traveling
      over 30 minutes for outpatient care in PCSAs with more than 3,500 people per
      physician than in PCSAs with fewer than 1,500 people per physician (39.1 versus
      18.5 percent, p<.001) and more reported travel difficulties. Otherwise, PCSA
      density of primary care physicians was unrelated to reported barriers to care,
      unrelated to people's satisfaction with care, and unrelated to indicators of
      people's use of services. Use rates of six recommended preventive health services
      varied in no consistent direction with physician densities. Among the elderly,
      only the proportion traveling over 30 minutes for care was greater in areas with
      lowest physician densities. Among subjects covered under Medicaid or uninsured,
      lower local physician densities were associated with longer travel time,
      difficulties with travel and reaching one's physician by phone, and two areas of
      dissatisfaction with care. CONCLUSIONS: For adults as a whole in the rural South
      and for the elderly there, low local primary care physician densities are
      associated with travel inconvenience but not convincingly with other aspects of
      access to outpatient care. Access for those insured under Medicaid and the
      uninsured, however, is in more ways sensitive to local physician densities.

PMID- 16430603
TI  - Disparities in use of and unmet need for therapeutic and supportive services
      among school-age children with functional limitations: a comparison across
      settings.
AB  - OBJECTIVES: To determine whether family resources predict use of therapeutic and
      supportive services and unmet needs in medical versus educational settings. DATA
      SOURCE: Children 5-17 years of age with at least one functional limitation
      (n=3,434) from the 1994 to 1995 Disability Supplement to the U.S. National Health
      Interview Survey. STUDY DESIGN: Family resources included the child's type of
      health insurance, household education level, and poverty status. Therapeutic
      services included audiology; social work; occupational, physical, or speech
      therapy. Supportive services included special equipment, personal care
      assistance, respite care, transportation, or environmental modifications. Need
      was controlled by child health status and the severity and type of functional
      limitation(s). Age, gender, race/ethnicity, family size, and structure were
      covariates. DATA ANALYSIS METHODS: Logistic regression provided estimates of
      associations between-family resources and use of or unmet need for therapeutic
      and supportive services. Multinomial methods were used to determine therapeutic
      service outcomes in medical versus educational settings. PRINCIPAL FINDINGS:
      Children with public insurance were two to three times more likely to use
      services than children with private or no insurance regardless of type of
      service. Household education and public insurance were associated with supportive
      and therapeutic service use, but for therapeutic services only among children
      receiving services beyond the school setting. Household education predicted unmet
      need for both types of services and therapeutic services across settings.
      Findings should be interpreted cautiously, given the survey's dependence on
      respondent report to define the need for services and the potential for
      overrepresentation of children with more severe needs in the public insurance
      category. CONCLUSIONS: Disparities in the use of services by household education
      level and by type of health insurance across service settings suggests
      inequitable access among the U.S. policies and programs serving children with
      functional limitations. Family income and education appear to give families an
      advantage in obtaining services and in identifying a child's unmet need.

PMID- 16430604
TI  - The effects of child-only insurance coverage and family coverage on health care
      access and use: recent findings among low-income children in California.
AB  - OBJECTIVE: To compare the extent with which child-only and family coverage (child
      and parent insured) ensure health care access and use for low income children in
      California and discuss the policy implications of extending the State Children's
      Health Insurance Program (California's Healthy Families) to uninsured parents of
      child enrollees. DATA SOURCES/SETTING: We used secondary data from the 2001
      California Health Interview Survey (CHIS), a representative telephone survey.
      STUDY DESIGN: We conducted a cross-sectional study of 5,521 public health
      insurance-eligible children and adolescents and their parents to examine the
      effects of insurance (family coverage, child-only coverage, and no coverage) on
      measures of health care access and utilization including emergency room visits
      and hospitalizations. DATA COLLECTION: We linked the CHIS adult, child, and
      adolescent datasets, including the adolescent insurance supplement. FINDINGS:
      Among the sampled children, 13 percent were uninsured as were 22 percent of their
      parents. Children without insurance coverage were more likely than children with
      child-only coverage to lack a usual source of care and to have decreased use of
      health care. Children with child-only coverage fared worse than those with family
      coverage on almost every access indicator, but service utilization was
      comparable. CONCLUSIONS: While extending public benefits to parents of children
      eligible for Healthy Families may not improve child health care utilization
      beyond the gains that would be obtained by exclusively insuring the children,
      family coverage would likely improve access to a regular source of care and
      private sector providers, and reduce perceived discrimination and breaks in
      coverage. These advantages should be considered by states that are weighing the
      benefits of expanding health insurance to parents.

PMID- 16430605
TI  - Parent-identified barriers to pediatric health care: a process-oriented model.
AB  - OBJECTIVE: To further understand barriers to care as experienced by health care
      consumers, and to demonstrate the importance of conjoining qualitative and
      quantitative health services research. DATA SOURCES: Transcripts from focus
      groups conducted in San Diego with English- and Spanish-speaking parents of
      children with special health care needs. STUDY DESIGN: Participants were asked
      about the barriers to care they had experienced or perceived, and their
      strategies for overcoming these barriers. Using elementary anthropological
      discourse analysis techniques, a process-based conceptual model of the parent
      experience was devised. PRINCIPAL FINDINGS: The analysis revealed a parent
      motivated model of barriers to care that enriched our understanding of
      quantitative findings regarding the population from which the focus group sample
      was drawn. Parent-identified barriers were grouped into the following six
      temporally and spatially sequenced categories: necessary skills and prerequisites
      for gaining access to the system; realizing access once it is gained; front
      office experiences; interactions with physicians; system arbitrariness and
      fragmentation; outcomes that affect future interaction with the system. Key to
      the successful navigation of the system was parents' functional biomedical
      acculturation; this construct likens the biomedical health services system to a
      cultural system within which all parents/patients must learn to function
      competently. CONCLUSIONS: Qualitative analysis of focus group data enabled a
      deeper understanding of barriers to care--one that went beyond the traditional
      association of marker variables with poor outcomes ("what") to reveal an
      understanding of the processes by which parents experience the health care system
      ("how,""why") and by which disparities may arise. Development of such process
      oriented models furthers the provision of patient-centered care and the creation
      of interventions, programs, and curricula to enhance such care. Qualitative
      discourse analysis, for example using this project's widely applicable protocol
      for generating experientially based models, can enhance our knowledge of the
      parent/patient experience and aid in the development of more powerful
      conceptualizations of key health care constructs.

PMID- 16430606
TI  - Effect of Social Security payments on substance abuse in a homeless mentally ill
      cohort.
AB  - OBJECTIVES: To determine whether receipt of social supplemental security income
      (SSI) or Social Security disability income (SSDI) disability payments is
      associated with increased drug and alcohol use. DATA SOURCES/STUDY SETTING:
      Secondary analysis of data from 6,199 participants in the Access to Community
      Care and Effective Social Supports and Services demonstration for the homeless
      mentally ill. DESIGN: Observational, 12-month, cohort study completed over 4
      years. Substance abuse and other outcomes were compared between the participants
      who did not receive SSI or SSDI during the 12-month study, those newly awarded
      benefits, and those without benefits throughout the 12 months. DATA COLLECTION
      METHODS: Social Security administrative records were used to corroborate Social
      Security benefit status. Drug and alcohol use were measured by self-report and
      clinician ratings. PRINCIPAL FINDINGS: Participants who did not receive benefits
      significantly reduced their substance use over time. In generalized estimating
      equations models that adjusted for potentially confounding covariates,
      participants who newly received Social Security benefits showed no greater drug
      use than those without benefits but had significantly more days housed and fewer
      days employed. Participants whose benefits antedated the demonstration and
      continued during the 12 months had more clinician-rated drug use over time than
      those without benefits. CONCLUSIONS: In this vulnerable population, participants
      with newly awarded benefits did not have any different drug use changes than
      those without benefits, and had relatively more days housed. The hypothesis that
      Social Security benefits facilitate drug use was not supported by longitudinal
      data in this high-risk population.

PMID- 16430607
TI  - Benefit-cost in the California treatment outcome project: does substance abuse
      treatment "pay for itself"?
AB  - OBJECTIVE: To examine costs and monetary benefits associated with substance abuse
      treatment. DATA SOURCES: Primary and administrative data on client outcomes and
      agency costs from 43 substance abuse treatment providers in 13 counties in
      California during 2000-2001. STUDY DESIGN: Using a social planner perspective,
      the estimated direct cost of treatment was compared with the associated monetary
      benefits, including the client's costs of medical care, mental health services,
      criminal activity, earnings, and (from the government's perspective) transfer
      program payments. The cost of the client's substance abuse treatment episode was
      estimated by multiplying the number of days that the client spent in each
      treatment modality by the estimated average per diem cost of that modality.
      Monetary benefits associated with treatment were estimated using a pre
      posttreatment admission study design, i.e., each client served as his or her own
      control. DATA COLLECTION: Treatment cost data were collected from providers using
      the Drug Abuse Treatment Cost Analysis Program instrument. For the main sample of
      2,567 clients, information on medical hospitalizations, emergency room visits,
      earnings, and transfer payments was obtained from baseline and 9-month follow-up
      interviews, and linked to information on inpatient and outpatient mental health
      services use and criminal activity from administrative databases. Sensitivity
      analyses examined administrative data outcomes for a larger cohort (N=6,545) and
      longer time period (1 year). PRINCIPAL FINDINGS: On average, substance abuse
      treatment costs $1,583 and is associated with a monetary benefit to society of
      $11,487, representing a greater than 7:1 ratio of benefits to costs. These
      benefits were primarily because of reduced costs of crime and increased
      employment earnings. CONCLUSIONS: Even without considering the direct value to
      clients of improved health and quality of life, allocating taxpayer dollars to
      substance abuse treatment may be a wise investment.

PMID- 16430608
TI  - Impact of institutional review board practice variation on observational health
      services research.
AB  - OBJECTIVE: To describe, qualitatively and quantitatively, the impact of a review
      by multiple institutional review boards (IRBs) on the conduct of a multisite
      observational health services research study. DATA SOURCE AND SETTING: Primary
      data collection during 2002, 2003, and 2004 at 43 United States Department of
      Veterans Affairs (VA) primary care clinics. DESIGN: Explanatory sequential mixed
      methods design incorporating qualitative and quantitative elements in sequence.
      DATA COLLECTION AND ABSTRACTION METHODS: Field notes and documents collected by
      research staff during a multisite observational health services research study
      were used in thematic analysis. Themes were quantified descriptively and merged
      with timeline data. PRINCIPAL FINDINGS: Approximately 4,680 hours of staff time
      over a 19-month period were devoted solely to the IRB process. Four categories of
      phenomena impacting research were observed: (1) Recruitment, retention, and
      communication issues with local site principal investigators (PIs). Local PIs had
      no real role but were required by IRBs. Twenty-one percent of sites experienced
      turnover in local PIs, and local PI issues added significant delay to most sites.
      (2) Wide variation in standards applied to review and approval of IRB
      applications. The study was designed to be qualified under U.S. government
      regulations for expedited review. One site exempted it from review (although it
      did not qualify for exemption), 10 granted expedited review, 31 required full
      review, and one rejected it as being too risky to be permitted. Twenty-three
      required inapplicable sections in the consent form and five required HIPAA
      (Health Insurance Portability and Accountability Act of 1996) consent from
      physicians although no health information was asked of them. Twelve sites
      requested, and two insisted upon, provisions that directly increased the risk to
      participants. (3) Multiple returns for revision of IRB applications, consent
      documents, and ancillary forms. Seventy-six percent of sites required at least
      one resubmission, and 15 percent of sites required three or more (up to six)
      resubmissions. Only 12 percent of sites required any procedural or substantive
      revision; most resubmissions were editorial changes to the wording of the consent
      document. (4) Process failures (long turnaround times, lost paperwork, difficulty
      in obtaining necessary forms, unavailability of key personnel at IRBs). The
      process required from 52 to 798 (median 286) days to obtain approval at each
      site. CONCLUSIONS: Several features of the IRB system as currently configured
      impose costly burdens of administrative activity and delay on observational
      health services research studies, and paradoxically decrease protection of human
      subjects. Central review with local opt-out, cooperative review, or a system of
      peer review could reduce costs and improve protection of human subjects.

PMID- 16430609
TI  - Does date stamping ICD-9-CM codes increase the value of clinical information in
      administrative data?
AB  - CONTEXT: Comorbidity measures are designed to exclude complications when they map
      International Classification of Diseases (ICD-9-CM) codes to diagnostic
      categories. The use of data fields that indicates whether each secondary
      diagnosis was present at the time of hospital admission may lead to the more
      accurate identification of preexisting conditions. OBJECTIVE: To examine the rate
      of misclassification of ICD-9-CM codes into diagnostic categories by the
      Dartmouth-Manitoba adaptation of the Charlson index and by the Elixhauser
      comorbidity algorithm. DATA SOURCE: Analysis of 178,838 patients in the
      California State Inpatient Database (CA SID) admitted in 2000 for one of seven
      major medical and surgical conditions. The CA SID includes a condition present at
      admission (CPAA) modifier for each ICD-9-CM code. STUDY DESIGN: The
      Dartmouth/Charlson index and the Elixhauser comorbidity measure were used to map
      the ICD-9-CM codes into diagnostic categories for patients in each study
      population. We calculated the misclassification rate for each mapping algorithm,
      using information from the CPAA as the "gold standard." PRINCIPAL FINDINGS: The
      Dartmouth/Charlson index underestimated the prevalence of hemiplegia/paraplegia
      by 70 percent, cerebrovascular disease by 70 percent, myocardial infarction by 65
      percent, congestive heart failure (CHF) by 45 percent, and peptic ulcer disease
      by 34 percent. The Elixhauser algorithm misclassified complications as
      preexisting conditions for 43 percent of the coagulopathies, 25 percent of the
      fluid and electrolyte disorders, 18 percent of the cardiac arrhythmias, 18
      percent of the cardiac arrhythmias, and 9 percent of the cases of CHF.
      CONCLUSION: Adding the CPAA modifier to administrative data would significantly
      enhance the ability of the Dartmouth/Charlson index and of the Elixhauser
      algorithm to map ICD-9-CM codes to diagnostic categories accurately.

PMID- 16430610
TI  - Overcoming bias in estimating the volume-outcome relationship.
AB  - OBJECTIVE: To examine the effect of hospital volume on 30-day mortality for
      patients with congestive heart failure (CHF) using administrative and clinical
      data in conventional regression and instrumental variables (IV) estimation
      models. DATA SOURCES: The primary data consisted of longitudinal information on
      comorbid conditions, vital signs, clinical status, and laboratory test results
      for 21,555 Medicare-insured patients aged 65 years and older hospitalized for CHF
      in northeast Ohio in 1991-1997. STUDY DESIGN: The patient was the primary unit of
      analysis. We fit a linear probability model to the data to assess the effects of
      hospital volume on patient mortality within 30 days of admission. Both
      administrative and clinical data elements were included for risk adjustment.
      Linear distances between patients and hospitals were used to construct the
      instrument, which was then used to assess the endogeneity of hospital volume.
      PRINCIPAL FINDINGS: When only administrative data elements were included in the
      risk adjustment model, the estimated volume-outcome effect was statistically
      significant (p=.029) but small in magnitude. The estimate was markedly attenuated
      in magnitude and statistical significance when clinical data were added to the
      model as risk adjusters (p=.39). IV estimation shifted the estimate in a
      direction consistent with selective referral, but we were unable to reject the
      consistency of the linear probability estimates. CONCLUSIONS: Use of only
      administrative data for volume-outcomes research may generate spurious findings.
      The IV analysis further suggests that conventional estimates of the volume
      outcome relationship may be contaminated by selective referral effects. Taken
      together, our results suggest that efforts to concentrate hospital-based CHF care
      in high-volume hospitals may not reduce mortality among elderly patients.

PMID- 16430611
TI  - The reliability of survey assessments of characteristics of medical clinics.
AB  - OBJECTIVE: To assess the reliability of survey measures of organizational
      characteristics based on reports of single and multiple informants. DATA SOURCE:
      Survey of 330 informants in 91 medical clinics providing care to HIV-infected
      persons under Title III of the Ryan White CARE Act. STUDY DESIGN: Cross-sectional
      survey. DATA COLLECTION METHODS: Surveys of clinicians and medical directors
      measured the implementation of quality improvement initiatives, priorities
      assigned to aspects of HIV care, barriers to providing high-quality HIV care, and
      quality improvement activities. Reliability of measures was assessed using
      generalizability coefficients. Components of variance and clinician-director
      differences were estimated using hierarchical regression models with survey items
      and informants nested within organizations. PRINCIPAL FINDINGS: There is
      substantial item- and informant-related variability in clinic assessments that
      results in modest or low clinic-level reliability for many measures. Directors
      occasionally gave more optimistic assessments of clinics than did clinicians.
      CONCLUSIONS: For most measures studied, obtaining adequate reliability requires
      multiple informants. Using multiple-item scales or multiple informants can
      improve the psychometric performance of measures of organizational
      characteristics. Studies of such characteristics should report the organizational
      level reliability of the measures used.

PMID- 16430612
TI  - Psychometric properties of the Dutch version of the Hospital-level Consumer
      Assessment of Health Plans Survey instrument.
AB  - OBJECTIVES: To assess the reliability and validity of a translated version of the
      American Hospital-level Consumer Assessment of Health Plans Survey (H-CAHPS)
      instrument for use in Dutch health care. DATA SOURCES/STUDY SETTING: Primary
      survey data from adults aged 18 years or more who were recently discharged from
      two multispecialty city hospitals in the Netherlands. STUDY DESIGN: We used
      forward and backward translation procedures and a panel of experts to adapt the
      66-item pilot H-CAHPS into a 70-item Dutch instrument. Descriptive statistics and
      standard psychometric methods were then used to test the reliability and validity
      of the new instrument. DATA COLLECTION: From late November 2003 to early January
      2004, the survey was administered by mail to 1,996 patients discharged within the
      previous 2 months. PRINCIPAL FINDINGS: Analyses supported the reliability and
      validity of the following 7-factor H-CAHPS structure for use in Dutch hospitals:
      on doctor's communication, nurses' communication, discharge information,
      communication about medication, pain control, physical environment of hospital,
      and nursing services. The internal consistency reliability of the scales ranged
      from 0.60 to 0.88. Items related to "family receiving help when on
      visit,""hospital staff introducing self," and "admission delays" did not improve
      the psychometric properties of the new instrument. CONCLUSIONS: These findings
      suggest that the H-CAHPS instrument is reliable and valid for use in the Dutch
      context. However, more research will be needed to support its equivalence to the
      United States version, and its use for between-hospital comparisons.

PMID- 16430614
TI  - Nanotechnology: potential applications in urology.

PMID- 16430615
TI  - A case for screening for renal cancer.

PMID- 16430616
TI  - Real-time multiple microsensor tissue recognition and its potential application
      in the management of prostate cancer.

PMID- 16430617
TI  - Prostate biopsy: to stop anticoagulation or not?

PMID- 16430618
TI  - Lymphadenectomy for invasive bladder cancer: I. historical perspective and
      contemporary rationale.

PMID- 16430619
TI  - Lymphadenectomy for invasive bladder cancer. II. technical aspects and prognostic
      factors.

PMID- 16430620
TI  - A simple method for teaching about voiding disorders.

PMID- 16430621
TI  - Recent improvements in transurethral high-frequency electrosurgery of the
      prostate.

PMID- 16430622
TI  - Bicalutamide 150 mg plus standard care vs standard care alone for early prostate
      cancer.
AB  - OBJECTIVE: To evaluate, in the ongoing Early Prostate Cancer (EPC) trial
      programme, the efficacy and tolerability of bicalutamide 150 mg once daily in
      addition to standard care for localized or locally advanced, nonmetastatic
      prostate cancer. PATIENTS AND METHODS: The EPC programme comprises three
      randomized, double-blind, placebo-controlled trials designed for combined
      analysis. Following standard care, 8113 men with localized (T1-2, N0/Nx) or
      locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) received
      oral bicalutamide 150 mg once daily or oral placebo. The primary endpoints were
      progression-free survival (PFS) and overall survival. RESULTS: The large EPC
      trial programme is defining men who benefit or do not from early or adjuvant
      antiandrogen therapy. At a median follow-up of 7.4 years, in localized disease
      there is no benefit to PFS by adding bicalutamide to standard care, and there is
      a trend (hazard ratio, HR, 1.16; 95% confidence intervals, CI, 0.99-1.37; P =
      0.07) towards decreased survival in patients otherwise undergoing watchful
      waiting. However, in locally advanced disease, bicalutamide significantly
      improved PFS irrespective of standard care. Bicalutamide significantly improved
      overall survival in patients receiving radiotherapy (HR 0.65; 95% CI 0.44-0.95; P
      = 0.03); this was driven by a lower risk of prostate cancer-related deaths.
      Bicalutamide produced a trend towards improved overall survival in patients with
      locally advanced disease otherwise undergoing watchful waiting (HR 0.81; 95% CI
      0.66-1.01; P = 0.06). No survival difference was evident in the prostatectomy
      subgroup. CONCLUSIONS: This ongoing programme is clarifying the role of early or
      adjuvant antiandrogen therapy in prostate cancer. Patients with localized disease
      do not appear to derive clinical benefit from added bicalutamide. However, adding
      bicalutamide 150 mg to standard care provides significant clinical benefits in
      patients with locally advanced prostate cancer, irrespective of primary therapy.

PMID- 16430623
TI  - Factors predisposing to the development of anastomotic strictures in a single
      surgeon series of radical retropubic prostatectomies.
AB  - OBJECTIVE: To determine the rate of anastomotic stricture (AS) after radical
      retropubic prostatectomy (RRP) performed by one experienced surgeon, and to
      identify factors predisposing to its formation. PATIENTS AND METHODS: In all, 708
      men were prospectively monitored for the development of AS after RRP. Potential
      risk factors for AS were analysed. RESULTS: There were no significant differences
      in age, Gleason score, nerve-sparing status, intraoperative blood loss, degree of
      extravasation on initial cystography, or duration of the indwelling urinary
      catheter between men who developed AS and men who did not. The mean postoperative
      blood loss was significantly higher in men who developed AS. The incidence of AS
      was also significantly higher in men whose bladder necks were reconstructed more
      narrowly. CONCLUSION: The amount of bleeding and the calibre of the reconstructed
      bladder neck were significantly associated with AS formation after RRP. The
      development of a haematoma from bleeding might explain the increased likelihood
      of AS. The mechanism of AS formation is unrelated to the degree of urinary
      extravasation on cystography, providing that a urinary catheter is left
      indwelling until extravasation resolves.

PMID- 16430624
TI  - Location of a positive biopsy as a predictor of surgical margin status and
      extraprostatic disease in radical prostatectomy.
AB  - OBJECTIVE: To investigate whether the location of preoperative biopsy positive
      cores can identify patients at higher risk of a positive surgical margin (SM) and
      extraprostatic extension (EPE) at radical retropubic prostatectomy (RRP).
      PATIENTS AND METHODS: We retrospectively reviewed the clinical and pathological
      data of 371 patients who had a RRP for biopsy confirmed prostate cancer between
      January 2000 and October 2003. RESULTS: A positive biopsy at the apex was not
      predictive of a positive apical SM or EPE. However, a positive biopsy at the base
      was predictive of a positive basal SM and EPE. A positive SM, in turn, correlated
      with EPE on final pathology. Positive basal SM correlated with EPE in 75% of
      cases whereas positive apical SM showed EPE in only 33% (P < 0.02). CONCLUSION: A
      positive biopsy core at the base appears to correlate with a positive basal SM
      and EPE. A positive basal SM correlates with EPE at a higher rate than apical
      SMs.

PMID- 16430625
TI  - Site of local anaesthesia in transrectal ultrasonography-guided 12-core prostate
      biopsy: does it make a difference?
AB  - OBJECTIVE: To prospectively compare the efficacy of bi-basal vs bi-apical
      periprostatic nerve block (PPNB) during 12-core prostate biopsy guided by
      transrectal ultrasonography (TRUS), and to evaluate the pain experienced on
      inserting the probe compared to the biopsy procedure, as PPNB with lignocaine
      local anaesthesia has been used for over a decade for minimizing pain during
      prostatic biopsy. PATIENTS AND METHODS: In all, 143 men who were to have a TRUS
      guided prostate biopsy were systematically randomized to two groups, to receive
      PPNB at the apex or base. A 10-cm visual analogue score was used to record the
      pain experienced during probe insertion, the biopsy and just before to leaving
      the department . RESULTS: The mean pain score on biopsy in the apical group was
      similar to that of the basal group (apex 1.9, base 1.6, P = 0.36). Probe
      introduction produced a significantly higher pain score (probe 2.2, biopsy 1.7, P
      < 0.001) than at the biopsy. CONCLUSIONS: Patients who experienced greater pain
      with the introduction of the probe also reported more pain with the biopsy
      procedure. The site of local anaesthetic before prostatic biopsy showed no
      significant difference in pain scores. Older men tolerated the procedure better.
      Analgesia after PPNB at near either the apex or base appears equal, regardless of
      the site of injection. We suggest that topical perianal anaesthetic agents could
      significantly reduce not only pain perception, but also improve tolerance.

PMID- 16430626
TI  - The increased rate of prostate specific antigen testing has not affected prostate
      cancer presentation in an inner city population in the UK.
AB  - OBJECTIVE: To assess whether the increased use of prostate-specific antigen (PSA)
      testing over the last 15 years has changed the way prostate cancer presents in an
      inner city UK population, where PSA screening rates might be expected to be lower
      than in epidemiological studies based in North America, where there is a
      significant tendency to a localized stage and earlier age at diagnosis. PATIENTS
      AND METHODS: The study comprised a 5-year retrospective and 5-year prospective
      analysis of data on 704 men diagnosed with prostate cancer over the 10-year
      period since the introduction of PSA testing (1994-2003). RESULTS: The median
      (range) age at presentation remained unchanged, at 72 (45-94) years; the PSA
      level at diagnosis was 20-46 microg/L, with a steady decline after 1997. There
      was no significant change in stage at diagnosis; overall, 38 (20-44)% presented
      with clinically localized disease, 37 (31-48)% with locally advanced and 25 (18
      29)% with metastatic disease. The Gleason grade changed significantly, with more
      moderately differentiated tumours and a decline in well-differentiated cancers.
      Closer examination showed this to have been due to a change in diagnostic
      practice rather than a true population trend. PSA testing increased over the 10
      years of the study (2.35 times), with requests from general practitioners rising
      seven times, compared with urologists or other hospital doctors (1.25 and 2.3
      times, respectively). Community PSA testing remained lower than in other reported
      UK series, which may be explained in part by the lower socio-economic status of
      the population assessed. CONCLUSION: There was no apparent change in patient age
      or tumour stage in men presenting with prostate cancer over a 10-year period
      after the introduction of PSA testing. While there was an increase in PSA testing
      during the study period, the testing rate remains much lower than in other
      reported series from the UK.

PMID- 16430627
TI  - Prostate tissue and leukocyte levels of n-3 polyunsaturated fatty acids in men
      with benign prostate hyperplasia or prostate cancer.
AB  - OBJECTIVE: To compare the levels of n-3 polyunsaturated fatty acids (PUFAs) in
      leukocytes and prostate tissue in men with prostate cancer or benign prostatic
      hyperplasia (BPH), as dietary intake of n-3 PUFAs has been linked to the risk of
      prostate cancer; the prostate-specific antigen (PSA) level was also compared to
      prostate tissue levels of n-3 PUFAs. PATIENTS AND METHODS: Prostate tissue was
      obtained and leukocytes isolated from 20 men with prostate cancer and 35 with
      BPH. The n-3 PUFAs alpha-linolenic acid (ALA), eicosapentanoic acid (EPA) and
      docosahexaenoic acid (DHA) were measured in prostate tissue and in peripheral
      blood leukocytes using gas chromatography. PSA levels were measured in all of the
      men. RESULTS: There was a strong positive correlation between EPA and DHA in
      leukocytes and in prostate tissue (EPA: r = 0.80, DHA: r = 0.53, both P < 0.001)
      in all the men, whereas there was no association between the content of ALA in
      leukocytes and in prostate tissue (r = -0.15). Men with BPH had similar levels of
      ALA in leukocytes and in prostate tissue, but men with prostate cancer had more
      ALA in prostate tissue than in leukocytes. The PSA level was significantly
      positively correlated with ALA level in prostate tissue (r = 0.42, P < 0.01) but
      there was no significant correlation between PSA level and EPA and DHA levels.
      There were no significant correlations between PSA level and n-3 PUFA levels in
      leukocytes. CONCLUSION: Dietary intake of the marine n-3 PUFAs reflected in EPA
      and DHA levels in leukocytes are also reflected in EPA and DHA levels in prostate
      tissue in men with and without prostate cancer. However, there is a discrepancy
      between the levels of ALA in leukocytes and in prostate tissue, with higher
      levels in men with prostate cancer. This is in accordance with the strong
      positive association between PSA and ALA levels in prostate tissue. This study
      therefore does not support the hypothesis that intake of marine n-3 PUFAs might
      protect against prostate cancer, but lends support to the deleterious role of ALA
      in the development of prostate cancer.

PMID- 16430628
TI  - Twelve-month self-reported quality of life after retropubic radical
      prostatectomy: a prospective study with Rand 36-Item Health Survey (Short Form
      36).
AB  - OBJECTIVES: To evaluate the health-related quality of life (HRQoL) in patients
      undergoing retropubic radical prostatectomy (RRP) for clinically localized
      prostate cancer. PATIENTS AND METHODS: From February 2002 to September 2003 all
      patients undergoing RRP in our department were invited to participate in the
      study; the data from 75 of them comprised the present analysis. For evaluating
      HRQoL the RAND 36-Item Health Survey (SF-36) was used. RESULTS: Comparing the
      baseline scores of the SF-36 domains to those at 3, 6 and 12 months, there was a
      statistically significant difference in 'physical function', 'role limitations
      due to physical health problems', 'role limitations due to emotional problems',
      and 'energy/fatigue'. There were no statistically significant changes in the
      follow-up values for the other scales of the questionnaire. However, the baseline
      scores overlapped the 12-month follow-up values for all the SF-36 scales. The
      mean SF-36 scores reported by incontinent patients were lower than those of the
      continent patients, although this trend was not statistically significant. At the
      12-month follow-up some variables were independent predictors of lower mean
      scores of some SF-36 scales, i.e. age >65 years, education level less than
      secondary school, pathological extracapsular extension of cancer and erectile
      dysfunction. CONCLUSION: At 1 year after RRP, HRQoL levels in each of the SF-36
      domains overlapped those of the baseline in >80% of patients. The age,
      educational level of patients, local extension of the tumour, and erectile
      dysfunction could significantly affect the HRQoL scores.

PMID- 16430629
TI  - High-dose interleukin-2 immunotherapy is safe for patients with metastatic renal
      cell carcinoma on dialysis.
AB  - OBJECTIVE: To report our experience of high-dose interleukin-2 immunotherapy for
      patients with metastatic renal cell carcinoma (RCC) on haemodialysis. PATIENTS
      AND METHODS: Two anephric patients with metastatic RCC on haemodialysis received
      interleukin-2 (600,000 IU/kg) every 8 h for a maximum of 14 doses. The patients
      rested for 9 days and cycles were repeated as tolerated. A nephrologist followed
      the patients during treatment and they received nearly daily haemodialysis.
      RESULTS: These two cases were treated with high-dose interleukin-2 and had no
      unusual toxicity or adverse events. The first patient tolerated five, five, four,
      four and one dose of interleukin-2 over five cycles. He had a partial response to
      treatment with a decrease in size of a mediastinal mass, but ultimately developed
      progressive disease and died 32 months later. The second patient had four cycles
      of interleukin-2 (13, 13, 14 and nine doses). He initially maintained stable
      disease throughout treatment, but the disease ultimately progressed and he died
      19 months later. CONCLUSIONS: We recommend considering high-dose interleukin-2
      immunotherapy in highly selected dialysis patients with metastatic RCC. Further
      study is required to determine the safety, efficacy and optimum dosing in this
      group.

PMID- 16430630
TI  - Urinary retention in women: its causes and management.
AB  - OBJECTIVE: To report the experience of the last 4 years from a centre to which
      women with voiding difficulties and urinary retention were referred nationally,
      describing what investigations were helpful in making a diagnosis and the
      management strategies used. PATIENTS AND METHODS: Women with voiding difficulties
      and urinary retention remain a diagnostic and management challenge, and those
      with no anatomical or neurological basis for their symptoms may be dismissed,
      assuming that their retention has a psychogenic basis. The finding of an
      electromyographic (EMG) abnormality of the striated urethral sphincter explaining
      their disorder (Fowler's syndrome) has led to the referral of women for
      consideration of that diagnosis. Thus we audited the referrals to the centre over
      a 4-year period of such women. RESULTS: In all, 247 women (mean age 35 years)
      with complete (42%) or partial retention (58%) were referred; 175 (71%) had
      urethral pressure profilometry, 141 (57%) had a transvaginal ultrasonographic
      measurement of the sphincter volume, and 95 (39%) had sphincter EMG. The mean
      maximum urethral closure pressure difference between patients with an EMG
      abnormality (101.5 cmH(2)O) and the patients with known other causes of voiding
      dysfunction (66.2 cmH(2)O) was 35.3 cmH(2)O (P < 0.05). In patients with complete
      retention there was a significant difference in sphincter volume between those
      who were EMG-positive (2.14 mL) or EMG-negative (1.64 mL) (P < 0.05). CONCLUSION:
      These investigations helped to classify the cause of retention in two-thirds of
      cases. The commonest diagnosis was Fowler's syndrome, in which sacral nerve
      stimulation is the only intervention that restores voiding.

PMID- 16430631
TI  - Evidence of occult dysautonomia in Fowler's syndrome: alteration of
      cardiovascular autonomic function tests in female patients presenting with
      urinary retention.
AB  - OBJECTIVE: To assess the hypothesis that an occult impairment of the autonomic
      system might represent one of the mechanisms of urinary disturbance in Fowler's
      syndrome (FS), in which the pathophysiology of urinary retention is the
      predominant feature. PATIENTS AND METHODS: We prospectively investigated 10 women
      (mean age 43.7 years) with FS, diagnosed by assessing both voiding-phase
      dysfunction (complete or incomplete retention with a residual urine volume of
      >150 mL, and a maximum flow rate of <15 mL/s), abnormalities of striated urethral
      sphincter electromyography (decelerating bursts and complex repetitive
      discharges), the presence of polycystic ovaries and absence of any apparent usual
      causes (obstructive, neurological diseases). The women had a urodynamic
      investigation, electromyographic examination, cystoscopy, brain and spinal cord
      magnetic resonance imaging (MRI) and cardiovascular autonomic function tests
      (CAFTs, i.e. heart rate variability to deep breathing, cold-pressor test,
      Valsalva ratio, blood pressure response to standing, and sympathetic skin
      responses), for parasympathetic and sympathetic functions. Evidence of
      dysautonomia, as classically described, was defined by two or more positive
      CAFTs. RESULTS: The mean duration of symptoms was 7.9 years; there was urinary
      retention in six patients (one complete and five incomplete) and the other four
      complained of straining to void, diminished stream and hesitancy. Five patients
      were using intermittent self-catheterization. Six patients had two or more
      positive CAFTs and were considered to have dysautonomia. In all 10 women the
      clinical neurological and urological examinations were normal with no apparent
      clinical symptoms of dysautonomia (blurred vision, pupil abnormalities, clinical
      manifestations of postural hypotension, gastrointestinal symptoms). Brain and
      spinal cord MRI, cystoscopy, bladder and kidney ultrasonography, sacral-evoked
      latencies and cortical-evoked responses after pudendal nerve stimulation were
      normal. CONCLUSION: There was an occult impairment of the autonomic system in
      women with FS; this condition might be a pure bladder expression of a generalized
      but occult dysautonomia, which in some cases might be diagnosed using CAFTs.

PMID- 16430632
TI  - Reduction of moderate-to-large cystocele during urodynamic evaluation using a
      vaginal gauze pack: 8-year experience.
AB  - OBJECTIVE: To determine the effect of cystocele reduction by a vaginal gauze pack
      on urodynamic studies (UDS). PATIENTS AND METHODS: UDS from consecutive women
      with symptomatic pelvic organ prolapse were reviewed. The protocol included a
      'fill-void' study with a vaginal gauze pack, and then repeated without the pack.
      Tracings were categorized based on filling cystometrograms (CMGs) and pressure
      flow studies (PFS). RESULTS: Of 202 women, 121 with a mean (sd) age of 67 (9.4)
      years contributed 221 interpretable 'pack, then no-pack' UDS (111 CMGs and 110
      PFS); 77 of the women had a moderate cystocele and 44 had a large cystocele.
      Eighty-five women had urethral hypermobility (UH), and 36 had a well-supported
      urethra (WSU). The pack unmasked stress urinary incontinence (SUI) in 6% of
      women, with a mean (sd, range) Valsalva leak-point pressure of 54 (22, 23-90)
      cmH(2)O. SUI occurred more often in women with UH than WSU. Detrusor overactivity
      occurred similarly in pack (15%) and no-pack (14%) tracings. Bladder outlet
      obstruction (BOO) was relieved by the pack in 25 studies and caused by the pack
      in four. Women with WSU had BOO more often than those with UH (43% vs 22%, P <
      0.05), regardless of the presence or absence of the pack. CONCLUSION: Unmasked
      SUI by pack reduction was uncommon, presumably due to anterior vaginal wall
      stabilization, as the pack rarely caused BOO. Those with SUI had Valsalva leak
      point pressures suggestive of intrinsic sphincter deficiency. The pack did not
      significantly influence the presence of detrusor overactivity.

PMID- 16430633
TI  - What is the effect of overactive bladder symptoms on woman's quality of life
      during and after first pregnancy?
AB  - OBJECTIVE: To evaluate the effect of overactive bladder symptoms (OAB) on women's
      quality of life (QoL) during and after the first pregnancy, using self-reported
      symptom-based QoL questionnaires. PATIENTS AND METHODS: In a prospective cohort
      study, 474 women were asked to complete four self-reported questionnaires.
      Urogenital symptoms were assessed with the Urogenital Distress Inventory (UDI)
      and the Incontinence Impact Questionnaire (IIQ). A women was considered to
      experience 'dry' OAB if she replied positively to the following two questions:
      'do you experience a strong feeling of urgency to empty your bladder?'; and 'do
      you experience frequent urination?'. A women was considered to experience 'wet'
      OAB if she replied positively to all of the following questions: 'do you
      experience a strong feeling of urgency to empty your bladder?'; 'do you
      experience frequent urination?'; and 'do you experience urine leakage related to
      the feeling of urgency?'. RESULTS: In all, 344 (72.6%) women who returned all
      four questionnaires were included in the analysis. After first childbirth there
      was a rapid decline in the prevalence of dry OAB (45.2% to 7.9%, P < 0.001). In
      pregnancy the prevalence of wet OAB increased significantly, but a year after
      childbirth the prevalence of wet OAB decreased and was similar to that at 12
      weeks of gestation (P = 0.289). Women with wet OAB had higher scores on all IIQ
      domains than those with no OAB symptoms at 36 weeks of gestation. Women with dry
      or wet OAB all had higher scores on the mobility domain than those with no OAB.
      The scores on the physical, social and emotional functioning domains were low,
      suggesting a minimal restriction of lifestyle. CONCLUSION: OAB symptoms are
      common during pregnancy; dry OAB had no negative effect on QoL, whereas wet OAB
      compromised QoL both during and after pregnancy, mainly in the 'mobility' and
      'embarrassment' domains. The urge urinary incontinence symptom in wet OAB seems
      to profoundly compromise QoL. Apparently, in young mothers with wet OAB,
      limitations in mobility are especially stressful and these symptoms can be
      embarrassing.

PMID- 16430634
TI  - A prospective analysis of the diagnostic yield resulting from the attendance of
      4020 patients at a protocol-driven haematuria clinic.
AB  - OBJECTIVE: To clarify the prevalence of disease as determined by age, sex and the
      degree of haematuria at presentation, and to ascertain the merits of using
      ultrasonography (US), i.v. urography (IVU) or both when imaging the upper urinary
      tract, in a prospective cohort of patients attending a protocol-based haematuria
      clinic. PATIENTS AND METHODS: In a two-tier protocol, as a part of first-line
      investigation, all 4020 patients attending the clinic between October 1998 and
      August 2003 had US and flexible cystoscopy. Subsequently, IVU was used where
      indicated following abnormal first-line tests and in patients with persistent
      haematuria where no abnormality had been detected. RESULTS: In all, 2627 men and
      1393 women presented with microscopic (53.2%) or macroscopic haematuria (46.8%).
      The overall prevalence of malignant disease was 12.1%, but for macroscopic
      haematuria it was 18.9% and for microscopic haematuria 4.8%. Age and sex also
      influenced the observed rates of disease. Of the upper tract tumours, 70 were
      identified after abnormal US, with three cases of transitional cell carcinoma
      identified on IVU after a normal US. CONCLUSIONS: The study provides a rationale
      for the appropriate investigation of all patients, moderated by the age, sex and
      degree of haematuria, and the ubiquitous use of US with selective IVU based on
      age, sex and degree of (and persistence of) haematuria.

PMID- 16430635
TI  - Publication rate of abstracts presented at the British Association of Urological
      Surgeons Annual Meeting.
AB  - OBJECTIVE: To determine the number of peer-reviewed publications arising from the
      abstracts presented at the annual meetings of the British Association of
      Urological Surgeons (BAUS), and to assess urological trainees' attitudes to
      research in relationship to the pursuit of Specialist Registrar (SpR) training
      numbers and their perception of academic urology in the UK. METHODS: Publications
      resulting from presentations at the annual meetings of the BAUS 2001 and 2002
      were searched for using the PubMed database. Variables that might influence the
      subsequent publication of abstracts in peer-reviewed journals were analysed.
      Whether institutions from other countries had similar publication rates to those
      in the UK was also assessed. SpRs were interviewed about their motivation to
      convert presentations to publications before and after their appointment to SpR
      training. RESULTS: In July 2004, 142 of 449 abstracts presented at BAUS 2001 and
      2002 were published, giving a publication rate of approximately 42% on Kaplan
      Meier analysis. The rate of publication appeared to continue to the end of the
      period of searching for publications. The publication rate arising from UK
      presentations was lower than that from the non-UK presentations (hazard ratio
      0.75, 95% confidence interval 0.49-1.15, P = 0.14). Publication rates from podium
      and poster presentations were similar. Urology journals accounted for 75% of the
      publications. Of the SpRs evaluated, 83% did research and presented papers to
      obtain a training number rather than because of an inherent interest to pursue an
      academic career. CONCLUSIONS: The conversion rate from BAUS presentation to peer
      reviewed publication at 36 months was similar on Kaplan-Meier analysis to that of
      the American Urological Association (AUA, 38%). Interestingly, the rate of
      publication from the AUA seems to be faster than from BAUS. In addition,
      presentations from outside the UK appeared to be published faster than those from
      the UK. Delegates attending these conferences need to consider this when deciding
      whether a particular presentation will influence their practice. British urology
      requires academics who are interested in pursuing high-quality research, and
      which is presented at major conferences with an intention to publish it in peer
      reviewed journals.

PMID- 16430636
TI  - Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for 'on
      demand' treatment of premature ejaculation.
AB  - OBJECTIVE: To describe the relationship between the pharmacokinetic and
      pharmacodynamic properties of dapoxetine, a drug specifically developed for
      treating premature ejaculation (PE). METHODS: Data from various stages of the
      clinical development programme were analysed using validated methods for
      assessing ejaculatory latency. The clinical characteristics were then compared
      with the pharmacokinetic profile, determined from measured plasma drug
      concentrations. RESULTS: Pharmacodynamic and pharmacokinetic measurements confirm
      that 'on demand' dapoxetine has a rapid onset of action and is rapidly cleared
      after sexual intercourse. CONCLUSION: Dapoxetine may represent the first of a new
      category of selective serotonin transport inhibitors. Although dapoxetine has
      pharmacological similarities to other selective serotonin transport inhibitors,
      its efficacy after acute administration sets it apart and suggests a different
      mode of action. Its physicochemical and pharmacokinetic properties and its
      clinical efficacy make dapoxetine suitable for on-demand treatment of PE.

PMID- 16430637
TI  - Assessment of male sexual function by the Brief Sexual Function Inventory.
AB  - OBJECTIVE: To present normative data from Norway using the Brief Male Sexual
      Function Inventory (BSFI, the first patient self-administered questionnaire to
      assess male sexuality, and used in the USA) in men aged 20-79 years, examine the
      psychometric properties of the BSFI, explore the impact of sexual function and
      other variables on overall sexual satisfaction, and compare American and
      Norwegian normative data. SUBJECTS AND METHODS: From public official address
      lists 3500 men aged 20-79 years were invited to take part in an anonymous
      questionnaire study, including the BSFI. Altogether 1185 (34%) responded, and the
      response rates varied with age. RESULTS: There was increasingly reduced sexual
      function concerning drive, erection, ejaculation, and problem assessment with
      age, and most of the age-effect started at >50 years old. Overall sexual
      satisfaction followed the same trend, but with a weaker association with age.
      Analyses of factor structure and internal consistency of the BSFI supported a one
      factor solution with good internal consistency. Drive, erection, ejaculation, and
      problem assessment explained 28% of the variance in overall sexual satisfaction.
      Being younger and having a sexual partner were also associated with high scores
      of overall sexual satisfaction. American and Norwegian normative data in the BSFI
      dimensions were markedly similar. CONCLUSION: The BSFI is a short and discrete
      screening tool for sexual function, and for most clinical and research purposes
      we recommend using the BSFI as a one-dimensional scale.

PMID- 16430638
TI  - Cigarette smoking is related to a decrease in semen volume in a population of
      fertile men.
AB  - OBJECTIVE: To evaluate the semen quality and hormonal levels in fertile men
      according to their level of cigarette smoking. SUBJECTS AND METHODS: We evaluated
      889 fertile men who came for a vasectomy for sterilization purposes. The men
      included 522 non-smokers, 143 mild smokers (<10 cigarettes/day), 154 moderate
      smokers (11-20/day), and 70 heavy smokers (>20/day). We evaluated sperm
      concentration, motility, motion variables and hormonal levels in these men.
      RESULTS: There were no significant differences among the groups in sperm
      concentration or motility, or in levels of follicle-stimulating hormone,
      luteinizing hormone, or serum total testosterone. Also, sperm motion
      characteristics did not differ across the groups. Semen volume was the only semen
      variable which tended to decrease according to the number of cigarettes smoked.
      CONCLUSIONS: Cigarette smoking had no apparent effect on sperm concentration,
      motility or reproductive hormonal levels, but tended to reduce semen volume.

PMID- 16430639
TI  - Venogenic erectile dysfunction in Klippel-Trenaunay syndrome.
AB  - OBJECTIVE: To report the management of erectile dysfunction (ED) secondary to
      Klippel-Trenaunay syndrome (KTS), a rare congenital vascular disease. PATIENTS
      AND METHODS: Three men (mean age 33 years) with vasogenic ED secondary to KTS
      underwent venous ligation surgery of the affected veins. These men had tried
      various treatments for their ED, including phosphodiesterase type 5 inhibitors
      and intracavernosal injection therapy, with little success. RESULTS: There was
      abnormal penile venous drainage in all three men, probably associated with
      congenital vascular malformation from KTS. After venous ligation the men were
      followed for 5 years and all reported good quality erections satisfactory for
      sexual intercourse. CONCLUSION: ED in men with KTS may be due to venous drainage
      anomalies and if confirmed, venous ligation surgery should be performed as this
      gives the best chance of a complete resolution.

PMID- 16430640
TI  - alpha-Adrenoceptor subtypes in isolated corporal tissue from patients undergoing
      gender re-assignment.
AB  - OBJECTIVE: To investigate the pharmacology and functionality of alpha(1)
      adrenoceptors in human corpus cavernosum, and to determine the predominant
      subtype. MATERIALS AND METHODS: Cavernosal tissue specimens were obtained from
      the penises of 22 men (mean age 37.4 years) removed during gender re-assignment
      surgery. The men had been maintained on long-term oestrogen therapy before
      surgery, to aid the development of secondary feminine characteristics (oestrogen
      treatments were stopped 6 weeks before surgery). Corpus cavernosum strips were
      mounted in organ baths perfused with Krebs' solution. A control concentration
      response curve (CRC) to phenylephrine (a nonselective alpha(1)-agonist) was
      obtained. Then the tissues were incubated with the alpha(1A) antagonist, WB4101;
      the alpha(1B) antagonist, chloroethylclonidine; or the alpha(1D) antagonist BMY
      7378 (all at 1 microm) and the CRC to phenylephrine was repeated. The
      concentration producing a half-maximal response (EC(50)) and pK(B) values
      (logarithm of the dissociation constant, a measure of affinity) were determined.
      RESULTS: WB4101 produced a parallel rightward shift of the CRC to phenylephrine,
      with a pK(B) of 7.49. BMY 7378 also produced a parallel rightward shift of the
      CRC to phenylephrine with a pK(B) of 6.45. Chloroethylclonidine had a similar
      effect on the phenylephrine CRC, with a pK(B) of 5.90. CONCLUSION: Alpha(1)
      adrenoceptors in human cavernosal tissue have a relatively low affinity for BMY
      7378 and chloroethylclonidine, but are more sensitive to WB4101. This confirms
      that the predominant alpha(1)-adrenoceptor subtype in human corpus cavernosum is
      the alpha(1A) subtype and this might help in developing more selective
      antagonists and agonists for managing erectile dysfunction and priapism.

PMID- 16430641
TI  - A 3-year review of The British Association of Urological Surgeons Section of
      Endourology Laparoscopic Nephrectomy Audit.
AB  - OBJECTIVE: To report and compare the data obtained from the BAUS UK national
      laparoscopic nephrectomy audit over the past 3 years. METHODS: Each year,
      consultants performing laparoscopic nephrectomy are invited to submit
      prospectively collected data on all patients so treated at their centres. The
      data from each centre is entered into a nationally established database using a
      standard data-collection sheet. The indications for surgery, and data during and
      after surgery are collected. Since 2001, data were reported on 1294 laparoscopic
      nephrectomies. RESULTS: Over the 3 years, the number of centres returning data
      has increased from 25 to 48. In 2002, data on 263 nephrectomies were returned; by
      2004, this had increased to 598. In all three audits, most cases were for
      nonfunctioning kidneys and renal cell carcinoma, with transitional cell carcinoma
      and stones forming a smaller proportion. Over the 3 years, the mean (range)
      operative duration has reduced from 173 (89-335) to 166 (42-395) min. The median
      postoperative stay remained at 4-5 days, with a wide range reflecting other than
      clinical reasons for delayed discharge. The mortality rate remained low, at 0.7%
      and 0.2%, respectively, for 2002 and 2004. The mean conversion rate remained at 6
      8% and the mean complication rate at 17-2%, but the proportion of major
      complications reduced from 10% to 4%. The transfusion rate also reduced from 10%
      to 7%. The operative duration, transfusion and conversion rates were higher in
      those centres performing fewer than 12 cases/year than in those performing at
      least one case per month. CONCLUSION: The BAUS laparoscopic nephrectomy audit is
      an effective method for ensuring both the safe and widespread implementation of
      this relatively new technique to the UK, and compliance with internationally
      accepted standards. This audit has shown differences in clinical outcomes in
      favour of high-volume centres, which may help to inform decisions about the
      centralization of urological laparoscopy services.

PMID- 16430643
TI  - Current concepts in achieving renal hypothermia during laparoscopic partial
      nephrectomy.

PMID- 16430642
TI  - The epidemiology of trauma of the genitourinary system after traffic accidents:
      analysis of a register of over 43,000 victims.
AB  - OBJECTIVE: To analyse the frequency and type of injury to the genitourinary
      system, by user category, after traffic accidents. PATIENTS AND METHODS: The
      register which forms the basis of this study is unique in Europe and includes
      43,056 victims of road traffic accidents, and was compiled between 1996 and 2001.
      The categories of road users included: motorists, motorcyclists, cyclists,
      pedestrians, van and bus users, and roller skaters. The urological complication
      rate was analysed for each category. RESULTS: In all, 199 cases of trauma of the
      genitourinary system (0.46%) were recorded. The most frequent urological
      complications were renal (43%) and testicular trauma (24%), the former most
      frequent in motorists (65%) and pedestrians (29%), and the latter in
      motorcyclists (41%). CONCLUSIONS: An analysis of this register provides better
      knowledge of the urogenital injuries after traffic accidents. Renal and
      testicular injuries are the most frequent.

PMID- 16430644
TI  - Histopathological evaluation of the uterosacral ligament: is this a dependable
      structure for pelvic reconstruction?
AB  - OBJECTIVE: To explore, by histological examination, whether the uterosacral
      ligament complex is an adequate support structure for vaginal vault suspension
      and other reconstructive procedures of the female pelvis. MATERIALS AND METHODS:
      We dissected 14 fresh hemipelves from seven adult female cadavers. The
      uterosacral complexes were excised from the pelvic sidewall immediately beneath
      the uterosacral pedicle. The specimens were stained with connective tissue
      specific Movat stain and evaluated microscopically for the presence of collagen
      and/or elastin. RESULTS: Uterosacral tissue similar to that identified during
      pelvic reconstructive surgery was obtained in all cases. Six of the women had had
      a hysterectomy. A ligamentous structure with clearly aligned collagen and
      interspersed elastin was identified in only three specimens, two from one cadaver
      of a young woman who had not had a hysterectomy. The other specimens had an
      attenuated, poorly organized layer of collagen immediately beneath the
      peritoneum. CONCLUSION: We could not consistently identify normal ligamentous
      tissue in the uterosacral complexes. The overwhelming majority of specimens from
      women who had had a hysterectomy showed disorganized tissue with reduced
      cellularity. This reinforces doubts about the integrity of these tissues as
      structural supports in pelvic reconstructive surgery, particularly in elderly
      women who have had a hysterectomy.

PMID- 16430645
TI  - Gender-associated differences in the psychosocial and developmental outcome in
      patients affected with the bladder exstrophy-epispadias complex.
AB  - OBJECTIVE: To identify problems in the long-term psychosocial and developmental
      outcome specific to patients with the bladder exstrophy-epispadias complex
      (BEEC), using a self-developed semi-structured questionnaire, as there are
      various techniques of reconstruction to repair BEEC but to date neither patients
      nor surgeons have a clear answer about which type gives the most acceptable long
      term results. PATIENTS AND METHODS: Increasingly many patients with BEEC reach
      adulthood and wish to have sexual relationships and families. To date, no studies
      have used disease-specific psychological instruments to measure the psychosocial
      status of patients with BEEC. Thus we contacted 208 patients with BEEC, and 122
      were enrolled, covering the complete spectrum of the BEEC. The data assessed
      included the surgical reconstruction, subjective assessment of continence,
      developmental milestones, school performance and career, overall satisfaction in
      life, disease-specific fears and partnership experiences in patients aged >18
      years. We compared affected females and males to assess gender-associated
      differences in quality of life. RESULTS: Affected females had more close
      friendships, fewer disadvantages in relation to healthy female peers and more
      partnerships than the males. Family planning seemed to be less of a problem in
      affected females. There were no gender differences in the adjustments within
      school and professional career, which was very good in general. CONCLUSION:
      Future studies are needed to assess the disease-specific anxieties, considering
      gender-specific differences.

PMID- 16430646
TI  - Urodynamic effects of propiverine hydrochloride in children with neurogenic
      detrusor overactivity: a prospective analysis.
AB  - OBJECTIVES: To evaluate prospectively the efficacy and tolerability of
      propiverine for treating neurogenic detrusor overactivity (NDO) in children.
      PATIENTS AND METHODS: Twenty children (mean age 8.9 years; median 5.6) with NDO
      due to an upper motor neurone lesion were enrolled (17 had myelomeningocele). In
      the urodynamic examination, reflex volume (RV), maximum detrusor pressure (MDP),
      maximum cystometric bladder capacity (MCBC) and bladder compliance (BC) before
      and after a twice-daily propiverine hydrochloride regimen were determined. The
      urodynamic follow-up was after 3-6 months. Incontinence was assessed by an
      incontinence score. RESULTS: The mean (sem) RV increased from 103.8 (21.3) to
      174.5 (33.7) mL (P < 0.005), MDP decreased from 52.5 (7.9) to 40.1 (6.2) cmH(2)O
      (P < 0.05), MCBC increased from 166 (28.8) to 231.9 (34.8) mL (P < 0.005), and BC
      improved from 11.2 (2.8) to 30.6 (9.7) mL/cmH(2)O (P < 0.01), with propiverine
      treatment. The incontinence score (scale 0-3) improved from 2.4 (0.2) to 1.6
      (0.3) (P < 0.05). Propiverine was well tolerated, although some children were
      given higher doses than recommended. CONCLUSIONS: Propiverine hydrochloride is
      effective and well tolerated in the treatment of children with NDO. Because of
      its dual mode of action, it is well tolerated even in children who need higher
      doses. Propiverine hydrochloride is a preferable alternative to oxybutynin, the
      anticholinergic most frequently used in children with NDO to date.

PMID- 16430647
TI  - Paediatric percutaneous nephrolithotomy: setting new frontiers.
AB  - OBJECTIVE: To assess the safety and outcome of paediatric percutaneous
      nephrolithotomy (PCNL) for atypical cases and compare the results with 'standard'
      unilateral paediatric PCNL. PATIENTS AND METHODS: We retrospectively reviewed
      children who had had a PCNL between December 1997 and December 2004. Patients
      were grouped as follows: group 1, aged >5-16 years with normal anatomy and normal
      renal function undergoing unilateral PCNL or staged bilateral PCNL; group 2, < or
      = 5 years with normal anatomy and renal function undergoing unilateral PCNL;
      group 3, undergoing bilateral simultaneous PCNL; group 4, impaired renal function
      in addition to renal stone disease; group 5, renal anatomical abnormality with
      calculi in the same kidney. Demographics, stone profile, procedure and outcome
      indicators were analysed for each group. RESULTS: In all, 188 consecutive PCNLs
      in 169 children were included (mean age 3.3-10.3 years, mean stone burden 19.1
      33.3 mm in the five groups). The mean duration of PCNL was 69-115 min. Stone
      clearance was satisfactory with single tract access in 90-100% of patients.
      Transient postoperative fever was the commonest complication (12.5-51%) followed
      by hyponatraemia and hypokalaemia. Blood transfusion was required in 0-7.7%. The
      mean stone clearance rates were 47-90% in the five groups; additional
      extracorporeal shockwave lithotripsy increased the cumulative clearance rates to
      90-100%. CONCLUSION: PCNL is safe for treating renal stones, with excellent
      results and minimal complications. Comparable results are achieved in the very
      young child, children with anatomically abnormal kidneys, children with impaired
      renal function and children with bilateral renal stones undergoing simultaneous
      bilateral PCNL. Hence none of these factors should be considered as relative
      contraindications.

PMID- 16430650
TI  - Alterations in purinergic and cholinergic components of contractile responses of
      isolated detrusor contraction in a rat model of partial bladder outlet
      obstruction.
AB  - OBJECTIVE: To study the effect of 3 weeks of partial bladder outlet obstruction
      (BOO), compared to a sham operation, on the cholinergic and purinergic components
      of detrusor contractile responses to agonists and to electrical field stimulation
      (EFS); the expression of P2X receptor subtypes was also examined. MATERIALS AND
      METHODS: Partial BOO was induced in female Sprague-Dawley rats by surgically
      applying a jeweller's silver 'jump' ring around the urethra, such that the
      urethra was constricted but not closed. Sham-operated female rats underwent an
      identical procedure without placement of a ring. RESULTS: After 3 weeks of
      partial BOO the rat bladders became significantly hypertrophied, doubling in
      weight. Spontaneous activity was markedly increased, but the contractile response
      to a single bolus of KCl (120 mM) was unaltered. The neurogenic-induced
      contractile responses of strips of detrusor from obstructed bladders were
      significantly greater than those from sham-operated bladders, and the responses
      of strips of detrusor from obstructed bladders to EFS showed a significantly
      greater atropine-sensitive component than sham-operated detrusor. However, the
      response of detrusor strips to EFS that was susceptible to desensitization by
      alpha,beta-methylene ATP was not significantly changed in obstructed bladders.
      The sensitivity of the strips from obstructed bladders to carbachol, ATP and
      beta,gamma-methylene ATP was less than in sham-operated detrusor.
      Immunohistochemical studies showed no difference in the P2X receptor subtypes
      expressed on detrusor smooth muscle from obstructed and sham-operated rats.
      CONCLUSION: In the rat, after moderate bladder hypertrophy, the atropine
      sensitive component was significantly up-regulated, but the ATP-sensitive
      component was marginally reduced, although not significantly. These results
      suggest that up-regulation of the P2X component of bladder contraction seen in
      humans with bladder instability, and in other species models of BOO, is not
      mirrored in the rat, or occurs later in the pathological process of bladder
      hypertrophy.

PMID- 16430649
TI  - Late urodynamic findings after treating traumatic rupture of the posterior
      urethra in boys.
AB  - OBJECTIVE: To investigate lower urinary tract (LUT) functions in a prospective
      study in boys treated for posterior urethral distraction (PUD), as posterior
      urethral stricture, erectile dysfunction and incontinence can occur after various
      treatments for this rare injury in children. PATIENTS AND METHODS: Eleven boys
      were treated for PUD and resultant stricture between 1980 and 2000. Their age,
      the cause of trauma, extent of injury, previous treatment, and continence status
      were evaluated, and a urodynamic study conducted. Controls were 12 age-matched
      males who underwent similar cystometrography (CMG) and uroflowmetry. RESULTS: The
      mean (SD) age at injury was 8 (4) years and the cause was traffic accident in
      nine and crush injury in two boys. Seven boys had an isolated urethral rupture,
      two also had a bladder neck injury and two also had a perforated bladder. No
      gross neurological impairment developed after trauma. Voiding cysto-urethrograms
      after initial therapy showed vesico-ureteric reflux in five boys, but in only one
      at the time of the urodynamic studies. At the time of urodynamic study, the mean
      (SD) age of the patients was 15 (6) years; seven were fully continent, one had
      intermittent leakage, two were incontinent, and one had nocturnal enuresis. CMG
      electromyography (EMG) showed a reduced maximum cystometric capacity in nine
      patients, reduced compliance in 10, stable detrusor in 11, synergic detrusor
      sphincter activity in 11, and residual urine in one. The uroflowmetry-EMG study
      showed prolonged voiding time and flow time, decreased maximum flow urinary rate
      (Q(max)) and mean flow rate (Q(avg)). The shape of the flow curve showed an
      uninterrupted low-amplitude pattern. Comparing these patients with age-matched
      controls, CMG and uroflowmetry studies showed that the maximum cystometric
      bladder capacity, compliance, Q(max) and Q(avg) were all significantly lower in
      patients with PUD, while voiding time and flow time were significantly higher.
      CONCLUSION: The LUT deteriorates after treating PUD in boys. CMG and uroflowmetry
      findings are consistent with partial anatomical obstruction distal to the
      bladder. Our results are preliminary and full urodynamics, including pressure
      flow studies, will be useful to support this conclusion. A urodynamic study
      should be integral in the management of PUD.

PMID- 16430648
TI  - Re-exploration of the acute scrotum.
AB  - OBJECTIVE: To investigate children and adolescents who had scrotal exploration
      more than once. PATIENTS AND METHODS: Between 1994 and 2004, 64 of 840 (7.6%)
      boys had more than one scrotal exploration at our institution. The age,
      laterality of the explorations, the interval between and findings at operation,
      whether the testes were managed by orchidopexy and how, and the complications,
      were reviewed from the medical records and the operating reports of the patients.
      All the boys were followed at the outpatient clinic 2-4 weeks after surgery.
      RESULTS: The median (range) age of the patients was 11.5 (2-15) years; 61 had two
      scrotal explorations and three were explored three times. Of the patients, 32
      presented with right testicular pain, 31 had left pain, and one had bilateral
      testicular pain. In the second exploration, 56 of 64 had the contralateral testis
      explored, five had an ipsilateral exploration and three had bilateral
      exploration. Forty-eight of the 64 boys (70%) had torsion of the contralateral
      appendix testis at the second exploration, and 5.3% (45/840) of the total number
      of children operated for acute scrotum had metachronous torsion of the appendix
      testis. The median interval between the first and second exploration was 8 months
      (1 day to 10.5 years). Two boys had three scrotal explorations, and three of 64
      (4.7%) boys developed complications that required re-exploration. CONCLUSIONS:
      Most indications for recurrent scrotal exploration in this study are because of a
      twisted contralateral appendix testis, but the risk of developing this pathology
      is similar to the complication rate of repeat scrotal exploration. These data
      support our policy that the contralateral testis should not be routinely explored
      nor its appendix removed unless there is ipsilateral testicular torsion.

PMID- 16430651
TI  - Interstitial cells and cholinergic signalling in the outer muscle layers of the
      guinea-pig bladder.
AB  - OBJECTIVES: To explore the relationship between cholinergic mechanisms and
      interstitial cells (ICs) in the outer muscle layer of the bladder. MATERIALS AND
      METHODS: In bladder tissue from male guinea-pigs, ICs were identified by their
      response to nitric oxide (NO) with a rise in cGMP. Sections of the lateral
      bladder wall were incubated in Krebs' solution containing 1 mm of the nonspecific
      phosphodiesterase inhibitor isobutyl-methyl-xanthene. Tissues were then exposed
      to 100 microm of the NO donor NONOate for 10 min, control tissues remained in
      Krebs' solution. Tissues were then processed for immunohistochemistry for cGMP,
      choline acetyltransferase (ChAT), neurofilament protein, and the nonspecific
      neuronal marker protein gene product (PGP) 9.5. RESULTS: cGMP-positive ICs were
      found mainly in the outer muscle layers of the bladder wall. Three types were
      identified based on location; on the outer surface of the bladder wall, on the
      surface of the muscle bundles, and within the muscle bundles. Some of the
      intramuscular ICs stained for ChAT, but they did not stain with PGP 9.5. Nerve
      fibres were seen in close contact with the ChAT-positive intramuscular ICs, and
      these nerves expressed ChAT and neurofilament protein. CONCLUSIONS: A
      subpopulation of intramuscular ICs can synthesise acetylcholine, and might
      release acetylcholine onto the underlying muscle. These cells are in close
      contact with nerves, suggesting that they might be activated by neural inputs.
      Thus there may be a system in the detrusor involving cholinergic nerves acting on
      ICs which can activate the smooth muscle via a complex cholinergic input.

PMID- 16430652
TI  - L6-S1 spinal nerve stimulation reduces micturition frequency in anaesthetized
      rats with cyclophosphamide-induced cystitis.
AB  - OBJECTIVE: To further investigate the rationale for using spinal nerve
      stimulation (SNS) for treating bladder overactivity associated with cystitis in a
      rat model of cyclophosphamide-induced cystitis, as several studies suggested that
      symptoms associated with chronic cystitis could be treated using stimulation of
      sacral spinal nerves, but the mechanisms by which it works are unknown. MATERIALS
      AND METHODS: Cystitis was induced by i.p. injection of cyclophosphamide 48 h
      before the experiments in anaesthetized male rats. Neurograms were taken by
      placing a recording electrode onto the pelvic nerve and a stimulating electrode
      on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were
      then evaluated for SNS in control and cyclophosphamide-treated rats during
      cystometry. RESULTS: Cyclophosphamide resulted in significant bladder
      overactivity. There was no apparent difference in the neurograms generated in
      response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and
      control rats. Intensities of 200 microA (Adelta-fibre-specific) and 2 mA (Adelta+
      C-fibres) were chosen for SNS. Continuous SNS at 200 microA significantly reduced
      the frequency of voiding and non-voiding contractions in cyclophosphamide-treated
      rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied
      by continuous leakage of urine. CONCLUSION: SNS recruiting only Adelta-fibre
      produced fewer voiding contractions in cyclophosphamide-treated rats, to a level
      similar to that from the control rats. These results support the ability of SNS
      to decrease bladder overactivity in a pathophysiological model of chemical
      irritation of the bladder.

PMID- 16430653
TI  - Distribution of neuropeptide Y-containing nerves in the neurogenic and non
      neurogenic detrusor.
AB  - OBJECTIVE: To evaluate the role of neuropeptide Y in the detrusor of patients
      with neurogenic detrusor overactivity (NDO), as it has an important role in the
      neural regulation of the lower urinary tract by exerting differential effects on
      the release of cholinergic and adrenergic transmitters via autoinhibition and
      heterosynaptic interactions. MATERIALS AND METHODS: Detrusor biopsies were
      obtained from 38 patients; 31 had video-urodynamically verified NDO, caused by
      meningomyelocele in 17 or spinal cord injury in 14. Seven had stress urinary
      incontinence (SUI) and this group served as a control. All specimens were fixed,
      paraffin wax-embedded, sectioned and stained with a monoclonal antibody against
      neuropeptide Y and a general nerve marker protein-gene-product 9.5 (PGP 9.5). The
      number of PGP 9.5- and neuropeptide Y-containing nerves was quantified by a
      standardized evaluation using image-analysis software. RESULTS: The median
      (range) number of neuropeptide Y-containing nerves in the neurogenic detrusor, at
      0.273 (0.126-0.639) per muscle cell nucleus (MCN), was significantly lower (P =
      0.014) than that in patients with SUI, at 0.383 (0.267-0.728). In the neurogenic
      detrusor the number of PGP 9.5-positive nerves, at 0.278 (0.054-0.641)/MCN was
      also lower (P = 0.111) than in patients with SUI, at 0.368 (0.258-0.497). The
      ratio of neuropeptide Y to PGP 9.5 counts per biopsy did not differ between the
      groups (P = 0.628). CONCLUSIONS: The number of PGP 9.5-positive nerves was not
      significantly and the number of neuropeptide Y-containing nerves was
      significantly reduced in patients with NDO. This may have been caused by
      transynaptic nerve degeneration of the detrusor, as described by in patients with
      spinal cord injury. As neuropeptide Y inhibits the contractile response of the
      detrusor the reduction of neuropeptide Y-containing nerves may play a role in the
      development and persistence of DO.

PMID- 16430654
TI  - Intravesical instillation of human urine after oral administration of trospium,
      tolterodine and oxybutynin in a rat model of detrusor overactivity.
AB  - OBJECTIVE: To study the effects of antimuscarinics excreted into human urine on
      normal bladder in a rat model of detrusor overactivity. MATERIALS AND METHODS:
      Two 'normal' adult volunteers collected voided urine after taking trospium (20
      mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10
      mg, four times daily). The drugs were taken in a random order for 5 days with a 7
      day washout period between the drugs. The urine collected from the two volunteers
      was mixed together and then blindly labelled and used for testing. Control human
      urine (no oral antimuscarinics) was also used. The effect of intravesical
      administration of human urine on carbachol-induced bladder overactivity was
      studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric
      variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human
      urine, then a mixture of carbachol (30 microm) and human urine were compared in
      the four groups (control and the three different antimuscarinics tested; six rats
      per group). RESULTS: Human urine, with or with no intake of antimuscarinic
      agents, had no effect on normal bladder function. Bladder capacity and
      intercontraction intervals were significantly decreased after adding carbachol to
      urine containing vehicle, tolterodine or oxybutynin. However, urine collected
      from the humans who had taken trospium prevented the carbachol-induced reduction
      in bladder capacity and intercontraction intervals. Maximum voiding pressure and
      pressure threshold were not changed in any case. CONCLUSION: This is the first
      report that the urine excreted after oral ingestion of trospium (20 mg, twice
      daily) has a significant inhibitory effect in a rat model of detrusor
      overactivity. This suggests that antimuscarinic agents have a local bladder
      effect during the bladder-storage phase in addition to the smooth muscle-mediated
      voiding phase.

PMID- 16430655
TI  - Amplification of the urokinase gene and the sensitivity of prostate cancer cells
      to urokinase inhibitors.
AB  - OBJECTIVES: To evaluate the frequency of the urokinase-type plasminogen activator
      (uPA) gene amplification and the sensitivity of prostate cancer cells to uPA
      inhibition, as we previously found one hormone-refractory prostate tumour with
      high-level amplification of the uPA (alias PLAU) gene, and also showed that a uPA
      inhibitor, amiloride, can effectively reduce the invasion potential of the PC-3
      prostate cancer cell line. MATERIALS AND METHODS: Sixty-three locally recurrent
      hormone-refractory tumours and 78 hormone-refractory metastases from 29 patients
      who died from prostate cancer were analysed for uPA gene-copy number using
      fluorescence in situ hybridization. The Matrigel invasion assay was used to study
      the influence of uPA inhibitors on the invasive potential of prostate cancer cell
      lines. RESULTS: Of the locally recurrent hormone-refractory tumours, 21% had an
      increased copy number of uPA, but no high-level amplifications were found; 31% of
      the metastases had increased copy number and one high-level amplification of the
      uPA. Matrigel invasion assays with two specific uPA inhibitors, B428 and p
      aminobenzamidine, showed that invasion of a prostate cancer cell line containing
      uPA gene amplification was inhibited by these small-molecule uPA inhibitors,
      while invasion of prostate cell lines without uPA gene amplification were not.
      CONCLUSION: These results suggest that selective inhibition of the uPA pathway in
      individuals whose tumours contain uPA gene amplification may provide therapeutic
      benefit.

PMID- 16430656
TI  - Left to our own devices.

PMID- 16430657
TI  - A prospective study to evaluate the safety, tolerability, efficacy and durability
      of response of intravesical injection of botulinum toxin type A into detrusor
      muscle in patients with refractory idiopathic detrusor overactivity.

PMID- 16430658
TI  - Urine cytology after flexible cystoscopy.

PMID- 16430659
TI  - Cystoscopic removal of a JJ stent using a suture 'lasso'.

PMID- 16430660
TI  - What surgical resection margins are required to achieve oncological control in
      men with primary penile cancer?

PMID- 16430661
TI  - Radical prostatectomy versus watchful waiting.

PMID- 16430663
TI  - Colonic pouch (Mainz-pouch III) for continent urinary diversion.

PMID- 16430664
TI  - Malaria and blood transfusion.
AB  - The transmission of malaria by blood transfusion was one of the first recorded
      incidents of transfusion-transmitted infection. Although a number of different
      infections have been reported to be transmitted by transfusion since then, on a
      global scale malaria remains one of the most common transfusion-transmitted
      infections. Transfusion-transmitted malaria can have serious consequences, as
      infection with Plasmodium falciparum may prove rapidly fatal. Ensuring that, in
      non-endemic countries, the blood supply is free from malaria is problematical,
      especially as travel to malarious areas is increasing and there is some spread of
      the disease into new areas, as well as a resurgence of malaria in areas where
      previously it had been eradicated. In non-endemic countries, donor deferral can
      be effective, but clear guidelines are needed. In endemic countries the problem
      is far greater as the majority of donors may be potentially infected with malaria
      parasites. In both situations, the simple deferral of donors may be wasteful and
      can eventually erode the donor base. Thus, other strategies are needed to ensure
      safety with sufficiency. However, the screening of donations for evidence of
      malaria is not without its problems. Although the examination of blood films is
      still the basis for diagnosing acute malaria, in most situations it is not
      sufficiently sensitive for blood bank screening. In non-endemic countries, donor
      deferral in combination with screening for specific antimalarial immunoglobulin
      provides an effective means of minimizing the risk of transmission. In endemic
      countries, more specific donor questioning, consideration of seasonal variation
      and geographical distribution may help to identify the population of donors who
      are most likely to be infected. In addition, the administration of antimalarials
      to transfusion recipients may help to prevent transmission. Nonetheless, no
      matter what strategy is adopted, it is likely that cases of transfusion
      transmitted malaria may still occur, so malaria must always be considered in any
      patient with a febrile illness post-transfusion.

PMID- 16430665
TI  - Pathogen inactivation of Leishmania donovani infantum in plasma and platelet
      concentrates using riboflavin and ultraviolet light.
AB  - BACKGROUND AND OBJECTIVES: Leishmania is transmitted by the bite of the
      phlebotomine sandfly or by transfusion of infected blood products. Leishmaniasis
      currently poses a significant problem in several parts of the world, and is an
      emerging problem in others. The Mirasol PRT technology is based on the use of
      riboflavin and ultraviolet light to generate chemical reactions in the nucleic
      acids of pathogens, which prevents replication and leads to inactivation. The
      intent of this study was to examine the ability of the Mirasol PRT System to kill
      the Leishmania parasite in human plasma and platelet concentrates. MATERIALS AND
      METHODS: In visceral Leishmaniasis, amastigotes are present in the blood and in
      the reticuloendothelial system within monocytes. For each unit of plasma or
      platelets treated, isolated mononuclear cells obtained from 100 ml of normal
      donor whole blood were incubated with 1.0 x 10(8) Leishmania donovani infantum
      promastigotes to produce amastigote-laden macrophages. The infected macrophages
      were added to 250 ml of human plasma or to 250 ml of platelet concentrates.
      Infected units were cultured pretreatment in 10-fold serial dilutions to
      determine the limits of detection. Thirty millilitres of 500 microM riboflavin
      was added to each unit, which was then illuminated with 5.9 J/cm2 of ultraviolet
      light (6.24 J/ml). After treatment and after 2 months of frozen storage, plasma
      units were cultured in 10-fold serial dilutions. Platelets were cultured on the
      day of treatment and on day 5 of storage post-illumination. RESULTS: A 5 log
      reduction of Leishmania was demonstrated in five of six units of plasma, and a 7
      log reduction of Leishmania was demonstrated in one plasma unit. A 5 log
      reduction of Leishmania was demonstrated in five of six units of platelets, and a
      6 log reduction of Leishmania was demonstrated in one unit. CONCLUSIONS: There is
      no donor screen for Leishmania and other pathogens constantly emerging in our
      blood supply. The Mirasol PRT System for Platelets and Plasma is an effective
      means of killing Leishmania and other emerging pathogens in these blood products.

PMID- 16430666
TI  - Collection of hyperconcentrated platelets with Trima Accel.
AB  - BACKGROUND AND OBJECTIVES: Lowering the plasma content in single-donor platelet
      (PLT) concentrates well below 30% implies the need to collect platelets at very
      high concentrations. Trima Accel (TA) is validated for collection below 4000 x
      10(3) PLTs/microl. We evaluated its performance at 5000 x 10(3) PLTs/microl.
      MATERIALS AND METHODS: Twenty blood donors underwent apheresis with TA twice
      collecting either a hyperconcentrated or a standard single-donor platelet
      concentrate with a target platelet concentration of 5000 or 1200 x 10(3)
      PLTs/microl, respectively. We analysed the collection efficiency, the collection
      rate and the quality of the collected by-plasma. RESULTS: We collected 20
      hyperconcentrated and 20 standard units containing 2.56 +/- 0.5 and 3.39 +/- 0.4
      x 10(11) PLTs at a concentration of 4518 +/- 978 and 1374 +/- 166 x 10(3)
      PLTs/microl in 45 +/- 8 and 39 +/- 6 min resulting in a collection efficiency of
      47.5 +/- 10.0 and 70.7 +/- 7.9% and a collection rate of 5.9 +/- 1.4 and 8.8 +/-
      1.5 x 10(9) PLTs/min, respectively (all results expressed as mean +/- standard
      deviation). The collected by-plasma showed a very high grade of cell purity and a
      satisfactory recovery of the clotting factors. CONCLUSION: Although TA is a
      suitable device for PLT collection at very high concentrations, improvements are
      desirable to further increase the productivity above its currently validated
      upper collect concentration limit.

PMID- 16430667
TI  - A modified caprylic acid method for manufacturing immunoglobulin G from human
      plasma with high yield and efficient virus clearance.
AB  - BACKGROUND AND OBJECTIVES: The increasing demand for intravenous immunoglobulin
      (IVIG) necessitates the development of improved plasma fractionation methods,
      providing higher immunoglobulin G (IgG) recovery. Here, we describe a new IVIG
      production process resulting in a high yield of IgG and effective reduction of
      physico-chemically resistant viruses. MATERIALS AND METHODS: IgG was purified
      from Cohn fraction II+III by caprylic acid treatment, polyethylene glycol
      precipitation, anion-exchange chromatography, nanofiltration and ultrafiltration.
      Stability of the purified IgG was studied in different formulations. Virus
      reduction was studied with two viruses: bovine viral diarrhoea virus, assessed by
      an infectivity assay; and human parvovirus B19, assessed by polymerase chain
      reaction. RESULTS: The combination of caprylic acid treatment with polyethylene
      glycol precipitation and a single anion-exchange chromatography yielded polymer
      free, pure IgG. The purified IgG could be filtered through a small pore-size
      virus filter (Millipore V-NFP) with high throughput and excellent yield. The
      formulated product was stable as a 100 g/l IgG solution. Bovine viral diarrhoea
      virus was effectively inactivated by the caprylic acid treatment, and parvovirus
      B19 was effectively removed in the polyethylene glycol precipitation and
      nanofiltration stages, the total reduction of parvovirus being approximately 14
      log10. CONCLUSIONS: The new process gives pure and stable IgG solution with an
      average yield of 4.8 g of IgG per kg of recovered plasma and has a very high
      capacity to remove even physico-chemically resistant viruses.

PMID- 16430668
TI  - Silent myocardial ischaemia and haemoglobin concentration: a randomized
      controlled trial of transfusion strategy in lower limb arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: Red cell transfusion is commonly used in orthopaedic
      surgery. Evidence suggests that a restrictive transfusion strategy may be safe
      for most patients. However, concern has been raised over the risks of anaemia in
      those with ischaemic cardiac disease. Perioperative silent myocardial ischaemia
      (SMI) has a relatively high incidence in the elderly population undergoing
      elective surgery. This study used Holter monitoring to compare the effect of a
      restrictive and a liberal red cell transfusion strategy on the incidence of SMI
      in patients without signs or symptoms of ischaemic heart disease who were
      undergoing lower limb arthroplasty. MATERIALS AND METHODS: We performed a
      multicentre, controlled trial in which 260 patients undergoing elective hip and
      knee replacement surgery were enrolled and randomized to transfusion triggers
      that were either restrictive (8 g/dl) or liberal (10 g/dl). Participants were
      monitored with continuous ambulatory electrocardiogram (ECG) (Holter monitoring),
      preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for
      new ischaemia by technicians blinded to treatment. The total ischaemia time in
      minutes was divided by the recording time in hours and an ischaemic load in min/h
      was calculated. Haemoglobin levels were measured preoperatively, postoperatively
      in the recovery room, and on days one, three and five after surgery. RESULTS: The
      mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive
      group and 11.09 g/dl in the liberal group. In the restrictive group, 34% were
      transfused a total of 89 red cell units, and in the liberal group 43% were given
      a total of 119 red cell units. A postoperative episode of silent ischaemia was
      experienced by 21/109 (19%) patients in the restrictive group and by 26/109 (24%)
      patients in the liberal group [mean difference -4.6%; 95% confidence interval
      (CI): -15.5% to 6%, P = 0.41). There was no significant difference (P = 0.53)
      between the overall ischaemic load in the restrictive group (median 0 min/h,
      range 0-4.18) and the liberal group (median 0 min/h, range 0-19.48). In those
      patients who did experience postoperative SMI, the mean ischaemic load was 0.48
      min/h in the restrictive group and 1.51 min/h in the liberal group (ratio 0.32,
      95% CI: 0.14-0.76, P = 0.011). The median postoperative length of hospital stay
      in the restrictive group was 7.3 days [range 5-11; interquartile range (IQR) 6-8]
      compared with 7.5 days (range 5-13; IQR 7-8) in the liberal group. The numbers
      were not large enough to conclude equivalence. CONCLUSIONS: In patients without
      preoperative evidence of myocardial ischaemia undergoing elective hip and knee
      replacement surgery, a restrictive transfusion strategy seems unlikely to be
      associated with an increased incidence of SMI. A proportion of these patients
      experience moderate SMI, regardless of the transfusion trigger. Use of a
      restrictive transfusion strategy did not increase length of hospital stay, and
      use of this strategy would lead to a significant reduction in red cell
      transfusion in orthopaedic surgery. Our data did not indicate any potential for
      harm in employing such a strategy in patients with no prior evidence of cardiac
      ischaemia who were undergoing elective orthopaedic surgery.

PMID- 16430669
TI  - An investigation of the impact of prolonged waiting times on blood donors in
      Ireland.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the impact of
      prolonged queuing times on blood donors, by measuring their satisfaction levels,
      and positive and negative affects. As donation times have increased over the past
      number of years within the Irish Blood Transfusion Service, this is an important
      issue to examine in a climate where voluntary donors are becoming scarce and
      demands on people's time are increasing. MATERIALS AND METHODS: Eighty-five blood
      donors were sampled from one urban and one rural blood donor clinic. The
      respondents conducted a questionnaire by means of face-to-face interview, while
      waiting in the clinic. The questionnaire contained the Positive and Negative
      Affect Scale (PANAS), and a waiting satisfaction scale. Both actual and perceived
      waiting times of the donors were noted. RESULTS: Waiting time was found to be
      negatively related to satisfaction. Inexperienced donors expressed higher levels
      of negative affect than experienced donors. Urban donors were significantly more
      satisfied than rural donors. There was a significant difference in perceived
      waiting time between lone donors and those queuing in a group, with those waiting
      alone perceiving their wait as shorter. While all respondents stated that they
      intended to donate again, over one-third stated that prolonged waiting times
      would be their most likely deterrent. However, only 15% stated that long queuing
      times might actually prevent them from donating in the future, and almost all
      respondents said that they would recommend donation to a friend, despite long
      queuing times. CONCLUSIONS: Although our results show that the respondents were
      not satisfied with current waiting times, it did not seem to affect their future
      intentions to donate. These findings provide some optimism for the future of
      blood donation in Ireland, as they suggest a strong sense of commitment to
      donation within the population sampled. Future research could explore the
      application of 'the service industry' approach to waiting times to blood donation
      clinics.

PMID- 16430670
TI  - Novel polymorphisms in exons 6 and 7 of A/B alleles detected by polymerase chain
      reaction-single strand conformation polymorphism.
AB  - BACKGROUND AND OBJECTIVES: The ABO blood group system is the most important blood
      group system in transfusion medicine. In addition to the major A, B and O
      alleles, many rare alleles have been defined. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and analysis by PCR sequence
      specific primers (SSP) are commonly conducted for genotyping but have the
      limitation of being unable to detect unknown substitution(s) in amplified DNA
      fragments, whereas PCR-single strand conformation polymorphism (SSCP) can be used
      for both. MATERIALS AND METHODS: Three-hundred unrelated blood donors of the AB
      phenotype were enrolled. Four pairs of primers were designed to constitute two
      sets of multiplex PCRs: this amplifies four fragments spanning the entire exon 6
      and its immediate flanking regions, nucleotides 432-1065, as well as the 3'
      untranslated region of exon 7 of the ABO gene. The SSCP electrophoresis was
      carried out on a 12.5% polyacrylamide gel in a GenePhor electrophoresis unit. For
      those with unexpected banding patterns, SSCP analyses were performed in duplicate
      and samples were cloned and sequenced for exons 6 and 7. RESULTS: Seven samples
      were noted to have six variant alleles, of which five have not been previously
      reported in the literature. Of these five novel variants, four were derived from
      the B allele, while the other derived from the A allele. CONCLUSIONS: By using
      PCR-SSCP, five novel A/B alleles were found.

PMID- 16430671
TI  - In vitro evaluation of Haemonetics MCS+ apheresis platelet concentrates treated
      with photochemical pathogen inactivation following plasma volume reduction using
      the INTERCEPT Preparation Set.
AB  - Pathogen inactivation using the INTERCEPT Blood System requires platelet
      resuspension in InterSol and reduced plasma. Platelets in plasma collected on the
      Haemonetics MCS+ were processed on the INTERCEPT Preparation Set for plasma
      volume reduction and addition of InterSol. The use of the Preparation Set
      resulted in a mean platelet loss of 5.6 +/- 3.4%. Subsequent photochemical
      treatment (PCT) with amotosalen and ultraviolet A light, and 7 days of storage,
      resulted in acceptable changes for platelet swirling, lactate, lactate
      dehydrogenase (LDH), platelet factor-4 (PF4), p-selectin, glycoprotein V (GpV),
      pO2, pCO2, tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8). All
      platelet units processed with the Preparation Set and PCT met European
      requirements for leucoreduction and pH values.

PMID- 16430672
TI  - An International Standard for specifying the minimum potency of anti-D blood
      grouping reagents: evaluation of a candidate preparation in an international
      collaborative study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate a lyophilized
      monoclonal immunoglobulin M (IgM) anti-D preparation for use as an International
      Standard to specify a recommended minimum acceptable potency of anti-D blood
      grouping reagents. MATERIALS AND METHODS: The candidate International Standard
      (99/836) for specifying the minimum potency of anti-D blood-grouping reagents was
      evaluated against a wide range of commercial anti-D blood-grouping reagents in an
      international collaborative study involving 20 laboratories in 13 countries.
      Laboratories titrated reconstituted 99/836, in parallel with as many commercial
      anti-D blood-grouping reagents as were available to them, in tube tests according
      to specified haemagglutination methodology for low-protein (e.g. monoclonal IgM)
      and high-protein (e.g. polyclonal) reagents. The ratios of the mean end-point
      titres of the reagents to that of 99/836 within each laboratory were calculated.
      RESULTS: The ratios of the mean titres of the low-protein reagents to the mean
      titre of 99/836 within a laboratory fell between 0.25 and 2 for 43 of the 45 low
      protein anti-D reagents tested (i.e. the potencies of the low-protein reagents
      compared with 99/836 were between a 1:4 dilution of 99/836 to twice as potent as
      99/836). The ratios of the mean titres of the high-protein reagents to the mean
      titre of 99/836 within a laboratory fell within 0.125 and 1 for eight out of the
      10 high protein reagents tested. CONCLUSIONS: By international consensus, a 1:3
      dilution of reconstituted 99/836 was deemed appropriate to define a recommended
      minimum acceptable potency of low-protein anti-D blood-grouping reagents. A 1:8
      dilution of reconstituted 99/836 was deemed appropriate to define a recommended
      minimum acceptable potency of high-protein anti-D blood-grouping reagents. On the
      basis of the results presented here, 99/836 was established by the World Health
      Organization as the 1st International Standard for specifying the minimum potency
      of anti-D blood-grouping reagents, in tube tests.

PMID- 16430673
TI  - Sudden cardiac death associated with sports in young individuals: is screening
      the way to avoid it ?

PMID- 16430674
TI  - Susceptibility to infections in elite athletes: the S-curve.
AB  - The susceptibility to upper respiratory tract infections (URTIs) after physical
      exercise has been described with a J-shaped curve, suggesting protection from
      infections with moderate exercise and increased risk for URTI's in elite
      athletes. Several factors such as time of inoculation, previous infections,
      pathogen exposure, other stressors than exercise etc. can influence infection
      outcome. Observed infections in athletes can, therefore, be either the result of
      increased susceptibility to a novel pathogen, or more severe symptoms of an
      already established infection. Moreover, the definitions of "strenuous" exercise
      and "elite" athletes are equivocal, making comparisons between studies difficult.
      Because absence of infections is inevitable to become and maintain status as an
      elite athlete, it is suggested that there is an S-shaped relationship between
      exercise load and risk of infections. To become an elite athlete one has to
      possess state-of-the-art physique, including an immune system able to withstand
      infections even during severe physiological and psychological stress.

PMID- 16430675
TI  - Predictors of hamstring injury at the elite level of Australian football.
AB  - BACKGROUND: Hamstring injuries are the most common injury sustained by elite
      Australian football players and result in substantial costs because of missed
      training time, unavailability for matches and lost player payments. Evidence to
      support proposed risk factors for hamstring injury is generally lacking, limiting
      the development of appropriate prevention strategies. AIM: To identify intrinsic
      risk factors for hamstring injury at the elite level of Australian football.
      METHODS: A prospective cohort of 222 players underwent baseline measurement in
      the form of a self-report questionnaire and a musculo-skeletal screen during the
      pre-season period of the 2002 Australian football season. Injury surveillance and
      exposure data were collected for the full season. Logistic regression analyses
      were used to identify independent predictors of hamstring injury in this group of
      players. RESULTS: Thirty-one players sustained a hamstring injury. A past history
      (previous 12 months) of hamstring injury and increasing age were found to be
      independent predictors of hamstring injury. CONCLUSIONS: Older players and those
      with a previous history of hamstring injury are target groups for further
      research and implementation of injury prevention strategies. Restricted ankle
      dorsiflexion range of movement warrants consideration in the development of
      prevention programs for hamstring injury.

PMID- 16430676
TI  - Post-operative use of knee brace in bone-tendon-bone patellar tendon anterior
      cruciate ligament reconstruction: 5-year follow-up results of a randomized
      prospective study.
AB  - Sixty patients were prospectively randomized to brace and no-brace groups after
      bone-tendon-bone patellar tendon anterior cruciate ligament (ACL) reconstruction.
      The brace group wore a rehabilitation knee brace for 12 weeks post-operatively,
      while the no-brace group was mobilized immediately, and crutches were discarded 2
      weeks post-operatively. The groups were comparable with respect to age, gender,
      time from injury to surgery and concomitant injuries. There were no differences
      either pre-operatively or 5 years post-operatively (80% of patients reviewed)
      between the groups in terms of the knee score (Lysholm), activity level (Tegner),
      degree of laxity or isokinetic peak muscle torque. Thus it appears that knee
      braces are not needed in the post-operative rehabilitation after ACL
      reconstruction with the patellar tendon graft.

PMID- 16430677
TI  - The COL5A1 gene and Achilles tendon pathology.
AB  - PURPOSE: There is an increase in the incidence of Achilles tendon injuries as a
      result of the participation in physical activity. It has been suggested that some
      individuals have a genetic predisposition to Achilles tendon pathology (ATP). The
      aim of this study was to determine whether the alpha 1 type V collagen (COL5A1)
      gene, which encodes for a tendon protein, is associated with the symptoms of ATP.
      METHODS: One-hundred and eleven Caucasian subjects diagnosed with ATP and 129
      Caucasian control (CON) subjects were genotyped for the BstUI and DpnII
      restriction fragment length polymorphisms (RFLPs) within the COL5A1 gene.
      RESULTS: There was a significant difference in the allele frequencies of the
      COL5A1 BstUI RFLP between the ATP and CON subjects (P=0.006). The frequency of
      the A2 allele was significantly higher in the CON group (29.8%) than in the ATP
      group (18.0%) (odds ratio of 1.9; 95% confidence interval (CI) 1.3-3.0; P=0.004).
      This allele had a stronger protective role when only the 72 patients diagnosed
      with chronic Achilles tendinopathy were analyzed (odds ratio of 2.6; 95% CI 1.5
      4.5). CONCLUSIONS: The COL5A1 BstUI RFLP is associated with ATP and more
      specifically, chronic Achilles tendinopathy. Individuals with an A2 allele of
      this gene are less likely of developing symptoms of chronic Achilles
      tendinopathy.

PMID- 16430678
TI  - Predictive validity of ventilatory and lactate thresholds for cycling time trial
      performance.
AB  - PURPOSE: To determine which laboratory measurement best predicts 40 km cycling
      time-trial (TT) performance. METHODS: Fifteen male cyclists performed lactate
      threshold (LT), ventilatory-threshold (VT), 5 km and 40 km TT. Key variables of
      interest were Watts at thresholds. For VT determination we used: breakpoint of
      ventilatory equivalent of oxygen (VE/VO2); breakpoint of ventilatory equivalent
      of carbon dioxide (VE/VCO2); V-slope; respiratory exchange ratio (RER)=1 and
      0.95. For LT we used Stegmann's individual anaerobic threshold; the stage
      preceding the second 0.5 mmol L(-1) increase (Baldari); 4 mmol L(-1); 1 mmol L(
      1) increase in 3 min; the stage preceding the first 1 mmol L(-1) increase as
      criterion methods (<1 mmol). Analyses also included peak power during the
      incremental threshold tests (MaxVT(watts), MaxLT(watts)) and 5 km performance
      (5K(avgwatts)). RESULTS: Regression analyses between VT variables and
      40K(avgwatts) were significant for V-slope (r2=0.63), VE/VO2 (r2=0.64), RER(0.95)
      (r2=0.53), RER1 (r2=0.57), and MaxVT(watts) (r2=0.65). Regressions between LT
      variables and 40K(avgwatts) were significant for Baldari (r2=0.52), 4 mmol L(-1)
      (r2=0.36), <1 mmol (r2=0.35), Keul (r2=0.34), and MaxLT(watts) (r2=0.51).
      Regressions between 5K variables and 40K(avgwatts) were significant for
      5K(avgwatts) (r2=0.58). Paired t-tests between these variables and the
      40K(avgwatts) indicated that absolute power outputs at VE/VO2 (P=0.33), RER(0.95)
      (P=0.93), and 4 mmol L(-1) (P=0.39) were not significantly different from
      40K(avgwatts). CONCLUSION: We conclude that VT-based variables are generally
      superior to LT variables relative to predicting 40K(avgwatts), the simplest of
      several valid measures appears to be VE/VO2.

PMID- 16430679
TI  - Exercise performance in hypoxia after novel erythropoiesis stimulating protein
      treatment.
AB  - Maximal aerobic power at high altitude (<4000 m) does not increase with altitude
      acclimatization. In order to investigate the isolated effects of increased
      arterial oxygen content (CaO2) on maximal oxygen uptake (VO2max) in hypoxia, we
      studied 10 subjects during exercise in acute exposure to 12.6% O2 before and
      after novel erythropoiesis stimulating protein (NESP) induced increases in CaO2.
      Over a period of 1 month, weekly NESP treatment increased resting hemoglobin (Hb)
      from 13.8+/-0.9 to 16.2+/-0.5 g/dL, hematocrit from 42.1+/-0.6% to 49.0+/-1.5%,
      and CaO2 from 189.7+/-3.0 to 218.6+/-5.7 mL/L. At maximal exercise CaO2 was
      increased from 172.3+/-3.7 to 191.5+/-3.8 mL/L with NESP treatment, and although
      maximal heart rate was similar in both conditions (178.4+/-2.6 and 180.9+/-2.5
      b.p.m.) VO2max remained unaltered, the values being 3.12+/-2.0 and 3.12+/-2.0,
      before and after NESP treatment, respectively. NESP-injections in human subjects
      causes Hb and accordingly CaO2 to increase both in normoxia and hypoxia. Despite
      increases in CaO2 at maximal exercise in hypoxia VO2max is not increased.

PMID- 16430680
TI  - Research of stimulants and anabolic steroids in dietary supplements.
AB  - The purpose of this study was to analyze the composition of 103 dietary
      supplements bought on the internet. The supplements were dispatched in four
      different categories according to their announced contents [creatine,
      prohormones, "mental enhancers" and branched chain amino acids (BCAA)]. All the
      supplements were screened for the presence of stimulants and main anabolic
      steroids parent compounds. At the same time, the research was focused on the
      precursors and metabolites of testosterone and nandrolone. The study pointed out
      three products containing an anabolic steroid, metandienone, in a very high
      amount. The ingestion of such products induced a high quantity of metandienone
      metabolites in urines that would be considered as a positive antidoping test. The
      results have also shown that one creatine product and three "mental enhancers"
      contained traces of hormones or prohormones not claimed on the labels and 14
      prohormone products contained substances other than those indicated by the
      manufacturer. The oral intake of the creatine product revealed the presence of
      the two main nandrolone metabolites (19-norandrosterone and 19
      noretiocholanolone) in urine.

PMID- 16430681
TI  - Quantifying training intensity distribution in elite endurance athletes: is there
      evidence for an "optimal" distribution?
AB  - This study was designed to quantify the daily distribution of training intensity
      in a group of well-trained junior cross-country skiers and compare the results of
      three different methods of training intensity quantification. Eleven male
      athletes performed treadmill tests to exhaustion to determine heart rate and VO2
      corresponding to ventilatory thresholds (VT1, VT2), maximal oxygen consumption
      (VO2max), and maximal heart rate. VT1 and VT2 were used to delineate three
      intensity zones. During the same time period, all training sessions (N=384, 37
      strength training, 347 endurance) performed over 32 consecutive days were
      quantified using continuous heart rate registration and session Rating of
      Perceived Exertion (RPE). In addition, a subset of 60 consecutive training
      sessions was quantified using blood lactate measurements. Intensity distribution
      across endurance training sessions (n=318) was similar when based on heart rate
      analysis (75+/-3%, zone 1; 8+/-3%, zone 2; 17+/-4%, zone 3) or session RPE (76+/
      4%, zone 1; 6+/-5%, zone 2; 18+/-7%, zone 3). Similarly, from measurements of 60
      consecutive sessions, 71% were performed with <or=2.0 mM blood lactate, 7%
      between 2 and 4 mM, and 22% with over 4 mM (mean=9.5+/-2.8 mM). In this group of
      nationally competitive junior skiers, training was organized after a polarized
      pattern, with most sessions performed clearly below (about 75%) or with
      substantial periods above (15-20%) the lactate accommodation zone, which is
      bounded by VT1 and VT2. The pattern quantified here is similar to that reported
      in observational studies of elite endurance athletes across several sports. It
      appears that elite endurance athletes train surprisingly little at the lactate
      threshold intensity.

PMID- 16430682
TI  - A comparison between three rating scales for perceived exertion and two different
      work tests.
AB  - In the present article, three scales developed by Borg are compared on bicycle
      ergometer work. In the first study, comparing the Borg Ratings of Perceived
      Exertion (RPE) and Category scales with Ratio properties (CR10) scales, 40
      healthy subjects (12 men and eight women for each scale) with a mean age of about
      30 years (SD approximately 6) participated. A work-test protocol with step-wise
      increase of work loads every minute was used (20 W increase for men and 15 W for
      women). Ratings and heart rates (HRs) were recorded every minute and blood
      lactates every third minute. Data obtained with the RPE scale were described with
      linear regressions, with individual correlations of about 0.98. Data obtained
      with the CR10 scale could also be described by linear regressions, but when
      described by power functions gave exponents of about 1.2 (SD approximately 0.4)
      (with one additional constant included in the power function). This was
      significantly lower than the exponent of between 1.5 and 1.9 that has previously
      been observed. Mean individual correlations were 0.98. Blood lactate
      concentration grew with monotonously increasing functions that could be described
      by power functions with a mean exponent of about 2.6 (SD approximately 0.6) (with
      two additional constants included in the power functions). In the second study,
      where also the more recently developed Borg CR100 scale (centiMax) was included,
      24 healthy subjects (12 men and 12 women) with a mean age of about 29 years (SD
      approximately 3) participated in a work test with a step-wise increase of work
      loads (25 W) every third minute. Ratings and HRs were recorded. RPE values were
      described by linear regressions with individual correlations of about 0.97. Data
      from the two CR scales were described by power functions with mean exponents of
      about 1.4 (SD approximately 0.5) (with a-values in the power functions). Mean
      individual correlations were about 0.98. In both studies, a tendency for a
      deviation from linearity between RPE values and HRs was observed. The obtained
      deviations from what has previously been obtained for work of longer duration (4
      6 min) points to a need for standardization of work-test protocols and to the
      advantage of using CR scales.

PMID- 16430683
TI  - Stroke volume and the endurance athlete.

PMID- 16430685
TI  - Iron-sulphur clusters and the problem with oxygen.
AB  - During the first billion years of life on the Earth, the environment was
      anaerobic. Iron and sulphur were plentiful, and they were recruited in the
      formation of iron-sulphur (Fe-S) clusters within ancient proteins. These clusters
      provided many enzymes with the ability to transfer electrons; to others they
      offered a cationic feature that tightly bound oxyanionic and nitrogenous
      metabolites. Still others acquired a crystallizing surface around which
      polypeptide could fold to establish a three-dimensional structure. However, the
      subsequent oxygenation of the Earth's atmosphere by photosynthetic organisms
      created a threat to cluster-dependent proteins that still has not been fully
      resolved. By oxidizing environmental iron, oxygen limits its bioavailability,
      requiring that organisms employ complex schemes with which to satisfy their iron
      requirement. More directly, oxygen species convert exposed Fe-S clusters to
      unstable forms that quickly decompose. Some microbes responded to this dilemma by
      retreating to anaerobic habitats. Others abandoned the use of low-potential
      electron-transfer pathways, which rely upon the least stable cluster enzymes, and
      developed antioxidant strategies to protect the remainder. These adjustments were
      only partially successful: largely because of their reliance upon Fe-S clusters,
      aerobes remain vulnerable to iron restriction and oxidative stress, features that
      higher organisms exploit in defending themselves against bacterial pathogens.
      Thus, the history of Fe-S clusters is an unusual one that has profoundly shaped
      contemporary microbial ecology.

PMID- 16430686
TI  - The Pseudomonas aeruginosa type IV pilin receptor binding domain functions as an
      adhesin for both biotic and abiotic surfaces.
AB  - Pseudomonas aeruginosa readily binds to stainless steel and other abiotic
      surfaces, causing major problems in both the medical and food industries. In this
      study, we show that P. aeruginosa binds to abiotic surfaces in a concentration
      dependent, saturable manner during the initial stages of biofilm formation. P.
      aeruginosa type IV pili mediate binding to stainless steel as a pilus-deficient
      strain does not bind to steel, purified type IV pili bound in a concentration
      dependent, saturable manner, and purified pili competitively inhibited whole cell
      binding. PAK pili can also bind polystyrene and polyvinylchloride in a
      concentration-dependant and saturable manner. As an antibody specific for the C
      terminal pilin receptor binding domain inhibited adherence to abiotic surfaces,
      the role of the C-terminal receptor binding domain in mediating binding to steel
      surfaces was examined. A synthetic peptide of the PAK pilin epithelial cell
      receptor binding domain [PAK(128-144)ox] bound directly to steel with high
      affinity. The interaction of pili with steel was specifically inhibited by this
      peptide with an apparent Ki of approximately 0.2 nM and effectively inhibited the
      binding of viable homologous and heterologous P. aeruginosa strains to steel with
      an apparent Ki of approximately 4 nM. A single point mutation (K130I) in the PAO
      receptor binding domain was observed to abolish binding to stainless steel while
      binding to human buccal epithelial cells was enhanced. Therefore, the C-terminal
      receptor binding domain appears to have evolved for binding a variety of
      surfaces.

PMID- 16430688
TI  - A characterization of DNA release in Pseudomonas aeruginosa cultures and
      biofilms.
AB  - Pseudomonas aeruginosa produces extracellular DNA which functions as a cell-to
      cell interconnecting matrix component in biofilms. Comparison of extracellular
      DNA and chromosomal DNA by the use of polymerase chain reaction and Southern
      analysis suggested that the extracellular DNA is similar to whole-genome DNA.
      Evidence that the extracellular DNA in P. aeruginosa biofilms and cultures is
      generated via lysis of a subpopulation of the bacteria was obtained through
      experiments where extracellular beta-galactosidase released from lacZ-containing
      P. aeruginosa strains was assessed. Experiments with the wild type and lasIrhlI,
      pqsA, pqsL and fliMpilA mutants indicated that the extracellular DNA is generated
      via a mechanism which is dependent on acyl homoserine lactone and Pseudomonas
      quinolone signalling, as well as on flagella and type IV pili. Microscopic
      investigation of flow chamber-grown wild-type P. aeruginosa biofilms stained with
      different DNA stains suggested that the extracellular DNA is located primarily in
      the stalks of mushroom-shaped multicellular structures, with a high concentration
      especially in the outer part of the stalks forming a border between the stalk
      forming bacteria and the cap-forming bacteria. Biofilms formed by lasIrhlI, pqsA
      and fliMpilA mutants contained less extracellular DNA than biofilms formed by the
      wild type, and the mutant biofilms were more susceptible to treatment with sodium
      dodecyl sulphate than the wild-type biofilm.

PMID- 16430687
TI  - Evidence that the SpoIIIE DNA translocase participates in membrane fusion during
      cytokinesis and engulfment.
AB  - During Bacillus subtilis sporulation, SpoIIIE is required for translocation of
      the trapped forespore chromosome across the sporulation septum, for
      compartmentalization of cell-specific gene expression, and for membrane fusion
      after engulfment. We isolated mutations within the SpoIIIE membrane domain that
      block localization and function. One mutant protein initially localizes normally
      and completes DNA translocation, but shows reduced membrane fusion after
      engulfment. Fluorescence recovery after photobleaching experiments demonstrate
      that in this mutant the sporulation septum remains open, allowing cytoplasmic
      contents to diffuse between daughter cells, suggesting that it blocks membrane
      fusion after cytokinesis as well as after engulfment. We propose that SpoIIIE
      catalyses these topologically opposite fusion events by assembling or
      disassembling a proteinaceous fusion pore. Mutants defective in SpoIIIE assembly
      also demonstrate that the ability of SpoIIIE to provide a diffusion barrier is
      directly proportional to its ability to assemble a focus at the septal midpoint
      during DNA translocation. Thus, SpoIIIE mediates compartmentalization by two
      distinct mechanisms: the SpoIIIE focus first provides a temporary diffusion
      barrier during DNA translocation, and then mediates the completion of membrane
      fusion after division to provide a permanent diffusion barrier. SpoIIIE-like
      proteins might therefore serve to couple the final step in cytokinesis, septal
      membrane fusion, to the completion of chromosome segregation.

PMID- 16430689
TI  - DNA repair, a novel antibacterial target: Holliday junction-trapping peptides
      induce DNA damage and chromosome segregation defects.
AB  - Holliday junction intermediates arise in several central pathways of DNA repair,
      replication fork restart, and site-specific recombination catalysed by tyrosine
      recombinases. Previously identified hexapeptide inhibitors of phage lambda
      integrase-mediated recombination block the resolution of Holliday junction
      intermediates in vitro and thereby inhibit recombination, but have no DNA
      cleavage activity themselves. The most potent peptides are specific for the
      branched DNA structure itself, as opposed to the integrase complex. Based on this
      activity, the peptides inhibit several unrelated Holliday junction-processing
      enzymes in vitro, including the RecG helicase and RuvABC junction resolvase
      complex. We have found that some of these hexapeptides are potent bactericidal
      antimicrobials, effective against both Gm+ and Gm- bacteria. Using
      epifluorescence microscopy and flow cytometry, we have characterized extensively
      the physiology of bacterial cells treated with these peptides. The hexapeptides
      cause DNA segregation abnormalities, filamentation and DNA damage. Damage caused
      by the peptides induces the SOS response, and is synergistic with damage caused
      by UV and mitomycin C. Our results are consistent with the model that the
      hexapeptides affect DNA targets that arise during recombination-dependent repair.
      We propose that the peptides trap intermediates in the repair of collapsed
      replication forks, preventing repair and resulting in bacterial death. Inhibition
      of DNA repair constitutes a novel target of antibiotic therapy. The peptides
      affect targets that arise in multiple pathways, and as expected, are quite
      resistant to the development of spontaneous antibiotic resistance.

PMID- 16430690
TI  - Mutator mutants of Escherichia coli carrying a defect in the DNA polymerase III
      tau subunit.
AB  - To investigate the possible role of accessory subunits of Escherichia coli DNA
      polymerase III holoenzyme (HE) in determining chromosomal replication fidelity,
      we have investigated the role of the dnaX gene. This gene encodes both the tau
      and gamma subunits of HE, which play a central role in the organization and
      functioning of HE at the replication fork. We find that a classical, temperature
      sensitive dnaX allele, dnaX36, displays a pronounced mutator effect,
      characterized by an unusual specificity: preferential enhancement of
      transversions and -1 frameshifts. The latter occur predominantly at non-run
      sequences. The dnaX36 defect does not affect the gamma subunit, but produces a
      tau subunit carrying a missense substitution (E601K) in its C-terminal domain
      (domain V) that is involved in interaction with the Pol III alpha subunit. A
      search for new mutators in the dnaX region of the chromosome yielded six
      additional dnaX mutators, all carrying a specific tau subunit defect. The new
      mutators displayed phenotypes similar to dnaX36: strong enhancement of
      transversions and frameshifts and only weak enhancement for transitions. The
      combined findings suggest that the tau subunit of HE plays an important role in
      determining the fidelity of the chromosomal replication, specifically in the
      avoidance of transversions and frameshift mutations.

PMID- 16430691
TI  - Cell cycle-dependent expression regulation by the proteasome pathway and
      characterization of the nuclear targeting signal of a Leishmania major Kin-13
      kinesin.
AB  - The LmjF01.0030 gene of Leishmania major Friedlin, annotated as 'MCAK-like', was
      confirmed as a kinesin with an internally located motor domain and termed
      LmjKIN13-1. Both the native form of the protein and a green fluorescent protein
      (GFP)-fused recombinant version were shown to be exclusively intranuclear, and,
      more specifically, to localize to the spindle and spindle poles. Cell cycle
      dependent regulation of the protein levels was demonstrated using synchronized
      Leishmania cells: LmjKIN13-1 was highly abundant in the G2+M phase and present at
      very low levels after mitosis. Altogether, these features suggest that this
      protein participates in mitosis. The construction of systematic deletion mutants
      allowed the localization of the primary sequence regions responsible for nuclear
      targeting on the one hand, and for cell cycle-dependent variations on the other
      hand. A 42-amino-acid region of the carboxy(C)-terminal domain mediates nuclear
      import and could be defined as an atypical nuclear localization signal. Protein
      level regulation during the cell cycle was shown to also depend upon the C
      terminal domain, where apparently redundant degradation signals are present.
      Putative degradation signals appear to be present on both sides and inside the
      nuclear localization signal. Further experiments strongly suggest a role for the
      ubiquitin/proteasome pathway in this cell cycle-dependent regulation. These data
      underline the importance of post-translational regulation of protein abundance in
      this ancestral eukaryote where transcriptional regulation seems to be rare or
      near absent.

PMID- 16430692
TI  - A calcium-dependent protein kinase regulates Plasmodium ookinete access to the
      midgut epithelial cell.
AB  - Plasmodium parasites are fertilized in the mosquito midgut and develop into
      motile zygotes, called ookinetes, which invade the midgut epithelium. Here we
      show that a calcium-dependent protein kinase, CDPK3, of the rodent malarial
      parasite (Plasmodium berghei) is produced in the ookinete stage and has a
      critical role in parasite transmission to the mosquito vector. Targeted
      disruption of the CDPK3 gene decreased ookinete ability to infect the mosquito
      midgut by nearly two orders of magnitude. Electron microscopic analyses
      demonstrated that the disruptant ookinetes could not access midgut epithelial
      cells by traversing the layer covering the cell surface. An in vitro migration
      assay showed that these ookinetes lack the ability to migrate through an
      artificial gel, suggesting that this defect caused their failure to access the
      epithelium. In vitro migration assays also suggested that this motility is
      induced in the wild type by mobilization of intracellular stored calcium. These
      results indicate that a signalling pathway involving calcium and CDPK3 regulates
      ookinete penetration of the layer covering the midgut epithelium. Because humans
      do not possess CDPK family proteins, CDPK3 is a good target for blocking malarial
      transmission to the mosquito vector.

PMID- 16430693
TI  - Iron acquisition systems for ferric hydroxamates, haemin and haemoglobin in
      Listeria monocytogenes.
AB  - Listeria monocytogenes is a Gram-positive bacterium that causes severe
      opportunistic infections in humans and animals. We biochemically characterized,
      for the first time, the iron uptake processes of this facultative intracellular
      pathogen, and identified the genetic loci encoding two of its membrane iron
      transporters. Strain EGD-e used iron complexes of hydroxamates (ferrichrome and
      ferrichrome A, ferrioxamine B), catecholates (ferric enterobactin, ferric
      corynebactin) and eukaryotic binding proteins (transferrin, lactoferrin,
      ferritin, haemoglobin). Quantitative determinations showed 10-100-fold lower
      affinity for ferric siderophores (Km approximately 1-10 nM) than Gram-negative
      bacteria, and generally lower uptake rates. Vmax for [59Fe]-enterobactin (0.15
      pMol per 10(9) cells per minute) was 400-fold lower than that of Escherichia
      coli. For [59Fe]-corynebactin, Vmax was also low (1.2 pMol per 10(9) cells per
      minute), but EGD-e transported [59Fe]-apoferrichrome similarly to E. coli
      (Vmax=24 pMol per 10(9) cells per minute). L. monocytogenes encodes potential Fur
      regulated iron transporters at 2.031 Mb (the fur-fhu region), 2.184 Mb (the feo
      region), 2.27 Mb (the srtB region) and 2.499 Mb (designated hupDGC region).
      Chromosomal deletions in the fur-fhu and hupDGC regions diminished iron uptake
      from ferric hydroxamates and haemin/haemoglobin respectively. In the former
      locus, deletion of fhuD (lmo1959) or fhuC (lmo1960) strongly reduced [59Fe]
      apoferrichrome uptake. Deletion of hupC (lmo2429) eliminated the uptake of haemin
      and haemoglobin, and decreased the virulence of L. monocytogenes 50-fold in mice.
      Elimination of srtB region genes (Deltalmo2185, Deltalmo2186, Deltalmo2183), both
      sortase structural genes (DeltasrtB, DeltasrtA, DeltasrtAB), fur and feoB did not
      impair iron transport. However, deletion of bacterioferritin (Deltafri, lmo943;
      0.97 Mb) decreased growth and altered iron uptake: Vmax of [59Fe]-corynebactin
      transport tripled in this strain, whereas that of [59Fe]-apoferrichrome decreased
      20-fold.

PMID- 16430694
TI  - Interactions between the YycFG and PhoPR two-component systems in Bacillus
      subtilis: the PhoR kinase phosphorylates the non-cognate YycF response regulator
      upon phosphate limitation.
AB  - Two-component signal transduction systems (TCS) are an important mechanism by
      which bacteria sense and respond to their environment. Although each two
      component system appears to detect and respond to a specific signal(s), it is now
      evident that they do not always act independently of each other. In this paper we
      present data indicating regulatory links between the PhoPR two-component system
      that participates in the cellular response to phosphate limitation, and the
      essential YycFG two-component system in Bacillus subtilis. We show that the PhoR
      sensor kinase can activate the YycF response regulator during a phosphate
      limitation-induced stationary phase, and that this reaction occurs in the
      presence of the cognate YycG sensor kinase. Phosphorylation of YycF by PhoR also
      occurs in vitro, albeit at a reduced level. However, the reciprocal cross
      phosphorylation does not occur. A second level of interaction between PhoPR and
      YycFG is indicated by the fact that cells depleted for YycFG have a severely
      deficient PhoPR-dependent phosphate limitation response and that YycF can bind
      directly to the promoter of the phoPR operon. YycFG-depleted cells neither
      activate expression of phoA and phoPR nor repress expression of the essential
      tagAB and tagDEF operons upon phosphate limitation. This effect is specific to
      the PhoPR-dependent phosphate limitation response because PhoPR-independent
      phosphate limitation responses can be initiated in YycFG-depleted cells.

PMID- 16430695
TI  - Targets of the master regulator of biofilm formation in Bacillus subtilis.
AB  - Wild strains of the spore-forming bacterium Bacillus subtilis are capable of
      forming architecturally complex communities of cells. The formation of these
      biofilms is mediated in part by the 15-gene exopolysaccharide operon, epsA-O,
      which is under the direct negative control of the SinR repressor. We report the
      identification of an additional operon, yqxM-sipW-tasA, that is required for
      biofilm formation and is under the direct negative control of SinR. We now show
      that all three members of the operon are required for the formation of robust
      biofilms and that SinR is a potent repressor of the operon that acts by binding
      to multiple sites in the promoter region. Genome-wide analysis of SinR-controlled
      transcription indicates that the epsA-O and yqxM-sipW-tasA operons constitute
      many of the most strongly controlled genes in the SinR regulon. These findings
      reinforce the view that SinR is a master regulator for biofilm formation and
      further suggest that a principal biological function of SinR is to govern the
      assembly of complex multicellular communities.

PMID- 16430696
TI  - A major protein component of the Bacillus subtilis biofilm matrix.
AB  - Microbes construct structurally complex multicellular communities (biofilms)
      through production of an extracellular matrix. Here we present evidence from
      scanning electron microscopy showing that a wild strain of the Gram positive
      bacterium Bacillus subtilis builds such a matrix. Genetic, biochemical and
      cytological evidence indicates that the matrix is composed predominantly of a
      protein component, TasA, and an exopolysaccharide component. The absence of TasA
      or the exopolysaccharide resulted in a residual matrix, while the absence of both
      components led to complete failure to form complex multicellular communities.
      Extracellular complementation experiments revealed that a functional matrix can
      be assembled even when TasA and the exopolysaccharide are produced by different
      cells, reinforcing the view that the components contribute to matrix formation in
      an extracellular manner. Having defined the major components of the biofilm
      matrix and the control of their synthesis by the global regulator SinR, we
      present a working model for how B. subtilis switches between nomadic and
      sedentary lifestyles.

PMID- 16430697
TI  - Specificity of the trypanothione-dependent Leishmania major glyoxalase I:
      structure and biochemical comparison with the human enzyme.
AB  - Trypanothione replaces glutathione in defence against cellular damage caused by
      oxidants, xenobiotics and methylglyoxal in the trypanosomatid parasites, which
      cause trypanosomiasis and leishmaniasis. In Leishmania major, the first step in
      methylglyoxal detoxification is performed by a trypanothione-dependent glyoxalase
      I (GLO1) containing a nickel cofactor; all other characterized eukaryotic
      glyoxalases use zinc. In kinetic studies L. major and human enzymes were active
      with methylglyoxal derivatives of several thiols, but showed opposite substrate
      selectivities: N1-glutathionylspermidine hemithioacetal is 40-fold better with L.
      major GLO1, whereas glutathione hemithioacetal is 300-fold better with human
      GLO1. Similarly, S-4-bromobenzylglutathionylspermidine is a 24-fold more potent
      linear competitive inhibitor of L. major than human GLO1 (Kis of 0.54 microM and
      12.6 microM, respectively), whereas S-4-bromobenzylglutathione is >4000-fold more
      active against human than L. major GLO1 (Kis of 0.13 microM and >500 microM
      respectively). The crystal structure of L. major GLO1 reveals differences in
      active site architecture to both human GLO1 and the nickel-dependent Escherichia
      coli GLO1, including increased negative charge and hydrophobic character and
      truncation of a loop that may regulate catalysis in the human enzyme. These
      differences correlate with the differential binding of glutathione and
      trypanothione-based substrates, and thus offer a route to the rational design of
      L. major-specific GLO1 inhibitors.

PMID- 16430698
TI  - Identification and functional characterization of EhClC-A, an Entamoeba
      histolytica ClC chloride channel located at plasma membrane.
AB  - ClC chloride channels perform a wide variety of physiological functions and they
      had been characterized in animals, yeast, plants and bacteria but not in
      protozoa. By blast search we found in Entamoeba histolytica, the protozoan
      responsible for human amoebiasis, two genes (Ehclc-A and Ehclc-B) encoding for
      putative polypeptides with 25-30% identity to ClC chloride channels of several
      organisms. Reverse transcription polymerase chain reaction (RT-PCR) experiments
      showed that both genes are transcribed in trophozoites. Phylogenetic analysis
      revealed that EhClC-A and EhClC-B polypeptides belong to the eukaryotic branch of
      plasma membrane ClCs. Specific antibodies against EhClC-A confirmed that it is
      located at the trophozoite plasma membrane. Xenopus laevis oocytes microinjected
      with Ehclc-A cRNA elicited anion currents not detected in oocytes microinjected
      with water. Induced currents were inwardly rectifying and had a permeability
      sequence of Cl->Br->I->F->>NO3-. The chloride channel blocker 4-acetamido
      4'isothiocyanostilbene-2, 2'-disulphonic acid (SITS) strongly inhibited the
      oocytes anion currents and trophozoites growth. Experiments at diverse pHs
      suggested that EhClC-A is not a Cl-/H+ exchanger, but it is an ion channel that
      could be involved in pH regulation. EhClC-A may also participate in cell volume
      regulation. As far as we know, EhClC-A is the first chloride channel
      characterized in protozoa.

PMID- 16430699
TI  - Mechanism of polarization of Listeria monocytogenes surface protein ActA.
AB  - The polar distribution of the ActA protein on the surface of the Gram-positive
      intracellular bacterial pathogen, Listeria monocytogenes, is required for
      bacterial actin-based motility and successful infection. ActA spans both the
      bacterial membrane and the peptidoglycan cell wall. We have directly examined the
      de novo ActA polarization process in vitro by using an ActA-RFP (red fluorescent
      protein) fusion. After induction of expression, ActA initially appeared at
      distinct sites along the sides of bacteria and was then redistributed over the
      entire cylindrical cell body through helical cell wall growth. The accumulation
      of ActA at the bacterial poles displayed slower kinetics, occurring over several
      bacterial generations. ActA accumulated more efficiently at younger, less inert
      poles, and proper polarization required an optimal balance between protein
      secretion and bacterial growth rates. Within infected host cells, younger
      generations of L. monocytogenes initiated motility more quickly than older ones,
      consistent with our in vitro observations of de novo ActA polarization. We
      propose a model in which the polarization of ActA, and possibly other Gram
      positive cell wall-associated proteins, may be a direct consequence of the
      differential cell wall growth rates along the bacterium and dependent on the
      relative rates of protein secretion, protein degradation and bacterial growth.

PMID- 16430700
TI  - The chromosomal relBE2 toxin-antitoxin locus of Streptococcus pneumoniae:
      characterization and use of a bioluminescence resonance energy transfer assay to
      detect toxin-antitoxin interaction.
AB  - Proteic toxin-antitoxin (TA) loci were first identified in bacterial plasmids,
      and they were regarded as involved in stable plasmid maintenance by a so-called
      'addiction' mechanism. Later, chromosomally encoded TA loci were identified and
      their function ascribed to survival mechanisms when bacteria were subjected to
      stress. In the search for chromosomally encoded TA loci in Gram-positive
      bacteria, we identified various in the pathogen Streptococcus pneumoniae. Two of
      these cassettes, sharing homology with the Escherichia coli relBE locus were
      cloned and tested for their activity. The relBE2Spn locus resulted to be a bona
      fide TA locus. The toxin exhibited high toxicity towards E. coli and S.
      pneumoniae, although in the latter, the chromosomal copy of the antitoxin
      relB2Spn gene had to be inactivated to detect full toxicity. Cell growth arrest
      caused by expression of the relE2Spn toxin gene could be reverted by expression
      of the cognate antitoxin, relB2Spn, although prolonged exposition to the toxin
      led to cell death. The pneumococcal relBE2Spn locus is the first instance of a
      chromosomally encoded TA system from Gram-positive bacteria characterized in its
      own host. We have developed a bioluminescence resonance energy transfer (BRET)
      assay to detect the interactions between the RelB2Spn antitoxin and the RelE2Spn
      toxin in vivo. This technique has shown to be amenable to a high-throughput
      screening (HTS), opening new avenues in the search of molecules with potential
      antibacterial activity able to inhibit TA interactions.

PMID- 16430701
TI  - New insights into the pneumococcal fratricide: relationship to clumping and
      identification of a novel immunity factor.
AB  - In 1971, Tomasz and Zanati discovered that competent pneumococci have a tendency
      to form aggregates when pelleted by centrifugation and resuspended in 0.01 N HCl
      by brief vortexing. Interestingly, no clumping was observed with parallel
      cultures of non-competent cells treated in the same way. We set out to elucidate
      the mechanism behind this striking phenomenon, and were able to show that it
      depends on extracellular DNA that is presumably released by so-called competence
      induced cell lysis. Competence-induced cell lysis, which was first described a
      few years ago, seems to rely on the concerted action of several murein
      hydrolases. Our results confirmed and extended previous findings by showing that
      competence-induced aggregation is abolished in a lytA-lytC double mutant, and
      absolutely requires CbpD and its N-terminal CHAP amidase domain. Furthermore, we
      discovered a novel competence stimulating peptide (CSP)-induced immunity protein,
      encoded by the early competence gene comM (spr1762), which protects competent
      pneumococci against their own lysins. Together, the murein hydrolases and the
      immunity protein constitutes a CSP-controlled mechanism that allows competent
      pneumococci to commit fratricide by killing non-competent pneumococci sharing the
      same ecological niche. Through such predatory behaviour, pneumococci can get
      access to transforming DNA and nutrients, promote the release of virulence
      factors, and at the same time get rid of competitors.

PMID- 16430702
TI  - An exonuclease I-sensitive DNA repair pathway in Deinococcus radiodurans: a major
      determinant of radiation resistance.
AB  - Deinococcus radiodurans R1 recovering from acute dose of gamma radiation shows a
      biphasic mechanism of DNA double-strand break repair. The possible involvement of
      microsequence homology-dependent, or non-homologous end joining type mechanisms
      during initial period followed by RecA-dependent homologous recombination
      pathways has been suggested for the reconstruction of complete genomes in this
      microbe. We have exploited the known roles of exonuclease I in DNA recombination
      to elucidate the nature of recombination involved in DNA double-strand break
      repair during post-irradiation recovery of D. radiodurans. Transgenic Deinococcus
      cells expressing exonuclease I functions of Escherichia coli showed significant
      reduction in gamma radiation radioresistance, while the resistance to far-UV and
      hydrogen peroxide remained unaffected. The overexpression of E. coli exonuclease
      I in Deinococcus inhibited DNA double-strand break repair. Such cells exhibited
      normal post-irradiation expression kinetics of RecA, PprA and single-stranded DNA
      binding proteins but lacked the divalent cation manganese [(Mn(II)]-dependent
      protection from gamma radiation. The results strongly suggest that 3' (rho) 5'
      single-stranded DNA ends constitute an important component in recombination
      pathway involved in DNA double-strand break repair and that absence of sbcB from
      deinococcal genome may significantly aid its extreme radioresistance phenotype.

PMID- 16430703
TI  - Minimal requirements for oxygen sensing by the aerotaxis receptor Aer.
AB  - The PAS and HAMP domain superfamilies are signal transduction modules found in
      all kingdoms of life. The Aer receptor, which contains both domains, initiates
      rapid behavioural responses to oxygen (aerotaxis) and other electron acceptors,
      guiding Escherichia coli to niches where it can generate optimal cellular energy.
      We used intragenic complementation to investigate the signal transduction pathway
      from the Aer PAS domain to the signalling domain. These studies showed that the
      HAMP domain of one monomer in the Aer dimer stabilized FAD binding to the PAS
      domain of the cognate monomer. In contrast, the signal transduction pathway was
      intra-subunit, involving the PAS and signalling domains from the same monomer.
      The minimal requirements for signalling were investigated in heterodimers
      containing a full-length and truncated monomer. Either the PAS or signalling
      domains could be deleted from the non-signalling subunit of the heterodimer, but
      removing 16 residues from the C-terminus of the signalling subunit abolished
      aerotaxis. Although both HAMP domains were required for aerotaxis, signalling was
      not disrupted by missense mutations in the HAMP domain from the signalling
      subunit. Possible models for Aer signal transduction are compared.

PMID- 16430704
TI  - The DnaK chaperone machinery converts the native FlhD2C2 hetero-tetramer into a
      functional transcriptional regulator of flagellar regulon expression in
      Salmonella.
AB  - The DnaK chaperone binds non-specifically to many unfolded polypeptides and also
      binds selectively to specific substrates. Although its involvement in targeting
      the unfolded polypeptides to assist proper folding is well documented, less is
      known about its role in targeting the folded polypeptides. We demonstrate that
      DnaK regulates the expression of the Salmonella flagellar regulon by modulating
      the FlhD and FlhC proteins, which function as master regulators at the apex of a
      transcription hierarchy comprising three classes of genes. FlhD and FlhC form an
      FlhD2C2 complex that activates sigma70 promoter of class 2 genes. In DeltadnaK
      cells, FlhD and FlhC proteins seemed to be assembled into hetero-tetrameric
      FlhD2C2 but the complex was not fully active in class 2 gene transcription,
      suggesting that the DnaK chaperone is involved in activating native FlhD2C2
      complex into a regulator of flagellar regulon expression. This is the first time
      that involvement of the DnaK chaperone machinery in activating folded
      oligomerized proteins has been demonstrated.

PMID- 16430705
TI  - Predicting metals sensed by ArsR-SmtB repressors: allosteric interference by a
      non-effector metal.
AB  - Many bacterial genomes encode multiple metal-sensing ArsR-SmtB transcriptional
      repressors. There is interest in understanding and predicting their metal
      specificities. Here we analyse two arsR-smtB genes, ydeT and yozA (now aseR and
      czrA) from Bacillus subtilis. Purified AseR and CzrA formed complexes in gel
      retardation and fluorescence-anisotropy assays with fragments of promoters that
      were derepressed in DeltaaseR and DeltaczrA cells. Candidate (i) partly thiolate,
      alpha3-helix (for AseR) and (ii) tetrahedral, non-thiolate, alpha5-helix (for
      CzrA) metal binding sites were predicted then tested in vitro and/or in vivo. The
      precedents are for such sites to sense arsenite/antimonite (alpha3) and zinc
      (alpha5). This correlated with the respective metal inducers of AseR and CzrA
      repressed promoters in B. subtilis and matched the metals that impaired formation
      of protein-DNA complexes in vitro. The putative sensory sites of 1024 ArsR-SmtB
      homologues are reported. Although AseR did not sense zinc in vivo, it bound zinc
      in vitro exploiting alpha3 thiols, but AseR DNA binding was not impaired by zinc.
      If selectivity relies on discriminatory triggering of allostery not just
      selective metal binding, then tight non-effector metal complexes could
      theoretically inhibit metal sensing. AseR remained arsenite-sensitive in
      equimolar zinc, while CzrA remained zinc-sensitive in equimolar arsenite in
      vitro. However, cupric ions did not impair CzrA-DNA complex formation but did
      inhibit zinc-mediated allostery in vitro and prevent zinc binding. Access to
      copper must be controlled in vivo to avoid formation of cupric CzrA.

PMID- 16430706
TI  - Does growth hormone cause cancer?
AB  - The ability of GH, via its mediator peptide IGF-1, to influence regulation of
      cellular growth has been the focus of much interest in recent years. In this
      review, we will explore the association between GH and cancer. Available
      experimental data support the suggestion that GH/IGF-1 status may influence
      neoplastic tissue growth. Extensive epidemiological data exist that also support
      a link between GH/IGF-1 status and cancer risk. Epidemiological studies of
      patients with acromegaly indicate an increased risk of colorectal cancer,
      although risk of other cancers is unproven, and a long-term follow-up study of
      children deficient in GH treated with pituitary-derived GH has indicated an
      increased risk of colorectal cancer. Conversely, extensive studies of the outcome
      of GH replacement in childhood cancer survivors show no evidence of an excess of
      de novo cancers, and more recent surveillance of children and adults treated with
      GH has revealed no increase in observed cancer risk. However, given the
      experimental evidence that indicates GH/IGF-1 provides an anti-apoptotic
      environment that may favour survival of genetically damaged cells, longer-term
      surveillance is necessary; over many years, even a subtle alteration in the
      environmental milieu in this direction, although not inducing cancer, could
      result in acceleration of carcinogenesis. Finally, even if GH/IGF-1 therapy does
      result in a small increase in cancer risk compared to untreated patients with GH
      deficiency, it is likely that the eventual risk will be the same as the general
      population. Such a restoration to normality will need to be balanced against the
      known morbidity of untreated GH deficiency.

PMID- 16430707
TI  - Growth hormone and cancer: are we asking the right questions?*.

PMID- 16430708
TI  - Lack of association between serum TSH or free T4 and body mass index in euthyroid
      subjects.
AB  - BACKGROUND: There is ongoing debate regarding the influence of minor changes in
      thyroid status within the normal range and body mass index (BMI). Overt thyroid
      dysfunction is well recognized to affect weight, but the influence of minor
      perturbations of thyroid function remains unclear. AIM OF THE STUDY: To examine
      in euthyroid subjects the association of serum concentrations of TSH and free T4
      within the normal range and BMI. To compare serum TSH and free T4 concentrations
      in nonobese and obese subjects. SUBJECTS AND METHODS: A cohort of 401 euthyroid
      subjects with normal serum TSH (361 females, 40 males, mean age 48.2 years) who
      had been referred to a Thyroid Clinic due to the presence of a thyroid nodule or
      goitre. Measurements of serum TSH and free T4 were recorded, together with BMI
      (calculated from weight and height). Associations between measures of TSH, free
      T4 and BMI were investigated. RESULTS: There was no association between either
      serum TSH or free T4 concentration when considered as a continuous variable and
      BMI, and no difference in BMI when subjects were categorized according to serum
      TSH or free T4. There was also no difference in serum TSH or free T4 between lean
      and obese euthyroid subjects. Evidence of thyroid autoimmunity indicated by the
      presence of antibodies to thyroid peroxidase was likewise not associated with a
      difference in BMI. CONCLUSION: This study provides no evidence for an association
      between thyroid status within the normal range and BMI.

PMID- 16430709
TI  - The tumour necrosis factor (TNF)-alpha-308GA promoter polymorphism is related to
      prenatal growth and postnatal insulin resistance.
AB  - OBJECTIVE: Variation in the tumour necrosis factor gene, (TNF) has been
      associated with insulin resistance traits. We questioned whether the TNF-308G/A
      polymorphism is associated with birthweight and insulin resistance in children
      born small for gestational age (SGA), a patient population known to be at risk
      for insulin resistance. DESIGN: A cross-sectional, hospital-based study assessing
      insulin sensitivity in SGA children. PATIENTS: One hundred and ninety-eight
      school-age children born either SGA (n=90, age 7.4+/- 4.5 years) or appropriate
      for gestational age (AGA, n=108, age 8.7+/- 4.0 years). MEASUREMENTS: All
      children were genotyped for the TNF-308G/A polymorphism; a biochemical profile
      was also performed in prepubertal SGA (n=58) and AGA (n=57) subjects. RESULTS:
      Genotype frequencies for the TNF-308G/A single nucleotide polymorphisms (SNPs)
      (GG and GA/AA) differed between SGA and AGA children (86%vs. 72% and 14%vs. 28%,
      respectively; P=0.025). The GG genotype was associated with lower birthweight and
      birth length (2747.0+/- 23.3 g vs. 2851.0+/- 45.7 g, P=0.045, and 47.0+/- 0.2 cm
      vs. 48.2+/- 0.4 cm, P=0.011, respectively) and, in AGA but not in SGA children,
      with higher systolic blood pressure [103.3 (95% confidence interval (CI) 96.4
      110.2) mmHg vs. 92.8 (84.9-100.7) mmHg; P=0.028], higher blood glucose [4.8 (4.7
      5.0) mmol/l vs. 4.5 (4.3-4.8) mmol/l; P=0.042] and higher homeostasis model
      assessment for insulin resistance (HOMA-IR) index [1.4 (1.1-1.7) vs. 0.9 (0.4
      1.3); P=0.005]. In multivariate analysis, the TNF-308GG genotype was an
      independent predictor of HOMA-IR during childhood, explaining 8% of its variance.
      CONCLUSION: SGA children show increased frequency of the TNF-308G allele, an
      allele that is associated with prenatal growth and with postnatal insulin
      resistance. The TNF-308G/A polymorphism may have implications in the growth and
      metabolic abnormalities that characterise SGA children.

PMID- 16430710
TI  - Risk for severe hypoglycaemia with unawareness in GH-deficient patients during
      the insulin tolerance test.
AB  - OBJECTIVE: The insulin tolerance test (ITT) has been suggested as the gold
      standard for diagnosing GH deficiency (GHD). The ITT is, however, potentially
      hazardous. Glucose monitoring during the ITT varies between centres and there is
      surprisingly little information on the actual level of blood glucose nadir and
      the duration of hypoglycaemia in patients undergoing the ITT. The aim of the
      present study was to closely monitor the blood glucose level and to register the
      presence of symptoms and signs of hypoglycaemia during the ITT. DESIGN AND
      PATIENTS: Sixteen patients (seven women), aged 22-59 years were consecutively
      recruited for an ITT, and showed GHD (peak GH < 3 microg/l). RESULTS: In five
      (31%) of the patients unawareness of hypoglycaemia was recorded, the median nadir
      blood glucose level was 1.4 mmol/l (range 1.1-1.9) and the duration of blood
      glucose < 2.2 mmol/l was 25 min (range 20-33). The remaining 11 patients were
      symptomatic, and tiredness (n=6) and dizziness (n=3) were the most frequent
      symptoms. In these symptomatic patients the median nadir blood glucose level was
      1.3 mmol/l (range 1.0-1.6) and the duration of blood glucose < 2.2 mmol/l was 25
      min (range 15-30). CONCLUSIONS: In patients with GHD subjected to the ITT,
      symptoms of hypoglycaemia were scarce and a third showed unawareness. Close blood
      glucose monitoring is recommended at the ITT as low nadir blood glucose levels
      and long duration of hypoglycaemia may be present irrespective of symptoms of
      hypoglycaemia. Recommendations for intervention with intravenous glucose, at
      unacceptable low blood glucose levels or at prolonged hypoglycaemia, are
      warranted.

PMID- 16430711
TI  - Intravenous glucose intake independently related to intensive care unit and
      hospital mortality: an argument for glucose toxicity in critically ill patients.
AB  - OBJECTIVE: It is assumed that the toxic effects of glucose play a role in the
      outcome of critically ill patients. We studied the impact of the amount of
      infused glucose as a determinant of mortality. DESIGN: A retrospective cohort
      study design was used as blood glucose levels in critically ill patients are
      nowadays tightly controlled. PATIENTS: Long-stay critically ill patients (7-30
      days). MEASUREMENTS: The association between the mean amount of glucose infusion
      and both intensive care unit (ICU) and hospital mortality was determined. We
      corrected for the mean glucose serum concentration, the mean dosage of insulin
      and for severity of illness, using the acute physiology and chronic health
      evaluation (APACHE II) score. RESULTS: Of the 2,042 admitted patients, 273 met
      the inclusion criteria. The mean length of stay was 14.4 days [interquartile
      range (IQR) 9-18]. Hospital mortality was significantly lower for patients with a
      mean glucose level below 8 mmol/l (30/79; 38%) compared to patients with a level
      above 8 mmol/l (104/194; 54%, P=0.023). Logistic stepwise multivariate regression
      analysis for both ICU and hospital mortality as dependent variables showed that
      APACHE II score and the mean daily amount of infused glucose were associated with
      mortality. CONCLUSION: In long-stay ICU patients without blood glucose level
      control, the ICU and hospital mortality was independently related to the mean
      amount of infused glucose. In addition, mortality in patients with a mean glucose
      level above 8.0 mmol/l was higher. Both these determinants of mortality can exert
      their effects by insulin-independent uptake of glucose with subsequent toxic
      intracellular effects.

PMID- 16430712
TI  - Genetic analyses in familial isolated hyperparathyroidism: implication for
      clinical assessment and surgical management.
AB  - OBJECTIVE: Familial isolated primary hyperparathyroidism (FIPH) can result from
      either incomplete expression of a syndromic form of familial primary
      hyperparathyroidism [multiple endocrine neoplasia type 1 (MEN 1),
      hyperparathyroidism-jaw tumour syndrome (HPT-JT) or familial hypocalciuric
      hypercalcaemia (FHH)] or still unrecognized causes. Design Genetic analyses of
      MEN1, HRPT2 and CASR genes in FIHP. PATIENTS: Seven well-characterized Italian
      kindreds with FIHP, with negative clinical features for MEN 1, HPT-JT and FHH.
      The mean age (+/- SD) at diagnosis was 45 +/- 17 years (range 18-70 years) in the
      probands and 42 +/- 18 years (range 15-69 years) in the other affected subjects.
      MEASUREMENTS: Direct sequencing of germline DNA of the MEN1, HRPT2 and CASR genes
      from probands. The region of interest was amplified in some family members.
      RESULTS: Germline MEN1 mutations were detected in three kindreds. Multiglandular
      involvement was found in all but one affected subject belonging to the three
      kindreds with MEN1 mutations. In these patients persistence/relapse of the
      disease was observed unless an extensive parathyroidectomy (excision of 3(1)/(2)
      glands) had been performed, with the exception of one patient, who is currently
      normocalcaemic 168 months after excision of two glands. No mutations of MEN1,
      HRPT2 and CASR genes were identified in the remaining four families. CONCLUSIONS:
      MEN1 genotyping appears worthwhile in FIHP families, as the finding of
      mutation(s) may predict multiglandular involvement and therefore have practical
      surgical implications, and prompt further investigation in the family, with the
      possibility of identifying new cases and beginning a programme of periodic
      surveillance for emergence of tumours in all carriers.

PMID- 16430713
TI  - Hyperglycaemia after glucose loading is a major predictor of preclinical
      atherosclerosis in nondiabetic subjects.
AB  - OBJECTIVE: Carotid intima-media thickness (IMT) has proved to be an independent
      marker of preclinical atherosclerosis. The aim of this study was to determine
      whether carotid IMT is associated with the plasma glucose concentration in the
      fasting state, after loading with oral glucose, or with the insulin sensitivity
      index (ISI) in nondiabetic subjects with different levels of glucose intolerance
      and insulin resistance. DESIGN: Cross-sectional study. PATIENTS: A total of 160
      nondiabetic subjects (147 from our obesity-overweight clinic and 13 healthy
      normal subjects) were included in the present study, among them 33 had normal
      glucose tolerance (NGT), 13 had impaired fasting glucose (IFG), 80 had impaired
      glucose tolerance (IGT) and 34 had both IFG and IGT. MEASUREMENTS: Carotid IMT
      was assessed in the common carotid artery by a high-resolution B-mode ultrasound
      system. Plasma glucose was measured after fasting and at 30 min, 1, 2 and 3 h
      after a standard 75-g load of glucose. The ISI was calculated from the frequent
      sampling intravenous glucose tolerance test (FSIGT). Results The IMT values in
      the NGT group were lower than those in the IFG, IGT and IFG + IGT groups (P <
      0.03). No statistical difference in IMT values was found among the latter three
      groups. Univariate correlation analyses showed that the IMT was positively
      associated with age, plasma glucose concentrations 1 and 2 h after glucose
      loading, and serum concentration of low density lipoprotein (LDL) cholesterol
      (r=0.39, 0.22, 0.25 and 0.18, respectively, P<0.05). Multiple regression analysis
      showed that only age, plasma glucose concentration 2 h after glucose loading, and
      LDL cholesterol appeared to be significant correlates of the IMT (P<0.0001),
      whereas the ISI was not. CONCLUSIONS: In nondiabetic subjects with various
      degrees of glucose intolerance, there was a significant increase in IMT in those
      with IFG and IGT. Significant determinants of IMT, an indicator of preclinical
      atherosclerosis, include hyperglycaemia 2 h after a glucose load, age and LDL
      cholesterol, whereas fasting glucose concentration and the ISI were not
      significantly associated with IMT.

PMID- 16430714
TI  - Thyrotoxic periodic paralysis and polymorphisms of sodium-potassium ATPase genes.
AB  - OBJECTIVE: Thyrotoxic periodic paralysis (TPP) is a complication of
      hyperthyroidism association with recurrent, reversible episodes of muscle
      weakness. Increased sodium-potassium ATPase (Na/K-ATPase) pump activity is
      postulated to contribute to the hypokalaemic paralytic attacks in TPP. The aim of
      this study was to determine the genetic predisposition to TPP in relation to Na/K
      ATPase genes. DESIGN: A case-control association study. PATIENTS: Ninety-nine
      male Chinese TPP patients were compared to 84 male Graves' disease (GD) patients
      without TPP and 100 normal male controls. MEASUREMENT: A total of 1500 base pairs
      upstream of the transcriptional start site of the five Na/K-ATPase genes that are
      expressed in the skeletal muscles, namely ATP1A1, ATP1A2, ATP1B1, ATP1B2 and
      ATP1B4, were sequenced in all subjects for mutations or polymorphisms. The single
      nucleotide polymorphisms (SNPs) of the coding regions of the five genes were also
      studied for association with TPP. RESULTS: No mutations were detected in the 5'
      regions of the five genes in any of the patients studied. There was no difference
      in the distribution of SNPs and SNP haplotypes in the upstream and coding region
      of these genes between the three groups of subjects. CONCLUSION: No association
      between the polymorphisms of ATP1A1, ATP1A2, ATP1B1, ATP1B2 and ATP1B4 genes and
      TPP could be detected.

PMID- 16430715
TI  - Does birthweight predict adolescent adiponectin levels?
AB  - OBJECTIVE: Low birthweight is associated with insulin resistance later in life,
      and adiponectin is known to play an important role in insulin resistance. We have
      investigated whether birthweight has a relationship with adiponectin levels in
      adolescence. PATIENTS: An at-home questionnaire survey was completed by 660
      middle-school students (aged 12-15 years) in Seoul, Korea, and 152 participants
      were selected randomly based on their birthweight. MEASUREMENTS Subjects were
      separated into three groups according to birthweight. We recorded the birthweight
      and measured anthropometric factors including blood pressure, lipid profile,
      homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell
      function (HOMA-beta), and adiponectin levels of the subjects. These parameters
      were compared among the groups. The relationship between birthweight and
      physiological characteristics in adolescence was examined. RESULTS: Systolic
      blood pressure, lipid profiles and fasting plasma glucose were not significantly
      different among the groups, but diastolic blood pressure was lower in the third
      tertile. Insulin, C-peptide and HOMA-IR were higher in the low birthweight
      tertile. After adjustment for confounding factors, birthweight was inversely
      related to diastolic blood pressure, insulin, C-peptide and HOMA-IR. Adiponectin
      level had a significant relationship with current body mass index (BMI) (r=
      0.291; P< 0.001) but not with birthweight (r = 0.117; P = 0.166). CONCLUSIONSP:
      Although birthweight is closely related to insulin resistance during adolescence,
      adiponectin levels during adolescence had no significant relationship with
      birthweight. This result implies that low birthweight may not permanently affect
      adiponectin levels, but current body size is more closely associated with a
      decreased adiponectin level. However, the limited importance of birthweight as a
      determining factor on the adiponectin level later in life needs to be further
      evaluated.

PMID- 16430716
TI  - Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in
      skeletal muscle membrane phospholipids of obese subjects. Implications for
      insulin sensitivity.
AB  - OBJECTIVE: Cross-sectional studies suggest that the fatty acid (FA) composition
      of phospholipids in skeletal muscle cell membrane may modulate insulin
      sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary
      intervention on membrane FA composition and insulin sensitivity. DESIGN Muscle
      membrane FA profiles were determined in muscle (vastus lateralis) biopsies from
      21 obese subjects before and after 6 months of dietary restriction. Diet
      instructions emphasized low intake of FA of marine origin by recommending lean
      fish and prohibiting fatty fish and fish oil supplements. Insulin resistance was
      estimated by the homeostasis model assessment (HOMA-IR). RESULTS The mean weight
      loss was 5.1 kg (range -15.3 to +1.3 kg). BMI decreased from 36.5 to 34.9 kg/m(2)
      (P=0.003). Saturated FA (SFA) decreased 11% (P=0.0001). Polyunsaturated FA
      (PUFA)n-6 increased 4% (P =0.003). Long-chain PUFAn-3 increased 51% (P= 0.0001),
      mainly due to a 75% increase (P<0.0001) in docosahexaenoic acid. Changes in HOMA
      IR correlated significantly with changes in long-chain PUFAn-3 (R=-0.57, P<
      0.01), SFA (R=0.58, P<0.01) and waist circumference (R=0.46, P<0.05). A
      multivariate linear regression analysis that included changes in weight, fat
      mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3
      indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR
      (R(2)=0.33, P<0.01). CONCLUSIONS: A hypocaloric low-fat dietary intervention
      programme increased incorporation of long-chain PUFAn-3 and reduced SFA in
      skeletal muscle membrane phospholipids of obese subjects, a setting that may
      impact on insulin action.

PMID- 16430717
TI  - Association of HLA DQ4-DR8 haplotype with papillary thyroid carcinomas.
AB  - OBJECTIVE: The association of the human leucocyte antigen (HLA) system with
      thyroid carcinomas is not clear. We sought to relate HLA alleles to
      susceptibility to papillary thyroid carcinoma (PTC) and also to clinical and
      pathological characteristics of PTC patients. DESIGN AND PATIENTS: The
      distribution of HLA in 181 unrelated Caucasian patients with PTC was compared to
      the HLA distribution in 315 normal controls, 31 patients with follicular
      carcinoma (FTC), 29 patients with lymphocytic thyroiditis (LT) and 50 patients
      with multinodular goitre (MNG), using a microlymphocytotoxicity assay. RESULTS:
      Compared to normal controls, patients with PTC showed a significantly increased
      frequency of HLA-DQ4 [12.8%vs. 3.5%, P=0.0005, P(corrected) (P(c))=0.0032, odds
      ratio (OR)=4.058, 95% confidence interval (95% CI)=1.820-9.045] and HLA-DR8
      (10.9%vs. 4.3%, P=0.013, P(c) > 0.05, OR=2.752, 95% CI=1.275-5.940). DQ4 and DR8
      were also significantly increased in patients with MNG (DQ4, 16.3%; DR8, 16.3%)
      compared to controls (DQ4, P=0.0019, P(c)=0.011, OR=5.420, 95% CI=1.978-14.852;
      DR8, P=0.0044, P(c)=0.062). Linkage disequilibrium (LD) for these two alleles was
      present in controls (D=0.0130, P=9.7e-57) and in MNG patients (D=0.0730, P=4.6e
      19) but not in PTC patients (D=0.038, P>0.05). In the subgroup of PTC subjects
      with concomitant 0thyroidal neoplasias (n=27), there was a significant (P< 0.05)
      increase in the frequency of B57 (18.5%), DR11 (56.5%) and DQ3 (81.8%) compared
      to PTC patients without coexistent neoplasias (2.0%, 21% and 47%, respectively).
      No significant differences of HLA allele distribution was found in relation to
      PTC histology, age at diagnosis (> 45 or <or45 years), gender or tumour-node
      metastasis (TNM) staging. In patients with FTC, the frequency of DR17 (FTC=51.6%;
      controls =; P=0.0009; P(c)=0.0138) was significantly increased compared to
      controls. Patients with LT showed a higher frequency of the DR11 allele (48.3%)
      than controls (DR11=21.3%; P=0.0028, P(c)=0.039, OR=3.445, 95% CI=1.568-7.567).
      CONCLUSIONS: We have typed the largest series of patients with thyroid carcinomas
      reported to date, and found that DR8 and DQ4 are independent susceptibility
      markers for PTC.

PMID- 16430718
TI  - Magnetic resonance imaging, clinical manifestations, and management of Rathke's
      cleft cyst.
AB  - OBJECTIVE: The management of Rathke's cleft cyst (RCC), particularly in patients
      with no symptoms or with only minor endocrinopathies, has not yet been
      established. We retrospectively analysed patients with RCC to elucidate
      correlations between the clinical manifestations, magnetic resonance imaging
      (MRI) findings, histology and therapeutic outcomes. METHODS: We retrospectively
      studied 37 patients with RCC, who underwent computed tomography (CT), MRI and
      endocrinological examinations, of whom 27 patients underwent surgical
      intervention. RESULTS: The presence of frontal headaches and anterior pituitary
      dysfunction was unrelated to the cyst size but was more frequent in patients with
      high- and isointensity cysts on T1-weighted images (WIs) than those with low
      intensity cysts (P=0.0159 and P=0.0249, respectively). All three patients with
      posterior pituitary dysfunction had a high-intensity cyst on T1-WI (P=0.0385),
      whereas pituitary dysfunction was not observed in patients with a low-intensity
      cyst on T1-WI. In contrast to the excellent therapeutic outcomes with regard to
      visual disturbance and hyperprolactinaemia, recovery of pituitary dysfunction was
      rare; only three of nine patients with hypopituitarism showed improvement. Among
      six patients with histologically recognized intense chronic inflammation in the
      cyst wall, five patients had an RCC of T1 high intensity (P=0.0161), two patients
      had distinct rim enhancement on MRI (P=0.0060), all patients had frontal
      headaches (P=0.0130), and four patients had associated hypopituitarism
      (P=0.0243), none of which improved after surgical intervention. CONCLUSION: RCCs
      of high- and isointensity on T1-weighted images, which contain mucous material
      within the cyst, may be associated with chronic inflammation that can potentially
      cause irreversible endocrine dysfunction. In asymptomatic patients with RCCs of
      these MR intensities, close follow-up with precise endocrinological evaluation
      and gadolinium-enhanced MRI is necessary to avoid occult progression of the
      inflammation.

PMID- 16430719
TI  - Increase of interferon-gamma-inducible CXC chemokine CXCL10 serum levels in
      patients with active Graves' disease, and modulation by methimazole therapy.
AB  - BACKGROUND: CXCL10 plays an important role in the initial phases of Graves'
      disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum
      levels (sCXCL10) in patients with GD have never been evaluated in relation to
      thyroid function and treatment. OBJECTIVE: To evaluate sCXCL10 in GD. DESIGN:
      Cross-sectional. PATIENTS: One hundred and three GD, 164 AT, 20 nontoxic
      multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70
      healthy controls (age- and sex-matched). MEASUREMENTS: We measured sCXCL10 in
      patients and controls, to relate this parameter to the clinical phenotype.
      RESULTS: Mean sCXCL10 in GD and AT patients were comparable (122+/-81 and 133+/
      102 pg/ml) and significantly higher (P<0.01) than in controls or NTMNG patients
      (73+/- 32 and 76+/- 25 pg/ml, respectively). Hyperthyroid GD had significantly
      higher sCXCL10 than euthyroid or hypothyroid GD (145+/- 92, 107+/- 56 and 105+/-
      46 pg/ml, respectively; P=0.01). GD patients with untreated hyperthyroidism had
      higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI)
      treatment (166+/-125, 124+/- 41 and 94+/- 35 pg/ml, respectively; P=0.006).
      Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid
      GD patients with respect to untreated patients with relapse of hyperthyroidism
      after a previous MMI course (176+/-125, 155+/- 97 pg/ml, respectively). GD had
      similar sCXCL10 to AT and higher than TNG patients or controls (all age- and sex
      matched) (144+/- 81, 149+/- 114, 101+/- 27 and 86+/- 44 pg/ml, respectively;
      P=0.02). CONCLUSIONS: sCXCL10 is associated with the active phase of GD in both
      newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in
      treated patients with GD may be related to the immunomodulatory effects of MMI.

PMID- 16430720
TI  - Tissue levels of adiponectin, tumour necrosis factor-alpha, soluble intercellular
      adhesion molecule-1 and heart-type fatty acid-binding protein in human coronary
      atherosclerotic plaques.
AB  - BACKGROUND: There is little information available about any link between the
      levels of adiponectin, intercellular adhesion molecule-1 (ICAM-1), tumour
      necrosis factor-alpha (TNF-alpha) and heart-type fatty acid-binding protein (H
      FABP) in coronary atherosclerotic plaque specimens. AIM: To analyse tissue levels
      of adiponectin, ICAM-1, TNF-alpha and H-FABP in the plaques obtained from
      coronary artery bypass grafting (CABG) and to evaluate whether there is any
      relationship between these variables and other characteristics. PATIENTS AND
      METHODS: Coronary artery specimens from 37 consecutive patients (28 men and nine
      women) at time of CABG procedure and preprocedural blood samples were obtained.
      Tissue concentrations of adiponectin, ICAM-1, TNF-alpha and H-FABP in the
      atherosclerotic plaques were measured. RESULTS: Blood glucose and tissue levels
      of TNF-alpha and ICAM-1 were negatively correlated with tissue levels of
      adiponectin, whereas TNF-alpha was positively correlated with ICAM-1 in
      atherosclerotic plaques. In addition, there was a positive correlation between
      blood glucose and tissue levels of both TNF-alpha and ICAM-1. TNF-alpha and ICAM
      1 levels in atherosclerotic plaques appear to progressively increase whereas
      adiponectin levels progressively decrease with smoking status. Atherosclerotic
      tissue levels of these substances are also altered in diabetes. CONCLUSIONS: The
      data are in accord with those in prior publications on the detection and
      quantification of various inflammatory cytokines in atherosclerotic plaques. Our
      results indicate that diabetic state and smoking, in addition to other
      physiopathological mechanisms, may create a chronic inflammatory situation in the
      atherosclerotic process.

PMID- 16430722
TI  - Effectiveness and tolerability of 3-year lanreotide Autogel treatment in patients
      with acromegaly.
AB  - OBJECTIVE: During short-term treatment, monthly subcutaneous injections of
      lanreotide Autogel are effective in controlling GH/IGF-1 hypersecretion and are
      well tolerated in patients with acromegaly. This study reports the effectiveness
      and the tolerability of lanreotide Autogel for at least 3 years in acromegalic
      patients. PATIENTS: Fourteen patients (nine females, five males) were treated
      with titrated doses of lanreotide Autogel. DESIGN: This clinical study was an
      extension of a previous trial. After three fixed-dose lanreotide Autogel
      injections, treatment was adjusted according to mean GH and IGF-I levels. After 3
      years of treatment, patients were receiving 120 (n=7), 90 (n=2) and 60 mg (n=4)
      monthly injections of lanreotide Autogel. MEASUREMENTS: Acromegalic symptoms, GH
      and IGF-1 concentrations were analysed at the end of lanreotide microparticle
      treatment, and after 4, 8, 12, 24, 30 and 36 months of lanreotide Autogel
      therapy. Tolerance and side-effects were monitored throughout the 3-year study.
      RESULTS Hormonal control (GH <or= 2.5 microg/l and age- and sex-normalized IGF-1)
      was achieved in six (46%) patients. With the exception of an unrelated death due
      to pulmonary embolism, no patient withdrew from study. The number of patients
      reporting digestive adverse events was seven (12 episodes) for the fixed-dose
      period, and four (eight episodes), two (six episodes) and one (three episodes) at
      the end of the first, second and third year of treatment, respectively.
      Persistent induration at the injection sites was reported by two patients, and
      histological findings were consistent with benign injection-site granulomas. New
      cholelithiasis or sludge occurred in five (35%) patients during the lanreotide
      Autogel treatment. CONCLUSION: This 3-year study shows that lanreotide Autogel is
      effective in controlling GH/IGF-1 hypersecretion and is well tolerated during
      long-term treatment of patients with acromegaly.

PMID- 16430721
TI  - The IGF-I system and the renal and haemodynamic effects of losartan in
      normotensive patients with type 2 diabetes mellitus: a randomized clinical trial.
AB  - OBJECTIVE: Losartan has been shown to protect the diabetic kidney, at least
      partly independent of changes in blood pressure. Imbalances in the IGF-I system
      are associated with the development of diabetic nephropathy. We investigated
      whether renal as well as haemodynamic effects of losartan are associated with
      changes in the IGF-I system in normotensive patients with type 2 diabetes
      mellitus (T2DM). DESIGN AND PATIENTS: This randomized, double-blind placebo
      controlled clinical trial involved 74 normotensive patients with T2DM and
      microalbuminuria. Thirty-eight patients were assigned to receive losartan and 36
      patients were assigned to receive placebo for 10 weeks. MEASUREMENTS: Serum
      levels of total and free IGF-I, IGFBP-3, creatinine and haemoglobin A(1c)
      (HbA(1c)), as well as urinary albumin excretion rate, creatinine clearance and
      blood pressure, were measured prior to the start of treatment and after 10 weeks
      of treatment. RESULTS: At baseline, serum levels of IGFBP-3 were elevated and
      serum levels of free IGF-I were reduced. Losartan tended to reduce IGFBP-3 levels
      and to increase free IGF-I levels, although neither effect was statistically
      significant. These effects were more pronounced in a subanalysis of 18 losartan
      treated patients with stable metabolic parameters, with a decrease in IGFBP-3
      from 133.2 to 122.6 nmol/l (P=0.006) and an increase in free IGF-I levels by 8%
      (ns). Serum levels of total IGF-I were unaffected. The change in IGFBP-3 was
      inversely correlated to the change in creatinine clearance (r=-0.4; P=0.02).
      Total and free IGF-I inversely correlated to systolic blood pressure (r= -0.46;
      P=0.007 and r=0.26; P=0.14 respectively). Furthermore, changes in total IGF-I and
      IGFBP-3 correlated to changes in serum creatinine levels in the metabolically
      stable patients (r=0.58, P=0.02 and r=0.6, P=0.01, respectively). Changes in the
      IGF-I system were unrelated to a reduction in microalbuminuria associated with
      losartan. CONCLUSIONS: Losartan lowered the elevated levels of IGFBP-3, although
      only significantly in the metabolically stable patients. A tendency towards an
      increase in free IGF-I levels was also observed, but this change was small and
      not statistically significant. These changes were not related to reduction in
      microalbuminuria, but might contribute to effects of losartan on creatinine
      clearance and blood pressure of losartan in normotensive patients with T2DM.

PMID- 16430723
TI  - Low-dose ACTH (1 microg) salivary test: a potential alternative to the classical
      blood test.
AB  - OBJECTIVES: Salivary cortisol is unaffected by cortisol binding globulin (CBG)
      and hence allows CBG-related variations in serum total cortisol to be bypassed.
      We assessed whether or not salivary cortisol can be used for the low-dose (1
      microg) ACTH test in subjects with presumed normal and elevated levels of CBG.
      PATIENTS/METHODS: We measured serum and salivary cortisol responses to
      intravenous administration of 1 microg ACTH in 14 healthy volunteers, 14
      'hyperoestrogenic' women [in their first or early second trimester of pregnancy,
      using oral contraceptives (OC) or on hormone replacement therapy (HRT)] and 10
      patients with secondary hypoadrenalism. Cortisol levels were recorded before as
      well as 30 and 60 min (+30; +60 min) after ACTH administration. RESULTS: Baseline
      salivary cortisol did not differ significantly between the hypoadrenal and
      healthy patients (7.11+/-1.4 and 12.13+/-1.59 nmol/l; P=0.48) but there was a
      significant difference between hypoadrenal and hyperoestrogenic patients (18.94+/
      3.44 nmol/l; P=0.01). The largest difference between hypoadrenal patients and
      healthy individuals was observed at+30 min (9.16+/-2.8, 52.65+/-8.78 and 48.81+/-
      6.9 nmol/l, in the hypoadrenal, healthy and hyperoestrogenic patients,
      respectively; P< 0.05). At this time-point values< 24.28 nmol/l were found in all
      hypoadrenal patients and cortisol levels >or= 27.6 nmol/l were found in 26 out of
      28 healthy volunteers. ACTH-stimulated serum cortisol but not salivary cortisol
      was significantly higher in hyperoestrogenic women than in the healthy volunteers
      at either+30 or+60 min. CONCLUSIONS: The salivary low-dose ACTH test yields
      results that parallel the response of circulating cortisol to ACTH and may
      provide an alternative to the blood test, particularly in situations where
      increased CBG levels complicate the changes in serum cortisol levels.

PMID- 16430724
TI  - Effect of protracted treatment with rosiglitazone, a PPARgamma agonist, in
      patients with Cushing's disease.
AB  - OBJECTIVE: Cushing's disease, hypercortisolism due to a pituitary ACTH-secreting
      tumour, is a highly morbid illness as yet without effective medical therapy.
      Recent studies have demonstrated that peroxisome proliferator-activated receptor
      gamma (PPARgamma) agonists effectively suppress ACTH secretion in a murine
      tumoral corticotroph cell line, but the few studies conducted so far in patients
      with ACTH-secreting pituitary adenomas have yielded variable results. DESIGN: Ten
      patients with Cushing's disease were treated with 4-16 mg rosiglitazone p.o.
      daily for 1-8 months (median 3 months) and plasma ACTH and cortisol, urinary free
      cortisol (UFC), as well as parameters of insulin sensitivity, were recorded. An
      acute challenge with 8 mg rosiglitazone for 2 days preceded long-term
      rosiglitazone administration. RESULTS: The acute challenge with rosiglitazone did
      not significantly modify plasma ACTH and cortisol levels. During protracted
      treatment with rosiglitazone, four patients showed a persistent reduction in UFC
      levels (up to 24% of pretreatment values), achieving normalization in three. In
      the others, UFC as well as plasma ACTH and cortisol decrements were inscribed
      within wide, random oscillations indicating that disease activity was
      substantially unchanged. Insulin sensitivity was ameliorated in most patients,
      without relation to ACTH or cortisol secretion. Untoward effects, such as weight
      gain, oedema and worsening of ecchymoses, were reported in several patients.
      CONCLUSIONS: Although effective in a subset of patients, protracted rosiglitazone
      administration did not consistently restrain ACTH and cortisol secretion in
      patients with Cushing's disease. Further investigations are needed to fully
      define the therapeutic potential of PPARgamma agonists in this disorder.

PMID- 16430725
TI  - Radioiodine therapy and age at menopause in patients with thyroid cancer.

PMID- 16430726
TI  - Three decades of clinical follow-up in 271 women with hyperprolactinaemia;
      macroprolactinaemia should be considered.

PMID- 16430727
TI  - Only two amino acid substitutions of I236N and V237E in exon 6 are converted to
      the CYP21 gene in a Chinese patient with congenital adrenal hyperplasia.

PMID- 16430728
TI  - Development of a measure to assess the impact of epilepsy on people with an
      intellectual disability: the Glasgow Epilepsy Outcome Scale - Client version
      (GEOS-C).
AB  - BACKGROUND: Epilepsy is common in people with intellectual disability, yet
      clinicians and researchers seldom obtain information directly from the client.
      The development and preliminary validation of a novel measure for use with people
      with mild to moderate intellectual disabilities is described. METHODS: Focus
      group methods (6 groups; 24 participants) identified issues of concern, and
      qualitative analysis (NUD*IST) was applied to derive items and themes for a draft
      scale. Psychometric scale development techniques were then used in a pilot study
      and subsequent field-testing to investigate validity and reliability (n = 46).
      RESULTS: A total of 148 issues of concern was reduced initially to 52 and then to
      42 items using these methods. The derived scale comprised sub-scales reflecting
      (1) concerns about having seizures; (2) about injury; (3) about issues during;
      and (4) after seizures; (5) about medication; (6) about what people think; and
      (7) about daily life. Cronbach alpha for the Glasgow Epilepsy Outcome Scale -
      Client version (GEOS-C) was 0.92, and ranged from 0.64-0.81 for the sub-scales.
      Relatively weak associations (r <or= 0.40), between client and family carer,
      staff carer or clinician views, suggests that proxy reports are not good
      predictors of how people with epilepsy themselves are feeling. Preliminary
      validation suggests that the GEOS-C can discriminate on variables of clinical
      importance. CONCLUSIONS: The GEOS-C complements existing GEOS measures, can be
      completed in 5-15 min depending upon the level of support required, and may
      provide a valuable clinical and research tool. Further validational work and
      appraisal of sensitivity are required.

PMID- 16430729
TI  - The impact of behaviour problems on caregiver stress in young people with autism
      spectrum disorders.
AB  - BACKGROUND: The purpose of this study was to examine the correlates of caregiver
      stress in a large sample of young people with autism spectrum disorders (ASDs).
      Two main objectives were to: (1) disentangle the effects of behaviour problems
      and level of functioning on caregiver stress; and (2) measure the stability of
      behaviour problems and caregiver stress. METHODS: Parents or teachers of 293
      young people with ASDs completed measures of stress, behaviour problems and
      social competence. Parents also completed an adaptive behaviour scale. Eighty-one
      young people were rated twice at a 1-year interval. RESULTS: Parents and teachers
      did not perfectly agree on the nature and severity of behaviour problems.
      However, both sets of ratings indicated that behaviour problems were strongly
      associated with stress. Conduct problems in particular were significant
      predictors of stress. Adaptive skills were not significantly associated with
      caregiver stress. Parental reports of behaviour problems and stress were quite
      stable over the 1-year interval, much more so than teacher reports. Parent
      ratings suggested that behaviour problems and stress exacerbated each other over
      time. This transactional model did not fit the teacher data. CONCLUSION: Results
      of this study suggested that it is a specific group of externalized behaviours
      that are the most strongly associated with both parent and teacher stress.
      Results were discussed from methodological and conceptual perspectives.

PMID- 16430730
TI  - Syndrome specificity and behavioural disorders in young adults with intellectual
      disability: cultural differences in family impact.
AB  - BACKGROUND: This study examined whether behaviour problems and adaptive behaviour
      of low functioning young adults, and well-being of their families, varied by
      diagnostic syndrome [intellectual disability (ID) only, cerebral palsy, Down
      syndrome, autism], as well as by cultural group. METHODS: Behaviour disorders in
      young adults with moderate to severe ID were assessed from information provided
      by 282 caregivers during in-home interviews. The sample consisted of 150 Anglo
      participants, and 132 Latino, primarily Spanish-speaking, participants drawn from
      Southern California. RESULTS: Behaviour disorders and maternal well-being showed
      the same pattern across disability syndromes. Autism was associated with the
      highest scores in multiple behaviour problem areas as well as maternal reports of
      lower well-being. Down syndrome was associated with the lowest behaviour problem
      scores and the highest maternal well-being. When behaviour problems were
      controlled for, diagnostic groups accounted for no additional variance in
      maternal stress or depression. The pattern of behaviour problems and well-being
      did not differ by sample (Anglo vs. Latino), although level on well-being
      measures did. Latina mothers reported significantly higher depression symptoms
      and lower morale, but also higher positive impact from their child than did Anglo
      mothers. CONCLUSIONS: Caregivers of young adults with autism report more
      maladaptive behaviour problems and lower personal well-being, or stress, relative
      to other diagnostic groups, regardless of cultural group. However, cultural
      differences exist in caregiver reports of depression, morale, and positive
      perceptions. Implications for service provision aimed at families of children
      with challenging behaviour problems are discussed in the context of culture.

PMID- 16430731
TI  - The response to challenging behaviour by care staff: emotional responses,
      attributions of cause and observations of practice.
AB  - BACKGROUND: Previous studies have attempted to apply Weiner's attributional model
      of helping behaviour to care staff who work with service users with intellectual
      disabilities and challenging behaviours by using studies based on vignettes. The
      aims of the current study were to investigate the application of Weiner's model
      to 'real' service users with intellectual disabilities and challenging behaviours
      and to observe the care staff's actual responses to challenging behaviours
      displayed by service users. Also, to compare care staff attributions, emotions,
      optimism, willingness to help and observed helping behaviours for self-injurious
      behaviours in comparison to other forms of challenging behaviours. METHOD: A
      total of 27 care staff completed two sets of measures, one set regarding a self
      injurious behaviour and the other regarding other forms of challenging behaviour.
      An additional 16 staff completed one set of measures. The measures focused on
      care staff attributions, emotions, optimism and willingness to help. Also, 16 of
      the care staff were observed interacting with the service users to collect data
      regarding their responses to challenging behaviours. RESULTS: For both self
      injurious behaviours and other forms of challenging behaviour, associations were
      found between the care staff internal, stable and uncontrollable attribution
      scores and care staff negative emotion scores. However, no associations were
      found between the care staff levels of emotion, optimism and willingness to help.
      Some associations were found between the care staff levels of willingness to help
      and observed helping behaviours. There were significant differences between the
      care staff attribution scores with higher scores being obtained for
      uncontrollable and stable attributions for other forms of challenging behaviours.
      No significant differences were found between the care staff emotions, optimism,
      willingness to help and observed helping behaviours. CONCLUSIONS: The results did
      not provide support for Weiner's attributional model of helping behaviour.
      However, a preliminary model of negative care staff behaviour was derived from
      the exploratory analyses completed. This model proposes that there are
      associations between internal, stable and uncontrollable attributions and
      negative emotions in care staff and also between negative emotions and negative
      behaviours displayed by care staff in response to the actions of service users.

PMID- 16430732
TI  - Empowering words, disempowering actions: an analysis of interactions between
      staff members and people with learning disabilities in residents' meetings.
AB  - BACKGROUND: This study examined power dynamics in verbal interactions between
      care staff and people with learning disabilities. METHOD: Recordings of
      residents' meetings in a group home for people with learning disabilities were
      examined. RESULTS: The analysis showed some of the ways in which power was
      exercised in verbal interactions between care staff and residents. It was found
      that staff adopted various techniques to guide the discussion and produce certain
      kinds of statements and decisions. It could be said that in these cases, the
      staff were having to decide between two or more conflicting institutional
      objectives. CONCLUSION: The effect was that staff contributions sometimes
      produced interactional patterns which were contrary to the goal of encouraging
      the residents to speak up and have more say in the management of their home.

PMID- 16430735
TI  - Molecular pathology of odontogenic tumors.
AB  - Odontogenic tumors are lesions derived from the elements of the tooth-forming
      apparatus and are found exclusively within the jawbones. This review represents a
      contemporary outline of our current understanding of the molecular and genetic
      alterations associated with the development and progression of odontogenic
      tumors, including oncogenes, tumor-suppressor genes, oncoviruses, growth factors,
      telomerase, cell cycle regulators, apoptosis-related factors, regulators of tooth
      development, hard tissue-related proteins, cell adhesion molecules, matrix
      degrading proteinases, angiogenic factors, and osteolytic cytokines. It is hoped
      that better understanding of related molecular mechanisms will help to predict
      the course of odontogenic tumors and lead to the development of new therapeutic
      concepts for their management.

PMID- 16430733
TI  - Adult persons with intellectual disabilities on the island of Ireland.
AB  - BACKGROUND: Information on the numbers of adult persons (aged 20 years and over)
      with intellectual disability (ID) is rarely collated at a national level. This is
      an impediment to service planning especially for a changing population. METHODS:
      A database of all persons in receipt of ID services has been operating in the
      Republic of Ireland since 1995. In Northern Ireland, regional databases can be
      used to provide similar information. RESULTS: A total of 25,134 persons were
      known to services in 2002; an overall prevalence for the island of 6.34 per
      1,000. However this rate varied for different age groupings and across the two
      parts of the island. General population characteristics, as well as service
      factors, appear to account for this. Significantly more people lived with family
      carers in Northern Ireland. By 2021, it was estimated that the population would
      increase by over 20% with around one-third of persons aged over 50 years.
      CONCLUSIONS: These data illustrate the variations that exist in the numbers of
      adult persons with ID known to services across and within regions of a country.
      Hence caution must be exercised in extrapolating prevalence rates derived in one
      area to another. The availability of comparative national data highlights issues
      around the equitable funding and delivery of services.

PMID- 16430736
TI  - Immunohistochemical analysis of the biological potential of odontogenic
      keratocysts.
AB  - BACKGROUND: The aim of this study was to analyse the usefulness of detecting
      important apoptosis and proliferation markers in assessing the biological
      potential of odontogenic keratocysts (OKC) and thus selecting the optimal
      diagnostic algorithm for these lesions. METHODS: Indirect immunohistochemistry
      and relevant statistical methods were used for analysis of formalin-fixed and
      paraffin-embedded samples from 98 patients. RESULTS: Nevoid basal cell carcinoma
      syndrome (NBCCS) keratocysts were characterized by higher expression of Bcl-2,
      p27Kip1 and c-erbB-2 as well as by lower proliferative activity measured by Ki-67
      in basal cell epithelium and by a lower inflammatory response in comparison with
      sporadic keratocysts. Dentigerous, radicular and non-specified odontogenic cysts
      differed from both NBCCS and sporadic keratocysts in a wide spectrum of apoptosis
      and/or cell cycle-related protein expressions, higher proliferation in the basal
      cell layer, and vice versa, lower proliferation in the suprabasal cell layer.
      CONCLUSIONS: The NBCCS keratocysts have a different immunophenotype from sporadic
      keratocysts and both types are distinguishable from dentigerous, radicular and
      non-specified odontogenic cysts. These findings confirm the separate biological
      potential of these lesions and the results of the immunohistochemical analysis
      have diagnostic and prognostic implications.

PMID- 16430737
TI  - Histopathological changes in oral mucosa due to takhzeen al-qat: a study of 70
      biopsies.
AB  - BACKGROUND: Chewing qat leaves (takhzeen al-qat) is a common habit in East Africa
      and Yemen. It has been reported to cause different systemic effects. At the oral
      mucosa, it causes clinical changes that appear as white lesions. The aim of this
      paper was to study the histopathological changes in the oral mucosa related to
      takhzeen al-qat. METHOD: Seventy biopsies were studied. Biopsies were divided
      into three groups: (G1) Forty biopsies were taken from the oral mucosa of the
      chewing side. (G2) Twenty biopsies were taken from the oral mucosa of the
      opposite side and (G3) 10 biopsies were taken from the oral mucosa of non-chewing
      volunteers. All biopsies were conventionally prepared, paraffin embedded and
      histopathological protocol was followed for each case to study the
      histopathological changes. RESULTS: Acanthosis appeared in 97.5% (G1) and 50%
      (G2), parakeratosis in 45% (G1) and 0% (G2), orthokeratosis in 25% (G1) and 10%
      (G2), abnormal rete ridges in 97.5% (G1) and 25% (G2), intracellular edema in 80%
      (G1) and 65% (G2), inflammatory infiltration in the subjacent connective tissue
      of 55% (G1) and 5% (G2), increased amount of collagenous fibers in 47.5% (G1) and
      0% (G2), and mild epithelial dysplasia in 25% (G1) and 0% (G2). Biopsies taken
      from G3 showed no histopathological changes except one case with intracellular
      edema. Differences were statistically significant. CONCLUSION: Takhzeen al-qat
      caused histopathological changes in the oral mucosa at the side of chewing;
      however, these changes were innocuous and without any evidence of malignancy.

PMID- 16430738
TI  - HPV detection in primary intra-oral squamous cell carcinomas--commensal,
      aetiological agent or contamination?
AB  - BACKGROUND: High-risk human papilloma viruses (HPV) are reported to be
      significant independent risk factors for oral squamous cell carcinoma (OSCC). The
      prevalence of HPV in OSCC in a South African population sample was evaluated
      comparing three different HPV detection methods. METHODS: Tumour and adjacent
      morphologically normal oral mucosa of 59 resections of primary OSCC were
      evaluated for the presence of HPV using real-time polymerase chain reaction
      (PCR), conventional in situ hybridization (ISH), and a signal amplification ISH
      technique (Dako GenPoint). RESULTS: HPV18 DNA was detected in seven cases using
      real-time PCR. No positivity was found with the other two ISH techniques.
      CONCLUSIONS: We support the view that HPV is probably unimportant in the
      pathogenesis of OSCC and hypothesize HPV detection techniques as the main reason
      for the positive results in many studies. Real-time PCR was confirmed as the most
      sensitive technique, but researchers are urged to incorporate strict internal
      controls when using this detection method.

PMID- 16430739
TI  - Relationship between TNF-alpha and TUNEL-positive chondrocytes in antigen-induced
      arthritis of the rabbit temporomandibular joint.
AB  - BACKGROUND: Terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate biotin nick end-labeling (TUNEL) staining is a widely accepted
      method for the detection of DNA fragmentation in nuclei of apoptotic cells. Tumor
      necrosis factor (TNF)-alpha is closely associated with changes in condylar
      cartilage and modulates apoptosis in various tissues including cartilage. The aim
      of this study was to investigate the relationship between apoptotic chondrocytes
      and TNF-alpha in a rabbit model of arthritis. METHOD: Unilateral
      temporomandibular joint (TMJ) arthritis was induced in 20 adult New Zealand White
      rabbits. From 1 day to 6 weeks after the induction of arthritis,
      immunohistochemical analysis for TNF-alpha and TUNEL was performed. RESULTS: In
      condylar cartilage, TNF-alpha-positive cells and TUNEL-positive cells were
      localized together. TNF-alpha-positive chondrocytes seemed to precede TUNEL
      positive cells. CONCLUSIONS: The results of the present study suggest that TNF
      alpha may be involved in apoptosis and/or apoptotic necrosis of chondrocytes as
      TMJ arthritis progresses from the acute to chronic stage.

PMID- 16430740
TI  - The functional (-1171 5A-->6A) polymorphisms of matrix metalloproteinase 3 gene
      as a risk factor for oral submucous fibrosis among male areca users.
AB  - BACKGROUND: Insertion/deletion (-1171 5A-->6A) polymorphisms in the promoter
      region of matrix metalloproteinase 3 (MMP3) gene result in different
      transcriptional activities. MMP3 is able to degrade collagens types II, V, IX,
      and X, and other extracellular matrix. The functional promoter polymorphism of
      MMP3 has been related to the susceptibility in some inflammatory diseases and
      metastasis of cancers. METHODS: Oral submucous fibrosis (OSF) and oral squamous
      cell carcinoma (OSCC) are prevalent among Asian areca users. In this study,
      genomic DNA obtained from the blood of OSCC (n = 150), OSF (n = 71), and control
      non-diseased areca user (n = 98) in male were subjected to polymerase chain
      reaction (PCR)-based genotyping of MMP3. RESULTS: The 5A genotype in MMP3
      promoter was observed more frequently in OSF group than in control group (P =
      0.01). No significant difference was noted between OSCC and control groups on the
      5A genotype frequency (P = 0.18). No association was found between 5A genotype in
      MMP3 promoter and site or lymph node metastasis and stage of OSCC. CONCLUSION:
      The results indicated that the 5A genotype of MMP3 promoter was associated with
      the risk of OSF but not OSCC.

PMID- 16430741
TI  - Isolation and characterization of synovial cells from the human temporomandibular
      joint.
AB  - BACKGROUND: The synovial tissues with temporomandibular disorders (TMDs) often
      show chronic inflammatory changes and the synovial cells participate in the
      pathogenic processes of TMDs. The synovial membrane is composed of a synovial
      lining layer and a connective sublining layer. The synovial lining layer is made
      up of two kinds of cells: macrophage-like type A and fibroblastic type B cells.
      The aim of this study was to isolate and characterize synovial cells from the
      human temporomandibular joint (TMJ). METHODS: Synovial cells were isolated using
      an explant culture method. Then, we characterized the cultured synovial cells
      (SGA2 cells) using immunocytochemistry. RESULTS: SGA2 cells expressed the
      fibroblastic markers vimentin and prolyl 4-hydroxylase; they also expressed
      laminin and heat shock protein 27, all of which are markers of type B cells.
      However, some cells expressed the macrophage marker CD68. These CD68-positive
      cells simultaneously expressed laminin. CONCLUSIONS: We isolated and cultured
      synovial type B cells from the human TMJ, and identified the presence of
      intermediate type synovial lining cells, having the phenotypic properties of both
      type A and type B cells, among the synovial lining cells.

PMID- 16430742
TI  - Levamisole can modulate the serum tumor necrosis factor-alpha level in patients
      with recurrent aphthous ulcerations.
AB  - BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory
      lesions. Tumor necrosis factor (TNF)-alpha is an important inflammatory mediator
      and a critical cytokine for adequate host defense. Our previous studies have
      shown that 14-43% and 59-63% of patients in the ulcerative stage of major, minor
      or herpetiform RAU have significantly higher than normal serum levels of
      interleukin (IL)-6 and IL-8, respectively. In this study, we examined whether RAU
      patients in the ulcerative stage had a significantly higher than normal serum
      level of TNF-alpha and assessed whether treatment with levamisole can modulate
      serum TNF-alpha levels in RAU patients. METHODS: This study used a solid phase,
      two-site sequential chemiluminescent immunometric assay to determine the baseline
      serum levels of TNF-alpha in 146 patients with RAU, nine patients with traumatic
      ulcers (TU), and 54 normal control subjects. Fifty-five RAU patients with serum
      TNF-alpha levels higher than 5.0 pg/ml were treated with levamisole for 0.5-4
      months and their serum TNF-alpha levels were measured after treatment. RESULTS:
      We found that 29% (42 of 146) RAU patients as well as 39% (24 of 61) major type,
      20% (14 of 69) minor type, and 25% (four of 16) herpetiform type RAU patients had
      a serum level of TNF-alpha greater than the upper normal limit of 7.4 pg/ml. The
      mean serum level of TNF-alpha in patients with RAU (9.1 +/- 1.0 pg/ml, P <
      0.001), major type RAU (11.6 +/- 1.9 pg/ml, P < 0.001), minor type RAU (6.9 +/-
      0.9 pg/ml, P < 0.005), or herpetiform type RAU (9.6 +/- 2.7 pg/ml, P < 0.001) was
      higher than that (3.8 +/- 0.2 pg/ml) in normal control subjects. The mean serum
      TNF-alpha level was significantly higher in patients with major type RAU than in
      patients with minor type RAU (P < 0.05) and was significantly higher in major
      type RAU patients in the exacerbation stage than in the post-exacerbation stage
      (P < 0.05). In 55 RAU patients with serum TNF-alpha levels higher than 5.0 pg/ml,
      treatment with levamisole for a period of 0.5-4 months could significantly reduce
      the serum TNF-alpha level from 16.4 +/- 1.9 to 5.8 +/- 0.6 pg/ml (P < 0.001).
      CONCLUSIONS: We conclude that a significantly higher than normal serum level of
      TNF-alpha can be detected in 20-39% of patients in the ulcerative stage of major,
      minor or herpetiform RAU. The serum TNF-alpha level may be associated with the
      severity and the stage of RAU. Levamisole can modulate serum TNF-alpha levels in
      RAU patients.

PMID- 16430743
TI  - The efficacy of amlexanox OraDisc on the prevention of recurrent minor aphthous
      ulceration.
AB  - BACKGROUND: The study was designed to determine the efficacy of OraDisc (active
      component 2 mg amlexanox) on the prevention of aphthous ulcers treated at the
      prodromal stage. METHODS: Thermographic imaging was used to confirm the presence
      of a prodromal ulcer. Fifty-two patients were randomized to receive OraDisc (N =
      26) or vehicle patches (N = 26). Patches were applied four times a day for 72 h
      over the prodromal area. The percentage of subjects who developed an ulcer at 72
      h was compared between groups using the Fisher's exact test. RESULTS: About 50%
      of subjects in the OraDisc group developed an ulcer by day 4 compared with 69% in
      the vehicle group. Erythema score, ulcer size, pain scores and thermographically
      active area and temperature all showed trends towards healing in the OraDisc
      group. CONCLUSION: The OraDisc prevents ulcers from developing when compared with
      the vehicle patch.

PMID- 16430744
TI  - Oral tuberculosis associated with a treatment with anti-rheumatic drugs.
AB  - BACKGROUND: The use of immunosuppressive medication is a dominant risk factor for
      infection in patients with rheumatoid arthritis (RA). Methotrexate (MTX) is one
      of the traditional disease-modifying antirheumatic drugs. Adalimumab [a human
      anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody] represent
      an important advance in the treatment of RA and has been recently come in use.
      TNF-alpha plays a role in the host defense against Mycobacterium tuberculosis and
      notably in granuloma formation. Infections occur at a high rate among those who
      use one or the combination of the two medications. METHOD: We examined a female
      patient that was referred to our department for evaluation and treatment of a
      granular lesion on the soft palate and uvula, complaining of mild dysphagia. The
      patient was treated for 4 months with MTX and adalimumab for RA before the oral
      lesion appeared. RESULTS: The histopathological examination of a specimen of the
      oral lesion, taken by biopsy, showed a chronic inflammation characterized by
      tuberculous granulomas. Polymerase chain reaction test and culture of a new
      specimen was positive for M. tuberculosis. CONCLUSIONS: The therapeutic use of
      MTX or/and adalimumab for the treatment of RA or few others diseases, can cause
      oral tuberculosis.

PMID- 16430745
TI  - Ectomesenchymal chondromyxoid tumor of the hard palate--a case report.
AB  - Ectomesenchymal chondromyxoid tumor (ECMT) is a rare tumor. Only 26 cases of ECMT
      have been reported, all occurred in the anterior tongue. We present a case of a
      30-year-old male with a nodule in the hard palate, which was reported as ECMT on
      histopathology. The differential diagnosis considered included are extraskeletal
      myxoid chondroma, ECMT, pleomorphic adenoma, oral focal mucinosis, chondroid
      choristoma, and ossifying fibromyxoid tumor. After serial sections no other
      component was observed and a diagnosis of ECMT was made by exclusion. The patient
      is asymptomatic on follow up. A review of existing literature is also presented
      here.

PMID- 16430746
TI  - Distance learning--meeting Africa's need for quality nursing care.

PMID- 16430753
TI  - Nursing and midwifery: Millennium Development Goals and the global human resource
      crisis.
AB  - The World Health Organization Global Advisory Group for Nurses and Midwives and
      wider stakeholders met in May 2005 against a background of concern over the
      disappointing progress being made towards the Millennium Development Goals
      (MDGs). The meeting considered the urgent need to address human resource issues,
      particularly those related to nursing and midwifery, if the MDGs are to be
      achieved.

PMID- 16430754
TI  - Primary health care nursing staff in Crete: an emerging profile.
AB  - BACKGROUND: In 2001, the newly established Regional Health and Welfare System of
      Crete commissioned the first needs' assessment study of nursing personnel
      employed in the public sector of primary health care (PHC). AIM: To capture the
      profile and professional needs of nursing staff working in Health Centers
      throughout the island of Crete and explore variations in nursing practice by
      educational preparation. METHODS: A newly developed, psychometrically tested
      questionnaire, was administered to all nursing staff in 14 rural Health Centers.
      FINDINGS: Vacancy rates are high, indicating a serious staffing deficit. The type
      of degree earned (2-year vs. 3 or 4-year program) does not differentiate nursing
      practice, with only two exceptions (obtaining a patient's history and counselling
      patients). The majority of respondents assess their existing knowledge and skills
      as 'adequate' while indicating a strong desire for continuing education. Job
      satisfaction is high in terms of interactions with clients and community
      recognition, while it is rated 'low' in terms of daily interactions with
      colleagues and support from work environment. CONCLUSION: Cretan nursing staff in
      PHC operate within a restricted and task-orientated framework. Their educational
      preparation has little effect in practice role variations and professional needs.
      The Regional Health and Welfare System of Crete should address daily supervision
      and support issues, on-the-job training, continuing education needs, while taking
      immediate action to avoid potential turnover of existing staff and to
      aggressively recruit young, qualified nursing staff who will choose a career in
      PHC nursing.

PMID- 16430755
TI  - Personal reflections on the 23rd Quadrennial Congress of the International
      Council of Nurses: 'Nursing on the move: knowledge, innovation and vitality'
      (Taipei Taiwan 21-27th May 2005).

PMID- 16430756
TI  - More than terminology: using ICNP to enhance nursing's visibility in Italy.
AB  - BACKGROUND: The International Council of Nurses (ICN) has elaborated an
      international terminology for nursing practice [International Classification of
      Nursing Practice (ICNP)] that can be useful to catalogue the problems of a
      nursing nature in diagnosis and also find a system for the classification of
      nursing activities. ICNP is also the reason why the Italian association
      Consociazione, representing Italian Nurses at ICN, through the School of Advanced
      Nursing of the University 'La Sapienza' of Rome, has set up a working group for
      the translation and experimentation of the ICNP version Beta 2. CONTENT: In this
      article the ICNP beta translation and validation into Italian is considered with
      some scenarios of how benefit could be derived by its utilization for nursing's
      visibility. The visibility of nursing care can be measured not only through
      patient outcomes but also by studying the existing data of patient care
      documentation. To have a common language and terminology in nursing is important
      for a universal understanding. RESULTS: Some philosophical reasoning on the
      genesis and development of ICNP is discussed along with arguments for and against
      nursing classification systems. Some findings on Italian experimentation for
      nursing documentation as well as economical analysis are reported along with a
      vision for future development and utilization.

PMID- 16430757
TI  - Dignified dying: phenomenon and actions among nurses in India.
AB  - PURPOSE: This study contributes to the ongoing efforts of the International
      Classification for Nursing Practice (ICNP) to describe the phenomenon of
      dignified dying, to describe nursing actions used to promote dignified dying, and
      to evaluate the validity of a dignified dying scale among practising nurses in
      India. DESIGN AND SAMPLE: This descriptive study surveyed 229 nurses who had
      cared for dying patients and were currently practising in government and private
      hospitals in India. METHODS: Nurses were recruited to complete a survey in either
      Hindi or English. The survey included demographic, open-ended questions, and a
      dignified dying scale of Likert-like items. Nurses also identified nursing
      interventions used in practice to promote dignified dying. FINDINGS: The
      descriptions of dignified dying phenomenon fit within the three major areas of
      the Dignity-Conserving Model of Care. A variety of interventions were reported,
      with more focusing on spiritual than physical factors. The 14 items selected
      reliably measured dignified dying, with a Cronbach's alpha of 0.79. Factor
      analysis yielded a 4-factor solution, with 11 items accounting for 56% of the
      variance. CONCLUSIONS: Nurses in India endorsed spirituality as an essential
      aspect of the phenomenon of dignified dying. Nursing actions to promote dignified
      dying supported finding spiritual comfort at end of life. These results
      contribute to an understanding of nursing phenomena and actions worldwide.

PMID- 16430758
TI  - Cultural competency and nursing care: an Australian perspective.
AB  - AIMS: To propose a process that will facilitate cultural competence in Australian
      nursing practice. BACKGROUND: Cultural diversity is a prominent feature of the
      Australian health system and is impacting significantly on nursing care quality.
      A fictitious, but typical clinical exemplar is profiled that identifies cultural
      insensitivity in care practices leading to poor quality outcomes for the health
      consumer and her family. Strategies are proposed that will reverse this practice
      and promote culturally competent nursing care and that locates overseas qualified
      nurses in this process. CONCLUSION: This paper contributes to nursing care
      quality internationally by articulating strategies to achieve cultural competence
      in practice. Nurses must pay attention to interpersonal relationships and develop
      respect for the health consumer's value systems and ways of being, in order to
      protect their rights and avoid the tendency to stereotype individuals from
      particular cultures. The expertise of qualified nurses from different cultures
      can greatly assist this process.

PMID- 16430759
TI  - Decision making in childbirth: the influence of traditional structures in a
      Ghanaian village.
AB  - BACKGROUND: The regional health administration of the Brong-Ahafo Region in Ghana
      identified that although informed about the advantages of both aspects of care,
      pregnant women made use of antenatal services but not of the supervised delivery.
      Quantitative studies have identified economic factors that influence the
      decisions of pregnant women. AIM: To describe and understand the traditional
      structures of childbirth in Kwame Danso/Ghana and to explore why the pregnant
      women do not make use of supervised deliveries in the modern institutions.
      METHODS: A mini-ethnographic study, using participant observation and
      ethnographic interviews. FINDINGS: Cultural and social factors have a significant
      influence on the decisions related to childbirth. One of the most important
      factors identified was that the responsible persons for decisions related to a
      delivery were the older female relatives, rather than the mothers themselves.
      Older females used rational judgements to weigh up the possibilities of risks,
      interests and advantages related to their cultural, spiritual and social system.
      Other factors were staff behaviour that was characterized as unfriendly and
      lacking for respect as to the living conditions and thinking of the pregnant
      women in the village. CONCLUSIONS: Ethnographic research provided an
      understanding of traditional structures that have an influence on the decisions
      and behaviour of the community related to childbirth. Appreciation of these
      structures enabled health promotion and structured health services to be
      delivered in a more culturally appropriate way.

PMID- 16430760
TI  - Nurses and nursing education in Ghana: creating collaborative opportunities.
AB  - AIM: This is a story intended to motivate the reader to become immersed in
      'verbal snapshots' depicting the reality of nursing in Ghana as experienced by
      the writer. Its purpose is to encourage dialogue and creative collaboration
      between nurse educators in radically different settings, which would serve to
      enrich all those involved. BACKGROUND: During the summer of 2003, a faculty
      member from the School of Nursing at Georgia Southern University (GSU) travelled
      to Africa to establish a relationship between GSU and a nursing school in Ghana,
      West Africa. This paper is based on the daily journal kept by that faculty member
      who engaged in clinical practice experiences as well as discussions with nursing
      educators in Ghana. Integrated in this subjective account are health data
      specific to Ghana. These serve to underscore health issues and situations of
      urgent concern in Ghana as well as to the global community, and which will assist
      in highlighting the potential contribution of such collaboration to strengthening
      the health system of the country. CONCLUSIONS: The outcome of the relationship
      established during this visit was intended to be a meaningful interchange of
      resources and experiences for both faculty and students at the two schools. It
      was successful in that regard. Funding is now being sought to enable further
      collaboration.

PMID- 16430761
TI  - Use of traditional healers and modern medicine in Ghana.
AB  - PURPOSE: To gain understanding of the use of traditional and modern medicine
      among the people in Ghana, West Africa. METHODS: Data were collected from nine
      participants using a semi-structured questionnaire developed by the researchers
      based on review of the literature. FINDINGS: Data analysis was performed manually
      using reduction methodology to develop broad themes. Findings indicated that
      choices in healthcare modalities by literate Ghanaians included either
      traditional or modern medicine, or blending of both. Strong influences on these
      choices were the level of education and related themes, influence of family and
      friends, and spiritual/religious beliefs. IMPLICATIONS: Findings indicate that
      traditional and modern medicines will always be part of Ghanaian healthcare
      delivery and efforts should be made to integrate traditional practitioners into
      the national healthcare delivery system.

PMID- 16430762
TI  - Hospital nurse administrators in Japan: a feminist dimensional analysis.
AB  - BACKGROUND: Nursing administration research is scarce in Japan during a time when
      health care is rapidly reforming and baccalaureate and graduate nursing
      programmes are rapidly developing. Additionally, nursing administration content
      relies heavily on Western and non-nursing theories, some of which have been
      criticized for male bias. PURPOSE: The purpose of this article is to present key
      findings from a qualitative study that explored the perspectives or viewpoints of
      16 Japanese senior female nurse administrators in hospitals in order to learn
      what was happening in their working situations and how they were managing. DESIGN
      AND METHODS: This feminist study used dimensional analysis strategies for data
      collection and analysis. Semi-structured, tape-recorded interviews were conducted
      by both researchers in Japanese, transcribed into Japanese, and translated into
      English. RESULTS AND DISCUSSION: The resulting explanatory matrix portrayed a
      story of 16 nurse administrators, most of whom were able successfully to enact a
      management role in a context of role ambiguity that was congruent with their
      relational values and beliefs. Important conditions influencing value-based role
      enactment included organization mission and purpose, organization structure,
      nurse-doctor relationships, participant-supervisor relationships, and personal
      attributes. Many participants were able to overcome barriers in these categories
      using strategies of tempered radicalism and consequently made positive
      organizational changes. CONCLUSIONS: Advanced formal education, better
      organizational support, and a raised consciousness among nurses that views nurses
      and midwives as equal partners with other professionals will enable Japanese
      nurse administrators to help advance patient-centred care and nursing development
      and empowerment.

PMID- 16430763
TI  - Professional competence: factors described by nurses as influencing their
      development.
AB  - AIM: To discuss the results of a study that explored factors that may influence
      competence development. BACKGROUND: Competence, a controversial issue in health
      care settings, affects many aspects of the nursing profession, including
      education, practice and management. Although a number of research and discussion
      papers have explored the issue, in particular the meaning and assessment of
      nursing competence, to date little research has explored factors identified by
      nurses themselves as influencing their development of professional competence.
      METHODS: A purposive sample of 27 registered nurses was recruited from two
      university-affiliated hospitals. Data collection was by tape-recorded semi
      structured interviews. Interviews were transcribed verbatim and analysed
      according to the qualitative methodology of content analysis. FINDINGS: Six
      descriptive categories were identified from the data: experience, opportunities,
      environment, personal characteristics, motivation and theoretical knowledge.
      CONCLUSIONS: The findings suggest that the factors influencing the process of
      developing professional competence in nursing extend across personal and extra
      personal domains. An understanding of these factors may enhance the ability of
      nursing managers and educators to enable student and qualified nurses to pursue
      effective competency development pathways to prepare them to provide a high
      standard of care. These findings, which may have important implications for
      nursing practice, management and education, are being further tested in a larger
      study.

PMID- 16430764
TI  - Critical thinking and learning styles of students in conventional and accelerated
      programmes.
AB  - AIM AND PURPOSE: To assess the difference between the predominant critical
      thinking disposition(s) and learning styles of nursing students in the
      conventional (Stream I) and the accelerated (Stream II) baccalaureate nursing
      education programmes. This study will be beneficial to students, faculty and
      institutions as it will help them to acquire better understanding of critical
      thinking potentials and learning styles of nurses, as well as the relationship
      between learning styles and critical thinking dispositions. METHOD: This was a
      descriptive correlational study. The convenience sample consisted of 80 Stream I
      and 50 Stream II students. The following instruments were used for data
      collection: The Learning Styles Inventory of Kolb and the California Critical
      Thinking Dispositions Inventory of Facione and Facione. Descriptive and
      inferential statistics were used to analyse the data. RESULTS: Overall, Stream II
      students were significantly more critical thinkers (P=0.000), inquisitive
      (P=0.000) and self-confident (P=0.002). The predominant learning styles of
      Streams I and II were the diverger and the converger, respectively, with no
      difference except in relation to their learning abilities, namely, concrete
      experience (P=0.017), in favour of Stream I. Further, the findings indicate a
      weak (range of r=0.209-0.328) though significant (range of P=0.017-0.000)
      correlation between learning abilities and various critical thinking
      dispositions.

PMID- 16430765
TI  - An open letter to the international nursing community asking: what are we going
      to do about it?

PMID- 16430766
TI  - PKD1 and PKD2 mutations in Slovenian families with autosomal dominant polycystic
      kidney disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetically
      heterogeneous disorder caused by mutations in at least two different loci. Prior
      to performing mutation screening, if DNA samples of sufficient number of family
      members are available, it is worthwhile to assign the gene involved in disease
      progression by the genetic linkage analysis. METHODS: We collected samples from
      36 Slovene ADPKD families and performed linkage analysis in 16 of them. Linkage
      was assessed by the use of microsatellite polymorphic markers, four in the case
      of PKD1 (KG8, AC2.5, CW3 and CW2) and five for PKD2 (D4S1534, D4S2929, D4S1542,
      D4S1563 and D4S423). Partial PKD1 mutation screening was undertaken by analysing
      exons 23 and 31-46 and PKD2 . RESULTS: Lod scores indicated linkage to PKD1 in
      six families and to PKD2 in two families. One family was linked to none and in
      seven families linkage to both genes was possible. Partial PKD1 mutation
      screening was performed in 33 patients (including 20 patients from the families
      where linkage analysis could not be performed). We analysed PKD2 in 2 patients
      where lod scores indicated linkage to PKD2 and in 7 families where linkage to
      both genes was possible. We detected six mutations and eight polymorphisms in
      PKD1 and one mutation and three polymorphisms in PKD2. CONCLUSION: In our study
      group of ADPKD patients we detected seven mutations: three frameshift, one
      missense, two nonsense and one putative splicing mutation. Three have been
      described previously and 4 are novel. Three newly described framesfift mutations
      in PKD1 seem to be associated with more severe clinical course of ADPKD.
      Previously described nonsense mutation in PKD2 seems to be associated with cysts
      in liver and milder clinical course.

PMID- 16430767
TI  - Hydrogen peroxide scavenging is not a virulence determinant in the pathogenesis
      of Haemophilus influenzae type b strain Eagan.
AB  - BACKGROUND: A potentially lethal flux of hydrogen peroxide (H2O2) is continuously
      generated during aerobic metabolism. It follows that aerobic organisms have
      equipped themselves with specific H2O2 dismutases and H2O2 reductases, of which
      catalase and the alkyl hydroperoxide reductase (AhpR) are the best-studied
      prokaryotic members. The sequenced Haemophilus influenzae Rd genome reveals one
      catalase, designated HktE, and no AhpR. However, Haemophilus influenzae type b
      strain Eagan (Hib), a causative agent of bacterial sepsis and meningitis in young
      children, disrupted in its hktE gene is not attenuated in virulence, and retains
      the ability to rapidly scavenge H2O2. This redundancy in H2O2-scavenging is
      accounted for by peroxidatic activity which specifically uses glutathione as the
      reducing substrate. RESULTS: We show here that inside acatalasaemic H. influenzae
      all of the residual peroxidatic activity is catalyzed by PGdx, a hybrid
      peroxiredoxin-glutaredoxin glutathione-dependent peroxidase. In vitro kinetic
      assays on crude hktE- pgdx- H. influenzae Rd extracts revealed the presence of
      NAD(P)H:peroxide oxidoreductase activity, which, however, appears to be
      physiologically insignificant because of its low affinity for H2O2 (Km = 1.1 mM).
      Hydroperoxidase-deficient hktE- pgdx- H. influenzae Rd showed a slightly affected
      aerobic growth phenotype in rich broth, while, in chemically defined medium,
      growth was completely inhibited by aerobic conditions, unless the medium
      contained an amino acid/vitamin supplement. To study the role of PGdx in
      virulence and to assess the requirement of H2O2-scavenging during the course of
      infection, both a pgdx single mutant and a pgdx/hktE double mutant of Hib were
      assayed for virulence in an infant rat model. The ability of both mutant strains
      to cause bacteremia was unaffected. CONCLUSION: Catalase (HktE) and a sole
      peroxidase (PGdx) account for the majority of scavenging of metabolically
      generated H2O2 in the H. influenzae cytoplasm. Growth experiments with
      hydroperoxidase-deficient hktE- pgdx- H. influenzae Rd suggest that the
      cytotoxicity inflicted by the continuous accumulation of H2O2 during aerobic
      growth brings about bacteriostasis rather than bacterial killing. Finally, H2O2
      scavenging is not a determinant of Hib virulence in the infant rat model of
      infection.

PMID- 16430769
TI  - Abulia following penetrating brain injury during endoscopic sinus surgery with
      disruption of the anterior cingulate circuit: case report.
AB  - BACKGROUND: It is common knowledge that the frontal lobes mediate complex human
      behavior and that damage to these regions can cause executive dysfunction,
      apathy, disinhibition and personality changes. However, it is less well known
      that subcortical structures such as the caudate and thalamus are part of
      functionally segregated fronto-subcortical circuits, that can also alter behavior
      after injury. CASE PRESENTATION We present a 57 year old woman who suffered
      penetrating brain injury during endoscopic sinus surgery causing right basal
      ganglia injury which resulted in an abulic syndrome. CONCLUSION: Abulia does not
      result solely from cortical injury but can occur after disruption anywhere in the
      anterior cingulate circuit--in the case of our patient, most prominently at the
      right caudate.

PMID- 16430768
TI  - A proposed metric for assessing the measurement quality of individual
      microarrays.
AB  - BACKGROUND: High-density microarray technology is increasingly applied to study
      gene expression levels on a large scale. Microarray experiments rely on several
      critical steps that may introduce error and uncertainty in analyses. These steps
      include mRNA sample extraction, amplification and labeling, hybridization, and
      scanning. In some cases this may be manifested as systematic spatial variation on
      the surface of microarray in which expression measurements within an individual
      array may vary as a function of geographic position on the array surface.
      RESULTS: We hypothesized that an index of the degree of spatiality of gene
      expression measurements associated with their physical geographic locations on an
      array could indicate the summary of the physical reliability of the microarray.
      We introduced a novel way to formulate this index using a statistical analysis
      tool. Our approach regressed gene expression intensity measurements on a
      polynomial response surface of the microarray's Cartesian coordinates. We
      demonstrated this method using a fixed model and presented results from real and
      simulated datasets. CONCLUSION: We demonstrated the potential of such a
      quantitative metric for assessing the reliability of individual arrays. Moreover,
      we showed that this procedure can be incorporated into laboratory practice as a
      means to set quality control specifications and as a tool to determine whether an
      array has sufficient quality to be retained in terms of spatial correlation of
      gene expression measurements.

PMID- 16430770
TI  - Orchiectomy or androgen receptor blockade attenuates baroreflex-mediated
      bradycardia in conscious rats.
AB  - BACKGROUND: Previous studies have shown that testosterone enhances baroreflex
      bradycardia. Therefore, conscious unrestrained rats were used to investigate the
      role of the androgen receptor in the testosterone-mediated modulation of
      baroreflex bradycardia. Androgen depletion (3 weeks), and androgen receptor
      blockade (20-24 h), were implemented to test the hypothesis that testosterone
      influences baroreflex bradycardia via its activity at the androgen receptor in
      male rats. Phenylephrine (1-16 microg kg(-1)) was used to assess baroreflex
      bradycardia. RESULTS: Androgen depletion attenuated baroreflex bradycardia (P <
      0.01). The antiandrogen flutamide (5, 15, or 30 mg kg(-1), s.c.) caused dose
      related attenuation of baroreflex bradycardia in spite of a significant (P <
      0.05) increase in serum testosterone. The latter did not lead to increased serum
      17beta-estradiol level. CONCLUSION: The data suggest: 1) Androgen depletion or
      adequate androgen receptor blockade attenuates baroreflex bradycardia. 2) The
      reflex increase in serum testosterone may counterbalance the action of the lower
      doses (5 or 15 mg kg(-1)) of flutamide. 3) The absence of a change in serum
      17beta-estradiol rules out its contribution to flutamide action on baroreflex
      bradycardia.

PMID- 16430771
TI  - Expression of hepatoma-derived growth factor family members in the adult central
      nervous system.
AB  - BACKGROUND: Hepatoma-derived growth factor (HDGF) belongs to a polypeptide family
      containing five additional members called HDGF related proteins 1-4 (HRP-1 to -4)
      and Lens epithelial derived growth factor. Whereas some family members such as
      HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others
      is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the
      nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in
      the central nervous system of adult rats on the cellular level by
      immunohistochemistry. In addition we performed Western blot analysis of various
      brain regions as well as neuronal and glial cell cultures. RESULTS: HDGF was
      rather evenly expressed throughout all brain regions tested with the lowest
      expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus,
      prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the
      bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were
      found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast,
      strong expression of HRP-3 in the adult nervous system is restricted to neurons,
      except for very weak expression in oligodendrocytes in the brain stem. Although
      the majority of neurons are HRP-3 positive, some like cerebellar granule cells
      are negative. CONCLUSION: The coexpression of HDGF and HRP-2 in glia and neurons
      as well as the coexpression of all three proteins in many neurons suggests
      different functions of members of the HDGF protein family in cells of the central
      nervous system that might include proliferation as well as cell survival. In
      addition the restricted expression of HRP-3 point to a special function of this
      family member for neuronal cells.

PMID- 16430772
TI  - Selective regulation of MAP kinases and chemokine expression after ligation of
      ICAM-1 on human airway epithelial cells.
AB  - BACKGROUND: Intercellular adhesion molecule 1 (ICAM-1) is an immunoglobulin-like
      cell adhesion molecule expressed on the surface of multiple cell types, including
      airway epithelial cells. It has been documented that cross-linking ICAM-1 on the
      surface of leukocytes results in changes in cellular function through outside
      inside signaling; however, the effect of cross-linking ICAM-1 on the surface of
      airway epithelial cells is currently unknown. The objective of this study was to
      investigate whether or not cross-linking ICAM-1 on the surface of airway
      epithelial cells phosphorylated MAP kinases or stimulated chemokine expression
      and secretion. METHODS: The human lung adenocarcinoma (A549) cells and primary
      cultures of normal human bronchial epithelial (NHBE) cells were used in these
      studies. To increase ICAM-1 surface expression, cultures were stimulated with
      TNFalpha to enhance ICAM-1 surface expression. Following ICAM-1 upregulation,
      ICAM-1 was ligated with a murine anti-human ICAM-1 antibody and subsequently
      cross-linked with a secondary antibody (anti-mouse IgG(ab')2) in the presence or
      absence of the MAP kinase inhibitors. Following treatments, cultures were
      assessed for MAPK activation and chemokine gene expression and secretion. Control
      cultures were treated with murine IgG1 antibody or murine IgG1 antibody and anti
      mouse IgG(ab')2 to illustrate specificity. Data were analyzed for significance
      using a one-way analysis of variance (ANOVA) with Bonferroni post-test correction
      for multiple comparisons, and relative gene expression was analyzed using the 2
      DeltaDeltaCT method. RESULTS: ICAM-1 cross-linking selectively phosphorylated
      both ERK and JNK MAP kinases as detected by western blot analysis. In addition,
      cross-linking resulted in differential regulation of chemokine expression.
      Specifically, IL-8 mRNA and protein secretion was not altered by ICAM-1 cross
      linking, in contrast, RANTES mRNA and protein secretion was induced in both
      epithelial cultures. These events were specifically inhibited by the ERK
      inhibitor PD98059. Data indicates that ICAM-1 cross-linking stimulates a
      synergistic increase in TNFalpha-mediated RANTES production involving activation
      of ERK in airway epithelial cells. CONCLUSION: Results demonstrate that cytokine
      induced ICAM-1 on the surface of airway epithelial cells induce outside-inside
      signaling through cross-linking ICAM-1, selectively altering intracellular
      pathways and cytokine production. These results suggest that ICAM-1 cross-linking
      can contribute to inflammation in the lung via production of the chemokine
      RANTES.

PMID- 16430774
TI  - Hairy cell leukemia: a diagnosis by endoscopic ultrasound guided fine needle
      aspiration.
AB  - BACKGROUND: Endosonography (EUS) guided FNA is a relatively new imaging modality
      which is increasingly used for sampling deep-seated lymph nodes in the diagnosis
      and staging of various malignancies, both primary as well as metastatic. It is
      also useful for staging of non-Hodgkin's lymphoma as well as diagnosing
      recurrence. The diagnosis of leukemia on FNA samples from deep-seated
      lymphadenopathy poses an even greater challenge. Hairy cell leukemia (HCL) is an
      uncommon, but distinct, lympho-proliferative disorder of B cell origin. It
      usually affects the spleen and bone marrow and uncommonly involves lymph nodes.
      There are only a few cases reported where HCL was diagnosed on FNA specimens.
      CASE PRESENTATION: We report the first case of HCL accurately rendered on EUS-FNA
      samples. CONCLUSION: This report underscores the concept that the presence of a
      cytopathologist in the endoscopy suite plays an important role in providing
      accurate diagnoses of lymphoid lesions biopsied with EUS-FNA.

PMID- 16430773
TI  - The effect on behavior and bone mineral density of individualized bone mineral
      density feedback and educational interventions in premenopausal women: a
      randomized controlled trial [NCT00273260].
AB  - BACKGROUND: Limited information is available on ways to influence osteoporosis
      risk in premenopausal women. This study tested four hypotheses regarding the
      effects of individualized bone density (BMD) feedback and different educational
      interventions on osteoporosis preventive behavior and BMD in pre-menopausal
      women, namely: that women are more likely to change calcium intake and physical
      activity if their BMD is low; that group education will be more efficacious at
      changing behavior than an information leaflet; that BMD feedback and group
      education have independent effects on behavior and BMD; and, that women who
      improve their physical activity or calcium intake will have a change in bone mass
      over 2 years that is better than those who do not alter their behavior. METHODS:
      We performed a 2-year randomized controlled trial of BMD feedback according to T
      score and either an osteoporosis information leaflet or small group education in
      a population-based random sample of 470 healthy women aged 25-44 years (response
      rate 64%). Main outcome measures were dietary calcium intake, calcium supplement
      use, smoking behavior, physical activity, endurance fitness, lower limb strength
      and BMD. We used paired t-tests, one-way ANOVA and linear regression techniques
      for data analysis. RESULTS: Women who had feedback of low BMD had a greater
      increase in femoral neck BMD than those with normal BMD (1.6% p.a. vs. 0.7% p.a.,
      p = 0.0001), but there was no difference in lumbar spine BMD change between these
      groups (0.1% p.a. vs. 0.08% p.a., p = 0.9). Both educational interventions had
      similar increases in femoral neck BMD (Leaflet = +1.0% p.a., Osteoporosis self
      management course = + 1.3% p.a., p = 0.4). Femoral neck BMD change was only
      significantly associated with starting calcium supplements (1.3 % p.a, 95%CI
      +0.49, +2.17) and persistent self-reported change in physical activity levels
      (0.7% p.a., 95%CI +0.22, +1.22). CONCLUSION: Individualized BMD feedback combined
      with a minimal educational intervention is effective at increasing hip but not
      spine bone density in premenopausal women. The changes in behavior through which
      this was mediated are potentially important in the prevention of other diseases,
      thus measuring BMD at a young age may have substantial public health benefits,
      particularly if these changes are sustained.

PMID- 16430775
TI  - Nutrition rehabilitation of undernourished children utilizing Spiruline and
      Misola.
AB  - BACKGROUND: Malnutrition constitutes a public health problem throughout the world
      and particularly in developing countries. AIMS: The objective of the study is to
      assess the impact of an elementary integrator composed of Spiruline (Spirulina
      platensis) and Misola (millet, soja, peanut) produced at the Centre Medical St
      Camille (CMSC) of Ouagadougou, Burkina Faso, on the nutritional status of
      undernourished children. MATERIALS AND METHODS: 550 undernourished children of
      less than 5 years old were enrolled in this study, 455 showed severe marasma, 57
      marasma of medium severity and 38 kwashiorkor plus marasma. We divided the
      children randomly into four groups: 170 were given Misola (731 +/- 7 kcal/day),
      170 were given Spiruline plus traditional meals (748 +/- 6 kcal/day), 170 were
      given Spiruline plus Misola (767 +/- 5 kcal/day). Forty children received only
      traditional meals (722 +/- 8 kcal/day) and functioned as the control group. The
      duration of this study was eight weeks. RESULTS AND DISCUSSION: Anthropometrics
      and haematological parameters allowed us to appreciate both the nutritional and
      biological evolution of these children. The rehabilitation with Spiruline plus
      Misola (this association gave an energy intake of 767 +/- 5 kcal/day with a
      protein assumption of 33.3 +/- 1.2 g a day), both greater than Misola or
      Spiruline alone, seems to correct weight loss more quickly. CONCLUSION: Our
      results indicate that Misola, Spiruline plus traditional meals or Spiruline plus
      Misola are all a good food supplement for undernourished children, but the
      rehabilitation by Spiruline plus Misola seems synergically favour the nutrition
      rehabilitation better than the simple addition of protein and energy intake.

PMID- 16430776
TI  - Prognosis of screen-detected breast cancers: results of a population based study.
AB  - BACKGROUND: The reduced mortality rate from breast carcinoma among women offered
      screening mammography is demonstrated after 15-20 years of follow-up. However,
      the assessment of 5-year overall and event-free survival could represent an
      earlier measure of the efficacy of mammography screening program (MSP). METHODS:
      All cases of breast cancer diagnosed in the Province of Modena between years 1996
      and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer
      Registry (MCR). Stage of disease and treatment information were obtained from
      clinical records. All the events occurring up to June 30, 2003 were retrieved by
      experienced monitors. Five-year overall and event-free survival were the
      principal end-points of the study. RESULTS: During a 5-year period, 587 primary
      breast cancers were detected by the MSP and 471 primary breast cancers were
      diagnosed out of the MSP. The screen-detected breast cancers were smaller, more
      likely node negative, with low histological grade, low proliferative activity and
      positive receptors status. Furthermore, the breast cancer diagnosed through the
      MSP more frequently received a conservative surgery. The 5-year survival rate was
      94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The
      rate of 5-year event-free survival was 89% and 75% for the MSP participants and
      not participants, respectively (p = 0.0001). CONCLUSIONS: Our data confirm a
      favourable outcome of screen-detected breast cancers in terms of five-year
      overall and event-free survival, which reflect the good quality assurance
      parameters of the MSP. Finally, a cancer registry should be implemented in every
      area covered by screening programs.

PMID- 16430777
TI  - Angiomotin and angiomotin like proteins, their expression and correlation with
      angiogenesis and clinical outcome in human breast cancer.
AB  - BACKGROUND: Angiomotin is a newly discovered molecule that regulates the
      migration and tubule formation of endothelial cells. It therefore has been
      implicated in the control of angiogenesis under physiological and pathological
      conditions. This study examined the expression of angiomotin and its analogues,
      angiomotin-like 1 (L1) and -like 2 (L2) in breast tumour tissues, and analysed
      their correlation with angiogenesis and clinical outcomes. METHODS: Human breast
      tissues (normal n = 32 and tumours n = 120) were used. The levels of expression
      of angiomotin, L1 and L2 were determined using reverse transcription PCR.
      Microvessels were stained using antibodies against PECAM, von Willebrand factor
      (factor 8, or vWF) and VE-cadherin. The transcript levels of angiomotin and its
      analogues were assessed against the clinical and pathological background,
      including long term survival (120 months). RESULTS: Breast cancer tissues
      expressed significantly higher levels of angiomotin transcript, compared with
      normal mammary tissues (33.1 +/- 11 in normal versus 86.5 +/- 13.7 in tumour
      tissues, p = 0.003). Both L1 and L2 were seen at marginally higher levels in
      tumour than normal tissues but the difference was not statistically significant.
      Levels of angiomotin were at significantly higher levels in grade 2 and grade 3
      tumours compared with grade 1 (p < 0.01 and p = 0.05 respectively). The levels of
      angiomotin in tumours from patients who had metastatic disease were also
      significantly higher than those patients who remained disease free (p = 0.03).
      Multivariate analysis indicated that angiomotin transcript was an independent
      prognostic factor (p = 0.031). No significant correlations were seen between
      angiomotin-L1 and L2 with the clinical outcome. Furthermore, high levels of
      angiomotin transcript were associated with shorter overall survival (p < 0.05).
      There was a high degree of correlation between levels of vW factor and that of
      angiomotin (p < 0.05), but not angiomotin-L1 and angiomotin-L2. CONCLUSION:
      Angiomotin, a putative endothelial motility factor, is highly expressed in human
      breast tumour tissues and linked to angiogenesis. It links to the aggressive
      nature of breast tumours and the long term survival of the patients. These data
      point angiomotin as being a potential therapeutic target.

PMID- 16430778
TI  - A domain-oriented approach to the reduction of combinatorial complexity in signal
      transduction networks.
AB  - BACKGROUND: Receptors and scaffold proteins possess a number of distinct domains
      and bind multiple partners. A common problem in modeling signaling systems arises
      from a combinatorial explosion of different states generated by feasible
      molecular species. The number of possible species grows exponentially with the
      number of different docking sites and can easily reach several millions. Models
      accounting for this combinatorial variety become impractical for many
      applications. RESULTS: Our results show that under realistic assumptions on
      domain interactions, the dynamics of signaling pathways can be exactly described
      by reduced, hierarchically structured models. The method presented here provides
      a rigorous way to model a large class of signaling networks using macro-states
      (macroscopic quantities such as the levels of occupancy of the binding domains)
      instead of micro-states (concentrations of individual species). The method is
      described using generic multidomain proteins and is applied to the molecule LAT.
      CONCLUSION: The presented method is a systematic and powerful tool to derive
      reduced model structures describing the dynamics of multiprotein complex
      formation accurately.

PMID- 16430780
TI  - Functional and phenotypical comparison of myofibroblasts derived from biopsies
      and bronchoalveolar lavage in mild asthma and scleroderma.
AB  - BACKGROUND: Activated fibroblasts, which have previously been obtained from
      bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the
      fibrotic processes of asthma and scleroderma (SSc). We have studied the motility
      for BALF derived fibroblasts in patients with SSc that may explain the presence
      of these cells in the airway lumen. Furthermore, we have compared phenotypic
      alterations in activated fibroblasts from BALF and bronchial biopsies from
      patients with mild asthma and SSc that may account for the distinct fibrotic
      responses. METHODS: Fibroblasts were cultured from BALF and bronchial biopsies
      from patients with mild asthma and SSc. The motility was studied using a cell
      migration assay. Western Blotting was used to study the expression of alpha
      smooth muscle actin (alpha-SMA), ED-A fibronectin, and serine arginine splicing
      factor 20 (SRp20). The protein expression pattern was analyzed to reveal
      potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing
      dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical
      significance. RESULTS: Increased migration and levels of ED-A fibronectin were
      observed in BALF fibroblasts from both groups of patients, supported by increased
      expression of RhoA, Rac1, and the splicing factor SRp20. However, these
      observations were exclusively accompanied by increased expression of alpha-SMA in
      patients with mild asthma. Compared to BALF fibroblasts in mild asthma,
      fibroblasts in SSc displayed a differential protein expression pattern of
      cytoskeletal- and scavenger proteins. These identified proteins facilitate cell
      migration, oxidative stress, and the excessive deposition of extracellular matrix
      observed in patients with SSc. CONCLUSION: This study demonstrates a possible
      origin for fibroblasts in the airway lumen in patients with SSc and important
      differences between fibroblast phenotypes in mild asthma and SSc. The findings
      may explain the distinct fibrotic processes and highlight the motile BALF
      fibroblast as a potential target cell in these disorders.

PMID- 16430781
TI  - Selective remodeling of cardiolipin fatty acids in the aged rat heart.
AB  - BACKGROUND: The heart is rich in cardiolipin, a phospholipid acylated in four
      sites, predominately with linoleic acid. Whether or not aging alters the
      composition of cardiolipin acyl chains is controversial. We therefore measured
      the fatty acid concentration of cardiolipin in hearts of 4, 12 and 24 month old
      rats that consumed one diet, adequate in fatty acids for the duration of their
      life. RESULTS: The concentration (nmol/g) of linoleic acid was decreased in 24
      month old rats (3965 +/- 617, mean +/- SD) vs 4 month old rats (5525 +/- 656),
      while the concentrations of arachidonic and docosahexaenoic acid were increased
      in 24 month old rats (79 +/- 9 vs 178 +/- 27 and 104 +/- 16 vs 307 +/- 68 for
      arachidonic and docosahexaenoic acids, 4 months vs 24 months, respectively).
      Similar changes were not observed in ethanolamine glycerophospholipids or plasma
      unesterified fatty acids, suggesting specificity of these effects to cardiolipin.
      CONCLUSION: These results demonstrate that cardiolipin remodeling occurs with
      aging, specifically an increase in highly unsaturated fatty acids.

PMID- 16430779
TI  - Mining literature for a comprehensive pathway analysis: a case study for
      retrieval of homocysteine related genes for genetic and epigenetic studies.
AB  - Homocysteine is an independent risk factor for cardiovascular diseases. It is
      also known to be associated with a variety of complex disorders. While there are
      a large number of independent studies implicating homocysteine in isolated
      pathways, the mechanism of homocysteine induced adverse effects are not clear.
      Homocysteine-induced modulation of gene expression through alteration of
      methylation status or by hitherto unknown mechanisms is predicted to lead to
      several pathological conditions either directly or indirectly. In the present
      manuscript, using literature mining approach, we have identified the genes that
      are modulated directly or indirectly by an elevated level of homocysteine. These
      genes were then placed in appropriate pathways in an attempt to understand the
      molecular basis of homocysteine induced complex disorders and to provide a
      resource for selection of genes for polymorphism screening and analysis of
      mutations as well as epigenetic modifications in relation to
      hyperhomocysteinemia. We have identified 135 genes in 1137 abstracts that either
      modulate the levels of homocysteine or are modulated by elevated levels of
      homocysteine. Mapping the genes to their respective pathways revealed that an
      elevated level of homocysteine leads to the atherosclerosis either by directly
      affecting lipid metabolism and transport or via oxidative stress and/or
      Endoplasmic Reticulum (ER) stress. Elevated levels of homocysteine also decreases
      the bioavailability of nitric oxide and modulates the levels of other metabolites
      including S-adenosyl methionine and S-adenosyl homocysteine which may result in
      cardiovascular or neurological disorders. The ER stress emerges as the common
      pathway that relates to apoptosis, atherosclerosis and neurological disorders and
      is modulated by levels of homocysteine. The comprehensive network collated has
      lead to the identification of genes that are modulated by homocysteine indicating
      that homocysteine exerts its effect not only through modulating the substrate
      levels for various catalytic processes but also through regulation of expression
      of genes involved in complex diseases.

PMID- 16430782
TI  - Pneumonia care and the nursing home: a qualitative descriptive study of resident
      and family member perspectives.
AB  - BACKGROUND: Nursing home residents are frequently sent to hospital for diagnostic
      tests or to receive acute health care services. These transfers are both costly
      and for some, associated with increased risks. Although improved technology
      allows long-term care facilities to deliver more complex health care on site, if
      this is to become a trend then residents and family members must see the value of
      such care. This qualitative study examined resident and family member
      perspectives on in situ care for pneumonia. METHODS: A qualitative descriptive
      study design was used. Participants were residents and family members of
      residents treated for pneumonia drawn from a larger randomized controlled trial
      of a clinical pathway to manage nursing home-acquired pneumonia on-site. A total
      of 14 in-depth interviews were conducted. Interview data were analyzed using the
      editing style, described by Miller and Crabtree, to identify key themes. RESULTS:
      Both residents and family members preferred that pneumonia be treated in the
      nursing home, where possible. They both felt that caring and attention are key
      aspects of care which are more easily accessible in the nursing home setting.
      However, residents felt that staff or doctors should make the decision whether to
      hospitalize them, whereas family members wanted to be consulted or involved in
      the decision-making process. CONCLUSION: These findings suggest that
      interventions to reduce hospitalization of nursing home residents with pneumonia
      are consistent with resident and family member preferences.

PMID- 16430784
TI  - Simultaneous detection of Fusarium culmorum and F. graminearum in plant material
      by duplex PCR with melting curve analysis.
AB  - BACKGROUND: Fusarium head blight (FHB) is a disease of cereal crops, which has a
      severe impact on wheat and barley production worldwide. Apart from reducing the
      yield and impairing grain quality, FHB leads to contamination of grain with toxic
      secondary metabolites (mycotoxins), which pose a health risk to humans and
      livestock. The Fusarium species primarily involved in FHB are F. graminearum and
      F. culmorum. A key prerequisite for a reduction in the incidence of FHB is an
      understanding of its epidemiology. RESULTS: We describe a duplex-PCR-based method
      for the simultaneous detection of F. culmorum and F. graminearum in plant
      material. Species-specific PCR products are identified by melting curve analysis
      performed in a real-time thermocycler in the presence of the fluorescent dye SYBR
      Green I. In contrast to multiplex real-time PCR assays, the method does not use
      doubly labeled hybridization probes. CONCLUSION: PCR with product differentiation
      by melting curve analysis offers a cost-effective means of qualitative analysis
      for the presence of F. culmorum and F. graminearum in plant material. This method
      is particularly suitable for epidemiological studies involving a large number of
      samples.

PMID- 16430783
TI  - Female asylum seekers with musculoskeletal pain: the importance of diagnosis and
      treatment of hypovitaminosis D.
AB  - BACKGROUND: Hypovitaminosis D is well known in different populations, but may be
      under diagnosed in certain populations. We aim to determine the first diagnosis
      considered, the duration and resolution of symptoms, and the predictors of
      response to treatment in female asylum seekers suffering from hypovitaminosis D.
      METHODS:  DESIGN: A pre- and post-intervention observational study. SETTING: A
      network comprising an academic primary care centre and nurse practitioners.
      PARTICIPANTS: Consecutive records of 33 female asylum seekers with complaints
      compatible with osteomalacia and with hypovitaminosis D (serum 25-(OH) vitamin D
      < 21 nmol/l). Treatment intervention: The patients received either two doses of
      300,000 IU intramuscular cholecalciferol as well as 800 IU of cholecalciferol
      with 1000 mg of calcium orally, or the oral treatment only. MAIN OUTCOME
      MEASURES: We recorded the first diagnosis made by the physicians before the
      correct diagnosis of hypovitaminosis D, the duration of symptoms before
      diagnosis, the responders and non-responders to treatment, the duration of
      symptoms after treatment, and the number of medical visits and analgesic drugs
      prescribed 6 months before and 6 months after diagnosis. TESTS: Two-sample t
      tests, chi-squared tests, and logistic regression analyses were performed.
      Analyses were performed using SPSS 10.0. RESULTS: Prior to the discovery of
      hypovitaminosis D, diagnoses related to somatisation were evoked in 30 patients
      (90.9%). The mean duration of symptoms before diagnosis was 2.53 years (SD 3.20).
      Twenty-two patients (66.7%) responded completely to treatment; the remaining
      patients were considered to be non-responders. After treatment was initiated, the
      responders' symptoms disappeared completely after 2.84 months. The mean number of
      emergency medical visits fell from 0.88 (SD 1.08) six months before diagnosis to
      0.39 (SD 0.83) after (P = 0.027). The mean number of analgesic drugs that were
      prescribed also decreased from 1.67 (SD 1.5) to 0.85 (SD 1) (P = 0.001).
      CONCLUSION: Hypovitaminosis D in female asylum seekers may remain undiagnosed,
      with a prolonged duration of chronic symptoms. The potential pitfall is a
      diagnosis of somatisation. Treatment leads to a rapid resolution of symptoms, a
      reduction in the use of medical services, and the prescription of analgesic drugs
      in this vulnerable population.

PMID- 16430785
TI  - In vitro and in vivo MMP gene expression localisation by In Situ-RT-PCR in cell
      culture and paraffin embedded human breast cancer cell line xenografts.
AB  - BACKGROUND: Members of the matrix metalloproteinase (MMP) family of proteases are
      required for the degradation of the basement membrane and extracellular matrix in
      both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type
      1-MMP) expression is higher in more invasive human breast cancer (HBC) cell
      lines, whilst in vivo its expression has been associated with the stroma
      surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated
      with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised
      around invasive cells of breast tumours in vivo. As MMPs are not stored
      intracellularly, the ability to localise their expression to their cells of
      origin is difficult. METHODS: We utilised the unique in situ-reverse
      transcription-polymerase chain reaction (IS-RT-PCR) methodology to localise the
      in vitro and in vivo gene expression of MT1-MMP, MMP-1 and MMP-3 in human breast
      cancer. In vitro, MMP induction was examined in the MDA-MB-231 and MCF-7 HBC cell
      lines following exposure to Concanavalin A (Con A). In vivo, we examined their
      expression in archival paraffin embedded xenografts derived from a range of HBC
      cell lines of varied invasive and metastatic potential. Mouse xenografts are
      heterogenous, containing neoplastic human parenchyma with mouse stroma and
      vasculature and provide a reproducible in vivo model system correlated to the
      human disease state. RESULTS: In vitro, exposure to Con A increased MT1-MMP gene
      expression in MDA-MB-231 cells and decreased MT1-MMP gene expression in MCF-7
      cells. MMP-1 and MMP-3 gene expression remained unchanged in both cell lines. In
      vivo, stromal cells recruited into each xenograft demonstrated differences in
      localised levels of MMP gene expression. Specifically, MDA-MB-231, MDA-MB-435 and
      Hs578T HBC cell lines are able to influence MMP gene expression in the
      surrounding stroma. CONCLUSION: We have demonstrated the applicability and
      sensitivity of IS-RT-PCR for the examination of MMP gene expression both in vitro
      and in vivo. Induction of MMP gene expression in both the epithelial tumour cells
      and surrounding stromal cells is associated with increased metastatic potential.
      Our data demonstrate the contribution of the stroma to epithelial MMP gene
      expression, and highlight the complexity of the role of MMPs in the stromal
      epithelial interactions within breast carcinoma.

PMID- 16430786
TI  - BACH1 Ser919Pro variant and breast cancer risk.
AB  - BACKGROUND: BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1
      interacting protein 1, BRIP1) is a helicase protein that interacts in vivo with
      BRCA1, the protein product of one of the major genes for hereditary
      predisposition to breast cancer. Previously, two BACH1 germ line missense
      mutations have been identified in early-onset breast cancer patients with and
      without family history of breast and ovarian cancer. In this study, we aimed to
      evaluate whether there are BACH1 genetic variants that contribute to breast
      cancer risk in Finland. METHODS: The BACH1 gene was screened for germ line
      alterations among probands from 43 Finnish BRCA1/2 negative breast cancer
      families. Recently, one of the observed common variants, Ser-allele of the
      Ser919Pro polymorphism, was suggested to associate with an increased breast
      cancer risk, and was here evaluated in an independent, large series of 888
      unselected breast cancer patients and in 736 healthy controls. RESULTS: Six BACH1
      germ line alterations were observed in the mutation analysis, but none of these
      were found to associate with the cancer phenotype. The Val193Ile variant that was
      seen in only one family was further screened in an independent series of 346
      familial breast cancer cases and 183 healthy controls, but no additional carriers
      were observed. Individuals with the BACH1 Ser919-allele were not found to have an
      increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70
      1.16; p = 0.427) or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76-1.35; p = 0.91)
      were compared to Pro/Pro homozygotes, and there was no association of the variant
      with any breast tumor characteristics, age at cancer diagnosis, family history of
      cancer, or survival. CONCLUSION: Our results suggest that the BACH1 Ser919 is not
      a breast cancer predisposition allele in the Finnish study population. Together
      with previous studies, our results also indicate that although some rare germ
      line variants in BACH1 may contribute to breast cancer development, the
      contribution of BACH1 germline alterations to familial breast cancer seems
      marginal.

PMID- 16430787
TI  - Virtual cooperativity in myoglobin oxygen saturation curve in skeletal muscle in
      vivo.
AB  - BACKGROUND: Myoglobin (Mb) is the simplest monomeric hemoprotein and its
      physicochemical properties including reversible oxygen (O2)binding in aqueous
      solution are well known. Unexpectedly, however, its physiological role in intact
      muscle has not yet been established in spite of the fact that the role of the
      more complex tetrameric hemoprotein, hemoglobin (Hb), in red cells is well
      established. Here, I report my new findings on an overlooked property of skeletal
      Mb. METHODS: I directly observed the oxygenation of Mb in perfused rat skeletal
      muscle under various states of tissue respiration. A computer-controlled rapid
      scanning spectrophotometer was used to measure the oxygenation of Mb in the
      transmission mode. The light beam was focused on the thigh (quadriceps) through a
      5-mm-diameter light guide. The transmitted light was conducted to the
      spectrophotometer through another 5-mm-diameter light guide. Visible difference
      spectra in the range of 500-650 nm were recorded when O2 uptake in the hindlimb
      muscle reached a constant value after every stepwise change in the O2
      concentration of the buffer. RESULTS: The O2 dissociation curve (ODC) of Mb, when
      the effluent buffer O2 pressure was used as the abscissa, was of a sigmoid shape
      under normal and increased respiratory conditions whereas it was of rectangular
      hyperbolic shape under a suppressed respiratory condition. The dissociation curve
      was shifted toward the right and became more sigmoid with an increase in tissue
      respiration activity. These observations indicate that an increase in O2 demand
      in tissues makes the O2 saturation of Mb more sensitive to O2 pressure change in
      the capillaries and enhances the Mb-mediated O2 transfer from Hb to cytochrome
      oxidase (Cyt. aa3), especially under heavy O2 demands. CONCLUSION: The virtual
      cooperativity and O2 demand-dependent shifts of the ODC may provide a basis for
      explaining why Mb has been preserved as monomer during molecular evolution.

PMID- 16430788
TI  - Orbital decompression surgery for thyroid eye disease: implications for
      anaesthesia.
AB  - The management of thyroid-associated eye disease is reviewed with particular
      reference to surgical management and its implications for anaesthetists.
      Experience from a unit undertaking such surgery is presented.

PMID- 16430789
TI  - High-affinity blockade of voltage-operated skeletal muscle sodium channels by 2,6
      dimethyl-4-chlorophenol.
AB  - BACKGROUND AND OBJECTIVE: The aromatic alcohol most closely resembling the
      aromatic tail of lidocaine is 2,6-dimethylphenol. This agent is as potent as
      lidocaine in blocking voltage-operated sodium channels. The aim of this study was
      to show the effect of halogenation in the para-position on the potency of this
      compound to block voltage-operated sodium channels. METHODS: Insertion of the
      halogen chloride into the para-position of the molecule 2,6-dimethylphenol
      yielded 2,6-dimethyl-4-chlorophenol. Block of sodium currents by this compound
      was studied using heterologously expressed voltage-operated rat neuronal (rat
      IIa) sodium channels. RESULTS: 2,6-dimethyl-4-chlorophenol reversibly suppressed
      depolarization-induced whole-cell sodium inward currents. The ECR50 for block of
      resting channels at a hyperpolarized holding potential (-150 mV) was 127
      micromol, the Hill coefficient nH 1.7. Membrane depolarization inducing either
      fast or slow-inactivation strongly increased the blocking potency. This is an
      important feature of a local-anaesthetic-like action. The estimated half-maximum
      effect concentration for the fast-inactivated channel state ECI50 was 28
      micromol, the Hill coefficient nH 3.8. When 20-30% of channels were slow
      inactivated using long (2.5 s) prepulses, followed by a 10 ms repolarization
      period to allow recovery from fast inactivation, the IC50 at -100 mV holding
      potential was reduced to 53 micromol. CONCLUSION: These results, which show that
      2,6-dimethyl-4-chlorophenol blocks voltage-operated sodium channels in a
      lidocaine-like manner while having a several fold higher potency than the non
      halogenated parent compound, highlight a potentially meaningful principle of
      increasing the sodium channel blocking potency of phenol derivatives.

PMID- 16430790
TI  - Inhibition of neuronal nitric oxide synthase reduces the propofol requirements in
      wild-type and nNOS knockout mice.
AB  - BACKGROUND AND OBJECTIVE: The glutamate-nitric oxide-cyclic guanosine
      monophosphate pathway has been identified as a potential target for anaesthetic
      agents. However, mice deficient in neuronal nitric oxide synthase have a similar
      susceptibility to volatile anaesthetic agents to wild-type mice and are not
      affected by non-isoform selective inhibitors. We hypothesized that the neuronal
      nitric oxide synthase selective inhibitor, 7-nitroindazole, would also reduce the
      propofol requirements in wild-type mice but would have no effect in neuronal
      nitric oxide synthase knockout mice. METHODS: We determined the time to loss of
      righting reflex, time to painful stimulus and time to regaining the righting
      reflex in neuronal nitric oxide synthase knockout and wild-type mice following
      the intraperitoneal injection of propofol in untreated, 7-nitroindazole and
      vehicle only treated animals (n = 6 per group). Propofol (200 mg kg(-1)) resulted
      in loss of righting reflex in the untreated and vehicle only groups but was
      lethal in 7-nitroindazole pre-treated mice, requiring a reduced dose of propofol
      (100 mg kg(-1)). RESULTS: 7-nitroindazole pre-treatment significantly reduced the
      loss of righting reflex (P < 0.001) in both wild-type and knockout mice when
      compared to untreated and vehicle only pre-treated animals, but had no effect on
      time to painful stimulus or regaining of the righting reflex. 7-nitroindazole
      reduced the propofol requirements in knockout mice to the same extent as in wild
      type animals. CONCLUSIONS: Propofol exerts its anaesthetic effects at least
      partially via the glutamate-nitric oxide-cyclic guanosine monophosphate pathway.
      The neuronal nitric oxide synthase knockout mice are sensitive to neuronal nitric
      oxide synthase selective inhibition suggesting that compensatory pathways in
      neuronal nitric oxide synthase knockout mice exist.

PMID- 16430791
TI  - Bispectral index-controlled anaesthesia for electroconvulsive therapy.
AB  - BACKGROUND: The suggested induction dose of methohexital for electroconvulsive
      therapy (ECT) varies widely influencing efficacy of ECT and safety of
      anaesthesia. Bispectral index (BIS), a monitor of consciousness, may be useful to
      assure adequate hypnosis with optimized methohexital dose. METHODS: Patients with
      medically resistant major depression (ICD10), scheduled for multiple ECT's, were
      studied. Depth of anaesthesia was BIS controlled. ECT was not performed until BIS
      dropped below 50. Initially anaesthesia was induced with methohexital 1.0 mg kg(
      1), and stepwise reduced by 0.1 mg kg(-1) during consecutive treatments. If BIS
      did not drop below 50, the methohexital was supplemented by further boluses of
      0.5 mg kg(-1), until the desired level of hypnosis was reached. The adequacy of
      the anaesthetic recommendation for methohexital (1.0-1.5 mg kg(-1)) as well as
      the psychiatric recommendation (0.75-1 mg kg(-1)) was investigated. RESULTS: One
      hundred and nine ECT's in 14 patients were studied. The recommended anaesthetic
      dose (1.0-1.5 mg kg(-1)) was inadequate in 40% of the treatments, with 12%
      exceeding 1.5 mg kg(-1), and 28% below 1.0 mg kg(-1). Psychiatric recommendation
      (0.75-1.0 mg kg(-1)) was inadequate in 49%, with 39% exceeding 1.0 mg kg(-1) and
      10% undershooting at 0.75 mg kg(-1). CONCLUSIONS: Methohexital for ECT showed a
      great variability, exceeding as well as undershooting the dosage recommendations
      widely. BIS monitoring may be useful to secure adequate hypnosis during muscle
      relaxation and treatment and may optimize ECT efficacy.

PMID- 16430792
TI  - Cerebral state monitor, a new small handheld EEG monitor for determining depth of
      anaesthesia: a clinical comparison with the bispectral index during day-surgery.
AB  - BACKGROUND AND OBJECTIVE: The cerebral state index (CSI) derived from a new small
      handheld electroencephalogram monitor was studied during routine day surgical
      anaesthesia titrated according to the bispectral index (BIS). The objective was
      to determine the degree of agreement between the two monitors. METHODS:
      Anaesthesia was induced with propofol and fentanyl (0.1 mg) in 38 patients
      undergoing general anaesthesia for routine day-surgery. Maintenance anaesthesia
      (sevoflurane (20/38), desflurane (10/38) or propofol (8/38)) titrated by BIS XP
      (Aspect Medical, Natwick, MA, USA) and BIS and CSI (cerebral State Monitor,
      Danmeter; Odense, Denmark) index values were recorded every minute. No patient
      received muscle relaxation. Observer's Assessment of Alertness/Sedation rating
      scale was used to assess level of sedation. RESULTS: Pair-wise recordings (914)
      of CSI and BIS were collected. The indices showed similar pattern and decreased
      with increasing level of sedation, however with large ranges for each level of
      sedation. Median indices were similar during surgery (BIS: 50 (14-89); CSI: 51 (7
      88)) and both indices increased (P 20% from BIS-index in 24% of readings, and on
      rare occasions CSI indices deviated >100% from the BIS reading. When BIS < 40,
      CSI decreased slower than BIS and with wider spreading. CONCLUSIONS: When used
      for day-surgery anaesthesia without muscle relaxation, CSI and BIS show similar
      patterns and numerical values but with the incidence of occasionally large
      discrepancies between pair-wise readings. Which monitor is the more dependable
      remains to be established and cannot be implied from this initial explorative
      study.

PMID- 16430793
TI  - Antipruritic and antiemetic effect of epidural droperidol: comparative study
      between single and continuous epidural injection.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to investigate whether single
      epidural droperidol or continuous epidural droperidol inhibit pruritus and
      postoperative nausea and vomiting induced by postoperative continuous epidural
      fentanyl administration, and to identify the optimal method of administering
      epidural droperidol. METHODS: 120 ASA I-II patients undergoing subtotal
      gastrectomy with general anaesthesia combined with epidural anaesthesia were
      randomly allocated into three groups: control (no droperidol), single injection
      (droperidol 2.5 mg) and continuous group (droperidol 2.5 mg 2 day(-1)).
      Postoperatively the frequency and severity of pruritus and postoperative nausea
      and vomiting in all groups were compared during 48 h. RESULTS: The frequency and
      severity of pruritus was significantly lower in both single injection and
      continuous groups than control group after epidural fentanyl administration (P <
      0.05). The frequency and severity of postoperative nausea and vomiting was
      significantly lower in single injection group than control group after epidural
      fentanyl administration (P < 0.05). CONCLUSION: Epidural continuous droperidol is
      effective for reducing pruritus, and single epidural droperidol injection is
      effective for reducing pruritus and postoperative nausea and vomiting induced by
      postoperative continuous epidural fentanyl analgesia.

PMID- 16430794
TI  - Does perioperative administration of rofecoxib improve analgesia after spine,
      breast and orthopaedic surgery?
AB  - BACKGROUND AND OBJECTIVE: Data on the effectiveness of cyclooxygenase 2
      inhibitors in postoperative pain therapy vary widely. We tested in a prospective,
      placebo-controlled, randomized, double-blind trial the hypotheses that
      perioperative (i.e. preoperative and postoperative) administration of the
      cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine
      consumption after spine, breast and orthopaedic surgery. METHODS: Five hundred
      and forty patients scheduled for spine, breast or orthopaedic surgery were
      randomly assigned to receive in combination with postoperative morphine via
      patient controlled analgesia pump for 4 days either rofecoxib 50 mg administered
      perioperatively, rofecoxib 50 mg administered only postoperatively, or placebo.
      Primary outcome criteria were pain score at rest (numeric rating scale 0-4) and
      morphine consumption. RESULTS: Perioperative rofecoxib significantly decreased
      pain score 0 (0-1) vs. 1 (0-2) (median (interquartile range)), and morphine
      consumption 18 (6-33) vs. 22.5 (12-38) compared with placebo. In contrast,
      rofecoxib when administered only postoperatively did not significantly improve
      analgesic effects or side-effects at time of assessment of the main criteria (24
      h after skin closure), but during the follow-up period at 48 h and 72 h after
      skin closure pain scores and morphine consumption were improved compared to
      placebo. The analgesic effects of rofecoxib were independent from the type of
      surgery. CONCLUSIONS: Perioperative administration of the cyclooxygenase 2
      inhibitor rofecoxib decreases pain scores and morphine consumption after
      orthopaedic, breast and spine surgery. However, the benefit of preoperative
      administration of the cyclooxygenase 2 inhibitor seems to be only moderate,
      suggesting that early postoperative administration may be a useful alternative
      approach. There is no evidence that the type of surgery influences analgesic
      effects of cyclooxygenase 2 inhibitors.

PMID- 16430795
TI  - Comparison of the laryngeal mask (LMA) and laryngeal tube (LT) with the new
      perilaryngeal airway (CobraPLA) in short surgical procedures.
AB  - BACKGROUND AND OBJECTIVE: We compared the laryngeal mask airway (LMA) and the
      laryngeal tube (LT) with the newly introduced perilaryngeal airway (CobraPLA,
      PLA) with regard to haemodynamic responses induced by airway insertion, clinical
      performance and occurrence of postoperative sore throat after short surgical
      procedures. METHODS: After premedication, 90 ASA I-II patients awaiting short
      surgical procedures were randomized to receive, LMA, LT or PLA. Anaesthesia was
      induced with intravenous propofol (2.5 mg kg(-1)) and mivacurium (0.2 mg kg(-1)).
      Number of attempts, time of insertion of the device, any other unwanted effect,
      mean aterial pressure, heart rate, oxygen saturation and end-tidal carbon dioxide
      were recorded. At the end of surgery, the cuff of the device was immediately
      deflated and the airway device was removed. The device was examined and noted for
      the presence of visible blood. Patients were asked to rate their throat soreness,
      dysphonia and dysphagia 1 and 24 h postoperatively. RESULTS: There were no
      differences in haemodynamic variables. Insertion times for the devices were
      similar (LMA: 20 +/- 11 s, LT: 19 +/- 14 s and PLA: 21 +/- 12 s.) The success
      rates at first insertion were lower in the (LMA group (57%) when compared with
      the PLA (97%, P < 0.05). The number and type of airway interventions for
      achieving an effective airway were similar. When the airways were removed 50% of
      the PLA devices had positive blood traces, while only 17% of the LMA and LT
      devices had positive blood traces (P < 0.01). Fifty percent of the patients
      suffered from a sore throat in the PLA group, which was significantly higher than
      in the LMA and LT groups (P < 0.05). CONCLUSION: We conclude that haemodynamic,
      ventilation and oxygenation variables throughout the surgery were similar with,
      LMA, LT and PLA, but LT and PLA were easier to insert; LMA and LT caused less
      mucosal trauma.

PMID- 16430796
TI  - A novel point-of-care information system reduces anaesthesiologists' errors while
      managing case scenarios.
AB  - BACKGROUND AND OBJECTIVES: The On-Line Electronic Help (OLEH) is a point-of-care
      information system for anaesthesia providers prepared by the European Society of
      Anaesthesiologists. In this preliminary study the effect of the OLEH availability
      on the incidence of knowledge-based errors during the management of case
      scenarios and participants' subjective evaluation of the OLEH were evaluated.
      METHODS: After a short training session, 48 anaesthesiologists (24 junior
      residents, 12 senior residents and 12 board-certified) were presented randomly
      with six computer screen-based case scenarios with, and six without, the option
      of using the OLEH. Two reviewers evaluated the answers independently according to
      preconfigured guidelines. RESULTS: The availability of the OLEH was associated
      with higher scores in 11 of the 12 scenarios, and with a decrease in the
      incidence of critical errors in 10 scenarios. Time to task completion was
      increased in one scenario only when the OLEH was used. The degree of professional
      experience was associated with better scores in five of the scenarios and with a
      reduced occurrence of critical errors in three scenarios. Forty-two out of 48
      participants stated that finding information in the OLEH software was easy and
      that the system was helpful in managing the scenarios. CONCLUSIONS: This
      preliminary study demonstrates the potential value of the OLEH in decreasing the
      number of knowledge-based errors made by anaesthesiologists. According to the
      encouraging results, the OLEH system is currently under evaluation using full
      scale simulation scenarios in an operating room environment.

PMID- 16430797
TI  - Post-duty psychomotor performance in young and senior anaesthetists.
AB  - BACKGROUND AND OBJECTIVE: The level of performance in junior and senior
      anaesthetists was investigated after 24-h shift working and on-call duties.
      METHODS: Pre- and post-duty psychomotor function, influence on response time,
      cognitive function and well-being in 23 individuals (13 junior and 12 senior
      anaesthetists) was assessed before and after 24-h in-house on-call duty.
      Subjective perception of tiredness and concentration abilities was estimated by
      applying a visual analogue scale. RESULTS: The self-assessed tiredness prior to
      duty was high in both age groups and significantly increased in senior
      anaesthetists after night duty (P = 0.01). Post-duty impairment of concentration
      abilities was reported in both groups. Comparing results from pre- and post-duty
      psychometric testing showed a comparable decline in junior and senior
      anaesthetists as well. Assessment of burnout showed a significant lack of
      personal accomplishment in junior anaesthetists as compared to their older
      colleagues (P = 0.038). Senior anaesthetists judged their contribution to patient
      well-being significantly higher than did their younger colleagues (P = 0.035).
      CONCLUSIONS: Although tiredness and subjective impairment of concentration
      abilities was high in senior anaesthetists after 24-h in-house on-call duty,
      performance assessed by psychometric testing does not support the hypothesis that
      senior colleague's performance cannot keep up with routine hospital shift work.

PMID- 16430798
TI  - Modified nasal cannula for simultaneous oxygen delivery and end-tidal CO2
      monitoring during spontaneous breathing.
AB  - BACKGROUND AND OBJECTIVES: Supplemental oxygen is commonly given via nasal
      cannulae in spontaneously breathing patients. Our modified nasal cannula with a
      clamp between the nasal prongs can provide O2 via one nostril and CO2 can be
      sampled through the other one. We have studied whether this cannula can provide
      oxygenation similar to a standard cannula without affecting end-tidal CO2
      monitoring. METHODS: Eighty-six patients were studied during spinal anaesthesia
      and sedation. In 15 patients, arterial blood was sampled while O2 was delivered
      at flow rates of 0, 2 and 4 L min(-1), with or without clamping between the
      prongs of our modified nasal cannula. In the remaining 71 patients, arterial O2
      was measured while using our modified nasal cannula with the clamp applied. End
      tidal CO2 was recorded on a capnograph and the correlation between end-tidal and
      arterial values with our modified nasal cannula was investigated. RESULTS: No end
      tidal CO2 waveforms were found with oxygen flow greater than 2L min(-1) without
      clamping between the prongs. With clamping there was a significant correlation (r
      = 0.83) between arterial and end-tidal CO2. A Bland-Altman analysis revealed a
      bias of 0.49 kPa with precision of +/-0.76 kPa. Arterial oxygenation was not
      affected by our modified nasal prongs with clamp as compared to the standard
      cannula. CONCLUSION: Our modified nasal cannula can provide continuous monitoring
      of end-tidal CO2 without affecting oxygen delivery in sedated, spontaneously
      breathing patients.

PMID- 16430799
TI  - Aprotinin and renal function at cardiac surgery.

PMID- 16430800
TI  - Brachial plexus injury during anaesthesia in patients receiving cisplatin-based
      chemotherapy.

PMID- 16430802
TI  - Anaesthesia for total hip replacement in Gaucher's disease.

PMID- 16430803
TI  - Cerebral oximetry monitoring during unexpected cardiopulmonary arrest and tension
      pneumothorax.

PMID- 16430806
TI  - [Acute heart failure--on its way toward evidence-based treatment].

PMID- 16430807
TI  - [Levosimendan--an alternative to conventional inotropic treatment of patients
      with acute heart failure?].
AB  - In acute heart failure the myocardial function is acutely reduced and the
      oxygenation of the tissues becomes inadequate. Traditional inotropic drugs
      improve the haemodynamics and give symptomatic relief, but the evidence of
      injurious effects on morbidity and mortality restricts their use. The need for
      new inotropic drugs which can also reduce morbidity and mortality is for that
      reason obvious. Levosimendan is such a new drug in a new class (Ca2+ sensitizers)
      of positive inotropic drugs with favourable effects compared to existing
      treatment possibilities.

PMID- 16430808
TI  - [The three types of influenza].
AB  - The unprecedented spread of the highly pathogenic avian influenza type A H5N1 is
      a threat to veterinary public health. However, the virus does not in its present
      form constitute a major threat to human public health. Only if the virus mutates
      to spread effectively from person to person will there be a risk of a new
      pandemic. It is not possible to predict if this will happen, when it may happen
      or how serious it may be. At present, seasonal influenza represents the greatest
      burden of illness among the three types of influenza A illness: seasonal, avian,
      and pandemic influenza.

PMID- 16430809
TI  - [Diabetic ketoacedosis].
AB  - The diagnosis of diabetic ketoacedosis (DKA) may be based upon simple biochemical
      findings. Measurement of b-hydroxybutyrate in blood may replace semi-quantitative
      measurement of acetoacetic acid in urine. A list of criteria of graduating
      severity is suggested for the selection of patients to be treated in intensive
      care units. During treatment, intensive rehydration with sodium chloride for a
      longer period may induce metabolic acidosis. Terminating a regimen of intravenous
      insulin infusion requires knowledge of the difference in the duration of action
      of intravenous versus subcutaneous insulin.

PMID- 16430810
TI  - [Endoscopic retrograde cholangiopancreatography in patients with acute gallstone
      associated pancreatitis].

PMID- 16430811
TI  - [Electrocardiography. Tips & tricks].

PMID- 16430812
TI  - [Length of stay after primary total hip and knee arthroplasty in Denmark, 2001
      2003].
AB  - INTRODUCTION: We studied length of stay (LOS) after operation with total hip
      arthroplasty (THA) and total knee arthroplasty (TKA) in Denmark from 2001 to 2003
      to determine whether experiences from published accelerated tracks had been
      implemented in Denmark, resulting in reduced LOS. MATERIALS AND METHODS: Through
      the National Patient Registry (Landspatientregistret) we obtained information on
      numbers, sex, age and LOS for each year during the period 2001-2003, inclusive.
      RESULTS: In 2003 the male-female sex ratios for THA and TKA were 1:1.4 and 1:1.7,
      respectively. In 2003, the mean age at operation with THA was 66.0 years for men
      and 69.9 years for women; 66.9 years for men and 69.0 years for women operated on
      with TKA. During the period studied, LOS was reduced for both operations: 16% for
      THA, to a mean of 8.1 days, and 17% for TKA, to a mean of 8.6 days, in 2003. LOS
      increased with age for both THA and TKA. Men had shorter LOS than women.
      DISCUSSION: The LOS shows that accelerated tracks - with accompanying shorter LOS
      in the area of 4 to 6 days - have not been implemented on a nationwide basis, and
      we find a need to review the principles for rehabilitation after operation with
      THA and TKA in the direction of accelerated tracks. This could be expected not
      only to generate large savings in LOS but also to reduce the need for
      rehabilitation and possibly reduce morbidity.

PMID- 16430813
TI  - [Patients' attitude towards the hospital system in eastern and western Denmark.
      Patient involvement, patient orthodoxy and information gathering].
AB  - INTRODUCTION: Based on results from the Danish National Patient Satisfaction
      Survey (2000, 2002), which showed that patients treated in hospitals in western
      Denmark (West) had more positive experiences than patients treated in hospitals
      in eastern Denmark (East), the Unit of Patient Evaluation examined what factors
      may be creating the regional differences in patients' experiences. MATERIALS AND
      METHODS: This research is based on qualitative research methods and has decoded
      the sense ascribed by each patient, based on his or her own understanding, norms
      and values, to phenomena and experiences during hospitalisation. The research was
      carried out in four orthopaedic departments, and hip patients were chosen as the
      target group. In all, 16 interviews with patients, 9 interviews with medical
      personnel and 4 observations were carried out. RESULTS: All the patients
      preferred to be informed about their treatment possibilities. Nevertheless,
      compared to patients in the West, patients in the East had more specific
      expectations of being involved in their hospitalisation, they had more often
      tried to get involved and they were less orthodox and more engaged in obtaining
      information. DISCUSSION: This research indicates that the difference in patients'
      experiences between eastern and western Denmark may be caused by their different
      expectations of involvement. An individual patient's evaluation of
      hospitalisation may be more positive if the patient does not have a high
      expectation of having his or her individual needs fulfilled.

PMID- 16430814
TI  - [Intrafamily kidney transplantation. Investigation of its influence on the
      donor's life and his or her relationship with the recipient].
AB  - INTRODUCTION: Quality of life is a vital aspect to be considered in connection
      with intrafamily kidney transplantations. It is important that the donor be both
      physically and mentally well after the donation. It is also crucial that the
      relationship between the donor and recipient not change for the worse. MATERIALS
      AND METHODS: 45 of 78 donors entered into our investigation. All had donated a
      kidney to a family member at Odense University Hospital between 1 January 1995
      and 7 January 2003. All were interviewed using a semi-structured questionnaire
      covering both physical, social and mental issues and the donor's relationship
      with the recipient. RESULTS: The vast majority were satisfied with their decision
      to donate. Their relationship with the recipient was either the same or had
      improved. The donors had not felt pressured to donate. 25% still had some
      discomfort/pain, which was mainly from the scar; 47% had not changed mentally;
      38% had changed mentally in a positive direction; 91% had not changed socially,
      but 9% had changed in a negative way. Physically, 82% felt the same as before the
      donation; 16% were less active physically. DISCUSSION: Intrafamily kidney
      transplantation is a good way to help kidney patients. Within the limits of the
      survey, the risk of suffering a lower quality of life after donating was shown to
      be low. The discomfort/pain was of limited inconvenience. On the contrary, the
      investigation showed that most often the donor was getting better mentally and
      his or her relationship with the recipient had changed for the better. However,
      there is room for improvement in operative techniques and donor selection.

PMID- 16430815
TI  - [Picture of the month: cutaneous manifestations of vitamin C deficiency].

PMID- 16430816
TI  - [Ventricular fibrillation caused by a misplaced Sengstaken tube].
AB  - Uncontrollable hemorrhage from esophageal varicose veins in portal hypertension
      and cirrhosis of the liver may be treated with a Sengstaken-Blakemore tube. A
      case of ventricular fibrillation caused by a misplaced Sengstaken-Blakemore tube
      is described. Patients with a Sengstaken-Blakemore tube in place should be
      checked by a trained nurse for early signs of misplacement of the tube.

PMID- 16430817
TI  - [Pediatric septic shock--timing, volume resuscitation and anticoagulation
      therapy].
AB  - Pediatric septic shock is associated with severe hypovolemia, and children
      frequently respond well to aggressive volume resuscitation. In recent years,
      improved outcome has been reported when aggressive volume resuscitation and goal
      directed therapies were applied to children with septic shock. We report a case
      of severe meningococcal septic shock in a child aged 16 months where aggressive
      volume resuscitation and anticoagulation therapy were applied.

PMID- 16430818
TI  - [Primary eosinophilic esophagitis].
AB  - Primary eosinophilic esophagitis (EE) is a rare disease with symptoms similar to
      those of gastroesophageal reflux disease (GERD). However, EE is caused by severe
      eosinophilic invasion of the esophageal epithelium, typically followed by
      dysphagia. A man 28 years of age presented persistent symptoms of GERD despite
      traditional antireflux therapy. Histologic evaluation showed eosinophilia (85
      eosinophils/high-power field (x 400)). Treatment by bouginage resulted in mucosal
      lacerations and transitory clinical improvement. Local steroid therapy for four
      weeks eliminated the symptoms.

PMID- 16430819
TI  - [Should early abortion be treated medically?].

PMID- 16430828
TI  - [Erroneous use of the "EuroQol" indication for quality measurement in
      Ugeskriftet].

PMID- 16430829
TI  - [Use of thoracic CT in staging of colorectal cancer].

PMID- 16430831
TI  - [The good and the evil recovery].

PMID- 16430835
TI  - [Medical Museion: our cultural heritage is endangered!].

PMID- 16430844
TI  - Using data linkage to generate 30-day crash-fatality adjustment factors for
      Taiwan.
AB  - Different countries have their own police reporting time standards for counting
      the number of fatalities in reported crashes. A rapid estimation method (such as
      adjustment factor) for the comparison is important. The data-linkage technique
      was used to combine police-reported crash data and vital registration data, in
      order to generate 30-day fatality adjustment factors for various reporting time
      standards, which could also shed light on the fatal injury trend over time. The
      major findings were as follows. Firstly, a conservative 30-day fatality
      adjustment factor for the first day (or 24 h) would be 1.54 (or 1.35) in an area
      with a large motorcycle population, like Taiwan. This produced 20-40% higher 30
      day fatalities than UK Transport Research Laboratory predicted, and 15-25% higher
      fatalities than those in Europe/Japan. Secondly, after excluding motorcycle
      impacts, the Taiwanese factors suggested 8-14% higher fatalities within 30 days
      than those in Europe/Japan. Third, motorcycle fatalities influenced the overall
      30-day fatality trend within 3 days. In the future, both the police under
      reporting problem and the motorcycle/overall fatal injury pattern within 3 days
      after crashing in developing countries like Taiwan merit further investigation.

PMID- 16430845
TI  - The relationship between safety climate and injury rates across industries: the
      need to adjust for injury hazards.
AB  - Previous studies have suggested that strong safety climates (shared perceptions
      of safe conducts at work) are associated with lower workplace-injury rates, but
      they rarely control for differences in industry hazards. Based on 33 companies,
      we assessed its association with injury rates using three rate based injury
      measures (claims per 100 employees, claims per 100,000 h worked, and claims per 1
      million US dollars payroll), which were derived from workers' compensation injury
      claims. Linear regression models were used to test the predictability of safety
      climate on injury rates, followed by controlling for differences in hazard across
      industries gauged by national industry-specific injury rates. In the unadjusted
      model, company level safety climate were negatively and significantly associated
      with injury rates. However, all of the above associations were no longer apparent
      when controlling for the hazardousness of the specific industry. These findings
      may be due to over adjustment of hazard risk, or the overwhelming effects of
      industry specific hazards relative to safety climate effects that could not be
      differentiated with the statistical power in our study. Industry differences in
      hazard, conceptualized as one type of injury risk, however need to be considered
      when testing the association between safety climate and injury across different
      industries.

PMID- 16430846
TI  - Normalization of metabolites in heterogenous systems using genomics.

PMID- 16430847
TI  - Reactions of *NO2 with chromium(III) complexes with histamine and pyridoxamine
      ligands studied by the stopped-flow technique.
AB  - This study demonstrated the direct formation of the nitrogen dioxide (*NO2)
      radical during the decomposition of 3-morpholinosydnonimine (SIN-1) in biological
      buffer 4-morpholinoethanosulfone acid solution. Consequently, at approximately pH
      4, SIN-1 can be used successfully as a source of *NO2. This conclusion is drawn
      from a comparison of the reactions of cis-[Cr(C2O4)(L- L)(OH2)2]+, where L-L
      denotes pyridoxamine (Hpm) or histamine (hm), with the gaseous *NO2 radical
      obtained by two methods: from SIN-1 and from a simple redox reaction. These
      reactions were investigated using the stopped-flow technique. The measurements
      were carried out at temperatures ranging from 5 to 25 degrees C over a pH range
      from 6.52 to 9.11 for cis-[Cr(C2O4)(Hpm) (OH2)2]+ and from 6.03 to 8.15 for cis
      [Cr(C2O4)(hm)(OH2)2] +. We also determined the thermodynamic activation parameter
      (E(a)) and the uptake mechanism for each of the coordination compounds studied.

PMID- 16430848
TI  - Selective inhibition of matrix metalloproteinase 2 (gelatinase A) by barium
      chloride.

PMID- 16430849
TI  - Correlating the fractional inhibition of caspase-3 in NT2 cells with apoptotic
      markers using an active-caspase-3 enzyme-linked immunosorbent assay.
AB  - A rapid and quantitative method for measuring the activity and fractional
      inhibition of enzymes within their natural cellular environment remains an unmet
      need in drug discovery. We describe the use of a nonradioactive quantitative
      enzyme-linked immunosorbent assay (ELISA) for measuring intracellular caspase
      activity that is amenable to robotic automation. The ELISA specifically detects
      active-caspase-3 and was used to correlate the in-cell activity of caspase-3 with
      the progress of caspase-3-mediated events under varying concentrations of caspase
      3 inhibitors in NT2 cells. We examined the cleavage of endogenous substrates
      (poly(ADP-ribose)polymerase and alphaII-spectrin), the extent of DNA
      fragmentation, and the autocatalytic removal of the caspase-3 prodomain as
      markers of caspase-3 activity. To impart inhibition of the downstream markers, a
      greater level of caspase-3 inhibition was required. Although the functional
      markers were found not to accurately predict intracellular caspase-3 activity, we
      found that the inhibition of intracellular caspase-3 was highly correlated (R(2)
      = 0.96) to the inhibition of DNA fragmentation. Also, by comparing the potency of
      the different inhibitors against the intracellular enzyme versus the purified
      enzyme, the effects of inhibitor functional groups on whole-cell activity were
      addressed.

PMID- 16430850
TI  - Interfacing myoglobin to graphite electrode with an electrodeposited nanoporous
      ZnO film.
AB  - A biocompatible, nanoporous ZnO film was prepared on graphite electrode by the
      simple electrodeposition method. Based on the film's strong adsorption ability
      and friendly microenvironment, it can be used as a good matrix to immobilize
      myoglobin (Mb) through simple adsorption. Moreover, the entrapped Mb realized
      direct electron transfer with the electrode and displayed an elegant catalytic
      activity toward the reduction of hydrogen peroxide, nitrite, and trichloroacetic
      acid, by which the mediator-free biosensors could be fabricated. Atomic force
      microscopy, UV-Vis spectra, electrochemical impedance spectroscopy, and cyclic
      voltammetry, etc. were used to characterize the nanoporous ZnO film and Mb
      modified ZnO film. Compared to other methods, electrodeposition of porous
      material supplied a more simple and convenient approach to prepare biocompatible
      materials for biosensors.

PMID- 16430852
TI  - Spectrophotometric assay for quantitative determination of 7-aminocephalosporanic
      acid from direct hydrolysis of cephalosporin C.

PMID- 16430851
TI  - Enhancing the efficiency of cell-free protein synthesis through the polymerase
      chain-reaction-based addition of a translation enhancer sequence and the in situ
      removal of the extra amino acid residues.
AB  - A method for the rapid generation of intact proteins in a cell-free protein
      synthesis system was developed. The productivity of the recombinant proteins from
      the polymerase-chain-reaction-amplified templates was enhanced remarkably using
      an optimized translation enhancer sequence. The extra amino acid residues derived
      from the translation enhancer sequence were effectively removed by utilizing the
      appropriate detergent and peptide cleavage enzyme in the reaction mixture. These
      results demonstrate the versatility of cell-free protein synthesis in providing
      optimized and customized reaction conditions for the efficient production of the
      desired proteins.

PMID- 16430853
TI  - Multilayer membranes for glucose biosensing via layer-by-layer assembly of
      multiwall carbon nanotubes and glucose oxidase.
AB  - A bilayer of the polyelectrolytes poly(dimethyldiallylammonium chloride) (PDDA)
      and poly(sodium 4-styrenesulfonate) (PSS) was formed on a 3-mercapto-1
      propanesulfonic-acid-modified Au electrode. Subsequently, multiwall carbon
      nanotubes (MWCNTs) wrapped by positively charged PDDA were assembled layer-by
      layer with negatively charged glucose oxidase (GOx) onto the PSS-terminated
      bilayer. Electrochemical impedance spectroscopy and atomic force microscopy were
      adopted to monitor the regular growth of the PDDA-MWCNTs/GOx bilayers. Using GOx
      as a model enzyme, the assembled multilayer membranes showed some striking
      features such as the adsorbed form of GOx on individual MWCNT, uniformity, good
      stability, and electrocatalytic activity toward oxygen reduction. Based on the
      consumption of dissolved oxygen during the oxidation process of glucose catalyzed
      by the immobilized GOx, a sensitive amperometric biosensor was developed for the
      detection of glucose up to 5.0 mM with a detection limit of 58 microM. The
      sensitivity increased with increasing sensing layers up to five bilayers.
      Ascorbic acid and uric acid did not cause any interference due to the use of a
      low operating potential. The present method showed high reproducibility for the
      fabrication of carbon-nanotubes-based amperometric biosensors.

PMID- 16430854
TI  - A Forster-resonance-energy transfer-based method for fluorescence detection of
      the protein redox state.
AB  - A method for fluorescence detection of a protein's redox state based on resonance
      energy transfer from an attached fluorescence label to the prosthetic group of
      the redox protein is described and tested for proteins containing three types of
      prosthetic groups: a type-1 copper site (azurin, amicyanin, plastocyanin, and
      pseudoazurin), a heme group (cytochrome c550), and a flavin mononucleotide
      (flavodoxin). This method permits one to reliably distinguish between reduced and
      oxidized proteins and to perform potentiometric titrations at submicromolar
      concentrations.

PMID- 16430855
TI  - [Rectal amputation by pure perineal approach with laparoscopic colostomy: a
      palliative therapeutic option for low rectal or anal cancers for elderly patients
      with multiple comorbidities].
AB  - Rectal syndrome caused by locoregional evolution of low rectal cancers and anal
      cancers is prevented and treated by surgical resection. But, for old patients
      with multiple tares, carcinologic surgical resection as abdominoperineal
      amputation can not be considered. Management of rectal syndrome becomes a
      therapeutic challenge. We reported a prospective serie of 5 patients more than 80
      years old with multiple tares, treated by rectal amputation by pure perineal
      approach with laparoscopic colostomy. This surgery avoided for all patients
      trying rectal symptoms and maintained acceptable quality of life with fast coming
      back at home. The palliative treatment of low rectal cancers or anal cancers
      combining rectal amputation by pure perineal approach with laparoscopic colostomy
      may be an interesting therapeutic option for patients who cannot undergoing
      aggressive carcinologic surgical treatment.

PMID- 16430856
TI  - Isolation and partial sequencing of cDNA clones from rat incisor after Nd:YAG
      laser irradiation in root canal.
AB  - OBJECTIVE: The purpose of this study was to identify the genes expressed in
      odontoblast-like cells and related to osteodentin production of pulp cells in
      vivo during the repair process. METHODS: A pulsed Nd:YAG laser was irradiated in
      mandibular incisors of rats at 2 W and 20 pulses/s for 5 s. We constructed a
      unidirectional cDNA library from the non-calcified portion of irradiated
      incisors, sequenced cDNA clones and classified their sequences by homology search
      through the GenBank database. RESULTS: Of the sequences determined, 26%
      represented sequences of new genes that were not related to any previously
      reported gene. 65.5% of the clones strongly matched genes and proteins in the
      databases. Among them, sequences found more than once were amelogenin,
      ameloblastin, amelin, collagen alpha1 type 1, osteonectin, nestin, enamelin and
      osteocalcin. Sequences detected only once were transforming growth factor beta-1
      (TGF-beta1), growth hormone receptor (Ghr), glypican, enamelysin (Mmp20), amelin
      2, integral membrane protein 2B, amelogenin precursor (Ame1), splicing factor 3b,
      insuline-like growth factor binding protein 5. CONCLUSION: This library reflects
      the gene expression during the dentin repair process in vivo including the
      odontoblast-like cell specific gene expression and osteodentin-production. Using
      this library, we indicate the candidate genes which might be related to
      odontoblast-differentiation and formation of osteodentin.

PMID- 16430857
TI  - A negative feedback system between brain serotonin systems and plasma active
      ghrelin levels in mice.
AB  - Brain serotonin (5-hydroxytryptamine; 5-HT) systems contribute to regulate eating
      behavior and energy homeostasis. 5-HT2C receptors and 5-HT1B receptors have been
      shown to mediate anorexic effects of 5-HT drugs such as d-fenfluramine, which
      stimulates 5-HT release and inhibits 5-HT reuptake, and m-chlorophenylpiperazine
      (mCPP), a 5-HT2C receptor agonist. Here, we report that 24-h fasting increased
      the expression of hypothalamic 5-HT2C receptor and 5-HT1B receptor genes in
      association with increases in plasma active ghrelin levels compared with fed
      state in mice. Treatment with mCPP or fenfluramine significantly inhibited the
      increases in plasma active ghrelin levels. mCPP or fenfluramine significantly
      increased the expression of hypothalamic pro-opiomelanocortin and cocaine- and
      amphetamine-regulated transcript genes while having no significant effects on the
      expression of hypothalamic neuropeptide Y, agouti- related protein, and ghrelin
      genes. These results suggest that there is a negative feedback system between
      brain 5-HT systems and plasma active ghrelin levels in energy homeostasis in
      mice.

PMID- 16430858
TI  - Dll4-selective Notch signaling induces ephrinB2 gene expression in endothelial
      cells.
AB  - The Notch pathway is involved in multiple aspects of vascular development,
      including arterial-venous differentiation. Here, we show that Notch stimulation
      instructively induces arterial characteristics in endothelial cells (EC). Forced
      expression of Notch intracellular domain (NICD, activated form of Notch) induced
      mRNA expression for a subset of arterial-specific markers such as ephrinB2,
      connexin40, and HERP1 only in EC but not other cell lines. In co-culture
      experiments using EC and either Dll4- or Jagged1-expressing cells, we found that
      Dll4 stimulation but not Jagged1 markedly induced ephrinB2 expression. An
      inducible expression of HERP1 and HERP2 by NICD has no measurable effects on
      expression of ephrinB2 and venous marker EphB4 although either HERP1 or HERP2
      overexpression exerts potent inhibitory effects on EphB4 expression without
      ephrinB2 induction. We also found no functional interaction between Notch and TGF
      beta-ALK1 signalings in an induction of ephrinB2 expression. These results
      suggest that Dll4-stimulated Notch signaling induces a part of arterial
      characteristics only in EC via HERP-independent mechanism. Our data provide new
      insight into the molecular mechanism of ligand-selective Notch activation during
      differentiation of arterial EC.

PMID- 16430859
TI  - Anti-fibrotic effects of theophylline on lung fibroblasts.
AB  - Theophylline has been used in the management of bronchial asthma and chronic
      obstructive pulmonary disease for over 50 years. It has not only a
      bronchodilating effect, but also an anti-inflammatory one conducive to the
      inhibition of airway remodeling, including subepithelial fibrosis. To date
      however, whether theophylline has a direct inhibitory effect on airway fibrosis
      has not been established. To clarify this question, we examined whether
      theophylline affected the function of lung fibroblasts. Theophylline suppressed
      TGF-beta-induced type I collagen (COL1) mRNA expression in lung fibroblasts and
      also inhibited fibroblast proliferation stimulated by FBS and TGF-beta-induced
      alpha-SMA protein. A cAMP analog also inhibited TGF-beta-induced COL1 mRNA
      expression in lung fibroblasts. A PKA inhibitor reduced the inhibitory effect of
      theophylline on TGF-beta-induced COL1 mRNA expression. These results indicate
      that theophylline exerts anti-fibrotic effects, at least partly, through the cAMP
      PKA pathway.

PMID- 16430860
TI  - Defects in a quinol oxidase lead to loss of KatC catalase activity in Pseudomonas
      aeruginosa: KatC activity is temperature dependent and it requires an intact
      disulphide bond formation system.
AB  - Mutation or overexpression of the cyanide-insensitive terminal oxidase (CIO) of
      Pseudomonas aeruginosa leads to temperature-sensitivity, multiple antibiotic
      sensitivity, and abnormal cell division and failure to produce a temperature
      inducible catalase [G.R. Tavankar, D. Mossialos, H.D. Williams, Mutation or
      overexpression of a terminal oxidase leads to a cell division defect and multiple
      antibiotic sensitivity in Pseudomonas aeruginosa, J. Biol. Chem. 278 (2003) 4524
      4530]. We identify this enzyme as KatC, a newly described catalase from P.
      aeruginosa. Loss of KatC activity leads to temperature-dependent hydrogen
      peroxide sensitivity, which correlates with its temperature-inducible expression
      pattern. This is the first description, to our knowledge, of a temperature
      inducible bacterial catalase. The transcription of katC is not affected in
      strains lacking or overexpressing the CIO, indicating that a post-transcriptional
      effect leads to loss of KatC activity. Disulphide bond formation is affected in
      strains lacking or overexpressing the CIO. This is shown by reduced activity of
      the extracellular enzymes lipase and elastase, and an altered pattern of redox
      states of DsbA, a key protein in disulphide bond formation in P. aeruginosa, in
      these strains. Moreover, a dsbA mutant had no detectable KatC activity,
      demonstrating that an intact disulphide bond formation system is required for
      KatC activity and thus explaining the loss of this catalase in the cio mutant and
      overexpressing strains.

PMID- 16430861
TI  - Expression of new human inorganic pyrophosphatase in thyroid diseases: its
      intimate association with hyperthyroidism.
AB  - Inorganic pyrophosphatase (PPase) controls the level of inorganic pyrophosphate
      produced by biosynthesis of protein, RNA, and DNA. Thus, PPase is essential for
      life. PPase expression is unclear in the thyroid. We cloned a new human PPase,
      phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPPase), and
      established a rabbit polyclonal anti-LHPPase antibody. This is the first study to
      determine the PPase expression by immunohistochemistry and Western blot.
      Intranuclear LHPPase expression of thyrocytes was enhanced most prominently in
      Graves' disease and autonomously functional thyroid nodule. To estimate a
      regulating factor of subcellular localization of LHPPase, we examined its
      expression of Graves' disease-derived thyrocytes in vitro with the disease
      originated serum. Nuclear expression of LHPPase was lost in cultured thyrocytes
      even with the serum, while its cytoplasmic expression was retained. The data
      suggest that increased expression of LHPPase is associated with hyperthyroidism.
      Intranuclear expression of LHPPase may not be regulated by Graves' disease
      derived serum factors.

PMID- 16430862
TI  - JWA, a novel signaling molecule, involved in the induction of differentiation of
      human myeloid leukemia cells.
AB  - Dysregulation of hematopoietic cellular differentiation contributes to
      leukemogenesis. Unfortunately, relatively little is known about how cell
      differentiation is regulated. JWA (AF070523) is a novel all-trans retinoic acid
      (ATRA) responsible gene that initially isolated from ATRA-treated primary human
      tracheal bronchial epithelial cells. For the notable performance achieved by ATRA
      in the differentiation induction therapy, we investigated the role of JWA in the
      induction of differentiation of human myeloid leukemia cells. Our results showed
      that JWA was not only regulated by ATRA but also by several other differentiation
      inducers such as phorbol-12-myristate-13-acetate (TPA), arabinoside (Ara-C), and
      hemin, involved in the mechanisms of differentiation along different lineages of
      myeloid leukemia cells arrested at different stages of development. Generally,
      JWA was up-regulated by these inducers in a time-dependent manner. Inhibition of
      JWA by RNA interference decreased the induced cellular differentiation. However,
      in NB4 cells treated with ATRA, dissimilar with others, the expression of JWA was
      down-regulated, and the induced cellular differentiation could be enhanced by
      silencing of JWA. Collectively, JWA works as a potential critical molecule,
      associated with multi-directional differentiation of human myeloid leukemia
      cells. In NB4 cells, JWA may function as a lineage-restricted gene during
      differentiation along the monocyte/macrophage-like or granulocytic pathway.

PMID- 16430863
TI  - Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy.
AB  - Severe Myoclonic Epilepsy in Infancy (SMEI) is an intractable epileptic syndrome
      with onset in the first year of life and is commonly caused by de novo mutations
      in the SCN1A gene, encoding the alpha1-subunit of the neuronal voltage-gated
      sodium channel. We report two unrelated families in which probands were affected
      by SMEI and their parents showed a single febrile seizure during early childhood
      or no neurological symptoms. Semiquantitative analysis of SCN1A mutations allowed
      the detection of a somatic and germline mosaicism in one of the parents. The
      study provides the first example of parental mosaicisms in SMEI and opens a new
      insight into the phenotypic variability and complex inheritance of this
      condition. The identification of germline mosaicisms has important consequences
      in genetic counseling of SMEI when SCN1A mutations appear to occur de novo with
      standard screening methods.

PMID- 16430864
TI  - Characterization of two trpE genes encoding anthranilate synthase alpha-subunit
      in Azospirillum brasilense.
AB  - The previous report from our laboratory has recently identified a new trpE gene
      (termed trpE2) which exists independently in Azospirillum brasilense Yu62. In
      this study, amplification of trpE(G) (termed trpE1(G) here) confirmed that there
      are two copies of trpE gene, one trpE being fused into trpG while the other trpE
      existed independently. This is the first report to suggest that two copies of the
      trpE gene exist in this bacterium. Comparison of the nucleotide sequence
      demonstrated that putative leader peptide, terminator, and anti-terminator were
      found upstream of trpE1(G) while these sequence features did not exist in front
      of trpE2. The beta-galactosidase activity of an A. brasilense strain carrying a
      trpE2-lacZ fusion remained constant at different tryptophan concentrations, but
      the beta-galactosidase activity of the same strain carrying a trpE1(G)-lacZ
      fusion decreased as the tryptophan concentration increased. These data suggest
      that the expression of trpE1(G) is regulated at the transcriptional level by
      attenuation while trpE2 is constantly expressed. The anthranilate synthase assays
      with trpE1(G)- and trpE2- mutants demonstrated that TrpE1(G) fusion protein is
      feedback inhibited by tryptophan while TrpE2 protein is not. We also found that
      both trpE1(G) and trpE2 gene products were involved in IAA synthesis.

PMID- 16430865
TI  - Identification of a new developmentally regulated Leishmania major large RAB
      GTPase.
AB  - Here, we describe for the first time a Leishmania specific gene encoding a large
      610 amino-acid RAB GTPase (LmLRAB). LmLRAB displays high homologies with the RAB
      GTPase protein family between amino acids 34 and 284. It contains characteristic
      signatures of RAB proteins: 4 GTP binding domains, 5 RAB specific domains, 3 RAB
      subfamily-specific domains, and a prenylation site. lmlrab is a single copy gene,
      transcribed as a 3.5 kb mRNA, highly conserved in Leishmania species, and encodes
      a protein doublet of approximately 75 kDa. Immunofluorescence microscopy using
      LmLRAB-specific antibodies demonstrated that LmLRAB is confined in a structure
      adjacent to the kinetoplast probably corresponding to an early endosomal/golgi
      apparatus localization. Interestingly, using quantitative real-time RT-PCR, we
      showed that the lmlrab gene is up-regulated twice in amastigotes relative to
      promastigotes. These findings suggest that LmLRAB may play a potential role in
      Leishmania pathogenicity.

PMID- 16430866
TI  - Identification of a nuclear matrix attachment region like sequence in the last
      intron of PI3Kgamma.
AB  - MARs are not only the structure bases of chromatin higher order structure but
      also have much biological significance. In this study, the whole sequence of
      about 100 kb in length from BAC clone of GS1-223D4 (GI: 5931478), in which human
      PI3Kgamma gene is localized, was analyzed by two online-based computer programs,
      MARFinder and SMARTest. A strong potential MAR was predicted in the last and
      largest intron of PI3Kgamma. The predicted 2 kb MAR, we refer to PIMAR, was
      further analyzed through biochemical methods in vitro and in vivo. The results
      showed that the PIMAR could be associated with nuclear matrices from HeLa cells
      both in vitro and in vivo. Further reporter gene analysis showed that in the
      transient transfection the expression of reporter gene linked with reversed PIMAR
      was repressed slightly, while in stably integrated state, the luciferase reporter
      both linked with reversed and orientated PIMAR was enhanced greatly in NIH-3T3
      and K-562. These results suggest that the PIMAR maybe has the capacity of
      shielding integrated heterogeneous gene from chromatin position effect. Through
      combination of computer program analysis with confirmation by biochemical
      methods, we identified, for the first time, a 2 kb matrix attachment region like
      sequence in the last intron of human PI3Kgamma.

PMID- 16430867
TI  - A synthetic defect in protein degradation caused by loss of Ufd4 and Rad23.
AB  - The UFD (ubiquitin fusion degradation) pathway is responsible for
      multiubiquitination of the fusion proteins that bear a "non-removable" N-terminal
      ubiquitin moiety. Previous reports have shown that the UFD pathway is conserved
      from yeast to human. The essential elements of the UFD pathway have also been
      identified in Saccharomyces cerevisiae. These studies, however, are limited to
      use of engineered UFD substrates. The biological significance of the UFD pathway
      remains unknown. Here we demonstrate that Ufd4, the E3 component of the UFD
      pathway, is involved in controlling the degradation of Rad4, a nucleotide
      excision repair protein. Moreover, simultaneous loss of Ufd4 and Rad23 exhibits a
      synthetic inhibitory effect on Rad4 degradation, presenting the first example
      that a UBA/UBL-domain protein functionally overlaps with a ubiquitin ligase in
      determining the turnover rate of a protein substrate. The current work also
      provides a direction for further investigation of the physiological functions of
      the UFD pathway.

PMID- 16430868
TI  - Loss of Pnn expression attenuates expression levels of SR family splicing factors
      and modulates alternative pre-mRNA splicing in vivo.
AB  - SR and SR-related proteins have been implicated as trans-acting factors that play
      an important role in splice selection and are involved at specific stages of
      spliceosome formation. A well-established property of SR protein splicing factors
      is their ability to influence selection of alternative splice sites in a
      concentration-dependent manner. Identification of molecules that regulate SR
      family protein expression is therefore of vital importance in RNA biology. Here
      we report that depletion of Pnn expression, a SR-related protein with functions
      involved in pre-mRNA splicing and mRNA export, induces reduced expression of a
      subset of cellular proteins, especially that of SR family proteins, including
      SC35, SRm300, SRp55, and SRp40, but not that of other nuclear proteins, such as
      p53, Mdm2, and ki67. Knocking down Pnn expression was achieved in vitro by siRNA
      transfection. Expression levels of SR and SR-related proteins in Pnn-depleted
      cells as compared to those in control cells were evaluated by immunofluorescent
      staining and Western blot with specific antibodies. In addition, we also
      demonstrate that loss of Pnn expression could modulate splice site selection of
      model reporter gene in vivo. Our finding is significant in terms of regulation of
      SR protein cellular concentration because it reveals that Pnn may play a general
      role in the control of the cellular amount of family SR proteins through down
      regulation of its own expression, thereby providing us with a better
      understanding of the cellular mechanism by which Pnn fulfills its biological
      function.

PMID- 16430870
TI  - Age-related alterations in GABA(A) receptor subunits in the nonhuman primate
      hippocampus.
AB  - Pharmacological studies have documented that altered drug responses, particularly
      to benzodiazepines, are common in elderly populations. While numerous factors may
      contribute to changes in drug response, age-related alterations in the molecular
      composition of GABA(A) receptors may be a key factor in regulating these
      responses. We employed quantitative densitometry to examine the cytological
      features and density of highly prevalent hippocampal GABA(A) receptor subunits
      (alpha1 and beta2/3) in young and aged rhesus monkeys. alpha1 and beta2/3 subunit
      immunostaining was differentially distributed throughout the hippocampus. In
      addition, beta2/3 immunolabeling in aged monkeys was characterized by marked
      intersubject variability in labeling intensity, with dramatic reductions present
      in 3 of 5 samples. alpha1 immunolabeling in aged monkeys was significantly
      reduced in the CA2 and CA3 subregions, and in hilus/polymorphic layer of the
      dentate gyrus. Collectively, our findings demonstrate that not only are GABA(A)
      receptor subunits differentially distributed throughout the hippocampus, but they
      are also differentially altered with increased age--changes that may have an
      important impact on the binding properties of GABA(A) receptor pharmacological
      agents.

PMID- 16430869
TI  - Agonist potency differentiates G protein activation and Ca2+ signalling by the
      orexin receptor type 1.
AB  - The G protein coupling characteristics of a flag epitope-tagged orexin receptor
      type 1 (OX1R) was investigated in HEK293 cells. Immunoprecipitation of the OX1R
      and immunoblotting revealed interactions with Gq/G11 proteins as well as with Gs
      and Gi proteins. Stimulation with orexin-A did not affect the ability of the OX1R
      to coprecipitate Gq/G11 proteins, but it robustly elevated the intracellular
      concentration of Ca2+, [Ca2+]i. No changes in cAMP levels could be detected upon
      receptor stimulation. To get further insight into the functional correlation of G
      protein activation and Ca2+ signalling, we used baculovirus transduction to
      express chimeric G proteins, containing the Galphas protein backbone with various
      Galpha donor sequences (Galphas/x) at the N and C termini, and measured cAMP as
      functional output. The Galphas/x chimeric proteins with Galpha11(Galphaq) and
      Galpha16 structure in the C terminus were stimulated by the OX1R. Concentration
      response curves with Galphas/16 revealed an agonist potency correlation between G
      protein activation and the elevation of [Ca2+]i via discharge of intracellular
      Ca2+ stores, a feature also recognized for the muscarinic M3 receptor. However,
      in contrast to the M3 receptor, the OX1R elevated [Ca2+]i via influx from
      extracellular space at about 30-fold lower agonist concentration. The results
      suggest that the OX1R is linked to influx of Ca2+ through a signal pathway
      independent of Gq/G11 protein activation.

PMID- 16430871
TI  - Sex differences in neuronal morphology in the killifish hypothalamus.
AB  - This study examined the neuroarchitecture of the male and female killifish
      (Fundulus heteroclitus) hypothalamus to evaluate whether sexual dimorphism of
      this brain region exists in fishes as it does in mammals and other vertebrates.
      The rostral medulla, a brain region distinct from the hypothalamic-pituitary
      gonadal axis, was also examined to determine if any observed differences were
      region-specific. With the use of Golgi-Cox impregnation, five dendritic
      characteristics were measured from neurons of both the hypothalamus and medulla
      including: spine density, number of branch points, dendrite length, surface area
      and volume. Dendritic spines are associated with excitatory synapses, and changes
      in density are associated with a variety of normal and pathological changes.
      Consistent with mammalian studies, we found that adult female killifish have 25%
      greater dendritic spine densities in the hypothalamus than male killifish
      (densities of 0.34+/-0.06 microm-1 and 0.25+/-0.08 microm-1, respectively). By
      contrast, no statistically significant difference between males and females was
      detected in spine densities in the rostral medulla. This finding supports the
      conclusion that hypothalamic sexual dimorphism is conserved in killifish.

PMID- 16430872
TI  - Dysmorphic neurons in patients with temporal lobe epilepsy.
AB  - We studied morphologic characteristics of dysmorphic neurons in the hippocampus
      of seven patients with medically intractable TLE and compare histological,
      clinical, and imaging features with ten TLE patients with classical hippocampal
      sclerosis without abnormal cells. Such dysmorphic neurons were observed in the
      hilus of the dentate gyrus and were characterized by giant or misshapen cells
      with abnormal cytoskeletal structure and atypical dendritic processes that
      resembled the dysmorphic neurons from cortical dysplasias. Specimens with
      dysmorphic cells also contained other cytoarchitectural abnormalities including
      bilamination of the dentate granular cell layer (four out seven cases), and the
      presence of Cajal-Retzius cells in the dentate gyrus or Ammon's horn (five out
      seven cases). There were no statistically significant differences regarding the
      age at onset, duration of epilepsy, and hippocampal asymmetry ratio between
      patients with or without dysmorphic cells. Nevertheless, it is interesting to
      note that a higher proportion of patients with dysmorphic neurons continued to
      present auras after surgery, when compared with patients without those cells.

PMID- 16430873
TI  - Fluorescent tagged analysis of neural gene function using mosaics in zebrafish
      and Xenopus laevis.
AB  - An important question in the neurosciences is the role of specific gene
      expression in the control of neural morphology and connectivity. To address this
      question, methods are needed for expression of exogenous genes in a subset of
      neurons. This limited and mosaic expression allows the assessment of gene
      expression in a cell autonomous fashion without environmental contributions from
      neighboring expressing cells. These methods must also label neurons so that
      detailed morphology and neural connections can be evaluated. The labeling method
      should label only a subset of neurons so that neuronal morphology can be viewed
      upon a non-stained background, in a Golgi staining fashion. Here, we report
      methods using plasmids called pTAGUM (tagged analysis of genes using mosaics)
      that accomplish these goals. These methods should prove useful for the analysis
      of neural gene function in two important model organisms, the zebrafish and
      Xenopus laevis.

PMID- 16430874
TI  - Antiobesity-like effects of the 5-HT2C receptor agonist WAY-161503.
AB  - WAY-161503 ((4aR)-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin
      5(6H)-one), a 5-HT(2B/C) receptor agonist, was characterized in vitro using
      stable Chinese hamster ovary cell lines expressing each of the human 5-HT2
      receptors and in vivo in animal models of obesity. WAY-161503 displaced both
      agonist ([125I]2,5-dimethoxy-4-iodoamphetamine (DOI)) and antagonist
      ([3H]mesulergine) radioligand binding to the human 5-HT2C receptor with derived
      Ki values of 3.3 +/- 0.9 and 32 +/- 6 nM, respectively. Relative to 5-HT2C
      receptor binding, WAY-161503 was approximately 6-fold less potent at human 5-HT2A
      receptors ([125I]DOI) with a derived Ki value of 18 nM and 20-fold less potent at
      human 5-HT2B receptors ([3H]5-HT) with a derived Ki value of 60 nM. In functional
      studies, WAY-161503 was a full agonist in stimulating 5-HT2C-receptor-coupled
      [3H]inositol phosphate (IP) formation and calcium mobilization with EC50 values
      of 8.5 nM and 0.8 nM, respectively. WAY-161503 was also a 5-HT2B agonist (EC50s
      of 6.9 and 1.8 nM for IP and calcium, respectively). In IP studies, WAY-161503
      was a weak 5-HT(2A) partial agonist (EC50, 802 nM) yet potently stimulated
      calcium mobilization (EC50, 7 nM) in 5-HT2A receptor-expressing cells.
      Functionally, WAY-161503 also stimulated the phospholipase A2-coupled arachidonic
      acid release in 5-HT2C receptor expressing cells albeit with lower potency (EC50,
      38 nM) and efficacy (Emax, 77%) compared with activation of the PLC pathway. In
      vivo, WAY-161503 produced dose-dependent decreases in 2-h food intake in 24 h
      fasted normal Sprague-Dawley rats, diet-induced obese mice, and obese Zuker rats
      with ED50 values of 1.9 mg/kg, 6.8 mg/kg, and 0.73 mg/kg, respectively. The
      reduction in food intake in normal Sprague-Dawley rats was reversed by
      administration of the 5-HT2C receptor antagonist SB-242084. Following chronic
      administration (10 days) in growing Sprague-Dawley rats, WAY-161503 decreased
      food intake and attenuated body weight gain. Finally, following chronic
      administration (15 days) of WAY-161503 to obese Zuker rats, the rats maintained a
      30% decrease in food intake over the 15-day period combined with a 25 g decrease
      in body weight relative to vehicle-treated controls demonstrating a lack of
      tolerance to its anorectic effects.

PMID- 16430875
TI  - Temporal and spatial distribution of immunoreactive PER1 and PER2 proteins in the
      suprachiasmatic nucleus and peri-suprachiasmatic region of the diurnal grass rat
      (Arvicanthis niloticus).
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus contains the primary
      circadian pacemaker in both diurnal and nocturnal mammals. The lower
      subparaventricular zone (LSPV) immediately dorsal to the SCN may also play an
      important role in the regulation of circadian rhythms. The SCN contains a
      multitude of oscillator cells that generate circadian rhythms through
      transcriptional/translational feedback loops involving a set of clock genes
      including per1 and per2. Little is known about the temporal and spatial features
      of the proteins encoded by these genes in day-active mammals. The first objective
      of this study was to characterize the expression of PER1 and PER2 in the SCN of a
      diurnal rodent, the unstriped Nile grass rat (Arvicanthis niloticus). The second
      objective was to evaluate the hypothesis that a molecular clock could exist in
      the LSPV, where endogenous rhythms in Fos expression are seen in grass rats but
      not in laboratory rats. Animals were kept on a 12:12 light/dark cycle and
      perfused at 4-h intervals, and their brains were processed for
      immunohistochemical detection of PER1 and PER2. Both proteins were seen in the
      SCN where they peaked early in the dark phase, providing further evidence that
      the differences between diurnal and nocturnal patterns of behavior emerge from
      mechanisms lying downstream from the pacemaker within the SCN. Rhythmic
      expression of PER1 and PER2 was also seen in the LSPV providing support for the
      hypothesis that this region might participate in circadian time keeping in the
      diurnal grass rat. In addition, rhythms were seen lateral to the LSPV and the
      SCN. Results of this study are discussed in light of similarities and differences
      in the circadian time-keeping systems of day- and night-active animals.

PMID- 16430876
TI  - Sucrose solution freezing studied by magnetic resonance imaging.
AB  - Ice formation of a 20% w/v sucrose solution was monitored during the freezing
      process by magnetic resonance imaging (MRI). An original experimental setup was
      designed with oil as a cooling fluid that allows accurate control of the
      temperature. The NMR signal intensity of particular sampled volumes was observed
      during the entire cooling period, from 0 to -50 degrees C, showing a peak
      characteristic to a transition before the loss of the signal. Moreover, spatial
      ice distribution of the frozen matrix was observed by high resolution MRI with an
      isotropic resolution of 78x78x78microm(3). MRI has proved to be a novel technique
      for determining the glass transition temperature of frozen sucrose solutions, in
      the concentration range where calorimetric measurements are not feasible.

PMID- 16430877
TI  - Reaction on D-glucal by an inverting phosphorylase to synthesize derivatives of 2
      deoxy-beta-D-arabino-hexopyranosyl-(1-->4)-D-glucose (2II-deoxycellobiose).
AB  - Four derivatives of 2(II)-deoxycellobiose were synthesized from d-glucal and
      acceptor sugars (d-glucose, d-xylose, d-mannose, and 2-deoxy-d-arabino-hexose)
      using a cellobiose phosphorylase from Cellvibrio gilvus. The enzyme was found to
      be an effective catalyst to synthesize the beta-(1-->4) linkage of 2-deoxy-d
      arabino-hexopyranoside. The acceptor specificity for the d-glucal reaction was
      identical to that for the alpha-d-glucose 1-phosphate reaction, but the activity
      of d-glucal was approximately 500 times less than that of alpha-d-glucose 1
      phosphate, using 10mM substrates.

PMID- 16430878
TI  - Protein kinase C alpha, betaI, and betaII isozymes regulate cytokine production
      in mast cells through MEKK2/ERK5-dependent and -independent pathways.
AB  - Regulation of MAPK pathways by PKC isoforms was examined in murine bone marrow
      derived mast cells (BMMCs). The PKCalpha, betaI, and betaII isoforms showed the
      most robust activation after FcepsilonR1-mediated stimulation by anti-ovalbumin
      specific IgE and ovalbumin (IgE-ova). PKCalpha, betaI, and betaII were all
      involved in activation of JNK, MEKK2, and ERK5, with differential relative
      contributions of each isoform to specific MAPK pathway components. BMMCs from
      mice lacking MEKK2 showed reduced production (50-60%) of IL-6, IL-13, and TNF
      alpha after stimulation, demonstrating MEKK2-dependent and -independent pathways
      for cytokine production. Cytokine production was stimulated by over-expression of
      PKC in cells from MEKK2-deficient and wild-type mice. Activation of ERK5 did not
      occur in BMMCs lacking MEKK2, indicating that MEKK2-independent cytokine
      production was also ERK5-independent. Since MAPK modules differentially regulate
      mast cell functions, including degranulation and cytokine production, it is
      suggested that specific functions could be targeted by inhibiting specific PKC
      isoforms.

PMID- 16430879
TI  - Free radicals, metals and antioxidants in oxidative stress-induced cancer.
AB  - Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along
      with reactive nitrogen species (RNS) are well recognised for playing a dual role
      as both deleterious and beneficial species. The "two-faced" character of ROS is
      substantiated by growing body of evidence that ROS within cells act as secondary
      messengers in intracellular signalling cascades, which induce and maintain the
      oncogenic phenotype of cancer cells, however, ROS can also induce cellular
      senescence and apoptosis and can therefore function as anti-tumourigenic species.
      The cumulative production of ROS/RNS through either endogenous or exogenous
      insults is termed oxidative stress and is common for many types of cancer cell
      that are linked with altered redox regulation of cellular signalling pathways.
      Oxidative stress induces a cellular redox imbalance which has been found to be
      present in various cancer cells compared with normal cells; the redox imbalance
      thus may be related to oncogenic stimulation. DNA mutation is a critical step in
      carcinogenesis and elevated levels of oxidative DNA lesions (8-OH-G) have been
      noted in various tumours, strongly implicating such damage in the etiology of
      cancer. It appears that the DNA damage is predominantly linked with the
      initiation process. This review examines the evidence for involvement of the
      oxidative stress in the carcinogenesis process. Attention is focused on
      structural, chemical and biochemical aspects of free radicals, the endogenous and
      exogenous sources of their generation, the metal (iron, copper, chromium, cobalt,
      vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g.
      Fenton chemistry), the DNA damage (both mitochondrial and nuclear), the damage to
      lipids and proteins by free radicals, the phenomenon of oxidative stress, cancer
      and the redox environment of a cell, the mechanisms of carcinogenesis and the
      role of signalling cascades by ROS; in particular, ROS activation of AP-1
      (activator protein) and NF-kappaB (nuclear factor kappa B) signal transduction
      pathways, which in turn lead to the transcription of genes involved in cell
      growth regulatory pathways. The role of enzymatic (superoxide dismutase (Cu, Zn
      SOD, Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants
      (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin
      and lipoic acid), flavonoids, selenium and others) in the process of
      carcinogenesis as well as the antioxidant interactions with various regulatory
      factors, including Ref-1, NF-kappaB, AP-1 are also reviewed.

PMID- 16430880
TI  - B-type natriuretic peptide in pediatrics.
AB  - OBJECTIVES: There has been growing interest in the use of serum B-type
      natriuretic peptide (BNP) and the N-terminal segment of its pro-hormone (NT
      proBNP) as biomarkers for cardiac disease. The aim of this review is to summarize
      the current state of knowledge regarding BNP and NT-proBNP measurement in the
      pediatric population. DESIGN AND METHODS: A computerized literature search on the
      National Library of Medicine was done and all articles including BNP and
      pediatrics were selected and discussed. RESULTS: The data from several studies
      suggest that the measurement of BNP may be useful in diagnosing and managing
      pediatric heart failure, congenital heart disease, cardiac transplantation and
      patients on chemotherapy. There are difficulties in establishing appropriate
      reference ranges in children. CONCLUSION: There is insufficient evidence for the
      routine use of BNP or NT-proBNP. Further research to clearly define the clinical
      utility in the pediatric age group is eagerly anticipated.

PMID- 16430881
TI  - Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect
      cardiac conduction system development.
AB  - The heterogeneous cell types of the cardiac conduction system are responsible for
      coordinating and maintaining rhythmic contractions of the heart. While it has
      been shown that the cells of the conduction system are derived from myocytes,
      additional cell types, including neural crest cells, may play a role in the
      development and maturation of these specialized cell lineages. Previous work has
      shown that the expression of the hf-1b gene is required for specification of the
      cardiac conduction system. Using Cre-Lox technology, we conditionally mutated the
      hf-1b gene in the ventricular and the neural crest cell lineages. Cx40
      immunohistochemistry on HF-1b tissue-restricted knockouts revealed a requirement
      for HF-1b in the cardiomyogenic lineage. Electrophysiological studies identified
      a second requirement for HF-1b in the neural crest-derived cells. Absence of HF
      1b in the neural crest led to atrial and atrioventricular dysfunction resulting
      from deficiencies in the neurotrophin receptor trkC. Therefore, in this study, we
      document that a single transcription factor, HF-1b, acts through two separate
      cell types to direct distinct functions of the cardiac conduction system.

PMID- 16430882
TI  - Discovery of vascular permeability factor (VPF).

PMID- 16430883
TI  - Silencing of LASP-1 influences zyxin localization, inhibits proliferation and
      reduces migration in breast cancer cells.
AB  - LIM and SH3 protein (LASP-1), initially identified from human breast cancer, is a
      specific focal adhesion protein involved in cell migration. LASP-1 is an actin
      binding protein, which also interacts with the proline-rich domains of zyxin, a
      scaffolding protein required for cell movement and gene transcription. In the
      present work, we analyzed the effect of LASP-1 on different human breast cancer
      cell lines. Transfection with LASP-1-specific siRNA resulted in a reduced protein
      level of LASP-1 in BT-20 and MCF-7 cell lines. The siRNA-treated cells were
      arrested in G2/M phase of cell cycle, and proliferation of the tumor cells was
      suppressed by 30-50% corresponding to around 50% of the cells being transfected
      successfully as seen by immunofluorescence. In addition, tumor cells showed a 50%
      reduced migration after siRNA treatment, while overexpression of LASP-1 in non
      tumor PTK-2 cells, which do not express endogenous LASP-1, resulted in a
      significant increase in cell motility. LASP-1 silencing is accompanied with a
      reduced binding of the of LASP-1 binding partner zyxin to focal contacts without
      changes in actin stress fiber organization as observed in immunofluorescence
      experiments. The data provide evidence for an essential role of LASP-1 in tumor
      cell growth and migration, possibly by influencing the localization of zyxin.

PMID- 16430884
TI  - Up-regulation of NFkappaB-responsive gene expression by DeltaNp73alpha in p53
      null cells.
AB  - Transactivation domain (TAD)-truncated p73, DeltaNp73, associates with p53,
      resulting in suppression of p53's functions. Using p53 null cell lines, we
      examined whether or not DeltaNp73 can regulate gene expression in a p53
      independent manner. When DeltaNp73alpha was co-transfected with a luciferase
      reporter plasmid with various enhancer elements, NFkappaB-responsive luciferase
      gene expression was selectively up-regulated by DeltaNp73alpha, but not by other
      p73-isoforms with TAD and DeltaNp73beta. Deletion of the TAD endowed p73alpha
      with the ability to enhance the responsive gene's expression, but deletion of the
      N-terminal proline-rich domain (PRD) rendered the TAD-deleted p73alpha inactive.
      Considering the inability of DeltaNp73beta, which is the C-terminus-truncated
      form of DeltaNp73alpha, to function, these results indicate that both the PRD and
      C-terminus are necessary for DeltaNp73alpha to can activate NFkappaB-responsive
      luciferase expression. Over-expression of p53 suppressed the TAD-truncated
      p73alpha-mediated luciferase expression, suggesting that p53 interferes with the
      TAD-truncated p73alpha-mediated activation of NFkappaB. Inhibitors for NFkappaB
      activation reduced the TAD-truncated p73alpha-dependent NFkappaB-responsive gene
      expression, indicating that TAD-truncated p73alpha activates NFkappaB as does
      TNFalpha. In addition to the results obtained in the reporter gene assay, TAD
      truncated p73alpha stimulated the translocation of NFkappaB to the nucleus and
      the expression of an endogenous NFkappaB-responsive gene, Bcl-XL. Taken together,
      these results demonstrate that TAD-truncated p73alpha can activate NFkappaB.

PMID- 16430885
TI  - Molecular cloning and characterization of Nop25, a novel nucleolar RNA binding
      protein, highly conserved in vertebrate species.
AB  - We report here the identification and characterization of a novel nucleolar RNA
      binding protein, referred to as Nop25 as based on its predicted molecular size
      and subcellular location. Nop25 homologues were widely discovered in diverse
      vertebrate species as hypothetical proteins, but not found in yeasts, plants and
      prokaryotic organisms. Nop25 was ubiquitously expressed in adult mouse organs and
      constitutively during mouse embryogenesis. Indirect immunofluorescence analysis
      with an anti-Nop25 antibody, as well as an experiment using a GFP-fused protein,
      demonstrated that Nop25 was localized in the nucleolus. Treatment of the cells
      with a low doses of actinomycin D caused Nop25 to translocate to the periphery of
      the nucleolus, suggesting that nucleolar localization of Nop25 is associated with
      rRNA transcription. Treatment of COS7 cells with RNase A resulted in a complete
      dissociation of Nop25 from the nucleolus, while in vitro binding assay
      demonstrated that Nop25 could bind directly to single-stranded nucleic acids.
      Further characterization of associated RNA molecules with Nop25 using
      immunoprecipitation experiment showed that Nop25 might bind to 28S rRNA. Studies
      on this novel nucleolar RNA binding protein may provide new information on the
      intricate nucleolar machinery as related to the transcription and processing of
      rRNA molecules and/or the subsequent assembly and maturation of ribosomes.

PMID- 16430886
TI  - Drug transport mechanisms in helminth parasites: passive diffusion of
      benzimidazole anthelmintics.
AB  - Anthelmintic molecules must reach their receptors inside target parasites to
      exert the pharmacological effect. Available data suggest that the main route of
      entry of antiparasitic drugs into helminth parasites would be through their
      external surface. However, it is unclear if trans-tegumental/cuticular
      penetration is the most important way of entry of benzimidazole (BZD)
      anthelmintics into their target parasites compared to oral ingestion. The
      relative involvement of active and passive transport mechanisms has not been
      defined. The goal of the work reported here was to determine the main processes
      involved in the entry of BZD anthelmintic molecules into the three main classes
      of helminth parasites. Adult specimens of Moniezia benedeni (cestode), Fasciola
      hepatica (trematode) and Ascaris suum (nematode) were incubated in Kreb's Ringer
      Tris buffer (pH 7.4, 37 degrees C) (1g parasite/10 ml incubation medium) for 15,
      45, and 90 min, respectively, in the presence of a concentration gradient of
      either fenbendazole (FBZ), oxfendazole or triclabendazole sulphoxide (TCBZSO) (1
      30 mol/ml, n=4). Dead helminth specimens were also incubated with the same drug
      concentration gradient. Specimens of F. hepatica with the oral route closed off
      by ligation were incubated with TCBZSO in the presence or absence of bovine serum
      albumin. After the incubation time elapsed, samples of parasite material were
      chemically extracted and prepared for high performance liquid chromatography
      analysis to measure drug/metabolite concentrations. Equivalent drug
      concentrations were measured within ligated and non-ligated liver flukes,
      demonstrating that BZD do mainly penetrate by trans-tegumental diffusion. The
      higher the concentration of BZD molecules in the incubation medium, the greater
      their concentration recovered within the helminth parasites. High correlation
      coefficients (>0.98) were obtained between initial drug concentration in the
      incubation medium and those measured inside the nematode, cestode, and trematode
      parasites. FBZ concentrations recovered from tissues of dead cestodes/nematodes
      over time were significantly greater compared to those measured in living
      parasites. These differences in drug diffusion may be related to the
      morphological/functional properties of the parasite's external surfaces. The
      outcome of the work reported here indicates that passive drug transfer through
      the external helminth surface is the main transport mechanism accounting for BZD
      accumulation into target parasites.

PMID- 16430887
TI  - Fasciola hepatica: effects on the antioxidative properties and lipid peroxidation
      of rat serum.
AB  - Fasciola hepatica infection is accompanied by increased formation of reactive
      oxygen species. The aim of this study was to analyze antioxidative properties of
      rat serum in the course of fasciolosis. Wistar rats were infected per os with 30
      metacercariae of F. hepatica. Activities of antioxidant enzymes and
      concentrations of non-enzymatic antioxidants in serum were determined at 4, 7,
      and 10 weeks post-infection (wpi). Activity of superoxide dismutase (Cu, Zn-SOD)
      significantly decreased (by 35% during the migratory phase, by 40 and 23% at 7
      and 10 wpi, respectively), while glutathione reductase activity significantly
      increased (by 62, 65, and 41%, at 4, 7, and 10 wpi, respectively). No significant
      changes were found in the activity of glutathione peroxidase. Significant
      decreases in concentrations of reduced glutathione, vitamins C, E, and A were
      observed, particularly during the migratory phase of fasciolosis (at 4 wpi).
      These changes were accompanied by enhancement of lipid peroxidation processes as
      evidenced by increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4
      HNE). Concentrations of MDA and 4-HNE at 4 wpi increased by 38% and by 59%. MDA
      increased by 51% at 7 wpi and by 79% at 10 wpi, while 4-HNE increased by 87 and
      118%, respectively. The results indicate that fasciolosis is associated with
      enhanced oxidative reactions and reduced antioxidant defense capability of rat
      serum.

PMID- 16430888
TI  - Plasmodium falciparum: chondroitin sulfate A is the major receptor for adhesion
      of parasitized erythrocytes in the placenta.
AB  - Plasmodium falciparum parasites that sequester in the placenta bind to the
      molecule chondroitin sulfate A (CSA). Women become resistant to malaria during
      pregnancy as they acquire antibodies that inhibit parasite adhesion to CSA,
      suggesting that a vaccine against placental malaria is feasible. Hyaluronic acid
      (HA) and non-immune IgG have also been proposed as receptors for P. falciparum
      adhesion in the placenta, but evidence for their roles is inconclusive. In this
      study, CSA, HA, and IgG were simultaneously assessed for their relative
      contributions to placental adhesion. Placental parasites collected in Tanzania
      uniformly adhered to the molecule CSA, and soluble CSA completely inhibited
      adhesion of most samples to placental cryosections. Three of 46 placental
      parasite samples also adhered to immobilized HA, but HA failed to inhibit
      adhesion of any placental parasites to placental cryosections. Similarly, non
      immune IgG and protein A failed to inhibit adhesion of parasite samples to
      placental cryosection. P. falciparum adhesion in the placenta appears to be a non
      redundant process that requires CSA as a receptor. Vaccines that elicit
      functional antibodies against CSA-binding parasites may confer resistance to
      pregnancy malaria.

PMID- 16430889
TI  - Heterogeneous PrPC metabolism in skeletal muscle cells.
AB  - Recent reports have shown that prions, the causative agent of transmissible
      spongiform encephalopathies, accumulate in the skeletal muscle of diseased
      animals and man. In an attempt to characterise in this tissue the prion protein
      (PrP(C)), whose conformational rearrangement governs the generation of prions, we
      have analysed the protein in primary cultured murine myocytes and in different
      skeletal muscle types. Our results indicate that the expression and cellular
      processing of PrP(C) change during myogenesis, and in muscle fibres with
      different contractile properties. These findings imply a potential role for
      PrP(C) in the skeletal muscle physiology, but may also explain the different
      capability of muscles to sustain prion replication.

PMID- 16430890
TI  - High phosphorylation of HBV core protein by two alpha-type CK2-activated cAMP
      dependent protein kinases in vitro.
AB  - Two alpha-type CK2-activated PKAs (CK2-aPKAIalpha and CK2-aPKAIIalpha) were
      biochemically characterized in vitro using GST-HBV core fusion protein (GST
      Hcore) and GST-Hcore157B as phosphate acceptors. It was found that (i), in the
      absence of cAMP, these two CK2-aPKAs phosphorylated both Ser-170 and Ser-178 on
      GST-Hcore and Hcore157B; (ii) this phosphorylation was approx. 4-fold higher than
      their phosphorylation by cAMP-activated PKAs; and (iii) suramin effectively
      inhibited the phosphorylation of Hcore157B by CK2-aPKAIIalpha through its direct
      binding to Hcore157B in vitro. These results suggest that high phosphorylation of
      HBV-CP by two CK2-aPKAs, in the absence of cAMP, may be involved in the
      pregenomic RNA (pgRNA) encapsidation and DNA-replication in HBV-infected cells.

PMID- 16430891
TI  - Sex differences in the organizational effects of corticosterone in the egg yolk
      of quail.
AB  - Previously, we found that experimentally elevated plasma corticosterone was
      transferred to egg yolk by female Japanese quail (Coturnix coturnix japonica),
      and that the chicks hatched from these eggs grew more slowly than controls and
      had higher responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis as
      adults. Here, we tested whether exposure to high yolk corticosterone was
      responsible for the slowed growth and elevated HPA responsiveness by manipulating
      the steroid content of eggs directly. Eggs were injected prior to incubation with
      a dose of corticosterone calculated to increase total yolk corticosterone
      concentration by two standard deviations. We found that elevated yolk
      corticosterone slowed growth in male but not female chicks and decreased the HPA
      responsiveness of female but not male adults, in contrast to the results of
      elevated corticosterone in laying females. Our results are consistent with others
      that demonstrate sex differences in the organizational effects of
      glucocorticoids. The mechanisms and adaptive value of such differences have yet
      to be determined.

PMID- 16430892
TI  - Prolactin and prolactin receptor expressions in a marine teleost, pufferfish
      Takifugu rubripes.
AB  - To investigate the physiological significance of prolactin (PRL) in a marine
      teleost, pufferfish (or fugu), Takifugu rubripes, we cloned and characterized
      cDNAs encoding its PRL and PRL receptor (PRLR) from the pituitary and gills,
      respectively. The fugu PRL cDNA consisted of 995 bp and encoded a protein of 213
      amino acids. The PRLR, consisting of 510 amino acids, contained a putative signal
      peptide, an extracellular domain with two pairs of cysteines, a WSXWS motif, a
      single transmembrane domain, and a cytoplasmic (intracellular) domain with box 1
      and box 2 regions, all of which are characteristic of the cytokine receptor
      superfamily. Reverse transcription-PCR showed the expression of PRLR mRNA in
      osmoregulatory organs, such as gills, kidney, and intestine, whereas pufferfish
      PRL mRNA was detected only in the pituitary. Furthermore, in situ hybridization
      revealed the expression of pufferfish PRLR in branchial chloride cells, kidney
      tubule cells, and intestinal epithelia. The PRL-gene expression levels in the
      pituitary were about five times higher in 25%-diluted seawater than in full
      strength seawater. These results suggest that fugu PRL regulates water and
      electrolyte balances through PRLR expressed in the osmoregulatory organs, as is
      the case with freshwater-adapted euryhaline species.

PMID- 16430893
TI  - Role of cathepsins in ovarian follicle growth and maturation.
AB  - Several complex processes are involved in the production of viable eggs. The aim
      of this review is to provide an overview on the role played by lysosomal enzymes,
      especially cathepsins B, D, and L, during ovarian follicle growth and maturation.
      Specific attention is focused on the relationship between the second proteolytic
      cleavage of yolk proteins (YP) and the resumption of the meiosis during germinal
      vesicle break down (GVBD). Maturation represents the final stage of oocytes
      development prior to ovulation. Oocytes in this phase appear translucent. In many
      teleosts GVBD is accompanied by water uptake and among marine teleosts with
      pelagic eggs, most of the final volume is reached by this process. The last phase
      of maturation in benthonic eggs also occurs concomitant to a second proteolytic
      cleavage and is related with a slight hydration process. In vitro maturation by
      17alpha,20beta-dihydroxy-4-pregnen-3one in class III Danio rerio oocytes, induced
      80% of GVBD. The maturation of these oocytes is known to be associated with
      proteolysis of their major yolk components. In the present study, we show that
      inhibition of specific enzymes (cathepsins) involved in the second YP processing,
      did not affect the occurrence of GVBD as the oocytes become translucent and
      display a slight increase in size. More specifically, in vitro incubation of the
      maturing oocytes with a cathepsin B inhibitor suppressed both cathepsin B and L
      activities and the proteolysis of YP. On the contrary, the addition of cathepsin
      L inhibitor, only affected cathepsin L activity, indicating that cathepsin B is
      probably involved in Cathepsin L activation, and this enzyme is probably
      responsible for the second YP processing. These results, together with previous
      studies, indicate that the GVBD process is independent of the occurrence of the
      second proteolytic process. It supports the hypothesis that the maturation
      process is under K+ ion flux control, while yolk proteolysis is related to the
      temporal and specific activation of cathepsins by acidification of yolk spheres.

PMID- 16430894
TI  - The fish endocrine pancreas: review, new data, and future research directions in
      ontogeny and phylogeny.
AB  - The literature on the ontogeny and phylogeny of the endocrine pancreas of ray
      finned fishes is summarized since the latest review in fish [Youson, J.H., Al
      Mahrouki, A.A., 1999. Review. Ontogenetic and phylogenetic development of the
      endocrine pancreas (islet organ) in fishes. Gen. Comp. Endocrinol. 116, 303-335].
      A basic description and a demonstration of the diversity of the fish islet organ
      is provided through new immunohistochemical data on islet tissue from a basal
      teleost, an osteoglossomorph, and a more derived teleost, a perciforme. Unlike
      the previous review, the present report provides a review and discussion of the
      utility of sequence data of insulin, somatostatin, and NPY- and glucagon-family
      peptides in phylogenetic analyses of jawed and jawless fishes. The present study
      also provides the first comparative analysis of sequences of preprohormones of
      endocrine peptides from closely related basal teleost species. Some nucleotide
      and deduced amino acid sequence data for preprosomatostatins (PPSS-I and/or -II)
      are compared for four species of bonytongues, Osteoglossomorpha, and with PPSSs
      of the white sucker, Catostomus commersoni, representing Cypriniformes, a more
      generalized teleost order. Phylogenetic analysis of deduced amino acid sequences
      of the PPSSs of these species and others from databases indicates good support
      for the monophyly of Osteoglossomorpha and some support for the present taxonomic
      grouping of the osteoglossomorphs examined, and also the white sucker. However,
      PPSS may have limited phylogenetic utility due to the relative short sequence,
      particularly in resolving relationships among lineages that diverged over a short
      period of time. Since in the few fish species examined we have just touched the
      surface in describing the diversity of structure of the islet organ, and likely
      the nature of the products of its cells, this report promotes the continued study
      of this organ.

PMID- 16430895
TI  - Clavicular hook plate for lateral end fractures:- a prospective study.
AB  - AIM: A prospective study was undertaken over a period of 4 years to evaluate the
      clinical and radiological outcomes following fixation with a clavicular hook
      plate for Neer types II and III fractures of lateral end clavicle. MATERIALS:
      Thirty-one patients (M:F; 24:7) with a mean age of 49 years (range 25-86 years)
      were recruited for the study. The mean follow-up duration was 40 months (range 18
      68 months). Twenty-three patients were treated primarily and eight patients were
      treated for symptomatic delayed union. RESULTS: All the patients achieved
      clinical and radiological union over a mean of 12 weeks (range 6-18 weeks). Mean
      constant score at and after 3 months was 94 (range 82-100). Mean ASES score at
      and after 3 months was 26 out of a maximum of 30. CONCLUSION: The clinical result
      of fracture fixation of lateral end clavicle using hook plate appeared good in
      terms of fracture union and function. The principal advantages of this method
      were anatomical reduction of the fracture and early rehabilitation which lead to
      good shoulder girdle function.

PMID- 16430897
TI  - Pregnancy outcomes in patients with previous history of abruptio placentae.

PMID- 16430896
TI  - Impact of pregnancy on primary dysmenorrhea.
AB  - OBJECTIVE: Because it has been observed that dysmenorrhea can improve after
      childbirth, this investigation was intended to quantify the impact of both
      gestational length and mode of delivery on primary dysmenorrhea. METHODS: This is
      an 8-year prospective observational study. Patients with a history of
      dysmenorrhea who later gave birth were evaluated for improvement on the severity
      of dysmenorrhea, with use of visual analogue scale (VAS), and Likert-type scale.
      RESULT: Final analysis involved 3694 patients. Women who had spontaneous delivery
      would have significantly more improvement than women with cesarean delivery per
      VAS (term delivery, 51 vs. 33, P<0.001; preterm delivery, 17 vs. 10, P<0.001).
      For first delivery, patients in the spontaneous delivery subgroup were the most
      likely to have improvement in severity of dysmenorrhea. For second delivery, only
      patients in the spontaneous delivery subgroup had statistically significant
      improvement. CONCLUSION: Both length of gestation and mode of delivery have an
      impact on primary dysmenorrhea. The most significant improvement occurred after
      the first delivery.

PMID- 16430898
TI  - Management of first trimester spontaneous abortion with 800 or 400 microg vaginal
      misoprostol.

PMID- 16430899
TI  - The effect of addressing demand for as well as supply of emergency obstetric care
      in Dinajpur, Bangladesh.
AB  - PURPOSE: The Dinajpur SafeMother Initiative (DSI) was designed to test the impact
      of several interventions on use of obstetric services in government health
      facilities in Northwestern Bangladesh during 1998-2001. INTERVENTION: Facility
      based interventions included upgrading health facilities. The sub-district
      hospitals or Upazila Health Centers (UHCs) had earlier been upgraded to provide
      basic emergency obstetric care (BEmOC). This project undertook activities
      designed to improved the quality of care in the facilities which included team
      building among providers, case reviews and a stakeholders' committee. CARE
      introduced a community mobilization intervention, which included birth planning,
      community support systems for funding, transportation, blood donation etc. for
      care of women with complications. METHODS: The intervention area received all
      interventions. The only intervention in the comparison area was the upgrading of
      the health facilities to provide basic EmOC. There were no interventions in the
      control area. RESULTS: Met need increased by 13% in comparison area but nearly
      24% in intervention area. There was no substantial change in the control area. At
      the end of the project, knowledge of obstetric danger signs was much greater in
      intervention area than in the other 2 areas. CONCLUSION: We conclude, therefore,
      that the best results are achieved through a combination of facility improvement,
      quality of care activities and targeted community mobilization activities.

PMID- 16430900
TI  - The expression of fractalkine in the endometrium during the menstrual cycle.
AB  - OBJECTIVE: The objective of the study was to evaluate the presence of fractalkine
      in the endometrium of the uterus and the change of fractalkine protein levels
      during menstrual cycle. METHODS: Twelve samples of endometrium of the uterus were
      obtained from gynecological patients who underwent total hysterectomy. Western
      blotting, RT-PCR and immunohistochemistry were performed. RESULTS: Fractalkine
      protein was detected in the endometrium of the uterus. Positive staining was
      confirmed in the epithelial cells and grandular cells in the endometrium.
      Expression levels of fractalkine protein and mRNA in the endometrium during
      secretory phase were significantly higher than those during proliferative phase.
      Immunohistochemical analysis using an anti-CX3CR1 antibody demonstrated positive
      staining in the glandular cells of the endometrium of the uterus. CONCLUSION:
      Fractalkine was expressed in the endometrium and its production was up-regulated
      during secretory phase.

PMID- 16430901
TI  - Vaginal vs. oral misoprostol for mid-trimester abortion.

PMID- 16430902
TI  - Nurses' response to pain communication from patients: a post-test experimental
      study.
AB  - BACKGROUND: Inadequate communication about pain can result in increased pain for
      patients. OBJECTIVES: The purpose of the current pilot study was to test how
      nurses respond when patients use their own words, a pain intensity scale, or both
      to communicate pain. DESIGN: A post-test only experimental design was used with
      three pain description conditions, personal and numeric; personal only; numeric
      only. SETTING: The setting included six hospitals and one school of nursing
      located in the northeastern United States. PARTICIPANTS: PARTICIPANTS included
      122 registered medical surgical nurses. METHODS: Nurses were randomly assigned to
      condition, and read a vignette about a trauma patient with moderately severe
      pain. The vignettes were identical except for the patient's pain description and
      age. The nurses then wrote how they would respond to the patient's pain. Two
      blind raters content analyzed the responses, giving nurses one point for
      including each of six a priori criteria derived from the Acute Pain Management
      Panel [1992. Acute Pain Management: operative or medical procedures and trauma.
      Clinical practice guideline (AHCPR Publication No. 92-0032)., Rockville, MD, USA]
      and the American Pain Society [2003. Principles of analgesic use in the treatment
      of acute pain and cancer pain, Glenville, IL, USA]. RESULTS: Nurses planned
      similar numbers of pain management strategies across the three conditions, with a
      mean of 2.1 (SD=1.14) strategies out of the recommended six. CONCLUSIONS: Nurses
      did not respond with more pain management strategies when patients describe pain
      in their own words, or in their own words and a pain intensity scale. The
      relatively small number of pain management strategies planned by the nurses
      suggests that nurses use few strategies to respond to moderately severe pain
      problems.

PMID- 16430903
TI  - Metabolic syndrome, low-density lipoprotein cholesterol, and risk of
      cardiovascular disease: a population-based study.
AB  - We sought to examine the relative contribution to cardiovascular risk of the
      metabolic syndrome (MS) compared with that of a high LDL cholesterol level in a
      population-based study of 2493 men and women, age 41-72 years, without major
      cardiovascular diseases at baseline. MS was defined according to the National
      Cholesterol Education Program criteria. The study population was subdivided into
      four groups on the basis of presence (prevalence: 15%) or absence of MS (85%) and
      presence (15%) or absence of high LDL cholesterol (85%) defined as a level >5.02
      mmol/L or </=5.02 mmol/L. After 9.5 years, 233 had a cardiovascular endpoint
      (cardiovascular death, ischemic heart disease, and stroke). In proportional
      hazard models, adjusting for age, sex, and smoking, and with subjects without MS
      and LDL cholesterol </=5.02 mmol/L as reference (73%), the relative risk of an
      endpoint (95% CI) was 1.49 (1.04-2.13) in participants without MS and LDL
      cholesterol >5.02 mmol/L (12%), 1.80 (1.26-2.57) in subjects with MS and LDL
      cholesterol </=5.02 mmol/L (12%) and 3.21 (1.99-5.17) in participants with both
      MS and LDL cholesterol >5.02 mmol/L (3%). In a general population, MS was
      associated with a cardiovascular risk comparable with that of a high LDL
      cholesterol level.

PMID- 16430904
TI  - Association between well-characterized lipoprotein-related genetic variants and
      carotid intimal medial thickness and stenosis: The Framingham Heart Study.
AB  - OBJECTIVE: To determine the association of well-characterized lipoprotein-related
      genetic variants with carotid intimal medial thickness (IMT) and stenosis.
      METHODS: 3380 men and women from the Framingham Offspring Study underwent carotid
      ultrasound to determine carotid IMT and stenosis>/=25%. We genotyped 12 variants
      in 10 lipoprotein-related genes known to be associated with significant
      differences in lipoprotein levels. RESULTS: For most of the variants, there was
      no association with carotid IMT. In multivariable, sex-specific analyses, the
      rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was
      associated with lower ICA IMT in men. Hypertension was associated with higher ICA
      IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for
      the interaction=0.041). In analyses of carotid stenosis in male, carriers of the
      lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid
      stenosis (OR=2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN
      genotype. CONCLUSIONS: While there is no evidence for a significant association
      of several common lipoprotein-related genetic variants with carotid IMT, our
      results are consistent with the previously reported role of CETP and LPL genetic
      variants in cardiovascular risk and the possible modulation of the association
      between hypertension and carotid IMT by APOCIII Sst-1 variant.

PMID- 16430905
TI  - Alternative approach to modal gait analysis through the Karhunen-Loeve
      decomposition: An application in the sagittal plane.
AB  - This article uses the Karhunen-Loeve decomposition (KL) technique, also known as
      proper orthogonal decomposition (POD) or principal component analysis (PCA), to
      introduce the concept of gait mode, which can be used as a tool to identify gait
      differences among subjects or groups and to approximate gait curves. The KL is a
      statistical pattern analysis technique for finding dominant structures in an
      ensemble of data. This technique can be used to decompose a spatiotemporal signal
      into time-independent, orthogonal, spatial components and time-dependent
      amplitudes. This study demonstrates the existence of a common gait mode through
      the analysis of the kinematics of 57 young, healthy subjects, and how they can be
      used to identify different walking patterns, for instance differentiating male
      and female subjects.

PMID- 16430906
TI  - Quantitative impurity profiling by principal component analysis of high
      performance liquid chromatography-diode array detection data.
AB  - Related organic impurities generally have approximately similar molar absorption
      coefficients (epsilon) due to their structural similarities. On the assumption
      that all peaks in an impurity profiling chromatogram have approximately the same
      maximum molar absorption coefficients (epsilon(max)) and the chromatogram
      contains one major peak and several much smaller ones, all of which are
      completely separated, integration of the summed score vectors from the principal
      component analysis (PCA) decomposition of high-performance liquid chromatography
      diode array detection (HPLC-DAD) data will give areas that are quantitatively
      proportional to the actual content of the compounds. Due to the sequential nature
      of PCA, the first principal component (PC) will primarily be related to the main
      compound and all peaks showing a similar spectrum, while the second PC will be
      related to the impurities with a spectrum different from the main peak. Summing
      the two score vectors thus makes it possible to take account of different spectra
      in the score chromatogram, which make the method proposed give better
      quantitative estimates of the impurities than any single wavelength chromatogram.
      Multivariate curve resolution alternating least squares (MCR-ALS) is used for
      comparison. The results are presented for two examples of simulated HPLC-DAD data
      as well as for three examples of real HPLC-DAD data from impurity profiling. The
      results show that integration of the score chromatograms can handle differences
      in the unknown epsilon(max) of the peaks and take account of the different
      spectra of the impurity peaks, giving quantitative estimates of the content of
      the impurities that closely correspond to the reference values. The results
      obtained are also better than integration with the best possible separate
      wavelength. The method could be a straightforward approach to impurity profiling
      in order to obtain a good estimate of the content or relative response factors of
      small chromatographic impurity peaks without knowledge of their molar absorption
      coefficients and without any precalibration.

PMID- 16430907
TI  - Alternative moving window factor analysis for comparison analysis between complex
      chromatographic data.
AB  - In this investigation, a novel chemometric method is developed for the analysis
      of five possible relationships of components or spectral features between two
      correlative but different hyphenated chromatographic systems. It is very helpful
      for comparison study of components present in different complex systems in both
      chemistry and systems biology. The proposed method, named alternative moving
      window factor analysis (AMWFA), could be utilized to determine the number of
      common components between different samples and then to identify their
      corresponding spectra half-automatically. AMWFA can alternatively be employed to
      mind for the selective information hiding in anyone of the two compared data X
      and Y, and to self-verify the resolution results by changing the extracted target
      matrices in analysis. From the results of comparison of simulated hyphenated
      chromatographic data, volatile chemical components in drug pair rhizoma ligustici
      chuanxiong-radix paeoniae rubra (RLC-RPR) and its single herbal medicines, and
      analysis of Angelica oral solution and its plasma sample after oral intake to
      rabbit, powerful ability of the proposed method is shown.

PMID- 16430908
TI  - Analysis of nephroloxic and carcinogenic aristolochic acids in Aristolochia
      plants by capillary electrophoresis with electrochemical detection at a carbon
      fiber microdisk electrode.
AB  - Aristolochic acids (AAs) are the main bioactive ingredients in the most of
      Aristolochia plants, which are used to make dietary supplements, slimming pills
      and Traditional Chinese Medicines (TCMs). Excessive ingestion of AAs can lead to
      serious nephropathy. Therefore, quantitative analysis and quality control for the
      plants containing AAs is of great importance. In this paper, capillary
      electrophoresis (CE) with electrochemical detection (ED) at a 33 microm carbon
      fiber microdisk electrode (CFE) has been applied to detect AA-I and AA-II in
      Aristolochia plants. Under the optimum conditions: detection potential at 1.20 V,
      2.0 x 10(-2) mol L(-1) phosphate buffer solution (PBS) (pH 10.0), injection time
      25 s at a height of 17 cm and separation voltage at 12.5 kV, the AA-I and AA-II
      were baseline separated within 5 min. Low detection limits for AA-I and AA-II
      were 4.0 x 10(-8) mol L(-1) and 1.0 x 10(-7) mol L(-1), respectively. Wide linear
      ranges were from 4.0 x 10(-8) mol L(-1) to 1.9 x 10(-5) mol L(-1) and 1.0 x 10(
      7) mol L(-1) to 5.0 x 10(-5) mol L(-1) for AA-I and AA-II, respectively. The
      proposed method has been successfully applied to analyze AAs contents in plant
      extracts. The results indicated that the contents of AAs in each part of
      Aristolochia debilis Sieb. Et Zucc. plant were different. Meanwhile, the CE-ED
      method was utilized for fingerprint analysis of medicine herbs. Six herbs (Radix
      aristolochiae, Fructus aristolochiae, Herba aristolochiae, Caulis aristolochiae
      manshuriensis, Caulis clematidis armandii, Caulis akebiae) were well
      distinguished by comparing their electropherograms obtained by CE-ED method.

PMID- 16430909
TI  - Simplified pesticide multiresidue analysis in virgin olive oil by gas
      chromatography with thermoionic specific, electron-capture and mass spectrometric
      detection.
AB  - In the present work, an analytical multiresidue method has been developed for the
      analysis of 32 organochlorine, organophosphorus and organonitrogen pesticides at
      microg kg(-1) levels in virgin olive oil. The method consists of the extraction
      of the pesticides with acetonitrile saturated in n-hexane followed by a clean-up
      process based on gel permeation chromatography (GPC) with ethyl acetate
      ciclohexane (1:1) as mobile phase to separate the low-molecular mass pesticides
      from the high-molecular mass fat constituents of the oil. The target compounds
      were determined in the final extract by gas chromatography (GC) using thermoionic
      specific (TSD) and electron-capture (ECD) detection. In the case of positive
      samples, the amounts found were confirmed by GC-MS/MS, being the results in good
      agreement. Recoveries and RSDs (n = 10) values were 91-124% and 1-8% (GC-ECD), 82
      100% and 9-20% (GC-TSD), and 89-105% and 4-14% (GC-MS/MS), respectively. The
      three proposed methods were applied to samples collected directly in two olive
      mills located in the Jaen province (Spain). Specifically, 24 samples of virgin
      olive oil were collected. The most frequently pesticide residues found were the
      herbicides terbuthylazine and diuron and endosulfan sulfate, a degradation
      product of the insecticide endosulfan. The herbicide concentration was higher in
      those oil samples obtained from olives which were collected from the ground after
      they had fallen down than in those oil samples from olives harvested directly
      from the tree. The GC-MS/MS developed method was also applied to the analysis of
      an olive oil sample from a proficiency test spiked with organochlorine pesticides
      and all the values obtained were within the specified "satisfactory" range.

PMID- 16430910
TI  - High-performance liquid chromatographic stationary phases based on polysiloxanes
      with different chain lengths thermally immobilized on silica supports.
AB  - Reversed phases for high-performance liquid chromatography (RP-HPLC) were
      obtained by thermal immobilization of polysiloxanes having different length
      chains (C1, C8 and C14) onto HPLC silica particles. The importance both of
      percent loading of the stationary phase promoted by each immobilization procedure
      and of the length of the lateral chain of the polymer on the chromatographic
      performances of the phases obtained is compared and discussed.

PMID- 16430911
TI  - An efficient diethyl ether-based soxhlet protocol to quantify faecal sterols from
      catchment waters.
AB  - A study was conducted to evaluate the efficiency and reproducibility of a diethyl
      ether-based soxhlet extraction procedure for faecal sterols occurring from
      catchment waters. Water samples spiked with a mixture of faecal sterols were
      filtered and analytes were extracted using the diethyl ether-based soxhlet method
      and the Bligh and Dyer chloroform extraction process. For diethyl ether-based
      soxhlet extraction procedure, solvent extracts were saponified with 100 microL of
      10% KOH in methanol (100 degrees C/120 min) and then acidified with 60 microL of
      6M HCl. Lipid contents were extracted by ethanol (0.5 mL) from the saponification
      products. The lipid extracts were then reacted with 100 microL of
      bis(trimethyl)trifluoroacetamide (BSTFA) containing 1% trimethyl chlorosilane
      (100 degrees C/60 min) to form the trimethylsilyl (TMS) derivatives. The
      derivatised extracts were then analyzed by gas chromatography-mass spectrometry.
      For sterol concentrations ranging from 35 to 175 microg mL(-1), the soxhlet-based
      extraction process yielded the following recovery efficiencies for coprostanol
      (101%), epicoprostanol (97%), cholesterol (97%), dihydrocholesterol (97%) and
      5alpha-cholestane (111%), whereas the Bligh and Dyer process yielded recoveries
      of 32, 41, 0, 36 and 51%, respectively. The results suggested that the diethyl
      ether-based soxhlet extraction method was more efficient and reproducible than
      the Bligh and Dyer chloroform extraction process for the analyses of trace levels
      of faecal sterols from water samples. Moreover, it was revealed that the diethyl
      ether-based soxhlet extraction method used less solvent and was logistically
      easier.

PMID- 16430913
TI  - Transport coefficients and orientational distributions of spheroidal particles
      with magnetic moment normal to the particle axis (Analysis for an applied
      magnetic field normal to the shear plane).
AB  - We have investigated the influence of the magnetic field strength, shear rate,
      and rotational Brownian motion on transport coefficients such as viscosity and
      diffusion coefficient, and also on the orientational distributions of rodlike
      particles of a dilute colloidal dispersion. The rodlike particle is modeled as a
      magnetic spheroidal particle which has a magnetic moment normal to the particle
      axis; such a particle may typically be a hematite particle. In the present study,
      an external magnetic field is applied in the direction normal to the shear plane
      of a simple shear flow. The basic equation of the orientational distribution
      function has been derived from the balance of torques and solved numerically. The
      results obtained here are summarized as follows. Although the orientational
      distribution function shows a sharp peak in the shear flow direction for a very
      strong magnetic field, such a peak is not restricted to the field direction
      alone, but continues in every direction of the shear plane. This is due to the
      characteristic particle motion that the particle can rotate around the axis of
      the magnetic moment in the shear plane, although the magnetic moment nearly
      points to the magnetic field direction. This particle motion in the shear plane
      causes negative values of the viscosity due to the magnetic field. The viscosity
      decreases, attains a minimum value, and then converges to zero as the field
      strength increases. Additionally, the diffusion coefficient is significantly
      influenced by such characteristic particle motion in the shear plane for a strong
      magnetic field.

PMID- 16430912
TI  - Effect of surface hydrophobicity/hydrophilicity of mesoporous supports on the
      activity of immobilized lipase.
AB  - Taking advantage of the virtue of hydrophilic surface, lipase was firstly
      immobilized on SBA-15 as a support. Then the surface of the SBA-15 with enzyme
      entrapped inside the channels was modified by grafting with organic moieties. It
      has been found that the silylation with n-decyltrimethoxysilane (DE) and 3
      (trimethoxysilyl)propyl methacrylate (MA) following the lipase immobilization
      increases the surface hydrophobicity. But the surface modified by MA shows more
      hydrophilicity than that modified by DE. The activity assay indicates that the
      hydrolytic activity for the hydrolysis of insoluble or partly soluble substrates
      increases with enhanced surface hydrophobicity.

PMID- 16430914
TI  - C-reactive protein activates the nuclear factor-kappaB pathway and induces
      vascular cell adhesion molecule-1 expression through CD32 in human umbilical vein
      endothelial cells and aortic endothelial cells.
AB  - C-reactive protein (CRP) contributes to the process of atherosclerosis by
      inducing pro-inflammatory changes in endothelial cells. However, the exact
      receptor involved in CRP-induced endothelial changes remains unclear. Human
      umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells
      (HAECs) were used for the experiments. After incubation with CRP, immunoblotting
      showed a significant decrease of IkappaB protein and electrophoretic mobility
      shift assay showed a significant increase of nuclear NF-kappaB binding capacity.
      These changes were associated with a significant increase of vascular cell
      adhesion molecule-1 (VCAM-1) expression. The mRNA level of CD32, the major
      binding protein for CRP in endothelial cells, increased significantly as measured
      by Northern blot and Western blot. When these cells were transfected with siRNA
      directed against CD32, the mRNA of CD32 decreased significantly. The IkappaB
      degradation, NF-kappaB nuclear translocation and VCAM-1 up-regulation induced by
      CRP were all inhibited by treatment with siRNA against CD32. SB203580, a P38
      inhibitor, significantly attenuated the CRP-induced responses while SP600125 (c
      jun kinase inhibitor) did not. In conclusion, CRP-induced IkappaB degradation, NF
      kappaB nuclear translocation and VCAM-1 protein expression in HUVECs and HAECs.
      CRP also increased the expression of CD32, which might serve as the receptor for
      CRP in endothelial cells and mediated the effects of CRP.

PMID- 16430915
TI  - Metaboelectric signaling in the diseased heart.

PMID- 16430916
TI  - Structure of the regulatory apparatus of a calcium-dependent protein kinase
      (CDPK): a novel mode of calmodulin-target recognition.
AB  - Calcium-dependent protein kinases (CDPKs) are a class of calcium-binding sensory
      proteins that are found in plants and certain protozoa, including the causative
      agent of malaria, Plasmodium falciparum. CDPKs have diverse regulatory functions,
      including involvement in the triggering of the lytic cycle of malarial infection.
      CDPKs contain an autoinhibitory junction (J) region whose calcium-dependent
      interaction with the tethered regulatory calmodulin-like domain (CaM-LD)
      activates the catalytic kinase domain. We report here the X-ray crystal structure
      of the J-CaM-LD region of CDPK from Arabidopsis thaliana (AtCPK1), determined to
      2.0 A resolution using multiple-wavelength anomalous dispersion (MAD). The
      structure reveals a symmetric dimer of calcium-bound J-CaM-LD with domain-swap
      interactions, in which the J region of one protomer interacts extensively with
      the carboxy-terminal EF-hand domain (C-lobe) of the partner protomer. However, as
      the J-CaM-LD is monomeric in solution, the activated monomer was modelled to
      account for the intra-molecular recognition of the two domains. While the J-CaM
      LD segment mimics certain aspects of target motif recognition by CaM other
      features are specific to CDPKs, in particular the combination of the strong
      interaction between the N and C-lobes of the CaM-LD and the exclusive use of only
      the C-lobe in the recognition of the covalently tethered target region. Combined
      with our previous observations showing that there is likely to be strong
      interactions between this tethered J region and the CaM-LD even at basal Ca(2+)
      concentrations, the new structural data indicate that the response to calcium of
      CDPKs is clearly unique among the CaM family.

PMID- 16430917
TI  - Structure of the alpha-actinin-vinculin head domain complex determined by cryo
      electron microscopy.
AB  - The vinculin binding site on alpha-actinin was determined by cryo-electron
      microscopy of 2D arrays formed on phospholipid monolayers doped with a nickel
      chelating lipid. Chicken smooth muscle alpha-actinin was cocrystallized with the
      beta1-integrin cytoplasmic domain and a vinculin fragment containing residues 1
      258 (vinculin(D1)). Vinculin(D1) was located at a single site on alpha-actinin
      with 60-70% occupancy. In these arrays, alpha-actinin lacks molecular 2-fold
      symmetry and the two ends of the molecule, which contain the calmodulin-like and
      actin binding domains, are held in distinctly different environments. The
      vinculin(D1) difference density has a shape very suggestive of the atomic
      structure. The atomic model of the complex juxtaposes the alpha-actinin binding
      site on vinculin(D1) with the N-terminal lobe of the calmodulin-like domain on
      alpha-actinin. The results show that the interaction between two species with
      weak affinity can be visualized in a membrane-like environment.

PMID- 16430918
TI  - Structural basis of the nucleotide driven conformational changes in the AAA+
      domain of transcription activator PspF.
AB  - Bacterial enhancer-binding proteins (EBP) activate transcription by hydrolyzing
      ATP to restructure the sigma(54)-RNA polymerase-promoter complex. We compare six
      high resolution structures (<2.1 A) of the AAA(+) domain of EBP phage shock
      protein F (PspF) including apo, AMPPNP, Mg(2+)-ATP, and ADP forms. These
      structures permit a description of the atomic details underpinning the origins of
      the conformational changes occurring during ATP hydrolysis. Conserved regions of
      PspF's AAA(+) domain respond distinctively to nucleotide binding and hydrolysis,
      suggesting functional roles during the hydrolysis cycle, which completely agree
      with those derived from activities of PspF mutated at these positions. We propose
      a putative atomic switch that is responsible for coupling structural changes in
      the nucleotide-binding site to the repositioning of the sigma(54)-interacting
      loops. Striking similarities in nucleotide-specific conformational changes and
      atomic switch exist between PspF and the large T antigen helicase, suggesting
      conservation in the origin of those events amongst AAA(+) proteins.

PMID- 16430919
TI  - Crystal structure of protein Ph1481p in complex with protein Ph1877p of archaeal
      RNase P from Pyrococcus horikoshii OT3: implication of dimer formation of the
      holoenzyme.
AB  - Ribonuclease P (RNase P) in the hyperthermophilic archaeon Pyrococcus horikoshii
      OT3 consists of a catalytic RNA and five protein subunits. We previously
      determined crystal structures of four protein subunits. Ph1481p, an archaeal
      homologue for human hPop5, is the protein component of the P.horikoshii RNase P
      for which no structural information is available. Here we report the crystal
      structure of Ph1481p in complex with another protein subunit, Ph1877p, determined
      at 2.0 A resolution. Ph1481p consists of a five-stranded antiparallel beta-sheet
      and five helices, which fold in a way that is topologically similar to the
      ribonucleoprotein (RNP) domain. Ph1481p is, however, distinct from the typical
      RNP domain in that it has additional helices at the C terminus, which pack
      against one face of the beta-sheet. The presence of two complexes in the
      asymmetric unit, together with gel filtration chromatography indicates that the
      heterotetramer is stable in solution and represents a fundamental building block
      in the crystals. In the heterotetrameric structure (Ph1877p-(Ph1481p)(2)
      Ph1877p), a homodimer of Ph1481p sits between two Ph1877p monomers. Ph1481p
      dimerizes through hydrogen bonding interaction from the loop between alpha1 and
      alpha2 helices, and each Ph1481p interacts with two Ph1877p molecules, where
      alpha2 and alpha3 in Ph1481p interact with alpha7 in one Ph1877p and alpha8 in
      the other Ph1877p molecule, respectively. Deletion of the alpha1-alpha2 loop in
      Ph1481p caused heterodimerization with Ph1877p, and abolished ability to
      homodimerize itself and heterotetramerize with Ph1877p. Furthermore, the
      reconstituted particle containing the deletion mutant Ph1481p (mPh1481p)
      exhibited significantly reduced nuclease activity. These results suggest the
      presence of the heterotetramer of Ph1481p and Ph1877p in P.horikoshii RNase P.

PMID- 16430920
TI  - The denatured state under native conditions: a non-native-like collapsed state of
      N-PGK.
AB  - The guanidinium-denatured state of the N-domain of phosphoglycerate kinase (PGK)
      has been characterized using solution NMR. Rather than behaving as a homogenous
      ensemble of random coils, chemical shift changes for the majority of backbone
      amide resonances indicate that the denatured ensemble undergoes two definable
      equilibrium transitions upon titration with guanidinium, in addition to the major
      refolding event. (13)C and (15)N chemical shift changes indicate that both
      intermediary states have distinct helical character. At denaturant concentrations
      immediately above the mid-point of unfolding, size-exclusion chromatography shows
      N-PGK to have a compact, denatured form, suggesting that it forms a helical
      molten globule. Within this globule, the helices extend into some regions that
      become beta strands in the native state. This predisposition of the denatured
      state to extensive non-native-like conformation, illustrates that, rather than
      directing folding, conformational pre-organization in the denatured state can
      compete with the normal folding direction. The corresponding reduction in control
      of the direction of folding as proteins become larger, could thus constitute a
      restriction on the size of protein domains.

PMID- 16430921
TI  - Identification of the amino acid residues rendering TI-VAMP insensitive toward
      botulinum neurotoxin B.
AB  - Botulinum neurotoxins types B, D, F, and G, and tetanus neurotoxin inhibit
      vesicular fusion via proteolytic cleavage of VAMP/Synaptobrevin, a core component
      of the membrane fusion machinery. Thus, these neurotoxins became widely used
      tools for investigating vesicular trafficking routes. Except for VAMP-1, VAMP-2,
      and Cellubrevin, no other member of the VAMP family represents a substrate for
      these neurotoxins. The molecular basis for this discrepancy is not known. A 34
      amino acid residue segment of VAMP-2 was previously suggested to mediate the
      interaction with botulinum neurotoxin B, but the validity of the data was later
      questioned. To check whether this segment alone controls the susceptibility
      toward botulinum neurotoxin B, it was used to replace the corresponding segment
      in TI-VAMP. The resulting VAMP hybrid and VAMP-2 were hydrolysed at virtually
      identical rates. Resetting the VAMP-2 portion in the hybrid from either end to TI
      VAMP residues gradually reduced the cleavability. A hybrid encompassing merely
      the VAMP-2 segment 71-80 around the Gln76/Phe77 scissile bond was still
      hydrolysed, albeit at a approximately tenfold lower cleavage rate. The
      contribution of each non-conserved amino acid of the whole 34-mer segment to the
      interaction was investigated employing VAMP-2. We find that the eight non
      conserved residues of the 71-80 segment are all necessary for efficient cleavage.
      Mutation of an additional six residues located upstream and downstream of this
      segment affects substrate hydrolysis as well. Vice versa, a readily cleavable TI
      VAMP molecule requires at the least the replacement of Ile158, Thr161, and the
      section 165-174 by Asp64, Ala67, and the 71-80 segment of VAMP-2, respectively.
      However, the insensitivity of TI-VAMP to botulinum neurotoxin B relies on at
      least 12 amino acid changes versus VAMP-2. These are scattered along an interface
      of 22 amino acid residues in length.

PMID- 16430922
TI  - Impulse control disorders in adults with obsessive compulsive disorder.
AB  - Little is known about impulse control disorders (ICDs) in individuals with
      obsessive compulsive disorder (OCD). Although studies have examined ICD
      comorbidity in OCD, no previous studies have examined clinical correlates of ICD
      comorbidity in a large sample of individuals with a primary diagnosis of OCD. We
      examined rates and clinical correlates of comorbid ICDs in 293 consecutive
      subjects with lifetime DSM-IV OCD (56.8% females; mean age=40.6+/-12.9 years).
      Comorbidity data were obtained with the Structured Clinical Interview for DSM-IV.
      ICDs were diagnosed with structured clinical interviews using DSM-IV criteria.
      OCD severity was assessed with the Yale-Brown Obsessive-Compulsive Scale. Quality
      of life and social/occupational functioning were examined using the Quality of
      Life Enjoyment and Satisfaction Questionnaire and the Social and Occupational
      Functioning Assessment Scale. All variables were compared in OCD subjects with
      and without lifetime and current ICDs. Forty-eight (16.4%) OCD subjects had a
      lifetime ICD, and 34 (11.6%) had a current ICD. Skin picking was the most common
      lifetime (10.4%) and current (7.8%) ICD, followed by nail biting with lifetime
      and current rates of 4.8% and 2.4%, respectively. OCD subjects with current ICDs
      had significantly worse OCD symptoms and poorer functioning and quality of life.
      These preliminary results suggest that there is a low prevalence of ICDs among
      individuals with OCD, although certain ICDs (skin picking) appear to be more
      common.

PMID- 16430923
TI  - Brain calcifications induce neurological dysfunction that can be reversed by a
      bone drug.
AB  - Perivascular calcifications within the brain form in response to a variety of
      insults. While considered by many to be benign, these calcium phosphate deposits
      or "brain stones" can become large and are associated with neurological symptoms
      that range from seizures to parkinsonian symptoms. Here we hypothesize that the
      high concentrations of calcium in these deposits produce reversible, toxic
      effects on neurons that can be overcome with "bone" drugs that chelate solid
      phase calcium phosphates. We present preliminary findings that suggest a direct
      association between progressive neurological symptoms and brain calcification and
      the symptomatic improvement of seizures, headaches, and parkinsonian symptoms in
      patients treated with the bisphosphonate drug disodium etidronate, normally used
      to treat bone diseases. Future, longitudinal epidemiological studies and
      randomized trials will be needed to determine the true relationship between brain
      stones and neurological disorders as well as the utility of bisphosphonates in
      their prevention and treatment.

PMID- 16430924
TI  - Possible multiple origins of replication in primate mitochondria: Alternative
      role of tRNA sequences.
AB  - DNA replication in vertebrate mitochondria is usually directional, leaving
      different portions of the genome single-stranded for different periods of time.
      During this time, mutations resulting from deaminations of cytosines to thymines
      and adenines to guanines accumulate on the heavy strand. Therefore, T/C and G/A
      ratios increase along mitochondrial genomes, proportionally to the time spent
      single-stranded during replication. Such trends exist at third codon positions
      for base ratios averaged across genes in individual genomes as well as for gene
      specific and site-specific substitution frequencies estimated using phylogenetic
      methods. We use multiple regressions to test for the potential functioning of all
      12 tRNA clusters in 19 primate mitochondrial genomes as alternative origins of
      light strand replication (OL). We provide a general algorithm for calculating
      time spent single stranded by a given site for any possible locations of the site
      and OL. For codon positions 1, 2, and 3, respectively, 23%, 9% and 35% of tRNA
      gene clusters have significant (p < 0.05) deamination gradients originating from
      them. The strength of the deamination gradient originating from tRNA gene
      clusters varies among species, and for five clusters, correlates with the
      tendency of tRNA genes in each of these clusters to form secondary structures
      that resemble the OL's structure. This is notably true for all codon positions
      for tRNA-Lys, which in absence of nuclear regulation, forms secondary structures
      resembling the hairpin structure of OL. For two tRNA gene clusters, correlations
      were statistically significant, but opposite to the direction expected by the
      known unidirectional replication, putatively compatible with bi-directional
      replication. Few substitutions in tRNA sequences can be neutral at the level of
      cloverleaf structure and function, yet significantly alter capacities to form OL
      like structures, causing sudden evolution of genome-wide nucleotide contents.

PMID- 16430925
TI  - Analysis of resonance chemotherapy in leukemia treatment via multi-staged
      population balance models.
AB  - An age-structured population balance model that explicitly models cell cycle
      phases is developed to investigate the effects of cell cycle specific (CCS)
      drugs. In particular, the benefits of timing CCS drug treatments in resonance
      chemotherapy are predicted and measured directly in vitro before evaluating
      likely in vivo scenarios. The phase transition rates are measured in vitro for
      the HL60 leukemia cell line and are used to predict the transient phase dynamics
      after exposure to the S phase specific drug, camptothecin. The phase oscillations
      predicted by the model are observed experimentally and the timing of a second
      camptothecin pulse is shown to significantly alter the overall treatment
      effectiveness. To explore the feasibility of designing resonance chemotherapeutic
      treatments to preferentially eliminate one cell type over another, Jurkat and
      HL60 leukemia cells are exposed to the same dual-pulse camptothecin treatment
      regimen. With the model framework validated for simplified cases, the model is
      used to extrapolate the effectiveness of resonance chemotherapy considering in
      vivo effects such as quiescence, drug metabolism, drug properties, and transport
      considerations that were not included in the in vitro experiments. While
      resonance chemotherapy is intuitive and looks promising in vitro, when in vivo
      considerations are included in the model, the phenomenon is dampened and the
      window of applicability becomes narrower.

PMID- 16430926
TI  - Brief heat shock affects the permeability and thermotolerance of an in vitro
      blood-brain barrier model of porcine brain microvascular endothelial cells.
AB  - Heat shock was imposed on an in vitro model of the blood-brain barrier (BBB) by
      submersion into prewarmed growth medium. Transendothelial electrical resistance
      (TEER) was used to assess the functional integrity of the endothelial barrier.
      Consequences of the heat shock were highly dependent upon the temperature and
      duration of exposure. Temperatures below 47 degrees C required more than 30 s of
      exposure to significantly impair barrier function, but full recovery occurred
      within 1 h. When the temperature was 50-54 degrees C, an exposure of only 10 s
      significantly diminished barrier function. Ten seconds of 51 degrees C or 54
      degrees C caused a significant loss of barrier function (45% and 80%,
      respectively). Full recovery from the 51 degrees C shock occurred within 5 min,
      while recovery from the 54 degrees C shock required more than 10 h. When the
      temperature was 57 degrees C or greater, a 3-s duration diminished barrier
      function by 80%. In response to heat shock, the brain microvascular endothelial
      cells developed thermotolerance and over-compensated in their ability to form a
      physiological barrier. The BBB models lost more than 60% of barrier function when
      initially exposed to 53 degrees C for 5 s but lost only 30% of function when
      exposed to the same treatment 24 h later. The BBB models over-compensated to
      produce a reinforced barrier with double the original TEER following repeated
      application of heat treatment (57 degrees C for 3 s). In vivo experiments will
      require exquisite manipulation of the temperature and duration in order to
      achieve the desired opening of the BBB in therapeutic applications.

PMID- 16430928
TI  - Characterization of proteinase-activated receptor 2 signalling and expression in
      rat hippocampal neurons and astrocytes.
AB  - Proteinase-activated receptors (PARs1-4) have recently been identified as the
      molecular entity underlying the cellular effects of serine proteinases. In the
      present study we have investigated PAR2 signalling, expression and
      desensitization using cultured and acute slice preparations. Trypsin, SLIGRL and
      2f-LIGKV-OH, agonists for PAR2, induced a transient increase in intracellular
      Ca(2+) levels in both neurons and astrocytes, via activation of the phospholipase
      C/IP(3) pathway. Furthermore, a single application of trypsin, but not SLIGRL nor
      2f-LIGKV-OH, leads to prolonged desensitization of PAR2 responses. PAR2
      immunoreactivity was observed in neurons (glutamatergic and GABAergic) and
      astrocytes within cultures and acute slices, with prominent labelling in neuronal
      somata and proximal dendrites. Functionally, cultured neurons which exhibited the
      highest levels of PAR2 labelling, also exhibited the largest Ca(2+) signals upon
      PAR2 activation. Given the importance of Ca(2+) signalling in hippocampal
      synaptic plasticity and neurodegeneration, PAR2 may play a key modulatory role in
      these processes.

PMID- 16430927
TI  - The in vivo properties of pagoclone in rat are most likely mediated by 5'-hydroxy
      pagoclone.
AB  - The cyclopyrrolone pagoclone binds with roughly equivalent high affinity (0.7
      9.1nM) to the benzodiazepine binding site of human recombinant GABA(A) receptors
      containing either an alpha1, alpha2, alpha3 or alpha5 subunit. However, whereas
      it was a partial agonist at alpha1-, alpha2- and alpha5-containing GABA(A)
      receptors, pagoclone was a full agonist at receptors containing an alpha3
      subunit. In the rat elevated plus maze assay pagoclone (3mg/kg) had significant
      anxiolytic-like activity but at all three doses tested (0.3, 1 and 3mg/kg p.o.)
      it produced a significant reduction in the total distance travelled. This
      sedative-like effect was confirmed in rat chain-pulling and spontaneous locomotor
      assays. Surprisingly, in the plasma and brain samples derived from the elevated
      plus maze assay, the major metabolite of pagoclone, 5'-hydroxy pagoclone, was
      present at 10-20-fold higher concentrations relative to the parent compound. In
      order to establish whether this metabolite might have pharmacological activity,
      we measured its affinity and efficacy profile and found that both were comparable
      to those of pagoclone with the exception that efficacy at the alpha1 subtype was
      considerably greater for 5'-hydroxy pagoclone compared with the parent. This
      metabolite had significant anxiolytic-like activity in the elevated plus maze but
      at these same doses (0.3-3mg/kg p.o.) also produced sedation. It is therefore
      likely that in rats 5'-hydroxy pagoclone mediates the majority of the
      pharmacological actions following pagoclone administration.

PMID- 16430929
TI  - Metallothionein expression and neurocognitive function in mice.
AB  - Transition metals have been associated with impaired neurological development,
      and neurobehavioral activity. Metallothioneins are central components in the
      metabolism and detoxification of a variety of metals, however, little is known
      concerning their role in cognitive function. To determine the role of
      metallothionein in learning and memory, mice with deletions of two
      metallothionein genes (MT-1 and MT-2) were trained on a win-shift task in an 8
      arm radial maze. The parental strain of mice learned the maze at a normal rate
      over an 18-session acquisition period. In contrast, the MT-1/MT-2-null mice,
      which had a similar choice accuracy level at the beginning of training, showed a
      poorer rate of learning during the training period. In addition, the MT-1/MT-2
      null mice showed significantly less choice accuracy than the parental strain. The
      MT-1/MT-2-null mice also showed a significant hypoactivity during the early and
      middle parts of acquisition training, but they were not different from the
      wildtype controls during the final phase of training. Nicotine treatment, which
      can improve working memory, eliminated the impairment associated with the
      deletion of the MT-1 and MT-2 genes in a dose-related fashion after acquisition
      training in the aging adult mice. These results suggest that metallothioneins,
      through there roles in metal physiology or cellular protection, are involved in
      spatial learning and memory function.

PMID- 16430930
TI  - Human interaction and cortisol: can human contact reduce stress for shelter dogs?
AB  - Animal shelters are an extremely stressful environment for a dog, most
      specifically due to social isolation and novel surroundings. The stress response
      of dogs housed in this environment may be alleviated through human interaction
      shortly after arrival. During their second day in a public animal shelter, adult
      stray dogs were either engaged in a human contact session or not. The session
      involved taking the dog into an outdoor enclosure, playing with the dog,
      grooming, petting and reviewing basic obedience commands. Each dog interacted
      with a human for approximately 45 min. Salivary cortisol levels were examined
      from each dog on their 2nd, 3rd, 4th and 9th day of housing. Animals that engaged
      in a human contact session had lower cortisol levels on day 3 than animals that
      did not. Breed type, sex and age did not have an effect on cortisol levels on any
      day measured. A human interaction session can be beneficial to both animal
      welfare and adoption procedures. The current study not only utilized the human
      contact session as a treatment to reduce stress but also as a resource for
      individual temperament/personality information that could be later used to
      facilitate compatible adoptions. Human interaction may be an effective means of
      reducing the cortisol response of dogs in the aversive shelter environment.

PMID- 16430931
TI  - Nep1-like proteins from plant pathogens: recruitment and diversification of the
      NPP1 domain across taxa.
AB  - An emerging group of proteins found in many plant pathogens are related to their
      ability to cause plant cell death. These proteins may be identified by the
      presence of a common NPP1 (necrosis-inducing Phytophthora protein) domain, and
      have collectively been named NLPs (Nep1-like proteins). The NLPs are
      distinguished by their wide distribution across taxa and their broad spectrum of
      activity against dicotyledonous plants. The function of NLPs is not known but
      there is strong evidence that they may act as positive virulence factors,
      accelerating disease and pathogen growth in plant hosts. Interest in NLPs is
      gaining momentum as more members of this protein family are discovered in more
      species of plant pathogens.

PMID- 16430932
TI  - C-prolinylquercetins from the yellow cocoon shell of the silkworm, Bombyx mori.
AB  - Two flavonoids containing the l-proline moiety, 6-C-[(2S,5S)-prolin-5-yl]
      quercetin (prolinalin A) and 6-C-[(2S,5R)-prolin-5-yl] quercetin (prolinalin B),
      were isolated from the cocoon shell of the silkworm, Bombyx mori. Their
      structural elucidation was achieved by application of acid hydrolysis and
      spectroscopic methods. These compounds were not found in the leaves of mulberry
      (Morus alba L.), the host plant of the silkworm, suggesting that the flavonoids
      are metabolites of the insect. This is the first time that flavonoids with an
      amino acid moiety have been found as naturally occurring compounds.

PMID- 16430933
TI  - Gender, equity: new approaches for effective management of communicable diseases.
AB  - This editorial article examines what is meant by sex, gender and equity and
      argues that these are critical concepts to address in the effective management of
      communicable disease. Drawing on examples from the three major diseases of
      poverty (HIV, tuberculosis [TB] and malaria), the article explores how, for women
      and men, gender and poverty can lead to differences in vulnerability to illness;
      access to quality preventive and curative measures; and experience of the impact
      of ill health. This exploration sets the context for the three companion papers
      which outline how gender and poverty shape responses to the three key diseases of
      poverty in different geographical settings: HIV/AIDS in Kenya; TB in India; and
      malaria in Ghana.

PMID- 16430934
TI  - Adequacy of saliva 17-hydroxyprogesterone determination using various collection
      methods.
AB  - Steroids determination in saliva offers several advantages. The collection of
      saliva is a noninvasive, less stressful technique than blood withdrawal and
      reflects the circulating unbound fractions. The suitability of saliva for 17
      hydroxyprogesterone and cortisol determinations has been documented in healthy
      subjects as well as in diseases like Congenital Adrenal Hyperplasia and Cushing
      syndrome. The aim of the study was to compare the influence of different
      collection methods on the results of 17-hydroxyprogesterone measurement in saliva
      collected by different ways, using commercially available RIAs developed for
      plasma. 17-hydroxyprogesterone was determined in 64 healthy adult volunteers (30
      males, 34 females) in serum (Group SE) and in saliva collected before meals at 8
      10 p.m. by directly spitting into a plastic tube (Group SP), using a cotton swab
      (Group SA) and using a polyester swab Salivette (Group SB). We used a
      commercially available direct radioimmunoassay without separation technique. The
      17-hydroxyprogesterone mean values (ng/ml) were 1.16+/-1.3 (Group SE), 0.056+/
      0.046 (Group SP), 0.089+/-0.048 (Group SA) and 0.058+/-0.049 (Group SB). The
      detection limit was 0.010 ng/ml. The correlations between the values in serum
      (Group SE) and in saliva were: r=0.77, p<0.05 (Group SP); r=0.62, p<0.05 (Group
      SA); r=0.70, p<0.05 (Group SB). The saliva values corresponding to the serum cut
      off point of 3 ng/ml upper limit of normal values were in ng/ml 0.13 (Group SP),
      0.16 (Group SA) and 0.11 (Group SB). In conclusion, 17-hydroxyprogesterone
      determinations in saliva using commercially available RIAs primarily developed
      for serum, is a reliable and easy to perform procedure. The three different
      methods of saliva collection showed 17-hydroxyprogesterone concentrations to have
      good agreement.

PMID- 16430935
TI  - Enhancement of DMNQ-induced hepatocyte toxicity by cytochrome P450 inhibition.
AB  - Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative
      stress via the redox cycle and the arylation of intracellular nucleophiles. As
      the redox cycle is catalyzed by NADPH cytochrome P450 reductase, cytochrome P450
      systems are expected to be related to the cytotoxicity induced by redox-cycling
      quinones. Thus, we investigated the relationship between cytochrome P450 systems
      and quinone toxicity for rat primary hepatocytes using an arylator, 1,4
      benzoquinone (BQ), and a redox cycler, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ).
      The hepatocyte toxicity of both BQ and DMNQ increased in a time- and dose
      dependent manner. Pretreatment with cytochrome P450 inhibitors, such as SKF-525A
      (SKF), ketoconazole and 2-methy-1,2-di-3-pyridyl-1-propanone, enhanced the
      hepatocyte toxicity induced by DMNQ but did not affect BQ-induced hepatocyte
      toxicity. The production of superoxide anion and the levels of glutathione
      disulfide and thiobarbituric-acid-reactive substances were increased by treatment
      with DMNQ, and SKF pretreatment further enhanced their increases. In addition,
      NADPH oxidation in microsomes was increased by treatment with DMNQ and further
      augmented by pretreatment with SKF, and a NADPH cytochrome P450 reductase
      inhibitor, diphenyleneiodonium chloride completely suppressed NADPH oxidations
      increased by treatment with either DMNQ- or DMNQ + SKF. Pretreatment with
      antioxidants, such as alpha-tocopherol, reduced glutathione, N-acetyl cysteine or
      an iron ion chelator deferoxamine, totally suppressed DMNQ- and DMNQ + SKF
      induced hepatocyte toxicity. These results indicate that the hepatocyte toxicity
      of redox-cycling quinones is enhanced under cytochrome P450 inhibition, and that
      this enhancement is caused by the potentiation of oxidative stress.

PMID- 16430936
TI  - Possible mechanism for species difference on the toxicity of pivalic acid between
      dogs and rats.
AB  - In a high dose toxicity study of pivalic acid (PA), PA caused skeletal muscle
      disorder in dog, and a significant increase of pivaloyl carnitine (PC) was
      observed in canine muscle, but not in rat muscle. In order to understand species
      difference of the toxicity of PA, we compared the in vitro metabolism of PA among
      dog, rat and rabbit, especially focussing on the carnitine conjugate. Canine
      muscle showed low, but significant carnitine conjugating activity, while that of
      rat was negligible. Canine kidney mitochondria had significant activity in the
      pivaloyl CoA synthesis (7 nmol/mg protein/h), but muscle mitochondria showed only
      trace activity. Both kidney and muscle mitochondria displayed similar carnitine
      acyltransferase activity (2-3 nmol/mg protein/h) towards pivaloyl CoA. On the
      other hand, with respect to the activity of carnitine acyltransferase in the
      reverse direction using PC as substrate, canine muscle mitochondria showed higher
      activity than that of kidney mitochondria. This means that PC is not the final
      stable metabolite, but is converted easily to pivaloyl CoA in canine muscle.
      These results suggest one of the possible mechanisms for canine selective muscle
      disorder to be as follows. Only canine muscle can metabolize PA to its carnitine
      conjugate slowly, but significantly. In canine muscle, PC is not the final stable
      metabolite; it is easily converted to pivaloyl CoA. As carnitine conjugation is
      thought to be the only detoxification metabolic route in canine muscle, under
      certain circumstances such as carnitine deficiency, the risk of exposure with
      toxic pivaloyl CoA might increase and the CoASH pool in canine muscle might be
      exhausted, resulting in toxicity in canine muscle.

PMID- 16430937
TI  - Reflection and transmission at normal incidence onto air-saturated porous
      materials and direct measurements based on parametric demodulated ultrasonic
      waves.
AB  - The present work is related to the characterization of air-saturated porous media
      by using parametric demodulated ultrasonic waves. One uses two different powerful
      ultrasonic emitters working either at 47 kHz or at 162 kHz which are
      electronically amplitude modulated over the 200 Hz-4 kHz or 2 kHz-40 kHz
      bandwidths respectively. The demodulation process takes place in air, due to its
      nonlinearity enabling to generate audio range acoustical waves or alternatively
      low frequency ultrasonic waves which can be used to characterize porous materials
      in the reflection configuration at normal incidence. Some appropriate theoretical
      calculations are introduced for three configurations of interest, i.e. a porous
      slab, a porous layer mounted onto a rigid plate, and a porous half space, in the
      case of the equivalent-fluid model. Comparisons between theoretical modeling and
      experimental data are provided and prospective industrial applications are
      discussed.

PMID- 16430938
TI  - Transgenic reporter mouse for bioluminescence imaging of herpes simplex virus 1
      infection in living mice.
AB  - Bioluminescence imaging allows spatial and temporal progression of viral
      infection to be detected and quantified in living mice, thereby providing a new
      approach for studies of viral-host pathogenesis. It has been necessary to
      construct and validate recombinant reporter viruses that express firefly
      luciferase to investigate viral replication and spread with this imaging
      technology. This strategy greatly limits the ability to analyze multiple strains
      of virus and/or existing viral mutants, and reporter viruses also may be
      attenuated relative to the respective parental viruses. To facilitate
      bioluminescence imaging of herpes simplex virus type 1 (HSV-1), we developed a
      transgenic reporter mouse that uses the promoter from HSV-1 thymidine kinase to
      control expression of firefly luciferase. Infection with HSV-1 activated
      expression of firefly luciferase in corneal and flank models of infection, and
      amounts of bioluminescence increased in proportion to increasing input titers of
      virus. Imaging could detect infection with three different strains of HSV-1 with
      the following relative rank order of bioluminescence produced at the site of
      infection: McKrae > 17 > KOS. Corneal infection with as few as 1 x 10(3) pfu
      strain McKrae was detectable above background levels. By comparison, infection
      with vaccinia virus did not affect bioluminescence in the reporter mouse.
      Collectively, these data establish a new transgenic reporter mouse for infection
      with HSV-1, thereby enabling in vivo bioluminescence imaging studies of HSV-1
      pathogenesis without constructing new reporter viruses.

PMID- 16430940
TI  - Betanodavirus induces phosphatidylserine exposure and loss of mitochondrial
      membrane potential in secondary necrotic cells, both of which are blocked by
      bongkrekic acid.
AB  - In this study, we show how the red spotted grouper nervous necrosis virus (RGNNV)
      causes loss of mitochondrial membrane potential and promotes host secondary
      apoptotic necrosis. RGNNV viral proteins such as protein alpha (42 kDa) and
      protein A (110 kDa) were quickly expressed between 12 h and 24 h postinfection
      (p.i.) in GL-av cells. Annexin V staining revealed that the NNV infection of GL
      av cells induced phosphatidylserine (PS) externalization and development of bulb
      like vesicles (bleb formation) at 24 h p.i. NNV infection also induced DNA
      fragmentation detectable by TUNEL assay between 12 h (8%) and 72 h (32%) p.i.
      Bongkrekic acid (1.6 microM; BKA) blocked permeability of the mitochondrial
      permeability transition pore, but cyclosporine A (CsA) did not block secondary
      necrosis. Finally, secondary necrotic cells were not engulfed by neighboring
      cells. Our data suggest that RGNNV induces apoptotic death via opening the
      mitochondrial permeability transition pore thereby triggering secondary necrosis
      in the mid-apoptotic phase.

PMID- 16430939
TI  - Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate.
AB  - The selective pressure of the competitive protease inhibitors causes both HIV-1
      protease and occasionally its substrates to evolve drug resistance. We
      hypothesize that this occurs particularly in substrates that protrude beyond the
      substrate envelope and contact residues that mutate in response to a particular
      protease inhibitor. To validate this hypothesis, we analyzed substrate and
      protease sequences for covariation. Using the chi2 test, we show a positive
      correlation between the nelfinavir-resistant D30N/N88D protease mutations and
      mutations at the p1-p6 cleavage site as compared to the other cleavage sites.
      Both nelfinavir and the substrate p1-p6 protrude beyond the substrate envelope
      and contact residue 30, thus possibly making the p1-p6 cleavage site more
      vulnerable to co-evolution.

PMID- 16430941
TI  - Functional gene analysis of individual response to challenge of SIVmac239 in M.
      mulatta PBMC culture.
AB  - It has previously been shown in macaques that individual animals exhibit varying
      responses to challenge with the same strain of SIV. We attempted to elucidate
      these differences using functional genomics and correlate them to biological
      response. Unfractionated PBMC from three rhesus macaques were isolated,
      activated, and infected with SIVmac239. Interestingly, one of the three animals
      used for these experiments exhibited a completely unique response to infection
      relative to the other two. After repeated attempts to infect the PBMC from this
      animal, little or no infectivity was seen across the time points considered, and
      corresponding to this apparent lack of infection, few genes were seen to be
      differentially expressed when compared to mock-infected cells. For the remaining
      two animals, gene expression analysis showed that while they exhibited responses
      for the same groups of pathways, these responses included differences specific to
      the individual animal at the gene level. In instances where the patterns of
      differential gene expression differed between these animals, the genes being
      differentially expressed were associated with the same categories of biological
      process, mainly immune response and cell signaling. At the pathway level, these
      animals again exhibited similar responses that could be predicted based on the
      experimental conditions. Even in these expected results, the degree of response
      and the specific genes being regulated differed greatly from animal to animal.
      The differences in gene expression on an individual level have the potential to
      be used as markers in identification of animals suitable for lentiviral infection
      experiments. Our results highlight the importance of individual variation in
      response to viral challenge.

PMID- 16430942
TI  - Attentional capacity limit for visual search causes spatial neglect in normal
      observers.
AB  - When observers simultaneously monitor several positions in the visual field,
      distracting stimuli have a devastating effect on the ability to discriminate
      between similar shapes. For example, the minimum tilt necessary for an observer
      to discriminate between a clockwise and anticlockwise tilt has been shown to
      increase with the square root of the number of untilted distractors. Here we show
      that these rapid visual searches remain inefficient even with extended practice.
      Moreover, each of our observers performed particularly poorly when uncued targets
      appeared in certain idiosyncratic positions, as though he or she neglected to
      process part of the visual field. This type of neglect is not commensurate with
      the popular 'max rule' strategy, in which observers simply report the direction
      of the largest apparent tilt. Nor is it consistent with tilt averaging. It is,
      however, consistent with an attentional effect in which both the signal and the
      noise from neglected positions are decreased, leaving the local signal/noise
      ratio constant. We show that our data can be well fit by models in which
      discriminations are based on a combination of these locally weighted, noisy
      signals.

PMID- 16430943
TI  - Mitochondrial membrane damage during aging process in rat heart: potential
      efficacy of L-carnitine and DL alpha lipoic acid.
AB  - Mitochondria are the main intracellular source of oxidizing free radicals and
      these oxidants produced exhibit selectivity in damaging mitochondrial
      macromolecules and membrane functions. In the present study we have investigated
      the effect of co-supplementation of carnitine (300 mg/kg bw) and lipoic acid (100
      mg/kg bw) for 28 days in young, middle aged and aged rats and evaluated the
      effect of these compounds on age-related alterations in mitochondrial membrane
      functions. The levels of H2O2 were increased in both middle aged and aged rats
      with a concomitant decrease in the levels of cardiolipin and mitochondrial
      membrane potential. The levels of membrane bound ATPases were also decreased in
      aged rats along with alterations in mitochondrial morphology. Supplementation of
      carnitine and lipoic acid to middle aged and aged rats brought these changes to
      near normalcy. Thus, lipoic acid acts with carnitine to improve mitochondrial
      supported bioenergetics and also improves general antioxidant status, thereby
      effectively attenuating any putative increase in oxidative stress with age.

PMID- 16430944
TI  - Novel, semi-automated, 60-min-assay to determine von Willebrand factor cleaving
      activity of ADAMTS-13.
AB  - INTRODUCTION: The clinical entity of idiopathic thrombotic thrombocytopenic
      purpura (TTP) has been closely associated with a severe deficiency of the von
      Willebrand factor (vWF)-cleaving protease (ADAMTS-13). Levels below 5% are highly
      specific for TTP basically excluding hemolytic uremic syndrome (HUS). Deficiency
      of ADAMTS-13 can either be inherited or caused by inhibitory IgG autoantibodies
      to ADAMTS-13. Diagnosis of TTP is often difficult since it often manifests
      oligosymptomatic exhibiting only laboratory signs of thrombocytopenia and
      hemolysis or involving atypical organs. In such cases rapid knowledge of the
      ADAMTS-13 activity is very useful in helping to establish a correct diagnosis
      rapidly and to initiate the appropriate therapy. METHODS AND RESULTS: We have
      therefore designed a rapid, sensitive and simple assay for the determination of
      ADAMTS-13 activity and ADAMTS-13 inhibitors. The test is based on the measurement
      of the ristocetin-cofactor activity of purified, urea-denaturated vWF concentrate
      after incubation with diluted patient plasma that has been preactivated with
      barium chloride. While this assay has already previously been established, we
      have further modified and simplified the test thereby improving markedly the
      sensitivity, accuracy and turn-around time. A major improvement proved to be the
      change from buffer to heat-treated and vWF-replenished plasma as diluent for
      making the serial dilutions of normal pool plasma (NPP) for the calibration
      curve. Set up as a semi-automated assay the test is performed in only 50 to 60
      min. Tested in 15 patients with ADAMTS-13 deficiency this new assay compared
      favorably and even more accurately with the classic electrophoretic ADAMTS-13
      assay, especially in the low range below 10%. Mixing studies with patient plasma
      and NPP (ratio 1:1) revealed that a relatively short period of only 30 min at
      room temperature is sufficient for most samples to detect an inhibitor. With a
      single mixing experiment it is possible to discriminate inhibitor levels in the
      range of 0.5-4 Bethesda units. CONCLUSION: Using this novel assay, determination
      of ADAMTS-13 activity and ADAMTS-13 inhibitors can be performed easily, rapidly
      (less than 2 h), and accurately, providing rapid information about the severity
      of ADAMTS-13 deficiency and the presence of an inhibitor. In addition, the test
      is suitable for full automation enabling to screen large populations and, thus,
      help to get further insights into the clinical significance of ADAMTS-13
      deficiency in other diseases.

PMID- 16430945
TI  - Immunohistochemical assessment of fibronectin and tenascin and their integrin
      receptors alpha5beta1 and alpha9beta1 in gastric and colorectal cancers with
      lymph node and liver metastases.
AB  - The aim of the current study was to assess immunohistochemically and compare the
      level of expression of tenascin (TN) and fibronectin (FN) and their integrin
      receptors alpha9beta1 and alpha5beta1 in the primary colorectal and gastric
      tumors, and in corresponding lymph node and liver metastases from 53 patients. We
      detected similar high deposition of the studied ECM proteins and their receptors
      in the stroma of primary tumors and in liver metastases and a lower deposition in
      lymph node metastases. Cytoplasmic immune reaction for FN and TN was also seen in
      the tumor cells. A pronounced co-localization of immune deposits for FN and TN
      and their receptors was found in the stroma of the center and the invasion front
      (IF) (p<0.0001). A significant decrease of FN immune signal was observed in the
      IF in primary tumors and liver metastases (p<0.0001). The levels of
      immunolabeling of FN and TN correlated with the differentiation grade of primary
      tumors (p<0.0001). In conclusion, we may say that there is heterogeneous
      deposition of TN, FN and their integrin receptors in the different areas of
      primary colorectal and gastric tumors and of their metastases. These findings
      imply that the studied proteins may be involved in cell processes such as growth,
      adhesion, migration and apoptosis.

PMID- 16430946
TI  - The significance of cytological mesothelial atypia diagnosed from peritoneal
      washings performed during risk-reducing salpingo-oophorectomy.
AB  - OBJECTIVE: Occult cancer may be found in a small proportion of women undergoing
      risk-reducing salpingo-oophorectomy (RRSO). However, the results and significance
      of peritoneal wash cytology in this setting are not clear. The objective of this
      study was to determine the significance of cytologic mesothelial atypia in the
      peritoneal washings of patients undergoing RRSO. METHODS: We conducted a
      retrospective chart review of all patients undergoing RRSO from July 2002 to
      December 2003. Patient charts were reviewed for information regarding cytology,
      pathology, demographics, surgical procedure and findings, and outcome. RESULTS:
      One hundred thirty women underwent RRSO during the study period. One hundred
      seventeen had washings performed during the procedure and constitute the study
      cohort. The median age at the time of the procedure was 48 years (range, 33-78
      years). Final cytology was reported as normal in 102 patients (87%), mesothelial
      atypia in 13 (11%), and non-satisfactory in 2 (2%). Ovarian and tubal
      histopathology was normal in all cases. No association was found between
      mesothelial atypia and age, prior breast cancer, or prior abdominal surgery.
      Twenty-nine patients had previously undergone genetic testing for BRCA1/2
      mutations as part of ongoing prospective follow-up studies. Four (24%) of 17
      patients with a known BRCA1 or BRCA2 mutation were found to have mesothelial
      atypia compared to 1 (8%) of 12 with no mutation. With a median follow-up time of
      20 months (range, 1-40 months), none of the patients with mesothelial atypia were
      diagnosed with peritoneal malignancy following RRSO. CONCLUSION: In this study,
      mesothelial atypia was identified in 11% of patients who had peritoneal washings
      performed at the time of RRSO. No patients with mesothelial atypia went on to
      develop peritoneal carcinoma. The link between mesothelial atypia and mutations
      in BRCA1/2 and the need to perform peritoneal washings in this setting are both
      yet to be determined.

PMID- 16430947
TI  - Adenocarcinoma of the uterine cervix with choriocarcinomatous metastasis.
AB  - BACKGROUND: Nongestational choriocarcinoma, in very rare instances, has been
      described as a component of other malignancies with a tendency for a very poor
      prognosis. CASE: A 55 year old woman was diagnosed with adenocarcinoma of the
      cervix, and incompletely treated with only external beam radiation. Adjuvant
      radical hysterectomy demonstrated no residual tumor, but the patient developed a
      tumor metastasis mimicking a pulmonary artery thrombus which by histology and
      immunohistochemistry was pure choriocarcinoma. While chemotherapy was successful
      in achieving a complete remission, the patient succumbed to complications of her
      pulmonary metastasis. CONCLUSION: Choriocarcinomatous dedifferentiation of
      cervical adenocarcinoma is extremely rare, with only one other case reported in
      the literature. While the prognosis for patients with such a tumor is generally
      poor, aggressive combination chemotherapy may be of benefit in some.

PMID- 16430948
TI  - Nicotine-ethanol interactions in flash-evoked potentials and behavior of Long
      Evans rats.
AB  - Although nicotine and ethanol are often used together, little is known about
      their combined effects on visual system electrophysiology. This experiment
      examined the separate and combined effects of nicotine and ethanol on flash
      evoked potentials (FEPs) recorded from both the visual cortex (VC) and superior
      colliculus (SC) of chronically implanted male Long-Evans rats. There were four
      treatment conditions administered on separate days: either saline or ethanol (2.0
      g/kg, i.p.) was given 10 min before either saline or nicotine (1.0 mg/kg, s.c.).
      FEPs were recorded at 5, 20, and 40 min following the second injection. In the
      VC, ethanol significantly decreased the amplitude of most components, but
      increased P46. Peaks P22 and N53 were unchanged. Nicotine enhanced most component
      amplitudes, but decreased N29 and P234, while P22 and N139 were unchanged. In the
      SC, ethanol depressed the amplitude of all components studied. In contrast,
      nicotine significantly depressed only P27 and N48. Latencies of most components
      in both structures were increased by ethanol, nicotine, and the combination
      treatment, although a nicotine-induced enhancement of the effects of ethanol on
      latencies was not typically observed. Each drug treatment also produced
      significant hypothermia, with the combination treatment resulting in the greatest
      hypothermia. Ethanol, either alone or in combination with nicotine, significantly
      reduced body movements during the FEP recording sessions. In subsequent open
      field observations, ethanol, but not nicotine, significantly increased the number
      of squares crossed, while the combination treatment produced the greatest
      increase in movement. Nicotine significantly increased rearing behavior, but both
      ethanol and the combination treatment eliminated rearings. Overall, data
      suggesting that nicotine can counteract some of the effects of ethanol was
      demonstrated in varying degrees in the amplitude of VC components N39, P46, N53,
      N65, and P88, the latency of VC component N53, the amplitude of SC component N59,
      and the latency of SC components N48 and N54. In contrast, a nicotine-induced
      enhancement of the effects of ethanol was found for only the latency of VC
      components N39, P88, and P234, body temperature, and open-field ambulation.

PMID- 16430949
TI  - Orthographic directionality and thematic role illustration in English and Arabic.
AB  - This study tested the hypotheses that people had a bias for drawing agents on the
      left of a picture when given a verb stimulus targeting an active or passive event
      (e.g., "kicked" or "is kicked") and that orthographic directionality would
      influence the way events were illustrated. Monolingual English speakers, who read
      and write left-to-right, and Arabic speakers, who read and write right-to-left,
      drew agents and patients in response to verb stimuli. We found no significant
      orthographic directionality effects and no preference for positioning agents on
      the left of pictures in either group or sentence type. Instead, participants drew
      agents on the right regardless of language or sentence type, and this was
      exaggerated in English speakers illustrating passive verbs. These findings
      support the existence of a preference for placing agents in the right hemispace
      that may result from asymmetrical hemispheric (i.e., left>right) activation
      induced by language processing. Our results are consistent with findings that
      people prefer pictures in which focus is on the right, a preference strongest in
      pictures with no implicit directionality of movement. This suggests that the
      methodology of the current study encouraged a static rather than dynamic
      interpretation of the verb in most participants.

PMID- 16430950
TI  - Asymmetries for the visual expression and perception of speech.
AB  - This study explored asymmetries for movement, expression and perception of visual
      speech. Sixteen dextral models were videoed as they articulated: 'bat,' 'cat,'
      'fat,' and 'sat.' Measurements revealed that the right side of the mouth was
      opened wider and for a longer period than the left. The asymmetry was accentuated
      at the beginning and ends of the vocalization and was attenuated for words where
      the lips did not articulate the first consonant. To measure asymmetries in
      expressivity, 20 dextral observers watched silent videos and reported what was
      said. The model's mouth was covered so that the left, right or both sides were
      visible. Fewer errors were made when the right mouth was visible compared to the
      left--suggesting that the right side is more visually expressive of speech.
      Investigation of asymmetries in perception using mirror-reversed clips revealed
      that participants did not preferentially attend to one side of the speaker's
      face. A correlational analysis revealed an association between movement and
      expressivity whereby a more motile right mouth led to stronger visual
      expressivity of the right mouth. The asymmetries are most likely driven by left
      hemisphere specialization for language, which causes a rightward motoric bias.

PMID- 16430951
TI  - Real-time PCR for prenatal and preimplantation genetic diagnosis of monogenic
      diseases.
AB  - The provision of prenatal diagnosis requires the highest standards in laboratory
      practice to ensure an accurate result. In preimplantation genetic diagnosis
      protocols additionally have to address the need to achieve an accurate result
      from 1 to 2 cells within a limited time. Emerging protocols of "non-invasive"
      prenatal diagnosis, which are based on analysis of free fetal DNA in the
      circulation of the pregnant mother, also have to achieve a result from a limited
      quantity of fetal DNA against a high background of maternal free DNA. Real-time
      PCR uses fluorescent probes or dyes and dedicated instruments to monitor the
      accumulation of amplicons produced throughout the progress of a PCR reaction.
      Real-time PCR can be used for quantitative or qualitative evaluation of PCR
      products and is ideally suited for analysis of nucleotide sequence variations
      (point mutations) and gene dosage changes (locus deletions or
      insertions/duplications) that cause human monogenic diseases. Real-time PCR
      offers a means for more rapid and potentially higher throughput assays, without
      compromising accuracy and has several advantages over end-point PCR analysis,
      including the elimination of post-PCR processing steps and a wide dynamic range
      of detection with a high degree of sensitivity. This review will focus on real
      time PCR protocols that are suitable for genotyping monogenic diseases with
      particular emphasis on applications to prenatal diagnosis, non-invasive prenatal
      diagnosis and preimplantation genetic diagnosis.

PMID- 16430952
TI  - Modeling the investment casting of a titanium crown.
AB  - OBJECTIVE: The objective of this study was to apply computational modeling tools
      to assist in the design of titanium dental castings. The tools developed should
      incorporate state-of-the-art micromodels to predict the depth to which the
      mechanical properties of the crown are affected by contamination from the mold.
      The model should also be validated by comparison of macro- and micro-defects
      found in a typical investment cast titanium tooth crown. METHODS: Crowns were
      hand-waxed and investment cast in commercial purity grade 1 (CP-1) titanium by a
      commercial dental laboratory. The castings were analyzed using X-ray
      microtomography (XMT). Following sectioning, analysis continued with optical and
      scanning electron microscopy, and microhardness testing. An in-house cellular
      automata solidification and finite-difference diffusion program was coupled with
      a commercial casting program to model the investment casting process. A three
      dimensional (3D) digital image generated by X-ray tomography was used to generate
      an accurate geometric representation of a molar crown casting. Previously
      reported work was significantly expanded upon by including transport of dissolved
      oxygen and impurity sources upon the arbitrarily shaped surface of the crown, and
      improved coupling of micro- and macro-scale simulations. RESULTS: Macroscale
      modeling was found to be sufficient to accurately predict the location of the
      large internal porosity. These are shrinkage pores located in the thick sections
      of the cusp. The model was used to determine the influence of sprue design on the
      size and location of these pores. Combining microscale with macroscale modeling
      allowed the microstructure and depth of contamination to be predicted
      qualitatively. This combined model predicted a surprising result--the dissolution
      of silicon from the mold into the molten titanium is sufficient to depress the
      freezing point of the liquid metal such that the crown solidifies the subsurface.
      Solidification then progresses inwards and back out to the surface through the
      silicon-enriched near-surface layer. The microstructure and compositional
      analysis of the near-surface region are consistent with this prediction.
      SIGNIFICANCE: A multiscale model was developed and validated, which can be used
      to design CP-Ti dental castings to minimize both macro- and micro-defects,
      including shrinkage porosity, grain size and the extent of surface contamination
      due to reaction with the mold material. The model predicted the surprising result
      that the extent of Si contamination from the mold was sufficient to suppress the
      liquidus temperature to the extent that the surface (to a depth of approximately
      100 microm) of the casting solidifies after the bulk. This significantly
      increases the oxygen pickup, thereby increasing the depth of formation of alpha
      casing. The trend towards mold materials with reduced Si in order to produce
      easier-to-finish titanium castings is a correct approach.

PMID- 16430953
TI  - Apoptosis induced by the monomers HEMA and TEGDMA involves formation of ROS and
      differential activation of the MAP-kinases p38, JNK and ERK.
AB  - OBJECTIVES: Cytotoxic methacrylate monomers have been identified in aqueous
      extracts of freshly cured compomers. Some of these compounds, including HEMA and
      TEGDMA, induce apoptosis and necrosis in vitro. The aim of the present study was
      to elucidate possible signaling pathways involved in apoptosis following exposure
      to HEMA or TEGDMA in a salivary gland cell line. METHODS: The cells were exposed
      to various concentrations of HEMA or TEGDMA. ROS formation was determined by
      dichlorofluorescein assay. Phosphorylated MAP-kinases ERK1/2, p38 and JNK, as
      well as specific caspases were identified by Western blotting. Apoptosis was
      assayed by fluorescence microscopy. RESULTS: HEMA or TEGDMA exposure resulted in
      ROS formation and concentration-dependent apoptosis as well as phosphorylation of
      ERK. Phosphorylation of JNK and p38 was induced by HEMA. Selective inhibitors of
      ERK and JNK modified the apoptotic response after HEMA and TEGDMA exposure,
      whereas p38 inhibition modified the apoptotic response only after HEMA exposure.
      Vitamin C reduced HEMA-induced apoptosis. SIGNIFICANCE: ROS formation and
      differential MAP kinase activation appear to be involved in the apoptotic
      response following exposure to HEMA and TEGDMA.

PMID- 16430955
TI  - Methyl methacrylate monomer-polymer equilibrium in solid polymer.
AB  - OBJECTIVE: Poly(methyl methacrylate) (PMMA) is commonly processed in dentistry by
      thermally initiating the free-radical polymerization of methyl methacrylate
      (MMA). Residual MMA, a tissue irritant, is a concern. The concentration of MMA
      ([MMA]) versus time and temperature was studied to identify optimum processing
      conditions. MATERIALS AND METHODS: One hundred milligram portions of plain and
      dental PMMA powders were incubated (10-170 degrees C, 1-384 h), with and without
      6.0 microL MMA added. After incubation, [MMA] was determined by GC. RESULTS: For
      plain PMMA alone, equilibrium was attained in about 100 h. The equilibrium data
      for log[MMA] versus 1/T was better fitted by a quadratic than a straight line,
      and formed an upper bound to the values of [MMA] when PMMA was incubated with MMA
      at temperatures > approximately 120 degrees C. The response surface for [MMA]
      versus log(time) and reciprocal temperature was fitted. An 'overshoot' in the
      equilibration process was identified, and postulated to be due to a rapidly
      formed intermediate of unknown chemistry. SIGNIFICANCE: Minimization of the
      residual MMA in acrylic denture bases prepared by processing a mixture of PMMA
      and MMA is important for reasons of mechanical properties and irritancy. The
      response surface mapped here allows direct identification of the optimum
      processing conditions.

PMID- 16430954
TI  - Polymerization efficacy of simplified adhesive systems studied by NMR and MRI
      techniques.
AB  - OBJECTIVE: To ascertain the efficacy of polymerization of self-etching dental
      adhesives in different solvent evaporation conditions. MATERIAL AND METHODS: Four
      self-etching adhesive systems were studied. Two of them are classified as mild
      two-step self-etching adhesives (Clearfil SE Bond, Protect Bond) and the other
      two are strong one-step systems (Xeno III, ADP-Prompt-L-Pop). The influence of
      temperature and duration of the air-drying period on photo-polymerization was
      followed by: gravimetry, (1)H solid-state NMR spectroscopy and stray-field MRI.
      The evolution of proton magnetization with irradiation time was recorded and
      correlated with volumetric polymerization shrinkage and extent of reaction;
      evaporation and hardening effects were identified. RESULTS: Main variables
      determining water-solvent evaporation of the tested adhesives are: (1) water/HEMA
      relative concentration, (2) presence of photoinitiator compounds in the primer
      (SEB) and (3) presence of ethanol (XENO). SEB shows the highest extent of photo
      polymerization of the tested adhesives. The lowest volumetric contraction was
      obtained for APLP and XENO and the attempt to remove the solvents did not
      increase the extent of polymerization significantly. CONCLUSIONS: Temperature
      increase following photo-polymerization reaction is dominant towards the effect
      of the drying step for solvent evaporation in self-etching systems. Attempts to
      remove the solvents did not increase the extent of polymerization, so other
      problems are impairing the polymerization of one-step adhesives. CLINICAL
      SIGNIFICANCE: The use of tested one-step adhesives is discouraged as the attained
      low extent of polymerization may lead to low bond strength, high susceptibility
      to degradation and also will favor a continuing etching effect on the underlying
      dentin.

PMID- 16430956
TI  - Mechanical characterization of resin cements used for luting fiber posts by
      nanoindentation.
AB  - OBJECTIVES: To evaluate the mechanical behavior of resin cements used for luting
      fiber post. The influence of the curing mode is analysed. METHODS:
      Nanoindentation techniques have been applied to determine hardness and Young's
      modulus of disc-shaped specimens of three types of cements: chemical- , photo-
      and dual-cured, provided by Ivoclar-Vivadent. Results obtained have been compared
      with measurements performed inside the post-cement-dentin system. Mechanical
      properties are evaluated together with scanning electron micrographs showing the
      post-cement and dentin-cement interfaces. RESULTS AND SIGNIFICANCE: Differences
      have been detected between mechanical measurements performed inside the post
      cement-dentin system and those carried out in laboratory disc-shaped specimens.
      The close presence of post and dentin boundaries has a lot of influence on the
      cement behavior. The nanoindentation measurements indicate that the photo-cured
      cement exhibits a high hardness and stiffness, but with a more marked tendency to
      brittle failure. The chemically cured cement is the material with higher ability
      to bear deformation without damage, although its hardness and elastic modulus are
      significantly lower. Dual-cured cements present the best combination of
      properties.

PMID- 16430957
TI  - Using hydroxyapatite nanoparticles and decreased crystallinity to promote
      osteoblast adhesion similar to functionalizing with RGD.
AB  - Better materials are needed to promote bone growth. For this reason, the present
      study created nanometer crystalline hydroxyapatite (HA) and amorphous calcium
      phosphate compacts functionalized with the arginine-glycine-aspartic acid (RGD)
      peptide sequence. Crystalline HA and amorphous calcium phosphate nanoparticles
      were synthesized by a wet chemical process followed by a hydrothermal treatment
      for 2 h at 200 degrees C and 70 degrees C, respectively. Resulting particles were
      then pressed into compacts. For the preparation of conventional HA particles (or
      those with micron diameters), the aforementioned pressed compacts were sintered
      at 1,100 degrees C for 2 h. Peptide functionalization was conducted by means of a
      three step reaction procedure: silanization with 3-aminopropyltriethoxysilane
      (APTES), cross-linking with N-succinimidyl-3-maleimido propionate (SMP), and
      finally peptide immobilization. The three step reaction procedure was
      characterized by a novel 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA)
      fluorescence technique. For all materials, results showed that the immobilization
      of the cell adhesive RGD sequence increased osteoblast (bone-forming cell)
      adhesion compared to those non-functionalized and those functionalized with the
      noncell adhesive control peptide (RGE) after 4 h. However, surprisingly, results
      also showed that the adhesion of osteoblasts on non-functionalized amorphous
      nanoparticulate calcium phosphate was similar to conventional HA functionalized
      with RGD. Osteoblast adhesion on nanocrystalline HA (unfunctionalized and
      functionalized with RGD) was below that of the respective functionalized
      amorphous calcium phosphate but above that of the respective functionalized
      conventional HA. In this manner, results of this study suggest that decreasing
      the particulate size into the nanometer regime and reducing crystallinity of
      calcium phosphate based materials may promote osteoblast adhesion to the same
      degree as the well-established techniques of functionalizing conventional HA with
      RGD.

PMID- 16430958
TI  - Uptake of functionalized, fluorescent-labeled polymeric particles in different
      cell lines and stem cells.
AB  - Labeling of cells with particles for in-vivo detection is interesting for various
      biomedical applications. The objective of this study was to evaluate the
      feasibility and efficiency labeling of cells with polymeric particles without the
      use of transfection agents. We hypothesized that surface charge would influence
      cellular uptake. The submicron particles were synthesized by the miniemulsion
      process. A fluorescent dye which served as reporter was embedded in these
      particles. The surface charge was varied by adjusting the amount of copolymerized
      monomer with amino group thus enabling to study the cellular uptake in
      correlation to the surface charge. Fluorescent-activated cell sorter (FACS)
      measurements were performed for detecting the uptake of the particles or
      attachment of particles in mesenchymal stem cells (MSC), and the three cell lines
      HeLa, Jurkat, and KG1a. These cell lines were chosen as they can serve as models
      for clinically interesting cellular targets. For these cell lines-with the
      exception of MSCs-a clear correlation of surface charge and fluorescence
      intensity could be shown. For an efficient uptake of the submicron particles, no
      transfection agents were needed. Confocal laser scanning microscopy and
      transmission electron microscopy (TEM) revealed differences in subcellular
      localization of the particles. In MSCs and HeLa particles were mostly located
      inside of cellular compartments resembling endosomes, while in Jurkat and KG1a,
      nanoparticles were predominantly located in clusters on the cell surface.
      Scanning electron microscopy showed microvilli to be involved in this process.

PMID- 16430959
TI  - In vitro spermatogenesis by three-dimensional culture of rat testicular cells in
      collagen gel matrix.
AB  - In an effort to improve in vitro spermatogenesis by potentiating the interactions
      between developing germ cells, somatic cells, and the extracellular matrix (ECM),
      the efficiency of the germ cell-somatic cell coculture in a three-dimensional
      (3D) collagen gel matrix was examined. Cells isolated from rat seminiferous
      tubules 18 days after birth were cultured for 22 days in a monolayer without ECM,
      collagen gel (CG), or collagen+Matrigel (CGM). After culture, the viabilities of
      the cultured cells in the monolayer, CG, and CGM culture were 42.8%, 70.7% and
      76.1%, respectively. Occludin-positive cells in a cyst-like structure were found
      in the ECM gel matrix together with 3beta hydroxysteroid dehydrogenase-positive
      cells, suggesting the presence of functional Sertoli cells and Leydig cells,
      respectively. Flow cytometric analysis of DNA content revealed a significant
      increase in the haploid cell population in the CG and CGM compared to the
      monolayer culture. Transition protein 2 (TP2) and protamine 2-positive cells were
      found together with a significant increase in TP2 mRNA levels in cells cultured
      in CG and CGM over those in monolayer culture, suggesting the occurrence of the
      post-meiotic differentiation of spermatogenetic cells. Taken together, a 3D in
      vitro culture system for testicular cells using a collagen gel matrix could
      enhance viability, meiosis, and post-meiotic differentiation of germ cells to
      presumptive differentiating spermatids.

PMID- 16430960
TI  - Development and adaptations of innate immunity in the gastrointestinal tract of
      the newly hatched chick.
AB  - The intestinal immune system in Gallus species must rapidly adapt to the
      omnivorous onset of an adult diet and to colonization by commensal bacteria. Yet,
      acquired immune functions in Gallus digestive tract fully develop only towards
      the end of the first week post-hatch. This raises the question of immune
      protection in the digestive tract during the first week of life. We postulated
      that in addition to protection conferred by maternal antibodies, the gut is
      protected by a functionally sufficient innate immune system at hatch. We studied
      granulocyte distribution in the gut as well as expression of functional genes
      representing different cells and activities of the innate immune system in
      chicken hatchlings. These included pro-inflammatory cytokines and chemokines (IL
      1beta, IL-8, K203), antibacterial beta-defensins, Gallinacin 1 and 2, and
      presenilin 1. We demonstrate innate preparedness in the developing chick gut in
      two circumstances: The first is independent of intestinal exposure to feed and
      bacteria and is manifested by heterophil maturation in situ. This gut-specific
      extramedullary granulopoietic process is reported for the first time in the
      chick, and is supported by beta-defensin and presenilin 1 gene expression. The
      second is responsive to environmental stimuli, and is demonstrated by gradual
      development of pro-inflammatory functions: Exposure of the gut to feed and
      bacteria triggered a low but significant increase in IL-1beta, IL-8 and K203.
      This resulted in the possible recruitment of bone marrow-derived heterophils as
      demonstrated by elevation of beta-defensin gene expression. The pro-inflammatory
      activity in the developing gut also explains the later recruitment of
      lymphocytes.

PMID- 16430961
TI  - Recombinant glutathione-S-transferase a major allergen from Alternaria alternata
      for clinical use in allergy patients.
AB  - Recombinant proteins are used for vaccines, therapy and diagnosis of many
      diseases. Biological activity of these may differ from native counterpart and
      needs investigation. The present study aimed to compare recombinant (r) and
      native (n) glutathione-S-transferase (GST) from Alternaria alternata. Glutathione
      S-transferase sequence showed an ORF of 696bp encoding 26-kDa protein with N
      terminus conserved domain. Secondary structure of both forms was comparable with
      melting temperature of 57 and 59 degrees C, respectively. rGST and nGST showed
      similar enzymatic activity, allergenicity and potency by ELISA inhibition.
      Histamine release was comparable in 14/17 patients for both the GSTs. rGST and
      nGST induced proliferation in PBMC at different concentration. Cell supernatant
      revealed higher IL-4 and IL-5 levels with low levels of IFN-gamma. In summary,
      recombinant and native GST demonstrated similar physio-chemical, biological and
      immunological properties and induced comparable cell mediated and humoral
      response to be used for diagnosis and specific immunotherapy for the fungal
      allergy cases.

PMID- 16430962
TI  - Loss of tolerance of anti-dsDNA B cells in mice overexpressing CD19.
AB  - Mice transgenic for the R4A-Cmu heavy chain of an anti-dsDNA antibody, maintain
      tolerance by anergy and deletion. In C57BL/6 mice overexpressing CD19, a
      molecule, which lowers the threshold for B cell activation, elevated levels of
      serum autoantibodies have been observed. In the present study, we wished to
      determine whether CD19 overexpression could alter the induction of tolerance in
      R4A-Cmu mice and lead to the secretion of transgenic anti-dsDNA antibodies. We,
      therefore, bred R4A-Cmu transgenic mice-to-mice transgenic for human CD19 (hCD19)
      and generated R4A-Cmu mice heterozygous and homozygous for hCD19. We, now report
      the spontaneous secretion of transgenic IgM anti-dsDNA antibody in the sera of
      R4A-Cmu mice overexpressing CD19, indicative of a loss of B cell tolerance. We
      observe that transgenic B cells secreting anti-dsDNA antibody in these mice are T
      independent and display a marginal zone like phenotype althought they do not
      reside in the MZ. In addition, they appear to be derived from the conventional B2
      subset rather than the B1 subset. Interestingly, a subset of the anti-dsDNA B
      cells in these mice still display the phenotype and functional characteristics of
      anergic B cells. These B cells cannot be activated to secrete antibody following
      BCR crosslinking, however, they are hyper-responsive to activation by innate
      signaling mechanisms. This suggests that CD19 overexpression may promote anergic
      B cells to escape tolerance by converging with BCR independent pathways, thereby
      rendering these B cells hyper-responsive to innate signaling.

PMID- 16430963
TI  - Membrane alterations and fluidity changes in cerebral cortex during acute ammonia
      intoxication.
AB  - Acute ammonia intoxication is known to cause alterations in activities of several
      membrane bound enzymes like Na+ K+ ATPase, acetylcholine esterase and glutamate
      uptake in brain. The alteration in these membrane associated activities could be
      a consequence of altered membrane architecture. To probe this, the effect of
      pathophysiological concentrations of ammonia on lipid composition and fluidity of
      membranes isolated from cerebral cortex of rats, were investigated in the present
      study. Administration of acute doses of ammonium acetate caused depletion of
      membrane sphingomyelin and cholesterol levels thereby reducing cholesterol:
      phospholipid (C: PL) ratio. Levels of phosphatidylserine increased while those of
      phosphatidylcholine and phosphatidylethanolamine remain unaltered. Membrane
      fluidity estimations using 1,6-diphenyl-1,3,5-hexatriene (DPH), 1-[4
      (trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) indicated no
      changes in core and surface membrane fluidity following ammonium acetate
      administration. Acute ammonia toxicity induced no alteration in bulk fluidity but
      a decrease in annular fluidity of membranes, as determined using pyrene
      fluorescence. Elevated levels of malondialdehyde and declined level of total
      thiols in cerebral cortex membranes of rats under acute ammonia intoxication
      indicated the existence of oxidative stress.

PMID- 16430964
TI  - Physiological function and putative therapeutic impact of the FGF-2 system in
      peripheral nerve regeneration--lessons from in vivo studies in mice and rats.
AB  - Diffusible and substratum-bound molecules regulate development and regeneration
      of the peripheral nervous system. The understanding of physiological function of
      these factors could have an impact on the development of new therapeutic
      strategies to stimulate nerve regeneration across long gaps. Within the group of
      trophic factors, basic fibroblast growth factor (FGF-2) and its high-affinity
      receptors are expressed in the intact peripheral nervous system and regulated
      following nerve injury. After exogenous application, FGF-2 promotes neuronal
      survival and neurite outgrowth in vitro and in vivo. In this review, animal
      studies on the physiological role of the endogenous FGF-2 system and the
      regenerative capacity after exogenous FGF-2 administration are summarized. The
      concept of FGF-2 function is discussed in context with other growth factors that
      are also physiologically relevant in the peripheral nervous system. Studies of
      sciatic nerve axotomy in FGF-2- and FGF receptor (R) 3-deleted mice,
      respectively, strongly suggested that FGF-2 binding to FGFR3 is involved in
      injury-induced neuronal apoptosis. At the lesion site, inhibition of myelination
      and stimulation of Schwann cell proliferation by FGF-2 via FGFR1/2 is suggested
      from rat and mouse studies, whereas neurite formation is very likely enhanced via
      FGFR3 activation. Additionally to these demonstrated physiological functions of
      endogenous FGF-2, administration of FGF-2 isoforms in the rat model of nerve
      regeneration across long gaps revealed a role of the high molecular weight
      isoforms of FGF-2 on sensory recovery. Within the group of physiologically
      relevant trophic factors, the FGF-2 system seems to be crucially involved in the
      scenario of peripheral nerve development and regeneration.

PMID- 16430965
TI  - Statistically robust detection of spontaneous, non-stereotypical neural signals.
AB  - Neural signals of interest are often temporally spontaneous and non-stereotypical
      in waveform. Detecting such signals is difficult, since one cannot use time
      locking or simple template-matching techniques. We have sought a statistical
      method for automatically estimating the baseline in these conditions, and
      subsequently detecting the occurrence of neural signals. One could consider the
      signals as outliers in the distribution of neural activity and thus separate them
      from the baseline with median-based techniques. However, we found that baseline
      estimators that rely on the median are problematic. They introduce progressively
      greater estimation errors as the neural signal's duration, amplitude or frequency
      increases. Therefore, we tested several mode-based algorithms, taking advantage
      of the most probable state of the neural activity being the baseline. We found
      that certain mode-based algorithms perform baseline estimation well, with low
      susceptibility to changes in event duration, amplitude or frequency. Once the
      baseline is properly established, its median absolute deviation (MAD) can be
      determined. One can then use it to detect spontaneous signals robustly as
      outliers from the noise distribution. We also demonstrate how the choice of
      detection threshold in terms of MADs can be used to bias against false positives,
      without creating too many false negatives or vice versa.

PMID- 16430966
TI  - Improved signal and reduced noise in neural recordings from close-spaced
      electrode arrays using independent component analysis as a preprocessor.
AB  - Noise can greatly complicate the isolation of individual cell action potential
      waveforms for the sake of electrophysiological analysis. For an experiment
      involving recording in the thalamus/subthalamus areas of a rat brain, a hybrid
      hardware/software method was utilized to improve the signal-to-noise quality of
      the recorded signal on each recording channel. The procedure uses closely spaced
      recording electrode arrays and independent component analysis (ICA) to fortify
      the signal energy of a single spike by combining input from several channels, and
      concurrently to reduce the noise on each channel by isolating common mode
      components such as artifacts, slow waves, and correlated distant spike
      activation. In the next step, a wavelet denoising-based signal-to-noise
      assessment is used to quantify the improvement in data quality for each data
      record. The data presented here demonstrate that this method, which can be
      applied off-line as a preprocessor to other time domain or transform domain spike
      sorting methods, is consistently effective at improving data quality and
      facilitating subsequent detection and classification of neurons.

PMID- 16430967
TI  - Standardization of a novel blood-sampling method through the jugular vein for use
      in the quantified [14C] 2-deoxyglucose method.
AB  - In the traditional [14C] deoxyglucose (2DG) method for the measurement of local
      cerebral glucose utilization (LCGU), blood samples are collected from the femoral
      artery. However, the placement of a femoral catheter can affect locomotor
      activity of the animal. We wanted to develop a new technique for blood sampling
      that would not interfere with the ongoing behavior. Therefore, the present report
      establishes a method of collecting blood samples for the 2DG method through the
      jugular vein. To calibrate this method, catheters were inserted in both the
      femoral artery and jugular vein of adult male Sprague Dawley rats. The next day,
      rats were injected with 2DG (125 microCi/kg) through the jugular vein. To
      quantify 14C in plasma, the standard method of blood collection was used for the
      femoral artery while syringes were used to extract blood samples from the jugular
      vein. We calculated the integrated specific activity of the plasma and final
      tissue 2DG concentrations based on Sokoloff's original equation using blood
      samples derived from both vessels. LCGU determined in selected brain regions was
      equivalent using both sampling methods. In conclusion, sampling from the jugular
      vein is appropriate for the quantified 2DG method and does not disrupt locomotor
      activity of the rat.

PMID- 16430968
TI  - Burden of phase-specific sexual dysfunction with SSRIs.
AB  - OBJECTIVE: This study examines phase-specific sexual dysfunction among patients
      who are being treated for major depression and who do not meet criteria for
      global sexual dysfunction. METHODS: 6297 adult outpatients receiving
      antidepressant monotherapy completed the Changes in Sexual Functioning
      Questionnaire (CSFQ). The sub-sample for this study (n = 3114) comprises
      participants who were receiving treatment with a SSRI or SNRI and did not meet
      the gender-specific criterion for global sexual dysfunction on the CSFQ. RESULTS:
      Among this sub-sample, 95.6% of women and 97.9% of men exhibited impairment in at
      least one phase of sexual functioning. Men were significantly more likely than
      women to experience dysfunction in the desire phase (91.2% vs. 79.0%; OR = 2.76;
      95% C.I. = 2.14 to 3.5) and the orgasmic phase (85.1% vs. 45.4%; OR = 6.9; 95%
      C.I. = 5.6 to 8.4) but were significantly less likely than women to experience
      dysfunction in the arousal phase (71.9% vs. 83.3%; OR = .51; 95% C.I. = .43 to
      .62). The prevalence of phase-specific dysfunction did not vary significantly by
      SSRI/SNRI for males or females. CONCLUSION: Among patients who do not experience
      clinically significant global sexual dysfunction on SSRI/SNRI monotherapy,
      dysfunction in at least one phase of the sexual response cycle is very common and
      may reduce sexual health-related quality of life.

PMID- 16430969
TI  - Possible connections among job stress, depressive symptoms, lipid modulation and
      antioxidants.
AB  - BACKGROUND: Oxidative/antioxidative status may be related to psychological stress
      or pathogenesis of depression. SUBJECTS AND METHODS: Participants were selected
      from 381 female nurses working in a university hospital, and the Brief Job Stress
      Questionnaire was utilized to assess them. Nurses with high job stress (JS) (n =
      18) and with low JS (n = 15) consented to participate in this study. Depressive
      symptoms were assessed by the Centre for Epidemiologic Studies Depression scale
      (CES-D). Cholesterols, lipid peroxidation (malondialdehyde, MDA) and antioxidants
      in the plasma were measured. RESULTS: High JS participants exhibited
      significantly higher CES-D scores (t = 3.34, p < 0.005), and significantly lower
      concentrations of total cholesterol (TC), low density+very low density
      lipoprotein cholesterols (LDL+VLDL), alpha-tocopherol, and beta-carotene compared
      with low JS participants (t = 2.69, p < 0.05; t = 3.46, p < 0.005; t = 2.96, p <
      0.05; t = 2.98, p < 0.05, respectively). However, the reductions in plasma
      indicators were substantially weakened after controlling for lifestyle factors
      with the exception of LDL+VLDL and alpha-tocopherol. In addition, the
      significance of alpha-tocopherol concentrations appeared to depend on cholesterol
      levels. CES-D scores correlated positively with plasma MDA levels, the MDA/TC
      ratio and the MDA/LDL+VLDL ratio among the low JS group (r = 0.69, p < 0.001; r =
      0.79, p < 0.001; r = 0.75, p < 0.005, respectively), whereas there were no
      correlations among the high JS group. After controlling for lifestyle covariates,
      the relationship between CES-D scores and the MDA/LDL+VLDL ratio remained
      significant (beta = 0.95, p < 0.05) using a multiple linear regression model (F =
      3.61, p < 0.05). LIMITATIONS: Sample numbers in each JS group were relatively
      small. CONCLUSIONS: Psychological stress may reduce the plasma levels of LDL+VLDL
      accompanying an alpha-tocopherol decrease. There appeared to be a correlation
      between elevated MDA and depressive symptoms in low JS participants.

PMID- 16430970
TI  - Differential expression analysis of proteins from neutrophils in the
      periparturient period and neutrophils from dexamethasone-treated dairy cows.
AB  - Neutrophils play an important role in the host immune system's defense against
      pathogens. It has been established that neutrophil functionality is suppressed in
      dairy cows at parturition. The periparturient immunosuppression seen in dairy
      cattle is associated with an increase in the incidence of mastitis. Using amine
      reactive isobaric tagging reagents we have measured relative protein expression
      from normal prepartum neutrophils and neutrophils isolated during
      immunosuppression at parturition. We found over 40 proteins that are
      differentially expressed at parturition compared to prepartum. In addition, we
      measured relative protein expression from normal neutrophils and neutrophils
      obtained from cows treated with an immunosuppressive dose of dexamethasone. We
      found over 70 proteins are differentially expressed during dexamethasone
      treatment. We then compared protein expression changes in dexamethasone-induced
      immunosuppression to periparturient immunosuppression. A number of proteins
      underwent similar expression changes in both dexamethasone and periparturient
      immunosuppressed neutrophils. Most significantly, we found a significant number
      of proteins whose relative expression was not the same for these two different
      conditions that cause neutrophil dysfunction. The data demonstrates that there
      are both similarities and differences in neutrophil protein expression in the
      naturally occurring immunosuppression observed at parturition compared to
      dexamethasone-induced immunosuppression in the bovine neutrophil.

PMID- 16430971
TI  - An IFNG polymorphism is associated with interferon-beta response in Spanish MS
      patients.
AB  - Interferon-beta is a biological treatment widely used in multiple sclerosis (MS).
      However, not every patient responds equally well to this therapy. In this study,
      our aim was to evaluate the influence of a dinucleotide microsatellite located in
      the first intron of the interferon-gamma gene on relapse eradication in a group
      of interferon-beta-treated patients. Our results show a very different allelic
      distribution when patients with relapses were compared with relapse-free
      patients.

PMID- 16430972
TI  - A real time PCR assay for the detection and quantification of orf virus.
AB  - A real time quantitative PCR assay based on TaqMan technology was developed for
      orf virus (ORFV) DNA quantification in clinical samples, infected cells and
      organotypic cultures. This method was based on the amplification of a 70 bp
      fragment from the ORFV B2L gene (orthologue of the Vaccinia virus Copenhagen F13L
      gene) that encodes the major envelope protein. Both intra- and inter-assay
      variability were well within +/-0.25 log(10) S.D. showing the high efficiency and
      reproducibility of the assay. The TaqMan PCR was subsequently used to determine
      the titre of several batches of the ORFV strain NZ-2, with it being possible to
      quantify virus solutions in the range of 1 x 10(1) to 1 x 10(6) TCID(50)/ml. A
      good correlation between the titre determined by the TaqMan PCR and by
      conventional endpoint dilution was found. The PCR assay is reproducible and can
      be used for a rapid quantification of ORFV in vitro and ex vivo, being readily
      achievable within 1h.

PMID- 16430974
TI  - Recent advances in Tourette syndrome research.
AB  - Tourette syndrome (TS) is a developmentally regulated neurobehavioral disorder
      characterized by involuntary, stereotyped, repetitive movements. Recent
      anatomical and neuroimaging studies have provided evidence for abnormal basal
      ganglia and dopaminergic function in TS. Basic research on striatal inhibitory
      mechanisms and dopaminergic function complements the recent neuroimaging and
      anatomical data. Parallel studies of basal ganglia participation in the normal
      performance and learning of stereotyped repetitive behaviors or habits has
      provided additional insight. These lines of research have provided new pieces to
      the TS puzzle, and their increasing convergence is showing how those pieces can
      be put together.

PMID- 16430973
TI  - Effective transduction of primary mouse blood- and bone marrow-derived
      monocytes/macrophages by HIV-based defective lentiviral vectors.
AB  - Human immunodeficiency virus type 1-based defective lentiviral vectors (HIV-based
      vector) efficiently transduce a wide range of mammalian cell types, but little is
      known with respect to their utility for gene transfer applications involving
      primary mouse monocytes/macrophages. This may be important for preclinical
      development of a range of potential gene therapeutic modalities. Present study
      described the development of an optimized method for viral vector-mediated gene
      transfer into primary mouse monocytes/macrophages and the establishment of
      reproducible protocols for cell isolation/cultivation. It has been determined
      that bone marrow-derived monocytes/macrophages were consistently more susceptible
      to viral vector-mediated gene transduction, as compared to blood-derived cells.
      It has also been documented that the efficiency of transduction increased when
      cells were maintained in vitro, prior to exposure to vector virus. Finally,
      experiments were conducted to compare the efficiency of gene transfer mediated by
      HIV-based vectors to that achieved by other lentivirus or retrovirus vector
      systems. These studies showed that HIV-based vector system was consistently
      superior. Overall, these results establish a new and efficient method for gene
      transfer into primary mouse monocytes/macrophages. This may be of utility in the
      preclinical development of gene therapies that target this important cell type.

PMID- 16430975
TI  - Protective immunity against acute phleboviral infection elicited through
      immunostimulatory cationic liposome-DNA complexes.
AB  - Cationic liposome-DNA complexes (CLDC) have been demonstrated to induce potent
      antitumor activities. The ability of these complexes to elicit protective
      immunity against viral infections has not been fully explored. Here we report
      findings on the use of CLDC as an antiviral agent in a mouse model of acute
      phleboviral (Punta Toro virus) disease. CLDC treatment of mice challenged with
      Punta Toro virus (PTV) resulted in dramatic increases in survival and reduced
      viral burden and other parameters indicative of protection against disease. CLDC
      were effective when administered by intraperitoneal and intravenous routes and
      elicited protective immunity when given within 1 day of virus challenge.
      Treatments administered 36 h or longer after challenge, however, were not
      effective in preventing mortality or disease. CLDC treatment induced release of a
      number of potential antiviral cytokines including IFN-gamma, IL-12, and IFN
      alpha. Taken together, our findings indicate that non-specific immunotherapy with
      CLDC appears to be an effective treatment for blocking PTV-induced disease and
      suggests that further exploration in other viral disease models may be warranted.

PMID- 16430976
TI  - Kinematic features of movement tunes perception and action coupling.
AB  - How do we extrapolate the final position of hand trajectory that suddenly
      vanishes behind a wall? Studies showing maintenance of cortical activity after
      objects in motion disappear suggest that internal model of action may be recalled
      to reconstruct the missing part of the trajectory. Although supported by
      neurophysiological and brain imaging studies, behavioural evidence for this
      hypothesis is sparse. Further, in humans, it is unknown if the recall of internal
      model of action at motion observation can be tuned with kinematic features of
      movement. Here, we propose a novel experiment to address this question. Each
      stimulus consisted of a dot moving either upwards or downwards, and corresponding
      to vertical arm movements that were masked in the last part of the trajectory.
      The stimulus could either move according to biological and or non-biological
      kinematic laws of pointing tasks. We compared subjects' estimations of the
      stimulus vanishing or final positions after biological and after non-biological
      motion displays. Subjects systematically overestimated the vanishing and final
      position for the two directions (up and down) and the two kinematics displayed
      (biological and non-biological). However, estimation of the final position
      decreased in precision and increased in variability for movements that violated
      the kinematic laws of arm pointing task. The results suggest that motion
      inference does not rely only upon visual extrapolating mechanisms based on past
      visual trajectory information. We propose that motion estimation relies on
      internal models that contain specific kinematic details of vertical arm movement,
      which can be rapidly recalled during motion observation.

PMID- 16430977
TI  - Sub-cellular partitioning of cadmium, copper, nickel and zinc in indigenous
      yellow perch (Perca flavescens) sampled along a polymetallic gradient.
AB  - Sub-cellular metal distributions were studied in indigenous yellow perch (Perca
      flavescens) collected from eight lakes located along a cadmium (Cd), copper (Cu),
      nickel (Ni) and zinc (Zn) concentration gradient. Ambient dissolved metal
      concentrations were measured to evaluate exposure and total hepatic metal
      concentrations were determined as a measure of metal bioaccumulation. Metal
      partitioning among potentially metal-sensitive fractions (cytosolic enzymes,
      organelles) and detoxified metal fractions (metallothionein) was determined after
      differential centrifugation of fish liver homogenates. Major proportions of
      hepatic Cd and Cu were found in the heat-stable cytosolic peptides and proteins
      fraction (HSP), a fraction including metallothioneins, whereas the potentially
      metal-sensitive heat-denaturable proteins fraction (HDP) was the largest
      contributor to the total Ni and Zn burdens. The concentrations of Cd, Cu and Ni
      (but not Zn) in each sub-cellular fraction increased along the metal
      contamination gradient, but the relative contributions of each fraction to the
      total burden of each of these metals remained generally constant. For these
      chronically exposed fish there was no threshold exposure concentration below
      which binding of Cd or Ni to the heat-denaturable protein fraction did not occur.
      The presence of Cd and Ni in the HDP fraction, even for low chronic exposure
      concentrations, suggests that metal detoxification was imperfect, i.e. that P.
      flavescens was subject to some metal-related stress even under these conditions.

PMID- 16430978
TI  - Expression profiling by whole-genome interspecies microarray hybridization
      reveals differential gene expression in procyclic promastigotes, lesion-derived
      amastigotes, and axenic amastigotes in Leishmania mexicana.
AB  - We examined the Leishmania mexicana transcriptome to identify differentially
      regulated mRNAs using high-density whole-genome oligonucleotide microarrays
      designed from the genome data of a closely related species, Leishmania major.
      Statistical analysis on array hybridization data representing 8156 predicted
      coding regions revealed 288 genes (3.5% of all genes) whose steady-state mRNA
      levels meet criteria for differential regulation between promastigotes and lesion
      derived amastigotes. Interestingly, sample comparison of promastigotes to axenic
      amastigotes resulted in only 17 genes (0.2%) that meet the same statistical
      criteria for differential regulation. The reduced number of regulated genes is a
      consequence of an increase in the magnitude of the transcript levels in cells
      under axenic conditions. The expression data for a subset of genes was validated
      by quantitative PCR. Our studies show that interspecies hybridization on
      microarrays can be used to analyze closely related protozoan parasites, that
      axenic culture conditions may alter amastigote transcript abundance, and that
      there is only a relatively modest change in abundance of a few mRNAs between
      morphologically distinct promastigote and amastigote cultured cells. Leishmania
      may represent an alternative paradigm for eukaryotic differentiation with minimal
      contributions from changes in mRNA abundance.

PMID- 16430979
TI  - Risk factors for Campylobacter spp. colonization in broiler flocks in Iceland.
AB  - We sampled 1,091 Icelandic broiler flocks at slaughter from May 2001 to December
      2003 to determine the prevalence of, and investigate risk factors for the
      presence of, Campylobacter spp. at the flock level. Approximately 15% of the
      flocks were positive for Campylobacter spp.; most (95%) of the infected flocks
      being raised during the months of April-September. Based on the data from the
      latter months, and using multivariable logistic regression with random effects
      for herd, we found that the odds of a flock being positive for Campylobacter spp.
      increased with age and flock size. Additionally, vertical ventilation systems
      were strongly associated with positive flocks (OR=5.3). After controlling for
      these variables, we found no evidence of an effect of: year; company;
      Campylobacter being carried over from one flock to the next; time interval
      between flocks; using (at the hatcheries) eggs laid on the floor; density of bird
      housing, or the number of catch lots a flock was divided into for slaughtering
      purposes on the risk of a Campylobacter-positive flock.

PMID- 16430980
TI  - The effect of hen-egg antibodies on Clostridium perfringens colonization in the
      gastrointestinal tract of broiler chickens.
AB  - We evaluated the ability of hen-egg antibodies (HEA) to reduce intestinal
      colonization by Clostridium perfringens in broiler chickens. Antibodies against
      C. perfringens or cholera toxin (negative control) were obtained from the eggs of
      laying hens hyperimmunized using a C. perfringens bacterin or cholera toxin. Eggs
      were collected, pooled, and egg antibodies were concentrated by polyethylene
      glycol precipitation. An initial experiment was conducted to determine the in
      vivo activity of the administered antibody along the length of the intestine.
      Thereafter, two feeding trials were performed to assess the efficacy of feed
      amended with the egg antibodies in reducing the level of colonization of C.
      perfringens in challenged birds. Antibody activity declined from proximal to
      distal regions of the intestine but remained detectable in the cecum. In the
      first experiment there was no significant reduction in the number of C.
      perfringens in the birds fed the diet amended with the anti-C. perfringens egg
      antibody, compared to the birds that received the anti-cholera toxin egg antibody
      (n=10), at any of the sampling times. In the second experiment there was a
      significant decrease in C. perfringens intestinal populations 72 h after
      treatment (n=15) as assessed by culture-based enumeration, but there was no
      decrease as measured by quantitative PCR based on the C. perfringens
      phospholipase C gene. Intestinal-lesion scores were higher in the birds that
      received the anti-C. perfringens HEA. Our work suggests that administration of
      HEA did not reduce the level of C. perfringens intestinal colonization and
      conversely might exacerbate necrotic enteritis.

PMID- 16430981
TI  - Uncovering the relationship between defence and orienting in emotion: cardiac
      reactivity to unpleasant pictures.
AB  - This research was aimed at studying the relationship between the cardiovascular
      reactivity to an intense auditory stimulus and the subsequent cardiac response
      evoked by affective visual stimuli in fifty-five subjects who underwent a cardiac
      reactivity task (presentation of an intense acoustic stimulus), followed by a
      picture viewing task (54 pictures selected from the International Affective
      Picture System). Heart rate (HR), electrodermal activity and corrugator
      supercilii electromyographic activity were recorded. Subjects were divided into
      two groups - high accelerators and low accelerators - on the basis of the first
      heart rate acceleration obtained in the cardiac reactivity task. Pictures evoked
      different cardiac response patterns in each subject group. Unpleasant pictures
      promoted a lower initial HR deceleration and a higher final acceleration in high
      accelerators than in low accelerators. This pattern of response was more marked
      with body damage pictures. Moreover, a relationship was found between the first
      acceleration promoted by the acoustic stimulus and the HR response waveform to
      the body damage pictures. These results show that, in an unselected sample of
      subjects, a subgroup tended to respond to loud stimuli with higher HR
      acceleration and sympathetic activation and to respond defensively to unpleasant
      pictures (as found by less initial HR deceleration and higher final HR
      acceleration), rather than manifesting an orienting response. The elicitation of
      the defence response by a brain fear system, in which the amygdala is a key
      structure, is also discussed.

PMID- 16430982
TI  - The hypothalamic-pituitary-adrenocortical axis in addiction.

PMID- 16430983
TI  - Cladal relatedness among Aspergillus oryzae isolates and Aspergillus flavus S and
      L morphotype isolates.
AB  - Aspergillus flavus is the main etiological agent for aflatoxin contamination of
      crops. Its close relative, A. oryzae, does not produce aflatoxins and has been
      widely used to produce fermented foods. We compared the phylogeny of A. oryzae
      isolates and L- and S-type sclerotial isolates of A. flavus using single
      nucleotide polymorphisms in the omtA gene in the aflatoxin biosynthesis gene
      cluster and deletions in and distal to the norB-cypA intergenic region as
      phylogenetic signals. Aflatoxin-producing ability and sclerotial size also were
      weighted in the analysis. Like A. flavus, the A. oryzae isolates form a
      polyphyletic assemblage. A. oryzae isolates in one clade strikingly resemble an
      A. flavus subgroup of atoxigenic L-type isolates. All toxigenic S-type isolates
      closely resemble another subgroup of atoxigenic L-type isolates. Because
      atoxigenic S-type isolates are extremely rare, we hypothesize that loss of
      aflatoxin production in S-type isolates may occur concomitantly with a change to
      L-type sclerotia. All toxigenic L-type isolates, unlike A. oryzae, have a 1.0 kb
      deletion in the norB-cypA region. Although A. oryzae isolates, like S-type, have
      a 1.5 kb deletion in the norB-cypA region, none were cladally related to S-type
      A. flavus isolates. Our results show that A. flavus populations are genetically
      diverse. A. oryzae isolates may descend from certain atoxigenic L-type A. flavus
      isolates.

PMID- 16430984
TI  - Sequence variation in the Newcastle disease virus genome.
AB  - Full-length genome sequences of five virulent and five avirulent strains of
      Newcastle disease virus isolated between 1998 and 2002 in Victoria and New South
      Wales, Australia were determined. Comparisons between these strains revealed that
      coding sequence variability in the haemagglutinin-neuraminidase (HN), matrix (M)
      and phosphoprotein (P) gene sequences appeared to be more variable than in the
      fusion (F), nucleocapsid (N) and RNA dependent-RNA replicase (L) genes. Sequence
      analysis of a number of other isolates made during the recent virulent NDV
      outbreaks, also identified the presence of a number of variants with altered F
      gene cleavage sites, which resulted in altered biological properties of those
      viruses. Quasispecies analysis of a number of field isolates indicated the
      presence of virulent virus in one particular isolate. Gene sequence analysis of
      the progenitor virus isolated in 1998 showed very little sequence variation when
      compared to that of a progenitor-like virus isolated in 2001, demonstrating that
      in the field, viral genome sequence variation appears to be biologically
      restricted to that of a consensus sequence.

PMID- 16430985
TI  - Genetic characterization of the Capra hircus papillomavirus: a novel close-to
      root artiodactyl papillomavirus.
AB  - The healthy skin of a seven-year-old female goat (Capra hircus) was sampled with
      a cotton tip swab. Total genomic DNA was extracted from the sample and subjected
      to multiply primed rolling-circle amplification (RCA). Restriction analysis
      showed that the complete genome of a papillomavirus was amplified, measuring
      approximately 7,600 bp in length. The Capra hircus papillomavirus (ChPV-1) genome
      was cloned from this rolling-circle amplification product, and the complete
      nucleotide sequence was determined. The ChPV-1 genome counts 7,542 bp, and
      contains the typical papillomaviral open reading frames (ORFs). Based on a
      concatenated alignment of the E1, E2, L1 and L2 open reading frames of ChPV-1 and
      54 other animal and human papillomavirus types, a neighbor-joining phylogenetic
      tree was constructed. In this tree ChPV-1 clusters with BPV-3, -4 and -6.
      Pairwise nucleotide sequence alignments of the L1 open reading frame of ChPV-1
      with its closest relatives showed less than 60% similarity, placing the ChPV-1 in
      a novel genus.

PMID- 16430987
TI  - Critical freezing rate in freeze drying nanocrystal dispersions.
AB  - Recent advances in nanoparticle technologies have significantly enhanced the oral
      and parenteral delivery of poorly water-soluble active pharmaceutical ingredients
      (APIs). However, reports have been limited on the various drying procedures to
      convert a liquid nanocrystal dispersions into solid dosage forms. The solid
      dosage form should consist of nanocrystals that can readily reconstitute into
      their original size upon dissolution in water. Herein, the freeze drying process
      of nanocrystal dispersions was examined at varying freezing rates (speed of
      freezing interface). As freezing rate decreases, more particle-particle
      aggregation developed. A critical freezing rate, below which the dried
      nanocrystals cannot be re-dispersed, was identified based on the plot of the
      particle size of reconstituted nanocrystals versus freezing rate. Freeze drying
      at a freezing rate near the critical value produces dry powders of bimodal
      particle size distribution after re-dispersion. In addition, API concentration
      was found to significantly affect the critical freezing rate and therefore the re
      dispersibility of dry powders. The concept of critical freezing rate is critical
      for the development of solid dosage forms of liquid nanocrystal dispersions.

PMID- 16430986
TI  - Modeling the release of proteins from degrading crosslinked dextran microspheres
      using kinetic Monte Carlo simulations.
AB  - To optimize and predict the release of proteins from biodegradable microspheres
      based on crosslinked dextran, a fundamental understanding of the mechanisms
      controlling their release is necessary. For that purpose, a mathematical model
      has been developed to describe the release of proteins from these hydrogel-based
      microspheres. A kinetic Monte Carlo scheme for the degradation of a small domain
      inside the microsphere was developed. The results from this were used in a second
      kinetic Monte Carlo scheme to model the diffusion and the subsequent release of
      proteins. The only processes included in this model are diffusion and
      degradation. The general effects of diffusion, crosslink density, protein
      loading, and clustering of proteins on the release were investigated. The model
      crosslink density (Xmodel) and the model diffusivity (Dmodel) were fitted to
      experimental release data of BSA monomer from hydroxyethyl methacrylated dextran
      (dex-HEMA) microspheres. By using the experimental release curves of liposomes
      and BSA monomer, it was found that (1) the model crosslink density (Xmodel)
      scales with the hydrodynamic diameter (dh) as dh(1.64) and (2) the diffusivity of
      the protein (Dmodel) scales approximately with 1/dh (Stokes-Einstein). Using
      these scaling relations, quantitative predictions of the release curves of BSA
      dimer, immunoglobulin G and human growth hormone were possible. In conclusion,
      this model may play an important role in the optimization, understanding and
      prediction of the release of various proteins from degradable hydrogels.

PMID- 16430988
TI  - [Two cases of rehabilitation in Ehler-Danlos syndrome].
AB  - PURPOSE: Ehlers-Danlos syndrome is rare and little known. It comprises a
      heterogeneous group of heritable connective tissue disorders characterized by
      articular hypermobility, skin extensibility and tissue fragility. Diagnosis may
      be difficult and often delayed. CASE REPORT: Here we describe 2 cases of women
      with Ehlers-Danlos syndrome. The first had scoliosis with back pain and joint
      hypermobility. The second presented with hypermobility and joint dislocation,
      which increased during pregnancy. In these 2 cases, rehabilitation management
      produced clinical improvement. DISCUSSION: Orthopaedic complications such joint
      pain, joint swelling, joint dislocation, back pain, with walking and hand
      function disability are the main problems in Ehlers-Danos syndrome. Surgery may
      be necessary to correct dislocated joints but is often not sufficient to resolve
      the handicap, and physical therapy has an important place in management.
      CONCLUSION: Ehlers-Danlos syndrome is an evolving disease that can lead to great
      impairment. Thus, physicians must be aware of this syndrome to offer the best
      management, with the appropriate use of orthotic devices, specific strengthening
      routines, education in proper body mechanics and assistive devices, to prevent
      joint dislocation and subluxations responsible for pain and handicap.

PMID- 16430989
TI  - A pan-Canadian perspective on institutional long-term care.
AB  - We aggregate long-term care (LTC) facility-level data collected by Statistics
      Canada to National and regional levels to make observations relating to
      environmental characteristics--including the age distribution by region, and
      market share by type of ownership--and organizational characteristics--including
      ownership, facility size, resident age distribution, and the types of care
      provided in facilities by ownership. We observe significant differences in
      ownership by region, in facility size by ownership, and in levels of resident
      care provided by ownership. Further, we examine some of the classic proxies for
      quality of care for the LTC sector in this paper, including a variety of staffing
      intensity levels, observing significant differences in staffing intensities by
      region. We hope that our observations prompt researchers and policy makers to
      question the desirability and implications of this variation in the Canadian LTC
      industry.

PMID- 16430990
TI  - Regulation of gene expression by alternative untranslated regions.
AB  - The untranslated regions of mRNAs can determine gene expression by influencing
      mRNA stability and translational efficiency. Recent reports show that gene
      expression can be regulated by the differential use of alternative untranslated
      regions. Tissue-specific expression of transcripts that have different
      untranslated regions (UTRs) can control protein expression enabling
      developmental, physiological and pathological regulation. Several examples of
      alternative UTRs have been characterized, including those found in AXIN2, FGF1
      and BRCA1. Results from bioinformatics studies indicate that this mechanism is
      more common than previously appreciated.

PMID- 16430992
TI  - Brain event-related potentials: diagnosing early-stage Alzheimer's disease.
AB  - A pattern of components from brain event-related potentials (ERPs) (cognitive non
      invasive electrical brain measures) performed well in separating early-stage
      Alzheimer's disease (AD) subjects from normal-aging control subjects and shows
      promise for developing a clinical diagnostic for probable AD. A Number-Letter
      task elicited brain activity related to cognitive processes. In response to the
      task stimuli, brain activity was recorded as ERPs, whose components were measured
      by principal components analysis (PCA). The ERP component scores to relevant and
      irrelevant stimuli were used in discriminant analyses to develop functions that
      successfully classified individuals as belonging to an early-stage Alzheimer's
      disease group or a like-aged Control group, with probabilities of an individual
      belonging to each group. Applying the discriminant function to the developmental
      half of the data showed 92% of the subjects were correctly classified into either
      the AD group or the Control group with a sensitivity of 1.00. The two
      crossvalidation results were good with sensitivities of 0.83 and classification
      accuracies of 0.75-0.79. P3 and CNV components, as well as other, earlier ERP
      components, e.g. C145 and the memory "Storage" component, were useful in the
      discriminant functions.

PMID- 16430993
TI  - Synthesis and bronchodilator activity of new quinazolin derivative.
AB  - Taking lead from a naturally occurring quinazolin vasicine, a number of compounds
      were developed and evaluated for bronchodilator and anti-allergic activities. One
      of these compounds was 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino[2,1
      b]quinazolin-12-one, hereinafter named 95-4, exhibited marked bronchodilator
      activity evaluated on contracted trachea or constricted tracheo-bronchial tree.
      On intestinal smooth muscle too it showed relaxant effect. Tracheal relaxant
      effect was not found to be mediated through beta-adrenoceptors. Cumulative dose
      response study with acetylcholine and histamine indicated for its non-specific
      direct effect on smooth muscles. 95-4 was found to be more potent than
      theophylline and less to that of salbutamol on dose basis. Tested by a number of
      experimental models, it was found devoid of anti-allergic activity. It was also
      found to be free from any adverse effect. 95-4 due to its marked bronchial muscle
      relaxant effect can find use in conditions associated with spasm of bronchial
      muscles.

PMID- 16430994
TI  - Are vaccination information leaflets useful for vaccinators and parents?
AB  - Three vaccination information leaflets (VIL) were evaluated in the province of
      Quebec in 2002-2003 to examine their use by vaccinators (nurses and physicians),
      and their success in reaching parents of infants and toddlers. Data were
      collected from vaccinators and parents by postal survey. Reception of all of the
      VIL was higher among nurses (98%) than among physicians (39%). Only 14% of
      parents were familiar with all the VIL. Vaccinators who used the VIL, and the
      parents who were familiar with them, were satisfied with their presentation,
      clarity, quantity of information, pertinence and credibility. While the
      information leaflets were useful for vaccinators, few parents were reached,
      limiting the impact of this method of promotion.

PMID- 16430995
TI  - Recombinant Mannheimia haemolytica serotype 1 outer membrane protein PlpE
      enhances commercial M. haemolytica vaccine-induced resistance against serotype 6
      challenge.
AB  - Mannheimia haemolytica outer membrane protein PlpE, a major immunogenic outer
      membrane lipoprotein has identical sequences in serotypes 1 (S1) and S6.
      Recombinant outer membrane lipoprotein PlpE (rPLpE) from M. haemolytica S1 was
      added to commercial M. haemolytica S1 vaccines to determine if it would enhance
      vaccine-induced immunity against heterotypic M. haemolytica S6 challenge. Serum
      antibody responses to M. haemolytica whole cells, leukotoxin and rPlpE were
      measured. Experiment 1 consisted of four vaccine groups: controls, 100 microg
      rPlpE, M. haemolytica Bacterin-Toxoid (One Shot) and M. haemolytica Bacterin
      Toxoid + 100 microg rPlpE. Vaccines were given on day 0. On day 21, calves were
      challenged transthoracically with M. haemolytica S6. Lung lesion scores and
      percentage lesion reduction were 6.3 +/- 2.0 for controls, 3.6 +/- 2.4 for rPlpE
      vaccinates (42.9% reduction), 3.4 +/- 1.5 for One Shot-vaccinates (46.0%
      reduction), and 2.4 +/- 1.4 for One Shot/rPlpE vaccinates (61.9% reduction).
      Experiment 2 consisted of four vaccine groups: controls, 100 microg rPlpE, M.
      haemolytica toxoid (Presponse), and M. haemolytica toxoid+100 microg rPlpE. On
      day 28, calves were challenged transthoracically with M. haemolytica S6. Lung
      lesion scores and percentage lesion reduction were 8.1 +/- 2.2 for controls, 4.4
      +/- 4.7 for the rPlpE vaccinates (45.7% reduction), 4.8 +/- 2.2 for Presponse
      vaccinates (40.7% reduction), and 2.0 +/- 1.2 for Presponse/rPlpE vaccinates
      (75.3% reduction). These results indicate that addition of rPlpE from M.
      haemolytica S1 can enhance commercial M. haemolytica vaccine-induced resistance
      against experimental challenge with M. haemolytica S6.

PMID- 16430996
TI  - Unexpected inefficiency of the European pharmacopoeia sterility  test for
      detecting contamination in clostridial vaccines.
AB  - Three outbreaks of clostridial disease in ruminants were reported in Spain. Out
      of 202,525 animals in affected herds, 41,767 were infected and 22,189 died.
      Epidemiological investigation linked these outbreaks with vaccination with three
      different commercial anti-clostridial vaccines contaminated with Clostridium
      sordellii. Vaccines were produced by the same manufacturer. Microbiological and
      molecular genetic analyses confirmed this association, and isolates of C.
      sordellii with identical biochemical and pulsed-field gel electrophoresis (PFGE)
      macrorestriction patterns were isolated from both diseased animals and the
      epidemiologically related vaccines. Contamination of the commercial vaccines was
      not detected by the sterility test proposed by the European (EU) Pharmacopoeia.
      However, growth was obtained when the commercial vaccines were inoculated into
      specific culture media for Clostridium and incubated for up to 60 days.

PMID- 16430997
TI  - Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic
      orthopoxvirus challenge.
AB  - The possible reemergence of smallpox through bioterrorism requires the
      preparation of adequate stockpiles of vaccine. Dryvax, the only US-licensed
      vaccinia virus smallpox vaccine, has an unacceptable safety profile in the pre
      event setting. LC16m8 is a Japanese-licensed attenuated vaccinia virus strain
      that has been safely used in over 50,000 persons. Until now, efficacy of this
      vaccine was unproven. Using two animal models, we show that LC16m8 and Dryvax
      elicit comparable humoral immune responses after a single vaccination and
      equivalently protect against lethal poxvirus disease. Thus, LC16m8 shows promise
      as a safe and effective smallpox vaccine with the potential for replacing Dryvax.

PMID- 16430998
TI  - Forty years of 90Sr in situ migration: importance of soil characterization in
      modeling transport phenomena.
AB  - In 1960 experiments were carried out on the transfer of (90)Sr between soil,
      grapes and wine. The experiments were conducted in situ on a piece of land
      limited by two control strips. The (90)Sr migration over the last 40 years was
      studied by performing radiological and physico-chemical characterizations of the
      soil on eight 70 cm deep cores. The vertical migration modeling of (90)Sr
      required the definition of a triple layer conceptual model integrating the
      rainwater infiltration at constant flux as the only external factor of influence.
      Afterwards the importance of a detailed soil characterization for modeling was
      discussed and satisfactory simulation of the (90)Sr vertical transport was
      obtained and showed a calculated migration rate of about 1.0 cm year(-1) in full
      agreement with the in situ measured values. The discussion was regarding some of
      the key parameters such as granulometry, organic matter content (in the Van
      Genuchten parameter determination), Kd and the efficient rainwater infiltration.
      Besides the experimental data, simplifying assumptions in modeling such as water
      soil redistribution calculation and factual discontinuities in conceptual model
      were examined.

PMID- 16430999
TI  - Patterns and inventories of radioactive contamination of island sites of the
      Yenisey River, Russia.
AB  - The distribution of radioactive contamination at three island sites downstream
      from the Krasnoyarsk Mining and Chemical Combine (KMCC) was studied with the
      objectives of mapping contamination levels, interpreting radionuclide
      distributions through consideration of alluvial processes and determining
      radionuclide inventories. Contamination was measured using in situ gamma
      spectrometry and landforms characterised using topographic surveying methods.
      Maximum (137)Cs contamination densities (700 kBq m(-2)) were found on low- and
      middle-level floodplains and low-lying interconnecting areas of Beriozovy Island
      (16 km from the KMCC). On Mikhin Island (180 km from the KMCC) maximum total
      (60)Co, (152)Eu and (154)Eu activity concentrations (30-40 kBq m(-2)) occur in
      low-lying areas inundated during flooding. Maximum (137)Cs and total (60)Co,
      (152)Eu and (154)Eu contamination densities on Cheriomukhov Island (250 km from
      the KMCC) were 390 and 50 kBq m(-2), respectively. Estimated (137)Cs inventories
      were 145, 148 and 16GBq for Beriozovy, Mikhin and Cheriomukhov Islands,
      respectively.

PMID- 16431000
TI  - Endoscopic removal of a dental implant through a middle meatal antrostomy.
AB  - Ear nose and throat surgeons use endoscopic operations on the sinuses not only
      for chronic paranasal sinusitis but also for other operations. We report the case
      of a 52-year-old woman in whom we used an endoscopic technique to remove a dental
      implant that had been displaced into the maxillary sinus. We approached the sinus
      through the natural ostium, and the foreign body was removed through the widened
      ostium.

PMID- 16431001
TI  - Assessment of the fixation stiffness of some femoral stems of different designs.
AB  - BACKGROUND: Appropriate contour design of a femoral stem is important for the
      secure primary fixation. Although the relationship between the contour and stress
      or micro-motion at the fixation site has been analyzed, guidelines on stem design
      have not been established. METHODS: Different kinds of finite element models of
      three femoral stems were constructed for computer simulation. These models had
      the contour designs that head for the tight mechanical fixation by the different
      ways, respectively. Boundary and initial conditions were (i) rigid contact of the
      distal end of the model femur with the rigid base. (ii) Stepping load of 800 N or
      1800 N was applied to the proximal top of the stem. (iii) Stepping load of 640 N
      or 1440 N was pulled from the greater trochanter of the femur as muscle force.
      The ratio of displacement to the vertical load, which was defined as fixation
      stiffness, was calculated. FINDINGS: The mean displacement of the intra-medullary
      cruciate stem was 27.6 nm. For the VerSys stem with sharp fins, the mean
      displacement was 32.9 nm. For the PerFix SV stem with a flange, the mean
      displacement was 52.8 nm. Vertical fixation stiffness estimated on the intra
      medullary cruciate stem, the VerSys stem, and the PerFix SV stem was 461, 264,
      and 313 MN/mm, respectively. INTERPRETATION: Contour design of a femoral stem is
      important for achieving secure fixation, which prevents loosening. We introduce
      fixation stiffness as a measure to theoretically evaluate the primary fixation of
      femoral stems.

PMID- 16431002
TI  - Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double
      blind, randomized, placebo-controlled trial.
AB  - The safety profile of Coenzyme Q10 (Kaneka Q10) at high doses for healthy
      subjects was assessed in a double-blind, randomized, placebo-controlled study.
      Kaneka Q10 in capsule form was taken for 4 weeks at doses of 300, 600, and 900
      mg/day by a total of eighty-eight adult volunteers. No serious adverse events
      were observed in any group. Adverse events were reported in 16 volunteers with
      placebo, in 12 volunteers with the 300 mg dose, in 20 volunteers with the 600 mg,
      dose and in 16 volunteers with the 900 mg dose. The most commonly reported events
      included common cold symptoms and gastrointestinal effects such as abdominal pain
      and soft feces. These events exhibited no dose-dependency and were judged to have
      no relationship to Kaneka Q10. Changes observed in hematology, blood
      biochemistry, and urinalysis were not dose-related and were judged not to be
      clinically significant. The plasma CoQ10 concentration after 8-month withdrawal
      was almost the same as that before administration. These findings showed that
      Kaneka Q10 was well-tolerated and safe for healthy adults at intake of up to 900
      mg/day.

PMID- 16431003
TI  - The nature and correlates of unmet health care needs in Ontario, Canada.
AB  - Using data from the Canadian Community Health Survey (CCHS) Cycle 1.2, we examine
      the nature of unmet mental health care needs in Ontario, Canada and how this is
      associated with socio-demographic, social support, health status and mental
      health service use factors. Unmet mental health care needs result from
      experiencing barriers to three issues: acceptability, accessibility and
      availability. Unmet needs due to acceptability issues are the most frequent type;
      the largest proportion of people within this category report experiencing unmet
      needs because they "preferred to manage the problem themselves". Unmet needs are
      greater among the young and among females. Surprisingly, service users report
      higher rates of unmet needs than non-users. Some social support variables have
      associations with unmet needs. Based upon these results, unmet needs pose a major
      challenge to the health care system since they cannot be resolved solely by
      enhancing access to and availability of mental health services. Thus, to address
      unmet mental health care needs, efforts should be focused on the acceptability
      barriers that women and young people in particular face. Enhancing education and
      certain social support mechanisms are potential strategies.

PMID- 16431004
TI  - Cancer in the mass print media: fear, uncertainty and the medical model.
AB  - Cancer is increasing in incidence and prevalence in North America and around the
      world. The mass print media play an important role in information provision about
      prevention, diagnosis and treatment of this disease, as well as informing health
      policy and personal experience. This paper reports on a content analysis of the
      portrayal of cancer in the highest circulating magazines available in Canada and
      published in Canada or the USA in 1991, 1996, 2001. It includes both manifest and
      latent analysis of the framing and content of cancer stories. Manifest analysis
      documented the dominance of the medical as compared to the lifestyle and
      political economy frames and the predominance of articles on breast as compared
      to other cancers. Latent themes included: an emphasis on fear of cancer in that:
      (1) cancer and fear are frequently conflated; cancer is said to grow outside of
      awareness; cancer is portrayed as (almost) inevitable; cancer is associated with
      normal experiences; early detection is associated with diagnosis; and scary
      statistics are emphasized; (2) contradictions and confusion exist within and
      between articles; and (3) metaphors of war and battle are used frequently. The
      paper concludes with a discussion of the implications of the linking of fear with
      cancer in the context of medicine as the solution.

PMID- 16431005
TI  - Health disparities between racial groups in South Africa: a decomposition
      analysis.
AB  - This article explores the sources of self-rated health status inequalities among
      South Africans. We propose a decomposition of observed health disparities between
      racial groups using a procedure based on an extended version of Oaxaca-Blinder
      decomposition methods which addresses explicitly the specificities associated
      with the analysis of subjective measures. This method allows for a decompositions
      of differences in self-rated health status between races and isolates what may be
      due to observed socioeconomic inequality between racial groups, i.e. an "indirect
      racial effect" (Whites and Africans with different socio-economical
      characteristics have different health), from what could be due to unexplained
      racial differences, i.e. a "direct racial effect" (Whites and Africans with
      similar socio-economical characteristics have different health). Unsurprisingly,
      we find a strong indirect racial effect in favor of Whites. However, our analysis
      tends to show that the issue of direct racial discrimination on health is more
      complex and closely linked with that of economical inequality and discrimination.
      Our results thus stress the necessity not only to open access for Africans to the
      more sophisticated sector of health care but also to provide them with the
      economical opportunity to use it.

PMID- 16431006
TI  - The best experts: the narratives of those who have a genetic condition.
AB  - In recent years, there have been growing expectations about the future benefits
      deriving from the uptake of genetics knowledge in healthcare. At the same time,
      there have been increasing calls to make greater use of patient expertise in
      treatment. However, relatively little is known about the experiences, needs and
      expertise of those who currently have a genetic condition. Drawing on the
      findings from an Australian study involving 21 semi-structured interviews with
      members of support groups which represent those with various genetic conditions
      (cystic fibrosis, haemochromatosis, haemophilia, and thalassaemia) this article
      discusses how individuals learn about, live with and manage their condition, and
      assesses the extent to which their experiences differ from those with other
      chronic illness conditions. It argues that while the experiences of individuals
      who have a genetic condition would appear to be similar in many respects to those
      with other chronic illnesses, they tend to encounter particular challenges in
      managing their condition due to its inheritable nature.

PMID- 16431007
TI  - Regional cerebral blood flow changes in a patient with delusional parasitosis
      before and after successful treatment with risperidone: a case report.
AB  - The pathophysiology and appropriate pharmacological interventions for delusional
      parasitosis (DP) remain unknown. Here, we present a case of DP following brain
      infarction of the right temporoparietal region. Pharmacotherapy with risperidone
      resulted in a dramatic therapeutic response over a short period. In a sequential
      N-isopropyl-p-[(123)I]-iodoamphetamine single photon emission computed tomography
      ([(123)I]-IMP SPECT) study, post-treatment SPECT images revealed a marked
      increase of rCBF in the large areas including the bilateral frontal and left
      temporoparietal regions, the right parietal operculum and the bilateral basal
      ganglia, in contrast to pre-treatment SPECT images showing a global decrease of
      rCBF. Our clinical outcome suggests the efficacy and safety of risperidone for
      treatment of DP and that both dopaminergic and serotonergic dysfunction may play
      a role in DP. Our sequential SPECT findings suggest that psychiatric improvement
      of DP is associated with increased rCBF.

PMID- 16431008
TI  - Relapse during a 6-month continuation treatment with fluvoxamine in an Italian
      population: the role of clinical, psychosocial and genetic variables.
AB  - The efficacy of SSRIs in relapse prevention in major depression has been
      extensively demonstrated. Considering published data, the relapse rate during a
      psychopharmacological continuation treatment ranges from 10% to 30%. Since the
      reasons of depressive relapses could be heterogeneous, we have tested the effect
      of clinical, psychosocial and genetic variables in sustained remission from an
      index depressive episode during continuation treatment with fluvoxamine over a 6
      month follow-up period. 101 patients maintained the same full dosage treatment
      after remission from a depressive episode efficaciously treated with fluvoxamine.
      During the follow-up period, they were clinical assessed monthly by an
      experienced psychiatrist and SASS was administered, to assess their psychosocial
      adjustment. From a genetical point of view, SERTPR and CLOCK polymorphisms were
      analyzed for each patients, using PCR-based techniques. At the end of follow-up
      period, the 57.4% of the patients maintained remission during fluvoxamine
      continuation treatment; the 8.9% relapsed within the first 2 months of
      continuation; the 7.9% switched and the 25.8% dropped-out for poor compliance.
      Relapsed subjects presented a significantly longer mean duration of the index
      depressive episode than non-relapsed subjects and a subjective poor social
      adjustment than non-relapsed also in the euthymia period. None of the analyzed
      polymorphisms significantly appear to influence the outcome of the whole sample.
      The present data confirm that patients with severe depression and a long duration
      of the episode have a major risk of psychosocial disability. These patients could
      need a different psychopharmacological strategies and peculiar psychological
      intervention.

PMID- 16431009
TI  - Performance of a new laser fluorescence device for the detection of occlusal
      caries in vitro.
AB  - The new device DIAGNOdent pen based on red laser light induced fluorescence was
      introduced for the detection of approximal and occlusal caries. The aim of this
      study was to test its performance on occlusal surfaces. The new device comes with
      two different sapphire fibre tips: a cylindrical tip and a conical tip. The two
      new sapphire fibre tips were used and compared with the tip currently available
      with DIAGNOdent (DD). METHODS: The teeth were selected from a pool of extracted
      permanent human molars, which were stored frozen at -20 degrees C, until use.
      Prior to being measured the teeth were defrosted and cleaned. One hundred and
      nineteen teeth were selected and measured with the old tip and with the two new
      tips of the new device by two independent assessments. The teeth were
      histologically prepared and assessed for caries extension. RESULTS: Specificity
      values for D(1), D(2) and D(3) ranged between 0.69 and 0.89, sensitivity between
      0.78 and 0.96. There were no statistically significant differences obtained
      between the two tips of the new and the one tip of the old device (p>0.05). Intra
      examiner reliability with kappa values of >0.83 was high. CONCLUSIONS: In this
      study, the new laser fluorescence device performed on occlusal surfaces as well
      as the available device.

PMID- 16431010
TI  - A potyvirus-based gene vector allows producing active human S-COMT and animal
      GFP, but not human sorcin, in vector-infected plants.
AB  - Potato virus A (PVA), a potyvirus with a (+)ssRNA genome translated to a large
      polyprotein, was engineered and used as a gene vector for expression of
      heterologous proteins in plants. Foreign genes including jellyfish GFP (Aequorea
      victoria) encoding the green fluorescent protein (GFP, 27 kDa) and the genes of
      human origin (Homo sapiens) encoding a soluble resistance-related calcium-binding
      protein (sorcin, 22 kDa) and the catechol-O-methyltransferase (S-COMT; 25 kDa)
      were cloned between the cistrons for the viral replicase and coat protein (CP).
      The inserts caused no adverse effects on viral infectivity and virulence, and the
      inserted sequences remained intact in progeny viruses in the systemically
      infected leaves. The heterologous proteins were released from the viral
      polyprotein following cleavage by the main viral proteinase, NIa, at engineered
      proteolytic processing sites flanking the insert. Active GFP, as indicated by
      green fluorescence, and S-COMT with high levels of enzymatic activity were
      produced. In contrast, no sorcin was detected despite the expected equimolar
      amounts of the foreign and viral proteins being expressed as a polyprotein. These
      data reveal inherent differences between heterologous proteins in their
      suitability for production in plants.

PMID- 16431011
TI  - Integrated monitoring of fetal growth restriction by computerized
      cardiotocography and Doppler flow velocimetry.
AB  - OBJECTIVE: To investigate the correlations between Doppler flow velocimetry and
      computerized cardiotocography (cCTG) in fetal growth restriction. STUDY DESIGN:
      Fifty growth-restricted foetuses with abdominal circumference below the 10th
      percentile and no major abnormalities were studied. A total of 186 cCTG tracings
      (at least two per patient) analysed using the HP2CTG system were compared with
      the corresponding umbilical artery pulsatility index (PI), the PI ratio of
      umbilical artery to middle cerebral artery, and the ductus venosus
      systolic/atrial ratio. RESULTS: Worsening in umbilical artery Doppler velocimetry
      parameters was associated with a significant reduction of short- and long-term
      variability indices and accelerations. When end-diastolic umbilical artery flow
      was preserved, a reversed ratio between umbilical artery and middle cerebral
      artery PIs was not correlated with a worsening of cCTG parameters; in the
      presence of umbilical artery absent or reversed flow, ductus venosus Doppler
      velocimetry abnormalities were correlated with a significant reduction of
      variability. When end-diastolic umbilical artery flow was preserved, there was a
      progressive increase in variability indices and accelerations with advancing
      gestational age. In the more compromised fetuses this "maturation" process of
      cCTG patterns was not found. CONCLUSION: There is a strict correlation between
      Doppler velocimetry abnormalities and cCTG parameter deterioration, in particular
      between ductus venosus and variability.

PMID- 16431012
TI  - Natural history and treatment of bone complications in prostate cancer.
AB  - Bone metastases are highly prevalent in patients with prostate cancer, and they
      commonly present a therapeutic challenge. The natural history of prostatic bone
      metastases is characterized by skeletal morbidity, often producing distressing
      symptoms for individual patients and reducing patient autonomy and mobility.
      These bone metastases are usually radiologically osteoblastic, but there is also
      a strong osteolytic component as evidenced by marked increases in bone resorption
      markers. Malignant bone lesions can reduce the structural integrity of the
      skeleton, resulting in skeletal complications such as pathologic fracture, spinal
      cord compression, and severe bone pain, which adversely affect quality of life.
      Preclinical and clinical studies have provided insight into the pathophysiology
      of malignant bone disease from prostate cancer and suggest that bone-directed
      therapies, including radionuclides, endothelin-1 antagonists, and
      bisphosphonates, may provide both palliative and therapeutic benefits. Clinical
      investigations with these agents are underway in patients with prostate cancer to
      gain insight into the pathophysiology of bone metastases and to evaluate the role
      of bone-specific therapies in treating and preventing bone metastases.

PMID- 16431013
TI  - Can phosphodiesterase type 5 inhibitors cure erectile dysfunction?
AB  - INTRODUCTION AND OBJECTIVES: To systematically analyze and review the available
      evidence about the potential role of chronic administration of phosphodiesterase
      type 5 (PDE-5) inhibitors for the cure of erectile dysfunction (ED) based on
      clinical and basic science data. METHODS: Analysis of published full-length
      papers that were identified with Medline and Cancerlit from January 1993 to
      September 2005. Abstracts published in the journals European Urology, the Journal
      of Urology, the International Journal of Impotence Research, and the Journal of
      Sexual Medicine as official proceedings of internationally known scientific
      societies held in the same time period were also assessed. RESULTS: Chronic
      administration of PDE-5 inhibitors have reportedly been associated with increased
      persistent vascular and endothelial function--which represents a key factor in
      maintaining vascular tone and inducing vasodilation--by increasing the level of
      endothelial cGMP generated by activation of endothelial nitric oxide. Clinical
      studies have revealed a potential protective role of these compounds on
      endothelial function in short- and long-term assessments. Several studies based
      on animal models have provided direct experimental support for the role of PDE-5
      inhibitors in improving the structure and function of the cavernosal tissue and
      have suggested potential molecular mechanisms involved. CONCLUSIONS: Although
      evidence increasingly supports the potential role of chronic administration of
      PDE-5 inhibitors for improving erectile function in patients affected by ED, long
      term data are lacking. However, data available from animal models support the
      evidence of potential benefits induced on endothelial function by chronic
      exposure to PDE-5 inhibitors.

PMID- 16431014
TI  - Analysis of codon usage pattern in the radioresistant bacterium Deinococcus
      radiodurans.
AB  - The main factors shaping codon usage bias in the Deinococcus radiodurans genome
      were reported. Correspondence analysis (COA) was carried out to analyze
      synonymous codon usage bias. The results showed that the main trend was strongly
      correlated with gene expression level assessed by the "Codon Adaptation Index"
      (CAI) values, a result that was confirmed by the distribution of genes along the
      first axis. The results of correlation analysis, variance analysis and neutrality
      plot indicated that gene nucleotide composition was clearly contributed to codon
      bias. CDS length was also key factor in dictating codon usage variation. A
      general tendency of more biased codon usage of genes with longer CDS length to
      higher expression level was found. Further, the hydrophobicity of each protein
      also played a role in shaping codon usage in this organism, which could be
      confirmed by the significant correlation between the positions of genes placed on
      the first axis and the hydrophobicity values (r=-0.100, P<0.01). In summary, gene
      expression level played a crucial role, nucleotide mutational bias, CDS length
      and the hydrophobicity of each protein just in a minor way in shaping the codon
      usage pattern of D. radiodurans. Notably, 19 codons firstly defined as "optimal
      codons" may provide useful clues for molecular genetic engineering and
      evolutionary studying.

PMID- 16431015
TI  - Human epididymal secretome and proteome.
AB  - The proteins that are neosynthesized and secreted in the different regions of the
      human epididymis were determined by in vitro biosynthesis of epididymal tubules,
      and the luminal proteins were collected by microperfusion of each tubule. The
      preparations were analyzed by two-dimensional gel electrophoresis and the
      proteins were identified by mass spectrometry. Some of the major proteins
      identified corresponded to serum compounds such as albumin, transferrin and alpha
      1-antitrypsin. The other proteins identified included lactotransferrin,
      clusterin, PEBP, NCP2/CTP/HE1, HE3, Crisp, actin, calmodulin, E12, PGDS, l
      lactate dehydrogenase, malate dehydrogenase, carbonic anhydrase, triose phosphate
      isomerase, glutamyltransferase, glutathione S-transferase P, thioredoxin
      peroxidase, superoxide dismutase, cathepsin D and cystatin. Epididymal activity
      is highly regionalized in most species. However, in this study in humans, there
      were only minor changes in the major proteins secreted. It is suggested that this
      specificity might be related to the difference between species in the location of
      the epididymis where sperm become fertile.

PMID- 16431016
TI  - Active site variability of type 1 11beta-hydroxysteroid dehydrogenase revealed by
      selective inhibitors and cross-species comparisons.
AB  - The NADPH-dependent enzyme type 1 11beta-hydroxysteroid dehydrogenase (11beta
      HSD1) activates in a tissue-specific manner circulating pro-glucocorticoid
      hormones (cortisone in humans) to the 11beta-OH ligand (cortisol in humans),
      which is able to bind to its cognate receptor and regulate gene transcription.
      Modulation of this pre-receptor activation mechanism by selective enzyme
      inhibitors is a desirable goal in the treatment of insulin resistance and related
      metabolic disorders. Like most other hydroxysteroid dehydrogenases 11beta-HSD1
      belongs to the evolutionarily conserved enzyme superfamily of short-chain
      dehydrogenases/reductases (SDR). The enzyme is anchored within the endoplasmic
      reticulum through an N-terminal transmembrane domain. In this study we aimed to
      characterize the active site of mammalian 11beta-HSD1 by determining primary
      structures from several mammalian lines (cat, hamster, cynomolgus, chimpanzee,
      dog) thus increasing substantially available sequence information, and allowing
      us to determine highly variable and constant parts within the primary structure.
      These regions were mapped to the recently determined three-dimensional structure
      and are mostly found around the substrate binding site. Furthermore we performed
      inhibition studies by using different series of inhibitors, comprising 11beta
      HSD1 selective arylsulfonamidothiazoles and the unselective steroid-based
      compound carbenoxolone. The different arylsulfonamidothiazoles display distinct
      inhibition profiles versus the mammalian species tested, with several tight
      binding inhibitors for the human enzyme (Ki approximately 50 nM), intermediate
      for mouse, and weak or not binding inhibitors for rat and guinea pig (Ki>3
      microM). Analysis of the inhibition mode reveals that the tight binding inhibitor
      BVT.528 is a competitive inhibitor for the human form, whereas the related
      compound BVT.2733 displays a mixed-type inhibition pattern versus the mouse
      enzyme. Taken together, this structure-activity study provides increased insight
      into active site complexity and catalytic mechanism of 11beta-HSD1, useful for
      further inhibitor design.

PMID- 16431017
TI  - Regulation of junction dynamics in the testis--transcriptional and post
      translational regulations of cell junction proteins.
AB  - Cell junctions are the sites at which cells attach to the neighboring cells. They
      do not only maintain tissue integrity, their turnover also plays a crucial role
      in cell development and morphogenesis. In the testis, tight junctions and
      adherens junctions are dynamically remodeled to allow the movement of post
      meiotic germ cells across the seminiferous epithelium and the timely release of
      spermatids into the tubular lumen. There is growing evidence that this dynamic
      remodeling of cell junctions is mediated by several mechanisms at the
      transcriptional and post-translational levels. This review summarizes what is
      known about the transcriptional regulation, ubiquitination and endocytosis that
      are involved in modulating junction dynamics in epithelial cells. It also
      highlights the recent findings on the regulation of junction dynamics in the
      testis and the specific areas that require further research for a thorough
      understanding of the role of junction remodeling in spermatogenesis.
      Understanding the junction dynamics in the seminiferous epithelium may unfold new
      targets for non-hormonal male contraceptive development.

PMID- 16431018
TI  - Studies on accumulation of uranium by fungus Lentinus sajor-caju.
AB  - The untreated, heat- and alkali-treated Lentinus sajor-caju mycelia were used for
      the recovery of uranium from aqueous solutions. The effect of pH, temperature,
      initial concentration of UO(2)(2+) ions and contact time parameters were
      investigated in a batch system. The particles sizes of the fungal mycelia were
      ranging from 100 to 200 microm. Biosorption equilibriums were established in
      about 30 min and the correlation regression coefficients show that the adsorption
      process can be well defined by the Freundlich equation. The alkali treated form
      had a high biosorption capacity (378 mg/g) than those of the untreated (268 mg/g)
      and heat-treated fungal mycelia (342 mg/g). Optimum biosorption was observed at
      pH 4.5 for all the tested fungal preparations and was independent of temperature
      (5-35 degrees C). In addition, the polarity and surface energy of the fungal
      biomass film preparations were determined by contact angle measurement. The
      fungal biomass could be regenerated using 10mM sodium carbonate, with up to 93%
      recovery. The biosorbents were used in six biosorption-desorption cycles and no
      considerable loss in the biosorption capacity was observed.

PMID- 16431019
TI  - Removal of selected pollutants from aqueous media by hardwood mulch.
AB  - Generic hardwood mulch, usually used for landscaping, was utilized to remove
      several selected pollutants (heavy metals and toxic organic compounds) typically
      found in urban stormwater (SW) runoff. The hardwood mulch sorbed all the selected
      pollutants from a spiked stormwater mixture, including copper (Cu(2+)), cadmium
      (Cd(2+)), chromium (Cr(6+)), lead (Pb(2+)), zinc (Zn(2+)), 1,3 dichlorobenzene
      (DCB), naphthalene (NP), fluoranthene (FA), butylbenzylphthalate (BBP), and
      benzo(a)pyrene (B[a]P). Masses of the pollutants sorbed depended upon the
      pollutant species, contact time, and initial concentration which varied from 20
      to 100%. Sorption rates of the metals, in general, were more rapid than those of
      the organics; however, mass removals (percent) of the organics, in contrast to
      those of the metals, were independent of their initial concentrations. With the
      exception of Cd, percentages (weight) of the metals removed declined as their
      initial concentrations decreased. None of the sorbed pollutants desorbed to any
      significant extent upon extended washing with water. It is quite feasible that in
      the presence of mulch the uptake of these pollutants by the aquatic species will
      be reduced significantly.

PMID- 16431020
TI  - Assessment of the multi-compound non-equilibrium dissolution behaviour of a coal
      tar containing PAHs and phenols into water.
AB  - Herein, an experimental study coupled with a model in order to assess the non
      equilibrium and multi-compound dissolution behaviour of a coal tar containing
      PAHs and phenols into water, is presented. For this aim, two experimental studies
      has been carried out: (1) coal tar-water partition equilibrium and (2)
      dissolution dynamics of coal tar under controlled hydrodynamic conditions in
      percolation columns packed with glass beads. The dissolution amount of the three
      target constituents (i.e. phenol, naphthalene and phenanthrene) was monitored by
      UV detection. The dissolution behaviour was modelled using a predictive fraction
      approach. The partition coefficients have been estimated from experimental data
      and the obtained results show that the partition coefficient of each constituent
      between the aqueous phase and the tar depends on the activities of the
      constituent in both phases and cannot be estimated only from the solubility of
      the pure compound in water. The non-equilibrium dissolution model was
      established, applied for the experimental conditions and validated for three
      target compounds adjusting the effective interfacial area between tar and water.
      This parameter is specific of the experimental set-up. The global behaviour of
      coal tar has been modelled taking into account four categories of compounds
      according to their water solubility and volatilities. The mass transfer
      parameters have been estimated using available correlations. The results of this
      paper indicate that a model based on component fractions can be used to assess
      the non-equilibrium dissolution behaviour of a coal tar.

PMID- 16431021
TI  - Multifunctional microsized modified kaolin and its application in wastewater
      treatment.
AB  - The multifunctional microsized ZnO-PO(4)(3-)-modified kaolin of average diameter
      about 500nm with the composition Na(2)O:ZnO:Na(3)PO(4):SiO(2):Al(2)O(3)=2.5
      8.5:0.04-0.65:0.8-4.5:1.5-2.5:1 (molar ratio) were firstly synthesized from ZnO,
      Na(3)PO(4), NaOH and kaolin and characterized by standard techniques, its
      application in oilfield produced wastewater purification was also studied. It was
      found that the physical properties of ZnO-PO(4)(3-)-modified kaolin such as
      specific surface area, porous volume and pore diameter increased independently
      compared to the starting kaolin. It was also found that the prepared kaolin has
      multifunctional properties to decrease COD and BOD value, remove scaling ion
      (Fe(n+), Ca(2+) and Mg(2+)), improve MF, decrease bacteria and inhibit corrosion
      and can be used effectively in oilfield wastewater purification.

PMID- 16431022
TI  - Treatment of pulp and paper mill wastewater by polyacrylamide (PAM) in polymer
      induced flocculation.
AB  - The flocculation performances of nine cationic and anionic polyacrylamides with
      different molecular weights and different charge densities in the treatment of
      pulp and paper mill wastewater have been studied. The experiments were carried
      out in jar tests with the polyacrylamide dosages range of 0.5-15 mg l(-1), rapid
      mixing at 200 rpm for 2 min, followed by slow mixing at 40 rpm for 15 min and
      settling time of 30 min. The effectiveness of the polyacrylamides was measured
      based on the reduction of turbidity, the removal of total suspended solids (TSS)
      and the reduction of chemical oxygen demand (COD). Cationic polyacrlyamide
      Organopol 5415 with very high molecular weight and low charge density is found to
      give the highest flocculation efficiency in the treatment of the paper mill
      wastewater. It can achieve 95% of turbidity reduction, 98% of TSS removal, 93% of
      COD reduction and sludge volume index (SVI) of 14 ml g(-1) at the optimum dosage
      of 5 mg l(-1). SVI values of less than 70 m lg(-1) are found for all
      polyacrylamide at their respective optimum dosage. Based on the cost evaluation,
      the use of the polyacrylamides is economically feasible to treat the pulp and
      paper mill wastewaters. This result suggests that single-polymer system can be
      used alone in the coagulation-flocculation process due to the efficiency of the
      polyacrylamide. Sedimentation of the sludge by gravity thickening with settling
      time of 30 min is possible based on the settling characteristics of the sludge
      produced by Organopol 5415 that can achieve 91% water recovery and 99% TSS
      removal after 30 min settling.

PMID- 16431023
TI  - Long-term enhanced desynchronization of the alpha rhythm following tetanic
      stimulation of human visual cortex.
AB  - It had been shown previously that a photic tetanus induces LTP-like changes in
      the visual cortex, as indexed by an enhancement of the N1b component of the
      visual evoked potential, recorded non-invasively by electroencephalography. This
      potentiation was shown to last over 1 h. In the present study, the effect of a
      photic tetanus on oscillatory activity is investigated. EEGs were collected from
      eight healthy subjects in three conditions while visual checkerboards were
      displayed. Following baseline presentations in two conditions a lateralized
      visual tetanus was given, either to the left or right visual field, and in a
      third condition no tetanus was given. This was followed by a return to baseline
      presentations, both immediately after the tetanus/control block, and 1 h later.
      Enhanced event-related desynchronization (ERD) of the alpha rhythm lasting 1 h
      was seen following the photic tetanus over occipital electrodes. Because ERD of
      the alpha rhythm is thought to represent active cortex, these results suggest
      that the visual tetanus induces long-lasting cortical changes, with stronger
      neuronal assemblies and increased neuronal output.

PMID- 16431025
TI  - Sweet secret of the multicellular life.

PMID- 16431026
TI  - Intracellular conformational alterations of mutant SOD1 and the implications for
      fALS-associated SOD1 mutant induced motor neuron cell death.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
      by the selective death of motor neurons. Approximately 10% of ALS cases are
      familial (fALS) and about 25% of fALS patients inherit autosomal dominant
      mutations in the gene encoding copper-zinc superoxide dismutase (SOD1). Over 90
      different SOD1 mutations have been identified in fALS patients. It has been
      established that the ALS-linked SOD1 mutations provoke a new toxic function, the
      nature of which remains unclear. In vitro studies using various biophysical
      techniques have demonstrated that the SOD1 mutants share a reduced conformational
      stability. However, conformational alterations of the ALS mutants have not been
      directly demonstrated in vivo. We employed an SOD1-GFP fusion protein system in
      this study to monitor the intracellular protein conformation. We demonstrate that
      the ALS-linked SOD1 mutants adopt different conformations from the wild-type (WT)
      protein in living cells. Moreover, the conformational alterations of mutant SOD1
      render the mutants susceptible to the formation of high-molecular-weight
      complexes prior to the appearance of detergent-resistant aggregates. Finally, we
      show that the motor neuron-like cells expressing mutant SOD1 are more susceptible
      to H2O2 induced cell death compared to the cells expressing WT SOD1. This study
      provides direct evidence of in vivo conformational differences between WT and
      mutant SOD1. In addition, the SOD1-GFP system can be exploited in future studies
      to investigate how conformational alterations of mutant SOD1 lead to protein
      aggregation and to study the potential toxicity of such aggregates in familial
      ALS.

PMID- 16431024
TI  - CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.
AB  - It was reported in 1995 that a large Danish family with familial frontotemporal
      dementia (FTD) was linked to the pericentromeric region of chromosome 3. It has
      since been claimed that a mutation in the splice acceptor site of exon 6 of
      CHMP2B is the pathogenic variant in this family. In order to determine whether
      CHMP2B mutations are a common cause of disease in patients with frontotemporal
      lobar degeneration (FTLD) we sequenced all exons and flanking regions of CHMP2B
      in 141 familial FTLD probands from the USA and UK. We failed to find a single
      pathogenic variant in any case. Polymorphisms were detected but were present in
      control samples. We conclude that mutations in CHMP2B are a rare cause of
      familial FTLD and may be specific to the Danish pedigree.

PMID- 16431027
TI  - Habituation to repeated restraint stress is associated with lack of stress
      induced c-fos expression in primary sensory processing areas of the rat brain.
AB  - Rats repeatedly exposed to restraint show a reduced hypothalamic-pituitary
      adrenal axis response upon restraint re-exposure. This hypothalamic-pituitary
      adrenal axis response habituation to restraint does not generalize to other novel
      stressors and is associated with a decrease in stress-induced c-fos expression in
      a number of stress-reactive brain regions. We examined whether habituation to
      repeated restraint is also associated with adaptation of immediate early gene
      expression in brain regions that process and relay primary sensory information.
      These brain regions may not be expected to show gene expression adaptation to
      repeated restraint because of their necessary role in experience discrimination.
      Rats were divided into a repeated restraint group (five 1-hour daily restraint
      sessions) and an unstressed group (restraint naive). On the sixth day rats from
      each group were either killed with no additional stress experience or at 15, 30
      or 60 min during restraint. Immediate early gene expression (corticotrophin
      releasing hormone heteronuclear RNA, c-fos mRNA, zif268 mRNA) was determined by
      in situ hybridization. A reduction in stress-induced hypothalamic-pituitary
      adrenal axis hormone secretion (plasma corticosterone and adrenocorticotropic
      hormone) and immediate early gene expression levels in the paraventricular
      nucleus of the hypothalamus, the lateral septum and the orbital cortex was
      observed in repeated restraint as compared with restraint naive animals. This
      reduction was already evident at 15 min of restraint. Unexpectedly, we also found
      in repeated restraint rats a reduction in restraint-induced c-fos expression in
      primary sensory-processing brain areas (primary somatosensory cortex, and
      ventroposteriomedial and dorsolateral geniculate nuclei of thalamus). The overall
      levels of hippocampal mineralocorticoid receptor heteronuclear RNA or
      glucocorticoid receptor mRNA were not decreased by repeated restraint, as may
      occur in response to severe chronic stress. We propose that repeated restraint
      leads to a systems-level adaptation whereby re-exposure to restraint elicits a
      rapid inhibitory modulation of primary sensory processing (i.e. sensory gating),
      thereby producing a widespread attenuation of the neural response to restraint.

PMID- 16431028
TI  - P2 receptor-stimulation influences axonal outgrowth in the developing hippocampus
      in vitro.
AB  - Extracellular ATP might act as a trophic factor on growing axons during
      development of the CNS via P2 receptors. In the present study the postnatal
      presence of selected P2 receptor subtypes was analyzed and their putative trophic
      capacity in entorhino-hippocampal slice co-cultures of mouse brain was tested.
      The effect of the P2 receptor ligands 2-methylthioadenosine-5'-triphosphate
      (P2X/Y receptor agonist) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic
      acid (P2X/Y receptor antagonist) on axonal growth and fiber density of biocytin
      labeled hippocampal projections was compared both with untreated cultures and
      with cultures treated with artificial cerebrospinal fluid. After 10 days in
      vitro, double immunofluorescence labeling revealed the expression of P2X(1),
      P2X(2), P2X(4) as well as P2Y(1) and P2Y(2) receptors in the examined regions of
      entorhinal fiber termination. Further, quantitative analysis of identified
      biocytin-traced entorhinal fibers showed a significant increase in fiber density
      in the dentate gyrus after incubation of the slices with the P2 receptor agonist
      2-methylthioadenosine-5'-triphosphate. This neurite outgrowth promoting effect
      was completely abolished by the P2 receptor antagonist pyridoxalphosphate-6
      azophenyl-2',4'-disulphonic acid. Our in vitro data indicate that ATP via its P2X
      and P2Y receptors can shape hippocampal connectivity during development.

PMID- 16431029
TI  - Increased polysialic acid neural cell adhesion molecule expression in human
      hippocampus of heroin addicts.
AB  - Chronic exposure to heroin is known to cause cognitive deficits. However, little
      is known about the underlying molecular mechanisms. It has been suggested that
      opiate-induced neurotoxicity as well as impaired plasticity and regeneration may
      be relevant. One of the target regions where regeneration still can be observed
      in the adult brain is the hippocampus. Since polysialic acid neural cell adhesion
      molecule is regarded as one of the key players involved in plasticity and
      regeneration of neural tissue, we analyzed polysialic acid neural cell adhesion
      molecule expression in the fascia dentate hilus of the human hippocampus of 29
      lethally intoxicated heroin addicts and matched controls. Immunohistochemistry
      with an antibody directed against polysialic acid neural cell adhesion molecule
      revealed its expression in differently sized cells which could be identified as
      neurons and glial cells. We observed an increase in the percentage of polysialic
      acid neural cell adhesion molecule positive neurons in hippocampal hilus of
      heroin addicts compared with controls (P = 0.001).Interestingly, we also observed
      polysialic acid neural cell adhesion molecule expression in glial cells as
      evidenced by double immunofluorescence with glial fibrillary acidic protein and
      polysialic acid neural cell adhesion molecule using confocal laser scanning
      microscopy. The fraction of polysialic acid neural cell adhesion molecule
      positive glial cells was also higher in heroin addicts compared with controls (P
      = 0.009). In addition, within the group of addicts morphine blood concentrations
      showed a positive correlation with the percentage of polysialic acid neural cell
      adhesion molecule positive neurons (P = 0.04; r = 0.547). In conclusion, we
      observed an increase in polysialic acid neural cell adhesion molecule positive
      neurons and glial cells in hippocampi of heroin addicts. This might reflect an
      attempt to repair cell damage due to heroin exposure.

PMID- 16431030
TI  - Improvement in measures of psychological distress amongst amphetamine misusers
      treated with brief cognitive-behavioural therapy (CBT).
AB  - This trial of cognitive-behavioural therapy (CBT) based amphetamine abstinence
      program (n=507) focused on refusal self-efficacy, improved coping, improved
      problem solving and planning for relapse prevention. Measures included the
      Severity of Dependence Scale (SDS), the General Health Questionnaire-28 (GHQ-28)
      and Amphetamine Refusal Self-Efficacy. Psychiatric case identification (caseness)
      across the four GHQ-28 sub-scales was compared with Australian normative data.
      Almost 90% were amphetamine-dependent (SDS 8.15+/-3.17). Pre-treatment, all GHQ
      28 sub-scale measures were below reported Australian population values. Caseness
      was substantially higher than Australian normative values {Somatic Symptoms
      (52.3%), Anxiety (68%), Social Dysfunction (46.5%) and Depression (33.7%)}. One
      hundred and sixty-eight subjects (33%) completed and reported program abstinence.
      Program completers reported improvement across all GHQ-28 sub-scales {Somatic
      Symptoms (p<0.001), Anxiety (p<0.001), Social Dysfunction (p<0.001) and
      Depression (p<0.001)}. They also reported improvement in amphetamine refusal self
      efficacy (p<0.001). Improvement remained significant following intention-to-treat
      analyses, imputing baseline data for subjects that withdrew from the program. The
      GHQ-28 sub-scales, Amphetamine Refusal Self-Efficacy Questionnaire and the SDS
      successfully predicted treatment compliance through a discriminant analysis
      function (p<.001).

PMID- 16431031
TI  - Postpartum return to smoking: identifying different groups to tailor
      interventions.
AB  - OBJECTIVE: (a) To describe a population-based sample of women postpartum who
      smoked before pregnancy on grounds of the perceived advantages and disadvantages
      of nonsmoking and the self-efficacy not to smoke. (b) To identify grouping
      characteristics that can differentiate among those women. This could lead to the
      development of intervention strategies that are of different efficacy depending
      on the cluster the woman is member of. SAMPLE: A population-based sample of 317
      women who had smoked at the beginning of pregnancy and who were smoke-free at the
      time of giving birth. DATA: Data about the acquisition stages of change to
      restart smoking, the perceived advantages of nonsmoking and the self-efficacy to
      remain smoke free on grounds of the Transtheoretical Model of Behavior Change was
      assessed. Smoking status was assessed 12 months later. STATISTICAL ANALYSIS: A
      cluster analysis was used to identify different groups; a logistic regression was
      calculated to assure the external validity of the clusters identified. RESULTS:
      The acquisition stages of change do not fit the situation of nonsmoking women
      postpartum in Germany, but four different clusters of ex-smoking women postpartum
      were identified on grounds of the other TTM-constructs. These are: the protected,
      the high risk, the premature and the ambivalent group. The clusters are
      associated with relapse after 12 months, none of the other variables controlled
      for was statistically significant. CONCLUSIONS: The TTM contributes to a better
      understanding of nonsmoking women postpartum. Further studies have to replicate
      the clusters found and have to find whether interventions tailored to these
      clusters are more effective in preventing relapse than other interventions.

PMID- 16431032
TI  - Tumor-causing plant bacteria may infect animals.

PMID- 16431033
TI  - Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl
      may cause sensitization and subsequent opiate addiction among anesthesiologists
      and surgeons.
AB  - We hypothesize that aerosolization of anesthetics administered intravenously to
      patients in the operating room may be an unintended source of exposure to
      physicians. This may lead to inadvertent sensitization, which is associated with
      an increased risk for developing addiction. This may contribute to the over
      representation of certain specialties among physicians with addiction. We
      retrospectively reviewed the de-identified demographic information of all
      licensed physicians treated for substance abuse in the State of Florida since
      1980, to determine if medical specialty was associated with addiction in this
      group of individuals. Then, to identify the potential for exposure, two mass
      spectrometry assays were developed to detect two intravenously administered
      drugs, fentanyl and propofol, in air. Since 1980, 7.6% of licensed Florida
      physicians underwent treatment for addiction. Addiction in anesthesiologists was
      higher than expected. Opiate abuse was greater in anesthesiologists and surgeons
      compared to other specialties. Aerosolized fentanyl was detected in the air of
      the cardiothoracic operating room, in patients' expiratory circuits, and in the
      headspace above sharps boxes, but not in adjoining hallways. Aerosolized propofol
      was detected in the expirations of a patient undergoing transurethral
      prostatectomy. While access and stress may place anesthesiologists and surgeons
      at greater risk for substance abuse, an additional risk factor may be unintended
      occupational exposure to addictive drugs. This report provides preliminary
      evidence of detection of aerosolized intravenous anesthetics using two newly
      developed analytical methods. We conclude that the potential exists for chronic
      exposure to low levels of airborne intravenously administered drugs. Further
      studies are under way to determine the significance of this exposure.

PMID- 16431034
TI  - Crohn's disease leading to bowel cancer may be avoided by consumption of soya
      isoflavones: adjunct-chemotherapy with oxaliplatin.
AB  - Crohn's disease (inflammatory bowel syndrome) is caused by gut exposure to
      harmful reactive oxygen species (ROS) derived from oxygen, such as the superoxide
      anion ((.)O(2)'), the hydroxyl radical ((.)OH) or the peroxide anion (O(2)''):
      the superoxide anion is generated by breakdown of oxygen-peroxidised
      phospholipids membranes. Crohn's disease predisposes to bowel cancer in
      susceptible human sub-populations. It may be preventable in these as yet
      unpredictable sub-populations by dietary-based intervention strategies, such as
      the daily consumption of appropriate quantities of soya isoflavones. These
      isoflavonoids are ROS-directed antioxidants, and they include the phytoestrogens,
      daidzin and genistin present in soya foods (consumed also in dietary
      supplements). Oxaliplatin is a platinum-containing Pt(II) organometallic
      therapeutic agent that binds to tumour DNA. Oxaliplatin may provide, therefore, a
      form of chemotherapy for some bowel cancers especially when administered in
      adjunct-chemotherapies that employ inhibitors of proliferation of the tumour
      cell. Such inhibitors include 5-fluorouracil, which prevents the correct
      replication of tumour cell DNA that is an essential prerequisite for bowel tumour
      growth. Furthermore, the therapeutic index for adjunct-chemotherapy with toxic
      inhibitors of DNA replication and expression could potentially be raised
      significantly by an associated dietary regime. This should include
      supplementation daily, per or, with antioxidant isoflavones (or other
      bioflavonoids) in selected cases of unresponsive cancer of the bowel, to possibly
      seek to trigger the pathway of apoptosis (programmed cell death) in the tumour
      cells preferentially.

PMID- 16431035
TI  - Is there a role for atrial peptides in the labyrinthine "disease"?
AB  - The important role of atrial natriuretic peptides (ANP) in regulating blood
      pressure and changing vascular permeability has been widely studied and assessed
      during the last ten years. Considering the characteristics of this mechanism,
      which is responsible for a hypotensive and hypovolemic effect, and the possible
      role of hypotension associated with a default of autoregulatory sympathetic
      reactions in inner ear unexplained disorders, it seems reasonable to hypothesize
      a possible involvement of ANP system in the genesis of such disorders. As a
      matter of fact, the presence of specific receptors for ANP in the inner ear has
      been widely reported in studies concerning both rat and human inner ear, although
      their precise role in the labyrinthine homeostasis has not been satisfactory
      explained until now. Some aspects concerning vascular and fluid regulation of the
      inner ear under different conditions still remain not totally clear, and
      consequently a detailed explanation to the possible mechanism causing inner ear
      disorders of functional origin is lacking; from this point of view, an
      investigation on the serum level of ANP in subjects with labyrinthine affections
      of uncertain origin could be of some utility in contributing to assess the role
      of this system in the inner ear fluid regulation and in the inner ear perfusion
      and to investigate on the possible influence of an abnormal ANP release in some
      kind of inner ear damage.

PMID- 16431036
TI  - A new bicoumarin from the leaves and stems of Triphasia trifolia.
AB  - A new bicoumarin (3) was isolated from the leaves and stems of Triphasia
      trifolia. Its structure was determined by spectral data, in particular two
      dimensional NMR experiments. It appeared that the two coumarinic moieties of 3
      are derivatives of mexoticin (1) and meranzin hydrate (2), which are known
      constituents of the plant.

PMID- 16431037
TI  - Identification of two new members, XPLAC and XTES, of the XK family.
AB  - XK, a putative membrane transporter, is a component of the XK/Kell complex of the
      Kell blood group system. XK's substrate is unknown but absence of the protein, as
      occurs in the McLeod phenotype, is associated with red cell acanthocytosis and
      late onset central nervous system and neuromuscular abnormalities known as the
      McLeod syndrome. We have cloned two cDNAs, XPLAC (GenBank accession no. AY589511)
      and XTES (GenBank accession no. AY989815), which are closely related to XK and
      define them together as the XK family. XPLAC has a 2.9 kb cDNA that encodes 462
      amino acids and XTES has a 1.6 kb cDNA coding 459 amino acids. The predicted
      molecular weights are 53.6 kDa for XPLAC and 53.4 kDa for XTES, which are similar
      to that of XK, which is 50.9 kDa. Unlike XK which is ubiquitously expressed XPLAC
      is expressed mostly in placenta and adrenal gland while XTES is exclusively
      expressed in primate testis. XPLAC has 37% and XTES has 31% amino acid identity
      with XK protein and they are predicted to have a similar topology to XK. XPLAC,
      like XK, has 3 exons and is located on X chromosome at q22.1, while XTES has 4
      exons and is located at 22q11.1. Phylogenetic analysis shows that there are at
      least 5 additional vertebrate genes that are evolutionarily distantly related to
      the XK family. A domain with consensus sequences (ced-8 domain) for the extended
      family is described.

PMID- 16431038
TI  - Distinctive organization of genes for light-harvesting proteins in the
      cryptophyte alga Rhodomonas.
AB  - Cryptophyte algae contain two kinds of light-harvesting protein,
      phycobiliproteins and chlorophyll a,c-binding proteins. The beta subunit of the
      phycobiliprotein phycoerythrin (PE) is encoded in the chloroplast. Genes for the
      other PE polypeptides are located in the nucleus but little is known of their
      organization. We cloned and sequenced six cpeA genes encoding the phycoerythrin
      alpha subunit from a genomic library of the cryptophyte Rhodomonas CS24. Derived
      peptide sequences of the cpeA genes show that alpha subunits occur in at least
      two forms, a longer alpha1 form and a shorter alpha2 form. Remarkably, all six
      cpeA genes occur in divergent pairs encoding one alpha1 and one alpha2 subunit.
      Four cac genes encoding chlorophyll a,c-binding proteins were cloned and
      sequenced and also found to occur in divergent pairs comprising one cac1 and one
      cac2 gene. Inspection of the predicted targeting sequences of the alpha1 and
      alpha2 phycoerythrin polypeptides shows that only the alpha1 polypeptides have a
      thylakoid lumen targeting sequence, corresponding to the TAT pathway. Given the
      previously reported lack of a lumen-targeting sequence on the beta subunit, we
      propose a novel import mechanism in which the entire alpha1alpha2 betabeta
      phycoerythrin complex is assembled in the stroma and transported into the
      thylakoid under the direction of the single targeting sequence on the alpha1
      protein. The FAP motif implicated in plastid targeting in diatoms appears to be
      conserved in this cryptophyte.

PMID- 16431039
TI  - Human and orthologous gene nomenclature.
AB  - Standardised human gene nomenclature is an essential tool for all researchers,
      and applying this nomenclature to orthologous genes in other species greatly
      extends its utility. As more genomes are sequenced and annotated the wealth of
      information in the public domain concerning homologous genes and their products
      increases greatly. Here we review many of the resources currently available for
      identifying orthologs and paralogs, and viewing regions of synteny between
      genomes, and discuss how these can and are being used in the process of
      nomenclature assignment. Whilst synchronised gene naming has been actively
      pursued between human and mouse for many years, and continues apace, it is hoped
      that this nomenclature will eventually be extended to many other comparative
      genomes.

PMID- 16431040
TI  - Changes in antimicrobial susceptibility of Actinobacillus pleuropneumoniae
      isolated from pigs in Spain during the last decade.
AB  - A total of 229 Spanish Actinobacillus pleuropneumoniae isolates recovered from
      diseased pigs with pleuropneumonia from 1997 to 2004 was tested for their
      susceptibility to 11 antimicrobials in a broth microdilution method. All the
      isolates were susceptible to florfenicol and most of them to cephalothin;
      however, a high rate of resistance was observed to tetracycline. A bimodal or
      multimodal distribution of isolates over the MIC range were observed for
      penicillins, tetracycline, trimethoprim, sulfisoxazole and nalidixic acid,
      suggesting the development of acquired resistance. Eight resistance patterns were
      established, and 21.1% of the isolates were resistant to at least two
      antimicrobials. In addition, a considerable increase in the resistance to
      tetracyclines was observed during the last decade in Spain, when compared with
      other A. pleuropneumoniae strains isolated during 1987-1988 (Gutierrez, C.B.,
      Piriz, S., Vadillo, S., Rodriguez Ferri, E.F., 1993. In vitro susceptibility of
      Actinobacillus pleuropneumoniae strains to 42 antimicrobial agents. Am. J. Vet.
      Res. 54, 546-550); this finding was also observed for gentamicin in minor
      percentage.

PMID- 16431041
TI  - Virulence-associated gene profiling of Streptococcus suis isolates by PCR.
AB  - Definition of virulent Streptococcus suis strains is controversial. One
      successful approach for identification of virulent European strains is
      differentiation of capsular serotypes (or the corresponding cps types) and
      subsequent detection of virulence-associated factors, namely the extracellular
      factor (EF, epf), the muramidase-released protein (MRP, mrp) and the hemolysin
      suilysin (SLY, sly). In this work we present a novel multiplex PCR (MP-PCR) and
      an mrp variant PCR for identification and characterization of virulent S. suis
      strains. These new methods were used to identify association of disease with
      particular profiles of virulence-associated genes. The MP-PCR allowed
      identification of S. suis through detection of the housekeeping gene gdh,
      differentiation of four cps types (1, 2, 7 and 9), and detection of epf, mrp, sly
      and arcA (arginine deiminase from S. suis). Furthermore, this study describes the
      first PCR assay for differentiation of at least six mrp variants. Expression of
      the corresponding size variants of MRP was shown for four of the six mrp
      variants, but was undetectable for the two larger mrp variants in the particular
      strains investigated. The results of this study suggest that cps7 strains are
      associated with pneumonia and that variation of mrp is very pronounced among
      these strains. Gene profiles of invasive, pneumonia and carrier S. suis isolates
      by combination of PCR assays allowed differentiation of 24 different genotypes
      among cps1, 2, 7 and 9 strains. Forty-five percent of the invasive S. suis
      diseases investigated in this study were caused by only two of these genotypes,
      namely cps2/mrp+/epf+/sly+ and cps9/mrp(*)/epf-/sly+. Thus, this study
      demonstrates for the first time a uniform profile of the particular virulence
      associated genes for the vast majority of the investigated invasive cps9 strains.

PMID- 16431042
TI  - Early childhood growth and development in rural Guatemala.
AB  - BACKGROUND: Small size at birth and in early childhood has been associated with
      impaired neurodevelopment in studies from developing countries, but few have
      examined associations with growth. AIMS: The objective of this study was to
      assess the relationship between growth and neurodevelopment during early
      childhood (birth-36 months). DESIGN: Multivariate regression models were used to
      analyze the data collected in the course of a study of pregnancy outcomes and
      early childhood growth and development carried out in rural Guatemala in 1991
      1999. Motor and mental development scores were based on the Psychomotor and
      Mental Development Indices, respectively, derived from the administration of an
      adapted version of the Bayley Scales of Infant Development (Second Edition, 1993)
      at 6, 24 and 36 months. Z-scores for height-for-age (HAZ), weight-for-age (WAZ),
      and head circumference-for-age (HCZ) were used as indicators of attained size;
      changes in these Z-scores over time represent growth. RESULTS: Birth size was
      significantly associated with child development at 6 and 24 months. Gains in
      length and weight during the first 24 months were positively associated with
      child development, whereas growth from 24 to 36 months age was not associated
      with child development at 36 months. Motor development was more strongly and
      consistently related to child growth than was mental development. Head
      circumference gain after 6 months was not a significant predictor of child
      development at 24 and 36 months. CONCLUSIONS: Small size at birth and poor
      physical growth during the first 24 months are related to neurodevelopmental
      delays. More evidence from developing countries will help explain the underlying
      mechanisms and identify appropriate interventions to prevent neurodevelopmental
      delay in early childhood.

PMID- 16431043
TI  - Reproductive performance of high growth rate gilts inseminated at an early age.
AB  - The aim of this work was to determine if gilts, which have a high growth rate
      (GR) could be mated earlier without reducing the reproductive performance or
      increasing the culling rate up to the third parity. Gilts of Camborough 22 (C22,
      n=568) breeding were mated and allocated into three groups according to weight
      and age on the insemination day. G1 (n=164)-gilts with a GR>or=700 g/d and
      inseminated at <210 d. G2 (n=165)-gilts with a GR>or=700 g/d and inseminated at
      >or=210 d. G3 (n=239)-gilts with a GR<700 g/d and inseminated at >or=210 d. All
      females were fed ad libitum from 150 d on and were inseminated at their second
      estrus or later. The minimum weight at mating was 127 kg. Three parities were
      studied, with farrowing rate, litter size and culling rate being compared. At the
      first parity, G2 gilts produced, on average, one more piglet than the other
      groups (P<0.05). However, when analyzing three parities, there were no
      differences in total born (11.6 x 12.3 x 11.7), farrowing rate (87.1% x 88.7% x
      89.8%) and culling rate (30.2% x 25.3% x 28.2%) among G1-G3 groups, respectively
      (P>0.05). In conclusion, gilts, which had a minimum weight of 127 kg can be
      inseminated at their second or greater estrus, between 185 and <210 d of age,
      without impairing their productive performance over three parities.

PMID- 16431044
TI  - Determination of the extent of protein binding of antibiotics by means of an
      automated continuous ultrafiltration method.
AB  - The extent of the protein binding of a drug is an important pharmacokinetic
      parameter. In this study, the determination of the protein binding of the
      antibiotics gatifloxacin, moxifloxacin, linezolid and telithromycin to bovine
      serum albumin (BSA) and human serum albumin (HSA) was performed by means of an
      automated continuous ultrafiltration method. The continuous ultrafiltration has
      several advantages compared to classical methods like equilibrium dialysis or
      discontinuous ultrafiltration. The method is appropriate for a fast determination
      of the extent of the protein binding of a drug. In one single experiment the
      calculation of the protein binding over a wide range of different drug/protein
      ratios is possible. Comparing the results obtained with the continuous
      ultrafiltration with binding data reported in literature shows good correlation
      and proves the reliability of the method.

PMID- 16431045
TI  - Esophageal transit of the weekly film-coated risedronate (Actonel) placebo tablet
      in subjects with Kyphosis.
AB  - Risedronate sodium is a pyridinyl bisphosphonate of proven effectiveness for the
      treatment and prevention of osteoporosis and Paget's disease of the bone. The aim
      of this study was to compare the esophageal transit and gastric emptying of the
      placebo film-coated risedronate tablet when taken with 50 or 120 mL of water in
      subjects with Kyphosis. A total of 23 patients with radiologically documented
      osteoporosis participated in a single-center, open-label, crossover gamma
      scintigraphy study. The mean esophageal transit times were 15.6 s (50 mL) and
      12.0 s (120 mL) and the mean gastric emptying half-times were 20.5 min (50 mL)
      and 14.3 min (120 mL). There was no relationship between the degree of Kyphosis
      measured from lateral standing radiographs and the esophageal transit time. This
      study demonstrated that even when taken with a minimal volume of water the
      esophageal transit and gastric emptying of the film-coated 35 mg weekly
      risedronate placebo tablet was similar in kyphotic subjects to previously
      obtained results from healthy control subjects.

PMID- 16431046
TI  - Effect of drug particle size in ultrasound compacted tablets. Continuum
      percolation model approach.
AB  - The main objective of this work is to study the influence of the drug particle
      size on the pharmaceutical availability of ultrasound compacted tablets. Inert
      matrix systems containing different drug particle sizes were prepared using both,
      an ultrasound-assisted press and a traditional eccentric machine. Potassium
      chloride was used as drug model and Eudragit RS-PM as matrix forming excipient.
      The excipient particle size was kept constant. The cross-sectional
      microphotographs of ultrasound tablets show the existence of a quasi-continuum
      medium. Keeping constant the drug load, US-tablets showed very similar release
      rates, whereas for traditional tablets, an increase in the particle size resulted
      in a clear decrease in the release rate. In these tablets, the excipient forms an
      almost continuum medium. In an infinite theoretical system of these
      characteristics, the size of the drug particles will not modify the percolation
      threshold. The percolation of the excipient in this system can be assimilated to
      a continuum percolation model. In accordance with the proposed model, a lower
      influence of the drug particle size on the drug release rate was obtained for the
      US-tablets in comparison with traditional tablets. This fact can be indicative of
      the similarity of the drug percolation thresholds in these systems.

PMID- 16431047
TI  - Transdermal drug delivery using microemulsion and aqueous systems: influence of
      skin storage conditions on the in vitro permeability of diclofenac from aqueous
      vehicle systems.
AB  - The objective of this study was to evaluate the transdermal delivery potential of
      diclofenac-containing microemulsion system in vivo and in vitro. It was found
      that the transdermal administration of the microemulsion to rats resulted in 8
      fold higher drug plasma levels than those obtained after application of Voltaren
      Emulgel. After s.c. administration (3.5 mg/kg), the plasma levels of diclofenac
      reached a peak of 0.94 microg/ml at t=1 h and decreased rapidly to 0.19 microg/ml
      at t=6 h, while transdermal administration of the drug in microemulsion
      maintained constant levels of 0.7-0.9 microg/ml for at least 8 h. The transdermal
      fluxes of diclofenac were measured in vitro using skin excised from different
      animal species. In three rodent species, penetration fluxes of 53.35+/-8.19
      (furry mouse), 31.70+/-3.83 (hairless mouse), 31.66+/-4.45 (rat), and 22.89+/
      6.23 microg/cm(2)/h (hairless guinea pig) were obtained following the application
      of the microemulsion. These fluxes were significantly higher than those obtained
      by application of the drug in aqueous solution. In contrast to these results, a
      'flip-flop' phenomenon was observed when frozen porcine skin (but not fresh skin)
      was significantly more permeable to diclofenac-in-water than to the drug-in
      microemulsion. In fact, the drug penetration from the microemulsion was not
      affected by the skin storage conditions, but it was increased when an aqueous
      solution was applied. However, this unusual phenomenon observed in non-freshly
      used porcine skin places a question mark on its relevancy for in vitro
      penetration studies involving aqueous vehicle systems.

PMID- 16431048
TI  - Taste masking analysis in pharmaceutical formulation development using an
      electronic tongue.
AB  - The purpose of this study is to assess the feasibility for taste masking and
      comparison of taste intensity during formulation development using a multichannel
      taste sensor system (e-Tongue). Seven taste sensors used in the e-Tongue were
      cross-selective for five basic tastes while having different sensitivity or
      responsibility for different tastes. Each of the individual sensors concurrently
      contributes to the detection of most substances in a complicated sample through
      the different electronic output. Taste-masking efficiency was evaluated using
      quinine as a bitter model compound and a sweetener, acesulfame K, as a bitterness
      inhibitor. In a 0.2 mM quinine solution, the group distance obtained from e
      Tongue analysis was reduced with increasing concentration of acesulfame K. This
      result suggests that the sensors could detect the inhibition of bitterness by a
      sweetener and could be used for optimization of the sweetener level in a liquid
      formulation. In addition, the bitterness inhibition of quinine by using other
      known taste-masking excipients including sodium acetate, NaCl, Prosweet flavor,
      and Debittering powder or soft drinks could be detected by the e-Tongue. These
      results further suggest that the e-Tongue should be useful in a taste-masking
      evaluation study on selecting appropriate taste-masking excipients for a solution
      formulation or a reconstitution vehicle for a drug-in-bottle formulation. In
      another study, the intensity of the taste for several drug substances known to be
      bitter was compared using the e-Tongue. It was found that the group distance was
      695 for prednisolone and 686 for quinine, which is much higher than that of
      caffeine (102). These results indicate that the taste of prednisolone and quinine
      is stronger or more bitter than that of caffeine as expected. Based on the group
      distance, the relative intensity of bitterness for these compounds could be
      ranked in the following order: ranitidine HCl>prednisolone Na>quinine HCl
      approximately phenylthiourea>paracetamol>>sucrose octaacetate>caffeine. In
      conclusion, the multichannel taste sensor or e-Tongue may be a useful tool to
      evaluate taste-masking efficiency for solution formulations and to compare
      bitterness intensity of formulations and drug substances during pharmaceutical
      product development.

PMID- 16431049
TI  - Compression and compaction properties of plasticised high molecular weight
      hydroxypropylmethylcellulose (HPMC) as a hydrophilic matrix carrier.
AB  - The compression and compaction properties of plasticised high molecular weight
      USP2208 HPMC were investigated with the aim of improving tablet formation in HPMC
      matrices. Experiments were conducted on binary polymer-plasticiser mixtures
      containing 17 wt.% plasticiser, and on a model hydrophilic matrix formulation. A
      selection of common plasticisers, propylene glycol (PG) glycerol (GLY), dibutyl
      sebacate (DBS) and triacetin (TRI), were chosen to provide a range of
      plasticisation efficiencies. T(g) values of binary mixtures determined by Dynamic
      Mechanical Thermal Analysis (DMTA) were in rank order
      PG>GLY>DBS>TRI>unplasticised HPMC. Mean yield pressure, strain rate sensitivity
      (SRS) and plastic compaction energy were measured during the compression process,
      and matrix properties were monitored by tensile strength and axial expansion post
      compression. Compression of HPMC:PG binary mixtures resulted in a marked
      reduction in mean yield pressure and a significant increase in SRS, suggesting a
      classical plasticisation of HPMC analogous to that produced by water. The effect
      of PG was also reflected in matrix properties. At compression pressures below 70
      MPa, compacts had greater tensile strength than those from native polymer, and
      over the range 35 and 70 MPa, lower plastic compaction values showed that less
      energy was required to produce the compacts. Axial expansion was also reduced.
      Above 70 MPa tensile strength was limited to 3 MPa. These results suggest a
      useful improvement of HPMC compaction and matrix properties by PG plasticisation,
      with lowering of T(g) resulting in improved deformation and internal bonding.
      These effects were also detectable in the model formulation containing a minimal
      polymer content for an HPMC matrix. Other plasticisers were largely ineffective,
      matrix strength was poor and axial expansion high. The hydrophobic plasticisers
      (DBS, TRI) reduced yield pressure substantially, but were poor plasticisers and
      showed compaction mechanisms that could be attributed to phase separation. The
      effect of different plasticisers suggests that the deformation characteristics of
      this HPMC in the solid state is dominated by hydroxyl mediated bonding, rather
      than by hydrophobic interactions between methoxyl-rich regions.

PMID- 16431050
TI  - Anti-platelet effects of bioactive compounds isolated from the bark of Rhus
      verniciflua Stokes.
AB  - It has previously been shown that EtOAc extracts of Rhus verniciflua Stokes (RVS)
      inhibit the platelet aggregation response. In this report, bioassay-guided
      fractionation using ADP-, arachidonic acid-, and collagen-induced human platelet
      aggregation by a whole blood aggregometer yielded the bioactive compounds
      isomaltol and pentagalloyl glucose from different highly effective fractions. In
      addition, column chromatography of fractions from RVS yielded another five
      compounds: butin, fisetin, sulfuretin, butein and 3,4',7,8-tetrahydroxyflavone.
      We investigated the effects of bioactive compounds from RVS fractions on several
      markers of platelet activation using receptor expression on platelet membranes,
      including glycoprotein IIb/IIIa (CD41), GPIIb/IIIa-like expression (PAC-1) and P
      selectin (CD62), and intracelluar calcium mobilization responses by flow
      cytometry in healthy subjects. Dose-dependent inhibition of platelet aggregation
      and significantly decreased platelet activation were observed for the isomaltol-
      and pentagalloyl glucose-treated platelets, respectively. These results show that
      isomaltol and pentagalloyl glucose from the bark of Rhus verniciflua Stokes have
      potent anti-platelet activity and emphasize the need to further examine the
      mechanism of these active compounds for platelet modulation.

PMID- 16431051
TI  - Danshen prevents the occurrence of oxidative stress in the eye and aorta of
      diabetic rats without affecting the hyperglycemic state.
AB  - Oxidative stress has been implicated in the pathogenesis of diabetic
      complications. We have previously demonstrated the occurrence of oxidative stress
      in the eye and aorta but not in the kidney of diabetic rats. In the present study
      we have investigated the effects of danshen, a herb used in traditional Chinese
      medicine to treat ailments related to diabetic complications, on the onset of
      oxidative stress in the above tissues. Diabetic rats were treated with 3 g/kg of
      danshen via oral intubation for 7 weeks. Afterwards, the tissue levels of
      glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA),
      a marker of oxidative stress, were measured. Our results showed that danshen
      treatment did not alter the hyperglycemic status of the diabetic animals.
      However, the GSH levels were normalized in both the eye and aorta of the diabetic
      rats when these rats were administered with danshen. Administration with danshen
      also restored the level of MDA in the eye and aorta of the diabetic rats to that
      found in the control rats. These changes, however, were not observed in the
      kidney where oxidative stress did not occur. These results suggested that oral
      administration of danshen can effectively prevent the occurrence of oxidative
      stress in the eye and aorta of the diabetic rats. Furthermore, danshen treatment
      did not affect the blood glucose concentration of the animals irrespective of
      their diabetic state. These data therefore provide important information on mode
      of action of danshen, thereby establishing a basis for this herb to be used as a
      supportive treatment regime to ameliorate the severity of diabetic complications.

PMID- 16431052
TI  - A quantitative differentiation method for plastic bags by infrared spectroscopy,
      thickness measurement and differential scanning calorimetry for tracing the
      source of illegal drugs.
AB  - Fifty shopping bags, commonly encountered in the packaging of drug doses, were
      characterized by thickness measurements, infrared spectroscopy and differential
      scanning calorimetry. By these very straightforward and inexpensive techniques,
      without sample preparation, nearly all the considered samples could be
      discriminated. Ninety-seven percent of the possible pairs of white, apparently
      similar dull polymer films were differentiated. The rather large degree of
      variability existing in grocery bags, even though they are mass produced, was
      shown, confirming that these items can be useful in tracing the source of illicit
      drug doses.

PMID- 16431054
TI  - Potentiality of 3D laser profilometry to determine the sequence of homogenous
      crossing lines on questioned documents.
AB  - The determination of the sequence of line crossings is still a current problem in
      the field of forensic documents examination. Optical examination, lifting
      technique, ESDA technique, and electron microscopy are the most widely used
      methods for the determination of the writing order of crossing texts. However, at
      present many examinations of intersecting lines result in an inconclusive
      opinion, particularly if the same type and colour of ink is involved. This paper
      presents the potentiality of the 3D laser profilometry, which has been to
      determine the chronological sequence of homogenous "crossing lines". The laser
      profilometry, illustrated in this paper, has been developed on a conoscopic
      holography based system. It is a non-contact three-dimensional measuring system
      that allows producing holograms, even with incoherent light, with fringe periods
      that can be measured precisely to determine the exact distance to the point
      measured. This technique is suitable to obtain a 3D micro-topography with high
      resolution also on surfaces with unevenness reflectivity (usual for the paper
      surface). The proposed technique is able to obtained 3D profile in non-invading
      way. Therefore, the original draft are not physically or chemically modified,
      allowing a multi-analysis in different times. The experiments performed with line
      crossings database show that the proposed method is able of "positive
      identification" of writing sequence in the majority of the tests. In absence of a
      positive identification, the result has been "inconclusive" (no false
      determination did occur in this work).

PMID- 16431055
TI  - The future of forensic and crime scene science. Part II. A UK perspective on
      forensic science education.
AB  - This paper builds on the views presented by the author at 'The Future of Forensic
      and Crime Scene Science Conference'. Forensic science has become an increasingly
      prominent area of science within the last 10 years. This increasing prominence
      together with popularity in the subject has seen the number of undergraduate
      students studying forensic science related courses at UK Universities increase
      rapidly in just 5 years and there are no short term signs of this trend reducing.
      In 2005, there were 450 courses with forensic in the title offered by higher
      education institutes. Although the forensic community has expressed its concern
      that job prospects for these students wishing to pursue careers as forensic
      scientists will be limited numbers of students undertaking science courses have
      still increased. The increase in students studying forensic science comes in an
      era of decreasing science numbers in higher education with the potential to
      produce high calibre science graduates with sought after skills in critical
      thinking, analysis, interpretation and communication. Technology has continued to
      advance at a similar pace providing those responsible for managing crime with a
      need and opportunity to identify and predict new and future applications of
      science and technology; not just in reducing and detecting crime but also in
      predicting how technology will be used by criminals in the future. There is
      therefore a need for forensic science users, providers and educators to identify
      the knowledge and skills required by forensic scientists and crime investigators
      of the future to ensure that technology continues to be used and applied to its
      full advantage. This provides universities an opportunity to contribute to the
      development of both the practice and practitioners of forensic science. This
      paper outlines the current issues facing universities in relation to forensic
      science and identifies their future role in providing high quality relevant
      courses for future forensic practitioners; developing current forensic
      practitioners through their participation in applied research, short courses,
      conferences and qualifications linked to professional practice; and supporting
      and developing the practice of forensic and crime scene science, through the
      identification, engagement and dissemination of pure and applied research.

PMID- 16431056
TI  - The future of forensic and crime scene science. Part I. A UK forensic science
      user and provider perspective.
AB  - This paper presents an overview of the views expressed by UK forensic science
      users and providers during the Centre for Forensic Investigation's 1 day
      conference 'The Future of Forensic and Crime Scene Science' and is set in the
      context of the changing national agenda and likely advances in current and future
      technology. It begins by examining the success of the Home Office DNA Expansion
      Programme and future demands of the Criminal Justice System, highlighting the
      changing use of forensic science both at the crime scene and within the forensic
      process itself. In particular, the use of forensic science at the early stages of
      an investigation to provide intelligence and support the decision making process
      is discussed together with the need to adopt a partnership approach to tackling
      crime and its causes. Key system and technological drivers for performance
      improvement and change are identified and the likely timescales and implications
      of their introduction are discussed. Finally, the Home Office plans to build on
      the success of the DNA Expansion Programme, through the introduction of the
      proposed Home Office Forensic Integration Strategy, are explored and the paper
      concludes by highlighting the benefits, implications and issues arising from the
      changing and developing use of forensic science.

PMID- 16431057
TI  - Allele frequencies of six miniSTR loci of three ethnic populations in Singapore.
AB  - MiniSTR loci has demonstrated to be an effective approach to recover genetic
      information from degraded sample, due to the improved PCR efficiency of their
      reduced PCR product sizes. This study investigated the allele frequency of six
      miniSTR loci, D1S1677, D2S441, D4S2364, D10S1248, D14S1434 and D22S1045, in three
      Singapore populations. All loci showed a moderate degree of polymorphism with
      observed heterozygosity >0.6 for all three populations. The allele frequencies,
      forensic parameters and heterozygosity comparison with other CODIS STR in similar
      populations are presented.

PMID- 16431058
TI  - Lethal self administration of propofol (Diprivan). A case report and review of
      the literature.
AB  - The death of a female anaesthesiologist is reported. Although the situation at
      the scene indicated propofol overdose-related death, self-administration of such
      high doses of propofol was unlikely, given the pharmacological properties of this
      drug. The analysis of the situation at the scene and the toxicological analysis
      in which the blood and liver propofol concentrations were 2.40microg/ml and
      0.56microg/g, respectively, supported the conclusion that the death was a
      consequence of propofol self-administration at therapeutic doses from a person
      who used the drug on chronic basis seeking to its euphoric effects. However,
      because the toxic concentrations of propofol in non-intubated patients may be
      different from those intubated and fully supported in the operating room or in
      the intensive care unit, a mere interpretation of the blood and tissue
      concentrations of propofol in the toxicological analysis can confirm the drug
      intake but it may be of limited diagnostic significance without taking into
      account this difference.

PMID- 16431059
TI  - Association between human beta defensin expression and cholesteatoma formation.
AB  - OBJECTIVE: To investigate an association between human beta defensin (hBD)
      expression and cholesteatoma formation. METHODS: hBD-2 mRNA expressions were
      assessed in healthy external acoustic meatus skin organ cultures before and after
      stimulation with Pseudomonas aeruginosa. In addition, hBD-1 and hBD-2 protein
      production of stimulated and non-stimulated external acoustic meatus skin was
      visualized by immunohistochemistry. Furthermore, hBD-1 and hBD-2 mRNA expression
      was analyzed in 25 external acoustic meatus skin, 29 cholesteatoma, and 18 non
      cholesteatoma control samples. Non-stimulated meatal tissue preparation did not
      express hBD-2, whereas incubation with P. aeruginosa demonstrated hBD-2
      induction. RESULTS: The hBD-1 mRNA expression was detected in cholesteatoma
      (14/17), meatal skin, and middle ear mucosa (11/18). hBD-2 mRNA expression was
      shown in eight cholesteatoma (28.5%) and in three middle ear mucosa tissue
      samples (37.5%). CONCLUSION: Our data suggest constitutional hBD-1 and inducible
      hBD-2 expression in chronic middle ear infection and cholesteatoma. Failure of
      hBD-1 and hBD-2 expression might dispose to exacerbation of cholesteatoma
      disease. The organ culture model of the external acoustic meatus skin is
      effective in order to evaluate germ stimulation experiments.

PMID- 16431060
TI  - Analysis of 95 cases of squamous cell carcinoma of the external and middle ear.
AB  - OBJECTIVE: To analyze the clinical characteristics, 5-year survival, and
      prognostic factors of squamous cell carcinoma (SCC) of the external and middle
      ear. METHODS: A multi institutional study. Ninety five cases of patients from 10
      institutions were reviewed on their age and sex distribution, initial complaints,
      stages, tumor locations, treatments, and outcomes. Prognostic factors were
      discussed based on the Pittsburgh staging system. RESULTS: This disease seems to
      appear in the elderly with a peak age of 50-69 years. Males appear to be more
      predisposed than females with an odd ratio of 1.7. The initial complaints were
      not typical, while 12.6% of patients presented a history of recurrent otitis
      externa or chronic otitis media. Regional metastasis was recognized in 13.7% of
      patients, while no distant metastasis was confirmed. SCC located in the external
      ear could be detected in an earlier stage than that in the middle ear. The
      overall 5-year survival was 66.8% in total, and decreased significantly with
      stage. SCC in stages I and II was susceptible to each therapeutic strategy with a
      5-year survival of 100%. Operation combined with radiotherapy and/or chemotherapy
      was the major treatment for stages III and IV SCC, while radiotherapy and
      chemotherapy were applied mainly for those who had been considered inappropriate
      for operation. The overall survival was 67.2% for stage III and 29.5% for stage
      IV, and operation with pathologically tumor free margin could improve the
      survival to 72.7% when combined with radio- and chemotherapy. Stage, completeness
      of operation with tumor free margin, recurrence, and metastasis have significant
      influence on survival. CONCLUSION: Local infiltration seems to be the main
      behavior of SCC in the external and middle ear. Early diagnosis and treatment
      were important because SCC in the earlier stage is susceptible to be cured. For
      tumors of advanced stage, operation should be performed with pathologically tumor
      free margin, and operation combined with radiotherapy and chemotherapy could
      improve the survival. Tumor stage adds more influence on survival than its
      location. Recurrence and metastasis mainly occur in advanced stages and result in
      a poor survival.

PMID- 16431061
TI  - The impact of incubating the throat culture for 72 h on the diagnosis of group A
      beta-hemolytic streptococci.
AB  - OBJECTIVE: The accurate detection and treatment of group A beta-hemolytic
      streptococcal pharyngitis is important to prevent the potential sequels. Throat
      culture remains the gold standard for the diagnosis of streptococcal pharyngitis.
      Many authors recommended 48 h incubation time for the isolation of group A
      Streptococcus (GAS). In this study the diagnostic efficacy of prolonging the
      incubation time of throat cultures to 72 h for isolation of GAS was researched.
      METHODS: Throat swab specimens were inoculated to 5% sheep blood agar plate and
      incubated at 37 degrees C, and evaluated at the 24th hour. GAS negative plates
      were incubated again for another 24h and read at the 48th hour. Negative plates
      at 48 h were incubated again, read at the 72nd hour, and positive results of all
      measurements were evaluated. RESULTS: A total of 367 cultures were examined. At
      the 24th hour evaluation 34 (9.3%) cultures were positive for GAS. Evaluation of
      333 cultures that were found to be negative in the first 24th hour evaluation
      revealed 44 (13.6%) positive cultures at 48th hour evaluation. Out of 289
      cultures that were negative during the 48th hour evaluation, an additional 13
      (4.7%) cultures were found to be positive during the 72nd hour evaluation. The
      agreement between 24th-48th and 24th and 72nd were both moderate (kappa 0.54 and
      0. 46, respectively), and between 48th and 72nd hour was very good (kappa: 0.90).
      CONCLUSION: Throat cultures that are negative for GAS at 24h should be incubated
      for second day. We conclude that, to confirm the throat cultures GAS negative,
      results of throat cultures need to be incubated for 72 h, since 72nd hour
      evaluations revealed additional 5% positive results.

PMID- 16431062
TI  - Comparative study of fixed time versus intensity trade and fixed intensity versus
      time trade tests in sound lateralization.
AB  - OBJECTIVE: In the perception of sound lateralization a sound source exists in the
      side that the sound reaches an ear earlier in time or louder in intensity than
      the other ear. It is an imaginary phenomenon where the direction of sound is
      lateralized by an interaural time difference (ITD) and an interaural intensity
      difference (IID) of sound by both ears. It is speculated from pathophysiological
      findings that ITD and IID are processed by different pathways, but it has been
      not yet proved which of them is predominant in sound lateralization. The time
      difference can be traded by the intensity difference (fixed time versus intensity
      trade), and vice versa (fixed intensity versus time trade). In order to
      investigate predominance in this trade, we measured possible differences in
      effects by ITD and IID using two opposite trade phenomena of time versus
      intensity trade and intensity versus time trade. METHODS: The fixed time versus
      intensity trade test for selected narrow-band noise was investigated in 30
      subjects with normal hearing. Using headphones, the subjects were instructed to
      push the button when the sound bias generated by fixed ITD (4 dB, 6 dB, 8 dB, 10
      dB, 12 dB, 14 dB, 16 dB, 18 dB, 20 dB) was traded by gradually increased IID. The
      plot figure with fixed ITD and required IID to trade was made. It was compared
      with similar fixed intensity versus time trade test in 12 subjects with normal
      hearing. The fixed ITD (200-600 micros) was traded by gradually increased IID and
      the plot figure was made. RESULTS: In fixed time versus intensity trade test,
      each fixed ITD could be traded with an average of 6 dB of IID. On the other hand,
      in fixed intensity versus time trade test, ITD required to trade fixed IID
      increased, in proportion to fixed IID increased. CONCLUSION: It is concluded that
      predominance exists. In fixed time versus intensity trade test, the uniform
      amount of IID is required to trade the different ITD. However, in the novel fixed
      intensity versus time trade test, the phenomenon was in completely different
      manner that ITD in proportion to the given IID is required to trade.

PMID- 16431063
TI  - Intramasseteric schwannoma in a child.
AB  - Schwannoma arising in muscle is rare. We treated a very unusual case of
      schwannoma originating in the masseter muscle in a 12-year-old boy, who presented
      with a 1-year history of a painless left cheek mass. CT and MRI revealed that the
      mass existed in the masseter muscle. It was extirpated under general anesthesia
      without postoperative sequelae. The whitish mass was solid and encapsulated, and
      pathologic examination confirmed the diagnosis of schwannoma consisting of Antoni
      A and Antoni B areas. Definitive diagnosis of schwannoma before surgery is
      usually difficult; hence, histological examination during or after surgery is, in
      most cases, decisive. However, schwannoma should be considered in the
      preoperative differential diagnosis of intramuscular tumor, despite its rare
      occurrence, since postoperative neurological sequelae may occur.

PMID- 16431065
TI  - Imaging and differential diagnosis of primary bone tumors and tumor-like lesions
      of the spine.
AB  - Primary bone tumors and tumor-like lesions of the spine and sacrum are rare. A
      wide variety of benign and malignant lesions can arise in the spine and sacrum.
      Specific diagnosis is based on the location, matrix appearance and patient's age
      at time of presentation. In this location CT is often necessary for matrix
      characterization, particularly, detection of mineralization. MRI can be helpful
      for further characterization and radiological differential diagnosis. An overview
      of age distribution and imaging features including pattern for differential
      diagnosis is presented for the most frequent primary spinal bone tumors and tumor
      like lesions.

PMID- 16431064
TI  - Atypical manifestations of multiple myeloma: radiological appearance.
AB  - Diagnostic procedures performed on patients with multiple myeloma typically
      reveal lytic bone lesions, osteopenia or osteoporosis, bone marrow infiltration
      by plasma cells as well as overproduction of immunoglobulin or light chains in
      the serum or urine. Skeletal manifestations are extremely variable and the
      unusual forms have been described extensively. Extramedullary plasma-cell tumours
      (plasmocytoma) are found in about 5% of newly diagnosed patients with multiple
      myelomas. In this paper we present eight patients with atypical forms of multiple
      myeloma.

PMID- 16431066
TI  - Imaging of congenital anomalies and variations of the caudal spine and back in
      neonates and small infants.
AB  - Spinal dysraphisms are categorized in open dysraphisms with prominent abnormal
      nervous tissue above the skinlevel and closed dysraphisms with a skin covered
      malformation. Especially the occult dysraphisms are marked by suspect skin masses
      and other dermal anomalies. The purpose of this review is to demonstrate the
      indications and spectrum of spinal sonography in neonates and infants. In
      comparison typical dysraphisms are demonstrated in sonography and MR Imaging. We
      demonstrate the value of ultrasound in comparison to MRI and describe a usefull
      handling of the methods in neonates and infants. The differentiation between the
      potentially dangerous dimples associated with dermal sinus, which can lead to
      meningitis and the harmless coccygeal dimple in the cranial gluteal cleft is
      presented. An inconspicious examination does not need a further imaging, but
      suspicious results of sonography need an MR imaging dependent of clinical
      conditions. Neurologically conspicious infants need MR imaging completed by
      sonography. Great advantages of sonography are the real time examination and the
      potential to show oscillations of the conus, filum and cauda equina in M-mode
      imaging.

PMID- 16431067
TI  - Threshold-dependent variability of coronary artery calcification measurements --
      implications for contrast-enhanced multi-detector row-computed tomography.
AB  - INTRODUCTION: The present study investigated the threshold-dependent variability
      of coronary artery calcification (CAC) measurements and the potential to quantify
      CAC in contrast-enhanced multi-detector row-computed tomography (MDCT). METHODS:
      We compared the mean CT attenuation of CAC to luminal contrast enhancement of the
      coronary arteries in 30 patients (n = 30) undergoing standard coronary contrast
      enhanced spiral MDCT. The modified Agatston score [AS], calcified plaque volume
      [CV], and mineral mass [MM]) at four different thresholds (130, 200, 300, and 400
      HU) were measured in 50 patients who underwent non-contrast-enhanced MDCT.
      RESULTS: Mean CT attenuation of CAC was similar to the attenuation of the
      contrast-enhanced coronary lumen (CAC 297.1 +/- 68.7 HU versus 295 +/- 65 HU (p <
      0.0001), respectively). Above a threshold of 300 HU CAC measurements
      significantly varied to standard measurements obtained at a threshold of 130 HU
      (p < 0.0001). The threshold-dependent variation of MM measurements was
      significantly smaller than for AS and CV (130 HU versus 400 HU: 63, 75, and 81,
      respectively; p < 0.001). These differences resulted in a change of age and
      gender based percentile category for AS in 78% of subjects. DISCUSSION: We
      demonstrated that CAC measurements are threshold dependent with MM measurements
      having significantly less variation than AS or CV. Due to the similarity of mean
      CT attenuation of CAC and the contrast-enhanced coronary lumen accurate
      quantification of CAC may be difficult in standard coronary contrast-enhanced
      spiral MDCT.

PMID- 16431068
TI  - Microbial community structure of sandy intertidal sediments in the North Sea,
      Sylt-Romo Basin, Wadden Sea.
AB  - Molecular biological methods were used to investigate the microbial diversity and
      community structure in intertidal sandy sediments near the island of Sylt (Wadden
      Sea) at a site which was characterized for transport and mineralization rates in
      a parallel study (D. de Beer, F. Wenzhofer, T. Ferdelman, S.E. Boehme, M.
      Huettel, J.E.E. van Beusekom, M.E. Bottcher, N. Musat, N. Dubilier, Transport and
      mineralization rates in North Sea sandy intertidal sediments, Sylt-Romo Basin,
      Wadden Sea, Limnol. Oceanogr. 50 (2005) 113-127). Comparative 16S rRNA sequence
      analysis revealed a high bacterial diversity. Most sequences retrieved by PCR
      with a general bacterial primer set were affiliated with Bacteroidetes,
      Gammaproteobacteria, Deltaproteobacteria and the Pirellula cluster of
      Planctomycetales. Fluorescence in situ hybridization (FISH) and slot-blot
      hybridization with group-specific rRNA-targeted oligonucleotide probes were used
      to characterize the microbial community structure over depth (0-12 cm) and
      seasons (March, July, October). We found high abundances of bacteria with total
      cell numbers up to 3 x 10(9) cells ml(-1) and a clear seasonal variation, with
      higher values in July and October versus March. The microbial community was
      dominated by members of the Planctomycetes, the Cytophaga/Flavobacterium group,
      Gammaproteobacteria, and bacteria of the Desulfosarcina/Desulfococcus group. The
      high abundance (1.5 x 10(7)-1.8 x 10(8) cells ml(-1) accounting for 3-19% of all
      cells) of presumably aerobic heterotrophic polymer-degrading planctomycetes is in
      line with the high permeability, deep oxygen penetration, and the high rates of
      aerobic mineralization of algal biomass measured in the sandy sediments by de
      Beer et al. (2005). The high and stable abundance of members of the
      Desulfosarcina/Desulfococcus group, both over depth and season, suggests that
      these bacteria may play a more important role than previously assumed based on
      low sulfate reduction rates in parallel cores (de Beer et al., 2005).

PMID- 16431069
TI  - A health assessment tool for multiple risk factors for obesity: results from a
      pilot study with UK adults.
AB  - OBJECTIVE: Although many individual health behaviours have been implicated in the
      current rise in obesity levels, their confounding or cumulative effects have yet
      to be established. This study piloted a measure of multiple risk factors for
      obesity, designed to assess their relative importance at individual and
      population levels. METHODS: A 100-item, user-friendly, self-report questionnaire,
      was completed by 80 adult volunteers (67% female, age range 19-73 years), and
      related to Body Mass Index (BMI). RESULTS: Dietary factors significantly related
      to BMI were higher amount of food consumption and more non-hunger related eating.
      BMI was strongly related to both negative attitudes/emotions towards and negative
      social influences on physical activity/exercise. Higher BMI was also related to
      less participation in physical activity/exercise, more sedentary leisure pursuits
      (e.g. TV watching) and lower general activity levels (e.g. more car usage). A
      regression analysis of all risk factors explained around 56% of the variance in
      BMI. CONCLUSION: The pilot measure was able to differentiate between weight
      groups on a number of risk factors. The strong associations found between BMI and
      attitudes, emotions and social influences on eating and activity behaviours may
      help explain why many diet and exercise regimes are unsuccessful. PRACTICE
      IMPLICATIONS: Results demonstrate that an easy-to-complete, self-report tool of
      multiple risk factors for obesity has potential as a health assessment tool for
      use by health professionals.

PMID- 16431070
TI  - Physicians' opening questions and patients' satisfaction.
AB  - OBJECTIVE: To determine the association between the format of physicians' opening
      questions that solicit patients' presenting concerns and patients' post-visit
      evaluations of (i.e., satisfaction with) the affective-relational dimension of
      physicians' communication. METHODS: Videotape and questionnaire data were
      collected from visits between 28 primary-care physicians and 142 adult patients
      with acute problems. Factor analysis resulted in three dependent variables
      derived from the 9-item Socioemotional Behavior subscale of the Medical Interview
      Satisfaction Scale. RESULTS: Question format was significantly, positively
      associated with patients' evaluations of physicians' listening (p=.028) and
      positive affective-relational communication (p=.046). CONCLUSION: Patients desire
      opportunities to present concerns in their own time and terms regardless of how
      extensively they act on this opportunity. PRACTICE IMPLICATIONS: Visits should be
      opened with general inquiries (e.g., What can I do for you today?) versus closed
      ended requests for confirmation (e.g., Sore throat, huh?).

PMID- 16431071
TI  - Do themes in consumer medicines information literature reviews reflect those
      important to stakeholders?
AB  - OBJECTIVE: To compare the themes emerging from a stakeholder workshop on
      consumers' medicines information with themes in relevant published reviews.
      METHODS: A stakeholder workshop was held to permit consumer orientation of a
      systematic review of consumer medicines information. Analysis of the workshop
      outputs was compared to a content analysis of the identified published reviews.
      RESULTS: The workshop generated a range of responses inductively grouped into 12
      over-arching themes. No reviews tackled all of these themes, nor addressed
      'informed choice and autonomy'. More recent reviews reflected more workshop
      themes than older ones, suggesting a temporal trend towards a greater sensitivity
      to consumer issues. The most common workshop themes were covered by all reviews.
      Six themes in the reviews were related to traditional professional concerns
      including compliance, which did not arise in the workshop. CONCLUSION: The
      results highlight a mismatch between the themes in previous published reviews and
      the themes emerging from the workshop. The most commonly reflected themes in
      reviews conform to the 'patient education' model of discourse, while workshop
      themes less often echoed in reviews reflect the discourse of 'patient
      empowerment'. PRACTICE IMPLICATIONS: The findings suggest the importance of
      involving patients in the development of patient literature from the outset.

PMID- 16431072
TI  - The implementation of a harm minimisation model for the identification and
      treatment of over-the-counter drug misuse and abuse in community pharmacies in
      Northern Ireland.
AB  - OBJECTIVE: This study tested an intervention model which sought to minimise over
      the-counter (OTC) drug misuse and abuse in community pharmacies. METHOD:
      Pharmacists in six community pharmacies in the Greater Belfast area volunteered
      to participate in the study. The intervention model consisted of client
      identification and recruitment, treatment and referrals, and finally follow-up
      data collection and outcome measurements. All pharmacists participated in semi
      structured interviews to explore their views and experiences of the study.
      RESULTS: Pharmacists identified 196 cases of suspected abuse/misuse. Pharmacists
      approached 70 of the identified clients during the six-month study; some clients
      agreed to stop using the product of abuse/misuse, used an alternative, or had
      been switched to a maintenance prescription under general practitioner (GP)
      supervision. No client proceeded to completion of the follow-up phase (e.g.
      health-related quality of life). Analysis of the interviews revealed that
      pharmacists had encountered some difficulties in approaching potential clients,
      but had used skills gained in the study in other aspects of their practice.
      CONCLUSIONS: Some difficulties were encountered in implementing the harm
      minimisation model, but these may be alleviated by further training and greater
      collaborative working. PRACTICE IMPLICATIONS: Notwithstanding the challenges
      faced in the study, this approach to harm minimisation should be considered for
      wider implementation in community pharmacy.

PMID- 16431074
TI  - The role of apoptotic or nonapoptotic cell death in determining cellular response
      to anticancer treatment.
AB  - AIMS: Apoptosis, an early response cell death, is a useful marker for predicting
      tumour response after anticancer treatment; however, late-response cell death or
      nonapoptotic cell death, autophagy, can also be observed. This article reviews a
      rational model for predicting tumour response by assessing the influence of
      nonapoptotic cell death, and thereby developing a more efficient strategy for
      enhancing the therapeutic effect of anticancer treatment. METHOD: Literature
      search of clinical and experimental studies on "cell death and cancer" using
      established databases, including PUBMED. FINDINGS: Although induction of
      apoptosis may not contribute to overall tumour response, nonapoptotic cell death
      such as autophagy, which may be triggered by apoptosis, still occurs. Anticancer
      treatment-induced apoptosis is regulated by the balance of proapoptoic and
      antiapoptoic proteins through mitochondria, and resistance to apoptosis is
      mediated by Bcl-2-dependent and Akt-dependent pathways. Bcl-2 partially inhibits
      nonapoptotic cell death as well as apoptosis, whereas Akt inhibits both apoptotic
      and nonapoptotic cell death through several target proteins. CONCLUSIONS: Drug
      sensitivity is likely correlated with the accumulation of apoptotic and
      nonapoptotic cell deaths, which may influence overall tumour response in
      anticancer treatment. The ability to predict overall tumour response from the
      modulation of several important cell death-related proteins may result in a more
      efficient strategy for improving the therapeutic effect.

PMID- 16431073
TI  - Myostatin inhibits differentiation of bovine preadipocyte.
AB  - We investigated the effect of myostatin on the differentiation of bovine
      preadipocyte. Stromal-vascular cells containing preadipocytes were prepared from
      perirenal adipose tissue of approximately 30-month-old Japanese Black steers.
      After confluence, the differentiation was induced by 1-methyl-3-isobutyl
      xanthine, dexamethasone, insulin, and troglitasone for 2 days, and then
      subsequently cultured for 6 days. The cells were treated with myostatin during
      the induction of differentiation (the early phase of differentiation) or
      throughout the differentiation period. We measured the terminal differentiation
      markers such as glycerol-3-phosphate dehydrogenase activity, lipid accumulation,
      and the expression of adipocyte fatty acid-binding protein mRNA at the end of
      cultures. The treatment with myostatin throughout the differentiation period
      severely suppressed the induction of all differentiation markers. The treatment
      with myostatin in the early phase of differentiation also suppressed the
      induction of terminal differentiation markers but three-fold higher dose of
      myostatin was required for the suppression compared with its treatment throughout
      the differentiation period. Myostatin treatment reduced the expression of
      peroxisome proliferator-activated receptor (PPAR) gamma mRNA and interfered with
      the induction of CCAAT/enhancer binding protein (C/EBP) alpha mRNA. We also
      observed that follistatin stimulates preadipocyte differentiation in the presence
      of myostatin. These results suggest that myostatin inhibits bovine preadiopocyte
      differentiation through suppressing PPARgamma and C/EBPalpha mRNA expressions and
      that follistatin counteracts the suppressive effect of myostatin.

PMID- 16431075
TI  - Condition-specific coregulation with cis-regulatory motifs and modules in the
      mouse genome.
AB  - Deciphering genetic regulatory codes remains a challenge. Here, we present an
      effective approach to identifying in vivo condition-specific coregulation with
      cis-regulatory motifs and modules in the mouse genome. A resampling-based
      algorithm was adopted to cluster our microarray data of a stress response, which
      generated 35 tight clusters with unique expression patterns containing 811 genes
      of 5652 genes significantly altered. Database searches identified many known
      motifs within the 3-kb regulatory regions of 40 genes from 3 clusters and modules
      with six to nine motifs that were commonly shared by 60-100% of these genes. The
      upstream regulatory region contained the highest frequency of these common
      motifs. CisModule program predictions were comparable with the results from
      database searches and found four potentially novel motifs. This result indicates
      that these motifs and modules could be responsible for gene coregulation of the
      stress response in the lacrimal gland.

PMID- 16431076
TI  - Measuring mouse sperm parameters using a particle counter and sperm quality
      analyzer: a simple and inexpensive method.
AB  - This study examined a method for analyzing the count, motility, and morphology of
      mouse epididymal sperm, optimizing the diluent, incubation time, sample
      concentration, and temperature, using a particle counter (CDA-500) to count and
      size sperm and a sperm quality analyzer (SQA-IIC) to measure sperm motility,
      quantified as the sperm motility index (SMI). The optimal conditions consisted of
      a 30-min incubation in D-MEM (Dulbecco's modified Eagle's medium; considering
      cost and availability) at 37 degrees C, with 5 x 10(6)cells mL(-1) in the
      original solution. Furthermore, the influence of formalin fixation, and the
      correlation between the automated counter and a manual method were investigated.
      The sample fixation had no marked effect on the sperm count or morphology
      assessment. A linear correlation was observed between the manual and automated
      methods (y=0.920x +0.276; r(2)=0.571; p<0.001; range: (3-6) x 10(6)). The
      suitability of the proposed method was confirmed using spermatozoa prepared from
      mice treated with the reproductive toxin diethylstilbestrol (DES). Using sperm
      from the cauda epididymidis on one side per mouse, we confirmed that measurement
      of these sperm parameters using the two devices was simple, rapid, inexpensive,
      and reproducible.

PMID- 16431077
TI  - Influence of Fusarium-toxin contaminated feed on initial quality and meiotic
      competence of gilt oocytes.
AB  - Mycotoxins are contaminants of animal feed that can impair fertility and cause
      abnormal fetal development in farm animals. The aim of the present study was to
      investigate the influence of Fusarium-toxin contaminated feed on cumulus
      morphology and maturation of pig oocytes. Naturally with the Fusarium-toxins
      deoxynivalenol (DON) and zearalenone (ZON) contaminated wheat was included in
      feed for gilts at increasing proportions which resulted in increasing dietary
      concentrations of both toxins (in mgtoxin/kg feed: Group 1 (control), 0.21 and
      0.004; Group 2, 3.07 and 0.088; Group 3, 6.1 and 0.235; Group 4, 9.57 and 0.358,
      for DON and ZON, respectively). Oocytes were recovered from gilt ovaries by
      follicle aspiration after ovario-hysterectomy. Granulosa cells were analyzed for
      the expression of the P450(SCC) and 3beta-HSD mRNA by RT-PCR and additionally for
      P450(SCC) protein by Western blotting. Neither the expression of the P450(SCC)
      nor of the 3beta-HSD mRNA or the abundance of the P450(SCC) protein was
      significantly influenced by the mycotoxin application. The distribution of
      different cumulus cell morphologies was not influenced by group. At the time of
      recovery, oocytes with compact cumuli in Groups 3 and 4 showed a reduced
      proportion having immature chromatin in comparison to that for Groups 1 and 2.
      The proportion of oocytes having degenerated meiotic chromatin was significantly
      higher in Group 4 than in the other groups. The proportion of oocytes reaching
      metaphase II in culture was significantly lower in Groups 3 and 4 than in Group
      1, and tended to be lower in Group 2 than in Group 1. We conclude that oocyte
      quality is significantly reduced by feeding of Fusarium-toxins to gilts.

PMID- 16431078
TI  - Genotyping of hepatitis B virus (HBV) by oligonucleotides microarray.
AB  - Oligonuleotides (oligo) microarray is a promising method for virus genotyping. In
      this study, we developed an oligo microarray used for genotyping hepatitis B
      virus (HBV). It consists of 15 probes targeting HBV genotypes A-G and two
      genotypes of apes, and one conserved probe selected from the HBV pre-S region. To
      test a clinical sample, the gene targets of clinical samples were amplified and
      labelled with Cy5-dCTP in a PCR reaction using primers covering the flanking
      region of the HBV pre-S gene. Following purification, the labelled PCR products
      were hybridized to the microarray. In an analysis of 96 HBV patients' serum
      samples using our developed microarray, we identified 34 genotype B, 60 genotype
      C and 2 genotypes B/C coinfection samples. Sequencing results of 24 randomly
      selected samples agreed 100% with microarray data. Geographic distribution of
      genotypes C and B was also divergent, 95.7% (44/46) of genotype C and 64.0%
      (32/50) of genotype B samples were collected from Northern and Southern China,
      respectively. The accuracy of genotyping was confirmed by analyzing DNA sequences
      of 24 samples. It is demonstrated that low-density oligo microarray can serve as
      a reliable and time-saving method to HBV genotyping from patient's sera.

PMID- 16431079
TI  - A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD
      mouse.
AB  - Deficiencies in apoptotic cell clearance have been linked to autoimmunity. Here
      we examined the time-course of peritoneal macrophage phagocytosis of dying cells
      following the direct injection of apoptotic thymocytes into the peritoneum of NOD
      mice and BALB/c controls. Macrophages from NOD mice demonstrated a profound
      defect in the phagocytosis of apoptotic thymocytes as compared to control
      macrophages. Nonobese diabetic mice also demonstrated a decrease in the clearance
      of apoptotic cell loads following an apoptotic stimulus to thymocytes
      (dexamethasone) when compared to BALB/c or NOR controls. Further, NOD mice
      demonstrated an increase in apoptotic cell load following an apoptotic stimulus
      to keratinocytes (ultraviolet light, UVB) when compared to control strains.
      Animals deficient in macrophage phagocytosis of apoptotic debris often manifest
      an autoimmune phenotype characterized by the production of antinuclear
      autoantibodies (ANA). We determined whether increased apoptotic cell loads
      (through repeated exposure to UVB irradiation) could accelerate such autoimmune
      phenomena in young NOD mice. Following repeated UVB irradiation, NOD mice, but
      not BALB/c or NOR controls, developed ANA. We propose that abnormalities in
      apoptotic cell clearance by macrophages predispose NOD mice to autoimmunity.

PMID- 16431081
TI  - Increased expression of germinal center-associated nuclear protein (GANP) is
      associated with malignant transformation of melanocytes.
AB  - BACKGROUND: Germinal center-associated nuclear protein (GANP) is a newly cloned
      molecule that is up-regulated in the germinal center B cells. Although GANP
      functions in the regulation of DNA repair during replication and survival of B
      cells, little is known about its expression in melanocytic cells. OBJECTIVES: To
      investigate whether GANP and phosphorylated-GANP (P-GANP) are expressed in
      cultured human melanocytes and melanoma cells and in benign and malignant
      melanocytic lesions. In addition, we aim to determine whether GANP and P-GANP are
      associated with malignant transformation of melanocytic lineage. METHODS: GANP
      and P-GANP expression in cultured melanocytic cells was analyzed by
      immunostaining and in vitro kinase assay. GANP and P-GANP expression in
      melanocytic lesions was analyzed by immunohistochemistry. RESULTS: GANP and P
      GANP were up-regulated in cultured melanoma cells compared to melanocytes. GANP
      and P-GANP were restricted to nucleus of melanocytes but co-expressed in
      cytoplasm of melanoma cells. On the other hand, GANP and P-GANP were widely
      expressed at various levels in melanocytic nevi and melanoma lesions with nuclear
      and cytoplasmic staining pattern. Melanoma cells showed a stronger intensity of
      GANP and P-GANP than melanocytic nevus cells, however the staining intensity in
      primary melanoma lesions was not associated with any clinicopathological
      variables. Cytoplasmic GANP and P-GANP expression was associated with MCM3 and
      Ki67 expression. CONCLUSIONS: These data suggest, for the first time, that GANP
      and P-GANP are up-regulated in cultured melanoma cells compared to melanocytes
      and also they are widely expressed in benign and malignant melanocytic tumor
      cells.

PMID- 16431080
TI  - Characterization and function of MYPT2, a target subunit of myosin phosphatase in
      heart.
AB  - Characterization of cardiac MYPT2 (an isoform of the smooth muscle phosphatase
      [MP] target subunit, MYPT1) is described. Several features of MYPT2 and MYPT1
      were similar, including: a specific interaction with the catalytic subunit of
      type 1 phosphatase, delta isoform (PP1cdelta); interaction of MYPT2 with the
      small heart-specific MP subunit; interaction of the C-terminal region of MYPT2
      with the active form of RhoA; phosphorylation by Rho-kinase at an inhibitory
      site, Thr646 and thiophosphorylation at Thr646 inhibited activity of the MYPT2
      PP1cdelta complex. MYPT2 activated PP1cdelta activity, using light chains from
      smooth and cardiac muscle, by reducing K(m) and increasing k(cat). The extent of
      activation (k(cat)) was greater than for MYPT1 and could reflect distinct N
      terminal sequences in the two MYPT isoforms. Adenovirus-mediated gene transfer of
      MYPT2 and PP1cdelta reduced the phosphorylation level of cardiac light chains
      following stimulation with A23187. Overexpression of MYPT2 and PP1cdelta blocked
      the angiotensin II-induced sarcomere organization in cultured cardiomyocytes.
      Electron microscopy indicated locations of MYPTs, at, or close to, the Z-line,
      the A band and mitochondria. Similarity of the two MYPT isoforms suggests common
      enzymatic mechanisms and regulation. Cardiac myosin is a substrate for the MYPT2
      holoenzyme, but the Z-line location raises the possibility of other substrates.

PMID- 16431082
TI  - Nadifloxacin downmodulates antigen-presenting functions of epidermal Langerhans
      cells and keratinocytes.
AB  - BACKGROUND: Nadifloxacin is an anti-microbial quinolone derivative widely used
      for the treatment of acne as a topical agent. This drug has been suggested to
      have not only anti-bacterial but also anti-inflammatory actions, which may have a
      beneficial effect on some aspects of inflammatory acne. OBJECTIVE: To further
      clarify its abilities to modulate skin immunity, we investigated whether
      nadifloxacin affects the hapten- and superantigen-presenting capacities of
      epidermal Langerhans cells (LC) and keratinocytes, respectively. METHODS: Immune
      lymph node CD4+ T cells from trinitrophenyl-sensitized BALB/c mice were
      cocultured with LC-enriched epidermal cells (LC-EC) that were freshly isolated
      from syngeneic mice and derivatized with trinitrophenyl hapten in the presence or
      absence of nadifloxacin. Alternatively, LC-EC were preincubated with nadifloxacin
      (NDFX), modified with the hapten, and cultured with immune T cells. The effects
      of nadifloxacin on the surface molecule expression in LC and keratinocytes were
      also tested by flow cytometry and cellular ELISA. RESULTS: LC-EC cultured with
      nadifloxacin at 10 microg/ml or more significantly suppressed the antigen
      presenting function of LC for T cells. The ability of MHC class II+ keratinocytes
      to present a superantigen to T cells was suppressed by preincubation of
      keratinocytes with 30 microg/ml or more of nadifloxacin. These functional
      reductions in LC and keratinocytes reflected the decreased expression of MHC
      class II and/or costimulatory molecules. CONCLUSION: Nadifloxacin downmodulates
      cutaneous immunity by interfering with the antigen-presenting ability of
      epidermal cells.

PMID- 16431083
TI  - The microbiology of spacecraft hardware: lessons learned from the planetary
      protection activities on the Beagle 2 spacecraft.
AB  - We consider the aseptic assembly of the Beagle 2 Mars probe and how the
      requirements of COSPAR planetary protection category IVa were achieved. Several
      areas for future investigation became apparent. An ESA mission is outlined in
      which a microbial bioburden is recovered after Earth orbit to assess viability
      following re-entry through the atmosphere.

PMID- 16431084
TI  - The SOS-LUX-TOXICITY-Test on the International Space Station.
AB  - For the safety of astronauts and to ensure the stability and integrity of the
      genome of microorganisms and plants used in bioregenerative life support systems,
      it is important to improve our knowledge of the combined action of (space)
      radiation and microgravity. The SOS-LUX-TOXICITY test, as part of the TRIPLE-LUX
      project (accepted for flight at Biolab in Columbus on the International Space
      Station, (ISS)), will provide an estimation of the health risk resulting from
      exposure of astronauts to the radiation environment of space in microgravity. The
      project will: (i) increase our knowledge of biological/health threatening action
      of space radiation and enzymatic DNA repair; (ii) uncover cellular mechanisms of
      synergistic interaction of microgravity and space radiation; (iii) provide
      specified biosensors for spacecraft milieu examination; and (iv) provide
      experimental data on stability and integrity of bacterial DNA in spacecrafts. In
      the bacterial biosensor "SOS-LUX-Test" developed at DLR (patent), bacteria are
      transformed with the pBR322-derived plasmid pPLS-1 or the similar, advanced
      plasmid SWITCH, both carrying the promoterless lux operon of Photobacterium
      leiognathi as the reporter element controlled by a DNA damage-dependent SOS
      promoter as sensor element. A short description of the space experiment is given,
      and the current status of adaptation of the SOS-LUX-Test to the ISS, i.e. first
      results of sterilization, biocompatibility and functional tests performed with
      the already available hardware and bread board model of the automated space
      hardware under development, is described here.

PMID- 16431085
TI  - A minimal estimate for the gene content of the last universal common ancestor-
      exobiology from a terrestrial perspective.
AB  - Using an algorithm for ancestral state inference of gene content, given a large
      number of extant genome sequences and a phylogenetic tree, we aim to reconstruct
      the gene content of the last universal common ancestor (LUCA), a hypothetical
      life form that presumably was the progenitor of the three domains of life. The
      method allows for gene loss, previously found to be a major factor in shaping
      gene content, and thus the estimate of LUCA's gene content appears to be
      substantially higher than that proposed previously, with a typical number of over
      1000 gene families, of which more than 90% are also functionally characterized.
      More precisely, when only prokaryotes are considered, the number varies between
      1006 and 1189 gene families while when eukaryotes are also included, this number
      increases to between 1344 and 1529 families depending on the underlying
      phylogenetic tree. Therefore, the common belief that the hypothetical genome of
      LUCA should resemble those of the smallest extant genomes of obligate parasites
      is not supported by recent advances in computational genomics. Instead, a fairly
      complex genome similar to those of free-living prokaryotes, with a variety of
      functional capabilities including metabolic transformation, information
      processing, membrane/transport proteins and complex regulation, shared between
      the three domains of life, emerges as the most likely progenitor of life on
      Earth, with profound repercussions for planetary exploration and exobiology.

PMID- 16431086
TI  - Atmospheric entry simulations of Mars lander bioload--experiments in support of
      Beagle 2.
AB  - Simulations of the temperature and vacuum effects of Martian atmospheric entry
      upon Bacillus atrophaeus (formerly Bacillus subtilis var niger; 8058; NCIMB)
      endospores were carried out inside a purpose-built vacuum chamber. The work
      formed part of the study in support of planetary protection for the Beagle 2 Mars
      lander and investigated to what extent the outer surface of the lander's back
      heat shield would be sterilised during Mars atmospheric entry. The spores were
      heated to peak temperatures up to 300 degrees C over 30 s under vacuum conditions
      (10(-3) mbar). There was no effect on spore viability until peak temperatures
      reached 180-200 degrees C (12-15 s of heat exposure). Spore viability then fell
      rapidly with increasing temperature. Once peak temperatures exceeded 300 degrees
      C, no further spore viability was detected. The average heating rate was rapid
      (10 degrees C s(-1)); thus spores were exposed to peak temperatures for less than
      a second. These data inform on the process of determining bioburden reduction and
      control steps necessary for external surfaces of spacecraft which are non-sterile
      at launch, as well as providing new information about the ability of a model
      resistant organism to survive rapid, short-duration heating.

PMID- 16431087
TI  - Extracellular polymeric substances mediate bioleaching/biocorrosion via
      interfacial processes involving iron(III) ions and acidophilic bacteria.
AB  - Extracellular polymeric substances seem to play a pivotal role in biocorrosion of
      metals and bioleaching, biocorrosion of metal sulfides for the winning of
      precious metals as well as acid rock drainage. For better control of both
      processes, the structure and function of extracellular polymeric substances of
      corrosion-causing or leaching bacteria are of crucial importance. Our research
      focused on the extremophilic bacteria Acidithiobacillus ferrooxidans and
      Leptospirillum ferrooxidans, because of the "simplicity" and knowledge about the
      interactions of these bacteria with their substrate/substratum and their
      environment. For this purpose, the composition of the corresponding extracellular
      polymeric substances and their functions were analyzed. The extracellular
      polymeric substances of both species consist mainly of neutral sugars and lipids.
      The functions of the exopolymers seem to be: (i) to mediate attachment to a
      (metal) sulfide surface, and (ii) to concentrate iron(III) ions by complexation
      through uronic acids or other residues at the mineral surface, thus, allowing an
      oxidative attack on the sulfide. Consequently, dissolution of the metal sulfide
      is enhanced, which may result in an acceleration of 20- to 100-fold of the
      bioleaching process over chemical leaching. Experiments were performed to
      elucidate the importance of the iron(III) ions complexed by extracellular
      polymeric substances for strain-specific differences in oxidative activity for
      pyrite. Strains of A. ferrooxidans with a high amount of iron(III) ions in their
      extracellular polymeric substances possess greater oxidation activity than those
      with fewer iron(III) ions. These data provide insight into the function of and
      consequently the advantages that extracellular polymeric substances provide to
      bacteria. The role of extracellular polymeric substances for attachment under the
      conditions of a space station and resulting effects like biofouling,
      biocorrosion, malodorous gases, etc. will be discussed.

PMID- 16431088
TI  - The European standard on planetary protection requirements.
AB  - Since the beginning of solar system exploration, numerous spacecrafts have been
      sent towards others worlds, and one of the main goals of such missions is the
      search for extraterrestrial forms of life. It is known that, under certain
      conditions, some terrestrial entities are able to survive during cruises in space
      and that they may contaminate other planets (forward contamination). At another
      level, possible extraterrestrial life forms are unknown and their ability to
      contaminate the Earth's biosphere (back contamination) in the frame of sample
      return missions cannot be excluded. Article IX of the Outer Space Treaty
      (London/Washington, January 27, 1967) requires the preservation of planets and
      the Earth from contamination. All nations taking part in this Treaty must prevent
      forward and back contamination during missions exploring our solar system.
      Consequently, the United Nations (UN-COPUOS) has delegated COSPAR (Committee of
      Space Research) to take charge of planetary protection and, at present, all space
      faring nations must comply with COSPAR policy and consequently with COSPAR
      planetary protection recommendations. Starting from these recommendations and the
      "CNES Planetary Protection Standard" document, a working group has been set up in
      the framework of the "European Cooperation for Space Standardization" (ECSS) to
      establish the main specifications for preventing cross-contamination between
      target bodies within the solar system and the Earth-moon system.

PMID- 16431090
TI  - Proceedings of the 3rd International Workshop on Space Microbiology, 22-25 May
      2005, Mol, Belgium.

PMID- 16431089
TI  - Microbial ecology of the closed artificial ecosystem MELiSSA (Micro-Ecological
      Life Support System Alternative): reinventing and compartmentalizing the Earth's
      food and oxygen regeneration system for long-haul space exploration missions.
AB  - MELiSSA is a bioregenerative life support system designed by the European Space
      Agency (ESA) for the complete recycling of gas, liquid and solid wastes during
      long distance space exploration. The system uses the combined activity of
      different living organisms: microbial cultures in bioreactors, a plant
      compartment and a human crew. In this minireview, the development of a short-cut
      ecological system for the biotransformation of organic waste is discussed from a
      microorganism's perspective. The artificial ecological model--still in full
      development--that is inspired by Earth's own geomicrobiological ecosystem serves
      as an ideal study object on microbial ecology and will become an indispensable
      travel companion in manned space exploration.

PMID- 16431091
TI  - Characterization of the serotonin transporter in lymphocytes and platelets of
      schizophrenia patients treated with atypical or typical antipsychotics compared
      to healthy individuals.
AB  - A rapidly growing body of data suggests that abnormalities in serotonergic
      function might be involved in the pathophysiology of schizophrenia and that
      serotonergic mechanisms play a role in the therapeutic effects of antipsychotics.
      The activity of the serotonin transporter (5-HTT), as determined by [(3)H]5-HT
      uptake to blood lymphocytes, was measured in 38 medicated schizophrenia patients
      (15 of them treated with typical antipsychotics and 23 treated with atypical
      antipsychotics) and 15 healthy control subjects. In addition, the pharmacodynamic
      characteristics of platelet 5-HTT were assessed by [(3)H]citalopram binding.
      There were no significant differences in the density (B(max)) of platelet
      [(3)H]citalopram binding sites between the three groups. Similarly, the
      dissociation constant (K(d)) values were indistinguishable. There were no
      significant differences in the maximal uptake velocity (V(max)) of [(3)H]5-HT to
      fresh lymphocytes between the three groups. The affinity (K(m)) values of 5-HT to
      the 5-HTT were significantly higher in schizophrenia patients treated with
      typical antipsychotics compared with control subjects. The K(m) values in
      schizophrenia patients treated with atypical antipsychotics were significantly
      lower compared with those observed in the group of schizophrenia patients treated
      with typical antipsychotics; however, they were comparable to values in the
      control group. The high values of K(m) associated with typical antipsychotic
      treatment may be relevant to the high risk of developing extrapyramidal side
      effects (EPS). The role of the various components of the serotonergic system in
      the etiopathology of schizophrenia and the mechanisms by which antipsychotics
      achieve their therapeutic effects need to be further evaluated.

PMID- 16431092
TI  - In vivo contribution of Class III alcohol dehydrogenase (ADH3) to alcohol
      metabolism through activation by cytoplasmic solution hydrophobicity.
AB  - Alcohol metabolism in vivo cannot be explained solely by the action of the
      classical alcohol dehydrogenase, Class I ADH (ADH1). Over the past three decades,
      attempts to identify the metabolizing enzymes responsible for the ADH1
      independent pathway have focused on the microsomal ethanol oxidizing system
      (MEOS) and catalase, but have failed to clarify their roles in systemic alcohol
      metabolism. In this study, we used Adh3-null mutant mice to demonstrate that
      Class III ADH (ADH3), a ubiquitous enzyme of ancient origin, contributes to
      alcohol metabolism in vivo dose-dependently resulting in a diminution of acute
      alcohol intoxication. Although the ethanol oxidation activity of ADH3 in vitro is
      low due to its very high Km, it was found to exhibit a markedly enhanced
      catalytic efficiency (kcat/Km) toward ethanol when the solution hydrophobicity of
      the reaction medium was increased with a hydrophobic substance. Confocal laser
      scanning microscopy with Nile red as a hydrophobic probe revealed a cytoplasmic
      solution of mouse liver cells to be much more hydrophobic than the buffer
      solution used for in vitro experiments. So, the in vivo contribution of high-Km
      ADH3 to alcohol metabolism is likely to involve activation in a hydrophobic
      solution. Thus, the present study demonstrated that ADH3 plays an important role
      in systemic ethanol metabolism at higher levels of blood ethanol through
      activation by cytoplasmic solution hydrophobicity.

PMID- 16431093
TI  - The halotolerant fungus Glomerobolus gelineus is a member of the Ostropales.
AB  - Glomerobolus gelineus is a halotolerant species with a unique method of ballistic
      propagation. The absence of both sexual and asexual spores made reliable
      placement of this species, based on morphology alone, within the current fungal
      classification problematical. A phylogenetic analysis of the large and small
      nuclear ribosomal subunit and the second largest subunit of RNA polymerase II
      placed this fungus within the Ostropales, an order comprising lichenized and
      saprobic species, with good statistical support. Subsequently, a more detailed
      analysis that combined the nuc LSU rDNA and the mt SSU rDNA confirmed a close
      relationship to the Stictidaceae. The phylogenetic placement of G. gelineus is
      also supported by morphological characters. We postulate that the hyphoma lobes
      of Glomerobolus correspond to the periphysoidal layer in the apothecium of
      Stictis, and the propagule to the hymenium. Moreover, the presence of crystals in
      the outer lobes of G. gelineus is another indication of its relationship with
      Ostropales, which have characteristic crystalliferous hyphae. The placement of
      Glomerobolus within the Ostropales further expands the ecological diversity
      exhibited by this order. It also provides a phylogenetic hypothesis for assessing
      the homology of the enigmatic hyphomal morphology with apothecia-forming
      Ascomycota.

PMID- 16431094
TI  - Genetic diversity in the blackberry rust pathogen, Phragmidium violaceum, in
      Europe and Australasia as revealed by analysis of SAMPL.
AB  - Indigenous to Europe, the blackberry rust fungus Phragmidium violaceum was
      introduced to Australia and subsequently appeared in New Zealand, with the most
      recent authorised introductions to Australia specifically for the biological
      control of European blackberry. Markers for 'selective amplification of
      microsatellite polymorphic loci' (SAMPL) were developed for studying the
      population genetics of P. violaceum. Modification of one of the two SAMPL primers
      with a HaeIII adapter (H) revealed significantly greater levels of genetic
      variation than primers used to generate AFLPs, the latter revealing little or no
      variation among 25 Australasian and 19 European isolates of P. violaceum. SAMPL
      was used to describe genetic variation among these 44 isolates of P. violaceum
      from 51 loci generated using primer pairs (GACA)4 +H-G and R1+H-G. The European
      isolates were more diverse than Australasian isolates, with 37 and 22 %
      polymorphic loci, respectively. Cluster analysis revealed geographic clades, with
      Australasian isolates forming one cluster separated from two clusters comprising
      the European isolates. However, low bootstrap support at these clades suggested
      that Australian isolates had not differentiated significantly from European
      isolates since the first record of P. violaceum in Australia in 1984. In general,
      the results support two hypotheses. First, that the population of P. violaceum in
      Australia was founded from a subset of individuals originating from Europe.
      Second, that P. violaceum in New Zealand originated from the Australian
      population of P. violaceum, probably by wind dispersal of urediniospores across
      the Tasman Sea. The application of SAMPL markers to the current biological
      control programme for European blackberry is discussed.

PMID- 16431095
TI  - A comparison of exhaled nitric oxide measurements performed using three different
      analysers.
AB  - INTRODUCTION: Exhaled nitric oxide (NO) is an established technique for
      monitoring airway inflammation. We have compared exhaled NO measurements from 3
      different analysers; Ecomedics (E), Niox (N) and Logan (L). METHODS: Thirty
      subjects (10 non-smoking healthy subjects, 10 non-smoking patients with asthma
      and 10 ex-smoking COPD patients) performed 3 repeated measurements of exhaled NO
      at a flow rate of 50 ml/s on each of the 3 analysers. Within analyser variability
      was determined by calculating the repeatability coefficient for each analyser.
      Differences between analysers were assessed by (1) the differences between group
      means and (2) the Bland Altman method to estimate the variability expected for an
      individual using the 3 analysers. RESULTS: The repeatability coefficients
      (expressed as ratios) were 1.12, 1.19 and 1.19 for N, E and L, respectively.
      There were significant differences (P<0.05) between analysers; the Logan analyser
      gave the highest group mean values and Ecomedics gave the lowest group mean
      values. Differences between analysers were observed in all subject groups
      (healthy, asthma, COPD). Similar results were obtained in the 3 groups when
      analysed separately. Bland Altman analysis gave the following ratios [data are
      mean ratio (95% limits of agreement)]; N:E 1.59 (1.02-2.50), L:N 1.23 (0.72
      2.13), L:E 1.96 (1.09-3.57). CONCLUSION: Our findings indicate that exhaled NO
      measurements in healthy subjects and patients with airways disease differ
      according to the type of analyser used.

PMID- 16431096
TI  - Lightweight aggregate made from sewage sludge and incinerated ash.
AB  - In this study, sewage sludge ash (SSA), with similar characteristics to expansive
      clay, was used as the principal material and sewage sludge (SS) as the admixture
      to sinter lightweight aggregate and to study the influences of raw material
      composition on pelletising, sintering effect and aggregate properties. Results
      showed that both SS and SSA could be sintered to produce synthetic aggregates
      individually or mixed. Increasing the amount of SS would decrease the pelletising
      ratio. Under the consideration of energy saving, the mixture of SSA was better
      for sintering normal weight aggregate. On the contrary, the mixture that added 20
      30% of SS was more adequate to make lightweight aggregates. Adding SS would
      enhance the oxidation-reduction reaction and lower the bulk density and sintering
      temperature of aggregates to save energy. Sintering temperature affected the
      properties of sewage sludge ash lightweight aggregate (SSALA) more than retention
      period did. Prolonging the retention period could improve bloating effect.

PMID- 16431097
TI  - Manometric transduction in enzyme biosensors.
AB  - The combination of enzymatic recognition and manometric transduction is explored,
      using enzymes that consume or evolve a gas with low solubility in aqueous media.
      A design is discussed whereby change in partial pressure of a gas in the
      headspace is related to the turnover of analyte by the enzyme. Headspace and
      sample volume dimensions are considered, demonstrating the influence of flux at
      the air-water interface. The relative importance of diffusion and reaction for
      the enzyme solution is shown. When enzyme kinetics dominate, the concentration
      gradient is low and the overall kinetics are determined by the total amount of
      active enzyme, reducing either enzyme concentration or enzyme layer thickness
      will reduce the diffusion limitation. A Teflon-enzyme composite is presented to
      allow a reuseable immobilised enzyme preparation and a disc with stirring magnet
      identified as an efficient configuration. A glucose oxidase system was tested in
      the monitoring of glucose consumption during fermentation. Application to other
      enzyme systems is discussed.

PMID- 16431098
TI  - Simultaneous determination of kinetic parameters for the binding of cholera toxin
      to immobilized sialic acid and monoclonal antibody using an array biosensor.
AB  - Interactions between protein toxins and carbohydrate receptors are often semi
      selective processes and the kinetic parameters that define the binding of a
      receptor to different toxins may vary with each interaction. In this study, we
      have determined the affinity constants for binding of cholera toxin (CT) to
      immobilized sialic acid and to anti-CT antibody (as a simultaneous reference) by
      measuring real-time binding processes using an array biosensor. N
      Acetylneuraminic acid (Neu5Ac), a member of the sialic acid family, was
      covalently immobilized onto maleimide-activated planar waveguides via a thiol
      terminated linker attached to the anomeric carbon of the sugar. Control
      antibodies were immobilized using two different approaches: covalent attachment
      onto maleimide-activated slides via the thiol on cysteine residues and non
      covalent attachment using a biotin-NeutrAvidin linkage. Cy5-labeled CT was flowed
      over the immobilized receptors and the fluorescent intensity of the bound CT
      receptor complex was recorded as a function of time. The association constants
      for CT binding to covalently attached Neu5Ac, to covalently attached anti-CT
      monoclonal antibody, and to antibody tethered by biotin-NeutrAvidin interactions
      were determined to be 1.3 x 10(8), 2.1 x 10(8) and 5.7 x 10(8)M(-1),
      respectively.

PMID- 16431099
TI  - A novel estrogen sensor based on recombinant Arxula adeninivorans cells.
AB  - A novel yeast cell-based assay was developed for the detection of estrogenic
      activity in wastewater. Recombinant Arxula adeninivorans strains were engineered
      to co-express the human estrogen receptor alpha (hERalpha) and a Klebsiella
      derived phytase (phyK) reporter gene under the control of an A. adeninivorans
      derived glucoamylase (GAA) promoter which had been modified by the insertion of
      estrogen-responsive elements (EREs). In the presence of estrogenic compounds,
      hERalpha dimerizes and binds to the estrogen. Reporter gene expression is induced
      by subsequent binding of the hERalpha-dimer/estrogen complex to estrogen
      responsive elements (ERE) in the promoter. The insertion of different numbers of
      EREs in three alternative promoter positions and its effect on reporter gene
      expression were assessed. In one of the constructs, a detection limit of 5 ng l(
      1) and a determination limit of 10 ng l(-1) for 17beta-estradiol-like activity
      was achieved. The photometric assay used enabled estrogen determination in sewage
      samples within 30 h.

PMID- 16431100
TI  - Coronary arterial air embolus occurring during cesarean delivery.
AB  - We present a case of a severe systemic (paradoxical) air embolism occurring
      during spinal anesthesia for cesarean delivery in an otherwise healthy 35-year
      old parturient. Uncomplicated spinal anesthesia and satisfactory surgical
      anesthesia were obtained; no sedatives were used and the patient was awake and
      alert and tolerating the procedure well. Immediately following infant and
      placental delivery (approximately 25 min after the spinal anesthetic was induced)
      the patient had acute onset of markedly decreased mental status, profound
      ventricular ectopy and labile blood pressure. The event lasted for approximately
      10 min with spontaneous resolution. Neurologic status returned to normal by the
      end of the surgery, but electrocardiogram findings in the immediate postoperative
      period were consistent with myocardial ischemia and serial cardiac troponin
      levels confirmed myocardial injury. On postoperative day 1, an echocardiogram
      demonstrated the presence of a patent foramen ovale. The events in this case are
      likely to be due to paradoxical coronary and cerebral air embolism.

PMID- 16431102
TI  - Hypertrophic cardiomyopathy and caesarean section: intraoperative use of
      transthoracic echocardiography.
AB  - A pregnant woman with severe hypertrophic cardiomyopathy was monitored with
      transthoracic echocardiography to guide management of fluids and vasopressors
      during elective caesarean section. After insertion of intravenous, arterial and
      central venous cannulae, a transthoracic echocardiogram was performed noting left
      ventricular cavity size and contractility, systolic anterior motion of the mitral
      valve and left ventricular outflow tract obstruction. Following combined spinal
      epidural anaesthesia, serial examinations were made intraoperatively. Short-lived
      haemodynamic instability ensued just before the incision and with administration
      of oxytocin. Her postoperative course was complicated by post-partum haemorrhage
      requiring radiological intervention but she ultimately recovered fully.
      Maintaining preload to avoid worsening of left ventricular outflow tract
      obstruction is essential in these patients. A transthoracic echocardiogram is
      easily performed, of low risk and provides more useful information than a
      pulmonary artery catheter.

PMID- 16431101
TI  - Meningitis following intrathecal catheter placement after accidental dural
      puncture.

PMID- 16431103
TI  - On knots in epidural catheters: a case report and a review of the literature.
AB  - A lumbar epidural catheter placed for labor analgesia proved to be difficult to
      remove after an uneventful delivery. With the patient in the position of catheter
      insertion, i.e. seated, firm and steady traction allowed removal of the catheter
      and revealed a knot 4 mm from its tip. Passing excessive amount of catheter into
      the epidural space may have contributed to this complication. Guidelines to
      prevent and to minimize this complication are suggested.

PMID- 16431105
TI  - 131st ENMC international workshop: selection of outcome measures for peripheral
      neuropathy clinical trials 10-12 December 2004, Naarden, The Netherlands.

PMID- 16431104
TI  - High-throughput techniques in breast cancer: a clinical perspective.
AB  - High-throughput technologies such as DNA-microarrays, RT-PCR and proteomics can
      improve the prognostic and predictive information acquired from classical
      parameters. Unlike information gathered by classical methods, high-throughput
      technologies can accurately inform clinicians on patient response to adjuvant
      therapy or those who will resist the effect of that therapy. Studies performed in
      breast cancer with high-throughput techniques have focused on tumour biology,
      prognosis, prediction of response to a few agents and, more recently, early
      diagnosis. However, further refinement is needed before these techniques become
      part of clinical routine. In the meantime, they will be used in clinical
      investigation, particularly in the areas of hormonal therapy and adjuvant
      chemotherapy, where modest improvements in the capacity of prediction can benefit
      many women. Close cooperation among clinicians, pathologists and basic
      investigators is essential to take high-throughput techniques to daily practice.
      New diagnostic tools will be complex but they will provide valuable patient
      information.

PMID- 16431106
TI  - Comparison between visual and three-dimensional gait analysis in patients with
      spastic diplegic cerebral palsy.
AB  - Fifty patients with spastic diplegic cerebral palsy were included in this
      retrospective study which compared visual assessment of gait to three-dimensional
      (3D) gait analysis. Inter-observer variability was evaluated as well. Inclusion
      criteria comprehended independent ambulation (i.e. without assistive devices or
      orthoses). All subjects went through 3D gait analysis at the Gait Analysis
      Laboratory of the AACD Hospital. Four observers, viewing videotaped gait cycles,
      evaluated 10 specific points of interest of the cycle: hip flexion at terminal
      stance; knee flexion at initial contact; knee extension at terminal stance; knee
      flexion at initial swing; ankle dorsiflexion at initial contact; pelvic obliquity
      at mid stance; hip adduction at loading response; pelvic rotation; hip rotation
      at mid stance and foot progression angle, in relation to the lower limb, at mid
      stance. Their evaluation was then compared to the 3D kinematics data. A
      statistical analysis of the results was performed using kappa and McNemar's test
      in order to determine inter-observer and visual/3D analysis agreement. Results
      showed that inter-observer agreement was high but on the other hand, only two
      points of the gait cycle (knee flexion at initial contact and pelvic obliquity)
      were shown to have been similarly evaluated visually and with the 3D analysis. In
      conclusion, this study indicates that only knee flexion at initial contact and
      pelvic obliquity appear to be reliably evaluated on a visual basis alone. Visual
      observation is therefore inadequate for the evaluation of the other eight
      selected points of the gait cycle which require some form of quantitative
      assessment.

PMID- 16431107
TI  - Don't forget cortical Lewy bodies.

PMID- 16431108
TI  - Leptomeningeal infiltration as the presenting manifestation of a malignant
      glioma.
AB  - Infiltration of the leptomeninges by a malignant glioma typically occurs with
      recurrent supratentorial tumors, but patients may present with leptomeningeal
      gliomatosis before the primary tumor is diagnosed. This report describes two
      patients who presented with headache and signs of multifocal neurological
      disease. One of the patients had neurofibromatosis type I. In both patients the
      cerebrospinal fluid examination showed a mild pleocytosis, but malignant cells
      were not detected. The diagnosis of leptomeningeal gliomatosis was not confirmed
      until autopsy, but in retrospect imaging showed a small, asymptomatic primary
      tumor in both patients. Leptomeningeal gliomatosis should be considered in the
      differential diagnosis of chronic meningitis, if the patient is afebrile and if
      there are multifocal neurological signs, even when a primary tumor is not
      obvious.

PMID- 16431109
TI  - Epidermoid tumor arising in the anterior interhemispheric fissure.
AB  - There have only been 18 cases reported in the literature of an epidermoid tumor
      arising in the interhemispheric fissure. We report a 45-year-old woman with an
      epidermoid tumor arising in the interhemispheric fissure. She presented with a
      focal convulsive seizure. Radiological imaging identified a tumor in the
      interhemispheric fissure, which was subtotally removed due to adherence to both
      anterior cerebral arteries and the cerebral cortex. Epidermoid tumor was
      confirmed by histopathology. Epidermoid tumors rarely arise in the
      interhemispheric fissure, but are often adherent to surrounding structures and
      thus, as in the presented case, complete resection may be unwise.

PMID- 16431110
TI  - Rhabdomyolysis after cerebral perfusion pressure-guided management in severe head
      injury.
AB  - Intravenous infusion of norepinephrine is usually effective and safe to maintain
      adequate cerebral perfusion pressure for the management of posttraumatic
      intracranial hypertension. We report the case of a 17-year-old woman who suffered
      from traumatic intracranial bleeding and hypotension; she developed
      rhabdomyolysis, myoglobinuria and acute renal failure after receiving high dose
      norepinephrine postoperatively. Hemodialysis was begun 3 days after the onset of
      myoglobinuria when acute renal failure was noted, despite aggressive fluid
      supplementation and alkaline diuresis. After aggressive treatment and dialysis,
      the patient's myoglobinuria and rhabdomyolysis gradually declined. Her kidneys
      eventually regained normal function. We consider that systemic hypotension may
      have been the leading cause for development of rhabdomyolysis, and
      vasoconstrictors such as norepinephrine aggravated this. We emphasise the
      potentially devastating consequences of rhabdomyolysis when a large dose of
      norepinephrine is given for the treatment of hypotension during cerebral
      perfusion pressure-guided management.

PMID- 16431111
TI  - QSAR modeling of mono- and bis-quaternary ammonium salts that act as antagonists
      at neuronal nicotinic acetylcholine receptors mediating dopamine release.
AB  - Back-propagation artificial neural networks (ANNs) were trained on a dataset of
      42 molecules with quantitative IC50 values to model structure-activity
      relationships of mono- and bis-quaternary ammonium salts as antagonists at
      neuronal nicotinic acetylcholine receptors (nAChR) mediating nicotine-evoked
      dopamine release. The ANN QSAR models produced a reasonable level of correlation
      between experimental and calculated log(1/IC50) (r2=0.76, r(cv)2=0.64). An
      external test for the models was performed on a dataset of 18 molecules with IC50
      values >1 microM. Fourteen of these were correctly classified. Classification
      ability of various models, including self-organizing maps (SOM), for all 60
      molecules was also evaluated. A detailed analysis of the modeling results
      revealed the following relative contributions of the used descriptors to the
      trained ANN QSAR model: approximately 44.0% from the length of the N-alkyl chain
      attached to the quaternary ammonium head group, approximately 20.0% from
      Moriguchi octanol-water partition coefficient of the molecule, approximately
      13.0% from molecular surface area, approximately 12.6% from the first component
      shape directional WHIM index/unweighted, approximately 7.8% from Ghose-Crippen
      molar refractivity, and 2.6% from the lowest unoccupied molecular orbital energy.
      The ANN QSAR models were also evaluated using a set of 13 newly synthesized
      compounds (11 biologically active antagonists and two biologically inactive
      compounds) whose structures had not been previously utilized in the training set.
      Twelve among 13 compounds were predicted to be active which further supports the
      robustness of the trained models. Other insights from modeling include a
      structural modification in the bis-quinolinium series that involved replacing the
      5 and/or 8 as well as the 5' and/or 8' carbon atoms with nitrogen atoms,
      predicting inactive compounds. Such data can be effectively used to reduce
      synthetic and in vitro screening activities by eliminating compounds of predicted
      low activity from the pool of candidate molecules for synthesis. The application
      of the ANN QSAR model has led to the successful discovery of six new compounds in
      this study with experimental IC50 values of less than 0.1 microM at nAChR
      subtypes responsible for mediating nicotine-evoked dopamine release,
      demonstrating that the ANN QSAR model is a valuable aid to drug discovery.

PMID- 16431112
TI  - Design, synthesis, and biological testing of potential heme-coordinating nitric
      oxide synthase inhibitors.
AB  - Based on computer modeling of the active site of nitric oxide synthases (NOS), a
      series of 10 amidine compounds (9-18) was designed including potential inhibitors
      that involve the coordination of side-chain functional groups with the iron of
      the heme cofactor. The most potent and selective compound was the methylthio
      amidine analogue 9, which was more potent than L-nitroarginine with 185-fold
      selectivity for inhibition of neuronal NOS over endothelial NOS. It also
      exhibited time-dependent inhibition, but did not involve the mechanism previously
      proposed for other amidine inhibitors of NOS. None of the compounds, however,
      exhibited heme-binding characteristics according to absorption spectroscopy.

PMID- 16431113
TI  - Fragment-based drug discovery of carbonic anhydrase II inhibitors by dynamic
      combinatorial chemistry utilizing alkene cross metathesis.
AB  - A fragment-based drug discovery approach to the synthesis and identification of
      small molecule inhibitors of bovine carbonic anhydrase II (bCA II) is described.
      The classical bCA II recognition fragment is an aromatic sulfonamide (ArSO2NH2)
      moiety. This fragment was incorporated into a scaffold building block, which was
      subsequently derivatized by dynamic combinatorial chemistry utilizing alkene
      cross metathesis as the reversible reaction. Screening against bCA II was then
      carried out and the results allowed determination of the relative bCA II binding
      affinities of the cross metathesis products that contained the ArSO2NH2 fragment.
      A bCA II competitive binding assay validated these results with a representative
      number of pure compounds. The results for screening, without prior isolation of
      the active constituent, were in full agreement with those obtained for
      equilibrium dissociation constants (K(i)'s) of pure compounds. Some of these
      compounds exhibited K(i)'s in the low nanomolar range. Heterogeneous catalysis
      was shown to be very effective in this drug discovery application of dynamic
      combinatorial chemistry.

PMID- 16431114
TI  - Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin, squamostolide,
      and their inhibitory action with bovine heart mitochondrial complex I.
AB  - A convergent stereoselective synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)
      rollicosin and squamostolide was accomplished via a Pd-catalyzed cross-coupling
      reaction. The inhibitory activity of these compounds was examined with bovine
      heart mitochondrial NADH-ubiquinone oxidoreductase. These compounds showed a
      remarkably weak inhibitory activity compared to ordinary acetogenins such as
      bullatacin. Our results indicate that to maintain potent inhibitory effect, the
      hydroxylated lactone cannot substitute for the hydroxylated mono- or bis-THF
      rings with a long alkyl chain that can be seen in ordinary acetogenins.

PMID- 16431115
TI  - Synthesis, in vitro pharmacology, and structure-activity relationships of 2
      aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as mGluR2
      antagonists.
AB  - Chemical modification of the bicyclo[3.1.0]hexane ring C-3 position led to the
      discovery of 3-alkoxy-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 3
      benzylthio-, and 3-benzylamino-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6
      dicarboxylic acid derivatives, metabotropic glutamate receptor 2 (mGluR2)
      antagonists. In particular, 3-(3,4-dichlorobenzyloxy)-2-aminobicyclo[3.1.0]hexane
      2,6-dicarboxylic acid (15ae), (1R,2S,5R,6R)-2-amino-3-(3,4-dichlorobenzylthio)-6
      fluorobicyclo[3.1.0]hexane-2,6-carboxylic acid (15at), and (1R,2S,5R,6R)-2-amino
      3-(N-(3,4-dichlorobenzylamino))-6-fluorobicyclo[3.1.0]hexane-2,6-carboxylic
      (15ba) showed high affinity for the mGluR2 receptor (15ae: K(i) = 2.51 nM, 15at:
      K(i) = 1.96 nM, and 15ba: K(i) = 3.29 nM) and potent antagonist activity for
      mGluR2 (15ae; IC50 = 34.21 nM, 15at; IC50 = 13.34 nM, and 15ba; IC50 = 35.96 nM).
      No significant agonist activity for mGluR2 was observed with 15ae, 15at, or 15ba.
      This paper reports on the synthesis, in vitro pharmacological profile, and
      structure-activity relationships (SARs) of 3-substituted-2
      aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid.

PMID- 16431116
TI  - A new phenanthrene with a spirolactone from Dendrobium chrysanthum and its anti
      inflammatory activities.
AB  - Investigation of phenolic patterns from the stems of Dendrobium chrysanthum by
      HPLC-PDA-MS has led to the isolation of a new phenanthrene derivative with a
      spirolactone ring, dendrochrysanene (1), that proved to suppress the mRNA level
      of TNF-alpha, IL8, IL10, and iNOS in murine peritoneal macrophages. The structure
      of 1 was characterized on the basis of various NMR (1H, 13C, 1H-1H COSY, HMQC,
      and HMBC), mass spectrometry, and X-ray crystal diffraction data.

PMID- 16431117
TI  - Interaction of chromium(III) complex of chiral binaphthyl tetradentate ligand
      with DNA.
AB  - Since conformation of the molecule plays a vital role in the activity of drug, we
      have investigated the DNA interaction of a chromium(III) complex with ligands in
      two conformations. Chromium(III) complexes derived from chiral binaphthyl Schiff
      base ligands, viz. R- and S-2,2'-bis(salicylideneamino) 1,1'-binaphthyl, have
      been synthesized and characterized by mass, IR, and electronic spectra. The
      interaction of these R- and S-binaphthyl Schiff base chromium(III) complexes with
      CT-DNA was investigated with the goal of examining whether the chirality has an
      influence on the chromium(III)-DNA binding properties. The difference in
      chirality of the ligand did not show any striking difference in binding
      properties. The binding constants for R and S conformers were estimated to be 18
      (+/-0.4) x 10(3) and 9.4 (+/-0.3) x 10(3) M(-1), respectively, through
      spectroscopic titrations. All the experimental results are suggestive that both
      the isomers are DNA groove binders. The results of steady-state as well as time
      resolved fluorescence experiments, however, suggest that the R conformer has
      restricted mobility when bound to DNA because it is more deeply buried in the
      groove of DNA compared to the S isomer.

PMID- 16431119
TI  - 1-Benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diols as novel affinity and
      photoaffinity probes for beta-adrenoceptor subtypes.
AB  - Trimetoquinol (TMQ, 1) is a potent non-selective beta-adrenoceptor (beta-AR)
      agonist possessing a tetrahydroisoquinoline (THI) structure. The binding site for
      1-trimethoxybenzyl group of 1, which distinguishes it from classical
      catecholamines, is unknown. Affinity and photoaffinity labeled compounds are good
      tools to determine the exact interaction between a ligand and a specific amino
      acid(s) in a receptor. In this study, we designed and synthesized a series of
      affinity 6, 12, 18, and photoaffinity 24, 29 labeled analogues of TMQ. All of
      these compounds were full agonists and demonstrated an equal or greater binding
      affinity and functional activity as compared to TMQ on beta1-, beta2-, and beta3
      AR. Washout experiments on Chinese hamster ovary (CHO) cells expressing hu beta2
      AR were helpful in identifying the isothiocyanate 18 and the azide 24 as very
      effective affinity and photoaffinity labels at this receptor subtype.

PMID- 16431118
TI  - Enzymatically stable 5' mRNA cap analogs: synthesis and binding studies with
      human DcpS decapping enzyme.
AB  - Four novel 5' mRNA cap analogs have been synthesized with one of the
      pyrophosphate bridge oxygen atoms of the triphosphate linkage replaced with a
      methylene group. The analogs were prepared via reaction of nucleoside
      phosphor/phosphon-1-imidazolidates with nucleoside phosphate/phosphonate in the
      presence of ZnCl2. Three of the new cap analogs are completely resistant to
      degradation by human DcpS, the enzyme responsible for hydrolysis of free cap
      resulting from 3' to 5' cellular mRNA decay. One of the new analogs has very high
      affinity for binding to human DcpS. Two of these analogs are Anti Reverse Cap
      Analogs which ensures that they are incorporated into mRNA chains exclusively in
      the correct orientation. These new cap analogs should be useful in a variety of
      biochemical studies, in the analysis of the cellular function of decapping
      enzymes, and as a basis for further development of modified cap analogs as
      potential anti-cancer and anti-parasite drugs.

PMID- 16431120
TI  - Controllable synthesis of polymerizable ester and amide prodrugs of acyclovir by
      enzyme in organic solvent.
AB  - A facile control of the acylation position at the primary hydroxyl and amino of
      acyclovir, respectively, was achieved and five polymerizable acyclovir prodrugs
      were synthesized. Various reaction conditions were studied in detail. Thus,
      lipase acrylic resin from Candida antarctica (CAL-B) in pyridine or acetone
      showed high chemo-selectivity toward the primary hydroxyl of acyclovir. However,
      lipase PS 'Amano' (PS) in DMSO selectively acylated the amino group. The
      selectivity of PS could be adjusted by changing reaction solvents. The acyclovir
      vinyl derivatives obtained would be important monomers used for the preparation
      of macromolecular nucleoside drugs.

PMID- 16431121
TI  - Reassessing the melatonin pharmacophore--enantiomeric resolution, pharmacological
      activity, structure analysis, and molecular modeling of a constrained chiral
      melatonin analogue.
AB  - 3-(Acetylaminomethyl)-2-(ethoxycarbonyl)-6-methoxy-1,3,4,5
      tetrahydrobenzo[cd]indole (2) is a rigid melatonin analogue that as a racemate
      displays about the same affinity and intrinsic activity of melatonin (1) in in
      vitro experiments. We report here the resolution of the racemate by preparative
      medium pressure liquid chromatography (MPLC) and the X-ray determination of the R
      absolute configuration of the (-)-enantiomer. The two enantiomers were separately
      tested as MT1 and MT2 ligands, and the (+)-(S)-2 showed a potency comparable to
      that of melatonin and about three orders of magnitude greater than that of its
      enantiomer. The information obtained by crystallographic analysis and NMR studies
      about the conformational preference for 2 and by the pharmacological
      characterization of (R)-2 and (S)-2 was employed in a molecular modeling study,
      aimed at reassessing the melatonin receptor pharmacophore model for agonist
      compounds. Chiral enantioselective agonists reported in the literature were also
      included in the study.

PMID- 16431122
TI  - A multi-component reaction to 5-cyanouracils: synthesis and mechanistic study.
AB  - Acetonitrile as a solvent, excess of primary amines as general bases, and a
      reflux condition make the multi-component reactions of (2-cyanoacetyl) carbamate
      1, ethyl orthoformate, and primary amines form 5-cyanouracils 4a-c feasibly.
      Mechanistic studies of the multi-component reaction were carried out by proton
      NMR spectrometer. Acetonitrile as a solvent makes the reaction of 1 with ethyl
      orthoformate produce E-ethyl (2-cyano-3-ethoxyacryloyl) carbamate E-2 without a
      catalyst of acetic anhydride. The reactions of E-2 with primary amines produce
      the corresponding Z-3a-c as the only stable isomers eventually in CDCl3 or CD3CN.
      General-base-catalyzed intramolecular cyclizations of Z-3a-c at a reflux
      condition in CD3CN generated the corresponding 5-cyanouracils 4a-c.

PMID- 16431124
TI  - Clinical trials design and treatment tailoring: general principles applied to
      breast cancer research.
AB  - Nowadays tailored therapy tends to replace standard cancer treatment approaches.
      Tailoring treatment is possible thanks to clinical trials results that identified
      subgroups of patients benefiting most from some treatments. Treatment can be
      tailored on the basis of specific clinical characteristics of the population or
      on the basis of predictive or prognostic markers. Finally treatment can be
      tailored for specific molecular targets. This evolution in cancer treatment has
      triggered the development of innovative trial designs to validate these new
      hypotheses. The real challenge of the next coming years resides in recruiting
      large number of patients from specific subgroups to validate tailored therapies.

PMID- 16431123
TI  - An integrated, temporal study of the behavioural, electrophysiological and
      neuropathological consequences of murine prion disease.
AB  - We have conducted an integrated study of ME7 prion disease by examining the
      electrophysiological and neuropathological features of hippocampal slices from
      behaviourally characterised C57Bl/6J mice 12, 14, 16, 18, 20 and 24 weeks after
      intracerebral micro-injection of ME7 or normal brain homogenate. We describe the
      pathogenesis of ME7 as a three-stage process. STAGE ONE: PrPSc deposition,
      synaptic pathology and abnormal synaptic plasticity. STAGE TWO: Onset of
      behavioural changes, exemplified by an increase in open-field activity,
      enhancement of the slow AHP and development of vacuolation. Membrane
      depolarisation is also an early feature, but its exact timing remains to be
      confirmed. STAGE THREE: Clinical disease, substantial neurodegeneration and
      further disruption of the action potential profile. We suggest that the
      mechanisms underlying the electrophysiological changes of Stages one and two may
      provide novel approaches to treatment of prion disease, and that those seen in
      Stage three may be relevant to neurodegenerative diseases more generally.

PMID- 16431125
TI  - Posttranscriptional regulation of TNFalpha expression via eukaryotic initiation
      factor 4E (eIF4E) phosphorylation in mouse macrophages.
AB  - Resident mouse macrophages secrete Tumor necrosis factor alpha (TNFalpha) upon
      challenge with LPS. The production of TNFalpha is controlled not only at the
      transcription of the gene, but also by strong posttranscriptional regulation.
      When macrophages are stimulated with LPS different signal transduction pathways
      become activated. Here we show that the combination of the 2 kinases p38 and MEK
      and presumably ERK1/2 regulate translation of TNFalpha, through the downstream
      kinase Mnk1. TNFalpha production is inhibited in a concentration-dependent manner
      by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the
      inhibition targets posttranscriptional regulation and is paralleled by inhibition
      of the phosphorylation of eukaryotic initiation factor 4E (eIF4E). Unexpectedly,
      the activation/inhibition of MAPKAP kinase-2 (MK2) does not parallel TNFalpha
      production, arguing against a direct/immediate role for this kinase. On the basis
      of the present and previous results we propose that ARE-containing TNFalpha mRNA
      requires phosphorylation of eIF4E for initiation of translation.

PMID- 16431126
TI  - Effect of vanadyl sulfate on the status of lipid parameters and on stomach and
      spleen tissues of streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is a significant risk factor for cardiovascular complications.
      Experimental evidence suggests that oxidative stress plays a dominant role in the
      pathogenesis of diabetes mellitus. This study was undertaken to investigate the
      effect of vanadyl sulfate on blood glucose, serum and tissue lipid profiles and
      on stomach and spleen tissues in STZ-induced diabetic rats. In this study, male 6
      6.5-month-old Swiss albino rats were used. Rats were randomly divided into four
      groups. Group I: control animals (normal, nondiabetic animals) (n = 13); Group
      II: vanadyl sulfate controls (n = 5); Group III: streptozotocin (STZ)-diabetic,
      untreated animals (n = 11); and Group IV: STZ diabetic animals given vanadyl
      sulfate (n = 11). Experimental diabetes was induced by intraperitoneal (i.p.)
      injection of STZ in a single dose of 65 mg kg(-1) body weight. Vanadyl sulfate
      was administered by gavage at a dose of 100 mg kg(-1). The levels of cholesterol,
      phospholipid, high density lipoprotein-cholesterol (HDL-), low density
      lipoprotein-cholesterol (LDL-), very low density lipoprotein-cholesterol (VLDL-),
      triglycerides and lipid peroxidation (LPO) in serum and cholesterol in liver were
      assayed according to standard procedures. The levels of lipid peroxidation,
      glutathione (GSH) and nonenzymatic glycosylation (NEG) in stomach and lipid
      peroxidation and glutathione (GSH) in spleen tissues were analyzed. After 60 days
      of treatment, serum cholesterol, LDL-cholesterol, triglyceride, phospholipid,
      VLDL-cholesterol, LPO, blood glucose levels, stomach LPO and NEG, spleen LPO
      significantly increased, but serum HDL-cholesterol, stomach GSH and spleen GSH
      levels significantly decreased in the diabetic group. On the other hand,
      treatment with vanadyl sulfate reversed these effects. These results reveal that
      diabetes mellitus increased oxidative damage in stomach and spleen tissues and
      vanadyl sulfate has an ameliorating effect on the oxidative stress via its
      antioxidant property. The administration of vanadyl sulfate may be able to reduce
      hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.

PMID- 16431127
TI  - Role of transcription factors in commitment and differentiation of early B
      lymphoid cells.
AB  - B lymphopoiesis is a differentiation process in which hematopoietic stem cells
      are converted into antibody-producing plasma cells. B cell differentiation
      involves multiple steps, including cell specification, commitment to the B cell
      lineage, immunoglobulin rearrangements, maturation of B cells and terminal
      differentiation into plasma cells. Each of these steps is controlled by signaling
      pathways and transcription factors that act in synergy, feedback-loops or cross
      antagonism to generate complex regulatory networks that allow for plasticity and
      stability of B cell differentiation.

PMID- 16431128
TI  - CD4+CD25+ regulatory T cells in human hematopoietic cell transplantation.
AB  - Naturally occurring CD4+CD25+ regulatory T cells (T(reg)) are differentiated T
      lymphocytes actively involved in the control of peripheral immunity. Over the
      past few years, a number of animal studies have demonstrated the critical role of
      these cells in the outcome of allogeneic hematopoietic stem cell transplantation
      (HCT). In these models, T(reg) can exert a potent suppressive effect on immune
      effector cells reactive to host antigens and prevent graft versus host disease
      (GVHD) while preserving the graft-versus-leukemia effect (GVL). The present
      review summarizes current knowledge on the role of T(reg) populations in humans
      following allogeneic HCT. Recent investigations focusing on T(reg) in transplant
      patients have generated conflicting results mostly due to the use of different
      parameters to assess T(reg). Nonetheless, these studies suggested that an
      imbalance between T(reg) and effector cells during immune reconstitution can
      substantially impair regulatory mechanisms and contributes to the development of
      GVHD. Building on these studies, a number of therapeutic strategies are being
      developed to positively modulate T(reg) pools in vivo and prevent or even correct
      GVHD. Conversely, clinical interventions can also be envisaged to decrease T(reg)
      activity in vivo and enhance the GVL effect. These potential strategies are
      discussed herein. Coming years will undoubtedly yield additional knowledge on how
      to use T(reg) subsets in vivo and successfully control and modulate immune
      responses in patients post-HCT.

PMID- 16431129
TI  - PACAP support of neuronal survival requires MAPK- and activity-generated signals.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in the
      parasympathetic ciliary ganglion (CG) and modulates nicotinic acetylcholine
      receptor function. PACAP also provides trophic support, promoting partial
      survival of CG neurons in culture and full survival when accompanied by membrane
      depolarization. We probed the adenylate cyclase (AC) and phospholipase-C (PLC)
      transduction cascades stimulated by PACAP to determine their respective roles in
      supporting neuronal survival and examined their interaction with signals
      generated by membrane activity. While PLC-dependent signaling was dispensable, AC
      generated signals proved critical for PACAP to support neuronal survival.
      Specifically, PACAP-supported survival was mimicked by 8Br-cAMP and blocked by
      inhibiting either PKA or the phosphorylation of mitogen-activated protein kinase
      (MAPK). The ability of PACAP to promote survival was additionally dependent on
      spontaneous activity as blocking Na+ or Ca2+ channel currents completely
      abrogated trophic effects. Our results underscore the importance of coordinated
      MAPK- and activity-generated signals in transducing neuropeptide-mediated
      parasympathetic neuronal survival.

PMID- 16431130
TI  - Noninvasive telemetric gaze tracking in freely moving socially housed prosimian
      primates.
AB  - Behavioral and neurophysiological studies strongly suggest that visual orienting
      reflects the integration of sensory, motor, and motivational variables.
      Relatively little is known, however, regarding the goals that govern visual
      orienting of animals in their natural environments. Field observations suggest
      that most nonhuman primates orient to features of their natural environments
      whose salience is dictated by the visual demands of foraging, locomotion, and
      social interaction. This hypothesis is difficult to test quantitatively, however,
      in part because accurate gaze-tracking technology has not been employed in field
      studies. We here report the implementation of a new, telemetric, infrared-video
      gaze-tracker to measure visual orienting in freely moving, socially housed
      prosimian primates (Lemur catta). Two male lemurs tolerated the system at
      approximately 1/4 body weight, permitting successful measurements of gaze
      behavior during spontaneous locomotion through both terrestrial and arboreal
      landscapes, and in both social and asocial environments.

PMID- 16431131
TI  - Mucosal immunization using recombinant plant-based oral vaccines.
AB  - The induction of mucosal immunity is very important in conferring protection
      against pathogens that typically invade via mucosal surfaces. Delivery of a
      vaccine to a mucosal surface optimizes the induction of mucosal immunity. The
      apparent linked nature of the mucosal immune system allows delivery to any
      mucosal surface to potentially induce immunity at others. Oral administration is
      a very straightforward and inexpensive approach to deliver a vaccine to the
      mucosal lining of the gut. However, vaccines administered by this route are
      subject to proteolysis in the gastrointestinal tract. Thus, dose levels for
      protein subunit vaccines are likely to be very high and the antigen may need to
      be protected from proteolysis for oral delivery to be efficacious. Expression of
      candidate vaccine antigens in edible recombinant plant material offers an
      inexpensive means to deliver large doses of vaccines in encapsulated forms.
      Certain plant tissues can also stably store antigens for extensive periods of
      time at ambient temperatures, obviating the need for a cold-chain during vaccine
      storage and distribution, and so further limiting costs. Antigens can be
      expressed from transgenes stably incorporated into a host plant's nuclear or
      plastid genome, or from engineered plant viruses infected into plant tissues.
      Molecular approaches can serve to boost expression levels and target the
      expressed protein for appropriate post-translational modification. There is a
      wide range of options for processing plant tissues to allow for oral delivery of
      a palatable product. Alternatively, the expressed antigen can be enriched or
      purified prior to formulation in a tablet or capsule for oral delivery. Fusions
      to carrier molecules can stabilize the expressed antigen, aid in antigen
      enrichment or purification strategies, and facilitate delivery to effector sites
      in the gastrointestinal tract. Many antigens have been expressed in plants. In a
      few cases, vaccine candidates have entered into early phase clinical trials, and
      in the case of farmed animal vaccines into relevant animal trials.

PMID- 16431132
TI  - Frequency of attendance at religious services, overweight, and obesity in
      American women and men: the Third National Health and Nutrition Examination
      Survey.
AB  - PURPOSE: Few data have been published on the association of overweight and
      obesity and indices of religiousness, a putative protective factor for
      cardiovascular morbidity and mortality, in representative samples of multiethnic
      total populations. METHODS: To test the hypothesis that frequency of attendance
      at religious services is unrelated to the prevalence of overweight and obesity,
      the following data from American men and women aged 20 years and older (N =
      16,657) in a cross-sectional survey of a large national sample, the Third
      National Health and Nutrition Examination Survey, were analyzed: self-reported
      frequency of attendance at religious services, cigarette smoking, health status,
      sociodemographic variables, and measured body mass index (BMI). RESULTS: In
      persons 20 years and older, 58% of frequent attenders (> or = 52 times/y) and 53%
      of others were overweight or obese (BMI > or = 25 kg/m2). After stratifying to
      eliminate interactions in a logistic regression model and controlling for
      sociodemographics, smoking, and health status, no significant association was
      seen in European-American women overall. In all others, the significant positive
      associations of frequency of attendance and overweight could be explained by
      these other variables (fully adjusted odds ratio, 1.16; 95% confidence interval,
      0.98-1.36; p = 0.08). The same was true for obesity (BMI > or = 30 kg/m2).
      CONCLUSION: In a national sample of the US population, the prevalence of
      overweight or obesity is greater in self-reported frequent attenders of religious
      services than in others, but the association was explained by controlling for
      multiple sociodemographic and health variables.

PMID- 16431133
TI  - Biologic and social determinants of sequelae and long-term survival of pediatric
      HIV in Romania.
AB  - PURPOSE: The aim of the study is to investigate the effect of social context and
      clinical factors on survival in a cohort of 333 children to identify issues
      useful in the treatment and care of human immunodeficiency virus (HIV)-infected
      youth in developing countries. METHODS: A prospective cohort study design was
      used, and data were gathered at baseline and 1-year follow-up. The study cohort
      consisted of children given a diagnosis of HIV between 1995 and 1999 and
      receiving medical care in Constanta, Romania. Data were examined by means of
      multivariate Cox regression analysis models. RESULTS: The majority of the cohort
      were in the moderate (41%) or severe (40%) stages of HIV at baseline.
      Multivariate analysis indicated that social-context factors were the most
      significant determinants of HIV survival. The hazard for death for those with
      mothers or fathers with a higher level of education was approximately one quarter
      (relative hazard, 0.3-0.4; confidence interval, 0.1-1.0) that for a parent with a
      lower level of education. Subjects with employed mothers were four times more
      likely to survive than subjects with unemployed mothers. CONCLUSIONS: Results
      suggest that recognition of social-context risk factors for HIV disease
      progression and survival is important in developing countries, as it is in
      developed countries.

PMID- 16431134
TI  - Stillbirth risk factors according to timing of exposure.
AB  - PURPOSE: The purpose of the present study is to identify risk factors for
      stillbirth and explore hypotheses about the cause of stillbirth based on the time
      in gestation when exposures occur. METHODS: Relationships between lifestyle
      factors, pregnancy conditions, medication use, and occupation on risk for
      stillbirth were examined within a population-based case-control study. Women who
      had a stillbirth and a random sample of women who had a live birth between 1999
      and 2001 were identified through perinatal databases in Nova Scotia and Eastern
      Ontario, Canada. Exposure data were collected for each month of pregnancy and
      analyzed within trimesters. Case-control data were converted to case-cohort data,
      and hazard ratios (HRs) and 95% confidence intervals (CIs) were determined from
      Cox proportional hazards models. RESULTS: This study included 105 stillbirth
      cases and 389 live-birth controls. Fertility treatment in the present pregnancy
      was associated with increased risk for stillbirth (adjusted HR, 4.0; 95% CI, 1.4
      11.6). Smoking during the first trimester also was associated with increased risk
      for stillbirth (adjusted HR, 2.4; 95% CI, 1.2-4.9). Other risk factors included
      antiemetic use during the first trimester, second-trimester antibiotic use, low
      family income, and age older than 35 years. CONCLUSIONS: Risk factors identified
      in this study concur with findings of previous studies and support the importance
      of early pregnancy exposures on stillbirth risk.

PMID- 16431135
TI  - A potential inverse association between insulin-like growth factor I and
      hypertension in a cross-sectional study.
AB  - PURPOSE: Elevated circulating insulin-like growth factor I (IGF-I) levels
      increasingly are being implicated as a potential risk factor for the development
      of some cancers; however, relatively few epidemiologic studies have focused on
      potential relationships between circulating IGF-I levels and cardiovascular risk
      factors or cardiovascular disease. Hence, our objective is to examine
      relationships between IGF-I levels; body mass index (BMI); fasting insulin level;
      IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 levels; and an array of
      traditional cardiovascular risk factors. METHODS: Our analysis included 715 men
      and women aged 30 to 62 years who participated in the Vasterbotten Intervention
      Project cohort. IGF-I and IGFBP-1, -2, and -3 were measured in stored plasma
      samples. Cardiovascular risk factors of interest included glucose level (fasting
      and 2-hour postload), lipid levels (total cholesterol, high-density lipoprotein
      cholesterol, and triglycerides), blood pressure (systolic and diastolic), and
      hypertension status. All presented results were adjusted for age, sex, and
      laboratory batch. RESULTS: IGF-I quartile was associated inversely with 2-hour
      glucose level and diastolic blood pressure. There was a stepwise inverse graded
      association between increasing IGF-I quartile and hypertension, with an odds
      ratio of 0.51 (95% confidence interval, 0.29-0.90) for hypertension comparing the
      fourth IGF-I quartile with the first. Further adjusting for BMI and IGFBP-3 level
      simultaneously strengthened the inverse association, with an odds ratio of 0.42
      (95% confidence interval, 0.22-0.80) for hypertension comparing the fourth with
      the first IGF-I quartile. CONCLUSIONS: Contrary to positive associations between
      IGF-I levels and some cancers, our results suggest that IGF-I level may be
      related inversely to prevalent hypertension, a risk factor for cardiovascular
      disease.

PMID- 16431136
TI  - The orthogonal tilt reconstruction method: an approach to generating single-class
      volumes with no missing cone for ab initio reconstruction of asymmetric
      particles.
AB  - Generating reliable initial models is a critical step in the reconstruction of
      asymmetric single-particles by 3D electron microscopy. This is particularly
      difficult to do if heterogeneity is present in the sample. The Random Conical
      Tilt (RCT) method, arguably the most robust presently to accomplish this task,
      requires significant user intervention to solve the "missing cone" problem. We
      present here a novel approach, termed the orthogonal tilt reconstruction method,
      that eliminates the missing cone altogether, making it possible for single-class
      volumes to be used directly as initial references in refinement without further
      processing. The method involves collecting data at +45 degrees and -45 degrees
      tilts and only requires that particles adopt a relatively large number of
      orientations on the grid. One tilted data set is used for alignment and
      classification and the other set--which provides views orthogonal to those in the
      first--is used for reconstruction, resulting in the absence of a missing cone. We
      have tested this method with synthetic data and compared its performance to that
      of the RCT method. We also propose a way of increasing the level of homogeneity
      in individual 2D classes (and volumes) in a heterogeneous data set and
      identifying the most homogeneous volumes.

PMID- 16431137
TI  - Variable precision registration via wavelets: optimal spatial scales for inter
      subject registration of functional MRI.
AB  - The detection of significantly activated brain regions in multi-subject
      functional magnetic resonance imaging (fMRI) studies almost invariably entails
      the coregistration of individual subjects' data in a standard space. Here, we
      investigate how sensitivity to detect loci of generic activation in such studies
      may be conditioned by the precision of anatomical registration. We describe a
      novel algorithm, implemented in the wavelet domain, for inhomogeneous deformation
      of individual images to match a template. The algorithm matches anatomical
      features in a coarse-to-fine fashion, first minimising a cost function in terms
      of relatively coarse spatial features and then proceeding iteratively to match
      the images in terms of progressively more detailed anatomical features. Applying
      the method to data acquired from two groups of 12 healthy volunteers (with mean
      age 27 and 70 years, respectively), during performance of a paired associate
      learning task, we show that geometrical overlap between template and individual
      images is monotonically improved, compared to an affine transform, by additional
      inhomogeneous deformations informed by more detailed features. Likewise,
      sensitivity to detect activated voxels can be substantially improved, by a factor
      of 4 or more, if wavelet-mediated deformations informed by medium-sized
      anatomical features are applied in addition to a preliminary affine transform.
      However, sensitivity to detect activated voxels was reduced by "over-registering"
      data or matching anatomical features at the finest scales of the wavelet
      transform. The benefits of variable precision registration are particularly
      salient for data acquired in older subjects, which showed evidence of greater
      inter-subject anatomic variability and generally required more extensive local
      deformation to achieve a satisfactory match to the template image. We conclude
      that major benefits in sensitivity to detect functional activation in multi
      subject fMRI studies can be attained with an inhomogeneous deformation applied
      over appropriate spatial scales.

PMID- 16431138
TI  - TE-averaged two-dimensional proton spectroscopic imaging of glutamate at 3 T.
AB  - Glutamate and glutamine are important neurochemicals in the central nervous
      system and the neurotoxic properties of excess glutamate have been associated
      with several neurodegenerative diseases. The TE-Averaged PRESS technique has been
      shown by our group to detect an unobstructed glutamate signal at 3 T that is
      resolved from glutamine and NAA at 2.35 ppm. TE-Averaged PRESS therefore provides
      an unambiguous measurement of glutamate as well as other metabolites such as NAA,
      choline, creatine, and myo-inositol. In this study, we extend the single voxel TE
      Averaged PRESS technique for two-dimensional (2D) spectroscopic imaging (TE
      Averaged MRSI) to generate 2D glutamate maps. To facilitate TE-Averaged MRSI
      within a reasonable time, a fast encoding trajectory was used. This enabled rapid
      acquisition of TE-Averaged spectral arrays with good spectral bandwidth (977 Hz)
      and resolution (approximately 2 Hz). MRSI data arrays of 10 x 16 were acquired
      with 1.8 cm3 spatial resolution over a approximately 110 cm3 volume in a scan
      time of approximately 21 min. Two-dimensional metabolite maps were obtained with
      good SNR and clear differentiation in glutamate levels was observed between gray
      and white matter with significantly higher glutamate in gray matter relative to
      white matter as anticipated.

PMID- 16431139
TI  - Collateral nerve fibers in human spinal cord: visualization with magnetic
      resonance diffusion tensor imaging.
AB  - Diffusion tensor magnetic resonance imaging provides structural information about
      nerve fiber tissue. The first eigenvector of the diffusion tensor is aligned with
      the nerve fibers, i.e., longitudinally in the spinal cord. The underlying
      hypothesis of this study is that the presence of collateral nerve fibers running
      orthogonal to the longitudinal fibers results in an orderly arrangement of the
      second eigenvectors. Magnetic resonance diffusion tensor scans were performed
      with line scan diffusion imaging on a clinical MR scanner. Axial sections were
      scanned in a human cervical spinal cord specimen at 625 microm resolution and the
      cervical spinal cord of four normal volunteers at 1250 microm resolution. The
      spinal cord specimen was fixed and stained for later light microscopy of the
      collateral fiber architecture at 0.53 microm resolution. Diffusion measured by MR
      was found to be anisotropic for both white and gray matter areas of the spinal
      cord specimen; the average fractional anisotropy (FA) was 0.63 +/- 0.09
      (diffusion eigenvalues lambda1 0.38 +/- 0.05 micros/mm2, lambda2 0.14 +/- 0.03
      micros/mm2, lambda3 0.10 +/- 0.03 micros/mm2) in white matter and 0.27 +/- 0.04
      (lambda1 0.36 +/- 0.04 micros/mm2, lambda2 0.28 +/- 0.03 micros/mm2, lambda3 0.21
      +/- 0.04 micros/mm2 in gray matter. The normal-volunteer FA values were similar,
      i.e., 0.66 +/- 0.04 (lambda1 1.66 +/- 0.14 micros/mm2, lambda2 0.55 +/- 0.02
      micros/mm2, lambda3 0.40 +/- 0.01 micros/mm2) in white matter and 0.35 +/- 0.03
      (lambda1 1.14 +/- 0.07 micros/mm2, lambda2 0.70 +/- 0.03 micros/mm2, lambda3 0.58
      +/- 0.02 micros/mm2) in gray matter. The first eigenvector pointed, as expected,
      in the longitudinal direction. The second eigenvector directions exhibited a
      striking arrangement, consistent with the distribution of interconnecting
      collateral nerve fibers discerned on the histology section. This finding was
      confirmed for the specimen by quantitative pixel-wise comparison of second
      eigenvector directions and collateral fiber directions assessed on light
      microscopy image data. Diffusion tensor MRI can reveal non-invasively and in
      great detail the intricate fiber architecture of the human spinal cord.

PMID- 16431140
TI  - Premature osteoarthritis in the Disproportionate micromelia (Dmm) mouse.
AB  - OBJECTIVE: Degeneration of articular cartilage leads to the development of
      osteoarthritis (OA), but the molecular pathology of the disease is poorly
      understood. The Disproportionate micromelia (Dmm) mouse has a deletion mutation
      in the C-propeptide encoding region of Col2a1, which leads to a defective
      cartilage matrix. The objective of this study was to determine whether
      heterozygous (Dmm/+) mice develop premature OA, and could therefore serve as an
      animal model for studying the molecular pathways leading to OA. DESIGN:
      Histological analysis was utilized to determine the state of articular cartilage
      degeneration in Dmm/+ mice at 3, 6, 9, 12, 15, and 22 months of age. Severity of
      OA was quantified with a modified Mankin scoring system. In addition, articular
      cartilage thickness, cell density, and the extracellular matrix (ECM) fraction of
      articular cartilage were quantified. RESULTS: Articular cartilage erosion was
      significantly more severe in Dmm/+ than in wild-type (+/+) mice beginning at 9
      months, and modified Mankin scoring revealed Dmm/+ articular cartilage to be in a
      more severe osteoarthritic state as early as 3 months. In addition, Dmm/+
      articular cartilage was thinner than +/+ cartilage and showed increased cell
      density and decreased matrix fraction compared with +/+ from the earliest time
      points measured. CONCLUSIONS: The present study demonstrates that Dmm/+ mice
      develop premature OA. The observed degenerative changes of Dmm/+ articular
      cartilage closely resemble those of human OA patients, with or without Col2a1
      mutations, suggesting that Dmm/+ mice are a useful model for investigating
      mechanisms involved in OA.

PMID- 16431141
TI  - Hyaluronate effects on synovium and synovial fluid. A prospective blinded study
      in patients with osteoarthritis of the knee.

PMID- 16431142
TI  - Current trends in the diagnosis and management of renal nutcracker syndrome: a
      review.
AB  - Nutcracker syndrome is caused by compression of the left renal vein between the
      aorta and the superior mesenteric artery where it passes in the fork formed at
      the bifurcation of these arteries. The phenomenon results in left renal venous
      hypertension. The syndrome is manifested by left flank and abdominal pain, with
      or without unilateral haematuria. Other common presentation is as "pelvic
      congestion syndrome" characterized by symptoms of dysmenorrhea, dyspareunia, post
      coital ache, lower abdominal pain, dysuria, pelvic, vulvar, gluteal or thigh
      varices and emotional disturbances. Likewise compression of the left renal vein
      can cause left renal-to-gonadal vein reflux resulting in lower limb varices and
      varicoceles in males. Its diagnosis is based on history and physical examination,
      basic lab tests to exclude other causes of haematuria, cystoscopy and
      ureteroscopy to confirm unilateral haematuria and exclude other causes of this
      sinister symptom. Sequence of imaging has more or less been rationalised to USS
      with Doppler studies, CT or MR angiography and finally phlebography with renal
      vein and IVC manometery to confirm the diagnosis.

PMID- 16431144
TI  - Structure and adsorption of a basic probe molecule on H-ZSM-5 nanostructured
      zeolite: an embedded ONIOM study.
AB  - The adsorption properties of pyridine on H-ZSM-5 zeolites have been investigated
      by cluster calculations with the ONIOM scheme and with an embedded-ONIOM scheme.
      The active site has been modeled with cluster sizes of up to 46 tetrahedra. Two
      different types of pyridine adsorption complexes on the zeolite models are found.
      If Zeolite is modeled by a small 3T quantum cluster, the adsorption energy of the
      hydrogen-bonded pyridine complex (Py-Hz), is found to be -18.5kcal/mol. When a
      larger cluster or the ONIOM models are employed, the optimized geometries show
      the formation of pyrdinium cation [PyH(+)] bound as an ion-pair complex
      [PyH(+)][Z(-)]. The calculated energy of formation for this ion-pair complex is 
      36.8kcal/mol in the ONIOM (B3LYP/6-31G(d,p):UFF) model. Both values are
      considerably lower than the experimentally estimated heat of adsorption of
      pyridine in ZSM-5 zeolite of -47.6kcal/mol. Inclusion of the electrostatic
      effects of the zeolite crystal lattice via the embedded ONIOM model increases the
      adsorption energy to -44.4kcal/mol. Performing the quantum-chemical treatment at
      the MP2/6-31G(d,p) level instead of the B3LYP/6-31G(d,p) leads to a slightly
      lower adsorption energy to -45.9kcal/mol. These data suggest that the embedded
      ONIOM scheme provides an accurate method of studying the interaction of small
      organic molecules with zeolites.

PMID- 16431143
TI  - Insight into the CSA tensors of nucleobase carbons in RNA polynucleotides from
      solution measurements of residual CSA: towards new long-range orientational
      constraints.
AB  - Using residual chemical shift anisotropies (RCSAs) measured in a weakly aligned
      stem-loop RNA, we examined the carbon chemical shift anisotropy (CSA) tensors of
      nucleobase adenine C2, pyrimidine C5 and C6, and purine C8. The differences
      between the measured RCSAs and the values back-calculated using three nucleobase
      carbon CSA sets [D. Stueber, D.M. Grant, 13C and 15N chemical shift tensors in
      adenosine, guanosine dihydrate, 2'-deoxythymidine, and cytidine, J. Am. Chem.
      Soc. 124 (2002) 10539-10551; D. Sitkoff, D.A. Case, Theories of chemical shift
      anisotropies in proteins and nucleic acids, Prog. NMR Spectrosc. 32 (1998) 165
      190; R. Fiala, J. Czernek, V. Sklenar, Transverse relaxation optimized triple
      resonance NMR experiments for nucleic acids, J. Biomol. NMR 16 (2000) 291-302]
      reported previously for mononucleotides (1.4 Hz) is significantly smaller than
      the predicted RCSA range (-10-10 Hz) but remains larger than the RCSA measurement
      uncertainty (0.8 Hz). Fitting of the traceless principal CSA values to the
      measured RCSAs using a grid search procedure yields a cytosine C5 CSA magnitude
      (CSAa=(3/2.(delta11(2)+delta22(2)+delta33(2)))1/2=173+/-21 ppm), which is
      significantly higher than the reported mononucleotide values (131-138 ppm) and a
      guanine C8 CSAa (148+/-13 ppm) that is in very good agreement with the
      mononucleotide value reported by solid-state NMR [134 ppm, D. Stueber, D.M.
      Grant, 13C and (15)N chemical shift tensors in adenosine, guanosine dihydrate, 2'
      deoxythymidine, and cytidine, J. Am. Chem. Soc. 124 (2002) 10539-10551]. Owing to
      a unique sensitivity to directions normal to the base plane, the RCSAs can be
      translated into useful long-range orientational constraints for RNA structure
      determination even after allowing for substantial uncertainty in the nucleobase
      carbon CSA tensors.

PMID- 16431145
TI  - The effects of pH and the iron redox state on iron uptake in the intestine of a
      marine teleost fish, gulf toadfish (Opsanus beta).
AB  - In the marine teleost intestine the secretion of bicarbonate increases pH of the
      lumen (pH 8.4 -9.0) and importantly reduces Ca2+ and Mg2+ concentrations by the
      formation of insoluble divalent ion carbonates. The alkaline intestinal
      environment could potentially also cause essential metal carbonate formation
      reducing bioavailability. Iron accumulation was assessed in the Gulf toadfish
      (Opsanus beta) gut by mounting intestine segments in modified Ussing chambers
      fitted to a pH-stat titration system. This system titrates to maintain lumen pH
      constant and in the process prevents bicarbonate accumulation. The luminal saline
      pH was clamped to pH 5.5 or 7.0 to investigate the effect of proton
      concentrations on iron uptake. In addition, redox state was altered (gassing with
      N2, addition of dithiothreitol (DTT) and ascorbate) to evaluate Fe3+ versus Fe2+
      uptake, enabling us to compare a marine teleost intestine model for iron uptake
      to the mammalian system for non-haem bound iron uptake that occurs via a
      ferrous/proton (Fe2+/H+) symporter called Divalent Metal Transporter 1 (DMT1).
      None of the redox altering strategies affected iron (Fe3+ or Fe2+) binding to
      mucus, but the addition of ascorbate resulted in a 4.6-fold increase in
      epithelium iron accumulation. This indicates that mucus iron binding is
      irrespective of valency and suggests that ferrous iron is preferentially
      transported across the apical surface. Altering luminal saline pH from 7.0 to 5.5
      did not affect ferric or ferrous iron uptake, suggesting that if iron is entering
      via DMT1 in marine fish intestine this transporter works efficiently under
      circumneutral conditions.

PMID- 16431146
TI  - Myocardial contractility in chickens (Gallus gallus): analysis of systolic time
      intervals.
AB  - The avian cardiovascular system is of special interest because avian hearts are
      relatively larger than mammalian hearts, and activation of ventricular myocardium
      in birds has a "flash" pattern. Systolic time intervals and indices of myocardial
      contractility were examined in anaesthetized open-chest chickens by
      polycardiography, including synchronous recordings of electrocardiogram,
      phonocardiogram, and apex cardiogram. The asynchronous contraction time,
      isometric contraction time, pre-ejection period and ejection time were 26 +/- 3
      (Mean +/- SD), 21 +/- 9, 47 +/- 12, and 83 +/- 23 ms, respectively, for heart
      rates of 260 +/- 57 bpm. The myocardial tension index, isometric contraction
      index and the pre-ejection period/ejection time ratio were 0.39 +/- 0.11, 0.42 +/
      0.10, and 0.54 +/- 0.14, respectively. A "flash" pattern of ventricular
      myocardial depolarization causes more rapid excitation and as a consequence
      shorter asynchronous contraction time of relatively larger chicken hearts
      compared with rabbit hearts. Inverse relation (P < 0.05) of the asynchronous
      contraction time to the heart rate in chickens is probably associated with the
      specific activation pattern of avian ventricles. Establishment of the values of
      systolic time intervals will facilitate a better understanding of cardiac
      function in birds. The obtained results are discussed in comparison with the
      rabbit. The indices calculated from the systolic time intervals show
      disadvantageous contractile function of chicken heart compared to rabbit heart.

PMID- 16431147
TI  - Serum IGF-I levels are similar in Samoan, Maori and European populations despite
      differences in body composition.
AB  - OBJECTIVE: To determine if serum IGF-I concentrations are similar in healthy
      adult subjects from the Samoan, Maori and European populations in New Zealand.
      DESIGN: Serum IGF-I concentration was measured in 75 healthy adults, aged 18-50
      years, of Samoan (n=23), Maori (n=22) and European (n=30) descent. Body
      composition was assessed using standard anthropomorphic measures. In addition all
      subjects had body composition assessed by Dual energy X-ray absorptiometry (DXA).
      RESULTS: Weight, body mass index (BMI), and fat mass were significantly greater
      in Maori and Samoan subjects than European subjects (ANOVA p=0.006, p=0.0003,
      p=0.03, respectively). However, serum IGF-I concentration was similar between the
      groups (European 186.8 SEM 14.9 microg/l, Maori 204.8 SEM 17.1 microg/l, Samoan
      180.0 SEM 17.5 microg/l, p=0.58). IGF-I levels were similar between ethnic groups
      after adjustment (ANCOVA) for age, sex or BMI (p=0.5) or age, sex and fat mass
      (p=0.44). In multivariate analysis the only independent predictor of IGF-I was
      age (p<0.001) and explained 22% of the variance in IGF-I level. CONCLUSIONS:
      Serum IGF-I concentrations were similar in Maori, Samoan and European population
      groups in New Zealand, despite significant differences in anthropomorphic
      variables and body composition.

PMID- 16431148
TI  - Typhoid fever in children: some epidemiological considerations from Karachi,
      Pakistan.
AB  - BACKGROUND: The morbidity of typhoid fever is highest in Asia with 93% of global
      episodes occurring in this region. Southeast Asia has an estimated incidence of
      110 cases/100,000 population, which is the third highest incidence rate for any
      region. Pakistan falls into this region. There is also a considerable seasonal
      variation of typhoid fever, carrying significant public health importance.
      Children are worst affected. Population-based data from Pakistan are scarce.
      METHODS: From June 1999 to December 2001 a fortnightly surveillance system was
      established in two squatter settlements in Karachi, Pakistan, with two study
      centers, each staffed by a doctor and five community health workers. Cases of
      continuous high-grade fever for three or more days were referred to these centers
      and screened clinically. Blood culture and Typhidot tests were done. RESULTS: One
      third of the 4198 cases with febrile episodes of three or more days detected in
      the community were screened at the centers; 341 were clinically suspected of
      having typhoid fever. Forty-nine were positive by culture whereas 161 were
      positive by serology. Ten cases were multi-drug resistant. Incidence of culture
      proven typhoid was estimated to be 170 (95% CI: 120, 220)/100,000 population,
      whereas serology-based incidence was 710 (95% CI: 620, 810)/100,000 population.
      Peak incidence was noted in October followed by May and June. CONCLUSION: Passive
      surveillance, even when augmented by household visits, misses a significant
      portion of suspected cases. Morbidity of typhoid is quite high in Pakistan and
      needs public health intervention. Hot months have higher incidence of typhoid.
      Healthcare behavior studies will help to develop a better surveillance system.

PMID- 16431149
TI  - A facile way for preparing tin nanoparticles from bulk tin via ultrasound
      dispersion.
AB  - In this paper, we reported a facile and rapid process to prepare tin
      nanoparticles from bulk tin via ultrasound dispersion. The morphology and
      structure of synthesized tin nanoparticles were characterized by transmission
      electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectrum
      (XPS) and thermogravimetric analysis (TGA). The results show that the morphology
      of tin nanoparticles is spherical and the structure of tin nanoparticles has the
      same crystal structure as the bulk tin. In addition, the tribological property of
      tin nanoparticles as additives in oil is evaluated on a four-ball tester and the
      results show that tin nanoparticles exhibit good performance in wear.

PMID- 16431151
TI  - A new function of a previously isolated compound that stimulates activation and
      differentiation of myogenic precursor cells leading to efficient myofiber
      regeneration and muscle repair.
AB  - Muscle repair following severe injury is slow and incomplete due to the limited
      regenerative capacity of muscles comprising the function. In this study, one pure
      compound structurally corresponding to triterpenoid, which can directly induce
      the activation, proliferation and maturation of quiescent satellite cells into
      myocytes in vitro, was isolated from Geum japonicum. The potential effect of this
      compound on myogenesis was further tested in repair of severe muscle injury. It
      was found that this compound could significantly stimulate the regenerative
      potential of the damaged muscle resulting in regeneration of myotubes and myotube
      bundles time-dependently replacing the damaged muscle tissues. This compound
      mediated active regeneration of new myofibers repairing damaged muscles was
      probably due to its direct action on activation and proliferation of quiescent
      myogenic precursor cells and enhancement of their maturation into regenerating
      myotubes, as was demonstrated in our primary myogenic precursor cells culture
      experiments. The up-regulated expression of endogenous phospho-Akt1 in compound
      treated myogenic precursor cells may also contribute to the process of myofiber
      regeneration and muscle repair probably via promoting myogenic cell survival
      capacity.

PMID- 16431150
TI  - Isolation and in vitro characterization of pancreatic progenitor cells from the
      islets of diabetic monkey models.
AB  - Recent studies on the identification of stem/progenitor cells within adult mouse
      and human pancreatic islets have raised the possibility that autologous
      transplantation might be used in treating type 1 diabetes. However, it is not yet
      known whether such stem/progenitor cells are impaired in type 1 diabetic patients
      or diabetic animal models. The latter would also allow us to test the efficacy of
      autologous transplantation in large animal models prior to clinical applications.
      The present study aims to determine the existence of stem/progenitor cells in the
      islets of diabetic monkey models and to assess the proliferation and
      differentiation potential of such cells in vitro. Our results indicate that there
      are pancreatic progenitor cells in the adult pancreatic islets in both normal and
      type 1 diabetic monkeys. The isolated pancreatic progenitor cells can be greatly
      expanded in culture. Upon the removal of growth medium, these cells spontaneously
      form islet-like cell clusters, which could be further induced to secrete insulin
      by inductive factors. Furthermore, the secretion of insulin and C-peptide from
      the islet-like cell clusters responds to glucose and other stimuli, indicating
      that the differentiated cells not only resemble beta-cells but also possess the
      unique biological function of beta-cells. This study provides a foundation for
      further characterization of adult pancreatic progenitor cells and autologous
      transplantation using pancreatic progenitor cells in treating diabetic monkeys.

PMID- 16431152
TI  - Evaluation of genotoxicity in a group of workers from a petroleum refinery
      aromatics plant.
AB  - Petroleum refinery workers are potentially exposed to a wide range of petroleum
      derived hydrocarbons and chemical substances used in the manufacturing of
      petroleum derivatives. Benzene, toluene and xylene (BTX) are produced by
      distillation in the aromatics units and used as raw materials for petrol and
      petrochemical products. The aim of this study was to evaluate the genotoxic
      effects of occupational exposure to BTX in a petroleum refinery in the North of
      Portugal. The exposed group consisted of 48 workers from the aromatics plant and
      the control group consisted of 30 persons matched for various confounding
      factors. Chromosome aberrations (CA), micronuclei (MN), and DNA damage (evaluated
      by means of the comet assay) were measured in peripheral blood leukocytes. t,t
      Muconic acid (t,t-MA), hippuric acid (HA) and methylhippuric acid (MHA)
      concentrations were measured in urine samples collected at the end of the
      workshift. The results suggest that occupational exposure to toluene and xylene
      is very low. A statistically significant increase in t,t-MA excretion was found
      in the exposed group although t,t-MA levels were found to be lower than the
      biological exposure index (BEI). Significant increases were found for CA, MN and
      comet tail length (TL) in the exposed group (p<0.05). No association was found
      between tobacco smoking and the effect biomarkers analysed. A positive
      association was found between CA and MN with age in the control group (p<0.05).

PMID- 16431153
TI  - Spectrophotometric determination of flucloxacillin and dicloxacillin in pure and
      dosage forms.
AB  - A simple, rapid and accurate spectrophotometric method for the determination of
      antibiotic drugs, flucloxacillin (Fluclox) and dicloxacillin (Diclox), in pure
      form and different pharmaceutical preparations has been developed. The charge
      transfer (CT) reactions between Fluclox and Diclox as electron donors and 7,7,8,8
      tetracyanoquinodimethane (TCNQ) and tetracyanoethylene (TCNE) as pi-acceptors to
      give highly coloured complex species have been spectrophotometrically studied.
      The optimum experimental conditions for these CT reactions have been studied
      carefully. Beer's law is obeyed over the concentration ranges of 4-180 microg mL(
      1) and 4-70 microg mL(-1) for Fluclox and Diclox drugs using TCNQ and TCNE
      reagents, respectively. The Sandell sensitivities (S) are found to be 0.016-0.035
      microg cm(-2) and 0.011-0.016 microg cm(-2) for Fluclox and Diclox, respectively,
      which indicate the high sensitivity of the proposed method. The relative standard
      deviations (R.S.D.: 0.08-0.49 and 0.15-0.80) for the determination of Fluclox and
      (R.S.D.: 0.05-0.75 and 0.13-0.75) for Diclox were obtained for four to six
      replicates using TCNQ and TCNE reagents, respectively, refer to the high accuracy
      and precision of the proposed method. These results are also confirmed by the
      between-day precision and the percent recovery of 99.90-100.1 and 99.60-100.4 for
      Fluclox and 99.90-100.5 and 99.40-100.1 for Diclox using TNCQ and TCNE reagents,
      respectively. The results obtained for the two reagents are comparable with those
      obtained by the official method.

PMID- 16431154
TI  - Ultrasensitive quantitative HIV-1 p24 antigen assay adapted to dried plasma spots
      to improve treatment monitoring in low-resource settings.
AB  - BACKGROUND: Our group has previously developed a quantitative and ultrasensitive
      HIV-1 p24 antigen assay that is inexpensive, easy-to-perform, and can be carried
      out in low-resource settings. Since antiretroviral therapies are becoming more
      accessible in resource-constrained countries, methods to assess HIV-1 viraemia
      are urgently needed to achieve a high standard of care in HIV-1 management.
      OBJECTIVES: To adapt our quantitative assay to dried plasma spots (DPS), in order
      to further simplify this test and make it more accessible to resource-constrained
      countries. STUDY DESIGN: DPS from 47 HIV-seropositive, treated or untreated adult
      individuals and 30 healthy individuals were examined. RESULTS: A specificity of
      100% was observed when p24 antigen was measured using DPS, and no differences of
      p24 concentration could be seen between DPS and venous plasma. The correlation
      between DPS and venous plasma p24 was excellent (R=0.93, CI(95%)=0.88-0.96,
      p<0.0001). Similarly, p24 antigen concentrations using DPS were well correlated
      with RNA viral load (R=0.53, CI(95%)=0.27-0.72, p=0.0002). CONCLUSIONS: This
      quantitative p24 antigen test has similar sensitivity and specificity using DPS
      and venous plasma, and has the potential to improve health care delivery to HIV
      affected individuals in resource-constrained countries.

PMID- 16431155
TI  - Sphingolipid biosynthesis in pathogenic fungi: identification and
      characterization of the 3-ketosphinganine reductase activity of Candida albicans
      and Aspergillus fumigatus.
AB  - An early step in sphingolipid biosynthesis, the reduction of 3-ketosphinganine,
      is catalyzed in the yeast Saccharomyces cerevisiae by Tsc10p (TSC10 (YBR265W)).
      We have identified orthologs of TSC10 in two clinically important fungal
      pathogens, Candida albicans and Aspergillus fumigatus. The translated sequences
      of the putative C. albicans ortholog, KSR1 (orf6.5112), and the putative A.
      fumigatus ortholog, ksrA, show significant homology to the yeast protein. All
      three proteins contain the signature motifs of NAD(P)H-dependent oxidoreductases
      in the short-chain dehydrogenase/reductase family and a conserved putative
      substrate-binding domain. Despite being essential in S. cerevisiae, we
      demonstrate that the C. albicans ortholog, KSR1, is not required for cell
      viability. However, ksr1 null mutants produce lower levels of
      inositolphosphorylceramides, are significantly more sensitive than the wildtype
      to an inhibitor of a subsequent step in sphingolipid biosynthesis, and are
      defective for the transition from yeast to filamentous growth, a key virulence
      determinant. Recombinant, purified Ksr1p and KsrA can carry out the reduction of
      3-ketosphinganine in an NADPH-dependent manner. Molecular modeling of Ksr1p with
      bound substrates suggests that a significant portion of the aliphatic chain of 3
      ketosphinganine protrudes from the enzyme. Guided by this molecular model, we
      developed shorter, water-soluble derivatives of 3-ketosphinganine that are
      substrates for 3-ketosphinganine reductase.

PMID- 16431156
TI  - Phosphorylation regulates mitochondrial glycerol-3-phosphate-1 acyltransferase
      activity in T-lymphocytes.
AB  - Recently, we have shown that stimulation and recombinant ACBP increase
      mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT) activity in rat
      splenic T-lymphocytes and that this effect is blunted in aged T-lymphocytes. In
      addition to decreased mtGPAT activity, aged T-lymphocytes also have altered
      membrane lipid composition and decreased proliferation in response to antigen.
      Therefore, we wanted to determine the mechanism by which mtGPAT activity is
      regulated in aged T-lymphocytes. We show that aged T-lymphocyte mtGPAT activity
      is not increased by ex vivo stimulation or in vitro phosphorylation with casein
      kinase II and protein kinase C theta as is seen in young T-lymphocytes. However,
      other factors that might impact mtGPAT activity such as reduced mtGPAT protein
      levels, gene expression or alterations in the soluble acyl-CoA pool were not
      affected by age or stimulation. The age effect was also not compensated for by
      increased acyl-CoA binding protein expression in aged T-lymphocytes. Currently,
      two mitochondrial GPAT (mtGPAT) isoforms (mtGPAT1 and mtGPAT2) have been
      identified. We found that T-lymphocytes express mtGPAT1, but not mtGPAT2,
      suggesting that at least mtGPAT1 is sensitive to phosphorylation in vitro.
      Support for direct phosphorylation of mtGPAT1 in young T-lymphocytes is shown by
      mtGPAT1 immunoprecipitation where a phosphoprotein band was detected migrating at
      the same molecular weight (85 kDa) as mtGPAT1. This is significant because we
      also show that T-lymphocytes from mtGPAT1 KO mice have reduced proliferation ex
      vivo as is seen in aged T-lymphocytes. These data provide evidence for a novel
      mechanism by which T-lymphocyte proliferation may be regulated and, for the first
      time, give a potential mechanistic explanation for the correlation between
      reduced proliferation and membrane lipid changes seen in aged T-lymphocytes.

PMID- 16431157
TI  - A multiple PCR-primer approach to access the microeukaryotic diversity in
      environmental samples.
AB  - The Cariaco Basin off the Venezuelan coast in the Caribbean Sea is the world's
      largest truly marine body of anoxic water. The first rRNA survey of microbial
      eukaryotes in this environment revealed a number of novel lineages, but sampled
      only a fraction of the entire diversity. The goal of this study was to
      significantly improve recovery of protistan rRNA from the Basin. This was
      achieved by a systematic application of multiple PCR primer sets and
      substantially larger sequencing efforts. We focused on the most diverse habitat
      in the basin, anoxic waters approximately 100m below the oxic-anoxic interface,
      and detected novel lineages that escaped the single PCR primer approach. All
      clones obtained proved unique. A 99% sequence similarity cut-off value combined
      these clones into operational taxonomic units (OTUs), over 75% of which proved
      novel. Some of these OTUs form deep branches within established protistan groups.
      Others signify discovery of novel protistan lineages that appear unrelated to any
      known microeukaryote. Surprisingly, even this large-scale multi-primer rRNA
      approach still missed a substantial part of the samples' rRNA diversity. The
      overlap between the species lists obtained with different primers is low, with
      only 4% of OTUs shared by all three libraries, and the number of species detected
      only once is large (55%). This strongly indicates that, at least in anoxic
      environments, protistan diversity may be much larger than is commonly thought. A
      single sample appears to contain thousands of largely novel protistan species.
      Multiple PCR primer combinations may be needed to capture these species.

PMID- 16431158
TI  - DNA barcoding of blastocystis.
AB  - We have developed a simple method for subtyping the intestinal protistan parasite
      Blastocystis using an approach equivalent to DNA barcoding in animals.
      Amplification of a 600 bp region of the small subunit ribosomal RNA gene followed
      by single primer sequencing of the PCR product provides enough data to assign
      isolates to specific subtypes unambiguously. We believe that this approach will
      prove useful in future epidemiological studies.

PMID- 16431159
TI  - Present status of the molecular ecology of kathablepharids.

PMID- 16431161
TI  - Abnormal pulmonary vascular responses in patients registered with a systemic
      autoimmunity database: Pulmonary Hypertension Assessment and Screening Evaluation
      using stress echocardiography (PHASE-I).
AB  - Patients with autoimmune disease, and in particular limited systemic sclerosis
      (CREST syndrome), are at risk of developing pulmonary artery hypertension (PAH)
      which is associated with a poor prognosis. With improvements in therapy offering
      improved survival and functional capacity, there has been an emphasis on
      screening to identify patients at risk. Assessment of patients during exercise
      may enable early identification of patients with this condition. AIMS AND
      METHODS: We aimed to assess the ability of exercise stress echocardiography to
      evaluate the change in pulmonary artery pressure in 51 patients with autoimmune
      disease (systemic lupus erythamatosus (SLE), limited systemic sclerosis (LSS or
      "CREST") and diffuse systemic sclerosis (DSS)). Systolic pulmonary artery
      pressure (sPAP) was estimated using interrogation of the tricuspid incompetence
      jet before and after exercise. PAH was classified as normal, mild, moderate or
      severe using echocardiographic assessment of sPAP. RESULTS: We were able to
      estimate pre-exercise and post-exercise sPAP in 92% and 90% of patients,
      respectively. Pulmonary pressures rose or remained unchanged in all screened
      individuals, with a mean rise during stress of 14.1mmHg (+/-1.1). Pulmonary
      artery pressure rose significantly in each of three subgroups (p<0.05). Stress
      echocardiography demonstrated PAH (using a cut-off of >35mmHg) in 59% of all
      individuals with systemic autoimmunity. CONCLUSION: Stress echocardiography is a
      useful tool in identifying individuals with autoimmune disease who may have
      underlying pulmonary arterial disease that may be amenable to therapy. We noted a
      consistent elevation in sPAP across all autoimmune subtypes, suggesting an
      abnormal pulmonary vascular response to exercise exists in these patients.

PMID- 16431162
TI  - Free-floating left atrial thrombus complicating mitral stenosis.
AB  - Free-floating thrombus is a rare disorder that usually occurs in the setting of a
      dilated left atrium. It is an important condition because it can produce sudden
      death by obstructing the mitral orifice or cause embolic events. Early diagnosis
      and surgical treatment are mandatory.

PMID- 16431160
TI  - Targeting vascular injury using Hantavirus-pseudotyped lentiviral vectors.
AB  - Restenosis is a pathological condition involving intimal hyperplasia and negative
      arterial remodeling. Gene therapy vectors have shown modest therapeutic effects,
      but the level of infectivity has been relatively poor. In the present study we
      have designed a modified lentiviral vector (LV) pseudotyped with a strain of
      Hantavirus (HTNV) to improve the transduction efficiency into vascular smooth
      muscle and endothelial cells in vitro and in vivo. In vivo studies using adult
      New Zealand White rabbits demonstrated that local delivery of HTNV-pseudotyped LV
      (2 x 10(7) TU) into balloon-injured carotid arteries led to highly efficient
      transduction into endothelial and smooth muscle cells more effectively than VSV-G
      pseudotyped LV (2 x 10(7) TU) or replication-defective adenoviral vectors (1-1.5
      x 10(9) pfu) as determined by beta-gal immunohistochemistry. Overexpression of
      extracellular superoxide dismutase in balloon-injured carotid arteries 6 weeks
      after LV administration resulted in a significant reduction (P = 0.0024) of the
      intima/media ratio (0.18 +/- 0.09; n = 4) compared to vehicle-infused carotid
      arteries (0.69 +/- 0.08; n = 7). No beta-gal immunostaining was detected in other
      systemic organs, including the spleen, liver, heart, lung, kidneys, and brain.
      Moreover, no changes in plasma alanine aminotransferase or aspartate
      aminotransferase were detected following LV administration. In all, these data
      show that LV pseudotyped with Hantaviral glycoproteins can be a useful vector for
      targeting therapeutic genes to the vasculature in vivo.

PMID- 16431163
TI  - A novel gene, Ami is expressed in vascular tissue in Xenopus laevis.
AB  - We report the isolation and expression pattern of a novel gene, Ami in Xenopus
      laevis. Ami was initially isolated as a highly expressed gene in cardiovascular
      tissues. The deduced amino acid sequence of Ami was most closely similar to human
      complement factor D and mouse adipsin in mammals. In adult Xenopus tissues, the
      transcript of Ami was detected in liver, fat body, lung, gut, vessel, heart,
      muscle, testis, and ovary, but expression in blood cells or skin was hardly
      detected. This expression profile was significantly different from that observed
      for mammalian homologues. Ami transcripts in Xenopus laevis were expressed from
      the late neurula stage, remained constant until the tadpole stage. The mRNA
      localized to paraxial regions at the neurula stage and anterior ventral regions
      at the tailbud stage. From the late tailbud to tadpole stage, expression was
      detected along the forming blood vessels, including the anterior cardinal veins,
      posterior cardinal veins, intersomitic veins, dorsal longitudinal anastomosing
      vessel, dorsal aorta, pronephric sinus, and most prominently around the vascular
      vitelline network. The expression around the vascular vitelline network
      demonstrated left-right asymmetry in stage 42 embryo. Comparison with the
      endothelium marker, Xmsr, suggested that Ami is expressed in endothelial cells.

PMID- 16431164
TI  - Escherichia coli-catalyzed bioelectrochemical oxidation of acetate in the
      presence of mediators.
AB  - Bioelectrocatalytic oxidation of acetate was investigated under anaerobic
      conditions by using Escherichia coli K-12 (IFO 3301) cells cultured on aerobic
      media containing poly-peptone, glucose or acetate as the sole carbon source. It
      was found that all E. coli cells cultured on the three media work as good
      catalysts of the electrochemical oxidation of acetate as well as glucose with
      Fe(CN)6(3-), 2,3-dimethoxy-5-methyl-1,4-benzo-quinone (Q0), 2,6-dichloro
      indophenol, or 2-methyl-1,4-naphthoquinone as artificial electron acceptors
      (mediators). Acetate-grown E. coli cells exhibited the highest relative activity
      of the acetate oxidation against the glucose oxidation. On the other hand, all
      the artificial electron acceptors used work as inhibitors for the catalytic
      oxidation of acetate at increased concentrations. The inhibition phenomenon can
      be interpreted in terms of competitive substrate inhibition as a whole. Apparent
      values of Michaelis constant, catalytic constant, and inhibition constant were
      evaluated by amperometric methods. Q0 is an effective artificial mediator as
      evidenced by a large reaction rate constant between the cell and Q0 at least at
      low concentrations (<50 microM). However, Fe(CN)6(3-) is a promising mediator in
      biosensor applications because the inhibition constant is very large and it works
      as an electron acceptor even under aerobic conditions.

PMID- 16431165
TI  - Dielectric spectroscopy of Anabaena 7120 protoplast suspensions.
AB  - The dielectric spectroscopy of Anabaena 7120 protoplast suspensions has been
      investigated over the frequency range of 40 Hz-110 MHz. The protoplast
      suspensions showed a complicated dielectric dispersion consisting of at least
      four distinct sub-dispersions with the increasing frequencies due to the Maxwell
      Wagner interfacial polarization. The double-shell model, in which an equivalent
      shell of thylakoid was assumed inside the cytoplasm, was adopted to describe the
      special morphology of the protoplast. Under the assumption that the conductivity
      of plasmalemma was negligible and the conductivity of the equivalent shell was
      0.1 microS/cm, we attempted to estimate the dielectric properties of various
      protoplast components by fitting theoretical curve to experimental data. The
      relative permittivity of the plasmalemma epsilon(mem) was estimated to be 6.5+/
      0.5, and the permittivity of the equivalent shell of thylakoid epsilon(thy) was
      estimated to be about 3.2+/-0.2. The permittivity epsilon(cyt) and conductivity
      kappa(cyt) of the cytoplasm were estimated to be 60 and 0.88+/-0.11 mS/cm,
      respectively. The permittivity epsilon(nuc) and conductivity kappa(nuc) of the
      nucleoplasmic region were determined to be 100 and 0.13+/-0.02 mS/cm,
      respectively.

PMID- 16431166
TI  - The honeycomb-like structure of the bird lung allows a uniquely thin blood-gas
      barrier.
AB  - Flying requires enormous energy and some birds have higher mass-specific maximal
      oxygen consumptions than any mammal. The bird lung is very efficient partly
      because of an extremely thin blood-gas barrier so that some birds have thinner
      barriers than any mammals. We show here that in addition to the total barrier
      being very thin, the interstitium which is responsible for the barrier's strength
      is extraordinarily thin. This observation is paradoxical because intense exercise
      raises the pressure in pulmonary capillaries and results in large stresses in the
      capillary walls thus predisposing them to structural failure. For example, all
      galloping racehorses break their pulmonary capillaries. We propose that the
      explanation for how the bird can be so highly energetic yet also have such
      apparently fragile capillaries is the mechanical support provided by the dense
      packing of rigid air capillaries around the blood capillaries in the gas
      exchanging region of the lung. This architecture is very different from that in
      the mammalian lung.

PMID- 16431167
TI  - Quantitative determination of latrunculins A and B in the Red Sea sponge
      Negombata magnifica by high performance liquid chromatography.
AB  - An accurate, reproducible and sensitive method for the quantitative determination
      of latrunculins A and B in the organic extract of the Red Sea sponge Negombata
      magnifica was developed and validated. Latrunculin A and B concentrations were
      determined by RP-C18-HPLC and a mobile phase consisting of acetonitrile and water
      (60:40, v/v). The flow rate utilized was 1 mL min(-1) and the detector was set at
      235 nm. The HPLC analysis of several N. magnifica samples collected from
      different locations in the Red Sea revealed that Ras Mohamed had the highest
      concentrations of latrunculin A, while Safaga had the highest levels of
      latrunculin B. Also, a comparison between latrunculin concentrations in the
      summer and winter revealed that the yield of latrunculins were generally higher
      in the winter.

PMID- 16431168
TI  - Quantitative evaluation of sphingolipids using delayed extraction matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry with
      sphingosylphosphorylcholine as an internal standard. Practical application to
      cardiac valves from a patient with Fabry disease.
AB  - Fabry disease is a glycolipid storage disorder caused by a defect of alpha
      galactosidase A, and characterized by the systemic deposition of
      glycosphingolipids with terminal alpha-galactosyl moieties, mainly
      globotriaosylceramide, in tissues. Using delayed extraction matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS), we
      analyzed the sphingolipids in the cardiac valves from a 49-year-old male patient
      with Fabry disease who suffered from congestive cardiac failure. Crude lipids
      were extracted from the cardiac valves with chloroform and methanol. After mild
      alkaline treatment of the crude lipids, a sphingolipid fraction was prepared and
      analyzed by DE MALDI-TOF-MS. The results were as follows: (a) ion peaks with m/z
      values corresponding to different ceramide trihexoside (CTH) species were
      detected; (b) with sphingosylphosphorylcholine (SPC) as the internal standard for
      semi-quantification of CTH, the relative peak height of CTH was calculated and
      plotted versus its amount loaded on the sample plate for MALDI-TOF-MS. The
      relative peak height of CTH with fatty acid C16:0 showed linearity between 0 and
      50 ng CTH (regression coefficient, r>0.95); (c) semi-quantitative analysis
      revealed striking accumulation of CTH in the cardiac valves from the patient with
      Fabry disease. It was indicated that the accumulation of CTH in cardiac valves
      from Fabry disease patients can be detected with the DE MALDI-TOF-MS method. SPC
      is commercially available, and this semi-quantitative method involving MALDI-TOF
      MS was found to be convenient, reliable and useful for CTH. It is expected to be
      applied to the quantification of CTH in small amounts of body fluids or other
      tissues and to clinical examination. It is also expected to be applicable to the
      quantification of other glycosphingolipids.

PMID- 16431169
TI  - Differential proteomic analysis of nuclear extracts from thyroid cell lines.
AB  - Nuclear proteins play a major role in controlling cell functions. Differential
      proteomic analysis of nuclear proteins by combined 2D gel electrophoresis (2D-E)
      and mass spectrometry procedures can provide useful information to understand the
      control of cell proliferation and differentiation. To identify proteins involved
      in dedifferentiation, we used a differential proteomics approach by comparing
      nuclear extracts from the differentiated rat thyroid cell line FRTL-5 and the
      derived undifferentiated Ki-mol cell line, obtained by transformation with the Ki
      ras oncogene. Thirteen proteins were identified as differently expressed in the
      nuclear compartment between the two cell lines. RT-PCR analysis performed on
      seven differently expressed genes showed that only in two cases the difference
      may be ascribable to a transcriptional mechanism. Since one of the identified
      proteins, namely apurinic apyrimidinic endonuclease/redox effector factor-1
      (APE1/Ref-1), is suspected to play a role in thyroid tumorigenesis, we used a
      glutathione S-transferase (GST)-pulldown assay coupled to a 2D
      electrophoretic/matrix assisted laser desorption ionization-time of flight (MALDI
      TOF)-mass spectrometry (MS) analysis to detect and identify its interacting
      partners. We show here that beta-actin directly interacted with APE1/Ref-1, as
      confirmed by co-immunoprecipitation assays and that this interaction was enhanced
      by oxidative stress on FRTL-5 cells.

PMID- 16431170
TI  - Roles of PKC, PI3K and JNK in multiple transduction of CCN2/CTGF signals in
      chondrocytes.
AB  - CCN2/connective tissue growth factor (CCN2/CTGF) is known to promote both the
      proliferation and differentiation of chondrocytes, which actions are mediated by
      ERK and p38 MAPK, respectively. In this study, we first re-evaluated the
      involvement of multiple MAPKs therein and found that JNK also mediated such CCN2
      signals. Thereafter, we further analyzed the roles of upstream kinases. The
      involvement of PKC, PI3K and PKA in the CCN2 signaling to promote the maturation,
      proliferation and terminal differentiation of a human chondrocytic cell line, HCS
      2/8 and rabbit primary growth cartilage cells was investigated. As a result, the
      PKC inhibitor calphostin C repressed all of the effects of CCN2, which were
      represented by increased synthesis of DNA and proteoglycans and the display of
      alkaline phosphatase activity. In addition, evaluation of the effect of the PI3K
      inhibitor wortmannin disclosed the contribution of PI3K in transducing CCN2
      signals to promote chondrocyte hypertrophy. This signal was known to be mediated
      by PKB, which was translocated into the nucleus upon CCN2 stimulation. Of note,
      calphostin C showed inhibitory effects on the activation of p38 MAPK, ERK and
      also PKB, whereas it exerted no effect on JNK activation. These results suggest
      that PKC is a driver of multiple signal transducing kinases that promote the
      proliferation and differentiation of chondrocytes. The requirement of PI3K in
      transmitting the signal for terminal differentiation and PKC-independent
      signaling pathways for the promotion of chondrocytic growth and differentiation,
      which was mediated by JNK, were also uncovered.

PMID- 16431171
TI  - Cancellous bone adaptation to in vivo loading in a rabbit model.
AB  - Biophysical stimuli are important to the development and maintenance of
      cancellous bone, but the regulatory mechanisms need to be understood. We
      investigated the effects of mechanical loading applied in vivo to native
      cancellous bone in the rabbit on bone formation and trabecular realignment. A
      novel device was developed to apply controlled compressive loads to cancellous
      bone in situ. The effect of loading on cancellous bone volume fraction and
      architecture was quantified. A 4-week experiment was performed in rabbits with
      devices implanted bilaterally. Cyclic 1 MPa pressures were applied daily to the
      right limb for 10, 25, or 50 cycles at 0.5 Hz, and the left limb served as the
      control without any applied loading. Microcomputed tomography and
      histomorphometry were used to characterize the cancellous tissue within a 4-mm
      spherical volume located below the loading core. In vivo cyclic loading
      significantly increased the bone volume fraction, direct trabecular thickness,
      mean intercept length, and mineral apposition rate in the loaded limbs compared
      with contralateral limbs. Insufficient evidence was found to demonstrate an
      effect of number of cycles on the cancellous adaptation between loaded and
      control limbs. Using a rabbit model, we demonstrated that mechanical loading
      applied to cancellous bone in situ increased bone formation and altered
      trabecular morphology. This in vivo model will allow further investigation of
      cancellous functional adaptation to controlled mechanical stimuli and the
      influence of mechanical loading parameters, metabolic status, and therapeutic
      agents.

PMID- 16431172
TI  - Clinical confidence and the three C's: caring, communicating, and competence.

PMID- 16431173
TI  - Engaged mentors offer inspiration and open doors.

PMID- 16431174
TI  - Good news from Lake Wobegon.

PMID- 16431175
TI  - Cardiocerebral resuscitation for cardiac arrest.
AB  - Survival rates from out-of-hospital cardiac arrest continue to be low despite
      periodic updates in the Guidelines for Emergency Medical Services and periodic
      improvements such as the addition of automatic external defibrillators (AEDs).
      The low incidence of bystander cardiopulmonary resuscitation (CPR), substantial
      time without chest compressions throughout the resuscitation effort, and a lack
      of response to initial defibrillation after prolonged ventricular fibrillation
      contribute to these unacceptably poor results. Resuscitation guidelines are only
      revised every 5 to 7 years and can be difficult to change because of the lack of
      randomized controlled trials in humans. Such trials are rare because of a number
      of logistical difficulties, including the problem of obtaining informed consent.
      An alternative approach to advancing resuscitation science is for evidence-based
      demonstration projects in areas that have adequate records, so that one may
      determine whether the new approach improves survival. This is reasonable because
      the current guidelines make provisions for deviations under certain local
      circumstances or as directed by the emergency medical services medical director.
      A wealth of experimental evidence indicates that interruption of chest
      compressions for any reason in patients with cardiac arrest is deleterious.
      Accordingly, a new approach to out-of-hospital cardiac arrest called
      cardiocerebral resuscitation (CCR) was developed that places more emphasis on
      chest compressions for witnessed cardiac arrest in adults and de-emphasizes
      ventilation. There is also emphasis on chest compressions before defibrillation
      in circulatory phase of cardiac arrest. CCR was initiated in Tucson, Arizona, in
      November 2003, and in two rural Wisconsin counties in early 2004.

PMID- 16431176
TI  - Transient left ventricular dysfunction under severe stress: brain-heart
      relationship revisited.
AB  - PURPOSE: Transient left ventricular dysfunction in patients under emotional or
      physical stress, also known as tako-tsubo-like left ventricular dysfunction, has
      been recently been recognized as a distinct clinical entity. The aims of this
      review are to define this phenomenon and to explore its similarities to the left
      ventricular dysfunction seen in patients with acute brain injury. METHODS:
      MEDLINE database, bibliographies of each citation for relevant articles, and
      consultation with clinical experts were used to examine the clinical picture of
      tako-tsubo-like left ventricular dysfunction. RESULTS: We identified case series
      and a systematic review that report on patients with this syndrome. This
      phenomenon occurs predominantly in female patients, presenting with a variety of
      ST-T segment changes and mildly elevated cardiac enzymes that mimic an acute
      coronary syndrome. The left ventricular dysfunction, typically showing a
      hyperkinetic basal region and an akinetic apical half of the ventricle, occurs in
      the absence of obstructed epicardial coronary arteries. The ventricular
      dysfunction usually resolves within weeks with a generally favorable prognosis.
      This phenomenon has similarities to that seen in patients with acute brain injury
      with regard to clinical presentation, pathology, and its reversible nature.
      CONCLUSIONS: Transient left ventricular dysfunction occurs in the absence of
      obstructive epicardial coronary artery disease. In its broadest sense, this
      phenomenon may encompass a range of disorders including left ventricular
      dysfunction after central nervous system injury.

PMID- 16431177
TI  - Echocardiography and reversible left ventricular dysfunction.
AB  - PURPOSE: Transient apical ballooning is increasingly recognized in acutely ill,
      hospitalized patients. This article reviews clinical aspects of the syndrome, its
      recognition by echocardiography, and will review other disorders whose
      recognition is due primarily to the availability of echocardiography. METHODS:
      Systematic review of the medical literature concerning the syndrome of transient
      apical ballooning. RESULTS: Seven recent studies of transient apical ballooning
      are reviewed; the clinical characteristics, biomarker data, echocardiographic
      findings, and angiographic data are remarkably similar. Most afflicted
      individuals are women in their seventh decade who develop chest symptoms in close
      relationship to a "trigger" event--this is usually either severe emotional
      distress, a medical illness, or a procedure. CONCLUSIONS: Transient apical
      ballooning is not uncommonly encountered among acutely ill, hospitalized patients
      with chest symptoms. As yet there is no consensus of the underlying mechanism,
      although there is reason to believe that catecholamine injury to the myocardium
      is partially, if not wholly responsible. The widespread use of echocardiography
      appears to be responsible for the increasing recognition of this (and other)
      syndromes.

PMID- 16431179
TI  - All in the family.

PMID- 16431178
TI  - Management of psychiatric problems in critically ill patients.
AB  - Critical care units have become essential elements in modern medicine. These
      units reflect the highest levels of scientific and technological advance in
      medicine. Within these units, however, lie significant psychiatric challenges for
      patients and staff. This article examines the identification and treatment of the
      most frequent psychiatric problems facing patients entering critical care units,
      including delirium, depression and anxiety. These conditions are important to
      address in order to decrease patient suffering and improve morbidity and
      mortality. The article also addresses some of the most common staff stressors
      encountered in working in these units. Managing these stressors makes the
      critical care unit a place where staff can flourish instead of burning out.
      Specific techniques may help the staff deal with the complex medical,
      psychological, and ethical issues found in these units in an empathic,
      compassionate, and well-balanced manner that allows ongoing work satisfaction.

PMID- 16431180
TI  - Multiple yellow plaques of the eyelids.

PMID- 16431181
TI  - An extraordinary case?

PMID- 16431182
TI  - Young man with asymptomatic lung cysts.

PMID- 16431183
TI  - Trends in blood pressure, hypertension control, and stroke mortality: the
      Minnesota Heart Survey.
AB  - OBJECTIVE: The study's objective was to determine population trends in blood
      pressure, hypertension prevalence, hypertension control, and stroke mortality.
      METHODS: We performed population-based surveys of 2906 to 5630 adults from 1980
      to 1982, 1985 to 1987, 1990 to 1992, 1995 to 1997, and 2000 to 2002, and stroke
      mortality from 1980 to 2002, in the Minneapolis/St Paul, Minn metropolitan area
      (2.63 million population according to the 2000 census). Randomly selected
      resident adults aged 25 to 74 years (n = 21773) were each screened once. The main
      outcome measures were standardized measures of blood pressure, treatment and
      control of hypertension, and stroke mortality rates. RESULTS: The mean systolic
      blood pressure adjusted for age decreased in men (-1.5 mm Hg [95% confidence
      interval -0.3 to -2.7], P <.01) and women (-1.8 mm Hg [95% confidence interval 
      0.5 to -3.0], P <.001) from 1980 to 1982 and 2000 to 2002. The mean diastolic
      blood pressure was unchanged for men (0 mm Hg) and women (-0.4 mm Hg, not
      significant). The proportion of the population taking antihypertensive
      medications decreased in the 1990s but returned to 1980s levels from 2000 to
      2002. The use of other methods to decrease blood pressure (diet, exercise, and
      weight loss) peaked in the 1990 to 1992 survey and then decreased. Proportions of
      hypertensive patients in the aware, treated, and/or controlled categories leveled
      in the 1980s and 1990s, but improved substantially from 1995 to 1997 and 2000 to
      2002 with blood pressure controlled at the less than 140 and/or 90 mm Hg criteria
      in 44% of the men and 55% of the women. Population mortality trends for stroke
      paralleled those for hypertension control. CONCLUSIONS: Population data beginning
      in 1980 to 1982 from the Minnesota Heart Survey indicate a leveling in the
      detection and control of hypertension in the 1990s followed by improvement from
      2000 to 2002.

PMID- 16431184
TI  - Family history for venous thromboembolism and the risk for recurrence.
AB  - PURPOSE: The relevance of a family history for venous thromboembolism with regard
      to the likelihood for recurrence is unknown. SUBJECTS AND METHODS: We studied 826
      patients for an average of 36 months after a first unprovoked venous
      thromboembolism and withdrawal of oral anticoagulation. Patients with cancer,
      lupus anticoagulant, or deficiency of antithrombin, protein C, or protein S were
      excluded. The study endpoint was objective evidence of recurrent symptomatic
      venous thromboembolism. RESULTS: Recurrence for venous thromboembolism was
      recorded in 23 of 190 patients (12.1%) with a family history (at least one
      affected first-degree family member) and in 79 of 636 patients (12.4%) without
      familial thrombosis (relative risk for recurrence 1.0; 95% confidence interval,
      0.7-1.6; P=.9). At 5 years, the likelihood for recurrence was 20% among patients
      with a family history for venous thromboembolism and 18% among those without a
      family history for venous thromboembolism (P=.9). Risk determinants for venous
      thromboembolism including factor V Leiden, factor II G20210A, and high factor
      VIII were not statistically different between the 2 groups. CONCLUSION: A family
      history for venous thromboembolism does not segregate patients into high- or low
      risk categories and is not suitable to identify patients at increased risk for
      recurrent venous thromboembolism.

PMID- 16431185
TI  - The prophylaxis of medical patients for thromboembolism pilot study.
AB  - PURPOSE: We assessed the feasibility of a large randomized trial intended to
      determine whether low-dose heparin prophylaxis given throughout hospitalization
      reduces mortality and morbidity in general medical patients. SUBJECTS AND
      METHODS: Hospitalized general medical patients aged more than 60 years at 5
      Department of Veterans Affairs (VA) medical centers were randomized to receive
      enoxaparin 40 mg or identical placebo, given daily by subcutaneous injection
      until hospital discharge. Outcomes included total mortality at 90 days (the
      primary outcome) and 1 year, and occurrence in the VA hospital within 90 days of
      symptomatic deep venous thrombosis, pulmonary embolism, and major bleeding.
      RESULTS: Only 7.6% of hospitalized patients aged more than 60 years were eligible
      for the study, although a chart review had predicted 25%. The principal
      exclusions were prior indication for anticoagulation, anticipated need for
      anticoagulation, contraindication to heparin, expected hospitalization less than
      3 days, and "supportive/palliative care only" status. We randomized 140 patients
      into each group, 28% of target recruitment. The groups were well matched by age
      and comorbidities. Death occurred in 13 patients receiving enoxaparin and 14
      patients receiving placebo at 90 days (relative risk 0.93, 95% confidence
      interval 0.26-1.59), and in 36 and 32 patients, respectively, at 1 year (relative
      risk 1.13, 95% confidence interval 0.66-1.60). Clinical thromboembolic events
      occurred in 5 patients receiving enoxaparin and 8 patients receiving placebo, and
      major bleeding occurred in 2 and 5 patients, respectively. CONCLUSIONS: The pilot
      study indicated that the full study was not feasible. The decision to use
      prophylaxis pertains to only a small proportion of general medical patients
      hospitalized at VA medical centers, and this proportion is overestimated by chart
      review. The effect of low-dose heparin prophylaxis on clinical outcomes in
      hospitalized general medical patients remains uncertain.

PMID- 16431186
TI  - Incidence of venous thromboembolism in patients hospitalized with cancer.
AB  - BACKGROUND: There are sparse data on the frequency of venous thromboembolism in
      patients with various types of cancer. We sought to determine the incidence and
      relative risk of venous thromboembolism, pulmonary embolism, and deep venous
      thrombosis in patients with malignancies. SUBJECTS AND METHODS: The number of
      patients discharged with a diagnostic code for 19 types of malignancies,
      pulmonary embolism or deep venous thrombosis from 1979 through 1999 was obtained
      from the National Hospital Discharge Survey. Patients studied were men and women
      of all ages and races. RESULTS: In patients with any of the 19 malignancies
      studied, 827,000 of 40,787,000 (2.0%) had venous thromboembolism, which was twice
      the incidence in patients without these malignancies, 6,854,000 of 662,309,000
      (1.0 %). The highest incidence of venous thromboembolism was in patients with
      carcinoma of the pancreas, 51,000 of 1,176,000 (4.3%), and the lowest incidences
      were in patients with carcinoma of the bladder and carcinoma of the lip, oral
      cavity or pharynx. The overall incidences of pulmonary embolism and deep venous
      thrombosis were also twice the rates in noncancer patients. Incidences with
      cancer were not age dependent. The incidence of venous thromboembolism in
      patients with cancer began to increase in the late 1980s. CONCLUSION: Patients
      with cancer had twice the incidence of venous thromboembolism, pulmonary embolism
      and deep venous thrombosis as patients without cancer. The incidence of venous
      thromboembolism, pulmonary embolism and deep venous thrombosis associated with
      cancer differed according to the type of cancer, was comparable in elderly and
      younger patients, and increased in the late 1980s and 1990s.

PMID- 16431187
TI  - Impact of the history of congestive heart failure on the utility of B-type
      natriuretic peptide in the emergency diagnosis of heart failure: results from the
      Breathing Not Properly Multinational Study.
AB  - PURPOSE: B-type natriuretic peptide is known to correlate with hemodynamic state,
      presence and severity of congestive heart failure, and prognosis. Although low
      range B-type natriuretic peptide less than 100 pg/mL has a high negative
      predictive value (90%), and high-range B-type natriuretic peptide greater than
      500 pg/mL has a high positive predictive value (87%), there remains some
      ambiguity in the interpretation of results in the medium range (100-500 pg/mL).
      We hypothesized that taking into account the history of congestive heart failure
      along with other clinical variables would be helpful in this range of B-type
      natriuretic peptide levels. METHOD: The Breathing Not Properly Multicenter Study
      was an international, 7-center, prospective study including 1475 patients with a
      mean age of 63 years (57% were male, and 54% were female); 35% of patients with a
      history of congestive heart failure were enrolled, and a final diagnosis of
      congestive heart failure was made in 46%. The index criteria was defined as
      positive if any 2 index findings (ie, history of coronary artery disease, lower
      extremity edema, pulmonary edema, cephalization of the pulmonary arteries, and
      cardiomegaly) were present. RESULTS: The interval likelihood ratios (LR) for low,
      medium, and high B-type natriuretic peptide ranges are 0.13, 1.85, and 8.1,
      respectively. For medium B-type natriuretic peptide levels a positive history of
      congestive heart failure makes the diagnosis of congestive heart failure more
      probable with a cumulative LR of 4.3. Also in this range a positive index
      criterion was strongly indicative of congestive heart failure even in the absence
      of a history of congestive heart failure (LR 3.3). Where there are both a
      positive history of congestive heart failure and a positive index criteria for
      the medium B-type natriuretic peptide group, the cumulative LR (10.2) is similar
      to that of a high B-type natriuretic peptide level (8.1). CONCLUSION: Even in the
      medium range (100-500 pg/mL), when using the history of congestive heart failure
      and index criteria, B-type natriuretic peptide can be a powerful diagnostic tool
      in the hands of clinicians in the emergency department.

PMID- 16431188
TI  - Normal ambulatory blood pressure: a clinical-practice-based analysis of recent
      American Heart Association recommendations.
AB  - PURPOSE: The American Heart Association Council on High Blood Pressure Research
      recently issued recommendations for blood pressure measurement in humans.
      According to these recommendations, normal 24-hour ambulatory blood pressure is
      defined as less than 130/80 mm Hg. Concurrently, normal daytime and nighttime
      blood pressure levels are defined as less than 135/85 mm Hg and less than 120/70
      mm Hg, respectively. Our aim was to investigate the intrinsic compatibility of
      these blood pressure cutoffs in clinical practice. SUBJECTS AND METHODS: We
      analyzed 4121 consecutive ambulatory blood pressure measurement sessions. Age was
      57 +/- 7 years, 53% were female, and 64% and 9% were treated for hypertension and
      diabetes, respectively. Body mass index was 27 +/- 4 kg/m2, and manual blood
      pressure was 148 +/- 22/85 +/- 12 mm Hg. Subjects were classified as having
      normal 24-hour blood pressure if the corresponding value was less than 130/80 mm
      Hg. Normal awake-sleep blood pressure was diagnosed if awake blood pressure was
      less than 135/85 mm Hg and sleep blood pressure was less than 120/70 mm Hg.
      RESULTS: Concordance between the cutoffs was found in 92% of the subjects (kappa
      = 0.77). Among the 8% of discordant subjects, only 1% were hypertensive applying
      the 24-hour (but not awake-sleep) blood pressure values, whereas 7% were
      hypertensive according to awake-sleep but not 24-hour blood pressure values (P
      <.0001). CONCLUSIONS: In real-life ambulatory blood pressure measurement, a
      generally good agreement was found between the recently issued ambulatory blood
      pressure normality suggestions. However, some subjects are classified as
      hypertensive only according to one of these methods, more often by the awake
      sleep cutoff of 135/85 and 120/70 mm Hg. This discordance may be significant in
      large-scale clinical blood pressure monitoring.

PMID- 16431190
TI  - Routine blood pressure measurements do not predict adverse events in hospitalized
      patients.
AB  - PURPOSE: Countless blood pressure measurements are performed every day for almost
      every hospitalized patient. We analyzed the value of routine blood pressure
      measurements on patient care in an unselected group of hospitalized patients.
      METHODS: The study included 639 patients who were admitted to the hospital with a
      broad range of medical conditions. Two independent investigators reviewed the
      medical charts of the patients. Routine blood pressure values were abstracted
      from the patient charts and evaluated with respect to the occurrence of adverse
      clinical events in the study group. Changes in blood pressure between the last
      measurement just before adverse clinical events and the mean blood pressure
      values 72 hours before the adverse events were calculated and compared with mean
      normal day-to-day variations in blood pressure. RESULTS: In every patient, a mean
      of 1.6 +/- 0.6 routine blood pressure measurements per day were performed. Of the
      639 patients in the study, 122 (19%) had clinical complications. The most
      commonly occurring complications were gastrointestinal bleeding (n = 15), falls
      (n = 13), other bleeding (n = 12) and pneumonia (n = 8). In patients who
      experienced clinical complications, pre-event systolic and diastolic blood
      pressure changes of at least 10 mm Hg occurred in 41% and 24% of the group,
      respectively, but this was not different from the normal day-to-day variations
      observed in patients who had no clinical complications. The results also were
      similar for patients who died or who had a severe adverse event that required
      admission to an intensive care unit. CONCLUSION: Routine blood pressure
      measurements in a general hospital patient population do not predict clinical
      adverse events.

PMID- 16431189
TI  - Differences in the clinical features and outcomes in African Americans and whites
      with myocardial infarction.
AB  - PURPOSE: Less is known about the differences in clinical and angiographic
      features and the outcomes of African Americans with ST-elevation myocardial
      infarction compared with whites with ST-elevation myocardial infarction.
      Accordingly, the current study examines the relationship of African American race
      to patient-related clinical factors, angiographic findings, and clinical events.
      METHODS: We evaluated data from 32419 patients with ST-elevation myocardial
      infarction who received fibrinolysis. The primary outcomes of interest were 30
      day and 5-year mortality. RESULTS: African Americans comprised 5.1% of the study
      population (1664/32419). Compared with white patients, black patients were
      younger, were more likely female, had a higher prevalence of coronary risk
      factors, and were more likely to have higher presenting heart rate, blood
      pressure, and Killip Class. Coronary angiography rates were similar in the two
      groups, but blacks were less likely to undergo coronary revascularization. The
      patency of the infarct-related artery after thrombolysis or mechanical
      reperfusion was higher in blacks, who were more likely to have no significant
      coronary artery disease and less likely to have disease in two or more vessels.
      In-hospital stroke (adjusted odds ratio 1.75, 95% confidence interval [CI] 1.19
      2.59) and major bleeding (adjusted odds ratio 1.32, 95% CI 1.13-1.55) were higher
      among African Americans. Although no differences were observed in the 30-day
      mortality between the two groups, African Americans who survived to 30 days had
      higher 5-year mortality than whites (17% vs 12.5%, adjusted hazard ratio 1.63,
      95% CI 1.41-1.90). CONCLUSIONS: Although 30-day survival was similar between
      African Americans and whites with ST-elevation myocardial infarction, in-hospital
      stroke and bleeding and 5-year mortality among 30-day survivors were
      significantly higher among blacks despite their younger age.

PMID- 16431191
TI  - Incremental prognostic value of changes in B-type natriuretic peptide in heart
      failure.
AB  - PURPOSE: B-type natriuretic peptide is one of the most sensitive and specific
      biohumoral markers of heart failure. We hypothesized that B-type natriuretic
      peptide changes during treatment of heart failure may provide independent
      information on disease progression and outcome in patients enrolled in the Val
      HeFT trial. METHODS: Patients were divided into four groups according to
      concentrations of B-type natriuretic peptide at baseline versus 4 months (n =
      3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL):
      low-->low (stable below median, 44%-46%), high-->high (stable above median, 32%
      37%), high-->low (above to below median, 12%-14%), and low-->high (below to above
      median, 6%-9%). Cox multivariate regression analysis was used to assess the risk
      of death and morbidity, with adjustment for baseline B-type natriuretic peptide
      concentrations. RESULTS: Patients who improved their B-type natriuretic peptide
      at 4 months (high-->low) had a similar risk for mortality (hazard ratio = 1.191,
      95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low-->low
      patients. Conversely, patients who worsened in their B-type natriuretic peptide
      (low-->high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P
      <.0001) higher than patients in the low-->low group, and indistinguishable from
      the high-->high group. Worsening of B-type natriuretic peptide (low-->high) was
      associated with 0.03 cm/m2 increase in left ventricular end-diastolic diameter,
      whereas it decreased by 0.10 cm/m2 in high-->low and low-->low groups (P <.001).
      CONCLUSIONS: Changes in B-type natriuretic peptide over time with respect to a
      threshold value of 97 pg/mL convey an independent and additional prognostic value
      compared with a single determination of B-type natriuretic peptide in a large
      population of patients with chronic symptomatic heart failure and might be
      helpful in the management of these patients.

PMID- 16431192
TI  - Racial differences in blood pressure control: potential explanatory factors.
AB  - PURPOSE: Poor blood pressure control remains a common problem that contributes to
      significant cardiovascular morbidity and mortality, particularly among African
      Americans. We explored antihypertensive medication adherence and other factors
      that may explain racial differences in blood pressure control. METHODS: Baseline
      data were obtained from the Veteran's Study to Improve The Control of
      Hypertension, a randomized controlled trial designed to improve blood pressure
      control. Clinical, demographic, and psychosocial factors relating to blood
      pressure control were examined. RESULTS: A total of 569 patients who were African
      American (41%) or white (59%) were enrolled in the study. African Americans were
      more likely to have inadequate baseline blood pressure control than whites (63%
      vs 50%; odds ratio = 1.70; 95% confidence interval [CI] 1.20-2.41). Among 20
      factors related to blood pressure control, African Americans also had a higher
      odds ratio of being nonadherent to their medication, being more functionally
      illiterate, and having a family member with hypertension compared with whites.
      Compared with whites, African Americans also were more likely to perceive high
      blood pressure as serious and to experience the side effect of increased
      urination compared with whites. Adjusting for these differences reduced the odds
      ratio of African Americans having adequate blood pressure control to 1.59 (95%
      confidence interval 1.09-2.29). CONCLUSIONS: In this sample of hypertensive
      patients who have good access to health care and medication benefits, African
      Americans continued to have lower levels of blood pressure control despite
      considering more than 20 factors related to blood pressure control. Interventions
      designed to improve medication adherence need to take race into account.
      Patients' self-reports of failure to take medications provide an opportunity for
      clinicians to explore reasons for medication nonadherence, thereby improving
      adherence and potentially blood pressure control.

PMID- 16431193
TI  - Mild chronic hyponatremia is associated with falls, unsteadiness, and attention
      deficits.
AB  - OBJECTIVE: The study objective was to determine the eventual consequences (falls,
      unsteadiness, and cognitive impairment) of mild chronic hyponatremia, which is
      generally considered as asymptomatic. METHODS: In a case-control study, we
      focused on the incidence of falls among 122 patients (mean age 72+/-13 years)
      with asymptomatic chronic hyponatremia (mean serum sodium concentration [SNa]
      126+/-5 mEq/L), who were admitted to the medical emergency department, compared
      with 244 matched controls. To explore the mechanisms of the excess of falls, we
      prospectively asked 16 comparable patients (mean age 63+/-15 years; SNa+/-2
      mEq/L) to perform 8 attention tests and a gait test consisting of 3 steps "in
      tandem," in which we measured the "total traveled way" by the center of pressure
      or total traveled way. Thereafter, the patients were treated and tested again
      (50% of the patients were tested first with normal SNa to avoid learning biases).
      RESULTS: Epidemiology of falls: Twenty-six patients (21.3%) of 122 were admitted
      for falls, compared with only 5.3% of the control patients (adjusted odds ratio:
      67; 95% confidence: 7.5-607; P <.001). The frequency of falls was the same
      regardless of the level of hyponatremia. Gait: The total traveled way by the
      center of pressure significantly increased in hyponatremia (1336+/-320 mm vs
      1047+/-172 mm with normal SNa; P=.003). Attention tests: The mean response time
      was 673+/-182 milliseconds in hyponatremia and 615+/-184 milliseconds in patients
      with normal SNa (difference: 58 milliseconds, P <.001). The total error number in
      hyponatremia increased 1.2-fold (P=.001). These modifications were comparable to
      those observed after alcohol intake in 10 volunteers. CONCLUSIONS: Mild chronic
      hyponatremia induces a high incidence of falls possibly as the result of marked
      gait and attention impairments. Treating these patients might prevent a
      considerable number of hospitalizations.

PMID- 16431194
TI  - Beyond the comfort zone: residents assess their comfort performing inpatient
      medical procedures.
AB  - PURPOSE: Resident physicians learn to perform inpatient bedside procedures in a
      manner that is neither standardized nor rigorous. As a result, residents may be
      unskilled and uncomfortable performing procedures. This study characterizes
      residents' comfort performing medical procedures and identifies factors
      associated with lack of comfort. SUBJECTS: Study subjects were internal medicine
      resident physicians who performed one of four medical procedures (central line,
      lumbar puncture, paracentesis, or thoracentesis) on adult medical inpatients
      between July 1, 2003, and June 30, 2004. METHODS: This prospective cohort study
      was conducted at a 556-bed Boston teaching hospital. Resident physicians
      evaluated their comfort with 9 aspects of 4 medical procedures, recording this
      information in an electronic log. We also abstracted operator characteristics and
      patient demographic data. We analyzed residents' comfort with each aspect of the
      procedure and defined "overall comfort" as comfort with each of the 9 aspects.
      RESULTS: A majority of resident physicians reported lack of comfort with at least
      one aspect of the procedure. Residents reported lack of comfort with 37% of
      unsupervised procedures. They also reported lack of comfort with the prospect of
      managing complications in 35% of procedures. In the multivariable analysis,
      overall comfort was associated with the use of a dedicated medical procedure
      service (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.4) and inversely
      associated with postgraduate year 1 status (OR 0.3, CI 0.1-0.5), first time
      performing the procedure (OR 0.4, CI 0.2-0.8), thoracenteses (OR 0.4, CI 0.2
      0.8), and emergent procedures (OR 0.6, CI 0.3-1.0). CONCLUSIONS: Many resident
      physicians are uncomfortable performing common bedside procedures. Experience and
      supervision mitigate some, but not all, discomfort.

PMID- 16431195
TI  - Long-term outcome after hepatitis B surface antigen seroclearance in patients
      with chronic hepatitis B.
AB  - PURPOSE: The aim of this study was to elucidate the long-term outcome after
      hepatitis B surface antigen (HBsAg) seroclearance in a large number of Japanese
      patients. METHODS: We studied the biochemical, virologic, histologic, and
      prolonged prognoses of 231 Japanese patients with HBsAg seroclearance (median
      follow-up, 6.5 years). Serum alanine aminotransferase, serum hepatitis B virus
      (HBV) markers, liver histology, and clinical aspects were monitored. HBV-DNA
      levels were measured with the qualitative polymerase chain reaction assay. The
      mean age of patients with HBsAg seroclearance was 52 years. RESULTS: After HBsAg
      seroclearance, 203 patients (87.9%) had normal alanine aminotransferase levels 1
      year after HBsAg seroclearance. HBV-DNA showed positive results in 4 patients
      (1.7%) 1 year after HBsAg seroclearance. Thirteen patients were examined for
      histologic changes of the liver after HBsAg seroclearance. All patients showed
      marked improvement of necroinflammation of the liver, but only 2 of the 13
      patients showed no liver fibrosis. Liver cirrhosis and hepatocellular carcinoma
      did not develop in any of the 164 patients without evidence of liver cirrhosis at
      the time of HBsAg seroclearance. Hepatocellular carcinoma developed in 2 of the
      67 patients with liver cirrhosis at the time of HBsAg seroclearance. During the
      observation period, 15 patients died. However, the cause of death of these 15
      patients was not related to liver disease, such as hepatocellular carcinoma,
      decompensated liver cirrhosis, and rupture of esophageal varices. CONCLUSION: Our
      results suggest that HBsAg seroclearance confers favorable long-term outcomes in
      patients without hepatocellular carcinoma or decompensated liver cirrhosis at the
      time of HBsAg seroclearance.

PMID- 16431196
TI  - Hospital medicine fellowships: works in progress.
AB  - The field of hospital medicine continues to grow rapidly, and with this growth
      has come the realization that residency alone may not provide the full complement
      of skills required of a successful hospitalist. As a result, several institutions
      have started hospitalist fellowships, new programs with the specific goal of
      training clinicians to improve hospital care. These fellowships offer diverse
      approaches to preparation for a hospitalist career, with opportunities for
      advanced training in clinical care, teaching, research, and quality improvement.
      This article provides an overview of the programs, explores the choices for
      trainees in selecting a fellowship, and the challenges for institutions in
      developing a new fellowship. Although hospitalist fellowships are still in
      evolution, they will play an important role in the development of hospital
      medicine.

PMID- 16431198
TI  - The power of repetition in mastering cardiac auscultation.

PMID- 16431199
TI  - Achieving diversity in academic internal medicine: recommendations for leaders.

PMID- 16431197
TI  - Aging influences on pharyngeal anatomy and physiology: the predisposition to
      pharyngeal collapse.

PMID- 16431200
TI  - Bleeding of small bowel in Henoch-Schonlein syndrome: the successful diagnostic
      role of video capsule endoscopy.

PMID- 16431201
TI  - Henoch-Schonlein purpura associated with methicillin-resistant Staphylococcus
      aureus infection.

PMID- 16431203
TI  - Can pregnancy stop cyclical attacks of porphyria?

PMID- 16431202
TI  - Rituximab in postpartum-related acquired hemophilia.

PMID- 16431204
TI  - New evidence for high occurrence of olfactory dysfunctions within the population.

PMID- 16431205
TI  - Invasive management for patients with NSTE-ACS.

PMID- 16431207
TI  - Reply to the Vioxx debacle.

PMID- 16431206
TI  - Reply to "Viagra: the risks of recreational use".

PMID- 16431208
TI  - Mechanical ventilation learns new tricks.

PMID- 16431209
TI  - Alcohol consumption and cognitive function in patients with heart failure.

PMID- 16431211
TI  - Prevalence of elevated ankle-brachial index.

PMID- 16431214
TI  - Deep venous thrombosis before patent foramen ovale closure.

PMID- 16431215
TI  - A writer well-versed in patient care.

PMID- 16431217
TI  - Human adiponectin binds to bacterial lipopolysaccharide.
AB  - Adiponectin has anti-inflammatory and anti-atherogenic properties in addition to
      its acknowledged roles in insulin sensitivity and energy homeostasis. These
      properties include the suppression of lipopolysaccharide [LPS]-mediated
      inflammatory events. We demonstrated that both recombinant and native adiponectin
      directly bind LPS derived from three different bacteria. The interaction occurred
      at pH 5.0-6.0 and was inhibited by the presence of Ca(2+) and Mg(2+), but
      enhanced by the sequestration of these cations. Maximal binding occurred at pH
      6.0 in the presence of ethylenediaminetetraacetic acid. Lipid A and C1q were not
      inhibitory, although LPS, heparin, zymosan, and individual sugars all inhibited
      the reaction. Periodate-mediated deglycosylation of adiponectin, and reduction
      and alkylation also inhibited binding. Since adiponectin infiltrates into
      [relatively] acidic sites of inflammation, it may act as a scavenging anti
      inflammatory agent in atherosclerosis and vascular damage where LPS [and other
      pro-inflammatory molecules] are present.

PMID- 16431216
TI  - A novel substitution at the translation initiator codon (ATG-->ATC) of the
      lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency
      in a patient with severe hypertriglyceridemia and recurrent pancreatitis.
AB  - A patient with severe hypertriglyceridemia and recurrent pancreatitis was found
      to have significantly decreased lipoprotein lipase (LPL) activity and normal
      apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL
      gene revealed two mutations, one of which was a novel homozygous G-->C
      substitution, resulting in the conversion of a translation initiation codon
      methionine to isoleucine (LPL-1). The second was the previously reported
      heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242).
      In vitro expression of both mutations separately or in combination demonstrated
      that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had
      undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited
      similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with
      undetectable activity. These results suggest that the homozygous initiator codon
      mutation rather than the heterozygous LPL-242 alteration was mainly responsible
      for the patient phenotypes.

PMID- 16431218
TI  - A single amino-acid change in ERK1/2 makes the enzyme susceptible to PP1
      derivatives.
AB  - We generated extracellular signal-regulated kinase 1/2 (ERK1/2) mutants by
      introducing a single amino-acid substitution in subdomain V of the catalytic
      domain and then examined the susceptibility of these mutants to PP1 derivatives
      originally designed as Src inhibitors. Substituting smaller amino acids (alanine
      [Ala (A)] or glycine [Gly (G)]) for glutamine [Gln (Q)] in subdomain V
      drastically increased the susceptibility of ERK1/2 to 1-naphthyl PP1 (1NA-PP1).
      Wild-type ERK1/2 was resistant to 1NA-PP1 inhibition. ERK1(Q122A) and ERK2(Q103A)
      were inhibited by 1NA-PP1 at IC(50) values of 1.7 +/- 0.13 and 2.1 +/- 0.18
      microM, respectively. ERK1(Q122G) and ERK2(Q103G) were inhibited by 1NA-PP1 with
      IC(50) values of 3.6 +/- 0.26 and 18 +/- 2.2 microM, respectively. Other
      derivatives of PP1 (1-naphthylmethyl PP1 and 2-naphthylmethyl PP1) did not
      significantly inhibit ERK1/2 and its various mutants. In addition, these ERK1/2
      mutants were activated by TPA when they were expressed in mammalian cells. These
      results suggest that the Gln residue of subdomain V is important in determining
      the susceptibility of ERK1/2 to 1NA-PP1 without significant changes in their
      enzymatic characteristics.

PMID- 16431219
TI  - Corticosterone-induced inhibition of gliogenesis in rat hippocampus is
      counteracted by electroconvulsive seizures.
AB  - BACKGROUND: Volumetric changes and glial pathology have been reported in the
      central nervous system (CNS) of patients with depressive disorder, an illness
      often associated with elevated glucocorticoid levels. Glucocorticoids reduce
      gliogenesis in the adult rat CNS. Electroconvulsive seizure (ECS)-treatment, an
      animal model for the antidepressant treatment electroconvulsive therapy, can
      enhance proliferation of glial cells. This study examined glial cell
      proliferation in response to ECS in rats whose glucocorticoid levels were
      elevated to mimic the conditions seen in depression. METHODS: Rats were injected
      daily for seven days with either corticosterone or vehicle. ECS- or sham-
      treatment was given once daily during the first five days. Proliferating cells in
      the hippocampus were labeled with bromodeoxyuridine and analyzed for co-labeling
      with the glial cell markers NG2, Ox42, S-100beta and Rip. RESULTS: ECS
      counteracted the glucocorticoid-induced inhibition of NG2+, Ox42+ and Rip+ cell
      proliferation, and the gliogenesis rate was restored to baseline levels.
      Volumetric changes in rats treated with ECS were detected. CONCLUSIONS: Our
      results show that ECS-treatment affects the proliferation of glial cells even in
      the presence of elevated levels of glucocorticoids. This result adds to an
      increasing number of studies suggesting that antidepressant treatment can
      counteract degenerative processes associated with major depression.

PMID- 16431220
TI  - Upregulation of A2A adenosine receptors in platelets from patients affected by
      bipolar disorders under treatment with typical antipsychotics.
AB  - Antipsychotic drugs, potent dopamine receptor antagonists, are commonly used in
      the treatment of psychotic and affective illness. The discovery of antagonistic
      interactions between A2A adenosine receptors (ARs) and D2 dopamine receptors
      (DRs) in the central nervous system suggests that the adenosine system may be
      involved in the pathogenesis of psychiatric and neurological disorders. In the
      present study, we demonstrated for the first time that human platelets co-express
      A2A ARs and D2 DRs assembled into an heteromeric complexes. We also investigated
      the effects of chronic treatment with either typical or atypical antipsychotics
      on A2A AR binding parameters and receptors responsiveness in human platelets from
      patients affected by bipolar disorder. Chronic administration of typical
      antipsychotics induced a significant upregulation of A2A AR binding sites. Since
      no effects on A2A AR were obtained following "in vitro" platelet treatment with a
      typical antipsychotic (haloperidol), we could exclude a direct effect of the drug
      on A2A AR at the peripheral level. Moreover, typical antipsychotics induced a
      significant increase in the agonist potency to mediate A2A AR-G protein coupling.
      On the contrary, chronic treatment with atypical antipsychotics did not induce
      any significant alterations in A2A AR equilibrium binding parameters and receptor
      responsiveness suggesting that typical but not atypical antipsychotic drugs
      induced a selective modification of A2A AR binding parameters in human platelets.
      These results are in accordance with the literature data describing the selective
      A2A AR upregulation induced by typical antipsychotics in human striatum
      suggesting platelets as a peripheral model of the interactions between adenosine
      and dopamine system occurring in the central nervous system.

PMID- 16431221
TI  - Injuries missed by limited computed tomographic imaging of patients with cervical
      spine injuries.
AB  - STUDY OBJECTIVE: It has been prominently suggested that computed tomographic (CT)
      imaging is unnecessary in evaluating patients who have one of a number of
      specific index cervical spine injuries identified on plain radiographs. We seek
      to evaluate this recommendation by examining how frequently patients with these
      index cervical spine injuries have additional secondary injuries that are missed
      on plain radiography. METHODS: We identified all patients in the National
      Emergency X-Radiography Utilization Study (NEXUS) cervical spine data set who had
      an index cervical spine injury identified by plain radiography. We reviewed all
      radiographic studies done on each of these patients, including CT, to determine
      whether any patient sustained additional cervical spine injuries not visualized
      on plain radiographs. RESULTS: Of 818 patients with cervical spine injuries in
      NEXUS, 224 had one of these index cervical spine injuries diagnosed on plain film
      radiography. Eighty-one of these 224 patients (36.2%; 95% confidence interval
      [CI] 29.9% to 42.8%) had at least 1 secondary injury that was not identified on
      plain radiography. A noncontiguous spinal injury was found in 22 of these 81
      patients (27.2%; 95% CI 17.9% to 38.2%) with multiple cervical spine injuries.
      CONCLUSION: More than a third of patients who had one of the index cervical spine
      injuries sustained a secondary injury that was not diagnosed by plain
      radiography, and approximately one fourth of the patients with multiple cervical
      spine injuries have a noncontiguous spinal injury. Guidelines about the necessity
      for CT scanning in such patients should be reconsidered.

PMID- 16431222
TI  - Images in emergency medicine. Orbital cellulites with subperiosteal abscess.

PMID- 16431224
TI  - Images in emergency medicine. No fracture but a foreign body was revealed.

PMID- 16431223
TI  - Clinical decision rules for secondary trauma triage: predictors of emergency
      operative management.
AB  - STUDY OBJECTIVE: Most injured patients taken by ambulance to hospital emergency
      departments do not require emergency surgery, yet most US trauma centers require
      a surgeon to be present on their arrival. If a clinical decision rule could be
      developed to accurately identify which injured patients require emergency
      operative intervention, then such "secondary triage" criteria could permit a
      trauma center to more efficiently use their surgeons' time. METHODS: We analyzed
      7.5 years of data (8,289 consecutive trauma activations) in our prospectively
      maintained Level I trauma center registry. We used classification and regression
      tree analyses to generate clinical decision rules using standard out-of-hospital
      variables to identify emergency operative intervention (within 1 hour) by a
      general surgeon (for adults) or a pediatric surgeon (if < or =14 years). RESULTS:
      Emergency operative intervention occurred in 3.0% of adults and 0.35% of
      children. For adults, summoning a surgeon for any one of 3 criteria (penetrating
      mechanism, systolic blood pressure <96 mm Hg, pulse rate >104 beats/min) could
      reduce surgeon calls by 51.2% while failing to identify emergency operative
      intervention in only 0.08% (rule sensitivity 97.2% and specificity 48.6%). For
      children, no rule at all (ie, never automatically summoning a surgeon) would fail
      to identify emergency operative intervention in only 0.35% of patients, and use
      of a single criterion (penetrating mechanism) would reduce surgeon calls by 96.2%
      while failing to identify emergency operative intervention in only 0.09% (rule
      sensitivity 75.0% and specificity 96.5%). CONCLUSION: We have derived simple
      decision rules for trauma centers that, if validated, could substantially reduce
      the need for routine surgeon presence on trauma patient arrival. These rules
      demonstrate low false-negative rates.

PMID- 16431225
TI  - Ultrasonography in community emergency departments in the United States: access
      to ultrasonography performed by consultants and status of emergency physician
      performed ultrasonography.
AB  - STUDY OBJECTIVE: Nearly all emergency medicine residency programs provide some
      training in emergency physician-performed ultrasonography, but the extent of
      emergency physician-performed ultrasonography in community emergency departments
      (EDs) is not known. We seek to determine the state of ultrasonography in
      community EDs in terms of access to ultrasonography by other specialists and
      performance of ultrasonography by emergency physicians. METHODS: A 6-page survey
      that addressed access to ultrasonography performed by other specialists and
      emergency physician-performed ultrasonography was designed and pilot tested. A
      list of all US ED directors was obtained from the American College of Emergency
      Physicians. Twelve hundred of 5264 EDs were randomly selected to receive the
      anonymous survey, with responses tracked by separate postcard. There were 3
      mailings from Fall 2003 to Spring 2004. RESULTS: Overall response rate was 61%
      (684/1130). Respondents who self-reported as being academic with emergency
      medicine residents were excluded from further analysis (n=35). A sensitivity
      analysis (reported in parentheses) was performed on the key outcome question to
      adjust for response bias. As reported by ED directors, ultrasonography was
      available in the ED for use by emergency physicians at all times in 19% of EDs
      (12% to 28%), with an additional 15% (9% to 21%) reporting a machine available
      for use by emergency physicians in some capacity and 66% (51% to 80%) reporting
      that there was no access to a machine for emergency physician use. ED directors
      reported being requested or required to limit ultrasonography orders performed by
      radiology in 41% of EDs, with less timely access to radiology-performed
      ultrasonography in off hours. Of EDs with emergency physician-performed
      ultrasonography, the most common applications were Focused Assessment with
      Sonography for Trauma (FAST) examination (85%), code situation (72%), and check
      for pericardial effusion (67%). Of physicians performing ultrasonography, 16%
      stated they were currently requesting reimbursement (billing). The primary reason
      cited for not implementing emergency physician-performed ultrasonography was lack
      of emergency physician training. For the statement "emergency medicine residents
      now starting residency should be trained to perform and interpret focused bedside
      ultrasonography," 84% of ED directors agreed, 14% were neutral, and less than 2%
      disagreed. CONCLUSION: Community ED directors continue to report barriers to
      obtaining ultrasonography from consultants, especially in off hours. Nineteen
      percent of community ED directors report having a machine available for emergency
      physician use at all times; however, two thirds of EDs report no access to
      ultrasonography for emergency physician use. A majority of community ED directors
      support residency training in emergency physician-performed ultrasonography.

PMID- 16431226
TI  - Presentation and management of common post-weight loss surgery problems in the
      emergency department.
AB  - Morbid obesity is an epidemic in this country. An increasing number of patients
      are undergoing weight loss surgery in an effort to combat the negative physical
      and psychological impact of morbid obesity. Fueling the increasing interest in
      surgical treatment of morbid obesity has been the development of new laparoscopic
      techniques. There are several surgical approaches to morbid obesity, and each has
      its own unique set of risks and potential complications. As more patients have
      weight loss surgery, clinicians working in the emergency department will
      frequently encounter complications of these procedures. To ensure timely
      diagnosis and optimal care, clinicians should be familiar with the standard
      weight loss approaches and the potential complications of these interventions.

PMID- 16431228
TI  - A case of glaucomatocyclitic crisis in the emergency department.
AB  - Glaucomatocyclitic crisis is caused by an idiopathic inflammatory process of the
      trabecular meshwork, causing a decrease in aqueous outflow. This decrease causes
      the cyclitis-associated ocular hypertension. There is rarely any pain or other
      findings typically associated with glaucoma. Thus, the diagnosis is easily
      missed. Patients may present with nonspecific symptoms such as blurry vision or
      periorbital discomfort. Examination typically reveals a noninjected, slightly
      mydriatic eye. Slit-lamp examination may reveal fewer-than-expected inflammatory
      cells in the anterior chamber, with only occasional small nonpigmented keratic
      precipitates on the corneal epithelium. The intraocular pressure is typically
      increased (30 to 70 mm Hg), despite an open angle. Therapy is aimed at
      controlling the increased intraocular pressure with the use of topical
      imidazolines, beta-blockers, and carbonic anhydrase inhibitors. Complications
      related to prolonged and recurrent attacks of increased intraocular pressure may
      result in damage to the optic nerve head and visual field compromise.

PMID- 16431230
TI  - Early detection of illness associated with poisonings of public health
      significance.
AB  - Since September 11, 2001, concern about potential terrorist attacks has increased
      in the United States. To reduce morbidity and mortality from outbreaks of illness
      from the intentional release of chemical agents, we examine data from the Toxic
      Exposure Surveillance System (TESS). TESS, a national system for timely
      collection of reports from US poison control centers, can facilitate early
      recognition of outbreaks of illness from chemical exposures. TESS data can serve
      as proxy markers for a diagnosis and may provide early alerts to potential
      outbreaks of covert events. We use 3 categories of information from TESS to
      detect potential outbreaks, including call volume, clinical effect, and substance
      specific data. Analysis of the data identifies aberrations by comparing the
      observed number of events with a threshold based on historical data. Using TESS,
      we have identified several events of potential public health significance,
      including an arsenic poisoning at a local church gathering in Maine, the TOPOFF 2
      national preparedness exercise, and contaminated food and water during the
      northeastern US blackout. Integration of poison control centers into the public
      health network will enhance the detection and response to emerging chemical
      threats. Traditionally, emergency physicians and other health care providers have
      used poison control centers for management information; their reporting to these
      centers is crucial in poisoning surveillance efforts.

PMID- 16431231
TI  - Trends in gamma-hydroxybutyrate (GHB) and related drug intoxication: 1999 to
      2003.
AB  - STUDY OBJECTIVE: To analyze changes in gamma-hydroxybutyrate (GHB) case
      reporting, we review GHB or congener drug cases reported to the California Poison
      Control System, comparing these to other data sets. METHODS: We identified cases
      from the California Poison Control System computerized database using
      standardized codes and key terms for GHB and congener drugs ("gamma
      butyrolactone," "1,4-butanediol," "gamma valerolactone"). We noted California
      Poison Control System date, caller and exposure site, patient age and sex,
      reported coingestions, and outcomes. We compared California Poison Control System
      data to case incidence from American Association of Poison Control Centers and
      Drug Abuse Warning Network data and drug use prevalence from National Institute
      for Drug Abuse survey data. RESULTS: A total of 1,331 patients were included over
      the 5-year period (1999-2003). California Poison Control System-reported GHB
      exposures decreased by 76% from baseline (n=426) to the final study year (n=101).
      The absolute decrease was present across all case types, although there was a
      significant proportional decrease in routine drug abuse cases and an increase in
      malicious events, including GHB-facilitated sexual assault (P=.002). American
      Association of Poison Control Centers data showed a similar decrease from 2001 to
      2003. Drug Abuse Warning Network incidence flattened from 2001 to 2002 and
      decreased sharply in 2003. National Institute for Drug Abuse survey time trends
      were inconsistent across age groups. CONCLUSION: Based on the precipitous
      decrease in California Poison Control System case incidence for GHB during 5
      years, the parallel trend in American Association of Poison Control Centers data,
      and a more recent decrease in Drug Abuse Warning Network cases, a true decrease
      in case incidence is likely. This could be due to decreased abuse rates or
      because fewer abusers seek emergency medical care. Case reporting may account for
      part of the decrease in the incidence of poison center contacts involving GHB.

PMID- 16431232
TI  - Resuscitative treatments on 1,4-butanediol mortality in mice.
AB  - STUDY OBJECTIVE: Recent reports on fatalities associated with overdoses from 1,4
      butanediol (1,4-BD), a precursor of the drug of abuse gamma-hydroxybutyric acid
      (GHB), pose the need for investigations focusing on possible pharmacologic
      remedies. Accordingly, the present study investigates whether 4-methylpyrazole (4
      MP; also termed fomepizole and Antizol), an inhibitor of alcohol dehydrogenase
      (the enzyme involved in the first step of the conversion of 1,4-BD into GHB), and
      the gamma-aminobutyric acid B (GABAB) receptor antagonist (2S)(+)-5,5-dimethyl-2
      morpholineacetic acid (SCH 50911), provides protection against 1,4-BD-induced
      mortality in CD1 mice. METHODS: Two sets of experiments were conducted with
      mortality as the outcome measure. In all experiments, mice were initially treated
      with a lethal dose of 1,4-BD (3 g/kg, intragastric [i.g.]). In the first set of
      experiments (dose-response curves), once mice had displayed clear signs of 1,4-BD
      intoxication, animals were randomly allocated in separate groups (n=10) and
      treated acutely with either 4-MP (vehicle, 3, 10, 30, and 100 mg/kg,
      intraperitoneal [i.p.]) or SCH 50911 (vehicle, 75, 150, and 300 mg/kg, i.p.).
      Mortality was recorded every hour for the first 9 hours and 12, 18, and 24 hours
      after 1,4-BD injection. In the second set of experiments (time course), mice were
      randomly allocated in separate groups (n=10). A single dose of either 4-MP (30
      mg/kg, i.p.) or SCH 50911 (150 mg/kg, i.p.) was administered 15, 30, 60, 90, or
      120 minutes after administration of 3 g/kg 1,4-BD (i.g.). Again, mortality was
      recorded every hour for the first 9 hours and 12, 18, and 24 hours after 1,4-BD
      injection. RESULTS: In the dose-response experiments, the acute administration of
      4-MP and SCH 50911 exerted a dose-dependent resuscitative effect in mice acutely
      intoxicated by 3 g/kg 1,4-BD. Specifically, 30 and 100 mg/kg 4-MP and 150 mg/kg
      SCH 50911 protected all treated mice against 1,4-BD-induced mortality.
      Conversely, all mice treated with 4-MP- and SCH 50911-vehicle died. In the time
      course experiments, protection induced by 30 mg/kg 4-MP was complete when
      administered up to 90 minutes after 1,4-BD injection. Vice versa, the complete
      protection induced by 150 mg/kg SCH 50911 progressively diminished as the time
      between 1,4-BD and SCH 50911 administration was increased from 15 to 120 minutes.
      CONCLUSION: These results indicate that both 4-MP and SCH 50911 protected against
      mortality induced by 1,4-BD. Further, these results suggest that 1,4-BD-induced
      mortality in mice is a result of conversion of 1,4-BD into GHB and GHB-induced
      activation of the GABAB receptor. Because both 4-MP and GABAB receptor
      antagonists are available for human use, clinical studies on their ability to
      reverse the consequences of 1,4-BD and GHB intoxication, including fatal events,
      might be considered.

PMID- 16431234
TI  - Intimate partner violence: steps for future generations.

PMID- 16431235
TI  - National Highway Traffic Safety Administration (NHTSA) notes. Evaluation of the
      repeal of the all-rider motorcycle helmet law in Florida.

PMID- 16431233
TI  - Missed opportunities: emergency department visits by police-identified victims of
      intimate partner violence.
AB  - STUDY OBJECTIVE: We examine all emergency department (ED) utilization by police
      identified women victims of intimate partner violence as part of an intimate
      partner violence ED surveillance study to determine the frequency and
      characteristics of visits and the extent of intimate partner violence screening
      and identification by ED staff. METHODS: We conducted a retrospective
      observational case series reviewing countywide EDs visits, 1999 to 2001, for
      women victims in the 2000 prosecutor's intimate partner violence database.
      Stratifying visits by whether the woman presented with an injury, we assessed
      documentation of intimate partner violence screening and identification and
      mental health and substance abuse in the medical records. RESULTS: Of 964 female
      intimate partner violence victims in the 2000 prosecutor's intimate partner
      violence database, 616 (63.9 %) received care in at least 1 ED in the year of the
      index assault. During the 3-year study period, 788 (81.7%) victims generated a
      total of 4,456 ED visits. Intimate partner violence screening was documented in
      1,349 (30.3%) of the 4,456 visits but resulted in only 259 (5.8%) positive
      screens. However, because they use the ED so frequently, 23.0% of individual
      intimate partner violence victims were eventually identified. The median number
      of visits for victim ED users was 4 (range 1 to 71), and visits were just as
      likely to occur before the known intimate partner violence incident as after,
      although ED visits tended to peak in the month of the incident. Injury-related
      visits were 50% more likely to have documented IPV screening, however, most
      visits (71.2%) by IPV victims were for noninjury-related complaints. CONCLUSION:
      Police-identified intimate partner violence victims utilize emergency care at
      extremely high rates, usually without identification or referral to intimate
      partner violence resources.

PMID- 16431236
TI  - The perils of vinegar and the Heimlich maneuver.

PMID- 16431237
TI  - Images in emergency medicine. Subarachnoid space pneumocephalus.

PMID- 16431238
TI  - Images in emergency medicine. Fracture of left clavicle and left posterior rib
      due to birth trauma.

PMID- 16431240
TI  - Evaluation of brief intervention.

PMID- 16431241
TI  - Self-inflicted death during interfacility transfer.

PMID- 16431242
TI  - Questions regarding BNP assays.

PMID- 16431246
TI  - Glomerular and tubular basement membrane calcinosis: case report and literature
      review.
AB  - Nephrocalcinosis most commonly manifests as renal calculi or deposition within
      the tubulointerstitial compartment. Conversely, calcium deposition within
      glomeruli is extremely rare. We present the case of a 50-year-old man with
      multiple medical problems, including hepatitis C, diabetes, hypertension,
      proteinuria, and chronic renal failure. Renal biopsy showed impressive calcium
      deposits along glomerular basement membranes and tubular basement membranes,
      within intracellular organelles, and in the interstitium in the setting of a
      normal serum calcium level. Seven months after biopsy, the patient is on
      hemodialysis therapy. Although serological and medical examination failed to show
      a treatable cause for this patient's glomerular calcinosis, individual case
      reports in the literature have described resolution of calcinosis-associated
      nephrotic syndrome with treatment of the primary cause of hypercalcemia.

PMID- 16431247
TI  - Complement factor H-associated atypical hemolytic uremic syndrome in monozygotic
      twins: concordant presentation, discordant response to treatment.
AB  - Hemolytic uremic syndrome not associated with diarrhea (diarrhea negative,
      atypical) is less common than the diarrhea-positive typical form, but frequently
      results in end-stage renal failure. Although there are anecdotal cases of
      successful treatment with fresh frozen plasma alone, the value of this treatment
      compared with plasma exchange (PE) is difficult to assess. We describe
      monozygotic female twins who presented at 5 years of age with factor H-related
      (c.3572 > T; Ser1191Leu) atypical hemolytic uremic syndrome within months of each
      other. In the first twin to present, 10 sessions of PE with fresh frozen plasma
      replacement (40 mL/kg) resulted in resolution of hemolysis and improvement in
      plasma creatinine level (1.9 to 1.5 mg/dL [166 to 137 micromol/L]). Subsequently,
      17 infusions of fresh frozen plasma were administered during a 4-month period for
      recurrent thrombocytopenia. However, within 4 months, plasma creatinine level
      increased to 5.1 mg/dL (450 micromol/L), necessitating peritoneal dialysis. When
      the second twin presented with the same disease, an extended PE regimen was
      instituted. After 10 daily sessions, PE was continued once every 2 weeks. Two
      recurrences were treated successfully with daily PE for 7 days. After 44 months
      of follow-up, kidney function is normal (plasma creatinine, 0.6 mg/dL [53
      micromol/L]; creatinine clearance, 119 mL/min/1.73 m2 [1.98 mL/s/1.73 m2]) on
      maintenance PE therapy. In conclusion, the response to treatment of these
      monozygotic twins suggests that long-term PE may have benefits over plasma
      infusion alone.

PMID- 16431248
TI  - Ethyl mercury poisoning during a protein A immunoadsorption treatment.
AB  - We describe the case of a 38-year-old woman with Guillain-Barre syndrome who was
      accidentally intoxicated with thimerosal, a column disinfectant containing ethyl
      mercury, during a protein A immunoadsorption treatment. The 1-time overdose
      caused by an equipment handling error led to a maximum blood serum mercury level
      of 2,250 microg/L, thus exceeding the normal blood reference range by a factor of
      approximately 200. Although the patient did not show short-or long-term clinical
      signs of mercury intoxication, she was treated with chelation therapy, and we
      replaced thimerosal with a commercially available mercury-free disinfectant,
      suggesting that thimerosal is no longer indicated for preservation of protein A
      columns.

PMID- 16431250
TI  - C-reactive protein: a family of proteins to regulate cardiovascular function.
AB  - Based on a multitude of clinical studies, C-reactive protein (CRP) has emerged as
      a risk marker for the development of cardiovascular disease, leading to recently
      published recommendations for screening the general population for plasma CRP
      level as a predictor for future cardiovascular events. However, uncertainties
      exist in how to apply these recommendations to populations with very high serum
      CRP levels and a high prevalence of cardiovascular disease, such as patients with
      end-stage renal disease. Furthermore, in vitro results are conflicting concerning
      the role of CRP in the vessel wall. Although many data are in favor of a
      proinflammatory effect of CRP, evidence is accumulating that CRP also exerts anti
      inflammatory actions, mainly in neutrophils and platelets. Many of the apparently
      contradictory actions of CRP may be attributed to method issues, but, of
      interest, also may be explained by the existence of 2 distinct conformations of
      CRP, the native pentamer (nCRP) and modified CRP (mCRP) forms. nCRP is the
      classical acute-phase reactant detected in serum, whereas mCRP represents a
      predominantly tissue-bound form. It is detected immunohistochemically, mainly in
      and around endothelial and vascular smooth muscle cells. Although mCRP activates
      endothelial cells and neutrophils, induces neutrophil adhesion to the
      endothelium, and delays apoptosis of neutrophils in vitro, these effects were
      absent using nCRP. Clearly defined CRP conformers thus may provide a tool for how
      to reconcile the reported proinflammatory and anti-inflammatory properties of
      CRP. There is good evidence to believe that CRP is more than just a "bad guy,"
      and further experiments are needed to determine how these 2 configurations
      contribute to atherogenesis, development of cardiovascular disease, and acute
      coronary events.

PMID- 16431249
TI  - Impact of lipoprotein glomerulopathy on the relationship between lipids and renal
      diseases.
AB  - Lipoprotein glomerulopathy (LPG) is a unique entity of renal lipidosis
      characterized by peculiar histopathologic characteristics of lipoprotein thrombi
      and an abnormal plasma lipoprotein profile resembling type III
      hyperlipoproteinemia, with a marked increase in serum apolipoprotein E (apoE)
      concentrations. At present, 65 cases have been reported worldwide, although most
      patients are found in Japan and east Asian countries. Recently, we identified 4
      types of novel apoE mutations associated with LPG. In particular, a mutation
      designated apoE Sendai, in which arginine 145 is substituted with proline, occurs
      in the majority of Japanese patients. The virus-mediated transduction of apoE
      Sendai resulting in the development of LPG in apoE-deficient mice confirms the
      etiologic role of apoE mutation in LPG. Conversely, experimental graft-versus
      host disease induced in Fc receptor gamma-chain-deficient mice showed LPG-like
      lesions in glomeruli without apoE mutations. Considered together, we believe that
      intrinsic factors in the kidney also contribute to the induction of LPG. Today,
      apoE and related lipid abnormalities are reported to have an important role in
      the development of various renal diseases, eg, diabetic nephropathy and
      immunoglobulin A nephropathy. In this article, we review clinical and
      histopathologic features of LPG, describe the etiologic role of apoE variants and
      intrinsic renal factors, and discuss the impact of LPG on mechanisms of other
      renal diseases.

PMID- 16431251
TI  - Gender and elevated albumin excretion in the Diabetes Control and Complications
      Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC)
      cohort: role of central obesity.
AB  - BACKGROUND: Microalbuminuria (MA), a predictor of cardiovascular disease in
      subjects without diabetes and with type 2 diabetes, is more common in men than
      women in some studies. MA has been linked to central obesity-related traits,
      including increased waist-hip ratio (WHR), suggesting visceral adiposity might
      contribute to elevated albumin excretion rate (AER). These relationships have
      been examined less thoroughly in patients with type 1 diabetes. METHODS: We
      examined the Diabetes Control and Complications Trial (DCCT)/Epidemiology of
      Diabetes Interventions and Complications database obtained 4 years after the end
      of the DCCT to determine whether sex was related to AER in patients with type 1
      diabetes and how WHR, a surrogate for visceral adiposity, affected the sex-MA
      relationship. We fitted models with ln(AER) as the response, adjusted for age,
      hemoglobin A1c level, smoking status, diabetes duration, and blood pressure, plus
      WHR, body mass index (BMI), or sex, alone or in combination. RESULTS: Men had
      greater AERs. WHR was associated with AER, whereas neither sex nor BMI alone was
      associated with AER when adjusted for WHR. For women, but not men, AER was
      associated with waist circumference. CONCLUSION: Sex is associated with AER in
      patients with type 1 diabetes, a relationship accounted for by WHR, consistent
      with a role for visceral adiposity in this process. Whether this observation is
      caused by a direct effect of sex hormones on the kidney and WHR or the effect of
      sex hormones on body fat distribution leading to differences in AER remains to be
      determined.

PMID- 16431252
TI  - A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent
      versus synthetic adrenocorticotropic hormone in idiopathic membranous
      nephropathy.
AB  - BACKGROUND: We conducted a pilot trial to compare the effectiveness and safety of
      2 different treatments in patients with membranous nephropathy and nephrotic
      syndrome. METHODS: To validate the hypothesis that the 2 treatments were
      equivalent, patients with biopsy-proven membranous nephropathy and nephrotic
      syndrome were randomly assigned to methylprednisolone alternated with a cytotoxic
      drug every other month for 6 months (group A) or to intramuscular synthetic
      adrenocorticotropic hormone administered twice a week for 1 year (group B).
      RESULTS: The primary outcome measure is cumulative number of remissions as a
      first event. Fifteen of 16 patients in group A and 14 of 16 patients in group B
      entered complete or partial remission as a first event. After a median follow-up
      of 24 months (interquartile range, 15 to 25 months), there were 4 complete
      remissions and 8 partial remissions in group A versus 8 complete remissions and 6
      partial remissions in group B. Median proteinuria decreased from protein of 5.1
      g/d (interquartile range, 4.0 to 7.3 g/d) to 2.1 g/d (interquartile range, 0.4 to
      3.8 g/d; P = 0.004) in group A and 6.0 g/d (interquartile range, 4.4 to 8.5 g/d)
      to 0.3 g/d (interquartile range, 0.2 to 1.9 g/d; P = 0.049) in group B. Two
      patients from each group interrupted treatment because of side effects or
      inefficacy. CONCLUSION: Most nephrotic patients with membranous nephropathy
      responded to either treatment. Proteinuria was significantly decreased with both
      methylprednisolone and cytotoxic agents or prolonged administration of synthetic
      adrenocorticotropic hormone, without significant differences between these 2
      therapies.

PMID- 16431253
TI  - Silent cerebral white matter lesions and their relationship with vascular risk
      factors in middle-aged predialysis patients with CKD.
AB  - BACKGROUND: Silent cerebral white matter lesions are observed on magnetic
      resonance imaging (MRI) scans in elderly people, and they are related to vascular
      risk factors, particularly hypertension. No data on the prevalence and risk
      factors of white matter lesions in patients with chronic kidney disease (CKD) are
      available. The aim is to analyze the prevalence of white matter lesions and their
      determinants in this population. METHODS: We studied 52 patients without diabetes
      with CKD (stage 3 or 4) aged 30 to 60 years (average, 49 years) and a group of 32
      normotensive control subjects. MRI studies were performed and subcortical and
      periventricular white matter lesions were evaluated by using semiquantitative
      measures. Patients were classified into 2 groups depending on the presence or
      absence of white matter lesions. Echocardiographic studies and measures of
      markers of systemic inflammation (C-reactive protein and interleukin 6) also were
      performed. RESULTS: White matter lesions were more prevalent in patients with CKD
      than controls (33% versus 6%; P = 0.008). Patients with CKD who had white matter
      lesions were older; had a greater history of cardiovascular disease and vascular
      nephropathy as a primary cause of renal disease and greater levels of systolic
      blood pressure, pulse pressure, left ventricular mass index, and C-reactive
      protein; and were administered more antihypertensive drugs than patients with CKD
      without white matter lesions. Stage and duration of CKD were not related to the
      presence of white matter lesions. After adjusting for several factors, only
      vascular nephropathy (odds ratio, 15.6; 95% confidence interval, 1.27 to 191.54;
      P = 0.03) independently predicted an increased risk for white matter lesions.
      CONCLUSION: One third of middle-aged patients with CKD have silent cerebral white
      matter lesions. Vascular nephropathy seems to be the most important factor
      related to the presence of these lesions, suggesting that white matter lesions
      reflect ischemic brain damage caused by generalized vascular damage.

PMID- 16431254
TI  - Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic
      renal disease.
AB  - BACKGROUND: Hypogonadism and anemia are common comorbid conditions in dialysis
      patients. Testosterone replacement may improve such clinical parameters as
      anemia, sarcopenia, and low libido. Additionally, by increasing hemoglobin
      levels, testosterone replacement may allow for a dose reduction in recombinant
      human erythropoietin (rHuEPO), thereby reducing cost. METHODS: This phase IV,
      single-center, placebo-controlled, double-blind study assessed the effect of
      transdermal testosterone on serum testosterone levels, rHuEPO dose required to
      maintain hemoglobin level, bone mineral content, lean body mass and fat content,
      cholesterol level, sexual function, and mood. Forty hypogonadal male hemodialysis
      patients who were administered rHuEPO were randomly assigned to 100 mg of topical
      1% testosterone gel (Testim; Auxilium Pharmaceuticals, Norristown, PA) or
      placebo, applied daily for 6 months. RESULTS: Forty men with a mean age of 56
      years and baseline serum testosterone level less than 300 ng/dL (< 10.4 nmol/L)
      participated in this trial. In men assigned to administration of transdermal
      testosterone, there was an increase beyond that in the placebo group in mean
      serum testosterone (77.1 ng/dL [2.7 nmol/L]), dihydrotestosterone (DHT; 0.8
      nmol/L), and estradiol levels (6.3 pg/mL [23.0 pmol/L]) and a decrease in mean
      serum luteinizing hormone levels (-3.1 IU/L). Compared with subjects administered
      placebo, participants on testosterone replacement therapy did not show an
      appreciable change in rHuEPO dose (mean difference adjusted for baseline values,
      12.6 U/kg/wk; P = 0.73), bone mineral density, lean body mass or fat content,
      cholesterol level, sexual function, or mood. CONCLUSION: Daily administration of
      100 mg of topical 1% testosterone gel for 6 months failed to significantly
      increase serum testosterone or DHT levels in hypogonadal men with end-stage renal
      disease. Treatment with transdermal testosterone did not impact on rHuEPO
      requirement or clinical parameters in this small placebo-controlled study.
      Greater serum testosterone levels may be required to show clinical benefit in men
      with end-stage renal disease.

PMID- 16431255
TI  - Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages
      3 and 4 CKD.
AB  - BACKGROUND: The safety and efficacy of paricalcitol injection have been well
      established for the prevention and treatment of secondary hyperparathyroidism
      (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of
      paricalcitol was developed to provide a convenient dosage form for patients with
      stages 3 and 4 CKD. METHODS: Three randomized, placebo-controlled, phase-3 trials
      were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria
      included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2
      (0.25 and 1.00 mL/s/1.73 m2), an average of 2 consecutive intact parathyroid
      hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium
      levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum
      phosphorus levels of 5.2 mg/dL or less (< or = 1.68 mmol/L). Two studies used a
      thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24
      weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The
      primary efficacy end point is 2 consecutive decreases in iPTH levels greater than
      30% from baseline. RESULTS: Two hundred twenty patients participated (n = 107,
      paricalcitol; n = 113, placebo). At least 2 consecutive decreases in iPTH levels
      of 30% or greater from baseline occurred in 91% of paricalcitol versus 13% of
      placebo patients (P < 0.001). Incidences of hypercalcemia, hyperphosphatemia, and
      elevated calcium-phosphorus product levels were not significantly different
      between groups. Similarly, no significant differences in urinary calcium and
      phosphorus excretion or deterioration in kidney function were detected in
      patients administered paricalcitol compared with placebo. CONCLUSION:
      Paricalcitol capsule was well tolerated and effectively decreased iPTH levels
      with minimal or no impact on calcium levels, phosphorus balance, and kidney
      function in patients with stages 3 and 4 CKD.

PMID- 16431256
TI  - Attitudes of Canadian nephrologists toward multidisciplinary team-based CKD
      clinic care.
AB  - BACKGROUND: Although evidence supporting the advantages of multidisciplinary team
      based chronic kidney disease (CKD) care is not well developed, many groups are
      advocating increased availability of this model. METHODS: The research design is
      a mailed survey sent to 523 members of the Canadian and Quebec Societies of
      Nephrology. RESULTS: After excluding 113 respondents who declared themselves to
      be ineligible, the response rate was 54%. Ninety-one percent of nephrologists
      reported that they usually or always use a CKD clinic. Decisions about when to
      perform CKD-related tasks were based mainly on an estimate of glomerular
      filtration rate, rather than time remaining before end-stage renal disease
      (ESRD). The ideal creatinine clearance for referral to a CKD clinic was 30 to 59
      mL/min (0.50 to 0.98 mL/s), but the usual level was 20 to 29 mL/min (0.33 to 0.44
      mL/s). The ideal time for referral was more than 12 months before ESRD. Renal
      replacement therapy discussions were initiated at a creatinine clearance of 20 to
      29 mL/min (57%). Nephrologists supported promotion of home dialysis for suitable
      patients, but not mandating this. Nephrologists did not provide a blunt prognosis
      to patients who did not specifically ask. Late referral based on adequate time
      for ESRD preparation was reported to be 4 to 6 months (27%), 7 to 9 months (26%),
      or 10 to 12 months (30%). Thirty-eight percent said that optimal preparation
      takes 13 months or longer. CONCLUSION: The literature's common definition of less
      than 3 months as a cutoff value between late and early referral is not endorsed.
      Given that multidisciplinary team-based care is widely available in Canada, this
      study might inform other jurisdictions about the merits and problems associated
      with multidisciplinary team-based care and might shape the agenda for future
      empirical research.

PMID- 16431257
TI  - Clinical outcomes and dialysis adequacy in adolescent hemodialysis patients.
AB  - BACKGROUND: The National Kidney Foundation-Kidney Disease Outcomes Quality
      Initiative guidelines recommend that adult hemodialysis (HD) patients receive a
      minimum dialysis dose by single-pooled Kt/V (spKt/V) of 1.2 or greater. There are
      no data to support a minimum spKt/V dose for children on HD therapy. We aim to
      determine the association of spKt/V with mortality and hospitalization in
      adolescents. METHODS: Clinical characteristics of adolescent HD patients aged 12
      to 18 years old included in the 2000/2001 End-Stage Renal Disease Clinical
      Performance Measures Project were linked to US Renal Data System data from
      October 1, 1999, to October 15, 2001. Hospitalization risks after adjustment for
      time on dialysis therapy, access, hemoglobin level, albumin level, and height
      were determined by means of Poisson regression. spKt/V was analyzed by the adult
      target (< versus > or = 1.2) and by intervals. RESULTS: There were 613 patients
      with 477 patient-years of follow-up, during which there were 14 deaths and 185
      hospitalizations covering 1,108 days. After adjustment, patients with an spKt/V
      less than 1.2 had increased hospitalization risk (1.59; 95% confidence interval,
      0.98 to 2.56; P = 0.06) compared with those with an spKt/V of 1.2 or greater.
      Compared with patients with an spKt/V of 1.2 to 1.4, patients with an spKt/V less
      than 1.2 had increased adjusted risk for hospitalization (2.46; 95% confidence
      interval, 1.23 to 4.94; P = 0.01). Increases in spKt/V beyond 1.4 were not
      associated with improved outcomes. CONCLUSION: Applying the current adequacy
      guideline to adolescent HD patients is justified by the increased hospitalization
      risk of those who fail to attain an spKt/V of 1.2 or greater. However, attaining
      an spKt/V in excess of 1.4 was not associated with greater benefit.

PMID- 16431258
TI  - Serum carboxymethyllysine predicts mortality in hemodialysis patients.
AB  - BACKGROUND: Hemodialysis patients show markedly elevated serum levels of advanced
      glycation end products (AGEs). AGEs have been implicated in the pathogenesis of
      vascular damage and are regarded as a class of uremic toxins. However, to date,
      serum AGE level could not be identified as an independent predictor of mortality.
      The aim of the present study is to test whether serum level of the AGE
      carboxymethyllysine (CML) predicts all-cause or cardiovascular mortality in
      hemodialysis patients. METHODS: Serum total CML concentration was measured by
      means of enzyme-linked immunosorbent assay in 154 patients receiving long-term
      hemodialysis. Patients were divided into groups with serum CML levels less and
      greater than the median (23.8 ng/mg protein). All-cause and cardiovascular
      mortality were registered during a follow-up of 51 months. The relationship
      between serum CML level and mortality was tested by using Kaplan-Meier and Cox
      regression analyses. RESULTS: In the group with low serum CML levels, 38% of
      patients died during the follow-up period; 23% had a cardiovascular cause of
      death. However, in the group with high CML levels, 58% died (P < 0.01) and 36%
      had a cardiovascular cause of death (P < 0.05). The following parameters proved
      to be independent risk factors of all-cause mortality: age (hazard ratio, 1.056;
      P < 0.001), preexisting vascular disease (hazard ratio, 2.53; P < 0.05), smoking
      (hazard ratio, 3.03; P < 0.005), high serum CML level (hazard ratio, 1.776; P <
      0.05), and C-reactive protein level (hazard ratio, 1.017; P < 0.001). CONCLUSION:
      The AGE CML may contribute to increased mortality in patients with uremia.

PMID- 16431259
TI  - Poor short-term survival and low use of cardiovascular medications in elderly
      dialysis patients after acute myocardial infarction.
AB  - BACKGROUND: Beta-blockers, statins, angiotensin-converting enzyme (ACE)
      inhibitors, and angiotensin receptor blockers (ARBs) are standard therapies after
      myocardial infarction (MI) in the general population. Their use and association
      with mortality in elderly dialysis patients after MI have not been studied
      sufficiently. METHODS: Claims records from Medicare and Medicaid patients aged 65
      years and older who participated in prescription benefit plans of 2 eastern
      states were used to identify dialysis patients with MI between 1995 and 2003.
      Study outcomes were outpatient use of beta-blockers, statins, and ACE inhibitors
      and/or ARBs within 90 days after MI. We used multivariate logistic regression to
      assess predictors of such use. Multivariate Cox regression was applied to test
      for associations between beta-blocker, statin, and ACE-inhibitor and/or ARB use
      and 1-year mortality. RESULTS: We identified 902 dialysis patients who were
      hospitalized with MI. Of these, 39.5% died within 90 days and 63.6% died within 1
      year after MI. Of 494 patients who were discharged within 21 days or less and
      survived longer than 90 days, 31.0% were administered an ACE inhibitor and/or
      ARB; 19.4%, a statin; and 34.2%, a beta-blocker after discharge. Use of ACE
      inhibitors and/or ARBs was associated with a 30% reduction in 1-year mortality
      (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.50 to 0.98), whereas
      statin (HR, 0.97; 95% CI, 0.65 to 1.45) and beta-blocker use (HR, 1.05; 95% CI,
      0.78 to 1.43) were not. CONCLUSION: Elderly dialysis patients have excessively
      high mortality and low use of standard therapies after MI. Only ACE inhibitors
      and/or ARBs were associated with a reduced risk for death at 1 year in this
      population. Whether the high mortality rate in this population is attributable to
      such low use of preventive cardiovascular medications remains uncertain.

PMID- 16431260
TI  - The course of hepatitis C virus infection in pretransplantation anti-hepatitis C
      virus-negative renal transplant recipients: a retrospective follow-up study.
AB  - BACKGROUND: The aim of this study is to evaluate the natural course of hepatitis
      C virus (HCV) infection in renal transplant recipients infected shortly before or
      after renal transplantation. METHODS: Seventeen renal transplant recipients with
      no detectable antibodies to HCV before renal transplantation either seroconverted
      after transplantation or developed cholestatic syndrome without seroconversion,
      but with HCV RNA positivity. They were followed up for a mean of 7.2 +/- 4.2 (SD)
      years after renal transplantation and underwent consecutive liver biopsies.
      RESULTS: Biochemical abnormalities initially were observed a median of 5.7 months
      (25th, 75th percentiles, 2.4, 13.9) after transplantation. Initial liver biopsies
      showed acute hepatitis in 5 patients and chronic hepatitis in 9 patients, whereas
      3 patients had histological findings of fibrosing cholestatic hepatitis. During a
      median follow-up of 2.0 years (25th, 75th percentiles, 1.3, 4.6), the condition
      of 5 patients, initially with diagnoses of acute hepatitis, deteriorated rapidly,
      with a median fibrosis progression rate of 0.77 (25th, 75th percentiles, 0.56,
      0.86) per year. Six patients with chronic hepatitis progressed with a median
      fibrosis progression rate of 0.35 (25th, 75th percentiles, 0.15, 0.69) per year
      in a median of 3.1 years (25th, 75th percentiles, 2.4, 3.5), whereas the other 3
      patients with chronic hepatitis with elevated cholestatic liver enzyme levels
      developed early fibrosing cholestatic hepatitis (1 patient) or vanishing bile
      duct syndrome (2 patients). Genotype 1 was found in 7 of 9 patients with
      fibrosing cholestatic hepatitis or vanishing bile duct syndrome (78%; P = 0.049).
      Six of 17 patients died a median of 6.1 years (25th, 75th percentiles, 1.5, 7.1)
      posttransplantation; 4 of these 6 patients died of hepatic failure. CONCLUSION:
      HCV infection acquired shortly before or after renal transplantation frequently
      is associated with an adverse clinical outcome, characterized by rapid
      progression of fibrosis, development of cholestatic syndrome, and high mortality
      rate. Acute hepatitis occurring under maximal immunosuppression is of great
      prognostic significance, determining a specific high-risk group.

PMID- 16431261
TI  - The impact of accepting living kidney donors with mild hypertension or
      proteinuria on transplantation rates.
AB  - BACKGROUND: As waiting times for kidney transplantation increase, individuals
      with hypertension or proteinuria may be considered as eligible living donors. We
      set out to determine how frequently donors are excluded because of hypertension
      or proteinuria and to what extent accepting such donors would increase
      transplantation rates. METHODS: Wait lists from 4 Canadian transplantation
      centers were examined for causes of living kidney donor exclusion. Donors with
      hypertension (clinic blood pressure >140/90 mm Hg or requiring antihypertensive
      medication) or proteinuria historically have been excluded at these centers. We
      define potentially acceptable hypertension as a clinic blood pressure less than
      150/100 mm Hg or less than 140/90 mm Hg if administered a single antihypertensive
      medication and define acceptable proteinuria as protein of 0.15 to 0.3 g/d.
      RESULTS: Only 35% (124 of 352 patients) of wait-listed patients had a living
      donor evaluated (n = 180 potential donors). Primary reasons for donor exclusion
      were immunologic: a positive cross-match (32%; n = 59) or blood group type
      incompatibility (22%; n = 40). Hypertension or proteinuria were less common (17%;
      n = 31). Of 31 donors excluded for hypertension or proteinuria, only 13 had
      results in the acceptable range. Acceptance of these donors would have resulted
      in transplantation of 3% (12 of 352 patients) of the wait-list population.
      CONCLUSION: Accepting living donors with mild hypertension and proteinuria will
      lead to a slight increase in transplantation rates. Efforts to improve living
      donor awareness and overcome immunologic barriers to transplantation may have a
      greater impact.

PMID- 16431262
TI  - Racial differences in coping with the need for kidney transplantation and
      willingness to ask for live organ donation.
AB  - BACKGROUND: Disparities in African-American live donor kidney transplantation
      continue to grow. How patients cope with the reality of end-stage renal disease
      and the ensuing need for dialysis or a kidney transplant may directly affect the
      course of their disease, quality of life, and willingness to ask for live kidney
      donation. Racial differences in coping may exist and relate to the willingness to
      ask for live kidney donation. METHODS: The Brief COPE and Living Organ Donor
      Survey instruments were administered prospectively to potential kidney transplant
      recipients. The 14 different coping mechanisms were analyzed by race to look for
      differences. Willingness to ask for live kidney donation was analyzed to look for
      possible correlations with coping mechanisms and possible predictors analyzed by
      means of logistic regression. RESULTS: Three hundred thirty-three potential
      kidney transplant recipients were administered the surveys, with 61% African
      Americans. Racial differences were seen in the following coping mechanisms:
      acceptance, humor, religion, denial, and behavioral disengagement. Although
      racial differences did not exist in overall willingness to ask for donation,
      positive coping strategies were related to increased willingness to ask for
      donation. CONCLUSION: African Americans cope with the need for a kidney
      transplant differently than non-African Americans. Potential African-American
      kidney recipients are more likely to deny the need for a transplant and are less
      accepting of their situation. This may affect their perception of the need for
      transplantation and their persuasiveness in asking for live donations. Transplant
      programs should ensure that counseling and education programs aim to modify
      unrealistic expectations and improve recipient coping skills.

PMID- 16431264
TI  - A proliferative glomerulonephritis secondary to a monoclonal IgA.
AB  - A distinct entity mimicking immune-complex-mediated glomerulonephritis
      characterized by a proliferative glomerulonephritis with monoclonal
      immunoglobulin G (IgG) deposits recently was described. We now report a case of a
      35-year-old woman who presented with sudden onset of edema, proteinuria,
      hematuria, and hypertension. Renal biopsy showed diffuse endocapillary
      proliferation, mesangial cellularity, and amorphous material in the mesangium.
      Immunofluorescence examination showed mesangial and capillary wall staining for
      IgA (2+), C3 (2+), fibrinogen (2+), and lambda (2+). Congo red stain was
      negative. Electron microscopy showed mesangial and subendothelial deposits with a
      paracrystalline lattice-like substructure forming parallel linear arrays.
      Extensive laboratory evaluation showed a small population of monoclonal plasma
      cells with lambda restriction. The present case suggests that monoclonal IgA
      deposits also can cause proliferative glomerulonephritis. However, the presence
      of paracrystalline deposits in association with monoclonal IgA deposits has not
      been described previously.

PMID- 16431263
TI  - Mendelian randomization: a new approach to studying epidemiology in ESRD.
AB  - Associations between environmental exposures and disease in epidemiological
      studies often are confounded and may result in erroneous interpretations. The
      random assortment of genes from parents to offspring at gamete formation-
      Mendelian randomization--is emerging as a useful method for studying the nature
      (causal or not) of environmental exposures. This occurs because the association
      between a disease and a polymorphism that mimics the biological link between a
      given exposure and the same disease is unaffected by the reverse causation that
      may complicate the interpretation of observational studies. Thus, similarly to
      randomized trials, association studies between gene polymorphisms with a well
      established function may be useful for excluding confounding as an explanation
      for a given epidemiological relationship. The rationale behind this concept is
      that transmission of genes occurs in a random way; therefore, offspring have an
      equal chance of inheriting either of the 2 alleles that their parents have at any
      particular locus, a phenomenon independent from environmental factors. This is
      similar to the construct of randomized trials, in which randomization is expected
      to produce similar distributions of measured and unmeasured confounders between
      treated and untreated (control) groups. The equivalence between random assortment
      of alleles and random assignment of interventions in randomized studies is
      particularly useful because it may give a clue for interpreting associations that
      may be produced as both the effect of a gene or result of an environmental
      exposure. Examples are provided about the use of this concept to elucidate
      paradoxical inverse associations in epidemiological studies in the general and
      end-stage renal disease populations.

PMID- 16431265
TI  - Profound pseudohypocalcemia due to gadolinium (Magnevist) contrast in a
      hemodialysis patient.
AB  - We report the first case of profound "pseudohypocalcemia" after the
      administration of the gadolinium-based contrast media dimeglumine gadopentate
      (Magnevist; Schering Diagnostics AG, Berlin, Germany) to a long-standing
      hemodialysis patient. Initial calcium measurements were made by using our routine
      laboratory colorimetric method based on o-Cresolphthalein (Roche Modular-P; Roche
      Diagnostics Ltd, Lewes, Sussex, UK). Because the patient was well, with no signs
      of hypocalcemia, retrospective testing using both another o-Cresolphthalein
      colorimetric method (Roche Integra 800) and measurement of ionized calcium with
      an ion-selective electrode were performed, and confirmed laboratory
      pseudohypocalcemia.

PMID- 16431266
TI  - Transplantation using marginal living donors.

PMID- 16431267
TI  - Study designs in patient-oriented research.

PMID- 16431268
TI  - Subepithelial humps and microthrombi: looking for a mechanism.

PMID- 16431269
TI  - Serum leptin and epoetin sensitivity.

PMID- 16431272
TI  - To reuse or not to reuse: a tale of 2 studies.

PMID- 16431273
TI  - Pseudohyperkalemia in leukemias.

PMID- 16431274
TI  - Isolation, cloning and expression analysis of EcPMA1, a putative plasma membrane
      H+ -ATPase transporter gene from the biotrophic pathogenic fungus Erysiphe
      cichoracearum.
AB  - Little is known at the molecular level about the transporters involved in
      nutrient transfer in the plant/powdery mildew interaction. A PCR-based approach
      was used to identify and isolate a partial-length cDNA coding for an isoform of
      the plasma membrane H+ -ATPase (EcPMA1) in the biotrophic pathogenic fungus
      Erysiphe cichoracearum. Southern analysis suggests that EcPMA1 exists as a single
      copy gene. Sequence analysis indicated a high similarity of EcPMA1 to other
      fungal H+ -ATPases. Expression of EcPMA1 increases in infected Arabidopsis leaves
      as the disease progresses, correlating with the growth of the pathogen.

PMID- 16431275
TI  - The three beta-1,3-glucanases from Acremonium blochii strain C59 appear to be
      encoded by separate genes.
AB  - Three exocellular beta-1,3-glucanases from Acremonium blochii strain C59, BGN3.2,
      BGN3.3 and BGN3.4, were purified. Two, BGN3.2 and BGN3.4 appeared to act as exo
      enzymes against laminarin from Laminaria digitata, while BGN3.3 displayed an endo
      mode of action. The N-terminal amino acid sequence data for BGN3.2 and BGN3.4
      suggested these two enzymes may be encoded by different genes. The gene encoding
      the BGN3.2 glucanase was fully sequenced, and its deduced amino acid sequence was
      similar to those for all other sequenced fungal exo-beta-1,3-glucanases. This
      BGN3.2 gene consists of an uninterrupted ORF of 2349 bp encoding 783 amino acids
      possibly with two cleavage sites for the potential removal of a pre- and pro
      protein, respectively. A DNA fragment encoding a portion of the BGN3.4 gene was
      amplified by PCR, and the nucleotide sequence of this fragment confirmed that
      BGN3.2 and BGN3.4 are encoded by different genes. The internal peptide sequences
      of BGN3.3 were not present in the amino acid sequence deduced from the BGN3.2
      gene, reinforcing the view that BGN3.3 is also genetically different to BGN3.2.
      Genetic differences between multiple forms of fungal beta-1,3-glucanases from a
      single fungus have not been reported previously.

PMID- 16431276
TI  - Diversity and evolution of 5S rRNA gene family organization in Pythium.
AB  - The 5S rRNA gene family organization among 87 species and varieties of Pythium
      was investigated to assess evolutionary stability of the two patterns detected
      and to determine which pattern is likely the ancestral state in the genus.
      Species with filamentous sporangia (Groups A-C according to the ITS phylogenetic
      tree for Pythium) had 5S genes linked to the rDNA repeat that were predominantly
      coded for on the DNA strand opposite to the one with the other rRNA genes
      ('inverted' orientation). A small group of species with contiguous sporangia
      (Group D) is related to Groups A-C but had unlinked 5S genes. The main group of
      species with spherical zoosporangia (Groups E-J) generally had unlinked 5S genes
      in tandem arrays. The six species in Group K, although they also have spherical
      sporangia, had linked genes on the same strand as the other rRNA genes 'non
      inverted' and most of them had pairs of tandem 5S genes. The evolutionary
      stability of 5S sequence organization was compared with the stability of
      morphological characters as interpreted from a phylogeny based on ITS sequence
      analysis. Features of 5S sequence organization were found to be just as
      consistent within groups as were the morphological characters. To determine the
      ancestral type of 5S family organization, a survey of Phytophthora strains was
      conducted to supply an outgroup reference. The most parsimonious interpretation
      of the data in this survey yielded the tentative conclusion that the linked
      condition of the 5S sequences was ancestral.

PMID- 16431277
TI  - Relationship between temperature optima and secreted protease activities of three
      Pythium species and pathogenicity toward plant and animal hosts.
AB  - The in vitro physiological characteristics of three species of Pythium
      (oomycetes) that utilize different food sources were compared with their
      ecological activities: P. insidiosum is a pathogen of mammals (including humans),
      P. graminicola infects the roots of graminaceous hosts, and P. grandisporangium
      is an enigmatic water mold isolated from mangrove leaves and marine algae. P.
      insidiosum and P. graminicola showed peak growth rates at 37 degrees C before
      complete inhibition of growth at 40 degrees C; P. grandisporangium grew fastest
      at 22 degrees C. Differences between the invasive pressures exerted by the hyphae
      of these microorganisms were not considered significant in relation to the
      substrates colonized by these water molds. All three species showed substantial
      secreted protease activity, producing three or more serine proteases with weights
      ranging from 24-38 kDa. Fastest growth rates were supported when collagen was
      supplied as the sole carbon source, and none of the species were able to grow on
      purified plant cell wall polysaccharides. The growth and nutritional
      characteristics of P. graminicola and P. grandisporangium bear little obvious
      relationship to the ecological niches that they inhabit. This highlights the
      caution necessary in extrapolating from laboratory analyses to the natural
      environment, and points to the potential importance of ecological opportunity in
      determining the host range and food source of certain microorganisms.

PMID- 16431278
TI  - Glycine-rich protein genes, which encode a major component of the cuticle, have
      different developmental profiles from other cuticle protein genes in Bombyx mori.
AB  - Three types of GRP (glycine-rich proteins) cDNAs were identified in the EST
      database of Bombyx mori. These came from 21 ESTs in the W3-stage wing disc EST
      library. We named them BmGRP1, BmGRP2 and BmGRP3. BmGRP1 and BmGRP2 had 57%
      identity in deduced amino acid sequences. Expression of all BmGRPs was observed
      in the epidermis at the fourth molting stage, and in the wing at pupation and mid
      pupal stage. It is suggested that BmGRPs contribute to larval, pupal and adult
      cuticles together with other cuticle proteins. Transcripts of BmGRP2 increased
      after 7 days of pupal stage. BmGRP2 is suggested to construct adult trachea in
      the wing. Hormonal response of BmGRPs was compared with that of another group of
      cuticular protein genes, BMWCPs. BmGRPs were induced by a pulse of 20E. Induction
      of BmGRP3 was observed in W1 wing discs in the presence of JHA which was added
      with 20E, whereas that of BMWCP2 was inhibited in the presence of JHA. Induction
      of BmGRPs was observed in the wing discs of V3 and W1 stages, while that of
      BMWCP2 was not observed in the V3 wing discs. These differences between BMWCPs
      and BmGRPs in response to hormones at different developmental stages are
      discussed.

PMID- 16431280
TI  - Substrate specificity of insect trypsins and the role of their subsites in
      catalysis.
AB  - Trypsins have high sequence similarity, although the responses of insect trypsins
      to chemical and natural inhibitors suggest they differ in specificities. Purified
      digestive trypsins from insects of four different orders were assayed with
      internally quenched fluorescent oligopeptides with two different amino acids at
      P1 (Arg/Lys) and 15 amino acid replacements in positions P1', P2', P2, and P3.
      The binding energy (deltaG(s), calculated from Km values) and the activation
      energy (deltaG(T)(double dagger), determined from kcat/Km values) were
      calculated. Dictyoptera, Coleoptera and Diptera trypsins hydrolyze peptides with
      Arg at P1 at least 3 times more efficiently than peptides with Lys at P1, whereas
      Lepidoptera trypsins have no preference between Arg and Lys at that position. The
      hydrophobicities of each subsite were calculated from the efficiency of
      hydrolysis of the different amino acid replacements at that subsite. The results
      suggested that insect trypsin subsites become progressively more hydrophobic
      along evolution. Apparently, this is an adaptation to resist plant protein
      inhibitors, which usually have polar residues at their reactive sites. Results
      also suggested that, at least in lepidopteran trypsins, S3, S2, S1', and S2'
      significantly bind the substrate ground state, whereas in the transition state
      only S1' and S2' do that, supporting aspects of the presently accepted mechanism
      of trypsin catalysis. Homology modeling showed differences among those trypsins
      that may account for the varied kinetic properties.

PMID- 16431279
TI  - An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks.
AB  - Over 8000 expressed sequence tags from six different salivary gland cDNA
      libraries from the tick Ixodes scapularis were analyzed. These libraries derive
      from feeding nymphs infected or not with the Lyme disease agent, Borrelia
      burgdorferi, from unfed adults, and from adults feeding on a rabbit for 6-12 h,
      18-24 h, and 3-4 days. Comparisons of the several libraries led to identification
      of several significantly differentially expressed transcripts. Additionally, over
      500 new predicted protein sequences are described, including several novel gene
      families unique to ticks; no function can be presently ascribed to most of these
      novel families. Among the housekeeping-associated transcripts, we highlight those
      enzymes associated with post translation modification of amino acids,
      particularly those forming sulfotyrosine, hydroxyproline, and carboxyl-glutamic
      acid. Results support the hypothesis that gene duplication, most possibly
      including genome duplications, is a major player in tick evolution.

PMID- 16431281
TI  - Caste-based differences in gene expression in the polyembryonic wasp Copidosoma
      floridanum.
AB  - The polyembryonic parasitoid Copidosoma floridanum produces two larval castes,
      soldiers and reproductives, during development within its host. Soldier larvae
      defend the brood against competitors while reproductive larvae develop into adult
      wasps. As with other caste-forming insects, the distinct morphological and
      behavioral features of soldier and reproductive larvae likely involve
      differential gene expression. In this study we used a bi-directional suppression
      subtractive hybridization (SSH) approach to isolate differentially expressed
      genes from C. floridanum soldier and reproductive larvae. We isolated 230 novel
      expressed sequence tags (ESTs) from the two subtractions (114 soldier/116
      reproductive ESTs). Among these ESTs were sequences with significant similarity
      to genes coding for serine proteinases, proteinase inhibitors, odorant-binding
      and chemosensory proteins, and cuticular proteins. Also, three novel genes were
      isolated that resemble one another in conceptual translation and share the
      cysteine spacing pattern of short scorpion toxins and insect defensins. Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis of 20 ESTs from the two
      libraries indicated that 85% were differentially expressed in one caste or the
      other. We conclude that our SSH strategy was effective in identifying a number of
      genes differentially expressed in soldier and reproductive larvae and that
      several of these genes will be useful in characterizing caste-specific gene
      networks in C. floridanum.

PMID- 16431282
TI  - Characterization of a serine carboxypeptidase in the salivary glands and fat body
      of the orange wheat blossom midge, Sitodiplosis mosellana (Diptera:
      Cecidomyiidae).
AB  - A full-length cDNA encoding a serine carboxypeptidase (designated SmSCP-1) was
      recovered from an ongoing salivary gland EST project of the wheat midge. The
      deduced 461-amino acid sequence had a putative signal sequence at the amino
      terminus, indicating it was a secreted protein. The protein shared homology with
      serine carboxypeptidases from other insects, mammals, plants, and yeasts. SmSCP-1
      mRNA was expressed in all stages of development and detected in salivary gland
      and fat body tissues but not in midgut tissue. Expression analysis and
      quantitative real-time PCR assays in male and female wheat midges and the fat
      body tissue of adult midges revealed that SmSCP-1 was up-regulated nearly four
      fold in the female midges compared to males and nearly two-fold in female fat
      body compared to male fat body. The wheat midge serine carboxypeptidase (SmSCP-1)
      most likely has a dual function. As a secreted digestive enzyme, it could play a
      role in mobilizing host-plant seed reserves for feeding larvae and as expressed
      in fat body could function as an exopeptidase in degradation of vitellogenin
      and/or in post-translational processing of other enzymes.

PMID- 16431283
TI  - An alanine in segment 3 of domain III (IIIS3) of the cockroach sodium channel
      contributes to the low pyrethroid sensitivity of an alternative splice variant.
AB  - In a previous study, we showed that two alternative exons (G1 and G2 encoding
      IIIS3-S4) were involved in the differential sensitivity of two cockroach sodium
      channel splice variants, BgNa(v)1-1 and BgNa(v)2-1 (previously called KD1 and
      KD2), to deltamethrin, a pyrethroid insecticide (Tan, et al., 2002b. Alternative
      splicing of an insect sodium channel gene generates pharmacologically distinct
      sodium channels. J. Neurosci. 22, 5300-5309.). Here, we report the identification
      of an amino acid residue in exon G2 that contributes to the low deltamethrin
      sensitivity of BgNa(v)2-1. Replacement of A1356 in BgNa(v)2-1 with the
      corresponding V1356 in BgNa(v)1-1 enhanced the sensitivity of the BgNa(v)2-1
      channel to deltamethrin by six-fold. Conversely, substitution of V1356 with A1356
      in BgNa(v)1-1 produced a recombinant BgNa(v)1-1 channel that was 5-fold more
      resistant to deltamethrin. These results demonstrate that A1356 contributes to
      the low sensitivity of BgNa(v)2-1 to deltamethrin. A1356V substitution also
      shifted the voltage-dependence of activation by 10 mV in the hyperpolarizing
      direction. Possible mechanisms by which this amino acid change affects the action
      of pyrethroids on the sodium channel are discussed.

PMID- 16431284
TI  - In vivo treatment of mice with heat shock protein, gp 96, improves survival of
      skin grafts with minor and major antigenic disparity.
AB  - Immunization with high doses of heat shock protein, gp 6 given in vivo, has been
      shown to mediate the activation of CD4+ T cell, which in turn suppresses an
      ongoing CD8+ immune response. Here we demonstrate that high doses of gp 6 (HDgp
      6) (100 microg given subcutaneously on days 0 and 7 following skin graft
      transplantation) improve survival of skin grafts with both minor and major
      histocompatibility. First, skin from male C57BL/6 donors was grafted onto female
      C57BL/6 recipients that were subsequently treated with either HDgp 6 or buffer
      and graft survival was monitored. At 64 days post-transplantation, graft
      recipients treated with HDgp 6 showed 56% graft survival compared to 10% in those
      treated with buffer. Further, HDgp 6 down regulates a secondary immune response
      as well. Skin graft obtained from a male C57BL/6 donor was transplanted to a
      female C57BL/6 recipient that had previously rejected a male skin graft.
      Recipients that were treated with HDgp 96 showed a 75% graft survival of the
      secondary graft at 64 days post-transplantation, whereas recipients treated with
      buffer rejected their secondary grafts within 37 days. Finally, the effect of
      HDgp 96 treatment on survival of graft with major histoincompatibility was
      tested. Skin grafts from female BALB/c donors were transplanted to female C57BL/6
      recipients previously treated with either HDgp 96 or buffer. Although all the
      grafts were ultimately rejected, mice treated with HDgp96 showed a delay in the
      rejection as compared with buffer controls. Our findings indicate that HDgp 96
      improves survival of grafts with both minor and major antigenic disparity and
      could lead to developing novel therapies in transplant medicine.

PMID- 16431285
TI  - HLA class I antibody mediated accommodation of endothelial cells via the
      activation of PI3K/cAMP dependent PKA pathway.
AB  - Allografts transplanted across ABO incompatibility or human leucocyte antigen
      (HLA)-sensitization undergoes antibody (Ab) mediated hyperacute rejection.
      Depleting anti-graft Ab from the recipient by plasmapheresis prior to
      transplantation can prevent this Ab-mediated rejection. Under these conditions,
      allografts have been shown to function even when the Ab rebound in the
      recipients. We have developed an in vitro model using human aortic endothelial
      cells (EC) and elucidated the ability of W6/32 HLA class I monoclonal Ab to
      provide signals following binding to MHC class I molecules. Using this model, we
      show that ECs undergo caspase 3-dependent cell death by apoptosis upon exposure
      to saturating concentrations of W6/32 and complement. In contrast, exposure of
      ECs to sub-saturating concentrations of W6/32 conferred resistance towards
      Ab/complement-mediated lysis that has been termed accommodation. Accommodated ECs
      exhibited a significant increase in the expression of anti-apoptotic genes Bcl
      xL, Bcl-2 and Heme Oxygenase-1 and the induction of Phosphatidylinositol 3 kinase
      (PI3K) and cyclic adenosine monophosphate (cAMP) dependent protein kinase A
      activities that facilitate the phosphorylation of Bad at positions Ser(136) and
      Ser(112). In conclusion, exposure of sub-saturating concentrations of HLA class I
      Ab results in the induction of signals downstream that confers resistance to
      endothelial cells against Ab-complement mediated cell death. Together, the
      observations made in this study will provide the basis for delineating the
      molecular mechanisms involved in mediating accommodation and developing
      strategies to induce accommodation in grafts prior to transplantation in highly
      sensitized patients.

PMID- 16431286
TI  - Low dose busulfan facilitates chimerism and tolerance in a murine model.
AB  - T cell depletion, sirolimus and "mega" dose donor specific bone marrow (DSBM)
      infusion promotes stable multilineage chimerism and indefinite survival of skin
      allografts in completely mismatched mice. The purpose of this study is to
      determine whether the addition of low dose busulfan can reduce the amount of DSBM
      required while preserving efficacy. C57BL/6 recipients of BALB/c skin allografts
      were treated with alphaCD4 and alphaCD8 monoclonal antibodies, DSBM, sirolimus
      and various doses of busulfan. The kinetics and phenotype of chimerism and the
      presence of clonal deletion of alloreactive T-cells were defined using flow
      cytometry. In vitro reactivity was determined using mixed lymphocyte culture.
      Second skin grafts confirmed the presence of tolerance. All doses of busulfan
      resulted in engraftment when combined with this regimen using a reduced dose of
      donor marrow. The level, kinetics and character of chimerism observed were dose
      related. Chimerism was associated with indefinite allograft acceptance (>200
      days). Tolerance was documented both in vitro/in vivo and was associated with
      clonal deletion. Addition of a single low dose of busulfan to an established
      tolerance protocol reduced the required DSBM dose by over 80% while still
      promoting comparable levels of donor chimerism and donor-specific tolerance.

PMID- 16431287
TI  - The presence of donor-reactive CD4 T cells in early-phase liver-induced tolerance
      in rats: analysis using donor passenger leukocytes from the recipient.
AB  - In previous studies, we showed that the recipient spleen 12 h after liver
      transplantation included highly immunogenic donor passenger leukocytes (PLs) in
      the non-rejector rat strain combination (Lewis: LEW-->Wistar Furth: WF).
      Furthermore, we noted that giving anti-CD4 mAb to WF recipients at the time of
      liver grafting prolonged the liver damage due to primary rejection reaction,
      suggesting that CD4 T-cell regulation but not the deletional mechanism played a
      dominant role during the induction phase of tolerance in this combination. We
      proposed that in vitro CD4 T-cell response to the donor PLs from the recipient
      lymphoid organ may be observed in the early phase of tolerance induction. We
      initially observed donor-specific acceptance by 10 days after liver
      transplantation from the result of secondary heart transplantation, and showed
      that donor (LEW) PLs in recipient WF spleen 12 h after grafting were able to
      prime cytotoxic CD8 T cells in vivo. We then isolated functional donor PLs from
      the recipient WF spleen and established in vitro proliferation assay. When the
      enriched donor PLs were used as stimulator cells in the proliferation assay, a
      powerful alloimmunostimulatory ability was observed. Moreover, a potent response
      of recipient splenocytes to the PLs was observed on postoperative day 14. From
      these observations, we confirmed that clonal deletion of donor-reactive CD4 T
      cells did not participate in early phase of tolerance induction in this setting.

PMID- 16431288
TI  - Differential origin for endothelial and mesangial cells after transplantation of
      pig fetal renal primordia into rats.
AB  - Xenotransplantation of renal primordia in lieu of human kidney allografts has
      been proposed as a solution for the lack of organ availability. We and others
      have shown that growth and development of pig renal primordia occur post
      transplantation across a highly disparate xenogenic barrier to rat. The origins
      (donor versus host) of endothelial cells (ECs) and mesangial cells (MCs) in
      grafts are incompletely delineated. In the present study, we investigated using
      immunohistochemistry, the origin ECs and MCs of the metanephric xenografts
      originating from embryonic day 28 (E28) pig embryos transplanted into rats. We
      employed species-specific antibodies: anti-rat endothelial cell antigen-1 (RECA
      1) and -CD31 to detect rat- and pig-derived ECs, respectively; and anti-Thy-1 and
      -vimentin to detect rat- and pig-derived MCs, respectively. Both intra- and
      extraglomerular ECs in the xenografts were stained exclusively with rat-specific
      anti-RECA-1 at 5, 7, or 8 weeks post-transplantation, whereas ECs were not
      stained with pig-specific anti-CD31. In contrast, MCs in the xenografts were
      stained predominantly using the pig specific anti-vimentin, although a few
      glomeruli were positive for rat-specific anti-Thy-1. We conclude that the
      predominant origin of ECs post-transplantation of embryonic pig metanephroi into
      rats is the host, whereas MCs originate mainly from the donor.

PMID- 16431289
TI  - Increased urinary excretion of transforming growth factor-beta(1) in renal
      transplant recipients during cytomegalovirus infection.
AB  - AIMS: Cytomegalovirus (CMV) is a suggested risk factor for chronic allograft
      nephropathy, and transforming growth factor-beta (TGF-beta) is a key fibrogenic
      molecule in this process. CMV has been shown to induce the expression of TGF-beta
      and several cytokines. We analyzed the impact of CMV on urinary excretion of TGF
      beta, ICAM-1, TNF-alpha and correlated findings with biopsy histology. MATERIAL:
      Urine samples from 46 renal transplant recipients were available for the study.
      Urine samples were taken when CMV infection was suspected, or for controlling of
      proteinuria or bacteriuria. METHOD: CMV was diagnosed by antigenemia and viral
      cultures. Patients with previous CMV infection were excluded from the analysis.
      Urine samples were analyzed by ELISA-method to detect the levels of TNF-alpha,
      ICAM-1 and TGF-beta(1). Banff '97 criteria were used for scoring of protocol
      biopsies taken 6 months after transplantation. RESULTS: At the time of the urine
      collection, 13/46 patients had CMV infection. Eight patients with no CMV
      infection were used as controls. TGF-beta(1) was significantly increased in the
      CMV group (samples taken mean 137+/-79 days post-transplantation) compared to
      controls (samples 139+/-64 days post-transplantation) (51.1+/-28.0 vs. 13.3+/-6.7
      ng/mmol crea, p<0.001). No differences in the levels of other molecules were
      recorded. In the biopsies, interstitial fibrosis was significantly increased in
      the CMV group compared to controls. CONCLUSIONS: Urinary excretion of TGF-beta(1)
      was increased in patients during CMV infection. This was associated with
      increased fibrosis in the biopsies.

PMID- 16431290
TI  - Effect of IL-18 and sIL2R on aGVHD occurrence after hematopoietic stem cell
      transplantation in some Iranian patients.
AB  - BACKGROUND: Graft-versus-host disease is one of the major complications after
      allogeneic bone marrow transplantation, but it is not easy to anticipate the
      onset. Cytokines released by type 1 T helper cells are thought to play a pivotal
      role in acute graft-versus-host disease aGVHD. The ability to predict the likely
      occurrence of graft-versus-host-disease (GVHD) after Hematopoietic Stem cell
      Transplantation (HSCT) would be extremely valuable. By serially measuring serum
      levels of soluble IL-2 receptor (sIL-2R), IL-18 and following allogeneic HSCT we
      tried to define their effect on aGVHD as a complication of transplantation and
      determine useful markers for aGVHD predictors. SAMPLES AND METHODS: Serum sIL-2R,
      IL-18, levels were measured by sandwich ELISA in 219 sera samples from 39
      patients (with hematological disorders before and after allogeneic HSCT) and 28
      controls. All patients received transplants from HLA-identical siblings. RESULTS:
      23 (58.9%) patients developed aGVHD (I-IV) and serum levels of sIL-2R and IL-18,
      in sera drawn before transplantation, in patients with acute graft-versus-host
      disease (aGVHD(+)), were increased in comparison to patients without acute graft
      versus-host disease (aGVHD(-)) and to a control group and there were no
      significant differences in serum levels of sIL-2R and IL-18 in aGVHD(-) patients
      and controls. Serum level of IL-18, in aGVHD(+) patients, was increased during
      days 3-24 after HSCT, and there was a significant difference according to GVHD
      severity. In majority of patients with acute GVHD (60%), the peak levels of IL-18
      and sIL-2R were achieved on day 10 after HSCT and the rise in sIL-2R and IL-18
      preceded the clinical signs of GVHD (mean day 15 after BMT). The level of IL-18
      in patients with aGVHD strongly correlated with the severity of aGVHD on Day 10
      after HSCT. IL-18 level (before HSCT), in patients who received Busulfan and
      Fludarabin which were used to treat aGVHD, was lower than in patients who
      received Busulfan and Cyclophosphamide. CONCLUSION: Our data concluded that IL-18
      plays an important role in the development of aGVHD and the IL-18 level might be
      an indicator of aGVHD, reflecting the severity of the disease. These findings
      suggest that IL-18 may play an important role in the pathogenesis of aGVHD and
      that measurement of serum IL-18 levels can be a useful indicator of aGVHD.

PMID- 16431291
TI  - Apoptosis of allospecifically activated human helper T cells is blocked by
      calcineurin inhibition.
AB  - BACKGROUND: Classical transplantation immunosuppression relies heavily upon the
      interruption of interleukin-2 (IL-2) signaling by calcineurin inhibition.
      However, recent evidence in murine models suggests that IL-2 is necessary for
      activation-induced cell death (AICD) of allograft-specific lymphocytes. METHODS:
      We examined the apoptotic effects of the calcineurin inhibitor cyclosporine A and
      mTOR inhibitor rapamycin on the apoptotic alterations that occur in
      allospecifically activated human lymphocytes in a one-way mixed lymphocyte
      culture (MLC). RESULTS: Cyclosporine increased caspase-3 activation in MLC, which
      corresponded with a decrease in lymphocyte apoptosis in MLC. Cyclosporine also
      reduced apoptosis in the CD4+ helper T cell subset, while CD8+ cells had similar
      or increased apoptosis when compared to controls. In contrast, rapamycin-treated
      cultures had normal levels of CD4+ T cell apoptosis when compared to control MLC,
      with decreases seen in CD8+ T lymphocytes. CONCLUSIONS: In humans, blockade of IL
      2 receptor signal with rapamycin allows apoptosis of allospecifically activated
      CD4+ lymphocytes to occur, while blockade of IL-2 production with cyclosporine
      results in decreased apoptosis in this T cell subset. As helper T cells are
      integral to the immune response, these results may explain the tolerogenic
      effects of rapamycin.

PMID- 16431292
TI  - Impact of ABCB1 (MDR1) haplotypes on tacrolimus dosing in adult lung transplant
      patients who are CYP3A5 *3/*3 non-expressors.
AB  - BACKGROUND: The influence of ABCB1 (MDR1) polymorphisms on tacrolimus dosing has
      been questioned in previous studies with contradictory findings, possibly due to
      the association between CYP3A5 polymorphisms and tacrolimus dosing. The objective
      of this study was to assess the effect of ABCB1 haplotypes from 3 distinct
      polymorphic sites on the tacrolimus level/dose [L/D] in lung transplant patients
      limited to CYP3A5 *3/*3 non-expressors. METHOD: A total of 91 lung transplant
      patients treated primarily with tacrolimus and prednisone were enrolled, and
      clinical information on drug dosing and blood levels was collected. The [L/D] was
      calculated for patients receiving tacrolimus at 1, 3, 6, 9 and 12 months post
      transplant. ABCB1 polymorphisms at C1236T, G2677T, and C3435T were assessed by
      PCR amplification and DNA sequencing. Haplotypes were estimated by Arlequin
      ver.2.00. Haplotype effects on tacrolimus [L/D] were assessed by two-way ANOVA.
      RESULTS: Of the 10 haplotypes, CGC, TTT and CGT accounted for 44.1%, 40.7% and
      7.6% of the total haplotypes, respectively. The tacrolimus [L/D] value in the CGC
      CGC patients was significantly lower than in patients with CGC-TTT and TTT-TTT
      genotypes at the first month (mean [L/D]=1.45 versus 3.10 and 3.97 ngxmL(-)(1)
      /mg/day), and throughout the first post transplant year. CONCLUSION: This study
      demonstrates that ABCB1 haplotypes derived from three common polymorphisms are
      associated with tacrolimus dosing in lung transplant patients when eliminating
      the confounder CYP3A5 genotype.

PMID- 16431294
TI  - Pneumatosis intestinalis: a rare cause of diarrhea and hematochezia.

PMID- 16431293
TI  - Hyperleptinemia and its relation with peripheral C34(+)CD7(+) stem cells in renal
      transplant recipients.
AB  - OBJECTIVES: Leptin, the Ob gene product, centrally regulates weight control.
      Transplant recipients are exposed to many factors affecting body mass. Leptin has
      been reported to activate the peripheral immune system. In this study, we
      evaluated serum leptin levels and factors contributing to hyperleptinemia; the
      relationship between serum leptin levels and lymphoid stem and mature cells; and
      their role in the rejection process in renal transplant recipients. MATERIALS AND
      METHODS: Sixty-three renal transplant recipients were included in the study.
      Patients were grouped according to serum leptin percentiles as hypoleptinemic
      (n=17), normoleptinemic (n=32), and hyperleptinemic (n=14). We determined serum
      leptin levels by radioimmunoassay and absolute number of CD34(+), CD7(+),
      CD34(+)CD7(+) lymphoid stem cells, CD4(+) and CD8(+) lymphocytes in peripheral
      blood by flow cytometry. RESULTS: The hyperleptinemic patients constituted 22.3%
      of the transplant patient. The mean peripheral blood CD34(+)CD7(+) lymphocyte
      count was significantly higher in hyperleptinemic patients than in normo- or
      hypoleptinemic patients (6.9, 6.1, and 44.3 cells/mm(3), respectively, P<0.05).
      There were no significant differences in the mean CD34(+), CD7(+), CD8(+), and
      CD4(+) lymphocyte count and CD4/CD8 ratio among the groups with respect to serum
      leptin levels. CD34(+)CD7(+) lymphocyte count was positively correlated with
      serum leptin levels (r=0.416, P<0.05). CONCLUSIONS: Hyperleptinemia is not rare
      during the posttransplant period. Our data support the results of previous
      experimental studies that have demonstrated the effect of the leptin hormone on
      lymphoid stem cells. The central and peripheral effects of leptin may differ on
      lymphoid stem cells and a serum threshold level may apply for the central
      effects.

PMID- 16431295
TI  - Unusual endoscopic presentation of Whipple's disease.

PMID- 16431296
TI  - Malignant insulinoma.

PMID- 16431298
TI  - Short bowel syndrome and intestinal failure: consensus definitions and overview.
AB  - Short bowel syndrome (SBS)-associated intestinal failure is a highly disabling
      condition that impairs quality of life and social integration. Although the
      condition is not uniformly fatal, it might lead to serious, life-threatening
      complications. The basic goals of medical treatment are to maintain fluid,
      electrolyte, and nutrient balances and to make appropriate modifications in
      disease management to avoid side effects. Various definitions have been proposed
      for SBS and intestinal failure within the medical literature, but many focus on
      different aspects of the conditions, leading to confusion. In the past,
      identifying the cause of intestinal failure was of little consequence, because
      all patients were managed on total parenteral nutrition at home. However, with
      the recent development of medical therapies such as recombinant growth hormone,
      octreotide, and glucagon-like peptide-2 analogues and with improvements in small
      bowel transplantation, many patients can be made nutritionally autonomous. To
      evaluate the relative efficacy of these therapies, there is now a need to develop
      consensus definitions so that patients can be properly categorized before
      therapy. To this end, a group of experts on the subject was convened to develop
      the following new definitions: "Intestinal failure results from obstruction,
      dysmotility, surgical resection, congenital defect, or disease-associated loss of
      absorption and is characterized by the inability to maintain protein-energy,
      fluid, electrolyte, or micronutrient balance." "Short-bowel syndrome results from
      surgical resection, congenital defect, or disease-associated loss of absorption
      and is characterized by the inability to maintain protein-energy, fluid,
      electrolyte, or micronutrient balances when on a conventionally accepted, normal
      diet."

PMID- 16431299
TI  - Enteric microbial flora, bacterial overgrowth, and short-bowel syndrome.
AB  - Small intestinal bacterial overgrowth (SIBO) occurs commonly in short-bowel
      syndrome (SBS) and, in some instances, may result in significant problems. SIBO
      is characterized by a variety of signs and symptoms resulting from nutrient
      malabsorption caused by an increased number and/or type of bacteria in the small
      intestine. The anatomic and physiologic changes that occur in SBS together with
      medications commonly used in these patients facilitate the development of SIBO.
      Because many aspects related to SIBO in the SBS population remain poorly
      understood, it was our aim to review the current understanding of the gut flora
      and issues related to SIBO occurring in SBS.

PMID- 16431300
TI  - Pharmacogenomics in inflammatory bowel disease.
AB  - Inherited variations in the nucleotide sequence of genes influence how individual
      patients respond to drugs. Most commonly, clinically significant genetic
      variations consist of single nucleotide polymorphisms (SNPs) within genes that
      affect drug disposition or drug targets. Up to now, relatively few clinically
      important examples of inherited traits that affect drug responses have been
      studied in detail. However, one of the well-characterized examples is highly
      relevant to inflammatory bowel disease therapeutics, that of thiopurine
      methyltransferase pharmacogenetics. Individuals with 2 normal alleles of the gene
      encoding thiopurine methyltransferase metabolize and clear thiopurines such as
      azathioprine and 6-mercaptopurine rapidly. Individuals with 1 normal and 1
      variant allele are intermediate, whereas those with 2 variant alleles clear
      thiopurines very slowly. Intermediate and slow metabolizers are predisposed to
      have high active thiopurine drug levels and develop bone marrow suppression.
      Genomic era technology permits determination of large numbers of SNPs in large
      numbers of individuals. This capability is allowing the field of pharmacogenomics
      to become one of the most productive interfaces in translational biomedical
      research at present. By using high-throughput SNP genotyping, combined with
      careful phenotypic characterization of disease, pharmacogenomic research carries
      the potential of identifying individual biomarkers that predict the relative
      likelihood of benefit or risk from a therapeutic intervention. If this promise
      can be realized, pharmacogenomics will deliver the opportunity for personalized
      medicine.

PMID- 16431301
TI  - Hepatocellular carcinoma: patients with increasing alpha-fetoprotein but no mass
      on ultrasound.

PMID- 16431302
TI  - Detecting dysplasia with optical coherence tomography.

PMID- 16431303
TI  - Optical coherence tomography to identify intramucosal carcinoma and high-grade
      dysplasia in Barrett's esophagus.
AB  - BACKGROUND & AIMS: Optical coherence tomography (OCT) is an optical technique
      that produces high-resolution images of the esophagus during endoscopy. OCT can
      distinguish specialized intestinal metaplasia (SIM) from squamous mucosa, but
      image criteria for differentiating intramucosal carcinoma (IMC) and high-grade
      dysplasia (HGD) from low-grade dysplasia (LGD), indeterminate-grade dysplasia
      (IGD), and SIM without dysplasia have not been validated. The purpose of this
      study was to establish OCT image characteristics of IMC and HGD in Barrett's
      esophagus. METHODS: Biopsy-correlated OCT images were acquired from patients with
      Barrett's esophagus undergoing endoscopic surveillance. Two pathologists rendered
      consensus diagnoses of the biopsy specimens. A blinded investigator reviewed the
      biopsy-correlated OCT images and scored each for surface maturation and gland
      architecture. For each image the scores were summed to determine an OCT
      "dysplasia index." RESULTS: A total of 177 biopsy-correlated images were
      analyzed. The corresponding histopathology diagnosis was IMC/HGD in 49 cases, LGD
      in 15, IGD in 8, SIM in 100, and gastric mucosa in 5. A significant relationship
      was found between a histopathologic diagnosis of IMC/HGD and scores for each
      image feature (dysplasia index [Spearman correlation coefficient, r = 0.50, P <
      .0001], surface maturation [r = 0.48, P < .0001], and gland architecture [r =
      0.41, P < .0001]). When a dysplasia index threshold of >or=2 was used, the
      sensitivity and specificity for diagnosing IMC/HGD were 83% and 75%,
      respectively. CONCLUSIONS: An OCT image scoring system based on histopathologic
      characteristics has the potential to identify IMC and HGD in Barrett's esophagus.

PMID- 16431304
TI  - Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes
      relationship to azathioprine-induced myelosuppression.
AB  - BACKGROUND & AIMS: The use of azathioprine (AZA) in inflammatory bowel disease
      (IBD) patients is limited by toxicity, which occurs in up to 20% of treated
      patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine
      triphosphate pyrophosphatase (ITPA) genes have been associated with the
      occurrence of AZA-related toxicity. The aim of our study was to determine the
      relative contribution of ITPA and TPMT mutations to the development of toxicity
      induced by AZA treatment in IBD patients. METHODS: ITPA(94C>A, IVS2+21A>C) and
      TPMT (238G>C, 460G>A, and 719A>G) genotypes were assessed in 262 IBD patients
      (159 females, 103 males; 67 patients with ulcerative colitis, 195 patients with
      Crohn's disease) treated with AZA and were correlated with the development of
      leukopenia and hepatotoxicity. RESULTS: Leukopenia (leukocyte count, <3.0 x
      10(9)/L) was observed in 4.6% of treated patients. The frequencies of mutant ITPA
      94C>A and TPMT alleles were significantly higher in the leukopenic population
      compared with patients without leukopenia (16.7% and 5.4%, respectively, for ITPA
      94C>A, and 20.8% and 4%, respectively, for TPMT). Moreover, the ITPA 94C>A and
      TPMT mutations predicted leukopenia: ITPA 94C>A odds ratio, 3.504; 95% confidence
      interval, 1.119-10.971 (P = .046); TPMT odds ratio, 6.316; 95% confidence
      interval, 2.141-18.634 (P = .004). Neither TPMT nor ITPA genotype predicted
      hepatotoxicity. CONCLUSIONS: ITPA 94C>A and TPMT polymorphisms are associated
      with AZA-related leukopenia in IBD patients.

PMID- 16431306
TI  - Gastrointestinal tolerability of lumiracoxib in patients with osteoarthritis and
      rheumatoid arthritis.
AB  - BACKGROUND & AIMS: The aim of this study was to evaluate the gastrointestinal
      safety of lumiracoxib, a novel selective cyclooxygenase-2 inhibitor. METHODS:
      Results from 15 Phase II and III randomized studies of lumiracoxib in
      osteoarthritis and rheumatoid arthritis were pooled. Patients received
      lumiracoxib (200/400 mg/day), celecoxib (200/400 mg/day), rofecoxib (25 mg once
      daily), diclofenac (75 mg twice daily), ibuprofen (800 mg 3 times daily),
      naproxen (500 mg twice daily), or placebo. Outcome measures included the
      incidence of definite or probable ulcer complications (perforations,
      obstructions, or bleedings as confirmed by an adjudication committee) and
      symptomatic upper gastrointestinal ulcers, the incidence of prespecified
      gastrointestinal adverse events, and the discontinuation rate caused by adverse
      events. All suspected ulcer complications in these 15 studies were adjudicated
      prospectively. Data from 2 endoscopic studies were pooled separately to assess
      the cumulative incidence of gastroduodenal ulcers >or=3 mm in diameter. RESULTS:
      Symptomatic upper gastrointestinal ulcers and ulcer complications were reduced
      nearly 10-fold with lumiracoxib (1.7 events per 100 patient-years [95% confidence
      interval, 1.09-2.39]) compared with nonselective nonsteroidal anti-inflammatory
      drugs (13.7 events per 100 patient-years [95% confidence interval, 9.47-18.82]).
      Symptomatic ulcer frequency was markedly lower with lumiracoxib (0.4%) than with
      nonselective nonsteroidal anti-inflammatory drugs (2.5%). Discontinuation rates
      due to gastrointestinal adverse events were higher for nonselective nonsteroidal
      anti-inflammatory drugs (8.4%) than for lumiracoxib (3.3%). In the endoscopy
      analysis, the cumulative frequency of ulcers >or=3 mm in diameter was reduced by
      >70% for lumiracoxib versus ibuprofen. CONCLUSIONS: Lumiracoxib exhibited a
      gastrointestinal safety profile superior to nonselective nonsteroidal anti
      inflammatory drugs.

PMID- 16431305
TI  - Treatment of patients with persistent heartburn symptoms: a double-blind,
      randomized trial.
AB  - BACKGROUND & AIMS: Common treatment practices in patients who continue to be
      symptomatic on proton pump inhibitor once-daily treatment include either
      increasing the dosage or the use of supplemental medication. This trial's purpose
      was to compare 2 therapeutic strategies, increasing the proton pump inhibitor
      dosage to twice daily versus switching to another proton pump inhibitor, in
      patients with persistent heartburn while receiving standard-dose proton pump
      inhibitor therapy. METHODS: This multicenter, randomized, double-blind, double
      dummy trial included patients with persistent heartburn symptoms while receiving
      therapy with lansoprazole 30 mg once daily. Patients were randomly assigned to
      treatment for 8 weeks with either single-dose esomeprazole (40 mg once daily) (n
      = 138) or lansoprazole 30 mg twice daily (n = 144). The primary efficacy variable
      was the percentage of heartburn-free days from day 8 to the end of treatment.
      RESULTS: Single-dose esomeprazole was at least as effective as twice-daily
      lansoprazole for the primary end point of percentage of heartburn-free days
      during the study period (54.4% and 57.5%, respectively). Symptom scores improved
      from baseline in similar numbers of patients for heartburn (83.3% of patients in
      each group), acid regurgitation (76.8% vs 72.9%, P = .58), and epigastric pain
      (67.4% vs 61.1%, P = .32), and rescue antacid use was also similar (0.4
      tablets/day vs 0.5 tablets/day, P = .50). CONCLUSIONS: Switching patients with
      persistent heartburn on a standard-dose proton pump inhibitor to a different
      proton pump inhibitor was as effective as increasing the proton pump inhibitor
      dosage to twice daily for controlling heartburn symptoms.

PMID- 16431307
TI  - Longitudinal follow-up of children with functional nonretentive fecal
      incontinence.
AB  - BACKGROUND & AIMS: Functional nonretentive fecal incontinence (FNRFI),
      incontinence in the absence of signs of fecal retention, is a frustrating
      phenomenon in children. No data on long-term outcome are available. The aim was
      to investigate the long-term outcome of FNRFI patients after intensive medical
      treatment. METHODS: Between 1990 and 1999, 119 patients (96 boys) with FNRFI were
      enrolled in 2 prospective, randomized trials investigating the effect of
      biofeedback training and/or laxative treatment. Follow-up (FU) was performed at 6
      months, 1 year, and thereafter annually until September 2004. A standardized
      questionnaire was used to evaluate symptoms. Success was defined as a fecal
      incontinence frequency <1 per 2 weeks. RESULTS: Median age (25th-75th
      percentiles) was 9.2 years (range, 7.9-11.6 years). A 90% FU was achieved at all
      stages of the study. After 2 years of intensive therapy, 33 of 112 (29.5%)
      patients were successfully treated. The cumulative success percentage after 7
      years of FU was 80%. At the biologic ages of 12 and 18 years, 49.4% (40/81) and
      15.5% (9/58), respectively, of the patients still had fecal incontinence.
      Duration of fecal incontinence, with 4 years of age as the starting age for fecal
      incontinence (when a child should be toilet trained), was not related to
      successful outcome or relapse. Relapse occurred in 37% of patients. CONCLUSIONS:
      Only 29% of the patients with FNRFI were successfully treated after 2 years of
      intensive treatment. Despite recovery in the majority of patients beyond puberty,
      at age 18 years, 15% continued to have fecal incontinence.

PMID- 16431308
TI  - Intestinal disease in Hermansky-Pudlak syndrome: occurrence of colitis and
      relation to genotype.
AB  - BACKGROUND & AIMS: Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive
      disorder characterized by oculocutaneous albinism and platelet dysfunction,
      results from mutations in 1 of at least 7 different genes. Some patients develop
      a fatal pulmonary fibrosis and others a disabling colitis. This study aimed to
      document the occurrence of colitis among HPS patients, characterize
      gastrointestinal tract involvement in HPS, and analyze the distribution of
      colitis among HPS genotypes. METHODS: Of the 122 HPS patients followed at the
      National Institutes of Health Clinical Center between 1993 and 2005, 24 were
      evaluated by endoscopy for gastrointestinal complaints. The histology of
      gastrointestinal biopsies was retrospectively examined to assess for inflammatory
      changes, granulomata, and pigmented macrophages. These data were compared with
      symptoms and HPS genetic subtypes. RESULTS: At colonoscopy, 7 of 23 patients
      (30%) had endoscopic mucosal abnormalities, including nodularity, erythema,
      petechiae, or erosions. Six of these 7 patients (86%) had findings of colitis on
      biopsy. Of the 16 patients with normal-appearing colonic mucosa, 2 patients (12%)
      had colitis on biopsy. Pigmented macrophages were also observed in the colonic
      lamina propria in 16 of the 23 patients (70%). Of the 8 patients with confirmed
      colitis, 7 had the HPS-1 subtype, and 1 had the HPS-4 subtype. CONCLUSIONS: There
      is an increased frequency of colitis in our population of 122 HPS patients
      (8/122, 7%) and in HPS patients referred specifically for symptom evaluation
      (8/24, 33%). Colitis was found in patients with HPS-1 and HPS-4 genotypes.

PMID- 16431310
TI  - Towards the ideal quantitative pancreatic function test: analysis of test
      variables that influence validity.
AB  - BACKGROUND & AIMS: Although pancreatic stimulation tests quantify acinar and
      ductal exocrine pancreatic function, no standard methodology exists. We evaluated
      the impact of several variables on test accuracy. METHODS: We performed a
      retrospective analysis of pancreatic stimulation tests, which involved continuous
      stimulation with cholecystokinin and secretin, 3 sampling periods (20-min each),
      and perfusion markers to correct for intestinal losses. Results were recalculated
      using the following variables: no correction for losses; shortened sampling time
      (20-min); no correction and shortened sampling time; and enzyme concentration. We
      examined how these variables influenced measurements of pancreatic secretion and
      classification of pancreatic function status (sufficient or insufficient).
      RESULTS: We analyzed 363 tests in control patients (20), and patients with cystic
      fibrosis (137), Shwachman-Diamond syndrome (40), or other pancreatic or
      intestinal disorders (166). Recovery of pancreatic juice varied markedly between
      tests (median, 59%; range, 4%-106%) and was significantly poorer during the first
      20-minute period compared with the 2 subsequent periods (P < .01). Failure to
      correct for intestinal losses underestimated secretory capacity (median trypsin
      output reduced by >50%, P < .0001) and shortened sampling time increased test
      variability. Both variables together resulted in greater discrepancies. More than
      25% of the pancreatic-sufficient patients with impaired pancreatic function were
      misclassified as pancreatic insufficient when uncorrected output plus a shortened
      sampling time or enzyme concentration were used to define categories.
      CONCLUSIONS: Pancreatic function tests using brief aspiration periods without
      marker perfusion or measures of concentration greatly underestimate pancreatic
      secretory capacity and misclassify the clinical status of an unacceptably large
      number of patients.

PMID- 16431309
TI  - Risk factors for diseases of ileal pouch-anal anastomosis after restorative
      proctocolectomy for ulcerative colitis.
AB  - BACKGROUND & AIMS: Although pouchitis is considered the most common adverse
      sequela of ileal pouch-anal anastomosis (IPAA), inflammatory and noninflammatory
      conditions other than pouchitis are increasingly being recognized. The risk
      factors for these non-pouchitis conditions, including Crohn's disease (CD) of the
      pouch, cuffitis, and irritable pouch syndrome (IPS), have not been studied. The
      aim of this study was to assess risk factors for inflammatory and noninflammatory
      diseases of IPAA in a tertiary care setting. METHODS: The study consisted of 240
      consecutive patients who were classified as having healthy pouches (N = 49),
      pouchitis (N = 61), CD of the pouch (N = 39), cuffitis (N = 41), or IPS (N =50).
      Demographic and clinical features were assessed to determine risk factors for
      each of these conditions by using logistic regression analysis. RESULTS: Risk
      factors remaining in the final logistic regression models were for pouchitis:
      IPAA indication for dysplasia (odds ratio [OR], 3.89; 95% confidence interval
      [CI], 1.69-8.98), never having smoked (OR, 5.09; 95% CI, 1.01-25.69), no use of
      anti-anxiety agents (OR, 5.19; 95% CI, 1.45-18.59), or use of NSAIDs (OR, 3.24;
      95% CI, 1.71-6.13); for CD of the pouch: a long duration of IPAA (OR, 1.20; 95%
      CI, 1.12-1.30) and current smoking (OR, 4.77; 95% CI, 1.39-16.25); for cuffitis:
      arthralgias (OR, 4.13; 95% CI, 1.91-8.94) and younger age (OR, 1.16; 95% CI, 1.01
      1.33); and for IPS: use of antidepressants (OR, 4.17, 95% CI, 1.95-8.92) or anti
      anxiety agents (OR, 3.21; 95% CI, 1.34-7.47). CONCLUSIONS: The majority of risk
      factors for the 4 inflammatory and noninflammatory conditions of IPAA are
      different, suggesting that each of these diseases has a different etiology and
      pathogenesis. The identification and modification of these risk factors might
      help patients and clinicians to make a preoperative decision for IPAA, reduce
      IPAA-related morbidity, and improve response to treatment.

PMID- 16431311
TI  - A single-center experience of endoscopic ultrasonography for enlarged pancreas on
      computed tomography.
AB  - BACKGROUND & AIMS: The clinical significance of "fullness" or enlargement of the
      pancreas (FP/EP) is not well established. The objective of this study was to
      report our experience with endoscopic ultrasonography (EUS) in evaluating
      patients referred for FP/EP found on computed tomography (CT). METHODS: Patients
      referred to our center for EUS evaluation of FP/EP between January 1998 and
      December 2003 were studied. Patient demographics, clinical history, endoscopic
      findings, and follow-up were recorded. Multivariate analysis was used to identify
      predictors of pancreatic malignancy. RESULTS: A total of 50 patients: 46% (23/50)
      male, mean age 59 years (range, 18-90) made up our studied population. EUS
      demonstrated normal findings in 42% (21/50), prominent ventral anlage
      (embryologic variant) in 14% (7/50), and chronic pancreatitis in 22% (11/50). In
      22% (11/50), a suspicious mass was noted and fine-needle aspiration (FNA) was
      performed. Cytology revealed chronic inflammation in 7 patients, while
      adenocarcinoma was found in the remaining 4. Median follow-up was 27 months, and
      the diagnosis did not change in any of the 50 patients. There were no procedure
      related complications. After multivariant regression analysis, the factors that
      were statistically associated with malignancy were a CA19-9 level >300 (P =
      .0002) and weight loss (P < .006). CONCLUSIONS: The majority of patients
      presenting with FP/EP had benign disease, but 8% had pancreatic cancer. Elevated
      CA19-9 and weight loss were predictive of pancreatic malignancy. EUS and EUS-FNA
      are safe and accurate diagnostic tests and can play an important role in
      evaluating patients with FP/EP.

PMID- 16431312
TI  - Racial differences in survival of hepatocellular carcinoma in the United States:
      a population-based study.
AB  - BACKGROUND & AIMS: Survival after hepatocellular carcinoma (HCC) diagnosis is
      generally dismal, but there are patients with more favorable outcomes. Racial
      variation in survival of patients with HCC could be associated with observed
      differences in survival; however this has not been previously examined. METHODS:
      During 1987-2001, HCC patients were identified from 9 Surveillance, Epidemiology,
      and End-Results registries. One- and 3-year survival rates were calculated and
      compared by race. Models were constructed to examine the effects of race on the
      mortality risk. RESULTS: Asians had the highest 1- and 3-year observed and
      relative survival, followed by whites, Hispanics, and blacks. Compared with
      whites, Asians (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.11-1.69)
      were more likely to receive local or surgical therapy, whereas blacks (OR, 0.62;
      95% CI, 0.49-0.78) and Hispanics (OR, 0.81; 95% CI, 0.60-1.09) were less likely
      to receive therapy. Adjusting for differences in receipt of therapy, stage of
      HCC, year of diagnosis, and other demographics, Asians (hazard rate [HR], 0.84;
      95% CI, 0.78-0.91) maintained a lower mortality risk compared with whites. In
      adjusted models, Hispanics (HR, 1.13; 95% CI, 1.03-1.24) maintained a higher
      mortality risk, whereas the mortality risk for blacks became nonsignificant
      different from whites (HR, 1.06; 95% CI, 0.99-1.14). Last, a 22% improvement in
      survival was observed between 1987-1991 and 1997-2001, which was mostly explained
      by increased receipt of local or surgical therapy. CONCLUSIONS: We observed
      significant racial variation in survival. These variations in survival are partly
      explained by a lower likelihood of receipt of therapy and more advanced HCC at
      diagnosis among blacks and Hispanics.

PMID- 16431314
TI  - Intraabdominal abscess with gauze.

PMID- 16431313
TI  - Prognostic significance of simultaneous measurement of three tumor markers in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: We conducted a prospective study to evaluate the significance
      of simultaneous measurement of 3 currently used tumor markers in the evaluation
      of tumor progression and prognosis of patients with hepatocellular carcinoma
      (HCC). METHODS: Three tumor markers for HCC, alpha-fetoprotein (AFP), Lens
      culinaris agglutinin A-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy
      prothrombin (DCP), were measured in the same serum samples obtained from 685
      patients at the time of initial diagnosis of HCC. Positivity for AFP >20 ng/dL,
      AFP-L3 >10% of total AFP, and/or DCP >40 mAU/mL was determined. In addition,
      tumor markers were measured after treatment of HCC. RESULTS: Of the 685 patients,
      337 (55.8%) were positive for AFP, 206 (34.1%) were positive for AFP-L3, and 371
      (54.2%) were positive for DCP. In a comparison of patients positive for only 1
      tumor marker, patients positive for AFP-L3 alone had a greater number of tumors,
      whereas patients positive for DCP alone had larger tumors and a higher prevalence
      of portal vein invasion. When patients were compared according to the number of
      tumor markers present, the number of markers present clearly reflected the extent
      of HCC and patient outcomes. The number of markers present significantly
      decreased after treatment. CONCLUSIONS: Tumor markers AFP-L3 and DCP appear to
      represent different features of tumor progression in patients with HCC. The
      number of tumor markers present could be useful for the evaluation of tumor
      progression, prediction of patient outcome, and treatment efficacy.

PMID- 16431315
TI  - Laparoscopy in an enormous ovarian cyst.

PMID- 16431316
TI  - Implementation of advanced laparoscopy into daily gynecologic practice:
      difficulties and solutions.
AB  - BACKGROUND: The implementation of laparoscopy into Dutch gynecologic practice is
      slow. This study was conducted to assess the current state of laparoscopy, to
      identify factors influencing the implementation and to find solutions toward a
      better implementation. METHODS: In 2003 a questionnaire was sent to all 151
      gynecologists who finished residency within the previous 5 years. The
      questionnaire addressed practice demographics, performance of laparoscopy,
      factors influencing use of laparoscopy in practice and means of obtaining
      laparoscopic skills after residency. RESULTS: Of 151 gynecologists, 124 (82%)
      responded, 46 (37%) male and 78 (63%) female. Mean age was 39 years (range 32-47
      years). Respondents (73%) believed they were adequately trained during residency
      for basic laparoscopic procedures, but not for the more advanced procedures
      (82%). Lack of caseload, lack of being a primary surgeon, and lack of simulator
      training caused the deficiency of laparoscopic skills at the end of the
      residency. Causes of the slow implementation were long operating time, lack of
      attention for laparoscopy during residency, and budgetary problems, but not the
      financial compensation for gynecologists. In current practice, only 9% believed
      they reached their preferred level of competence. Hiring an advanced laparoscopic
      gynecologist was believed to be the best opportunity to reach the preferred level
      of competence. A minority of respondents supported a referral system or
      fellowship program. CONCLUSIONS: Basic laparoscopy is sufficiently mastered
      during residency training; however, advanced laparoscopy is not. More emphasis
      should be placed on laparoscopic training of advanced procedures during residency
      and for gynecologists in practice. Hiring a gynecologist with advanced
      laparoscopic skills is expected to be the solution for this problem. However, a
      referral system or fellowship program is not.

PMID- 16431317
TI  - Endoscopy teaching in Canada: a survey of obstetrics and gynecology program
      directors and graduating residents.
AB  - OBJECTIVE: To examine the current state of basic and advanced gynecologic
      endoscopy teaching in Canadian Obstetrics and Gynecology (Ob/Gyn) residency
      programs. METHODS: On Institutional Research Board approval, 2 pretested
      anonymous questionnaires were developed: one distributed to all Canadian Ob/Gyn
      program directors and a second to graduating residents (Canadian Task Force
      classification III). Two mailings were sent to maximize response, and some
      department chairs received personal telephone calls by the senior author to
      encourage participation. Residents on maternity leave were excluded from the
      study. RESULTS: Fifteen of 16 (94%) program directors, and 47 of 62 (76%)
      residents participated. Directors expect all residents to be knowledgeable and
      competent performing basic endoscopic procedures on graduation. However,
      considerable variation exists among programs that teach advanced endoscopy. Some
      of the more important factors limiting integration of advanced endoscopic
      teaching include paucity of trained faculty, lack of attending interest, scarcity
      of operating time, and financial constraints. Most graduating residents consider
      undertaking additional gynecologic endoscopy fellowships. CONCLUSION: Most Ob/Gyn
      program directors and graduating residents consider endoscopic surgery essential
      to contemporary practice. There is consensus to improve resident teaching in
      gynecologic endoscopy and commitment to better prepare future practitioners to
      ensure patient safety. Paucity of trained faculty and fiscal constraints appear
      to be important limiting factors.

PMID- 16431318
TI  - Laparoscopic obturator nerve neurolysis after pelvic lymphadenectomy.
AB  - Postoperative neuropathy is a known complication of major pelvic oncologic
      surgery. Obturator nerve injury complicating pelvic lymph node dissection has
      been reported in the literature. Severity and duration of symptoms are determined
      by the severity of the initial nerve lesion. Different management options have
      been described in the literature. We report here on a patient who developed right
      obturator neuropathy after pelvic lymphadenectomy. Initial management by physical
      therapy was unsuccessful, and the patient underwent a successful laparoscopic
      surgical neurolysis. Whereas preventive measures remain essential to avoid any
      nerve injury, this case illustrates the use of laparoscopy to perform neurolysis
      with a favorable outcome; therefore, persistent pain or motor loss should
      motivate at least surgical exploration that can be done with low morbidity by
      laparoscopy.

PMID- 16431319
TI  - Total laparoscopic radical hysterectomy and pelvic lymphadenectomy using harmonic
      shears.
AB  - STUDY OBJECTIVE: To describe the feasibility and outcome of total laparoscopic
      radical hysterectomy with or without pelvic lymphadenectomy for patients with
      stage I cervical cancer or severe pelvic endometriosis using harmonic shears as
      the sole instrument for dissection, division, and maintenance of hemostasis of
      all major surgical pedicles. DESIGN: Retrospective review (Canadian Task Force
      classification II-2). SETTING: University hospital and affiliate institutions.
      PATIENTS: Seven patients who underwent total laparoscopic radical hysterectomy
      using harmonic shears for International Federation of Gynecology and Obstetrics
      stage IA2 to IB1 cervical cancer and pelvic endometriosis at our institution or
      affiliate hospital from January 2004 through February 2005. INTERVENTION: A
      retrospective review of patients that underwent total laparoscopic radical
      hysterectomy with or without pelvic lymphadenectomy at our institution using
      harmonic shears was performed. Information regarding preoperative,
      intraoperative, and postoperative events was recorded and analyzed. MEASUREMENTS
      AND MAIN RESULTS: Pelvic lymphadenectomy was performed in all cancer cases. Mean
      patient age was 40 years (range 30-53 years). Mean estimated blood loss was 143
      mL (range 100-200 mL). Mean operating time was 293 minutes (range 255-385
      minutes). Mean pelvic node count was 27.8 (range 24-34) for cancer cases. Mean
      hospital stay was 3.2 days (range 2-7 days). One patient developed a vaginal cuff
      abscess postoperatively that was managed conservatively with drainage in the
      office setting followed by intravenous antibiotics. Another patient developed
      urinary retention for 2 weeks after surgery. There were no other intraoperative
      or postoperative complications. CONCLUSION: Total laparoscopic radical
      hysterectomy with pelvic lymphadenectomy using harmonic shears is a technically
      feasible and safe procedure. Larger studies and long-term follow-up are required
      to determine the oncologic outcomes of these patients.

PMID- 16431320
TI  - Analysis of survival after laparoscopic-assisted vaginal hysterectomy compared
      with the conventional abdominal approach for early-stage endometrial carcinoma: a
      review of the literature.
AB  - STUDY OBJECTIVE: To assess potential differences in perioperative features and
      survival between laparoscopic-assisted vaginal hysterectomy and conventional
      transabdominal hysterectomy in stage I endometrial cancer. DESIGN: Retrospective,
      nonrandomized clinical study (Canadian Task Force classification II-2). SETTING:
      Acute-care, teaching hospital. PATIENTS: A total of 370 patients undergoing
      hysterectomy and bilateral salpingo-oophorectomy with surgical staging for
      primary treatment for clinical stage I endometrial cancer from January 1995
      through June 2001. INTERVENTION: Clinical outcomes and survival in patients
      treated with laparoscopic-assisted vaginal hysterectomy (n = 55) and hysterectomy
      using the conventional abdominal approach (n = 315) were compared. MEASUREMENTS
      AND MAIN RESULTS: Baseline characteristics and histopathologic variables were
      similar in both groups. A total of 91.4% of patients underwent pelvic
      lymphadenectomy and 49.7% paraaortic lymphadenectomy. The median follow-up was
      38.1 months. Blood loss, blood transfusions required, and length of stay were
      significantly lower in the laparoscopic group, but surgical time was
      significantly longer. The mean number of pelvic and aortic nodes recovered was
      higher in the laparoscopic group (p < .001). Differences in overall and
      recurrence-free survival rates were not observed. CONCLUSION: Surgical staging of
      early-stage endometrial cancer by laparoscopic-assisted vaginal hysterectomy is
      feasible, with lower perioperative morbidity and shorter hospital stay compared
      with transabdominal hysterectomy. Prognosis and survival were not affected by the
      laparoscopic vaginal approach to hysterectomy.

PMID- 16431322
TI  - Management of patients with ectopic pregnancy with massive hemoperitoneum by
      laparoscopic surgery with intraoperative autologous blood transfusion.
AB  - STUDY OBJECTIVE: To evaluate the feasibility and safety of surgical laparoscopy
      with intraoperative autologous blood transfusion for ectopic pregnancy with
      massive hemoperitoneum. DESIGN: Retrospective analysis (Canadian Task Force
      classification II-1). SETTING: Department of gynecology at a general hospital.
      PATIENTS: Seventeen consecutive patients with ectopic pregnancy with massive
      hemoperitoneum. INTERVENTION: Laparoscopic surgery with salvage device-based
      intraoperative autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: From
      January 2000 through June 2005, one hundred and twelve women with ectopic
      pregnancy (interstitial/cornual: 4; isthmic: 18; ampullary: 86; and ovarian: 4)
      were treated by laparoscopic surgery. Seventeen patients who demonstrated more
      than 501 g of intraabdominal bleeding were classified as having massive
      hemoperitoneum and retrospectively analyzed. Site of pregnancy in these 17
      patients was interstitial/cornual: 3; isthmic: 5; ampullary: 7; and ovarian: 2.
      Except for two women with tubal abortion of ampullary pregnancy, all other
      patients had rupture at the pregnancy site. During laparoscopic surgery, blood
      pooled in the abdominal cavity was collected by an irrigation and aspiration
      procedure, and sent to an autologous blood-salvage device to make concentrated
      red blood cell solution. Processed blood was immediately transfused back to the
      patient through a leukocyte reduction filter. The mean amount of estimated
      intraabdominal bleeding, which was calculated by the difference between the
      volumes of aspirated and irrigated fluids, was 1362.1 +/- 491.4 g, and the mean
      volume of reinfused processed blood was 680.6 +/- 209.5 g. No patient received
      banked blood at any time. The degree of hemoperitoneum was well correlated with
      the shock index calculated by dividing the heart rate by systolic blood pressure
      at triage (r = 0.72; 95% CI 0.37-0.89; p = .001). In all cases of massive
      hemoperitoneum, there was no need for laparotomic conversion, and homologous
      blood transfusion was avoided. CONCLUSIONS: Even in women with ectopic pregnancy
      with massive hemoperitoneum, laparoscopic surgery can be safely conducted by
      experienced laparoscopists with intraoperative autologous blood transfusion if
      hemodynamic stability is achieved by perioperative management.

PMID- 16431321
TI  - Mechanisms of thermal injury to the lower genital tract with radiofrequency
      resectoscopic surgery.
AB  - STUDY OBJECTIVE: Identification of mechanisms of thermal injury to the lower
      genital tract during radiofrequency (RF) resectoscopic surgery. DESIGN:
      Laboratory comparative study using uterovaginal tissue models. SETTING:
      University surgical laboratory. PATIENTS: No patients involved. INTERVENTIONS: A
      tissue model was created to simulate the uterus, contiguous posterior vaginal
      wall, and the introitus. Instrumentation included a RF electrosurgical generator;
      a continuous-flow resectoscope; and rollerball electrodes, both intact and with
      insulation defects created in a standardized fashion. The resectoscope was
      serially activated, varying electrode insulation defects and RF waveforms and
      wattage, both in open-circuit conditions, with or without cervical contact, and
      with variable amounts of the external sheath within the simulated cervical canal.
      The cervix was either overdilated or minimally dilated so that the surrogate
      cervical tissue was snug to the external sheath. After activation of the
      generator, the external sheath was brought into contact with the proximal vagina
      and perineum, any visible arcing was noted, and tissue effects were visually
      graded according to a zero-to-three scale. MEASUREMENTS AND MAIN RESULTS: When
      the resectoscope was in contact with the cervix, the prerequisites for vaginal
      injury included cervical overdilation, a proximal electrode insulation defect,
      and less than 2 cm of the external sheath in the canal. There was greater risk
      with larger electrode insulation defects located beside the telescope, and there
      was a greater degree of coupling and injury with high voltage outputs.
      CONCLUSION: The incidence of vaginal and perineal burns associated with unipolar
      RF resectoscopes can likely be minimized by careful attention to technique.

PMID- 16431323
TI  - Adhesions and pain in women with first diagnosis of endometriosis: results from a
      cross-sectional study.
AB  - OBJECTIVE: To analyze the relationship between pain and presence, site, and type
      of adhesions in women with endometriosis. METHODS: This was a multicenter,
      observational cross-sectional study. Eligible for the study were women with
      endometriosis and pelvic pain, consecutively observed during the study period at
      the collaborating centers. A total of 574 women entered the study. RESULTS:
      Adhesions were observed in 81.9% of cases (470 women). The frequency was lower in
      women with endometriosis at stage I-II (65%) and higher in women with stage III
      IV (88%); this difference was statistically significant (p < .01). The frequency
      of adhesions was lower in women with ovarian endometriosis (74%) and higher in
      those with ovarian and peritoneal endometriosis (87%) or other sites (96%) (p <
      .01). The presence of adhesions was associated with higher mean visual analog
      scale (VAS) scores and median multidimensional scale ratings in women with
      ovarian disease and with stage I-II disease. Women with ovarian adhesions
      reported higher VAS and multidimensional scale scores (p < .05) than women with
      peritoneal adhesions or adhesions in other sites. CONCLUSIONS: The results of
      this study suggest that there is no overall association between the presence of
      adhesions and the degree of pain in women with endometriosis. The data suggests
      that there may be an association between adhesions and pain in women with ovarian
      and Type I-II endometriosis. However, these associations were no longer
      significant after correction for multiple comparisons. Further research is
      indicated to test these associations.

PMID- 16431324
TI  - Audit of morbidity and mortality rates of 1792 hysterectomies.
AB  - STUDY OBJECTIVE: To audit morbidity and mortality rates of laparoscopic,
      abdominal, and vaginal hysterectomy. DESIGN: Retrospective review of monthly
      morbidity and mortality rates (Canadian Task Force classification II-2). SETTING:
      University teaching hospital. PATIENTS: One thousand seven hundred ninety-two
      women who underwent hysterectomy for benign, nonobstetric indications at the Sir
      Mortimer B. Davis-Jewish General Hospital. INTERVENTIONS: Laparoscopic
      supracervical (LASH), vaginal (VH), and abdominal (AH) hysterectomies. MAIN
      OUTCOME MEASURES: Morbidity outcomes of different types of hysterectomy.
      Reoperation, admission to the intensive care unit, discordant diagnosis, and
      prolonged hospitalization also were evaluated. RESULTS: We studied 223 cases of
      LASH, 1349 AH, and 220 VH. The overall hysterectomy-related morbidity rate was
      6.1%. The rate of morbidity was higher in the LASH group (9.4%) than in the AH
      group (5.2%, p <.01), but no significant difference was noted between AH and VH
      (8.6%). The incidence of intraoperative bowel injury was 0.4% in the LASH group
      (a trocar injury in a patient) and 0.3% in the AH group. Bladder injury was
      encountered in two patients in the LASH group (0.9%) and in another two in the AH
      group (0.1%). Ureteral injury occurred in a patient in the AH group (0.07%).
      There were no cases of intraoperative vascular injury. Vaginal hysterectomy was
      associated with more urinary retention and hematoma formation than the other two
      groups. Discordant diagnosis was noted in four cases (two missed endometrial
      cancer, atonic and distended bladder mistaken for an ovarian cyst, and pelvic
      tuberculosis). The conversion rate to laparotomy was 1.7% in the LASH group and
      0.4% in the VH group, and the incidence of reoperation was 0.4% in the AH group.
      CONCLUSIONS: The overall hysterectomy-related morbidity rate in our series is
      6.1%. Compared with other types of hysterectomy, more urinary retention and
      hematoma formation occur after VH. Laparoscopic supracervical hysterectomy is
      associated with a higher morbidity rate than AH; mainly because of conversion to
      laparotomy and blood transfusion.

PMID- 16431326
TI  - Laparoscopic diagnosis of asymptomatic megaureter.
AB  - The rare case of an asymptomatic megaureter in a young woman demonstrates that
      laparoscopy can be helpful in the differential diagnosis for unknown
      retroperitoneal masses. The accurate dissection of the retroperitoneal structures
      together with a thorough knowledge of the retroperitoneal anatomy should always
      be considered in these cases.

PMID- 16431325
TI  - Pilot study assessing robotic laparoscopic hysterectomy and patient outcomes.
AB  - STUDY OBJECTIVE: To examine the operative variables and complications associated
      with robotic-assisted total laparoscopic hysterectomy. DESIGN: Canadian Task
      Force classification II-1. SETTING: Gynecology service affiliated with a major
      cancer center in Southern California. PATIENTS: Twenty women with a benign
      gynecologic condition. INTERVENTION: Robotic-assisted total laparoscopic
      hysterectomy. Patient status was evaluated in terms of operative morbidity,
      length of surgery, anesthesia time, estimated blood loss, and hospital stay.
      MEASUREMENTS AND MAIN RESULTS: Mean operative time was 3.2 hours, and anesthesia
      time was 4 hours. Mean estimated blood loss was 81 mL, and patient postoperative
      hospital stay was 2 days. The complication rate in this study was low. The
      surgical procedure was converted to a laparotomy and abdominal hysterectomy in
      two patients because of poor visualization during robotic-assisted surgery.
      CONCLUSIONS: While the number of patients and nonrandomized nature of this single
      institution experience are insufficient to draw any definitive conclusions
      regarding potential treatment efficacy, the patient postoperative stay and low
      complication rates suggest that this procedure is feasible and promising.
      Additional study comparing the efficacy and cost of robotic laparoscopic
      hysterectomy with standard laparoscopic hysterectomy with a larger patient
      population is warranted.

PMID- 16431327
TI  - Pelvic meningocele can be missed during laparoscopy.
AB  - Pelvic meningocele is an uncommon condition and is frequently asymptomatic. The
      diagnosis easily can be mistaken as ovarian cyst on pelvic sonography. In many
      reported cases, the diagnosis was made during laparotomy for presumed ovarian
      cysts. Myelography, computerized tomography (CT), or magnetic resonance imaging
      (MRI) is useful for definitive diagnosis. A 49-year-old woman, who had a normal
      diagnostic laparoscopy 3 years prior, was referred for a persistent ovarian cyst.
      Repeat laparoscopy revealed a retroperitoneal cyst in the left pelvic sidewall.
      Both ovaries and fallopian tubes were normal. Subsequent CT and MRI were used to
      diagnose pelvic meningocele. We speculate that pelvic meningoceles can be missed
      during laparoscopy due to the increased intraperitoneal pressure and the
      potential reduction in the cerebrospinal fluid pressure at the lumbosacral level.

PMID- 16431328
TI  - Laparoscopic metroplasty for bicornuate uterus.
AB  - This is a case study of a 29-year-old nulliparous woman with a bicornuate uterus
      who had a poor obstetric history in whom we performed a laparoscopic metroplasty.
      She was advised to use barrier contraception for 3 months. A repeat hystero
      laparoscopy performed 3 months later revealed a single large uniform uterine
      cavity without any adhesions. The patient had an incompetent cervical os after
      surgery and was advised to undergo cervical cerclage on conception.

PMID- 16431330
TI  - Nezhat et al. Laparoscopic management of hepatic endometriosis: report of two
      cases and review of the literature.

PMID- 16431329
TI  - Cornual gestation: a systematic literature review and two case reports of a novel
      treatment regimen.
AB  - STUDY OBJECTIVE: To introduce a novel tubal-sparing regimen for the treatment of
      nonruptured cornual pregnancies. DESIGN: Case report and systematic review of the
      literature. SETTING: Tertiary Care University setting. PATIENTS: Two patients
      referred for care in our subspecialty clinic. INTERVENTIONS: Laparoscopic
      surgery, dilation and evacuation, and postoperative methotrexate injection.
      Systematic review of the literature. MEASUREMENTS AND MAIN RESULTS: Both medical
      and surgical treatments for cornual gestation exist; however, each is not without
      its shortcomings. Medical treatment is associated with failure rates that may
      result in uterine rupture and catastrophic hemorrhage. Surgical treatment that
      involves hysterectomy causes a loss of future childbearing capability. Surgical
      treatment that involves resection of the involved cornual region is associated
      with decreased fertility rates and increased rates of uterine rupture in future
      pregnancies. Our treatment regimen is safe and effective and conserves future
      fertility. CONCLUSION: A cornual gestation is one of the most hazardous types of
      ectopic gestation. The diagnosis and treatment of such a pregnancy is challenging
      and constitutes an urgent medical situation. We herein introduce a novel regimen
      for the treatment of nonruptured cornual pregnancies. The existing treatment
      regimens are also systematically reviewed.

PMID- 16431333
TI  - The different faces of shared autoimmunity.
AB  - The concept of shared autoimmunity comprises various forms of disease: rheumatic
      diseases in several members of the same family, the coincidence of autoimmune
      rheumatic with non-rheumatic diseases in relatives of patients, the presence of
      autoantibodies in healthy relatives of autoimmune disease patients, and the
      development of two or more autoimmune rheumatic diseases in one patient, the so
      called overlap syndromes. The genetic and environmental factors that lead to
      these phenomena interact in a complex fashion and influence the distinct
      phenotypic characteristics of each patient. In a previous case series, we
      described 23 Mexican Mestizo patients with overlap syndromes. Interestingly,
      rhupus tends to develop sequentially while sclerodermatomyositis tends to appear
      simultaneously. The clinical course of the other overlap syndromes is rather
      aggressive, although clinical manifestations respond to standard treatment. The
      second and/or third disease appears while the first one is still active, even
      with adequate treatment. The distinct course of overlap syndromes may be
      partially explained by the interplay of environmental factors with genes that
      predispose to autoimmunity in general and to manifestations of specific diseases.
      The analyses of genes that will help understand the pathophysiology of these
      diseases include several MHC complex genes, cytokines, AIRE, and PDCD1 amongst
      others.

PMID- 16431334
TI  - Complement, natural antibodies, autoantibodies and tissue injury.
AB  - Activation of the classical complement pathway represents an effector mechanism
      of intestinal ischemia/reperfusion injury. Mice deficient in complement receptors
      1 and 2 fail to produce a component of the natural antibody repertoire that binds
      to ischemia-conditioned tissues and activate complement. In contrast, mice prone
      to autoimmunity display accelerated and enhanced tissue injury that results from
      the binding of autoantibodies to injured tissues. Our experiments demonstrate
      that naturally occurring antibodies and autoantibodies mediate tissue injury only
      after an organ has been subjected to a stressor such as ischemia.

PMID- 16431336
TI  - Premature atherosclerotic disease in systemic lupus erythematosus--role of
      inflammatory mechanisms.
AB  - Mounting evidence from a growing body of epidemiologic studies demonstrates that
      patients with systemic lupus erythematosus (SLE) are at increased risk for the
      development of premature cardiovascular disease (CVD). However, awareness of
      accelerated atherosclerosis in young SLE patients, albeit growing, is still
      limited, as documented by the brief case presented. Inflammation is thought to
      play an important role in both the pathogenesis of SLE, as well as
      atherosclerotic vascular disease. Inflammatory processes that are shared by SLE
      and atherosclerotic disease include immune complex deposition and fixation,
      autoantibody binding, complement activation and CD40-CD40 ligand interaction. By
      examining the inflammatory mechanisms in common between SLE and atherosclerotic
      disease, we can come to a better understanding of the pathophysiology of the
      accelerated atherosclerotic process seen in patients with SLE and can gain
      insights into developing and instituting preventative and treatment strategies.
      In this article, we present a case of a young woman with SLE who presents with
      chest pain, followed by a review of inflammation-based pathogenic mechanisms that
      are shared by SLE and atherosclerotic cardiovascular disease.

PMID- 16431335
TI  - Difference in adhesion molecule expression (ICAM-1 and VCAM-1) in juvenile and
      adult dermatomyositis, polymyositis and inclusion body myositis.
AB  - To assess the differential expression of adhesion molecules ICAM-1 and VCAM-1 in
      vessels and muscle fibers in acquired inflammatory myopathy, a series comprising
      thirty-seven muscle biopsy specimens from patients with JDM, fifteen with DM,
      fifteen with PM and seven with IBM was studied. Histochemical and
      immunohistochemical tests (StreptABCcomplex/HRP) for ICAM-1 and VCAM-1
      (Dakopatts) were performed in serial frozen sections. ICAM-1 expression in
      vessels was significantly (p<0.0001) more present in JDM than PM, DM or IBM.
      However, in muscle fibers, ICAM-1 expression was absent in both JDM and IBM, but
      present in 33.4% and 40% in PM and DM respectively (p<0.0001). VCAM-1 expression
      in vessels was significantly more present in PM and DM than JDM and IBM
      (p<0.0001) while VCAM-1 expression in muscle fibers was almost absent in the four
      groups (p=0.2632). These findings emphasize the importance of adhesion molecules
      in the pathophysiology of the inflammatory myopathies, mainly the marked ICAM-1
      expression in vessels in JDM, corroborating the microvascular involvement in this
      disease. In contrast, VCAM-1 seems not to play a major role in JDM, as previously
      described in PM, DM and IBM. Adhesion molecule expression in JDM presents a
      differential characteristic when compared to PM, DM and IBM.

PMID- 16431337
TI  - NFAT transcription factors--new players in the pathogenesis of inflammatory
      arthropathies?
AB  - Inflammatory arthropathies are characterized by major changes in gene expression,
      which-ultimately-result from differential activities of intracellular signaling
      pathways and their associated inducible transcription factors. The nuclear factor
      of activated T cells' (NFAT) family of transcription factors plays diverse roles
      in a variety of processes in the immune system and other tissues. Preliminary
      evidence has recently emerged implicating NFAT family members directly in the
      pathogenesis of inflammatory arthropathies. Specific anti-NFAT drug therapy may
      add to the pharmacologic armamentarium against rheumatoid arthritis, other
      inflammatory arthropathies, and related autoimmune disorders.

PMID- 16431338
TI  - Pulse steroids: how much is enough?
AB  - High dose pulse intravenous steroids with 1 g of methylprednisolone (MEP) given
      daily, usually for three days, is an accepted practice to treat severe
      manifestations of systemic lupus erythematosus (SLE) or systemic vasculitides,
      despite the lack of definitive data. Most studies addressing the efficacy of high
      dose glucocorticoids (GCs) have been uncontrolled, retrospective or did not
      compare different doses. A limited number of studies comparing different doses of
      GCs suggest that lower doses of MEP given as intravenous pulse therapy might be
      as effective as the very high doses currently used. In addition, while early
      reports did not find serious adverse effects related to very high doses of
      steroids, several more recent studies indicate a high risk of serious infections
      proportional to the current or cumulative dose of GCs. While we await more
      conclusive studies addressing these questions, one might wonder whether we could
      be using too much of a good thing.

PMID- 16431339
TI  - Vitamin D deficiency in systemic lupus erythematosus.
AB  - Evidence from animal models and prospective studies of RA, multiple sclerosis,
      and type-1 diabetes suggest an important role for vitamin D as a modifiable
      environmental factor in autoimmune disease. This role has not been well studied
      in human SLE. We compared serum 25-hydroxyvitamin D (25(OH)D) levels between
      recently diagnosed SLE cases and matched controls, and examined disease
      characteristics in relationship to 25(OH)D among cases. Data from a population
      based cohort of 123 recently diagnosed SLE patients and 240 controls were used.
      We found a trend toward lower 25(OH)D levels in cases compared to controls, which
      was statistically significant in Caucasians (p=0.04), controlling for age, sex,
      season, and smoking. Overall, 67% of the subjects were vitamin D deficient, with
      mean levels significantly lower among African Americans (15.9 ng/ml) compared to
      Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found
      in 22 of the SLE cases, with presence of renal disease being the strongest
      predictor (OR 13.3, p<0.01) followed by photosensitivity (OR 12.9, p<0.01). These
      results suggest vitamin D deficiency as a possible risk factor for SLE and
      provide guidance for future studies looking at a potential role of vitamin D in
      the prevention and/or treatment of SLE.

PMID- 16431340
TI  - Transcriptional repression of interleukin-2 in human systemic lupus
      erythematosus.
AB  - T cells from patients with SLE produce decreased amounts of interleukin-2 (IL-2),
      a central cytokine in the regulation of the immune response. We discuss herein
      the abnormalities underlying IL-2 deficiency in SLE T cells.

PMID- 16431341
TI  - Targeted therapy for systemic sclerosis.
AB  - Systemic sclerosis is a multisystem disease whose therapy is focused at
      pathogenic pathways causing variable types of damage in the individual organs.
      There are 3 major pathways that cause organ damage in scleroderma. First, t
      cells, cytokines and inflammation are prominent very early in the disease. Early
      alveolitis which occurs before interestial fibrosis in the lungs is the best
      example of inflammation. Second, endothelial cell damage causes severe thickening
      of vessels and two of the most deadly complications in scleroderma, pulmonary
      arterial hypertension and renal crisis. Scleroderma renal crisis is now very
      treatable with angiotensin converting enzyme inhibitors. There are now treatments
      for pulmonary arterial hypertension which should improve outcome in these
      patients as well. Third, fibroblasts lead to severe cutaneous fibrosis or skin
      thickening that is the hallmark of the disease. No treatment is available but we
      are hopeful that new antagonists to the cytokine, TGF beta, will prove helpful. B
      cells and autoantibodies are not involved in the pathogenesis of the disease, but
      there are scleroderma specific antibodies that help in defining patient subsets.
      All of these factors are influenced by unknown inciting agents and the permissive
      genetic background.

PMID- 16431342
TI  - Digital ulcers in patients with systemic sclerosis.
AB  - Digital ulcers (DU), defined as necrotic lesions located at distal digits or
      overlying bony prominences, occur in up to 50% of patients with limited or
      diffuse systemic sclerosis (SSc). These lesions are extremely painful and lead to
      substantial functional disability. The pathogenesis of DU differs depending on
      their location. DU located at distal aspects of digits are thought to be related
      to tissue ischemia from several processes, including vasospasm secondary to
      Raynaud's phenomenon, intimal fibro-proliferation, and thrombosis of digital
      arteries. DU located over bony prominences, such as the phalangeal joints and
      elbows, are thought to be due to repetitive microtrauma and difficulty healing
      due to atrophic, avascular tissue overlying the joints. Management of DU include
      non-pharmacologic and pharmacologic modalities. This review summarizes the
      current available and investigational therapies for the treatment and prevention
      of DU in patients with SSc.

PMID- 16431343
TI  - S100A4 (Mts1): is there any relation to the pathogenesis of rheumatoid arthritis?
AB  - S100A4 (Mts1) belongs to the S100 family of calcium binding proteins, which are
      involved in diverse biological regulatory activities. An association between
      S100A4 and tumor progression has been demonstrated in several studies. S100A4
      binds to distinct intracellular target proteins and regulates specific functions
      involved in tumor progression such as cell motility, proliferation and apoptosis
      as well as remodelling of the extracellular matrix. Once released from the tumor
      or tumor-activated stromal cells, it may influence certain functions of target
      cells towards a more aggressive phenotype. Extracellular S100A4 has been
      demonstrated to contribute to angiogenesis and the increased production of matrix
      degrading enzymes by both endothelial and tumor cells. Moreover, S100A4 might be
      responsible for TCRgammadelta T-cell mediated lysis and negative regulation of
      matrix mineralization. Increased expression of S100A4 mRNA has recently been
      found in proliferating rheumatoid arthritis synovial fibroblasts and synovial
      tissues from rheumatoid arthritis patients. Synovial hyperplasia in rheumatoid
      arthritis consists of inflammatory cells and activated synovial lining cells
      which contribute to the progressive destruction of the joints during the disease.
      Since several phenomena are similar between rheumatoid arthritis and malignant
      tumors it can be hypothesized that S100A4 contributes to the invasive and tumor
      like behavior of rheumatoid arthritis synovium.

PMID- 16431344
TI  - A short review of the pathogenesis of Sjogren's syndrome.
AB  - Sjogren's syndrome can present in a heterogeneous manner with symptoms varying
      from systemic features such as unexplained fever, weight loss and neurological
      manifestations to the more typical symptoms of dry mucus membranes. There is
      discussion of the wide differential diagnosis, followed by a brief overview of
      the diagnosis, extraglandular manifestations and pathogenesis of primary
      Sjogren's syndrome.

PMID- 16431345
TI  - Aging of the immune system: a risk factor for autoimmunity?
AB  - Aging of the immune system, or immunosenescence, is characterized by changes in T
      cell subsets, cellular and molecular level alterations and thymic atrophy,
      resulting in a decline of T and B cell function. These alterations have been
      shown to be accompanied by a loss of ability to recognize "self" and "foreign"
      antigens. Therefore the development of autoimmune responses like production of
      autoantibodies has been hypothesized to be secondary to thymus involution with a
      decline of naive T cells and accumulation of clonal T cells with activation due
      to "neoantigens" during the aging process. Altered apoptosis and altered T cell
      homeostasis have been emphasized to promote a chronic inflammatory state and lead
      to the concept of a immune-risk phenotype. However, it has to be proven which
      kinds of mechanisms turn the immune system to manifest autoimmune disease and how
      speculated defects in T cell differentiation and interaction leading to premature
      aging of the immune system may contribute to the development of autoimmune
      diseases.

PMID- 16431346
TI  - BiP regulates autoimmune inflammation and tissue damage.
AB  - The endoplasmic reticulum chaperone BiP, in addition to its many important
      intracellular functions, has anti-inflammatory and immunomodulatory properties
      when present in the extracellular environment by the stimulation of an anti
      inflammatory gene programme from human monocytes and by the development of T
      cells that secrete regulatory cytokines such as interleukin-10 and interleukin-4.
      It can both prevent as well as treat ongoing collagen-induced arthritis. It is,
      therefore, a potential new biologic therapy for rheumatoid arthritis.

PMID- 16431347
TI  - Attempt to correct abnormal signal transduction in T lymphocytes from systemic
      lupus erythematosus patients.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease, which predominantly
      affects females, and causes multiple organ dysfunctions. Recent studies have
      revealed the underlying immunological abnormalities, especially in lymphocytes
      from SLE patients. T lymphocytes from SLE patients present abnormalities in T
      cell receptor (TCR) signaling, for example, decreased expression of TCR zeta
      chain, PKC theta, and NF-kB p65, decreased PKC dependent protein phosphorylation,
      impaired translocation of NF-kB p65, decreased production of IL-2 etc. Recently,
      it is known that reconstitution of deficient TCR zeta chain in T lymphocytes from
      SLE patients leads to restoration of impaired IL-2 production upon CD3/CD28
      stimulation. This time, analysis of abnormal TCR signaling in SLE patients and
      attempt to correct the impaired IL-2 production by replenishing missing signaling
      molecules are to be discussed.

PMID- 16431349
TI  - Developing the concept of adoptive cellular gene therapy of rheumatoid arthritis.
AB  - Progressive destruction of articular cartilage and bone is the pivotal problem of
      rheumatoid arthritis (RA). Joint destruction is the cause of severe disability
      and determines the long-term outcome of disease. Conventional therapy does not
      control this destructive process sufficiently and the anti-rheumatic drugs
      available today can cause severe systemic adverse effects. Local application of
      chondroprotective and osteoprotective agents by means of gene therapy would be an
      attractive alternative to conventional therapy of RA and could provide long-term
      expression of the therapeutic agents and minimize systemic adverse effects. For
      this purpose, we have developed the concept of adoptive cellular gene therapy.
      This treatment strategy is based on using genetically engineered cells that home
      specifically to sites of autoimmune inflammation and thus allow local delivery of
      therapeutic gene products. Ex vivo transduction of these cells avoids systemic
      exposure of the host to the transgene-encoding vector and thus adds to the safety
      of this approach. In this article of the CIS Spring School in Autoimmune Diseases
      2005 proceedings, we review our work on developing the strategy of adoptive
      cellular gene therapy and summarize recent advances in the evaluation of
      therapeutic effects and the identification of novel therapeutic targets.

PMID- 16431348
TI  - Disruption of immunological tolerance: role of AIRE gene in autoimmunity.
AB  - The mechanism underlying the generation of T and B autoreactive clones in
      autoimmune diseases is still unknown. Among genetic factors implicated in
      autoimmunity, Autoimmune Regulator gene (AIRE) is one of the candidates to better
      understand the complex scenario of autoimmune manifestations. AIRE mutations are
      responsible for the development of autoimmune polyendocrinopathy candidiasis
      ectodermal dystrophy (APECED) with monogenic autosomal recessive inheritance; it
      has been shown that AIRE regulates the negative selection of autoreactive T cells
      clones, driving the transcription of tissue-specific antigens in thymic
      epithelial cells. In various autoimmune manifestations correlated or not to
      APECED, AIRE variants act in a semidominant manner, leading to a reduction in
      AIRE protein amount per cell, and consequently to a marked decrease in ectopic
      proteins expression in the thymus. The co-occurrence of autoimmune diseases in
      the same individual has prompted several studies aimed to recognize shared patho
      physiological mechanisms; in this scenario small reductions in function could
      explain the predisposition to autoimmunity in AIRE-heterozygous carriers of
      missense mutations; further studies to investigate whether the AIRE gene is
      involved in determining these autoimmune manifestations should be carried out.

PMID- 16431350
TI  - Intravenous immunoglobulin for immunomodulation of systemic lupus erythematosus.
AB  - Intravenous immunoglobulin (IVIg) is used for replacement therapy in
      immunodeficiency states and for immunomodulation of various autoimmune diseases.
      Several case reports and series support a beneficial role of IVIg in systemic
      lupus erythematosus (SLE), both as salvage immunotherapy and in control of
      disease activity in general and amelioration of classical disease manifestations.
      Further, lupus nephritis can also be treated usually successfully with IVIg. A
      few questions remain unanswered as to the appropriate therapeutic dosage and the
      clinical manifestations that can be best treated with IVIg.

PMID- 16431351
TI  - Inflammatory and autoimmune complications of common variable immune deficiency.
AB  - Common variable immune deficiency (CVID) is associated with autoimmune and
      inflammatory complications in addition to recurrent infections. The most common
      conditions are idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia,
      sarcoid-like granulomatous disease and gastrointestinal inflammation. IVIG
      administration reduces the frequency of infections, but does not always prevent
      autoimmunity or inflammation. TNF antagonists and anti-CD20 immunomodulators have
      shown some efficacy in CVID in a few patients; further controlled studies are
      needed to determine the best management of these conditions in the setting of
      immunodeficiency.

PMID- 16431352
TI  - Toxic epidermal necrolysis in systemic lupus erythematosus.
AB  - Toxic epidermal necrolysis (TEN) is an acute, rapidly evolving mucocutaneous
      reaction with a high mortality rate characterized by extensive painful cutaneous
      and mucosal exfoliation and systemic involvement that is frequently associated
      with medication use. The treatment of this condition is controversial. Systemic
      lupus erythematosus (SLE) is a generalized autoimmune disease of unknown etiology
      characterized by the production of autoantibodies to self antigens. Several case
      reports in the literature have demonstrated an association between SLE and TEN,
      and it has been postulated that lupus-associated TEN may exist. In this review,
      we will explore the association of SLE and TEN, and its diagnosis and treatment.

PMID- 16431353
TI  - Fiddler crabs.

PMID- 16431354
TI  - U-turns on ant pheromone trails.

PMID- 16431355
TI  - Viagra slows the visual response to flicker.

PMID- 16431356
TI  - AAA+ molecular machines: firing on all cylinders.

PMID- 16431357
TI  - Insect navigation: no map at the end of the trail?

PMID- 16431359
TI  - Plastid origin: replaying the tape.

PMID- 16431358
TI  - Tubulogenesis: an inside job.

PMID- 16431360
TI  - Plant meristems: what you see is what you get?

PMID- 16431361
TI  - Honeybee vision: in good shape for shape recognition.

PMID- 16431362
TI  - Plastid division: the squeezing gets tense.

PMID- 16431363
TI  - Wnt signaling: a shaggy dogma tale.

PMID- 16431364
TI  - A heterochromatin barrier partitions the fission yeast centromere into discrete
      chromatin domains.
AB  - BACKGROUND: Centromeres are cis-acting chromosomal domains that direct
      kinetochore formation, enabling faithful chromosome segregation. Centromeric
      regions of higher eukaryotes are structurally complex, consisting of various
      epigenetically modified chromatin types including specialized chromatin at the
      kinetochore itself, pericentromeric heterochromatin, and flanking euchromatin.
      Although the features necessary for the establishment and maintenance of discrete
      chromatin domains remain poorly understood, two models have been proposed based
      either on the passive convergence of competing activities involved in individual
      domain formation or, alternatively, on the action of specific genomic sequences
      and associated proteins to actively block the propagation of one chromatin type
      into another. RESULTS: Functional analysis of centromeric sequences located at
      the intersection of Schizosaccharomyces pombe central core chromatin and outer
      repeat heterochromatin identified a chromatin barrier that contains a transfer
      RNA (tRNA) gene. Deletion or modification of the barrier sequences result in the
      propagation of pericentromeric heterochromatin beyond its normal boundary. The
      tRNA gene is transcriptionally active, and barrier activity requires sequences
      necessary for RNA polymerase III transcription. Moreover, absence of the barrier
      results in abnormal meiotic chromosome segregation. CONCLUSIONS: The
      identification of DNA sequences with chromatin barrier activity at the fission
      yeast centromere provides a model for establishment of centromeric chromatin
      domains in higher eukaryotes.

PMID- 16431366
TI  - Regulated and polarized PtdIns(3,4,5)P3 accumulation is essential for apical
      membrane morphogenesis in photoreceptor epithelial cells.
AB  - BACKGROUND: In a specialized epithelial cell such as the Drosophila
      photoreceptor, a conserved set of proteins is essential for the establishment of
      polarity, its maintenance, or both--in Drosophila, these proteins include the
      apical factors Bazooka, D-atypical protein kinase C, and D-Par6 together with D
      Ecadherin. However, little is known about the mechanisms by which such apical
      factors might regulate the differentiation of the apical membrane into functional
      domains such as an apical-most stack of microvilli or more lateral sub-apical
      membrane. RESULTS: We show that in photoreceptors Bazooka (D-Par3) recruits the
      tumor suppressor lipid phosphatase PTEN to developing cell-cell junctions (Zonula
      Adherens, za). za-localized PTEN controls the spatially restricted accumulation
      of optimum levels of the lipid PtdIns(3,4,5)P3 within the apical membrane domain.
      This in turn finely tunes activation of Akt1, a process essential for proper
      morphogenesis of the light-gathering organelle, consisting of a stack of F-actin
      rich microvilli within the apical membrane. CONCLUSIONS: Spatially localized
      PtdIns(3,4,5)P3 mediates directional sensing during neutrophil and Dictyostelium
      chemotaxis. We conclude that a conserved mechanism also operates during
      photoreceptor epithelial cell morphogenesis in order to achieve normal
      differentiation of the apical membrane.

PMID- 16431365
TI  - A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure
      and trafficking of epidermal growth factor receptor.
AB  - BACKGROUND: Arf GAPs are multidomain proteins that function in membrane traffic
      by inactivating the GTP binding protein Arf1. Numerous Arf GAPs contain a BAR
      domain, a protein structural element that contributes to membrane traffic by
      either inducing or sensing membrane curvature. We have examined the role of a
      putative BAR domain in the function of the Arf GAP ASAP1. RESULTS: ASAP1's N
      terminus, containing the putative BAR domain together with a PH domain, dimerized
      to form an extended structure that bound to large unilamellar vesicles containing
      acidic phospholipids, properties that define a BAR domain. A recombinant protein
      containing the BAR domain of ASAP1, together with the PH and Arf GAP domains,
      efficiently bent the surface of large unilamellar vesicles, resulting in the
      formation of tubular structures. This activity was regulated by Arf1*GTP binding
      to the Arf GAP domain. In vivo, the tubular structures induced by ASAP1 mutants
      contained epidermal growth factor receptor (EGFR) and Rab11, and ASAP1
      colocalized in tubular structures with EGFR during recycling of receptor.
      Expression of ASAP1 accelerated EGFR trafficking and slowed cell spreading. An
      ASAP1 mutant lacking the BAR domain had no effect. CONCLUSIONS: The N-terminal
      BAR domain of ASAP1 mediates membrane bending and is necessary for ASAP1
      function. The Arf dependence of the bending activity is consistent with ASAP1
      functioning as an Arf effector.

PMID- 16431367
TI  - Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a
      component of the multivesicular body-sorting machinery.
AB  - AMSH is an endosomal ubiquitin isopeptidase that can limit EGF receptor
      downregulation . It directly binds to the SH3 domain of STAM, which is
      constitutively associated with Hrs, a component of clathrin-coated structures on
      endosomes. This clathrin coat has been implicated in the recruitment of
      ubiquitinated growth factor receptors prior to their incorporation into internal
      vesicles of the multivesicular body (MVB) , through the concerted action of ESCRT
      complexes I, II, and III . We now show that AMSH is embedded within a network of
      interactions with components of the MVB-sorting machinery. AMSH and STAM, like
      Hrs , both bind directly to clathrin. AMSH also interacts with mVps24/CHMP3, a
      component of ESCRT III complex, and this interaction is reinforced through
      simultaneous STAM binding. We have explored the effect of interacting components
      on the in vitro enzymatic activity of AMSH. The enzyme shows specificity for K63-
      over K48-linked polyubiquitin chains in vitro and is markedly stimulated by
      coincubation with STAM, indicating that activation of AMSH is coupled to its
      association with the MVB-sorting machinery. Other interacting factors do not
      directly stimulate AMSH but may serve to orient the enzyme with respect to
      substrates on the endosomal membrane.

PMID- 16431368
TI  - Comparison of gene expression in male and female mouse blastocysts revealed
      imprinting of the X-linked gene, Rhox5/Pem, at preimplantation stages.
AB  - Mammalian male preimplantation embryos develop more quickly than females . Using
      enhanced green fluorescent protein (EGFP)-tagged X chromosomes to identify the
      sex of the embryos, we compared gene expression patterns between male and female
      mouse blastocysts by DNA microarray. We detected nearly 600 genes with
      statistically significant sex-linked expression; most differed by 2-fold or less.
      Of 11 genes showing greater than 2.5-fold differences, four were expressed
      exclusively or nearly exclusively sex dependently. Two genes (Dby and Eif2s3y)
      were mapped to the Y chromosome and were expressed in male blastocysts. The
      remaining two (Rhox5/Pem and Xist) were mapped to the X chromosome and were
      predominantly expressed in female blastocysts. Moreover, Rhox5/Pem was expressed
      predominantly from the paternally inherited X chromosome, indicating sex
      differences in early epigenetic gene regulation.

PMID- 16431369
TI  - Secretory cargo regulates the turnover of COPII subunits at single ER exit sites.
AB  - The COPII coat complex mediates the formation of transport carriers at
      specialized sites of the endoplasmic reticulum (ERES). It consists of the Sar1p
      GTPase and the Sec23/24p and the Sec13/31p subcomplexes . Both stimulate the
      GTPase activity of Sar1p , which itself triggers coat disassembly. This built-in
      GAP activity makes the COPII complex in principle unstable and raises the
      question of how sufficient stability required for cargo capture and carrier
      formation is achieved. To address this, we analyzed COPII turnover at single ERES
      in living cells. The half times for Sar1p, Sec23p, and Sec24p turnover are 1.1,
      3.7, and 3.9 s, respectively. Decreasing the amount of transport-competent cargo
      in the endoplasmic reticulum accelerates turnover of the Sec23/24p and slows down
      that of Sar1p. A mathematical model of COPII membrane turnover that reproduces
      the experimental in vivo FRAP kinetics and is consistent with existing in vitro
      data predicts that Sec23/24p remains membrane associated even after GTP
      hydrolysis by Sar1p for a duration that is strongly increased by the presence of
      cargo. We conclude that secretory cargo retains the COPII complex on membranes,
      after Sar1p release has occurred, and prevents premature disassembly of COPII
      during cargo sorting and transport carrier formation.

PMID- 16431370
TI  - Septate-junction-dependent luminal deposition of chitin deacetylases restricts
      tube elongation in the Drosophila trachea.
AB  - The function of tubular epithelial organs like the kidney and lung is critically
      dependent on the length and diameter of their constituting branches. Genetic
      analysis of tube size control during Drosophila tracheal development has revealed
      that epithelial septate junction (SJ) components and the dynamic chitinous
      luminal matrix coordinate tube growth. However, the underlying molecular
      mechanisms controlling tube expansion so far remained elusive. Here, we present
      the analysis of two luminal chitin binding proteins with predicted polysaccharide
      deacetylase activities (ChLDs). ChLDs are required to assemble the cable-like
      extracellular matrix (ECM) and restrict tracheal tube elongation. Overexpression
      of native, but not of mutated, ChLD versions also interferes with the structural
      integrity of the intraluminal ECM and causes aberrant tube elongation. Whereas
      ChLD mutants have normal SJ structure and function, the luminal deposition of the
      ChLD requires intact cellular SJs. This identifies a new molecular function for
      SJs in the apical secretion of ChLD and positions ChLD downstream of the SJs in
      tube length control. The deposition of the chitin luminal matrix first promotes
      and coordinates radial tube expansion. We propose that the subsequent structural
      modification of chitin by chitin binding deacetylases selectively instructs the
      termination of tube elongation to the underlying epithelium.

PMID- 16431371
TI  - serpentine and vermiform encode matrix proteins with chitin binding and
      deacetylation domains that limit tracheal tube length in Drosophila.
AB  - Many organs contain epithelial tubes that transport gases or liquids . Proper
      tube size and shape is crucial for organ function, but the mechanisms controlling
      tube diameter and length are poorly understood. Recent studies of tracheal
      (respiratory) tube morphogenesis in Drosophila show that chitin synthesis genes
      produce an expanding chitin cylinder in the apical (luminal) extracellular matrix
      (ECM) that coordinates the dilation of the surrounding epithelium . Here, we
      describe two genes involved in chitin modification, serpentine (serp) and
      vermiform (verm), mutations in which cause excessively long and tortuous tracheal
      tubes. The genes encode similar proteins with an LDL-receptor ligand binding
      motif and chitin binding and deacetylation domains. Both proteins are expressed
      and secreted during tube expansion and localize throughout the lumen in a chitin
      dependent manner. Unlike previously characterized chitin pathway genes, serp and
      verm are not required for chitin synthesis or secretion but rather for its normal
      fibrillar structure. The mutations also affect structural properties of another
      chitinous matrix, epidermal cuticle. Our work demonstrates that chitin and the
      matrix proteins Serp and Verm limit tube elongation, and it suggests that tube
      length is controlled independently of diameter by modulating physical properties
      of the chitin ECM, presumably by N-deacetylation of chitin and conversion to
      chitosan.

PMID- 16431372
TI  - The class I PITP giotto is required for Drosophila cytokinesis.
AB  - Phosphatidylinositol transfer proteins (PITPs) are highly conserved polypeptides
      that bind phosphatidylinositol or phosphatidylcholine monomers, facilitating
      their transfer from one membrane compartment to another . Although PITPs have
      been implicated in a variety of cellular functions, including lipid-mediated
      signaling and membrane trafficking, the precise biological roles of most PITPs
      remain to be elucidated . Here we show for the first time that a class I PITP is
      involved in cytokinesis. We found that giotto (gio), a Drosophila gene that
      encodes a class I PITP, serves an essential function required for both mitotic
      and meiotic cytokinesis. Neuroblasts and spermatocytes from gio mutants both
      assemble regular actomyosin rings. However, these rings fail to constrict to
      completion, leading to cytokinesis failures. Moreover, gio mutations cause an
      abnormal accumulation of Golgi-derived vesicles at the equator of spermatocyte
      telophases, suggesting that Gio is implicated in membrane-vesicle fusion.
      Consistent with these results, we found that Gio is enriched at the cleavage
      furrow, the ER, and the spindle envelope. We propose that Gio mediates transfer
      of lipid monomers from the ER to the equatorial membrane, causing a specific
      local enrichment in phosphatidylinositol. This change in membrane composition
      would ultimately facilitate vesicle fusion, allowing membrane addition to the
      furrow and/or targeted delivery of proteins required for cytokinesis.

PMID- 16431373
TI  - Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase
      delta.
AB  - Eukaryotic replication begins at origins and on the lagging strand with RNA
      primed DNA synthesis of a few nucleotides by polymerase alpha, which lacks
      proofreading activity. A polymerase switch then allows chain elongation by
      proofreading-proficient pol delta and pol epsilon. Pol delta and pol epsilon are
      essential, but their roles in replication are not yet completely defined . Here,
      we investigate their roles by using yeast pol alpha with a Leu868Met substitution
      . L868M pol alpha copies DNA in vitro with normal activity and processivity but
      with reduced fidelity. In vivo, the pol1-L868M allele confers a mutator
      phenotype. This mutator phenotype is strongly increased upon inactivation of the
      3' exonuclease of pol delta but not that of pol epsilon. Several nonexclusive
      explanations are considered, including the hypothesis that the 3' exonuclease of
      pol delta proofreads errors generated by pol alpha during initiation of Okazaki
      fragments. Given that eukaryotes encode specialized, proofreading-deficient
      polymerases with even lower fidelity than pol alpha, such intermolecular
      proofreading could be relevant to several DNA transactions that control genome
      stability.

PMID- 16431374
TI  - Inactivation of NADPH oxidase organizer 1 results in severe imbalance.
AB  - Otoconia are biominerals of the vestibular system that are indispensable for the
      perception of gravity. Despite their importance, the process of otoconia genesis
      is largely unknown. Reactive oxygen species (ROS) have been recognized for their
      toxic effects in antimicrobial host defense as well as in aging and
      carcinogenesis. Enzymes evolved for ROS production belong to the recently
      discovered NADPH oxidase (Nox) enzyme family . Here we show that the inactivation
      of a regulatory subunit, NADPH oxidase organizer 1 (Noxo1), resulted in the
      severe balance deficit seen in the spontaneous mutant "head slant" (hslt) mice
      whose phenotype was rescued by Noxo1 transgenes. Wild-type Noxo1 was expressed in
      the vestibular and cochlear epithelia and was required for ROS production by an
      oxidase complex. In contrast, the hslt mutation of Noxo1 was biochemically
      inactive and led to an arrest of otoconia genesis, characterized by a complete
      lack of calcium carbonate mineralization and an accumulation of otoconial
      protein, otoconin-90/95 (OC-90/95). These results suggest that ROS generated by a
      Noxo1-dependent vestibular oxidase are critical for otoconia formation and may be
      required for interactions among otoconial components. Noxo1 mutants implicate a
      constructive developmental role for ROS, in contrast to their previously
      described toxic effects.

PMID- 16431375
TI  - Cdc42 activation couples spindle positioning to first polar body formation in
      oocyte maturation.
AB  - During vertebrate egg maturation, cytokinesis initiates after one pole of the
      bipolar metaphase I spindle attaches to the oocyte cortex, resulting in the
      formation of a polar body and the mature egg. It is not known what signal couples
      the spindle pole positioning to polar body formation. We approached this question
      by drawing an analogy to mitotic exit in budding yeast, as asymmetric spindle
      attachment to the appropriate cortical region is the common regulatory cue. In
      budding yeast, the small G protein Cdc42 plays an important role in mitotic exit
      following the spindle pole attachment . We show here that inhibition of Cdc42
      activation blocks polar body formation. The oocytes initiate anaphase but fail to
      properly form and direct a contractile ring. Endogenous Cdc42 is activated at the
      spindle pole-cortical contact site immediately prior to polar body formation. The
      cortical Cdc42 activity zone, which directly overlays the spindle pole, is
      circumscribed by a cortical RhoA activity zone; the latter defines the
      cytokinetic contractile furrow . As the RhoA ring contracts during cytokinesis,
      the Cdc42 zone expands, maintaining its complementary relationship with the RhoA
      ring. Cdc42 signaling may thus be an evolutionarily conserved mechanism that
      couples spindle positioning to asymmetric cytokinesis.

PMID- 16431376
TI  - Haruan (Channa striatus) incorporated palm-oil creams : formulation and stability
      studies.
AB  - Topical emulsions stabilized with non-ionic emulsifiers have been an attractive
      alternative as vehicles for drug delivery, particularly for the patients
      suffering from dermatological problems. Haruan (a natural wound healer) creams
      were formulated with different types of emulsifiers (Tween 80 and Span 80) using
      different grades of Malaysian Palm-oleins (DFPL 56, 60, 62 and 65). The stability
      (at room temperature and accelerated stability testing) of the various creams was
      evaluated at different temperatures (5, 25 and 45 degrees C) for a period of 6
      months by measuring changes in droplet size, viscosity and percentage oil
      separation. The emulsifier type and concentration showed pronounced effect on the
      physicochemical properties of the cream, whereas storage time did not. This study
      suggested that the choice of emulsifiers and concentration of haruan extract are
      the most important factors in the stability of the haruan creams.

PMID- 16431377
TI  - Cyclic voltammetric study of alpha-methyldopa at carbon paste electrode.
AB  - The cyclic voltammetric behaviour of alpha-methyldopa at a silicon oil carbon
      paste electrode has been reported. This allowed the development of a quantitative
      method to determine alpha-methyldopa in LiCl, KCl, NaCl, HCl, H2SO4 and CH3COOH
      as supporting electrolytes. For qualitative characteristics, alpha-methyldopa
      showed an ECC mechanism in terms of electron transfer reaction (placing it in DPI
      zone) at carbon paste electrode. The values of transfer coefficients alpha and
      beta were determined. The larger DeltaEp values were obtained due to the use of
      unmodified carbon paste electrode (CPE) has decreased the rate of electron
      transfer at the surface of the test electrode. The first order rate constant
      values (ko) were within 0.10-7.78 +/- 0.1x10(-3) s(-1). Adsorption of analyte was
      also determined at CPE using repeated scan method.

PMID- 16431378
TI  - Pharmacokinetics of diclofenac sodium in normal man.
AB  - Diclofenac sodium was administered as 50 mg tablets to four healthy male
      volunteers in a two-way randomized crossover study in which volunteers were
      either fasted or were given a standard breakfast immediately prior to dosing.
      Blood samples were obtained upto 9 hours period and drug concentration were
      determined by HPLC method. Besides a significantly delayed (at p > 0.1) peak in
      fed state; an increase in absorption rate constant was observed as the only
      significant (at p > 0.05) effect of food on biopharmaceutic characteristic of
      diclofenac sodium. However, the intrinsic absorption of diclofenac sodium is also
      fast and it is not being the rate limiting factor in the bioavailability of
      diclofenac sodium, its decrease upto about 18 minutes (0.31 +/- 0.05 hr) from 11
      minutes (0.19 +/- 0.02 hr) produces a null difference as the net effect on
      bioavailability, particularly when the drug is to be used in multiple dosage
      regimen.

PMID- 16431379
TI  - Biopharmaceutical evaluation of oral tablet Atenolol (100 and 50 mg) on local
      population.
AB  - An open-label, randomized study was designed to determine the bioavailability
      (BA); pharmacokinetic (PK) and pharmacodynamic (PD) behaviour of Atenolol 50 mg
      (two pills) and 100 mg (one pill) tablet manufactured by a national
      pharmaceutical industry. Peak plasma concentration (Cmax): 1.33 +/- 0.31
      microg/ml, time to peak plasma concentration (Tmax): 2.2 +/- 0.27 hours, AUC
      (area under the plasma concentration-time curve) 6.34 +/- 2.1 microg-hr/ml for
      100 mg tab and Cmax: 1.07 +/- 0.23 microg/ml, Tmax: 2.5 +/- 0.35 hours, AUC 4.97
      +/- 1.09 microg-hr/ml for 50 mg (two pills) tab were observed. The BA and PK
      parameters such as Cmax, Tmax, are comparable to previous studies, although
      significant decrease in diastolic and systolic blood pressure (mmHg) upto a
      certain limit for a considerable duration was observed. However, relation between
      PK and PD may not be established due to regulatory biochemical feedback
      mechanism.

PMID- 16431380
TI  - Characterisation of oxidation products of Rauwolfia alkaloids.
AB  - The oxidation products of three Rauwolfia alkaloids having yohimbane skeleton,
      namely, reserpine, rescinnamine and ajmalicine have been characterised by
      chromatographic and spectroscopic techniques. The Rf values of the oxidation
      products (3, 4-dehydro derivatives) in several solvent systems and the spectral
      data on UV, IR, NMR and fluorescence characteristics have been determined to
      confirm the structure of these compounds.

PMID- 16431381
TI  - Synthesis and antibacterial activity of cephradine metal complexes : part II
      complexes with cobalt, copper, zinc and cadmium.
AB  - Cephradine, the first generation cephalosporin, is active against a wide range of
      Gram-positive and Gram-negative bacteria including penicillinase-producing
      Staphylococci. Since the presence of complexing ligand may affect the
      bioavailability of a metal in the blood or tissues, therefore, in order to study
      the probable interaction of cephradine with essential and trace elements present
      in human body, cephradine has been reacted with cobalt, copper, zinc and cadmium
      metal halides in L:M ratio of 2:1 in methanol and the products recrystallized
      from suitable solvents to pure crystals of consistent melting points. Infrared
      and ultraviolet studies of these complexes were carried out and compared with
      ligand. Magnetic susceptibility studies of these complexes were also carried out
      showing their paramagnetic behavior. From the infra red studies and elemental
      analysis of the complexes, it has been shown that the drug molecule serves as a
      bidentate ligand coordinating through both its carboxylate at C-3 and beta-lactam
      nitrogen and the metal having a square planar or octahedral geometry. To evaluate
      the changes in microbiological activity of cephradine after complexation,
      antibacterial studies were carried out by observing the changes in MIC (minimum
      inhibitory concentration) of the complexes and compared with the parent drug by
      measuring the zone of inhibition of complexes and compared with the parent
      cephalosporin against both Gram-positive and Gram-negative organisms. For MIC
      observation, serial dilution method was employed and zone series were determined
      by disk diffusion method. Our investigations reveal that formation of complexes
      results in decrease in antibacterial activity of cephradine and MIC values are
      increased.

PMID- 16431382
TI  - Competitive binding of ibuprofen and naproxen to bovine serum albumin : modified
      form of drug-drug displacement interaction at the binding site.
AB  - The competitive binding characteristics of ibuprofen and naproxen with respect to
      binding site on bovine serum albumin (BSA) was studied by equilibrium dialysis
      method at pH 7.4 and 25 degrees C. We studied the effect of one drug on the free
      concentration of another in vitro during concurrent administration. There was
      remarkable increase in free concentration of naproxen when ibuprofen (2x10(-5) M)
      was added to a 1:1 naproxen-BSA mixture (2x10(-5) M: 2x10(-5) M), suggesting that
      ibuprofen displaced naproxen from its binding sites. However free fraction of
      naproxen was not increased up to the level expected from direct competitive
      displacement. Free concentration of ibuprofen was hardly increased by naproxen
      when naproxen (2x10(-5) M) was added to the ibuprofen-BSA (1:1) mixture. But in
      both cases, in presence of ranitidine (site I specific probe), the free
      concentration of the displaced drug increased more prominently compared to that
      in absence of ranitidine. This result suggests that, ibuprofen displaces naproxen
      and vice versa from its high affinity binding site (site II) and the displaced
      drug rebounds to its low affinity binding site (site I) on BSA molecule. This
      form of modified displacement has been arbitrarily referred to as site-to-site
      displacement.

PMID- 16431383
TI  - Comparative study of different formulations of atenolol.
AB  - Tablets are the most common dosage form. Tablets can be prepared by dry method
      and wet methods, both methods have their own significance as well as
      disadvantages. Dry method and particularly direct compression is most simplest
      method of tablet manufacturing. On the other hand granulation is a multiple
      processing method which add complexity and make validation and control difficult.
      For comparative study of atenolol tablets a new formulation was designed and
      compressed by direct compression method. Then it's physical parameters including
      hardness, friability, diameter, thickness, disintegration time, dissolution test
      were performed and finally assay carried out for evaluation and characterization
      of this new formulation against other formulation available in the market.

PMID- 16431384
TI  - The effects of isoniazid (INH) on the hematocrit of the lizard, Uromastix
      hardwickii.
AB  - In recent years isoniazid has been used as an antituberculous chemophylactic
      agent. Severe adverse reactions have been reported following its extensive
      treatment. In addition to hepatic and neurologic disturbances, hematologic
      alterations have also been reported. Present study was conducted to determine the
      effect of 0.06 mg isoniazid on the lacertilian packed cell volume. It was 14.0
      per cent on day 5, 18.0 and 19.8 per cent on day 10 and day 15 respectively,
      whereas, it was 24.0, 24.2 and 24.6 per cent in controls on day 5, 10 and day 15
      respectively.

PMID- 16431385
TI  - Biosynthesis of bacitracin in solid-state fermentation by Bacillus licheniformis
      using defatted oil seed cakes as substrate.
AB  - Bacitracin is being imported in Pakistan involving substantial amount of foreign
      exchange for its incorporation in poultry feed. The cheap raw material for its
      production is readily available and cheap such as soybean meal, sunflower meal,
      wheat bran etc. Thus development of this technology in our country would result
      in saving a reasonable amount of foreign exchange by exploiting indigenous
      resources. The present study is concerned with the biosynthesis of antibiotic
      bacitracin in solid-state fermentation by Bacillus licheniformis on laboratory
      scale using defatted oil seed cakes of agricultural by-products as starting
      material for maximum production of the antibiotic Bacitracin. In solid-state
      fermentation, wheat bran, soybean meal, sunflower meal, rice hulls and their
      different combinations were used. The antibiotic activity, 48 hours after
      inoculation was 4375 i.u / gm when only soybean was used. However, maximum titre
      4820 i.u / gm of antibiotic was obtained using wheat bran and soybean meal in
      ratio of 1:3.

PMID- 16431387
TI  - Hypogylcemic activity of aqueous extract of some indigenous plants.
AB  - Pakistan is rich in medicinally important plants and has an ancient herbal
      treatment methods. Our work is based on the study of some indigenous plants which
      show inhibitory effect of glucose utilization, and are in use as hypoglycemic
      agent in traditional system of medicine. Gymnema sylvestre, Momordica charantia
      and Eugenia jumbolana have been shown to possess hypoglycemic activity of varying
      degree. The results in three different media revealed that, hypoglycemic activity
      is more prominent in neutral and basic media as compared to acidic medium.

PMID- 16431386
TI  - A new RP-HPLC method for analysis of meloxicam in tablets.
AB  - A simple and rapid high-performance liquid chromatographic (HPLC) method for the
      determination and quantification of meloxicam has been developed. The
      chromatographic system consisted of a Shimadzu LC-10 AT VP pump, SPD-10 AV VP UV/
      visible detector, and a CBM-102 Bus Module integrator. Separation was achieved on
      the micro Bondapak 125 A C18 10 microm column at room temperature. The sample was
      introduced through an injector valve with a 10 microl sample loop. Methanol:water
      (70:30 v/v) was used as mobile phase, with flow rate 2 ml/minutes. pH was
      adjusted to 2.6 with phosphoric acid. U.V detection was performed at 230 nm. The
      results obtained showed a good agreement with the declared content. Recovery
      values of meloxicam in tablets (in Melfax 15 mg tablets) were from 99.27 % to
      100.06 %. Piroxicam was used as an internal standard. The proposed method is
      rapid, accurate and selective; it may be used for the quantitative analysis of
      meloxicam from raw materials, in bulk drugs and other dosage formulations.

PMID- 16431388
TI  - A survey of multiple prescriptions dispensed in Saudi Arabia.
AB  - A study of out-patient prescriptions in King Fahad Hospital, Al-Baha, Saudi
      Arabia was undertaken. Prescribing patterns of 200 doctors were surveyed. For
      each doctor ten out-patient prescriptions were randomly selected for analysis
      during month of January 2000. The prescriptions were coded and analysed.
      Multivitamins and antibiotics were the drugs most frequently prescribed: a
      finding that suggests either a high degree of malnutrition and infectious disease
      or misuse of those drugs. Other commonly prescribed drugs are also discussed.

PMID- 16431389
TI  - Anti-bacterial alkaloids of Saracococca saligna.
AB  - The crude ethanolic extract of Saracococca saligna was found to be cytotoxic and
      antibacterial but produced no platelet aggregation induced by ADP. Antibacterial
      activity of two known alkaloid, pachyaximine-A and saracodine was determined.
      Pachyaximine-A possessed significant antibacterial activity against Escherichia
      coli, Staphylococcus aureus, Corynebacterium diphtheriae and Corynebacterium
      pyrogenes. Saracodme showed moderate activity against Staphylococcus pyrogenes,
      Escherichia coli, Staphylococcus aureus, Corynebacterium diphtheriae, Shigella
      boydii and Klebsiella pneumoniae.

PMID- 16431390
TI  - Electrolytes and sodium transport mechanism in diabetes mellitus.
AB  - The metabolic derangements and disturbances and their consequences in diabetes
      mellitus are well known more or less in details too. However, knowledge on the
      diabetic disorders in membrane functions and transport mechanisms is limited
      which is an essential factor in progression of the disease. Serum electrolytes
      were measured by flame photometer (Corning 410) and spectrophotometer (Spectro
      SC) in 60 diabetic patients with stable glycemic control (aged 38 +/- 2.5 years)
      and in 60 age-matched normal subjects with no known history of hyperglycemia as
      control. Erythrocytes were isolated from samples, washed and used for the
      estimation of sodium and potassium concentrations using flame photometer.
      Erythrocyte membranes were prepared for the estimation of Na+-K+-ATPase activity
      in terms of inorganic phosphate released/mg protein/hour. Na+-K+-ATPase activity,
      Intra-erythrocyte potassium and serum magnesium levels were significantly low in
      diabetic patients than in the controls. Serum and intra-erythrocyte sodium and
      serum potassium levels were increased significantly in patients as compared to
      control subjects. A significant effect of sex and interaction was observed on
      serum sodium, potassium and magnesium. A significant effect of sex, disease and
      interaction on red cell sodium, potassium and Na+-K+-ATPase activity was observed
      in male and female subjects. Na+-K+-ATPase dysfunction and changes in intra
      erythrocyte and serum sodium, potassium and magnesium induced by diabetes may be
      implicated in the pathogenesis of neuropathy, nephropathy and vascular diseases
      in humans. It is suggested that male diabetic patients are at high risk of
      diabetic complications than females.

PMID- 16431391
TI  - A new RP-HPLC method for analysis of mebeverine hydrochloride in raw materials
      and tablets.
AB  - A simple, sensitive, selective, reliable, least time consuming and rapid high
      performance liquid chromatographic method for the determination and
      quantification of mebeverine hydrochloride using hyoscine butylbromide as
      internal standard has been developed. The chromatographic system consisted of a
      Shimadzu LC-10 AT VP pump, SPD-10 AV VP UV visible detector, and a CBM-102 Bus
      Module integrator. Separation was achieved on the micro Bondapak 125 a C18
      10microm column at room temperature. The samples were introduced through an
      injector valve with a 10 microl sample loop. Acetonitrile-water (1:1 v/v) was
      used as mobile phase, with flow rate 1.7 ml/minutes. pH was adjusted to 2.9 with
      phosphoric acid. U.V detection was performed at 205 nm. The results obtained
      showed a good agreement with the declared content. Recovery values of mebeverine
      hydrochloride were from 99.80% to 100.13%. The proposed method is rapid,
      accurate, and selective and may be used for the quantitative analysis of
      mebeverine hydrochloride. The method was found to be specific, accurate, precise
      and reliable for the determination and quantification of mebeverine hydrochloride
      in form of raw materials, in bulk drugs and formulation. It was possible to
      determine all of them in the concentration range of 5-30 nano grams. The
      detection limit of mebeverine hydrochloride was 0.4-nano gram.

PMID- 16431392
TI  - The effects of mefenamic acid on the osmotic fragility of lacertilian
      erythrocytes.
AB  - Osmotic fragility of red cells is increased by the use of mefenamic acid. The use
      of this analgesic induces hemolytic anemia. Study of osmotic fragility of RBCs of
      control and test was observed following administration of 7.1 mg, 10.5 mg and 14
      mg/day mefenamic acid to each lizard. Increased osmotic fragility was observed
      with increase in the amount of dose on day 6 and day 12.

PMID- 16431393
TI  - Differential scanning calorimetry and surface morphology studies on coated
      pellets using aqueous dispersions.
AB  - The present study was conducted to examine the physicochemical changes during
      passage of drug through polymeric membranes and observe the surface morphology
      features of the coated pellets using scanning electron microscopy (SEM). Drug
      solution was first sprayed around inert pellets to form drug-layered pellets that
      were coated with two commercial aqueous dispersions namely, Eudragit NE30 and
      Kollicoat SR30 using bottom-spray fluidized bed technique. Differential scanning
      calorimetry (DSC) confirmed that no interactions existed between drug and
      polymers. Small peak of drug was observed in the DSC thermograms of Eudragit NE30
      coated pellets indicating that small amount of drug was still present in the
      polymeric membrane after dissolution. Views of SEM revealed as the coating levels
      of two types of aqueous dispersions were increased the surface of the pellets
      become more uniform and compact. Therefore, the diffusion length for dissolution
      medium to enter the drug layer and dissolved drug to diffuse out would be
      increased at higher coating levels. The polymer surface of coated pellets after
      12 hours dissolution testing seemed to be shrunk and size of the pellets were
      also reduced indicating the depletion of reservoir layer.

PMID- 16431394
TI  - Effects of tryptophan and valine administration on behavioral pharmacology of
      haloperidol.
AB  - Development of antipsychotics with slight/no extra-pyramidal symptoms (EPS)
      and/or other side effects is one of the exploring fields of drug research.
      Haloperidol is a high potency typical neuroleptic used in the treatment of
      schizophrenia but produces muscles related side effects commonly known as EPS.
      These effects are not produced following the administration of atypical
      neuroleptics such as clozapine. A severe side effect of clozapine treatment is
      however, agranulocytosis. This involves investigation on the mechanism by which a
      typical neuroleptic acting via serotonergic mechanism tends to produce less or no
      EPS. The present study was, therefore, designed to determine the effect of
      serotonin precursor tryptophan and a large neutral amino acid other than
      tryptophan (valine) on the modulation of haloperidol induced catalepsy and
      akinesia. Cataleptic effects of the drug and activity reducing effects were
      monitored on inclined surface and in an activity box or open field respectively.
      The results are discussed in the context of a role of tryptophan and valine
      induced changes of brain serotonin in modifying the extrapyramidal and
      monoaminergic effects of the typical neuroleptic haloperidol. In the present
      study administration of TRP and valine decreased activity in rats, haloperidol
      induced catalepsy' was not modulated by prior administration of tryptophan or
      valine. Brain serotonin levels were elevated by haloperidol treatment and
      correlated very well with the behavioral response. These findings suggest a
      possible serotonergic involvement in neuroleptic induced tardive dyskinesia and
      an amelioration of the disorder through TRP supplementation.

PMID- 16431395
TI  - Evaluation of ethylcellulose as matrices for controlled release drug delivery.
AB  - As the efficiency of a matrix forming polymer in sustaining drug release is a
      multiple function of physico-chemical nature of the active ingredient and pH of
      the surrounding environment, the study was undertaken to evaluate the effect of
      pH of dissolution media on the release profile of three drug molecules with
      diversified physico-chemical properties. Matrix tablets of diclofenac sodium,
      theophylline and diltiazem HCl were prepared using ethylcellulose as the matrix
      forming agent. The drug dissolution behavior of the matrix tablets were studied
      over 10 hours in buffer media of pH 1.2, 4.5 and 6.8. Elevation of pH of the
      dissolution medium increased the rate and extent of diclofenac release. However,
      for diltiazem HCl, increasing the pH showed the reverse pattern. Theophylline
      release, on the other hand, seemed to be unaffected by the pH of the dissolution
      media. This can be correlated with the physico-chemical characteristics of the
      drugs. Effect of compression force on drug release and tablet hardness was also
      studied. Increasing the compression force reduced drug release irrespective of
      the chemical nature of the drug molecule which can be attributed to the reduction
      of porosity and formation of continuous polymeric network within the matrix.
      Again, no significant change in tablet hardness was found with the increment of
      compression force. A near zero-order release kinetics were observed in all
      formulations investigated.

PMID- 16431396
TI  - Erythromycin synergism with essential and trace elements.
AB  - In order to establish the role of various essential and trace element
      complexation on the antibacterial activity of various macrolide antibiotics, the
      synergistic or antagonistic behavior of erythromycin metal complexes have been
      studied and compared with the parent drug. Metal complexes of erythromycin with
      magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and
      cadmium have been investigated for their antibacterial activity and compared with
      erythromycin by observing the changes in minimum inhibitory concentration (MIC)
      and by measuring the zone of inhibition of complexes against both Gram-negative
      and Gram-positive microorganisms. Various microorganisms used were Staphylococcus
      aureus, Enterococcus faecalis, Escherichia coli, Salmonella typhi, Proteus
      vulgaris, Shigella dysentery, Klebsiella pneumoniae and Staphylococcus
      epidermidis. For MIC observation, serial dilution method was employed and zone
      sizes were determined by diffusion disk method. Our investigations reveal that
      formation of erythromycin complexes result in synergistic effect i.e.,
      antimicrobial activity of complexes of erythromycin increases with respect to
      parent erythromycin drug and MIC of drug metal complexes decreased.

PMID- 16431397
TI  - Trace metals analysis in selected pharmaceutical multimineral formulations.
AB  - Twelve pharmaceutical multimineral formulations, marketed in Pakistan by various
      multinational and national pharmaceutical manufacturers were analyzed for
      calcium, copper, iron, magnesium, manganese, potassium and zinc contents using
      atomic absorption spectrophotometric (AAS) technique. Generally, the Ca, Fe, K
      and Mg contents were normal to higher range compared with the labeled quantity.
      The Cu, Mn and Zn contents were low in most of the formulations when compared
      with the labeled amounts. Potassium was quantified in some formulations where it
      was not labeled this may be due to the excepients that may have been used in the
      formulations. The high contents like iron, calcium may also be due to the
      contamination or excepients used in the preparation of these drugs.

PMID- 16431398
TI  - In vivo performance of controlled release pellets of diltiazem HCl.
AB  - The test formulation of controlled release diltiazem pellets was evaluated in
      vivo, in comparison with Herbesser SR. Six healthy volunteers participated in the
      study, conducted according to a randomized, two-way crossover study design. The
      preparations were compared using the pharmacokinetic parameters plasma
      concentration-time curve (AUC(0- infinity)), peak plasma concentration (Cmax) and
      time to reach maximum plasma concentration (Tmax) were estimated from the plasma
      concentration-time profiles for each volunteer. The test formulation was found to
      be comparable with the Herbesser SR in the extent of bioavailability but differ
      in the rate of absorption, the test formulation being less sustained. No lag time
      was observed in any of the volunteers indicating that both formulations started
      to release their drug content immediately upon rupture of the capsule but in
      sustained manner. Moreover, the values of pharmacokinetic parameters obtained
      were comparable to those reported in the literature.

PMID- 16431399
TI  - Colorimetric determination of indolic drugs.
AB  - A colorimetric method has been developed for the quantitative determination of
      the rescinnamine, reserpine upto (-10(-4M)), Yohimbine on complexation with
      bromothymol blue. The coloured complexes exhibit absorption maxima in the region
      415-416 nm. The RSD (Relative Standard Deviation) of the method is 2.02%. The
      method is simple, easy, rapid and convenient for routine analysis of the indolic
      drugs.

PMID- 16431400
TI  - Neurochemical estimations of some new quaternary phenacyl-bromopiperidinium
      compounds.
AB  - Considering the fact that N-alkyl substituted quaternary ammonium salts of
      piperidinium bromide induce brain catecholamine and indoleamine metabolism (Black
      et al., 1986), we thought it may be valuable to investigate the effects of three
      selected phenacyl derivatives (I, V and VIII) of piperidine on brain monoamines
      metabolism in mice (100mg/kg body weight) assuming that these derivatives might
      alter the brain indoleamine and catecholamine levels differently. Studies are
      carried out by using HPLC technique. It was found that compound VIII possessed
      greater neuroleptic activity as compared to compounds I and V.

PMID- 16431401
TI  - In vitro release of tetracyclines in presence of H2-receptor antagonists.
AB  - There are a number of drug interactions reported for tetracyclines with many
      other drugs. In present study in vitro release of five different tetracyclines
      i.e., tetracycline, demeclocycline, oxytetracycline, methacycline and doxycycline
      in presence of cimetidine and ranitidine has been studied by USP XX dissolution
      method. The release of almost all tetracyclines was depressed in presence of
      cimetidine and ranitidine while in some cases the value were greatly increased
      due to the formation of charge transfer complexes of the antibiotic with H2
      receptor antagonists, which gave absorbance at same wavelengths but with much
      higher molar absorptivity. An attempt was made to elucidate the mechanism of this
      effect.

PMID- 16431402
TI  - Prevalence rate of Down's syndrome in Karachi resident women.
AB  - Prevalence rate of Down's syndrome in one thousand women of Karachi were
      evaluated. The preliminary screening showed that 80 out of 1000 women fall in
      this category based on MSAFP. Further tests were augmented such as hCG, ME along
      with MSAFP confirmed that 0.2% patients delivered babies with Down's syndrome.

PMID- 16431403
TI  - Chemotaxonomic significance of guaiane sesquiterpenoids from Amoora rohituka.

PMID- 16431405
TI  - Port-access-assisted aortic valve replacement: a comparison of minimally invasive
      and conventional techniques.
AB  - BACKGROUND: A hybrid Port-Access (PA) approach to aortic valve surgery (MPAVR)
      was designed as a less invasive aortic valve operation. The approach combines
      components of Port-Access technology with conventional cardiac surgical
      techniques via a limited sternal incision. This technique is compared to
      conventional aortic vale replacement (CAVR) for safety and efficacy. METHODS: One
      hundred eighty patients had aortic valve surgery between January 1, 2000, and
      June 30, 2004. Fifty-eight patients (32%) had primary isolated aortic valve
      replacement, 22 of those 58 patients (38%) underwent MPAVR procedures consisting
      of a limited inverted-T sternotomy, direct aortic cannulation, a percutaneous PA
      endocoronary sinus cardioplegia catheter, an endovent pulmonary artery catheter,
      and a percutaneous femoral endovenous return catheter. Thirty-six patients (62%)
      had aortic valve replacement by sternotomy and standard cardiopulmonary bypass
      techniques. The MPAVR and CAVR groups were compared for demographics and
      intraoperative and postoperative outcomes. RESULTS: Age, obesity, diabetes, New
      York Heart Association classification, ejection fraction, and other patient
      characteristics were not significantly different between the groups. MPAVR
      patients had lower Society of Thoracic Surgery risk scores (3.1 versus 3.9; P =
      .277). MPAVR patients were more likely to receive a stentless valve (36% versus
      11%; P = .042) and required longer operative times (237 min versus 189 min; P
      <.001). Postoperative complications were minimal and equivalent. A single
      mortality in the CAVR group resulted in an overall mortality of 1.7%. CONCLUSION:
      This hybrid, less invasive PA-assisted approach to aortic valve surgery is safe
      and effective. A total sternotomy can be avoided in selected aortic valve
      patients. Results equivalent to CAVR can be expected with this minimal access
      operation.

PMID- 16431404
TI  - The progress of mitral regurgitation after isolated coronary artery bypass in
      cases of ischemic mitral regurgitation.
AB  - BACKGROUND: Mitral valve intervention combined with coronary artery bypass
      surgery is inevitable in the case of severe mitral regurgitation in patients with
      coronary artery disease because the prognosis is poor without mitral correction.
      The best treatment protocol for patients with a moderate degree of mitral
      regurgitation is under debate. To clarify the optimal management for these
      patients, we evaluated the progress of mitral regurgitation after isolated
      coronary artery bypass surgery in cases of ischemic mitral regurgitation.
      METHODS; The study was conducted between March 2001 and April 2003. Forty-seven
      patients (70% men, with a mean age of 61 years, a mean ejection fraction of
      43.7%, and a mean New York Heart Association class of 2.53) with preoperative
      diagnoses of moderate degree ischemic mitral regurgitation (Grade 3 mitral
      regurgitation on a scale of 0 to 4) and coronary artery disease, without leaflet
      pathology, underwent isolated coronary artery bypass surgery. Patients were
      followed-up at a mean of 22 months and an echocardiographic evaluation was done
      to determine the progress of the mitral disease. RESULTS: The 30-day operative
      mortality rate was 2.1%. In the postoperative period, the mean ejection fraction
      was 46.9% and the mean functional capacity of the patients was 1.31. Mitral
      regurgitation regressed to a mild degree in 56.9% of the patients. The 2-year
      survival rate was 93.7%. CONCLUSIONS: Patients with moderate ischemic mitral
      regurgitation and coronary artery disease who underwent coronary artery bypass
      surgery alone had acceptable results. We are of the opinion that isolated
      coronary artery bypass surgery might be a good treatment choice for moderate
      degree ischemic mitral regurgitation.

PMID- 16431406
TI  - Sensory and color characteristics of frozen ready-made sauces.
AB  - The paper presents the results of investigation of the replacement of imported
      emulsifiers, which are in use with plant protein products e.g. soybean isolate >>
      SUPRO 500 E << as well as the use of microbiologic preparation like brewery yeast
      in combination with maltodextrin, aiming to investigate the sensory and color
      characteristics of frozen ready-made sauces. Color characteristics of
      investigated samples were defined by photoelectric tristimulus colorimeter
      Minolta CR 300. Regarding the obtained values it can be concluded that no color
      change was estimated neither after preparation, nor after 180 days of frozen
      storage and microwave defrosting, depending on the composition of sauces and
      applied packaging. Freezing, storage, and microwave defrosting affect the change
      of certain sensory characteristics (layering and homogeneity), and this reffers
      to the second group of samples in the first place.

PMID- 16431407
TI  - Supercritical CO2 extraction of oilseeds: review of kinetic and equilibrium
      models.
AB  - Mass transfer models on supercritical carbon dioxide (SC-CO2) extraction of
      vegetable oils are reviewed, that may facilitate the scale-up of laboratory data
      for industrial design purposes. Reviewed mechanisms of oil transport within the
      solid matrix include the desorption from the solid, the formation of a shrinking
      core of condensed oil in a non-adsorbing porous matrix, and diffusion in a
      homogenous medium. Analyzed simplificat ions of a general mass transfer model
      include external control of mass transfer rates, internal control of mass
      transfer rates, consideration of a linear driving force, and steady state
      approximations, among others. More complex two-stage models, and critical
      comparisons of some of the proposed models are also included. Trends for the
      external mass transfer coefficient and effective diffusivity in the solid matrix
      from studies on SC-CO2 extraction of oil from vegetable substrates are thoroughly
      discussed and contrasted with those obtained using simpler model systems. The
      possible effect of the axial dispersion on the rate of extraction is also
      discussed. Finally, the high-pressure vegetable oil-CO2 phase equilibrium is
      discussed in connection with its influence on the mass transfer process. Special
      emphasis is given to the role of the solid matrix on high-pressure phase
      equilibrium.

PMID- 16431409
TI  - Astaxanthin: a review of its chemistry and applications.
AB  - Astaxanthin is a carotenoid widely used in salmonid and crustacean aquaculture to
      provide the pink color characteristic of that species. This application has been
      well documented for over two decades and is currently the major market driver for
      the pigment. Additionally, astaxanthin also plays a key role as an intermediary
      in reproductive processes. Synthetic astaxanthin dominates the world market but
      recent interest in natural sources of the pigment has increased substantially.
      Common sources of natural astaxanthin are the green algae Haematococcus
      pluvialis, the red yeast, Phaffia rhodozyma, as well as crustacean byproducts.
      Astaxanthin possesses an unusual antioxidant activity which has caused a surge in
      the nutraceutical market for the encapsulated product. Also, health benefits such
      as cardiovascular disease prevention, immune system boosting, bioactivity against
      Helycobacter pylori, and cataract prevention, have been associated with
      astaxanthin consumption. Research on the health benefits of astaxanthin is very
      recent and has mostly been performed in vitro or at the pre-clinical level with
      humans. This paper reviews the current available evidence regarding astaxanthin
      chemistry and its potential beneficial effects in humans.

PMID- 16431408
TI  - A review of the effects and mechanisms of polyphenolics in cancer.
AB  - This paper is a comprehensive review of the effects of bioactive polyphenolic
      compounds commonly found in many fruits and vegetables on cancer. These include
      the pheniolic acids, anthocyanins, catechins, stilbenes and several other
      flavonoids. We have attempted to compile information from most of the major
      studies in this area into one source. The review encompasses the occurrence and
      bioavailability of the polyphenolics, the in vitro and in vivo evidence for their
      effects on cancer, both positive and negative, and the various mechanisms by
      which the chemicals may exert their effects. Although most of the work done to
      date indicates a chemopreventative activity of these compounds, there are some
      studies that show cancer-inducing or no effects. There are several common
      mechanisms by which these chemicals exert their effects that could be conducive
      to additive, synergistic, or antagonistic interactions. These include effects on
      cellular differentiation, proliferation, and apoptosis, effects on proteins and
      enzymes that are involved in these processes at a molecular level, and other
      various effects through altered immune function and chemical metabolism.

PMID- 16431410
TI  - Low incidence of adverse events following 90-minute and 3-minute infusions of
      intravenous iron sucrose in children on erythropoietin.
AB  - AIM: To define the adverse events following two different rates and methods of
      intravenous iron sucrose infusions in children with anaemia due to chronic renal
      impairment. METHODS: Two prospective observational studies were undertaken to
      characterize the adverse events following iron sucrose administration in children
      with renal impairment and on erythropoietin. Between January 1999 and April 2003,
      5 mg/kg of intravenous (IV) iron sucrose was given over 90 min and repeated 24 h
      later. Between May 2003 and September 2004, in children with better venous
      access, a single dose of 2 mg/kg of IV iron sucrose was administered over 3 min
      during an outpatient clinic visit and haemodialysis sessions. Following
      infusions, children were monitored for immediate and delayed adverse events. All
      such events were documented and dealt with appropriately. Test doses were not
      used. RESULTS: A total of 870 infusions over 90 min were administered to 72
      children. Three children developed abdominal pain. One child developed worsening
      of hypertension (not related to iron sucrose). Sixty-five doses were administered
      over 3 min to 20 children, and six minor adverse events were documented.
      CONCLUSION: Although 90 min infusion is associated with fewer adverse events, no
      life-threatening events were documented in either method.

PMID- 16431411
TI  - Congenital systemic Langerhans cell histiocytosis presenting as hydrops fetalis.
AB  - Congenital Langerhans cell histiocytosis (LCH) encompasses a wide spectrum of
      disease involvement and severity. Congenital "self-healing" cutaneous LCH
      represents one end of the spectrum, whereas the case we encountered represents
      the other extreme. A rare case of congenital LCH with severe multiorgan
      involvement presenting as hydrops fetalis is described in this report. Hydrops
      fetalis has not previously been associated with congenital LCH. The overall
      clinical features of this infant closely mimicked those of disseminated
      congenital infection, and he ran a fulminant and rapidly fatal course.
      CONCLUSION: A high index of suspicion is required to diagnose congenital LCH in
      the early neonatal period. Hydrops fetalis is an ominous sign and probably
      reflects severe systemic disease compromising the well-being of the fetus.

PMID- 16431412
TI  - Polyarteritis nodosa presenting with a leg mass.
AB  - We report an unusual presentation of polyarteritis nodosa in a 2-y-old child. The
      child presented with a mass of the left leg adjacent to the calf, and the biopsy
      showed polyarteritis nodosa. Further investigations confirmed systemic features,
      and X-rays showed a periosteal reaction. CONCLUSION: Childhood polyarteritis
      nodosa may present with a lower limb inflammatory mass.

PMID- 16431548
TI  - Day-to-day weight changes in young men.
AB  - 1. Body weight changes from day-to-day have been recorded in 140 young soldiers.
      A total of 2087 weight changes were examined, and 32% of these represented
      changes of 0.5 kg or more; on 6.2% of all occasions the change was 1.0 kg or
      more. 2. There were significant correlations between change in body weight and
      food intake, and also with energy expenditure. Of the large weight changes (0.5
      kg or more) 11% were associated with days of exceptionally high or exceptionally
      low levels of activity; 7% were associated with days when food intake was
      unusually large or small. 3. On occasions when fluid intake and urine volume were
      measured, there was a significant correlation between fluid balance (fluid intake
      less urine volume) and weight change. 4. The weight of faeces varied from 75 to
      210 g. It is concluded that irregularity of defaecation can be only a minor cause
      of weight irregularity.

PMID- 16431549
TI  - Social class and marital distance in Oxford City.
AB  - A study has been made of social class distributions and their effects on marital
      movement in the city of Oxford from 1837 to the present day. The data have been
      obtained from the marriage registers of nine ecclesiastical parishes which
      transect the city. There is marked social class heterogeneity according to
      district, but when the data are combined some striking relationships between
      occupation and the distributions of marital distance emerge. In general distance
      decreases and amounts of city endogamy increase almost linearly as one moves from
      Class I to Class V. There appears to be, however, no very great increase in
      marital distance in this century as compared with the situation in the last two
      thirds of the nineteenth century. Some of the differences between the social
      classes are due to differences in marital age, but even after this has been taken
      into account there remains a very statistically significant relationship between
      class and marital movement.

PMID- 16431550
TI  - Interrelationships of skeletal maturation, sexual development and somatic growth
      in man.
AB  - Data on the age of attainment of various stages of puberty in some 70 girls and
      100 boys of the longitudinal Harpenden Growth Study have been used to study the
      relation between skeletal age and sexual maturation. The variation in the
      skeletal ages of girls when they attained breast stages 2 and 5, pubic hair stage
      3, the peak of adolescent growth spurt and 95% of their adult height was compared
      with the corresponding variation in their chronological ages. Only at menarche,
      95% mature height and pubic hair stage 3 was skeletal age significantly less
      variable than chronological age. In boys at 95% of their mature height, skeletal
      age was significantly less variable than chronological age but no significant
      differences were found at genital stages 2 or 5, pubic hair stage 3, or the peak
      of the adolescent growth spurt. There was a positive correlation between skeletal
      and chronological age on reaching each stage of puberty in both sexes. The data
      suggest that the ossification of the skeleton in prepubertal children is
      independent of those maturational processes which lead to the development of the
      secondary sex characters. The role of skeletal age in predicting adult height is
      apparently not dependent upon a relationship between skeletal age and the
      attainment of peak height velocity but upon a more direct relationship with the
      percentage of growth which has been completed.

PMID- 16431551
TI  - Notes on the statistics of growth standards.
AB  - The problems of constructing population standards for measurements such as height
      and age points such as menarche are discussed. Extreme centiles, such as the 3rd,
      estimated from a Gaussian distribution have a considerable imprecision, the
      amount of which is detailed. Non-parametric estimation, as usually used for
      weight, is compared with transformation to Gaussianity and thence parametric
      estimation. Regression standards are discussed, whereby the subject is compared
      with a relevant subsection of the population rather than all of it, and it is
      suggested that velocity of growth standards might be couched in these terms.

PMID- 16431552
TI  - The relationship of leg volume (muscle plus bone) to maximal aerobic power output
      on a bicycle ergometer: the effects of anaemia, malnutrition and physical
      activity.
AB  - The relationship of maximal power output (VO2 max) to leg muscle plus bone)
      volume (LV) has been analysed in African children suffering from malnutrition and
      severe anaemia and in a group of rural adult Africans engaged in prolonged,
      active daily work. The results are examined in relation to 'normal' healthy
      active (but not in training) African ? s and ? s aged 7-35 years. The analysis
      clearly demonstrates that the association between VO2 max and LV is not causal;
      the effects of increased habitual activity and anaemia show that the two
      parameters can be varied independently. The effect of habitual activity on the
      VO2 max : LV relationship is essentially additive, whereas the effect of anaemia
      is multiplicative. However in malnutrition, the relationship remains unchanged;
      VO2 max decreases paripassu with the reduced leg (muscle plus bone) volume. Iron
      therapy produces an increase in VO2 max) towards normal values without a
      concomitant change in LV. The results give a clearer understanding of the
      relationship between 'active' muscle mass and aerobic power output on the bicycle
      ergometer and could be used as a basis for clinical diagnosis in the industrial
      and medical fields, particularly for cases of debilitating disease which have an
      effect on physiological performance and effort intolerance. The data at present
      cannot be applied to men and women over 35 years of age.

PMID- 16431553
TI  - Twins: measures of birth size at different gestational ages.
AB  - Means, standard deviations, and empirical centile values are given for birth
      weight, length and head circumference for twins born at gestational ages 31+ to
      42+ weeks. The data are compared with recent results for singletons, and the
      twins show a deficit that becomes greater as gestational age increases. Although
      weight may be slightly more affected than the other two measures, the relative
      growth suppression for twins is quite similar in all three dimensions.
      Comparatively, the average size of twins born at 33+ weeks gestational age is
      equal to the 36th centile for singletons; but at 40+ weeks gestational age, the
      average size for twins is below the 5th centile for singletons.

PMID- 16431554
TI  - Caste variation in the distribution of placental alkaline phosphatase genes among
      the Hindus of West Bengal.
AB  - 798 placentas (Brahmin 141, Kayastha 303, Mahishya 91 and mixed low castes 263),
      from Calcutta hospitals, have been studied by starch gel electrophoresis for
      alkaline phosphatase types. The estimated gene-frequencies resemble those found
      else-where in caucasoid populations. Statistically significant differences (P
      approximately 0.02) were, however, noticed between the broadly divided upper
      caste group (Brahmin and Kayastha) and the lower caste group (Mahishya and mixed
      low castes) in respect of Plf 1 and Pls 1) gene distributions. The upper caste
      group has higher Plf 1 and lower Pls 1 frequencies than the lower caste group.
      The two broad caste groups are, however, quite uniform in Pli 1 distribution. All
      the six common phenotypes (S1, F1, I 1, S1F1, S1 I 1 and F1 I 1) and seven rare
      phenotypes (S1S2, S1S3, F1F2, F1S2, F2S1, F1S3 and I 1S2) were found.

PMID- 16431555
TI  - Arterial pressures in a general practice.
AB  - Systolic and diastolic readings of blood pressure were recorded for 5386 (2585
      males and 2801 females) members of a general practice situated in and around
      Ballycastle, County Antrim. Polynomials to predict blood pressure from age were
      derived for systolic and diastolic pressures of males and females. Polynomials to
      predict blood pressure variance from age were derived for both systolic and
      diastolic pressure of each sex. Age-sex adjusted diastolic and systolic scores
      were calculated for each of the 5386 members of the practice using a technique
      similar to that reported by Hamilton et al. (1954 a, b).Parent-child correlations
      ranging from -0.21 to 0.17 were observed; however, when all sibships were
      considered together irrespective of size coefficients which were significantly
      greater than zero generally involved the mother of the child. No sib-sib
      correlation (all sibship sizes combined), except those involving twins exceeded
      the value 0.13. Husband-wife correlations were similar to the corresponding
      parent-offspring correlations when both husband and wife were aged 45 years or
      more. Generally speaking, the coefficients found in this study were lower than
      those of other workers and reasons are discussed why the estimates of the present
      paper may not be unbiased.

PMID- 16431556
TI  - The seasonal rhythm of menarche in girls attending schools in Baghdad.
AB  - 1. The seasons and years of first menstrual period of 5000 girls aged 13-18
      years, attending schools in Baghdad, were investigated retrospectively. 2. There
      was a highly significant seasonal rhythm of menarche with the peak in summer
      (July) and lowest extreme in winter (December) and autumn (November). This rhythm
      was the same, irrespective of whether girls had their first menses recently or
      not, and whether they were early or late maturers. 3. No significant association
      was found between the month of birth and the month of menarche. 4. No significant
      influence of age at menarche on its seasonal distribution was found. 5. There was
      a close, though not exact, relation between the seasonal change in day length and
      the rhythm of menarche. 6. The incidence of conception showed a significant
      seasonal rhythm but not coincident with menarche; the lowest level was in spring
      rather than in autumn or winter, when the day length is shortest.

PMID- 16431557
TI  - Diurnal variation in stature and sitting height in 12-14-year-old boys.
AB  - 1. Measurements of stature and sitting height were made at 0930 and 1400 h on 19
      boys aged 12-14 years with the "stretching upward" technique. 11 different boys
      were similarly measured at 1000 and 1700 h. 2. The average decrease in stature
      from 0930 to 1400 h was 2.0 mm and from 1000 to 1700 h was 4.6 mm. The
      corresponding values for sitting height were 2.0 mm and 2.8 mm. 3. No strong
      evidence for individual differences in diurnal change was found. 4. The standard
      error of stature measurement, estimated from duplicate measurements taken five
      minutes apart by the same observer in the afternoon sessions, was +/- 1.8 mm.

PMID- 16431658
TI  - Climate and the weight/height relationship in sub-Saharan Africa.
AB  - 25 populations of the rain forest and 44 of the open country, all descended from
      the West-Central African stock which lived in the latter biome, are compared for
      body weight and height. On a log weight/height diagram, the 69 populations
      cluster along a straight line which intersects the lines of equal body
      weight/surface ratio: the shorter the body size, the lower the ratio tends to be.
      The rain forest populations are concentrated in the lower part of the bivariate
      distribution. The shortest one, the Mbuti Pygmies, has a very low ratio despite a
      relatively heavy weight. The shorter stature of the rain forest populations seems
      to be largely genetic in origin; it probably results from selective pressure
      exerted by the thermal stres in this hot and wet biome where sweating is of low
      thermolytic efficiency. The amount of reduction of adult stature depends for a
      large part on the number of generations spent in the forest by the population.
      Line A (in figure 1) is similar to a growth trend. The 69 populations differ
      genetically by the target that growth has to reach on a common log weight/height
      trend line. They achieve this differentiation through different speeds of growth.

PMID- 16431659
TI  - A new method for assessment of dental maturity using the individual curve of
      number of erupted permanent teeth.
AB  - A new method for the evaluation of dental age in healthy children, using the
      curve of the total number of erupted permanent teeth, is presented. The method is
      based on the observation that the curves of the total number of teeth erupted are
      parallel and similar in shape in different individuals provided that logarithms
      are used for both age and number of erupted teeth. The chronological age for a
      specific reference point on the eruption curve was determined graphically in
      individual subjects. At this age each child has reached the same degree of dental
      maturity. A group of 133 healthy boys and 137 girls was examined annually for
      seven years. The mean age at the reference point of the tooth eruption curve was
      8.75 years for the boys and 8.44 years for the girls.

PMID- 16431660
TI  - Water balance and body weight: studies in a tropical climate.
AB  - Total body weight, water balance and energy balance were estimated in young adult
      men in a hot climate, over three 6-day periods. The aim was to determine the
      relative contributions to body weight changes of fluctuations in water and energy
      stores. In these subjects, the small observed body weight changes were due almost
      entirely to water balance changes. Water balance was regulated to within +/- 1%
      of body weight from day-to-day.

PMID- 16431661
TI  - Differences between ethnic groups in sex dimorphism of adult height.
AB  - An analysis has been made of sex dimorphism in adult height using data from 58
      Negroid, 76 European, and 67 Amerindian populations. Regression analyses were
      carried out on the sex difference and sex average of male and female stature
      means. The greatest sex dimorphism was found in Amerindians and the least in
      Negroid populations. Data from 36 Asiatic and 27 New Guinea populations have also
      been considered. It seems that sex dimorphism in adult height has a strong
      genetic component, making it inappropriate as a measure by which to judge the
      health and nutritional status of a population.

PMID- 16431662
TI  - Metabolic effects of a short exposure to a hot environment in man.
AB  - Some metabolic effects of a 2h exposure to an environmental temperature of 48
      degrees C DB, 35 degrees C WB, have been studied in six male subjects. The
      results indicate that adrenal cortical activity does not necessarily increase as
      a result of exposure to moderate heat stress. However, a consistent increase in
      lipolysis may indicate increased sympatho-adrenal activity. There was a
      significant correlation between blood glucose and cortisol levels, suggesting
      that the increased sympathetic activity may be without effect on carbohydrate
      metabolism.

PMID- 16431663
TI  - Sexual maturation in Turkish girls.
AB  - Ages of attainment of successive puberty stages of the breast, public hair and
      axillary hair and of menarche were established in a cross-sectional study of 1468
      Turkish school girls in Istanbul. The subjects were grouped into four
      socioeconomic classes. Onset of secondary sexual characteristics and of menarche
      in the highest socioeconomic class were early as compared to other population
      groups. Mean ages of attainment for the initial stage of breast, pubic hair and
      axillary hair development were 9.8, 10.4 and 10.8 years respectively in this
      group. Mean menarcheal age was 12.36 +/- 0.01 years. All stages of breast, pubic
      hair and axillary hair and also menarche consistently occurred later in the lower
      socioeconomic classes as compared with the higher. The time intervals from onset
      to completion of secondary sexual characteristics were comparable to those
      reported for European girls for pubic and axillary hair development, but
      relatively longer for the development of the breast. They differed little between
      the socioeconomic classes.

PMID- 16431665
TI  - Premature pubarche and the growth of the trunk in paralysed children.
AB  - In a hospital supervising prolonged orthopaedic treatment of children suffering
      from neurological affections, isolated premature pubarche appeared very
      frequently in children suffering from severe paralytic sequelae of acute anterior
      poliomyelitis. These subjects had a greater progression of scoliosis and
      segmental disproportion than comparable subjects of the same age. Supine length
      and crown-rump length were studied during growth in 16 paralysed boys and 22
      paralysed girls with premature pubarche. The results were compared with those of
      two control populations, one normal group (274 girls, 246 boys), the other a
      paralysed group (49 boys and 38 girls). Paralysed children (group with premature
      pubarche and control group) all show considerable shortening of the legs. Up to
      age 11 for girls and 13 for boys, children with premature pubarche had longer
      trunks than normal, while supine length was normal. Premature slowing of growth
      then occurred, bringing the trunk to normal values and supine length to very low
      values for age. This is ascribed to premature pubertal growth of the trunk. The
      roles of hormonal changes and neurological damage are discussed.

PMID- 16431664
TI  - Colour-blindness and sensitivity to PTC in Hadza.
AB  - 211 Hadza (Tanzania) males, including members of both western and eastern groups,
      were tested for red-green colour blindness with the Ishihara non-numeral plates.
      Three closely related individuals were considered to be protanopes. It is
      possible that they received the gene from an Isanzu ancestor. 118 individuals
      (both sexes) were tested for taste-deficiency to PTC using a single solution and
      a sorting test. 22% of the males and 27% of the females were considered to be non
      tasters. Since this appeared to be a high figure for an African population a
      sample of 53 eastern Hadza males was later tested using solutions 1, 3, 5, 7, 9,
      11, 13. A conservative interpretation of the threshold distribution gave an
      estimate of 43% non-tasters. Corrections were applied for the inclusion of close
      relatives in the samples. The results are discussed in relation to other African
      data.

PMID- 16431666
TI  - The declines in dizygotic twinning rates and in birth rates.
AB  - It is suggested that, contrary to Elwood (1973), the current secular decline in
      age-specific dizygotic twinning rates is not due to the current decline in birth
      rates except to a minor extent.

PMID- 16431675
TI  - Models for cultural inheritance: a general linear model.
AB  - A theory of cultural evolution is proposed based on a general linear mode of
      cultural transmission. The trait of an individual is assumed to depend on the
      values of the same trait in other individuals of the same, the previous or
      earlier generation. The transmission matrix W has as its elements the
      proportional contributions of each individual (i) of one generation to each
      individual (j) of another. In addition, there is random variation (copy error or
      innovation) for each individual. Means and variances of a group of N individuals
      change with time and will stabilize asymptotically if the matrix W is irreducible
      and aperiodic. The rate of convergence is geometric and is governed by the
      largest non-unit eigenvalue of W. Groups fragment and evolve independently if W
      is reducible. The means of independent groups vary at random at a predicted rate,
      a phenomenon termed "random cultural drift". Variances within a group tend to be
      small, assuming cultural homogeneity. Transmission matrices of the teacher/leader
      type, and of parental type have been specifically considered, as well as social
      hierarchies. Various limitations, extensions, and some chances of application are
      discussed.

PMID- 16431676
TI  - The effect of parity on placental weight and birth weight: interaction with
      placental alkaline phosphatase polymorphism.
AB  - The effect of parity on placental weight and birth weight is examined through a
      series of birth records from an Indian population in Calcutta. Placental weight
      and birth weight increase with parity, the maximum increment occurring between
      parities 1 and 2. This is compatible with a hypothesis of sensitization of the
      mother to foetal, paternally derived, antigens. The three common placental
      alkaline phosphatase enzymic genotypes have no effect on determining foetal
      development.

PMID- 16431677
TI  - Hand preference and I.Q. in a group of Oxfordshire villages.
AB  - Verbal and performance scores in a standard intelligence test (WAIS) were
      considered in relation to patterns of hand preference (measured by questionnaire)
      in a large sample of the general population. Left-handers and mixed-handers did
      not obtain lower scores than right-handers. Indeed, there was a tendency for
      subjects who reported that they could use either hand for at least one of the
      questionnaire tasks to obtain higher I.Q.s. Otherwise, there were no significant
      differences in I.Q. with the exception of a consistent sex difference, in that
      men achieved higher scores on both verbal and performance scales.

PMID- 16431679
TI  - Sexual maturation in Turkish boys.
AB  - Ages of onset and attainment of various stages of secondary sexual characters
      were assessed from cross-sectional data on 1530 city schoolboys in Istanbul,
      Turkey. The subjects were grouped into four socio-economic classes. Ages of onset
      of pubic hair (11.80 years), axillary hair (13.15 years), facial hair (14.45
      years) and laryngeal development (13.37 years) were relatively early in the
      highest socioeconomic class and agreed with recent values reported for European
      boys. In lower socioeconomic classes there was a relative delay of onset and
      attainment of the subsequent stages of secondary sexual characters. Acne was
      encountered in a significant proportion of the boys and increased in frequency
      with age. Socioeconomic level had no effect on its frequency. Gynaecomastia,
      unilateral in nearly half of the instances, was encountered in 7.0 per cent of
      the subjects. The frequency of gynaecomastia was lower in class 1 boys.

PMID- 16431678
TI  - The relationship of variations in children's growth rates to seasonal climatic
      variations.
AB  - The growth rates in stature of 300 children in the Orkney Islands, measured at
      monthly intervals over 2 years, were negatively correlated with various measures
      of light and temperature. All correlations were small but statistically
      significant, the highest being with the mean of the maximal daily temperatures (
      0.32) for the boys and with hours of bright sunshine (-0.29) for the girls. The
      children's mean growth rates reached maxima at midwinter and minima at midsummer
      but the maximum in the winter 1971-72 was much lower than those at the beginning
      of 1971 and at the end of 1972. The climatic variables were not appreciably
      different in the two years. Only about 35 per cent of children showed cycles of
      growth rates which could be regarded as seasonal in that they rose to peak values
      at approximately the same time in the two successive years. The difference
      between the maximal and minimal rates exhibited by Orkney children (5.26+/-0.12
      cm/yr for boys; 5.46+/-0.14 cm/yr for girls) was almost identical to that in
      London children. The synchronization of the maximal growth rates was no more
      precise in Orkney than in London. It is concluded that seasonal variations in
      light and temperature exert at most only a small effect on growth rate and
      perhaps none at all. The influence of other factors, as yet unidentified, is
      greater.

PMID- 16431680
TI  - Acclimatization and maximum number of functioning sweat glands in Hindu and Dutch
      females and males.
AB  - The number and distribution of thermally (hot water bath method) activated
      eccrine sweat glands have been measured in Dutch, Hindu and Bushnegro males and
      in Dutch and Hindu females in Surinam. Results are compared with those for Dutch
      and Hindu males and females in the Netherlands. The results suggest that the
      maximum number of functioning sweat glands (F.S.G.) changes during natural
      acclimatization and that probably the relative magnitude of this change depends
      on the percentage of "recruitment type" adapters within each racial group. This
      change was not apparent for all sixteen body areas studied. In these experiments
      high relative humidity had no influence on the number of functioning sweat
      glands. No sex differences were observed in body density or in pattern of
      regional distribution. Only the Hindu and Dutch males differed significantly in
      body density. A positive relationship was observed between body density and
      extremities-weight ratio in the three male groups.

PMID- 16431681
TI  - Genetic and environmental influences on morphological characteristics.
AB  - Study has been made of 37 anthropometric measurements in a socially selected
      sample of 125 Belgian families, comprising parents and adult children. The parent
      child and mid-parent-child correlation coefficients indicate that the extent of
      genetic determination varies considerably from one measurement to another, being
      greatest in the longitudinal body measurements, least in the circumferences
      involving soft tissues and in measures of the nose and mouth. Further analysis of
      the intrafamilial correlation, and variance analysis by the method of Fisher and
      Gray (1937), shows that neither dominant nor X-linked loci exert any appreciable
      effects.

PMID- 16431682
TI  - Blood donor survey in the Isle of Bute.
AB  - The ABO records of 392 blood donors in the Isle of Bute, Scotland, showed a
      significant excess of group A and decrease of group O compared with data from the
      adjacent mainland. A survey by questionnaire to explain these observations
      assessed the representative nature of the donor panel as a sample of the Bute
      population, with respect to sex, age, occupation and origin by birthplace and
      parental birthplace. The reported motivations first prompting the Bute panel to
      donate blood were analysed, especially those liable to introduce bias into the
      results. It was concluded that: the informative 318 donors were not an atypical
      sample; inclusion of Younger Kindred enhanced the group A frequency; inclusion of
      donors with knowledge of their blood groups before enrolment as donors introduced
      a counter-bias in favour of group O; the raised group A frequency of the Incomers
      to the island was probably attributable to admixture of an English population
      with a non-Bute Scottish population; the Brandanes could represent a small
      indigenous island population in which the incidence of group A has become high,
      but, as numbers were small, a chance observation could not be excluded.

PMID- 16431683
TI  - Nutritional anthropometric measurements of male Tamil clerks in Madras (sea coast
      plains) and Ooty (hills).
AB  - The mean values and standard deviations of height, weight, bicristal diameter,
      arm girth and skinfold measurements at triceps and biceps of 315 Tamilian adult
      men from Madras (South India) and 318 adult men of the same ethnic, linguistic,
      socioeconomic and age groups from the Hill Station of Ooty (South India) are
      compared. Intercorrelations between age and six anthropometric parameters have
      also been presented separately for Madras and Ooty subjects. Body weight, arm
      girth and skinfold measurements were significantly higher in Madras subjects, and
      bicristal diameter measurements were significantly higher in Ooty subjects.
      Stature measurements were lower in Ooty subjects than Madras subjects but the
      difference was not statistically significant. In both Madras and Ooty subjects,
      highest positive correlations were observed between arm girth and body weight.
      The next highest correlation observed was between triceps-biceps skinfolds.

PMID- 16431826
TI  - Methadone: a double edged sword.

PMID- 16431827
TI  - The complementary and alternative medicine controversy continues: the IOM report.

PMID- 16431829
TI  - Pharmacokinetics of methadone.
AB  - Methadone is a synthetic opioid that is effective for the relief of moderate-to
      severe pain and for the treatment of opioid dependence. The pharmacokinetics of
      methadone differ from those of morphine in that methadone has a higher
      bioavailability, a much longer half-life, and is hepatically metabolized by
      cytochrome P450 enzymes. The pharmacokinetics of methadone are variable and an
      understanding of the factors that impact the onset, magnitude, and duration of
      analgesia is required to optimize therapy. Drug interactions are common and
      patients receiving methadone should be monitored closely for toxicity or
      therapeutic failure. Special populations in whom a change from the usual dosage
      regimen may be necessary include pediatric patients, patients with renal failure,
      the elderly, and pregnant women. To achieve an optimal dosage regimen, the
      clinician must have an understanding of the pharmacokinetics and pharmacodynamics
      of methadone in addition to the relationship between these variables and their
      patients' demographic and pathophysiologic characteristics. AMEDLINE search was
      performed to identify literature published between 1966 and May 2005 relevant to
      the pharmacokinetics of methadone. These publications were reviewed and the
      literature summarized regarding unique and clinically important elements of
      methadone disposition including its absorption profile, distribution, and
      metabolism/excretion. General dosing guidelines, dosage conversions from other
      opioids and pharmacokinetic issues in special populations are discussed.

PMID- 16431830
TI  - Development of guidelines for palliative care pharmacotherapy.
AB  - Despite limited evidence to support their use, hospice and palliative care
      programs commonly employ protocols and/or algorithms for symptom management. The
      use of these tools may assist in the standardization of care and help manage
      pharmacotherapy-related costs. The process used by one national palliative care
      pharmacy company to create palliative care guidelines and algorithms is described
      along with some of the challenges in validating such tools.

PMID- 16431831
TI  - Chronic arthritis pain management with topical morphine: case series.
AB  - Chronic pain is a major health problem in the United States affecting 50 to 75
      million Americans. The extent of pain encountered with chronic disease states may
      impact an individual's quality of life. Morphine is the drug of choice for severe
      pain. The primary purpose of the study was to determine analgesic response with
      the use of topical morphine to control chronic pain in a series of patients with
      arthritis pain. The second purpose was to detect the presence of morphine in the
      urine following topical administration and subsequently conclude that there had
      been systemic absorption of the drug. Three patients were prescribed topical
      morphine for chronic pain and were followed over the course of several weeks.
      Each patient was instructed to record the date and time of the topical morphine
      applications. When each patient had achieved a satisfactory level of pain control
      a 24-hour urine collection was obtained and taken to a laboratory for analysis.
      All patients reported a satisfactory degree of pain relief following topical
      application of morphine. The urine analysis confirmed the presence of morphine in
      the 24-hour samples. This analysis confirms systemic absorption of the morphine
      across intact skin; however the results cannot be used to quantify the degree of
      systemic absorption. Results of the study indicate that the use of topical
      morphine is effective in controlling chronic pain and topical morphine is
      absorbed systemically in the body.

PMID- 16431832
TI  - Life of pain, life of pleasure: pain from the patients' perspective--the
      evolution of the PAIN exhibit.
AB  - This commentary describes a person's experience with chronic pain, how his
      beliefs and understanding of pain resolved, and how he developed coping
      mechanisms and a focus for his life after developing chronic pain. His
      realization of how art was the most effective way to describe his pain experience
      to others and the resulting development of the pain visual arts exhibit PAIN
      Exhibit.com are described. Guidance for clinicians form the patient perspective
      is provided.

PMID- 16431833
TI  - Finding a balanced diet on the World Wide Web: nutrition at the end-of-life.
AB  - End-of-life decisions regarding nutrition should be formed in light of available
      scientific information and socio-culturally sensitive aspects of patient/family
      centered care. An extensive internet search was performed to identify available
      resources concerning nutrition at the end of life and guide health professionals
      and consumers in the interpretation and clinical application of information. The
      results of this search yielded several internet sites that post content that can
      be useful to clinicians, consumers and both. The amount of accessible information
      on the World Wide Web is so extensive that considerable effort is required to
      appraise the accuracy and scientific value of subject matter while balancing
      patients and families perceived importance of nourishment during the end stages
      of life. Therefore, Internet-based information on nutrition at the end of life is
      presented and evaluated for the relative contributions that this type of
      information offers to clinicians, patients and families.

PMID- 16431834
TI  - Assessing the value of hospice care: is documentation of cost savings necessary.
AB  - Hospice care is one end-of-life option that since its inception has been the
      subject of numerous cost comparisons. Early hospice care emerged as a social
      movement in the United Kingdom. This movement began outside the medical services
      establishment and sought to improve care for the terminally ill through
      palliative and supportive services, provided in the patient's own home (1).
      Hospice care was viewed as a dramatic shift away from the dominant medical
      paradigm that favored aggressive and technologically intensive treatment of
      advanced disease in an institutional setting. While many public and health policy
      analysts have attributed the high cost of dying to the use of aggressive and
      intensive treatments, the cost-savings of hospice is still an issue for debate.
      The results of the National Hospice study, which documented medical cost savings
      during the last six months of life for hospice patients as compared to
      conventional care patients, was seen as the impetus for Medicare reimbursement
      for hospice services (2,3). Against this backdrop, the Medicare Hospice Benefit
      was enacted in 1982 with the goal of providing humane, compassionate and cost
      effective care for Medicare beneficiaries with incurable advanced disease. Ever
      increasing concerns about rising health care costs and the economics of dying
      have fueled numerous studies trying to quantify the cost savings at the end of
      life that may result from hospice versus conventional care.

PMID- 16431835
TI  - Evidence-based pain management and palliative care in issue two for 2005 of the
      Cochrane Library.
AB  - The Cochrane Library of Systematic Reviews is published quarterly. It now
      contains 2356 complete reviews, 1569 protocols of reviews and 5205 one page
      summaries of systematic reviews published in the general medical literature. In
      addition there are citations of 446,156 randomised controlled trials, 19
      methodology reviews and 6855 cited papers in the Cochrane methodology register.
      The health technology assessment database contains 4548 citations. In this
      edition of the Library, there were 107 new reviews of which six have direct or
      potential relevance for practitioners in pain and palliative medicine. In 2004,
      the format of the citation has changed with the move to publication of the
      Cochrane Library by John Wiley & Sons. Citations will probably change again in
      the future as currently there is no indication of the date when a review was
      first published.

PMID- 16431836
TI  - Symptom control in end-of-life care: pain, eating, acute illnesses, panic
      attacks, and aggressive care.
AB  - This feature is based on actual questions and answers adapted from a service
      provided by the Hospice Foundation of America. Queries addressing the propriety
      of managing acute medical conditions in patients enrolled in a terminal care
      program and the mistaken belief that death from cancer is always painful are
      provided. Questions included in this set address management of acute medical
      conditions during end-of-life care, the lack of inevitability of pain with
      cancer, nutrition in advanced disease, managing panic attacks, and appropriate
      care for a dying 90 year old gentleman.

PMID- 16431837
TI  - Pain as the fifth vital sign: how can I tell when back pain is serious.
AB  - An increasingly common query from patients relate to the recommendation that pain
      be considered the fifth vital sign. The American Pan Society championed that
      effort several years ago to increase patients' awareness that pain should be
      asked about, monitored, and managed. Now the federal Department of Veterans
      Affairs has also adopted this terminology in its pain management programs.
      Another common question from patients is when back pain should be considered
      serious. These two topics are addressed in language suitable for patient
      counseling.

PMID- 16431838
TI  - Laryngospasm and bronchospasm following parecoxib injections.

PMID- 16431839
TI  - Analysis and recommendations for agency action regarding nonsteroidal
      antiinflammatory drugs and cardiovascular risk.
AB  - On April 6, 2005, the Directors of the Office of New Drugs and the Office of
      Pharmacoepidemiology and Statistical Science at the U. S. Food and Drug
      Administration posted the following information on the FDA website pertaining to
      analysis and recommendations for FDA action regarding nonsteroidal anti
      inflammatory drugs and cardiovascular risk.

PMID- 16431841
TI  - Artistic expressions of pain from Painexhibit.com.

PMID- 16431844
TI  - Oct-2 DNA binding transcription factor: functional consequences of
      phosphorylation and glycosylation.
AB  - Phosphorylation and O-GlcNAc modification often induce conformational changes and
      allow the protein to specifically interact with other proteins. Interplay of
      phosphorylation and O-GlcNAc modification at the same conserved site may result
      in the protein undergoing functional switches. We describe that at conserved
      Ser/Thr residues of human Oct-2, alternative phosphorylation and O-GlcNAc
      modification (Yin Yang sites) can be predicted by the YinOYang1.2 method. We
      propose here that alternative phosphorylation and O-GlcNAc modification at Ser191
      in the N-terminal region, Ser271 and 274 in the linker region of two POU sub
      domains and Thr301 and Ser323 in the POUh subdomain are involved in the
      differential binding behavior of Oct-2 to the octamer DNA motif. This implies
      that phosphorylation or O-GlcNAc modification of the same amino acid may result
      in a different binding capacity of the modified protein. In the C-terminal
      domain, Ser371, 389 and 394 are additional Yin Yang sites that could be involved
      in the modulation of Oct-2 binding properties.

PMID- 16431845
TI  - Characterization of 67 kD laminin receptor, a protein whose gene is overexpressed
      on treatment of cells with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide.
AB  - The molecular mechanisms potentially related to tumorigenesis induced by anti
      benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) were investigated by suppression
      subtractive hybridization of the human bronchial epithelial cells (16HBE)
      carcinoma induced by BPDE-transformed 16HBE cells (16HBE-C). The 67 kD laminin
      receptor gene (67LR1) is one of the screened overexpressed genes in 16HBE-C cells
      when compared with 16HBE. In order to understand the main functions of 67LR1
      gene, we amplified the full length of 67LR1 gene using reverse transcription
      polymerase chain reaction (RT-PCR) method. The amplified gene products were
      inserted into pcDNA 3.1 Directional TOPO expression vector. We then transfected
      16HBE cells with this vector and derived stable transfected 16HBE cell lines
      containing the 67LR1 gene by using lipofectin and G418 selection protocols. The
      expression products of transfected genes were analyzed by semiquantitative RT
      PCR. Soft agar growth assay was carried out to identify the malignant features of
      67LR1 gene. The stable transfected cell lines can form colonies in soft agar.
      Further, the transfected cells showed morphological changes compared to the
      control cells, such as the obvious pseudopods. These data suggest that the 67LR1
      gene may be related to malignant transformation induced by the anti-BPDE. The
      67LR1 protein may be related to the directionality of cell movement.

PMID- 16431846
TI  - Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase
      immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).
AB  - Oviduct epithelial cells are important for the nourishment and survival of
      ovulated oocytes and early embryos, and they respond to the steroid hormones
      estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic
      hydrocarbons (PHAH) are environmental toxins that act in part through the ligand
      activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor),
      and exposure to PHAH has been shown to decrease fertility. To investigate effects
      of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type
      endocrine disruptors, we have established a novel telomerase-immortalized oviduct
      porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase
      and the immunoreactive epithelial marker cytokeratin but lacked the stromal
      marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and
      AhR, as determined by the detection of ER-alpha- and AhR-specific target
      molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) resulted in a significant increase in the production of the
      cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation
      of ER nuclear protein fraction and significantly decreased ER-signaling in TERT
      OPEC as determined by ERE-luciferase transient transfection assays. In summary,
      the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest
      that PHAH affect the predominantly estrogen-dependent differentiation of the
      oviduct epithelium within the fallopian tube. This action then alters the local
      endocrine milieu, potentially resulting in a largely unexplored cause of impaired
      embryonic development and female infertility.

PMID- 16431847
TI  - Src tyrosine kinases mediate crystalline silica-induced NF-kappaB activation
      through tyrosine phosphorylation of IkappaB-alpha and p65 NF-kappaB in RAW 264.7
      macrophages.
AB  - Protein tyrosine kinases (PTKs) and mitogen-activated protein kinases (MAPKs)
      have been demonstrated to play a crucial role in the signaling pathways induced
      by silica. In the present study, we investigated whether Src family TKs play a
      role in crystalline silica-induced NF-kappaB activation and whether NF-kappaB
      activation requires Src TK-dependent MAPK activity in RAW 264.7 cells, a mouse
      peritoneal macrophage cell line. Selective Src TK inhibitors, damnacanthal or
      PP1, inhibited silica-induced NF-kappaB activation in a dose-dependent manner.
      Furthermore, these kinase inhibitors suppressed silica-induced tyrosine
      phosphorylation of IkappaB-alpha and p65 NF-kappaB. Within a similar time frame,
      c-Src and Lck were physically associated with IkappaB-alpha and with p65 NF
      kappaB. Silica stimulated the phosphorylation of extracellular signal-regulated
      kinase 1 and 2 (ERK1/2), but not p38 MAPK and c-Jun NH(2)-terminal kinase 1 and 2
      (JNK1/2). Damnacanthal or PP1 substantially blocked the silica-induced activation
      of ERK1/2. Moreover, PD98059, an inhibitor of ERK1/2, or SB203580, an inhibitor
      of p38 MAPK, failed to inhibit silica-induced NF-kappaB activation. These results
      suggest that c-Src and Lck act for silica-induced NF-kappaB activation by
      mediating the tyrosine phosphorylations of IkappaB-alpha and p65 NF-kappaB.
      However, the Src TK-dependent activation of ERK1/2 may not be involved in the
      silica signaling pathway leading to NF-kappaB activation.

PMID- 16431848
TI  - Organic extracts of urban aerosol (< or =PM2.5) enhance rBet v 1-induced
      upregulation of CD63 in basophils from birch pollen-allergic individuals.
AB  - Epidemiological studies have linked the high prevalence rates of IgE-mediated
      allergic diseases to an increase in exposure to traffic-related air pollutants
      such as diesel exhaust particles (DEPs). There is growing experimental evidence
      that organic compounds of DEPs, predominantly polycyclic aromatic hydrocarbons
      (PAHs), participate in the development and maintenance of allergic airway
      diseases. In this study we investigated the impact of organic extracts of urban
      aerosol (AERex) containing various PAH concentrations on the activation of human
      basophils. Whole blood samples from six birch pollen-allergic and five control
      subjects were repeatedly incubated in the presence of AERex with or without
      recombinant Bet v 1 (rBet v 1). Basophils were analyzed for CD63 expression as a
      measure of basophil activation by using multiparameter flow cytometry. Basophils,
      when exposed in vitro to AERex and rBet v 1, expressed CD63 significantly more
      than with antigen activation alone. AERex synergized with rBet v 1 in a dose
      dependent manner, but did not activate basophils from nonallergic donors. AERex
      effect on CD63 upregulation was found in blood samples of all patients and did
      not occur in the absence of rBet v 1. Strongest basophil activation was monitored
      upon stimulation with AERex comprising the highest PAH content. The capability of
      AERex to increase activation of basophils from birch pollen-allergic subjects at
      ambient concentrations suggests an important role of organic compounds of
      airborne particles in the aggravation of IgE-mediated allergic diseases. This
      could be a new aspect of regulation of unspecific promoting stimuli in clinical
      manifestation of allergic inflammation.

PMID- 16431849
TI  - Evolution of circular permutations in multidomain proteins.
AB  - Modular rearrangements play an important role in protein evolution. Functional
      modules, often tantamount to structural domains or smaller fragments, are in many
      cases well conserved but reoccur in a different order and across many protein
      families. The underlying genetic mechanisms are gene duplication, fusion, and
      loss of sequence fragments. As a consequence, the sequential order of domains can
      be inverted, leading to what is known as circularly permutated proteins. Using a
      recently developed algorithm, we have identified a large number of such
      rearrangements and analyzed their evolutionary history. We searched for examples
      which have arisen by one of the three postulated mechanisms: independent
      fusion/fission, "duplication/deletion," and plasmid-mediated "cut and paste." We
      conclude that all three mechanisms can be observed, with the independent
      fusion/fission being the most frequent. This can be partly attributed to highly
      mobile domains. Duplication/deletion has been found in modular proteins such as
      peptide synthases.

PMID- 16431850
TI  - Evolution of programmed DNA rearrangements in a scrambled gene.
AB  - Gene unscrambling in spirotrichous ciliates involves massive genome-wide DNA
      deletion and rearrangement events during development. During each sexual cycle,
      the somatic nucleus (macronucleus) regenerates from the germ line nucleus
      (micronucleus). Development of the polyploid somatic genome requires programmed
      DNA deletion of micronuclear-limited intragenic noncoding sequences and
      permutation and amplification of the protein-coding regions. Recent studies
      suggest that, despite novel insertions of endogenous transposon or foreign DNA
      into the germ line genome, ciliates possess a whole-genome surveillance system
      that guides the recapitulation of a functional somatic genome. This renders the
      germ line genome an extremely dynamic structure over evolutionary time. Here we
      describe the germ line and somatic architectures of the gene encoding alpha
      telomere-binding protein in three early-diverging species (Holosticha sp.,
      Uroleptus sp., and Paraurostyla weissei) and trace the natural history of DNA
      rearrangements in this gene in six species, including three previously studied
      oxytrichids. Comparisons of homologous coding regions between earlier and later
      diverging species provide evidence for fusion of scrambled germ line fragments as
      small as 24 bp during evolution, as well as simultaneous fragmentation and
      scrambling of the germ line locus and shifting of the boundaries between coding
      and noncoding DNA, leading to distinct gene architectures in each species. We
      infer an evolutionary recombination pathway that passes through identified
      intermediate species and gives rise to the observed patterns in all known
      species, capitalizing on their unique DNA rearrangement machinery and germ line
      flexibility.

PMID- 16431851
TI  - Management of hypertension in the oldest old: a study in primary care in New
      Zealand.
AB  - BACKGROUND: The benefits of blood pressure (BP) lowering are well established
      except in the oldest old, and suboptimal control of hypertension has been found
      in many different populations. OBJECTIVE: To assess the frequency of hypertension
      and its adequacy of management in the oldest old in primary care. DESIGN: a cross
      sectional study. SETTING: Sixty-seven general practitioners (GPs) in three urban
      centres in New Zealand. METHODS: We conducted structured reviews of medical
      records for all ambulatory people aged > or = 80 years who were registered with a
      participating GP. Hypertensive status and BP control were classified according to
      standard criteria. Logistic regression analyses were used to identify independent
      factors for BP control. RESULTS: Medical records of 3,068 people (mean age 85
      years, 64% female) revealed 56% to be hypertensive, of whom 94% were on treatment
      and 58% had controlled BP levels. Major co-morbid conditions were common among
      hypertensive people, and half of them had associated target organ damage.
      Histories of stroke, heart disease and hypercholesterolaemia were independent
      factors for good BP control. CONCLUSION: A large proportion of the oldest old
      were currently receiving anti-hypertensive therapy, and most had adequately
      controlled BP. Previous vascular disease was the most important factor for both
      BP treatment and control. These findings indicate a high level of uptake of
      cardiovascular guidelines for older people.

PMID- 16431852
TI  - Hyperostosis frontalis interna associated with hypogonadism in an elderly man.
AB  - Hyperostosis frontalis interna (HFI), symmetric thickening of the inner table of
      the frontal bone, is relatively common in women but very rare in men. We report
      the case of an elderly male patient with HFI. This patient was accompanied by
      primary hypogonadism, which may be related to the underlying pathogenesis of HFI.

PMID- 16431853
TI  - Sexual health and the new ageing.

PMID- 16431854
TI  - Towards living long and being healthy--the challenge for liaison psychiatric
      services for older adults.

PMID- 16431855
TI  - A cross-sectional survey of health state impairment and treatment patterns in
      patients with postherpetic neuralgia.
AB  - BACKGROUND: Postherpetic neuralgia (PHN) develops in 8-24% of patients with
      herpes zoster. Few studies have evaluated the patient burden and treatment of PHN
      in general practice. OBJECTIVES: To determine the patient burden of PHN with
      respect to pain intensity and impact on patient functioning and to characterise
      treatment patterns and health resource utilisation in general practice. METHODS:
      Eighty-four patients with PHN were identified in general practice settings during
      an observational survey of neuropathic pain syndromes in six European countries.
      Patients answered a questionnaire that included: pain severity and interference
      items from the modified short form brief pain inventory (mBPI-SF); EuroQol (EQ
      5D) survey; and questions related to current treatment, health status and
      resource utilisation. Physicians provided information on medications prescribed
      for PHN and pain-related co-morbidities (anxiety, depression and sleep
      disturbance). RESULTS: Mean patient age was 71.0 +/- 12.8 years, 76% were > or =
      65 years and 45% of patients had PHN > or = 1 year. The mean pain severity index
      was 4.2, reflecting moderate pain despite 89% of patients taking prescription
      medications for PHN. Few medications with demonstrated efficacy against PHN (e.g.
      carbamazepine and gabapentin) were prescribed, often at suboptimal doses. Pain
      severity was associated with reduced EQ-5D health state valuation (P<0.001),
      greater pain interference on all domains (P<0.001) and increased health resource
      utilisation (P = 0.008). CONCLUSIONS: PHN causes substantial patient burden
      expressed as interference with daily functioning and reduced health status
      associated with pain severity. This burden may result in part from suboptimal
      management strategies and suggests a need for more effective pain management.

PMID- 16431856
TI  - Treatment with caspofungin in immunocompromised paediatric patients: a
      multicentre survey.
AB  - OBJECTIVES: Although a paediatric dosage has not been established, caspofungin is
      occasionally used in paediatric patients. We conducted a multicentre
      retrospective survey to obtain data on immunocompromised paediatric patients
      considered to require caspofungin therapy. METHODS: The survey identified 64
      patients (median age: 11.5 years; 25 females, 39 males) with haematological
      malignancies (48), marrow failure (9), solid tumours (3), haematological
      disorders (2) and congenital immunodeficiency (2) who received caspofungin for
      proven (17), probable (14) and possible (17) invasive fungal infections or
      empirically (16). Caspofungin was administered until intolerance or maximum
      efficacy at dosages individually determined by the responsible physician for
      refractory infection (38), intolerance of other agents (10) or as best
      therapeutic option (16). RESULTS: The 64 patients received caspofungin for a
      median of 37 days (range 3-218) as single agent (20) or in combination (44). The
      median daily maintenance dosage was 1.07 mg/kg (95% CI 1.09-1.35; range 0.40
      2.92) or 34.3 mg/m2 (95% CI 32.3-37.3; range 16.3-57.5). In none of the patients
      was therapy discontinued due to adverse events (AEs). Clinical AEs were mild to
      moderate and observed in 34 patients (53.1%). While mean glutamate pyruvate
      transaminase and glutamate oxalate transaminase values were slightly (P < 0.005)
      higher at the end of treatment (EOT), serum bilirubin, alkaline phosphatase and
      creatinine values were not different from baseline. Complete responses, partial
      responses or stabilization were observed in 5/7/3 of 17 patients with proven, in
      3/4/3 of 14 patients with probable and in 7/6/1 of 15 evaluable patients with
      possible invasive infections. Thirteen of 16 patients on empirical therapy
      completed without breakthrough infection. Overall survival was 75% at the EOT and
      70% at 3 months post-EOT, respectively. CONCLUSIONS: Caspofungin displayed
      favourable safety and tolerance and may have useful antifungal efficacy in
      severely immunocompromised paediatric patients.

PMID- 16431857
TI  - Outbreak of multiple clones of imipenem-resistant Acinetobacter baumannii
      isolates expressing OXA-58 carbapenemase in an intensive care unit.
AB  - OBJECTIVES: To investigate the resistance mechanisms and the genetic relationship
      of imipenem-resistant Acinetobacter baumannii isolates recovered in the intensive
      care unit (ICU) of a tertiary care hospital. METHODS: Imipenem-resistant A.
      baumannii clinical and environmental isolates were collected in the ICU of the
      Red Cross General Hospital, Athens, Greece between March and October 2002. The
      isolates were tested by Etest MBL, PCR, RT-PCR and sequencing for carbapenemase
      encoding genes, PFGE and synergy experiments using meropenem and the efflux pump
      inhibitor carbonyl cyanide chlorophenylhydrazone. RESULTS: During the study
      period, 15 clinical and two environmental imipenem-resistant (MIC 8 to >128 mg/L)
      A. baumannii isolates were recovered. PFGE showed six different clones that
      included both clinical and environmental isolates. All 17 isolates were negative
      by Etest MBL and PCR for genes bla(IMP), bla(VIM), bla(SPM), bla(OXA-23-like) and
      bla(OXA-24-like). Genes bla(OXA-51-like) and bla(OXA-58-like) were amplified from
      15 and 14 isolates, respectively. Sequencing of bla(OXA-51-like) amplicons
      identified bla(OXA-66) (nine cases) and bla(OXA-69) (six cases), whereas bla(OXA
      58-like) sequences were classical bla(OXA-58). Reverse transcriptase-PCR showed
      that bla(OXA-51-like) genes were expressed in 12 and bla(OXA-58) in 10 isolates;
      in these isolates, inhibition of OXA enzymes by 200 mM of NaCl reduced carbapenem
      MICs by up to 4-fold. Overexpression of proton-gradient dependent efflux pumps
      did not contribute to carbapenem resistance in any isolate. Similarly, although
      AmpC expression was demonstrated in eight isolates, inhibition of AmpC with
      cloxacillin did not reduce the MICs of carbapenems significantly. CONCLUSIONS:
      These findings indicate wide dissemination of OXA-58 carbapenemase, which
      contributes, at least partially, to the imipenem resistance of unrelated A.
      baumannii isolates in our ICU.

PMID- 16431858
TI  - Comment on: linezolid use in sepsis due to methicillin-susceptible Staphylococcus
      aureus.

PMID- 16431859
TI  - Molecular epidemiology of macrolide resistance in beta-haemolytic streptococci of
      Lancefield groups A, B, C and G and evidence for a new mef element in group G
      streptococci that carries allelic variants of mef and msr(D).
AB  - OBJECTIVES: To study the molecular mechanisms of erythromycin resistance in beta
      haemolytic streptococci of Lancefield groups A, B, C and G. METHODS: Erythromycin
      resistant clinical isolates from North East Scotland were collected over 2 years.
      Resistance phenotypes were determined by disc diffusion and MICs by Etest.
      Resistance genes mef, msr(D), erm(B) and erm(TR) were identified by PCR and mef
      and msr(D) were sequenced. RESULTS: Erythromycin resistance prevalence was 1.9%
      in group A streptococci (31 of 1625), 4.3% in group B (53 of 1233), 3.8% in group
      C (18 of 479) and 6.2% in group G (64 of 1034). The numbers of resistant isolates
      available were 26, 42, 9 and 52 in each group respectively. The majority of
      resistant isolates in groups A (57.7%, 15 of 26), B (88.1%, 37 of 42) and G
      (90.4%, 47 of 52) were MLS(B). The contribution of M phenotype was significant in
      groups C (77.8%, 7 of 9) and A (42.3%, 11 of 26). Group A isolates carried mef(A)
      and group B carried mef(E) exclusively. A mef sequence distinct from mef(A) and
      mef(E) was identified in group G and was associated with a new msr(D) sequence.
      These sequence variants appear to be part of a new genetic element that is
      inserted in the comEC gene. A bimodal distribution of erythromycin MICs was noted
      in erm(TR) isolates. CONCLUSIONS: The results demonstrate significant differences
      in the mechanisms of macrolide resistance amongst different Lancefield groups in
      the same geographical area. New sequences show that resistance mechanisms are
      still evolving.

PMID- 16431860
TI  - Characterization of a clinical isolate of Haemophilus influenzae with a high
      level of fluoroquinolone resistance.

PMID- 16431861
TI  - Infrequent occurrence of single mutations in topoisomerase IV and DNA gyrase
      genes among US levofloxacin-susceptible clinical isolates of Streptococcus
      pneumoniae from nine institutions (1999-2003).
AB  - OBJECTIVES: Prevalence of single quinolone-resistance determining region (QRDR)
      mutations in Streptococcus pneumoniae was studied from nine institutions over 5
      years to track the incidence of single QRDR mutations. METHODS: All 1106
      levofloxacin-susceptible pneumococci (MICs < or = 2.0 mg/L) identified from 1112
      total isolates (99.5% susceptibility) in TRUST 3 (1999), TRUST 5 (2001) and TRUST
      7 (2003) surveillance studies from the same nine hospitals in nine states were
      screened for QRDR mutations. Using pyrosequencing, the strains were screened for
      mutations corresponding to hot spots Asp-78, Ser-79 and Asp-83 in ParC; Asp-80,
      Ser-81 and Glu-85 in GyrA; Asp-435 in ParE and Asp-435 in GyrB. DNA sequencing of
      QRDRs was performed to confirm mutations. RESULTS: No QRDR mutations were found
      in any of the isolates with levofloxacin MICs < or = 0.5 mg/L and no gyrA or gyrB
      QRDR mutations were found in any of the screened isolates (MICs < or = 2 mg/L).
      Four single-step QRDR mutants with the following amino acid substitutions were
      found: ParE Asp-435 to Asn (isolated in 1999 in Colorado); ParC Asp-83 to Asn
      (isolated in 2001 in Kentucky); ParC Ser-79 to Phe (isolated in 2003 in Indiana)
      and ParC Ser-79 to Tyr (isolated in 2003 in California). These non-clonal strains
      had levofloxacin MICs of 1 mg/L and were non-susceptible to ciprofloxacin (MIC 2
      4 mg/L). CONCLUSIONS: Overall prevalence of single QRDR mutations in levofloxacin
      susceptible S. pneumoniae with MICs of < or = 2 mg/L was 0.4% (4/1106) and has
      remained <1% within nine institutions over 5 years (1999-2003).

PMID- 16431862
TI  - Dawn of non-nucleoside inhibitor-based anti-HIV microbicides.
AB  - The emergence of HIV/AIDS as a disease spread through sexual intercourse has
      prompted the search for safe and effective vaginal and rectal microbicides for
      curbing mucosal viral transmission via semen. Since endogenous reverse
      transcription is implicated in augmenting the sexual transmission of HIV-1
      infection, potential microbicides should have the inherent ability to optimally
      inhibit both wild-type and drug-escape mutants. The non-nucleoside reverse
      transcriptase inhibitors (NNRTIs), which bind to an allosteric site on RT, are an
      important arsenal of drugs against HIV-1. The clinical success of NNRTI-based
      HIV/AIDS therapies has led to extensive structural and molecular modelling
      studies of enzyme complexes and chemical synthesis of second- and third
      generation NNRTIs. Rationally designed NNRTIs deduced from changes in binding
      pocket size, shape and residue character that result from clinically observed
      NNRTI resistance-associated mutations exhibit high binding affinity for HIV-1 RT
      and robust anti-HIV activity against the wild-type and drug-escape mutants
      without cytotoxicity. Notably, membrane permeable tight binding NNRTIs have the
      ability to inactivate cell-free as well as cell-associated HIV-1 in semen without
      metabolic activation. Consequently, NNRTIs currently under development as
      experimental microbicides include thiourea-PETT (where PETT stands for
      phenethylthiazolylthiourea) derivatives (PHI-236, PHI-346 and PHI-443), urea-PETT
      derivatives (MIV-150), oxypyrimidines (S-DABOs), thiocarboxanilides (UC-781) and
      diarylpyrimidines (TMC-120). Mucoadhesive formulations of these NNRTIs have been
      studied for safety and efficacy in animal models and some have entered Phase I
      safety testing in humans. This review focuses on the structural, biological and
      preclinical studies relevant to the clinical development of these NNRTIs as
      molecular virucides intended to prevent the sexual transmission of HIV-1.

PMID- 16431863
TI  - In vitro antibacterial activities of tigecycline in combination with other
      antimicrobial agents determined by chequerboard and time-kill kinetic analysis.
AB  - OBJECTIVES: This study was undertaken to determine the interaction of tigecycline
      with 13 select antimicrobial agents against a wide variety of Gram-negative and
      Gram-positive bacterial isolates. METHODS: Antibiotic interactions were assayed
      using the chequerboard MIC format and selected synergistic combinations were
      confirmed using time-kill kinetic analysis. RESULTS: Microdilution chequerboard
      analysis of tigecycline in combination with amikacin, ampicillin/sulbactam,
      azithromycin, ciprofloxacin, colistin, imipenem, levofloxacin, piperacillin,
      piperacillin/tazobactam, polymyxin B, rifampicin, minocycline and vancomycin
      resulted in an interpretation of either no interaction or synergy. Time-kill
      kinetic analysis resulted in an interpretation of no interaction for all but one
      of the drug combinations that resulted in an interpretation of synergy by the
      chequerboard analysis. Antagonism was not observed for any combination when
      assayed by either method. CONCLUSIONS: The lack of antagonism seen with
      tigecycline combinations in both chequerboard and time-kill kinetic studies is an
      encouraging outcome, suggesting that tigecycline may prove to be effective in
      combination therapy as well as in monotherapy.

PMID- 16431864
TI  - Role of novel gyrA mutations in the suppression of the fluoroquinolone resistance
      genotype of vaccine strain Salmonella Typhimurium vacT (gyrA D87G).
AB  - OBJECTIVES: This study was aimed at characterizing the gyrA locus and determining
      its impact on fluoroquinolone susceptibility, DNA supercoiling degree and growth
      rate of Salmonella Typhimurium live vaccine strain vacT in comparison with its
      parent M415. Furthermore, the role of multiple drug resistance efflux in the
      susceptibility of vacT to fluoroquinolones and macrolides was investigated.
      METHODS: DNA sequences were determined for genes gyrA, gyrB, parC and parE of
      M415 and three consecutive mutants Nal2ori, Nal2passage and vacT. The impact of
      gyrA mutations on the fluoroquinolone susceptibilities and relative DNA
      supercoiling degrees was investigated by a complementation assay using wild-type
      gyrA (gyrA+) and a reporter gene system, respectively. Doubling times of the
      strains and MICs of different antibiotics in the absence and presence of an
      efflux pump inhibitor (EPI) were determined. RESULTS: Besides the gyrA mutation
      D87G, two novel mutations (G75A and A866S) were identified in the three mutants
      and a third novel mutation W59R in vacT. Fluoroquinolone susceptibilities and DNA
      supercoiling degrees of all three mutants were reduced compared with those of
      M415. Introduction of the gyrA+ allele restored fluoroquinolone susceptibilities
      of the two intermediate strains to the wild-type level; however, for vacT, MICs
      of fluoroquinolones were reduced below those of M415. VacT had a higher
      susceptibility to macrolides and the EPI compared with M415. CONCLUSIONS: The
      data point to a combination of at least one non-gyrA mutation and novel gyrA
      mutation(s) as the basis for the unusual fluoroquinolone susceptibility of vacT.

PMID- 16431865
TI  - Assessing the reliability of standardized performance indicators.
AB  - OBJECTIVE: . To investigate the reliability of self-reported standardized
      performance indicators introduced by the Joint Commission on Accreditation of
      Healthcare Organizations in July 2002 and implemented in approximately 3400
      accredited US hospitals. The study sought to identify the most common data
      quality problems and determine causes and possible strategies for resolution.
      DESIGN: Data were independently reabstracted from a random sample of 30
      hospitals. Reabstracted data were compared with data originally abstracted, and
      discrepancies were adjudicated with hospital staff. Structured interviews were
      used to probe possible reasons for abstraction discrepancies. RESULTS: The mean
      data element agreement rate for the 61 data elements evaluated was 91.9%, and the
      mean kappa statistic for binary data elements was 0.68. The rate of agreement for
      individual data elements ranged from 100 to 62.4%. The mean difference between
      calculated indicator rates was 4.88% (absolute value) and the range of
      differences was 0.0-13.3%. Symmetry of disagreement among original abstractors
      and reabstractors identified eight indicators whose differences in calculated
      rates were statistically unlikely to have occurred through random chance (P <
      0.05). CONCLUSION: Although improvement in the accuracy and completeness of the
      self-reported data is possible and desirable, the baseline level of data
      reliability appears to be acceptable for indicators used to assess and improve
      hospital performance on selected clinical topics.

PMID- 16431866
TI  - Increasing children's physical activity levels during recess periods in
      elementary schools: the effects of providing game equipment.
AB  - BACKGROUND: During recess, children can be active on a daily basis, making it an
      important school environmental factor for the promotion of health-related
      physical activity. The aim of the present study was to investigate the effects of
      providing game equipment on children's physical activity levels during morning
      recess and lunch break in elementary schools. METHODS: Seven elementary schools
      were randomly assigned to the intervention group (four schools), including 122
      children (75 boys, 47 girls, mean age: 10.8 +/- 0.6 years), and to the control
      group (three schools), including 113 children (46 boys, 67 girls, mean age: 10.9
      +/- 0.7 years). Children's activity levels were measured before and three months
      after providing game equipment, using MTI accelerometers. RESULTS: During lunch
      break, children's moderate and vigorous physical activity significantly increased
      in the intervention group (moderate: from 38 to 50%, vigorous: from 10 to 11%),
      while it decreased in the control group (moderate: from 44 to 39%, vigorous: from
      11 to 5%). At morning recess, providing game equipment was effective in
      increasing children's moderate physical activity (from 41 to 45%), while it
      decreased in the control group (from 41 to 34%). CONCLUSION: Providing game
      equipment during recess periods was found to be effective in increasing
      children's physical activity levels. This finding suggests that promoting
      physical activity through game equipment provision during recess periods can
      contribute to reach the daily activity levels recommended for good health.

PMID- 16431867
TI  - Assessing university students' health needs: lessons learnt from Crete, Greece.

PMID- 16431868
TI  - Changes in primary health care centres over the transition period in Slovenia.
AB  - BACKGROUND: Primary health care centres (PHCCs) were a characteristic of the
      former Yugoslav health care system introduced widely in Slovenia. Transition
      brought structural changes to health care and the position of the PHCC's was
      challenged. This paper investigates (i) PHCCs' perception of transition changes
      in health care, (ii) changes in resources and services, and (iii) changes in the
      relationships between PHCCs and new primary health care providers. METHODS: We
      mailed a self-administered questionnaire with 42 questions divided into 8
      chapters and related to the period between 1990 and 2000 to all 65 PHCCs in
      Slovenia. Questions were of three types, grouped according to the aspects we were
      trying to explore: perceived changes, actual changes and relations with new
      providers. RESULTS: We obtained 57 questionnaires representing PHCC catchment
      areas covering 93.7% of the Slovenian population. Municipalities' position versus
      PHCCs was reinforced but their role remains ambiguous. The number of employees
      was reduced by one third, capital investments are still ongoing, but the scope
      and volume of services has shrunk. Relations with the Health Insurance Institute
      of Slovenia (HIIS) were considered controversial while the influence of the
      public providers' association is perceived as marginal. CONCLUSIONS: PHCCs have
      survived the transition both structurally as well as functionally. However, an
      unstructured approach to system changes in primary care, a poorly managed process
      of introducing private provision, and a monopoly position of the HIIS affected
      their situation. The challenges for the future will be in preserving their public
      health functions, in increasing efficiency and in establishing clearly defined
      relations with private providers.

PMID- 16431869
TI  - Natural deaths in male prisoners: a 20-year mortality study.
AB  - BACKGROUND: Although morbidity is high in prisoners compared with the general
      population, uncertainty exists over rates for natural causes of death. We
      investigated natural deaths in prisons in England and Wales over a 20-year
      period. METHODS: All men who died in English and Welsh prisons from 1978-1997
      were identified. All deaths received a post-mortem. Death certificates were
      obtained to provide mortality information according to ICD-9. Standardised
      mortality ratios (SMRs) for major causes of natural death were calculated in
      those <60 years. RESULTS: 574 male prisoners died in custody from natural deaths,
      of which 307 (53%) deaths were from circulatory diseases and 91 (16%) from
      respiratory causes. Overall, SMRs for natural deaths were significantly lower
      than the general population (SMR = 0.70; 95% CI = 0.65-0.76). However, SMRs from
      respiratory pneumonia (SMR = 2.35; 1.75-3.16) and from other infectious causes
      were higher (SMR = 1.52; 1.03-2.23). CONCLUSION: There are important
      methodological challenges in calculating SMRs in prisoners. Bearing these in
      mind, we found increased mortality ratios for respiratory pneumonia and other
      infections. These findings highlight the need for the screening and effective
      treatment of infectious diseases in prisoners.

PMID- 16431870
TI  - Social equalization in youth: evidence from a cross-sectional British survey.
AB  - BACKGROUND: A number of studies have suggested that social inequalities in health
      disappear or are attenuated in early adolescence possibly due to changing risk
      exposures. The present study examines social equalization in youth in a
      representative sample of British households with children aged 0-18 years.
      METHODS: Secondary analysis of a cross-sectional survey of a representative
      sample of British households with children and youth with parent-reported less
      than good health, long-standing illness, and chest problems as outcomes. RESULTS:
      Data were available on 15 756 children aged 0-18 years in 8541 households in the
      third sweep (2001) of the British government's Families and Children Study.
      Parent-rated health status, long-standing illness, and chest problems all showed
      social patterning among children who were 0-11 years of age. Among 12- to 14-year
      olds, the social gradients in these outcomes noted in childhood associated with
      income, social class, and education were lost but inequalities in parent-rated
      health status and long-standing illness but not chest problems persisted
      associated with measures of household work status and wealth. Among 15- to 18
      year-olds, income inequalities appeared to reassert themselves, particularly
      among girls, but gradients by maternal education noted among 0- to 11-year-olds
      were absent in both sexes. Inequalities persisted with measures of household
      worklessness and wealth. CONCLUSIONS: In this cross-sectional study, the social
      equalization in youth was noted for some health outcomes and by some measures of
      socioeconomic status but not for others. Inequalities in parent-rated health
      status and long-standing illness persist among young people in workless
      households and those experiencing severe material hardship.

PMID- 16431871
TI  - Peer education in HIV prevention: an evaluation in schools.
AB  - BACKGROUND: In recent years a number of publications have come out about the peer
      education method used as a tool in HIV prevention for young people. Our survey
      aimed at testing the effectiveness of the peer education method in HIV prevention
      in high school settings through a pilot intervention. METHODS: A peer education
      intervention took place in 10 high schools in Athens over a 1 year period. A
      cohort of 702 students was surveyed (n = 493 intervention group, n = 209 control
      group) from 13 high schools through anonymous questionnaires based on the KABPs
      model, pre- and post-intervention. The statistical package used was SPSS using
      the chi(2)-test. RESULTS: Compared with control students, the intervention
      students were slightly empowered: (i) to increase their personal responsibility;
      and (ii) to adopt a safer behaviour in sexual practice. Knowledge did not show
      any significant modification between the two groups. However, discrimination
      about certain groups of people, the attitude about condoms and initiation of
      sexual relations did not appear to be influenced. CONCLUSIONS: The peer education
      approach can influence the behaviour of young people regarding their personal
      protection from HIV infection. In order to test its effectiveness, peer education
      should be further evaluated as a health education method in HIV prevention in
      high schools, other youth settings and community interventions, where the aim is
      behavioural change.

PMID- 16431872
TI  - Left ventricular dyssynchrony and dynamic functional mitral regurgitation:
      relationship or association?

PMID- 16431873
TI  - Normal range of N-terminal pro-brain natriuretic peptide: a note of caution.

PMID- 16431874
TI  - Feasibility of real-time magnetic resonance-guided stent-graft placement in a
      swine model of descending aortic dissection.
AB  - AIMS: To evaluate the pre-clinical feasibility of real-time magnetic resonance
      imaging (rtMRI) to guide stent-graft placement for experimental aortic dissection
      (AD) and to alleviate disadvantages of ionising radiation and nephrotoxic
      contrast media. Endovascular stent-graft placement for thoracic aortic disease is
      usually performed under X-ray guidance. The feasibility of rtMRI-guided stent
      graft placement is currently not known. METHODS AND RESULTS: By using a catheter
      based technique, dissections of the descending thoracic aorta were successfully
      created in eight domestic pigs. Subsequent implantation of commercially
      available, nitinol-based stent-grafts was performed entirely under rtMRI
      guidance. By pre-interventional MRI, the mean minimal true-lumen diameter was 0.9
      (0.825-0.975) cm. rtMRI permitted not only the successful and safe device
      navigation within the true lumen from the iliac arteries to the thoracic aorta,
      but also the precise positioning and deployment of the stent-graft and safe
      withdrawal of the delivery catheter in seven of eight pigs. This was achieved
      without any other complications. After the stent-graft placement, MRI
      demonstrated complete obliteration of the false lumen, which was confirmed at
      autopsy. All stent-grafts were well expanded resulting in an increase in the size
      of the true-lumen diameter to 2.05 (1.925-2.1) cm (P=0.066 vs. baseline).
      CONCLUSION: In experimental AD, rtMRI-guided endovascular stent-graft placement
      is feasible and safe and has the potential for mitigating radiation and contrast
      related side effects. Additionally, it allows not only pre-interventional
      diagnosis and detailed anatomic diagnosis, but also permits immediate post
      interventional, anatomical, and functional delineation of procedure success that
      may serve as a baseline for future comparison during follow-up.

PMID- 16431875
TI  - Long-term outcome with first-line bosentan therapy in idiopathic pulmonary
      arterial hypertension.
AB  - AIMS: Data on long-term efficacy of bosentan in unselected idiopathic pulmonary
      arterial hypertension (IPAH) patients are lacking. We aimed to describe the long
      term outcome of consecutive IPAH patients treated first-line with bosentan.
      METHODS AND RESULTS: A retrospective analysis of 103 consecutive New York Heart
      Association functional class III/IV IPAH patients treated with bosentan at our
      centre between November 1999 and May 2004 was performed. The 6-minute walk
      distance (6MWD) and haemodynamics were assessed at baseline and after 4 and 12
      months. Mean follow-up was 24+/-15 months. At 4 months, significant improvements
      in exercise capacity and haemodynamics were observed and persisted up to 1 year.
      Overall survival estimates were 90 and 87% and event-free status (survival
      without transplantation, prostanoid initiation, or hospitalization for right
      heart failure) estimates were 61 and 44% at 1 and 2 years, respectively. Forty
      five (44%) patients required prostanoid therapy during follow-up. The 6MWD and
      the right atrial pressure at baseline and the 6MWD, the increase in 6MWD, and the
      decrease in pulmonary resistance after 4 months of treatment were associated with
      long-term outcomes. CONCLUSION: In our series of consecutive IPAH patients
      treated with bosentan, improvements in exercise capacity and haemodynamics were
      similar to those observed in previous randomized trials. However, on the basis of
      local criteria, many patients required the addition of prostanoid therapy during
      follow-up.

PMID- 16431876
TI  - Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas'
      disease patients.
AB  - We present a cross-sectional analysis of the maturation and migratory properties
      of the memory CD8(+) T cell compartment, in relation to the severity of heart
      disease in individuals with chronic Trypanosoma cruzi infection removed from
      endemic areas for longer than 20 years. Subjects with none or mild heart
      involvement were more likely to mount T. cruzi-specific memory IFN-gamma
      responses than subjects with more advanced cardiac disease, and the T. cruzi
      specific CD8(+) T cell population was enriched in early-differentiated
      (CD27(+)CD28(+)) cells in responding individuals. In contrast, the frequency of
      CD27(+)CD28(+)CD8(+) T cells in the total memory CD8(+) T cell population
      decreases, as disease becomes more severe, while the proportion of fully
      differentiated memory (CD27(-)CD28(-)) CD8(+) T cells increases. The analysis of
      CCR7 expression revealed a significant increase in total effector/memory CD8(+) T
      cells (CD45RA(-)CCR7(-)) in subjects with mild heart disease as compared with
      uninfected controls. Altogether, these results are consistent with the hypothesis
      of a gradual clonal exhaustion in the CD8(+) T cell population, perhaps as a
      result of continuous antigenic stimulation by persistent parasites.

PMID- 16431877
TI  - Antigen dose governs the shaping of CTL repertoires in vitro and in vivo.
AB  - Although it is well established that antigen dose plays an important role in
      determining the quality of T cells induced in vitro, it has not well been
      determined whether antigen dose also affects T cell repertoires induced in vivo.
      This study demonstrates that variation of antigen doses in vivo as well as in
      vitro induce structurally and functionally different T cell repertoires. CTLs
      generated in vitro with a low antigen dose showed much higher T cell
      responsiveness than CTLs generated with a high antigen dose, and the two CTL
      populations employed different TCR Vbeta chains. This is most likely due to
      repertoire selection based on TCR affinity. The secondary in vivo responses with
      a high or low dose of antigen following the primary response raised with the same
      dose resulted in a reversed dominance pattern of two particular TCR Vbeta
      phenotypes. TCR affinity of these two T cell populations appeared different,
      suggesting avidity selection based on antigen availability. Indeed, they required
      a distinct level of antigen for maximal cytolytic function, implying a different
      functional avidity. These results suggest that antigen-specific T cell repertoire
      is substantially affected by the antigen dose employed in vivo as well as in
      vitro.

PMID- 16431878
TI  - Provider-specific report cards: a tool for health sector accountability in
      developing countries.
AB  - In most health care systems in most countries, providers are not adequately held
      accountable - by governments, purchasers, provider professional associations or
      civil society - for the quality of care. One approach to improve provider
      accountability that is being debated and implemented in a subset of developed
      countries and a smaller group of developing countries is provider-specific
      comparative performance reporting. This review discusses universal design options
      for report cards, summarizes the evidence base, presents developing country
      examples, reviews challenges and outlines implementation steps. The ultimate aim
      is to provoke thoughtful debate about if and how comparative performance
      reporting fits within a developing country's broader framework of strategies to
      promote quality of care.

PMID- 16431879
TI  - Inhibition of neuronal nitric oxide synthase reduces isoflurane MAC and motor
      activity even in nNOS knockout mice.
AB  - BACKGROUND: The glutamate-nitric oxide-cyclic GMP pathway has been identified as
      a potential target for volatile anaesthetic agents as acute inhibition of nitric
      oxide synthase (NOS) reduces the minimum alveolar concentration (MAC) in most
      animal studies. However, mice deficient in the type I NOS isoform (nNOS) are
      reported to have a similar MAC for isoflurane and are not affected by non-isoform
      specific inhibitors. METHODS: We determined whether the nNOS specific inhibitor,
      7-nitroindazole (7-NI), had an effect on isoflurane MAC and righting reflex (RRF)
      and investigated spontaneous motor activity in an open-field study in wild-type
      (WT) and knockout (KO) mice. RESULTS: 7-NI reduced isoflurane MAC and RRF in both
      WT and KO animals (all P<0.04). 7-NI profoundly reduced spontaneous motor
      activity in both the WT and KO animals in the open-field study as indicated by a
      reduction in the number of line crossings and rearings in both WT and KO mice
      (both P<0.001). CONCLUSION: We conclude that isoform specific inhibition of nNOS
      reduces MAC and spontaneous motor activity even in nNOS KO animals. Our results
      indicate that the NMDA receptor-nitric oxide-cyclic GMP pathway remains a
      credible target in modulating the effects of isoflurane.

PMID- 16431880
TI  - Large volume N2O uptake alone does not explain the second gas effect of N2O on
      sevoflurane during constant inspired ventilation.
AB  - BACKGROUND: The second gas effect (SGE) is considered to be significant only
      during periods of large volume N(2)O uptake (VN(2)O); however, the SGE of small
      VN(2)O has not been studied. We hypothesized that the SGE of N(2)O on sevoflurane
      would become less pronounced when sevoflurane administration is started 60 min
      after the start of N(2)O administration when VN(2)O has decreased to
      approximately 125 ml min(-1), and that the kinetics of sevoflurane under these
      circumstances would become indistinguishable from those when sevoflurane is
      administered in O(2). METHODS: Seventy-two physical status ASA I-II patients were
      randomly assigned to one of six groups (n=12 each). In the first four groups,
      sevoflurane (1.8% vaporizer setting) administration was started 0, 2, 5 and 60
      min after starting 2 litre min(-1) O(2) and 4 litre min(-1) N(2)O, respectively.
      In the last two groups, sevoflurane (1.8 or 3.6% vaporizer setting) was
      administered in 6 litre min(-1) O(2). The ratios of the alveolar fraction of
      sevoflurane (Fa) over the inspired fraction (Fi), or Fa/Fi, were compared between
      the groups. RESULTS: Sevoflurane Fa/Fi was larger in the N(2)O groups than in the
      O(2) groups, and it was identical in all four N(2)O groups. CONCLUSIONS: We
      confirmed the existence of a SGE of N(2)O. Surprisingly, when using an Fa of 65%
      N(2)O, the magnitude of the SGE was the same with large or small VN(2)O. The
      classical model and the graphical representation of the SGE alone should not be
      used to explain the magnitude of the SGE. We speculate that changes in
      ventilation/perfusion inhomogeneity in the lungs during general anaesthesia
      result in a SGE at levels of VN(2)O previously considered by most to be too small
      to exert a SGE.

PMID- 16431881
TI  - Repetitive paravertebral nerve block using a catheter technique for pain relief
      in post-herpetic neuralgia.
AB  - We described in this report a case of post-herpetic neuralgia refractory to
      medical therapy that was successfully treated with repetitive injections of local
      aesthetic mixture (bupivacaine 0.5% 19 ml and clonidine 150 microg ml(-1) 1 ml)
      every 48 h for 3 weeks using a paravertebral catheter inserted at T2-T3 level.

PMID- 16431882
TI  - Epidural abscesses.
AB  - Until recently epidural abscess was considered a rare, almost theoretical,
      complication of central nerve block, but anecdotal reports suggest that this is
      no longer the case. Thus a review of the risk factors, pathogenesis, clinical
      features and outcome of this condition is appropriate, the primary aim being to
      make recommendations on best anaesthetic practice to minimize the risk of this
      serious complication. A search of EMBASE(c), PUBMED(c) and MEDLINE(c) databases
      from 1966 to September 2004 was performed using several strategies, supplemented
      by reference list screening. Spontaneous epidural abscess is rare, accounting for
      0.2-1.2 cases per 10,000 hospital admissions per year. Estimates of the incidence
      after central nerve block vary from 1:1,000 to 1:100,000. Risk factors
      (compromised immunity, spinal column disruption, source of infection) are present
      in the majority of patients, whether the condition is spontaneous or associated
      with central nerve block. Presentation is vague, fever and back pain usually
      preceding neurological deficit. Diagnosis requires a high index of suspicion and
      modern imaging techniques. Treatment involves early surgical drainage to prevent
      permanent deficit and high dose parenteral antibiotics chosen with
      bacteriological advice. Primary prevention depends on proper use of full aseptic
      precautions. Epidural abscess can be a catastrophic consequence of central nerve
      block. Early diagnosis will minimize permanent damage, but primary prevention
      should be the aim. There is a need for a large survey to indicate the true
      incidence to better inform the risk-benefit ratio for central nerve block.

PMID- 16431883
TI  - Novel multiparameter approach for measurement of nociception at skin incision
      during general anaesthesia.
AB  - BACKGROUND: Direct indicators for the evaluation of the nociceptive-anti
      nociceptive balance during general anaesthesia do not exist. The aim of this
      study was to combine physiological parameters to obtain such an indicator.
      METHODS: Fifty-five females scheduled for surgery under general anaesthesia
      combining target-controlled infusions of propofol and remifentanil were studied.
      Propofol was given to maintain state entropy (SE) at 50 and remifentanil was
      targeted at 1, 3 or 5 ng ml(-1). The patients' reactions and clinical signs of
      nociception, remifentanil levels and estimation of noxious intensity of incision
      were combined into a clinical score [Clinical Signs-Stimulus-Antinociception
      (CSSA)] to evaluate the nociceptive-anti-nociceptive balance. ECG,
      photoplethysmography (PPG), response entropy (RE) and SE were recorded from 60 s
      before to 120 s after skin incision. Differences between post- and pre-incision
      values of heart rate variability (HRV), PPG and pulse transition time related
      parameters were analysed off-line to evidence the best predictors of CSSA. Those
      best predictors of CSSA served to develop a response index of nociception (RN),
      scaled from 0 to 100. This index was further tested in 10 additional patients.
      RESULTS: HRV, RE, RE-SE and PPG variability were the best predictors of CSSA. The
      prediction probability of RN at predicting CSSA was 0.78. RN response was higher
      after larger incision, in movers and with lower remifentanil concentrations.
      CONCLUSIONS: The empirically developed algorithm of RN leads to an index that
      seems to adequately estimate the nociceptive-anti-nociceptive balance at skin
      incision during general anaesthesia. In the future, CSSA may serve as a reference
      for studies investigating methods aimed at evaluating this pharmacodynamic
      component of anaesthesia.

PMID- 16431885
TI  - A nephrotic patient with tumour necrosis factor receptor-associated periodic
      syndrome, IgA nephropathy and CNS involvement.

PMID- 16431884
TI  - Characteristics of polyclonal anti-human nephrin antibodies induced by genetic
      immunization using nephrin cDNA.
AB  - BACKGROUND: Nephrin is an essential protein for maintaining the normal structure
      of the podocyte foot process and the glomerular filtration barrier. To analyse
      the mechanism of proteinuria and treatment of nephrotic syndrome, we produced and
      characterized polyclonal anti-human nephrin antibodies using a newly developed
      genetic immunization technique. METHODS: An expression vector with full-length or
      fragmented cDNA of human nephrin protein was administered to female Lewis rats
      once a week for 12 weeks using a gene-gun method. Antibody production against
      different fragments of nephrin protein was then analysed by ELISA, Western blot
      analysis, immunoprecipitation and FACS analysis. We also analysed recognition of
      native nephrin protein using immunohistochemistry and electron microscopy, and
      conducted a functional analysis of in vitro clustering of nephrin protein.
      RESULTS: Serum anti-nephrin antibody titers reached a maximum level at 8 or 12
      weeks. Four of five antibodies induced with cDNA of five different Ig-like motif
      fragments showed antigen-specific binding to Escherichia coli and produced
      recombinant human nephrin protein. Only two of these four antibodies, plus one
      antibody induced by full-length human nephrin protein cDNA, bound to solubilized
      native nephrin protein. These three IgG antibodies, subclasses IgG1, IgG2a and
      IgG2b, showed fine granular staining along the glomerular basement membrane of
      normal human glomeruli and clustering of human nephrin protein on plasma
      membranes of HEK293 cells. CONCLUSIONS: We successfully produced polyclonal anti
      human nephrin antibodies by genetic immunization using nephrin cDNA. These new
      antigen-specific polyclonal antibodies will be useful for functional analysis and
      tissue staining of native nephrin protein.

PMID- 16431886
TI  - Association of MEGSIN 2093C-2180T haplotype at the 3' untranslated region with
      disease severity and progression of IgA nephropathy.
AB  - BACKGROUND: MEGSIN is a gene predominantly expressed in the renal mesangium, and
      is upregulated in IgA nephropathy (IgAN). Our previous study has shown that the
      2093C and 2180T alleles at the 3' untranslated region (3'UTR) of the gene are
      associated with susceptibility to IgAN, but the relationships of these genetic
      variants with the clinical manifestations and renal histological lesions of IgAN
      have not been examined previously. METHODS: 302 IgAN patients followed up for
      52.8+/-22.5 months were investigated. Haplotypes at the 3'UTR were constructed
      using the 2093C/T and 2180C/T alleles. The genotype-phenotype relationship was
      studied by correlations of haplotypes and the clinical data and renal
      histopathological changes. RESULTS: The 2093C-2180T haplotype was present more
      often in patients with disease that progressed more rapidly (chi2((C-T/others)) =
      8.429, P = 0.004), and was also correlated with hypertension (chi2((C-T/others))
      = 6.459, P = 0.012), severe proteinuria (>or=2 g/d) (chi2((C-T/others)) = 6.332,
      P = 0.013), and Lee's class IV and V histological changes (chi2((C-T/others)) =
      9.640, P = 0.008). CONCLUSION: In this Chinese population, the 2093C-2180T
      haplotype at the 3'UTR of MEGSIN gene is associated with more severe forms of
      IgAN, and more rapid disease progression. This provides further evidence for the
      involvement of genetic variations of MEGSIN in the pathogenesis of IgAN.

PMID- 16431887
TI  - Association of the circulating adiponectin concentration with coronary in-stent
      restenosis in haemodialysis patients.
AB  - BACKGROUND: Success of coronary stenting is limited by in-stent restenosis. We
      aimed to determine whether circulating levels of the cytokines, which have anti
      inflammatory properties such as adiponectin or interleukin-10, could be
      associated with the occurrence of coronary in-stent restenosis in patients with
      end-stage renal disease (ESRD). METHODS: We enrolled 71 consecutive ESRD patients
      undergoing haemodialysis (mean age: 64.9+/-8.9 years; 19 women, 52 men; mean
      haemodialysis duration: 78.2+/-87.5 months), who received stenting for a single
      coronary lesion. Plasma concentrations of adiponectin and IL-10 were measured
      within one week before coronary stenting. RESULTS: Of the 71 patients who had
      received stenting, in-stent restenosis occurred in 37 patients (52.1%) within 6
      months after stenting. In univariate logistic analysis, the homeostasis model
      assessment index of insulin resistance, blood haemoglobin, serum concentrations
      of high density lipoprotein-cholesterol or triglycerides and plasma
      concentrations of insulin or adiponectin were significantly associated with
      coronary in-stent restenosis. In a multiple logistic regression analysis among
      these variables, however, only the plasma adiponectin concentration was
      associated with the coronary in-stent restenosis: the odds ratio of the increase
      in 1 microg/ml of plasma adiponectin concentration for having restenosis was
      0.651 (P = 0.001, 95% confidence interval: 0.506-0.839). Patients with restenosis
      had lower plasma adiponectin concentrations than those without [6.2+/-2.2
      microg/ml (2.1-10.4 microg/ml; n = 37) vs 27.2+/-10.8 microg/ml (17.9-79.8
      microg/ml; n = 34); P = 0.0001]. CONCLUSIONS: Circulating adiponectin
      concentrations may be associated with the occurrence of coronary in-stent
      restenosis in ESRD patients undergoing maintenance haemodialysis.

PMID- 16431888
TI  - Haematopoietic stem cell transplantation for severe autoimmune diseases: new
      perspectives.

PMID- 16431889
TI  - Rituximab-induced long-term remission of membranous lupus nephritis.

PMID- 16431890
TI  - Gadolinium--a specific trigger for the development of nephrogenic fibrosing
      dermopathy and nephrogenic systemic fibrosis?

PMID- 16431891
TI  - Rapidly progressive glomerulonephritis in a patient with brucellosis.

PMID- 16431892
TI  - An unusual case of dramatic acute bilateral pyelonephritis with systemic
      bacterial dissemination caused by uropathogenic Escherichia coli.

PMID- 16431893
TI  - A randomized trial comparing losartan with amlodipine as initial therapy for
      hypertension in the early post-transplant period.
AB  - BACKGROUND: Blockade of the renin-angiotensin-aldosterone system in the early
      post-transplant period remains controversial. Angiotensin II-receptor blockers
      (ARB) have many benefits to the patient with chronic kidney disease and these
      benefits may also apply to the renal transplant recipient (RTR). Additionally,
      there are theoretical benefits of ARB use in RTR. This study was designed to
      investigate the safety of early ARB use after renal transplantation. METHODS: RTR
      with serum creatinine levels <3.0 mg/dl were randomized to receive either ARB (n
      = 29) or calcium-channel blocker (CCB; n = 27) as initial therapy for post
      transplant hypertension. Differences in potassium, creatinine and haemoglobin
      concentrations were compared at baseline, 3, 6 and 12 months after
      transplantation. RESULTS: Withdrawal from the assigned treatment was high: 12 in
      the ARB group (due to hyperkalaemia in six) and 17 in the CCB group (due to
      intractable oedema in seven and post-transplant erythrocytosis requiring an
      angiotensin-converting enzyme inhibitor in seven). There were no differences in
      blood pressure, haemoglobin or creatinine concentration at any time-points. Mean
      potassium concentrations were only slightly higher in the ARB vs CCB group
      (range: 4.2-4.3 vs 3.7-3.8 mEq/l, respectively, but clinically significant) and
      the number of patients with potassium values >6.0 mEq/l was higher in ARB (n = 7)
      vs CCB (n = 1). CONCLUSIONS: These data suggest that hyperkalaemia is the major
      complication that occurs with the use of ARB in the immediate post-transplant
      period. ARB use does not affect renal function or complicate the post-transplant
      management of RTR. Other than reducing the incidence of post-transplant
      erythrocytosis, ARB use does not cause an excess incidence of anaemia. Strategies
      to reduce the risk of hyperkalaemia may allow increased use of ARB immediately
      after kidney transplantation.

PMID- 16431894
TI  - Novel anti-inflammatory drugs in hypertension.

PMID- 16431895
TI  - Does obesity play a role in the pathogenesis of calcific uraemic arteriolopathy?

PMID- 16431896
TI  - Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values
      and cell proliferation in azotemic rats.
AB  - BACKGROUND: A variety of stimuli are involved in the pathogenesis of parathyroid
      gland hyperplasia in renal failure. Recently, it was shown that blocking the
      signal from the endothelin-1 (ET-1) receptor (ET(A)R/ET(B)R) by a non-selective
      receptor antagonist, bosentan, reduced parathyroid cell proliferation,
      parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats
      on a calcium deficient diet. Our goal was to determine whether in 5/6
      nephrectomized (NPX) rats with developing or established hyperparathyroidism, the
      endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell
      proliferation, parathyroid gland hyperplasia and PTH values. METHODS: High (HPD,
      1.2%) or normal phosphorus diets (PD) (NPD, 0.6%) were given to 5/6 NPX rats for
      15 days (NPX(15)). In each dietary group, one-half the rats were given bosentan
      (B) i.p. 100 mg/kg/day. The four groups of rats were: (1) NPX(15)-1.2% P; (2)
      NPX(15)-1.2% P+B; (3) NPX(15)-0.6% P; and (4) NPX(15)-0.6% P+B. In a second study
      in which hyperparathyroidism was already established in 5/6 NPX rats fed a HPD
      for 15 days, rats were divided into two groups in which one group was maintained
      on a HPD and the other group was changed to very low PD (VLPD, <0.05%) for an
      additional 15 days. In each dietary group, one-half the rats were given bosentan
      i.p. 100 mg/kg-day. The four groups of rats were: (1) NPX(30)-1.2% P; (2) NPX(30)
      1.2% P+B; (3) NPX(30)-0.05% P and (4) NPX(30)-0.05% P+B. Parathyroid cell
      proliferation was measured by proliferating cell nuclear antigen (PCNA) staining
      and ET-1 expression by immunohistochemical techniques. RESULTS: In the study of
      developing hyperparathyroidism, bosentan reduced ET-1 expression in the
      parathyroid glands of rats on the NPD and HPD (P<0.05). But only in rats on the
      NPD did bosentan result in a reduced increase in parathyroid gland weight
      (P<0.05). In the study of established hyperparathyroidism, in which 5/6 NPX rats
      were given a HPD for 15 days, bosentan started on day 15 reduced (P<0.05) ET-1
      expression in rats maintained for 15 additional days on the HPD or the VLPD. On
      the VLPD, parathyroid gland weight was less (P<0.05) than that in rats on the HPD
      sacrificed at 15 or 30 days. Bosentan did not reduce parathyroid cell
      proliferation or parathyroid gland weight in rats maintained on the HPD or
      further reduce these parameters beyond that obtained with dietary phosphorus
      restriction. PTH values were lowest in the VLPD group, intermediate in the NPD
      group, and highest in the HPD group, but in none of the three groups did bosentan
      decrease PTH values. CONCLUSIONS: In azotemic rats with developing
      hyperparathyroidism, bosentan resulted in a reduced increase in parathyroid gland
      weight when dietary phosphorus content was normal. Despite a reduction in ET-1
      expression in rats on a HPD with developing or established hyperparathyroidism,
      bosentan did not reduce the increase in parathyroid cell proliferation,
      parathyroid gland growth or PTH values. Thus, ET-1 blockade with bosentan did not
      prevent parathyroid gland growth in the azotemic rat.

PMID- 16431897
TI  - A computerized photographic assessment of the relationship between skeletal
      discrepancy and mandibular outline asymmetry.
AB  - The aim of this study was to investigate the relationship between mandibular
      outline asymmetry and skeletal discrepancy in a sample of orthodontic patients
      (33 females, 33 males) aged from 8 to 19 years. Skeletal discrepancy was assessed
      in both the anteroposterior and vertical planes, using standard cephalometric
      analyses. All were photographed under standardized conditions and the photographs
      were then digitized for analysis using a computerized system to assess
      differences in four variables (area, perimeter, compactness and moment-ratio)
      between the right and left sides of the mandibular outline. The results showed
      good repeatability of the photographic, cephalometric and digitization methods. A
      statistically significant relationship was found between mandibular outline
      asymmetry and both anteroposterior and vertical skeletal discrepancy in this
      sample, when compared with patients with an average skeletal pattern. There
      appeared to be a statistically significant relationship between a reduced ANB
      angle (< 3 degrees) and mandibular outline asymmetry (P = 0.051), as well as
      between an increase in lower face height and mandibular asymmetry (P = 0.023).

PMID- 16431899
TI  - Effect of first-trimester serum from pregnant women with high-resistance uterine
      artery Doppler resistance on extravillous trophoblast invasion.
AB  - BACKGROUND: Abnormal uterine artery Doppler indices are associated with pregnancy
      complications such as pre-eclampsia and intrauterine growth restriction. Poor
      trophoblast invasion may be a consequence of, or be associated with, abnormal
      Doppler indices. OBJECTIVE: To evaluate in vitro trophoblast function following
      exposure to first-trimester serum from pregnancies with high uterine artery
      Doppler resistance indices. METHODS: Doppler ultrasound examination of the
      maternal uterine arteries was performed on women at 10-14 weeks' gestation. Serum
      was collected from women with bilateral uterine artery notches with resistance
      indices above the 95th centile and from patients with normal uterine artery
      indices. The effect of serum on trophoblast invasion was determined using an
      established in vitro model from the extravillous trophoblast-derived cell line
      SGHPL-4. RESULTS: Trophoblastic invasion was significantly reduced when treated
      with serum from women with high-resistance compared with normal-resistance
      uterine artery Doppler indices (P < 0.05). CONCLUSION: Maternal serum in the
      first trimester of pregnancy from patients with high-resistance uterine artery
      Doppler indices appears to inhibit trophoblast invasion. This experimental model
      allows further investigation of factors responsible and the evaluation of
      therapeutic strategies.

PMID- 16431898
TI  - A comparative study of cephalometric and arch width characteristics of Class II
      division 1 and division 2 malocclusions.
AB  - The aim of this compound cephalometric and arch-width study was to determine any
      dental and/or skeletal differences between subjects with Class II division 1 and
      Class II division 2 malocclusions. The dento-skeletal characteristics of Class II
      subjects were evaluated using lateral cephalometric radiographs and dental casts
      of 90 untreated patients. The sample included 46 Class II division 1 patients (19
      girls and 27 boys) with a mean age of 15.27 +/- 2.48 years, and 44 Class II
      division 2 patients (27 girls and 17 boys) with a mean age of 15.95 +/- 3.25
      years. The intermolar, interpremolar and intercanine measurements were carried
      out on study models. The radiographs were digitized and processed using Dolphin
      Imaging software. In addition to standard descriptive statistical calculations,
      an independent samples t-test was carried out in order to compare the two groups.
      The non-parametric Mann-Whitney U test was utilized for the parameters for the
      data which were not normally distributed. The only statistically significant
      difference between the groups for the study model measurements was mandibular
      intercanine width. The cephalometric results revealed that SNB angle was
      responsible for the skeletal sagittal difference between the two groups. In
      addition, the Class II division 1 group had higher vertical proportions and the
      Class II division 2 group a more concave profile with a prominent chin. The
      sagittal skeletal pattern of Class II division 2 subjects was found to be very
      similar to the Class I skeletal relationship, with no evidence of any mandibular
      restriction.

PMID- 16431901
TI  - Endometriosis and the risk of cancer with special emphasis on ovarian cancer.
AB  - BACKGROUND: Several observations of the coexistence of endometriosis and cancer
      have been published. One study concerning endometriosis patients from 1969 to
      1986 showed an overall relative cancer risk of 1.2 and relative risks for breast
      cancer, ovarian cancer and non-Hodgkin's lymphoma to be 1.3, 1.9 and 1.8,
      respectively. The aim of this study was to see whether these risk ratios stand in
      an extended study with longer follow-up. METHODS: Women discharged from a
      hospital, with a diagnosis of endometriosis from 1969 to 2000, were identified
      using the National Swedish Inpatient Register. Data were linked to the National
      Swedish Cancer Register to identify cases of cancer. Data on hysterectomies and
      oophorectomies were available. Standardized incidence ratios (SIR) were
      calculated. RESULTS: 64 492 women entered the study. First year of follow-up was
      excluded, leaving 3349 cases of cancer. There was no increased overall risk of
      cancer [SIR 1.04, 95% CI 1.00-1.07]. Elevated risks were found for ovarian cancer
      (SIR 1.43, 95% CI 1.19-1.71), endocrine tumours (SIR 1.36, 95% CI 1.15-1.61), non
      Hodgkin's lymphoma (SIR 1.24, 95% CI 1.02-1.49) and brain tumours (SIR 1.22, 95%
      CI 1.04-1.41). Women with early diagnosed and long-standing endometriosis had a
      higher risk of ovarian cancer, with SIR of 2.01 and 2.23, respectively. The
      average age at endometriosis diagnosis was 39.4, indicating that there are the
      moderate/severe cases that are included in this study. Women who had a
      hysterectomy before or at the time of the endometriosis diagnosis did not show an
      increased risk of ovarian cancer. CONCLUSION: Women with endometriosis have an
      increased risk of some malignancies, particularly ovarian cancer, and the risk
      increases with early diagnosed or long-standing disease. Hysterectomy may have a
      preventive effect against ovarian cancer.

PMID- 16431900
TI  - Genetic thrombophilic mutations among couples with recurrent miscarriage.
AB  - BACKGROUND: Some cases of recurrent first trimester miscarriage (RM)-the loss of
      three or more consecutive pregnancies at <12 weeks' gestation-have a thrombotic
      aetiology. METHODS: We determined (i) the prevalence of three thrombophilic
      mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and
      methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 357 Caucasian couples
      with RM and 68 parous Caucasian couples with no history of miscarriage and (ii)
      the prospective outcome of untreated pregnancies amongst couples with RM in which
      either partner carried a thrombophilic mutation. RESULTS: The allele frequencies
      of FVL (2%), PTG (2%) and MTHFR C677T (31%) were similar between cases and
      controls. The prevalence of multiple thrombophilic mutations (greater than one
      mutation) was also similar between cases and controls. Amongst couples in whom
      either partner carried greater than one thrombophilic allele, the relative risk
      of miscarriage in a future untreated pregnancy was 1.9 (95% confidence interval,
      1.3-2.8) compared with those couples who carried no thrombophilic mutation.
      CONCLUSION: The prevalence of thrombophilic mutations is similar in couples with
      RM and parous controls. In couples with RM, multiple genetic thrombophilic
      mutations in either partner significantly increases the risk of miscarriage in a
      subsequent pregnancy.

PMID- 16431902
TI  - Results of assisted reproductive technique in men with cystic fibrosis.
AB  - BACKGROUND: Sterility in men with cystic fibrosis (CF) raises the question of the
      use of assisted reproductive techniques (ART). A multidisciplinary network
      including adult CF centre and reproductive medicine units was set up to answer
      requests for ART. METHODS: This retrospective study included 25 men with CF
      between 1994 and 2004. Clinical status, semen analysis, CF mutations analysis and
      artificial insemination by donor (AID) or ICSI after surgical retrieval of sperm
      were monitored. RESULTS: All CF men had azoospermia. Two chose AID first (one
      delivery); 23 chose ICSI. Sperm were surgically retrieved in 21 cases, and ICSI
      was performed in 19. Pregnancies occurred in 12 of these 19 couples (63%) (two
      ectopic pregnancies, two spontaneous abortions, one termination of pregnancy for
      polymalformed twins and 11 single deliveries in nine couples). Two couples tried
      AID after ICSI failed; one had twins. Another adopted a child, and two had a
      spontaneous pregnancy. After a follow-up of 4.1+/-2.3 years, two patients died,
      two underwent lung transplantation and 21 remained stable. CONCLUSION: ART can
      help men with CF to become a father, but their health status and short survival
      need careful counselling and multidisciplinary medical care.

PMID- 16431903
TI  - Chemokine CXCL16, a scavenger receptor, induces proliferation and invasion of
      first-trimester human trophoblast cells in an autocrine manner.
AB  - BACKGROUND: The aim of this study was to investigate whether CXCL16/CXCR6, a
      newly identified chemokine pair, is expressed in first-trimester human placenta
      and whether they affect the trophoblast cell biology, since we have found CXCR6
      highly transcribed in first-trimester human trophoblast cells previously.
      METHODS: We analysed the transcription and translation of CXCR6 and CXCL16 in
      purified first-trimester human trophoblast cells by real-time RT-PCR and
      immunochemical staining. We then examined the kinetic secretion of CXCL16 in the
      supernatant of primary-cultured trophoblast by enzyme-linked immunosorbent assay.
      We further investigated effects of CXCL16 on the proliferation and invasion of
      trophoblast cells in vitro. RESULTS: We found the chemokine pair CXCL16/CXCR6 was
      transcribed and translated in first-trimester trophoblast cells and JAR line. In
      addition, the primary-cultured trophoblasts secreted CXCL16 spontaneously and
      continuously in 100-h culture. Treating trophoblasts with CXCL16 induced marked
      proliferation and invasion in vitro. CONCLUSION: The findings from this study
      have demonstrated for the first time that CXCR6 and CXCL16 are co-expressed by
      first-trimester human trophoblast cells and stimulate their proliferation and
      invasion in an autocrine/paracrine manner. It suggests that CXCL16 plays
      important roles in human extravillous cytotrophoblast invasion and placentation.

PMID- 16431905
TI  - The kinetic mechanism of the SufC ATPase: the cleavage step is accelerated by
      SufB.
AB  - Protein products of the suf operon are involved in iron-sulfur metabolism. SufC
      is an ATPase that can interact with SufB in the absence of nucleotide. We have
      studied the transient kinetics of the SufC ATPase mechanism using the fluorescent
      ATP analogue, 2'(3')-O-N-methylanthraniloyl-ATP (mantATP). mantATP initially
      binds to SufC weakly. A conformational change of the SufC.mantATP complex then
      occurs followed by the very slow cleavage of mantATP to mantADP and the rapid
      release of Pi. In the presence of SufB, the cleavage step is accelerated and the
      release of mantADP is inhibited. Both of these effects promote the formation of a
      SufC.mantADP complex. In the absence and presence of SufB, mantADP remains more
      tightly bound to SufC than mantATP. These studies provide a basis for how the
      SufB and -C proteins interact in the processes involved in regulating iron-sulfur
      transfer.

PMID- 16431906
TI  - Polyamines are potent ligands for the capsaicin receptor TRPV1.
AB  - Polyamines are important endogenous regulators of ion channels and are known to
      modulate inflammation and nociception. Here we investigated effects of polyamines
      on the capsaicin receptor TRPV1, a major ion channel expressed in nociceptive
      sensory afferents. Extracellular spermine, spermidine, and putrescine directly
      activated TRPV1 in a charge-dependent manner, both in heterologous expression
      systems and sensory neurons. The threshold for activation by spermine was
      approximately 500 microm at room temperature. At lower concentrations, spermine
      enhanced capsaicin-evoked currents with an EC50 of approximately 5 microm.
      Further, polyamines freely permeated TRPV1 (estimated relative permeabilities
      compared with Na+ were between 3 and 16), and spermine reduced the single channel
      conductance from 96 to 49 pS. Experiments with TRPV1 mutants identified
      extracellular acidic residues critical for polyamine regulation. Neutralization
      of aspartate 646 (D646N) abolished direct activation by spermine, whereas
      neutralization of this same aspartate (D646N) or glutamate 648 (E648A) inhibited
      spermine-induced sensitization. These data show that polyamines, by virtue of
      their cationic charge, can regulate the activity of TRPV1. Extracellular
      polyamines are present in considerable concentrations in the gastrointestinal
      tract and at synapses, and these levels increase during inflammation and cancer.
      Therefore, polyamine regulation of TRPV1 in these tissues may be relevant to a
      variety of physiological and pathophysiological states.

PMID- 16431904
TI  - GAP1 family members constitute bifunctional Ras and Rap GTPase-activating
      proteins.
AB  - GAP1(IP4BP) is a member of the GAP1 family of Ras GTPase-activating proteins (Ras
      GAPs) that includes GAP1(m), CAPRI, and RASAL. Composed of a central Ras GAP
      domain, surrounded by amino-terminal C(2) domains and a carboxyl-terminal
      pleckstrin homology/Bruton's tyrosine kinase domain, GAP1(IP4BP) has previously
      been shown to possess an unexpected GAP activity on the Ras-related protein Rap,
      besides the predicted Ras GAP activity (Cullen, P. J., Hsuan, J. J., Truong, O.,
      Letcher, A. J., Jackson, T. R., Dawson, A. P., and Irvine, R. F. (1995) Nature
      376, 527-530). Here we have shown that GAP1(IP4BP) is indeed an efficient Ras/Rap
      GAP, having K(m)s of 213 and 42 microm and estimated k(cat)s of 48 and 16 s(-1)
      for Ras and Rap, respectively. For this dual activity, regions outside the Ras
      GAP domain are required, as the isolated domain (residues 291-569) retains a
      pronounced Ras GAP activity yet has very low activity toward Rap. Interestingly,
      mutagenesis of the Ras GAP arginine finger, and surrounding residues important in
      Ras binding, inhibit both Ras and Rap GAP activity of GAP1(IP4BP). Although the
      precise details by which GAP1(IP4BP) can function as a Rap GAP remain to be
      determined, these data are consistent with Rap associating with GAP1(IP4BP)
      through the Ras-binding site within the Ras GAP domain. Finally, we have
      established that such dual Ras/Rap GAP activity is not restricted to GAP1(IP4BP).
      Although GAP1(m) appears to constitute a specific Ras GAP, CAPRI and RASAL
      display dual activity. For CAPRI, its Rap GAP activity is modulated upon its
      Ca(2+)-induced association with the plasma membrane.

PMID- 16431907
TI  - Substrate preferences of the EZH2 histone methyltransferase complex.
AB  - Histone methylation plays an important role in chromatin dynamics and gene
      expression. Methylation of histone H3-lysine 27 by the EZH2 complex has been
      linked to the silencing of homeotic genes and the inactivation of the X
      chromosome. Here we report a characterization of the substrate preferences of the
      enzyme complex using a reconstituted chromatin and enzyme system. We found that
      the linker histone H1, when incorporated into nucleosomes, stimulates the
      enzymatic activity toward histone H3. This stimulatory activity may be explained
      by protein-protein interactions between H1 and components of the EZH2 complex. In
      addition, we found that the EZH2 complex exhibits a dramatic preference for
      dinucleosomes when compared with mononucleosomes and that the stimulation of H3
      methylation by H1 requires dinucleosomes or oligonucleosome substrates.
      Furthermore, in contrast with a recent study suggesting that Embryonic Ectoderm
      Development EED isoforms may affect substrate specificity, we found that EZH2
      complexes reconstituted with different EED isoforms exhibit similar substrate
      preference and specificity. Our work supports the hypothesis that linker histone
      H1 and chromatin structure are important factors in determining the substrate
      preference of the EZH2 histone methyltransferase complex.

PMID- 16431909
TI  - The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the
      scaffold protein Isu1p.
AB  - The specialized yeast mitochondrial chaperone system, composed of the Hsp70
      Ssq1p, its co-chaperone J-protein Jac1p, and the nucleotide release factor Mge1p,
      perform a critical function in the biogenesis of iron-sulfur (Fe/S) proteins.
      Using a spectroscopic assay, we have analyzed the potential role of the
      chaperones in Fe/S cluster assembly on the scaffold protein Isu1p in vitro in the
      presence of the cysteine desulfurase Nfs1p. In the absence of chaperones, the
      kinetics of Fe/S cluster formation on Isu1p were compatible with a chemical
      reconstitution pathway with Nfs1p functioning as a sulfide donor. Addition of
      Ssq1p improved the rates of Fe/S cluster assembly 3-fold. However, this
      stimulatory effect of Ssq1p required neither ATP nor Jac1p and could be fully
      attributed to the activation of the Nfs1p desulfurase activity by Ssq1p.
      Furthermore, chaperone-stimulated Fe/S cluster assembly did not involve the
      specific interaction between Isu1p and Ssq1p, since the effect was observed with
      Isu1p mutant proteins defective in this interaction, suggesting that nonspecific
      binding of Ssq1p to Nfs1p helped to prevent its unfolding. Consistent with this
      idea, these Isu1p mutants were capable of binding an Fe/S cluster in vivo but
      failed to restore the growth and Fe/S cluster assembly defects of a Isu1p/Isu2p
      deficient yeast strain. Taken together, these data suggest that Ssq1p/Jac1p/Mge1p
      are not important for Fe/S cluster synthesis on Isu1p. Hence, consistent with
      previous in vivo data, these chaperones likely function in steps subsequent to
      the de novo synthesis of the Fe/S cluster on Isu1p.

PMID- 16431910
TI  - Rapid activation of ATR by ionizing radiation requires ATM and Mre11.
AB  - The ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein
      kinases are crucial regulatory proteins in genotoxic stress response pathways
      that pause the cell cycle to permit DNA repair. Here we show that Chk1
      phosphorylation in response to hydroxyurea and ultraviolet radiation is ATR
      dependent and ATM- and Mre11-independent. In contrast, Chk1 phosphorylation in
      response to ionizing radiation (IR) is dependent on ATR, ATM, and Mre11. The ATR
      and ATM/Mre11 pathways are generally thought to be separate with ATM activation
      occurring early and ATR activation occurring as a late response to double strand
      breaks. However, we demonstrate that ATR is activated rapidly by IR, and ATM and
      Mre11 enhance ATR signaling. ATR-ATR-interacting protein recruitment to double
      strand breaks is less efficient in the absence of ATM and Mre11. Furthermore, IR
      induced replication protein A foci formation is defective in ATM- and Mre11
      deficient cells. Thus, ATM and Mre11 may stimulate the ATR signaling pathway by
      converting DNA damage generated by IR into structures that recruit and activate
      ATR.

PMID- 16431911
TI  - Structure and activity of two metal ion-dependent acetylxylan esterases involved
      in plant cell wall degradation reveals a close similarity to peptidoglycan
      deacetylases.
AB  - The enzymatic degradation of plant cell wall xylan requires the concerted action
      of a diverse enzymatic syndicate. Among these enzymes are xylan esterases, which
      hydrolyze the O-acetyl substituents, primarily at the O-2 position of the xylan
      backbone. All acetylxylan esterase structures described previously display a
      alpha/beta hydrolase fold with a "Ser-His-Asp" catalytic triad. Here we report
      the structures of two distinct acetylxylan esterases, those from Streptomyces
      lividans and Clostridium thermocellum, in native and complex forms, with x-ray
      data to between 1.6 and 1.0 A resolution. We show, using a novel linked assay
      system with PNP-2-O-acetylxyloside and a beta-xylosidase, that the enzymes are
      sugar-specific and metal ion-dependent and possess a single metal center with a
      chemical preference for Co2+. Asp and His side chains complete the catalytic
      machinery. Different metal ion preferences for the two enzymes may reflect the
      surprising diversity with which the metal ion coordinates residues and ligands in
      the active center environment of the S. lividans and C. thermocellum enzymes.
      These "CE4" esterases involved in plant cell wall degradation are shown to be
      closely related to the de-N-acetylases involved in chitin and peptidoglycan
      degradation (Blair, D. E., Schuettelkopf, A. W., MacRae, J. I., and Aalten, D. M.
      (2005) Proc. Natl. Acad. Sci. U. S. A., 102, 15429-15434), which form the NodB
      deacetylase "superfamily."

PMID- 16431913
TI  - The GTP-binding protein YlqF participates in the late step of 50 S ribosomal
      subunit assembly in Bacillus subtilis.
AB  - Bacillus subtilis YlqF belongs to the Era/Obg subfamily of small GTP-binding
      proteins and is essential for bacterial growth. Here we report that YlqF
      participates in the late step of 50 S ribosomal subunit assembly. YlqF was co
      fractionated with the 50 S subunit, depending on the presence of noncleavable GTP
      analog. Moreover, the GTPase activity of YlqF was stimulated specifically by the
      50 S subunit in vitro. Dimethyl sulfate footprinting analysis disclosed that YlqF
      binds to a unique position in 23 S rRNA. Yeast two-hybrid data revealed
      interactions between YlqF and the B. subtilis L25 protein (Ctc). The interaction
      was confirmed by the pull-down assay of the purified proteins. Specifically, YlqF
      is positioned around the A-site and P-site on the 50 S subunit. Proteome analysis
      of the abnormal 50 S subunits that accumulated in YlqF-depleted cells showed that
      L16 and L27 proteins, located near the YlqF-binding domain, are missing. Our
      results collectively indicate that YlqF will organize the late step of 50 S
      ribosomal subunit assembly.

PMID- 16431912
TI  - Val-407 and Ile-408 in the beta5'-loop of pancreatic lipase mediate lipase
      colipase interactions in the presence of bile salt micelles.
AB  - In a previous study, we demonstrated that the beta5'-loop in the C-terminal
      domain of human pancreatic triglyceride lipase (hPTL) makes a major contribution
      in the function of hPTL (Chahinian et al. (2002) Biochemistry 41, 13725-13735).
      In the present study, we characterized the contribution of three residues in the
      beta5'-loop, Val-407, Ile-408, and Leu-412, to the function of hPTL. By
      substituting charged residues, aspartate or lysine, in these positions, we
      altered the hydrophilic to lipophilic ratio of the beta5'-loop. Each of the
      mutants was expressed, purified, and characterized for activity and binding with
      both monolayers and emulsions and for binding to colipase. Experiments with
      monolayers and with emulsions suggested that the interaction of hPTL with a
      phospholipid monolayer differs from the interaction of the hPTL-colipase complex
      with a dicaprin monolayer or a triglyceride emulsion (i.e. neutral lipids). Val
      407, Ile-408, and Leu-412 make major contributions to interactions with
      monolayers, whereas only Val-407 and Ile-408 appear essential for activity on
      triglyceride emulsions in the presence of bile salt micelles. In solutions of
      taurodeoxycholate at micellar concentrations, a major effect of the beta5'-loop
      mutations is to change the interaction between hPTL and colipase. These
      observations support a major contribution of residues in the beta5'-loop in the
      function of hPTL and suggest that a third partner, bile salt micelles or the
      lipid interface or both, influence the binding of colipase and hPTL through
      interactions with the beta5'-loop.

PMID- 16431915
TI  - EDEM3, a soluble EDEM homolog, enhances glycoprotein endoplasmic reticulum
      associated degradation and mannose trimming.
AB  - Quality control in the endoplasmic reticulum ensures that only properly folded
      proteins are retained in the cell through mechanisms that recognize and discard
      misfolded or unassembled proteins in a process called endoplasmic reticulum
      associated degradation (ERAD). We previously cloned EDEM (ER degradation
      enhancing alpha-mannosidase-like protein) and showed that it accelerates ERAD of
      misfolded glycoproteins. We now cloned mouse EDEM3, a soluble homolog of EDEM.
      EDEM3 consists of 931 amino acids and has all the signature motifs of Class I
      alpha-mannosidases (glycosyl hydrolase family 47) in its N-terminal domain and a
      protease-associated motif in its C-terminal region. EDEM3 accelerates
      glycoprotein ERAD in transfected HEK293 cells, as shown by increased degradation
      of misfolded alpha1-antitrypsin variant (null (Hong Kong)) and of TCRalpha.
      Overexpression of EDEM3 also greatly stimulates mannose trimming not only from
      misfolded alpha1-AT null (Hong Kong) but also from total glycoproteins, in
      contrast to EDEM, which has no apparent alpha1,2-mannosidase activity.
      Furthermore, overexpression of the E147Q EDEM3 mutant, which has the mutation in
      one of the conserved acidic residues essential for enzyme activity of alpha1,2
      mannosidases, abolishes the stimulation of mannose trimming and greatly decreases
      the stimulation of ERAD by EDEM3. These results show that EDEM3 has alpha1,2
      mannosidase activity in vivo, suggesting that the mechanism whereby EDEM3
      accelerates glycoprotein ERAD is different from that of EDEM.

PMID- 16431914
TI  - Leucine motif-dependent tyrosine autophosphorylation of type III receptor
      tyrosine kinases.
AB  - Activation loop tyrosine autophosphorylation is an essential requirement for full
      kinase activation of receptor tyrosine kinases (RTKs). However, mechanisms
      involved are not fully understood. In general, kinase domains of RTKs are folded
      into two main lobes, NH2- and COOH-terminal lobes. The COOH-terminal lobe of
      vascular endothelial growth factor receptor-2 (VEGFR-2) is folded into seven
      alpha-helices (alphaD-alphaI). In the studies presented here we demonstrate that
      leucine residues of helix I (alphaI) regulate tyrosine autophosphorylation and
      phosphotransferase activity of VEGFR-2. The presence of leucines 1158, 1161, and
      1162 are essential for tyrosine autophosphorylation and kinase activation of
      VEGFR-2 and are involved in helix-helix packing via hydrophobic interactions. The
      presence of leucine 1158 is critical for kinase activation of VEGFR-2 and appears
      to interact with alphaE, alphaF, alphaH, and beta7. The analogous residue,
      leucine 957 on platelet-derived growth factor receptor-beta and leucine 910 on
      colony stimulating factor-1R are also found to be critical for tyrosine
      autophosphorylation of these receptors. Leucines 1161 and 1162 are also involved
      in helix-helix packing but they play a less critical role in VEGFR-2 activation.
      Thus, we conclude that leucine motif-mediated helix-helix interactions are
      critical for kinase regulation of type III RTKs. This mechanism is likely to be
      shared with other kinases and might provide a basis for the design of a novel
      class of tyrosine kinase inhibitors.

PMID- 16431917
TI  - Enhancement of streptolysin O activity and intrinsic cytotoxic effects of the
      group A streptococcal toxin, NAD-glycohydrolase.
AB  - Streptolysin O (SLO) is a cholesterol-dependent cytolysin produced by the
      important human pathogen, group A Streptococcus (Streptococcus pyogenes or GAS).
      In addition to its cytolytic activity, SLO mediates the translocation of GAS NAD
      glycohydrolase (NADase) into human epithelial cells in vitro. Production of both
      NADase and SLO is associated with augmented host cell injury beyond that produced
      by SLO alone, but the mechanism of enhanced cytotoxicity is not known. We have
      now shown that expression of NADase together with SLO dramatically enhanced the
      lytic activity of GAS culture supernatants for erythrocytes but had no effect on
      SLO-mediated poration of synthetic cholesterol-rich liposomes. This result
      revealed a previously unknown contribution of NADase to the cytolytic activity
      associated with GAS production of SLO. Purified recombinant SLO bound NADase in
      vitro, supporting a specific, physical interaction of the two proteins. Exposure
      of human keratinocytes to wild-type GAS, but not to a NADase-deficient mutant
      strain, resulted in profound depletion of cellular NAD+ and ATP. Furthermore,
      expression of recombinant GAS NADase in yeast, in the absence of SLO, induced
      growth arrest, depletion of NAD+ and ATP, and cell death. These findings have
      provided evidence that the augmentation of SLO-mediated cytotoxicity by NADase is
      a consequence of depletion of host cell energy stores through the enzymatic
      action of NADase. Together, the results have provided mechanistic insight into
      the cytotoxic effects of a unique bipartite bacterial toxin.

PMID- 16431916
TI  - Rapid degradation of Bim by the ubiquitin-proteasome pathway mediates short-term
      ischemic tolerance in cultured neurons.
AB  - A previous exposure to a non-harmful ischemic insult (preconditioning) protects
      the brain against subsequent harmful ischemia (ischemic tolerance). In contrast
      to delayed gene-mediated ischemic tolerance, little is known about the molecular
      mechanisms that regulate rapid ischemic tolerance, which occurs within 1 h
      following preconditioning. Here we have investigated the degradation of the pro
      apoptotic Bcl-2 family member Bim as a mechanism of rapid ischemic tolerance. Bim
      protein levels were reduced 1 h following preconditioning and occurred concurrent
      with an increase in Bim ubiquitination. Ubiquitinated proteins are degraded by
      the proteasome, and inhibition of the proteasome with MG132 (a proteasome
      inhibitor) prevented Bim degradation and blocked rapid ischemic tolerance.
      Inhibition of p42/p44 mitogen-activated protein kinase activation by U0126
      reduced Bim ubiquitination and Bim degradation and blocked rapid ischemic
      tolerance. Finally, inhibition of Bim expression using antisense oligonucleotides
      also reduced cell death following ischemic challenge. Our results suggest that
      following preconditioning ischemia, Bim is rapidly degraded by the ubiquitin
      proteasome system, resulting in rapid ischemic tolerance. This suggests that the
      rapid degradation of cell death-promoting proteins by the ubiquitin-proteasome
      pathway may represent a novel therapeutic strategy to reduce cell damage
      following neuropathological insults, e.g. stroke.

PMID- 16431918
TI  - Role of Hirudin-like factor Va heavy chain sequences in prothrombinase function.
AB  - Proexosite I on prothrombin has been implicated in providing a recognition site
      for factor Va within prothrombinase. To examine whether hirudin-like sequences
      (659-698) on the cofactor contribute to this interaction, we expressed and
      purified two-chain FVa derivatives that were intracellularly truncated at the C
      terminus of the heavy chain: FVa709 (des710-1545), FVa699 (des700-1545), FVa(692
      (des693-1545), FVa678 (des679-1545), and FVa658 (des659-1545). We found that
      FVa709, FVa699, FVa692, and FVa678 exhibited specific clotting activities that
      were comparable with plasma-derived and recombinant FVa. Additionally, kinetic
      studies using prothrombin revealed that the Km and kcat values for these
      derivatives were unaltered. Fluorescent measurements and chromatography studies
      indicated that FVa709, FVa699, FVa692, and FVa678 bound to FXa membranes and
      thrombin-agarose in a manner that was comparable with the wild-type cofactors. In
      contrast, FVa658 had an approximately 1% clotting activity and reduced affinity
      for FXa membranes (approximately 20-fold) and did not bind to thrombin-agarose.
      Surprisingly, however, FVa(658) exhibited essentially normal kinetic parameters
      for prothrombin when the variant was fully saturated with FXa membranes. Overall
      our results are consistent with the interpretation that any possible binding
      interactions between prothrombin and the C-terminal region of the FVa heavy chain
      do not contribute in a detectable way to the enhanced function of prothrombinase.

PMID- 16431919
TI  - Redundancy of non-AUG initiators. A clever mechanism to enhance the efficiency of
      translation in yeast.
AB  - It was recently shown that ALA1, the only alanyl-tRNA synthetase gene in
      Saccharomyces cerevisiae, uses two successive ACG triplets as the translation
      initiators for its mitochondrial form. Evidence presented here argues that the
      second ACG triplet not only acts as a remedial initiation site for scanning
      ribosomes that skip the first ACG, but also enhances the activity of the
      preceding initiator by providing a preferable "A" at its relative position +4.
      Therefore, ALA1 constructs with redundant ACG initiators exhibit stronger
      complementing activity and express a higher level of protein than do those with a
      single ACG initiator. A similar scenario is seen when a single or redundant ACG
      triplets are placed in the positions of the first and second AUG initiators of
      VAS1, which serve as the start sites of the mitochondrial and cytoplasmic forms
      of valyl-tRNA synthetase, respectively. Cumulatively, the results suggest that
      this feature of redundancy of non-AUG initiators in a single mRNA per se may
      represent a novel paradigm for improving the efficiency of a poor or otherwise
      nonproductive initiation event.

PMID- 16431921
TI  - Intracellular zinc release and ERK phosphorylation are required upstream of 12
      lipoxygenase activation in peroxynitrite toxicity to mature rat oligodendrocytes.
AB  - Peroxynitrite toxicity has been implicated in the pathogenesis of white matter
      injury. The mechanisms of peroxynitrite toxicity to oligodendrocytes (OLs), the
      major cell type of the white matter, are unknown. Using primary cultures of
      mature OLs that express myelin basic protein, we found that 3
      morpholinosydnonimine, a peroxynitrite generator, caused toxicity to OLs.
      N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine, a zinc chelator, completely
      blocked peroxynitrite-induced toxicity. Use of FluoZin-3, a specific fluorescence
      zinc indicator, demonstrated the liberation of zinc from intracellular stores by
      peroxynitrite. Peroxynitrite caused the sequential activation of extracellular
      signal-regulated kinase 42/44 (ERK42/44), 12-lipoxygenase, and generation of
      reactive oxygen species, which were all dependent upon the intracellular release
      of zinc. The same cell death pathway was also activated when exogenous zinc was
      used. These results suggest that in addition to preventing the formation of
      peroxynitrite, useful strategies in preventing disease progression in pathologies
      in which peroxynitrite toxicity plays a critical role might include maintaining
      intracellular zinc homeostasis, blocking phosphorylation of ERK42/44, inhibiting
      activation of 12-lipoxygenase, and eliminating the accumulation of reactive
      oxygen species.

PMID- 16431920
TI  - Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP
      beta during adipogenesis requires a peroxisome proliferator-activated receptor
      gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter.
AB  - Studies have shown that CCAAT/enhancer-binding protein beta (C/EBP beta) can
      stimulate adipogenesis in noncommitted fibroblasts by activating expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma). Other
      investigations have established a role for C/EBP alpha as well as PPARgamma in
      orchestrating the complex program of adipogenic gene expression during terminal
      preadipocyte differentiation. Consequently, it is important to identify factors
      regulating transcription of the C/ebp alpha gene. In this study, we demonstrated
      that inhibition of PPARgamma activity by exposure of 3T3-L1 preadipocytes to a
      potent and selective PPARgamma antagonist inhibits adipogenesis but also blocks
      the activation of C/EBP alpha expression at the onset of differentiation. Ectopic
      expression of C/EBP beta in Swiss 3T3 mouse fibroblasts (Swiss-LAP cells) induces
      PPARgamma expression without any significant enhancement of C/EBP alpha
      expression. Treatment of Swiss-LAP cells with a PPARgamma agonist induces
      adipogenesis, which includes activation of C/EBP alpha expression. To further
      establish a role for PPARgamma in regulating C/EBP alpha expression, we expressed
      C/EBP beta in PPARgamma-deficient mouse embryo fibroblasts (MEFs). The data show
      that C/EBP beta is capable of inducing PPARgamma in Ppar gamma+/- MEFs, which
      leads to activation of adipogenesis, including C/EBP alpha expression following
      exposure to a PPARgamma ligand. In contrast, C/EBP beta is not able to induce
      C/EBP alpha expression or adipogenesis in Ppar gamma-/- MEFs. Chromatin
      immunoprecipitation analysis reveals that C/EBP beta is bound to the minimal
      promoter of the C/ebp alpha gene in association with HDAC1 in unstimulated Swiss
      LAP cells. Exposure of the cells to a PPARgamma ligand dislodges HDAC1 from the
      proximal promoter of the C/ebp alpha gene, which involves degradation of HDAC1 in
      the 26 S proteasome. These data suggest that C/EBP beta activates a single
      unified pathway of adipogenesis involving its stimulation of PPARgamma
      expression, which then activates C/EBP alpha expression by dislodging HDAC1 from
      the promoter for degradation in the proteasome.

PMID- 16431922
TI  - GEC1 interacts with the kappa opioid receptor and enhances expression of the
      receptor.
AB  - We identified a truncated form (38-117) of GEC1 that interacts with the C-tail of
      the human kappa opioid receptor (hKOR) by yeast two-hybrid screening. GEC1-(38
      117) did not interact with the C-tail of the mu or delta opioid receptors. GEC1,
      a 117-amino acid protein (Pellerin, I., Vuillermoz, C., Jouvenot, M., Ordener,
      C., Royez, M., and Adessi, G. L. (1993) Mol. Cell Endocrinol. 90, R17-R21), is
      highly homologous to GABARAP, GATE-16, and Apg8/aut7, all members of the
      microtubule associated protein (MAP) family. In pull-down assays, GST-GEC1
      interacted directly with the hKOR C-tail, full-length hKOR, and tubulin. When
      expressed in Chinese hamster ovary (CHO) cells, GEC1 co-immunoprecipitated with
      FLAG-hKOR. Expression of GEC1 greatly increased total and cell-surface KOR but
      not mu or delta opioid receptors. GEC1 expression slightly reduced U50,488H
      promoted down-regulation, without affecting ligand binding affinity, receptor-G
      protein coupling, or U50,488H-induced desensitization and internalization. HA
      GEC1 expressed in CHO cells was localized in the Golgi apparatus and endoplasmic
      reticulum (ER). When cells were pulsed with [35S]Met/Cys, GEC1 expression
      enhanced the level of the mature form (55-kDa band) of FLAG-hKOR at 4, 8, and 22
      h after pulse without affecting the precursors (39- and 45-kDa bands), indicating
      that GEC1 facilitates trafficking of FLAG-hKOR from the ER/Golgi to plasma
      membranes. GEC1 interacted with N-ethylmaleimide-sensitive factor (NSF) in pull
      down assays and co-immunoprecipitated with NSF in rat brain extracts. The
      interaction with NSF may contribute to GEC1 effects. This is the first report on
      biological functions of GEC1 and the first demonstration that a GPCR interacts
      with a protein of the MAP family. The interaction is important for trafficking of
      the receptor in the biosynthesis pathway.

PMID- 16431923
TI  - The nucleocapsid protein of severe acute respiratory syndrome-coronavirus
      inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S
      phase progression in mammalian cells.
AB  - Deregulation of the cell cycle is a common strategy employed by many DNA and RNA
      viruses to trap and exploit the host cell machinery toward their own benefit. In
      many coronaviruses, the nucleocapsid protein (N protein) has been shown to
      inhibit cell cycle progression although the mechanism behind this is poorly
      understood. The N protein of severe acute respiratory syndrome-coronavirus (SARS
      CoV) bears signature motifs for binding to cyclin and phosphorylation by cyclin
      dependent kinase (CDK) and has recently been reported by us to get phosphorylated
      by the cyclin-CDK complex (Surjit, M., Kumar, R., Mishra, R. N., Reddy, M. K.,
      Chow, V. T., and Lal, S. K. (2005) J. Virol. 79, 11476-11486). In the present
      study, we prove that the N protein of SARS-CoV can inhibit S phase progression in
      mammalian cell lines. N protein expression was found to directly inhibit the
      activity of the cyclin-CDK complex, resulting in hypophosphorylation of
      retinoblastoma protein with a concomitant down-regulation in E2F1-mediated
      transactivation. Coexpression of E2F1 under such conditions could restore the
      expression of S phase genes. Analysis of RXL and CDK phosphorylation mutant N
      protein identified the mechanism of inhibition of CDK4 and CDK2 activity to be
      different. Whereas N protein could directly bind to cyclin D and inhibit the
      activity of CDK4-cyclin D complex; inhibition of CDK2 activity appeared to be
      achieved in two different ways: indirectly by down-regulation of protein levels
      of CDK2, cyclin E, and cyclin A and by direct binding of N protein to CDK2-cyclin
      complex. Down-regulation of E2F1 targets was also observed in SARS-CoV-infected
      VeroE6 cells. These data suggest that the S phase inhibitory activity of the N
      protein may have major significance during viral pathogenesis.

PMID- 16431924
TI  - Versican G3 domain promotes blood coagulation through suppressing the activity of
      tissue factor pathway inhibitor-1.
AB  - We have detected versican, a member of the large chondroitin sulfate
      proteoglycans, and its degraded C-terminal G3 fragments in human plasma and
      observed that the versican G3 domain promoted blood coagulation. Silencing G3
      expression with small interfering RNA reduced the effect of G3 on coagulation.
      Plasma coagulation assays suggest that G3 enhances coagulation irrespective of
      its actions on platelets and white blood cells. To examine how versican affected
      blood coagulation, we used normal human plasma and different types of coagulation
      factor-deficient plasmas. The experiments indicated that versican enhanced
      coagulation through the extrinsic pathway, and that Factor VII was the target
      molecule. FVII activity assays showed that G3 activated FVII in the presence of
      plasma but not with purified FVII directly. Yeast two-hybrid,
      immunoprecipitation, and gel co-migration assays showed that G3 interacted with
      the tissue factor pathway inhibitor-1 (TFPI-1). TFPI-1 activity assays suggested
      that G3 inhibited TFPI-1 activity, allowing FVIIa and FXa to facilitate the
      coagulation process. G3-induced blood coagulation was further confirmed with a
      mouse model in a real-time manner. Taken together, these results indicate that
      versican may represent a new target for the development of therapies against
      atherosclerosis.

PMID- 16431925
TI  - Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A
      induced cell migration in epithelial cells.
AB  - Although spleen tyrosine kinase (Syk) is known to be important in hematopoietic
      cell development, the roles of Syk in epithelial cells have not been well
      studied. Limited data suggest that Syk plays alternate roles in carcinogenesis
      under different circumstances. In breast cancer, Syk has been suggested to be a
      tumor suppressor. In contrast, Syk is essential for murine mammary tumor virus
      mediated transformation. However, the roles of Syk in tumor migration are still
      largely unknown. Nasopharyngeal carcinoma, an unusually highly metastatic tumor,
      expresses Epstein-Barr virus LMP2A (latent membrane protein 2A) in most clinical
      specimens. Previously, we demonstrated LMP2A triggers epithelial cell migration.
      LMP2A contains an immunoreceptor tyrosine-based activation motif, which is
      important for Syk kinase activation in B cells. In this study, we explored
      whether Syk is important for LMP2A-mediated epithelial cell migration. We
      demonstrate that LMP2A expression can activate endogenous Syk activity. The
      activation requires the tyrosine residues in LMP2A ITAM but not YEEA motif, which
      is important for Syk activation by Lyn in B cells. LMP2A interacts with Syk as
      demonstrated by coimmunoprecipitation and confocal microscopy. Furthermore, LMP2A
      induced cell migration is inhibited by a Syk inhibitor and short interfering RNA.
      Tyrosines 74 and 85 in the LMP2A immunoreceptor tyrosine-based activation motif
      are essential for both Syk activation and LMP2A-mediated cell migration,
      indicating the involvement of Syk in LMP2A-triggered cell migration. The LMP2A
      Syk pathway may provide suitable drug targets for treatment of nasopharyngeal
      carcinoma.

PMID- 16431926
TI  - Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin
      dependent and -independent pathways.
AB  - Thiazolidinediones have been shown to up-regulate adiponectin expression in white
      adipose tissue and plasma adiponectin levels, and these up-regulations have been
      proposed to be a major mechanism of the thiazolidinedione-induced amelioration of
      insulin resistance linked to obesity. To test this hypothesis, we generated
      adiponectin knock-out (adipo-/-) ob/ob mice with a C57B/6 background. After 14
      days of 10 mg/kg pioglitazone, the insulin resistance and diabetes of ob/ob mice
      were significantly improved in association with significant up-regulation of
      serum adiponectin levels. Amelioration of insulin resistance in ob/ob mice was
      attributed to decreased glucose production and increased AMP-activated protein
      kinase in the liver but not to increased glucose uptake in skeletal muscle. In
      contrast, insulin resistance and diabetes were not improved in adipo-/-ob/ob
      mice. After 14 days of 30 mg/kg pioglitazone, insulin resistance and diabetes of
      ob/ob mice were again significantly ameliorated, which was attributed not only to
      decreased glucose production in the liver but also to increased glucose uptake in
      skeletal muscle. Interestingly, adipo-/-ob/ob mice also displayed significant
      amelioration of insulin resistance and diabetes, which was attributed to
      increased glucose uptake in skeletal muscle but not to decreased glucose
      production in the liver. The serum-free fatty acid and triglyceride levels as
      well as adipocyte sizes in ob/ob and adipo-/-ob/ob mice were unchanged after 10
      mg/kg pioglitazone but were significantly reduced to a similar degree after 30
      mg/kg pioglitazone. Moreover, the expressions of TNFalpha and resistin in adipose
      tissues of ob/ob and adipo-/-ob/ob mice were unchanged after 10 mg/kg
      pioglitazone but were decreased after 30 mg/kg pioglitazone. Thus, pioglitazone
      induced amelioration of insulin resistance and diabetes may occur adiponectin
      dependently in the liver and adiponectin independently in skeletal muscle.

PMID- 16431927
TI  - The catalytic activity of the eukaryotic initiation factor-2alpha kinase PKR is
      required to negatively regulate Stat1 and Stat3 via activation of the T-cell
      protein-tyrosine phosphatase.
AB  - Tyrosine phosphorylation of the transcription factors Stat1 and Stat3 is required
      for them to dimerize, translocate to the nucleus, and induce gene transcription.
      Nuclear Stat1 and Stat3 are dephosphorylated and deactivated by the T-cell
      protein-tyrosine phosphatase (TC-PTP), which facilitates the return of both
      proteins to the cytoplasm. The protein kinase PKR plays an important role in
      translational control through the modulation of eukaryotic initiation factor
      2alpha phosphorylation. Previous data have implicated PKR in cell signaling via
      regulation of Stat1 and Stat3, but the molecular mechanisms underlying these
      events have remained elusive. Using PKR(-/-) mouse embryonic fibroblasts and a
      conditionally active form of human PKR, we demonstrate herein that tyrosine (but
      not serine) phosphorylation of either Stat1 or Stat3 is impaired in cells with
      activated kinase. This reduction in Stat1 and Stat3 tyrosine phosphorylation by
      active PKR proceeds through TC-PTP, which is a substrate of the eukaryotic
      initiation factor-2alpha kinase both in vitro and in vivo. TC-PTP phosphorylation
      alone is insufficient to increase its in vivo phosphatase activity unless
      accompanied by the inhibition of protein synthesis as a result of PKR activation.
      These data reveal a novel function of PKR as a negative regulator of Stat1 and
      Stat3 with important implications in cell signaling.

PMID- 16431928
TI  - In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential
      localization within and around SC35 domains.
AB  - The bimolecular fluorescence complementation (BiFC) assay, which allows the
      investigation of interacting molecules in vivo, was applied to study complex
      formation between the splicing factor Y14 and nuclear export factor 1 (NXF1),
      which evidence indicates are functionally associated with nuclear mRNA. Y14
      linked to the COOH terminus of yellow fluorescent protein (YFP; YC-Y14), and NXF1
      fused to the NH2 terminus of YFP (YN-NXF1) expressed in MCF7 cells yielded BiFC
      upon specific binding. Fluorescence accumulated within and around nuclear
      speckles, suggesting the involvement of speckles in mRNA processing and export.
      Accordingly, BiFC depended on transcription and full-length NXF1.
      Coimmunoprecipitation of YC-Y14 with YN-NXF1, NXF1, Y14, and RNA indicated that
      YC-Y14 and YN-NXF1 functionally associate with RNA. Fluorescence recovery after
      photobleaching and fluorescence loss in photobleaching revealed that roughly half
      of the accumulated BiFC complexes were immobile in vivo. This immobile fraction
      was readily depleted by adenosine triphosphate (ATP) administration in
      permeabilized cells. These results suggest that a fraction of RNA, which remains
      in the nucleus for several hours despite its association with splicing and export
      proteins, accumulates in speckles because of an ATP-dependent mechanism.

PMID- 16431929
TI  - KIF14 and citron kinase act together to promote efficient cytokinesis.
AB  - Multiple mitotic kinesins and microtubule-associated proteins (MAPs) act in
      concert to direct cytokinesis (Glotzer, M. 2005. Science. 307:1735-1739). In
      anaphase cells, many of these proteins associate with an antiparallel array of
      microtubules termed the central spindle. The MAP and microtubule-bundling protein
      PRC1 (protein-regulating cytokinesis 1) is one of the key molecules required for
      the integrity of this structure (Jiang, W., G. Jimenez, N.J. Wells, T.J. Hope,
      G.M. Wahl, T. Hunter, and R. Fukunaga. 1998. Mol. Cell. 2:877-885; Mollinari, C.,
      J.P. Kleman, W. Jiang, G. Schoehn, T. Hunter, and R.L. Margolis. 2002. J. Cell
      Biol. 157:1175-1186). In this study, we identify an interaction between
      endogenous PRC1 and the previously uncharacterized kinesin KIF14 as well as other
      mitotic kinesins (MKlp1/CHO1, MKlp2, and KIF4) with known functions in
      cytokinesis (Hill, E., M. Clarke, and F.A. Barr. 2000. EMBO J. 19:5711-5719;
      Matuliene, J., and R. Kuriyama. 2002. Mol. Biol. Cell. 13:1832-1845; Kurasawa,
      Y., W.C. Earnshaw, Y. Mochizuki, N. Dohmae, and K. Todokoro. 2004. EMBO J.
      23:3237-3248). We find that KIF14 targets to the central spindle via its
      interaction with PRC1 and has an essential function in cytokinesis. In KIF14
      depleted cells, citron kinase but not other components of the central spindle and
      cleavage furrow fail to localize. Furthermore, the localization of KIF14 and
      citron kinase to the central spindle and midbody is codependent, and they form a
      complex depending on the activation state of citron kinase. Contrary to a
      previous study (Di Cunto, F., S. Imarisio, E. Hirsch, V. Broccoli, A. Bulfone, A.
      Migheli, C. Atzori, E. Turco, R. Triolo, G.P. Dotto, et al. 2000. Neuron. 28:115
      127), we find a general requirement for citron kinase in human cell division.
      Together, these findings identify a novel pathway required for efficient
      cytokinesis.

PMID- 16431930
TI  - Checkpoint control of mitotic exit--do budding yeast mind the GAP?
AB  - Cell cycle checkpoints can delay mitotic exit in budding yeast. The master
      controller is the small GTPase Tem1, with inputs from a proposed guanine
      nucleotide exchange factor (GEF), Lte1, and a GTPase-activating protein (GAP),
      Bub2/Bfa1. In this issue, Fraschini et al. (p. 335) show that GAP activity of
      Bub2/Bfa1 appears to be dispensable for inactivation of Tem1 in cells. Their
      results call into question the GTP/GDP switch model for Tem1 activity, as have
      other results in the past. The paper also focuses attention on the two spindle
      pole bodies as potential sites for regulation of Tem1.

PMID- 16431931
TI  - Lack of effect of metyrapone and exogenous cortisol on early porcine conceptus
      development.
AB  - A study was conducted to evaluate the influence of maternal cortisol on early
      conceptus development in pigs (Sus scrofa). The corticosteroid synthesis
      inhibitor metyrapone was injected daily during days 14-19 of pregnancy, without
      (n = 6) and with commensurate administration of cortisol (n = 6). Blood samples
      were taken via an indwelling jugular catheter on days 14 and 18, and conceptuses
      were harvested during surgery on day 20. Compared with vehicle-injected control
      dams (n = 7) plasma cortisol and aldosterone concentrations were decreased (P <
      0.01) by 52 and 29%, respectively, by metyrapone treatment. Cortisol
      administration reversed decreases in plasma cortisol by day 18. There were no
      treatment-associated effects on conceptus survival or size. Nor were there
      treatment-associated effects on allantoic fluid volume or content. Trophodermal
      glucocorticoid receptor (GR) mRNA expression decreased by 34% (P < 0.05) in
      metyrapone-treated pigs, and was not further influenced by concomitant
      administration of cortisol, thereby suggesting an influence of aldosterone on GR
      mRNA expression. Also, when all pigs were considered, there were treatment
      independent second-order polynomial regressions (P < 0.05) between maternal
      plasma cortisol concentrations and embryonic weight, allantoic size and allantoic
      glucose concentrations, and between plasma aldosterone concentrations and
      trophodermal GR mRNA expression. Such biphasic corticosteroid concentration
      versus tissue parameter curves are noteworthy, but difficult to interpret
      validly. They may suggest that an appropriate corticosteroid environment is
      necessary for optimal porcine embryonic development during this stage of
      gestation, but cannot overshadow the absence of treatment effects on the porcine
      embryonic measures evaluated.

PMID- 16431932
TI  - Influence of blood donation on O2 uptake on-kinetics, peak O2 uptake and time to
      exhaustion during severe-intensity cycle exercise in humans.
AB  - We hypothesized that the reduction of O2-carrying capacity caused by the
      withdrawal of approximately 450 ml blood would result in slower phase II O2
      uptake (VO2) kinetics, a lower VO2peak and a reduced time to exhaustion during
      severe-intensity cycle exercise. Eleven healthy subjects (mean +/- S.D. age 23 +/
      6 years, body mass 77.2 +/- 11.0 kg) completed 'step' exercise tests from
      unloaded cycling to a severe-intensity work rate (80% of the difference between
      the predetermined gas exchange threshold and the VO2peak) on two occasions
      before, and 24 h following, the voluntary donation of approximately 450 ml blood.
      Oxygen uptake was measured breath-by-breath, and VO2 kinetics estimated using non
      linear regression techniques. The blood withdrawal resulted in a significant
      reduction in haemoglobin concentration (pre: 15.4 +/- 0.9 versus post: 14.7 +/-
      1.3 g dl(-1); 95% confidence limits (CL): -0.04, -1.38) and haematocrit (pre: 44
      +/- 2 versus post: 41 +/- 3%; 95% CL: -1.3, -5.1). Compared to the control
      condition, blood withdrawal resulted in significant reductions in VO2peak (pre:
      3.79 +/- 0.64 versus post: 3.64 +/- 0.61 l min(-1); 95% CL: -0.04, - 0.27) and
      time to exhaustion (pre: 375 +/- 129 versus post: 321 +/- 99 s; 95% CL: -24, 
      85). However, the kinetic parameters of the fundamental VO2 response, including
      the phase II time constant (pre: 29 +/- 8 versus post: 30 +/- 6 s; 95% CL: 5, 
      3), were not altered by blood withdrawal. The magnitude of the VO2 slow component
      was significantly reduced following blood donation owing to the lower VO2peak
      attained. We conclude that a reduction in blood O2-carrying capacity, achieved
      through the withdrawal of approximately 450 ml blood, results in a significant
      reduction in VO2peak and exercise tolerance but has no effect on the fundamental
      phase of the VO2 on-kinetics during severe-intensity exercise.

PMID- 16431933
TI  - Novel application of flow propagation velocity and ischaemia-modified albumin in
      analysis of postexercise cardiac function in man.
AB  - The present study employed novel echocardiographic tools and cardiac markers to
      obtain a greater understanding of the aetiology and time course of altered
      cardiac function and cardiac damage following prolonged exercise and, in
      particular, the possible role of transient ischaemia within these phenomena.
      Fourteen runners in the 2004 London Marathon were assessed pre-, immediately post
      , 1 h post- and 24 h postcompletion of the race. Left ventricular function was
      examined echocardiographically using 2-D, M-mode, tissue Doppler imaging and flow
      propagation velocity (Vp). Venous blood samples were analysed for N-terminal pro
      B-type natriuretic peptide (proBNP), cardiac troponin T (cTnT) and ischaemia
      modified albumin (IMA). Left ventricular (LV) diastolic filling was altered on
      completion of the race, as indicated by significant decreases in mean early to
      late diastolic myocardial wave (E':A') ratio and Vp (from 1.82 +/- 0.9 to 1.32 +/
      0.32, and from 67.5 +/- 9.3 to 60.2 +/- 8.2 cm s(-1), respectively, P < 0.05),
      accompanied by an increase in proBNP (from 21.6 +/- 11 to 47.08 +/- 19.5 pg l(
      1), P < 0.05). The observed reduction in LV diastolic filling following
      completion of a marathon, unrelated to changes in heart rate or loading
      parameters, indicates an intrinsically mediated change in diastolic filling.
      Exercise-induced elevations in cTnT in nine individuals (range, 0.023-0.37 microg
      l(-1)) were indicative of minor cardiac damage. A significant reduction in IMA
      was observed after the marathon (from 63.68 +/- 9.83 to 44.94 +/- 16.13 Um l(-1),
      P < 0.05), unrelated to the alterations in cardiac function, proBNP or cTnT. The
      absence of an elevation in IMA suggests that exercise-induced myocardial
      ischaemia did not occur and therefore could not explain the changes in cardiac
      function or biomarkers. Future studies in this area should investigate
      alternative diagnostic tools for the detection of transient ischaemia, and other
      potential mechanisms, in order to extend the understanding of this phenomenon.

PMID- 16431935
TI  - Cardiac electrophysiology and tissue structure: bridging the scale gap with a
      joint measurement and modelling paradigm.
AB  - Significant tissue structures exist in cardiac ventricular tissue that are of
      supracellular dimension. It is hypothesized that these tissue structures
      contribute to the discontinuous spread of electrical activation, may contribute
      to arrhymogenesis and also provide a substrate for effective cardioversion.
      However, the influences of these mesoscale tissue structures in intact
      ventricular tissue are difficult to understand solely on the basis of
      experimental measurement. Current measurement technology is able to record at
      both the macroscale tissue level and the microscale cellular or subcellular
      level, but to date it has not been possible to obtain large volume, direct
      measurements at the mesoscales. To bridge this scale gap in experimental
      measurements, we use tissue-specific structure and mathematical modelling. Our
      models have enabled us to consider key hypotheses regarding discontinuous
      activation. We also consider the future developments of our intact tissue
      experimental programme.

PMID- 16431934
TI  - Intestinal phosphate absorption and the effect of vitamin D: a comparison of rats
      with mice.
AB  - Previously, it was thought that intestinal phosphate transport occurred
      exclusively in the proximal small intestine of rodents and humans. However, a
      recent study has demonstrated that the ileum of mice contributes significantly to
      the absorption of dietary phosphate, but it is not known whether this region is
      also an important site of phosphate absorption in the rat. In the present study,
      we have investigated the mRNA and protein levels of the sodium-phosphate
      cotransporter, NaPi-IIb, in three regions of rat and mouse small intestine, and
      related its expression levels to the rate of net phosphate absorption, as
      measured using the in situ intestinal loop technique. 1,25-Dihydroxyvitamin D3 is
      an important physiological regulator of intestinal phosphate absorption that
      increases phosphate transport in both the duodenum and jejunum of the rat. Based
      on the recently proposed regional profile of phosphate absorption along the mouse
      small intestine, we have re-evaluated the effects of 1,25-dihydroxyvitamin D3
      using three distinct regions of the mouse and rat small intestine. Our studies
      have revealed important differences in the intestinal handling of phosphate
      between mice and rats. In mice, maximal phosphate absorption occurs in the ileum,
      which is paralleled by the highest expression levels of NaPi-IIb mRNA and
      protein. In contrast, in rats maximal absorption occurs in the duodenum with very
      little absorption occurring in the ileum, which is similar to the pattern
      reported in humans. However, in both rodent species only the jejunum shows an
      increase in phosphate absorption in response to treatment with 1,25
      dihydroxyvitamin D3.

PMID- 16431936
TI  - Tolerance to low O2: lessons from invertebrate genetic models.
AB  - There have been extensive studies and experiments on cells, tissues and animals
      that are susceptible to low O2, and many pathways have been discovered that can
      lead to injury in mammalian tissues. But other pathways that can help in the
      survival of low O2 have also been discovered in these same tissues. It should be
      noted, however, that the mechanisms that can lead to better survival in
      susceptible mammalian tissues have quantitatively a 'narrow range' for recovery,
      since these tissues are inherently at risk. Another strategy for understanding
      the susceptibility of organisms is to learn about pathways used by anoxia
      resistant animals. Approximately a decade ago, I and my co-workers discovered
      that one such animal, Drosophila melanogaster, is very tolerant of low O2. Here,
      I detail some of the studies that we performed and the strategies that we
      developed to understand the mechanisms that underlie the fascinating resistance
      of Drosophila to measured partial pressure of O2 of zero. We employed three ideas
      to try to address our questions: (1) mutagenesis screens to identify loss-of
      function mutants; (2) microarrays on adapted versus naive flies; and (3) studying
      cell biology and physiology of genes that seem important in flies and mammals.
      The hope is to learn from these studies about the fundamental basis of tolerance
      to the lack of O2, and with this knowledge be able to develop better therapies
      for the future.

PMID- 16431938
TI  - Ocular versus extraocular neovascularization: mirror images or vague
      resemblances.

PMID- 16431940
TI  - Changes in the optic disc excavation of children affected by cerebral visual
      impairment: a tomographic analysis.
AB  - PURPOSE: To obtain quantitative data on the optic disc excavation in children
      affected by cerebral visual impairment (CVI) by using the Heidelberg Retinal
      Tomograph (HRT)-II (Heidelberg Engineering, Heidelberg, Germany). METHODS: A
      total of 24 subjects affected by CVI (mean age, 7.28 years) were examined: 16 in
      alert conditions and 8 under general anesthesia. The following parameters of the
      optic nerve head were examined: disc area, cup area, rim area, cup volume, rim
      volume, cup-to-disc area ratio, mean cup depth, maximum cup depth, cup shape
      measure, and mean retinal nerve fiber layer (RNFL) thickness. The tomographic
      results in children with CVI were compared with those of 88 normal, alert
      subjects of similar age. RESULTS: The optic disc of patients with CVI appeared
      smaller than normal. Its excavation, however, was more pronounced. Several
      tomographic parameters were altered in CVI-affected subjects. Statistical
      analysis showed a highly significant probability in cup-to-disc area ratio (P <
      0.01, both eyes), rim area (P < 0.01, both eyes), cup shape measure (P < 0.01,
      right eye; P < 0.01, left eye), and mean RNFL thickness (P < 0.01, right eye; P <
      0.01, left eye). A novel observation was temporal atrophy of the optic nerve head
      in CVI. CONCLUSIONS: The data provide a tridimensional, objective evaluation of
      the anatomic alterations of the optic nerve head in children with CVI.
      Furthermore, tomographic standards for optic disc shape in normal children are
      set for the first time.

PMID- 16431939
TI  - The novel A4435G mutation in the mitochondrial tRNAMet may modulate the
      phenotypic expression of the LHON-associated ND4 G11778A mutation.
AB  - PURPOSE: To investigating the role of mitochondrial haplotypes in the development
      of Leber's hereditary optic neuropathy (LHON) associated with the ND4 G11778A
      mutation in Chinese families. METHODS: A three-generation Chinese family with
      LHON was studied by clinical and genetic evaluation as well as molecular and
      biochemical analysis of mitochondrial (mt)DNA. RESULTS: This family exhibits a
      high penetrance and expressivity of visual impairment. The average age at onset
      was 13.9 years in this family. Of the family members, 86% of the male and 29% of
      the female matrilineal relatives had visual loss, with a wide range of severity,
      from blindness to nearly normal vision. Molecular analysis of mtDNA identified
      the homoplasmic ND4 G11778A mutation and 35 other variants, belonging to the
      Asian haplogroup D5. Of other variants, the novel homoplasmic A4435G mutation
      absent in 164 Chinese controls is localized at 3' end adjacent to the anticodon,
      at conventional position 37 (A37), of tRNAMet. The adenine (A37) at this position
      of tRNAMet is extraordinarily conserved from bacteria to human mitochondria. This
      modified A37 was shown to contribute to the high fidelity of codon recognition
      and to the structural formation and stabilization of functional tRNAs. In fact,
      the significant reduction of the steady state levels in tRNAMet was observed in
      cells carrying the both the A4435G and G11778A mutations but not cells carrying
      only the G11778A mutation. Thus, a failure in mitochondrial tRNA metabolism,
      caused by the A4435G mutation, may worsen the mitochondrial dysfunction
      associated with the primary G11778A mutation. CONCLUSIONS: The novel tRNAMet
      A4435G mutation has a potential modifier role in increasing the penetrance and
      expressivity of the primary LHON-associated G11778A mutation in this Chinese
      family.

PMID- 16431941
TI  - Longitudinal changes in visual acuity in keratoconus.
AB  - PURPOSE: The present investigation aimed to identify factors that predict reduced
      visual acuity in keratoconus from a prospective, longitudinal study. METHODS:
      This report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK)
      Study used 7 years of follow-up data from 953 CLEK subjects who did not have
      penetrating keratoplasty in either eye at baseline and who provided enough data
      to compute the slope of the change over time in high- or low-contrast best
      corrected visual acuity (BCVA). Outcome measures included these slopes and
      whether the number of letters correctly read decreased by 10 letters or more in
      at least one eye in 7 years. RESULTS: Mean age of the subjects at the first
      follow-up visit was 40.2 +/- 11.0 years (mean +/- SD). Overall, 44.4% were
      female, and 71.9% were white. The slope of the change in high- and low-contrast
      BCVA (-0.29 +/- 1.5 and -0.58 +/- 1.7 letters correct/year, respectively)
      translated into expected 7-year decreases of 2.03 high- and 4.06 low-contrast
      letters correct. High- and low-contrast visual acuity decreases of 10 or more
      letters correct occurred in 19.0% and 30.8% of subjects, respectively.
      Independent predictors of reduced high- and low-contrast BCVA included better
      baseline acuity, steeper first definite apical clearance lens (FDACL), and fundus
      abnormalities. Each diopter of steeper baseline FDACL predicted an increased
      deterioration of 0.49 high- and 0.63 low-contrast letters correct. CONCLUSIONS:
      CLEK Study subjects with keratoconus exhibited a slow but clear decrease in BCVA
      during follow-up, with low-contrast acuity deteriorating more rapidly than high
      contrast. Better baseline BCVA, steeper FDACL, and fundus abnormalities were
      predictive of greater acuity loss with time.

PMID- 16431942
TI  - Prevalence and treatment of Helicobacter pylori in patients with blepharitis.
AB  - PURPOSE: Helicobacter pylori is a major pathogen etiologically associated with
      gastritis, peptic ulcer disease, gastric cancer, and primary gastric lymphoma.
      This study was conducted to investigate a possible association between
      Helicobacter pylori infection and blepharitis. Two hundred fifty consecutive
      patients with symptomatic blepharitis and 250 control subjects without
      blepharitis symptoms were evaluated. After exclusions, the blepharitis group
      consisted of 186 patients with blepharitis and a control group of 215 patients.
      METHODS: Blepharitis was diagnosed on the basis of findings in ophthalmic and
      dermatologic examinations. All patients underwent a 13C-urea breath test (UBT) to
      detect H. pylori infection, and impression cytology was performed before and
      after eradication therapy. The follow-up period was 4 months +/- 28 days.
      RESULTS: The blepharitis group showed an H. pylori infection prevalence of
      approximately 76.3% (UBT-positive group with blepharitis: n = 142 patients),
      compared with 42.3% of the control group (UBT-positive group with blepharitis
      [although asymptomatic]: n = 66 patients; UBT-positive group without blepharitis:
      n = 25 patients). Furthermore, we observed blepharitis in 30.6% (n = 66 patients)
      of UBT-positive control subjects and 13.4% (n = 29 patients) of UBT-negative
      control subjects. Impression cytology revealed that blepharitis was more severe
      in UBT-positive patients than in negative ones, and a clinical improvement in
      blepharitis was noted in approximately 50% of patients after H. pylori
      eradication. CONCLUSIONS: Even though possible sources of error in defining the
      association of two highly prevalent conditions must be considered, the data seem
      to validate an association between H. pylori infection and blepharitis, but may
      not be indicative of a causal association. Eradication of H. pylori improved
      ocular cytology results. It is possible that chronic blepharitis is an
      extradigestive manifestation of H. pylori infection.

PMID- 16431943
TI  - Evaluation of computer-based volume measurement and porous polyethylene channel
      implants in reconstruction of large orbital wall fractures.
AB  - PURPOSE: To describe the use of computer-based orbital volume measurement as a
      predictor of late enophthalmos, and to assess the effectiveness of the MedPor
      (Porex Surgical Products Group, Newnan, GA) porous polyethylene channel implant
      to restore orbital volume in repairing large orbital wall fractures. METHODS:
      Sixteen patients with unilateral large orbital fractures were included. Computed
      tomographic (CT) scans were used to obtain computer-based orbital volume
      measurement to predict the likelihood of late enophthalmos and to assess the
      change in orbital volume before and after surgery. The effectiveness of a channel
      implant was evaluated by the orbital volume and postoperative exophthalmetric
      measurement. RESULTS: The average time interval between injury and surgery was
      17.4 +/- 10 days, and the mean follow-up was 9 months. The orbital volume of the
      injured orbit was significantly increased (mean, 4.22 +/- 2.61 cm2) compared with
      the unaffected orbit before surgery (t = 3.046, P = 0.005). There was not a
      significant difference in orbital volume between the two orbits after orbital
      reconstruction (t = 0.069, P = 0.945). The orbital volume change after
      reconstructive surgery was significantly positively correlated with the decrease
      of enophthalmos (r = 0.715, P = 0.001; enophthalmos [E] = 0.72; volume increment
      [V] = 0.06). To resolve 2 mm enophthalmos, more than 2.9 cm3 orbital volume
      augmentation is recommended for early reconstructive surgery. Postoperative CT
      scan showed most of the channel implants to be well positioned. CONCLUSIONS:
      Computer-based orbital volume measurement from a CT scan is useful in the
      posttraumatic evaluation of orbital fractures, and it can help predict the degree
      of late enophthalmos that can be expected. Orbital reconstruction with the MedPor
      channel implant (Porex Surgical Products Group), when indicated, is recommended,
      especially for large orbital wall fractures.

PMID- 16431944
TI  - Measures of visual function and their association with driving modification in
      older adults.
AB  - PURPOSE: Older drivers may place restrictions on their driving by reducing their
      mileage and avoiding high-risk driving situations in an effort to improve safety.
      This project identifies what types of visual function loss are associated with
      subsequent driving modifications. METHODS: Data were used from the baseline and 2
      year follow-up rounds of the Salisbury Eye Evaluation project, a cohort study of
      2520 older adults. Measures of visual function tested were visual acuity,
      contrast sensitivity, visual fields, and glare sensitivity. Driving information
      was self-reported. Among drivers at baseline who continued to drive at follow-up,
      multiple logistic regression was used to estimate the odds of incident driving
      modification by visual function status. RESULTS: Worse baseline scores in acuity,
      contrast sensitivity, and central and lower peripheral visual fields were
      individually associated with an increased odds of reduced mileage 2 years later
      (linear trend P < 0.05). Worse baseline scores in contrast sensitivity and
      central and lower peripheral visual fields were individually associated with a
      greater odds of cessation of night driving 2 years later, whereas worse baseline
      acuity scores were associated with an increased odds of cessation of driving in
      an unfamiliar areas 2 years later (linear trend P < 0.05). CONCLUSIONS: Older
      drivers with worse visual function were more likely to modify their driving by
      reducing mileage and avoiding high-risk driving situations. Furthermore, these
      modifications to driving differed depending on what type of visual function was
      affected.

PMID- 16431945
TI  - Trends in eye injury in the United States, 1992-2001.
AB  - PURPOSE: To report the trends of eye injury in the United States from 1992
      through 2001. METHODS: The National Ambulatory Medical Care Survey, National
      Hospital Ambulatory Medical Care Survey, and the National Hospital Discharge
      Survey were used to collect information on eye injuries from 1992 to 2001. Rates
      of eye injury per 1000 population were calculated according to age, gender, and
      race. RESULTS: From 1992 through 2001, the overall estimated rate of eye injury
      ranged from 8.2 to 13.0 per 1000 population. During this period the incidence of
      eye injury significantly declined overall, in persons aged 39 years and younger,
      in both genders, and in the black and white populations (all P <0.05).
      CONCLUSIONS: From 1992 through 2002, the incidence of eye injury in the United
      States declined overall, in persons aged 39 and younger, in both genders, and in
      both racial groups. Certain segments of the population, however, continued to be
      at high risk (i.e., males and persons aged 39 and younger) of eye injury and
      represent those groups toward whom prevention resources should be directed.

PMID- 16431946
TI  - Development of a questionnaire to assess vision problems under low luminance in
      age-related maculopathy.
AB  - PURPOSE: To develop a questionnaire for assessing self-reported visual problems
      under low luminance and at night for use in studies on age-related maculopathy
      (ARM). METHODS: The questionnaire was developed in three steps: (1) Content for
      questionnaire items was identified through focus groups of older adults with ARM
      and those exhibiting normal retinal aging. The topic for discussion was "vision
      at night and under low lighting." Discussion was audiotaped, transcribed, and
      subjected to content analysis to identify problem categories expressed by
      patients. (2) This content was used to develop a preliminary questionnaire
      administered by telephone to persons with ARM or normal retinal aging. Principal
      components analysis identified groups of items that formed the questionnaire's
      subscales that were evaluated for internal consistency, and an item-reduction
      strategy was implemented to generate a briefer questionnaire. (3) Psychometric
      properties of the shortened Low-Luminance Questionnaire (LLQ) were determined,
      including construct validity, criterion validity, and test-retest reliability.
      RESULTS: The 32-item LLQ has six subscales (driving, extreme lighting, mobility,
      emotional distress, general dim lighting, and peripheral vision), all with good
      internal consistency (Cronbach alpha > or = 0.82). Scores on LLQ subscales
      correlated moderately with nearly all National Eye Institute Visual Function
      Questionnaire (NEI VFQ)-25 subscales and decreased in value (indicating more
      disability) for patients with increasing ARM disease severity. Whereas rod
      mediated parameters of dark adaptation were significantly associated with LLQ
      subscale scores (r = 0.19-0.43, all P < 0.03), cone-mediated parameters were not.
      Test-retest reliability ranged from 0.74 to 0.88 for all subscales (P < 0.0001),
      except for peripheral vision (0.46; P = 0.0003), which also exhibited a ceiling
      effect in almost half of the respondents. CONCLUSIONS: The 32-item LLQ, derived
      from the content of focus group comments by persons with ARM, has good construct
      validity, subscale scores related to rod-mediated visual function, and good test
      retest reliability for five of six subscales. The LLQ may ultimately be useful in
      patient-centered evaluation of the outcome of interventions to prevent ARM or to
      arrest progression of early disease.

PMID- 16431947
TI  - Complement factor H variant Y402H is a major risk determinant for geographic
      atrophy and choroidal neovascularization in smokers and nonsmokers.
AB  - PURPOSE: The complement factor H (CFH) gene polymorphism Y402H (1277T-->C) has
      been associated with susceptibility to age-related macular degeneration (AMD).
      The purpose of this study was to confirm this association in a U.K. population,
      to determine whether the association holds for both geographic atrophy (GA) and
      choroidal neovascularization (CNV), and to investigate interactions with smoking.
      METHODS: A case-control study was undertaken in 443 cases of AMD, with 262
      spouses as control subjects. All subjects completed a health and lifestyle
      questionnaire, had an ophthalmic assessment with fundus photography, and were
      genotyped. RESULTS: The frequencies of the C allele and CC genotype were
      significantly higher in cases than in controls. In comparison to the TT genotype,
      the odds ratios for AMD associated with the CT and CC genotypes were 3.1 (CI 2.0
      4.6) and 6.3 (CI 3.8-10.4), respectively. The results were similar in subgroup
      analyses confined to cases with GA or CNV. The findings were also similar for
      subgroup analyses restricted to subjects who had never smoked, moderate smokers,
      or heavier smokers (>20 pack years of smoking). Heavier smokers with the CC
      genotype may be particularly at risk. The frequency of the CC genotype did not
      differ significantly between cases with and without a family history of AMD.
      There was no evidence that genotype had any influence on age at onset of disease.
      CONCLUSIONS: The CFH Y402H variant is strongly associated with both GA and CNV in
      the U.K. population. This association is similar in smokers and nonsmokers.
      Heavier smokers with the CC genotype may be at particular risk.

PMID- 16431948
TI  - Conjunctival surface changes in patients with Sjogren's syndrome: a transmission
      electron microscopy study.
AB  - PURPOSE: To demonstrate the ultrastructural appearance of the conjunctival
      surface epithelium in patients with Sjogren's syndrome (SS) compared with normal
      subjects. METHODS: Conjunctival tissue specimens from seven normal subjects and
      eight patients with SS were obtained by bulbar conjunctival biopsy and examined
      by transmission electron microscopy. RESULTS: The average number of microvilli
      per 8.3 microm epithelial length was significantly lower in the SS group than
      that in the control group (19.6 +/- 2.5 vs. 28.0 +/- 3.4, P < 0.0001). The
      microvillus height (0.539 +/- 0.151 microm) and height-width ratio (1.825 +/-
      0.549) in the conjunctival epithelium in the SS group were significantly lower
      than those (height: 0.946 +/- 0.117 microm, P < 0.001; and height-width ratio:
      3.717 +/- 0.696, P < 0.0001) in normal individuals. The microvilli in the SS
      group were wider than those in the control group (P = 0.003). Furthermore, the
      average number of secretory vesicles (per 8.3 microm epithelial length) in the
      apical conjunctival epithelial cell was significantly reduced in the SS group
      (16.4 +/- 6.8 vesicles), compared with the control group (34.7 +/- 1.2 vesicles,
      P = 0.003). In addition, although the ocular surface glycocalyx (OSG) was always
      present in control subjects, it was not detectable in all but one of the SS
      conjunctival specimens. CONCLUSIONS: The ultrastructural morphology of the apical
      conjunctival epithelium is altered in patients with SS. The findings suggest that
      an intact OSG may play a key role in the maintenance of a healthy ocular surface,
      possibly by preventing abrasive influences on the apical epithelial cells.

PMID- 16431949
TI  - Expression of keratin 12 and maturation of corneal epithelium during development
      and postnatal growth.
AB  - PURPOSE: To determine the kinetics of corneal epithelial maturation during
      embryonic development and postnatal growth. METHODS: Expression patterns of
      keratin (K)12 and K14 were determined in mouse embryos (embryonic days [E]15.5
      19.5), corneas of postnatal day (P)0 to 10 months, and healing corneas after
      epithelial debridement in P30 and P90 mice. The expression of alkaline
      phosphatase (AP) was determined during postnatal growth and healing of epithelial
      debridement of Krt12(Cre/Cre)/ZAP bitransgenic mice. RESULTS: During embryonic
      development, K12 expression by corneal peridermal epithelium commenced at E15.5.
      In the period from E15.5 to P10, the expression of K12 was restricted to the
      suprabasal and/or superficial cells of the corneal epithelium, whereas the K14
      expression was restricted to the basal cells. After P30, K12 expression was
      sporadically detected in the basal corneal epithelium, and the number of K12
      positive basal cells increased as the mice grew older. The number of K14-positive
      cells that coexpressed K12 increased with age and reached a plateau after P180.
      Healing of the debrided epithelium facilitated the increase in K14-positive cells
      that coexpressed K12. Many basal cells of Krt12(Cre/Cre)/ZAP mice remained
      undifferentiated and expressed LacZ at P15, and they then differentiated to
      express Cre, which leads to excision of LacZ and AP expression. CONCLUSIONS: In
      the mouse, the corneal epithelium does not become fully mature until 3 to 6
      months after birth, in that a significant number of corneal basal epithelial
      cells of young mice (<P30), which derive from embryonic surface ectoderm remain
      undifferentiated and serve as corneal epithelial progenitor cells. These
      progenitor cells may have some stem cell characteristics.

PMID- 16431950
TI  - Transplantation of tissue-engineered epithelial cell sheets after excimer laser
      photoablation reduces postoperative corneal haze.
AB  - PURPOSE: To apply tissue-engineered cell sheet transplantation after excimer
      laser keratectomy as a novel approach for the reduction of postoperative corneal
      haze. METHODS: Limbal biopsy specimens were obtained, and epithelial cells were
      cultured on temperature-responsive culture inserts without the use of feeder
      cells. Laser keratectomy (7.0-mm ablation zone and 160-microm depth) was
      performed in the contralateral eye, and autologous epithelial cell sheets were
      transplanted to the ablated corneal stroma. Transplant and control group eyes
      were assessed by slit lamp biomicroscopy, and corneal haze was scored in a masked
      fashion, according to the Fantes grading scale. For further examination
      histologic and immunohistochemical analyses were performed. RESULTS: Tissue
      engineered cell sheets produced stable attachment to the laser-ablated sites,
      resulting in epithelialization, 5 minutes after transplantation. Conversely,
      control corneas required 3 to 5 days for complete re-epithelialization. At both 1
      and 2 months after surgery, corneal haze was significantly inhibited in the
      transplant group. Histologic analyses showed that the number of keratocytes
      undergoing apoptosis was decreased in the transplant group at 3 days after
      surgery. Similarly, the expression of both collagen III and alpha-smooth muscle
      actin, which may enhance corneal haze, were diminished in the transplant group at
      2 months. CONCLUSIONS: The transplantation of tissue-engineered epithelial cell
      sheets can successfully prevent the development of corneal haze after excimer
      laser keratectomy.

PMID- 16431951
TI  - Gene transfer to corneal epithelium and keratocytes mediated by ultrasound with
      microbubbles.
AB  - PURPOSE: The cornea is an ideal organ for evaluating gene transfer because it can
      be treated noninvasively and monitored easily. The present study was performed to
      investigate the practical efficacy and safety of ultrasound (US) plus microbubble
      (MB)-mediated gene transfer to cornea. METHODS: Cultured rabbit corneal
      epithelial (RC-1) cells were incubated in 24-well dishes with plasmid DNA having
      a green fluorescent protein (GFP) gene under a cytomegalovirus promoter. The
      cells were exposed to US under different intensities (1 MHz; power, 0.5
      approximately 2 W/cm2; duration, 15-120 seconds; duty cycle, 20%-100%). The
      effect of simultaneous stimulation with MBs was also examined. Gene transfer was
      quantified by counting the number of GFP-positive cells under microscopy.
      Furthermore, in vivo gene transfer was examined by GFP plasmid injection into
      rabbit cornea and US exposure with MBs. RESULTS: In the in vitro study, DNA
      exposure alone could not transfer gene into cultured RC-1 cells; US enhanced gene
      transfer slightly. Coexposure with MBs significantly increased gene transfer
      efficiency. In the in vivo study, DNA injection alone could transfer the gene to
      a limited degree, but plasmid injection plus US with MBs strongly increased gene
      transfer efficiency without apparent tissue damage, and gene transfer was
      achieved two dimensionally. CONCLUSIONS: US with MBs greatly increases gene
      transfer to in vivo and in vitro corneal cells. This noninvasive gene transfer
      method may be a useful tool for clinical gene therapy.

PMID- 16431952
TI  - Structural abnormalities of the cornea and lid resulting from collagen V
      mutations.
AB  - PURPOSE: Type V collagen forms heterotypic fibrils with type I collagen and
      accounts for 10% to 20% of corneal collagen. The purpose of this study was to
      define the ocular phenotype resulting from mutations in the type V collagen genes
      COL5A1 and COL5A2 and to study the pathogenesis of anomalies in a Col5a1
      deficient mouse. METHODS: Seven patients with classic Ehlers-Danlos syndrome
      (EDS) due to COL5A1 haploinsufficiency and one with an exon-skipping mutation in
      COL5A2 underwent an ocular examination, corneal topography, pachymetry, and
      specular microscopy. A Col5a1-haploinsufficient mouse model of classic EDS was
      used for biochemical and immunochemical analyses of corneas. Light and electron
      microscopy were used to quantify stromal thickness, fibril density, fibril
      structure, and diameter. RESULTS: Five males and three females (mean age, 26 +/-
      13.57 years; range, 11-52) were studied. All patients had "floppy eyelids." The
      corneas of all eyes were thinner (mean corneal thickness: 435.75 +/- 12.51
      microm) when compared with control corneas (568.89 +/- 28.46 microm; P < 0.0001).
      In the Col5a1+/- mouse cornea, type V collagen content was reduced by
      approximately 49%, and stromal thickness was reduced by approximately 26%. Total
      collagen deposition in Col5a1(+/-) corneas also was reduced. Collagen fibril
      diameters were increased, but fibril density was decreased throughout the stroma
      at all developmental stages. CONCLUSIONS: In the eye, COL5A1 and COL5A2 mutations
      manifest as abnormally thin and steep corneas with floppy eyelids. Mechanisms
      involved in producing the latter anomalies probably involve altered regulation of
      collagen fibrillogenesis due to abnormalities in heterotypic type I/V collagen
      interactions similar to those observed in the Col5a1+/- mouse cornea.

PMID- 16431953
TI  - Two-year preclinical testing of perfluoropolyether polymer as a corneal inlay.
AB  - PURPOSE: To assess the long-term biocompatibility and optical clarity of a
      perfluoropolyether (PFPE) polymer as a corneal inlay. METHODS: A 4-mm-diameter
      PFPE inlay was implanted under a microkeratome flap in the corneas of rabbits (n
      = 16) and maintained for predetermined time points of 6, 12, or 24 months. These
      were compared with normal (n = 3) and time-matched sham-wounded rabbit corneas (n
      = 8). All corneas were monitored clinically with a slit lamp. Histology was
      performed on all eyes on termination to assess the tissue response. RESULTS: Some
      sham and implanted animals were discontinued from study 1 to 2 days after surgery
      because of flap dislodgement. Ten animals with PFPE inlays remained in the study,
      and 7 of these were maintained to their predetermined time point for up to 2
      years (3 were discontinued because of peripheral corneal defects). The corneas of
      these 7 animals remained clear and healthy, tear film remained normal, and there
      were no signs of inflammation, neovascularization, or increased conjunctival
      redness. All inlays remained centered and optically clear (clarity 85% or
      greater). Histology showed PFPE was biostable. The epithelia of operated corneas
      were stratified but slightly thinned compared with those of normal corneas.
      Stromal tissue anterior and posterior to each inlay appeared normal. Keratocytes
      in the vicinity of the inlay were normal in distribution but showed increased
      vacuolation, indicating tissue repair after the surgery. CONCLUSIONS: The PFPE
      polymer maintained a high level of optical clarity and showed long-term
      biocompatibility for up to 2 years when implanted as an inlay in the rabbit
      cornea.

PMID- 16431954
TI  - Kruppel-like factor 6 (KLF6) affects the promoter activity of the alpha1
      proteinase inhibitor gene.
AB  - PURPOSE: Keratoconus is a progressive disease that thins and scars the cornea. In
      keratoconus corneas, levels of degradative enzymes, including lysosomal acid
      phosphatase (LAP) and cathepsin B, are elevated, and those of inhibitors alpha1
      proteinase inhibitor (alpha1-PI) and alpha2-macroglobulin (alpha2-M) are reduced.
      The present study explored the possible involvement in keratoconus of Kruppel
      like factor 6 (KLF6), a transcription factor previously described to be essential
      for the integrity of the corneal epithelium. The transcript and proteins level of
      KLF6 and its action in regulating the genes affected in keratoconus were examined
      in this study. METHODS: Semiquantitative RT-PCR, Western blot analysis,
      immunofluorescence and in situ hybridization were used to investigate the
      expression of KLF6 mRNA and protein in normal and keratoconus corneas. Modulation
      by KLF6 of the promoter activity of alpha1-PI, LAP, cathepsin B, and alpha2-M
      genes was studied after transient transfection of KLF6 expression plasmid into
      corneal epithelial cells using promoter-reporter gene assays. Chromatin
      immunoprecipitation (ChIP) assays were performed to confirm the interactions
      between KLF6 and promoters of the genes affected in keratoconus. RESULTS: A
      global increased expression of the transcription factor KLF6 in terms of mRNAs
      and proteins was observed in total cornea and/or the epithelium in a substantial
      number of the keratoconus specimens. The promoter activity of the human alpha1-PI
      gene was suppressed by expression of KLF6 in corneal epithelial cells. The ChIP
      assay confirmed a physical interaction between KLF6 and the alpha1-PI promoter.
      CONCLUSIONS: Transcription factor KLF6 downregulates the alpha1-PI gene in
      corneal epithelial cells and may thereby be involved in keratoconus.

PMID- 16431955
TI  - Involvement of insulin-like growth factor-I and insulin-like growth factor
      binding protein-3 in corneal fibroblasts during corneal wound healing.
AB  - PURPOSE: The involvement of downstream messengers of transforming growth factor
      (TGF)-beta in the differentiation of corneal fibroblasts into myofibroblasts was
      investigated. The effects of insulin-like growth factor (IGF)-I and insulin-like
      growth factor binding protein (IGFBP)-3 upregulated by TGF-beta were examined in
      human corneal fibroblasts, and the possible involvement of IGF axis components in
      corneal wound healing was assessed in a mouse model. METHODS: Human corneal
      fibroblasts were incubated with TGF-beta2 or IGF-I, to investigate IGF-I, IGF-II,
      IGFBP-3, type I collagen, and alpha-smooth muscle actin (alpha-SMA) mRNA, as well
      as IGFBP-3 protein expression, during myofibroblast differentiation. DNA
      synthesis was evaluated with a 5-bromo-2'-deoxyuridine (BrdU) incorporation
      assay. IGFBP-3 mRNA expression, protein expression, and immunolocalization were
      investigated in mouse corneas after photorefractive keratectomy (PRK). RESULTS:
      TGF-beta2 treatment induced expression of IGF-I and IGFBP-3 mRNA and of IGFBP-3
      protein in human corneal fibroblasts. TGF-beta2 and IGF-I both stimulated
      expression of type I collagen. TGF-beta2 but not IGF-I potently stimulated alpha
      SMA mRNA expression. IGF-I potently stimulated basal DNA synthesis, whereas IGFBP
      3 inhibited it. IGF-I potently stimulated proliferation of TGF-beta2-activated
      myofibroblasts without reversing the activated fibrogenic phenotype, whereas
      IGFBP-3 suppressed IGF-I-induced proliferation of corneal fibroblasts. IGFBP-3
      mRNA and protein increased in mouse corneas soon after PRK, when in vivo
      immunostaining of the corneas showed expression of IGFBP-3 in the deep layer of
      the corneal stroma. CONCLUSIONS: These results suggest that during corneal wound
      healing, TGF-beta stimulates IGF axis components, whereas IGFBP-3 may modulate
      IGF-I-induced myofibroblast proliferation to suppress corneal mesenchymal
      overgrowth.

PMID- 16431956
TI  - A femtosecond laser creates a stronger flap than a mechanical microkeratome.
AB  - PURPOSE: To compare corneal flaps made with a femtosecond (FS) laser with those
      made with a mechanical microkeratome (MM) in rabbits, measuring early
      postoperative inflammation and apoptosis and late postoperative adhesion
      strength. METHODS: Study 1 involved four treatment groups: one with flaps made
      only with the FS laser (FS group), one with flaps made with the FS laser followed
      by excimer laser ablation (FS+LASIK), one with flaps made with the MM, and one
      with flaps made with the MM followed by excimer laser ablation (MM+LASIK). The
      eyes were analyzed by histology and TUNEL staining for apoptosis at 4 and 24
      hours. Study 2 involved two reference groups: an FS group and an MM group.
      Adhesion strength was measured with a tension meter 1 and 3 months later.
      RESULTS: Study 1: Inflammatory cell infiltration in the central cornea was
      significantly greater in the FS group than in the MM group at 4 and 24 hours (P <
      0.05) and was significantly greater in the FS+LASIK group than in the MM+LASIK
      group at 24 hours (P < 0.05). Infiltration at the peripheral interface was
      significantly greater in the FS group than in the MM group and was significantly
      greater in the FS+LASIK group than in the MM+LASIK group at 24 hours (P < 0.05).
      Study 2: At 1 and 3 months, 126.7 and 191.3 grams of force (gf) were needed to
      detach the flaps in the FS group, compared with 65 and 127.5 gf in the MM group,
      respectively. The grams of force needed was significantly higher in the FS group
      than in the MM group at 3 months (P < 0.05). CONCLUSIONS: The FS laser produces
      greater corneal stromal inflammation than the MM early postoperatively without
      any increase in apoptosis and stronger flap adhesion late postoperatively.
      Therefore, it may require stronger anti-inflammatory drugs to be administered.

PMID- 16431957
TI  - The effect of resection on satellite cell activity in rabbit extraocular muscle.
AB  - PURPOSE: A common treatment for motility disorders of the extraocular muscles
      (EOMs) is a resection procedure in which there is surgical shortening of the
      muscle. This procedure results in rotation of the globe toward the resected
      muscle, increased resting tension across the agonist-antagonist pair, and
      stretching of the elastic components of the muscles. In the rabbit, due to
      orbital constraints and limited rotation, resection results in more significant
      stretch of the surgically treated muscle than the antagonist. This surgical
      preparation allows for the examination of the effects of surgical shortening of
      one rectus muscle and passive stretch of its ipsilateral antagonist. METHODS: The
      insertional 6 mm of the superior rectus muscles of adult rabbits were resected
      and reattached to the original insertion site. After 7 and 14 days, the animals
      were injected intraperitoneally with bromodeoxyuridine (BrdU) every 2 hours for
      12 hours, followed by a 24-hour BrdU-free period. All superior and inferior
      rectus muscles from both globes were examined for BrdU incorporation, MyoD
      expression, neonatal and developmental myosin heavy chain (MyHC) isoform
      expression, and myofiber cross-sectional area alterations. RESULTS: In the
      resected muscle and in the passively stretched antagonist muscle, there was a
      dramatic increase in the number of myofibers positive for neonatal MyHC and in
      the number of BrdU- and MyoD-positive satellite cells. The addition of BrdU
      positive myonuclei increased from 1 per 1000 myofibers in cross sections of
      control muscles to 2 to 3 per 100 myofibers in the resected muscles. Single
      myofiber reconstructions showed that multiple BrdU-positive myonuclei were added
      to individual myofibers. Addition of new myonuclei occurred in random locations
      along the myofiber length of single fibers. There was no correlation between
      myofibers with BrdU-positive myonuclei and neonatal MyHC isoform expression.
      CONCLUSIONS: Both active and passive stretch of the rectus muscles produced by
      strabismus surgery dramatically upregulated the processes of satellite cell
      activation, integration of new myonuclei into existing myofibers, and concomitant
      upregulation of immature myosin heavy chain isoforms. Understanding the effects
      of strabismus surgery on muscle cell biological reactions and myofiber remodeling
      may suggest new approaches for improving surgical outcomes.

PMID- 16431958
TI  - The repeatability of best corrected acuity in normal and amblyopic children 4 to
      12 years of age.
AB  - PURPOSE: The main purpose of this work was to measure repeatability of line-by
      line logMAR (logarithm of the minimum angle of resolution) acuity in normal and
      amblyopic children, while adequately controlling for optical defocus. METHODS:
      The Lea Symbols Chart is a constant-crowding, equal-logMAR increment chart
      similar in design to the Early Treatment Diabetes Retinopathy Study [ETDRS]
      chart. LogMAR visual acuity was tested twice in each eye of 32 amblyopic and 11
      normal children. Each test commenced with screening in which one of the three
      central symbols was chosen for identification starting with the 1.0- or 0.9
      logMAR line, progressing to every second line until incorrect identification
      occurred. Symbol-by-symbol presentation then commenced at the logMAR line
      containing the last correctly identified symbol. The threshold was recorded as
      the last logMAR line where four of four or four of five correct responses
      occurred (i.e., line-by-line scoring). Retesting by the same examiner was
      identical and occurred within the same session. RESULTS: There was no significant
      difference in repeatability among normal, fellow, or amblyopic eyes. The
      difference between test and retest thresholds lay between +/-0.10 logMAR in 93%
      of eyes. The 95% limits of agreement for the difference was +/-0.18 logMAR.
      Repeatability in eyes tested first did not differ from that in those tested
      second in either the normal or amblyopic groups. CONCLUSIONS: In the age-group
      tested, the line-by-line method of threshold scoring compares favorably with
      previous reports of both line-by-line and interpolated threshold scoring. There
      was no clinically meaningful difference in repeatability between the normal and
      amblyopic children tested.

PMID- 16431959
TI  - A large GLC1C Greek family with a myocilin T377M mutation: inheritance and
      phenotypic variability.
AB  - PURPOSE: POAG is a complex disease; therefore, families in which a glaucoma gene
      has been mapped may carry additional POAG genes. The goal of this study was to
      determine whether mutations in the myocilin (MYOC) gene on chromosome 1 are
      present in two POAG families, which have previously been mapped to the GLC1C
      locus on chromosome 3. METHODS: The three exons of MYOC were screened by
      denaturing (d)HPLC. Samples with heteroduplex peaks were sequenced. Clinical
      findings were compared with genotype status in all available family members over
      the age of 20 years. RESULTS: A T377M coding sequence change in MYOC was
      identified in family members of the Greek GLC1C family but not in the Oregon
      GLC1C family. Individuals carrying both the MYOC T377M variant and the GLC1C
      haplotype were more severely affected at an earlier age than individuals with
      just one of the POAG genes, suggesting that these two genes interact or that both
      contribute to the POAG phenotype in a cumulative way.

PMID- 16431961
TI  - Semiquantitative optic nerve grading scheme for determining axonal loss in
      experimental optic neuropathy.
AB  - PURPOSE: To describe and evaluate a semiquantitative optic nerve grading scheme
      for assessing axonal loss in endothelin (ET)-1-induced chronic optic neuropathy.
      METHODS: Optic nerve cross-sections from both eyes of 39 Brown Norway rats
      unilaterally treated with various concentrations of ET-1 or physiological saline
      solution via a surgically implanted osmotic minipump were processed for light and
      transmission electron microscopy (TEM). The optic nerve damage grade, between 0
      (no damage) and 10 (total damage), was based on the number of zones of
      approximately equal damage and the mean percentage of damage within each zone.
      Grading was performed under light microscopy by three observers and compared with
      axonal survival determined with TEM using two quantification methods: the
      sampling method, in which approximately 10% of the section was counted, and the
      full-count method, in which the whole section was counted (n = 12). Axonal
      survival was expressed as a ratio of axon counts in the experimental to control
      eye. Before these comparisons, the inter- and intraobserver agreement rates were
      determined in another group of 85 and 12 ET-1-treated animals, respectively.
      RESULTS: The interobserver kappa was 0.66 (95% confidence interval [CI]: 0.58
      0.74) for all eyes and 0.55 (95% CI: 0.43-0.67) for the experimental eyes only.
      The intraobserver kappa was 0.80, 0.81, and 0.80 for all 24 eyes and 0.60, 0.64,
      and 0.71 for experimental eyes only. The correlation between damage grade in the
      experimental eye and axonal survival using the TEM sampling method (Spearman's
      rho = -0.677 for all animals and -0.827 for the subset of animals with full
      counts only) was lower than that with the full-count method (Spearman's rho = 
      0.926). When axonal survival was less than 0.7, the sampling method always
      underestimated the extent of damage. CONCLUSIONS: The grading scheme had good
      inter- and intraobserver agreement, and high correlation with the TEM methods. It
      is a practical and time-saving method, requiring less than 1 minute per nerve and
      is an alternative to sampling methods that can yield significant errors.

PMID- 16431960
TI  - Assessment of neuroprotective effects of glutamate modulation on glaucoma-related
      retinal ganglion cell apoptosis in vivo.
AB  - PURPOSE: To assess the neuroprotective effects of different glutamate modulation
      strategies, with a nonselective (MK801) and a selective (ifenprodil) NMDA
      receptor antagonist and a metabotropic glutamate receptor agonist (mGluR Group
      II, LY354740), in glaucoma-related in vivo rat models of retinal ganglion cell
      (RGC) apoptosis. METHODS: RGC apoptosis was induced in Dark Agouti (DA) rats by
      staurosporine (SSP) treatment. Single agents MK801, ifenprodil, or LY354740, or
      MK801 and LY354740 combined, were administrated intravitreally at different
      doses. Eyes were imaged in vivo using a recently established technique and the
      results confirmed histologically. The most effective combined therapy regimen of
      MK801 and LY354740 was then assessed in a chronic ocular hypertension (OHT) rat
      model with application at 0, 1, and 2 weeks after OHT surgery and the effects
      assessed as described before. RESULTS: All strategies of glutamate modulation
      reduced SSP-induced-RGC apoptosis compared with the control, in a dose-dependent
      manner: MK801 (R2= 0.8863), ifenprodil (R2= 0.4587), and LY354740 (R2= 0.9094),
      with EC50s of 0.074, 0.0138, and 19 nanomoles, respectively. The most effective
      combination dose of MK801 and LY354740 was 0.06 and 20 nanomoles (P < 0.05),
      respectively, and the optimal timing of the therapy was 0 weeks after OHT surgery
      (P < 0.05). CONCLUSIONS: This novel SSP model was validated as a useful tool for
      screening neuroprotective strategies in vivo. Group II mGluR modulation may be a
      useful treatment for RGC death. Combination therapy optimized to limit neurotoxic
      effects of MK801 may be an effective neuroprotective approach in retinal
      degenerative disease. Furthermore, treatments that minimize secondary RGC
      degeneration may be most useful in glaucoma.

PMID- 16431962
TI  - Correlation of asymmetric glaucomatous visual field damage and water-drinking
      test response.
AB  - PURPOSE: To determine whether there is a correlation between asymmetric
      glaucomatous visual field (VF) damage and water-drinking test (WDT) response.
      METHODS: A retrospective analysis was conducted of VF and WDT data from 101
      patients with glaucoma in clinical therapy, who were receiving treatment with the
      same topical medication in both eyes, and asymmetric VF defect. Eyes were
      classified according to mean deviation (MD) into "better" and contralateral
      "worse" eyes. Maximum mean difference in basal IOP was 2 mm Hg between both eyes.
      The peak IOP and fluctuation obtained with the WDT were compared between both
      groups. For the statistical analysis, the Tukey post hoc multiple comparison test
      and paired t-test were used. RESULTS: Better and contralateral worse eyes
      presented mean MDs of -4.6 +/- 5.3 and -9.0 +/- 7.4 dB, respectively (P < 0.001).
      Mean basal IOPs were 13.9 +/- 3.3 and 13.9 +/- 3.1 mm Hg, respectively (P =
      0.67). Mean maximum IOPs after water ingestion were 16.5 +/- 3.8 mm Hg in the
      group with less severe VF defect and 17.2 +/- 4.1 mm Hg in the contralateral
      group with worse visual fields (P < 0.001). Mean fluctuation (maximum IOP -
      minimum IOP after water ingestion) was 3.6 +/- 1.8 and 4.4 +/- 2.2 mm Hg (P <
      0.001), respectively. CONCLUSION: Eyes with worse MDs presented higher IOP peaks
      and fluctuation after water ingestion. This study demonstrates a lower capacity
      of eyes with worse glaucomatous lesion to respond to a stimulus that leads to a
      transitory elevation of IOP.

PMID- 16431963
TI  - West Nile virus infection induces interferon signalling in human retinal pigment
      epithelial cells.
AB  - PURPOSE: In addition to neuroinvasive disease, West Nile virus (WNV) infection is
      frequently associated with self-limiting chorioretinitis and vitritis. However,
      the mechanisms of ophthalmic WNV infection are rarely investigated, in part
      because of the lack of reliable in vitro models. The authors therefore
      established the first model of ocular WNV infection and investigated interaction
      of WNV with IFN signal-transduction mechanisms. METHODS: Human retinal pigment
      epithelial (RPE) cells were infected with WNV strain NY385-99 at a multiplicity
      of infection of 5. Virus replication was evaluated by virus titers at different
      times after infection. The susceptibility of RPE cells to WNV infection was
      confirmed by transmission electron microscopy. IFN-beta expression was assessed
      by quantitative real-time PCR and by measurements of antiviral activity in cell
      culture supernatants. IFN signaling was evaluated by phosphorylation of
      transducer and activator of transcription 1 and 2 (STAT1/2) proteins, with
      immunoblot analysis. RESULTS: RPE cells appeared to be highly sensitive to WNV
      infection. Maximum viral titers were found 24 hours after infection, followed by
      a continuous decline during the course of infection. WNV infection of RPE cells
      was followed by increased IFN-beta expression associated with IFN signaling and
      subsequent inhibition of WNV replication. CONCLUSIONS: In this study, the first
      cell culture model of ophthalmic WNV infection was developed and characterized in
      RPE cells, and the molecular mechanisms of WNV infection were studied. The data
      suggest that WNV induces a general antiviral state in RPE cells. This general
      antiviral state correlates with WNV-induced IFN signaling in retinal cells.

PMID- 16431964
TI  - Inter- and intramolecular epitope spreading in equine recurrent uveitis.
AB  - PURPOSE: To test the hypothesis that inter- and intramolecular spreading to S
      antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP)-derived
      epitopes occurs in a spontaneous model of recurrent uveitis in the horse.
      METHODS: The immune response of eight horses with equine recurrent uveitis (ERU)
      was compared with that of five control horses with healthy eyes. Lymphocytes
      derived from peripheral blood (PBLs) were tested every 8 weeks for their
      reactivity against S-Ag and various S-Ag and IRBP-derived peptides for 12 to 39
      months (median, 22 months). During uveitic episodes, additional blood samples
      were analyzed. RESULTS: Intermolecular epitope spreading was detectable in all
      ERU cases during the study. Intramolecular spreading occurred in seven (of eight)
      horses with ERU. Fourteen relapses were analyzed during the observation period.
      Ten uveitic episodes were accompanied by neoreactivity to S-Ag or IRBP-derived
      peptides during the relapse. Shifts in the immune response profile were also
      detectable without any clinical signs of inflammation. Eye-healthy control horses
      were negative at all time points in the in vitro proliferation assays.
      CONCLUSIONS: Inter- and intramolecular spreading was detectable in a spontaneous
      model of recurrent uveitis. The shifts in immunoreactivity could account for the
      remitting-relapsing character of the disease.

PMID- 16431965
TI  - Roles of OX40 in the development of murine experimental allergic conjunctivitis:
      exacerbation and attenuation by stimulation and blocking of OX40.
AB  - PURPOSE: To investigate the roles of interaction between OX40 and OX40 ligand
      (OX40L) in the development of experimental allergic conjunctivitis (EC) in mice.
      METHODS: BALB/c mice actively immunized with short ragweed pollen (RW) were
      intraperitoneally injected on days 0, 2, 4, 6, and 8 with agonistic anti-OX40 Ab,
      blocking anti-OX40L Ab, or normal rat (nr)IgG. On day 10, the mice were
      challenged with RW in eye drops, and 24 hours later their conjunctivas, spleens,
      and blood were harvested for analyses. For examination of the effects of the Abs
      during the late induction (or effector) phase, actively immunized mice were
      treated with the Abs just before or at the same time as the challenge. In
      addition, splenocytes from RW-primed mice were transferred into syngeneic naive
      mice, and the recipients were treated with Abs twice (on days 2 and 4). On day 4,
      the mice were challenged with RW and evaluated. RESULTS: When the treatments were
      performed during the induction phase, anti-OX40 Ab treatment significantly
      increased clinical EC and eosinophil infiltration into the conjunctiva, whereas
      anti-OX40L Ab treatment significantly reduced eosinophil infiltration. Compared
      with splenocytes from nrIgG-treated mice, splenocytes from anti-OX40 Ab-treated
      mice proliferated vigorously against RW and produced significantly higher amounts
      of IL-2, -4, and -5 by RW stimulation but a significantly lesser amount of IFN
      gamma after Con A stimulation. In contrast, splenocytes from anti-OX40L Ab
      treated mice produced significantly less IL-5 with RW stimulation and IL-2 and IL
      5 with Con A stimulation, whereas significantly more IFN-gamma was induced by Con
      A stimulation. Treatment with anti-OX40 and anti-OX40L Abs during the late
      induction or effector phase of EC did not affect eosinophil infiltration.
      CONCLUSIONS: Blocking of the interaction between OX40 and OX40L in vivo inhibits
      the development of EC. In contrast, forced stimulation of OX40 in vivo
      significantly exacerbates EC by activating T cells, especially Th2 cells. These
      effects were noted only in the induction phase of EC, suggesting that the
      interaction between OX40 and OX40L is important in the generation of Th2 immune
      responses in the development of EC.

PMID- 16431966
TI  - Glucosamine sulfate inhibits TNF-alpha and IFN-gamma-induced production of ICAM-1
      in human retinal pigment epithelial cells in vitro.
AB  - PURPOSE: Glucosamine sulfate (GS) is a naturally occurring sugar that possesses
      some immunosuppressive effects in vitro and in vivo, but its mechanism is
      unknown. We investigated whether GS could modulate the proinflammatory cytokine
      induced expression of the gene for intercellular adhesion molecule (ICAM)-1, an
      inflammatory protein in human retinal pigment epithelial (RPE) cells. METHODS:
      ARPE-19 cells were used as a model to determine the effects of GS on the
      expression of the ICAM-1 gene upregulated by TNF-alpha or IFN-gamma, by Western
      blot analysis and semiquantitative reverse transcription polymerase chain
      reaction (RT-PCR). The activation and nuclear translocation of the nuclear
      factors NF-kappaB and STAT1 were evaluated by immunocytochemistry, Western blot
      analysis, and electrophoretic mobility shift assay (EMSA). RESULTS: Both TNF
      alpha and IFN-gamma increased the expression of ICAM-1 at the mRNA and protein
      levels in a time- and dose-dependent manner in ARPE-19 cells. GS effectively
      downregulated the TNF-alpha- or IFN-gamma-induced expression of ICAM-1 in the
      protein and mRNA level in a dose-dependent manner. GS further inhibited the
      nuclear translocation of p65 proteins in TNF-alpha and phosphorylated STAT1 in
      IFN-gamma-stimulated ARPE-19 cells. CONCLUSIONS: GS inhibits the expression of
      the ICAM-1 gene in ARPE-19 cell stimulated with TNF-alpha or IFN-gamma through
      blockade of NF-kappaB subunit p65 and nuclear translocation of STAT1. This study
      has demonstrated a potentially important property of GS in reducing ICAM-1
      mediated inflammatory mechanisms in the eye.

PMID- 16431967
TI  - Roles for KCC transporters in the maintenance of lens transparency.
AB  - PURPOSE: To determine whether the potassium chloride cotransporter (KCC) family
      is expressed in the rat lens and to ascertain whether the transporters are
      involved in the regulation of lens volume and transparency. METHODS: RT-PCR was
      performed on RNA extracted from fiber cells to identify members of the KCC family
      expressed in the lens. Western blot analysis and immunocytochemistry, using KCC
      isoform-specific antibodies, were used to verify expression at the protein level
      and to localize KCC isoform expression. Organ-cultured rat lenses were incubated
      in isotonic artificial aqueous humor (AAH) that contained either the KCC-specific
      inhibitor [(dihydronindenyl)oxy] alkanoic acid (DIOA), the KCC activator N
      ethylmaleimide (NEM), or the chloride channel inhibitor 5-nitro-2-(3
      phenylpropylamino) benzoic acid (NPPB) for up to 18 hours. Lens wet weight was
      monitored, and lens transparency and tissue morphology were recorded with dark
      field and confocal microscopy, respectively. RESULTS: Molecular experiments to
      characterize KCC isoform expression showed that KCC1, -3, and -4 were all
      expressed in the lens at both the transcript and protein levels and that KCC2 was
      not. Immunocytochemistry indicated that the three KCC isoforms exhibited distinct
      differentiation-dependent expression patterns, with KCC1 and -3 being restricted
      to the lens cortex, whereas KCC4 was found throughout the entire lens, including
      the lens core. In the lens cortex, most of the labeling for all KCC isoforms was
      cytoplasmic, whereas in the lens core, KCC4 labeling was associated with the
      membrane. Incubation of lenses in 100 microM DIOA for 18 hours caused lenses to
      increase their wet weight and induced a cortical opacity that was caused by
      extensive damage to peripheral fiber cells located up to 150 microm in from the
      lens capsule, whereas deeper fiber cells appeared unaffected by DIOA exposure.
      Lower concentrations of DIOA (10 microM) revealed that this damage was initiated
      primarily by the swelling of peripheral fiber cells. In contrast, NPPB-treated
      lenses exhibited a deeper zone (>100 microm) of cell damage that was initiated by
      the dilation of the extracellular space between fiber cells. Exposure of lenses
      to the KCC activator NEM caused cell shrinkage in peripheral fiber cells but
      extensive cell swelling in deeper fiber cells. Peripheral cell swelling caused a
      differential recruitment of KCC isoforms from a cytoplasmic pool to the plasma
      membrane. DIOA-induced cell swelling increased the association of KCC4 with
      membrane, whereas hypotonic cell swelling dramatically increased the association
      of KCC1 with the membrane. CONCLUSIONS: The rat lens expresses three KCC
      transporter isoforms (KCC1, -3, and -4) in a differentiation-dependent manner.
      Modulation of transporter activity and subcellular localization suggests that
      multiple KCC transporters mediate KCl efflux in peripheral fiber cells in a
      dynamic fashion. These results indicate that, in addition to Cl- channels, KCC
      transporters play a role in mediating a circulating flux of Cl- ions, which
      contributes to the maintenance of lens transparency through controlling the
      steady state volume of lens fiber cells.

PMID- 16431968
TI  - Myogenic tone and reactivity of rat ophthalmic artery in acute exposure to high
      glucose and in a type II diabetic model.
AB  - PURPOSE: To evaluate the effect of acute exposure to high glucose on myogenic
      tone and reactivity of the rat ophthalmic artery and to compare the observations
      with that in ophthalmic artery from a diabetic rat model. METHODS: Ophthalmic
      arteries from Sprague-Dawley rats were pressurized at 70 mmHg in an arteriograph,
      and outer diameter was monitored. Myogenic tone was assessed over a range of
      intraluminal pressures in the presence and absence of high glucose or mannitol.
      The effects of high glucose on reactivity to carbachol and phenylephrine were
      determined. Arteries from type II diabetic BBZDR/Wor rats and age-matched control
      rats were evaluated for myogenic tone and reactivity. RESULTS: Myogenic tone was
      enhanced by 25 mM, but decreased by 40 mM, glucose and was not affected by
      mannitol. Constriction to phenylephrine was not affected by 25 mM, but was
      decreased by 40 mM glucose, and carbachol-mediated dilation was unaffected.
      Effects of high glucose were not observed in the absence of endothelium.
      Miconazole, a nonselective inhibitor of cytochrome-P450 enzymes or dihydro
      ouabain, an inhibitor of Na+,K+-ATPase blocked the effect of 40 mM but not 25 mM
      glucose. Arteries from diabetic rats showed decreased myogenic tone compared with
      control arteries, and this decrease was not observed in the absence of
      endothelium. CONCLUSIONS: Acute exposure to high glucose has a concentration- and
      endothelium-dependent effect on the myogenic tone of rat ophthalmic artery.
      Attenuation of tone by high glucose is probably due to the activation of smooth
      muscle Na+,K+-ATPase by endothelial cytochrome-P450 metabolite. Pressure-mediated
      autoregulation in ophthalmic artery in type II diabetic BBZDR/Wor rat operates at
      lower resistance, probably due to hyperglycemia.

PMID- 16431969
TI  - Dilation of retinal arterioles in response to lactate: role of nitric oxide,
      guanylyl cyclase, and ATP-sensitive potassium channels.
AB  - PURPOSE: Lactate, a key metabolite in the retinal tissue, has been implicated in
      regulating retinal blood flow to match retinal metabolic demand. However, the
      direct effect of lactate on retinal vascular tone and the possible underlying
      signaling mechanisms remain unknown. In the present study, the roles of
      endothelium-derived vasodilators, guanylyl cyclase, and potassium channels were
      examined in lactate-induced dilation of retinal arterioles in vitro. METHODS:
      Porcine second-order retinal arterioles were isolated, cannulated, and
      pressurized to 55 cm H2O lumenal pressure without flow. Diameter changes in
      response to agonists were recorded with videomicroscopic techniques. RESULTS: All
      vessels developed basal tone (approximately 70 microm in internal diameter) and
      dilated dose dependently in response to neutralized L-lactate (0.01-10 mM).
      Inhibition of cyclooxygenase by indomethacin only slightly reduced the
      vasodilatory response to lactate. In contrast, blockade of monocarboxylate
      transporters, nitric oxide (NO) synthase, soluble guanylyl cyclase, and ATP
      sensitive potassium (KATP) channels nearly abolished lactate-induced
      vasodilation. The cGMP phosphodiesterase inhibitor zaprinast enhanced the
      vasodilation response to lactate. Similar to the lactate-induced response, the
      vasodilation elicited by S-nitroso-N-acetylpenicillamine, an NO donor that
      activates cGMP signaling, was also inhibited by the soluble guanylyl cyclase and
      KATP channel blockers. CONCLUSIONS: These data suggest that uptake of lactate by
      vascular cells via monocarboxylate transporters causes retinal arteriolar
      dilation predominantly via stimulation of NO synthase and subsequent activation
      of guanylyl cyclase. The guanylyl cyclase/cGMP signaling triggers opening of KATP
      channels for vasodilation. A better understanding of the fundamental signaling
      pathways responsible for lactate-induced dilation of retinal arterioles may help
      shed light on the possible mechanisms contributing to the metabolic regulation of
      retinal blood flow under physiological and pathophysiological conditions.

PMID- 16431970
TI  - Heat shock protein 90 is an essential molecular chaperone for nuclear transport
      of glucocorticoid receptor beta.
AB  - PURPOSE: Glucocorticoid sensitivity in glaucoma has been attributed to
      differences in the expression of the two glucocorticoid receptors, GRalpha and
      GRbeta. GRalpha undergoes steroid-dependent nuclear translocation by associating
      with a heat shock protein (Hsp)90 multiprotein heterocomplex. The nuclear
      transport of the non-ligand-binding GRbeta is still unknown. In this study, the
      roles of Hsp90 in the nuclear transport of GRbeta were investigated. METHODS:
      Immunocytochemistry and Western blot analysis were performed to detect the
      subcellular expression of GRbeta and Hsp90 in normal and glaucomatous trabecular
      meshwork (TM) cells, as well as in TM cells overexpressing GRbeta. The role of
      Hsp90 in GRbeta transport and stability were determined with the Hsp90 inhibitor,
      17-AAG and the proteasome inhibitor lactacystin. Coimmunoprecipitation was
      performed to study GRbeta-Hsp90 complexes. RESULTS: In normal and glaucomatous TM
      cells, the nuclear concentration of Hsp90 correlates with the nuclear expression
      of GRbeta. Transfection with a GRbeta expression construct produces an
      overexpression and accumulation of GRbeta in the nucleus with a corresponding
      increase in nuclear Hsp90 amount. 17-AAG, a specific Hsp90 inhibitor, completely
      blocks the nuclear accumulation of GRbeta and consequently leads to the
      degradation of GRbeta in proteasomes. Coimmunoprecipitation experiments verify
      that GRbeta complexes with Hsp90 and the microtubule motor protein dynein.
      CONCLUSIONS: These data provide strong evidence that Hsp90 is an essential
      molecular chaperone for the nuclear transport of GRbeta. This transport appears
      to occur along micotubular tracks. Because nuclear GRbeta is important in
      regulating the glucocorticoid responsiveness, changes in GRbeta nuclear transport
      could influence subsequent responses that are often seen clinically, such as
      glucocorticoid resistance in some inflammatory and autoimmune diseases or
      enhanced glucocorticoid sensitivity in glaucoma.

PMID- 16431971
TI  - Macular pigment shows ringlike structures.
AB  - PURPOSE: The spatial distribution of macular pigment is generally assumed to
      monotonously decrease to very low values in the periphery. However, there are
      indications that this picture may be too simple. The purpose of this study was to
      examine the spatial distribution of the macular pigment optical density. METHODS:
      Fundus reflectance and autofluorescence maps at 488 and 514 nm Argon laser
      wavelengths were acquired in 53 healthy subjects with a custom-built scanning
      laser ophthalmoscope. Because the lens and the macular pigment are the only
      absorbers in this wavelength region, digital subtraction of log reflectance and
      log autofluorescence at the two wavelengths provides density maps of the sum of
      both absorbers. RESULTS: In approximately half of the subjects, we observed a
      distinct ring pattern at a mean distance of 0.7 degrees of the fovea. In a few
      subjects, the ring had an even larger optical density than did the central peak.
      A simple model with an exponentially decaying density as a function of
      eccentricity, in combination with a Gaussian-distributed ring pattern, yielded a
      good description of the data for both methods. The widths of the central peak and
      the Gaussian ring, and also the eccentricity at which the ring peaks, were
      similar for both methods. The prominence of the ring did not depend on age and
      gender. CONCLUSIONS: Both reflectance and autofluorescence maps showed ring
      patterns in the distribution of the macular pigment, which probably follow the
      inner plexiform layer.

PMID- 16431972
TI  - Visual stimulus-induced changes in human near-infrared fundus reflectance.
AB  - PURPOSE: Imaging studies from anesthetized feline, primate, and human retinas
      have revealed near-infrared fundus reflectance changes induced by visible light
      stimulation. In the present study, the spatial and temporal properties of similar
      changes were characterized in normal, awake humans. METHODS: Five normal human
      subjects were studied. A modified fundus camera was used to image changes in
      retinal reflectance of 780-nm near-infrared light imaged onto a 12-bit charge
      coupled device (CCD) camera in response to a green (540 nm) visual stimulus.
      During 60 seconds of recording (frame rate, 3 Hz) 10 cycles were recorded, during
      each of which 3 seconds of blank and then 3 seconds of either vertical bar or
      blank stimulus was projected. The change in the average near-infrared reflectance
      of the stimulated retinal region relative to an equal-sized nonstimulated region
      (r is the ratio of reflectance between the two retinal areas) was analyzed with a
      mixed model for repeated measures. RESULTS: The mixed model showed a significant
      average decrease in r of 0.14% (95% CI, -0.25 to -0.03) over all subjects induced
      by bar stimulus cycles, with a gradual return to baseline after stimulus offset,
      compared with only a 0.04% (95% CI, -0.11-+0.20) decrease in r induced by blank,
      nonstimulated cycles. The mixed model for individuals showed a decreasing linear
      trend in r over time during bar stimulation, but no decrease for blank cycles in
      three of five subjects. CONCLUSIONS: There was a localized decrease in
      reflectance in response to 780-nm near-infrared light in the retinal region
      exposed to a visual stimulus, which was significant in three of five subjects. It
      is presumed that the reflectance change represents the functional activity of the
      retina in response to a visual stimulus.

PMID- 16431973
TI  - Toxicity of triamcinolone acetonide on retinal neurosensory and pigment
      epithelial cells.
AB  - PURPOSE: To study the toxicity of triamcinolone acetonide (Kenalog; Bristol
      Meyers Squibb, Princeton, NJ) on retinal pigment epithelial (ARPE-19) and retinal
      neurosensory (R28) cells. METHODS: ARPE-19 and R28 were grown in tissue culture
      in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum.
      Cells were treated with 50, 100, and 200 microg/mL concentration of triamcinolone
      acetonide for 2, 6, and 24 hours. The cells were also treated with the steroid
      without the vehicle and with the vehicle alone, in which triamcinolone acetonide
      was suspended. Toxicity was determined by trypan blue dye-exclusion and WST-1
      mitochondrial dehydrogenase assays. RESULTS: Vehicle alone did not reduce the
      viability of ARPE-19 or R28 cells and also did not affect the mitochondrial
      dehydrogenase activity of the cells. The mean cell viability of ARPE-19 and R28
      cells after exposure to triamcinolone acetonide with vehicle 200 microg/mL for 24
      hours was 70.7% +/- 10.61% and 75.35% +/- 12.42%, respectively compared with the
      untreated ARPE-19 (92.7% +/- 6.24%, P < 0.01) and R28 cells (90.63% +/- 5.62%, P
      < 0.001). The mean cell viability of ARPE-19 cells after exposure to
      triamcinolone acetonide (200 microg/mL) alone without the vehicle was 84.96% +/-
      0.32%, 85.2% +/- 3.26%, and 84.73% +/- 2.71% at 2, 6, and 24 hours, respectively,
      compared with the untreated ARPE-19 cells (P < 0.001). The R28 cells exposed to
      triamcinolone acetonide (200 microg/mL) without the vehicle also had a
      significant reduction in the mean cell viability at 24 hours (86.42% +/- 3.87%, P
      < 0.001) and 6 hours (89.03% +/- 1.01%, P < 0.01). There was a significant
      reduction in the mitochondrial dehydrogenase activity in the ARPE-19 cells when
      treated with both triamcinolone acetonide, with or without the vehicle at a
      concentration of 200 microg/mL at all time points (P < 0.01). R28 cells did not
      have any significant reduction in mitochondrial dehydrogenase activity when
      treated with triamcinolone acetonide without the vehicle at any of the doses, but
      there was a significant reduction when the R28 cells were treated with
      triamcinolone acetonide with vehicle (200 microg/mL) for 24 hours (P < 0.05).
      Triamcinolone acetonide with vehicle caused a greater reduction in cell viability
      and mitochondrial dehydrogenase activity than did triamcinolone without vehicle,
      in both cell lines, although the difference was not statistically significant.
      CONCLUSIONS: Triamcinolone acetonide is toxic to proliferating cells of retinal
      origin in vitro at doses normally used in clinical practice. The vehicle by
      itself appears to be nontoxic to the cells, but may have a potentiating effect on
      the cytotoxicity of triamcinolone acetonide. The results of this in vitro study
      cannot be directly extrapolated to clinical practice, but, based on these data,
      further studies may be warranted.

PMID- 16431974
TI  - Cigarette smoke-related oxidants and the development of sub-RPE deposits in an
      experimental animal model of dry AMD.
AB  - PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been
      proposed to be an important injury stimulus relevant to the accumulation of
      subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking
      is a major risk factor for AMD, and cigarette smoke-related tar contains high
      concentrations of a potent oxidant, hydroquinone (HQ). This study was an
      investigation of the effects of cigarette smoke (CS) and HQ in the development of
      sub-RPE deposits in an experimental mouse model. METHODS: Sixteen-month-old
      C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were
      divided into two major experimental groups, one to examine the effects of
      cigarette smoke and one to study the effects of a defined cigarette smoke
      component such as HQ. In the first group, mice eyes were exposed to blue-green
      light (positive controls) or to whole cigarette smoke. A third group with no
      intervention served as the negative control. In the second experimental group,
      animals received a purified diet with HQ (0.8%) with low or high fat content for
      4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes
      processed for transmission electron microscopy. RESULTS: As previously
      demonstrated by our laboratory and others, most mice fed an HFD without other
      oxidant exposure demonstrated normal morphology or, in a few cases, small nodular
      basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in
      the food demonstrated a variable degree of basal laminar deposits and diffusely
      thickened Bruch's membrane. The choriocapillaris endothelium was variably
      hypertrophic. CONCLUSIONS: Exposure to cigarette smoke or the smoke-related redox
      molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's
      membrane, and accumulation of deposits within Bruch's membrane. Smoke-related
      oxidants may be another oxidative injury stimulus to the choriocapillaris and
      RPE, and may explain the association between cigarette smoking and early AMD.

PMID- 16431975
TI  - Ontogeny of VEGF, IGF-I, and GH in neonatal rat serum, vitreous fluid, and retina
      from birth to weaning.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF), insulin-like growth factor
      (IGF)-I, and growth hormone (GH) are major regulators of physical growth, as well
      as normal and pathologic retinal development. Ocular tissues are protected by the
      blood-ocular barrier. This study was conducted to test the hypothesis that the
      ontogenic profiles of VEGF, IGF-I, and GH in the rat serum, vitreous fluid, and
      retina are compartment specific, and that the vitreous is a reservoir for retinal
      growth factors. METHODS: Sprague-Dawley rat pups were killed at birth (postnatal
      day [P]0) and at P7, P14, and P21. At death, serum, vitreous fluid, and retinal
      homogenates were analyzed for ontogeny of VEGF, IGF-I, and GH. RESULTS: VEGF
      levels were 10 times higher in the vitreous than in serum at all stages of
      development. Vitreous and serum VEGF levels progressively declined, with lowest
      concentrations at P21. Retinal VEGF levels increased with the highest
      concentration at P21. IGF-I levels in the vitreous decreased from P7 through P21.
      IGF-I levels in serum and retinal homogenates increased with advancing postnatal
      age. Although IGF-I levels were four times higher in the vitreous than in the
      retina at P0, equilibration was achieved at P21. GH levels in the vitreous were
      10 times lower than serum levels, were decreased at P14 and P21, and remained
      unchanged from P0 through P21 in the retina. CONCLUSIONS: VEGF and IGF-I act in
      concert to promote retinal development with the vitreous fluid as a reservoir.
      The ontogenic profiles of VEGF, IGF-I and GH in the serum and ocular compartments
      are specific. These differences should be considered when therapies for ROP are
      proposed.

PMID- 16431976
TI  - Recombinant AAV-transduced iris pigment epithelial cell transplantation may
      transfer vector to native RPE but suppress systemic dissemination.
AB  - PURPOSE: To determine whether adenoassociated virus (AAV) vectors transduced into
      iris pigment epithelial (IPE) cells and transplanted into the subretinal space of
      rats will transfer the AAV genome to the host cells and whether the vectors are
      disseminated systemically. METHODS: Recombinant (r)AAV was transduced into rat
      IPE cells and transplanted into the subretinal space of rats. For the control,
      rAAVs alone were injected subretinally. The transplanted IPE cells were detected
      by LacZ staining. Immunohistochemistry, electron microscopy, electroretinography,
      and fluorescein-dextran angiography were performed. DNA was extracted from
      various organs and blood and examined for the AAV genome by polymerase chain
      reaction. RESULTS: No toxicity from rAAV transduction was observed in vitro. LacZ
      was expressed in the transplanted cells 1 and 2 weeks after transplantation. At 4
      and 12 weeks, fewer transplanted cells were detected than at 1 week, and LacZ
      expression was occasionally detected at the level of host retinal pigment
      epithelial (RPE) cells. Expression was also detected in ciliary body epithelial
      cells. The electroretinograms and fluorescein-dextran angiography were only
      mildly altered. Significantly lower levels of AAV genome were detected in the
      organs and blood of rats receiving rAAV-IPE cell transplants than with direct
      intravenous injection of AAV vectors. CONCLUSIONS: AAV-mediated LacZ was
      expressed in the transplanted cells after subretinal transplantation, and the
      transplanted IPE cells may transfer the rAAV to host tissues, such as RPE cells,
      long after the transplantation. This method of gene delivery did not lead to
      systemic dissemination of the vectors.

PMID- 16431977
TI  - Effect of experimental glaucoma in primates on oscillatory potentials of the slow
      sequence mfERG.
AB  - PURPOSE: To determine the effect of experimental glaucoma in macaque monkeys on
      oscillatory potentials (OPs) in the slow-sequence multifocal electroretinogram
      (mfERG). METHODS: Photopic slow-sequence mfERGs were recorded from anesthetized
      adult macaque monkeys and normal human subjects. The stimulus consisted of 103
      equal-sized hexagons within 17 degrees of the fovea. The m-sequence was slowed,
      with 14 blank frames, approximately 200 ms, interleaved between flashes for
      monkeys and 7 blank frames, approximately 100 ms, for humans, to produce
      waveforms similar to the photopic full-field flash ERG. Recordings were made
      under control conditions (24 monkey eyes, 7 human) and after laser-induced
      experimental glaucoma in monkeys (n = 8). A Fourier fast transform [FFT] was used
      to determine the frequency ranges of the major OPs. OP amplitudes were quantified
      by using root mean square (RMS) for two-frequency bands in five horizontal and
      four vertical locations. Visual field defects were assessed using behavioral
      static perimetry. Full-field photopic flash ERGs also were recorded. RESULTS: OPs
      in two distinct frequency bands were discriminated in the monkey mfERG: fast OPs,
      with a peak frequency of 143 +/- 20 Hz, and slow OPs, with a peak at 77 +/- 8 Hz.
      There were similar findings in humans and with the flash ERG in monkeys. The fast
      OP RMS in monkey control eyes was significantly larger in temporal than nasal
      retina (P < 0.01) and in superior versus inferior retina (P < 0.05) as reported
      previously. The slow OP RMS was largest in the foveal region. Experimental
      glaucoma reduced fast OP RMS in all locations studied, even when visual field
      defects were moderate (MD = -5 to -10 dB; P < 0.05), whereas the slow OP RMS was
      reduced significantly primarily in the foveal region when field defects were
      severe (MD < -10 dB; P < 0.05). The fast OP RMS showed a moderate correlation
      with local visual field sensitivity and with local ganglion cell density
      (calculated from visual field sensitivity). For the slow OPs the correlation was
      much poorer. Consistent with previous studies, the photopic negative response
      (PhNR) amplitude was significantly reduced when the visual sensitivity was
      minimally affected. CONCLUSIONS: OPs in the ERG of primates fall in two frequency
      bands: fast OPs with a peak frequency around 143 Hz and slow OPs, with a peak
      frequency around 77 Hz. The fast OPs, which rely more on the integrity of retinal
      ganglion cells and their axons than do the slow OPs, have potential utility for
      monitoring the progression of glaucoma and the effects of treatment.

PMID- 16431978
TI  - Compensation comparison method for assessment of retinal straylight.
AB  - PURPOSE: Presently, no instrument or method exists that is generally accepted for
      routine clinical assessment of (functional) retinal straylight. Yet retinal
      straylight is the cause of major patient complaints, such as hindrance from glare
      and loss of contrast. It results from disturbances in the optical media that
      increase light-scattering over angles of 1 degrees to 90 degrees . Its assessment
      would help to decide whether to perform surgery for (early) cataract and would
      help in the evaluation of corneal or vitreal turbidity. METHODS: The
      psychophysical technique of the "direct compensation" method was adapted to make
      it suitable for routine clinical assessment. In the new approach, called
      "compensation comparison, " the central test field is subdivided into two half
      fields: one with and one without counterphase compensation light. The subject's
      task is a forced-choice comparison between the two half fields, to decide which
      half flickers more strongly. A theoretical form for the respective psychometric
      function was defined and experimentally verified in a laboratory experiment
      involving seven subjects, with and without artificially increased light
      scattering. The method was applied in a separate multicenter study. Its
      reliability was additionally tested with a commercial implement (C-Quant; Oculus
      Optikgerate, Wetzlar-Dutenhofen, Germany). RESULTS: A repeated-measures SD of
      0.07 log units was achieved, to be compared with differences in the young normal
      population of 0.4 log units and an increase with healthy aging by 0.5 log units
      at 80 years and by 1.0 or more log units with (early) cataract or corneal
      disturbances. Reliability was further found to be high when using the commercial
      version of the METHOD:  CONCLUSIONS: The compensation comparison method for
      measuring retinal straylight is suited for clinical use to diagnose patients with
      complaints caused by large angle light scattering in the eye such as early
      cataract.

PMID- 16431979
TI  - Pyrrolo-C as a fluorescent probe for monitoring RNA secondary structure
      formation.
AB  - Pyrrolo-C (PC), or 3-[beta-D-2-ribofuranosyl]-6-methylpyrrolo[2,3-d]pyrimidin
      2(3H)-one, is a fluorescent analog of the nucleoside cytidine that retains its
      Watson-Crick base-pairing capacity with G. Due to its red-shifted absorbance, it
      can be selectively excited in the presence of natural nucleosides, making it a
      potential site-specific probe for RNA structure and dynamics. Similar to 2
      aminopurine nucleoside, which base-pairs with uridine (or thymidine), PC's
      fluorescence becomes reversibly quenched upon base-pairing, most likely due to
      stacking interactions with neighboring bases. To test its utility as an RNA
      probe, we examined PC's fluorescent properties over a wide range of ionic
      strengths, pH, organic cosolvents, and temperatures. Incorporation of PC into a
      single-stranded RNA results in an approximately 60% reduction of fluorescence
      intensity, while duplex formation reduces the fluorescence by approximately 75%
      relative to the free ribonucleoside. We find that the fluorescence intensity of
      PC is only moderately affected by ionic strength, pH, and temperature, while it
      is slightly enhanced by organic cosolvents, making it a versatile probe for a
      broad range of buffer conditions. We demonstrate two applications for PC:
      fluorescent measurements of the kinetics of formation and dissociation of an
      RNA/DNA complex, and fluorescent monitoring of the thermal denaturation of the
      central segment of an RNA duplex. Taken together, our data showcase the potential
      of pyrrolo-C as an effective fluorescent probe to study RNA structure, dynamics,
      and function, complementary to the popular 2-aminopurine ribonucleoside.

PMID- 16431980
TI  - Characterization of multimeric complexes formed by the human PTB1 protein on RNA.
AB  - Polypyrimidine tract binding protein (PTB or hnRNP I) has several known functions
      in eukaryotic cells, including exon exclusion during alternative splicing events,
      mRNA stabilization, and regulation of viral translation and replication. PTB
      contains four RNA Binding Domains (RBDs, or RRMs), all of which can potentially
      bind RNA, but their roles in the various biological functions of PTB are not
      clear. We investigate the properties of the complexes formed by human PTB1 on two
      target RNAs: the rat GABAA receptor gamma2 subunit pre-mRNA and the Hepatitis C
      Virus 3' NonTranslated RNA. The GABA RNA contains four polypyrimidine tracts in
      the intron and exon, while the HCV NTR contains a 75-nt U-rich tract and a highly
      structured 3'-terminus. Electrophoretic mobility shift assays show that PTB1
      protein first binds to both RNAs with nanomolar affinities, but subsequent
      protein addition leads to formation of higher-order complexes. Stoichiometry
      experiments show that the ultimate complexes contain up to eight PTB1 proteins
      per RNA strand. Protein constructs containing two tandem RBDs also bind the two
      RNAs, but with different affinities and stoichiometries. Nuclease protection
      assays show that PTB1 protects the polypyrimidine tracts in the GABA RNA, as does
      a construct consisting of RBD3 and RBD4; however, a construct containing RBD1 and
      RBD2 enhances cleavage of bound RNA. The binding mechanisms of PTB1 are unique to
      the full-length protein; these modes appear to include direct association with
      the RNA as well as weaker intermolecular protein associations.

PMID- 16431981
TI  - Comparison of crystal structure interactions and thermodynamics for stabilizing
      mutations in the Tetrahymena ribozyme.
AB  - Although general mechanisms of RNA folding and catalysis have been elucidated,
      little is known about how ribozymes achieve structural stability at high
      temperature. A previous in vitro evolution experiment identified a small number
      of mutations that significantly increase the thermostability of the tertiary
      structure of the Tetrahymena ribozyme. Because we also determined the crystal
      structure of this thermostable ribozyme, we have for the first time the
      opportunity to compare the structural interactions and thermodynamic
      contributions of individual nucleotides in a ribozyme. We investigated the
      contribution of five mutations to thermostability by using temperature gradient
      gel electrophoresis. Unlike the case with several well-studied proteins, the
      effects of individual mutations on thermostability of this RNA were highly
      context dependent. The three most important mutations for thermostability were
      actually destabilizing in the wild-type background. A269G and A304G contributed
      to stability only when present as a pair, consistent with their proximity in the
      ribozyme structure. In an evolutionary context, this work supports and extends
      the idea that one advantage of protein enzyme systems over an RNA world is the
      ability of proteins to accumulate stabilizing single-site mutations, whereas RNA
      may often require much rarer double mutations to improve the stability of both
      its tertiary and secondary structures.

PMID- 16431983
TI  - Potential for alternative intron-exon pairings in group II intron RmInt1 from
      Sinorhizobium meliloti and its relatives.
AB  - Ribozyme constructs derived from group II intron RmInt1 of Sinorhizobium meliloti
      self-splice in vitro when incubated under permissive conditions, but exon
      ligation is unusually inefficient when the 5' exon is truncated close to the IBS2
      intron-binding site. One plausible explanation for this observation is the
      presence of an alternative intron-exon pairing between an intron segment that
      overlaps with the EBS2 exon-binding site and a 5' exon site located just distal
      of IBS2 relative to the splice junction. Strikingly, the existence of this
      pairing is supported by comparative sequence analysis of introns related to
      RmInt1.

PMID- 16431982
TI  - Dissection of Prp8 protein defines multiple interactions with crucial RNA
      sequences in the catalytic core of the spliceosome.
AB  - Current models of the core of the spliceosome include a network of RNA-RNA
      interactions involving the pre-mRNA and the U2, U5, and U6 snRNAs. The essential
      spliceosomal protein Prp8 interacts with U5 and U6 snRNAs and with specific pre
      mRNA sequences that participate in catalysis. This close association with crucial
      RNA sequences, together with extensive genetic evidence, suggests that Prp8 could
      directly affect the function of the catalytic core, perhaps acting as a splicing
      cofactor. However, the sequence of Prp8 is almost entirely novel, and it offers
      few clues to the molecular basis of Prp8-RNA interactions. We have used an
      innovative transposon-based strategy to establish that catalytic core RNAs make
      multiple contacts in the central region of Prp8, underscoring the intimate
      relationship between this protein and the catalytic center of the spliceosome.
      Our analysis of RNA interactions identifies a discrete, highly conserved region
      of Prp8 as a prime candidate for the role of cofactor for the spliceosome's RNA
      core.

PMID- 16431984
TI  - Evolutionary specialization of recoding: frameshifting in the expression of S.
      cerevisiae antizyme mRNA is via an atypical antizyme shift site but is still +1.
AB  - An autoregulatory translational shift to the +1 frame is required for the
      expression of ornithine decarboxylase antizyme from fungi to mammals. In most
      eukaryotes, including all vertebrates and a majority of the studied fungi/yeast,
      the site on antizyme mRNA where the shift occurs is UCC-UGA. The mechanism of the
      frameshift on this sequence likely involves nearly universal aspects of the
      eukaryotic translational machinery. Nevertheless, a mammalian antizyme frameshift
      cassette yields predominantly -2 frameshift in Saccharomyces cerevisiae, instead
      of the +1 in mammals. The recently identified endogenous S. cerevisiae antizyme
      mRNA has an atypical shift site: UGC-GCG-UGA. It is shown here that endogenous S.
      cerevisiae antizyme frameshifting is +1 rather than -2. We discuss how antizyme
      frameshifting in budding yeasts exploits peculiarities of their tRNA balance, and
      relate this to prior studies on Ty frameshifting.

PMID- 16431985
TI  - Characterization of a Trypanosoma brucei RNA cap (guanine N-7) methyltransferase.
AB  - The m7GpppN cap structure of eukaryotic mRNA is formed by the sequential action
      of RNA triphosphatase, guanylyltransferase, and (guanine N-7) methyltransferase.
      In trypanosomatid protozoa, the m7GpppN is further modified by seven methylation
      steps within the first four transcribed nucleosides to form the cap 4 structure.
      The RNA triphosphatase and guanylyltransferase components have been characterized
      in Trypanosoma brucei. Here we describe the identification and characterization
      of a T. brucei (guanine N-7) methyltransferase (TbCmt1). Sequence alignment of
      the 324-amino acid TbCmt1 with the corresponding enzymes from human (Hcm1),
      fungal (Abd1), and microsporidian (Ecm1) revealed the presence of conserved
      residues known to be essential for methyltransferase activity. Purified
      recombinant TbCmt1 catalyzes the transfer of a methyl group from S
      adenosylmethionine to the N-7 position of the cap guanine in GpppN-terminated RNA
      to form the m7GpppN cap. TbCmt1 also methylates GpppG and GpppA but not GTP or
      dGTP. Mutational analysis of individual residues of TbCmt1 that were predicted-on
      the basis of the crystal structure of Ecm1--to be located at or near the active
      site identified six conserved residues in the putative AdoMet- or cap-binding
      pocket that caused significant reductions in TbCmt1 methyltransferase activity.
      We also report the identification of a second T. brucei RNA (guanine N-7) cap
      methyltransferase (named TbCgm1). The 1050-amino acid TbCgm1 consists of a C
      terminal (guanine N-7) methyltransferase domain, which is homologous with TbCmt1,
      and an N-terminal guanylyltransferase domain, which contains signature motifs
      found in the nucleotidyl transferase superfamily.

PMID- 16431986
TI  - The role of the Brr5/Ysh1 C-terminal domain and its homolog Syc1 in mRNA 3'-end
      processing in Saccharomyces cerevisiae.
AB  - The cleavage/polyadenylation factor (CPF) of Saccharomyces cerevisiae is thought
      to provide the catalytic activities of the mRNA 3'-end processing machinery,
      which include endonucleolytic cleavage at the poly(A) site, followed by synthesis
      of an adenosine polymer onto the new 3'-end by the CPF subunit Pap1. Because of
      similarity to other nucleases in the metallo-beta-lactamase family, the Brr5/Ysh1
      subunit has been proposed to be the endonuclease. The C-terminal domain of Brr5
      lies outside of beta-lactamase homology, and its function has not been
      elucidated. We show here that this region of Brr5 is necessary for cell viability
      and mRNA 3'-end processing. It is highly homologous to another CPF subunit, Syc1.
      Syc1 is not essential, but its removal improves the growth of other processing
      mutants at restrictive temperatures and restores in vitro processing activity to
      cleavage/ polyadenylation-defective brr5-1 extract. Our findings suggest that
      Syc1, by mimicking the essential Brr5 C-terminus, serves as a negative regulator
      of mRNA 3'-end formation.

PMID- 16431987
TI  - Identification and characterization of RsmE, the founding member of a new RNA
      base methyltransferase family.
AB  - A variety of RNA methyltransferases act during ribosomal RNA maturation to modify
      nucleotides in a site-specific manner. However, of the 10 base-methylated
      nucleotides present in the small ribosomal subunit of Escherichia coli, only
      three enzymes responsible for modification of four bases are known. Here, we show
      that the protein encoded by yggJ, a member of the uncharacterized DUF558 protein
      family of predicted alpha/beta (trefoil) knot methyltransferases is responsible
      for methylation at U1498 in 16S rRNA. The gene is well-conserved across bacteria
      and plants, and likely performs the same function in other organisms. A yggJ
      deletion strain lacks the methyl group at U1498 as well as the specific
      methyltransferase activity. Moreover, purified recombinant YggJ specifically
      methylates m3U1498 in vitro. The deletion strain was unaffected in exponential
      growth in rich or minimal media at multiple temperatures, but it was defective
      when grown in competition with isogenic wild-type cells. Based on these data, we
      conclude that yggJ is the founding member of a family of RNA base
      methyltransferases, and propose that it be renamed rsmE.

PMID- 16431988
TI  - Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent
      polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA.
AB  - 1-Methyladenosine modification at position 58 of tRNA is catalyzed by a two
      subunit methyltransferase composed of Trm6p and Trm61p in Saccharomyces
      cerevisiae. Initiator tRNA (tRNAi(Met)) lacking m1A58 (hypomethylated) is
      rendered unstable through the cooperative function of the poly(A) polymerases,
      Trf4p/Trf5p, and the nuclear exosome. We provide evidence that a catalytically
      active Trf4p poly(A) polymerase is required for polyadenylation of hypomethylated
      tRNAi(Met) in vivo. DNA sequence analysis of tRNAi(Met) cDNAs and Northern
      hybridizations of poly(A)+ RNA provide evidence that nascent pre-tRNAi(Met)
      transcripts are targeted for polyadenylation and degradation. We determined that
      a mutant U6 snRNA and an aberrant form of 5S rRNA are stabilized in the absence
      of Trf4p, supporting that Trf4p facilitated RNA surveillance is a global process
      that stretches beyond hypomethylated tRNAi(Met). We conclude that an array of RNA
      polymerase III transcripts are targeted for Trf4p/ Trf5p-dependent
      polyadenylation and turnover to eliminate mutant and variant forms of normally
      stable RNAs.

PMID- 16431989
TI  - Distal regulation of alternative splicing by splicing enhancer in equine beta
      casein intron 1.
AB  - The complexity of cotranscriptional splicing is reflected in the coordinated
      interplay between various cis-elements and transacting factors. In this report,
      we demonstrated that a cis-element in intron 1 of the equine beta-casein gene
      (intronic splicing enhancer 1, ISE1) increases the inclusion of all weak exons in
      its pre-mRNA. The ISE1 also functioned on a hybrid transcript, which was
      transcribed from the alpha-globin promoter, where it increased the inclusion of
      the human fibronectin EDA exon and the beta-casein exon 5. The region of ISE1
      necessary for its function included the same sequence as is found in some exonic
      splicing enhancers. Since the ISE1 influenced the splicing of the entire
      transcript from intron 1, we propose a model for the cotranscriptional splicing
      of beta-casein mRNA, where the 5' end of the growing transcript remains
      associated with the C-terminal domain of RNA polymerase II. Thus, the ISE1
      remains in close proximity to the mRNA exit groove throughout transcription and
      influences all weak exons as soon as they are copied.

PMID- 16431990
TI  - Live high-train low associated with increased haemoglobin mass as preparation for
      the 2003 World Championships in two native European world class runners.
AB  - BACKGROUND: It is unclear whether world class endurance athletes, in contrast
      with less well trained subjects, increase their haemoglobin mass on a regimen of
      living high and training low (LHTL). OBJECTIVE: To assess whether haemoglobin
      mass increases in world class athletes on LHTL and whether this increase is
      associated with peak performance at a subsequent important competition. METHODS:
      Two Swiss world class runners (one 5000 m and one marathon) lived for 26 days (18
      hours a day) at an altitude of 2456 m and trained at 1800 m. This LHTL camp was
      the preparation for the World Athletic Championships taking place 27-29 days
      after the end of the camp. Haemoglobin mass and other haematological variables
      were measured before and after the LHTL camp. The performance parameter was the
      race times during that period. RESULTS: Haemoglobin mass increased by 3.9% and
      7.6%, and erythrocyte volume by 5.8% and 6.3%. The race times, as well as the
      ranking at the World Championships, indicated clearly improved performance after
      the LHTL camp. CONCLUSIONS: The results suggest that LHTL with an adequate dose
      of hypoxia can increase haemoglobin mass even in world class athletes, which may
      translate into improved performance at important competitions at sea level.

PMID- 16431992
TI  - Who says you cannot get published?

PMID- 16431991
TI  - Is it more effective for highly trained swimmers to live and train at 1200 m than
      at 1850 m in terms of performance and haematological benefits?
AB  - OBJECTIVES: The effects of living and training have not been compared at
      different altitudes in well trained subjects. METHODS: Nine international
      swimmers lived and trained for 13 days similarly at 1200 m (T1200) and 1850 m
      (T1850). The two altitude training periods were separated by six weeks of sea
      level training. Before and after each training trip, subjects performed, at an
      altitude of 1200 m, an incremental exercise test to exhaustion of 5 x 200 m swims
      and a maximal test over 2000 m. RESULTS: There was no difference in Vo(2)max
      after each training trip: the before values were 58.5 (5.6) and 60.4 (6.7)
      ml/kg/min and the after values were 56.2 (5.2) and 57.1 (4.7) ml/kg/min for T1200
      and T1850 respectively. The 2000 m performance had improved during T1200 (1476
      (34) to 1448 (45) seconds) but not during T1850 (1458 (35) v 1450 (33) seconds).
      Mean cell volume increased during T1850 (86.6 (2.8) to 88.7 (2.9) microm(3)) but
      did not change during T1200 (85.6 (2.9) v 85.7 (2.9) microm(3)). The proportion
      of reticulocytes decreased during T1200 (15.2 (3.8)% to 10.3 (3.4)%) and
      increased during T1850 (9.3 (1.6)% to 11.9 (3.5)%). CONCLUSIONS: The short term
      effects of 13 days of training at 1200 m on swimming performance appear to be
      greater than the same type of training for the same length of time at 1850 m. As
      mean cell volume and proportion of reticulocytes only increased during training
      at 1850 m, the benefits of training at this altitude may be delayed and appear
      later on.

PMID- 16431993
TI  - Monitoring of serum enzymes in sport.

PMID- 16431994
TI  - Exercise associated hyponatraemia: quantitative analysis to understand the
      aetiology.
AB  - BACKGROUND: The development of symptomatic hyponatraemia consequent on
      participation in marathon and ultraendurance races has led to questions about its
      aetiology and prevention. OBJECTIVES: To evaluate: (a) the assertion that sweat
      sodium losses cannot contribute to the development of hyponatraemia during
      endurance exercise; (b) the adequacy of fluid replacement recommendations issued
      by the International Marathon Medical Directors Association (IMMDA) for races of
      42 km or longer; (c) the effectiveness of commercial sports drinks, compared with
      water, for attenuating plasma sodium reductions. METHODS: A mathematical model
      was used to predict the effects of different drinking behaviours on hydration
      status and plasma sodium concentration when body mass, body composition, running
      speed, weather conditions, and sweat sodium concentration were systematically
      varied. RESULTS: Fluid intake at rates that exceed sweating rate is predicted to
      be the primary cause of hyponatraemia. However, the model predicts that runners
      secreting relatively salty sweat can finish ultraendurance exercise both
      dehydrated and hyponatraemic. Electrolyte-containing beverages are predicted to
      delay the development of hyponatraemia. The predictions suggest that the IMMDA
      fluid intake recommendations adequately sustain hydration over the 42 km distance
      if qualifiers-for example, running pace, body size-are followed. CONCLUSIONS:
      Actions to prevent hyponatraemia should focus on minimising overdrinking relative
      to sweating rate and attenuating salt depletion in those who excrete salty sweat.
      This simulation demonstrates the complexity of defining fluid and electrolyte
      consumption rates during athletic competition.

PMID- 16431996
TI  - Effect of lower limb massage on electromyography and force production of the knee
      extensors.
AB  - OBJECTIVE: To evaluate the effect of massage on force production and
      neuromuscular recruitment. METHODS: Ten healthy male subjects performed
      isokinetic concentric contractions on the knee extensors at speeds of 60, 120,
      180, and 240 degrees /s. These contractions were performed before and after a 30
      minute intervention of either rest in the supine position or lower limb massage.
      Electromyography (EMG) and force data were captured during the contractions.
      RESULTS: The change in isokinetic mean force due to the intervention showed a
      significant decrease (p<0.05) at 60 degrees /s and a trend for a decrease (p =
      0.08) at 120 degrees /s as a result of massage compared with passive rest.
      However, there were no corresponding differences in any of the EMG data. A
      reduction in force production was shown at 60 degrees /s with no corresponding
      alteration in neuromuscular activity. CONCLUSIONS: The results suggests that
      motor unit recruitment and muscle fibre conduction velocity are not responsible
      for the observed reductions in force. Although experimental confirmation is
      necessary, a possible explanation is that massage induced force loss by
      influencing "muscle architecture". However, it is possible that the differences
      were only found at 60 degrees /s because it was the first contraction after
      massage. Therefore muscle tension and architecture after massage and the duration
      of any massage effect need to be examined.

PMID- 16431995
TI  - Adolescent flexibility, endurance strength, and physical activity as predictors
      of adult tension neck, low back pain, and knee injury: a 25 year follow up study.
AB  - OBJECTIVE: To examine whether adolescent flexibility, endurance strength, and
      physical activity can predict the later occurrence of recurrent low back pain,
      tension neck, or knee injury. METHODS: In 1976, 520 men and 605 women
      participated in a sit and reach test (flexibility) and a 30 second sit up test
      (endurance strength). In 1976 and 2001 (aged 37 and 42 years) they completed a
      questionnaire. Lifetime occurrence and risk of self reported low back pain and
      self reported, physician diagnosed tension neck and knee injury were calculated
      for subjects divided into tertiles by baseline results of strength and
      flexibility tests. RESULTS: Men from the highest baseline flexibility tertile
      were at lower risk of tension neck than those from the lowest tertile (odds ratio
      (OR) 0.51, 95% confidence interval (CI) 0.28 to 0.93). Women from the highest
      baseline endurance strength tertile were at lower risk of tension neck than those
      from the lowest tertile (OR 0.60, 95% CI 0.40 to 0.91). Men from the highest
      baseline endurance strength tertile were at higher risk of knee injury than those
      from the lowest tertile (OR 1.96, 95% CI 1.05 to 3.64). Men who at school age
      participated in physical activity were at lower risk of recurrent low back pain
      (OR 0.61; 95% CI 0.42 to 0.88) than those who did not. CONCLUSIONS: Overall good
      flexibility in boys and good endurance strength in girls may contribute to a
      decreased risk of tension neck. High endurance strength in boys may indicate an
      increased risk of knee injury.

PMID- 16431997
TI  - Injuries in West Indies cricket 2003-2004.
AB  - OBJECTIVE: To analyse injuries in West Indies Cricket and compare them with those
      of other cricket playing nations. METHODS: Injuries between June 2003 and
      December 2004 were surveyed prospectively in all major matches of the West Indies
      Cricket Board. RESULTS: Most injuries occurred in the West Indies Test and one
      day international teams. Mean match injury incidence was 48.7 per 10,000 player
      hours in Test cricket, and 40.6 per 10,000 player-hours in one day international
      cricket, with injury prevalence of 11.3% and 8.1% respectively. In domestic
      cricket, the match injury incidence was 13.9 per 10,000 player-hours for first
      class cricket, and 25.4 per 10,000 player-hours in one day domestic competitions.
      There were more injuries on tour for the West Indies team than at home. The
      batsmen and fast bowlers sustained 80% of injuries, with many leading to long
      absence from the game, although many of these injuries were sustained while
      fielding. Most injuries were of the phalanges (22%) and the lumbar spine (20%)
      sustained mainly while fielding (including catching) and fast bowling
      respectively. CONCLUSIONS: Injuries in West Indies cricket may be reduced by (a)
      early detection and management of injuries on tour, (b) attention to fielding and
      catching techniques, and (c) monitoring of young fast bowlers.

PMID- 16431998
TI  - Serum concentrations of C reactive protein, alpha1 antitrypsin, and complement
      (C3, C4, C1 esterase inhibitor) before and during the Vuelta a Espana.
AB  - OBJECTIVES: To determine serum concentrations of proinflammatory (C reactive
      protein, complement C3 and C4) and anti-inflammatory (alpha(1) antitrypsin, C1
      esterase inhibitor (C1-INH)) acute phase proteins in elite cyclists before and
      during a three week cycle tour. METHODS: Seventeen professional cyclists
      participating in the Vuelta a Espana volunteered for the study. Their mean (SD)
      physical characteristics were: age 28 (1) years; height 1.7 (0.06) m; weight 65
      (7) kg; body fat 7.6 (0.8)%; Vo(2)max 75.3 (2.3) ml/kg/min. Venepuncture was
      performed on each subject 24 hours before the tour began (T0), on day 11 (the
      first rest day; T1) and day 21 (the second to last stage of the tour; T2).
      Samples at T1 and T2 were taken about 17 hours after the previous stage. Analysis
      of variance was used to determine changes over time. Where significance was
      found, a Tukey post hoc test was performed. RESULTS: C reactive protein
      concentrations were consistently within the normal range, although there was a
      228%, non-significant increase at T1. C3 concentrations fell within the normal
      range at all times assessed. C4 concentrations before the race were within the
      normal range and were significantly increased 10 days (T1) into the race. C1-INH
      concentrations did not change significantly throughout the race. alpha(1)
      Antitrypsin concentration before the race was at the lower end of the normal
      range and was only significantly raised at T2. CONCLUSIONS: Although not as
      pronounced as those reported in marathon/ultramarathon runners, elite cyclists
      participating in a three week cycle tour experienced increases in selected
      proinflammatory and anti-inflammatory acute phase proteins, indicating an acute
      phase/inflammatory response. It is tenable that the increase in alpha(1)
      antitrypsin and C1-INH (anti-inflammatory mediators) at T2 served to attenuate
      the acute phase/inflammatory response. The lower than normal resting
      concentrations of the acute phase proteins supports the notion that chronic
      aerobic exercise induces an anti-inflammatory state.

PMID- 16431999
TI  - Converging evidence for the under-reporting of concussions in youth ice hockey.
AB  - BACKGROUND: Concussions are potentially serious injuries. The few investigations
      of prevalence or incidence in youth ice hockey have typically relied on
      prospective reports from physicians or trainers and did not survey players,
      despite the knowledge that many athletes do not report probable concussions.
      OBJECTIVE: This study sought to compare concussion rates in youth ice hockey that
      were estimated from a variety of reporting strategies. METHODS: Rates were
      calculated from British Columbia Amateur Hockey Association (BCAHA) official
      injury reports, from direct game observation by minor hockey volunteers (such as
      coaches and managers), as well as from retrospective surveys of both elite and
      non-elite youth players. All research was conducted within the BCAHA. RESULTS:
      Estimates from official injury reports for male players were between 0.25 and
      0.61 concussions per 1000 player game hours (PGH). Concussion estimates from
      volunteer reports were between 4.44 and 7.94 per 1000 PGH. Player survey
      estimates were between 6.65 and 8.32 per 1000 PGH, and 9.72 and 24.30 per 1000
      PGH for elite and non-elite male youth hockey, respectively. CONCLUSION: It was
      found that concussions are considerably under-reported to the BCAHA by youth
      hockey players and team personnel.

PMID- 16432000
TI  - Thermoregulatory observations in soccer match play: professional and recreational
      level applications using an intestinal pill system to measure core temperature.
AB  - BACKGROUND: Technological limitations associated with oesophageal and rectal
      temperature probes have previously limited match play observations of body
      temperature. OBJECTIVE: To investigate the application of an intestinal pill
      system to measure core temperature during dynamic, field based, soccer matches.
      METHODS: Core temperature (T(c)) was assessed using the intestinal pill system
      (CorTemp 2000) and changes in plasma volume were calculated using the values for
      haemoglobin and packed cell volume obtained before and after recreational (n = 8)
      and the professional soccer (n = 7) matches. RESULTS: In the recreational match,
      there were significant post-match reductions in body mass (-1.6%, p<0.05) and
      plasma volume (-7.2%, p<0.01). Significant increases were observed in T(c) from
      rest to half time (p<0.01) and from half time to full time (p<0.05). In the
      professional match, body mass decreased by 1.9% (p<0.05) and plasma volume by
      11.6% (p<0.01). T(c) increased from rest to half time (p<0.01) but was unchanged
      from half time to full time. Significant associations were observed between
      maximum oxygen consumption and match play heart rates in the second half of each
      match but these were not related to changes in plasma volume or T(c).
      CONCLUSIONS: Intestinal temperature proved a useful method of recording core
      temperature during soccer match play and assisted in the measurement of
      alterations in thermoregulatory variables in response to both professional and
      recreational level soccer matches; however, technological limitations still
      restrict the wider application of this method, especially at a competitive level.

PMID- 16432001
TI  - Optimising a curriculum for clinical haematology and biochemistry in sports
      medicine: a Delphi approach.
AB  - OBJECTIVES: To investigate issues of curriculum in the context of a postgraduate
      sports medicine training programme, specifically in the field of clinical
      biochemistry and haematology. METHODS: Following the Delphi methodology, a series
      of sequential questionnaires was administered to curriculum developers, clinical
      teachers, examiners, and registrars. RESULTS: Agreement on a core syllabus for
      this subject with an indication of the core aims and objectives of teaching and
      learning in this field and the associated required skills and competencies. An
      indication of current and ideal teaching and learning methods and reasons for
      these preferences. A consensus of key features of a teaching module for this
      field and of appropriate methods of examination. CONCLUSIONS: The data derived
      from this study, as well as the experience of engaging in it, will better inform
      curriculum developers, teachers, and students of one another's perceptions as to
      what is important in and appropriate to teaching and learning in this field of
      sports medicine. Engagement in the exercise and broader consideration of the
      outcomes by those who develop the curriculum, teach, and formulate the
      examination process will facilitate attainment of the ideal of well aligned
      teaching, learning, and examination in this specific field.

PMID- 16432003
TI  - Quantifying the functional rehabilitation of injured football players.
AB  - OBJECTIVE: To determine whether quantified, auditable records of functional
      rehabilitation can be generated using subjective assessments of players'
      performance in fitness tests routinely used in professional football. METHOD: Ten
      sequential test elements grouped into three phases (fitness, ball and match
      skills, match pace football) were used to monitor players' functional recovery
      from injury. Physiotherapists subjectively assessed players' performance in each
      test element using a six point subjective rating scale. Satisfactory performance
      in each element of the assessment programme added 10% to the injured player's
      recovery score. Daily recovery scores for injured players were recorded against
      the time spent in functional rehabilitation. RESULTS: Rehabilitation data for 118
      injuries sustained by 55 players over two seasons were recorded. The average time
      in functional rehabilitation depended on the time spent in pre-functional
      rehabilitation and the nature and location of injury. Benchmark functional
      rehabilitation curves (y = mln(x) + c) were developed for thigh (n = 15) and
      lower leg (n = 8) muscle strains and knee (n = 7) and ankle (n = 9) ligament
      sprains (R(2) = 0.95-0.98). CONCLUSIONS: A structured, quantified rehabilitation
      programme based on routine fitness and skills exercises and a graded subjective
      assessment of performance provides an auditable record of a player's functional
      recovery from a range of lower limb injuries and a transparent exit point from
      rehabilitation. The proposed method provides a permanent record of the functional
      rehabilitation of players' injuries and evidence based data to support
      management's return to play decisions.

PMID- 16432002
TI  - Growth hormone 1 (GH1) gene and performance and post-race rectal temperature
      during the South African Ironman triathlon.
AB  - BACKGROUND: Some studies have suggested that the insertion allele of the ACE gene
      is associated with endurance performance, including the Ironman triathlon. It is
      possible that this association is due to genetic linkage between the ACE I/D
      locus and the T/A variant in intron 4 of the neighbouring GH1 gene. The A variant
      is associated with lower levels of growth hormone production. Growth hormone has
      multiple effects, especially on metabolism during exercise and recovery from
      exercise. Its production during exercise has also been shown to stimulate sweat
      rate and heat loss. OBJECTIVE: To determine whether the GH1 gene is associated
      with the performance and/or post-race rectal temperatures of competitors in the
      South African Ironman triathlon. METHODS: A total of 169 of the fastest finishing
      white male triathletes who completed the 2000 and/or 2001 South African Ironman
      triathlon and 155 control subjects were genotyped for the T/A variant in the GH1
      gene. Post-race rectal temperature was also determined in 103 of these
      triathletes. RESULTS: There was no significant difference in the frequency of
      this polymorphism in the GH1 gene when the fastest finishing triathletes were
      compared with the control subjects. Post-race rectal temperatures were, however,
      significantly higher in those triathletes with an AA genotype (mean (SD) 37.7
      (0.8) degrees C) compared with those with a TT genotype (37.2 (0.8) degrees C) (p
      = 0.019). CONCLUSIONS: The T/A polymorphism in intron 4 of the GH1 gene was not
      associated with performance of the fastest finishers of the South African Ironman
      triathlon. Post-race rectal temperatures were, however, significantly higher in
      the fastest finishing athletes, who were homozygous for a GH1 genotype associated
      with lower growth hormone production.

PMID- 16432004
TI  - High risk of new knee injury in elite footballers with previous anterior cruciate
      ligament injury.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injury is a severe event for a
      footballer, but it is unclear if the knee injury rate is higher on returning to
      football after ACL injury. OBJECTIVE: To study the risk of knee injury in elite
      footballers with a history of ACL injury compared with those without. METHOD: The
      Swedish male professional league (310 players) was studied during 2001. Players
      with a history of ACL injury at the study start were identified. Exposure to
      football and all time loss injuries during the season were recorded
      prospectively. RESULTS: Twenty four players (8%) had a history of 28 ACL injuries
      in 27 knees (one rerupture). These players had a higher incidence of new knee
      injury of any type than the players without ACL injury (mean (SD) 4.2 (3.7) v 1.0
      (0.7) injuries per 1000 hours, p = 0.02). The risk of suffering a knee overuse
      injury was significantly higher regardless of whether the player (relative risk
      4.8, 95% confidence interval 2.0 to 11.2) or the knee (relative risk 7.9, 95%
      confidence interval 3.4 to 18.5) was used as the unit of analysis. No interactive
      effects of age or any other anthropometric data were seen. CONCLUSION: The risk
      of new knee injury, especially overuse injury, was significantly increased on
      return to elite football after ACL injury regardless of whether the player or the
      knee was used as the unit of analysis.

PMID- 16432005
TI  - Concussive head injury in children and adolescents related to sports and other
      leisure physical activities.
AB  - OBJECTIVE: To compare the characteristics of children and adolescents with
      concussive head injury (CHI) sustained during organised sports or other leisure
      physical activity. METHODS: This was a case series study reviewing the medical
      records retrospectively over a four year period of children 6-16 years presenting
      to the emergency department with a CHI after participating in sport and/or
      recreation activity. RESULTS: There were 592 cases of sport and recreation
      related concussion over the study period (2000-2003). Most of the patients (n =
      424, 71.6%) were male, with half (n = 304, 51.4%) being older than 10 years of
      age. A total of 152 (25.7%) cases of CHI were related to playing sports. Most
      cases (71.2%) were mild concussion. The cause of injury was a fall (n = 322,
      54.4%) or a collision. Nearly a quarter of the children (n = 143, 24.2%) were
      admitted to hospital, with imaging performed in 134 (22.7%). Most children were
      treated appropriately and no adverse events were reported. CONCLUSIONS: A severe
      CHI in a child is six times more likely to have resulted from organised sport
      than from other leisure physical activities. Outcomes for CHI in children is
      excellent, although their management places a considerable burden on emergency
      services. The need for activity restriction and the benefits of this in reducing
      long term cognitive effects of CHI are uncertain.

PMID- 16432006
TI  - No holds barred sport fighting: a 10 year review of mixed martial arts
      competition.
AB  - OBJECTIVE: To identify the most salient medical issues that may be associated
      with mixed martial arts competition by determining the types and proportions of
      match stoppages. METHODS: Publicly available video footage of 1284 men competing
      in 642 consecutive televised matches from November 1993 to November 2003 was
      reviewed to determine the reasons for which matches were stopped. Matches were
      sanctioned by either a United States or Japan based mixed martial arts
      organisation. RESULTS: Of the 642 matches, 182 (28.3+/-3.4%) were stopped because
      of head impact, 106 (16.5+/-2.9%) because of musculoskeletal stress, 91 (14.1+/
      2.7%) because of neck choke, 83 (12.9+/-2.6%) because of miscellaneous trauma,
      173 (27.0+/-3.4%) because of expiration of match time, and seven (1.0+/-0.8%)
      because of disqualification, where the values in parentheses are percentages+/
      95% confidence interval. CONCLUSIONS: Blunt force to the head resulted in the
      highest proportion of match stoppages. Further research is warranted to delineate
      the morbidity associated with participation in mixed martial arts.

PMID- 16432007
TI  - Dose-response relation between physical activity and sick leave.
AB  - OBJECTIVE: To investigate the dose-response relation between moderate and
      vigorous physical activity and sick leave in a working population. METHODS: Data
      were used from three large Dutch databases: two continuous, cross sectional
      surveys among a representative sample of the Dutch population and one prospective
      cohort study. A distinction was made between duration, frequency and intensity of
      physical activity. The outcome measure was the number of days of sick leave.
      Analyses of variance were used to compare sick leave (in days) for workers with
      different amounts of physical activity, in particular workers meeting the
      physical activity recommendations v those who did not. Linear and logistic
      regression analyses were used to obtain effect estimates in the prospective
      cohort study, with the generalised estimating equation (GEE) method. RESULTS: No
      relation was found between moderate physical activity and sick leave. In two
      databases, workers meeting the recommendation of vigorous physical activity
      (active at a vigorous level for at least three times a week) had significantly
      less sick leave: more than one day over two months and more than four days over a
      year. The duration of vigorous physical activity was not associated with sick
      leave. CONCLUSION: Physical activity at a vigorous intensity level for at least
      three times a week, as in the CDC/ACSM recommendation, has a positive effect on
      sick leave.

PMID- 16432008
TI  - Screening elite winter athletes for exercise induced asthma: a comparison of
      three challenge methods.
AB  - BACKGROUND: The reported prevalence of exercise induced asthma (EIA) in elite
      winter athletes ranges from 9% to 50%. Many elite winter athletes do not report
      symptoms of EIA. At present there is no gold standard test for EIA. OBJECTIVE: To
      establish the efficacy of screening for EIA and examine the role of the eucapnic
      voluntary hyperventilation (EVH) challenge and laboratory based and sport
      specific exercise challenges in the evaluation of elite winter athletes. METHODS:
      14 athletes (mean (SD) age 22.6 (5.7) years, height 177.2 (7.0) cm, body mass
      68.9 (16.9) kg) from the Great Britain short-track speed skating (n = 10) and
      biathlon teams (n = 4) were studied. Each athlete completed a laboratory based
      and sport specific exercise challenge as well as an EVH challenge, in randomised
      order. RESULTS: All 14 athletes completed each challenge. Two had a previous
      history of asthma. Ten (including the two with a previous history) had a positive
      test to at least one of the challenges. Ten athletes had a positive response to
      EVH; of these, only three also had a positive response to the sport specific
      challenge. No athletes had a positive response to the laboratory based challenge.
      CONCLUSIONS: Elite athletes should be screened for EIA. EVH is a more sensitive
      challenge in asymptomatic athletes than sport specific and laboratory based
      challenges. If sporting governing bodies were to implement screening programmes
      to test athletes for EIA, EVH is the challenge of choice.

PMID- 16432009
TI  - Is migraine a risk factor for the development of concussion?

PMID- 16432010
TI  - Human CD46-transgenic mice in studies involving replication-incompetent
      adenoviral type 35 vectors.
AB  - Wild-type strains of mice do not express CD46, a high-affinity receptor for human
      group B adenoviruses including type 35. Therefore, studies performed to date in
      mice using replication-incompetent Ad35 (rAd35) vaccine carriers may
      underestimate potency or result in altered vector distribution. Here, it is
      reported that CD46 transgenic mice (MYII-strain) express CD46 in all major organs
      and that it functions as a receptor for rAd35 vectors. Similar to monkeys and
      humans, MYII mice highly express CD46 in their lungs and kidneys and demonstrate
      low expression in muscle. Upon intravenous administration, rAd35 vector genomes
      as well as expression are detected in lungs of MYII mice, in contrast to wild
      type littermates. Expression was predominantly detected in lung epithelial cells.
      Upon intramuscular administration, the initial level of luciferase expression is
      higher in MYII mice as compared with wild-type littermates, in spite of the fact
      that CD46 expression is low in muscle of MYII mice. The higher level of
      expression in muscle of MYII mice results in prolonged gene expression as
      assessed by CCD camera imaging for luciferase activity. Finally, a significant
      dose-sparing effect in MYII mice as compared with wild-type littermates on anti
      SIVgag CD8+ T-cell induction following intramuscular vaccination with an
      rA35.SIVgag vaccine was observed. This dose-sparing effect was also observed when
      reinfusing dendritic cells derived from MYII mice after exposure to rAd35.SIVgag
      vaccine as compared with rAd35.SIVgag exposed dendritic cells from wild-type
      littermates. It was concluded that MYII mice represent an interesting preclinical
      model to evaluate potency and safety of rAd35 vectors.

PMID- 16432011
TI  - Neuropathogenesis of herpesvirus papio 2 in mice parallels infection with
      Cercopithecine herpesvirus 1 (B virus) in humans.
AB  - Cercopithecine herpesvirus 1 (monkey B virus; BV) produces extremely severe and
      usually fatal infections when transmitted from macaque monkeys to humans.
      Cercopithecine herpesvirus 16 (herpesvirus papio 2; HVP2) is very closely related
      to BV, yet cases of human HVP2 infection are unknown. However, following
      intramuscular inoculation of mice, HVP2 rapidly invades the peripheral nervous
      system and ascends the central nervous system (CNS) resulting in death, very much
      like human BV infections. In this study, the neurovirulence of HVP2 in mice was
      further evaluated as a potential model system for human BV infections. HVP2 was
      consistently neurovirulent when administered by epidermal scarification,
      intracranial inoculation and an eye splash. Quantitative real-time PCR,
      histopathology and immunohistochemistry were used to follow the temporal spread
      of virus following skin scarification and to compare the pathogenesis of
      neurovirulent and apathogenic isolates of HVP2. Apathogenic isolates were found
      to be capable of reaching the CNS but were extremely inefficient at replicating
      within the CNS. It is concluded that neurovirulent strains of HVP2 exhibit a
      pathogenesis in mice that parallels that observed in human BV infections and that
      this model system may prove useful in dissecting the viral determinants
      underlying the extreme severity of zoonotic BV infections.

PMID- 16432012
TI  - Human herpesvirus 6 envelope cholesterol is required for virus entry.
AB  - In this study, the role of cholesterol in the envelope of human herpesvirus 6
      (HHV-6) was examined by using methyl-beta-cyclodextrin (MbetaCD) depletion. When
      cholesterol was removed from HHV-6 virions with MbetaCD, infectivity was
      abolished, but it could be rescued by the addition of exogenous cholesterol. HHV
      6 binding was affected slightly by MbetaCD treatment. In contrast, envelope
      cholesterol depletion markedly affected HHV-6 infectivity and HHV-6-induced cell
      fusion. These results suggest that the cholesterol present in the HHV-6 envelope
      plays a prominent role in the fusion process and is a key component in viral
      entry.

PMID- 16432013
TI  - Effects of human papillomavirus type 16 oncoproteins on survivin gene expression.
AB  - Survivin has recently been identified as a novel member of the inhibitor of
      apoptosis (IAP) gene family. The product of this gene not only suppresses
      apoptosis but also controls cell division. Survivin is undetectable in most
      terminally differentiated normal tissues but is expressed in embryonic and fetal
      organs and is present in most malignant tumours. Human papillomaviruses (HPV) are
      thought to play an important role in the development of cervical cancer. By
      interfering in the cell cycle, the viral oncoproteins (E6 and E7) can induce the
      immortalization of the host cell. The transcriptional effects of the HPV-16 E6
      and E7 proteins on the survivin promoter in transiently transfected cell lines
      using luciferase tests were examined. HPV-16 E6, but not E7, was found to
      significantly transactivate the survivin promoter. Experiments performed in
      different cancer cell lines and with different E6 mutants indicated that the
      effect of E6 on the survivin promoter is largely dependent on p53 status. In
      accordance with this, the p53 tumour suppressor protein downregulated the
      expression of survivin. As E6 is able to interact with p53 and induces its
      ubiquitin-dependent degradation, it appears that the transactivation effect of E6
      on survivin is mediated by the p53 degradation pathway. Transduction of HPV-16 E6
      and E7 into human embryonic fibroblast cells showed that the HPV oncoproteins can
      upregulate endogenous survivin mRNA. Importantly, cell cycle synchronization
      experiments showed that the effect of HPV-16 E6 on survivin transcription is
      independent of the cell cycle.

PMID- 16432014
TI  - VP1 sequences of German porcine parvovirus isolates define two genetic lineages.
AB  - In order to evaluate the genetic variability of Porcine parvovirus (PPV), the
      complete capsid protein sequences (VP1/VP2) from seven recent field isolates from
      Germany, one isolate from the UK and one German vaccine strain were sequenced and
      analysed, along with two American (NADL-2 and Kresse), three Asian and 22
      Brazilian partial PPV sequences retrieved from GenBank. The analysis revealed a
      high degree of diversity: 1.2-2.6% at the nucleotide level and 1.2-6.8% at the
      amino acid level. Phylogenetic analysis defined two German clusters: one formed
      by four German isolates and the English, Asian and American sequences; and the
      second, distinct cluster formed by the other three of the seven German isolates
      examined. The latter cluster was still observed when the 22 partial sequences
      (853 nt of the 3' terminus of the VP2 gene) from the Brazilian isolates were
      included in the analyses, indicating that the VP2 sequence determines the
      phylogeny.

PMID- 16432015
TI  - Stability of the BK polyomavirus genome in renal-transplant patients without
      nephropathy.
AB  - To clarify the stability of the BK polyomavirus (BKPyV) genome in renal
      transplant (RT) recipients, three to five complete BKPyV genomes from each of six
      RT recipients with surviving renal allografts were molecularly cloned. The
      complete sequences of these clones were determined and compared in each patient.
      No nucleotide difference was detected among clones in two patients, and a few
      nucleotide variations were found among those in four patients. In each of these
      patients a parental sequence (usually the major sequence), from which variant
      sequences (usually minor sequences) with nucleotide substitutions would have been
      generated, were identified. A comparison between the parental and variant
      sequences in each patient identified a single nucleotide substitution in each
      variant sequence. From these findings, it was concluded that the genome of BKPyV
      is stable in RT recipients without nephropathy, with only minor nucleotide
      substitutions in the coding region.

PMID- 16432016
TI  - Novel mutation in Hepatitis B virus preventing HBeAg production and resembling
      primate strains.
AB  - Chronic carriers of hepatitis B infection often harbour virus strains with
      mutations in the precore region. These mutations are temporally associated with
      the development of HBeAg loss and seroconversion to anti-HBe. The most common
      precore mutation is a stop codon at position 1896, but other mutations leading to
      abolished HBeAg secretion have been described. Here, a novel precore mutation
      introducing a lysine in the precore position 28, a sequence shared by non-human
      primates but not by other human isolates, is described. However, the insertion
      causes a frame-shift preventing the expression of HBeAg by introducing a stop
      codon 5 aa downstream of the mutation. Analysis of the predicted RNA secondary
      structure indicates that the insertion could occur without fatally affecting the
      stability of the stem-loop encapsidation signal.

PMID- 16432017
TI  - Characterization and transcriptional analysis of protein tyrosine phosphatase
      genes and an ankyrin repeat gene of the parasitoid Glyptapanteles indiensis
      polydnavirus in the parasitized host.
AB  - Glyptapanteles indiensis (Braconidae, Hymenoptera) is an endoparasitoid of
      Lymantria dispar, the gypsy moth. Expression of G. indiensis polydnavirus (GiBV)
      encoded genes within the pest host results in inhibition of immune response and
      development and alteration of physiology, enabling successful development of the
      parasitoid. Here, GiBV genome segment F (segF), an 18.6 kb segment shown to
      encode nine protein tyrosine phosphatase (PTP) genes and a single ankyrin repeat
      gene (ank), is analysed. PTPs have presumed function as regulators of signal
      transduction, while ankyrin repeat genes are hypothesized to function in
      inhibition of NF-kappaB signalling in the parasitized host. In this study,
      transcription of each gene was mapped by 5'- and 3'-RACE (rapid amplification of
      cDNA ends) and temporal and tissue-specific expression was examined in the
      parasitized host. For polydnavirus gene prediction in the parasitized host, no
      available gene prediction parameters were entirely precise. The mRNAs for each
      GiBV segF gene initiated between 30 and 112 bp upstream of the translation
      initiation codon. All were encoded in single open reading frames (ORFs), with the
      exception of PTP9, which was transcribed as a bicistronic message with the
      adjacent ank gene. RT-PCR indicated that all GiBV segF PTPs were expressed early
      in parasitization and, for most, expression was sustained over the course of at
      least 7 days after parasitization, suggesting importance in both early and
      sustained virus-induced immunosuppression and alteration of physiology. Tissue
      specific patterns of PTP expression of GiBV segF genes were variable, suggesting
      differing roles in facilitating parasitism.

PMID- 16432018
TI  - Insertion and deletion analyses identify regions of non-structural protein 5A of
      Hepatitis C virus that are dispensable for viral genome replication.
AB  - Hepatitis C virus (HCV) non-structural protein 5A (NS5A) plays an essential role
      in viral genome replication. A series of transposon-mediated insertion mutants
      and deletion mutants of NS5A was used to examine the colony-forming ability of
      HCV subgenomic replicons encoding the mutant proteins. The results reveal that
      two regions of NS5A can tolerate insertions: one spanning residues 240-314, which
      contain the interferon sensitivity-determining region (ISDR), and the other
      spanning residues 349-417 at the carboxy terminus. The majority of these sites
      also tolerated insertion of enhanced green fluorescent protein. Furthermore,
      replicons encoding NS5A with deletions in ISDR or in the carboxy-terminal regions
      were replication-competent, indicating that these regions of NS5A are not
      necessary for replication. Taken together, the results suggest that the central
      region spanning the ISDR and the carboxy-terminal region of the molecule are
      dispensable for the functions of NS5A in viral genome replication.

PMID- 16432019
TI  - Biological, antigenic and phylogenetic characterization of the flavivirus Alfuy.
AB  - Alfuy virus (ALFV) is classified as a subtype of the flavivirus Murray Valley
      encephalitis virus (MVEV); however, despite preliminary reports of antigenic and
      ecological similarities with MVEV, ALFV has not been associated with human
      disease. Here, it was shown that ALFV is at least 10(4)-fold less neuroinvasive
      than MVEV after peripheral inoculation of 3-week-old Swiss outbred mice, but ALFV
      demonstrates similar neurovirulence. In addition, it was shown that ALFV is
      partially attenuated in mice that are deficient in alpha/beta interferon
      responses, in contrast to MVEV which is uniformly lethal in these mice. To assess
      the antigenic relationship between these viruses, a panel of monoclonal
      antibodies was tested for the ability to bind to ALFV and MVEV in ELISA. Although
      the majority of monoclonal antibodies recognized both viruses, confirming their
      antigenic similarity, several discriminating antibodies were identified. Finally,
      the entire genome of the prototype strain of ALFV (MRM3929) was sequenced and
      phylogenetically analysed. Nucleotide (73 %) and amino acid sequence (83 %)
      identity between ALFV and MVEV confirmed previous reports of their close
      relationship. Several nucleotide and amino acid deletions and/or substitutions
      with putative functional significance were identified in ALFV, including the
      abolition of a conserved glycosylation site in the envelope protein and the
      deletion of the terminal dinucleotide 5'-CU(OH)-3' found in all other members of
      the genus. These findings confirm previous reports that ALFV is closely related
      to MVEV, but also highlights significant antigenic, genetic and phenotypic
      divergence from MVEV. Accordingly, the data suggest that ALFV is a distinct
      species within the serogroup Japanese encephalitis virus.

PMID- 16432020
TI  - Non-structural proteins of dengue 2 virus offer limited protection to interferon
      deficient mice after dengue 2 virus challenge.
AB  - Chimeric (D2/WN) viruses containing the pre-membrane (prM) and envelope (E)
      proteins of West Nile virus (WN virus) and the capsid (C) and non-structural
      proteins of dengue 2 (DEN2) virus were used to evaluate the protective immunity
      elicited by either the flaviviral E protein or non-structural proteins. AG129
      interferon-deficient mice, previously shown to be protected against lethal DEN1
      or DEN2 viral infection after vaccination with a wild-type or candidate vaccine
      strain of DEN1 or DEN2 virus, respectively, were immunized with chimeric D2/WN
      virus and then challenged with DEN2 virus. D2/WN chimeric viruses were non
      pathogenic in AG129 mice. These viruses elicited little anti-DEN E antibody, high
      levels of anti-DEN NS1 antibody and no or very low levels of DEN2 virus
      neutralizing antibodies. Only 15% of D2/WN-immunized mice survived challenge with
      DEN2 virus. However, their mean survival time increased by 11-14 days over non
      immunized controls. These results suggest that, whilst the non-structural
      proteins were able to enhance mean survival times of AG129 mice, this protection
      was not as effective as protection mediated by the E protein.

PMID- 16432022
TI  - The mitochondrial pathway of apoptosis is triggered during feline calicivirus
      infection.
AB  - Feline calicivirus (FCV) belongs to the family Caliciviridae and is an important
      pathogen of the upper respiratory tract of cats. Recent studies have shown that
      cells infected with FCV undergo apoptosis, as evidenced by caspase activation,
      chromatin condensation and cleavage of poly(ADP-ribose) polymerase. Here, the
      upstream events were investigated in order to define the molecular mechanism of
      apoptosis in FCV-infected cells. It was shown that FCV induced translocation of
      phosphatidylserine to the cell outer membrane and release of cytochrome c from
      mitochondria at about 6-8 h post-infection. These events were preceded by the
      loss of mitochondrial membrane potential and Bax translocation from the cytosol
      to mitochondria between 4 and 6 h after infection. Release of cytochrome c from
      mitochondria triggered the activation of caspase-9 and the subsequent activation
      of the executioner caspase, caspase-3. These results suggest that the
      mitochondrial pathway of apoptosis is triggered during FCV infection.

PMID- 16432021
TI  - Characterization of the N-terminal domain of classical swine fever virus RNA
      dependent RNA polymerase.
AB  - To investigate RNA-dependent RNA polymerase (RdRp) further, mutational analysis
      of the N-terminal domain of the NS5B protein of Classical swine fever virus was
      performed. Results show that the N-terminal domain (positions 1-300) of the
      protein might be divided artificially into four different regions, N1-N4. The N1
      region (positions 1-61) contained neither conserved lysine nor conserved arginine
      residues. NS5B protein with deletion of the N1 region has the capacity for
      elongative RNA synthesis, but not for de novo RNA synthesis on natural templates.
      All substitutions of the conserved lysines and arginines in the N2 region
      (positions 63-216) destroyed RdRp activity completely. Substitutions of the
      conserved arginines in the N3 region (positions 217-280) seriously reduced RdRp
      activity. However, all substitutions of the conserved lysines in this region
      enhanced RNA synthesis and made the mutants synthesize RNA on any template.
      Substitutions of the conserved arginines in the N4 region (positions 281-300)
      reduced elongative synthesis and destroyed de novo RNA synthesis. In contrast,
      substitutions of lysines in this region did not affect RdRp activity
      significantly. These data indicate that the N3 region might be related to the
      enzymic specificity for templates, and the conserved lysines and arginines in
      different regions have different effects on RdRp activity. In combination with
      the published crystal structure of bovine viral diarrhea virus NS5B, these
      results define the important role of the N-terminal domain of NS5B for template
      recognition and de novo RNA synthesis.

PMID- 16432023
TI  - Analysis of protein-protein interactions in the feline calicivirus replication
      complex.
AB  - Caliciviruses are a major cause of gastroenteritis in humans and cause a wide
      variety of other diseases in animals. Here, the characterization of protein
      protein interactions between the individual proteins of Feline calicivirus (FCV),
      a model system for other members of the family Caliciviridae, is reported. Using
      the yeast two-hybrid system combined with a number of other approaches, it is
      demonstrated that the p32 protein (the picornavirus 2B analogue) of FCV interacts
      with p39 (2C), p30 (3A) and p76 (3CD). The FCV protease/RNA polymerase (ProPol)
      p76 was found to form homo-oligomers, as well as to interact with VPg and ORF2,
      the region encoding the major capsid protein VP1. A weak interaction was also
      observed between p76 and the minor capsid protein encoded by ORF3 (VP2). ORF2
      protein was found to interact with VPg, p76 and VP2. The potential roles of the
      interactions in calicivirus replication are discussed.

PMID- 16432025
TI  - Molecular-based reclassification of the bovine enteroviruses.
AB  - Bovine enteroviruses are currently classified into two serotypes within the
      species Bovine enterovirus (BEV). Comparison of the sequences of six American and
      eleven German BEV isolates with published BEV sequences revealed the necessity to
      revise the taxonomy of these viruses. Molecular data indicate that the bovine
      enteroviruses are composed of two clusters (designated BEV-A and -B) each with
      two and three geno-/serotypes, respectively. Whereas low amino acid identity of
      the capsid proteins 1C (VP3) and 1D (VP1) is the main criterion for the
      discrimination of geno-/serotypes, the BEV clusters, presumably representing
      species, differ in sequence identity of all viral proteins. In addition,
      characteristic lengths of (i) the capsid proteins 1B, 1C and 1D, (ii) the 2C
      protein, and (iii) the 3'-non-translated region are observed. The BEVs can be
      distinguished from the other enteroviruses by sequence identity and unique
      features of the 5'-non-translated region, i.e. a conserved second cloverleaf and
      characteristic RNA structures of the internal ribosome entry site.
      Phylogenetically, the closest relatives of the bovine enteroviruses are the
      porcine enteroviruses. Incongruent phylogenies of the 5'-non-translated region,
      the capsid proteins and the 3D polymerase indicate frequent intraserotypic and
      interserotypic recombination within the non-capsid and the capsid region of the
      BEV genome.

PMID- 16432024
TI  - Amino terminus of the SARS coronavirus protein 3a elicits strong, potentially
      protective humoral responses in infected patients.
AB  - The 3a protein of severe acute respiratory syndrome (SARS)-associated coronavirus
      is expressed and transported to the plasma membrane in tissue cells of infected
      patients. Its short N-terminal ectodomain was found to elicit strong humoral
      responses in half of the patients who had recovered from SARS. The ectodomain
      specific antibodies from the convalescent-phase plasma readily recognized and
      induced destruction of 3a-expressing cells in the presence of the human
      complement system, demonstrating their potential ability to provide immune
      protection by recognizing and eliminating SARS coronavirus-infected cells that
      express the target protein. In addition, when coupled to a carrier protein, the
      ectodomain peptide elicited 3a-specific antibodies in mice and rabbit at high
      titres. These results showed that the N terminus of the 3a protein is highly
      immunogenic and elicits potentially protective humoral responses in infected
      patients. Therefore, the short extracellular domain may be a valuable immunogen
      in the development of a vaccine for infectious SARS.

PMID- 16432026
TI  - Identification and genome characterization of Heliothis armigera cypovirus types
      5 and 14 and Heliothis assulta cypovirus type 14.
AB  - Genomic characterization of Heliothis armigera cypovirus (HaCPV) isolated from
      China showed that insects were co-infected with several cypoviruses (CPVs). One
      of the CPVs (HaCPV-5) could be separated from the others by changing the rearing
      conditions of the Heliothis armigera larvae. This finding was further confirmed
      by nucleotide sequencing analysis. Genomic sequences of segments S10-S7 from
      HaCPV-14, S10 and S7 from HaCPV-5, and S10 from Heliothis assulta CPV-14 were
      compared. Results from database searches showed that the nucleotide sequences and
      deduced amino acid sequences of the newly identified CPVs had high levels of
      identity with those of reported CPVs of the same type, but not with CPVs of
      different types. Putative amino acid sequences of HaCPV-5 S7 were similar to that
      of the protein from Rice ragged stunt virus (genus Oryzavirus, family
      Reoviridae), suggesting that CPVs and oryzaviruses are related more closely than
      other genera of the family Reoviridae. Conserved motifs were also identified at
      the ends of each RNA segment of the same virus type: type 14, 5'-AGAAUUU...CAGCU
      3'; and type 5, 5'-AGUU...UUGC-3'. Our results are consistent with classification
      of CPV types based on the electrophoretic patterns of CPV double-stranded RNA.

PMID- 16432027
TI  - The cytoplasmic domain of the F protein of Human respiratory syncytial virus is
      not required for cell fusion.
AB  - The cytoplasmic domains of the fusion proteins encoded by several viruses play a
      role in cell fusion and contain sites for palmitoylation associated with viral
      protein trafficking and virus assembly. The fusion (F) protein of Human
      respiratory syncytial virus (HRSV) has a predicted cytoplasmic domain of 26
      residues containing a single palmitoylated cysteine residue that is conserved in
      bovine RSV F protein, but not in the F proteins of other pneumoviruses such as
      pneumonia virus of mice, human metapneumovirus and avian pneumovirus. The
      cytoplasmic domains in other paramyxovirus fusion proteins such as Newcastle
      disease virus F protein play a role in fusion. In this study, it was shown that
      deletion of the entire cytoplasmic domain or mutation of the single cysteine
      residue (C550S) of the HRSV F protein had no effect on protein processing, cell
      surface expression or fusion.

PMID- 16432028
TI  - Design and preclinical evaluation of a multigene human immunodeficiency virus
      type 1 subtype C DNA vaccine for clinical trial.
AB  - In this study, the design and preclinical development of a multigene human
      immunodeficiency virus type 1 (HIV-1) subtype C DNA vaccine are described,
      developed as part of the South African AIDS Vaccine Initiative (SAAVI). Genetic
      variation remains a major obstacle in the development of an HIV-1 vaccine and
      recent strategies have focused on constructing vaccines based on the subtypes
      dominant in the developing world, where the epidemic is most severe. The vaccine,
      SAAVI DNA-C, contains an equimolar mixture of two plasmids, pTHr.grttnC and
      pTHr.gp150CT, which express a polyprotein derived from Gag, reverse transcriptase
      (RT), Tat and Nef, and a truncated Env, respectively. Genes included in the
      vaccine were obtained from individuals within 3 months of infection and selection
      was based on closeness to a South African subtype C consensus sequence. All genes
      were codon-optimized for increased expression in humans. The genes have been
      modified for safety, stability and immunogenicity. Tat was inactivated through
      shuffling of gene fragments, whilst maintaining all potential epitopes; the
      active site of RT was mutated; 124 aa were removed from the cytoplasmic tail of
      gp160; and Nef and Gag myristylation sites were inactivated. Following
      vaccination of BALB/c mice, high levels of cytotoxic T lymphocytes were induced
      against multiple epitopes and the vaccine stimulated strong CD8+ gamma interferon
      responses. In addition, high titres of antibodies to gp120 were induced in guinea
      pigs. This vaccine is the first component of a prime-boost regimen that is
      scheduled for clinical trials in humans in the USA and South Africa.

PMID- 16432029
TI  - Human immunodeficiency virus types 1 and 2 have different replication kinetics in
      human primary macrophage culture.
AB  - This study compares the replication of primary isolates of human immunodeficiency
      virus type 2 (HIV-2) and type 1 (HIV-1) in monocyte-derived macrophages (MDMs).
      Eleven HIV-2 and five HIV-1 primary isolates that use CCR5, CXCR4 or both
      coreceptors to enter cells were included. Regardless of coreceptor preference, 10
      of 11 HIV-2 viruses could enter, reverse transcribe and produce fully infectious
      virus in MDMs with efficiency equal to that in peripheral blood mononuclear
      cells. However, the kinetics of replication of HIV-2 compared with HIV-1 over
      time were distinct. HIV-2 had a burst of virus replication 2 days after infection
      that resolved into an apparent 'latent state' at day 3. HIV-1, however, continued
      to produce infectious virions at a lower, but steady, rate throughout the course
      of infection. These results may have implications for the lower pathogenesis and
      viral-load characteristics of HIV-2 infection.

PMID- 16432030
TI  - Influence of naturally occurring insertions in the fingers subdomain of human
      immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and
      mutation frequencies in vitro.
AB  - The fingers subdomain of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) is a hotspot for nucleoside analogue resistance mutations.
      Some multi-nucleoside analogue-resistant variants contain a T69S substitution
      along with dipeptide insertions between residues 69 and 70. This set of mutations
      usually co-exists with classic zidovudine-resistance mutations (e.g. M41L and
      T215Y) or an A62V mutation and confers resistance to multiple nucleoside analogue
      inhibitors. As insertions lie in the vicinity of the dNTP-binding pocket, their
      influence on RT fidelity was investigated. Commonly occurring insertion mutations
      were selected, i.e. T69S-AG, T69S-SG and T69S-SS alone, in combination with 3'
      azido-2',3'-deoxythymidine-resistance mutations M41L, L210W, R211K, L214F, T215Y
      (LAG(AZ) and LSG(AZ)) or with an alternate set where A62V substitution replaces
      M41L (VAG(AZ), VSG(AZ) and VSS(AZ)). Using a lacZalpha gapped duplex substrate,
      the forward mutation frequencies of recombinant wild-type and mutant RTs bearing
      each of the above sets of mutations were measured. All of the mutants displayed
      significant decreases in mutation frequencies. Whereas the dipeptide insertions
      alone showed the least decrease (4.0- to 7.5-fold), the VAG series showed an
      intermediate reduction (5.0- to 11.4-fold) and the LAG set showed the largest
      reduction in mutation frequencies (15.3- and 16.3-fold for LAG(AZ) and LSG(AZ),
      respectively). Single dNTP exclusion assays for mutants LSG(AZ) and LAG(AZ)
      confirmed their large reduction in misincorporation efficiencies. The increased
      in vitro fidelity was not due to excision of the incorrect nucleotide via ATP
      dependent removal. There was also no direct correlation between increased
      fidelity and template-primer affinity, suggesting a change in the active site
      that is conducive to better discrimination during dNTP insertion.

PMID- 16432031
TI  - Pns12 protein of Rice dwarf virus is essential for formation of viroplasms and
      nucleation of viral-assembly complexes.
AB  - Cytoplasmic inclusion bodies, known as viroplasms or viral factories, are assumed
      to be the sites of replication of members of the family Reoviridae.
      Immunocytochemical and biochemical analyses were carried out to characterize the
      poorly understood viroplasms of the phytoreovirus Rice dwarf virus (RDV). Within
      6 h of inoculation of cells, viroplasms, namely discrete cytoplasmic inclusions,
      were formed that contained the non-structural proteins Pns6, Pns11 and Pns12 of
      RDV, which appeared to be the constituents of the inclusions. Formation of
      similar inclusions in non-host insect cells upon expression of Pns12 in a
      baculovirus system and the association of molecules of Pns12 in vitro suggested
      that the inclusions observed in RDV-infected cells were composed basically of
      Pns12. Core proteins P1, P3, P5 and P7 and core virus particles were identified
      in the interior region of the inclusions. In contrast, accumulation of the outer
      capsid proteins P2, P8 and P9 and of intact virus particles was evident in the
      peripheral regions of the inclusions. These observations suggest that core
      particles were constructed inside the inclusions, whereas outer capsid proteins
      were assembled at the periphery of the inclusions. Viral inclusions were shown to
      be the sites of viral RNA synthesis by labelling infected cells with 5
      bromouridine 5'-triphosphate. The number of viroplasms decreased with time post
      inoculation as their sizes increased, suggesting that inclusions might fuse with
      one another during the virus-propagation process. Our results are consistent with
      a model, proposed for vertebrate reoviruses, in which viroplasms play a pivotal
      role in virus assembly.

PMID- 16432032
TI  - Zygocactus virus X-based expression vectors and formation of rod-shaped virus
      like particles in plants by the expressed coat proteins of Beet necrotic yellow
      vein virus and Soil-borne cereal mosaic virus.
AB  - Expression vectors were constructed from 35S promoter-containing full-length cDNA
      clones of Zygocactus virus X (ZVX). The expression of foreign genes was driven by
      the ZVX coat protein (cp) subgenomic promoter. It was successful only when the
      variable region downstream of the conserved putative promoter region
      GSTTAAGTT(X(12-13))GAA was retained. Most of the ZVX cp gene, except for a short
      3' part, was replaced by the corresponding sequence of the related Schlumbergera
      virus X (SVX) and its cp subgenomic promoter to enable encapsidation of the
      transcribed RNA by an SVX/ZVX hybrid cp. Vector-expressed cp of Beet necrotic
      yellow vein virus (BNYVV) assembled in Chenopodium quinoa, Tetragonia expansa and
      Beta vulgaris leaves into particles resembling true BNYVV particles. The virus
      produced from these constructs retained its ability to express BNYVV cp in local
      infections during successive passages on C. quinoa. This ability was lost,
      however, in the rarely occurring systemic infections.

PMID- 16432033
TI  - Biological properties of Beet mild yellowing virus derived from a full-length
      cDNA clone.
AB  - A German isolate of Beet mild yellowing virus (BMYV-IPP) was used for RT-PCR
      based construction of the first infectious full-length cDNA clone of the virus
      (BMYV(fl)). The complete genomic sequence was determined and displayed high
      similarity to the French isolate BMYV-2ITB. The host range of BMYV(fl) was
      examined by agroinoculation and aphid transmission. Both methods lead to systemic
      infections in Beta vulgaris, Nicotiana benthamiana, N. clevelandii, N. hesperis,
      Capsella bursa-pastoris and Lamium purpureum. Immunological investigation by
      tissue-print immunoassay (TPIA) of agroinoculated plant tissues revealed only
      local infections restricted to the agroinoculated mesophyll tissues in some plant
      species. In Nicotiana glutinosa and N. edwardsonii, BMYV was not found in either
      the agroinoculated tissue or distant tissues by TPIA. So far, BMYV(fl)
      agroinoculation did not extend or confine the BMYV host range known from aphid
      transmission experiments but it did describe new local hosts for BMYV.

PMID- 16432034
TI  - Host-induced avirulence of hibiscus chlorotic ringspot virus mutants correlates
      with reduced gene-silencing suppression activity.
AB  - Post-transcriptional gene silencing (PTGS) and virus-encoded gene-silencing
      suppressors are defence and counterdefence strategies developed by host and
      pathogens during evolution. Using a green fluorescence protein-based transient
      suppression system, the coat protein (CP) of Hibiscus chlorotic ringspot virus
      (HCRSV) was identified as a strong gene-silencing suppressor. CP suppressed sense
      RNA-induced but not dsRNA-induced local and systemic PTGS. This is different from
      another virus in the genus Carmovirus, Turnip crinkle virus (TCV), the CP of
      which strongly suppresses dsRNA-induced PTGS. HCRSV CP domain deletion mutants
      lost their suppression function, indicating that the complete CP is essential for
      suppression of PTGS. When CP was expressed from a Potato virus X (PVX) vector, it
      was able to enhance the symptom severity and to increase the accumulation of PVX
      RNA. Here, it is proposed that HCRSV CP suppresses PTGS at the initiation step,
      which is different from TCV CP. In addition, a previous study demonstrated that
      CP mutants resulting from serial passage of HCRSV in its local lesion host also
      showed a significantly reduced suppression function, indicating that host-induced
      mutations that lead to avirulence of HCRSV in kenaf correlate with its reduced
      ability to suppress PTGS.

PMID- 16432035
TI  - Identification and immuno-electron microscopy localization of p40, a protein
      component of immunosuppressive virus-like particles from Leptopilina heterotoma,
      a virulent parasitoid wasp of Drosophila.
AB  - Lamellocytes are specialized larval blood cells of Drosophila that carry out
      encapsulation of metazoan pathogens such as parasitoid wasps. Large virus-like
      particles (VLPs) from two closely related virulent parasitoid wasp species,
      Leptopilina heterotoma and Leptopilina victoriae, suppress the host encapsulation
      response by promoting lysis of lamellocytes. The molecular basis of VLP
      lamellocyte interaction and lamellocyte lysis is not understood. Here, it was
      shown that mature VLPs are composed of at least four major proteins. Polyclonal
      antisera against the most abundant L. heterotoma VLP protein, p40, cross-reacted
      with the most abundant L. victoriae VLP protein, p47.5. Immuno-electron
      microscopy (EM) of the long gland-reservoir complex revealed that p40 was
      expressed early in VLP biogenesis and was detected along with VLP precursors
      within the long gland cells and lumen. In the reservoir, VLPs had an angular
      core, resembled mature particles and p40 was detected outside the VLP cores.
      Immuno-EM staining of mature VLPs from both species localized the p40 and p47.5
      proteins largely to the periphery of the VLPs and along the VLP spike-like
      projections. p40 staining was observed in VLP-treated host haemocytes. In vitro,
      anti-p40 antibody almost completely blocked the ability of L. heterotoma VLPs to
      promote lamellocyte lysis. Anti-p40 antibody blocked lysis by L. victoriae VLPs
      by >50%. It is proposed that the VLP surface proteins p40 and p47.5 share
      antigenic determinants and significantly contribute to the strong virulence of
      their Hymenopteran hosts.

PMID- 16432036
TI  - Atypical prion protein in sheep brain collected during the British scrapie
      surveillance programme.
AB  - Scrapie of sheep and goats is the most common prion disease (or transmissible
      spongiform encephalopathy, TSE) of mammals and aggregates of abnormal, proteinase
      resistant prion protein (PrP(Sc)) are found in all naturally occurring prion
      diseases. During active surveillance of British sheep for TSEs, 29 201 sheep
      brain stem samples were collected from abattoirs and analysed for the presence of
      PrP(Sc). Of these samples, 54 were found to be positive by using an ELISA
      screening test, but 28 of these could not be confirmed initially by
      immunohistochemistry. These unconfirmed or atypical cases were generally found in
      PrP genotypes normally associated with relative resistance to clinical scrapie
      and further biochemical analysis revealed that they contained forms of PrP(Sc)
      with a relatively protease-sensitive amyloid core, some resembling those of Nor98
      scrapie. The presence of these atypical forms of protease-resistant PrP raises
      concerns that some TSE disorders of PrP metabolism previously may have escaped
      identification in the British sheep population.

PMID- 16432037
TI  - Pleiotropic effects of hydrogen peroxide in arteries and veins from normotensive
      and hypertensive rats.
AB  - Hydrogen peroxide causes vascular contraction and relaxation and contributes to
      the pathogenesis of hypertension. We hypothesized that the contractile state of
      blood vessels governs whether H2O2 causes contraction or relaxation. Hydrogen
      peroxide (1 micromol/L to 1 mmol/L) concentration-dependently contracted thoracic
      aorta and vena cava from sham normotensive and deoxycorticosterone acetate (DOCA)
      salt hypertensive rats. The maximal contraction to H2O2 was 3 times greater in
      DOCA aorta compared with sham aorta but unchanged in DOCA vena cava compared with
      sham vena cava. In prostaglandin F2alpha (20 micromol/L)-contracted aorta and
      vena cava from sham and DOCA rats, H2O2 (1 micromol/L to 1 mmol/L) induced a
      concentration-dependent relaxation that was impaired in DOCA aorta but not DOCA
      vena cava. In contrast, in KCl (30 mmol/L)-contracted vessels, maximal H2O2
      induced contraction was enhanced 15-fold in sham aorta and 5-fold in DOCA aorta
      but only 2-fold in sham vena cava. Tetraethylammonium (10 mmol/L), BAY K 8644
      (100 nmol/L), and ouabain (1 mmol/L) all enhanced maximal aortic H2O2-induced
      contraction, whereas only ouabain enhanced venous H2O2-induced contraction. The
      removal of extracellular Ca2+ reduced H2O2-induced contraction in KCl-contracted
      aorta, whereas maximal venous H2O2-induced contraction (under basal conditions)
      was unchanged. Our data suggest that differences in arterial and venous K+
      channel activity and extracellular Ca2+ influx are responsible for differences in
      arterial and venous contraction to H2O2. In DOCA-salt hypertension, arterial but
      not venous contraction to H2O2 is enhanced, and relaxation to H2O2 is reduced.

PMID- 16432038
TI  - Moderate ascorbate deficiency increases myogenic tone of arteries from pregnant
      but not virgin ascorbate-dependent rats.
AB  - Plasma ascorbic acid is decreased in women with the pregnancy disorder
      preeclampsia. We used a mutant strain of rats (Osteogenic Disorder Shionogi),
      dependent on dietary sources of vitamin C, to investigate whether reduced intake
      of the vitamin would differentially affect vascular function in late-pregnant
      (day 19) and age-matched virgin rats. The animals were given either 1 mg/mL of
      ascorbic acid ad libitum in drinking water [fully supplemented (FS)] or 0.25
      mg/mL [marginally supplemented (MS)]. Fetal weights were 21% lower in MS than FS
      rats, whereas mean maternal weights and pup numbers did not differ. Small
      mesenteric arteries (diameter, 268+/-7 microm) were mounted in a pressurized
      arteriograph. Myogenic reactivity (contractile response to step increases in
      intraluminal pressure) was increased in arteries from MS pregnant compared with
      FS pregnant rats to levels observed in virgin rats. Ascorbic acid intake did not
      affect myogenic responses of arteries from virgin rats. Hence, the normal
      pregnancy-induced reduction in myogenic reactivity was abrogated in MS pregnant
      animals. Inhibition of nitric oxide synthase had no effect on the myogenicity of
      arteries from virgin or MS pregnant rats but increased myogenicity of FS pregnant
      rats to the level of MS pregnant rats. Free radical scavengers reversed the
      accentuated myogenicity of MS pregnant rats without affecting FS pregnant or
      virgin rat arteries. These data indicate that moderate ascorbate deprivation
      increases mesenteric artery myogenic responsiveness during pregnancy. This
      increase may result from a decrease in nitric oxide-mediated modulation of the
      myogenic contractile response.

PMID- 16432039
TI  - Effects of aldosterone on the vasculature.

PMID- 16432040
TI  - Regulator of G-protein signaling-2 as a candidate gene: the road to hypertension
      or just another roadside marker?

PMID- 16432041
TI  - Polymorphisms and haplotypes of the regulator of G protein signaling-2 gene in
      normotensives and hypertensives.
AB  - Regulator of G protein signaling (RGS) proteins stimulate the GTPase activity of
      Galpha subunits of heterotrimeric G proteins, thereby negatively regulating G
      protein-coupled receptor signaling. RGS2, which preferentially alters Galphaq
      mediated signaling, may be important for cardiovascular health, because knockout
      of RGS2 in mice is associated with altered smooth muscle relaxation and
      hypertension. In this study, we determined genetic variation in the human RGS2
      gene by sequencing DNA in normotensive and hypertensive populations of whites
      (n=128) and blacks (n=122). We identified 14 single nucleotide polymorphisms and
      2 two-base insertion/deletions (in/del; 1891 to 1892 TC and 2138 to 2139 AA).
      Although most of the genetic variants were found at low allelic frequency, in
      particular in coding regions, the 1891 to 1892 TC and 2138 to 2139 AA intronic
      in/del were in linkage disequilibrium and were associated with hypertension in
      blacks (P<0.05). We defined several haplotypes for the RGS2 gene, certain of
      which showed striking differences between whites and blacks. Additionally, 2
      haplotypes had significantly different frequencies between hypertensive and
      normotensive black groups (P<0.05). We conclude that RGS2 is genetically
      conserved within coding regions but that the intronic in/del define ethnicity
      specific haplotypes. Moreover, certain RGS2 variants that occur at greater
      frequency in hypertensive blacks may serve as ethnicity-specific genetic variants
      for this disease.

PMID- 16432042
TI  - A longitudinal study of hypertension risk factors and their relation to
      cardiovascular disease: the Strong Heart Study.
AB  - This study estimated hypertension incidence and explored hypertension risk
      factors and their association with cardiovascular disease. Data collected from
      4549 American Indian participants in the 3 exams of the Strong Heart Study were
      used. Hypertension was defined as systolic blood pressure > or =140 mm Hg,
      diastolic blood pressure > or =90 mm Hg, or current use of antihypertensive
      medication. Generalized linear models were used to identify the risk factors for
      hypertension and the correlates of blood pressures. Cox proportional models with
      time-dependent covariates and the mixed models were used to explore the
      association of hypertension with cardiovascular disease. There was no sex
      difference in hypertension. After adjustment for other risk factors, the risks of
      developing hypertension among subgroups in each characterized group were as
      follows: prehypertensive versus normotensive, 3.21 times; macroalbuminuria and
      microalbuminuria versus normal, 3.47 and 1.72; diabetic versus nondiabetic, 1.56;
      overweight and obese versus normal weight, 1.30 and 1.51; and current alcohol
      drinking versus not, 1.22. Moreover, systolic blood pressure was significantly
      and positively associated with age, obesity, and albuminuria and negatively with
      smoking. After adjusting all other risk factors, those pretreated, untreated,
      controlled, and uncontrolled hypertensive participants had &1.74, 1.81, 2.19, and
      2.77 times higher risks of developing cardiovascular disease compared with
      normotensive participants, respectively. In 45- to 74-year-old American Indians,
      the risk of developing hypertension was rising. Prehypertensive participants had
      3.2/1.74 times higher risk of developing hypertension/cardiovascular disease than
      normotensive participants. Age, diabetes, and macro/microalbuminuria were
      independently significant risk factors of both hypertension and cardiovascular
      disease.

PMID- 16432043
TI  - From 24-hour blood pressure measurements to arterial stiffness: a valid short
      cut?

PMID- 16432044
TI  - Epithelial sodium channel allele T594M is not associated with blood pressure or
      blood pressure response to amiloride.
AB  - The T594M allele of the epithelial sodium channel beta-subunit has been proposed
      as a gain-of-function mutation leading to salt-sensitive hypertension in blacks
      that is particularly responsive to the specific sodium channel antagonist
      amiloride. However, the positive associations derive from small convenience
      samples, and the amiloride challenge study lacked a control group. We determined
      whether the T594M allele was associated with hypertension and blood pressure (BP)
      response to amiloride in 2 well-characterized random population samples including
      3137 Dallas County subjects and 1666 Jamaican blacks. In multivariate models, the
      T594M allele was not predictive of systolic BP (adjusted odds ratio for
      hypertension 1.1; 95% confidence interval, 0.7 to 1.8). Amiloride treatment did
      not lower the BP of 6 T594M heterozygotes significantly more than in 22 control
      subjects (P=0.8). We conclude that the T594M allele does not contribute
      significantly to BP in blacks and does not predict a significantly superior
      response to amiloride therapy.

PMID- 16432045
TI  - Therapeutic inertia is an impediment to achieving the Healthy People 2010 blood
      pressure control goals.
AB  - Therapeutic inertia (TI), defined as the providers' failure to increase therapy
      when treatment goals are unmet, contributes to the high prevalence of
      uncontrolled hypertension (> or =140/90 mm Hg), but the quantitative impact is
      unknown. To address this gap, a retrospective cohort study was conducted on 7253
      hypertensives that had > or =4 visits and > or =1 elevated blood pressure (BP) in
      2003. A 1-year TI score was calculated for each patient as the difference between
      expected and observed medication change rates with higher scores reflecting
      greater TI. Antihypertensive therapy was increased on 13.1% of visits with
      uncontrolled BP. Systolic BP decreased in patients in the lowest quintile of the
      TI score but increased in those in the highest quintile (-6.8+/-0.5 versus +1.8+/
      0.6 mm Hg; P<0.001). Individuals in the lowest TI quintile were &33 times more
      likely to have their BP controlled at the last visit than those in highest
      quintile (odds ratio, 32.7; 95% CI, 25.1 to 42.6; P<0.0001). By multivariable
      analysis, TI accounted for &19% of the variance in BP control. If TI scores were
      decreased &50%, that is, increasing medication dosages on &30% of visits, BP
      control would increase from the observed 45.1% to a projected 65.9% in 1 year.
      This study confirms the high rate of TI in uncontrolled hypertensive subjects. TI
      has a major impact on BP control in hypertensive subjects receiving regular care.
      Reducing TI is critical in attaining the Healthy People 2010 goal of controlling
      hypertension in 50% of all patients.

PMID- 16432046
TI  - Surrogate measures of arterial stiffness: do they have additive predictive value
      or are they only surrogates of a surrogate?

PMID- 16432047
TI  - Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in
      the Dublin Outcome Study.
AB  - We hypothesized that the dynamic relation between diastolic and systolic blood
      pressure over 24 hours provides a measure of arterial stiffness and might,
      therefore, predict cardiovascular mortality over and above pulse pressure. At
      baseline, while not on antihypertensive medication, 11 291 patients (mean age,
      54.6 years; 5965 women) underwent ambulatory blood pressure monitoring. Using all
      of the blood pressure readings, we plotted diastolic against systolic blood
      pressure from each individual and calculated the regression slope. The ambulatory
      arterial stiffness index (AASI) was defined as 1 minus this regression slope.
      Over a median follow-up of 5.3 years, 566 cardiovascular deaths occurred,
      including 151 from stroke and 358 from cardiac disorders. Before and after
      adjustment for other cardiovascular risk factors, AASI and pulse pressure
      significantly predicted total cardiovascular mortality. AASI was a stronger
      predictor than pulse pressure for stroke (mutually adjusted relative hazard
      ratios for 1 SD increase, 1.21 versus 1.04; P=0.02 versus 0.66) with the opposite
      trend for cardiac mortality (relative hazard ratios, 1.03 versus 1.21; P=0.63
      versus 0.002). In subjects with normal daytime ambulatory blood pressure
      (<135/<85 mm Hg), AASI was more predictive than pulse pressure of cardiovascular
      mortality (1.26 versus 0.96; P=0.04 versus 0.70) and of stroke mortality (1.81
      versus 1.12; P=0.007 versus 0.58), whereas neither independently predicted
      cardiac mortality (1.11 versus 0.89; P=0.47 versus 0.40). AASI is a novel measure
      of arterial stiffness, which can be readily determined from ambulatory blood
      pressure recordings and which independently predicts cardiovascular mortality,
      even in normotensive subjects.

PMID- 16432048
TI  - Ambulatory arterial stiffness index derived from 24-hour ambulatory blood
      pressure monitoring.
AB  - We hypothesized that 1 minus the slope of diastolic on systolic pressure during
      24-hour ambulatory monitoring (ambulatory arterial stiffness index [AASI]) might
      reflect arterial stiffness. We compared AASI with established measures of
      arterial stiffness and studied its distribution in Chinese and European
      populations. We used 90207 SpaceLabs monitors and the SphygmoCor device to
      measure AASI, central and peripheral pulse pressures, the central (CAIx) and
      peripheral (PAIx) systolic augmentation indexes, and aortic pulse wave velocity.
      In 166 volunteers, the correlation coefficient between AASI and pulse wave
      velocity was 0.51 (P<0.0001). In 348 randomly recruited Chinese subjects, AASI
      correlated (P<0.0001) with CAIx (r=0.48), PAIx (r=0.50), and central pulse
      pressure (r=0.50). AASI increased with age and mean arterial pressure but
      decreased with body height. Both before and after adjustment for arterial wave
      reflections by considering height and heart rate as covariates, AASI correlated
      more (P<0.0001) closely with CAIx and PAIx than 24-hour pulse pressure. Among
      normotensive subjects, the 95th percentile of AASI was 0.55 in Chinese and 0.57
      in 1617 Europeans enrolled in the International Database on Ambulatory Blood
      Pressure Monitoring. The upper boundary of the 95% prediction interval of AASI in
      relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In conclusion,
      AASI is a new index of arterial stiffness that can be easily measured under
      ambulatory conditions. Pending additional validation in outcome studies, normal
      values of AASI are probably <0.50 and 0.70 in young and older subjects,
      respectively.

PMID- 16432049
TI  - Hypertension and the treating physician: understanding and reducing therapeutic
      inertia.

PMID- 16432050
TI  - Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on
      ambulatory and office blood pressure.
AB  - Low-dose thiazide-type diuretics are recommended as initial therapy for most
      hypertensive patients. Chlorthalidone has significantly reduced stroke and
      cardiovascular end points in several landmark trials; however,
      hydrochlorothiazide remains favored in practice. Most clinicians assume that the
      drugs are interchangeable, but their antihypertensive effects at lower doses have
      not been directly compared. We conducted a randomized, single-blinded, 8-week
      active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force
      titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50
      mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory
      blood pressure (BP) monitoring, was assessed at baseline and week 8, along with
      standard office BP readings every 2 weeks. Thirty patients completed the first
      active treatment period, whereas 24 patients completed both. An order-drug-time
      interaction was observed with chlorthalidone; therefore, data from only the first
      active treatment period was considered. Week 8 ambulatory BPs indicated a greater
      reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared
      with hydrochlorothiazide 50 mg/day (24-hour mean = -12.4+/-1.8 mm Hg versus 
      7.4+/-1.7 mm Hg; P=0.054; nighttime mean = -13.5+/-1.9 mm Hg versus -6.4+/-1.8 mm
      Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone
      12.5 mg/day versus hydrochlorothiazide 25 mg/day (-15.7+/-2.2 mm Hg versus -4.5+/
      2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (
      17.1+/-3.7 versus -10.8+/-3.5; P=0.84). Within recommended doses, chlorthalidone
      is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced
      by 24-hour ambulatory BPs. These differences were not apparent with office BP
      measurements.

PMID- 16432051
TI  - Growth factor receptor transactivation in mediating end organ damage by
      angiotensin II.

PMID- 16432052
TI  - Imatinib attenuates end-organ damage in hypertensive homozygous TGR(mRen2)27
      rats.
AB  - Imatinib specifically inhibits receptor tyrosine kinase signaling and is
      clinically used to treat leukemia. Receptor tyrosine kinases not only mediate
      tumor growth but also initiate adverse signaling in heart failure. We
      investigated whether imatinib, by inhibiting the platelet-derived growth factor
      receptor-beta (PDGFRbeta), prevents cardiac and renal damage in TGR(mRen2)27
      (Ren2) rats. Eight-week-old male homozygous Ren2 and Sprague Dawley rats were
      treated either with imatinib (30 mg/kg; STI-571) or placebo for 8 weeks (Ren2
      n=12 for each group; Sprague Dawley n=6 for each group). Imatinib did not affect
      blood pressure or left ventricular (LV) hypertrophy in both groups. Imatinib
      attenuated the decline in fractional shortening (imatinib versus Ren2 placebo
      45+/-4.5% versus 32+/-3%; n=7-11; P<0.05) and in diastolic function in Ren2 rats
      (baseline diastolic dP/dt corrected for systolic blood pressure Ren2 imatinib
      versus Ren2 placebo 38.6+/-0.67 versus 35.3+/-0.41 [1 . s(-1)]; n=7-11; P<0.05).
      This was associated with decreased cardiac fibrosis and decreased activation of
      PDGFRbeta and extracellular signal-regulated kinase 1/2. Renal microvascular
      hypertrophy and perivascular fibrosis in Ren2 rats were significantly decreased
      by imatinib. In vitro, imatinib blocked angiotensin II-induced activation of the
      PDGFRbeta and significantly decreased fibroblast proliferation and collagen
      production. In conclusion, imatinib did not affect LV hypertrophy but attenuated
      the decline in cardiac function and reduced renal microvascular damage associated
      with reduced activation of the PDGFRbeta. The simultaneous improvement in both
      heart and kidneys suggests that inhibition of the PDGFRbeta has broad protective
      effects that may provide novel avenues for a blood pressure-independent
      protection against end-organ damage.

PMID- 16432053
TI  - Effect of salt on isoprostanes in salt-sensitive essential hypertension.
AB  - The controversy over beneficial versus harmful effects of salt on cardiovascular
      outcomes may be caused by different effects of salt on intermediate phenotypes of
      hypertension not characterized in epidemiological studies. Hence, we investigated
      acute effects of salt on oxidative stress in hypertensive subjects classified as
      salt sensitive (SS, n=14) or salt resistant (SR, n=13) by an inpatient protocol
      of salt loading (460 mmol NaCl) and salt depletion (10 mmol NaCl and furosemide).
      Oxidative stress was assessed by measuring the plasma isoprostane 8-iso
      PGF2alpha. SS had lower plasma renin activity, higher aldosterone/renin ratios,
      and exaggerated endothelin and catecholamine responses to salt depletion compared
      with SR. Baseline lipid-bound isoprostanes (749+/-70 pmol/L) were 83% of the
      total and were slightly but not significantly higher in SS than SR. Baseline free
      isoprostanes did not differ between groups. After salt loading, lipid-bound
      isoprostanes were higher in SS (945+/-106) than SR (579+/-57; P<0.01). Salt
      depletion significantly decreased them in SS (-174+/-84) and increased them in SR
      (+129+/-58), equalizing their levels (771+/-61 versus 708+/-91; P value not
      significant). Free isoprostanes were decreased by salt depletion only if data in
      all of the patients were analyzed together. Total isoprostanes followed the
      pattern of the lipid-bound fraction. Correlations between salt depletion-induced
      changes in lipid-bound isoprostanes, plasma renin activity (r=0.45; P<0.02), and
      aldosterone/renin ratios (r=-0.41; P<0.04) suggested that the more SS the
      patient, the greater the reduction of oxidative stress by salt depletion. Our
      research is the first to show that salt affects oxidative stress acutely in
      humans, particularly in SS hypertension, which may explain the controversial
      results of epidemiological studies on salt and morbidity and may have
      implications for therapy.

PMID- 16432054
TI  - Endogenous NO regulates plasminogen activator inhibitor-1 during angiotensin
      converting enzyme inhibition.
AB  - To test the hypothesis that NO contributes to effects of angiotensin-converting
      enzyme inhibitors on fibrinolysis, fibrinolytic balance was assessed in 17 normal
      subjects during placebo and after randomized, double-blind 4-week treatment with
      the NO precursor L-arginine (3 g TID), ramipril (10 mg QD), or L
      arginine+ramipril. Neither L-arginine nor ramipril alone affected basal
      plasminogen activator inhibitor-1 or tissue-type plasminogen activator (t-PA)
      antigen in these salt-replete subjects in whom plasma renin activity was
      suppressed (mean+/-SD 0.7+/-0.5 ng angiotensin I/mL per hour). In contrast, L
      arginine+ramipril reduced morning plasminogen activator inhibitor-1 antigen
      (10.8+/-9.5 ng/mL) and the molar ratio of plasminogen activator inhibitor-1:t-PA
      (2.3+/-1.6) compared with placebo (13.5+/-10.8 ng/mL, P=0.006; ratio 2.9+/-2.1,
      P=0.015) or ramipril alone (15.2+/-13.2 ng/mL, P=0.009; ratio 3.7+/-3.3,
      P=0.005). L-arginine and ramipril synergistically increased d-dimers (23.1+/
      31.5, 29.7+/-50.0, 35.1+/-50.0, and 57.1+/-144.8 ng/mL during placebo, L
      arginine, ramipril, and L-arginine+ramipril, respectively; P<0.05 for L
      arginine+ramipril versus any other group). During ramipril, the NO synthase
      inhibitor L-NG-nitro-arginine-methyl-ester (2 mg/kg) significantly increased
      plasminogen activator inhibitor-antigen after 2 hours (from 9.4+/-8.6 ng/mL
      during vehicle to 13.5+/-11.0 ng/mL during L-NG-nitro-arginine-methyl-ester;
      P=0.020), consistent with an effect on expression but rapidly increased t-PA
      activity (from 0.4+/-0.3 to 0.5+/-0.4 IU/mL; P=0.031), consistent with an effect
      on release. Both effects of L-NG-nitro-arginine-methyl-ester were reversed by L
      arginine. During angiotensin-converting enzyme inhibition, endogenous NO
      decreases plasminogen activator inhibitor-1 antigen and improves fibrinolytic
      balance in normotensive salt-replete subjects.

PMID- 16432055
TI  - Massive pulmonary embolism.
AB  - BACKGROUND: Acute massive pulmonary embolism (PE) carries an exceptionally high
      mortality rate. We explored how often adjunctive therapies, particularly
      thrombolysis and inferior vena caval (IVC) filter placement, were performed and
      how these therapies affected the clinical outcome of patients with massive PE.
      METHODS AND RESULTS: Among 2392 patients with acute PE and known systolic
      arterial blood pressure at presentation, from the International Cooperative
      Pulmonary Embolism Registry (ICOPER), 108 (4.5%) had massive PE, defined as a
      systolic arterial pressure <90 mm Hg, and 2284 (95.5%) had non-massive PE with a
      systolic arterial pressure > or =90 mm Hg. PE was first diagnosed at autopsy in
      16 patients (15%) with massive PE and in 29 patients (1%) with non-massive PE
      (P<0.001). The 90-day mortality rates were 52.4% (95% CI, 43.3% to 62.1%) and
      14.7% (95% CI, 13.3% to 16.2%), respectively. In-hospital bleeding complications
      occurred in 17.6% versus 9.7% and recurrent PE within 90 days in 12.6% and 7.6%,
      respectively (P<0.001). In patients with massive PE, thrombolysis, surgical
      embolectomy, or catheter embolectomy were withheld in 73 (68%). Thrombolysis was
      performed in 33 patients, surgical embolectomy in 3, and catheter embolectomy in
      1. Thrombolytic therapy did not reduce 90-day mortality (thrombolysis, 46.3%; 95%
      CI, 31.0% to 64.8%; no thrombolysis, 55.1%; 95% CI, 44.3% to 66.7%; hazard ratio,
      0.79; 95% CI, 0.44 to 1.43). Recurrent PE rates at 90 days were similar in
      patients with and without thrombolytic therapy (12% for both; P=0.99). None of
      the 11 patients who received an IVC filter developed recurrent PE within 90 days,
      and 10 (90.9%) survived at least 90 days. IVC filters were associated with a
      reduction in 90-day mortality (hazard ratio, 0.12; 95% CI, 0.02 to 0.85).
      CONCLUSIONS: In ICOPER, two thirds of the patients with massive PE did not
      receive thrombolysis or embolectomy. Counterintuitively, thrombolysis did not
      reduce mortality or recurrent PE at 90 days. The observed reduction in mortality
      from IVC filters requires further investigation.

PMID- 16432056
TI  - Predictors of ischemic stroke in the territory of a symptomatic intracranial
      arterial stenosis.
AB  - BACKGROUND: Antithrombotic therapy for intracranial arterial stenosis was
      recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial
      Disease (WASID) trial. A prespecified aim of WASID was to identify patients at
      highest risk for stroke in the territory of the stenotic artery who would be the
      target group for a subsequent trial comparing intracranial stenting with medical
      therapy. METHODS AND RESULTS: WASID was a randomized, double-blinded, multicenter
      trial involving 569 patients with transient ischemic attack or ischemic stroke
      due to 50% to 99% stenosis of a major intracranial artery. Median time from
      qualifying event to randomization was 17 days, and mean follow-up was 1.8 years.
      Multivariable Cox proportional hazards models were used to identify factors
      associated with subsequent ischemic stroke in the territory of the stenotic
      artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of
      these strokes were in the territory of the stenotic artery. Risk of stroke in the
      territory of the stenotic artery was highest with severe stenosis > or =70%
      (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in
      patients enrolled early (< or =17 days) after the qualifying event (hazard ratio
      1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at
      increased risk, although this was of borderline significance (hazard ratio 1.59;
      95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of
      qualifying event, and prior use of antithrombotic medications were not associated
      with increased risk. CONCLUSIONS: Among patients with symptomatic intracranial
      stenosis, the risk of subsequent stroke in the territory of the stenotic artery
      is greatest with stenosis > or =70%, after recent symptoms, and in women.

PMID- 16432058
TI  - Images in cardiovascular medicine. Not so mural thrombus.

PMID- 16432057
TI  - Cardiac metallothionein induction plays the major role in the prevention of
      diabetic cardiomyopathy by zinc supplementation.
AB  - BACKGROUND: Our previous studies showed that transgenic mice that overexpress
      cardiac-specific metallothionein (MT) are highly resistant to diabetes-induced
      cardiomyopathy. Zinc is the major metal that binds to MT under physiological
      conditions and is a potent inducer of MT. The present study therefore explored
      whether zinc supplementation can protect against diabetic cardiomyopathy through
      cardiac MT induction. METHODS AND RESULTS: Diabetes was induced in mice (C57BL/6J
      strain) by a single injection of streptozotocin. Half were supplemented
      intraperitoneally with zinc sulfate (5 mg/kg) every other day for 3 months. After
      zinc supplementation, mice were maintained for 3 more months and then examined
      for cardiomyopathy by functional and morphological analysis. Significant
      increases in cardiac morphological impairment, fibrosis, and dysfunction were
      observed in diabetic mice but not in diabetic mice supplemented with zinc. Zinc
      supplementation also induced a significant increase in cardiac MT expression. The
      role of MT in cardiac protection by zinc supplementation was examined in cultured
      cardiac cells that were directly exposed to high levels of glucose (HG) and free
      fatty acid (FFA) (palmitate), treatment that mimics diabetic conditions. Cell
      survival rate was significantly decreased for cells exposed to HG/FFA but did not
      change for cells exposed to HG/FFA and pretreated with zinc or low-dose cadmium,
      each of which induces significant MT synthesis. When MT expression was silenced
      with the use of MT small-interfering RNA, the preventive effect of pretreatment
      with zinc or low-dose cadmium was abolished. CONCLUSIONS: These results suggest
      that the prevention of diabetic cardiomyopathy by zinc supplementation is
      predominantly mediated by an increase in cardiac MT.

PMID- 16432059
TI  - Images in cardiovascular medicine. Cardiomyopathy resulting from primary
      hyperoxaluria type II.

PMID- 16432060
TI  - Images in cardiovascular medicine. Role of inflammation in atherosclerosis:
      immunohistochemical and electron microscopic images of a coronary endarterectomy
      specimen.

PMID- 16432061
TI  - Letter regarding article by Sanders et al, "spectral analysis identifies sites of
      high-frequency activity maintaining atrial fibrillation in humans".

PMID- 16432062
TI  - Historical cardiology: Dr. Adam Hammer.

PMID- 16432063
TI  - Promoting arrhythmia susceptibility.

PMID- 16432064
TI  - Rising rates of cardiac procedures in the United States and Canada: too much of a
      good thing?

PMID- 16432065
TI  - Coronary artery calcium: should we rely on this surrogate marker?

PMID- 16432066
TI  - Potassium channel subunit remodeling in rabbits exposed to long-term bradycardia
      or tachycardia: discrete arrhythmogenic consequences related to differential
      delayed-rectifier changes.
AB  - BACKGROUND: Sustained heart rate abnormalities produce electrical remodeling and
      susceptibility to arrhythmia. Uncontrolled tachycardia produces heart failure and
      ventricular tachyarrhythmia susceptibility, whereas bradycardia promotes
      spontaneous torsade de pointes (TdP). This study compared arrhythmic phenotypes
      and molecular electrophysiological remodeling produced by tachycardia versus
      bradycardia in rabbits. METHODS AND RESULTS: We evaluated mRNA and protein
      expression of subunits underlying rapid (IKr) and slow (IKs) delayed-rectifier
      and transient-outward K+ currents in ventricular tissues from sinus rhythm
      control rabbits and rabbits with AV block submitted to 3-week ventricular pacing
      either at 60 to 90 bpm (bradypaced) or at 350 to 370 bpm (tachypaced). QT
      intervals at matched ventricular pacing rates were longer in bradypaced than
      tachypaced rabbits (eg, by approximately 50% at 60 bpm; P<0.01). KvLQT1 and minK
      mRNA and protein levels were downregulated in both bradypaced and tachypaced
      rabbits, whereas ERG was significantly downregulated in bradypaced rabbits only.
      Kv4.3 and Kv1.4 were downregulated by tachypacing only. Patch-clamp experiments
      showed that IKs was reduced in both but IKr was decreased in bradypaced rabbits
      only. Continuous monitoring revealed spontaneous TdP in 75% of bradypaced but
      only isolated ventricular ectopy in tachypaced rabbits. Administration of
      dofetilide (0.02 mg/kg) to mimic IKr downregulation produced ultimately lethal
      TdP in all tachypaced rabbits. CONCLUSIONS: Sustained tachycardia and bradycardia
      downregulate IKs subunits, but bradycardia also suppresses ERG/IKr, causing
      prominent repolarization delays and spontaneous TdP. Susceptibility of
      tachycardia/heart failure rabbits to malignant tachyarrhythmias is induced by
      exposure to IKr blockers. These results point to a crucial role for delayed
      rectifier subunit remodeling in TdP susceptibility associated with rate-related
      cardiac remodeling.

PMID- 16432067
TI  - Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking
      deficient) mechanism.
AB  - BACKGROUND: The KCNH2 or human ether-a-go-go related gene (hERG) encodes the
      Kv11.1 alpha-subunit of the rapidly activating delayed rectifier K+ current (IKr)
      in the heart. Type 2 congenital long-QT syndrome (LQT2) results from KCNH2
      mutations that cause loss of Kv11.1 channel function. Several mechanisms have
      been identified, including disruption of Kv11.1 channel synthesis (class 1),
      protein trafficking (class 2), gating (class 3), or permeation (class 4). For a
      few class 2 LQT2-Kv11.1 channels, it is possible to increase surface membrane
      expression of Kv11.1 current (IKv11.1). We tested the hypotheses that (1) most
      LQT2 missense mutations generate trafficking-deficient Kv11.1 channels, and (2)
      their trafficking-deficient phenotype can be corrected. METHODS AND RESULTS: Wild
      type (WT)-Kv11.1 channels and 34 missense LQT2-Kv11.1 channels were expressed in
      HEK293 cells. With Western blot analyses, 28 LQT2-Kv11.1 channels had a
      trafficking-deficient (class 2) phenotype. For the majority of these mutations,
      the class 2 phenotype could be corrected when cells were incubated for 24 hours
      at reduced temperature (27 degrees C) or in the drugs E4031 or thapsigargin. Four
      of the 6 LQT2-Kv11.1 channels that had a wild-type-like trafficking phenotype did
      not cause loss of Kv11.1 function, which suggests that these channels are
      uncommon sequence variants. CONCLUSIONS: This is the first study to identify a
      dominant mechanism, class 2, for the loss of Kv11.1 channel function in LQT2 and
      to report that the class 2 phenotype for many of these mutant channels can be
      corrected. This suggests that if therapeutic strategies to correct protein
      trafficking abnormalities can be developed, it may offer clinical benefits for
      LQT2 patients.

PMID- 16432068
TI  - Temporal trends in the utilization of diagnostic testing and treatments for
      cardiovascular disease in the United States, 1993-2001.
AB  - BACKGROUND: Rates of invasive testing and treatment for coronary artery disease
      have increased over time. Less is known about trends in the utilization of
      noninvasive cardiac testing for coronary artery disease. The objective of this
      study was 2-fold: to explore temporal trends in the utilization of noninvasive
      and invasive cardiac services in relation to changes in the prevalence of cardiac
      disease, and to examine whether temporal increases have been targeted to
      potentially underserved populations. METHODS AND RESULTS: We performed an annual
      cross-sectional population-based study of Medicare patients from 1993 to 2001. We
      identified stress testing, cardiac catheterization, and revascularization
      procedures, as well as hospitalizations for acute myocardial infarction, during
      each year and calculated population-based rates for each using the total fee-for
      service Medicare population as the denominator and adjusting for age, gender, and
      race. We observed marked growth in the utilization rates of cardiac services over
      time, with relative rates nearly doubling for most services. Acute myocardial
      infarction hospitalization rates have remained stable over the study period.
      Although rates of all procedures except coronary artery bypass increased in all
      subgroups, differences in rates of cardiac testing and treatment between nonblack
      men and other subgroups persisted over time. CONCLUSIONS: Temporal increases in
      the use of noninvasive and invasive cardiac services are not explained by changes
      in disease prevalence and have not succeeded in narrowing preexisting treatment
      differences by gender and race. Such increases, although conferring benefit for
      some, may expose others to risk and cost without benefit.

PMID- 16432069
TI  - Proliferation of cardiac technology in Canada: a challenge to the sustainability
      of Medicare.
AB  - BACKGROUND: Critics remain skeptical about the long-term sustainability of
      Medicare in Canada because of the proliferation of health technology and
      escalating expenditures. The objective of this study was to examine the temporal
      trends in the utilization and costs of cardiovascular technologies for the
      evaluation and/or management of patients with ischemic heart disease in Canada.
      METHODS AND RESULTS: This repeated cross-sectional population-based study of
      Ontario residents examined the temporal trends in the utilization and costs
      associated with echocardiography, stress (imaging and nonimaging) testing,
      coronary angiography, percutaneous coronary intervention (PCI), and bypass
      surgery between 1992 and 2001. Annual costs increased by nearly 2-fold over the
      10-year study period and cumulatively accounted for more than $2.8 billion
      (Canadian) in expenditures. The proliferation in use of cardiac
      testing/interventions over time outstripped both demographic shifts and changes
      in the prevalence of coronary artery disease. Annual increases were widespread
      for all procedures (P<0.001) and ranged from 2% per year for nonimaging stress
      tests to 12% per year for PCI, after adjustment for age and sex. Generally,
      utilization rates were higher among the elderly, males, and those of low
      socioeconomic status. With few exceptions, annual increases in the utilization
      rates of cardiac tests and procedures were disproportionately higher among the
      elderly and women, but they were similar across socioeconomic subgroups.
      Increases in utilization appeared to reflect referrals toward higher-risk
      populations. CONCLUSIONS: Although definitive conclusions about the
      appropriateness of temporal patterns cannot be ascertained, the proliferation of
      cardiac testing challenges the sustainability of Medicare in Canada, especially
      given uncertainty as to whether the accompanying incremental rise in total
      expenditures translates into significant outcome benefits in the population.

PMID- 16432070
TI  - Mortality and cardiovascular risk across the ankle-arm index spectrum: results
      from the Cardiovascular Health Study.
AB  - BACKGROUND: A low ankle-arm index (AAI) is a strong predictor of mortality and
      cardiovascular events. A high AAI also appears to be associated with higher
      mortality risk in select populations. However, mortality and cardiovascular risk
      across the AAI spectrum have not been described in a more broadly defined
      population. METHODS AND RESULTS: We examined total and cardiovascular mortality
      and cardiovascular events across the AAI spectrum among 5748 participants in the
      Cardiovascular Health Study (CHS). The mean age of the sample population was 73+/
      6 years, and the sample included 3289 women (57%) and 883 blacks (15%). The
      median duration of follow-up was 11.1 (0.1 to 12) years for mortality and 9.6
      (0.1 to 12.1) years for cardiovascular events. There were 2311 deaths (953 of
      which were cardiovascular) and 1491 cardiovascular events during follow-up. After
      adjustment for potential confounders, AAI measurements < or =0.60 (hazard ratio
      [HR] 1.82, 95% CI 1.42 to 2.32), 0.61 to 0.7 (HR 2.08, 95% CI 1.61 to 2.69), 0.71
      to 0.8 (HR 1.80, 95% CI 1.44 to 2.26), 0.81 to 0.9 (HR 1.73 95% CI 1.43 to 2.11),
      0.91 to 1.0 (HR 1.40, 95% CI 1.20 to 1.63), and >1.40 (HR 1.57, 95% CI 1.07 to
      2.31) were associated with higher mortality risk from all causes compared with
      the referent group (AAI 1.11 to 1.20). The pattern was similar for cardiovascular
      mortality. For cardiovascular events, risk was higher at all AAI levels <1 but
      not for AAI levels >1.4 (HR 1.00, 95% CI 0.57 to 1.74). The association of a high
      AAI with mortality was stronger in men than in women and in younger than in older
      cohort members. CONCLUSIONS: In a cohort of community-dwelling elders, mortality
      risk was higher than the referent category of 1.11 to 1.2 among participants with
      AAI values above the traditional cutpoint of 0.9 (ie, 0.91 to 1.0 and >1.4), and
      the specific association of AAI with mortality varied by age and gender.

PMID- 16432071
TI  - Contrast-enhanced multidetector computed tomography viability imaging after
      myocardial infarction: characterization of myocyte death, microvascular
      obstruction, and chronic scar.
AB  - BACKGROUND: The ability to distinguish dysfunctional but viable myocardium from
      nonviable tissue has important prognostic implications after myocardial
      infarction. The purpose of this study was to validate the accuracy of contrast
      enhanced multidetector computed tomography (MDCT) for quantifying myocardial
      necrosis, microvascular obstruction, and chronic scar after occlusion/reperfusion
      myocardial infarction. METHODS AND RESULTS: Ten dogs and 7 pigs underwent balloon
      occlusion of the left anterior descending coronary artery (LAD) followed by
      reperfusion. Contrast-enhanced (Visipaque, 150 mL, 325 mg/mL) MDCT (0.5 mm x 32
      slice) was performed before occlusion and 90 minutes (canine) or 8 weeks
      (porcine) after reperfusion. MDCT images were analyzed to define infarct
      size/extent and microvascular obstruction and compared with postmortem myocardial
      staining (triphenyltetrazolium chloride) and microsphere blood flow measurements.
      Acute and chronic infarcts by MDCT were characterized by hyperenhancement,
      whereas regions of microvascular obstruction were characterized by
      hypoenhancement. MDCT infarct volume compared well with triphenyltetrazolium
      chloride staining (acute infarcts 21.1+/-7.2% versus 20.4+/-7.4%, mean difference
      0.7%; chronic infarcts 4.15+/-1.93% versus 4.92+/-2.06%, mean difference -0.76%)
      and accurately reflected morphology and the transmural extent of injury in all
      animals. Peak hyperenhancement of infarcted regions occurred approximately 5
      minutes after contrast injection. MDCT-derived regions of microvascular
      obstruction were also identified accurately in acute studies and correlated with
      reduced flow regions as measured by microsphere blood flow. CONCLUSIONS: The
      spatial extent of acute and healed myocardial infarction can be determined and
      quantified accurately with contrast-enhanced MDCT. This feature, combined with
      existing high-resolution MDCT coronary angiography, may have important
      implications for the comprehensive assessment of cardiovascular disease.

PMID- 16432072
TI  - Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults
      with repaired tetralogy of fallot and its relationship to adverse markers of
      clinical outcome.
AB  - BACKGROUND: Late morbidity and mortality remain problematic after repair of
      tetralogy of Fallot (TOF). We hypothesized that fibrosis detected by late
      gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) would be
      present in adults with repaired TOF and would be related to adverse markers of
      outcome. METHOD AND RESULTS: LGE was scored in the right and left ventricles (RV
      and LV) of 92 adult patients who had undergone TOF repair. RV LGE was seen in all
      patients at surgical sites located in the outflow tract (99%) or the site of
      ventricular septal defect patching (98%) and in the inferior RV insertion point
      (79%) and trabeculated myocardium (24%). LV LGE (53%) was located at the apex
      consistent with apical vent insertion (49%), in the inferior or lateral wall
      consistent with infarction (5%), or in other areas (8%). Patients with
      supramedian RV LGE score were older (38 versus 27 years, P<0.001) and more
      symptomatic (38% versus 8% in New York Heart Association class II or greater,
      P=0.001), had increased levels of atrial natriuretic peptide (7.3 versus 4.9
      pmol/L, P=0.041), and had a trend to higher brain natriuretic peptide (12.3
      versus 7.2 pmol/L, P=0.086), exercise intolerance (maximum VO2 24 versus 28
      mL.min(-1).kg(-1), P=0.021), RV dysfunction (RV end-systolic volume 61 versus 55
      mL/m2, P=0.018; RV ejection fraction 50% versus 56%, P=0.007), and clinical
      arrhythmia (26% versus 10%, P=0.039). Non-apical vent LV LGE also correlated with
      markers of adverse outcome. In a multivariate model, RV LGE remained a predictor
      of arrhythmia. CONCLUSIONS: RV and LV LGE were common after TOF repair and were
      related to adverse clinical markers, including ventricular dysfunction, exercise
      intolerance, and neurohormonal activation. Furthermore, RV LGE was significantly
      associated with clinical arrhythmia.

PMID- 16432073
TI  - Late stent malapposition after drug-eluting stent implantation: an intravascular
      ultrasound analysis with long-term follow-up.
AB  - BACKGROUND: Late stent malapposition (LSM) after drug-eluting stent (DES)
      implantation has not been evaluated sufficiently in real-world practice. METHODS
      AND RESULTS: We evaluated the incidence, mechanisms, predictors, and long-term
      prognosis of LSM after DES implantation in 557 patients (705 native lesions;
      sirolimus-eluting stent in 538 lesions and paclitaxel-eluting stent in 167
      lesions) in whom intravascular ultrasound was performed at index and 6-month
      follow-up. LSM occurred in 82 patients with 85 lesions (12.1% overall, 95% CI
      9.7% to 14.5%, 71 lesions (13.2%) in sirolimus-eluting stents and 14 lesions
      [8.4%] in paclitaxel-eluting stents, P=0.12]; the incidence was 25.0% (4/16)
      after directional coronary atherectomy before stenting, 27.5% (14/51) in chronic
      total occlusion lesions, and 31.8% (7/22) after primary stenting in acute
      myocardial infarction (P=0.13, P<0.001, and P=0.001, respectively, versus
      elective stenting with conventional balloon predilation, 9.7% [60/616]). There
      was an increase of external elastic membrane area (from 17.1+/-3.6 to 21.4+/-4.8
      mm2, P<0.001) that was greater than the increase in plaque area (from 9.3+/-2.5
      to 10.5+/-2.7 mm2, P<0.001). Independent predictors of LSM were total stent
      length, primary stenting in acute myocardial infarction, and chronic total
      occlusion lesions. Except for 1 death in the non-LSM group, there were no major
      adverse cardiac events in either LSM or non-LSM patients during a mean 10-month
      follow-up after detection of LSM. CONCLUSIONS: LSM occurs in 12% of cases after
      DES implantation. The predictors of LSM are total stent length, primary stenting
      in acute myocardial infarction, and chronic total occlusion lesions. LSM after
      DES implantation was not associated with any major adverse cardiac events during
      a subsequent 10-month (mean) follow-up.

PMID- 16432074
TI  - Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic
      aneurysm rupture.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) expansion is characterized by
      extracellular matrix degradation and widespread inflammation. In contrast, the
      processes that characterize AAA rupture are not well understood. The aim of this
      study was to investigate the proteolytic and cellular activity of ruptured AAA,
      focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).
      METHODS AND RESULTS: Anterior aneurysm wall biopsies were taken from 55
      nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was
      taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as
      TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of
      anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations
      between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies,
      MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies
      compared with their 12 paired anterior wall biopsies, whereas other MMPs and
      TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9
      expression was mediated by native mesenchymal cells and was independent of the
      inflammatory infiltrate. CONCLUSIONS: A localized increase in MMP-8 and -9,
      mediated by native mesenchymal cells, presents a potential pathway for collagen
      breakdown and AAA rupture.

PMID- 16432075
TI  - Physiological basis of clinically used coronary hemodynamic indices.
AB  - In deriving clinically used hemodynamic indices such as fractional flow reserve
      and coronary flow velocity reserve, simplified models of the coronary circulation
      are used. In particular, myocardial resistance is assumed to be independent of
      factors such as heart contraction and driving pressure. These simplifying
      assumptions are not always justified. In this review we focus on distensibility
      of resistance vessels, the shape of coronary pressure-flow lines, and the
      influence of collateral flow on these lines. We show that (1) the coronary system
      is intrinsically nonlinear because resistance vessels at maximal vasodilation
      change diameter with pressure and cardiac function; (2) the assumption of
      collateral flow is not needed to explain the difference between pressure-derived
      and flow-derived fractional flow reserve; and (3) collateral flow plays a role
      only at low distal pressures. We conclude that traditional hemodynamic indices
      are valuable for clinical decision making but that clinical studies of coronary
      physiology will benefit greatly from combined measurements of coronary flow or
      velocity and pressure.

PMID- 16432078
TI  - Defining molecular profiles of poor outcome in patients with invasive bladder
      cancer using oligonucleotide microarrays.
AB  - PURPOSE: Bladder cancer is a common malignancy characterized by a poor clinical
      outcome when tumors progress into invasive disease. We sought to define genetic
      signatures characteristic of aggressive clinical behavior in advanced bladder
      tumors. METHODS: Oligonucleotide arrays were utilized to analyze the transcript
      profiles of 105 bladder tumors: 33 superficial, 72 invasive lesions, and 52
      normal urothelium. Hierarchical clustering and supervised algorithms were used to
      classify and stratify bladder tumors on the basis of stage, node metastases, and
      overall survival. Immunohistochemical analyses on bladder cancer tissue arrays (n
      = 294 cases) served to validate associations between marker expression, staging
      and outcome. RESULTS: Hierarchical clustering classified normal urothelium,
      superficial, and invasive tumors with 82.2% accuracy, and stratified bladder
      tumors on the basis of clinical outcome. Predictive algorithms rendered an 89%
      correct rate for tumor staging using genes differentially expressed between
      superficial and invasive tumors. Accuracies of 82% and 90% were obtained for
      predicting overall survival when considering all patients with bladder cancer or
      only patients with invasive disease, respectively. A genetic profile consisting
      of 174 probes was identified in those patients with positive lymph nodes and poor
      survival. Two independent Global Test runs confirmed the robust association of
      this profile with lymph node metastases (P = 7.3(-13)) and overall survival (P =
      1.9(-14)) simultaneously. Immunohistochemical analyses on tissue arrays sustained
      the significant association of synuclein with tumor staging and clinical outcome
      (P = .002). CONCLUSION: Gene profiling provides a genomic-based classification
      scheme of diagnostic and prognostic utility for stratifying advanced bladder
      cancer. Identification of this poor outcome profile could assist in selecting
      patients who may benefit from more aggressive therapeutic intervention.

PMID- 16432077
TI  - Descriptive and prognostic value of patient-reported outcomes: the bortezomib
      experience in relapsed and refractory multiple myeloma.
AB  - PURPOSE: Bortezomib, a boronic acid dipeptide, has been recently introduced as a
      new approach to treating multiple myeloma (MM). The goal of this work was to
      evaluate the added value of patient-reported outcomes (PRO) in the interpretation
      of bortezomib clinical trial outcomes. PATIENTS AND METHODS: Two hundred two
      patients with relapsed, refractory MM were treated with bortezomib as part of the
      SUMMIT (Study of Uncontrolled Multiple Myeloma Managed with Proteasome Inhibition
      Therapy) study. Patients were administered the following four PRO measures at
      several time points: the European Organisation for Research and Treatment of
      Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and the myeloma
      specific module (QLQ-MY24), the Functional Assessment of Chronic Illness Therapy
      (FACIT) Fatigue scale, and the Functional Assessment of Cancer Therapy
      (FACT)/Gynecologic Oncology Group (GOG) Neurotoxicity (Ntx) scale. Minimal
      important difference (MID) thresholds were used to define patients as improved,
      stable, or worsened. A survival analysis was conducted to assess the predictive
      power of PRO data. RESULTS: For the total population, there was a positive change
      between baseline and best end point. Consistent with the clinical responses,
      change in PRO scores showed statistically significant differences between
      response groups with PRO improvement in patients with complete response (CR) or
      partial response (PR), mostly stable scores in patients with minor response or no
      change, and deterioration in most scores for patients with progressive disease.
      Change in scores for neuropathy-related symptoms was reasonably stable. In
      contrast, fatigue scores significantly improved for patients with CR or PR. When
      various MID thresholds were applied, the proportion of improved patients exceeded
      35% for several domains within all change group definitions. Moreover, survival
      analysis results demonstrated the additional prognostic information PRO data can
      provide to supplement clinical data. CONCLUSION: This study demonstrated the
      complementary value for PRO assessments in further interpreting clinical
      response, the impact of adverse effects, and patient prognosis in clinical
      trials.

PMID- 16432076
TI  - Standard chemotherapy compared with high-dose chemoradiotherapy for multiple
      myeloma: final results of phase III US Intergroup Trial S9321.
AB  - PURPOSE: Results of a prospective randomized trial conducted by the Intergroupe
      Francais du Myelome (IFM 90) indicated that autologous hematopoietic cell
      supported high-dose therapy (HDT) effected higher complete response rates and
      extended progression-free survival (PFS) and overall survival (OS) compared with
      standard-dose therapies (SDT) for patients with multiple myeloma (MM). PATIENTS
      AND METHODS: In 1993, three North American cooperative groups launched a
      prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m2
      plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine,
      MEL, cyclophosphamide, and prednisone regimen. Responders on both arms (> or =
      75%) were randomly assigned to interferon (IFN) or no maintenance treatment.
      RESULTS: With a median follow-up time of 76 months, no differences were observed
      in response rates between the two study arms (HDT, n = 261 patients; SDT, n = 255
      patients). Similarly, PFS and OS durations did not differ between the HDT and SDT
      arms, with 7-year estimates of PFS of 17% and 16%, respectively, and OS of 37%
      and 42%, respectively. Of 242 patients achieving at least 75% tumor reduction, no
      difference was observed in PFS or OS among the 121 patients randomly assigned to
      IFN and the 121 patients randomly assigned to no maintenance therapy. Among 157
      patients relapsing on SDT, 87 received a salvage autotransplantation; their
      median survival time of 30 months was only slightly better than the survival time
      of the remaining patients who were managed with further SDT (23 months; P = .13).
      CONCLUSION: The HDT and SDT regimens used in S9321 yielded comparable response
      rates and PFS and OS durations. IFN maintenance therapy did not benefit patients
      who achieved > or = 75% tumor reduction on either arm.

PMID- 16432079
TI  - Elevated serum B-lymphocyte stimulator levels in patients with familial
      lymphoproliferative disorders.
AB  - PURPOSE: Serum B-lymphocyte stimulator (BLyS) levels have been found to be
      elevated in a number of immune disease models. Therefore, we sought to establish
      whether BLyS levels were elevated in patients with B-cell lymphoproliferative
      disorders and to determine whether elevated BLyS levels correlated with clinical
      characteristics of the disease. PATIENTS AND METHODS: Specimens were collected
      from the peripheral blood of individuals diagnosed with B-cell chronic
      lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen
      at the same institution (n = 41). Serum BLyS levels were determined by enzyme
      linked immunosorbent assay, and sequencing of the BLyS promoter was performed by
      conventional methods and confirmed by restriction fragment length polymorphism
      analysis. RESULTS: We found that elevated BLyS levels were more common in
      patients with familial B-CLL than individuals with sporadic B-CLL or normal
      controls. Because of this association, we sequenced the BLyS promoter in patients
      with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We
      found that the wild-type sequence was significantly underrepresented in patients
      with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P =
      .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under
      control of the BLyS promoter containing either a C or a T at position -871, we
      found that the reporter construct containing a T at -871 had a 2.6-fold increase
      in activity (P = .004). CONCLUSION: Our data suggest serum BLyS levels are
      elevated in patients with familial B-CLL and that elevated BLyS levels correlate
      with the presence of a T at -871 in the BLyS promoter.

PMID- 16432080
TI  - Diagnosis and management of pulmonary embolism: are we moving toward an outcome
      standard?

PMID- 16432081
TI  - Relief of suffering is the business of every discipline.

PMID- 16432082
TI  - Medication-attributed adverse effects in placebo groups: implications for
      assessment of adverse effects.
AB  - Medication-attributed adverse effects are a frequent reason for poor compliance
      in practice and in clinical studies and are also common in patients receiving
      placebo. The occurrence of adverse effects in placebo groups can clarify the
      assessment of adverse event reporting. We analyzed data from randomized, placebo
      controlled trials of statin drugs published since 1992 with sample sizes larger
      than 100 subjects. Reports of adverse effects and discontinuation rates in
      placebo groups were evaluated. We compared data on adverse effect profiles in
      placebo groups between trials and with expected rates from population-based
      studies. We also sought to determine the range of adverse effect ascertainment
      methods used in different studies. Methods of ascertainment of adverse events
      varied widely across studies. Overall, 4% to 26% of patients in the control
      groups of large trials of statin drugs discontinued placebo use because of
      perceived adverse effects. The symptom rate in placebo groups varied
      substantially across trials (up to a ratio of 13:1 for possibly drug-related
      symptoms, eg, headache, 0.2%-2.7%, or abdominal pain, 0.9%-3.9%) and were often
      markedly lower than those found in the general population (eg, fatigue, 1.9%
      3.4%) in trials of statin drugs vs 17.7% in the general population. In
      conclusion, the widely varying rates of adverse effects reported by patients
      taking placebo and the high prevalence of such symptoms in the general population
      should be considered by both trialists and clinicians. In addition, variability
      of adverse effect ascertainment is considerable and suggests the need for better
      standardization in research.

PMID- 16432083
TI  - Acetylcysteine in the prevention of contrast-induced nephropathy: a case study of
      the pitfalls in the evolution of evidence.
AB  - During the past 5 years, 19 randomized controlled trials, 4 prospective
      nonrandomized studies, and 11 meta-analyses that explored the role of
      acetylcysteine for prevention of contrast-induced nephropathy have been
      published. Herein, we summarize this literature and demonstrate that these 34
      empirical studies have not yet conclusively resolved this research question. We
      use the evidence on acetylcysteine as a case study of how research evidence
      accumulates and consider whether an alternative approach to investigating the
      question of acetylcysteine's efficacy could have resulted in a more definitive
      conclusion. We consider the broader lessons learned from this acetylcysteine case
      study for the medical and research communities and propose specific steps that
      could be taken to improve the future coordination of research activity to
      ultimately yield more meaningful and definitive evidence on important clinical
      questions.

PMID- 16432084
TI  - A prediction rule to identify low-risk patients with pulmonary embolism.
AB  - BACKGROUND: A simple prognostic model could help identify patients with pulmonary
      embolism who are at low risk of death and are candidates for outpatient
      treatment. METHODS: We randomly allocated 15,531 retrospectively identified
      inpatients who had a discharge diagnosis of pulmonary embolism from 186
      Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples.
      We derived our rule to predict 30-day mortality using classification tree
      analysis and patient data routinely available at initial examination as potential
      predictor variables. We used data from a European prospective study to externally
      validate the rule among 221 inpatients with pulmonary embolism. We determined
      mortality and nonfatal adverse medical outcomes across derivation and validation
      samples. RESULTS: Our final model consisted of 10 patient factors (age > or = 70
      years; history of cancer, heart failure, chronic lung disease, chronic renal
      disease, and cerebrovascular disease; and clinical variables of pulse rate > or =
      110 beats/min, systolic blood pressure < 100 mm Hg, altered mental status, and
      arterial oxygen saturation < 90%). Patients with none of these factors were
      defined as low risk. The 30-day mortality rates for low-risk patients were 0.6%,
      1.5%, and 0% in the derivation, internal validation, and external validation
      samples, respectively. The rates of nonfatal adverse medical outcomes were less
      than 1% among low-risk patients across all study samples. CONCLUSIONS: This
      simple prediction rule accurately identifies patients with pulmonary embolism who
      are at low risk of short-term mortality and other adverse medical outcomes.
      Prospective validation of this rule is important before its implementation as a
      decision aid for outpatient treatment.

PMID- 16432085
TI  - Value of D-dimer testing for the exclusion of pulmonary embolism in patients with
      previous venous thromboembolism.
AB  - BACKGROUND: D-dimer levels remain elevated in many patients after completion of a
      6-month anticoagulant drug course for a first episode of venous thromboembolism
      (VTE), which may limit the clinical usefulness of D-dimer testing for ruling out
      a possible recurrence. METHODS: We assessed the safety and usefulness of D-dimer
      testing in patients with suspected pulmonary embolism (PE) who had experienced a
      previous VTE. We analyzed data from 2 outcome studies that enrolled 1721
      consecutive emergency department patients with clinically suspected PE.
      Information on the existence of a previous episode of VTE was abstracted from the
      database. All the patients underwent a sequential diagnostic workup, including an
      enzyme-linked immunosorbent assay D-dimer test and a 3-month follow-up. RESULTS:
      The proportion of confirmed PE was 24.1% (415/1719); PE was ruled out by a
      negative D-dimer test result in 32.7% (462/1411) of the patients without previous
      VTE but in only 15.9% (49/308) of the patients with previous VTE (P<.001). The 3
      month thromboembolic risk was 0% (95% confidence interval, 0.0%-7.9%) in patients
      with previous VTE and a negative D-dimer test result. The 2-fold lower chance of
      a negative D-dimer test result in patients with previous VTE was independent of
      older age, active malignancy, fever, and recent surgery. CONCLUSIONS: In patients
      with suspected PE and previous VTE, a negative D-dimer test result seems to allow
      safely ruling out a recurrent event. However, the proportion of negative results
      is lower in such patients, definitely reducing the clinical usefulness of the D
      dimer test in that subgroup.

PMID- 16432086
TI  - The bedside investigation of pulmonary embolism diagnosis study: a double-blind
      randomized controlled trial comparing combinations of 3 bedside tests vs
      ventilation-perfusion scan for the initial investigation of suspected pulmonary
      embolism.
AB  - BACKGROUND: We sought to determine whether using combinations of 3 bedside tests
      (7-variable clinical model, non-enzyme-linked immunosorbent assay D-dimer test,
      and alveolar dead-space fraction) to exclude pulmonary embolism (PE) before
      diagnostic imaging was as safe as a standard strategy of starting with
      ventilation-perfusion (V/Q) scan. METHODS: In this double-blind, randomized,
      controlled equivalency trial, patients were randomized to initial bedside tests
      or to initial V/Q scan without bedside tests. Patients assigned to the bedside
      test group had a sham V/Q scan performed if at least 2 of 3 bedside test results
      were negative; otherwise, they underwent an actual V/Q scan. Further diagnostic
      management was determined by a blinded physician after V/Q scan. The primary
      outcome measure was recurrent venous thromboembolic events during 3 months among
      patients who were not taking anticoagulant agents after the initial
      investigations were completed. RESULTS: Four hundred fifty-eight consecutive
      adults with suspected PE were eligible for the study; 398 of 399 consenting and
      randomized patients completed the study. The follow-up venous thromboembolic
      event rate was 2.4% in the bedside test group vs 3.0% in the V/Q scan group (P =
      .76). Pulmonary embolism was excluded in 34% (67/199) of the bedside test group
      patients with at least 2 negative results on 3 bedside tests vs 18% (35/199)
      excluded using only the 7-variable clinical model and the D-dimer test.
      CONCLUSION: Excluding PE with at least 2 negative results on 3 bedside tests
      safely eliminates the need for diagnostic imaging in 34% of patients with
      suspected PE.

PMID- 16432087
TI  - Association between circulating white blood cell count and cancer mortality: a
      population-based cohort study.
AB  - BACKGROUND: Inflammatory processes are implicated in the development and
      progression of cancer. However, it is not clear whether systemic markers of
      inflammation predict cancer. We examined the prospective relationship between
      circulating white blood cell (WBC) count and cancer mortality. METHODS:
      Population-based cohort study of 3189 individuals, aged 49 to 84 years and free
      of cancer at the baseline examination (January 1, 1992, to December 31, 1994), in
      the Blue Mountains region, west of Sydney, Australia. The main outcome of
      interest was all cancer mortality ascertained from vital status as of December
      31, 2001. RESULTS: Higher WBC count was found to be associated with all cancer
      mortality. In proportional hazards models adjusting for age, sex, education, body
      mass index, hematocrit level, alcohol consumption, physical inactivity, smoking,
      weekly aspirin use, diabetes mellitus or fasting hyperglycemia status, and
      fasting glucose levels, the multivariable relative risk of all cancer mortality
      comparing quartile 4 of WBC count ( > or = 7400 cells/microL) with quartile 1 (<
      or = 5300 cells/microL) was 1.73 (95% confidence interval [CI], 1.18-2.55). In
      subgroup analyses, the relative risk of cancer mortality comparing quartile 4 of
      WBC count with quartile 1 was higher among those with diabetes or fasting
      hyperglycemia (3.03 [95% CI, 1.01-9.15]) than among those with normoglycemia
      (1.68 [95% CI, 1.12-2.52]). Also, the relative risk of cancer mortality
      associated with joint exposure to quartile 4 of WBC count and aspirin nonuse was
      2.42 (95% CI, 1.46-4.01) compared with their absence. CONCLUSION: These data
      provide new epidemiological evidence of an association between circulating WBC
      count, a widely available marker of inflammation, and subsequent cancer
      mortality.

PMID- 16432088
TI  - Clinical depression and risk of out-of-hospital cardiac arrest.
AB  - BACKGROUND: The association of depression with coronary heart disease-related
      mortality has been widely recognized. This finding may partly reflect an
      association between depression and sudden death, in part because the imbalance
      between sympathetic and parasympathetic tone is altered in depressed subjects.
      We, thus, investigated whether the presence and severity of clinical depression
      was associated with a higher risk of sudden cardiac death. METHODS: We used data
      from a population-based case-control study of risk factors for incident out-of
      hospital cardiac arrest (CA) conducted among enrollees of a health maintenance
      organization in western Washington State. Cases (n = 2228) were aged 40 to 79
      years and experienced CA between January 1, 1980, and December 31, 1994. Controls
      (n = 4164) were a stratified random sample of enrollees defined by calendar year,
      age, sex, and prior heart disease. Clinical depression was defined as physician
      diagnosis of depression or use of antidepressant treatment within the year before
      the event. Referral to mental health clinics or hospitalization for depression
      defined severe depression. RESULTS: Clinically depressed patients had a higher
      odds ratio (OR) of CA (1.88; 95% confidence interval [CI], 1.59-2.23), which
      persisted after adjustment for confounders (OR, 1.43; 95% CI, 1.18-1.73). The
      association was observed in both sexes, in various age groups, and in subjects
      with prior physician-diagnosed heart disease (OR, 1.27; 95% CI, 1.01-1.60) and
      without prior physician-diagnosed heart disease (OR, 1.71; 95% CI, 1.22-2.41) (P
      = .13 for the interaction). Compared with nondepressed subjects, the risk of CA
      was increased in less severely depressed subjects (OR, 1.30; 95% CI, 1.04-1.63)
      and further increased in severely depressed subjects (OR, 1.77; 95% CI, 1.28
      2.45) (P<.001 for trend). CONCLUSION: Clinical depression may be associated with
      a higher risk of CA independently of established coronary heart disease risk
      factors.

PMID- 16432089
TI  - Prediction of coronary heart disease by erectile dysfunction in men referred for
      nuclear stress testing.
AB  - BACKGROUND: Recent evidence suggests a strong link between erectile dysfunction
      (ED) and atherosclerotic vascular disease. Stress myocardial perfusion single
      photon emission computed tomography (MPS) is a widely used noninvasive imaging
      modality that allows diagnosis of coronary heart disease and stratification of
      cardiovascular risk. We sought to determine the relationship between ED and
      coronary heart disease in men referred for MPS. METHODS: A total of 221 men
      referred for MPS were prospectively screened for ED with a validated
      questionnaire. Patient characteristics, MPS findings, and exercise results were
      correlated with ED. RESULTS: Erectile dysfunction was present in 54.8% of the
      patients. Patients with ED exhibited more severe coronary heart disease (MPS
      summed stress score >8) (43.0% vs 17.0%; P<.001) and left ventricular dysfunction
      (left ventricular ejection fraction <50%) (24.0% vs 11.0%; P=.01) than those
      without ED. Erectile dysfunction was associated with a shorter exercise time (8.0
      vs 10.1 minutes; P<.001) and lower Duke treadmill score (4.4 vs 8.4; P<.001).
      Multivariate analysis showed ED to be an independent predictor of severe coronary
      heart disease (odds ratio, 2.50; 95% confidence interval, 1.24-5.04; P = .01) and
      high-risk MPS findings (summed stress score >8, transient ischemic dilation, or
      left ventricular ejection fraction <35%) (odds ratio, 2.86; 95% confidence
      interval, 1.43-5.74; P = .003). CONCLUSIONS: Erectile dysfunction is common in
      men referred for MPS, is associated with markers of adverse cardiovascular
      prognosis, and is an independent predictor of severe coronary heart disease and
      high-risk MPS findings. These results suggest that questioning about sexual
      function may be a useful tool for stratifying risk in individuals with suspected
      coronary heart disease.

PMID- 16432090
TI  - Predictors and prevalence of erectile dysfunction in a racially diverse
      population.
AB  - BACKGROUND: To our knowledge, the burden of disease attributed to erectile
      dysfunction (ED) has not been adequately quantified across a complete spectrum of
      age and race using a global disease definition, as recommended by the National
      Institutes of Health consensus statement. To obtain a better understanding of the
      national estimates of prevalence and risk factors for ED, we analyzed data from
      the 2001-2002 National Health and Nutrition Examination Survey. METHODS: The
      National Health and Nutrition Examination Survey collects data by household
      interview. The sample design is a stratified, multistage, probability sample of
      clusters of persons representing the civilian noninstitutionalized population.
      Data include medical histories in which specific queries are made regarding
      urological symptoms (including ED). These items were selected for analysis in
      3566 men, 20 years and older. RESULTS: In men 20 years and older, ED affected
      almost 1 in 5 respondents. Hispanic men were more likely to report ED (odds ratio
      [OR], 1.89), after controlling for other factors. The prevalence of ED increased
      dramatically with advanced age; 77.5% of men 75 years and older were affected. In
      addition, there were several modifiable risk factors that were independently
      associated with ED, including diabetes mellitus (OR, 2.69), obesity (OR, 1.60),
      current smoking (OR, 1.74), and hypertension (OR, 1.56). CONCLUSIONS: The burden
      of ED on the US population is significant. Hispanic men had an elevated risk for
      ED, a finding that requires confirmation in prospective studies. Obesity,
      hypertension, smoking, and diabetes mellitus are significantly associated with ED
      risk. Mitigation of these risk factors may ameliorate the burden of ED.

PMID- 16432091
TI  - The prevalence of erectile dysfunction in the primary care setting: importance of
      risk factors for diabetes and vascular disease.
AB  - BACKGROUND: The prevalence of erectile dysfunction (ED) and associated risk
      factors has been described in many clinical settings, but there is little
      information regarding men seen by primary care physicians. We sought to identify
      independent factors associated with ED in a primary care setting. METHODS: We
      surveyed a cross-sectional sample of 3921 Canadian men, aged 40 to 88 years, seen
      by primary care physicians. Participants completed a full medical history,
      physical examination, and measurement of fasting blood glucose and lipid levels.
      We used the International Index of Erectile Function to define ED as a score of
      less than 26 on the erectile function domain. RESULTS: The overall prevalence of
      ED was 49.4%. The presence of cardiovascular disease (odds ratio [OR], 1.45; 95%
      confidence interval [CI], 1.16-1.81; P<.01) or diabetes (OR, 3.13; 95% CI, 2.35
      4.16; P<.001) increased the probability of ED after adjustment for other
      confounders. Among those individuals without cardiovascular disease or diabetes,
      the calculated 10-year Framingham coronary risk (OR, 1.03 per 1% increase; 95%
      CI, 1.02-1.05; P<.001) and fasting blood glucose levels (OR, 1.14 per 18-mg/dL [1
      mmol/L] increase; 95% CI, 1.04-1.24; P<.01) were independently associated with
      ED. Erectile dysfunction was also independently associated with undiagnosed
      hyperglycemia (OR, 1.46; 95% CI, 1.02-2.10; P = .04), impaired fasting glucose
      (OR, 1.26; 95% CI, 1.08-1.46; P = .004), and the metabolic syndrome (OR, 1.45;
      95% CI, 1.24-1.69; P<.001). CONCLUSIONS: Cardiovascular disease, diabetes, future
      coronary risk, and increasing fasting glucose levels are independently associated
      with ED. It remains to be determined if ED precedes the development of these
      conditions.

PMID- 16432092
TI  - Health-related quality of life and appropriateness of knee or hip joint
      replacement.
AB  - BACKGROUND: We studied the association between explicit appropriateness criteria
      for total hip joint replacement (THR) and total knee replacement (TKR) with
      changes in health-related quality of life of patients undergoing these
      procedures. METHODS: Prospective observational study of 1576 consecutive patients
      with diagnoses of osteoarthritis on waiting lists to undergo THR or TKR. Explicit
      appropriateness criteria using the RAND appropriateness method were applied.
      Patients completed 2 questionnaires that measured health-related quality of life,
      the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), before
      the procedure and 6 months afterward. RESULTS: Patients who were considered
      appropriate candidates for these procedures had greater improvements than those
      who were considered inappropriate candidates in all 3 WOMAC domains (pain,
      functional limitation, and stiffness; THR: 43.0, 40.6, and 40.4 vs 14.7, 19.1,
      and 15.9; TKR: 34.9, 32.5, and 30.2 vs 23.2, 18.9, and 17.1; P<.001 for all
      comparisons). Patients who underwent THR and were judged to be appropriate
      candidates had greater improvements in the physical function, role-physical,
      bodily pain, and social function domains of the SF-36 than those judged to be
      inappropriate candidates (34.4, 35.1, 33.1, and 26.6 vs 19.6, 9.2, 5.7, and 7.0;
      P = .04, P = .03, P < .001, and P < .001, respectively). Appropriate candidates
      for TKR demonstrated greater improvement in the social function domain of the SF
      36 after the procedure than those deemed inappropriate candidates (19.9 vs 7.9; P
      = .004) but not in the other domains of functional status. CONCLUSIONS: These
      results suggest a direct relationship between explicit appropriateness criteria
      and better health-related quality-of-life outcomes after THR and TKR surgery. Our
      results support the use of these criteria for clinical guidelines or evaluation
      purposes.

PMID- 16432093
TI  - Evaluating the California Hospital Initiative in Palliative Services.
AB  - BACKGROUND: Inpatient palliative care programs can improve care of patients with
      serious illness. We developed the California Hospital Initiative in Palliative
      Services (CHIPS) program to assist hospitals in establishing these programs.
      CHIPS included an introductory conference followed by 10 months of mentoring with
      telephone calls, e-mails, on-site consultation at the hospital, and a reunion
      conference. METHODS: To evaluate CHIPS and the factors associated with
      establishing inpatient palliative care programs, we conducted a cross-sectional
      telephone survey of leaders from the 38 hospitals that participated in CHIPS. We
      assessed the number of inpatient palliative care consultation services
      established by hospitals that participated in CHIPS (success) and hospital
      characteristics associated with success. RESULTS: Participants gave CHIPS high
      ratings. Six hospitals (16%) had a palliative care consultation service at
      enrollment in CHIPS and 19 hospitals (60%) established one after participation in
      CHIPS (P<.001). In bivariable comparisons, successful hospitals were more likely
      to have a hospitalist program (P = .003) or to be located in an urban setting (P
      = .03). CONCLUSIONS: CHIPS seemed to help many hospitals establish inpatient
      palliative care programs. Hospitals with hospitalists and those in an urban
      setting were more likely to succeed in developing palliative care programs.
      Future studies should focus on the quantity and quality of care provided by these
      programs.

PMID- 16432094
TI  - Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud
      disease.
AB  - BACKGROUND: Raynaud disease (RD) is a common disorder affecting 3% to 5% of the
      healthy population, and occurs in more than 90% of patients with connective
      tissue diseases. The therapeutic options remain limited, particularly in patients
      with secondary RD due to connective tissue disease. Theoretical considerations
      lead to the expectation that phosphodiesterase type 5 inhibitors may improve
      clinical symptoms and digital blood flow in patients with RD. METHODS: We
      conducted an open-label pilot study in 40 patients with RD, 33 (82%) of whom had
      secondary and 7 (18%) of whom had primary RD. Digital blood flow was measured by
      laser-Doppler flowmetry at room temperature and during the cold-exposure test
      before medical treatment, 1 hour after the initial intake, and after 2 weeks of
      continuous treatment (10 mg twice a day) with the novel phosphodiesterase type 5
      inhibitor vardenafil. Clinical symptoms were recorded by a patient questionnaire
      and summarized as the Raynaud condition score. RESULTS: Laser-Doppler flowmetry
      revealed that vardenafil improved digital blood flow in 28 (70%) patients,
      whereas 12 (30%) did not respond. In individuals responding, digital blood flow
      significantly increased by a mean +/- SEM of 21.0% +/- 4.9% and 30.0% +/- 5.7% at
      1 hour and 2 weeks of treatment at room temperature, respectively, and by 18.8%
      +/- 4.4% and 35.1% +/- 7.5% at 1 hour and 2 weeks during the cold-exposure test,
      respectively (P < .01 for all). Consistently, clinical symptoms improved in 27
      (68%) of the 40 patients, and the Raynaud condition score declined from a mean +/
      SEM of 5.05 +/- 0.38 to 3.54 +/- 0.31 (P < .001). CONCLUSION: Our data indicate
      that phosphodiesterase type 5 inhibition significantly improves peripheral blood
      flow and clinical symptoms in a large subset of patients with RD and, thus, may
      provide a novel therapeutic approach in such individuals.

PMID- 16432095
TI  - Assessing the performance of overseas tuberculosis screening programs: a study
      among US-bound immigrants in Vietnam.
AB  - BACKGROUND: Tuberculosis cases in foreign-born persons account for more than 50%
      of all tuberculosis cases in the United States. The Institute of Medicine has
      recommended enhancing overseas screening as one measure to support tuberculosis
      elimination efforts. We assessed the ability of overseas tuberculosis screening
      (chest radiograph followed by 3 acid-fast bacilli sputum smears for persons with
      abnormal chest radiographs [suggestive of active tuberculosis]) to detect
      pulmonary tuberculosis disease among US-bound immigrants with abnormal chest
      radiographs. METHODS: During October 1998 to October 1999, 14 098 US immigrant
      visa applicants were screened overseas in Vietnam. Adult applicants with abnormal
      chest radiographs were enrolled to assess screening test characteristics among
      this group using mycobacterial culture as the gold standard for pulmonary
      tuberculosis disease diagnosis. Risk factors for pulmonary tuberculosis disease
      were also evaluated. RESULTS: Among 1179 adult applicants with abnormal chest
      radiographs, 82 (7.0%) had positive acid-fast bacilli smear results, and 183
      (15.5%) had positive Mycobacterium tuberculosis culture results (pulmonary
      tuberculosis disease). The sensitivity, specificity, and positive and negative
      predictive values of serial acid-fast bacilli screening among this group were
      34.4% (63/183), 98.1% (977/996), 76.8% (63/82), and 89.1% (977/1097),
      respectively. Risk factors for pulmonary tuberculosis disease included younger
      age (18-34 years), no history of tuberculosis or treatment, reported symptoms,
      and cavitation or consolidation on chest radiograph. CONCLUSIONS: The ability of
      current overseas screening to detect tuberculosis among immigrants with abnormal
      chest radiographs is low. Improved diagnostic methods, enhanced screening
      measures, and postmigration follow-up are essential to control tuberculosis among
      immigrants and support US and global tuberculosis elimination.

PMID- 16432097
TI  - The use of proton pump inhibitors as a diagnostic test for gastroesophageal
      reflux disease.

PMID- 16432096
TI  - Risk of osteoporotic fracture in elderly patients taking warfarin: results from
      the National Registry of Atrial Fibrillation 2.
AB  - BACKGROUND: Vitamin K allows for gamma-carboxylation of glutamyl residues, a
      conversion that activates clotting factors and bone proteins. Vitamin K
      antagonists such as warfarin inhibit this process. Our goal was to quantify the
      association between warfarin and osteoporotic fractures in patients with atrial
      fibrillation. METHODS: This was a retrospective cohort study of Medicare
      beneficiaries with atrial fibrillation who were hospitalized between March 1998
      and April 1999 in all 50 US states. The study outcome was osteoporotic fractures,
      identified by an International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) code for a fracture of the hip, spine, or wrist.
      RESULTS: Compared with 7587 patients who were not prescribed warfarin, the
      adjusted odds ratio (OR) of fracture was 1.25 (95% confidence interval [CI], 1.06
      1.48) in 4461 patients prescribed long-term warfarin therapy (> or = 1 year). The
      association between osteoporotic fracture and long-term warfarin use was
      significant in men (OR, 1.63; 95% CI, 1.26-2.10) but nonsignificant in women (OR,
      1.05; 95% CI, 0.88-1.26). In 1833 patients prescribed warfarin for less than a
      year, the risk of osteoporotic fracture was not increased significantly (OR,
      1.03). Odds ratios (95% CIs) of independent predictors of osteoporotic fractures
      were as follows: increasing age, 1.63 (1.47-1.80) per decade; high fall risk,
      1.78 (1.42-2.21); hyperthyroidism, 1.77 (1.16-2.70); neuropsychiatric disease,
      1.51 (1.28-1.78); and alcoholism, 1.50 (1.01-2.24). Factors with a reduced OR
      (95% CI) included African American race, 0.30 (0.18-0.51); male sex, 0.54 (0.46
      0.62); and use of beta-adrenergic antagonists, 0.84 (0.70-1.00). CONCLUSIONS:
      Long-term use of warfarin was associated with osteoporotic fractures, at least in
      men with atrial fibrillation. Beta-adrenergic antagonists may protect against
      osteoporotic fractures.

PMID- 16432098
TI  - Heart rate variability in women.

PMID- 16432099
TI  - Noncardiac chest pain and proton pump inhibitors.

PMID- 16432100
TI  - Why the plasma TG/HDL-C concentration ratio does not predict insulin resistance
      in African Americans.

PMID- 16432101
TI  - Systemic atherosclerosis and kidney disease.

PMID- 16432102
TI  - Late entrapment of ball and cage valve in mitral position.
AB  - A 32-year-old female underwent mitral valve replacement with total chordal
      preservation (Miki's technique) using 26 mm (1M) Starr-Edward prosthesis (SEP) in
      1988. The patient was in NYHA class-I until 2001. She progressed to NYHA class
      III with paroxysmal nocturnal dyspnoea. Transthoracic echocardiogram showed
      increased prosthetic valve gradient, and cardiac catheterization confirmed the
      findings. Intraoperatively, the poppet movement in the cage was found to be
      restricted due to the preserved subvalvular apparatus entrapping the poppet
      inside the prosthetic valve cage.

PMID- 16432103
TI  - Post-pneumonectomy syndrome in an adult presenting with positional syncope.
AB  - Post-pneumonectomy syndrome is a rare late complication of pneumonectomy, which
      is due to extreme mediastinal shift and rotation into the pneumonectomy space.
      Recurrent syncope following a right pneumonectomy in a 21-year-old woman was
      treated by insertion of an expandable silicone prosthesis into the pneumonectomy
      space.

PMID- 16432104
TI  - Sternotomy reconstruction with omentum followed by large diaphragmatic hernia.
AB  - Poststernotomy mediastinitis carries significant morbidity and mortality.
      Aggressive wound debridement combined with a pedicled omental flap, with or
      without a pedicled muscle flap, has gained acceptance in the management of
      difficult sternal wound infections. Two cases of poststernotomy mediastinitis and
      sternal wound reconstruction with a pedicled omental flap were complicated by a
      large anterior diaphragmatic hernia containing the large bowel.

PMID- 16432106
TI  - A pitfall in ligation of intrahepatic shunting after Fontan type operation.
AB  - An 8-year-old boy experienced progressive cyanosis after a Fontan type operation.
      Under the guidance of intraoperative color Doppler we performed a transabdominal
      ligation of the accessory hepatic veins which drained into a common atrium.
      Reoperation was needed through a median sternotomy to eliminate residual
      shunting. Although intraoperative Doppler is useful to aid in the ligation of
      accessory veins while portal hypertension is monitored, intraoperative angiogram
      serves better to ensure the elimination of intrahepatic shunting in a
      transabdominal approach.

PMID- 16432105
TI  - A surgical case of symptomatic coronary artery-pulmonary artery fistula.
AB  - We describe a 55-year-old female patient with multiple plexiform coronary artery
      pulmonary artery fistulas, who presented with ischemic episodes accompanying an
      inversion of T wave on an electrocardiogram even though it was a small shunt
      size. The surgical procedure involved closure of the openings of the fistulas
      from inside the pulmonary trunk using cardiopulmonary bypass with additional
      ligations. Postoperative coronary angiogram revealed complete interruption of the
      coronary artery-pulmonary trunk fistulas resulting in complete resolution of the
      patient's chest symptoms.

PMID- 16432107
TI  - Spontaneous cervical emphysema and pneumomediastinum in an 18-year-old woman.
AB  - Pneumomediastinum or mediastinal emphysema is a known complication of traumatic
      injury or disease whereas spontaneous pneumomediastinum remains a rare clinical
      entity. We present the case of a young woman with a diagnosis of spontaneous
      pneumomediastinum combined with cervical emphysema without any precipitating
      factors or disease.

PMID- 16432108
TI  - The Ross operation--an evolutionary tale.

PMID- 16432109
TI  - Pulmonary sequestration and surgical treatment.
AB  - Pulmonary sequestration is nonfunctioning, abnormal pulmonary tissue existing
      inside or outside the visceral pleura. It is not connected to the
      tracheobronchial tree. In this study, the results of 8 patients, who were
      diagnosed with pulmonary sequestration and treated during hospitalization in
      Gulhane Military Medical Academy between 1996 and 2003, were reported. Sex, age,
      symptoms, diagnostic approach, operative findings, procedures and postoperative
      outcomes were reviewed. No postoperative complications were seen. In the long
      term follow-up all patients were seen to be asymptomatic. We believe surgical
      resection is mandatory in order to avoid infection and destruction of the normal
      pulmonary parenchyma even in asymptomatic cases. Furthermore, when infection
      occurs, major resection such as lobectomy may be necessary rather than
      segmentectomy or wedge resection, which involves removal of minimal pulmonary
      parenchyma.

PMID- 16432110
TI  - Cor triatriatum: operative results in 20 patients.
AB  - Cor triatriatum is an uncommon cardiac anomaly occurring in 0.1% of children with
      congenital heart disease. We reviewed our results from 20 patients presenting
      with cor triatriatum in the last 20 years (from March 1983 to August 2002). Mean
      age at repair was 20 months (1-132 months). During a mean follow-up period of 31
      months (2-156 months) there were no deaths. All patients were in sinus rhythm
      except one patient who needed pacemaker insertion one week after repair. A total
      of 14 patients were asymptomatic and 6 were in New York Heart Association Class
      I. Cor triatriatum is amenable to surgical repair with excellent results when
      diagnosed early, and when not associated with other severe cardiac anomalies.

PMID- 16432111
TI  - Low-prime system minimizes transfusions and hemodilution in coronary bypass.
AB  - Standard heart-lung machines lead to substantial hemodilution with associated
      impaired organ function and increased need for blood transfusions. The aim of
      this study was to evaluate the effect of the new PRECiSe low prime volume system
      on perioperative myocardial damage, hemodilution, and transfusions. In a case
      matched prospective study, 40 patients undergoing coronary artery bypass surgery
      using PRECiSe were compared with 40 patients on a standard heart-lung machine. In
      the PRECiSe group, the prime volume was significantly reduced, resulting in less
      hemodilution and transfusion requirements during and after extracorporeal
      circulation: only 10% of patients needed transfusions vs. 35% in the control
      group, with an average transfusion need of 0.16 vs. 1.25 units. There were no
      significant differences in perioperative cardiac-specific enzymes. The PRECiSe
      system was considered safe and effective for coronary artery bypass surgery.

PMID- 16432112
TI  - Ascending aorta or arch surgery: is previous cardiac surgery a risk factor?
AB  - Surgery on the ascending aorta +/- arch is a challenge. The risks involved in
      such operations after previous cardiac surgery were assessed in elective and
      emergency settings in a single institution. Over a 10-year period, 29 patients
      underwent replacement of the ascending aorta +/- arch following previous cardiac
      surgery. In 12 patients (41.4%), the procedure was carried out on an emergency
      basis. Thirteen had previous replacement of the ascending aorta and 16 had
      previous valve replacement with or without coronary artery bypass; 4 patients
      were undergoing a 3rd cardiac operation. Concomitant procedures included coronary
      artery bypass in 2, arch replacement in 4, and descending aortic replacement in
      one. The overall in-hospital mortality was 13.8% (4/29) vs. 12.4% (33/267) in
      primary procedures. Mortality in elective repeat surgery was 5.9% (1/17) vs. 25%
      (3/12) in emergency re-operations. The incidences of permanent stroke (3.4%) and
      renal failure (3.4%) were similar to first-time operations. Elective re-operation
      for ascending aorta +/- arch repair can be accomplished with acceptable mortality
      and morbidity. Outcomes in emergency cases carry a higher early mortality but
      still conform to contemporary expectations and are similar to emergency first
      time aortic surgery.

PMID- 16432113
TI  - Perioperative circulating blood volume and cardiac function in valve disease.
AB  - Circulating blood volume is important in managing fluid balance and cardiac
      function after surgery under cardiopulmonary bypass. Appropriate management
      differs among the valve disorders, but perioperative blood volume has not yet
      been considered. From February 2001 to March 2003, perioperative blood volume,
      fluid balance, cardiac index, and left ventricular stroke work index were
      measured in 31 patients: 10 with aortic stenosis, 9 with aortic regurgitation, 3
      with mitral stenosis, and 9 with mitral regurgitation. All immediate
      postoperative blood volume measurements were less than preoperative values, and
      gradually returned to baseline. At all time points, blood volume in patients with
      aortic or mitral regurgitation was high, whereas it was low in those with
      stenosis, especially mitral stenosis. Fluid balance was positive in all patients.
      Postoperatively, there was a positive correlation between cardiac index and blood
      volume in all groups. The left ventricular stroke work index in the mitral
      regurgitation group was significantly higher than other groups, the aortic
      stenosis group was slightly lower, the mitral stenosis and mitral regurgitation
      groups were higher than the baseline, and the aortic regurgitation group was
      essentially unchanged. Thus, it is necessary to consider blood volume
      perioperatively in different valvular diseases to manage water balance.

PMID- 16432114
TI  - Left ventricular rupture after mitral valve replacement: a report of 13 cases.
AB  - Left ventricular rupture after mitral valve replacement is a rare but lethal
      complication. Between 1995 and 2003, left ventricular rupture occurred in 13 of
      5,449 patients who underwent mitral valve replacement, with an incidence of
      0.24%. There were 4 immediate ruptures and 9 delayed ruptures. Urgent repair of
      the rupture was performed under cardiopulmonary bypass in 11 cases. All mitral
      prostheses were explanted. External repair alone was performed in one patient.
      External repair combined with internal repair was performed in 10 patients. Two
      patients died of cardiac tamponade and failure of cardiac resuscitation. Of the
      11 patients who had a re-operation, 6 died in hospital and 5 survived. The
      mortality was 61.5% (8/13). At a mean follow-up of 4 years, 2 patients were in
      New York Heart Association functional class II and 3 were in class III. Proper
      diseased valve removal, decalcification, and prosthesis selection could minimize
      the incidence of left ventricular rupture. Immediate diagnosis and urgent
      surgical intervention are crucial for successful repair.

PMID- 16432115
TI  - Relationship of tumor size to survival in patients with pT2N0 lung cancer.
AB  - Lung cancer extending beyond 3 cm in diameter without lymph node or distant
      metastasis is defined as T2. The purpose of this study was to analyze the
      prognosis based on tumor size for patients with resected T2N0M0 non-small cell
      lung cancer. The 268 patients who underwent complete resection of a lung tumor >
      3 cm in diameter were reviewed retrospectively. They were divided into 3 groups
      based on tumor size: 3-5 cm, > 5-7 cm, and > 7 cm. There were significant
      differences in the 5-year survival rates of 61.4%, 47.9%, and 21.9% in each
      group, respectively. In the two subgroups with tumor sizes 3-4 cm and > 4 cm, the
      5-year survival was 63.8% and 48.1%, respectively. Tumors > 4 cm in diameter
      indicate a poor long-term prognosis.

PMID- 16432116
TI  - Femoral artery cannulation in Stanford type A aortic dissection operations.
AB  - The aim of this study was to evaluate femoral artery cannulation in Stanford type
      A aortic dissection operations. Between March 1994 and December 2001, 88 patients
      with Stanford type A aortic dissection underwent surgery with cardiopulmonary
      bypass and perfusion through the femoral artery; 31 of them had deep-hypothermic
      circulatory arrest. False lumen perfusion was detected in 8 patients (9.1%).
      There were 4 (4.5%) cerebral events: 2 patients had diffuse cerebral injury, with
      one death; and 2 patients had hemiplegia, with one death. Six patients (8.0%) had
      delayed incision healing, with local infection in one. There was no lower
      extremity ischemia associated with femoral artery cannulation. It was concluded
      that retrograde perfusion through the femoral artery was effective for repair of
      aortic dissection, with a low risk of those cerebral events associated with a
      high mortality rate.

PMID- 16432117
TI  - Anomalous origin of left coronary artery from pulmonary artery in adults.
AB  - Various techniques have been described for management of anomalous origin of the
      left coronary artery from the pulmonary artery presenting in adults. Three
      patients, 1 male and 2 females, aged 27-37 years, underwent transpulmonary
      pericardial patch closure with concomitant left internal thoracic artery
      anastomosis to the left anterior descending artery, under standard
      cardiopulmonary bypass, thus creating a two-coronary system. One patient had
      concomitant mitral valve repair. All 3 survived the operation. Postoperative
      angiography in 2 patients revealed good antegrade flow with decreased collaterals
      in one and competitive inhibition with increased collaterals in the other. This
      procedure is considered to be the safest and simplest in this subset of patients.

PMID- 16432118
TI  - Magnetic resonance angiography in coronary artery bypass grafting.
AB  - An attempt was made to reduce the incidence of perioperative stroke by detecting
      cerebrovascular disease with preoperative head and neck magnetic resonance
      angiography and by selecting the coronary artery bypass grafting technique. This
      strategy was used in 268 patients with ischemic heart disease who had undergone
      both head and neck magnetic resonance angiography before elective coronary artery
      bypass in our hospital between May 1997 and April 2001. In patients with
      significant stenosis or obstruction detected by head and neck magnetic resonance
      angiography, the findings were evaluated and cerebral blood flow was examined
      using brain single-photon emission computed tomography. In those with a high risk
      of cerebrovascular ischemia, off-pump coronary artery bypass was performed to
      maintain cerebral blood flow. No stroke occurred during surgery, and hemodynamic
      cerebrovascular ischemia was prevented in all 268 patients. Postoperative stroke
      occurred in 3 patients (1.1%), but the incidence of perioperative stroke was
      reduced.

PMID- 16432119
TI  - Long-term results of triple-valve procedure.
AB  - Triple-valve procedures are associated with high early and late mortality. We
      reviewed our experience in 25 patients who underwent combined mitral and aortic
      valve replacement with tricuspid valve repair or replacement between 1979 and
      2004. The mean follow-up was 7.8 years (range, 10 days to 24.5 years). The mean
      age at operation was 52 years (range, 31 to 72 years). Four patients underwent
      triple-valve replacement and 21 had double-valve replacement and tricuspid
      annuloplasty. Perioperative mortality was 20% and late mortality was 24%.
      Cumulative survival, calculated taking perioperative mortality into account, was
      71% +/- 10% at 10 years and 36% +/- 15% at 15 years after surgery. Only 1 of 20
      perioperative survivors required re-operation for prosthetic valve dysfunction.
      Double-valve replacement with tricuspid annuloplasty offers satisfactory long
      term survival with freedom from thromboembolism and re-operation.

PMID- 16432120
TI  - Cardiopulmonary bypass without preoperative exchange transfusion in sicklers.
AB  - The effect of hypothermic cardiopulmonary bypass techniques on the sickling
      process was evaluated in patients with sickle cell hemoglobin. It was presumed
      that intraoperative hemolysis, as identified by hemoglobinuria, reflected
      increased sickling. Data of 43 patients with sickle cell traits and 2 with sickle
      cell disease, who were operated on under cardiopulmonary bypass and cold
      cardioplegic arrest in a tertiary center from the beginning of 1995 to the end of
      2004, were retrospectively analyzed. A mean nasal temperature of 30.8 degrees C
      +/- 2.1 degrees C was achieved. Three patients with sickle cell trait developed
      intraoperative hemoglobinuria, albeit with normal surrogate values for hemolysis.
      However, they had significantly lower mean hemoglobin levels during
      cardiopulmonary bypass compared to those sickle cell patients who did not exhibit
      hemoglobinuria (hemoglobin, 6.0 +/- 0.2 vs. 7.4 +/- 0.9 g x dL(-1), p < 0.01).
      Total drainage and blood transfusion requirements in patients with normal and
      sickle cell hemoglobin were similar. It was concluded that hypothermic
      cardiopulmonary bypass with cold cardioplegia is safe in sickle cell patients.
      Maintenance of adequate hemoglobin levels during cardiopulmonary bypass may be
      important to avoid triggering a sickling process.

PMID- 16432121
TI  - Above-knee vein harvest for coronary revascularization increases ASEPSIS score.
AB  - The long saphenous vein may be harvested from the thigh or the lower leg,
      depending on the operating surgeon's preference. This prospective study compared
      the incidence of altered wound healing between these two sites in 175 patients
      undergoing routine coronary artery bypass grafting over a 3-month period. The
      patients were divided into 3 groups. In group A, the vein harvest site was
      restricted to above the upper border of the patella. Group B included harvest
      sites that started at the ankle but extended above the level of the upper border
      of the patella. In group C, the vein harvest site was restricted to below the
      upper border of the patella. The wounds were assessed daily using the ASEPSIS
      scoring system. In group A, significantly more patients (24%) had an ASEPSIS
      score > 10, compared to group B (3%) and group C (2%). The mean ASEPSIS score was
      significantly lower in group C than groups A or B, 1.5 +/- 2.4 vs. 6.5 +/- 3.2 or
      3.7 +/- 1.7, respectively. The ASEPSIS score is reduced when vein harvest is
      restricted to below the level of the knee.

PMID- 16432122
TI  - A lethal complication of propofol.
AB  - High-dose propofol infusion for sedation of patients in the intensive care unit
      can result in rhabdomyolysis, acute renal failure, metabolic acidosis,
      hyperkalemia, ventricular arrhythmia, hyperthermia, and death. The death of a
      patient with such complications after lung biopsy is reported. Until a safer
      dosage range has been determined, propofol infusion at rates higher than 5 mg x
      kg(-1) x h(-1) should be discouraged for long-term sedation (> 48 h).

PMID- 16432123
TI  - Sewing needle in the heart.
AB  - An unusual case of a sewing needle in the heart is reported for its rarity. The
      relevant literature is briefly reviewed.

PMID- 16432124
TI  - Wide sleeve resection of lower trachea through anterior approach with omentopexy.
AB  - A 61-year-old man with tracheal adenoid cystic carcinoma (case 1) and a 28-year
      old woman with benign tracheal stenosis (case 2) were treated with sleeve
      resection of the lower trachea through a median sternotomy and prophylactic
      omental wrapping. The resected tracheas were 4.5 cm (case 1) and 4.0 cm (case 2)
      in length. Both patients had an uneventful course after surgery despite
      postoperative irradiation in case 1 and preoperative infection with methicillin
      resistant Staphylococcus aureus in case 2.

PMID- 16432125
TI  - Primary epithelioid angiosarcoma of the lung presenting as pulmonary hemorrhage.
AB  - Pulmonary angiosarcomas are usually secondary tumors, and only a few primary
      cases have been reported. We report a unique case of epithelioid angiosarcoma
      presenting as a solitary mass in the right upper lobe with pulmonary hemorrhage.
      Because of its epithelioid histology, this tumor may resemble a carcinoma or a
      variety of vascular lesions with epithelioid endothelial cells. Therefore, the
      diagnosis of epithelioid angiosarcoma should be based on immunohistochemical
      staining.

PMID- 16432126
TI  - New anastomosis assist devices for coronary artery bypass grafting.
AB  - Two new graft holders and an anastomosis assist mirror, designed for coronary
      artery bypass grafting, are described. The graft holders are pinching devices
      with sponges inside to prevent graft injury. The anastomosis assist mirror is a
      small circular mirror designed to show a reflective view of the lateral or
      posterior wall of the heart. Together they can provide secure stabilization of
      the graft and an excellent view of the anastomotic site.

PMID- 16432127
TI  - Update on drug-eluting stents for prevention of restenosis.
AB  - Despite the success of coronary stent implantations in the last decade, in-stent
      restenosis due to neointimal hyperplasia remains a problem to overcome.
      Neointimal hyperplasia is a vascular response to stent injury and mainly consists
      of proliferation of smooth muscle cells and deposition of extracellular matrix.
      Recently, local drug delivery has been advocated as a potential strategy to
      prevent in-stent restenosis. Unprecedented results have been obtained in early
      clinical studies on sirolimus-eluting and paclitaxel-eluting stents. Trials using
      various pharmaceutical coatings on different coronary stents are ongoing. More
      types of drug-eluting stents are expected on the market in the near future.
      Meanwhile, the evaluation of drug-eluting stents is entering the second phase in
      which the safety and efficacy in more complex lesion subsets and different
      clinical presentations are being investigated. Results including cost-benefit
      analyses are expected to have a tremendous impact on the practice of
      interventional cardiology in the next decade.

PMID- 16432128
TI  - Delayed pseudo-aneurysm of right coronary artery after indirect reimplantation.

PMID- 16432130
TI  - Pulmonary mucormycosis presenting as Horner's syndrome.

PMID- 16432129
TI  - Traumatic dislocated clavicle fracture with the oppression of superior vena cava.

PMID- 16432131
TI  - Double aortic arch causing tracheo-esophageal obstruction.

PMID- 16432132
TI  - Harmonic scalpel has acute beneficial effects during radial artery harvesting.

PMID- 16432133
TI  - Septal motion after PDA closure.

PMID- 16432134
TI  - Direct complications of sternal re-entry.

PMID- 16432135
TI  - A perspective on sporadic inclusion-body myositis: the role of aging and
      inflammatory processes.
AB  - Sporadic inclusion-body myositis (sIBM) is an age-related condition manifested
      after midlife. This review points out salient features of sIBM that are shared
      with normal aging in muscle and with inflammatory changes in vascular atheromas
      and senile plaques of Alzheimer disease (AD). The amyloid precursor protein (APP)
      and derived Abeta peptides are found in both AD and sIBM. Because transgenic
      expression of human APP induces sIBM like changes, it is of potential interest
      that an inducer of APP, IL-1, increases during aging in mouse muscle. Because
      various subsets of the usual aging changes in aging brain, muscle, and vessels
      can be attenuated in rodents by caloric intake and possibly in humans by drugs
      with anti-inflammatory and anticoagulant activities, this study suggests that
      diet and inflammation may be useful experimental variations in exploring the
      pathogenesis of sIBM.

PMID- 16432136
TI  - The unfolded protein response: a stress signaling pathway critical for health and
      disease.
AB  - The endoplasmic reticulum (ER) is an intracellular organelle consisting of a
      membranous labyrinth network that extends throughout the cytoplasm of the cell
      and is contiguous with the nuclear envelope. In all eukaryotic cells, the ER is
      the site where folding and assembly occurs for proteins destined to the
      extracellular space, plasma membrane, and the exo/endocytic compartments. The ER
      is exquisitely sensitive to alterations in homeostasis, and provides stringent
      quality control systems to ensure that only correctly folded proteins transit to
      the Golgi and unfolded or misfolded proteins are retained and ultimately
      degraded. A number of biochemical and physiologic stimuli, such as perturbation
      in calcium homeostasis or redox status, elevated secretory protein synthesis,
      expression of misfolded proteins, sugar/glucose deprivation, altered
      glycosylation, and overloading of cholesterol can disrupt ER homeostasis, impose
      stress to the ER, and subsequently lead to accumulation of unfolded or misfolded
      proteins in the ER lumen. The ER has evolved highly specific signaling pathways
      called the unfolded protein response (UPR) to cope with the accumulation of
      unfolded or misfolded proteins. Recent discoveries of the mechanisms of ER stress
      signaling have led to major new insights into the diverse cellular and
      physiologic processes that are regulated by the UPR. This review summarizes the
      complex regulation of UPR signaling and its relevance to human physiology and
      disease.

PMID- 16432137
TI  - Treatment and prevention of the amyloidoses: can the lessons learned be applied
      to sporadic inclusion-body myositis?
AB  - The amyloid fibril represents a final common pathologic pathway for a variety of
      human proteins, all of which have a propensity to misfold. Each seems to require
      a predisposing event to realize its fibrillogenic potential. It may be mutation,
      inappropriate or incomplete cleavage, overproduction, or the availability of a
      template for misfolding. Therapies have been based on decreasing the stimulus
      (inflammation in the case of AA) reducing the number of producing cells (AL) and
      a variety of approaches to removing the extracellular aggregates. Sporadic
      inclusion-body myositis (sIBM), while physically resembling the extracellular
      amyloidoses, is an intracellular disease, hence imposes the additional
      requirement of developing a therapy that can access and function inside the
      affected or potentially affected, cell. Current approaches to the treatment of
      other forms of amyloidosis are discussed in the context of their applicability,
      or lack thereof, to sIBM.

PMID- 16432139
TI  - Developing therapeutics for the diseases of protein misfolding.
AB  - Our current structural and biologic understanding of the misfolding diseases has
      restricted the development of therapies that target these diseases at a molecular
      level. The prion diseases are illustrative of this group of misfolding disorders
      and provide a model system for therapeutic intervention. Strategies to inhibit
      the replication and accumulation of the prion protein are being developed and
      have entered animal and clinical studies. Due to the underlying molecular basis
      of this disease class, many of the therapeutic approaches used to target prion
      misfolding have parallels in other misfolding diseases.

PMID- 16432138
TI  - RNA interference as potential therapy for neurodegenerative disease: applications
      to inclusion-body myositis?
AB  - The discovery of RNA interference (RNAi) has led to powerful new approaches to
      silence targeted genes in a sequence-specific manner. The potential therapeutic
      application of RNAi to neurologic disease is highlighted by the recent success of
      several laboratories in suppressing the expression of neurodegenerative disease
      genes in transgenic mouse models. Here I discuss potential applications of RNAi
      to inclusion-body myositis (IBM) after first reviewing its application more
      generally to neurologic disease. The clearest application of RNAi to IBM is as a
      research tool to identify critical target genes that contribute to pathogenesis.
      Provided that proximal pathogenic targets are identified, RNAi could surface as a
      potential therapeutic strategy to modulate their expression.

PMID- 16432140
TI  - Pilot trial of etanercept in the treatment of inclusion-body myositis.
AB  - Inclusion-body myositis (IBM) is an inflammatory muscle disease that has proven
      resistant to treatment. Tumor necrosis factor molecules have been detected in
      muscle biopsies from patients with IBM. Etanercept is a TNFalpha receptor fusion
      protein that binds and inactivates tumor necrosis factor. Nine patients were
      treated with etanercept at a dose of 25 mg, two times a week for an average of 17
      +/- 6.1 months. Each patient was evaluated using quantitative strength testing.
      Their data were compared to two different control groups. The first control group
      consisted of patients who participated in trials of beta-interferon-1A and had
      received placebo. There was no significant difference. The second control group
      was a natural history cohort of IBM patients. There was no statistically
      significant difference between the treated group and the natural history group at
      6 and 12 months when looking at elbow flexors, or 6 months when looking at hand
      grip. In the treated patients there was a small but significant improvement (p =
      0.002) in handgrip at 12 months.

PMID- 16432141
TI  - Inclusion-body myositis: clinical, diagnostic, and pathologic aspects.
AB  - The diagnostic aspects of sporadic inclusion-body myositis (s-IBM), and a few
      comments on our own approach to its treatment, are presented to foster the goals
      of this symposium, which was organized to provoke new ideas concerning the cause
      and treatment of this currently unsolvable disease. s-IBM is the most common,
      progressive, debilitating muscle disease beginning in persons over age 50 years,
      and it is more common in men. Diagnostic parameters reviewed are clinical, muscle
      biopsy histochemistry, electrophysiologic and CSF evaluations. Overall, the
      degenerative phenomena in s-IBM muscle fibers seem to be the major cause of the
      progressive, unstoppable weakness, rather than the lymphocytic inflammation.
      Available treatments are of only slight, temporary benefit for only some s-IBM
      patients, indicating a desperate need for definitive therapies.

PMID- 16432142
TI  - The current status of treatment for inclusion-body myositis.
AB  - There is no established treatment that improves, arrests, or slows the
      progression of inclusion-body myositis (IBM). Many anti-inflammatory,
      immunosuppressant, or immunomodulating agents have been administered to patients
      with IBM but the design of clinical trials was such that it can only be concluded
      that none produced rapid improvement. The natural history of the disease is for
      stabilization or improvement in a third of patients for 6 months or more. Thus
      some agents that did not produce dramatic benefit may have been prematurely
      abandoned. However, because high-dose prednisone worsens strength while
      decreasing inflammation but increases amyloid accumulation, alternative targets
      for intervention and novel treatment strategies are needed.

PMID- 16432143
TI  - Inflammatory, immune, and viral aspects of inclusion-body myositis.
AB  - Muscle biopsies from patients with sporadic inclusion-body myositis (sIBM)
      consistently demonstrate that the inflammatory T cells almost invariably invade
      intact (not vacuolated) fibers, whereas the vacuolated fibers are rarely invaded
      by T cells. This indicates two concurrently ongoing processes, an autoimmune
      mediated by cytotoxic T cells and a degenerative manifested by the vacuolated
      muscle fibers and deposits of amyloid-related proteins. The autoimmune features
      of IBM are highlighted by the strong association of the disease with: a) HLA I,
      II antigens, in frequency identical to classic autoimmune diseases; b) other
      autoimmune disorders in up to 32% of the patients, autoantibodies,
      paraproteinemias, or immunodeficiency; c) HIV and HTLV-I infection with
      increasingly recognized frequency (up to 13 known cases); and d) antigen
      specific, cytotoxic, and clonally expanded CD8+ autoinvasive T cells with
      rearranged T-cell receptor genes that persist over time, even in different
      muscles, and invade muscle fibers expressing MHC-I antigen and costimulatory
      molecules. In contrast to IBM, in various dystrophies the inflammatory cells are
      clonally diverse and the muscle fibers do not express MHC-I or costimulatory
      molecules in the pattern seen in IBM. Like other chronic autoimmune conditions
      with coexisting inflammatory and degenerative features (i.e., primary progressive
      MS), IBM is resistant to conventional immunotherapies. Recent data suggest that
      strong anti-T cell therapies can be promising and they are the focus of ongoing
      research.

PMID- 16432144
TI  - Inclusion-body myositis: a myodegenerative conformational disorder associated
      with Abeta, protein misfolding, and proteasome inhibition.
AB  - Sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older
      persons, is of unknown cause and there is no successful treatment. We summarize
      our most recent findings, which provide a better understanding of the steps in
      the pathogenetic cascade. We suggest that s-IBM is primarily a myodegenerative
      disease. Intriguing are the phenotypic similarities between s-IBM muscle fibers
      and the brains of Alzheimer disease, the most common neurodegenerative disease of
      older persons. In s-IBM, abnormal accumulation of the amyloid-beta (Abeta)
      precursor protein and its proteolytic fragment, Abeta, associated with the aging
      intracellular milieu of the muscle fiber, appear to be key upstream pathogenic
      events. We propose that the identified abnormal accumulation, misfolding, and
      aggregation of proteins, perhaps provoked by the aging milieu and aggravated by
      the oxidative stress, lead to the s-IBM-specific vacuolar degeneration and
      atrophy of muscle fibers.

PMID- 16432145
TI  - Mitochondrial abnormalities in inclusion-body myositis.
AB  - Mitochondrial changes are frequently encountered in sporadic inclusion-body
      myositis (s-IBM). Cytochrome c oxidase (COX)-deficient muscle fibers and large
      scale mitochondrial DNA (mtDNA) deletions are more frequent in s-IBM than in age
      matched controls. COX deficient muscle fibers are due to clonal expansion of
      mtDNA deletions and point mutations in segments of muscle fibers. Such segments
      range from 75 microm to more than 1,000 microm in length. Clonal expansion of the
      4977 bp "common deletion" is a frequent cause of COX deficient muscle fiber
      segments, but many other deletions also occur. The deletion breakpoints cluster
      in a few regions that are similar to what is found in human mtDNA deletions in
      general. Analysis in s-IBM patients of three nuclear genes associated with
      multiple mtDNA deletions, POLG1, ANT1 and C10orf2, failed to demonstrate any
      mutations. In s-IBM patients with high number of COX-deficient fibers, the
      impaired mitochondrial function probably contribute to muscle weakness and
      wasting. Treatment that has positive effects in mitochondrial myopathies may be
      tried also in s-IBM.

PMID- 16432146
TI  - Controlling autoimmunity in sporadic inclusion-body myositis.

PMID- 16432148
TI  - Inclusion-body myositis and Alzheimer disease: two sides of the same coin, or
      different currencies altogether?

PMID- 16432147
TI  - Immunotherapeutic relief from persistent infections and amyloid disorders.
AB  - Persistent infections and amyloid disorders afflict a significant number of
      people worldwide. It would appear at first glance that the treatment of these
      afflictions should be entirely unrelated; however, in both cases components of
      the adaptive immune system have been harnessed in an attempt to provide some
      therapeutic relief. Given that the ability of a pathogen to establish persistence
      often depends in part on a shortcoming of the adaptive immune response, it seems
      logical to devise immunotherapies with the intention of supplementing (or
      replacing) the insufficient immunologic element. A case in point is an
      intervention referred as immunocytotherapy, which relies upon the adoptive
      transfer of pathogen-specific T lymphocytes into a persistently infected host.
      Remarkably, the adoptively transferred T lymphocytes not only have the capacity
      to clear the persistent infection, but can also provide the recipient with
      protection against subsequent rechallenge (i.e., immunologic memory). Treatment
      of amyloid disorders (e.g., Alzheimer disease, sporadic inclusion-body myositis)
      with a similar therapeutic approach is complicated by the fact that the aberrant
      protein accumulations are self-derived. Focusing the adaptive response on these
      aberrant self-proteins has the potential to result in autoimmune pathology. This
      review critically evaluates the importance of immunotherapeutic approaches for
      the treatment of persistent infections and amyloid disorders, and attempts to
      delineate the interventions that are most likely to succeed in an exceedingly
      complex disorder such as sporadic inclusion-body myositis.

PMID- 16432150
TI  - The ubiquitin proteolytic system: from a vague idea, through basic mechanisms,
      and onto human diseases and drug targeting.

PMID- 16432149
TI  - Amyloidogenic processing of beta-amyloid precursor protein in intracellular
      compartments.
AB  - Trafficking and proteolytic processing of amyloid precursor protein (APP) have
      been the focus of numerous investigations in the past two decades, since the
      identification of Abeta as the principal component of brain senile plaques and
      the cloning of APP cDNA. Tremendous progress has been made in the recent past
      toward the characterization of beta- and gamma-secretases. Here, we review the
      salient features of Alzheimer disease amyloidogenesis, and discuss the current
      knowledge on APP trafficking and amyloidogenic processing of APP in intracellular
      membrane compartments and microdomains.

PMID- 16432151
TI  - Common structure and toxic function of amyloid oligomers implies a common
      mechanism of pathogenesis.
AB  - Recent findings indicate that soluble amyloid oligomers may represent the primary
      pathologic species in degenerative diseases. These amyloid oligomers share common
      structural features and the ability to permeabilize membranes, suggesting that
      they also share a common primary mechanism of pathogenesis. Membrane
      permeabilization by amyloid oligomers may initiate a common group of downstream
      pathologic processes, including intracellular calcium dyshomeostasis, production
      of reactive oxygen species, altered signaling pathways, and mitochondrial
      dysfunction that represent key effectors of cellular dysfunction and cell death
      in amyloid-associated degenerative disease, such as sporadic inclusion-body
      myositis.

PMID- 16432152
TI  - Apolipoprotein E and Alzheimer disease.
AB  - Apolipoprotein (apo) E, a multifunctional protein with central roles in lipid
      metabolism and neurobiology, has three common isoforms (apoE2, apoE3, and apoE4)
      with different effects on lipid homeostasis and neurobiology. Unlike apoE3, the
      most common isoform, apoE4, is associated with increased risk of developing
      Alzheimer disease (AD) and other neurodegenerative disorders. Although the
      mechanisms underlying apoE4's action in AD pathogenesis are still poorly
      understood, emerging data strongly suggest that apoE4 contributes to this disease
      by interacting with different factors through various pathways. Thus, multiple
      molecular and cellular mechanisms should be considered when anti-AD drugs are
      developed based on apoE studies.

PMID- 16432153
TI  - Frameshift proteins in autosomal dominant forms of Alzheimer disease and other
      tauopathies.
AB  - Frameshift (+1) proteins such as APP(+1) and UBB(+1) accumulate in sporadic cases
      of Alzheimer disease (AD) and in older subjects with Down syndrome (DS). We
      investigated whether these proteins also accumulate at an early stage of
      neuropathogenesis in young DS individuals without neuropathology and in early
      onset familial forms of AD (FAD), as well as in other tauopathies, such as Pick
      disease (PiD) or progressive supranuclear palsy (PSP). APP(+1) is present in many
      neurons and beaded neurites in very young cases of DS, which suggests that it is
      axonally transported. In older DS patients (>37 years), a mixed pattern of
      APP(+1) immunoreactivity was observed in healthy looking neurons and neurites,
      dystrophic neurites, in association with neuritic plaques, as well as
      neurofibrillary tangles. UBB(+1) immunoreactivity was exclusively present in AD
      type of neuropathology. A similar pattern of APP(+1) and UBB(+1) immunoreactivity
      was also observed for FAD and much less explicit in nondemented controls after
      the age of 51 years. Furthermore, we observed accumulation of +1 proteins in
      other types of tauopathies, such as PiD, frontotemporal dementia, PSP and
      argyrophylic grain disease. These data suggest that accumulation of +1 proteins
      contributes to the early stages of dementia and plays a pathogenic role in a
      number of diseases that involve the accumulation of tau.

PMID- 16432154
TI  - Preferential degradation of oxidized proteins by the 20S proteasome may be
      inhibited in aging and in inflammatory neuromuscular diseases.
AB  - Free radicals produced by chronic inflammation cause cumulative damage to
      cellular macromolecules and appear to contribute to senescence/aging, age-related
      disorders, and neuromuscular degenerative diseases such as inclusion-body
      myositis. Proteins are major targets for oxidative damage (in addition to DNA and
      lipids) and the accumulation of oxidized proteins has been reported in many aging
      and disease models. In young and healthy individuals, moderately oxidized soluble
      cell proteins are selectively and rapidly degraded by the 20S proteasome. The
      mechanism of selective proteolysis appears to depend upon oxidation-induced
      protein unfolding, with increasing surface hydrophobicity as (previously
      shielded) hydrophobic residues are exposed from the interior. The 20S proteasome
      can preferentially bind to and degrade such mildly oxidized, hydrophobic proteins
      without a need for ubiquitin targeting or ATP activation. Severely oxidized,
      aggregated, and crosslinked proteins, however, are poor substrates for
      degradation and actually inhibit the proteasome. During aging, and in many age
      related diseases/disorders, the proteasome is progressively inhibited by binding
      to increasing levels of oxidized and cross-linked protein aggregates. Cellular
      aging and inflammatory neuromuscular degenerative diseases probably include both
      an increase in the generation of reactive oxygen species as well as a decline in
      proteasome activity, resulting in the progressive accumulation of oxidatively
      damaged protein aggregates that eventually contribute to cellular dysfunction and
      senescence.

PMID- 16432157
TI  - AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor
      growth in a mouse model.
AB  - IFN-inducible proteins are known to mediate IFN-directed antitumor effects. The
      human IFN-inducible protein absent in melanoma 2 (AIM2) gene encodes a 39-kDa
      protein, which contains a 200-amino-acid repeat as a signature of HIN-200 family
      (hematopoietic IFN-inducible nuclear proteins). Although AIM2 is known to inhibit
      fibroblast cell growth in vitro, its antitumor activity has not been shown. Here,
      we showed that AIM2 expression suppressed the proliferation and tumorigenicity of
      human breast cancer cells, and that AIM2 gene therapy inhibited mammary tumor
      growth in an orthotopic tumor model. We further showed that AIM2 significantly
      increased sub-G(1) phase cell population, indicating that AIM2 could induce tumor
      cell apoptosis. Moreover, AIM2 expression greatly suppressed nuclear factor
      kappaB transcriptional activity and desensitized tumor necrosis factor-alpha
      mediated nuclear factor-kappaB activation. Together, these results suggest that
      AIM2 associates with tumor suppression activity and may serve as a potential
      therapeutic gene for future development of AIM2-based gene therapy for human
      breast cancer.

PMID- 16432155
TI  - Brain and brawn: parallels in oxidative strength.
AB  - Neuronal oxidative stress occurs early in the progression of Alzheimer disease
      (AD), significantly before the development of the pathologic hallmarks,
      neurofibrillary tangles, and senile plaques. Study of Down syndrome, cases with
      autosomal dominant mutation, and sporadic AD all suggest amyloid-beta deposition
      and hyperphosphorylated tau function as compensatory responses and downstream
      adaptations to ensure that neuronal cells do not succumb to oxidative damage.
      Amyloid-beta and tau hyperphosphorylation also define vulnerable muscle cells in
      sporadic inclusion-body myositis (s-IBM). The role of the structural changes of s
      IBM, as in AD, remains to be determined but may mark a critical response yielding
      a novel balance in oxidant homeostasis.

PMID- 16432159
TI  - Restoration of p53 function for selective Fas-mediated apoptosis in human and rat
      glioma cells in vitro and in vivo by a p53 COOH-terminal peptide.
AB  - We have shown that a COOH-terminal peptide of p53 (amino acids 361-382, p53p),
      linked to the truncated homeobox domain of Antennapedia (Ant) as a carrier for
      transduction, induced rapid apoptosis in human premalignant and malignant cell
      lines. Here, we report that human and rat glioma lines containing endogenous
      mutant p53 or wild-type (WT) p53 were induced into apoptosis by exposure to this
      peptide called p53p-Ant. The peptide was comparatively nontoxic to proliferating
      nonmalignant human and rat glial cell lines containing WT p53 and proliferating
      normal human peripheral marrow blood stem cells. Degree of sensitivity to the
      peptide correlated directly with the level of endogenous p53 expression and
      mutant p53 conformation. Apoptosis induction by p53p-Ant was quantitated by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and
      Annexin V staining in human glioma cells in vitro and in a syngeneic orthotopic
      9L glioma rat model using convection-enhanced delivery in vivo. The mechanism of
      cell death by this peptide was solely through the Fas extrinsic apoptotic
      pathway. p53p-Ant induced a 3-fold increase in extracellular membrane Fas
      expression in glioma cells but no significant increase in nonmalignant glial
      cells. These data suggest that p53 function for inducing Fas-mediated apoptosis
      in gliomas, which express sufficient quantities of endogenous mutant or WT p53,
      may be restored or activated, respectively, by a cell-permeable peptide derived
      from the p53 COOH-terminal regulatory domain (p53p-Ant). p53p-Ant may serve as a
      prototypic model for the development of new anticancer agents with unique
      selectivity for glioma cancer cells and it can be successfully delivered in vivo
      into a brain tumor by a convection-enhanced delivery system, which circumvents
      the blood-brain barrier.

PMID- 16432158
TI  - Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in
      response to interleukin-6 receptor and epidermal growth factor receptor signaling
      through JAK and/or MEK in head and neck squamous cell carcinomas.
AB  - Signal transducer and activator of transcription 3 (STAT3) has been reported to
      be activated by interleukin-6 receptor (IL-6R) or epidermal growth factor
      receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), which may have
      important implications for responsiveness to therapeutics targeted at EGFR, IL
      6R, or intermediary kinases. Suppressor of cytokine signaling-1 (SOCS-1) has been
      implicated recently in the negative regulation of IL-6R/Janus-activated kinase
      (JAK)-mediated activation of STAT3, suggesting that SOCS-1 could affect
      alternative activation of STAT3 by EGFR, IL-6R, and associated kinases. We
      investigated whether epigenetic modification of SOCS-1 affects STAT3 activation
      in response to IL-6R-, EGFR-, JAK-, or mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase (MEK)-mediated signal
      activation. STAT3 was predominantly activated by IL-6R via Jak1/Jak2 in HNSCC
      lines UMSCC-9 and UMSCC-38 in association with transcriptional silencing of SOCS
      1 by hypermethylation. In UMSCC-11A cells with unmethylated SOCS-1, STAT3
      activation was regulated by both EGFR and IL-6R via a JAK-independent pathway
      involving MEK. Pharmacologic inhibitors of JAK and MEK and expression of SOCS-1
      following demethylation or transient transfection inhibited STAT3 activation and
      cell proliferation and induced cell apoptosis in corresponding cell lines.
      Hypermethylation of SOCS-1 was found in about one-third of human HNSCC tissues,
      making it a potentially relevant marker for STAT-targeted therapy in HNSCC
      patients. We conclude that SOCS-1 methylation status can differentially affect
      STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and
      response to pharmacologic antagonists. Identifying the potential factors and the
      regulatory pathways in STAT3 activation has important implications for the
      development and selection of molecularly targeted therapy in HNSCC.

PMID- 16432161
TI  - Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice
      liver and small intestine by cancer chemopreventive agent curcumin.
AB  - Curcumin has been shown to prevent and inhibit carcinogen-induced tumorigenesis
      in different organs of rodent carcinogenesis models. Our objective is to study
      global gene expression profiles elicited by curcumin in mouse liver and small
      intestine as well as to identify curcumin-regulated nuclear factor E2-related
      factor 2 (Nrf2)-dependent genes. Wild-type C57BL/6J and Nrf2 knockout
      C57BL/6J/Nrf2(-/-) mice were given a single oral dose of curcumin at 1,000 mg/kg.
      Liver and small intestine were collected at 3 and 12 hours after treatments.
      Total RNA was extracted and analyzed using Affymetrix (Santa Clara, CA) mouse
      genome 430 array (45K) and GeneSpring 6.1 software (Silicon Genetics, Redwood
      City, CA). Genes that were induced or suppressed >2-fold by curcumin treatments
      compared with vehicle in wild-type mice but not in knockout mice were filtered
      using GeneSpring software and regarded as Nrf2-dependent genes. Among those well
      defined genes, 822 (664 induced and 158 suppressed) and 222 (154 induced and 68
      suppressed) were curcumin-regulated Nrf2-dependent genes identified in the liver
      and small intestine, respectively. Based on their biological functions, these
      genes can be classified into the category of ubiquitination and proteolysis,
      electron transport, detoxification, transport, apoptosis and cell cycle control,
      cell adhesion, kinase and phosphatase, and transcription factor. Many phase II
      detoxification/antioxidant enzyme genes, which are regulated by Nrf2, are among
      the identified genes. The identification of curcumin-regulated Nrf2-dependent
      genes not only provides potential novel insights into the biological effects of
      curcumin on global gene expression and chemoprevention but also points to the
      potential role of Nrf2 in these processes.

PMID- 16432162
TI  - Targeted delivery of methotrexate to epidermal growth factor receptor-positive
      brain tumors by means of cetuximab (IMC-C225) dendrimer bioconjugates.
AB  - We have constructed a drug delivery vehicle that targets the epidermal growth
      factor receptor (EGFR) and its mutant isoform EGFRvIII. The monoclonal antibody,
      cetuximab, previously known as C225, which binds to both EGFR and EGFRvIII, was
      covalently linked via its Fc region to a fifth-generation (G5) polyamidoamine
      dendrimer containing the cytotoxic drug methotrexate. As measured by mass
      spectrometry and UV/vis spectroscopy, the resulting bioconjugate, designated C225
      G5-MTX, contained 12.6 molecules of methotrexate per unit of dendrimer. Specific
      binding and cytotoxicity of the bioconjugate was evaluated against the EGFR
      expressing rat glioma cell line F98(EGFR). Using a competitive binding assay, it
      was shown that the bioconjugate retained its affinity for F98(EGFR) cells, with a
      0.8 log unit reduction in its EC(50). Only cetuximab completely inhibited binding
      of the bioconjugate, which was unaffected by methotrexate or dendrimer. Cetuximab
      alone was not cytotoxic to F98(EGFR) cells at the concentration tested, whereas
      the IC(50) of the bioconjugate was 220 nmol/L, which was a 2.7 log unit decrease
      in toxicity over that of free methotrexate. The biodistribution of C225-G5-MTX in
      rats bearing i.c. implants of either F98(EGFR) or F98(WT) gliomas was determined
      24 hours following convection enhanced delivery of (125)I-labeled bioconjugate.
      At this time, 62.9 +/- 14.7% ID/g tumor was localized in rats bearing F98(EGFR)
      gliomas versus 11.3 +/- 3.6% ID/g tumor in animals bearing F98(WT) gliomas,
      thereby showing specific molecular targeting of the tumor. The corresponding
      radioactivity of normal brain from the F98(EGFR) tumor-bearing right and non
      tumor-bearing left cerebral hemisphere were 5.8 +/- 3.4% and 0.8 +/- 0.6% ID/g,
      respectively. Based on these results, therapy studies were initiated in F98(EGFR)
      glioma-bearing rats. Animals that received C225-G5-MTX, cetuximab, or free
      methotrexate had median survival times of 15, 17, and 19.5 days, respectively,
      which were not statistically different from each other or untreated control
      animals. Our results, which are both positive and negative, show that specific
      molecular targeting is but one of several requirements that must be fulfilled if
      an antibody-drug bioconjugate will be therapeutically useful.

PMID- 16432160
TI  - Inhibition of TRIP1/S8/hSug1, a component of the human 19S proteasome, enhances
      mitotic apoptosis induced by spindle poisons.
AB  - Mitotic spindle poisons (e.g., Taxol and vinblastine), used as chemotherapy
      drugs, inhibit mitotic spindle function, activate the mitotic spindle checkpoint,
      arrest cells in mitosis, and then cause cell death by mechanisms that are poorly
      understood. By expression cloning, we identified a truncated version of human
      TRIP1 (also known as S8, hSug1), an AAA (ATPases associated with diverse cellular
      activities) family ATPase subunit of the 19S proteasome regulatory complex, as an
      enhancer of spindle poison-mediated apoptosis. Stable expression of the truncated
      TRIP1/S8/hSug1 in HeLa cells [OP-TRIP1(88-406)] resulted in a decrease of
      measurable cellular proteasome activity, indicating that OP-TRIP1(88-406) had a
      dominant-negative effect on proteasome function. OP-TRIP1(88-406) revealed an
      increased apoptotic response after treatment with spindle poisons or with
      proteasome inhibitors. The increased apoptosis coincided with a significant
      decrease in expression of BubR1, a kinase required for activation and maintenance
      of the mitotic spindle checkpoint in response to treatment with spindle poisons.
      Small interfering RNA (siRNA)-mediated knockdown of TRIP1/S8/hSug1 resulted in a
      reduction of general proteasome activity and an increase in mitotic index. The
      siRNA treatment also caused increased cell death after spindle poison treatment.
      These results indicate that inhibition of TRIP1/S8/hSug1 function by expression
      of a truncated version of the protein or by siRNA-mediated suppression enhances
      cell death in response to spindle poison treatment. Current proteasome inhibitor
      drugs in trial as anticancer agents target elements of the 20S catalytic
      subcomplex. Our results suggest that targeting the ATPase subunits in 19S
      regulatory complex in the proteasome may enhance the antitumor effects of spindle
      poisons.

PMID- 16432163
TI  - The sulindac derivatives OSI-461, OSIP486823, and OSIP487703 arrest colon cancer
      cells in mitosis by causing microtubule depolymerization.
AB  - Exisulind (sulindac sulfone) and three highly potent derivatives, OSI-461
      (CP461), OSIP486823 (CP248), and OSIP487703, inhibit growth and induce apoptosis
      in SW480 human colon cancer cells, with IC(50)s of 200, 2, 0.1, and 0.003
      micromol/L, respectively. The latter three compounds, but not exisulind, induce
      marked M-phase cell cycle arrest in these cells. This effect seems to be
      independent of the known ability of these compounds to cause activation of
      protein kinase G. When tested at twice their IC(50) concentration for growth
      inhibition, OSI-461, OSIP486823, and OSIP487703 cause depolymerization of
      microtubules in interphase cells, inhibit spindle formation in mitotic cells, and
      induce multinucleated cells. In vitro tubulin polymerization assays indicate that
      all three compounds interact with tubulin directly to cause microtubule
      depolymerization and/or inhibit de novo tubulin polymerization. These results
      suggest that the dual effects of OSI-461, OSIP486823, and OSIP487703 on
      impairment of microtubule functions and protein kinase G activation may explain
      the potent antiproliferative and apoptotic effects of these compounds in cancer
      cells.

PMID- 16432164
TI  - Enhancement of DNA topoisomerase I inhibitor-induced apoptosis by ursodeoxycholic
      acid.
AB  - Certain hydrophobic bile acids, including deoxycholic acid and chenodeoxycholic
      acid, exert toxic effects not only in the liver but also in the intestine.
      Moreover, ursodeoxycholic acid (UDCA), which has protective actions against
      apoptosis in the liver, may have both protective and toxic effects in the
      intestine. The goal of the present study was to clarify the mechanisms
      responsible for the toxic effect of UDCA in intestinal HT-29 cells. Here, we show
      that UDCA potentiated both phosphatidylserine externalization and
      internucleosomal DNA fragmentation induced by SN-38, the most potent metabolite
      of the DNA topoisomerase I inhibitor, CPT-11. Furthermore, the loss of
      mitochondrial membrane potential as well as mitochondrial membrane permeability
      transition induced by SN-38 was enhanced in the presence of UDCA, resulting in an
      increased lethality determined by colony-forming assay. This UDCA-induced
      increased apoptosis was not due to alteration of either intracellular
      accumulation of SN-38 or cell cycle arrest by SN-38. The increased apoptosis was
      best observed when UDCA was present after SN-38 stimulation and was independent
      of caspase-8 but dependent on caspase-9 and caspase-3 activation. Furthermore,
      UDCA enhanced SN-38-induced c-Jun NH(2)-terminal kinase activation. In
      conclusion, UDCA increases the apoptotic effects while decreasing the necrotic
      effects of SN-38 when added after the topoisomerase I inhibitor, showing
      potential clinical relevance as far as targeted cell death and improved wound
      healing are concerned. However, the use of this bile acid as an enhancer in
      antitumor chemotherapy should be further evaluated clinically.

PMID- 16432165
TI  - Improvement by solid dispersion of the bioavailability of KRN633, a selective
      inhibitor of VEGF receptor-2 tyrosine kinase, and identification of its potential
      therapeutic window.
AB  - KRN633 is a potent inhibitor of vascular endothelial growth factor (VEGF)
      receptor tyrosine kinases. However, it is poorly water-soluble; consequently,
      relatively high doses are required to achieve substantial in vivo tumor growth
      suppression after oral administration. We subjected KRN633 to the solid
      dispersion technique to improve its solubility, absorption, and antitumor
      efficacy after oral administration. This technique transformed the drug into an
      amorphous state and dramatically improved its dissolution rate. It also enhanced
      the bioavailability of the drug in rats by approximately 7.5-fold. The solid
      dispersion form of KRN633 also dramatically inhibited human tumor growth in
      murine and rat xenograft models: similar rates of tumor growth inhibition were
      obtained with 10- to 25-fold lower doses of the solid dispersion preparation
      relative to the pure drug in its crystalline state. Histologic analysis of tumors
      treated with the solid dispersion preparation revealed a significant reduction in
      microvessel density at much lower doses when compared with the crystalline form
      preparation. In addition, a dose-finding study using the solid dispersion form in
      a rat xenograft model revealed that there was a substantial range of doses at
      which KRN633 in the solid dispersion form showed significant antitumor activity
      but did not induce weight loss or elevate total urinary protein levels. These
      data suggest that the solid dispersion technique is an effective approach for
      developing KRN633 drug products and that KRN633 in the solid dispersion form may
      be a highly potent, orally available drug with a wide therapeutic window for
      diseases associated with abnormal angiogenesis.

PMID- 16432166
TI  - Antitumor efficacy of a urokinase activation-dependent anthrax toxin.
AB  - Previously, we have generated a potent prodrug consisting of modified anthrax
      toxins that is activated by urokinase plasminogen activator (uPA). The
      cytotoxicity of the drug, PrAg-U2 + FP59, is dependent on the presence of
      receptor-associated uPA activity. Local intradermal administration of PrAg-U2 +
      FP59 adjacent to the tumor nodules in mice with transplanted solid tumors had a
      potent antitumor effect. In succession of these experiments, we have now
      investigated the systemic antitumor efficacy of PrAg-U2 + FP59. C57Bl/6J mice
      bearing syngenic tumors derived from B16 melanoma, T241 fibrosarcoma, or Lewis
      lung carcinoma cells were treated with different mass ratios and doses of PrAg-U2
      + FP59. Tumor volumes were recorded daily by caliper measurements. In some
      experiments, dexamethasone was coadministered. Our data show a significant
      antitumor effect of systemic administration of PrAg-U2 + FP59 in three syngenic
      tumor models. Optimal antitumor effect and low toxicity was obtained with a 25:1
      mass ratio between the two components (PrAg-U2 and FP59). The experiments show
      that PrAg-U2 + FP59 displays a clear dose-response relationship with regard to
      both antitumor efficacy and systemic toxicity. Dose-limiting toxicity seemed to
      be due to activation of the prodrug by uPA and its receptor in the intestinal
      mucosa. Concurrent treatment with dexamethasone was found to prevent dose
      limiting toxicity. Taken together, these data indicate that uPA-activated toxins
      may be promising candidates for targeted therapy of human cancers that
      overexpress uPA and its receptor.

PMID- 16432167
TI  - New enzyme for reductive cancer chemotherapy, YieF, and its improvement by
      directed evolution.
AB  - Reductive prodrugs, mitomycin C and 5-aziridinyl-2,4-dinitrobenzamide (CB 1954),
      are nontoxic in their native form but become highly toxic upon reduction. Their
      effectiveness in cancer chemotherapy can be enhanced by delivering to tumors
      enzymes with improved prodrug reduction kinetics. We report the discovery of a
      new prodrug-reducing enzyme, YieF, from Escherichia coli, and the improvement of
      its kinetics for reducing mitomycin C and CB 1954. A YieF-derived enzyme, Y6,
      killed HeLa spinner cells with >or=5-fold efficiency than the wild-type enzymes,
      YieF and NfsA, at a variety of drug and enzyme concentrations and incubation
      times. With adhered HeLa cells and Salmonella typhimurium SL 7838 bacteria as
      enzyme delivery vehicle, at least an order of magnitude less of Y6-producing
      bacteria were required to kill >90% of tumor cells compared with bacteria
      expressing the wild-type enzymes, which at a comparable level killed < 5% of the
      cells. Thus, Y6 is a promising enzyme for use in cancer chemotherapy, and
      Salmonella strain SL 7838, which specifically targets tumors, may be used to
      deliver the prodrug-activating enzymes to tumors.

PMID- 16432168
TI  - Cetuximab preclinical antitumor activity (monotherapy and combination based) is
      not predicted by relative total or activated epidermal growth factor receptor
      tumor expression levels.
AB  - Although Erbitux (cetuximab) has proven therapeutic benefit in the clinical
      setting, the molecular determinants predicting responsiveness to this agent are
      still not very well understood. Here, we assessed the relationship between basal
      total and activated (pY1068) epidermal growth factor receptor (EGFR) levels in a
      tumor and the responsiveness to cetuximab monotherapy or combination-based
      treatment using human xenograft models. Cetuximab treatment alone (0.25-1
      mg/mouse/injection, q3d, i.p.) effectively delayed the growth of GEO and L2987
      tumors by a minimum of 10 days corresponding to log cell kill values of >or=1.0.
      Borderline activity was seen in the A549 and WiDr xenografts. However, cetuximab
      failed to show any significant antitumor activity in the HT29, HCT116, LOVO,
      Colo205, LX-1, HCC70, and N87 models. All of the studied tumors had detectable
      yet variable levels of EGFR. For combination regimens, cetuximab (1
      mg/mouse/injection, q3dx5, i.p.) and cisplatin (4.5 mg/kg/injection, q3dx5, i.v.)
      proved to be significantly more efficacious than individual monotherapies in the
      cisplatin-refractory yet cetuximab-responsive GEO tumor model (P < 0.001).
      However, no therapeutic enhancement was observed in the cisplatin and cetuximab
      weakly responsive A549 xenograft. Similarly, combinations of CPT-11 (48
      mg/kg/injection, q3dx5, i.v.) with cetuximab (1 mg/mouse/injection, q3dx5, i.p.)
      failed to show any improvements over individual monotherapies in the cetuximab
      resistant/weakly responsive HT29, A549, and WiDr models. We conclude that
      preclinical activity associated with cetuximab monotherapy does not correlate
      directly with relative basal levels of total or activated (pY1068) EGFR in a
      tumor. Moreover, robust single-agent activity by cetuximab may be the best
      predictor for this agent to potentiate chemotherapy-mediated antitumor
      activities.

PMID- 16432169
TI  - Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that
      potently inhibit the IGF receptor type I signal transduction function.
AB  - The insulin-like growth factor (IGF) system plays an important role in a variety
      of physiologic processes and in diseases such as cancer. Although the role of the
      IGF system in cancer has been recognized many years ago, components of the system
      have only recently been targeted and shown to affect cell transformation,
      proliferation, survival, motility, and migration in tissue cultures and in mouse
      models of cancer. We have been hypothesizing that targeting IGF-II in addition to
      blocking its interaction with the IGF receptor type I (IGF-IR) would also allow
      to block that portion of the signal transduction through the insulin receptor
      that is due to its interaction with IGF-II. Lowering its level may also not
      induce up-regulation of its production as for IGF-I. Finally, targeting a
      diffusable ligand as IGF-II may not require penetration of the antibody inside
      tumors but could shift the equilibrium to IGF-II complexed with antibody so the
      ligand concentration would decrease in the tumor environment without the need for
      the antibody to penetrate the tumor. Here, we describe the identification and
      characterization of three novel anti-IGF-II fully human monoclonal antibodies.
      They bound with high (subnanomolar) affinity to IGF-II, did not cross-react with
      IGF-I and insulin, and potently inhibited signal transduction mediated by the IGF
      IR interaction with IGF-II. The most potent neutralizer, IgG1 m610, inhibited
      phosphorylation of the IGF-IR and the insulin receptor, as well as
      phosphorylation of the downstream kinases Akt and mitogen-activated protein
      kinase with an IC(50) of the order of 1 nmol/L at IGF-II concentration of 10
      nmol/L. It also inhibited growth of the prostate cancer cell line DU145 and
      migration of the breast cancer line cells MCF-7. These results indicate an
      immunotherapeutic potential of IgG1 m610 likely in combination with other
      antibodies and anticancer drugs but only further experiments in mouse models of
      cancer and human clinical trials could evaluate this possibility.

PMID- 16432170
TI  - Differential competitive resistance to methylating versus chloroethylating agents
      among five O6-alkylguanine DNA alkyltransferases in human hematopoietic cells.
AB  - P140K-MGMT and G156A-MGMT genes encode two O(6)-benzylguanine-resistant O(6)
      alkylguanine DNA alkyltransferase proteins that confer a high degree of O(6)
      benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or O(6)
      benzylguanine and temozolomide resistance to primary hematopoietic cells. In this
      study, we directly compared these and three other O(6)-benzylguanine-resistant
      MGMT genes for their ability to protect the human erythroleukemia cell line,
      K562, using a direct competitive selection strategy to identify the mutation that
      conferred the greatest degree of protection from O(6)-benzylguanine and either
      BCNU or temozolomide. MFG retroviral vector plasmids for each of these mutants
      [G156A-MGMT (ED(50) for O(6)-benzylguanine, 60 micromol/L); and P140K-MGMT, MGMT
      2 (S152H, A154G, Y158H, G160S, L162V), MGMT-3 (C150Y, A154G, Y158F, L162P,
      K165R), and MGMT-5 (N157T, Y158H, A170S; ED(50) for benzylguanine, >1,000
      micromol/L)] were mixed, and the virus produced from Phoenix cells was transduced
      into K562 cells. Stringent selection used high doses of O(6)-benzylguanine (800
      micromol/L) and temozolomide (1,000 micromol/L) or BCNU (20 micromol/L)
      administered twice, and following regrowth, surviving clones were isolated, and
      the MGMT transgene was sequenced. None of the mutants was lost during selection.
      Using temozolomide, the enrichment factor was greatest for P140K-MGMT (1.7-fold).
      Using BCNU selection, the greatest enrichment was observed with MGMT-2 (1.5
      fold). G156A-MGMT, which is the least O(6)-benzylguanine-resistant MGMT gene of
      the mutants tested, was not lost during selection but was selected against. The
      optimal mutant MGMT useful as a drug resistance gene may depend on whether a
      methylating or chloroethylating agent is used for drug selection.

PMID- 16432171
TI  - Novel angiogenic inhibitor DN-9693 that inhibits post-transcriptional induction
      of connective tissue growth factor (CTGF/CCN2) by vascular endothelial growth
      factor in human endothelial cells.
AB  - Connective tissue growth factor (CTGF/CCN2) is a potent angiogenic factor. In
      this report, we describe for the first time that vascular endothelial growth
      factor (VEGF)-mediated induction of the ctgf/ccn2 gene was a post-transcriptional
      event that was inhibited by a novel angiogenic inhibitor, DN-9693, in human
      umbilical vein endothelial cells. Steady-state mRNA levels of ctgf/ccn2 were
      remarkably increased by VEGF in a concentration-dependent manner, whereas the
      activity of the ctgf/ccn2 promoter was not responsive to VEGF as confirmed by a
      reporter gene assay and quantitative real-time PCR analysis. By employing a RNA
      degradation assay, we eventually found that the observed increase in the
      ctgf/ccn2 mRNA level was due to an increased stability of the mRNA induced by
      VEGF. DN-9693 at a dose of 0.1 to 2 ng/mL did not affect basal levels of
      ctgf/ccn2 mRNA; however, enhancement of ctgf/ccn2 mRNA expression by VEGF was
      specifically inhibited by DN-9693. Of importance, the inhibitory effects could be
      also ascribed to post-transcriptional regulation, because the VEGF-mediated
      increase in stability of ctgf/ccn2 mRNA was suppressed by DN-9693. Furthermore,
      we investigated the effects of DN-9693 on VEGF-induced activation of three
      subgroups of mitogen-activated protein kinase pathways and found that DN-9693
      blocked the activation of these pathways by VEGF. These results suggest that VEGF
      increases ctgf/ccn2 mRNA stability through mitogen-activated protein kinase
      mediated intracellular signaling cascade(s), which can be inhibited
      posttranscriptionally by a novel angiogenic inhibitor, DN-9693, in human
      umbilical vein endothelial cells.

PMID- 16432172
TI  - Flavopiridol disrupts STAT3/DNA interactions, attenuates STAT3-directed
      transcription, and combines with the Jak kinase inhibitor AG490 to achieve
      cytotoxic synergy.
AB  - Up-regulated signal transducers and activators of transcription (STAT)-mediated
      signaling is believed to contribute to the pathogenesis of a variety of solid and
      hematologic cancers. Consequently, inhibition of STAT-mediated signaling has
      recently been proposed as a potential new therapeutic approach to the treatment
      of cancers. Having shown previously that the pan-cyclin-dependent kinase
      inhibitor flavopiridol binds to DNA and seems to kill cancer cells via that
      process in some circumstances, we evaluated the hypothesis that flavopiridol
      might consequently disrupt STAT3/DNA interactions, attenuate STAT3-directed
      transcription, and down-regulate STAT3 downstream polypeptides, including the
      antiapoptotic polypeptide Mcl-1. SDS-PAGE/immunoblotting and reverse
      transcription-PCR were used to assess RNA and polypeptide levels, respectively.
      DNA cellulose affinity chromatography and a nuclear elution assay were used to
      evaluate the ability of flavopiridol to disrupt STAT3/DNA interactions. A STAT3
      luciferase reporter assay was used to examine the ability of flavopiridol to
      attenuate STAT3-directed transcription. Colony-forming assays were used to assess
      cytotoxic synergy between flavopiridol and AG490. Flavopiridol was found to (a)
      disrupt STAT3/DNA interactions (DNA cellulose affinity chromatography and nuclear
      elution assay), (b) attenuate STAT3-directed transcription (STAT3 luciferase
      reporter assay), and (c) down-regulate the STAT3 downstream antiapoptotic
      polypeptide Mcl-1 at the transcriptional level (reverse transcription-PCR and SDS
      PAGE/immunoblotting). Furthermore, flavopiridol, but not the microtubule
      inhibitor paclitaxel, could be combined with the STAT3 pathway inhibitor AG490 to
      achieve cytotoxic synergy in A549 human non-small cell lung cancer cells.
      Collectively, these data suggest that flavopiridol can attenuate STAT3-directed
      transcription in a targeted fashion and may therefore be exploitable clinically
      in the development of chemotherapy regimens combining flavopiridol and other
      inhibitors of STAT3 signaling pathways.

PMID- 16432173
TI  - Antitumor efficacy of CD137 ligation is maximized by the use of a CD137 single
      chain Fv-expressing whole-cell tumor vaccine compared with CD137-specific
      monoclonal antibody infusion.
AB  - Tumor-destructive immune responses can be generated by engaging CD137 (4-1BB) via
      infusing a monoclonal antibody specific for CD137 or vaccinating with a single
      chain Fv (scFv) CD137-expressing whole-cell tumor vaccine. We assessed whether
      such a vaccine can induce tumor rejection in the neu-transgenic (neu-Tg) mouse
      breast cancer model and compared the antitumor efficacy of vaccination with the
      infusion of a CD137-specific antibody. Mammary carcinoma cells (MMC) from a neu
      Tg mouse were transfected to stably express surface scFv derived from the anti
      CD137 rat hybridoma 1D8 or 3H3. The anti-CD137 scFv-expressing cells were
      rejected when transplanted into neu-Tg mice by a mechanism that involved both
      CD4(+) and CD8(+) T cells, and vaccination with such cells delayed the outgrowth
      of MMC cells transplanted 3 days previously. T cells from neu-Tg mice that had
      been vaccinated proliferated and produced IFN-gamma when stimulated by MMC but
      not by antigen-negative variant breast cancer cells that did not express the neu
      tumor antigen. In addition, antibodies binding to the MMC but not to antigen
      negative variant cells were detected in sera from some but not all of the
      immunized mice. Complete regression of s.c. transplanted MMC tumors was observed
      in mice repeatedly immunized against MMC-1D8 starting on the day the MMC cells
      were transplanted. In contrast, repeated administration of either of two
      different anti-CD137 monoclonal antibodies did not induce complete tumor
      regression, although tumor growth was delayed.

PMID- 16432175
TI  - Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell
      proliferation in vitro and sensitize tumors to doxorubicin in vivo.
AB  - The activity and stability of the p53 tumor suppressor are regulated by the human
      homologue of the mouse double minute 2 (Hdm2) oncoprotein. It has been
      hypothesized that small molecules disrupting the Hdm2:p53 complex would allow for
      the activation of p53 and result in growth suppression. We have identified small
      molecule inhibitors of the Hdm2:p53 interaction using our proprietary ThermoFluor
      microcalorimetry technology. Medicinal chemistry and structure-based drug design
      led to the development of an optimized series of benzodiazepinediones, including
      TDP521252 and TDP665759. Activities were dependent on the expression of wild-type
      (wt) p53 and Hdm2 as determined by lack of potency in mutant or null p53
      expressing cell lines or cells engineered to no longer express Hdm2 and wt p53.
      TDP521252 and TDP665759 inhibited the proliferation of wt p53-expressing cell
      lines with average IC(50)s of 14 and 0.7 micromol/L, respectively. These results
      correlated with the direct cellular dissociation of Hdm2 from wt p53 observed
      within 15 minutes in JAR choriocarcinoma cells. Additional activities of these
      inhibitors in vitro include stabilization of p53 protein levels, up-regulation of
      p53 target genes in a DNA damage-independent manner, and induction of apoptosis
      in HepG2 cells. Administration of TDP665759 to mice led to an increase in
      p21(waf1/cip1) levels in liver samples. Finally, TDP665759 synergizes with
      doxorubicin both in culture and in an A375 xenograft model to decrease tumor
      growth. Taken together, these data support the potential utility of small
      molecule inhibitors of the Hdm2:p53 interaction for the treatment of wt p53
      expressing tumors.

PMID- 16432174
TI  - Enhanced antiproliferative effects of alkoxyalkyl esters of cidofovir in human
      cervical cancer cells in vitro.
AB  - Nearly all cervical cancers are associated with the high-risk subtypes of human
      papillomavirus (HPV) expressing the E6 and E7 oncoproteins. The E6 and E7
      oncoproteins reduce cellular levels of the p53 and the retinoblastoma (pRb) tumor
      suppressors, respectively, and represent an important component of the malignant
      phenotype. Several groups have shown that treatment with cidofovir suppresses
      levels of E6 and E7, restoring cellular p53 and pRb levels, in turn slowing cell
      replication and increasing the susceptibility of the cancer cells to radiation
      and apoptosis. Recently, our group synthesized alkoxyalkyl esters of cidofovir,
      which were found to be >100 times more active than unmodified cidofovir in vitro
      against various double-stranded DNA viruses, including cytomegalovirus, herpes
      simplex virus, adenoviruses, cowpox, vaccinia, and variola viruses. We compared
      the activity of octadecyloxyethyl-cidofovir (ODE-CDV) and oleyloxyethyl-cidofovir
      (OLE-CDV) with that of unmodified cidofovir against both HPV-negative and HPV
      positive cervical cancer cells. We compared the antiproliferation activity in
      CaSki, HeLa, and Me-180 cells, prototypical HPV-positive cell lines bearing the
      HPV-16, HPV-18, and HPV-68 high-risk subtypes, with the activity in C33A cells, a
      cervical cancer cell line lacking HPV, and in nonmalignant primary human foreskin
      fibroblast cells. OLE-CDV and ODE-CDV were several logs more potent than
      cidofovir in CaSki, Me-180, HeLa, and C33A cervical cancer cells as determined by
      2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner
      salt proliferation assay. Cell cycle analysis indicates that the cidofovir
      analogues interfere with passage of dividing cells through the S phase. ODE-CDV
      and OLE-CDV were 500 to 17,000 times more active than cidofovir in inhibiting the
      growth of cervical cancer cells. ODE-CDV and OLE-CDV showed selectivity for
      cervical cancer cells versus nonmalignant human foreskin fibroblast cells and
      warrant further investigation as potential therapies for cervical cancer.

PMID- 16432176
TI  - Sensitization of TRAIL-resistant cells by inhibition of heat shock protein 90
      with low-dose geldanamycin.
AB  - Due to its specificity and effectiveness, tumor necrosis factor-alpha-related
      apoptosis-inducing ligand (TRAIL) is being tested for cancer therapy. Inhibition
      of the function of heat shock protein 90 (HSP90) is under clinical trials for
      cancer therapy. However, some cancer cells are resistant to TRAIL, and at the
      dose required for inducing apoptosis, geldanamycin, a drug that inhibits HSP90
      function, has shown adverse effects. Therefore, our working plan was to identify
      a sublethal dose of geldanamycin and combine it with TRAIL to induce apoptosis in
      TRAIL-resistant prostate cancer cells. Treatment of LNCaP with 250 nmol/L
      geldanamycin inhibited HSP90 function but did not induce significant apoptosis.
      However, combination of geldanamycin and TRAIL induced highly significant
      apoptosis in TRAIL-resistant LNCaP cells. In addition to inducing caspase
      activity and apoptosis, treatment with geldanamycin and TRAIL decreased inhibitor
      of kappaB (IkappaB) kinase (IKK) complex proteins, IKKalpha, IKKbeta, and
      IKKgamma. The loss of IKK affected IkappaBalpha/nuclear factor-kappaB (NF-kappaB)
      interaction and reduced nuclear transport of NF-kappaB, resulting in reduced NF
      kappaB activity. Our data show increase in apoptosis using low, suboptimal dose
      of geldanamycin when used with TRAIL. These results provide a means to alleviate
      two problems: resistance to TRAIL and adverse effects of high-dose geldanamycin.

PMID- 16432177
TI  - Silencing of survivin gene by small interfering RNAs produces supra-additive
      growth suppression in combination with 17-allylamino-17-demethoxygeldanamycin in
      human prostate cancer cells.
AB  - Survivin is an antiapoptotic gene, which is overexpressed in most human tumors
      and involved in mitotic checkpoint control. Recent evidence points to an
      essential role for heat shock protein 90 (Hsp90) in survivin function regulation.
      Although the survivin-Hsp90 association may promote tumor cell proliferation, it
      may also suggest new opportunities for the design of novel anticancer approaches.
      We evaluated the effect of small interfering RNA (siRNA)-mediated inhibition of
      survivin on the proliferative potential of prostate cancer cells and their
      sensitivity to the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17
      AAG). Human androgen-independent prostate cancer cell lines (DU145 and PC-3) were
      transfected with four 21-mer double-stranded siRNAs (100 nmol/L) directed against
      different portions of survivin mRNA. After transfection, cells were collected and
      analyzed for survivin mRNA and protein expression, cell proliferation rate,
      ability to undergo apoptosis, and sensitivity to 17-AAG. Transfection of prostate
      cancer cells with siRNAs induced a variable extent of inhibition of survivin mRNA
      expression (39-60% compared with controls), which was paralleled by a 38% to 75%
      reduction in survivin protein abundance. The three siRNAs able to induce the
      greatest inhibition of survivin expression also significantly reduced cell
      proliferation and enhanced the rate of apoptosis, with a concomitant increase in
      caspase-9 activity. Sequential treatment with siRNA and 17-AAG induced supra
      additive antiproliferative effects in all cell lines, with an enhanced caspase-9
      dependent apoptotic response. These findings suggest that combined strategies
      aimed at interfering with the survivin-Hsp90 connection may provide novel
      approaches for treatment of androgen-independent prostate cancer.

PMID- 16432178
TI  - Identification of magnetic resonance detectable metabolic changes associated with
      inhibition of phosphoinositide 3-kinase signaling in human breast cancer cells.
AB  - Phosphoinositide 3-kinase (PI3K) is an attractive target for novel mechanism
      based anticancer treatment. We used magnetic resonance (MR) spectroscopy (MRS) to
      detect biomarkers of PI3K signaling inhibition in human breast cancer cells. MDA
      MB-231, MCF-7, and Hs578T cells were treated with the prototype PI3K inhibitor
      LY294002, and the (31)P MR spectra of cell extracts were monitored. In every
      case, LY294002 treatment was associated with a significant decrease in
      phosphocholine levels by up to 2-fold (P < 0.05). In addition, a significant
      increase in glycerophosphocholine levels by up to 5-fold was also observed (P
      <or= 0.05), whereas the content of glycerophosphoethanolamine, when detectable,
      did not change significantly. Nucleotide triphosphate levels did not change
      significantly in MCF-7 and MDA-MB-231 cells but decreased by approximately 1.3
      fold in Hs578T cells (P = 0.01). The changes in phosphocholine and
      glycerophosphocholine levels seen in cell extracts were also detectable in the
      (31)P MR spectra of intact MDA-MB-231 cells following exposure to LY294002. When
      treated with another PI3K inhibitor, wortmannin, MDA-MB-231 cells also showed a
      significant decrease in phosphocholine content by approximately 1.25-fold
      relative to the control (P < 0.05), whereas the levels of the remaining
      metabolites did not change significantly. Our results indicate that PI3K
      inhibition in human breast cancer cells by LY294002 and wortmannin is associated
      with a decrease in phosphocholine levels.

PMID- 16432179
TI  - Cancer-specific mutations in PIK3CA are oncogenic in vivo.
AB  - The PIK3CA gene, coding for the catalytic subunit p110alpha of class IA
      phosphatidylinositol 3-kinases (PI3Ks), is frequently mutated in human cancer.
      Mutated p110alpha proteins show a gain of enzymatic function in vitro and are
      oncogenic in cell culture. Here, we show that three prevalent mutants of
      p110alpha, E542K, E545K, and H1047R, are oncogenic in vivo. They induce tumors in
      the chorioallantoic membrane of the chicken embryo and cause hemangiosarcomas in
      the animal. These tumors are marked by increased angiogenesis and an activation
      of the Akt pathway. The target of rapamycin inhibitor RAD001 blocks tumor growth
      induced by the H1047R p110alpha mutant. The in vivo oncogenicity of PIK3CA
      mutants in an avian species strongly suggests a critical role for these mutated
      proteins in human malignancies.

PMID- 16432181
TI  - Defective cerebellar response to mitogenic Hedgehog signaling in Down [corrected]
      syndrome mice.
AB  - Trisomy 21 is the cause of Down [corrected] syndrome (DS) which is characterized
      by a number of phenotypes, including a brain which is small and hypocellular
      compared to that of euploid individuals. The cerebellum is disproportionately
      reduced. Ts65Dn mice are trisomic for orthologs of about half of the genes on
      human chromosome 21 and provide a genetic model for DS. These mice display a
      number of developmental anomalies analogous to those in DS, including a small
      cerebellum with a significantly decreased number of both granule and Purkinje
      cell neurons. Here we trace the origin of the granule cell deficit to precursors
      in early postnatal development, which show a substantially reduced mitogenic
      response to Hedgehog protein signaling. Purified cultures of trisomic granule
      cell precursors show a reduced but dose-dependent response to the Sonic hedgehog
      protein signal in vitro, demonstrating that this is a cell-autonomous deficit.
      Systemic treatment of newborn trisomic mice with a small molecule agonist of
      Hedgehog pathway activity increases mitosis and restores granule cell precursor
      populations in vivo. These results demonstrate a basis for and a potential
      therapeutic approach to a fundamental aspect of CNS pathology in DS.

PMID- 16432182
TI  - Teaching an old dog new tricks: SINEs of canine genomic diversity.

PMID- 16432180
TI  - Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of
      class I phosphoinositide 3-kinase.
AB  - Class I phosphoinositide 3-kinase contains four isoforms of the catalytic
      subunit, p110alpha, -beta, -gamma, and -delta. At physiological levels of
      expression, the wild-type p110alpha isoform lacks oncogenic potential, but gain
      of-function mutations and overexpression of p110alpha are correlated with
      oncogenicity. The p110beta, -gamma, and -delta isoforms induce transformation of
      cultured cells as wild-type proteins. This oncogenic potential requires kinase
      activity and can be suppressed by the target of rapamycin inhibitor rapamycin.
      The p110delta isoform constitutively activates the Akt signaling pathway;
      p110gamma activates Akt only in the presence of serum. The isoforms differ in
      their requirements for upstream signaling. The transforming activity of the
      p110gamma isoform depends on rat sarcoma viral oncogene homolog (Ras) binding;
      preliminary data suggest the same for p110beta and indicate Ras-independent
      oncogenic potential of p110delta. The surprising oncogenic potential of the wild
      type non-alpha isoforms of class I phosphoinositide 3-kinase may explain the
      dearth of cancer-specific mutations in these proteins, because these non-alpha
      isoforms could contribute to the oncogenic phenotype of the cell by differential
      expression.

PMID- 16432183
TI  - Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in
      vivo.
AB  - Neurons and glia are thought to arise from multipotent and self-renewing stem
      cells, which comprise the majority of neuroepithelial cells in the ventricular
      zone (VZ) of the early embryonic CNS. However, this idea remains to be tested
      rigorously, because CNS stem cells have been identified only by using in vitro
      assays, from which their abundance in vivo cannot be directly inferred. In the
      hematopoietic system, stem cells are characterized by using prospective isolation
      and direct in vivo transplantation. Here we have used this approach to ask
      whether most VZ progenitors behave as stem cells in vivo. The best-studied region
      of the embryonic CNS for addressing this problem is, arguably, the ventral spinal
      cord, within which progenitors in the motoneuron progenitor (pMN) domain
      sequentially generate motoneurons (MNs) and oligodendrocyte precursors (OPs).
      Virtually all VZ cells in pMN express the transcription factor Olig2. If most of
      these cells are stem cells, then they should maintain neurogenic potential, even
      at later, gliogenic stages. To test this hypothesis, we have prospectively
      isolated Olig2(+) cells from murine embryonic day (E)9.5 and E13.5 spinal cord
      and directly transplanted them to E2 chick spinal cord. Transplanted E9.5 cells
      generate both neurons, including MNs and OPs, whereas E13.5 cells generate. The
      observation that most Olig2(+) progenitors do not maintain neurogenic potential
      into the period of gliogenesis argues that they do not self-renew. These results
      do not support the commonly held view that most neuroepithelial cells in the
      embryonic CNS VZ are stem cells in vivo.

PMID- 16432184
TI  - Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia.
AB  - Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding
      the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13
      week delay, conditionally deleted (PU.1(-/-)) mice began dying of myeloid
      leukemia, and 95% of the mice surviving from early postinduction death developed
      transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr
      1 positive. The leukemic cells formed autonomous colonies in semisolid culture
      with varying clonal efficiency, but colony formation was enhanced by IL-3 and
      sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors
      analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage
      colony-stimulating factor production, and there was evidence of rearrangement of
      the IL-3 gene. Acquisition of autocrine growth-factor production and autonomous
      growth appeared to be major events in the transformation of conditionally deleted
      PU.1(-/-) cells to fully developed myeloid leukemic populations.

PMID- 16432185
TI  - In vivo identification of ribonucleoprotein-RNA interactions.
AB  - To understand the role of RNA-binding proteins (RBPs) in the regulation of gene
      expression, methods are needed for the in vivo identification of RNA-protein
      interactions. We have developed the peptide nucleic acid (PNA)-assisted
      identification of RBP technology to enable the identification of proteins that
      complex with a target RNA in vivo. Specific regions of the 3' and 5' UTRs of
      ankylosis mRNA were targeted by antisense PNAs transported into cortical neurons
      by the cell-penetrating peptide transportan 10. An array of proteins was isolated
      in complex with or near the targeted regions of the ankylosis mRNA through UV
      induced crosslinking of the annealed PNA-RNA-RBP complex. The first evidence for
      pharmacological modulation of these specific protein-RNA associations was
      observed. These data show that the PNA-assisted identification of the RBP
      technique is a reliable method to rapidly identify proteins interacting in vivo
      with the target RNA.

PMID- 16432186
TI  - Role of beta-arrestin 1 in the metastatic progression of colorectal cancer.
AB  - G protein-coupled receptor ligand-dependent transactivation of growth factor
      receptors has been implicated in human cancer cell proliferation, migration, and
      cell survival. For example, prostaglandin E(2) (PGE(2))-induced transactivation
      of the EGF receptor (EGFR) in colorectal carcinoma cells is mediated by means of
      a c-Src-dependent mechanism and regulates cell proliferation and migration.
      Recent evidence indicates that beta-arrestin 1 may act as an important mediator
      in G protein-coupled receptor-induced activation of c-Src. Whether beta-arrestin
      1 serves a functional role in these events is, however, unknown. We investigated
      the effects of PGE(2) on colorectal cancer cells expressing WT and mutant beta
      arrestin 1. Here we report that PGE(2) induces the association of a prostaglandin
      E receptor 4/beta-arrestin 1/c-Src signaling complex resulting in the
      transactivation of the EGFR and downstream Akt (PKB) signaling. The interaction
      of beta-arrestin 1 and c-Src is critical for the regulation of colorectal
      carcinoma cell migration in vitro as well as metastatic spread of disease to the
      liver in vivo. These results show that the prostaglandin E/beta-arrestin 1/c-Src
      signaling complex is a crucial step in PGE(2)-mediated transactivation of the
      EGFR and may play a pivotal role in tumor metastasis. Furthermore, our data
      implicate a functional role for beta-arrestin 1 as a mediator of cellular
      migration and metastasis.

PMID- 16432187
TI  - Climate change, body size evolution, and Cope's Rule in deep-sea ostracodes.
AB  - Causes of macroevolutionary trends in body size, such as Cope's Rule, the
      tendency of body size to increase over time, remain poorly understood. We used
      size measurements from Cenozoic populations of the ostracode genus
      Poseidonamicus, in conjunction with phylogeny and paleotemperature estimates, to
      show that climatic cooling leads to significant increases in body size, both
      overall and within individual lineages. The magnitude of size increase due to
      Cenozoic cooling is consistent with temperature-size relationships in
      geographically separated modern populations (Bergmann's Rule). Thus population
      level phenotypic evolution in response to climate change can be an important
      determinant of macroevolutionary trends in body size.

PMID- 16432188
TI  - A mutation in the human phospholamban gene, deleting arginine 14, results in
      lethal, hereditary cardiomyopathy.
AB  - The sarcoplasmic reticulum Ca(2+)-cycling proteins are key regulators of cardiac
      contractility, and alterations in sarcoplasmic reticulum Ca(2+)-cycling
      properties have been shown to be causal of familial cardiomyopathies. Through
      genetic screening of dilated cardiomyopathy patients, we identified a previously
      uncharacterized deletion of arginine 14 (PLN-R14Del) in the coding region of the
      phospholamban (PLN) gene in a large family with hereditary heart failure. No
      homozygous individuals were identified. By middle age, heterozygous individuals
      developed left ventricular dilation, contractile dysfunction, and episodic
      ventricular arrhythmias, with overt heart failure in some cases. Transgenic mice
      overexpressing the mutant PLN-R14Del recapitulated human cardiomyopathy
      exhibiting similar histopathologic abnormalities and premature death.
      Coexpression of the normal and mutant-PLN in HEK-293 cells resulted in
      sarcoplasmic reticulum Ca(2+)-ATPase superinhibition. The dominant effect of the
      PLN-R14Del mutation could not be fully removed, even upon phosphorylation by
      protein kinase A. Thus, by chronic suppression of sarcoplasmic reticulum Ca(2+)
      ATPase activity, the nonreversible superinhibitory function of mutant PLN-R14Del
      may lead to inherited dilated cardiomyopathy and premature death in both humans
      and mice.

PMID- 16432189
TI  - Theory of the deuterium NMR of sterol-phospholipid membranes.
AB  - A general theoretical model is described for the NMR spectra of mixtures of
      sterols and deuterium-labeled phospholipids. In the case of homogeneous
      membranes, the average quadrupole splittings are determined by equilibria between
      lipids in cholesterol-phospholipid complexes and lipids not in complexes.
      Chemical exchange of lipids between those in the free state and those in the
      complex state affects the deuterium resonance line shapes. The lifetime of a
      phospholipid molecule in an ergosterol-dipalmitoylphosphatidylcholine complex is
      estimated to be of the order of 10(-5) s on the basis of the observed line
      broadenings. In the vicinity of a critical point of a cholesterol-phospholipid
      mixture, fluctuations in the concentration of complexes also can contribute to
      the deuterium nuclear resonance line broadening. At the critical point, the
      temperature derivative of the concentration of complexes is discontinuous. There
      is a corresponding jump in the calculated heat capacity as well as in the
      temperature derivative of the deuterium NMR first moment.

PMID- 16432190
TI  - Mitochondrial transfer between cells can rescue aerobic respiration.
AB  - Current theory indicates that mitochondria were obtained 1.5 billion years ago
      from an ancient prokaryote. The mitochondria provided the capacity for aerobic
      respiration, the creation of the eukaryotic cell, and eventually complex
      multicellular organisms. Recent reports have found that mitochondria play
      essential roles in aging and determining lifespan. A variety of heritable and
      acquired diseases are linked to mitochondrial dysfunction. We report here that
      mitochondria are more dynamic than previously considered: mitochondria or mtDNA
      can move between cells. The active transfer from adult stem cells and somatic
      cells can rescue aerobic respiration in mammalian cells with nonfunctional
      mitochondria.

PMID- 16432191
TI  - Carbon under extreme conditions: phase boundaries and electronic properties from
      first-principles theory.
AB  - At high pressure and temperature, the phase diagram of elemental carbon is poorly
      known. We present predictions of diamond and BC8 melting lines and their phase
      boundary in the solid phase, as obtained from first-principles calculations.
      Maxima are found in both melting lines, with a triple point located at
      approximately 850 GPa and approximately 7,400 K. Our results show that hot,
      compressed diamond is a semiconductor that undergoes metalization upon melting.
      In contrast, in the stability range of BC8, an insulator to metal transition is
      likely to occur in the solid phase. Close to the diamond/liquid and BC8/liquid
      boundaries, molten carbon is a low-coordinated metal retaining some covalent
      character in its bonding up to extreme pressures. Our results provide constraints
      on the carbon equation of state, which is of critical importance for devising
      models of Neptune, Uranus, and white dwarf stars, as well as of extrasolar carbon
      rich planets.

PMID- 16432192
TI  - A plausible model of phyllotaxis.
AB  - A striking phenomenon unique to the kingdom of plants is the regular arrangement
      of lateral organs around a central axis, known as phyllotaxis. Recent molecular
      genetic experiments indicate that active transport of the plant hormone auxin is
      the key process regulating phyllotaxis. A conceptual model based on these
      experiments, introduced by Reinhardt et al. [Reinhardt, D., Pesce, E. R.,
      Stieger, P., Mandel, T., Baltensperger, K., et al. (2003) Nature 426, 255-260],
      provides an intuitively plausible interpretation of the data, but raises
      questions of whether the proposed mechanism is, in fact, capable of producing the
      observed temporal and spatial patterns, is robust, can start de novo, and can
      account for phyllotactic transitions, such as the frequently observed transition
      from decussate to spiral phyllotaxis. To answer these questions, we created a
      computer simulation model based on data described previously or in this paper and
      reasonable hypotheses. The model reproduces, within the standard error, the
      divergence angles measured in Arabidopsis seedlings and the effects of selected
      experimental manipulations. It also reproduces distichous, decussate, and
      tricussate patterns. The model thus offers a plausible link between molecular
      mechanisms of morphogenesis and the geometry of phyllotaxis.

PMID- 16432193
TI  - Identification of target actin content and polymerization status as a mechanism
      of tumor resistance after cytolytic T lymphocyte pressure.
AB  - To investigate tumor resistance to T cell lysis, a resistant variant was selected
      after specific cytolytic T lymphocytes (CTL) selection pressure. Although the
      resistant variant triggered perforin and granzyme B transcription in specific
      CTLs, as well as their degranulation, it exhibited a dramatic resistance to
      cytotoxic T cell killing. It also displayed strong morphological changes with
      alterations of the actin cytoskeleton. Electron microscopy analysis revealed a
      loosen interaction between CTLs and the resistant variant despite the formation
      of apparently normal conjugates. Transcriptional profiling identified a gene
      expression signature that distinguished sensitive from resistant tumor targets.
      More notably, we found that actin-related genes ephrin-A1 and scinderin were
      overexpressed in resistant target. Silencing of these genes using RNA
      interference resulted in a restoration of normal cell morphology and a
      significant attenuation of variant resistance to CTL killing. Our present study
      shows that a shift in cytoskeletal organization can be used, by tumor cells, as a
      strategy to promote their resistance after CTL selection pressure.

PMID- 16432194
TI  - Coupling of cell migration with neurogenesis by proneural bHLH factors.
AB  - After cell birth, almost all neurons in the mammalian central nervous system
      migrate. It is unclear whether and how cell migration is coupled with
      neurogenesis. Here we report that proneural basic helix-loop-helix (bHLH)
      transcription factors not only initiate neuronal differentiation but also
      potentiate cell migration. Mechanistically, proneural bHLH factors regulate the
      expression of genes critically involved in migration, including down-regulation
      of RhoA small GTPase and up-regulation of doublecortin and p35, which, in turn,
      modulate the actin and microtubule cytoskeleton assembly and enable newly
      generated neurons to migrate. In addition, we report that several DNA-binding
      deficient proneural genes that fail to initiate neuronal differentiation still
      activate migration, whereas a different mutation of a proneural gene that causes
      a failure in initiating cell migration still leads to robust neuronal
      differentiation. Collectively, these data suggest that transcription programs for
      neurogenesis and migration are regulated by bHLH factors through partially
      distinct mechanisms.

PMID- 16432195
TI  - Linkage disequilibrium sharing and haplotype-tagged SNP portability between
      populations.
AB  - The discovery of the block-like structure of linkage disequilibrium (LD) in human
      populations holds the promise of delineating the etiology of common diseases.
      However, understanding the magnitude, mechanism, and utility of between
      population LD sharing is critical for future genome-wide association studies. In
      this study, substantial LD sharing between six non-African populations was
      observed, although much less between African-American and non-African, based on
      20,000 SNPs of chromosome 21. We also demonstrated the respective roles of
      recombination and demographic events in shaping LD sharing. Furthermore, we
      showed that the haplotype-tagged SNPs chosen from one population are portable to
      the others in East Asia. Therefore, we concluded that the magnitude of LD sharing
      between human populations justifies the use of representative populations for
      selecting haplotype-tagged SNPs in genome-wide association studies of complex
      diseases.

PMID- 16432196
TI  - The central region of HDM2 provides a second binding site for p53.
AB  - HDM2 is a negative regulator of p53 that inhibits its transcriptional activity
      and subjects it to degradation by an E3 ligase activity. The primary binding site
      for HDM2 on p53 is located in its N-terminal domain. A second site on the p53
      core domain (p53C) binds to an unidentified site in HDM2. We found that this site
      is in its acidic domain and part of the zinc finger domain by examining the
      interaction of full-length and domain constructs of p53 with the N-terminal
      region of HDM2 and peptide arrays derived from the full-length protein. NMR
      spectroscopy showed that peptides derived from this region of HDM2 bound to
      residues in the specific DNA-binding site of p53C. The peptides were displaced
      from the site by gadd45 sequence-specific DNA. Phosphorylation of single amino
      acids in the central domain of HDM2 did not abolish the interaction between the
      HDM2-derived peptides and p53C. We speculate that this second binding site helps
      in stabilizing the interaction between HDM2 and p53 during p53 degradation.

PMID- 16432197
TI  - The Kernel Energy Method: application to a tRNA.
AB  - The Kernel Energy Method (KEM) may be used to calculate quantum mechanical
      molecular energy by the use of several model chemistries. Simplification is
      obtained by mathematically breaking a large molecule into smaller parts, called
      kernels. The full molecule is reassembled from calculations carried out on the
      kernels. KEM is as yet untested for RNA, and such a test is the purpose here. The
      basic kernel for RNA is a nucleotide that in general may differ from those of
      DNA. RNA is a single strand rather than the double helix of DNA. KEM energy has
      been calculated for a tRNA, whose crystal structure is known, and which contains
      2,565 atoms. The energy is calculated to be E = -108,995.1668 (a.u.), in the
      Hartree-Fock approximation, using a limited basis. Interaction energies are found
      to be consistent with the hydrogen-bonding scheme previously found. In this
      paper, the range of biochemical molecules, susceptible of quantum studies by
      means of the KEM, have been broadened to include RNA.

PMID- 16432198
TI  - The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor
      of histone deacetylases.
AB  - The association of the histone deacetylase (HDAC) inhibitor valproate (VPA) with
      atypical antipsychotics has become a frequent treatment strategy for
      schizophrenia and bipolar disorder. Because the VPA doses administered are
      elevated, one cannot assume that the benefits of the VPA plus antipsychotic
      treatment are exclusively related to the covalent modifications of nucleosomal
      histone tails. We compared the actions of N-(2-aminophenyl)-4-[N-(pyridin-3-yl
      methoxycarbonyl)aminomethyl]benzamide derivative (MS-275), which is a potent HDAC
      inhibitor in vitro, with the actions of VPA for their ability to (i) increase the
      acetylated status of brain nucleosomal histone tail domains and (ii) to regulate
      brain histone-RELN and histone-GAD(67) promoter interactions. MS-275 increases
      the content of acetylhistone 3 (Ac-H3) in the frontal cortex. Whereas this
      response peaks after a s.c. injection of 15 micromol/kg, the increase in Ac-H3
      content in the hippocampus becomes significant only after an injection of 60
      micromol/kg, suggesting that MS-275 is 30- to 100-fold more potent than VPA in
      increasing Ac-H3 in these brain regions. In contrast to VPA, MS-275, in doses up
      to 120 micromol/kg, fails to increase Ac-H3 content in the striatum. Chromatin
      immunoprecipitation shows that MS-275 increases Ac-H3-RELN and Ac-H3-GAD(67)
      promoter interaction in the frontal cortex. These results suggest that MS-275 is
      a potent brain region-selective HDAC inhibitor. It is likely that, in addition to
      MS-275, other benzamide derivatives, such as sulpiride, are brain-region
      selective inhibitors of HDACs. Hence, some benzamide derivatives may express a
      greater efficacy than VPA as an adjunctive to antipsychotics in the treatment of
      epigenetically induced psychiatric disorders.

PMID- 16432199
TI  - Identification of a conserved bacterial protein secretion system in Vibrio
      cholerae using the Dictyostelium host model system.
AB  - The bacterium Vibrio cholerae, like other human pathogens that reside in
      environmental reservoirs, survives predation by unicellular eukaryotes. Strains
      of the O1 and O139 serogroups cause cholera, whereas non-O1/non-O139 strains
      cause human infections through poorly defined mechanisms. Using Dictyostelium
      discoideum as a model host, we have identified a virulence mechanism in a non
      O1/non-O139 V. cholerae strain that involves extracellular translocation of
      proteins that lack N-terminal hydrophobic leader sequences. Accordingly, we have
      named these genes "VAS" genes for virulence-associated secretion, and we propose
      that these genes encode a prototypic "type VI" secretion system. We show that vas
      genes are required for cytotoxicity of V. cholerae cells toward Dictyostelium
      amoebae and mammalian J774 macrophages by a contact-dependent mechanism. A large
      number of Gram-negative bacterial pathogens carry genes homologous to vas genes
      and potential effector proteins secreted by this pathway (i.e., hemolysin
      coregulated protein and VgrG). Mutations in vas homologs in other bacterial
      species have been reported to attenuate virulence in animals and cultured
      macrophages. Thus, the genes encoding the VAS-related, type VI secretion system
      likely play an important conserved function in microbial pathogenesis and
      represent an additional class of targets for vaccine and antimicrobial drug-based
      therapies.

PMID- 16432200
TI  - A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two
      distinct classes of promoters.
AB  - A striking feature of the human genome is the dearth of CpG dinucleotides (CpGs)
      interrupted occasionally by CpG islands (CGIs), regions with relatively high
      content of the dinucleotide. CGIs are generally associated with promoters; genes,
      whose promoters are especially rich in CpG sequences, tend to be expressed in
      most tissues. However, all working definitions of what constitutes a CGI rely on
      ad hoc thresholds. Here we adopt a direct and comprehensive survey to identify
      the locations of all CpGs in the human genome and find that promoters segregate
      naturally into two classes by CpG content. Seventy-two percent of promoters
      belong to the class with high CpG content (HCG), and 28% are in the class whose
      CpG content is characteristic of the overall genome (low CpG content). The
      enrichment of CpGs in the HCG class is symmetric and peaks around the core
      promoter. The broad-based expression of the HCG promoters is not a consequence of
      a correlation with CpG content because within the HCG class the breadth of
      expression is independent of the CpG content. The overall depletion of CpGs
      throughout the genome is thought to be a consequence of the methylation of some
      germ-line CpGs and their susceptibility to mutation. A comparison of the
      frequencies of inferred deamination mutations at CpG and GpC dinucleotides in the
      two classes of promoters using SNPs in human-chimpanzee sequence alignments shows
      that CpGs mutate at a lower frequency in the HCG promoters, suggesting that CpGs
      in the HCG class are hypomethylated in the germ line.

PMID- 16432201
TI  - Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell
      mobilization.
AB  - Here, we report that cytokine-induced (granulocyte colony-stimulating factor and
      IL-8) hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC)
      mobilization is completely inhibited after low-dose (0.5 Gy) total-body
      irradiation (TBI). Because neutrophil granular proteases are regulatory mediators
      in cytokine-induced HSC/HPC mobilization, we considered a possible role for
      protease inhibitors in the induction of HSC/HPC mobilization. Bone marrow (BM)
      extracellular extracts that were obtained from murine femurs after 0.5 Gy of TBI
      contained an inhibitor of elastase. Also, after low-dose TBI, both Serpina1 mRNA
      and protein concentrations were increased in BM extracts, compared with extracts
      that were obtained from controls. The inhibitory activity in BM extracts of
      irradiated mice was reversed by addition of an Ab directed against Serpina1. To
      further study a possible in vivo role of Serpina1 in HSC/HPC mobilization, we
      administered Serpina1 before IL-8 injection. This administration resulted in an
      almost complete inhibition of HSC/HPC mobilization, whereas heat-inactivated
      Serpina1 had no effect. These results indicate that low-dose TBI inhibits
      cytokine-induced HSC/HPC mobilization and induces Serpina1 in the BM. Because
      exogenous administration of Serpina1 inhibits mobilization, we propose that
      radiation-induced Serpina1 is responsible for the inhibition of HSC/HPC
      mobilization. Also, we hypothesize that cytokine-induced HSC/HPC mobilization is
      determined by a critical balance between serine proteases and serine protease
      inhibitors.

PMID- 16432202
TI  - Computer simulations reveal properties of the cell-cell signaling network at the
      shoot apex in Arabidopsis.
AB  - The active transport of the plant hormone auxin plays a major role in the
      initiation of organs at the shoot apex. Polar localized membrane proteins of the
      PIN1 family facilitate this transport, and recent observations suggest that auxin
      maxima created by these proteins are at the basis of organ initiation. This
      hypothesis is based on the visual, qualitative characterization of the complex
      distribution patterns of the PIN1 protein in Arabidopsis. To take these analyses
      further, we investigated the properties of the patterns using computational
      modeling. The simulations reveal previously undescribed properties of PIN1
      distribution. In particular, they suggest an important role for the meristem
      summit in the distribution of auxin. We confirm these predictions by further
      experimentation and propose a detailed model for the dynamics of auxin fluxes at
      the shoot apex.

PMID- 16432203
TI  - An early specific cell-cell interaction occurs in the production of beta-amyloid
      in cell cultures.
AB  - We have earlier proposed that a cell-cell interaction, mediated by the specific
      binding of molecules of the beta-amyloid precursor protein (beta-APP) on one cell
      surface with molecules of presenilin (PS) on the other cell surface, is a
      required initial step in the ultimate production of beta-amyloid (Abeta) from
      beta-APP. Abeta is widely believed to be the neurotoxic agent in Alzheimer's
      disease. In this paper, we test this proposal by modifying cells to express
      surface beta-APP but no PS, and other cells to express surface PS but no beta
      APP. Coculturing these two cell populations at appropriate cell densities
      produces substantial amounts of Abeta that appear both in cell extracts and
      culture media. Such Abeta production could occur only if the two cell types
      interacted with one another to provide the beta-APP and the PS required for the
      generation of Abeta. The addition to the coculture, from the start, of the
      soluble specific N-terminal domain of the appropriate PS significantly reduces
      the amount of Abeta produced. These and related experiments, therefore, suggest a
      very different mechanism for Abeta production than the one that is currently
      widely accepted.

PMID- 16432204
TI  - Evidence that Perutz's double-beta-stranded subunit structure for beta-amyloids
      also applies to their channel-forming structures in membranes.
AB  - Although there is a growing body of evidence that different amyloidoses may have
      a similar molecular mechanism in common, the many details of this mechanism are
      not understood. In this study, we propose that there is a common molecular
      structure of the primary agents of these diseases, namely a small oligomer of
      Perutz's cylindrical double-beta-stranded subunit for polyglutamine and that this
      structure, which contains a central water-filled core, can spontaneously
      integrate into the bilayers of membranes to form aqueous pores. We suggest that
      this ability to produce permeable channels in appropriate neuronal membranes is a
      key element in the toxicity of the beta-amyloids. One strong criterion for the
      stability of the Perutz structure for an amyloid is that it contain approximately
      40 or more amino acid residues. We show here that the neurotoxic Abeta amyloids 1
      40 and 1-42, related to Alzheimer's disease, spontaneously enter the membranes of
      intact erythrocytes and cause their lysis but that Abeta 1-38 and Abeta 1-35,
      which are not neurotoxic, have no observable effects on erythrocytes, supporting
      our proposal. Other aspects of the proposed mechanism of cytotoxicity of the beta
      amyloids are explored.

PMID- 16432205
TI  - Metal stocks and sustainability.
AB  - The relative proportions of metal residing in ore in the lithosphere, in use in
      products providing services, and in waste deposits measure our progress from
      exclusive use of virgin ore toward full dependence on sustained use of recycled
      metal. In the U.S. at present, the copper contents of these three repositories
      are roughly equivalent, but metal in service continues to increase. Providing
      today's developed-country level of services for copper worldwide (as well as for
      zinc and, perhaps, platinum) would appear to require conversion of essentially
      all of the ore in the lithosphere to stock-in-use plus near-complete recycling of
      the metals from that point forward.

PMID- 16432206
TI  - Genomic fossils as a snapshot of the human transcriptome.
AB  - Processed pseudogenes (PPGs) are cDNA sequences that were generated through
      reverse transcription of mature, spliced mRNAs and have subsequently been
      reinserted at a new genomic location. These cDNA sequences are usually no longer
      transcribed and are considered "dead on arrival." Here we show that PPGs can be
      used to generate a map of the transcriptome. By analyzing thousands of human
      PPGs, we were able to discover hundreds of transcript variants so far
      unidentified. An experimental verification of a subset of these variants by RT
      PCR indicates that most of them are still active in the human transcriptome.
      Furthermore, we demonstrate that PPGs can enable the identification of ancient
      splice variants that were expressed ancestrally but are now extinct. Our results
      show that the genome itself carries a "virtual cDNA library" that can readily be
      used to analyze both present and ancestral transcripts. Our approach can be
      applied to sequenced metazoan genomes to computationally annotate splicing
      variation even when expressed sequences are unavailable.

PMID- 16432207
TI  - Autonomous artificial nanomotor powered by sunlight.
AB  - Light excitation powers the reversible shuttling movement of the ring component
      of a rotaxane between two stations located at a 1.3-nm distance on its dumbbell
      shaped component. The photoinduced shuttling movement, which occurs in solution,
      is based on a "four-stroke" synchronized sequence of electronic and nuclear
      processes. At room temperature the deactivation time of the high-energy charge
      transfer state obtained by light excitation is approximately 10 micros, and the
      time period required for the ring-displacement process is on the order of 100
      micros. The rotaxane behaves as an autonomous linear motor and operates with a
      quantum efficiency up to approximately 12%. The investigated system is a unique
      example of an artificial linear nanomotor because it gathers together the
      following features: (i) it is powered by visible light (e.g., sunlight); (ii) it
      exhibits autonomous behavior, like motor proteins; (iii) it does not generate
      waste products; (iv) its operation can rely only on intramolecular processes,
      allowing in principle operation at the single-molecule level; (v) it can be
      driven at a frequency of 1 kHz; (vi) it works in mild environmental conditions
      (i.e., fluid solution at ambient temperature); and (vii) it is stable for at
      least 10(3) cycles.

PMID- 16432208
TI  - Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus
      site is necessary for infection.
AB  - Papillomaviruses (PV) comprise a large family of nonenveloped DNA viruses that
      include the oncogenic PV types that are the causative agents of human cervical
      cancer. As is true of many animal DNA viruses, PV are taken into the cell by
      endocytosis and must escape from the endosomal compartment to the cytoplasm to
      initiate infection. Here we show that this step depends on the site-specific
      enzymatic cleavage of the PV minor virion protein L2 at a consensus furin
      recognition site. Cleavage by furin, a cell-encoded proprotein convertase, is
      known to be required for endosome escape by many bacterial toxins. However, to
      our knowledge, furin has not been previously implicated in the viral entry
      process. This step is potentially a target for PV inhibition.

PMID- 16432209
TI  - Real-time imaging of the somite segmentation clock: revelation of unstable
      oscillators in the individual presomitic mesoderm cells.
AB  - Notch signaling components such as the basic helix-loop-helix gene Hes1 are
      cyclically expressed by negative feedback in the presomitic mesoderm (PSM) and
      constitute the somite segmentation clock. Because Hes1 oscillation occurs in many
      cell types, this clock may regulate the timing in many biological systems.
      Although the Hes1 oscillator is stable in the PSM, it damps rapidly in other
      cells, suggesting that the oscillators in the former and the latter could be
      intrinsically different. Here, we have established the real-time bioluminescence
      imaging system of Hes1 expression and found that, although Hes1 oscillation is
      robust and stable in the PSM, it is unstable in the individual dissociated PSM
      cells, as in fibroblasts. Thus, the Hes1 oscillators in the individual PSM cells
      and fibroblasts are intrinsically similar, and these results, together with
      mathematical simulation, suggest that cell-cell communication is essential not
      only for synchronization but also for stabilization of cellular oscillators.

PMID- 16432211
TI  - Generalized multidimensional scaling: a framework for isometry-invariant partial
      surface matching.
AB  - An efficient algorithm for isometry-invariant matching of surfaces is presented.
      The key idea is computing the minimum-distortion mapping between two surfaces.
      For this purpose, we introduce the generalized multidimensional scaling, a
      computationally efficient continuous optimization algorithm for finding the least
      distortion embedding of one surface into another. The generalized
      multidimensional scaling algorithm allows for both full and partial surface
      matching. As an example, it is applied to the problem of expression-invariant
      three-dimensional face recognition.

PMID- 16432212
TI  - Nitric oxide regulates endocytosis by S-nitrosylation of dynamin.
AB  - The GTPase dynamin regulates endocytic vesicle budding from the plasma membrane,
      but the molecular mechanisms involved remain incompletely understood. We report
      that dynamin, which interacts with NO synthase, is S-nitrosylated at a single
      cysteine residue (C607) after stimulation of the beta(2) adrenergic receptor. S
      nitrosylation increases dynamin self-assembly and GTPase activity and facilitates
      its redistribution to the membrane. A mutant protein bearing a C607A substitution
      does not self-assemble properly or increase its enzymatic activity in response to
      NO. In NO-generating cells, expression of dynamin C607A, like the GTPase
      deficient dominant-negative K44A dynamin, inhibits both beta(2) adrenergic
      receptor internalization and bacterial invasion. Furthermore, exogenous or
      endogenously produced NO enhances internalization of both beta(2) adrenergic and
      epidermal growth factor receptors. Thus, NO regulates endocytic vesicle budding
      by S-nitrosylation of dynamin. Collectively, our data suggest a general NO
      dependent mechanism by which the trafficking of receptors may be regulated and
      raise the idea that pathogenic microbes and viruses may induce S-nitrosylation of
      dynamin to facilitate cellular entry.

PMID- 16432210
TI  - Genetic polymorphism and protein conformational plasticity in the calmodulin
      superfamily: two ways to promote multifunctionality.
AB  - Calcium signaling pathways control a variety of cellular events such as gene
      transcription, protein phosphorylation, nucleotide metabolism, and ion transport.
      These pathways often involve a large number of calcium-binding proteins
      collectively known as the calmodulin or EF-hand protein superfamily. Many EF-hand
      proteins undergo a large conformational change upon binding to Ca(2+) and target
      proteins. All members of the superfamily share marked sequence homology and
      similar structural features required to sense Ca(2+). Despite such structural
      similarities, the functional diversity of EF-hand calcium-binding proteins is
      extraordinary. Calmodulin itself can bind >300 different proteins, and the many
      members of the neuronal calcium sensor and S100 protein families collectively
      recognize a largely different set of target proteins. Recent biochemical and
      structural studies of many different EF-hand proteins highlight remarkable
      similarities and variations in conformational responses to the common ligand
      Ca(2+) and their respective cellular targets. In this review, we examine the
      essence of molecular recognition activities and the mechanisms by which
      calmodulin superfamily proteins control a wide variety of Ca(2+) signaling
      processes.

PMID- 16432213
TI  - Dissection of a viral autoprotease elucidates a function of a cellular chaperone
      in proteolysis.
AB  - Replication of positive-strand RNA viruses involves translation of polyproteins
      which are proteolytically processed into functional peptides. These maturation
      steps often involve virus-encoded autoproteases specialized in generating their
      own N or C termini. Nonstructural protein 2 (NS2) of the pestivirus bovine viral
      diarrhea virus represents such an enzyme. Bovine viral diarrhea virus NS2 creates
      in cis its own C terminus and thereby releases an essential viral replication
      factor. As a unique feature, this enzyme requires for proteolytic activity
      stoichiometric amounts of a cellular chaperone termed Jiv (J-domain protein
      interacting with viral protein) or its fragment Jiv90. To obtain insight into the
      structural organization of the NS2 autoprotease, the basis for its restriction to
      cis cleavage, as well as its activation by Jiv, we dissected NS2 into functional
      domains. Interestingly, an N-terminal NS2 fragment covering the active center of
      the protease, cleaved in trans an artificial substrate composed of a C-terminal
      NS2 fragment and two downstream amino acids. In the authentic NS2, the 4 C
      terminal amino acids interfered with binding and cleavage of substrates offered
      in trans. These findings strongly suggest an intramolecular product inhibition
      for the NS2 autoprotease. Remarkably, the chaperone fragment Jiv90 independently
      interacted with protease and substrate domain and turned out to be essential for
      the formation of a protease/substrate complex that is required for cleavage.
      Thus, the function of the cell-derived protease cofactor Jiv in proteolysis is
      regulation of protease/substrate interaction, which ultimately results in
      positioning of active site and substrate peptide into a cleavage-competent
      conformation.

PMID- 16432214
TI  - A SNP in the flt-1 promoter integrates the VEGF system into the p53
      transcriptional network.
AB  - The VEGF system is essential for angiogenesis. VEGF overexpression frequently
      correlates with increased microvascularity and metastasis and decreased
      spontaneous apoptosis. Although a precise mechanism has not been established,
      studies suggest that VEGF expression is negatively regulated by p53, a master
      regulator and tumor suppressor. There are no reports of additional components of
      the VEGF signal transduction pathway being part of the p53 transcriptional
      network. A target of VEGF, the VEGF receptor 1/flt-1, can regulate growth and
      migration of endothelial cells and modulate angiogenesis. VEGF appears to be up
      regulated in various cancers in which flt-1 may have a role in tumor progression
      and metastasis. We identified a C-to-T SNP upstream of the transcriptional start
      site in approximately 6% of the people examined. The SNP is located within a
      putative p53 response element. Only the promoter with the T SNP (FLT1-T) was
      responsive to p53 when examined with reporter assays or by endogenous gene
      expression analysis in cell lines with different SNP status. In response to
      doxorubicin-induced DNA damage, there was clear allele discrimination based on
      p53 binding at the FLT1-T but not FLT1-C promoters as well as p53-dependent
      induction of flt-1 mRNA, which required the presence of FLT1-T. Our results
      establish that p53 can differentially stimulate transcription at a polymorphic
      variant of the flt-1 promoter and directly places the VEGF system in the p53
      stress-response network via flt-1 in a significant fraction of the human
      population. We suggest that the p53-VEGF-flt-1 interaction is relevant to risks
      in angiogenesis-associated diseases, including cancer.

PMID- 16432215
TI  - Crystal structure of a core spliceosomal protein interface.
AB  - The precise excision of introns from precursor mRNAs (pre-mRNAs) in eukaryotes is
      accomplished by the spliceosome, a complex assembly containing five small nuclear
      ribonucleoprotein (snRNP) particles. Human p14, a component of the spliceosomal
      U2 and U11/U12 snRNPs, has been shown to associate directly with the pre-mRNA
      branch adenosine early in spliceosome assembly and within the fully assembled
      spliceosome. Here we report the 2.5-A crystal structure of a complex containing
      p14 and a peptide derived from the p14-associated U2 snRNP component SF3b155. p14
      contains an RNA recognition motif (RRM), the surface of which is largely occluded
      by a C-terminal alpha-helix and a portion of the SF3b155 peptide. An analysis of
      RNA.protein crosslinking to wild-type and mutant p14 shows that the branch
      adenosine directly interacts with a conserved aromatic within a pocket on the
      surface of the complex. This result, combined with a comparison of the structure
      with known RRMs and pseudoRRMs as well as model-building by using the electron
      cryomicroscopy structure of a spliceosomal U11/U12 di-snRNP, suggests that
      p14.SF3b155 presents a noncanonical surface for RNA recognition at the heart of
      the mammalian spliceosome.

PMID- 16432217
TI  - The structure of nucleosome assembly protein 1.
AB  - Nucleosome assembly protein 1 (NAP-1) is an integral component in the
      establishment, maintenance, and dynamics of eukaryotic chromatin. It shuttles
      histones into the nucleus, assembles nucleosomes, and promotes chromatin
      fluidity, thereby affecting the transcription of many genes. The 3.0 A crystal
      structure of yeast NAP-1 reveals a previously uncharacterized fold with
      implications for histone binding and shuttling. A long alpha-helix is responsible
      for homodimerization via a previously uncharacterized antiparallel non-coiled
      coil, and an alpha/beta domain is implicated in protein-protein interaction. A
      nuclear export sequence that is embedded in the dimerization helix is almost
      completely masked by an accessory domain that contains several target sites for
      casein kinase II. The four-stranded antiparallel beta-sheet that characterizes
      the alpha/beta domain is found in all histone chaperones, despite the absence of
      homology in sequence, structural context, or quaternary structure. To our
      knowledge, this is the first structure of a member of the large NAP family of
      proteins and suggests a mechanism by which the shuttling of histones to and from
      the nucleus is regulated.

PMID- 16432218
TI  - Torque-speed relationship of the bacterial flagellar motor.
AB  - Many swimming bacteria are propelled by flagellar filaments driven by a rotary
      motor. Each of these tiny motors can generate an impressive torque. The motor
      torque vs. speed relationship is considered one of the most important measurable
      characteristics of the motor and therefore is a major criterion for judging
      models proposed for the working mechanism. Here we give an explicit explanation
      for this torque-speed curve. The same physics also can explain certain puzzling
      properties of other motors.

PMID- 16432216
TI  - Human alpha-defensins block papillomavirus infection.
AB  - Sexually transmitted human papillomaviruses (HPVs) are the primary cause of
      cervical cancer. Recent advances in techniques for production of papillomaviral
      vectors [known as pseudoviruses (PsVs)] have made it possible to perform high
      throughput screens for compounds that might block the initial stages of
      papillomavirus infection. We have used PsVs to screen a variety of compounds that
      might function as inhibitors of HPV infection, with emphasis on human peptides
      previously implicated in innate antimicrobial immunity. Little is known about the
      possible activity of these peptides against nonenveloped viruses, such as HPVs.
      Our screen revealed that human alpha-defensins 1-3 [known as human neutrophil
      peptides (HNPs) 1-3] and human alpha-defensin 5 (HD-5) are potent antagonists of
      infection by both cutaneous and mucosal papillomavirus types. In contrast, human
      beta-defensins 1 and 2 displayed little or no anti-HPV activity. HD-5 was
      particularly active against sexually transmitted HPV types, with 50% inhibitory
      doses in the high ng/ml range. Microscopic studies of PsV inhibition by the alpha
      defensins revealed that they block virion escape from endocytic vesicles but not
      virion binding or internalization. Consistent with this finding, PsVs remained
      susceptible to inhibition by alpha-defensins for many hours after initial binding
      to cells. HNPs 1-3 and HD-5 have been reported to be present in the female
      genital tract at levels that overlap those that inhibit HPVs in vitro, suggesting
      that they could present a natural barrier to the sexual transmission of HPV and
      could serve as the basis of a broad-spectrum topical microbicide.

PMID- 16432219
TI  - Water and ligand entry in myoglobin: assessing the speed and extent of heme
      pocket hydration after CO photodissociation.
AB  - A previously undescribed spectrokinetic assay for the entry of water into the
      distal heme pocket of wild-type and mutant myoglobins is presented. Nanosecond
      photolysis difference spectra were measured in the visible bands of sperm whale
      myoglobin as a function of distal pocket mutation and temperature. A small blue
      shift in the 560-nm deoxy absorption peak marked water entry several hundred
      nanoseconds after CO photodissociation. The observed rate suggests that water
      entry is rate-limited by the escape of internal dissociated CO. The heme pocket
      hydration and geminate recombination yields were found to be the primary factors
      controlling the overall bimolecular association rate constants for CO binding to
      the mutants studied. The kinetic analysis provides estimates of 84%, 60%, 40%,
      0%, and 99% for the steady-state hydrations of wild-type, H64Q, H64A, H64L, and
      V68F deoxymyoglobin, respectively. The second-order rate constants for CO and
      H(2)O entry into the empty distal pocket of myoglobin are markedly different, 8 x
      10(7) and 2 x 10(5) M(-1).s(-1), respectively, suggesting that hydrophobic
      partitioning of the apolar gas from the aqueous phase into the relatively apolar
      protein interior lowers the free energy barrier for CO entry.

PMID- 16432220
TI  - A unique role of the DNA fragmentation factor in maintaining genomic stability.
AB  - DNA fragmentation is a hallmark of apoptosis (programmed cell death). However,
      the biological function of apoptotic DNA fragmentation remains unclear. Here, we
      show that DNA fragmentation factor plays an important role for maintaining
      genomic stability. Inhibition or loss of the DNA fragmentation factor
      (DFF)/caspase-activated DNase (CAD), whose nuclease activity is responsible for
      digesting genomic DNA during apoptosis, led to significant increases in
      spontaneous or induced gene mutations, gene amplifications, and chromosomal
      instability in primary mouse cells and transformed human cell lines. The
      mechanism underlying genetic instability in DFF/CAD-deficient cells, at least in
      part, involves a small but significant elevation in the survival of cells exposed
      to ionizing radiation, suggesting that apoptotic DNA fragmentation factor
      contributes to genomic stability by ensuring the removal of cells that have
      suffered DNA damage. In support of this hypothesis are the observations of
      increased cellular transformation of mouse embryonic cells from the DFF/CAD-null
      mice and significantly enhanced susceptibility to radiation-induced
      carcinogenesis in these mice. These data, in combination with published reports
      on the existence of tumor-specific gene mutations/deletions in the DFF/CAD genes
      in human cancer samples, suggest that apoptotic DNA fragmentation factor is
      required for the maintenance of genetic stability and may play a role in tumor
      suppression.

PMID- 16432221
TI  - Neural connections of the posteromedial cortex in the macaque.
AB  - The posterior cingulate and the medial parietal cortices constitute an ensemble
      known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29,
      30, 31, and 7m. To understand the neural relationship of the PMC with the rest of
      the brain, we injected its component areas with four different anterograde and
      retrograde tracers in the cynomolgus monkey and found that all PMC areas are
      interconnected with each other and with the anterior cingulate, the mid
      dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as
      the thalamus, where projections from some of the PMC areas traverse in an
      uninterrupted bar-like manner, the dorsum of this structure from the
      posteriormost nuclei to its rostralmost tip. All PMC regions also receive
      projections from the claustrum and the basal forebrain and project to the
      caudate, the basis pontis, and the zona incerta. Moreover, the posterior
      cingulate areas are interconnected with the parahippocampal regions, whereas the
      medial parietal cortex projects only sparsely to the presubiculum. Although local
      interconnections and shared remote connections of all PMC components suggest a
      functional relationship among them, the distinct connections of each area with
      different neural structures suggests that distinct functional modules may be
      operating within the PMC. Our study provides a large-scale map of the PMC
      connections with the rest of the brain, which may serve as a useful tool for
      future studies of this cortical region and may contribute to elucidating its
      intriguing pattern of activity seen in recent functional imaging studies.

PMID- 16432222
TI  - Accordion waves in Myxococcus xanthus.
AB  - Myxococcus xanthus are Gram-negative bacteria that glide on solid surfaces,
      periodically reversing their direction of movement. When starved, M. xanthus
      cells organize their movements into waves of cell density that sweep over the
      colony surface. These waves are unique: Although they appear to interpenetrate,
      they actually reflect off one another when they collide, so that each wave crest
      oscillates back and forth with no net displacement. Because the waves reflect the
      coordinated back and forth oscillations of the individual bacteria, we call them
      "accordion" waves. The spatial oscillations of individuals are a manifestation of
      an internal biochemical oscillator, probably involving the Frz chemosensory
      system. These internal "clocks," each of which is quite variable, are
      synchronized by collisions between individual cells using a contact-mediated
      signal-transduction system. The result of collision signaling is that the
      collective spatial behavior is much less variable than the individual
      oscillators. In this work, we present experimental observations in which
      individual cells marked with GFP can be followed in groups of unlabeled cells in
      monolayer cultures. These data, together with an agent-based computational model
      demonstrate that the only properties required to explain the ripple patterns are
      an asymmetric biochemical limit cycle that controls direction reversals and
      asymmetric contact-induced signaling between cells: Head-to-head signaling is
      stronger than head-to-tail signaling. Together, the experimental and
      computational data provide new insights into how populations of interacting
      oscillators can synchronize and organize spatially to produce morphogenetic
      patterns that may have parallels in higher organisms.

PMID- 16432224
TI  - A comprehensive description of the transcriptome of the
      hypothalamoneurohypophyseal system in euhydrated and dehydrated rats.
AB  - The hypothalamoneurohypophyseal system (HNS) consists of the large peptidergic
      magnocellular neurons of the supraoptic hypo thalamic nucleus (SON) and the
      paraventricular hypothalamic nucleus (PVN), the axons of which course through the
      internal zone of the median eminence and terminate at blood capillaries of the
      posterior lobe of the pituitary gland. The HNS is a specialized brain
      neurosecretory apparatus responsible for the production of the antidiuretic
      peptide hormone vasopressin (VP). VP maintains water balance by promoting water
      conservation at the level of the kidney. Dehydration evokes a massive increase in
      the regulated release of VP from magnocellular neuron axon terminals in the
      posterior pituitary, which is accompanied by a plethora of changes in the
      morphology, electrophysiological properties, and biosynthetic and secretory
      activity of the HNS. We wish to understand this functional plasticity in terms of
      the differential expression of genes. We have therefore used microarrays to
      comprehensively catalog the genes expressed in the PVN, the SON and the
      neurointermediate lobe of the pituitary gland of control and dehydrated rats.
      Comparison of these gene lists has enabled us to identify transcripts that are
      regulated as a consequence of dehydration as well as RNAs that are enriched in
      the PVN or the SON. We suggest that these differentially expressed genes
      represent candidate regulators and effectors of HNS activity and remodeling.

PMID- 16432223
TI  - Retroviral vector integration deregulates gene expression but has no consequence
      on the biology and function of transplanted T cells.
AB  - The use of retroviral vectors in gene therapy has raised safety concerns for the
      genotoxic risk associated with their uncontrolled insertion into the human
      genome. We have analyzed the consequences of retroviral transduction in T cells
      from leukemic patients treated with allogeneic stem cell transplantation and
      donor lymphocytes genetically modified with a suicide gene (HSV-TK). Retroviral
      vectors integrate preferentially within or near transcribed regions of the
      genome, with a preference for sequences around promoters and for genes active in
      T cells at the time of transduction. Quantitative transcript analysis shows that
      one fifth of these integrations affect the expression of nearby genes. However,
      transduced T cell populations maintain remarkably stable gene expression
      profiles, phenotype, biological functions, and immune repertoire in vivo, with no
      evidence of clonal selection up to 9 yr after administration. Analysis of
      integrated proviruses in transduced cells before and after transplantation
      indicates that integrations interfering with normal T cell function are more
      likely to lead to clonal ablation than expansion in vivo. Despite the potentially
      dangerous interactions with the T cell genome, retroviral integration has
      therefore little consequence on the safety and efficacy of T cell
      transplantation.

PMID- 16432225
TI  - Essential role of B-Raf in ERK activation during extraembryonic development.
AB  - The kinases of the Raf family have been intensively studied as activators of the
      mitogen-activated protein kinase kinase/extra-cellular signal-regulated kinase
      (ERK) module in regulated and deregulated proliferation. Genetic evidence that
      Raf is required for ERK activation in vivo has been obtained in lower organisms,
      which express only one Raf kinase, but was hitherto lacking in mammals, which
      express more than one Raf kinase. Ablation of the two best studied Raf kinases, B
      Raf and Raf-1, is lethal at midgestation in mice, hampering the detailed study of
      the essential functions of these proteins. Here, we have combined conventional
      and conditional gene ablation to show that B-Raf is essential for ERK activation
      and for vascular development in the placenta. B-Raf-deficient placentae show
      complete absence of phosphorylated ERK and strongly reduced HIF-1alpha and VEGF
      levels, whereas all these parameters are normal in Raf-1-deficient placentae. In
      addition, neither ERK phosphorylation nor development are affected in B-raf
      deficient embryos that are born alive obtained by epiblast-restricted gene
      inactivation. The data demonstrate that B-Raf plays a nonredundant role in ERK
      activation during extraembyronic mammalian development in vivo.

PMID- 16432226
TI  - Peptide motifs of the single dominantly expressed class I molecule explain the
      striking MHC-determined response to Rous sarcoma virus in chickens.
AB  - Compared with the MHC of typical mammals, the chicken MHC is smaller and simpler,
      with only two class I genes found in the B12 haplotype. We make five points to
      show that there is a single-dominantly expressed class I molecule that can have a
      strong effect on MHC function. First, we find only one cDNA for two MHC
      haplotypes (B14 and B15) and cDNAs corresponding to two genes for the other six
      (B2, B4, B6, B12, B19, and B21). Second, we find, for the B4, B12, and B15
      haplotypes, that one cDNA is at least 10-fold more abundant than the other.
      Third, we use 2D gel electrophoresis of class I molecules from pulse-labeled
      cells to show that there is only one heavy chain spot for the B4 and B15
      haplotypes, and one major spot for the B12 haplotype. Fourth, we determine the
      peptide motifs for B4, B12, and B15 cells in detail, including pool sequences and
      individual peptides, and show that the motifs are consistent with the peptides
      binding to models of the class I molecule encoded by the abundant cDNA. Finally,
      having shown for three haplotypes that there is a single dominantly expressed
      class I molecule at the level of RNA, protein, and antigenic peptide, we show
      that the motifs can explain the striking MHC-determined resistance and
      susceptibility to Rous sarcoma virus. These results are consistent with the
      concept of a "minimal essential MHC" for chickens, in strong contrast to typical
      mammals.

PMID- 16432228
TI  - Mulberry latex rich in antidiabetic sugar-mimic alkaloids forces dieting on
      caterpillars.
AB  - Since ancient times, mulberry leaves (Morus spp.) have been used to rear the
      silkworm Bombyx mori. Because the silkworm grows well on mulberry leaves, the
      toxicities and defensive activities of these leaves against herbivorous insects
      have been overlooked. Here we show that mulberry leaves are highly toxic to
      caterpillars other than the silkworm B. mori, because of the ingredients of the
      latex, a milky sap exuded from mulberry leaf veins. The toxicity of mulberry
      leaves was lost when the latex was eliminated from the leaves, and artificial
      diets containing latex showed toxicity. Mulberry latex contained very high
      concentrations of alkaloidal sugar-mimic glycosidase inhibitors reported to have
      antidiabetic activities, such as 1,4-dideoxy-1,4-imino-D-arabinitol, 1
      deoxynojirimycin, and 1,4-dideoxy-1,4-imino-D-ribitol. The overall concentrations
      of these inhibitors in latex reached 1.5-2.5% (8-18% dry weight) in several
      mulberry varieties, which were approximately 100 times the concentrations
      previously reported from whole mulberry leaves. These sugar-mimic alkaloids were
      toxic to caterpillars but not to the silkworm B. mori, indicating that the
      silkworm can circumvent the mulberry tree's defense. Our results suggest that
      latex ingredients play key roles in defense of this tree and of other plants
      against insect herbivory, and they imply that plant latexes are treasuries of
      bioactive substances useful as medicines and pesticides.

PMID- 16432229
TI  - Active digestion of sperm mitochondrial DNA in single living sperm revealed by
      optical tweezers.
AB  - In almost all eukaryotes, mitochondrial (mt) genes are transmitted to progeny
      mainly from the maternal parent. The most popular explanation for this phenomenon
      is simple dilution of paternal mtDNA, because the paternal gametes (sperm) are
      much smaller than maternal gametes (egg) and contribute a limited amount of
      mitochondria to the progeny. Recently, this simple explanation has been
      challenged in several reports that describe the active digestion of sperm mtDNA,
      down-regulation of mtDNA replication in sperm, and proteolysis of mitochondria
      triggered by ubiquitination. In this investigation, we visualized mt nucleoids in
      living sperm by using highly sensitive SYBR green I vital staining. The ability
      to visualize mt nucleoids allowed us to clarify that the elimination of sperm
      mtDNA upon fertilization is achieved through two steps: (i) gradual decrease of
      mt nucleoid numbers during spermatogenesis and (ii) rapid digestion of sperm
      mtDNA just after fertilization. One notable point is that the digestion of mtDNA
      is achieved before the complete destruction of mitochondrial structures, which
      may be necessary to avoid the diffusion and transmission of potentially
      deleterious sperm mtDNA to the progeny.

PMID- 16432227
TI  - ATM promotes apoptosis and suppresses tumorigenesis in response to Myc.
AB  - Overexpression of the c-myc oncogene contributes to the development of a
      significant number of human cancers. In response to deregulated Myc activity, the
      p53 tumor suppressor is activated to promote apoptosis and inhibit tumor
      formation. Here we demonstrate that p53 induction in response to Myc
      overexpression requires the ataxia-telangiectasia mutated (ATM) kinase, a major
      regulator of the cellular response to DNA double-strand breaks. In a transgenic
      mouse model overexpressing Myc in squamous epithelial tissues, inactivation of
      Atm suppresses apoptosis and accelerates tumorigenesis. Deregulated Myc
      expression induces DNA damage in primary transgenic keratinocytes and the
      formation of gammaH2AX and phospho-SMC1 foci in transgenic tissue. These findings
      suggest that Myc overexpression causes DNA damage in vivo and that the ATM
      dependent response to this damage is critical for p53 activation, apoptosis, and
      the suppression of tumor development.

PMID- 16432230
TI  - Tumor marker-responsive behavior of gels prepared by biomolecular imprinting.
AB  - We report dynamic glycoprotein recognition of gels prepared by biomolecular
      imprinting using lectin and antibody molecules as ligands for tumor-specific
      marker glycoproteins. The glycoprotein-imprinted gels prepared with minute
      amounts of cross-linkers could dynamically recognize tumor-specific marker
      glycoproteins by lectin and antibody ligands and induce volume changes according
      to the glycoprotein concentration. The glycoprotein-imprinted gel shrank in
      response to a target glycoprotein but nonimprinted gel swelled a little. The
      glycoprotein-responsive shrinking of the imprinted gel was caused by formation of
      lectin-glycoprotein-antibody complexes that acted as reversible cross-linking
      points. Glycoprotein-imprinted gels only shrank when both lectin and antibody in
      the gels simultaneously recognized the saccharide and peptide chains of the
      target glycoprotein. As shrinking behavior of biomolecularly imprinted gels in
      response to glycoproteins enables the accurate detection and recognition of tumor
      specific marker glycoproteins, they have many potential applications as smart
      devices in sensing systems and for molecular diagnostics.

PMID- 16432231
TI  - Intercellular coupling amplifies fate segregation during Caenorhabditis elegans
      vulval development.
AB  - During vulval development in Caenorhabditis elegans, six precursor cells acquire
      a spatial pattern of distinct cell fates. This process is guided by a gradient in
      the soluble factor, LIN-3, and by direct interactions between neighboring cells
      mediated by the Notch-like receptor, LIN-12. Genetic evidence has revealed that
      these two extracellular signals are coupled: lateral cell-cell interactions
      inhibit LIN-3-mediated signaling, whereas LIN-3 regulates the extent of lateral
      signaling. To elucidate the quantitative implications of this coupled network
      topology for cell patterning during vulval development, we developed a
      mathematical model of LIN-3/LIN-12-mediated signaling in the vulval precursor
      cell array. Our analysis reveals that coupling LIN-3 and LIN-12 amplifies
      cellular perception of the LIN-3 gradient and polarizes lateral signaling, both
      of which enhance fate segregation beyond that achievable by an uncoupled system.

PMID- 16432233
TI  - Variable molecular clocks in hominoids.
AB  - Generation time is an important determinant of a neutral molecular clock. There
      are several human-specific life history traits that led to a substantially longer
      generation time in humans than in other hominoids. Indeed, a long generation time
      is considered an important trait that distinguishes humans from their closest
      relatives. Therefore, humans may exhibit a significantly slower molecular clock
      as compared to other hominoids. To investigate this hypothesis, we performed a
      large-scale analysis of lineage-specific rates of single-nucleotide substitutions
      among hominoids. We found that humans indeed exhibit a significant slowdown of
      molecular evolution compared to chimpanzees and other hominoids. However, the
      amount of fixed differences between humans and chimpanzees appears extremely
      small, suggesting a very recent evolution of human-specific life history traits.
      Notably, chimpanzees also exhibit a slower rate of molecular evolution compared
      to gorillas and orangutans in the regions analyzed.

PMID- 16432232
TI  - Cortical signatures of noun and verb production.
AB  - Categories like "noun" and "verb" represent the basic units of grammar in all
      human languages, and the retrieval of categorical information associated with
      words is an essential step in the production of grammatical speech. Studies of
      brain-damaged patients suggest that knowledge of nouns and verbs can be spared or
      impaired selectively; however, the neuroanatomical correlates of this
      dissociation are not well understood. We used event-related functional MRI to
      identify cortical regions that were active when English-speaking subjects
      produced nouns or verbs in the context of short phrases. Two regions, in the left
      prefrontal cortex and left superior parietal lobule, were selectively activated
      for verb trials compared with noun trials; one region in the left inferior
      temporal lobe was more active during noun production than verb production. We
      propose that these regions are involved in representing core conceptual
      properties of nouns and verbs.

PMID- 16432234
TI  - Simultaneous molecular imaging of redox reactions monitored by Overhauser
      enhanced MRI with 14N- and 15N-labeled nitroxyl radicals.
AB  - MRI has provided significant clinical utility in the diagnosis of diseases and
      will become a powerful tool to assess phenotypic changes in genetically
      engineered animals. Overhauser enhanced MRI (OMRI), which is a double resonance
      technique, creates images of free radical distributions in small animals by
      enhancing the water proton signal intensity by means of the Overhauser effect.
      Several studies have demonstrated noninvasive assessment of reactive oxygen
      species generation in small animals by using low frequency electron spin
      resonance (ESR) spectroscopy/imaging and nitroxyl radicals. In vivo ESR signal
      intensities of nitroxyl radicals decrease with time after injection; and the
      decreases are enhanced by reactive oxygen species, generated in oxidative disease
      models in a site-specific manner. In this study, we show images of nitroxyl
      radicals with different isotopes by changing the external magnetic field for ESR
      irradiation between (14)N and (15)N nuclei in field-cycled OMRI. OMRI
      simultaneously obtained dual images of two individual chemical processes.
      Oxidation and reduction were monitored in a rate-dependent manner at nanometer
      scale by labeling membrane-permeable and -impermeable nitroxyl radicals with
      (14)N and (15)N nuclei. Phantom objects containing ascorbic acid-encapsulated
      liposomes with membrane-permeable radicals but not membrane-impermeable ones show
      a time-dependent decrease of the OMRI image intensity. The pharmacokinetics in
      mice was assessed with OMRI after radical administration. This OMRI technique
      with dual probes should offer significant applicability to nanometer scale
      molecular imaging and simultaneous assessment of independent processes in gene
      modified animals. Thus, it may become a powerful tool to clarify mechanisms of
      disease and to monitor pharmaceutical therapy.

PMID- 16432236
TI  - Secondary sex ratios and male lifespan: damaged or culled cohorts.
AB  - Population stressors reportedly reduce the human secondary sex ratio (i.e., the
      odds of a newborn's being male) by, among other mechanisms, inducing the
      spontaneous abortion of males who would have been born live had mothers not been
      stressed. Controversy remains as to whether these abortions result from reduced
      maternal tolerance of males at the low end of a relatively constant distribution
      of survivability (i.e., the "culled cohort" explanation) or from shifts in the
      whole distribution of survivability such that more males fall below a relatively
      constant criterion of maternal tolerance for low survivability (i.e., the
      "damaged cohort" explanation). These alternatives make opposing predictions
      regarding the relationship between the secondary sex ratio and lifespan of male
      birth cohorts. We test the hypothesis that the secondary sex ratio among Swedish
      cohorts born in the years 1751 through 1912 predicts male cohort life expectancy
      at birth (i.e., realized lifespan). Our results support the culled cohort
      argument. We argue that these findings have implications for the basic literature
      concerned with temporal variation in the secondary sex ratio, for more applied
      work concerned with the fetal origins of adult health, and for pubic health
      surveillance.

PMID- 16432235
TI  - Pten deletion leads to the expansion of a prostatic stem/progenitor cell
      subpopulation and tumor initiation.
AB  - PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor
      suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in
      a murine model of prostate cancer recapitulates the disease progression seen in
      humans. Using defined cell lineage markers, we demonstrate that PTEN negatively
      regulates p63-positive prostatic basal cell proliferation without blocking
      differentiation. Concomitant with basal cell proliferation is the expansion of a
      prostate stem/progenitor-like subpopulation as evidenced by the progressive
      increase of stem cell antigen-1 (Sca-1)- and BCL-2-positive cells. This
      observation provides strong evidence that basal cell proliferation can be an
      initiating event for precancerous lesions. Sca-1(+) and BCL-2(+) progenitors may
      serve as cancer-initiating cells in this model.

PMID- 16432237
TI  - Nuclear localization of the Saccharomyces cerevisiae ribonucleotide reductase
      small subunit requires a karyopherin and a WD40 repeat protein.
AB  - Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the
      corresponding deoxyribonucleotides and is an essential enzyme for DNA replication
      and repair. Cells have evolved intricate mechanisms to regulate RNR activity to
      ensure high fidelity of DNA replication during normal cell-cycle progression and
      of DNA repair upon genotoxic stress. The RNR holoenzyme is composed of a large
      subunit R1 (alpha, oligomeric state unknown) and a small subunit R2 (beta(2)). R1
      binds substrates and allosteric effectors; R2 contains a diferric-tyrosyl radical
      [(Fe)(2)-Y.] cofactor that is required for catalysis. In Saccharomyces
      cerevisiae, R1 is predominantly localized in the cytoplasm, whereas R2, which is
      a heterodimer (betabeta'), is predominantly in the nucleus. When cells encounter
      DNA damage or stress during replication, betabeta' is redistributed from the
      nucleus to the cytoplasm in a checkpoint-dependent manner, resulting in the
      colocalization of R1 and R2. We have identified two proteins that have an
      important role in betabeta' nuclear localization: the importin beta homolog
      Kap122 and the WD40 repeat protein Wtm1. Deletion of either WTM1 or KAP122 leads
      to loss of betabeta' nuclear localization. Wtm1 and its paralog Wtm2 are both
      nuclear proteins that are in the same protein complex with betabeta'. Wtm1 also
      interacts with Kap122 in vivo and requires Kap122 for its nuclear localization.
      Our results suggest that Wtm1 acts either as an adaptor to facilitate nuclear
      import of betabeta' by Kap122 or as an anchor to retain betabeta' in the nucleus.

PMID- 16432238
TI  - The methyl-CpG binding protein MBD1 is required for PML-RARalpha function.
AB  - PML-RARalpha induces a block of hematopoietic differentiation and acute
      promyelocytic leukemia. This block is based on its capacity to inactivate target
      genes by recruiting histone deacetylase (HDAC) and DNA methyltransferase
      activities. Here we report that MBD1, a member of a conserved family of proteins
      able to bind methylated DNA, cooperates with PML-RARalpha in transcriptional
      repression and cellular transformation. PML-RARalpha recruits MBD1 to its target
      promoter through an HDAC3-mediated mechanism. Binding of HDAC3 and MBD1 is not
      confined to the promoter region but instead is spread over the locus. Knock-down
      of HDAC3 expression by RNA interference in acute promyelocytic leukemia cells
      alleviates PML-RAR-induced promoter silencing. We further demonstrate that
      retroviral expression of dominant-negative mutants of MBD1 in hematopoietic
      precursors compromises the ability of PML-RARalpha to block their differentiation
      and thus restored cell differentiation. Our results demonstrate that PML-RARalpha
      functions by recruiting an HDAC3-MBD1 complex that contributes to the
      establishment and maintenance of the silenced chromatin state.

PMID- 16432239
TI  - Protein structure by mechanical triangulation.
AB  - Knowledge of protein structure is essential to understand protein function. High
      resolution protein structure has so far been the domain of ensemble methods.
      Here, we develop a simple single-molecule technique to measure spatial position
      of selected residues within a folded and functional protein structure in
      solution. Construction and mechanical unfolding of cysteine-engineered
      polyproteins with controlled linkage topology allows measuring intramolecular
      distance with angstrom precision. We demonstrate the potential of this technique
      by determining the position of three residues in the structure of green
      fluorescent protein (GFP). Our results perfectly agree with the GFP crystal
      structure. Mechanical triangulation can find many applications where current bulk
      structural methods fail.

PMID- 16432240
TI  - Long-distance lateral diffusion of human Rad51 on double-stranded DNA.
AB  - Rad51 is the primary eukaryotic recombinase responsible for initiating DNA strand
      exchange during homologous recombination. Although the subject of intense study
      for over a decade, many molecular details of the reactions promoted by Rad51 and
      related recombinases remain unknown. Using total internal reflection fluorescence
      microscopy, we directly visualized the behavior of individual Rad51 complexes on
      double-stranded DNA (dsDNA) molecules suspended in an extended configuration
      above a lipid bilayer. Here we show that complexes of Rad51 can bind to and slide
      freely along the helical axis of dsDNA. Sliding is bidirectional, does not
      require ATP hydrolysis, and displays properties consistent with a 1D random walk
      driven solely by thermal diffusion. The proteins move freely on the DNA for long
      periods of time; however, sliding terminates and the proteins become immobile
      upon encountering the free end of a linear dsDNA molecule. This study provides
      previously uncharacterized insights into the behaviors of human Rad51, which may
      apply to other members of the RecA-like family of recombinases.

PMID- 16432242
TI  - Stable and robust polymer nanotubes stretched from polymersomes.
AB  - We create long polymer nanotubes by directly pulling on the membrane of
      polymersomes using either optical tweezers or a micropipette. The polymersomes
      are composed of amphiphilic diblock copolymers, and the nanotubes formed have an
      aqueous core connected to the aqueous interior of the polymersome. We stabilize
      the pulled nanotubes by subsequent chemical cross-linking. The cross-linked
      nanotubes are extremely robust and can be moved to another medium for use
      elsewhere. We demonstrate the ability to form networks of polymer nanotubes and
      polymersomes by optical manipulation. The aqueous core of the polymer nanotubes
      together with their robust character makes them interesting candidates for
      nanofluidics and other applications in biotechnology.

PMID- 16432243
TI  - Major ongoing stroke trials.

PMID- 16432241
TI  - Drosophila as a model for the identification of genes causing adult human heart
      disease.
AB  - Drosophila melanogaster genetics provides the advantage of molecularly defined P
      element insertions and deletions that span the entire genome. Although Drosophila
      has been extensively used as a model system to study heart development, it has
      not been used to dissect the genetics of adult human heart disease because of an
      inability to phenotype the adult fly heart in vivo. Here we report the
      development of a strategy to measure cardiac function in awake adult Drosophila
      that opens the field of Drosophila genetics to the study of human dilated
      cardiomyopathies. Through the application of optical coherence tomography, we
      accurately distinguish between normal and abnormal cardiac function based on
      measurements of internal cardiac chamber dimensions in vivo. Normal Drosophila
      have a fractional shortening of 87 +/- 4%, whereas cardiomyopathic flies that
      contain a mutation in troponin I or tropomyosin show severe impairment of
      systolic function. To determine whether the fly can be used as a model system to
      recapitulate human dilated cardiomyopathy, we generated transgenic Drosophila
      with inducible cardiac expression of a mutant of human delta-sarcoglycan
      (deltasg(S151A)), which has previously been associated with familial dilated
      cardiomyopathy. Compared to transgenic flies overexpressing wild-type deltasg, or
      the standard laboratory strain w(1118), Drosophila expressing deltasg(S151A)
      developed marked impairment of systolic function and significantly enlarged
      cardiac chambers. These data illustrate the utility of Drosophila as a model
      system to study dilated cardiomyopathy and the applicability of the vast genetic
      resources available in Drosophila to systematically study the genetic mechanisms
      responsible for human cardiac disease.

PMID- 16432244
TI  - Relation of parity with common carotid intima-media thickness among women of the
      study of health in Pomerania.

PMID- 16432246
TI  - Guidelines for prevention of stroke in patients with ischemic stroke or transient
      ischemic attack: a statement for healthcare professionals from the American Heart
      Association/American Stroke Association Council on Stroke: co-sponsored by the
      Council on Cardiovascular Radiology and Intervention: the American Academy of
      Neurology affirms the value of this guideline.
AB  - The aim of this new statement is to provide comprehensive and timely evidence
      based recommendations on the prevention of ischemic stroke among survivors of
      ischemic stroke or transient ischemic attack. Evidence-based recommendations are
      included for the control of risk factors, interventional approaches for
      atherosclerotic disease, antithrombotic treatments for cardioembolism, and the
      use of antiplatelet agents for noncardioembolic stroke. Further recommendations
      are provided for the prevention of recurrent stroke in a variety of other
      specific circumstances, including arterial dissections; patent foramen ovale;
      hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral
      venous sinus thrombosis; stroke among women, particularly with regard to
      pregnancy and the use of postmenopausal hormones; the use of anticoagulation
      after cerebral hemorrhage; and special approaches for the implementation of
      guidelines and their use in high-risk populations.

PMID- 16432252
TI  - Thymic stromal lymphopoietin: master switch for allergic inflammation.
AB  - Thymic stromal lymphopoietin (TSLP) is an interleukin (IL) 7-like cytokine that
      triggers dendritic cell-mediated T helper (Th)2 inflammatory responses. TSLP is
      highly expressed by keratinocytes in skin lesions of patients with atopic
      dermatitis and is associated with dendritic cell activation in situ, suggesting
      that TSLP might be a master switch for allergic inflammation at the epithelial
      cell-dendritic cell interface. New reports now establish a direct link between
      TSLP expression and the pathogenesis of atopic dermatitis and asthma in vivo, and
      begin to reveal the molecular mechanisms underlying TSLP-induced allergic
      inflammation.

PMID- 16432251
TI  - The immune paradox of sarcoidosis and regulatory T cells.
AB  - Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine
      secretion) associated with anergy (poor response to antigens in vitro and in
      vivo). We postulated that this paradoxical situation would correspond to a
      disequilibrium between effector and regulatory T lymphocytes (T reg cells). We
      show that CD4+CD25(bright)FoxP3+ cells accumulate at the periphery of sarcoid
      granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients
      with active disease. These cells exhibited powerful antiproliferative activity,
      yet did not completely inhibit TNF-alpha production. Sarcoidosis is therefore
      associated with a global T reg cell subset amplification whose activity would be
      insufficient to control local inflammation. At the same time, peripheral T reg
      cells exert powerful antiproliferative activity that may account for the state of
      anergy. Altogether, these findings advance our conceptual understanding of immune
      regulation in a way that resolves the immune paradox of sarcoidosis and permit us
      to envisage a profound clinical impact of T reg cell manipulation on immunity.

PMID- 16432253
TI  - The Bcl10-Malt1 complex segregates Fc epsilon RI-mediated nuclear factor kappa B
      activation and cytokine production from mast cell degranulation.
AB  - Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory
      diseases. Central for mast cell activation are signals from the IgE receptor
      FcepsilonRI, which induce cell degranulation with the release of preformed
      mediators and de novo synthesis of proinflammatory leukotrienes and cytokines.
      How these individual mast cell responses are differentially controlled is still
      unresolved. We identify B cell lymphoma 10 (Bcl10) and mucosa-associated lymphoid
      tissue 1 (Malt1) as novel key regulators of mast cell signaling. Mice deficient
      for either protein display severely impaired IgE-dependent late phase
      anaphylactic reactions. Mast cells from these animals neither activate nuclear
      factor kappaB (NF-kappaB) nor produce tumor necrosis factor alpha or interleukin
      6 upon FcepsilonRI ligation even though proximal signaling, degranulation, and
      leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive
      mediators of FcepsilonRI-dependent mast cell activation that selectively uncouple
      NF-kappaB-induced proinflammatory cytokine production from degranulation and
      leukotriene synthesis.

PMID- 16432254
TI  - Stable isotope tagging of epitopes: a highly selective strategy for the
      identification of major histocompatibility complex class I-associated peptides
      induced upon viral infection.
AB  - Identification of peptides presented in major histocompatibility complex (MHC)
      class I molecules after viral infection is of strategic importance for vaccine
      development. Until recently, mass spectrometric identification of virus-induced
      peptides was based on comparative analysis of peptide pools isolated from
      uninfected and virus-infected cells. Here we report on a powerful strategy aiming
      at the rapid, unambiguous identification of naturally processed MHC class I
      associated peptides, which are induced by viral infection. The methodology,
      stable isotope tagging of epitopes (SITE), is based on metabolic labeling of
      endogenously synthesized proteins during infection. This is accomplished by
      culturing virus-infected cells with stable isotope-labeled amino acids that are
      expected to be anchor residues (i.e. residues of the peptide that have amino acid
      side chains that bind into pockets lining the peptide-binding groove of the MHC
      class I molecule) for the human leukocyte antigen allele of interest.
      Subsequently these cells are mixed with an equal number of non-infected cells,
      which are cultured in normal medium. Finally peptides are acid-eluted from
      immunoprecipitated MHC molecules and subjected to two-dimensional nanoscale LC-MS
      analysis. Virus-induced peptides are identified through computer-assisted
      detection of characteristic, binomially distributed ratios of labeled and
      unlabeled molecules. Using this approach we identified novel measles virus and
      respiratory syncytial virus epitopes as well as infection-induced self-peptides
      in several cell types, showing that SITE is a unique and versatile method for
      unequivocal identification of disease-related MHC class I epitopes.

PMID- 16432255
TI  - A tandem affinity tag for two-step purification under fully denaturing
      conditions: application in ubiquitin profiling and protein complex identification
      combined with in vivocross-linking.
AB  - Tandem affinity strategies reach exceptional protein purification grades and have
      considerably improved the outcome of mass spectrometry-based proteomic
      experiments. However, current tandem affinity tags are incompatible with two-step
      purification under fully denaturing conditions. Such stringent purification
      conditions are desirable for mass spectrometric analyses of protein modifications
      as they result in maximal preservation of posttranslational modifications. Here
      we describe the histidine-biotin (HB) tag, a new tandem affinity tag for two-step
      purification under denaturing conditions. The HB tag consists of a hexahistidine
      tag and a bacterially derived in vivo biotinylation signal peptide that induces
      efficient biotin attachment to the HB tag in yeast and mammalian cells. HB-tagged
      proteins can be sequentially purified under fully denaturing conditions, such as
      8 m urea, by Ni(2+) chelate chromatography and binding to streptavidin resins.
      The stringent separation conditions compatible with the HB tag prevent loss of
      protein modifications, and the high purification grade achieved by the tandem
      affinity strategy facilitates mass spectrometric analysis of posttranslational
      modifications. Ubiquitination is a particularly sensitive protein modification
      that is rapidly lost during purification under native conditions due to ubiquitin
      hydrolase activity. The HB tag is ideal to study ubiquitination because the
      denaturing conditions inhibit hydrolase activity, and the tandem affinity
      strategy greatly reduces nonspecific background. We tested the HB tag in proteome
      wide ubiquitin profiling experiments in yeast and identified a number of known
      ubiquitinated proteins as well as so far unidentified candidate ubiquitination
      targets. In addition, the stringent purification conditions compatible with the
      HB tag allow effective mass spectrometric identification of in vivo cross-linked
      protein complexes, thereby expanding proteomic analyses to the description of
      weakly or transiently associated protein complexes.

PMID- 16432256
TI  - Detection of rare mutant K-ras DNA in a single-tube reaction using peptide
      nucleic acid as both PCR clamp and sensor probe.
AB  - The major problem of using somatic mutations as markers of malignancy is that the
      clinical samples are frequently containing a trace amounts of mutant allele in a
      large excess of wild-type DNA. Most methods developed thus far for the purpose of
      tickling this difficult problem require multiple procedural steps that are
      laborious. We report herein the development of a rapid and simple protocol for
      detecting a trace amounts of mutant K-ras in a single tube, one-step format. In a
      capillary PCR, a 17mer peptide nucleic acid (PNA) complementary to the wild-type
      sequence and spanning codons 12 and 13 of the K-ras oncogene was used to clamp
      PCR for wild-type, but not mutant alleles. The designated PNA was labeled with a
      fluorescent dye for use as a sensor probe, which differentiated all 12 possible
      mutations from the wild-type by a melting temperature (T(m)) shift in a range of
      9 to 16 degrees C. An extension temperature of 60 degrees C and an opposite
      primer 97 nt away from the PNA were required to obtain full suppression of wild
      type PCR. After optimization, the reaction detected mutant templates in a ratio
      of 1:10,000 wild-type alleles. Using this newly devised protocol, we have been
      able to detect 19 mutants in a group of 24 serum samples obtained from patients
      with pancreatic cancer. Taken together, our data suggest that this newly devised
      protocol can serve as an useful tool for cancer screening as well as in the
      detection of rare mutation in many diseases.

PMID- 16432257
TI  - Thorough validation of siRNA-induced cell death phenotypes defines new anti
      apoptotic protein.
AB  - Loss-of-function by means of RNA interference in cultured human cells enables
      rapid pathway dissection on a genome-scale. Improved siRNA design and key
      validation protocols are required to eliminate falsely identified phenotypes
      resulting from potential off-target consequences. Here, we demonstrate a
      validation strategy involving several steps for verifying cell death phenotypes
      revealed during loss-of-function screening. First, from a set of 45 novel human
      genes we identified gene candidates that, when silenced, induce apoptosis in
      cultured HeLa cells. For those candidates, we performed more extensive validation
      with multiple effective siRNAs. In addition, we designed rescue experiments
      involving candidate genes delivered exogenously and containing silent mutations
      in the siRNA target regions. Rescue of the observed knockdown phenotype
      demonstrated an original and more stringent validation of the siRNA's selectivity
      and the phenotype specificity for the target gene. As a result, our data reveals
      an anti-apoptotic function for novel human breast adenocarcinoma marker BC-2,
      adding new depth to BC-2's description as a putative tumor marker involved in
      cancer related pathways.

PMID- 16432259
TI  - Comparison of algorithms for the analysis of Affymetrix microarray data as
      evaluated by co-expression of genes in known operons.
AB  - Oligonucleotide microarrays are an informative tool to elucidate gene regulatory
      networks. In order for gene expression levels to be comparable across
      microarrays, normalization procedures have to be invoked. A large number of
      methods have been described to correct for systematic biases in microarray
      experiments. The performance of these methods has been tested only to a limited
      extend. Here, we evaluate two different types of microarray analyses: (i) the
      same gene in replicate samples and (ii) different, but co-expressed genes in the
      same sample. The reliability of the latter analysis needs to be determined for
      the analysis of regulatory networks and our report is the first attempt to
      evaluate for the accuracy of different microarray normalization methods in this
      respect. Consistent with previous results we observed a large effect of the
      normalization method on the outcome of the expression analyses. Our analyses
      indicate that different normalization methods should be performed depending on
      whether a study is aiming to detect differential gene expression between
      independent samples or whether co-expressed genes should be identified. We make
      recommendations about the most appropriate method to use.

PMID- 16432258
TI  - Sequence- and structural-selective nucleic acid binding revealed by the melting
      of mixtures.
AB  - A simple method for the detection of sequence- and structural-selective ligand
      binding to nucleic acids is described. The method is based on the commonly used
      thermal denaturation method in which ligand binding is registered as an elevation
      in the nucleic acid melting temperature (T(m)). The method can be extended to
      yield a new, higher -throughput, assay by the simple expediency of melting
      designed mixtures of polynucleotides (or oligonucleotides) with different
      sequences or structures of interest. Upon addition of ligand to such mixtures at
      low molar ratios, the T(m) is shifted only for the nucleic acid containing the
      preferred sequence or structure. Proof of principle of the assay is provided
      using first a mixture of polynucleotides with different sequences and, second,
      with a mixture containing DNA, RNA and two types of DNA:RNA hybrid structures.
      Netropsin, ethidium, daunorubicin and actinomycin, ligands with known sequence
      preferences, were used to illustrate the method. The applicability of the
      approach to oligonucleotide systems is illustrated by the use of simple ternary
      and binary mixtures of defined sequence deoxyoligonucleotides challenged by the
      bisanthracycline WP631. The simple mixtures described here provide proof of
      principle of the assay and pave the way for the development of more sophisticated
      mixtures for rapidly screening the selectivity of new nucleic acid binding
      compounds.

PMID- 16432260
TI  - High throughput detection of M6P/IGF2R intronic hypermethylation and LOH in
      ovarian cancer.
AB  - Cell surface mannose 6-phosphate/insulin-like growth factor II receptors
      (M6P/IGF2R) bind and target exogenous insulin-like growth factor II (IGF2) to the
      prelysosomes where it is degraded. Loss of heterozygosity (LOH) for M6P/IGF2R is
      found in cancers, with mutational inactivation of the remaining allele. We
      exploited the normal allele-specific differential methylation of the M6P/IGF2R
      intron 2 CpG island to rapidly evaluate potential LOH in ovarian cancers, since
      every normal individual is informative. To this end, we developed a method for
      bisulfite modification of genomic DNA in 96-well format that allows for rapid
      methylation profiling. We identified ovarian cancers with M6P/IGF2R LOH, but
      unexpectedly also found frequent abnormal acquisition of methylation on the
      paternally inherited allele at intron 2. These results demonstrate the utility of
      our high-throughput method of bisulfite modification for analysis of large sample
      numbers. They further show that the methylation status of the intron 2 CpG island
      may be a useful indicator of LOH and biomarker of disease.

PMID- 16432262
TI  - Unbiased in vitro selection reveals the unique character of the self-cleaving
      antigenomic HDV RNA sequence.
AB  - In order to revisit the architecture of the catalytic center of the antigenomic
      hepatitis delta virus (HDV) ribozyme we developed an unbiased in vitro selection
      procedure that efficiently selected novel variants from a relatively small set of
      sequences. Using this procedure we examined all possible variants from a pool of
      HDV ribozymes that had been randomized at 25 positions (4(25)). The isolated set
      of sequences shows more variability than do the natural variants. Nucleotide
      variations were found at all randomized positions, even at positions when the
      general belief was that the specific base was absolutely required for catalytic
      activity. Covariation analysis supports the presence of several base pairs,
      although it failed to propose any new tertiary contacts. HDV ribozyme appears to
      possess a greater number of constraints, in terms of sequences capable of
      supporting the catalysed cleavage, than do other catalytic RNAs. This supports
      the idea that the appearance of this catalytic RNA structure has a low
      probability (i.e. is a rare event), which may explain why to date it has been
      found in nature only in the HDV. These contrasts with the hammerhead self
      cleaving motif that is proposed to have multiple origins, and that is widespread
      among different organisms. Thus, just because a self-cleaving RNA motif is small
      does not imply that it occurs easily.

PMID- 16432264
TI  - Practical perspectives on the use of tipranavir in combination with other
      medications: lessons learned from pharmacokinetic studies.
AB  - Drug-drug interactions are a major practical concern for physicians treating
      human immunodeficiency virus (HIV) because of the many medications that HIV
      positive patients must take. Pharmacokinetic drug interactions can occur at
      different levels (absorption, distribution, metabolism, excretion) and are
      difficult to predict. Of all the processes that give rise to drug interactions,
      metabolism by cytochrome P450 (CYP3A) is the most frequent. Moreover, medications
      prescribed to HIV-positive patients may also be CYP3A inhibitors and inducers:
      Tipranavir, in the absence of ritonavir, is a CYP3A inducer, and ritonavir is a
      CYP3A inhibitor. Fortunately, the drug interactions between tipranavir
      coadministered with ritonavir and other antiretroviral medications or with other
      medications commonly used in HIV therapy are well characterized. This review
      summarizes the pharmacokinetic interactions between tipranavir/ritonavir and 11
      other antiretroviral medications and between tipranavir/ritonavir and drugs used
      to treat opportunistic infections such as fungal infections, antiretroviral
      treatment-related conditions such as hyperlipidemia, and side effects such as
      diarrhea.

PMID- 16432261
TI  - Engineered external guide sequences are highly effective in inducing RNase P for
      inhibition of gene expression and replication of human cytomegalovirus.
AB  - External guide sequences (EGSs), which are RNA molecules derived from natural
      tRNAs, bind to a target mRNA and render the mRNA susceptible to hydrolysis by
      RNase P, a tRNA processing enzyme. Using an in vitro selection procedure, we have
      previously generated EGS variants that efficiently direct human RNase P to cleave
      a target mRNA in vitro. In this study, a variant was used to target the
      overlapping region of the mRNAs encoding human cytomegalovirus (HCMV) essential
      transcription regulatory factors IE1 and IE2. The EGS variant was approximately
      25-fold more active in inducing human RNase P to cleave the mRNA in vitro than
      the EGS derived from a natural tRNA. Moreover, a reduction of 93% in IE1/IE2 gene
      expression and a reduction of 3000-fold in viral growth were observed in HCMV
      infected cells that expressed the variant, while cells expressing the tRNA
      derived EGS exhibited a reduction of 80% in IE1/IE2 expression and an inhibition
      of 150-fold in viral growth. Our results provide the first direct evidence that
      EGS variant is highly effective in blocking HCMV gene expression and growth and
      furthermore, demonstrate the feasibility of developing effective EGS RNA variants
      for anti-HCMV applications by using in vitro selection procedures.

PMID- 16432263
TI  - Induction of the lac promoter in the absence of DNA loops and the stoichiometry
      of induction.
AB  - In vivo induction of the Escherichia coli lactose operon as a function of inducer
      concentration generates a sigmoidal curve, indicating a non-linear response.
      Suggested explanations for this dependence include a 2:1 inducer-repressor
      stoichiometry of induction, which is the currently accepted view. It is, however,
      known for decades that, in vitro, operator binding as a function of inducer
      concentration is not sigmoidal. This discrepancy between in vivo and in vitro
      data has so far not been resolved. We demonstrate that the in vivo non-linearity
      of induction is due to cooperative repression of the wild-type lac operon through
      DNA loop formation. In the absence of DNA loops, in vivo induction curves are
      hyperbolic. In the light of this result, we re-address the question of functional
      molecular inducer-repressor stoichiometry in induction of the lac operon.

PMID- 16432265
TI  - Disposition kinetics and tolerance of escalating single doses of ramelteon, a
      high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of
      insomnia.
AB  - Ramelteon is a selective MT(1)/MT(2) receptor agonist, indicated for insomnia
      treatment. Safety, tolerance, pharmacokinetics, and cognitive performance were
      evaluated following increasing ramelteon doses. Healthy adults (35-65 years) were
      randomly assigned to receive 1 of 5 oral ramelteon doses (4, 8, 16, 32, or 64 mg;
      n = 8 per group) or placebo (n = 20). C(max) and AUC(infinity) (mean [%CV])
      increased with each dose: C(max) = 1.15 (109), 5.73 (97), 6.92 (77), 17.4 (76),
      and 25.9 (77) ng/mL, respectively, and AUC(infinity) = 1.71 (114), 6.95 (108),
      9.88 (78), 22.5 (80), and 36.1 (71 n x h/mL), respectively. Mean T(max) values of
      0.75 to 0.94 hours and mean elimination half-life of 0.83 to 1.90 hours remained
      relatively constant. Ramelteon was extensively metabolized. Besides ramelteon, 4
      metabolites, M-I, M-II, M-III, and M-IV, were measured in serum. Metabolite M-II,
      which has shown weak ramelteon-like activity in vitro, was the major metabolite
      in serum. Digit Symbol Substitution Test and visual analog scale alertness scores
      were similar across all dose groups and did not differ from placebo. All adverse
      events were mild or moderate and resolved before study completion.

PMID- 16432266
TI  - Fingolimod (FTY720) in severe hepatic impairment: pharmacokinetics and
      relationship to markers of liver function.
AB  - The authors assessed the impact of severe hepatic impairment on the disposition
      of fingolimod--a sphingosine-1-phosphate receptor immunomodulator primarily
      metabolized by CYP4F2--in 6 patients and 6 matched healthy controls who received
      a single 5-mg oral dose. Compared with healthy controls, severe hepatic-impaired
      subjects had a doubled area under the concentration time curve (AUC) and 50%
      prolonged elimination half-life but a similar peak blood concentration. When
      these data were combined with those from a previous study in mild and moderate
      hepatic-impaired subjects, there were significant positive correlations between
      fingolimod AUC versus bilirubin (r = 0.683) and prothrombin time (r = 0.777) and
      a significant negative correlation versus albumin (r = 0.578), confirming the
      importance of liver function for fingolimod clearance. For patients with severe
      hepatic impairment (Child-Pugh class C), a standard first dose of fingolimod
      could be given followed by a maintenance dose that is reduced by half from the
      normal maintenance dose.

PMID- 16432267
TI  - Variability in renal clearance of substrates for renal transporters in chinese
      subjects.
AB  - The authors evaluated the inter- and intraindividual variability in the renal
      clearance of substrates of organic anion transporters (OAT) or organic cation
      transporters (OCT) using repeated drug application procedures. Two OAT substrates
      (ampicillin and cephalexin) and 2 OCT substrates (famotidine and metformin) were
      selected. Each drug was administered orally twice to healthy subjects, with
      sample sizes ranging from 12 to 28 (using bioequivalent formulations of each
      drug). The inter-(delta(inter)) and intrasubject (delta(intra)) variances in
      renal clearance were estimated based on analysis of variance, and the genetic
      contribution (r(GC)) was calculated as (delta(inter - intra))/delta(inter). The
      renal clearances of ampicillin, cephalexin, famotidine, and metformin averaged
      5.21 (range, 2.87-11.20), 3.01 (range, 1.50-3.82), 4.96 (range, 2.84-8.17), and
      9.44 (range, 5.66-15.43) mL/min/kg, with mean intraindividual coefficients of
      variation of 17.7%, 7.3%, 13.5%, and 9.0% and r(GC) values of 0.75, 0.89, 0.81,
      and 0.93, respectively. These high r(GC) values suggest a potential significant
      genetic contribution by the renal OATs and OCTs in Chinese subjects. Further
      studies in a larger population are needed to confirm the importance of these
      results as well as to identify specific genetic variants in these transporters
      responsible for such variability.

PMID- 16432269
TI  - Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally
      disintegrating tablet administered with or without water in healthy subjects: an
      open-label, randomized, single-dose, 3-period crossover study.
AB  - This open-label, 3-period crossover study compared the plasma concentration
      profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc),
      and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At
      each period, subjects received a single dose of either 10-mg rizatriptan tablet,
      10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that
      ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater
      geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the
      time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of
      each dosing method. ODTc had a statistically significantly greater geometric mean
      AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P < .001). ODTc
      had a slightly, but not statistically significantly, greater geometric mean AUC(0
      1h) compared with rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The
      median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc
      showed a slightly, but not significantly, faster rate of absorption compared with
      tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies
      are needed to determine whether this pharmacokinetic difference produces
      differential efficacy in a clinical setting.

PMID- 16432268
TI  - Pharmacokinetics of olanzapine after single-dose oral administration of standard
      tablet versus normal and sublingual administration of an orally disintegrating
      tablet in normal volunteers.
AB  - Olanzapine (OLZ) is a second-generation antipsychotic agent available in 2 solid
      oral dosage forms, a standard oral tablet (SOT) and an orally disintegrating
      tablet (ODT). This study assessed the absorption of each by different routes of
      administration. Secondarily, the influence of P-glycoprotein (P-gp) genotype was
      assessed. It was hypothesized that more rapid absorption of the OLZ ODT would
      occur when administered sublingually versus standard oral administration. A
      randomized, 3-way crossover study assessed the 5-mg OLZ formulations in healthy
      volunteers (n = 10). Blood was collected (0-8 hours) to assess OLZ
      pharmacokinetics using liquid chromatography/mass spectrometry. Both routes of
      ODT administration resulted in more measurable early concentrations relative to
      SOT. However, there were no statistically significant differences observed
      between any of the OLZ exposures for observed pharmacokinetic parameters (C(max),
      T(max), AUC(0-8h)). The homozygous TT genotype for P-gp resulted in an increased
      AUC of OLZ for SOT administration but not for either condition where sublingual
      absorption could occur.

PMID- 16432271
TI  - The effect of ravuconazole on the pharmacokinetics of nelfinavir in healthy male
      volunteers.
AB  - An open-label, nonrandomized study was conducted to assess the effect of
      ravuconazole on the pharmacokinetics of concomitantly administered nelfinavir.
      Healthy volunteers received 750 mg nelfinavir on day 1, 750 mg nelfinavir and 400
      mg ravuconazole on day 2, 400 mg ravuconazole on days 3 to 28, and 750 mg
      nelfinavir and 400 mg ravuconazole on day 29. The geometric means of C(max) and
      area under the curve of nelfinavir coadministered with ravuconazole were 30.7%
      and 31.9% higher on day 2 and 7.9% and 16.2% lower on day 29, respectively,
      compared to the corresponding values on day 1. These findings are consistent with
      the potential for ravuconazole to both inhibit and induce CYP3A isozymes. The
      alterations in the systemic exposure to nelfinavir were within the range defined
      by the 90% confidence interval. The study data indicate that coadministration of
      ravuconazole did not result in a clinically significant change in the plasma
      levels of nelfinavir.

PMID- 16432270
TI  - Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine
      tablets in dose-escalation trials.
AB  - In this investigation, the pharmacokinetic and pharmacodynamic properties were
      determined of multiple doses of sublingual tablets containing either
      buprenorphine alone or buprenorphine and naloxone. Subjects were experienced
      opiate users who received escalating doses (4-24 mg) of buprenorphine either
      alone or in combination with naloxone. Peak concentration (Cmax) and area under
      the concentration-time curves (AUCs) increased for both buprenorphine and
      naloxone with escalating doses. Significant differences were found across the
      range of doses administered for dose-adjusted Cmax for both tablet formulations
      and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both
      formulations, the maximal buprenorphine-induced decreases in respiratory rate and
      pupil diameter did not vary significantly across doses. Several of the subjective
      effects of buprenorphine did not increase as the dose of buprenorphine
      administered was increased. These findings are consistent with the ceiling effect
      associated with the partial agonist actions of buprenorphine. They also indicate
      a lack of dose proportionality for buprenorphine sublingual tablets, at least
      during the times at which levels of this agent are highest.

PMID- 16432273
TI  - Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9
      substrate.
AB  - The effect of Ginkgo biloba on the activity of CYP2C9, the isoform responsible
      for S-warfarin clearance, was assessed in 11 healthy volunteers who received
      single 100-mg doses of flurbiprofen, a probe substrate for CYP2C9. Subjects also
      received either a standardized G biloba leaf preparation (Ginkgold, 3 doses of
      120 mg) or matching placebo in a randomized, double-blind, 2-way crossover study.
      Mean kinetic variables for flurbiprofen with either placebo or G biloba were
      elimination half-life, 3.9 versus 3.5 hours; total AUC, 57 versus 55 microg/mL h;
      and oral clearance, 32.9 versus 31.6 mL/min. None of these differences was
      significant. Based on highperformance liquid chromatography analysis, each 60-mg
      Ginkgold tablet contained 6.6 mug of amentoflavone and 61.2 microg of quercetin,
      both previously identified as CYP2C9 inhibitors. These amounts were apparently
      too low to inhibit CYP2C9 function in vivo. The results confirm previous
      controlled clinical studies showing no effect of ginkgo on the kinetics or
      dynamics of warfarin.

PMID- 16432274
TI  - Effect of R667, a novel emphysema agent, on the pharmacokinetics of midazolam in
      healthy men.
AB  - The purpose of this study was to investigate the potential for a CYP3A4-mediated
      drug interaction between R667 and midazolam (MDZ) in healthy subjects. R667 is
      metabolized by CYP3A4 and therefore may interact with CYP3A4 substrates. In the
      present study, 18 healthy male subjects received a single 15-mg oral dose of MDZ
      with and without R667 coadministration. Serial blood samples were collected
      predose and up to 24 hours after each MDZ dose for pharmacokinetic (PK)
      evaluation. The PK parameters for MDZ, R667, and metabolites were estimated using
      noncompartmental methods. MDZ exposure was very similar in the presence and
      absence of R667 (C(max) = 50.8 vs 46.2 ng/mL; AUC(0-last) = 215 vs 216 ng.h/mL;
      AUC(0-last) ratio = 0.26 vs 0.26, respectively). R667 exposure was not affected
      by midazolam coadministration as compared with historical data. Based on the
      results of this study, no significant pharmacokinetic interaction should be
      anticipated between R667 and CYP3A4 substrates.

PMID- 16432272
TI  - Assessing the clinical significance of botanical supplementation on human
      cytochrome P450 3A activity: comparison of a milk thistle and black cohosh
      product to rifampin and clarithromycin.
AB  - Phytochemical-mediated modulation of cytochrome P450 enzymes (CYPs) may underlie
      many herb-drug interactions. This study's purpose was to assess the effects of
      milk thistle and black cohosh supplementation on CYP3A activity and compare them
      to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin.
      Healthy volunteers were randomly assigned to receive a standardized milk thistle
      (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received
      rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls
      for CYP3A induction and inhibition, respectively. Midazolam was administered
      orally before and after each supplementation and control period. The effects of
      milk thistle, black cohosh, rifampin, and clarithromycin on midazolam
      pharmacokinetics were determined using noncompartmental techniques. Unlike those
      observed for rifampin and clarithromycin, midazolam pharmacokinetics was
      unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear
      to have no clinically relevant effect on CYP3A activity in vivo.

PMID- 16432275
TI  - Limited sampling models for oral midazolam: midazolam plasma concentrations, not
      the ratio of 1-hydroxymidazolam to midazolam plasma concentrations, accurately
      predicts AUC as a biomarker of CYP3A activity.
AB  - Oral midazolam is used as a phenotyping probe for cytochrome P450 (CYP) 3A
      activity and requires multiple plasma samples to measure drug exposure. Limited
      sampling is a useful strategy for optimizing sampling and reducing costs and
      labor. We studied limited sampling models using multiple linear regressions to
      predict the area under the concentration versus time curve (AUC) of midazolam
      using either midazolam plasma concentrations or the ratio of 1-hydroxymidazolam
      (1-OH MDZ) to midazolam plasma concentrations. CYP3A baseline activity data for
      oral midazolam from previous studies were used (45 healthy adults for models
      using midazolam plasma concentrations and 41 healthy adults for models using the
      ratios of 1-OH MDZ to midazolam plasma concentrations). Limited sampling models
      were derived, validated, and evaluated for precision and bias. Two equations
      using the time points at 0.5 and 6 hours and 0.5, 2, and 6 hours were acceptable
      and predictive of midazolam AUC using midazolam plasma concentrations. No 1-OH
      MDZ to midazolam plasma concentration ratios accurately predicted midazolam AUC.

PMID- 16432276
TI  - Investigation of the potential relationships between plasma voriconazole
      concentrations and visual adverse events or liver function test abnormalities.
AB  - This study investigated the relationship between plasma voriconazole
      concentrations (pVC) and risk of visual adverse events (VAEs) or liver function
      test (LFT) abnormalities using longitudinal logistic regression. Seven-day mean
      pVC were calculated from 2,925 plasma samples (1,053 patients); in each 7-day
      period, the presence or absence of VAEs/abnormal LFTs was analyzed as a binary
      outcome variable. There was a relationship between pVC and risk of VAE (P = .011)
      and a weaker, but statistically significant, association with risk of aspartate
      transaminase (AST), alkaline phosphatase (ALP), or bilirubin but not alanine
      transaminase (ALT) abnormalities. The odds ratios of LFT abnormalities per 1
      mug/mL pVC increase ranged from 1.07 to 1.17. Maximum weekly occurrences were
      10%, 8%, 5%, and 14% for AST, ALT, ALP, and bilirubin abnormalities,
      respectively. Receiver-operating characteristic curve analysis indicates that
      individual pVC cannot be used to predict subsequent LFT abnormalities.

PMID- 16432277
TI  - High density lipoproteins bind Abeta and apolipoprotein C-II amyloid fibrils.
AB  - Disease-associated amyloid deposits contain both fibrillar and nonfibrillar
      components. The majority of these amyloid components originate or coexist in the
      bloodstream. To understand the nature of the interaction between the nonfibrillar
      and fibrillar components, we have developed a centrifugation method to isolate
      fibril binding proteins from human serum. Amyloid fibrils composed of either
      Abeta peptide or apolipoprotein C-II (apoC-II) cosedimented with specific serum
      proteins. Gel electrophoresis, mass spectrometry peptide fingerprinting, and
      Western analysis identified the major binding species as proteins found in HDL
      particles, including apoA-I, apoA-II, apoE, clusterin, and serum amyloid A.
      Sedimentation analysis showed that purified human HDL and recombinant apoA-I
      lipid particles bound directly to Abeta and apoC-II amyloid fibrils. These
      studies reveal a novel function of HDL that may contribute to the well
      established protective effect of this lipoprotein class in heart disease.

PMID- 16432278
TI  - Inhibition of the expression of lysyl oxidase and its substrates in cadmium
      resistant rat fetal lung fibroblasts.
AB  - Copper (Cu)-dependent lysyl oxidase (LO) catalyzes crosslinking of collagen and
      elastin stabilizing the extracellular matrix (ECM). Chronic inhalation of cadmium
      (Cd), a toxic metal, induces emphysema. To probe mechanisms of Cd injury to the
      lung, we developed Cd-resistant (CdR) cells from rat fetal lung fibroblasts
      (RFL6) by chronic exposure to CdCl(2) from 1 to 40 microM and further examined
      their expressions of LO, LO substrates, and Cu-scavenging thiols. Levels of
      cellular thiols, metallothionein, and glutathione in CdR cells were elevated to
      13.0- and 3.2-fold of parental controls, respectively, whereas LO mRNA and
      protein levels were markedly reduced in these cells, with catalytic activity
      declining to only 16% of the parental control. A conspicuous 52 kDa species
      rather then the normal 50 kDa proenzyme appeared in the CdR cell extract but not
      in the conditioned medium, which was codistributed with the endoplasmic reticulum
      marker [DiOC5(3)] within the cell, implying the Cd-induced 52 kDa species as a
      product of an abnormal LO-processing defect in secretion. Addition of Cu into CdR
      cell cultures enhanced the expression of LO mRNA, protein and catalytic
      activities reflecting limitation of Cu bioavailability for LO in these cells.
      With inhibition of LO, CdR cells also displayed downregulation of collagen and
      elastin, substrates of LO. Restoration of collagen synthesis by exposure of CdR
      cells to purified LO or Cu suggests that inhibition of LO and limitation of Cu
      cofactor by Cd, as key phenotype changes, accelerated collagen and elastin
      damage, a critical event pertinent to emphysema pathogenesis.

PMID- 16432279
TI  - [Regenerative medical therapy and prosthodontics].
AB  - The relation between prosthodontics and regenerative medical therapy was taken up
      as a theme at symposiums in the 112th and 113th scientific meeting of Japan
      Prosthodontic Society. In this article, these two symposiums are summarized, and
      academic conference presentations in the scientific meeting of Prosthodontic
      Society and the content of scientific papers published in the past 21 years are
      listed by theme, and how the academic society members had worked on themes such
      as basic medical research and regenerative medical therapy are verified. As a
      result, it is clarified that reports on biological research and research of
      regenerative medical therapy carried out from the prosthodontic viewpoint have
      increased in recent years. However, reports concerning biological findings on
      dental implants have not increased. It is shown that we have to think about the
      future direction again regarding the relations with recent regenerative medical
      therapy. In addition, the necessity of regenerative medical therapy in
      prosthodontic studies in the future is discussed including some personal
      opinions. The theme on which we have worked to date is not necessarily far from
      regenerative medical therapy, and research in the prosthodontic field will
      contribute to the development of regenerative medical therapy greatly if we
      appropriately adopt its concept and techniques. I hope that this article will
      have a good influence on the direction of research of academic society members,
      especially young members in the future.

PMID- 16432280
TI  - [Functional recovery with prosthetic management for segmental resection of the
      mandible without reconstruction].
AB  - PATIENT: The patient, a 54-year-old male, consulted the Oral Surgery Department
      of Iwate Medical University Hospital with a complaint of a mass in the left oral
      base in June 1992. In September 1992, the patient was diagnosed as having cancer
      in the left mandibular base, and the tumor was excised by resection of the entire
      cervical region on the left side. Since radiation osteonecrosis in the left
      mandible and mandibular fracture were detected, segmental excision of the left
      mandible was performed in March 1993. Although the postoperative course was good
      without reconstruction, the patient consulted the Second Prosthetic Department to
      achieve functional recovery in February 1996. This patient had no occlusal
      contact between the maxilla and mandible because the mandible shifted to the
      affected side. After fixation of a mandibular prosthetic appliance for the
      defective mandible, a palatal plate for the maxilla in occlusal contact with the
      mandibular dentition and mandibular prosthetic appliance were fixed in November
      1997. After fixation of a new mandibular prosthetic appliance and dentures for
      the maxilla with palatal ramp in April 2001, masticatory function was observed to
      have improved with control of the mandible. DISCUSSION: To prevent the mandibular
      shift and improvement of the masticatory function, a palatal plate with a palatal
      ramp in the occlusal contact region was fixed, and a balance of the masticatory
      muscles could be maintained. An evaluation of the level of improvement in the
      masticatory function and the pronunciation function indicated that the mandibular
      prosthetic appliance and palatal plate with a palatal ramp in the occlusal
      contact region increased the kind of food that the patient could take. Moreover,
      by enlarging the narrow Donders space, the pronunciation was improved.
      CONCLUSIONS: Fixation of a palatal plate with a palatal ramp in the occlusal
      contact region without reconstruction of the mandibular bone was useful for the
      control of mandibular deviation to the affected side and improvement of the
      masticatory function.

PMID- 16432281
TI  - [Chromatic study of all-ceramic restorations--influence of abutment tooth color
      on color tone of copings].
AB  - PURPOSE: Recently, the use of all-ceramic crowns has spread widely in clinical
      applications to meet the demand for both functional and esthetically-pleasing
      restorations. In making all-ceramic crowns, it is necessary to reproduce the
      shape and color near to those of the natural teeth. However, the color shades of
      abutments might influence the color of the copings which are made of material
      with high transparency. This study examined the influence of the color shades of
      the abutments on the final color of copings for three kinds of all-ceramic core
      materials: Empress, Empress 2 (IVOCLAR VIVADENT), and Procera AllCeram (Nobel
      Biocare). METHODS: Copings with 0.5 mm in thickness were fabricated by using
      Empress (TC1), Empress 2 (100), and Procera AllCeram (white) core materials for
      an upper-right central incisor. Abutments were made by using six kinds of die
      materials of the Empress system (ST1, ST2, ST3, ST5, ST8, ST9), gold-silver
      palladium alloy, gold alloy, and experimental black body. Copings were inserted
      in each abutment and the final color of the central part of the buccal surface
      was measured using a spectrophotometer according to the L*a*b* color system.
      RESULTS: Regardless of the color shades of the abutments, the chroma values of
      the copings rose in the order of Empress, Empress 2, and Procera, and the values
      of lightness rose in the order of Empress, Procera, and Empress 2. When the final
      color of each coping measured under the wet and dry conditions were compared, the
      difference in chroma was great. CONCLUSIONS: Within the limitations of this
      study, the results suggest that the influence of the color shades of the
      abutments on the final color of the three kinds of copings is small in the order
      of Empress, Procera, and Empress 2. In clinical and dental laboratory operations,
      it is hoped to observe and measure the color of copings and restorations under
      the wet condition.

PMID- 16432282
TI  - [Comparison of shortened dental arches with complete dental arches by clinical
      examinations].
AB  - PURPOSE: Recently, there have been reports in favor of avoiding prosthodontic
      intervention as Shortened Dental Arch (SDA) in Northern Europe. However, many of
      these reports were conducted through interviews and questionnaires, and so the
      evaluation of the results lacked objectivity. Thus, this research analyzed the
      clinical status of SDA. METHODS: For the selection of subjects, seven patients
      (average age: 59.3+/-13.2 years old) who had had the free-end missing on both
      sides of the lower dental arches for over five years were chosen as the SDA
      group. As the complete dental arch (CDA) group, seven patients (average age:
      61.3+/-9.6 years old) who had no clinical defects in their masticatory function,
      and who had no missing teeth other than the third molar, were selected.
      Measurement items in this study were occlusal contact areas for the mandible
      premolar, center of force, occlusion time, and interdentium. The Mann-Whitney U
      test was used for statistical analysis and the significance level was assumed to
      be 5%. RESULTS: The results were as follows: 1) The occlusal contact area of the
      mandible premolar of SDA was significantly large. 2) The center of force of SDA
      was significantly forward. 3) The occlusion time of SDA had a tendency of
      prolongation. 4) Interdentium of 3 2 | 2 3, 4 3 | 3 4 and 5 4 | 4 5 of SDA were
      significantly wide. CONCLUSIONS: There were differences of clinical parameters
      between SDA and CDA in this study.

PMID- 16432284
TI  - [Masticatory muscle activity during exertion of the back].
AB  - PURPOSE: The lower jaw is considered to be fixed during body exercise. However,
      its mechanism remains to be elucidated. The present study investigated
      masticatory muscle activity during of the back. METHODS: The subjects were 9
      healthy dentulous patients. The maximum back strength of the patients was
      measured with a back-dynamometer. Muscle activities of the temporal, masseter and
      digastric muscles during exertion of the back and mastication of peanuts were
      measured. Muscle activities of the temporal and masseter muscle during maximum
      voluntary clenching and that of the digastric muscles during exertion of
      resistance against forced mouth opening were also measured, and maximum voluntary
      muscle activities were obtained. The relative percentage of each masticatory
      muscle against maximum voluntary activity was calculated from the data obtained,
      and muscle activities during exertion of the back, mastication of peanuts and
      maximum muscle activity were compared. RESULTS: Muscle activities of the
      temporal, masseter and digastric muscles during exertion of back muscles against
      maximum voluntary muscle activity were 32.1%, 26.4% and 97.4% respectively.
      Muscle activities of these muscles during mastication of peanuts against maximum
      voluntary muscle activity were 40.7%, 36.0% and 17.3% respectively. CONCLUSIONS:
      Muscle activities during exertion of the back were 30% in the temporal and
      masseter muscle, and approximately 100% in the digastric muscles. The result
      suggests that the digastric muscles play a key role in fixing the mandible in all
      masticatory muscles including jaw-opening and closing muscles. People exert back
      strength not only in sports but also in daily life. This study demonstrates the
      stronger involvement of the digastric muscles in fixation of the mandible during
      exercise than during strong clenching. The results are of interest in terms of
      mandibular position, occlusal contact and the load on the temporomandibular joint
      (TMJ) since there is no wide mouth opening.

PMID- 16432283
TI  - [Stress releasing effect of tissue conditioning materials for interim dentures
      after implant installation].
AB  - PURPOSE: The main objective of this study was to examine the influence of the
      thickness and its longitudinal change within the limited denture space on the
      stress releasing effect for installed implants during the healing period of a two
      stage procedure. METHODS: As for the tissue conditioning material, Tissue
      Conditioner (Shofu, Kyoto, Japan) with the designated powder liquid ratio was
      used. The force transmitted to the implant with the material 5 min after the
      mixing was measured by a miniature pressure sensor in the position of the implant
      head (Kyowa, Tokyo, Japan). Measurements were repeated with the material
      preserved in the water for one and two weeks. Load of 2 kg was applied with a 3
      mm diameter round tip using a static loading machine for 2 min to the center of
      the flat type denture model. The model consisted of denture, mucosa, tissue
      conditioning material and implant where the first three variables were changed as
      in the oral cavity. Influence of thickness of each variable was examined
      longitudinally. RESULTS: Force measured with any thickness of tissue conditioning
      material was smaller than that without the material. The stress releasing effect
      did not change with change of the longitudinal material property up to two weeks.
      CONCLUSIONS: Within the limitations of our study, it was suggested that the
      stress releasing effect of the tissue conditioning material for the installed
      implant was not influenced by the thickness or change of longitudinal property.

PMID- 16432285
TI  - [Study on the number of denture adjustments in complete denture wearers-
      relationship to mandibular ridge shape].
AB  - PURPOSE: This study investigated the relationship between the degree of
      mandibular alveolar ridge resorption and the number of denture adjustments after
      insertion of dentures in complete denture wearers. METHODS: The subjects were 77
      complete denture patients (34 males, 43 females, mean age 69.1+/-8.1 years).
      Using bite plates of Gothic arch tracing for new denture production, the width,
      height, and inclination toward the tentative occlusal plane of the mandibular
      alveolar ridge corresponding to the canine areas (C), first premolar areas (P1),
      second premolar areas (P2), and first molar areas (M1) were measured bilaterally,
      and the relationship with the number of denture adjustment was evaluated.
      RESULTS: The mean of number of denture adjustments was 4.4+/-1.8 times (male 3.8
      times, female 5.0 times), showing a significant difference between males and
      females (p<0.01). The alveolar ridge mean width was C: 9.7 mm, P1: 10.4 mm, P2:
      11.5 mm, and M1: 13.0 mm respectively. The alveolar ridge mean height was C: 4.3
      mm, P1: 4.6 mm, P2: 4.9 mm, and M1: 5.2 mm. The alveolar ridge mean inclination
      was C: 11.2 degrees, P1: 13.5 degrees, P2: 15.4 degrees, and M1: 18.8 degrees.
      The width and height of the mandibular alveolar ridge in C, P1, P2, and M1 were
      significantly larger in males than in females (p<0.05). The height of mandibular
      alveolar ridge was significantly lower in high number of denture adjustment than
      in low number of denture adjustment (p<0.05). CONCLUSION: Complete denture
      wearers showed a high relation between the number of denture adjustment and the
      mandibular alveolar ridge height.

PMID- 16432286
TI  - [Behavioral study of denture acceptance. Part 1 qualitative investigation of
      linguistic data and validity of coding process].
AB  - PURPOSE: The purpose of this study was to extract questionnaire items based on
      qualitative data from edentulous patients obtained by individual interview.
      METHODS: Forty-three patients (20 complete denture, 20 partial denture and three
      non-denture wearers) who had visited the dental hospital affiliated to Nihon
      University School of Dentistry at Matsudo voluntarily agreed to be interviewed
      about their denture use with ten questions structured by Triandis theory in an
      open-rended manner. Responses to interview were recorded by voice recorder and
      qualitatively analyzed into linguistic and coded items, i.e. fragmentation and
      editing of recorded data followed by linguistic coding. The coded items were then
      classified into one of the 4 domains of Triandis theory: intentions of their
      denture acceptance (I), social factor (SF), affect (A) and perceived consequences
      (PC). RESULTS: The analysis of qualitative data, description, fragmentation and
      editing, accumulated 722 linguistic items. These were summarized into 72 codes,
      and classified into twelve I, nine SF, nine A and 42 PC. CONCLUSIONS: The 72
      coded items, which summarized the edentulous qualitative data including the 4
      domains of Traindis theory, are considered useful as questionnaire items of
      behavioral investigation. Further large-scale studies using this questionnaire
      will be needed to clarify the reasons for denture acceptance.

PMID- 16432287
TI  - [Effect of differences in guide plane configuration on abutment tooth
      displacement during clasp insertion].
AB  - PURPOSE: Three types of guide plane were compared to clarify the effect of guide
      plane setting conditions on abutment displacement which arises when an Akers
      clasp is inserted. METHODS: An experimental model with an artificial periodontal
      membrane made of hydrophilic vinyl polysiloxane impression material was created.
      Abutments given a guide plane with only a clasp body (G1), a guide plane whose
      span extended as far as the reciprocal clasp arm shoulder region diametrically
      opposite the retention area (G2), and a guide plane for the entire reciprocal
      clasp arm region (G3) were created, and an Akers clasp was made for each
      abutment. The amount of abutment displacement and the degree of rotation that
      arose in the abutment when the Akers clasp was inserted were detected with three
      laser displacement sensors for comparison. RESULTS: The amount of abutment
      displacement that arose when the clasp was inserted was higher with G1 than with
      G2 and G3 in the lingual and distal directions, and no difference was seen
      between G2 and G3. It was lower with G1 than with G2 and G3 in the buccal
      direction, and no difference was seen between G2 and G3. It was high with G1 in
      the mesial direction, and the abutment rotation was high, whereas they were low
      in the case of G3. A difference was seen between each condition. CONCLUSIONS:
      Differences in guide plane setting conditions affected the abutment displacement
      that arose when an Akers clasp was inserted, suggesting that a difference in
      reciprocal action is seen depending on the setting conditions of the guide plane.

PMID- 16432288
TI  - [Improvement of aesthetics by porcelain laminate veneers].
AB  - PATIENT: The patient consulted our department with a chief complaint of aesthetic
      problems due to anterior tooth discoloration. Since improvement by bleaching was
      considered impossible, porcelain laminate veneer restorations were performed.
      DISCUSSION: Insertion took too long for the patient's satisfaction due to the
      repetition of color adjustment and recontouring. The veneer preparation area
      should be limited to enamel; however when dentin is exposed, it is important to
      treat with primer before adhesion. CONCLUSION: In this case, establishing a
      selection criterion for bleaching, a combined approach was also considered.
      Although the preparation area is limited to enamel, phosphoric acid etching
      should be avoided when dentin is exposed. The treatment process should be
      arranged so as to reduce the manipulation period.

PMID- 16432289
TI  - [Sectional acrylic dentures for a partially edentulous patient with microstomia:
      a clinical report].
AB  - PATIENT: The patient was a 48-year-old partially edentulous male with
      microstomia. His chief complaints were masticatory disturbance and aesthetic
      problems caused by missing teeth. After trayless impressions for diagnostic casts
      were made, sectional trays and a sectional record block were used for the
      definitive impression and maxillomandibular registration. Maxillary and
      mandibular acrylic sectional dentures were simultaneously delivered. DISCUSSION:
      Low caries activity, minimal occlusal force, appropriate plaque control, and
      simple designs for connecting portions of the two halves of the sectional
      dentures might lead to satisfactory results in this case. CONCLUSION: No problems
      have been observed for approximately 6 years after delivery of the acrylic
      sectional dentures for this microstomic patient.

PMID- 16432290
TI  - [Case report of a patient treated with unilateral extension base denture using
      the altered cast technique].
AB  - PATIENT: The patient was a 70-year-old male with a chief complaint of poor
      adaptation of a mandibular unilateral extension base denture. The diagnosis was
      missing teeth of the mandibular bilateral second premolars, the first molars and
      the mandibular left second molar as well as poorly-fitting facing crowns in the
      mandibular bilateral canines and the first premolars. After inserting the facing
      crowns, a metal base denture was constructed using the altered cast technique.
      After 3 years, the metal base denture's masticatory function and appearance were
      successfully achieved. DISCUSSION: It was considered an achievement in this case
      to get maximum support from the residual ridge using the altered cast technique.
      CONCLUSION: The metal base denture was constructed using the altered cast
      technique and successful masticatory function was gained.

PMID- 16432291
TI  - [Case of occlusal reconstruction for severe attrition].
AB  - PATIENT: A 57-year-old female complained of aesthetic disturbance, dysmasesis and
      phonation disorder by attrition. She had severe attrition of almost teeth. To
      avoid metal color exposure and attrition of opposing teeth, hybrid ceramics were
      used for veneered crowns and fixed partial denture. Since the prosthetic
      treatment, the patient wears a night guard to prevent attrition of her teeth and
      prosthesis. DISCUSSION: There has been no specific trouble during the 4-year
      follow-up. CONCLUSION: It is considered that using hybrid ceramics for veneering
      crowns and fixed partial denture and night guard help to prevent the attrition of
      opposing teeth and abrasion of prosthesis.

PMID- 16432292
TI  - [Case report of a patient with bounded missing, treated with removable partial
      denture].
AB  - PATIENT: The patient was a 60-year-old male with the chief complaint of loosening
      of the bridge on the upper right side. The diagnoses of the patient were
      detachment of the bridge (7 6 5 4 3 2 1 | 1) and root fracture (5|). A cobalt
      chromium plate with Mini-SG attachment was used at 4 3 2| to fix the bridge. The
      course of the patient was uneventful five years after the treatment. DISCUSSION:
      Judging from the condition of the detached bridge, the same type of fixed bridge
      was considered too weak to withstand the lateral force. Stabilization of the
      functional occlusion was achieved by using the attachment, followed by good
      clinical results. CONCLUSION: The patient was satisfied with the comfort of the
      removable partial denture with attachment, and good functional results were
      obtained.

PMID- 16432293
TI  - Association of serum reactive oxygen metabolite levels with different
      histopathological types of lung cancer.
AB  - BACKGROUND: Oxygen is required for respiration and the energetic processes that
      enable aerobic life. Costs associated with oxygen use are free radical and
      reactive oxygen metabolite (ROM) formations, which create oxidative stress and
      contribute to various processes including aging, degenerative diseases and
      cancer. Additionally, they may have a role in the pathogenesis of lung cancer
      with different histopathological types. OBJECTIVES: In this study, we aimed to
      investigate the degree of oxidative stress in different types of carcinoma such
      as small cell carcinoma and non-small cell carcinoma, including epidermoid
      carcinoma and adenocarcinoma, and to find out whether the degree of oxidative
      stress shows any difference among them and whether it can be used as an index for
      their differential diagnosis. METHODS: Thirty-eight patients with lung cancer and
      26 healthy persons were included in the study. Of the patients with lung cancer,
      14 had epidermoid carcinoma, 12 adenocarcinoma and 12 small cell carcinoma. Serum
      ROM levels were detected by using an available commercial kit according to the
      manufacturer's instructions. RESULTS: The ROM levels were significantly lower in
      the controls than in the patients (p<0.001). Although all subtypes had
      significantly high ROM levels compared with the controls, the highest
      significance was found in the small cell carcinoma (p<0.001), and then in the
      adenocarcinoma and epidermoid carcinoma (p<0.01 and p<0.01, respectively).
      CONCLUSIONS: In the light of these data, it might be possible to conclude that
      the serum ROM levels increase in patients with different types of lung cancers
      and may be an index parameter for lung cancer. It could be thought that this
      increase, particularly in small cell carcinoma, may contribute to its poor
      progression.

PMID- 16432294
TI  - Clinically equivalent bronchodilatation achieved with formoterol delivered via
      Easyhaler and Aerolizer.
AB  - BACKGROUND: User-friendly devices for the delivery of asthma drugs are needed to
      enhance treatment compliance. Formoterol inhalation powder has been developed to
      Easyhaler multidose powder inhaler to enable the treatment of all asthma
      severities with the same device. OBJECTIVES: This double-blind, double-dummy,
      single- dose, placebo-controlled, cross-over study aimed to demonstrate the non
      inferiority of the bronchodilating effect of formoterol 12 microg delivered via
      Easyhaler versus via Aerolizer. In addition, dose responses following placebo, 12
      microg and 48-microg doses of formoterol via Easyhaler were compared.
      Furthermore, onset and duration of action, and safety of formoterol inhaled using
      the two inhalers were compared. METHODS: Sixty-seven adult asthmatic subjects
      showing >or=15% increase in forced expiratory volume in 1 s (FEV(1)) after short
      acting sympathomimetic inhalation were enrolled and completed the study. The
      study comprised screening and 4 treatment days, with each subject inhaling a
      single 12-mug dose of formoterol via Easyhaler, a 12-microg dose via Aerolizer, a
      48-microg dose via Easyhaler or placebo. Repeat spirometry and vital sign
      measurements were performed for 12 h during treatment days. The primary efficacy
      variable was the area under the flow volume curve (AUC(0-12)) of FEV(1).
      Secondary efficacy variables comprised maximum FEV(1 )(FEV(1max)), forced vital
      capacity (FVC), and the need of rescue medication during the treatment days.
      Safety was evaluated by determining blood pressure, heart rate and the number of
      adverse events (AEs). RESULTS: Results showed the non-inferiority of the
      bronchodilating effect of 12 microg formoterol via Easyhaler compared to
      Aerolizer. The Easyhaler-Aerolizer ratio for AUC(0-12) of FEV(1 )was 0.991 (95%
      confidence interval from 0.969 to 1.013). No statistically significant
      differences emerged for secondary efficacy variables. A statistically significant
      dose response was seen following placebo, 12- and 48-microg doses in FEV(1). No
      safety differences emerged for the 12-microg dose inhaled via Easyhaler or
      Aerolizer, but the incidence of AEs was higher following formoterol 48 microg and
      placebo treatments. CONCLUSIONS: Formoterol delivered via Easyhaler was
      therapeutically equivalent to Aerolizerat the 12-microg dose. The 48-microg dose
      via Easyhaler demonstrated statistically significantly greater bronchodilation
      but showed an increased occurrence of AEs.

PMID- 16432296
TI  - Genistein, a phytoestrogen, attenuates monocrotaline-induced pulmonary
      hypertension.
AB  - BACKGROUND: Pulmonary hypertension is characterized by high pulmonary blood
      pressure, vascular remodeling, and right ventricular hypertrophy. Although recent
      studies suggest that an imbalance between endothelial mediators on pulmonary
      vasculature may contribute to the development of pulmonary hypertension, the
      pathogenesis is not fully understood and the treatment of pulmonary hypertension
      is still unresolved. OBJECTIVE: The purpose of this study was to investigate
      whether genistein, a phytoestrogen derived from soybean, would prevent the
      development of monocrotaline (MCT)-induced pulmonary hypertension in rats.
      Hemodynamic parameters of catheterized rats and morphological feature of lungs
      were evaluated among MCT-treated rats receiving or not receiving genistein.
      Furthermore, examination of expression in endothelial nitric oxide synthase and
      endothelin-1 peptide level was performed. METHODS: Daily supplementation with
      either genistein (0.2 mg/kg) or vehicle was started 2 days prior to a single-dose
      injection of MCT (60 mg/kg). On day 28, rats underwent catheterization, and right
      ventricular hypertrophy and morphological features were assessed. Furthermore,
      endothelial nitric oxide synthase and endothelin-1 were examined by Western blot
      analysis and radioimmunoassay, respectively, in homogenated lungs. RESULTS: In
      rats that received daily supplementation of genistein, mean pulmonary arterial
      pressure was significantly reduced, whereas mean systemic arterial pressure and
      heart rate were unaltered compared with MCT control rats on day 28 after MCT
      injection. Right ventricular hypertrophy, medial wall thickness of pulmonary
      arteries corresponding to the terminal bronchioles, and the degree of neo
      muscularization of more distal arteries were less severe in genistein-treated
      rats. Genistein supplementation improved MCT-induced downregulation of expression
      of endothelial nitric oxide synthase in the lungs. However, endothelin-1 peptide
      levels did not differ among all groups of lungs. CONCLUSIONS: We conclude that
      daily supplementation of genistein potently attenuates MCT-induced pulmonary
      hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling in
      rats. The underlying mechanism responsible for this effect may be partly related
      to the restoration of a decreased expression of endothelial nitric oxide
      synthase.

PMID- 16432295
TI  - Noninvasive positive pressure ventilation in patients with respiratory failure
      due to severe acute pancreatitis.
AB  - BACKGROUND: Patients with acute pancreatitis (AP) who require mechanical
      ventilation have high morbidity and mortality rates. Noninvasive positive
      pressure ventilation (NPPV) delivered through a mask has become increasingly
      popular for the treatment of acute respiratory failure (ARF) and may limit some
      mechanical ventilation complications. OBJECTIVES: The purpose of this
      retrospective, observational study was to evaluate our clinical experience with
      the use of NPPV in AP patients with ARF. METHODS: From 1997 to 2003, we
      documented clinical data, gas exchange and outcome of the 62 AP patients admitted
      to our intensive care unit. Patients who benefited from NPPV (success) were
      compared with those who failed (intubated). RESULTS: Twenty-nine patients were
      intubated at admission and 5 did not develop ARF. Of the 28 patients treated with
      NPPV, 15 were not intubated (54%). Both groups had a similar PaO(2)/FiO(2) ratio
      (142 +/- 21 vs. 133 +/- 20; p = 0.127) and severity of illness (Ranson and
      Balthazar scores). Presence of atelectasis, bilateral alveolar infiltrates and
      abdominal distension were associated with failure of NPPV. Oxygenation improved
      and respiratory rate decreased significantly only in the success group.
      Additionally, the length of stay at the intensive care unit was significantly
      lower in the success group. CONCLUSION: NPPV is feasible and safe to treat ARF in
      selected patients with AP who require ventilatory support.

PMID- 16432297
TI  - Systemic immunological response to exercise in patients with chronic obstructive
      pulmonary disease: what does it mean?
AB  - Chronic obstructive pulmonary disease (COPD) is no longer seen as a pulmonary
      disease, but is increasingly associated with systemic effects with important
      clinical relevance. Systemic immunological changes in COPD patients are
      characterized by an increased number of circulating inflammatory cells,
      functional changes of the inflammatory cells, elevated plasma levels of
      cytokines, and oxidative stress. Physical exercise induces an abnormal systemic
      inflammatory and oxidative response in COPD patients, which is seen in both the
      circulation and the peripheral muscles. Although mechanisms and consequences of
      these effects are not yet fully understood, they could be harmful in COPD
      patients by inducing damage or functional changes in, for example, skeletal
      muscles. Whether these changes of the immune system can also affect the
      susceptibility to infections in these patients is unknown. The concept of COPD as
      a systemic rather than only a pulmonary disease also opens new perspectives on
      the development for new therapeutic interventions. The effects of new
      antioxidative and anti-inflammatory agents are investigated. A better
      understanding of the complexity of the systemic effects will aid the development
      of new therapies and management strategies for patients with COPD.

PMID- 16432298
TI  - Pulmonary echinococcosis with multiple nodules mimicking metastatic lung tumor in
      chest radiography.

PMID- 16432299
TI  - Evolution of the amygdala: new insights from studies in amphibians.
AB  - The histology of amphibian brains gives an impression of relative simplicity when
      compared with that of reptiles or mammals. The amphibian telencephalon is small
      and contains comparatively few and large neurons, which in most parts constitute
      a dense periventricular cellular layer. However, the view emerging from the last
      decade is that the brains of all tetrapods, including amphibians, share a general
      bauplan resulting from common ancestry and the need to perform similar vital
      functions. To what extent this common organization also applies to higher brain
      functions is unknown due to a limited knowledge of the neurobiology of early
      vertebrates. The amygdala is widely recognized as a brain center critical for
      basic forms of emotional learning (e.g., fear conditioning) and its structure in
      amphibians could suggest how this capacity evolved. A functional systems approach
      is used here to synthesize the results of our anatomical investigations of the
      amphibian amygdala. It is proposed that the connectivity of the amphibian
      telencephalon portends a capacity for multi-modal association in a limbic system
      largely similar to that of amniote vertebrates. One remarkable exception is the
      presence of new sensory-associative regions of the amygdala in amniotes: the
      posterior dorsal ventricular ridge plus lateral nuclei in reptiles and the
      basolateral complex in mammals. These presumably homologous regions apparently
      are capable of modulating the phylogenetically older central amygdala and allow
      more complex forms of emotional learning.

PMID- 16432300
TI  - Malignant insulinoma in ectopic pancreatic tissue.
AB  - BACKGROUND: Both ectopic pancreatic tissue and malignant insulinoma are rare. We
      encountered the combination of these rare entities in a patient demonstrating
      hypoglycemic symptoms. METHOD: A patient with episodic hypoglycemia, non
      suppressed serum insulin levels, positive fasting test and a positive
      localization on both ultrasound and somatostatin receptor scintigraphy by (111)I
      labelled octreotide, was operated and investigated. RESULTS: (111)I-labelled
      octreotide-guided surgery was performed and a tumor adjacent to the ligament of
      Treitz was extirpated. Follow-up was uneventful. Histopathology revealed a
      malignant insulinoma. The patient is currently under close surveillance.
      CONCLUSION: The rare combination of an insulinoma in ectopic pancreatic tissue,
      where the usual diagnostic endoscopic ultrasound revealed an extrapancreatic
      mass, is described. This was followed by a positive somatostatin receptor
      scintigraphy, enabling both radio-guided surgery and future treatment of
      developing recurrent disease or metastases.

PMID- 16432301
TI  - Neurological deficits in the life and works of Frida Kahlo.
AB  - World-famous Mexican painter Frida Kahlo is an impressive example of an artist
      whose entire life and creativity were extremely influenced by chronic, severe
      illness. Many of her best-known works depict her physical and mental suffering.
      She was one of those very uncommon artists who dared to show their nude, sick
      body. This article describes biographical events and works of Frida Kahlo that
      are closely related to neurology: congenital anomaly (spina bifida),
      poliomyelitis, spine injury, neuropathic pain.

PMID- 16432302
TI  - The role of matrix metalloproteinase 9 in early neurological worsening of acute
      lacunar infarction.
AB  - The involvement of matrix metalloproteinases (MMPs) in ischemic-stroke-induced
      inflammatory response has recently been suggested; however, the relationship
      between MMPs and stroke progression has not been evaluated. We investigated the
      role of MMPs in neurological worsening of acute lacunar infarction. Forty-nine
      consecutive patients with an acute lacunar infarction (as defined by clinical and
      MRI criteria within 48 h after stroke onset) were evaluated. Clinical,
      biochemical, rheological, inflammatory and other parameters were compared between
      progressive and nonprogressive groups. Among the variables, only inflammatory
      parameters, including MMP-9 and erythrocyte sedimentation rate, were associated
      with neurological worsening of acute lacunar infarction (p<0.05). These results
      suggest that the inflammatory process could play an important role in early
      neurological worsening of acute lacunar infarction.

PMID- 16432303
TI  - Examination by near-infrared spectroscopy for evaluation of piano performance as
      a frontal lobe activation task.
AB  - The purpose of this study was to reveal the activation of the frontal lobe in
      piano performance by the use of near-infrared spectroscopy. Participants
      wereseven healthy volunteer music college students. The results of the
      examination showed a tendency towards an increase in total hemoglobin volume over
      a wider area in the frontal part of the brain during an appropriate piano task
      compared with an easy piano task or the Keio version of the Wisconsin Card
      Sorting Test. The results suggest that piano performance is recognized as a
      frontal lobe-activating task and that performance of an appropriate piano task
      can be expected to elicit wider activation of the frontal lobe than an easy one.

PMID- 16432304
TI  - The effect of phenotype on mechanical stretch-induced vascular smooth muscle cell
      apoptosis.
AB  - The present study evaluated mechanical stretch-induced apoptosis in swine
      vascular smooth muscle cells (VSMC) of different phenotypes. We demonstrated that
      differentiated VSMC express a greater level of Bcl-2-associated death factor
      (BAD) and have a significant cell loss when exposed to mechanical stretch (10%
      elongation, 1 Hz) for 24 h. We further demonstrated that apoptosis was
      significantly increased only in differentiated VSMC exposed to mechanical
      stretch. To test the hypothesis that the intracellular level of BAD in VSMC
      determines its response to mechanical stretch-induced apoptosis, we examined
      whether BAD expression was upregulated by mechanical stretch-induced apoptosis
      and was associated with the increase in the apoptosis level of differentiated
      VSMC. When exposed to mechanical stretch, the expression of BAD in differentiated
      VSMC was elevated at 1 h and remained at higher levels during the application of
      stretch (24 h). In contrast, Bcl-2 expression was suppressed during the
      application of stretch. Moreover, the proapoptotic function of BAD was inhibited
      by overexpression of Bcl-2 through transient transfection of VSMC with pCEP4-Bcl
      2 or incubation of VSMC with vascular epithelial growth factor. These results
      suggest that mechanical stretch-induced VSMC apoptosis is phenotype dependent.
      The higher levels of apoptosis of differentiated VSMC upon mechanical stretch
      were, at least in part, dependent on their intrinsic level of BAD.

PMID- 16432306
TI  - Good mathematical practice: simulation of the hemostatic-thrombotic mechanism, a
      powerful tool but one that must be used with circumspection.

PMID- 16432305
TI  - Biomechanical strength of reconstruction plates when used for medial support of
      MED-El cochlear implants: implications for diagnostic MRI.
AB  - PURPOSE: It is hypothesized that a mesh reconstruction plate designed to fit a
      cochlear implant (CI) internal device will provide immediate structural support
      to the site of the implant and that this strength far exceeds the forces induced
      by a 1.5-tesla MRI. PROCEDURES: Human calvarial specimens were drilled and plated
      with reconstruction mesh. Force was applied until failure was reached. RESULTS:
      Mean maximum force, mean force to first failure and mean displacement measures
      for group 1 (resorbable mesh, n = 10) were 302.9 N, 283.0 N and 3.05 mm,
      respectively. The mean maximum force for group 2 (0.4-mm titanium mesh, n = 10)
      and group 3 (0.6-mm titanium mesh, n = 8), were 121.3 and 234.0 N, respectively.
      Mean force of first failure was 92.0 N for group 2 and 164.8 N for group 3.
      CONCLUSIONS: The force required for failure of the mesh is significantly greater
      than the 0.17 N exerted on a CI magnet by a 1.5-tesla MRI scan.

PMID- 16432307
TI  - Towards virtual coagulation.

PMID- 16432308
TI  - Mathematical modeling and computer simulation in blood coagulation.
AB  - Over the last two decades, mathematical modeling has become a popular tool in
      study of blood coagulation. The in silico methods were able to yield interesting
      and significant results in the understanding of both individual reaction
      mechanisms and regulation of large sections of the coagulation cascade. The
      objective of this paper is to review the development of theoretical research in
      hemostasis and thrombosis, to summarize the main findings, and outline problems
      and possible prospects in the use of mathematical modeling and computer
      simulation approaches. This review is primarily focused on the studies dealing
      with: (1) the membrane-dependent reactions of coagulation; (2) regulation of the
      coagulation cascade, including effects of positive and negative feedback loops,
      diffusion of coagulation factors, and blood flow.

PMID- 16432309
TI  - Demonstration of a threshold response in a proteolytic feedback system: control
      of the autoactivation of factor XII.
AB  - Mathematical analysis of positive feedback loops in proteolytic systems has
      previously suggested that when the active enzymes are subject to inhibitory
      control these systems will exhibit threshold behavior. This is demonstrated in
      the present study, for the autolytic activation of factor XII in the presence of
      a contact activator and an irreversible inhibitor of factor XIIa. The threshold
      between the two system states - complete factor XII activation, or complete
      stability - is dependent on the kinetic balance between the catalytic rate of
      autoactivation and rate of enzyme (factor XIIa) inhibition. Activation of the
      system can be brought about by either increasing the catalytic rate (in this
      study, by using more potent contact-activation conditions), or by lowering the
      enzyme inhibition rate. Previous mathematical work predicted complete stability
      in a positive-feedback system that is below threshold, and this has been
      experimentally confirmed.

PMID- 16432310
TI  - Stochastic modeling of blood coagulation initiation.
AB  - A kinetic Monte Carlo simulation was developed using the deterministic reaction
      network developed by the Mann laboratory for tissue-factor (TF)-initiated blood
      coagulation. The model predicted thrombin dynamics in recalcified whole blood (3
      fold diluted) pretreated with convulxin (platelet GPVI activator) and picomolar
      levels of TF (0-14 pM). The model did not accurately predict coagulation times at
      low TF (0-0.7 pM). The simulation revealed that approximately 0.2 pM TF was the
      critical concentration to cause 50% of reactions containing 3-fold diluted whole
      blood to reach a clotting threshold of 0.05 U/ml thrombin by 1 h. Simulations of
      1 nl of blood (5 pM TF) revealed small stochastic variations in thrombin
      initiation time, while 16.6 pl simulations were highly stochastic at this level
      of TF (50 molecules/16.6 pl). Further experiment and simulation will require
      evaluation of mechanisms of coagulation kinetics at subpicomolar levels of TF.

PMID- 16432311
TI  - Coagulation under flow: the influence of flow-mediated transport on the
      initiation and inhibition of coagulation.
AB  - A mathematical model of intravascular coagulation is presented; it encompasses
      the biochemistry of the tissue factor pathway, platelet activation and deposition
      on the subendothelium, and flow- and diffusion-mediated transport of coagulation
      proteins and platelets. Simulation experiments carried out with the model
      indicate the predominant role played by the physical processes of platelet
      deposition and flow-mediated removal of enzymes in inhibiting coagulation in the
      vicinity of vascular injury. Sufficiently rapid production of factors IXa and Xa
      by the TF:VIIa complex can overcome this inhibition and lead to formation of
      significant amounts of the tenase complex on the surface of activated platelets
      and, as a consequence, to substantial thrombin production. Chemical inhibitors
      are seen to play almost no (TFPI) or little (AT-III and APC) role in determining
      whether substantial thrombin production will occur. The role of APC is limited by
      the necessity for diffusion of thrombin from the site of injury to nearby
      endothelial cells to form the thrombomodulin-thrombin complex and for diffusion
      in the reverse direction of the APC made by this complex. TFPI plays an
      insignificant part in inhibiting the TF:VIIa complex under the conditions studied
      whether its action involves sequential binding of TFPI to Xa and then TFPI:Xa to
      TF:VIIa, or direct binding of TFPI to Xa already bound to the TF:VIIa complex.

PMID- 16432312
TI  - A model for the formation and lysis of blood clots.
AB  - Both biochemical and mechanical factors have to be taken into account if a
      meaningful model for the formation, growth, and lysis of clots in flowing blood
      is to be developed. Most models that are currently in use neglect one or the
      other of these factors. We have previously reported a model [J Theoret Med
      2003;5:183-218] that we believe is a step in this direction, incorporating many
      of the crucial biochemical and rheological factors that play a role in the
      formation, growth, and lysis of clots. While this model takes into account the
      extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here,
      we discuss some of the general issues with respect to mathematical modeling of
      thrombus formation and lysis, as well as specific aspects of the model that we
      have developed.

PMID- 16432313
TI  - The effect of convective flows on blood coagulation processes.
AB  - Two mathematical models of clot growth in the fluid flows have been considered.
      The first one is the model of embolus growth in a wall-adjacent flow. The effect
      of hydrodynamic flows on proceeding chemical reactions and the backward effect of
      the growing clot on the flow are taken into account. The growing thrombus is
      assumed to be porous and having low permeability, that is in good agreement with
      experimental data. The exact solutions determining the distribution of a fluid
      velocity close to the embolus have been used. Numerical analysis of these
      solutions have demonstrated that hydrodynamic flows can essentially affect the
      processes of blood coagulation, and consequently on the clot structure. Their
      presence might lead to the destruction of chemical fronts having a cylindrical
      symmetry and formation of the so-called chemical spots. The second model
      describes the initial stage of thrombus growing in the hemorrhage into a natural
      internal space. It permits accounting for vessel geometry and provides studying
      the effects of geometric parameters on fluid flows and coagulation processes. The
      process of thrombus growth is shown to depend on the ratio of typical values of
      blood velocity in the vessel and rate of chemical reactions.

PMID- 16432314
TI  - Blood coagulation and propagation of autowaves in flow.
AB  - This study analyses the effect of flow and boundary reactions on spatial
      propagation of waves of blood coagulation. A simple model of coagulation in
      plasma consisting of three differential reaction-diffusion equations was used for
      numerical simulations. The vessel was simulated as a two-dimensional channel of
      constant width, and the anticoagulant influence of thrombomodulin present on the
      undamaged vessel wall was taken into account. The results of the simulations
      showed that this inhibition could stop the coagulation process in the absence of
      flow in narrow channels. For the used mathematical model of coagulation this was
      the case if the width was below 0.2 mm. In wider vessels, the process could be
      stopped by the rapid blood flow. The required flow rate increased with the
      increase of the damage region size. For example, in a 0.5-mm wide channel with 1
      mm long damage region, the propagation of coagulation may be terminated at the
      flow rate of more than 20 mm/min.

PMID- 16432315
TI  - Smoking and wound healing problems in reduction mammaplasty: is the introduction
      of urine nicotine testing justified?
AB  - We sought to prove a significant relationship between cigarette smoking and wound
      healing problems in reduction mammaplasty patients, to show the effect of
      stopping smoking before the procedure, and to justify the implementation of urine
      nicotine testing preoperatively. One hundred and seventy-three consecutive
      patients aged 16 to 67 years underwent bilateral reduction mammaplasty in our
      institution over 26 months. Patients were advised to stop smoking at least 4
      weeks prior to surgery. Records were reviewed and smoking habits reconfirmed via
      telephone. Wound problems were registered when intervention was necessary.
      Smokers made up 38.5% of the cases. Wound healing problems showed statistical
      significance (P < 0.05) between smokers (55.4%) and nonsmokers (33.7%). More than
      75% of smokers admitted denying smoking within 4 weeks of surgery. Trend analysis
      revealed a significant association of wound healing problems for those who
      stopped longer than 4 weeks (33.3%), those who stopped less than 4 weeks (52.6%),
      and those who persisted until the operation (67.7%). Smoking increased wound
      healing problems after bilateral reduction mammaplasty. The introduction of
      compulsory urine nicotine testing at the preadmission clinic and prior to the
      operation will provide objective verification of patients' smoking history,
      minimize morbidity, and enable healthcare cost savings.

PMID- 16432317
TI  - Treatment of complex below-the-elbow gunshot wounds.
AB  - Firearm injuries, many of which involve the hand, wrist, or forearm, pose a
      serious public health concern in the United States in both medical and economic
      terms. Despite the preponderance of low-velocity weapons, complex below-the-elbow
      gunshot injuries are commonly seen. A successful approach to these patients
      requires efficient treatment and early initiation of rehabilitation.
      Unfortunately, this goal is often not met because of multiple factors including
      wound infections, the need to coordinate multiple surgical specialties, long
      hospital stays, and delayed definitive reconstruction. At our institution, the
      plastic surgery hand service is able to treat all aspects of below-the-elbow
      trauma. A protocol of early aggressive debridement and skeletal stabilization,
      with definitive reconstruction within 1 week of injury, is used. We
      retrospectively reviewed all complex below-the-elbow gunshot injuries treated by
      the senior author between 1996 and 2003. Eighteen such patients were identified.
      All limbs were salvaged and all patients regained functional use of the
      extremity. There was no incidence of wound infection. The average length of
      inpatient stay was 8.9 days (median, 7 days). The use of this protocol by a
      single surgical specialty allows efficient reconstruction, short hospital stays,
      and early initiation of rehabilitation.

PMID- 16432316
TI  - Use of the lateral intercostal perforator-based pedicled abdominal flap for upper
      limb wounds from severe electrical injury.
AB  - BACKGROUND: Upper-extremity wounds can be covered with a variety of flaps.
      However, pedicled distant flaps still have a place in treatment, especially in
      the early stages of wound restoration after a severe electrical injury. The
      purpose of this clinical study was to present the use of the pedicled abdominal
      flap, using the blood supply of the lateral intercostal perforator vessel, to
      cover defects caused by severe electrical injury. METHODS: Between 2003 and 2005,
      6 cases of deep burn wounds were treated with a lateral intercostal perforator
      based pedicled abdominal cutaneous flap, with the blood supply originating from
      the lateral perforator branches of the seventh to 10th intercostal arteries. This
      flap was used to repair deep burn wounds on the elbow, forearms, and hands that
      were the result of severe electrical injuries. RESULTS: Flaps were harvested in
      sizes ranging from 16 cm x 12 cm to 9 cm x 7 cm. The pedicle was separated from
      18 to 21 days after the operation. Five flaps survived entirely. The sixth
      underwent marginal necrosis (1.5 cm x 3 cm) at the distal portion of the flap
      because flap cutting exceeded the paraumbilical line. Results were cosmetically
      satisfactory for all patients. CONCLUSIONS: This flap is suitable for covering
      defects in hands, forearms, and elbows. The procedure was performed easily,
      safely, and reliably, and the flap has several advantages over other commonly
      used techniques for upper-limb wounds from severe electrical injury. We recommend
      this flap as the treatment of choice.

PMID- 16432318
TI  - Kirschner-wire fixation for postburn flexion contracture deformity and
      consequences on articular surface.
AB  - Kirschner-wire (K-wire) fixation for 3-6 weeks is an approved method for
      stabilization of the fingers after the release of flexion contracture deformity.
      On the other hand, articular surface damage in small joints due to pin fixation
      is still a topic of debate. Reports claiming permanent joint destruction due to
      this procedure exist in the literature. To clarify this doubt, a prospective
      study was carried out in 72 patients with flexion contracture of the hand
      fingers. After the surgical release of the deformity, immobilization of the
      interphalangeal (IP) and metacarpophalangeal (MCP) joints was carried out with K
      wire fixation for 3 weeks. Clinical evaluation of the patients was accomplished
      with total active motion (TAM), grip, and pinch force measurements, whereas
      magnetic resonance (MR) and radionuclide imaging were used as radiodiagnostic
      tools. Mean follow-up period of the patients was 32 months. Satisfactory results
      were obtained in terms of functional and esthetic aspects. Evaluation of the data
      derived from the clinical and radiologic measurements revealed no permanent
      articular surface damage. K-wire fixation was documented to be an invaluable
      therapeutic approach not only to prevent recurrence of the contracture deformity
      but also to stabilize the skin graft effectively. This technique was concluded to
      provide effective immobilization without permanent articular damage.

PMID- 16432319
TI  - Efficacy of a percutaneous A1 pulley release technique with identification of
      anatomic differences between genders.
AB  - BACKGROUND: This cadaver study investigates the efficacy and safety of the Biomet
      knife and technique for percutaneous A1 pulley release. We also evaluate the
      anatomic relationship between specific palmar surface landmarks and relevant
      underlying structures and identify differences between genders. METHODS: Eighty
      percutaneous A1 pulley releases, excluding the thumb, were performed on 20 fresh
      human cadaver hands (10 male, 10 female). RESULTS: Complete release was obtained
      in 60 of 80 fingers. Success rates for each surgeon improved markedly as the
      study progressed. There were no significant differences between males and females
      regarding the distance between a standardized incision site and the proximal edge
      of the A1 pulley. CONCLUSIONS: A learning curve exists for percutaneous A1 pulley
      release using the Biomet knife and technique. The extended distal palmar crease
      is a reasonable incision site for percutaneous release of the index, middle, and
      ring A1 pulleys in both men and women as the A1 pulley begins just distal to this
      surface landmark.

PMID- 16432320
TI  - Long-term results of midcarpal arthrodesis in the treatment of scaphoid nonunion
      advanced collapse (SNAC-Wrist) and scapholunate advanced collapse (SLAC-Wrist).
AB  - Outcome evaluation of midcarpal arthrodesis in the treatment of scaphoid nonunion
      advanced collapse (SNAC-wrist) and scapholunate advanced collapse (SLAC-wrist).
      PURPOSE: Scaphoid nonunion or scapholunate ligament instability results in carpal
      collapse and subsequent arthrosis. These conditions, termed SLAC-wrist and SNAC
      wrist, are the most common patterns of arthrosis in the wrist. The purpose of
      this retrospective study was the evaluation of functional outcomes following
      midcarpal arthrodesis and of patients' satisfaction with these outcomes. METHODS:
      Forty-nine patients were reexamined at a mean follow-up time of 47 months. Active
      range of motion (AROM) was verified with a goniometer; grip strength was measured
      with a JAMAR-Dynamometer II. Pain was evaluated by a visual analogue scale from
      zero to 100 (VAS 0-100) for stress and under resting conditions. Patients' upper
      extremity functioning was captured with the Disabilities of the Arm, Shoulder and
      Hand (DASH) questionnaire. Radiographic evaluation of bony consolidation was
      verified by conventional x-ray. RESULTS: Postoperative AROM was 56% and grip
      strength was 76% compared with the contralateral side. The DASH score was 29
      points. Pain relief was 34% at rest and 31% after stress. Forty-five patients
      demonstrated bony consolidation in x-ray control. Six patients (12%) further
      required a total arthrodesis of the wrist because of pain or absence of bony
      consolidation. CONCLUSION: Our data demonstrate that midcarpal arthrodesis is a
      reliable procedure for treating SLAC- and SNAC-wrists in stages II and III and,
      furthermore, one which preserves some range of motion. Total wrist fusion should
      only be used in exceptional circumstances.

PMID- 16432321
TI  - Relationship between peripheral nerve decompression and gain of pedal sensibility
      and balance in patients with peripheral neuropathy.
AB  - This was an initial exploratory study to determine if decompression of the 4
      medial ankle tunnels (neurolysis of the tibial, medial and lateral plantar, and
      calcaneal nerves) could lead to improved foot sensibility, increased
      proprioception and balance, and decreased falls in a population of patients with
      impaired lower extremity sensation. Fourteen patients with peripheral neuropathy
      were included in this study. Seventy-one percent of patients were females.
      Average age was 67 years. All patients were evaluated preoperatively and
      postoperatively to assess their lower extremity sensibility, as well as their
      ability to stand still, maintaining their balance with their eyes open and then
      closed, which is defined as "sway." Lower extremity sensibility was measured with
      the Pressure-Specified Sensory Device (PSSD), which evaluates 1- and 2-point
      discrimination for the pulp of the big toe and medial heel. The MatScan
      Measurement System measured each patient's sway. Neuropathy was the result of
      diabetes in 72% of patients, a combination of diabetes and hypothyroidism in 7%,
      chemotherapy in 7%, and idiopathic in 14%. Eight patients underwent peripheral
      nerve decompression on 1 lower extremity, whereas 6 patients underwent bilateral
      lower extremity peripheral nerve decompression. Mean toe and heel sensibility
      improved 9% and 7%, respectively, in the unilateral group, whereas the bilateral
      group experienced an improvement in mean toe and heel sensibility of 42% (P =
      0.02) and 32%, respectively. Preoperative and postoperative sway comparison in
      the unilateral group revealed a reduction in sway with eyes open and eyes closed
      by 5% and 31%, respectively. Comparison of preoperative and postoperative sway in
      the bilateral group showed a reduction with eyes open and eyes closed by 23% and
      145% (P = 0.05), respectively. This initial study suggests that there may be
      benefit from bilateral lower extremity peripheral nerve decompression in helping
      improve pedal sensibility and balance within the peripheral neuropathy patient
      population, although further investigation with a larger sample size is warranted
      to further evaluate these preliminary findings.

PMID- 16432322
TI  - Perineum reconstruction with pedicled anterolateral thigh fasciocutaneous flap.
AB  - Eighteen pedicled anterolateral thigh perforator island flaps were used for
      complex perineal reconstructions between May 2003 and May 2005. The patients'
      average age was 48.6 years (range, 32 to 64 years), and the average follow-up
      period was 8 months (range, 2 to 13). In 7 cases, the perforator was
      septocutaneous and in 11 it was intramuscular. The application of the pedicled
      anterolateral thigh fasciocutaneous flap is described perineum reconstruction.
      The size of the perineum defects ranged from 6 x 9 cm to 16 x 17 cm, and the size
      of the transferred flap ranged from 8 x 11 cm to 18 x 20 cm. All flaps survived.
      One patient developed minor wound dehiscence in the posterior aspect of the
      perineal wound because of fecal contamination and skin maceration. The esthetic
      appearance of the reconstructed perineum was good. Despite a variable vascular
      anatomy that can give rise to some surgical challenge in raising the flap, the
      authors conclude that this is a safe and reliable flap for perineal
      reconstruction.

PMID- 16432323
TI  - Never say no to a damaged muscle: the applications of previously damaged
      pectoralis major and latissimus dorsi muscles for chest wall reconstruction.
AB  - The nondamaged latissimus dorsi and pectoralis major muscles are widely reported
      in the literature as being the most frequently used for chest wall
      reconstruction. In this study, we report a series of 9 patients with full
      thickness chest wall defects who underwent reconstruction with previously damaged
      latissimus dorsi or pectoralis major muscles. Nine patients underwent chest wall
      reconstruction over a period of 3 years using previously damaged latissimus dorsi
      or pectoralis major muscles. The thoracic defect was posttraumatic in 3 patients
      and post-tumor resection in 6 patients. Three patients had previous radiation
      therapy. In 8 cases, the full-thickness chest wall defects were completely
      closed. The only failure encountered was in one patient who had a long lasting
      fistula. The proximal based island flap that was inserted into the tract showed
      good vascular supply and viability; however, it did not solve the clinical
      problem. Keeping in mind the basic rule of medicine ("Primum Non Nocere") and a
      thorough knowledge of the surgical anatomy of these muscles are essential for the
      successful application of these previously damaged muscles for chest wall
      reconstruction.

PMID- 16432324
TI  - Medial plantar artery (instep flap) flap.
AB  - Provision of sensation to the weightbearing surface of the heel is very vital in
      the sensate foot. Hence, resurfacing the weightbearing surface of the heel
      requires provision of stable skin cover and sensation. We have many options to
      fulfill the above requirements. Skin of the instep area can be raised as an
      island fasciocutaneous flap based on medial plantar vessels, with the branch of
      medial plantar nerve supplying the instep skin to provide the sensation. Medial
      plantar artery (instep) flap provides similar tissue with sensation and reaches
      the posteriormost part of the weightbearing surface of the heel with ease. We
      present in this article the relevant surgical anatomy, technique, and the
      clinical experience of 12 patients.

PMID- 16432325
TI  - A side-by-side prospective study of intense pulsed light and Nd:YAG laser
      treatment for vascular lesions.
AB  - Recently, lasers and light systems are used more for the treatment of vascular
      lesions due to their noninvasiveness, ease of use, and short recovery time. This
      side-by-side prospective study compares results, satisfaction, and complications
      after intense pulsed light (IPL) and Nd:Yag laser treatment of small vascular
      lesions. Twenty-five patients with telangiectases, leg veins, or cherry angiomas
      underwent treatment of the same category of lesion in the same area. One year
      after completing treatment, patients were asked to report their satisfaction
      level after comparing digital photos before and after treatment; 72% felt they
      had good to excellent results after Nd:Yag treatment, while only 48% felt the
      same after IPL. The most common side effect after Nd:Yag was hyperpigmentation.
      Satisfaction level was significantly higher after Nd:Yag than after IPL. Patients
      with telangiectases, cherry angiomas, or leg veins <1 mm were more satisfied
      after IPL, while those with leg veins >1 mm were more satisfied after Nd:Yag.
      Overall, satisfaction with treatment of vascular lesions was greater with Nd:Yag
      although this method was more painful.

PMID- 16432326
TI  - Availability of end-to-side arterial anastomosis to the external carotid artery
      using short-thread double-needle microsuture in free-flap transfer for head and
      neck reconstruction.
AB  - We seldom have difficulties in the selection of appropriate recipient arteries
      for microvascular free flap transfer in the head and neck region because many
      sizable branches (branch artery) of the external carotid artery (ECA) or
      subclavian artery are available. However, we occasionally encountered the lack of
      an appropriate recipient artery, especially in secondary reconstruction or
      reconstruction following the extensive ablation of recurrent cancer. For these
      challenging cases, we have used end-to-side arterial anastomosis directly to the
      ECA. Between July 1997 and December 2004, end-to-side anastomosis of the flap
      artery to the ECA was employed in 16 cases. The reason for its use included the
      marked size discrepancy between the jejunal artery and branch artery in 4 jejunal
      transfer cases, the lack of 2 appropriate recipient arteries for double free flap
      transfers in 1 case, and the lack of an available branch artery as a recipient
      due to poor regional conditions in 11 cases. Fifteen of 16 flaps underwent an
      uneventful postoperative course, except 1 whose flap artery was pressed by the
      submandibular gland and sustained thrombosis 3 days postoperatively. In this
      case, however, the flap survived perfectly after prompt thrombectomy and
      reanastomosis. Eventually, all 16 flaps survived completely. We reconfirmed the
      availability of end-to-side anastomosis to the ECA when a suitable branch artery
      is not available. Although end-to-side anastomosis to the ECA is laborious
      compared with end-to-end anastomosis, our newly developed short-thread double
      needle microsuture combined with the back-wall-first technique helps to ensure
      easier anastomosis. Using this device, because all stitches are carried from
      inside the vessel to outside, the surgeon can place the first stitch at any point
      on the posterior wall and advance the next suture to the preferred site of the
      previous suture, and suturing can be performed more safely even in cases where
      the tunica intima is separated from the tunica media due to arteriosclerosis,
      previous irradiation, or surgery.

PMID- 16432327
TI  - Skin regeneration for giant pigmented nevus using autologous cultured dermal
      substitutes and epidermis separated from nevus skin.
AB  - We have developed a modality of treatment of giant pigmented nevus of intradermal
      type. This method involves application of autologous cultured dermal substitute
      (CDS), followed by grafting of epidermis separated from the patient's nevus skin.
      To prepare the wound bed, autologous CDS was applied onto a full-thickness skin
      defect after complete excision of the nevus. The excised nevus skin was preserved
      for 1 week, after which the epidermis was separated from the nevus skin by
      enzymatic treatment with dispase. The epidermis thus obtained was grafted onto
      the resulting wound bed. This procedure was used to treat a giant pigmented nevus
      on a 7-year-old patient. The grafted region was soft with good tone 1 year after
      epidermis grafting. These results indicate that the present method can achieve
      complete excision of giant nevus, with esthetically acceptable results, although
      it requires careful monitoring for a long time.

PMID- 16432328
TI  - Dermal neoformation during partial-thickness skin wound healing.
AB  - We have previously described the healing process of full-thickness skin wounds as
      documented by alkali water cell-maceration scanning electron microscopy. In this
      study, we examined partial-thickness skin wounds. The present study provided a 3
      dimensional visualization of the microarchitecture of the dermal neoformation
      process in partial-thickness wounds and proved that the development of the
      papillary dermis proceeded from the stump of the fibrous root sheath and is
      coupled with the epidermis advancing from the transected hair follicle. The
      present findings confirm our previously described unit theory as the
      epithelialization proceeds by forming an "epithelization unit."

PMID- 16432329
TI  - The effect of twisting on perforator flap viability: an experimental study in
      rats.
AB  - Perforator flaps increasingly find acceptance and use in the field of
      reconstructive surgery due to their decreased donor-site morbidity and increased
      like-tissue coverage. Nevertheless, they are more prone to vascular compromise,
      especially when the meticulous technique they require is not employed. Pedicle
      twisting is a condition occasionally encountered in flap procedures, sometimes
      inadvertently, sometimes inevitably. In this study, circulatory comprise induced
      by twisting of the pedicle on a true perforator flap in a rat model is
      investigated.Thirty-eight Wistar-Albino rats were randomized into 4 groups, and
      cranial epigastric artery true perforator flaps were elevated on a single
      perforator. The flaps were returned as they were in the control group (n = 9),
      and with 90 degrees , 180 degrees , and 270 degrees of torsion in groups 2 (n =
      9), 3 (n = 10), and 4 (n = 10), respectively. The flaps were evaluated by their
      flap survival area, weight, and histopathological appearance by the end of the
      first week. The mean flap survival ratios for groups 1, 2, 3, and 4 were 97.78 +/
      4.41%, 72.22 +/- 44.10%, 73.50 +/- 30.46%, and 30 +/- 30.18% (mean +/- SD),
      respectively. The degree of degenerative changes in group 4 was found to be
      statistically significant (P < 0.016).Our histopathological examinations indicate
      that vascular compromise was moderate in group 3 and severe in group 4. Our
      findings suggest that under normal conditions, the pedicle of a true perforator
      flap must not be twisted more than 180 degrees .

PMID- 16432330
TI  - Successful revascularization following near-complete amputation of the tongue.
AB  - Successful salvage of the tongue following near or complete traumatic amputation
      is a rare event. We now report only the second reported successful case of a
      revascularization of a near or complete amputation of the tongue while in the
      setting of massive facial trauma. Microscopic revascularization was performed
      utilizing the left lingual artery and right lingual vein, and despite a prolonged
      ischemic period, a functional tongue was salvaged. Our patient demonstrated that
      the tongue can survive up to 16 hours of ischemia. The successful replantation
      also suggests that arterial blood flow through a single lingual artery and a
      contralateral single vein may be adequate to perfuse the entire mobile tongue,
      despite the previously thought avascular median fibrous septum. Tongue
      revascularization can be performed in the setting of massive facial trauma and
      large-volume fluid resuscitation.

PMID- 16432331
TI  - Vacuum-assisted closure (VAC Therapy) and the risk of fluid loss in acute trauma.

PMID- 16432332
TI  - Vastus medialis muscle flap and hemi V-Y skin flap for knee extensor and soft
      tissue reconstruction.
AB  - Simultaneous reconstruction of extensor mechanism and skin defect of the knee
      joint is a difficult problem. We present a case of a 55-year-old man with loss of
      patella and 9 x 6 cm skin defect after total patellectomy for infected open
      patellar fracture. Vastus medialis muscle flap and hemi V-Y skin flap were
      elevated. Vastus medialis muscle flap was advanced and sutured to the remaining
      patellar tendon. Hemi V-Y skin flap covered the skin defect. The wound healed
      uneventfully. After a follow-up period of 30 months, active range of motion of
      the knee joint is 0-120 degrees, and extension strength of the knee joint is [4]
      in a manual muscle test. He can stand on his right leg without any assistance.
      The combination of vastus medialis flap and hemi V-Y skin flap is a valuable
      option in knee reconstruction after total patellectomy.

PMID- 16432334
TI  - Refractory eczematous dermatitis associated with retained suture material.
AB  - We present a patient who developed a cutaneous-id reaction and eczematous
      dermatitis related to a residual Prolene suture following excision of
      dermatofibrosarcoma protuberans. Following a wider excision of the site, with
      removal of the retained suture material, the patient's symptoms dramatically
      improved. Although this reaction is rare, retained sutures should be considered a
      possible cause of a postoperative eczematous dermatitis that does not respond to
      standard therapies.

PMID- 16432333
TI  - A novel technique for the prophylactic plating of the osteocutaneous radial
      forearm flap donor site.
AB  - The osteocutaneous radial forearm free flap (ORFFF) provides a suitable composite
      construct for reconstruction of head and neck defects. Initial acceptance of the
      ORFFF during the 1980s waned significantly as long-term outcome studies
      demonstrated a high incidence of donor-site fractures associated with harvesting
      a segment of the cortical radius. Biomechanical and clinical studies have
      demonstrated a significant improvement in the mechanical strength of ostectomized
      long bones after prophylactic plating. Our case report identifies a novel
      technique for rigid fixation using a low-contact, locking-screw plating system
      (LCP, Synthes USA). The system provides a fixed-angle construct using a locking
      screw system that provides appropriate axial load transfer using unicortical
      screw fixation.

PMID- 16432335
TI  - Malignant melanocytic trichoblastoma.
AB  - Trichoblastoma is an uncommon benign cutaneous neoplasm of the hair germ cell.
      The pigmented variety of the tumor is rare. There have only been a few case
      reports describing the malignant counterpart of trichoblastoma. There are no
      reports describing a pigmented variety of malignant trichoblastoma. We are
      presenting a case report of a 47-year-old patient with malignant trichoblastoma
      containing melanin deposits and propose to define this variety of the tumor as a
      separate entity: malignant melanocytic trichoblastoma.

PMID- 16432336
TI  - Rational treatment for multiple digit congenital absence: case report of
      nonvascularized toe phalangeal transfers and distraction lengthening for
      symbrachydactyly.
AB  - A case is discussed in which a young male was born with symbrachydactyly of
      multiple digits in whom nonvascularized proximal toe phalanges were transferred
      to the aphalangic digits when he was an infant. This initial surgical procedure
      was later followed by webspace deepening and ultimately by distraction
      lengthening of the digits. At 8 years of age, he has a very functional hand with
      mobile metacarpophalangeal joints in all reconstructed fingers. In fact, he uses
      this reconstructed right hand as his dominant extremity. The case is discussed in
      context of phalangeal growth potential, specific indications for this type of
      reconstruction, and final long-term outcome. This case also helps to recommend
      rational treatment protocols for similar congenital hand anomalies.

PMID- 16432337
TI  - Ipsilateral reversed free fibula transfer for femoral shaft reconstruction: a
      modification of a previously reported technique.

PMID- 16432338
TI  - Adam, Eve, and Tagliacozzi.

PMID- 16432339
TI  - The place of laser treatment in the management of congenital melanocytic nevi.

PMID- 16432340
TI  - A novel technique to suspend the brow.

PMID- 16432341
TI  - Microfollicular hair transplantation may be a simple solution to camouflage self
      inflicted wound scars on dorsal forearm.

PMID- 16432342
TI  - Re: Nipple reconstruction: the top hat technique.

PMID- 16432343
TI  - The balloon as an internal bolster for skin grafts.

PMID- 16432344
TI  - Silicon template for nasal tip graft.

PMID- 16432345
TI  - Laparoscopic-assisted versus open ileocolic resection for Crohn's disease: a
      randomized trial.
AB  - OBJECTIVE: The aim of the study was to compare laparoscopic-assisted and open
      ileocolic resection for primary Crohn's disease in a randomized controlled trial.
      METHODS: Sixty patients were randomized for laparoscopic-assisted or open
      surgery. Primary outcome parameter was postoperative quality of life (QoL) during
      3 months of follow-up, measured by SF-36 and GIQLI questionnaire. Secondary
      parameters were operating time, morbidity, hospital stay, postoperative morphine
      requirement, pain, and costs. RESULTS: Patient characteristics were not
      different. Conversion rate was 10% (n=3). Median operating time was longer in
      laparoscopic compared with open surgery (115 versus 90 minutes; P<0.003).
      Hospital stay was shorter in the laparoscopic group (5 versus 7 days; P=0.008).
      The number of patients with postoperative morbidity within the first 30 days
      differed between the laparoscopic and open group (10% versus 33%; P=0.028). There
      was no statistically significant difference in QoL between the groups during
      follow-up. Significant time effects were found on all scales of the SF-36
      (P<0.001) and the GIQLI score (P<0.001). QoL declined in the first week, returned
      to baseline levels after 2 weeks, and was improved 4 weeks and 3 months after
      surgery. Median overall costs during the 3 months follow-up were significantly
      different: euro6412 for laparoscopic and euro8196 for open surgery (P=0.042).
      CONCLUSIONS: Although QoL measured by SF-36 and GIQLI questionnaires was not
      different for laparoscopic-assisted compared with the open ileocolic resection,
      morbidity, hospital stay, and costs were significantly lower.

PMID- 16432348
TI  - Simplified hepatic resections with the use of a Chang's needle.
AB  - OBJECTIVE: To demonstrate the use of Chang's needle for hepatic resections.
      SUMMARY BACKGROUND DATA: Specialized instruments, fine surgical skills, and good
      control of hepatic inflow and backflow are essential for hepatic resections. This
      needle was specifically designed to simplify these requirements. METHODS: Whole
      thickness interlocking sutures of the liver can first be made along the designed
      resection line with a Chang's needle; then parenchyma transection can follow
      without inflow or backflow control. This was consecutively performed on 69
      patients with primary (41), metastatic (10), and benign (18) diseases since 1997.
      RESULTS: Blood loss during parenchyma transection was reduced in 11 right
      lobectomies (652 mL), 1 3-segmentectomy (300 mL), 14 bisegmentectomies (252 mL),
      7 segmentectomies (104 mL), 12 subsegmentectomies (19 mL), 5 wedge resections (7
      mL), 18 left lateral segmentectomies (110 mL), and 1 hepatorrhaphy (minimal).
      There was no procedure-related mortality. A mild bile leakage occurred in 1 case
      (1.5%) but healed spontaneously. CONCLUSIONS: The preliminary results demonstrate
      that this maneuver is a simple, easy, and safe method for performing hepatic
      resections.

PMID- 16432347
TI  - Evidence-based treatment of acute pancreatitis: a look at established paradigms.
AB  - BACKGROUND: The management of acute pancreatitis (AP) is still based on
      speculative and unproven paradigms in many centers. Therefore, we performed an
      evidence-based analysis to assess the best available treatment. METHODS: A
      comprehensive Medline and Cochrane Library search was performed evaluating the
      indication and timing of interventional and surgical approaches, and the value of
      aprotinin, lexipafant, gabexate mesylate, and octreotide treatment. Each study
      was ranked according to the evidence-based methodology of Sackett; whenever
      feasible, we performed new meta-analyses using the random-effects model.
      Recommendations were based on the available level of evidence (A=large
      randomized; B=small randomized; C=prospective trial). RESULTS: None of the
      evaluated medical treatments is recommended (level A). Patients with AP should
      receive early enteral nutrition (level B). While mild biliary AP is best treated
      by primary cholecystectomy (level B), patients with severe biliary AP require
      emergency endoscopic papillotomy followed by interval cholecystectomy (level A).
      Patients with necrotizing AP should receive imipenem or meropenem prophylaxis to
      decrease the risk of infected necrosis and mortality (level A). Sterile necrosis
      per se is not an indication for surgery (level C), and not all patients with
      infected necrosis require immediate surgery (level B). In general, early
      necrosectomy should be avoided (level B), and single necrosectomy with
      postoperative lavage should be preferred over "open-packing" because of fewer
      complications with comparable mortality rates (level C). CONCLUSIONS: While
      providing new insights into key aspects of AP management, this evidence-based
      analysis highlights the need for further clinical trials, particularly regarding
      the indications for antibiotic prophylaxis and surgery.

PMID- 16432349
TI  - Perioperative parenteral tranexamic acid in liver tumor resection: a prospective
      randomized trial toward a "blood transfusion"-free hepatectomy.
AB  - OBJECTIVE: To examine the feasibility of a real "blood transfusion"-free
      hepatectomy in a large group of patients with liver tumors. SUMMARY BACKGROUND
      DATA: Bleeding control and blood transfusion remains problematic in liver
      resection. A real "blood transfusion"-free hepatectomy in a large group of
      patients has rarely been reported. The impact of tranexamic acid (TA), an
      antifibrinolytic agent, on blood transfusion in liver resection is unknown.
      METHODS: A prospective double-blind randomized trial was performed on elective
      liver tumor resections. In group A, TA 500 mg was intravenously administered just
      before operation followed by 250 mg, every 6 hours, for 3 days. In group B, only
      placebo was given. The patients' background, blood transfusion rates, and early
      postoperative results in the 2 groups were compared. Factors that influenced
      blood requirement were analyzed. RESULTS: There were 108 hepatectomies in group A
      and 106 hepatectomies in group B. The patients' backgrounds, operative
      procedures, and hepatectomy extent did not significantly differ between the 2
      groups. Although the differences of the operative morbidity and postoperative
      stay were not significant, a significantly lower amount of operative blood loss,
      lower blood transfusion rate, shorter operative time, and lower hospital costs
      were found in group A patients. No patient in group A received blood transfusion.
      No hospital mortality occurred in either group. Tumor size and use of TA were
      independent factors that influenced blood transfusion. CONCLUSIONS: Perioperative
      parenteral use of TA reduced the amount of operative blood loss and the need for
      blood transfusion in elective liver tumor resection. A real "blood transfusion"
      free hepatectomy may be feasible with the assistance of parenteral TA.

PMID- 16432350
TI  - Three-year follow-up of a prospective randomized trial comparing laparoscopic
      versus open gastric bypass.
AB  - OBJECTIVE: To analyze long-term weight loss, changes in comorbidities and quality
      of life, and late complications after laparoscopic and open gastric bypass.
      SUMMARY BACKGROUND DATA: Early results from our prospective randomized trial
      comparing the outcome of laparoscopic versus open gastric bypass demonstrated
      less postoperative pain, shorter length of hospital stay, fewer wound-related
      complications, and faster convalescence for patients who underwent laparoscopic
      gastric bypass. METHODS: Between May 1999 and March 2001, 155 morbidly obese
      patients were enrolled in this prospective trial, in which 79 patients were
      randomized to laparoscopic gastric bypass and 76 to open gastric bypass. Two
      patients in the laparoscopic group required conversion to open surgery; their
      data were analyzed within the laparoscopic group on an intention-to-treat basis.
      The 2 groups were well matched for body mass index, age, and gender. Outcome
      evaluation included weight loss, changes in comorbidities and quality of life,
      and late complications. RESULTS: The mean follow-up was 39+/-8 months. There were
      no significant differences in the percent of excess body weight loss between the
      2 groups at the 3-year follow-up (77% for laparoscopic versus 67% for open). The
      rate of improvement or resolution of comorbidities was similar between groups.
      Improvement in quality of life, measured by the Moorehead-Ardelt Quality of Life
      Questionnaire, was observed in both groups without significant differences
      between groups. Late complications were similar between groups except for the
      rate of incisional hernia, which was significantly greater after open gastric
      bypass (39% versus 5%, P<0.01), and the rate of cholecystectomy, which was
      greater after laparoscopic gastric bypass (28% versus 5%, P=0.03). CONCLUSIONS:
      In this randomized trial with a 3-year follow-up, we found that laparoscopic
      gastric bypass was equally effective as open gastric bypass with respect to
      weight loss and improvement in comorbidities and quality of life. A major
      advantage at long-term follow-up for patients who underwent laparoscopic gastric
      bypass was the reduction in the rate of incisional hernia.

PMID- 16432351
TI  - Clinical outcomes with laparoscopic stage M1, unresected gastric adenocarcinoma.
AB  - OBJECTIVE: For patients with laparoscopic stage M1 gastric adenocarcinoma, no
      resection of the primary tumor, and systemic chemotherapy, this study
      investigated the incidence of subsequent palliative intervention and survival.
      SUMMARY BACKGROUND DATA: Laparoscopy was performed for patients with computed
      tomography scan stage M0 disease and no significant obstruction or bleeding.
      METHODS: A prospectively maintained database for 1993 to 2002 was used to
      identify 165 patients (median age, 63 years) with laparoscopic M1 disease in the
      peritoneum (P1, adjacent to stomach, 9%; P2, few distant sites, 35%; or P3,
      disseminated, 30%) or liver (10%) or both (16%). Functional performance status
      (FPS, Eastern Cooperative Oncology Group) was 0 to 1 (84%) or 2 (16%). RESULTS:
      Subsequent intervention was performed on 50% of patients, at median interval of 4
      months (range, 1-35 months) after laparoscopy. Intervention was performed on the
      stomach for obstruction (33%), bleeding (8%), or perforation (1%) or on a distant
      site for a metastasis-related complication (20%). More than one intervention
      (maximum, 4) was performed in 21%. Laparotomy was necessary in 12%; the remainder
      had endoscopic or radiologic procedures or radiation therapy only. There was one
      intervention-related death. Median survival was 10 months, with 1-year survival
      of 39%. On multivariate analysis, better FPS (0-1; odds ratio, 4; P=0.001) and
      limited peritoneal metastasis (P1 or P2; 2; P=0.01) were independently associated
      with improved survival. CONCLUSIONS: The incidence of subsequent intervention was
      50%, but few patients had laparotomy. Intervention-related mortality was minimal.
      The burden of metastatic disease and functional performance status were important
      prognostic factors.

PMID- 16432352
TI  - Very late results of esophagomyotomy for patients with achalasia: clinical,
      endoscopic, histologic, manometric, and acid reflux studies in 67 patients for a
      mean follow-up of 190 months.
AB  - INTRODUCTION: Laparoscopic esophagomyotomy is the preferred approach to patients
      with achalasia of the esophagus, However, there are very few long-term follow-up
      studies (>10 years) in these patients. OBJECTIVE: To perform a very late
      subjective and objective follow-up in a group of 67 patients submitted to
      esophagomyotomy plus a partial antireflux surgery (Dor's technique). MATERIAL AND
      METHODS: In a prospective study that lasted 30 years, 67 patients submitted to
      surgery were divided into 3 groups: group I followed for 80 to 119 months (15
      patients); group II, with follow-up of 120 to 239 months (35 patients); and group
      III, with follow-up more than 240 months (17 patients). They were submitted to
      clinical questionnaire, endoscopic evaluation, histologic analysis, radiologic
      studies, manometric determinations, and 24-hour pH studies late after surgery.
      RESULTS: Three patients developed a squamous cell esophageal carcinoma 5, 7, and
      15 years after surgery. At the late follow-up, Visick III and IV were seen in 7%,
      23%, and 35%, according to the length of follow-up of each group. Endoscopic
      examination revealed a progressive nonsignificant deterioration of esophageal
      mucosa, histologic analysis distal to squamous-columnar junction showed a
      significant decrease of fundic mucosa in patients of group III, with increase of
      intestinal metaplasia, although not significant time. Lower esophageal sphincter
      showed a significant decrease of resting pressure 1 year after surgery, which
      remained similar at the late control. There was no return to peristaltic
      activity. Acid reflux measured by 24-hour pH studies revealed a progressive
      increase, and the follow-up was longer. Nine patients developed Barrett
      esophagus: 6 of them a short-segment and 3 a long-segment Barrett esophagus.
      Final clinical results in all 67 patients demonstrated excellent or good results
      in 73% of the cases, development of epidermoid carcinoma in 4.5%, and failures in
      22.4% of the patients, mainly due to reflux esophagitis. Incomplete myotomy was
      seen in only 1 case. CONCLUSION: In patients with achalasia submitted to
      esophagomyotomy and Dor's antireflux procedure, there is a progressive clinical
      deterioration of initially good results if a very long follow-up is performed (23
      years after surgery), mainly due to an increase in pathologic acid reflux disease
      and the development of short- or long-segment Barrett esophagus.

PMID- 16432353
TI  - Risk factors for complications after esophageal cancer resection: a prospective
      population-based study in Sweden.
AB  - OBJECTIVE: To identify risk factors for complications after resection for
      esophageal or cardia cancer. SUMMARY BACKGROUND DATA: Knowledge of risk factors
      for complications after esophageal resection for cancer is sparse, and
      prospective population-based studies are lacking. METHODS: A prospective,
      nationwide, population-based study was conducted in Sweden in April 2, 2001
      through December 31, 2003. Details about tumor characteristics and stage,
      surgical procedures, and complications were collected prospectively from the
      Swedish Esophageal and Cardia Cancer register. Medical records and specific
      charts from surgical procedures, histopathology reports, and intensive care units
      were continuously scrutinized. Multivariable logistic regression analyses were
      used to estimate relative risks and their 95% confidence intervals. RESULTS:
      Among 275 patients undergoing surgical resection for esophageal or cardia cancer,
      122 (44%) had at least one predefined complication. Operation by low-volume
      surgeons (<5 operations annually) were followed by more anastomotic leakages than
      those by surgeons with higher volume (odds ratio, 7.86; 95% confidence interval,
      2.13-29.00). Hand-sewn and stapled anastomoses did not differ regarding risk of
      anastomotic leakage. Among cardia cancer patients, transthoracic approach
      resulted in more respiratory complications compared with transhiatal (abdominal
      only) approach (odds ratio, 4.78; 95% confidence interval, 1.66-13.76). Older
      age, adjuvant oncologic therapy, and higher preoperative bleeding volume
      nonsignificantly increased the risks of complications, while no influence of sex
      or tumor stage was found. CONCLUSIONS: High-volume esophageal surgeons seem to
      lower the risk of anastomotic leakage. More large-scale studies are warranted to
      establish the roles of the other potentially important risk factors suggested in
      our study.

PMID- 16432355
TI  - Serial transverse enteroplasty enhances intestinal function in a model of short
      bowel syndrome.
AB  - OBJECTIVE/SUMMARY BACKGROUND DATA: Serial transverse enteroplasty (STEP) is a new
      intestinal lengthening procedure that has been shown to clinically increase bowel
      length. This study examined the impact of the STEP procedure upon intestinal
      function in a model of short bowel syndrome. METHODS: Young pigs (n=10) had a
      reversed segment of bowel interposed to induce bowel dilatation. Five pigs
      underwent a 90% bowel resection with a STEP procedure on the remaining dilated
      bowel while 5 served as controls and had a 90% bowel resection without a STEP
      procedure. Determinations of nutritional status, absorptive capacity, and
      bacterial overgrowth were conducted 6 weeks after resection. Statistical
      comparisons were made by 2-sample t test (significance at P<0.05). RESULTS: The
      STEP procedure lengthened the bowel from 105.2+/-7.7 cm to 152.2+/-8.3 cm
      (P<0.01). The STEP animals showed improved weight retention compared with
      controls (mean, -0.5%+/-1.8% body weight versus -17.6%+/-1.5%, P<0.001).
      Intestinal carbohydrate absorption, as measured by d-Xylose absorption and fat
      absorptive capacity as measured by serum vitamin D and triglyceride levels, were
      increased in the STEP group versus controls. Serum citrulline, a marker of
      intestinal mucosal mass, was significantly elevated in the STEP pigs compared
      with controls. None of the STEP animals but 4 of 5 control animals were noted to
      have gram-negative bacterial overgrowth in the proximal bowel. CONCLUSIONS: STEP
      improves weight retention, nutritional status, intestinal absorptive capacity,
      and serum citrulline levels in a porcine short bowel model. A salutary effect
      upon bacterial overgrowth was also noted. These data support the use of this
      operation in short bowel syndrome.

PMID- 16432354
TI  - Peritoneal carcinomatosis of colorectal origin: incidence and current treatment
      strategies.
AB  - OBJECTIVE: To review the literature with regard to the incidence and prognostic
      significance of peritoneal seeding during surgery for primary colorectal cancer
      (CRC), the incidence of intraperitoneal recurrence of CRC, and the current
      treatment strategies of established PC of colorectal origin, with special focus
      on cytoreductive surgery and intraperitoneal chemotherapy (IPEC). SUMMARY
      BACKGROUND DATA: Although hematogenous dissemination forms the greatest threat to
      patients with CRC, peritoneal carcinomatosis (PC), presumably arising from
      intraperitoneal seeding of cancer cells, is a relatively frequent event in
      patients with recurrent CRC. METHODS: The PubMed and Medline literature databases
      were searched for pertinent publications regarding the incidence and prognostic
      significance of exfoliated tumor cells in the peritoneal cavity during curative
      surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and
      the therapeutic results of systemic chemotherapy or cytoreductive surgery
      followed by IPEC. RESULTS: The incidence of peritoneal seeding during potentially
      curative surgery for primary CRC, as reported in 12 patient series, varied
      widely, from 3% to 28%, which may be explained by differences in methods to
      detect tumor cells. PC is encountered in approximately 7% of patients at primary
      surgery, in approximately 4% to 19% of patients during follow-up after curative
      surgery, in up to 44% of patients with recurrent CRC who require relaparotomy,
      and in 40% to 80% of patients who succumb to CRC. The reported median survival
      after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6
      months. Median survival after aggressive cytoreductive surgery followed by
      (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends
      to be better and varies from 12 to 32 months at the cost of morbidity and
      mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized
      controlled trial has been published confirming the superiority of aggressive
      surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative
      treatment. CONCLUSIONS: Peritoneal seeding of cancer cells possibly leading to PC
      is a rather common phenomenon in patients with CRC. Cytoreductive surgery and
      adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected
      patients and should therefore be considered in patients with resectable PC of
      colorectal origin.

PMID- 16432356
TI  - Early and late recurrence after liver resection for hepatocellular carcinoma:
      prognostic and therapeutic implications.
AB  - OBJECTIVE: To evaluate the predictive factors, the therapy, and the prognosis of
      intrahepatic recurrence (IR) after surgery for hepatocellular carcinoma (HCC).
      SUMMARY BACKGROUND DATA: The predictive factors of IR are debated. To class the
      recurrence according to the modality of presentation may help to find a
      correlation and to select the right therapy for the recurrence. METHODS: A total
      of 213 patients were evaluated. Risk factors for recurrence were related to time
      (<2 years and >2 years) and type of presentation (marginal, nodular, and
      diffuse). Prognosis and therapy for the recurrence were studied in each group of
      patients. RESULTS: IR was observed in 143 patients; 109 were early (group 1) and
      34 late recurrences (group 2). Cirrhosis, chronic active hepatitis (CAH) and HCV
      positivity were independently related to the risk of recurrence with a cumulative
      effect (92.5% of recurrences in patients with 3 prognostic factors). For group 1,
      the neoplastic vascular infiltration together with cirrhosis, HCV positivity,
      CAH, and transaminases were significant; all the 11 patients with 5 negative
      prognostic factors showed an early recurrence. On the contrary, only cirrhosis
      was related to a late recurrence. Survival rate was significantly better in late
      than in early recurrence (61.9%, 27.1% and 25.7%, 4.5% at 3-5 years); a curative
      procedure was performed in 67.6% in group 1 and 29.3% in group 2. After a radical
      treatment of IR, the survival was comparable with the group of patients without
      recurrence. CONCLUSIONS: Early and late recurrences are linked to different
      predictive factors. The modality of presentation of the recurrence together with
      the feasibility of a radical treatment are the best determinants for the
      prognosis.

PMID- 16432357
TI  - Potential value of contrast-enhanced intraoperative ultrasonography during
      partial hepatectomy for metastases: an essential investigation before resection?
AB  - OBJECTIVE: The aim of the study was to assess the clinical value of contrast
      enhanced intraoperative ultrasound (CE-IOUS) as a novel tool in the hepatic
      staging of patients undergoing liver resection. METHODS: Sixty patients scheduled
      to undergo liver resection for metastatic disease were studied. Preoperative
      staging with contrast-enhanced CT and/or MR scans was performed within 2 to 6
      weeks of operation. Following exploration, intraoperative ultrasound (IOUS) was
      performed using an HDI-5000 scanner (Philips) and a finger-probe with pulse
      inversion harmonic (PIH) capability. CE-IOUS in the PIH mode was performed in a
      standardized protocol (low MI: 0.02-0.04) after intravenous injection of 3-4 mL
      of SonoVue (Bracco spa, Milan); all detected lesions on precontrast and
      postcontrast scans were counted and mapped. Any alteration in surgical management
      was documented following CE-IOUS compared with IOUS. RESULTS: Three patients were
      excluded due to disseminated disease on exploration. CE-IOUS was significantly
      more sensitive than CT/MR and IOUS in detecting liver metastases (96.1% versus
      76.7% and 81.5%, respectively) (P<0.05); it altered surgical management in 29.8%
      (17 of 57) of cases, due to 1) additional metastases in 19.3% (11 of 57), 2) less
      metastases in 3.5% (2 of 57), 3) benign lesions wrongly diagnosed as metastasis
      on IOUS/CT in 5.3% (3 of 57), and 4) vascular proximity in 1.8% (1 of 57).
      Management was unchanged in 70.2% (40 of 57) despite additional lesions detected
      in 3.5% (2 of 57) and benign lesion wrongly diagnosed on IOUS and CT as
      metastasis in 1.8% (1 of 57). CE-IOUS altered combined IOUS/CT/MR staging in
      35.1%. CONCLUSION: These preliminary results suggest CE-IOUS is an essential tool
      prior to liver resection for metastases.

PMID- 16432358
TI  - A multi-institutional analysis of the socioeconomic determinants of breast
      reconstruction: a study of the National Comprehensive Cancer Network.
AB  - OBJECTIVE: To determine the rate of postmastectomy reconstruction and investigate
      the impact of socioeconomic status on the receipt of reconstruction. SUMMARY
      BACKGROUND DATA: The National Comprehensive Cancer Network (NCCN) Outcomes
      Project is a prospective, multi-institutional database that contains data on all
      newly diagnosed breast cancer patients treated at one of the participating
      comprehensive cancer centers. METHODS: The study cohort consisted of 2174
      patients with DCIS and stage I, II, and III invasive breast cancer who underwent
      mastectomy at one of 8 NCCN centers. Rates of reconstruction were determined.
      Logistic regression analyses were used to evaluate whether socioeconomic
      characteristics are associated with breast reconstruction. RESULTS: Overall, 42%
      of patients had breast reconstruction following mastectomy. Patients with
      Medicaid and Medicare were less likely to undergo reconstruction than those with
      managed care insurance; however, there was no difference for indemnity versus
      managed care insurance. Homemakers and retired patients had fewer reconstructions
      than those employed outside the home. Patients with a high school education or
      less were less likely to have reconstruction than those with more education. Race
      and ethnicity were not significant predictors of reconstruction. CONCLUSIONS: The
      reconstruction rate in this study (42%) is markedly higher than those previously
      reported. The type of insurance, education level, and employment status of a
      patient, but not her race or ethnicity, appear to influence the use of breast
      reconstruction. Because all patients were treated at an NCCN institution, these
      socioeconomic differences cannot be explained by access to care.

PMID- 16432359
TI  - The targeting of phosphoinositide-3 kinase attenuates pulmonary metastatic tumor
      growth following laparotomy.
AB  - OBJECTIVE: We aimed to characterize a potential role for phosphatidylinositol 3
      kinase (PI3k) in leading to accelerated postoperative metastatic tumor growth.
      BACKGROUND: PI3k enhances tumor cell survival in part by phosphorylating Akt and
      reducing apoptosis. Postoperatively, apoptosis is reduced within local
      recurrences and distant metastases. This reduction is associated with the
      phenomenon of accelerated postoperative tumor growth. METHODS: Balb/c mice
      underwent a tail vein injection of 1x10 metastatic murine mammary adenocarcinoma
      4T1 cells. Animals were divided into the following treatment groups (n=10/group):
      group A, controls; group B, DMSO intraperitoneally (IP) daily from days 14 to 21;
      group C, IP LY294002 daily from days 14 to 21; group D, laparotomy only; group E,
      laparotomy followed by IP DMSO for 7 days; and group F, laparotomy followed by
      LY294002 IP for 7 days. All laparotomies were performed on day 14. Animals were
      killed at day 28. Metastatic tumor burden was assessed using the lung/body weight
      ratio and a histologic metastatic index. Mitotic counts and apoptotic indices
      were established using a combination of hematoxylin and eosin histology and TUNEL
      immunohistochemistry. A parallel survival study was performed, and PI3k activity
      was assessed using western blots for phospho-Akt. RESULTS: Laparotomy was
      associated with increased systemic tumor burden (P=0.001). Postoperatively,
      LY294002 significantly attenuated metastatic tumor growth (P<0.001). Effective
      PI3k inhibition was confirmed by demonstrating a reduced Akt phosphorylation.
      Moreover, PI3k inhibition led to reduced proliferation, increased apoptosis
      (P<0.001), and enhanced postoperative survival (P<0.001). CONCLUSIONS: Targeting
      PI3k with postoperative LY294002 significantly attenuates the acceleration in
      postoperative metastatic tumor growth seen following laparotomy.

PMID- 16432360
TI  - Accuracy of physical examination, ultrasonography, and mammography in predicting
      residual pathologic tumor size in patients treated with neoadjuvant chemotherapy.
AB  - OBJECTIVE: To assess the accuracy of physical examination, ultrasonography, and
      mammography in predicting residual size of breast tumors following neoadjuvant
      chemotherapy. BACKGROUND: Neoadjuvant chemotherapy is an accepted part of the
      management of stage II and III breast cancer. Accurate prediction of residual
      pathologic tumor size after neoadjuvant chemotherapy is critical in guiding
      surgical therapy. Although physical examination, ultrasonography, and mammography
      have all been used to predict residual tumor size, there have been conflicting
      reports about the accuracy of these methods in the neoadjuvant setting. METHODS:
      We reviewed the records of 189 patients who participated in 1 of 2 protocols
      using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by
      physical examination, ultrasonography, and/or mammography no more than 60 days
      before their surgical resection. Size correlations were performed using Spearman
      rho analysis. Clinical and pathologic measurements were also compared
      categorically using the weighted kappa statistic. RESULTS: Size estimates by
      physical examination, ultrasonography, and mammography were only moderately
      correlated with residual pathologic tumor size after neoadjuvant chemotherapy
      (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy
      of +/-1 cm in 66% of patients by physical examination, 75% by ultrasonography,
      and 70% by mammography. Kappa values (0.24-0.35) indicated poor agreement between
      clinical and pathologic measurements. CONCLUSION: Physical examination,
      ultrasonography, and mammography were only moderately useful for predicting
      residual pathologic tumor size after neoadjuvant chemotherapy.

PMID- 16432361
TI  - Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning
      tumors of the pancreas.
AB  - OBJECTIVE: To analyze the penetrance and clinical course of isolated
      nonfunctioning tumors of the pancreas (NFTP) in MEN 1 patients, and to propose a
      strategy for managing them. SUMMARY BACKGROUND DATA: Pancreaticoduodenal tumors
      develop in a majority of MEN 1 patients and are a major cause of death. The
      natural history of NFTP is poorly defined, and no clear-cut guidelines have been
      widely accepted regarding treatment. METHODS: Data on 108 patients with isolated
      NFTP among 579 MEN 1 patients from the French Endocrine Tumor Study Group (GTE)
      were analyzed. Survival rates were calculated using the Kaplan-Meier method.
      RESULTS: The penetrance of NFTP was 34% at age 50, making it the most frequent
      pancreaticoduodenal tumor in MEN 1 patients. Forty-three patients (40%) underwent
      surgery, 32 of them curatively. No patient died because of surgery. Average life
      expectancy for patients with NFTP was shorter than that for MEN 1 patients who
      did not have pancreaticoduodenal tumors. Thirteen patients died during follow-up,
      10 due to NFTP. Tumor size was correlated with the risks of metastasis and death.
      These risks were low for patients with tumors<or=20 mm. CONCLUSIONS: NFTP are
      currently the most common tumors of the pancreaticoduodenal region in patients
      with MEN 1. Prevention of tumor spread by surgery should be balanced with
      potential operative mortality and morbidity. We do not recommend routine surgery
      for NFTP<or=20 mm.

PMID- 16432362
TI  - Q RT-PCR detection of chromogranin A: a new standard in the identification of
      neuroendocrine tumor disease.
AB  - OBJECTIVE: Message and protein expression of CgA was examined to evaluate the
      sensitivity of a PCR-based approach in the detection of covert neuroendocrine
      (NE) tissue. SUMMARY BACKGROUND DATA: Immunohistochemical (IHC) measurement of
      chromogranin A (CgA) discriminates gastrointestinal (GI) carcinoids from
      epithelial tumors. IHC is, however, an insensitive technique to identify
      micrometastases or delineate subpopulations of NE cells. METHODS: CgA gene
      expression was examined by Q-RT PCR in GI carcinoids (small intestinal and
      metastases, n=17, gastric, n=5), appendiceal tumors (n=10), and adenocarcinomas
      (gastric, n=5, colorectal, n=6). CgA protein expression levels were
      quantitatively analyzed following IHC by automated quantitative analysis (AQUA)
      in 2 tissue microarrays (GI carcinoid and GI adenocarcinoma). RESULTS: CgA gene
      was overexpressed (P<0.001) in GI carcinoids compared with GI adenocarcinomas and
      normal mucosa. Elevated levels (P<0.00001) were also identified in carcinoid
      liver and lymph node (LN) metastases. CgA levels were higher (approximately 2-4
      fold) in NE appendiceal carcinoids than in adenocarcinoids, but in GI
      adenocarcinomas were identical to normal mucosa. Histologically normal lymph
      nodes expressed detectable CgA message in 30% of cases. CgA protein levels were
      highest in primary GI carcinoids and in liver metastases and significantly
      elevated (P<0.005) compared with nonmetastatic lesions. Expression in liver and
      LN metastases was significantly elevated (P<0.000001) compared with normal.
      Analysis of mRNA by Q-RT PCR was >200-fold more sensitive than by IHC.
      CONCLUSIONS: Overexpression of CgA mRNA and protein in GI carcinoids can identify
      metastatic cells; thus, PCR for CgA can be used to identify micrometastases not
      evident by light microscopy or IHC as well as define tumors of ambivalent
      morphologic phenotype. The use of this sensitive strategy to assess NETs and
      apparently normal LNs and liver may be of future utility in defining therapeutic
      strategy.

PMID- 16432363
TI  - Race and surgical mortality in the United States.
AB  - OBJECTIVE: This study describes racial differences in postoperative mortality
      following 8 cardiovascular and cancer procedures and assesses possible
      explanations for these differences. SUMMARY BACKGROUND DATA: Although racial
      disparities in the use of surgical procedures are well established, relationships
      between race and operative mortality have not been assessed systematically.
      METHODS: We used national Medicare data to identify all patients undergoing one
      of 8 cardiovascular and cancer procedures between 1994 and 1999. We used multiple
      logistic regression to assess differences in operative mortality (death within 30
      days or before discharge) between black patients and white patients, controlling
      for patient characteristics. Adding hospital indicators to these models, we then
      assessed the extent to which racial differences in operative mortality could be
      accounted for by the hospital in which patients were cared for. RESULTS: Black
      patients had higher crude mortality rates than white patients for 7 of the 8
      operations, including coronary artery bypass, aortic valve replacement, abdominal
      aortic aneurysm repair, carotid endarterectomy, radical cystectomy, pancreatic
      resection, and esophagectomy. Among these 7 procedures, odds ratios of mortality
      (black versus white) ranged from 1.23 (95% confidence interval, 1.18-1.29) for
      CABG to 1.61 (95% confidence interval, 1.28-2.03) for esophagectomy. Adjusting
      for patient characteristics had modest or no effect on odds ratios of mortality
      by race. However, there remained few clinically or statistically significant
      differences in mortality by race after we accounted for hospital. Hospitals that
      treated a large proportion of black patients had higher mortality rates for all 8
      procedures, for white as well as black patients. CONCLUSIONS: Black patients have
      higher operative mortality risks across a wide range of surgical procedures, in
      large part because of higher mortality rates at the hospitals they attend.

PMID- 16432365
TI  - Further axillary metastases associated with isolated tumor cells in sentinel
      lymph nodes of breast cancer patients.

PMID- 16432369
TI  - Can journals help the improvement of meta-analyses quality in plastic surgery?

PMID- 16432367
TI  - Geometry and biomechanics of the esophagogastric junction: implications for
      antireflux surgery.

PMID- 16432371
TI  - Evidence for a genetic defect in oral tolerance induction in inflammatory bowel
      disease.
AB  - BACKGROUND: Previous studies have suggested that there may be a defect in the
      control of immune responses locally in the intestines of patients with
      inflammatory bowel disease (IBD). Recently, we documented a failure to induce
      oral tolerance to a fed soluble protein antigen, keyhole limpet hemocyanin (KLH),
      in IBD patients. Both Crohn's disease (CD) and ulcerative colitis (UC) appear to
      be multigenic disorders with evidence of familial segregation. In this study, we
      analyzed multiplex IBD families to determine whether the defect in oral tolerance
      induction is genetically regulated. METHODS: Patients and first-degree relatives
      from 6 multiplex families were fed KLH 50 mg on days 0 to 5 and 10 to 15,
      followed by subcutaneous immunizations on days 26 and 35. Blood was obtained and
      analyzed for KLH-specific T cell proliferative responses and cytokine production.
      Intestinal permeability was also assessed. RESULTS: In contrast to normal
      controls, all IBD patients, save 1 (10 patients out of 11 tested P<.0001 versus
      normal controls), failed to develop oral tolerance to KLH. Furthermore, in 3 of
      the 4 CD families, at least 1 unaffected family member (total of 5/14 unaffected
      individuals, P=.002 versus normal controls) also failed to tolerize. This is in
      sharp contrast to unaffected individuals with no family history of IBD (1/31
      tested to date). CONCLUSIONS: This failure of tolerance induction could not be
      attributed to increased intestinal permeability. In the UC families, the defect
      in tolerance segregated with disease. These data support a genetic defect in
      tolerance induction in CD.

PMID- 16432372
TI  - TH1/TH2-mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T
      lymphocytes into nude mice.
AB  - BACKGROUND: Transfer of CD4CD45RB T cells from normal donors to SCID/Rag-1, 2
      deficient mice, which lack T and B cells, leads to the development of a TH1
      mediated inflammatory bowel disease (IBD)-like syndrome characterized by
      extensive mononuclear cell infiltrates and epithelial cell hyperplasia. Because
      it is well known that B cells are also involved in a multitude of mechanistic
      pathways in human IBD, this study attempts to establish a new model of colitis in
      nude mice. METHODS: We transferred CD4CD45RB T cells into athymic nude mice,
      which lack thymus-dependent T cells but retain normal B cells, to establish and
      investigate a B cell-involving chronic colitis model. As a control, CD4CD25 T
      cells were also used. RESULTS: Mice reconstituted with CD4CD45RB but not CD4CD25
      T cells developed a wasting disease, with severe infiltrates of B cell aggregates
      as well as T cells, macrophages, and dendritic cells into the colon and elevated
      levels of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-4, IL
      5, and IL-10, by 7 weeks after T cell transfer. Furthermore, the infiltrated
      lamina propria B cells in colitic nude mice consisted predominantly of massive
      aggregated immunoglobulin (Ig) M- and scattered IgG-positive cells, but not IgA
      positive cells. In contrast, mice reconstituted with CD4CD45RB and CD4CD45RB did
      not develop wasting disease or colitis. CONCLUSIONS: Collectively, the power of
      the colitis model induced by the adoptive transfer of CD4CD45RB T cells into nude
      mice is that one can investigate the roles of TH2-type cells and B cells in a
      regulatory T cell-depleted condition.

PMID- 16432373
TI  - Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory
      bowel disease.
AB  - BACKGROUND: There is evidence that adipocytokines play an important role in
      metabolism and in inflammation. Because human metabolism dramatically changes in
      inflammatory bowel disease (IBD) and chronic inflammation is the hallmark of the
      disease, we studied serum levels of leptin, adiponectin, resistin, and ghrelin in
      patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison with
      healthy controls (HC). METHODS: Leptin, adiponectin, resistin, and active ghrelin
      serum levels were measured in 100 IBD patients (46 UC and 54 CD) and in 60
      matched HC using commercially available enzyme-linked immunosorbent assays.
      Leptin, adiponectin, resistin, and ghrelin levels were correlated with disease
      activity, type, localization, and treatment. RESULTS: Mean serum leptin levels
      were 10.6+/-2.0 ng/mL in UC patients, 12.5+/-2.6 ng/mL in CD patients, and 15.0+/
      1.8 ng/mL in HC (P=.01). Mean serum adiponectin levels were 9514.8+/-787.8 ng/mL
      in UC patients, 7651.1+/-613 ng/mL in CD patients, and 7270.6+/-559.4 ng/mL in HC
      (P=.05). Mean serum resistin levels were 21.2+/-2.2 ng/mL in UC patients, 18.7+/
      1.6 ng/mL in CD patients and 11.8+/-0.6 ng/mL in HC (P=.0002). Mean serum ghrelin
      levels were 48.2+/-4.2 pg/mL in UC patients, 49.4+/-4.6 pg/mL in CD patients and
      14.8+/-3.0 pg/mL in HC (P<.0001). Serum levels of these adipocytokines were not
      correlated with either C-reactive protein levels or the clinical indices of
      activity. No association between serum adipocytokines levels and disease
      localization in both UC and CD patients was found. Only serum ghrelin was
      significantly higher in ileal compared with colonic CD (P=.04). CONCLUSIONS:
      Serum levels of adiponectin, resistin, and active ghrelin are increased whereas
      serum levels of leptin are decreased in patients with IBD. Further studies are
      needed to elucidate the role of adipocytokines in IBD.

PMID- 16432374
TI  - Specificities of the fecal microbiota in inflammatory bowel disease.
AB  - BACKGROUND: Abnormalities have been described in the fecal microbiota of patients
      with IBD, but it is not known whether they are specific for inflammatory bowel
      disease (IBD) or to some extent common to other forms of colitis. The aim of this
      study was to compare the bacterial composition of the dominant fecal microbiota
      in patients with Crohn's disease (CD), ulcerative colitis (UC), infectious
      colitis (IC), and in healthy subjects (HS). METHODS: Fluorescent in situ
      hybridization adapted to flow cytometry was used to analyze the bacterial
      composition of fecal samples from 13 patients with active CD, 13 patients with
      active UC, 5 patients with IC, and 13 HS. We used 6 group-specific probes
      targeting 16S rRNA and spanning the main phylogenetic groups of the fecal
      microbiota. RESULTS: A significantly higher proportion of the total fecal
      bacteria were recognized by the 6 probes in HS (86.6%+/-12.7) and in IC (84.0%+/
      11.7) than in patients with IBD (70.9%+/-15 in CD and 60.1%+/-25.7 in UC). The
      Clostridium coccoides group was reduced in UC (20.0%+/-13.3 versus 42.0%+/-12.0
      in HS; P<.001), whereas the C leptum group was reduced in CD (13.1%+/-11.9 versus
      25.2%+/-14.2 in HS; P=.002). The Bacteroides group was more abundant in IC
      (36.4%+/-22.9) than in the other 3 groups (13.8%+/-11.8 in CD, 11.7%+/-11.7 in
      UC, 12.1%+/-7.0 in HS; P<.001 for all 3 comparisons). CONCLUSIONS: In IBD the
      dominant fecal microbiota comprises unusual bacterial species. Moreover, CD and
      UC fecal microbiota harbor specific discrepancies and differ from that of IC and
      healthy subjects.

PMID- 16432375
TI  - Low detoxification capacity in the ileal pouch mucosa of patients with ulcerative
      colitis.
AB  - BACKGROUND: An ileal pouch-anal anastomosis has become the most widely accepted
      procedure for surgical treatment of patients with ulcerative colitis (UC). The
      primary function of the ileum within the pouch changes from absorption to
      storage. Malignancies have been described in the pouch mucosa. The detoxifying
      glutathione S-transferase (GST) enzymes are involved in the mucosal protection
      against toxins and carcinogens. Levels of GSTs are much higher in the ileum as
      compared with the colon. The adaptation of the ileal pouch mucosa into a more
      colon-like phenotype possibly influences the activity and levels of GST. This
      study compares the detoxification capacity of GST of the afferent ileal limb
      mucosa with the ileal pouch mucosa of patients with UC. METHODS: Biopsies from
      normal-appearing mucosa from the ileal pouch and the ileal afferent limb were
      obtained from 18 patients with UC. GST isoforms were quantified by
      immunoblotting. GST activity was measured spectrophotometrically, and glutathione
      and cysteine levels were determined by high-performance liquid chromatography.
      RESULTS: The GST activity and GSTA1+A2 levels were significantly lower in the
      pouch compared with the afferent ileal limb of patients with UC, whereas the
      GSTP1 levels were higher in the pouch. No differences were observed in the levels
      of GSTM1, GSTT1, glutathione, or cysteine. CONCLUSIONS: The lower GST
      detoxification activity in the pouch mucosa of patients with UC may result in
      higher levels of toxins and carcinogens and thus partly contribute to the risk of
      developing malignancies in the pouch.

PMID- 16432376
TI  - A2a receptors mediate inhibitory effects of adenosine on colonic motility in the
      presence of experimental colitis.
AB  - BACKGROUND: Adenosine regulates immunity and inflammation, and acts also as a
      modulator of gut functions. In this study, we investigated the role of adenosine
      A2a receptors on colonic motility in a rat model of experimental colitis.
      METHODS: Colitis was induced by 2,4-dinitrobenzenesulfonic acid. The effects of
      ZM 241385 (A2a receptor antagonist) and CGS 21680 (A2a receptor agonist) were
      assayed on cholinergic contractions of colonic longitudinal muscle preparations
      evoked by transmural electrical stimulation (TES) or carbachol. A2a receptor
      expression in colonic neuromuscular layers was assessed by reverse transcription
      polymerase chain reaction. RESULTS: ZM 241385 increased TES-induced contractions
      in the absence or in the presence of colitis, the drug being more effective in
      colonic preparations from inflamed animals. The enhancing effects of ZM 241385
      were unaffected by guanethidine or alpha-chimotrypsin, whereas being prevented by
      Nomega-propyl-L-arginine (neuronal nitric oxide synthase inhibitor) or adenosine
      5'-(alpha,beta-methylene) diphosphate (ecto-5'-nucleotidase inhibitor). Upon
      exposure of colonic tissues from normal or inflamed rats to dipyridamole plus
      adenosine deaminase, to abate endogenous adenosine levels, CGS 21680 evoked
      concentration-dependent reductions of contractile responses to TES, which were
      more intense in preparations from inflamed rats, and were antagonized by ZM
      241385. Neither CGS 21680 nor ZM 241385 affected carbachol-induced contractions.
      Reverse transcription-polymerase chain reaction showed an increase in A2a
      receptor expression in colonic tissues isolated from inflamed animals.
      CONCLUSIONS: The adenosine system is involved in neuroplastic changes occurring
      in inflamed gut. A2a receptors modulate the activity of colonic excitatory
      cholinergic nerves via facilitatory control on inhibitory nitrergic pathways, and
      such a regulatory function is enhanced in the presence of bowel inflammation.

PMID- 16432377
TI  - Effects of changes in hemoglobin level on quality of life and cognitive function
      in inflammatory bowel disease patients.
AB  - BACKGROUND: Anemia commonly complicates inflammatory bowel disease (IBD). In
      patients with chronic renal failure, the treatment of anemia with iron+/
      erythropoietin improves both quality of life (QOL) and cognitive function (CF).
      The same drugs are effective in treating severe anemia in IBD, but there is no
      evidence to direct the treatment of mild anemia. Concern exists that the use of
      iron may exacerbate inflammation in patients with IBD. The present study examined
      the association between changes in hemoglobin (Hb) in a population of IBD
      patients and changes in QOL and CF independent of change in disease activity
      (DA). Subsidiary aims were to assess whether the use of iron was associated with
      worsening DA. METHODS: A cohort of 50 patients with IBD (29 Crohn's disease and
      21 ulcerative colitis) took part. Iron replacement was given to 21 patients with
      low Hb. Measures of QOL, CF, DA, and Hb were recorded at baseline and at 6
      months. RESULTS: The iron-treated group had lower Hb and higher DA scores
      compared with the non-iron-treated group at baseline. In a hierarchical
      regression model, changes in DA accounted for 13% (P=0.17) and changes in Hb
      accounted for 18% (P=0.005) of the variance in change in SF-36 and 12% (P=0.23)
      and 17% (P=0.009) in the Inflammatory Bowel Disease Questionnaire. In this pilot
      study, although no associations were identified between changes in Hb or DA and
      CF, increases in Hb improved QOL scores in IBD patients independent of changes in
      DA. We found no similar effect with CF, but again, the sample size was small. We
      found no evidence that iron therapy causes worsening of DA. CONCLUSIONS:
      Treatment of IBD-associated anemia with iron may lead to improvement in patients'
      QOL.

PMID- 16432378
TI  - Revolution and evolution: 30 years of ileoanal pouch surgery.
AB  - Ileal pouch-anal anastomosis (IPAA) has become the standard of care for the 25%
      of patients with ulcerative colitis who ultimately require colectomy. IPAA is
      favored by patients because it avoids the necessity for a long-term stoma. This
      review examines how 3 decades of experience with IPAA has molded current
      practice, highlighting 5- and 10-year follow-up of large series to determine
      durability and functional performance, in addition to causes of failure and the
      management of complications.

PMID- 16432379
TI  - As if mothers don't have enough to worry about...

PMID- 16432380
TI  - Are we moving forward in the biological treatment of Crohn's disease? Time will
      tell.

PMID- 16432381
TI  - Ferritin as a simple indicator of iron deficiency in anemic IBD patients.

PMID- 16432382
TI  - Common variable immunodeficiency masquerading as Crohn's ileocolitis.

PMID- 16432383
TI  - Development of the Stroke-unit Discharge Guideline: choice of assessment
      instruments for prediction in the subacute phase post-stroke.
AB  - The purpose of this paper is to present the design of an evidence-based dataset
      of assessment instruments for the prognostic factors of the Stroke-unit Discharge
      Guideline (SDG), a consensus based guideline for the decision of the discharge
      destination from the hospital stroke unit. In our systematic literature reviews
      and in known standard works we have looked for assessment instruments which are
      being used most frequently in stroke care, and subsequently we have searched for
      information regarding their validity and reliability. For 17 out of the 26
      prognostic factors we found known applicable assessment instruments. Clinical
      feasibility and psychometric properties of most of these instruments are
      sufficient to good. For two factors we had to construct a new instrument. A
      simple definition was sufficient for the remaining seven factors. The SDG
      contains an evidence-based dataset of prognostic factors and assessment
      instruments, and should be applied at the hospital stroke-unit, which is the
      first location to start with a uniform use of stroke assessment instruments. The
      SDG assessment instruments are part of the stroke service chain information
      system, which contains recently developed specifications for application in web
      based electronic patient records nationwide in The Netherlands.

PMID- 16432384
TI  - Perceptions of teachers and parents on the cognitive functioning of children with
      severe mental disability and children with congenital deafblindness.
AB  - This article reports Phase I results of a questionnaire study on the perceptions
      of US teachers and parents on the cognitive functioning of children with severe
      mental disability and children with congenital deafblindness, ages 4-12 years.
      Teachers were more likely than parents to report emerging skills and to provide
      examples of how the skill was being taught. Teachers and parents of children with
      severe mental disability had different perceptions about how children
      demonstrated understanding of cause-effect, object permanence, memory, incidental
      cues, reasoning and creativity. Teachers and parents of children with congenital
      deafblindness differed in their perceptions of how children demonstrate
      understanding of incidental cues and exhibit reasoning. Both teachers and parents
      expressed concern about whether choice making was meaningful. Novelty was
      reported to be a motivating factor for children with severe mental disability,
      while familiarity was cited as motivating for children with congenital
      deafblindness. Teachers and parents of all children cited consistency, routine
      and repetition as important to learning.

PMID- 16432385
TI  - Assessment of sexual functions after spinal cord injury in Indian patients.
AB  - This study assessed the interacting physical, psychological and social aspects of
      sexuality among 86 males and 14 females with spinal cord injury (SCI). Data
      collection involved the use of a 42-item study-specific questionnaire designed to
      determine different aspects of sexuality. Subjects were rated, after interview,
      on a scale according to an integrated index of sexual function (IISF). It was
      observed that patients scoring higher on this index were sexually more active and
      showed positive sexual adjustments. A higher incidence of complications of SCI,
      partner dissatisfaction, less partner co-operation, lower self-esteem and social
      taboos were factors responsible for less sexual activity in our patients. The
      present study suggests that there is a strong need for improved treatment of the
      medical complications of SCI, sexual counselling, literature, information and
      peer support in this country. We are of the opinion that the IISF can be utilized
      in rehabilitation settings to examine the interplay of the various complex
      factors in sexual rehabilitation post-SCI.

PMID- 16432386
TI  - A process for the systematic review of community-based rehabilitation evaluation
      reports: formulating evidence for policy and practice.
AB  - A methodological framework for conducting a systematic, mostly qualitative, meta
      synthesis of community-based rehabilitation (CBR) project evaluation reports is
      described. Developed in the course of an international pilot study, the framework
      proposes a systematic review process in phases which are strongly collaborative,
      methodologically rigorous and detailed. Through this suggested process, valuable
      descriptive data about CBR practice, strategies and outcomes may be synthesized.
      It is anticipated that future application of this methodology will contribute to
      an improved evidence base for CBR, which will facilitate the development of more
      appropriate policy and practice guidelines for disability service delivery in
      developing countries. The methodology will also have potential applications in
      areas beyond CBR, which are similarly "evidence poor" (lacking empirical
      research) but "data rich" (with plentiful descriptive and evaluative reports).

PMID- 16432387
TI  - Social inclusion in workplaces where people with intellectual disabilities are
      employed: implications for supported employment professionals.
AB  - This research investigated elements of workplace culture across eight New Zealand
      workplaces where people with intellectual disability were employed. Using a semi
      structured interview format, eight employers were surveyed, and variations in job
      entry procedures, orientation and training, company policies, job design, customs
      and practice, and social opportunities were examined. Factors influencing
      inclusion in the workplace culture of a total of 16 employees, eight supported
      employees and eight co-workers without disabilities, were identified and
      compared. The findings indicated that supported workers had a lower level of
      inclusion than co-workers. Several factors influencing inclusion of employees in
      the workplace culture were identified; full-time vs. part-time, level of
      employment support, limiting expectations and employer/co-worker attitudes. The
      use of a workplace culture survey by supported employment professionals has
      several benefits, including the identification of potentially inclusive
      workplaces, the facilitation of a good person and workplace environment match,
      the possibility of monitoring inclusion levels, encouragement of full work shift
      placements, and the provision of effective support on the job.

PMID- 16432388
TI  - Reliability and validity study of Silver's test for Hong Kong-Chinese with
      dementia.
AB  - There has been great concern regarding the functional and cognitive abilities of
      elderly people in performing activities of daily living. 'Silver's test' has been
      widely used to assess the abilities and mental functions of the aging population
      in Hong Kong. The purpose of this study was to establish the validity and
      reliability of a Chinese version of Silver's test (CVST) for Hong Kong-Chinese
      with dementia. A sample of 78 (21 male and 57 female) elderly subjects was
      recruited through two-stage cluster sampling. They were administered both the
      CVST and the Chinese Mini-Mental Status Examination (MMSE). Spearman rank-order
      correlation coefficient (rs) and intra-class correlation coefficient (ICC) showed
      that the CVST had a very good inter-rater reliability (rs=0.9573, P=0.000;
      ICC=0.9966) and test-retest reliability (rs=0.9693, P<0.001; ICC=0.9769). The
      internal consistency of the test was satisfactory (Cronbach's alpha=0.8396). The
      Mann-Whitney U-test showed that the CVST could discriminate the demented elderly
      subjects from the non-demented subjects, suggesting the best cut-off score to be
      34, yielding a high sensitivity of 96.4% and equally good specificity of 96.7%.
      There was also a high positive correlation (rs=0.9218, P<0.001) between the total
      scores of the CVST and the MMSE. Suggestions for the modification of Silver's
      test were also made. In conclusion, the initial reliability and validity of the
      CVST has been established for Hong Kong-Chinese with dementia. It appears to be a
      sensitive and practical cognitive assessment acceptable to this population.

PMID- 16432389
TI  - Predicting non-return to work in patients attending cardiac rehabilitation.
AB  - Return to work (RTW) is the primary goal in the rehabilitation of patients
      suffering from coronary heart diseases. However, in spite of expensive
      rehabilitative efforts, many patients do not resume work following cardiac
      rehabilitation. To increase cost-effectiveness, predictive tests for non-RTW are
      needed to identify patients who are at risk of applying for early retirement, for
      reasons other than medical ones, at the beginning of the rehabilitation process,
      so that the necessary intervention is incorporated into the rehabilitation
      programme. As part of a study aiming at developing an advisory programme which
      can be integrated into existing rehabilitation programmes, we developed a
      screening instrument for the identification of persons at risk of not returning
      to work at the onset of the rehabilitation process. More than 65% of the
      participants who had not returned to work 6 and 12 months following
      rehabilitation had been correctly identified as risk patients at the beginning of
      the rehabilitation process. Seventy-five percent had been correctly identified as
      not being at risk. Multiple regression analysis results showed that increased
      age, profession, positive expectations concerning RTW and level of depression
      were significant predictors of RTW. Gender and anxiety were not significant
      predictors.

PMID- 16432390
TI  - Balance training following stroke: effects of task-oriented exercises with and
      without altered sensory input.
AB  - The purpose of this study was to compare the effects of a task-oriented exercise
      program with and without altered sensory input on postural stability in subjects
      with stroke. Sixteen hemiparetic subjects, at least 6 months post-stroke, were
      randomly assigned to the experimental or control group, and participated in an 8
      week task-oriented exercise program focusing on balance and mobility exercises.
      Exercises were performed under normal conditions by the control group, and under
      conditions of vision and surface manipulation by the experimental group. Pre- and
      post-test assessments involved the measurement of the center of pressure (COP)
      displacement during double-legged stance and sit-to-stand under four sensory
      conditions: (1) eyes open, normal surface; (2) eyes open, soft surface; (3) eyes
      closed, normal surface; and (4) eyes closed, soft surface, as well as the 10-m
      walking test. Results showed significant improvements (P<0.05) in COP
      displacement under sensory conditions (1) and (2) for the experimental group
      only, and limited changes for the sit-to-stand in both groups after training.
      Significant improvements (P<0.05) were also found in both groups for the walking
      test. It is concluded that a task-oriented exercise program, assisted by sensory
      manipulation, is more effective at improving the standing balance of stroke
      subjects than a conventional task-oriented program.

PMID- 16432391
TI  - Brief osteoporosis education in an inpatient rehabilitation setting improves
      knowledge of osteoporosis in elderly patients with low-trauma fractures.
AB  - The effect of an osteoporosis education program on knowledge of osteoporosis was
      assessed in elderly rehabilitation inpatients with low-trauma fractures. A
      modified version of the Osteoporosis Questionnaire (OPQ) was administered prior
      to and following a brief education program on the rehabilitation ward, and again
      at 4-6 months. A historical control group, admitted to the same ward prior to the
      educational program, was used as a comparison. The baseline mean OPQ test score
      (out of 20) for the intervention group was 7.26. The OPQ score significantly
      increased by a mean of 2.16 during the admission. The difference was increased in
      the available subjects at the 6-month questionnaire, with a significant mean
      increase of 2.67. There was a significant correlation between admission
      Functional Independence Measure (FIM) score and both baseline OPQ score (r=0.59)
      and follow-up OPQ score (r=0.60). There was a significant correlation between
      discharge FIM score and increase in OPQ score from baseline to follow-up
      (r=0.77), and with OPQ score at follow-up (r=0.76). There was a significant
      correlation between the Mini Mental State Examination at follow-up (r=0.78), and
      the change in OPQ score between initial survey and follow-up (r=0.70).
      Osteoporosis education in elderly rehabilitation inpatients with fractures is
      effective, but requires adequate patient cognitive skills.

PMID- 16432392
TI  - Patients' expectations, motivation and multi-dimensional subjective and objective
      socio-medical success in medical rehabilitation measures.
AB  - This report describes the subjective and objective socio-medical rehabilitation
      success of a cohort of patients with a primary musculoskeletal or cardiovascular
      diagnosis 1 year after medical rehabilitation. Furthermore, the predictive value
      of patients' motivation, expectations and subjective need for rehabilitation, at
      time of application, on rehabilitation success are examined. Data were derived
      from a German study, comparing different methods of social medical assessments
      for the selection of patients for inpatient medical rehabilitation. The results
      discussed refer to a sample of 352 patients with primary orthopaedic or
      cardiovascular disease who replied to the 1-year follow-up survey. Rehabilitation
      subjectively had positive effects for the majority and a positive socio-medical
      outcome (for at least 80% of the participants); although there was lower
      subjective success concerning job-related problems and working ability. Multiple
      regression analysis showed that somatic impairments, functional disabilities in
      general life as well as health and coping-related expectations/motivation are
      significant predictors of rehabilitation success. Generally, the explained
      variance by the regression model was low and further potential criteria of
      rehabilitation success should be investigated.

PMID- 16432393
TI  - Reasons for rehospitalization in patients with spinal cord injury: 5 years'
      experience.
AB  - The aim of this study was to determine the causes of rehospitalization in
      patients with spinal cord injury (SCI) treated in Istanbul Physical Medicine and
      Rehabilitation Centre and to compare the data with previous studies. Patients who
      were rehospitalized after an initial phase of rehabilitation between 1 January
      1996 and 31 December 2001 were enrolled into the study. SCI patients aged 17
      years or over at the time of injury were included. This retrospective study was
      designed using our medical records. In 5 years, 733 SCI patients were treated and
      56 of them experienced rehospitalization. We examined the demographic and injury
      characteristics of rehospitalized patients with SCI. The SPSS computer programme
      was used for statistical analysis. We found that the rate of rehospitalization
      was 7.6%, the length of stay (LOS) was 72.21 days and the average age was 34.25
      years. The reasons for rehospitalization were, in descending order, spasticity
      25%, additional rehabilitation 21.4%, pressure sores 17.9%, urinary infection
      16.1%, spinal surgery 8.9%, urinary system surgery 5.4% and pain 5.4%.
      Statistical significance was found between mean age and causes. The patients who
      were rehospitalized because of spinal surgery had a lower mean age than those
      rehospitalized because of pain (P=0.04, F=2.4). The most frequent reasons for
      rehospitalization of patients over 25 years old were spasticity and pressure
      sores. In conclusion, SCI patients' LOS was longer than found in previous studies
      because of a lack of efficient home rehabilitation. The most frequent cause of
      rehospitalization was spasticity, because of uncontrolled medical therapy. The
      study demonstrates how education of the patients and their families is important,
      and that home-based rehabilitation services must be established and supported by
      government.

PMID- 16432394
TI  - Concerns and anticipated challenges of family caregivers following participation
      in the neuropsychological feedback of stroke patients.
AB  - Forty-five family caregivers participated in the feedback session on the
      neuropsychological test results of their close ones, victims of stroke. Following
      the feedback, the caregivers were presented with an open-ended list of concerns
      regarding the patients' level of functioning and care needs, and were asked to
      identify the concerns which they had and the challenge that they represented to
      them. A hierarchy of concerns was established based upon their frequency and the
      challenge that they represented. Results indicated that "making sure that the
      patient is safe at all times", "knowing what his/her future needs will be",
      "knowing what to do in specific situations in which the patient is unable to
      perform the task independently" and "dealing with the emotional aspects of the
      patient" are the caregivers' most prominent concerns. The hierarchy of concerns
      is discussed from the perspective of its relevance to clinical work and the need
      for clinicians to incorporate it in plans for rehabilitation.

PMID- 16432395
TI  - Serum albumin and comorbidity relative to rehabilitation outcome in geriatric
      stroke, and possible links with stroke etiology.
AB  - Factors that describe the disability status of the stroke patient on discharge
      are important when starting a rehabilitation program, both from a psychosocial
      and a financial point of view. The objective of this study was to assess how
      comorbidity and serum albumin levels relate to rehabilitation outcome in
      geriatric stroke patients. Another aim was to assess whether stroke etiology
      (ischemic or hemorrhagic) influences these links. Medical records of 80 patients
      (68 ischemic and 12 hemorrhagic strokes) older than 65 years, who had suffered
      their first stroke, were investigated. Functional performance levels at admission
      and discharge were evaluated using the Functional Independence Measure (FIM).
      Length of stay in hospital was recorded. Serum albumin levels and comorbidity
      scores on admission were noted. Correlations between these variables and
      differences between the groups categorized according to stroke etiology were
      analyzed. In the group of geriatric stroke patients as a whole, serum albumin
      level was correlated with FIM score at admission and discharge. Comorbidity score
      was negatively correlated with length of stay. In the ischemic stroke subgroup,
      serum albumin level was positively correlated with length of stay and with
      functional gain, and comorbidity score was negatively correlated with functional
      gain. Analysis of the data for the hemorrhagic stroke subgroup revealed none of
      these correlations. It was concluded that serum albumin level and comorbidity are
      useful indices in geriatric ischemic stroke patients for predicting functional
      outcome and time spent in rehabilitation.

PMID- 16432396
TI  - The waste and duplication of costly services.

PMID- 16432397
TI  - Nanosize, mega-impact, potential for medical applications of nanotechnology.

PMID- 16432401
TI  - A resorbable rivet system for pediatric craniofacial surgery: biomechanical
      testing and clinical experience.
AB  - The use of a new method of bone fixation for pediatric craniofacial surgery was
      evaluated by both biomechanical tests and clinical use. A "pull-back" rivet
      composed of 82% poly-L-lactic acid and 18% polyglycolic acid (LactoSorb) for use
      with resorbable plates was developed to obviate the traditional hand-tapping
      technique used for the placement of resorbable screws. In in vitro testing, the
      average failure load of the rivets in uniaxial pullout was nearly 50 kg and
      approximately 75 kg in shear. Approximately two thirds of their initial strength
      was retained by 6 weeks. In clinical testing, 10 patients undergoing cranial
      vault reconstruction were treated by 1.5-mm resorbable plates secured by rivets.
      Although postoperative clinical outcomes were unaffected, good engagement of the
      devices with secure plate fixation was obtained in only about 70% of the rivets
      fired. Although the novel approach of a pull-back rivet was encouraging in both
      design and in vitro testing, its clinical use is impaired by the sensitivity of
      the device to the thickness of the bone into which it is placed, as well as its
      larger diameter compared with resorbable screws.

PMID- 16432402
TI  - Surgical approaches for nasopharyngeal angiofibroma: comparative analysis and
      current trends.
AB  - This study presents a comparative analysis of current surgical approaches for the
      treatment of nasopharyngeal angiofibroma, including extension of tumors,
      postoperative morbidity, complications, and recurrence rate. Twenty-four patients
      who underwent surgery with the diagnosis of juvenile nasopharyngeal angiofibroma
      at our department between 1993 and 2003 were retrospectively reviewed according
      to their clinical presentation, surgical approaches, and prognosis. Radkowski
      staging scale was used for staging tumors. The transpalatal approach was used in
      10 patients before 1999 with tumor stages between Ia and IIa. Transpalatal
      fistula was encountered in one. Nine patients underwent transnasal endoscopic
      surgery after 1999 with tumor stages between Ia and IIIa. Lateral rhinotomy in
      four patients and a degloving approach in one patient were used with tumor stages
      between IIa and IIIa; postoperative nasal crusting was the most annoying problem
      in these groups. Recurrent tumor was seen in only one patient who had undergone
      the transpalatal approach in the 12- to 56-month follow-up period. In this
      regard, the transnasal endoscopic approach can be used successfully in place of
      the transpalatal approach due to the former's lesser surgical morbidity and wide
      lateral exposure of the field in patients with nasopharyngeal angiofibroma. Also,
      many patients who underwent lateral rhinotomy for the removal of stage IIa, IIb,
      and IIIa tumors can successfully be treated using the transnasal endoscopic
      approach. In tumors that extend, infratemporal fossa lateral rhinotomy and
      degloving approaches provide the optimal exposure but have higher potential for
      morbidity than does transnasal endoscopic surgery.

PMID- 16432403
TI  - Recurrent ectopic calcification involving the maxillofacial skeleton: A potential
      harbinger of Albright's osteodystrophy.
AB  - We present a case of osteoma cutis as the initial presenting sign of Albright's
      osteodystrophy. Albright's osteodystrophy represents a challenge in both
      diagnosis and treatment because the phenotype manifests as a broad spectrum of
      biochemical and physical findings. The syndrome may be overlooked, particularly
      in the early phases when serum calcium and phosphorous levels may be normal.
      Although surgery is the treatment of osteoma cutis, recurrence is common,
      creating frustration for the patient's family and the surgeon. In the present
      case, a girl 4 months and 2 years of age presented with refractory ectopic
      calcification emanating from the maxilla and demonstrated repeated recurrence
      after surgical resection. This ectopic calcification was not adequately
      controlled until Albright's osteodystrophy was properly diagnosed and treated. A
      differential diagnosis and surgical approach to deal with recurrent ectopic
      calcification of the facial skeleton is outlined.

PMID- 16432404
TI  - Le Fort III distraction osteogenesis in syndromal craniosynostosis.
AB  - Midface distraction osteogenesis has become a valuable technique. Although
      outcome data are available from several craniofacial centers, information
      regarding perioperative and immediate postoperative course is scarce. This report
      describes seven children, aged 4 to 17 years, with syndromal craniosynostosis in
      need of midface advancements. Most were rather complex cases with several
      previous craniofacial surgeries (mean 4.4 times, range 1-8). The Modular Internal
      Distraction System (Howmedica Leibinger, Inc., Rutherford, NJ) was used for the
      gradual Le Fort III advancements. The average midface advancement obtained was 23
      mm (range 15-30 mm), resulting in improved facial profile, normalized or improved
      dental occlusion, reduced exophthalmos, and cessation or a significant decrease
      in preoperative respiratory problems. The mean length of operation was 354
      minutes (range 300-535 minutes), and the mean amount of perioperative blood
      transfusion needed was 1251 mL (range 450-1800 mL) or 46.0 mL/kg (range 8.2-121.4
      mL/kg). Complications included subcutaneous infections inferolaterally to the eye
      (N = 3) and forehead (N = 1). One patient had worsening of her facial profile and
      underwent a subsequent fronto-orbital advancement. One patient developed a
      deviation of the nasal septum and needed a corrective rhinoplasty. One patient
      developed marked trismus and one needed reoperation and trimming of the anchoring
      titanium plate on the malar process. In one patient, the lacrimal sac was
      lacerated, leading to transient epiphora. In most patients, Le Fort III
      distraction led to a significant improvement in the facial profile. However,
      surgery is still a major undertaking, with several potential complications. In
      our hands, the rate of complications is not less than for monobloc advancement.
      Thus, the choice of operation method is not based on which method is the least
      risky but on which is best suited for the individual patient.

PMID- 16432405
TI  - Clinical experience with a new fast-resorbing polymer for bone stabilization in
      craniofacial surgery.
AB  - Polylactic acid (PLA) and polyglycolic acid have been successfully used as suture
      material during the past 30 years and have been successfully used in various
      orthopedic and craniofacial applications, with increasing frequency during the
      past 15 years. To eliminate some of the problems seen with the longer-lasting
      Macropore PLA product and other longer-lasting resorbable systems, a new fast
      resorbing polymer (FRP) was manufactured by Macropore-Medtronic Neurologic
      Technologies, Inc. from commercially available 85:15 poly(D,L-lactide-co
      glycolide) raw material using traditional melt-processing techniques. The
      delivery system is easily used and uses essentially the same instrumentation. One
      hundred and sixty eight patients who had implantation of the FRP were studied.
      Detailed clinical evaluation was completed after surgery and at each
      postoperative visit. Overall, there was a 2.1% implant-related complication rate,
      which compared favorably to the 8.5% implant-related complication rate associated
      with the longer-lasting PLA product. All patients who received FRP implants have
      had maintenance of stable bony fixation, followed by bony healing and
      satisfactory or excellent cosmetic results. The results from the FRP study
      indicate that the FRP material and implants are safe and effective in
      craniomaxillofacial applications.

PMID- 16432406
TI  - Sleep disturbances detected by a sleep apnea monitor in craniofacial surgical
      patients.
AB  - Sleep apnea in craniofacial surgery was investigated. Between January 1999 and
      December 2003, 18 patients were measured at an at least 6-month interval before
      and after surgery. Eight patients underwent palatoplasty for cleft palate, and
      the other 10 patients underwent orthognathic surgery, syndromic craniosynostosis,
      and postpharyngeal flap surgery. All patients included in the study demonstrated
      clinical signs of obstructive sleep apnea, such as snoring and cessation of
      breathing during sleep. An apnomonitor was used for presurgical and postsurgical
      sleep apnea status by measuring: 1) position during sleep; 2) percutaneous oxygen
      saturation; 3) respiratory analysis, such as the type of apnea-hypopnea,
      frequency of the events, and duration of apnea-hypopnea; 4) heart rate; and 5)
      snore analysis, such as trains, time, mean, and minimal and maximal
      amplifications. The apnea-hypopnea index (AHI) was significantly improved after
      surgery, especially in cases other than palatoplasty (7.4 +/- 8.73/h and 1.6 +/-
      0.43/h, before and after surgery, respectively; P < 0.05 excluding palatoplasty).
      The percentage of snoring to total sleep was also improved significantly (22.4 +/
      19.74% and 9.0 +/- 8.54%, before and after surgery, respectively; P < 0.01 in
      all patients). Therefore, changes in sleep apnea parameters were elucidated in
      craniofacial surgery. Palatoplasty did not necessarily worsen the sleep apnea
      status, although there were snoring and anatomic abnormalities. Detachment of the
      pharyngeal flaps improved sleep apnea, and bimaxillary advancement was effective
      in normalizing sleep apnea.

PMID- 16432407
TI  - Anatomic guides to precisely localize the zygomatic branches of the facial nerve.
AB  - Descriptions of superficial anatomic landmarks for the identification of the
      zygomatic branches of the facial nerve, and their relevance for plastic surgery,
      are lacking in the literature. This paper provides such a description and
      discusses its relevance to facial surgery. MATERIALS AND METHODS: Sixty-six
      specimens, including the parotid region, from 33 adult cadavers were dissected
      and studied. All specimens were fixed in formaldehyde, and the superficial
      tissues were removed and the zygomatic branches of the facial nerve, the parotid
      gland, the tragus and the lateral palpebral commissure were identified. The
      vertical and horizontal relationships were recorded and analyzed. RESULTS AND
      CONCLUSIONS: A total of 69.7% of the cadavers had two branches, 25.8% had three
      branches, and 4.5% had a single zygomatic branch. The mean horizontal distance of
      the zygomatic branch (the most upper one) as it emerged from the anterior border
      of the parotid gland and the tragus was 30.71 mm, whereas the mean vertical
      distance of the zygomatic branch from the midpoint between the tragus and the
      lateral palpebral commissure was 19.29 mm. The branching patterns with the buccal
      branches were reported. There were no statistical differences between the left
      and right sides or between the sexes. The zygomatic branches of the facial nerve
      were always under the oblique line between the tragus and the lateral palpebral
      commissure and have a close relationship with the buccal branches of the facial
      nerve under this anatomic landmark. Application of the results in facial surgery
      is discussed.

PMID- 16432408
TI  - Thickness of Korean upper eyelid skin at different levels.
AB  - This study aims at elucidating the thickness of the Korean upper eyelid at
      different levels. Left eyelids of 10 (9 males and 1 female) fresh Korean cadavers
      were dissected. Full thickness upper eyelids were cut and trichrome stained. The
      thickness was measured under a microscope.The thickness of upper eyelid skin
      varied at different levels. The thickest part of the upper eyelid is just below
      the eyebrow (D) (1.127 +/- 238 microm), and the thinnest skin is near the ciliary
      margin (A) (320 +/- 49 microm). The upper tarsal area (C) and mid tarsal area (B)
      are 832 +/- 213 and 703 +/- 103 microm, respectively. "A" area was significantly
      thinner than mid tarsal "B" area (P = 0.000). The skin above the tarsus was
      thicker than the "B" area, but there was no significant difference (P = 0.081).
      The skin just below the eyebrow, "D," was thicker than the upper tarsal border,
      "C" area (P = 0.011). The epidermis accounted for 11.2% of the entire skin near
      the ciliary margin. However, epidermis presented less (4.2-5.5%) of the whole
      skin at other levels (P = 0.000). The distance between ciliary margin and the
      point where the skin turns suddenly thicker was 1.89 +/- 0.23 mm. The size of the
      tarsal plate was 8.88 +/- 0.81 mm. These data of upper eyelid skin thickness may
      apply to Asian double fold surgery and also to full thickness skin donation for
      grafting.

PMID- 16432409
TI  - Anthropometric study of the upper lip and the nose of infants less than a year of
      age.
AB  - We divided healthy newborns (aged between 2 weeks and 6 months) into four groups,
      less than 2 weeks old, 60 +/- 7 days, 120 +/- 7 days, and 180 +/- 7 days, between
      June 2001 and February 2002, and each group had 40 infants. The lineal distances
      included 13 items related to the nose, mouth, and lips. The average width of the
      columella at the midpoint was 3.2, 3.5, 3.7, and 3.8 mm for the 2-week-old group,
      the 2-month-old group, the 4-month-old group, and the 6-month-old group,
      respectively. The average height of the columella was 4.7, 4.9, 5.2, and 5.3 mm.
      The average length between the medial alar bases was 13.7, 14.4, 17.4, and 17.6
      mm. The average length from the base to the tip of Cupid's bow was 9.5, 10.0,
      10.5, and 10.6 mm. The average length from the columella lateral base to the tip
      of Cupid's bow was 8.4, 9.9, 10.2, and 10.5 mm. The average length from the
      columella central base to the center of Cupid's bow was 8.3, 9.5, 9.8, and 9.9
      mm. The average width of one limb of Cupid's bow was 2.7, 3.1, 3.4, and 3.5 mm.
      The average length from the tip of Cupid's bow to the commissure was 13.4, 14.7,
      16.4, and 16.9 mm. The average intercommissural distance was 26.8, 30.3, 30.8,
      and 32.7 mm. The average width of the philtral column at the columella base was
      3.1, 3.6, 3.7, and 4.0 mm. The average width of the philtral columns at the mid
      portion was 3.7, 4.6, 4.6, and 4.6 mm. The average height of the nasal tip
      protrusion was 8.7, 11.0, 11.7, and 12.1 mm. The average width of the nose was
      20.7, 23.7, 25.3, and 25.9 mm. In conclusion, these data are expected to be
      useful for patients with a bilateral cleft lip.

PMID- 16432410
TI  - Monostotic craniofacial fibrous dysplasia: the Turkish experience.
AB  - Fibrous dysplasia is a benign developmental disorder of the bone. Ten percent of
      patients with monostotic fibrous dysplasia have craniofacial bone involvement.
      Twenty-six patients were followed up at the Neurosurgery and Otolaryngology, Head
      and Neck Surgery Departments between 1990 and 2004. The surgery was performed in
      14 patients with considerable cosmetic and functional disturbance. Twelve
      patients who had mild pain and mass at the site of the lesion were followed up.
      Cosmetic and functional results, symptom analysis, and frequency of site of
      involvement were reviewed and compared with previous series. Cranial involvement
      including frontal, parietal, sphenoidal, and occipital bones was found in 13
      (52%) patients. The next common site was the maxillary bone in 9 (33%) patients.
      Four patients had orbital decompression caused by fronto-orbital and sphenoid
      bone involvement. None of the patients had any major complication of surgery.
      Because of its benign nature and decreased growth rate after adolescence,
      surgical treatment should be reserved for those with functional impairment or
      severe cosmetic disturbance.

PMID- 16432411
TI  - Comparative study of maxillary growth and occlusal outcome after autogenous rib
      grafting in complete cleft palate defect.
AB  - Cleft palate is a congenital deformity with soft tissue and hard tissue defects.
      Normal cleft palate repairing surgery only repairs soft tissue defects, whereas
      bone defects in the hard palate still exist. Therefore, we conducted this study
      in beagles to observe the influence of bone grafting at primary surgery on
      craniofacial growth and occlusal relationships in individuals with complete cleft
      palate and to provide experimental evidence for optimal surgical procedures for
      cleft palate. Using 60 beagle puppies as subjects, we tested the effects of bone
      grafting in surgically induced palatal defect. The animals were randomly and
      equally divided into four groups: (1) unoperated controls; (2) surgically induced
      unilateral cleft palate, not repaired; (3) two-flap palatoplasty used to close
      the soft defect of the surgically induced cleft palate; (4) autogenous bone (a
      piece of rib bone) implanted into the palatal defect before two-flap palatoplasty
      was performed.Cephalometric roentgenography and plaster casts of the maxillary
      were taken preoperatively and every 4 weeks after surgery. Sixty metric cranial
      variables were measured directly from the cleaned skulls after the animals were
      killed the 34th week postoperatively. The measurement results indicated that bone
      grafting may reduce the disturbance of maxillary growth caused by the cleft
      palate and the denuded bone, but it may cause other maxillary deformities. This
      finding suggests that surgeons should be careful in choosing the method of
      primary bone grafting in repairing complete cleft palate.

PMID- 16432412
TI  - Effect of recombinant human bone morphogenetic protein-2 on mandibular
      distraction osteogenesis.
AB  - The purpose of this investigation was to study the effects of recombinant human
      bone morphogenetic protein-2 (rhBMP-2) on bone formation of mandibular
      distraction osteogenesis. Six skeletally mature sheep underwent 10 mm of
      bilateral mandibular distraction osteogenesis via a custom-made distractor. Three
      micrograms of rhBMP-2 with a collagen carrier was implanted in the osteotomy site
      of one side of the mandible during the osteotomy phase. The contralateral side
      was used as the control group, and no material was implanted into the distracted
      area. At 10 days after the end of distraction, all animals were killed, and the
      distracted calluses were harvested for radiologic and histologic analysis. New
      bone was generated in the distracted zone in all groups. Histologic and
      radiologic examination showed that the new bone formation was greater in the
      rhBMP-2 group than in the control group. Quantitative computed tomography
      evaluation, however, did not demonstrate a significantly different mean bone
      density of the regenerates between the 2 groups. The results indicate that
      application of a rhBMP-2/collagen implant during the osteotomy phase of
      distraction osteogenesis increased bone formation but did not have a significant
      effect on bone density of the regenerates.

PMID- 16432413
TI  - Assay of bone morphogenetic protein-2, -4, and -7 in human demineralized bone
      matrix.
AB  - Demineralized bone matrix (DBM) is a widely used bone graft material that derives
      its osteoinductive potential from matrix-associated bone morphogenetic proteins
      (BMPs). Prior investigations have shown that the osteoinductive potential can
      vary widely, with influence from both donor and processing sources. Although it
      is plausible that donor variance in the BMP profile can be an important
      consideration, the few published studies available have given inconsistent and
      incomplete information about this. The goal was to (1) characterize the variance
      of BMP-2, BMP-4, and BMP-7 in fully demineralized DBM derived from 20
      appropriately screened (Food and Drug Administration and the American Association
      of Tissue Banks criteria) donors (male and female, 17-65 years) and (2) using
      literature review, infer the potential for this to be an important source of
      variability in graft function. BMPs were extracted with 4 M guanidine
      hydrochloride, and levels of BMP-2, BMP-4, and BMP-7 were measured using enzyme
      linked immunosorbent assay. Measured levels were as follows: BMP-2 = 21.4 +/-
      12.0 ng/g DBM, BMP-4 = 5.45 +/- 2.04 ng/g DBM, and BMP-7 = 84.1 +/- 34.4 ng/g
      DBM, which were significantly different (P < 0.05). There was a positive linear
      correlation between BMP-2 and BMP-7 (P = 0.0227). DBM derived from female donors
      had significantly greater concentrations of BMP-2 and BMP-7 than did that derived
      from male donors (P = 0.0257 and 0.0245, respectively). There was no significant
      correlation between donor age and the levels of any of the measured BMPs. The
      magnitude of variance of BMP profile appears to reasonably well correspond to the
      variance in osteoinductive potential cited by others, suggesting the possibility
      of using this as a method of donor screening.

PMID- 16432414
TI  - Nanostructural and nanomechanical properties of synostosed postnatal human
      cranial sutures.
AB  - Craniosynostosis represents a heterogeneous cluster of congenital disorders and
      manifests as premature ossification of one or more cranial sutures. Cranial
      sutures serve to enable calvarial growth and function as joints between skull
      bones. The mechanical properties of synostosed cranial sutures are of vital
      importance to their function and yet are poorly understood. The present study was
      designed to characterize the nanostructural and nanomechanical properties of
      synostosed postnatal sagittal and metopic sutures. Synostosed postnatal sagittal
      sutures (n = 5) and metopic sutures (n = 5) were obtained from craniosynostosis
      patients (aged 9.1 +/- 2.8 months). The synostosed sutural samples were prepared
      for imaging and indentation on both the endocranial and ectocranial surfaces with
      the cantilever probe of an atomic force microscopy. Analysis of the
      nanotopographic images indicated robust variations in sutural surface
      characteristics with localized peaks and valleys. In 5 x 5 mum scan sizes, the
      surface roughness of the synostosed metopic suture was significantly greater
      (223.6 +/- 93.3 nm) than the synostosed sagittal suture (142.9 +/- 80.3 nm) (P <
      0.01). The Young's modulus of the synostosed sagittal suture at 0.7 +/- 0.2 MPa
      was significantly higher than the synostosed metopic suture at 0.5 +/- 0.1 MPa (P
      < 0.01). These data suggest that various synostosed cranial sutures may have
      different structural and mechanical characteristics.

PMID- 16432416
TI  - Effect of recombinant human bone morphogenetic protein-2 on mandibular
      distraction at different rates in an experimental model.
AB  - This study evaluates the effect of recombinant human (rh) bone morphogenetic
      protein (BMP)-2 on mandibular distraction at normal and rapid distraction rates.
      This study also determines the feasibility of compensating for the increased
      distraction rate by the addition of rhBMP-2 while maintaining the quality of the
      distraction regenerate. Twenty-four New Zealand white rabbits were divided into 2
      groups, 1 treated at a normal distraction rate (0.9 mm/d) and the other at a
      rapid distraction rate (2.7 mm/d). At the end of the active distraction period,
      rhBMP-2 was injected into distraction regenerate, and the contralateral side was
      used as a control. The distraction regenerates were analyzed by plain
      radiography, microcomputed tomography, and mechanical testing. The results showed
      that rhBMP-2 can promote bone formation at both rapid and normal distraction
      rates. At week 2 and week 4 of consolidation, bone volumes in the BMP-injection
      sides were significantly higher than in the control sides, but no statistically
      significant difference was observed between the BMP-injection sides of the rapid
      and normal distraction groups. At week 8 of consolidation, mechanical testing
      demonstrated no significant difference of the failure load and stiffness between
      the BMP-injection and control sides. In conclusion, the study indicates that
      rhBMP-2 can enhance bone ossification at both normal and rapid distraction rates.
      The addition of rhBMP-2 can compensate for the rapid distraction rate in
      mandibular distraction osteogenesis. However, in the long term, the bone quality
      and stiffness of the distraction regeneration was not influenced by rhBMP-2.

PMID- 16432418
TI  - Micro-computed tomography evaluation of the glenoid fossa and mandibular condyle
      bone after bilateral vertical ramus mandibular distraction in a canine model.
AB  - The aim of this study was to quantify bone microarchitecture within the glenoid
      fossa and mandibular condyle following mandibular distraction osteogenesis. Eight
      6- to 9-month-old male beagle dogs underwent bilateral vertical mandibular
      distraction with semiburied distractors (12 days of distraction at 1 mm per day).
      One unoperated animal served as control. After distraction the animals were
      divided into two groups (N = 4) and killed after 1 or 2 months of consolidation.
      Three-dimensional trabecular architecture was analyzed by micro-computed
      tomography (muCT). At both sites the overall trends were similar. In the glenoid
      fossa, there was decreased bone volume, trabecular number, and connectivity
      density and increased trabecular separation at 1 month and decreased trabecular
      thickness and increased structure model index compared with the control (P <
      0.05). In the mandibular condyle, there was decreased bone volume, trabecular
      number, and connectivity density at both 1 and 2 months, with decreased
      trabecular thickness and increased structure model index at 2 months only
      compared with the control (P < 0.05). The bone became less dense and more
      rodlike. These bone changes are similar to those seen by the effects of aging or
      impaired normal function. Thus, in the short term, changes occur in the bone
      microstructure of the glenoid fossa and mandibular condyle after vertical
      mandibular ramus distraction in the canine model.

PMID- 16432420
TI  - Fixation of the split calvarial graft in nasal reconstruction.
AB  - Reconstruction of nasal contour where skeletal support is deficient or absent has
      usually been achieved using autogenous bone. Membranous bone taken from the
      cranium is clearly superior to rib or iliac crest when used as autografting
      material to the craniofacial skeleton. Conventionally, the bone graft is rigidly
      fixated to the recipient nasal bone with either metal plate-screw systems or
      Kirschner wires. Reported here are the results of a single biodegradable screw
      fixation of the split calvarial graft that is used for nasal reconstruction. Ten
      patients with moderate to severe saddle nose deformity underwent reconstruction
      using the open rhinoplasty approach. The graft was harvested from the outer
      cortex of the parietal bone, shaped, and secured in place with a single
      bioresorbable screw. No significant resorption has been observed in the grafts
      and a favorable aesthetic result was achieved in all of the cases. Described
      modification in fixation of the bone graft in nasal reconstruction avoids some of
      the disadvantages of permanent materials while preserving the advantages of rigid
      fixation.

PMID- 16432419
TI  - The hydration characteristics of demineralized and nondemineralized allograft
      bone: Scientific perspectives on graft function.
AB  - Demineralized bone matrix grafts are osteoinductive due to the increase in
      bioavailability of bone morphogenetic proteins that occurs from demineralization.
      The manner by which demineralization increases their bioavailability, however, is
      not known with certainty. It is known that the mineral phase of bone masks the
      proteins of the organic matrix. Proteins depend on their interaction with water
      for their three-dimensional conformation, biologic activity, and stability. It is
      possible that demineralization allows a more complete hydration of bone matrix,
      changing the local environment and allowing the bone morphogenetic proteins to
      desorb and form a concentration gradient, signaling the appropriate cell types to
      begin the process of bone regeneration. Under similar test conditions, it was
      discovered that hydration of demineralized bone matrix powder produces a strong
      exotherm on the order of 14 degrees C whereas hydration of bone powder produces a
      smaller exotherm of about 2 degrees C. The details of the hydration reactions of
      demineralized bone matrix and bone were investigated by measuring the exotherm
      produced under varying conditions. The results suggest that bone mineral does
      mask, or limit, the ability of the organic matrix to interact with water. An
      understanding of the hydration characteristics of demineralized bone matrix can
      also help in the development of carrier systems that optimize osteoinductive
      potential.

PMID- 16432421
TI  - A pneumatic orthotic cranial molding helmet for correcting positional
      plagiocephaly.
AB  - The objective of this study was o determine the efficacy of a newly developed
      pneumatic orthotic cranial molding helmet for correcting positional
      plagiocephaly. The design was retrospective and the setting was a tertiary care
      center. Subjects were all patients in whom positional plagiocephaly has been
      diagnosed and who have been fitted by the Orthotics and Prosthetics Department
      for the helmet. Diagonal cranial lengths and widths were measured at each visit.
      Analysis included the calculation of the ratio change in oblique diameters
      compared with time, patient's age, and head circumference. Seventy-five patients
      met inclusion criteria (50 boys, 25 girls). Patients with pneumatic orthotic
      cranial molding helmet therapy had significantly improved outcomes as compared
      with pretreatment measurements (P < or = 0.0001). The helmet did not limit
      cranial growth as evidenced by significant normalization of the oblique
      measurement ratio when compared with increasing cranial circumference and age (P
      = 0.0003, P < or = 0.0001, respectively). The pneumatic orthotic cranial molding
      helmet successfully corrects positional plagiocephaly and does not hinder cranial
      growth.

PMID- 16432423
TI  - Subcranial facial bipartition osteotomy with glabellar reverse V-shaped and
      temporal approaches instead of the bicoronal approach.
AB  - Patients with Apert syndrome show hypertelorism and midfacial hypoplasia, and
      their features are significantly improved through facial bipartition surgery. In
      addition, because patients with Apert syndrome demonstrate cranial deformity as
      well as other deformities, they require multiple surgical interventions
      throughout their development. We present herein a girl with Apert syndrome for
      whom subcranial facial bipartition was performed. We could not use the coronal
      approach because she had a terribly cicatricial scalp and wide calvarial defects
      caused by previous cranial surgeries carried out at another institution.
      Therefore, we used the glabellar reverse V-shaped approach and temporal
      approaches in place of the standard approach. She enjoyed a complication-free
      intraoperative and postoperative course, and left the hospital on postoperative
      day 10. Her midfacial segment was repositioned 6 mm anteriorly and 12 mm
      inferiorly on the cephalometric measurement. Her interpupillary distance was
      altered from 83 mm preoperatively to 76 mm postoperatively. The reverse V-shaped
      glabellar approach permits more relaxation of the nasal skin and nasal
      augmentation that is more reliable, although an inconspicuous scar remains in the
      prominent area. The temporal approach is also useful, enabling easy zygomatic
      arch osteotomy and secure pterygo-maxillary separation for pterygo-maxillary
      separation through an oral approach, allowing chiseling toward the skull base.

PMID- 16432422
TI  - The model graft: reconstruction of the maxilla using a fibular bone graft
      template.
AB  - The reconstruction of the partial maxillectomy decfect with a free graft depends
      on a team approach in a coordinated manner. However, this is not always possible
      due to physical limitations or, unfortunately, pragmatic factors in the era of
      managed care. A surgical template oftentimes is the critical measure of success
      in these cases, but may not be available or easily created for the previously
      mentioned reasons. In this article, we describe the use of redundant fibular bone
      as a template for reconstruction of the partial maxillectomy defect. This is a
      satisfactory alternative to a dental template in many cases, and, we believe, in
      some cases, may even be superior because it is the graft itself. As a result
      insetting can be hastened and precious ischemic time can be lessened-all favoring
      a successful, functional result.

PMID- 16432425
TI  - The use of silicon elastomer in maxillofacial rehabilitation as a substitute for
      or in conjunction with resins.
AB  - Maxillofacial prosthetic rehabilitation aims to restore anatomic function when
      serious tissue defects are present, as a result of congenital factors, trauma, or
      surgery. The aims are both aesthetic and functional, and results are obtained
      using devices that contain, reconstruct, and fill. This study introduces a
      technique using methods and materials that are acceptable to the patient in that
      they satisfy chewing, phonetic, and aesthetic functions, while respecting bone
      structure and restoring function to the soft tissues without causing trauma to
      them. Our techniques do not use innovative materials, but ones that are
      structurally different and that, until now, have not been connected with
      attachment systems. Acrylic resin, acetylic resin, and silicon are used, each in
      such a way as to take maximum advantage of each material's characteristics and
      thus give the best results.

PMID- 16432426
TI  - Dermoid sinus and cyst of the lip.
AB  - Midline dermoid cysts, although rare, typically present as nasal or glabellar
      masses with potential sinus tract extension to the skin or to the central nervous
      system. Craniofacial dermoid cysts present in varied ways, including asymptomatic
      puncti, infection, or seizure secondary to intracranial invasion. This article
      describes the previously unreported occurrence of a midline dermoid within the
      labial frenulum diagnosed on surgical excision of the cyst and its orocutaneous
      sinus tract, which extended to the skin at the base of the columella.

PMID- 16432427
TI  - Do Craniosynostosis syndrome phenotypes with both FGFR2 and TWIST mutations have
      a worse clinical outcome?
AB  - We present three cases with both FGFR2 mutations and novel TWIST sequence
      variants. The clinical outcome in this cohort is compared with that in
      individuals with a single mutation.

PMID- 16432429
TI  - Surgical treatment of an unusual patient with Proteus syndrome.

PMID- 16432428
TI  - Hemangiopericytoma of the temporal muscle: clinical report.

PMID- 16432431
TI  - Brain abscess associated with eyelid contracture.
AB  - A 4-year-old girl presented to our hospital with inability to close her left eye
      and headache. Seven months earlier, she had fallen and her left eye had been
      injured. Physical examination and radiologic investigations revealed contracture
      of the left eye and brain abscess. The case is interesting because we have found
      out that injuries of the eyelids may lead to intracranial complications in the
      long term, although they do not cause any symptoms of an intracranial abnormality
      in the short term.

PMID- 16432430
TI  - Immediate mandibular reconstruction with microsurgical fibula flap transfer
      following wide resection for ameloblastoma.
AB  - Ameloblastoma, the most common odontogenic tumor, is a slow growing, localized
      tumor of the facial skeleton. Eighty percent of the tumors affect the mandible.
      Treatment by wide excision is curative in 95% of cases. Reconstruction by bone
      grafting has a 20% to 30% nonunion rate. We have treated three large
      ameloblastomae (>6 cm) with fibula flaps, following resection. All patients have
      healed. With follow-up times of 2 to 3 years, there has been no evidence of
      recurrence and no difficulties with postoperative evaluation for recurrent
      disease. We conclude that the fibula flap is a reliable reconstructive operation
      following resection of large ameloblastomae.

PMID- 16432432
TI  - Delayed assessment of the nasolacrimal system at naso-orbito-ethmoid fractures
      and a modified technique of dacryocystorhinostomy.
AB  - Nineteen patients between 8 and 65 years of age (mean age 32) who were treated
      for naso-orbito-ethmoid area traumas and suffering from epiphora were evaluated.
      The time after the trauma was at least 4 months. The patients were divided into
      two groups. The first group consisted of 10 (52.7%) patients who have undergone a
      surgical procedure for the fractures before. The second group has 9 (47.3%)
      members who have never been surgically treated after trauma. All of the patients
      were evaluated with dacryocystography. Obstruction was found to be in the bony
      nasolacrimal canal in 13 (68.4%) patients. The nasolacrimal canal was intact in
      six (31.6%) of the patients. Dacryocystorhinostomy (DCR) was essential for five
      (50%) of the patients in the first group and eight (88.8%) of the patients in the
      second group. No additional surgical intervention was carried out for nasal
      deformities of the patients resulting from naso-orbito-ethmoid fractures.
      Palpebral malposition was present in six (32%) patients. Relief in tear flow was
      supplied in all patients. Our aim is to compare the outcomes of a modified
      technique of DCR and incidence of nasolacrimal system injury in patients with
      naso-orbito-ethmoid fractures and epiphora on whom reduction was or was not
      carried out. In conclusion, early surgical reduction of naso-orbito-ethmoid
      fractures should be performed to prevent problems and deformities of the
      nasolacrimal system.

PMID- 16432433
TI  - Posttraumatic cerebrospinal fluid cyst of the orbit.
AB  - A 41-year-old woman had a motor vehicle accident and sustained a fracture of the
      left temporal bone with anterior and middle skull base involvement. After 10
      months, she developed persistent right-sided exophthalmus. Orbital computed
      tomography scans showed a soft tissue mass in the roof of the right orbit with an
      inferior calcified border. The surgery revealed a cerebrospinal fluid cyst with
      intracranial communication through the fistula in the posterior orbital roof.

PMID- 16432434
TI  - Unknown posttraumatic foreign body in facial region.
AB  - This study emphasizes the importance of scrupulous diagnostic first aid
      procedures to avoid the consequences of trauma due to a foreign body. Two
      patients were examined, both with facial trauma showing nonspecific symptoms.
      Through objective internal and external oral examination complete with clinical
      and radiographic examinations Three dimensional computed tomography (TC3D),
      foreign bodies unknown at the time of the trauma were identified. When the
      foreign bodies had been removed, the ache symptoms disappeared, restoring
      functionality and the patient's facial appearance. This study shows the need for
      detailed early diagnosis to achieve correct monitoring and therefore proper
      treatment for these patients.

PMID- 16432437
TI  - Diagnosis and classification of congenital craniofacial cleft deformities.
AB  - Classification and diagnosis of congenital craniofacial cleft deformities are
      helpful in discerning the severity of the deformity and providing guidance for
      surgical repair. Eighty-one cases of congenital craniofacial cleft deformity were
      analyzed using the Tessier classification. Depending on the location, status of
      the deformity, and results of examinations such as computed tomography, according
      to the range affected, the location and status of the deformity were designated
      by the STO classification, with S for skin, T for soft tissue, and O for os
      (craniofacial bone). The severity of the deformity is delineated by Arabic
      numerals. The analysis of 81 cases by the STO classification method showed that
      suborbital deformities mainly were Tessier 3 and 4 clefts (24.70%) and
      supraorbital deformities mainly were Tessier 9 and 10 clefts (38.27%). There was
      no definite regular pattern for the affected extent of tissues. STO
      classification can be a supplement to Tessier classification and can provide
      references for the surgical repair of craniofacial cleft deformity.

PMID- 16432435
TI  - Delayed degradation in a resorbable plating system.
AB  - Resorbable plating systems are used extensively for craniofacial reconstruction,
      particularly in children. The systems provide rigid fixation while potentially
      minimizing the long-term drawbacks of permanent plating systems such as plate
      "migration," bone growth restriction, and imaging artifact. However, the need for
      active plate resorption represents both the strength and weakness of these
      fixation systems. We present four patients who underwent cranial vault remodeling
      using a resorbable plating system, following which the plates were palpable and
      observable for at least 2 years postoperatively. All required surgical removal.
      On gross inspection, the plates had been replaced by an encapsulated spongy
      material containing yellow, grainy, cloudy liquid. The bone underlying the plates
      was depressed and irregular in contour when compared with the adjacent bone.
      Microscopic studies showed a giant cell foreign-body reaction with crystalline
      material present in the cell vacuoles.

PMID- 16432439
TI  - Treating the whole person.

PMID- 16432438
TI  - Pyrexia after transcranial surgery.
AB  - Pyrexia after transcranial surgery has been observed regularly in clinical
      practice but does not usually herald any subsequent pathologic process. However,
      the significance and incidence of this phenomenon remain uncertain. The aim of
      this study was to evaluate the incidence and timing of any pyrexia after
      transcranial surgery for craniosynostosis correction and correlate this with the
      clinical outcome to assess its significance. Retrospective review of sequential
      case notes collected over a 10 year period identified 136 transcranial operations
      undertaken for 122 cases of nonsyndromic craniosynostosis. The incidence of
      postoperative pyrexia of 38 degrees or more in the first 5 days was 76%, whereas
      that greater than 39 degrees was 11%. Pyrexia was noticed during the first 48
      hours and had a bimodal distribution. Only a single case in this series
      subsequently developed a clinically significant complication, that is, a minor
      wound infection of the skin, which was treated by antibiotics and dressings. The
      occurrence of pyrexia did not appear to be related either to sex or to any
      affected suture but occurred less frequently in those who were under 6 months
      old. We conclude that this pyrexia should be considered to be a part of the
      normal physiological response to craniofacial surgery.

PMID- 16432440
TI  - Prevalence of the metabolic syndrome in veterans with schizophrenia.
AB  - The metabolic syndrome has become a focus of clinical attention due to its high
      prevalence in the United States (23%) and impact on cardiovascular risk, yet
      limited data exist on the prevalence of this syndrome among U.S. veterans with
      schizophrenia. METHODS: A convenience sample of patients diagnosed with
      schizophrenia or schizoaffective disorder was obtained from inpatient units and
      outpatient clinics at Veterans Affairs medical centers in San Diego and Los
      Angeles. RESULTS: In this predominantly male (92.5%) sample of 80 veterans, with
      mean age of 49.0 years, the age-adjusted prevalence of the metabolic syndrome was
      51.2%, more than twice the age-adjusted prevalence in the general U.S.
      population. The female cohort was small (n = 6), but had a greater mean body mass
      index and higher prevalence of metabolic syndrome than the male subjects.
      CONCLUSIONS: The metabolic syndrome is highly prevalent in this sample of
      patients with schizophrenia and represents an enormous source of cardiovascular
      disease risk. Clinicians who treat patients with schizophrenia should monitor for
      the parameters that define the metabolic syndrome as part of the ongoing
      management of patients treated with antipsychotics.

PMID- 16432441
TI  - Is symptomatic improvement in clinical trials of cognitive-behavioral therapy for
      psychosis clinically significant?
AB  - Although cognitive-behavioral therapy (CBT) is becoming increasingly popular as
      an adjunctive treatment for psychosis, few studies to date have examined the
      clinical (in contrast to statistical) significance of treatment gains using
      standardized methods. The aim of the current study was to investigate the
      clinical significance of symptomatic reductions reported in trials of CBT for
      schizophrenia and related disorders using standardized group methods of analysis.
      An electronic literature search identified 12 studies that met the inclusion
      criteria of being randomized, controlled trials that compared CBT to routine care
      alone or to another comparison treatment. The analysis involved the following
      steps. First, reliable change on symptom measures was examined. Next, the
      proportion of patients in each study estimated to show clinically significant
      symptomatic reductions (i.e., two standard deviations) was calculated. When both
      post-treatment and follow-up data were considered, 42% of CBT conditions compared
      with only 25% of comparison conditions demonstrated reliable change on at least
      one psychotic symptom measure per study. Proportions of clinically significant
      symptomatic improvement in studies showing reliable change were similar between
      CBT and comparison conditions. Due to the adjunctive nature of CBT for
      schizophrenia and the limits imposed by the evaluation of group datasets, results
      of the current study are considered promising but preliminary. Future trials
      should examine clinical significance using similar standardized methods within
      studies, as well as broader functional outcome measures, to provide a clearer
      picture of the benefits derived from this type of intervention.

PMID- 16432442
TI  - A wellness class for inpatients with psychotic disorders.
AB  - OBJECTIVE: The purpose of this project was to educate inpatients with psychotic
      disorders, many of whom were taking second-generation antipsychotics, about
      lifestyle changes they can make to combat weight gain. METHOD: All inpatients on
      a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a
      30-minute, didactic presentation given by a medical student and a psychology
      student under the supervision of the primary investigator. The topics covered
      included the health benefits of maintaining an ideal body weight by selecting
      foods according to the USDA Food Pyramid, determining adequate food portions,
      choosing healthy meals outside the home, and beginning and adhering to an
      exercise program. Subjects completed a 13-item quiz concerning their knowledge of
      food and nutrition before and after the presentation to determine its efficacy in
      teaching patients the material. RESULTS: Fifty patients completed both the pre-
      and post-presentation tests. The mean percentage of correct answers on the pre
      test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was
      statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of
      improvement was 6.1%. CONCLUSIONS: This study demonstrates that psychotic
      individuals are able to benefit from educational presentations about nutrition
      and a healthy lifestyle. A statistically significant improvement in test scores
      suggests that subjects gained an understanding of basic concepts related to food
      choices and fitness.

PMID- 16432443
TI  - Orally versus intramuscularly administered antipsychotic drugs in psychiatric
      emergencies.
AB  - High utilization of emergency services by patients at increased risk for
      agitation and aggression makes the determination of effective therapy a major
      concern of psychiatric care. Agitated and aggressive behavior needs to be treated
      rapidly and effectively to minimize the risk to both patients and staff.
      Traditionally, short-acting intramuscular (IM) formulations of conventional
      antipsychotic drugs have been preferred in the emergency setting due to their
      rapid onset of action and the ability to administer them to uncooperative
      patients. IM injections, however, may not always be the preferred option.
      Recently, orally administered second generation (atypical) antipsychotics have
      been shown to be at least as effective in managing acute agitation as
      conventional antipsychotic drugs, with a superior tolerability profile. The
      current review evaluates pharmacokinetic parameters, formulation options, and
      clinical efficacy data for the treatment of acute agitation or aggressive
      behavior with antipsychotic medications. A synthesis of data from individual
      clinical trials, meta-analyses, review articles, and expert consensus
      recommendations is used to develop a working clinical algorithm for the acute
      management of aggression and agitation.

PMID- 16432444
TI  - Psychopharmacology and psychotherapy: what's the connection?

PMID- 16432445
TI  - The PDE-5 inhibitors and psychiatry.

PMID- 16432446
TI  - Forensic practice: a day in the life.

PMID- 16432447
TI  - Improved long-term outcome with long-acting risperidone treatment of chronic
      schizophrenia with prior partial response.

PMID- 16432448
TI  - Video recording in the assessment of violent incidents in psychiatric hospitals.
AB  - Research into causes and management of aggressive behavior in mental illness has
      been hampered by difficulties related to the accurate detection, description, and
      classification of aggression. Much aggressive behavior, particularly verbal
      aggression, is unreported or reported inaccurately. We describe the use of video
      surveillance to study aggression in psychiatric inpatients. The videos supplement
      or correct eyewitness accounts, accurately identifying aggressors and victims, as
      well as specific aggressive behaviors. Video has provided a tool for studying
      behavioral precursors and environmental catalysts of assaults. These observations
      have contributed to our efforts to create a typology of aggression based on
      underlying causes. Furthermore, video has played a direct role in clinical care,
      documenting or revealing medication side effects, as well as feigned or self
      induced injuries. The ethical and responsible use of video surveillance of
      psychiatric inpatients has the potential to enhance our understanding and
      treatment of aggression.

PMID- 16432449
TI  - The new arms race against melanoma.

PMID- 16432450
TI  - The polymerization of melanin: a poorly understood phenomenon with egregious
      biological implications.
AB  - Several hypotheses have explicitly implicated the role of an altered redox status
      of melanin in the aetiology of melanoma and macular degeneration. The balance
      between the intrinsic anti-oxidant and pro-oxidant properties of melanin is lost,
      resulting in an altered redox phenotype. We propose that such an alteration of
      the redox status of melanin may arise, in part, due to suboptimal conditions for
      the effective polymerization of melanin precursors. We suggest that a decrease in
      the degree of polymerization or molecular weight of the melanin polymer may cause
      an alteration of the redox status of the polymer towards a more pro-oxidant
      state. A higher propensity of smaller oligomers to complex metals, coupled with
      an upregulation of metallothionein expression, results in increased production of
      free radicals including the superoxide anion. This, in association with an
      increase in the rate of tyrosinase degradation, a decrease in the rate of
      tyrosinase activation, alterations to template protein structure or alterations
      in the kinetics of the oxidation of tyrosine via the Raper-Mason pathway, may
      result in an overcoming of the cellular anti-oxidant pool, an increased
      susceptibility to oxidative stress and alterations to the reaction kinetics of
      melanogenesis, thus setting up a cycle of increasing oxidative stress and
      proliferation leading to the leakage of melanin monomers outside the organelle,
      thereby causing cytotoxicity and necrosis.

PMID- 16432451
TI  - Sodium salicylate inhibits TNF-alpha-induced NF-kappaB activation, cell
      migration, invasion and ICAM-1 expression in human melanoma cells.
AB  - We have previously shown that tumour necrosis factor-alpha (TNF-alpha)
      upregulates human melanoma cell integrin expression, migration and invasion in
      vitro. The aim of this study was to investigate the effect of the non-steroidal
      anti-inflammatory agent sodium salicylate on TNF-alpha-induced activation of the
      transcription factor nuclear factor-kappaB (NF-kappaB) and upregulation of
      intercellular adhesion molecule-1 (ICAM-1), and TNF-alpha-stimulated cell
      migration and invasion through fibronectin. HBL human melanoma cells were pre
      incubated with sodium salicylate prior to stimulation with TNF-alpha for 24 h. NF
      kappaB activation was measured using an assay that detects changes in the
      expression of a luciferase reporter gene under the direct control of NF-kappaB
      transcriptional activity. The effect of sodium salicylate and TNF-alpha on HBL
      cell invasion over 20 h and migration over 24 h was studied using fibronectin
      invasion and 'scratch wound' migration models in vitro, as described previously.
      Sodium salicylate inhibited TNF-alpha-stimulated NF-kappaB activation in melanoma
      cells in a concentration-dependent manner, and this was achieved with pre
      incubation times as short as 15 min. TNF-alpha-stimulated ICAM-1 expression in
      HBL cells was also downregulated by sodium salicylate, although in a manner
      inversely related to the concentration of this agent. In functional assays, TNF
      alpha stimulated migration and invasion, and sodium salicylate significantly
      reduced the extent of melanoma invasion and migration in both the presence and
      absence of TNF-alpha. In conclusion, sodium salicylate effectively inhibited TNF
      alpha-induced upregulation of NF-kappaB, ICAM-1 expression, in-vitro migration
      and invasion in human melanoma cells, indicating that non-steroidal anti
      inflammatory drugs may be a useful therapeutic approach to oppose inflammation
      induced melanoma invasion and metastasis in vivo.

PMID- 16432452
TI  - Pulse-mediated chemotherapy enhances local control and survival in a spontaneous
      canine model of primary mucosal melanoma.
AB  - Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment
      options include surgery, chemotherapy, immunotherapy and radiation therapy;
      however, local recurrence and distant dissemination are still frequent. We
      treated locally aggressive spontaneous canine oral melanomas that, because of
      their advanced stage, were not treatable with conventional strategies. A cohort
      of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs
      received two sessions of local bleomycin, followed by the application of trains
      of biphasic pulses. The treatment was well tolerated and resulted in an overall
      response rate of 80% with 50% long-term control. Of interest, only one of the
      dogs died of metastatic disease, and four of the long-term survivors showed a
      vitiligo-like discoloration at the site of treatment, potentially suggesting a
      recruitment of the immune system by the therapy. Further studies are needed to
      characterize this approach and to determine its suitability for head and neck
      mucosal melanoma.

PMID- 16432453
TI  - Expression of cyclooxygenase-2 in benign naevi and during human cutaneous
      melanoma progression.
AB  - Cyclooxygenase-2 (COX-2) is an enzyme that plays an important role in the
      production of prostaglandins. Numerous studies have demonstrated increased levels
      of COX-2 in human cancers of different types. It is thought that COX-2 may be
      involved in the development and progression of malignant tumours. However, data
      on the changes in COX-2 expression during the development and progression of
      human melanoma are relatively limited. Moreover, the results reported by
      different groups disagree to a large extent. The aim of this work was to evaluate
      whether COX-2 protein might be considered a potential molecular marker of
      melanoma progression. The expression of COX-2 was determined
      immunohistochemically in formalin-fixed, paraffin-embedded specimens of 64 human
      melanocytic skin tumours (17 naevi, 36 primary cutaneous melanomas and 11 lymph
      node melanoma metastases, with six pairs of primary and metastatic lesions
      obtained from the same patients). It was found that the expression level of COX-2
      was dependent on both the stage and histopathological type of the melanoma.
      Collectively, our data indicate that changes in the expression level of COX-2 are
      correlated with the development and progression of human melanoma, and imply that
      the COX-2 protein may be considered a potential prognostic and predictive marker
      in malignant melanoma.

PMID- 16432454
TI  - Iodide benzamides for the in-vivo detection of melanoma and metastases.
AB  - The aim of this work was to synthesize, label and evaluate in vivo [I]N-(2
      diethylaminoethyl)-3-iodo-4-methoxybenzamide ([I]IMBA) as a radiotracer for B16
      F0 melanoma cells, in C57 mice bearing a subcutaneous melanoma tumour and
      experimentally induced lung metastases. The average radio-iodination yield
      achieved, after labelling and Sep-Pak purification, was 65%, with a radiochemical
      purity of > or = 96%. Biodistribution studies using [I]IMBA (2.2 GBq/micromol)
      showed high specific tumour uptake, with low non-target tissue background, due to
      a rapid renal clearance from the animal body (corporal retention was 19.7 +/-
      7.1% of the injected dose at 6 h and 4.00 +/- 2.4% of the injected dose at 24 h).
      The very high targeting efficiency of this radiopharmaceutical was also confirmed
      by images in which primary subcutaneous tumour and induced lung metastases were
      clearly visualized. In addition, a clear correlation was found between the uptake
      of radioactivity in the lungs (percentage of the injected dose per gram of
      tissue) and the number of metastases carried by them.

PMID- 16432455
TI  - Dermatoscopic differences between atypical melanocytic naevi and thin malignant
      melanomas.
AB  - Dermatoscopy is used to aid in the differential diagnosis of pigmented skin
      lesions. The aim of this study was to identify dermatoscopic differences between
      atypical melanocytic naevi and thin malignant melanomas. A set of 180 difficult
      cases (60 thin melanomas, 120 clinically atypical benign melanocytic naevi) was
      analysed. Differences in structure, distribution of pigmentation, presence or
      absence of important structures, total number of colours and asymmetry of the
      lesions were identified. The three-structure type, multifocal distribution of
      pigmentation, eccentric peripheral hyperpigmentation, multiple colours (three or
      more) and asymmetry of structures/colours in the dermatoscopic image were
      considerably more frequent in melanomas than in benign lesions (P<0.001, chi
      squared test). No single dermatoscopic criterion exists to discriminate between
      all melanocytic lesions with sufficient confidence. Some criteria are helpful in
      the differential diagnosis and management of difficult cases.

PMID- 16432456
TI  - Integration of gamma knife surgery in the management of cerebral metastases from
      melanoma.
AB  - The aim of this study was to investigate the effect of gamma knife surgery on the
      local control of cerebral metastases from melanoma and to assess survival. In 29
      patients, 105 of 178 cerebral metastases were treated with gamma knife surgery.
      Only five patients had metastases confined to the brain. Of the 96 metastases
      with magnetic resonance imaging follow-up, 61.5% regressed by more than 50% of
      the pretreatment volume, 25% regressing by more than 90% and 13.5% completely.
      The median survival from gamma knife surgery was 5.7 months (longest survival, 38
      months). In multivariate analyses, a larger number of lesions requiring treatment
      (P < 0.001), recursive partitioning analysis class (P = 0.009) and a long time
      interval from initial melanoma diagnosis to detection of cerebral metastases (P =
      0.001) influenced survival. It can be concluded that gamma knife surgery is a
      useful adjunct in the management of cerebral metastases from melanoma and has a
      significant impact on local control. Its greatest potential may be achieved in
      conjunction with systemic chemotherapy, especially in the presence of
      extracerebral metastases.

PMID- 16432457
TI  - Biochemotherapy with temozolomide, cisplatin, vinblastine, subcutaneous
      interleukin-2 and interferon-alpha in patients with metastatic melanoma.
AB  - The aim of this study was to determine the efficacy and tolerability of a
      biochemotherapy regimen, including low-dose subcutaneous interleukin-2 and
      temozolomide, in patients with metastatic melanoma. Treatment consisted of
      temozolomide (150 mg/m per day on days 1-5), cisplatin (20 mg/m per day
      intravenously on days 1-4), vinblastine (1.5 mg/m per day on days 1-4),
      interleukin-2 (4.5 MU/m per day subcutaneously on days 5-8) and interferon
      alpha2b (5 MU subcutaneously on days 5-9, 11, 13, 15, every 28 days). Thirty-six
      patients were included. Patients with poor prognostic factors were not excluded.
      Seventeen patients (47%) had been treated previously in an adjuvant setting with
      interferon-alpha. Four patients (11%) had been treated previously with
      chemotherapy and six (17%) had been treated with other biochemotherapy regimens.
      The distribution by American Joint Committee on Cancer staging was as follows:
      M1a in two patients (6%), M1b in 11 patients (31%) and M1c in 23 patients (64%).
      At inclusion, seven patients (19.4%) had cerebral metastases that had previously
      been treated with whole brain radiotherapy. For thirty-four evaluable patients,
      seven (20.5%) achieved an objective response. Overall, metastatic disease was
      substantially decreased or temporarily stabilized in 11 patients (32.4%; 95%
      confidence interval, 17.4-50.5). Responses were observed for all locations. The
      central nervous system was the initial site of relapse in two responding
      patients. The median survival was 10 months. The main toxicities noted were
      haematological (grades 3-4): neutropenia (1.8%), thrombocytopenia (1.8%) and
      anaemia (1.2%). It can be concluded that this regimen is well tolerated and has a
      modest activity despite the poor prognosis of our patient population. The low
      haematological toxicity rate obtained suggests that higher doses could be tried.

PMID- 16432458
TI  - A biochemotherapy regimen with concurrent administration of cisplatin,
      vinblastine, temozolomide (Temodal), interferon-alfa and interleukin-2 for
      metastatic melanoma: a phase II study.
AB  - Our objective was to evaluate the toxicity and antitumor efficacy of concurrent
      biochemotherapy in metastatic melanoma patients and the effectiveness of adding
      temozolomide to protect the brain from metastases. Twenty-three patients with
      advanced inoperable melanoma were hospitalized for 5-6 days for the following
      treatment: cisplatin 20 mg/m daily for 4 days, vinblastine 1.6 mg/m daily for 4
      days and oral temozolomide 250 mg/m daily for 5 days, with 18 x 10 IU/m
      intravenous interleukin-2 by continuous infusion for 4 days (the dose was cut
      daily by 50%) and 5 x 10 U/m interferon-alfa subcutaneously daily for 5 days,
      repeated at 28-day intervals for a maximum of nine courses. According to the
      standard World Health Organization response criterion, the objective response
      rate was 43.4% and the median survival was 18.6 months. All but one patient
      survived for more than 12 months, and no responding patient progressed first in
      the brain. Substituting dacarbazine by temozolomide in the MD Anderson melanoma
      section protocol appears to offer protection against dissemination of brain
      metastases, equal activity in the periphery and a possible lower incidence of
      toxicity due to the oral route.

PMID- 16432459
TI  - Cutaneous melanoma arising in a burn scar: two recent cases and a review of the
      literature.
AB  - Melanoma arising in a burn scar is extremely uncommon. We report two recent
      cases, including one patient in whom six distinct primary melanomas arose in the
      setting of an extensive truncal burn scar. Only 27 patients have been reported
      previously, and only three previous cases of multiple primary melanomas arising
      in a burn scar have been described.

PMID- 16432460
TI  - Accessibility to air travel correlates strongly with increasing melanoma
      incidence.
AB  - As the cost of air travel has decreased substantially in the USA and Europe over
      the past few decades, leisure travel to vacation destinations during the winter
      months has expanded significantly. This trend has probably increased the
      incidence of significant ultraviolet radiation exposure and sunburn in a broader
      population who could not previously afford this kind of travel. The purpose of
      this study was to analyse the correlation between increasing accessibility to air
      travel and melanoma incidence. This ecological study surveyed air travel patterns
      and melanoma incidence over the past three decades. Melanoma age-adjusted
      incidence was obtained from the United States Surveillance, Epidemiology, and End
      Results 9 Registry Database, 1975-2000, and the Cancer Registry of Norway, 1965
      2000. United States mean inflation-adjusted airfare prices for four airports
      linked to leisure destinations (Miami, Los Angeles, San Diego, Phoenix) were
      compared with melanoma incidence. Parallel analyses were performed using annual
      domestic passenger-kilometres and melanoma incidence in Norway. Declining United
      States leisure-specific airfares corresponded strongly with increasing melanoma
      incidence (r = 0.96, r = 0.92, P < 0.001). Modelling a 5-year time lag between
      airfare and melanoma diagnosis strengthened the association (r = 0.98, r = 0.96,
      P < 0.001). Longer time lags could not be modelled due to data limitations. Data
      from Norway similarly showed that increasing air passenger mileage corresponded
      strongly with increasing melanoma incidence. Although correlation does not equate
      to causality, the very strong relationship between increasing access to air
      travel and melanoma incidence suggests that changes in recreational patterns may
      be contributing significantly to the public health problem of melanoma.

PMID- 16432461
TI  - Anthropometric measures and risk of cutaneous malignant melanoma: a case-control
      study from Italy.
AB  - Several studies have investigated the effect of various anthropometric factors on
      the risk of cutaneous malignant melanoma (CMM). As the results are controversial,
      we analysed this issue in a case-control study conducted in Italy. The roles of
      several body size measures were investigated in a hospital-based case-control
      study of CMM conducted in Italy. The cases were 542 patients with CMM and the
      controls were 538 subjects admitted to the same hospitals as the cases for non
      dermatological and non-neoplastic diseases. The odds ratios for the highest
      versus the lowest quartile were 2.06 [95% confidence interval (CI), 1.39-3.05]
      for weight, 1.16 (95% CI, 0.80-1.68) for height, 1.90 (95% CI, 1.28-2.80) for the
      body mass index (BMI) and 1.87 (95% CI, 1.28-2.72) for the body surface area
      (BSA). When allowing for BMI and BSA in the same model, the odds ratios were 1.55
      (95% CI, 0.92-2.62) for BMI and 1.41 (95% CI, 0.85-2.33) for BSA. The present
      findings confirm that obesity increases the risk of CMM. BSA is also related to
      the risk of CMM. In terms of the population attributable risk, overweight and
      obesity would account for 31% of the cases of CMM in this Italian population,
      indicating the scope of prevention.

PMID- 16432462
TI  - Multiple common naevi in Israeli adolescents.
AB  - The most prominent known phenotypic risk factor for the development of melanoma
      is a large number of common melanocytic naevi. The aims of this study were to
      determine the prevalence of multiple common naevi in a group of 17-year-olds and
      to identify possible associated risk factors. The study subjects were
      approximately 40,000 female and 60,000 male 17-year-old Jewish Israelis
      presenting to army recruitment centres for compulsory military service during a 1
      year period from January 2003 to December 2003. Data were gathered on whole-body
      naevi count, years of education, place of residence and place of birth of the
      recruit, his/her parents and paternal grandparents. The count of whole-body naevi
      was carried out by military physicians. The multiple naevi phenotype was defined
      by the presence of more than 50 naevi. The prevalence of the phenotype was
      highest amongst recruits of American origin and lowest amongst those of Asian and
      African origin (P < 0.0001). The prevalence differed in different population
      centres, the highest being in the coastal cities of Haifa and Tel Aviv. This
      pattern corresponded to the geographical distribution of melanoma in Israel.
      Amongst male conscripts, the phenotype was more common in the better educated
      group (> or =12 years) than in the poorer educated conscripts (< or = 11 years)
      (P = 0.051). When adjusted for the factors studied, a significant correlation was
      found between a high multiple common naevi count and American and European origin
      and residence in coastal cities, reflecting the complex interplay between
      endogenous and exogenous factors of melanoma.

PMID- 16432464
TI  - Primary care optometry: are we all on the "same page"?

PMID- 16432463
TI  - High risk of cutaneous melanoma amongst carriers of the intercellular adhesion
      molecule-1 R241 allele.
AB  - We examined the relation between cutaneous melanoma risk and the intercellular
      adhesion molecule-1 (ICAM-1) gene single nucleotide polymorphisms G241R and
      K469E, as well as the circulating soluble form of ICAM-1 determined in plasma, in
      the population of Modena Province, northern Italy. Individuals carrying at least
      one R241 allele, versus those carrying the wild-type GG genotype, had a relative
      risk of melanoma of 4.3 (P = 0.022), whereas the K469E polymorphism was unrelated
      to disease risk. Soluble ICAM-1 levels above 10 ng/ml directly and strongly
      correlated with melanoma risk. In this population, individuals carrying the R241
      allele of the ICAM-1 gene appeared to show an enhanced susceptibility to
      cutaneous melanoma, possibly because of increased ICAM-1 expression.

PMID- 16432467
TI  - Carel Koch--the person.

PMID- 16432468
TI  - Tear breakup dynamics: a technique for quantifying tear film instability.
AB  - PURPOSE: The purpose of this study was to develop a novel, quantitative
      measurement of tear film breakup dynamics (TBUD) to study the phenomenon of tear
      breakup in dry eye and control subjects and its impact on dry eye symptoms.
      METHODS: Ten control and 10 dry eye subjects completed the Dry Eye (DEQ) and
      other questionnaires. After the instillation of sodium fluorescein, subjects kept
      the tested eye open for as long as possible, similar to a staring contest, while
      tear film breakup was videotaped (S-TBUD). The maximum blink interval (MBI) and
      tear breakup time (TBUT) were measured from digital movies by a masked observer.
      Individual frames of movies were converted to gray-scale images, maps of relative
      tear film fluorescence were generated, and the total area of tear breakup (AB) of
      the exposed cornea was quantified. RESULTS: On average, dry eye subjects
      demonstrated a higher AB and shorter TBUT and MBI, but only the AB was
      significantly different (p = 0.023). Subjects most often used the descriptors
      stinging and burning to describe their sensations during staring trials. The AB
      showed a high correlation between eyes and with some DEQ symptom measures.
      CONCLUSIONS: These methods allow objective quantification and tracking of the
      phenomenon of tear breakup. Our results suggest that tear breakup stresses the
      corneal surface, resulting in stimulation of underlying nociceptors. The tear
      film of dry eye subjects was less stable than controls. They had a larger AB
      measured from the last video frame before MBI (i.e., just before blinking) than
      did controls. This perhaps reflects adaptation to the repeated stress of tear
      instability in dry eye.

PMID- 16432469
TI  - Corneal hydration control in contact lens wearers with diabetes mellitus.
AB  - PURPOSE: The purpose of this study was to assess the acute swelling and recovery
      response to contact lens-induced corneal hypoxia in diabetic patients who wear
      contact lenses. METHODS: A thick, low water content, soft contact lens was fitted
      under a light patch to one eye of 23 diabetic patients and one eye of 23
      nondiabetic control subjects in a single-masked, controlled clinical study. After
      2.5 hours an ultrasonic pachymeter was used to measure the induced corneal edema
      and the rate at which the cornea recovered to baseline thickness. RESULTS: The
      induced corneal edema was significantly less for the diabetic patients compared
      with the nondiabetic control subjects (p = 0.004). The corneas of the diabetic
      patients were found to recover from the induced edema at a similar rate to the
      corneas of the nondiabetic control subjects (p = 0.28). CONCLUSIONS: Diabetes
      mellitus alters aspects of corneal hydration control.

PMID- 16432471
TI  - The Adolescent and Child Health Initiative to Encourage Vision Empowerment
      (ACHIEVE) study design and baseline data.
AB  - PURPOSE: The purpose of this study was to describe the baseline characteristics
      of subjects and methods for a multicenter, randomized clinical trial to compare
      the effects of contact lens wear and spectacle wear on children's self
      perception. METHODS: Eligible subjects are randomly assigned to wear glasses or
      contact lenses throughout the 3-year study. Self-perceptions are measured 1 month
      after randomization and every 6 months using the Self-Perception Profile for
      Children (SPPC). Children's satisfaction with spectacles and refractive error
      related visual quality of life are also measured using surveys developed for the
      study. Visual acuity, cycloplegic autorefraction, corneal curvature, and axial
      dimensions are measured annually. RESULTS: Five clinical sites enrolled 484
      subjects with a mean (+/- standard deviation [SD]) age of 10.4 +/- 1.1 years.
      Approximately three-fifths of the subjects are girls, 47.1% of the subjects are
      white, 21.5% are black, and 21.5% are Hispanic. The mean (+/- SD) cycloplegic
      spherical equivalent autorefraction of the right eye is -2.38 +/- 1.04 D, and the
      average (+/- SD) axial length of the right eye is 24.32 +/- 0.77 mm. The average
      (+/- SD) Global Self-Worth score on the SPPC is 3.20 +/- 0.62 on a scale from one
      (low perceived competence) to 4 (high perceived competence). The average (+/- SD)
      spectacle satisfaction is 59.1 +/- 26.6 on a scale from zero (no satisfaction) to
      100 (perfect satisfaction). The average refractive error-related quality of life
      score is 63.5 +/- 12.8 on a scale from zero (poor quality of life) to 100
      (excellent quality of life). CONCLUSIONS: Subjects enrolling in the ACHIEVE Study
      are an ethnically diverse group of young myopic children. Ocular characteristics
      of the sample are consistent with data presented in other randomized clinical
      trials evaluating treatments for myopic children. The data reported here
      represent the baseline data for a 3-year randomized clinical trial to investigate
      the effects of contact lens vs. spectacle wear on children's self-perceptions.

PMID- 16432470
TI  - Two presentations of contact lens-induced papillary conjunctivitis (CLPC) in
      hydrogel lens wear: local and general.
AB  - PURPOSE: The purpose of this study was to confirm that two distinct clinical
      presentations of contact lens-induced papillary conjunctivitis (CLPC), local and
      general, occur in hydrogel lens wear. METHODS: Retrospective analyses of 124 CLPC
      events were identified. The classification of CLPC was based on location and
      extent of papillae. CLPC was classified as local if papillae were present in one
      to two areas of the tarsal conjunctiva and general if papillae occurred in three
      or more areas. The CLPC events were compared with an asymptomatic control group
      in prospective clinical trials conducted from 1993 until 2003 at two clinical
      sites, Australia and India. Two hundred sixteen subjects from Australia and 914
      subjects from India wore either high Dk silicone hydrogel or low Dk hydrogel
      lenses on a 6-night (6N) or 30-night extended-wear (EW) schedule. The
      physiological responses of the ocular surface, including tarsal conjunctiva
      redness and roughness, number of papillae present, lens fit and performance, and
      subjective patient symptoms, were measured during each visit at each site. These
      variables listed were compared between local CLPC groups and asymptomatic
      controls and general CLPC groups and asymptomatic controls. RESULTS: Two types of
      CLPC in hydrogel lens wearers have been confirmed. Of the 124 CLPC events, there
      were 61 local and 63 general events. Local and general CLPC cases reported
      significantly greater frequency of symptoms compared with the asymptomatic
      controls, in particular itching, lens awareness, secretion, and blurred vision (p
      < 0.1). CONCLUSIONS: The classification of CLPC into two types, local and
      general, in hydrogel lens wear was confirmed based on presentations at both
      sites. This distribution of papillae between local and general CLPC may indicate
      separate etiologies involved in the pathogenesis of the condition.

PMID- 16432472
TI  - Evaluating masking in a randomized, double-masked clinical trial in children with
      myopia.
AB  - PURPOSES: The purposes of this study were to evaluate the success of masking in
      the Correction of Myopia Evaluation Trial (COMET), a study designed as a
      randomized, double-masked clinical trial comparing the effect of progressive
      addition lenses (PALs) with single-vision lenses (SVLs) in slowing myopia
      progression among children and to investigate the impact of unmasking on the
      treatment effect. METHODS: The success of masking of children and parents was
      assessed by questionnaires administered after the clinical trial results were
      reported and before families were informed of their child's lens assignment.
      Children and parents who correctly guessed their assignment with absolute or
      "pretty sure" certainty were considered as unmasked. The role of children's age,
      gender, and ethnicity in unmasking was evaluated using logistic regression. The
      impact of unmasking on the treatment effect at 3 years was investigated using
      analysis of variance. The success of masking of the study optometrists was
      assessed by data collected at the child's follow-up visits. RESULTS: Overall 93%
      (436 of 469) of the COMET children responded to the questions about lens
      assignment and certainty. Thirty-seven percent (163 of 436) of children met the
      criteria for being unmasked with similar results from the parents. The majority
      (91%) of the 163 "unmasked" children reported that their glasses were the main
      reason for lens identification. Although children 10 to 11 years at baseline
      became unmasked more often than did children 6 to 9 years (44% vs. 31%, p =
      0.01), there was no difference between boys and girls becoming unmasked (p =
      0.2). The treatment effect did not differ between the masked and unmasked
      children (p = 0.69). The study optometrists became unmasked for five children
      over the course of 3-year follow up. CONCLUSIONS: Masking was successfully
      maintained for the study optometrists and the majority (63%) of COMET children.
      Although some children were able to identify their lens assignment, the primary
      study outcome was not affected by unmasking.

PMID- 16432473
TI  - Prevalence rate of myopia in schoolchildren in rural Mongolia.
AB  - PURPOSE: The prevalence of myopia among some young Asian populations has been
      reported to be increasing to near epidemic proportions. Mongolia is an emerging
      Asian economy with limited ophthalmic resources. The purpose of this study was to
      define a level of myopia for school-aged children in rural Mongolia. METHODS: A
      total of 1057 schoolchildren, aged between 7 and 17 years, were examined in two
      remote, rural suums (districts) of Mongolia: one situated in the western aimag
      (province) of Khovd and the other in the central steppe's aimag of Zavkhan. The
      examination included retinoscopy, subjective refraction, best-corrected visual
      acuity, and direct ophthalmoscopy. RESULTS: The total prevalence of myopia (more
      than -0.5 D spherical equivalent) was 5.8% (95% confidence intervals [CIs], 4.4
      7.2%). Female students exhibited a significantly higher prevalence of myopia in
      comparison to male students: 8.3% (95% CIs, 6.0-10.6%) compared with 3.1%,
      respectively (95% CIs, 1.6-4.6%): p < 0.001). For those with myopia, the median
      level of myopia for both genders was -0.75 D spherical equivalent (SE) and ranged
      from -0.50 to -28.00 D SE in girls and from -0.50 to -6.50 D SE in boys.
      CONCLUSIONS: To the authors' knowledge, this is the first study to report a level
      of myopia for schoolchildren in Mongolia. The prevalence rate is low in
      comparison to reported studies for other Far Eastern countries.

PMID- 16432474
TI  - Computational aspects of the visual Strehl ratio.
AB  - PURPOSE: The recently defined visual Strehl ratio that is based on the optical
      transfer function (VSOTF) has a number of previously unidentified limitations in
      its calculation that need to be addressed. METHOD: The VSOTF is complex, not
      bounded between zero and one, and can be negative. It is also very sensitive to
      the presence of prisms in the wavefront aberration. Current reports using the
      visual Strehl ratio for objectively assessing visual performance use its real
      part in the analyses. This leads to a metric that differs from the visual Strehl
      ratio based on the modulation transfer function (VSMTF), even in the case of
      rotationally symmetric aberrations. RESULTS: An augmented visual Strehl ratio is
      proposed that overcomes the limitations of its predecessor. CONCLUSIONS: The
      augmented metric is more robust in the presence of a residual prism than the
      VSOTF, and it shows in a preliminary study that it could lead to better
      correlations with visual performance, especially in the presence of larger
      aberrations.

PMID- 16432475
TI  - Chlamydial infections among female adolescents screened in juvenile detention
      centers in Washington State, 1998-2002.
AB  - OBJECTIVE: The objective of this study was to assess trends in Chlamydia
      trachomatis positivity and associated risk factors among detained female
      adolescents. GOAL: The goal of this study was to determine trends in prevalence
      of chlamydia among detained female adolescents. STUDY DESIGN: We retrospectively
      reviewed risk factor data and chlamydia results collected by providers during
      1998-2002 at four large juvenile detention centers in Washington State that
      routinely screen female adolescents for C. trachomatis. RESULTS: Of 3,593 tests,
      a total of 493 (13.7%) were positive for chlamydia. High chlamydia positivity was
      sustained throughout the 5-year period (range, 12.5-15.0%) with no statistically
      significant trends in positivity. Independent risk factors for chlamydial
      infection included report of more than one sex partner in the previous 60 days
      (adjusted odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.19-2.04) and
      previous chlamydial infection within 12 months (adjusted OR = 1.87, 95% CI = 1.45
      2.40). CONCLUSIONS: Efforts are needed to promote chlamydia screening programs in
      juvenile detention centers because these sites have access to high-risk sexually
      active female adolescents.

PMID- 16432476
TI  - Men who have sex with men and human immunodeficiency virus/sexually transmitted
      disease control in China.
AB  - OBJECTIVES: To address the role of men who have sex with men (MSM) in the human
      immunodeficiency virus (HIV)/sexually transmitted disease (STD) epidemic in
      China. GOAL: To explore the prevalence of risky sexual behaviors and the existing
      prevention efforts among men who have sex with men (MSM) in China. STUDY DESIGN:
      Review of behavioral and STD/HIV prevention studies addressing MSM in China.
      RESULTS: Sexual risk behaviors including unprotected group sex, anal sex, casual
      sex, and commercial sex were prevalent among Chinese MSM. Many Chinese MSM also
      engaged in unprotected sex with both men and women. Most MSM either did not
      perceive that they were at risk of HIV/AIDS or underestimated their risk of
      infection. Surveillance and intervention research among these men are still in
      the preliminary stages. CONCLUSIONS: Chinese MSM are at risk for HIV/STD
      infection and potential transmission of HIV to the general population. In
      addition to sexual risk reduction among MSM, reduction of homosexuality- related
      stigma should be part of effective intervention efforts. Volunteers from the MSM
      community and health care workers in primary health care system may serve as
      valuable resources for HIV/STD prevention and control among MSM.

PMID- 16432477
TI  - Use of a commercial assay for detecting the 60 kDa chlamydial heat shock protein
      in a range of patient groups.

PMID- 16432478
TI  - Gonorrhea reinfection among sexually transmitted disease clinic attendees in
      Baltimore, Maryland.
AB  - OBJECTIVES: We hypothesized that an active follow-up program to assess for
      reinfection after gonorrhea treatment could be a useful disease control strategy.
      GOAL: We evaluated an active follow-up and repeat testing program for all
      Baltimore sexually transmitted disease clinic patients diagnosed with gonorrhea.
      STUDY DESIGN: From September 2003 to May 2004, all clients with a treated
      gonorrhea infection were advised to return 3 months later for repeat testing. If
      clients did not return as scheduled, field outreach was attempted. At follow-up
      visits, urine was tested for gonorrhea and consenting participants completed a
      behavioral survey. In addition, we reviewed morbidity records for any
      intercurrent gonorrhea infections reported during the project period. RESULTS: Of
      the 667 participants diagnosed with gonorrhea at baseline, 54 had a gonorrhea
      reinfection diagnosed for an incidence of 13.8 per 100 person-years. One hundred
      seventy-eight (27%) either presented for a follow-up visit or were located
      through field efforts, and of these, 5 (2.8%) had gonorrhea detected on follow-up
      urine testing. No measured factors had predictive value in identifying gonorrhea
      reinfection. CONCLUSIONS: Although reinfection rates were high, we found that
      field staff intervention to increase follow-up testing rates did not identify a
      significant amount of repeat infections compared with passive surveillance.

PMID- 16432479
TI  - Challenges in the control of gonorrhea in South America and the Caribbean:
      monitoring the development of resistance to antibiotics.
AB  - OBJECTIVE: : The objective of this study was to ascertain the antimicrobial
      susceptibility of Neisseria gonorrhoeae isolates from 6 South American and 13
      Caribbean countries participating in the Gonococcal Antimicrobial Surveillance
      Program (GASP) from 1990 to 1999. STUDY: : A GASP network of laboratories was
      launched in the Americas and the Caribbean during the 1990s. Standardized methods
      and interpretative criteria were established for the isolation of N. gonorrhoeae,
      strain identification, and determination, and quality control of antimicrobial
      susceptibility. RESULTS: : Two countries (Argentina and Uruguay) maintained
      continuous surveillance during the study period. Some countries gathered data
      periodically and several others were unable to initiate antimicrobial
      surveillance as a result of lack of resources. The percentage of penicillin
      resistant N. gonorrhoeae isolated in the region over the decade varied
      considerably (1.0-11.9% carried chromosomal resistance and 17.9-38.8% produced
      beta-lactamase) with an overall trend to declining numbers of penicillin
      resistant isolates. For tetracycline, 7.4% to 36.3% carried chromosomal
      resistance, whereas 12.0% to 27.4% carried plasmid-mediated resistance. There
      were no reports of ciprofloxacin-resistant isolates, although N. gonorrhoeae with
      decreased susceptibility to ciprofloxacin and azithromycin as well as
      spectinomycin-resistant isolates were identified in some countries.

PMID- 16432480
TI  - Herpes simplex virus type 2 (HSV-2) seroprevalence at the time of HIV-1 diagnosis
      and seroincidence after HIV-1 diagnosis in an ethnically diverse cohort of HIV-1
      infected persons.
AB  - OBJECTIVE: The objective of this study was to determine herpes simplex virus type
      2 (HSV-2) seroprevalence at HIV-1 diagnosis and seroincidence > or =1 year after
      HIV-1 diagnosis. METHODS: HSV type-specific antibodies were detected by enzyme
      immunoassay. RESULTS: The cohort comprised 850 adults diagnosed HIV-positive in
      1986-2001 and followed for a median of 3 years. HSV-2 seroprevalence was 63% (95%
      confidence interval [CI], 60-66%) and was associated with female gender,
      heterosexual risk group, black ethnicity, and older age. HSV-2 seroincidence was
      1.8 per 100 person-years (95% CI, 0.8-2.8) and was associated with other sexually
      transmitted diseases, including human papilloma virus infection (P = 0.005) and
      gonorrhea (P = 0.05). A diagnosis of genital herpes was made in 21% HSV-2
      seropositive persons and was more likely in those who tested HIV-positive before
      1997 (adjusted odds ratio, 5.11; 95% CI, 3.28-7.98; P = 0.0001). CONCLUSIONS:
      Results confirm the epidemiologic association between HIV-1 and HSV-2. HSV-2
      seroconversion was a marker of high-risk sexual behavior. The likelihood of
      developing symptoms of genital herpes declined from 1997 onward.

PMID- 16432481
TI  - Disclosure of HIV serostatus to sex partners: a new approach to measurement.
AB  - OBJECTIVE: The objective of this study was to assess measurement of full HIV
      serostatus disclosure (before sex), delayed disclosure (after sex), and no
      disclosure to both current and recent past (in the last year) sex partners. GOAL:
      The goal of this study was to propose a refined measure of HIV disclosure. STUDY
      DESIGN: This study consisted of a cross-sectional study using audio computer
      assisted survey interviews with 63 persons with HIV/AIDS who reported on 145 sex
      partnerships. RESULTS: Considering all sex partners in the past year, full
      disclosure occurred in 54%, delayed disclosure in 22%, and no disclosure occurred
      in 24%. Delayed/no disclosure among all partners in the past year was
      substantially higher than standard measures of no disclosure among current
      partners only, 46% (95% confidence interval [CI], 38-54%) versus 12% (95% CI, 5
      19%). No disclosure was more common in past partnerships than current
      partnerships (40% vs. 12%, P < 0.01). Predictors of disclosure included
      partnership characteristics of having an HIV-positive partner and being in a
      primary, heterosexual relationship. CONCLUSIONS: Standard measures may
      underestimate nondisclosure. Counseling and interventions that promote disclosure
      should include strategies for disclosure in ongoing relationships, assistance in
      notifying past partners, and a focus on partnership characteristics and dynamics.

PMID- 16432482
TI  - An observational cohort study of Chlamydia trachomatis treatment in pregnancy.
AB  - BACKGROUND AND OBJECTIVES: Currently, azithromycin is not considered a first-line
      treatment for Chlamydia trachomatis in pregnant women. We evaluated the use,
      efficacy, and safety of azithromycin compared with erythromycin and amoxicillin
      in the treatment of genital chlamydial infection during pregnancy. METHODS: This
      was a retrospective cohort study of pregnant women with genital chlamydial
      infection. Data on antibiotics prescribed, test-of-cure (TOC) results, and
      maternal and infant complications were collected from medical records. RESULTS:
      Of the 277 women in the study sample, 69% were initially prescribed azithromycin,
      9% amoxicillin, and 19% erythromycin. Eight-one percent of subjects had a TOC 7
      or more days after diagnosis and before delivery. Treatment efficacy, as defined
      by a negative TOC, was 97% (95% confidence interval [CI], 92.9-99.2) for
      azithromycin, 95% (95% CI, 76.2-99.9) for amoxicillin, and 64% (95% CI, 44.1
      81.4) for erythromycin. The efficacy of azithromycin was significantly higher
      than erythromycin (P < 0.0001). There were no significant differences in efficacy
      by age, race/ethnicity, concurrent sexually transmitted disease diagnosis,
      partner treatment, or substance use. Furthermore, there was no difference in
      complications for women or infants exposed to azithromycin compared with those
      treated with other regimens. CONCLUSION: Clinical outcome data from this study
      population of women and infants support both efficacy and safety of azithromycin
      for treatment of C. trachomatis in pregnancy.

PMID- 16432483
TI  - Drug users: a potentially important bridge population in the transmission of
      sexually transmitted diseases, including AIDS, in China.
AB  - OBJECTIVE: The objective of this study was to examine risk characteristics among
      bridge and nonbridge drug users. STUDY DESIGN: A cross-sectional study was
      conducted among drug users. Drug users who shared needles and engaged in sex with
      both high-risk partners and low-risk partners were defined as bridgers. RESULTS:
      A total of 312 drug users were recruited, among whom 49.4% (154) were bridgers.
      Among bridgers, 83.1% injected drugs and 35% shared needles in the past month.
      Eighty-seven percent (134) of bridgers had one or more commercial sex partners in
      the past year. Only 3.9% of the bridgers and 4.6% of nonbridgers consistently
      used condoms with regular sex partners. Fifty-eight percent of bridgers and 46.8%
      of nonbridgers tested positive for hepatitis C virus, whereas 15.6% of bridgers
      and 7% of nonbridgers tested positive for syphilis. CONCLUSIONS: The
      pervasiveness of bridgers among drug users and their risky sexual behavior
      underscore their role in the spread of sexually transmitted diseases.

PMID- 16432484
TI  - High prevalence of sexually transmitted diseases among men who have sex with men
      in Jiangsu Province, China.
AB  - OBJECTIVE: : The objective of this study was to investigate the prevalence of
      sexually transmitted diseases (STDs), including HIV infection, and sexual risk
      behaviors among men who have sex with men (MSM) in Jiangsu Province, China.
      DESIGN: : The authors conducted a cross-sectional study. METHODS: : From February
      to July 2003, men who attended 10 participating gay bars in five cities in
      Jiangsu Province were asked to complete a self-administered questionnaire,
      including measures of alcohol use and sexual risk behaviors. Blood samples and
      urethral swabs were taken to examine the presence of STDs, including HIV
      infection. RESULTS: : A total of 144 men were recruited in the study. Forty-six
      percent of men reported unprotected anal intercourse with their male sexual
      partners in the past 3 months. No one was found to be HIV-infected, but the
      prevalence of STDs was high: gonorrhea 2.7%, chlamydial infection 8.0%,
      nonchlamydial nongonococcal urethritis 27.7%, active syphilis 6.9%, hepatitis B
      virus infection 9.1%, herpes simplex virus-2 infection 7.8%, and genital warts
      13.2%. CONCLUSIONS: : Given that HIV prevalence among MSM in some other parts of
      China has been as high as 3%, STDs facilitate the transmission of HIV, and high
      prevalence of STDs and sexual risk behaviors among MSM exist in Jiangsu Province,
      the potential for the future spread of HIV is of concern, and it is urgent to
      provide MSMs with STD healthcare services and HIV/AIDS/STD prevention education
      and intervention.

PMID- 16432485
TI  - Consideration for Empiric Trichomonas vaginalis treatment among selected high
      risk HIV-infected female populations with concurrent Neisseria gonorrhea or
      Chlamydia trachomatis cervical infections.

PMID- 16432486
TI  - Sexually transmitted diseases in the Southeastern United States: location, race,
      and social context.
AB  - Heterosexual transmission of HIV in the United States appears to be following the
      epidemiologic pattern of bacterial sexually transmitted diseases (STDs) such as
      syphilis and gonorrhea, disproportionately affecting blacks in the Southeastern
      region. Nationwide, rates of syphilis and gonorrhea are nearly 30 times higher in
      blacks than in whites, and this racial disparity underlies most of the regional
      and county-level differences in rates. The racial disparity cannot be explained
      by traditional measures of socioeconomic differences, and it cannot be explained
      by individual-level determinants of sexual behavior, but rather reflects deeper
      group-level social and environmental factors for which race is a marker. A
      theoretical model based on previous ecologic studies is proposed to explain the
      relationship between racial discrimination and elevated rates of STDs in blacks.
      Key factors in the model include: 1) chronic joblessness, 2) drug and alcohol
      marketing, 3) social disorganization (or social capital), and 4) male
      incarceration.

PMID- 16432488
TI  - Hereditary hemochromatosis: genetics, pathogenesis, and clinical management.
AB  - Recent findings have led to major advances in our understanding of genetics and
      pathophysiology of hereditary hemochromatosis. Many crucial genes and molecules
      have come to light, and the complex interrelationships between them are being
      studied. However, several questions still remain unanswered. Availability of
      genotyping has changed the approach to diagnosis, and serum markers hold promise
      for prognostication. However, the effectiveness of population screening continues
      to be an area of controversy.Finally, there is a promise of development of newer
      therapeutic modalities based on our understanding of the mechanism of iron
      absorption. In this review, we describe the current state of understanding in the
      clinical features, pathophysiology and treatment of hereditary hemochromatosis.

PMID- 16432489
TI  - The endocannabinoid system in chronic liver disease.
AB  - Despite the public concern about the controversial use and abuse of marijuana,
      the scientific community has focused on the therapeutic potentials of cannabinoid
      compounds and had highlighted the importance of endocannabinoids and their
      receptors in physiology and disease. Endocannabinoids have been shown to be
      important mediators in neuroendocrine and psychiatric processes such as food
      intake, drug reward and energy metabolism. Cannabinoid receptors are expressed by
      several cell lines in the liver, such as hepatocytes, myofibroblastic cells,
      endothelial cells and probably cholangiocytes. A perpetuating role in liver
      damage for the endocannabinoid system has been proposed in several steps of
      chronic liver disease progression. Being a major cause of death worldwide,
      chronic liver disease is an important problem. New therapies are needed in order
      to stop or slow damage progression. This review summarizes the results of
      experimental studies involving the endocannabinoid system in liver disease and
      their clinical and therapeutical implications in hepatology.

PMID- 16432490
TI  - Autoimmune-type chronic active hepatitis in children. A report of 23 cases at a
      Hospital in Northwestern Mexico.
AB  - INTRODUCTION: Autoimmune type chronic active hepatitis (AI-CAH) is a rare
      pediatric disorder whose principal characteristics include hepatocellular
      dysfunction and active tissue damage with evolution to cirrhosis in 25-30% of
      cases. OBJECTIVE: Our aim was to ascertain the evolution of 23 children with AI
      CAH treated between 1978 and 2004 at the Hospital Infantil del Estado de Sonora
      in the Sonora State capital of Hermosillo in northern Mexico. MATERIALS AND
      METHODS: We conducted a retrospective review that included the following
      variables: age; sex; personal antecedents; signs and symptoms; laboratory and
      medical office studies; histologic tissue pattern obtained by biopsy; treatment;
      evolution, and mortality. RESULTS: Thirteen males and 10 females participated in
      the study; predominant signs were hyporexia, fatiguehepatomegalia, and icterus.
      Ten patients presented moderate anemia and six patients, leukopenia and
      thrombocytopenia. Eighteen patients presented hypergammaglobulinemia. Twenty
      three patients had percutaneous (p.c.) liver biopsy, and we observed the
      following histologic pattern: rupture of the limiting plate; necrotic foci;
      cholangiolar proliferation, and fibrotic bridges; in addition, four patients
      demonstrated precirrhotic changes. Twenty one children received prednisone for
      periods of between 1 and 12 years; in seven cases, children were administered
      azatioprine. Six children presented histologic, biochemical, and clinical
      remission, nine experienced biochemical remission but presented inflammatory
      activity,five abandoned treatment, and three died due to cirrhosis, liver
      insufficiency, and other complications. DISCUSSION: To date, AI-CAH etiology
      continues to be unknown, while treatment has not been importantly modified in 50
      years and continues to consist of prednisone alone or in association with
      azathioprine.

PMID- 16432491
TI  - Liver dysfunction in steady state sickle cell disease.
AB  - The liver is one of the organs involved in the multiorgan failure that occurs in
      sickle cell disease, the pathophysiology of liver disease in this condition is
      complex because of the interrelated multifactorial causes. Liver dysfunction was
      assessed in both paediatric and adult sickle cell disease patients in the steady
      state. The transaminases and alkaline phosphatase were analysed by automation
      while coagulation studies were done manually. The mean (range) of Alanine
      transaminase (ALT), Aspartate transaminase (AST) and alkaline phosphatase (ALP)
      were 23.0 (2-77) IU, 48.5 (15-120) IU, 227.5 (37-1200) IU respectively. ALT and
      AST levels were less than 100 IU in over 95% of the patients. The gender or age
      of the patients did not significantly affect the level of these three enzymes.
      There was close association between the liver size and elevation of the liver
      enzymes except for alkaline phosphatase (ALT=.017, AST=.009, ALP=.056). Twenty
      five percent of the patients had normal enzymes while 13% had derangement of the
      three enzymes, 19%, 50% and 74% had abnormal ALT, AST and ALP respectively. Only
      22% and 5% had deranged PT and APTT respectively. In conclusion minimal elevation
      of the tramsaminases which is not gender or age dependent were observed in steady
      state sickle cell disease, higher levels of alkaline phosphatase may be due to
      associated vasoocclussive crises involving the bones rather than a pathology of
      the liver.

PMID- 16432492
TI  - A new insight into the differences among non-cirrhotic and cirrhotic patients
      using the liver disease quality of life instrument (LDQOL).
AB  - Our aims were to validate the Brazilian Portuguese version of the Liver Disease
      Quality of Life Questionnaire instrument (LDQOL1.0) and evaluate this tool in non
      cirrhotic patients. METHODS: The LDQOL1.0 consists of the SF-36 generic measure
      of health-related quality of life (HRQOL) and 12 disease-specific dimensions for
      patients with liver disease. The Brazilian Portuguese version instrument was
      administered to 103 patients with liver disease. Reliability was analyzed by
      studying the internal consistency of the individual disease- specific dimensions
      of the LDQOL, as well as by studying the test-retest reliability in a sub-group
      of 74 patients who completed the questionnaire on two occasions 1 to 2 weeks
      apart. Validity was analyzed by determining the instrument's ability to
      discriminate between groups of patients according to severity of the liver
      disease. RESULTS: Internal consistency in the disease- specific dimensions was
      good (CACs 0.66-0.94), as well as test-retest reliability in all dimensions (ICCs
      of 0.64-0.96) p<0.05. We found statistically significant differences in six
      domains when compensated cirrhotic patients, Child A, were compared with non
      cirrhotic patients. We also found statistically significant differences when we
      compared cirrhotic patients evaluated assessed by Child-Pugh and Meld
      classifications. Patients with Child C and Meld>or=15 showed worse quality of
      life. Moderate ceiling and floor effects were found in some disease-specific
      dimensions. IN CONCLUSIONS: the Brazilian Portuguese version of the LDQOL 1.0 is
      very useful for measuring HRQOL in liver diseases.

PMID- 16432493
TI  - Surgical treatment of hydatid cyst of the liver: drainage versus omentoplasty.
AB  - BACKGROUND: Liver is the most common site of infection and several methods of
      surgery have been described to treat this common disease. In this study we aim to
      compare the results of two common methods of surgery; simple drainage versus
      omentoplasty. METHODS: In this prospective study 65 patients with hepatic hydatid
      cyst underwent surgery from 10 May 1995 to 1 July 2002. 35 patients were treated
      with omentoplasty(group I) and 30 of them were treated with drainage(group II).
      The results of surgery including mortality, complications and recurrences were
      recorded. RESULTS: There was no case of mortality in each group of patients.
      Postoperative complications were seen in 5.7% of group I, 16.6% of group II
      patients. The mean duration of hospital stay was 6.5 and 15.6 days in group I and
      group II patients. During a mean period of 18.6 month follow up there was no
      recurrence in each group of patients. CONCLUSION: According to the results of
      this study we suppose that omentoplasty of cyst cavity--if feasible--is preferred
      to tube drainage.

PMID- 16432494
TI  - Performance of the serologic and molecular screening of blood donations for the
      hepatitis B and C viruses in a Mexican Transfusion Center.
AB  - Nucleic acid-amplification testing (NAT) is not routinely practiced in blood
      banks from most low-income countries. We did an exploratory comparison of the
      performance of the standard immunoassay-based screening tests for the hepatitis B
      (HBV) and C (HCV) viruses with that of NAT, in blood donors. From January 1999 to
      March 2005, 94,806 blood donors were screened for anti-HCV antibodies and for
      hepatitis B surface antigen (HBsAg). Also, an exploratory period of molecular
      screening was carried out on 100 consecutive blood donors to detect HBV DNA and
      HCV RNA by home-made PCR techniques without sera pooling. In the 75-month period
      of serologic screening, HBsAg was detected in 219 donors (0.23%; 95% CI, 0.20-
      0.26%) and anti-HCV antibodies in 922 (0.97%; 95% CI, 0.90-1.03%). The annual
      trend for HBsAg prevalence had a decreasing pattern over the years (p<0.001),
      whereas that for anti-HCV did not (p=0.19). In the molecular screening cohort,
      HBV DNA was detected in one donor (1%; 95% CI, 0-6%) and HCV RNA in another (1%;
      95% CI, 0-6%). All these 100 donors tested negative to HBsAg and anti-HCV. Thus,
      the prevalence of positive results for HBV and HCV did not differ if considering
      immunoassays or NAT; nevertheless, these methods did not coincide in detecting
      HBV or HCV in the molecular screening cohort. In conclusion, NAT can detect cases
      of HBV and HCV infections that standard immunoassay techniques can not, even in a
      highly selected population at low risk, like blood donors. Large-scale studies
      are warranted for NAT to be considered as a systematic method for screening of
      HBV and HCV in Mexican blood banks.

PMID- 16432495
TI  - Frequency of increased aminotransferases levels and associated metabolic
      abnormalities in obese and overweight children of an elementary school in Mexico
      City.
AB  - BACKGROUND: Elevated ALT is an indirect marker of NAFLD in patients with non
      alcohol abuse and without other known causes of chronic hepatitis. Obesity, type
      2 diabetes and some dyslipidemias are associated to this condition. The purpose
      of this study was to determine the frequency of increased aminotransferases and
      associated metabolic anomalies among overweight and obese children. METHODS:
      Children from an elementary school with obesity or overweight were included.
      Medical history and anthropometrics measurements were recorded and serum liver
      function tests, lipid profile, glucose and insulin levels, and HOMA index were
      determined. NAFLD diagnosis was considered in those children with ALT>40 U/L and
      AST/ALT ratio<1 after exclusion of other causes of chronic hepatitis. RESULTS:
      Increase ALT levels (>40 U/L) were found in 34/ 80 (42%) obese and overweight
      children; mean age was 9.5+/-1.1 years and mean BMI of 25.8+/-3. The metabolic
      abnormalities in the study group were similar, there were no differences in
      insulin concentration, insulin resistance determined by HOMA-IR Index, serum
      lipid profile and serum glucose between children with or without increased ALT.
      CONCLUSIONS: The frequency (42%) of elevated ALT levels in children with excess
      body weight in this study was greater to those reported in other pediatric
      populations. There were no differences among the metabolic alterations with or
      without increased ALT; these findings support that the principal pathogenic
      factor involved in the development of the hepatic injury may be located in the
      liver.

PMID- 16432496
TI  - The rolling stone.

PMID- 16432497
TI  - Biliary stricture caused by portal biliopathy: case report and literature review.
AB  - Portal biliopathy is a rare condition that is usually not diagnosed and only in
      few cases causes symptoms. Those symptoms are caused by vascular obstruction of
      the biliary tree in patients with portal hypertension. We report a case of a 29
      years man who presented with history of intermittent jaundice, persistent
      elevation of hepatic function test and hematemesis as a manifestation of portal
      hypertension without liver damage. We present the clinical, radiological and
      pathological characteristics and literature review of the cases that had been
      reported, their diagnoses, treatment and clinical implication.

PMID- 16432498
TI  - Comment on: Ruelas-Villavicencio A L, et. al. "In whom, how and how often is
      surveillance for hepatocellular carcinoma cost-effective?" Ann Hepatol 2004; 3:
      152-9.

PMID- 16432499
TI  - Inhibition of classical PKC isoenzymes downregulates STAT1 activation and iNOS
      expression in LPS-treated murine J774 macrophages.
AB  - Proinflammatory cytokines and bacterial products trigger inducible nitric oxide
      synthase (iNOS) expression and nitric oxide (NO) production in inflammatory and
      tissue cells. In inflammation, NO acts as an important mediator having both
      proinflammatory and destructive effects. Protein kinase C (PKC) is a family of
      serine-threonine protein kinase isoenzymes involved in signal transduction
      pathways related to inflammatory responses. The aim of the present study was to
      investigate the role of classical PKC (cPKC) isoenzymes in the regulation of iNOS
      expression and NO production in murine J774 macrophages and the mechanisms
      involved. RO318220 (inhibits PKCbeta, PKCgamma and PKCvarepsilon), GO6976
      (inhibits cPKC isoenzymes PKCalpha and PKCbeta) and LY333531 (inhibits PKCbeta)
      reduced lipopolysaccharide (LPS)-induced NO production and iNOS expression in a
      dose-dependent manner as did 6 h pretreatment with 1 microM phorbol 12-myristate
      13-acetate (PMA) (which was shown to downregulate PKC expression). PKC inhibitors
      also reduced LPS-induced iNOS mRNA levels, but they did not affect the half-life
      of iNOS mRNA. PKC inhibitors did not alter LPS-induced activation of NF-kappaB as
      measured by electrophoretic mobility shift assay. All PKC inhibitors used and
      pretreatment with 1 microM PMA inhibited signal transducer and activator of
      transcription 1 (STAT1) activation as measured by the translocation of STAT1alpha
      from the cytosol to the nucleus by Western blot. In addition, inhibition of STAT1
      activation by AG-490, an inhibitor of JAK-2, also reduced NO production. These
      results suggest that cPKC isoenzymes, especially PKCbeta, mediate the
      upregulation of iNOS expression and NO production in activated macrophages in an
      NF-kappaB-independent manner, possibly through the activation of transcription
      factor STAT1.

PMID- 16432500
TI  - Cardiac implications for the use of beta2-adrenoceptor agonists for the
      management of muscle wasting.
AB  - There are proposals for the implementation of beta(2)-adrenoceptor agonists for
      the management of muscle wasting diseases. The idea has been initiated by studies
      in animal models which show that beta(2)-adrenoceptor agonists cause hypertrophy
      of skeletal muscle. Their use in clinical practice will also need an
      understanding of possible effects of activation of human heart beta(2)
      adrenoceptors. Consequences could include an increased probability of arrhythmias
      in susceptible patients.

PMID- 16432501
TI  - Systemic administration of beta2-adrenoceptor agonists, formoterol and
      salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses.
AB  - beta(2)-Adrenoceptor agonists provide a potential therapy for muscle wasting and
      weakness, but their use may be limited by adverse effects on the heart, mediated
      in part, by beta(1)-adrenoceptor activation. Two beta(2)-agonists, formoterol and
      salmeterol, are approved for treating asthma and have an extended duration of
      action and increased safety, associated with greater beta(2)-adrenoceptor
      selectivity. The pharmacological profiles of formoterol and salmeterol and their
      effects on skeletal and cardiac muscle mass were investigated in 12-week-old,
      male F344 rats. Formoterol and salmeterol were each administered via daily i.p.
      injection at one of seven doses (ranging from 1 to 2,000 microg kg(-1) day(-1)),
      for 4 weeks. Rats were anaesthetised and the EDL and soleus muscles and the heart
      were excised and weighed. Dose-response curves were constructed based on skeletal
      and cardiac muscle hypertrophy. Formoterol was more potent than salmeterol, with
      a significantly lower ED(50) in EDL muscles (1 and 130 microg kg(-1) day(-1), P
      <0.05), whereas salmeterol had greater intrinsic activity than formoterol in both
      EDL and soleus muscles (12% greater hypertrophy than formoterol). The drugs had
      similar potency and intrinsic activity in the heart, with a smaller leftward
      shift for formoterol than seen in skeletal muscle. A dose of 25 microg kg(-1)
      day(-1) of formoterol elicited greater EDL and soleus hypertrophy than
      salmeterol, but resulted in similar beta-adrenoceptor downregulation. These
      results show that doses as low as 1 microg kg(-1) day(-1) of formoterol can
      elicit significant muscle hypertrophy with minimal cardiac hypertrophy and
      provide important information regarding the potential therapeutic use of
      formoterol and salmeterol for muscle wasting.

PMID- 16432503
TI  - Cu2+ (1,10 phenanthroline)3 is an open-channel blocker of the human skeletal
      muscle sodium channel.
AB  - The formation of disulfide bridges is a classical approach used to study the
      mobility, proximity and distances of residues in a variety of proteins, including
      ligand- and voltage-gated ion channels. We performed patch-clamp studies to
      investigate the interaction of a pair of cysteines introduced into the human
      skeletal muscle voltage-gated Na+ channel (hNa(v)1.4) using the oxidation
      catalyst, Cu2+ (1,10-phenanthroline)3 (CuPhen). Our experiments resulted in a
      surprising finding, a reversible current inhibition of the mutant I1160C/L1482C
      containing two cysteines in the D3/and D4/S4-S5 loops, subjected to oxidative
      cross-linking in the presence of CuPhen. We report here that CuPhen is an open
      channel blocker of both mutant and wild-type (WT) hNa(v)1.4 channels, however,
      for WT channels a more than 10-fold higher concentration was needed to induce the
      same effect. Moreover, 1,10-phenanthroline was capable of blocking Na+ channels
      in the absence of Cu2+ ions. Our results indicate a use- and voltage-dependent
      binding and unbinding of CuPhen, reminiscent of the lidocaine quaternary
      derivative QX-314 and the neurotoxin batrachotoxin. Care should be taken when
      using CuPhen as an oxidizing reagent in cross-linking experiments, since it may
      directly affect channel activity. Our results identify CuPhen (and phenantroline)
      as a novel use-dependent inhibitor of Na+ channels, a mechanism that is shared by
      drugs widely used in the treatment of epilepsy, neuropathic pain, cardiac
      arrhythmia and myotonia. We hypothesize that I1160C in D3/S4-S5 and the
      corresponding L1482C mutation in D4/S4-S5 could allosterically affect a binding
      site located in the inner pore region of the channel.

PMID- 16432502
TI  - Mechanisms of 5-aminolevulinic acid ester uptake in mammalian cells.
AB  - The porphyrin precursor 5-aminolevulinic acid (ALA) is being widely used in
      photodynamic therapy of cancer. Improvement in ALA delivery has been sought
      through the use of ALA derivatives, in particular the esterification of ALA with
      aliphatic alcohols, which in certain cases can improve cellular penetration and
      selectivity. ALA uptake systems appear to be distinctive for each cell type. The
      LM3 mammary adenocarcinoma cell line takes ALA up by BETA transporters. In this
      work, we investigated ALA derivative transport systems through the inhibition of
      radiolabelled ALA uptake in the LM3 cells. We also performed inhibition studies
      of gamma-aminobutyric acid (GABA) uptake. The more lipohilic ALA derivatives
      hexyl-ALA and undecanoyl-ALA inhibit ALA uptake, whereas methyl-ALA, R, S-ALA-2
      (hydroxymethyl)tetrahydropyranyl ester and the dendron aminomethane tris methyl 5
      ALA does not inhibit ALA uptake. A similar pattern was found for GABA, except
      that the dendron inhibited GABA uptake. However, hexyl-ALA and undecanoyl-ALA are
      not taken up by BETA transporters, but by simple diffusion, although they still
      inhibit ALA uptake by binding to the cell membrane. These results show that
      different modifications to the ALA molecule lead to different uptake mechanisms.
      Whereas ALA is taken up by BETA transporters, none of the ALA derivatives shares
      the same mechanism. Knowledge of the mechanisms of ALA derivatives entry into the
      cells is essential to understand and improve ALA-mediated PDT and to the design
      of new ALA derivatives that may be taken up at a higher rate than ALA.

PMID- 16432504
TI  - Compared pharmacology of human histamine H3 and H4 receptors: structure-activity
      relationships of histamine derivatives.
AB  - Various histamine derivatives were investigated at the human H3 receptor (H3R)
      and H4 receptor (H4R) stably expressed in human embryonic kidney (HEK)-293 cells
      using [125I]iodoproxyfan and [3H]histamine binding, respectively. In Tris buffer,
      [3H]histamine binding to membranes of HEK(hH4R) cells was monophasic (K(D) of
      3.8+/-0.8 nM). In phosphate buffer, the Hill coefficient was decreased (n(H) =
      0.5+/-0.1) and a large fraction of the binding was converted into a low-affinity
      component (K(D) = 67+/-27 nM). The inhibition of [3H]histamine binding by two
      agonists, a protean agonist and five antagonists/inverse agonists confirms that
      the potency of many H3R ligands is retained or only slightly reduced at the H4R.
      Histamine derivatives substituted with methyl groups in alpha, beta or N(alpha)
      position of the side chain retained a nanomolar potency at the H3R, but their
      affinity was dramatically decreased at the H4R. With relative potencies to
      histamine of 282 and 0.13% at the H3R and H4R, respectively, (+/-)-alpha,beta
      dimethylhistamine is a potent and selective H3R agonist. Chiral alpha-branched
      analogues exhibited a marked stereoselectivity at the H3R and H4R, the
      enantiomers with a configuration equivalent to L-histidine being preferred at
      both receptors. The methylsubstitution of the imidazole ring was also studied.
      The relative potency to histamine of 4-methylhistamine (4-MeHA) at the H4R (67%)
      was similar to that reported at H2 receptors but, owing to its high affinity at
      the H4R (Ki = 7.0+/-1.2 nM) and very low potency at H1- and H3-receptors, it can
      be considered as a potent and selective H4R agonist. On inhibition of forskolin
      induced cAMP formation, all the compounds tested, including 4-MeHA, behaved as
      full agonists at both receptors. However, the maximal inhibition achieved at the
      H4R (approximately -30%) was much lower than at the H3R (approximately -80%).
      Thioperamide behaved as an inverse agonist at both receptors and increased cAMP
      formation with the same maximal effect (approximately +25%). In conclusion,
      although the pharmacological profiles of the human H3R and H4R overlap, the
      structure-activity relationships of histamine derivatives at both receptors
      strongly differ and lead to the identification of selective compounds.

PMID- 16432505
TI  - Differential Rho-kinase dependency of full and partial muscarinic receptor
      agonists in airway smooth muscle contraction.
AB  - In airway smooth muscle (ASM), full and partial muscarinic receptor agonists have
      been described to have large differences in their ability to induce signal
      transduction, including Ca2+-mobilization. Despite these differences, partial
      agonists are capable of inducing a submaximal to maximal ASM contraction. To
      further elucidate transductional differences between full and partial muscarinic
      receptor agonists, we investigated the contribution of Rho-kinase (an important
      regulator of Ca2+-sensitization) to methacholine-, pilocarpine- and McN-A-343
      induced bovine tracheal smooth muscle (BTSM) contraction, using the selective Rho
      kinase inhibitor Y-27632. In addition, we measured Ca2+-mobilization and -influx
      in BTSM cells in response to these agonists in the absence and presence of Y
      27632. Whereas treatment with Y-27632 (1 microM) significantly decreased potency
      (pEC50) for all agonists, maximal contraction (Emax) was reduced by 23.4+/-2.8
      and 50.4+/-7.9% for the partial agonists pilocarpine and McN-A-343, respectively,
      but was unaffected for the full agonist methacholine. However, Emax of
      methacholine became Rho-kinase dependent after taking away its receptor reserve
      using the irreversible muscarinic receptor antagonist propylbenzilylcholine
      mustard. Pilocarpine and McN-A-343 induced a very small Ca2+-mobilization and 
      influx as compared to methacholine. In addition, an inverse relationship of these
      two parameters with the Rho-kinase dependency was observed. Interestingly, no
      inhibitory effects of Y-27632 were observed on Ca2+-mobilization and-influx for
      all three agonists, indicating that the effects of Y-27632 on contraction are
      most likely on the level of Ca2+-sensitization. In conclusion, in contrast to the
      full agonist methacholine, the partial muscarinic receptor agonists pilocarpine
      and McN-A-343 are dependent on Rho-kinase for their maximal contractile effects,
      presumably as a consequence of differences in transductional reserve, indicating
      an agonist-dependent role for Rho-kinase in ASM contraction. Moreover, an inverse
      relationship exists between Rho-kinase dependency and both Ca2+-mobilization and
      Ca2+-influx for these agonists.

PMID- 16432506
TI  - Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell
      degranulation.
AB  - The prostanoid, PGE2, is known to inhibit human lung mast cell activity. The aim
      of the present study was to characterize the EP receptor that mediates this
      effect. PGE2 (pEC(50), 5.8+/-0.1) inhibited the IgE-mediated release of histamine
      from mast cells in a concentration-dependent manner. Alternative EP receptor
      agonists were studied. The EP2-selective agonist, butaprost (pEC50, 5.2+/-0.2),
      was an effective inhibitor of mediator release whereas the EP1/EP3 receptor
      agonist, sulprostone, and the EP1-selective agonist, 17-phenyl-trinor-PGE2, were
      ineffective. The DP agonist PGD2, the FP agonist PGF(2alpha), the IP agonist
      iloprost and the TP agonist U-46619 were ineffective inhibitors of IgE-mediated
      histamine release from mast cells. PGE2 induced a concentration-dependent
      increase in intracellular cAMP levels in mast cells. The effects of the EP1/EP2
      receptor antagonist, AH6809, and the EP4 receptor antagonist, AH23848, on the
      PGE2-mediated inhibition of histamine release were determined. AH6809 (pK(B),
      5.6+/-0.1) caused a modest rightward shift in the PGE2 concentration-response
      curve, whereas AH23848 was ineffective. Long-term (24 h) incubation of mast cells
      with either PGE2 or butaprost (EP2 agonist), but not sulprostone (EP1/EP3
      agonist), caused a significant reduction in the subsequent ability of PGE2 to
      inhibit histamine release. Collectively, these data suggest that PGE2 mediates
      effects on human lung mast cells by interacting with EP2 receptors.

PMID- 16432507
TI  - Mechanism of adenosine-induced airways obstruction in allergic guinea pigs.
AB  - Inhaled adenosine induces airway obstruction in asthmatic but not healthy
      subjects, a phenomenon that is also observed in various animal species when they
      are immunised to a relevant antigen, but which does not occur in naive animals.
      The purpose of this study was to investigate the mechanisms of airway
      responsiveness to adenosine receptor agonists in anaesthetised allergic guinea
      pigs. Inhaled adenosine 5'-monophosphate (AMP), the A1-selective adenosine
      receptor agonist N6-cyclopentyladenosine (CPA) and ovalbumin all caused airway
      obstruction in allergic guinea pigs, but not naive animals, as assessed by
      changes in total lung resistance. In contrast, the A(2a)-selective (CGS 21680; 2
      p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxoamido adenosine) and A3
      selective (IB-MECA; 1-deoxy-1-[6-[[3-iodophenyl)-methyl]amino]-9H-purin-9-yl]-N
      methyl-beta-D-ribofuranuronamide) adenosine receptor agonists failed to elicit
      airway obstruction in passively sensitised guinea pigs. Airway obstruction
      induced by AMP or CPA was not inhibited by the H1 receptor antagonist, mepyramine
      (1 mg kg(-1)) in passively sensitised guinea-pigs. In contrast, airway
      obstruction to ovalbumin was significantly inhibited by this antagonist. Airway
      obstruction induced by AMP and CPA was significantly inhibited in sensitised
      animals chronically treated with capsaicin. In contrast, airway obstruction to
      ovalbumin was not inhibited by this treatment. Airway obstruction induced by AMP,
      CPA and ovalbumin was significantly inhibited following bilateral vagotomy or
      pharmacological treatment with atropine (2 mg kg(-1)). Airway obstruction to CPA
      was inhibited by the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX: 0.1-1 mg kg(-1)). In contrast, airway obstruction to
      ovalbumin was not inhibited by this treatment. These observations provide
      evidence indicating that AMP and CPA may induce airway obstruction in sensitised
      guinea pigs by a mechanism unrelated to histamine release from mast cells, but is
      mediated via an adenosine A1-receptor-dependent mechanism. The inhibition of AMP-
      and CPA-induced airway obstruction by atropine, capsaicin and bilateral vagotomy
      suggests a neuronal-dependent mechanism with the particular involvement of
      capsaicin-sensitive nerves.

PMID- 16432508
TI  - Substance P-induced cyclooxygenase-2 expression in human umbilical vein
      endothelial cells.
AB  - Substance P (SP) is a neuropeptide involved in neurogenic inflammation and an
      agonist for NK(1), NK(2), and NK(3) receptors. SP induces prostaglandin (PG)
      production in various cell types, and these eicosanoids are responsible for
      numerous inflammatory and vascular effects. Cyclooxygenase (COX) are needed to
      convert arachidonic acid to PGs. The study evaluated the effect of SP on COX
      expression in human umbilical vein endothelial cells (HUVEC). COX-2 protein
      expression was upregulated by SP with a peak at 100 nM and at 20 h; in the same
      experimental conditions COX-1 protein expression was unchanged. A correlation
      between COX-2 expression and PGI(2) and PGE(2) release was detected.
      Dexamethasone (DEX) inhibited SP-mediated COX-2 expression. Mitogen-activated
      protein kinases (MAPK) p38 and p42/44 were activated by SP, whereas SB202190 and
      PD98059, inhibitors of these kinases, blocked COX-2 expression. 5,5-dimethyl-3-(3
      fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone (DFU), an experimental
      selective COX-2 inhibitor, blocked SP-induced PG release. By RT-PCR and Western
      blot analysis, we demonstrated that NK(1) and NK(2) but not NK(3) receptors are
      present on HUVEC. Selective NK(1) and NK(2) agonists, namely [Sar(9),
      Met(O(2))(11)]SP and [beta-Ala(8)] NKA(4-10), upregulated COX-2 protein
      expression and PG production, whereas senktide (Suc-Asp-Phe-MePhe-Gly-Leu-Met
      NH(2)), a selective NK(3) agonist, was ineffective in this respect. The NK(1)
      selective antagonist L703,606 ((cis)-2-(diphenylmethyl)-N-((2-iodophenyl)-methyl)
      1-azabicyclo(2.2.2)octan-3-amine) and the NK(2) selective antagonist SR 48,968
      ((S)-N-methyl-N-(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4
      dichlorophenyl)butyl) benzamide) competitively antagonised SP-induced effects.
      The study shows HUVEC to possess functional NK(1) and NK(2) receptors, which
      mediate the ability of SP to induce expression of COX-2 in HUVEC, thus showing a
      previously-undetected effect of SP on endothelial cells.

PMID- 16432510
TI  - Pharmacological characterization of endothelin receptors-mediated contraction in
      the mouse isolated proximal and distal colon.
AB  - The study investigated the role of endothelin (ET) and the ET receptor subtypes
      ET(A) and ET(B) in mediating longitudinal contraction in the mouse proximal and
      distal colon. Cumulative concentration-response curves to a range of ET agonists
      (ET-1, ET-2, ET-3, (Ala(1,3,11,13)) ET and IRL 1620) were established by
      administering concentrations ranging from 0.01 nM to 0.3 microM. Concentration
      response curves to ET-1, which exhibits a high affinity for both ET(A) and ET(B)
      receptor subtypes, were also established in the presence of the ET(A) antagonist
      BMS 182874 and the ET(B) antagonist IRL1038. The addition of the selective ET(A)
      receptor antagonist BMS 182874 caused a rightward shift of the concentration
      response curve to ET-1 in both sections of the colon. The ET(B) receptor
      antagonist IRL1038 (0.3-1 microM) did not significantly effect the response to ET
      1 in the proximal colon but caused a significant decrease in response towards
      higher concentrations ranges (>or=3 nM) in the distal colon. A comparison of the
      concentration-response curves to ET-1, ET-2 and ET-3 showed a rank order of
      potency ET-1>or=ET-2>>ET-3 in the proximal colon and ET-1>or=ET-2>or=ET-3 in the
      distal colon. The selective ET(B) receptor agonists, (Ala(1,3,11,13)) ET and IRL
      1620 did not produce any response in the proximal sections of the colon but
      produced a smaller contraction in the distal segments. The data indicate that ET
      can contract the proximal tissues of the mouse colon predominantly via ET(A)
      receptors and in the distal tissues via ET(A) and ET(B) receptors.

PMID- 16432509
TI  - A small molecule, orally active, alpha4beta1/alpha4beta7 dual antagonist reduces
      leukocyte infiltration and airway hyper-responsiveness in an experimental model
      of allergic asthma in Brown Norway rats.
AB  - alpha(4)beta(1) and alpha(4)beta(7) integrins are preferentially expressed on
      eosinophils and mononuclear leukocytes and play critical roles in their
      recruitment to inflammatory sites. We investigated the effects of TR14035, a
      small molecule, alpha(4)beta(1)/alpha(4)beta(7) dual antagonist, in a rat model
      of allergic asthma. Actively sensitized rats were challenged with aerosol antigen
      or saline on day 21, and the responses evaluated 24 and 48-h later. TR14035 (3 mg
      kg(-1), p.o.) was given 1-h before and 4-h after antigen or saline challenge.
      Airway hyper-responsiveness to intravenous 5-hydroxytryptamine was suppressed in
      TR14035-treated rats. Eosinophil, mononuclear cell and neutrophil counts, and
      eosinophil peroxidase and protein content in the bronchoalveolar lavage fluid
      (BALF) were decreased in TR14035-treated rats. Histological study showed a marked
      reduction of lung inflammatory lesions by TR14035. At 24-h postchallenge, antigen
      induced lung interleukin (IL)-5 mRNA upregulation was suppressed in TR14035
      treated rats. By contrast, IL-4 levels in BALF were not significantly affected by
      TR14035 treatment. IL-4 selectively upregulates vascular cell adhesion molecule-1
      (VCAM-1), which is the main endothelial ligand of alpha(4) integrins. Intravital
      microscopy within the rat mesenteric microcirculation showed that 24-h exposure
      to 1 microg per rat of IL-4 induced a significant increase in leukocyte rolling
      flux, adhesion and emigration. These responses were decreased by 48, 100 and 99%,
      respectively in animals treated with TR14035. In conclusion, TR14035, by acting
      on alpha(4)beta(1) and alpha(4)beta(7) integrins, is an orally active inhibitor
      of airway leukocyte recruitment and hyper-responsiveness in animal models with
      potential interest for the treatment of asthma.

PMID- 16432511
TI  - Interspecies pharmacokinetics and in vitro metabolism of SQ109.
AB  - This study aimed at characterizing the interspecies absorption, distribution,
      metabolism and elimination (ADME) profile of N-geranyl-N'-(2-adamantyl)ethane-1,2
      diamine (SQ109), a new diamine-based antitubercular drug. Single doses of SQ109
      were administered (intravenously (i.v.) and per os (p.o.)) to rodents and dogs
      and blood samples were analyzed by liquid chromatography tandem mass spectrometry
      (LC/MS/MS). Based on i.v. equivalent body surface area dose, the terminal half
      life (t1/2) of SQ109 in dogs was longer than that in rodents, reflected by a
      larger volume of distribution (Vss) and a higher clearance rate of SQ109 in dogs,
      compared to that in rodents. The oral bioavailability of SQ109 in dogs, rats and
      mice were 2.4-5, 12 and 3.8%, respectively. After oral administration of
      [14C]SQ109 to rats, the highest level of radioactivity was in the liver, followed
      by the lung, spleen and kidney. Tissue-to-blood ratios of [14C]SQ109 were greater
      than 1. Fecal elimination of [14C]SQ109 accounted for 22.2% of the total dose of
      [14C]SQ109, while urinary excretion accounted for only 5.6%. The binding of
      [14C]SQ109 (0.1-2.5 microg ml-1) to plasma proteins varied from 6 to 23%
      depending on the species (human, mouse, rat and dog). SQ109 was metabolized by
      rat, mouse, dog and human liver microsomes, resulting in 22.8, 48.4, 50.8 or
      58.3%, respectively, of SQ109 remaining after a 10-min incubation at 37 degrees
      C. The predominant metabolites in the human liver microsomes gave intense ion
      signals at 195, 347 and 363m/z, suggesting the oxidation, epoxidation and N
      dealkylation of SQ109. P450 reaction phenotyping using recombinant cDNA-expressed
      human CYPs in conjunction with specific CYP inhibitors indicated that CYP2D6 and
      CYP2C19 were the predominant CYPs involved in SQ109 metabolism.

PMID- 16432512
TI  - Investigation of the role of TASK-2 channels in rat pulmonary arteries;
      pharmacological and functional studies following RNA interference procedures.
AB  - In the present study, we investigated the ability of RNA interference technology
      to suppress TASK-2 potassium channel expression in human embryonic kidney
      (HEK293) cells stably transfected with TASK-2 cDNA and in rat isolated intact
      pulmonary arteries. Lipofectamine-induced transfection of a specific siRNA
      sequence targeted against TASK-2 resulted in a dose- and time-dependent decrease
      in TASK-2 channel protein expression. In siRNA-transfected cells the TASK-2 peak
      currents were significantly smaller than in control cells at every investigated
      pH, while the pH sensitivity was not altered. Using scrambled siRNA as a negative
      control, there were no significant changes in TASK-2 protein expression or
      current compared to mock-transfected cells. In TASK-2 siRNA-transfected small
      pulmonary arteries, but not in scrambled siRNA-treated vessels, myocyte resting
      membrane potential at pH 7.4 was significantly less negative and the
      hyperpolarisations in response to increasing pH from 6.4 to 8.4 were
      significantly smaller compared with control. The application of levcromakalim (10
      microM), NS1619 (33 microM) and a potassium channel inhibitor cocktail (5 mM 4
      aminopyridine, 10 mM tetraethylammonium chloride, 30 microM Ba2+ and 10 microM
      glibenclamide) had similar effects in control and in siRNA-transfected vessels.
      The TASK-1 (anandamide-sensitive) contribution to resting membrane potential was
      comparable in each group. Clofilium (100 microM) generated significantly smaller
      responses in transfected artery segments. These results suggest that RNA
      interference techniques are effective at inhibiting TASK-2 channel expression in
      cultured cells and in intact vessels and that TASK-2 channels have a functional
      role in setting the membrane potential of pulmonary artery myocytes.

PMID- 16432513
TI  - Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity.
AB  - Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostanoid synthesis, has
      been implicated in the neurotoxicity resulting from hypoxia-ischemia, and its
      inhibition has therapeutic potential for ischemic stroke. However, COX-2
      inhibitors increase the risk of cardiovascular complications. We therefore sought
      to identify the downstream effectors of COX-2 neurotoxicity, and found that
      prostaglandin E(2) EP1 receptors are essential for the neurotoxicity mediated by
      COX-2-derived prostaglandin E(2). EP1 receptors disrupt Ca(2+) homeostasis by
      impairing Na(+)-Ca(2+) exchange, a key mechanism by which neurons cope with
      excess Ca(2+) accumulation after an excitotoxic insult. Thus, EP1 receptors
      contribute to neurotoxicity by augmenting the Ca(2+) dysregulation underlying
      excitotoxic neuronal death. Pharmacological inhibition or gene inactivation of
      EP1 receptors ameliorates brain injury induced by excitotoxicity, oxygen glucose
      deprivation and middle cerebral artery (MCA) occlusion. An EP1 receptor inhibitor
      reduces brain injury when administered 6 hours after MCA occlusion, suggesting
      that EP1 receptor inhibition may be a viable therapeutic option in ischemic
      stroke.

PMID- 16432514
TI  - Different strokes for rodent folks.

PMID- 16432515
TI  - NMR mapping of protein interactions in living cells.

PMID- 16432516
TI  - Fluorescence cross-correlation spectroscopy in living cells.
AB  - Cell biologists strive to characterize molecular interactions directly in the
      intracellular environment. The intrinsic resolution of optical microscopy,
      however, allows visualization of only coarse subcellular localization. By
      extracting information from molecular dynamics, fluorescence cross-correlation
      spectroscopy (FCCS) grants access to processes on a molecular scale, such as
      diffusion, binding, enzymatic reactions and codiffusion, and has become a
      valuable tool for studies in living cells. Here we review basic principles of
      FCCS and focus on seminal applications, including examples of intracellular
      signaling and trafficking. We consider FCCS in the context of fluorescence
      resonance energy transfer and multicolor imaging techniques and discuss
      application strategies and recent technical advances.

PMID- 16432517
TI  - Mapping structural interactions using in-cell NMR spectroscopy (STINT-NMR).
AB  - We describe a high-throughput in-cell nuclear magnetic resonance (NMR)-based
      method for mapping the structural changes that accompany protein-protein
      interactions (STINT-NMR). The method entails sequentially expressing two (or
      more) proteins within a single bacterial cell in a time-controlled manner and
      monitoring the protein interactions using in-cell NMR spectroscopy. The resulting
      spectra provide a complete titration of the interaction and define structural
      details of the interacting surfaces at atomic resolution.

PMID- 16432518
TI  - BEAMing up for detection and quantification of rare sequence variants.
AB  - BEAMing allows the one-to-one conversion of a population of DNA fragments into a
      population of beads. We used rolling circle amplification to increase the number
      of copies bound to such beads by more than 100-fold. This allowed enumeration of
      mutant and wild-type sequences even when they were present at ratios less than
      1:10,000 and was sensitive enough to directly quantify the error rate of DNA
      polymerases used for PCR.

PMID- 16432519
TI  - Targeted insult to subsurface cortical blood vessels using ultrashort laser
      pulses: three models of stroke.
AB  - We present a method to produce vascular disruptions within rat brain parenchyma
      that targets single microvessels. We used two-photon microscopy to image vascular
      architecture, to select a vessel for injury and to measure blood-flow dynamics.
      We irradiated the vessel with high-fluence, ultrashort laser pulses and achieved
      three forms of vascular insult. (i) Vessel rupture was induced at the highest
      optical energies; this provides a model for hemorrhage. (ii) Extravasation of
      blood components was induced near the lowest energies and was accompanied by
      maintained flow in the target vessel. (iii) An intravascular clot evolved when an
      extravasated vessel was further irradiated. Such clots dramatically impaired
      blood flow in downstream vessels, in which speeds dropped to as low as
      approximately 10% of baseline values. This demonstrates that a single blockage to
      a microvessel can lead to local cortical ischemia. Lastly, we show that
      hemodilution leads to a restoration of flow in secondary downstream vessels.

PMID- 16432520
TI  - A versatile tool for conditional gene expression and knockdown.
AB  - Drug-inducible systems allowing the control of gene expression in mammalian cells
      are invaluable tools for genetic research, and could also fulfill essential roles
      in gene- and cell-based therapy. Currently available systems, however, often have
      limited in vivo functionality because of leakiness, insufficient levels of
      induction, lack of tissue specificity or prohibitively complicated designs. Here
      we describe a lentiviral vector-based, conditional gene expression system for
      drug-controllable expression of polymerase (Pol) II promoter-driven transgenes or
      Pol III promoter-controlled sequences encoding small inhibitory hairpin RNAs
      (shRNAs). This system has great robustness and versatility, governing tightly
      controlled gene expression in cell lines, in embryonic or hematopoietic stem
      cells, in human tumors xenotransplanted into nude mice, in the brain of rats
      injected intraparenchymally with the vector, and in transgenic mice generated by
      infection of fertilized oocytes. These results open up promising perspectives for
      basic or translational research and for the development of gene-based
      therapeutics.

PMID- 16432521
TI  - Microarrays of lentiviruses for gene function screens in immortalized and primary
      cells.
AB  - Here we describe lentivirus-infected cell microarrays for the high-throughput
      screening of gene function in mammalian cells. To create these arrays, we
      cultured mammalian cells on glass slides 'printed' with lentiviruses pseudotyped
      as vesicular stomatitis virus glycoprotein, which encode short hairpin RNA or
      cDNA. Cells that land on the printed 'features' become infected with lentivirus,
      creating a living array of stably transduced cell clusters within a monolayer of
      uninfected cells. The small size of the features of the microarrays (300 microm
      in diameter) allows high-density spotting of lentivirus, permitting thousands of
      distinct parallel infections on a single glass slide. Because lentiviruses have a
      wide cellular tropism, including primary cells, lentivirus-infected cell
      microarrays can be used as a platform for high-throughput screening in a variety
      of cell types.

PMID- 16432522
TI  - Immuno-spin trapping of DNA radicals.
AB  - The detection of DNA radicals by immuno-spin trapping (IST) is based on the
      trapping of radicals with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), forming stable
      nitrone adducts that are then detected using an anti-DMPO serum. DNA radicals are
      very reactive species, and because they are paramagnetic they have previously
      been detected only by electron spin resonance (ESR) with or without spin
      trapping, which is not available in most bioresearch laboratories. IST combines
      the simplicity, reliability, specificity and sensitivity of spin trapping with
      heterogeneous immunoassays for the detection of DNA radicals, and complements
      existing methods for the measurement of oxidatively generated DNA damage. Here we
      have used IST to demonstrate that DMPO traps Cu(II)-H(2)O(2)-induced DNA radicals
      in situ and in real time, forming DMPO-DNA nitrone adducts, but preventing both 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) formation and DNA fragmentation. We
      also applied IST to detect DNA radicals in rat hepatocytes exposed to Cu(II) and
      H(2)O(2) under nonlethal conditions.

PMID- 16432523
TI  - A visual thalamocortical slice.
AB  - We describe a thalamocortical slice preparation in which connectivity between the
      mouse lateral geniculate nucleus (LGN) and primary visual cortex (V1) is
      preserved. Through DiI injections in fixed brains we traced and created a three
      dimensional model of the mouse visual pathways. From this computer model we
      designed a slice preparation that contains a projection from LGN to V1. We
      prepared brain slices with these predicted coordinates and demonstrated
      anatomical LGN-V1 connectivity in these slices after LGN tracer injections. We
      also revealed functional LGN-V1 connectivity by stimulating LGN electrically and
      detecting responses in layer 4 of V1 using calcium imaging, field potential
      recordings and whole-cell recordings. We also identified layer-4 neurons that
      receive direct thalamocortical input. Finally, we compared cortical activity
      after LGN stimulation with spontaneous cortical activity and found significant
      overlap of the spatiotemporal dynamics generated by both types of events.

PMID- 16432524
TI  - Protein-protein interaction assays: eliminating false positive interactions.

PMID- 16432526
TI  - The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS): an instrument
      for assessing obsessive-compulsive symptom dimensions.
AB  - Obsessive-compulsive disorder (OCD) encompasses a broad range of symptoms
      representing multiple domains. This complex phenotype can be summarized using a
      few consistent and temporally stable symptom dimensions. The objective of this
      study was to assess the psychometric properties of the Dimensional Yale-Brown
      Obsessive-Compulsive Scale (DY-BOCS). This scale measures the presence and
      severity of obsessive-compulsive (OC) symptoms within six distinct dimensions
      that combine thematically related obsessions and compulsions. The DY-BOCS
      includes portions to be used as a self-report instrument and portions to be used
      by expert raters, including global ratings of OC symptom severity and overall
      impairment. We assessed 137 patients with a Diagnostic and Statistical Manual-IV
      diagnosis of OCD, aged 6-69 years, from sites in the USA, Canada and Brazil.
      Estimates of the reliability and validity of both the expert and self-report
      versions of the DY-BOCS were calculated and stratified according to age
      (pediatric vs. adult subjects). The internal consistency of each of the six
      symptom dimensions and the global severity score were excellent. The inter-rater
      agreement was also excellent for all component scores. Self-report and expert
      ratings were highly intercorrelated. The global DY-BOCS score was highly
      correlated with the total Yale-Brown Obsessive-Compulsive Scale score (Pearson r
      = 0.82, P<0.0001). Severity scores for individual symptom dimensions were largely
      independent of one another, only modestly correlated with the global ratings, and
      were also differentially related to ratings of depression, anxiety and tic
      severity. No major differences were observed when the results were stratified by
      age. These results indicate that the DY-BOCS is a reliable and valid instrument
      for assessing multiple aspects of OCD symptom severity in natural history,
      neuroimaging, treatment response and genetic studies when administered by expert
      clinicians or their highly trained staff.

PMID- 16432527
TI  - Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of
      correlation with the polymorphism SERTLPR.
AB  - An insertion/deletion polymorphism in the SERT linked promoter region (SERTLPR),
      previously reported to regulate mRNA expression in vitro, has been associated
      with mental disorders and response to psychotropic drugs. Contradictory evidence,
      however, has raised questions about the role of SERTLPR in regulating mRNA
      expression in vivo. We have used analysis of allelic expression imbalance (AEI)
      of SERT mRNA to assess quantitatively the contribution of SERTLPR to mRNA
      expression in human post-mortem pons tissue sections containing serotonergic
      neurons of the dorsal and median raphe nuclei. Any difference in the expression
      of one allele over the other indicates the presence of cis-acting elements that
      differentially affect transcription and/or mRNA processing and turnover. Using a
      marker SNP in the 3' untranslated region of SERT mRNA, statistically significant
      differences in allelic mRNA levels were detected in nine out of 29 samples
      heterozygous for the marker SNP. While the allelic expression differences were
      relatively small (15-25%), they could nevertheless be physiologically relevant.
      Although previous results had suggested that the long form of SERTLPR yields
      higher mRNA levels than the short form, we did not observe a correlation between
      SERTLPR and allelic expression ratios. Also in contrast to previous results, we
      found no correlation between SERTLPR and allelic expression ratios or SERT mRNA
      levels in B-lymphocytes. This study demonstrates that regulation of SERT mRNA is
      independent of SERTLPR, but could be associated with polymorphisms in partial
      linkage disequilibrium with SERTLPR.

PMID- 16432528
TI  - Treatment-resistant bipolar disorder.
AB  - Despite the remarkable increase in medications validated as effective in bipolar
      disorder, treatment is still plagued by inadequate response in acute manic or
      depressive episodes or in long-term preventive maintenance treatment. Established
      first-line treatments include lithium, valproate and second-generation
      antipsychotics (SGAs) in acute mania, and lithium and valproate as maintenance
      treatments. Recently validated treatments include extended release carbamazapine
      for acute mania and lamotrigine, olanzapine and aripiprazole as maintenance
      treatments. For treatment-resistant mania and as maintenance treatments, a number
      of newer anticonvulsants, and one older one, phenytoin, have shown some promise
      as effective. However, not all anticonvulsants are effective and each agent needs
      to be evaluated individually. Combining multiple agents is the most commonly used
      clinical strategy for treatment resistant bipolar patients despite a relative
      lack of data supporting its use, except for acute mania (for which lithium or
      valproate plus an SGA is optimal treatment). Other approaches that may be
      effective for treatment-resistant patients include high-dose thyroid
      augmentation, clozapine, calcium channel blockers and electroconvulsive therapy
      (ECT). Adjunctive psychotherapies show convincing efficacy using a variety of
      different techniques, most of which include substantial attention to education
      and enhancing coping strategies. Only recently, bipolar depression has become a
      topic of serious inquiry with the dominant controversy focusing on the place of
      antidepressants in the treatment of bipolar depression. Other than mood
      stabilizers alone or the combination of mood stabilizers and antidepressants,
      most of the approaches for treatment-resistant bipolar depression are relatively
      similar to those used in unipolar depression, with the possible exception of a
      more prominent place for SGAs, prescribed either alone or in combination with
      antidepressants. Future work in the area needs to explore the treatments commonly
      used by clinicians with inadequate research support, such as combination therapy
      and the use of antidepressants as both acute and adjunctive maintenance
      treatments for bipolar disorder.

PMID- 16432529
TI  - Depressive symptoms of patients using clean intermittent catheterization for
      neurogenic bladder secondary to spinal cord injury.
AB  - STUDY DESIGN: Prospective, cross-sectional study, based on cases of spinal cord
      injury (SCI). SETTING: Three outpatient medical departments in Seoul, Korea.
      OBJECTIVES: To assess depressive symptoms in patients on clean intermittent
      catheterization after SCI. METHODS: In total, 102 subjects (68 males and 34
      females, mean age 39.5 with a range of 18-75 years) were included in the primary
      analysis. A control group of 110 was selected from the routine health checkup.
      All subjects completed the Beck Depression Inventory (BDI). RESULTS: For patients
      and controls, the average total BDI scores were 20.3+/-1.0 and 11.4+/-0.5,
      respectively (P<0.001). With regard to severity of depression among patient
      groups, three (3.0%) reported normal; four (3.9%) reported mild to moderate
      depression; 24 (23.5%) reported moderate to severe depression; and 71 (69.6%)
      reported severe depression. On the multivariate logistic regression analysis, a
      positive association with the risk of depression was observed in gender and type
      of catheterization. Female patients had a 3.8-fold higher risk (odds ratio (OR)
      13.83; 95% confidence interval (CI) 1.42-10.31; P=0.008) of depression than male
      patients. In the same model, patients who were unable to perform catheterization
      independently had a 4.6-fold higher risk (OR 4.62; 95% CI 1.67-12.81, P=0.003) of
      depression than those who were able to perform self-catheterization. CONCLUSIONS:
      The results demonstrate that the patients with neurogenic bladder secondary to
      SCI have higher degrees of depression than normal population. In addition, our
      findings also suggest that depression is closely related to gender and patient's
      ability to perform self-catheterization.

PMID- 16432530
TI  - Electrophysiological changes in isolated spinal cord white matter in response to
      oxygen deprivation.
AB  - STUDY DESIGN: In vitro studies using isolated guinea pig spinal cord white
      matter. OBJECTIVES: To determine whether lack of oxygen can cause irreversible
      impairment of electrical impulse conduction. SETTING: Department of Basic Medical
      Sciences, Purdue University, West Lafayette, Indiana, USA. METHODS: The hypoxic
      injury was induced by reducing the oxygen tension of the perfused solution by
      80%. Compound action potentials (CAPs) were monitored before, during, and after
      oxygen deprivation. RESULTS: We have found that 60 min of hypoxia reduced the
      conduction to 30% of preinjury level and recovered to approximately 60% of the
      preinjury level upon reoxygenation. Larger axons appeared to be more vulnerable
      to oxygen deprivation. We noted a significant decrease and recovery of the
      depolarizing afterpotential (DAP). Likewise, there was a delay and recovery of
      absolute and relative refractory period. Concomitantly, the ability of axons to
      follow repetitive stimuli was suppressed following oxygen deprivation but
      recovered upon reoxygenation. CONCLUSION: Following 60 min of oxygen deprivation
      and 30 min of reoxygenation, mammalian spinal cord white matter can partially
      recover electrical impulse conduction. However, within the same period, cords
      gained a complete recovery of other electrical properties, such as the depression
      of DAP, the delaying of refractory period, and the decreased ability to respond
      to repetitive stimuli. Compared to previous findings when both oxygen and glucose
      were deprived, we conclude that glucose plays a relatively minor role during the
      acute stage of oxygen deprivation in mammalian spinal cord white matter.

PMID- 16432532
TI  - Thermal perception thresholds: assessing the level of human spinal cord injury.
AB  - STUDY DESIGN: Controlled, cross-sectional, observational. OBJECTIVES: To
      investigate whether quantitative sensory testing (QST) is able to reveal
      subclinical deficits at the neurological level of lesion in subjects with chronic
      spinal cord injury (SCI). SETTING: National Spinal Injuries Centre, Stoke
      Mandeville Hospital and Imperial College London, UK. METHODS: QST and clinical
      assessments were carried out on 18 subjects with complete SCI (American Spinal
      Injury Association (ASIA) grade A) and 10 subjects with incomplete SCI (ASIA
      grades B, C or D). A total of 10 healthy subjects acted as controls. RESULTS: At
      the level of lesion perceptual thresholds to monofilaments, cold pain and heat
      pain were similar to values in control subjects but cool and warm thresholds were
      significantly raised. A correlation between cool and warm thresholds was observed
      at the level of lesion in complete SCI and between heat and cold pain thresholds
      at the level of lesion in complete SCI, incomplete SCI and in control subjects.
      In the zone of partial preservation in complete SCI and below the level of lesion
      in incomplete SCI, thresholds for all modalities were all different compared to
      controls. CONCLUSION: QST reveals impaired thermal sensation in dermatomes
      clinically defined as normal with ASIA standards. Quantitative thermal testing
      therefore permits a discriminating assessment of preserved sensation and
      subclinical deficit and has the potential to improve upon the clinical detection
      of natural recovery or changes in level of injury following interventions
      designed to repair SCI.

PMID- 16432531
TI  - Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord
      excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and
      myeloperoxidase content in a pig model of acute spinal cord injury.
AB  - STUDY DESIGN: Prospective, randomized, in vivo acute spinal cord injury in pigs.
      SETTING: Department of Anesthesiology, University of Washington, Seattle, WA,
      USA. OBJECTIVES: To determine whether postinjury methylprednisolone could reduce
      the generation of known mediators of secondary neurological injury. METHODS:
      Intrathecal microdialysis probes were used to sample cerebrospinal fluid (CSF)
      for measurement of PGE(2), glutamate, and citrulline (a byproduct of nitric oxide
      generation), before and after spinal cord injury in anesthetized pigs. The spinal
      cord was removed at the end of the study for measurement of myeloperoxidase and
      methylprednisolone concentrations. Animals were randomly allocated to receive
      intravenous methylprednisolone (30 mg/kg bolus then 3.4 mg/kg/h), intrathecal
      methylprednisolone (5 mg bolus then 5 mg/h), or saline, beginning 30 min after
      the spinal cord was injured by using a modification of the Allen weight drop
      technique. RESULTS: Spinal cord injury significantly increased the amount of
      glutamate, PGE(2), myeloperoxidase, and citrulline, recovered from the CSF
      dialysates. However, neither intravenous nor intrathecal methylprednisolone
      administered after injury had any effect on the magnitude of the increase in any
      of the measured biochemicals. Intrathecal methylprednisolone administration
      produced a spinal cord methylprednisolone concentration that was eight times
      greater, and a plasma concentration that was 32 times less, than that achieved
      with intravenous administration. CONCLUSIONS: Contrary to earlier animal studies
      in which methylprednisolone was administered either before or immediately after
      spinal cord injury, we found no effect of intravenous or intrathecal
      methylprednisolone on any of the parameters measured when administered 30 min
      postinjury.

PMID- 16432533
TI  - Gynecomastia in patients with prostate cancer: update on treatment options.
AB  - Non-steroidal antiandrogen monotherapy offers potential quality of life benefits
      over other treatment modalities in patients with prostate cancer. Nevertheless,
      gynecomastia and breast pain still represent the most bothersome side effects
      during this treatment. In this update article, recent advances in the management
      options for gynecomastia/breast pain caused by hormonal manipulation are reviewed
      and critically analyzed.

PMID- 16432534
TI  - Effects of geldanamycin on HIF-1alpha mediated angiogenesis and invasion in
      prostate cancer cells.
AB  - Geldanamycin (GA), a benzoquinone ansamycin, is a naturally occurring inhibitor
      of heat shock protein (Hsp90), which regulates the transcription activity of
      hypoxia-inducible factor 1 (HIF-1alpha). Under hypoxia, HIF-1alpha is activated
      in tumor cells, and induces the transcription of vascular endothelial growth
      factor (VEGF), which is the prime regulator for angiogenesis. VEGF promotes the
      formation of new blood vessels by stimulating endothelial cell division and
      migration. This eventually forms a vascular network that allows for tumor growth
      and metastasis. In this study, we used GA to inhibit HIF-1alpha transcription
      function. Human prostate cancer DU-145 cells were incubated in a hypoxic chamber
      at 1% O(2) and 37 degrees C for different durations. Both mRNA and protein levels
      of HIF-1alpha and VEGF were upregulated under hypoxic conditions. We demonstrated
      that GA treatment of hypoxic DU-145 cells abolished the induction of HIF-1alpha
      protein in a time-dependent manner and decreased VEGF mRNA and its protein
      levels. The transient transfection of DU-145 cells with luciferase reporter gene
      construct (5HRE/hCMVmp-luc) showed that the transcriptional activity of HIF
      1alpha was significantly induced in response to hypoxia, but inhibited by GA. In
      addition, using conditioned medium from GA-treated hypoxic cells led to a
      significant decrease in cell invasion in comparison with using conditioned medium
      from nontreated hypoxic cells. These data provide evidence for the important role
      of GA in inhibition of angiogenesis and also invasion mediated by HIF-1alpha in
      prostate cancer cells.

PMID- 16432535
TI  - Microarray expression profiles of angiogenesis-related genes predict tumor cell
      response to artemisinins.
AB  - Artemisinin (ARS) and its derivatives are used for the second-line therapy of
      malaria infections with Plasmodium falciparum and P. vivax. ARSs also reveal
      profound antitumor activity in vitro and in vivo. In the present investigation,
      we correlated the mRNA expression data of 89 angiogenesis-related genes obtained
      by microarray hybridization from the database of the US National Cancer Institute
      with the 50% growth inhibition concentration values for eight ARSs (ARS,
      arteether (ARE), artesunate (ART), artemisetene, arteanuine B,
      dihydroartemisinylester stereoisomers 1 and 2). The constitutive expression of 30
      genes correlated significantly with the cellular response to ARSs. By means of
      hierarchical cluster analysis and cluster image mapping expression, profiles were
      identified that determined significantly the cellular response to ART, ARE,
      artemether and dihydroartemisinylester stereoisomer 1. We have exemplarily
      validated the microarray data of six out of these 30 genes by real-time RT-PCR in
      seven cell lines. The fact that sensitivity and resistance of tumor cells could
      be predicted by the mRNA expression of angiogenesis-related genes indicate that
      ARSs reveal their antitumor effects at least in part by inhibition of tumor
      angiogenesis. As many chemopreventive drugs exert antiangiogenic features, ARSs
      might also be chemopreventive in addition to their cytotoxic effects.

PMID- 16432536
TI  - Complexity of attrition in the treatment of obesity: clues from a structured
      telephone interview.
AB  - OBJECTIVES: To investigate the causes of attrition reported by obese patients
      treated by medical centres. DESIGN: Observational study. SETTING: Obese patients
      enrolled in a long-term study involving 18 Italian medical centres. PARTICIPANTS:
      A total of 940 obese patients (727 female; mean age, 49 years; mean BMI, 38.6
      kg/m2). MEASUREMENTS: Causes of attrition reported by dropouts during a
      structured telephone interview. RESULTS: After a median observation period of 41
      months (range, 25-50), 766 of 940 patients (81.5%) discontinued treatment. Sixty
      two per cent of total dropout occurred in the first year of follow-up. Seventy
      four per cent of dropouts reported a single primary reasons for treatment
      interruption. Two primary reasons were reported by 22.4% of patients, and three
      reasons by 3.4%. Practical difficulties, alone or in combination, were reported
      by more than half of dropouts (55%), and were the leading cause of attrition
      followed by perceived failure of treatment. Among practical difficulties, family
      problems or problems at work and logistics, coupled with health problems other
      than obesity, were the most frequent reasons of attrition, but also a perceived
      sense of abandonment or a bad interaction with therapists were frequently
      reported. CONCLUSION: Practical difficulties and psychological problems are the
      most important reasons of attrition reported by patients. A therapeutic alliance
      addressing these issues has a large potential to reduce treatment interruption
      and to improve outcome in obesity.

PMID- 16432537
TI  - Waist circumference and BMI are independently associated with the variation of
      cardio-respiratory and neuromuscular fitness in young adult men.
AB  - OBJECTIVE: To test two hypotheses: (1) cardiorespiratory (CRF) and neuromuscular
      (NMF) fitness is associated with body mass index (BMI) and waist circumference
      (WC), independent of each other and of leisure-time physical activity; (2)
      individuals with high CRF and NMF have lower WC for a given BMI, compared with
      those with low CRF and NMF. DESIGN: Cross-sectional study. SETTING: Men
      participating in refresher training organized by the Finnish Defence Forces.
      PARTICIPANTS: A total of 951 men (mean age 29.1, s.d. 4.2 years; BMI 25.3
      kg/m(2), s.d. 3.8; WC 91, s.d. 11 cm). MAIN OUTCOME MEASURES: Body mass index,
      WC, maximal oxygen uptake (VO(2)max), height of vertical jump, number of push-ups
      and sit-ups during a 1-min test, static back extension endurance, isometric grip
      strength, self-reported leisure-time vigorous physical activity. Multiple linear
      regressions were used to explain the variation in fitness. RESULTS: Waist
      circumference had significant (P<0.001) negative association with all test
      results (standardized beta coefficients from -0.23 to -0.77), except for grip
      strength. Body mass index had significant negative association with VO(2)max (
      0.12; P<0.05), but positive association (P<0.01) with grip strength (0.28),
      vertical jump (0.21) and push-ups (0.55). For a given BMI, the estimated WC was
      highest among those with the poorest results for VO(2)max, vertical jump, sit-ups
      and push-ups. CONCLUSIONS: Despite stronger isometric grip strength, the
      functional muscle fitness of the upper body, trunk and lower extremities is
      impaired in individuals with abdominal obesity. Although the known loss of CRF is
      a serious consequence of obesity, the deterioration of NMF deserves increased
      attention.

PMID- 16432538
TI  - Insulin resistance, obesity, and metabolic syndrome among non-diabetic pre- and
      post-menopausal women in North Taiwan.
AB  - OBJECTIVE: To investigate the relationship between the metabolic syndrome and its
      related factors among non-diabetic pre- and post-menopausal women in North
      Taiwan. DESIGN: A cross-sectional study in a medical center in North Taiwan.
      SUBJECTS: Five hundred and ninety-four, non-diabetic middle-aged women (age
      range=40-64 years, mean=48.9+/-5.4 years) were recruited. MEASUREMENTS: The
      fasting plasma glucose, insulin, lipids levels and anthropometric indices were
      measured. The homeostasis model assessment was applied to estimate the degree of
      insulin resistance (HOMA-IR). Metabolic syndrome was defined by using the
      National Cholesterol Education Panel (NCEP) criteria and modified NCEP criteria
      (waist circumference >80 cm). RESULTS: The prevalence of metabolic syndrome was
      6.2% using NCEP criteria, and 8.9% using modified NCEP criteria. Post-menopausal
      women had a higher prevalence of metabolic syndrome and its individual components
      compared to pre-menopausal women except hyperglycemia and low HDL-C. In multiple
      logistic regression analysis with adjustment for age and menopausal status, both
      BMI and HOMA-IR were independently associated with the metabolic syndrome.
      CONCLUSION: The prevalence of metabolic syndrome was higher in post-menopausal
      than pre-menopausal women. Both obesity and insulin resistance may play an
      important role in the development of metabolic syndrome among the middle-aged
      women in North Taiwan.

PMID- 16432539
TI  - Lifestyle correlates of anthropometric estimates of body adiposity in an Italian
      middle-aged and elderly population: a covariance analysis.
AB  - OBJECTIVE: To study the relationship between behavioural factors, body adiposity
      and muscle mass. SUBJECTS AND METHODS: A total of 1415 Italian individuals (705
      men and 710 women) aged 40-74 years from a population-based survey carried out in
      the town of Bollate (Milan). Analysis of covariance was used to refine and
      improve the precision of the comparisons. RESULTS: Men: Smoking and sedentary
      behaviour were related to larger waist circumference (WC) and smaller hip
      circumference (HC). Increased WC was also associated with high-fat diet and
      moderate-to-heavy drinking (compared to light drinkers). Those more educated
      (completed high school) were leaner and ex-smokers had higher body mass index
      (BMI) than non-smokers. Women: BMI was inversely related with education, the more
      educated having also lower muscle mass. The light drinkers were leaner and
      moderate-to-heavy drinkers had less muscle mass than abstainers. Moderate-to
      heavy drinkers had larger WC than light drinkers. A strong negative trend was
      found in the relationship between dietary fibre and WC. Overall adiposity (BMI)
      and, more weakly, HC and peripheral subcutaneous fat increased with more TV
      watching, whereas BMI lowered, together with WC and muscle mass (as measured by
      the mid-arm circumference), with more walking/cycling. CONCLUSIONS: Modifiable
      habits such as smoking (men) and moderate-to-heavy alcohol drinking are
      associated with a pattern that is particularly deleterious to health: increased
      intra-abdominal fat and less muscle mass. Prevention strategies should be
      simultaneously aimed at promoting physical activities and reducing sedentary
      behaviours. A low-fat, fibre-rich diet seems to be closely related to a healthy
      distribution of body fat.

PMID- 16432540
TI  - The EAT-26 as screening instrument for clinical nutrition unit attenders.
AB  - OBJECTIVE: The aim of this study was to use the Eating Attitudes Test-26 (EAT-26)
      as a screening instrument on a specific population with a marked prevalence of
      binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS).
      The EAT-26 questionnaire was used in order to identify the high-risk subjects for
      referral to clinical evaluation. METHOD: EAT-26 was administered to 845 subjects
      who, for the first time, came to the Nutritional Medicine Service looking for a
      diet between January 1999 and December 2002. From this initial sample,
      subsequently, 250 subjects were randomly selected and administered a
      semistructured clinical interview for DSM-IV (SCID I, version 2.0). RESULTS:
      Discriminant analysis provided a cutoff value of EAT-26=11. Logistic regression
      analysis indicated high Dieting (D) or Bulimia (B) subscale scores as a risk
      factor of EDNOS or bulimia nervosa (BN) cases, respectively; on the other hand, a
      high Oral Control (O) subscale score represented a protecting factor for BED
      cases. CONCLUSION: Our study tried to assess the usefulness of EAT-26 as a
      screening instrument for obese patients attending a Medical Nutritional Service.
      Results from this study suggest that a cutoff score of 11, lower than that
      indicated in the literature, improves the diagnostic accuracy of the EAT-26 in a
      high-risk setting regarding sensibility level (68.1%) and leading to a reduction
      of the false negative rate (31.9%).

PMID- 16432541
TI  - Fat-specific transgenic expression of resistin in the spontaneously hypertensive
      rat impairs fatty acid re-esterification.
AB  - OBJECTIVE: To investigate the mechanism by which fat-specific transgenic
      expression of resistin affects fatty acid metabolism in the spontaneously
      hypertensive rat (SHR). DESIGN: Basal- and adrenaline-stimulated lipolysis, basal
      and insulin-stimulated lipogenesis as well as the site (glycerol versus acyl
      moiety) of glucose incorporated into triglycerides were determined in adipose
      tissue isolated from SHR-Resistin transgenic and SHR control rats. RESULTS: A
      moderate expression of transgenic resistin in adipose tissue was associated with
      significant increase in the FFA/glycerol ratio during adrenaline-stimulated
      lipolysis in the SHR-Resistin transgenic rats (3.27+/-0.26) compared to SHR
      controls (2.11+/-0.10, P=0.0005). Transgenic SHR also exhibited a significant
      decrease in FFA re-esterification in adipose tissue (approximately by 23%).
      CONCLUSION: These findings raise the possibility that the prodiabetic effects of
      transgenic resistin may be partly mediated by increased FFA release from adipose
      tissue due to impaired FFA re-esterification in adipocytes.

PMID- 16432542
TI  - Associations between daily food intake and excess adiposity in Irish adults:
      towards the development of food-based dietary guidelines for reducing the
      prevalence of overweight and obesity.
AB  - BACKGROUND: The prevalence of obesity has nearly doubled in Ireland since 1990
      and over half of the population has a large waist circumference (WC). No food
      based, dietary guidelines exist in Ireland for a reduction in the prevalence of
      body fat or obesity. OBJECTIVE: To examine the association between daily food
      intake and categories of body mass index and WC for the development of dietary
      guidelines to combat obesity. DESIGN: Cross-sectional study of a random
      representative sample of 1379 adults aged 18-64 years from Northern Ireland and
      the Republic of Ireland. MEASUREMENTS: Weight, height and WC were measured
      according to standard procedures. Diet was assessed using a 7-day food diary from
      which 28 food groups were generated and entered into logistic regression
      analysis. RESULTS: Higher mean daily consumption of most of the 28 food groups
      was associated with an increased likelihood of being classified as obese or at
      waist action level 2, compared to normal weight and normal WC. The strongest
      associations were found for savoury snacks, butter and full fat spreads. Contrary
      to popular opinion, not one individual food group but rather a combination of
      many foods was associated with excess adiposity. CONCLUSIONS: Body mass index and
      WC in adults are strongly influenced by the amount of food consumed. Public
      health policies for a reduction in body fat and obesity may be more effective if
      the emphasis is placed on a reduction of food and beverages consumed as opposed
      to the traditional dietary recommendations for macronutrients.

PMID- 16432543
TI  - The Gln223Arg polymorphism in the leptin receptor is associated with familial
      combined hyperlipidemia.
AB  - OBJECTIVE: Familial combined hyperlipidemia (FCH) is characterized by elevated
      levels of total cholesterol (TC), triglycerides (TG) and apolipoprotein B (apo B)
      and is associated with premature cardiovascular disease (CVD). Other features of
      FCH are obesity and insulin resistance. Serum leptin levels have also been
      associated with obesity, insulin resistance and atherosclerosis. Leptin exerts
      its effect through the leptin receptor (LEPR). The aim of this study is to
      determine whether the Gln223Arg polymorphism in the LEPR gene contributes to FCH
      and its associated phenotypes. METHODS: The study population consists of 37
      families, comprising 644 subjects, of whom 158 subjects were diagnosed as FCH.
      The FCH diagnosis was based on plasma TC and TG levels, adjusted for age and
      gender, and absolute apo B levels, according to our recently published nomogram.
      The Gln223Arg polymorphism was studied by restriction fragment length
      polymorphism-PCR. RESULTS: Carriers of one or two Arg alleles had an increased
      risk of FCH, compared to subjects homozygous for the Gln allele (OR=1.6 [95% CI
      1.0-2.4]). A difference in high-density lipoprotein cholesterol (HDL-c) levels
      was present between carriers and non-carriers of an Arg allele, 1.21 vs 1.28
      mmol/l, respectively (P=0.04), but no differences in obesity, insulin resistance
      and other lipid parameters were found. CONCLUSION: The Gln223Arg polymorphism in
      the LEPR gene is associated with FCH, which is supported by a significant
      association between HDL-c levels and the LEPR gene.

PMID- 16432544
TI  - Effect of obesity on P-wave dispersion and QT dispersion in women.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of obesity on
      dispersion of P-wave duration and QTc interval in obese women. METHODS: Forty-two
      obese women (Body mass index (BMI)=40+/-3 kg/m(2), mean age 45+/-9 years) and
      compared age-matched (BMI=22+/-1 kg/m(2), mean age 41+/-6 years) twenty-five non
      obese women were included in our study. Maximum and minimum P-wave duration, P
      wave dispersion (difference between the maximum and the minimum P-wave duration),
      maximum and minimum QTc interval, and QTc dispersion (the difference between the
      maximum and the minimum QTc interval) were measured from 12-lead ECG. ECG's were
      transferred to a personal computer via a scanner and then used for magnification
      of 400 times by Adobe Photoshop software. RESULTS: There was significant
      difference in BMI (40+/-3 vs 22+/-1 kg/m(2), P<0.001, respectively) between obese
      and non-obese women. Obese women had higher Max. P-wave duration (116+/-11 vs
      94+/-14 ms, P<0.001), P-wave dispersion (51+/-15 vs 26+/-11 ms, P<0.001), Max.
      QTc interval (449+/-38 vs 419+/-30 ms, P<0.001) and QTc dispersion (57+/-23 vs
      38+/-15 ms, P<0.001) compared to non-obese women. A significant correlation was
      found between BMI and Max. P-wave duration (r=0.584, P<0.001), P-wave dispersion
      (r=0.621, P<0.001), Max. QTc interval (r=0.410, P<0.001), and QTc dispersion
      (r=0.429, P<0.001). In the linear regression analysis, compared to co-morbidity
      factors such as age, hypertension, diabetes mellitus and smoking, there was
      significant association between only BMI and electrocardiographic values (P-wave
      and QTc dispersion). CONCLUSION: We concluded that obesity caused significant
      increase in P-wave and QTc dispersion. Therefore, obese women may not only be
      under the risk of ventricular arrhythmias, but also they may under the risk of
      atrial arrhythmias.

PMID- 16432545
TI  - Prediction of fat-free mass by bioimpedance analysis in migrant Asian Indian men
      and women: a cross validation study.
AB  - BACKGROUND: Bioimpedance analysis (BIA) is a fast and convenient field technique
      for estimation of total body fat-free mass (FFM). However, bioimpedance-based
      prediction equations have been developed in predominantly white populations and
      little information is available on their usefulness in Asian Indian populations.
      OBJECTIVE: To develop a prediction equation for FFM based on BIA measurements
      applicable to a migrant population of Asian Indians and to investigate the
      predictive accuracy of published BIA-based equations in this ethnic group.
      DESIGN: FFM was measured by dual-energy X-ray absorptiometry in 211 healthy
      adults (110 men, 101 women; age ranges 19-74 year) of Asian Indian ethnicity and
      used as the reference measure to develop prediction equations based on single
      frequency BIA measurements of resistance and reactance. A cross-validation
      technique was applied. Predictive accuracy of published BIA-based equations was
      assessed in this sample. RESULTS: Sex-specific equations developed in the entire
      group included height2/resistance and body weight as predictors (R2=0.84 and 0.70
      and standard errors of estimate of 2.8 and 2.0 kg for males and females,
      respectively; CV: 6%). Of published equations examined, one predicted FFM
      satisfactorily in men with nonsignificant bias and may be applicable to Asian
      Indian populations. None of the published equations tested performed
      satisfactorily in women. CONCLUSIONS: Bioimpedance-based equations for predicting
      FFM developed specifically in Asian Indians are recommended for field studies
      designed to measure body composition of this ethnic group.

PMID- 16432546
TI  - A study of central fatness using waist-to-height ratios in UK children and
      adolescents over two decades supports the simple message--'keep your waist
      circumference to less than half your height'.
AB  - OBJECTIVE: To examine the influence of age and gender on the waist:height ratio
      (WHTR) in children and to compare changes over time in WHTR, a measure of central
      fatness in British children. DESIGN: Representative cross-sectional surveys in
      1977, 1987 and 1997. SETTING: Great Britain and Northern Ireland. PARTICIPANTS:
      Survey 1: children aged 5-16 years measured in 1977 (boys) and 1987 (girls) (BSI,
      n=8135) and Survey 2: children aged 11-16 measured in 1997 (NDNS, n=773). OUTCOME
      MEASURES: From Survey 1, waist: height ratio related to age and sex and the
      proportion of children with a WHTR greater than 0.500 (a boundary value suggested
      for adults). From Survey 2, comparison of WHTR in children with that from Survey
      1 and the actual proportion of children with a WHTR greater than 0.500 compared
      with the expected proportion using the survey 1 as reference. RESULTS: WHTR
      decreased with age (P<0.01 for trend), with the mean WHTR being significantly
      lower in girls (P<0.01). WHTR was significantly greater in children in Survey 2
      compared with those measured 10 and 20 years earlier in Survey 1 (P<0.0001). The
      proportion of children where WHTR exceeded the 0.500 boundary value in Survey 2
      was 17% of boys and 11.7% of girls (against 5.0 and 1.5%, respectively, in Survey
      1, P<0.0001). The increase in WHTR in boys exceeded that in girls. CONCLUSIONS:
      Values of WHTR during the past 10-20 years have increased greatly showing that
      central fatness in children has risen dramatically. WHTR is more closely linked
      to childhood morbidity than body mass index (BMI) and we suggest it should be
      used as an additional or alternative measure to BMI in children as well as
      adults. A simple public health message that is the same for adults and children
      of both sexes and all ages could be stated as 'keep your waist circumference to
      less than half your height'.

PMID- 16432547
TI  - Weight loss in overweight patients maintained on atypical antipsychotic agents.
AB  - BACKGROUND: Weight gain and associated medical morbidity offset the reduction of
      extrapyramidal side effects associated with atypical antipsychotics. Efforts to
      control weight in antipsychotic-treated patients have yielded limited success.
      METHODS: We studied the impact of an intensive 24-week program of diet, exercise,
      and counseling in 17 chronically psychotic patients (10 women, seven men) who
      entered at high average body weight (105.0+/-18.4 kg) and body mass index (BMI)
      (36.6+/-4.6 kg/m(2)). A total of 12 subjects who completed the initial 24 weeks
      elected to participate in an additional 24-week, less intensive extension phase.
      RESULTS: By 24 weeks, weight-loss/patient averaged 6.0 kg (5.7%) and BMI
      decreased to 34.5 (by 5.7%). Blood pressure decreased from 130/83 to 116/74 (11%
      improvement), pulse fell slightly, and serum cholesterol and triglyceride
      concentrations changed nonsignificantly. With less intensive management for
      another 24 weeks, subjects regained minimal weight (0.43 kg). CONCLUSIONS: These
      findings add to the emerging view that weight gain is a major health problem
      associated with modern antipsychotic drugs and that labor-intensive weight
      control efforts in patients requiring antipsychotic treatment yield clinically
      promising benefits. Improved treatments without weight-gain risk are needed.

PMID- 16432548
TI  - Validity of body mass index and waist circumference in the classification of
      obesity as compared to percent body fat in Chinese middle-aged women.
AB  - OBJECTIVE: To evaluate the validity of currently recommended obesity cutoffs of
      body mass index (BMI, in kg/m(2)) and waist circumference (WC, in cm) for Asians
      by the WHO/IASO/IOTF and for Chinese by the Working Group on Obesity in China
      (WGOC) using the percentage body fat (%BF)-obesity criteria. DESIGN: A cross
      sectional study. SUBJECTS: A total of 1122 community-based Hong Kong Chinese
      women aged between 41 and 63 years. MEASUREMENTS: Total %BF and percent truncal
      fat (%TF) were measured using dual-energy X-ray absorptiometry. Anthropometric
      indices were measured using standard methods. RESULTS: Regression analyses showed
      that the BMI cutoffs of 23, 24, 25, and 28 kg/m(2) corresponded to the %BF of
      34.8, 35.9, 36.9 and 39.5%, and the 80 cm WC corresponded to 34% TF,
      respectively. Compared with the %BF obesity cutoff (>/=40%), the WHO/IASO/IOTF
      BMI-obesity criterion (>/=25) shows a good sensitivity (75%) and specificity
      (71%); and the WGOC criterion (BMI>/=28) had a low sensitivity (41%) but an
      excellent specificity (93%), respectively. Corresponding to the BMI cutoffs of
      23, 24, 25 and 28 kg/m(2), the %BF cutoffs associated with peak kappa statistic
      were 33, 34, 35 and 40%, and the relevant %TF linked with 80 cm WC was 33%,
      respectively. CONCLUSION: BMI and WC have a good accuracy in the prediction of
      obesity. Our findings suggest that the WGOC BMI cutoffs are appropriate, but 80
      cm of WC is a very rigorous cutoff for this population when using the criteria of
      34 and 40% of body fat or truncal fat for overweight and obesity.

PMID- 16432549
TI  - The influence of a 3-month weight reduction therapy with Orlistat on serum
      vitamin B12 and folic acid concentration in obese women.
AB  - OBJECTIVE: Serum folic acid, but not the vitamin B(12) concentration, was found
      to be significantly lower in obese subjects than in the control ones. DESIGN: The
      aim of this study was to examine the levels of serum vitamin B(12) and folic acid
      in obese women before and after weight reduction therapy with Orlistat in
      comparison to healthy controls with normal body weight. SUBJECTS: Twenty obese
      women participated in a 3-month weight reduction therapy. The control group
      consisted of 20 healthy women. MEASUREMENTS: Body weight and height were measured
      and BMI was calculated. Body composition was analyzed with the impedance method
      using a Bodystat analyzer. In all patients before and after 3-month weight
      reduction therapy, serum concentrations of folic acid and vitamin B(12) were
      assessed. RESULTS: In obese women, serum concentrations of folic acid and vitamin
      B(12) did not change significantly after 3-month weight reduction therapy with
      Orlistat.

PMID- 16432550
TI  - The criterion validity of a last 7-day physical activity questionnaire (SAPAQ)
      for use in adolescents with a wide variation in body fat: the Stockholm Weight
      Development Study.
AB  - OBJECTIVE: The aim of the present study was to assess the criterion validity of a
      newly developed self-reported last 7-day physical activity questionnaire (SAPAQ)
      for use in Swedish adolescents with a wide variation in body fatness.
      MEASUREMENTS: We compared the self-reported total number of MET-minutes with
      objectively assessed variables of physical activity obtained by accelerometry in
      49 (18 male, 31 female subjects) 17-year-old adolescents. RESULTS: Self-reported
      physical activity was significantly and inversely related to time spent sedentary
      (r=-0.45; P<0.001) and significantly and positively associated with time spent in
      physical activity (r=0.51; P<0.001) and the total amount of physical activity
      (r=0.49; P<0.001). Gender and body fat did not affect the associations between
      self-reported and objectively assessed physical activity. CONCLUSION: Our results
      indicate that the newly developed questionnaire is a valid method for ranking
      individuals in terms of the total amount of physical activity in Swedish
      adolescents.

PMID- 16432552
TI  - Mechanisms of cellular signal transduction.

PMID- 16432551
TI  - Plant stanol ascorbate esters reduce body weight gain through decreased energy
      absorption in hamsters.
AB  - OBJECTIVE: The objective of this study was to determine the effects of disodium
      ascorbyl phytostanyl phosphate (DAPP), a novel hydrophilic phytostanol analogue,
      on energy homeostasis, including body weight and intestinal energy absorption,
      and plasma triglyceride concentrations, in hamsters. METHODS: Male Golden Syrian
      hamsters (n = 50) were fed for 5 weeks with experimental diets varying in
      cholesterol and phytostanol content. Diets included (i) non-cholesterol
      (semipurified diet without added cholesterol), (ii) cholesterol-control
      (semipurified diet with 0.25% cholesterol), (iii) stanol (cholesterol-control
      with 1% free phytostanols), (iv) DAPP 0.7% (cholesterol-control with 0.71% DAPP)
      or (v) DAPP 1.4% (cholesterol-control with 1.43% DAPP). Fecal samples were
      collected continuously for 3 days on week 3, and fecal energy output was measured
      by bomb calorimetry. RESULTS: Hamsters fed 1.4% DAPP gained less (P<0.05) weight
      than hamsters fed non-cholesterol and stanol diets. Diets had no effect on total
      food consumption or gross energy intake after 5 weeks, but lower (P<0.05) weekly
      food consumptions in hamsters fed 1.4% DAPP were observed at weeks 1 and 2 of the
      experiment in comparison to animals fed the non-cholesterol diet. In comparison
      to non-cholesterol and cholesterol-control diets, DAPP 1.4% increased (P<0.01)
      fecal energy output by 47 and 46%, respectively. In hamsters supplemented with
      1.4% DAPP, plasma triglyceride concentrations were 45% lower (P<0.05) than in
      cholesterol-control fed hamsters. Furthermore, plasma triglyceride levels in the
      DAPP 1.4% group was 49% lower (P<0.01) than in the stanol group, despite the fact
      that both diets contained equivalent amounts of phytostanols. The lower
      concentration of DAPP (0.7%) also reduced plasma triglycerides (P<0.05) compared
      with the stanol diet. CONCLUSION: Stanol-ascorbate decreases body weight gain in
      hamsters, likely due to lower energy absorption at the intestinal level. In
      addition to its previously observed powerful cholesterol-lowering effect, DAPP
      has a hypotriglyceridemic function in hamsters.

PMID- 16432553
TI  - The future of virtual colonography. Interview by Paul C Adams.

PMID- 16432554
TI  - Gallstone pancreatitis--who really needs an ERCP?

PMID- 16432555
TI  - Prion diseases and the gastrointestinal tract.
AB  - The gastrointestinal (GI) tract plays a central role in the pathogenesis of
      transmissible spongiform encephalopathies. These are human and animal diseases
      that include bovine spongiform encephalopathy, scrapie and Creutzfeldt-Jakob
      disease. They are uniformly fatal neurological diseases, which are characterized
      by ataxia and vacuolation in the central nervous system. Although they are known
      to be caused by the conversion of normal cellular prion protein to its infectious
      conformational isoform (PrPsc) the process by which this isoform is propagated
      and transported to the brain remains poorly understood. M cells, dendritic cells
      and possibly enteroendocrine cells are important in the movement of infectious
      prions across the GI epithelium. From there, PrPsc propagation requires B
      lymphocytes, dendritic cells and follicular dendritic cells of Peyer's patches.
      The early accumulation of the disease-causing agent in the plexuses of the
      enteric nervous system supports the contention that the autonomic nervous system
      is important in disease transmission. This is further supported by the presence
      of PrPsc in the ganglia of the parasympathetic and sympathetic nerves that
      innervate the GI tract. Additionally, the lymphoreticular system has been
      implicated as the route of transmission from the gut to the brain. Although
      normal cellular prion protein is found in the enteric nervous system, its role
      has not been characterized. Further research is required to understand how the
      cellular components of the gut wall interact to propagate and transmit infectious
      prions to develop potential therapies that may prevent the progression of
      transmissible spongiform encephalopathies.

PMID- 16432557
TI  - Analytical and biological variables influencing quantitative hepatitis C virus
      (HCV) measurement in HIV-HCV coinfection.
AB  - The present review considers issues pertaining to the precision and variability
      of quantitative hepatitis C virus (HCV) measurement in general, outlines the
      characteristics of HCV RNA in HIV-HCV coinfection and evaluates those factors
      which may affect this measure. The clinical relevance of accurate HCV measurement
      in HIV-HCV coinfection is discussed.

PMID- 16432556
TI  - Acute fatty liver of pregnancy.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication
      that occurs in the third trimester or early postpartum period. Although the exact
      pathogenesis is unknown, this disease has been linked to an abnormality in fetal
      fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because
      it shares features with other common conditions such as pre-eclampsia, viral
      hepatitis and cholestasis of pregnancy. However, a careful history and physical
      examination, in conjunction with compatible laboratory and imaging results, are
      often sufficient to make the diagnosis, and liver biopsy is rarely indicated.
      Supportive care and expeditious delivery are essential to optimal maternal-fetal
      outcomes and remain as the mainstay treatment for AFLP.

PMID- 16432558
TI  - Esophageal intramural pseudodiverticulosis with food impaction.
AB  - Esophageal intramural pseudodiverticulosis is a rare condition of unknown
      etiology originally described in 1960. It is characterized by multiple, flask
      shaped outpouchings of pinhead size in the wall of the esophagus. Very small
      outpouchings on endoscopy and tiny collections of barium outside of the esophagus
      wall on esophagography are typical diagnostic findings. During the era of
      widespread endoscopic and radiological evaluation of esophageal disorders,
      approximately 200 cases were published in the literature. A 52-year-old man with
      esophageal intramural pseudodiverticulosis with food impaction is reported. The
      patient's symptoms of dysphagia resolved with endoscopic dilations and proton
      pump inhibitor therapy.

PMID- 16432559
TI  - Duodenal hematoma following endoscopic duodenal biopsy: a case report and review
      of the existing literature.
AB  - Duodenal hematoma is a rare complication of endoscopic duodenal biopsy that
      occurs mainly in children or adults with impaired coagulation. The clinical
      presentation consists of signs of intestinal obstruction, and pancreatitis and
      direct hyperbilirubinemia are possible complications caused by ampullary
      obstruction. A case of a six-year-old girl who presented with a duodenal hematoma
      and acute pancreatitis after having an endoscopic duodenal biopsy is reported. A
      review of the literature and data from all similar cases reported so far are
      briefly presented and discussed.

PMID- 16432560
TI  - Preparation of layered double hydroxides and their applications as additives in
      polymers, as precursors to magnetic materials and in biology and medicine.
AB  - In recent years layered double hydroxides (LDHs), also known as hydrotalcite-like
      materials, have attracted considerable interest from both industry and academia.
      In this article, we discuss methods of preparing LDHs with an emphasis on the way
      in which particle size and morphology can be controlled with regard to specific
      target applications; scale-up of one such preparation procedure is also
      described. In addition, we review selected applications of LDHs developed by our
      own and other laboratories.

PMID- 16432561
TI  - Poly-N-methylated alpha-peptides: synthesis and X-ray structure determination of
      beta-strand forming foldamers.
AB  - The first high resolution X-ray structure determination of poly-N-methylated
      alpha-peptides, a class of peptides widely used in biomedical research, is
      described; it shows that these molecules adopt a beta-strand conformation.

PMID- 16432562
TI  - Formation of highly ordered porphyrin adlayers induced by electrochemical
      potential modulation.
AB  - Molecular self-assembly of porphyrin derivatives formed with intermolecular
      hydrogen bonding on the surface of Au(111) electrode in acidic solution can be
      controlled by varying the number of peripheral carboxy groups and the applied
      electrochemical potential.

PMID- 16432563
TI  - Template-guided organization of chromonic liquid crystals into micropatterned
      anisotropic organic solids.
AB  - We have developed an approach to generate micropatterns of anisotropic organic
      materials which exploits the self-organization, driven by pi-stacking and
      hydrophobic interactions, of an ionic perylenebis(dicarboximide) in aqueous
      solutions.

PMID- 16432564
TI  - Anion-pi interaction augments halide binding in solution.
AB  - 1H NMR spectroscopic data and complementary theoretical predictions suggest that
      a designed receptor exhibits the anion-pi interaction in solution.

PMID- 16432565
TI  - Normal hydrocarbons tumble rapidly in a deep, water-soluble cavitand.
AB  - A deep, water-soluble cavitand extracts n-alkanes and other water-insoluble
      species into its cavity via hydrophobic forces: alkanes bind in a helical manner,
      and tumble rapidly on the NMR timescale inside the binding pocket.

PMID- 16432566
TI  - Constructing 2D porous material based on the assembly of large organic ions: p
      sulfonatocalix[8]arene and tetraphenylphosphonium ions.
AB  - In the presence of tetraphenylphosphonium and aquated ytterbium(III) ions,
      conformationally flexible p-sulfonato-calix[8]arene forms an extended structure
      with two dimensional porosity involving the assembly of phosphonium cations and
      'molecular capsules' comprised of two calixarenes shrouding three phosphonium
      cations.

PMID- 16432567
TI  - Light harvesting tetrafullerene nanoarray for organic solar cells.
AB  - A light absorbing pi-conjugated oligomer-tetrafullerene nanoarray has been
      synthesized and its photophysical study reveals the presence of an intramolecular
      energy transfer. A phototovoltaic device fabricated from this nanoarray and
      poly(3-hexylthiophene) shows an external quantum efficiency of 15% at 500 nm.

PMID- 16432569
TI  - Iron hydrogenase active site mimic holding a proton and a hydride.
AB  - The first model of the iron hydrogenase active site has been prepared which
      concomitantly carries a proton and a hydride; the title species was characterized
      by IR and NMR spectroscopy and is reduced at more positive potential than any
      other mimic of this kind.

PMID- 16432568
TI  - Cyclodextrin-based isolation of Ostwald's metastable polymorphs occurring during
      crystallization.
AB  - We describe a novel approach for the selective isolation of Ostwald's
      intermediate metastable polymorphs occurring during an early stage of
      crystallization, by utilizing the inclusion complex formed with a cyclic
      oligosaccharide derivative, 2,6-di-O-methyl-beta-cyclodextrin.

PMID- 16432570
TI  - Synthesis and disruption of a tetrametallic zinc hydrazide.
AB  - Treatment of 1,1'-dimethylhydrazine, Me2NNH2 with excess diethylzinc affords a
      novel tetrametallic Zn4N8 cage complex, which on further reaction with tBuLi
      forms a lithium-bridged chain of Zn4N7 cages.

PMID- 16432571
TI  - Unprecedented 1,4-stannatropy: effective generation of azomethine ylides as
      nitrile ylide equivalents from N-(stannylmethyl)thioamides.
AB  - Generation and cycloaddition of less- or non-stabilized azomethine ylides, or
      nitrile ylide equivalents, via unprecedented 1,4-stannatropy of N
      (tributylstannylmethyl)thioamides were achieved. The reactions with
      dipolarophiles, such as electron-deficient alkenes and alkynes, afforded
      corresponding pyrrolidine and pyrrole derivatives effectively.

PMID- 16432572
TI  - Probing the influence of cis-trans isomers on model lipid membrane fluidity using
      cis-parinaric acid and a stop-flow technique.
AB  - Stop-flow experiments exploiting the fluorescence of cis-parinaric acid in
      monounsaturated lipid vesicles allow the model membrane behaviour, notably the
      membrane fluidity, to be correlated to the cis:trans lipid ratios.

PMID- 16432573
TI  - 68Zn isotope exchange experiments reveal an unusual kinetic lability of the metal
      ions in the di-zinc form of IMP-1 metallo-beta-lactamase.
AB  - The apparently paradoxical behaviour of facile exchange (kinetic lability) of
      tightly bound (thermodynamic stability) zinc ions in the enzyme IMP-1 metallo
      beta-lactamase with Zn-68 and cadmium ions, as indicated by in-torch vaporization
      inductively-coupled plasma mass spectrometry (ITV-ICP-MS) and electrospray
      ionization mass spectrometry (ESI-MS), is consistent with the involvement of a
      third metal ion in promoting Lewis acid/base type exchange processes.

PMID- 16432574
TI  - Interface engineering for solid-state dye-sensitised nanocrystalline solar cells:
      the use of an organic redox cascade.
AB  - We demonstrate the formation of a charge transfer cascade at a nanostructured
      TiO2/dye/polymer/molecular hole transport multilayer interface. Charge
      recombination dynamics at this interface are shown to be retarded when the
      ionisation potential of the polymer layer exceeds that of the molecular hole
      transport layer.

PMID- 16432575
TI  - Surface self-assembly of the cyanuric acid-melamine hydrogen bonded network.
AB  - A hydrogen-bonded bimolecular network formed between cyanuric acid (CA) and
      melamine (M), CA x M, has been prepared by a surface-based self-assembly process;
      the monolayer CA x M network is prepared under ultra-high vacuum conditions
      either by sequential deposition of CA followed by M, or through simultaneous
      deposition of the component molecular species.

PMID- 16432577
TI  - Highly reversible lithium metal secondary battery using a room temperature ionic
      liquid/lithium salt mixture and a surface-coated cathode active material.
AB  - For the purpose of realizing high-voltage, high-capacity, long-life and safe
      rechargeable batteries, a lithium secondary battery that uses high-voltage stable
      ZrO2-coated LiCoO2 cathode powder and a nonvolatile high-safety room temperature
      ionic liquid was fabricated.

PMID- 16432576
TI  - One pot synthesis of selenocysteine containing peptoid libraries by Ugi
      multicomponent reactions in water.
AB  - Selenocysteine containing peptoids and peptide-peptoid conjugates were
      synthesized by combinatorial Ugi-MCRs (multicomponent reactions) in water: for
      the first time, an acetal (selenoacetal 2a) was used in Ugi-MCR to furnish
      selenocysteine peptoids in one step as model compounds for selenocysteine
      peptides and proteins.

PMID- 16432578
TI  - Rapid formation of amides via carbonylative coupling reactions using a
      microfluidic device.
AB  - Carbonylative cross-coupling reactions of arylhalides to form secondary amides
      were rapidly carried out on a glass-fabricated microchip--the first time a
      microstructured device has been used to perform a gas-liquid carbonylation
      reaction.

PMID- 16432580
TI  - Misassigned C-H...Cu agostic interaction in a copper(II) ephedrine derivative is
      actually a weak, multicentred hydrogen bond.
AB  - Agostic interactions and weak hydrogen bonds to metal acceptors, M, are
      chemically and geometrically distinct, and this distinction must be maintained in
      the classification of new C-H...M interactions.

PMID- 16432579
TI  - Mechanistic studies of an unusual epoxide-forming elimination of a beta
      hydroxyalkyl rhodium porphyrin.
AB  - A new and remarkably facile sp3-C-O bond forming reaction of beta-hydroxyalkyl Rh
      porphyrins to form epoxides has been discovered and its mechanism investigated.

PMID- 16432582
TI  - On the role of alkylcobalamins in the vitamin B12-catalyzed reductive
      dehalogenation of perchloroethylene and trichloroethylene.
AB  - Theoretical studies are presented on the structures and reactivity of chlorinated
      ethylcobalamins, potential intermediates in the vitamin B12-catalyzed reductive
      dehalogenation of the environmental pollutants perchloroethylene and
      trichloroethylene; the results suggest an alternative mechanism of catalysis.

PMID- 16432581
TI  - Synthon evolution and unit cell evolution during crystallisation. A study of
      symmetry-independent molecules (Z' > 1) in crystals of some hydroxy compounds.
AB  - A kinetically favoured crystal, with many molecules in the asymmetric unit, may
      be a fossil relic of the crystal nucleus of a more stable polymorph.

PMID- 16432583
TI  - Remarkable oxidizing ability of triplet excited states of tetrazines produced by
      photosensitization with Ru(bpy)3(2+).
AB  - An efficient energy transfer from Ru(bpy)3(2+)* (bpy = 2,2'-bipyridine, * denotes
      the excited state) to tetrazines occurs to yield the triplet excited states of
      tetrazines, which have much longer lifetimes and higher oxidizing ability as
      compared with those of Ru(bpy)3(2+)*.

PMID- 16432584
TI  - Conversion of 2-(4-carboxyphenyl)-6-nitrobenzothiazole to 4-(6-amino-5
      hydroxybenzothiazol-2-yl)benzoic acid by a recombinant E. coli strain.
AB  - E. coli C43(DE3)pNbzAHabA, expressing nitroreductase and mutase enzymes, converts
      2-(4-carboxyphenyl)-6-nitrobenzothiazole to 4-(6-amino-5-hydroxybenzothiazol-2
      yl)benzoic acid.

PMID- 16432586
TI  - Molecular basis of breast cancer.
AB  - Breast cancer is the most frequent cancer in women and represents the second
      leading cause of cancer death among women after lung cancer. A common phenotypic
      abnormality of breast cancer cells is dysregulation of cell cycle control. The
      transformation of normal cell to a cancer cell appears to depend on mutation in
      genes that normally control cell cycle progression, thus leading to loss of the
      regulatory cell growth. We summarize here the molecular regulation of mammary
      carcinoma with regards to the most prominent oncogenes and tumor suppressor genes
      and their outcome in terms of cellular prognosis, and tumor development.

PMID- 16432587
TI  - The effect of vitamin E, L-arginine, N-nitro L-arginine methyl ester and
      forskolin on endocrine and metabolic changes of rats exposed to acute cold
      stress.
AB  - OBJECTIVE: It is a well documented fact that under stress conditions the
      hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic nervous system
      (SNS) are stimulated. This results in a series of neural and endocrine
      adaptations known as the stress response. The current study assessed the effects
      of acute cold stress on adrenomedullin (ADM) levels in plasma and peripheral
      tissues (kidneys and heart) of rats, as well as on blood glucose, cholesterol,
      triglycerides (TG), total proteins both before and after intraperitoneal
      administration of each of the following: vitamin-E, L-arginine, forskolin and L
      NAME. METHODS: The current study was conducted in the Department of Physiology,
      Faculty of Medicine, King Saud University, Saudi Arabia, between September 2003
      and March 2004. We observed 6 groups of Wistar rats for their plasma ADM, tissue
      plasminogen activator (t-PA), total protein, glucose and cholesterol levels.
      Following exposure to cold stress (-10 degree C for 3 hours). RESULTS: Acute cold
      stress produced a significant increase in ADM levels in plasma, heart and kidney
      tissues of rats. Furthermore, acute cold stress produced a reduction in
      cholesterol and plasma protein levels. On the other hand, acute cold stress
      caused an increase in TG, glucose plasma levels and tissue plasminogen activator
      (t-PA). We found hormonal and metabolic changes caused by cold exposure to be
      decreased or even prevented after vitamin E treatment or after changing nitric
      oxide (NO) level by L-arginine or L-NAME treatment. CONCLUSION: The results
      suggest a regulatory or protective role for ADM in counteracting HPA activation
      following a variety of physiological and psychological stressors. Oxidative
      stress or changes in intracellular signals as NO, cyclic-AMP may play a role in
      explaining some of the metabolic and hormonal changes occurring during acute cold
      stress.

PMID- 16432588
TI  - Ramadan fasting induces modifications of certain serum components in obese women
      with type 2 diabetes.
AB  - OBJECTIVE: To examine the effect of fasting during Ramadan on certain serum
      components such as fasting serum glucose (FSG), glycated hemoglobin (HbA1c),
      total cholesterol (TC), triglycerides (TGs), high density lipoproteins (HDL-C),
      and low density lipoproteins (LDL-C) parameters in obese women patients with type
      2 diabetes. METHODS: We conducted the study in Petit-Vichy Diabetology Center,
      Sidi-Bel-Abbes, Algeria from October 2003 to March 2004, on 60 obese outpatient
      women (BMI = 35.41 +/- 3.64 kg/m2), aged 51 +/- 10 years, who had diabetes for 5
      +/- 2.5 years. The patients followed no specific diet, on medications, and
      presenting no degenerative complications. We carried out the study over 3
      periods: before (pre-fasting), during (fasting), and after Ramadan month (post
      fasting). RESULTS: Comparing Ramadan (fasting period) with non-Ramadan days (pre-
      and post-fasting periods), we observed significant decreases in FSG (16.72%,
      p<0.001), in HbA1c (11.3%, p<0.005), and in HDL-C (26.81%, p<0.001) rates, while
      TC (13.85%, p<0.001), TGs (16.9%, p<0.003), and the LDL-C (22.39%, p<0.0001)
      levels increased significantly. CONCLUSION: These findings show a beneficial
      effect of fasting during Ramadan on glucose homeostasis, however, we observed an
      unbalanced profile on lipids.

PMID- 16432589
TI  - Echocardiographic study of aortic root diameter in healthy children.
AB  - OBJECTIVE: Echocardiography is commonly used to measure the internal diameter of
      aortic root, which provides the evaluation of aortic root dilatation. Aortic root
      dilatation provide information concerning prognosis of aortic regurgitation and
      predisposition to aortic root dissection or rupture. The purpose of the study was
      to create normal values for aortic root diameters by using echocardiography in
      healthy children. METHODS: We obtained the aortic root diameters in 229 normal
      children, aged one day to 15 years by using M-mode echocardiography. We performed
      the echocardiograms from the Department of Pediatric Echocardiography Laboratory,
      Medical Faculty, Dicle University, Turkey. We divided the children into 6 groups
      according to their body surface area (BSA): 0.20-0.25 m2, 0.25-0.50 m2, 0.50-0.75
      m2, 0.75-1.0 m2, 1.0-1.25 m2, and 1.25-1.50 m2. We corrected the aortic root
      diameters for BSA. RESULTS: The aortic root diameters in children were 7.6 mm to
      24 mm with a mean value of 14.8 mm. The corrected aortic root diameter for BSA
      ranged from 10.7 to 40.6 mm/m2 with a mean value of 19.9 mm/m2. Aortic root
      diameters increased with age, weight and BSA. In contrast, aortic root
      diameter/BSA values were higher in younger children. CONCLUSION: The presented
      aortic root diameters according to the BSA will serve as reference data for
      echocardiographic evaluation of patients with various cardiac diseases.

PMID- 16432590
TI  - Evaluation of a new dot blot assay for confirmation of human immunodeficiency
      virus type 1 and 2 infections using recombinant p24, gp41, gp120 and gp36
      antigens.
AB  - OBJECTIVE: A sensitive and accurate dot blot assay using recombinant p24 (gag),
      gp41 and gp120 (env) proteins of HIV-1 and also recombinant gp36, the specific
      HIV-2 antigen was developed to confirm the presence of antibodies in sera
      reactive in screening enzyme-linked immunosorbent assays. METHODS: We collected
      sera from Iranian 125 confirmed HIV positive Iranian samples (seropositive group)
      from AIDS patients, asymptomatic HIV-infected subjects, HIV-infected intravenous
      drug users and also hemophilic infected subjects. The samples were obtained from
      the AIDS Specimen Bank, Pasture Institute, Iran during 2002 to 2003. We also
      obtained 180 samples (seronegative group) from healthy blood donors. Recombinant
      antigens were expressed in Escherichia coli. By use of highly purified antigens,
      the dot blot procedure was developed. Analysis of the results was accomplished by
      capturing the dot blot images. RESULTS: We established and interpreted the
      results using Centers for Disease Control criteria. We defined the positive test
      result as the presence of antibody against at least 2 different HIV gene
      products, one of which had to be an env gene product while a negative test result
      was defined as no antibodies against any of the HIV gene products and an
      indeterminate result was defined as antibodies reacting with only one HIV env
      gene product or against gag gene product only. CONCLUSION: The recombinant HIV
      dot blotting assay identified seropositive individuals with a high degree of
      accuracy; none of the HIV-seropositive subjects had a negative test result.
      Reactivity with these antigens, demonstrated 100% sensitivity and specificity in
      distinguishing seronegative from seropositive sera. The different sets of Western
      blot interpretative accepted criteria did not make a difference in interpretation
      of the seronegative and seropositive samples.

PMID- 16432591
TI  - Prevalence of extended-spectrum beta-lactamases among Enterobacteriaceae isolated
      from blood culture in a tertiary care hospital.
AB  - OBJECTIVE: To determine the prevalence of extended spectrum beta-lactamase among
      Enterobacteriaceae isolated from blood culture in a tertiary care hospital.
      METHODS: We carried out this study at the Armed Forces Hospital, Riyadh, Kingdom
      of Saudi Arabia during the period between January 2003-December 2004. We tested a
      total of 601 isolates of the family Enterobacteriaceae from blood culture for the
      prevalence of extended spectrum beta-lactamase (ESBL) production by the
      standardized disc diffusion method and confirmed by the ESBL E test strips.
      RESULTS: Ninety-five (15.8%) of the isolates were ESBL producers. Among these,
      48.4% were Klebsiella pneumoniae (K. pneumoniae) followed by 15.8% of both
      Escherichia coli (E. coli) and Enterobacter cloacae (Ent. cloacae). Other
      isolates produced ESBL in low numbers. CONCLUSION: Klebsiella pneumoniae produced
      ESBL in significant numbers. Extended spectrum beta-lactamase gram-negative
      bacilli present significant diagnostic and therapeutic challenges to the
      management of infections due to these organisms. Microbiology laboratories should
      start reporting ESBL producing Enterobacteriaceae organism due to their
      importance in respect to antibiotic therapy and infection control aspects.

PMID- 16432592
TI  - A study of bacterial isolates from corneal specimens and their antibiotic
      resistance profile.
AB  - OBJECTIVE: We aim to examine the spectrum of bacteria causing corneal infections
      and their antibiotic susceptibility patterns. This will serve as a guideline for
      empiric therapy of corneal infections. METHODS: We conducted the study over a
      period of 18 months from March 2001 through December 2002 in King Abdul-Aziz
      University Hospital, Riyadh, Kingdom of Saudi Arabia. Corneal specimens taken
      from 200 patients were inoculated directly onto different types of media. The
      isolates were identified and then tested against the appropriate topical or
      systemic antibiotics. RESULTS: Sixty-seven (33.5%) of the total specimens were
      culture positive and 133 (66.5%) were culture negative. Fourteen (7%) of these
      showed organisms in the Gram stained smears and correlated well with the culture
      reports. Of the 67 positive cultures, 53 (79.1%) were Gram-positive bacteria
      mostly coagulase-negative Staphylococci 29 (43.3%) followed by Streptococcus
      pneumoniae (S. pneumoniae) 13 (19.4%). Among Gram-negative bacteria 14 (20.9%),
      Pseudomonas aeruginosa (P. aeruginosa) 10 (14.9%) was the predominant isolate.
      All the isolates were sensitive to ofloxacin and the commonly used ocular
      antibiotics. CONCLUSION: All the isolated bacteria were sensitive to ofloxacin, a
      fluoroquinolone. Having marked potency for broad-spectrum activity against both
      Gram-positive and Gram-negative bacteria, make the fluoroquinolones especially
      the newer generations, a potential single drug therapy for corneal infections.

PMID- 16432593
TI  - Effect of cyclophosphamide on the course of Candida albicans infection in normal
      and vaccinated mice.
AB  - OBJECTIVE: To evaluate the immunomodulating effect of cyclophosphamide (Cy) on
      the course of Candida albicans (C. albicans). METHODS: We performed this study in
      the Shiraz Medical School, Shiraz, Iran during April to November 2003. Five
      groups of 10 mice (vaccinated group) were immunized by 5 equal injections of 2 x
      10(5), 2.5 x 10(5) and 3 x 10(5) of the organism intraperitoneally. Then, the
      group received Cy on day zero and was challenged with lethal doses of C. albicans
      (7.74 x 10(5) colony forming unit) on days zero, one, 3, 6 and 12 post-Cy
      injection. Another 5 equal groups of 10 mice (non-vaccinated group) received Cy
      on day zero and similar to vaccinated ones were challenged with lethal doses of
      the organism too. The control groups received just Cy on day zero and were
      sacrificed on days zero, one, 3, 6 and 12 days post-Cy injection. We performed
      the hemogram and the spleen and studied the renal tissues microscopically and
      macroscopically. RESULTS: In vaccinated group, we observed an increase in
      survival time and in spleen and renal weights were visible while in non
      vaccinated ones, a significant decrease was also observed on days one and 3 and
      an increased on days 6 and 12 post-Cy injection. We observed atrophy and necrosis
      in the spleen while inflammation and necrosis were also observed in the kidneys
      on days one and 3. We noticed a significant hyperplasia in the white pulp on days
      6 and 12 post-Cy injection. CONCLUSION: We conclude that hyperplasia in the white
      pulp of spleen and the increase in peripheral polymorphonuclears due to selective
      effects of Cy could effectively protect the animal against C. albicans infection.

PMID- 16432594
TI  - Ventilator-associated pneumonia in surgical emergency intensive care unit.
AB  - OBJECTIVE: To investigate the incidence, risk factors and the etiology of
      ventilator-associated pneumonia (VAP) in surgical emergency intensive care unit
      (ICU) patients. METHODS: We conducted this prospective cohort study in the
      surgical emergency ICU of Istanbul Medical Faculty between December 1999 and May
      2001. We included 100 mechanically ventilated patients in this study. We
      diagnosed VAP according to the current diagnostic criteria. We identified the
      etiology of VAP cases by both quantitative cultures of endotracheal aspiration
      and blood cultures. To analyze the predisposing factors for the development of
      VAP, we recorded the following variables: age, gender, acute physiology and
      chronic health evaluation (APACHE) II score, Glasgow coma scale (GCS), sequential
      organ failure assessment (SOFA) score, serum albumin level, duration of
      mechanical ventilation (MV) prior to the development of VAP, and underlying
      diseases. RESULTS: We determined the VAP incidence rate as 28%. We found the
      APACHE II score and the duration of MV to be statistically significant variables
      for the development of VAP. There were no significant differences regarding age,
      gender, GCS, SOFA score, albumin level, or underlying diseases for the
      development of VAP. The isolated bacteria among VAP cases were as follows:
      Staphylococcus aureus (n=12, 43%), Acinetobacter spp. (n=6, 21%), coagulase
      negative Staphylococci (n=4, 15%), Pseudomonas aeruginosa (n=3, 10.7%) and
      Klebsiella pneumoniae (n=3, 10.7%). CONCLUSION: Ventilator-associated pneumonia
      is a common infection, and certain interventions might affect the incidence of
      VAP. The ICU clinicians should be aware of the risk factors for VAP, which could
      prove useful in identifying patients at high risk for VAP, and modifying patient
      care to minimize the risk of VAP.

PMID- 16432595
TI  - Transfusion transmitted virus in screened United Arab Emirates blood donors.
AB  - OBJECTIVE: To investigate the rate of infection caused by Torque teno virus (TTV)
      in United Arab Emirates (UAEs) healthy population as a pilot study in detecting
      TTV DNA in 100 healthy blood donors. METHODS: We randomly choose a total of 100
      healthy blood donors who attended Zayed Military Hospital, Abu Dhabi, UAE from
      January 20 to May 30, 2005. We carried out a real-time polymerase chain reaction
      (PCR) test to detect TTV DNA. RESULTS: Real-time for TTV was positive in 75 (75%)
      donors. Eight (73%) non-UAE donors were TTV positive while 67 (75%) were UAEs.
      Among these donors, 72 (77%) were males and 3 (50%) were females. CONCLUSION: Our
      results demonstrated a high prevalence of TTV in UAE.

PMID- 16432597
TI  - Spectrum of general surgical problems in the developmentally disabled adults.
AB  - OBJECTIVE: This study highlights the spectrum of general surgical problems
      necessitating admission on intellectually disabled adult patients. Problems
      encountered in the management and the ways to overcome various difficulties are
      highlighted. METHODS: Prospective collection of data on 63 consecutive
      developmentally disabled adult patients admitted to the Department of General
      Surgery, Riyadh Medical Complex (RMC), Riyadh, Kingdom of Saudi Arabia for
      various indications from January 2000 through December 2004. Demographic details,
      clinical presentation, diagnostic modalities, associated physical and
      neurological disabilities, coexisting medical condition, treatment options,
      morbidity and mortality were analyzed. Various difficulties encountered during
      the management and mean to overcome these problems are addressed. RESULTS: Sixty
      three patients accounted for 71 admissions. Mean age was 26.7 years with a male
      preponderance (4.25:1). Fifty-four patients were admitted for various emergency
      conditions. History of pica could be obtained in 33% of the cases. Twenty-seven
      patients were admitted for acute abdomen. Volvulus of the colon (22.2%) and
      pseudo-obstruction (18.5%) were the most common causes of acute abdomen. Twenty
      one patients were admitted with upper gastrointestinal bleeding. Reflux
      esophagitis was the most common cause of bleeding (62%). Overall morbidity was
      41% for emergency admissions and 22% for elective surgery. Hospital mortality was
      21.4% for emergency surgery. There was no death in elective cases. CONCLUSION:
      Developmentally disabled patients comprise a special class of patients with
      peculiar management problems. The treating clinician should be aware of various
      unexpected conditions not found as frequently in the normal patient population.
      Apparent lack of pain does not exclude an acute emergency. Possible surgical
      condition should be suspected if there is vomiting, abdominal distension, fever,
      increased irritability of recent onset. Male gender and history of pica are added
      risk factors.

PMID- 16432596
TI  - A serological survey of measles, mumps and rubella immunity among school aged
      children in Western Saudi Arabia.
AB  - OBJECTIVE: To evaluate the adequacy of measles, mumps and rubella (MMR)
      vaccination among children and to assess risk of outbreak in Jeddah, Kingdom of
      Saudi Arabia (KSA). METHODS: We recruited a total of 527 children from schools
      located at different urban regions, and preschool children from those attending
      the well baby clinics in Jeddah, KSA. We tested for MMR viruses antibodies using
      ELISA technique. RESULTS: Approximately 99% of children received MMR vaccine.
      Overall seropositivity for measles antibodies was 71%, mumps 65% and rubella 90%,
      which were elevated in vaccinated versus non-vaccinated children (p<0.000). In
      vaccinated children, percentage of seropositivity for MMR was higher in public
      school children versus private (p<0.01) or those who did not attend school
      (p<0.01) and in Saudi versus non-Saudi children (p<0.000). In vaccinated
      children, percentage of seropositivity obtained according to age groups of 4-6
      years for measles was 73.7%, for mumps 66.7% and for rubella 91.7%. As for 7-11
      years age group, seropositivity for measles was 72.6%, for mumps 68.1% and for
      rubella 93%, while for the 12-14 years, seropositivity for measles was 66.4%,
      mumps 59.1% and for rubella 86.1%. The prevalence of seropositivity against the
      above-mentioned viruses decreased with progression of age. CONCLUSION: Measles,
      mumps and rubella mass vaccination program achieved high coverage rate among
      children, in Jeddah, KSA. However, there is still a high level of sera negative
      children among vaccinated ones for measles and mumps. Seropositivity decreased
      with age, which might raise possibility of outbreaks among adolescent. Additional
      doses of vaccine against measles and mumps are recommended and evaluation of new
      MMR protocol should be made.

PMID- 16432598
TI  - Associated risk factors with ante-partum intra-uterine fetal death.
AB  - OBJECTIVE: To determine ante-partum maternal risk factors for intrauterine fetal
      death. METHODS: We carried out a case control retrospective study, at the
      Maternity and Children's Hospital, Jeddah, Kingdom of Saudi Arabia. We included
      all pregnant women diagnosed as singleton intra-uterine fetal death in the third
      trimester with fetal weight of 1500 gm and more, admitted to the hospital over a
      2-year (2001-2002) period (study group). We examined the following risk factors:
      diabetes, hypertension, abruptio-placenta, age, gestational age, parity, trauma,
      sepsis, booking, chromosomal abnormality, previous history of intra-uterine fetal
      death (IUFD) and intra-uterine growth restriction (IUGR). We compared the results
      to those pregnant women with live pregnancy admitted before and after each case
      (control group). RESULTS: There were 157 cases of singleton IUFD during that
      period. The intra-uterine fetal death rate was 10.1 per 1000 deliveries. In 28%
      of the cases, we could not determine the associated risk factors. Among cases
      there were 57.3% (odds ratio [OR] 2.4 95% confidence interval [CI] 1.4-4) lacking
      antenatal care, cord accident in 56.6% (OR 5.1% 95 CI 2.7-9.5), 29.3% (OR 5.5 95%
      CI 2.4-12.6) hypertension, 26.1% (OR 12.9 95% CI 5.5-30.6) diabetes, IUGR in
      24.8% (OR 1.73% 95% CI 1.1-2.7), 14% (OR 23.4% 95% CI 4.6-119.3) abruption
      placenta, and previous history of IUFD in 8.3% (OR 7.01 95% CI 2.1-23.6). Other
      risk factors found were age between 20-30 years in 51.6%, gestational age between
      37-41 weeks in 58.6%, parity between 0-5 in 77.1%, and chromosomal abnormality in
      5.7% (OR 0.91% 95% CI 0.91-0.99). CONCLUSION: The identified risk factors for
      IUFD in our community appear preventable. We should pay attention to health
      education with emphasis on antenatal care and the benefits of regular clinic
      attendance. Patients compliance is important in reducing most of these
      preventable fetal deaths.

PMID- 16432599
TI  - The Persian version of the Cardiff Acne Disability Index. Reliability and
      validity study.
AB  - OBJECTIVE: The Cardiff Acne Disability Index (CADI) assesses the impact of acne
      on a patients life. The aim of the present study was to translate the CADI into
      Persian language and to validate the Persian version. METHODS: Using standard
      forward-backward translation, 2 bilinguals translated the CADI into Persian
      language. We back translated it into English and the final version was provided.
      We conducted this study from February through December 2004 on 100 patients with
      acne attending the Department of Dermatology, Jahrom Medical School, Jahrom, Iran
      who completed the Persian version of the CADI questionnaire. We carried out all
      statistical analyses using the Statistical Package for the Social Sciences
      version 11 for Windows. RESULTS: A total of 100 patients (15 men, 85 women) with
      acne participated in this study. The mean age of the patients was 20.76 +/- 2.94
      years. Scores of the CADI ranged from 2-14 (7.57 +/- 2.58). Reliability analysis
      showed a satisfactory result (Cronbachs alpha coefficient = 0.79). Moreover,
      Pearsons correlation coefficient of 0.72 demonstrated the good internal
      consistency of the scale. CONCLUSION: The Persian version of the CADI
      questionnaire is a reliable, valid, and valuable tool for assessing the impact of
      acne on a patient's life.

PMID- 16432600
TI  - Treatment of acne vulgaris with 2% topical tea lotion.
AB  - OBJECTIVE: To use 2% tea lotion as natural plant remedy in the treatment of acne
      vulgaris. METHODS: We conducted this study in the Department of Dermatology and
      Venereology in Baghdad Teaching Hospital, Iraq during the period between October
      2002 and October 2004. In this single blind randomly controlled therapeutic
      study, we enrolled 60 patients, their ages ranged from 14-22 years. There were 35
      females and 25 males. We divided the patients equally into 2 groups; we
      instructed group A to use freshly prepared 2% tea lotion twice daily for 2
      months, while group B used a control solution. We graded the acne vulgaris as
      mild and moderate acne by counting the number of papules and pustules. We carried
      out statistical analysis by computer using t-test, f-test, and chi-square when
      needed. RESULTS: Forty-nine patients completed the study. In group A (25
      patients), we noted a significantly reduced mean lesion count of papules and
      pustules after 2 months of therapy. The response of patients to treatment was
      good in 64%, moderate in 24% and no response in 12%. The satisfaction of patients
      with treatment was full in 64%, partial in 24%, and no satisfaction in 12%. In
      group B (24 patients), the lesions showed no significant reduction after 2 months
      and the response of patients to treatment was good in 20.8%, moderate in 45.8%,
      and no response in 33.4%. The satisfaction of patients with treatment in this
      group was full in 4.2%, partial in 12.5%, and no satisfaction in 83.3%. The mean
      difference in outcome after 8 weeks between the 2 study groups was statistically
      significant. CONCLUSION: The 2% tea lotion has proved its efficacy as a topical
      therapy for acne vulgaris. This is a new natural plant extract, which lacks any
      side effects.

PMID- 16432601
TI  - Epidemiology of travel-related malaria in a non-malarious area in Saudi Arabia.
AB  - OBJECTIVE: The study describes the epidemiology of malaria in the Eastern
      Province of Saudi Arabia and the species of Plasmodium causing the disease and
      the associated factors. METHODS: This is a retrospective study of the
      epidemiology of malaria at Saudi Aramco Medical Services Organization in Dhahran,
      Eastern Province of Saudi Arabia. The study included all patients with malaria
      from January 1994 to June 2005. We retrieved the cases from the archive
      epidemiology records on all notifiable diseases. The medical records of patients
      were reviewed and the following information was collected: age, gender,
      nationality, year and month of acquisition, travel history and the species
      causing malaria. RESULTS: Over the study period from January 1994 to June 2005,
      there were 56 cases of imported malaria seen at Saudi Aramco Medical Services
      Organization. There were 28 males and 28 females with a mean age of 28.2 +/- 19.7
      (range, 1-80) years. Saudis constituted 25% of the patients and the remaining
      (75%) were non-Saudi. Most of the cases (78.7%) were acquired outside Saudi
      Arabia and 21.3% were acquired in the Kingdom but outside the Eastern Province.
      The most frequent species were Plasmodium vivax (P. vivax) (54.4%), Plasmodium
      falciparum (P. falciparum) (43%) and Plasmodium malariae (1.8%). Of the cases
      acquired within other parts of Saudi Arabia, 71.4% were secondary to P.
      falciparum. Acquisition of malaria in India P. falciparum constituted 71.4% and
      in Pakistan 91%. For Sudanese patients, P. falciparum constituted 47% and P.
      vivax was 53%. Most of the non-Saudi cases were seen in the month of September
      (19%) whereas 57% of the Saudi cases were seen in February and April. CONCLUSION:
      There were no active cases of malaria transmission within the Eastern province of
      Saudi Arabia; however, the continued presence of imported malaria into this
      region may pose a significant health problem especially in the presence of the
      malaria vector. Thus, effective treatment and vigilance for cases of malaria is
      needed.

PMID- 16432602
TI  - Antimony-induced cerebellar ataxia.
AB  - Visceral leishmaniasis VL, caused by Leishmania donovani is endemic over several
      parts of Sudan. The disease is fatal if not treated. Although sodium
      stibogluconate Pentostam, a pentavalent antimonial is not free from toxicity, it
      has been in use for treatment of VL for the last 50 years. Like other infectious
      diseases, neurological manifestations of VL and sodium stibogluconate have been
      documented. In this report, we present 2 cases of cerebellar ataxia most likely
      induced by Pentostam, and explain the probable cause.

PMID- 16432603
TI  - Vulvar basal cell carcinoma misdiagnosed for 4 years.
AB  - Vulvar basal cell carcinoma is a rare cutaneous neoplasm occurring mainly in
      white postmenopausal females. It can be misdiagnosed due to its nonspecific
      physical appearance. Here, we report a 59-year-old white female who had vulvar
      basal cell carcinoma misdiagnosed for 4 years.

PMID- 16432604
TI  - Pregnancy complicated by superior vena cava thrombosis and pulmonary embolism in
      a patient with Behcet disease and the use of heparin for treatment.
AB  - Behcet disease is a multisystemic vasculitis of unknown origin. Vascular
      involvement has been considered to result from systemic vasculitis, occurs in 5
      10% of these patients. We report a 34-year-old pregnant woman complicated by
      superior vena cava thrombosis, and pulmonary embolism in a patient with Behcet
      disease.

PMID- 16432605
TI  - Rupture of spleen in a mechanically ventilated patient with falciparum malaria
      admitted with pulmonary edema.
AB  - Rupture of the spleen in malaria may constitute a diagnostic challenge to many
      clinicians particularly in non-endemic areas where experience with malaria is
      limited. Our aim is to increase the awareness among clinicians from non-endemic
      areas of serious malarial complications. We present a young American military man
      who was admitted to Hamad General Hospital and had 2 serious malarial
      complications, namely, acute pulmonary edema and rupture of the spleen. He was
      unusual compared with what was published previously in 4 main points: 1. The
      rupture of spleen occurred while the patient on mechanical ventilation and under
      the effect of sedation, which constituted a diagnostic challenge. 2. The 2
      complications occurred in a patient with a low parasitemia. 3. The causative
      species for splenic rupture is Plasmodium falciparum, and 4. The first sample of
      peripheral blood smear for malarial parasite was negative. We treated him
      successfully and discharged home in a good condition.

PMID- 16432606
TI  - The use of endovascular stent-grafts for the treatment of common carotid-internal
      jugular fistula.
AB  - We report a case of a fistula between the common carotid artery and the internal
      jugular vein due to a hemodialysis catheter insertion. We managed the fistula by
      the insertion of a covered-stent at the common carotid artery, and completely
      sealed the fistula without immediate complications. We present this case to
      highlight this new successful method of treatment.

PMID- 16432607
TI  - Acute disseminated encephalomyelitis in an adult patient. Magnetic resonance and
      diffusion-weighted imaging findings.
AB  - Acute disseminated encephalomyelitis ADEM is an uncommon inflammatory disease of
      the central nervous system and can be defined strictly as scattered focal or
      multifocal disseminated inflammation of brain or spinal cord, or both. An ADEM
      usually reveals patchy demyelinated lesions with a high signal on T2-weighted
      sequences. Here, we report a case of a 39-year-old man with ADEM. Echo-planar
      trace diffusion magnetic resonance imaging revealed high signal intensity changes
      at the lesion sites on b=1000 s/mm2 images, initially suggesting restricted
      diffusion. On corresponding apparent diffusion coefficient ADC maps, however, the
      lesions have a high signal intensity and high ADC values, compared with the
      normal white matter. This was consistent with the presence of elevated diffusion,
      and hence, vasogenic edema.

PMID- 16432608
TI  - Toxic epidermal necrolysis due to co-trimoxazole.

PMID- 16432609
TI  - Clinical paradox. Man versus machine.

PMID- 16432610
TI  - Prilocaine induced methemoglobinemia.

PMID- 16432611
TI  - Intraligamentary solid-cystic neoplasia with histomorphological features of
      sclerosing stromal tumor.

PMID- 16432612
TI  - The factors of arteriovenous fistula failure in hemodialysis patient.

PMID- 16432613
TI  - Dark-lumen magnetic resonance colonography.

PMID- 16432614
TI  - The use of etoricoxib in patients with bronchial asthma associated with aspirin
      sensitivity.

PMID- 16432615
TI  - Diagnostic value of MR imaging in meniscal tears of the knee.

PMID- 16432616
TI  - Intramuscular artemether in the treatment of uncomplicated Plasmodium falciparum
      malaria in Sudanese patients.

PMID- 16432617
TI  - Validity and reliability of the Turkish version of the Ferrans and Powers Quality
      of Life Index: diabetes version.

PMID- 16432618
TI  - Domestic violence experiences among medical students in 2 universities.

PMID- 16432619
TI  - Falls and depression in the elderly population.

PMID- 16432620
TI  - The diagonal ear-lobe crease. As sign of some diseases.

PMID- 16432621
TI  - Metallic magnetic nanoparticles.
AB  - In this paper, we reviewed some relevant aspects of the magnetic properties of
      metallic nanoparticles with small size (below 4 nm), covering the size effects in
      nanoparticles of magnetic materials, as well as the appearance of magnetism at
      the nanoscale in materials that are nonferromagnetic in bulk. These results are
      distributed along the text that has been organized around three important items:
      fundamental magnetic properties, different fabrication procedures, and
      characterization techniques. A general introduction and some experimental results
      recently obtained in Pd and Au nanoparticles have also been included. Finally,
      the more promising applications of magnetic nanoparticles in biomedicine are
      indicated. Special care was taken to complete the literature available on the
      subject.

PMID- 16432622
TI  - Neuroregulation of the hypothalamus-pituitary-adrenal (HPA) axis in humans:
      effects of GABA-, mineralocorticoid-, and GH-Secretagogue-receptor modulation.
AB  - The hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both
      the central and peripheral level. Its activity is mainly regulated by CRH, AVP,
      and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters
      and neuropeptides influence HPA axis activity by acting at the hypothalamic
      and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues
      (GHS)/GHS-receptor systems have been shown to exert a clear inhibitory and
      stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP), a
      GABA-A receptor agonist, shows the most marked inhibitory effect on both
      spontaneous and stimulated HPA axis activity, in agreement with its peculiar
      efficacy in panic disorders and depression where an HPA axis hyperactivation is
      generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol
      releasing effect in humans and the ghrelin/GHS-R system is probably involved in
      the modulation of the HPA response to stress and nutritional/metabolic
      variations. The glucocorticoid-mediated negative feedback action is mediated by
      both glucocorticoid (GR) and mineralocorticoid (MR) receptors activation at the
      central level, mainly in the hippocampus. In agreement with animal studies, MRs
      seem to play a crucial role in the maintenance of the circadian ACTH and cortisol
      rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly
      ALP), ghrelin, as well as MR agonists/antagonists, may represent good tools to
      explore the activity of the HPA axis in both physiological conditions and
      pathological states characterized by an impaired control of the corticotroph
      function.

PMID- 16432623
TI  - Confocal imaging: blood and lymphatic capillaries.
AB  - Traditional imaging techniques are quite limited for the study of the
      relationship between blood vessels and lymphatic vessels. Therefore, a new
      imaging technique is required based on blood vessel and lymphatic endothelial
      specific molecular markers. In this short report, vascular molecular markers are
      reviewed and a new molecular imaging technique for blood vessel and lymphatic co
      staining is introduced.

PMID- 16432624
TI  - Respiratory distress secondary to esophageal foreign body: a case report.
AB  - The ingestion or aspiration of a foreign body is a common, but preventable
      occurrence in childhood. Primary healthcare personnel should alert parents to the
      risk of swallowing a foreign object, the signs and the need for immediate medical
      attention. It should be emphasized that protecting children from access to
      objects that can be swallowed or aspirated is the best preventive measure. A case
      of an eight year old child, who had swallowed a marble ball is presented and the
      symptoms and intervention discussed. Medical staff should be aware of the
      symptomatic variation in ingested foreign body presentation and the importance of
      rapid diagnosis and management.

PMID- 16432625
TI  - Electrochemical study of biotin-modified self-assembled monolayers:
      recommendations for robust preparation.
AB  - The development of the underpinning methodology for the production of robust,
      well-formed, and densely packed biotin-HPDP functionalised gold surfaces, the
      crucial first step in immobilising bimolecules on surfaces, is described. Self
      assembled monolayers (SAMs) with biotin end-groups were prepared on
      polycrystalline gold surfaces according to a published method. The layers formed
      were studied using cyclic voltammetry to determine the composition of the layer
      and its quality. Crystal impedance spectroscopy was also applied as a
      complimentary indicator of the composition of the layer. For the first time, the
      effect of assembly time on the properties of the layer was studied along with the
      composition of the layer and the ability of the precursor molecule to self
      assemble by oxidative addition.

PMID- 16432626
TI  - Parental knowledge on car safety for children: an Israeli survey.
AB  - The objective of this study was to assess the level of parental car safety
      knowledge and actual behavior regarding their children under the age of 15 years.
      This study forms part of the National Center for Child Safety and Health in
      Israel (Beterem) program to examine awareness on child safety. Seven hundred and
      five Jewish families with at least one child at home younger than 15 years (a
      total of 1,345 children) were used as a randomized sample of the Jewish
      population. A telephone survey was conducted by professional interviewers using a
      questionnaire developed by injury prevention specialists consisting of seven
      knowledge questions and a diagram that described the usual seating positions and
      restraining method of the family members in the family car. Concerning knowledge
      about injury prevention, the rate of incorrect answers was high, 64% in regard to
      the proper car seats for age and 84% in regard to the age for booster seats.
      Sixty five percent of parents did not know what a booster seat was and 54% did
      not know that the proper place for children was in the back seat. The average of
      incorrect answers was 4.86 out of 7 (SD=1.45) correlated with low socioeconomic
      status. Concerning care safety behavior 60% percent of babies and 38% of toddlers
      were not restrained properly. This study should alert planners and policy makers
      to the need of implementation of educational prevention programs for the Israeli
      public of parents concerning car safety for children in order to reduce childhood
      injury.

PMID- 16432627
TI  - A novel 110-kDa receptor protein is involved in endocytic uptake of decorin by
      human skin fibroblasts.
AB  - The small leucine-rich proteoglycan (SLRP) decorin is efficiently internalized by
      a variety of cultured cells. A 51-kDa protein has previously been described as a
      receptor mediating endocytosis of decorin and of the structurally related SLRP
      biglycan. Recent findings suggest that endocytosis of SLRPs may also be mediated
      by additional receptors. The class-A scavenger receptor, the endocytic mannose
      receptor, the epidermal growth factor receptor, and insulin-like growth factor-I
      receptor have emerged as candidates. We used a combined approach of
      immunoprecipitation and photoactivated cross-linking to identify endocytosis
      receptors for decorin in human skin fibroblasts. Decorin was purified by HPLC
      DEAE-ion exchange chromatography from the secretions of human skin fibroblasts
      under nondenaturing conditions. Confocal immunofluorescence microscopy revealed
      that both biotinylated decorin and decorin conjugated to the heterobifunctional
      cross-linker sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1-3'-dithiopropionate
      (SASD) were endocytosed with equal efficiency. SASD-conjugated decorin was added
      to [35S]-methionine-labeled fibroblasts and cross-linked intracellularly to
      receptor molecules by photoactivation on endocytic uptake. Cross-linked decorin
      receptor complexes were purified from the extracts of trypsin-treated fibroblasts
      by anion exchange chromatography and immunoprecipitation with a decorin-specific
      antiserum. Analysis by 2D electrophoresis and autoradiography revealed that
      decorin was specifically cross-linked to a protein of 110 kDa, which exhibited an
      isoelectric point of 5.5. In a second approach, unlabeled fibroblasts were
      subjected to decorin endocytosis and photoactivated cross-linking followed by
      Western blotting of DEAE-purified cell extracts. A shift of biotinylated decorin
      immunoreactivity from 165 kDa (decorin-receptor complex) to 54 kDa (SASD
      conjugated biotinylated decorin) was noted on reductive cleavage of the cross
      linker, representing a difference in molecular weight of approximately 110 kDa.
      The identification of a 110-kDa protein as a novel endocytosis receptor for
      decorin provides further support for the emerging concept of a redundancy of
      receptor molecules in the endocytosis of SLRP.

PMID- 16432628
TI  - Aspects of growth hormone and insulin-like growth factor-I related to
      neuroprotection, regeneration, and functional plasticity in the adult brain.
AB  - Apart from regulating somatic growth and metabolic processes, accumulating
      evidence suggests that the growth hormone (GH)/insulin-like growth factor-I (IGF
      I) axis is involved in the regulation of brain growth, development, and
      myelination. In addition, both GH and IGF-I affect cognition and biochemistry in
      the adult brain. Some of the effects of GH are attributable to circulating IGF-I,
      while others may be due to IGF-I produced locally within the brain. Some of the
      shared effects in common to GH and IGF-I may also be explained by cross-talk
      between the GH and IGF-I transduction pathways, as indicated by recent data from
      other cell systems. Otherwise, it also seems that GH may act directly without
      involving IGF-I (either circulating or locally). Plasticity in the central
      nervous system (CNS) may be viewed as changes in the functional interplay between
      the major cell types, neurons, astrocytes, and oligodendrocytes. GH and IGF-I
      affect all three of these cell types in several ways. Apart from the
      neuroprotective effects of GH and IGF-I posited in different experimental models
      of CNS injury, IGF-I has been found to increase progenitor cell proliferation and
      new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the
      hippocampus. It appears that the MAPK signaling pathway is required for IGF-I
      stimulated proliferation in vitro, whereas the PI3K/Akt or MAPK/Erk signaling
      pathway appears to mediate antiapoptotic effects. The increase of IGF-I on
      endothelial cell phenotype may explain the increase in cerebral arteriole density
      observed after GH treatment. The functional role of GH and IGF-I in the adult
      brain will be reviewed with reference to neurotransmitters, glucose metabolism,
      cerebral blood flow, gap junctional communication, dendritic arborization,
      exercise, enriched environment, depression, learning, memory, and aging. Briefly,
      these findings suggest that IGF-I functions as a putative regenerative agent in
      the adult CNS. Hitherto less studied regarding in these aspects, GH may have
      similar effects, especially as it is the main regulator of IGF-I in vivo. Some of
      the positive cognitive features of GH treatment are likely attributable to the
      mechanisms reviewed here.

PMID- 16432629
TI  - Comparative analysis of methylthioalkylmalate synthase (MAM) gene family and
      flanking DNA sequences in Brassica oleracea and Arabidopsis thaliana.
AB  - Gene BoGSL-PRO is associated with presence of 3-carbon side-chain glucosinolates
      (GSL). This gene is a member of the methylthioalkylmalate synthase (MAM) gene
      family. A BAC clone of Brassica oleracea, B21F5, containing this gene, was
      sequenced, annotated and compared to its corresponding region in Arabidopsis
      thaliana. Twelve protein-coding genes and 10 transposable elements were found in
      this clone. The corresponding region in A. thaliana chromosome I has 14 genes and
      no transposable elements. Analysis of MAM gene family in both species, which also
      include genes controlling 4-carbon side-chain GSL, separated the genes in two
      groups based on exon numbers and function. Phylogenetic analysis of the amino
      acid sequences encoded by these genes suggest that these two groups were produced
      by a duplication that must have occurred before the divergence of the Rosid and
      Asterid lineages of angiosperms. Comparison with putative orthologs from several
      prokaryotes further suggest that the members of the gene family with 10 exons,
      which encode proteins involved in 4-carbon side-chain GSL biosynthesis, were
      derived via truncation of the 3' end from ancestral genes more similar in length
      to those with 12 exons, which encode proteins involved in 3-carbon side-chain GSL
      biosynthesis. Lower gene density in B. oleracea compared to A. thaliana is due in
      part to presence of transposable elements (TE) mostly in inter-genic regions.

PMID- 16432630
TI  - Precursor limitations in methyl jasmonate-induced Catharanthus roseus cell
      cultures.
AB  - Jasmonates enhance the expression of various genes involved in terpenoid indole
      alkaloid (TIA) biosynthesis in Catharanthus roseus. We applied precursor feeding
      to our C. roseus suspensions to determine how methyl jasmonate (MJ) alters the
      precursor availability for TIA biosynthesis. C. roseus suspensions were induced
      with MJ (100 microM) on day 6 and fed loganin (0.30 mM), tryptamine (0.15 mM),
      loganin plus tryptamine, or geraniol (0.1-1.0 mM) on day 7. While MJ increased
      ajmalicine production by 3-fold, induced cultures were still limited by terpenoid
      precursors. However, both induced and non-induced cultures became tryptamine
      limited with excess loganin. Geraniol feeding also increased ajmalicine
      production in non-induced cultures. But MJ appeared to increase geraniol
      availability in induced cultures, due presumably to the increased expression of
      Dxs with MJ addition.

PMID- 16432631
TI  - A tissue culture system for different germplasms of indica rice.
AB  - Agrobacterium-mediated transformation of indica rice has been manipulated in only
      a limited number of cultivars because the majority of indica varieties are
      recalcitrant to in vitro response. Establishment of a highly efficient and widely
      used tissue culture system for indica rice will accelerate the application of
      transformation technology in breeding programs and the study of the functions of
      indica-specific genes. By manipulating plant growth regulators, organic
      components and salts within the culture media, we established two media for
      callus induction and subculture, respectively, in tissue culture of indica rice.
      The modified media could guarantee the production and proliferation of a great
      number of embryogenic calli with high regeneration capacity from mature seeds
      representing different indica rice germplasms. The calli obtained from this
      system should be ideal material for Agrobacterium-mediated transformation. The
      results suggest that this optimized tissue culture system will be widely
      applicable for the tissue culture of indica varieties.

PMID- 16432633
TI  - Impact of decisional capacity on the use of leverage to encourage treatment
      adherence.
AB  - Leverage is often applied to persons with mental illnesses who live in the
      community to encourage them to adhere to treatment. Given the underlying
      assumption that the targets of such leverage are unable to make good decisions
      about treatment on their own, one might expect that decisional incapacity
      regarding treatment would correlate with the use of leverage. As part of a multi
      site study of leverage in community treatment, 120 subjects at two sites reported
      on their leverage experiences and completed a decisional capacity assessment with
      the MacCAT-T. No strong or consistent associations were found between capacity
      and use of leverage, raising questions about the basis on which decisions to
      employ leverage are being made.

PMID- 16432632
TI  - Transmission disequilibrium test provides evidence of association between
      promoter polymorphisms in 22q11 gene DGCR14 and schizophrenia.
AB  - Recent research has suggested that the DiGeorge syndrome critical region gene 14
      (DGCR14) exhibits activity differences of more than 1.5 fold between the
      haplotypes of the variants in the promoter region. DGCR14 is located at 22q11.21,
      an acknowledged region for susceptibility to schizophrenia. To test the
      hypothesis that DGCR14 may be involved in the etiology of the disease, we carried
      out a family-based association study between the reported functional markers and
      schizophrenia in 235 Chinese Han trios. We found significant evidence of
      preferential transmission of the promoter variants of DGCR14 across all the trios
      (Best p-value = 0.00038, Global p-value = 0.0008). The positive results have
      suggested that DGCR14 is likely to play an important role in the etiology of
      schizophrenia in the Chinese Han population.

PMID- 16432634
TI  - Functional stability of microbial communities in contaminated soils near a zinc
      smelter (Budel, the Netherlands).
AB  - Environmental pollution causes adverse effects on many levels of ecosystem
      organization; it might affect the use efficiency of available resources which
      will make the system more sensitive to subsequent stress. Alternatively the
      development of community tolerance may make the system more resistant to
      additional stresses. In this study we investigate the functional stability,
      measured in the terms of resistance and resilience, of microbial populations
      inhabiting contaminated soils near a zinc smelter. With functional stability we
      mean that we look at processes rather than at population dynamics. We measure
      changes in respiration and bacterial growth rate in response to addition of
      stress (lead, salt) or disturbance (heat). We used soils that differ in the level
      of pollution with zinc and cadmium originating from an adjacent smelter. Our
      results showed, with regard to respiration, that the most polluted soils have the
      lowest stability to salt (stress) and heat (disturbance). This confirms the
      hypothesis that more stressed systems have less energy to cope with additional
      stress or disturbance. However, bacterial growth rates were affected in a
      different way than respiration. There was no difference between the soils in
      resistance and resilience to addition of lead. In case of salt treatment, the
      least polluted soils showed highest stability. In contrast, the least polluted
      soils were the least stable to increased temperature, which supports the
      hypothesis that more stressed soils are more stable to additional
      stress/disturbance due to properties they gained when exposed to the first stress
      (pollution by the smelter). Thus, the responses of microbial processes to stress,
      their nature and size, depend on the kinds of stress factors, especially whether
      a subsequent stress is similar to the first stress, in terms of the mechanism
      with which the organisms deal with the stress.

PMID- 16432635
TI  - Solid-like rheological response of non-entangled polymers in the molten state.
AB  - We show that non-entangled polymers display an elastic-like behaviour at a
      macroscopic scale (probed at some 0.100 mm thickness) up to at least hundred
      degrees above the glass transition temperature. This observation, found under non
      slippage conditions, both for side-chain liquid crystalline polymers and ordinary
      polymers, is in contradiction with the typically found flow behaviour of polymer
      melt. Our measurements were carried out with a conventional rheometer at
      thicknesses of several tenths millimetres. Thus, we were probing bulk properties.
      The observed elasticity supposedly implies that even in the melt the chains
      experience a cohesive effect of macroscopic distances, involving collective
      motions over time scales longer than the individual relaxation time of an
      individual polymer chain. The detection of such a solid-like property of molten
      non-entangled polymers is of considerable importance for a better understanding
      of the polymer dynamics.

PMID- 16432636
TI  - An association study of asthma and related phenotypes with polymorphisms in
      negative regulator molecules of the TLR signaling pathway.
AB  - Although associations between endotoxin exposure or respiratory infection and
      asthma have been recognized, the genetic effects in these conditions are unclear.
      Toll-like receptors (TLRs) play an essential role in innate host defense and in
      the control of adaptive immune responses. IL-1R-associated kinase-M (IRAK-M) and
      single immunoglobulin IL-1R-related molecule (SIGIRR) negatively regulate TLR
      signaling pathways. To investigate whether polymorphisms in these genes were
      associated with asthma or asthma-related phenotypes, we screened these genes for
      polymorphisms by direct sequencing of 24 asthmatics and identified 19 variants in
      IRAK-M and 12 variants in SIGIRR. We next conducted linkage disequilibrium
      mapping of the genes, and examined the association of polymorphisms and
      haplotypes using 391 child patients with asthma, 462 adult patients with asthma,
      and 639 controls. None of the alleles or haplotypes of IRAK-M and SIGIRR were
      associated with asthma susceptibility or asthma-related phenotype. Our results
      indicate that polymorphisms in IRAK-M and SIGIRR are not likely to be associated
      with the development of asthma in the Japanese population.

PMID- 16432637
TI  - Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in
      Japanese patients.
AB  - Warfarin is the most commonly used oral anticoagulant for treatment of
      thromboembolism, but adjustment of the dose appropriate to each patient is not so
      easy because of the large inter-individual variation in dose requirement. We
      analyzed single nucleotide polymorphism (SNP) genotypes of the VKORC1 and CYP2C9
      genes using DNA from 828 Japanese patients treated with warfarin, and
      investigated association between SNP genotype and warfarin-maintenance dose. Five
      SNPs in VKORC1, 5' flanking-1413A > G, intron 1-136T > C, intron 2+124C > G,
      intron 2+837T > C and exon 3 343G > A, were in absolute linkage disequilibrium,
      and showed a significant association with daily warfarin dose of these patients.
      The median warfarin dose of patients with homozygosity for the minor allele was
      4.0 mg/day, which is significantly higher than those heterozygous for the minor
      allele (3.5 mg/day) or those homozygous for the major allele (2.5 mg/day; P = 5.1
      x 10(-11) in the case of intron 1-136T > C SNP). We then genotyped the CYP2C9
      gene for the Japanese common genetic variant, CYP2C9*3 and, based on the genotype
      of these two genes, classified patients into three categories, which we call
      "warfarin-responsive index." The median warfarin daily dose varied significantly
      in this classification according to the warfarin-responsive index (2.0 mg/day for
      index 0 group, 2.5 mg/day for index 1 group, and 3.5 mg/day for index 2 group; P
      = 4.4 x 10(-13)). Thus, analysis of the combination of VKORC1 and CYP2C9
      genotypes should identify warfarin-sensitive patients who require a lower dose of
      drug, allowing personalized warfarin treatment.

PMID- 16432638
TI  - Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for
      selective tooth agenesis.
AB  - Selective tooth agenesis is the most common developmental abnormality of the
      human dentition. To date, this abnormality has been associated only with
      mutations in MSX1 and PAX9 mutations, however it has recently been suggested that
      mutations of axis inhibition protein 2 (AXIN2) may also contribute to this
      complex anomaly. The protein product of this gene is a negative regulator of the
      Wnt-signaling pathway. We searched for AXIN2 variants in a group of patients with
      tooth agenesis who did not have mutations of MSX1 and PAX9. Using multi
      temperature single-stranded conformational polymorphism and sequencing analysis,
      we identified three novel AXIN2 gene variants: c.956+16A > G, c.1060-17C > T and
      c.2062C > T. We also observed that individuals carrying the c.956+16G and c.2062T
      alleles exhibited an increased risk of tooth agenesis. The calculated odds ratio
      was 2.94 (95% CI 1.104-7.816; p = 0.026; p(corr) = 0.234) and 4.01 (95% CI 1.563
      10.301; p = 0.002; p(corr) = 0.018), respectively. Moreover, we found that the
      c.2062C > T transition may change exon splice enhancer-specific binding sites of
      the protein splicing regulators SC35 and SF2/ASF. This alternation may negatively
      affect the splicing process and cellular concentration of AXIN2 protein. Our
      findings suggest that AXIN2 polymorphic variants may be associated with both
      hypodontia and oligodontia.

PMID- 16432639
TI  - Not only annual food abundance but also fallback food quality determines the
      Japanese macaque density: evidence from seasonal variations in home range size.
AB  - Previous studies on Japanese macaque (Macaca fuscata) densities suggest that both
      total annual food abundance and the quality of fallback foods in the winter
      bottleneck period affects density. We reviewed data on the seasonal changes in
      home range size to explain how both factors affect density. In general, home
      range was large in summer or autumn and small in spring or winter, indicating
      that density is determined by the home range size in the seasons before winter.
      The main foods in these seasons are fruits and seeds. If these foods are not
      abundant, macaques need to range over a larger area, thus decreasing density.
      Macaques survive the winter by depending on the fat deposited before winter
      through eating these high-quality foods. If the food condition in winter is
      severe and the amount of required fat deposition is large, macaques need a larger
      home range before winter, and thus density becomes lower.

PMID- 16432640
TI  - A new mark test for mirror self-recognition in non-human primates.
AB  - For 30 years Gallup's (Science 167:86-87, 1970) mark test, which consists of
      confronting a mirror-experienced test animal with its own previously altered
      mirror image, usually a color mark on forehead, eyebrow or ear, has delivered
      valuable results about the distribution of visual self-recognition in non-human
      primates. Chimpanzees, bonobos, orangutans and, less frequently, gorillas can
      learn to correctly understand the reflection of their body in a mirror. However,
      the standard version of the mark test is good only for positively proving the
      existence of self-recognition. Conclusive statements about the lack of self
      recognition are more difficult because of the methodological constraints of the
      test. This situation has led to a persistent controversy about the power of
      Gallup's original technique. We devised a new variant of the test which permits
      more unequivocal decisions about both the presence and absence of self
      recognition. This new procedure was tested with marmoset monkeys (Callithrix
      jacchus), following extensive training with mirror-related tasks to facilitate
      performance in the standard mark test. The results show that a slightly altered
      mark test with a new marking substance (chocolate cream) can help to reliably
      discriminate between true negative results, indicating a real lack of ability to
      recognize oneself in a mirror, from false negative results that are due to
      methodological particularities of the standard test. Finally, an evolutionary
      hypothesis is put forward as to why many primates can use a mirror instrumentally
      - i.e. know how to use it for grasping at hidden objects - while failing in the
      decisive mark test.

PMID- 16432641
TI  - Cooling for the reduction of postoperative pain: prospective randomized study.
AB  - Hernia surgery has been associated with severe pain within the first 24 h
      postoperatively. The application of cold or cryotherapy has been in use since at
      least the time of Hippocrates. The physiological and biological effects from the
      reduction of temperature in various tissues include local analgesia, inhibited
      oedema formation and reduced blood circulation. Our hypothesis was that cold
      therapy, applied by means of ice packs, following inguinal hernia surgery,
      controlled pain postoperatively. Forty patients scheduled for inguinal hernia
      repair were enrolled in a double-blind, randomized study. Postoperatively,
      chipped ice in a plastic bag (cold group), and a plastic bag containing only room
      temperature water (control) were placed over the incision for 20 min.
      Postoperative pain data were collected at 2, 6 and 24 h after operation according
      to the well validated visual analogue scale (VAS). The highest pain levels were
      recorded 2 h postoperatively for both groups. Pain levels then gradually
      decreased for both the trial groups during the first 24 h postoperatively. There
      were significant differences in the VAS scores between the groups at 2, 6 and 24
      h. We conclude that local cooling is a safe and effective technique for providing
      analgesia following inguinal hernia repair.

PMID- 16432642
TI  - Stoppa procedure in bilateral inguinal hernia.
AB  - The Stoppa procedure is a very safe repair of bilateral inguinal hernia, but it
      requires a learning period to achieve optimal results. We present a study with
      our experience and learning curve for this technique. Two hundred and ten
      patients with bilateral inguinal hernia (420 hernias) were repaired with Stoppa
      procedure from January 1995 to December 2003 with an average age of 57.2 years
      (range 28-89 years), with 8 women and 202 men (96%). Emergency surgery was
      performed for incarcerated hernia in six cases (2.8%). The rates of recurrent
      hernias, concomitant disease and associated surgical techniques were similar in
      all the years. Operative time decreased from 100 min (1995) to 61-66 min (2001
      2003). Drain remained in place in 100% (1995), and 0% (2003). Regional
      anaesthesia was performed in 25% (1995) and 80-90% in the last years; hospital
      stay decreased from 5.1 to 1.2 days (2003), and morbidity from 50% (1995) to 12
      16% (P<0.0001). There were three recurrences, two in the first 30 cases (6.6%),
      and one in the remaining 180 (0.5%) (4-92 months follow-up). The procedure was
      introduced in 1995 by one surgeon, performing 100% of cases, being accepted
      progressively by other surgeons. The first 25-30 cases of a surgical technique
      are the learning curve, with the highest rate of morbidity, time, technical and
      operative difficulties, and long hospital stay. As a result of the first
      surgeon's experience, some modifications of the technique are developed and
      results improved.

PMID- 16432643
TI  - Morphological characteristics of the infraorbital foramen and infraorbital canal
      using three-dimensional models.
AB  - Infraorbital nerve blocking through the infraorbital foramen and infraorbital
      canal is used to anesthetize the lower eyelid, upper lip, lateral nose, upper
      teeth and related gingivae. For this, it is important to know the position of the
      infraorbital foramen, structures around the foramen, and the direction of the
      injecting needle related to the angle of the infraorbital canal. Many reports
      have described the anatomical location of the infraorbital foramen; however, not
      many have described the angle of the infraorbital canal and those structures
      around the infraorbital foramen that help the physician visualize the correct
      direction of the needle. Dried skulls of 42 Korean subjects (27 male and 15
      female) were studied to analyze structures around the infraorbital foramen. The
      morphology of the infraorbital canal was also investigated using three
      dimensional models. Structures around the infraorbital foramen were classified
      into four types according to the existence of a distinct tuberosity above the
      infraorbital foramen, and the degree of prominence of the canine fossa. Types I
      and II have a tuberosity above the infraorbital foramen, whereas types III and IV
      have no distinct tuberosity. Types I and III have a prominent canine fossa,
      whereas this is less prominent in types II and IV. We analyzed the skulls based
      on the angle of the infraorbital canal to the median plane. We compared the left
      and right sides and analyzed differences between the sexes, the three canal
      shapes, and the four structure types around the infraorbital foramen. Type IV was
      the most common in this series (38%). The infraorbital canal could be classified
      into three morphologies: 'tube-like' (69%), 'funnel' (25%) and 'pinched' (6%).
      The mean angle of the infraorbital canal relative to the median plane was 12
      degrees , and the angle relative to the Frankfurt plane was 44 degrees . The mean
      angle between the infraorbital canal and the Frankfurt plane was 4 degrees larger
      in males than in females in this series of Korean subjects. The operator of the
      infraorbital nerve block should pay attention towards directing the needle upward
      at an angle of about 44 degrees for avoiding nerve damage and consider the
      different angles of the canal according to the individual's sex.

PMID- 16432644
TI  - A randomized controlled trial of mailed osteoporosis education to older adults.
AB  - INTRODUCTION: Osteoporosis represents a growing public health concern; however,
      current rates of management are sub-optimal. The aim of our study was to assess,
      in a randomized controlled trial, the effect of a mailed educational intervention
      on older adults' knowledge, attitudes, and preventive behaviors regarding
      osteoporosis. The setting was a large publicly funded state pharmacy benefits
      program. The patients were 31,715 Medicare beneficiaries from Pennsylvania who
      participated in a drug benefits program for low-to-moderate income elderly
      people. METHODS: All women aged over 65 years, and all men and women with a
      history of fracture or long-term oral use of glucocorticoid, were included.
      Approximately half of the participants (intervention group) were randomly
      selected to receive three mailings aimed at improving knowledge of osteoporosis
      and enhancing preventive activities, such as using calcium and vitamin D,
      reducing fall risks in the home, obtaining a bone mineral density (BMD) test, and
      taking medications when necessary. The other participants did not receive the
      intervention mailings and served as controls. We surveyed a sample of
      intervention and control subjects to determine the effects of the intervention on
      knowledge, attitudes, self-efficacy (confidence in one's ability to perform
      specific activities), and behavior regarding osteoporosis prevention and
      treatment. Six hundred randomly selected participants in the intervention group
      and an equal number in the control group were invited to participate. RESULTS:
      Twenty-six had died and 636 of the remaining 1,185 (54%) completed the survey.
      Respondents and non-respondents did not differ significantly with respect to
      measured sociodemographic factors. All scales had good reliability (all
      Cronbach's alphas>0.65). Knowledge of osteoporosis was generally very good and
      did not differ between intervention (mean=65% correct responses) and control
      subjects (mean=67% correct; P=0.4). Perceived susceptibility to osteoporosis was
      relatively high and similar across groups (P=0.4). Self-efficacy for
      participating in osteoporosis prevention and treatment was very strong in both
      the intervention (mean=4.3 on a 0-5 scale) and control (mean=4.2, P=0.03) groups
      . On average, subjects in the intervention group reported participating in 3.5 of
      6 preventive osteoporosis activities compared with 3.4 in the control group
      (P=0.5). CONCLUSIONS: Compared with the controls, a mailed educational
      intervention for osteoporosis was not associated with better knowledge, higher
      perceived susceptibility, or performance of preventive measures among the at-risk
      older adults that we studied. The intervention group demonstrated a small
      increase in self-efficacy. More intensive patient interventions or intervention
      aimed at other aspects of the care process may be required to bring about changes
      that lead to a reduction in fractures.

PMID- 16432645
TI  - Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone
      mineral density in white men or women.
AB  - INTRODUCTION: Peak bone mineral density (BMD) achieved during adulthood is a
      major determinant of osteoporotic fracture in later life. Although environmental
      factors affect peak BMD, it is a highly heritable trait. Recently, bone
      morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for
      osteoporotic fractures and low BMD in Icelandic and Danish populations. METHODS:
      To determine whether polymorphisms in the BMP2 gene contribute to BMD variation
      in our population of healthy American whites, we tested seven single nucleotide
      polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes
      in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were
      measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and
      1,291 pre-menopausal women (age 20-50). SNP genotypes/haplotypes were tested for
      population-based association with BMD using analysis of variance. RESULTS: None
      of the polymorphisms tested reached statistical significance (all p values >0.05)
      for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP
      haplotypes spanning the entire BMP2 gene were marginally associated with BMD in
      men (p values=0.019-0.043). However, these haplotypes would account for only a
      small, if any, portion of BMD variation and would not be significant after
      adjustment for multiple comparisons. CONCLUSIONS: These results demonstrate that
      genetic variations in BMP2 do not substantially contribute to BMD variation in
      our population of healthy American whites.

PMID- 16432646
TI  - Increased bone fracture prevalence in postmenopausal women suffering from pollen
      allergy.
AB  - INTRODUCTION: Our aim was to investigate whether pollen-allergy can affect bone
      mass and fractures in postmenopausal women. METHODS: A total of 125
      postmenopausal pollen-allergic women (mean age: 61.26 yr) were split into four
      groups: (1) treated with neither H1 histamine receptor (H1R) antagonist nor
      inhaled corticosteroid (n=43); (2) treated only with H1R antagonist (n=53); (3)
      treated with both H1R antagonist and inhaled corticosteroid (n=17); (4) treated
      with only inhaled corticosteroid (n=12). Treatment, in the appropriate groups,
      had occurred for at least 5 years, seasonally. One-hundred non-allergic
      postmenopausal subjects matched for age, body mass index (BMI), and age at
      menopause served as controls. RESULTS: Overweight and obesity (25 kg/m(2) < or
      =BMI) were common among the allergic women (76%). Allergic patients without
      treatment had a slightly lower bone density than their non-allergic counterparts.
      The rate (34.9%) of prevalent low-energy fractures (distal forearm, hip, and
      clinical vertebral fractures) in untreated allergic patients was almost triple
      that observed in non-allergic women (13%, chi(2) p=0.003). Bone fracture occurred
      more often in H1R-only treated patients (30.19%) than in controls (chi(2)
      p=0.01); however, clinical vertebral or hip fractures developed neither in those
      treated only with H1R antagonist nor in those who received both H1R antagonist
      and inhaled corticosteroid. Bone fractures were more frequent among patients with
      inhaled steroid treatment than among patients with a combined treatment of
      inhaled steroid and antihistamine (50 versus 29.4%). BMI predicted prevalent
      fractures at 1.278 (95% CI: 1.047-1.559, p=0.016) for a 1 kg/m(2) increase among
      untreated allergic patients. CONCLUSION: In conclusion, we found a high
      prevalence of low-energy fractures among pollen-allergic postmenopausal women
      which was associated with obesity. It is possible that the H1R antagonists
      compensate for both the negative effect of pollen-allergy and the adverse effect
      of inhaled corticosteroid treatment on bone fracture risk.

PMID- 16432647
TI  - Hand-assisted laparoscopic sigmoid resection for diverticular disease: 100
      consecutive cases.
AB  - BACKGROUND: Hand-assisted laparoscopic surgery (HALS) has been proposed as a
      useful alternative to conventional laparoscopic and open surgery. As compared
      with conventional laparoscopic surgery, it offers the advantages of tactile
      feedback, better exposure, and a shorter learning curve. There is increasing
      evidence that HALS retains the advantages of minimal-access surgery. The aim of
      this study was to analyze the feasibility as well as the short- and medium-term
      outcomes of HALS sigmoid resection for diverticular disease. METHODS: The study
      included 100 consecutive patients between July 1999 and August 2004. Data were
      prospectively recorded. Follow-up evaluation was performed by standardized
      telephone interview after a mean postoperative period of 19 months (range, 2-55
      months). RESULTS: Two major intraoperative complications occurred: splenic
      laceration requiring splenectomy and ureteral injury requiring suture. There were
      only three conversions: one case of pararectal incision and two cases of extended
      lower Pfannestiel incision. There was no single case of conversion to midline
      laparotomy. One patient died postoperatively of myocardial infarction. The
      postoperative complications included intraabdominal hematoma (2%), anastomotic
      leakage (3%), wound infection (11%) and bladder dysfunction (1%). The reoperation
      rate was 5%. The median hospital stay was 8 days. In terms of satisfaction with
      the results, 97% of patients would choose HALS again. CONCLUSIONS: When used for
      diverticular disease, HALS sigmoid resection has a low intra- and postoperative
      complication rate. The satisfaction rate among patients is high. Even in
      technically difficult cases, conversion to midline laparotomy can be avoided.

PMID- 16432648
TI  - It is not worthwhile to perform ileoscopy on all patients.
AB  - BACKGROUND: It remains controversial whether ileoscopy should be attempted in all
      patients. Although the ease of ileoscopy and the diagnostic yield have been well
      described, there have been no studies describing the value of the diagnostic
      yield in altering clinical management. We carried out a study to ascertain
      whether it is worthwhile to perform ileoscopy in all patients having a
      colonoscopy. METHODS: We carried out a retrospective study of all patients who
      had a colonoscopy between January 1, 2002, and December 31, 2003. The patient
      details, indications, findings, and complications of the procedure were recorded,
      together with the histopathology reports of colonic and terminal ileal biopsies.
      Clinical case note of patients with a positive diagnosis was reviewed to
      ascertain whether there was a change to the patient's management following an
      abnormal biopsy result. RESULTS: A total of 2,149 colonoscopies were performed.
      In 346 patients (16.1%), the terminal ileum was intubated. There were 16 abnormal
      findings on histology, which gave a diagnostic yield of 4.6% of all ileoscopies.
      A change to management occurred in only half of these patients. CONCLUSION:
      Ileoscopy should only be attempted in situations in which the indication is
      warranted and that would alter management. It is not cost-effective to carry out
      ileoscopy on all patients.

PMID- 16432649
TI  - Gender differences in postoperative pain after laparoscopic cholecystectomy.
AB  - BACKGROUND: Some evidence suggests that females have a lower pain threshold and a
      lower tolerance to painful stimuli. This study investigated gender differences in
      postoperative pain after laparoscopic cholecystectomy (LC) on the basis of visual
      analog pain scale (VAS) scores and the clinical course. METHODS: The 100 patients
      in this study (46 males and 54 females) underwent LC for cholecystolithiasis or
      gallbladder polyps without intraoperative complications. An 8-mm Penrose drain
      was retained for 42 h below the liver bed. All the patients were hospitalized for
      4 days after LC, and the pain reported by patients, the time course of changes in
      the highest body temperature, the leukocyte count, and the C-reactive protein
      level were studied comparatively for the male and female patients. RESULTS: The
      VAS scores were significantly higher for the female patients than for the male
      patients at 24 h (62.7 +/- 24.6 vs 47.0 +/- 23.3; p = 0.0015) and at 48 h (39.2
      +/- 24.3 vs 28.3 +/- 19.1; p = 0.0137) after LC. The female patients used
      analgesics more frequently and had significantly higher body temperatures than
      the male patients on day 1 (37.2 +/- 0.6 vs 36.9 +/- 0.4; p = 0.0037) and day 2
      (36.9 +/- 0.6 vs 36.6 +/- 0.4; p = 0.0037) after surgery. CONCLUSIONS: Early
      postoperative pain after LC was more severe in female patients, and patients with
      high VAS scores tended to use analgesics more frequently.

PMID- 16432650
TI  - Laparoscopic partial myectomy: an experimental reflux model.
AB  - BACKGROUND: A number of different surgical procedures have been described for the
      treatment of gastroesophageal reflux disease. Moreover, modifications and
      completely new techniques are being introduced on a regular basis. Nonetheless,
      in most cases of novel laparoscopic techniques profound experimental data have
      not been collected prior to their clinical introduction. Due to the lack of an
      animal model of inadequate esophageal sphincter function, most experimental
      studies on antireflux procedures were done on normally functioning esophageal
      sphincters. METHODS: It is well-known that myotomy alone cannot induce sphincter
      insufficiency in animal models. In addition, complete myectomy is associated with
      severe mortality and, therefore, is not useful as an experimental model. This
      study introduces a new model of laparoscopic partial in vivo myectomy. The
      procedure described here forms a myectomy of the esophagus using scissors and a
      sponge on the side of the greater gastric curvature. The size of the myectomy is
      approximately 6 x 1.5 cm and was successfully performed in a consecutive series
      of eight experimental animals (male German house pigs). RESULTS: Following an
      intensive team training on dead animals, the procedure was performed with success
      via the laparoscope in all study animals (n = 8). The sphincter pressure as
      determined by manometry was significantly reduced from 7.7 mmHg (range, 4.5-9.1;
      preoperative values) to 2.2 mmHg (range, 0-6.8; early postoperative values) and
      2.3 mmHg (range, 0-3.7) at 8 weeks after surgery (p < 0.001). In addition, the
      length of the lower esophageal sphincter as well as the sphincter pressure vector
      volume were significantly reduced early as well as at 8 weeks after laparoscopic
      myectomy. Furthermore, endoscopy and reflux testing were pathologic compared with
      control animals. CONCLUSIONS: Laparoscopic partial myectomy results in complete
      sphincter insufficiency with only little procedure-related morbidity. This
      procedure allows for the experimental evaluation of surgical procedures on the
      gastroesophageal junction. Future modifications of surgical antireflux procedures
      can therefore be evaluated in an experimental setting prior to their clinical
      introduction.

PMID- 16432651
TI  - A new camera trocar for gasless endoscopic thyroid surgery.
AB  - A commercially available camera trocar diminishes the working space because of
      its high profile and is not proof against blood stain. The authors designed a new
      camera trocar for gasless endoscopic thyroid surgery. The new trocar consists of
      a shaft for a 5-mm endoscope as well as a disc 18 mm in diameter and 2 mm thick.
      The trocar is inserted from an adjacent 3-cm working port, pushed out to an
      incision for a 5-mm endoscope, and placed with the shaft up and the disc down.
      Because of its disc, the trocar is designed to be proof against blood stain and
      to maintain more working space. The newly designed trocar might be very useful
      for gasless endoscopic thyroid surgery as well as other gasless surgical
      procedures.

PMID- 16432653
TI  - A novel approach to bilateral hand-assisted laparoscopic nephrectomy for
      autosomal dominant polycystic kidney disease.
AB  - PURPOSE: Laparoscopic nephrectomy in patients with autosomal dominant polycystic
      kidney disease (ADPKD) is technically challenging. We describe our technique and
      present our experience with a transperitoneal hand-assisted laparoscopic (HAL)
      technique using a standard vacuum curettage system to reduce the size of the
      kidneys thereby facilitating nephrectomy. MATERIALS AND METHODS: A retrospective
      review was completed of 10 consecutive patients undergoing bilateral HAL
      nephrectomy between March 2002 and October 2004 using the following technique. A
      hand port is positioned through a 6-7 cm periumbilical incision and port sites
      are placed at the midclavicular line (12 mm) and anterior axillary line (5 mm) on
      the side of the initial nephrectomy. After the renal vessels are divided and the
      kidney is completely mobilized a 12 mm curette is inserted through the medial
      port site. The Berkeley VC-10 Vacuum Curettage System (ACMI, Southborough, MA) is
      used to morcellate and aspirate the kidney providing a significant decrease in
      the overall size and allowing easy extraction through the midline incision. The
      procedure is repeated for the contralateral side. RESULTS: All 10 patients
      underwent successful bilateral HAL nephrectomy with a mean operative time of 194
      minutes. The average length of stay was 4.7 days. Patients with renal allografts
      had stable function at the time of discharge. The average size of the kidneys
      removed was 717 g and average length was 19 cm. All patients did well
      postoperatively with complete resolution of their presenting symptoms.
      CONCLUSION: In patients with symptomatic ADPKD, bilateral HAL nephrectomy using
      the vacuum curettage system to minimize the size of the kidneys is fast, safe and
      effective.

PMID- 16432652
TI  - Transgastric endoscopic splenectomy: is it possible?
AB  - BACKGROUND: We have previously reported the feasibility of diagnostic and
      therapeutic peritoneoscopy including liver biopsy, gastrojejunostomy, and tubal
      ligation by an oral transgastric approach. We present results of per-oral
      transgastric splenectomy in a porcine model. The goal of this study was to
      determine the technical feasibility of per-oral transgastric splenectomy using a
      flexible endoscope. METHODS: We performed acute experiments on 50-kg pigs. All
      animals were fed liquids for 3 days prior to procedure. The procedures were
      performed under general anesthesia with endotracheal intubation. The flexible
      endoscope was passed per orally into the stomach and puncture of the gastric wall
      was performed with a needle knife. The puncture was extended to create a 1.5-cm
      incision using a pull-type sphincterotome, and a double-channel endoscope was
      advanced into the peritoneal cavity. The peritoneal cavity was insufflated with
      air through the endoscope. The spleen was visualized. The splenic vessels were
      ligated with endoscopic loops and clips, and then mesentery was dissected using
      electrocautery. RESULTS: Endoscopic splenectomy was performed on six pigs. There
      were no complications during gastric incision and entrance into the peritoneal
      cavity. Visualization of the spleen and other intraperitoneal organs was very
      good. Ligation of the splenic vessels and mobilization of the spleen were
      achieved using commercially available devices and endoscopic accessories.
      CONCLUSIONS: Transgastric endoscopic splenectomy in a porcine model appears
      technically feasible. Additional long-term survival experiments are planned.

PMID- 16432655
TI  - Usefulness of a virtual reality simulator or training box for endoscopic surgery
      training.
AB  - This study investigated whether the use of a simulator for endoscopic surgery
      training improves the performance of actual operations. For the study, 16 medical
      students were divided into three groups: a virtual reality (VR) simulator group
      (n = 6), a training box (TB) group (n = 6), and a control group (n = 4). The VR
      and TB groups received 2 h of training per day for 5 days, after which they were
      requested to perform intestinal dissection, to close a gastric perforation, and
      to perform cholecystectomy in pigs. Performance was assessed on the basis of the
      operating time and the error score. Although there were no differences between
      the three groups in terms of the total operating time or error score, the VR and
      TB groups required less time for closure of the gastric perforation than the
      control group. In addition, the operating time decreased as actual operating
      experience increased in the VR group. In the TB group, the time for closure of a
      gastric perforation was shorter when the supervisor had seen the operation before
      training. These findings demonstrated that a simulator is useful for acquiring
      psychomotor skills, but does not immediately enable clinical performance of an
      operation. More actual experience and good supervision are essential for
      increasing the effectiveness of training with the VR and TB simulators,
      respectively.

PMID- 16432654
TI  - Altered plasma matrix metalloproteinase-9/tissue inhibitor of matrix [corrected]
      metalloproteinase-1 concentration during the early postoperative period in
      patients with colorectal cancer.
AB  - BACKGROUND: The authors have previously demonstrated that insulin-like growth
      factor binding protein-3 (IGFBP-3) is depleted in plasma for 1 to 3 days after
      major open surgery (OS), but not after laparoscopic surgery (LS). After surgery,
      IGFP-3 cleavage occurs rapidly and is likely attributable to altered plasma
      proteolytic activity. This study aimed to assess plasma proteolysis after both
      open and closed colorectal resection and, if possible, to identify a
      protease/protease inhibitor system affected by surgery. METHODS: Plasma from 88
      patients with colorectal cancer (stages I-III) who underwent resection was
      obtained preoperatively (pre-OP) and on postoperative days (POD) 1 to 3. Plasma
      proteolytic activity was assessed via zymography. On the basis of the results,
      specific protease and protease inhibitor concentrations were next measured via
      enzyme-linked immunoassay (ELISA). Statistical analysis was performed using
      Wilcoxon's test. RESULTS: Early after surgery, zymography showed a predominant
      band representing a 92-kDa gelatinase corresponding to a proform of matrix
      metalloproteinase-9 (MMP-9), a protease known to cleave IGFBP-3. In OS patients,
      the mean concentration of plasma MMP-9 was significantly higher on POD 1 than at
      pre-OP (p < 0.003). On POD 2 and 3, no differences were noted. In the LS group,
      the mean levels of MMP-9 before and after surgery were comparable. The levels of
      a natural MMP-9 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), also
      were measured. In the OS group, the level of TIMP-1 was significantly higher on
      POD 1 (p < 0.0003) and POD 2 (p < 0.01) and 3 (p < 0.01) than at pre-OP. In the
      LS group, a smaller but significant increase in TIMP-1 levels was found between
      the pre-OP sample and the POD 1 (p < 0.01) and POD 2 (p < 0.01) samples. No
      difference was noted on POD 3 (p = 0.1). CONCLUSIONS: Open surgery, but not
      laparoscopic surgery, is accompanied by a short-lived significant increase in MMP
      9 levels, which likely accounts for the decrease in IGFBP-3 levels observed after
      OS. The transitory nature of MMP-9 imbalance may be attributable to the increase
      in TIMP-1 levels postoperatively.

PMID- 16432656
TI  - A lightweight polypropylene mesh (TiMesh) for laparoscopic intraperitoneal repair
      of abdominal wall hernias: comparison of biocompatibility with the DualMesh in an
      experimental study using the porcine model.
AB  - BACKGROUND: Despite numerous experimental studies, conducted most often with the
      open small-animal model, the ideal structure for a mesh with maximum
      biocompatibility in the intraabdominal region has yet to be found. To date, few
      experimental models have been concerned with the laparoscopic intraabdominal
      implantation of meshes. Numerous experimental and clinical studies appear to have
      identified expanded polytetrafluoroethylene (ePTFE), in the form of DualMesh, as
      the gold standard. Since publications have reported fistula formation and marked
      adhesions to be associated with the use of polypropylene meshes, only few studies
      have investigated meshes made of this material. It is known, however, that a
      reduction in the amount of material and an increase in pore size results in
      better mesh biocompatibility. METHODS: Six pigs each underwent laparoscopic
      intraabdominal placement of either a TiMesh or a DualMesh, both of which were
      prepared for implantation in standardized fashion. After 87 +/- 2 days, the pigs
      were killed, and postmortem laparoscopy was performed, followed by the removal of
      the tissue embedding the mesh for assessment of adhesions and shrinkage, and for
      histologic workup. The specimens were processed both histologically and
      immunohistochemically. RESULTS: In all but one case, the greater omentum adhered,
      usually over discrete areas, to the mesh. In every case the omentum was separable
      from the mesh surface only by sharp dissection. With the titanium-coated
      polypropylene meshes, the average total adhesion area was only 0.085, as compared
      with 0.25 for the GoreTex meshes (p = 0.055). The GoreTex meshes showed an
      average shrinkage to almost half of the original surface area (median, 0.435).
      The average shrinkage of the TiMesh, was to 0.18 of the original area (p =
      0.006), which thus was significantly smaller. Determination of the partial volume
      of the inflammatory cells showed significantly lower median figures for the
      TiMesh (p = 0.009). Measurements of the proliferation marker Ki67 showed
      significantly higher values for ePTFE than for TiMesh (p = 0.011). The apoptosis
      index was significantly higher for the ePTFE membranes (p = 0.002). CONCLUSIONS:
      Titanium-coated polypropylene mesh (TiMesh) is clearly superior to the DualMesh
      in terms of biocompatibility, and is thus suitable for the laparoscopic
      intraperitoneal repair of abdominal wall and incisional hernias.

PMID- 16432657
TI  - Multimodal therapy of anal cancer added by new endosonographic-guided
      brachytherapy.
AB  - BACKGROUND: The most appropriate therapy for anal cancer is external beam
      radiotherapy (EBRT) combined with chemotherapy (CTX). The significance of
      additional brachytherapy is still under evaluation. We report on our experience
      of combined modality therapy of anal cancer and transrectal ultrasound (TRUS)
      guided high-dose rate (HDR) afterloading therapy, referring to results of a study
      published in 1998 by the coauthors. METHODS: From 1993 to 2001, 50 patients with
      anal cancer were treated. After combined RCTX, HDR 2 x 4 Gy brachytherapy was
      administered based on TRUS imaging as a target. RESULTS: In five patients (10%),
      tumor recurrence occurred or the tumor did not respond to therapy, and four (8%)
      developed distant lymph nodes or organ metastases. Five patients (10%) had to
      undergo salvage abdominoperineal resection because of suspected recurrence.
      Specific disease-related 5-year survival was 82%. Therapy-associated
      complications in terms of sphincter necrosis and incontinence were observed in
      three patients (6%). CONCLUSIONS: TRUS-guided brachytherapy permits excellent
      local tumor control and results in minimal treatment-related morbidity.
      Consequently, TRUS-guided brachytherapy may be a useful addition to current
      combined modality treatment regimens for anal cancer.

PMID- 16432658
TI  - Laparoscopic surgery in children is associated with an intraoperative
      hypermetabolic response.
AB  - BACKGROUND: Laparoscopic surgery is thought to be associated with a reduced
      metabolic response compared to open surgery. Oxygen consumption (VO2) and energy
      metabolism during laparoscopic surgery have not been characterized in children.
      METHODS: We measured respiratory gas exchange intraoperatively in children
      undergoing 19 open and 20 laparoscopic procedures. Premature infants and patients
      with metabolic, renal, and cardiac abnormalities were excluded. Anesthesia was
      standardized. Unheated carbon dioxide was used for insufflation. VO2 was measured
      by indirect calorimetry. Core temperature was measured using an esophageal
      temperature probe. RESULTS: We found a steady increase in VO2 during laparoscopy.
      The increase in VO2 was more marked in younger children and was associated with a
      significant rise in core temperature. Open surgery was not associated with
      significant changes in core temperature or VO2. CONCLUSIONS: Laparoscopy in
      children is associated with an intraoperative hypermetabolic response
      characterized by increased oxygen consumption and core temperature. These changes
      are more marked in younger children.

PMID- 16432659
TI  - Laparoscopic hiatal hernia repair: long-term outcome with the focus on the
      influence of mesh reinforcement.
AB  - BACKGROUND: The recurrence rate after laparoscopic repair of hiatal hernias with
      paraesophageal involvement (LRHP) is reported to be high. Mesh reinforcement has
      been proposed with the objective of solving this problem. This study aimed to
      compare the outcome of LRHP before and after the introduction of mesh
      reinforcement. METHODS: Between 1992 and 2003, 56 consecutive patients received
      LRHP including posterior crurorrhaphy and additional fundoplication. Of these 56
      patients, 17 underwent a mesh-reinforced hiatoplasty. Perioperative outcome was
      assessed retrospectively, and follow-up assessment was performed according to
      protocol including a barium contrast swallow. RESULTS: The follow-up period
      averaged 52 +/- 31 months (range, 9-117 months). The recurrence rate for hiatal
      hernia without mesh reinforcement was 19% (7/36). No recurrence (0/16) was
      observed in patients with mesh reinforcement. The intraoperative complication
      rate was 9%, and the perioperative morbidity rate was 14%. There were neither
      mesh-related complications nor operation-related deaths. CONCLUSIONS: Although
      challenging, LRPH is a successful procedure. The high recurrence rate reported in
      the literature can be reduced by additional mesh reinforcement.

PMID- 16432660
TI  - Is the laparoscopic Palomo procedure for pediatric varicocele safe and effective?
      Nine years of unicentric experience.
AB  - BACKGROUND: Varicocele is a rare disorder in children that can lead to testicular
      atrophy and infertility; therefore, radical treatment is frequently required.
      Whatever treatment is chosen, postoperative complications are fairly common
      (hydrocele, recurrence, persistence, and testicular atrophy). Laparoscopic
      varicocelectomy (the laparoscopic Palomo procedure) is one of the surgical
      options that has recently gained popularity. The aim of this study is to assess
      the safety and effectiveness of laparoscopic Palomo varicocelectomy by describing
      a series of patients operated on during a 9 year period at the Royal Hospital for
      Sick Children in Edinburgh. METHODS: This is a retrospective unicentric study
      including patients operated on between June 1995 and June 2004. All patients
      preoperatively underwent ultrasound scan of the testicles (color Doppler) and the
      abdomen. Indications for surgery included symptoms, high-grade varicocele (grade
      II and III), and testicular atrophy. Pneumoperitoneum was created using carbon
      dioxide insufflation with intraabdominal pressure up to 12 mmHg. Three 5 mm ports
      were inserted. The first port was inserted just below the umbilicus (telescope)
      under direct vision, and the others were inserted at the left flank and in the
      suprapubic region. All the enlarged spermatic and vas vessels were ligated or
      clipped. Outcomes and possible intraoperative, postoperative, or long-term
      complications are described. RESULTS: Forty-one patients were included in the
      study. Ninety percent of symptomatic patients improved significantly
      postoperatively, and 62% of patients with preoperative testicular atrophy showed
      postoperative catch-up growth of the involved testis. Nevertheless, hydrocele
      represents the most frequent postoperative complication in this series of
      patients. Approximately 15% of the patients required some sort of further
      surgical intervention (12% because of postoperative hydrocele occurrence).
      CONCLUSIONS: The laparoscopic Palomo procedure is a safe and effective surgical
      option for the treatment of pediatric varicocele, although it carries a fairly
      high risk of postoperative hydrocele. Postoperative hydrocele seems to be related
      to some sort of lymphatic obstruction, therefore lymphatic sparing procedures
      that can be accomplished laparoscopically should be reconsidered. Nevertheless,
      their feasibility and effectiveness need to be more carefully assessed.

PMID- 16432663
TI  - The circadian clock in mammals.
AB  - The basic physiological and anatomical basis for circadian rhythms in mammalian
      behaviour and physiology is introduced. The pathways involved in photic
      entrainment of the circadian clock are discussed in relation of new findings that
      identify the molecules that are involved in signalling between the environment
      and the clock. The molecular basis of endogenous cycles is described in the
      mouse, and compared to the mechanism that is present in the fly. Finally we
      speculate on the relationship between circadian physiology and pain.

PMID- 16432661
TI  - Peripheral blood lymphocyte apoptosis and circulating dendritic cells in patients
      with systemic lupus erythematosus: correlation with immunological status and
      disease-related symptoms.
AB  - We investigated in vivo the relationship between the degree of peripheral blood
      lymphocyte apoptosis and circulating dendritic cells (DC) as well as the
      immunological status in 45 patients with systemic lupus erythematous (SLE).
      Apoptosis was detected by phosphatidylserine externalization and assays to detect
      caspase activation. The total DC count (tDC) and their myeloid, mDC1 (BDCA1+) and
      mDC2 (BDCA3+), and plasmacytoid, pDC (BDCA3+), subtypes were assessed. Moreover,
      several immunological parameters, such as complement proteins, interferons (IFN),
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-6 levels were
      assessed. There were no significant differences in both the intensity of
      apoptosis and DC counts between active and inactive SLE as well as between
      untreated patients and those treated with steroids. The incidence of lymphocyte
      apoptosis correlated positively with T-cell count, both T-helper (p=0.004) and
      cytotoxic T cells (p=0.001), but not with B or natural killer (NK) cells. The
      intensity of apoptosis enhanced along with the increase in complement C3
      (p=0.016) and decrease in IFN-gamma (p=0.040) levels. The apoptotic cell count
      correlated with tDC (p=0.031), mDC1 (p=0.007), and pDC (p=0.039) counts. Both tDC
      and mDC1 counts correlated positively with antinuclear antibody (ANA) titers
      (p=0.017 and 0.032, respectively). Moreover, tDC correlated with C4 (p=0.039) and
      pDC with both C3 (p=0.032) and C4 (p=0.007) levels. The DC counts correlated
      inversely with IFN-gamma (tDC, p=0.038; mDC1, p=0.009), IL-6 (mDC2, p=0.031), or
      serum IgG levels (tDC, p=0.006; mDC1, p<0.001; mDC2, p=0.001). We found a
      positive correlation between lymphocyte apoptosis and peripheral blood DC count
      as well as the level of complement proteins in patients with SLE. The enhanced
      lymphocyte apoptosis was accompanied by the decrease in concentration of some
      cytokines, such as IFN-gamma or IL-6, as well as serum IgG level. This finding
      may reflect pathogenetic events during development of the disease, which include
      a persistent signal derived from circulating apoptotic lymphocytes, mobilizing
      the complement system, and attracting peripheral blood DC.

PMID- 16432662
TI  - The supramolecular structure of milk fat influences plasma triacylglycerols and
      fatty acid profile in the rat.
AB  - BACKGROUND: The digestion fate of milk fat depending on its supramolecular
      structure for a given dairy product composition has rarely been studied. AIM OF
      THE STUDY: To highlight differences of lipid digestion, we measured (i) the
      plasma triacylglycerol and cholesterol concentrations and (ii) the total plasma
      fatty acid profile of fasted rats force-fed with different dairy preparations;
      the three creams and the unemulsified preparation had a similar composition with
      different and controlled fat suprastructures. METHODS: All preparations,
      manufactured in the laboratory from a given milk batch, contained 205 +/- 3 g .
      kg(-1) fat that was either fed (i) unemulsified consecutively to the skim milk
      phase, or as a cream with the following fat globule structures: (ii) native milk
      fat globules of approximately 4 microm covered with the native milk fat globule
      membrane (MFGM), (iii) small native milk fat globules of approximately 2 microm
      selected from the latter by microfiltration and covered by the MFGM, or (iv) fine
      homogenized fat droplets of approximately 1 microm covered mainly with caseins.
      RESULTS: The plasma triacylglycerol appearance was delayed for the creams
      compared with the rapid onset for the unemulsified preparation. At 90 and 180 min
      after feeding, the plasma triacylglycerol enrichment was significantly lower for
      the homogenized cream than for the unemulsified preparation. At 120 min after
      feeding, triacylglycerol enrichment was significantly lower for each cream than
      for the unemulsified preparation. At 180 min after feeding, the plasma relative
      enrichment in C12, C14, C15, C16 and C18:1 n-9 fatty acids was significantly
      lower for the homogenized cream than for unemulsified fat and regular cream.
      CONCLUSIONS: Global lipid digestion based on plasma triacylglycerol enrichment
      and relative enrichments in some fatty acids was decreased with small homogenized
      milk fat droplets compared to unemulsified milk fat. These data show that dairy
      products with the same composition but varying in fat supramolecular structure
      result in different kinetics of lipid digestion, which could be of health
      concern.

PMID- 16432664
TI  - Differential expression of HER-2/NEU receptor of invasive mammary carcinoma
      between Caucasian and African American patients in the Detroit metropolitan area.
      Correlation with overall survival and other prognostic factors.
AB  - GOALS: HER-2/neu overexpression in invasive mammary carcinoma is associated with
      more aggressive biologic behavior. Breast cancer in African American (AA) women
      has been associated with a shorter survival rate than that seen in Caucasians
      (C). This study evaluated the frequency of HER-2/neu overexpression in C compared
      to AA patients and the association of HER-2/neu expression with overall survival
      and other prognostic factors. METHODS: A retrospective review of the SEER data of
      Karmanos Cancer Institute for patients with invasive mammary carcinoma was
      conducted between 1998 and 2001. Pathology reports and pathology slides were
      obtained for those patients with missing data. Available data and material on 608
      patients were found. The median follow-up interval was 35 months with a range of
      1-91 months. 46.7% of the study population was C while 53.3% was AA. The
      differential of HER-2/neu expression in C and AA was evaluated. The association
      of HER-2/neu expression and other prognostic factors with overall survival was
      carried out by univariate and multivariable analyses using Cox's proportional
      hazards regression model. PRINCIPLE RESULTS: No statistically significant
      difference was found in HER-2/neu expression between C and AA patients.
      Overexpression of HER-2/neu did not correlate with decreased overall survival in
      this analysis. MAJOR CONCLUSIONS: Breast cancer HER-2/neu expression in AA
      patients is not statistically different from that of Caucasians. HER-2/neu
      expression is not associated with overall survival. Among the other prognostic
      factors analyzed, ER status and histologic grade were not statistically
      significant.

PMID- 16432665
TI  - Land plants equilibrate O2 and CO2 concentrations in the atmosphere.
AB  - The role of land plants in establishing our present day atmosphere is analysed.
      Before the evolution of land plants, photosynthesis by marine and fresh water
      organisms was not intensive enough to deplete CO(2) from the atmosphere, the
      concentration of which was more than the order of magnitude higher than present.
      With the appearance of land plants, the exudation of organic acids by roots,
      following respiratory and photorespiratory metabolism, led to phosphate
      weathering from rocks thus increasing aquatic productivity. Weathering also
      replaced silicates by carbonates, thus decreasing the atmospheric CO(2)
      concentration. As a result of both intensive photosynthesis and weathering, CO(2
      )was depleted from the atmosphere down to low values approaching the compensation
      point of land plants. During the same time period, the atmospheric O(2)
      concentration increased to maximum levels about 300 million years ago (Permo
      Carboniferous boundary), establishing an O(2)/CO(2) ratio above 1000. At this
      point, land plant productivity and weathering strongly decreased, exerting
      negative feedback on aquatic productivity. Increased CO(2) concentrations were
      triggered by asteroid impacts and volcanic activity and in the Mesozoic era could
      be related to the gymnosperm flora with lower metabolic and weathering rates. A
      high O(2)/CO(2) ratio is metabolically linked to the formation of citrate and
      oxalate, the main factors causing weathering, and to the production of reactive
      oxygen species, which triggered mutations and stimulated the evolution of land
      plants. The development of angiosperms resulted in a decrease in CO(2)
      concentration during the Cenozoic era, which finally led to the glacial
      interglacial oscillations in the Pleistocene epoch. Photorespiration, the rate of
      which is directly related to the O(2)/CO(2) ratio, due to the dual function of
      Rubisco, may be an important mechanism in maintaining the limits of O(2) and
      CO(2) concentrations by restricting land plant productivity and weathering.

PMID- 16432666
TI  - Kinetic analysis of the slow inactivation of Rubisco during catalysis: effects of
      temperature, O2 and Mg(++).
AB  - The effect of temperature, O(2) and Mg(++) on the kinetic characteristics of the
      slow inactivation (fallover) of Rubisco isolated from spinach (Spinacia oleracea
      L.) was determined. Comparing 25 and 45 degrees C, the rate of activity decline
      of Rubisco increased by 20-fold, but the final ratio of steady state to initial
      activity increased from 0.38 to 0.62, respectively. Low CO(2) increased the
      extent of fallover but only caused a marginal increase in fallover rate in
      agreement with results reported previously. In contrast, increased O(2) during
      catalysis significantly increased only the fallover rate. Low Mg(++) greatly
      increased the fallover of Rubisco both in rate and extent. Rubisco carbamylation
      was assayed using a new separation technique and it revealed that a loss of
      carbamylation largely accounted for the increased fallover observed with low
      Mg(++). In conclusion, Rubisco fallover is facilitated by high temperature, low
      concentration of CO(2) or Mg(++), and high O(2). The physiological importance of
      these factors in affecting Rubisco fallover and contributing to photosynthetic
      inhibition at high temperatures in planta are discussed.

PMID- 16432667
TI  - Driving multi-electron reactions with photons: dinuclear ruthenium complexes
      capable of stepwise and concerted multi-electron reduction.
AB  - Using biological precedents, it is expected that concerted, multi-electron
      reduction processes will play a significant role in the development of efficient
      artificial photosynthetic systems. We have found that the dinuclear ruthenium
      complexes [(phen)(2)Ru(tatpp)Ru(phen)(2)](4+) (P) and [(phen)(2)Ru(tatpq)
      Ru(phen)(2)](4+) (Q) undergo photodriven 2- and 4-electron reductions,
      respectively, in the presence of a sacrificial reductant. Importantly, these
      processes are completely reversible upon exposure to air, and consequently, these
      complexes have the potential to be used catalytically in multi-electron transfer
      reactions. A localized molecular orbital description of the ligands and complexes
      is used to explain both the function and spectroscopy of these complexes. In both
      complexes, the reducing equivalents are stored in the pi* orbitals of the
      bridging ligands and depending on the solution pH, various protonation states of
      the reduced species of P and Q are obtained. Under basic conditions, the
      photochemical pathway favors sequential single-electron reductions, while neutral
      or slightly acidic conditions give rise to proton-coupled multi-electron
      transfer. In fact, at sufficiently acidic pH, only a coupled two-electron, 2
      proton process is seen. Few molecular photocatalysts are capable of proton
      coupled multi-electron transfer, which is believed to be a fundamental component
      of light-activated energy storage in nature.

PMID- 16432668
TI  - Obstetric admissions to the intensive care unit: a 12-year review.
AB  - OBJECTIVE: The objective was to ascertain the prevalence, causes and outcome of
      critically ill obstetric patients admitted to the intensive care unit (ICU).
      DESIGN: The design was a retrospective collection of data. SETTINGS: The setting
      was a multidisciplinary ICU in a University hospital. PATIENTS: All obstetric
      patients admitted to the ICU over a 12-year period from May 1992 to April 2004
      were reviewed. METHODS: Data collected included demographic characteristics of
      the patients, pre-existing medical conditions, obstetric complications, invasive
      procedures required in the ICU and outcome of the patients. RESULTS: The
      incidence of obstetric admissions to the ICU represented 0.22% of all deliveries
      during the study period. The majority (84.4%) of patients were admitted to the
      ICU postpartum. Obstetric haemorrhage (32.8%) and pregnancy-induced hypertension
      (17.2%) were the two main obstetrical reasons for admission. The remainder
      included medical disorders (37.5%) and other causes (6.2%). Associated major
      complications included adult respiratory distress syndrome (ARDS) and HELLP
      (haemolysis, elevated liver enzymes and low platelets) syndrome. The perinatal
      mortality rate was 20% and the maternal mortality rate 9.4%. CONCLUSIONS: A team
      approach consisting treatment by obstetricians, intensive care specialists and
      anaesthesiologists provided optimal care for the patients. Improved management
      strategies for obstetric haemorrhage and hypertension may significantly reduce
      maternal morbidity.

PMID- 16432669
TI  - Both sides of the story - cerebral infarction after intra-abdominal bleeding.

PMID- 16432670
TI  - Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose.
AB  - OBJECTIVE: The Brugada syndrome is a clinical and electrocardiographic familial
      entity, which may lead to sudden cardiac death. A Brugada pattern ECG may
      occasionally be caused by conditions such as an overdose of tricyclic
      antidepressants (TCA). Toxicity of TCA frequently results in the need for
      critical care support. We retrospectively studied characteristics and
      electrocardiographic indicators of toxicity of all TCA poisoned patients.
      SETTING: All patients admitted from 1/1/2000 to 1/11/2004 to our ICU after an act
      of deliberate self-poisoning were included. The ECG's were analysed
      retrospectively by a cardiologist. Patients with an overdose of TCA were divided
      in three groups; I. without ECG abnormalities, II. Presence of ECG abnormalities
      but without Brugada signs, III patients with a Brugada pattern ECG. RESULTS: 134
      patients were admitted. In 35 patients a TCA was the main toxic substance. In 12
      (34%) TCA patients no ECG abnormalities were found. An increase in QRS duration
      (>100 ms) was seen in 13 (37%) cases. Six (17%) of them demonstrated a Brugada
      like pattern. The ECG abnormalities resolved quickly after administration of
      sodium bicarbonate. Length of stay did not differ between groups. APACHE II and
      the amount of sodium bicarbonate administered were the highest in the Brugada
      pattern group. Two patients died. CONCLUSIONS: in TCA poisoning the Brugada
      pattern ECG is a particular manifestation of the frequently occurring
      intraventricular conduction disturbances. In intoxicated patients in whom the
      substance is unknown early recognition of the conduction disturbances is
      important for suspecting a poisoning with TCA.

PMID- 16432671
TI  - Adrenal-exhaustion syndrome in patients with liver disease.
AB  - OBJECTIVE: Adrenal failure is emerging as an important cause of excess morbidity
      and mortality in critically ill patients. We have recently reported the high
      incidence of adrenal failure in patients with liver disease, the so called
      "hepato-adrenal syndrome." It has been noted that patients who on initial testing
      may have "normal" adrenal function subsequently progress to overt adrenal
      failure, the adrenal-exhaustion syndrome. The goal of this study was to further
      characterize this syndrome. DESIGN: Retrospective review of the "Hepatic Cortisol
      Research and Adrenal Pathophysiology Study" database. SETTING: Liver transplant
      ICU of a tertiary care university hospital. PATIENTS AND METHODS: Patients who on
      initial testing had "normal" adrenal function were followed, and adrenal function
      testing was repeated in those who failed to improve. The patients were grouped as
      follows: (1) patients who developed adrenal failure on follow-up testing; and (2)
      patients who had normal adrenal function during their ICU stay. The incidence and
      risk factors for the development of adrenal-exhaustion syndrome were determined.
      MEASUREMENTS AND RESULTS: The study cohort consisted of 221 patients, of whom 120
      (54%) were diagnosed with adrenal insufficiency on initial diagnostic testing and
      were excluded from further analysis. The remaining 101 patients comprised those
      who made up the group of interest. On follow-up, 16 (16%) of these developed
      adrenal failure a mean of 3 days after initial testing. The only factor that
      predicted the development of adrenal-exhaustion syndrome was a low HDL level
      (p<0.001). CONCLUSION: This study demonstrates that adrenal failure is a dynamic
      process and that repeat adrenal function testing is indicated in patients who
      remain hemodynamically unstable or fail to improve with aggressive supportive
      treatment. Low HDL levels may be pathogenetically linked to the development of
      adrenal failure.

PMID- 16432672
TI  - Adaptive mechanical backup ventilation for preterm infants on respiratory assist
      modes - a pilot study.
AB  - BACKGROUND: Mechanical respiratory-assist modes, such as assist/control, low-rate
      intermittent mandatory ventilation, continuous positive airway pressure, or
      proportional assist ventilation (PAV), require a continuous respiratory effort.
      Because of the frequent occurrence of periodic breathing and/or apnea, mechanical
      backup ventilation must be initiated during episodes of reduced or absent
      respiratory drive to maintain gas exchange. The common approach to this problem
      is a regular conventional mechanical ventilation, which is initiated and
      withdrawn in an "on/off" function. OBJECTIVE: To develop and evaluate a
      mechanical backup ventilation mode that is adaptive to the rapidly changing
      breathing pattern of preterm infants. DESIGN: Prospective randomized clinical
      crossover trial. SETTING: Neonatal intensive care unit at the University of
      Munich, Germany. PATIENTS: Preterm infants undergoing PAV. INTERVENTIONS: The
      infants were ventilated with PAV using a newly developed adaptive backup support,
      with and without pulse-oximetry-guided operation (SpO(2)-sensitive backup). Each
      infant was ventilated with both modes of backup support on 2 consecutive days,
      with the sequence randomized. MEASUREMENTS AND RESULTS: The analysis on 11
      preterm infants showed a statistically significant and clinically relevant
      reduction of the incidence (33%) and duration of oxygen desaturations (52%) when
      SpO(2)-sensitive adaptive backup support was used. CONCLUSIONS: SpO(2)-sensitive
      adaptive backup proved safe and effective in reducing the incidence and duration
      of oxygen desaturation in this short-term trial. This technology is potentially
      applicable to other assisted modalities of ventilation, such as noninvasive nasal
      ventilation.

PMID- 16432673
TI  - Acute liver failure as the first manifestation of severe traumatic tricuspid
      valve insufficiency.

PMID- 16432674
TI  - Ultrasound estimation of volume of pleural fluid in mechanically ventilated
      patients.
AB  - OBJECTIVE: The aim was to develop a practical method for estimation of the volume
      of pleural effusion using ultrasonography in mechanically ventilated patients.
      DESIGN: Prospective observational study. SETTING: 20-bed general intensive care
      unit in the university hospital. PATIENTS AND PARTICIPANTS: 81 patients were
      included after initial suspicion of pleural fluid on chest supine X-ray and pre
      puncture ultrasound confirming effusion. Patients with thoracic deformities, post
      lung surgery, with diaphragm pathology, haemothorax, empyema and with incomplete
      aspiration of pleural fluid on post-puncture ultrasound were excluded.
      INTERVENTIONS: Patients were supine with mild trunk elevation at 15 degrees .
      Probe was moved upwards in posterior axillary line, and transverse section
      perpendicular to the body axis was obtained with pleural separation visible at
      lung base. The maximal distance between parietal and visceral pleura (Sep) in end
      expiration was recorded. Thoracentesis was performed at previous probe position
      and volume of pleural fluid (V) recorded. MEASUREMENTS AND RESULTS: 92 effusions
      were evaluated and drained; 11 (12%) were excluded for incomplete aspiration.
      Success rate of obtaining fluid under ultrasound guidance was 100%; the incidence
      of pneumothorax or bleeding was zero. Mean Sep was 35+/-13 mm. Mean V was 658+/
      320 ml. Significant positive correlation between both Sep and V was found:
      r=0.72; r(2)=0.52; p<0.001. The amount of pleural fluid volume can be estimated
      with the simplified formula: V (ml)=20 x Sep (mm). Mean prediction error of V
      using Sep was 158.4+/-160.6 ml. CONCLUSIONS: Easy quantification of pleural fluid
      may help to decide about performing thoracentesis in high-risk patients, although
      thoracentesis under ultrasound guidance appears to be a safe procedure.

PMID- 16432675
TI  - Air ionisation and colonisation/infection with methicillin-resistant
      Staphylococcus aureus and Acinetobacter species in an intensive care unit.
AB  - OBJECTIVE: To determine effect of negative air ions on colonisation/infection
      with methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter species
      in an intensive care unit. DESIGN: Prospective single-centre cross-over study in
      an adult general intensive care unit. PATIENTS: 201 patients whose stay on the
      unit exceeded 48 hour's duration. INTERVENTION: Six negative air ionisers were
      installed on the unit but not operational for the first 5 months of the study
      (control period). Devices were then operational for the following 5.5 months.
      MEASUREMENTS AND RESULTS: 30 and 13 patients were colonised/infected with MRSA
      and Acinetobacter spp., respectively, over 10.5 months. No change in MRSA
      colonisation/infection was observed compared with the 5 month control period.
      Acinetobacter cases were reduced from 11 to 2 (p=0.007). CONCLUSION: Ionisers may
      have a role in the prevention of Acinetobacter infections.

PMID- 16432676
TI  - Ventricular unloading with a miniature axial flow pump in combination with
      extracorporeal membrane oxygenation.
AB  - OBJECTIVE: ECMO for acute cardiorespiratory failure is an established therapeutic
      option. Persistent insufficient unloading of the left ventricle (LV) can
      compromise recovery of ventricular function. We decided to insert a miniature
      rotary blood pump (Impella) for decompression of the LV. In contrast to previous
      experience with this new device, where it was generally used for postcardiotomy
      heart failure or cardiogenic shock and inserted in the operating room or the
      catheter laboratory, this is the first report describing the potential of this
      technology in the intensive care unit, in a patient on ECMO and the value of
      echocardiography guidance. PATIENT: A 13-year-old boy with a history of
      congenital heart disease was admitted to the ICU with acute cardio-respiratory
      failure. INTERVENTIONS: On day 2 venoarterial ECMO was instituted because of
      worsening cardiorespiratory insufficiency refractory to conventional treatment.
      On day 5 a percutaneous rotary blood pump was inserted to decompress the LV.
      CONCLUSIONS: A percutaneous miniature rotary blood pump can be an alternative to
      decompress a failing LV in the setting of VA-ECMO. Echocardiography can avoid the
      use of fluoroscopy and the transport to a catheter laboratory to insert the
      rotary pump.

PMID- 16432677
TI  - Levels of vancomycin in the cerebral interstitial fluid after severe head injury.
AB  - OBJECTIVE: To evaluate the concentrations of vancomycin in the cerebral
      interstitial fluid after intravenous administration by multiple boli. DESIGN:
      Prospective non randomized study SETTING: University hospital general ICU.
      PATIENTS: Four patients undergone to craniotomy for evacuation of cerebral
      posttraumatic hemorrhage, who developed pneumonia 4-7 days from the injury
      METHODS: Two microdialysis catheters were placed in each patient: one in the
      edematous brain surrounding the focal lesion and one in the subcutaneous tissue
      of abdomen. Levels of vancomycin were measured in serum and in the
      microdialysates samples. RESULTS: Plasmatic concentration of 10-15 microg/ml in
      the trough level was obtained after four administrations of vancomycin. Levels of
      vancomycin in the subcutaneous tissue was above minimum inhibitory concentrations
      in all patients after the second administration. Mean serum/brain ratio was 8%.
      Cerebral interstitial concentration of vancomycin was never above minimum
      inhibitory concentrations; its maximum value was 1.2 microg/ml. CONCLUSIONS: In
      edematous brain close to a posttraumatic hemorrhage the levels of vancomycin do
      not differ from that in healthy subjects. At these plasmatic concentrations
      cerebral interstitial levels of vancomycin were insufficient while subcutaneous
      interstitial levels were effective for clinical use.

PMID- 16432678
TI  - Acute effects of hyperoxemia on dyspnoea and respiratory variables during
      pressure support ventilation.
AB  - OBJECTIVE: To evaluate the acute effect of hyperoxemia on the comfort and the
      respiratory variables in patients undergoing pressure support ventilation (PSV)
      for acute respiratory failure (ARF). DESIGN AND SETTING: Prospective,
      observational study performed in the intensive care unit of a university
      hospital. PATIENTS: Thirteen semirecumbent patients were ventilated in PSV mode,
      the setting of which was established by the treating physician who was blinded to
      the study. MEASUREMENTS: The variables measured at different levels (21-80%) of
      FiO(2) randomly applied were: minute volume (V (E)), respiratory frequency (f)
      and the pressure develing during the first 100 ms of an occluded breath (P(0.1)).
      These variables were firstly measured at the level of FiO(2) chosen by the
      treating physician. Severity of dyspnea was rated using the visual analogue scale
      15' after each FiO(2) variation. RESULTS: Modulation of FiO(2) was able to vary
      significantly the respiratory variables, since a FiO(2) increase was associated
      with a decrease in dyspnea, P(0.1), f, and V (E). While valuable variations were
      detected at both lower and higher values of FiO(2) than those established by the
      treating physician, a significant improvement in the respiratory variables was
      detected at FiO(2) 60%. The reduction in respiratory drive was statistically
      related to an amelioration of dyspnea (R(2)=0.89) even at values of FiO(2) higher
      than 60%. CONCLUSIONS: During PSV the respiratory drive can be heavily modulated
      by varying the FiO(2) since even at FiO(2) greater than 0.6 dyspnea and
      respiratory variables continued to improve.

PMID- 16432679
TI  - Protected telescopic catheter also allows anaerobic bacteria isolation in
      patients with ventilatory-acquired pneumonia.
AB  - OBJECTIVE: To analyze the possibility of isolating anaerobic bacteria using
      protected telescopic catheter (PTC) in patients with ventilatory-associated
      pneumonia. DESIGN AND SETTING: A prospective epidemiological study in a 12-bed
      intensive care unit. PATIENTS: 104 patients with suspected ventilatory-associated
      pneumonia undergoing PTC for microbiological determination including specific
      methods for anaerobic bacteria identification (mean age 59.3, range 17-82; SAPS
      II 44.6+/-17.9). MEASUREMENTS AND RESULTS: We performed 156 PTC procedures. Of
      the 14 cases ventilatory-associated pneumonia occurred early in 6 and in 8 late.
      In 52 samples at least one bacteria was isolated (33.3%). Of the 156 samples 14
      yielded with anaerobic bacteria, representing 26.9% of the positive samples and
      9% of all the samples. CONCLUSION: Considering the potential pathogenic role of
      anaerobic bacteria in patients with ventilatory-associated pneumonia, the
      possibility of isolating these bacteria using PTC and taking into account its
      easiness and limited side effects should be underlined.

PMID- 16432680
TI  - Organ donations and unused potential donations in traumatic brain injury,
      subarachnoid haemorrhage and intracerebral haemorrhage.
AB  - OBJECTIVE: To obtain insight into the occurrence of brain death and the potential
      for brain dead and controlled non-heart-beating organ donors (CNHB) in patients
      with traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) and
      intracerebral haemorrhage (ICH) in a large neurosurgical serving area (2.1
      million inhabitants). DESIGN: Retrospective analysis of data concerning patients
      with TBI, SAH and ICH who died during the course of ICU treatment during 1999
      2003. SETTING: A 16-bed neuro-intensive care unit. PATIENTS: Patients with TBI,
      SAH or ICH who died during the course of ICU treatment. MEASUREMENTS AND RESULTS:
      The number of ICU deaths in patients with TBI, SAH and ICH declined from 111 in
      1999 to 64 in 2003. In total, 476 deaths occurred. Of these, 177 patients were
      not included in the analysis. Two hundred ninety-nine (299) ventilated patients
      had two or more absent brainstem reflexes (ABSR) and a Glasgow Coma Score of 3-4
      at the moment of treatment withdrawal and formed the potential for organ
      donation; 61 of these patients were treated until full brain death. Organs of 57
      patients could be harvested. We analysed the reasons that organs were not
      procured in the 242 remaining patients. The most important reasons were family
      refusal (32%), medical contraindications (14%), and the treating physician not
      considering potential organ donation (20%). The missed potential is 162/299
      (54%). CONCLUSIONS: The number of actual and potential organ donors is declining,
      but a considerable number of potential CNHB donors exists. Refusal by relatives
      is the most important reason for failure to procure organs.

PMID- 16432681
TI  - Effects of topiramate in combination with intravenous nicotine in overnight
      abstinent smokers.
AB  - RATIONALE: Topiramate, an anticonvulsant medication, may be effective as a
      treatment for alcohol and cocaine addiction. While a recent clinical study has
      demonstrated the potential utility of topiramate for smoking cessation in alcohol
      dependent smokers, the effects of topiramate on tobacco addiction have not been
      systematically examined in humans. OBJECTIVES: To determine topiramate's effects
      on acute physiological and subjective responses to intravenous (IV) nicotine in
      overnight abstinent smokers. METHODS: Seven male and five female smokers
      participated in a double-blind, placebo-controlled, crossover study, which
      consisted of one adaptation and three experimental sessions. Before each session,
      participants were treated orally with either a single 25 or 50 mg topiramate dose
      or with placebo. Starting 2 h following the medication treatment, participants
      received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV nicotine.
      RESULTS: Topiramate treatment at 50 mg, compared to 25 mg or placebo, attenuated
      heart rate increases induced by nicotine. Topiramate, compared to placebo,
      enhanced the ratings of subjective effects from nicotine including "drug
      strength," "good effects," "head rush," and "drug liking." Topiramate treatment
      did not affect performance on the Stroop test. CONCLUSIONS: These results suggest
      that topiramate may enhance the subjective effects of nicotine and attenuate the
      heart rate response to nicotine. While the exact mechanisms are unclear,
      enhancement of the dopaminergic system and attenuation of the noradrenergic
      system may mediate the topiramate's effects on the subjective and cardiovascular
      responses to nicotine, respectively. The utility of topiramate for smoking
      cessation needs to be examined further in controlled clinical trials.

PMID- 16432682
TI  - The atypical antipsychotics olanzapine and quetiapine, but not haloperidol,
      reduce ACTH and cortisol secretion in healthy subjects.
AB  - RATIONALE: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis is
      an important aspect of the pathophysiology of major depression and schizophrenia.
      Despite the usefulness of atypical antipsychotics in the treatment of depression
      and their positive influence on cognitive functioning possibly related to their
      impact on cortisol, little is known about their effect on HPA axis function.
      OBJECTIVE: Therefore, this double-blind, placebo-controlled, randomized cross
      over study investigated the influence of the atypical antipsychotics quetiapine
      and olanzapine in comparison with haloperidol and placebo on plasma
      adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels. Eleven
      healthy male volunteers were studied during four sessions one week apart, orally
      receiving placebo, quetiapine (50 mg), olanzapine (5 mg), or haloperidol (3 mg).
      Blood samples were taken at hourly intervals from 0900 until 1700 hours. For
      ACTH, cortisol, and prolactin a significant effect of treatment condition (p < or
      = 0.005; p < or = 0.035; p < or = 0.0001, respectively) for area under the curve
      (AUC) was found. In comparison to placebo, quetiapine and olanzapine
      significantly reduced ACTH (p < or = 0.002; p < or = 0.05, respectively) and
      cortisol (p < or = 0.005; p < or = 0.03, respectively). No effect of haloperidol
      on AUC of ACTH or cortisol levels was observed. In comparison with placebo,
      haloperidol (p < or = 0.0001) and olanzapine (p < or = 0.0001) elevated AUC of
      prolactin plasma levels, whereas no significant effect was observed for
      quetiapine as a main effect of treatment condition. The atypical antipsychotics'
      strong influence on HPA-function with pronounced ACTH and cortisol lowering is
      possibly related to the atypicals' blockade of serotonergic receptors, but
      blockade of adrenergic or histaminergic receptors may play a role as well. The
      observed HPA-axis down-regulation may be clinically important for the atypicals'
      effects on depressive symptomatology and cognitive functioning.

PMID- 16432683
TI  - Potentiating effect of tramadol on methamphetamine-induced behavioral
      sensitization in mice.
AB  - RATIONALE: Polydrug abuse is a common phenomenon in human drug addicts. Previous
      studies have shown that both tramadol (TRAM) and methamphetamine (METH) share the
      ability to modulate brain monoaminergic (dopamine, 5-hydroxytryptamine, and
      noradrenaline) systems that may be involved in behavioral sensitization to METH.
      Therefore, we hypothesized that there would be an interaction between TRAM and
      METH on behavioral sensitization induced by METH. OBJECTIVES: To investigate
      whether TRAM affects METH-induced behavioral sensitization. METHODS: Male Kunming
      mice were subjected to two regimens of drugs: (1) Mice were injected with TRAM (1
      16 mg/kg, i.p.) alone or a combination of TRAM and METH (1 mg/kg, i.p.) once
      daily for 7 days. After 7 drug-free days (on day 15), animals were challenged
      with the corresponding TRAM dose or METH (1 mg/kg, i.p.). On days 1, 7, and 15,
      locomotion was monitored in the open field test after the last injection. (2)
      Mice received METH (1 mg/kg, i.p.) once daily for 7 days, followed by 7 drug-free
      days. On day 15, a challenge of TRAM (1-16 mg/kg, i.p.) or TRAM plus METH (1
      mg/kg, i.p.) was given and then locomotor activity was quantified. RESULTS: TRAM
      or METH challenge did not induce hyperlocomotion in mice chronically treated with
      TRAM, and TRAM challenge was insufficient to induce subsequent hyperlocomotion in
      METH-sensitized mice. However, TRAM significantly increased METH-induced
      hyperlocomotion. TRAM plus METH-sensitized mice showed a significantly greater
      hyperlocomotor response to METH challenge than METH-sensitized mice. Furthermore,
      TRAM (16 mg/kg, i.p.) plus METH (1 mg/kg, i.p.) challenge enhanced the sensitized
      locomotor response compared to METH-alone (1 mg/kg, i.p.) challenge in METH
      sensitized mice. CONCLUSIONS: TRAM fails to produce behavioral sensitization, and
      there is no apparent cross-sensitization between TRAM and METH. However, TRAM can
      increase METH-induced hyperlocomotion and potentiate the development and
      expression of behavioral sensitization to METH.

PMID- 16432685
TI  - Assessment of a case-based training system (d3web.Train) in rheumatology.
AB  - To improve the learning experiences for third year medical students, a case-based
      training program based on real patient records has been introduced as a
      supplement to lectures. It was built with the novel training environment
      d3web.Train. Optimization of the learning environment d3web.Train for both
      teachers and learners has been considered as equally important and offers several
      trade-offs. The training program has been evaluated during three subsequent
      rheumatology courses, the first one voluntary and the latter two mandatory. For
      each course, we tracked how often and intensive each student used the system. In
      addition, the students answered questionnaires about their expectations and
      experiences. In the first voluntary course, 39/92 students finished at least one
      case and solved 187 cases in total (average: 4.8 cases from 12 cases available).
      In the second and third mandatory courses, all students (60 resp. 56) finished at
      least the required 20 cases with an average usage of 22.5 resp. 29.3 out of 31
      available cases. Most of the cases were processed twice by the students in
      preparation for the final examinations. A positive correlation between processed
      cases per student and the exam score could be shown (30, 73 and 95% in the first,
      second and third courses, respectively). The findings clearly exceeded the
      expectations of the students concerning its usefulness as a supplement to
      lectures and as good preparation for their job as physician, as well as the
      learning period to use the program. For working through one case, students needed
      about 9 min on average. The case-based training system d3web.Train offers a new
      tool for medical education in rheumatology. The main advantage of the system is
      the relatively low effort needed to create a case-based program starting from the
      available dismissal records.

PMID- 16432684
TI  - Fluoxetine and norfluoxetine stereospecifically and selectively increase brain
      neurosteroid content at doses that are inactive on 5-HT reuptake.
AB  - It has recently become more clearly understood that in human brain
      pathophysiology, neurosteroids play a role in anxiety disorders, premenstrual
      syndrome, postpartum depression, posttraumatic stress disorder, and depression.
      In the treatment of major depression, recent clinical studies indicate that the
      pharmacological profiles of fluoxetine and fluvoxamine are correlated with the
      ability of these drugs to increase the brain and cerebrospinal fluid content of
      allopregnanolone (Allo), a potent positive allosteric modulator of gamma
      aminobutyric acid (GABA) action at GABAA receptors. Thus, the neurosteroid
      induced positive allosteric modulation of GABA action at GABAA receptors is
      facilitated by fluoxetine or its congeners (i.e., paroxetine, fluvoxamine,
      sertraline), which may not block 5-HT reuptake at the doses currently prescribed
      in the clinic. However, these doses are effective in the treatment of
      premenstrual dysphoria, anxiety, and depression. In socially isolated mice, we
      tested the hypothesis that fluoxetine, norfluoxetine, and other specific
      serotonin reuptake inhibitor (SSRI) congeners stereoselectively upregulate
      neurosteroid content at doses insufficient to inhibit 5-HT reuptake; although
      they potentiate pentobarbital-induced sedation and exert antiaggressive action.
      Very importantly, the inhibition of 5-HT reuptake lacks stereospecificity and
      requires fluoxetine and norfluoxetine doses that are 50-fold greater than those
      required to increase brain Allo content, potentiate the action of pentobarbital,
      or antagonize isolation-induced aggression. Based on these findings, it could be
      inferred that the increase of brain Allo content elicited by fluoxetine and
      norfluoxetine, rather than the inhibition selective of 5-HT reuptake, may be
      operative in the fluoxetine-induced remission of the behavioral abnormalities
      associated with mood disorders. Therefore, the term "SSRI" may be misleading in
      defining the pharmacological profile of fluoxetine and its congeners. To this
      extent, the term "selective brain steroidogenic stimulants" (SBSSs) could be
      proposed.

PMID- 16432686
TI  - Analgesic and disease modifying effects of interferential current in psoriatic
      arthritis.
AB  - Interferential current (IFC) was suggested to improve the skin manifestations of
      psoriasis vulgaris, possibly by enhancing the intracellular concentration of
      cyclic AMP. We assessed the efficacy of IFC on psoriatic arthritis (PsA). Nine
      consecutive patients were analyzed at baseline and after 16 weeks of IFC therapy.
      Bipolar IFC was applied twice daily to hands, feet plus all affected joints. IFC
      improved SF-36 assessed body pain, but not other SF-36 subscales. Morning
      stiffness, tender joint counts, and physician assessed disease activity improved.
      In contrast, visual analogue scale assessed pain, CRP and ESR measurements were
      unchanged. MRI of the most affected hand or foot documented a tendency towards
      worsened tendinitis, soft tissue swelling, and new joint space narrowing and
      erosions. Bone scintigraphy showed a trend towards deterioration. New joints
      became inflamed within treated sites. Thus IFC has analgesic effects in PsA, but
      does not have a satisfactory disease modifying effect.

PMID- 16432687
TI  - Clinical presentations of chlamydial and non-chlamydial reactive arthritis.
AB  - The aim of this study was to investigate the triggering micro-organisms and the
      clinical as well as laboratory differences between Chlamydial and non-chlamydial
      reactive arthritis (ReA) in a prospective study on 98 patients with
      acute/subacute arthritis. An inciting organism was found in 42 patients. Eighteen
      of these were chlamydial. Fifty-seven percent of all ReA patients were carriers
      for HLA-B27, which increased to 67% in the chlamydial group. Chlamydial ReA
      patients had more urethritis (P<0.05) with a longer period between arthritis and
      inciting infection, significantly lower CRP levels, and involved joint counts
      (P<0.05). Additionally, sacroiliitis was more frequent besides extra-articular
      manifestations in chlamydial ReA group. This study shows that chlamydial ReA
      differs in some points from non-chlamydial ReA, which in turn may affect the
      evaluation of an arthritic patient. ReA due to chlamydia more frequently
      encompasses a monoarticular or oligoarticular clinical picture with predominant
      distal extremity involvement. Non-chlamydial ReA presents higher joint counts and
      may involve upper extremity joints.

PMID- 16432688
TI  - [Rare pathological alterations of the upper cervical spine requiring surgical
      treatment].
AB  - Because of its unique anatomy, specific diseases and lesions arise in the upper
      cervical spine, which differ widely from the rest of the spine. During the last
      two decades standardised diagnostic and therapeutic algorithms have been defined
      for most of the craniocervical pathologies often occurring in combination with an
      underlying disease requiring surgical intervention as well. On the other hand
      there are some very rare phathological alterations: about 20% of the patients
      suffering from neurofibromatosis type I develop spinal deformities. These are
      mostly found in the thoracic and lumbar spine (dystrophic/non-dystrophic type).
      In rare cases the dystrophic neurofibromatosis type I involves the upper cervical
      spine leading to bizarre deformities endangering the spinal cord. An aggressive,
      timely and combined operative therapy is necessary. Patients with Down syndrome
      should be investigated regularly for affections of the upper cervical spine.
      Though only in about 1% of all patients with Down syndrome do instabilities
      require surgical intervention, the upper cervical spine should be screened on a
      regular basis, since neurological changes due to the pathognomy of the underlying
      disease often remain undetected for a long time. The operative therapy of the
      instable os odontoideum in Down syndrome follows the general principles of this
      pathoanatomical variation. Even though the Klippel-Feil syndrome is generally not
      linked with neuropathological findings, rare associated deformities of the upper
      cervical spine should be excluded by proper diagnostic procedures.

PMID- 16432690
TI  - Outcomes of urethral calculi patients in an endemic region and an undiagnosed
      primary fossa navicularis calculus.
AB  - Urethral calculus is a rare form of urolithiasis with an incidence lower than
      0.3%. We determined the outcomes of 15 patients with urethral stone, of which 8
      were pediatric, including an undiagnosed primary fossa navicularis calculus.
      Fifteen consecutive male patients, of whom eight were children, with urethral
      calculi were assessed between 2000 and 2005 with a mean of 19 months' follow-up.
      All stones were fusiform in shape and solitary. Acute urinary retention,
      interrupted or weak stream, pain (penile, urethral, perineal) and gross hematuria
      were the main presenting symptoms in 7 (46.7%), 4 (26.7%), 3 (20%) and 1 (6.6%)
      patient, respectively. Six of them had accompanying urethral pathologies such as
      stenosis (primary or with hypospadias) and diverticulum. Two patients were
      associated with upper urinary tract calculi but none of them secondary to bladder
      calculi. A 50-year-old patient with a primary urethral stone disease had urethral
      meatal stenosis accompanied by lifelong lower urinary tract symptoms. Unlike the
      past reports, urethral stones secondary to bladder calculi were decreasing,
      especially in the pediatric population. However, the pediatric patients in their
      first decade are still under risk secondary to the upper urinary tract calculi or
      the primary ones.

PMID- 16432689
TI  - [Instability of the upper cervical spine due to rheumatism].
AB  - Rheumatic manifestation at the cervical spine occurs in more than 50% of all
      cases in the natural course of this disease. The first cervical manifestation
      takes place in the upper cervical spine. The initial involvement of the C1/C2
      segment leads to atlantodental subluxation. Progressive destruction can result in
      vertical instability, which is characterized by cranial subluxation of the
      odontoid process with the danger of resulting stenosis and cervical myelopathy.
      The goal of diagnosis has to be the early recognition of these changes to
      establish an effective treatment protocol. Persistent pain, neurological
      deficits, and progressive radiological signs for instability are indications for
      operative stabilizing procedures. These procedures avoid progressive destruction
      and improve the prognosis regarding pain decrease, regression of neurological
      deficits, and life expectancy.

PMID- 16432692
TI  - Pediatric urolithiasis: etiology, specific pathogenesis and medical treatment.
AB  - Pediatric urolithiasis is an endemic disease in certain parts of the world,
      namely Turkey and the Far East. As a recurrent pathology which may reveal
      functional as well and morphologic changes in the urinary tract, environmental
      factors together with urogenital abnormalities should be evaluated thoroughly in
      each patient. The aims of management should be complete clearance of stones,
      treatment of urinary tract infections, preservation of renal function and
      prevention of stone recurrence. In addition to certain minimally invasive stone
      removal procedures, treatment of pediatric urolithiasis requires a detailed
      metabolic evaluation in all patients on an individual basis. Obstructive
      pathologies have to be corrected immediately and children with a positive family
      history should be followed carefully with respect to a high likelihood of stone
      re-growth and recurrence. Although specific management of each metabolic
      abnormality seems to be the key factor in the medical management of stone
      disease, as general advice each child should be forced to adequate fluid intake
      which will reveal the urine volume increase in accordance with the body mass
      index. Moreover, medical therapeutic agents which increase urine citrate levels
      should be encouraged.

PMID- 16432691
TI  - Calcium oxalate saturation in dialysis patients with and without primary
      hyperoxaluria.
AB  - Calcium oxalate supersaturation of the blood is associated with deposition of
      crystals in various tissues. We measured the serum levels of oxalate, citrate,
      calcium, and magnesium to estimate their saturation in 112 hemodialysis patients
      without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum
      levels of oxalate and citrate were determined by high-performance capillary
      electrophoresis, while calcium and magnesium were measured by ICP spectroscopy.
      The serum levels of oxalate, citrate, calcium, and magnesium were 44.9+/-16.5,
      138.1+/-54.9 micromol/l, 2.30+/-0.28, and 1.07+/-0.18 mmol/l, respectively, while
      the levels in patients with primary hyperoxaluria were 83.9+/-34.3, 197.9+/-63.5
      micromol/l, 2.53+/-0.15, and 1.14+/-0.34 mmol/l, respectively. Serum calcium
      oxalate saturation (SS), as calculated by the Equil program, was significantly
      correlated with the serum oxalate level. Most patients showed metastable
      supersaturation (1<SS<8.9), which was associated with a serum oxalate level of
      more than 30 micromol/l. Serum saturation exceeded the formation product (SS=8.9)
      in some specimens from patients with type 1 primary hyperoxaluria. The serum
      calcium oxalate saturation [SS(CaOx)] showed a significant positive correlation
      with the levels of oxalate [Ox], calcium [Ca], and citrate [Cit]: [SS(CaOx)]=
      0.3562+34.634[Ox]+0.394[Ca]-0.483[Mg]+0.101[Cit], (all mmol/l, r=0.9848, P<0.01).
      This formula is useful for estimating the saturation. In conclusion, the serum
      oxalate level is a good indicator of calcium oxalate saturation and should be
      monitored accurately while keeping it lower in dialysis patients.

PMID- 16432693
TI  - Circadian distribution of motor-activity in unilaterally 6-hydroxy-dopamine
      lesioned rats.
AB  - Sleep abnormalities in idiopathic Parkinson's disease (PD) frequently consist in
      a reduction of total sleep time and efficacy and subsequent excessive daytime
      sleepiness. As it remains unclear whether these phenomena are part of the disease
      itself or result from pharmacological treatment, animal models for investigating
      the pathophysiology of sleep alterations in PD may add knowledge to this research
      area. In the present study, we investigate whether changes in circadian motor
      activity occur in 6-OHDA-lesioning model for PD, and allow a screening for
      disturbed sleep-waking behaviour. Activity measurements of six male Wistar rats
      with 6-OHDA-lesions in the medial forebrain bundle and six controls were carried
      out in two consecutive 12:12 h light-dark (LD) cycles. A computer-based video
      analysis system, recording the animals' movement tracks was used. Distance
      travelled and number of transitions between movement periods and resting periods
      were determined. Although 6-OHDA-lesioned animals show a reduced locomotor
      activity compared to non-lesioned rats, the circadian distribution basically
      remained intact. However, some lesioning effects were more pronounced in the
      resting phase than in the activity phase, possibly paralleling nocturnal akinesia
      in PD. In order to further elucidate the described phenomena, it will be
      necessary to perform studies combining sleep recordings with locomotor activity
      measurements.

PMID- 16432694
TI  - Modulation of visual inputs to accessory optic system by theophylline during
      hypoxia.
AB  - Neural tissues from fresh water turtles have been electrophysiologically studied
      in vitro due to their significant resistance to hypoxia. Such neurons have
      resting membrane potentials that are similar to intact animals and receive
      similar synaptic inputs evoked by sensory stimuli. One mechanism to reduce the
      brain's metabolic requirement in the absence of oxygenated blood flow was
      investigated by blocking adenosine receptors before and during hypoxia.
      Extracellular and whole-cell patch recordings were made from the basal optic
      nucleus, whose neurons respond to visual stimuli in vitro. While the addition of
      the adenosine antagonist theophylline to oxygenated superfusate had minimal
      effect on the neural activity, theophylline in superfusate bubbled with nitrogen
      strongly increased activity compared to either oxygenated theophylline or control
      superfusate bubbled with nitrogen. The increase in spontaneous activity was due
      to increases to both amplitude and frequency of excitatory synaptic events. Even
      during these increases, the neurons continued to exhibit their direction
      sensitive responses. These results indicate that adenosine may play a role in
      protecting the viability of the brainstem during hypoxia without reducing
      visually mediated brainstem reflex control.

PMID- 16432696
TI  - Beta1-subunit modulates the Nav1.4 sodium channel by changing the surface charge.
AB  - Voltage-gated sodium channels, comprised of a pore-forming alpha-subunit and
      additional regulatory (beta) subunits, play a critical role in regulation of
      neuronal excitability. Mechanisms of regulation of beta-subunits remain elusive.
      We have tested the functional effects of beta1 sodium channel subunit on surface
      charges as a mechanism for channel modulation. HEK-293 cell lines permanently
      transfected with the sole rat skeletal muscle sodium channel alpha-subunit
      (Nav1.4), or co-expressing the sodium channel alpha-subunit and beta1-subunit
      were studied with the whole-cell mode of the patch-clamp technique. At
      physiological extracellular Ca2+ concentration (2 mM), expression of beta1
      subunit did not produce any significant effect on the voltage-dependent
      properties of sodium currents. However, a shift of half-activation potentials of
      sodium channel by changing the extracellular Ca2+ was potentiated when beta1 was
      co-expressed with alpha-subunit. In contrast, the expression of beta1-subunit did
      not affect the Ca2+ binding to the open or to the closed sodium channel pore,
      difference of the effect provoked by extracellular Ca2+ could therefore be
      attributed to an increased in negative surface charge determined by the presence
      of beta1-subunit. These data are in agreement with the hypothesis of a modulation
      of the sodium current by the expression of the highly sialylated beta1-subunit,
      which would alter the channel gating by increasing the density of surface
      negative charges in the vicinity of the sodium channel voltage sensing machinery.

PMID- 16432695
TI  - Modeling postural instability with Galvanic vestibular stimulation.
AB  - In this study the effect of a pseudorandom binaural bipolar Galvanic stimulus
      generated by a sum of nonharmonically related sine waves on postural control was
      functionally assessed using computerized dynamic posturography (CDP), and the
      results compared to vestibulopathic patient populations and astronauts exposed to
      microgravity. The standardized CDP test battery comprised six sensory
      organization tests (SOTs) that combined three visual conditions (eyes open, eyes
      closed, and sway-referenced vision) with two proprioceptive conditions (fixed and
      sway-referenced support surfaces). Subjects (12) performed 18 randomized trials
      (three trials of each of the six SOTs) as a baseline, repeated the 18 trials with
      Galvanic vestibular stimulation (GVS), and then performed a post-GVS baseline. A
      10 min rest period was inserted between each test battery. Anterioposterior
      postural sway increased significantly and was in the abnormal range (fifth
      percentile) during GVS for SOTs where visual input was compromised (sway
      referenced surround) or absent. Postural stability returned to baseline when GVS
      was removed. An analysis of sensory input scores (somatosensory, visual, and
      vestibular) demonstrated the specificity of GVS in distorting vestibular input to
      postural control. The SOT scores observed in astronauts on landing day did not
      differ significantly to that generated by GVS in our normal subjects. GVS also
      induced a similar pattern of instability on CDP as profound bilateral vestibular
      loss, although not as severe. The results suggest that unpredictably varying GVS
      quantitatively and qualitatively models postural instability of vestibular
      origin.

PMID- 16432697
TI  - Power and precision grip force control in three-to-five-year-old children:
      velocity control precedes amplitude control in development.
AB  - The aim of this study was to examine the development of underlying motor control
      strategies in young children by characterizing the changes in performance of a
      visually guided force regulation task using two different grip formations; a
      whole-hand power grip (developmentally easier) and a thumb-index finger precision
      grip (developmentally more advanced). Typically developing preschool children
      (n=50, 3.0-5.5 years) used precision and power grips to perform a ramp and hold
      task with their dominant and non-dominant hands. Participants performed five
      trials with each hand and grip holding the force at 30% of their maximum
      volitional contraction for 3 s. The data were examined for both age-related and
      performance-related changes in motor performance. Across ages, children increased
      in strength, decreased in initial overshoot of the target force level, and
      decreased in rate of force release. Results of a cluster analysis suggest non
      linear changes in the development of force control in preschool children, with a
      plateau in (or maturation of) velocity measures (rate of force increase and force
      decrease) earlier than in amplitude-related measures (initial force overshoot and
      force variability).

PMID- 16432698
TI  - Time-dependent effects of discrete spatial cues on the planning of directed
      movements.
AB  - The degree of preparation of a motor response varies with the information
      available regarding the response that will need to be executed and with the time
      provided to process that information. In experiment 1 we investigated the time
      course of processing the information specified by discrete spatial cues regarding
      the upcoming target of directed movements. For this purpose we varied the number
      of cues that indicated the possible locations of the target and the duration of
      the cue period preceding the target. The results showed that the effects of
      processing the information provided by the cues developed progressively and
      stabilized after 0.2 s. In addition, the level of motor preparation reached was a
      function of number of cues. However, the effect of number of cues occurred even
      in the no cue period condition, i.e. when subjects could not have benefited from
      the information provided by the cues to prepare the response. Further analyses
      suggested the hypothesis that, in the no cue period condition, the effect of
      number of cues resulted from the cues acting as distractors (i.e., interference)
      whereas, with longer cue periods, the effect resulted from the motor preparatory
      process (i.e., facilitation). This hypothesis was tested in experiment 2 where
      the number of cues and the number of distractors were varied inversely. Cues and
      distractors were the same type of stimuli and differed only in their relation to
      the time of presentation of the target. Subjects performed in a directed response
      task and in a control detection task. It was predicted that the facilitatory
      effect of the cues and the interference effect of the distractors on the planning
      of the directed response would oppose each other and produce a non-monotonic
      change of RT across conditions. The results conformed to the prediction and,
      therefore, supported the hypothesis of independent effects of facilitation and
      interference. In addition, we found that the pattern of RT across conditions in
      the detection task differed radically with that in the directed response task.
      This result indicates that the time-dependent effects of cues and distractors are
      contingent on the type of motor response required in the task, and, in particular
      on the spatial requirement on the motor response.

PMID- 16432699
TI  - Facilitated extinction of appetitive instrumental conditioning following
      excitotoxic lesions of the core or the medial shell subregion of the nucleus
      accumbens in rats.
AB  - The nucleus accumbens has been implicated in the control of goal-directed
      behaviour, including instrumental conditioning. Here, we evaluated the effect of
      N-methyl-D: -aspartate (NMDA)-induced excitotoxic lesions restricted to either
      the core or the medial shell subregions of the nucleus accumbens (NAC) on
      extinction in rats using a trial discrete fixed ratio-5 (FR-5) appetitive operant
      procedure. Neither core nor shell lesions of the NAC affected the acquisition of
      instrumental responding. Both lesions facilitated the cessation of responding
      when the instrumental act no longer yielded reinforcement. Our results suggest
      that both the NAC core and medial shell contribute to the control of extinction
      learning of appetitively motivated instrumental behaviour.

PMID- 16432700
TI  - A direct comparison of local dynamic stability during unperturbed standing and
      walking.
AB  - Standing and walking are very different tasks. It might be reasonable, therefore,
      to assume that the mechanisms used to maintain the stability of standing and
      walking should be quite different. However, many studies have shown that postural
      stability measures can generally predict risk of falls, even though most falls
      occur during locomotor tasks and not during postural tasks. This suggests that
      there is at least some commonality among the mechanisms governing the control of
      both standing and walking. The present study was conducted to determine whether
      the postural stability either is or is not directly related to locomotor
      stability. Twenty healthy adults, age 18-73 years, walked on a motorized
      treadmill at their preferred walking speed for three trials of 5 min. They also
      stood on a force plate for three trials of 5 min. Both tasks were performed
      without imposing any additional external perturbations. The motion of each
      subject's trunk segment was recorded and described using a multi-dimensional
      state space defined in the same manner for both tasks. Local dynamic stability
      was quantified from the mean divergence over time of locally perturbed
      trajectories in state space, which was parameterized as a double exponential
      process. Divergence parameters were compared to determine the relationship
      between local dynamic stability during standing and walking. Standing and walking
      exhibited local dynamic stability properties that were significantly different
      (P<0.001) and not correlated (P>0.1). Divergence parameters were also compared to
      traditional center of pressure (COP) measures obtained from standing trials. COP
      measures were significantly correlated to local divergence parameters for
      standing, but not to those for walking. This study provides direct evidence that
      the mechanisms governing standing and walking stability are significantly
      different.

PMID- 16432701
TI  - Direct X-ray radiogrammetry versus dual-energy X-ray absorptiometry: assessment
      of bone density in children treated for acute lymphoblastic leukaemia and growth
      hormone deficiency.
AB  - BACKGROUND: In recent years interest in bone densitometry in children has
      increased. OBJECTIVE: To evaluate the clinical application of digital X-ray
      radiogrammetry (DXR) and compare the results with those of dual-energy X-ray
      absorptiometry (DXA). MATERIALS AND METHODS: A total of 41 children with acute
      lymphoblastic leukaemia (ALL) and 26 children with growth hormone deficiency
      (GHD) were included in this longitudinal study. Radiographs of the left hand were
      obtained and used for DXR. DXA of the total body and of the lumbar spine was
      performed. RESULTS: In both study populations significant correlations between
      DXR and DXA were found, and, with the exception of the correlation between DXR
      bone mineral density (DXR-BMD) and bone mineral apparent density in the GHD
      population, all correlations had a P-value of <0.001. During treatment a change
      in DXR-BMD was found in children with GHD. CONCLUSIONS: Our study showed that DXR
      in a paediatric population shows a strong correlation with DXA of the lumbar
      spine and total body and that it is able to detect a change in BMD during
      treatment.

PMID- 16432702
TI  - Percutaneous treatment of a ruptured superior mesenteric artery aneurysm in a
      child.
AB  - Splanchnic artery aneurysms are very rare in children. We report a 10-year-old
      girl with a large atraumatic ruptured superior mesenteric artery aneurysm that
      was considered inoperable. She was ultimately treated with two percutaneous US
      guided thrombin injections, which led to complete occlusion of the aneurysm. The
      aetiology of the aneurysm remained unclear, but a family history was suggestive
      of a congenital connective tissue disease such as Ehlers-Danlos syndrome subtype
      IV.

PMID- 16432703
TI  - Hypochondrogenesis.

PMID- 16432704
TI  - Thyroid disease in the pediatric patient: emphasizing imaging with sonography.
AB  - Thyroid disease does occur in the pediatric patient, and imaging plays an
      important role in its evaluation. A review is presented of normal development of
      the thyroid gland, the technique and indications for thyroid sonography, and key
      imaging features of congenital thyroid disorders (ectopic or absent thyroid,
      infantile goiter, thyroglossal duct remnants), benign thyroid masses (follicular
      adenoma, degenerative nodules, colloid and thyroid cysts), malignant masses
      (follicular, papillary and medullary carcinoma) and diffuse thyroid disease
      (acute bacterial thyroiditis, Hashimoto's thyroiditis, Grave's disease).

PMID- 16432705
TI  - Visceral larval migrans masquerading as metastatic disease in a toddler with
      Wilms tumor.
AB  - A 22-month-old girl with a renal mass had multiple small pulmonary nodules on CT
      at her initial presentation. After biopsy and neoadjuvant chemotherapy, a Wilms
      tumor was resected and the pulmonary nodules were shown to have regressed on CT.
      Follow-up imaging 4 months after initial diagnosis demonstrated multiple new
      liver lesions and new pulmonary nodules with peripheral eosinophilia. Lung biopsy
      revealed granuloma formation with prominent eosinophils. The serum antibody
      titers for Toxocara canis were elevated. This case illustrates that toxocariasis
      should be considered as a rare differential diagnostic possibility for multiple
      liver lesions and multifocal peripheral pulmonary opacities in young children
      with Wilms tumor.

PMID- 16432706
TI  - How to screen for depression and emotional problems in patients with diabetes:
      comparison of screening characteristics of depression questionnaires, measurement
      of diabetes-specific emotional problems and standard clinical assessment.
AB  - AIMS/HYPOTHESIS: We compared the screening performance of different measures of
      depression: the standard clinical assessment (SCA); the Beck Depression Inventory
      (BDI); the Center of Epidemiological Studies-Depression Scale (CES-D); and the
      Problem Areas in Diabetes (PAID) questionnaire, which assesses diabetes-specific
      distress. We also studied the ability of these measures to detect diabetes
      related distress. MATERIALS AND METHODS: A total of 376 diabetic patients (37.2%
      type 1; 23.9% type 2 without insulin treatment, 38.8% type 2 with insulin)
      completed the BDI and CES-D; patients who screened positive participated in a
      diagnostic interview, the Composite International Diagnostic Interview (CIDI).
      Also, all patients completed the PAID questionnaire. Results of the SCA that
      related to depression diagnosis were reviewed to correct for false negative
      screening results. RESULTS: The prevalence of clinical depression was 14.1%, with
      an additional 18.9% of patients receiving a diagnosis of subclinical depression.
      Sensitivity for clinical depression in SCA (56%) was moderate, whereas BDI, CES-D
      and the PAID questionnaire showed satisfactory sensitivity (87, 79 and 81%,
      respectively). For subclinical depression, the sensitivity of the PAID
      questionnaire (79%) was sufficient, whereas that of SCA (25%) was poor. All
      methods showed low sensitivity for the detection of diabetes-specific emotional
      problems (SCA 19%, CIDI 34%, BDI 60%, CES-D 49%). CONCLUSIONS/INTERPRETATION: The
      screening performance of SCA for clinical and subclinical depression was modest.
      Additional screening for depression using the PAID or another depression
      questionnaire seems reasonable. The ability of depression screening measures to
      identify diabetes-related distress is modest, suggesting that the PAID
      questionnaire could be useful when screening diabetic patients for both
      depression and emotional problems.

PMID- 16432708
TI  - All-cause mortality rates in patients with type 1 diabetes mellitus compared with
      a non-diabetic population from the UK general practice research database, 1992
      1999.
AB  - AIMS/HYPOTHESIS: We compiled up to date estimates of the absolute and relative
      risk of all-cause mortality in patients with type 1 diabetes in the UK. MATERIALS
      AND METHODS: We selected patients with type 1 diabetes (n=7,713), and for each of
      these diabetic subjects five age- and sex-matched control subjects without
      diabetes (n=38,518) from the General Practice Research Database (GPRD). Baseline
      was 1 January 1992; subjects were followed until 1999. The GPRD is a large
      primary-care database containing morbidity and mortality data of a large sample
      representative of the UK population. Deaths occurring in the follow-up period
      were identified. RESULTS: The study comprised 208,178 person-years of follow-up.
      The prevalence of type 1 diabetes was 2.15/1,000 subjects in 1992 (mean age 33
      years, SD 15). Annual mortality rates were 8.0 per 1,000 person-years (95% CI 7.2
      8.9) in type 1 diabetic subjects compared with 2.4 per 1,000 person-years (95% CI
      2.2-2.6) in those without diabetes (hazard ratio [HR]=3.7, 95% CI 3.2-4.3). The
      increased mortality rates in patients with type 1 diabetes were apparent across
      all age-bands. The HR was higher in women (HR=4.5, 95% CI 3.5-5.6 compared with
      non-diabetic women) than men (HR=3.3, 95% CI 2.7-4.0), such that the sex
      difference (p<0.0001) in mortality in the non-diabetic population was abolished
      (p=0.3) in the type 1 diabetic patients. The predominant cause of death in
      patients with type 1 diabetes was cardiovascular disease.
      CONCLUSIONS/INTERPRETATION: Despite advances in care, UK mortality rates in the
      past decade continue to be much greater in patients with type 1 diabetes than in
      those without diabetes.

PMID- 16432707
TI  - In treatment-naive and antiretroviral-treated subjects with HIV, reduced plasma
      adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL
      and LDL apolipoprotein B-100.
AB  - AIMS/HYPOTHESIS: We hypothesised that loss of peripheral fat in HIV patients
      would result in decreased plasma adipocytokines, in particular adiponectin, and
      that this decrease would be associated with changes in VLDL, IDL and LDL
      apolipoprotein B kinetics. METHODS: Plasma adiponectin, leptin and other
      cytokines were measured in uninfected control subjects (n=12) and three HIV
      positive groups comprising treatment-naive patients (n=15) and patients on triple
      antiretroviral therapy containing protease inhibitors (PI, n=15) or non
      nucleoside reverse transcriptase inhibitors (NNRTI, n=25). VLDL, IDL and LDL
      apolipoprotein B kinetics were measured with an infusion of [1-(13)C] leucine.
      Regional body fat was measured with a dual energy X-ray absorptiometry scan.
      Insulin resistance was calculated using homeostasis model assessment (HOMA).
      RESULTS: Adiponectin (median [interquartile range]) was reduced in the treatment
      naive (5.4 microg/ml [4.7-8.5]), PI (5.0 microg/ml [3.3-6.4]) and NNRTI (5.0
      microg/ml [3.1-6.7]) groups compared with controls (9.7 microg/ml [6.9-13.3])
      (p<0.05). In all subjects adiponectin correlated positively with HDL-cholesterol
      levels, the VLDL, IDL and LDL apolipoprotein B fractional clearance rates, and
      with the limb fat:lean body mass ratio (all p<0.01). Adiponectin correlated
      negatively with plasma triglyceride levels and HOMA (p<0.001). In a linear
      regression model that included HOMA, adiponectin was an independent predictor of
      VLDL and HDL-cholesterol levels and the IDL fractional clearance rate. TNF was
      higher in treatment-naive and PI subjects, and soluble TNF receptor superfamily,
      members 1A and 1B (previously known as TNF receptors 1 and 2) was higher in PI
      patients than in control subjects (p<0.05). CONCLUSIONS/INTERPRETATION:
      Adiponectin levels are significantly reduced in treated and untreated HIV
      patients and are predictive of VLDL and IDL apolipoprotein B fractional clearance
      rates. Adiponectin may have a direct effect on lipoprotein metabolism, which may
      be independent of insulin.

PMID- 16432710
TI  - Identification of a dendritic cell population in normal testis and in chronically
      inflamed testis of rats with autoimmune orchitis.
AB  - Experimental autoimmune orchitis (EAO) in the rat is the primary chronic animal
      model for the investigation of one of the main causes of male infertility, viz.,
      testicular inflammation. Dendritic cells (DC) are potent antigen-presenting cells
      that play a fundamental role in autoimmune disease. We investigated the number of
      DC in normal testis and examined whether DC infiltrated the testis during the
      development of EAO. EAO was induced by active immunization with testis homogenate
      and adjuvants in two strains of rat (Wistar and Sprague Dawley). The presence of
      DC in testis was determined, 50 and 80 days after the first immunization, by
      immunohistochemical staining with specific antibodies (OX-62 and CD11c), and then
      the total number of DC was measured by stereological analysis. Labeled cells were
      found only in the interstitial compartment and within granulomas of EAO animals.
      The number of DC in EAO testes increased compared with control rats in both
      strains, whereas the number of OX-62+ and CD11c+ cells in adjuvant controls
      remained unchanged compared with untreated rats. Interspecies variations in the
      quantity of DC were found, with the total number of DC per testis in untreated
      and adjuvant control Sprague-Dawley rats being about three times higher than that
      seen in Wistar rats. Moreover, the increase in DC numbers at 80 days was less
      prominent in EAO testes of Sprague-Dawley rats than in the Wistar strain in which
      EAO was more severe and showed a higher number of granulomae. Thus, we have
      identified the DC population in normal and chronically inflamed testis. The
      increase in DC observed in EAO suggests that, under inflammatory conditions, the
      modified action(s) of these cells is a factor in the induction of the autoimmune
      response in testis.

PMID- 16432709
TI  - Simulated weightlessness changes the cytoskeleton and extracellular matrix
      proteins in papillary thyroid carcinoma cells.
AB  - Studies of astronauts, experimental animals, and cells have shown that, after
      spaceflights, the function of the thyroid is altered by low-gravity conditions.
      The objective of this study was to investigate the cytoskeleton and extracellular
      matrix (ECM) protein synthesis of papillary thyroid cancer cells grown under zero
      g. We investigated alterations of ONCO-DG 1 cells exposed to simulated
      microgravity on a three-dimensional random-positioning machine (clinostat) for 30
      min, 24 h, 48 h, 72 h, and 120 h (n=6, each group). ONCO-DG 1 cells grown under
      microgravity exhibited early alterations of the cytoskeleton and formed
      multicellular spheroids. The cytoskeleton was disintegrated, and nuclei showed
      morphological signs of apoptosis after 30 min. At this time, vimentin was
      increased. Vimentin and cytokeratin were highly disorganized, and microtubules
      (alpha-tubulin) did not display their typical radial array. After 48 h, the
      cytoskeletal changes were nearly reversed. The formation of multicellular
      spheroids continued. In parallel, the accumulation of ECM components, such as
      collagen types I and III, fibronectin, chondroitin sulfate, osteopontin, and
      CD44, increased. The levels of both transforming growth factor beta-1 (TGF
      beta(1)) and TGF-beta receptor type II proteins were elevated from 24 h until 120
      h clinorotation. Gene expression of TGF-beta(1) was clearly enhanced during
      culture under zero g. The amount of E-cadherin was enhanced time-dependently. We
      suggest that simulated weightlessness rapidly affects the cytoskeleton of
      papillary thyroid carcinoma cells and increases the amount of ECM proteins in a
      time-dependent manner.

PMID- 16432712
TI  - Expression patterns of BMPRs in the developing mouse molar.
AB  - During development, Bone Morphogenetic Proteins (BMPs) can induce apoptosis, cell
      growth or differentiation. These different effects are mediated by dimers of two
      types of BMP-receptors (BMPRs). To identify the responding cells during tooth
      development and search for possible tissue-or stage-specificities in the
      receptors involved, the distribution patterns of BMPR-IA, -IB and -II were
      investigated in the mouse molar, from bud to bell stage. At the bud stage, BMP-2
      was suggested to be involved in the formation of an epithelial signaling center,
      the primary enamel knot (PEK), while BMP-4 would mediate the condensation of the
      mesenchyme. Immunostaining showed the presence of BMPR-IA and -II in the
      epithelium instead of BMPR-IB and -II in the mesenchyme. At the cap stage, BMPR
      IB was detected in the epithelium but not BMPR-II, suggesting the existence of
      another type II receptor to form a functional dimer. At the late cap stage in the
      epithelium, BMP-4, BMPR-IA and -II were restricted to the internal part of the
      PEK and the stalk: two apoptotic areas. The three proteins were detected in the
      mesenchyme, showing a strong staining where cusps were about to form. At the late
      bell stage, BMP-2 or -4 may induce cell differentiation. BMPR-IB and -II were
      detected in odontoblasts instead of BMPR-IA and -II in ameloblasts. These results
      provide the first evidence of multiple type I and type II BMP-receptors,
      expressed in the dental epithelium and mesenchyme at different stages of
      development, to signal different cellular activities in a time- and tissue
      specific way.

PMID- 16432711
TI  - T(3) implantation mimics photoperiodically reduced encasement of nerve terminals
      by glial processes in the median eminence of Japanese quail.
AB  - Photoperiodically generated triiodothyronin (T(3)) in the mediobasal hypothalamus
      (MBH) has critical roles in the photoperiodic response of the gonads in Japanese
      quail. In a previous study, we demonstrated seasonal morphological changes in the
      neuro-glial interaction between gonadotrophin-releasing hormone (GnRH) nerve
      terminals and glial endfeet in the median eminence (ME). However, a direct
      relationship between photoperiodically generated T(3) and seasonal neuro-glial
      plasticity in the ME remained unclear. In the present study, we examined the
      effect of T(3) implantation into the MBH on the neuro-glial interaction in the
      ME. T(3) implantation caused testicular growth and reduced encasement of nerve
      terminals in the external zone of the ME. In contrast, no morphological changes
      were observed in birds given an excessive dose of T(3), which did not cause
      testicular growth. These results support the hypothesis that thyroid hormone
      regulates photoperiodic GnRH secretion via neuro-glial plasticity in the ME.

PMID- 16432713
TI  - Nocodazole does not synchronize cells: implications for cell-cycle control and
      whole-culture synchronization.
AB  - It has been predicted that nocodazole-inhibited cells are not synchronized
      because nocodazole-arrested cells with a G2-phase amount of DNA would not have a
      narrow cell-size range reflecting the cell size of some specific, presumably G2
      phase, cell-cycle age. Size measurements of nocodazole-inhibited cells now fully
      confirm this prediction. Further, release from nocodazole inhibition does not
      produce cells that move through the cell cycle mimicking the passage of normal
      unperturbed cells through the cell cycle. Nocodazole, an archetypal whole-culture
      synchronization method, can inhibit growth to produce cells with a G2-phase
      amount of DNA, but such cells are not synchronized. Cells produced by a selective
      (i.e., non-whole-culture) method not only have a specific DNA content, but also
      have a narrow size distribution. The current view of cell-cycle control that is
      based on methods that are not suitable for cell-cycle analysis must therefore be
      reconsidered when results are based on whole-culture synchronization.

PMID- 16432714
TI  - Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK
      signaling and occludin expression in human umbilical vein endothelial cells.
AB  - Female astronauts have been reported to have a higher incidence of post-flight
      orthostatic intolerance (POI) compared with that of their male counterparts. POI
      may result from increased permeability of the endothelial cell (EC) layer in the
      vasculature. The goal of this study has been to determine whether estradiol
      (E(2)) and dihydrotesterone (DHT) alter human umbilical vein ECs (HUVECs)
      responses to short term (10 min) hypergravity (1-3 g) mimicking the g force
      experienced by astronauts during liftoff. E(2) and DHT rapidly (within 5 min)
      activated MAPK (mitogen-activated protein kinase) in HUVEC at 1 g in a receptor
      dependent manner. Liftoff inhibited MAPK phosphorylation, and rapid E(2) and DHT
      activation of MAPK was blocked. Liftoff simulation or brief (5-90 min) treatment
      with E(2) or DHT at 1 g had no effect on the expression of the EC tight-junction
      protein occludin. However, 24-h pre-treatment of HUVECs with E(2) and DHT prior
      to liftoff simulation significantly increased occludin expression, and
      hypergravity exposure did not alter this increase. These data provide evidence
      for a possible protective effect of E(2) and DHT on EC function as indicated by
      increased occludin; this may help maintain the integrity of EC tight junction and
      could thus retard or reduce the incidence of POI.

PMID- 16432715
TI  - Effect of clinical trial publicity on HRT prescribing in Ireland.
AB  - OBJECTIVE: To evaluate the effect of publicity surrounding the Women's Health
      Initiative (WHI) and Million Women (MW) studies on prescribing of all hormone
      replacement therapy (HRT) preparations and bisphosphonates in Ireland. METHODS:
      The General Medical Services (GMS) prescription database was used to identify the
      study population. Prescriptions were identified for HRT and bisphosphonate
      preparations [using WHO Anatomical Therapeutic Chemical (ATC) classification
      codes] in female patients aged 45-69 years in Ireland during a 4-year study
      period (January 2001-December 2004). Prescription rates were calculated monthly.
      Prevalence and incidence of HRT use was examined. RESULTS: There was a
      significant reduction in prevalence for all HRT preparations following the WHI
      trial (test for change in trend p<0.0001), which persisted after the MW study.
      The incidence of combined oestrogen/progestogen HRT declined after the WHI trial
      (test for change in trend p=0.004). Bisphosphonate prescribing showed a
      significant increase throughout the study period (p<0.0001). CONCLUSION: The
      findings suggest that coverage surrounding the publication of clinical trials
      appears to have had a negative impact on the rate of HRT prescribing. The
      findings regarding the coincident increase in use of bisphosphonates may suggest
      that prescribers and users were less likely to regard HRT as an appropriate
      therapy in the management of osteoporosis for some time before guidance was
      issued by the regulatory authorities.

PMID- 16432716
TI  - Limited effect of patient and disease characteristics on compliance with hospital
      antimicrobial guidelines.
AB  - OBJECTIVE: Physicians frequently deviate from guidelines that promote prudent use
      of antimicrobials. We explored to what extent patient and disease characteristics
      were associated with compliance with guideline recommendations for three common
      infections. METHODS: In a 1-year prospective observational study, 1,125
      antimicrobial prescriptions were analysed for compliance with university hospital
      guidelines. RESULTS: Compliance varied significantly between and within the
      groups of infections studied. Compliance was much higher for lower respiratory
      tract infections (LRTIs; 79%) than for sepsis (53%) and urinary tract infections
      (UTIs; 40%). Only predisposing illnesses and active malignancies were associated
      with more compliant prescribing, whereas alcohol/ intravenous drug abuse and
      serum creatinine levels >130 micromol/l were associated with less compliant
      prescribing. Availability of culture results had no impact on compliance with
      guidelines for sepsis but was associated with more compliance in UTIs and less in
      LRTIs. Narrowing initial broad-spectrum antimicrobial therapy to cultured
      pathogens was seldom practised. Most noncompliant prescribing concerned a too
      broad spectrum of activity when compared with guideline-recommended therapy.
      CONCLUSION: Patient characteristics had only a limited impact on compliant
      prescribing for a variety of reasons. Physicians seemed to practise defensive
      prescribing behaviour, favouring treatment success in current patients over loss
      of effectiveness due to resistance in future patients.

PMID- 16432718
TI  - MRI growth patterns of plexiform neurofibromas in patients with neurofibromatosis
      type 1.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an
      incidence of 1:3000. Approximately 30% of NF1 patients develop plexiform
      neurofibromas (PNF) which often cause severe clinical deficits. We studied the
      growth patterns of 256 plexiform neurofibromas (PNF) by magnetic resonance
      imaging (MRI) and associated disfigurement and functional deficits to determine
      whether there are definable growth types of these tumors. Retrospectively, we
      evaluated MRI scans obtained during 1997 to 2003 of 256 plexiform neurofibromas
      from 202 patients with NF1. Clinical investigation was carried out at the same
      time as the MRI scans. We identified three growth patterns: superficial in 59,
      displacing in 76, and invasive growth in 121 tumors. The majority (52%) of
      invasive PNF were found in the face, head and neck area. While superficial PNF
      primarily caused aesthetic problems, displacing PNF led in most cases to
      aesthetic problems and pain, while invasive PNF led mainly to functional deficits
      and disfigurement. Our study demonstrates that PNF have different growth patterns
      that are associated with specific clinical features. Classification of PNF may
      open new opportunities in clinical management, especially regarding decisions and
      options associated with surgical intervention.

PMID- 16432721
TI  - Development of an SdFFF-ETAAS hyphenated technique for dimensional and elemental
      characterization of colloids.
AB  - Direct hyphenation of electrothermal atomic-absorption spectroscopy (ETAAS) to
      sedimentation field-flow fractionation (SdFFF) has been developed to enable
      elemental characterization of submicron particles as a function of size. This
      hyphenation is particularly suitable for characterizing colloidal particles of
      environmental interest, for example water-borne particles. The interface is an
      automatic capillary injection device (CID) which enables direct introduction of
      large and variable volumes of colloidal particle suspensions into a hot graphite
      furnace, thus preconcentrating the colloidal particles on the furnace walls. The
      method was validated by determination of Fe in certified submicron Fe2O3. The
      procedure was set up by first optimizing the SdFFF fractionation under programmed
      field conditions, thus enabling optimum fractionation of particle size. The ETAAS
      procedure was then tested to determine whether it could be used for direct
      analysis of Fe2O3 slurries without the need for a mineralization step. CID
      coupled to ETAAS was subsequently exploited for its ability to enhance the
      sensitivity, because of the increased injection volume. Statistical tests and
      data handling were conducted to prove the suitability of the ETAAS-CID module.
      Finally, off-line and on-line ETAAS-CID-SdFFF hyphenation were investigated.
      These experiments emphasized the advantages of the on-line coupling, because it
      enables synchronized sampling, enrichment, and elemental analysis of the flowing
      eluate. The benefits of the proposed hyphenation are the high specificity of
      analytical detection, increased sensitivity, reduction of analysis time, and
      minimum sample handling and contamination.

PMID- 16432719
TI  - Impact of sentinel lymph node biopsy in patients with Merkel cell carcinoma:
      results of a prospective study and review of the literature.
AB  - PURPOSE: Merkel cell carcinoma (MCC) is the most aggressive of the cutaneous
      malignancies, showing a propensity to spread to regional lymph nodes (LNs). The
      aim of this prospective study was to examine the feasibility and clinical impact
      of sentinel lymph node biopsy (SLNB) in this cutaneous malignancy. METHODS: The
      study population comprised 23 patients with stage I MCC (median age 70 years,
      range 50-85 years). Lymphoscintigraphic mapping with( 99 m)Tc-nanocolloid was
      performed in all patients. Sentinel lymph nodes (SLNs) were identified, excised
      and analysed in serial sections by conventional histopathology and cytokeratin-20
      immunohistochemistry. RESULTS: Metastatic disease was determined in the SLNs of
      11 patients (47.8%). Elective lymph node dissection (ELND) was performed in eight
      of these 11 patients, four of whom had additional positive LNs. During follow-up
      (median 36.1 months, range 3-79 months), seven of the 23 patients (30%) relapsed:
      four had a local recurrence and three, in-transit metastases. Recurrence
      developed in two SLN-negative patients with local LN metastases and in one SLN
      positive patient with distant metastases. This patient died, representing the
      only tumour-related death in our sample. Median survival was 49.1 and 35.5 months
      for SLN-negative and SLN-positive patients, respectively. This difference was not
      statistically significant (p=0.3452). CONCLUSION: SLNB allows for exact nodal
      staging in patients with MCC. Whether additional ELND is of further benefit
      remains unclear.

PMID- 16432722
TI  - Confirmatory determination of organochlorine pesticides in surface waters using
      LC/APCI/tandem mass spectrometry open diamond.
AB  - A confirmatory method for the determination of organochlorine pesticides (OCPs)
      and their metabolites (endrin, alpha-endosulfan, beta-endosulfan, endosulfan
      sulfate, heptachlor, heptachlor epoxide, 2,4'-DDD, 4,4'-DDD, 2,4'-DDE 4,4'-DDE,
      2,4'-DDT, and 4,4'-DDT) in surface waters using liquid chromatography
      /APCI/tandem mass spectrometry has been developed. Chromatographic separation was
      carried out on a ChromSpher 5 Pesticide column using a gradient elution with
      mobile phase 1mM ammonium acetate-acetonitrile. Endrin, alpha-endosulfan, beta
      endosulfan , endosulfan sulfate, heptachlor and heptachlor epoxide were
      determined in the negative ionization mode, while the rest compounds in positive
      ionization mode. For the identification of the analytes, two multireaction
      monitoring transitions were selected per compounds except for the heptachlor
      which selected ion monitoring was used. The linearity of the optimized method
      ranges after SPE concentration, from 0.009 to 30.60 microgL(-1) with correlation
      coefficients greater than 0.99. The method recovery values varied from 72 to 119
      % for the different fortification levels . The developed method was successfully
      applied to determine OCPs and their metabolites in surface water samples
      collected near paddy fields in growing season of rice, at year 2005 in
      Pathumthani province, Thailand. Endosulfan sulfate was detected in five out of
      seven samples and three of them could be quantitated in the range of 0.31 to 0.50
      microgL(-1).

PMID- 16432720
TI  - pWormgatePro enables promoter-driven knockdown by hairpin RNA interference of
      muscle and neuronal gene products in Caenorhabditis elegans.
AB  - Recent advances in genome research and RNA interference (RNAi) technology have
      accelerated the adoption of genome-wide experimental approaches for determining
      gene function in the model organism Caenorhabditis elegans. Despite recent
      successes, the application of RNAi is limited when gene knockdown causes complex
      phenotypes or embryonic lethality. Recently, the high-throughput pWormgate
      cloning system has been introduced as a tool to efficiently generate heat-shock
      inducible hairpin RNA constructs using the Gateway recombination technology. We
      have modified pWormgate into a versatile hairpin cloning plasmid, pWormgatePro,
      which facilitates temporally and spatially inducible hairpin RNAi using
      constitutively active, tissue-specific promoters. To demonstrate its utility we
      knocked down unc-22 in body wall muscles as well as the axon guidance gene unc-5
      in the nervous system indicating that promoter-driven hairpins can overcome the
      neuronal resistance to RNAi. Using pWormgatePro we also show that RNAi in the
      nervous system of C. elegans is non-autonomous and that spreading of the RNAi
      signal from neurons to muscle is substantially reduced but not abolished in
      spreading-defective sid-1 mutant animals. Our findings illustrate the
      effectiveness of pWormgatePro for gene silencing in muscle cells and neurons and
      bring forward the possibility of applying tissue-specific RNAi on a genome-wide
      scale.

PMID- 16432723
TI  - Reinvestigation of the method used to map the electronic structure of blue copper
      proteins by NMR relaxation.
AB  - A previous method for mapping the electron spin distribution in blue copper
      proteins by paramagnetic nuclear magnetic resonance (NMR) relaxation (Hansen DF,
      Led JJ, 2004, J Am Chem Soc 126:1247-1253) suggested that the blue copper site of
      plastocyanin from Anabaena variabilis (A.v.) is less covalent than those found
      for other plastocyanins by other experimental methods, such as X-ray absorption
      spectroscopy. Here, a detailed spectroscopic study revealed that the electronic
      structure of A.v. plastocyanin is similar to those of other plastocyanins.
      Therefore, the NMR approach was reinvestigated using a more accurate geometric
      structure as the basis for the mapping, in contrast to the previous approach, as
      well as a more complete spin distribution model including Gaussian-type natural
      atomic orbitals instead of Slater-type hydrogen-like atomic orbitals. The
      refinement results in a good agreement between the electron spin density derived
      from paramagnetic NMR and the electronic structure description obtained by the
      other experimental methods. The refined approach was evaluated against density
      functional theory (DFT) calculations on a model complex of the metal site of
      plastocyanin in the crystal phase. In general, the agreement between the
      experimental paramagnetic relaxation rates and the corresponding rates obtained
      by the DFT calculations is good. Small deviations are attributed to minor
      differences between the solution structure and the crystal structure outside the
      first coordination sphere. Overall, the refined approach provides a complementary
      experimental method for determining the electronic structure of paramagnetic
      metalloproteins, provided that an accurate geometric structure is available.

PMID- 16432724
TI  - Targeting polyketide synthase gene pool within actinomycetes: new degenerate
      primers.
AB  - Natural products provide a unique element of molecular diversity and biological
      functionality and they are still indispensable for drug discovery. The
      polyketides, comprising a large and structurally diverse family of bioactive
      natural products, have been isolated from a group of mycelia-forming Gram
      positive microorganisms, the actinomycetes. Relatively high amino acid sequence
      identity of the actinomycetes type I polyketide synthases (PKSs) was used to
      design three degenerate primer pairs for homology-based PCR detection of novel
      PKS genes, with particular interest into PKSs involved in biosynthesis of
      immunosuppressive-like metabolites. The stepdown PCR method, described here,
      enables fast insight into the PKS arsenal within actinomycetes. Designed primers
      and stepdown PCR were applied for the analysis of two natural isolates,
      Streptomyces sp. strains NP13 and MS405. Sequence analysis of chosen clones
      revealed the presence of two distinctive sequences in strain Streptomyces sp.
      NP13, but only one of these showed homology to PKS-related sequences. On
      analysing PCR amplicons derived from Streptomyces sp. strain MS405, three
      different PKS-related sequences were identified demonstrating a potential of
      designed primers to target PKS gene pool within single organism.

PMID- 16432725
TI  - Femur ostochondroma and secondary pseudoaneurysm of the popliteal artery.
AB  - Osteochondroma is the most common skeletal benign tumour. It may present in a
      solitary form or as part of an autosomal dominant hereditary syndrome affecting
      several bones simultaneously. It is found most often in the knee region. It is
      generally asymptomatic although it may cause complications, including vascular
      disorders. In view of anatomical circumstances, the popliteal artery is most
      frequently involved in this type of complication. This is a case report of a 9
      year-old boy who referred with pain in the distal third of his femur.
      Osteochondroma was initially diagnosed through plain X-ray. In view of worsening
      symptoms, an ultrasound and magnetic resonance imaging were performed and the
      patient was diagnosed with pseudoaneurysm of the popliteal artery.

PMID- 16432726
TI  - Behavioral guides for sensory neurophysiology.
AB  - The study of natural behavior is important for understanding the coding schemes
      of sensory systems. The jamming avoidance response of the weakly electric fish
      Eigenmannia is an excellent example of a bottom-up approach, in which behavioral
      analyses guided neurophysiological studies. These studies started from the
      electroreceptive sense organs to the motor output consisting of pacemaker
      neurons. Going in the opposite direction, from the central nervous system to
      lower centers, is the characteristic of the top-down approach. Although this
      approach is perhaps more difficult than the bottom-up approach, it was
      successfully employed in the neuroethological analysis of sound localization in
      the barn owl. In the latter studies, high-order neurons selective for complex
      natural stimuli led to the discovery of neural pathways and networks responsible
      for the genesis of the stimulus selectivity. Comparison of Eigenmannia and barn
      owls, and their neural systems, has revealed similarities in network designs,
      such as parallel pathways and their convergence to produce stimulus selectivity
      necessary for detection of natural stimuli.

PMID- 16432727
TI  - Head-bobbing and non-bobbing walking of black-headed gulls (Larus ridibundus).
AB  - Head-bobbing walking (HBW) and non-bobbing walking (NBW) of black-headed gulls
      were compared from kinematic and behavioral/environmental viewpoints. The birds
      walked with a longer stride length and lower stride frequency during the HBW than
      during the NBW. With respect to these two parameters, the HBW of black-headed
      gulls was similar to that of other head-bobbers, and the NBW was similar to that
      of other non-bobbers. The stride length and the amplitude of head bobbing were
      correlated. These results suggest that the head-bobbing and gait parameters are
      related. From a behavioral viewpoint, HBW was observed during seeking-type
      foraging by wading, and NBW was observed during waiting-type foraging on a flat
      substrate. The type of foraging behavior and/or substrate condition probably
      determines whether the birds walk with or without head bobbing.

PMID- 16432728
TI  - The influence of the atmospheric boundary layer on nocturnal layers of noctuids
      and other moths migrating over southern Britain.
AB  - Insects migrating at high altitude over southern Britain have been continuously
      monitored by automatically operating, vertical-looking radars over a period of
      several years. During some occasions in the summer months, the migrants were
      observed to form well-defined layer concentrations, typically at heights of 200
      400 m, in the stable night-time atmosphere. Under these conditions, insects are
      likely to have control over their vertical movements and are selecting flight
      heights that are favourable for long-range migration. We therefore investigated
      the factors influencing the formation of these insect layers by comparing radar
      measurements of the vertical distribution of insect density with meteorological
      profiles generated by the UK Meteorological Office's (UKMO) Unified Model (UM).
      Radar-derived measurements of mass and displacement speed, along with data from
      Rothamsted Insect Survey light traps, provided information on the identity of the
      migrants. We present here three case studies where noctuid and pyralid moths
      contributed substantially to the observed layers. The major meteorological
      factors influencing the layer concentrations appeared to be: (a) the altitude of
      the warmest air, (b) heights corresponding to temperature preferences or
      thresholds for sustained migration and (c) on nights when air temperatures are
      relatively high, wind-speed maxima associated with the nocturnal jet. Back
      trajectories indicated that layer duration may have been determined by the
      distance to the coast. Overall, the unique combination of meteorological data
      from the UM and insect data from entomological radar described here show
      considerable promise for systematic studies of high-altitude insect layering.

PMID- 16432729
TI  - Do geese fully develop brood patches? A histological analysis of lesser snow
      geese (Chen caerulescens caerulescens) and Ross's geese (C. rossii).
AB  - Most birds develop brood patches before incubation; epidermis and dermis in the
      brood patch region thicken, and the dermal connective tissue becomes increasingly
      vascularized and infiltrated by leukocytes. However, current dogma states that
      waterfowl incubate without modifications of skin within the brood patch region.
      The incubation periods of lesser snow geese (Chen caerulescens caerulescens;
      hereafter called snow geese) and Ross's geese (C. rossii) are 2-6 days shorter
      than those of other goose species; only females incubate. Thus, we hypothesized
      that such short incubation periods would require fully developed brood patches
      for sufficient heat transfer from incubating parents to eggs. We tested this
      hypothesis by analyzing the skin histology of abdominal regions of snow and
      Ross's geese collected at Karrak Lake, Nunavut, Canada. For female snow geese, we
      found that epidermis and dermis had thickened and vascularization of dermis was
      14 times greater, on average, than that observed in males (n=5 pairs). Our
      results for Ross's geese (n=5 pairs) were more variable, wherein only one of five
      female Ross's geese fully developed a brood patch. Our results are consistent
      with three hypotheses about brood patch development and its relationship with
      different energetic cost-benefit relationships, resulting from differences in
      embryonic development and body size.

PMID- 16432730
TI  - Food deprivation alters osmoregulatory and metabolic responses to salinity
      acclimation in gilthead sea bream Sparus auratus.
AB  - The influence of acclimation to different environmental salinities (low salinity
      water, LSW; seawater, SW; and hyper saline water, HSW) and feeding conditions
      (fed and food deprived) for 14 days was assessed on osmoregulation and energy
      metabolism of several tissues of gilthead sea bream Sparus auratus. Fish were
      randomly assigned to one of six treatments: fed fish in LSW, SW, and HSW, and
      food-deprived fish in LSW, SW, and HSW. After 14 days, plasma, liver, gills,
      kidney and brain were taken for the assessment of plasma osmolality, plasma
      cortisol, metabolites and the activity of several enzymes involved in energy
      metabolism. Food deprivation abolished or attenuated the increase in gill Na+,K+
      ATPase activity observed in LSW- and HSW-acclimated fish, respectively. In
      addition, a linear relationship between renal Na+,K+-ATPase activity and
      environmental salinity was observed after food deprivation, but values decreased
      with respect to fed fish. Food-deprived fish acclimated to extreme salinities
      increased production of glucose through hepatic gluconeogenesis, and the glucose
      produced was apparently exported to other tissues and served to sustain plasma
      glucose levels. Salinity acclimation to extreme salinities enhanced activity of
      osmoregulatory organs, which is probably sustained by higher glucose use in fed
      fish but by increased use of other fuels, such as lactate and amino acids in food
      deprived fish.

PMID- 16432731
TI  - [The European Vision Institute. Opening up new frontiers?].
AB  - The European Vision Institute EEIG (EVI) creates a new legal entity based on
      Community law to facilitate and encourage cross-border co-operation in vision
      research. Its major objectives are to conduct and support research, training,
      health information dissemination and other programmes with respect to blinding
      eye diseases, visual disorders, mechanisms of visual function, preservation of
      sight and the special health problems and requirements of the blind and visually
      disabled. EVI aims to foster centres in the EU in capacity building for
      innovative projects, to increase the flexibility, attractiveness and
      competitiveness of research careers, especially for young researchers. In
      addition, EVI will serve to co-ordinate activities with patient organisations and
      to build a pan-European platform for clinical trials.

PMID- 16432732
TI  - [Impaired color perception after a gunshot wound to the head].

PMID- 16432733
TI  - [A symptom oriented diagnostic approach to the workup of secondary forms of
      uveitis -- an internet based program for better and easier orientation in
      differential diagnosis].
AB  - BACKGROUND: The long list of ophthalmologic findings and symptoms at a baseline
      examination of a patient with uveitis can have an impact on further laboratory
      workup and differential diagnosis. METHODS: Based on publications and previous
      work, a decision tree was transformed into the expert system shell D3. A web
      based Java Servlet was then programmed and published on our website
      (http://www.uveitiscenter.de at DiagnoseFinder). Ophthalmologic findings and
      symptoms of the patient can be checked with this online questionnaire, and
      recommendations for further laboratory tests and further care of the patient
      received. RESULTS: Retrospective analysis of 62 patients with characteristic
      features of secondary uveitis showed a good correlation between the actual
      diagnosis of the patient and the diagnosis found by the program. In 74% of cases,
      the correct diagnosis was found among other options. In 37%, only the correct
      diagnosis was found, while in 37% the correct diagnosis was found among other
      probable diagnoses. Not all forms of secondary uveitis were found easily by the
      software. CONCLUSION: This program is meant to be an easily accessible and simply
      employable help for the care of patients with a secondary form of uveitis. It is
      intended to be a support not only for residents in particular, but also for
      ophthalmologists in private practice who rarely treat patients with uveitis.

PMID- 16432734
TI  - QTL analysis of yield traits in an advanced backcross population derived from a
      cultivated Andean x wild common bean (Phaseolus vulgaris L.) cross.
AB  - Advanced backcross QTL analysis was used to identify quantitative trait loci
      (QTL) for agronomic performance in a population of BC2F(3:5) introgression lines
      created from the cross of a Colombian large red-seeded commercial cultivar, ICA
      Cerinza, and a wild common bean accession, G24404. A total of 157 lines were
      evaluated for phenological traits, plant architecture, seed weight, yield and
      yield components in replicated trials in three environments in Colombia and
      genotyped with microsatellite, SCAR, and phaseolin markers that were used to
      create a genetic map that covered all 11 linkage groups of the common bean genome
      with markers spaced at an average distance of every 10.4 cM. Segregation
      distortion was most significant in regions orthologous for a seed coat color
      locus (R-C) on linkage group b08 and two domestication syndrome genes, one on
      linkage group b01 at the determinacy (fin) locus and the other on linkage group
      b02 at the seed-shattering (st) locus. Composite interval mapping analysis
      identified a total of 41 significant QTL for the eight traits measured of which
      five for seed weight, two for days to flowering, and one for yield were
      consistent across two or more environments. QTL were located on every linkage
      group with b06 showing the greatest number of independent loci. A total of 13 QTL
      for plant height, yield and yield components along with a single QTL for seed
      size showed positive alleles from the wild parent while the remaining QTL showed
      positive alleles from the cultivated parent. Some QTL co-localized with regions
      that had previously been described to be important for these traits. Compensation
      was observed between greater pod and seed production and smaller seed size and
      may have resulted from QTL for these traits being linked or pleiotropic. Although
      wild beans have been used before to transfer biotic stress resistance traits,
      this study is the first to attempt to simultaneously obtain a higher yield
      potential from wild beans and to analyze this trait with single-copy markers. The
      wild accession was notable for being from a unique center of diversity and for
      contributing positive alleles for yield and other traits to the introgression
      lines showing the potential that advanced backcrossing has in common bean
      improvement.

PMID- 16432735
TI  - Cloning and comparative analysis of the gene encoding diacylglycerol
      acyltransferase from wild type and cultivated soybean.
AB  - Diacylglycerol acyltransferase (DGAT), as an important enzyme in triacylglycerol
      synthesis, catalyzes the final acylation of the Kennedy pathway. In the present
      study, the GmDGAT gene was cloned from Glycine max by using AtDGAT as a query to
      search against the soybean EST database and the rapid amplification of cDNA ends
      (RACE) method. Allelic genes were also isolated from 13 soybean accessions and
      the divergence of the deduced amino acid sequences were compared. The comparison
      reveals that although GmDGAT is a highly conserved protein, several differences
      of insertion/deletion were identified in the N-terminal region of the GmDGATs
      from various soybean accessions. In the C-terminal regions, a single amino acid
      mutation specific to both G. max and G. soja was also found. The GmDGAT genomic
      sequences were further cloned and the number and size of exons in the DGAT
      genomic sequence were very similar among different plant species, whereas the
      introns were more diverged. These results may have significance in elucidating
      the genetic diversity of the GmDGAT among the soybean subgenus.

PMID- 16432736
TI  - Doubled haploid versus S1 family recurrent selection for testcross performance in
      a maize population.
AB  - Theoretically, in a recurrent selection program, the use of doubled haploids (DH)
      can increase genetic advance per unit of time. To evaluate the efficiency
      expected from the use of DH for the improvement of grain yield in a maize (Zea
      mays L.) population, two recurrent selection programs for testcross performance
      were initiated using testcross progenies from DH lines and S1 families. In 4
      years one selection cycle using DH and two selection cycles using S1 families
      were carried out with the same selection intensity for both methods. As expected,
      testcross genetic variance was twice as high among DH lines as among S1 families.
      The predicted genetic gain was 8.2% for the DH selection cycle, and 10.6% for the
      two S1 selection cycles, giving a per year advantage of 29% for the S1 family
      method over the DH method with a cycle of 4 years. With a 3-year cycle for the DH
      method, both methods were expected to be equivalent. Using a tester related to
      the one used for selection, the genetic gains obtained were equivalent for both
      methods: 6.6% for the DH cycle and 7.0% for the two S1 cycles. With a 3-year
      cycle for the DH method, the advantage would have been in favor of DH method.
      Furthermore, the DH method has the advantage of simultaneously producing lines
      that are directly usable as parents of a hybrid. Thus, if the genetic advance per
      unit of time is evaluated at the level of developed varieties even with the same
      or with a lower genetic advance in population improvement, the DH method appears
      to be the most efficient.

PMID- 16432737
TI  - Mapping quantitative trait loci for yield components and morphological traits in
      an advanced backcross population between Oryza grandiglumis and the O. sativa
      japonica cultivar Hwaseongbyeo.
AB  - Introgression has been achieved from wild species Oryza grandiglumis (2n = 48,
      CCDD, Acc. No. 101154) into O. sativa subsp. japonica cv. Hwaseongbyeo as a
      recurrent parent. An advanced introgression (backcross) line, HG101, produced
      from a single plant from BC5F3 families resembled Hwaseongbyeo, but it showed
      differences from Hwaseongbyeo in several traits, including days to heading and
      culm length. To detect the introgressions, 450 microsatellite markers of known
      chromosomal position were used for the parental survey. Of the 450 markers, 51
      (11.3%) detected O. grandiglumis segments in HG101. To characterize the effects
      of alien genes introgressed into HG101, an F(2:3) population (150 families) from
      the cross Hwaseongbyeo/HG101 was developed and evaluated for 13 agronomic traits.
      Several lines outperformed Hwaseongbyeo in several traits, including days to
      heading. Genotypes were determined for 150 F2 plants using simple sequence repeat
      markers. Qualitative trait locus (QTL) analysis was carried out to determine the
      relationship between marker genotype and the traits evaluated. A total of 39 QTL
      and 1 gene conferring resistance to blast isolate were identified using single
      point analysis. Phenotypic variation associated with each QTL ranged from 4.2 to
      30.5%. For 18 (46.2%) of the QTL identified in this study, the O. grandiglumis
      derived alleles contributed a desirable agronomic effect despite the overall
      undesirable characteristics of the wild phenotype. Favorable wild alleles were
      detected for days to heading, spikelets per panicle, and grain shape traits.
      Grain shape QTL for grain weight, thickness, and width identified in the F(2:3)
      lines were further confirmed based on the F4 progeny test. The confirmed locus,
      tgw2 for grain weight is of particular interest because of its independence from
      undesirable height and maturity. Several QTL controlling amylose content and
      grain traits have not been detected in the previous QTL studies between Oryza
      cultivars, indicating potentially novel alleles from O. grandiglumis. The QTL
      detected in this study could be a rich source of natural genetic variation
      underlying the evolution and breeding of rice.

PMID- 16432739
TI  - Estimation of genetic parameters of a DH wheat population grown at different N
      stress levels characterized by probe genotypes.
AB  - Low market prices and environmental concerns in Europe favor lower input wheat
      production systems. To efficiently breed for new varieties adapted to low input
      management while maintaining high yield levels, our objective was to characterize
      the heritability and its components for yield and nitrogen traits under different
      nitrogen levels. Two hundred and twenty-two doubled-haploid (DH) lines from the
      cross between Arche (tolerant) and Recital (sensitive) were tested in France at
      four locations in 2000, and three in 2001, under high (N+) and low (N-) nitrogen
      supplies. The response of yield to the environment of four probe genotypes, the
      parents and two controls, were tested and used as descriptors of these
      environments. Grain yield (GY), its components, and grain and straw nitrogen,
      called nitrogen traits, were studied. A factorial regression was performed to
      assess the sensitivity (slope) of the DH lines to nitrogen stress and their
      performance to low nitrogen supply. An index based on the nitrogen nutrition
      index at flowering of the probe genotype Recital was the best descriptor of the
      environment stress. Heritabilities of yield and nitrogen traits for both nitrogen
      supplies were always above 0.6. When nitrogen stress increased, heritabilities
      decreased and genotype x nitrogen interaction variances increased. The decrease
      in heritability was mainly explained by a decrease in genetic variance. Genetic
      variation for sensitivity to nitrogen stress and performance under low nitrogen
      supply were shown in the population. GY decreased from 278 to 760 g/m2 per unit
      of nitrogen stress index increase and GY under moderate nitrogen stress varied
      from 340 to 613 g/m2. Those contrasted reactions revealed specific lines to
      include in breeding programs for improving GY under low nitrogen supply.

PMID- 16432738
TI  - A microcolinearity study at the earliness per se gene Eps-A(m)1 region reveals an
      ancient duplication that preceded the wheat-rice divergence.
AB  - Wheat flowering is controlled by numerous genes, which respond to environmental
      signals such as photoperiod and vernalization. Earliness per se (Eps) genes
      control flowering time independently of these environmental cues and are
      responsible for the fine tuning of flowering time. We recently mapped the Eps
      A(m)1 gene on the end of Triticum monococcum chromosome arm 1A(m)L. As a part of
      our efforts to clone Eps-A(m)1 we developed PCR markers flanking this gene within
      a 2.7 cM interval. We screened more than one thousand gametes with these markers
      and identified 27 lines with recombination between them. Recombinant lines were
      used to generate a high-density map and to investigate the microcolinearity
      between wheat and rice in this region. We mapped ten genes from a 149 kb region
      located at the distal part of rice chromosome 5 (cdo393 - Ndk3) on a 3.7 cM
      region on wheat chromosome one. This region is part of an ancient duplication
      between rice chromosomes 5 and 1. Genes present in both rice chromosomes were
      less similar to each other than to the closest wheat orthologues, suggesting that
      this duplication preceded the divergence between wheat and rice. This hypothesis
      was supported by the presence of 18 loci duplicated both in rice chromosomes 5
      and 1 and in the colinear wheat chromosomes from homologous groups 1 and 3.
      Independent gene deletions in wheat and rice lineages explain the alternations of
      colinearity between rice chromosome 5 and wheat chromosomes 1 and 3. Colinearity
      between the end of rice chromosome 5 and wheat chromosome 1 was also interrupted
      by a small inversion, and several non-colinear genes. These results suggest that
      the distal region of the long arm of wheat chromosome 1 was involved in numerous
      changes that differentiated wheat and rice genomes. This comparative study
      provided sufficient markers to saturate the Eps-A(m)1 gene region and to
      precisely map this gene within a 0.9 cM interval flanked by the VatpC and Smp
      loci.

PMID- 16432740
TI  - [Efficacy of opioid analgesia at the superior cervical ganglion in neuropathic
      head and facial pain].
AB  - The efficacy of ganglionic local opioid analgesia (GLOA) at the superior cervical
      ganglion (SCG) was retrospectively investigated in 74 consecutive patients with
      neuropathic pain in the head and face region. It was possible to retrospectively
      analyze the short-term and medium-term treatment results in 64 of 74 patients.
      The long-term effect was subsequently determined using a standardized
      questionnaire. The short-term analgesic effect of the first blockade by GLOA was
      significant with a mean pain reduction of 52% (p < 0.001). Within a span of 20
      min the mean pain intensity decreased from 65 to 28 on a visual analogue scale. A
      clinically relevant pain reduction (> or = 30%) was observed in 73% of the
      patients. The proportion of responders (pain reduction > or = 50%) was 59% after
      the first blockade. Patients with zoster or trigeminal neuralgia experienced
      greater pain relief than patients with atypical facial pain or longer lasting
      postzoster neuralgia. During the course of the blockade series with an average
      duration of 33 days, a significant medium-term pain reduction of 30% was noted.
      In the first 3 treatment days, the level of continuous pain declined from 6.3 to
      4.3 on a numerical rating scale. Short-term responders reported a better medium
      term pain reduction than nonresponders. After 3 years (range: 5 months to 6
      years), 21% of 52 patients remained free of pain. The other patients reported
      often only minimal residual pain or a decrease of pain severity and duration.
      According to these results, GLOA at the SCG can represent a suitable and simple
      treatment option for neuropathic facial pain.

PMID- 16432741
TI  - [Ignition and burning of biological tissue under simulated CO2-laser surgery
      conditions].
AB  - BACKGROUND: Laser surgery in endoscopy has greatly enhanced the surgical
      armamentarium for treating various laryngeal and hypopharyngeal disorders, but
      harbours a risk of tissue ignition and inflammation of surgical and anaesthetic
      instrumentation. However, even if non-inflammable material is used, there is
      still a residual fire hazard from endogenous tissue that may develop an ignitable
      aerosol (so-called laser smog) as an effect of laser irradiation. The aim of this
      study was to investigate how tissue carbonisation and vaporisation contributes to
      the risk of airway fire. METHODS: For the simulation of gas accumulation in the
      hypopharynx and larynx following the European standard ISO-11990, a cylindrical
      steel chamber with an open and a closed end has been used to simulate the
      operative setting. Pork meat chunks with a tissue composition similar to the
      larynx and hypopharynx such as fat, muscle, cartilage and bone were introduced
      into this chamber. Ventilation was achieved through jet ventilation with
      disposable, non-inflammable laser jet catheters. The tissue was then repeatedly
      exposed to a laser beam in super-pulse mode (pulse rate 250 Hz) with various
      intensities and exposure lengths at an impact angle of 75 degrees. The laser
      intensity was varied from 2 to 15 W. The type, duration, intensity and incidence
      of tissue ignition were recorded and analysed. RESULTS: The degree of tissue
      ignition correlated with laser intensity. Low laser intensity caused spark
      formation whereas high intensity resulted in sustained tissue fire. The type of
      tissue had an impact on ignition intensity thereby showing lower ignition
      thresholds and higher ignition susceptibility in fat-containing tissue compared
      to muscle. The most important factor for occurrence of tissue ignition was the
      chamber oxygen concentration which displayed an inverse correlation with the time
      until tissue ignition. Oxygen concentrations of 35% led to tissue ignition in 42
      s, 40% oxygen in 20 s. Oxygen concentrations higher than 60% resulted in
      immediate tissue ignition. CONCLUSIONS: Despite the use of non-inflammable
      materials in endoscopic laser surgery of the upper airway and hypopharynx, the
      risk of tissue ignition remains due to the inflammable laser smog which is easily
      ignited in an oxygen-rich environment. Hence to minimise this risk, we recommend
      using oxygen concentrations lower than 40%, low laser intensities (<6 W) and
      limiting continuous laser activation to periods shorter than 10 s.

PMID- 16432743
TI  - Asymmetric oxidation by Gluconobacter oxydans.
AB  - Asymmetric oxidation is of great value and a major interest in both research and
      application. This review focuses on asymmetric oxidation of organic compounds by
      Gluconobacter oxydans. The microbe can be used for bioproduction of several kinds
      of important chiral compounds, such as vitamin C, 6-(2-hydroxyethyl)amino-6-deoxy
      alpha-L-sorbofuranose, (S)-2-methylbutanoic acid, (R)-2-hydroxy-propionic acid
      and 5-keto-D-gluconic acid. Characteristics of the bacteria and research progress
      on the enantioselective biotransformation process are introduced.

PMID- 16432742
TI  - Pathways and regulation of bacterial arginine metabolism and perspectives for
      obtaining arginine overproducing strains.
AB  - L-arginine is produced by bacterial fermentation and is consumed in food
      flavoring and pharmaceutical industries. A better understanding of arginine
      metabolism in bacteria could be beneficial for a rational design of recombinant L
      arginine producers by genetic engineering. This mini-review illustrated the
      current status of genes and enzymes for arginine metabolism, including
      biosynthetic pathways, catabolic pathways, uptake and excretion systems, and
      regulation. The linkage of polyamine and glutamate metabolism to the arginine
      network was also discussed, followed by a perspective view on how to construct
      arginine overproducing strains of bacteria with increasing biosynthesis and
      excretion and decreasing catabolism and uptake.

PMID- 16432744
TI  - Selenite reduction by a denitrifying culture: batch- and packed-bed reactor
      studies.
AB  - Selenite reduction by a bacterial consortium enriched from an oil refinery waste
      sludge was studied under denitrifying conditions using acetate as the electron
      donor. Fed-batch studies with nitrate as the primary electron acceptor showed
      that accumulation of nitrite led to a decrease in the extent of selenite
      reduction. Also, when nitrite was added as the primary electron acceptor, rapid
      selenite reduction was observed only after nitrite was significantly depleted
      from the medium. These results indicate that selenite reduction was inhibited at
      high nitrite concentrations. In addition to batch experiments, continuous-flow
      selenite reduction experiments were performed in packed-bed columns using
      immobilized enrichment cultures. These experiments were carried out in three
      phases: in phase I, a continuous nitrate feed with different inlet selenite
      concentration was applied; in phase II, nitrate was fed in a pulsed fashion; and
      in phase III, nitrate was fed in a continuous mode but at much lower
      concentrations than the other two phases. During the phase I experiments, little
      selenite was removed from the influent. However, when the column was operated in
      the pulse feed strategy (phase II) or in the continuous mode with low nitrate
      levels (phase III), significant quantities of selenium were removed from solution
      and retained in the immobilization matrix in the column. Thus, immobilized
      denitrifying cultures can be effective in removing selenium from waste streams,
      but nitrate-limited operating conditions might be required.

PMID- 16432745
TI  - The use of deciduous molars in EPR dose reconstruction.
AB  - In the present study naturally loose deciduous molars were investigated. The
      feasibility of separating enamel from small size molars was analysed. EPR
      spectrum parameters of whole molars and separated enamel only were evaluated
      before and after laboratory irradiation. The Electron paramagnetic resonance
      (EPR) signal amplitudes of CO (2) (-) and native signals were determined by
      spectrum deconvolution, as a function of radiation dose in the range 0.1-10 Gy. A
      detection threshold of absorbed dose from deciduous molars of 198 and 21 mGy is
      estimated for massive (that contained both enamel and dentine) and grainy samples
      (that contained enamel only), respectively. The elimination of the organic
      material from the massive deciduous samples reduced the mean bias dose for the
      native signal from 90+/-18 to 34+/-13 mGy. A decay of the background signal
      within 2 weeks after irradiation was found, while the dosimetric signal was
      stable before and after the irradiation process. The presented results suggest
      deciduous teeth to be suitable for retrospective dose assessment. To get
      reasonable dose estimates, however, any organic material must be eliminated, and
      the measurements should be performed 2 weeks after the chemical and mechanical
      preparation and the irradiation process are done.

PMID- 16432746
TI  - Isolation and characterization of Acidicaldus organivorus, gen. nov., sp. nov.: a
      novel sulfur-oxidizing, ferric iron-reducing thermo-acidophilic heterotrophic
      Proteobacterium.
AB  - Thermo-acidophilic prokaryotes isolated from geothermal sites in Yellowstone
      National Park were identified as novel alpha-Proteobacteria, distantly related
      (approximately 93% 16S rRNA gene identity) to the mesophilic acidophile
      Acidisphaera rubrifaciens. One of these isolates (Y008) was shown to be more
      thermophilic than all previously characterized acidophilic proteobacteria, with a
      temperature optimum for growth between 50 and 55 degrees C and a temperature
      maximum of 65 degrees C. Growth was observed in media maintained at pH between
      1.75 and 3.0 and was fastest at pH between 2.5 and 3.0. The G + C content of Y008
      was 71.8+/-0.9 mol%. The acidophile was able to grow heterotrophically on a range
      of organic substrates, including various monosaccharides, alcohols and amino
      acids and phenol, though growth on single organic compounds required the
      provision of one or more growth factors. The isolate oxidized sulfur to sulfuric
      acid in media containing yeast extract, but was not capable of autotrophic growth
      with sulfur as energy source. Growth occurred under aerobic conditions and also
      in the absence of oxygen via anaerobic respiration using ferric iron as terminal
      electron acceptor. Based on these genotypic and phenotypic traits, it is proposed
      that Y008 represents the type species of Acidicaldus organivorus, gen. nov., sp.
      nov.

PMID- 16432747
TI  - Plasma membrane of Synechocystis PCC 6803: a heterogeneous distribution of
      membrane proteins.
AB  - Proteomic studies carried out previously on the plasma membrane of Synechocystis
      have identified several peripheral and integral proteins. The distribution of
      these proteins along the membrane still remains obscure. In this study, the
      distribution of proteins along the plasma membrane of Synechocystis was carried
      out using subfractions, the right-side-out (RSO) and inside-out (ISO) vesicles,
      fractionated from a pure and specific fraction of the plasma membrane. These
      subfractions were analyzed and quantified for several proteins by immunoblotting.
      It was found that the ISO fraction contained higher quantities of preD1, D1 and
      PsaD, the integral proteins of photosystem I and II known to be present also in
      the plasma membrane. Lower amounts of peripheral vesicle inducing protein Vipp1
      and nitrate/nitrite binding protein NrtA were present in the ISO compared to the
      RSO fraction. On the contrary, the distribution of two integral transporter
      proteins, SbtA and PxcA, was found equal in both fractions. Our studies clearly
      establish that the plasma membrane of Synechocystis has a heterogeneous
      composition with respect to protein distribution. The accumulation of
      photosynthesis-associated proteins in the ISO fraction provides evidence that the
      discrete regions of the plasma membrane harbor sites for biogenesis of
      photosystems.

PMID- 16432748
TI  - Degradation of and sensitivity to cholate in Pseudomonas sp. strain Chol1.
AB  - A facultative anaerobic bacterium, Pseudomonas sp. strain Chol1, degrading
      cholate and other bile acids was isolated from soil. We investigated how strain
      Chol1 grew with cholate and whether growth was affected by the toxicity of this
      compound. Under anoxic conditions with nitrate as electron acceptor, strain Chol1
      grew by transformation of cholate to 7,12-dihydroxy-1,4-androstadiene-3,17-dione
      (DHADD) as end product. Under oxic conditions, strain Chol1 grew by
      transformation of cholate to 3,7,12-trihydroxy-9,10-seco-1,3,5(10)-androstatriene
      9,17-dione (THSATD), which accumulated in the culture supernatant before its
      further oxidation to CO(2). Strain Chol1 converted DHADD into THSATD by an
      oxygenase-dependent reaction. Addition of cholate (> or =10 mM) to cell
      suspensions of strain Chol1 caused a decrease of optical density and viable
      counts but aerobic growth with these toxic cholate concentrations was possible.
      Addition of CCCP or EDTA strongly increased the sensitivity of the cells to 10 mM
      cholate. EDTA also increased the sensitivity of the cells to DHADD and THSATD (<
      or =1.7 mM). The toxicity of cholate and its degradation intermediates with a
      steroid structure indicates that strain Chol1 requires a strategy to minimize
      these toxic effects during growth with cholate. Apparently, the proton motive
      force and the outer membrane are necessary for protection against these toxic
      effects.

PMID- 16432749
TI  - Cervical vertigo and dizziness after whiplash injury.
AB  - Whiplash injury is not only limited to neck injury but also brainstem injury that
      does not involve direct damage to the neck or head. The symptoms of whiplash
      injury are polymorphous, with the most common complaints being cervical pain,
      headache and scapulodynia. Vertigo and dizziness are also reported in 25-50% of
      the cases. In otoneurologic studies, magnetic resonance angiography (MRA) is used
      for the evaluation of vertebrobasilar hemodynamics in patients who complain of
      dizziness and vertigo. It is reported that vertebrobasilar artery insufficiency
      (VBI) leads to brainstem and cerebellar ischemia and infarction following
      cervical manipulation. Here we examined the correlation between vertigo or
      dizziness and the right and left side difference in vertebral arteries after
      whiplash injury using MRA. We studied 20 patients who complained of neck pain
      with vertigo or dizziness after whiplash injury and 13 healthy volunteers as a
      control. In the control group, abnormal MRA findings in the vertebral arteries
      such as occlusion, stenosis or slow blood flow were seen in 77% of the cases. In
      the patient group, abnormal MRA findings were seen in 60%. The side difference in
      blood flow was 3.5+/-2.5 cm/s in the control group and 6.1+/-3.0 cm/s in the
      patient group. Our findings suggest that some subjects with persistent vertigo or
      dizziness after whiplash injury are more likely to have VBI on MRA. VBI might be
      an important background factor to evoke cervical vertigo or dizziness after
      whiplash injury. The side difference between the two vertebral arteries could
      cause a circulation disorder in the vertebrobasilar system after whiplash injury.
      However, the VBI on MRA itself was also seen in the control group, and thus it is
      not clear whether it is due to whiplash injury in the patient group.

PMID- 16432751
TI  - [A surgical approach to acute intestinal bleeding].
AB  - The estimated incidence of lower gastrointestinal bleeding (LGIB) is 20/100,000
      patients per year. Of these cases, 70-80% are minor or stop spontaneously and do
      not present as emergency hospital admissions. Colonoscopy and angiography detect
      80-90% of major LGIB, and subsequent endoscopic intervention or embolisation can
      control approximately 70%. Emergency surgical intervention is required in
      haemodynamically unstable patients with persistent bleeding. The surgical
      treatment of choice is directed to resecting the bleeding bowel segment. Subtotal
      colectomy is performed in patients with colonic bleeding that can not exactly be
      localized. Segmental colon resection is often associated with rebleeding and not
      recommended in this situation. Primary anastomosis can usually be performed;
      elderly patients in reduced condition, however, are candidates for stoma. In case
      of persistent or recurrent bleeding and differentiation between intestinal and
      colonic bleeding fails, loop ileostomy may be performed. If the bleeding appears
      to originate from somewhere in the small bowel, an additional loop jejunostomy
      may be performed for specification. The mortality from acute LIGB is
      approximately 5% but increases with emergency surgery. Risk factors are age,
      comorbidity, and shock on admission.

PMID- 16432752
TI  - [Chronic fistulas with impaired wound healing].

PMID- 16432750
TI  - Occupations associated with a high risk of self-reported back pain:
      representative outcomes of a back pain prevalence study in the Federal Republic
      of Germany.
AB  - Given the increasing medical and economic implications of back pain, occupation
      specific prevalence data may provide important pointers for preventive programmes
      targeted at promoting preventive behaviour and improving conditions. The National
      German Health Survey is the first study to provide the basis for a representative
      nationwide analysis of back pain prevalence by occupational category. The net
      sample comprises a total of 3,488 earners aged 18-69. One in three earners in the
      Federal Republic of Germany (34%) experienced back pain during the 7 days prior
      to being interviewed. The 1-year prevalence rate is 60%. Occupational categories
      associated with a lower-than-average back pain prevalence are highly qualified
      professionals, senior management, and production occupations associated with a
      comparatively low degree of manual labour. In contrast, an above-average
      prevalence was identified for occupations associated with physically strenuous
      work involving one-sided postures, moving, carrying and holding heavy weights,
      and work typically performed in poor conditions or bad weather. Our data
      demonstrates significant inter-occupational differences in terms of self-reported
      back pain. The results underline the importance of measures to promote preventive
      behaviour and improve the working conditions of those in low-skill manual labour
      occupations.

PMID- 16432753
TI  - [Vascular anomalies of the cerebellopontine angle].
AB  - Vascular anomalies of the cerebellopontine angle are rare compared to tumors in
      this area. Irritation of the trigeminal, facial, or vestibulocochlear nerve may
      cause trigeminal neuralgia, hemifacial spasm and vertigo, or tinnitus
      accordingly. Vessel loops in the cerebellopontine cisterns may cause compression
      at the root entry or exit zone of the cranial nerves V, VII, and VIII, a
      phenomenon which is called "vascular loop syndrome." Megadolichobasilar artery
      and aneurysms of the vertebrobasilar system can also lead to dislocation and
      compression of the cranial nerves and brain stem. Three-dimensional CISS MR
      imaging and MR angiography are useful in the detection of neurovascular
      compression. Microvascular decompression is an effective surgical procedure in
      the management of compression syndromes of the cranial nerves V, VII, and VIII.

PMID- 16432754
TI  - Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces
      protection in mice against Leishmania (Leishmania) major infection.
AB  - Heat shock proteins (HSPs) are highly conserved among different organisms. A
      mycobacterial HSP65 DNA vaccine was previously shown to have prophylactic and
      immunotherapeutic effects against Mycobacterium tuberculosis infection in mice.
      Here, BALB/c mice were immunized with mycobacterial DNA-hsp65 or with DNA-hsp65
      and trehalose dymicolate (TDM), both carried by biodegradable microspheres
      (MHSP/TDM), and challenged with Leishmania (Leishmania) major. MHSP/TDM conferred
      protection against L. major infection, as indicated by a significant reduction of
      edema and parasite loads in infected tissues. Although high levels of interferon
      gamma and low levels of interleukin (IL)-4 and IL-10 were detected in mice
      immunized with DNA-hsp65 or MHSP/TDM, only animals immunized with MHSP/TDM
      displayed a consistent Th1 immune response, i.e., significantly higher levels of
      anti-soluble Leishmania antigen (SLA) immunoglobulin G (IgG)2a and low anti-SLA
      IgG1 antibodies. These findings indicate that encapsulated MHSP/TDM is more
      immunogenic than naked hsp65 DNA, and has great potential to improve vaccine
      effectiveness against leishmaniasis and tuberculosis.

PMID- 16432756
TI  - Martin Allgower, Professor Dr med, Dres med hc mult, Emeritus Chair and Professor
      of Surgery, University of Basle, Switzerland.

PMID- 16432755
TI  - Intestinal parasitism in Peruvian children and molecular characterization of
      Cryptosporidium species.
AB  - Intestinal parasitism was studied in children of Trujillo (Peru) to create a
      prevention and control program. Fecal samples of 489 children were examined. The
      general prevalence of intestinal parasitosis was found to be 68%. The most
      frequent pathogenic enteroparasites were Giardia lamblia (26.4%), Cyclospora
      cayetanensis (13%), Hymenolepis nana (2%), Hymenolepis diminuta (1.6%), and
      Cryptosporidium spp. (1%). All these parasites appeared both in diarrheic and
      nondiarrheic children, except Cryptosporidium, which invariably caused diarrhea.
      Multiple parasitism was frequent, 45.6% of the children presenting two, three, or
      four intestinal parasites. Cryptosporidium was the only parasite that was not
      associated with the others. Only five children were affected of
      cryptosporidiosis, presenting explosive diarrhea, nausea, and vomiting.
      Cryptosporidium species and genotypes involved in the infantile cryptosporidiosis
      were determined by polymerase chain reaction-restriction fragment length
      polymorphism. Four children were parasitized by Cryptosporidium hominis and only
      one by Cryptosporidium parvum. Our results confirm that anthroponotic
      transmission of Cryptosporidium is predominant in Peru.

PMID- 16432757
TI  - Influence of UPPP surgery on tolerance to subsequent continuous positive airway
      pressure in patients with OSAHS.
AB  - To investigate the effect of uvlopalatopharyngoplasty (UPPP) on post-surgery
      continuous positive airway pressure (CPAP) treatment during sleep in patients
      with obstructive sleep apnea-hypopnea syndrome (OSAHS). Thirty-one OSAHS patients
      after UPPP surgery were recruited and studied on for more than 12 months after
      the procedure. Among them, 24 patients were treated with classical UPPP (cUPPP),
      which removes all of uvula and part of the soft palate. Seven had modified UPPP
      (mUPPP), keeping part of the uvula. The control group was 31 years in age, body
      mass index (BMI) and apnea-hypopnea index (AHI) matched, and newly diagnosed
      OSAHS patients without prior treatment. A manual titration of CPAP was performed
      during both (NREM) and non-rapid eye movement (NREM) sleep in all 62 patients.
      Patients were asked to keep a supine position while sleeping during the test.
      When significant mouth air leakage occurred and/or titration worsened with an
      increase of CPAP pressure, the pressure level was considered as the highest CPAP
      (hCPAP) a patient can tolerate in that sleep stage. The CPAP machine used for
      titration could produce highest pressure at 20 cm H2O. There were 74% (23/31) of
      UPPP patients who had less than 50% decrease in AHI, and 84% (26/31) of the 31
      patients still had AHI>15 (range 16-110) during post-operation polysomnography
      (PSG) test. Most of them need further CPAP therapy. All of the untreated OSAHS
      patients could tolerate 17-20 cm H2O of CPAP during sleep. None had severe mouth
      air leak before an optimal pressure was reached. In contrast, four in the surgery
      group failed to respond to CPAP treatment during both NREM and REM sleep and one
      more during REM sleep. All of the seven patients who had a mUPPP could tolerate
      CPAP. One of the three tested both before and after surgery failed in the CPAP
      treatment after surgery during REM sleep. UPPP may compromise nasal CPAP therapy
      in OSAHS, especially in procedures with greater resection of the soft palate.

PMID- 16432758
TI  - Differential interaction of magnetic nanoparticles with tumor cells and
      peripheral blood cells.
AB  - PURPOSE: The separation of tumor cells from healthy cells is a vital problem in
      oncology and hematology, especially from peripheral blood. Magnetic assisted cell
      sorting (MACS) is a possibility to fulfill these needs. METHODS: Tumor cell lines
      and leukocytes from peripheral blood were incubated with carboxymethyl dextran
      coated magnetic nanoparticles under various conditions and separated by MACS.
      RESULTS: We studied the interaction of magnetic nanoparticles devoid of
      antibodies with healthy and tumor cells. The magnetic nanoparticles interact with
      tumor cells and leukocytes and are located predominantly within the cell
      cytoplasm. Incubation of cell culture cells with magnetic nanoparticles led to a
      labeling of these cells without reduced biological properties for at least 14
      days. The interaction of the magnetic nanoparticles with cells depends on several
      factors. The ionic strength (osmolality) of the solvent plays an important role.
      We could show that an increase in osmolality led to a dramatic reduction of
      labeled leukocytes. Tumor cells, however, are mildly affected. This could be
      detected not only in pure cultures of tumor cells or leukocytes but also in mixed
      cell populations. CONCLUSION: This observation gives us the opportunity to
      selectively label and separate tumor cells but not leukocytes from the peripheral
      blood.

PMID- 16432760
TI  - The effect of repeated tryptophan administration on body weight, food intake,
      brain lipid peroxidation and serotonin immunoreactivity in mice.
AB  - Tryptophan as a circulating precursor of serotonin (5-HT) may suppress food
      intake and body weight. Tryptophan administration can enhance the generation of
      reactive oxygen species (ROS) by inducing oxidative pathway in vivo and in vitro.
      We have examined the effect of repeated tryptophan administration on food
      consumption, body weight, brain lipid peroxidation and 5-HT immunoreactivity.
      Tryptophan was given at the dose of 100 mg/kg/24 hr in 0.2 ml saline solution
      i.p. for 7 days to mice. Control mice received 0.9% NaCL solution at the same
      manner and volume. Body weights were recorded at the beginning and end of the
      experiments. Thiobarbituric acid reactive substance (TBARS), the last product of
      lipid peroxidation, was measured spectrophotometrically. Brain 5-HT levels were
      determined by the immunohistochemical method. Our findings indicate that the
      tryptophan suppresses food intake significantly in mice. Body weight decreased
      and brain TBARS levels increased significantly by repeated tryptophan treatment.
      Immunohistochemical detection showed that 5-HT levels increased by tryptophan
      administration. There is a link between increased 5-HT level and oxidative stress
      by tryptophan administration on brain tissue. Tryptophan at repeated doses should
      be exercised carefully in clinical practice.

PMID- 16432761
TI  - Causal relationship between hexachlorocyclohexane cytotoxicity, oxidative stress
      and Na+, K +-ATPase in Ehrlich Ascites tumor cells.
AB  - Role of oxidative stress and Na+,K+-ATPase in the cytotoxicity of
      hexachlorocyclohexane (HCH) on Ehrlich Ascites tumor (EAT) cells has been
      studied. HCH caused dose dependent cell death as measured by trypan blue
      exclusion and lactate dehydrogenase (LDH) leakage from the cells. HCH induced
      oxidative stress in EAT cells which was characterized by glutathione depletion,
      lipid peroxidation (LPO), reactive oxygen species (ROS) production and inhibition
      of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Protective
      effect of antioxidants on HCH induced oxidative stress was assessed, among the
      antioxidants used only quercetin inhibited HCH-induced LPO and ROS production as
      well as cell death whereas alpha -tocopherol, ascorbic acid and BHA inhibited LPO
      but not cell death. Inhibition of membrane bound Na+,K+-ATPase was a
      characteristic feature of HCH cytotoxicity in EAT cells. Experimental evidence
      indicates that HCH-induced cell death involves oxidative stress due to ROS
      production and membrane perturbation in EAT cells.

PMID- 16432763
TI  - The sensitive fluorimetric method for the determination of curcumin using the
      enhancement of mixed micelle.
AB  - Curcumin (C21H20O6) is a natural antioxidant, which is considered to be a very
      useful compound in health matters, and is employed in the treatment of
      cardiovascular and arthritic illnesses. It is found that the fluorescence of
      curcumin is greatly enhanced by mixed micelle of sodium dodecyl benzene sulfonate
      (SDBS) and cetyltrimethylammonium bromide (CTAB) surfactants. Based on this, a
      sensitive fluorimetric method for the determination of curcumin in aqueous
      solution is proposed. In the HOAc-NaOAc buffer, the fluorescence intensity of
      curcumin is proportional to the concentration of curcumin in the range of 0.00020
      0.74 microg/mL and the detection limit is 0.017 ng/mL. The synthetic and actual
      samples are satisfactorily determined. In addition, the interaction mechanism is
      also studied.

PMID- 16432762
TI  - Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of
      interaction with XIAP.
AB  - XIAP-associated factor 1 (Xaf1) binds XIAP and re-localizes it to the nucleus,
      thus inhibiting XIAP activity and enhancing apoptosis [1]. Xaf1 expression is
      reduced or absent in tumor samples and cell lines suggesting it may function as a
      tumor suppressor [2-5]. To further study Xaf1 function we generated Xaf1
      inducible cells in the osteosarcoma cell line Saos-2. Despite Xaf1 inducing
      apoptosis that is dramatically enhanced by TNFalpha we find no evidence for an
      interaction between Xaf1 and XIAP. Furthermore, Xaf1 expression sensitized XIAP-/
      fibroblasts to TNFalpha, demonstrating the existence of a novel mechanism of
      Xaf1 induced apoptosis distinct from antagonizing XIAP. Xaf1 expression promotes
      cytochrome c release that cannot be blocked by inhibition of caspase activity.
      This implicates a role for the mitochondrial apoptotic pathway, consistent with
      the ability of Bcl2 to block Xaf1 induced apoptosis. The data indicate that in
      Saos2 cells Xaf1 activates the mitochondrial apoptotic pathway to facilitate
      cytochrome c release, thus amplifying apoptotic signals from death receptors.

PMID- 16432764
TI  - Language acquisition is language change.
AB  - According to the theory of Universal Grammar, the primary linguistic data guides
      children through an innately specified space of hypotheses. On this view,
      similarities between child-English and adult-German are as unsurprising as
      similarities between cousins who have never met. By contrast, experience-based
      approaches to language acquisition contend that child language matches the input,
      with nonadult forms being simply less articulated versions of the forms produced
      by adults. This paper reports several studies that provide support for the theory
      of Universal grammar, and resist explanation on experience-based accounts. Two
      studies investigate English-speaking children's productions, and a third examines
      the interpretation of sentences by Japanese speaking children. When considered
      against the input children are exposed to, the findings of these and other
      studies are consistent with the continuity hypothesis, which supposes that child
      language can differ from the language spoken by adults only in ways that adult
      languages can differ from each other.

PMID- 16432766
TI  - [Psychosocial adjustment, relationship and self-concept in siblings of children
      with idiopathic epilepsy syndromes].
AB  - BACKGROUND: Psychosocial adjustment, relationship and self-concept in siblings of
      children with idiopathic epilepsy was compared with healthy controls. PATIENTS:
      173 persons--68 siblings, 62 mothers and 43 fathers--from the study group
      (children with idiopathic epilepsy) and matched controls were investigated.
      METHODS: Child Behaviour Checklist (CBCL), Self-Description-Questionnaire I and
      II (SDQ) and Sibling Relationship Questionnaire (SRQ) were used. RESULTS: There
      were more somatic complaints of the siblings reported by the mothers of the study
      group. They also noted more nurturance of the sibling than mothers of healthy
      children did. The data of the fathers showed more dominance of the sibling.
      Siblings of children with epilepsy showed more prosocial action towards their
      classmates. In families with a new diagnosed epilepsy the fathers noticed more
      problems in school und somatic complaints of the siblings. The number of
      seizures, which were seen by the sibling, not the absolute number of seizures,
      had an influence on the behavior of the siblings; these siblings had more social
      problems than siblings, who had never seen a seizure. CONCLUSIONS: We suggest a
      close cooperation with the families and constant inclusion in the treatment as
      claimed by recent systemic family medicine. Resource-orientated and salutogenetic
      aspects should be given a greater focus in modern work with families and
      especially siblings.

PMID- 16432767
TI  - [Quality of life with cystic fibrosis--aspects of age and gender].
AB  - BACKGROUND: Quality of life (QoL) becomes more important as primary criterion of
      quality management in time consuming therapy programs of chronic progressive
      diseases like cystic fibrosis (CF). Measuring weighted satisfaction of life
      allows to evaluate subjective aspects of health-related and general quality of
      life. PATIENTS/METHOD: QoL of 254 CF-patients (age 16-45 years, mean 29.4 years,
      mean FEV1 62.5 % of the predicted, mean BMI 20.5) was evaluated with the
      Questions on Life Satisfaction (FLZ(M)), a multi-dimensional QoL questionnaire.
      QoL results of patients are compared with the QoL of a healthy population.
      RESULTS: Subjective contentment in health-related life dimensions of German
      adolescents and adults with CF is significantly lower compared with healthy
      peers. Women with CF compensate their increased restriction in health-related
      dimensions by high satisfaction in the dimensions housing and partnership. Women
      with CF > 35 years have a risk for low life satisfaction, men of this age group
      are not restricted. CONCLUSIONS: Therapy programs should take into account the
      subjective perceived QoL. Routine monitoring of QoL can indicate patients with
      special needs.

PMID- 16432768
TI  - [Extrathoracal pulmonary sequestration in the differential diagnosis of
      paravertebral tumors in the neonate].
AB  - BACKGROUND: Paravertebral masses of the fetus are often detected during routine
      prenatal ultrasonography. The most common differential diagnoses of these tumors
      are neuroblastoma, adrenal hemorrhage, schwannoma and germ cell tumors. CASE
      REPORT: We report on a mature male newborn, who was diagnosed antenatally at 23 +
      3 weeks of gestation with a tumor in the left paravertebral region. After birth
      the child was transferred to a neonatal unit. Tumor markers like urinary
      catecholamines were within normal limits, neuron-specific enolase was slightly
      elevated. MRI as well as ultrasonography confirmed a 3.2 x 2.2 x 1.6 cm large
      smoothed edged tumor in the left paravertebral region at the level of T10-T12. An
      open biopsy was performed, and the tumor which was located below the diaphragma
      was subtotally resected. Histopathology showed an extralobar pulmonary
      sequestration. Surgery as well as postoperative course was uneventful.
      CONCLUSIONS: Extralobar pulmonary sequestrations represent rare congenital
      anomalies, which are usually asymptomatic. Clear differentiation between tumor
      and pulmonary sequestration is seldom possible despite high resolution imaging
      studies. Hence, a biopsy procedure should be done for diagnosis of paravertebral
      masses.

PMID- 16432769
TI  - [Circulatory failure due to severe cardiac arrhythmia as a result of hyperkalemia
      in a very low birth weight infant].
AB  - BACKGROUND: Hyperkalemia is frequently seen during the first days of life in
      premature infants with a gestational age at birth less than 28 weeks. Normally,
      these high concentrations of potassium are well tolerated of the premature
      infants. In a few cases hyperkalemia leads to life-threatening cardiac
      arrhythmias. CASE REPORT: We report about a 800 grams weighing preterm infant
      born after 26 + 4 gestational weeks. 24 hours after birth the infant developed 2
      : 1 atrioventricular block due to hyperkalemia with a heart rate about 75 bpm.
      The bradycardia continued about 45 minutes in spite of immediate therapy
      concomitant by circulatory failure that resulted in an intraventricular
      hemorrhage of grade III with periventricular intraparenchymal lesions.
      CONCLUSIONS: The case report demonstrates the variations of the electrocardiogram
      that can be found in preterm infants with hyperkalemia and their potential risks.
      Therapy of symptomatic hyperkalemia is not able to interrupt early a life
      threatening circulatory failure in any case.

PMID- 16432770
TI  - [Wegener's granulomatosis as a rare cause of hemoptysis in childhood].
AB  - Wegener's granulomatosis is together with Churg-Strauss syndrome and microscopic
      polyangiitis a very rare cause of hemoptysis in childhood. We report on a 14
      years old girl who developed arthralgia, purpura, glomerulonephritis and a
      diffuse alveolar haemorrhage with hemoptysis after a short time period of
      unspecific symptoms.

PMID- 16432771
TI  - [Rare case of an epidemiologically important tuberculosis in childhood].
AB  - BACKGROUND: Tuberculosis is an infectious disease which is nearly forgotten in
      Germany because of its low incidence. CASE REPORT: We report on a 14-year-old
      german girl who was disregarded when active case-finding of her uncle's active
      pulmonary tuberculosis was carried out three years before. As a result she
      herself developed a severe infectious pulmonary tuberculosis. The delay between
      onset of symptoms and diagnosis gives cause for concern and led to active
      tuberculosis in her brother and her girl friend as well. The lack of information
      about tuberculosis in population and delay of medical detection in this case led
      unnecessarily to the continuing chain of infection. CONCLUSIONS: This case report
      shows that there are severe infectious courses of tuberculosis even in childhood
      which might get epidemiologically important. For earlier diagnosis and successful
      interruption of chains of infection tuberculosis in the German population even
      today has to be taken into account. Case detection through contact investigation
      of adults is of great importance in childhood and adolescence.

PMID- 16432772
TI  - [Exudative enteropathy in congenital lymphedema-lymphangiectasia syndrome].
AB  - BACKGROUND: Congenital peripheral elephantiasiformic alterations are very rare in
      paediatric patients. In a patient with lymphangiectasia-lymphedema syndrome we
      demonstrate over a 8-year follow-up that not only cosmetic and social indications
      for surgical treatments but also internal care become important during the
      course. PATIENT: We report on a boy with congenital lymphedemas of the
      extremities and the genital region, which were several times surgically treated.
      The patient became symptomatic firstly with tetanic cramps caused by
      malabsorption syndrome due to intestinal lymphangiectasia at the age of 6 years.
      Synopsis of clinical and laboratory findings and the patient's course are
      pointing to a mild Hennekam syndrome with still unknown aetiology. RESULTS: The
      boy developed adequately with permanent oral substitution of electrolytes and
      vitamins, protein-rich diet, supplementation of medium-chain fatty acids and
      compressing bandages. Infusions of human albumin to correct persistent
      hypalbuminemia as well as cytostatic treatment with cyclophosphamide as a formal
      trial were ineffective and are not advisable, therefore.

PMID- 16432773
TI  - [Drug poisonings in childhood at a regional poisons unit].
AB  - BACKGROUND: Drug poisonings in childhood account with about one fourth for the
      most important group of poisonings in this age group. METHOD: From 1995 to 2004
      the inquiries to a poison centre regarding drug poisonings of children < or = 6
      years of age were analyzed. Additionally, a standardized questionnaire was sent
      for follow-up information. RESULTS: During the study period a total number of 17
      553 cases of drug poisonings in childhood was determined and follow-up
      information was obtained for 8 590 cases (48.9 %). Boys were more likely to be
      affected (53.4 %) and most children were between 2 and 4 years of age (57.5 %).
      Mostly oral contraceptives, homeopathic drugs, nonsteroidal anti-inflammatory
      drugs, sodium fluoride and paracetamol were ingested. In 97.8 % of the reported
      cases none or minor symptoms and in 1.5 % medium or major symptoms (1 death) were
      observed. In the latter group of patients mostly neuroleptics, antihistaminics,
      nonsteroidal anti-inflammatory drugs, beta2-sympathomimetics and paracetamol were
      ingested. In most cases the application of fluids (47.3 %) or activated charcoal
      (32.0 %) was sufficient. CONCLUSIONS: Severe symptoms have rarely been observed
      in drug poisonings and in most children a treatment by non-professionals was
      sufficient. Most frequently activated charcoal was currently used for primary
      poison elimination. We suggest an early involvement of a poison centre in drug
      intoxications.

PMID- 16432774
TI  - [Attempted suicide with L-thyroxine in an adolescent girl].
AB  - BACKGROUND: Attempted suicide with l-thyroxine (LT4) is very rare, only being
      published in some case reports concerning young women. Experiences in the
      management of LT4 intoxication have already been made because overdosage in
      infants occurs more often. Guidelines and recommendations depend on the quantity
      of LT4 that has been ingested. PATIENT: A 17-year-old girl presented to the
      pediatric emergency department after intentional ingestion of 20 mg of LT4 20
      hours prior to admission. Anamnestically she had increased the thyroxine dose
      rate up to 800 microg per day during the previous 4 months in order to obtain
      loss of weight. In spite of massive overdosage and extremely high serum thyroxine
      levels (fT4 794 pg/ml, TSH suppressed) the girls showed low symptoms and a mild
      clinical course. Because of tachycardia, hyperhidrosis and muscle tremor
      propranolol was applied. During the following 22 days fT4 levels returned to
      normal range and the adolescent was remitted to the outpatient clinic of the
      department of psychiatry. Whereas patients with graves disease and
      thyreotoxicosis present with severe symptoms our patient showed a mild clinical
      course in spite of having extremely high fT4 levels. CONCLUSIONS: The reasons are
      ambiguous. A possible answer could be an adaptation in higher fT4 levels in cause
      of the reported chronic LT4 overdosage.

PMID- 16432775
TI  - [Fabry disease--a provocation for pediatrics].
AB  - Fabry disease is an inherited metabolic disease caused by the deficiency of the
      lysosomal enzyme alpha-Galactosidase A. In consequence, globotriaosylceramide
      (Gb3) accumulates in nearly all tissues and body fluids. Typically, the disease
      manifestation is in childhood with acroparaesthesia of burning character in hands
      and feet. Angioceratoma, cornea verticillata and proteinuria may be found as well
      at an early stage of the disease. With ongoing age vital organs are increasingly
      affected. Major causes for death are cerebrovascular events, myocardial
      infarction, and progressive renal insufficiency. Enzyme replacement therapy (ERT)
      offers an efficient treatment of Fabry disease. On the basis of newly diagnosed
      patients we describe the clinical picture, diagnosis and principles of ERT.

PMID- 16432776
TI  - [Dermatitis and eosinophilia in a 9-year-old girl from Congo: putative
      onchodermatitis].
AB  - Onchocercosis or riverblindness, caused by the filaria ochnocerca volvulus, is
      endemic in many countries of central and Western Africa. Symptoms of the disease
      can occur years after the infection, chronic itching dermatitis is the first
      sign, without treatment blindness may develop after years. Onchodermatitis is a
      hyperreactive course of onchocercosis with massive eosinophilia and elevated IgE,
      which suppresses a microfilarial spread through the body. Here, we report about
      the case of an 9-year-old girl who immigrated from the republic of Congo at the
      age of seven and has been living in Germany for more than two years. Presumably
      she suffered from onchodermatitis. She presented papular, indurated and itching
      skin lesions with pigmentary changes, predominantly located at the limbs.
      Remarkable results of blood tests were 11,000/microl (60 %) eosinophils and IgE
      28 000 KU/l, ECP > 200 mg/l, without a history of atopic diseases. HIV,
      Strongylosis and Loa Loa were excluded. Anti filaria antibodies were detected in
      a concentration of 51 AKE, microscopy of skin samples failed to detect the
      parasites. After a single dose of Ivermectin the dermatitis improved, after two
      weeks the itching was absent, results of repeated blood tests tend to normalize
      in the following months. Due to the long lifespan of filaria in humans, the
      disease occurs years after infection in endemic areas. The differential diagnosis
      for itching skin lesions with high eosinophils in children from developing
      countries should include onchocercosis.

PMID- 16432777
TI  - Calcific tendinitis of the supraspinatus tendon in children.
AB  - We present the case of a 13-year-old girl with painful calcific tendinitis of the
      supraspinatus tendon of the left shoulder. The pathologic finding was the
      presence of a small calcium deposit within the supraspinatus tendon.
      Pediatricians should be aware of this entity in shoulder pain in children.

PMID- 16432778
TI  - Association of motor deficits with head position during awake surgery for
      resection of medial motor area brain tumors.
AB  - OBJECTIVE: Resection of tumors involving the motor area frequently results in
      postoperative motor deficits. In an attempt to prevent poor motor outcomes, our
      institution has utilized preoperative fMRI and tractography as well as
      intraoperative cortical mapping and continuous motor tasks during awake surgery
      in patients with motor area tumors. In one case, a patient demonstrated
      deterioration in continuous motor task performance before initiation of tumor
      resection. Thus, the goal of this study was to evaluate the relationship between
      head position and development of intraoperative or postoperative motor deficits
      in five patients with motor area tumors. CLINICAL PRESENTATION: In four cases,
      the patient's head was rotated 60 degrees from the supine position. In two cases,
      in which the tumor was located relatively medially, deterioration in continuous
      motor task function was noted prior to resection of the tumor. In the two other
      cases, in which the tumor was located relatively laterally, there was no
      deterioration of continuous motor task performance until resection of the tumor.
      Another patient, in whom the tumor was located relatively medially, underwent
      surgery with the head positioned straight and with the patient in a half-sitting
      position. This patient did not experience deterioration of continuous motor task
      performance during the surgery. CONCLUSION: These data suggest that head
      positioning can have a significant impact on motor function in patients with
      motor area tumors. Furthermore, the straight head position may be the preferred
      positioning, particularly for patients with tumors located on the medial side of
      motor area.

PMID- 16432779
TI  - Minimally invasive management of ependymoma of the aqueduct of Sylvius:
      therapeutic considerations and management.
AB  - A major concern in the neuroendoscopic approach to an intraventricular tumor is
      the histological confirmation from a limited biopsy. However, the effort to
      excise the whole bulk of the tumor should be made for the minimally invasive
      management of selected intraventricular tumors. The case of an adult male with
      focal aqueductal ependymoma who presented with the clinical syndrome of
      hydrocephalus is reported. This may be of particular interest because it
      represents the first case of aqueductal ependymoma that has been successfully
      treated with endoscopic surgery.

PMID- 16432780
TI  - Treatment of ruptured intracranial aneurysms: our approach.
AB  - OBJECTIVE: Subarachnoid hemorrhage (SAH) often results in devastating
      neurological deficits requiring hospitalization and loss of independence. This is
      often a difficult time for patients and their families who are struggling to cope
      with this sudden illness. Current treatment options include surgical clipping of
      the aneurysm or endovascular obliteration using Guglielmi detachable coils. Our
      purpose in writing this paper was to review the factors that determine the choice
      of treatment. In addition to this we wanted to study the benefits of surgical
      clipping for ruptured aneurysms over endovascular coiling. MATERIAL AND METHODS:
      We studied--retrospectively--450 cases of ruptured cerebral aneurysms admitted to
      our institution from 1997 to 2003. Out of these, 324 were subjected to surgical
      clipping and 126 to endovascular techniques. The outcome was studied using the
      Glasgow Outcome Score (GOS). RESULTS: Of the 324 cases of surgical clipping 222
      had a good recovery, 38 had moderate disability, 15 had severe disability, 13
      became vegetative and 36 patients died. In the endovascular group 34 had a good
      recovery, 22 had moderate disability, 18 had severe disability, 15 became
      vegetative and 37 patients died. Grade to Outcome was compared for both forms of
      treatment. In our series clipping for ruptured aneurysm was preferred to coiling
      in fusiform-shaped aneurysms, large or giant aneurysms, MCA aneurysms, blister
      aneurysms, complex configurations, partially thrombosed aneurysms and aneurysms
      associated with cerebral hemorrhage. Coiling was performed for basilar tip and
      trunk aneurysms, high anterior communicating artery aneurysms, patients in
      subacute stages of subarachnoid hemorrhage, and those with associated medical
      complications. CONCLUSION: Based on this study we were able to formulate a few
      definite indications for clipping, even in the times of advanced endovascular
      techniques. In addition we could also prove the benefits of surgical clipping
      over the endovascular technique in severe subarachnoid hemorrhage.

PMID- 16432781
TI  - Percutaneous posterior lumbar interbody fusion using the B-twin expandable spinal
      spacer.
AB  - Sixty-two suitable subjects (mean age: 49.3 years) underwent percutaneous
      posterior lumbar interbody fusion (PPLIF) using the B-Twin expandable spinal
      spacer (B-Twin ESS) and were followed thereafter for 2 years or longer. The
      clinical outcome was expressed by the change in pain intensity as scored on a
      visual analogue scale and the change in degree of disability as scored by the
      Oswestry Disability Index. The results were compared with those of a previous
      trial of PLIF using the B-Twin ESS in which the latter was introduced via the
      open surgical approach (OPLIF). Mean duration of operation was 103 minutes. Blood
      loss was negligible. No operative difficulties or complications were encountered.
      No participant was lost to follow-up. Disc space height had increased by a mean
      of 10 %. At that time there were no radiographic signs of non-union in any
      patient. The mean pain intensity and disability scores decreased by 66 % and 61
      %, respectively, as compared to those on admission. The clinical outcome of the
      percutaneous method was comparable to that of the open procedure using the B-Twin
      ESS; however, the results can be interpreted as favoring the former in the
      context of minimal invasiveness. Should this outcome be validated in further
      trials, the technique may be adopted in selective cases.

PMID- 16432782
TI  - Malignant progression of benign brain tumors after gamma knife radiosurgery: is
      it really caused by irradiation?
AB  - Malignant transformation of benign neoplasm after radiosurgery is usually
      diagnosed based on the initial presence of benign tumor, its exposure to ionizing
      radiation, elapsed time from radiation exposure to malignant progression, and
      different histological characteristics or growth rate of the regrowing tumor
      comparing with those originally treated. Three presented cases fulfilled these
      diagnostic criteria; however, it seems that progression of the tumors
      (schwannoma, meningioma, chordoma) resulted from the natural course of the
      disease, rather than represented side effects of gamma knife radiosurgery.
      Evaluation of the proliferative potential of the benign neoplasm before
      radiosurgical treatment either directly, if tumor sampling is available, or
      indirectly, by calculation of the tumor growth rate and/or analysis of the data
      of the metabolic imaging (PET, MRS) is important for identification of
      "aggressive" subtypes, precise prediction of prognosis, and confirmation of the
      radiation-induced malignant transformation in cases of tumor regrowth.

PMID- 16432784
TI  - Fully endoscopic endonasal vs. transseptal transsphenoidal pituitary surgery.
AB  - A long-term retrospective study of 300 patients who underwent fully endoscopic
      endonasal pituitary adenoma resection between November 1998 and October 2004. The
      patients' records as well as the data obtained from postoperative follow-up
      visits was used to determine outcomes. Additionally, the data were then compared
      to mean values calculated from several transseptal-transsphenoidal reports. From
      a total of 300 pituitary adenomas, 139 (46 %) were hormonally active, while 161
      (54 %) were non-functioning. Mean follow-up period was 38.2 months. The average
      length of hospital stay (LOS) was 1.4 days. All patients had postoperative
      magnetic resonance imaging (MRI) studies to assess residual or recurrent disease;
      all patients with hormonally active tumors had additional postoperative hormonal
      studies. Remission, being defined as no hormonal or radiological evidence of
      recurrence within the time-frame of the follow-up, was demonstrated in 127/134
      (95 %) of enclosed and 144/166 (87 %) of invasive adenomas. A comparison of fully
      endoscopic endonasal vs. transseptal-transsphenoidal remission results revealed
      an improved outcome using the fully endoscopic endonasal technique: ACTH (86 %
      vs. 81 %), PRL (89 % vs. 66 %) and GH (85 % vs. 77 %). The remission rate for non
      functioning adenomas was 149/161 (93 %). Additionally, we noted a marked
      reduction in complications related to the endoscopic procedure. Our results
      conclude that the fully endoscopic endonasal technique is a safe and effective
      method for removal of pituitary adenomas providing more complete tumor removal
      and reducing complications.

PMID- 16432783
TI  - Laparoscopic anterior lumbar interbody fusion: a review of outcome studies.
AB  - Laparoscopic anterior lumbar interbody fusion (LALIF) was first reported in 1995.
      It was expected to reduce the morbidity of an open ALIF, while maintaining its
      advantages. About a decade after its debut, the feasibility and short-term
      efficacy of the LALIF has been recognized. Currently, other minimally-invasive
      surgical options have been made available for the treatment of lumbar
      degenerative disc disease, and thus the role of LALIF has not been established in
      view of these other methods. The authors aim to clarify this, by conducting a
      review of the literature particularly on the outcome studies of LALIF. Several
      comparative studies showed that at the L5-S1 disc level, there was no marked
      difference between LALIF and the open or mini-open ALIF in terms of short-term
      efficacy, i. e., operative time, blood loss, and length of hospital stay. With
      regard to the complication rate, however, there was a higher incidence of
      retrograde ejaculation in LALIF. At the L4-L5 and L4-L5/L5-S1 disc levels, the
      complication rate and conversion rate to open surgery was high in LALIF, and many
      authors were not impressed with the LALIF at these levels. Several case series
      showed that the LALIF yielded excellent perioperative outcomes in the hands of
      experienced endoscopic spine surgeons at both the L5-S1 and L4-L5 disc levels. No
      conclusion regarding either the superiority or inferiority of LALIF to the open
      or mini-open ALIF can be drawn, because of the lack of data with a high-level of
      evidence. It cannot be denied, however, that some spine surgeons are abandoning
      this procedure and switching to the mini-open ALIF. Treatment of lumbar
      degenerative disc disease itself has been changing rapidly, as represented by the
      recent emergence of the lumbar artificial disc, and the future role of LALIF
      remains to be followed closely.

PMID- 16432785
TI  - Analysis of different surgical approaches for the treatment of cerebrospinal
      fluid rhinorrhea.
AB  - The current treatment method for cerebrospinal fluid (CSF) rhinorrhea is surgical
      repair of the fistula. The aim of this study was to analyse different surgical
      approaches used for the treatment of CSF rhinorrhea regarding several
      preoperative and postoperative variables to determine the optimal method in these
      patients. Patients' charts were retrospectively reviewed to get the required
      data. Twenty-six patients who underwent different types of surgical approach for
      the treatment of CSF rhinorrhea were included in the study. Patients who had
      extensive comminuted fractures of the anterior cranial base and additional brain
      injury besides CSF rhinorrhea, mostly as a result of gunshot injuries, underwent
      craniotomy (n = 14). Osteoplastic frontal sinusotomy was used in two patients
      with a dural defect located at the posterior wall of the frontal sinus.
      Uncomplicated CSF fistulas in ten patients, located at the anterior and posterior
      ethmoid roof and in the sphenoid sinus, were closed with an endonasal endoscopic
      approach. Postoperative success rate was higher (97 % for intracranial approach,
      100 % for extracranial external and endonasal endoscopic approach) for all
      techniques. Anosmia was the most frequent permanent complication (n = 5), seen
      after craniotomy. In conclusion, endonasal endoscopic approach can be preferred
      for the closure of uncomplicated CSF fistula, located at the anterior or
      posterior ethmoid roof and in the sphenoid sinus, due to its minimal
      postoperative morbidity. Uncomplicated CSF fistula, located at the posterior wall
      of frontal sinuses can be repaired extradurally with osteoplastic frontal
      sinusotomy. Intracranial approaches should be reserved for more complicated CSF
      rhinorrhea which results from extensive comminuted fractures of the anterior
      cranial base and is accompanied with intracranial complications.

PMID- 16432786
TI  - The effects of venous ischaemia on the subependymal and choroid plexus morphology
      in rat.
AB  - Morphological changes of ependyma, subependyma and choroids plexus regions were
      evaluated after experimental anastomotic venous occlusion in twenty male Sprague
      Dawley rats. In this model, small burr holes were made over the anterior and
      posterior anastomotic veins and after precisely locating these vessels, bipolar
      coagulation and microscissors were used to perform permanent occlusion. Three
      days later, rats were sacrificed by perfusion and fixation and specimens were
      evaluated by histopathological techniques. Morphological changes of ependymal,
      subependymal and choroids plexus cells were evaluated in operated and intact
      hemispheres and revealed cell proliferation in the subventricular zone adjacent
      to the territory of venous occlusion in the operated hemisphere as well as
      midline shift, brain oedema, subcortical petechial haemorrhage, brain infarction
      and hemispheric swelling. In conclusion, following anterior (the vein of
      Throlard) and posterior (the vein of Labbe) anastomotic vein occlusion, cell
      proliferation can be seen in the choroids plexus, ependymal and subependymal
      regions in rats. We conclude that these morphological changes might be part of a
      self-repairing mechanism in the brain.

PMID- 16432787
TI  - Endoscope assisted removal of jugular foramen schwannoma; report of 3 cases.
AB  - Removal of the intraforaminal portion of a jugular foramen schwannoma under
      direct vision requires resection of the adjacent bone. Extensive resection of the
      bone around the jugular foramen, however, involves a potential danger for
      cerebrospinal fluid (CSF) leakage and for damage to the adjacent cranial nerves
      as well as venous outflow. To avoid such bone resection, we applied the endoscope
      during the removal of a jugular foramen schwannoma through the lateral
      suboccipital approach. Three patients with schwannomas in the jugular foramen
      were treated using the lateral suboccipital approach with endoscopic assistance.
      After the intracranial portion was first removed under the microscope, the
      residual tumor in the jugular foramen was subsequently removed under the side
      viewing endoscope. In all cases the tumor was removed successfully without major
      complications. The authors conclude that if the cases are selected properly,
      removal of the schwannoma extending into the jugular foramen is feasible through
      the conventional lateral suboccipital window under endoscopic assistance.

PMID- 16432788
TI  - Clinical application of artificial dura mater to avoid cerebrospinal fluid leaks
      after microvascular decompression surgery.
AB  - OBJECTIVE: Although technological advances combined with many surgical
      innovations have helped to minimize its occurrence, cerebrospinal fluid (CSF)
      leak still remains to be one of the most common postoperative complications
      following microvascular decompression (MVD) surgeries. The objectives of this
      study are 1) to detail our experience with the clinical application of artificial
      dura mater for the avoidance of CSF leaks in a group of 103 patients who
      underwent MVD surgeries and 2) to compare the results of CSF leak and deep wound
      infection between the group with and one without using artificial dura mater.
      METHODS: From July, 2002 to June, 2004 217 consecutive patients who underwent MVD
      surgeries for hemifacial spasm or trigeminal neuralgia in our center were
      enrolled into this study. Among them, 103 patients underwent the application of
      artificial dura mater (Neuro-patch) in the surgical closure procedure to prevent
      postoperative CSF leak. The handling techniques were detailed and the
      postoperative results were evaluated. The follow-up period was at least 6 months.
      RESULTS: No postoperative CSF leak occurred in the group of patients receiving
      artificial dura mater whereas 6 cases of CSF leak (2 otorrhea, 2 rhinorrea and 2
      CSF wound leak) were found in the group not receiving artificial dura mater.
      There was no statistical difference of wound infection rates found between these
      two groups, 1.9 % vs. 2.6 %. CONCLUSIONS: The use of the artificial dura mater in
      the closure procedure of MVD surgery seems to be a safe and effective way to
      prevent CSF leaks. However, further investigations on a larger number of cases
      still need to be done to substantiate its validity.

PMID- 16432789
TI  - Irrigation-suction straw sheath system for a rigid endoscope during endonasal
      endoscopic pituitary surgery.
AB  - OBJECTIVE: One of the most problematic conditions during endonasal endoscopic
      pituitary surgery is blurred endoscopic vision caused by blood or bone dust. To
      address this problem we used a new device, the irrigation-suction straw sheath
      system originally developed for endoscopic sinus surgery in rhinology, for the
      endoscopic pituitary surgery. METHODS: The irrigation-suction straw system (K
      endosheath; Koken Co., Tokyo, Japan) consists of a flattened disposable straw
      catheter which can be attached on a rigid endoscope. When the endoscope is
      inserted into the oblong catheter, two gaps remain on either side of the
      endoscope. Through each of these gaps irrigation and continuous suction are
      performed respectively. RESULTS: Clear vision could be immediately obtained by
      pressing the button to release the irrigation water onto the endoscope's front
      lens. Even targeted irrigation during drilling was possible. Above all,
      continuous suction was useful to clear the operative field of blood, smoke, or
      bone dust, ensuring the safety and uninterrupted progress of the procedure.
      CONCLUSION: This irrigation-suction system has proved to be very useful and easy
      to use for endonasal endoscopic pituitary surgery. Further development of such
      new devices and instruments specialized for endonasal endoscopic pituitary
      surgery will promote the increased use of this minimally invasive technique in
      neurosurgery.

PMID- 16432790
TI  - [Legislative policy and management in relation to long term care in Taiwan].
AB  - Because of the ageing of Taiwan society, long-term care needs increase on a daily
      basis. But no shift system has been introduced for long-term care, with the
      result that when there is an inappropriate balance of deployment of resources,
      acute hospital resources are being given over to long-term care patients, and a
      heavy burden is being placed upon long-term care patients and their families. In
      addition, there are developmental differences within the current system, in which
      many different management methods are adopted. For this reason, this article
      describes the difficulties that long-term care faces in Taiwan, and makes
      suggestions in that regard. In an ageing society, integration of policy,
      legislation and services, the provision of welfare to the elderly, are
      responsibilities of the whole of society--the elderly themselves, their families,
      civil society, and government. We sincerely hope that legislation on long-term
      care can now be passed quickly, so that a truly flawless long-term care system
      can be introduced.

PMID- 16432791
TI  - [Perspectives in evaluating quality of home care].
AB  - When evaluating home care quality, one must include the patients, the carer and
      the family as a whole. The goal of service provision should be holistic care.
      This paper raises new perspectives, using the "structure," "process," and
      "outcome," of Donabedian evaluation theory as a vertical axis, and the key
      elements of quality--the subjective and the objective--as the horizontal axis.
      Evaluation should also emphasize a democratic approach and appraisal of the
      process of delivery of services.

PMID- 16432792
TI  - [The self-determination and family empowerment of nursing home residents].
AB  - Long-term care for the elderly, disabled and handicapped is changing, with the
      trend shifting away from the prior emphasis on professional qualifications and
      cost management and toward allowing individuals increased authority to influence
      care policies and determine services provided. Within this trend, increased
      participation by family members, expanded care recipient rights, and family
      empowerment are driving the development of a new cooperative relationship between
      professional health care providers, care recipients and their families.

PMID- 16432793
TI  - [Application of empowering education in long-term care facilities: the experience
      with foreign nurse aides].
AB  - The concept of empowerment, widely accepted and utilized in many health-related
      disciplines, connotes a process of gaining control over one's life and
      influencing the organizational and social structures in which one lives. This
      article demonstrates an example of how empowering education can be applied on
      foreign nursing aides working in long-term care facilities and how differing
      empowering strategies, processes and effects can be adopted to address differing
      situations and ethnic backgrounds. How high priority issues of concern for
      foreign nurses are handled impacts upon their ability to perform their jobs well.
      Empowering strategies can help deal with such issues more effectively and, as a
      result, reduce work stress and improve on-the-job performance. During the
      preparation stage, the empowerment process focuses on building a trusting partner
      relationship. During the work stage, the process focuses on inspiring foreign
      nurses' self-awareness, encouraging their perceiving the barriers and needs at
      work, and, most importantly, encouraging nurses to think critically and
      positively and to provide feedback. The effects of empowering education include
      enhanced problem solving abilities, rising nurse self-confidence in his/her
      caretaking abilities, enhanced self-esteem, and improved adaptation to the work
      environment. This paper provides empirical experiences with regard to the
      application of empowering education in clinical settings as well as process and
      management strategies related to foreign nursing aides employed in long-term care
      facilities.

PMID- 16432794
TI  - [A project to raise the participation rate in education groups by psychiatric
      patient family members].
AB  - The objective of this project was to increase the rate of participation in
      relevant educational programs of immediate relatives of individuals currently
      undergoing psychiatric treatment. According to statistics, the average
      participation rate in such educational programs averages only 23.4%; a ratio
      considered unacceptably low. After analysis, major problems identified included:
      (1) relatives were not informed in advance of meeting schedules; (2) there was no
      standard manner by which hospitals communicated with relatives; (3) interaction
      between patients and their families was, in general, poor; (4) program staff were
      unable to ensure that relatives knew correct meeting times; and (5) relatives
      generally lacked interest in health education topics. A special project group was
      organized and charged to improve the rate of participation of psychiatric patient
      relatives in health education groups. Three proposals made by this group
      included: (1) create an annual patient relative attendance planning schedule; (2)
      implement a patient "life passport" for use as a standardized tool in day
      hospital care; and (3) arrange time after education activities for patient-parent
      interaction. After measures were implemented, patient relative participation in
      education programs rose to 64.8% from 23.4%. Results demonstrate method
      feasibility and validity. As the proposed method does not require nurses to send
      out notifications or conduct follow-ups over the phone, it indirectly cuts down
      costs and manpower and improves patient-family relations, ultimately raising the
      quality of nursing care.

PMID- 16432795
TI  - [The relationship between in-hospital breastfeeding rates and hospital type].
AB  - The objective of this study was to examine the impact of hospital environment on
      breastfeeding rates during maternal hospitalization. This study applied a
      descriptive correlational design. The study population consisted of mothers who
      had given birth to infants in the Taiwan area between June and October 2003. A
      proportional probability sampling method was used. Samples were drawn based on
      the mother's residence in one of six regions: eastern, central, southern, and
      northern Taiwan, Taipei City, or Kaohsiung City. The rates of exclusive and mixed
      breastfeeding during hospitalization were found to be 17.9% and 47%,
      respectively. Bi-variable analysis showed that higher-level hospitals, certified
      baby-friendly hospitals, teaching hospitals, hospitals with higher annual birth
      numbers, and public hospitals all had higher rates of breastfeeding. Logistic
      regression results demonstrated the positive influence of institutional factors
      associated with breastfeeding (any and exclusive breatfeeding) when social
      demographic and perinatal variables were controlled in the model. Baby-friendly
      and higher-level hospitals had the highest breastfeeding rates. Women who
      delivered at baby-friendly and teaching hospitals had higher exclusive
      breastfeeding rates. The results of this research can serve as a reference to the
      government and medical institutions in relation to efforts to promote
      breastfeeding.

PMID- 16432796
TI  - [Ethnography and nursing research].
AB  - Ethnography, a qualitative research method developed within the field of
      anthropology, has been increasingly applied to a variety of fields, including
      sociology, education, and nursing. Ethnography works to understand the behavior
      and views of a particular cultural group from that group's own perspective.
      Traditionally, ethnography has been differentiated into classic ethnography,
      systematic ethnography, interpretive ethnography, and critical ethnography. A
      recently developed focused ethnography studies specific issues within a single
      culture or social situation among a limited number of people within a specific
      period of time. Focused ethnography is particularly relevant to the field of
      health sciences and holds significant potential to contribute to nursing
      knowledge and to help improve nursing practice. A search of Medline, CINAHL,
      Eric, PsycINFO, and the Index to Chinese Periodical Literature database found
      that ethnography has seldom been applied or discussed in the nursing literature
      in Taiwan. Therefore, the aim of this article is focused on introducing
      ethnography and understanding the applications of ethnography in nursing
      research. Relevant nursing literature published between 2000 and 2005 is
      summarized and the authors hope that this paper will give Taiwanese nursing
      professionals a better appreciation of this methodology and encourage its wider
      application in nursing research.

PMID- 16432797
TI  - [The introduction and inspiration to a sexual assault nurse examiner in forensic
      nursing].
AB  - A number of regulations concerning women and children have been introduced
      recently in Taiwan, and those regulations have improved the safety for women and
      children. But there remain problems as far as evidence gathering for medical and
      forensic purposes is concerned, giving rise to continuing difficulties in
      enforcing the regulations. Sexual assault nurse examiners (SANEs) perform one of
      several recognized forensic nursing roles. The position of SANE was developed to
      improve medical care for persons who have been sexually assaulted. The SANE
      education program combines the roles of nursing/medicine, law enforcement,
      prosecution, and advocacy to provide services involving both compassion and
      comprehensive medical-legal evaluation by a specially trained professional who
      has the experience to anticipate their needs during this time of crisis. This
      paper introduces SANEs in forensic nursing, discusses the way forensic nursing is
      conducted and introduces Taiwan's SANE training program for sexual assault
      victims.

PMID- 16432798
TI  - [Nurses' roles and functions in early intervention].
AB  - Early intervention is a group cooperative medical service. This article aims to
      illustrate the knowledge required by nurses who intend to practice in areas of
      early intervention. The contents consist of definitions, laws, and current
      practices in early intervention in Taiwan and the United States. In addition, the
      roles and responsibilities of nurses in transdisciplinary early intervention
      teams will also be introduced. This article will serve as an introduction for
      nurses practicing early intervention. We would also encourage the addition of the
      knowledge that it introduces to continuing education programs to enhance nurses'
      abilities in the screening and management of cases.

PMID- 16432799
TI  - [Music therapy and child care].
AB  - Music therapy was shown many years ago to have positive effects in various age
      groups of patients in the Western world. Music can produce physiological and
      psychological effects, including changes in the vital signs, reductions in
      anxiety, improvements in the immune system, decreases in cortisol levels, the
      reduction of stress and the promotion of well-being. Music therapy is an
      inexpensive and effective intervention for nurses to apply to patients. The
      application of such therapy to children, however, is different from that to
      adults due to their limited cognitive and language development. In Taiwan,
      nurses' knowledge of music therapy is limited, and it is rarely used in child
      care. This article introduces music therapy and its effects in child care, such
      as in premature infants, children in emergency care, handicapped children, and
      children receiving surgery. Music therapy is often used as an assisted
      intervention for patient care in clinical settings. Health care professionals can
      perform some of the music therapy activities for patients appropriately even if
      they have not been trained in music. This article aims to improve nurses'
      knowledge of music therapy and to provide a useful reference for those involved
      in child care.

PMID- 16432800
TI  - [The positioning of nursing research in the academic studies: the origin and
      development of qualitative and quantitative studies].
AB  - The purpose of this study is to discuss the historical context of qualitative and
      quantitative research so as to explain the principle of qualitative study and
      examine the positioning of nursing research within academic study as a whole.
      This paper guides the readers towards the historical context from empirical
      science, discusses the influences of qualitative and quantitative research on
      nursing research, then investigates the nature of research paradigms, examines
      the positioning of nursing research, which includes the characteristics of fields
      such as natural science, humanity and social studies, and science, and lastly,
      presents the research standard proposed by Yardley in 2000. The research
      paradigms include Positivism, Postpositivism, Criticism, and Constructivism,
      which can be compared with Ontology, Epistemology, and Methodology. The nature of
      the paradigm is to determine the assumption of the paradigm on the basis of
      Ontology, Epistemology, and Methodology. The paradigm determines how the
      researcher views the world and decides on what to answer, how to research, and
      how to answer. The difference in academic environment is reflected in the long
      term dialogue between qualitative and quantitative studies, as well as the
      standard for criticism. This paper introduces the method of evaluation of the
      quality of qualitative study proposed by Yardley in 2002, namely the sensitivity
      of the context, the promise and conscientiousness, transparency and consistency,
      influence and significance. The paper is intended to provide a guideline for
      readers in evaluating the quality of qualitative study.

PMID- 16432801
TI  - [An experience of taking care of an adolescent spinal surgery patient suffering
      from scoliosis].
AB  - This case report describes the experience of taking care of an adolescent
      (nineteen year-old) girl, who needed spinal surgical treatment because of
      scoliosis. The author assessed the patient's condition by observation, interview,
      and the Gordon 11-item functional health pattern assessment guide. Because she
      had had no previous surgical experience, and faced changes in her bodily
      appearance, the adolescent had physical and psychological problems, such as acute
      pain, self-care deficit, anxiety, and body image disturbance. Besides applying
      professional knowledge and technical ability, to alleviate the discomfort caused
      by the young lady's surgery, the author used caring, listening and empathy to
      encourage and support her in learning self-care, to accept her change in body
      image, and to overcome the impact of the disease. Through this nursing process,
      the author came to understand that nurses must concern themselves with both
      physical problems and mental needs in order to provide holistic health care.

PMID- 16432802
TI  - [An experience of nursing a client with myasthenia gravis].
AB  - Myasthenia gravis is an autoimmune disease. It causes the formation of certain
      antibodies that attack acetylcholine receptors. The consequent reduction in the
      number of acetylcholine receptors causes impairment in the transduction of neural
      pulses (Cross, 1999). Clients usually present with ineffective breathing
      patterns, high risk of aspiration, and activity intolerance. Myasthenia gravis
      poses a threat not only to the lives of clients, but also of psychological and
      social impairment. The author describes the nursing evaluation undertaken during
      the process of caring for a client with myasthenia gravis, and, using Gorden's
      functional health assessment guide, summarizes six nursing problems, including
      high risk of aspiration, activity intolerance, knowledge deficit, powerlessness,
      ineffective breathing pattern and high risk of injury. Nursing intervention using
      multiple measures improved this client's symptoms of adjustment and understanding
      of the disease, while also raising the caring ability and quality of life of both
      client and family.

PMID- 16432803
TI  - Structural characterization of flavonol 3,7-di-O-glycosides and determination of
      the glycosylation position by using negative ion electrospray ionization tandem
      mass spectrometry.
AB  - Flavonol 3,7-di-O-glycosides were investigated by negative ion electrospray
      ionization tandem mass spectrometry using a quadrupole linear ion trap (LIT) mass
      spectrometer. The results indicate that the fragmentation behavior of flavonol
      3,7-di-O-glycosides is substantially different from that of their isomeric mono-O
      diglycosides. In order to characterize a flavonoid as a flavonol 3,7-di-O
      glycoside, both [Y3(0) - H]-* and [Y(0) - 2H]- ions should be present in [M - H]-
      product ion spectrum. The MS(3) product ion spectra of Y3(0)-, [Y3(0) - H]-* and
      Y7(0)- ions generated from the [M - H]- ion provide sufficient structural
      information for the determination of glycosylation position. Furthermore, the
      glycosylation positions are determined by comparing the relative abundances of
      Y3(0)- and Y7(0)- ions and their specific fragmentation patterns with those of
      flavonol mono-O-glycosides. In addition, a [Y3(0) - H]-* ion formed by the
      homolytic cleavage of 3-O glycosidic bond with high abundance points to 3-O
      glycosylation, while a [Y(0) - 2H]- ion formed by the elimination of the two
      sugar residues is consistent with glycosylation at both the 3-O and 7-O
      positions. Investigation of negative ion ESI-MS(2) and MS(3) spectra of flavonol
      O-glycosides allows their rapid characterization as flavonol 3,7-di-O-glycoside
      and their differentiation from isomeric mono-O-diglycosides, and also enables
      their direct analysis in crude plant extracts.

PMID- 16432804
TI  - On the lottery equivalents method: a response to Spencer et al.

PMID- 16432805
TI  - Synthesis of tetrazole analogs of gamma- and delta-amino acids.
AB  - N-benzyloxycarbonyl-protected alpha- or beta-amino alcohols, easily prepared from
      alpha- and beta-amino acids, were converted into aldehydes and directly reacted
      with (triphenyl phosphoranylidene) acetonitrile, leading to unsaturated nitriles.
      Treatment of nitriles with NaN(3) and ZnBr(2) produced unsaturated gamma- and
      delta-amino tetrazoles, which were deprotected and converted to the corresponding
      saturated compounds by catalytic hydrogenation. For the case of delta-amino
      tetrazole, the methylation of the acidic moiety occurred after treatment with
      CH(2)N(2), leading to the N(1)- and N(2)-methylated constitutional isomers, which
      were separated by column chromatography and hydrogenated.

PMID- 16432807
TI  - Deduction of functional peptide motifs in scorpion toxins.
AB  - Scorpion toxins are important physiological probes for characterizing ion
      channels. Molecular databases have limited functional annotation of scorpion
      toxins. Their function can be inferred by searching for conserved motifs in
      sequence signature databases that are derived statistically but are not
      necessarily biologically relevant. Mutation studies provide biological
      information on residues and positions important for structure-function
      relationship but are not normally used for extraction of binding motifs. 3D
      structure analyses also aid in the extraction of peptide motifs in which non
      contiguous residues are clustered spatially. Here we present new, functionally
      relevant peptide motifs for ion channels, derived from the analyses of scorpion
      toxin native and mutant peptides.

PMID- 16432806
TI  - Design of novel bicyclic analogues derived from a potent oxytocin antagonist.
AB  - Eleven new analogues were synthesized by modification of the potent oxytocin
      antagonist (OTA) [(S)Pmp(1), D-Trp(2), Pen(6), Arg(8)]-Oxytocin, or PA (parent
      antagonist), in which (S)Pmp = beta,beta-(3-thiapentamethylene)-beta-mercapto
      propionic acid. By internal acylation of Lys, Orn, L-1,4-diaminobutyric acid
      (Dab), L-1,3-diaminopropionic acid (Dap) at position 4 with the C-terminal Gly of
      the peptide tail, we prepared cyclo-(4-9)-[Lys(4), Gly(9)]-PA (pA(2) = 8.77 +/-
      0.27), 1, and cyclo-(4-9)-[Orn(4), Gly(9)]-PA (pA(2) = 8.81 +/- 0.25), 3, which
      are equipotent with PA (pA(2) = 8.68 +/- 0.18) in the rat uterotonic assay and
      cyclo-(4-9)-[Dab(4), Gly(9)]-PA, 4, cyclo-(4-9)-[Dap(4), Gly(9)]-PA, 5, and cyclo
      (4-9)-[Pmp(1), Lys(4), Gly(9)]-PA, 2, which were weaker OTAs. Neither 1 nor 3 had
      activity as agonists or antagonists in the antidiuretic assay. In the pressor
      assay, both analogues 1 and 3, with pA(2) = 7.05 +/- 0.10 and pA(2) = 6.77 +/-
      0.12, respectively, are somewhat weaker antagonists than PA (pA(2) = 7.47 +/-
      0.35) showing significant gain in specificity. The [desamido(9)] PA
      ethylenediamine monoamide, 6, and the dimer ([desamido(9)]-PA)(2) ethylenediamine
      diamide, 7, had lower potency in the uterotonic assay than PA. Additionally, we
      synthesized cyclo-(1-5)-[(HN)Pmp(1), Asp(5)]-PA, 8, inactive in all tests, which
      suggests that the intact Asn(5) side chain may be critical in the interaction of
      the OTAs with the oxytocin (OT) receptor. Similarly, cyclo-(5-9)-[Dap(5), Gly(9)]
      PA, 9, had very low uterotonic potency. Two derivatives of PA truncated from the
      C-terminus were internally cyclized to Lys(4), giving rise to cyclo-(4-8)-desGly
      NH(2)(9)[Lys(4), Arg(8)]-PA, 10 (pA(2) = 8.35 +/- 0.20), which maintains the high
      potency of PA and has no activity in the rat antidiuretic assay, and in the rat
      pressor assay it is about ten times weaker (pA2 = 6.41 +/- 0.15) than PA (pA2 =
      7.47 +/- 0.35), thus showing gains in specificity, and to cyclo-(4-7)-desArg-Gly
      (NH)(2)(8-9)[Lys(4), Pro(7))-PA, 11, which has much weaker potency than PA.
      Synthesis of cyclo-(4-6)-desPro-Arg-Gly-(NH)(2)(7-9)[Lys(4)]-PA failed.

PMID- 16432808
TI  - Combining a polar resin and a pseudo-proline to optimize the solid-phase
      synthesis of a 'difficult sequence'.
AB  - This paper describes the optimization of a synthesis of a difficult sequence
      related to a 12-mer sequence of a Pan DR epitope (PADRE). Elongation was followed
      by on-line monitoring of the N(alpha)-Fmoc removal adapted for the batch
      methodology. Studying the intrinsic factors related to the peptide-resin, such as
      substitution level, resin nature and backbone protecting group, has led to an
      increase in the elongation yield and purity of the crude peptide. Optimal
      elongation was obtained by combining a polar resin such as PEGA and a pseudo
      proline as the backbone protecting group.

PMID- 16432810
TI  - Cost-effectiveness analysis of surgery versus conservative treatment for
      uncomplicated varicose veins in a randomized clinical trial.
AB  - BACKGROUND: Despite being a common procedure, the cost effectiveness of surgery
      for varicose veins has not been established. METHODS: Cost-effectiveness analysis
      was carried out alongside a randomized clinical trial at two vascular units
      within National Health Service (NHS) hospitals. Some 246 patients with
      uncomplicated varicose veins and evidence of saphenofemoral or saphenopopliteal
      reflux were allocated randomly to receive either conservative management or
      surgical treatment. Incremental cost per quality-adjusted life year (QALY) gained
      at 24 months following randomization was calculated. RESULTS: Total NHS costs
      during the 2-year study period were higher for the surgically treated group (733
      UK pounds) than for those who had conservative treatment (345 UK pounds). The
      difference in costs was statistically significant. The mean incremental health
      gain from surgical treatment at 24 months was 0.083 QALYs, leading to a base-case
      estimate of 4682 UK pounds per QALY gained. Assuming an implicit threshold
      maximum willingness-to-pay value of 20 000 UK pounds for a QALY, the probability
      of surgical treatment for varicose veins falling below this threshold value was
      70 per cent. This result was found to be robust to sensitivity analysis.
      CONCLUSION: For patients with uncomplicated varicose veins and evidence of
      saphenofemoral or saphenopopliteal reflux, surgical treatment for varicose veins
      offers a modest health benefit for relatively little additional NHS cost relative
      to conservative treatment.

PMID- 16432811
TI  - Retrieval of abdominal organs for transplantation.
AB  - BACKGROUND: Organ retrieval and donor management are not yet standardized.
      Different transplant centres apply various techniques, such as single or dual
      organ perfusion, dissection in the cold or warm, and single or en bloc organ
      removal. These different approaches may cause inconvenience, especially when more
      than one organ retrieval team is involved. METHODS: Cochrane Library, Medline and
      PubMed were searched for publications on multiorgan donor/donation, retrieval
      technique and procurement. Levels of evidence and grades of recommendation were
      evaluated based on current advice from the Oxford Centre for Evidence-Based
      Medicine. RESULTS: Multiorgan donation itself does not compromise the outcome of
      individual organ transplants. Dissection of abdominal organs for transplantation
      is best performed after cold perfusion. Abdominal organs should be removed
      rapidly, en bloc, and separated during back-table dissection in the cold,
      particularly if pancreas or intestine is included. Perfusion itself should be
      carried out after single cannulation of the aorta with an increased pressure.
      CONCLUSION: Although the literature on organ retrieval is extensive, the level of
      evidence provided is mainly low. Nevertheless, optimized donor treatment and
      organ retrieval should increase the number and quality of cadaveric donor organs
      and improve graft function and survival.

PMID- 16432812
TI  - Bile duct injury in the era of laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy is the standard of care for symptomatic
      cholelithiasis, but it is associated with a higher incidence of bile duct injury
      than the open approach. METHODS: A review was performed of the English language
      literature on the management of bile duct injury listed on Medline databases.
      RESULTS AND CONCLUSION: There is consensus that careful dissection and correct
      interpretation of the anatomy avoids the complication of bile duct injury during
      cholecystectomy. Routine intraoperative cholangiography is associated with a
      lower incidence and early recognition of bile duct injury. Early detection and
      repair is associated with an improved outcome, and the minimum standard of care
      after the recognition of a bile duct injury is immediate referral to a surgeon
      experienced in bile duct injury repair. Surgery provides the mainstay of
      treatment, with proximal hepaticojejunostomy Roux en Y being the operation of
      choice; a selective role for endoscopic or radiological treatment exists. The
      outcome after bile duct injury remains poor, especially in relation to the
      initial expectation of the cholecystectomy. Patients are often committed to a
      decade of follow-up.

PMID- 16432813
TI  - Long-term results of abdominal salvage surgery following restorative
      proctocolectomy.
AB  - BACKGROUND: This study evaluated outcomes of patients who underwent abdominal
      salvage ileal pouch redo surgery and identified factors associated with pouch
      failure following restorative proctocolectomy. METHODS: Data on patients who
      underwent abdominal salvage surgery in a tertiary referral centre between 1985
      and 2003 were collected. Outcomes studied included failure of salvage and bowel
      function of patients with an intact intestine. RESULTS: One hundred and twelve
      patients underwent 117 pouch salvage procedures for ulcerative colitis (86),
      indeterminate colitis/ulcerative colitis (eight), indeterminate colitis/Crohn's
      disease (three), familial adenomatous polyposis (ten) and other conditions
      (five). The most common indications for pouch salvage were intra-abdominal sepsis
      (45 patients), anastomotic stricture (13) and retained rectal stump (35). Median
      follow-up was 46 (range 1-147) months. Twenty-four patients (21.4 per cent)
      experienced pouch failure, the incidence of which increased with time. The pouch
      failed in all patients with Crohn's disease. Successful salvage at 5 years was
      significantly associated with non-septic (85 per cent) rather than septic (61 per
      cent) indications (P = 0.016). Frequency of night-time defaecation and faecal
      urgency improved after salvage surgery (P = 0.036 and P = 0.016 respectively at 5
      year follow-up; n = 32). CONCLUSION: Abdominal salvage surgery was associated
      with a failure rate of 21.4 per cent. A successful outcome was less likely when
      the procedure was carried out for septic compared with non-septic indications.
      The rate of pouch failure increased with length of follow-up.

PMID- 16432814
TI  - Mid-term results of endovascular repair of abdominal aortic aneurysm (Br J Surg
      2005; 92: 925-927); Cost-effectiveness of endovascular abdominal aortic aneurysm
      repair (Br J Surg 2005; 92: 960-967).

PMID- 16432816
TI  - Prospective nationwide analysis of laparoscopic versus Lichtenstein repair of
      inguinal hernia (Br J Surg 2005; 92: 1277-1281).

PMID- 16432818
TI  - Randomized clinical trial of vertical or transverse laparotomy for abdominal
      aortic aneurysm repair (Br J Surg 2005; 92: 1208-1211).

PMID- 16432819
TI  - Caution with sentinel node biopsy in cutaneous melanoma.

PMID- 16432820
TI  - Randomized clinical trial comparing multiple stab incision phlebectomy and
      transilluminated powered phlebectomy for varicose veins.
AB  - BACKGROUND: The aim was to compare early postoperative subjective outcome
      measures in a randomized trial of multiple stab incision phlebectomy (MSIP) and
      transilluminated powered phlebectomy (TIPP) for the treatment of varicose veins.
      METHODS: Patients having surgery for varicose veins were randomized to receive
      either MSIP or TIPP for local avulsion of varicose veins. Operating time, number
      of incisions and postoperative outcome were analysed in both groups. Quality of
      life (QoL) was analysed before and 1 and 6 weeks after surgery using domain
      specific (Burford pain scale), disease-specific (Aberdeen Varicose Vein
      Questionnaire) and generic (Short Form 36 and EuroQol 5D) instruments. RESULTS:
      Sixty-six patients consented to participate in the trial but four withdrew before
      surgery, so 33 patients underwent MSIP and 29 patients had TIPP. All patients had
      symptomatic or complicated varicose veins. There was no significant difference
      between groups in the total duration of surgery or the time taken for the
      avulsions. The number of incisions was significantly lower with TIPP. However,
      skin bruising at 1 and 6 weeks, and Burford pain score at 6 weeks were
      significantly higher in the TIPP group (P < 0.01 for bruising and P = 0.019 for
      pain). TIPP also had a greater adverse impact on generic QoL, resulting in a more
      prolonged recovery. CONCLUSION: TIPP had the advantage of fewer surgical
      incisions, but was associated with more extensive bruising, prolonged pain and
      reduced early postoperative QoL.

PMID- 16432821
TI  - Bull testicular haploid germ cells express a messenger encoding for a truncated
      form of the protein tyrosine kinase HCK.
AB  - Protein tyrosine phosphorylation is a process that has been studied worldwide
      during sperm capacitation and acrosomal exocytosis events. Although few
      capacitation-induced phosphotyrosine-containing proteins have been identified,
      little is known about the tyrosine kinases directly involved in this post
      translational modification. Different studies from our and other groups using
      tyrosine kinase inhibitors suggest the involvement of members of the family of
      src-related tyrosine kinases in the sperm capacitation associated increase in
      protein tyrosine phosphorylation. Using a molecular biology approach, we report
      for the first time messengers encoding for members from the src-related tyrosine
      kinase family in bovine spermatogenic cells. Degenerated primers were designed
      within a highly homologous region specific to the family of src tyrosine kinases,
      and RNAs coding for c-src, c-yes, lyn, lck, and hck were identified in bull
      testis and haploid germ cells by RT-PCR. We also report the presence of a
      messenger in haploid bull germ cells that could encode for a truncated isoform of
      the hck tyrosine kinase. This messenger was detected by screening of a haploid
      germ cells cDNA library using the RT-PCR product homologous to hck as a probe.
      The presence of this transcript in haploid germ cell RNA preparations was
      validated by RT-PCR, 3'RACE, 5'RACE as well as Northern blot. Such a truncated
      protein could function as an adaptor protein or as a competitive inhibitor in
      spermiogenesis or mature sperm functions.

PMID- 16432822
TI  - Tyrosine protein kinases and spermatogenesis: truncation matters.
AB  - Protein phosphorylation on serine/threonine or tyrosine residues represents a
      significant regulatory mechanism in signal transduction during spermatogenesis,
      oogenesis, and fertilization. There are several families of tyrosine protein
      kinases operating during spermatogenesis: the Src family of tyrosine protein
      kinases; the Fujinami poultry sarcoma/feline sarcoma (Fps/Fes) and Fes-related
      protein (Fer) subfamily of non-receptor proteins; and c-kit, the transmembrane
      tyrosine kinase receptor that belongs to the family of the PDGF receptor. A
      remarkable characteristic is the coexistence of full-length and truncated
      tyrosine kinases in testis. Most of the truncated forms are present during
      spermiogenesis. Examples include the truncated forms of Src tyrosine kinase
      hematopoietic cell kinase (Hck), FerT, and tr-kit. A feature of FerT and tr-kit
      is the kinase domain that ensures the functional properties of the truncated
      protein. FerT, a regulator of actin assembly/disassembly mediated by cortactin
      phosphorylation, is present in the acroplaxome, a cytoskeletal plate containing
      an F-actin network and linking the acrosome to the spermatid nuclear envelope.
      This finding suggests that Fer kinase represents one of the tyrosine protein
      kinases that may contribute to spermatid head shaping. The c-kit ligand, stem
      cell factor (SCF), which induces c-kit dimerization and autophosphorylation,
      exists as both membrane-associated and soluble. Although tyrosine protein kinases
      are prominent in spermatogenesis, a remarkable observation is the paucity of
      phenotypic alterations in spermatogenic cells in male mice targeted with Fer
      kinase-inactivating mutation. It is possible that the redundant functions of the
      tyrosine protein kinase pool present during spermatogenesis may explain the
      limited phenotypes of single mutant mice. The production of compound and viable
      mutant mice, lacking the expression of two or more tyrosine kinases, may shed
      light on this intriguing issue.

PMID- 16432823
TI  - Treatment of loculated lactational breast abscess with a vacuum biopsy system (Br
      J Surg 2005; 92: 1225-1226).

PMID- 16432825
TI  - Randomized clinical trial comparing surgery with conservative treatment for
      uncomplicated varicose veins.
AB  - BACKGROUND: Surgical treatment of medically uncomplicated varicose veins is
      common, but its clinical effectiveness remains uncertain. METHODS: A randomized
      clinical trial was carried out at two large acute National Health Service
      hospitals in different parts of the UK (Sheffield and Exeter). Some 246 patients
      were recruited from 536 consecutive referrals to vascular outpatient clinics with
      uncomplicated varicose veins suitable for surgical treatment. Conservative
      management, consisting of lifestyle advice, was compared with surgical treatment
      (flush ligation of sites of reflux, stripping of the long saphenous vein and
      multiple phlebectomies, as appropriate). Changes in health status were measured
      using the Short Form (SF) 6D and EuroQol (EQ) 5D, quality of life instruments
      based on SF-36 and EuroQol, complications of treatment, symptomatic measures,
      anatomical extent of varicose veins and patient satisfaction. RESULTS: In the
      first 2 years after treatment there was a significant quality of life benefit for
      surgery of 0.083 (95 per cent confidence interval (c.i.) 0.005 to 0.16) quality
      adjusted life years (QALYs) based on the SF-6D score and 0.13 (95 per cent c.i.
      0.016 to 0.25) based on the EQ-5D score. Significant benefits were also seen in
      symptomatic and anatomical measures. CONCLUSION: Surgical treatment provides
      symptomatic relief and significant improvements in quality of life in patients
      referred to secondary care with uncomplicated varicose veins.

PMID- 16432826
TI  - Varicose veins.

PMID- 16432827
TI  - Value of fluorodeoxyglucose positron emission tomography in women with breast
      cancer (Br J Surg 2005; 92: 1363-1367).

PMID- 16432830
TI  - Unexpected long-term survival after low-dose palliative radiotherapy for non
      small cell lung cancer.
AB  - BACKGROUND: Many experienced oncologists have encountered patients with proven
      non-small cell lung cancer (NCLC) who received modest doses of palliative
      radiotherapy (RT) and who unexpectedly survived for > 5 years; some were
      apparently cured. We used a very large prospective database to estimate the
      frequency of this phenomenon and to look for correlative prognostic factors.
      METHODS: Patients with histologically or cytologically proven NSCLC, treated with
      palliative RT to a dose of < or = 36 Gy, were identified from a prospective
      database containing details of 3035 new patients registered from 1984-1990.
      RESULTS: An estimated 1.1% (95% confidence interval, 0.7-1.6%) of 2337 palliative
      RT patients survived for 5 or more years after commencement of RT, including 18
      patients who survived progression-free for 5 years. Estimated median survival was
      4.6 months. Five-year survivors had significantly better Eastern Cooperative
      Oncology Group performance status at presentation than non-5-year survivors (P =
      0.024) and were less likely to have distant metastases (P = 0.020). RT dose did
      not appear to be a significant prognostic factor. Patients who survived 5 years
      without progression had an estimated 78% probability of remaining free from
      progression in the next 5 years. CONCLUSIONS: Approximately 1% of patients with
      proven NSCLC survived for > 5 years after palliative RT, and many of these
      patients appeared to have been cured by a treatment usually considered to be
      without curative potential. Because of the potential for long-term survival,
      doses to late-reacting normal tissues should be kept within tolerance when
      prescribing palliative RT in NSCLC.

PMID- 16432831
TI  - Clinicopathological characteristics of colorectal cancers with loss of imprinting
      of insulin-like growth factor 2.
AB  - Loss of imprinting (LOI), the biallelic expression of an imprinting gene, of
      insulin-like growth factor 2 (IGF2) has been reported to be associated with
      colorectal carcinogenesis because of its high prevalence in normal colorectal
      mucosa as well as cancerous tissue in patients with colorectal cancer. However,
      the characteristics of colorectal cancer associated with IGF2 LOI have not been
      clearly demonstrated. In this study, we investigated the IGF2 LOI status of tumor
      and normal mucosa in 255 consecutive patients with colorectal cancer. Of these,
      95 were informative for IGF2 LOI, by direct sequencing of mRNA of IGF2. Regarding
      the LOI status in each patient, the prevalence of LOI in nontumorus normal mucosa
      was significantly higher in cases with LOI-positive cancer than in those with LOI
      negative cancer (p < 0.001). Concerning the clinicopathological characteristics
      of LOI-positive cancer, the prevalence of poorly differentiated or mucinous
      carcinoma (p = 0.016) and of right-sided locations (p = 0.009) were significantly
      higher than those of LOI-negative cancer. Contrary to past reports that revealed
      a significant correlation between microsatellite instability (MSI) and IGF2 LOI
      in a relatively small series of noncohort patients, our study did not find a
      statistically significant difference in LOI-positive rate between MSI-positive
      and -negative cases. Our results suggested the presence of a particular type of
      colorectal cancer associated with the proximal colon and poor differentiation,
      but independent of MSI. These results may contribute to clarification of the
      mechanism of colorectal tumorigenesis and to determining an appropriate screening
      strategy for colorectal carcinoma.

PMID- 16432832
TI  - Serological immune response to cancer testis antigens in patients with pancreatic
      cancer.
AB  - Serological screening approaches have allowed for the identification of a large
      number of potentially relevant tumor antigens in cancer patients. Within this
      group, cancer testis antigens represent promising targets for cancer
      immunotherapy, since they are widely expressed in a variety of human cancer
      entities. In pancreatic cancer, however, there are only few data available about
      the expression pattern and serological response to cancer testis antigens and
      other serological-defined tumor antigens. Therefore, we investigated the IgG
      antibody response against 11 cancer testis antigens (SCP-1, GAGE, LAGE-1a,-1b, CT
      7, NY-ESO-1, SSX-1-5) recombinantly expressed on yeast surface (RAYS) in patients
      with pancreatic cancer (n = 96), chronic pancreatitis (n = 18) and healthy donors
      (n = 48). We found in 14% of all patients antibody responses to SCP-1, but not to
      other cancer testis antigens (GAGE, LAGE-1a,-1b, CT-7, NY-ESO-1, SSX-1-5).
      Antibody response correlated with the expression of SCP-1 in the primary tumor of
      the respective patient as shown by RT-PCR, immunohistochemistry and Western blot.
      In contrast, no serological response to cancer testis antigens was observed in
      healthy donors. The humoral immune response against SCP-1 was associated with the
      size of tumor, but not with other clinico-pathological parameters such as
      histology, stage, presence of lymph node metastases, grading, age, gender or
      gemcitabine treatment. In conclusion, antibody response to cancer testis antigen
      SCP-1 is found in a proportion of pancreatic carcinoma patients. These results
      indicate that identification of additional tumor antigens by serological
      screening of tumor cDNA expression libraries by RAYS is a promising goal in
      pancreatic cancer.

PMID- 16432833
TI  - Down regulation of 3p genes, LTF, SLC38A3 and DRR1, upon growth of human
      chromosome 3-mouse fibrosarcoma hybrids in severe combined immunodeficiency mice.
AB  - We have applied a functional test for tumour antagonizing genes based on human
      chromosome 3 (chr3)-mouse fibrosarcoma A9 MCHs that were studied in vitro and
      after growth as tumours in severe combined immunodeficiency (SCID) mice.
      Previously, we reported that 9 out of the 36 SCID-tumours maintained the
      transferred chr3 ("chr3+" tumours), but lost the expression of the known human
      TSG fragile histidine triad gene (FHIT) in contrast to 14 other 3p-genes
      examined. Here we report the results of the duplex RT-PCR analysis of 9 "chr3+"
      tumours and 3 parental MCHs. We have examined the expression of 34 human 3p-genes
      from known cancer-related regions of instability, including 13 genes from CER1
      defined by us previously at 3p21.33-p21.31 and 10 genes from the LUCA region at
      3p21.31. We have found that in addition to FHIT, expression of the LTF gene from
      CER1 at 3p21.33-p21.31 was lost in all 9 tumours analyzed. The transcript of the
      solute carrier family 38 member 3 gene (SLC38A3) gene from LUCA region at 3p21.31
      was not found in 8 and was greatly reduced in 1 out of these 9 tumours.
      Expression of the down-regulated in renal cell carcinoma gene (DRR1) gene at
      3p14.2 was lost in 7 and down regulated in 2 "chr3+" tumours. In the SCID-tumour
      derived cell lines treatment with 5-aza-2'-deoxycytidine restored the mRNA
      expression of LTF, indicating the integrity of DNA sequences. Notably that
      transcription of the LTF and 2 flanking genes, LRRC2 and TMEM7, as well as
      transcription of the SLC38A3 gene, were also impaired in all 5 RCC cell lines
      analyzed. Our data indicate these genes as putative tumour suppressor genes.

PMID- 16432834
TI  - Accumulating evidence on passive and active smoking and breast cancer risk.

PMID- 16432835
TI  - A p21/WAF1 mutation favors the appearance of drug resistance to paclitaxel in
      human noncancerous epithelial mammary cells.
AB  - We investigated the mechanisms responsible for paclitaxel resistance in HME-1
      cells (human mammary epithelial cells immortalized with hTERT). These cells were
      exposed to paclitaxel (10 pM for 7 days) and 20 cellular surviving populations
      (PSP) were obtained. PSP demonstrated high levels of resistance to paclitaxel
      cytotoxicity as compared with HME-1 cells. Activation of mdr-1 gene expression
      was observed in 2 PSP. Protein expression analysis using a C-terminal targeted
      antibody showed that 13 PSP were negative for p21/WAF1 expression after ionizing
      radiation (6 Gy) or doxorubicin (100 nM) treatment. Sequencing of the 3 exons of
      the CDKN1A gene revealed that 13 PSP contained a point mutation in exon 2. This
      mutation consisted in a T insertion at codon 104 leading to a premature STOP
      codon appearance. Mismatch amplification mutation assay and RFLP-PCR confirmed
      the presence of the mutation in 16 PSP. Western blot using an N-terminal targeted
      antibody demonstrated that the C-terminal-truncated p21/WAF1 protein (14 kDa) was
      indeed expressed in the 13 PSP. Our data suggest that p21/WAF1 inactivation may
      confer a strong resistance to paclitaxel in noncancerous breast epithelial cells
      harboring a p21/WAF1 mutant.

PMID- 16432836
TI  - Hypersusceptibility to cisplatin carcinogenicity in metallothionein-I/II double
      knockout mice: production of hepatocellular carcinoma at clinically relevant
      doses.
AB  - Metallothionein (MT) is a high-affinity metal binding protein thought to mitigate
      the toxicity of various metals. Cisplatin is a widely used cancer
      chemotherapeutic that is a rodent carcinogen and may have carcinogenic potential
      in humans. MT seems to reduce cisplatin toxicity by binding the metal compound
      but how MT deficiency might impact the carcinogenic effects of cisplatin is
      unknown. Thus, groups (n = 25) of male MT-I/II double knockout (MT-null) or MT
      wild-type (WT) mice were exposed to a single treatment of cisplatin (5 or 10
      mg/kg, i.p.), or left untreated (control) and observed over the next 104 weeks.
      The doses of cisplatin used equate to only a fraction of the total dose used
      typically in clinical settings. In cisplatin-treated MT-null mice, a dose-related
      increase in hepatocellular carcinoma (HCC) occurred (control, 0%; 5 mg/kg, 17%;
      10 mg/kg, 36%) that was not seen in WT mice. Similarly, liver carcinoma
      multiplicity (HCC/liver) was increased markedly by cisplatin but only in MT-null
      mice, indicating the formation of multiple primaries in MT deficient mice.
      Harderian gland carcinoma incidence was also increased by cisplatin treatment in
      MT-null mice but not WT mice. Our results indicate that MT-null mice are
      hypersusceptible to the hepatocarcinogenic effects of cisplatin, and poor MT
      expression may be a predisposing factor for cisplatin-induced secondary tumors
      after chemotherapy.

PMID- 16432837
TI  - 9-O-acetyl GD3 protects tumor cells from apoptosis.
AB  - The ganglioside GD3 (Neu5Ac alpha8Neu5Ac alpha3Gal beta4GlcCer) is an
      intracellular lipid messenger that induces apoptosis by targeting mitochondria in
      various cell types. GD3 can also promote apoptosis when externally added to
      cells. Previous studies showed that the proapoptotic effects of GD3 can be
      counteracted by 9-O-acetylation. To determine whether 9-O-acetyl GD3 (acGD3) has
      a general antiapoptotic potential, the apoptosis-sensitive Jurkat cell line and
      an apoptosis-sensitive variant of the cell line Molt-4 were preincubated with
      micromolar concentrations of acGD3 and then treated with inducers of apoptosis. A
      reduced apoptotic index and an increased cell viability were observed. On the
      other hand, when the Jurkat cells were treated with GD3 for extended periods of
      time, a population was selected that was resistant to apoptosis induction by N
      acetyl sphingosine as well as by the anti-leukemic drug daunorubicin. Comparative
      analysis of gangliosides revealed the formation of acGD3 in the resistant Jurkat
      cells that was not found in the apoptosis-sensitive cells. Conversely, exposing
      the acGD3 positive and apoptosis-resistant cell line Molt-4 to the O
      deacetylating activity of salicylate resulted in a complete disappearance of
      acGD3 and an enhanced sensitivity to N-acetyl sphingosine-mediated apoptosis.
      Formation of acGD3 might thus represent a new mechanism how tumor cells can
      escape apoptosis.

PMID- 16432838
TI  - Cancer risk among Chernobyl cleanup workers in Estonia and Latvia, 1986-1998.
AB  - Two cohorts of Chernobyl cleanup workers from Estonia (4,786 men) and Latvia
      (5,546 men) were followed from 1986 to 1998 to investigate cancer incidence among
      persons exposed to ionizing radiation from the Chernobyl accident. Each cohort
      was identified from various independent sources and followed using nationwide
      population and mortality registries. Cancers were ascertained by linkage with
      nationwide cancer registries. Overall, 75 incident cancers were identified in the
      Estonian cohort and 80 in the Latvian cohort. The combined-cohort standardized
      incidence ratio (SIR) for all cancers was 1.15 (95% confidence interval (CI) =
      0.98-1.34) and for leukemia, 1.53 (95% CI = 0.62-3.17; n = 7). Statistically
      significant excess cases of thyroid (SIR = 7.06, 95% CI = 2.84-14.55; n = 7) and
      brain cancer (SIR = 2.14, 95% CI = 1.07-3.83; n = 11) were found, mainly based on
      Latvian data. However, there was no evidence of a dose response for any of these
      sites, and the relationship to radiation exposure remains to be established.
      Excess of thyroid cancer cases observed may have been due to screening, the
      leukemia cases included 2 unconfirmed diagnoses, and the excess cases of brain
      tumors may have been a chance finding. There was an indication of increased risk
      associated with early entry to the Chernobyl area and late follow-up, though not
      statistically significant. Further follow-up of Chernobyl cleanup workers is
      warranted to clarify the possible health effects of radiation exposure.

PMID- 16432839
TI  - Prophylaxis of oxidative DNA damage by formamidopyrimidine-DNA glycosylase.
AB  - Lying at the gas-exchange interface, lung epithelia may be at risk of oxidation
      induced mutagenesis. Further, inflammation processes possibly consequent on
      smoking liberate reactive oxygen species that multiply the carcinogenic effects
      of tobacco. DNA repair mechanisms play a major role in counteracting the
      deleterious effects of oxidative DNA damage. Some studies find positive
      associations between lung cancer and variations in the human 8-oxoguanine DNA
      glycosylase (hOGG1) gene that encodes a major DNA glycosylase for oxidized
      lesions with sluggish kinetics properties. The bacterial homologue
      formamidopyrimidine-DNA glycosylase (FPG) is 80-fold faster than hOGG1 in
      repairing mutagenic oxidative lesions. Cell-culture studies have shown that FPG
      can be expressed in mammalian cells, where it accelerates DNA repair and abates
      mutagenicity of a wide range of DNA-damaging agents. Prophylaxis of oxidative DNA
      damage and mutation could be achieved in lung epithelia and other tissues of at
      risk individuals by expression of the FPG protein. Currently available vehicles
      for this peculiar type of gene therapy are briefly surveyed.

PMID- 16432840
TI  - Obtaining smoking histories for population-based studies on multiple primary
      cancers: Connecticut, 2002.
AB  - Because of the absence of data on smoking history for patients in cancer
      registries, large population-based studies have been unable to directly assess
      the role of smoking in the risk of multiple primary cancers. In a random sample
      of 618 adults diagnosed with invasive cancer in 2002 and reported to the
      population-based Connecticut (CT) cancer registry, however, search of hospital
      records identified smoking history (current, former, never- or nonsmoker) for
      83.3%. Number of cigarettes per day was known for 71.3% of 289 current or former
      smokers, while duration of quitting was found for 92.3% of 194 former smokers.
      Smoking status was strongly associated with current heavy alcohol use. Hospital
      records appear to be a promising resource for population-based studies on smoking
      histories in relation to risk of multiple primaries, although completeness of
      information needs to be improved in CT and assessments are needed in other cancer
      registries.

PMID- 16432841
TI  - Alanine aminotransferase level as a predictor of hepatitis C virus-associated
      hepatocellular carcinoma incidence in a community-based population in Japan.
AB  - We evaluated the utility of alanine aminotransferase (ALT) measurements in
      predicting the incidence of hepatocellular carcinoma (HCC) in a cohort of 667
      adults with chronic hepatitis C virus (HCV) infection from a community-based
      population in Japan, between 1994 and 2003. Cox proportional hazards regression
      analysis was used to describe the relationship between prediagnostic levels of
      ALT and the rate of HCC, after adjusting for age and gender; hazard ratios (HRs)
      and 95% confidence intervals (CIs) were obtained. Over an average of 8 years of
      follow-up, 52 HCC cases were identified. A significant association between a 20
      IU/L difference in higher ALT level and subsequent HCC incidence was observed (HR
      = 1.2; 95% CI: 1.1, 1.3). An abnormal ALT level (> or =35 IU/L) increased the HCC
      rate by 4-fold compared to a normal ALT level (HR = 4.1; 95% CI: 2.1, 8.0). Among
      551 subjects with at least 4 repeated measurements of ALT, those with
      persistently abnormal ALT levels (n = 118) had a strong, significantly increased
      HCC rate compared to those with persistently normal ALT levels (n = 296) (HR =
      23.2; 95% CI: 3.0, 178.5). This study demonstrates that elevated ALT levels,
      measured on an average of 8 years before HCC diagnosis, predict an increased rate
      of HCV-associated HCC in a community-based population and that utilizing serial
      measurements to identify persistent ALT abnormality may be useful in determining
      HCC risk.

PMID- 16432842
TI  - Reclassification of oligoastrocytomas by loss of heterozygosity studies.
AB  - Oligoastrocytomas (OAs) are WHO grade II or III tumors composed of a mixture of 2
      neoplastic cell types morphologically resembling the cells in oligodendrogliomas
      and diffuse astrocytomas. Investigations on the genetic profile of OAs may yield
      important information for their classification and help for their clinical
      management. We have studied, in 94 OAs (46 WHO grade II and 48 WHO grade III),
      the patterns of loss of heterozygosity (LOH) of 4 genomic regions: 1p, 19q, 17p
      and 10q. Results were as follows: LOH 1p was present in 46% of the tumors; LOH
      19q in 45%; LOH 17p in 22%; LOH 10q in 16%. LOH 1p and 19q were associated in
      32%, other LOH associations were rare (<3%). Patients had a median follow-up of
      30 months. Patients without LOH on 1p had shorter progression free survival than
      patients with LOH on 1p: 30 vs. 132 months, p < 0.0001. MRI indicated that tumors
      without LOH on 1p were often temporal (p < 0.02), and showed signal inhomogeneity
      on T1 and T2 images (p < 0.02) and contrast enhancement (p < 0.04). Thus, LOH on
      1p identifies two subgroups of OAs. OAs without LOH on 1p behave like WHO grade
      II or III diffuse astrocytomas: they have shorter survival, MRI characteristics
      implying malignancy and genetic alterations associated with tumor progression.
      OAs with LOH on 1p, on the other hand, behave like WHO grade II or III
      oligodendrogliomas with 1p loss: they are associated with longer survival and do
      not have MRI or genetic alterations associated with malignancy. These findings
      suggest that the definition of OAs or mixed gliomas could be reshaped in
      agreement with the genetic information.

PMID- 16432845
TI  - Real-time analysis of enzymatic surface-initiated polymerization using surface
      plasmon resonance (SPR).
AB  - The kinetics of enzymatic surface-initiated polymerization of PHB on gold surface
      has been examined by SPR and the resultant polymer layers characterized by AFM
      and FT-IR spectrometry. The immobilized enzyme catalyzed surface-initiated
      polymerization of 3HB-CoA, resulting in the formation of a polymer brush on the
      surface. The rate of polymer growth from the surface was monitored by SPR in real
      time. Polymer growth as measured by the increase in the resonance angle showed no
      apparent lag phase during the polymerization reaction. SPR analysis also revealed
      that the thickness of the polymer film could be controlled by varying the initial
      enzyme density on the surface. The average thicknesses of the PHB film after
      polymerization reaction were 95, 45 and 15 nm for the surfaces that were treated
      with 0.5, 0.3 and 0.1*10(-6) M of enzyme, respectively. The binding of PHA
      synthase at different concentration to the mixed SAMs and subsequent
      polymerization.

PMID- 16432846
TI  - Inhibition of the MEK/MAPK signal transduction pathway strongly impairs the
      growth of Flt3-ITD cells.

PMID- 16432847
TI  - Sideroblastic anemia after bariatric surgery.

PMID- 16432848
TI  - Effects of oxandrolone, an anabolic steroid, on hemostasis.
AB  - This study evaluated the short-term effects of oxandrolone, an anabolic
      androgenic synthetic steroid, on blood coagulation and the
      hemostatic/fibrinolytic system in healthy individuals. Subjects (n = 14) were
      administered oxandrolone (10 mg twice daily) for 14 days. Blood was obtained on
      days 0, 1, 3, 7, 9, 14, and then at day 42 (28 days after discontinuation of the
      drug). Samples were analyzed for the plasma plasminogen, plasminogen activator
      inhibitor (PAI-1), fibrinogen, and coagulation factors (II, V, VII, VIII, and X).
      After 7 days of administration of oxandrolone, the plasma plasminogen level
      significantly increased [100% +/- 21% to 174% +/- 21% (P < 0.0001)]. PAI-1 was
      significantly decreased at day 3 [16 +/- 9 to 7 +/- 4 mg/dL (P < 0.01)].
      Coagulation factors II and V significantly increased at day 14 [88 +/- 15 to 122
      +/- 11 (P < 0.005) and 105 +/- 21 to 179 +/- 36% (P < 0.0001)], respectively.
      Factor VII level decreased by day 3 [91% +/- 26% to 83% +/- 18%, NS], but after
      14 days factor VII level returned to baseline (91% +/- 26% to 93% +/- 19%, NS).
      The increase of factor VIII level was not significant (111% +/- 64% to 125% +/-
      55%, NS). Factor X increased steadily over 14 days of drug treatment [96% +/- 11%
      to 107% +/- 25%, NS] and after discontinuation, decreased and returned to
      baseline by day 42 [107% +/- 25% to 89% +/- 25%, NS]. Fibrinogen decreased by 22%
      +/- 12%, (NS). Administration of oxandrolone, to healthy young men was associated
      with a significant increase in select blood coagulation factors and plasminogen.
      These changes create a state of potential hypercoagulability that appears to be
      counterbalanced by increased fibrinolytic activity to maintain homeostasis.

PMID- 16432849
TI  - Hereditary thrombophilia in ethnic Omani patients.
AB  - Hereditary thrombophilias are a group of inherited conditions that predispose to
      thrombosis. Mutations like factor V Leiden, prothrombin gene variant 20210A, and
      hereditary hyperhomocysteinemia are associated with an increased risk for
      thromboembolism as compared to mutations in natural inhibitors of coagulation.
      There is also evidence that multiple defects co-exists in persons with a tendency
      for thrombosis. We studied prothrombotic determinants, namely protein C, protein
      S, and AT along with factor V Leiden (1691G-->A), prothrombin gene mutation
      (20210G-->A), CBS 844ins68 mutation, and MTHFR mutation (677C-->T) in consecutive
      ethnic Omani patients with first episode of a thrombophilic event, namely, deep
      vein thrombosis (DVT), and/or pulmonary embolism (PE) or thrombosis at an unusual
      site. Fasting plasma homocysteine was also analyzed. Factor V Leiden and the
      prothrombin gene mutation were not seen in any patient nor in any control subject
      studied. The thermolabile MTHFR mutation (677C-->T) was present in 14 patients
      (35.89%) whereas the CBS 844ins68 mutation was documented in 6 patients (15.38%);
      3 patients were common in both groups. Six patients had low protein C (15.38%),
      two patients had low protein S (5.12%), but none had low AT levels.
      Interestingly, one patient had triple abnormality, namely, PC deficiency with
      both CBS 844ins68 mutation as well as the MTHFR mutation (677C-->T) whereas
      another two patients had the latter two mutations together. This data set,
      although small, reflects the importance of multiple screening strategies. The
      yield appears high, emphasizing the referral pattern to a tertiary health center.
      Of these patients, 43.58% had either or both the hyperhomocysteinemic mutations
      studied, whereas in 38.46% of these patients, no underlying cause for
      thrombophilia could be documented.

PMID- 16432850
TI  - Constitutive neuregulin-1/ErbB signaling contributes to human vestibular
      schwannoma proliferation.
AB  - Vestibular schwannomas (VSs) are benign tumors that arise from the Schwann cells
      (SCs) lining the vestibular nerve. VS cells survive and proliferate far from
      neurons and axonally derived growth factors. We have previously shown that VSs
      produce the glial growth factor, neuregulin-1 (NRG1), and its receptors, ErbB2
      and ErbB3. In the present work, we explore the contribution of constitutive
      NRG1:ErbB signaling to human VS cell proliferation. We confirm that human VSs,
      which express markers of immature and denervated SCs, also express endogenous
      NRG1 and activated ErbB2. We find that a blocking anti-NRG1 antibody and
      trastuzumab (Herceptin, HCN), a humanized anti-ErbB2 inhibitory monoclonal
      antibody, effectively inhibit NRG1 induced SC proliferation. Treatment of primary
      VS cultures with anti-NRG1 or HCN reduces cell proliferation in the absence of
      exogenous NRG1. Furthermore, conditioned medium from VS cell cultures contains
      NRG1 and stimulates SC proliferation in SC cultures, an effect that is inhibited
      by anti-NRG1 and HCN. These data suggest an autocrine pathway of VS growth
      stimulation involving NRG and ErbB receptors. Inhibition of constitutive NRG:ErbB
      signaling reduces VS cell proliferation in vitro and may have therapeutic
      potential for patients with VSs.

PMID- 16432851
TI  - Helicobacter pylori infection is probably the cause of chronic idiopathic
      neutropenia (CIN)-associated splenomegaly.
AB  - Splenic volume and Helicobacter pylori (H. pylori) infection were evaluated in 67
      patients with chronic idiopathic neutropenia (CIN) and 39 healthy individuals.
      Using ultrasound, splenomegaly was found in 61.7% of H. pylori-infected subjects
      compared to only 8.7% noted in the group of H. pylori-non-infected individuals (P
      < 0.0001). Splenomegaly was also found in 47.8% of CIN patients compared to 12.8%
      in the group of non-CIN subjects (P = 0.0003). However, applying the two-way
      ANOVA test, a statistically significant effect on splenic volume was documented
      for "factor H. pylori " (F1(102) = 16.800, P < 0.0001) but not for "factor CIN"
      (F1(102) = 3.213, P = 0.0760), suggesting that CIN-associated splenomegaly is
      probably due to H. pylori infection.

PMID- 16432852
TI  - Correlation of transfusion volume to change in hematocrit.
AB  - While it has generally been accepted that a 3% change in hematocrit is equivalent
      to a 1-"unit" loss of blood, few studies have been published to actually document
      this. A more complete understanding of this correlation would be helpful in
      estimating blood loss from changes in hematocrit in patients sustaining
      hemorrhage as well as in those receiving transfusions. In this retrospective
      study, we analyzed the post-transfusion alterations in hematocrit from 61
      independent transfusions in 48 different pelvic fracture patients (age range, 16
      62 years). Transfusion volumes were correlated with changes in hematocrit over 24
      hr periods between the 5th and 12th hospital days, a time when there was no
      ongoing hemorrhage in these patients. The average increase in hematocrit per
      liter of packed red blood cells transfused was 6.4% +/- 4.1%. If 1 "unit" of
      packed red blood cells is approximately 300 mL, this becomes a change of
      hematocrit of 1.9% +/- 1.2% per "unit" of blood. The accepted correlation of
      about 1 "unit" of blood loss per 3% change in hematocrit would be valid for a 500
      cc unit, but a typical unit of packed red blood cells is typically 300 cc. In
      addition, the variability is substantial as indicated by our standard deviation.
      Limitations of this study include hematocrit changes due to fluid resuscitation,
      dehydration, age, persistent hemorrhage, and the retrospective nature of the
      evaluation.

PMID- 16432853
TI  - Beta-thalassemia intermedia and Hodgkin lymphoma.

PMID- 16432854
TI  - Diabetes insipidus and thrombocytosis as the presenting symptoms of acute
      myeloblastic leukemia with monosomy 7.

PMID- 16432855
TI  - Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring
      lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS).
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that
      impair the activity of lymphocyte apoptosis proteins, leading to chronic
      lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of
      lymphoma. We investigated the utility of fluorodeoxyglucose positron emission
      tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in
      ALPS. We report that FDG avidity of benign lymph nodes in ALPS can be high and,
      hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide
      the decision for selecting which of many enlarged nodes in ALPS patients to
      biopsy when lymphoma is suspected.

PMID- 16432857
TI  - Burkitt lymphoma of the breast.

PMID- 16432856
TI  - Transformation and progression of Waldenstrom's macroglobulinemia following
      cladribine therapy in two cases: natural evolution or iatrogenic causation?
AB  - We report two cases of Waldenstrom's macroglobulinemia with an unusual aggressive
      transformation following treatment with cladribine (2-chlorodeoxyadenosine, 2
      CdA), a purine analogue. The first patient developed transformation to a diffuse
      large-cell non-Hodgkin lymphoma, while the second developed extensive
      extramedullary involvement. Both patients displayed rapid progression following
      transformation and were refractory to chemotherapy. Both patients were pretreated
      with multiple courses of prednisone and chlorambucil, and transformation occurred
      shortly after therapy with cladribine. We propose that immune suppression from
      alkylating agents and purine analogues may have contributed to the unusual
      progression, resulting in a dismal outcome.

PMID- 16432858
TI  - Vaso-occlusive manifestations in a patient with sickle cell-hemoglobin E (HbSE)
      disease.

PMID- 16432859
TI  - Acrocyanosis as a presenting symptom of Hodgkin lymphoma.

PMID- 16432860
TI  - Autoimmune thyroiditis during thalidomide treatment.

PMID- 16432861
TI  - Dyspnea secondary to pulmonary hematopoiesis as presenting symptom of
      myelofibrosis with myeloid metaplasia.
AB  - We report a case of a patient with myelofibrosis with myeloid metaplasia (MMM)
      who presented with progressive dyspnea of unexplained origin. Splenomegaly, blood
      smear, and bone marrow findings allowed diagnosis of MMM. High-resolution CT
      chest scan revealed diffuse septal thickening, while echocardiography and
      electrocardiogram showed no indirect evidence of pulmonary hypertension. Finally,
      lung biopsy revealed irregularly distributed interstitial fibrosis with islands
      of erythroblasts, immature granulocytic elements, and dysplastic megakaryocytes,
      allowing diagnosis of pulmonary extramedullary hematopoiesis (EMH). The patient
      received hydroxyurea as cytoreductive agent, obtaining a good hematologic
      response and an improvement of dyspnea. Note that, in this patient, dyspnea was
      the first clinical symptom of MMM; the dyspnea was not associated with pulmonary
      hypertension and improved following cytoreductive treatment. This case points to
      the importance of suspecting pulmonary EMH when unexplained progressive dyspnea
      occurs in a patient with MMM. Early recognition of pulmonary EMH may prevent PH
      and favor a better response to therapy.

PMID- 16432862
TI  - Antiproliferation effects of oridonin on HPB-ALL cells and its mechanisms of
      action.
AB  - Oridonin, an ent-kaurane diterpenoid derived from the herbal Rabdosia rubescens,
      has been recently reported to have antitumor effects on a large variety of cancer
      cells. The present study was undertaken to investigate the in vitro
      antiproliferation and apoptosis inducing effects of oridonin on HPB-ALL cell
      lines and its mechanisms of action. HPB-ALL cells in culture medium in vitro were
      treated with different concentrations of oridonin (16-56 micromol/L). MTT assay
      was used to detect the cell growth inhibitory rate, and the cell viability was
      assessed by the trypan blue dye-exclusion method. Cell apoptosis and the
      mitochondrial membrane potential (delta psi m) were investigated by flow
      cytometry (FCM), Hoechst 33258 staining, and DNA fragmentation analysis. The
      expression of caspase-3 and different apoptosis modulators, including Fas and Bcl
      2 family members, was analyzed by Western blotting. The results revealed that
      oridonin could significantly inhibit the growth of HPB-ALL cells and cause
      apoptosis, and the suppression was both time- and dose-dependent. After treatment
      with oridonin for 48 hr, the percentage of disruption of delta psi m gradually
      increased in a dose-dependent manner along with marked changes of cell apoptosis,
      and necrotic cells increased remarkably after the cells were treated with
      oridonin for 72 hr; Western blotting showed cleavage of the caspase-3 zymogen
      protein (32 kDa) with the appearance of its 20-kDa subunit when apoptosis
      occurred; expression of Bcl-2 and Bcl-XL was downregulated remarkably while
      expression of Bax and Bid was upregulated concurrently after the cells were
      treated with oridonin for 24 hr. Of note, the expressions of Fas and other Bcl-2
      family members including Bak and Bad remained constant before and after apoptosis
      occurred. We therefore conclude that oridonin has significant antiproliferation
      effects on HPB-ALL cells by induction of apoptosis as well as directly causing
      cell necrosis and that oridonin-induced apoptosis on HPB-ALL cells is mainly
      related to the disruption of delta psi m and activation of caspase-3 as well as
      downregulation of anti-apoptotic protein Bcl-2, Bcl-XL, and upregulation of pro
      apoptotic proteins Bax and Bid. The results indicate that oridonin may serve as a
      potential antileukemia reagent.

PMID- 16432863
TI  - Misdiagnosis in patients with diclofenac-induced hemolysis: new cases and a
      concise review.
AB  - Diclofenac has been implicated in many cases of life-threatening immune hemolytic
      anemia (IHA). Nevertheless, confusion still occurs at the bedside and in the
      laboratory. Herein we report nine new patients and summarize all published cases
      (total, n = 61). Direct and indirect antiglobulin tests were performed according
      to standard procedures. Tests for drug-dependent antibodies were performed in the
      presence and absence of the target drugs and their ex vivo antigens (in the urine
      of patients treated with the drug). Diclofenac- and/or ex-vivo-antigen-dependent
      red cell antibodies were detected in all new cases. We identified nine new cases
      with diclofenac-dependent IHA. All cases were initially suspected to have an
      abdominal illness and/or autoimmune hemolytic anemia of warm type. Acute renal
      failure was present in three of the 9 new patients and in 20 of 37 published
      patients. Seven of the 46 patients died (15%), and clinical information is
      lacking in 15 other published cases. Diclofenac-dependent and/or ex-vivo-antigen
      dependent IHA should always be considered when a patient on diclofenac develops
      acute renal failure and/or IHA.

PMID- 16432864
TI  - Successful rapid discontinuation of immunosuppressive therapy at molecular
      relapse after allogeneic bone marrow transplantation in a pediatric patient with
      myelodysplastic syndrome.
AB  - The success of allogeneic bone marrow transplantation (allo-BMT) in children with
      myelodysplastic syndrome (MDS) is mainly affected by relapse. The role of
      additional immunotherapy for pediatric patients with MDS relapsing after allo-BMT
      remains to be established. Because immunotherapy is generally more effective for
      patients who bear a low tumor burden, monitoring of minimal residual diseases
      (MRD) is essential for early diagnosis at molecular relapse. We report here that
      a patient with relapsed MDS after allo-BMT was successfully treated by the rapid
      discontinuation of immunosuppressive therapy at molecular relapse while
      monitoring Wilms tumor (WT1) gene expression levels. Quantitative analysis of WT1
      gene expression appeared to be a useful tool to monitor MRD in the present case.

PMID- 16432865
TI  - Interferon-alpha therapy for chronic myeloid leukemia during pregnancy.

PMID- 16432866
TI  - Successful therapy with whole-lung lavage and autologous peripheral blood stem
      cell transplantation for pulmonary alveolar proteinosis complicating acute
      myelogenous leukemia.
AB  - A 43-year-old man with acute myelogenous leukemia (AML) was found to be
      complicated with pulmonary alveolar proteinosis (PAP), which was confirmed by
      biochemical and histological findings. After achievement of complete remission of
      AML, he underwent whole-lung lavages twice between intensive chemotherapies.
      Subsequently, he received high-dose chemotherapy and autologous peripheral blood
      stem cell transplantation (PBSCT), which was performed safely without any
      infections. He has been in remission for 25 months after transplant with no
      recurrence of PAP. Autologous PBSCT in combination with whole-lung lavage may be
      a promising strategy in the treatment of PAP associated with hematological
      malignancies.

PMID- 16432867
TI  - Transient monoclonal gammopathy in a patient with Bartonella quintana
      endocarditis.
AB  - Monoclonal gammopathy has been reported rarely in association with infectious
      diseases. Viral infection has been the most frequently reported. We report a case
      of Bartonella quintana endocarditis in a 45-year-old homeless male associated
      with a monoclonal IgG kappa gammopathy. The gammopathy disappeared after 8 months
      of antibiotics while the Bartonella antibody titre was decreasing. This
      correlation suggests a causative role for B. quintana for the monoclonal
      gammopathy. To the best of our knowledge, this the first report of monoclonal
      gammopathy in the course of B. quintana infection.

PMID- 16432868
TI  - Kikuchi-Fujimoto disease: a rare but important cause of fever and lymphadenopathy
      in pregnant women.
AB  - We report a case of Kikuchi-Fujimoto disease (KFD) in a 28-year-old pregnant
      woman with prolonged fever and generalized lymphadenopathy. We evaluated the
      patient for etiology of the fever and adenopathy, which were unresponsive to
      antibiotic therapy. Cervical lymph node histology showed KFD. Currently, there is
      scant data available regarding the course and treatment of KFD during pregnancy.
      We administered steroid therapy (prednisone 1 mg/kg/day) to control severe
      systemic and constitutional symptoms. We observed a reduction in lymph node size
      as well as abatement of fever and other constitutional symptoms. The patient
      carried the fetus to full term with no apparent adverse effect. Our experience
      showed that steroid therapy may be used effectively to control KFD-related
      symptoms after the first 16 weeks without terminating the pregnancy.

PMID- 16432869
TI  - Acquired amegakaryocytic thrombocytopenic purpura.
AB  - Acquired amegakaryocytic thrombocytopenia is an unusual hematologic disorder
      characterized by thrombocytopenia in association with markedly diminished bone
      marrow megakaryocytes. We report a case that responded to treatment with
      cyclosporine but not to IL-11. The bone marrow biopsy, repeated after resolution
      of thrombocytopenia, showed normal number of megakaryocytes.

PMID- 16432870
TI  - Bilateral adrenal hemorrhage associated with essential thrombocytosis.

PMID- 16432871
TI  - Hodgkin lymphoma with leptomeningeal involvement.

PMID- 16432872
TI  - Comment on flow-cytometric analysis of neutrophils.

PMID- 16432873
TI  - Mutation screening in the human epsilon-globin gene using single-strand
      conformation polymorphism analysis.
AB  - The human epsilon-globin gene is necessary for primitive human erythropoiesis in
      the yolk sac. Herein we report a non-radioactive single-strand conformation
      polymorphism (SSCP) approach to screen the human epsilon-globin gene and its
      regulatory regions for possible mutations and single-nucleotide polymorphisms in
      normal adult subjects, in order to determine those genomic regions, which are not
      necessary for its proper regulation and function. We identified no sequence
      variations apart from the expected 5'epsilon /HincII polymorphism in the
      fragments analyzed, suggesting that genomic alterations in the epsilon-globin
      gene are most likely incompatible with normal erythropoiesis and proper embryonic
      development.

PMID- 16432874
TI  - Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host
      disease: a case report.
AB  - Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogenic
      bone marrow transplantation. Even with aggressive treatment, cGVHD is associated
      with a significant degree of morbidity and mortality. cGVHD resembles autoimmune
      disorder, particularly systemic sclerosis (SSc). Sarpogrelate hydrochloride (SH)
      is an antagonist of the 5-hydroxytryptamine2A (5HT2A) receptor and has been
      reported to be effective in the treatment of systemic sclerosis (SSc) patients
      with Raynaud phenomenon. We used SH to treat a cGVHD patient, and we measured
      plasma PDGF and total TGF-beta levels. After SH treatment, his plasma PDGF and
      total TGF-beta levels decreased, and he noticed improvement in his skin
      pigmentation. In the present case, SH may have improved the skin lesion by
      inhibiting the synthesis of PDGF and TGF-beta.

PMID- 16432875
TI  - A two-phase analysis of solute partitioning into the stratum corneum.
AB  - An analysis is presented of partition coefficients K(SC/w) describing solute
      distribution into fully hydrated stratum corneum (SC) from dilute aqueous
      solution (w). A comprehensive database is compiled from the experimental
      literature covering more than eight decades in the octanol/water partition
      coefficient K(o/w). It is analyzed according to a two-phase model following that
      of Anderson, Raykar, and coworkers (1988, 1989), which accounts for uptake by
      intercellular lipid and corneocyte (keratin plus water) phases having inherently
      different lipophilicities, as characterized by an SC lipid/water partition
      coefficient K(lip/w) and a partition coefficient PC(pro/w) quantifying
      cornoeocyte-phase binding. Regression of 72 data points yields useful best-fit
      recalibrations of power laws (or linear free energy relationships) giving
      K(lip/w) and PC(pro/w) as functions of K(o/w). The specific conclusions of the
      analysis are as follows: (i) The two-phase model offers substantial improvements
      over previously proposed analytical representations of K(SC/w), yielding an rms
      error in log(10)K(SC/w) of 0.30 limited by the scatter in the data. (ii) The best
      fit description of the lipid phase is given by the power law K(lip/w) = 0.43
      (K(o/w))(0.81), suggesting about half the absolute value of K(lip/w) relative to
      previous estimates. (iii) The best-fit description of corneocyte-phase binding
      differs negligibly from the correlation found by Anderson, Raykar, and coworkers
      for the more limited set of compounds studied by them. Explicit consideration of
      the two-phase nature of the SC also furnishes a rational basis for predicting the
      effects of varying hydration state upon K(SC/w).

PMID- 16432876
TI  - Polymorphic transformation of indomethacin under high pressures.
AB  - To study the effect of pressure on polymorphic transformation, intact powder, and
      ethanol slurry of alpha, gamma, and amorphous forms of indomethacin (IMC) were
      compressed under high pressures. A quantifying method for the percentages of
      these three constituents in sample powder was established. Using this method,
      analysis of compressed samples revealed that alpha form, which is difficult to
      prepare in stable form under atmospheric pressure, was easily obtained in stable
      form from the ethanol slurry of the amorphous IMC, which does not include any
      specific crystalline forms. In the ethanol slurry of gamma form, transformation
      to alpha form was observed: a reciprocal phenomenon under atmospheric pressure.
      These results can be rationally explained as follows: alpha form is more easily
      crystallized than gamma form in the ethanol solution, the more closely-packed
      crystal structure of alpha form is thermodynamically predominant over gamma form
      under high pressure, and pressure-induced amorphization occurs. This study
      indicates that crystallization experiments from the slurry of amorphous samples
      under various pressures can be useful in screening polymorphic or other solid
      states.

PMID- 16432877
TI  - A topological substructural approach for the prediction of P-glycoprotein
      substrates.
AB  - A topological substructural molecular design approach (TOPS-MODE) has been used
      to predict whether a given compound is a P-glycoprotein (P-gp) substrate or not.
      A linear discriminant model was developed to classify a data set of 163 compounds
      as substrates or nonsubstrates (91 substrates and 72 nonsubstrates). The final
      model fit the data with sensitivity of 82.42% and specificity of 79.17%, for a
      final accuracy of 80.98%. The model was validated through the use of an external
      validation set (40 compounds, 22 substrates and 18 nonsubstrates) with a 77.50%
      of prediction accuracy; fivefold full cross-validation (removing 40 compounds in
      each cycle, 80.50% of good prediction) and the prediction of an external test set
      of marketed drugs (35 compounds, 71.43% of good prediction). This methodology
      evidenced that the standard bond distance, the polarizability and the Gasteiger
      Marsilli atomic charge affect the interaction with the P-gp; suggesting the
      capacity of the TOPS-MODE descriptors to estimate the P-gp substrates for new
      drug candidates. The potentiality of the TOPS-MODE approach was assessed with a
      family of compounds not covered by the original training set (6
      fluoroquinolones), and the final prediction had a 77.7% of accuracy. Finally, the
      positive and negative substructural contributions to the classification of 6
      fluoroquinolones, as P-gp substrates, were identified; evidencing the
      possibilities of the present approach in the lead generation and optimization
      processes.

PMID- 16432878
TI  - DNA acts as a nucleation site for transient cavitation in the ultrasonic
      nebulizer.
AB  - Several new technologies based upon ultrasound technology have been proposed as a
      method to enhance the delivery of genetic therapeutics. Using ultrasonic
      nebulization and a well-established method to quantitatively monitor transient
      cavitation, this study investigates the extent and factors influencing the
      degradation of DNA. Results from our studies show that the presence of DNA
      greatly enhances cavitation, and that the number of transient cavitation events
      also increases with the hydrodynamic diameter and number of DNA molecules in
      solution. More importantly, removing saturated gases from the plasmid DNA
      solutions resulted in a decrease in transient cavitation events but not
      degradation rate, suggesting that the cavitation event responsible for
      degradation occurs locally at the DNA molecule. Finally, complexing plasmid DNA
      with the cationic polymer polyethylenimine protected the native structure by
      reducing the molecule's potential to act as a heterogeneous nucleation site for
      transient cavitation.

PMID- 16432880
TI  - The determinants of stability in the human prion protein: insights into folding
      and misfolding from the analysis of the change in the stabilization energy
      distribution in different conditions.
AB  - The dynamic evolution of the PrP(C) from its NMR-derived conformation to a beta
      sheet-rich, aggregation-prone conformation is studied through all-atom, explicit
      solvent molecular dynamics in different temperature and pH conditions. The
      trajectories are analyzed by means of a recently introduced energy decomposition
      approach aimed at identifying the key residues for the stabilization and folding
      of the protein. It is shown that under native conditions the stabilization energy
      is concentrated in regions of the helices H1 and H3, whereas under misfolding
      conditions (low pH, high temperature, or mutations in selected sites) it is
      spread out over helix H2. Misfolding appears to be a rearrangement of the chain
      that disrupts most of the native secondary structure of the protein, producing
      some beta-rich conformations with an energy distribution similar to that of the
      native state.

PMID- 16432879
TI  - Two distinct heme distal site states define Cerebratulus lacteus mini-hemoglobin
      oxygen affinity.
AB  - The nerve tissue hemoglobin of Cerebratulus lacteus (CerHb) is the smallest
      naturally occurring known hemoglobin. Stabilization of the diatomic bound species
      (e.g., O(2)) is achieved through a network of hydrogen bonds based on three key
      residues TyrB10, GlnE7, and ThrE11. The first two residues are typically
      associated in hemoglobins with enhanced O(2) affinity, related to hydrogen bond
      stabilization of the heme-bound O(2) resulting in a decrease of the ligand
      dissociation rates. In contrast to the above observations, the affinity of CerHb
      for O(2) is only moderate, and the rate of O(2) dissociation is unexpectedly
      high. To gain insight on the diverse molecular mechanisms controlling ligand
      affinities, we have analyzed w.t. CerHb and its ThrE11-->Val mutant by means of
      joint molecular dynamics and quantum mechanics simulation techniques,
      complementing recent site-directed mutagenesis experiments. Our results suggest
      that the observed O(2) dissociation rates can only be explained through a dynamic
      equilibrium between high and low affinity states of the w.t. CerHb heme distal
      site.

PMID- 16432881
TI  - Immunohistochemical targeting of sea anemone cytolysins on tentacles, mesenteric
      filaments and isolated nematocysts of Stichodactyla helianthus.
AB  - The toxicity of biomolecules obtained from sea anemones in vitro does not
      necessarily justify their function as toxins in the physiology of the anemone.
      That is why anatomical and physiological considerations must be taken into
      account in order to define their physiological role in the organism. In this
      work, antibodies generated to Sticholysin II, a cytolysin produced by the
      Caribbean Sea anemone Stichodactyla helianthus, are used as specific markers to
      explore the sites of production and storage of the cytolysin in the sea anemone.
      The immunoperoxidase staining developed gave specific dark-brown staining in
      tentacles and mesenteric filaments as well as in basitrichous nematocysts
      isolated from tentacles of S. helianthus. These results support the role of these
      proteins as toxins in the physiology of the anemone, especially in functions such
      as in predation, defense and digestion.

PMID- 16432882
TI  - Differentiation and development of testis in the oviparous lizard, Calotes
      versicolor (Daud.).
AB  - The differentiation and development of the testis in the lizard Calotes
      versicolor was studied histologically and histoenzymatically from the day of
      oviposition (stage 27) to 2 months after hatching. The study reveals the
      appearance of the gonadal component as a genital ridge at stage 27. The first
      sign of testis differentiation is observed at stage 33, which displays a well
      developed medulla consisting of seminiferous cords comprising Pre-Sertoli cells.
      The sex differentiation of the embryonic gonads occurs at stage 34. At this
      stage, seminiferous cords of the testis are prominent and extensive with many pre
      Sertoli cells and few spermatogonia. The interstitial space consists of immature
      fibroblast-type Leydig cells. Pre-Sertoli cells of the seminiferous cords
      differentiate into Sertoli cells with a triangular nucleus becoming apparent
      around stages 36-37. The fibroblast-like Leydig cells differentiate into round
      matured Leydig cells at stage 40. Quantitative estimation of germ cells reveals
      that the number of germ cells increases in individual gonads, and in 5-day-old
      hatchling's, this number multiplies by manifold. Spermatogonia show reductional
      division in the testis of 1-day-old hatchlings. Histochemical localization of
      Delta5-3beta-HSDH and G-6-PDH activity appears in the seminiferous cords
      (medulla) of the testis after sexual differentiation (stage 36), indicating that
      the embryonic medulla is the site of steroidogenesis and not the cortex in C.
      versicolor. This study also suggests that morphological differentiation of the
      gonad precedes detectable steroidogenesis in this species. In 10-day-old
      hatchling's, Delta5-3beta-HSDH activity is seen in the interstitial cells of the
      testis, which, however, is not detected in the seminiferous tubules. The
      intensity of the enzyme activity remains more or less the same in the testis up
      to 10 days after hatching and begins to increase thereafter. The increase in
      steroidogenesis parallels the progressive post-hatching increase of the
      interstitial/Leydig cells.

PMID- 16432883
TI  - 65Zn2+ Transport by lobster hepatopancreatic lysosomal membrane vesicles.
AB  - In crustaceans, the hepatopancreas is the major organ system responsible for
      heavy metal detoxification, and within this structure the lysosomes and the
      endoplasmic reticulum are two organelles that regulate cytoplasmic metal
      concentrations by selective sequestration processes. This study characterized the
      transport processes responsible for zinc uptake into hepatopancreatic lysosomal
      membrane vesicles (LMV) and the interactions between the transport of this metal
      and those of calcium, copper, and cadmium in the same preparation. Standard
      centrifugation methods were used to prepare purified hepatopancreatic LMV and a
      rapid filtration procedure, to quantify 65Zn2+ transfer across this organellar
      membrane. LMV were osmotically reactive and exhibited a time course of uptake
      that was linear for 15-30 sec and approached equilibrium by 300 sec. 65Zn2+
      influx was a hyperbolic function of external zinc concentration and followed
      Michaelis-Menten kinetics for carrier transport (Km = 32.3 +/- 10.8 microM; Jmax
      = 20.7 +/- 2.6 pmol/mg protein x sec). This carrier transport was stimulated by
      the addition of 1 mM ATP (Km = 35.89 +/- 10.58 microM; Jmax = 31.94+/-3.72
      pmol/mg protein/sec) and replaced by an apparent slow diffusional process by the
      simultaneous presence of 1 mM ATP+250 microM vanadate. Thapsigargin (10 microM)
      was also a significant inhibitor of zinc influx (Km = 72.87 +/- 42.75 microM;
      Jmax =22.86 +/- 4.03 pmol/mg protein/sec), but not as effective in this regard as
      was vanadate. Using Dixon analysis, cadmium and copper were shown to be
      competitive inhibitors of lysosomal membrane vesicle 65Zn2+ influx by the ATP
      dependent transport process (cadmium Ki = 68.1 +/- 3.2 microM; copper Ki = 32.7
      +/- 1.9 microM). In the absence of ATP, an outwardly directed H+ gradient
      stimulated 65Zn2+ uptake, while a proton gradient in the opposite direction
      inhibited metal influx. The present investigation showed that 65Zn2+ was
      transported by hepatopancreatic lysosomal vesicles by ATP-dependent, vanadate-,
      thapsigargin-, and divalent cation-inhibited, carrier processes that illustrated
      Michaelis-Menten influx kinetics and was stimulated by an outwardly directed
      proton gradient. These transport properties as a whole suggest that this
      transporter may be a lysosomal isoform of the ER Sarco-Endoplasmic Reticulum
      Calcium ATPase.

PMID- 16432884
TI  - Low-molecular-weight vitellogenin 1-like proteins are components of a UV-damaged
      DNA binding activity highly expressed in zebrafish (Danio rerio) embryos.
AB  - A strong UV-damaged-DNA binding activity had been detected in the extracts of
      zebrafish embryos at 12 hr after fertilization by gel shift assay (Hsu et al.
      2002. Fish Physiol Biochem 25:41-51). We attempted to study the components of
      this binding activity and their importance in DNA damage recognition. Among the
      proteins extracted from gel retardation complexes, a 30- and a 35-kDa polypeptide
      binding preferentially to 6-4photoproducts (6-4PPs) generated by UV irradiation
      were identified by peptide mass fingerprinting (PMF) as homologs of zebrafish
      vitellogenin I (zfVg1), a 150-kDa metalloprotein known as the precursor of yolk
      proteins in embryos. zfVg1-like polypeptides ranging from 25 to 105 kDa were
      detected in 12- and 96-hr-old zebrafish extracts by immunoblot analysis.
      Immunoblot analysis of affinity-captured proteins confirmed the preferential
      binding of the 30-35-kDa polypeptides to the 6-4PP probe, while 96-hr-old larval
      extracts containing very low levels of these two factors failed to recognize 6
      4PPs. The presence of zfVg1-like factors was important in maintaining the
      embryonic UV-binding activity, as inclusion of a monoclonal anti-zfVg1 antibody
      in reaction mixtures caused a concentration-dependent reduction in 6-4PP-specific
      binding. In contrast, DNA damage recognition was not disturbed at all by an anti
      HSP 70 antibody. The formation of 6-4PP-binding complexes was abolished after the
      addition of the metal chelating agent 1,10-phenanthroline (OP) to zebrafish
      extracts and the loss of UV-binding capacity correlated with the disappearance of
      the 35-kDa factor in OP-treated extracts. Our results demonstrated the ability of
      low-molecular-weight zfVg1-like proteins in zebrafish embryos to bind UV-damaged
      DNA and the expression of this embryonic UV-binding activity was metal dependent.
      Whether zfVg1-like UV-binding proteins are involved in repairing damaged DNA in
      embryos or in processing helical structures similar to UV-distorted DNA needs
      further investigation.

PMID- 16432885
TI  - Thyroid and hypoxic stress in the newt Triturus carnifex.
AB  - When specimens of the newt Triturus carnifex, under anaesthesia by submersion in
      a 0.2% chlorbutol solution for 25 min, are isolated in a respiratory chamber at
      18 degrees C containing water with only 1.3 ppm of oxygen, they consume the
      oxygen completely in about 3 hr, but they can stay alive for many more hours and
      wake up with no apparent exterior consequences. Hypoxia induces rapid onset of
      hepatic steatosis and melanosis, as well as a controlled haemolytic process
      involving a pool of red blood cells of the same order of size as that held as a
      reserve in the spleen by animals in an aerial habitat. At the origin of the
      phenomena is an intense response by the hypophysis, histologically detectable 1
      hr from the onset of treatment and confirmed 2 hr later by a highly significant
      increase in the plasma thyroidstimulating hormone (TSH) concentration compared
      with the controls (41.5 +/- 13.7 microU/L vs. 15.5 +/- 6.2; P < 0.005). The
      thyroid follicles react by reabsorbing their colloid, but instead of an increase
      in the plasma free T3 and T4 concentrations, fT3 falls significantly (1.5 +/- 0.3
      pg/mL vs., the 2.4 +/- 0.7; P < 0.05), whereas fT4 remains stationary (4.0 +/-
      0.5 pg/mL vs. 4.6 +/- 0.8; N.S.). After 6 hr, the plasmatic TSH concentration is
      still higher than in the controls (27.0 +/- 3.0 microU/L vs. 15.5 +/- 6.2; P <
      0.05), whereas fT3 and fT4 remain stable (1.5 +/- 0.3 and 4.4 +/- 0.5 pg/mL,
      respectively). If T3 or T4 labelled with 125I is administered prior to hypoxia,
      after 6 hr of treatment the radioactivity is found to be limited exclusively to
      the liver and kidney; the thyroid, gall bladder and gut result negative, and this
      does not agree with hypotheses of hormone inactivation by deiodination,
      sulphation or glucuronidation. This apparently peculiar endocrine path has not
      been observed in previous studies on hypoxia in vertebrates, because the
      experiments were always designed to analyse plasma hormone levels after at least
      24 hr of hypoxia or during chronic treatments, losing the most interesting phases
      of the endocrine response. The possibility that the hypoxic newt possesses
      alternative or complementary metabolic pathways to anaerobic glycolysis to
      sustain steatogenesis and melanogenesis and maintain the same cardiac activity as
      the controls is briefly discussed.

PMID- 16432886
TI  - Gill area, permeability and Na+ ,K+ -ATPase activity as a function of size and
      salinity in the blue crab, Callinectes sapidus.
AB  - Juvenile blue crabs, Callinectes sapidus, extensively utilize oligohaline and
      freshwater regions of the estuary. With a presumptively larger surface-area-to
      body weight ratio, juvenile crabs could experience osmo- and ionoregulatory costs
      well in excess of that of adults. To test this hypothesis, crabs ranging over
      three orders of magnitude in body weight were acclimated to either sea water
      (1,000 mOsm) or dilute sea water (150 mOsm), and gill surface area, water and
      sodium permeabilities (calculated from the passive efflux of 3H2O and 22Na+),
      gill Na+, K+ -ATPase activity and expression were measured. Juveniles had a
      relatively larger gill surface area; weight-specific gill surface area decreased
      with body weight. Weight-specific water and sodium fluxes also decreased with
      weight, but not to the same extent as gill surface area; thus juveniles were able
      to decrease gill permeability slightly more than adults upon acclimation to
      dilute media. Crabs < 5 g in body weight had markedly higher activities of gill
      Na+ ,K+ -ATPase than crabs > 5 g in both posterior and anterior gills.
      Acclimation to dilute medium induced increased expression of Na+, K+ -ATPase and
      enzyme activity, but the increase was not as great in juveniles as in larger
      crabs. The increased weight-specific surface area for water gain and salt loss
      for small crabs in dilute media presents a challenge that is incompletely
      compensated by reduced permeability and increased affinity of gill Na+, K+ 
      ATPase for Na+. Juveniles maintain osmotic and ionic homeostasis by the
      expression and utilization of extremely high levels of gill Na+, K+ -ATPase, in
      posterior, as well as in anterior, gills.

PMID- 16432887
TI  - Ontogeny of suction feeding capacity in snook, Centropomus undecimalis.
AB  - The ontogeny of suction feeding performance, as measured by peak suction
      generating capacity, was studied in the common snook, Centropomus undecimalis.
      Suction pressure inside the buccal cavity is a function of the total expansive
      force exerted on the buccal cavity distributed across the projected area of the
      buccal cavity. Thus, the scaling exponent of peak suction pressure with fish
      standard length was predicted to be equal to the scaling exponent of
      sternohyoideus muscle cross-sectional area, found to be 1.991, minus the scaling
      exponent for the projected buccal cavity area, found to be 2.009, equal to 
      0.018. No scaling was found in peak suction pressure generated by 12 snook
      ranging from 94 to 314 mm SL, supporting the prediction from morphology. C.
      undecimalis are able to generate similar suction pressures throughout ontogeny.

PMID- 16432888
TI  - Mercury toxicity in the shark (Squalus acanthias) rectal gland: apical CFTR
      chloride channels are inhibited by mercuric chloride.
AB  - In the shark rectal gland, basolateral membrane proteins have been suggested as
      targets for mercury. To examine the membrane polarity of mercury toxicity, we
      performed experiments in three preparations: isolated perfused rectal glands,
      primary monolayer cultures of rectal gland epithelial cells, and Xenopus oocytes
      expressing the shark cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel. In perfused rectal glands we observed: (1) a dose-dependent
      inhibition by mercury of forskolin/3-isobutyl-1-methylxanthine (IBMX)-stimulated
      chloride secretion; (2) inhibition was maximal when mercury was added before
      stimulation with forskolin/IBMX; (3) dithiothrietol (DTT) and glutathione (GSH)
      completely prevented inhibition of chloride secretion. Short-circuit current
      (Isc) measurements in monolayers of rectal gland epithelial cells were performed
      to examine the membrane polarity of this effect. Mercuric chloride inhibited Isc
      more potently when applied to the solution bathing the apical vs. the basolateral
      membrane (23 +/- 5% and 68 +/- 5% inhibition at 1 and 10 microM HgCl2 in the
      apical solution vs. 2 +/- 0.9% and 14 +/- 5% in the basolateral solution). This
      inhibition was prevented by pre-treatment with apical DTT or GSH; however, only
      the permeant reducing agent DTT reversed mercury inhibition when added after
      exposure. When the shark rectal gland CFTR channel was expressed in Xenopus
      oocytes and chloride conductance was measured by two-electrode voltage clamping,
      we found that 1 microM HgCl2 inhibited forskolin/IBMX conductance by 69.2 +/-
      2.0%. We conclude that in the shark rectal gland, mercury inhibits chloride
      secretion by interacting with the apical membrane and that CFTR is the likely
      site of this action.

PMID- 16432889
TI  - Oleic acid uptake by in vitro English sparrow skeletal muscle.
AB  - Studies of prolonged avian flight have shown it to require large amounts of
      energy supplied mainly by free fatty acids (FFA). In the present study, the high
      levels of plasma ketone bodies found in sparrows (2.58 mmol l(-1)) are supportive
      of the use of fatty acids for flight. To determine the nature of fatty acid
      (oleic acid, OA) uptake, various pharmacological agents were used. The uptake of
      OA was examined using the extensor digitorum communis (EDC) muscle of English
      sparrows incubated in vitro. Initial studies demonstrated that radiolabeled OA
      uptake decreased in the presence of increasing unlabeled OA, suggesting that
      uptake occurred by a facilitative transport process. To further characterize OA
      uptake, EDC muscles were incubated with either: insulin (2 ng ml(-1)), insulin
      like growth factor isoform-1 (IGF-I; 48 ng ml(-1)), 5'-Aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR; 2 mmol) or caffeine (5 mmol).
      Insulin, but not IGF-I, significantly increased OA uptake by avian EDC (P <
      0.01). Caffeine and AICAR were ineffective at increasing OA uptake. A specific
      inhibitor of FFA transport by fatty acid transporters (FAT/CD36), sulfo-N
      succinimidyl oleate (SSO; 500 micromoles), significantly decreased OA uptake at
      2.5 min. The effectiveness of SSO suggests that a FAT/CD36-like protein is
      expressed in avian tissues. As uptake of OA was not completely blocked by SSO, it
      is likely that other mechanisms for FFA movement across membranes, such as
      diffusion, may be present.

PMID- 16432890
TI  - Sperm nuclear basic proteins of two closely related species of Scorpaeniform fish
      (Sebastes maliger, Sebastolobus sp.) with different sexual reproduction and the
      evolution of fish protamines.
AB  - In this paper, we present a review of sperm nuclear basic proteins (SNBPs) in
      teleost fish. The distribution of the three basic groups of SNBPs [histone (H)
      type, protamine-like (PL)-type and protamine (P)-type], their evolution and
      possible relation to the mode of fertilization are described. In this regard, we
      have characterized the SNBPs from two closely related species of Scorpaeniform
      fish: internally fertilizing Sebastes maliger and externally fertilizing
      Sebastolobus sp., both in the family Scorpaenidae. Despite the different
      reproductive behavior of these two closely related rockfish species, in both
      instances the SNBP consists of protamines. However, there is a significant
      increase in the arginine content of the protamine in the internally fertilizing
      rockfish. The relevance of this observation is discussed within the context of
      the P-type SNBP in teleosts. The rapid evolution of teleost protamines, including
      those in rockfish, has also allowed us to obtain a molecular phylogeny for this
      group of bony fish that is almost indistinguishable from that currently available
      from the use of conventional anatomical/paleontological markers.

PMID- 16432891
TI  - Impairment of spermatogenesis and enhancement of testicular germ cell apoptosis
      induced by exogenous all-trans-retinoic acid in adult lizard Podarcis sicula.
AB  - In mammals, retinoic acid is involved in the regulation of testicular function by
      interaction with two families of nuclear receptors, retinoic acid receptor (RAR)
      and retinoid X receptor (RXR). Among RAR isoforms, the testicular cells of the
      lizard were found to express only RARalpha (3.7 kb) and RARbeta (3.4 kb) mRNAs,
      as reported here. In this study, the effects of exogenous all-trans-retinoic acid
      (atRA) on spermatogenesis of a non-mammalian seasonal reproducer were
      investigated. Daily intraperitoneal injections of atRA or atRA plus testosterone
      (atRA+T) were given for 2 weeks to adult males of the lizard Podarcis sicula. In
      animals treated with atRA, the seminiferous tubules were markedly reduced in
      cross-area. The seminiferous epithelium collapse was responsible for a sensible
      reduction in the number of germ cells and disruption in normal epithelial
      organization. In comparison, in atRA+T-treated lizards the loss of germinal cells
      was significantly less. The loss of germ cells observed in both experimental
      groups results from an induction of apoptotic process, as revealed by TUNEL
      analysis. Although low in number, apoptotic germ cells were also observed in the
      control groups (saline- and T-treated lizard), where the main germ cells
      undergoing apoptosis are primary spermatocytes (most frequently) and some
      spermatogonia. In conclusion, it is shown here that retinoic acid has deleterious
      effects on lizard spermatogenesis, causing a severe depletion of seminiferous
      epithelium, probably via induction of apoptotic processes. These effects are not
      completely inhibited by simultaneous administration of testosterone, although
      this hormone, once injected, is able to stimulate spermatogenesis and protect
      germinal cells from apoptotic cell death.

PMID- 16432892
TI  - Molecular characterization of a cDNA encoding vitellogenin in the banana shrimp,
      Penaeus (Litopenaeus) merguiensis and sites of vitellogenin mRNA expression.
AB  - In order to determine the primary structure of banana shrimp, Penaeus
      merguiensis, vitellogenin (Vg), we previously purified vitellin (Vt) from the
      ovaries of vitellogenic females, and chemically analyzed the N-terminal amino
      acid sequence of its 78 kDa subunit. In this study, a cDNA from this species
      encoding Vg was cloned based on the N-terminal amino acid sequence of the major
      78 kDa subunit of Vt and conserved sequences of Vg/Vt from other crustacean
      species. The complete nucleotide sequence of Vg cDNA was achieved by RT-PCR and
      5' and 3' rapid amplification of cDNA ends (RACE) approaches. The full-length Vg
      cDNA consisted of 7,961 nucleotides. The open reading frame of this cDNA encoding
      a precursor peptide was comprised of 2,586 amino acid residues, with a putative
      processing site, R-X-K/R-R, recognized by subtilisin-like endoproteases. The
      deduced amino acid sequence was obtained from the Vg cDNA and its amino acid
      composition showed a high similarity to that of purified Vt. The deduced primary
      structure, of P. merguiensis Vg was 91.4% identical to the Vg of Penaeus
      semisulcatus and was also related to the Vg sequences of six other crustacean
      species with identities that ranged from 86.9% to 36.6%. In addition, the amino
      acid sequences corresponding to the signal peptide, N-terminal region and C
      terminal region of P. merguiensis Vg were almost identical to the same sequences
      of the seven other reported crustacean species. Results from RT-PCR analysis
      showed that Vg mRNA expression was present in both the ovary and hepatopancreas
      of vitellogenic females but was not detected in other tissues including muscle,
      heart, and intestine of females or in the hepatopancreas of mature males. These
      results indicate that the Vg gene may be expressed only by mature P. merguiensis
      females and that both the ovary and hepatopancreas are possible sites for Vg
      synthesis in this species of shrimp.

PMID- 16432896
TI  - Reduction kinetics of As (V) to As (III) by a dissimilatory arsenate-reducing
      bacterium, Bacillus sp. SF-1.
AB  - This study proposes a kinetic model that accounts for the toxicity of both
      arsenate and arsenite and characterizes the arsenate reduction ability of a
      dissimilatory arsenate-reducing bacterium, Bacillus sp. SF-1 as a bioremediation
      agent. The model results correlated well with a series of batch reduction
      experiments conducted anaerobically in serum bottles with initial arsenate
      concentrations of 360, 735, and 1,500 mg-As/L. The reduction rate was expressed
      by the Haldane equation that describes the inhibitory effect of high
      concentrations of arsenate. The reduction rate constant k(r), half saturation
      constant K(S), and inhibition constant K(I) were estimated respectively as 1.2 x
      10(9) mg-As/cells/h, 1.5 x 10(2) mg-As/L, and 4.2 x 10(2) mg-As/L. Lethal effects
      of arsenite that is accumulated as the end-product of arsenate reduction were
      expressed by the first-order term with a lethal constant of 2.7 x 10(-4) L/mg
      As/h. The yield for the bacterial cells by arsenate respiration was estimated at
      4.0 x 10(8) cells/mg-As.

PMID- 16432895
TI  - Enhancing recombinant glycoprotein sialylation through CMP-sialic acid
      transporter over expression in Chinese hamster ovary cells.
AB  - Glycosylation engineering strategies that are currently used to improve quality
      of recombinant glycoproteins involve the manipulation of glycosyltransferase
      and/or glycosidase expression. We explored the possibility that over expressing
      nucleotide sugar transporters, particularly the CMP-sialic acid transporter (CMP
      SAT) would improve the sialylation process in Chinese hamster ovary cells (CHO).
      Our hypothesis was that increasing CMP-SAT in the cells through recombinant means
      would increase the transport of CMP-sialic acid into the Golgi, resulting in an
      increased CMP-sialic acid intra-lumenal pool and increased sialylation of the
      proteins produced. We report the construction of the CMP-SAT expression vector
      (pcDNA-SAT) using hamster CMP-SAT (GenBank accession number Y12074) and
      demonstrated its functionality using Lec2 CHO mutant cells. Transfection of pcDNA
      SAT into CHO IFN-gamma, a CHO cell line producing recombinant human interferon
      gamma (IFN-gamma) resulted in single clones that had 2-20 fold increase in total
      CMP-SAT expression at the transcript level and 1.8-2.8 fold increase in CMP-SAT
      at the protein level when compared to untransfected parent CHO IFN-gamma. This
      resulted in 4%-16% increase in site sialylation of IFN-gamma. There was also a
      higher proportion of the more sialylated IFN-gamma glycans produced by the
      clones. We have thus established a novel strategy for sialylation improvement in
      recombinant protein production that can be considered singly or along with
      existing glycosylation improvement strategies, including glycosyltransferase over
      expression and nucleotide sugar feeding. These multiprong approaches can possibly
      bring us closer toward the goal of maximum and consistent sialylation in
      glycoprotein production using mammalian cells.

PMID- 16432897
TI  - Localization of putative nitrergic neurons in peripheral chemosensory areas and
      the central nervous system of Aplysia californica.
AB  - The distribution of putative nitric oxide synthase (NOS)-containing cells in the
      opisthobranch mollusc Aplysia californica was studied by using NADPH-diaphorase
      (NADPH-d) histochemistry in the CNS and peripheral organs. Chemosensory areas
      (the mouth area, rhinophores, and tentacles) express the most intense staining,
      primarily in the form of peripheral highly packed neuropil regions with a
      glomerular appearance as well as in epithelial sensory-like cells. These
      epithelial NADPH-d-reactive cells were small and had multiple apical ciliated
      processes exposed to the environment. NADPH-d processes were also found in the
      salivary glands, but there was no or very little staining in the buccal mass and
      foot musculature. In the CNS, most NADPH-d reactivity was associated with the
      neuropil of the cerebral ganglia, with the highest density of glomeruli-like
      NADPH-d-reactive neurites in the areas of the termini and around F and C
      clusters. A few NADPH-d-reactive neurons were also found in other central
      ganglia, including paired neurons in the buccal, pedal, and pleural ganglia and a
      few asymmetrical neurons in the abdominal ganglion. The distribution patterns of
      NADPH-d-reactive neurons did not overlap with other known neurotransmitter
      systems. The highly selective NADPH-d labeling revealed here suggests the
      presence of NOS in sensory areas both in the CNS and the peripheral organs of
      Aplysia and implies a role for NO as a modulator of chemosensory processing.

PMID- 16432893
TI  - Molecular determinants of the face map development in the trigeminal brainstem.
AB  - The perception of external sensory information by the brain requires highly
      ordered synaptic connectivity between peripheral sensory neurons and their
      targets in the central nervous system. Since the discovery of the whisker-related
      barrel patterns in the mouse cortex, the trigeminal system has become a favorite
      model for study of how its connectivity and somatotopic maps are established
      during development. The trigeminal brainstem nuclei are the first CNS regions
      where whisker-specific neural patterns are set up by the trigeminal afferents
      that innervate the whiskers. In particular, barrelette patterns in the principal
      sensory nucleus of the trigeminal nerve provide the template for similar patterns
      in the face representation areas of the thalamus and subsequently in the primary
      somatosensory cortex. Here, we describe and review studies of neurotrophins,
      multiple axon guidance molecules, transcription factors, and glutamate receptors
      during early development of trigeminal connections between the whiskers and the
      brainstem that lead to emergence of patterned face maps. Studies from our
      laboratories and others' showed that developing trigeminal ganglion cells and
      their axons depend on a variety of molecular signals that cooperatively direct
      them to proper peripheral and central targets and sculpt their synaptic terminal
      fields into patterns that replicate the organization of the whiskers on the
      muzzle. Similar mechanisms may also be used by trigeminothalamic and
      thalamocortical projections in establishing patterned neural modules upstream
      from the trigeminal brainstem.

PMID- 16432898
TI  - Primary sensory afferent innervation of the developing superficial dorsal horn in
      the South American opossum Monodelphis domestica.
AB  - The development of the primary sensory innervation of the superficial dorsal horn
      (SDH) was studied in postnatal opossums Monodelphis domestica by using DiI
      labelling of primary afferents and with GSA-IB(4) lectin binding and calcitonin
      gene-related peptide (CGRP) immunoreactivity to label primary afferent
      subpopulations. We also compared the timing of SDH innervation in the cervical
      and lumbar regions of the spinal cord. The first primary afferent projections to
      SDH emerge from the most lateral part of the dorsal root entry zone at postnatal
      day 5 and project around the lateral edge of the SDH toward lamina V. Innervation
      of the SDH occurs slowly over the second and third postnatal weeks, with the most
      dorsal aspect becoming populated by mediolaterally oriented varicose fibers
      before the rest of the dorsoventral thickness of the SDH becomes innervated by
      fine branching varicose fibers. Labelling with GSA-IB(4) lectin also labelled
      fibers at the lateral edge of the dorsal horn and SDH at P5, indicating that the
      GSA-IB(4) is expressed on SDH/lamina V primary afferents at the time when they
      are making their projections into the spinal cord. In contrast, CGRP
      immunoreactive afferents were not evident until postnatal day 7, when a few short
      projections into the lateral dorsal horn were observed. These afferents then
      followed a pattern similar to the development of GSA-IB(4) projects but with a
      latency of several days. The adult pattern of labelling by GSA-IB(4) is achieved
      by about postnatal day 20, whereas the adult pattern of CGRP labelling was not
      seen until postnatal day 30. Electron microscopy revealed a few immature synapses
      in the region of the developing SDH at postnatal day 10, and processes considered
      to be precursors of glomerular synapses (and thus of primary afferent origin)
      were first seen at postnatal day 16 and adopted their definitive appearance
      between postnatal days 28 and 55. Although structural and functional development
      of forelimbs of neonatal Monodelphis is more advanced than the hindlimbs, we
      found little evidence of a significant delay in the invasion of the spinal cord
      by primary afferents in cervical and lumbar regions. These observations, together
      with the broadly similar maturational appearance of histological sections of
      rostral and caudal spinal cord, suggest that, unlike the limbs they innervate,
      the spinal regions do not exhibit a large rostrocaudal gradient in their
      maturation.

PMID- 16432899
TI  - Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's
      disease.
AB  - Abnormal subgranular zone (SGZ) neurogenesis is proposed to contribute to
      Alzheimer's disease (AD)-related decreases in hippocampal function. Our goal was
      to examine hippocampal neurogenesis in the PDAPP mouse, a model of AD with age
      dependent accumulation of amyloid-beta(42) (Abeta(42))-containing plaques that is
      well studied with regard to AD therapies. A secondary goal was to determine
      whether altered neurogenesis in the PDAPP mouse is associated with abnormal
      maturation or number of mature cells. A tertiary goal was to provide insight into
      why hippocampal neurogenesis appears to be increased in AD post-mortem tissue and
      decreased in most AD mouse models. We report an age-dependent decrease in SGZ
      proliferation in homozygous PDAPP mice. At 1 year of age, PDAPP mice also had new
      dentate gyrus granule neurons with abnormal maturation and fewer dying cells
      relative to control mice. In contrast to decreased SGZ cell birth, PDAPP mice had
      increased birth of immature neurons in the outer portion of the granule cell
      layer (oGCL), providing insight into why some studies link AD with increased
      neurogenesis. However, these ectopic oGCL cells were still rare compared with SGZ
      proliferating cells, emphasizing that the primary characteristic of PDAPP mice is
      decreased neurogenesis. The decrease in SGZ neurogenesis was not associated with
      an age-dependent loss of dentate granule neurons. The altered neurogenesis in the
      PDAPP mouse may contribute to the age-related cognitive deficits reported in this
      model of AD and may be a useful adjunct target for assessing the impact of AD
      therapies.

PMID- 16432900
TI  - Projections of the nucleus lentiformis mesencephali in pigeons (Columba livia): a
      comparison of the morphology and distribution of neurons with different efferent
      projections.
AB  - The avian nucleus lentiformis mesencephali (LM) is a visual structure involved in
      the optokinetic response. The LM consists of several morphologically distinct
      cell types. In the present study we sought to determine if different cell types
      had differential projections. Using retrograde tracers, we examined the
      morphology and distribution of LM neurons projecting to the vestibulocerebellum
      (VbC), inferior olive (IO), dorsal thalamus, nucleus of the basal optic root
      (nBOR), and midline mesencephalon. From injections into the latter two
      structures, small LM cells were labeled. More were localized to the lateral LM as
      opposed to medial LM. From injections into the dorsal thalamus, small neurons
      were found throughout LM. From injections into the VbC, large multipolar cells
      were found throughout LM. From injections into IO, a strip of medium-sized
      fusiform neurons along the border of the medial and lateral subnuclei was
      labeled. To investigate if neurons project to multiple targets we used
      fluorescent retrograde tracers. After injections into IO and VbC, double-labeled
      neurons were not observed in LM. Likewise, after injections into nBOR and IO,
      double-labeled neurons were not observed. Finally, we processed sections through
      LM for glutamic acid decarboxylase (GAD). Small neurons, mostly in the lateral
      LM, were labeled, suggesting that projections from LM to nBOR and midline
      mesencephalon are GABAergic. We conclude that two efferents of LM, VbC and IO,
      receive input from morphologically distinct neurons: large multipolar and medium
      sized fusiform neurons, respectively. The dorsal thalamus, nBOR, and midline
      mesencephalon receive input from small neurons, some of which are likely
      GABAergic.

PMID- 16432902
TI  - Localization of the urotensin II receptor in the rat central nervous system.
AB  - The vasoactive peptide urotensin II (UII) is primarily expressed in motoneurons
      of the brainstem and spinal cord. Intracerebroventricular injection of UII
      provokes various behavioral, cardiovascular, motor, and endocrine responses in
      the rat, but the distribution of the UII receptor in the central nervous system
      (CNS) has not yet been determined. In the present study, we have investigated the
      localization of UII receptor (GPR14) mRNA and UII binding sites in the rat CNS.
      RT-PCR analysis revealed that the highest density of GPR14 mRNA occurred in the
      pontine nuclei. In situ hybridization histochemistry showed that the GPR14 gene
      is widely expressed in the brain and spinal cord. In particular, a strong
      hybridization signal was observed in the olfactory system, hippocampus, olfactory
      and medial amygdala, hypothalamus, epithalamus, several tegmental nuclei, locus
      coeruleus, pontine nuclei, motor nuclei, nucleus of the solitary tract, dorsal
      motor nucleus of the vagus, inferior olive, cerebellum, and spinal cord.
      Autoradiographic labeling of brain slices with radioiodinated UII showed the
      presence of UII-binding sites in the lateral septum, bed nucleus of the stria
      terminalis, medial amygdaloid nucleus, anteroventral thalamus, anterior pretectal
      nucleus, pedunculopontine tegmental nucleus, pontine nuclei, geniculate nuclei,
      parabigeminal nucleus, dorsal endopiriform nucleus, and cerebellar cortex.
      Intense expression of the GPR14 gene in some hypothalamic nuclei (supraoptic,
      paraventricular, ventromedian, and arcuate nuclei), in limbic structures
      (amygdala and hippocampus), in medullary nuclei (solitary tract, dorsal motor
      nucleus of the vagus), and in motor control regions (cerebral and cerebellar
      cortex, substantia nigra, pontine nuclei) provides the anatomical substrate for
      the central effects of UII on behavioral, cardiovascular, neuroendocrine, and
      motor functions. The occurrence of GPR14 mRNA in cranial and spinal motoneurons
      is consistent with the reported autocrine/paracrine action of UII on motoneurons.

PMID- 16432901
TI  - Embryonic and early postnatal abnormalities contributing to the development of
      hippocampal malformations in a rodent model of dysplasia.
AB  - While there are many recent examples of single gene deletions that lead to
      defects in cortical development, most human cases of cortical disorganization can
      be attributed to a combination of environmental and genetic factors. Elucidating
      the cellular or developmental basis of teratogenic exposures in experimental
      animals is an important approach to understanding how environmental insults at
      particular developmental junctures can lead to complex brain malformations. Rats
      with prenatal exposure to methylazoxymethanol (MAM) reproduce many anatomical
      features seen in epilepsy patients. Previous studies have shown that heterotopic
      clusters of neocortically derived neurons exhibit hyperexcitable firing activity
      and may be a source of heightened seizure susceptibility; however, the events
      that lead to the formation of these abnormal cell clusters is unclear. Here we
      used a panel of molecular markers and birthdating studies to show that in MAM
      exposed rats the abnormal cell clusters (heterotopia) first appear postnatally in
      the hippocampus (P1-2) and that their appearance is preceded by a distinct
      sequence of perturbations in neocortical development: 1) disruption of the radial
      glial scaffolding with premature astroglial differentiation, and 2) thickening of
      the marginal zone with redistribution of Cajal-Retzius neurons to deeper layers.
      These initial events are followed by disruption of the cortical plate and
      appearance of subventricular zone nodules. Finally, we observed the erosion of
      neocortical subventricular zone nodules into the hippocampus around parturition
      followed by migration of nodules to hippocampus. We conclude that prenatal MAM
      exposure disrupts critical developmental processes and prenatal neocortical
      structures, ultimately resulting in neocortical disorganization and hippocampal
      malformations.

PMID- 16432903
TI  - Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is
      mediated by lipoprotein receptors for Reelin and Disabled 1.
AB  - Reelin is a positional signal for the lamination of the dentate gyrus. In the
      reeler mutant lacking Reelin, granule cells are scattered all over the dentate
      gyrus. We have recently shown that the reeler phenotype of the dentate gyrus can
      be rescued in vitro by coculturing reeler hippocampal slices with slices from
      wild-type hippocampus. Here we studied whether Reelin from other brain regions
      can similarly induce this rescue effect and whether it is mediated via the Reelin
      receptors apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein
      receptor (VLDLR). We found that coculturing reeler hippocampal slices with slices
      from wild-type olfactory bulb, cerebellum, and neocortex rescued the reeler
      phenotype as seen before with hippocampal slices, provided that the Reelin
      synthesizing cells of these regions were placed near the marginal zone of the
      reeler hippocampal slice. However, coculturing wild-type hippocampal slices with
      hippocampal slices from mutants deficient in ApoER2 and VLDLR did not rescue the
      reeler-like phenotype in these cultures. Similarly, no rescue of the reeler-like
      phenotype was observed in slices from mutants lacking Disabled 1 (Dab1), an
      adapter protein downstream of Reelin receptors. Conversely, reeler hippocampal
      slices were rescued by coculturing them with slices from Dab1(-/-) mutants or
      ApoER2(-/-)/VLDLR(-/-) mice. These findings show that Reelin from other brain
      regions can substitute for the loss of hippocampal Reelin and that rescue of the
      reeler phenotype observed in our coculture studies is mediated via lipoprotein
      receptors for Reelin and Dab1.

PMID- 16432905
TI  - Convergence of spinal trigeminal and cochlear nucleus projections in the inferior
      colliculus of the guinea pig.
AB  - In addition to ascending auditory inputs, the external cortex of the inferior
      colliculus (ICX) receives prominent somatosensory inputs. To elucidate the extent
      of interaction between auditory and somatosensory representations at the level of
      IC, we explored the dual projections from the cochlear nucleus (CN) and the
      spinal trigeminal nucleus (Sp5) to the inferior colliculus (IC) in the guinea
      pig, using both retrograde and anterograde tracing techniques. Injections of
      retrograde tracers into ICX resulted in cell-labeling primarily in the
      contralateral DCN and pars interpolaris and caudalis of Sp5. Labeled cells in DCN
      were either fusiform or multipolar cells, whereas those in Sp5 varied in size and
      shape. Injections of anterograde tracers into either CN or Sp5 resulted in
      terminal labeling in ICX primarily on the contralateral side. Most projection
      fibers from Sp5 terminated in a laminar pattern from ventromedial to dorsolateral
      within the ventrolateral ICX, the ventral border of IC, and the ventromedial edge
      of IC (collectively termed "the ventrolateral border region of IC," ICXV). Less
      dense anterograde labeling was observed in lateral and rostral ICX. Injecting
      different tracers into both Sp5 and CN confirmed the overlapping areas of
      convergent projections from Sp5 and CN in IC: The most intense dual labeling was
      seen in the ICXV, and less intense dual labeling was also observed in the rostral
      part of ICX. This convergence of projection fibers from CN and Sp5 provides an
      anatomical substrate for multimodal integration in the IC.

PMID- 16432906
TI  - Histological and electrophysiological properties of crypt cells from the
      olfactory epithelium of the marine teleost Trachurus symmetricus.
AB  - Crypt cells from the olfactory epithelium of the Pacific jack mackerel Trachurus
      symmetricus were characterized by light and electron microscopy and analyzed in
      dissociation with the patch-clamp technique in its cell-attached, perforated
      patch and normal whole-cell mode. Isolated crypt cells remained united with their
      supporting cells, and both were electrically coupled through gap junctions. Under
      voltage-clamp, depolarizing voltage steps triggered a transient sodium current, a
      sustained calcium current, and two types of potassium currents with fast and slow
      inactivation kinetics. No calcium-dependent potassium current could be observed.
      The sodium current was blocked by saxitoxin, the calcium current by cobalt and
      furnidipine, and the potassium currents by tetraethylammonium chloride. In the
      cell-attached configuration, crypt cells displayed spontaneous spike activity and
      responded to amino acid solutions with dose-dependent excitation, followed by a
      period of spike inhibition. These first recordings of individual crypt cells
      provide the basis for future studies of their odorant specificity, transduction
      mechanism, and overall function in the fish olfactory epithelium.

PMID- 16432907
TI  - Ontogeny of the projections from the anteroventral periventricular nucleus of the
      hypothalamus in the female rat.
AB  - Neurons in the anteroventral periventricular nucleus of the hypothalamus (AVPV)
      mediate a variety of autonomic functions. In adults they primarily innervate
      neuroendocrine nuclei in the periventricular zone of the hypothalamus, including
      the paraventricular and arcuate nuclei (PVH, ARH). Ascending projections from the
      AVPV also provide inputs to the ventrolateral septum (LSv) and the principal
      division of the bed nuclei of the stria terminalis (BSTp). Consistent with a role
      in regulating preovulatory luteinizing hormone secretion, rostral projections
      from the AVPV contact gonadotropin-releasing hormone (GnRH) neurons surrounding
      the vascular organ of the lamina terminalis (OVLT). To study the development of
      these pathways, we placed implants of the lipophilic tracers DiI and CMDiI into
      the AVPV of female rats ranging in age from embryonic day 19 (E19) through
      adulthood. The earliest projections targeted a population of GnRH neurons, with
      apparent contacts from labeled fibers observed as early as E19. These connections
      appeared to be fully developed before birth, as similar numbers of appositions
      from AVPV projections onto the GnRH-immunoreactive cells were observed at all
      ages examined. Caudal projections were delayed relative to projections to the
      OVLT. Labeled AVPV fibers reached the PVH during the first postnatal week, and
      fibers targeting the BSTp and LSv were not observed until the second and third
      postnatal weeks, respectively. Labeled AVPV fibers were not seen in the ARH of
      animals at any age. Our results demonstrate that projections from the AVPV
      develop with both spatial and temporal specificity, innervating each target with
      a unique developmental profile.

PMID- 16432904
TI  - Cytoarchitectonic identification and probabilistic mapping of two distinct areas
      within the anterior ventral bank of the human intraparietal sulcus.
AB  - Anatomical studies in the macaque cortex and functional imaging studies in humans
      have demonstrated the existence of different cortical areas within the
      intraparietal sulcus (IPS). Such functional segregation, however, does not
      correlate with presently available architectonic maps of the human brain. This is
      particularly true for the classical Brodmann map, which is still widely used as
      an anatomical reference in functional imaging studies. The aim of this
      cytoarchitectonic mapping study was to use previously defined algorithms to
      determine whether consistent regions and borders can be found within the cortex
      of the anterior IPS in a population of 10 post-mortem human brains. Two areas,
      the human intraparietal area 1 (hIP1) and the human intraparietal area 2 (hIP2),
      were delineated in serial histological sections of the anterior, lateral bank of
      the human IPS. The region hIP1 is located posterior and medial to hIP2, and the
      former is always within the depths of the IPS. The latter, on the other hand,
      sometimes reaches the free surface of the superior parietal lobule. The
      delineations were registered to standard reference space, and probabilistic maps
      were calculated, thereby quantifying the intersubject variability in location and
      extent of both areas. In the future, they can be a tool for analyzing structure
      function relationships and a basis for determining degrees of homology in the IPS
      among anthropoid primates. We conclude that the human IPS has a more finely
      grained parcellation than shown in Brodmann's map.

PMID- 16432908
TI  - Signal amplification by allosteric catalysis.
AB  - In this article we unify a series of recent studies on bio- and chemosensors
      under a single signaling strategy: signal amplification by allosteric catalysis
      (SAAC). The SAAC strategy mimics biological signal transduction processes, where
      molecular recognition between an external signal and a protein receptor is
      allosterically transduced into catalytically amplified chemical information
      (usually second messengers). Several recent biosensing and chemosensing studies
      apply this nature-inspired strategy by using engineered allosteric enzymes,
      ribozymes, or regulatable organic catalysts. The factors pertinent to achieving
      high sensitivity and specificity in SAAC strategies are analyzed. The authors
      believe that these early studies from a variety of research groups have opened up
      a new venue for the development of sensing technologies where molecular
      recognition and catalysis can be coupled for practical purposes.

PMID- 16432910
TI  - Task-specific ionic liquids bearing 2-hydroxybenzylamine units: synthesis and
      americium-extraction studies.
AB  - The synthesis of two task-specific ionic liquids (TSILs) bearing 2
      hydroxybenzylamine entities is described. These compounds are based on an
      imidazolium substructure onto which one hydrobenzylamine-complexing moiety is
      grafted. We have demonstrated that, whether pure or diluted, TSIL is able to
      extract americium ions. Furthermore, recovery of americium from the IL phase into
      a receiving phase can be achieved under acidic conditions. A possible mechanism
      for the metal-ion partitioning is presented, in which the extraction system is
      driven by an ion-exchange mechanism.

PMID- 16432909
TI  - A central strategy for converting natural products into fluorescent probes.

PMID- 16432911
TI  - In situ spectroelectrochemical studies on ladder-type oligomers in solution and
      the solid state.
AB  - A series of thermally stable fluoranthenopyracylene oligomers with extended pi
      conjugation were studied by in situ ESR-UV/Vis/NIR spectroelectrochemistry with
      respect to their application in devices such as organic light-emitting diodes and
      field-effect transistors. The oligomers are both soluble in o-dichlorobenzene and
      form thin films by evaporation in the temperature range of 300-500 degrees C in
      vacuum. Their electrochemical behavior was studied in reduction (n doping) and
      oxidation (p doping) under standard voltammetric and thin-layer conditions. The
      HOMO and LUMO energies and the band gaps of all compounds under study were
      estimated from both electrochemical and UV/Vis/NIR spectroscopic data. The
      fluorene-type oligomers A(2)-A(6) and B(2) bearing flexible alkyl chains exhibit
      both reversible multistep reductions and oxidations. The spectroelectrochemistry
      indicates substantial differences in delocalization of the positive and negative
      charges in these ladder-type oligomers. The formation of doubly charged sigma
      dimers was observed for the first time for both the radical anion and radical
      cation of the same molecule (B(1)). The redox behavior of the oligomers was
      studied in the solid state and in solution.

PMID- 16432912
TI  - Ruthenium-catalyzed asymmetric epoxidation of olefins using H2O2, part II:
      catalytic activities and mechanism.
AB  - Asymmetric epoxidation of olefins with 30 % H2O2 in the presence of
      [Ru(pybox)(pydic)] 1 and [Ru(pyboxazine)(pydic)] 2 has been studied in detail
      (pybox = pyridine-2,6-bisoxazoline, pyboxazine = pyridine-2,6-bisoxazine, pydic =
      2,6-pyridinedicarboxylate). 35 Ruthenium complexes with sterically and
      electronically different substituents have been tested in environmentally benign
      epoxidation reactions. Mono-, 1,1-di-, cis- and trans-1,2-di-, tri-, and tetra
      substituted aromatic olefins with versatile functional groups can be epoxidized
      with this type of catalyst in good to excellent yields (up to 100 %) with
      moderate to good enantioselectivies (up to 84 % ee). Additive and solvent effects
      as well as the relative rate of reaction with different catalysts have been
      established. It is shown that the presence of weak organic acids or an electron
      withdrawing group on the catalyst increases the reactivity. New insights on the
      reaction intermediates and reaction pathway of the ruthenium-catalyzed
      epoxidation are proposed on the basis of density functional theory calculation
      and experiments.

PMID- 16432913
TI  - Stereoselective binding of human serum albumin.
AB  - Stereoselectivity in binding can have a significant effect on the drug
      disposition such as first-pass metabolism, metabolic clearance, renal clearance,
      and protein and tissue binding. Human serum albumin (HSA) is able to
      stereoselectively bind a great number of various endogenous and exogenous
      compounds. Various experimental data suggested that the two major drug-binding
      cavities, namely, site I and site II, do not seem to be the stereoselective
      binding sites of HSA. Stereoselective binding of HSA under disease conditions
      such as renal and hepatic diseases was found to be enhanced. In addition, site-to
      site displacement of a site II-specific drug by another site II-specific drug was
      found to be stereoselective, too. Endogenous compounds such as long-chain fatty
      acids and uremic toxins are likely to cause combined direct and cascade effects
      that contribute to the preferential binding of a particular drug enantiomer.
      Taking together the findings of other studies, it is highly possible that the
      stereoselective binding site exists at the interface of the subdomains.

PMID- 16432914
TI  - Roles of phenylalanine at position 120 and glutamic acid at position 222 in the
      oxidation of chiral substrates by cytochrome P450 2D6.
AB  - The roles of Phe-120 and Glu-222 in the oxidation of chiral substrates bunitrolol
      (BTL) and bufuralol (BF) by CYP2D6 are discussed. Wild-type CYP2D6 (CYP2D6-WT)
      oxidized BTL to 4-hydroxybunitrolol (4-OH-BTL) with substrate enantioselectivity
      of (R)-(+)-BTL > (S)-(-)-BTL. The same enzyme converted BF into 1''
      hydroxybufuralol with substrate enantioselectivity of (R)-BF >> (S)-BF and
      metabolite diastereoselectivity of (1''R)-OH < (1''S)-OH. The substitution of Phe
      120 by alanine markedly increased the apparent K(m) and V(max) values for
      enantiomeric BTL 4-hydroxylation by CYP2D6. In contrast, the same substitution
      caused an increase only in V(max) values of (S)-BF 1''-hydroxylation without
      changing apparent K(m) values, while kinetic parameters (K(m) and V(max) values)
      for (R)-BF 1''-hydroxylation remained unchanged. Furthermore, the substitution of
      Glu-222 as well as Glu-216 by alanine remarkably decreased both the apparent K(m)
      and V(max) values without changing substrate enantioselectivity or metabolite
      diastereoselectivity. A computer-assisted simulation study using energy
      minimization and molecular dynamics techniques indicated that the hydrophobic
      interaction of an aromatic moiety of the substrate with Phe-120 and the ionic
      interaction of a basic nitrogen atom of the substrate with Glu-222 in combination
      with Glu-216 play important roles in the binding of BF and BTL by CYP2D6 and the
      orientation of these substrates in the active-site cavity. This modeling yielded
      a convincing explanation for the reversal of substrate enantioselectivity in BTL
      4-hydroxylation between CYP2D6-WT and CYP2D6-V374M having methionine in place of
      Val-374, which supports the validity of this modeling.

PMID- 16432915
TI  - Asymmetric [2+2] photocycloaddition of cycloalkenone-cyclodextrin complexes to
      ethylene.
AB  - The enantioselective [2+2] photocycloaddition of cycloalkenone-cyclodextrin
      complexes to ethylene was examined. Photoreaction of alpha-, beta-, and gamma
      cyclodextrin complexes of various cyclohexenonecarboxylates and
      cyclopentenonecarboxylates in the presence of ethylene in the solid state or in
      aqueous suspension gave corresponding photocycloadducts with chiral induction.

PMID- 16432916
TI  - Preparation of enantiopure Wieland-Miescher ketone and derivatives by the
      MalphaNP acid method: substituent effect on the HPLC separation.
AB  - Enantiopure Wieland-Miescher ketone (4, W-M ketone) and derivatives were prepared
      by the enantioresolution with 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP
      acid 1). Various racemic derivatives of 4 were esterified with acid (S)-(+)-1
      yielding diastereomeric MalphaNP esters, which were separated by HPLC on silica
      gel. It was clarified that the HPLC separation of diastereomers depended on the
      substituent of the derivatives, leading to the working hypothesis that MalphaNP
      acid esters of alcohols with less polar and more bulky aliphatic substituents are
      more effectively separated. The best separation was obtained in the case of tert
      butyldimethylsilyl (TBDMS) ether derivative (12a/12b): separation factor
      alpha=1.80, and resolution factor, Rs=1.30. The (1)H NMR spectra of separated
      MalphaNP esters showed anomalously large magnetic anisotropy effects, from which
      their absolute configurations were determined. Solvolysis or reduction of the
      separated MalphaNP esters yielded alcohols, which were converted to enantiopure W
      M ketones 4. The results thus provided another route for preparation of
      enantiopure ketones (8aR)-(-)-4 and (8aS)-(+)-4.

PMID- 16432918
TI  - Preferential enrichment: significant influence of minor molecular modification on
      the mode of polymorphic transition during crystallization.
AB  - The relationship between the molecular structure and the occurrence of
      Preferential Enrichment, an unusually symmetry-breaking enantiomeric resolution
      phenomenon observed upon simple recrystallization of a certain kind of racemic
      crystals from organic solvents, has been investigated with respect to a new
      series of racemic ammonium sulfonate compounds. Racemic [2-[4-(3-ethoxy-2
      hydroxypropoxy)phenylcarbamoyl]ethyl]trimethylammonium p-iodobenzenesulfonate
      [(+/-)-1a] can show preferential enrichment by simple recrystallization from
      EtOH, whereas its terminal methoxy and propoxy derivatives [(+/-)-1b and (+/-)
      1c] are unable to do so. The influence of such a minor molecular modification on
      Preferential Enrichment has been rationalized in terms of the change of the mode
      of polymorphic transition during crystallization, which has been confirmed by in
      situ ATR-FTIR (ReactIR) spectroscopy in solution and in the solid state and by X
      ray crystallographic analysis of their single crystals.

PMID- 16432919
TI  - Effect of phosphatidylcholine vesicle size on chirality induction and chiral
      discrimination.
AB  - The effect of the size of phosphatidylcholine (PC) vesicles on the induction of
      chirality and chiral discrimination was examined. Three kinds of vesicles formed
      with l-dimyristoyl, l-dipalmitoyl, or egg yolk PCs induced circular dichroisms
      (CDs) with the sign and intensity of the Cotton effect different from those of
      monomeric PCs. The CD intensity of the vesicles increased with a decrease in the
      vesicle size. Furthermore, the helicity of heterohelicene derivatives in a rapid
      equilibrium between right-handed (P) and left-handed (M) enantiomers was biased
      toward the M enantiomer side in l-PC vesicles, implying chiral discrimination by
      the vesicles. The extent of the bias toward the M enantiomer increased with an
      increase in vesicle size. Both the chirality induction and chiral discrimination
      were enhanced in a low-fluidity gel phase in comparison with those in a high
      fluidity liquid-crystalline phase for every kind of vesicle of every size
      examined.

PMID- 16432920
TI  - Development of vacuum-ultraviolet circular dichroism measurement system using a
      polarizing undulator.
AB  - We have developed an improved circular dichroism (CD) and linear dichroism (LD)
      simultaneous measurement system for the vacuum ultraviolet (VUV) region by
      polarization modulation techniques using a four-period Onuki-type crossed
      undulator as a polarized light source. The system has been constructed at the VUV
      beamline BL-5 in the electron storage ring TERAS, at AIST. Our improvements, in
      particular the adoption of an optical chopper as the detection method of incident
      light, have resulted in a flat baseline and a consequent simplification of the
      Mueller matrix calculation for our optical system. Based on the Mueller matrix
      calculation, we have successfully measured real VUV-CD and LD spectra of leucine
      films for wavelengths down to 160 nm with absolute optical constants. The
      obtained spectra show good consistency with spectra measured by conventional
      methods.

PMID- 16432921
TI  - A novel spectroscopic probe for molecular chirality.
AB  - Recent advances in developing sum frequency generation (SFG) as a novel
      spectroscopic probe for molecular chirality are reviewed. The basic principle
      underlying the technique is briefly described, in comparison with circular
      dichroism (CD). The significantly better sensitivity of the technique than CD is
      pointed out, and the reason is discussed. Bi-naphthol (BN) and amino acids are
      used as representatives for two different types of chiral molecules; the measured
      chirality in their electronic transitions can be understood by two different
      molecular models, respectively, that are extensions of models developed earlier
      for CD. Optically active or chiral SFG from vibrational transitions are weaker,
      but with the help of electronic-vibrational double resonance, the vibrational
      spectrum of a monolayer of BN has been obtained. Generally, optically active SFG
      is sufficiently sensitive to be employed to probe in-situ chirality of chiral
      monolayers and thin films.

PMID- 16432922
TI  - Absolute configuration determination of donor-acceptor [2.2]paracyclophanes by
      comparison of theoretical and experimental vibrational circular dichroism
      spectra.
AB  - Vibrational circular dichroism (VCD) spectra were obtained for the assignments of
      the absolute configurations of diastereomeric 4,7-bis(methoxycarbonyl)-12,15
      dimethoxy-[2.2]paracyclophanes (1 and 2), and density functional theory (DFT)
      calculations were performed at the B3LYP/6-31G(d) level for all possible
      conformations of both 1 and 2 to give the theoretical VCD spectra. Comparisons of
      the experimental and theoretical VCD spectra obtained unambiguously established
      the absolute configurations of the dextrorotatory (+)-enantiomers as
      (4S(p);12S(p))-1 and (4S(p);12R(p))-2, respectively.

PMID- 16432923
TI  - Characterization of poly[(R)-3-hydroxybutyrate-co-epsilon-caprolactone]
      copolymers by matrix-assisted laser desorption/ionization time-of-flight and
      electrospray ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) of narrowly dispersed molecular weight gel permeation
      chromatography (GPC) fractions was used to characterize random and microblock
      poly[(R)-3-hydroxybutyrate-co-epsilon-caprolactone] [P(HB-co-CL)] copolymers
      obtained via the acid-catalyzed transesterification of the corresponding
      homopolymers, poly([(R)-3-hydroxybutyrate] (PHB) and poly(epsilon-caprolactone)
      (PCL). High-quality mass spectra were obtained, which made it possible to
      establish the nature of the polymer end groups. Besides the carboxylic
      termination, two other moieties were found: alcoholic and tosyl end groups. MALDI
      mass spectra of CL-rich samples possessed mostly tosyl end groups, while HB-rich
      samples possessed mostly alcoholic end groups, showing that the tosyl moiety is
      linked prevalently to CL terminal units. The higher resolution of electrospray
      ionization (ESI) mass spectra of lower molecular weight GPC fractions permitted
      the identification of the different oligomer species hypothesized in the
      assignment of the corresponding MALDI mass spectra. Partial methanolysis of these
      copolymers was explored as a method of producing mixed HB-CL oligomers to be
      utilized as new synthons, possessing a minor number of chiral centers from those
      obtained from hydrolysis of biotechnologically synthesized
      poly(hydroxyalkanoates) (PHAs).

PMID- 16432924
TI  - The other side: failure in fair and balanced reporting.

PMID- 16432925
TI  - Molecular and cellular targets in tissue remodelling.

PMID- 16432926
TI  - Justices reject U.S. bid to block assisted suicide; Court, 6-3, says attorney
      general was wrong in Oregon case.

PMID- 16432927
TI  - Are you my sperm donor? Few clinics will say.

PMID- 16432928
TI  - A challenge to the Japanese proposals to improve the draft recommendations of the
      ICRP.

PMID- 16432930
TI  - Teaching in depth.

PMID- 16432929
TI  - Baverstock and Ball article.

PMID- 16432931
TI  - Prevention. Activists: AIDS programs undermined by Congress.

PMID- 16432932
TI  - Activists lift boycott of Abbott Laboratories.

PMID- 16432934
TI  - Assault. HIV-positive man's failure-to-protect suit survives dismissal.

PMID- 16432933
TI  - Disclosure. Workplace discrimination case survives dismissal motion.

PMID- 16432935
TI  - Exposure. Woman's suit fails after being infected by HIV in lab.

PMID- 16432936
TI  - Lambda files appeal in government discrimination case.

PMID- 16432937
TI  - HIV and gender. U.N.: gender affects HIV transmission, intervention efforts.

PMID- 16432938
TI  - [Relation between tumor necrosis factor-alpha and vascular endothelium growth
      factor with etiology of high altitude heart disease].

PMID- 16432939
TI  - [CT-guided transthoracic puncture of peripheral pulmonary nodules using a special
      bioptic needle].

PMID- 16432940
TI  - A set of Roman medical instruments from Italy.

PMID- 16432941
TI  - Tonsor humanus: razor and toilet-knife in antiquity.

PMID- 16432942
TI  - Population change in Roman London.

PMID- 16432943
TI  - The legionary hospital at Inchtuthil.

PMID- 16432944
TI  - Health care in the Roman North.

PMID- 16432945
TI  - Human remains from the North Gate, Silchester: an 'early' and a 'late'
      radiocarbon date from the city.

PMID- 16432946
TI  - [Guidelines for the diagnosis and treatment of chronic heart failure: executive
      summary (update 2005)].

PMID- 16432947
TI  - ["Evromedlab-2005" - the 16th Congress of Laboratory Specialists from Europe].

PMID- 16432948
TI  - Chromosomal instability, aneuploidy, and gene mutations in human sporadic
      colorectal adenomas.

PMID- 16432950
TI  - Bibliography. Current world literature. Coronary artery disease.

PMID- 16432951
TI  - Bibliography. Current world literature. Ischemic heart disease.

PMID- 16432952
TI  - Abstracts of scientific papers presented at the 9th Annual Meeting of the
      Biofeedback Foundation of Europe.

PMID- 16432954
TI  - Commentary: amphiphiles and their aggregates in basic and applied science. A post
      conference thought on nomenclature.

PMID- 16432953
TI  - A single-dose placebo-controlled study of AMG 162, a fully human monoclonal
      antibody to RANKL, in postmenopausal women. 2004.

PMID- 16432955
TI  - Summarizing a disaster, by the numbers.

PMID- 16432956
TI  - Comments on grant dollars for veterinary schools.

PMID- 16432957
TI  - Questions common use of claw to describe hoof.

PMID- 16432958
TI  - Do the victims of free-roaming cats have rights?

PMID- 16432959
TI  - Unexpected gift keeps on giving.

PMID- 16432960
TI  - Thoughts on task force report on housing for pregnant sows.

PMID- 16432961
TI  - Thoughts on task force report on housing for pregnant sows.

PMID- 16432962
TI  - [Buccal mucosa for urethral reconstruction in hypospadias repair].

PMID- 16432963
TI  - [High-frequency ventilation in the treatment of sleep apnea syndrome in diabetes
      mellitus].

PMID- 16432964
TI  - "Dental Research in Primary Care." Papers Presented at the IADR Pan-European
      Federation Meeting. Cardiff, Wales, UK, September 2002.

PMID- 16432965
TI  - [Effects of aminophylline on the secretion of thyroid hormones and the changes of
      heart rate and rhythm].

PMID- 16432966
TI  - [Hydrogen peroxide with ultrasonographic guide in the diagnosis of female
      infertility caused by fallopian tube obstruction].

PMID- 16432967
TI  - [Cumulative incidence and distribution of congenital heart diseases in newborns
      in Beirut and its southern suburb (1999-2002)].
AB  - OBJECTIVES: To analyze the incidence and distribution of congenital heart
      diseases (CHD) in Beirut and its southern suburb. MATERIALS AND METHODS: 27834
      consecutive live births were examined (13894 boys and 13940 girls), between 1999
      and 2002, in six hospital centers in Beirut and its southern suburb. CHD were
      analyzed according to age at diagnosis, sex and severity of malformation. The
      rate of consanguinity among the parents of the studied population was studied.
      RESULTS: 249 CHD were detected (cumulative incidence: 8.95 per thousand), of whom
      81.5% while still in the neonatal/antenatal period. Ventricular septal defect was
      the commonest (38.2%), followed by pulmonary stenosis (9.6%) and atrial septal
      defect (7.6%); 23.3% of CHD were cyanotic. The frequency of double outlet right
      ventricle, pulmonary atresia with VSD, aortic stenosis, and atrio-ventricular
      canal were higher than reported in the international literature, but comparable
      to reports from the Arab Gulf countries (except aortic stenosis). In the affected
      children, the rate of consanguinity (1st degree) among their parents was 17.7%.
      CONCLUSION: The incidence and distribution of CHD in the studied area is similar
      to that reported in the literature, but differences were observed concerning some
      types of malformations. We believe that certain measures are needed to improve
      the detection of CHD that were not detected early in life. Such measures include:
      the administration of oxymetry tests before discharge from nursery, bringing the
      first neonatal examination post-discharge down to age 5 to 15 days of life,
      offering free diagnostic care for children of poor population, and the
      participation of the physicians in Lebanon to a national registry for cardiac
      diseases in children.

PMID- 16432968
TI  - Cisplatin and vinorelbine (PVn) for the treatment of advanced breast cancer: 10
      years of experience.
AB  - Breast cancer is the most common malignancy in women throughout the world. It is
      the leading cause of cancer death of women aged > 50 years. Cisplatin and
      vinorelbine are active as single agents in advanced breast cancer but their
      combination was not studied before. We conducted three phase II trials using this
      combination in advanced breast cancer. Hereby, we describe our experience over a
      10-year period at the American University of Beirut using this combination in
      metastatic disease as 1st and 2nd line therapy as well as in the neoadjuvant
      setting in patients with locally advanced disease. Our data will be compared with
      other groups using the same regimen for the management of advanced breast
      carcinoma.

PMID- 16432969
TI  - Diagnosis and management of tracheal stenosis.
AB  - Tracheal stenosis is defined as cicatricial narrowing of the endotracheal lumen.
      Endotracheal manipulation remains to be the most common etiology followed by
      inflammatory and collagen vascular diseases. Predisposing factors include host
      systemic conditions such as gastroesophageal reflux and tube characteristics
      mainly the size and composition of the tube. The clinical picture may be
      misleading and ranges from mild decrease in exercise tolerance to severe
      respiratory distress. The patient is usually investigated radiologically followed
      by flexible or rigid laryngoscopy and bronchoscopy. Computerized tomography is
      used more often than magnetic resonance imaging and correlates well with the
      endoscopic findings. The cervical portion of the trachea is usually involved with
      marked narrowing varying in length and diameter. The treatment includes
      endoscopic repair, laryngotracheal reconstruction or segmental resection with end
      to end anastomosis. A total of thirteen cases of adult tracheal stenosis,
      diagnosed and managed at the American University of Beirut between 1996 and 2003
      were reviewed. The clinical presentation, etiology, diagnostic and therapeutic
      approaches are presented in this study.

PMID- 16432970
TI  - Medialization laryngoplasty for the treatment of unilateral vocal cord paralysis:
      a perceptual, acoustic and stroboscopic evaluation.
AB  - Vocal cord paralysis remains a frustrating condition. The etiology can be
      subdivided roughly into surgically induced, neoplastic and idiopathic paralysis.
      In the surgical group, thyroidectomy is the most common cause. In unilateral
      vocal cord paralysis most patients suffer from a change in voice quality
      described as hoarseness or breathiness with or without aspiration and dysphagia.
      Laryngeal examination usually reveals the paralyzed cord shorter than the normal
      side and mostly in the paramedian position. Endostroboscopic examination shows
      invariably incomplete closure of the vocal cords with marked decrease in the
      mucosal waves of the folds during phonation. Several procedures for vocal cord
      medialization such as endoscopic injection of different materials, medialization
      thyroplasty, arytenoids adduction and re-innervation procedures have been
      described in the literature. Laryngoplastic phonosurgery for surgical
      rehabilitation of the paralyzed vocal cord has markedly evolved over the last few
      decades. This is a review of patients with unilateral vocal cord paralysis
      treated by medialization laryngoplasty at the American University of Beirut,
      Department of Otolaryngology Head and Neck Surgery, between 1994 and 2003. The
      etiology of the paralysis, symptomatology, endostroboscopic and acoustic findings
      will be presented together with a description of the surgical technique.

PMID- 16432971
TI  - Prevalence and determinants of water pipe or narghile use among students in
      Beirut's southern suburbs.
AB  - OBJECTIVES: Measuring the prevalence and determinants of narghile smoking among
      teenagers in schools in the southern suburbs (Dahia) of Beirut, Lebanon. METHODS:
      A simplified questionnaire was self-completed by intermediate and secondary
      students selected from private and public schools in Dahia the year 2001-2002.
      Variables obtained included details on narghile and cigarette smoking, socio
      demographic characteristics of the student and his/her family, friendship
      networks, and beliefs regarding health. RESULTS: A total of 1461 students
      completed the questionnaire, of which 24% admitted regularly (> once/week)
      smoking the narghile and 14.4% occasionally, with a male predominance. The
      initiation was at about 13.6 yrs of age, but it varied from as low as 5 to 18
      yrs. At least 28% of first narghile trial took place with a member of the
      immediate family, even though 58.2% initiated with a user friend. The monthly
      cost of using narghile did not exceed 7 USD for about half of narghile users in
      that area. CONCLUSIONS: Narghile use is a behavior gaining in importance in
      Lebanon in general, and in the Dahia area in particular. Its initiation among
      adolescents means that the probability of addiction is higher and the adverse
      health consequences are potentially more severe. It requires immediate
      interventional procedures including the launching of a campaign of national
      awareness for which hard data, such as those provided by this study, will be
      needed.

PMID- 16432973
TI  - Dyslipidemia and the risk of end stage renal disease.

PMID- 16432972
TI  - [Human brucellosis in Lebanon. Clinical features and therapeutic responses in 88
      patients].
AB  - OBJECTIVES: Present clinical features of brucellosis in Lebanon. METHODS: Eighty
      eight patients were seen at Hotel-Dieu de France Hospital of Beirut between 1994
      and 2002. Diagnostic criteria were brucellar agglutinins at a titer; 1/160 with
      symptoms suggestive of brucellosis in the absence of other diagnosis and a
      therapeutic response. RESULTS: Out of the 88 hospitalized patients, 11 pediatric
      cases are noted. The disease is acute in 58 (66%), subacute in 28 (32%) and
      chronic in 2. The main presenting symptoms are fever, sweating, easy fatigability
      and diffuse aches. Osteoarticular involvement is the most prevalent complication
      (28%) and spondylitis is seen in 44% of these cases. Meningoencephalitis is the
      most frequent neurological manifestation. Among the haematological tests,
      relative lymphocytosis is significantly more frequent in children than adults
      (73% vs 19% ; p < 0,001) and in the acute form than the subacute (36% vs 7%; p <
      0,001) whereas leucocytosis is more frequent in the subacute form (21% vs 7%; p <
      0,01). CONCLUSION: Brucellosis is still an endemic disease in Lebanon and should
      be systematically evoked in the case of prolonged fever, articular and
      neurological manifestations.

PMID- 16432974
TI  - Extracorporeal treatment in Gram negative sepsis how far have we gone?

PMID- 16432975
TI  - [Utility of endoscopic ultrasonography on localization of insulinomas. Case
      report and review of the literature].
AB  - Insulinoma is the most common endocrine tumors of the pancreas. The diagnosis is
      suspected by clinical symptoms and confirmed by biologic tests. Because the
      majority of insulinomas have a small size, the real problem is the localization
      of these tumors. The non invasive radiologic exams (US, CT Scan, angiography or
      RMI) are not sensitive for the topographic localization of insulinomas. The
      invasive exams like per operative US and palpation of the parenchyma or dosage of
      insulin by transhepatic catheterization of portal vein or in hepatic vein after
      intrarterial stimulation are very sensitive. The only noninvasive preoperative
      exam with high sensitivity to localize insulinomas is endoscopic ultrasonography
      (EUS). We report a case of insulinoma localized by EUS with review of the
      literature.

PMID- 16432976
TI  - Intrathoracic transverse colon and small bowel infarction in a patient with
      traumatic diaphragmatic hernia. Case report and review of the literature.
AB  - OBJECTIVE: Herniation of abdominal contents through the diaphragm has been
      described for a variety of diaphragmatic defects and may be secondary to
      diaphragmatic injury, either traumatic or iatrogenic. The sequelae of
      diaphragmatic hernia include intestinal obstruction, strangulation, gangrene and,
      eventually, perforation. The aim of this study was to report a case of
      intrathoracic infarction of transverse colon and two meters of small bowel in a
      patient with traumatic diaphragmatic hernia. PATIENT: Young man with past history
      of blunt abdominal trauma presented abdominal pain with dyspnea. An exploratory
      laparotomy was performed. The esophageal hiatus was normal but a 4.5 cm rent was
      discovered in the posterior leaf of the left hemidiaphragm. Passing through the
      defect was the transverse colon and a proximal small bowel. The herniated
      transverse colon and jejunum were massively dilated with evidence of infarction.
      Transverse colectomy and resection of two meters of jejunum with direct
      anastomosis were performed. Following bowel removal, diaphragm was directly
      repaired without graft. Finally, a chest tube was placed in the left hemithorax.
      RESULTS: Postoperative course was uneventful and he recovered without
      complications. He was discharged from hospital 10 days after surgery. CONCLUSION:
      Surgeons, internists and emergency medicine personnel should be aware of the
      possibility of diaphragmatic hernia in patients with a known history of abdominal
      trauma. Though uncommon, strangulation of colon and small bowel through a rent in
      diaphragm should be considered when there is radiologic evidence of herniation.

PMID- 16432977
TI  - [Cardiac pacing in children with severe form of breath-holding spells, an
      exceptional treatment. A case report].
AB  - Breath-holding spells (BHS) are frequent and benign in children. Medical
      treatment is rarely needed but exceptionally severe forms require the
      implantation of a pacemaker. We describe here the case of an 18-month-old girl
      who presented to our department with severe episodes of BHS associated with loss
      of consciousness. This child necessitated the insertion of a pacemaker, which
      resolved her BHS.

PMID- 16432979
TI  - Evaluation of lower urinary tract symptoms (LUTS).
AB  - LUTS often represent serious underlying diseases with morbid consequences.
      Awareness of these clinical entities is mandatory to arrive at differential
      diagnosis in fast and least expensive methods. Thus initiate the appropriate
      course of management. Practitioners should also be aware of the toxic nature of
      certain antibiotics on the growth fetuses.

PMID- 16432978
TI  - Acute limb ischemia secondary to heparin-induced thrombocytopenia after cardiac
      surgery.
AB  - Heparin-induced thrombocytopenia is an important and sometimes life-threatening
      immunological drug reaction. About 2.5% of patients receiving heparin develop
      immune-mediated (type II) heparin-induced thrombocytopenia that may be
      complicated by a paradoxical thrombotic syndrome either arterial or venous. This
      severe syndrome carries relevant rates of mortality and morbidity secondary to
      cerebral, myocardial and limb infarction. OBJECTIVE: To report two cases of
      successfully treated severe limb acute ischemia secondary to heparin-induced
      thrombocytopenia after cardiac surgery. METHODS: Seven days after aorto-coronary
      bypass and heparin exposure, a 75-year-old female patient developed acute
      ischemia of the left hand and a 60-year-old female patient presented a severe
      ischemia of the left lower extremity. Platelet count level decreased to 12000/mm3
      in the first case and to 11000/mm3 in the second case. RESULTS: The first patient
      underwent emergent fasciotomy of the left hand and forearm and the second one had
      urgent thrombectomy of the left deep femoral, popliteal and posterior tibial
      arteries with venous patch angioplasty. Heparin was discontinued and warfarin
      started few days later. The patients had an uneventful course and they completely
      recovered. CONCLUSION: Early recognition of heparin-induced thrombocytopenia
      syndrome has allowed for significant advances in therapy leading to marked
      reduction in mortality and morbidity. Recently, available thrombin inhibitor
      drugs have dramatically changed outcomes for patients having this severe
      syndrome.

PMID- 16432980
TI  - Urinary tract infections and urosepsis: a physician's guide.

PMID- 16432981
TI  - Urinary tract infections in the pediatric population.
AB  - Urinary tract infections are relatively common in children and are a common
      etiology of fever with absence of other urinary symptoms. It is prudent that the
      pediatricians and urologists perform a correct diagnosis to prevent long-term
      complications of urinary tract infections, particularly renal scaring. The risk
      factors predisposing to urinary tract infections in children are reviewed. We
      also review the clinical presentation, diagnosis, evaluation and therapy.
      Treatment strategies depend on various factors particularly the child's age and
      severity of illness. Specifications of antibiotics to be used also depend on the
      age of the patient and the spectrum of the antibiotic, based on the prevalence of
      organisms at certain ages and in certain situations. Low dose antibiotic
      prophylaxis, an important aspect of therapy for urinary tract infections in
      childhood, is described. The goal of therapy should always be directed to
      prevention of renal scaring and its sequalae including hypertension and renal
      functional deterioration.

PMID- 16432982
TI  - Fungal infections of the genitourinary tract.
AB  - Fungal infections of the urinary tract are increasing in incidence, mostly
      because of the increasing use of antibacterial agents and indwelling urinary
      catheters. This review will focus mainly on the spectrum of genitourinary
      infections caused by Candida spp., including asymptomatic candiduria, cystitis,
      pyelonephritis, and renal candidiasis. Special emphasis will be placed on the
      therapeutic approach to the various clinical entities. Other fungal infections,
      such as urinary aspergillosis and cryptococcosis will be discussed briefly.

PMID- 16432983
TI  - Etiology and medical management of urinary stone disease.
AB  - Urinary lithiasis is a worldwide very frequent disease, but its etiology is most
      frequently unclear. Calcium stones are predominant. The metabolic evaluation of
      urinary lithiasis may be difficult and inconclusive, but it can guide a specific
      treatment. Medical treatment depends on the nature of stone and the metabolic
      disease that might be found. The goal of this article is to simplify and
      summarize the etiopathology, metabolic evaluation and medical treatment of
      urinary stone disease.

PMID- 16432984
TI  - Erectile dysfunction.
AB  - In this era of increased awareness of sexual health, male erectile dysfunction
      has become a primary care issue. Since erectile dysfunction can be either a
      physiologic or psychological problem, the general practitioner needs to be
      prepared for how to approach the evaluation, treatment and overall management for
      their patients. This manuscript will review the epidemiology, definition,
      evaluation, and various treatment modalities for erectile dysfunction, including
      a review of the pharmacologic mechanism of PDE-5 inhibitors such as sildenafil,
      vardenafil, and tadalafil.

PMID- 16432985
TI  - Erectile dysfunction in diabetic patients.
AB  - Erectile dysfunction (ED) appears to be highly prevalent in diabetic patients
      (around 50% at 50 years of age) and more severe than in the rest of the
      population. Its etiology is multifactorial in this subset of patients. ED is
      highly correlated to multiple vascular risk factors and can be considered as a
      manifestation of endothelial dysfunction in general, alerting the physician to
      look at underlying silent coronary bed atherosclerosis. It is also dependent on
      the poor control of diabetes and on the presence of its chronic complications.
      Because of the multiple etiologies of ED in diabetics, a multifactorial approach
      is warranted to get an optimal response in treating such patients: diabetes
      control, use of phosphodiesterase 5 inhibitors, psychosexual counseling, and
      choice of antihypertensive medications.

PMID- 16432986
TI  - Overactive bladder--a practical approach to evaluation and management.
AB  - The overactive bladder (OAB) is a highly prevalent condition characterized by the
      combination of urgency and frequency with or without urge incontinence. The
      pathophysiology is multifactorial; the background is complicated and not yet
      fully understood. The basic diagnostic workup comprises symptoms assessment,
      targeted physical examination, urine analysis, post-void residual urine
      estimation which mostly allows to make a working diagnosis and to find out which
      patients can be treated also by the nonspecialist. The bladder diary is an
      optimal diagnostic instrument with a lot of information, whereas urodynamics are
      expensive and somewhat unverified in their value. The symptom-focused diagnosis
      is absolutely sufficient to start nonoperative therapy for OAB symptoms. The OAB
      presents a treatment challenge, as the management of OAB patients is not
      standardized. An algorithm should include an initial period of at least 6 weeks
      of conservative therapy consisting of antimuscarinic drugs in combination with
      behavioral therapy including pelvic floor exercises. If this combination is not
      successful, the primary diagnosis should be questioned and additional diagnostic
      tests may be required. If the therapy is successful after 8 weeks, a continuation
      should be considered in case the symptoms occur after stopping pharmacological
      therapy. Further therapy depends on the severity of the initial symptoms, the
      presence of side effects and the motivation of the patient. If pharmacotherapy is
      not successful or additional therapy desirable, electrical neuromodulation can be
      added for another period of 6 weeks for up to 3-6 months considering firstly non
      invasive therapeutic modalities before recommending invasive sacral
      neuromodulation. Neuromodulation should be discussed before more invasive
      procedures, such as bladder augmentation, are considered. There are potentially
      promising new therapies on the horizon for the OAB. The use of intravesical
      agents, which decrease the afferent-sensory input, may herald a new therapeutic
      paradigm for the treatment of the OAB. Refinements in the techniques and the
      delivery vehicle for electrical stimulation may offer an even less invasive
      method of neuromodulation. Finally, ongoing research in biotechnology and tissue
      engineering may produce a functional, stable, compatible tissue substitute
      suitable for bladder augmentation. The objectives are (1) to define the
      overactive bladder, (2) to understand the prevalence of the overactive bladder
      and its impact on the quality of life, (3) to review the basic evaluation of the
      patient with symptoms suggestive of the overactive bladder and how to
      differentiate the overactive bladder from other types of urinary dysfunction, and
      (4) to understand the rationale for and the approach to therapy for the
      overactive bladder.

PMID- 16432987
TI  - The cryptorchid testis.
AB  - Advances in surgical technique, pediatric anesthesia and histologic evaluation of
      the cryptorchid testis in conjunction with the known associations with
      infertility, testicular cancer and other risks have led to earlier management of
      the undescended testicle. It is hoped that this paradigm shift will lead to
      improved fertility and decreased risk of malignancy. The results of earlier
      intervention will require future evaluation as the fertility and malignancy
      status of children undergoing orchidopexy today will be unknown for possibly
      decades. We will review the current literature regarding the classification,
      epidemiology, diagnostic approach, and management of cryptorchidism, as well as
      the risks of cryptorchidism including infertility and malignancy.

PMID- 16432988
TI  - Immunosuppression after kidney transplantation: current stragegies and drug
      interactions.
AB  - The success of kidney transplantation has improved over the last decade largely
      due to new immunosuppressive agents that resulted in decrease in incidence and
      severity of acute cellular rejection. Minimizing the adverse effects of
      immunosuppressive agents is essential to improving long-term survival. This
      article reviews the current immunosuppressive agents available to the clinician,
      their side effects and interaction with other medications. Current
      immunosuppressive protocols are also discussed including newer steroid avoidance
      protocols and calcineurin avoidance protocol.

PMID- 16432989
TI  - Evaluation and management of selected sexually transmitted diseases.
AB  - Sexually transmitted diseases (STDs) represent some of the oldest and most
      prevalent infectious diseases of humans. Currently and with changes in
      lifestyles, the short list of STDs has grown to currently comprise 21 different
      infections and infestations. In this review, we concentrate on those infections
      that are common and which require special approach and handling. Gonorrhea and
      nongonococcal urethritis comprise more than half of STDs. The approach and
      management of these patients is briefly outlined. The important role contact
      tracing and education play in improving preventive practices of these infections
      is emphasized. Syphilis is presented in a simplified approach touching on
      presentation, diagnosis and treatment.

PMID- 16432990
TI  - The HepCar registry: report on a one-year registration program of hepatocellular
      carcinoma (HCC) in Belgium. What is daily practice in HCC?
AB  - INTRODUCTION: Due to a rise in HCV induced liver cirrhosis, hepatocellular
      carcinoma becomes more prevalent in Western European countries. The HepCar
      registry is an initiative in which patients with hepatocellular carcinoma, their
      treatment and follow up are registered. MATERIALS AND METHODS: Belgian physicians
      were asked to report all new cases of hepatocellular carcinoma which were seen
      between January 2003 and December 2003. Reporting was done on a voluntary basis.
      Data reported were: demographic figures, the nature of the underlying liver
      disease, presentation characteristics of the tumour, laboratory findings and
      choice of therapy. Every six months, a reminder was sent to determine survival.
      RESULTS: 131 patients (94 male/37 female) were reported. Mean age was 63 years +/
      13. Underlying liver disease was HCV (n = 54, 41%), HBV (n = 22, 17%), alcoholic
      liver disease (n = 39, 30%) and miscellaneous (n =16, 12%). Diagnosis of
      hepatocellular carcinoma was made by surveillance in 47 (36%) patients. After
      logistic regression, survival was 5 times better for patients inside the Milan
      criteria (one lesion less than 5 cm in diameter or less than 3 nodules each less
      than 3 cm in the absence of vascular invasion and metastasis). DISCUSSION:
      Tumours inside the Milan criteria have a better survival. The majority of the
      patients have an underlying cirrhosis as background for the development of a HCC.

PMID- 16432991
TI  - Feasibility of endoscopic ultrasound-guided portal vein embolization with
      Enteryx.
AB  - BACKGROUND: Portal vein embolization (PVE) has been used as a preoperative
      strategy to induce hepatic lobar atrophy and contralateral lobe hypertrophy. We
      determined the feasibility of endoscopic ultrasound (EUS)-guided Enteryx
      (EVAL/ethylene-vinyl alcohol copolymer) embolization of the portal vein (EUS-PVE)
      in an animal model as a potential, minimally invasive, endoscopic technique.
      METHODS: EUS-guided embolization of the portal vein (EUS-PVE) using Enteryx was
      performed in a Yorkshire breed swine. Portal pressure measurements were obtained
      before and after vascular embolization. The animal was carefully monitored for
      seven days for evidence of abdominal pain, shock, or bleeding. An upper abdominal
      contrast-CT scan was performed to verify the location of the embolus. RESULTS:
      The PV pressure increased from 3 mmHg at baseline to a mean of 15 mmHg after EUS
      PVE. The CT-scan on day 4 demonstrated Enteryx in the main portal vein with
      extension into the left branch. At sacrifice on day 7, a solid thrombus was
      visible grossly and histologically inside the main portal vein and the left
      branch of the portal vein. CONCLUSIONS: Selective embolization of the portal vein
      by EUS guidance appears to be feasible and a potential, minimally invasive,
      preoperative treatment option for patients undergoing extensive hepatectomy.

PMID- 16432993
TI  - What is the role of celiac disease in enteropathy-type intestinal lymphoma? A
      retrospective study of nine cases.
AB  - BACKGROUND AND AIMS: It is generally accepted that enteropathy-type intestinal
      lymphoma (EATL) arises against a background of gluten enteropathy. We investigate
      whether patients with this diagnosis had celiac disease or pre-existing celiac
      disease, based on gliadin and endomysium antibodies, as well as duodenal
      biopsies, HLA typing and response to gluten-free diet. METHODS AND RESULTS:
      Retrospective study of patients with the diagnosis of peripheral T cell lymphoma
      of the intestine between January 1990 and January 2002 at the university hospital
      Gasthuisberg Leuven (n = 14). Patients in whom serologic testing was performed or
      patients known with pre-existing celiac disease (CD) were included (n = 9). Six
      of these nine patients were tested for endomysium antibodies (AEM), none of them
      were positive. Of the six patients with biopsies of mucosa uninvolved by
      lymphoma, all of them had villous atrophy; five had increased intraepithelial
      lymphocytes (IEL). In the four patients were HLA typing was performed, the
      results were compatible with CD. The three patients with initially diagnosed
      celiac disease all improved on gluten free diet (control biopsies improved as
      well, but failed to normalise). Of the six other patients, one patient never
      started GFD, two didn't get better, one initially went better after GFD, and one
      went better with the concomitantly started chemotherapy. CONCLUSION: There are
      two possible explanations: Either these patients with EATL have indeed gluten
      intolerance but the sensitivity of AEM is overestimated in this patient
      population; or these patients don't have gluten intolerance and EATL itself can
      mimic CD or other factors mimicking CD are at risk for developing EATL.

PMID- 16432992
TI  - Prokinetic agents in childen with poor appetite.
AB  - BACKGROUND: Of the feeding disorders in children, poor appetite is probably one
      of the most common complaints notified by parents. Since gastric motility
      disorders may be the cause of this symptom, the aim of our study was to
      investigate the effect of prokinetics on children with poor appetite and delayed
      gastric emptying. METHODS: Poor appetite was graded by VAS at start and end of
      treatment. Delayed gastric emptying was assessed by 99mTechnetium tincolloid
      scintigraphy. Malnutrition was defined according to Waterlow criteria. After
      initial assessment behavioural feeding recommendations were provided and
      trimebutine given for 6 months. Scintigraphy was repeated during treatment.
      Anthropometrical measurements and daily energy intake calculations were performed
      monthly RESULTS: 21 children (M/F: 12/9) with a mean age of 7 +/- 3 years were
      studied. At the end of treatment, weight and height standard deviation scores
      improved significantly (-1.0 +/- 0.6 vs. -0.8 +/- 0.7, p = 0.008 and -1.1 +/- 1.0
      vs. -0.8 +/- 0.9, p=0.003, respectively) and malnutrition rate decreased from 81%
      to 66.7%. Improvement of gastric emptying was shown in 11 out of 16 children but
      was not statiscally significant (P = 0.059). The visual analogue scale scores of
      appetite showed significant improvement with therapy (7.5 +/- 1.3 vs. 5.3 +/-
      2.0, p = 0.012). CONCLUSION: Children with poor appetite who have delayed gastric
      emptying might benefit from prokinetic agent therapy combined with behavioural
      feeding recommendations.

PMID- 16432994
TI  - The prevalence of liver function abnormalities in pediatric celiac disease
      patients and its relation with intestinal biopsy findings.
AB  - Abnormal liver function tests and liver damage are seen frequently with celiac
      disease. However, the pathogenesis of liver functions abnormality is not clearly
      understood. The aim of this study was to determine the frequency of abnormal
      liver functions in children with celiac disease and its relation with
      anthropometric measurements and severity of intestinal damage. PATIENTS AND
      METHODS: Twenty seven patients with celiac disease were included in the study.
      Anthropometric and laboratory examinations and intestinal biopsies were performed
      in all the patients. Mucosal lesions were classified according to the Marsh
      classification. Villous area, crypt height and mitotic count were measured
      morphometrically for all biopsy samples. RESULTS: The mean age of patients was 6
      +/- 5 years on admission. Alanine aminotransferase levels were normal (group 1)
      or elevated (group 2) in 20 and 7 patients, respectively. The mean alanine
      aminotransferase levels were 22.0 +/- 7.2 in group 1 and 70.5 +/- 31.1 U/L in
      group 2 patients, (p < 0.001). Complaints, mean age, height for age, weight for
      height, serum albumin level, villous area, crypt height and mitotic count were
      not significantly different between the two groups. Similarly, the ratio of Marsh
      classification was not significantly different between the two groups. All
      patients were given a gluten-free diet. Serum aminotransferase values returned to
      normal after 7.4 +/- 2.7 months of a gluten-free diet. CONCLUSION: Abnormalities
      of liver functions are frequently seen in paediatric celiac disease patients.
      These abnormalities are not correlated with malnutrition and severity of
      intestinal mucosal lesions. Liver enzyme activities return to normal levels in a
      few months after gluten-free diet.

PMID- 16432995
TI  - Non-operative management of endoscopic iatrogenic haemobilia: case report and
      review of literature.
AB  - Haemobilia denotes an abnormal communication between a vessel of the splanchnic
      circulation and the biliary system. Patients typically presents with the triad of
      abdominal pain, upper gastrointestinal haemorrhage, and jaundice. Common causes
      for haemobilia are iatrogenic causes secondary to hepatobiliary system
      instrumentation and trauma. Management of patients with haemodynamic significant
      haemobilia is aimed at stopping bleeding, maintaining continuous flow of biliary
      system, and cure of the underlying aetiology. Iatrogenic haemobilia after ERCP
      polyethylene biliary endoprosthesis placement is extremely uncommon. Herein we
      present a case of iatrogenic haemobilia triggered by biliary endoprosthesis
      placement and was successfully managed by non-operative treatment. The management
      algorithm for a rational approach to haemobilia is discussed.

PMID- 16432996
TI  - Development of sarcoidosis during interferon alpha 2b and ribavirin combination
      therapy for chronic hepatitis C--a case report and review of the literature.
AB  - Sarcoidosis is a chronic granulomatous multisystemic disorder of unknown
      aetiology. Although interferon gamma has been implicated in the pathogenesis of
      sarcoidosis, only a few cases of sarcoidosis associated with interferon alpha
      therapy have been reported. We report a case with chronic hepatitis C (CHC) who
      developed sarcoidosis after the treatment by interferon alpha and ribavirin. The
      combination therapy of interferon alpha and ribavirin was given to a 50-year-old
      female with CHC who had not responded to a previous treatment by interferon
      alpha. She has been admitted with non-productive cough, dyspnoea and fever 11
      months after the initiation of combination therapy. Chest x-ray and thorax
      computed tomography revealed bilateral hilar masses and nodular infiltrations in
      the lung parenchyma. Pulmonary function test showed a mild restriction. Biopsy of
      mediastinal lymphadenopathy revealed noncaseating granuloma. She was diagnosed to
      have pulmonary sarcoidosis at stage II, and the combination treatment was
      discontinued. Her symptoms regressed after inhaler steroid treatment. Six months
      after the diagnosis of sarcoidosis, the patient was asymptomatic and a complete
      sustained response to hepatitis C was achieved. During the three years of follow
      up, both pulmonary sarcoidosis and hepatitis C have not recurred. We suggest that
      sarcoidosis may develop in chronic hepatitis C patients during interferon alpha
      and/or ribavirin treatment, and diagnostic tests for this adverse effect should
      be performed during the follow-ups.

PMID- 16432997
TI  - Tertiary syphilis presenting as hepatic bull's eye lesions.
AB  - We report a rare case of tertiary syphilis (hepatic gummata, asymptomatic
      neurosyphilis and iridocyclitis) in a 47 year old female patient. Our patient
      suffered from a troubled sight, pain in the right hypochondrium, one enlarged
      submandibular lymph node, an elevated sedimentation rate, disturbed liver tests
      and two hepatic lesions upon abdominal computed tomography. The diagnosis was
      based upon a liver biopsy and a positive Treponema Pallidum haemagglutination
      test. The patient was treated with doxycyclin. After treatment the sedimentation
      rate and liver tests normalised and the hepatic lesions disappeared leaving a
      small 'scar' on CT-scan; at the end she still complained of a decreased sight. We
      conclude that syphilitic gummata of the liver have a favourable prognosis when
      the diagnosis is made early. One has to differentiate with hepatic abscesses,
      primary tumours and metastases.

PMID- 16432998
TI  - Gallbladder adenosquamous cell carcinoma: report of two cases.
AB  - Adenocarcinoma is the usual histological presentation of the very rare
      gallbladder carcinoma. Adenosquamous cell carcinoma accounts for less than 3.5%
      of gallbladder carcinomas, and is characterised by invasive growth, a reduced
      tendency for lymph node metastasis, an increased tendency for hepatic
      infiltration or liver metastasis, and a poorer prognosis than adenocarcinoma. We
      present two cases. The first patient presented to our institution with increased
      bilirubin levels and dilated intra- and extrahepatic bile ducts. Adenosquamous
      carcinoma of the gallbladder was diagnosed on the post-operative pathological
      specimen. After surgery, bilirubin levels decreased, but hepatic metastases
      occurred that did not respond to conventional chemotherapy. The second patient
      was admitted to our hospital with jaundice and abdominal pain. Abdominal computed
      tomography (CT) imaging showed marked thickening of the gallbladder with direct
      extension of a mass into the left liver lobe. Cytology specimens obtained with an
      endoscopic retrograde cholangiopancreatography (ERCP) procedure revealed a
      malignant epithelial tumour. The patient underwent surgery but the tumour was
      incompletely resected. A regimen of oral UFT (Tegafur + uracil) chemotherapy was
      begun. Serum bilirubin levels increased due to occlusion in the surgical area 15
      weeks after the start of chemotherapy.

PMID- 16433000
TI  - A review of conservative and surgical management of anal fissure.
AB  - BACKGROUND: Anal fissures are one of the common perianal conditions presenting
      with bleeding, itching, and pain of varying severity. The method of treating this
      pathology should preferably be the one that results in optimal clinical outcome,
      is less painful, and is patient friendly. Despite a plethora of techniques in
      vogue, an ideal management of this condition continues to be a subject of debate.
      MATERIALS AND METHODS: A Medline database was used to perform a literature search
      for articles relating to the term 'anal fissure'. CONCLUSION: Analysis of the
      available literature shows that by far, medical manipulation of the internal
      sphincter should be the first-line treatment in anal fissure. A surgical therapy
      is called for if the medical therapy fails or there is a recurrence.

PMID- 16432999
TI  - Recurrent colonic Dieulafoy's lesion associated with bizarre vascular
      malformations and abnormal von Willebrand factor.
AB  - Colonic Dieulafoy's lesion is an unusual source of massive lower gastrointestinal
      haemorrhage. It is characterized by severe bleeding from a minute submucosal
      arteriole that bleeds through a punctuate erosion in an otherwise normal mucosa.
      We describe an elderly man who presented recurrent rectal bleeding from a
      Dieulafoy's lesion in the sigmoid colon associated with bizarre colonic vascular
      malformations and an abnormal von Willebrand Factor. He was successfully treated
      by endoclips application. The clinicopathologic features of this unusual
      association are discussed and suggestions are made for diagnosis and management.

PMID- 16433001
TI  - Introduction: liver and liver cell transplantation for inborn errors of liver
      metabolism.

PMID- 16433002
TI  - Long-term complications of immunosuppression in pediatric liver recipients.
AB  - Liver transplantation (LT) today constitutes a well-standardized and efficient
      therapy for children with acute and chronic hepatic failure. Appropriate pre
      transplant management, organ preservation, adequate surgical techniques, and the
      progressive introduction of new immunosuppressive regimens have contributed to
      significantly improve, over the years, the general outcome after LT.
      Consequently, these good overall results has allowed the constitution of a
      growing cohort of children, adolescents and young adults submitted to chronic
      immunosuppression. The long-term complications of immunosuppression administered
      to transplant recipients include the adverse effects secondary to the depression
      of the immune system, the toxicities specifically related to the individual
      immunosuppressive drugs, and the sense of lack of rehabilitation for the
      transplant patient, with, secondarily, the question of non-adherence to the
      medications. This review will essentially focus on these three issues in the
      particular context of pediatric liver transplantation.

PMID- 16433003
TI  - Hepatocyte transplantation for metabolic disorders, experience at King's College
      hospital and review of literature.
AB  - Hepatocyte transplantation is emerging as a potential treatment for liver based
      metabolic disorders and acute liver failure. To date, clinical studies have shown
      that hepatocyte transplantation could be used as a "bridge" to liver
      transplantation in a few patients with acute liver failure and has changed the
      phenotype of metabolic patients in terms of reducing the severity of illness. For
      many years, research studies have been carried out to optimise conditions for a)
      hepatocyte isolation in order to obtain the highest possible number of viable
      hepatocytes isolated from various sources of unused donor liver tissues, and b)
      cryopreservation and storage of hepatocytes for immediate cell availability in
      emergency cases. In this review, we summarise the worldwide clinical experience
      in hepatocyte transplantation for liver based metabolic disorders including the
      experience of our centre at King's College Hospital, London (United Kingdom). We
      briefly comment on the possible future developments and improvements needed in
      this field.

PMID- 16433004
TI  - Adult stem cells--perspectives in treatment of metabolic diseases.
AB  - There is currently great excitement and expectation concerning the differential
      potential of adult stem cells or adult cells with capacity of differentiation. As
      the body of work concerning transdifferentiation of somatic stem cells and bone
      marrow derived stem cells grows, the number of critics increases steadily
      questioning the reliability of reported findings. So scientists are now
      challenged more and more to prove that resulting differentiated somatic cells
      originated from somatic adult stem cell through a transdifferentiation process.
      Phenomenons such as fusion of cells have to be ruled out and the origin of the
      differentiated cell has to be determined by specific techniques i.e. in situ
      hybridisation. Cellular mimicry through uptake of specific factors out of the
      medium is questioned to be the reason for cells staining positive for Insulin.
      Some multipotent adult stem cells can cross lineage boundaries and differentiate
      into somatic cells of other lineages after being relocated. Bone marrow cells
      have been described to have the greatest plasticity among adult stem cells
      regenerating damaged liver or myocardium. It has been proposed that the
      differentiation of bone marrow derived adult stem cells occurs naturally even in
      healthy organs as a physiologic process of tissue-regeneration. Others believe
      that organ damage is essential to induce transdifferentiation by release of organ
      specific microenvironmental factors. We here try to constitute necessary data
      which should be demonstrated to give substantial evidence for
      transdifferentiation of newly characterized cells including exclusion of fusion,
      phagocytosis or DNA uptake, description of the outset cell, differentiation into
      all three germ layers and functional parameters.

PMID- 16433005
TI  - Long-term outcome of urea cycle disorders.
AB  - Evaluation of long-term outcome of patients with urea cycle diseases (UCD) is
      needed for medical decisions and counselling. Own data comparing outcome of UCD
      patients with the old treatment limited to protein restriction (i.e. close to the
      natural history) with that of patients on the modern conservative treatment have
      shown that gains in survival occur at the cost of more mentally retarded
      surviving patients. We discuss the possible bias in long-term outcome studies of
      those rare inheritable disorders where non-predictable environmental factors
      leading to catabolic crises have a crucial impact on prognosis. A combination of
      peak or initial ammonia value combined with the duration of coma is discussed as
      a criterion for prognosis of handicap. The neglect of dietary compensation of
      branched chain amino acid deficiency worsened by phenylbutyrate treatment in some
      published protocols could well be an additional cause of the non satisfactory
      long-term results of conservative treatment which--in our view--mainly aim at
      bridging optimally the period of late neonatal presentation until liver
      transplantation in patients with CPS and OTC deficiency (except for mild forms).

PMID- 16433006
TI  - Liver and liver cell transplantation for glycogen storage disease type IA.
AB  - Glycogen storage disease type Ia (GSDIa) is an inherited disorder of glucose
      metabolism, due to the selective deficiency of the hepatic enzyme glucose-6
      phosphatase. Clinical manifestations include severe hypoglycaemia three to four
      hours post-prandially, increased production of lactic acid, triglycerides and
      uric acid, hepatic glycogen storage disease with development of multiple adenomas
      and kidney disease with proteinuria. Liver transplantation is frequently
      performed in order to achieve metabolic control and when malignant transformation
      of adenomas is suspected. Long term outcome following transplantation is good,
      but immunosuppressive therapy can worsen the progression of associated kidney
      disease. Hepatocyte transplantation could be considered as a less invasive
      procedure in such patients. Our experience with hepatocyte transplantation in a
      47 year-old woman affected by glycogen storage disease type Ia and suffering of
      severe fasting hypoglycaemia indicates that the procedure can partially correct
      some metabolic abnormalities and improve the quality of life in this disease.
      However, the metabolic improvement was reduced and finally abolished during long
      term follow-up, probably due to rejection or to senescence of transplanted cells.
      Moreover, the portal and pulmonary hypertension associated with the disease need
      to be evaluated for their possible influence on haemodynamic changes associated
      with cell infusion. Finally, hepatic adenomas need careful monitoring because of
      the possible risk of malignant transformation.

PMID- 16433007
TI  - Usefulness of flash-light transillumination button on videoendoscopy system for
      percutaneous endoscopic gastrostomy (PEG) tube insertion.

PMID- 16433008
TI  - [Depression, yesterday, today and tomorrow: historical evolution of concepts].
AB  - Depressive thoughts have been apparent since the origins of humanity. References
      to depressive thoughts can be found in philosophical writings and other
      literature since antiquity. They were always approached in a religious or medical
      way, with arguments for a mix of psychological and mystical origins. With the
      advent of psychiatry as a medical discipline, depressive syndromes were
      integrated into classifications of mental disorders. The definition of depression
      is multifactorial, integrating psychosocial, social and biological factors. In
      this article we use an historical perspective to describe the sociological,
      psychopathological and biological concepts relating to depressive illness. Over
      one century, the sociology of mental illness has evolved from the Durkheimian
      position to psychosocial models which incorporate environmental stressors, social
      support and coping mechanisms. Psychology encompasses psychoanalytical, cognitive
      behavioural and phenomenological theories. Finally, biological psychiatry
      suggests various approaches--genetic, biochemical, neurophysiological,
      neuroanatomical.... The therapeutic directions are central to these concepts,
      just like public health, which seeks to promote the concept of mental health
      rather than to limit itself to the definition of the various psychiatric
      disorders.

PMID- 16433009
TI  - [Neurobiology of depression: new data].
AB  - Monoaminergic systems, and in particular serotoninergic neurons of the raphe
      system, have been involved in the physiopathology and treatment of major
      depression in a great number of studies. One of the most reproducible effects of
      antidepressant treatment is the increase of central 5-HT (serotonin) tone.
      However, the identification of novel potential therapeutic targets
      (neurohormones, neuropeptides) for treating depression has led to elaborating
      novel cellular and molecular concepts accounting for stress-related mood
      disorders. In particular, recent studies have demonstrated that chronic
      administration of all classes of antidepressants up-regulates neurogenesis in
      adult rodent hippocampus. The possibility that structural remodelling may
      contribute to the physiopathology of mood disorders provides new avenues of
      research toward understanding the cellular basis of mood disorders.

PMID- 16433010
TI  - Serotonin 5-HT2C receptors as a target for the treatment of depressive and
      anxious states: focus on novel therapeutic strategies.
AB  - Serotonin (5-HT)2C receptors play an important role in the modulation of
      monoaminergic transmission, mood, motor behaviour, appetite and endocrine
      secretion, and alterations in their functional status have been detected in
      anxiodepressive states. Further, 5-HT2C sites are involved in the actions of
      several classes of antidepressant. At the onset of treatment, indirect activation
      of 5-HT2C receptors participates in the anxiogenic effects of selective 5-HT
      reuptake inhibitors (SSRIs) as well as their inhibition of sleep, sexual
      behaviour and appetite. Conversely, progressive down-regulation of 5-HT2C
      receptors parallels the gradual onset of clinical efficacy of SSRIs. Other
      antidepressants, such as nefazodone or mirtazapine, act as direct antagonists of
      5-HT2C receptors. These observations underpin interest in 5-HT2C receptor
      blockade as a strategy for treating depressive and anxious states. This notion is
      supported by findings that 5-HT2C receptor antagonists stimulate dopaminergic and
      adrenergic pathways, exert antidepressant and anxiolytic actions in behavioural
      paradigms, and favour sleep and sexual function. In addition to selective
      antagonists, novel strategies for exploitation of 5-HT2C receptors embrace
      inverse agonists, allosteric modulators, ligands of homo/heterodimers, modulators
      of interactions with 'postsynaptic proteins', dual melatonin agonists/5-HT2C
      receptor antagonists and mixed 5-HT2C/alpha2-adrenergic antagonists.
      Intriguingly, there is evidence that stimulation of regionally discrete
      populations of 5-HT2C receptors is effective in certain behavioural models of
      antidepressant activity, and promotes neurogenesis in the hippocampus. This
      article explains how these ostensibly paradoxical actions of 5-HT2C antagonists
      and agonists can be reconciled and discusses both established and innovative
      strategies for the exploitation of 5-HT2C receptors in the improved management of
      depressed and anxious states.

PMID- 16433011
TI  - [Depression and neuroplasticity: implication of serotoninergic systems].
AB  - Neuroplasticity contributes to both normal and pathological brain function. A
      recent hypothesis links depression to lack of adaptive responses to stress or
      other aversive stimuli, and effects of antidepressant treatments on adult
      neurogenesis are more and more extensively studied because of the structural
      changes involved in the pathophysiology of depression. Indeed, neuronal
      remodelling in hippocampal formation is associated with chronic stress and is
      reversed by antidepressant treatments in animals. Decrease in hippocampal volume
      has also been associated to cognitive deficits in patients with major depression.
      Interestingly, serotonergic (5-HT) systems play a major role both as
      antidepressants and by increasing hippocampal neurogenesis through various
      receptor subtypes. Recently, we have also demonstrated that agomelatine, a new
      antidepressant drug having serotonergic and melatonergic properties, can increase
      proliferation and survival of newly formed hippocampal cells. Although the
      mechanisms underlying such effects are still unknown, these data reinforce the
      view that changes in hippocampal neurogenesis might belong to the cellular
      correlates of mood disorders.

PMID- 16433013
TI  - Behavioural models for the characterisation of established and innovative
      antidepressant agents.
AB  - To improve the management of depressive states, it is essential to develop
      preclinical behavioural models for the characterisation of both conventional and
      new antidepressant agents. This need is illustrated in this article with two very
      different classes of antidepressant agents, serotonin and/or noradrenaline
      reuptake inhibitors (SNRIs) and neurokinin NK1 receptor antagonists. Their
      effects are evaluated in rodent models of (i) the detection of potential
      antidepressant activity via marble-burying behaviour in mice; (ii) drug
      discrimination procedures in rats (mechanistic); and (iii) the evaluation of
      potential activity on co-morbid symptoms, such as anxiety, via the social
      recognition test in rats and gerbils. It is concluded that behavioural assays
      offer a palette of techniques for the characterisation of clinically active
      antidepressants as well as for innovative (acting on new targets) or improved
      (multi-target) antidepressants. Nevertheless, for antidepressants of the future,
      as for established antidepressants, feedback from clinical trials are awaited to
      confirm the predictive value of these models.

PMID- 16433012
TI  - [Mechanism of action of antidepressant drugs: importance of genetically modified
      mice in the pharmacological in vivo approach].
AB  - The main hypothesis regarding the mechanism of action of antidepressant drugs is
      monoaminergic and mainly involves two neurotransmitters, serotonin and
      noradrenaline. Despite the well-recognized therapeutic efficacy of selective
      serotonin reuptake inhibitors (SSRIs), some disadvantages still occur. For
      example, they often require 4-6 weeks to achieve clinical benefits in depressed
      patients. In the past, some molecules that could shorten this long delay of
      action have been identified. The role of presynaptic autoreceptors - the
      activation of which leads to an inhibitory feedback control on neurotransmitter
      synthesis and release - has been extensively studied for antidepressant effects.
      In our laboratory, we studied the combined effects of an SSRI and a serotonin
      autoreceptor antagonist of the 5-HT1B subtype using intracerebral in vivo
      microdialysis in awake, freely moving mice. Important information on SSRIs has
      been obtained by applying this technique to genetically modified animals, such as
      constitutive knockout (KO) mice lacking 5-HT1B receptors (5-HT1B KO) generated by
      homologous recombination: we compared the effects of a combined treatment on
      extracellular/intrasynaptic levels of serotonin in various nerve terminals area
      in wild-type control and KO mice. Thus, we found that indirect activation of 5
      HT1B autoreceptors limits the effects of SSRIs on dialysate 5-HT levels at
      serotonergic nerve terminals such as the ventral hippocampus. The study of
      substance P (neurokinin 1 receptor [R-NK1]) offers another example of the use of
      KO mice in the development of a new class of antidepressant drugs. NK1 receptor
      antagonists may display anxiolytic/antidepressant-like properties. The lack of
      selective compounds for each tachykinin receptor subtype (R-NK 1, R-NK2 or R-NK3)
      and differences in their affinity between animal species have made R-NK1 KO mice
      a very useful experimental tool. In collaborative work we found that genetic (R
      NK1 KO mice) or pharmacological (GR205171) blockade of R-NK1 is associated with
      several changes: the increase in cortical 5-HT outflow caused by systemic
      injection of paroxetine was 4- to 6-fold higher in freely moving R-NK1 KO mice
      than in wild-type controls. The constitutive lack of NK1 receptors is associated
      with a functional desensitization of somatodendritic 5-HT1A autoreceptors,
      resembling that induced by chronic treatment with SSRI antidepressants. These
      results highlight the link between a neurotransmitter (serotonin) and a
      neuropeptide (substance P). This genetic strategy allowed us to point out that
      multiple targets participate to the effects of classical antidepressant drugs
      within the brain. We hope that, soon, some mice lines (constitutive or tissue
      specific, conditional rescue mice having alterations of sleep/wakefulness and/or
      food intake, altered central serotonin and/or noradrenaline neurotransmission,
      deficit in neurotrophic factors, but increases in intrasynaptic concentrations of
      substance P) could be a relevant model of the physiopathology of depressive
      disorders, and could help us understand the appearance of some symptoms. These
      recent findings suggest that instead of being rejected, the monoaminergic
      hypothesis of depression should be improved, corrected and completed by studying
      the role of other neurotransmitter, neuromodulatory compounds (substance P, BDNF
      [brain-derived neurotrophic factor]). By doing so, it thus could be possible to
      improve antidepressant drug treatment, i.e. shorten their long delay of action
      and/or to decrease treatment resistance or improve its tolerance.

PMID- 16433014
TI  - [Methods: scales, biological and clinical criteria].
AB  - Assessing depressive symptomatology in antidepressant drug trials is limited by
      the absence of external validators of depression. Moreover, a high level of
      standardisation is required by regulatory authorities for registering new drugs.
      Consequently, the methods used are relatively old, and recent improvements have
      been minor. Methods used to assess new antidepressants appear highly standardised
      and lack objectivity. Improvements to these methods may emerge from the discovery
      of external validators of depression on the one hand and of drugs with new
      mechanisms of action on the other.

PMID- 16433016
TI  - [Hydration of patients treated with cisplatin: practical investigation and
      establishment of a protocol].
AB  - BACKGROUND: Administration of cisplatin requires hyperhydration of the patient to
      prevent nephrotoxic effects of this molecule. MATERIALS AND METHODS: A survey
      done in different hospitals - university hospitals, general hospitals and cancer
      institutes--has shown a large variability in the hydration protocols. A
      multidisciplinary group was set up in our university hospital comprising
      oncologists, nephrologists and pharmacists. This group has developed a consensual
      local protocol from a bibliographic analysis (Medline) and from the personal
      experience of each member. CONCLUSION: This protocol was approved by our
      hospital's Committee of Drugs and Medical Devices.

PMID- 16433015
TI  - [Therapeutic strategies for depression].
AB  - To date, no one antidepressant medication has been proven to be more efficient
      than another. Physicians are still waiting for good criteria to select which
      antidepressant has more chances of being effective in certain patients.
      Nevertheless, guidelines for antidepressant prescription could improve the rate
      of success in treating depression. All antidepressant medications share the same
      indication: a major depressive episode. Some compounds have indications other
      than a major depressive episode, which may be taken into account by the
      prescribing physician. Many researchers have tried to identify predictive
      criteria of response to antidepressants. The predictive clinical criteria
      include: endogeneity, early response, severity and duration of depression,
      pathological personality traits, quality of the environment, and co-morbid
      organic abnormalities. Paraclinical criteria have also been studied: levels of
      monoamines, neuro-endocrinological parameters, enzymatic activities,
      polysomnography, and brain imaging. Different recommendations have been proposed
      to guide therapeutic strategies from the acute period to the post-acute period,
      but three items have been mentioned most often: risk of negative side effects,
      patient expectations, and level of proof of efficacy of the compounds. Mild to
      moderate major depressive episodes raise a difficult question: can psychotherapy
      be an alternative option to antidepressant medication?

PMID- 16433017
TI  - [Drugs contraindicated in children: a study of drug prescriptions in ambulatory
      medicine in the south of France (Aude Department)].
AB  - AIMS: The aim of this study was to describe prescriptions of drugs contra
      indicated in children according to the summary product characteristics (SPC) of
      the drugs. METHODS: An exhaustive cross-sectional study based on the data used by
      the French Health Insurance in the Aude Department (France) during 2001 was
      carried out to identify all instances where children under the age of 15 years
      were prescribed a drug that stated in its SPC that its use in this age group was
      contraindicated. RESULTS: The prescription of drugs stated as being
      contraindicated in children under the age of 15 years involved 4316 children. The
      incidence rate was 116 per 1000 child-years. It was patently obvious for two
      classes of drugs: nasal decongestants (21.0% of prescriptions) and non-steroidal
      anti-inflammatory drugs (16.9%). These prescriptions were made by 610 physicians,
      of which 70% were general practitioners, 8% dentists and 3% paediatricians.
      CONCLUSION: This study shows a high incidence of children receiving
      contraindicated drugs in Aude department in France. This work highlights the need
      for, first, the widespread dissemination of information on the good use of drugs
      in children and, secondly, specific clinical trials performed in children.

PMID- 16433018
TI  - [Diffusion of pharmacist interventions within the framework of clinical pharmacy
      activity in the clinical ward].
AB  - BACKGROUND: Computerised physician order entry (CPOE) and the integration of a
      pharmacist in clinical wards have been shown to prevent medication errors.
      OBJECTIVES: The objectives were to describe interventions performed by a clinical
      pharmacist integrated into clinical wards with CPOE, to assess the acceptance of
      interventions by prescribers, and to describe factors associated with acceptance.
      METHODS: A 3-week prospective study was conducted in five wards of a 2000-bed
      French teaching hospital. RESULTS: During pharmacist review of medication orders
      and participation on physician rounds, six resident pharmacists provided
      interventions either conveyed orally to prescribers, using the computer system,
      or combining both methods. There were 221 pharmacist interventions concerning
      drug-drug interactions (27%), drug monitoring (17%) and computer-related problems
      (16%). Pharmacist interventions consisted of change of drug choice or dose
      adjustment (49%), drug monitoring (17%) and administration modality optimisation
      (14%). Interventions were provided solely via computer systems in 67% of cases.
      The rate of intervention acceptance was 47.1%. In multivariate analysis,
      acceptance was significantly associated with oral transmission (odds ratio [OR] =
      6.46; 95% confidence interval [95% CI] [1.65-25.24]; p < 0.01), change of drug
      choice or dose adjustment recommendations (OR = 3.81; 95% CI [1.63-8.86]; p <
      0.01) and administration modality optimisation recommendations (OR = 9.51; 95% CI
      [3.02-29.93]; p < 0.01). CONCLUSION: Communication method and nature of
      recommendation are factors associated with pharmacist intervention acceptance.
      CPOE is necessary to develop clinical pharmacy practice. However, only the
      integration of the pharmacist on the ward can guarantee a high level of
      acceptance of pharmacist interventions by prescribers.

PMID- 16433019
TI  - [Allergic reactions to paracetamol].
AB  - BACKGROUND: Paracetamol is an extensively used analgesic and antipyretic. Allergy
      to this drug is occasionally reported and is usually moderate. MATERIALS AND
      METHODS: We led a retrospective study of 119 cases of allergic reactions to
      paracetamol notified to the Tunisian centre of pharmacovigilance, between
      September 1990 and September 2000. These cases were validated according to the
      method of imputability of Begaud et al. RESULTS: Our population comprised 64
      women and 55 men, aged 1 month to 70 years. Antecedents of allergy or atopy were
      found in many cases, including 10 cases of allergy to paracetamol and 6 to
      salicylates. Paracetamol was self-administered in 50% of cases and taken with
      other drugs in 68% of cases. The type of lesions varied, the most frequent being
      urticaria (34.4%), macular and pustular eruption (30.2%) and fixed drug eruption
      (12.6%). Some reactions were serious, such as Lyell syndrome or anaphylactic
      shock. Resolution was favourable in all cases and paracetamol was definitively
      contraindicated for patients with scores of high or mild imputability.
      CONCLUSION: Allergy to paracetamol seems to be rare but not exceptional. Several
      risk factors seem to be important in triggering this side effect, particularly
      antecedents of allergy to this drug or to aspirin.

PMID- 16433020
TI  - Changes in cholinergic and purinergic neurotransmission in the diabetic rabbit
      bladder.
AB  - BACKGROUND: Diabetes mellitus (DM)-associated alterations in bladder function
      have been attributed to changes in autonomic receptors and alterations in
      detrusor structure and function. The changes in cholinergic and purinergic
      neurotransmission in the DM rabbit bladder were evaluated. MATERIALS AND METHODS:
      DM was induced with alloxan in adult male New Zealand White rabbits. At 6 months,
      detrusor and bladder neck muscle strips were obtained and mounted in organ baths.
      Transmural electrical field stimulation (EFS: supramaximal voltage, 0.1 ms
      duration, 10 s trains) was performed in the presence of atropine (10(-6) M) or
      alpha, beta-methylene ATP (10(-6) M), and after adding tetrodotoxin10(-6) M.
      Purinergic, alpha, beta-methylene ATP-sensitive, and cholinergic, atropine
      sensitive, components were calculated independently and compared with those from
      controls. RESULTS: Both normal and DM detrusor and bladder neck strips contracted
      in a frequency-dependent fashion in response to transmural EFS. A plot of EFS vs.
      detrusor contractility showed a decrease (ANOVA < 0.001) in the cholinergic nerve
      mediated component, whereas the purinergic nerve-mediated component was increased
      (ANOVA < 0.001) in the DM detrusor compared to the control. The total EFS- and
      KCl-induced responses were unaltered in the DM group compared to the controls.
      There was no difference in purinergic, alpha, beta-methylene ATP-sensitive, and
      cholinergic, atropine-sensitive, components in strips from the bladder neck for
      both normal and DM rabbits. CONCLUSION: These results suggest that an enhancement
      of purinergic and a reduction of cholinergic neurotransmission occur in the
      detrusor muscle of the diabetic rabbit. These changes may contribute to the
      pathophysiology of diabetic cystopathy.

PMID- 16433021
TI  - Effects of gender and gonad status on N-methyl-N-nitrosourea-induced
      cataractogenesis and retinopathy in Lewis rats.
AB  - BACKGROUND: The effects of differences in gender and gonadal status on the
      occurrence of N-methyl-N-nitrosourea (MNU)-induced cataract and retinopathy were
      studied using ovary-intact, ovariectomized, testis-intact and testectomized Lewis
      rats. MATERIALS AND METHODS: Castration was performed at 36 days of age, 50 mg/kg
      MNU was administered intraperitoneally at 50 days of age, and lens and retinal
      changes were evaluated at 260 days of age (210 days after MNU injection).
      RESULTS: Although there was little difference in the incidence of cataract and
      retinopathy among the groups, ovary-intact rats had a significantly higher
      cataract index and retinal damage ratio (both are indicators of disease severity)
      than ovariectomized rats and testis-intact rats, respectively. However, the
      cataract index and retinal damage ratio did not correlate with the serum 17beta
      estradiol and progesterone levels, respectively. CONCLUSION: The presence of
      ovaries and female gender appear to be associated with greater severity of
      cataracts and retinopathy, respectively, but the severity of these diseases did
      not correlate with the serum hormone levels.

PMID- 16433022
TI  - Comparison of xenografting in SCID mice and LIVE/DEAD assay as a predictor of the
      developmental potential of cryopreserved ovarian tissue.
AB  - This study compared the predictive value of the LIVE/DEAD fluorescence viability
      assay to xenotransplantation in SCID mice, regarding the developmental potential
      of cryopreseved human ovarian tissue for fertility preservation purposes. The
      thawed ovarian tissue of ten patients was partly examined by LIVE/DEAD viability
      staining or histologically examined after transplantation and gonadotropin
      stimulation in 30 SCID mice. The LIVEIDEAD assay showed 87.1 +/- 3.5% (mean +/
      SD, n=10) viable follicles (intact oocyte and more than 50% of granulosa cells
      alive). Histological examination showed follicles in all developmental stages in
      the transplanted grafts. The total number of follicles found was much lower than
      with the LIVE/DEAD assay (8.9 +/- 3.1 versus 54.4 +/- 20.0, p < 0.001). If the
      LIVE/DEAD assay yields > approximately 85% viable follicles, it can be assumed
      that the follicles in the cryopreserved tissue have maintained their
      developmental potential. This assay is, therefore, a suitable diagnostic method
      before an intended retransplantation.

PMID- 16433023
TI  - HuR, an RNA-binding protein, involved in the control of cellular differentiation.
AB  - HuR is an RNA-binding protein that resides predominantly in the nucleus but
      shuttles to the cytosol carrying mRNAs containing a uridylate-rich region in the
      3'untranslated region. Data suggest that HuR is involved in the control of the
      differentiation process through a tightly regulated selection of mRNAs to be
      shuttled to the cytosol for translation. In this review, the function of HuR in
      the differentiation process of preadipocytes is examined in the context of
      specific mRNAs selected by HuR for translocation to the cytosol.

PMID- 16433024
TI  - In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline and green
      tea extract on human melanoma cell line A2058.
AB  - BACKGROUND: Melanoma, a very serious form of skin cancer, causes the most skin
      cancer-related deaths, due to metastasis. Structural changes in the extracellular
      matrix (ECM) are necessary for cell migration during tissue remodeling. MMPs,
      VEGF, Ki-67 (proliferative protein) and constituents of ECM play a critical role
      in angiogenesis, and are crucial in neoplastic invasion and metastasis. MATERIALS
      AND METHODS: The effect of a diet (NM) containing lysine, proline, arginine,
      ascorbic acid and green tea extract on the growth of tumors induced by implanting
      human melanoma A2058 cells in athymic nude mice was examined and, also, on the
      expression of MMPs, VEGF and Ki-67 in these tumors. The effect of NM in vitro on
      the melanoma A2058 cell line was tested by measuring: cell proliferation by the
      MTT assay, expression of MMPs by gelatinase zymography and invasion through
      Matrigel. RESULTS: Nutrient supplementation strongly suppressed the growth of
      tumors (by 57%)without adverse effects in nude mice. Histological studies
      supported these findings by showing inhibition of MMP-9 and VEGF secretion and
      mitotic index. In vitro, NM inhibited melanoma cell growth by 64% at 500
      microg/ml and Matrigel invasion by 95% at 100 microg/ml NM. CONCLUSION: These
      results suggest that NM may have a therapeutic potential in melanoma.

PMID- 16433026
TI  - Anti- and pro-oxidant effects of oxidized quercetin, curcumin or curcumin-related
      compounds with thiols or ascorbate as measured by the induction period method.
AB  - Phenolic antioxidants, such as quercetin (QUE), curcumin (CUR) and the CUR
      related compounds eugenol (EUG) and isoeugenol (IsoEUG), do not act in isolation
      in vivo but form an intricate antioxidant network together with ascorbate or
      glutathione (GSH). To clarify the antioxidant/prooxidant activity of these
      compounds in their interplay with ascorbate or GSH, the induction period (IP) and
      propagation rate (Rp) for mixtures of 2-mercapto-1-methylimidazole (MMI, a thiol)
      or L-ascorbyl-2,6-dibutyrate (ASDB, an ascorbate derivative) with QUE, CUR, EUG
      or IsoEUG were determined from differential scanning calorimetry (DSC) monitoring
      of the polymerization of methyl methacrylate (MMA), initiated by thermal
      decomposition of 1.0 mol% benzoyl peroxide (BPO, a PhCOO* radical) under nearly
      anaerobic conditions. The IP (min) for 0.01 mol% test compounds declined in the
      order CUR (28.31) > IsoEUG (19.47) > EUG (16.83) > QUE (10.17) > MMI (2.06) >
      ASDB (0.16). The inhibition rate constant (kin(inh), M(-1)s(-1)) declined in the
      order ASDB (7.85 x 10(5)) > MMI (5.99 x 10(4)) > QUE (1.21 x 10(4)) > EUG (7.93 x
      10(3)) > IsoEUG (7.04 x 10(3)) > CUR (4.50 x 10(3)). The observed IP for MMI/QUE
      mixtures, particularly at molar ratios of 2:1 and 5:1, was significantly less
      than that for QUE alone as well as that calculated for MMI/QUE. The decrease in
      IP was similar to the observed IP in the control, suggesting the occurrence of
      oxygen uptake, possibly due to the formation of thiol RS radicals which, together
      with oxygen, produce oxo- and peroxo-sulphur radicals. The observed IPs for
      MMI/CUR or the MMI/IsoEUG mixtures, particularly the former, were less than the
      corresponding calculated IPs, suggesting co-oxidation of the MMI without oxygen
      uptake. In contrast, the observed IP of MMI/EUG mixtures was much greater than
      the corresponding calculated IP, suggesting the formation of an new antioxidative
      adduct between EUG-quinonemethide and MMI. The observed IP for the ASDBI/QUE
      mixtures was greater than the corresponding calculated IP, suggesting the
      effectiveness of QUE as a co-antioxidant for ascorbate. In contrast, the observed
      IP for the ASDB/CUR mixtures was significantly less than the corresponding
      calculated IP, suggesting the catalytic effectiveness of CUR for ascorbate co
      oxidation. Cancer cells are anaerobic in their metabolism and they selectively
      absorb more ascorbate than normal cells do. Thus, the present findings for the
      ASDB/CUR mixtures could help explain the effectiveness of CUR in chemoprevention
      by inducing cancer cell apoptosis. In addition, the findings for the MMI/QUE
      mixtures suggest the production of toxic oxo- and peroxo-sulphur radicals from
      thiols.

PMID- 16433025
TI  - Effects of neonatally-administered 17beta-estradiol on induction of mammary
      carcinomas by 7, 12-dimethylbenz[a]anthracene in female rats.
AB  - Various doses of 17beta-estradiol (E2) were administered subcutaneously to inbred
      female Sprague-Dawley (SD) rats once at birth. At 50 days after birth, rats in
      all the groups were given 10 mg of 7, 12-dimethylbenz[a]anthracene (DMBA). In the
      1000 microg group, the incidence and number of mammary carcinomas were markedly
      low, while in the 10 microg group, a large number of mammary carcinomas was
      noted. Corpora lutea were observed in all rats in the control, 0.1, 1, 10 and 100
      microg groups at 50 days old; however, no corpora lutea were observed in any rat
      in the 1000 mg group at age 50 days and at sacrifice. Observation of the whole
      mount specimens showed a low number of terminal end buds (TEBs) in the 1000
      microg group and a high number in the 10 microg group. It is suggested that
      neonatal administration of E2 affects the gonadotropin-secreting system,
      resulting in a decrease of progesterone, which is thought to influence the
      progression of mammary carcinomas induced by DMBA. Moreover, neonatal
      administration of E2 directly affects the mammary glands, and it is suggested
      that E2 may promote differentiation of TEBs resulting in inhibitory effects on
      the initiation of mammary carcinomas.

PMID- 16433027
TI  - Secretion of tumor-promoting and immune suppressive cytokines by cell lines of
      head and neck squamous cell carcinoma.
AB  - BACKGROUND: Cytokine profiles of permanent cell lines of head and neck squamous
      cell carcinoma (HNSCC) were analyzed to define the cytokine levels secreted in
      the absence of immune cells. MATERIALS AND METHODS: Cytokine profiles of IL-4, IL
      6, IL-8 and IL-10 were analyzed in the supematants of 4 different permanent HNSCC
      cell lines using the Bio-Plex human cytokine assay system. RESULTS: In HNSCC, IL
      6 and IL-8 are involved in oncogenic processes, while IL-4 and IL-10 suppress
      proper immune responses in the tumor microenvironment. Our data indicate that, in
      the absence of tumor-infiltrating immune cells, HNSCC secretes high levels of the
      proto-oncogenic cytokines IL-6 and IL-8, but no significant levels of the immune
      suppressors IL-4 and IL-10. CONCLUSION: The data strongly suggest that the
      intercellular crosstalk between cells of HNSCC and tumor-infiltrating immune
      cells in vivo is required to stimulate an increased production of immune
      suppressive mediators in head and neck cancer.

PMID- 16433028
TI  - Simulating soft data to make soft data applicable to simulation.
AB  - BACKGROUND: Biomedical processes are often influenced by measures considered "non
      crisp", "soft" or "subjective". Despite the growing awareness of the importance
      of such measures, they are rarely considered in biomedical simulation. This study
      introduces an input generator for soft data (input generator SD) that makes soft
      data applicable to simulation. MATERIALS AND METHODS: Machine learning approaches
      and standard regression techniques were applied to simulate odour intensity
      ratings. RESULTS: The performance of all the applied methods was satisfactory and
      the results can be used to modify systems biological mathematical models.
      CONCLUSION: Soft data should no longer be discounted in systems biological
      simulations. Exemplarily, it can be demonstrated that the input generator SD
      produces results that are similar to those that the simulated system can
      generate. Machine learning and/or appropriate conventional mathematical
      approaches may be applied to simulate noncrisp processes that can be used to
      modify mathematical models of any granularity.

PMID- 16433029
TI  - Doxorubicin-loaded calcium phosphate cement in the management of bone and soft
      tissue tumors.
AB  - Several materials have been used as drug delivery systems to maintain a high
      concentration of anticancer drugs at localized sites. The feasibility of using
      doxorubicin-loaded calcium phosphate cement (CPC) as a new material, which can
      release the drug as well as fill a postoperative bony defect, was investigated.
      The mechanical strength of cylinders of doxorubicin-loaded CPC was not lower than
      that of CPC alone. Culture medium incubated with doxorubicin-loaded CPC from 1 to
      7 days suppressed the proliferation of RMT-1 E4 rat breast cancer cells. In
      rabbits with doxorubicin-loaded CPC in their femurs, histological examinations
      showed diffuse edematous changes in the medullary space, but neither fracture nor
      skin necrosis occurred. Doxorubicin-loaded CPC markedly inhibited the
      proliferation of sarcoma 180 cells in the mouse air-pouch model. These results
      indicate that doxorubicin-loaded CPC may be useful in the local treatment of
      malignant bone and soft tissue tumors.

PMID- 16433030
TI  - A quantitative approach to the free radical interaction between alpha-tocopherol
      and the coantioxidants eugenol, resveratrol or ascorbate.
AB  - The regeneration of alpha-tocopherol (vitamin E; VE) by coantioxidants such as
      phenolics and ascorbate has been studied in homogeneous hydrocarbon solution and
      in biological systems. However, VE phenoxyl radicals (VE*) may be sufficiently
      reactive to cooxidize phenolic compounds and ascorbates. The coantioxidant
      behavior of some relevant phenols such as eugenol (EUG), isoeugenol (IsoEUG), 2,6
      di-tert-butyl-4-methoxyphenol (DTBMP), trans-resveratrol (RES) and L-ascorbyl-2,6
      dibutyrate (ASDB; an ascorbate derivative) with the antioxidant VE at a molar
      ratio of 1:1 was investigated by the induction period (IP) method in the kinetics
      of polymerization of methyl methacrylate (MMA) initiated by the thermal
      decomposition of 2,2'-azobis(isobutyronitrile) (AIBN; a source of alkyl radicals,
      R*) or benzoyl peroxide (BPO; a source of peroxy radicals, PhCOO*) under nearly
      anaerobic conditions. Synergism, implying regeneration of VE by the
      coantioxidant, was observed with only two of these combinations, VE/EUG with
      PhCOO* and VE/DTBMP with R*. For other mixtures of VE with a phenolic
      coantioxidant, VE was able to cooxidize the phenolic. Regeneration can only be
      observed if the bond dissociation energy (BDE) of the coantioxidant is lower
      than, or at least close to, that of VE. The driving force for regeneration of VE
      by EUG may be removal of the semiquinone radical of EUG by VE, leading to the
      formation of VE and EUG-quinonemethide, even though the BDE value of EUG is
      greater by 5.8 kcal/mol than that of VE. Further evidence for this mechanism of
      regeneration is provided by the value of approximately 2 for the stoichiometric
      factor (n) of EUG induced by PhCOO*, but not by R*, again implying the formation
      of EUG-quinonemethide. The regeneration of VE by DTBMP in the R* system may
      result from their much smaller difference in BDE (0.1-1.3 kcal/mol). Since VE is
      rapidly oxidized by PhCOO*, regeneration of VE by DTBMP was not found in this
      system. The observed IP for the VE/ASDB mixture in the R* system was much lower
      than that for VE alone, whereas the IP for VE/ASDB in the PhCOO* system was
      similar to that of VE. In the R* system, VE* was sufficiently reactive to
      cooxidize ASDB and, in addition, the prooxidation of VE may be promoted by the
      catalytic action of the ascorbate derivative. The present system, under nearly
      anaerobic conditions, is relatively biomimetic, since oxygen in living cells is
      sparse. Such studies could help to explain the mechanism of regeneration of VE by
      coantioxidants such as phenolic compounds and vitamin C in vivo.

PMID- 16433031
TI  - The role of Ca2+ in (-)-menthol-induced human promyelocytic leukemia HL-60 cell
      death.
AB  - A human promyelocytic leukemia HL-60 cell line was selected to examine the effect
      of (-)-Menthol on cell death. Based on the results from morphological changes and
      the percentage of viable cells in HL-60 cells after treatment with various
      concentrations of (-)-Menthol, it was shown that (-)-Menthol induced cell death
      through necrosis, not apoptosis. No cell cycle arrest was found in HL-60 cells
      examined by flow cytometry analysis. Also, the DNA gel electrophoresis method
      showed that (-)-Menthol did not induce apoptosis in HL-60 cells. However, it was
      found that (-)-Menthol induced the production of Ca2+ in these examined cells,
      dose-dependently. When HL-60 cells were pretreated with the chelator (BAPTA) of
      Ca2+ for 3 hours before addition of (-)-Menthol to the culture, a decrease of
      Ca2+ production was observed. Under the same conditions, the percentage of viable
      HL-60 cells was increased. Apparently Ca2+ production is associated with the
      induction of (-)-Menthol-induced cell death.

PMID- 16433032
TI  - mAgK114 suppresses lymphocyte infiltration into epidermis in the picryl chloride
      induced atopic dermatitis-like skin lesions of NC/Nga mice.
AB  - BACKGROUND: We have previously shown that when mouse AgK114 (mAgK114, a
      glycosylphosphatidylinositol anchored membrane-associated protein) is applied to
      the wound area, the inflammatory responses in the early recovery phase of damaged
      tissue are enhanced and wound closure is accelerated. This suggests that mAgK114
      has an important effect on skin wound repairing. MATERIALS AND METHODS: Whether
      mAgK114 supresses the development, in NC/Nga mice, of atopic dermatitis (AD)-like
      skin lesions induced by repeated application of 2,4,6-trinitrochlorobenzene
      (picryl chloride, PiCl) was examined under specific pathogen-free conditions.
      RESULTS: Histopathologically, the application of mAgK114-ointment to the PiCl
      treated NC/Nga mice remarkably suppressed severe lymphocytic infiltration into
      the epidermis, although total skin severity scores, histological changes in
      hypertrophy, erosion and infiltration of inflammatory cells into the corium and
      subcutaneous tissues were comparable between the mAgK114-treated group of mice
      and the control group. CONCLUSION: Our results suggest that mAgK114 would be
      beneficial for the treatment of atopic dermatitis by suppressing severe
      lymphocytic infiltration into the epidermis.

PMID- 16433033
TI  - Crude extract of garlic induced caspase-3 gene expression leading to apoptosis in
      human colon cancer cells.
AB  - Garlic (Allium sativum) is a popular spice, a remedy for a variety of ailments
      and is also known for its medicinal uses as an antibiotic, antithrombotic and
      antineoplastic agent. Epidemiological and animal studies have shown that garlic
      consumption reduces the incidence of cancer e.g. in the stomach, colon, breast
      and cervix. The aim of this study was to investigate whether garlic extract has
      any influence on caspase-3 activity and gene expression and on the signal
      induction of apoptosis in vitro. As an assay system, the flow cytometry assay,
      Western blotting and cDNA microarray were applied in human colon cancer colo 205
      cells. Our results indicated that garlic extract, when administered to the colo
      205 cell cultures, reduced the percetange of viable cells, induced apoptosis,
      increased the levels of Bax, cytochrome c and caspase-3, but decreased the level
      of Bcl-2. The results also showed that raw extract of garlic decreased the
      mitochondrial membrane potential and increased the caspase-3 activity and gene
      expression. We conclude that crude extract of garlic can induce apoptosis in colo
      205 cells through caspase -3 activity, by means of a mitochondrial-dependent
      mechanism.

PMID- 16433034
TI  - Pharmacokinetics and tissue penetration of a new carbapenem, doripenem,
      intravenously administered to laboratory animals.
AB  - The pharmacokinetic properties of doripenem following 20 mg/kg i.v. infusion were
      studied in various laboratory animals. The concentrations of doripenem in plasma,
      urine and tissue samples were determined by bioassay. Mean AUC0(0-infinityS)
      (microg x h/ml) and urinary recoveries (UR, %, 0-24 h) were 14.1 and 36.3 in
      mice, 9.3 and 42.1 in rats, 47.9 and 47.6 in rabbits, 78.6 and 83.1 in dogs and
      44.1 and 51.0 in monkeys, respectively. In monkeys, with co-administration of
      probenecid, the mean AUC(0-infinity) of doripenem increased about 2.2 times and
      urinary excretion was delayed slightly. In mice, the doripenem level was highest
      in the blood plasma, followed by the kidney, liver, lung, heart and spleen. These
      doripenem levels in various tissues rapidly decreased and no accumulation was
      observed. Serum protein binding rates (%) of doripenem were 25.2 in mice, 35.2 in
      rats, 11.8 in rabbits, 10.2 in dogs, 6.1 in monkeys and 8.1 in humans,
      respectively.

PMID- 16433035
TI  - Pronounced inhibitory effect of chlorcyclizine (CCZ) in experimental
      hepatocarcinoma.
AB  - Thepiperazine chlorcyclizine HCl (CCZ), possessing significant antimetabolic as
      well as virucidal and virustatic activities against the human immunodeficiency
      virus (HIV) and other retroviruses, was selected to determine its
      anticarcinogenic potential The anticancer activity of CCZ was evaluated against
      procarcinogen n-diethylnitrosamine (NDA)-initiated hepatocarcinogenesis, which
      was subsequently promoted by phenobarbital (PB) in male Sprague-Dawley rats. The
      anticancer efficacy of CCZ was monitored by estimating some potential markers of
      neoplastic and preneoplastic hepatic conditions, e.g., glutathione (GSH),
      glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase (gammaGTP). CCZ
      exhibited antineoplastic activity on a long-term therapeutic basis. Furthermore,
      this drug restricted the exponential increase of the antioxidant markers in the
      hyperplastic nodule and the surrounding liver tissues in comparison with the
      carcinogen-controlled rats during the entire period of treatment. A decrease in
      the number of nodules was observed in the CCZ-treated group.

PMID- 16433036
TI  - Enhancement of sodium fluoride-induced cell death by centrifugal force.
AB  - As an initial step in the study of the influence of orthodontic force on cellular
      function in vitro, the effects of centrifugal force on the cytotoxicity induced
      by various apoptosis inducers were investigated. When human oral squamous cell
      carcinoma (HSC-2) and human promyelocytic leukemia (HL-60) cell lines were
      treated with increasing magnitudes of centrifugal force (evaluated by g-value),
      the viability assessed by the MTT method and trypan blue dye exclusion began to
      decline. Centrifugal force enhanced the cytotoxicity of sodium fluoride (NaF),
      but not that of redox compounds (hydrogen peroxide, sodium ascorbate, gallic
      acid) or chemotherapeutic agents (daunorubicin, doxorubicin, idarubicin,
      mitoxantrone, peplomycin, 5-FU). The combination of NaF and centrifugal force
      enhanced caspase-3 activity. The present study suggests that centrifugal force is
      an additional factor that modifies the biological activity of NaF.

PMID- 16433038
TI  - Cytogenetic findings in adult greek myelodysplastic syndrome patients:
      predominance of single trisomy 8.
AB  - Myelodysplastic syndrome (MDS) is a clonal disorder of the pluripotent
      hematopoietic stem cells which is characterized by ineffective and dysplastic
      hematopoiesis. The pathogenesis of MDS is not well defined and it appears that
      multiple genetic changes are involved. Several studies have shown that certain
      chromosomal abnormalities may be influenced by environmental factors, while
      differences in the incidence of certain aberrations in different areas have also
      been reported. The aim of this study was to investigate the frequency and the
      type of chromosomal changes in Greek primary MDS patients. Single chromosomal
      abnormalities were focused on as possibly being primary changes implicated in the
      initiation of the neoplastic process. Using conventional cytogenetics, 239 MDS
      patients were studied and 63 cases were found with an abnormal karyotype
      (26.36%). Among the cytogenetically abnormal cases, 46 patients presented single
      chromosomal abnormalities (73.1%). These aberrations were according to frequency
      +8 (28.57), del(5q), -7/del(7q) and +14 (6.35 each), i(17q) and del(11(q13) (4.76
      each), +11, -Y, i(1q), del(8q), del(18p) and t(X;11) (1.59% each). In conclusion,
      the incidence of chromosomal abnormalities in Greek MDS patients was lower than
      that reported in the literature. The most common single anomaly was trisomy 8,
      while a relatively high incidence of an isolated +14 was also observed. Notably,
      this is the first time an isolated i(1q) has been described in the literature.

PMID- 16433037
TI  - Benzo[a]phenoxazines: a new group of potent P-glycoprotein inhibitors.
AB  - The ability of fifteen novel phenoxazine derivatives (four phenoxazines and
      eleven benzo[a]phenoxazines) to modulate multidrug resistance (MDR) in a P-gp
      overexpressing mouse T lymphoma cell line (L5178 MDR) was studied. A flow
      cytometric functional test, based on the differential accumulation of rhodamine
      123 by sensitive and multidrug-resistant cells, was employed. Seven
      benzo[a]phenoxazines were observed to increase the amount of rhodamine 123
      accumulated by resistant cells, i.e. to be new effective MDR modulators. The
      results allowed us to draw preliminary conclusions about the structural features
      of benzo[a]phenoxazines which are important for MDR modulation.

PMID- 16433039
TI  - Cinnamylidene ketones as potential modulators of multidrug resistance in mouse
      lymphoma and human colon cancer cell lines.
AB  - The resistance to chemotherapy of cancer cells is mediated by the overexpression
      of P-glycoprotein, as an ATP-dependent membrane efflux pump. Two families of
      compounds have been screened, the cinnamylidenecycloalkanones and
      cinnamylidenebenzocycloalkanones, as promising multidrug resistance (MDR)
      reversal agents on mouse lymphoma and human colon cancer (COL0320) cell lines.
      The antiproliferative effects of the cinnamylidene derivatives were tested with
      the MTT method The MDR effect on drug accumulation was tested by flow cytometry.
      Combinations of resistance modifiers and cytostatics were tested on the two cell
      lines to obtain evidence for additive or synergistic interactions. Verapamil was
      applied as a resistance-modifying positive control. The best effects in the
      reversal of MDR in both cell lines were exhibited by the methoxy derivatives 2-(2
      methaoxycinnamylidene)indan-1-one, 2-(2-methoxycinnamylidene)-3,4-dihydro-2H
      naphthalen-1-one, 6-(2-methoxycinnamylidene)-6,7,8,9-tetrahydrocyclohepten-5
      one), 2-cinnamylidene-3,4-dihydro-2H-naphthalen-1-one and 6-cinnamylidene-6,7,8,9
      tetrahydrobenzocyclohepten-5-one. 2-(2-methoxycinnamylidene) indan-1-one and 2-(2
      methoxy-cinnamylidene)-3,4-dihydro-2H-naphthalen-1-one were able to enhance the
      antiproliferative activity of doxorubicin in a synergistic way.

PMID- 16433040
TI  - Effects of indinavir in a preliminary phase I study on dogs with stage III slenic
      hemangiosarcoma.
AB  - HIV protease inhibitors are antiretroviral drugs able to prevent production of
      infectious particles. It has been shown that these protease inhibitors are able
      to inhibit cancer-promoted angiogenesis in patients affected by Kaposi's sarcoma.
      A preliminary phase I study on dogs with stage III splenic hemangiosarcoma was
      designed in order to evaluate the efficacy and toxicity of the protease inhibitor
      Indinavir to delay the progression of this advanced neoplasm. The results suggest
      that Indinavir is potentially beneficial in dogs affected by microscopic residual
      disease.

PMID- 16433042
TI  - Effect of SILA-409, a new organosilicon multidrug resistance modifier, on human
      pancreatic cancer xenografts.
AB  - BACKGROUND: Failure of cancer chemotherapy is largely caused by multidrug
      resistance in tumor cells, mediated by ABC transporters that pump many
      cytostatics out from the cells. Thus, inhibition of the activity of P
      glycoprotein efflux pumps can improve the therapeutic results. Disiloxanes are
      synthetic resistance modifiers that suppressed not only the multidrug resistance
      gene but also MRP in various cancer cell lines. Among these compounds, SILA-409
      [1,3-dimethyl-1,3-bis(4-fluorophenyl)-1, 3-bis(3-morpholino-propyl)
      disiloxanedihydro chloride] showed a remarkable antiproliferative effect and
      markedly inhibited the P-glycoprotein-mediated efflux mechanism in vitro. The
      efficacy of this organosilicon drug was investigated in vivo, in a xenograft
      system. MATERIALS AND METHODS: Human pancreatic cancer xenografts (PZX-40/19G)
      were treated s.c. with 10 mg/kg b.w. SILA-409 every second day for 34 days. Tumor
      volume changes were recorded every week. At the end of the experiment, a complete
      autopsy was performed and all the vital organs were evaluated histologically. The
      apoptotic and mitotic rates were counted and evaluated by morphometric methods,
      and the immunohistochemical expression of P-glycoprotein was determined using a
      monoclonal anti-p170 antibody. RESULTS: This large dose of the organosilicon
      compound did not result in histologically observable toxic effects, and some
      tumor growth delay was noted. SILA-409 did not affect the mitotic activity, but
      the number of apoptotic cells per mm2 was significantly increased. In the
      untreated tumors, 60% of the cells displayed p170-positivity, while in the
      treated group, P-glycoprotein was expressed in just 26% of the carcinoma cells.
      CONCLUSION: The multidrug reversal effect of SILA-409 was demonstrated in vivo
      without any apparent toxicity. In addition, it increased the apoptotic activity,
      exhibited some tumor growth delay, but did not affect the mitotic rate. This new
      organosilicon compound deserves further attention with a combination of multidrug
      resistant substrate chemotherapeutic agents, especially in multidrug-resistant
      tumors.

PMID- 16433041
TI  - Antitumor activity of doxorubicin encapsulated in hexadecylphosphocholine (HePC)
      liposomes against human xenografts on Scid mice.
AB  - Doxorubicin was encapsulated into liposomes composed of
      hexadecylphosphocholine:egg yolk phosphatidylcholine:stearylamine (HePC.EPC:SA)
      10:10.0.1 (molar ratio) (1) and EPC:SA 10:0.1 (molar ratio) (2). Liposomal
      formulations 1 and 2, as well as free doxorubicin and free HePC, were tested in
      vitro against HCT116 human colon cancer cell lines and peripheral blood
      mononuclear cells (PBMCs) obtained from healthy donors, using the sulphorodamine
      B assay. The activity of doxorubicin was retained or slightly improved when
      entrapped into liposomes 1 and 2, while liposomal formulation 1 incorporating
      doxorubicin was found to be less toxic against normal cells. The liposomes were
      tested in vivo against human colon cancer xenografts in scid mice. The antitumor
      activities of liposomes 1 and 2 were statistically similar to that of free
      doxorubicin, but their toxicity was significantly lower. Based on these results,
      the combination of HePC and doxorubicin in one liposomal formulation may be
      justified for further evaluation.

PMID- 16433043
TI  - Effect of the chalcone analog E,E-bis(2-hydroxybenzylidene) acetone on the 7,12
      dimethylbenz[a]anthracene-induced Ha-ras gene activity in vivo.
AB  - The chalcone analog E,E-bis(2-hydroxybenzylidene)acetone (HBA) was found to
      display strong NAD(P)H:quinone reductase (NQO1) inducer potency in Hepa 1c1c7
      cells. In order to determine whether this promising chemopreventive activity
      would extend to anticarcinogenic properties, the effect of HBA on the 7,12
      dimethylbenz[a]anthracene (DMBA)-induced expression of the Ha-ras gene in
      isolated RNA from liver, lung, kidney, spleen, thymus, lymph nodes and bone
      marrow of CBA/Ca inbred mice was investigated. DMBA is a well-known chemical
      carcinogen, which can act as initiator by causing point mutations in certain
      oncogenes and tumor suppressor genes. According to the previous results, elevated
      Ha-ras expression has been noted even 24 h after DMBA treatment. Administration
      of HBA simultaneously with DMBA resulted in a decrease of the DMBA-induced Ha-ras
      gene expression in all the investigated tissues. This observation suggests
      metabolic interaction of HBA and DMBA. Administration of HBA 24 h prior to the
      DMBA treatment reduced the Ha-ras gene expression in all the tissues but the
      liver, where a slight elevation could be detected. This latter effect could be
      the result of a possible CYPIA inducer and pro-oxidant effects of HBA. The pro
      oxidant effect of HBA can be taken into consideration based on its previously
      demonstrated GSH-reactivity and the present results obtained by investigation of
      the time-course of Fenton reaction-initiated degradation of 2-deoxyribose in the
      presence of HBA.

PMID- 16433044
TI  - The effects of emodin on the expression of cytokines and functions of leukocytes
      from Sprague-Dawley rats.
AB  - Emodin has been reported to induce apoptosis in many human cancer cell lines,
      although its effects on leukocyte functions in vitro have not been demonstrated
      Therefore, the purpose of this study was to assess the effect of emodin on the
      phagocytosis of macrophages, the activity of natural killer cells and the
      expression of cytokines in leukocytes from Sprague-Dawley rats. Leukocytes,
      isolated from rats, were placed into culture plates for incubation with or
      without various concentrations of emodin for 1-6 hours and the functions of
      macrophages and natural killer cells were evaluated by flow cytometric analysis.
      The results indicated that emodin caused a decrease in phagocytosis of
      macrophages after treatment for up to 4 hours but 6-hour treatments led to an
      increase in the phagocytosis of macrophages. Further, emodin increased the
      activity of natural killer cells, both effects being dose-dependent. The levels
      of cytokines from the examined leukocytes were evaluated by ELISA and the results
      indicated that emodin increased the levels of IL-1beta and TNF-alpha, results
      which were confirmed by PCR assay for the mRNA expressions of the examined
      cytokines.

PMID- 16433045
TI  - Cryosurgery for advanced malignant melanoma of the facial skin. A case report.
AB  - BACKGROUND: Cryosurgery is safely employed for the treatment of skin precancerous
      and malignant lesions of the head and neck in selected patients. The case of a
      101-year-old female patient with advanced malignant melanoma of the facial skin,
      undergoing cryosurgery, is reported in order to assess the feasibility and
      tolerability of the technique, as well as the biological implications of
      cryosurgical treatment in this specific neoplasm. CASE REPORT: A 101-year-old
      woman, with a large (pT4b N0 M0) cutaneous melanoma of the facial skin on the
      right cheek, was treated at the Division of Surgical Oncology of the National
      Cancer Research Institute, Italy, from June to August 2003. The treatment was
      accomplished by means of serial cryosurgical applications which were performed
      within three months; the bulk of the lesion was cryotreated with a liquid
      nitrogen cryoprobe, while the residual disease was treated with a nitrous
      protoxide cryoprobe, by means of the insertion technique. The treatment was well
      tolerated, with a good aesthetic result, and the patient is recurrence- and
      distant-disease-free two years after the initial cryosurgical application.
      CONCLUSION: Cryosurgery is feasible in the treatment of head and neck melanoma,
      mostly for mucosal melanomas and cutaneous lesions in anatomically critical
      sites, as well as in high-risk surgical patients. Here, a good aesthetic result
      was obtained in a very elderly patient with a large cutaneous melanoma of the
      facial skin, avoiding skin flap transposition for tissue repair and postoperative
      complications (e.g., serious bleeding or postoperative pain), with a satisfactory
      functional and oncological outcome at two years.

PMID- 16433046
TI  - Changes in maternal plasma levels of VEGF, bFGF, TGF-beta1, ET-1 and sKL during
      uncomplicated pregnancy, hypertensive pregnancy and gestational diabetes.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), transforming growth factor-beta1 (TGF-beta1), endothelin-1 (ET-1)
      and soluble c-kit ligand (sKL) are cytokines involved in embryogenesis. MATERIALS
      AND METHODS: Maternal plasma cytokines were measured with ELISA during the three
      trimesters of gestation and on the day of delivery in 93 pregnant women and 18
      age-matched non-pregnant control women. RESULTS: The VEGF and bFGF levels
      increased during the first trimester and declined thereafter, but they remained
      above the controls' values until delivery. The TGF-beta1 levels increased during
      the first trimester and remained unchanged thereafter. On the contrary, the ET-1
      levels decreased and remained low until delivery. VEGF, bFGF, TGF-beta1 and ET-1
      were increased in hypertensive pregnancy. Except for ET-1, these cytokines were
      also increased in gestational diabetes. No changes in plasma sKL were documented.
      CONCLUSION: All the aforementioned cytokines play a role in uncomplicated
      pregnancy, whereas hypertensive pregnancy is causatively-related with increased
      ET-1.

PMID- 16433047
TI  - An increase of CA 19.9 as the first clinical sign of ileocecal valve metastasis
      from breast cancer.
AB  - CASE REPORT: The case of a breast cancer patient with a progressive increase of
      CA 19.9 that indicated gastrointestinal metastasis is reported. After the
      observation of an increased CA 19.9 serum value (104.00; n.v. 0.0-37.00) a
      colonoscopy was performed. This examination showed the presence of an
      erythematous and granular zone near the ileocecal valve. Histological examination
      of biopsies taken during the colonoscopy revealed atypical monomorphic cells
      between the organoid pattern of the colon-type ducts. Immunohistochemical
      staining was positive for cytokeratin 7 and for estrogen receptors, consistent
      with metastatic epithelial malignancy. After eleven months, the patient presented
      with signs of intestinal obstruction, requiring an ileocolic bypass. At
      definitive histological examination, the tumor exhibited features of mammary
      metastases. CONCLUSION: This is the first report in the literature of an
      ileocecal valve metastasis from breast cancer diagnosed by an increase of CA
      19.9, which is a marker of primary colorectal carcinoma.

PMID- 16433048
TI  - Voriconazole curative treatment for Acremonium species keratitis developed in a
      patient with concomitant Staphylococcus aureus corneal infection: a case report.
AB  - The case of a 49-year-old male Caucasian, with more than a 3-year history of
      recurrent keratoconjunctivitis treated with steroids, antibiotics and midriatics,
      is reported. A combined Acremonium spp. and S. aureus infection was detected.
      After unsuccessful therapy with fluconazole, the Acremonium spp. infection was
      eradicated by voriconazole treatment. To our knowledge, this is the first case
      report of complete regression of this kind of infection by the use of
      voriconazole. Therefore, we strongly recommend, in the event of a compatible
      clinical picture, laboratory testing for mycetes even in the absence of traumatic
      events, and the use of the new generation azoles, in order avoid a keratoplasty
      intervention and disease progression to severe endophthalmitis.

PMID- 16433049
TI  - Whole-body MRI in comparison to skeletal scintigraphy in detection of skeletal
      metastases in patients with solid tumors.
AB  - AIM: To evaluate the diagnostic value of whole-body magnetic resonance imaging
      (MRI) and skeletal scintigraphy in the detection of skeletal metastases in
      patients with solid tumors. MATERIALS AND METHODS: One hundred and twenty-nine
      tumor patients were examined with whole-body MRI using coronal TIRM sequences for
      the different anatomical regions. Skeletal scintigraphy was performed with 99mTc
      DPD. RESULTS: In 105/129 (81%) patients, the whole-body MRI and skeletal
      scintigraphy findings were concordant. In 56/129 (43%) patients, both imaging
      modalities excluded skeletal metastases. In 49/129 (38%) patients, whole-body MRI
      and skeletal scintigraphy revealed metastases, however whole-body MRI
      demonstrated more extensive disease in 22/49 (45%) cases. In 6/49 (12%) cases,
      skeletal scintigraphy was superior to whole-body MRI in detecting more skeletal
      metastases. In 24/129 (19%) cases, the imaging findings were discordant. In 15
      cases, skeletal scintigraphy was negative, whereas whole-body MRI revealed
      skeletal metastases. In 9 cases, skeletal scintigraphy was positive, whereas
      whole-body MRI failed to detect these metastases. In 77/129 (60%) patients, whole
      body MRI revealed additional tumor-related findings. CONCLUSION: Whole-body MRI,
      as a new staging method, is superior to skeletal scintigraphy with respect to the
      detection of skeletal metastases and the extent of metastastic disease.
      Furthermore, whole-body MRI yields additional tumor-related findings. Therefore,
      whole-body MRI should be performed as an alternative to skeletal scintigraphy for
      the assessment of skeletal metastases.

PMID- 16433050
TI  - Mid-trimester fetal-placental velocimetry response to nifedipine may predict
      early the onset of pre-eclampsia.
AB  - The effect of nifedipine on fetal-placental blood flow at 22-24 weeks in patients
      with pregnancy-induced hypertension (PIH) was evaluated. Twenty patients with PIH
      were submitted to the Doppler evaluation of fetal-placental perfusion at 22-24
      weeks. The systo-diastolic (SID) ratio and the pulsatility index (PI) of uterine,
      umbilical and middle cerebral arteries and systemic blood pressure were recorded
      before and 7 days after nifedipine administration (10 mg/ per os 3 times/day
      until delivery). Statistical analysis was performed with paired and unpaired t
      test and the two-tailed Fisher exact test. Nifedipine significantly (p < 0.05)
      decreased the mean systolic pressure in all patients (from 146 to 135 mmHg): 8
      patients developed pre-eclampsia (PE) complicated by fetal growth restriction
      (FGR) (PE group), whilst the remaining were only affected by PIH (PIH group). The
      gestational age at delivery, neonatal birthweight and 1- and 5-min Apgar scores
      were significantly (p < 0.001) lower in PE than in PIH women. Nifedipine
      treatment significantly changed the PI and S/D ratio (mean +/- SEM) of the
      uterine (PI from 0.66 +/- 0.01 to 0.51 + 0.01; SID ratio: from 2.00 +/- 0.09 to
      1.79 + 0.05) and umbilical (PI: from 1.55 +/- 0.04 to 1.40 +/- 0.02; S/D ratio:
      from 2.45 +/- 0.09 to 2.31+/- 0.09) arteries and the middle cerebral PI (from
      1.45 +/- 0.03 to 1.61 +/- 0.01) artery only in PIH, but not in PE patients. Fetal
      placental blood flow changes after nifedipine may early identify patients at risk
      of PE.

PMID- 16433051
TI  - Factors influencing the presentation and outcome of tuberculous meningitis in
      childhood.
AB  - Tuberculosis (TB) is an important cause of morbidity and mortality worldwide.
      Here, we describe our experience of childhood tuberculous meningitis (TBM),
      focusing on factors influencing presentation and outcome. PATIENTS AND METHODS:
      Children aged 0-14 years, with diagnosis of TBM and 24 months of post-therapy
      follow-up, were evaluated in this retrospective study. RESULTS: Thirty-two
      patients with TBM were identified. Fever, nuchal rigidity and vomiting were the
      main presenting symptoms. Fourteen cases (44%) presented with cranial nerve
      palsy. Seventeen (53%) patients were in advanced stage of the disease on
      admission. Cerebrospinal fluid (CSF) examinations showed low glucose, high
      proteins and pleocytosis. A central nervous system device was placed in 4 cases
      (13%) because of worsening hydrocephalus. Four (13%) patients died, while 6 (19%)
      had sequelae. Faster normalization of CSF parameters was associated with better
      outcome. CONCLUSION: Early antimycobacterial therapy and close monitoring of TBM
      in childhood improve the outcome.

PMID- 16433052
TI  - Guest editorial: celebrating the 50TH anniversary of the introduction of
      chlorpromazine in North America and the advent of the psychopharmacology
      revolution.

PMID- 16433053
TI  - History of the discovery and clinical introduction of chlorpromazine.
AB  - BACKGROUND: The historical process of discovery and clinical introduction of
      chlorpromazine, one of the greatest advances of 20th century medicine and history
      of psychiatry, is analyzed. METHODS: In this review, we have studied the original
      works of pioneers in the discovery and clinical use of chlorpromazine, as well as
      the contributions of prestigious researchers (historians, pharmacologists,
      psychiatrists, etc.) about this topic. RESULTS: The discovery of phenothiazines,
      the first family of antipsychotic agents has its origin in the development of
      German dye industry, at the end of the 19th century (Graebe, Liebermann,
      Bernthsen). Up to 1940 they were employed as antiseptics, antihelminthics and
      antimalarials (Ehrlich, Schulemann, Gilman). Finally, in the context of research
      on antihistaminic substances in France after World War II (Bovet, Halpern,
      Ducrot) the chlorpromazine was synthesized at Rhone-Poulenc Laboratories
      (Charpentier, Courvoisier, Koetschet) in December 1950. Its introduction in
      anaesthesiology, in the antishock area (lytic cocktails) and "artificial
      hibernation" techniques, is reviewed (Laborit), and its further psychiatric
      clinical introduction in 1952, with initial discrepancies between the Parisian
      Val-de-Grace (Laborit, Hamon, Paraire) and Sainte-Anne (Delay, Deniker) hospital
      groups. The first North-American publications on chlorpromazine took place in
      1954 (Lehmann, Winkelman, Bower). The introduction of chlorpromazine in the USA
      (SKF) was more difficult due to their strong psychoanalytic tradition. The
      consolidation of the neuroleptic therapy took place in 1955, thanks to a series
      of scientific events, which confirmed the antipsychotic efficacy of the
      chlorpromazine. CONCLUSIONS: The discovery of the antipsychotic properties of
      chlorpromazine in the 1950s was a fundamental event for the practice of
      psychiatry and for the genesis of the so-called "psychopharmacological
      revolution."

PMID- 16433054
TI  - The haloperidol story.
AB  - Haloperidol was synthesized on the 11th of February 1958 at the Janssen
      Laboratories, in Belgium. Soon after its synthesis and animal studies, which
      suggested to Paul Janssen and his colleagues that this butyrophenone drug would
      be of great interest as its action was similar but much more powerful than that
      of chlorpromazine, haloperidol was administered to humans at the Liege hospital.
      The subsequent clinical studies confirmed that this new drug was particularly
      active against delusions and hallucinations. The introduction of haloperidol in
      the United States of America was difficult for clinical and legal reasons. For
      many years, haloperidol had been widely used in western countries, until the
      introduction of "new antipsychotics."

PMID- 16433055
TI  - Social context and health consequences of the antipsychotics introduction.
AB  - BACKGROUND: From the vantage point of fifty years after the introduction of
      antipsychotics to clinical practice, this article examines the social context and
      health consequences of their introduction. METHODS: Historical review of
      literature sources with commentary. CONCLUSIONS: The availability of
      antipsychotics over nearly half a century has powerfully influenced concepts of
      mental illness, dominant models of care versus control, health outcomes and side
      effect burdens. The large demand and economic success of antipsychotic
      medications is an important driver for research and development as well as
      sophistication in marketing. Regulatory agencies, funders and clinicians are
      faced with a moving target as indications for use of antipsychotics move well
      beyond the traditional core of schizophrenia and acute mania into depression,
      anxiety, behavioral disturbance with dementia and some forms of personality
      disturbance. The history of antipsychotics and mental illness is arguably being
      written as forcefully now, in an environment of rapid scientific change, as was
      the case in the 1960s era of rapid social change when chlorpromazine prompted a
      shift of emphasis from asylum to community. Psychosis is a challenge to how we
      interpret and approach our inner experiences and societal structures.
      Accordingly, it is not surprising that the history of antipsychotic drugs
      resonates with a lively interplay of social, health and economic issues and an
      ongoing quest to comprehend mental phenomena and their variants.

PMID- 16433056
TI  - U.S. national trends in the use of antipsychotics during office visits, 1998
      2002.
AB  - BACKGROUND: There is a paucity of studies on U.S. national trends in the use of
      antipsychotic medications in the 21st century. This study examined national
      trends in the prescribing of antipsychotic drugs in office-based physician
      practices. METHODS: National probability sample survey data from 1998-2002
      National Ambulatory Medical Surveys were used to analyze the prescribing trends.
      The weighted visit estimates and percentages were compared across the years using
      z-test. RESULTS: The number of antipsychotic-related visits was found to increase
      significantly and nearly two-fold, from 4.6 million in 1998 to 8.6 million in
      2002. During the same period, the number of visits for second-generation
      antipsychotic drugs nearly tripled. The proportion of visits for the second
      generation agents, as a percentage of visits for all antipsychotic drugs, rose
      sharply from about 48% in 1998 to 84% in 2002. Correspondingly, the percentage of
      visits involving first-generation antipsychotic drugs declined. The growth in the
      number of visits involving antipsychotic drugs over the 5-year period was
      substantial (120%) in visits with non-psychiatrist physicians, but not in visits
      involving psychiatrists. CONCLUSIONS: The trend of growth in prescription of
      antipsychotic drugs in office visits, accounted by increased use of second
      generation antipsychotics, has persisted into the 21st century. Increased
      prescribing of these agents by non-psychiatrists is also apparently fueling this
      trend. This trend of shift from first-to-second generation antipsychotic agents,
      though not unambiguously supported by extant safety and efficacy data, is
      endorsed by guidelines based on expert-consensus and limited data. Given the high
      level use of second-generation drugs, more practical studies of these drugs,
      focusing on effectiveness or long-term outcomes, are needed.

PMID- 16433057
TI  - Low frequency rTMS stimulation of the right frontal cortex is as effective as
      high frequency rTMS stimulation of the left frontal cortex for antidepressant
      free, treatment-resistant depressed patients.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising
      relatively non-invasive alternative for the treatment of depression. The purpose
      of this study was to compare the apparent effectiveness of high frequency (20
      Hertz) rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) with
      that of low frequency (1 Hz) rTMS applied over the right DLPFC METHODS: Twenty
      eight antidepressant-free adults with major depressive (n = 25) or bipolar (n =
      3) disorder (not on mood stabilizers) in a current major depression (Hamilton
      Rating Scale for Depression [HAM-D-21] > or = 18; Mean = 24.5, SD = 5.51) were
      treated (14 right, 14 left) for 4 weeks. RESULTS: Overall paired t-tests revealed
      a significant reduction in mean HAM-D-21, Beck Depression Inventory (BDI-II), and
      Clinical Global Impression of Change (CGIC) scores at the end of treatment for
      both groups (high frequency left DLPFC and low frequency right DLPFC). The
      treatment response rate found (32%) was typical of other response rates reported
      in the literature (6,30). One-month follow-up data was obtained from 50% of
      participants. At 1-month follow-up no significant differences were noted as
      compared to patients' performance at last treatment visit, indicating moderate
      robustness of rTMS treatment over time. Furthermore, magnetic stimulation did not
      substantially alter patient memory over the course of treatment. CONCLUSION: rTMS
      given at low frequency over the right frontal cortex appears to be as effective
      treatment of refractory depression as high frequency treatment over the left
      frontal cortex.

PMID- 16433058
TI  - A description of next-step switching versus augmentation practices for
      outpatients with treatment-resistant major depressive disorder enrolled in an
      academic specialty clinic.
AB  - BACKGROUND: There is a paucity of naturalistic studies from depression specialty
      clinics describing the next-step (augmentation versus switching) practices of
      clinicians for outpatients with major depressive disorder (MDD) resistant to an
      antidepressant trial of adequate dose and duration. METHODS: Eighty-five MDD
      outpatients enrolled in one of two specialty clinics, who had not achieved
      remission after a first adequate prospective antidepressant trial conducted at
      the clinic underwent either augmentation (n = 36) or switching (n=49) of their
      antidepressant regimen. Outcome was defined with the use of the Clinical Global
      Impressions (CGI) Scale. RESULTS: Nonresponders (CGI-I>3) following the first
      antidepressant trial were more likely to have their treatment switched than
      patients who experienced incomplete response (CGI-I<4, CGI-S>1) (67.2% versus
      28.5%, p = 0.001). Incomplete responders during the first trial who went on to
      receive augmentation had higher remission rates (60.0% versus 0%, p=0.01), lower
      endpoint depression severity scores (1.8 +/- 1.1 versus 3.3 +/- 0.8, p = 0.01)
      and greater clinical improvement scores (1.6 +/- 1.1 versus 3.0 +/- 0.0, p=0.03)
      than incomplete responders who had their antidepressant regimen switched.
      Although nonresponders to the first treatment who were switched experienced
      greater symptom improvement than nonresponders who were augmented (2.7 +/- 1.1
      versus 3.4 +/- 1.2, p=0.03), there was no significant difference (p>0.05) between
      these two groups with respect to remission rates (18.6% versus 14.2%,
      respectively) and endpoint depressive severity (3.0 +/- 1.4 versus 3.4 +/- 1.4,
      respectively). CONCLUSIONS: In this nonrandomized, naturalistic treatment
      setting, nonresponders to an adequate, prospective antidepressant trial were more
      likely to have their antidepressant regimen switched, while patients with
      incomplete response during the first trial were more likely to have their regimen
      augmented. In addition, patients with incomplete response who had their treatment
      augmented had better outcome than patients with incomplete response who had their
      treatment switched.

PMID- 16433059
TI  - An open-label study of tiagabine as augmentation therapy for anxiety.
AB  - BACKGROUND: At least 50% of patients with anxiety disorders experience only
      partial response to pharmacotherapy and require augmentation therapy. Gamma
      aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS, and
      agents that modulate GABA neurotransmission have shown promise in the treatment
      of anxiety disorders and are often used as augmentation agents. OBJECTIVE: This
      study evaluated tiagabine, a selective GABA reuptake inhibitor (SGRI), as
      augmentation therapy. METHODS: This 8-week, open-label study enrolled patients
      who remained symptomatic despite adequate drug trials for treatment of anxiety
      symptoms. Tiagabine augmentation therapy was initiated at 4 mg/d (taken in 2
      doses; one in the morning with breakfast and one in the evening with a snack) for
      2 days and increased to 8 mg/d for 10 days. Dose was then adjusted according to
      efficacy/tolerability in increments of 2 mg every 3 days up to a maximum of 20
      mg/d. Effect was assessed using the Hamilton Rating Scale for Anxiety (HAM-A),
      Beck Anxiety Inventory (BAI), Clinical Global Impression (CGI) scale, Pittsburgh
      Sleep Quality Index (PSQI), and 36-item Short-Form Health Survey (SF-36).
      RESULTS: Of the 18 patients enrolled, 17 were included in the efficacy analysis;
      one withdrew due to an adverse event prior to post-baseline assessment. Mean
      final dose of tiagabine was 13 mg/d. Tiagabine as augmentation therapy further
      reduced anxiety symptoms, as shown by significant decreases in mean HAM-A total
      and BAI scores at Week 8 (P<0.001). Thirteen patients (76%) responded (> or =50%
      reduction in HAM-A total score), and 10 patients (59%) achieved remission (HAM-A
      total score < or =7) at Week 8. Tiagabine improved sleep quality, with a
      significant reduction seen in PSQI global score at Week 8 (P=.001). Augmentation
      therapy with tiagabine was generally well tolerated. CONCLUSION: These
      preliminary findings suggest that the SGRI tiagabine may be an effective and
      generally well tolerated augmentation therapy in patients with anxiety who remain
      symptomatic despite adequate drug trials for treatment of anxiety symptoms.

PMID- 16433060
TI  - Suicide among patients with schizophrenia: a consideration of risk and protective
      factors.
AB  - BACKGROUND: The elevated rate of suicide among patients with schizophrenia is
      well documented and thus frequently researched. The majority of research has
      focused solely on the identification of risk factors that predispose patients to
      attempt or commit suicide. This review serves to expand on the literature
      pertaining to suicide risk factors by additionally outlining how protective
      factors may shield against suicide within this unique patient population.
      METHODS: A literature review of English-language publications pertaining to
      suicide among people with schizophrenia was completed using PsychINFO and MEDLINE
      databases between the years of 1960-2004 and 1950-2004 respectively. Special
      emphasis was given to studies of risk factors and protective factors for suicide.
      RESULTS: Commonly supported risk factors for suicide were identified: previous
      attempts, severity of illness, comorbidity, social isolation, temporal
      relationships, and demographic characteristics. Risk factors such as a history of
      violence, the presence of command hallucinations, and recent tragic loss were
      found to warrant future study. Social support, positive coping skills, life
      satisfaction, and resiliency emerged as protective factors that may mitigate
      suicide. CONCLUSIONS: Understanding why some patients wish to end their lives but
      also why some desire to live allows for more comprehensive suicide prevention.

PMID- 16433061
TI  - Empirical evidence for a State personality group.

PMID- 16433062
TI  - Vesicular and non-vesicular glutamate release in the nucleus accumbens in
      conditions of a forced change of behavioral strategy.
AB  - Studies on Sprague-Dawley rats used intracerebral dialysis and high-performance
      liquid chromatography to identify sources of glutamate release into the
      intercellular space of the nucleus accumbens during forced correction of food
      related behavior, i.e., on presentation to the feeding rat of a conditioned
      signal previously combined with a pain stimulus or on replacement of a food
      reinforcement with an inedible food substitute. The results showed that glutamate
      release observed in the nucleus accumbens during these tests can be prevented by
      tetrodotoxin (1 microM), which blocks exocytosis, but not by (S)-4
      carboxyphenylglycine (5 microM), which blocks non-vesicular glutamate release.
      Conversely, administration of (S)-4-carboxyphenylglycine halved baseline
      glutamate release, while administration of tetrodotoxin had no effect on this
      process. These data provide evidence that different mechanisms control glutamate
      release into the intercellular space of this nucleus in baseline conditions and
      in conditions of evoked correction of feeding behavior: the source of baseline
      glutamate release is non-vesicular glutamate release, while glutamate release
      seen during forced correction of feeding behavior results from increases in
      synaptic release.

PMID- 16433063
TI  - Metabolism and receptor binding of serotonin in brain structures during
      performance of a conditioned passive avoidance response.
AB  - The levels of serotonin and its metabolite 5-hydroxyindoleacetic acid, monoamine
      oxidase activity, and the specific binding of the radioligand [3H]serotonin were
      measured in the prefrontal cortex, striatum, amygdaloid complex, hippocampus, and
      periacqueductal gray matter of the midbrain in rats at different time points
      after training to a conditioned passive avoidance reaction. Changes in
      serotoninergic activity were found to be characteristic only for the process of
      reproducing the conditioned reaction. The metabolism and serotonin receptor
      binding in these brain structures did not change immediately after the training
      period or one day after this, or in conditions of failure to reproduce the
      reaction because of amnesia, or in untrained animals. The involvement of the
      brain serotoninergic system in the process of performing the conditioned reaction
      was found to demonstrate a spatial-structural selectivity: the metabolism and
      receptor binding of serotonin changed in the amygdaloid complex, periacqueductal
      gray matter, and the striatum, while no changes were seen in the hippocampus or
      prefrontal cortex. All three brain structures showed decreases in [3H]serotonin
      receptor binding of. Serotonin levels did not change, though the amygdaloid
      complex and periacqueductal gray matter showed increases in oxidative deamination
      of serotonin and increases in the active transport of the metabolite, while the
      striatum showed decreases in serotonin catabolism. The differences in the
      catabolism of this neurotransmitter suggest that the decrease in serotonin
      receptor binding in these brain structures depends on different synaptic
      processes--presynaptic in the striatum and postsynaptic in the amygdaloid complex
      and periacqueductal gray matter. It is concluded that the decrease in the
      functional activity of serotoninergic transmission in the amygdaloid complex and
      periacqueductal gray matter is one of the mechanisms involved in activation of
      the emotiogenic system triggering the process of reproduction of the memory
      trace.

PMID- 16433064
TI  - Studies of the synaptic plasticity of field CA3 of the hippocampus during
      tetanization of the perforant path.
AB  - Studies on living slices of hippocampus-entorhinal cortex formation from adult
      rats were performed to investigate changes in responses in field CA3 to
      stimulation of mossy fibers in conditions of perforant path tetanization with
      different parameters. Tetanization of the perforant path at frequencies of 10 and
      100 Hz induced depression of responses in CA3 on testing of this same path.
      Tetanization of the perforant path at a frequency of 10 Hz and an amplitude
      subthreshold for potentiating mossy fiber synapses in CA3 became threshold if
      preceded by tetanization of the perforant path at a frequency of 100 Hz.
      Tetanization of mossy fibers at 10 Hz resulted in potentiation of the input to
      CA3, while tetanization at 100 Hz induced depression. High-frequency tetanization
      of the perforant path (100 Hz) delivered in trains following at the frequency of
      the theta rhythm, led mainly to depression of field CA3 responses to stimulation
      of mossy fibers.

PMID- 16433065
TI  - Inositol triphosphate and ryanodine receptors in the control of the
      cholinosensitivity of common snail neurons by the Na,K pump during habituation.
AB  - The effects of the Na,K pump inhibitor ouabain on habituation of the common snail
      to tactile stimulation were identical to the ouabain-induced modification of the
      decrease in the cholinosensitivity of defensive behavior command neurons in the
      common snail in a cellular model of habituation. Studies addressed the effects of
      intracellularly delivered ligands of two types of Ca2+ depot receptors--inositol
      triphosphate (IP3) receptors and ryanodine receptors--on the action of ouabain in
      the cellular analog of habituation. The IP3 receptor antagonist heparin (0.1 mM),
      the IP3 receptor agonist inositol triphosphate (0.1 mM), and the ryanodine
      dependent Ca2+ mobilization inhibitor dantrolene (0.1 mM) prevented ouabain from
      modifying the depression of the evoked acetylcholine current. The ryanodine
      agonist/antagonist ryanodine was used at two concentrations (0.1 and 1 mM) and
      neither had any effect on the action of ouabain. It is concluded that Ca2+
      mobilized from intracellular Ca2+ depots via IP3 receptors is involved in the
      neuronal mechanism of regulation of the habitation of the common snail to tactile
      stimulation by the Na,K pump.

PMID- 16433066
TI  - Functional electrostimulation of muscles as a method for restoring motor
      functions.
AB  - The main functions of a method of functional electrical stimulation of muscles
      (FES) are described: diagnostic, prognostic, and therapeutic. The main indication
      for using the FES method is a deficiency of muscle function, which may be organic
      (due to lesions to neuromuscular structures) or functional (associated with
      relaxation of the muscular apparatus). The five most significant functions of the
      FES method were established: 1) identification of correctable movements and
      stimulable muscles; 2) identification of the amplitude and time program for
      stimulation; 3) stimulation regimes for pathological gaits; 4) stimulation
      parameters; 5) positioning of skin electrodes on the human body. Using the
      example of two severe central nervous system pathologies (spinal cord lesions in
      the lumbosacral area and hemiparesis of cerebral origin), the positive effects of
      FES on the process of motor rehabilitation of this category of patients were
      demonstrated.

PMID- 16433067
TI  - Electroconvulsive shock induces neuron death in the mouse hippocampus:
      correlation of neurodegeneration with convulsive activity.
AB  - The relationship between convulsive activity evoked by repeated electric shocks
      and structural changes in the hippocampus of Balb/C mice was studied. Brains were
      fixed two and seven days after the completion of electric shocks, and sections
      were stained by the Nissl method and immunohistochemically for apoptotic nuclei
      (the TUNEL method). In addition, the activity of caspase-3, the key enzyme of
      apoptosis, was measured in brain areas immediately after completion of electric
      shocks. The number of neurons decreased significantly in field CA1 and the
      dentate fascia, but not in hippocampal field CA3. The numbers of cells in CA1 and
      CA3 were inversely correlated with the intensity of convulsions. Signs of
      apoptotic neuron death were not seen, while caspase-3 activity was significantly
      decreased in the hippocampus after electric shocks. These data support the notion
      that functional changes affect neurons after electric shock and deepen our
      understanding of this view, providing direct evidence that there are moderate (up
      to 10%) but significant levels of neuron death in defined areas of the
      hippocampus. Inverse correlations of the numbers of cells with the extent of
      convulsive activity suggest that the main cause of neuron death is convulsions
      evoked by electric shocks.

PMID- 16433069
TI  - Interaction of neurons at the level of cell bodies in the snail CNS.
      Heterogeneity of the neuroactive environment.
AB  - Experiments on the CNS of snail Lymnaea stagnalis in which a cell isolated from
      the serotonin cluster PeA was used as a mobile sensor neuron demonstrated the
      presence of neuroactive factors at the surface of the cellular "cortex" of the
      pedal ganglion. Apart from the previously known factor serotonin, effective
      concentrations of a factor suppressing the electrical activity of PeA were found
      at this site, along with a depolarizing factor which, unlike serotonin, narrowed
      PeA action potentials. The ability of these factors to control the electrical
      activity of the sensor neuron demonstrates the possible involvement of chemical
      agents in the intercellular space of the "cortex" in neuronal signaling.

PMID- 16433068
TI  - Changes in the latency of mouse inferior colliculus neuron responses depending on
      the position and direction of movement of spectral contrast.
AB  - Changes in the latency of mouse (Mus musculus) inferior colliculus neuron
      responses in the presence of wideband sound signals with spectral notches and
      noise bands with regularly varying central notch/band frequencies were studied.
      Relationships between the latency and the magnitude of the response on the one
      hand and the central notch/band frequency on the other were obtained (latency and
      spike count functions). Crossing of the margins of the excitatory areas of the
      responses of the frequency receptive fields of neurons by spectral notches/noise
      bands could lead to displacement of latency functions (and corresponding
      displacements in spike count functions). Direction-dependent shifts in latency
      and spike count functions were more characteristic of primary-like and V-shaped
      neurons. The most interesting feature of the directional sensitivity of
      inhibition-dependent neurons was the selective decrease in the latency and
      selective synchronization of the initial spike response (with a corresponding
      increase in the spike count). The dynamic properties of inhibition-dependent
      neurons can be explained on the basis of their selective sensitivity to the
      position of the spectral contrast in the frequency receptive field, which is
      associated with disinhibition, and by the nature of the distribution of the
      excitatory and inhibitory inputs. The extents of these effects depended on the
      spectral shape of the signals and the widths of the spectral notches.

PMID- 16433070
TI  - The role of the flabellar and ellipsoid bodies of the central complex of the
      brain of Drosophila melanogaster in the control of courtship behavior and
      communicative sound production in males.
AB  - The role of flabellar and ellipsoid bodies of the central complex of the brain of
      Drosophila melanogaster males in controlling courtship behavior and the
      accompanying sound production was studied by comparative analysis of the
      characteristics of courtship and singing in wild-type flies and individuals of
      five mutant lines with different anatomical defects in these parts of the brain.
      Investigations were performed using the following fly lines: Canton S (wild-type,
      controls), ebo(KS263), with defects only in the ellipsoid bodies, and ebo(1041),
      ceb(849), ceb(892), and cba(KS96), with different levels of abnormality in both
      parts of the central complex. The data obtained here indicated that the flabellar
      and ellipsoid bodies are involved in: 1) maintaining a high level of courtship
      activity; 2) regulating the precision of male movements while following females;
      3) in controlling the nature and stability of the sound elements from which
      communicative signals are constructed; 4) in regulating the rhythmic structure of
      signals dependent on the stability of pacemakers function; 5) establishing the
      relationship between behavior and the context in which it occurs.

PMID- 16433071
TI  - The roles of nitric oxide and carbon dioxide gas in the neurotoxic actions of
      oxygen under pressure.
AB  - The hypothesis that in conditions of hyperbaric oxygenation, nitric oxide (NO)
      modulates the vasodilatory effect of CO2 in the brain and thus accelerates the
      neurotoxic action of oxygen was verified experimentally. Conscious rats breathed
      atmospheric air or oxygen at 5 atm and blood flow in the striatum was measured
      before and after inhibition of carbonic anhydrase with acetazolamide, which
      causes retention of CO2 in the brain. Acetazolamide (35 mg/kg) increased blood
      flow in the animals when breathing air by 38 +/- 7.4% (p < 0.01), while
      preliminary inhibition of NO synthase with N(omega)-nitro-L-arginine-methyl ester
      (L-NAME, 30 mg/kg) significantly weakened its vasodilatory action. Inhibition of
      carbonic anhydrase in animals breathing hyperbaric oxygen at 5 atm prevented
      cerebral vasoconstriction, increased brain blood flow, and accelerated the
      development of oxygen convulsions. The vasodilatory effect of acetazolamide in
      hyperbaric oxygenation was significantly reduced in animals pretreated with the
      NO synthase inhibitor, such that the latent period of convulsions increased. The
      results obtained here provide evidence that in conditions of extreme hyperoxia,
      NO modulates the cerebral hyperemia developing in conditions of CO2 retention in
      the brain and accelerates the development of the neurotoxic actions of hyperbaric
      oxygen.

PMID- 16433072
TI  - Inactivation of C/EBP transcription factors specifically affects the synaptic
      plasticity of a common snail neuron.
AB  - Our previous studies showed that the acquisition of nociceptive sensitization in
      common snails is accompanied by long-term facilitation of synaptic transmission
      in defensive behavior command neuron LP11, this being dependent on translation
      and transcription processes. The characteristics of the neurochemical mechanisms
      of plasticity in the different sensory inputs of this nerve cell were identified.
      The mechanisms of induction of synaptic facilitation of the responses of neuron
      LP11 to chemical sensory stimulation of the snail's head involved NMDA glutamate
      receptors, serotonin receptors, cAMP, and serotonin-modulated transcription
      regulating protein SMP-69. The mechanisms of induction of synaptic facilitation
      of another sensory input of the neuron--from tactile receptors on the head -
      involved protein kinase C. The present study addresses the involvement of C/EBP
      transcription factors (CCAAT-enhancer-binding protein) in the processes of
      synapse-specific plasticity of neuron LP11 during the acquisition of
      sensitization in snails. C/EBP was inactivated using oligonucleotides
      specifically binding to these proteins. The results showed that acquisition of
      sensitization during intracellular administration of oligonucleotides led to the
      selective suppression of synaptic facilitation in the responses of neuron LP11 to
      chemical sensory stimulation of the snail's head. Synaptic facilitation in the
      responses to tactile stimulation of the head or foot developed as in neurons in
      control sensitized snails. It is suggested that C/EBP transcription factor is
      selectively involved in the mechanisms of synapse-specific plasticity of the
      sensory input of neuron LP11 from chemoreceptors on the head during the
      acquisition of sensitization in snails.

PMID- 16433073
TI  - Effects of experimental increases and decreases in thyroxine levels on the extent
      of cataleptic freezing reactions in rats.
AB  - Numerous clinical observations have provided evidence for a tight connection
      between impairments in the functions of the hypothalamo-hypophyseal-thyroid
      system and nervous and mental disorders. The aim of the present work was to
      compare the effects of experimental decreases and increases in blood thyroxine
      levels on the extents of two types of pathological freezing reaction in male
      Wistar rats--spontaneous catalepsy and catalepsy evoked by pinches at the nape of
      the neck (pinch-induced catalepsy). Chronic administration of the thyroxine
      synthesis inhibitor propylthiouracil (5 mg/kg/day for 28 days) significantly
      decreased the blood hormone level and sharply increased the proportion of animals
      showing spontaneous catalepsy and the immobility time, but had no effect on the
      extent of pinch-induced catalepsy. At the same time, chronic administration of
      thyroxine (0.1 mg/kg/day for 28 days), which produced significant increases in
      blood hormone levels, had no effect on the extent of spontaneous catalepsy but
      significantly increased the proportion of animals showing pinch-induced catalepsy
      and the duration of this type of catalepsy. It is concluded that both
      insufficiency and excess of thyroid hormones have cataleptogenic actions, but
      enhance different types of catalepsy.

PMID- 16433075
TI  - Orthodontic practices in Australasia: practice activity.
AB  - OBJECTIVE: To collect baseline data on practice types and services provided by
      orthodontists in Australia and New Zealand. METHOD: A total of 510 questionnaires
      was sent and 258 were returned. The response rate was 53 per cent. RESULTS: The
      average age of respondents was 50 years (SD: 9.8 years) with female orthodontists
      being younger (Mean: 42.3 years; SD: 6.5). The ratio of responding female to male
      orthodontists was 1:8.8. Overall, more orthodontists were in solo private
      practice than associateships or partnerships. New Zealand orthodontists were more
      likely to be in associateships. Australian orthodontists had twice the number of
      practices (Mean: 2.4; SD: 1.4) than their New Zealand counterparts (Mean: 1.1;
      SD: 0.3). Orthodontists estimated they saw a mean of 21.3 (SD: 11.3) patients per
      day. Older orthodontists saw few patients in a day and spent fewer hours in any
      practice activity in a week. The mean waiting time for a consultation appointment
      in the private sector in New Zealand was nearly twice that in Australia. There
      was a significant association between male orthodontists and referral of patients
      by general dental practitioners. More than three quarters of respondents
      incorporated retention fees into the treatment fee. Overall, orthodontists were
      satisfied with the workload and did not want more orthodontists in their
      geographical area. CONCLUSION: This study provides a sound basis for
      consideration of challenges in practice and changes over time.

PMID- 16433074
TI  - Effects of active transport of 5-hydroxyindoleacetic acid on measures of
      serotonin metabolism in the brain.

PMID- 16433076
TI  - An orthodontic information package designed to increase patient awareness.
AB  - BACKGROUND: Most patients and their parents experience difficulty in fully
      appreciating the implications and demands of orthodontic treatment. This is
      largely because of inadequate understanding of the process of treatment or the
      commitment required. OBJECTIVES: To determine if a specifically developed video
      information package could significantly increase patient awareness of the
      implications of a full course of orthodontic treatment. Changes in attitude to
      orthodontic treatment after viewing the package were also measured. METHODS: Year
      7 (12 year-old) students in two primary schools in the City of Gold Coast,
      Australia were randomly allocated to either a study group or a control group.
      Knowledge of and attitude to orthodontic treatment were measured with self
      administered questionnaires before and after viewing the information package.
      RESULTS: The intervention group showed a 15 per cent gain in knowledge (p <
      0.001). There was no gain in knowledge for the 45 students in the control group.
      There was no measured change in perception of need for orthodontic treatment in
      the study group. There was, however, an increase in potential compliance and
      positive attitude to the appearance of orthodontic appliances. There was a small
      increase in willingness to undertake treatment, but this was not statistically
      significant. CONCLUSIONS: The information package developed for this study
      increased awareness of the implications and practical difficulties which may be
      encountered during a course of orthodontic treatment, and produced some changes
      in attitude to treatment.

PMID- 16433078
TI  - Prediction of treatment outcome following correction of anterior crossbites in
      the mixed dentition: orthodontic versus orthopaedic methods.
AB  - AIM: To separate subjects with anterior crossbite and mild maxillary deficiency
      into two groups: those that can be treated successfully with a 2 x 4 appliance
      and those that should be treated with reverse headgear and maxillary expansion.
      METHODS: Thirty mixed dentition subjects each with an anterior crossbite, a
      concave profile, a deficient maxilla, and an ANB angle between -2 and +1 degrees
      were used. Fifteen subjects (8 boys, 7 girls; Mean age: 9.17 +/- 1.1 years) were
      successfully treated with a 2 x 4 appliance (orthodontic treatment group) and
      remainder (5 boys, 10 girls; Mean age: 8.6 +/- 1.5 years) were successfully
      treated with reverse headgear and maxillary expansion after initial treatment
      with a 2 x 4 appliance had failed (orthopaedic treatment group). Unstandardised
      discriminant function coefficients and a constant were calculated for selected
      pretreatment cephalometric variables. RESULTS: The NSAr angle was significantly
      smaller (p < 0.01) and both anterior and posterior cranial base lengths were
      significantly longer in the orthodontic treatment group (p < 0.001) compared with
      the orthopaedic group. The prediction index developed was: (PI) = -0.2 NSAr +
      0.243 S-N + 0.187 S-Ar + 3.366. The critical score was 0. With positive scores a
      2 x 4 appliance can be used and with negative scores reverse headgear and
      expansion are indicated. CONCLUSION: An equation able to predict treatment
      success with either a 2 x 4 appliance or reverse headgear has been developed.

PMID- 16433077
TI  - Comparison of the bond strength of stainless steel orthodontic brackets bonded to
      crown porcelains.
AB  - BACKGROUND: The bond strengths and mode of failure of stainless steel orthodontic
      brackets bonded to the newer all-ceramic crown systems has not been fully
      investigated. OBJECTIVES: To compare the shear-peel bond strengths and modes of
      failure of stainless steel Begg orthodontic brackets bonded to all-ceramic crown
      systems (Finesse, Empress II) and a conventional feldsphatic crown porcelain
      (Vita Omega 900). METHODS: Fifteen flat-surface discs of three crown porcelains
      (Finesse, Vita Omega 900, Empress II) were made and mounted in acrylic moulds.
      The discs were pumiced, etched with phosphoric acid, primed with silane, and a
      flat stainless steel Begg bracket bonded to each disc with a chemical cure
      composite resin (Unite Bond). The discs were stored for one week in water and
      debonded with a sheer-peel load in an Instron uniaxial testing system with a
      crosshead speed of 0.5 mm/min. The composite remnants on the ceramic surfaces
      were classified using the Adhesive Remnant Index (ARI). RESULTS: The bond
      strength of Finesse (15.03 +/- 1.90 MPa) was significantly greater (p < 0.001)
      than Vita Omega 900 11.51 +/- 2.35 MPa) and Empress II (11.12 +/- 1.78 MPa).
      There were no significant differences among the ARI scores. The mode of failure
      was a mixture of adhesive and cohesive failure. CONCLUSION: The results indicate
      that the bond strengths of stainless steel orthodontic brackets bonded to Finesse
      and Empress II porcelains are clinically acceptable.

PMID- 16433079
TI  - Levels of t-PA and PAI-2 in gingival crevicular fluid during orthodontic tooth
      movement in adults.
AB  - BACKGROUND: The regulation of plasminogen activation is a key element in
      controlling proteolytic events in the extracellular matrix. OBJECTIVE: The aim of
      this study was to investigate gingival crevicular fluid (GCF) levels of tissue
      plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI -2) during
      orthodontic tooth movement in adults. METHODS: Five male subjects (Mean age: 22.5
      +/- 2.8 years) and five female subjects (Mean age: 23.4 +/- 3.9 years) were used.
      Each subject had one upper canine retracted into an extraction space. The
      contralateral and opposing canines, which were not moved, served as controls. GCF
      was collected at the distal cervical margins of the experimental and control
      teeth 0, 1, 24, and 168 hours after a retracting force was placed. GCF levels of
      t-PA and PAI-2 were determined by commercially available ELISA kits. RESULTS:
      After 24 hours of tooth movement the levels of t-PA and PAI-2 in the GCF were
      significantly higher from the experimental canines compared with the control
      teeth. There were no significant experimental-control differences at 0, 1, and
      168 hours. There were no differences in the total protein levels up to 168 hours
      after orthodontic tooth movement. CONCLUSIONS: These results indicate that the
      amounts of t-PA and PAI-2 in the GCF increase with orthodontic tooth movement,
      and suggest that such increases may be involved in extracellular matrix
      degradation in response to mechanical stress. Failure to detect elevated levels
      of t-PA and PAI-2 at 168 hours was attributed to decay of the force retracting
      the canines.

PMID- 16433080
TI  - Fixed presurgical orthopaedics for bilateral cleft lip and palate.
AB  - BACKGROUND: Presurgical orthopaedics has been employed since the 1950s as an
      adjunctive neonatal therapy for the correction of cleft lip and palate. It is
      accepted that presurgical orthopaedic plates facilitate lip repair and balanced
      orofacial growth. AIMS: The aims of this retrospective study of newborns with
      bilateral cleft lip and palate were two-fold: to describe the use of a fixed
      appliance to reposition the displaced fragments, and to determine if the
      magnitude of the palatal changes was age-related. METHODS: Study models of 12
      infants with bilateral cleft lip and palate were used. The models recorded the
      condition prior to expansion (2-3 weeks after birth) and at the end of retention
      (at the time of lip surgery). The intercanine width, intertuberosity width,
      palatal length, palatal depth and intercanine arch length were measured. RESULTS:
      As a result of the expansion the intercanine width and intertuberosity width
      increased, and the palatal length and intercanine arch length decreased. These
      changes were not age-related. CONCLUSIONS: Fixed presurgical orthopaedic
      expansion appliances can be used to expand the upper facial skeleton in newborns.

PMID- 16433081
TI  - Patients' attitudes towards compliance with retainer wear.
AB  - OBJECTIVES: The objectives of this survey were to determine patients' attitudes
      towards retainers and their compliance in wearing retainers. METHODS: Three
      hundred dental school patients were selected at random and survey questionnaires
      were distributed. Twelve private orthodontists were willing to participate in the
      survey and each was given 20 questionnaires for distribution to their patients.
      The questionnaire was designed to gather information regarding compliance in
      wearing removable retainers, perception of the comfort level of retainers and
      acceptance of the appearance of removable and fixed retainers. RESULTS: The
      results revealed that compliance in wearing an upper retainer was related to its
      comfort level and acceptance. Discomfort was the main reason given by dental
      school patients and forgetfulness was the major reason given by private patients
      for not wearing retainers. Higher proportions of patients found fixed retainers
      more comfortable to wear and were more willing to accept the appearance of fixed
      retainers. A higher proportion of private patients accepted the appearance of
      retainers compared with dental school patients, while a higher proportion of
      dental school patients found retainers less comfortable to wear than private
      patients. CONCLUSIONS: There was a strong relationship between compliance and
      comfort level in wearing upper removable retainers. Patients found fixed
      retainers more acceptable than removable types because of appearance and comfort.

PMID- 16433082
TI  - Visual application of the American Board of Orthodontics Grading System.
AB  - BACKGROUND: Assessment of treatment outcomes has traditionally been accomplished
      using the subjective opinion of experienced clinicians. Reduced subjectivity in
      the assessment of orthodontic treatment can be achieved with the use of an
      occlusal index. To implement an index for quality assurance purposes is time
      consuming and subject to the inherent error of the index. Quality assessment of
      orthodontic treatment on a routine basis has been difficult to implement in
      private practice. OBJECTIVES: To investigate whether a clinician can accurately
      apply the American Board of Orthodontics Objective Grading System by direct
      visual inspection instead of measuring individual traits. METHODS: A random
      sample of 30 cases was selected, including pretreatment and post-treatment upper
      and lower study casts and panoramic radiographs. The cases were examined and
      scored with the standardized measuring gauge according to the protocol provided
      by the American Board of Orthodontics (ABO). The records were re-examined 6 weeks
      later and the individual traits scored by visual inspection (VI). RESULTS: There
      were no significant differences between the pre- and post-treatment ABO gauge and
      VI scores. CONCLUSIONS: This study suggests that occlusal traits defined by the
      ABO Objective Grading System can be accurately assessed by visual inspection. The
      VI score provides a simple and convenient method for critical evaluation of
      treatment outcome by a clinician.

PMID- 16433083
TI  - Continuing professional education, reflective learning: the evidence is your own
      experience.

PMID- 16433084
TI  - Product traceability.

PMID- 16433085
TI  - Effects of adenoidectomy and changed mode of breathing.

PMID- 16433086
TI  - The social six: is that all there is?

PMID- 16433087
TI  - Introduction: food crops in a changing climate.
AB  - Changes in both the mean and the variability of climate, whether naturally
      forced, or due to human activities, pose a threat to crop production globally.
      This paper summarizes discussions of this issue at a meeting of the Royal Society
      in April 2005. Recent advances in understanding the sensitivity of crops to
      weather, climate and the levels of particular gases in the atmosphere indicate
      that the impact of these factors on crop yields and quality may be more severe
      than previously thought. There is increasing information on the importance to
      crop yields of extremes of temperature and rainfall at key stages of crop
      development. Agriculture will itself impact on the climate system and a greater
      understanding of these feedbacks is needed. Complex models are required to
      perform simulations of climate variability and change, together with predictions
      of how crops will respond to different climate variables. Variability of climate,
      such as that associated with El Nino events, has large impacts on crop
      production. If skilful predictions of the probability of such events occurring
      can be made a season or more in advance, then agricultural and other societal
      responses can be made. The development of strategies to adapt to variations in
      the current climate may also build resilience to changes in future climate.
      Africa will be the part of the world that is most vulnerable to climate
      variability and change, but knowledge of how to use climate information and the
      regional impacts of climate variability and change in Africa is rudimentary. In
      order to develop appropriate adaptation strategies globally, predictions about
      changes in the quantity and quality of food crops need to be considered in the
      context of the entire food chain from production to distribution, access and
      utilization. Recommendations for future research priorities are given.

PMID- 16433088
TI  - Probabilistic prediction of climate using multi-model ensembles: from basics to
      applications.
AB  - The development of multi-model ensembles for reliable predictions of inter-annual
      climate fluctuations and climate change, and their application to health,
      agronomy and water management, are discussed.

PMID- 16433089
TI  - Aspects of climate change prediction relevant to crop productivity.
AB  - Projected changes in surface climate are reviewed at a range of temporal scales,
      with an emphasis on tropical northern Africa--a region considered to be
      particularly vulnerable to climate change. Noting the key aspects of 'weather'
      affecting crop yield, we then consider relevant and projected change using output
      from a range of state of the art global climate models (GCMs), and for different
      future emission scenarios. The outputs from the models reveal significant inter
      model variation in the change expected by the end of the twenty-first century for
      even the lowest IPCC emission scenario. We provide a set of recommendations on
      future model diagnostics, configurations and ease of use to close further the gap
      between GCMs and smaller-scale crop models. This has the potential to empower
      countries to make their own assessments of vulnerability to climate change
      induced periods of food scarcity.

PMID- 16433090
TI  - Global food insecurity. treatment of major food crops with elevated carbon
      dioxide or ozone under large-scale fully open-air conditions suggests recent
      models may have overestimated future yields.
AB  - Predictions of yield for the globe's major grain and legume arable crops suggest
      that, with a moderate temperature increase, production may increase in the
      temperate zone, but decline in the tropics. In total, global food supply may show
      little change. This security comes from inclusion of the direct effect of rising
      carbon dioxide (CO2) concentration, [CO2], which significantly stimulates yield
      by decreasing photorespiration in C3 crops and transpiration in all crops.
      Evidence for a large response to [CO2] is largely based on studies made within
      chambers at small scales, which would be considered unacceptable for standard
      agronomic trials of new cultivars or agrochemicals. Yet, predictions of the
      globe's future food security are based on such inadequate information. Free-Air
      Concentration Enrichment (FACE) technology now allows investigation of the
      effects of rising [CO2] and ozone on field crops under fully open-air conditions
      at an agronomic scale. Experiments with rice, wheat, maize and soybean show
      smaller increases in yield than anticipated from studies in chambers. Experiments
      with increased ozone show large yield losses (20%), which are not accounted for
      in projections of global food security. These findings suggest that current
      projections of global food security are overoptimistic. The fertilization effect
      of CO2 is less than that used in many models, while rising ozone will cause large
      yield losses in the Northern Hemisphere. Unfortunately, FACE studies have been
      limited in geographical extent and interactive effects of CO2, ozone and
      temperature have yet to be studied. Without more extensive study of the effects
      of these changes at an agronomic scale in the open air, our ever-more
      sophisticated models will continue to have feet of clay.

PMID- 16433091
TI  - Crop responses to climatic variation.
AB  - The yield and quality of food crops is central to the well being of humans and is
      directly affected by climate and weather. Initial studies of climate change on
      crops focussed on effects of increased carbon dioxide (CO2) level and/or global
      mean temperature and/or rainfall and nutrition on crop production. However, crops
      can respond nonlinearly to changes in their growing conditions, exhibit threshold
      responses and are subject to combinations of stress factors that affect their
      growth, development and yield. Thus, climate variability and changes in the
      frequency of extreme events are important for yield, its stability and quality.
      In this context, threshold temperatures for crop processes are found not to
      differ greatly for different crops and are important to define for the major food
      crops, to assist climate modellers predict the occurrence of crop critical
      temperatures and their temporal resolution. This paper demonstrates the impacts
      of climate variability for crop production in a number of crops. Increasing
      temperature and precipitation variability increases the risks to yield, as shown
      via computer simulation and experimental studies. The issue of food quality has
      not been given sufficient importance when assessing the impact of climate change
      for food and this is addressed. Using simulation models of wheat, the
      concentration of grain protein is shown to respond to changes in the mean and
      variability of temperature and precipitation events. The paper concludes with
      discussion of adaptation possibilities for crops in response to drought and
      argues that characters that enable better exploration of the soil and slower leaf
      canopy expansion could lead to crop higher transpiration efficiency.

PMID- 16433092
TI  - Integrating seasonal climate prediction and agricultural models for insights into
      agricultural practice.
AB  - Interest in integrating crop simulation models with dynamic seasonal climate
      forecast models is expanding in response to a perceived opportunity to add value
      to seasonal climate forecasts for agriculture. Integrated modelling may help to
      address some obstacles to effective agricultural use of climate information.
      First, modelling can address the mismatch between farmers' needs and available
      operational forecasts. Probabilistic crop yield forecasts are directly relevant
      to farmers' livelihood decisions and, at a different scale, to early warning and
      market applications. Second, credible ex ante evidence of livelihood benefits,
      using integrated climate-crop-economic modelling in a value-of-information
      framework, may assist in the challenge of obtaining institutional, financial and
      political support; and inform targeting for greatest benefit. Third, integrated
      modelling can reduce the risk and learning time associated with adaptation and
      adoption, and related uncertainty on the part of advisors and advocates. It can
      provide insights to advisors, and enhance site-specific interpretation of
      recommendations when driven by spatial data. Model-based 'discussion support
      systems' contribute to learning and farmer-researcher dialogue. Integrated
      climate-crop modelling may play a genuine, but limited role in efforts to support
      climate risk management in agriculture, but only if they are used appropriately,
      with understanding of their capabilities and limitations, and with cautious
      evaluation of model predictions and of the insights that arises from model-based
      decision analysis.

PMID- 16433093
TI  - Integrated approaches to climate-crop modelling: needs and challenges.
AB  - This paper discusses the need for a more integrated approach to modelling changes
      in climate and crops, and some of the challenges posed by this. While changes in
      atmospheric composition are expected to exert an increasing radiative forcing of
      climate change leading to further warming of global mean temperatures and shifts
      in precipitation patterns, these are not the only climatic processes which may
      influence crop production. Changes in the physical characteristics of the land
      cover may also affect climate; these may arise directly from land use activities
      and may also result from the large-scale responses of crops to seasonal,
      interannual and decadal changes in the atmospheric state. Climate models used to
      drive crop models may, therefore, need to consider changes in the land surface,
      either as imposed boundary conditions or as feedbacks from an interactive climate
      vegetation model. Crops may also respond directly to changes in atmospheric
      composition, such as the concentrations of carbon dioxide (CO2), ozone (03) and
      compounds of sulphur and nitrogen, so crop models should consider these processes
      as well as climate change. Changes in these, and the responses of the crops, may
      be intimately linked with meteorological processes so crop and climate models
      should consider synergies between climate and atmospheric chemistry. Some crop
      responses may occur at scales too small to significantly influence meteorology,
      so may not need to be included as feedbacks within climate models. However, the
      volume of data required to drive the appropriate crop models may be very large,
      especially if short-time-scale variability is important. Implementation of crop
      models within climate models would minimize the need to transfer large quantities
      of data between separate modelling systems. It should also be noted that crop
      responses to climate change may interact with other impacts of climate change,
      such as hydrological changes. For example, the availability of water for
      irrigation may be affected by changes in runoff as a direct consequence of
      climate change, and may also be affected by climate-related changes in demand for
      water for other uses. It is, therefore, necessary to consider the interactions
      between the responses of several impacts sectors to climate change. Overall,
      there is a strong case for a much closer coupling between models of climate,
      crops and hydrology, but this in itself poses challenges arising from issues of
      scale and errors in the models. A strategy is proposed whereby the pursuit of a
      fully coupled climate-chemistry-crop-hydrology model is paralleled by continued
      use of separate climate and land surface models but with a focus on consistency
      between the models.

PMID- 16433094
TI  - Socio-economic and climate change impacts on agriculture: an integrated
      assessment, 1990-2080.
AB  - A comprehensive assessment of the impacts of climate change on agro-ecosystems
      over this century is developed, up to 2080 and at a global level, albeit with
      significant regional detail. To this end an integrated ecological-economic
      modelling framework is employed, encompassing climate scenarios, agro-ecological
      zoning information, socio-economic drivers, as well as world food trade dynamics.
      Specifically, global simulations are performed using the FAO/IIASA agro
      ecological zone model, in conjunction with IIASAs global food system model, using
      climate variables from five different general circulation models, under four
      different socio-economic scenarios from the intergovernmental panel on climate
      change. First, impacts of different scenarios of climate change on bio-physical
      soil and crop growth determinants of yield are evaluated on a 5' X 5'
      latitude/longitude global grid; second, the extent of potential agricultural land
      and related potential crop production is computed. The detailed bio-physical
      results are then fed into an economic analysis, to assess how climate impacts may
      interact with alternative development pathways, and key trends expected over this
      century for food demand and production, and trade, as well as key composite
      indices such as risk of hunger and malnutrition, are computed. This modelling
      approach connects the relevant bio-physical and socio-economic variables within a
      unified and coherent framework to produce a global assessment of food production
      and security under climate change. The results from the study suggest that
      critical impact asymmetries due to both climate and socio-economic structures may
      deepen current production and consumption gaps between developed and developing
      world; it is suggested that adaptation of agricultural techniques will be central
      to limit potential damages under climate change.

PMID- 16433095
TI  - Quantification of physical and biological uncertainty in the simulation of the
      yield of a tropical crop using present-day and doubled CO2 climates.
AB  - The impacts of climate change on crop productivity are often assessed using
      simulations from a numerical climate model as an input to a crop simulation
      model. The precision of these predictions reflects the uncertainty in both
      models. We examined how uncertainty in a climate (HadAM3) and crop General Large
      Area Model (GLAM) for annual crops model affects the mean and standard deviation
      of crop yield simulations in present and doubled carbon dioxide (CO2) climates by
      perturbation of parameters in each model. The climate sensitivity parameter
      (gamma, the equilibrium response of global mean surface temperature to doubled
      CO2) was used to define the control climate. Observed 1966-1989 mean yields of
      groundnut (Arachis hypogaea L.) in India were simulated well by the crop model
      using the control climate and climates with values of gamma near the control
      value. The simulations were used to measure the contribution to uncertainty of
      key crop and climate model parameters. The standard deviation of yield was more
      affected by perturbation of climate parameters than crop model parameters in both
      the present-day and doubled CO2 climates. Climate uncertainty was higher in the
      doubled CO2 climate than in the present-day climate. Crop transpiration
      efficiency was key to crop model uncertainty in both present-day and doubled CO2
      climates. The response of crop development to mean temperature contributed little
      uncertainty in the present-day simulations but was among the largest contributors
      under doubled CO2. The ensemble methods used here to quantify physical and
      biological uncertainty offer a method to improve model estimates of the impacts
      of climate change.

PMID- 16433096
TI  - From GCM grid cell to agricultural plot: scale issues affecting modelling of
      climate impact.
AB  - General circulation models (GCM) are increasingly capable of making relevant
      predictions of seasonal and long-term climate variability, thus improving
      prospects of predicting impact on crop yields. This is particularly important for
      semi-arid West Africa where climate variability and drought threaten food
      security. Translating GCM outputs into attainable crop yields is difficult
      because GCM grid boxes are of larger scale than the processes governing yield,
      involving partitioning of rain among runoff, evaporation, transpiration, drainage
      and storage at plot scale. This study analyses the bias introduced to crop
      simulation when climatic data is aggregated spatially or in time, resulting in
      loss of relevant variation. A detailed case study was conducted using historical
      weather data for Senegal, applied to the crop model SARRA-H (version for millet).
      The study was then extended to a 10 degrees N-17 degrees N climatic gradient and
      a 31 year climate sequence to evaluate yield sensitivity to the variability of
      solar radiation and rainfall. Finally, a down-scaling model called LGO (Lebel
      Guillot-Onibon), generating local rain patterns from grid cell means, was used to
      restore the variability lost by aggregation. Results indicate that forcing the
      crop model with spatially aggregated rainfall causes yield overestimations of 10
      50% in dry latitudes, but nearly none in humid zones, due to a biased fraction of
      rainfall available for crop transpiration. Aggregation of solar radiation data
      caused significant bias in wetter zones where radiation was limiting yield. Where
      climatic gradients are steep, these two situations can occur within the same GCM
      grid cell. Disaggregation of grid cell means into a pattern of virtual synoptic
      stations having high-resolution rainfall distribution removed much of the bias
      caused by aggregation and gave realistic simulations of yield. It is concluded
      that coupling of GCM outputs with plot level crop models can cause large
      systematic errors due to scale incompatibility. These errors can be avoided by
      transforming GCM outputs, especially rainfall, to simulate the variability found
      at plot level.

PMID- 16433097
TI  - Operational seasonal forecasting of crop performance.
AB  - Integrated, interdisciplinary crop performance forecasting systems, linked with
      appropriate decision and discussion support tools, could substantially improve
      operational decision making in agricultural management. Recent developments in
      connecting numerical weather prediction models and general circulation models
      with quantitative crop growth models offer the potential for development of
      integrated systems that incorporate components of long-term climate change.
      However, operational seasonal forecasting systems have little or no value unless
      they are able to change key management decisions. Changed decision making through
      incorporation of seasonal forecasting ultimately has to demonstrate improved long
      term performance of the cropping enterprise. Simulation analyses conducted on
      specific production scenarios are especially useful in improving decisions,
      particularly if this is done in conjunction with development of decision-support
      systems and associated facilitated discussion groups. Improved management of the
      overall crop production system requires an interdisciplinary approach, where
      climate scientists, agricultural scientists and extension specialists are
      intimately linked with crop production managers in the development of targeted
      seasonal forecast systems. The same principle applies in developing improved
      operational management systems for commodity trading organizations, milling
      companies and agricultural marketing organizations. Application of seasonal
      forecast systems across the whole value chain in agricultural production offers
      considerable benefits in improving overall operational management of agricultural
      production.

PMID- 16433098
TI  - Climate change, global food supply and risk of hunger.
AB  - This paper reports the results of a series of research projects which have aimed
      to evaluate the implications of climate change for food production and risk of
      hunger. There are three sets of results: (a) for IS92a (previously described as a
      'business-as-usual' climate scenario); (b) for stabilization scenarios at 550 and
      750 ppm and (c) for Special Report on Emissions Scenarios (SRES). The main
      conclusions are: (i) the region of greatest risk is Africa; (ii) stabilization at
      750 ppm avoids some but not most of the risk, while stabilization at 550 ppm
      avoids most of the risk and (iii) the impact of climate change on risk of hunger
      is influenced greatly by pathways of development. For example, a SRES B2
      development pathway is characterized by much lower levels of risk than A2; and
      this is largely explained by differing levels of income and technology not by
      differing amounts of climate forcing.

PMID- 16433099
TI  - Climate change and food security.
AB  - Dynamic interactions between and within the biogeophysical and human environments
      lead to the production, processing, distribution, preparation and consumption of
      food, resulting in food systems that underpin food security. Food systems
      encompass food availability (production, distribution and exchange), food access
      (affordability, allocation and preference) and food utilization (nutritional and
      societal values and safety), so that food security is, therefore, diminished when
      food systems are stressed. Such stresses may be induced by a range of factors in
      addition to climate change and/or other agents of environmental change (e.g.
      conflict, HIV/AIDS) and may be particularly severe when these factors act in
      combination. Urbanization and globalization are causing rapid changes to food
      systems. Climate change may affect food systems in several ways ranging from
      direct effects on crop production (e.g. changes in rainfall leading to drought or
      flooding, or warmer or cooler temperatures leading to changes in the length of
      growing season), to changes in markets, food prices and supply chain
      infrastructure. The relative importance of climate change for food security
      differs between regions. For example, in southern Africa, climate is among the
      most frequently cited drivers of food insecurity because it acts both as an
      underlying, ongoing issue and as a short-lived shock. The low ability to cope
      with shocks and to mitigate long-term stresses means that coping strategies that
      might be available in other regions are unavailable or inappropriate. In other
      regions, though, such as parts of the Indo-Gangetic Plain of India, other
      drivers, such as labour issues and the availability and quality of ground water
      for irrigation, rank higher than the direct effects of climate change as factors
      influencing food security. Because of the multiple socio-economic and bio
      physical factors affecting food systems and hence food security, the capacity to
      adapt food systems to reduce their vulnerability to climate change is not
      uniform. Improved systems of food production, food distribution and economic
      access may all contribute to food systems adapted to cope with climate change,
      but in adopting such changes it will be important to ensure that they contribute
      to sustainability. Agriculture is a major contributor of the greenhouse gases
      methane (CH4) and nitrous oxide (N2O), so that regionally derived policies
      promoting adapted food systems need to mitigate further climate change.

PMID- 16433100
TI  - Climate change impacts on crop yield and quality with CO2 fertilization in China.
AB  - A regional climate change model (PRECIS) for China, developed by the UK's Hadley
      Centre, was used to simulate China's climate and to develop climate change
      scenarios for the country. Results from this project suggest that, depending on
      the level of future emissions, the average annual temperature increase in China
      by the end of the twenty-first century may be between 3 and 4 degrees C. Regional
      crop models were driven by PRECIS output to predict changes in yields of key
      Chinese food crops: rice, maize and wheat. Modelling suggests that climate change
      without carbon dioxide (CO2) fertilization could reduce the rice, maize and wheat
      yields by up to 37% in the next 20-80 years. Interactions of CO2 with limiting
      factors, especially water and nitrogen, are increasingly well understood and
      capable of strongly modulating observed growth responses in crops. More complete
      reporting of free-air carbon enrichment experiments than was possible in the
      Intergovernmental Panel on Climate Change's Third Assessment Report confirms that
      CO2 enrichment under field conditions consistently increases biomass and yields
      in the range of 5-15%, with CO2 concentration elevated to 550 ppm Levels of CO2
      that are elevated to more than 450 ppm will probably cause some deleterious
      effects in grain quality. It seems likely that the extent of the CO2
      fertilization effect will depend upon other factors such as optimum breeding,
      irrigation and nutrient applications.

PMID- 16433101
TI  - Climate science and famine early warning.
AB  - Food security assessment in sub-Saharan Africa requires simultaneous
      consideration of multiple socio-economic and environmental variables. Early
      identification of populations at risk enables timely and appropriate action.
      Since large and widely dispersed populations depend on rainfed agriculture and
      pastoralism, climate monitoring and forecasting are important inputs to food
      security analysis. Satellite rainfall estimates (RFE) fill in gaps in station
      observations, and serve as input to drought index maps and crop water balance
      models. Gridded rainfall time-series give historical context, and provide a basis
      for quantitative interpretation of seasonal precipitation forecasts. RFE are also
      used to characterize flood hazards, in both simple indices and stream flow
      models. In the future, many African countries are likely to see negative impacts
      on subsistence agriculture due to the effects of global warming. Increased
      climate variability is forecast, with more frequent extreme events. Ethiopia
      requires special attention. Already facing a food security emergency, troubling
      persistent dryness has been observed in some areas, associated with a positive
      trend in Indian Ocean sea surface temperatures. Increased African capacity for
      rainfall observation, forecasting, data management and modelling applications is
      urgently needed. Managing climate change and increased climate variability
      require these fundamental technical capacities if creative coping strategies are
      to be devised.

PMID- 16433103
TI  - Multi-agent modelling of climate outlooks and food security on a community garden
      scheme in Limpopo, South Africa.
AB  - Seasonal climate outlooks provide one tool to help decision-makers allocate
      resources in anticipation of poor, fair or good seasons. The aim of the 'Climate
      Outlooks and Agent-Based Simulation of Adaptation in South Africa' project has
      been to investigate whether individuals, who adapt gradually to annual climate
      variability, are better equipped to respond to longer-term climate variability
      and change in a sustainable manner. Seasonal climate outlooks provide information
      on expected annual rainfall and thus can be used to adjust seasonal agricultural
      strategies to respond to expected climate conditions. A case study of smallholder
      farmers in a village in Vhembe district, Limpopo Province, South Africa has been
      used to examine how such climate outlooks might influence agricultural strategies
      and how this climate information can be improved to be more useful to farmers.
      Empirical field data has been collected using surveys, participatory approaches
      and computer-based knowledge elicitation tools to investigate the drivers of
      decision-making with a focus on the role of climate, market and livelihood needs.
      This data is used in an agent-based social simulation which incorporates
      household agents with varying adaptation options which result in differing
      impacts on crop yields and thus food security, as a result of using or ignoring
      the seasonal outlook. Key variables are the skill of the forecast, the social
      communication of the forecast and the range of available household and community
      based risk coping strategies. This research provides a novel approach for
      exploring adaptation within the context of climate change.

PMID- 16433102
TI  - Weather patterns, food security and humanitarian response in sub-Saharan Africa.
AB  - Although considerable achievements in the global reduction of hunger and poverty
      have been made, progress in Africa so far has been very limited. At present, a
      third of the African population faces widespread hunger and chronic malnutrition
      and is exposed to a constant threat of acute food crisis and famine. The most
      affected are rural households whose livelihood is heavily dependent on
      traditional rainfed agriculture. Rainfall plays a major role in determining
      agricultural production and hence the economic and social well being of rural
      communities. The rainfall pattern in sub-Saharan Africa is influenced by large
      scale intra-seasonal and inter-annual climate variability including occasional El
      Nino events in the tropical Pacific resulting in frequent extreme weather event
      such as droughts and floods that reduce agricultural outputs resulting in severe
      food shortages. Households and communities facing acute food shortages are forced
      to adopt coping strategies to meet the immediate food requirements of their
      families. These extreme responses may have adverse long-term, impacts on
      households' ability to have sustainable access to food as well as the
      environment. The HIV/AIDS crisis has also had adverse impacts on food production
      activities on the continent. In the absence of safety nets and appropriate
      financial support mechanisms, humanitarian aid is required to enable households
      effectively cope with emergencies and manage their limited resources more
      efficiently. Timely and appropriate humanitarian aid will provide households with
      opportunities to engage in productive and sustainable livelihood strategies.
      Investments in poverty reduction efforts would have better impact if complemented
      with timely and predictable response mechanisms that would ensure the protection
      of livelihoods during crisis periods whether weather or conflict-related. With an
      improved understanding of climate variability including El Nino, the implications
      of weather patterns for the food security and vulnerability of rural communities
      have become more predictable and can be monitored effectively. The purpose of
      this paper is to investigate how current advances in the understanding of climate
      variability, weather patterns and food security could contribute to improved
      humanitarian decision-making. The paper will propose new approaches for
      triggering humanitarian responses to weather-induced food crises.

PMID- 16433104
TI  - Men's health: why is it important? Why should ANAC care?

PMID- 16433105
TI  - Nurse-delivered antiretroviral treatment adherence intervention for people with
      low literacy skills and living with HIV/AIDS.
AB  - People living with HIV/AIDS who have lower health literacy show poorer treatment
      adherence and more adverse health outcomes. The authors undertook the development
      and pilot testing of a brief HIV treatment adherence improvement counseling
      intervention for people with lower health literacy who were taking antiretroviral
      medications. Guided by a theory of health behavior change, health education
      principles for lower literacy populations, and formative research, the authors
      designed a two-session plus one booster session nurse-delivered HIV treatment
      adherence intervention. Results from a pilot test with 30 HIV-positive men and
      women with lower health literacy showed that the intervention increased HIV/AIDS
      knowledge, intentions to improve adherence, and self-efficacy for adhering to
      medications. Participants exposed to the intervention also showed improvement in
      medication adherence, with reductions in numbers of missed pills and reductions
      in numbers of doses taken off-schedule. These results suggest that relatively
      brief behavioral interventions that are tailored for people with lower health
      literacy may have a significant impact on health-related behaviors.

PMID- 16433106
TI  - HIV/AIDS patient satisfaction with hospitalization in the era of highly active
      antiretroviral therapy.
AB  - The purpose of this study was to investigate how HIV/AIDS patients evaluate
      hospitalizations and to contrast such evaluations with those of inpatients who
      were diagnosed with pneumonia or pleurisy. In all, 302 satisfaction survey
      records collected in 2002 from patients of U.S. hospitals were analyzed.
      Potential confounding variables were kept constant or statistically controlled.
      Patients with HIV/AIDS rated their care lower than patients with pneumonia or
      pleurisy. The survey section, Tests and Treatments, yielded a significant effect
      of diagnosis. In addition, there was a significant effect of diagnosis for two
      survey items: skill of the person who took your blood, and skill of the person
      who started the intravenous line. Results were discussed in terms of caregiver
      attitudes toward HIV/AIDS patients, and implications for nursing care were drawn.

PMID- 16433107
TI  - Enfuvirtide for nurses: answering patient questions on activity, safety, and
      lifestyle impact.
AB  - The introduction of enfuvirtide, the first self-administered parenteral
      antiretroviral, has reinforced the HIV nurse's role in patient education,
      support, and motivation. Detailed background knowledge of the drug will assist
      nurses to provide answers to common questions and concerns raised during patient
      training. Three particular concerns often raised are curiosity about how
      enfuvirtide works, what side effects can be expected, and how these and the
      process of daily injection will affect the patient's daily routine. This brief
      review is designed to provide nurse-educators with clinical information on these
      three issues to help them better provide the answers patients will need to help
      them feel confident self-administering this new drug.

PMID- 16433108
TI  - Neurologic and psychiatric complications of antiretroviral agents.
AB  - Advances in highly active antiretroviral therapy (HAART) aim to improve the
      efficacy of HIV drugs as well as the quality of life in HIV-infected patients.
      Neurologic and psychologic disturbances that occur because of HIV disease and
      therapy are of great concern, and because they can overlap and are often
      difficult to distinguish, their pathogenesis is not clearly understood.
      Furthermore, these complications can lead to decreased adherence, thereby
      interfering with treatment outcomes. Antiretrovirals, including nonnucleoside
      reverse transcriptase inhibitors, can penetrate the central nervous system (CNS)
      and suppress viral replication, but they can also exacerbate CNS side effects and
      neuropsychiatric symptoms. When deciding which HAART drug combination is most
      appropriate for a patient, clinicians must consider the individual's risk of CNS
      complications together with the efficacy of the specific HAART regimen.

PMID- 16433109
TI  - The nature of multidisciplinary HIV care in the ambulatory setting: a synthesis
      of the literature.
AB  - The purpose of this article is to provide a critical appraisal and synthesis of
      the literature relating to the provision of multidisciplinary HIV care in the
      ambulatory setting. As more people are living with HIV infection, and living
      longer, the demand for chronic care is great. Knowing what optimal care and
      treatment for people living with HIV/AIDS is and how to provide that care is an
      ongoing challenge. The literature suggests that the provision of care for HIV
      infected individuals varies across and within HIV/AIDS clinics. This variability
      in care practices may influence the health and well-being of patients, and
      negatively impact on access to such care by people with HIV/AIDS. The goal of
      reviewing the literature on HIV-ambulatory clinics was to provide a description
      of a typical clinic, its staffing components, the care practices carried out at
      such a clinic (and by whom), and some barriers to providing optimal care. The
      ultimate goal of this review is to establish what is currently known about the
      provision of these services so that this information may build on existing
      knowledge and thereby standards of care for HIV-ambulatory clinics can be
      developed that could be implemented on a wide-scale basis.

PMID- 16433110
TI  - Stress reduction as a means to enhance oral immunity in HIV-infected individuals.

PMID- 16433111
TI  - HIV/AIDS nursing research in the African context.

PMID- 16433112
TI  - Factors that influence the spread of HIV/AIDS among students of the University of
      Botswana.
AB  - The results discussed in this report are part of a larger study conducted among
      the students of the University of Botswana regarding their knowledge, attitudes,
      and behaviors related to HIV/AIDS. The study triangulated survey methods and
      focus group discussions. Five main areas were investigated: knowledge and
      personal experiences of HIV/AIDS, sexual behavior and practices, perceptions
      about risky sexual behavior on campus, and factors that influence the spread of
      HIV. This article reports high levels of risky behaviors such as alcohol and drug
      abuse; unprotected sex; frequent change of sexual partners; sex for financial
      gain, for prestige, for good grades, to relieve stress, and because of peer
      pressure; and casual sex as part of socializing.

PMID- 16433113
TI  - "Eating plastic," "winning the lotto," "joining the www"...descriptions of
      HIV/AIDS in Africa.
AB  - This report is based on qualitative data gathered through a series of focus group
      discussions with people living with HIV or AIDS and nurses in five African
      countries. Participants were asked which words or phrases people use to refer to
      the illness and to people living with the illness. A total of 261 respondents
      were involved in the 40 focus group discussions, and an analysis of the data
      identified 290 descriptions. The descriptions were classified into 7 categories,
      which were (from most to least common): attributional, neutral, death-related,
      physical feature-related, factual statements, lingering illness-related, and
      common illness-related. Whereas some terms were used in more than one country,
      others were unique to a specific country. The descriptions show many negative
      labels and beliefs, but also an awareness of the devastating effects of the
      illness on individuals.

PMID- 16433114
TI  - The symptom experience of people living with HIV/AIDS in Southern Africa.
AB  - This study describes the symptom experience of 743 men and women living with
      HIV/AIDS in Botswana, Lesotho, South Africa, and Swaziland. Data were obtained in
      2002 by using a cross-sectional design. A survey of participants included 17
      sociodemographic items and the 64-item Revised Sign and Symptom Checklist for
      Persons with HIV Disease. Results indicate a strong correlation between the
      frequency of reported symptoms and their intensity (r = .84, p < .00).
      Participants who reported having enough money for daily expenses also reported
      significantly fewer symptoms. There were no significant differences in symptom
      frequency between men and women or by location of residence. The study showed a
      complex picture of HIV-related symptoms in all four countries. Because of the
      high levels of symptoms reported, the results imply an urgent need for effective
      home- and community-based symptom management in countries where antiretroviral
      therapy is unavailable to help patients and their families manage and control
      AIDS symptoms and improve quality of life.

PMID- 16433115
TI  - Models of community/home-based care for people living with HIV/AIDS in Southern
      Africa.
AB  - The HIV/AIDS epidemic has placed a large burden on public health facilities in
      developing countries that are already functioning with limited resources. This
      has shifted the burden of care to families and communities, because public health
      services are often stretched beyond their capacities. A number of community/home
      based care models and services have evolved in response to this need. This report
      reviews the most common community- and home-based care models in use as well as
      the experiences of selected African countries in their use of community/home
      based care.

PMID- 16433116
TI  - Children's rights in the context of HIV/AIDS in Southern Africa.
AB  - Children in Southern Africa are living under extreme, difficult circumstances
      because of the spread of HIV/AIDS. Protecting and enhancing the rights of
      children can be regarded as an investment in the future. The principles
      identified in the World Fit for Children document from the United Nations
      International Children's Emergency Fund, within the context of HIV/AIDS, were
      used as a theoretical framework for a study conducted in one of the provinces of
      South Africa. A survey was conducted as a collaborative research project to map
      out critical trends regarding the fulfillment of children's rights, patterns, and
      structures of services available and the identification of capacity gaps. Right
      holders and duty bearers were interviewed, area surveys were conducted, and field
      observations were performed to determine data. Recommendations were made to raise
      the awareness of children's rights and to mobilize the community into action. To
      realize children's rights, emphasis must be placed on physical survival,
      development, and protection. Duty bearers should recognize and accept their
      responsibilities to establish, facilitate, manage, and/or control plans of action
      to address the devastating consequences of HIV/AIDS. Children should be empowered
      with knowledge, skills, and awareness to engage in and claim their rights.

PMID- 16433117
TI  - Surgical pathology of the parathyroid glands.

PMID- 16433118
TI  - Uncommon and relatively uncommon lesions of the female reproductive system.

PMID- 16433119
TI  - Who is who among urothelial neoplasms?

PMID- 16433120
TI  - Diverticular colitis.

PMID- 16433121
TI  - Molecular markers in breast cancer: current practice and future possibilities.

PMID- 16433122
TI  - Cytology and surgical pathology of the mediastinum.

PMID- 16433123
TI  - Cytology and surgical pathology of pleural cavities.

PMID- 16433124
TI  - Cytology and surgical pathology of neoplasms of the lung.

PMID- 16433125
TI  - Endoscopic ultrasound guided fine needle aspiration of the pancreas.

PMID- 16433126
TI  - Using imaging data in making orthopedic diagnoses.

PMID- 16433127
TI  - Selected case studies in hematopathology: application of current ancillary
      techniques in diagnosis.

PMID- 16433129
TI  - Demystifying the diagnosis of gliomas.

PMID- 16433128
TI  - Aggressive B-cell lymphomas.

PMID- 16433130
TI  - Odontogenic tumors for general pathologists.

PMID- 16433131
TI  - Effective communication of antimicrobial susceptibility data by pathologists to
      clinicians.
AB  - As antimicrobial-resistant gram-positive and gram-negative bacterial infections
      continue to emerge over time, influenced by selective pressure, and the costs of
      treating these infections increase, the ability of microbiology laboratories to
      accurately detect drug resistant bacteria and communicate susceptibility test
      results effectively to clinicians in a timely manner is more important than ever.
      Ongoing cooperation and coordination of activities among clinical pathologists,
      technical personnel, pharmacy, clinical services, and infection control using up
      to-date laboratory methodologies and interpretive criteria to develop laboratory
      reports that are transmitted efficiently through computerized communication
      systems for use within each particular institution are essential to provide
      optimum patient care, control resistance, and conserve resources.

PMID- 16433132
TI  - Acquisition and use of digital images for pathology education and practice.

PMID- 16433133
TI  - The revised National Tuberculosis Control Programme: the gains and the future
      road map.

PMID- 16433134
TI  - Validation and reproducibility of a food frequency questionnaire to assess energy
      and fat intake in affluent north Indians.
AB  - BACKGROUND: India is currently witnessing a sharp rise in noncommunicable
      disorders such as obesity, diabetes, hypertension and cardiovascular diseases.
      This rise can be related in part to dietary changes such as increased intake of
      calories, fat (especially saturated fat) and cholesterol. A simple, accurate and
      reproducible method to measure these nutrients is essential to study the role of
      diet in these diseases in epidemiological studies. We aimed to develop and
      validate a food frequency questionnaire that could be used for this purpose.
      METHODS: Thirty urban north Indian subjects (age 23-64 years, 16 men) belonging
      to a high socioeconomic group were studied. The subjects were selected
      consecutively over a period of 3 weeks from among those participating in an
      epidemiological survey on cardiovascular risk factors in an affluent population.
      A 102-item food frequency questionnaire was developed to capture the intake of
      calories, fat, saturated fat and cholesterol. The results obtained by the food
      frequency questionnaire were compared with a 5-day diet record. To assess the
      reproducibility of the food frequency questionnaire, it was re-administered after
      3 months to the 23 subjects available. RESULTS: It took the dietician 20 minutes
      or less to administer the questionnaire. There was good correlation between the
      nutrient values as calculated by the food frequency questionnaire and 5-day diet
      record. The correlation for energy intake was 0.80, and varied between 0.55 and
      0.69 for unadjusted intake of other nutrients. After adjusting for calories, the
      correlation varied between 0.45 and 0.68. In general, the food frequency
      questionnaire overestimated the energy-adjusted nutrient intake by 6%-17%. When
      intake was classified into quartiles, there was good agreement between the two
      methods: 43%-100% for calories; 29%-86% for other nutrients for unadjusted
      intake; 29%-71% for nutrients after energy adjustment. On calculation of intake
      after re-administration of the food frequency questionnaire, there was a moderate
      to strong correlation (energy adjusted r=0.49-0.90) between the two evaluations
      for various nutrients. CONCLUSION: The food frequency questionnaire developed for
      the assessment of nutrient intake in a north Indian population was easy to
      administer, showed moderate to good correlation with the 5-day diet record and
      was reproducible.

PMID- 16433135
TI  - Non-invasive diagnosis of coronary artery disease with 16-slice computed
      tomography.
AB  - BACKGROUND: The gold standard for the diagnosis of coronary artery disease (CAD)
      is catheter angiography. However, catheter angiography is invasive and may not
      always be followed by interventional therapy. We report our results with the use
      of multislice computed tomography (MSCT) as a non-invasive diagnostic tool for
      CAD. METHODS: Thirty-one patients (26 with chronic stable angina, 5 with coronary
      anomalies) underwent 16-slice MSCT and catheter angiography. Vessels < 1.5 mm in
      diameter were excluded. The ability of MSCT to detect obstructive CAD (stenosis >
      or =50% of the diameter) was evaluated in pre-defined vessel segments. The
      association of calcium score with obstructive CAD, and the effect of heart rate
      on distal vessel visibility were also studied. RESULTS: There were 29 men and 2
      women (age range: 36-80 years; mean [SD]: 53 [11] years). Of the 403 vessel
      segments, 391 were > 1.5 mm in diameter and 321 were interpretable on both
      modalities. The non-interpretability rates were 7% (26/391) for catheter
      angiography and 14% (54/ 391) for MSCT, with distal location (64%; 34), motion
      artifacts (29%; 16) and calcification (7%; 4) being chiefly responsible in case
      of the latter technique. The sensitivity, specificity, positive and negative
      predictive values of MSCT were 85% (95% confidence interval [CI]: 73-93), 94%
      (95% CI: 90-96), 76% (95% CI: 64-85) and 96% (95% CI: 93-98), respectively. MSCT
      correctly classified patients with no, single-, double- and triple-vessel disease
      in 87% of cases. One patient was incorrectly excluded on MSCT; catheter
      angiography showed 50%-70% stenosis in this case. Patients with obstructive CAD
      had a higher Agatston score equivalent (p=0.03). There was no significant effect
      of heart rate on distal segment visibility. MSCT correctly identified all
      coronary anomalies. CONCLUSION: MSCT has a good potential for the detection of
      coronary stenosis, and may be most useful for excluding CAD (due to its high
      negative predictive value). It accurately delineates coronary anomalies.

PMID- 16433136
TI  - Protection from ultraviolet radiation by spectacle lenses available in India: a
      comparative study.
AB  - BACKGROUND: Exposure to ultraviolet radiation (UVR) can result in several ocular
      ailments. We studied the UV absorption (UV-A and -B bands) in 20 lenses (11 hard
      resin and 9 glass) commonly available in India as uncut lenses for the purpose of
      prescription as well as non-prescription wear. METHODS: Using a UV-visible
      spectrophotometer (Thermo-Spectronic, UV-1 model, Thermo Electron Corporation,
      USA), the percentage transmittance was scanned between 190 and 400 nm, from which
      the results at 280, 320, 340, 360, 380 and 400 nm were analysed. RESULTS: At 360
      nm (UV-A), 75% of the lenses studied failed to offer 95% protection as
      recommended by the United States Food and Drug Administration (US FDA). At 280 nm
      (UV-B), 35% of the lenses failed to offer 99% protection against UV-B. Hard resin
      lenses showed a higher degree of variation in protection from UV-A. CONCLUSIONS:
      Most of the lenses studied failed to meet the US FDA recommendations in terms of
      protection from UV-A. Glass lenses afforded better protection up to 320 nm
      compared with hard resin lenses. As the claims of lens manufacturers regarding
      UVR protection fall short of international standards, certification of UVR
      protection for different lenses should be introduced in India.

PMID- 16433137
TI  - Screening of patients with acute febrile illness for leptospirosis using clinical
      criteria and serology.
AB  - BACKGROUND: Leptospirosis is one of the common zoonoses but, in most instances,
      the infection goes unnoticed. Rapid diagnostic modalities are needed to diagnose
      the disease in the early stages. We assessed the usefulness of clinical criteria
      and compared these with enzyme-linked immunosorbentassay (ELISA) for the early
      detection of leptospirosis. METHODS: One hundred patients with a febrile illness
      for > 7 days were screened by Faine criteria and their sera were subjected to
      both IgM and IgG ELISA using a commercially available kit (Institut Virion Serion
      GmbH, Warburg, Germany). RESULTS: Twenty-six patients satisfied the clinical
      criteria for leptospirosis and 8 of them tested positive for IgM antibodies while
      1 patient who was clinically negative tested positive by serology. Thus, Faine
      criteria had a sensitivity of 88.9%, specificity of 80.2%, positive predictive
      value of 30.8% and a negative predictive value of 98.6%. Paired serum samples
      were obtained from 70 patients but the IgG levels of only 2 showed a 4-fold rise.
      CONCLUSION: Faine criteria has moderate sensitivity and specificity but a high
      negative predictive value in comparison with IgM ELISA. The high negative
      predictive value may help to screen patients with acute febrile illness for
      leptospirosis during the early phase of the disease.

PMID- 16433138
TI  - Myomatous erythrocytosis syndrome.
AB  - Uterine myomas are common but erythrocytosis caused by these is rarely seen. We
      report a case that illustrates the conjunction of various aetiological factors
      required for this clinical entity to evolve. A voluminous, retroperitoneally
      located and focally degenerated myoma was associated with severe secondary
      erythrocytosis (haematocrit: 65.5%) which resolved after hysterectomy. It has
      been demonstrated previously that myomatous tissue is the source of excessive
      production of erythropoietin. Local tissue hypoxia, which is more prone to
      develop in a pedunculated myoma, stimulates the process. Other prerequisites are
      a very large size of the myoma and the absence of menometrorrhagia of a severity
      such as to cause a depletion in iron reserves.

PMID- 16433140
TI  - Screening for colon cancer: virtual or real colonoscopy?

PMID- 16433139
TI  - Cancer metastasis: advances in the detection and characterization of disseminated
      tumour cells facilitate clinical translation.

PMID- 16433141
TI  - Live-birth after transplantation of cryopreserved ovarian tissue.

PMID- 16433143
TI  - Salivating rooms.

PMID- 16433142
TI  - Methodological issues in setting up a surveillance system for birth defects in
      India.
AB  - India is undergoing an epidemiological transition--communicable diseases are on
      the decline due to better living conditions and healthcare delivery. On the other
      hand, the relative increase in the prevalence of non-communicable, chronic and
      genetic diseases threatens to be a public health problem in India. One such group
      of disorders is congenital malformations. Though several studies have been done
      on congenital malformations in India since the early 1960s, coinciding with the
      thalidomide tragedy in the West, no uniform methods are available for the
      surveillance of birth defects. Each study has come out with varying results, not
      only because of the geographic variation in birth defects but also due to the
      varying standards adopted by each study in data collection, case definition and
      other methodological issues. Setting up a mechanism to understand the extent and
      nature of birth defects would involve the creation of a birth defects registry.
      The goals and objectives of such a registry should be formulated before it is set
      up. There are three types of registries-descriptive, analytical and preventive.
      These can also be classified as population- or hospital-based. Whether a registry
      is population- or hospital-based depends largely on the movement of mothers for
      delivery, registration of vital events in an area defined by the programme, as
      well as the resources available to the registry. Data can be collected in a
      passive or active manner, which also depends on the resources available to the
      registry. Every registry should have its own working definition of eligible cases
      to be reported, depending on the diagnostic services available in that area, and
      multiple sources of information should be used to improve the ascertainment rate.
      All the diagnostic terms should be coded and the information collected should be
      stored in a well-constructed database, preferably a relational type. Registries
      must evaluate their methods of data collection periodically to estimate the
      number of false-positive and false-negative reports. Ethical issues, cost and
      funding for the employment of various specialized professionals should be
      considered before setting up a registry.

PMID- 16433144
TI  - Healthcare lobbying.

PMID- 16433145
TI  - The phoenix has risen.

PMID- 16433147
TI  - Psychological management of erectile dysfunction in primary care.

PMID- 16433146
TI  - Chronic diseases.

PMID- 16433148
TI  - Privately versus publicly managed primary healthcare.

PMID- 16433149
TI  - A triple burden.

PMID- 16433150
TI  - Snake-bite in India.

PMID- 16433151
TI  - Upper body venous thrombosis associated with ovarian stimulation: case report and
      review of the literature.
AB  - Thromboembolic events are a serious complication of assisted conception
      treatment. Thrombosis may be either arterial or venous but the latter is far more
      common. This phenomenon is more frequent in the lower limb, but several cases of
      upper extremity thrombosis have been described in the literature. Although the
      aetiology of these thromboembolic disorders is not fully understood, the
      mechanism is thought to be due to a hypercoagulable state associated with
      haemostasis and thrombophilia. Predisposing factors seem to be hyperoestrogenism,
      ovarian hyperstimulation syndrome, a hereditary hypercoagulable state and
      multifoetal pregnancy. We report a case of superior sagittal sinus thrombosis
      that developed in a patient following successful assisted conception in the
      absence of evident risk factors. In the current literature, the site of
      thrombosis, possible predisposing factors, oestrogen levels, number of foetuses,
      maternal and foetal outcomes, and management of thrombosis were analysed.

PMID- 16433152
TI  - Matched control study of efficacy of lymphocyte immunotherapy in donor oocyte
      recipients to support or refute the concept of need for histocompatibility
      antigen sharing of the couple for benefits.
AB  - PURPOSE: To determine if lymphocyte immunotherapy (LIT) improves outcome in
      recalcitrant donor oocyte recipients. If LIT was found to be similarly effective
      in this group, the theory of shared maternal/paternal histocompatibility antigens
      would seem less plausible because the donor oocyte introduces another group of
      histocompatibility antigens. METHODS: Donor oocyte recipients with a history of
      failure to conceive despite at least two previous ETs using donor oocytes were
      given the option of having LIT. They were matched with the very next recipient
      who declined LIT therapy. Lymphocyte immunotherapy using the male partner's
      lymphocytes was given two weeks before transfer and twice more if pregnant.
      RESULTS: Only three controls delivered versus recipients treated with LIT.
      CONCLUSIONS: The fact that benefit from LIT extended to oocyte recipients
      challenges the concept that lymphocyte immunotherapy is most beneficial for
      couples sharing histocompatibility antigens.

PMID- 16433153
TI  - Predictors of intracytoplasmic sperm injection (ICSI) outcome in couples with and
      without male factor infertility.
AB  - AIM: To find out the predictors of ICSI outcome. METHODS: Forty-three pregnancies
      in 100 consecutive ICSI cycles. RESULTS: Every 1,000 pg/ml increase in hCG-day E2
      (OR = 0.46, CI: 0.25-0.83, p = 0.01) and 1% decrease in the rate of normal sperm
      morphology (OR = 0.81, CI: 0.67-0.98, p = 0.03) caused a significant decrease in
      clinical pregnancy rate and live birth rate (respectively, OR = 0.5, CI: 0.32
      0.96, p = 0.03, OR = 0.66, CI: 0.5-0.86, p = 0.002) while every increase in the
      number of good quality embryos transferred caused a two-time increase in the
      clinical pregnancy rate (OR = 2.1, CI: 1.2-4, p = 0.01). On the other hand, every
      increase in the number of four-cell cleavage embryos (OR = 1.02, CI: 1.002-1.04,
      p = 0.03) and hCG-day endometrial thickness (OR = 1.6, CI: 1.15-2.24, p = 0.005)
      were found to increase the live birth rate. Implantation rate (m = 8.3 +/- 14.6)
      was significantly lower in cases with leucocytospermia (n = 33) compared to cases
      without leucocytospermia (n = 67, m = 17.4 +/- 24.6, p = 0.02). CONCLUSION:
      Leucocytospermia, hCG-day E2 level and endometrial thickness, normal sperm
      morphology, and number of good quality embryos are predictors of implantation,
      clinical pregnancy and live birth rate following ICSI.

PMID- 16433154
TI  - Safety of nelfinavir use during pregnancy. An experimental approach in rats.
AB  - This experimental study aimed to evaluate the safety of nelfinavir when
      administered in normal up to high doses during the entire period of rat
      pregnancy. The renal and liver compartments of both mothers and fetuses were
      studied. For this purpose, three groups of pregnant rats were treated with
      nelfinavir (E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg; no. = 10 in every
      group) from "zero" up to the 20th day of gestation. These doses were divided into
      two daily administrations by gavage. Controls (no. = 10) received distilled water
      in the same schedule. At term-pregnancy, the rats were deeply anesthesized and
      blood samples were collected for alanine and aspartate aminotransferases,
      creatinine and urea determinations. Fragments of maternal and fetal livers and
      kidneys were taken and processed for histopathological study. In all groups blood
      transaminases were within the normal limits, as were the levels of creatinine and
      urea, thus indicating that the treatment with nelfinavir during the entire
      gestation was essentially devoid of liver or kidney effects which could result in
      altered metabolic parameters. Morphological (light microscopy) studies revealed
      that no significant effects of the drug could be detected regarding either
      maternal or fetal organs of the E1 and E2 groups. However, the maternal
      hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was
      some fatty infiltration, congested sinusoids and portal dilatation. It is
      concluded that only doses of nelfinavir used during the entire gestation in doses
      well above the usual human doses could be considered to be potentially
      hepatotoxic for the pregnant rat.

PMID- 16433155
TI  - EGF and IGF-I as predictors of ICSI outcome in human preimplantation embryo
      cultures.
AB  - PURPOSE OF INVESTIGATION: Detection of EGF and IGF-I in human embryo cultures and
      their effect on ICSI outcome. METHODS: Collection of culture medium from embryos
      of 50 women under ICSI program. EGF and IGF-I were measured via enzyme
      immunoassay. RESULTS: ICSI outcome was independent of age, infertility years,
      FSH, LH, prolactine and E2. EGF detection was higher in 48- (32%), than in 72
      hour embryos (14%) (p < 0.001). EGF negative embryos are likely to be arrested at
      the morula stage (p < 0.001) and are associated with poor pregnancy rates (p <
      0.05). IGF-I was undetected in 48-hour embryos. CONCLUSIONS: For the first time
      human embryos were surveyed from fertilization until embryo transfer, regarding
      EGF and IGF-I production. IGF-I is not a predictor of ICSI outcome. EGF is
      present in one-third of human embryo cultures at 48 hours, but this ratio wanes
      at the morula stage. EGF negative embryos are associated with lower pregnancy
      rates.

PMID- 16433156
TI  - Microsurgery versus laparoscopy in distal tubal obstruction
      hysterosalpingographically or laparoscopically investigated.
AB  - OBJECTIVE: To compare pregnancy rates after laparotomic microsurgical or
      laparoscopic distal tuboplasty. DESIGN: Two hundred and twenty-four women with
      infertility due to distal tubal occlusion were randomized to be treated with
      either laparotomy or laparoscopy from 1987 to 2001 at the Institute of
      Gynaecology and Obstetrics, University of Rome, "La Sapienza". RESULTS: The
      results were evaluated taking into account the type of surgical approach, the
      severity of tubal damage and of adhesions. After a 24-month follow-up period, the
      overall pregnancy rate obtained with microsurgery was 43.7%, of which 33.3% were
      term pregnancies, 5.0% abortions, and 5.0% ectopic pregnancies. After
      laparoscopy, the overall pregnancy rate was 41.6%, of which 29.1% were term
      pregnancies, 8.3% abortions and 3.9% ectopic pregnancies. No significant
      differences was observed between the two groups in terms of fertility rate (chi
      square 0.016, p = 0.9003). CONCLUSIONS: Laparotomy plus microsurgery and
      laparoscopy were equally effective in restoring fertility in women with
      comparable tubal damage. The severity of the damage is a critical factor for the
      results.

PMID- 16433157
TI  - Comparison of clinical diagnosis and microbiological test results in vaginal
      infections.
AB  - Lower genital tract infections continue to be a problem due to the fact that the
      clinical diagnosis is usually inadequate, and subsequent care is suboptimal. This
      study aimed at evaluating the accuracy of clinical diagnosis by comparing it with
      microbiologic test results, and to determine the causative agents of vaginal
      infections. Sixty-seven nonpregnant women (18-45 years of age) with the clinical
      diagnosis of lower genital tract infection were enrolled in the study. Patients
      were not included if they had a history of vaginal infection during the previous
      three-month period or intrauterine device. The clinical diagnosis was based on
      the combinations of symptoms, direct observation of wet mount, homogeneous
      discharge, vaginal pH > 4.5, and detection of the amine odor after exposure of
      vaginal secretions to 10% KOH. Vaginal samples were taken with two cotton swabs,
      one was used for pH determination, and the second was utilized for
      microbiological tests. Gram staining and cultures with Sabouraud agar and
      chocolate agar were performed for microbiological diagnosis, and the results were
      compared. The clinical diagnoses included 26 (38.8%) candidiasis, 18 (26.8%)
      bacterial vaginosis, three (4.5%) trichomoniasis, and 20 (29.9%) mixed vaginal
      infections. Of the 26 patients with clinical diagnoses of candidiasis, 12 (46.1%)
      revealed Candiada albicans, nine (34.6) patients revealed microorganisms other
      than candida species, and five (19.2%) patients had no growth. Five (27.8%)
      bacterial vaginosis patients revealed Gardnarella vaginalis and 12 patients
      (66.6%) did not grow any microorganism. The overall rate of accurate clinical
      diagnoses confirmed by microbiological test results was 43.2%. Seventeen (43.6)
      of the 39 microbiological test results correlated with clinical diagnosis, and no
      growth was observed in 28 (41.8%) cultures. We conclude that the clinical
      diagnosis of vaginal infection is inadequate and should be confirmed with
      microbiological testing if the resources are avaliable.

PMID- 16433158
TI  - Serum cystatin C in pregnant women: reference values, reliable and superior
      diagnostic accuracy.
AB  - BACKGROUND: A simple, endogenous, accurate and minimally invasive marker of
      glomerular filtration rate (GFR) is much desired in clinical nephrology. Cystatin
      C fulfills all criteria to be a marker for GFR. For early detection of renal
      impairment in pregnant women, it is necessary to determine serum cystatin C
      reference values and the correlation with GFR. The present study was therefore
      undertaken. METHOD: Healthy pregnant women were followed during pregnancy and the
      postnatal period. Patient demographics included age, height, weight, BMI, parity,
      total blood count, LFT, urea, creatinine, Na, K, and blood sugar. Serum cystatin
      C was estimated using particle enhanced nephlo-immunoassay method. All the
      parameters were recorded at the start of pregnancy and then in each trimester and
      the postnatal period. Regression analysis correlation coefficient, ANOVA and the
      Student's t-test were used for analysis using the SPSS statistical package.
      RESULTS: A total of 197 pregnant women were included. Mean serum cystatin C for
      all the women was 0.82 +/- 0.184 mg/l. Serum cystatin C levels were high -0.89 +/
      0.12 mg/l in the first trimester, decreased significantly to 0.651 +/- 0.14 mg/l
      during the second trimester (p = 0.0000 compared to first trimester), and
      increased again to 0.82 +/- 0.191 mg/l in the third trimester. After delivery the
      level rose to 0.94 +/- 0.12 mg/l. A strong correlation was found between serum
      cystatin C and serum creatinine. A strong negative correlation was found between
      GFR and cystatin C values in the women (r = -0.546, p = 0.000). A linear
      relationship was found between GFR and cystatin C levels. A significant increase
      in the GFR was noted with the progression of pregnancy from 128.06 +/- 29.7
      ml/min in the first trimester to 155.2 +/- 29.59 ml/min during second trimester
      (p = 0.006). A decline in the level of cystatin C exactly parallel to the
      increase in the GFR was noted with the progression of pregnancy. Interestingly
      cystatin C was found to have a strong negative correlation with gestational age
      (r = -0.663, p = 0.000). CONCLUSION: Our results indicate that the mean serum
      cystatin C levels reflect changes in the GFR during the entire pregnancy and also
      in the postnatal period. Moreover, serum cystatin C levels are independent of
      age, height, weight, or blood sugar level. Cystatin C can be used for close
      supervision and early diagnosis of renal impairment in pregnant patients.
      Cystatin C is a reliable, useful and promising marker of GFR in pregnant women.

PMID- 16433159
TI  - Sex-induced cystitis--patient burden and other epidemiological features.
AB  - Although sexual intercourse has been established as an important risk factor for
      uncomplicated urinary tract infection (UTI) in women, the exact the rate of
      recurrent UTI due to sexual intercourse and its patient burden is unknown.
      According to our findings, sex-induced cystitis (SIC) accounts for almost 4% of
      lower urinary tract infections and for 60% of the recurrent cases. Is most
      frequent between 23 to 27 years and affect mainly women from low and median
      socioeconomic groups. Behavioral risk factors of SIC include frequency of sexual
      intercourse and the use of condoms, while the absence of a stable sexual
      companion does not add further risk. No seasonal variation has been observed in
      reinfections suspected of SIC. According to information obtained from our
      questionnaire each episode of this type of UTI in young women was shown to be
      associated with three to six days of symptoms and one to three days of restricted
      activity. E. coli was by far the most common pathogen accounting for 95% of
      primary UTI and 84% of recurrent SIC.

PMID- 16433160
TI  - The significance of detailed examination of hemorrhoids during pregnancy.
AB  - In the population of pregnant women in Serbia and Montenegro, hemorrhoids are
      present in 85% of the cases during the second and third pregnancy. Urged by the
      complications of non-treated hemorrhoids, we carried out a routine diagnostic
      procedure to examine hemorrhoids during pregnancy, i.e. a differential diagnosis
      with other possible complications was performed. Fifty patients, aged between 36
      and 38, were examined by anoscope and rectoscope during the second trimester.
      Rectal carcinoma was found in three cases, which is a disturbing number. The
      patient with the most serious clinical picture was subjected to urgent artificial
      fetal lung maturation and surgical delivery. One of the patients had clinical
      cachexia, and in view of the fact that the magnetic resonance imaging during
      pregnancy showed infiltration and that the patient was 38 years old, with the
      patient's consent, surgery was performed together with hysterectomy and salpingo
      oophorectomy and immediate removal of the rectum and anus. In the other two
      cases, the delivery ended vaginally between the 35th and 38th week of gestation,
      after which the patients were moved to the surgery ward. Besides a positive
      family history for digestive tract carcinoma (95%), smoking and increased body
      mass index, there were no significant parameters distinguishing these three
      patients from others with hemorrhoids. Interesting data were obtained from the
      fact that there was no increase in body mass during pregnancy which patients
      correlated with their already present obesity. Moreover, pain was correlated with
      the fact that the patients did not follow a healthy dietary regime. In all 50
      patients, the following procedures were performed: anoscope, rectoscope and
      digestive tract tumor markers. Observing the results of the biopsies, we found
      rectal carcinoma Stage C according to Dukes staging (tumor included serosa) in
      one case. In the other two cases, Stage B1 carcinomas were found (which included
      all layers except serosa). Magnetic resonance imaging was performed and confirmed
      progression of the disease. The delivery ended per vias naturalis in two cases in
      view of the fact that it was the third pregnancy for both patients. Surgery was
      performed 40 days after delivery. Postoperative recovery was unremarkable in all
      described cases.

PMID- 16433162
TI  - Factors influencing the initiation and progress of breastfeeding in Greece.
AB  - OBJECTIVE: The aim of this study was to investigate and assess the factors
      associated with the initiation, progress, and duration of breastfeeding in
      Greece. METHODS: We studied 1,010 infants born from 862 women from 1996 to 2000
      in 17 hospitals. We followed the mothers for the period January-October 2001,
      while they were at the maternity hospitals to give birth to their next child.
      RESULTS: Statistical analysis of the data showed that factors positively
      associated with the duration of breast-feeding were the application of rooming-in
      (p = 0.0001), the initiation time of breast-feeding--mainly one to six hours
      after delivery (p = 0.0004), natural delivery (p = 0), pleasant delivery (p =
      0.0142), the time the decision about breastfeeding was taken (p = 0), the fact
      that it was mainly a maternal decision and the mothers were not influenced by a
      specific person (p = 0.0272) and the fact that no mixed diet was administered (p
      = 0). Smoking was negatively associated with the duration of breastfeeding (p =
      0.0036). Factors not associated with the duration of breastfeeding were: number
      of the mother's family members (p = 0.1231), whether the women themselves were
      breastfed as babies (p = 0.03924), some elements of their personality (p =
      0.3871) as well as their beliefs concerning maternal milk (p = 0.1922).
      CONCLUSIONS: From our results we have indications as to which factors are related
      or unrelated to the initiation and progress of breastfeeding in Greece.

PMID- 16433161
TI  - Influence of a decisional tree on the route of hysterectomy for benign disease in
      Italy: personal experience.
AB  - BACKGROUND: Mainly to report our experience in the route of hysterectomy after
      introducing specific guidelines according to the Society of Pelvic Reconstructive
      Surgeons and to record all hysterectomy-related complications after abdominal and
      vaginal hysterectomies. METHODS: The records of 22 patients who underwent
      abdominal hysterectomy and 59 who underwent vaginal hysterectomy for benign
      disease were reviewed. Complications related to hysterectomy were recorded during
      surgery, postoperative hospital stay and a period of six weeks. Statistical
      methods used were t-tests and chi square analysis. RESULTS: Operation time was
      shorter with the vaginal route. Patients operated on via the vaginal route had
      less blood loss and shorter hospital stay. CONCLUSIONS: The main standard to
      select the route for hysterectomy is the severity of the clinical status.
      Decreasing the ratio between the abdominal and vaginal route is possible, but it
      is crucial to make the indications clear, based on scientific evidence.

PMID- 16433163
TI  - Efficacy of prophylaxis in women with sex induced cystitis.
AB  - Sexual intercourse has been established as one of the most important risk factors
      for both isolated and recurrent uncomplicated infections of the urinary tract.
      Prophylactic therapy requires only a small dose of an antimicrobial agent, which
      is generally given at bedtime for 6 to 12 months. An alternative method is to
      give an antimicrobial agent for six months post-intercourse. It is still unknown
      which of the two methods is most effective. A total of 123 women with suspected
      sexually induced recurrent cystitis (mean age 28 years, range 15 to 65) and a
      history of recurrent urinary tract infection (UTI) (the last one within the last
      six months) were subjected to prophylactic therapy for six months. Half of them
      were treated with low-dose trimethoprim-cotrimoxazole (TMP-SMX) and cefaclor
      given orally post-intercourse (spontaneous usage), while the other half were
      treated with low-dose TMP-SMX and cefaclor given at bedtime. The response to the
      prophylactic therapy was classified as continued cure in 106 cases (86.17%),
      failure in 13 cases (10.56%), and unknown in four cases (3.25%). TMP-SMX
      administered in continuous nightly prophylaxis showed similar efficacy and
      tolerability as cefaclor post-intercourse. OBJECTIVE: To determine the efficacy
      of prophylaxis in women with recurrent sex induced cystitis and compare the post
      intercourse versus the conventional bedtime given long-term, low-dose use of
      prophylactic antimicrobials.

PMID- 16433164
TI  - Asymptomatic struma ovarii: a case report.
AB  - Struma ovarii is a rare ovarian neoplasm. This tumor is generally benign,
      although malignant transformation has been reported. The preoperative diagnosis
      is generally difficult. Thyroid hormones may be produced and in a few cases
      asymptomatic women may develop definitive clinical hypothyroidism after resection
      of struma ovarii. We report a case of a 39-year-old woman who underwent
      laparoscopic resection of an asymptomatic right ovarian mass. The pathologic
      diagnosis was struma ovarii. The postoperative period was uneventful and her
      thyroid function remained normal.

PMID- 16433165
TI  - Pregnancy complicated with pulmonary lymphangioleiomyomatosis: case report.
AB  - A case of a 30-year-old primiparous woman with pulmonary lymphangioleiomyomatosis
      is described. The patient had experienced six episodes of spontaneous
      pneumothorax at the age of 27 years and had been diagnosed as having pulmonary
      lymphangioleiomyomatosis based on histological findings of specimens obtained by
      transbronchial biopsy. She had undertaken open lung surgery and thoracoscopy.
      Thereafter, she became pregnant spontaneously. Her antenatal course was
      uneventful with no exacerbation of respiratory status. At 38 weeks of gestation,
      she underwent a selective cesarean section and myomectomy under combined spinal
      and epidural anesthesia. Her postoperative course was uneventful. No remarkable
      changes in computed tomographic findings of the lung were noted on the 20th day
      of postoperation compared with those before pregnancy. She has been followed-up
      in the pulmonary outpatient clinic with no deterioration of the disease.

PMID- 16433166
TI  - Hyperemesis or stomach carcinoma in pregnancy--a true diagnosis with two lives
      saved: a case report.
AB  - The cause of stomach carcinoma is still unclear but a variety of possible factors
      are presently under investigation. The clinical signs of stomach carcinoma are
      deceitful, and the disease is mainly asymptomatic. The first symptoms are
      dyspeptic disturbances, the feeling of satiety after meals, belching, and loss of
      appetite. This interesting and educative case starts with an almost classical
      story of a patient admitted with hyperemesis during pregnancy. She was a
      primipara, 18 years old, with a significantly low body mass index and electrolyte
      imbalance and at the 23rd week of gestation.

PMID- 16433167
TI  - Ruptured heterotopic pregnancy with successful obstetrical outcome: a case report
      and review of the literature.
AB  - Emergency medicine has encountered in the last decades a gradual increase in
      cases of heterotopic pregnancy (HP) with rupture of the ectopic part. The rise of
      this entity is mainly due to ovulation induction performed in women undergoing
      assisted reproductive techniques (ART), but in natural cycles is still rare and
      unexpected. Diagnosis is often delayed especially in cases where no predisposing
      factors exist, causing life threatening situations. We report a case of a
      ruptured heterotopic pregnancy presenting at seven weeks of gestation that was
      treated with immediate laparotomy. The rest of the pregnancy course was
      uneventful with spontaneous vaginal delivery of a healthy infant at 39 weeks of
      gestation. A review of the diagnosis and management of heterotopic pregnancy is
      also given.

PMID- 16433168
TI  - Abdominal rectus muscle sheath abscess after spontaneous vaginal delivery. A case
      report.
AB  - Postpartum infections cause severe morbidity of the mother. Abdominal wound
      infection and abscess formation are common complications after cesarean delivery.
      We report a case with abscess formation inside the abdominal rectus muscle sheath
      after normal, spontaneous vaginal delivery. A 32-year-old woman, para 2, had a
      normal vaginal delivery at term. The second postpartum day she complained of
      lower abdominal pain and was unable to stand up or walk. The fourth day,
      cellulitis of the skin of the lower abdomen developed and was treated with broad
      spectrum intravenous antibiotics. The seventh day the patient developed septic
      fever and an abdominal rectus muscle sheath abscess was diagnosed. The abscess
      was treated with incisions and evacuation and the patient was discharged the 12th
      postoperative day. The abscess in this case, as hematoma formation was not
      preceded, was referred to ascending contamination via the lymphatic vessels.

PMID- 16433169
TI  - [Sarcoidosis as seronegative spondyloarthropathy].
AB  - Two cases were presented with initial symptoms of inflammatory low back pain and
      alternate buttock pain. They developed a progressive dyspnea with bilateral
      mediastinal and hiliar lymphadenopathy and pulmonary interstitial disease as
      visualized with chest CT scan. Sarcoidosis diagnosis was confirmed by biopsy in
      both cases--in one case by skin biopsy and in the other by open lung biopsy.
      These clinical forms of spondyloarthropathy and sarcoidosis were unusual and were
      compared with similar cases present in the literature.

PMID- 16433170
TI  - [Make the diagnosis].

PMID- 16433171
TI  - [Feeding behavior and glycemic profile in two lines of rats with genetic
      diabetes].
AB  - INTRODUCTION: Food intake can aggravate diabetes in humans and in animal models.
      In rat model systems, the eSMT rat strain shows increased diabetes expression and
      higher biomass than its eSS parental line. OBVJECTIVE: The feeding behavior of
      eSMT and eSS males was compared under conditions of ad libitum versus restrictive
      food intake. The effects on rat weight and glycemia were examined. MATERIALS AND
      METHODS: Unrestricted food intake during growth and maintenance stages was
      recorded. One group of eSMT was submitted to intermittent dietary restriction for
      5 weeks after weaning, followed by ad libitum food availability. A second group
      was restricted until one year of age. Weights and glycemic profiles were measured
      at periodic intervals. RESULTS: During the growth stage, eSMT showed weight
      increases higher than the eSS with similar food intake. In the maintenance stage,
      eSMT reached higher biomass with less intake. Post-weaning alternate restriction
      induced a slower growth pattern and lower adult weight. After five months of
      fasting, glycemia was normal (85 +/- 12 mg/dl) and controls showed altered values
      (119 +/- 14 mg/dl). Ad libitum nutrition after restriction resulted in glycemia
      levels compatible with diabetes (163 +/- 25 mg/dl) and a weight gain 75% higher
      than in ad libitum-fed animals. CONCLUSIONS: Prolonged hunger-satiety alternation
      induced slowing of the eSMT metabolopathy, whereas refeeding was associated with
      higher increases of weight and glycemia. This was imputed to an augmented
      conversion efficiency caused by fasting. These results emphasize the importance
      of understanding the relations between growth, feeding and diabetes.

PMID- 16433172
TI  - [Obtention, purification and characterization of IgY polyclonal antibodies,
      developed in hens, directed against Colombian isolates of Giardia duodenalis].
AB  - INTRODUCTION: The development of polyclonal antibodies requires laboratory
      animals, as the usually rabbits, which are bled for obtaining the
      immunoglobulins. Hens are an alternative to developing IgY polyclonal antibodies.
      OBJECTIVE: In the current study, hens were used to develop IgY anti-Giardia
      duodenalis antibodies and to evaluate five protocols for its purification.
      MATERIALS AND METHODS: Three hens were immunized intramuscularly immunized with
      Colombian Giardia duodenalis isolates trophozoites on day 0, 15, 30, 45, 60, 90
      and 120. The hen eggs were collected before each immunization, and IgY purified
      from yolk by delipidation (D) and precipitation (P) using five different
      protocols: M1: (P: ammonium sulfate/D:dextran sulfate-calcium chloride), M2: (D:
      dextran sulfate-calcium chloride/P: ammonium sulfate), M3: (D: chloroform/P:
      ammonium sulfate 50%), M4: (D: solution A/P: solution B) and M5: (D:
      chloroform/P: ammonium sulfate 30%). The immunochemistry evaluation of IgY anti
      Giardia duodenalis was assayed by immunodiffusion, counterimmunoelectrophoresis
      (CIE) and Western blot. The purity of IgY was assayed by SDS-PAGE under reducing
      and nonreducing conditions. Immunoglobulin concentration (mg/mL) was estimated by
      spectrophotometry and densitometry. RESULTS: IgY anti-Giardia duodenalis by CIE
      had titres up to 1:32. SDS-PAGE, without 2-mercaptoethanol showed a 180 kd band
      characteristic of the whole to IgY and, with 2-mercaptoethanol, two bands of 68
      and 30 kd, characteristic of its light and heavy chains, respectively. The
      greatest concentrations of immunoglobulin were recovered by method two (M2),
      producing 4.6 mg of IgY per mL of initial egg yolk. CONCLUSIONS: The easy and
      inexpensive production of IgY anti-Giardia duodenalis in hens is an advantage for
      using it to develop immunoassays that detect the parasite in fecal eluates.

PMID- 16433173
TI  - [Demographic and epidemiologic changes in Colombia during the 20th century: facts
      and explanations].
AB  - INTRODUCTION: Research, education, organization and administration activities in
      health need an updated panoramic view of demographic and epidemiologic changes
      and tendencies. OBJECTIVES: To describe the main changes in demography and
      epidemiology during the 20th century in Colombia and to comment on the causative
      models used by some authors. MATERIALS AND METHODS: A descriptive and
      longitudinal study. Second hand information from various sources was used. The
      final section of the review includes a discussion on the interpretation of data
      given by the original authors. RESULTS: In 1905-2005, population increased from
      4,737,588 inhabitants to 48,864,013. The age distribution of the population
      showed dramatic changes: the true pyramid, as seen in 1951, changed into a
      distorted figure (no apparent differences between 0 and 14 years of age). Both
      children and youngsters lost representation on age structure, while adult and
      older individuals gain representation. During 1905-1938, the birth rate was 43%
      and by the end of 2005 it will be 22%. Mortality dropped a 75%, falling from 23%
      in 1905-1912 to 6% in 1885-1993, but it rose a 33% after 1993, and will reach
      8.3% in 2010. In 1938, the urban population was 31% and in 2002, 72%. Mortality
      discriminated by cause changed in a significant manner during the second half of
      the 20th century. Infectious-parasitic and perinatal diseases, the main cause of
      death by the end of the 1960-1969 decade, lost importance on behalf of
      degenerative diseases, accidents and homicides which are now the most frequent.
      Conclusions. Our present population density is relatively low. The demographic
      change has been profound but the velocity has been more important. The aging of
      population has serious implications for the country. These notable modifications
      in Colombian families raise challenges in all social fields. The demographic and
      epidemiological changes (structure and level of morbimortality) require a serious
      analysis, and easy explanations do not have to be accepted without repairs.

PMID- 16433174
TI  - [Genetic polymorphism of Malassezia spp. yeast isolates from individuals with and
      without dermatological lesions].
AB  - INTRODUCTION: Malassezia spp. yeasts are opportunistic and newly emergent
      diseases. One or more species have been isolated in association with
      dermatological pathology and systemic disease. Their pathological role has not
      been fully elucidated since Malassezia spp. are common in normal skin flora.
      OBJECTIVE: In the current study, a search was undertaken for genetic markers in
      the Malassezia spp. isolates that correlate with each type of dermatologic
      lesion. MATERIALS AND METHODS: A total of 103 strains of Malassezia spp were
      isolated from patients with pytiriasis versicolor, seborrheic dermatitis,
      seborrheic dermatitis HIV (+), and atopic dermatitis, as well as from healthy
      individuals. Eight isolates from CBS Centraalbureau voor Schimmelcultures
      (Netherlands) were used as controls. Fingerprinting was done using random
      amplification of polymorphic DNA technique (RAPD) with three primers (OPA2, OPA4,
      OPA13). The data were analyzed with Diversity Database and SYN-TAX-PC programs.
      RESULTS: Intraspecies genetic heterogeneity in M. furfur, M. globosa, M.
      restricta, M. slooffiae, M. obtusa was observed, whereas M. sympodialis showed
      the greatest homogeneity. CONCLUSION: The dermatological disease caused by these
      different species was not associated with distinctive RAPD fingerprints.

PMID- 16433175
TI  - [Evaluation of the ELISA method for diagnosis of human cysticercosis in an
      endemic region].
AB  - INTRODUCTION: Cysticercosis is a worldwide public health problem. Currently it is
      diagnosed by detection of specific antibodies or by imaging techniques.
      OBJECTIVE: To evaluate an alternative diagnostic tool, a simple antibody
      detection assay, called Dot ELISA, for immunological diagnosis of patients with
      neurocysticercosis as well as for endemic population screening. MATERIALS AND
      METHODS: The test was applied to cysticercosis patients, as well as to healthy
      controls and individuals with other parasitic infections. A total of 45 serum, 41
      plasma and 23 cerebrospinal fluid samples were obtained from patients meeting
      clinical, surgical, imaging and laboratory criteria for cysticercosis. Samples
      were processed by enzyme-linked immune-electro-transfer blot assay and by Dot
      ELISA. Controls included 37 serum, 64 plasma and 17 cerebrospinal fluid samples
      from healthy individuals without epidemiological history for taeniosis
      cysticercosis. Similarly, 43 plasma samples from patients with parasitic
      infections different from cysticercosis and 663 samples from population survey
      for cysticercosis were also evaluated. RESULTS: A total of 933 samples were
      analyzed. In samples from cysticercosis patients and healthy control individuals,
      the Dot ELISA test showed an overall sensitivity of 80.7% (CI 95% = 80.2%-81.2%)
      and a specificity of 92.4% (CI 95% = 91.9%-92.8%). The Dot ELISA performed in
      serum had a sensitivity of 91.1%, in plasma 85.4%, and in cerebrospinal fluid
      52.2%. Similarly, the same test performed in serum, plasma and cerebrospinal
      fluid, had a specificity of 100%, 85.9% and 100% respectively. The Dot ELISA was
      applied as a screening test for the diagnosis of cysticercosis in an endemic
      population in which 1.8% (12/663) of individuals had T. solium antibodies
      detected by Enzyme-linked immune-electro-transfer blot assay and showed a
      sensitivity of 58.3% (CI 95% = 54.0-62.7) and a specificity of 100% (CI 95% =
      99.9-100.0) with a positive predictive value of 100% and a negative predictive
      value of 99.2%. All 43 samples from patients with parasitic infections different
      from cysticercosis were negative for both tests. CONCLUSIONS: These results
      indicated that Dot ELISA is a promising tool for the diagnosis of cysticercosis
      as a screening test, as well as for field epidemiological studies.

PMID- 16433176
TI  - [Purification of IgY against Salvia bogotensis lectin].
AB  - INTRODUCTION: Egg yolk immunoglobulins (IgY) have been extensively used in
      immunology, biochemistry, and biotechnology in studies of human and animal
      health. However, their use requires two preparatory steps: first, the egg yolk
      lipids must be removed without impairing the immunoglobin functional properties,
      and second, the isolation methods must allow high recoveries for further use as
      detection and purification tools. OBJECTIVE: Because Tn antigen presence serves
      as a tumoral marker and because S. bogotensis lectin's can specifically recognize
      this antigen, the current study aims at making available an anti-lectin IgY. This
      tool will be useful in histochemical and cellular studies involving transformed
      cells. MATERIALS AND METHODS: Anti-lectin IgY was produced by immunization of
      hens with S. bogotensis lectin, and the effect of antigen dose on IgY levels was
      assesed. Several methods for lipid removal, IgY extraction and purification were
      assayed, and yields and purity of IgYs were established for each method. RESULTS:
      The best delipidation and extraction method included yolk dilution with water
      under acidic conditions and (NH4)2SO4 60% s precipitation from which 43 mg
      protein/yolk were recovered. Among the chromatographic methods, thiophilic
      chromatography permitted the recovery of a substantial quantity of pure IgY (10.4
      mg IgY/yolk). With this method, the function and characteristics of IgY were
      preserved. CONCLUSION: The best conditions for anti-S. bogotensis functional IgY
      extraction and purification were established.

PMID- 16433177
TI  - [Detection of Chlamydia pneumoniae in human aortic tissue: kdtA gene
      amplification and in vitro hybridization].
AB  - INTRODUCTION: Atherosclerosis is the main cause of coronary and cerebrovascular
      disease which, in turn, are the most common causes of mortality and morbidity in
      the western world. Recent publications suggest that infective microorganisms may
      play an important role in the genesis and progression of atherosclerosis.
      According to seroepidemiological and direct detection reports, Chlamydia
      pneumoniae is the most plausible candidate. Nevertheless, the mechanisms by which
      the microorganism induces its pathological effect have not yet been conclusively
      determined; hence, the need exists to explore different detection techniques of
      C. pneumoniae on arteries. OBJECTIVE: The purpose of the current study was to
      detect the presence of C. pneumoniae in aortic tissue samples from 14 patients
      submitted to aortic replacement surgery. Detection method involved kdtA gene
      amplification coupled with an in vitro hybridization assay. MATERIALS AND
      METHODS: Samples of aortic tissue for DNA extraction and C. pneumoniae detection
      by PCR-in vitro hybridization were randomly obtained from each of 14 aorta
      specimens. RESULTS: C. pneumoniae was detected in 12 (85.7%) of the 14 aortic
      tissue samples. CONCLUSIONS: This result indicates a frequent association of C.
      pneumoniae with aortic tissue disease. Further studies are required to determine
      if this proportion of positive samples persists within larger samples.

PMID- 16433178
TI  - [Social factors associated with the daily cigarette smoking among middle-school
      student adolescents in Bucaramanga, Colombia].
AB  - INTRODUCTION: Daily cigarette smoking is associated with high morbidity and
      mortality in adults. This pattern of tobacco use is established during the early
      adolescence. Among adolescents, daily cigarette smoking is a strong predictor of
      illegal, addictive substance use. The prevalence of daily cigarette smoking is
      not known in Colombian adolescent middle-school students. OBJECTIVE: To assess
      smoking prevalence, daily cigarette smoking and associated factors among middle
      school-students in Bucaramanga, northeast Colombia. MATERIALS AND METHODS: An
      anonymous questionnaire concerning illegal and legal substance use was
      administered to a random sample of 2,586 students. RESULTS: The group mean age
      was 13.0 years; 54.9% was male; 32.0% was in sixth grade, 31.7% in seventh, 25.2%
      in eighth and 11.1% in ninth grade, with 67.1% enrolled in public schools. The
      prevalence of daily cigarette smoking lasting the month prior to the
      questionnaire was 3.8% (95% CI 2.7-4.9). Logistic regression showed a significant
      association between being the best friend of a smoker or a drinker of alcohol
      (OR=3.71; 95% CI 1.71-8.04), having low academic performance perception (OR=3.83;
      95% CI 1.0-14.2), and being older age (OR=1.4; 95% CI 1.2-1.8). CONCLUSIONS:
      These data demonstrated that one in 26 middle-school student adolescents from
      Bucaramanga is an everyday smoker. The most important associated factor was being
      the best friend of a smoker or a drinker of alcohol.

PMID- 16433179
TI  - [Control of Trypanosoma cruzi infection in blood donors in Colombia, 2003].
AB  - INTRODUCTION: Chagas disease is a public health problem in Latin America. Whereas
      the primary source of transmission is the insect vector, the second is by blood
      transfusion. Consequently, in Colombia, screening for trypanosomiasis has been
      obligatory for blood donors since 1995. OBJECTIVE: The effectiveness ot current
      strategies for infection control in donors was evaluated in order to estimate the
      risk of blood stock contamination with Chagas disease. The screening data came
      from the blood banks in the Program of External Evaluation in the Performance of
      Serology and the reports of the Laboratories of Public Health on confirming donor
      serology tests. RESULTS: In 2003, 482,371 units of blood were collected in all of
      Colombia. Of these, 99.9% were analyzed for anti-T. cruzi reactivity, with a
      positives of 0.42% detected. The Casanare Province presented the biggest number
      of reactive donors 107/1487 (7.2%), with 75 confirmed positive. In the Program of
      External Evaluation in the Performance of Serology, 45.5% of all banks
      participated-all used ELISA for screening of anti-T. cruzi. 1.1% false positives
      and nofalse negatives were indicated in 12 provinces, where 338,563 units were
      analyzed for anti- T.cruzi, 1298 units were reactive and 1108 (85.4%) were
      confirmed by the IFI test. This indicated a rate of Chagas positives of 0.33%.
      CONCLUSIONS: Although the analysis covered arrived at 99.9% of the blood units, a
      small degree of infection risk for T. cruzi still remains. The cases of T. cruzi
      in donors oscillate between 0 and 50 per thousand. This rate is highest in
      Casanare with a concomitantly high risk for acquisition of transfusional Chagas.
      ot show negative false results.

PMID- 16433180
TI  - [Impact of a UV education program on the knowledge and behavior in elementary
      school children].
AB  - INTRODUCTION: Colombians are exposed year round to high doses of ultraviolet
      radiation. Although no reliable epidemiological data are available for the
      incidence of skin cancer, it is a frequent pathology not limited to advanced age
      classes. OBJECTIVE: The current study was done at elementary schools in Cali in
      zones categorized at socioeconomic levels 1 to 4 to evaluate the impact of a
      photo-education program for its effect on the knowledge and behavior of a group
      of elementary school children. MATERIALS AND METHODS: Five hundred forty-seven
      children from kindergarten to grade three were evaluated in 4 schools categorized
      in socioeconomic levels 1 to 4. The students were interviewed to evaluate their
      knowledge and behavior with regard to effects of UV exposure. One school rated at
      level 1-2 and one school at level 3-4 received education on UV protection. Other
      two schools, rated at levels 1-2 and 3-4 each received no education on UV
      protection. The questionnaire was repeated in the 4 schools, and a statistical
      analysis was done to evaluate the impact the education program had on educated
      and control groups. RESULTS: The children that received the education program
      showed statistically significant improvement in behavior and knowledge. The
      education was more effective in low socioeconomic level populations. CONCLUSIONS:
      Follow-up studies are required to evaluate how knowledge persists over time. The
      need of a public health campaign to educate children in skin cancer prevention is
      evident.

PMID- 16433181
TI  - [Is the glabellar reflex a component of neuroleptic-induced Parkinsonism?].
AB  - INTRODUCTION: Some neurological findings have been attributed to neuroleptics as
      secondary manifestations of psychotic disorders. OBJECTIVE: In the current study,
      the role of the glabelar sign was evaluated as a clinical component of the
      secondary parkinsonism induced by neuroleptics. MATERIALS AND METHODS: Patients
      with psychosis having secondary parkinsonism induced by neuroleptics were
      evaluated with the Simpson-Angus Rating Scale for extrapyramidal side effects.
      The contribution of the glabelar syndrome in the overall syndrome was evaluated
      using factor analysis methods. RESULTS: One hundred three patients having
      secondary parkinsonism induced by neuroleptics were evaluated. The sample had
      nearly equal gender representation: with 52.4% women. A majority of patients had
      received haloperidol as antipsychotic treatment. Bipolar disorders and
      schizophrenia were the most frequent diagnostic groups. The item corresponding to
      glabelar sign showed the lower average inter item covariance and the higher
      uniqueness score. Cronbach alpha scores increased when the item corresponding to
      glabelar sign was retired from the scale. CONCLUSIONS: These results suggested
      that glabelar sign measures a condition different from secondary parkinsonism
      induced by neuroleptics. This clinical finding is not recommended for evaluating
      the evolution of neurological response to neuroleptics, however.

PMID- 16433182
TI  - [Reduction of HIV mother-to-child transmission in Colombia, two years of
      experience, 2003-2005].
AB  - INTRODUCTION: A national initiative on reduction of HIV mother-to-child
      transmission is being implemented since 2003 in Colombia, including HIV counseled
      and voluntary testing as part of the routine antenatal care, comprehensive care
      with ARV treatment to HIV-positive pregnant women and their infected children,
      caesarian delivery, and replacement of breast milk. OBJECTIVE: To describe the
      achievements in the implementation of the prevention strategy of mother-to-child
      HIV transmission, 2003-2005. MATERIALS AND METHODS: The implementation procedures
      of the Project are described, as well as the coverage percentages achieved, the
      prevention of vertical transmission and its associated factors, and the six-month
      prevalence by geographical departments. The probability of transmission adjusted
      to the ARV treatment offered and the differences by regions are also analyzed.
      RESULTS: The Project was implemented in 757 municipalities (68%); diagnostic
      tests were performed to 200,853 pregnant women, 377 of whom were diagnosed as HIV
      positive (0.19%), with higher prevalences in the Caribbean region, and in the
      Departments of Quindio and Santander. Complete six-month follow-up after delivery
      was provided to 285 women and their neonates (12 of whom were HIV-positive). The
      probability of transmission with the use of ARV schemes during pregnancy (n=170)
      was 1.78% (IC 95%: 0.37-5.13%). Factors related to probability of transmission
      were: initial viral load > 10,000/mm3, absence of antenatal care, and late
      recruitment of pregnant women. No statistical differences were found between the
      ARV schemes used. In the Caribbean region, antenatal care was lower, and late
      recruitment of pregnant women was higher. CONCLUSIONS: Reduction of HIV mother-to
      child-transmission is an effective preventive intervention, which also
      strengthens the quality of antenatal care services. Sustainability of this
      initiative, with nationwide coverage, must be a target for national and regional
      public health authorities, and for health care providers.

PMID- 16433183
TI  - [Triatomines (Reduviidae: Triatominae) in a Chagas disease focus in Talaigua
      Nuevo (Bolivar, Colombia)].
AB  - INTRODUCTION: The epidemiological importance and ecological characteristics of
      triatomines were investigated in a Chagas disease focus in Talaigua Nuevo,
      Bolivar Province. OBJECTIVE: To describe and correlate the ecological
      characteristics of triatomines in a Chagas disease focus. MATERIALS AND METHODS:
      Triatomines were collected in 300 domiciles located in the urban zone of Talaigua
      Nuevo. This included inspection of microhabitats in and around the domestic
      environment, and also wine palms, woodpiles and firewood. RESULTS: Among the 103
      triatomines collected, four species were identified--Triatoma maculata, Eratyrus
      cuspidatus, Panstrongylus geniculatus, and Rhodnius prolixus. T. maculata was the
      most abundant species (92.23%). The majority (93%) were collected in the
      intradomiciliary environment. CONCLUSION: Individuals of T. maculata naturally
      infected with Trypanosoma were recorded for the first time in Bolivar Province.
      The distribution range of P. geniculatus and R. prolixus was expanded. Using a
      multiple correspondence analysis, no relationship was discerned between the house
      type and occurrence of triatomines.

PMID- 16433184
TI  - [Vancomycin-resistant Staphylococcus aureus].
AB  - The evolution and molecular mechanisms of vancomycin resistance in Staphylococcus
      aureus were reviewed. Case reports and research studies on biochemestry, electron
      microscopy and molecular biology of Staphylococcus aureus were selected from
      Medline database and summarized in the following review. After almost 40 years of
      successful treatment of S. aureus with vancomycin, several cases of clinical
      failures have been reported (since 1997). S. aureus strains have appeared with
      intermediate susceptibility (MIC 8-16 microg/ml), as well as strains with
      heterogeneous resistance (global MIC < or =4 microg/ml), but with subpopulations
      of intermediate susceptibility. In these cases, resistance is mediated by cell
      wall thickening with reduced cross linking. This traps the antibiotic before it
      reaches its major target, the murein monomers in the cell membrane. In 2002, a
      total vancomycin resistant strain (MIC > or =32 microg/ml) was reported with vanA
      genes from Enterococcus spp. These genes induce the change of D-Ala-D-Ala
      terminus for D-Ala-D-lactate in the cell wall precursors, leading to loss of
      affinity for glycopeptides. Vancomycin resistance in S. aureus has appeared; it
      is mediated by cell wall modifications that trap the antibiotic before it reaches
      its action site. In strains with total resistance, Enterococcus spp. genes have
      been acquired that lead to modification of the glycopeptide target.

PMID- 16433185
TI  - [Genetic diversity of Plasmodium falciparum and its implications in the
      epidemiology of malaria].
AB  - Genetic diversity provides Plasmodium falciparum with the potential capacity of
      avoiding the immune response, and possibly supporting the selection of drug or
      vaccine resistant parasites. These genetic characters play key roles in the
      selection of appropriate malaria control measures. Diverse clones of Plasmodium
      falciparum, often denoted as strains, has been documented, and the degree of
      genetic diversity supported by several kinds of PCR (polymerase chain reaction)
      assays. Many studies in different endemic regions with differences in their level
      of disease transmission have clarified the interactions between the parasite
      populations and malaria epidemiology. This paper describes recombination events
      of the malaria parasite life cycle that originate such genetic diversity in P.
      falciparum, reviewing different studies on this aspect and its implications in
      the immunity and development of control measures in regions with different
      degrees of endemicity.

PMID- 16433186
TI  - [Permeability to phi chi 174 bacteriophages in polyolephin membrane condoms].
AB  - Membranes used for the manufacture of condoms eventually can develop tiny pores,
      thereby decreasing dramatically their effectiveness as a physical barrier against
      the transmission of infectious agents. A technique was designed that was based on
      the ability of bacteriophage viruses to trespass membranes and to infect certain
      bacteria species, and then developing lysis plaques in the colonies of the host
      bacteria. The effectiveness of 60 polyolefin condoms in preventing the diffusion
      of the bacteriophage phi chi 174(ATCC13706-B1), 27 nm diameter, was compared to
      20 latex condoms. Physiological conditions such as pressure, pH, superficial
      tension, length, time of exposure and viral titre were simulated. A
      pressurization system was designed, in which compressed air was injected
      simultaneously to ten condoms. Four of the 60 polyolefin condoms and one of the
      20 latex condoms were permeable to the virus. Therefore, at least 93% of the
      condoms evaluated were able to contain the virus. The difference in permeability
      between the two types of membranes was not statistically significant (P = 0.79).

PMID- 16433187
TI  - Modeling the tripartite drug efflux pump archetype: structural and functional
      studies of the macromolecular constituents reveal more than their names imply.
AB  - It is a remarkable age in molecular biology when one can argue that our current
      understanding of a process is influenced as much by structural studies as it is
      by genetic and physiological manipulations. This statement is particularly
      poignant with membrane proteins for which structural knowledge has been long
      impeded by the inability to easily obtain crystal structures in a lipid matrix.
      Thus, several high-resolution structures of the components comprising tripartite
      multidrug efflux pumps from Escherichia coli and Pseudomonas aeruginosa are now
      available and were received with much acclaim over ever-evolving crystal
      structures of soluble, aqueous proteins. These structures, in conjunction with
      functional mutagenesis studies, have provided insight into substrate capture and
      binding domains and redefined the potential interactions between individual pump
      constituents. However, correct assembly of the components is still a matter of
      debate as is the functional contribution of each to the translocation of drug
      substrates over long distances spanning the Gram-negative cell envelope.

PMID- 16433188
TI  - Antimicrobial spectrum and potency of dalbavancin tested against clinical
      isolates from Europe and North America (2003): initial results from an
      international surveillance protocol.
AB  - Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative
      possessing an extended serum elimination half-life in humans that allows once
      weekly dosing for the therapy of Gram-positive infections. Strains from this
      baseline surveillance protocol in North America (NA; USA and Canada) and Europe
      (EU, 14 countries) were sampled in 2003. A total of 7,765 Gram-positive isolates
      (3,695 from NA and 4,070 from EU) were tested by reference broth microdilution
      methods against dalbavancin and 10 comparator agents. Species were analyzed
      separately by resistance phenotypes such as methicillin- (oxacillin-) resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and
      penicillin-resistant Streptococcus pneumoniae. Dalbavancin and other
      glycopeptides were very active against staphylococci (n=4648) with dalbavancin
      being 16- to 32-fold more potent than vancomycin (MIC90, 0.06 versus 2 mg/L).
      MRSA rates were greater (31.6%) in NA than in EU (26.1%).
      Quinupristin/dalfopristin resistance (MIC, > or = 2 mg/L; 0.1-0.5%) was
      documented more often in EU compared to NA. Dalbavancin (MIC50, 0.03-0.06 mg/L)
      was active against enterococci, except VanA resistance phenotypes. VRE rates were
      lower in EU (8.3%) then in NA (35.9%) from this resistance-enhanced enterococcal
      collection. Streptococci (dalbavancin MIC90, 0.016-0.03 mg/L) were generally most
      susceptible to glycopeptides (100.0%), quinupristin/dalfopristin (98.6-100.0%)
      and linezolid (100.0%); but dalbavancin was 16-fold more active than comparators.
      All vancomycin-susceptible enterococci and > 90% of vanB VRE had dalbavancin MIC
      values at < or = 1 mg/L,but vanA VRE strains had dalbavancin MIC results ranging
      from 0.06 to > 8 mg/L (median MIC, > or = 8 mg/L). Dalbavancin MIC values were
      not adversely influenced by geographic region or resistance phenotype (except
      vanA VRE). Infrequently isolated Gram-positive organisms such as Bacillus spp.
      (MIC90, 0.12 mg/L), Corynebacterium spp. (MIC90, 0.12 mg/L), Listeria
      monocytogenes (MIC90, 0.25 mg/L) and Micrococcus spp. (MIC90, 0.03 mg/L) were
      very susceptible to dalbavancin. In conclusion, these 2003 baseline resistance
      surveillance findings confirm the potent dalbavancin activity compared to several
      comparator agents against important Gram-positive pathogens. This high volume
      international survey indicates potential therapeutic roles for dalbavancin
      against many troublesome resistant Gram-positive phenotypes.

PMID- 16433189
TI  - Prevalence and clinical management of complicated urinary tract infections in
      Italy: a prospective multicenter epidemiological study in urological outpatients.
AB  - The objectives of the study were to evaluate the prevalence of complicated
      urinary tract infections among Italian patients attending the urologist's office,
      to describe the frequency of different complication factors, the encountered
      bacterial pathogens and the clinical attitude of urologists in management of
      complicated urinary tract infections (CUTIs). The study was a prospective,
      multicenter study which was undertaken by office urologists throughout Italy.
      During the May-June 2002 timeframe, the prevalence of each urologist's diagnosis
      of CUTIs was noted for a 4-week slot. The prevalence of CUTIs in over 13,000
      patients observed was 10.8% (n = 1201), with a trend (not statistically
      significant) of higher figures in the South/Islands (12.2%) with respect to
      Center (11.4%) or North (8.7%) of Italy. We have confirmed the significant
      relevance of CUTI among the Italian patients attending the urologist office and
      the clinical data collected may contribute to improve the diagnosis and empiric
      therapy of complicated urinary tract infections.

PMID- 16433190
TI  - In vitro activity of linezolid and other antibiotics against Gram-positive
      bacteria from the major teaching hospitals in Kuwait.
AB  - Multidrug-resistant Gram-positive bacteria are an increasingly pressing problem
      in the clinic. Consequently, linezolid, a recently introduced oxazolidinone with
      Gram-positive activity, was tested in comparison with 10 other antibiotics
      against 8103 clinically significant Gram-positive cocci by Etest, disk diffusion
      and Vitek methods. Linezolid demonstrated excellent activities against all
      isolates. Vancomycin and teicoplanin demonstrated equally excellent activity
      against almost all isolates. The methicillin-resistant Staphylococcus aureus
      (MRSA) strains were all susceptible to the glycopeptides and linezolid, but
      resistant to erythromycin (96%), fusidic acid (91.5%), gentamicin (84%) and
      clindamycin (73%). Forty one and 39% of the Streptococcus pneumoniae isolates
      were resistant to penicillin (MIC >0.5 microg/ml) and erythromycin (MIC >1
      microg/ml), respectively. S. agalactiae susceptibility was 9% and 10% resistant
      to clindamycin and erythromycin, respectively. In conclusion, all the Gram
      positive isolates tested were susceptible to linezolid. With its oral
      bioavailability profiles, it obviously holds great promise. Our data should be a
      useful addition to the literature from the Middle East.

PMID- 16433192
TI  - In vitro activity of beta-lactam antimicrobial agents in combination with
      aztreonam tested against metallo-beta-lactamase-producing Pseudomonas aeruginosa
      and Acinetobacter baumannii.
AB  - We evaluate the antimicrobial interactions between aztreonam and selected beta
      lactams when tested against metallo-beta-lactamase (MbetaL)-producing clinical
      strains. Ten Pseudomonsa aeruginosa strains, including nine MbetaL-producers (IMP
      1, -2, -13, -16, VIM-1, -2, -7, SPM-1 and GIM-1) and five Acinetobacter baumannii
      strains, including three MbetaL-producers (IMP-1 and -2) were tested using time
      kill/bactericidal activity methods. Aztreonam at 4, 8 and 16 mg/L was combined
      with four other beta-lactam antimicrobials (cefepime, ceftazidime, meropenem and
      piperacillin/tazobactam or ampicillin/sulbactam), each tested at the recognized
      susceptible breakpoint concentration. Enhanced activity (synergism or additive
      effect) was observed with four P. aeruginosa strains (IMP-16, VIM-2, SPM-1 and
      GIM-1 containing strains) and four A. baumannii strains, while antagonism was
      observed with two P. aeruginosa (IMP-16 and SPM-1-producing strains) and one A.
      baumannii (non-MbetaL) strain. All other strains showed indifferent interaction
      (variation of +/- 1 log10 CFU/ml) with any combination evaluated.

PMID- 16433191
TI  - Evaluation of in vitro interaction of daptomycin with gentamicin or beta-lactam
      antibiotics against Staphylococcus aureus and Enterococci by FIC index and timed
      kill curves.
AB  - The interactions of daptomycin with gentamicin and 5 beta-lactam agents were
      determined by checkerboard and timed-kill studies. Eighty isolates were tested by
      checkerboard: 20 each of methicillin-resistant Staphylococcus aureus (MRSA),
      methicillin-susceptible Staphylococcus aureus (MSSA), vancomycin-susceptible
      Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE). Time
      kill curves were performed on 8 selected isolates: 2 each of MRSA, MSSA, VSEF and
      VRE. Checkerboard results showed highest frequency of synergistic effects against
      VSEF (35-75%) with daptomycin combined with ceftriaxone, cefepime or imipenem; a
      modest effect with most combinations against VRE and MRSA (5-20%); and
      indifference with daptomycin and most agents against MSSA (0-5%); except with
      daptomycin with oxacillin where 10-20% synergy was observed. Synergistic
      interaction was confirmed by time kill studies in seven of ten isolates where
      checkerboard suggested synergy. A bactericidal effect was exerted in 5/7
      synergistic combinations. The in vitro data suggest that daptomycin combined with
      other antibiotics may be microbiologically beneficial and not antagonistic.

PMID- 16433193
TI  - Evaluation of antimicrobial treatments in children with acute otitis media in
      Spain: a pharmacokinetic-pharmacodynamic (PK/PD) approach.
AB  - Pharmacokinetic/pharmacodynamic (PK/PD) principles are priceless tools for
      evaluating the effectiveness of different antimicrobial treatments for different
      infections. However, very few studies deal with pediatric dosages and take into
      account the unbound drug serum levels. Our study is focused on the most frequent
      antibiotic dosing schedules used in Spain for the treatment of acute otitis media
      (AOM) in children, where high rates of penicillin and macrolide resistance exist
      among pneumococcal isolates. Pharmacokinetic parameters of antibiotics in
      children where obtained from the literature. The minimum inhibitory
      concentrations (MIC90) of antibiotics for pediatric strains of Streptococcus
      pneumoniae and Haemophilus influenzae were obtained from the SAUCE 2 project.
      Only ceftriaxone (50 mg/kg single intramuscular dose) and high doses of co
      amoxiclav (27-33 mg/kg q8h) provided adequate efficacy indexes (tss(%)>MIC) for
      both S. pneumoniae and H. influenzae in AOM in children. These results are
      consistent with MEF (medium ear fluid) levels obtained from the literature. Our
      results confirm the utility of serum unbound levels to predict efficacy of
      antibiotics in children with AOM.

PMID- 16433194
TI  - Clinical efficacy and safety of a short regimen of azithromycin sequential
      therapy vs standard cefuroxime sequential therapy in the treatment of community
      acquired pneumonia: an international, randomized, open-label study.
AB  - An international, randomized, open-label, comparative study was undertaken in
      order to assess the efficacy and safety of azithromycin and cefuroxime, short
      sequential vs standard sequential therapy, respectively, in the treatment of
      patients with community-acquired pneumonia (CAP). 180 adult patients were
      included in the study. 89 patients received azithromycin 500 mg intravenously
      (i.v.) once daily for 1-4 days followed by azithromycin 500 mg orally once daily
      for 3 days. 91 patients received cefuroxime 1.5 g i.v. three times daily for 1-4
      days followed by cefuroxime axetil 500 mg orally twice daily for 7 days. Clinical
      efficacy was achieved in 67/82 (81.7%) patients treated with azithromycin, and in
      73/89 (82.0%) patients treated with cefuroxime. The mean duration of total (i.v.
      and oral) therapy was significantly shorter for the azithromycin group than for
      the cefuroxime group (6.2 days vs 10.1 days). Adverse events were recorded in
      38.2% of patients treated with azithromycin, and in 29.7% of patients treated
      with cefuroxime (p = 0.20). Shorter sequential i.v.-to-oral azithromycin therapy
      of patients with CAP was as effective as standard sequential i.v.-to-oral
      cefuroxime therapy.

PMID- 16433195
TI  - The effectiveness and safety of oral linezolid for the primary and secondary
      treatment of osteomyelitis.
AB  - The pharmacokinetic profile of oral linezolid makes it an attractive alternative
      for the treatment of osteomyelitis. Few studies have described the efficacy of
      linezolid in the treatment of osteomyelitis. A retrospective, observational
      analysis was conducted at Edward Hines, Jr. VA Hospital. Patients who received
      oral linezolid from June 2000 to December 2002 were identified from pharmacy
      records. Forty-two patients who received oral linezolid for osteomyelitis at our
      institution were identified. Only patients who had received at least six weeks of
      linezolid therapy were evaluated for clinical effectiveness. Patients were also
      evaluated for adverse drug reactions due to linezolid. The clinical cure rate was
      55% for the 20 patients who received at least six weeks of therapy. Adverse
      events included gastrointestinal disturbances (15%), thrombocytopenia (10%),
      anemia (10%), neutropenia (5%) and rash (5%). The authors conclude that oral
      linezolid is an alterative to intravenous antibiotics for the treatment of
      osteomyelitis.

PMID- 16433196
TI  - Interferon alpha monotherapy for chronic hepatitis C viral infection in
      thalassemics and hemodialysis patients.
AB  - We assessed the effectiveness of interferon (IFN) monotherapy in thalassemic or
      hemodialysis patients with chronic hepatitis C viral (HCV) infection. Ten
      thalassemic and four hemodialysis patients were included in the study. Chronic
      HCV was confirmed with both serum HCV-RNA and liver histopathology. IFN alpha-2a
      was administered three times a week for 24-48 weeks, at a dose of 5 MU/m2
      (maximum 6 million units). Sustained response was defined as negative HCV-RNA at
      least 24 weeks after termination of the treatment. All patients completed the
      study. Eight of 10 thalassemic (80%) and one of four hemodialysis patients (25%)
      showed a sustained response. IFN monotherapy proved to be an effective treatment,
      especially in thalassemic patients with chronic HCV. IFN monotherapy seems
      reasonable for patients with thalassemia and chronic hepatitis C virus in whom
      ribavirin cannot be used.

PMID- 16433197
TI  - The emerging role of oxaliplatin in the treatment of gastric cancer.
AB  - Gastric cancer is often diagnosed in locally advanced or metastatic stages and,
      therefore, of poor prognosis. Many controversies exist about surgery,
      neoadjuvant, adjuvant and palliative treatments of gastric cancer. So we need to
      explore a variety of novel management options including the use of new agents and
      new combinations. Some of these agents include oral fluoropyrimidine, irinotecan,
      docetaxel and oxaliplatin. Oxaliplatin is a diaminocyclohexane-platinum compound
      that is significantly different from cisplatin and carboplatin with respect to
      its activity and toxicity. Oxaliplatin is an alkylating agent inhibiting DNA
      replication by forming adducts between two adjacent guanines or guanine and
      adenine molecules. However, the adducts of oxaliplatin appear to be more
      effective than cisplatin adducts in regard to the inhibition of DNA synthesis. In
      contrast to cisplatin, oxaliplatin has demonstrated efficacy alone and in
      combination with 5-fluorouracil in advanced colorectal cancer. Many studies are
      ongoing to test the combination in noncolorectal gastrointestinal tumors and
      other malignancies. This review focuses on the increasing amount of data
      concerning the clinical activity of oxaliplatin-based regimens in advanced
      gastric cancer.

PMID- 16433198
TI  - Idarubicin and idarubicinol effects on breast cancer multicellular spheroids.
AB  - Despite extensive preclinical evaluation in several experimental models, no
      studies have determined the effect of idarubicin and its metabolite idarubicinol
      on multicellular spheroids, a model which mimics the microregions of solid
      tumors. The principal aim of the present study was to investigate the in vitro
      cytotoxicity of idarubicin and its metabolite idarubicinol on MCF-7 breast cancer
      cells growing as monolayers or multicellular spheroids and to evaluate the
      influence of the length of exposure on the cytotoxic effect of both drugs.
      Cytoxicity was evaluated on monolayer and spheroid cultures exposed to idarubicin
      and idarubicinol 0.01-1000 ng/ml for 24 h or treated for 6, 12, 24 and 48 h to
      100 ng/ml of both drugs. The IC50 of idarubicin and idarubicinol were 3.3+/-0.4
      and 3.6+/-0.7 ng/ml, respectively, on MCF-7 monolayers and 7.9+/-1.1 and 5.3+/
      0.7 ng/ml in multicellular spheroids, respectively. The antiproliferative effects
      of 100 ng/ml idarubicin and idarubicinol on MCF-7 spheroids was characterized by
      a marked time-dependence, which was less evident on MCF-7 growing as monolayer.
      In conclusion, the present experimental data demonstrate, for the first time,
      that idarubicin and idarubicinol have significant cytotoxic activity against
      multicellular spheroids, comparable to the antiproliferative effects on monolayer
      cells. In contrast, spheroids displayed substantial resistance after short
      exposure times that was not present in the two dimensional cultures.

PMID- 16433199
TI  - Pharmacokinetics of mitomycin C after resection of peritoneal carcinomatosis and
      intraperitoneal chemohyperthermic perfusion.
AB  - Over the last few years surgery on patients with abdominal malignancies has
      become more aggressive but the majority of patients present locoregional
      recurrence as peritoneal dissemination. Cytoreductive surgery followed by
      intraperitoneal chemohyperthermic perfusion (ICHP) has been described for
      treatment and prevention of locoregional cancer spread from various origins. This
      paper reports our study of the pharmacokinetics of mitomycin C (MMC) administered
      by intraperitoneal chemohyperthermic perfusion (ICHP) in patients with peritoneal
      carcinomatosis. 28 patients received MMC 20 mg/m2 intraperitoneally as a
      perfusion over 60 min. MMC was determined in perfusate, plasma and urine samples
      with a UV-HPLC method. A compartmental model was used to fit the drug
      concentrations in plasma and perfusate. Our results showed a mean maximum plasma
      concentration (Cmax) of 0.14 +/- 0.086 microg/ml with a peak time (Tmax) of 48..7
      +/- 5.61 min. The mean area under the curve (AUC) and terminal half-life (t1/2)
      were 15.8 +/- 9.8 mg x min/L and 83.7 +/- 31.74 min respectively. Clearance (CL)
      was estimated by fitting the data by a compartmental model and the mean value was
      72 +/- 66 L/h. The percent of the dose absorbed was very variable and ranged
      between 14 and 57% (mean 37 +/- 14%). The mean percentage of dose recovered
      unchanged in the urine during 24 hours was 7.21 +/- 3.73%. We conclude that ICHP
      in patients with peritoneal surface malignancies seems to have clinical value
      since it gives high peritoneal and tumor MMC concentrations with limited systemic
      exposure and toxicity.

PMID- 16433200
TI  - Extended continuous oral temozolomide in patients with progressive metastatic
      renal cell carcinoma not responding to interferon alpha 2b.
AB  - The aim of the study was to evaluate the toxicity and efficacy of oral extended
      continuous temozolomide in patients with progressive metastatic renal cell
      carcinoma (RCC) not responding to immunotherapy after removal of the primary
      tumor. Patients with progressive metastatic RCC received protracted temozolomide
      100 mg/m2 orally on days 1-21 every 28 days. Response was assessed after 2 cycles
      to be followed by another 2 cycles in the absence of progression. After 4 cycles
      only patients with further remission and acceptable toxicity were to continue. No
      objective responses were observed in 12 patients and the trial was stopped
      prematurely in stage 1. Six patients remained stable during 4 cycles of
      temozolomide (4 months), only one of these remained stable for another 2 months
      after having stopped treatment. Five patients progressed after the initial 2
      cycles and one after the first cycle. Overall survival was 15.5 months (range 1
      36 months). Repeated cycles of 3 weeks oral temozolomide 100 mg/m2 followed by
      one week rest proved tolerable though this regimen may only have limited activity
      against metastatic RCC.

PMID- 16433201
TI  - Gefitinib treatment is highly effective in non-small-cell lung cancer patients
      failing previous chemotherapy in Taiwan: a prospective phase II study.
AB  - Gefitinib has shown activity in the treatment of non-small-cell lung cancer
      (NSCLC) patients who failed previous platinum-based combination chemotherapy
      and/or taxane treatment. Recently, gefitinib was documented to be more effective
      in an East Asian population, as well. Thus, we performed a gefitinib trial in
      Taiwanese patients to assess the efficacy of this regimen. Treatment consisted of
      gefitinib 250 mg one tablet daily until disease progression. Thirty-six patients
      were enrolled from January 2003 to September 2004. Gefitinib was second-line
      treatment in 10, third-line in 15, fourth-line in 9, and fifth-line in 2. All
      patients were evaluable for toxicity profile and response rate. After 8 weeks of
      treatment, three patients had a complete response (CR) and nine had a partial
      response (PR), with an overall response rate of 33.3% (95% confidence interval
      17.9%-48.7%). All treatment-related toxicities were few and mild in severity,
      except that one patient suffered from reversible grade 3 interstitial
      pneumonitis. The median time to disease progression was 4.7 months, and the
      median survival was 9.5 months. The one-year survival rate was 45.1%. Survival
      was significantly better in those who responded to treatment (CR and PR) than in
      those who did not (median 20.1 vs. 4.7 months, p=0.0002). Survival was also
      better in those who demonstrated disease control using gefitinib (CR, PR, and
      stable disease) than in those who did not (14.1 vs. 1.4 months, p<0.0001). The
      authors conclude that daily gefitinib treatment has high activity, is well
      tolerated, and provides very good survival in Taiwanese NSCLC patients who have
      failed previous chemotherapy, especially in those who responded to gefitinib
      treatment or those whose disease was controlled by gefitinib treatment.

PMID- 16433202
TI  - Gemcitabine and cisplatin in the treatment of elderly patients with advanced non
      small cell lung cancer: impact of comorbidities on safety and efficacy outcome.
AB  - The aim of the study was to describe in detail the impact of aging and
      comorbidities on safety and efficacy of gemcitabine-cisplatin in the subset of
      elderly with advanced NSCLC. We report the results of our study which enrolled
      patients aged over 65 years or older. This study included 46 patients
      consecutively admitted to our Department. Treatment consisted of gemcitabine 1250
      mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 2, of a 21-day cycle. The
      Charlson score method was chosen to evaluate the conditions of comorbidity. All
      patients were evaluable for toxicity and 44 for activity. A total of 128 courses
      were administered, with a median of 3 courses per patient and a dose-intensity of
      93% and 88% for gemcitabine and cisplatin, respectively. Grade 3-4 neutropenia
      (22% of patients) and grade 3 asthenia (4.5%), emesis (4.5%) and nephrotoxicity
      (4.5%) were the most severe adverse events. Univariate analysis of toxicity did
      not show any significant difference among all groups. The overall response rate
      was 45.6% (95% CI, 31.3-60). At a median follow up of 13 months, the median and
      progression-free survival were 15 and 8 months, respectively. The multivariate
      analysis resulted in objective response and disease control being predictive of
      longer survival. The combination of gemcitabine and cisplatin appears to be an
      effective and tolerated regimen for elderly patients with advanced NSCLC,
      regardless of aging and condition of comorbidities. Prospective randomized trials
      based on specific geriatric assessment are required to obtain compelling
      information for the optimal management of elderly patients with advanced NSCLC.

PMID- 16433203
TI  - Allergoid-specific T-cell reaction as a measure of the immunological response to
      specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine.
AB  - BACKGROUND: Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper
      cells. In order to improve safety, SIT vaccines are often formulated with
      allergoids (chemically modified allergens). Interaction between T-cells and
      allergoids is necessary to influence cellular cytokine expression. There have
      been few reports on identification the early cellular effects of SIT. METHOD:
      Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4
      shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids
      (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant,
      monophosphoryl lipid A (MPL). Fourteen grass-allergic patients served as
      untreated controls. Using the peripheral blood mononuclear cells of these
      patients, an optimized lymphocyte transformation test (LTT) was employed to
      monitor the in vitro proliferative response of T-cells to an allergoid challenge
      (solubilised Pollinex Quattro) before the first and last injection and then 2 and
      20 weeks after the final injection. Control challenges utilised preparations of a
      similar pollen vaccine without the adjuvant MPL and a tree pollen vaccine with
      and without MPL. RESULTS: The LTT showed increased LTT stimulation indices (SI)
      in 17/20 SIT patients when the solublised vaccine preparation was used as a
      challenge before the last injection and 2 weeks after, in comparison to pre
      treatment levels. Twenty weeks after therapy, the SI decreased to baseline level.
      A vaccine challenge without MPL gave lower SI levels. A challenge of a clinically
      inappropriate tree allergoid vaccine gave no response, and a nontreated group
      also showed no response. CONCLUSION: Following a short-course SIT adjuvated with
      MPL, challenges of allergoids were shown to activate allergen-specific T cells in
      vitro. There was an additional stimulating effect when the challenge was in
      combination with MPL. There were no non-specific effects of MPL, shown by the
      tree allergoid/MPL control. The timing of the response was closely correlated to
      the treatment course; reactivity fell two weeks after the final injection and 20
      weeks later it was at baseline level. Thus an immunological response to SIT was
      detected after very few injections. This methodology could provide a basis for
      monitoring the immediate progress of allergy vaccinations.

PMID- 16433205
TI  - Safety of celecoxib in patients with adverse skin reactions to acetaminophen
      (paracetamol) and other non-steroidal anti-inflammatory drugs.
AB  - BACKGROUND: Acetaminophen (paracetamol-P) is a widely used analgesic-antipyretic
      drug with no anti inflammatory effects and its rate of adverse hypersensitivity
      reactions is very low. On the contrary non-steroidal anti-inflammatory drugs
      (NSAIDs) are commonly involved in side effects. Celecoxib (CE) is a novel drug,
      with high selectivity and affinity for COX-2 enzyme. OBJECTIVE: We evaluated the
      tolerability of CE in a group of patients with documented history of adverse
      cutaneous reactions to P and to classic NSAIDs. METHODS: We studied 29 patients
      with hypersensitivity to P and classic NSAIDs. The diagnosis of P-induced skin
      reactions was based on in vivo challenge. The placebo was blindly administered at
      the beginning of each challenge. After three days, a cumulative dosage of 200 mg
      of CE in refracted doses was given. After 2-3 days, a single dose of 200 mg was
      administered. All patients were observed for 6 hours after each challenge, and
      they were controlled again after 24 hours to exclude delayed reactions. The
      challenge was considered positive if one or more of the following appeared:
      erythema, rash or urticaria-angioedema. RESULTS: No reaction was observed with
      placebo and twenty eight patients (96.5 %) tolerated CE. Only one patient
      developed a moderate angioedema of the lips. CONCLUSION: Only one
      hypersensitivity reaction to CE was documented among 29 P-intolerant patients.
      Thus, we conclude that CE is a reasonably safe alternative which can be used in
      subjects who do not tolerate P.

PMID- 16433204
TI  - Retrospective study of tolerance to short initiation schedules in subcutaneous
      immunotherapy.
AB  - With the aim of evaluating tolerance to new shorter initiation schedules in
      subcutaneous immunotherapy everyday clinical practice, a study was carried out
      using Pangramin Plus with initiation periods between 3 (Cluster) and 6 (Plus)
      weeks. All the information was processed retrospectively and both systemic (SR)
      and local (LR) adverse reactions occurring between September 2002 and February
      2003 were recorded. A total of 353 patients (261 Plus and 91 Cluster) were
      included and 2,886 doses were administered (2,166 in initiation and 720 in
      maintenance). Of these, 800 were with Grass mix extract, 1,141 Grass mix + Olea,
      273 Olea, 73 Dermatophagoides mix and 599 Dermatophagoides pteronyssinus. As
      regards adverse reactions (AR), 2.8% of patients showed SR and 4.8% LR, 1.2% of
      doses caused some type of reaction (SR and LR in 0.3% and 0.9%, respectively).
      The initiation schedule, first dose or allergens resulted in no significant
      differences in the frequency of adverse reactions. The Grass mix extract showed
      the highest frequency of AR. Sixty-seven percent of SR and 68% of LR were
      delayed. 64% of these reactions resolved spontaneously while the rest responded
      favourably to treatment. Adrenaline was administered on one occasion for
      immediate asthma. There were no cases of anaphylactic shock, hospitalisation or
      life-threatening situations. Pangramin Plus tolerance, therefore, can be
      classified as good, similar to conventional schedules, but with the benefits of
      shorter initiation schedules.

PMID- 16433206
TI  - Correlation between Chenopodiacea/Amaranthacea pollen counts and allergic
      symptoms in Salsola kali monosensitized patients.
AB  - We performed a prospective observational study to establish a relationship
      between pollen counts of Chenopodiacea/Amaranthacea and clinical symptoms of
      rhinoconjunctivitis and asthma in a group of monosensitised patients. MATERIAL
      AND METHODS: A total of 60 patients (19 with asthma) were included in the study.
      All patients collected daily symptom scores during the summer months of 1999,
      2000 and 2001. The questionnaire included ocular, nasal and pulmonary symptoms.
      Pollen counts were expressed as pollen grains/m3. Symptom scores and pollen
      counts were correlated using correlation coefficients and Log transformed
      variables. RESULTS: In the 3 seasons studied we identified a peak of pollen and
      clinical symptoms in the second half of August and first half of September. In
      1999, there was a significant positive correlation between total symptoms and
      daily pollen grains/m3 (p<0.005, r = 0.347). This correlation was not significant
      for the summers of 2000 and 2001. After further analysis, and by displacing one
      of both variables between 11 to 17 days, the correlation coefficients for total
      symptoms, improved for 1999 (r = 0. 744; p < 0.0001) and became significant for
      2000 (r = 0. 521; p < 0.0001) and 2001 (r = 0.635; p < 0.0001). CONCLUSION: We
      identified a significant time lag between pollen counts and symptom scores in S.
      kali monosensitized patients.

PMID- 16433207
TI  - Allergenic cross-reactivity between Blomia tropicalis and Blomia kulagini (Acari:
      Echymiopodidae) extracts from optimized mite cultures.
AB  - BACKGROUND: At present, data about the cross-reactivity of Blomia spp. comes from
      studies made among different genera of mites, and no results have been published
      involving different species of the genus Blomia. OBJECTIVE: The aim of this study
      was to find out the level of cross-reactivity between the two main species of
      Blomia causing allergy, and its implication in the diagnosis of Blomia
      sensitization. METHODS: Using extracts from optimal growth phases of Blomia
      kulagini (Zakhvatkin, 1936) and Blomia tropicalis (van Bronswijk, Cock and
      Oshima, 1973) as allergenic material, the allergenic cross-reactivity between
      both house dust mites was evaluated by means of cutaneous tests, specific IgE
      values, ImmunoCAP-inhibition and SDS-PAGE-IgE-immunoblotting-inhibition. RESULTS:
      The results demonstrated that IgE-binding components belonging to both species
      are very similar from the immunological point of view, showing high correlations
      between both species when using cutaneous tests (R2=0.915) or specific IgE
      (R2=0.980). ImmunoCAP-inhibition and SDS-PAGE-IgE-Immunoblotting-inhibition
      probed with human sera, showed a total inhibition of specific IgE reactions by
      the heterologous antigens. CONCLUSION: The results obtained strongly suggest the
      great resemblance between the allergenic composition of both species.

PMID- 16433208
TI  - Early decrease in nasal eosinophil proportion after nasal allergen challenge
      correlates with baseline bronchial reactivity to methacholine in children
      sensitized to house dust mites.
AB  - BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after
      allergen exposure of the membranes lining the nose which, in predisposed
      individuals, may constitute a risk factor for the occurrence of asthma.
      OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure,
      11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with
      rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr)
      were studied. METHODS: The following parameters were evaluated: i) pulmonary
      function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh;
      iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal
      allergen challenge (NAC). On NBs, the following markers of inflammation were
      evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated
      eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1
      and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children
      showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression
      (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated
      with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed
      after NAC (p=0.002) was associated with a significant decrease in the 'intact to
      degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still
      present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced
      decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM,
      experimental allergen exposure is followed by an early depletion of nasal
      eosinophils. The correlation between allergen-induced changes in nasal
      eosinophilia and bronchial reactivity to MCh further supports the concept of a
      tight link between upper and lower respiratory tract involvement in respiratory
      allergy.

PMID- 16433209
TI  - Influence of age and gender on serum eotaxin concentration in healthy and
      allergic people.
AB  - BACKGROUND: Eotaxin is one of the important chemokines that modulate allergic
      inflammation. In many studies a correlation between an elevated serum
      concentration of eotaxin, allergen exposure and allergic symptoms has been
      confirmed. Influence of other factors on eotaxin concentration is feebly
      recognized. We made an attempt to assess the influence of age and gender on the
      serum eotaxin level in healthy people and in patients with intermittent IgE
      mediated rhinoconjunctivitis (AR). METHODS: The serum eotaxin level was measured
      in 245 healthy people and 241 patients with AR before the pollen season with the
      ELISA technique (KITS, R&D USA, pg/ml). The parametric tests and linear
      regression analysis were used in statistical calculations. RESULTS: There were no
      differences between the allergic group and the healthy one in the mean age
      (accordingly: 31.3 +/- 11.6 yrs. vs. 31.6 +/- 12.5 yrs.; p=0.1) and the mean
      serum eotaxin content (118.1 +/- 44.9 pg/ml vs. 116.3 +/- 34.8 pg/ml; p=0.3). A
      significant relationship between the serum eotaxin level, gender and age was
      revealed in both groups and regression models were derived. A linear correlation
      between age (semi-partial correlation beta = 0.47, p = 0.0000001) and gender
      (semi-partial correlation beta = 0.3, p = 0.0000001), on the one side, and the
      serum eotaxin level, on the other, was found for the allergic people. In the
      control group a similar relationship between the serum eotaxin level and age
      (semi-partial correlation coefficient beta = 0.63, p = 0.0000001) and gender
      (semi-partial correlation factor beta = 0.23, p = 0.000006) was observed.
      CONCLUSIONS: Age and sex significantly influence the serum eotaxin content in
      healthy people and patients with IgE-mediated rhinoconjunctivitis.

PMID- 16433210
TI  - Double-blind, placebo-controlled study of immunotherapy with Parietaria judaica:
      clinical efficacy and tolerance.
AB  - Allergy to Parietaria causes significant morbidity in most Mediterranean areas.
      The aim of this study is to investigate the efficacy and tolerance of Parietaria
      depot extract at 25 BU/mL (1.5 microg/mL Par j 1). We performed a multicenter
      double-blind, placebo-controlled study in rhinitic patients with/without asthma,
      sensitized to Parietaria. 42 patients followed 20-month immunotherapy. Clinical
      efficacy was based on symptom and medication scores and the percentage of healthy
      days (days without symptoms or medication). Severity of asthma/rhinitis scales,
      visual analogue scale, evaluation of the treatment by doctors and patients,
      immediate and delayed cutaneous response and quality of life questionnaires were
      also studied. The active group showed a sustained decrease in symptoms (p =
      0.008), medication (p = 0.009) and both (p = 0.001), and an increase in healthy
      days (p = 0.001) throughout the study, with a threefold increase of healthy days
      and almost a three time reduction in medication only after one year of treatment.
      Asthma and rhinitis severity scales also decreased after immunotherapy, and
      blinded clinical evaluation by physicians confirmed efficacy in 85% and 77% of
      the active patients. Patient's self-evaluation returned similar results. None of
      these changes were observed with placebo. Immediate cutaneous response was
      significantly reduced at the maintenance phase in the active group and remained
      reduced throughout the study. Late-phase response after intradermal testing also
      showed a statistical decrease in actively treated patients. Immunotherapy was
      well tolerated and every systemic reaction reported was mild. In conclusion,
      immunotherapy with Parietaria 25 BU/mL is an effective and safe treatment for
      patients with respiratory allergies.

PMID- 16433211
TI  - Multiple drug hypersensitivity--proof of multiple drug hypersensitivity by patch
      and lymphocyte transformation tests.
AB  - BACKGROUND: Multiple drug hypersensitivity (MDH) was first described in 1989 by
      Sullivan et al. as drug allergies to two or more chemically different drugs. So
      far, the diagnosis of MDH was associated almost exclusively with antibiotics and
      was defined based on history alone. AIMS OF THE STUDY: The objective of this
      study was to prove MDH by two independent tests, namely patch (PT) and lymphocyte
      transformation (LTT) tests. METHODS: Here we present 7 patients matching the
      definition of a MDH which were documented by positive LTT as well as PT to
      different drugs. RESULTS: Three of the 7 patients developed sensitization to the
      different compounds during the same treatment period and had one longer-lasting
      allergic reaction. For another 4 patients sensitization to the different drugs
      occurred at distinct time points. CONCLUSIONS: Our data support the concept of a
      MDH syndrome. The multiple sensitizations can be proven by skin and in vitro
      tests. We propose two subtypes of MDH: MDH, which develops against different
      drugs given simultaneously, and a second subtype, where the sensitizations
      develop sequentially. Antibiotics are often involved, but we also found
      sensitization to antiepileptics, hypnotics, antidepressants, local anesthetics,
      corticosteroids and other drug classes.

PMID- 16433213
TI  - Hydrochlorothiazide-induced acute non-cardiogenic pulmonary edema.
AB  - We report the case of a 64 year-old male with non cardiogenic pulmonary edema
      episodes after oral administration of 12.5 mg of hydrochlorothiazide. In vitro
      immunologic study with basophil activation test and late cellular activation
      study (CD69 and production of interferon gamma) with chlorothiazide were
      performed, and no activation was observed. As a consequence, like in previous
      cases published, the pathogenic mechanism remains unknown, and it probably is an
      idiosyncratic reaction.

PMID- 16433212
TI  - Immunological studies in a case of hydrochlorothiazide-induced pulmonary edema.
AB  - A case of acute onset non-cardiogenic pulmonary edema induced by
      hydrochlorothiazide (HCT) is presented. Rapid recovery was obtained with
      supportive therapy. Leukopenia was evident during the acute phase, with rapid
      recovery parallel to the clinical improvement, suggesting pulmonary sequestration
      of granulocytes. Immunological studies including lymphocyte stimulation test with
      HCT and measurement of specific IgG and IgE to HCT elicited negative results. The
      pathogenesis of this type of reaction remains to be elucidated.

PMID- 16433214
TI  - Delayed selective reaction to clavulanic acid: a case report.
AB  - Clavulanic acid, an inhibitor of beta-lactamases, is widely used for
      antimicrobial therapy in association with beta-lactam antibiotics. Despite this,
      very few adverse reactions to the molecule have been described so far. We report
      a case of not-immediate reaction to clavulanic acid in a young adult who
      previously tolerated it. The patient complained of generalized itchy erythema two
      days after completing a course of amoxicillin-clavulanate therapy, and had no
      previous clinical history of adverse reactions to drugs. Intradermal and skin
      prick tests with beta-lactam determinants were negative, as well as the oral
      tolerance test with amoxicillin. Since no commercial preparation of clavulanic
      acid alone is available, we performed intradermal and skin prick test with the
      association amoxicillin-clavulanate, that elicited a delayed (24 and 48 hours)
      response. IgE-mediated reactions to clavulanic acid are rare, since this molecule
      is poorly allergenic. Based on the onset time and the specificity of the response
      we hypothesize that a delayed (possibly T-cell mediated) reaction has occurred.

PMID- 16433215
TI  - Ultrarush immunotherapy in a patient with occupational allergy to bumblebee venom
      (Bombus terrestris).
AB  - Bumblebee venom allergies, though uncommon among the broad public, pose a
      significant risk in plant industry and scientific occupation. Since a significant
      IgE cross-reactivity between bumblebee and honeybee venom has been described in
      several cases and bumblebee venom for immunotherapy has been available only from
      a few suppliers, SIT with honeybee venom was frequently used for bumblebee venom
      allergic patients in the past. We present the case of occupational bumblebee
      allergy in a biologist who developed anaphylactic reactions with subsequent
      stings. He was lacking cross-reactivity to honeybee venom, therefore we initiated
      immunotherapy with bumblebee venom extract. Two months after reaching the
      maintenance dose of 80 microg, the efficacy of the treatment was demonstrated by
      sting challenge.

PMID- 16433217
TI  - The great divide: more thoughts on an old problem.

PMID- 16433216
TI  - Latex-vegetable syndrome due to custard apple and aubergine: new variations of
      the hevein symphony.
AB  - An increasing number of vegetables with crossreactions to latex are being
      described in patients with latex-vegetable syndrome. We present two of these
      vegetables, custard apple linked in two previous cases with latex sensitisation,
      and aubergine, that had not been described up to now in patients with latex
      sensitisation. The diagnosis of both cases was based on the clinical history,
      positive skin prick test (SPT) and specific IgE to the offending vegetables, as
      well as to positive SPT and specific IgE levels to latex and the major fruits
      involved in the latex-fruit syndrome (avocado, banana, and chestnut). Further,
      crude extracts from latex, custard apple and aubergine, as well as the purified
      allergens Hev b 6.02 and Prs a 1 were used in in vitro and in vivo assays: IgE
      immunodetection, histamine release (HRT) and basophil activation (BAT) tests and
      skin prick tests. In case 1, both purified Hev b 6.02 and Prs a 1 induced
      positive responses in skin prick tests, high levels of basophil activation and
      histamine release. Specific IgE immunodetection uncovered a reactive band of 45
      kd in the crude custard apple extract, which was also recognized by anti
      chitinase monospecific antibodies. The serum from patient 1 also detected Prs a 1
      in immunodetection. Hev b 6.02 produced positive skin responses and showed high
      biological activity in HRT and BAT in the case of patient 2. However, Prs a 1 was
      reactive neither in SPT nor in IgE immunodetection. In fact, no band was detected
      using the serum of patient 2 in avocado or aubergine extracts. By contrast, Prs a
      1 reached high values of basophil activation and over 10% of histamine release in
      case 2.

PMID- 16433218
TI  - Vaccines, thimerosal, and neurodevelopmental outcomes.

PMID- 16433219
TI  - Noncardiac chest pain: a rational approach to a common complaint.

PMID- 16433220
TI  - Nonsurgical management of osteoarthritis of the knee.

PMID- 16433221
TI  - Are older patients satisfied with physician assistants and nurse practitioners?
AB  - OBJECTIVE: To determine how satisfied older American consumers are with physician
      assistant (PA) and nurse practitioner (NP) care. DESIGN: Cross-sectional national
      survey. SETTING: Noninstitutional, representative random sample of people aged 65
      years and older. PARTICIPANTS: Medicare recipients from the 2000 and 2001
      Medicare Satisfaction Survey, Consumer Assessment of Health Plans Survey section
      on Fee-for-Service, who identified a primary care provider. MEASUREMENTS: Patient
      sociodemographic characteristics, health care experience, and satisfaction data
      were compared in which a generalist physician, PA, or NP was identified as the
      personal provider. RESULTS: 146,880 completed returns from 321,407 randomly
      sampled Medicare beneficiaries nationwide (45.7% of the total surveyed) were
      analyzed with regard to satisfaction with their personal providers. Of this
      number, 3,770 identified a PA or an NP as their personal provider. For questions
      on satisfaction with their personal care clinician, results were similar for all
      three kinds of providers. A significantly higher proportion of the patients who
      reported NPs as their primary care providers were Medicaid recipients than were
      those patients who reported receiving care from PAs or physicians. Conversely, a
      significantly higher proportion of patients who were supplemental insurance
      recipients reported physicians as their primary care providers than were those
      who reported receiving care from PAs or NPs. CONCLUSION: Findings suggest that
      patients are generally satisfied with their medical care and do not distinguish
      preferences based on types of providers. PAs, NPs, and physicians in primary care
      seemed to be viewed similarly regardless of patient characteristics. PAs and NPs
      may be a workforce that could be expanded to care for the rising needs of the
      elderly.

PMID- 16433222
TI  - A percutaneous pinning misadventure.

PMID- 16433223
TI  - A 43-year-old woman with curious freckling of the lips.

PMID- 16433225
TI  - Patient information. Which diet is best--low-fat or low-carb?

PMID- 16433224
TI  - Which diet is better--low-fat or low-carb?

PMID- 16433226
TI  - Case of the Month. Chondrosarcoma.

PMID- 16433227
TI  - [Plants as a source of natural harmful substances].
AB  - In this review the several data concerning phytotoxins as natural harmful
      substances of plants and phycotoxins--toxicants of algae were described. For
      example plants are source of pyrrolizidine alkaloids, glycoalkaloids,
      glucosinolates as well as glycosides, saponine and psolarens. Possible adverse
      effects of phytoestrogens as endocrine disruptors versus beneficial influence
      these substances on human organism were mentioned. About lectins as possible
      factors of some diseases was reported, as well as some proteins as allergens of
      soy and peanuts was mentioned. Accumulated by shellfish and fish the most
      important phycotoxins such as saxitoxin, okadaic acid, brevetoxins and
      ciguatoxins were described. Phycotoxins produced several poisoning symptoms.
      Microcystins and nodularin--cyanobacterial phycotoxins of freshwater, was
      mentioned. In conclusion, the need of limitation of permissible levels of some
      plant toxicants, development of analytical methods as well as knowledge of
      influence of some technological processes on toxic plant substances was
      highlighted. The importance of balanced diet as a tool of defense against plant
      toxicants was concluded.

PMID- 16433228
TI  - [The heavy metals, nitrates and nitrites content in the selected vegetables from
      Lublin area].
AB  - The content of heavy metals (the lead, the cadmium) and nitrates and nitrites
      have been analyzed in the selected vegetables (lettuce, radish, spinach, chives,
      sorrel) obtained from the following allotments; the Lublin centre, the city
      surrounding and also from the marketplace and the supermarket. The tested
      vegetables did not exceed the acceptable lead and cadmium content norm. Most
      vegetables from the marketplace had a higher content of the analyzed heavy metals
      than the vegetables from the unpolluted areas (the allotments Lublin surrounding,
      the supermarket). The acceptable norm for nitrates was exceeded only in the
      radish and the chives which came from the allotments in the Lublin centre and
      also in the supermarket chives. The mean nitrites content in the test vegetables
      were not significant and were not harmful to people's health.

PMID- 16433229
TI  - [Calcium and phosphorous content in daily rations of adolescents from Biala
      Podlaska District].
AB  - The aim of the study was to assess the Ca and P intake and Ca:P ratio in daily
      rations of boys and girls aged 10-15 years. Calcium intake amounted to 51% and
      65% of safe intake level of RDA for 10-12 and 13-15 years old boys and 43% and
      44% for girls, respectively. Phosphorus intake exceeded the RDA and amounted to
      141-165% for boys and 122-133% for girls. It is suggested that persisting
      disproportions in Ca:P ratio (> or = 1:1,26) in daily rations may have
      disadvantageous effect on Ca metabolism, particularly in girls. A permanent
      nutritional education of children stressing the impact of proper nutrition on
      health, seem indispensable.

PMID- 16433230
TI  - [Evaluation of selected vitamins and minerals intake in pregnant women].
AB  - Evaluation of vitamins and minerals intake in pregnant women from Warsaw and
      Mazowsze Region was performed. The study was done in 2002-2003 with participation
      of 100 women, aged 10-40 years. The information about food intake was collected
      using 24-hour recall three times repeated. The study showed too low intake of
      vitamins of group B, especially folates (53% recommended value), vitamin B1
      (70%), vitamin B2 (82%). Intake of fat-soluble vitamins A and E was too high,
      above recommendation. Daily diet of pregnant women contained too low level of
      iron, copper, zinc and calcium, and too high phosphorus, and incorrect calcium
      and phosphorus ratio (0.22).

PMID- 16433231
TI  - [Quantitative and qualitative evaluation of group nourishment in 16-18 aged
      youths in a summer sports camp].
AB  - The purpose of this work was an attempt to evaluate the way of group nourishment
      among the teenage youths on a summer sports camp with respect to quantity and
      quality of food. The distribution of BMI rate among 165 girls and 131 boys--the
      participants of the camp was also estimated. The research showed that the
      analyzed decade menus were typically correct considering the average energetic
      value, they contained the overstandard amounts of protein and phosphorus,
      insufficiency of calcium, iron, magnesium and group B and C vitamins as well. At
      qualitative evaluation the analyzed menus received 21 points according to
      Starzynska's scale (satisfactory grade).

PMID- 16433232
TI  - [The estimation of the frequency of the consumption of breakfasts among rural
      children].
AB  - The purpose of the study was the estimation of the frequency and regularity of
      the consumption of breakfasts among rural children, and the examining of
      relations between the economic and social situation of families of the
      investigated children and the frequency of the consumption of breakfasts. The
      investigation included 2,584 girls and boys aged 7-15 years. The first breakfast
      was not eaten on the day of the investigation by over 1/5 of the schoolchildren,
      while light lunch was not eaten by over 1/8 school children. Children who come
      from well-off families consumed meals more regularly than children from poorer
      families.

PMID- 16433233
TI  - [A study of the Thermomyces lanuginosus lipolytic activity on tributyrin].
AB  - The study was to compare the lipolytic activity of Thermomyces lanuginosus wild
      strains on the medium containing 1-% tributyrin. The strains were isolated from
      raw coffee beans, shelled hazelnuts, mushroom compost, biohumus, garden compost
      and leaf compost. The incubation was carried out at 55 degrees C for ten days.
      The lipolytic activity index was the hydrolysis zone diameter/colony diameter
      ratio. Daily growth rates and daily clearance zone increase were also analyzed.
      All strains tested hydrolyzed tributyrin. The highest lipolytic activity index
      values were found in the strains isolated from raw coffee beans. Relatively high
      lipolytic activity index values were also found in the strains isolated from
      shelled hazelnuts. The highest lipolytic activity indices were observed between
      the 3rd and 5th day of incubation. It was hypothesized that the products of the
      tributyrin hydrolysis considerably affected both fungal growth and lipolytic
      activity. The T. lanuginosus strains isolated from raw coffee beans and shelled
      hazelnuts have a great biotechnological potential.

PMID- 16433234
TI  - [Influence of microbiological quality of lactic acid cheese on water phase in
      conditions of hermetic packing].
AB  - Aim of research was to assess the influence of lactic acid cheese micro-flora on
      water phase fluctuation between surface of products and the packaging. Results of
      research showed that changes of water content could be expressed with the help of
      polynomial cubic equation. From linear correlation equations describing level of
      micro-flora in lactic acid cheese and water content it resulted micro-organisms
      had a significant influence on the water phase fluctuation. Values of determined
      coefficients of determination suggested that yeast, enterococci and staphylococci
      had a significant influence on water fluctuation between product and the
      packaging.

PMID- 16433235
TI  - [The estimation of the influence of deionized water on the basic electrolytes
      level in blood and urine of tested animals].
AB  - Deionized water orally dosed, ad libitum dosage were tested on rats for 90 days
      period. The purpose of the experiment was the estimation of changes in aqua
      electrolytic economy of tested animals. Statistically relevant reduction of
      sodium, potassium, magnesium level in blood serum as well as in urine. In blood
      serum there were observed also statistically increase of calcium concentration
      whereas in urine calcium concentration descended. The results prove that drinking
      deionized water can cause similar unfavorable influence on mineral economy in
      human system.

PMID- 16433236
TI  - [Chemical emission from water-based adhesives for flooring materials].
AB  - Emissions of 2-(2-butoxyethoxy) ethanol, 2-(2-butoxyethoxy) ethyl acetate, 2
      fenoxyethanol, 2-ethylhexanol, alpha, beta pinene and total volatile organic
      compounds (TVOC) from water-borne adhesives for flooring materials were measured
      by means of emission test chamber 28 days (at 23 degrees C, 45% relative
      humidity, 0,5 air exchange/hour). For one adhesive the emission of 2 compounds
      was observed even after 28 days. TVOC emissions for one adhesive was very low.
      Some of adhesives may release of compounds which toxicity data have not been
      evaluated.

PMID- 16433237
TI  - [Value and limitations of programmed ventricular stimulation].
AB  - The electrocardiogramme and methods of prolonged ECG recording are sufficient for
      diagnosing most cardiac arrhythmias. They also provide some prognostic
      information and allow evaluation and follow-up of treatment. However, in some
      situations, endocavitary electrophysiological investigations are required when
      the diagnosis is uncertain, that more prognostic information is required or
      interventional techniques (endocavitary ablation) are envisaged. The aim of this
      report is to summarise the value and limitations of programmed ventricular
      stimulation. Many of its indications have been abandoned in terms of rhythm
      stratification in the face of more robust parameters, in particular the left
      ventricular ejection fraction. However, it retains a potential utility in terms
      of prognosis in arrhythmogenic right ventricular dysplasia, the Brugada syndrome
      and operated Tetralogy of Fallot. In any event, it is important to remember that
      studies resulting in diagnostic or therapeutic recommendations were performed
      with strict protocols of stimulation in selected patients and that these
      recommendations can only be applied when the evaluation protocols are respected.
      The indications of programmed ventricular stimulation will increase in the
      therapeutic field with the development of new techniques of 3D mapping, new
      systems of catheter guiding which should extend the indications of endocavitary
      ablation.

PMID- 16433238
TI  - [Ventricular tachycardia due to branch to branch re-entry].
AB  - Ventricular tachycardia due to branch to branch re-entry constitutes a rare
      clinical entity. This circuit is remarkable by the fact that it is made up of the
      branches or hemi-branches of the bundle of His bifurcation. They occur under
      specific conditions, with a combination of left ventricular dilatation and
      atrioventricular or intraventricular conduction defects. They are also very often
      found in Steinert's disease. A positive diagnosis can sometimes be difficult and
      relies on a variety of factors. Recording of the His potential shows His activity
      preceding each ventriculogram, and variations in spontaneous cycles between 2
      ventriculograms preceded by variations between the 2 His potentials. Atrial
      capture without modification of the QRS is possible, but fusion excludes the
      diagnosis. Drug therapy is only slightly effective, and the best treatment is
      ablation of the right branch of the bundle of His, which stops the tachycardia
      definitively.

PMID- 16433239
TI  - [Primary anomalies of ventricular repolarisation].
AB  - The duration of repolarisation is the main determinant of the refractory period
      and therefore plays a major electrophysiological role. Ventricular repolarisation
      can be influenced or modified by very many extrinsic factors responsible for so
      called secondary changes or anomalies. On the contrary, primary anomalies of
      ventricular repolarisation correspond to intrinsic anomalies of ionic conduction
      which in turn affect repolarisation. Primary anomalies of ventricular
      repolarisation are the consequences of vascular disease, which is the origin of
      both electrocardiographic anomalies and rhythm disorders, and which can result in
      sudden death from ventricular fibrillation. Three clinical syndromes correspond
      with these definitions: long QT syndrome, short QT syndrome, and Brugada
      syndrome. Much of the experimental work seems to show that arrhythmogenic action
      results mostly from an increase in the heterogeneity of the refractory periods,
      whether this involves a prolonged, short or even normal repolarisation time. The
      various experimental models also give a better understanding of the
      repolarisation changes observed on the electrocardiogram. Knowledge of the
      mechanisms responsible for arrhythmias due to primary anomalies of ventricular
      repolarisation could provide a model for secondary anomalies.

PMID- 16433240
TI  - [Rhythm disorders and cardiac crypto-malformations].
AB  - Faced with a cardiac arrhythmia occuring in an apparently healthy heart, it is
      necessary to perform an anatomical investigation to detect any unsuspected
      anomalies. Congenital cardiopathy must certainly be excluded, as this is often
      responsible for rhythm disorders and/or cardiac conduction defects. Similarly,
      any acquired conditions, cardiomyopathy, or cardiac tumour must be sought.
      However, the possibility should always be considered of a minimal congenital
      malformation, which could be repsonsible for: any type of cardiac arrhythmia:
      rhythm disorder or conduction defect at the atrial, junctional or ventricular
      level, with a benign or serious prognosis. Unexpected therapeutic difficulties
      during radiofrequency ablation procedures or at implantation of pacemakers or
      defibrillators. Together with rhythm studies, the investigation of choice is high
      quality imaging, either the classic left or right angiography or the more modern
      cardiac CT or intracardiac mapping.

PMID- 16433241
TI  - [Mapping and ablation of malignant ventricular arrhythmias].
AB  - Endocavitary investigations showed that the ventricular extrasystoles originated
      in the common ventricular myocardium (pulmonary infundibulum) in only 9 cases
      whereas the majority arose from the Parkinje system either on the anterior wall
      of the right ventricle or in septal region of the left ventricle. The
      extrasystoles arising from the Parkinje system and pulmonary infundibulum
      differed in their duration and polymorphism (128 +/- 18 ms vs 145 +/- 13 ms, p =
      0.05; 3.3 +/- 2.7 morphologies vs 1.1 +/- 0.4, p < 0.001, respectively). During
      the extrasystoles, the local Pukinje potential preceded the ventricular
      activation by variable intervals, some of which were very long, up to 150 ms.
      Seven applications of radiofrequency were delivered on average per patient on the
      most distal part of the Purkinje system leading to ablation of the specific
      activation. The clinical results were spectacular: 88% of patients had no further
      episodes of ventricular fibrillation as demonstrated by analysis of the
      defibrillator with an average follow-up period of more than 34 months.

PMID- 16433242
TI  - [Sick sinus syndrome].
AB  - Sick sinus syndrome is an association of sinus node dysfunction with bradycardia,
      pauses, sino-atrial block, chronotropic insufficiency and atrial arrhythmias. The
      diagnosis is essentially clinical and electrocardiographic. Prolonged ECG
      recordings allow a better assessment of the severity of the condition whereas
      electrophysiological investigations only provide complementary information which
      is rarely decisive in the therapeutic indications. Cardiac pacing is the
      treatment of choice for symptomatic patients: significant improvement in symptoms
      may be expected but there is no significant change in survival. Single chamber
      atrial stimulation or dual chamber pacing is preferable to single chamber
      ventricular pacing, especially with regards to the incidence of atrial
      fibrillation and the impact on quality of life.

PMID- 16433243
TI  - [Arrhythmia and sport].
AB  - Sports arrhythmia has gained wide attention with the mediatization of the death
      of famous sports stars. Sport strongly modifies the structure of the heart with
      the development of left ventricular hypertrophy which may be difficult to
      differentiate from that due to doping. Intense training modifies also the resting
      electrocardiogram with appearance of signs of left ventricular hypertrophy
      whereas resting sinus bradycardia and atrioventricular conduction disturbances
      usually reverts upon exertion. Accordingly, arrhythmia may develop ranging from
      extrasystoles to atrial fibrillation and even sudden death. Recent data suggest
      that if benign arrhythmia may be the result of the sole intense training and are
      reversible, malignant ventricular arrhythmia and sudden death mostly occur in
      unknown structural heart disease. Hypertrophic cardiomyopathy is amongst the most
      frequent post mortem diagnosis in this situation. Doping is now present in many
      sports and further threatens the athlete in the safe practice of sport.

PMID- 16433244
TI  - [Evaluation and surveillance of patients with an implantable defibrillator].
AB  - The implantable cardioverter-defibrillator became in some years the reference
      treatment of ventricular arrhythmias in association with heart disease. Recently,
      this technique showed its efficiency in primary prevention for patients at high
      risk of sudden death. The follow-up of patients with automatic defibrillator
      requires a detailed knowledge of both electrophysiology and stimulation. This
      training is based on a practical and theoretical formation. In France, a specific
      diploma validation is necessary and centres organisation is required. The purpose
      of this general review is to supply a set of updated data necessary for the
      coverage and the follow-up of patients with an implantable cardioverter
      defibrillator.

PMID- 16433245
TI  - Alternatives for measuring endogenous adrenocortical activity in asthmatics
      treated with inhaled corticosteroids.
AB  - We compared a 12-hour, hourly integrated plasma cortisol profile in asthmatics
      treated with a corticosteroids with a variety of modified methods based on less
      frequent blood sampling. Excellent agreement with the reference was observed for
      sampling at 10 p.m. and 8 a.m. (correlation coefficient of 0.97; 95 % confidence
      interval 0.97, 0.98); at 9 p.m. and 7 a.m. (r = 0. 95; 0. 94, 0.96); at 11 p.m.
      and 7 a.m. (r = 0.94; 0.93, 0.95); every 2 hours (r = 0. 96; 0.96, 0.97); and
      every 3 hours (r = 0. 91, 0.91, 0.93). The two-sample alternatives (10 p.m/8 a.m.
      and 9 p.m/7 a.m.) are accurate, as well as more convenient, economical, and
      practical.

PMID- 16433246
TI  - Muscarinic M1 and M3 receptor binding alterations in pancreas during pancreatic
      regeneration of young rats.
AB  - The importance of muscarinic receptors in proliferation of different cell types
      and in insulin secretion from pancreatic beta cells has been extensively studied.
      However, the role of pancreatic muscarinic receptors during pancreatic
      regeneration has not yet been studied. For the first time, the functional status
      of the muscarinic M1 and M3 receptors in regeneration of the pancreas is
      investigated here. It is observed that the number and affinity of high-affinity
      muscarinic M3 receptors increased at the time of regeneration. The low-affinity
      M3 receptors also showed a similar trend. In the case of muscarinic M1 receptors,
      the receptor number increased with a decrease in affinity. We also observed an
      increase in the circulating insulin levels at the time of active regeneration.
      The in vitro studies confirmed that muscarinic receptors are stimulatory to
      insulin secretion. Our results suggest that the increased muscarinic M1 and M3
      receptor subtypes stimulate insulin secretion and islet cell proliferation during
      the regeneration of pancreas.

PMID- 16433247
TI  - Physiologic testosterone therapy has no effect on serum levels of tumour necrosis
      factor-alpha in men with chronic heart failure.
AB  - Physiological testosterone therapy increases exercise capacity and reduces
      symptom scores in men with chronic heart failure (CHF). Tumour necrosis factor
      alpha (TNF-alpha) exerts a significant pathologic activity in CHF, and
      physiologic testosterone replacement therapy is associated with reduced serum
      levels of TNF-alpha in hypogonadal men with concomitant coronary artery disease.
      It is unknown whether testosterone exerts a similar immunomodulatory action in
      men with CHF. Testosterone therapy administered in three placebo-controlled
      studies, for either 6 hours (two 30-mg buccal tablets, n=12) or 3 months
      (fortnightly 100 mg intra muscular injection, n=20; or daily 5 mg transdermally,
      n=62). The effects of testosterone were also assessed on lipopolysaccharide (LPS)
      induced TNF- production in whole blood obtained from 27 men with CHF. Incubation
      with testosterone (10 nM, 1 M, and 100 M) resulted in a reduction in LPS-induced
      TNF- production from 12.6 +/- 1.3 to 11.2 +/- 1.1 (P = 0.053), 10.3 +/- 1.1 (P =
      0.0046), and 9.2 +/- 1.1 (P = 0.000066) ng/ml, respectively. However in men with
      CHF, serum levels of TNF- were similar before and after treatment with
      testosterone or placebo, irrespective of the length of study or route of
      administration. The clinically beneficial actions of testosterone in men with CHF
      are unlikely to be mediated by reducing TNF-alpha.

PMID- 16433248
TI  - Lack of association between androgen receptor polymorphisms and bone mineral
      density or physical function in older men.
AB  - Individuals whose androgen receptors have short polyglutamine tracts (resulting
      from CAG repeats) may have greater receptor signaling activity of the androgen
      receptor. We evaluated the association between bone mineral density (BMD) and CAG
      repeats in 91 older men with normal (control) and low femoral neck (EN) BMD (OP)
      or a history of femoral fracture (FX). Bioavailable testosterone (BioT) and
      physical performance, including composite score (EPESE) and physical activity
      (PASE), were also measured. Comparing FX, OP, and control subjects, we observed
      BMD Tscores of -2.16 +/- 1.08, -2.26 +/- 0.74, and -0.20 +/- 0.40 (p < 0.001);
      CAG repeat lengths of 21.9 +/- 2.7, 22.5 +/- 2.4, and 22.3 +/- 2.9 (p = 0.63);
      BioT levels of 2.29 +/- 1.25, 2.19 +/- 1.11, and 3.99 +/- 1.25 nmol/L (p <
      0.001); EPESE scores of 8.0 +/- 3.0, 9.7 +/- 2.0, and 11.3 +/- 0.9 (p < 0.001);
      and PASE scores of 91 +/- 66, 122 +/- 66, and 200 +/- 55 (p < 0.001),
      respectively. There were no significant correlations between CAG repeats and BioT
      or physical performance. Men with osteoporosis or fracture had lower BioT,
      physical performance, and physical activity than controls. This study found no
      association between CA G repeats and FN BMD in older men with normal or low BMD
      or FX.

PMID- 16433249
TI  - Peripheral patterns of growth hormone, luteinizing hormone, and progesterone
      before, at, and after puberty in buffalo heifer.
AB  - Buffalo, the premier dairy animal in India, suffers from slow growth rate,
      delayed puberty, and silent heat. It is not known whether the delay in puberty in
      such animals is due to the delay in expression of hypothalamus-pituitary-gonadal
      functions. To determine the changes in growth hormone (GH), luteinizing hormone
      (LH), and progesterone before, at, and after puberty of Murrah buffalo heifers,
      six Murrah buffalo heifers (21.92 +/- 1.09 months of age, 269.67 +/- 7.97 kg body
      weight) were assigned to well-ventilated individual pens and fed a roughage
      concentrate diet to provide weight gain of 0.4 kg/day. Blood samples were
      collected at 3-day intervals during a period of 12 months, and plasma harvested
      from blood samples was assayed for progesterone, LH, and GH. The day that plasma
      progesterone was greater than 1 ng/mL for three consecutive sampling days was
      defined as the day of puberty. Heifers attained puberty at an average age of
      31.53 +/- 0.88 months with a body weight of 380.67 +/- 6.42 kg. Progesterone
      levels were very low (0.20 to 0.30 ng/mL) during the pre-pubertal period. There
      were two distinct elevations before the day of puberty onset. Plasma LH and GH
      concentrations increased (P < 0.05) during the months preceding puberty and were
      highest during the month before puberty. GH and LH were positively correlated (P
      < 0.05) prior to (r = +0.59) as well as after puberty (r = +0.42). A positive
      correlation (P < 0.05)between LH and body weight during the pre-pubertal period
      (r = +0.61) and thereafter, negative correlation (P < 0.05) during post-pubertal
      period (r = -0.64) was noted. GH and body weight showed positive correlation both
      before puberty (r = +0.92, P < 0.01) and after puberty (r = +0.32, P < 0.05).
      Results suggest that both GH and LH are equally important and vital cues in
      inducing onset of ovarian functions in buffalo heifers.

PMID- 16433250
TI  - A novel double mutation in the luteinizing hormone receptor in a kindred with
      familial Leydig cell hypoplasia and male pseudohermaphroditism.
AB  - We report a novel mutant of the luteinizing hormone receptor (LHR) in a case of
      familial Leydig cell hypoplasia and pseudohermaphrotidism. The proband was
      homozygous for two missense mutations, T1121C and C1175T, causing substitutions
      I374T and T3921. The molecular effects of the mutations were investigated by
      heterologous expression of the WT LHR, the double mutant LHR, or receptors with
      either the I374T or the T392I mutation, and measuring hormone binding and cAMP
      signaling. All mutant LHRs exhibited severe defects, including loss of ligand
      binding and cAMP production. Immunoblots showed little difference in protein
      levels between the WT and mutant receptors.

PMID- 16433251
TI  - A comparison between the effects of low (1 microg) and standard dose (250 microg)
      acth stimulation tests on adrenal cortex functions with leprosy patients.
AB  - Leprosy is a chronic granulomatous disease that either remains localized or
      widespread depending on the immunological status of the affected patient. It can
      lead to clinical or subclinical adrenal failure by influencing adrenal
      steroidogenesis. In the present study, 26 patients (21 males and 5 females) who
      were diagnosed with lepromatous leprosy and 15 healthy individuals who were
      compatible with the patients in terms of age and sex were subjected to an
      adrenocorticotrophic hormone (ACTH) stimulation test. The leprosy and control
      groups were subjected to 1microg low dose (LDT) and 250 microg intravenous
      standard dose (SDT) ACTH stimulation tests after 12-hour nocturnal fasting with
      an interval of three days. Cortisol responses in 0, 30, and 60 minutes were
      examined. There was no difference between leprosy and control groups in terms of
      mean baseline cortisol values. Mean value of the peak cortisol response to both
      LDT and SDT was found to be significantly lower in the leprosy group than in the
      control group (p < 0.001 and p < 0.01, respectively). Peak cortisol response to
      LDT in the leprosy group was found below 20 microg/dL in 9 patients (34.6%). As
      for the peak cortisol response to SDT, it was lower than 20 microg/dL, in 5
      patients (19.23%). It was found that LDT response was abnormally low in 4
      patients (15.38%) who responded normally to SDT. It was observed that there could
      be a decrease in adrenocortical reserve capacity although baseline adrenocortical
      functions were normal in patients with leprosy. It was seen that LDT was more
      sensitive than SDT in identifying this decrease.

PMID- 16433253
TI  - Study of subclinical cerebral edema in diabetic ketoacidosis by magnetic
      resonance imaging T2 relaxometry and apparent diffusion coefficient maps.
AB  - Cerebral edema is the most significant complication in children with diabetic
      ketoacidosis (DKA). Our goal was to study whether subclinical cerebral edema was
      preferentially vasogenic or cytotoxic. Magnetic resonance imaging (MRI)-
      diffusion-weighted imaging (DWI) and T2 relaxometry (T2R)--were obtained in
      pediatric patients presenting with severe diabetic ketoacidosis (DKA) 6-12 hours
      after initial DKA treatment and stabilization and 96 hours after correction of
      DKA. T2 relaxometry was significantly increased during treatment in both white
      and gray matter, in comparison to the absolute T2R values 96 hours after
      correction of DKA (p = .034). Classic intracellular cytotoxic edema could not be
      detected, based on the lack of a statistically significant decrease in ADC
      values. ADC values were instead elevated, implying a large component of cell
      membrane water diffusion, correlating with the elevated white and gray matter T2R
      We discuss the findings in relation to cerebral blood volume, cerebral
      vasoregulatory dysfunction, and cerebral hyperemia.

PMID- 16433252
TI  - The inverse relationship between thoracic aortic intima media thickness and
      testosterone level.
AB  - BACKGROUND: It is known that testosterone prevents coronary artery disease, and
      lower testosterone level is a risk factor for ischemic heart disease in men.
      However, there is no report showing the relationship between testosterone level
      and severity of thoracic aortic atherosclerosis. AIM: To investigate whether a
      relationship exists between atherosclerotic thoracic aortic intima media
      thickness (TAIT) and testosterone level. METHOD: Forty-two male patients (mean
      age 56 +/- 12 years) without a history of atherosclerotic cardiovascular disease
      referred for transesophageal echocardiography (TEE) were included. Intima media
      thickness of aorta was evaluated in each patient by using TEE. Testosterone
      levels were measured using a commercial kit. Blood chemistry parameters were
      measured by automated analyzers. The data obtained was evaluated by using
      correlation analyses and linear regression analysis tests. RESULTS: Mean
      testosterone values were 507 +/- 209 ng/dl. Testosterone levels showed a negative
      significant correlation with TAIT (r = -765, p < 0.001). In addition,
      testosterone levels showed positive correlations with albumin (r = 0.690, p =
      0.019) and negative correlations with uric acid (r = -0.630, p < 0.001), HsCRP (r
      = -0.449, p = 0.003), fibrinogen (r = -0.508, p = 0.001), and white blood cells
      (r = -0.433, p = 0.005). On the other hand, multiple linear regression analysis
      showed that TAIT was independently associated with testosterone and uric acid
      (beta = -0.610, p = 0.002 versus beta = 0.409, p = 0.026 respectively).
      CONCLUSION: This study indicates that there is an independent relationship
      between testosterone and TAIT.

PMID- 16433254
TI  - The expression of estrogen, prolactin, and progesterone receptors in mammary
      gland and liver of female rats during pregnancy and early postpartum: regulation
      by thyroid hormones.
AB  - The aim of this study was to examine, using semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) the changes in mRNA expression
      of the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, prolactin
      receptor long and short form, and progesterone (Pg) receptor (PgR), in liver and
      mammary gland during gestation, early lactation, and weaning in both hyperthyroid
      (HT) and normal rats. Pregnancy increased long prolactin receptors (PRL-R(L)) and
      ERalpha mRNAs in liver and PRL-R(I) in mammary gland. Lactation decreased PRL
      R(L) in liver and ERbeta and PgR in mammary gland. HT decreased PRL-R(L), at the
      end of pregnancy (G21), ERalpha (in G21 and L1) in liver and PRL-R(L) in L1 as
      well as short prolactin receptors (PRL-R(S)) (G7, L1) and ERbeta (G7, G14, L4) in
      mammary gland. In conclusion, our data indicated that (1) PRL-R1 and ERalpha
      expression levels are differentially regulated in the liver, and PgR and ERbeta
      in mammary gland during pregnancy and lactation (2) ERbeta is variably expressed
      depending on the state of thyroid hormones, however the ERalpha gene expression
      remained constant in mammary gland. (3) PRL-R1 mRNA expression is highly induced
      in the mammary gland during late pregnancy and abruptly declines on the first day
      of lactation for the HT rats.

PMID- 16433255
TI  - Cortisol circadian rhythm and 24-hour Holter arterial pressure in OSAS patients.
AB  - Obstructive sleep apnea syndrome (OSAS) is a syndrome in which the principal
      symptom is apnea during sleep. Hypoxia in OSAS is a stress condition, which when
      prolonged in time, could alter hypothalamo-hypophysial-suprarenal control and the
      cortisol cicadian rhythm. We studied 28 patients with OSAS (30-60 years old), 20
      female and 8 male. We calculated the OSAS class according to the Simmons
      classification. Twenty of the 28 patients maintained unmodified cortisol
      circadian rhythms, while 8 had cortisol levels more elevated in late and
      nocturnal hours. Holter monitoring showed arterial hypertension in 8 of the 28
      patients (the same patients with cortisol circadian rhythm alteration). Our data
      seem to indicate that when the OSAS patients lack cortisol circadian rhythm they
      are having arterial hypertension.

PMID- 16433256
TI  - Leptin does not induce hypertrophy, cell cycle alterations, or production of MCP
      1 in cultured rat and mouse cardiomyocytes.
AB  - BACKGROUND: Leptin has been proposed as an important mediator in cardiovascular
      pathophysiology. Patients with congestive heart failure (CHF) present high plasma
      leptin levels. CHF is generally preceded by myocardial remodeling involving
      hypertrophy, necrosis, and apoptosis. AIM: To investigate whether leptin causes
      hypertrophy or cell cycle alterations, or induces MCP-1 synthesis in
      cardiomyocytes. METHODS: Primary cultures of neonatal rat cardiomyocytes (PC) and
      murine cell line HL-1 were used. RT-PCR was used to identify Ob-Rb gene
      expression. Metabolic activity and proliferation of cardiomyocytes was studied
      using MTT and BrdU uptake, while apoptosis was assayed with Hoechst dye vital
      staining and flow cytometry. Measurement of the cell surface area was used to
      determine hypertrophy. MCP-1 levels were measured by ELISA. RESULTS: RT-PCR
      showed Ob-Rb mRNA expression in HL-1 cells. Exposure to leptin induced no changes
      in metabolic activity, proliferation, and apoptotic rates, and did not alter cell
      cycle in cardiomyocytes. Leptin did not increase cell size of cardiomyocytes, and
      MCP-1 synthesis was not detected in PC and HL-1 cells treated with leptin.
      CONCLUSION: This work shows that leptin does not induce changes in viability,
      proliferation, size or apoptosis of rat neonatal and HL-1 cardiomyocytes, and it
      does not induce MCP-1 secretion in these cells.

PMID- 16433257
TI  - Leptin stimulates LH secretion in peripubertal male rats through NMDA receptors.
AB  - Leptin, a peptide hormone secreted by adipocytes that has been proposed as a
      metabolic signal in the reproductive system, appears to be linked to the
      different neuroendocrine processes involved in the onset of puberty. We studied
      the ontogenic effect of administration of leptin (30 mg/kg i.p.) on serum LH
      levels during different stages of sexual development (7, 30, and 45 days of age)
      in male rats and on the hypothalamic content of glutamate (GLU) and gamma
      aminobutyric acid (GABA) in 30-day-old rats. Leptin induced a significant
      increase (p < 0.01) in LH levels in 30 days old rats. This hormone stimulatory
      effect was accompanied by a significant enhancement (p < 0.01) of the
      hypothalamic content of glutamate, the hypothalamic excitatory aminoacid involved
      in N-methyl-D-aspartate (NMDA) neurotransmission. No changes in the LH plasma
      levels were observed in 7- and 45-day-old male rats treated with leptin. MK 801
      (0.1 and 0.3 mg/kg i.p.), an antagonist of NMDA receptors of excitatory amino
      acid system (EAAs), antagonized the stimulatory effect of leptin on LH secretion
      and on the hypothalamic content of GLU. These results demonstrate that leptin
      stimulates the reproductive axis in male rats during a determined period of
      sexual maturation and that NMDA receptors are involved in thefacilitatory action
      of leptin on the gonadal axis of male rats during sexual maturation.

PMID- 16433259
TI  - [Expression of fibroblast growth factor and c-fos proto-oncogene in burned wound
      in rats and their influence on wound healing].

PMID- 16433258
TI  - Low triiodothyronine (T3) or reverse triiodothyronine (rT3) syndrome modifies
      gene expression in rats with congestive heart failure.
AB  - Heart failure (HF) is frequently associated with euthyroid "sick" syndrome (low
      T3 and elevated rT3). We investigated if altered thyroid hormone in HF could
      affect expression of the TH receptor (TRalpha1), and alpha and beta myosin heavy
      chains (alpha-MHC, beta-MHC). HF was provoked in rats by aortic stenosis. We
      showed that rT3 generated from liver and kidney deiodination significantly
      increased and T3 decreased in HF; there was significantly higher TRalpha1
      expression, no alpha-MHC expression, but beta-MHC expression. Changes in TRalpha
      could be compensating for low T3 from HF.

PMID- 16433260
TI  - [Medicine and self-help: development of a partnership].

PMID- 16433261
TI  - [An overview of self-help structures in Germany].
AB  - Self-help groups, self-help organizations, and clearing-houses have now become
      recognized elements of the health care system. Organized self-help, which has a
      long tradition in Germany, gained significant momentum during the 1980s and
      1990s. Several factors still contribute to the development of self-help groups:
      the increased number of chronic health conditions, the improved treatment
      programs, increasing life expectancies, changes in primary social networks
      (family, relations, and neighborhood), and increased public recognition of the
      value of self-help. There are approximately 280 self-help clearinghouses and a
      large number of topic-specif ic self-help organizations in Germany; these form
      the mainstay of effective self-help support for those who are affected or engaged
      and are interested in self-help. It is estimated that approximately 3 million
      individuals are engaged in 70,000 to 100,000 self-help groups, covering virtual
      ly every topic relating to medical, psychological, and social issues.
      Representative surveys have revealed that three quarters of the population would
      turn to a self-help group in case of illness, although experience shows that only
      a minority actually does. In addition, there is still a significant lack of
      information about self-help and its organizational structure.

PMID- 16433262
TI  - [Need-oriented support offers of self-help groups for handicapped or chronically
      ill people].
AB  - During the last decades, self-help groups and self-help organizations have become
      an important part of the health system. Their success is explained mainly by the
      fact that their support offers are fully oriented to the needs of people with
      handicaps or chronic diseases. The present paper describes the support
      requirements of people with handicaps or chronic diseases, the type of need
      oriented offers they request, and the types of self-help groups available for the
      corresponding support, including the identification of factors contributing to
      their performance and the difficulties inherent to their organization.

PMID- 16433264
TI  - [Self-care--the contribution of nursing sciences to health care].
AB  - The future development of the German health care system needs to recognize
      patient views of medical treatment in order to foster their health care
      responsibility. In nursing sciences, practice and clinical research are based on
      the concepts of self-help and self-care. The principle of Self-Care Deficit
      Nursing Theory (S-CDNT), developed by the American nursing scientist D.E. Orem,
      defines self-care as a trainable and deliberate practice. The theory describes,
      among other factors, general and situation-specific needs of self-care and
      dependence care, forms of self-care com petence, and self-care deficit. Clinical
      studies have focused on self-care activities and deficits of particular patient
      groups, testing the effectiveness of care interventions. In view of the changes
      in the German health system (e.g., diagnosis-related groups, reduction of
      hospitalization periods), the S-CDNT is relevant not only for the treatment of
      individual patients, but also for the management of care provision. The fostering
      of self-care and dependence-care competence is an important tool to increase the
      autonomy of affected patients and their families, as well as to reduce the costs
      of health care.

PMID- 16433263
TI  - [Advantages of cooperation with self-help organisations for out-patient
      physicians].
AB  - AIM OF THE STUDY: Self-help groups and organisations are important contributors
      to the provision of rheumatological care. No systematic studies exist thus far on
      the cooperation between professional care providers and the German Rheumatism
      League, the most significant patient organisation for rheumatoid patients.
      METHODS: To gain information about the extent of the co-operation between
      rheumatologists and the German Rheumatism League and to estimate the benefits of
      the co-operation, a survey was conducted among German rheumatologists in the out
      patient sector (n = 787). RESULTS: The response rate was 40.7%. As many as 98.7%
      of the rheumatologists were informed about self-help initiatives, with 78.1%
      receiving this information from their own patients. Regular or frequent co
      operation with self-help initiatives was reported by 46%. Among the physicians
      with experience in co-operation, 84.1% wished more contact with self-help
      initiatives, compared with only 61.9% of non-experienced physicians. The benefit
      of the activities of the Rheumatism League was highly appreciated: the long-term
      training of functional capacity was evaluated as helpful by 73.4%; the training
      for coping with pain by 62.2%; the occupational therapy groups by 60.6%; the
      patient-education groups by 61.6%; and the self-help groups by 56.3%. The benefit
      of co-operation was appreciated more by rheumatologists experienced in co
      operation than by rheumatologist without specific experience: on a rating scale
      from 1 (little benefit) to 6 (high benefit) the former group scored an average of
      3.7, the latter an average of 2.7. DISCUSSION AND CONCLUSIONS: In spite of the
      relatively low response rate (40.7%), the results cover a relevant part of
      rheumatologists in the out-patient sector. The more experience physicians have
      with co-operation, the higher they estimate the benefits of co-operation with the
      Rheumatism League. This underlines the necessity of technical information about
      self-help initiatives and the promotion of contacts and co-operation in the
      rheumatological out-patient sector.

PMID- 16433265
TI  - [Methodologic article concerning Frequently Asked Questions: should English
      articles be translated?].

PMID- 16433266
TI  - [Randomization and comparison of final quality in clinical studies].

PMID- 16433268
TI  - [Feelings of "Portuguese-Spanish" nurses].

PMID- 16433267
TI  - [Cycloid psychosis].

PMID- 16433269
TI  - [Indwelling catheters: their most common mechanical and pathogenic problems].

PMID- 16433270
TI  - [Machado Joseph disease].

PMID- 16433271
TI  - [Should we include family members in the care of hospitalized patients?].

PMID- 16433273
TI  - [Narrative research: a feasible method in clinical nursing].

PMID- 16433274
TI  - [Newborn infants in phototherapy].

PMID- 16433275
TI  - [Breast self-examination].

PMID- 16433276
TI  - A report from the 77th annual convention and exibit of the American Health
      Information Management Association (AHIMA) held in San Diego, California 15th -
      20th October 2005.

PMID- 16433277
TI  - Sponsored hospital literature.

PMID- 16433278
TI  - Geneticization of deviant behavior and consequences for stigma: the case of
      mental illness.
AB  - One likely consequence of the genetics revolution is an increased tendency to
      understand human behavior in genetic terms. How might this "geneticization"
      affect stigma? Attribution theory predicts a reduction in stigma via reduced
      blame, anger, and punishment and increased sympathy and help. According to
      "genetic essentialist" thinking, genes are the basis of human identity and
      strongly deterministic of behavior. If such ideas are commonly accepted,
      geneticization should exacerbate stigma by increasing perceptions of
      differentness, persistence, seriousness, and transmissibility, which in turn
      should increase social distance and reproductive restrictiveness. I test these
      predictions using the case of mental illness and a vignette experiment embedded
      in a nationally representative survey. There was little support for attribution
      theory predictions. Consistent with genetic essentialism, genetic attributions
      increased the perceived seriousness and persistence of the mental illness and the
      belief that siblings and children would develop the same problem. Genetic
      attribution did not affect reproductive restrictiveness or social distance from
      the ill person but did increase social distance from the person's sibling,
      particularly regarding intimate forms of contact involving dating, marriage, and
      having children.

PMID- 16433279
TI  - The self and mental health: self-salience and the emergence of internalizing and
      externalizing problems.
AB  - How do schemas about self-salience--the importance of the self versus the
      collective in social relations--affect mental health? We propose that self
      salience shapes the likelihood of experiencing internalizing or externalizing
      problems. Schemas that privilege others over the self increase the risk of
      internalizing symptoms, including depressive symptoms and anxiety, whereas those
      that privilege the self over others predispose individuals to externalizing
      behaviors of antisocial behavior and substance abuse. Furthermore, we propose
      that these schemas contribute to the gender differences that exist in these
      problems. We test these predictions with data from adolescents, the stage at
      which these problems and the gender differences in them arise. Results show that
      self-salience underlies both internalizing and externalizing problems. In
      addition, schemas about self-salience help explain the gender differences found
      in mental health problems.

PMID- 16433280
TI  - Clarifying the relationship between parenthood and depression.
AB  - Unlike other major adult social roles in the United States, parenthood does not
      appear to confer a mental health advantage for individuals. However, while
      research has examined parental status differences in emotional well-being,
      relatively little is known about variations in emotional distress among parents.
      In this article, we clarify the relationship between parenthood and current
      symptoms of depression using data from the National Survey of Families and
      Households. The analyses provide support for our first hypothesis: Parenthood is
      not associated with enhanced mental health since there is no type of parent who
      reports less depression than nonparents. We also find support for our second
      hypothesis: Certain types of parenthood are associated with more depression than
      others. Additionally, although we find marital status differences in symptoms
      among parents, there are no gender differences in the association between
      parenthood and depression. We discuss the implications of our findings for
      ongoing theoretical debates about the advantages of social role involvement for
      mental health as well as the meaning of contemporary parenthood in the United
      States.

PMID- 16433281
TI  - Household income histories and child mental health trajectories.
AB  - Although it is widely accepted that low household income is associated with worse
      child mental health, less is known about whether income histories, often
      differentiated into stable and dynamic components, also matter. Using
      longitudinal data from the Child Supplement of the National Longitudinal Study of
      Youth, comprising the repeated measures of children ages 4 to 14 from 1986 to
      1998 inclusive, I estimate generalized linear mixed models to evaluate the
      influence of household income histories on child depression and antisocial
      behavior over time. Results indicate that, at initial interview, low household
      income is associated with higher levels of depression and antisocial behavior;
      subsequent improvements in household income reduce child mental health problems.
      Further, the effect of initial household income on the rate of change in child
      depression attenuates as children grow older, whereas for antisocial behavior the
      effect of initial household income becomes stronger over time. These findings
      highlight the importance of understanding the ways in which children are
      influenced by their families' income histories.

PMID- 16433282
TI  - A 3-D model of health decline: disease, disability, and depression among Black
      and White older adults.
AB  - Much of the research on health decline in older adulthood has specified a single
      causal direction between two health domains, often measured at the same time
      point, making it difficult to disentangle the mechanisms of health decline over
      time. Using three waves of data over seven years from older residents of North
      Carolina, a 3-D model is used to examine the temporal ordering of general health
      decline and the pathways of influence across three health domains (disease,
      disability, and depression). In addition, we test whether the 3-D model of health
      decline is similar for Black and White older adults. Results indicate that both
      prevalent and incident disease lead to increases in depression and that prevalent
      disease leads to greater disability three years later. Depression, in turn, leads
      to disease, identifying a cycle of health decline that is, for the most part,
      similar for Black and White older adults. The effect of widowhood is more
      deleterious to the health of Black older adults than for their White
      counterparts.

PMID- 16433283
TI  - Community reaction to persons with HIV/AIDS and their parents: an analysis of
      recent evidence from Thailand.
AB  - We systematically examine community reaction to persons living with HIV/AIDS
      (PHAs) and their older parents in Thailand. We focus on parents as well as PHAs
      because parents are major providers of care for their ill adult children. Our
      analyses are based on several sources of recently collected survey and
      qualitative data from a wide range of perspectives. We find important variations
      in community reaction to PHAs and their families, but overall these reactions are
      much more positive than is widely assumed. We conclude that much existing
      research on community reaction to AIDS neglects both a rich body of social theory
      on stigma and a strong tradition of population-based empirical research in
      sociology. Much existing research also fails to adequately distinguish between
      key aspects of the social settings where most AIDS cases occur and the social
      settings where most of the stereotypes surrounding AIDS-related stigma have
      originated. A closer marriage between empirical and theoretical approaches to
      social stigma is required to advance our understanding of this critically
      important dimension of the AIDS epidemic.

PMID- 16433284
TI  - Transnationalism as a motif in family stories.
AB  - Family stories have long been recognized as a vehicle for assessing components of
      a family's emotional and social life, including the degree to which an immigrant
      family has been willing to assimilate. Transnationalism, defined as living in one
      or more cultures and maintaining connections to both, is now increasingly common.
      A qualitative study of family stories in the family of those who appear
      completely "American" suggests that an affiliation with one's home country is
      nevertheless detectable in the stories via motifs such as (1) positively
      connotated home remedies, (2) continuing denigration of home country "enemies,"
      (3) extensive knowledge of the home country history and politics, (4) praise of
      endogamy and negative assessment of exogamy, (5) superiority of home country to
      America, and (6) beauty of home country. Furthermore, an awareness of which model
      -assimilationist or transnational--governs a family's experience may help clarify
      a clinician's understanding of a family's strengths, vulnerabilities, and mode of
      framing their cultural experiences.

PMID- 16433285
TI  - Emotional transnationalism and family identities.

PMID- 16433286
TI  - Migrating across literature, stories, and family therapy.

PMID- 16433287
TI  - Indirect pathways between depressive symptoms and marital distress: the role of
      conflict communication, attributions, and attachment style.
AB  - Previous studies have focused on concomitants of depression and marital distress
      in order to help explain the relationship between the two, suggesting that
      several variables, such as conflict communication, attributions, and attachment
      style, are associated with depression, marital distress, or both. Our contention
      is that the selected variables may be important mediators (hypothesis 1) or
      moderators (hypothesis 2) of the concomitance between depression and marital
      adjustment, exploring the direct and indirect ways in which depressive symptoms
      and marital adjustment are related. In total, 415 heterosexual couples were
      recruited, and a series of regression analyses was conducted to test our
      hypotheses separately for men and women. Results indicated that demand
      withdrawal, avoidance, causal attributions, and secure, ambivalent, and avoidant
      attachment mediated the relation between depressive symptoms and marital
      adjustment in the female sample, whereas constructive communication and causal
      and responsible attributions were significant mediators of men's levels of
      depressive symptoms and marital adjustment. In addition, avoidance and secure
      attachment moderated the association between depressive symptoms and marital
      adjustment in the female sample, and causal attributions were significant
      moderators of the association between depressive symptoms and marital adjustment
      for men. Several conclusions and implications for theory and future research are
      discussed.

PMID- 16433288
TI  - Intergenerational transmission of marital quality across the transition to
      parenthood.
AB  - One of the most frequently reported changes across the transition to parenthood
      is a decline in marital quality after the birth of a first baby. Experiences in
      the family of origin may influence the trajectory of marital quality. Our study
      aimed to investigate the impact of recollections of family-of-origin marriage on
      marital quality (self-reports and clinical evaluation) from pregnancy to 1 year
      after the birth of a first child. A total of 62 first-time parents completed
      questionnaires (self-reported marital satisfaction) and clinical interviews
      (clinical evaluation of couples' dialogue quality). Although self-reported
      marital satisfaction and observed dialogue quality were highly associated, only
      self-reported marital satisfaction declined from pregnancy to 1 year after birth.
      This decrease was partly due to very high marital satisfaction during pregnancy.
      Different trajectories for self-reported marital satisfaction and observed
      dialogue quality were found for participants with recollections of low-, average
      , and high-quality family-of-origin marriage. A structural equation model showed
      that participants who recollected a negative quality in their parents'
      relationship reported more negative changes in the quality of their own
      marriages. There seems to be an intergenerational transmission of marital quality
      that comes to light when couples are challenged by the birth and rearing of a
      baby.

PMID- 16433289
TI  - Healing elements of therapeutic conversation: dialogue as an embodiment of love.
AB  - From our Bakhtinian perspective, understanding requires an active process of
      talking and listening. Dialogue is a precondition for positive change in any form
      of therapy. Using the perspectives of dialogism and neurobiological development,
      we analyze the basic elements of dialogue, seeking to understand why dialogue
      becomes a healing experience in a network meeting. From the perspective of
      therapist as dialogical partner, we examine actions that support dialogue in
      conversation, shared emotional experience, creation of community, and creation of
      new shared language. We describe how feelings of love, manifesting powerful
      mutual emotional attunement in the conversation, signal moments of therapeutic
      change.

PMID- 16433290
TI  - The therapist's self in dialogical family therapy: some ideas about not-knowing
      and the therapist's inner conversation.
AB  - In this article, the focus is on the therapist's self, which will be in line with
      Bakhtin's thinking, viewed as a dialogical self. First, the dialogical view of
      the self is situated in the context of psychology's traditional focus on the
      individual self. Then, leaning on Bakhtin and Volosinov, the self is described as
      a dialogue of multiple inner voices. Some of the implications of this concept for
      family therapy practice are examined, focusing especially on the therapist's
      participation in the therapeutic process and on the therapist's inner
      conversation. The author argues that not-knowing does not only refer to the
      therapist's receptivity and respect but also implies that the therapist is aware
      of his or her experience and reflects on how his or her inner conversation might
      inform and enrich the therapeutic conversation. Finally, these ideas are
      illustrated with a brief clinical vignette.

PMID- 16433291
TI  - Myths about "not-knowing".

PMID- 16433292
TI  - Molecular handles for the mechanical manipulation of single-membrane proteins in
      living cells.
AB  - We have developed a procedure to selectively biotinylate a specific membrane
      protein, enabling its attachment to external force probes and thus allowing its
      mechanical manipulation within its native environment. Using potassium channels
      as model membrane proteins in oocytes, we have found that Maleimide-PEG3400
      biotin is the crosslinker with highest conjugation selectivity and accessibility
      to external probes. Neutravidin-coated beads provide for directed attachment
      while avoiding nonspecific interactions with the cell. The technology was
      successfully tested by mechanical manipulation of biotinylated extracellular
      residues of channels in oocytes using an atomic force microscope under conditions
      which preserve function of the channels. Binding forces of approximately 80 pN at
      100 nN/s were measured.

PMID- 16433293
TI  - Electrode microchamber for noninvasive perturbation of mammalian cells with
      nanosecond pulsed electric fields.
AB  - Nanosecond pulsed electric fields can pass through the external membrane of
      biological cells and disturb fast-responding intracellular structures and
      processes. To enable real-time imaging and investigation of these phenomena, a
      microchamber with integral electrodes and optical path for observing individual
      cells exposed to ultrashort electric pulses was designed and fabricated utilizing
      photolithographic and microelectronic methods. SU-8 photoresist was patterned to
      form straight sidewalls from 10 to 30 microm in height, with gold film deposited
      on the top and sidewalls for conductive, nonreactive electrodes and a uniform
      electric field. Channel dimensions (10-30 microm x 100 microm x 12 000 microm)
      are suitable for observations of mammalian cells during nanosecond, megavolt-per
      meter pulsed electric field exposure. Experimental studies utilizing the
      electrode microchamber include live-cell imaging of nanoelectropulse-induced
      intracellular calcium bursts and membrane phospholipid translocation.

PMID- 16433294
TI  - 3-D numerical study on the induced heating effects of embedded
      micro/nanoparticles on human body subject to external medical electromagnetic
      field.
AB  - Advancement of the recent micro/nanotechnology stimulates the renaissance of
      using magnetic micro/nanoparticles embedded in tissues for the target tumor
      hyperthermia. However, there is a strong lack of quantitative understanding of
      the temperature profiles thus induced by the applied external electromagnetic
      (EM) field, which may impede the successful operation of this therapy. In the
      current study, the three-dimensional quasi-steady-state EM field and transient
      tissue temperature behavior induced by two planar electrodes were numerically
      investigated. Detailed computations indicated that nanoparticles exhibit an
      extraordinary highly focused heating on target tumor tissue, which is much
      stronger than that in the surrounding areas. This heating effect depends heavily
      on the properties of the magnetic nanoparticles, which may vary appreciably for
      different samples depending on their particle sizes and microstructures. The
      effect of micro/nanoparticle concentration, heating area, and the frequency and
      strength of the external alternating EM field were also tested. Moreover, a
      criterion to determine the appropriate particle concentration thermally important
      for medical treatment was established. Given accurate thermal and EM parameters
      for cancerous tissue embedded with nanoparticles, the current model could
      possibly be applied in the hyperthermia treatment planning and help optimize the
      surgical procedures.

PMID- 16433295
TI  - Equivalence-set genes partitioning using an evolutionary-DP approach.
AB  - Computation of transitive-closure equivalence sets has recently emerged as an
      important step for building static and dynamic models of gene network from DNA
      sequences. We present an evolutionary-DP approach in which dynamic programming
      (DP) is embedded into a genetic algorithm (GA) for fitness function evaluation of
      small equivalence sets (with m genes) within a large-scale genetic network of n
      genes, where n > m. This approach reduces a computation-intensive optimal problem
      of high dimension into a heuristic search problem on nCm candidates. The DP
      computation of transitive closure forms the basic fitness evaluation for
      selecting candidate chromosomes generated by GA operators. By introducing bounded
      mutation and conditioned crossover operators to constrain the feasible solution
      domain, small transitive-closure equivalence sets for large genetic networks can
      be found with much reduced computational effort. Empirical results have
      successfully demonstrated the feasibility of our GA-DP approach for offering
      highly efficient solutions to large scale equivalence gene-set partitioning
      problem. We also describe dedicated GA-DP hardware using field programmable gate
      arrays (FPGAs), in which significant speedup could be obtained over software
      implementation.

PMID- 16433296
TI  - Representation and modeling of protein surface determinants.
AB  - Surface characterization of peptides may provide useful information about
      functionality and potential interactions with other molecules. A description of a
      protein site through a surface that models the shape conferred by the exposed
      residues is an effective tool for the analysis and the modeling of proteins that
      may highlight similarities and relationships not detectable through comparisons
      at level of primary, secondary, and tertiary structure. This study concerns the
      development of a tool that extracts the residues that concur to the shape
      modeling of the surface of a protein or a portion of it. This task is
      accomplished without taking into account the order of the amino acids in the
      primary structure, but only according to the selection of a portion of the
      protein indicated through geometric parameters or an explicit list of amino acids
      belonging to the site of interest. Both in the case of an entire protein and in
      the case of a portion of it, the method provides the mesh that models the surface
      described by the exposed residues that constitute the external envelope. The
      developed tool which allows the extraction of the exposed residues, and thus of
      the potential function determinants, is applied to identify the amino acids that
      concur to the structural interaction in several protein complexes.

PMID- 16433298
TI  - Freedom.

PMID- 16433299
TI  - I must go public with an issue that may make me a pariah amongst my fellow
      members of organized dentistry.

PMID- 16433300
TI  - American Board of Forensic Odontology: promotion of the use of thermoplastic
      material to aid in the identification of unidentified human remains.

PMID- 16433301
TI  - Oral pathology quiz #49. Case number 1. Florid cemento-osseous dysplasia.

PMID- 16433302
TI  - Oral pathology quiz #49. Case number 4. Melanocytic nevus.

PMID- 16433303
TI  - Infection control corner: hand hygiene.

PMID- 16433304
TI  - Malignant ameloblastoma of the mandible. A review of definitions and report of a
      case.

PMID- 16433305
TI  - [The centenary of Wassermann reaction--the future of serological diagnosis of
      syphilis, up-to-date studies].
AB  - One hundred years after the discovery of the infectious agent of syphilis and
      implementation of the first serological test for the diagnosis of syphilis,
      important progress in the evaluation of host immune response against Treponema
      (T.) pallidum infection has been made. The paper focuses on the new modifications
      of non-treponemal tests (the use of synthetic cardiolipin and lecithin in
      Venereal Disease Research Laboratory--VDRL test and the application of the VDRL
      antigen to immunoenzymatic assays) as well as of treponemal tests. Original
      treponemal antigens are replaced by recombinant and synthetic antigens (TpN44,5-
      TmpA, TpN15, TpN17 and TpN47) and by antigens obtained after sequencing of the
      complete T. pallidum genome (Tp0453, Tp0257 and Tp92) in modifications of
      immunoenzymatic assays. The new diagnostic strategy, namely the examination of
      the number of cells producing T. pallidum specific antibodies is also presented.
      Despite the progress achieved in studies on humoral response in syphilis during
      last years, the practical application of new tests in diagnosis of the infection
      requires further studies.

PMID- 16433306
TI  - [Persistence of hepatitis B virus in children after interferon-alpha therapy
      despite the seroconversion in HBsAg/anti-HBs system].
AB  - OBJECTIVE: The aim of our study was to assess: (1) whether seroconversion to IgG
      anti-HBs, induced by IFN-alpha therapy in children with chronic active hepatitis
      B, is maintained 4-10 years after treatment; and (2) whether HBV-DNA is present
      in circulation despite the synthesis of anti-HBs. METHODS: Serum samples were
      collected from 38 patients and serological markers of HBV were determined in each
      of them. HBV-DNA was determined by PCR in anti-HBs positive sera. Serum samples
      obtained from 19 subjects with a complete spontaneous seroconversion after acute
      HBV served as controls. RESULTS: Four to 10 years after therapy, anti-HBs were
      present in ca. 97.4% patients with GMT value of 775 IU/L vs 127 IU/L found in
      controls. HBsAg was found in 2/38 subjects. In 13 out of 37 patients (35.1%) free
      and/or bound HBV-DNA was present. CONCLUSIONS: This study showed that
      seroconversion induced by IFN-alpha may not be a sustained phenomenon. HBV-DNA
      may persist for a long time after therapy despite the anti-HBs synthesis.

PMID- 16433308
TI  - [Viral hepatitis type C among medical workers in Silesian voivodeship in years
      1996-2003].
AB  - Viral hepatitis is the most frequent occupational disease among medical workers
      in Poland. It has been estimated on 72% of all work-related infection diseases
      diagnosed in the year 2001, and was hepatitis C. The aim of the study was to
      estimate incidence of viral hepatitis type C among medical workers in Silesian
      voivodeship in years 1996 to 2003. The source of our data was standardized
      documents of occupational diseases collected in sanitary-epidemiological centers
      in the voivodeship. The highest incidence was reported among auxiliary workers
      (48/10,000) and laboratory staff (46/10,000). The smallest incidence of hepatitis
      type C was achieved for nurses and midwives (18/10,000). Obtained results
      revealed a large county-to-county variation in HCV incidence and simultanously
      increase of incidence.

PMID- 16433309
TI  - [Procedure in case of exposure of hospital's workers to HBV, HCV and HIV].
AB  - The aim of this study was to show our own experiences in the treatment our
      hospital's workers after the exposition of potentially infectious material. The
      register of the occupational exposition was established on 1st January 2001. 43
      cases of occupational exposition to potentially infectious material were noted
      down, since the beginning of the observation to 31st October 2004. The persons
      who were injured, represented different professional groups: 9 physicians, 19
      section nurses, 13 operative nurses and 3 maintenance workers. The exposition was
      caused by needle pricks during blood collection or injections (34 cases), as a
      result of a scalpel or other surgical instrument cut (2 cases), a splash of
      infectious material on the skin and conjunctivae (4 cases) and in the singular
      cases as a result of a bite by a stimulated patient, a medical waste cut in a
      rubbish bag or the hospital equipment. It was determined in the immunological
      examinations that among patients being the source of infection were: 1 person
      HBsAg(+), 5 persons anti-HCV(+), 37 persons HbsAg (-), 33 persons anti-HCV(-) and
      5 persons HBsAg(?) and HCV(?). One medical unvaccinated worker was exposed to the
      HBsAg(+) blood. The specific treatment was administered by the application of 1
      dose of anti-HBs immunoglobulin and realization of a series of protective
      vaccinations against HBV. 4 persons are being observed due to an exposition to
      HCV(+) blood. In all cases until now the treatment has been finished without a
      diagnosis of the occupational infection.

PMID- 16433307
TI  - [Pegylated interferon-alfa 2a with ribavirin in chronic viral hepatitis C (final
      report)].
AB  - We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg
      IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label
      programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha
      2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological
      response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of
      follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype
      1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was
      55.7%. A higher SVR rate was obtained in treatment-naive patients (58.7%) than in
      relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1%
      and 88.5%, respectively (p<0.001). There were significant higher SVR rates in
      patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs
      by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased
      significantly during treatment, but returned to baseline after the end of
      treatment. ALT levels decreased significantly during treatment in patients with
      and without an SVR. 38.4% of patients experienced adverse events like
      neutropenia, anemia, thrombocytopenia, and other. There was one death (severe
      thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly
      genotype 1 population was 55.7%. SVR rates were significantly higher in treatment
      naive patients, those with non-1 genotypes, and in patients with lower baseline
      fibrosis scores.

PMID- 16433310
TI  - [Susceptibility of the bacteria isolated from samples of clinical material in
      Poland in 1998 to selected chemotherapeutics and antibiotics--the analysis of the
      questionnaire findings. I. Susceptibility of staphylococci].
AB  - The work has been undertaken in order to attain detailed information on the
      antibiotic sensitivity of the identified microorganisms from different clinical
      material derived from inpatients, outpatients and healthy people, on various
      regions of Poland in 1998. Approprite questionnaires (cards) were sent to each
      sanitary-epidemiological stations throughout Poland. Received 28619 cards, from
      44 Public Health Service laboratories, allowed to create a computerized data base
      in Department of Bacteriology in National Institute of Hygiene in Warsaw.
      Staphylococci were the most frequent etiologic pathogen isolated from the
      clinical material--24,7%. Among them, there were: S. aureus--75,8%, S.
      epidermidis--9,7%, unidentified coagulase negative staphylococci (CNS)--9,2% and
      S. saprophyticus--5,1%. 71,6% of staphylococci strains derived from non-hospital
      material and 26,7% from hospital material. Staphylococci strains isolated from
      inpatients specimens were more resistant to antibiotics than those from
      outpatients specimens. The highest resistance, among both hospital and non
      hospital strains, was exhibited to penicillin (70-100%) and tetracycline
      (approximately 50%); the lowest to: glycopeptides, ciprofloxacin,
      trimethoprim/sulfametoxazole, nitrofurantoin and gentamicin. Staphylococci
      isolated from various clinical specimens differed in their antibiotic resistance.
      The percentages of coagulase-negative staphylococci strains resistant to the
      antibiotics used were higher than of S. aureus strains. On the average 34% of S.
      aureus strains were methicillin-resistant (MRSA); but depending on specimens were
      isolated from, it ranged from 24% of MRSA strains for ear and nose swabs to 70%
      of MRSA strains for feaces samples. Among MRSA strains the percentage of
      resistance to other antibiotics was a few time higher than among MSSA strains.
      The territorial distribution of staphylococci strains resistance to various
      antibiotics in Poland is not uniform.

PMID- 16433311
TI  - [Role of cytokines and pathogen associated molecular pattern receptors in
      sepsis].
AB  - Sepsis is life-treating state caused by overwhelming inflammatory response to
      infection accompanied by disregulation of non-specific immunity mechanisms. In
      this review we discussed influence of Gram-positive and Gram-negative bacterial
      virulence factors, cytokines as well as pathogen associated molecular pattern
      receptors (TLR-toll like receptors, peptydoglican recognition proteins,
      nucleotide binding oligomerization domains, triggering receptor expressed on
      myeloid cells-1) on the development and course of sepsis.

PMID- 16433312
TI  - [Procalcitonin (PCT) concentration in cerebrospinal fluid and plasma of patients
      with purulent and lymphocytic meningoencephalitis--own observations].
AB  - The aim of the study was assessment of usefulness of cerebrospinal fluid (CSF)
      and plasma procalcitonin concentration estimation in differential diagnosis of
      neuroinfections in adults. Examinations were carried out in 17 subjects with
      purulent, bacterial meningoencephalitis and in 16 patients with lymphocytic
      meningitis. In all individuals CSF and plasma PCT concentrations were assessed on
      the 1st day of hospitalization. In patients with purulent, bacterial
      meningoencephalitis mean CSF concentration was 0,63 ng/mL, mean plasma PCT
      concentration--9,97 ng/mL. Mean CSF PCT concentration in patients with
      lymphocytic meningitis was 0,23 ng/mL and mean plasma PCT concentration--0,27
      ng/mL. Differences of mean PCT concentrations between both groups of patients
      were statistically significant: CSF--p<0,05 and plasma--p<0,01. Obtained results
      indicate usefulness of plasma PCT concentration estimation in differential
      diagnosis of neuroinfections in adults. Cerebrospinal fluid PCT concentration
      seems to be of lesser importance in differential diagnosis of neuroinfections,
      but value of this parameter often correlates with the severity of the clinical
      state of the patients and may be taken into consideration in prognosis of the
      course and outcome of the bacterial meningoencephalitis.

PMID- 16433313
TI  - [Clostridium difficile toxin A and other enteropathogens in stool specimens of
      children hospitalized due to acute diarrhoea].
AB  - A total of 74 fresh stool specimens obtained from children with acute diarrhoea
      (43) and without diarrhoea (31) were examined simultaneously for bacteria
      pathogens (culture methods) and for Clostridium difficile toxin A (Oxoid Toxin A
      Kits) and enteric viruses (only diarrhoeal samples) (Slidex Rota-Adeno Kits;
      bioMcrieux). One (49%) or dual with C. difficile (23%) enteric pathogens
      associated with community-acquired diarrhoea (58% bacteria and 14% viruses) in 31
      (72%) children were recognized. Clostridium difficile associated diarrhoea (CDAD)
      (18,6%) and Salmonella enterica subsp. enterica serovar Enteritidis (16,3%) the
      most commonly were observed. Children were considered to have CDAD if they met
      special criteria such as the positive test for C. difficile toxin A, the presence
      of diarrhoea for at least 2 days and no other documented enteric pathogens. It
      was be found that antibiotic usage in the previous 3 weeks as a main risk factor
      for CDAD not be frequent (only 2/8 CDAD). The frequency of C. difficile toxin A
      detection in the diarrhoeal stool specimens from children treated or not treated
      with antibiotics was comparable (p>0,05); this same observed when stool specimens
      from children without diarrhoea were tested. The frequency of toxin A detection
      in stool specimens from children with acute diarrhoea (41,9%) and without
      diarrhoea (54,8%) was comparable (p>0,05) also. In conclusion, we recommended
      detection of toxin A by C. difficile toxin A Test as the rapid screening in
      diarrhoeal stool specimens only because the high predictive value of a negative
      test and the high sensitivity for CDAD with special criteria were found.

PMID- 16433314
TI  - [Chlamydia trachomatis: etiopathogenesis and diagnosis of infection].
AB  - Infection of genito-urinary tract, caused by C. trachomatis are common worldwide.
      In countries, where screening diagnosis and effective treatment programmes were
      introduced decreasing level of infections and their complications were described.
      Because C. trachomatis is an obligate intracellular bacterium, very often
      infections are asymptomatic, although complications of symptomatic and
      asymptomatic infections are the same. Classically diagnosis of C. trachomatis
      infection is made based on culture in Mc Coy cells. C. trachomatis antigen is
      detected by DIF and EIA. Amplification technique play very important role in
      diagnosis of C. trachomatis infection. In this article we analysed laboratory
      diagnostic tools of urogenital chlamydiosis based on literature data and own
      experiences.

PMID- 16433316
TI  - [Case of typhoid fever in 43 old male].
AB  - The disease of 43 years old man, who was being taken in internal ward to
      diagnosis because of fever, was presented. In bacteriological culture Salmonella
      Typhi were kept. For reason the isolation was impossible on internal department,
      patient was conveyed to contagious department. As a result of carried out
      epidemiological inquiry, it turned out the man's infectious was coused by
      permanent carrier of typhoid fever.

PMID- 16433315
TI  - [Reported infectious diseases within the area of the activity of PSSE Zwolen
      between 2000-2004].
AB  - The aim of the work was to review and evaluate activity of Primary Health Care
      Institutions in terms of binding regulations concerning reported infectious
      diseases and infections. In order to carry out the evaluation, the number of
      cases diagnosed in Primary Healthcare Institutions PHI (number of cases of
      infectious diseases registered in daily records according to IC D10 was compared
      to the number of cases reported to County Sanitary Inspector between 2000-2004.
      Analyzed figures of morbidity and notification to PSSE reveal that not all the
      subjected cases, were registered and reported by Health care Institutions.
      Diseases that have been subjected to legal notification for many years were
      reported more frequently than those subjected to notification since 2002 (ew
      Parliamentary Act in force). In order to examine the problem of non-reported
      infectious diseases further activities of other Sanitary and Epidemiology
      Stations need to be inspected.

PMID- 16433317
TI  - [Insulin resistance indices in population-based study and their predictive value
      in defining metabolic syndrome].
AB  - In clinical studies insulin resistance, the main factor of the Metabolic Syndrome
      (MS), is determined directly by metabolic clamp technique, while in
      epidemiological studies is estimated on the basis of indices calculated from oral
      glucose tolerance test glycemia and insulinemia. The aim of the study was to find
      out which insulin resistance indicator best predicts the risk of the MS. MATERIAL
      AND METHODS: The study population consisted of 2673 inhabitants of Krakow, aged
      35-75 years, who participated in the "Polish Multicenter Study on Diabetes
      Epidemiology". Fasting insulin, HOMA-IR, QUICKI and Matsuda's index were
      determined for all subjects. Insulin resistance was defined as the cutoff values
      for the population with normal glucose tolerance and with BMI < 25 kg/m2.
      RESULTS: All insulin resistance indices were closely correlated (r=0.78-0.98),
      and the frequency of insulin resistance in the general population was similar
      (47%-54%), however the highest prevalence of insulin resistance was observed when
      Matsuda index was used. The risk of insulin resistance, increased with the
      category of glucose tolerance, and was the highest when Matsuda index was used.
      The MSWHO was observed in 42% to 45% of the studied population and the predictive
      value of insulin resistance indices were similar when using WHO criteria. The
      highest sensitivity in the MSNCEP identification was observed when Matsuda index
      was used. Matsuda index had also the highest sensitivity to diagnose MSNCEP as
      compared with the remaining insulin resistance indices. CONCLUSIONS: The study
      insulin resistance indices have a similar value in predicting the MSWHO while
      Matsuda index predicts best the MSNCEP. Matsuda index as well predicts best the
      risk of insulin resistance. This argues in favor of using oral glucose tolerance
      test to estimate risk for diabetes mellitus and cardiovascular disease.

PMID- 16433318
TI  - [Validity and reliability of Polish adaptation of Yale Global Tic Severity Scale
      (YGTSS) in a study of Warsaw schoolchildren aged 12-15].
AB  - The aim of the study was to assess the reliability and validity of the Polish
      adaptation of the YGTSS scale in a study screening a population of 1579
      schoolchildren for tic disorders. The scale was administered to 60 children with
      diagnosis of a tic disorder (15 had transient tic disorder; 37 had chronic tic
      disorder, and 8 had Tourette disorder). Reliability was computed using Cronbach's
      alpha coefficient and by evaluation of its internal consistency. Theoretical
      validity of the scale was evaluated using factor analysis. The computed
      Cronbach's alpha coefficient for the YGTSS scale was 0.73. All items (except
      phonic tic complexity) highly correlated with their respective subscale scores.
      Factor analysis of YGTSS revealed two principal components that recombined the
      items into categories identical to motor and vocal tic subscales. The overall
      impairment item loading corresponded to motor tic subscale. The YGTSS scale used
      in a population sample of 12-15 year old schoolchildren has acceptable validity
      and reliability. Additional study testing psychometric parameters of the scale
      could be beneficial, involving subjects with Tourette syndrome with wider age
      range and interrater agreement

PMID- 16433319
TI  - [Gender and HIV/AIDS prevention].
AB  - The sociocultural gender norms that interfere with vulnerability to HIV/AIDS in
      global and Polish context are discussed. The issue of gender related HIV/AIDS
      vulnerability in Poland is underestimated. Existing data on unemployment rate and
      average wages seems to indicate that socioeconomic status of women in Poland is
      rather low and create social suspectibility to HIV infection. Some programmatic
      and policy recommendations to reduce individual risk and vulnerability of women
      and men are presented.

PMID- 16433320
TI  - [Parents' unemployment, selected life conditions, adolescents' wellbeing and
      perceived health].
AB  - Unemployment in Poland is one of the most negative outcomes of the economical
      transformations taking place in the last decade of the XX and first years of the
      XXI century. Therefore, the study on an influence of parents' unemployment upon
      adolescents' life conditions and health was undertaken in Health Promotion and
      Postgraduate Training Department of the National Institute of Hygiene. The data
      were collected from randomly selected sample of 783 students aged 14-15 years
      attending to ten private and public secondary schools (gymnasiums) in Warsaw. A
      part of the questionnaire elaborated in Health Promotion and Postgraduate
      Department covered information about negative life events, which had occurred in
      the previous year, also about a loss of the job by father or mother. The self
      assessment of health, and physical and psychical wellbeing measured the perceived
      health. The study showed that significantly higher percentage of the students,
      whose father or mother had lost a job in the previous year, noticed also
      occurrence of father and mother health disorders, lack of support from father and
      mother, frequent quarrels between parents, too much of home duties, worsening a
      housing conditions, lack of possibilities to travel away on vacation and lack of
      own money. The differences were higher, if both the parents were unemployed.
      Moreover, the children of unemployed parents significantly lower assessed their
      health, and physical and psychical wellbeing. It is necessary to help immediately
      the students, whose parents are unemployed, with financial and psychological
      support in frame of the programmes of unemployment overcoming.

PMID- 16433321
TI  - [Calculating costs of premature infants' intensive care in the United States of
      America, Canada and Australia].
AB  - Although advanced neonatal care technology has contributed to significant decline
      in mortality of premature infants, it has also resulted in rising costs of
      hospitalization. Premature infants constitute 4% to 6% of all newborns treated
      annually in Neonatal Intensive Care Units (NICUs) and that is why the cost of
      prematurity determines considerable financial burden on health care in each
      country. In Poland research concerning costs of neonatal intensive care have not
      been conducted so far. The object of this paper is to review world-wide
      literature on that subject, particularly taking into consideration methods of
      estimating costs and economic analysis, such as cost-benefit analysis, cost
      effect analysis and cost-utility analysis. The results of studies undertaken in
      the United States of America, Canada and Australia have been presented. Results
      of review indicate the strong relationship between high costs and small
      gestational age or low birth-weight of newborns. As no research in this area has
      been conducted in Poland so far, it seems to be crucial to estimate costs of
      neonatal intensive care of premature infants in Poland. Precise analysis of main
      factors determining high costs may be helpful in searching for significant
      savings. It would be a useful decision-making tool both for the NICU and the
      hospital managers.

PMID- 16433322
TI  - HBCD: facts and insinuations.

PMID- 16433323
TI  - California's shifting sands.

PMID- 16433324
TI  - Judith Curry. Interview by Paul D Thacker.

PMID- 16433325
TI  - Biodiversity: friend or foe of invasive species?

PMID- 16433326
TI  - EU contemplates first-ever limit on PM2.5.

PMID- 16433327
TI  - U.S. Army Corps of Engineers allows wetlands to go unprotected, GAO finds.

PMID- 16433328
TI  - The long and the short of perfluorinated replacements.

PMID- 16433329
TI  - Probing the enantioselectivity of chiral pesticides.

PMID- 16433330
TI  - Sources, fate and transport of perfluorocarboxylates.
AB  - This review describes the sources, fate, and transport of perfluorocarboxylates
      (PFCAs) in the environment, with a specific focus on perfluorooctanoate (PFO).
      The global historical industry-wide emissions of total PFCAs from direct
      (manufacture, use, consumer products) and indirect (PFCA impurities and/or
      precursors) sources were estimated to be 3200-7300 tonnes. It was estimated that
      the majority (approximately 80%) of PFCAs have been released to the environment
      from fluoropolymer manufacture and use. Although indirect sources were estimated
      to be much less importantthan direct sources, there were larger uncertainties
      associated with the calculations for indirect sources. The physical-chemical
      properties of PFO (negligible vapor pressure, high solubility in water, and
      moderate sorption to solids) suggested that PFO would accumulate in surface
      waters. Estimated mass inventories of PFO in various environmental compartments
      confirmed that surface waters, especially oceans, contain the majority of PFO.
      The only environmental sinks for PFO were identified to be sediment burial and
      transport to the deep oceans, implying a long environmental residence time.
      Transport pathways for PFCAs in the environment were reviewed, and it was
      concluded that, in addition to atmospheric transport/degradation of precursors,
      atmospheric and ocean water transport of the PFCAs themselves could significantly
      contribute to their long-range transport. It was estimated that 2-12 tonnes/ year
      of PFO are transported to the Artic by oceanic transport, which is greater than
      the amount estimated to result from atmospheric transport/degradation of
      precursors.

PMID- 16433331
TI  - Plant uptake of non ionic organic chemicals.
AB  - Plant uptake of organic chemicals is an important process when considering the
      risks associated with land contamination, the role of vegetation in the global
      cycling of persistent organic pollutants, and the potential for industrial
      discharges to contaminate the food chain. There have been some significant
      advances in our understanding of the processes of plant uptake of organic
      chemicals in recent years; most notably there is now a better understanding of
      the air to plant transfer pathway, which may be significant for a number of
      industrial chemicals. This review identifies the key processes involved in the
      plant uptake of organic chemicals including those for which there is currently
      little information, e.g., plant lipid content and plant metabolism. One of the
      principal findings is that although a number of predictive models exist using
      established relationships, these require further validation if they are to be
      considered sufficiently robust for the purposes of contaminated land risk
      assessment or for prediction of the global cycling of persistent organic
      pollutants. Finally, a number of processes are identified which should be the
      focus of future research.

PMID- 16433332
TI  - Application of multimedia models for screening assessment of long-range transport
      potential and overall persistence.
AB  - We propose a multimedia model-based methodology to evaluate whether a chemical
      substance qualifies as POP-like based on overall persistence (Pov) and potential
      for long-range transport (LRTP). It relies upon screening chemicals against the
      Pov and LRTP characteristics of selected reference chemicals with well
      established environmental fates. Results indicate that chemicals of high and low
      concern in terms of persistence and long-range transport can be consistently
      identified by eight contemporary multimedia models using the proposed
      methodology. Model results for three hypothetical chemicals illustrate that the
      model-based classification of chemicals according to Pov and LRTP is not always
      consistent with the single-media half-life approach proposed by the UNEP
      Stockholm Convention and thatthe models provide additional insight into the
      likely long-term hazards associated with chemicals in the environment. We suggest
      this model-based classification method be adopted as a complement to screening
      against defined half-life criteria at the initial stages of tiered assessments
      designed to identify POP-like chemicals and to prioritize further environmental
      fate studies for new and existing chemicals.

PMID- 16433333
TI  - Environmental impact and human health risks of polychlorinated dibenzo-p-dioxins
      and dibenzofurans in the vicinity of a new hazardous waste incinerator: a case
      study.
AB  - The purpose of this study was to assess the environmental impact of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the vicinity of
      a new hazardous waste incinerator (HWI) 4 years after regular operation of the
      facility. A double approach was carried out. The PCDD/F congener profiles
      corresponding to environmental samples, soil and herbage, collected before the
      HWI (baseline) and 4 years after starting regular operations, as well as PCDD/F
      profiles of air emission samples, were compared. The potential health risks
      (carcinogenic and noncarcinogenic) due to PCDD/F exposure were assessed for
      adults and children living in the neighborhood of the facility. Human exposure to
      PCDD/Fs was mainly due to dietary food intake. Comparisons between the PCDD/F
      congener profiles corresponding to the baseline and current surveys, as well as
      data concerning the human health risk assessment, indicate that the HWI in
      question does not cause additional risks to the environment orto the population
      living in the vicinity of the facility.

PMID- 16433335
TI  - Effects of the antithyroid agent propylthiouracil in a partial life cycle assay
      with zebrafish.
AB  - Some ubiquitous pollutants of the aquatic environment, such as PCBs or other
      polyhalogenated aromatic hydrocarbons, may disrupt the thyroid hormone system. In
      a partial life cycle assay with zebrafish (Danio rerio), we studied the effects
      of the reference compound propylthiouracil (PTU) on reproduction, growth and
      development, histopathology of some target tissues, and plasma thyroid hormone
      levels. PTU induced a concentration-dependent increase of egg production with a
      concomitant decrease of mature oocyte size but had no effect on fertilization
      rate or hatching. In F1, serious dysmorphogenesis was found in 4 dph larvae at
      the highest PTU level tested (100 mg/L), and there was a dose-dependent decrease
      in body length and weight at 42 dph (significant at 100 mg/L PTU). At this time,
      there was also a decreased scale thickness, suggesting inhibited metamorphosis,
      detectable at 1 mg/L PTU and higher. PTU also induced activation of the thyroid
      follicles in a concentration-dependent way, in juveniles associated with
      hyperemia in the thyroid area, and depletion of liver glycogen. Effects in adults
      were associated with decreased circulating levels of the thyroid hormones T3 and
      T4. These observations indicate that disruption of the thyroid hormone system may
      affect the fitness of these aquatic organisms. The zebrafish model may contribute
      to the identification of thyroid hormone disrupting activity in water samples and
      also in the interpretation of histological observations in free-ranging fish
      species.

PMID- 16433334
TI  - Landfill-stimulated iron reduction and arsenic release at the Coakley Superfund
      Site (NH).
AB  - Arsenic is a contaminant at more than one-third of all Superfund Sites in the
      United States. Frequently this contamination appearsto resultfrom geochemical
      processes rather than the presence of a well-defined arsenic source. Here we
      examine the geochemical processes that regulate arsenic levels at the Coakley
      Landfill Superfund Site (NH), a site contaminated with As, Cr, Pb, Ni, Zn, and
      aromatic hydrocarbons. Long-term field observations indicate that the
      concentrations of most of these contaminants have diminished as a result of
      treatment by monitored natural attenuation begun in 1998; however, dissolved
      arsenic levels increased modestly over the same interval. We attribute this
      increase to the reductive release of arsenic associated with poorly crystalline
      iron hydroxides within a glaciomarine clay layer within the overburden underlying
      the former landfill. Anaerobic batch incubations that stimulated iron reduction
      in the glaciomarine clay released appreciable dissolved arsenic and iron. Field
      observations also suggest that iron reduction associated with biodegradation of
      organic waste are partly responsible for arsenic release; over the five-year
      study period since a cap was emplaced to prevent water flow through the site,
      decreases in groundwater dissolved benzene concentrations at the landfill are
      correlated with increases in dissolved arsenic concentrations, consistent with
      the microbial decomposition of both benzene and other organics, and reduction of
      arsenic-bearing iron oxides. Treatment of contaminated groundwater increasingly
      is based on stimulating natural biogeochemical processes to degrade the
      contaminants. These results indicate that reducing environments created within
      organic contaminant plumes may release arsenic. In fact, the strong correlation
      (>80%) between elevated arsenic levels and organic contamination in groundwater
      systems at Superfund Sites across the United States suggests that arsenic
      contamination caused by natural degradation of organic contaminants may be
      widespread.

PMID- 16433336
TI  - Mass balance assessment for mercury in Lake Champlain.
AB  - A mass balance model for mercury in Lake Champlain was developed in an effort to
      understand the sources, inventories, concentrations, and effects of mercury (Hg)
      contamination in the lake ecosystem. To construct the mass balance model, air,
      water, and sediment were sampled as a part of this project and other
      research/monitoring projects in the Lake Champlain Basin. This project produced a
      STELLA-based computer model and quantitative apportionments of the principal
      input and output pathways of Hg for each of 13 segments in the lake. The model Hg
      concentrations in the lake were consistent with measured concentrations.
      Specifically, the modeling identified surface water inflows as the largest direct
      contributor of Hg into the lake. Direct wet deposition to the lake was the second
      largest source of Hg followed by direct dry deposition. Volatilization and
      sedimentation losses were identified as the two major removal mechanisms. This
      study significantly improves previous estimates of the relative importance of Hg
      input pathways and of wet and dry deposition fluxes of Hg into Lake Champlain. It
      also provides new estimates of volatilization fluxes across different lake
      segments and sedimentation loss in the lake.

PMID- 16433337
TI  - Natural fluctuations of mercury and lead in Greenland lake sediments.
AB  - Given the current scenario of increasing global temperatures, it is valuable to
      assess the potential influence of changing climate on pollution distribution and
      deposition. In this study we use long-term sediment records from three lakes
      (spanning ca. 1000, 4800, and 8000 years, respectively) from the Greenland west
      coast to assess recent and long-term variations in mercury (Hg) and lead (Pb),
      including stable Pb isotopes (206Pb and 207Pb), in terms of pollution and climate
      influences. The temporal trends in sediment deposited from about the mid-19th
      century and forward are in general agreement with the history of industrial
      emissions at lower latitudes. Therefore, in recent sediment a possible influence
      from changing climate is difficult to assess. However, by using deeper sediment
      layers we show that changes in Greenland climate caused changes in the lake
      influx of material from regional aeolian activity, which resulted in large
      fluctuations in Hg and Pb concentrations and 206Pb/207Pb ratios. The aeolian
      material is primarily derived from glacio-fluvial material with low Hg and Pb
      concentrations and a different isotopic composition. For one of the lakes, the
      fluctuations in Hg concentrations (10 to 70 ng g(-1)) prior to the 19th century
      are equal to the anthropogenic increase in the uppermost layers, suggesting that
      when studying recent concentrations and time trends of pollution in relatively
      low-contaminated areas such as the Arctic, the early natural fluctuations must be
      considered.

PMID- 16433339
TI  - Ambient air concentrations, source profiles, and source apportionment of 71
      different C2-C10 volatile organic compounds in urban and residential areas of
      Finland.
AB  - Ambient air concentrations and source contributions of 71 volatile organic
      compounds (VOCs) including C2-C10 nonmethane hydrocarbons, halogenated
      hydrocarbons, and carbonyls were studied at urban and residential sites in
      Finland. On the basis of the emission profile and concentration measurements, the
      contributions of different sources were estimated using a chemical mass balance
      (CMB) receptor model. It was shown that it is possible to apply CMB in the case
      of a large number of different compounds with different properties. However, the
      performance of the model varies significantly for the different compounds.
      According to the CMB analysis, major sources for these VOCs at the urban site
      were traffic and distant sources. At the residential site, the contribution due
      to traffic was minor while distant sources, liquid gasoline, and wood combustion
      made higher contributions. However, different compound groups or compounds were
      found to have totally different sources. It was also shown that a biogenic
      compound, isoprene, also has significant anthropogenic sources and that at some
      locations wood combustion can be an important source for some VOCs usually
      considered as traffic-related compounds (e.g., benzene).

PMID- 16433338
TI  - Volatilization of the pesticides chlorpyrifos and fenpropimorph from a potato
      crop.
AB  - Volatilization of pesticides from crops in the field can be an important emission
      pathway. In a field experiment with characterization of meteorological
      conditions, the pesticides chlorpyrifos and fenpropimorph were sprayed onto a
      potato crop, after which concentrations in the air and on/in the plants were
      measured. Rates of volatilization were estimated with the aerodynamic profile
      (ADP), energy balance (EB), relaxed eddy accumulation (REA), and plume dispersion
      (PD) methods. The volatilization rates obtained with the ADP and EB methods were
      similar, while some rates obtained with the REA and PD methods in the initial
      period were lower. Cumulative volatilization of chlorpyrifos during daylight
      hours (ADP and EB methods) was estimated to be about 65% of the dosage. By far
      the majority of this volatilization occurred in the first few days. Competing
      processes at the plant surface had a considerable effect on the dissipation of
      fenpropimorph, so cumulative volatilization during daylight hours was estimated
      to be only 7% of the dosage. Plant surface residues were higher than would
      correspond with the volatilization rate, indicating that penetration into the
      leaves had occurred.

PMID- 16433340
TI  - PCB congeners and dechlorination in sediments of Lake Hartwell, South Carolina,
      determined from cores collected in 1987 and 1998.
AB  - Four sediment cores were collected from Lake Hartwell, SC, in 1987 and 1998 and
      analyzed for polychlorinated biphenyl (PCB) congeners. Total PCBs ranged from -0
      to 58 microg/ g. Positive matrix factorization (PMF) was applied to the data sets
      to determine PCB source profiles. Two factors were determined for each data set.
      One factor resembled the original estimated PCB mixture of 80% Aroclor 1016 and
      20% Aroclor 1254 and the other factor was a dechlorinated version of the mixture.
      Evidence of a dechlorination plateau is apparent from the PMF loading solutions
      because the dechlorinated congener profiles do not change from 1987 to 1998,
      butthe contribution to the profile from the dechlorinated factor increases from
      73% (1987) to 87% (1998). PMF source contributions and plots of PCB concentration
      versus congener for individual samples provide evidence of enhanced
      dechlorination at high concentrations. After source apportionment an anaerobic
      dechlorination model was applied to the dechlorinated source profiles to quantify
      possible dechlorination pathways. It was found that dechlorination process M,
      extended to target biphenyl rings with up to six chlorines, provided the best fit
      for an individual process, and M + Q provides the best fit for combined
      processes, although M + LP also provides a similarfit. Process LP targets the
      higher chlorinated congeners and appears to dechlorinate PCBs in the sediments
      initially.

PMID- 16433341
TI  - PCB congeners and dechlorination in sediments of Sheboygan River, Wisconsin,
      determined by matrix factorization.
AB  - Nine sediment cores were collected from the Sheboygan River Inner Harbor, WI, and
      analyzed for polychlorinated biphenyl (PCB) congeners. Total PCBs ranged from
      approximately 0 to 161 mg/g. Positive matrix factorization (PMF) was applied to
      the PCB data setto determine source profiles. Two factors were determined to be
      significant. One factor resembled the original approximated PCB mixture of 50%
      Aroclor 1248 and 50% Aroclor 1254 and the other factor was a dechlorinated
      version of the mixture. An anaerobic dechlorination model was applied to the
      dechlorinated source profiles to quantify possible dechlorination pathways. It
      was found that dechlorination process H' provided the best fit for an individual
      process, and H' + M provides the best fit for combined processes. PMF source
      contributions, and plots of PCB concentration versus congener for individual
      samples, provide evidence of enhanced dechlorination at high concentrations (>40
      ppm) and small amounts of dechlorination at low concentrations (<3 ppm). In
      addition, downward migration of lower chlorinated PCBs in core SR1a has occurred.
      Remediation dredging in the Upper Sheboygan River in 1989 and 1990 reintroduced
      PCBs to the water column and selective transport of PCB 18 is observed in core
      SR7.

PMID- 16433342
TI  - De novo formation of chloroethyne in soil.
AB  - To date, chloroethyne in the environment has been proposed to occur as a reactive
      intermediate during the reductive dechlorination of tri- and tetrachloroethene
      with zerovalent metals. Such artificial conditions might possibly be found at
      organohalide-contaminated sites that are surrounded by remediation barriers made
      of metallic iron. In this paper, it is shown that the highly reactive
      chloroethyne is also a product of natural processes in soil. Soil air samples
      from three differentterrestrial ecosystems of Northern Germany showed significant
      chloroethyne concentrations, besides other naturally produced monochlorinated
      compounds, such as chloromethane, chloroethane and chloroethene. Measured amounts
      range from 5 to 540 pg chloroethyne in air purged from 1 L of soil. A possible
      route of chloroethyne formation in soil is discussed, where chloroethyne is
      probably produced as a byproduct of the oxidative halogenation of aromatic
      compounds in soil. A series of laboratory studies, using the redox-sensitive
      catechol as a discrete organic model compound, showed the formation of
      chloroethyne when Fe3+ and hydrogen peroxide were added to the system. We
      therefore propose that the natural formation of chloroethyne in soil proceeds via
      oxidative cleavage of a quinonic system in the presence of the ubiquitous soil
      component chloride.

PMID- 16433343
TI  - Field measurements of aerosol particle dry deposition on tropical foliage at an
      urban site.
AB  - This paper presents dry deposition of major ions on tropical foliage (leaves of
      Ashok (Polyalthia longifolia) and Cassia (Cassia siamea)) at St. John's, Agra, an
      urban site of tropical India on nonrainy, nondewy, and nonfoggy days. The
      deposition flux was higher on Cassia leaf than Ashok leaf probably due to a
      rougher surface as shown by scanning electron microscopy. Dry deposition of
      cations varies from 0.46 to 12.16 mg m(-2) day(-1) while anions vary from 0.04 to
      3.24 mg m(-2) day(-1). The percentage contribution of alkaline components is
      greater than that of acidic components, indicating the alkaline nature of dry
      deposition. Two-way analysis of variance results reveal significant seasonal
      variation only for K+, SO4(2-), and F-; however, values varied season to season
      for Na+, Ca2+, Mg2+, Cl-, NO3-, and NH4+ also. The large seasonal variation in
      deposition flux may be due to meteorological conditions, diameter of particles,
      and variation in atmospheric level. SO42- and NO3- show significant correlation,
      indicating their origin from similar sources while significant correlation
      between Ca2+ and Mg2+ implies their origin from soil. Poor correlation between
      Ca2+ and SO4(2-), Ca2+ and NO3-, and Mg2+ and SO4(2-) indicates that in addition
      to soil other sources also contribute to dry deposition. Low dry deposition
      fluxes of SO2- and NO3- compared to Ca2+ and Mg2+ may be due to low mass medium
      diameters of SO4(2-) and NO3- and may be due to uptake through the stomatal pores
      abundant on leaf surfaces. Factor analysis was employed to identify the sources.
      F-, Cl, SO4(2-), NO3-, and K+ are grouped together in the first factor,
      indicating their probable contribution from combustion, Ca2+, Mg2+, and NH4+ are
      grouped in factor II, which may be attributed to road dust and soil, and factor
      III includes mainly Na+ and F-, probably contributed from brick-kiln industries.
      Atmospheric concentrations of F-, Cl-, NOs-, SO4(2-), Na+, K+, Ca2+, Mg2+, and
      NH4+ were found to be 0.38, 2.28, 1.31, 2.74, 0.44, 0.59, 1.21, 1.2, and 2.29
      microg m(-3), respectively.

PMID- 16433345
TI  - Comparison of real-world emissions from two-wheelers and passenger cars.
AB  - Passenger cars are the primary means of transportation in Europe. Over the past
      decade, a great deal of attention has therefore been paid to reducing their
      emissions. This has resulted in notable technical progress, leading to
      unprecedentedly low exhaust emissions. In the meantime, emissions from
      motorcycles have been ignored due to their subordinate role in traffic. Even
      though the motorcycle fleet is small in comparison with the car fleet, and logs
      lower yearly mileage per vehicle, their contribution to traffic emissions has
      become disproportionately high. Exhaust emissions of CO, HC, NOx, and CO2 from 8
      powered two-wheelers were measured and compared to previous measurements from 17
      gasoline-powered passenger cars performed at EMPA with the aim of ascertaining
      their relevance. Using exhaust emission ratios from both vehicle types,
      comparisons based on mean unit, mean yearly, and fleet emissions are considered.
      Present-day aftertreatment technologies for motorcycles are not as efficient as
      those for cars. A comparison of mean unit emissions shows that motorcycles exceed
      cars in NOx emissions. All comparisons reveal a significant HC ratio, to the
      detriment of two-wheelers. Overall, the relevance of emissions from powered two
      wheelers is not negligible when compared with modern gasoline-powered passenger
      cars.

PMID- 16433344
TI  - Bridging the gap between macroscopic and spectroscopic studies of metal ion
      sorption at the oxide/water interface: Sr(II), Co(II), and Pb(II) sorption to
      quartz.
AB  - Metal sorption mechanisms were investigated for strontium, cobalt, and lead using
      sodium chloride, sodium nitrate, and sodium perchlorate as background
      electrolytes and quartz as the adsorbent. Spectroscopic analyses of concentrated
      sorption samples were evaluated for their ability to provide insight into the
      controlling sorption process for more dilute systems. For strontium, outer-sphere
      complexes identified using X-ray absorption spectroscopy (XAS) of concentrated
      samples were consistent with macroscopic sorption data collected in more dilute
      systems. XAS results indicated that cobalt formed a new solid phase upon sorption
      to silica. Macroscopic studies of cobalt sorption supported the spectroscopic
      data for total cobalt concentrations of 10(-5) M, regardless of the background
      electrolyte composition or concentration. At a lower total cobalt concentration
      (10(-7) M), adsorption appeared to be the prevailing mechanism of cobalt removal.
      Spectroscopic results suggested that lead adsorbed as an inner-sphere complex on
      silica. The decrease of lead removal with increasing chloride concentration was
      attributed to competition with aqueous lead-chloride complexes, based on
      thermodynamic calculations.

PMID- 16433346
TI  - Effects of dilution on fine particle mass and partitioning of semivolatile
      organics in diesel exhaust and wood smoke.
AB  - Experiments were conducted to examine the effects of dilution on fine particle
      mass emissions from a diesel engine and wood stove. Filter measurements were made
      simultaneously using three dilution sampling systems operating at dilution ratios
      ranging from 20:1 to 510:1. Denuders and backup filters were used to quantify
      organic sampling artifacts. For the diesel engine operating at low load and wood
      combustion, large decreases in fine particle mass emissions were observed with
      increases in dilution. For example, the PM2.5 mass emission rate from a diesel
      engine operating at low load decreased by 50% when the dilution ratio was
      increased from 20:1 to 350:1. Measurements of organic and elemental carbon
      indicate that the changes in fine particle mass with dilution are caused by
      changes in partitioning of semivolatile organic compounds. At low levels of
      dilution semivolatile species largely occur in the particle phase, but increasing
      dilution reduces the concentration of semivolatile species, shifting this
      material to the gas phase in order to maintain phase equilibrium. Emissions of
      elemental carbon do not vary with dilution. Organic sampling artifacts are shown
      to vary with dilution because of the combination of changes in partitioning
      coupled with adsorption of gas-phase organics by quartz filters. The fine
      particle mass emissions from the diesel engine operating at medium load did not
      vary with dilution because of the lower emissions of semivolatile material and
      higher emissions of elemental carbon. To measure partitioning of semivolatile
      materials under atmospheric conditions, partitioning theory indicates that
      dilution samplers need to be operated such that the diluted exhaust achieves
      atmospheric levels of dilution. Too little dilution can potentially overestimate
      the fine particle mass emissions, and too much dilution (with clean air) can
      underestimate them.

PMID- 16433347
TI  - Distributions of PM2.5 source strengths for cooking from the Research Triangle
      Park particulate matter panel study.
AB  - Emission rates, decay rates, and cooking durations are reported from continuous
      PM2.5 (particulate matter less than 2.5 microm) concentrations measured using
      personal DataRam nephelometers (1-min time resolution) from the Research Triangle
      Park (RTP) PM panel study. The study (n = 37 participants) included monitoring
      for 7 consecutive days in each of four consecutive seasons (summer 2000 through
      spring 2001). Cooking episodes (n = 411) were selected using time-activity
      diaries and criteria for cooking event duration, peak concentration level, and
      decay curve quality. Averaged across all cooking events, mean source strengths
      were 36 mg/min (median = 12 mg/min), mean decay rates were 0.27 h(-1) (0.17 h(
      1)), and mean cooking durations were 11 min (7 min). Cooking events were further
      separated into one of seven categories representing cooking method: burned food
      (oven cooking, toaster, or stovetop cooking), grilling, microwave, toaster oven,
      frying, oven cooking, and stovetop cooking. The highest mean source strengths
      were identified from burned food (mean = 470 mg/min), grilling (173 mg/min), and
      frying (60 mg/ min); differences between both burned food and grilling compared
      with all remaining cooking methods were statistically significant. Source
      strengths, decay rates, and cooking durations were also compared by season and
      typical meal times (8:00 a.m., 12:00 p.m., and 6:00 p.m.); differences were
      generally not statistically significant for these cases. Mean source strengths
      using electric appliances were typically a factor of 2 greater than those using
      gas appliances for identical cooking methods (frying, oven cooking, or stovetop
      cooking), although in all cases the difference was not statistically significant.
      Distributions of source strengths and decay rates for cooking events were also
      compared among study subjects to assess both within- and between-subject
      variability. Each subject's distribution of source strengths during the study
      tended to be either lower than the overall study average (and with lower
      variability) or higher than the overall study average (and with higher
      variability). No relationships could be found between source strength and either
      subject characteristics (age, gender, employment status) or home characteristic
      (daily air exchange rate). The large number of cooking events and the broad range
      of cooking activities included in this analysis makes the reported distributions
      of PM2.5 source strengths useful for probabilistic exposure modeling even though
      the study population was limited.

PMID- 16433348
TI  - Conditioning-annealing studies of natural organic matter solids linking
      irreversible sorption to irreversible structural expansion.
AB  - The assumption of reversibility underpins the sorption term in current models
      dealing with the fate and impact of organic compounds in the environment, yet
      experimentally sorption of organic compounds in soils and sediments often shows
      "irreversible" behaviors such as hysteresis and the conditioning effect (enhanced
      repeat sorption). The objective of this study was to test whether a glassy
      polymer irreversibility model applies to natural organic matter (NOM) solids.
      Irreversible sorption in polymers is believed to be caused by irreversible
      expansion and creation of internal micropores by penetrating molecules, leading
      to enhanced affinity during desorption or subsequent resorption. Using
      chlorobenzene as a conditioning agent and polychlorinated benzenes as test
      compounds in a second sorption step, we observed conditioning effects for a peat
      soil, a soil humic acid, and a model glassy polymer, poly- (vinyl chloride), but
      not for a model rubbery polymer, poly- (ethylene). The conditioning effect for
      the two natural solids, probed bythe enhancement in the sorption distribution
      coefficient of 1,2,4-trichlorobenzene, relaxed upon sample annealing between 45
      and 91 degrees C in a manner similar to the relaxation of free volume and
      enthalpy of glassy polymers. Relaxation of the conditioning effect in the NOM
      solids depended on annealing temperature and, at a given temperature, followed a
      double additive exponential rate law with a nonzero constant term descriptive of
      the final state that depends inversely on temperature. At environmentally
      relevant temperatures, the conditioning effect may "never" completely relax. The
      results provide compelling evidence for the glassy, nonequilibrium nature of
      natural organic matter solids and for irreversible structural expansion as a
      cause of irreversible sorption.

PMID- 16433349
TI  - Laboratory measurements of thermodynamics of adsorption of small aromatic gases
      to n-hexane soot surfaces.
AB  - The adsorption isotherms of a series of aromatic hydrocarbons on n-hexane soot
      were measured as a function of temperature and partial pressure in a coated-wall
      flow tube coupled to an electron-impact mass spectrometer. The specific surface
      area was determined for each of the samples by measuring the BET isotherm of Kr
      at 77 K. The gas-to-surface uptakes were fully reversible with the extent of
      adsorption increasing with decreasing temperature and increasing partial
      pressures. At low partial pressures, the isotherms were well modeled by the
      Langmuir isotherm for all experimental conditions, and the adsorption was found
      to saturate at one monolayer of coverage at approximately 2 x 10(14) molecule cm(
      2). For the less volatile species, evidence for multilayer adsorption was
      observed and the BET isotherm was used instead. The experimental enthalpies of
      adsorption were consistently higher than the enthalpies of vaporization for all
      compounds. A linear free-energy relationship was developed between the Langmuir
      equilibrium constant for adsorption and the compound's (sub-cooled) liquid vapor
      pressure, providing validation for the use of such relationships in assessing gas
      particle partitioning of aromatic hydrocarbons to soot aerosols in the
      environment. The experimental results were compared to the Junge-Pankow gas-to
      aerosol partitioning model.

PMID- 16433350
TI  - Impact of humidity on the ozone initiated oxidation of limonene, delta3-carene,
      and alpha-pinene.
AB  - The effect of water on the initial secondary organic aerosol (SOA) formation from
      gas-phase ozonolysis of limonene, delta3-carene, and alpha-pinene (-3 and
      approximately 1.5 x 10(11) molecule cm(-3) reacted) has been investigated in a
      flow reactor at controlled relative humidity (RH), temperature (298 +/- 0.4 K),
      and reaction time (270 +/- 2 s). Low amounts of terpene converted minimize the
      impact of secondary reactions. A comparison of the SOA formation from the three
      terpenes was made for initial rate of reactions being around 7.5 x 10(8) and 15 x
      10(8) molecule cm(-3) s(-1). The most efficient species in producing SOA was
      limonene, while alpha-pinene was the least efficient. The results showed that an
      enhancement in water vapor concentration (<2-85% RH) caused an increase in both
      integrated mass (M10-300nm) and total number (N10-300nm). The effect on number
      and mass were a factor of 2-3 and 4-8, respectively. Physical water up-take can
      partly explain the increase in mass, but not the observed increase in number.
      Therefore it was concluded that the increase in water concentration must, by a
      gas-phase reaction, produce more low volatility product(s).

PMID- 16433351
TI  - Effects of nonionic surfactants on the cell surface hydrophobicity and apparent
      hamaker constant of a Sphingomonas sp.
AB  - Nonionic surfactants of the form CxEy were studied for their ability to alter the
      cell surface hydrophobicity and apparent Hamaker constants of a Sphingomonas sp.
      Through contact angle measurements on hydrated and dried bacterial lawns, it was
      found that the cell surface hydrophobicity changed systematically with both the
      alkyl (x) and polyoxyethylene (y) chain lengths. While differences in contact
      angles were observed between hydrated and dried lawns, they could not be
      attributed to the mere presence or absence of water, suggesting that
      reorientation of cell surface components may occur during drying. All surfactants
      examined reduced the hydrophilicity of the bacterial cell surface, with one
      surfactant (C18E10) making the cells hydrophobic. Effective bacterial Hamaker
      constants for bacteria interacting across a vacuum (Abb) and water (Abwb) and
      bacteria interacting in water with quartz sand (Abws) were calculated from the
      contact angles. It was found that the surfactants have the potential to reduce
      the Hamaker constants, but that the overall effects differed between dried and
      hydrated lawns, indicating that lawn preparation method can have a significant
      impact in interpretation of cell surface properties. The results also indicate
      that the Abws value of 10-20 J, which is often assumed in bacterial attachment
      and transport studies, may be an order of magnitude higher than the actual value.
      Finally, the results suggest that alteration of bacterial adhesion due to the
      presence of surfactants cannot be attributed to a single cell surface property
      but is rather due to multiple interactions.

PMID- 16433352
TI  - Dimethyl sulfoxide (DMSO) waste residues and municipal waste water odor by
      dimethyl sulfide (DMS): the north-east WPCP plant of Philadelphia.
AB  - This study shows for the first time that overlooked mg/L concentrations of
      industrial dimethyl sulfoxide (DMSO) waste residues in sewage can cause "rotten
      cabbage" odor problems bydimethyl sulfide (DMS) in conventional municipal
      wastewater treatment. In laboratory studies, incubation of activated sludge with
      1-10 mg/L DMSO in bottles produced dimethyl sulfide (DMS) at concentrations that
      exceeded the odor threshold by approximately 4 orders of magnitude in the
      headspace gas. Aeration at a rate of 6 m3 air/m3 sludge resulted in emission of
      the DMS into the exhaust air in a manner analogous to that of an activated sludge
      aeration tank. A field study atthe NEWPCP sewage treatment plant in Philadelphia
      found DMSO levels intermittently peaking as high as 2400 mg/L in sewage near an
      industrial discharger. After 3 h, the DMSO concentration in the influent to the
      aeration tank rose from a baseline level of less than 0.01 mg/L to a level of 5.6
      mg/L and the DMS concentration in the mixed liquor rose from less than 0.01 to
      0.2 mg/L. Finding this link between the intermittent occurrence of DMSO residues
      in influent of the treatment plant and the odorant DMS in the aeration tank was
      the keyto understanding and eliminating the intermittent "canned corn" or "rotten
      cabbage" odor emissions from the aeration tank that had randomly plagued this
      plant and its city neighborhood for two decades. Sewage authorities should
      consider having wastewater samples analyzed for DMSO and DMS to check for this
      possible odor problem and to determine whether DMSO emission thresholds should be
      established to limit odor generation at sewage treatment plants.

PMID- 16433353
TI  - Micellar partitioning and its effects on Henry's law constants of chlorinated
      solvents in anionic and nonionic surfactant solutions.
AB  - Micellar partitioning of volatile chlorinated hydrocarbons in surfactant
      solutions and its effects on vapor-liquid equilibrium is fundamental to the
      overall design and implementation of surfactant-enhanced aquifer remediation.
      Surfactant micelles greatly enhance contaminant recovery from the subsurface;
      however, the reduced volatility of organic compounds compromises the aboveground
      treatment of surfactant-laden wastewaters using air-stripping process. Batch
      equilibrium tests were performed to acquire micellar partition coefficients (Km)
      and apparent Henry's law constants (H*) of three prominent groundwater
      contaminants (tetrachloroethylene, trichloroethylene, cis-dichlorethylene) in the
      presence of two anionic surfactants (sodium dodecyl sulfate, SDS; sodium
      dodecylbenzene sulfonate, SDBS) and two nonionic surfactants (Triton X-100 and
      Tween 80). The H* values were significantly reduced in the presence of all four
      surfactants over their critical micelle concentrations (cmc's). On a cmc basis,
      the anionic surfactant SDS had the greatest effect on H*, followed by SDBS,
      Triton X-100, and Tween 80. Anionic surfactants decreased H* to an order of
      magnitude lower than nonionic surfactants, although nonionic surfactants
      decreased the H* at concentrations significantly lower than the anionic
      surfactants due to their lower cmc's. Nonionic surfactants present higher Km and
      molar solubilization ratio than anionic surfactants. Tetrachloroethylene has the
      highest Km values among three chlorinated solvents, which agrees well with the
      hydrophobicity (Kow) of these chemicals. An empirical correlation between log Km
      and log Kow is developed on the basis of data from this study and the Km values
      reported for a number of chlorinated and nonchlorinated hydrocarbons. Equilibrium
      data were also tested against three sets of models that describe the partitioning
      of volatile compounds in vapor-water-micelle phases. Applications of these models
      in experimentally determining Km from batch vapor-water equilibrium data are
      discussed.

PMID- 16433354
TI  - Photodegradation of decabromodiphenyl ether adsorbed onto clay minerals, metal
      oxides, and sediment.
AB  - The photodebromination of decabromodiphenyl ether (BDE-209) adsorbed onto six
      different solid matrixes was investigated in sunlight and by irradiation with 350
      +/- 50 nm lamps (four lamps at 24 W each). After 14 days of lamp irradiation, BDE
      209 degraded with a half-life of 36 and 44 days, respectively, on montmorillonite
      or kaolinite, with much slower degradation occurring when sorbed on organic
      carbon-rich natural sediment (t1/2 = 150 days). In late summer and fall sunlight
      (40.5 degrees N, elevation 600 ft), the half-lives of BDE-209 sorbed on
      montmorillonite and kaolinite were 261 and 408 days, respectively. Under both
      irradiation schemes, no significant loss of BDE-209 occurred when sorbed to
      aluminum hydroxide, iron oxide (ferrihydrite), or manganese dioxide (birnessite).
      Upon exposure to both lamp and solar light and in the presence of montmorillonite
      and kaolinite, numerous lesser brominated congeners (tri- to nonabromodiphenyl
      ethers) were produced. Nearly identical product distribution was evident on
      montmorillonite and kaolinite. Dark control experiments for each mineral showed
      no disappearance of BDE-209 or appearance of degradation products. These results
      suggest that photodegradation of BDE-209 on mineral aerosols during long-range
      atmospheric transport may be an important fate process for BDE-209 in the
      environment.

PMID- 16433356
TI  - Electrochemical and XAFS studies of effects of carbonate on the oxidation of
      arsenite.
AB  - Measurements of electrochemical (EC) arsenite oxidation demonstrated thatthe
      arsenite oxidation current increased in the presence of carbonate while the
      potential of the onset of EC arsenite oxidation exhibited a strong shift toward
      less positive values. Examination of pH and total carbonate concentration effects
      on the EC arsenite oxidation parameters showed that they were affected solely by
      the concentration of carbonate ion CO3(2-), which appeared to form relatively
      weak mono- and dicarbonate complexes with arsenite. The EC activity of these
      complexes was determined to be almost an order of magnitude higher than that of
      free arsenite. However, X-ray absorption fine-structure (XAFS) measurements did
      not show any changes in the properties of the As(III) inner complexation shell
      associated with the presence of the bound carbonate ions. It was accordingly
      concluded that the strength of bonds between the bound carbonate and As(III) is
      close to that for As(III)-OH- interactions. The acceleration of the oxidation of
      carbonate-As(III) complexes was hypothesized to be associated with an additional
      pathway of the formation of As(IV) intermediates, in which the carbonate group
      present in the As(III) inner shell provides an electron to form a bound carbonate
      radical and also a good leaving group for facile cleavage from the transient
      As(IV) species.

PMID- 16433355
TI  - Effects of dissolved carboxylates and carbonates on the adsorption properties of
      thiuram disulfate pesticides.
AB  - The adsorption of thiram and disulfiram onto alpha-Al2O3 and montmorillonite clay
      has been studied in the presence of small carboxylate anions, bicarbonate,
      formate, and oxalate. At natural concentrations, HCO3- enhances dramatically the
      adsorption of both pesticides on alpha-Al2O3 and clay. An analogous significant
      enhancement of pesticide adsorption is also observed in the presence of formate
      and oxalate. Density functional theory calculations demonstrate that in solution
      a stable molecular complex between one molecule of thiram and one molecule of
      HCO3- is formed with interaction energy -35.6 kcal/mol. In addition, two H20
      molecules further stabilize it by an interaction energy of -3.6 kcal/mol. This
      clustering [thiram- HCO3- -2H2O] leads to a change of the electronic structure
      and the ultraviolet-visible spectrum of thiram that is observed experimentally.
      Surface complexation modeling shows that the molecular cluster [thiram-HCO3- 
      2H2O], which bears a total net charge of -1, is responsible for the observed
      enhanced adsorption on the charged surface of alumina and clay at pH below their
      points of zero surface charge. The results reveal a novel pervasive role of
      carboxylate anions and particularly HCO3- on the adsorption of dithiocarbamate
      pesticides in natural waters.

PMID- 16433357
TI  - Reduction of nitroaromatic compounds by Fe(II) species associated with iron-rich
      smectites.
AB  - Reductive transformation reactions involving mineral-bound Fe2+ species are of
      great relevance for the fate of groundwater contaminants. For clay minerals,
      which are ubiquitously present in soils and sediments, the factors determining
      the reactivity of structural Fe2+ and surface-bound Fe2+ are not well understood.
      We investigated the reactivity and availability of Fe2+ species in suspensions of
      chemically reduced montmorillonite (SAz-1) as well as in suspensions of oxidized
      and reduced nontronite (SWa-1, ferruginous smectite) using two acetylnitrobenzene
      isomers as reactive probe compounds. The analyses of the reduction kinetics of
      the two nitroaromatic compounds (NACs) suggested that Fe2+ bound in the
      octahedral layer of reduced smectites is the predominant reductant and that
      electron transfer presumably occurs via basal siloxane planes. In contrast,
      reduction of NACs by Fe2+ associated with oxidized nontronite is orders of
      magnitude slower than reduction by octahedral Fe2+. Reductive transformation and
      reversible, nonreactive electron donor-acceptor (EDA) complexation of NACs at
      basal smectite surfaces occur simultaneously at reduced montmorillonite
      exhibiting low structural iron content. In contrast, EDA complexation was not
      observed in suspensions of reduced iron-rich nontronite. Due to the similar
      reduction rate constants measured for the two NACs, we propose that the (re)-
      generation of octahedral Fe2+ sites, e.g., by electron transfer and/or Fe
      rearrangement within the octahedral nontronite layers, partly limited the rate of
      contaminant transformation. Since iron in clay minerals is available for
      microbial reduction, our study suggests that octahedral Fe2+ can contribute to
      abiotic contaminant transformation in anoxic environments.

PMID- 16433358
TI  - Groundwater dynamics and arsenic mobilization in Bangladesh assessed using noble
      gases and tritium.
AB  - The contamination of groundwater by geogenic arsenic is the cause of major health
      problems in south and southeast Asia. Various hypotheses proposing that As is
      mobilized by the reduction of iron (oxy)hydroxides are now under discussion. One
      important and controversial question concerns the possibility that As
      contamination might be related to the extraction of groundwater for irrigation
      purposes. If As were mobilized by the inflow of re-infiltrating irrigation water
      rich in labile organic carbon, As-contaminated groundwater would have been
      recharged after the introduction of groundwater irrigation 20-40 years ago. We
      used environmental tracer data and conceptual groundwater flow and transport
      modeling to study the effects of groundwater pumping and to assess the role of
      reinfiltrated irrigation water in the mobilization of As. Both the tracer data
      and the model results suggest that pumping induces convergent groundwater flow to
      the depth of extraction and causes shallow, young groundwater to mix with deep,
      old groundwater. The As concentrations are greatest at a depth of 30 m where
      these two groundwater bodies come into contact and mix. There, within the mixing
      zone, groundwater age significantly exceeds 30 years, indicating that recharge of
      most of the contaminated water occurred before groundwater irrigation became
      established in Bangladesh. Hence, at least at our study site, the results call
      into question the validity of the hypothesis that re-infiltrated irrigation water
      is the direct cause of As mobilization; however, the tracer data suggest that, at
      our site, hydraulic changes due to groundwater extraction for irrigation might be
      related to the mobilization of As.

PMID- 16433359
TI  - Atmospheric chlorine chemistry in southeast Texas: impacts on ozone formation and
      control.
AB  - Recent evidence has demonstrated that chlorine radical chemistry can enhance
      tropospheric hydrocarbon oxidation and has the potential to enhance ozone
      formation in urban atmospheres. To assess these effects quantitatively, an August
      September 2000 photochemical episode in southeast Texas was simulated using the
      comprehensive air quality model, with extensions (CAMx). During this episode,
      ambient measurements of a unique marker of atmospheric chlorine chemistry, 1
      chloro-3-methyl-3butene-2-one (CMBO), were made and model performance was
      assessed by comparing modeled and observed CMBO mixing ratios. The model
      predicted ambient CMBO mixing ratios within the uncertainty limits associated
      with the emissions inventory, so the model was used to assess the impacts of
      chlorine chemistry on ozone formation. Based on the current emissions inventory,
      chlorine emissions have the potential to enhance 1-h-averaged ozone mixing ratios
      by 70 ppb, in very localized areas, during morning hours. Over wider areas, and
      at times of day when peak ozone concentrations are observed, the impacts of
      chlorine emissions on ozone concentrations are typically less than 10 ppb.
      Chlorine emissions also influenced changes in ozone concentrations due to
      hydrocarbon and NOx emission controls.

PMID- 16433360
TI  - Anion adsorption on oxide surfaces: inclusion of the water dipole in modeling the
      electrostatics of ligand exchange.
AB  - Adsorption of aqueous anions, such as sulfate, arsenite, and oxalate, to oxide
      surfaces is important in the retardation of toxic species in the environment, but
      predicting the surface speciation as a function of environmental parameters is a
      major challenge. Recent laboratory spectroscopic studies defining surface
      speciation must be integrated with surface complexation models. However, the
      latter have neglected the electrostatic work of desorption of water dipoles in
      treating anion adsorption by ligand exchange. Taking this effect into account
      permits close quantitative description of anion adsorption and the prediction of
      anion surface speciation as a function of pH, ionic strength, and surface
      coverage in agreement with spectroscopic results.

PMID- 16433361
TI  - Modeling of the polluting emissions from a cement production plant by partial
      least-squares, principal component regression, and artificial neural networks.
AB  - A Portland cement process was taken into consideration and monitored for one
      month with respect to polluting emissions, fuel and raw material physical
      chemical properties, and operative conditions. Soft models, based on linear
      (partial least-squares, PLS, and principal component regression, PCR) and
      nonlinear (artificial neural networks, ANNs) approaches, were employed to predict
      the polluting emissions. The predictive ability of the three regression methods
      was evaluated by means of the partition of the dataset by Kohonen self
      associative maps into both a training and a test set. Then, a "leave-more-out"
      approach, based on the use of a training set, a test set, and a production set,
      was adopted. The training set was used to build the models, the test set was used
      to select the number of latent variables or the neural network training endpoint,
      and the production set was used to produce genuine predictions. ANNs proved to be
      much more effective in prediction with respect to PLS and PCR and, at least in
      the case of SO2 and dust, provided a predictive ability comparable with the
      experimental estimated uncertainty of the response. This showed that it is
      possible to satisfactorily predict the two responses. Such a prediction will
      result in the prevention of environmental and legal problems connected to the
      polluting emissions.

PMID- 16433362
TI  - Statistical procedures for determination and verification of minimum reporting
      levels for drinking water methods.
AB  - The United States Environmental Protection Agency's Office of Ground Water and
      Drinking Water has developed a single-laboratory quantitation procedure: the
      lowest concentration minimum reporting level (LCMRL). The LCMRL is the lowest
      true concentration for which future recovery is predicted to fall, with high
      confidence (99%), between 50% and 150%. The procedure takes into account
      precision and accuracy. Multiple concentration replicates are processed through
      the entire analytical method and the data are plotted as measured sample
      concentration (y-axis) versus true concentration (x-axis). If the data support an
      assumption of constant variance over the concentration range, an ordinary least
      squares regression line is drawn; otherwise, a variance-weighted least-squares
      regression is used. Prediction interval lines of 99% confidence are drawn about
      the regression. At the points where the prediction interval lines intersect with
      data quality objective lines of 50% and 150% recovery, lines are dropped to the x
      axis. The higher of the two values is the LCMRL. The LCMRL procedure is flexible
      because the data quality objectives (50-150%) and the prediction interval
      confidence (99%) can be varied to suit program needs. The LCMRL determination is
      performed during method development only. A simpler procedure for verification of
      data quality objectives at a given minimum reporting level (MRL) is also
      presented. The verification procedure requires a single set of seven samples
      taken through the entire method procedure. If the calculated prediction interval
      is contained within data quality recovery limits (50-150%), the laboratory
      performance at the MRL is verified.

PMID- 16433364
TI  - Pilot-scale evaluation of the application of low pH-inducible polyphosphate
      accumulation to the biological removal of phosphate from wastewaters.
AB  - To investigate the possible biotechnological application of the phenomenon of low
      pH-inducible phosphate uptake and polyphosphate accumulation, previously reported
      using pure microbial cultures and under laboratory conditions, a 2000 L activated
      sludge pilot plant was constructed at a municipal sewage treatment works. When
      operated as a single-stage reactor this removed more than 60% of influent
      phosphate from primary settled sewage at a pH of 6.0, as opposed to approximately
      30% at the typical operational pH for the works of 7.0-7.3-yet without any
      deleterious effect on other treatment parameters. At these pH values the
      phosphorus content of the sludge was, respectively, 4.2% and 2.0%. At pH 6.0 some
      33.9% of sludge microbial cells were observed to contain polyphosphate
      inclusions; the corresponding value at pH 7.0 was 18.7%. Such a process may serve
      as a prototype for the development of alternative biological and chemical options
      for phosphate removal from wastewaters.

PMID- 16433363
TI  - Quantitative determination of fluorinated alkyl substances by large-volume
      injection liquid chromatography tandem mass spectrometry-characterization of
      municipal wastewaters.
AB  - A quantitative method was developed for the determination of fluorinated alkyl
      substances in municipal wastewater influents and effluents. The method consisted
      of centrifugation followed by large-volume injection (500 microL) of the
      supernatant onto a liquid chromatograph with a reverse-phase column and detection
      by electrospray ionization and tandem mass spectrometry. The fluorinated analytes
      studied include perfluoroalkyl sulfonates, fluorotelomer sulfonates,
      perfluorocarboxylates, and select fluorinated alkyl sulfonamides. Recoveries of
      the fluorinated analytes from wastewater treatment plant (WWTP) raw influents and
      final effluent were in the ranges of 82-100% and 86-100%, respectively. The lower
      limit of quantitation was 0.5 ng/L depending on the analyte. The method was
      applied to flow-proportional composites of raw influent and final effluent
      collected over a 24 h period from 10 WWTPs nationwide. Fluorinated alkyl
      substances were observed in wastewater at all treatment plants, and each plant
      exhibited unique distributions of fluorinated alkyl substances despite
      similarities in treatment processes. In 9 out of the 10 plants sampled, at least
      one class of fluorinated alkyl substances exhibited increased concentrations in
      the effluent as compared to the influent concentrations. In some instances,
      decreases in certain fluorinated analyte concentrations were observed and
      attributed to sorption to sludge.

PMID- 16433365
TI  - Dried sludges and sludge-based chars for H2S removal at low temperature:
      influence of sewage sludge characteristics.
AB  - The use of sewage sludge as a precursor of adsorbent/ catalyst materials for
      environmental applications has been encouraged during the past few years. Due to
      the heterogeneous nature of sludges, there exists a lack of information regarding
      the characteristics of these low-cost precursors and how their physicochemical
      properties affect the final performance of materials prepared from them. In this
      work, three sewage-sludges collected at WWTPs with assorted sludge/wastewater
      treatment schemes were used as precursors of adsorbents/catalysts for H2S removal
      at room temperature. All the solidswere characterized to establish their textural
      properties and chemical composition, including the speciation of the adsorbents/
      catalysts inorganic fraction. Thermal treatment (gasification) of the raw (dried)
      sludges increased the H2S removal ability in all cases. For these thermally
      treated materials, catalytic conversion to elemental sulfur and sulfate moieties
      was found to be the main route of H2S removal. Results indicate that adsorbents
      based on an iron/calcium-containing sludge were the most reactive and exhibited
      the highest capacities for H2S retention. Forthis particulartype of sludge, a
      reasonably good performance was observed even when the dried (raw) sludge was
      used as adsorbent/ catalyst. Alternatively, the oxidation of H2S by chars
      obtained from the other two sludges under study was related to their textural
      properties.

PMID- 16433366
TI  - Stimulation and molecular characterization of bacterial perchlorate degradation
      by plant-produced electron donors.
AB  - Root homogenate from poplar trees (Populus deltoides x nigra DN34, Imperial
      Carolina) stimulated perchlorate degradation in microcosms of soil and water
      samples collected at a perchlorate contaminated site, the Longhorn Army
      Ammunition Plant (LHAAP), located outside Karnack, Texas. Direct use of root
      products by perchlorate-degrading bacteria was shown for the first time as six
      pureculture bacteria isolated from LHAAP perchlorate-degrading microcosms
      degraded perchlorate when given root products as the sole exogenous source of
      carbon and electron donor. Nonenriched environmental consortia were able to
      utilize root products for perchlorate degradation, regardless of prior exposure
      to perchlorate. Microcosms that contained perchlorate-contaminated groundwater
      (MW-3) or uncontaminated surface water (Harrison Bayou) as inoculum degraded
      approximately 240 and 160 mg L(-1) perchlorate, respectively, using root products
      (approximately 440 mg L(-1) as COD) over 38 days. The predominant bacterial
      species in these aqueous microcosms, identified by DGGE, depended only upon the
      source inoculum as similar sequences were obtained whether root products or
      lactate was the electron donor. Sequences from DGGE bands that matched species
      within Dechloromonas, a genus consisting of many perchlorate degraders, were
      identified in all perchlorate-degrading microcosms. This study demonstrates the
      ability of root products to drive perchlorate respiration by bacteria and the
      potential for successful achievement of perchlorate rhizodegradation using in
      situ phytoremediation.

PMID- 16433367
TI  - Biodegradability of 14C-labeled antibiotics in a modified laboratory scale sewage
      treatment plant at environmentally relevant concentrations.
AB  - For all new pharmaceuticals, an environmental risk assessment (ERA) has to be
      performed according to guidelines developed by the European Medicines Evaluation
      Agency. An important factor of this procedure is the assessment of the predicted
      environmental concentration in the aquatic environment, which is significantly
      influenced by the biodegradability of pharmaceuticals in sewage treatment plants.
      Established standardized methods for determining biodegradation under laboratory
      conditions apply to substance concentrations, which are much higherthan those
      expected in reality. Against this background, the laboratory scale sewage
      treatment plant (LSSTP), as described by the Organisation for Economic
      Cooperation and Development (OECD) Guideline No. 303A, was modified to construct
      a lossless system, which allows laboratory testing at realistic concentrations.
      To verify the experimental setup, the antibiotics benzylpenicillin, ceftriaxone,
      and trimethoprim were tested at low concentrations (microg/L) using 14C-labeled
      compounds. The results show that approximately 25% of benzylpenicillin was
      mineralized, whereas ceftriaxone and trimethoprim were not mineralized at all.
      Due to the high total recoveries of added radioactivity (> or =95%) and the fact
      that the findings comply with available literature data, the lossless operation
      of the test system could be proved. Consequently, the modified LSSTP is a
      suitable tool to determine more realistic biodegradation data required for the
      exposure assessment within the scope of an ERA for pharmaceuticals.

PMID- 16433368
TI  - Coagulation behavior of aluminum salts in eutrophic water: significance of Al13
      species and pH control.
AB  - The coagulation behavior of aluminum salts in a eutrophic source water was
      investigated from the viewpoint of Al(III) hydrolysis species transformation.
      Particular emphasis was paid to the coagulation effect of Al13 species on
      removing particles and organic matter. The coagulation behavior of Al coagulants
      with different basicities was examined through jar tests and hydrolyzed Al(III)
      speciation distribution characterization in the coagulation process. The results
      showed that the coagulation efficiency of Al coagulants positively correlated
      with the content of Al13 in the coagulation process ratherthan in the initial
      coagulants. Aluminum chloride (AICl3) was more effective than polyaluminum
      chloride (PACI) in removing turbidity and dissolved organic matter in eutrophic
      water because AlCl3 could not only generate Al13 species but also function as a
      pH control agent in the coagulation process. The solidstate 27Al NMR spectra
      revealed that the precipitates formed from AlCl3 and PACl were significantly
      different and proved that the preformed Al13 polymer was more stable than the in
      situ formed one during the coagulation process. Through regulating Al speciation,
      pH control could improve the coagulation process especially in DOC removal, and
      AlCl3 benefited most from pH control.

PMID- 16433369
TI  - Unregulated emissions from compressed natural gas (CNG) transit buses configured
      with and without oxidation catalyst.
AB  - The unregulated emissions from two in-use heavy-duty transit buses fueled by
      compressed natural gas (CNG) and equipped with oxidation catalyst (OxiCat)
      control were evaluated. We tested emissions from a transit bus powered by a 2001
      Cummins Westport C Gas Plus 8.3-L engine (CWest), which meets the California Air
      Resources Board's (CARB) 2002 optional NOx standard (2.0 g/bhp-hr). In
      California, this engine is certified only with an OxiCat, so our study did not
      include emissions testing without it. We also tested a 2000 New Flyer 40
      passenger low-floor bus powered by a Detroit Diesel series 50G engine (DDCs50G)
      that is currently certified in California without an OxiCat. The original
      equipment manufacturer (OEM) offers a "low-emission" package for this bus that
      includes an OxiCat for transit bus applications, thus, this configuration was
      also tested in this study. Previously, we reported that formaldehyde and other
      volatile organic emissions detected in the exhaust of the DDCs50G bus equipped
      with an OxiCat were significantly reduced relative to the same DDCs50G bus
      without OxiCat. In this paper, we examine othertoxic unregulated emissions of
      significance. The specific mutagenic activity of emission sample extracts was
      examined using the microsuspension assay. The total mutagenic activity of
      emissions (activity per mile) from the OxiCat-equipped DDC bus was generally
      lower than that from the DDC bus without the OxiCat. The CWest bus emission
      samples had mutagenic activity that was comparable to that of the OxiCat-equipped
      DDC bus. In general, polycyclic aromatic hydrocarbon (PAH) emissions were lower
      forthe OxiCat-equipped buses, with greater reductions observed for the volatile
      and semivolatile PAH emissions. Elemental carbon (EC) was detected in the exhaust
      from the all three bus configurations, and we found that the total carbon (TC)
      composition of particulate matter (PM) emissions was primarily organic carbon
      (OC). The amount of carbon emissions far exceeded the PM-associated inorganic
      element emissions, which were detected in all exhaust samples, at comparatively
      small emission rates. In summary, based on these results and those referenced
      from our group, the use of OxiCat for the new CWest engine and as a retrofit
      option for the DDCs50G engine generally results in the reduction of tailpipe
      toxic emissions. However, the conclusions of this study do not take into account
      OxiCat durability, deterioration, lubricant consumption, or vehicle maintenance,
      and these parameters merit further study.

PMID- 16433370
TI  - PCDD/F and other micropollutants in MSWI crude gas and ashes during plant start
      up and shut-down processes.
AB  - Nonstationary combustion conditions at municipal solid waste incineration (MSWI)
      plants cause increased crude gas concentrations of polychlorinated dibenzo-p
      dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and other products of
      incomplete combustion (PIC). Such transient conditions occur, e.g., during and
      after start-up processes in MSWI plants. The start-up and shut-down processes of
      a MSWI plant were investigated in detail. PCDD/F and other PIC concentrations
      were determined in the crude gas, in the boiler ash, and in the ash from the
      electrostatic precipitator (ESP ash), with the outcome that only the start-up
      procedure significantly affected the concentrations of the organic pollutants in
      the flue gas and in the ESP ash. The shut-down procedure was evaluated as less
      problematic for the concentration of the organic pollutants. Moreover the
      concentration of the PCDD/F and other PIC in the boiler ash was determined as not
      influenced by shut-down and start-up processes. The homologue profiles and the
      congener patterns as well as the PCDF/PCDD ratio in the flue gas and in the ESP
      ash change during MSWI start-up. The changing patterns point at a transition from
      dominant de novo synthesis to precursor synthesis.

PMID- 16433371
TI  - Competitive effects of natural organic matter: parametrization and verification
      of the three-component adsorption model COMPSORB.
AB  - Natural organic matter (NOM) hinders adsorption of trace organic compounds on
      powdered activated carbon (PAC) via two dominant mechanisms: direct site
      competition and pore blockage. COMPSORB, a three-component model that
      incorporates these two competitive mechanisms, was developed in a previous study
      to describe the removal of trace contaminants in continuous-flow hybrid PAC
      adsorption/membrane filtration systems. Synthetic solutions containing two model
      compounds as surrogates for NOM were used in the original study to elucidate
      competitive effects and to verify the model. In the present study, a quantitative
      method to characterize the components of NOM that are responsible for competitive
      adsorption effects in natural water was developed to extend the application of
      COMPSORB to natural water systems. Using batch adsorption data, NOM was
      differentiated into two fictive fractions, representing the strongly competing
      and pore blocking components, and each was treated as a single compound. The
      equilibrium and kinetic parameters for these fictive compounds were calculated
      using simplified adsorption models. This parametrization procedure was carried
      out on two different natural waters, and the model was verified with experimental
      data obtained for atrazine removal from natural water in a PAC/membrane system.
      The model predicted the system performance reasonably well and highlighted the
      importance of considering both direct site competition and pore blockage effects
      of NOM in modeling these systems.

PMID- 16433372
TI  - Removal of pharmaceuticals in sewage treatment plants in Italy.
AB  - A listing of "priority pharmaceuticals" for human use in Italy resulted in the
      selection of 26 pharmaceuticals, belonging to 11 therapeutic classes. They were
      analyzed by liquid chromatography-tandem mass spectrometry, their occurrence was
      assessed in six sewage treatment plants (STPs), and the loads and the removal
      rates (RR) were studied. Total loads ranged from 1.5 to 4.5 g/day/1000
      inhabitants in influents and 1.0 and 3.0 g/day/1000 inhabitants in effluents.
      Total RR in STPs were mostly lower than 40%. Pharmaceuticals could be divided
      into three groups according to their behavior in STPs: one group with RR higher
      in summer than in winter, one group with RR similar in summer and winter, and a
      last group not removed. Last, we studied the distribution and fate of residual
      pharmaceuticals in the surface waters receiving the effluents of the STPs and
      identified degradation and sorption as the major factors affecting attenuation.
      Ciprofloxacin, ofloxacin, sulfamethoxazole (antibiotics), atenolol
      (cardiovascular drug), ibuprofen (antiinflammatory), furosemide,
      hydrochlorothiazide (diuretics), ranitidine (gastrointestinal drug), and
      bezafibrate (lipid regulator) were the most abundant residual drugs, thus those
      of environmental concern.

PMID- 16433373
TI  - Power densities using different cathode catalysts (Pt and CoTMPP) and polymer
      binders (nafion and PTFE) in single chamber microbial fuel cells.
AB  - Cathode catalysts and binders were examined for their effect on power densities
      in single chamber, air-cathode, microbial fuel cells (MFCs). Chronopotentiometry
      tests indicated thatthe cathode potential was only slightly reduced (20-40 mV)
      when Pt loadings were decreased from 2 to 0.1 mg cm(-2), and that Nafion
      performed better as a Pt binder than poly(tetrafluoroethylene) (PTFE). Replacing
      the precious-metal Pt catalyst (0.5 mg cm(-2); Nafion binder) with a cobalt
      material (cobalt tetramethylphenylporphyrin, CoTMPP) produced slightly improved
      cathode performance above 0.6 mA cm(-2), but reduced performance (<40 mV) at
      lower current densities. MFC fed batch tests conducted for 35 cycles (31 days)
      using glucose showed that replacement of the Nafion binder used for the cathode
      catalyst (0.5 mg of Pt cm(-2)) with PTFE reduced the maximum power densities
      (from 400 +/- 10 to 480 +/- 20 mW m(-2) to 331 +/- 3 to 360 +/- 10 mW m(-2)).
      When the Pt loading on cathode was reduced to 0.1 mg cm(-2), the maximum power
      density of MFC was reduced on average by 19% (379 +/- 5 to 301 +/- 15 mW m(-2);
      Nafion binder). Power densities with CoTMPP were only 12% (369 +/- 8 mW m(-2))
      lower over 25 cycles than those obtained with Pt (0.5 mg cm(-2); Nafion binder).
      Power densities obtained using with catalysts on the cathodes were approximately
      4 times more than those obtained using a plain carbon electrode. These results
      demonstrate that cathodes used in MFCs can contain very little Pt, and that the
      Pt can even be replaced with a non-precious metal catalyst such as a CoTMPP with
      only slightly reduced performance.

PMID- 16433374
TI  - Environmentally benign hardness removal using ion-exchange fibers and snowmelt.
AB  - Many industrial unit operations and unit processes require near-complete removal
      of hardness to avoid scaling in heat-transfer equipment, fouling in membranes,
      and high consumption of detergents and sequestering chemicals in cooling and wash
      water. Lime softening and cation exchange are the most commonly used processes
      practiced to date for hardness removal. Herein, we report and discuss the results
      and attributes of a new hardness removal process using ion-exchange fibers (IX
      fibers). Most importantly, the process uses harvested snowmelt (or rainwater) as
      the regenerant chemical along with sparged carbon dioxide. Consequently, the
      spent regenerant does not contain a high concentration of aggressive chemicals
      such as sodium chloride or acid like traditional ion-exchange processes nor does
      the process produce voluminous sludges similar to lime softening. The bulk of
      carbon dioxide consumed during regeneration remains sequestered in the aqueous
      phase as alkalinity. IX-fibers form the heart of the process. They are
      essentially thin cylindrical polymeric strands 10-20 microm in diameter. The weak
      acid carboxylate functional groups reside near to the surface of these
      cylindrical fibers. Low intraparticle diffusional resistance is the underlying
      reason IX-fibers are amenable to efficient regeneration with snowmelt sparged
      with carbon dioxide. When the carbon dioxide partial pressure is increased to 6.8
      atm, over 90% calcium desorption efficiency is obtained. On the contrary,
      commercial weak-acid ion-exchange resins in spherical bead forms are ineffective
      for regeneration with carbon-dioxide-sparged snowmelt due to extremely slow ion
      exchange kinetics involving counter-transport of Ca2+ and H+.

PMID- 16433375
TI  - Evidence of altered gene flow, mutation rate, and genetic diversity in redbreast
      sunfish from a pulp-mill-contaminated river.
AB  - To determine effects of pulp mill effluent on population genetic structure,
      redbreast sunfish (Lepomis auritus) were collected from several sites along the
      Pigeon River, NC, as well as from reference sites. Previous studies found effects
      on molecular, biochemical, physiological, population, and community level
      endpoints in these populations. The population genetic structure of these fish
      was determined using the randomly amplified polymorphic DNA (RAPD) technique. The
      level of genetic diversity was higher in the Pigeon River populations than in the
      reference populations. Genetic distances among populations could not be explained
      by drainage patterns and may have been altered by contaminant exposure.
      Phylogeographic analysis, maximum likelihood analysis, and assignment tests
      suggested that there were fewer emigrants and more immigrants in the contaminated
      sites than in the reference sites, suggesting that the contaminated sites may
      harbor "sinklike" populations. Finally, a "terminal branch amplitype" analysis
      (neighbor-joining and minimum-spanning trees) and maximum likelihood analysis
      indicated that there may be an elevated mutation rate in the polluted sites.
      Thus, the genetic diversity (within and among populations) in the Pigeon River
      populations may have been affected by altered gene flow and mutational processes
      as a result of pulp mill effluent discharge.

PMID- 16433376
TI  - Internal exposure, health effects, and cancer risk of humans exposed to
      chloronitrobenzene.
AB  - Chloronitrobenzenes (CNBs) are important intermediates for the production of
      dyes, pesticides, rubber chemicals, and drugs. 2CNB and 4CNB are possible human
      carcinogens. Therefore, it is important to develop methods to biomonitor people
      exposed to these occupational and environmental pollutants. We developed a method
      to determine hemoglobin (Hb) adducts of CNBs. Nitrobenzenes and the resulting
      arylamines yield the same sulfinamide adducts. Therefore, after base hydrolysis
      of the isolated Hb the corresponding arylamines are released and quantified by GC
      MS. The method was applied to monitor 39 Chinese workers exposed to CNB and 15
      control workers from the same factory. The determined Hb adduct levels were
      compared to the measured air levels, the clinical blood and urine parameters, and
      health effects identified in the workers. The median Hb adduct levels resulting
      from exposure to 2CNB and 4CNB were 82.9 and 1013 pg/mg of Hb, respectively. The
      median air concentrations determined from personal samplers were 0.37 and 0.87
      mg/m3 for 2CNB and 4CNB, respectively. The air levels did not correlate with the
      Hb adduct levels. The median Hb adduct levels were higher in workers with
      fatigue, eye irritation, splenomegaly, and cardiovascular effects. Most negative
      urinary clinical parameters were present at higher median Hb adduct levels. The
      clinical blood parameters decreased at higher adduct levels. The daily dose was
      estimated from the Hb adduct levels and used to estimate the cancer risk.

PMID- 16433377
TI  - Bayesian and time-independent species sensitivity distributions for risk
      assessment of chemicals.
AB  - Species sensitivity distributions (SSDs) are increasingly used to analyze
      toxicity data but have been criticized for a lack of consistency in data inputs,
      lack of relevance to the real environment, and a lack of transparency in
      implementation. This paper shows how the Bayesian approach addresses concerns
      arising from frequentist SSD estimation. Bayesian methodologies are used to
      estimate SSDs and compare results obtained with time-dependent (LC50) and time
      independent (predicted no observed effect concentration) endpoints for the
      insecticide chlorpyrifos. Uncertainty in the estimation of each SSD is obtained
      either in the form of a pointwise percentile confidence interval computed by
      bootstrap regression or an associated credible interval. We demonstrate that
      uncertainty in SSD estimation can be reduced by applying a Bayesian approach that
      incorporates expert knowledge and that use of Bayesian methodology permits
      estimation of an SSD that is more robust to variations in data. The results
      suggest that even with sparse data sets theoretical criticisms of the SSD
      approach can be overcome.

PMID- 16433378
TI  - Chemical speciation and bioaccessibility of arsenic and chromium in chromated
      copper arsenate-treated wood and soils.
AB  - This research compares the As and Cr chemistry of dislodgeable residues from
      chromated copper arsenate (CCA)-treated wood collected by two different
      techniques (directly from the board surface either by rubbing with a soft bristle
      brush or by rinsing from human hands after contact with CCA-treated wood) and
      demonstrates that these materials are equivalent in terms of both the chemical
      form and bonding of As and Cr and in terms of the As leaching behavior. This
      finding links the extensive chemical characterization and bioavailability testing
      that has been done previously on the brush-removed residue to a material that is
      derived from human skin contact with CCA-treated wood. Additionally, this
      research characterizes the arsenic present in biological fluids (sweat and
      simulated gastric fluid) following contact with these residues. The data
      demonstrate that in biological fluids the arsenic is present primarily as free
      arsenate ions. Arsenic-containing soils were also extracted into human sweat to
      evaluate the potential for arsenic dissolution from soils at the skin surface.
      For soils from field sites, only a small fraction of the total arsenic is soluble
      in sweat. Based on comparisons to reference materials that have been used for in
      vivo dermal absorption studies, these findings suggest that the actual relative
      bioavailability via dermal absorption of As from CCA residues and soil may be
      well below the current default value of 3% used by U.S. EPA.

PMID- 16433379
TI  - Election year 2006: healthcare action at the state level.

PMID- 16433380
TI  - Unbundling the confusion about "unbundling" of charges.
AB  - Rejecting service codes on the basis that they have been unbundled has become a
      popular way for payers to reduce total billed charges. However, the contract
      between the hospital and the payer, and not Medicare or some hastily manufactured
      and inconsistent industry standard, controls the obligation to pay for healthcare
      services.

PMID- 16433381
TI  - New kid in town.
AB  - Hospitals can prepare for APC-based systems by: Paying close attention to the
      modifications that state payers make to Medicare's APC policies. Proactively
      monitoring and adjusting billing practices to be as consistent with the state
      payers' APC billing requirements as possible, even if the billing requirements
      have no effect on current payments for services. Analyzing the ways in which
      state payer APC policies vary from Medicare to anticipate the impact of these
      systems on their hospitals' operations and financial condition.

PMID- 16433382
TI  - Understanding your true cost to collect.

PMID- 16433383
TI  - Finance and nursing the business of caring.

PMID- 16433384
TI  - Telling the story of community benefit.
AB  - CFOs can enhance community benefit reporting by: Educating managers on what
      community benefit is, and how to document it. Generating excitement among staff
      about the community benefit that the organization provides, so that employees
      will be more likely to document examples of community benefit. Providing
      quarterly reminders to staff on the need to document community benefit.
      Simplifying the way in which managers record this information. Recognizing staff
      and physicians for exemplary commitment to community benefit initiatives

PMID- 16433385
TI  - Medicaid: facing the facts.
AB  - The key to making Medicaid more sustainable is to make it less necessary: By
      addressing coverage for the uninsured. By having Medicare offer more
      comprehensive coverage and long-term care assistance to its low-income
      beneficiaries. By providing an alternative to Medicaid's spend-down to
      impoverishment to gain assistance with long-term care costs.

PMID- 16433386
TI  - What's on your plate? Ten top issues for 2006.
AB  - Here, in order of importance, are the top 10 things to think about-and act on-in
      2006: Balancing clinical and financial issues, Getting ready for pay for
      performance, Implementing the electronic health record, Making your pricing
      transparent, Boosting your revenue cycle, Developing different ways to access
      capital, Increasing transparency in financial reporting, Getting your charity
      care policies and procedures in order, Improving leadership skills, Dealing with
      staffing shortages.

PMID- 16433387
TI  - What does it take to lead?

PMID- 16433388
TI  - Pharmacy cost reporting with an eye on the future.
AB  - The Centers for Medicare and Medicaid Services has decided not to pay hospitals a
      specific rate in 2006 to cover drug handling costs, but that doesn't mean it
      won't do so in the future. Hospitals that are dividing their reporting of
      pharmacy costs on Medicare cost reports between "Pharmacy" and "Drugs Charged to
      Patients" may be exemplifying best practice in accounting for such costs. Best
      practice hospitals will help ensure that CMS will set fair rates for drug
      handling payments to hospitals, in the event it decides such payments are
      appropriate.

PMID- 16433389
TI  - Innovative strategies for self-pay segmentation.
AB  - Risk segmentation of self-pay accounts can help healthcare financial managers
      determine where to use collection resources. Assessment of self-pay patients
      should consider each patient's estimated financial condition and potential
      eligibility for charity care of public assistance patients. Segmenting patients
      on the basis of demographic variances and potential fraud can help hospitals
      increase self-pay collections and reduce A/R days.

PMID- 16433390
TI  - Self test: are you an engaged leader?

PMID- 16433391
TI  - Expectations without accomplishment.

PMID- 16433392
TI  - Assessing the IT function in less than one day.
AB  - It's possible to gauge a hospital's IT functions in one day by hiring a
      consultant to review three key areas: infrastructure and application performance,
      execution, and alignment. To do so, the consultant should speak with: The
      hospital's CIO, Members of the IT department, Three senior members of the
      leadership team, A small sample of frontline managers, A sample of front-line
      users who were involved in recent implementations.

PMID- 16433393
TI  - Miniclinics: trend, threat, or opportunity?

PMID- 16433394
TI  - Alternatives: the right medicine for your portfolio?
AB  - Because they often play an active role in developing their portfolio companies'
      strategies, private capital investment managers can add significant value to
      companies in their portfolio. The relative inefficiency of private capital
      markets can give savvy investors an edge that they can not so easily gain in the
      more efficient public markets. Originally created as a means to reduce
      volatility, hedge funds should not be seen as the high-risk bets that they are
      widely perceived to be. Most hedge funds actually are concerned with protecting
      downside risk.

PMID- 16433395
TI  - Admissions and payments rise due to nontraditional Medicare patients.

PMID- 16433396
TI  - Restorative treatment of cervical lesions with resin composites: 4-year results.
AB  - PURPOSE: To verify the clinical behavior of two resin-based composites with
      different Young's modulus (AElite Fil and Elite Flo) in the restoration of
      carious and non-carious cervical lesions after 48 months of clinical service.
      METHODS: 116 restorations with the two different materials (60 with AElite Fil
      and 56 with AElite Flo) were performed in 15 patients and controlled for 48
      months. Retention rate and USPHS criteria were recorded at 6, 12, 24, 36 and 48
      months. RESULTS: The retention rate was 66% for AElite Fil in carious and non
      carious lesions and 65 and 47% for AElite Flo in carious and non-carious lesions
      respectively at 48 months. A decrease of quality of restorations in time was
      recorded with all USPHS criteria, with no statistically significant difference
      between materials tested.

PMID- 16433398
TI  - Durability of resin-dentin bonds related to water and oil storage.
AB  - PURPOSE: To evaluate the long-term effects of etching time, adhesive system and
      storage condition on resin bond strength to dentin. METHODS: Twenty-five
      extracted human third molars had a flat dentin surface exposed. Two total-etch
      adhesives, Single Bond (SB) and One-Step (OS), and one self-etching adhesive
      system, Clearfil Liner Bond 2V (CL), were used. The adhesives were bonded to
      dentin according to their respective manufacturer's instructions. Additional
      groups of SB and OS systems were created, in which the phosphoric acid etching
      time was doubled (30 seconds). After bonding, build-up crowns were constructed
      incrementally with Z250 resin composite and the teeth were stored for 24 hours in
      distilled water at 37 degrees C. The teeth were serially and vertically sectioned
      to obtain several bonded beams with approximately 0.8 mm2 of cross-sectional
      area. Beams were tested in microtensile (0.6 mm/minute) either immediately
      (control) or after storage for 6 months or 1 year in either distilled water or
      mineral oil. Data were analyzed by ANOVA and Tukey's multiple comparison tests.
      RESULTS: Significant reductions (P< 0.05) in bond strength were observed after
      both long-term storage periods in water for all the materials, regardless of the
      etching time for SB and OS. Bond strengths were either preserved or increased in
      specimens stored in oil.

PMID- 16433397
TI  - Effect of cavity form on adhesion to cavity floor.
AB  - PURPOSE: To investigate the influence of cavity form, namely the C-factor, on
      adhesion at the interface on the cavity floor using light-cured resin-based
      composite. METHODS: Black ABS resin molds were used and were formed into five
      types of cavities having configuration factors that ranged from 0.5 to 5.0. The
      cavity size was standardized to cubes of 5 x 5 x 5 mm. Each cavity was treated
      using a bonding system (Clearfil SE Bond) and was filled with resin-based
      composite (Clearfil Photo Core). The composite was irradiated in the cavity and
      then cured for 40 seconds using a halogen light unit. Specimens were subjected to
      the microtensile test at a cross-head speed of 1 mm/minute. RESULTS: There was no
      significant difference in bond strength among the five different cavity forms. It
      was concluded that the difference of cavity forms had little effect on the
      adhesion to the cavity floor when using light-cured composites.

PMID- 16433400
TI  - Adhesion promoters: effects on the bond strength of brackets.
AB  - PURPOSE: To evaluate the effect of two adhesion promoters on shear bond strength
      and remnant adhesive of brackets cemented with a light-cured orthodontic adhesive
      resin system. METHODS: The two adhesion promoters tested were OrthoSolo and All
      Bond 2 Primer. Seventy-five upper premolars were divided into three groups of 25.
      A control group was established using Transbond-XT adhesive system and two
      experimental groups: Transbond-XT/OrthoSolo and Transbond-XT/All-Bond 2. Shear
      bond strength was measured using a universal testing machine and adhesive remnant
      was quantified using an image analysis equipment. RESULTS: The application of
      Orthosolo significantly increased bond strength for Transbond-XT adhesive system
      (P< 0.017). All-Bond 2 primer did not significantly increase the bond strength of
      Transbond-XT (P> 0.017). The Adhesive Remnant Index results and the analysis of
      the percentage of area of tooth occupied by adhesive indicated that adhesive
      remnant after debonding did not increase significantly (P> 0.05) with the use of
      either of the promoters.

PMID- 16433399
TI  - Effect of adhesive volume on the bond strength of bonded complex amalgam
      restorations.
AB  - PURPOSE: To evaluate in vitro the effect of adhesive volume on the bond strength
      of bonded complex amalgam restorations using Amalgambond Plus with HPA powder.
      METHODS: Standardized 6 mm-diameter dentin cylinders were prepared from 30
      extracted human molar teeth. Specimens were divided into two groups (n=15). Group
      1 received a minimal volume (5 microl) of Amalgambond Plus with HPA powder and
      Group 2 received a surplus volume (10 microl) of Amalgambond Plus with HPA
      powder. Amalgam restorations were placed, and loaded at 45 degrees to the long
      axis of the tooth using an Instron testing machine. RESULTS: Group 1: 14.71 (+/-
      3.41) MPa, Group 2: 15.67 (+/- 3.72) MPa. A Student's t-test indicated no
      significant difference between the groups (P> 0.05).

PMID- 16433401
TI  - Tensile bond strength of self-etching adhesive systems to primary dentin.
AB  - PURPOSE: To assess in vitro the bond strength of three self-etching adhesive
      systems to primary teeth dentin. METHODS: Fifteen crowns of primary molars were
      sectioned mesiodistally and embedded in acrylic resin (n=30). Dentin was exposed
      and the specimens were randomly assigned in groups (n=10): (1) Clearfil SE Bond;
      (2) Prime & Bond NT/NRC; and (3) One Up Bond F. A 3 mm-diameter dentin bonding
      site was demarcated, the adhesive systems were applied and resin composite cones
      were bonded. After 24 hours in distilled water, tensile bond strength was tested
      to failure (0.5 mm/minute). Data were submitted to statistical analysis using one
      way ANOVA and Scheffe test. RESULTS: Means were (MPa): (1) 16.60 (+/- 4.10); (2)
      8.48 (+/- 4.51); and (3) 6.75 (+/- 1.26). CSE Bond yielded significantly higher
      bond strengths (P < 0.05). Prime & Bond NT/NRC and One Up Bond F means were
      markedly low and no statistically significant difference was observed between
      them.

PMID- 16433402
TI  - Micro-shear bond strength of five resin-based composites to dentin with five
      different dentin adhesives.
AB  - PURPOSE: To test whether the combination of dentin adhesive and resin-based
      composite from the same manufacturer had higher micro-shear bond strength than
      the other combinations of different manufacturers. METHODS: 25 experimental micro
      shear bond test groups were made from the combination of five resin-based
      composites and five dentin adhesives (three total-etch adhesives and two self
      etch adhesives) with extracted human molars stored in saline for 24 hours. The
      test was performed with the wire-loop method using a universal testing machine,
      and the micro-shear bond strengths were calculated. SEM photomicrographs of
      fractured sites were taken to check the failure mode. RESULTS: The combinations
      from same manufacturers failed to show higher bond strengths than the other
      combinations. Self-etch adhesives showed significantly higher micro-shear bond
      strengths than total-etch adhesives (P < 0.05). In total-etch adhesives, the kind
      of resin composite was important and in self-etch adhesives, the kind of adhesive
      had significant effect on micro-shear bond strength (P < 0.05). All sites showed
      mixed fractures.

PMID- 16433403
TI  - Effect of different mouthrinses on Knoop hardness of a restorative composite.
AB  - PURPOSE: To evaluate the effect of mouthrinses on Knoop hardness number (KHN) of
      a restorative composite, at different exposure times. METHODS: 50 composite
      specimens (TPH Spectrum) were randomly allocated into five groups (n=10):
      distilled water; Listerine; Reach; Plax and Periogard. The samples were immersed
      daily for 14 days in 20 ml of the respective solution for 2 minutes twice a day
      (with a 12-hour interval between exposures). Measurements were carried out at
      four different times: 1 hour after sample preparation, 1, 7 and 14 days after the
      first immersion in the solutions. RESULTS: Statistical analyses (Repeated
      Measures ANOVA and Tukey test at 0.05 significance level) showed significant
      differences among KHN of t wo experimental groups (mean values): Listerine
      (49.17) and Plax (51.14). There was n ointeraction between products and time,
      although the highest means were registered 24 hours after the first immersion for
      all tested groups.

PMID- 16433404
TI  - Subgingival topical doxycycline versus mechanical debridement for supportive
      periodontal therapy: a single blind randomized controlled two-center study.
AB  - PURPOSE: To evaluate the clinical effects of topical subgingival application of a
      doxycycline gel compared to conventional mechanical debridement in supportive
      periodontal therapy. METHODS: 37 patients with residual or recurring
      periodontitis after systematic periodontal treatment at two centers (Heidelberg,
      Frankfurt) participated in this study. They had to exhibit at least one single
      rooted tooth with either a probing depth (PPD) = 5 mm and bleeding-on-probing
      (BOP) or with PPD > or = 6 mm. The patients were randomly assigned to one of the
      two different treatment regimes: DOXY (exclusively subgingival application of a
      14% doxycycline gel) or SRP (scaling and root planing with a sonic scaler).
      Clinical examinations (plaque index [P1I], PPD, vertical relative attachment
      level [RAL-V], gingival index [GI]) were performed before, 3, and 6 months after
      therapy. RESULTS: In 37 patients (19 female), aged 30-76 years with a total of
      168 teeth were treated (DOXY: 79; SRP: 89). Six months after therapy, both groups
      exhibited statistically significant (P< 0.001) reductions of PPD (DOXY: -1.43 +/-
      0.22 mm; SRP: -1.14 +/- 0.18 mm) and gains of RAL-V (DOXY: 0.79 +/- 0.22 mm; SRP:
      0.72 +/- 0.19 mm). Multilevel regression analyses, considering the therapy of
      different numbers of teeth in different patients, failed to show statistically
      significant differences concerning PPD reduction and RAL-V gain between both
      therapies (DOXY/SRP). For both therapies, PPD reduction was significantly better
      in deeper pockets (PPD > or = 7 mm) than in shallow pockets (PPD: 5-6 mm).

PMID- 16433405
TI  - Evaluation of various root canal filling materials in primary molar pulpectomies:
      an in vivo study.
AB  - PURPOSE: To evaluate the clinical and radiographic success of zinc oxide-eugenol
      (ZOE), Calcicur, Sealapex and Vitapex in primary molar pulpectomies. METHODS: 80
      primary molars, showing signs of pulpal and/or periapical involvement, with no
      abnormal mobility, were selected from 76 children aged between 4-9 years-old,
      free from systemic disease. Radiographic evaluation was done to exclude teeth
      showing internal or pathological external root resorption and/or inadequate bone
      support. The selected teeth (20 in each group) were randomly treated with ZOE,
      Sealapex, Calcicur and Vitapex. The procedure involved primarily a one-visit
      pulpectomy. The teeth were evaluated clinically and radiographically every 2
      months for a period of 18 months. RESULTS: In the ZOE group, all pulpectomies
      were successful. In the Sealapex group, two pulpectomies and in the Calcicur
      group, four pulpectomies showed complete resorption of the material in the root
      canal. Although re-treatment was performed, those teeth had to be removed due to
      pathological root resorption. In the Vitapex group, although six pulpectomies
      showed resorption of the filling material within the canals, this had no effect
      on the clinical and radiographical success of the treatment.

PMID- 16433406
TI  - Evaluation of laser fluorescence for differentiating caries dye-stainable versus
      caries dye-unstainable dentin in carious lesions.
AB  - PURPOSE: To assess the performance of laser fluorescence (DIAGNOdent, "DD") for
      differentiating carious versus non-carious dentin during caries excavation using
      caries dye as the gold standard. METHODS: The superficial carious dentin surfaces
      of lesions in 25 teeth were exposed, and the surface evaluated by DD. Next,
      caries dye was applied and the surface was observed for dye staining. The lesion
      was then excavated approximately 0.5 mm with a round bur. The resulting surface
      was evaluated by DD, and the above sequence was repeated until three non-stained
      surfaces were evaluated by DD. Using "caries dye staining" as the gold standard,
      correct classification proportion was calculated at each DD cutpoint in the
      dataset. Using the optimal cutpoint, sensitivity, specificity and likelihood
      ratios were calculated. Non-parametric ROC analysis was performed and AUC
      calculated. RESULTS: With an optimal cutpoint of 11 or 12, DD was highly accurate
      in discriminating between dye-stainable and dye-unstainable surfaces, producing a
      correct classification proportion of over 98% and an AUC of 0.999 for all 176
      surfaces. These results support further refinement of DD for use in caries
      excavation and further research relating DD to other caries excavation endpoints.

PMID- 16433407
TI  - Evaluation of the elastic recovery of polyether impression materials.
AB  - PURPOSE: To evaluate and compare the effects of induced strain, time of
      straining, and loading time on the elastic recovery of two polyether impression
      materials and a vinyl polysiloxane reference material. METHODS: Specimens of the
      light and heavy-bodied types of the polyether materials P2 (P2L/H) and Impregum
      (IML/H) and of the vinyl polysiloxane impression material Flexitime (FLC/H) were
      loaded in a cone-plate rheometer with tensile strains between 16.4 and 60%, at
      different times after mixing, and at loading times between 1 and 10 seconds. The
      resulting permanent deformation was determined from creep curves. For each
      material and each variable condition six specimens were tested at ambient
      laboratory atmosphere. Regression analyses and ANOVA were used for statistical
      data analysis. RESULTS: Both induced strain, time of straining, and straining
      rate were significantly associated with the resulting permanent deformation of
      all materials, except FLC when loaded in the well-set stage between 1 and 10
      seconds loading time at 37.4% induced tensile strain (P< 0.001). Apart from P2
      the heavy-bodied impression materials showed significantly higher secondary creep
      (P < 0.05) than their corresponding light-bodied versions.

PMID- 16433408
TI  - Remineralization potential of an anticaries/antigingivitis mouthrinse.
AB  - PURPOSE: To assess the ability of a new formulation (Listerine with 0.022% NaF)
      to remineralize initially decalcified bovine enamel compared to a positive
      control, clinically established 0.022% NaF rinse. METHODS: A cyclic
      demineralization/remineralization in vitro model was utilized and the level of
      remineralization was monitored by examining the Knoop microhardness over 6 and 18
      D/T/R cycles RESULTS: (1) both the test formulation and positive control rinses
      were statistically significantly effective in remineralizing artificial lesions
      in vitro; and (2) the test formulation performed "at least as good as" the
      positive control. These results support the concept that the remineralization
      potential of the fluoride rinse is not adversely affected by the addition of
      essential oils.

PMID- 16433409
TI  - Rational design of thermally stable proteins: relevance to bionanotechnology.
AB  - Design of thermally stable proteins is spurred by their applications in
      bionanotechnology. There are three major issues governing this: first, the upper
      limit on the temperature at which proteins remain physiologically active and are
      available for technological applications (answers may emerge from the discovery
      of new, natural hyperthermophilic enzymes that are active above 125 degrees C or
      from the selection of mutants of hyperthermophilic enzymes that are more stable);
      second, the use of hyperthermophilic enzymes as molecular templates to design
      highly stable enzymes that have high activity at low temperatures; third, the
      link between rigidity and flexibility to thermostability and activity,
      respectively. We review progress in these areas.

PMID- 16433411
TI  - Reversible hole engineering for single-wall carbon nanotubes.
AB  - Experimental results are provided for reversible generation of holes on single
      wall carbon nanotubes and their closing by temperature treatment. The generation
      of the holes was analyzed by checking the amount of C60 fullerenes that can be
      filled into the tubes and subsequently transformed to an inner-shell tube. The
      concentration of the latter was determined from the Raman response of the radial
      breathing mode. The tube opening process was performed by exposure of the tubes
      to air at elevated temperatures. This process was found to be independent from
      the tube diameters. In contrast, the tube closing process was found to depend
      strongly of the tube diameter. For large diameter tubes (d = 1.8 nm) the
      activation energy was 1.7 eV whereas for the small diameter tubes this energy was
      only 0.33 eV. Optimum conditions for tube closing were found to be one hour at
      800 degrees C or 10 minutes at 1000 degrees C. From the almost identical Raman
      spectra for the tubes before and after engineering, a predominant generation of
      the holes at the tube ends is concluded.

PMID- 16433410
TI  - One-dimensional semiconductor nanostructures as absorber layers in solar cells.
AB  - The one-dimensional (1-D) nanostructures of cadmium chalcogenides (Il-VI: CdSe,
      CdTe), InP and GaAs (III-V), and the ternary chalcopyrites CulnS2, CulnSe2, and
      CulnTe2 (I-III-VI2) are the candidate semiconductors of interest as absorber
      layers in solar cells. In the confinement regime (approximately 1-10 nm) of these
      1-D nanostructures, the electronic energy levels are quantized so that the
      oscillator strength and the resultant absorption of solar energy are enhanced.
      Moreover, the discrete energy levels effectively separate the electrons and holes
      at the two electrodes or at the interfaces with a polymer in a hybrid structure,
      so that an oriented and 1-D nanostructured absorber layer is expected to improve
      the conversion efficiency of solar cells. The intrinsic anisotropy of Il-VI and l
      lll-VI2 crystal lattices and the progress in various growth processes are
      assessed to derive suitable morphological features of these 1-D semiconductor
      nanostructures. The present status of research in nanorod-based solar cells is
      reviewed and possible routes are identified to improve the performance of nanorod
      based solar cells. Finally, the characteristics of nanorod-based solar cells are
      compared with the dye-sensitized and organic solar cells.

PMID- 16433412
TI  - Photolithographic patterning of dendrimer monolayers and pattern-selective
      adsorption of linear macromolecules.
AB  - Alkyl groups of n-octadecyltrimethoxysilane (ODS) in a self-assembled monolayer
      on a silicon substrate were oxidized to carboxyl groups by partial irradiation of
      vacuum ultra-violet light under the photomask, producing a COOH/ODS line pattern.
      After active esterification of carboxyl groups, two kinds of amine-terminated
      dendrimers, poly(propyleneimine) and poly(amido amine) (PAMAM) dendrimers, were
      immobilized on a COOH line through amide-bond so that photolithographic
      dendrimer/ODS pattern was finally fabricated. Preparation was certified by atomic
      force microscopy (AFM) and surface-enhanced infrared absorption spectroscopy at
      transmission mode. Adsorption of linear macromolecules was examined on PAMAM
      dendrimer/ODS pattern. After adsorption of poly-L-glutamic acid (PGA) at a pH
      below alpha-helix--random coil transition, rod-shape texture was observed only on
      the dendrimer line in an AFM image. This texture is an aggregate of alpha-helical
      PGA. Sodium hyaluronate and DNA were also adsorbed selectively on the dendrimer
      line, keeping the line profile, although characteristic textures were not
      observed.

PMID- 16433413
TI  - Numerical simulation of light propagation through highly-ordered titania nanotube
      arrays: dimension optimization for improved photoabsorption.
AB  - Propagation of electromagnetic waves in the ultraviolet-visible range (300 to 600
      nm) through a unique highly-ordered titania nanotube array structure is studied
      using the computational technique of Finite Difference Time Domain (FDTD).
      Through numerical simulation the transmittance, reflectance and absorbance of the
      nanotube-arrays are obtained as a function of tube length and diameter. The
      nanotube-arrays are found to completely absorb light having wavelengths less than
      approximately 330 nm. For wavelengths above 380 nm absorption increases as a
      function of nanotube length, while above 435 nm absorption increases with
      decreasing pore size. Computational simulations closely match experimental
      measurements, indicating the suitability of the computational technique for
      guiding material optimization.

PMID- 16433414
TI  - Comparison of selective attachment and growth of smooth muscle cells on gelatin-
      and fibronectin-coated micropatterns.
AB  - Tissue engineering research has been on going for many years, people are making
      all the effort to explore the cell functions in cellular level and even in
      molecular level. Making the cells functional in an in vitro environment is a
      preliminary goal for the implantation and repair of complicated tissues/organs.
      Fabricating artificial ECM to mimic the in vivo environment is an essential
      approach in tissue engineering. The work in this paper is to study how rat aorta
      smooth muscle cells (RASMCs) behave in two engineered cell culture scaffolds:
      gelatin- and fibronectin (FN)-coated micropatterns. The investigation on the
      initial attachment and further growth of SMCs cultured on gelatin- and FN-coated
      micropatterns was addressed. This study focused on both the characterization of
      gelatin and fibronectin assembly properties and cell responses to these two
      protein-coated micropatterns. Thin film patterns with gelatin and fibronectin
      coatings were fabricated on microscope glass slides using photolithography,
      electrostatic layer-by-layer self-assembly and lift-off (LbL-LO) technologies. In
      this work, the scaffolds were built up by commonly used polyelectrolyte materials
      and proteins through LbL process, containing cationic
      poly(diallyldimethylammonium chloride) (PDDA), poly(allylamine hydrochloride)
      (PAH), anionic poly(sodium 4-styrenesulfonate) (PSS), gelatin and fibronectin.
      The resulting polyelectrolyte thin films were characterized by contact angle
      (CA), quartz crystal microbalance (QCM), atomic force microscopy (AFM), and
      fluorescence microscopy. CA measurement shows the consistent hydrophylicity of
      gelatin surfaces in different number of layers with LbL deposition method.
      Different from our previous QCM measurement of gelatin, fibronectin does not show
      high electrostatic attraction to either positively or negatively charged
      polyelectrolytes, although it can be weakly assembled to both polyelectrolyte
      surfaces. AFM images show Gelatin- and FN-coated micropatterns are around 50-60
      nm thick. RASMCs were cultured on these gelatin- and FN-coated micropatterns. It
      was observed that, for the cells cultured on gelatin-coated micropatterns, they
      initially landed on the gelatin-coated surface, not on the PDDA-coated surface in
      between. But further growth of the cells was affected by the shape of the
      patterns: strip pattern limited cell growth beyond the patterns, but square
      patterns could not. While, it was found interestingly, for the cells cultured on
      FN-coated micropatterns, SMCs initially landed on PDDA-coated surface, and then
      migrated to FN-coated both square and strip patterns. These findings indicate
      that both gelatin and fibronectin are adhesive proteins, but they have different
      effects on the initial attachment and later growth for SMCs.

PMID- 16433415
TI  - Nanoindentation on porous bioceramic scaffolds for bone tissue engineering.
AB  - We report nanoindentation mechanical properties measurements on porous ceramic
      scaffolds made for tissue engineering applications. The scaffolds have been made
      from tricalcium phosphate (TCP), hydroxyapatite (HA) nanopowder and mixed powders
      of HA (50 wt%) and TCP (50 wt%) using the polyurethane sponge method, which
      produces open porous ceramic scaffolds through replication of a porous polymer
      template. The scaffolds prepared by this method have a controllable pore size and
      interconnected pore structure. The crystal structures and morphology of porous
      scaffolds were determined by X-ray diffraction (XRD) and atomic force microscopy
      (AFM) respectively. Nanoindentation measurements to a depth of 600 nm showed a
      Young's modulus value of 10.3 GPa for HA+TCP composite scaffolds and 1.5 GPa for
      TCP scaffolds. The hardness values were 240 MPa for HA+TCP composites and 21 MPa
      for TCP sample respectively. The results showed that the mechanical properties of
      the biodegradable scaffolds can be considerably enhanced with the addition of HA
      while maintaining the interconnected open pores and pore geometry desirable for
      bone tissue engineering.

PMID- 16433416
TI  - Fabrication of photo-encoded beads for bioanalysis.
AB  - Encoding large libraries of biomolecules is important to the applications such as
      immunoassay, drug screening and so on. By now a number of encoding schemes have
      been proposed and developed. In this paper, a new encoding approach was proposed
      based on the photonic crystal beads and an apparatus was developed for the
      fabrication. Encoded beads, with diameters in the range between 0.2 mm and 3 mm,
      were prepared using polymer and pearl dye. Pearl dye is a kind of photonic
      crystal, the color of which is from the ordered nanostructure. Such a colorizing
      mechanism makes the color of pearl dye much stable to high temperature, UV
      irradiation or longtime storage comparing with the conventional dyes.

PMID- 16433417
TI  - Electrostatically stabilised nanoparticles: self-organization and electron-beam
      patterning.
AB  - The self-organisation of citrate- and magnesium oleate-stabilised gold
      nanoparticles on SiO2/Si substrates was investigated. In drop deposition,
      nucleation of citrate-stabilised gold nanoparticles was observed at the rim of
      the droplet, symmetric or multibranched dendroid gold structures were found in
      the area between the rim and the central part of the droplet, depending on the
      drying temperature. Homogeneous submonolayer nanoparticle coverage was obtained
      by immersion of amineterminated SiO2/Si surfaces into a citrate-stabilised
      colloidal gold acidic solution. Drop deposition of magnesium oleate-stabilised
      gold nanoparticles onto the SiO2/Si surfaces resulted in the formation of
      uniformly close-packed nanoparticle arrays. Under electron beam irradiation, no
      apparent changes were found for monolayer films of citrate-stabilized particles,
      but sintering of the nanoparticles was observed in multilayer films. In contrast,
      coalescence of magnesium oleate-stabilised gold nanoparticle occurred in
      monolayer films after electron irradiation.

PMID- 16433418
TI  - Synthesis, characterization, and optical properties of AuSe nanoalloys.
AB  - A solution phase approach to synthesize a new metal-semiconductor nanocomposite,
      AuSe nanoalloy has been reported. The synthesis has been achieved through UV
      photoactivation of preformed Au and Se nanoparticles in micelle. Non-ionic
      surfactant Triton X-100 was exploited as a micellar medium for effective fusion
      of gold and selenium particles under UV. Both physical and chemical studies have
      been performed to characterize the composition and morphology of the particles.
      UV-visible, TEM, SEM, XPS and AFM analyses were done for characterization
      purpose. The optical properties of nanocomposites have been substantiated through
      their interaction with a fluorescent probe, eosin in aqueous solution. The
      spectroscopic investigation of dye-metal-semiconductor assembly has been examined
      critically. It has been found that the dye experiences J and H types of
      aggregation on the surfaces of gold and selenium nanoparticles respectively.
      Again, the composition dependent change of the emission profile of the probe on
      different nanocomposite surfaces has been rationalized in accordance with the
      molecular dimerization of the dye.

PMID- 16433419
TI  - Nanorods of copper and nickel oxalates synthesized by the reverse micellar route.
AB  - Nanorods of nickel and copper oxalate have been synthesized by the reverse
      micellar route. Powder X-ray diffraction studies and thermo gravimetric analysis
      confirms the formation of monophasic NiC2O4 x 2H2O and CuC2O4 x H2O. Transmission
      electron microscopy shows that the as prepared nanorods of nickel and copper have
      diameter of 250 nm and 130 nm while the length is of the order of 2.5 microm and
      480 nm respectively. The aspect ratio of the nanorods could be modified by
      changing the solvent. The nickel oxalate nanorods appear very smooth with uniform
      length while the copper oxalate nanorods appear to be corrugated. Nickel oxalate
      dihydrate nanorods show an antiferromagnetic transition at T(N) = 34 K while the
      copper based nanorods show temperature independent paramagnetism.

PMID- 16433420
TI  - Electrohydrodynamic deposition of nanostructured lead zirconate titanate.
AB  - The deposition of a propanol-based lead zirconate titanate (PZT) sol using
      electrohydrodynamic atomization (EHDA) in the stable cone-jet mode was
      investigated. The droplets generated were deposited onto a copper substrate as a
      film, which was investigated using X-ray diffraction and scanning electron
      microscopy. The PZT film was shown to contain uniform nano-particles of PZT,
      which maintained their shape on sintering (650 degrees C, 1 hour) while forming
      the perovskite phase of PZT.

PMID- 16433421
TI  - Deposition of platinum nanoparticles on carbon nanotubes by supercritical fluid
      method.
AB  - Carbon nanotube-supported platinum nanoparticles with a 5-15 nm diameter size
      range can be synthesized by hydrogen reduction of platinum(ll) acetylacetonate in
      methanol modified supercritical carbon dioxide. X-ray photoelectron spectroscopy
      and X-ray diffraction spectra indicate that the carbon nanotubes contain zero
      valent platinum metal and high-resolution transmission electron microscopy images
      show that the visible lattice fringes of platinum nanoparticles are crystallites.
      Carbon nanotubes synthesized with 25% by weight of platinum nanoparticles exhibit
      a higher activity for hydrogenation of benzene compared with a commercial carbon
      black platinum catalyst. The carbon nanotube-supported platinum nanocatalyst can
      be reused at least six times for the hydrogenation reaction without losing
      activity. The carbon nanotube-supported platinum nanoparticles are also highly
      active for electrochemical oxidation of methanol and for reduction of oxygen
      suggesting their potential use as a new electrocatalyst for proton exchange
      membrane fuel cell applications.

PMID- 16433422
TI  - Size-induced changes in optical and X-ray photoelectron spectra of GaN
      nanoparticles deposited at lower substrate temperature.
AB  - This study reports the synthesis of GaN nanoparticles having hexagonal structure
      by a simple technique of activated reactive evaporation with substrates kept at
      comparatively lower temperatures than usually reported. By varying the substrate
      temperature from 30 degrees C to 350 degrees C, it is possible to vary
      nanoparticle sizes from 5-30 nm. X-ray diffraction and X-ray photoelectron
      spectroscopy analysis confirm the formation of GaN on quartz and silicon
      substrates at room temperature. The observed size dependent shift in energy
      position, large increase in full width at half maximum value of Ga 3d and N 1s X
      ray photoelectron spectroscopy peaks and blue shift in the optical absorption
      edge are related to nanoparticle character.

PMID- 16433423
TI  - Effect of air-pressure on room temperature hydrogen sensing characteristics of
      nanocrystalline doped tin oxide MEMS-based sensor.
AB  - Nanocrystalline indium oxide (In2O3)-doped tin oxide (SnO2) thin film sensor has
      been sol-gel dip-coated on a microelectrochemical system (MEMS) device using a
      sol-gel dip-coating technique. Hydrogen (H2) at ppm-level has been successfully
      detected at room temperature using the present MEMS-based sensor. The room
      temperature H2 sensing characteristics (sensitivity, response and recovery time,
      and recovery rate) of the present MEMS-based sensor has been investigated as a
      function of air-pressure (50-600 Torr) with and without the ultraviolet (UV)
      radiation exposure. It has been demonstrated that, the concentration of the
      surface-adsorbed oxygen-ions (which is related to the sensor-resistance in air),
      the ppm-level H2, and the oxygen (O2) partial pressure are the three major
      factors, which determine the variation in the room temperature H2 sensing
      characteristics of the present MEMS-based sensor as a function of air-pressure.

PMID- 16433424
TI  - Preparation and catalytic activity of Au-Pd, Au-Pt, and Pt-Pd binary metal
      dendrimer nanocomposites.
AB  - Catalytic activity of Au-Pt, Au-Pd, and Pt-Pd dendrimer nanocomposites for
      reduction of p-nitrophenol was investigated in water. The bimetallic dendrimer
      nanocomposites were prepared by simultaneous reduction with sodium borohydride in
      the presence of poly(amidoamine) (PAMAM) dendrimers with amine and carboxyl
      terminal groups. Average diameters of the obtained particles were 2-4 nm by
      transmission electron microscopy. From UV-vis spectroscopy, it was found that the
      particles were not mixtures of monometallic particles but binary ones. X-ray
      photoelectron spectroscopy showed that formation of binary composite particles
      prevents palladium atoms from oxidation. The Au-Pd and Pt-Pd binary particles
      exhibited higher catalytic activity than monometallic ones. On the other hand,
      catalytic activity of Au-Pt binary particle was comparable to that of platinum
      nanoparticles.

PMID- 16433425
TI  - Synthesis of gold nanotubes by sputtering of gold into porous materials.
AB  - Hollow 1-D gold nanostructures with controlled morphology could be readily
      obtained by RF-sputtering of gold into porous matrices (polycarbonate,
      polyester), used as scaffolds at low temperatures. Post-synthesis membrane
      etching by oxygen plasmas or in solution enabled the preparation of free-standing
      Au nanotubes maintaining the original morphology, that are attractive elements in
      device structures, such as biosensors for DNA chips or nanoelectrode ensembles.
      The present results appear extremely promising for the scale-up of different
      kinds of 1-D materials.

PMID- 16433426
TI  - Growth of carbon nanotubes at low powers by impedance-matched microwave plasma
      enhanced chemical vapor deposition method.
AB  - A solo carbon nanotube (CNT) was successfully grown on nickel electrodes by a
      microwave plasma enhanced chemical vapor deposition (MPECVD) method equipped with
      an impedance-matched substrate holder with the reaction gases composed of
      hydrogen (H2), carbon dioxide (CO2), and methane (CH4) mixtures. An introduction
      of carbon dioxide gas before CNTs growth, the substrate temperature can easily be
      reached above 610 degrees C even heated at a low microwave power. This can be
      enunciated from fact that carbon dioxide inherits with higher bond energy for
      molecular dissociation, lower thermal conductivity, and higher heat capacity in
      comparing to other gases. The electron field emissions for randomly aligned CNTs
      and well-aligned CNTs grown by MPECVD and by radio frequency assisted hot
      filament methods, respectively, are measured and compared. The higher field
      emission characteristic of the randomly aligned CNTs is presumed to be due to the
      protruded CNTs, which inheriting with less screening effect and manifesting with
      defects are crucial to play the effective emission sites.

PMID- 16433427
TI  - Mechanical testing of isolated amorphous silicon slanted nanorods.
AB  - Mechanical testing was performed on a new class of nanostructures-amorphous Si
      slanted nanorods of rectangular cross section, fixed at one end to the substrate.
      These nanorods were grown spatially well separated on nano-pillars under the
      oblique angle physical vapor deposition technique. Various samples with different
      dimensions and inclination angles were tested in bending using an atomic force
      microscope. The material response was elastic up to large stresses/deflections.
      The Young's modulus was calculated from the slope of the experimentally observed
      stiffness versus the geometrical factor common to all the samples and was found
      to be (94.14 +/- 10.21) GPa. No size effect of this parameter was observed within
      the accuracy of the present measurement.

PMID- 16433428
TI  - Role of Au nanoparticles in efficiency enhancement and green band emission
      quenching of blue polymer light emitting diodes.
AB  - We studied photoluminescence (PL) and electroluminescence (EL) properties of
      polymer light emitting diodes (PLEDs) constructed with polyconjugated polymers
      blends containing Au nanoparticles (DA-Au NPs; 5.3 nm +/- 1.1 nm in diameter)
      capped by dodecylamine. For the blue light emitting polyfluorene polymers,
      selective quenching of excimer peaks or so-called green bands was observed in PL
      as well as in EL when they were mixed with small amounts (1-4 wt%) of DA-Au NP.
      The influence of DA-Au NPs on the light-emitting characteristics of the PLEDs
      strongly depended on the nature of the matrix polymer, which was particularly
      conspicuous for the polymers whose emission wavelength matches or overlaps with
      the surface plasmon resonance wavelength region of Au nanoparticles. Especially,
      the purity of the blue color emitted by the poly [2,7-(9,9-di-n-dioctylfluorene)
      (PF) was greatly improved by Au NPs that suppressed the 'green band.' All the
      PLEDs doped with DA-Au NPs showed enhanced maximum external quantum efficiency
      and emitted light intensity when compared to undoped counterparts.

PMID- 16433429
TI  - Templated synthesis, characterization, and sensing application of macroscopic
      platinum nanowire network electrodes.
AB  - Novel platinum nanowire network electrodes have been fabricated through
      electrodeposition using mesoporous silica thin films as templates. These
      electrodes were characterized by X-ray diffraction, transmission electron
      microscope, and scanning electron microscope. The electrochemical properties of
      the electrodes, such as electrochemical active area and methanol oxidation, have
      also been studied. Compared with conventional polycrystalline Pt electrodes,
      these novel nanowire network electrodes possess high electrochemical active areas
      and demonstrate higher current densities and a lower onset potential for methanol
      electro-oxidation. Enzymatic Pt nanowire-network-based sensors show higher
      sensitivity for glucose detection than that using conventional polycrystalline Pt
      electrode. Such macroscopic nanowire network electrodes provide ideal platforms
      for sensing and other device applications.

PMID- 16433430
TI  - Pyroelectric and conduction properties of Z-type calix[4] acid Langmuir-Blodgett
      films.
AB  - Non-centrosymmetric Z-type Langmuir-Blodgett (LB) films were prepared by
      transferring a calix[4] acid monolayer from a subphase of Millipore water (18
      Momegacm(-1)) onto aluminised glass substrates. Electrical measurements were
      performed at room temperature on LB films with a sandwich structure comprising a
      50 nm thick thermally evaporated aluminium film. A pyroelectric figure of merit
      of 2.23 microC m(-2)K(-1) is reported for this LB system. The low voltage value
      of conductivity is 1.82 x 10(-12) Sm(-1). The electrode-limited Schottky effect
      is responsible for the conduction mechanism at a relatively high field due to the
      dc bias and the barrier potential height is determined to be 1.72 eV. The ac
      conductance for both samples shows a typical power law dependence with a value of
      approximately 0.86 for the exponent.

PMID- 16433431
TI  - Fabrication of optically enhanced ZnO nanorods and microrods using novel
      biocatalysts.
AB  - We developed a straightforward method to produce hexagonal ZnO nanorods and
      microrods using a novel biocatalyst, Magnetospirillum magnetotacticum. ZnO
      nanorods were synthesized homogeneously on growth substrates when the bacterial
      catalysts were deposited uniformly on substrates whereas ZnO microrods were
      formed when the catalysts were introduced to selective areas of growth substrates
      using microcontact printing. X-ray diffraction measurements reveal that these ZnO
      structures exhibit Wurtzite structures with preferential growth along [0001]
      direction. Room-temperature photoluminescence spectra of the as-synthesized ZnO
      nanorods and microrods show extremely strong and sharp UV emission at 390 nm and
      negligible green emission at 510 nm. Our results demonstrate that
      Magnetospirillum magnetotacticum is an effective catalyst for the growth of
      nanometer- and micrometer-sized ZnO structures with exceptionally high-quality
      optical properties. These defect-free ZnO nano-and micro-materials, when combined
      with microcontact printing techniques to achieve patterned growth over large
      areas of substrates, can facilitate their photonic-based applications as
      optoelectronic devices and chemical/biological sensors.

PMID- 16433432
TI  - Preparation and optical properties of Au/Teflon nanocomposites.
AB  - Using thermal deposition technique, we have prepared Au/Teflon thin films on
      glass substrates. To control the film microstructure, both TEM and AFM
      characterization have been carried out. The visible optical transmission spectra
      have been measured in-situ. The peak positions and linewidths in the spectra have
      been identified in terms of the gold nanoparticle shape, size, and arrangement.
      The results obtained provide evidence for formation of both sphere-like and
      cylinder-like gold nanoparticles in the films. The fraction of each kind of the
      particles depends on whether the plasma treatment has been used. The treatment is
      shown to enhance the fraction of the cylinder-like particles.

PMID- 16433433
TI  - Ultra long SiC/SiO2 core-shell nanocables from organic precursor.
AB  - Ultra long SiC core and SiO2 shell nanocables have been prepared by pyrolysis of
      poly(dimethyl siloxane) at 1050 degrees C in flowing Argon. The longest nanocable
      can be up to at least 6 mm. Transmission electron microscopy observations
      indicate that the diameter of the cores varies from about 3 to 18 nm, and the
      thickness of the outer sheaths varies from about 6 to 45 nm and that the cores
      are crystalline and the sheaths are amorphous. The growth of the nanocables may
      be governed by a chemical vapor solid process. The nanocables exhibit good
      photoluminescence property.

PMID- 16433434
TI  - A simple route to platinum and Pt-based composite nanotubes.
AB  - Platinum (Pt) and Pt-based composite nanotubes were fabricated by a facile
      dipping method within alumina templates. The morphology, structure, and
      composition of the nanotubes were characterized by SEM, TEM, and EDX. A hydrogen
      sensor based on Pt/TiO2 composite nanotubes showed high hydrogen sensitivity.

PMID- 16433435
TI  - Time-resolved optical sensing of oligonucleotide hybridization via Au colloidal
      nanoparticles.
AB  - Au nanoparticles have distinctive absorption spectra whose peak position or
      particle plasmon resonance wavelength is highly sensitive to molecule adsorption
      on their surfaces. Spherical Au nanoparticles are surface-modified by amino
      functionalized self-assembly-monolayer and used as optical probes in the
      fluorescence-label-free spectroscopic detection of sub-nanomole oligonucleotides.
      Time-resolved studies of the immobilization and hybridization of oligonucleotides
      on the surface of Au nanoparticles were carried out. By measuring peak shift of
      absorption spectra of the Au colloidal nanoparticles over time, the samples of 15
      nM 20 mer target and mismatched oligonucleotides are distinguished by their
      different influences on the particle plasmon resonance wavelength. The approach
      presented in this paper extends the application of Au nanoparticles as the
      optical probe in oligonucleotide recognitions without prior sample labeling.

PMID- 16433436
TI  - [Spinal cord trauma: epidemiology and pre-hospital management].
AB  - In France, about 2000 people suffer spinal cord injuries each year. Most patients
      are young men involved in road accidents and most have cervical lesions.
      Emergency pre-hospital care is crucial, as the lesions are potentially life
      threatening and can have devastating functional consequences. The possibility of
      spinal cord trauma must always be kept in mind, and the spine must be
      immobilized. The initial neurological examination is extremely important. Initial
      medical care should target an average systolic blood pressure above 80 mmHg,
      ensure adequate ventilation, maintain the body temperature over 36 degrees C, and
      control hyperglycemia. The patient should be transported rapidly to a specialized
      spinal trauma unit.

PMID- 16433437
TI  - [Pathophysiology and treatment of spinal cord injury].
AB  - Spinal cord injury can lead to devastating functional disability.
      Pathophysiological studies show that, very early after the initial trauma,
      secondary damage is caused by toxic phenomena involving excitatory amino acids
      (excitotoxicity). The use of specific antagonists can attenuate this secondary
      damage in murine models. However, the kinetics of this phenomenon must be
      precisely documented before launching clinical trials of multidrug therapy.
      Axonal regeneration, previously considered impossible within the mammalian
      central nervous system, depends on appropriate control of glial reactivity. This
      may be achieved through gene therapy (si RNA) targeting glial obstacles. Finally,
      the existence in the spinal cord of autonomous centers such as the locomotor CPG
      suggests that cell therapy-based approaches may also be effective.

PMID- 16433438
TI  - [Traumatic lesions of the spinal cord. Management in the hospital: the orthopedic
      surgeon's point of view].
AB  - Initial presurgical management of spinal injuries with spinal cord damage
      includes cardiorespiratory intensive care, a precise neurologic examination, and
      a complete radiological work-up with simple films, computed tomography, and also
      magnetic resonance imaging if there is a conflict between the imaging results and
      clinical findings. The structural lesion can then be staged, using a reproducible
      system with prognostic value for instability. Reduction, decompression and
      stabilization are the three main objectives of orthopedic management. In our
      unit, reduction is achieved either with external maneuvers (traction applied with
      cranial tongs for cervical injuries, or placing long cushions under the patient
      with thoracolumbar injury) or by using internal, surgical techniques. Instead of
      waiting for decompression by natural remodeling, surgeons should perform
      decompressive procedures. Surgical stabilization includes osteosynthesis and
      grafting, which permits more active patient care. The interval between injury and
      surgery is crucial. It should be as short as possible in case of severe
      instability or when the lesion cannot be reduced. We recommend the anterior
      approach to the lower cervical region. The posterior approach is simpler for
      urgent treatment of thoracolumbar lesions. Spinal cord injuries in children pose
      two specific problems: that of spinal cord damage with no visible bony lesions;
      and that of subsequent spinal deformities (scoliosis, hypokyphosis, or
      hyperlordosis). The most common spinal cord injuries in the elderly involve
      hyperextension in patients with cervical canal stenosis. The incidence of spinal
      damage, with or without spinal cord involvement, is increasing Instability being
      rare in such cases, the primary objectives of surgery are usually decompression
      and repair.

PMID- 16433440
TI  - [Surgical repair of spinal cord injuries].
AB  - Spinal cord rupture is still incurable. Axons regenerating from the brain do not
      advance through the damaged cord towards peripheral motoneurons. The reasons for
      this "nonpermissiveness" are unclear. The author's research started in 1980 on
      rats and monkeys, with attempts to connect the lateral tract of the cord,
      upstream of the lesion, to the muscles, by means of autologous grafts. This
      operation was subsequently performed on fully informed volunteers with total cord
      rupture between T8 and T11. The first patient regained a rudimentary but
      effective gait. This connection of upper motoneurons with peripheral muscle
      nerves works even when the activating axons derive from cells dispersed among
      different regions of the brain cortex but that fire together, providing selective
      contraction of single muscles. Furthermore, this functioning occurs even though
      upper motor neurons use the neurotransmitter glutamate, whereas motor endplates
      normally have acetylcholine receptors. In fact, immunoblot analysis of ChAT
      VAChT, Vglu-1 GluR1 and GluR2 shows that motor endplate receptors switch from
      choline to glutamine.

PMID- 16433441
TI  - [Surgical rehabilitation of upper limb function by tendon transfer in
      tetraplegia].
AB  - Patients with cervical spinal cord injury have partial paralysis of their upper
      limbs, depending on the precise level of the injury. Twenty years ago, attempts
      at surgical rehabilitation of upper limb function in such patients started with
      tendon transfers, along with tenodeses, and some arthrodeses. These procedures
      are performed at least one year post-trauma. Depending upon the level of the
      injury, they usually significantly improve the functional autonomy of these
      otherwise severely handicapped patients. It is estimated that 60-70% of all
      tetraplegic patients can benefit from this type of surgery.

PMID- 16433442
TI  - [Rehabilitation of spinal cord injury patients].
AB  - The life expectancy of patients with spinal cord injury has increased linearly in
      the past five decades, but continues to be below that of their non disabled
      peers. This improvement was achieved through better knowledge of the
      pathophysiology of the multisystem impairments caused by spinal cord injury. The
      main treatment goals in spinal cord injury are to prevent complications, to
      obtain optimal function (depending on the affected neurological level), to
      facilitate social re-integration, and to provide specialized follow-up throughout
      life. This comprehensive management must be provided in spinal units, using a
      multidisciplinary approach.

PMID- 16433443
TI  - [Spinal muscular atrophy. A 4-year prospective, multicenter, longitudinal study
      (168 cases)].
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder
      characterised by motoneuron degeneration in the anterior horn of the spinal cord
      and in the bulbar nuclei. The various types of SMA are linked to the 5q13 locus
      in 95 % of cases. In the absence of an effective specific treatment, orthopaedic
      and respiratory management can significantly improve the prognosis. To study the
      contemporary natural history of SMA and to identify clinical and non invasive
      prognostic criteria, 168 patients with SMA were recruited in 6 hospital units
      (Lille, Lyon, Marseille, Paris) during a 4-year prospective multicenter follow-up
      study (1998-2002). Follow-up has now lasted at least 4 years in 151 cases (90%),
      and 24 of these patients have died Disease outcome was appraised by using three
      criteria: muscle strength, the sum of the motor function and examination index
      (IFM), the respiratory muscle paralysis index (IMR), and the dorsal decubitus
      forced vital capacity/theoretical index (ICV/CT). Statistical analysis showed a
      significant worsening (about 20%) of the three criteria during follow-up. The
      motor function and examination index (IFM) is particularly interesting: the
      difference between initial and final status was significant in all age groups and
      in all three types of the disease. The IFM may thus be useful as the main outcome
      measure during therapeutic trials.

PMID- 16433444
TI  - [New pathophysiological concepts on aspirin hypersensitivity (Widal syndrome);
      diagnostic and therapeutic consequences].
AB  - Hypersensitivity to aspirin usually takes the form of a clinical syndrome
      combining chronic rhinitis, nasal polyposis and asthma attacks that are
      exacerbated by aspirin or other non steroidal anti-inflammatory drugs (NSAIDs).
      This syndrome, first described by Widal in 1922, is very frequent: it affects
      nearly 15% of asthmatic patients and is usually associated with severe and
      sometimes fatal asthma. In other instances, hypersensitivity to NSAIDs manifests
      in the form of skin lesions, such as urticaria and angioedema. Until recently,
      the pathophysiological mechanism of NSAID hypersensitivity was somewhat
      mysterious. The fact that the main mediators involved are sulfidoleukotrienes
      (LTC4, LTD4, LTE4) and that the drugs responsible all inhibit cyclooxygenase-1
      (COX-1), pointed to a pharmacogenetic abnormality of arachidonic acid metabolism.
      An immunopharmacological study of basophil activation (detected by flow
      cytometry), sulfidoleukotriene production in the presence of NSAIDs in vitro, and
      other related studies reviewed here have revealed that: a) basophils from
      patients with the Widal syndrome are hyperactivated in a non specific manner,
      probably related to chronic inflammation in the skin or airways; b) these
      hyperactive basophils produce increased amounts of sulfidoleukotrienes but
      decreased amounts of PGE2 when exposed to NSAIDs in vitro. These observations led
      to the development of an in vitro diagnostic test which, in many cases, can
      replace challenge tests. The pathogenic mechanism of the Widal syndrome now
      appears to involve the combined effects of chronic inflammation (causing non
      specific cellular hyper-reactivity, particularly of mast cells, basophils and
      eosinophils) and a pharmacogenetic abnormality of arachidonic acid metabolism in
      response to NSAIDs. This leads to sulfidoleukotriene overproduction and to a
      decrease in the anti-inflammatory prostaglandin PGE2. This concept is compatible
      with the onset and outcome of most cases of the Widal syndrome, and provides a
      therapeutic rationale.

PMID- 16433445
TI  - [Legionella: from environmental habitats to human disease].
AB  - Water is the main reservoir for legionellae, and these bacteria are found in
      freshwater environments worldwide. Legionellae survive in aquatic and moist soil
      environments, in biofilms, as intracellular parasites of free-living protozoa.
      Protozoa naturally present in the environment support the intracellular growth of
      legionellae in vitro. Much of our understanding of the pathogenesis of
      legionellosis is based on studies of the infective process in protozoa and human
      cells.

PMID- 16433446
TI  - [Hereditary recurrent fever syndromes].
AB  - Four diseases presenting mainly as intermittent bouts of inflammatory symptoms
      have been clinically and genetically characterized. At the head of this group is
      familial Mediterranean fever, which affects thousands of patients of
      Mediterranean ancestry. The other three entities are the tumor necrosis factor
      receptor superfamily 1A-associated periodic fever syndrome (TRAPS) with a
      dominant mode of inheritance; hyperimmunoglobulinemia D and periodic fever
      syndrome (HIDS); and the most recently recognized entity, which includes Muckle
      Wells syndrome, familial cold urticaria, and the chronic infantile neurological
      cutaneous and articular (CINCA) syndrome. Proper diagnosis of these entities is
      needed to begin specific clinical and therapeutic management.

PMID- 16433447
TI  - [BCG in Europe in 2004].
AB  - BCG immunization policies are somewhat uniform in eastern Europe. The incidence
      rates of tuberculosis are already very high, and are increasing. WHO
      recommendations, ie. BCG immunization by intradermal injection at birth or as
      soon as possible after birth are implemented. In western countries, the incidence
      rates of tuberculosis are not clearly related to the local immunization policy.
      Some countries still immunize all children at birth or later, while others only
      immunize at-risk groups. The definition of the risk also differs from one country
      to another Finally, some countries do not offer immunization at all. The reasons
      for these disparities are examined, together with their implications for future
      French policy

PMID- 16433448
TI  - [Epidemiology of tuberculosis in France in 2003].
AB  - Tuberculosis is still a concern in France, especially in the Paris region and
      among people originating from highly endemic countries. In 2003, 6098 cases of
      tuberculosis were notified in France (10.2 per 100000). The patients' median age
      was 42 years, and 61% of patients were male. Most cases involved pulmonary
      tuberculosis (71.7%), but there were also 113 cases of tubercular meningitis
      (1.9%). Among documented cases, 43.9% were of foreign origin and 47.8% of
      patients were born abroad. The incidence among people born in France declined
      year on year until 2003, but has increased in the last two years in the 0- to 14
      year age group. At the same time the incidence of tuberculosis has been
      increasing among young people born in sub-Saharan Africa, and the number of cases
      due to multidrug-resistant strains is also increasing. Official guidelines have
      been updated in order to improve the prevention and control of tuberculosis.
      Enhanced surveillance and appropriately funded public health initiatives are
      needed to reinforce the fight against tuberculosis in France.

PMID- 16433449
TI  - [The genetic determinism of polygenic diseases].
AB  - Progress in molecular biology has opened the way to identifying genes involved in
      predisposition to multigene diseases. The two methods currently used for this
      purpose--analysis of candidate genes and systematic genomic screening--have given
      interesting but only very partial results. The problem is complicated by the
      large number of genes involved, their low penetrance, and linkage disequilibrium.

PMID- 16433450
TI  - [Gene therapy of severe combined immunodeficiency disease: proof of principle of
      efficiency and safety issues. Gene therapy, primary immunodeficiencies,
      retrovirus, lentivirus, genome].
AB  - Inherited defects in T lymphocyte development (severe combined immunodeficiencies
      SCID) are considered the best available models to assess the effectiveness of
      gene therapy. Retroviral vectors have been successfully used ex vivo to transduce
      hematopoietic precursors from patients with two forms of SCID, namely X-linked
      SCID and ADA deficiency. Fifteen out of 16 patients with XL-SCID and 4 out of 4
      patients with ADA deficiency have benefited from gene therapy. Correction of the
      immunodeficiency has been maintained now for 6 years in the first patients to be
      treated. These results provide clear-cut proof of the principle of gene therapy
      in relevant clinical models. However, three patients with XL-SCID have developed
      a severe complication after gene therapy, consisting of leukemia-like clonal
      lymphocyte proliferation. One of the three patients has died from this
      complication. It is due to provirus insertion within or close to proto-oncogenes,
      and to the enhancer activity of the viral LTR on targeted proto-oncogenes. Vector
      modifications, based mostly on inactivating the enhancer activity of the LTR,
      should preserve efficacy while improving safety.

PMID- 16433451
TI  - [Cystic fibrosis: chemical drugs to cure genetic diseases].
AB  - Cystic Fibrosis is the most common lethal genetic disease among Caucasian
      population. Despite considerable efforts, no significant progress has been so far
      achieved by gene therapies approaches. On the basis of a surprising clinical
      observation, we have developed an approach using anti-cancer drugs promoting the
      over expression of ABC transporters closely related to the deficient protein
      CFTR, which seem able to share functions with it and to restore the missing
      function(s).

PMID- 16433452
TI  - [Hereditary predisposition to cancer].
AB  - Cancer is a disease resulting from complex patterns of genetic alterations that
      lead to malignant transformation. As such, cancer is a genetically determined
      disease. The vast majority of cancers are sporadic and non-heritable: genetic
      alterations are acquired during life, notably by exposure to genotoxic agents.
      However, most cancer types also have hereditary forms, reflected in extreme
      situations by family clusters. These forms, which represent 2 to 5% of all
      cancers, result from transmission of germline mutations which considerably
      increase the risk of cancer. Over the past fifteen years, hereditary cancers have
      raised much interest in the scientific and medical communities.

PMID- 16433453
TI  - [Prevention of air pollution by indoor tobacco smoke in France].
AB  - A majority of smokers and non smokers find ambient tobacco smoke unpleasant.
      Passive smoking can cause sudden infant death, lung cancer and coronary heart
      disease. At least 3000 non smokers die as a result of passive smoking each year
      in France. Failure to properly implement Evin's law of 1991 explains why non
      smokers in France are still not protected. Scientific knowledge and public
      opinion support a total ban on smoking in all public places and working areas.

PMID- 16433454
TI  - [Medical liability. Comparative compensation for personal injury in Europe].
AB  - European institutions apply a number of common principles to medical liability
      and compensation. The Scandinavian patient insurance system, based on listed
      criteria, is independent from the notion of "fault", unlike in the rest of
      Europe. However, since March 2002, French law has also allowed for compensation
      of major medical accidents, regardless of the notion of fault. On the eve of
      harmonization, two statutory bases must be created. The first is a common
      European list of recoverable medical damages. Yvonne Lambert-Faivre's recent work
      offers a convenient guide in this respect. The second--pecuniary quantum of
      damages--should be founded on Courts of Appeal rulings on personal medical
      injury. Common trends can be identified in nearly all European countries. Despite
      the subsidiarity principle, a common road towards harmonizing medical accident
      compensation systems can be found.

PMID- 16433455
TI  - [The quest for an HIV vaccine].
AB  - At least 49 phase I trials of candidate vaccines for HIV/AIDS, together with two
      phase II trials and two phase III trials have been completed since the mid 1980s,
      involving more than 35 different vaccine formulations, 14 different adjuvants and
      more than 12000 volunteers. Although several neutralizing epitopes have been
      identified on the surface of the virus glycoprotein spikes, the goal of an HIV
      envelope-based vaccine capable of eliciting broadly reactive neutralizing
      antibodies is elusive. A gp120-based vaccine, which was tested in two phase III
      trials (one in the USA and the other in Thailand), was found to have no
      protective efficacy when injected every 6 months. The observation that, in the
      monkey model, both viremia (virus load) and clinical outcome are controlled by
      the CD8+ T cell response, prompted the development of an array of candidate
      vaccines capable of inducing HIV-specific T cell responses. A series of HIV
      vaccines based on live virus vectors are already undergoing clinical studies,
      including a live recombinant canarypox virus vaccine (ALVAC), which is in phase
      III trials in Thailand, a non-replicative adenovirus type 5 (Ad5) vaccine, which
      is entering a phase II trial in the USA and the Caribbean, and live recombinant
      vaccines based on the attenuated vaccinia virus MVA vector, which have already
      completed several phase I studies, used either alone or combined with DNA vaccine
      priming. A whole array of other vaccines based on live vectors, DNA, peptides and
      other designs, are being tested in nonhuman primates. None of these vaccines has
      been able to prevent infection following experimental challenge, but all were
      found to control viral load and to prevent CD4 cell loss. T cell-stimulating
      vaccines are thus unable to prevent infection but prevent or slow disease
      progression by controlling virus replication. Their efficacy in humans remains to
      be determined.

PMID- 16433456
TI  - [Stress, depression and cerebral plasticity: an update of clinical and
      experimental findings].
AB  - Recent studies of neuroplasticity in stress and depression have given rise to new
      hypotheses on the neural bases of these disorders. Based on data from imaging
      studies, cellular and molecular biology, and animal models, this approach could
      help to understand certain clinical findings, and especially cognitive
      impairments. Some antidepressants have effects on neuroplasticity, in addition to
      their symptomatic effects on depression.

PMID- 16433458
TI  - [A blinding orphan disease: high myopia].
AB  - High myopia is the fifth cause of legal blindness in France. Myopic blindness is
      somewhat neglected, however, because it is poorly understood and untreatable.
      Certain mechanisms of this visual handicap have been elucidated by the use of new
      imaging technologies, raising new therapeutic possibilities.

PMID- 16433457
TI  - [Oxygen and wound healing].
AB  - It has long been recognized that normal healing is dependent on the oxygen
      gradient in the wound Hypoxia can slow or arrest the healing process and augments
      the risk of infection. While hypoxia triggers neoangiogenesis, normal tissue
      oxygen pressures are mandatory for migration of repair cells (macrophages,
      fibroblasts), production of collagen precursors and, thus, for wound repair with
      good mechanical properties. Recent studies have identified the underlying
      molecular mechanisms of wound repair. In clinical practice, hyperbaric oxygen
      therapy is to treat problem wounds like diabetic foot lesions, arterial ulcers,
      and radionecrosis. Direct or indirect measurement of oxygen tissue pressure can
      help to select patients and to monitor treatment outcome.

PMID- 16433459
TI  - [Robotic surgery: toy or tool?].
AB  - Telemanipulation has been developed for industrial purposes since the 1970s. More
      recently, telemanipulated arms entered the operating room. This paper briefly
      describes the history of surgical robotics and discusses the advantages and
      disadvantages for both patients and surgeons. The authors advocate the
      development of robotic surgery, as it facilitates the training of young surgeons
      and can be useful during certain phases of an operation. Thus, robotic surgery is
      more a promising tool than a simple toy.

PMID- 16433460
TI  - [Melatonin: what for?].
AB  - Melatonin (N-acetyl-5 methoxy-tryptamine) is a hormone secreted mainly by the
      pineal gland or epiphysis; it is also produced, but in much smaller quantities,
      by the retina. The key enzyme in melatonin synthesis is N-acetyl-transferase
      (NAT) whose activity increases during darkness. This explains why melatonin is
      mainly secreted at night. The circadian rhythm of melatonin synthesis is
      controlled by the suprachiasmatic nuclei--the "biologic clock". This clock itself
      functions rhythmically, being entrained by environmental synchronizers. According
      to the time of exposure, light has two effects on melatonin secretion, either
      suppressing or shifting its secretion (phase-response curve). Exposure to light
      in the morning advances the phase of the rhythm, while exposure in the evening
      delays it. Melatonin works in the opposite way, acting as a light signal
      transducer, and relaying information on the duration of day and night. Exogenous
      melatonin can synchronize some circadian rhythms, such as body core temperature.
      Current research is focusing on the properties of melatonin (and of light) as a
      resynchronizing agent in situations such as aging, blindness, shift work, night
      work, phase-advanced or phase-delayed sleep syndrome, and jet lag. Melatonin also
      has strong antioxidant properties (stronger than those of vitamin E), and an
      oncostatic action. Interestingly, three recent epidemiological studies show that
      women who work exclusively at night for long periods have a significantly
      elevated relative risk of breast cancer (RR 1.1-1.6). Other studies are required
      to confirm these results.

PMID- 16433461
TI  - [Myocardial effects of nitric oxide, NO. Clinical and experimental evidence].
AB  - The vasodilatory properties of nitric oxide (NO) are well documented, but its
      direct effects on myocardial contractility are somewhat controversial. The
      present report follows a series of articles in which we reported the
      translocation of NO synthase isoforms both after myocardial infarction in aged
      rats and in human heart failure (HF). This redistribution is due to nNOS1
      translocation from the sarcoplasmic reticulum to the caveolae in the outer
      membranes. Translocation is determined by strong interactions between the enzyme
      and caveoline-3 (a marker of caveolae). It suggests a regulatory role of nNOS1 in
      both normal inotropism and HF. The physiological consequences of this
      translocation were studied in a well-documented experimental model of myocardial
      infarction with HF in adult rats. Myocardial function was analyzed before and
      after adrenergic activation, both ex vivo on isolated hearts and in vivo with a
      Millar probe.--In rats, as in humans, the level of nNOS1 is enhanced, and this is
      associated with translocation to the caveolae. Such a process is seen in both
      humans and rats with HF.--In HF, ventricular elastance (E(s), in mmHg/microL: a
      load-independent measure of contractility) is reduced, and the time constant of
      relaxation, tau, is prolonged. In basal conditions, in non HF controls, specific
      nNOS1 inhibition by L-VNIO induces a 33% increase in E(s) and a 17% increase in
      the time constant of relaxation. The response to an adrenergic stimulation is
      attenuated in HF. The main result of this work is that pharmacological inhibition
      of nNOS1, either ex vivo with L-VNIO, or in vivo with SMTC, normalizes the
      adrenergic response of failing hearts. nNOS1 translocation is thus a major
      contributor to the autocrine regulation of contractility in HF, and is probably
      responsible for hampering the adrenergic response in HF.

PMID- 16433462
TI  - [In vitro generation of mature and functional human red blood cells: a model with
      multidisciplinary perspectives].
AB  - We describe a technical approach permitting massive expansion of CD34+ stem cells
      (up to 1.95 x 10(6)-fold) and their full ex vivo conversion into mature red blood
      cells (RBCs). This three-step protocol can be adapted to hematopoietic stem cells
      (HSC) of various origins. First, cell proliferation and erythroid differentiation
      are induced in serum-free media supplemented with stem cell factor, interleukin-3
      and erythropoietin (Epo) for 8 days. The cells are then co-cultured with either
      the murine stromal cell line MS-5 or human mesenchymal cells for 3 days in the
      presence of Epo alone. Finally, all exogenous factors are withdrawn and the cells
      are incubated on a simple stroma for up to 10 days. The ex vivo microenvironment
      strongly influences both the terminal maturation of erythroid cells and
      hemoglobin (Hb) synthesis. Critically, in vitro-generated RBCs have all the
      characteristics of functional native adult RBCs in terms of their enzyme content,
      membrane deformability, and capacity to fix and release oxygen. In addition,
      their behavior in the murine NOD/SCID model mirrors that of native RBCs. This new
      concept of "cultured RBCs" (cRBC) has major implications for basic research on
      terminal erythropoiesis and for patient management. Currently, the potential
      yield of functional red cells is compatible with clinical requirements, as
      several units of packed RBCs can be produced from a single donation. Importantly,
      infused cRBC would all have a life-span of about 120 days, whereas the mean half
      life of normal donor RBCs is only 28 days. This would help to minimize the
      transfusion exposure of patients requiring regular treatment, thereby reducing
      the risk of iron overload and allo-immunization. The use of autologous CD34+
      cells isolated from leukapheresis samples could be beneficial for patients who no
      longer tolerate allogeneic RBCs. This new method should also prove useful for
      analyzing the mechanisms of terminal erythropoiesis, including hemoglobin
      synthesis. Finally, it could provide a tool for investigating the lifecycle of
      blood parasites such as Plasmodium, the agent of malaria.

PMID- 16433463
TI  - [Neutrophilic dermatosis and neutrophil disorders. A study of 31 clinical cases].
AB  - Neutrophilic diseases are a group of disorders--mainly dermatoses--in which
      polymorphonuclear neutrophils accumulate in the absence of an identified
      pathogen. Such neutrophil infiltration can lead to a variety of clinical
      manifestations, including inflammatory disorders of the digestive tract, and
      hematological and rheumatological disorders; monoclonal or polyclonal circulating
      IgA levels are elevated, and the disorders are sensitive to drugs acting on
      neutrophils. Other disorders associated with neutrophil accumulation do not share
      these criteria. Non neutrophilic manifestations may also be present, and
      determine the prognosis. Neutrophilic dermatoses are often chronic and relapsing
      remitting. Spontaneous regression occurs in some cases. It is unclear whether
      these pleomorphic disorders should be grouped together under a single heading In
      addition, the causes of the neutrophil accumulation are unknown. During the past
      five years, we have managed 31 patients with neutrophilic dermatoses. Here we
      describe our findings and review previous reports.

PMID- 16433464
TI  - [Schizophrenic disorders: current etiologic and clinical knowledge].
AB  - Brain anomalies associated with schizophrenic disorders may be of a cognitive,
      neurophysiological or neurological nature [the latter being relatively minor and
      nonspecific]. Brain imaging has revealed early anomalies such as cortical
      subcortical atrophy and abnormal gyration. These anomalies can also be present in
      relatives free of schizophrenic symptoms. This raises the question of what
      determines the transition from vulnerability to clinical onset. There is now
      evidence that schizophrenic disorders are true brain diseases. This is based on
      neuropathological studies, brain imaging and clinical findings such as "soft"
      neurological signs (pyramidal and extrapyramidal symptoms, coordination
      difficulties, etc.). Cognitive dysfunctions such as attention and memory
      disorders and abnormal verbal fluency have also been described. Oculomotor
      pursuit and auditive evoked potentials have identified specific
      neurophysiological disorders such as N300 and P50 wave modifications.
      Schizophrenic disorders can also be associated with neuronal abnormalities,
      notably affecting factors involved in synaptic transmission and plasticity. For
      example, BDNF protein deficit is linked to certain late-onset forms of
      schizophrenia. Genetic studies are no longer focusing on a possible disease
      genotype but rather on phenotypic characteristics determined by simpler genotypes
      (P50 wave modulation, COMT and BDNF genes). The ultimate objective is to identify
      high-risk subjects, in order to shorten the treatment delay and thereby improve
      long-term outcome. The benefit of primary prophylaxis remains to be determined,
      however.

PMID- 16433465
TI  - [Alternative splicing: a novel pharmacological target with wide therapeutic
      potential].
AB  - Alternative splicing is a process by which a single stretch of genomic DNA yields
      several mRNAs encoding different proteins. Once believed to be a marginal
      phenomenon, alternative splicing now appears to be widespread among higher
      organisms and to be behind a large repertoire of human diseases. It involves a
      flexible mechanism for selecting splice sites, based on regulatory sequences
      recognized by cognate trans-acting protein factors (stimulatory SR proteins, or
      their antagonists). This RNA-protein interaction provides two types of targets
      for therapeutic manipulation. Masking regulatory RNA sequences with an antisense
      strategy is the most obvious, and encouraging results are beginning to accrue.
      Our lab is currently developing an entirely new approach in which activating
      proteins are targeted by small chemical molecules. A large screening program has
      been conducted with the chemical library from the Curie Institute. Several
      molecules (all indole derivatives) were found to counter the stimulatory effects
      of individual activating proteins, and have been selected for further
      development.

PMID- 16433466
TI  - [FDG (18 fluorodeoxyglucose) positron emission tomography and breast cancer].
AB  - Positron emission tomography (PET) is a metabolic radionuclide imaging method in
      which a tracer labeled with a positron emitter is detected with a dedicated
      system. 18F-fluorodeoxyglucose (FDG) accumulates in tumor cells because of their
      increased glycolytic activity, and is thus widely used as a tracer in oncology.
      This increased metabolic activity precedes morphologic modifications, making FDG
      PET a very useful tool for detecting and staging cancer. It can also be used to
      characterize morphologic changes, differentiating not only between benign and
      malignant lesions, but also between viable tumor cells and areas of necrosis
      and/or fibrosis induced by treatments. Being a whole-body examination, it allows
      malignancies to be staged in a single procedure. Systems combining PET and CT
      (computed tomography) offer improved performance, providing both metabolic and
      anatomical data. This technique appears to be useful for initial breast cancer
      staging, especially of locally advanced forms and suspected recurrences (increase
      of isolated tumor marker). Early studies of PET evaluation of responses to
      hormonal and/or cytotoxic therapies have also given very promising results.
      However, this technique does not seem sufficiently sensitive to be included in
      the initial screening or diagnosis of primary tumors, owing to its limited
      resolution (about 5 mm) and its restricted availability. This approach is poorly
      sensitive when used for axillary assessment, but offers good specificity.

PMID- 16433467
TI  - [Surgical complications and the legal expert medical evidence of attributability
      and causality].
AB  - The cause-effect relationship is a cornerstone of legal decisions. In the medical
      sphere, the expert charged with determining the attributability of adverse
      effects must take into account both the likely pathophysiological mechanism and
      the chronology, based on common sense. When proven by the expert, attributability
      -a medical concept--allows the judge to determine the legal implications. The
      expert report should describe the incriminated actions and their observed adverse
      effects, distinguish what is clearly false from what is probably true, state only
      what is certain, and clearly identify any doubts.

PMID- 16433468
TI  - Hepatitis A and B virus immunization in HIV-infected persons.

PMID- 16433469
TI  - Another year, another day.

PMID- 16433470
TI  - A rapid HIV testing program for labor and delivery in an inner-city teaching
      hospital.
AB  - Although perinatal HIV prophylaxis is probably the most successful HIV prevention
      intervention to date, between 280 and 370 HIV-positive infants are born in the
      United States each year. A major reason for continuing vertical transmission is
      that some HIV-infected women are not aware of their positive HIV serostatus
      before delivery. A rapid HIV testing program was developed and implemented in a
      labor and delivery suite at an inner-city teaching hospital in a nonresearch
      setting. Between April 2002 and June 2005, 259 rapid HIV tests were performed.
      For the first 19 months of the study, the expedited enzyme-linked immunosorbent
      assay (ELISA) was performed in 62 patients. For the remainder of the study, the
      OraQuick rapid HIV-1 antibody test was performed in 197 patients. Turnaround
      times for the ELISA and OraQuick test were 262 minutes and 143 minutes,
      respectively, a significant difference (P = .002). Four women had positive test
      results. Voluntary rapid HIV testing is a feasible strategy for detection of HIV
      seropositivity in pregnant patients who present in a labor and delivery suite
      with unknown serostatus. This provides an opportunity to administer
      antiretroviral prophylaxis and to incorporate other obstetric interventions to
      decrease vertical HIV transmission.

PMID- 16433471
TI  - Saquinavir/Ritonavir: its evolution and current treatment role.
AB  - As formulations and combinations of drugs to treat HIV infection improve,
      physicians are better able to offer therapies that reduce pill burden while
      maintaining safety and effective viral control. Saquinavir mesylate, the first
      protease inhibitor (PI) approved by the FDA, was recently reformulated to reduce
      pill burden and is meant to be used in regimens boosted with low-dose ritonavir.
      This article reviews ritonavir-enhanced or "boosted" saquinavir regimens and the
      clinical trials using this PI combination and discusses potential advantages of
      and opportunities with the current use of these regimens.

PMID- 16433472
TI  - Adverse reactions associated with dapsone therapy in HIV-positive patients: a
      case presentation and review.
AB  - Dapsone is commonly used for the prophylaxis of Pneumocystis jiroveci pneumonia
      in patients with a diagnosis of HIV infection who have allergies to sulfa-based
      drugs. Dapsone has several adverse effects in its profile that make it a
      potentially dangerous second-line agent. We report an adverse effect encountered
      in an HIV-positive patient receiving dapsone and review the common adverse
      effects encountered with this alternative treatment option.

PMID- 16433473
TI  - [HIV patient hospitalization during the pre and post-HAART era].
AB  - HIV patient hospitalization during the pre and post-HAART era. The purpose of
      this study was to describe and to compare the characteristics of patient
      admissions during two periods, one pre HAART and the other when HAART was fully
      available. A retrospective analysis of demographic data, ambulatory care
      information and hospitalization characteristics was performed. Causes of
      admission, outcome, mortality, length of hospitalization and type of
      antiretroviral therapy were analyzed. A total of 330 medical records were
      reviewed, corresponding to 522 admissions during both study periods: 1995-96 (n =
      289) and 2001-02 (n = 233). The most frequent causes of hospitalization were AIDS
      defining events (period 1: 57.1%; period 2: 59.7%). Tuberculosis was the main
      cause of admission in both periods (23.9% and 15.5%). Criptococosis (3.5%-7.3%),
      Pneumocystis jiroveci pneumonia (5.9%-9.4%), and CNS toxoplasmosis (6.9 -8.6%)
      followed tuberculosis. Mortality did not vary significantly (13.5%-16.1%). HIV-1
      infection was diagnosed at admission in 30% of cases. During 2nd period, a
      significant decrease in re-admission (41.6-26.8%) was observed, whereas there was
      an increase in the percentage of patients with previous antiretroviral treatment
      on admission (8%-25%). An increase in the ambulatory care clinic consultations
      (1995: n = 1678; 1996: n = 2512; 2001: n = 5670; 2002: n = 7074) was observed. No
      significant differences in the causes of admission and outcome in both periods
      were found. Tuberculosis is the most frequent disease that motivates
      hospitalization. The relation between ambulatory consultations and the amount of
      admissions significantly increased.

PMID- 16433474
TI  - [Osteoporosis during pregnancy and lactation. Report of eight cases].
AB  - Both generalized and regional osteoporosis exceptionally occur during pregnancy
      and lactation. The aim of this paper is to show our experience in the diagnosis
      and treatment of these diseases. From 1984 to 2004 six lactating women with
      osteoporosis and two with regional osteoporosis consulted us. In the former
      group, three patients had vertebral fractures and the others experienced
      substantial demineralization detected by dual-energy X-ray absorptiometry (DXA).
      In all cases, symptoms began during the third trimester of pregnancy or
      immediately after delivery. Five of them were primiparous and one was multiparous
      with a long period of lactation. Risk factors were: low calcium intake, low
      weight, family history of osteoporosis, amenorrhea, cigarette consumption and
      corticosteroid therapy. Laboratory tests evidenced increased bone turnover. DXA
      scan showed substantial demineralization, particularly in axial skeleton.
      Lactation was interrupted in all women and four received anti-resorptive drugs,
      one estrogen and only calcium plus vitamin D the remaining. All of them, but one,
      evolved successfully. The women affected by regional osteoporosis complained of
      unilateral pain and progressive functional limitation of right foot and left hip
      respectively. Reduced bone mineral density at symptomatic sites was seen by DXA.
      Diagnosis was confirmed by typical magnetic resonance imaging pattern. Both
      patients cured with rest and bisphosfonates treatment.

PMID- 16433475
TI  - [Risk factors for basal cell carcinoma. Case-control study in Cordoba].
AB  - Basal cell carcinoma is undoubtedly a complex disease. Its etiology is still
      unclear and despite its frequency, there is a paucity of data on its risk
      factors. We assessed potential risk factors for basal cell carcinoma in a
      population from Cordoba (Argentina). This case-control study involved 88 newly
      diagnosed cases and 88 controls, matched by age and sex. The following risk
      factors were significant in the multivariate analysis: skin type I-II-III, high
      recreational sun exposure after 20 years of age, high sun exposure for beach
      holidays and actinic keratosis.

PMID- 16433476
TI  - Predictors of antibiotic prescription in respiratory tract infections by
      ambulatory care practitioners.
AB  - The use of antibiotics in viral respiratory infections (common cold, acute
      rhinosinusitis and acute bronchitis) promotes the emergence and spread of
      resistant bacteria. Studies have found that antibiotics are prescribed for 50-70%
      of respiratory tract infections, despite the fact that most of them have a viral
      etiology. The objective of the study was to determine predictors of antibiotic
      use in acute respiratory infections. It was conducted as a cross-sectional study
      on physicians' practices for antibiotic use. The subjects were internists and
      otolaryngologists of adult patients in an ambulatory setting in Buenos Aires. The
      instrument was a questionnaire with 20 clinical vignettes that included relevant
      variables for making decisions regarding antibiotic use in acute respiratory
      infections. The vignettes were constructed with a fractional factorial design
      with nine clinical variables. The absolute and relative weight of each clinical
      variable that predicted antibiotic use were calculated for each individual
      practitioner using multiple linear regression. The predictors with the greatest
      absolute weight in the decision to prescribe antibiotics were nasal discharge and
      cough (24% and 21% of total weight). The correlation between predictors and
      individual physician answers was high (r2 = 0.73). The mean probability and the
      rate of antibiotic prescription were both about 50%. Predictors of antibiotic use
      for acute respiratory infections among ambulatory physicians in this sample
      differ from internationally accepted guidelines. The likelihood of prescribing
      antibiotics for these illnesses is high. Wider implementation of management
      guidelines for acute respiratory infections could improve cost effective
      antibiotic use and decrease the development of antibiotic resistance.

PMID- 16433477
TI  - Decrease of blood pressure by community-based strategies.
AB  - In a cross section study performed in Rauch in 1997 we found a high prevalence of
      hypertension and low levels of treatment and control. To evaluate the impact of
      the community-based intervention activities on blood pressure (BP), we made a
      cohort study in 1526 inhabitants aged between 15 and 75 years in 2003. The
      initial study, the advice to consult the family doctor when alterations were
      found, the free provision of antihypertensive drugs, the press diffusion of the
      study results and a healthy lifestyle were included among the intervention
      activities. BP was measured in the subjects' residence by especially trained
      nurses, considering systolic BP (SBP) and diastolic BP (DBP) as the average of
      three measurements in one occasion. A total of 1307 subjects (85.65%) were re
      interviewed. SBP decreased from 137.98 +/- 0.57 to 132.49 +/- 0.53 mm Hg (p <
      0.01) and DBP from 88.73 +/- 0.38 to 81.87 +/- 0.33 mm Hg (p < 0.01). Pressure
      decrease was observed in all the age groups, in both sexes and in the subgroup
      without receiving antihypertensive drugs. The percentage with antihypertensive
      drugs increased from 12.2 to 20.4 (p < 0.01). A significant relationship was
      observed between the percentiles of the BP changes and weight changes in subjects
      with and without antihypertensive drugs. Community-based intervention strategies
      were effective to BP control and, probably, to decrease the cardiovascular risk
      in a community with high prevalence of hypertension.

PMID- 16433478
TI  - [Hyperhomocysteinemia as a vascular risk factor in chronic hemodialysis
      patients].
AB  - Homocysteine is an independent risk factor for cardiovascular disease in the
      general population. In addition, it plays a main role in the development of
      atherogenesis and thrombosis, particularly in end-stage renal disease patients.
      Therefore, hemodialysis patients are under the burden of homocysteine toxic
      effects, present in nearly 90% of dialysis patients. Our group found that folic
      acid is an efficient therapeutic approach to decrease homocysteine levels, and
      the addition of intravenous methylcobalamin potentiates this effect; however,
      methylcobalamin alone was unsuccessful to normalize homocysteine levels. With
      time a group of patients required a higher dose of folic acid to reduce
      hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous,
      to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR)
      presented a reduced catalytic activity and required a higher folic acid dose.
      Vascular-access thrombotic events were similar in all patients according to the
      variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key
      to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally
      acompanying malnourishment, is associated to higher mortality. Albeit hyper
      homocysteinemia is considered a vascular risk factor in renal failure patients,
      it has not yet been established in this population if its correction is
      associated with a decrease in the rate of vascular disease and thrombosis.
      However, given the mentioned evidence about the low risk and good tolerance of
      vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine
      blood levels in chronic renal patients and start a prompt treatment, which may
      proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.

PMID- 16433479
TI  - [A 12-week physical activity program increases glucose-6-phosphate-dehydrogenase
      activity in Down syndrome adolescents].
AB  - In recent years it has been claimed that trisomic cells are more sensitive to
      oxidative stress since there is an imbalance in the hydrogen peroxide metabolism.
      We designed the present study to assess the activity level of antioxidant enzyme
      glucose-6-phosphate-dehydrogenase (G6PDH) of erythrocytes in 31 male adolescents
      with Down syndrome (mean age 16.3 +/- 1.1) after performing a 12 week aerobic
      training program. First of all, a significant increase of 14.9% in the catalytic
      activity of G6PDH was observed in male adolescents with Down syndrome when
      compared with age, sex and body mass-matched controls without trisomy. After 12
      wk program its activity increased significantly compared to baseline value in
      Down syndrome individuals. Our data are consistent with previous evidence of the
      existence of higher oxidative stress in adolescents with Down syndrome when
      compared to the general population. We may also conclude that G6PDH activity was
      significantly increased after a 12 week exercise program.

PMID- 16433480
TI  - [Bronchiectasis, pulmonary abcess and clubbing].

PMID- 16433481
TI  - [Histoplasmosis in immunocompetent patient].

PMID- 16433482
TI  - [Merkel cell carcinoma with cutaneous and lymph node metastases].

PMID- 16433483
TI  - [Hemolytic uremic syndrome. Treatment of secondary glomerulopathy].
AB  - Chronic renal failure (CRF) is the most severe complication of hemolytic uremic
      syndrome (HUS). In 1996, the histological sequence of changes in patients with
      long lasting oligoanuric periods was clarified. In the last years different
      therapeutic schemes have been proposed in order to slacken the development of
      terminal CRF in different renal conditions secondary to diabetes and other
      diseases. Some of these cases can suffer the onset of renal failure at
      adolescence. In this review, response to two treatment schemes in different
      patients with HUS and proteinuria with or without hypertension or renal failure
      is commented. Early indication of poor sodium diet and strict control of protein
      intake at the very moment of hospital discharge is strongly recommended, as well
      as angiotensin II conversion inhibiting enzymes (iACE) at the appearance of
      proteinuria.

PMID- 16433484
TI  - [Osteoporosis during pregnancy and lactation].
AB  - During pregnancy and lactation women have to form and maintain fetus and newborn
      skeleton. These processes require maternal hormonal and metabolic adjustments.
      During the first weeks of pregnancy, calcium intestinal absorption rise and reach
      a maximum in the last trimester. Hypercalciuria can be detected until lactation
      is stopped. During lactation, calcium that is present in maternal milk, results
      from lowering maternal calcium excretion and increasing bone resorption. Plasma
      1,25 (OH)(2) D(3) levels increase two-fold early in pregnancy due to high
      placental 1-alpha-hydroxilase activity, remain high until delivery and decline to
      normal values during lactation. Estrogen, prolactin and placental lactogen, which
      are involved in calcium absorption, increase at the same time. Normal or even low
      levels of parathyroid hormone (PTH) can be detected during pregnancy. This
      suggests that their physiological actions could be mimicked by the parathyroid-
      related-peptide (PTHrP), which increases in late stages of pregnancy and remain
      high during delivery and lactation. Calcitonin levels increase during pregnancy,
      decline during lactation and return to normal values after lactation is stopped.
      The physiological roll of tumor necrosis factor, interleukin 6 and
      osteoprotegerin has not been elucidated yet. The above mentioned changes can
      exceptionally lead to generalized or regional osteoporosis. The aim of this
      article is to review the published bibliography concerning the physiopathology of
      these diseases.

PMID- 16433485
TI  - [Three Argentine Nobel Prizes].

PMID- 16433486
TI  - [Environmental tobacco smoke].

PMID- 16433488
TI  - [Quousque tandem? Self administered treatment in tuberculosis].

PMID- 16433487
TI  - [Why should smoking be forbidden in the workplace?].

PMID- 16433489
TI  - [Cecilia Grierson (1859-1934)].

PMID- 16433490
TI  - [Questioning the Self/Non-Self immunology dogma].

PMID- 16433491
TI  - [Santiago Ramon y Cajal. An anniversary].

PMID- 16433492
TI  - [Adult medical orientation. Ambulatory assistance with risk factor stratification
      in a high complexity public hospital].

PMID- 16433493
TI  - Selectivity limitations in the heterogeneous epoxidation of olefins: branching
      reactions of the oxametallacycle intermediate in the partial oxidation of
      styrene.
AB  - The partial oxidation of olefins on Ag surfaces has been a long standing problem
      in surface science and is of great commercial interest. We present a temperature
      programmed reaction spectroscopy (TPRS) and X-ray photoelectron spectroscopy
      (XPS) study of the partial oxidation of styrene on Ag(111). The reaction products
      are CO2, water, styrene oxide, benzene, and benzoic acid. XPS gives evidence for
      two different reaction intermediates that we assign to an oxametallacycle and to
      benzoate. The oxametallacycle seems to be the precursor for both the formation of
      styrene oxide and the formation of benzoate, and thus, in addition to leading to
      styrene oxide, also leads to undesired byproducts. The benzoate reacts further to
      form CO2, benzene, and benzoic acid.

PMID- 16433494
TI  - C. fumago chloroperoxidase is also a dehaloperoxidase: oxidative dehalogenation
      of halophenols.
AB  - We have examined the H2O2-dependent oxidative dehalogenation of 2,4,6
      trihalophenols and p-halophenols catalyzed by Caldariomyces fumago
      chloroperoxidase (CCPO). CCPO is significantly more robust than other peroxidases
      and can function under harsher reaction conditions, and so its ability to
      dehalogenate halophenols could lead to its use as a bioremediation catalyst for
      aromatic dehalogenation reactions. Optimal catalysis occurred under acidic
      conditions (100 mM potassium phosphate solution, pH 3.0). UV-visible absorption
      spectroscopy, high-performance liquid chromatography, and gas chromatography/mass
      spectrometry clearly identified the oxidized reaction product for CCPO-catalyzed
      dehalogenation of 2,4,6-trihalophenols as the corresponding 2,6-dihalo-1,4
      benzoquinones. This reaction has previously been reported for two His-ligated
      heme-containing peroxidases (see Osborne, R. L.; Taylor, L. O.; Han, K. P.; Ely,
      B.; Dawson, J. H. Biochem. Biophys. Res. Commun. 2004, 324, 1194-1198), but this
      is the first example of a Cys-ligated heme-containing peroxidase functioning as a
      dehaloperoxidase. The relative catalytic efficiency (turnover number) of CCPO
      reported herein is comparable to that of horseradish peroxidase (Ferrari, R. P.;
      Laurenti, E.; Trotta, F. J. Biol. Inorg. Chem. 1965, 4, 232-237). The mechanism
      of dehalogenation has been probed using p-halophenols as substrates. Here the
      major product is a dimer with 1,4-benzoquinone as the minor product. An electron
      transfer mechanism is proposed that accounts for the products formed from both
      the 2,4,6-trihalo- and p-halophenols. Finally, we note that this is the first
      case of a peroxidase known primarily for its halogenation ability being shown to
      also dehalogenate substrates.

PMID- 16433495
TI  - Lewis base activation of Lewis acids. Vinylogous aldol addition reactions of
      conjugated N,O-silyl ketene acetals to aldehydes.
AB  - N,O-Silyl dienyl ketene acetals derived from unsaturated morpholine amides have
      been developed as highly useful reagents for vinylogous aldol addition reactions.
      In the presence of SiCl4 and the catalytic action of chiral phosphoramide (R,R)
      3, N,O-silyl dienyl ketene acetal 8 undergoes high-yielding and highly site
      selective addition to a wide variety of aldehydes with excellent
      enantioselectivity. Of particular note is the high yields and selectivities
      obtained from aliphatic aldehydes. Low catalyst loadings (2-5 mol %) can be
      employed. The morpholine amide serves as a useful precursor for further synthetic
      manipulation.

PMID- 16433496
TI  - Direct asymmetric anti-Mannich-type reactions catalyzed by a designed amino acid.
AB  - The development of catalysts for Mannich-type reactions that afford anti-products
      with excellent diastereo- and enantioselectivities under mild conditions and low
      catalyst loadings (1-5 mol %) is reported. Based on principles gained from the
      study of (S)-proline-catalyzed Mannich-type reactions that afford
      enantiomerically enriched syn-products, (3R,5R)-5-methyl-3-pyrrolidinecarboxylic
      acid (RR35) has been designed to catalyze the direct enantioselective anti
      selective Mannich-type reactions. Computational studies of the above reaction
      using HF/6-31G* level of theory suggested that this design would be highly
      effective. The catalyst was subsequently synthesized and studied in
      organocatalytic Mannich-type reactions between unmodified aldehydes and N-PMP
      protected alpha-imino esters. In accord with the design principles and in
      quantitative agreement with the theoretical predictions, reactions catalyzed by
      this catalyst afforded anti-products in good yields with excellent diastereo- and
      enantioselectivities (anti:syn 94:6 to 98:2, >97 to >99% ee).

PMID- 16433497
TI  - Enhanced magnetic properties of self-assembled FePt nanoparticles with MnO shell.
AB  - Self-assembled FePt/MnO nanoparticles with different morphology and size were
      synthesized with a polyol process. With the MnO coating, FePt nanoparticles
      exhibit a high blocking temperature and magnetic moment. The low-temperature
      hysteresis loop of FePt nanoparticles can be shifted through the AFM pinning of
      the MnO shell. The aggregation of FePt nanoparticles during the L10 phase
      transformation can be significantly decreased by coating with the MnO shell.

PMID- 16433498
TI  - An efficient catalyst system for the asymmetric transfer hydrogenation of
      ketones: remarkably broad substrate scope.
AB  - A BINOL-derived diphosphonite having a xanthene backbone is an excellent
      bidentate ligand in Ru-catalyzed 2-propanol-based transfer hydrogenation of
      aryl/alkyl and alkyl/alkyl ketones (ee = 76-99%). Even notoriously difficult
      ketones such as isopropyl methyl ketone are reduced with extraordinarily high
      enantioselectivity (ee = 99%).

PMID- 16433499
TI  - Directed assembly of carbon nanotubes at liquid-liquid interfaces: nanoscale
      conveyors for interfacial biocatalysis.
AB  - We report that single-walled carbon nanotubes (SWNTs) can be directed to aqueous
      organic interfaces with the aid of surfactants. This phenomenon can also be used
      to transport enzymes to the interface to effect biphasic biotransformations.
      Consequently, SWNT-enzyme conjugates enhance the rate of catalysis by up to 3
      orders of magnitude relative to the rates obtained with native enzymes in similar
      biphasic systems. Furthermore, we demonstrate that this concept can be extended
      to other nanomaterials and other enzymes, thereby providing a general strategy
      for efficient interfacial biocatalysis. The ability to direct the assembly of
      nanotubes at the interface also provides an attractive route to organizing these
      nanomaterials into 2D architectures.

PMID- 16433500
TI  - Total synthesis of garsubellin A.
AB  - A concise approach to the laboratory synthesis of garsubellin A is described.
      Garsubellin A, an effective inducer of choline acetyltransferase (ChAT), has been
      shown to have potential as a therapeutic agent for the treatment of Alzheimer's
      disease. Starting from 3,5-dimethoxyphenol, the synthesis has provided
      garsubellin A in an 18-step sequence. Notable transformations include dearomative
      allylation, diastereoselective vinylogous lactonization, iodocarbocyclization,
      transannular Wurtz, and bridgehead functionalization reactions.

PMID- 16433501
TI  - A stable neutral stannaaromatic compound: synthesis, structure and complexation
      of a kinetically stabilized 2-stannanaphthalene.
AB  - A kinetically stabilized 2-stannanaphthalene, the first example of a stable,
      neutral aromatic compound containing a tin atom, has been synthesized and fully
      characterized. The results of spectroscopic and crystallographic structural
      analyses of the compound and theoretical calculations using model compounds
      strongly suggest that it has a delocalized 10pi-electron ring system as does
      naphthalene. In addition, it was found to behave as an eta6-arene ligand in the
      ligand exchange reaction with [Cr(CH3CN)3(CO)3] giving the first stable eta6-2
      stannanaphthalene chromium complex.

PMID- 16433502
TI  - Multiwall carbon nanotubes made of monochirality graphite shells.
AB  - A multiwall carbon nanotube (MWCNT) consists of several or many concentric carbon
      shells, each of which could be metallic or semiconducting. Both theoretical
      predictions and experimental results suggest that MWCNTs have exotic electronic
      structures and intriguing transport properties, which are highly dependent on
      chirality of each shell. However, the structural defects and the random
      distribution of chirality of each concentric graphitic shell make the MWCNTs
      difficult for basic research and technological applications. Thus far, it is
      still a challenge to get the high crystalline MWCNTs with limited atomic
      conformation. Here, we report the synthesis of high crystalline MWCNTs made of
      monochirality graphite shells by a low-temperature chemical vapor deposition
      (CVD) process in plasma environment. Structural analysis, carried out by
      transmission electron microscopy (TEM) image and electron diffraction methods,
      reveal that the MWCNTs are well-crystallized and that most of them have nearly
      identical chiralities.

PMID- 16433503
TI  - Rapid synthesis of high-quality InP nanocrystals.
AB  - A rapid new method for preparation of monodisperse InP-nanocrystals was
      developed. A highly reactive indium precursor and tris(trimethylsilyl)phosphine
      (TMS)3P was reacted within a weakly coordinating solvent in the presence of a
      supporting protic agent. The yielded InP-nanocrystals had a very narrow size
      distribution without any size selection process. The precursor and ligand effects
      were considered as critical factors in control of nucleation and crystal growth
      process. Different ligands were introduced to study the reaction mechanism. The
      new method not only yielded the "best" InP-nanocrystals so far, but also includes
      the potential for preparation within a continuous flow reactor, because the
      utilized ester is liquid at room temperature.

PMID- 16433504
TI  - Ladder polyether synthesis via epoxide-opening cascades using a disappearing
      directing group.
AB  - The combination of a trimethylsilyl group, a Bronsted base, a fluoride source,
      and a hydroxylic solvent enables the first construction of the tetrad of
      tetrahydropyran rings found in the majority of the ladder polyether natural
      products by way of a cascade of epoxide-opening events that emulates the final
      step of Nakanishi's proposed biosynthetic pathway. The trimethylsilyl group
      disappears during the course of the cascade, and thus these are the first epoxide
      ring-opening cascades that afford ladder polyether subunits containing no
      directing groups at the end of the cascade.

PMID- 16433505
TI  - The Neber route to substituted indoles.
AB  - Two complementary procedures have been developed for the conversion of the oximes
      of alpha-aryl ketones to azirines. On heating, the azirines rearrange smoothly to
      the corresponding indoles. The overall transformation offers a versatile route to
      indoles, complementary to the Fischer indole synthesis.

PMID- 16433506
TI  - C-H activation as a strategic reaction: enantioselective synthesis of 4
      substituted indoles.
AB  - A method is described for the asymmetric synthesis of 4-substituted indoles from
      the Rh2(S-DOSP)4-catalyzed decomposition of vinyldiazoacetates in the presence of
      N-Boc-4-acetoxy-6,7-dihydroindole. The reaction proceeds via a combined C-H
      activation/Cope rearrangement-elimination mechanism resulting in good yields and
      very high asymmetric induction.

PMID- 16433507
TI  - Synthesis of tetrasubstituted and functionalized enol ethers by E-selective
      olefination of esters with ynolates.
AB  - We have developed the E-selective olefination of ester carbonyls to afford
      tetrasubstituted, functionalized olefins and the C-S insertion of thiol esters to
      give beta-keto thiol esters via ynolates.

PMID- 16433508
TI  - Biomimetic surface modifications based on the cyanobacterial iron chelator
      anachelin.
AB  - Siderophores are natural iron chelators that have been evolutionarily selected to
      bind to Fe ions with very high binding constants. We utilize these unique
      properties to bind to metal oxide surfaces using a fragment of the cyanobacterial
      siderophore anachelin. The resulting poly(ethylene glycol) conjugate forms stable
      adlayers on TiO2 as has been shown by variable angle spectroscopic ellipsometry
      and X-ray photoelectron spectroscopy. Moreover, these coated surfaces are highly
      protein-resistant against the adsorption of full human serum.

PMID- 16433509
TI  - Proton abstraction mechanism for the palladium-catalyzed intramolecular
      arylation.
AB  - Under the usual conditions, the Pd-catalyzed arylation does not involve an
      electrophilic aromatic substitution reaction. On the basis of DFT calculations,
      we propose a mechanism for the Pd-catalyzed arylation that involves a proton
      abstraction by a carbonate or related ligand and that provides a satisfactory
      explanation for the experimental data.

PMID- 16433510
TI  - Ultrafast excited-state electron transfer at an organic liquid/aqueous interface.
AB  - Ultrafast excited-state electron transfer has been monitored at the liquid/liquid
      interface for the first time. Second harmonic generation (SHG) pump/probe
      measurements monitored the electron transfer (ET) occurring between photoexcited
      coumarin 314 (C314) acceptor and dimethylaniline (DMA) donor molecules. In the
      treatment of this problem, translational diffusion of solute molecules can be
      neglected since the donor DMA is one of the liquid phases of the interface. The
      dynamics of excited-state C314 at early times are characterized by two components
      with exponential time constants of 362 +/- 60 fs and 14 +/- 2 ps. The 362 fs
      decay is attributed to the solvation of the excited-state C314, and the 14 ps to
      the ET from donor to acceptor. We are able to provide conclusive evidence that
      the 14 ps component is the ET step by monitoring the formation of the radical DMA
      cation. The formation time is 16 ps in agreement with the 14 ps decay of C314*.
      The recombination dynamics of DMA+ plus C314- was determined to be 163 ps from
      the observation of the DMA+ SHG signal.

PMID- 16433511
TI  - Enzyme-triggered self-assembly of peptide hydrogels via reversed hydrolysis.
AB  - We demonstrate that proteases can be used to selectively trigger the self
      assembly of peptide hydrogels via reversed hydrolysis.

PMID- 16433512
TI  - Nonlinear optical properties of alkalides Li+(calix[4]pyrrole)M- (M = Li, Na, and
      K): alkali anion atomic number dependence.
AB  - A new type of alkalide compound, Li+(calix[4]pyrrole)M- (M = Li, Na, and K), is
      presented in theory, which may be stable at room temperature. It has been shown
      by our calculations that the first hyperpolarizability (beta) is considerably
      large by means of the density functional theory method. The beta values are
      determined at the B3LYP/6-311++G level (for the alkali atoms the 6-311++G(3df)
      basis set is employed) as 8.9 x 103, 1.0 x 104, and 2.4 x 104 au for M = Li, Na,
      and K, respectively. These beta values are much larger than that of electride
      Li+(calix[4]pyrrole)e- (beta = 7.3 x 103 au) by a factor of 1.2 to 3.4. Comparing
      to the cryptand calix[4]pyrrole, the beta values of Li+(calix[4]pyrrole)M- are
      enhanced by 20-60 times. It is revealed, for the first time, that the beta value
      of alkalide compounds depends on the atomic number of the alkali anion, and it
      can be enhanced by choosing the akali anions with larger atomic numbers. The
      alkali anion in the alkalide compound decreases the transition energy and also
      increases the oscillator strength of the main transition, consequently the beta
      value is enhanced. This study proposes such a novel way to synthesize and design
      new NLO materials by using the alkali atom with a larger atomic number to create
      an anion in alkalide compounds.

PMID- 16433513
TI  - Thermal and UV shape shifting of surface topography.
AB  - The confinement of LCE materials into surface monodomains via micropatterning
      leads to the formation of reversible, shape-shifting surface patterns. The
      individual features are liquid crystalline monodomains, and by switching to an
      isotropic state using light or heat, the features switch between imprinted
      circular features and anisotropic liquid crystalline features.

PMID- 16433514
TI  - Enantiospecific adsorption of cysteine at chiral kink sites on Au(110)-(1 x 2).
AB  - Enantiospecific adsorption of cysteine molecules onto chiral kink sites on the
      Au(110)-(1x2) surface was observed by scanning tunneling microscopy. l- and d
      cysteine dimers were found to adopt distinctly different adsorption geometries at
      S kinks, which can be understood from the need to reach specific, optimum
      molecule-substrate interaction points. Extended, homochiral domains of l/d
      cysteine were furthermore observed to grow preferentially from R/S kinks. The
      results constitute the first direct, microscopic observation of enantiospecific
      molecular interaction with chiral sites on a metal single-crystal surface.

PMID- 16433515
TI  - Glutathione-mediated delivery and release using monolayer protected nanoparticle
      carriers.
AB  - We demonstrate here the effective delivery of a dye payload into cells using 2-nm
      core gold nanoparticles, with release occurring via place exchange of glutathione
      onto the particle surface. In vitro experiments demonstrate effective release of
      drug analogues upon addition of glutathione. Cell culture experiments show rapid
      uptake of nanoparticle and effective release of payload. The role of glutathione
      in the release process was demonstrated through improved payload release upon
      transient increase in glutathione levels achieved via introduction of glutathione
      ethyl ester into the cell.

PMID- 16433516
TI  - Tyrosine-selective protein alkylation using pi-allylpalladium complexes.
AB  - A new protein modification reaction has been developed based on a palladium
      catalyzed allylic alkylation of tyrosine residues. This technique employs
      electrophilic pi-allyl intermediates derived from allylic acetate and carbamate
      precursors and can be used to modify proteins in aqueous solution at room
      temperature. To facilitate the detection of modified proteins using SDS-PAGE
      analysis, a fluorescent allyl acetate was synthesized and coupled to
      chymotrypsinogen A and bacteriophage MS2. The tyrosine selectivity of the
      reaction was confirmed through trypsin digest analysis. The utility of the
      reaction was demonstrated by using taurine-derived carbamates as water
      solubilizing groups that are cleaved upon protein functionalization. This
      solubility switching technique was used to install hydrophobic farnesyl and C(17)
      chains on chymotrypsinogen A in water using little or no cosolvent. Following
      this, the C(17) alkylated proteins were found to associate with lipid vesicles.
      In addition to providing a new protein modification strategy targeting an under
      utilized amino acid side chain, this method provides convenient access to
      synthetic lipoproteins.

PMID- 16433517
TI  - An unprecedented type of linear metallocene with an f-element.
AB  - The dication [(C5Me5)2U(NCMe)5]2+ was obtained by dissolving (C5Me5)2UI2 in
      acetonitrile or by treating (C5Me5)2UMe2 with HNEt3BPh4 in acetonitrile. The
      crystal structure revealed that the cyclopentadienyl rings are parallel and
      equidistant to the plane defined by the metal center and nitrogen atoms of the
      five MeCN ligands. Fifty years after the discovery of ferrocene, this compound
      represents a unique example of linear metallocene with auxiliary ligands in the
      equatorial girdle; it is also the first linear sandwich complex of an f-element.

PMID- 16433518
TI  - Coordination bond formation at charge-transfer phase transition in
      (BDTA)2[Co(mnt)2].
AB  - The crystal structure of a charge-transfer salt, (BDTA)2[Co(mnt)2], where BDTA is
      1,3,2-benzodithiazolyl and mnt is maleonitriledithiolate, consisted of an
      alternating stacking column of a head-to-head BDTA+ dimer and a planar
      [Co(mnt)2]2- dianion at 253 K. Magnetic measurements and structural analyses
      revealed a phase transition at 190 K, where a partial electron transfer occurred
      from [Co(mnt)2]2- to one of the BDTA+ cations, forming a coordination bond
      between the two.

PMID- 16433519
TI  - Catalytic asymmetric Pictet-Spengler reaction.
AB  - A catalytic asymmetric Pictet-Spengler reaction has been developed, wherein
      treating substituted tryptamines with an aldehyde in the presence of a catalytic
      amount of a chiral phosphoric acid provides the corresponding tetrahydro-beta
      carboline derivatives in high yields and enantiomeric excesses. The reaction
      works well with both aliphatic and aromatic aldehydes.

PMID- 16433520
TI  - Micro-actuators: when artificial muscles made of nematic liquid crystal
      elastomers meet soft lithography.
AB  - The production, via soft lithography, of micron-sized thermoresponsive pillars
      made of side-on nematic LCE leads to the formation of surface-responsive
      structures. The individual, monodisperse pillars, when cut out from the surface,
      behave as micro-actuators, showing contraction of around 35% at the nematic to
      isotropic phase transition.

PMID- 16433521
TI  - Compound I of heme oxygenase cannot hydroxylate its heme meso-carbon.
AB  - Heme oxygenase (HO) catalyzes heme catabolism through three successive
      oxygenation steps where the substrate heme itself activates O2. It has been
      thought that the reactive species responsible for the first heme oxygenation,
      meso-hydroxylation, is the hydroperoxy-ferric heme intermediate (Fe-OOH) rather
      than an oxo ferryl porphyrin cation radical, so-called compound I. A recent
      theoretical study (Kamachi, T.; Yoshizawa, K. J. Am. Chem. Soc. 2005, 127,
      10686), however, proposed that compound I can oxidize its meso-carbon atom with
      the assistance of a bridging water molecule. In this communication, we report the
      first direct observation of compound I of a heme-HO-1 complex, generated by
      reaction of ferric-HO-1 with m-chloroperbenzoic acid. HO compound I slowly decays
      to compound II without producing any meso-hydroxylated products. It does react
      with guaiacol and thioanisole, however. Our findings unambiguously rule out
      involvement of compound I in the HO catalysis.

PMID- 16433522
TI  - A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design,
      synthesis, and in vitro and in vivo evaluation.
AB  - Protein arginine deiminase 4 (PAD4) is a calcium-dependent transcriptional
      corepressor that has been implicated in the onset and progression of rheumatoid
      arthritis. Herein we describe the synthesis and in vitro evaluation of a
      fluoroacetamidine-containing compound, N-alpha-benzoyl-N5-(2-fluoro-1-iminoethyl)
      l-ornithine amide, 1, hereafter referred to as F-amidine, that is the most potent
      PAD4 inhibitor ever described. Additional studies described herein indicate that
      F-amidine can also inhibit PAD4 activity in vivo. The bioavailability of this
      compound suggests that F-amidine will be a powerful chemical probe of PAD4
      function that can be used to dissect the roles of this enzyme in both rheumatoid
      arthritis and transcriptional control. The fact that inhibition is of an
      irreversible nature suggests that, with appropriate functionalization, F-amidine
      analogues will be robust activity-based protein-profiling and proteomic capture
      reagents.

PMID- 16433523
TI  - Total synthesis of (+)-cylindramide A.
AB  - A total synthesis of cylindramide A has been completed in 19 steps. The key step
      of the synthesis is a tandem ring-opening-ring-closing-cross metathesis that
      converts a readily available norbornene into an advanced intermediate.

PMID- 16433524
TI  - An intramolecular G-quadruplex structure with mixed parallel/antiparallel G
      strands formed in the human BCL-2 promoter region in solution.
AB  - We report the first G-quadruplex structure formed in the promoter region of the
      human bcl-2. Bcl-2 is a potent oncoprotein that functions as an inhibitor of cell
      apoptosis and has been found to be aberrantly overexpressed in a wide range of
      human tumors. A highly GC-rich region upstream of the P1 promoter plays an
      important role in the regulation of the transcriptional activity of the bcl-2
      oncogene. The purine-rich strand of this region contains multiple runs of
      guanines and can form three distinct intramolecular G-quadruplexes in K+
      containing solution. Of these, the G-quadruplex formed within the middle four
      consecutive guanine runs has been shown to be the most stable G-quadruplex
      structure, while it is also a mixture of loop isomers. The predominant G
      quadruplex structure formed in this region was studied by NMR. Our results
      demonstrate a novel folding of a unique intramolecular G-quadruplex structure
      with mixed parallel/antiparallel G-strands. This G-quadruplex structure contains
      three G-tetrads connected with a single-nucleotide double-chain-reversal side
      loop and two lateral loops. The first three-nucleotide CGC loop in the bcl-2
      promoter sequence forms a lateral loop, as opposed to a double-chain-reversal
      side loop observed in a similar sequence in the c-MYC promoter, which appears to
      largely determine the overall folding of the bcl-2 G-quadruplex. Furthermore,
      both the bcl-2 and c-MYC promoter sequences contain the G3NG3 sequence motif,
      which forms a stable double-chain-reversal, parallel-stranded structural motif.
      This predominant bcl-2 G-quadruplex represents an attractive novel target for the
      design of new anticancer drugs that specifically modulate bcl-2 gene expression.

PMID- 16433525
TI  - Periodic and high-temperature disordered conformations of polytetrafluoroethylene
      chains: an ab initio modeling.
AB  - We report here the main results of a successful attempt to predict some
      macroscopic properties of representative polymers of technological relevance both
      in regular and disordered forms by using first principle quantum mechanical
      approaches at microscopic level. Until now, the prediction of the structural and
      thermal properties of those polymers has been mostly a domain of molecular
      mechanics methods. To overcome the limits of those classical computational tools
      whenever physical properties are significantly influenced by stereoelectronic
      effects (e.g., electron rich substituents), we employed methods rooted in the
      Density Functional Theory (DFT). A general computational strategy including the
      proper choice of periodic boundary conditions (PBC), functional, basis set, and
      model system size, has been tested and validated for saturated polymers such as
      polyethylene and isotactic/syndiotactic polypropylenes. On the basis of these
      results, a comprehensive study of poly(tetrafluoroethylene) (PTFE) chains in both
      regular periodic and disordered conformations has been performed. A statistical
      approach has been next applied to obtain the thermal concentration of defects and
      to reproduce the thermal behavior of the investigated polymer. At the end, a very
      good agreement with experimental X-ray diffraction and IR results has been
      achieved, definitely reaching a good understanding of the widely studied disorder
      phenomenon determining the main technological properties of
      poly(tetrafluoroethylene) (the trade Teflon) and, at the same time, identifying
      the proper computational tools to investigate perfluoro-compounds and other
      complex polymeric systems.

PMID- 16433526
TI  - Competition between metal-amido and metal-imido chemistries in the alkaline earth
      series: an experimental and theoretical study of BaNH.
AB  - The pure rotational spectrum of BaNH in its X(1)Sigma(+) ground electronic state
      has been recorded using millimeter/submillimeter direct absorption methods; data
      for the deuterium and barium 137 isotopomers have been measured as well. The
      molecules were produced by the reaction of ammonia or ND(3) and barium vapor in
      the presence of a dc discharge. Transitions arising from the ground vibrational
      state and the excited vibrational bending (01(1)0) and heavy atom stretching
      (100) modes were measured. The rotational spectrum indicates a linear structure,
      with B(0)(BaNH) = 7984.549 MHz and B(0)(BaND) = 7060.446 MHz. An r(m)((1))
      structure has been determined, yielding r(BaN) = 2.077 +/- 0.002 Angstroms and
      r(NH) = 1.0116 +/- 0.0006 Angstroms. Density functional calculations using an
      extensive Slater-type basis set with inclusion of scalar relativistic effects
      gives geometrical parameters and vibrational frequencies for BaNH in excellent
      agreement with those determined by experiment. The molecular orbital and natural
      bond order analyses of the BaNH wave function show Ba-N pi bonds formed by
      electron donation from the formally filled N 2p orbitals of the imido group to
      the empty Ba 5d orbitals. The multiple bonding between Ba and N stabilizes the
      linear geometry and, along with the relative ease of oxidation of the Ba atom,
      favors formation of the metal-imido species over that of the metal-amido species
      that have been found from similar studies with Mg, Ca, and Sr atoms in this
      group.

PMID- 16433527
TI  - Temperature-sensitive micrometer-thick layers of hyaluronan grafted on
      microspheres.
AB  - The giant polyelectrolyte glycosaminoglycan hyaluronan (1-10 MDa) is a major
      component of the pericellular coat on a variety of cells, where it is an
      important modulator and mediator of early cell adhesion events. This pericellular
      layer can reach 5 mum thickness on cells that produce cartilage (chondrocytes),
      and up to 2 mum on Xenopus laevis kidney epithelial cells (A6). We are interested
      in generating model systems for the pericellular coat in order to learn more
      about the structure and function of hyaluronan on biological or artificial
      surfaces. We report here the synthesis of model systems where a coat of
      coordinatively cross-linked hyaluronan of up to 2 mum thickness was covalently
      photografted onto polystyrene microspheres. The hydrated coat was imaged directly
      by environmental scanning electron microscopy (ESEM) at close to 100% relative
      humidity. The key feature of the procedure is the reversible reverse-temperature
      phase transition of hyaluronan induced by trivalent lanthanide cations, which is
      exploited to achieve sufficient density for grafting of thick layers. The
      microsphere-grafted coat shows a temperature-dependent swelling when labeled with
      lanthanide ions (Gd(3+) or Tb(3+)). We directly observed a volume contraction of
      20% with increasing temperature between 1 and 11 degrees C by wet-mode ESEM.

PMID- 16433528
TI  - NMR analysis of aromatic interactions in designed peptide beta-hairpins.
AB  - Designed octapeptide beta-hairpins containing a central (D)Pro-Gly segment have
      been used as a scaffold to place the aromatic residues Tyr and Trp at various
      positions on the antiparallel beta-strands. Using a set of five peptide hairpins,
      aromatic interactions have been probed across antiparallel beta-sheets, in the
      non-hydrogen bonding position (Ac-L-Y-V-(D)P-G-L-Y/W-V-OMe: peptides 1 and 2),
      diagonally across the strands (Boc-Y/W-L-V-(D)P-G-W-L-V-OMe: peptides 3 and 6),
      and along the strands at positions i and i + 2 (Boc-L-L-V-(D)P-G-Y-L-W-OMe:
      peptide 4). Two peptides served as controls (Boc-L-L-V-(D)P-G-Y-W-V-OMe: peptide
      5; Boc-L-Y-V-(D)P-G-L-L-V-OMe: peptide 7) for aromatic interactions. All studies
      have been carried out using solution NMR methods in CDCl(3) + 10% DMSO-d(6) and
      have been additionally examined in CD(3)OH for peptides 1 and 2. Inter-ring
      proton-proton nuclear Overhauser effects (NOEs) and upfield shifted aromatic
      proton resonances have provided firm evidence for specific aromatic interactions.
      Calculated NMR structures for peptides 1 and 2, containing aromatic pairs at
      facing non-hydrogen bonded positions, revealed that T-shaped arrangements of the
      interacting pairs of rings are favored, with ring current effects leading to
      extremely upfield chemical shifts and temperature dependences for specific
      aromatic protons. Anomalous far-UV CD spectra appeared to be a characteristic
      feature in peptides where the two aromatic residues are spatially proximal. The
      observation of the close approach of aromatic rings in organic solvents suggests
      that interactions of an electrostatic nature may be favored. This situation may
      be compared to the case of aqueous solutions, where clustering of aromatic
      residues is driven by solvophobic (hydrophobic) forces.

PMID- 16433529
TI  - In situ generation of vinyl allenes and its applications to one-pot assembly of
      cyclohexene, cyclooctadiene, 3,7-nonadienone, and bicyclo[6.4.0]dodecene
      derivatives with palladium-catalyzed multicomponent reactions.
AB  - A novel tandem Pd-catalyzed cross-coupling and [4 + 4] cycloaddition sequence
      allows the rapid synthesis of eight-membered carbocycles starting from alpha
      bromovinyl arenes and propargyl bromides in one reaction vessel. It is noteworthy
      that four components are assembled into one molecule via this procedure. In
      contrast to alpha-bromovinyl arenes, alpha-bromovinyl alkanes afforded tandem
      cross-coupling and homo [4 + 2] cycloaddition products. Subjecting an equimolar
      mixture of alpha-bromostyrene and 2-bromo-1-octene to propargyl bromides
      furnished the tandem Pd-catalyzed cross-coupling and hetero [4 + 2] cycloaddition
      product. Exposure of equimolar mixtures of alpha-bromovinyl arenes to
      allenylindium resulted in tandem a Pd-catalyzed cross-coupling and hetero [4 + 4]
      cycloaddition products. Synthesis of vinylallene from the reaction of vinyl
      triflate with allenylindium followed by Pd-catalyzed carbon monoxide insertion
      reaction gave the corresponding 3,7-nonadienone product via tandem Pd-catalyzed
      cross-coupling and [4 + 4 + 1] annulation. Tandem Pd-catalyzed cross-coupling, [4
      + 4] cycloaddition, and [4 + 2] cycloaddition provided the rapid synthesis of
      bicyclo[6.4.0]dodecene derivatives starting from alpha-bromovinyl arenes,
      propargyl bromides, and dienophiles in one operation, in which five components
      were integrated into one molecule.

PMID- 16433530
TI  - Five-coordinate aluminum bromides: synthesis, structure, cation formation, and
      cleavage of phosphate ester bonds.
AB  - The alkane elimination reaction between Salen((t)Bu)H(2) ligands and
      diethylaluminum bromide was used to prepare three Salen aluminum bromide
      compounds salen((t)Bu)AlBr (1) (salen = N,N'-ethylenebis(3,5-di-tert
      butylsalicylideneimine)), salpen((t)Bu)AlBr (2) (salpen = N,N'-propylenebis(3,5
      di-tert-butylsalicylideneimine)), and salophen((t)Bu)AlBr (3) (salophen = N,N'-o
      phenylenenebis(3,5-di-tert-butylsalicylideneimine)). The compounds contain five
      coordinate aluminum either in a distorted square pyramidal or a trigonal
      bipyramidal environment. The bromide group in these compounds could be displaced
      by triphenylphosphine oxide or triphenyl phosphate to produce the six-coordinate
      cationic aluminum compounds [salen((t)Bu)Al(Ph(3)PO)(2)]Br (4),
      [salpen((t)Bu)Al(Ph(3)PO)(2)]Br (5), [salophen((t)Bu)Al(Ph(3)PO)(2)]Br (6), and
      [salophen((t)Bu)Al[(PhO)(3)PO)](2)]Br (7). All the compounds were characterized
      by (1)H, (13)C, (27)Al, and (31)P NMR, IR, mass spectrometry, and melting point.
      Furthermore, compounds 1-3 and 5-7 were structurally characterized by single
      crystal X-ray diffraction. Compounds 1-3 dealkylated a series of organophosphates
      in stoichiometric reactions by breaking the ester C-O bond. Also, they were
      catalytic in the dealkylation reaction between trimethyl phosphate and added
      boron tribromide.

PMID- 16433531
TI  - Computational design of a single amino acid sequence that can switch between two
      distinct protein folds.
AB  - The functions of many proteins are mediated by specific conformational changes,
      and therefore the ability to design primary sequences capable of secondary and
      tertiary changes is an important step toward the creation of novel functional
      proteins. To this end, we have developed an algorithm that can optimize a single
      amino acid sequence for multiple target structures. The algorithm consists of an
      outer loop, in which sequence space is sampled by a Monte Carlo search with
      simulated annealing, and an inner loop, in which the effect of a given mutation
      is evaluated on the various target structures by using the rotamer packing
      routine and composite energy function of the protein design software,
      RosettaDesign. We have experimentally tested the method by designing a peptide,
      Sw2, which can be switched from a 2Cys-2His zinc finger-like fold to a trimeric
      coiled-coil fold, depending upon the pH or the presence of transition metals.
      Physical characterization of Sw2 confirms that it is able to reversibly adopt
      each intended target fold.

PMID- 16433532
TI  - Helical conformational dynamics and photoisomerism of alternating
      pyridinedicarboxamide/m-(phenylazo)azobenzene oligomers.
AB  - Alternating sequences of pyridine-2,6-dicarboxamides and meta
      (phenylazo)azobenzenes have been assembled into oligomers composed of four (8)
      and eight (9) azobenzene linkages. X-ray crystallography confirmed that oligomer
      8 adopts a two-turn helical conformation with a helical pitch of approximately
      3.4 Angstroms in the solid state. The presence of a two- and four-turn helical
      conformation of 8 and 9, respectively, in polar and nonpolar solvents was
      elucidated by the anisotropic upfield shifting of protons located within the
      helices, NOE enhancements between protons oriented toward the helix interior, and
      the diastereotopicity of the terminal benzyloxycarbonyl (CBz) methylene protons.
      (1)H NMR line shape analysis of the CBz methylene hydrogens at the chain ends
      revealed a dynamic equilibria interconverting M and P helical conformations with
      energetic barriers (DeltaG) of 11.1 (DeltaS = -19.4 +/- 1.6 cal mol(-1) K(-1);
      DeltaH = 6.5 +/- 0.4 kcal/mol) for 8 and 13.8 kcal/mol (DeltaS = -6.6 +/- 6.2 cal
      mol(-1) K(-1); DeltaH = 11.8 +/- 1.8 kcal/mol) for 9. Irradiation of the
      oligomers with 350 nm light induces an E --> Z isomerization of the azo linkages
      that decreases in efficacy at longer helix lengths. The suppression of E --> Z
      isomerization is a consequence of the contrasting behavior of the azo linkages
      located at the helix termini, which afford Z/E ratios similar to those of model
      compound 7d, and the internal azo groups, which undergo significantly lower Z/E
      conversion ratios compared with 7e.

PMID- 16433533
TI  - Kinetic solvent effects on proton and hydrogen atom transfers from phenols.
      Similarities and differences.
AB  - Bimolecular rate constants for proton transfer from six phenols to the anthracene
      radical anion have been determined in up to eight solvents using electrochemical
      techniques. Effects of hydrogen bonding on measured rate constants were explored
      over as wide a range of phenolic hydrogen-bond donor (HBD) and solvent hydrogen
      bond acceptor (HBA) activities as practical. The phenols' values ranged from
      0.261 (2-MeO-phenol) to 0.728 (3,5-Cl(2)-phenol), and the solvents' values from
      0.44 (MeCN) to 1.00 (HMPA), where and are Abraham's parameters describing
      relative HBD and HBA activities (J. Chem. Soc., Perkin Trans. 2 1989, 699; 1990,
      521). Rate constants for H-atom transfer (HAT) in HBA solvents, k(S), are
      extremely well correlated via log k(S) = log k(0) - 8.3 , where k(0) is the rate
      constant in a non-HBA solvent (Snelgrove et al. J. Am. Chem. Soc. 2001, 123,
      469). The same equation describes the general features of proton transfers (k(S)
      decreases as increases, slopes of plots of log k(S) against increase as
      increases). However, in some solvents, k(S) values deviate systematically from
      the least-squares log k(S) versus correlation line (e.g., in THF and MeCN, k(S)
      is always smaller and larger, respectively, than "expected"). These deviations
      are attributed to variations in the solvents' anion solvating abilities (THF and
      MeCN are poor and good anion solvators, respectively). Values of log k(S) for
      proton transfer, but not for HAT, give better correlations with Taft et al.'s (J.
      Org. Chem. 1983, 48, 2877) beta scale of solvent HBA activities than with . The
      beta scale, therefore, does not solely reflect solvents' HBA activities but also
      contains contributions from anion solvation.

PMID- 16433534
TI  - A combined experimental and theoretical study of carboxylate coordination modes:
      a structural probe.
AB  - The variations of the frequency differences of symmetric and asymmetric
      stretching vibrations in a series of carboxylato Fe(II) complexes have been
      theoretically studied. It is shown that structural information can be obtained
      from a direct comparison between the difference (Delta = nu(as) - nu(s)) in the
      asymmetric (nu(as)) and symmetric (nu(s)) carboxylate vibrations of the free
      anion and that of the coordinated species. The coordination mode approaches C(2v)
      symmetry as Delta decreases with respect to its value for the noncoordinated
      carboxylate. The use of IR spectroscopy in the resolution of speculated
      crystallographic structures is suggested.

PMID- 16433535
TI  - Optimization of the molecular orbital energies of conjugated polymers for optical
      amplification of fluorescent sensors.
AB  - Cationic water-soluble poly(fluorene-co-phenylene)s with electron withdrawing or
      donating substituents on the conjugated backbone were designed and synthesized.
      Fluorescence resonance energy transfer (FRET) experiments between these
      conjugated polymers and dye-labeled single-stranded DNA (ssDNA-C*) reveal the
      importance of matching donor and acceptor orbital energy levels to improve the
      sensitization of C* emission. Quenching of polymer fluorescence with ssDNA-C* and
      differences in C* emission suggest involvement of photoinduced charge transfer
      (PCT) as an energy wasting mechanism. The HOMO and LUMO energy levels of the
      conjugated polymers and C serve as a preliminary basis to understand the
      competition between FRET and PCT. Dilution of C in polymer/ssDNA-C complexes by
      addition of ssDNA yields insight into C*...C self-quenching. Under optimized
      conditions, where there is no probe self-quenching and minimum PCT, efficient
      signal amplification is demonstrated despite poor spectral overlap between
      polymer and C.

PMID- 16433536
TI  - Effect of silicon oxidation on long-term cell selectivity of cell-patterned
      Au/SiO2 platforms.
AB  - Cellular patterning on silicon platforms is the basis for development of
      integrated cell-based biosensing devices, for which long-term cell selectivity
      and biostability remain a major challenge. We report the development of a silicon
      based platform in a metal-insulator format capable of producing uniform and
      biostable cell patterns with long-term cell selectivity. Substrates patterned
      with arrays of gold electrodes were surface-engineered such that the electrodes
      were activated with fibronectin to mediate cell attachment and the silicon oxide
      background was passivated with PEG to resist protein adsorption and cell
      adhesion. Three types of oxide surfaces, i.e., native oxide, dry thermally grown
      oxide, and wet thermally grown oxide, were produced to illustrate the effect of
      oxide state of the surface on long-term cell selectivity. Results indicated that
      the cell selectivity over time differed dramatically among three patterned
      platforms and the best cell selectivity was found on the dry oxide surface for up
      to 10 days. Surface analysis results suggested that this enhancement in cell
      selectivity may be related to the presence of additional, more active oxide
      states on the dry oxide surface supporting the stability of PEG films and
      effectively suppressing the cell adhesion. This research offers a new strategy
      for development of stable and uniform cell-patterned surfaces, which is versatile
      for immobilization of silane-based chemicals for preparation of biostable
      interfaces.

PMID- 16433538
TI  - Ultrafast fluorescence dynamics of tryptophan in the proteins monellin and
      IIAGlc.
AB  - The complete time-resolved fluorescence of tryptophan in the proteins monellin
      and IIA(Glc) has been investigated, using both an upconversion
      spectrophotofluorometer with 150 fs time resolution and a time-correlated single
      photon counting apparatus on the 100 ps to 20 ns time scale. In monellin, the
      fluorescence decay displays multiexponential character with decay times of 1.2
      and 16 ps, and 0.6, 2.2, and 4.2 ns. In contrast, IIA(Glc) exhibited no component
      between 1.2 ps and 0.1 ns. For monellin, surprisingly, the 16 ps fluorescence
      component was found to have positive amplitude even at longer wavelengths (e.g.,
      400 nm). In conjunction with quantum mechanical simulation of tryptophan in
      monellin, the experimental decay associated spectra (DAS) and time-resolved
      emission spectra (TRES) indicate that this fluorescence decay time should be
      ascribed to a highly quenched conformer. Recent models (Peon, J.; et al. Proc.
      Natl.Acad. Sci. U.S.A. 2002, 99, 10964) invoked exchange-coupled relaxation of
      protein water to explain the fluorescence decay of monellin.

PMID- 16433537
TI  - A localized specific interaction alters the unfolding pathways of structural
      homologues.
AB  - Reductive unfolding studies of proteins are designed to provide information about
      intramolecular interactions that govern the formation (and stabilization) of the
      native state and about folding/unfolding pathways. By mutating Tyr92 to G, A, or
      L in the model protein, bovine pancreatic ribonuclease A, and through analysis of
      temperature factors and molecular dynamics simulations of the crystal structures
      of these mutants, it is demonstrated that the markedly different reductive
      unfolding rates and pathways of ribonuclease A and its structural homologue
      onconase can be attributed to a single, localized, ring-stacking interaction
      between Tyr92 and Pro93 in the bovine variant. The fortuitous location of this
      specific stabilizing interaction in a disulfide-bond-containing loop region of
      ribonuclease A results in the localized modulation of protein dynamics that, in
      turn, enhances the susceptibility of the disulfide bond to reduction leading to
      an alteration in the reductive unfolding behavior of the homologues. These
      results have important implications for folding studies involving topological
      determinants to obtain folding/unfolding rates and pathways, for protein
      structure-function prediction through fold recognition, and for predicting
      proteolytic cleavage sites.

PMID- 16433539
TI  - A structural investigation of the N-B interaction in an o-(N,N
      dialkylaminomethyl)arylboronate system.
AB  - o-(Pyrrolidinylmethyl)phenylboronic acid (4) and its complexes with bifunctional
      substrates such as catechol, alpha-hydroxyisobutyric acid, and hydrobenzoin have
      been studied in detail by X-ray crystallography, (11)B NMR, and computational
      analysis. The N-B interactions in analogous boronic acids and esters have been
      extensively cited in molecular recognition and chemosensing literature. The focal
      point of this study was to determine the factors that are pertinent to the
      formation of an intramolecular N-B dative bond. Our structural study predicts
      that the formation of an N-B dative bond, and/or solvent insertion to afford a
      tetrahedral boronate anion, depends on the solvent and the complexing substrate
      present. Specifically, from (11)B NMR studies, complexation of 4 with electron
      withdrawing and/or vicinally bifunctionalized substrates promotes both the
      formation of N-B dative bonds and the solvation of sp(2) boron to a tetrahedral
      sp(3) boronate. In the solid state, the presence of an N-B dative bond in the
      complex of 4 and catechol (7) depends on the solvent from which it crystallizes.
      From chloroform, an N-B bond was observed, whereas from methanol, a methoxylated
      boronate was formed, where the methoxy group is hydrogen-bonded with the
      neighboring tertiary ammonium ion. The structural optimization of compounds 4 and
      7 using density functional theory in a simulated water continuum also predicts
      that complexation of 4 and catechol promotes either the formation of an N-B bond
      or solvolysis if 1 equiv of water is present. The conclusion from this study will
      help in the design of future chemosensing technologies based on o-(N,N
      dialkylaminomethyl)arylboronate scaffolds that are targeting physiologically
      important substances such as saccharides, alpha-hydroxycarboxylates, and
      catecholamines.

PMID- 16433540
TI  - Combination of a modified scoring function with two-dimensional descriptors for
      calculation of binding affinities of bulky, flexible ligands to proteins.
AB  - Bulky, flexible molecules such as peptides and peptidomimetics are often used as
      lead compounds during the drug discovery process. Pathophysiological events,
      e.g., the formation of amyloid fibrils in Alzheimer's disease, the conformational
      changes of prion proteins, or beta-secretase activity, may be successfully
      hindered by the use of rationally designed peptide sequences. A key step in the
      molecular engineering of such potent lead compounds is the prediction of the
      energetics of their binding to the macromolecular targets. Although sophisticated
      experimental and in silico methods are available to help this issue, the
      structure-based calculation of the binding free energies of large, flexible
      ligands to proteins is problematic. In this study, a fast and accurate
      calculation strategy is presented, following modification of the scoring function
      of the popular docking program package AutoDock and the involvement of ligand
      based two-dimensional descriptors. Quantitative structure-activity relationships
      with good predictive power were developed. Thorough cross-validation tests and
      verifications were performed on the basis of experimental binding data of
      biologically important systems. The capabilities and limitations of the ligand
      based descriptors were analyzed. Application of these results in the early phase
      of lead design will contribute to precise predictions, correct selections, and
      consequently a higher success rate of rational drug discovery.

PMID- 16433541
TI  - A three-state mechanism for DNA hairpin folding characterized by multiparameter
      fluorescence fluctuation spectroscopy.
AB  - The folding of a dye-quencher labeled DNA hairpin molecule was investigated using
      fluorescence autocorrelation and cross-correlation spectroscopy (FCS) and photon
      counting histogram analysis (PCH). The autocorrelation and cross-correlation
      measurements revealed the flow and diffusion times of the DNA molecules through
      two spatially offset detection volumes, the relaxation time of the folding
      reaction, and the total concentration of DNA molecules participating in the
      reaction. The PCH measurements revealed the equilibrium distribution of DNA
      molecules in folded and unfolded conformations and the specific brightnesses of
      the fluorophore in each conformational state. These measurements were carried out
      over a range of NaCl concentrations, from those that favored the open form of the
      DNA hairpin to those that favored the closed form. DNA melting curves obtained
      from each sample were also analyzed for comparison. It was found that the
      reactant concentrations were depleted as the reaction progressed and that the
      equilibrium distributions measured by FCS and PCH deviated from those obtained
      from the melting curve analyses. These observations suggest a three-state
      mechanism for the DNA hairpin folding reaction that involves a stable
      intermediate form of the DNA hairpin. The reaction being probed by FCS and PCH is
      suggested to be a rapid equilibrium between open and intermediate conformations.
      Formation of the fully closed DNA hairpin is suggested to occur on a much longer
      time scale than the FCS and PCH measurement time. The closed form of the hairpin
      thus serves as a sink into which the reactants are depleted as the reaction
      progresses.

PMID- 16433542
TI  - Near 0 eV electrons attach to nucleotides.
AB  - To elucidate the mechanism of the nascent stage of DNA strand breakage by low
      energy electrons, theoretical investigations of electron attachment to
      nucleotides have been performed by the reliably calibrated B3LYP/DZP++ approach
      (Chem. Rev. 2002, 102, 231). The 2'-deoxycytidine-3'-monophosphate (3'-dCMPH) and
      its phosphate-deprotonated anion (3'-dCMP(-)) have been selected herein as
      models. This investigation reveals that 3'-dCMPH is able to capture near 0 eV
      electrons to form a radical anion which has a lower energy than the corresponding
      neutral species in both the gas phase and aqueous solution. The excess electron
      density is primarily located on the base of the nucleotide radical anion. The
      electron detachment energy of this pyrimidine-based radical anion is high enough
      that subsequent phosphate-sugar C-O sigma bond breaking or glycosidic bond
      cleavage is feasible. Although the phosphate-centered radical anion of 3'-dCMPH
      is not stable in the gas phase, it may be stable in aqueous solution. However, an
      incident electron with kinetic energy less than 4 eV might not be able to
      effectively produce the phosphate-centered radical anion either in solution or in
      the gas phase. This research also suggests that the electron affinity of the
      nucleotides is independent of the counterion in aqueous solution.

PMID- 16433543
TI  - Switchable surface properties through the electrochemical or biocatalytic
      generation of Ag0 nanoclusters on monolayer-functionalized electrodes.
AB  - The electroswitchable and the biocatalytic/electrochemical switchable interfacial
      properties of a Ag(+)-biphenyldithiol (BPDT) monolayer associated with a Au
      surface are described. Upon the application of a potential corresponding to -0.2
      V the Ag(+)-BPDT is reduced to the Ag(0)-BPDT interface, and silver nanoclusters
      are generated on the interface. The application of a potential that corresponds
      to 0.2 V reoxidizes the monolayer to the Ag(+)-BPDT monolayer. The reversible
      electrochemical transformation of the Ag(+)-BPDT monolayer and of the Ag(0)-BPDT
      surface was followed by electrochemical means and surface plasmon resonance
      spectroscopy (SPR). The SPR experiments enabled us to follow the kinetics of
      nanoclustering of Ag(0) on the surface. The hydrophobic/hydrophilic properties of
      the surface are controlled by the electrochemically induced transformation of the
      interface between the Ag(+)-BPDT and Ag(0)-BPDT states. The Ag(0)-BPDT monolayer
      reveals enhanced hydrophilicity. The hydrophobic/hydrophilic properties of the
      interface were probed by contact angle measurements and force interactions with a
      hydrophobically-functionalized AFM tip. The Ag(0)-BPDT interface was also
      biocatalytically generated using alkaline phosphatase, AlkPh, and p-aminophenyl
      phosphate as substrate. The biocatalytically generated p-aminophenol reduces
      Ag(+) ions associated with the surface to Ag(0) nanoclusters. This enables the
      cyclic biocatalytic/electrochemical control of the surface properties of the
      modified electrode.

PMID- 16433544
TI  - Aminoglycoside-induced reduction in nucleotide mobility at the ribosomal RNA A
      site as a potentially key determinant of antibacterial activity.
AB  - Steady-state and time-resolved fluorescence techniques have been used to
      characterize the energetics and dynamics associated with the interaction of an E.
      coli 16 S rRNA A-site model oligonucleotide and four aminoglycoside antibiotics
      that exhibit a broad range of antibacterial activity. The results of these
      characterizations suggest that aminoglycoside-induced reduction in the mobility
      of an adenine residue at position 1492 of the rRNA A-site is a more important
      determinant of antibacterial activity than drug affinity for the A-site. This
      observation is consistent with a recently proposed model for the mechanism of
      protein synthesis inhibition by aminoglycosides that invokes a drug-induced
      alteration in the conformational equilibrium of the rRNA A-site (centered around
      the conserved adenine residues at positions 1492 and 1493), which, in turn,
      promotes an enhanced interaction between the rRNA and the minihelix formed by the
      tRNA anticodon and the mRNA codon, even when the anticodon is noncognate.
      Regarded as a whole, the results reported here indicate that the rational design
      of antibiotics that target the 16 S rRNA A-site requires consideration of not
      only the structure and energetics of the drug-RNA complex but also the dynamics
      associated with that complex.

PMID- 16433545
TI  - Catalytic mechanism and product specificity of the histone lysine
      methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple initial
      structures.
AB  - Histone lysine methylation is emerging as an important mechanism to regulate
      chromatin structure and gene activity. To provide theoretical understanding of
      its reaction mechanism and product specificity, ab initio quantum
      mechanical/molecular mechanical free energy (QM/MM-FE) calculations and molecular
      dynamics simulations have been carried out to investigate the histone lysine
      methyltransferase SET7/9. It is found that the methyl-transfer reaction catalyzed
      by SET7/9 is a typical in-line S(N)2 nucleophilic substitution reaction with a
      transition state of 70% dissociative character. The calculated average free
      energy barrier at the MP2(6-31+G) QM/MM level is 20.4 +/- 1.1 kcal/mol,
      consistent with the activation barrier of 20.9 kcal/mol estimated from the
      experimental reaction rate. The barrier fluctuation has a strong correlation with
      the nucleophilic attack distance and angle in the reactant complex. The
      calculation results show that the product specificity of SET7/9 as a
      monomethyltransferase is achieved by disrupting the formation of near-attack
      conformations for the dimethylation reaction.

PMID- 16433546
TI  - Monitoring lipid membrane translocation of sodium dodecyl sulfate by isothermal
      titration calorimetry.
AB  - We establish high-sensitivity isothermal titration calorimetry (ITC) as a fast,
      reliable, and versatile tool for assessing membrane translocation of charged
      compounds. A combination of ITC uptake and release titrations can discriminate
      between the two extreme cases of half-sided binding and complete transbilayer
      equilibration on the experimental time scale. To this end, we derive a general
      fit function for both assays that allows for incorporation of different membrane
      partitioning models. Electrostatic effects are taken into account with the aid of
      Gouy-Chapman theory, thus rendering uptake and release experiments amenable to
      the investigation of charged solutes. This is exemplified for the flip-flop of
      the anionic detergent sodium dodecyl sulfate (SDS) across the membranes of 100-nm
      diameter unilamellar vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) in aqueous solution (10 mM phosphate buffer, 154 mM NaCl,
      pH 7.4). If repulsive electrostatic forces are accounted for adequately, SDS
      binding to POPC membranes can be evaluated on the basis of ideal mixing in all
      phases. At 25 degrees C, the intrinsic partition coefficient between the
      interfacial aqueous phase and the membrane amounts to 3.5 x 10(6); however,
      detergent flip-flop is negligibly slow under these conditions. Raising the
      temperature to 65 degrees C lowers the intrinsic partition coefficient to 1.4 x
      10(6) but enables rapid transbilayer distribution of the detergent and,
      therefore, binding to or desorption from both membrane leaflets. Thus, combining
      a surface partition equilibrium with simple electrostatic theory appears highly
      useful in monitoring transmembrane movement of ionic compounds by ITC, thereby
      eliminating the need for specific reporter groups.

PMID- 16433547
TI  - Computational insights into the mechanism of radical generation in B12-dependent
      methylmalonyl-CoA mutase.
AB  - ONIOM calculations have provided novel insights into the mechanism of homolytic
      Co-C5' bond cleavage in the 5'-deoxyadenosylcobalamin cofactor catalyzed by
      methylmalonyl-CoA mutase. We have shown that it is a stepwise process in which
      conformational changes in the 5'-deoxyadenosine moiety precede the actual
      homolysis step. In the transition state structure for homolysis, the Co-C5' bond
      elongates by approximately 0.5 Angstroms from the value found in the substrate
      bound reactant complex. The overall barrier to homolysis is approximately 10
      kcal/mol, and the radical products are approximately 2.5 kcal/mol less stable
      than the initial ternary complex of enzyme, substrate, and cofactor. The movement
      of the deoxyadenosine moiety during the homolysis step positions the resulting 5'
      deoxyadenosyl radical for the subsequent hydrogen atom transfer from the
      substrate, methylmalonyl-CoA.

PMID- 16433549
TI  - Effects of functionalization, catenation, and variation of the metal oxide and
      organic linking units on the low-pressure hydrogen adsorption properties of metal
      organic frameworks.
AB  - The dihydrogen adsorption isotherms of eight metal-organic frameworks (MOFs),
      measured at 77 K up to a pressure of 1 atm, have been examined for correlations
      with their structural features. All materials display approximately Type I
      isotherms with no hysteresis, and saturation was not reached for any of the
      materials under these conditions. Among the six isoreticular MOFs (IRMOFs)
      studied, the catenated materials exhibit the largest capacities on a molar basis,
      up to 9.8 H(2) per formula unit. The addition of functional groups (-Br, -NH(2), 
      C(2)H(4)-) to the phenylene links of IRMOF-1 (MOF-5), or their replacement with
      thieno[3,2-b]thiophene moieties in IRMOF-20, altered the adsorption behavior by a
      minor amount despite large variations in the pore volumes of the resulting
      materials. In contrast, replacement of the metal oxide units with those
      containing coordinatively unsaturated metal sites resulted in greater H(2)
      uptake. The enhanced affinities of these materials, MOF-74 and HKUST-1, were
      further demonstrated by calculation of the isosteric heats of adsorption, which
      were larger across much of the range of coverage examined, compared to those of
      representative IRMOFs. The results suggest that under low-loading conditions, the
      H(2) adsorption behavior of MOFs can be improved by imparting larger charge
      gradients on the metal oxide units and adjusting the link metrics to constrict
      the pore dimensions; however, a large pore volume is still a prerequisite
      feature.

PMID- 16433550
TI  - Chemo-regioselectivity in heterogeneous catalysis: competitive routes for C = O
      and C = C hydrogenations from a theoretical approach.
AB  - The usual empirical rule stating that the C=C bond is more reactive than the C=O
      group for catalytic hydrogenations of unsaturated aldehydes is invalidated from
      the present study. Density functional theory calculations of all the competitive
      hydrogenation routes of acrolein on Pt(111) reveals conversely that the attack at
      the C=O bond is systematically favored. The explanation of such catalytic
      behavior is the existence of metastable precursor states for the O-H bond
      formation showing that the attack at the oxygen atom follows a new preferential
      mechanism where the C=O moiety is not directly bonded with the Pt surface atoms,
      hence yielding an intermediate pathway between Langmuir-Hinshelwood and Rideal
      Eley general types of mechanisms. When the whole catalytic cycle is considered,
      our results reconcile with experimental studies devoted to hydrogenation of
      acrolein on Pt, since the desorption step of the partially hydrogenated product
      (unsaturated alcohol versus saturated aldehyde) plays a key role for the
      selectivity.

PMID- 16433548
TI  - Alkaline phosphatase mono- and diesterase reactions: comparative transition state
      analysis.
AB  - Enzyme-catalyzed phosphoryl transfer reactions have frequently been suggested to
      proceed through transition states that are altered from their solution
      counterparts. Previous work with Escherichia coli alkaline phosphatase (AP),
      however, suggests that this enzyme catalyzes the hydrolysis of phosphate
      monoesters through a loose, dissociative transition state, similar to that in
      solution. AP also exhibits catalytic promiscuity, with a low level of
      phosphodiesterase activity, despite the tighter, more associative transition
      state for phosphate diester hydrolysis in solution. Because AP is evolutionarily
      optimized for phosphate monoester hydrolysis, it is possible that the active site
      environment alters the transition state for diester hydrolysis to be looser in
      its bonding to the incoming and outgoing groups. To test this possibility, we
      have measured the nonenzymatic and AP-catalyzed rate of reaction for a series of
      substituted methyl phenyl phosphate diesters. The values of beta(lg) and
      additional data suggest that the transition state for AP-catalyzed phosphate
      diester hydrolysis is indistinguishable from that in solution. Instead of
      altering transition state structure, AP catalyzes phosphoryl transfer reactions
      by recognizing and stabilizing transition states similar to those in aqueous
      solution. The AP active site therefore has the ability to recognize different
      transition states, a property that could assist in the evolutionary optimization
      of promiscuous activities.

PMID- 16433552
TI  - Suppressing aggregation in a large polycyclic aromatic hydrocarbon.
AB  - With the approach presented herein, a large aromatic pi-system is synthesized,
      which shows extraordinarily high solubility and an effective suppression of
      aggregation. This was due to a distortion of the aromatic core by bulky tert
      butyl groups and the solubilizing effects of alkyl chains in the corona of the
      aromatic core. Therefore not only the processing and cleaning of the materials
      with standard laboratory techniques became possible, but moreover the first
      structure-rich UV/vis and a resolved (1)H NMR spectra for an aromatic system two
      times larger than hexa-peri-hexabenzocoronene were recorded. The bulk properties
      in an extruded fiber as well as on the surface showed a columnar self-assembly
      including a phase in which a homeotropic alignment on a substrate was observed,
      which turns the material into an interesting candidate for future applications in
      electronic devices.

PMID- 16433551
TI  - Guest exchange dynamics in an M4L6 tetrahedral host.
AB  - Guest exchange in an M(4)L(6) supramolecular assembly was previously demonstrated
      to proceed through a nonrupture mechanism in which guests squeeze through
      apertures in the host structure and not through larger portals created by partial
      assembly dissociation. Focusing on the [Ga(4)L(6)](12-) assembly [L = 1,5
      bis(2',3'-dihydroxybenzamido)naphthalene], the host-guest kinetic behavior of
      this supramolecular capsule is defined. Guest self-exchange rates at varied
      temperatures and pressures were measured to determine activation parameters,
      revealing negative DeltaS and positive DeltaV values [PEt(4)(+): DeltaH = 74(3)
      kJ mol(-1), DeltaS = -46(6) J mol(-1) K(-1), k(298) = 0.003 s(-)); NEt(4)(+):
      DeltaH = 69(2) kJ mol(-1), DeltaS = -52(5) J mol(-1) K(-1), k(298) = 0.009 s(-1);
      NMe(2)Pr(2)(+): DeltaH = 52(2) kJ mol(-1), DeltaS = -56(7) J mol(-1) K(-1),
      DeltaV = +13(1) cm(3) mol(-1), k(298) = 4.4 s(-1); NPr(4)(+): DeltaH = 42(1) kJ
      mol(-1), DeltaS = -102(4) J mol(-1) K(-1), DeltaV = +31(2) cm(3) mol(-1), k(298)
      = 1.4 s(-1)]. In PEt(4)(+) for NEt(4)(+) exchange reactions, egress of the
      initial guest (G1) is found to be rate determining, with increasing G1 and G2
      (the displacing guest) concentrations inhibiting guest exchange. This inhibition
      is explained by the decreased flexibility of the host imparted by exterior, or
      exohedral, guest interactions by both the G1 and G2 guests. Blocking the
      exohedral host sites with high concentrations of the smaller NMe(4)(+) cation (a
      weak endohedral guest) enhances PEt(4)(+) for NEt(4)(+) guest exchange rates.
      Finally, guest displacement reactions also demonstrate the sensitivity of guest
      exchange to thermodynamic endohedral guest binding affinities. When the initial
      guest (G1) has a weaker affinity for the host, G2 concentration dependence is
      observed in addition to dependence on the G2 binding strength.

PMID- 16433553
TI  - Organization of acenes with a cruciform assembly motif.
AB  - This study explores the assembly in the crystalline state of a class of
      pentacenes that are substituted along their long edges with aromatic rings
      forming rigid, cruciform molecules. The crystals were grown from the gas phase,
      and their structures were compared with DFT-optimized geometries. Both
      crystallographic and computed structures show that a planar acene core is the
      exception rather than the rule. In the assembly of these molecules, the phenyl
      groups block the herringbone motif and further guide the arrangement of the acene
      core into higher order structures. The packing for the phenyl-substituted
      derivatives is dictated by close contacts between the C-H's of the pendant
      aromatic rings and the carbons at the fusions in the acene backbone. Using
      thiophene substituents instead of phenyls creates cofacially stacked acenes. In
      thin films, the thiophene-substituted derivative forms devices with good
      electrical properties: relatively high mobility, high ON/OFF ratios, and low
      threshold voltage for device activation. An unusual result is obtained for the
      decaphenyl pentacene when devices are fabricated on its crystalline surface.
      Although its acene cores are well isolated from each other, this material still
      exhibits good electrical properties.

PMID- 16433554
TI  - Enantioselective syntheses of georgyone, arborone, and structural relatives.
      Relevance to the molecular-level understanding of olfaction.
AB  - Georgyone (1) and arborone (2), powerful woody odorants, have been synthesized
      enantioselectively along with their enantiomers. Several structural relatives of
      1 and 2 have also been made enantioselectivity in order to probe the molecular
      details of the binding of 1 and 2 to the olfactory G-protein-coupled receptors
      which they activate. These studies have led to a number of conclusions regarding
      the structural requirements for woody odor, including absolute configuration,
      critical methyl substitution, and the spatial orientation of the key methyl
      groups. Odorants 1 and 2 bind to at least 10 mouse olfactory receptors, lending
      support to the combinatorial model for odor perception/differentiation. The
      implications of this work with regard to possible receptor binding modes are
      discussed.

PMID- 16433555
TI  - Growth kinetics of heterostructured GaP-GaAs nanowires.
AB  - We have studied the vapor-liquid-solid (VLS) growth dynamics of GaP and GaAs in
      heterostructured GaP-GaAs nanowires. The wires containing multiple GaP-GaAs
      junctions were grown by the use of metal-organic vapor phase-epitaxy (MOVPE) on
      SiO(2), and the lengths of the individual sections were obtained from
      transmission electron microscopy. The growth kinetics has been studied as a
      function of temperature and the partial pressures of the precursors. We found
      that the growth of the GaAs sections is limited by the arsine (AsH(3)) as well as
      the trimethylgallium (Ga(CH(3))(3)) partial pressures, whereas the growth of GaP
      is a temperature-activated, phosphine(PH(3))-limited process with an activation
      energy of 115 +/- 6 kJ/mol. The PH(3) kinetics obeys the Hinshelwood-Langmuir
      mechanism, indicating that the dissociation reaction of adsorbed PH(3) into PH(2)
      and H on the catalytic gold surface is the rate-limiting step for the growth of
      GaP. In addition, we have studied the competitive thin layer growth on the
      sidewalls of the nanowires. Although the rate of this process is 2 orders of
      magnitude lower than the growth rate of the VLS mechanism, it competes with VLS
      growth and results in tapered nanowires at elevated temperatures.

PMID- 16433556
TI  - Bis(allyl)-ruthenium(IV) complexes as highly efficient catalysts for the redox
      isomerization of allylic alcohols into carbonyl compounds in organic and aqueous
      media: scope, limitations, and theoretical analysis of the mechanism.
AB  - The catalytic activity of the bis(allyl)-ruthenium(IV) dimer [[Ru(eta(3):eta(3)
      C(10)H(16))(mu-Cl)Cl](2)] (C(10)H(16) = 2,7-dimethylocta-2,6-diene-1,8-diyl) (1),
      and that of its mononuclear derivatives [Ru(eta(3):eta(3)-C(10)H(16))Cl(2)(L)] (L
      = CO, PR(3), CNR, NCR) (2) and [Ru(eta(3):eta(3)-C(10)H(16))Cl(NCMe)(2)][SbF(6)]
      (3), in the redox isomerization of allylic alcohols into carbonyl compounds, both
      in tetrahydrofuran and in water, is reported. In particular, a variety of allylic
      alcohols have been quantitatively isomerized using [[Ru(eta(3):eta(3)
      C(10)H(16))(mu-Cl)Cl](2)] (1) as catalyst, the reactions proceeding in all cases
      faster in water. Remarkably, complex 1 has been found to be the most efficient
      catalyst reported to date for this particular transformation, leading to TOF and
      TON values up to 62,500 h(-1) and 1 500,000, respectively. Moreover, catalyst 1
      can be recycled and is capable of performing allylic alcohol isomerizations even
      in the presence of conjugated dienes, which are known to be strong poisons in
      isomerization catalysis. On the basis of both experimental data and theoretical
      calculations (DFT), a complete catalytic cycle for the isomerization of 2-propen
      1-ol into propenal is described. The potential energy surfaces of the cycle have
      been explored at the B3LYP/6-311 + G(d,p)//B3LYP/6-31G(d,p) + LAN2DZ level. The
      proposed mechanism involves the coordination of the oxygen atom of the allylic
      alcohol to the metal. The DFT energy profile is consistent with the experimental
      observation that the reaction only proceeds under heating. Calculations predict
      the catalytic cycle to be strongly exergonic, in full agreement with the high
      yields experimentally observed.

PMID- 16433557
TI  - An intramolecular Diels-Alder approach to the eunicellins: enantioselective total
      syntheses of ophirin B and astrogorgin.
AB  - The enantioselective syntheses of the eunicellins ophirin B and astrogorgin have
      been completed. Ring-closing metatheses provide efficient access to the oxonene
      rings, and highly diastereoselective intramolecular Diels-Alder reactions
      resulted in the formation of the hydrobenzofuran portion of the molecules.

PMID- 16433559
TI  - Rechargeable LI2O2 electrode for lithium batteries.
AB  - Rechargeable lithium batteries represent one of the most important developments
      in energy storage for 100 years, with the potential to address the key problem of
      global warming. However, their ability to store energy is limited by the quantity
      of lithium that may be removed from and reinserted into the positive
      intercalation electrode, Li(x)CoO(2), 0.5 < x < 1 (corresponding to 140 mA.h g(
      1) of charge storage). Abandoning the intercalation electrode and allowing Li to
      react directly with O(2) from the air at a porous electrode increases the
      theoretical charge storage by a remarkable 5-10 times! Here we demonstrate two
      essential prerequisites for the successful operation of a rechargeable Li/O(2)
      battery; that the Li(2)O(2) formed on discharging such an O(2) electrode is
      decomposed to Li and O(2) on charging (shown here by in situ mass spectrometry),
      with or without a catalyst, and that charge/discharge cycling is sustainable for
      many cycles.

PMID- 16433564
TI  - ASHP s 2015 initiative: a collective effort to improve pharmacy practice in
      hospitals and health-systems in the United States.

PMID- 16433565
TI  - [Monitoring of vancomycin plasma levels in patients undergoing hemodialysis].
AB  - OBJECTIVE: The aim of this study was to confirm whether patients undergoing
      dialysis and treated with vancomycin 1 g/week or 500 mg/48 hours reach optimum
      plasma levels (10-25 mcg/ml). METHOD: Thirty two patients were included with a
      total number of 34 infectious events. The most commonly used dose was 1 g/week
      (67.6% of infectious events), versus 500 mg/48 hours (32.4%). Low ultrafiltration
      membranes were used more frequently (64.7%) than high ultrafiltration membranes
      (35.3%).Vancomycin was infused over an one-hour period during the last hour of
      the hemodialysis session and plasma samples were drawn prior to the beginning of
      the session. Samples were analyzed using fluorescent polarization immunoassays.
      RESULTS: Mean concentration results for the total population did not reach
      optimum values (10-25 mg/ml). In the group receiving 500 mg/48 hours, optimum
      mean values were not reached in any of the determinations, whereas in the group
      receiving 1 g/week, optimum values were reached in the fourth determination. Mean
      plasma levels of the antibiotic were below optimum values, regardless the type of
      membrane used, either low or high ultrafiltration. CONCLUSIONS: Based on the
      above results, we recommend titration of the vancomycin dose in this group of
      patients and the administration of a loading dose of 20 mg/kg during the last
      hour of the hemodialysis session, followed by a maintenance dose of 7 mg/kg after
      each session, as well as the monitoring of the drug levels in this group of
      patients.

PMID- 16433558
TI  - Models of the membrane-bound cytochromes: mossbauer spectra of crystalline low
      spin ferriheme complexes having axial ligand plane dihedral angles ranging from 0
      degree to 90 degrees.
AB  - Crystalline samples of four low-spin Fe(III) octaalkyltetraphenylporphyrinate and
      two low-spin Fe(III) tetramesitylporphyrinate complexes, all of which are models
      of the bis-histidine-coordinated cytochromes of mitochondrial complexes II, III,
      and IV and chloroplast complex b(6)f, and whose molecular structures and EPR
      spectra have been reported previously, have been investigated in detail by
      Mossbauer spectroscopy. The six complexes and the dihedral angles between axial
      ligand planes of each are [(TMP)Fe(1-MeIm)(2)]ClO(4) (0 degree), paral
      [(OMTPP)Fe(1-MeIm)(2)]Cl (19.5 degrees), paral-[(TMP)Fe(5-MeHIm)(2)]ClO(4) (26
      degrees, 30 degrees for two molecules in the unit cell whose EPR spectra
      overlap), [(OETPP)Fe(4-Me(2)NPy)(2)]Cl (70 degrees), perp-[(OETPP)Fe(1
      MeIm)(2)]Cl (73 degrees), and perp-[(OMTPP)Fe(1-MeIm)(2)]Cl (90 degrees). Of
      these, the first three have been shown to exhibit normal rhombic EPR spectra,
      each with three clearly resolved g-values, while the last three have been shown
      to exhibit "large g(max)" EPR spectra at 4.2 K. It is found that the hyperfine
      coupling constants of the complexes are consistent with those reported previously
      for low-spin ferriheme systems, with the largest-magnitude hyperfine coupling
      constant, A(zz), being considerably smaller for the "parallel" complexes (400-540
      kG) than for the strictly perpendicular complex (902 kG), A(xx) being negative
      for all six complexes, and A(zz) and A(xx) being of similar magnitude for the
      "parallel" complexes (for example, for [(TMP)Fe(1-MeIm)(2)]Cl, A(zz) = 400 kG,
      A(xx) = -400 kG). In all cases, A(yy) is small but difficult to estimate with
      accuracy. With results for six structurally characterized model systems, we find
      for the first time qualitative correlations of g(zz), A(zz), and DeltaE(Q) with
      axial ligand plane dihedral angle Deltavarphi.

PMID- 16433566
TI  - [Treatment of infections by wide spectrum betalactamase-producing microorganisms:
      a new therapeutic challenge].

PMID- 16433568
TI  - [Follow-up of the use of metformin among the high risk population].
AB  - OBJECTIVE: To perform a follow-up of the use of metformin in order to ensure the
      appropriate prescription of the drug among the population with the highest risk
      of adverse reactions. METHOD: A prospective follow-up was conducted of the use of
      metformin during a four-month period. In the patients recruited for the study,
      the following data were recorded: age, sex, weight and height, cause of
      hospitalization, pharmacotherapeutic profile, origin of the prescription (prior
      to hospitalization or during the hospital stay), glycemia, renal function, side
      effects and cause of the discontinuation of the treatment, if appropriate.
      RESULTS: The mean number of patients hospitalized each day during the study
      period was 352 (standard deviation +/- 36,8), the mean age was 73 years (33-102)
      and the total number of patients studied was 135, with 46% of males.Since
      prescription of metformin is contraindicated in patients with creatinine values >
      0.132 mMol/L, renal function was monitored. Based on the data of 20 patients, six
      pharmaceutical interventions were performed in order to recommend the
      discontinuation of the treatment, which was accepted in 83% of the cases. Side
      effects and glycemia were also recorded. CONCLUSIONS: During the follow-up
      period, we did not observe any severe side effects such as associated lactic
      acidosis, although in some cases metformin was prescribed to patients in which it
      was not recommended. However, the follow-up of patients is important, since we
      have observed side effects (diarrhea) that require reduction of the dose of
      metformin.

PMID- 16433567
TI  - [Quality improvement of the filling medication trolleys process, for an unit-dose
      drug distribution system].
AB  - OBJECTIVE: To assess the quality of filling medication trolleys process for an
      unit-dose drug distribution system, after the implantation of a protocol. METHOD:
      Five criteria were defined: four were related to the medication given to the
      patient, and one criterion was related to the patient's identification. At the
      same time, it was designed a standardized protocol of filling medication trolleys
      process and it was evaluated the degree of compliance with the criteria on all
      the hospitalized patients medication drawers in two clinical units. The
      fulfilment of the criteria was measured both before and after the implantation of
      the protocol, for fourteen and seven days respectively. RESULTS: In the first
      evaluation the number of errors was 0.84/medication drawer. After the
      implantation of the protocol, the total number of errors after correction for
      sample size decreased at 0.22/medication drawer. The degree of compliance
      improved for all the criteria, and differences were statistically significant for
      the criteria with most errors. CONCLUSIONS: The implantation of a protocol
      significantly improved two of the five quality criteria studied in the filling
      medication trolleys process. The patient's identification has been revealed as a
      fundamental aspect of intervention in the dispensation quality.

PMID- 16433569
TI  - [Pharmaceutical care program for pediatric patients receiving antiretroviral
      therapy].
AB  - OBJECTIVE: To present a pharmaceutical care program for pediatric patients
      receiving antiretroviral therapy. METHOD: In order to establish the
      pharmaceutical care procedure, papers published up to 2004 on the pharmaceutical
      care provided to patients receiving antiretroviral therapy were reviewed through
      a search in Medline and the journal Farmacia Hospitalaria. In addition,
      bibliographic references that can be systematically used to analyze the
      pharmacotherapy of each patient have been selected. RESULTS: The pharmaceutical
      care procedure is divided in three stages (data collection, analysis of the
      pharmacotherapeutic profile and resolution of the drug-related problems
      identified) that take place through a semi-structured type of interview. In order
      to systematize the role of the pharmacist, a table with information on
      antiretroviral drugs used in Pediatrics was created, as well as an information
      three-page leaflet and a data collection form. CONCLUSIONS: The program includes
      the goals of the pharmaceutical care process as defined in the recommendations of
      GESIDA-SEFH-National AIDS Plan 2004 and systematizes the proposed intervention
      strategies, in an attempt to provide the patient and the caregiver with the
      information required for an optimum management, in the most comprehensive way and
      tailored to their individual characteristics.

PMID- 16433570
TI  - [Enfuvirtide: first drug of a new family of antiretroviral agents].
AB  - Enfuvirtide or T-20 is the first drug approved by the FDA and the EMEA within the
      group of fusion inhibitors. Its mechanism of action is based on the blockade of
      the entry of the HIV to the body cells. Enfuvirtide is recommended in combination
      with other antiretroviral drugs for the treatment of patients infected by HIV
      that have developed resistance or intolerance to other prior antiretroviral
      therapies. Clinical trials have shown the effectiveness and safety of the
      treatment with this drug. Side effects most commonly reported are local reactions
      in the injection site. Enfuvirtide contributes to increase the therapeutic
      arsenal available for the management of the HIV infection, providing rescue
      therapy for patients in which prior treatments have failed.

PMID- 16433571
TI  - [Improved safety of the drug prescription system: role of the specialist in
      hospital pharmacy].

PMID- 16433572
TI  - [Common law study of the legal responsibility of health care staff related to
      drug reformulation].
AB  - OBJECTIVE: To analyze the responsibility of health care staff in drug
      reformulation (change of dose, pharmaceutical form or route of administration of
      medicinal products) based on the common law of the High Court and the National
      Court. METHOD: Search and analysis of common law and legal studies included in
      databases "El Derecho", "Difusion Juridica" and "Indret". RESULTS: Health care
      staff has means--not outcomes--obligations according to the care standards
      included in the "Lex Artis" that can go beyond the mere legal standards. Failure
      to apply these care standards, denial of assistance or disrespect to the autonomy
      of the patient can be negligent behavior. We found 4 cases in common law. In the
      two cases in which care standards were complied with, including reformulation,
      health care professionals were acquitted, whereas in the other two cases in which
      reformulations were not used even though the "Lex Artis" required them, the
      professionals were condemned. CONCLUSIONS: Reformulation of medicinal products,
      as set forth in the Lex Artis, is a practice accepted by the High Court and the
      National Court and failure to use it when the scientific knowledge advises so is
      a cause for conviction.

PMID- 16433573
TI  - [Association between immunosuppression and no melanoma skin cancer in patients
      with kidney transplantation].

PMID- 16433574
TI  - [Comments about the automated-procedure].

PMID- 16433578
TI  - Pharmacogenetics for off-patent antipsychotics: reframing the risk for tardive
      dyskinesia and access to essential medicines.
AB  - First-generation antipsychotics (FGAs) induce tardive dyskinesia, a debilitating
      involuntary hyperkinetic movement disorder, in 20-50% of individuals with a
      psychotic illness during chronic treatment. There is presently no curative
      treatment or definitive predictive test for tardive dyskinesia. The authors note
      that the three antipsychotic drugs enlisted in the most recent (14th) World
      Health Organization Model List of Essential Medicines--chlorpromazine,
      fluphenazine and haloperidol--belong to the FGA therapeutic class. In this
      regard, the need to choose between the competing objectives of ensuring global
      access to affordable and efficacious medicines, such as FGAs, and the formidable
      long-term risk for tardive dyskinesia, may create an ethical conundrum.
      Pharmacogenetics has thus far been conceptually framed as a tool to individualize
      therapy with new drugs under patent protection. However, the authors suggest that
      pharmacogenetics may also improve access to pharmacotherapy through the
      reintroduction of affordable second-line generic drugs or FGAs with suboptimal
      safety, as first-line therapy, in targeted subpopulations in whom they present a
      lower risk for tardive dyskinesia. To impact positively on global public health
      and distributive justice, a directory complementary to the essential medicines
      library--one that enlists the 'essential biomarkers' required for optimal
      pharmacotherapy--may benefit patients who do not have adequate access to new
      antipsychotic medications. This review discusses pharmacogenetic associations of
      tardive dyskinesia that are in part supported by meta-analyses and the oxidative
      stress-neuronal degeneration hypothesis.

PMID- 16433579
TI  - Economic implications of nonadherence to highly active antiretroviral treatment
      in HIV patients.
AB  - Until now, the economic implications of nonadherence to drug therapies have been
      mostly assessed in a cost perspective and understood as the impact of
      nonadherence behaviours on the cost-effectiveness ratios of particular therapies.
      In HIV disease, some modelling approaches have suggested that high adherence
      levels might improve the cost-effectiveness of highly active antiretroviral
      treatment regimens. However, there is an urgent need for research directly
      observing and measuring the costs of nonadherence behaviours. In addition to this
      cost perspective, the authors argue that the economic impact of nonadherence
      should also be studied in a microeconomic--patient-oriented--perspective. Major
      implications of this microeconomic perspective are drawn. First, the
      microeconomic approach highlights that nonadherence may often be a rational
      choice of the patient, thus suggesting new ways for improving adherence. Second,
      it implies that the adherence behaviour can be interpreted as an indicator of
      patients' subjective valuation of highly active antiretroviral treatment
      therapies; in particular, higher levels of adherence are associated with higher
      patient well-being. Third, it shows that the adherence behaviour cannot be
      regarded as an exogenous variable when the impact of adherence on health outcome
      or on cost-effectiveness ratios is studied, thus requiring the use of specific
      statistical or econometric methods.

PMID- 16433580
TI  - Cost-effectiveness of pharmacotherapy for autoimmune hepatitis.
AB  - In > 80% of patients with autoimmune hepatitis, steroid therapy alone or in
      combination with azathioprine results in disease remission. Treatment response
      results in reversal of fibrosis and excellent long-term survival in many
      patients, whereas untreated patients may expect a 10-year survival of < 30%. The
      use of azathioprine monotherapy (2 mg/kg/day) has gained widespread acceptance in
      maintaining remission in clinical practice. Although all patients with autoimmune
      hepatitis may not need treatment, particularly those with mild disease,
      alternative strategies are required in patients who have failed to achieve
      remission on standard therapy of steroids with or without azathioprine, or
      patients with azathioprine-induced drug toxicity. In such circumstances, the use
      of salvage therapy in the form of ciclosporin, tacrolimus or mycophenolate
      mofetil may be warranted. Liver transplantation is the treatment of choice for
      patients who present with subacute liver failure or decompensated cirrhosis.
      Salvage therapy results in an exponential rise in cost with each increment in
      therapeutic escalation. As an alternative to standard therapy, it has also been
      suggested that novel therapies such as ciclosporin, tacrolimus or mycophenolate
      mofetil be initiated to achieve remission. However, a > 10-fold cost differential
      exists between the charges associated with more potent immunosuppression and
      standard therapy. Therefore, in evaluating novel immunosuppression in autoimmune
      hepatitis, it behoves clinicians not only to consider end points pertaining to
      efficacy, but also end points pertaining to cost-effectiveness. Moreover, the
      exact role of pharmacogenomics and genotyping of thiopurine methyltransferase in
      patients with autoimmune hepatitis needs to be fully defined.

PMID- 16433581
TI  - Cost-effectiveness of moderate-to-severe psoriasis treatment.
AB  - Psoriasis is a common, chronic inflammatory disease that can cause as much
      disability as cancer, diabetes or other major medical illnesses. Traditional
      therapies for treating moderate-to-severe psoriasis include phototherapy,
      methotrexate, oral retinoids and ciclosporin. New biological treatments provide
      further therapeutic options, but add to the already considerable cost of managing
      psoriasis. Expert panels have published guidelines for the use of biological
      agents in managing moderate-to-severe psoriasis; however, few if any of these
      guidelines appropriately consider the cost-effectiveness of treatment options.
      When considering cost-effectiveness in addition to safety and efficacy,
      ultraviolet Type B phototherapy seems to be the best first-line agent for the
      control of moderate-to-severe psoriasis, despite a small potential for cumulative
      toxicity. The biologics should be considered as second-line agents alongside the
      traditional systemic treatments when phototherapy proves to be ineffective or is
      otherwise contraindicated, such as in patients with psoriatic arthritis.

PMID- 16433582
TI  - The role of proton pump inhibitors in the treatment of Zollinger-Ellison
      syndrome.
AB  - Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease,
      diarrhoea and gastric acid hypersecretion associated with a gastrin-secreting
      tumour. The incidence is unknown, but, in the US, the frequency is 0.1-3.0
      million people. Zollinger-Ellison syndrome is associated with multiple endocrine
      neoplasia type 1 in 25-35% of the cases. The diagnosis of Zollinger-Ellison
      syndrome is suggested when plasma gastrin is > 1000 pg/ml and the basal acid
      output is > 15 mEq/h or when associated with a pH < 2. The treatment is focused
      on controlling gastric acid hypersecretion and localisation of the tumour and its
      metastases. Proton pump inhibitors are the most effective antisecretory drugs and
      can be administered at high dosages. This review focuses on the role of the
      proton pump inhibitors in the management of gastric acid hypersecretion in
      Zollinger-Ellison syndrome.

PMID- 16433583
TI  - A review of erlotinib and its clinical use.
AB  - Erlotinib is an orally available, reversible tyrosine kinase inhibitor of the
      epidermal growth factor receptor. Encouraging activity as a single agent and in
      combination with other targeted agents has been demonstrated in Phase II trials
      in many tumour types. Erlotinib has an established role in the treatment of
      advanced, refractory non-small cell lung cancer-based on a pivotal trial
      demonstrating a survival advantage over best supportive care. In a Phase III
      trial, the addition of erlotinib to gemcitabine improved survival in advanced
      pancreatic cancer. The toxicity profile of erlotinib includes diarrhoea and rash,
      with no haematological side effects. Predictive factors for response include the
      presence of a rash, epidermal growth factor receptor expression and mutation
      status. This article reviews the current clinical status of erlotinib.

PMID- 16433584
TI  - Thalidomide in multiple myeloma.
AB  - Multiple myeloma is an incurable bone marrow cancer, the treatment of which is
      notoriously difficult. Only modest advances have been achieved using complex
      polychemotherapeutic regimens, transplant strategies and supportive therapy. In
      1999, when new drugs for myeloma were urgently needed, thalidomide was introduced
      and opened up a completely new line of therapy for the disease. Although the
      mechanism of action is not yet completely understood, thalidomide has
      demonstrated efficacy in patients with refractory, relapsed myeloma, even in late
      stage cases. This article reviews the current knowledge of thalidomide in myeloma
      treatment, focusing especially on the possible mechanisms of action, clinical
      results and adverse events of this drug.

PMID- 16433585
TI  - Duloxetine in diabetic neuropathy.
AB  - Duloxetine is a balanced serotonin noradrenaline re-uptake inhibitor that has
      recently become the first agent to receive regulatory approval for the treatment
      of painful diabetic neuropathy in the US. This compound has no other significant
      receptor or channel activities other than the serotonin and noradrenaline re
      uptake inhibition mechanisms and works to diminish or control the symptoms of
      diabetic neuropathy. Duloxetine has no known neuroprotective or other effects
      that prevent the development of neuropathy in patients with diabetes. Its
      effectiveness in diabetic neuropathy confirms the proposed role of serotonin and
      noradrenaline as key mediators of the descending pain inhibition pathways of the
      brain stem and spinal cord. Clinical studies have demonstrated the high degree of
      safety and efficacy for the compound with no adverse effects on glycaemic control
      due to the action of duloxetine being identified.

PMID- 16433586
TI  - Sirolimus- or paclitaxel-eluting stents for coronary artery revascularisation.

PMID- 16433587
TI  - 6th International Workshop on Clinical Pharmacology of HIV Therapy.
AB  - The 6th International Workshop on Clinical Pharmacology of HIV Therapy convened
      at the Fairmont Le Chateau Frontenac in Quebec, Canada on April 28-30, 2005. More
      than 170 participants registered for this workshop, demonstrating the continued
      interest in exploring and understanding the complexities of antiretroviral
      pharmacology. The purpose of this meeting was to present and discuss research
      related to antiretroviral pharmacokinetics, pharmacodynamics, drug interactions,
      therapeutic drug monitoring and the assays necessary for measuring antiretroviral
      concentrations. This article highlights some of the 22 oral and 98 poster
      presentations that were presented at this meeting.

PMID- 16433588
TI  - What are we looking for in new antibacterials and how do we design it?
AB  - The need for new antibacterial agents is a pressing, unmet medical need, but
      success has been limited, resulting in decreased business interest. Part of the
      problem is the lack of clarity regarding what would make a new-generation
      'blockbuster' antibacterial and how this agent could be designed. To this end,
      the authors outline a few ideas regarding the changes in approach in order to
      accomplish these needs, including a fundamental change in the drug discovery
      process.

PMID- 16433589
TI  - Antiviral applications of RNAi for coronavirus.
AB  - Until the appearance of severe acute respiratory syndrome (SARS), caused by the
      SARS coronavirus (SARS-CoV) in early 2003, coronavirus infection was not
      considered to be serious enough to be controlled by either vaccination or
      specific antiviral therapy. It is now believed that the availability of antiviral
      drugs effective against SARS-CoV will be crucial for the control of future SARS
      outbreaks. Recently, RNA interference has been successfully used as a more
      specific and efficient method for gene silencing. RNA interference induced by
      small interfering RNA can inhibit the expression of viral antigens and so
      provides a new approach to the therapy of pathogenic viruses. This review
      provides an overview of current information on coronavirus and the application of
      small interfering RNA in viral therapeutics, with particular reference to SARS
      CoV.

PMID- 16433590
TI  - Inhibitors of cholesteryl ester transfer protein--a new approach to coronary
      artery disease.
AB  - Despite the use of the statins to lower low-density lipoprotein-cholesterol,
      leading to major reductions in the mortality and morbidity that is associated
      with coronary artery disease, considerable mortality and morbidity remains.
      Increasing high-density lipoprotein (HDL)-cholesterol levels has been associated
      with reduced coronary artery disease mortality and morbidity in several studies.
      Inhibition of cholesteryl ester transfer protein (CETP) activity leads to
      increased HDL-cholesterol. In cholesterol-fed rabbits, antibodies against CETP
      increased HDL-cholesterol and decreased atherosclerotic lesions. In healthy
      subjects with mild dyslipidaemia, the CETP inhibitors JTT-705 and torcetrapib
      increased HDL-cholesterol and decreased low-density lipoprotein-cholesterol.
      Increasing HDL-cholesterol with CETP inhibitors is a new approach to
      dyslipidaemia that requires further investigation, especially in patients who
      have coronary artery disease.

PMID- 16433591
TI  - Neuropharmacology and potential efficacy of new treatments for tobacco
      dependence.
AB  - This review considers some of the novel therapies that are under development for
      the treatment of tobacco dependence, outlines their efficacy in clinical studies
      and explains their mechanisms of action in terms of contemporary theories for the
      psychobiology of the dependence. It focuses on three treatments with differing
      mechanisms of action that are at different stages of clinical development. The
      first is varenicline, a partial agonist at the alpha4beta2 nicotinic receptors,
      which are thought to play a central role in the addiction to nicotine.
      Preclinically, this drug mimics the effects of nicotine on dopamine (DA) release
      in the nucleus accumbens when given alone but attenuates this response to a
      subsequent nicotine challenge and reduces nicotine self administration. Very
      encouraging results have been seen in the five clinical studies that have been
      reported with this drug. The second compound, rimonabant, is a cannabinoid CB1
      receptor antagonist. Preclinically, this compound reduces nicotine self
      administration, DA turnover in nucleus accumbens and attenuates reinstatement of
      nicotine-seeking behaviour. Clinically, the drug is well tolerated but its
      effects on smoking cessation are equivocal. However, it has the valuable
      additional property of inhibiting post-cessation weight gain. Nicotine 'vaccines'
      are the final group of treatments considered, which involves raising antibodies
      in the blood that limit the amount of nicotine that penetrates into the brain,
      thereby reducing the psychopharmacological responses to the drug. The vaccines
      also reduce DA turnover in nucleus accumbens and reinstatement of nicotine
      seeking behaviour after nicotine readministration. The three vaccines discussed
      are well tolerated and show signs of good efficacy; however, the increase in
      antibody titre, evoked by the treatment, shows significant inter-individual
      variation and is generally short lived. Thus, although this approach may provide
      a valuable aid to smoking cessation, it seems unlikely that it can be used for
      primary prevention.

PMID- 16433592
TI  - Targeting the proteasome as a therapeutic strategy against haematological
      malignancies.
AB  - The ubiquitin-proteasome pathway is responsible for the vast majority of
      regulated eukaryotic intracellular proteolysis. Inhibition of the proteasome
      induces beneficial antitumour effects by blocking cell-cycle progression,
      inducing apoptosis and suppressing angiogenesis. Bortezomib is the first
      proteasome inhibitor to reach the clinical arena, where Phase I - III trials
      verified its activity against relapsed/refractory multiple myeloma. Testing is
      ongoing to determine bortezomib's role in front-line therapy of this plasma cell
      dyscrasia, as well as in non-Hodgkin's lymphoma, in which encouraging single
      agent activity has been seen. Proteasome inhibition is also a rational strategy
      to overcome chemoresistance and induce chemosensitisation. Combinations of
      bortezomib and other agents have enhanced efficacy, and additional studies are
      probing the activity of several regimens in lymphoid and myeloid malignancies.
      The current state of knowledge about the activity of bortezomib, both alone and
      in combination with standard chemotherapeutics, as part of the emerging
      armamentarium against haematological malignancies is reviewed.

PMID- 16433593
TI  - Recent developments in the systemic therapy of advanced gastroesophageal
      malignancies.
AB  - Cancers of the upper gastrointestinal tract are a common cause of worldwide
      morbidity and mortality. The prognosis for patients with these cancers remains
      poor and only a minority of patients are cured. Systemic therapy has been used to
      treat patients with advanced disease but outcomes have not improved dramatically
      in the past few decades. Newer, more effective agents are desperately needed, and
      agents such as the taxanes (docetaxel and paclitaxel), irinotecan, oxaliplatin
      and capecitabine have recently shown some promise. In addition, molecularly
      targeted, non-cytotoxic therapies are being evaluated with the hope of improving
      the available therapeutic options. This article reviews the current clinical data
      regarding systemic therapy for patients with advanced upper gastrointestinal
      malignancies.

PMID- 16433594
TI  - Tigecycline for the treatment of infections due to resistant Gram-positive
      organisms.
AB  - Tigecycline is a novel compound in the antimicrobial class known as the
      glycylcyclines. In vitro studies have shown it to have activity against the vast
      majority of Gram-positive pathogens, including multi-drug resistant
      Staphylococcus aureus and vancomycin-resistant enterococci. Tigecycline has also
      shown excellent in vitro activity against a broad range of Gram-negative enteric
      organisms including strains resistant to other antimicrobials as well as
      anaerobes. Tigecycline is not affected by the ribosomal protection and efflux
      mechanisms transmitted by the known tetracycline resistance genes. Tigecycline
      represents an exciting new class of glycylcycline antimicrobial agents for the
      treatment of multi-drug resistant Gram-positive bacteria. Although its broad
      spectrum of activity, which also includes Gram-negative enterics, makes it a
      candidate for empiric therapy for intra-abdominal infections, its spectrum
      against multi-drug resistant Gram-positive organisms makes it a very attractive
      choice for empiric treatment of Gram-positive infections in patients at risk for
      resistant strains. The two pivotal Phase II clinical trials involving complicated
      skin and soft tissue infections and intra-abdominal infections have shown the
      drug to be safe and effective.

PMID- 16433595
TI  - Anecortave acetate.
AB  - This manuscript reviews the pharmacotherapeutics of the novel, angiostatic
      cortisene, anecortave acetate suspension, for the treatment of age-related
      macular degeneration. The chemistry, pharmacokinetics and pharmacodynamics of
      anecortave acetate are discussed, and the results of the multi-centre,
      randomised, controlled clinical trials for the treatment of subfoveal choroidal
      neovascularisation in age-related macular degeneration summarised. It also
      discusses ongoing clinical trials involving anecortave acetate for dry and wet
      age-related macular degeneration.

PMID- 16433596
TI  - Current therapeutic uses of lenalidomide in multiple myeloma.
AB  - Thalidomide has demonstrated a broad spectrum of pharmacological and
      immunological effects, with potential therapeutic applications that span a wide
      spectrum of diseases: cancer and related conditions; infectious diseases;
      autoimmune diseases; dermatological diseases; and other disorders such as
      sarcoidosis, macular degeneration and diabetic retinopathy. Immunomodulatory
      derivative lenalidomide has more potent antitumour and anti-inflammatory effects.
      The molecular mechanisms of antitumour activity of lenalidomide have been
      extensively studied in multiple myeloma (MM). It directly induces growth arrest
      and/or apoptosis of even drug-resistant MM cells; inhibits binding of MM cells to
      bone marrow extracellular matrix proteins and stromal cells; modulates cytokine
      secretion and inhibits angiogenesis in the bone marrow milieu; and augments host
      antitumour immunity. Importantly, lenalidomide induces significant clinical
      responses even in patients with relapsed/refractory MM. Therefore, lenalidomide
      represents a new class of antitumour agents that is useful in the treatment of
      MM. Lenalidomide has received fast track designation from the FDA for the
      treatment of MM and myelodysplastic syndromes.

PMID- 16433598
TI  - 15th Annual Congress of European Respiratory Society.
AB  - The 15th Annual Congress of the European Respiratory Society was held in
      Copenhagen on 17 - 21 September 2005. The congress was attended by > 16,000
      delegates from 119 countries. The meeting covered a wide range of issues
      (epidemiological, pathological and therapeutic) relating to the spectrum of
      respiratory diseases. The following summary refers to aspects of the more
      frequently encountered disorders of asthma and chronic obstructive pulmonary
      disease where new information was presented related to clinical development for
      projects including smoking cessation, combination therapies and new diagnostic
      approaches.

PMID- 16433597
TI  - Infliximab for chronic obstructive pulmonary disease: towards a more specific
      inflammation targeting?
AB  - Chronic obstructive pulmonary disease (COPD) is a predominantly smoking-related
      condition in which chronic progressive airways obstruction results because of
      inflammation that is triggered and maintained by the causative agent and enhanced
      during exacerbations. Inflammation is dominated by neutrophils, and macrophages
      and their mediators. TNF-alpha is a proinflammatory cytokine involved in COPD
      pathogenesis. Treatment of the stable disease is mainly inhalatory with
      anticholinergics, beta(2) agonsists and inhaled corticosteroids being involved in
      various stages of the disease. Novel therapeutic agents are currently under
      investigation for COPD treatment and some of them target various inflammation
      mediators. Infliximab is a monoclonal anti-TNF-alpha antibody with demonstrated
      efficacy in other autoimmune diseases, such as Crohn's disease and rheumatoid
      arthritis. The current study assesses the scientific rationale for the use of
      infliximab in COPD patients.

PMID- 16433600
TI  - Bird flu redux.

PMID- 16433602
TI  - Capillary activity of surgical sutures and suture-dependent bacterial transport:
      a qualitative study.
AB  - OBJECTIVE: To evaluate the multitude of new synthetic absorbable sutures (both
      monofilament and multifilament) in comparison with older materials with regard to
      capillarity and bacterial transport. METHODS: Sutures of United States
      Pharmacopoeia (USP) 4-0 thickness were arranged in a three-chamber system under
      sterile conditions. Either a colorant (liquid transport evaluation) or bacteria
      (bacterial transport evaluation) were added to the contamination chamber, and
      movement of colorant or bacteria was evaluated for as long as 30 days. RESULTS:
      None of the monofilament sutures transported colorant or bacteria. Colorant
      transport was found on the pseudomonofilament and multifilament sutures between
      the first and the fifth day. Escherichia coli were transported on the majority of
      the multifilament sutures, although no transport was found on silk or polyester
      sutures. Bacterial transport was most often evident in tests using the motile
      Proteus mirabilis. CONCLUSIONS: All multifilament and pseudomonofilament suture
      designs allowed transport of colorants and bacteria to some degree. The movement
      of fluids and bacteria did not depend on the absorptive capacity of the sutures,
      coating, or the presence of an open suture end.

PMID- 16433601
TI  - The effect of antipyretic therapy upon outcomes in critically ill patients: a
      randomized, prospective study.
AB  - BACKGROUND: Despite the large body of evidence suggesting a beneficial role of
      fever in the host response, antipyretic therapy is commonly employed for febrile
      critically ill patients. Our objective was to evaluate the impact of antipyretic
      therapy strategies on the outcomes of critically ill patients. METHODS: Patients
      admitted to the Trauma Intensive Care Unit over a nine-month period were eligible
      for inclusion, except those with traumatic brain injury. Patients were randomized
      on day three of the ICU stay into aggressive or permissive groups. The aggressive
      group received acetaminophen 650 mg every 6 h for temperature of >38.5 degrees C
      and a cooling blanket was added for temperature of >39.5 degrees C. The
      permissive group received no treatment for temperature of >38.5 degrees C, but
      instead had treatment initiated at temperature of >40 degrees C, at which time
      acetaminophen and cooling blankets were used until temperature was <40 degrees C.
      Patient demographics, daily temperatures, systemic inflammatory response syndrome
      (SIRS) scores, multiple organ dysfunction syndrome (MODS) scores, and infections
      and complications were recorded. RESULTS: Between December, 2002 and September,
      2003, 572 patients were screened, of whom 82 met criteria for enrollment. Forty
      four patients were randomized to the aggressive group and 38 patients were
      randomized to the permissive group for a total of 961 and 751 ICU days,
      respectively. There were 131 infections in the aggressive group and 85 infections
      in the permissive group (4 +/- 6 vs. 3 +/- 2 infections per patient, p = 0.26).
      There were seven deaths in the aggressive group and only one death in the
      permissive group (p = 0.06, Fisher Exact Test). The study was stopped after the
      first interim analysis due to the mortality difference, related to the issues of
      waiver of consent and the mandate for minimal risk. CONCLUSIONS: Aggressively
      treating fever in critically ill patients may lead to a higher mortality rate.

PMID- 16433604
TI  - A murine model of invasive aspergillosis: variable benefit of interferon-gamma
      administration under in vitro and in vivo conditions.
AB  - BACKGROUND: Interferon-gamma modulates host defense in a number of infectious
      diseases. Previous studies have shown that systemic administration of interferon
      gamma (IFN-gamma) can enhance survival in experimental invasive aspergillosis
      (IA). METHODS: Using a novel model of murine IA that is characterized by primary
      pulmonary infection, we investigated the role of IFN-gamma in the phagocytosis
      and killing of Aspergillus fumigatus by murine neutrophils and pulmonary alveolar
      macrophages in vitro and the impact of systemic and regional administration of
      IFN-gamma on the course of IA in glucocorticoid-treated mice. RESULTS: In vitro,
      IFN-gamma significantly enhanced phagocytosis and killing function of both
      neutrophils and alveolar macrophages from normal animals, but not cortisone
      treated animals. In vivo, intravenous administration of IFN-gamma did not improve
      phagocyte recruitment, in vivo killing, or mortality from IA. Regional
      (intranasal) administration of IFN-gamma to the lungs enhanced recruitment of
      phagocytic cells to the lungs and improved in vivo killing, but did not alter
      (and actually worsened) mortality from IA. CONCLUSIONS: The in vitro and in vivo
      effects of IFN-gamma in IA are contingent on many variables, including the route
      of administration and the specific pathogenesis of infection.

PMID- 16433603
TI  - Efficacy of double gloving with an intrinsic indicator system.
AB  - BACKGROUND: Blood-borne infection is an ever-present fear for medical
      professionals, especially surgeons and operating room personnel. Safety is
      paramount, and the reliability and efficacy of surgical gloves are crucial, as
      gloves are the most important barriers protecting hospital personnel and
      patients. Unfortunately, glove perforation rates are as high as 78% in high-risk
      procedures. As well as being efficacious, surgical gloves must be comfortable and
      easy to don, and when holes are present, it is imperative they be detected
      expeditiously. The purpose of this double-blind randomized study was to evaluate
      the ability of participants to locate 30-micron laser holes in surgical gloves
      while performing simulated surgery and to evaluate the Biogel Indicator Glove
      System, which reveals punctures. METHODS: Twenty glove configurations (eight
      single, twelve double) were tested, half of which had laser-created holes. Each
      of the 25 participants tested and evaluated 20 configurations randomly. Simulated
      surgery terminated when a hole was identified by the participant or at the end of
      two minutes, whichever occurred first. Participants also rated their perceptions
      of each glove's features on questionnaires, all of which were returned, with
      95.8% being complete. RESULTS: Participants found 84% and 56% of the holes in the
      two indicator systems, latex and synthetic, in an average of 22 seconds and 42
      seconds, respectively. In the worst-performing latex and synthetic glove
      configurations, participants found only 8% and 12% of the holes at an average of
      47 seconds and 67 seconds, respectively. Indicator gloves were highly rated for
      comfort and ease of use. CONCLUSIONS: Double gloving with an indicator system
      provides the best protection and allows the timeliest identification of
      perforations. Participants failed to identify most of the holes in the non
      indicator gloves.

PMID- 16433605
TI  - Abdominal complications of ventricular assist device placement.
AB  - BACKGROUND: Ventricular assist devices (VADs) provide a bridge to transplantation
      for patients awaiting heart transplant. Because of its intra-abdominal placement,
      the potential exists for major abdominal complications. The purpose of this study
      is to identify VAD-associated abdominal complications and their incidence, and to
      describe preventive measures. METHODS: Records of patients having had VAD
      placement were identified from our registry from April 12, 1995, when the first
      VAD placement occurred, to July 15, 2003. Each patient was evaluated for the
      occurrence of an abdominal complication, defined as mechanical small bowel
      obstruction, infection with an abdominal source, hernia, or other abdominal
      pathology occurring after VAD placement. RESULTS: One hundred twenty-four VADs
      were implanted in 100 patients. Of these patients, 82 received one VAD, 13
      received two devices, four received three devices, and one patient received four
      devices. Twelve abdominal complications occurred in 11 patients (11%). There was
      a 36% (4/11) pre-transplant mortality rate in patients with an abdominal
      complication, compared to 17% (15/89) pre-transplant mortality in patients
      without an abdominal complication (p = 0.21). Three of five patients with
      abdominal infection died. CONCLUSIONS: Abdominal complications after VAD
      placement are common. Intra-abdominal VAD infection is the most common and
      serious complication, leading to a mortality rate of 60% in our population.
      Additionally, small bowel obstructions, incisional and inguinal hernias,
      acalculous cholecystitis, and pancreatitis also occurred. Appropriate preventive
      measures may decrease the risk of developing many of these complications.

PMID- 16433606
TI  - Pharmacodynamic modeling of imipenem-cilastatin, meropenem, and piperacillin
      tazobactam for empiric therapy of skin and soft tissue infections: a report from
      the OPTAMA Program.
AB  - BACKGROUND: The bactericidal exposures necessary for positive clinical outcomes
      among skin and soft tissue infections are largely dependent on interpatient
      pharmacokinetic variability and pathogen drug susceptibility. By simulating the
      probability of achieving target bactericidal exposures, the pharmacodynamics of
      three beta-lactam agents were compared against a range of pathogens implicated
      commonly in complicated skin and soft tissue infections. METHODS: Using Monte
      Carlo simulation, pharmacodynamic target attainment expressed as the percentage
      of the time interval during which the antibiotic concentration exceeded the
      minimal inhibitory concentration (%T > MIC) in serum and blister fluid was
      calculated for 5,000 simulated patients receiving imipenem-cilastatin 0.5 g q8h,
      meropenem 0.5 g q8h, piperacillin-tazobactam 3.375 g q6h, and piperacillin
      tazobactam 4.5 g q8h. The pharmacokinetics for each antibiotic were derived from
      previously published healthy volunteer studies. The MICs for Staphylococcus
      aureus, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sp., Klebsiella
      sp., coagulase-negative staphylococci, Proteus sp., beta-hemolytic streptococci,
      and Serratia sp. were taken from the MYSTIC 2003 surveillance study and weighted
      by the prevalence of each pathogen among 1,404 isolates collected from skin and
      soft tissue infections during the 2000 SENTRY study. The prevalence of
      methicillin-resistant Staphylococcus aureus (MRSA) was added into the model at
      increasing resistance rates. RESULTS: Imipenem-cilastatin, meropenem, and
      piperacillin-tazobactam 3.375 g q6h achieved greater than 90% likelihood of
      achieving bactericidal exposure in serum and blister fluid until the prevalence
      of MRSA increased beyond 10%. Piperacillin-tazobactam 4.5 g q8h achieved a lower
      probability of achieving bactericidal exposure than the other regimens (88.7%, p
      < 0.001). CONCLUSIONS: When the incidence of MRSA is low, imipenem-cilastatin,
      meropenem and piperacillin-tazobactam 3.375 g q6h would be optimal choices for
      the empiric treatment of complicated skin and soft tissue infections among the
      regimens studied. When MRSA is suspected, a drug that retains activity against
      this pathogen should be considered.

PMID- 16433607
TI  - The impact of diabetes in patients with necrotizing soft tissue infections.
AB  - BACKGROUND: Given the association of diabetes with necrotizing soft tissue
      infections (NSTIs) and hyperglycemia with mortality in critically ill patients,
      this study investigates the impact of diabetes and hyperglycemia in NSTI
      patients. METHODS: This is a retrospective review of NSTI patients at LBJ General
      Hospital between January 1995 and December 2002, assessing infectious morbidity,
      mortality, and length of hospital stay. RESULTS: There was a trend towards
      increased infectious complications, defined as a hospital-acquired (not present
      within 48 h of presentation) infection at a secondary site, amongst diabetic
      patients (RR 2.1, 95% CI 0.7-6.8) and patients with admission hyperglycemia
      greater than 200 mg/dL (OR 1.9, 95% CI 0.7-5.7) but not with admission
      hyperglycemia greater than 120 mg/dL (OR 1.6, 95% CI 0.3-8.7). Patients with an
      infectious complication had a longer hospital stay (median, interquartile range
      [IQR]; 36, 30-44 days vs. 10, 7-20 days, p < 0.001), increased mortality (29% vs.
      7%, p = 0.05), and poorer outcome defined as death, amputation, or hospital stay
      exceeding the 75th percentile for length of stay (79% vs. 20%, p < 0.001).
      CONCLUSIONS: Diabetes mellitus and admission hyperglycemia may increase
      infectious complications in NSTI patients, predicting a longer and more
      complicated hospital course. Further study is required to define the optimal
      metabolic target in this patient population.

PMID- 16433608
TI  - In vitro susceptibilities of aerobic and facultative gram-negative bacilli
      isolated from patients with intra-abdominal infections worldwide: the 2002 Study
      for Monitoring Antimicrobial Resistance Trends (SMART).
AB  - BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) was
      begun in 2002 to monitor international drug-resistance patterns among aerobic and
      facultative gram-negative bacilli isolated from patients with intra-abdominal
      infections. METHODS: In 2002, 40 medical centers from 17 countries collected
      consecutive non-duplicate isolates from intra-abdominal infections for
      susceptibility testing against 12 antimicrobial agents using the broth
      microdilution methods recommended by the Clinical and Laboratory Standards
      Institute (formerly the National Committee for Clinical Laboratory Standards).
      RESULTS: A total of 3,134 aerobic and facultative gram-negative bacilli were
      isolated. Enterobacteriaceae accounted for 82% of the total and were most
      consistently susceptible to amikacin and the carbapenems. Escherichia coli (45%)
      and Klebsiella spp. (17%) were the most common species. The susceptibility rates
      of these organisms to the 12 antimicrobial agents differed among geographic
      regions, with isolates from the Asia/Pacific and Latin American regions usually
      having the highest rates of resistance. Ampicillin/sulbactam was the agent least
      frequently active against E. coli (56% susceptible) and Klebsiella spp. (73%
      susceptible). Extended-spectrum beta-lactamases (ESBLs) were detected
      phenotypically in 7% of E. coli, 13% of Klebsiella spp., and 18% of Enterobacter
      spp. Producers of ESBL overall had a more antibiotic-resistant profile than non
      producers but were usually susceptible to carbapenems. CONCLUSIONS: Antimicrobial
      resistance rates among gram-negative bacilli isolated from intra-abdominal
      infections differed among geographic regions. The carbapenems were consistently
      active in vitro against Enterobacteriaceae worldwide, including ESBL producers.

PMID- 16433609
TI  - Postcholecystectomy surgical site infection by Salmonella enterica var.
      Weltevreden.
AB  - BACKGROUND: Surgical site infections (SSI) are the most common complication of
      gastrointestinal surgery. The most common endogenous organisms encountered are
      the enteric pathogens. METHODS: We report a rare case of S. enterica var.
      Weltevreden as a cause of SSI after cholecystectomy and common bile duct
      exploration. Pertinent literature is reviewed. RESULTS: The infection was due to
      bile spillage and contamination during surgery. The organism was found to be
      sensitive only to imipenem, and the patient recovered following intravenous
      treatment with that carbapenem. CONCLUSIONS: This case illustrates the fact that
      cholecystectomy with bile spillage is a definite risk factor for SSI. Although
      controversial, isolation of the pathogen from the bile and the surgical site must
      be made to allow this rare pathogen to be identified. Appropriate antibiotic
      could then be directed against the pathogen.

PMID- 16433615
TI  - Transdifferentiation wars.

PMID- 16433616
TI  - Focusing of gene expression as the basis of stem cell differentiation.
AB  - In a prior report (Stem Cells Dev 14(4):354-366, 2005), we employed two
      dimensional gel electrophoresis followed by advanced proteomics and the Database
      for Annotation, Visualization and Integrated Discovery (DAVID) to compare the
      protein expression profiles of mesenchymal stem cells to that of fully
      differentiated osteoblasts. These data were reported to advance technical
      approaches to define the basis of differentiation, but also led us to suggest
      that osteogenic differentiation of stem cells may result from the focusing of
      gene expression in functional clusters (e.g., calcium-regulated signaling
      proteins or adherence proteins) rather than simply from the induced expression of
      new genes, as many have assumed. Here, we have employed these analytical
      techniques to compare protein expression by mesenchymal stem cells directly with
      that of cells derived from them after induced osteogenic differentiation. Our
      results support the concept of gene focusing as the basis of differentiation.
      Specifically, induced differentiation results in a decrease in the number of
      mesenchymal cell markers and calcium-mediated signaling molecules expressed by
      their differentiated progeny. This effect was seen in parallel to increased
      expression of specific extracellular matrix (ECM) molecules and their receptors.
      These results strongly imply that changes in the ECM have a direct impact on stem
      cell differentiation, and that osteogenic differentiation of stem cells directed
      by matrix clues results from focusing of the expression of genes involved in Ca2+
      dependent signaling pathways.

PMID- 16433617
TI  - Insulin-like growth factor-I induces early osteoblast gene expression in human
      mesenchymal stem cells.
AB  - Human adult mesenchymal stem cells (hMSCs) differentiate into an osteogenic
      lineage if the appropriate differentiative cues, such as dexamethasone or bone
      morphogenetic protein 2 (BMP-2), are present. This study was undertaken to
      determine the role of insulin-like growth factor I (IGFI) in the regulation of
      early osteoblast differentiation in hMSC. Previous studies have shown that IGF-I,
      regulates bone formation and remodeling by participating in the differentiation
      of mature cells of osteoblast lineage. We hypothesized that IGF-I exerted its
      effects early, but the effects were too subtle to be detected. Therefore,
      engineered hMSCs to produce IGF-I via adenoviral transfection and used
      quantitative real-time PCR (qPCR) to assess marker gene expression. Here we show
      that IGF-I up-regulates Type I collagen, Runx2, and alkaline phosphatase (Alp)
      gene expression in hMSCs, genes indicative of early osteogenic differentiation.
      We also observed mineral deposition in the absence of dexamethasone (Dex) in hMSC
      cultures treated with recombinant human BMP-2 after transduction with Ad-IGF-I.
      In conclusion Igf-I transduction up-regulated markers of osteoblastic
      differentiation and in conjunction with recombinant BMP-2-induced matrix
      mineralization independently of Dex (see Salasznyk et al., Stem Cells Dev
      14(6):608-620, 2005, this issue).

PMID- 16433618
TI  - Substrate induction of osteogenesis from marrow-derived mesenchymal precursors.
AB  - Therapeutic modalities aimed at bone regeneration are increasingly employing
      extracellular matrix (ECM) constituents to control bone marrow progenitor cell
      (BMPC) commitment, growth, and differentiation. However, the precise role these
      ECM elements play during stem cell differentiation remains unclear. (See also
      Salaszynk et al., Stem Cells Dev 14(6):608-620, 2005; and Schwartz et al., Stem
      Cells Dev. 14(6), 643-655, 2005, both in this issue.) Because bone formation
      ultimately begins with the recruitment and commitment of BMPCs into the
      osteogenic lineage, factors that enhance this process are clearly therapeutic
      targets. We hypothesized that BMPC attachment, proliferation, and osteogenic
      differentiation would be potentiated when cultured on ECM proteins normally found
      in the bone niche. To examine this, we cultured murine BMPCs on laminin-1,
      fibronectin, and collagen type-1 substrates for up to 14 days and assessed their
      homogeneity, attachment, proliferation, and expression of the specific bone
      lineage markers RUNX2, collagen-1, alkaline phosphatase, and osteocalcin. We
      found that freshly harvested mBMPCs contain a mixed population of progenitor
      cells and that the mesenchymal pool can be enriched by adherent culture in the
      presence of leucine methyl ester. Furthermore, mBMPCs attached to laminin,
      fibronectin, and collagen-1 with varying affinity up to 3 h
      (fibronectin>or=collagen>laminin), after which time no difference could be
      detected. Despite this, growth was unaffected; cells thereafter proliferated
      equally well on all substrates up to confluence (7 days). Notably, commitment to
      the osteoblast lineage (RUNX2) increased up to 14 days for cells cultured on the
      various substrates, yet no difference was observed at day 14 in the expression of
      collagen-1, alkaline phosphatase, or osteocalcin. We conclude that mBMPC
      differentiation down the osteoblastic lineage is time-dependent in osteogenic
      culture and that attachment to ECM matrices potentiates lineage commitment rather
      than growth.

PMID- 16433619
TI  - Defined conditions for development of functional hepatic cells from human
      embryonic stem cells.
AB  - Human embryonic stem (hES) cells provide an important means to evaluate specific
      soluble and cell-bound stimuli that regulate development of specific cell
      lineages. Here, we examined specific cytokines and extracellular matrix (ECM)
      proteins that support differentiation of hES cells to hepatocytes. Tests of
      several different conditions determined that addition of fibroblast growth factor
      (FGF)-4 and hepatocyte growth factor in completely serum-free cultures of hES
      cell-derived embryoid bodies subsequently allowed to attach to type I collagen
      coated dishes led to maximal differentiation into cells, not only with the
      morphologic and phenotypic characteristics of hepatocytes but also the functional
      characteristics. Expression of common hepatic transcription factors including HNF
      3beta, HNF-1, and GATA-4 were all significantly induced under these conditions.
      Hepatocyte function was demonstrated by multiple complementary criteria:
      production of urea and albumin, phenobarbital-induced cytochrome P450 expression,
      and uptake of indocyanine green. These hES cell-derived hepatocytes will serve as
      a resource to understand normal human hepatocyte development and for applications
      such as cell replacement therapies and screening of pharmacologic drugs.

PMID- 16433620
TI  - Mixl1 and oct4 proteins are transiently co-expressed in differentiating mouse and
      human embryonic stem cells.
AB  - Embryonic stem cells (ESCs) have the capacity to form all the tissues in the body
      and hence, directed differentiation of ESCs along specific lineages represents a
      means to generate therapeutically useful cell types. It has been postulated that,
      during in vitro differentiation, ES cells sequentially pass through similar
      developmental stages as cells in the embryo. The availability of reagents that
      identify these stages would facilitate the monitoring and optimization of ESC
      differentiation. One key stage, the development of endodermal and mesodermal
      precursors in the early embryo, is marked by the transient expression of the
      transcription factor, Mixl1 and the stem cell gene, Oct4. In order to identify
      corresponding cells during ESC differentiation, we generated monoclonal
      antibodies to the Mixl1 protein that robustly detected both mouse and human
      proteins. Intracellular flow cytometry was used to show that approximately 90% of
      differentiating mouse ESCs transiently co-expressed Oct4 and Mixl1 proteins and
      that a subset of differentiating human ES cells also coexpressed MIXL1 and OCT4
      proteins. These experiments have demonstrated for the first time by protein
      expression that both human and mouse ESCs passed through developmental stages
      during in vitro differentiation that corresponded to those observed in early
      mammalian development. Furthermore, these studies confirmed that anti-Mixl1
      antibodies are a valuable reagent for monitoring ESC differentiation and will
      facilitate the efficient generation of clinically relevant cell types.

PMID- 16433621
TI  - Expression of the Gas7 gene and Oct4 in embryonic stem cells of mice.
AB  - Oct4 is a stem cell expression marker, and persistence of its expression retains
      pluripotency in embryonic stem (ES) cells. Our results indicate a pattern of
      gradual decrease in Oct4 expression, which is prominent in the blastocyst and
      markedly reduced in the gastrula and neurula. The presence of POU transcription
      factor-like domain in Gas7 prompted us to look for its expression in the early
      embryonic cells. We have observed high expression of the Gas7 protein in
      blastocysts that gradually decreased in the neurula stages. The localization of
      Gas7 was initially seen throughout the blastocyst, but was later confined to
      dorsal ectodermal regions of the neurula, conforming with its role in neuronal
      differentiation. Our data reveal that Gas7 might play a role in cellular
      migration and cell protection in the ES cells of mouse embryo.

PMID- 16433623
TI  - Cardiomyogenic potential of mesenchymal progenitors derived from human
      circulating CD14+ monocytes.
AB  - Previously, we reported a unique CD14+CD45+CD34+type I collagen+ cell fraction
      derived from human circulating CD14+ monocytes, named monocyte-derived
      mesenchymal progenitors (MOMPs). These primitive cells differentiate along
      mesenchymal lineages, including bone, cartilage, fat, and skeletal muscle. Here,
      we demonstrate that CD14+ monocytes generate MOMPs that differentiate into
      cardiomyocytes. MOMPs labeled with a fluorescent marker and co-cultivated with
      rat cardiomyocytes for 4 weeks expressed the cardiomyocyte-specific transcription
      factors Nkx2.5, GATA-4, eHAND, and MEF2 and the hematopoietic/monocytic markers
      CD45 and CD14 within 10 days and retained their proliferative capacity for up to
      16 days. A subpopulation of MOMPs subsequently expressed the cardiomyocyte
      specific markers micro-sarcomeric actinin, troponin I, and atrial natriuretic
      peptide on day 21. Furthermore, fluorescence-labeled, spontaneously beating cells
      that formed gap junctions with adjacent rat cardiomyocytes appeared in these
      cultures and these cells exhibited electrophysiological properties typical of
      ventricular myocytes. The co-cultivation of human MOMPs with rat GFP-tagged
      cardiomyocytes resulted in the generation of human cardiomyocytes lacking green
      fluorescent protein (GFP) staining, suggesting that our observations could not
      solely be explained by cell fusion. Our results demonstrate for the first time
      that human circulating CD14+ monocytes include progenitors capable of
      proliferating and differentiating along the cardiomyogenic lineage via their
      differentiation into MOMPs.

PMID- 16433622
TI  - Derivation of adipocytes from human embryonic stem cells.
AB  - Human embryonic stem (hES) cells are undifferentiated and pluripotent cells that
      hold great therapeutic potential, but are hampered by our limited knowledge to
      promote specific cell differentiation. Here we provide the first report of the
      directed differentiation of hES cells into adipocytes. Embryoid bodies (EBs)
      derived from hES cells are shown to respond to factors that promote adipogenesis.
      Differentiated cells were observed that displayed the key features of adipocytes,
      i.e., expression of specific molecular markers, such as peroxisome proliferator
      activated receptor gamma2 (PPARgamma2), adipocyte fatty acid binding protein
      (aP2) and adiponectin, the secretion of leptin, and the accumulation of lipid
      droplets in cytoplasm. Taken together, our results demonstrate that adipocytes
      derived from hES cells in vitro can provide a novel model system to study human
      adipogenesis and obesity.

PMID- 16433625
TI  - Transforming growth factor-beta induces differentiation of the labyrinthine
      trophoblast stem cell line SM10.
AB  - The mammalian placenta consists of different trophoblast cell types that assist
      in the variety of functions required for the maintenance of pregnancy. In
      rodents, labyrinthine trophoblasts of the placenta are especially important,
      because they are capable of differentiating into fused labyrinthine cells, which
      form the feto-maternal exchange surface. Even though the molecular signals
      triggering labyrinthine trophoblast differentiation are poorly understood,
      transforming growth factor-beta (TGF-beta) has been shown to be present in the
      placental environment and alter trophoblast development. In this study, we
      investigated the effects of TGF-beta on the differentiation of the labyrinthine
      trophoblast stem cell lines SM10 and HRP-1. RT-PCR analyses demonstrated that
      while the molecular expression of labyrinthine-specific lineage markers (Esx1,
      Tfeb, and Tec) was maintained in TGF-beta-treated SM10 and HRP-1 cells, TGF-beta
      induced the down-regulation of trophoblast stem cell markers Id2 and Cdx2. In
      contrast, TGF-beta induced the expression of a marker of differentiated
      labyrinthine trophoblasts, Gcm1, only in the SM10 cell line. Furthermore, we
      demonstrated an increased glucose uptake in the TGF-beta-treated SM10 cells,
      indicative of functional differentiation. Finally, cell fusion in TGF-beta
      treated SM10 and HRP-1 cells was investigated by western blotting analysis of
      placental alkaline phosphatase and cadherin-11 and by microscopic analyses of
      cell morphology using green fluorescent protein (GFP) and rhodamine phalloidin
      staining. The western blotting and morphological analyses indicate TGF-beta
      induced cell fusion and morphological differentiation in the SM10 cell line. The
      SM10 cell line will provide a new and unique model for detailed analysis of TGF
      beta-induced molecular events associated with labyrinthine trophoblast
      differentiation and function.

PMID- 16433624
TI  - Definitive hematopoiesis from acetyl LDL incorporating endothelial cells in the
      mouse embryo.
AB  - Previously, we reported generation of erythropoiesis from acetyl low-density
      lipoprotein (Ac-LDL)- incorporating endothelial cells (ECs) in the mouse embryo.
      However, it is still unclear whether the other types of definitive hematopoietic
      cells (HCs) can be generated from these cells. In this study, ECs at 10 days post
      coitum (dpc) were tagged with Ac-LDL-DiI and were shown to release DiI+ HCs into
      the circulation after 12 h of whole embryo culture. The hematopoietic clusters in
      the main arteries were also stained with DiI. The circulating DiI+ HCs expressed
      c-Kit and half of these cells displayed blastic morphology. In vitro culture and
      in vivo reconstitution experiments demonstrated that the circulating DiI+ HCs
      contained definitive multipotent progenitors, including hematopoietic stem cells
      (HSCs). Furthermore, the sorted DiI+ HCs were able to colonize the fetal liver
      (FL) when introduced back into the blood stream of a secondary recipient embryo.
      These results suggest that Ac-LDL incorporating ECs can produce definitive HSCs
      and HCs colonizing FL in the mouse embryo.

PMID- 16433626
TI  - Origin and characterization of multipotential mesenchymal stem cells derived from
      adult human trabecular bone.
AB  - Much of the knowledge regarding the regulatory pathways for adult stem cell self
      renewal and differentiation has been obtained from the results of in vitro
      cultures. However, it is unclear if adult stem cells are controlled in the same
      way under physiological conditions. We examined this issue with respect to the
      migration of stem cells to tissue injury and how switch from a migratory state to
      one of proliferation wherein they participate in development. Building on our
      previous identification of multipotent stem cells in trabecular bone, we have
      examined the in vitro behavior of these cells within the bone milieu. We found
      that cell proliferation is inhibited within the trabecular bone niche as cells
      migrate out of the trabecular bone prior to proliferation. Additionally, multiple
      cell types were detected in adult trabecular bone, including osteoblasts,
      osteoclasts, endothelial cells, and Stro-1-positive mesenchymal stem cells.
      Furthermore, we demonstrated that Stro-1-positive cells migrated out of their
      native bone niche to generate multipotential stem and progenitor cells during in
      vitro culture. We conclude that self-renewal and differentiation of adult stem
      cells in connective tissues are tightly controlled and separately orchestrated
      processes. A regulatory network of extrinsic factors and intrinsic signals acts
      to stimulate the exit of stem cells from their niche so that they can localize to
      sites of wound healing, where they participate in development after functional
      differentiation.

PMID- 16433627
TI  - Transplantation of a novel cell line population of umbilical cord blood stem
      cells ameliorates neurological deficits associated with ischemic brain injury.
AB  - Umbilical cord blood (UCB) is a rich source of hematopoetic stem cells (HSCs). We
      have isolated a novel cell line population of stem cells from human UCB that
      exhibit properties of self-renewal, but do not have cell-surface markers that are
      typically found on HSCs. Analysis of transcripts revealed that these cells
      express transcription factors Oct-4, Rex-1, and Sox-2 that are typically
      expressed by stem cells. We refer to these novel cells as nonhematopoietic
      umbilical cord blood stem cells (nh-UCBSCs). Previous studies have shown that the
      intravenous infusion of UCBCs can ameliorate neurological deficits arising from
      ischemic brain injury. The identity of the cells that mediate this restorative
      effect, however, has yet to be determined. We postulate that nh-UCBSCs may be a
      source of the UCB cells that can mediate these effects. To test this hypothesis,
      we intravenously injected one million human nh-UCBSCs into rats 48 h after
      transient unilateral middle cerebral artery occlusion. Animals in other
      experimental groups received either saline injections or injections of RN33b
      neural stem cells. Animals were tested for neurological function before the
      infusion of nh-UCBSCs and at various time periods afterwards using a battery of
      behavioral tests. In limb placement tests, animals treated with nh-UCBSCs
      exhibited mean scores that were significantly better than animals treated with
      RN33b neural stem cells or saline. Similarly, in stepping tests, nh-UCBSC-treated
      animals again exhibited significantly better performance than the other
      experimental groups of animals. Analysis of infarct volume revealed that ischemic
      animals treated with nh-UCBSCs exhibited a 50% reduction in lesion volume in
      comparison to saline-treated controls. Histological analysis of brain tissue
      further revealed the presence of cells that stained for human nuclei. Some human
      nuclei-positive cells were also co-labeled for NeuN, indicating that the
      transplanted cells expressed markers of a neuronal phenotype. Cells expressing
      the human nuclei marker within the brain, however, were rather scant, suggesting
      that the restorative effects of nh-UCBSCs may be mediated by mechanisms other
      than cell replacement. To test this hypothesis, nh-UCBSCs were directly
      transplanted into the brain parenchyma after ischemic brain injury. Sprouting of
      nerve fibers from the nondamaged hemisphere into the ischemically damaged side of
      the brain was assessed by anterograde tracing using biotinylated dextran amine
      (BDA). Animals with nh-UCBSC transplants exhibited significantly greater
      densities of BDA-positive cells in the damaged side of the brain compared to
      animals with intraparenchymal saline injections. These results suggest that
      restorative effects observed with nh-UCBSC treatment following ischemic brain
      injury may be mediated by trophic actions that result in the reorganization of
      host nerve fiber connections within the injured brain.

PMID- 16433628
TI  - Immunomagnetic cell selection performed for HLA haploidentical transplants with
      the CliniMACS device: effect of additional platelet removal on CD34+ cell
      recovery.
AB  - Immunomagnetic CD34+ cell selection (ICS) is a widely employed technology in
      autotransplant and allotransplant settings. When an haploidentical transplant is
      performed, a high dose of purified CD34+ cells together with efficient T and B
      cell depletion are required to minimize the risks of graft versus host disease
      (GVHD) and Epstein-Barr virus (EBV)-related lymphoma. To ameliorate the
      performances of the CliniMACS (Miltenyi Biotec) ICS device, we compared 73 ICS
      performed following the manufacturer's recommended platelet depletion versus 48
      performed after adjunctive centrifugations to increase platelet depletion of the
      leukapheresis (LKF) product. A total of 121 ICS (from single or fractioned LKF
      products) were carried out on 93 LKF collected from 47 related healthy donors. A
      statistical significance in terms of CD34+ cell recovery (81.8% vs. 71.2%) was
      found in favor of the modified ICS procedure (p=0.0049) with a comparable stem
      cell purity and viability. The modification of the standard manufacturer's
      technique for increasing platelet depletion can further improve the recovery of
      stem cells with no influence on T and B cell depletion. These results demonstrate
      the negative influence exerted on CD34+ cell recovery by LKF platelet
      contamination.

PMID- 16433629
TI  - CD34+ stem cell recovery after positive selection of "overloaded" immunomagnetic
      columns.
AB  - Techniques for CD34+ cell enrichment of hematopoietic progenitor cells in grafts
      destined for transplantation of certain patients with the aim of lowering the
      amount of infused T lymphocytes and subsequently decreasing the risk of graft
      versus host disease (GVHD) have been well developed. Adaptations of these
      techniques should be useful for isolation of other phenotypically defined stem
      cells. However, a major limitation of techniques now available consists of the
      number of total nucleated cells or phenotypically defined stem cells that can be
      processed in a single procedure. Here, we show that recommended levels are much
      lower than the levels of cells that can be effectively processed by
      immunomagnetic sorting. Twenty-nine procedures were performed using the Clini-
      MACS (Miltenyi Biotec) device, which is recommended for processing <6x10(10
      )total nucleated cells or <6x10(8) CD34+ cells. Procedures were divided in groups
      according to their total cellular or CD34+ cell content. We achieved a median
      CD34+ cell recovery of 68.60% with a median purity of 98.56%, regardless of the
      loading dose when samples possessing 2-10x10(10) total nucleated cells and 0.8
      12.5x10(8) CD34+ cells were applied to a single column. The median levels of CD3+
      cells and CD19+ cells in the final product were depleted by 5 logs and 3.8 logs,
      respectively; no differences were noted when the initial loading dose was
      increased. Moreover, we found no correlation between the total number nucleated
      or CD34+ cells loaded and the resultant CD34+ cell recovery. In conclusion,
      levels of both total nucleated cells and CD34+ can be processed in a single
      procedure with satisfactory and similar CD34+ cell recovery when these columns
      are loaded with up to two times as many cells as recommended.

PMID- 16433631
TI  - Homocysteine- and cysteine-mediated growth defect is not associated with
      induction of oxidative stress response genes in yeast.
AB  - Intracellular thiols like cysteine, homocysteine and glutathione play a critical
      role in the regulation of important cellular processes. Alteration of
      intracellular thiol concentration results in many diseased states; for instance,
      elevated levels of homocysteine are considered to be an independent risk factor
      for cardiovascular disease. Yeast has proved to be an excellent model system for
      studying many human diseases since it carries homologues of nearly 40% of human
      disease genes and many fundamental pathways are highly conserved between the two
      organisms. In the present study, we demonstrate that cysteine and homocysteine,
      but not glutathione, inhibit yeast growth in a concentration-dependent manner.
      Using deletion strains (str2Delta and str4Delta) we show that cysteine and
      homocysteine independently inhibit yeast growth. Transcriptional profiling of
      yeast treated with cysteine and homocysteine revealed that genes coding for
      antioxidant enzymes like glutathione peroxidase, catalase and superoxide
      dismutase were down-regulated. Furthermore, transcriptional response to
      homocysteine did not show any similarity to the response to H2O2. We also failed
      to detect induction of reactive oxygen species in homocysteine- and cysteine
      treated cells, using fluorogenic probes. These results indicate that homocysteine
      and cysteine-induced growth defect is not due to the oxidative stress. However,
      we found an increase in the expression of KAR2 (karyogamy 2) gene, a well-known
      marker of ER (endoplasmic reticulum) stress and also observed HAC1 cleavage in
      homocysteine- and cysteinetreated cells, which indicates that homocysteine- and
      cysteine-mediated growth defect may probably be attributed to ER stress.
      Transcriptional profiling also revealed that genes involved in one-carbon
      metabolism, glycolysis and serine biosynthesis were up-regulated on exogenous
      addition of cysteine and homocysteine, suggesting that cells try to reduce the
      intracellular concentration of thiols by up-regulating the genes involved in
      their metabolism.

PMID- 16433633
TI  - Localization of GRP78 to mitochondria under the unfolded protein response.
AB  - The ubiquitously expressed molecular chaperone GRP78 (78 kDa glucose-regulated
      protein) generally localizes to the ER (endoplasmic reticulum). GRP78 is
      specifically induced in cells under the UPR (unfolded protein response), which
      can be elicited by treatments with calcium ionophore A23187 and
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor TG (thapsigargin). By
      using confocal microscopy, we have demonstrated that GRP78 was concentrated in
      the perinuclear region and co-localized with the ER marker proteins, calnexin and
      PDI (protein disulphide-isomerase), in cells under normal growth conditions.
      However, treatments with A23187 and TG led to diminish its ER targeting,
      resulting in redirection into a cytoplasmic vesicular pattern, and overlapping
      with the mitochondrial marker MitoTracker. Cellular fractionation and protease
      digestion of isolated mitochondria from ER-stressed cells suggested that a
      significant portion of GRP78 is localized to the mitochondria and is protease
      resistant. Localizations of GRP78 in ER and mitochondria were confirmed by using
      immunoelectron microscopy. In ER-stressed cells, GRP78 mainly localized within
      the mitochondria and decorated the mitochondrial membrane compartment.
      Submitochondrial fractionation studies indicated further that the mitochondria
      resided GRP78 is mainly located in the intermembrane space, inner membrane and
      matrix, but is not associated with the outer membrane. Furthermore, radioactive
      labelling followed by subcellular fractionation showed that a significant portion
      of the newly synthesized GRP78 is localized to the mitochondria in cells under
      UPR. Taken together, our results indicate that, at least under certain
      circumstances, the ER-resided chaperone GRP78 can be retargeted to mitochondria
      and thereby may be involved in correlating UPR signalling between these two
      organelles.

PMID- 16433635
TI  - Oral health for older people.

PMID- 16433632
TI  - Src-family kinases mediate an outside-in signal necessary for beta2 integrins to
      achieve full activation and sustain firm adhesion of polymorphonuclear leucocytes
      tethered on E-selectin.
AB  - In cell suspensions subjected to high-shear rotatory motion, human PMN
      (polymorphonuclear cells) adhered to E-selectin-expressing CHO (Chinese-hamster
      ovary) cells (CHO-E), and formed homotypic aggregates when challenged by E
      selectin-IgG fusion protein, by a mechanism that involved beta2 integrins. Both
      heterotypic and homotypic PMN adhesion was accompanied by tyrosine
      phosphorylation of a 110 kDa protein (P110). This event was prevented by blocking
      anti-(beta2 integrin) antibodies and by inhibitors of Src-family kinases,
      suggesting that it was part of an 'outside-in' signalling that was initiated by
      integrin engagement. Interestingly, Src-family kinase inhibitors prevented beta2
      integrin-mediated (i) homotypic PMN adhesion triggered by E-selectin-IgG, (ii)
      heterotypic CHO-E/PMN adhesion in mixed-cell suspensions, and (iii) firm adhesion
      of PMN to CHO-E monolayers under physiological flow. Similarly to PMN treated
      with Src-family kinase inhibitors, PMN from hck-/-fgr-/- and hck-/-fgr-/-lyn-/-
      mice showed significant impairment of beta2-integrin-mediated adhesion to CHO-E.
      Moreover, the expression of beta2 integrin activation epitopes at the sites of
      cell-cell contact in CHO-E/PMN conjugates was abolished by Src-family kinase
      inhibitors. One component of P110 was identified as the FAK (focal adhesion
      kinase) Pyk2 (proline-rich tyrosine kinase 2), which was phosphorylated in a
      beta2 integrin- and Src-family-kinase-dependent manner. Thus, Src-family kinases,
      and perhaps Pyk2, mediate a signal necessary for beta2 integrin function in PMN
      tethered by E-selectin.

PMID- 16433636
TI  - Oral health and morbidity--implications of oral infections on the elderly.
AB  - Detrimental effects of oral infections on general health have been known for
      almost 3000 years. Modern studies, however, have cast new light on the pathogenic
      mechanisms by which oral infections appear to link with morbidity and mortality.
      In particular, among the elderly, poor dental health seems to associate with all
      cause mortality. This review aims to provide an overview of present knowledge of
      these issues, starting from dental bacteraemia, oral mucosal infections and
      problems of drug resistance and, briefly, discussing what is known about the link
      between oral health and some systemic diseases such as atherosclerosis and type-2
      diabetes. The main conclusions are that scientific evidence is still weak on
      these interactions and that the elderly should be better taken into account when
      planning future studies. Functions of the body differ in the frail and diseased
      from those of the young. Consequently, novel prevention and treatment strategies
      should be developed and properly tested for combating oral infections in elderly
      populations. Specific suggestions for further research are outlined.

PMID- 16433637
TI  - In vitro biocompatibility of denture relining materials.
AB  - OBJECTIVE: The aim of the present study was to evaluate the in vitro
      biocompatibility of denture relining materials using cell culture tests and a
      test for irritation mechanisms. BACKGROUND: Denture relining materials contain
      non-reacted constituents that may leach out during use inducing local toxic or
      irritative effects. MATERIALS AND METHODS: One chemically cured, four visible
      light cured and five dual-cured products were included. Cured test specimens were
      used for the filter diffusion test, and extracts of cured specimens were applied
      in the MTT and the irritation test using the hen's egg test-chorioallantoic
      membrane (HET-CAM) method. RESULTS: Five of the tested materials were slightly or
      moderately cytotoxic in the filter diffusion test, and one product coated with a
      liner induced severe toxicity. Cell cultures incubated for 24 hour with the test
      samples were more damaged than those incubated for 2 hour. In the MTT test,
      extracts of nine of the 11 products induced cytotoxicity. No extracts showed
      irritation, whereas the coating and two bonding agents tested were strong
      irritants. CONCLUSION: Most of the tested materials contained water soluble,
      toxic substances that leach out of the products and that some time was needed to
      obtain cytotoxic amounts of the leachables. Many dental materials elicit
      cytotoxic response, but this does not necessarily reflect the long-term risk for
      adverse effects as the oral mucosa is generally more resistant to toxic
      substances than a cell culture.

PMID- 16433634
TI  - A proteomic approach reveals transient association of reticulocalbin-3, a novel
      member of the CREC family, with the precursor of subtilisin-like proprotein
      convertase, PACE4.
AB  - SPCs (subtilisin-like proprotein convertases) are a family of seven structurally
      related serine endoproteases that are involved in the proteolytic activation of
      proproteins. In an effort to examine the substrate protein for PACE4 (paired
      basic amino-acid-cleaving enzyme-4), an SPC, a potent protein inhibitor of PACE4,
      an alpha1-antitrypsin RVRR (Arg-Val-Arg-Arg) variant, was expressed in GH4C1
      cells. Ectopic expression of the RVRR variant caused accumulation of the 48 kDa
      protein in cells. Sequence analysis indicates that the 48 kDa protein is a
      putative Ca2+-binding protein, RCN-3 (reticulocalbin-3), which had previously
      been predicted by bioinformatic analysis of cDNA from the human hypothalamus. RCN
      3 is a member of the CREC (Cab45/reticulocalbin/ERC45/calumenin) family of
      multiple EF-hand Ca2+-binding proteins localized to the secretory pathway. The
      most interesting feature of the RCN-3 sequence is the presence of five Arg-Xaa
      Xaa-Arg motifs, which represents the target sequence of SPCs. Biosynthetic
      studies showed that RCN-3 is transiently associated with proPACE4, but not with
      mature PACE4. Inhibition of PACE4 maturation by a Ca2+ ionophore resulted in
      accumulation of the proPACE4-RCN-3 complex in cells. Furthermore, autoactivation
      and secretion of PACE4 was increased upon co-expression with RCN-3. Our findings
      suggest that selective and transient association of RCN-3 with the precursor of
      PACE4 plays an important role in the biosynthesis of PACE4.

PMID- 16433638
TI  - The effect of denture quality attributes on satisfaction and eating difficulties.
AB  - OBJECTIVES: The development of a measure, with complimentary normative and
      perceived needs, for the investigation of functional impairment of individual
      patients and the investigation of the physical causative bases of impairment.
      SUBJECTS: A consecutive sample of 119 complete denture (CD) wearers attending a
      Greek department of prosthetic dentistry took part in the study. All subjects
      presented with some complaint(s) of their dentures. METHOD: Functional assessment
      of dentures (FAD) criteria and structured questionnaires were used covering
      denture satisfaction (DS) and food difficulties with CDs. The questions used a
      five-point Likert scale. RESULTS: The results showed that there were
      statistically significant associations between satisfaction from dentures and
      eating specified foods. Statistically significant associations were also found
      between denture qualities and movement of upper dentures and difficulty eating
      specified foods, but not with an open question on the difficulty of eating
      unspecified foods. CONCLUSIONS: This study successfully validated a suitable
      model for the combined evaluation of denture quality with clear diagnostic
      criteria and closed questions on DS and perceived difficulties when eating
      specified foods. This could predict the need for treatment, monitor the impact of
      care and provide a feasible measure to meet the need of everyday clinical
      situations.

PMID- 16433639
TI  - Self-reported oral hygiene habits among institutionalised elderly and their
      relationship to the condition of oral tissues in Taubate, Brazil.
AB  - OBJECTIVES: To record self-reported hygiene habits, examine the oral conditions
      of a sample group of institutionalised elderly, and examine possible
      relationships between these habits and conditions. DESIGN: Cross-sectional.
      SETTING: All the institutions for the elderly in Taubate, Brazil. SUBJECTS: The
      entire population of these institutionalised elderly people (n = 553).
      INTERVENTION: The subjects were interviewed and underwent an oral examination.
      MAIN OUTCOME MEASURES: Oral hygiene habits, oral conditions and statistical
      relationships between habits and oral conditions were recorded. RESULTS: The
      average age of the subjects who knew their age (n = 364) was 74.9 years (+/
      12.9), and 64.7% of the sample group were females. Denture-related stomatitis was
      found in 19.5%, impaired manual dexterity in 40%, dry mouth sensation in 36.3%,
      difficulty in performing oral hygiene in 20%, no oral hygiene-related orientation
      in 54.1%, no periodic oral examinations in 59.5%, and no tongue cleaning in 68.3%
      was declared. Among dentate subjects, 73.3% had periodontal disease, 54.7% had
      caries, 26% reported no toothbrushing, and 7.3% reported flossing. Of the denture
      wearers, 7% did not brush their dentures. Denture-related stomatitis showed a
      statistical relationship with impaired manual dexterity (p = 0.012) and an
      inverse statistical relationship with denture brushing frequency (p = 0.006).
      Periodontal disease showed an inverse relationship to flossing (p < 0.001) and
      tongue cleaning (p = 0.0026). Caries showed an inverse relationship with tooth
      brushing (p = 0.043), flossing (0.022), proper oral hygiene orientation (p =
      0.041) and periodical check-ups (p = 0.007). CONCLUSION: Oral hygiene practices
      in this sample group were found to be inadequate, and statistically significant
      relationships were verified between the lack of good oral hygiene practices and
      the deleterious oral conditions.

PMID- 16433640
TI  - Comparison of antioxidant enzymes in saliva of elderly smokers and non-smokers.
AB  - OBJECTIVES: This study was designed to compare the levels of copper/zinc
      superoxide dismutase (Cu/Zn SOD), peroxidase (POx) and glutathione peroxidase
      (GSH-Px) in saliva of smokers and those in saliva of non-smokers. METHODS:
      Unstimulated saliva samples were collected from 88 elderly males (65 years old or
      over) who visited a private dental clinic. Forty-four subjects were current
      smokers (more than 20 cigarettes daily for at least 30 years) and 44 were non
      smokers. The levels of salivary thiocyanate, Cu/Zn SOD, GSH-Px, and POx activity
      were measured using standard procedures. RESULTS: The mean levels of salivary
      thiocyanate (SCN(-)) and SOD were significantly higher (p < 0.01) in the smoking
      group than in the non-smoking group, whereas the specific activity levels of POx
      and GSH-Px were significantly higher (p < 0.05) in the non-smoking group than in
      the smoking group. Significant correlation coefficients were found between the
      levels of SCN(-) and SOD (r = 0.37, p < 0.001). In the non-smoking group, a
      significant positive association was found between specific activity of POx and
      age (r = 0.33, p < 0.05). CONCLUSION: Measurement of SCN(-) and Cu/Zn SOD in
      human saliva might be useful for estimating the level of oxidative stress caused
      by cigarette smoke. Despite increased H2O2 level as a defense system induced by
      SOD, detoxification of H2O2 might be deteriorated in the oral cavity of elderly
      smokers.

PMID- 16433641
TI  - Efficacy of chlorhexidine-thymol varnish (Cervitec) against plaque accumulation
      and gingival inflammation in a geriatric population.
AB  - OBJECTIVES: To determine whether the 3-monthly application of chlorhexidine (CHX)
      thymol varnish is an effective method of controlling plaque and gingivitis in a
      group of institutionalised elderly as a complement to their usual oral hygiene
      practices. DESIGN: A 6-month double-blind clinical trial. SETTING: Two
      residential homes in Almeria (Spain). PARTICIPANTS: Fifty-six dentate subjects
      aged above 64 years who completed the 6-month study. INTERVENTION: The study
      subjects were randomly assigned to one of two groups (Cervitec or placebo).
      Varnishes were applied twice in the first week of the study and were applied
      again a month later and every 3 months until the end of the study. The patients
      continued with their usual oral hygiene practices throughout the study.
      MEASUREMENT: Plaque index and gingival index scores were determined at baseline
      and after 1, 3 and 6 months. RESULTS: Treatment with Cervitec varnish had a
      statistically significant effect overtime on the gingival index score (p =
      0.029), but not on the plaque index score (p = 0.651). The groups did not
      significantly differ in reductions in plaque or gingival index scores between
      baseline and 1, 3 or 6 months. CONCLUSION: According to these results, Cervitec,
      a CHX-thymol varnish, does not appear to reduce plaque and gingivitis by a 3
      monthly application in the institutionalised elderly with poor oral hygiene.
      Wider studies are required to investigate different varnishing protocols in
      geriatric populations.

PMID- 16433642
TI  - Oral lesions in elderly population: a biopsy survey using 2250 histopathological
      records.
AB  - OBJECTIVE: To perform an oral biopsy survey focused on the incidence of oral
      lesions in Brazilian elderly patients. METHODS: A total of 17 329 oral biopsy
      records were analysed and divided into two age groups: elderly patients, > or =60
      years old; and non-elderly patients, <60 years old. Information about sex, race,
      age and histopathological diagnosis (categorised in non-neoplastic and neoplastic
      lesions) was collected. Differences of diagnosis incidence were tested by
      comparison between two proportions (binomial test). RESULTS: The incidence of
      epithelial malignant neoplasms and pre-malignant lesions in the elderly group was
      higher than non-elderly group, as well as autoimmune diseases and salivary gland
      tumours. The three most prevalent lesions in the elderly group were inflammatory
      fibrous hyperplasia, squamous cell carcinoma, and fibroma. CONCLUSION: The
      distribution of oral diseases using biopsies allows greater accuracy in data
      about oral health of elderly patients, especially when considering malignant and
      pre-malignant lesions.

PMID- 16433643
TI  - Colonisation on the tongue surface by respiratory pathogens in residents of a
      nursing home--a pilot study.
AB  - OBJECTIVE: The morbidity and mortality of the dependent elderly that result from
      aspiration pneumonia have been recognised as a major geriatric health problem.
      The tongue has an extremely large surface area and due to its papillary structure
      can retain considerable quantities of food, and thus can support and harbour a
      large bacterial population. The purpose of this study was to gain more
      information on the microflora of the tongue surface and to assess the existence
      of oral infectious pathogens potentially causing respiratory disease in nursing
      home residents. SUBJECTS AND METHODS: The tongue bacterial flora of 69 nursing
      home residents were examined to identify microorganisms by the culture method.
      RESULTS: Thirteen species of microorganisms were detected from the tongue in this
      study. In 41 of 69 subjects (59%), potential respiratory pathogens, had colonised
      the tongue surface. CONCLUSION: The results of the present study revealed that
      bacteria that commonly cause respiratory infection colonised the tongue of
      nursing home residents, suggesting that it may function as a reservoir of
      potential respiratory pathogens to facilitate colonisation on the oropharynx.

PMID- 16433644
TI  - Cephalometric study of elderly with nearly intact dental arches.
AB  - OBJECTIVE: The purpose of this study was to investigate the craniofacial
      morphology of elderly people with many remaining teeth using cephalometric
      analysis. SUBJECTS AND METHODS: The subjects were 30 Japanese elderly who
      participated in the '8020 campaign 2001' in Bunkyo Ward, Tokyo, organised by The
      Dental Association of Tokyo, as well as 30 Japanese young adults with normal
      occlusion. Lateral cephalograms of all subjects were analysed using the Coben
      method. RESULTS: In the female elderly group, the lower face depth was smaller
      than in the younger adults. In the male elderly group, the height and depth of
      both the total face and the lower face were longer than in the younger group. In
      comparing the 8020 achievers with the younger group, the proportion of the lower
      facial height was greater than the upper facial height, and this finding was more
      pronounced in women than in men. CONCLUSION: For the lateral facial pattern of
      the elderly, a reduction of lower facial height because of tooth occlusal
      reduction was not apparent. It was clear that there are age differences for males
      and females; in addition, differences in the total face and lower face area of
      the elderly group were due to their having many remaining teeth over a long time
      period. Also, these changes were more apparent in women than in men, and it is
      clear that there is a male-female difference in ageing.

PMID- 16433645
TI  - An in vitro investigation of a comparison of bond strengths of composite to
      etched and air-abraded human enamel surfaces.
AB  - PURPOSE: The purposes of the study were to measure the tensile bond strength of
      composite resin to human enamel specimens that had been either etched or air
      abraded, and to compare the quality of the marginal seal, through the assessment
      of microleakage, of composite resin to human enamel specimens that had been
      either etched or air-abraded. MATERIALS AND METHODS: Thirty mandibular molar
      teeth were decoronated and sectioned mesio-distally to produce six groups, each
      containing ten specimens that were embedded in acrylic resin using a jig. In each
      of the four treatment groups, the specimen surfaces were treated by either
      abrasion with 27 or 50 microm alumina at 4 mm or 20 mm distance, and a composite
      resin was bonded to the treated surfaces in a standardized manner. In the two
      control groups the specimens were treated with 15 seconds exposure to 36%
      phosphoric acid gel and then similarly treated before being stored in sterile
      water for 1 week. All specimens were then subjected to tensile bond strength
      testing at either 1 or 5 mm/min crosshead speed. For the microleakage study, the
      degree of dye penetration was measured 32 times for each treatment group, using a
      neutral methylene blue dye at the interface between composite and either 27 or 50
      microm air-abraded tooth structure or etched enamel surfaces. RESULTS: The mean
      bond strength values recorded for Group 1 (phosphoric acid etch, 5 mm/min
      crosshead speed) was 25.4 MPa; Group 2 (phosphoric acid etch, 1 mm/min), 22.2
      MPa; Group 3 (27 microm alumina at 4 mm distance), 16.8 MPa; Group 4 (50 microm
      alumina at 4 mm distance), 16.9 MPa; Group 5 (27 microm alumina at 20 mm
      distance), 4.2 MPa; and for Group 6 (50 microm alumina at 20 mm distance) 3.4
      MPa. An analysis of variance (ANOVA) demonstrated significant differences among
      the groups, and a multiple comparison test (Tukey) demonstrated that
      conventionally etched specimens had a greater bond strength than air-abraded
      specimen groups. No significant difference in dye penetration could be
      demonstrated among the groups (p= 0.58). CONCLUSIONS: Composite resin applied to
      enamel surfaces prepared using an acid etch procedure exhibited higher bond
      strengths than those prepared with air abrasion technology. The abrasion particle
      size did not affect the bond strength produced, but the latter was adversely
      affected by the distance of the air abrasion nozzle from the enamel surface. The
      crosshead speed of the bond testing apparatus had no effect on the bond strengths
      recorded. The marginal seal of composite to prepared enamel was unaffected by the
      method of enamel preparation.

PMID- 16433646
TI  - Free radical damage in facsimile synovium: correlation with adhesion formation in
      osteoarthritic TMJs.
AB  - PURPOSE: The purpose of this study was to use the rat air pouch model of
      facsimile synovium to evaluate oxidative stress as a primary mechanism in the
      pathogenesis of degenerative temporomandibular joint (TMJ) disease. MATERIALS AND
      METHODS: Forty-nine Sprague-Dawley adult female rats were used to generate the
      standard rat air pouch model of facsimile synovium. This was accomplished by
      daily air injections (20 cc) subdermally through the dorsal skin. Hydrogen
      peroxide and ferrous iron (components of the Fenton reaction which generate free
      radicals) were introduced into the pouches of the 4-, 7-, and 14-day groups to
      generate oxidative stress. Control rats were injected with phosphate-buffered
      solution (PBS), pH 7.4. Either N-acetylcysteine (NAC), a powerful free radical
      scavenger, or ibuprofen were simultaneously injected with the Fenton reagents
      into the pouches of the 14-day treatment groups to modulate free radical-mediated
      protein damage to the synovium. Animals were euthanized at appropriate
      experimental intervals and biopsies obtained from specimens to analyze: (1)
      proteins' amino acid modification (carbonyl group formation), (2) protein
      hydrophobicity, (3) detection of low molecular weight protein degradation
      products, and (4) histological and gross anatomical observations. RESULTS: Free
      radicals introduced into the rat air pouch interacted with synovial tissues
      causing oxidation and breakdown of proteins. Clinical evidence of adhesion
      formation consistent with features found in osteoarthritis of the TMJ developed.
      The groups subjected to oxidative stress experienced statistically significant (p
      < 0.05) increases in carbonyl formation, carbonyls/protein, and low molecular
      weight protein fragments. These groups also showed significant (p < 0.05)
      hydrophobicity changes consistent with free radical attack. Control synovial
      tissues were statistically undamaged. The 14-day NAC and ibuprofen treatment
      groups experienced statistically significant (p < 0.05) decreases in total
      carbonyl formation, carbonyls/protein, and hydrophobicity. Histological and gross
      observations in free radical damaged synovium exhibited features consistent with
      known arthoscopic and arthrocentesis findings in diseased TMJs. CONCLUSIONS: This
      study suggests that the rat air pouch model of facsimile synovium develops
      clinical evidence of adhesions and biochemical signs of protein modification when
      subjected to free radical attack. NAC and ibuprofen prevented carbonyl formation
      as well as hydrophobicity changes indicative of oxidative stress damage in
      facsimile synovium. These findings are consistent with features of degenerative
      human TMJ disease. Future direction may be taken from this study to postulate new
      analysis techniques and treatment modalities for patients with degenerative TMJ
      disease.

PMID- 16433647
TI  - In vivo stress behavior in cemented and screw-retained five-unit implant FPDs.
AB  - PURPOSE: When fixing implant-supported fixed partial dentures (FPDs), it is
      important to achieve passive fit. The objective of the in vivo study presented
      was to quantify the strain development during the fixation of screw- and cement
      retained FPDs. MATERIALS AND METHODS: After informed patient consent had been
      obtained (Ethics commission Approval No. 2315; FAU Erlangen-Nuremberg, Germany),
      four groups of five-unit FPDs (five samples per group) were fabricated and
      investigated in vivo. Group 1: Cementable, repositioning technique impression,
      burn out plastic coping; Group 2: Screwable, pickup technique impression, burn
      out plastic coping; Group 3: Screwable, pickup technique impression, cast to gold
      cylinder; Group 4: Screwable, pickup technique impression, bonded to gold
      cylinder. Two strain gauges (SG) were attached to the pontics of each bridge (SG
      M and SG-D) to measure the strains that occurred during either the cementing or
      screw-in process. The final values were recorded for analysis. RESULTS: The mean
      strain values (microm/m) for each SG were: Group 1: SG-M 32 microm/m, SG-D: 89
      microm/m; Group 2: SG-M 302 microm/m, SG-D: 197 microm/m; Group 3: SG-M 458
      microm/m, SG-D: 268 microm/m; Group 4: SG-M 269 microm/m, SG-D: 52 microm/m.
      CONCLUSIONS: Although the bridges were clinically acceptable, none of them
      revealed a truly passive fit with zero microstrain. In contrast to conventional
      screw-retained bridges, cement retention seems to result in lower strain levels.
      Bonding bridge pontics to prefabricated implant components seems to allow both
      the retrievability of a screw-retained bridge and produce moderate strain values.

PMID- 16433649
TI  - An alveolar bone augmentation technique to improve esthetics in anterior ceramic
      FPDs: a clinical report.
AB  - This clinical report describes guided bone augmentation for treatment of a facial
      maxillary alveolar bone defect to enhance the esthetic result for an all-ceramic
      fixed partial denture (FPD). A combination of decalcified freeze dried bone
      allograft and resorbable human pericardium, in conjunction with cortical channel
      expansion, was used for the augmentation process to eliminate a secondary
      surgical procedure. Post-operative examinations showed improvement in the
      alveolar bone contour. The regeneration of the missing osseous structure was
      accomplished to support the future esthetic soft tissue contours. This osseous
      regenerative technique significantly increased the functional and esthetic
      outcome of the final FPD by restoring the alveolar ridge defect to its original
      dimension.

PMID- 16433648
TI  - Factors associated with masticatory performance in unilateral distal extension
      removable partial denture patients.
AB  - PURPOSE: Masticatory performance of denture patients is an outcome of the
      intricate inter-relationship between patient characteristics and denture
      construction. This study aimed to identify both patient- and denture-related
      factors associated with masticatory performance in unilateral distal extension
      removable partial denture patients (RPDs). MATERIALS AND METHODS: Seventy-two
      patients (25 male and 47 female, mean age 63.4 +/- 6.7 years) with unilateral
      distal extension RPDs were included in the study. The Mixing Ability Index (MAI)
      obtained from a chewing test using standard two-colored wax cubes, determined
      masticatory performance. The effect of each evaluated factor on masticatory
      performance was first determined by an independent t-test or one-way analysis of
      variance. The statistically significant factors were entered in a model of
      multivariate linear regression analysis to estimate the independent effect on
      MAI. RESULTS: The MAI ranged from -3.06 to 0.80 (Mean -0.71 +/- 0.86). Univariate
      analyses identified male gender, high maximum bite force, more functional tooth
      units, and natural dentition opposing RPDs as patient factors increasing the MAI.
      Multivariate analysis (adjusted R(2)= 0.346) revealed that gender (p < 0.001),
      maximum bite force (p= 0.02), and number of functional tooth units (p= 0.03) were
      independent predictors for masticatory performance. None of the denture-related
      factors had a significant influence on MAI. CONCLUSION: Gender, maximum bite
      force, and number of functional tooth units were the main factors influencing
      masticatory performance of unilateral distal extension RPD patients.

PMID- 16433650
TI  - Prosthodontics as a specialty private practice: net income of private
      practitioners.
AB  - PURPOSE: The aim of this study was to use data from a survey of prosthodontists
      in the US to examine average net earnings of prosthodontists in private practice.
      MATERIALS AND METHODS: A survey of 2500 prosthodontists in the US was used to
      estimate the net earnings of practicing prosthodontists. The national average net
      earnings of prosthodontists in private practice was estimated along with average
      earnings for subgroups of prosthodontists. Estimates for private practitioners by
      age, gender, size of practice, full-time/part-time status, practice ownership,
      and by type of treatment procedures rendered by the practitioner were also
      included. RESULTS: Average earnings for prosthodontists in private practice on a
      primary or secondary basis were estimated to be $215,300 and for prosthodontists
      who own or share in the ownership of a private practice, $233,920. Reported
      earnings estimates ranged from $96,160 for non-owners of a private practice and
      $103,350 for part-time private practitioners to $233,920 for practice owners and
      $275,170 for prosthodontists in practice with two prosthodontists. The average
      earnings of prosthodontists who are practice owners were estimated to be 35%
      higher than the corresponding general practitioners. CONCLUSION: Average net
      earnings are often used to examine the current economic health of a profession.
      The average net earnings of prosthodontists in private practice exceed the
      average net income reported by the American Dental Association for all dentists
      and all general practitioners and they are competitive with earnings among all
      specialty groups. This evaluation of the net earnings of prosthodontists shows
      that prosthodontics offers a competitive career opportunity for the general
      dentist with a personal desire to pursue advanced dental education in a specialty
      as a profession.

PMID- 16433651
TI  - A practical method for chairside repair of debonded porcelain denture teeth.
AB  - The bonding of porcelain denture teeth to polymethylmethacrylate remains a
      clinical problem. In this article an alternative chairside method, based on
      silica coating and silanization for adhesion of denture tooth porcelain to
      polymethylmethacrylate is described.

PMID- 16433652
TI  - Use of stereolithographic templates for surgical and prosthodontic implant
      planning and placement. Part I. The concept.
AB  - Surgical and prosthodontic implant complications are often an inadvertent
      sequelae of improper diagnosis, planning, and placement. These complications pose
      a significant challenge in implant dentistry. Presented in this article is a
      technique using a highly advanced software program along with a rapid prototyping
      technology called stereolithography. It permits graphic and complex 3D implant
      simulation and the fabrication of computer-generated surgical templates. These
      templates seat directly on the bone and are preprogrammed with the individual
      depth, angulation, and mesio-distal and bucco-lingual positioning of individual
      implants as planned during the 3D computer simulation.

PMID- 16433653
TI  - Simplified fabrication of surgical template for orthodontic-implant treatment.
AB  - This article proposes a simple method to fabricate an implant surgical template
      that provides good visual access, operator flexibility, and template stability
      for use in multidisciplinary cases involving orthodontic devices.

PMID- 16433654
TI  - Removable partial denture education in U.S. dental schools.
AB  - PURPOSE: A survey of U.S. dental schools was conducted in 2001 to determine the
      curricular structure, techniques, and materials used in predoctoral clinical
      removable partial denture (RPD) programs. MATERIALS AND METHODS: The
      questionnaire was mailed to the chairperson of the prosthodontic/restorative
      departments of 54 U.S. dental schools. Of these, 44 schools returned the
      completed survey, resulting in a response rate of 82%. RESULTS: Results from this
      survey show that a large majority of schools are using similar materials in
      clinical RPDs; for instance, using modeling compound for border molding final
      impression trays (61%) and using a semi-adjustable articulator for mounting
      preliminary casts (90%) and final casts (98%). In addition, a large majority of
      schools are using similar techniques in clinical RPDs, such as border molding the
      edentulous areas of the final impression tray (80%) and using the altered cast
      impression technique (59%). A set post-insertion protocol is present for patients
      who receive partial dentures in the majority of the schools (93%). Only 25% of
      schools reported incorporating new educational materials such as the use of
      Portrait artificial teeth at the predoctoral level. Eighteen percent of schools
      are allowing students to graduate without a set number of RPD clinical
      requirements as has been traditionally the case. CONCLUSIONS: Predoctoral
      clinical RPD programs vary from school to school, yet a large percentage of
      schools agree on many topics.

PMID- 16433657
TI  - Neuropsychological assessment with the Visual Gestalt Test: psychometric
      properties and differential diagnostic probabilities.
AB  - The Visual Gestalt Test is a neuropsychological instrument developed for
      evaluation of learning and memory of visuo-spatial material. A revised strategy
      of scoring has motivated the present study, where data from 153 normal persons,
      99 epilepsy patients, and 24 depressed patients are presented and compared. The
      Visual Gestalt Test is observed to discriminate between normal and diagnosed
      groups in several ways. Additionally it is found to discriminate between
      depressed and brain damage subgroups of patients. Data are presented in order to
      supplement previously published ways of scoring and norms. Practical guidelines
      for the clinical applications of the test are suggested as perspectives.

PMID- 16433658
TI  - The relationship between the quality of cooperative learning, students' goal
      preferences, and perceptions of contextual factors in the classroom.
AB  - This study examined relationships between the quality of cooperative learning
      (CL) and students' goal preferences and perceptions of contextual factors in the
      classroom. Subjects were 1,920 students in secondary vocational schools. The
      study focused on four different types of goals: social support, belongingness,
      mastery, and superiority goals. It was found that social support goals had the
      strongest relation with the quality of CL. Further we found that the quality of
      CL was best predicted by a combination of social support goals, evaluations of
      the extent that students were taught cooperation skills, perception of teacher
      monitoring behavior, and the availability of academic and emotional peer support.
      Female students' preferences for mastery and social goals were stronger than
      those of male students, whereas male students had a stronger preference for
      superiority goals. Program type functioned as a moderator variable within the
      relation of students' superiority/ individuality goals and the quality of CL.

PMID- 16433659
TI  - Comparison of several shortened versions of the EMBU: exploratory and
      confirmatory factor analyses.
AB  - The aim of the present study was to analyze the psychometric properties of
      different versions of the EMBU (Egna Minnen av Barndoms Uppfostran - My memories
      of upbringing) in a non-clinical sample of adolescents. The factor structure of
      the questionnaire was studied by means of more adequate exploratory and
      confirmatory factor procedures in order to ascertain which version achieves a
      better fit to data. The 64-item version of the EMBU was administered to a non
      clinical sample of 832 adolescents. Exploratory and Confirmatory factor analyses
      were carried out for successive versions of 64, 37, 24 and 23 items. The
      theoretical four-factor structure of the 64-item version is not replicated in a
      factor analysis through principal axis extraction with direct oblimin rotation.
      The "Favoring Subject" factor was not found. 37 items present loadings equal to
      or larger than 0.30 for the "Rejection", "Emotional Warmth" and "Overprotection"
      factors. A re-analysis of these items shows a clear three-factor structure. When
      Arrindell et al.'s (1999) 23-item version was analysed, the three expected
      factors were also found. Confirmatory factor analyses allow us to reduce the 36
      item version to a shorter one of 24 items. This last version achieves the best
      fit to data, including the 23-item version. The new 24-item version improves the
      construct validity of the EMBU and presents similar reliability coefficients.

PMID- 16433660
TI  - The relationship between viewing US-produced television programs and intentions
      to drink alcohol among a group of Norwegian adolescents.
AB  - The aim of this study was to examine the influence of exposure to US-produced
      television programs and family rules prohibiting alcohol use on the development
      of normative beliefs, expectancies, and intentions to drink alcohol in the next
      12 months among a group of Norwegian adolescents who reported that they had not
      previously consumed alcohol. Data were collected via a survey administered to 622
      eighth and ninth graders enrolled at ten junior highs in southeastern Norway. To
      examine these relationships we tested the fit of a structural equation model
      which was based on the Theory of Planned Behavior (Ajzen, 1988). Data from the
      non-drinkers (n= 392, 63% of the respondents) were used. To control for the
      influence of peer drinking on behavioral intentions, our model was tested under
      two group conditions: (1) those subjects reporting that they have no friends who
      drink alcohol and (2) those subjects reporting that they have one or more friends
      who drink. The findings indicate that the influence of TV exposure was a
      significant predictor (directly) of normative beliefs, expectancies (indirectly)
      and intentions to drink (both directly and indirectly) only for those subjects
      who reported having no friends who drink. For the group with non-drinking
      friends, family rules constrain intentions only indirectly by influencing
      normative beliefs. For those with friends who drink, however, family rules have a
      direct (inverse) effect on intentions. It is concluded that exposure to US
      produced television programs functions as a limited knowledge source only for
      those subjects who had little or no personal experience with alcohol while the
      presence of family rules have limited impact on behavioral intentions.

PMID- 16433661
TI  - Episodic chasing in pathological gamblers using the Iowa gambling task.
AB  - "Chasing ones losses" is a key symptom among pathological gamblers (PGs). This
      study focuses on quantitative differences in episodic chasing (i.e., sequences of
      disadvantageous decisions within a single gambling session) between PGs and non
      pathological gamblers (NPGs). We compared 61 PGs and 39 NPGs on the Iowa Gambling
      Task (IGT) and the Zuckerman Sensation Seeking Scale (SSS). The PGs showed
      significantly more chasing and had significantly poorer decision-making
      strategies than NPGs, particularly among males (F = 4.52, p < 0.05). Random
      players were significantly less sensation seeking than advantageous and
      disadvantageous (i.e., chasing) players, but there was no interaction with group
      or gender. The results suggest that quantifiable within-session gambling behavior
      holds important implications for detecting underlying vulnerabilities to gambling
      pathology.

PMID- 16433662
TI  - Stimulus affectivity of the Danish Word Association Test as measured by response
      heterogeneity and Rasch scaled number of prolonged reaction times.
AB  - With the purpose of increasing the knowledge of the psychometric properties of
      the 70-item Danish Word Association Test, data from three samples of non-patients
      and psychiatric patients (N = 326) were used to provide two measures of
      affectivity of the stimulus words, response heterogeneity and reaction time
      prolongation. It was possible to fit an item response theory one-parameter
      measurement (Rasch) model to the number of reaction time prolongations (> or =3
      seconds) for 54 of the stimulus words. Correlation between Rasch-model item
      parameters and response heterogeneity was high (r = 0.86), while no correlation
      was found between either of these measures and frequency of the stimulus words in
      the Danish language. Both measures of stimulus affectivity supported a
      theoretically based classification of stimulus words as emotional or neutral.
      Response heterogeneity measures and Rasch measurement item and person parameters
      for reaction time prolongations are provided.

PMID- 16433663
TI  - Children of divorce in a Scandinavian welfare state: are they less affected than
      US children?
AB  - A fairly common view holds that children's risks of negative outcomes associated
      with family dissolution are generally small or even nonexistent in Scandinavia,
      and clearly smaller than what is usually found in the United States. This view
      was empirically examined in a recent large-scale study of 4,127 12-15-year-old
      children in Norway, of whom 623 had experienced parental divorce and lived in a
      single-mother family. The somewhat paradoxical pattern of findings was as
      follows: (a) The negative associations between parental divorce and various
      outcomes were found to be generally very similar in Norway and the United States
      in spite of the great differences in family policy and welfare benefits for
      single mothers (at the macro level); and (b) Mediational effects of family
      economic resources were in both countries most marked for the academic
      achievement area, and the predictive power of such variables was quite similar,
      again in spite of the great differences in absolute level of the economic
      resources available to single-mother families in the two countries. The results
      cast some doubt on the value of the absolute economic deprivation perspective in
      explaining the results, and the many Norwegian welfare benefits do not seem to
      mitigate the association between divorce and negative outcomes for the children
      involved. Also policy implications derived from the economic deprivation
      perspective are questioned. Alternative interpretations of the findings involving
      relative deprivation and economic resources as a partial proxy for other non
      economic factors are briefly discussed.

PMID- 16433664
TI  - Adolescent adjustment and well-being: effects of parental divorce and distress.
AB  - This study investigates the long-term effects of parental divorce on adolescent
      psychological adjustment and well-being, and to what extent the effects are
      accounted for by parental psychological distress. Data were collected among 8,984
      Norwegian adolescents (13-19 years) and their parents. Outcome variables were
      symptoms of anxiety and depression, subjective well-being, and three areas of
      school problems. Parental divorce was found to be associated with both higher
      mean levels and larger variances in adolescent problems. Divorce and parental
      distress contributed independently to adolescent distress, supporting the notion
      of "double exposure" effects. The prevalence of adolescents with substantial
      distress symptoms was 14% among those with non-distressed non-divorced parents
      and 30% among those with divorced and distressed parents. In general effects
      remained when controlling for demographic factors. Long-term effects of divorce
      on symptoms of anxiety and depression were stronger among girls than among boys.

PMID- 16433665
TI  - Histology, immunohistochemistry and ultrastructure of the tonsil of the soft
      palate of the horse.
AB  - The tonsil of the soft palate was an oval, flat structure located centro
      rostrally on the oral surface of the soft palate. Its stratified squamous non
      keratinized epithelium was perforated by holes or small crypts the deeper parts
      of which were loosely spongiform inter-digitated with lymphoid tissue. These
      unusual features have not previously been reported in tonsils of any species.
      Crypts and reticulated epithelium as found in the lingual and palatine tonsils
      were not observed. Lectins showed varying affinities for specific layers of the
      epithelium. M cells were not observed. A few Langerhans cells were distributed
      among surface epithelial cells. Lymphoid tissue was arranged loosely and in
      isolated lymphoid follicles in the subepithelial lamina propria mucosae. Although
      IgA+ cells and macrophages were proportionately more numerous the amount of
      lymphoid tissue was much less than in the lingual and palatine tonsils. Most of
      the follicular germinal centres lacked a darkly stained corona. CD4 positive were
      more numerous than CD8+ lymphocytes and were distributed in the parafollicular
      and inter-follicular areas. Large clusters of mucus acini positive for glycogen,
      acidic and neutral mucopolysaccharides separated lymphoid tissue from deeply
      placed striated muscle. Only a few high endothelial venules were observed in the
      parafollicular and inter-follicular areas. These had relatively few vesiculo
      vacuolar or other organelles in their high endothelial cells and few lymphocytes
      attaching to their walls.

PMID- 16433666
TI  - On the weight-bearing function of the medial coronoid process in dogs.
AB  - The shape of and proportions between the surface areas of the medial coronoid
      process (MCP) and the fovea of the radial head were determined in 88 juvenile
      dogs and 146 adult dogs grouped as giant, large, mid-sized, chondrodystrophic, or
      small dogs. Thereby, the longitudinal (length) and transverse (width) extension
      of the MCP and fovea of the radial head have been measured. Original values were
      used to describe changes of the parameters attributed to growth. Normalized
      values (i.e. values expected in case of a width of the fovea of the radial head
      of 20 mm) were used to determine potential differences between constitutional
      types. All original values increased during growth (P < 0.05) except for the
      width and length of the MCP in chondrodystrophic and small breeds. Normalized
      values revealed a proportional decrease in width and length of the MCP during
      growth (P < 0.05) compared with the radial head. In adults, the normalized MCP
      was widest in giant dogs followed by large, mid-sized, small, and
      chondrodystrophic breeds. The MCP was also longest in giant dogs but shortest in
      large and chondrodystrophic dogs with those of large dogs being significantly (P
      < 0.05) shorter than those in giant, mid-sized and small dogs. Present results
      suggest that a deficiency in length-growth of the MCP--which has been present
      especially in large dogs--results in smaller humeral contact areas and decreased
      weight-bearing capacity of the MCP. Because loading forces acting on the MCP
      increase with body weight, the condition noted in large dogs might increase the
      risk of fragmentation of the MCP in these.

PMID- 16433667
TI  - Morphoquantitative aspects of NADH-diaphorase myenteric neurons in the ileum of
      diabetic rats treated with acetyl-L-carnitine.
AB  - In this work, we investigated the effect of the acetyl-L-carnitine (ALC)
      supplementation (200 mg/kg/day) on the myenteric neurons of the ileum of rats
      made diabetic by streptozotocin (35 mg/kg, i.v.). Four groups were used: diabetic
      (D), diabetic supplemented with ALC (DC), control (C) and control supplemented
      with ALC (CC). After 15 weeks of diabetes induction the animals were killed and
      the ileum was collected and subjected to whole-mount preparation to evidence the
      myenteric neurons through the histochemical technique of the NADH-diaphorase. The
      density of neurons seen in 12.72 mm2 of ileum showed no difference among the
      groups, although in group D it was 22% smaller than in group C, while group DC
      was 9% smaller to group CC. The profiles of the cell bodies (PC) of 1000 neurons
      per group were analysed. The neurons PC in group D decreased (P < 0.0001) when
      compared with other groups and increased (P < 0.0001) when compared with group
      DC. The incidence of neurons with a PC inferior to 200 microm2 was larger in
      group D. The frequency of neurons with a PC higher than 200 microm2 in group DC
      was close to those seen in groups C and CC. We concluded that ALC eases the loss
      of neurons and makes the incidence of myenteric neurons with a PC higher than 200
      microm2 similar to the control rats.

PMID- 16433668
TI  - Computed tomographic anatomy of the canine temporal bone.
AB  - This study aims to identify and describe structures of the temporal bone in
      normal dogs that can be depicted using computed tomography (CT). Five normal dogs
      of different breeds and both sexes ranging from 0.5 to 8 years were used as the
      study material. CT images of 2 mm thickness without abnormalities in the temporal
      bone were reviewed and analysed in bone and soft tissue settings. All images were
      compared with corresponding E 12 plastic-embedded cross sections of 3 mm
      thickness, which were acquired from anatomic cross sections of frozen beagles.
      The sections were provided from the Department of Pathobiology (Institute of
      Anatomy). CT is able to image all relevant bony structures within the temporal
      bone. Concerning soft tissue structures, CT allows their localization by using
      bony markers, i.e. the internal acustic meatus for the cranial nerves VII and
      VIII or the canals for the internal carotid artery and the temporal sinus. The
      provided reference images are meant to improve orientation within the complex
      anatomy of the temporal bone. On condition that slice thickness is equal to or
      smaller than 2 mm and bony setting is supplied, CT is able to visualize all
      relevant structures within the temporal bone. However, in clinical settings the
      combined look on air, liquids and bone as well as the contrast enhancement of
      soft tissues might prefer magnetic resonance imaging to CT.

PMID- 16433669
TI  - Serotonin-containing cells in the gastrointestinal tract of newborn foals and
      adult horses.
AB  - Serotonin (5-hydroxytryptamine, 5-HT), a regulatory amine of mucosal
      enterochromaffin cells plays an important role in the control of gastrointestinal
      smooth muscle contraction and epithelial secretion. Serotonin has also been
      associated with gastric ulcers, diarrhoea and abdominal pain. In spite of the
      high incidence of these gastrointestinal disorders in newborn foals and adult
      horses, no data are available regarding 5-HT immunoreactive cells (i.c.) in the
      gastrointestinal tract (GIT) of foals, and for adult horses, data are incomplete
      and contradictory. In this study, the distribution and relative frequency of 5-HT
      i.c. in the GIT of newborn foals and adult horses were determined
      immunohistochemically. In foals as in adults, a relatively large number of 5-HT
      i.c. were detected in all portions of the GIT. In foals, a significantly higher
      amount of cells was found in the pyloric region and margo plicatus of the
      stomach, as well as in the caecum and colon ascendens compared with adults. Our
      results provided rationale for further research concerning the role of 5-HT i.c.
      during the milk diet or in the regulation of gastrointestinal growth/cell
      proliferation, and in the pathogenesis of gastric ulcers, especially in newborn
      foals.

PMID- 16433670
TI  - Scanning electron microscopic study of the functional anatomy of the porcine
      oviductal mucosa.
AB  - A three-dimensional model has not been clearly established for the porcine
      oviductal mucosa. The oviducts of 12 cyclic sows were examined by Scanning
      Electron Microscopy to study the structure and nature of the mucosal arrangement
      of the oviduct. Epithelial cyclic changes were also studied. The oviductal
      infundibulum is an asymmetric funnel-shaped structure surrounding the ostium, in
      which a wide and a narrow side can be distinguished. The mucosa is more complex
      in the narrow side, showing numerous and tortuous longitudinal primary folds,
      while the mucosa becomes simpler in the wide side. Around the ostium abdominale
      wide secondary folds form cul-de-sacs, with their opening pointing in ovarian
      direction. Areas between folds throughout the lumen of the oviduct show a high
      degree of complexity. Inter-fold spaces are occupied by a system of irregular
      grooves and pockets, with the presence of basal crypts in the caudal oviduct.
      Marked variations were observed in the oviductal epithelium depending on the
      oviductal segment, basal or apical areas of the folds, and phase of the oestrous
      cycle. Cyclical changes were observed in the infundibulum and ampulla, so that
      prominent and numerous ciliated cells lined apical areas of the folds in the
      follicular phase; whereas secretary cells were predominant throughout all areas
      of epithelial surface in the luteal phase. The oestrous cycle phase appeared do
      not affect the epithelial population cells of the caudal segments of the oviduct:
      ciliated and secretory cells uniformly lined apical and basal areas of the folds.
      The topography of the oviduct provides a complex system of regulation, which may
      influence not only the passage of cells, but also movement of fluid within the
      oviductal canal.

PMID- 16433671
TI  - Microscopic anatomy of the ringed seal (Phoca hispida) lower respiratory tract.
AB  - The microscopic anatomy of the ringed seal lung exhibits unique features and many
      features similar to those described in other seal species. Unique features
      include: Trachealis muscle predominately oriented longitudinally; Large veins
      within the tracheal wall supported by elastic fibers; Goblet cells and
      pseudostratified epithelium lining the duct system of bronchial glands of the
      segmental bronchi; Lamina propria of the segmental bronchus heavily invested with
      elastic fibers clustered into dense longitudinal bundles; and Capillaries and
      venules covered with squamous epithelium protruding into bronchiolar lumina.
      Common features include: Cartilage support of the bronchial tree extending
      distally into respiratory bronchioles; Smooth muscle enhancements in the distal
      airways producing sphincter like formations; and Lungs extensively supported with
      interstitial tissue, which divide lungs into lobules.

PMID- 16433672
TI  - Histology and histochemistry of the pharyngeal cavity and oesophagus of the
      silverside Odontesthes bonariensis (Cuvier and Valenciennes).
AB  - The histology of the pharyngeal cavity and oesophagus of the freshwater
      'silverside'Odontesthes bonariensis (Cuvier and Valenciennes) and the
      characteristics of their mucous cells were investigated. The histological
      characterization of its digestive wall revealed that the mucosa is thrown with
      longitudinal folds. The epithelium covering the folds was stratified with
      abundant mucous cells and gustative corpuscles, which are lacking in the
      oesophagus. The muscularis mucosa was absent. The submucosa presented the
      compactum stratum. The muscularis was organized in longitudinal and circular
      layers of muscular striated fibres. The serosa with a flat epithelium was located
      only in the oesophagus. Using histochemical procedures including methods for
      localization and characterization of glycoproteins (GPs), no differences were
      detected between the mucous cells contents of the pharyngeal cavity and those of
      the oesophagus. The mucous cells showed a weak periodic acid-Schiff (PAS)
      positive reaction in their content. The reactions for the differential analysis
      of sialic acids from GPs are feeble for periodic acid-Schiff at low temperature
      and low pH (PA*S) and KOH/PA*S and strong for periodic acid/borohydride/KOH/PAS
      (PA/Bh/KOH/PAS) and KOH/PA*/Bh/PAS revealing the scarce presence of C7 or C9
      substituted and non-substituted sialic acids and the abundance of C7, C8
      substituted sialic acids, O-acyl sugars and neutral sugars respectively. The
      results suggest that the pharyngeal cavity with the gustative corpuscles would
      induce the gastric secretion whereas the oesophagus is mainly involved in the
      transport of the food bolus to the stomach with the aid of abundant secretion of
      mucus. GPs secreted on the surface of the mucous cells, likely related to
      environmental conditions, would be involved in the lubrication, protection
      against abrasion and inhibition of microorganism proliferation.

PMID- 16433673
TI  - The gross anatomy of the male reproductive system of a neotropical rodent: the
      agouti (Dasyprota leporina).
AB  - The literature available on the agouti (Dasyprocta leporina) is very limited. The
      agouti is a Neotropical rodent found in Trinidad and Tobago, Central and South
      America. This study focuses on one of the many unexplored areas relating to the
      species, the male reproductive system. The results showed that the mean
      testicular length, diameter and weight was 3.67 +/- 0.12 cm, 1.67 +/- 0.04 cm and
      5.03 +/- 0.52 g respectively. The paired testes and epididymis were found in
      contact with the abdominal muscles within scrotal pouches, which are evaginations
      of the caudoventral abdominal wall. The caput epididymis is enclosed by a fat
      body. The ductus deferens has a mean length and diameter of 10.98 +/- 0.40 cm and
      0.14 +/- 0.01 cm respectively. At the urethral end of the ductus deferens the
      diameter of each duct expends to form the ampulla. The mean diameter of each of
      the ampulla was 0.25 cm. The accessory sex organs of the male agouti (D.
      leporina) include the vesicular glands, the coagulating glands, the prostate
      glands and the bulbourethral glands. The penis of the agouti is U-shaped with a
      mean length of 9.90 +/- 0.43 cm. The glans penis contains an os penis, a pair of
      lateral penile cartilages and paired ventral keratinaceous styles.

PMID- 16433674
TI  - Comparative macroanatomical study of the neurocranium in some carnivora.
AB  - This study was carried out to investigate the specific anatomical features of the
      neurocranium of the skull of the dog, cat, badger, marten and otter. Twenty-five
      animals (five from each species) were used without sexual distinction. The
      neurocranium consists of os occipitale, os sphenoidale, os pterygoideum, os
      ethmoidale, vomer, os temporale, os parietale and os frontale. The processus
      paracondylaris is projected ventrally in the cat, dog, marten and badger, and
      caudally in the otter. Two foramina were found laterally on each side of the
      protuberantia occipitalis externa in the otter, and one foramen was found near
      the protuberantia occipitalis externa in the badger. Foramen was not seen in
      other species. Paired ossa parietalia joined each other at the midline, forming
      the sutura sagittalis in the badger, dog, otter and cat while it was separated by
      the linea temporalis in the marten. The os frontale was small in otters, narrow
      and long in martens, and quite wide in cats and dogs. The bulla tympanica was
      rounded in the marten, dog, cat and badger, dorsoventral compressed in otter, and
      it was very large in all species examined. These observations represented
      interspecies differences in the neurocranium of marten, otter, badger, cat and
      dog.

PMID- 16433675
TI  - Mixed mesodermal and mesenchymal origin of myotomal muscles in pike (Esox lucius:
      Teleostei).
AB  - During the myotomal myogenesis in pike (Esox lucius) two phases of muscle
      differentiation can be distinguished. In the first phase, the somite cells
      derived stock, the primary myoblasts (of mesodermal origin), fuse to form
      multinucleate myotubes. Participation of myotomal cells of mesodermal origin is
      insufficient for further muscle development. In the second stage mesenchymal
      cells migrate, via myosepts, into the myotome between myotubes.
      Immunocytochemical detection of proliferating cell nuclear antigen (marker of S
      phase of cell cycle) showed their mitotic activity. Transmission electron
      microscope analysis revealed that the differentiation of these cells depends on
      their position. Cells remaining in the myosepts develop into fibroblasts and
      produce collagen fibres, while those that have migrated into the myotomes
      transform into secondary myoblasts. Mesenchymal cells in the studied species are
      believed to participate in hypertrophy and hyperplasy of muscle fibres. Thus the
      muscle fibres in pike (E. lucius) are of mesodermal-mesenchymal origin.

PMID- 16433679
TI  - Biology of estrogens in skin: implications for skin aging.
AB  - Estrogens have a profound influence on skin. The relative hypoestrogenism that
      accompanies menopause exacerbates the deleterious effects of both intrinsic and
      environmental aging. Estrogens clearly have a key role in skin aging homeostasis
      as evidenced by the accelerated decline in skin appearance seen in the
      perimenopausal years. Estrogens improve skin in many ways. Among these, they
      increase collagen content and skin thickness and improve skin moisture. However,
      despite the knowledge that estrogens have such important effects on skin, the
      cellular and subcellular sites and mechanisms of estrogen action are still poorly
      understood. Estrogen receptors (ERs) have been detected in skin, and recent
      studies suggest that estrogens exert their effect in skin through the same
      molecular pathways used in other non-reproductive tissues. Although systemic
      hormone replacement therapy (HRT) has been used for many years, recent trials
      have reported a significant increased risk of breast cancer and other pathologies
      with this treatment. This has led to reconsider the risks and benefits of HRT.
      For this reason, systemic HRT cannot be recommended today to treat skin aging.
      Currently, intensive research is conducted to develop new drugs called selective
      ER modulators (SERMs). These drugs exert mixed estrogenic and antiestrogenic
      effects depending on the tissue and cell type. One might expect in the future
      such a drug targeting specifically the skin without systemic side effects.

PMID- 16433680
TI  - CCL28 production in HaCaT cells was mediated by different signal pathways from
      CCL27.
AB  - Both CCL27 and CCL28 are ligands for CCR10 and attract CCR10(+) lymphocytes. We
      previously demonstrated that CCL27 and CCL28 were strongly expressed in sera and
      lesional keratinocytes of patients with atopic dermatitis and psoriasis vulgaris.
      However, the regulation of CCL27 and CCL28 production in keratinocytes has not
      been well documented. In this study, we showed that CCL27 and CCL28 expression
      and production by a human keratinocyte cell line, HaCaT cells, were strongly
      induced by inflammatory cytokines tumor necrosis factor-alpha and interleukin
      1beta. CCL27 production was downregulated by inhibitors of p38 mitogen-activated
      protein kinase and nuclear factor-kappa B (NF-kappaB). By contrast, CCL28
      production was downregulated by inhibitors of extracellular signal-regulated
      kinase and NF-kappaB. Our study results suggest that CCL28 produced by
      keratinocytes is mediated by different signal pathways from CCL27 and that both
      CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases.

PMID- 16433681
TI  - Delineation of diversified desmoglein distribution in stratified squamous
      epithelia: implications in diseases.
AB  - Desmogleins play critical roles in cell adhesion and skin blistering diseases, as
      they are the target antigens of autoimmune antibodies and bacterial toxins. We
      recently cloned several novel members of the desmoglein gene family, bringing the
      number of desmogleins to four in the rat and human genomes and six in the mouse.
      Here, we have produced a monoclonal antibody to a cytoplasmic epitope of Dsg4,
      assessed its specificity and compared it to several existing Dsg1-3 antibodies.
      We also demonstrated cross-reactivity of commercially available and often used
      Dsg1 antibodies. Using these tools, we delineated the unique expression patterns
      of each desmoglein isoform in various human and mouse stratified squamous
      epithelia, including skin, hair, palm, and oral mucosa. Interestingly, in the
      epidermis, the expression of each desmoglein correlates with their gene
      arrangement in the cadherin locus. In human, Dsg4 was detected primarily in the
      granular and cornified cell layers of the epidermis, while present throughout all
      differentiated layers of the oral mucosa and palm, and in the matrix cells of
      anagen hair bulb. Similar pattern of expression for Dsg4 was observed in mouse,
      with the exception that it was expressed at significantly lower levels in the
      mouse epidermis. These results demonstrate the complexity of desmoglein gene
      expression and provide additional insights into the correlation between tissue
      expression patterns and disease phenotypes.

PMID- 16433682
TI  - Expression of cathepsin L and its inhibitor hurpin in inflammatory and neoplastic
      skin diseases.
AB  - Cathepsin (Cat) L is an important lysosomal proteinase involved in a variety of
      cellular functions including intracellular protein turnover, epidermal
      homeostasis and hair development. Hurpin (serpinB13) is a cross-class specific
      serine protease inhibitor of Cat L. We have analysed the expression and
      localization of Cat L and hurpin in various inflammatory and neoplastic diseases
      by immunohistochemistry. Whereas Cat L expression in normal skin was below
      detection limit, immunoreactivity was detected in chronic inflammatory
      dermatoses. The highest expression of Cat L was found in psoriasis, atopic eczema
      and squamous cell carcinoma (SCC) samples. Samples of Lupus erythematosus,
      folliculitis, acne inversa, chronic leg ulcers and pyoderma gangrenosum
      demonstrated similar but lower expression for Cat L. In malignant cells of SCC,
      basal cell carcinoma and malignant melanoma, characteristic staining patterns
      were observed for Cat L, with more abundant expression at the periphery of the
      tumor. Expanding our previous work, we found that the expression of hurpin was
      confined mainly to the basal layer in normal skin samples, whereas hurpin was
      overexpressed and redistributed in diseased skin. The localization of hurpin in
      dermatoses and neoplasias differed from that in normal skin in that the highest
      expression was found in the outermost layers of the granular and upper spinous
      layers. Similarly to Cat L, the highest expression for hurpin was found in
      psoriasis and SCC. The results presented here summarize for the first time the
      expression of the protease Cat L and its inhibitor hurpin in a broad spectrum of
      skin diseases.

PMID- 16433683
TI  - Automated measurement of skin prick tests: an advance towards exact calculation
      of wheal size.
AB  - BACKGROUND: Using the Khoros image processing software environment, we developed
      a software-based system capable of extracting wheal size from skin prick tests
      (SPTs) in mm(2) for research and routine purposes. METHODS: At 20 min, the
      outlines of up to 20 wheals were marked with a pen and transferred with
      translucent adhesive tapes to a white paper form carrying predefined markings.
      The form was scanned at 200 dpi. The software automatically analysed the scanned
      image and calculated the sizes of the wheals. In a pilot study, serial SPTs with
      histamine in increasing dilutions were performed in 12 healthy volunteers in
      duplicate on both volar forearms. We matched the application results with a
      reference created from the scanned pictures. RESULTS: Bland-Altman analysis
      showed reference and software calculation reaching very high agreement. The
      comparison of reference/software resulted in a low centred coefficient of
      variation (COV) of 11.9%. This was superior to the conventional measurement of
      horizontal (COV 37.9%) or maximal/minimal diameter (COV 25.9%). CONCLUSION: We
      present an accurate tool for exactly calculating SPT wheal size in mm(2).

PMID- 16433684
TI  - Role of microchimerism in the pathogenesis of oral lichen planus.
AB  - OBJECTIVE: Microchimerism of persistent fetal cells has been implicated in some
      cell-mediated autoimmune diseases. This study examines the hypothesis that fetal
      microchimerism plays a role in the pathogenesis of lichen planus (LP) affecting
      the oral cavity. STUDY DESIGN: Mucosal biopsies of 12 women with oral LP (OLP)
      were tested for the presence of both male cells and male DNA originating from
      prior pregnancies or prior blood transfusions. Six male patients with OLP served
      as a control group. Biopsies were analyzed for the presence of Y-chromosome
      positive cells by fluorescence in situ hybridization (FISH) with X- and Y
      specific DNA probes. To confirm the FISH findings, we used fluorescent polymerase
      chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from
      mucosal lesions. RESULTS: Using FISH technology, all the 18 biopsy samples showed
      good hybridization results. In females, Y-chromosome-specific signals were not
      detected by FISH at any site of the lesions. PCR amplification demonstrated a
      single peak at the locus specific for the X-chromosome. CONCLUSION: Male DNA
      microchimerism was not present in any of the investigated lesions, suggesting
      that microchimerism because of persisting male fetal cells is unlikely to play a
      major role in the pathogenesis of OLP.

PMID- 16433685
TI  - Infrared radiation induces the p53 signaling pathway: role in infrared prevention
      of ultraviolet B toxicity.
AB  - We have previously observed that preirradiation with naturally occurring doses of
      near-infrared (IR) protects normal human dermal fibroblasts from ultraviolet (UV)
      cytotoxicity in vitro. This effect was observed in temperature-controlled
      conditions, without heat shock protein (Hsp72-70) induction. Moreover, IR
      inhibited UVB-induced apoptosis by modulating the Bcl2/Bax balance, pointing to a
      role of p53. Here, we show for the first time that p53-deficient SaOs cells are
      not protected from UVB cytotoxicity by IR preirradiation, suggesting that the
      response to IR is p53-dependent. Thus, we investigated the effect of IR on the
      p53 signaling pathway. Normal human dermal fibroblasts exposed in vitro to IR
      accumulated p53 protein, involving p53 stabilization and phosphorylation of
      serine 15 (Ser15) and Ser20. IR-induced p53 accumulation correlated with
      increased expression of p21 and GADD45, showing that IR also stimulates p53
      transcriptional activity. By modulating UVB-induced targets of the p53 signaling
      pathway, IR irradiation appears to anticipate the UVB response and to prepare
      cells to better resist subsequent UV-induced stress. This is reinforced by the
      fact that IR preirradiation reduces the formation of UVB-induced thymine dimers.

PMID- 16433686
TI  - Low systemic exposure in infants with atopic dermatitis in a 1-year
      pharmacokinetic study with pimecrolimus cream 1%*.
AB  - Systemic drug exposure following the application of topical agents is a very
      important safety consideration, particularly in infants, who have a significantly
      higher ratio of body surface area to body mass than older children and adults.
      Here, we report on drug exposure in five infants aged 5.7-11.9 months at
      baseline, with extensive, moderate-to-severe atopic dermatitis (AD). Patients
      were treated bid for 1 year, as needed, with pimecrolimus cream 1% in an open
      label, non-controlled study. No indication of drug accumulation was found;
      pimecrolimus blood concentrations were consistently low, ranging from below the
      limit of quantitation (0.1 ng/ml) to 1.94 ng/ml. Treatment over this prolonged
      period was well tolerated, with no evidence of any treatment-related adverse
      events. The results of this 1-year study indicate that long-term management of AD
      with pimecrolimus cream 1% is associated with consistently very low systemic
      absorption, even in the youngest patients with extensive disease.

PMID- 16433688
TI  - Ultrasound detection of placental insufficiency in women with 'unexplained'
      abnormal maternal serum screening results.
AB  - Serious placental insufficiency results in perinatal death or preterm birth from
      ischemic-thrombotic pathology, a process which has its origins in placental
      maldevelopment in the first trimester. A proportion of at-risk pregnancies may be
      identified from abnormalities in first or second trimester serum screening data,
      uterine artery Doppler waveforms or placental shape and texture at the time of
      the 18-20-week anatomical examination. In combination, these tests may be capable
      of recognizing a subset of at-risk pregnancies with 50% positive predictive
      values. Early recognition before fetal viability affords opportunities to direct
      women to regional perinatal care centres for enhanced maternal-fetal
      surveillance, corticosteroids to enhance fetal lung maturation, prophylactic
      measures to prevent pre-eclampsia and optimal decision making around the time of
      delivery. The creation of regional screening programs to use screening data with
      a placental focus is likely to be cost-effective, because existing patterns of
      care are utilized. More importantly, this strategy can direct women to
      participate in clinical research programs designed to reduce morbidity and
      mortality from this common group of conditions.

PMID- 16433689
TI  - Vesicoureteric reflux and renal malformations: a developmental problem.
AB  - Vesicoureteric reflux (VUR) is a congenital urinary tract defect caused by the
      failure of the ureter to insert correctly into the bladder. It occurs in up to 1%
      of the general population and is associated with recurrent urinary tract
      infections and renal failure. Despite treatment of affected children for the past
      40 years, the incidence of end-stage renal disease secondary to VUR has not
      decreased. Twin and family studies reveal that VUR has a genetic basis. Some of
      the gene candidates that have been identified regulate the position of ureteric
      budding, a critical step in both kidney and urinary tract development. Analysis
      of data from humans and mice suggests that some of the renal damage associated
      with VUR is congenital and is due to a kidney malformation. Therefore, in these
      cases, the association of VUR and renal failure may be caused by a genetic defect
      affecting the formation of the kidney and the urinary tract.

PMID- 16433693
TI  - 15q duplication associated with autism in a multiplex family with a familial
      cryptic translocation t(14;15)(q11.2;q13.3) detected using array-CGH.
AB  - Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with
      a strong genetic aetiology. In approximately 1% of cases, duplication of the
      15q11-13 region has been reported. We report the clinical, array-comparative
      genomic hybridization (CGH) and cytogenetic evaluation of two individuals from a
      multiplex family demonstrating autism due to a maternally inherited gain of 15q11
      13. Our findings indicate that unlike most 15q11-13 gains, which are caused by
      interstitial duplication of this region or supernumerary marker chromosomes
      deriving from proximal 15q, the 15q gain in this family is the result of abnormal
      segregation of a cryptic familial translocation with breakpoints at 14q11.2 and
      15q13.3. The affected members of this family were found to have a normal
      karyotype at >550 band resolution. This translocation was identified using the 1
      Mb resolution whole genome array (Spectral Genomics). The affected individuals
      have a gain of seven clones from proximal 15q, a loss of two clones from proximal
      14q and a gain of two clones from 6q. Fluorescent in situ hybridization (FISH)
      analysis with clones from chromosomes 14 and 15, combined with DAPI reverse
      banding, showed an abnormal karyotype with one normal chromosome 15 and the
      der(15) t(14;15)(q11.2.;q13.3), resulting in the gain of proximal 15q and the
      loss of proximal 14q in affected individuals. The duplication of two clones from
      6q in the affected subjects was also found in unaffected members of the family.
      Our findings suggest that the gain of 15q in autism may in some cases be due to
      cryptic translocations with breakpoints in the pericentromic regions of
      chromosome 15 and a different acrocentric chromosome. Variation in the size of
      pericentromic regions of any acrocentric chromosome may justify karyotype and
      FISH studies of autistic probands and their parents using probes from the 15q
      proximal region to determine recurrence risk for autism in some families.

PMID- 16433694
TI  - Molecular investigation and long-term clinical progress in Greek Cypriot families
      with recessive distal renal tubular acidosis and sensorineural deafness due to
      mutations in the ATP6V1B1 gene.
AB  - The spectrum of distal renal tubular acidosis (dRTA) includes a genetically
      heterogeneous group of inherited conditions of both autosomal-dominant and
      recessive mode of inheritance. The basic defect is linked to the renal part of
      acid-base homeostasis, which is partly achieved by the regulated luminal
      secretion of H+ at the apical surface of the alpha-intercalated cells of renal
      collecting ducts. This is coupled to bicarbonate reabsorption with chloride
      counter transport across the basolateral membranes. Here, we describe the
      molecular findings of the first two Greek Cypriot families with recessive dRTA
      and the long-term clinical findings in four of five affected members. DNA linkage
      analysis with four polymorphic markers flanking the ATP6V1B1 gene on chromosome 2
      gave evidence for positive linkage; direct DNA analysis by automated DNA
      sequencing revealed that patients in one family were homozygous for mutation
      229+1G>T (IVS7+1G>T) and that patients in the second family were compound
      heterozygous for 229+1G>T and R157C. The mutations were found on four different
      haplotypes. Both the mutations were previously reported in patients of Turkish
      origin. Three known polymorphic variants were also identified. The five patients
      demonstrated the whole clinical spectrum of the disease including death in
      infancy, failure to thrive, rickets, nephrocalcinosis, nephrolithiasis, and
      episodes of hypokalemic paralysis. Some of the family members are now in their
      mid 30s and late 20s, and nephrolithiasis with recurrent renal colics is their
      main problem. Renal function has remained normal. In conclusion, early diagnosis
      in infancy and prompt treatment with alkali and potassium supplements is of great
      benefit to the patient with dRTA and ensures normal growth. The identification of
      responsible mutations facilitates antenatal or postnatal diagnosis in concerned
      families and improves the prognosis.

PMID- 16433695
TI  - Quantification of all fetal nucleated cells in maternal blood in different cases
      of aneuploidies.
AB  - We quantified all fetal nucleated cells (FNCs) per unit volume of maternal blood
      in different aneuploid pregnancies using molecular cytogenetic techniques. Seven
      cases of male trisomy 18, two triploidies (69,XXX), two 47,XXX, one 47,XXY, one
      47,XYY, one male trisomy 13, and one case of 47,XY,r(22),+r(22) were analyzed.
      Whole blood samples were obtained from 15 women between 17 and 29 gestational
      weeks and harvested without using fetal cell enrichment procedures. Fluorescence
      in situ hybridization and primed in situ labeling were performed to identify the
      FNCs. All slides were manually scanned to quantify those cells. We have
      identified 4-20 FNCs/ml of maternal blood in the cases of trisomy 18; 10 and 25
      FNCs/ml in the two cases of triploidy; 16 and 14 FNCs/ml, respectively, in the
      two X trisomies; 19 FNCs/ml in the 47,XXY; 26 FNCs/ml in the 47,XYY; nine FNCs/ml
      in the trisomy 13; and 10 FNCs/ml in the case of r(22). To detect all FNCs in all
      aneuploid pregnancies, we have used a very simple method that minimizes the
      manipulation steps to avoid losing fetal cells. The number of FNCs identified in
      aneuploid pregnancies was 2-5 times higher than in normal pregnancies. This
      higher number of FNCs will favor the design of a non-invasive pre-natal test.

PMID- 16433696
TI  - Prevalence of HFE C282Y and H63D in Jewish populations and clinical implications
      of H63D homozygosity.
AB  - The frequencies of C282Y and H63D mutations of the HFE gene vary between
      different populations. A previous study showed an unexpectedly high H63D
      frequency in Chuetas (a population of Jewish descent). The present study
      addressed the question of the distribution of these mutations in Jewish
      populations from different origins and studied the possible causes of the high
      H63D frequency in Chuetas. Moreover, to improve the understanding of the
      controversial relationship between H63D homozygosity and iron overload, a group
      of patients with altered iron metabolism were studied. The high frequency of H63D
      mutation in Chuetas is not due to a high prevalence of this mutation in Sephardic
      Jews. Jewish populations have low C282Y and moderate H63D frequencies, suggesting
      slight gene flow from their surrounding populations. In accordance with
      historical and demographic data, genetic drift is the most probable cause for the
      singular H63D frequency in Chuetas. Clinically, this study of H63D homozygotes
      supports the conclusion that this genotype must be taken into account, because it
      confers an increased risk of iron overload and therefore genetic susceptibility
      to developing hereditary hemochromatosis or to aggravating other diseases.

PMID- 16433698
TI  - Evaluation of two different models to predict BRCA1 and BRCA2 mutations in a
      cohort of Danish hereditary breast and/or ovarian cancer families.
AB  - To meet the increasing demand for BRCA1 and BRCA2 mutation analysis, a robust
      system for selecting families who have a higher chance of a mutation has become
      important. Several models have been developed to help predict which samples are
      more likely to be mutation positive than others. We have undertaken a complete
      BRCA1 and BRCA2 mutation analysis in 267 Danish families with high-risk family
      history. We found deleterious mutations in 28% (76) of the families, 68% (52) of
      those in BRCA1 and 32% (24) in BRCA2. We compared our results with two popular
      manual models developed to estimate the chance of a positive result. One is the
      recently published Manchester model and the other is the Frank 2 model updated by
      Myriad Genetic Laboratories, Inc. Neither of the models would have suggested
      screening all mutation-positive samples. The Manchester model would have
      suggested screening 124 of the families in the cohort, thereby detecting 54 of 76
      mutations (sensitivity 71%; specificity 63%), whereas the Frank 2/Myriad model
      would have found 60 of 76 mutations by screening 169 samples if a 10% likelihood
      was adapted (sensitivity 79%; specificity 43%). The updated Manchester model
      suggested screening 172 families whereby 64 mutations would have been detected
      (sensitivity 84%; specificity 44%). We conclude that although both models would
      have reduced the number of samples screened significantly, up to 28% of the
      mutations would not have been found by applying these models to this Danish
      cohort of families. This raises the question whether models designed for specific
      populations can be used in a wider setting.

PMID- 16433699
TI  - Familial carpal tunnel syndrome: further evidence for a genetic contribution.

PMID- 16433697
TI  - Educational outcomes of a workplace screening program for genetic susceptibility
      to hemochromatosis.
AB  - Education is an essential component of a genetic screening program. Knowledge
      outcomes were measured after large-scale workplace education and screening for
      genetic susceptibility to hereditary hemochromatosis. The aim was to assess
      knowledge of concepts presented, impact of mode of delivery, and knowledge
      retention. Education in a group setting was delivered via oral or video
      presentation and knowledge assessed using self-administered questionnaires at
      baseline, 1 month, and 12 months. Over 60% of 11 679 participants correctly
      answered all questions at baseline, scoring higher with clinical concepts
      (disease etiology and treatment) than genetic concepts (penetrance and genetic
      heterogeneity). Revising the education program significantly increased correct
      responses for etiology (p < 0.002), whilst modifying the knowledge assessment
      tool significantly increased correct responses for etiology (p < 0.001) and gene
      penetrance (p < 0.001). For three of the four concepts assessed, use of video was
      as effective as oral presentation for knowledge outcomes. A significantly higher
      proportion of those at increased risk of disease (n = 44) responded correctly at
      12 months than did controls (n = 82; p = 0.011 for etiology, p = 0.002 for
      treatment and p = 0.003 for penetrance). Hence, genetic screening can be
      successfully offered in a group workplace setting, with participants remembering
      clinical concepts better than genetic concepts up to 1 year later.

PMID- 16433700
TI  - Multiple gynecologic tumors as rare associated phenotypes of FAP/Gardner syndrome
      in a family with the novel germline mutation in the APC gene.

PMID- 16433702
TI  - Molecular characterization of a balanced chromosome translocation in psoriasis
      vulgaris.

PMID- 16433701
TI  - Two clinical forms of glycogen-storage disease type II in two generations of the
      same family.

PMID- 16433703
TI  - Corino Andrade (1906-2005): a clinical geneticist before its own time.

PMID- 16433706
TI  - Fenofibrate and cardiovascular risk: a synopsis and commentary on (FIELD).

PMID- 16433707
TI  - Interventions to promote optimal health outcomes in children with Type 1 diabetes
      -are they effective?
AB  - The incidence of Type 1 diabetes is increasing worldwide, imposing enormous
      public health costs, as well as profoundly affecting individual quality of life.
      There is evidence that psychological problems are increased in children with
      diabetes and this morbidity is often associated with poor metabolic control.
      Specific risk factors for this dual morbidity are emerging from empirical
      studies. The next challenge is to identify effective interventions for use with
      children at risk for adverse mental and physical health outcomes. The
      intervention literature is reviewed. It is noted that most studies have used
      diabetes-specific, unstandardized interventions in groups of adolescents, with
      few interventions trialled with younger children. No study has targeted a
      specific psychological disorder such as behaviour problems or depression, both of
      which are known to be increased in children with diabetes and for which effective
      standardized interventions are available. Attention is drawn to methodological
      limitations in many of the studies conducted to date and suggestions made to
      reduce these in future interventions attempting to reduce the burden of illness
      in children with diabetes.

PMID- 16433709
TI  - The effect of obesity on glycaemic response to metformin or sulphonylureas in
      Type 2 diabetes.
AB  - AIMS: In treating Type 2 diabetes (T2DM), UK guidelines recommend metformin in
      obese and overweight patients, and either sulphonylureas or metformin in normal
      weight patients. Although other factors influence prescribing choice, a key
      objective in treating T2DM is to lower plasma glucose. There is little data on
      how glycaemic response to oral agents varies with body mass index (BMI).
      Therefore, we assessed current prescribing practice and effect of BMI on
      glycaemic response to sulphonylureas and metformin in a large population T2DM
      cohort. METHODS: BMI was determined in 3856 T2DM patients on sulphonylurea or
      metformin monotherapy in 2001-2002. Patients were identified from the Diabetes
      Audit and Research in Tayside, Scotland (DARTS) database. In a linear regression,
      the effect of BMI and other confounders on drug response was assessed in 2064
      treatment-naive patients commencing sulphonylureas or metformin between 1994 and
      2002. RESULTS: In 2001-2002, metformin was more likely to be used in obese than
      non-obese patients: 13% normal weight, 33.6% overweight and 62.1% obese patients
      were treated with metformin. Glycaemic response to sulphonylureas was not
      influenced by BMI (P = 0.81). Metformin was more effective in lowering glucose in
      those with a lower BMI (r = -0.02, P = 0.02), although the clinical impact of
      this was small. The HbA(1c) reduction in non-obese patients was similar to that
      in obese patients (1.46% vs. 1.34%, P = 0.11). CONCLUSIONS: Glycaemic response to
      metformin in non-obese and obese patients is similar, suggesting that an
      individual's BMI should not influence the choice of oral agent. Given the non
      glycaemia-related benefits of metformin, it should be used in more non-obese
      patients than is current practice in Tayside, Scotland.

PMID- 16433708
TI  - Mobile diabetes education and care: intervention for children and young people
      with Type 1 diabetes in rural areas of northern Germany.
AB  - AIMS: To improve the quality of care in children with Type 1 diabetes who have
      limited access to specialized diabetes care in rural areas, by providing a mobile
      diabetes education and care team, affiliated with a University hospital
      paediatric diabetes centre. METHODS: A cohort of 107 children and their families
      from eight rural hospitals was followed between July 2000 and July 2002.
      Parameters on quality of metabolic control (HbA(1c), hospitalization rate and
      number of episodes of severe hypoglycaemia), diabetes knowledge and quality of
      life at baseline (t(0)), 6 weeks (t(1)) and 6 months (t(2)) after the
      interventions were measured. RESULTS: Mean HbA(1c) was 7.9 +/- 1.4% at t(0). The
      proportion of HbA(1c) values < 6.8% increased significantly (P < 0.05) and of
      values > 8.0% decreased significantly (P < 0.01) at t(1) and t(2). The rate of
      hospitalization fell significantly by 9.4%, from 16.2% at baseline to 6.8% at
      t(2) (P < 0.05). The children reported significantly better diabetes-specific
      quality of life (P < 0.05) and higher self-esteem (P < 0.01) after the
      intervention. Theoretical diabetes knowledge was increased both in the short and
      long term (P < 0.05). CONCLUSIONS: The intervention improved metabolic control,
      diabetes knowledge and diabetes-specific quality of life. We conclude that high
      quality diabetes care in a rural area can be provided by a mobile diabetes
      education and care team.

PMID- 16433710
TI  - Meal-induced platelet activation in Type 2 diabetes mellitus: effects of
      treatment with repaglinide and glibenclamide.
AB  - AIMS: To compare the effects of treatment with repaglinide and glibenclamide on
      platelet function and endothelial markers in patients with Type 2 diabetes
      mellitus, before and after a standardized meal. METHODS: Fifteen patients with
      Type 2 diabetes were investigated on three occasions: at baseline without oral
      hypoglycaemic drug treatment, and after 6 weeks' treatment with repaglinide or
      glibenclamide, respectively, in an open randomized cross-over study. Agonist
      induced platelet P-selectin expression and platelet aggregation, urinary
      thromboxane, soluble P-selectin, von Willebrand factor (VWF), soluble E-selectin,
      intercellular adhesion molecule (ICAM-1) and C-reactive protein (CRP) were
      measured. In addition, pre-meal data were compared with non-diabetic control
      subjects (n = 15), matched for sex, age and BMI. RESULTS: Adenosine diphosphate
      (ADP)-induced platelet P-selectin expression increased post-meal in Type 2
      diabetic patients both at baseline and after treatment with repaglinide and
      glibenclamide (P < 0.01 for all; repeated measures anova). Repaglinide treatment
      reduced fasting ADP-induced P-selectin expression compared with baseline (P =
      0.01), but did not influence meal-induced platelet hyper-reactivity (P = 0.32).
      No significant anti-platelet effects of glibenclamide treatment were found.
      Plasma concentrations of VWF and ICAM-1 were elevated in patients with Type 2
      diabetes compared with control subjects (P < 0.05 for both) and were reduced
      during treatment with repaglinide (P < 0.01 for both) but did not change during
      glibenclamide treatment. CONCLUSIONS: The post-meal state is associated with
      enhanced platelet reactivity in patients with Type 2 diabetes mellitus. Pre-meal
      treatment with repaglinide or glibenclamide does not inhibit postprandial
      platelet activation, but repaglinide treatment is associated with attenuated
      platelet and endothelial activity in the fasting state.

PMID- 16433711
TI  - Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and
      NPH-based multiple daily insulin injections (MDI) on glycaemic control and
      quality of life: results of the 5-nations trial.
AB  - AIMS: The goal of the study was to determine whether continuous subcutaneous
      insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen
      based on neutral protamine hagedorn (NPH) as basal insulin with respect to
      glycaemic control and quality of life in people with Type 1 diabetes. METHODS:
      The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11
      European centres. Two hundred and seventy-two patients were treated with CSII or
      MDI during a 2-month run-in period followed by a 6-month treatment period,
      respectively. The quality of glycaemic control was assessed by HbA(1c), blood
      glucose values, and the frequency of hypoglycaemic events. For the evaluation of
      the quality of life, three different self-report questionnaires have been
      assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P <
      0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less
      fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P <
      0.001). There was a marked reduction in the frequency of hypoglycaemic events
      using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence
      interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe
      hypoglycaemia, respectively. The overall score of the diabetes quality of life
      questionnaire was higher for CSII (P < 0.001), and an improvement in pump users'
      perception of mental health was detected when using the SF-12 questionnaire (P <
      0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for
      individuals with Type 1 diabetes, with improvement in all significant metabolic
      parameters as well as in patients' quality of life. Additional studies are needed
      to compare CSII with glargine- and detemir-based MDI.

PMID- 16433712
TI  - Diabetes mellitus and impaired glucose regulation in the Canary Islands (Spain):
      prevalence and associated factors in the adult population of Telde, Gran Canaria.
AB  - AIMS: To estimate the prevalence and the determinants of diabetes mellitus and
      impaired glucose regulation (IGR) in an adult Canarian population. METHODS: Cross
      sectional study. One thousand and thirty subjects aged 30-82 years were randomly
      selected. Participants completed a survey questionnaire and underwent blood
      pressure measurements, anthropometry, blood samples, and a 75-g standardized oral
      glucose tolerance test. RESULTS: The age-standardized prevalence of diabetes was
      15.8% (95% confidence interval: 11.8-19.8) in men and 10.6% (7.1-14.1) in women.
      Total prevalence was 13.2% (11.1-15.2). Among individuals with diabetes, 55.4% of
      men and 38.2% of women were not previously diagnosed. The age-standardized
      prevalences of impaired glucose tolerance and impaired fasting glycaemia were
      11.4% (9.5-13.4) and 2.8% (1.8-3.8), respectively. In multivariate analyses, age,
      waist circumference, serum triglycerides, and familial history of diabetes were
      independently associated with diabetes in both sexes, while a value of C-reactive
      protein (CRP) >/= 1 mg/l showed an association with diabetes, but only in men.
      Age and triglycerides were related to impaired glucose regulation (IGR) in both
      sexes, waist circumference was related to IGR exclusively in men, and familial
      diabetes exclusively in women. Statistically significant interactions between
      gender and both CRP and triglycerides were found with respect to diabetes, and
      between gender and both waist circumference and triglycerides for IGR.
      CONCLUSIONS: Compared with the rest of Spain, the prevalence of diabetes is
      moderately increased in this area of the Canary Islands. Along with other well
      established risk factors, CRP was independently associated with diabetes, but
      only in the male population.

PMID- 16433713
TI  - Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus.
AB  - AIMS: The hypothesis was tested in an exploratory study that individuals at high
      risk of developing Type 1 diabetes mellitus have altered systemic levels of
      cytokines and chemokines. SUBJECTS AND METHODS: Forty-two non-diabetic first
      degree relatives of patients with Type 1 diabetes mellitus were recruited. Of
      these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid
      decarboxylase antibody, IA-2 antibody). Follow-up for 9-11 years confirmed high
      vs. moderate diabetes risk in islet autoantibody-positive vs. -negative
      relatives. Cytokines and chemokines were determined by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Serum concentrations of classic Th1
      associated cytokines (IFN-gamma, IL-12, IL-18) or Th2/Treg-associated cytokines
      (IL-5, IL-10, IL-13) did not significantly differ in high vs. moderate diabetes
      risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were
      increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in
      the multiple islet autoantibody-positive group. No significant differences were
      seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two
      closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P =
      0.00005), but not in the autoantibody-negative group. CONCLUSION: Relatives at
      high risk of developing Type 1 diabetes mellitus have abnormal cellular immune
      regulation at the level of systemic chemokines. The up-regulation of CCL3 and
      CCL4 vs. down-regulation of CCL2 suggests opposed functions of these chemokines
      in the disease process. These findings need to be confirmed by independent
      studies.

PMID- 16433715
TI  - Plasma anhydro-D-glucitol (1,5-AG) as an indicator of hyperglycaemic excursions
      in pregnant women with diabetes.
AB  - AIMS: To evaluate the use of the plasma 1,5-anhydro-d-glucitol (1,5-AG) level as
      a possible marker for glucose excursions in pregnant women with diabetes.
      METHODS: The study group consisted of 55 pregnant women with diabetes
      (gestational diabetes mellitus-GDM, n = 28 or pre-gestational diabetes mellitus 
      PGDM, n = 27), without hepatic or renal insufficiency, gestational age range 5-38
      weeks. In each patient, 24-h glucose profile, glycated haemoglobin and 1,5-AG
      plasma levels were measured. Mean blood glucose (MBG) and M-value (by
      Schlichtkrull) were calculated. MBG, M-value and maximal daily glycaemia (MxG)
      were used as indexes of daily glycaemic excursions. RESULTS: A significant
      correlation was found between the 1,5-AG plasma level and MxG [r = (-0.3)] and
      between the 1,5-AG level and M-value [r = (-0.36)]. There was no association
      between the 1,5-AG level and gestational age. Multivariate regression analysis,
      with 24-h glucose profile, gestational age and MxG as independent variables,
      showed that MxG was the main parameter determining the 1,5-AG plasma level [beta
      = (-0.68)]. The M-value, the coefficient of glucose fluctuations, also determined
      the 1,5-AG level but with lower statistical power [beta = (0.41)]. No statistical
      differences were found in the group with HbA(1c) < 6% or > 6% for 1,5-AG and M
      value, while MBG was higher in poorly controlled patients (HbA(1c) > 6%).
      CONCLUSIONS: The plasma 1,5-AG level may be a useful marker of daily glucose
      excursion in pregnant women with diabetes, as an adjunct to HbA(1c) monitoring.

PMID- 16433714
TI  - Patient-centred and professional-directed implementation strategies for diabetes
      guidelines: a cluster-randomized trial-based cost-effectiveness analysis.
AB  - AIMS: Economic evaluations of diabetes interventions do not usually include
      analyses on effects and cost of implementation strategies. This leads to
      optimistic cost-effectiveness estimates. This study reports empirical findings on
      the cost-effectiveness of two implementation strategies compared with usual
      hospital outpatient care. It includes both patient-related and intervention
      related cost. PATIENTS AND METHODS: In a clustered-randomized controlled trial
      design, 13 Dutch general hospitals were randomly assigned to a control group, a
      professional-directed or a patient-centred implementation programme.
      Professionals received feedback on baseline data, education and reminders.
      Patients in the patient-centred group received education and diabetes passports.
      A validated probabilistic Dutch diabetes model and the UKPDS risk engine are used
      to compute lifetime disease outcomes and cost in the three groups, including
      uncertainties. RESULTS: Glycated haemoglobin (HbA(1c)) at 1 year (the measure
      used to predict diabetes outcome changes over a lifetime) decreased by 0.2% in
      the professional-change group and by 0.3% in the patient-centred group, while it
      increased by 0.2% in the control group. Costs of primary implementation were < 5
      Euro per head in both groups, but average lifetime costs of improved care and
      longer life expectancy rose by 9389 Euro and 9620 Euro, respectively. Life
      expectancy improved by 0.34 and 0.63 years, and quality-adjusted life years
      (QALY) by 0.29 and 0.59. Accordingly, the incremental cost per QALY was 32 218
      Euro for professional-change care and 16 353 for patient-centred care compared
      with control, and 881 Euro for patient-centred vs. professional-change care.
      Uncertainties are presented in acceptability curves: above 65 Euro per annum the
      patient-directed strategy is most likely the optimum choice. CONCLUSION: Both
      guideline implementation strategies in secondary care are cost-effective compared
      with current care, by Dutch standards, for these patients. Additional annual
      costs per patient using patient passports are low. This analysis supports patient
      involvement in diabetes in the Netherlands, and probably also in other Western
      European settings.

PMID- 16433716
TI  - Identifying the impact of diabetes research.
AB  - AIMS: Assessment of the impact of health research is a growing but problematic
      field. We examined how a combination of approaches might together inform
      assessment of the impact of a body of diabetes research published in 1981 and
      help identify factors behind success. METHODS: Three broad approaches were
      applied to the work of one team leader of acknowledged influence. Standard
      bibliographic analysis was complemented by a second approach which categorized
      the importance of the primary publications to the papers citing them, in four
      domains. In parallel, a third approach involved qualitative assessment using
      surveys, critical pathway analysis by, and interviews of, co-authors and external
      experts. Extending the approach incorporated key additional publications from
      other years. RESULTS: In 1981, the team leader published 29 papers. Citations to
      these 29 first generation papers varied from 1 to 76 and resulted in 799 second
      generation papers. Citations to these produced 12 891 third generation papers.
      Analysis of second generation papers suggested the cited first generation paper
      was thought to be of considerable or essential significance in only 9% of cases.
      While much research made little impact, qualitative analysis included a wealth of
      information, sometimes missed by standard bibliographic techniques, on where the
      identified research influenced important streams of clinical development.
      Analysis covered major research studies (such as the Diabetes Control and
      Complications Trial), insulin pump therapy, and career development of co-authors.
      CONCLUSIONS: Understanding the impact of research requires multiple approaches.
      With refinement, these techniques could be employed more widely and potentially
      could inform research policy.

PMID- 16433717
TI  - Prevalence and risk factors for asymptomatic bacteriuria in women with Type 2
      diabetes mellitus.
AB  - AIMS: Asymptomatic bacteriuria (ASB) has been considered as a complication in
      diabetic women. The reported data on the prevalence and various risk factors for
      ASB appear to be conflicting. Consequently, we investigated the prevalence and
      major risk factors of ASB in women with Type 2 diabetes mellitus. METHODS: A
      total of 411 non-pregnant women (aged 59.6 +/- 10.8 years) with Type 2 diabetes,
      and 160 women without diabetes (aged 53.3 +/- 15.1 years) assigned as controls,
      attending an outpatient endocrine clinic in a university-affiliated teaching
      hospital, were included. All participating women were interviewed and screened
      for the presence of ASB. In all participants, fasting blood glucose, HbA(1c) and
      renal function were measured. Complications of diabetes were also assessed.
      RESULTS: Of the 411 diabetic women, 25 (6.1%) had ASB, compared with four of 160
      (2.5%) in control women (P = 0.07). Independent risk factors for the presence of
      ASB were albuminuria > 150 mg/24 h [odds ratio (OR) 4.96 (95% CI 1.64-15.0, P =
      0.005)] and serum creatinine [OR 3.5 (95% CI 1.4-8.8, P = 0.008)]. No significant
      association was evident with age, BMI, duration of disease, glycaemic control
      assessed by HbA(1c) or chronic complications of diabetes, namely macrovascular
      disease, neuropathy and retinopathy. CONCLUSIONS: Women with Type 2 diabetes are
      not at higher risk of developing ASB than non-diabetic women. Independent and
      significant risk factors for ASB are macroalbuminuria and serum creatinine. The
      low prevalence of ASB found in this study may be as a result of the ethnic origin
      of these women and the circumcised state of their partners.

PMID- 16433718
TI  - Diabetes prevalence in England, 2001--estimates from an epidemiological model.
AB  - AIMS: To estimate the total prevalence of diabetes mellitus (diagnosed and
      undiagnosed) at national, regional and local level in England to support health
      care planning and delivery. METHODS: An epidemiological model was constructed by
      applying age-sex-ethnic-specific reference prevalence rates from epidemiological
      studies to resident populations (2001 census) of England at national, regional,
      and local authority/Primary Care Trust levels. RESULTS: Estimated prevalence of
      total diabetes for all persons in England was 4.41% in 2001, equating to 2 168
      000 persons. Type 2 diabetes was estimated to affect 2 002 000 persons (92.3%)
      and Type 1 diabetes 166 000 persons (7.7%). Diabetes prevalence was estimated to
      be higher in women (5.17%) than men (3.61%). People from ethnic minority groups
      had higher crude prevalence than White Europeans (4.29, 5.69, 6.63 and 2.13%
      among White Europeans, Black African/Caribbeans, South Asians and 'other' groups,
      respectively). Prevalence increased sharply with age (0.33, 3.37 and 13.92%,
      respectively, in those aged 0-29, 30-59 and 60+ years). The model allows use of
      user-defined population denominator estimates to derive numbers and prevalence of
      people with diabetes for a given local population group, such as at ward or
      general practice level. CONCLUSIONS: Self-reported diabetes prevalence estimates
      from community surveys underestimate the true burden of diabetes. The model can
      be used to derive the expected total prevalence of diabetes in health areas that
      lack reliable data to facilitate the implementation of the National Service
      Framework for diabetes. It will also allow estimates of future diabetes
      prevalence to be derived, and can potentially be used for prevalence estimates in
      all of the UK.

PMID- 16433719
TI  - Prevalence of erectile dysfunction in Korean men with Type 2 diabetes mellitus.
AB  - AIMS: We investigated the prevalence and risk factors for developing erectile
      dysfunction (ED) in 1312 Korean men with diabetes in a multicentre study.
      METHODS: We used the modified International Index for Erectile Function-5
      criteria to identify mild, moderate and complete ED. A standardized face-to-face
      questionnaire was used by trained interviewers, and validated against telephone
      interviews. We recorded the duration of diabetes, level of glycaemic control,
      vital signs, complications, exercise and alcohol and smoking habits, and diabetes
      treatments used. Results The mean age and median duration of diabetes were 53.8
      +/- 6.65 and 6 years (range 1-43), respectively. The mean HbA(1c) and fasting
      glucose levels were 7.9 +/- 1.65% and 8.6 +/- 2.82 mmol/l, respectively. The
      overall prevalences of mild, moderate, complete ED and all ED (mild-to-complete)
      were 20.1, 19.5, 25.8 and 65.4%, respectively. ED was more common with age,
      reaching 79.3% in men aged > 60 years. Subjects aged > 60 years and with a
      duration of diabetes > 10 years were at greatest risk for all ED (OR = 10.4, 95%
      CI 5.8-18.5, P < 0.001) and complete ED (OR = 13.2, 95% CI 7.3-23.9, P < 0.001)
      when compared with the reference group (age 40-50 years with duration < 6 years).
      Age, duration of diabetes, HbA(1c), insulin use, neuropathy and macrovascular
      complications were positively associated with ED, but alcohol consumption and
      exercise habits were negatively associated. CONCLUSIONS: The prevalence of
      complete ED was approximately six times higher than in the general population.

PMID- 16433721
TI  - Measurement of microvolt T-wave alternans, a new arrhythmic risk stratification
      test, in Type 2 diabetic patients without clinical cardiovascular disease.
AB  - AIMS: Patients with a positive microvolt T-wave alternans (TWA) are at increased
      risk of ventricular arrhythmias and sudden cardiac death. Although Type 2
      diabetes is associated with an increased risk of these events, there is a dearth
      of available data on measurements of TWA in people with Type 2 diabetes. METHODS:
      We studied 43 Type 2 diabetic volunteers who were free of diagnosed
      cardiovascular disease (CVD). Microvolt TWA analysis was performed non-invasively
      using the CH 2000 system during submaximal exercise with the patients sitting on
      a bicycle ergometer. RESULTS: TWA analysis was positive in 9 (21%) patients,
      negative in 32 (74.4%) and indeterminate in 2 (4.6%) subjects. TWA positive
      patients had significantly higher HbA(1c) levels than those with TWA negativity
      (8.1 +/- 0.9 vs. 7.2 +/- 0.8%, P < 0.01). Age, sex, BMI, blood pressure, lipids,
      24-h heart rate variability, QTc interval duration, smoking history, diabetes
      duration and treatment, and microvascular complication status did not differ
      between the groups. In regression logistic analysis, HbA(1c) was the only
      significant predictor of TWA positivity (odds ratio 5.7, 95% CI 1.3-26, P =
      0.023) after controlling for potential confounders. CONCLUSIONS: These results
      suggest that in Type 2 diabetic patients without clinically manifest CVD, TWA
      positivity is common (approximately 20%) and is closely correlated with glycaemic
      control.

PMID- 16433720
TI  - Insulin allergy in a patient with Type 2 diabetes successfully treated with
      continuous subcutaneous insulin infusion.
AB  - BACKGROUND: Patients with poor control of Type 2 diabetes on maximum oral
      hypoglycaemic therapy invariably need insulin therapy. Insulin allergy is
      uncommon, particularly in patients with Type 2 diabetes. Management of the
      condition can be difficult, and here we report the case of a patient with Type 2
      diabetes and insulin allergy successfully managed with a continuous subcutaneous
      insulin infusion (CSII). CASE REPORT: A 60-year-old man was referred with insulin
      allergy. He had poorly controlled Type 2 diabetes (glycated haemoglobin 10.4%),
      on maximum doses of sulphonylurea and metformin, with osmotic symptoms. He was
      compliant with diet and tablets. His diabetes was complicated by retinopathy,
      nephropathy, coronary heart disease, obstructive sleep apnoea, obesity,
      depression and hypertension. He commenced on twice daily mixed insulin and,
      shortly after, developed pain, itching and erythema at the injection sites. The
      sites became indurated and tender, and he had constitutional symptoms. The
      insulin was changed to other preparations, including short- and long-acting
      analogues, with similar responses. Triple therapy with rosiglitazone was tried,
      with no improvement in control. Skin-prick testing confirmed allergy to insulin
      rather than additives. The patient was reluctant to undergo desensitization. He
      was commenced on an insulin pump in addition to his oral hypoglycaemics, and
      achieved fair control (glycated haemoglobin 8.3%) on 88 units of lispro per day,
      with little or no skin or systemic reaction. CONCLUSION: This is the first case
      report of insulin allergy in Type 2 diabetes being successfully managed by CSII.

PMID- 16433722
TI  - IL-18 gene polymorphism confers susceptibility to the development of anti-GAD65
      antibody in Graves' disease.
AB  - AIMS: This study aimed to investigate whether interleukin-18 (IL-18) gene
      polymorphisms are associated with the development of antibody against the 65-kDa
      isoform of recombinant human glutamic acid decarboxylase (GAD65Ab) in patients
      with Graves' disease. METHODS: A total of 398 unrelated Japanese patients with
      Graves' disease, with and without GAD65Ab, were recruited. Three single
      nucleotide polymorphisms in the IL-18 gene were examined and the polymorphic
      allele and the genotype and haplotype frequencies calculated. RESULTS: The
      frequency of the GG genotype at position -4675 of the IL-18 gene was
      significantly lower in Graves' disease patients with GAD65Ab than those without
      (4% vs. 24%, P = 0.0126). The -4675C allele frequency was significantly greater
      in patients with GAD65Ab than those without (69% vs. 53%, P = 0.0168). The
      homozygous -4675G/-607A/-137G haplotype was less common in Graves' disease
      patients with GAD65Ab than those without (4% vs. 23%, P = 0.0144). CONCLUSIONS:
      These findings in a Japanese population indicate that Graves' disease patients
      carrying the GG genotype at position -4657 of the promoter of the IL-18 gene or a
      gene in linkage disequilibrium with the -4675G/-607A/-137G haplotype have a low
      risk for the development of GAD65Ab in Graves' disease.

PMID- 16433723
TI  - Increased stress protein ORP150 autoantibody production in Type 1 diabetic
      patients.
AB  - AIMS: Various genetic and environmental stresses interfere with protein folding
      in the endoplasmic reticulum (ER), which leads to the induction of ER stress. It
      has recently been reported that ER stress is involved in the development of
      diabetes in diabetic animal models. The aim of this study is to estimate ER
      stress levels in Type 1 diabetic patients. METHODS: We recruited Type 1 diabetic
      patients undergoing periodic follow-up examinations (n = 91) and healthy non
      diabetic individuals (n = 37), and measured their serum anti-oxygen-related
      protein (ORP)150 autoantibody levels. RESULTS: Anti-ORP150 autoantibody levels in
      Type 1 diabetic patients were significantly higher compared with those in healthy
      non-diabetic subjects. Furthermore, the serum autoantibody levels in Type 1
      diabetic patients correlated with HbA(1c) (F > 3.0, P = 0.079), indicating that
      hyperglycaemia itself induces ER stress in diabetes. CONCLUSIONS: Anti-ORP150
      autoantibody levels in Type 1 diabetic patients are higher compared with non
      diabetic subjects, suggesting that ER stress is increased in Type 1 diabetes.

PMID- 16433724
TI  - Repeat education with self-monitoring of blood glucose improves HbA1c.

PMID- 16433726
TI  - Chronic intermittent ethanol exposure during adolescence blocks ethanol-induced
      inhibition of spontaneously active hippocampal pyramidal neurons.
AB  - BACKGROUND: Binge alcohol drinking among adolescents has been a serious public
      health problem. A model of binge alcohol, chronic intermittent ethanol exposure
      (CIEE), during adolescence significantly attenuates ethanol-induced spatial
      memory deficits in rats. However, the attenuation was absent following a 12-day
      ethanol-free period. Since spatial memory is hippocampal dependent, a reduction
      in ethanol-induced spatial memory impairments may be due to a reduction in the
      ability of ethanol to inhibit the firing rate of single hippocampal pyramidal
      neurons following CIEE. METHODS: Beginning on postnatal day 30 (P30), male
      adolescent Sprague-Dawley rats (Harlan) were administered 5.0 g/kg ethanol (n =
      10, CIEE-treated group) or an equivolume saline (n = 10, CISE-treated group)
      every 48 hours for 20 days. Single hippocampal pyramidal neurons from 5 CIEE
      treated rats and 5 CISE-treated rats were recorded on the day following
      completion of the chronic intermittent exposure procedure (animals now P50).
      Additionally, neurons from 5 CIEE-treated rats and 5 CISE-treated rats were
      recorded 12 days after the completion of the chronic intermittent exposure
      procedure (animals now P62). RESULTS: Ethanol exposure during adolescence
      completely blocked ethanol-induced inhibition of hippocampal pyramidal neurons in
      rats that were CIEE exposed. However, the effect of CIEE on hippocampal
      neurophysiology was time dependent. Specifically, neurons recorded from CIEE
      treated rats after a 12-day ethanol-free period had similar maximal inhibition as
      neurons from CISE-treated animals, although the time to reach inhibition was
      significantly greater in neurons from CIEE-treated rats. CONCLUSION: Chronic
      ethanol exposure during adolescence produces a reduction, or tolerance, to
      ethanol-induced inhibition of hippocampal pyramidal neural activity. Although the
      tolerance was greatly reversed after a 12-day ethanol-free period, neurons from
      CIEE animals inhibited slower than neurons from CISE animals. Since the
      hippocampus is known to be involved not only in spatial memory, but also in many
      other types of memory formation, the altered hippocampal functions because of
      CIEE during adolescence should be taken as a serious warning for society.

PMID- 16433727
TI  - Gene by environment interaction: the -159C/T polymorphism in the promoter region
      of the CD14 gene modifies the effect of alcohol consumption on serum IgE levels.
AB  - BACKGROUND: Serum IgE is increased in heavy drinkers. Endotoxin mediates most of
      the immunological alterations associated with heavy drinking. The -159C/T
      polymorphism in the promoter region of the gene encoding CD14 (an endotoxin
      receptor) is associated with serum IgE levels in different populations. AIM: To
      investigate the possible interaction between alcohol intake and the -159C/T
      polymorphism in the promoter region of the CD14 gene for serum IgE levels.
      METHODS: A total of 415 individuals (51.6% males, median age 50 years, range 18
      92 years) were studied. A total of 140 individuals were alcohol abstainers, 112
      were moderate drinkers (1-280 g/week), and 163 were heavy drinkers (>280 g/week).
      Main determinations included the CD14/-159C/T genotype, a panel of skin prick
      tests, total serum IgE, and specific serum IgE against common aeroallergens
      (Phadiatop test). RESULTS: Heavy drinking was associated with increased total
      serum IgE values and with positive specific serum IgE to common aeroallergens,
      but the association was stronger in carriers of the CD14/-159C allele (either CC
      homozygotes or CT heterozygotes) than in CD14/-159TT homozygotes. Both additive
      and multiplicative interactions between heavy drinking and the CD14/-159C allele
      for total and specific serum IgE values was still present after adjusting for
      potential confounders. Neither alcohol consumption nor the CD14/-159 genotype was
      associated with skin prick test positivity. CONCLUSIONS: The CD14/-159C/T
      polymorphism modifies the effect of alcohol consumption on serum IgE levels.

PMID- 16433728
TI  - Analysis of metallothionein brain gene expression in relation to ethanol
      preference in mice using cosegregation and gene knockouts.
AB  - BACKGROUND: Metallothioneins (MTs) are ubiquitously expressed intracellular
      proteins that bind heavy metals and are involved in cytoprotection against
      several types of stress agents including chemicals, hormones, and oxidants. We
      have previously reported 1 isoform, MT-II, as a possible candidate gene for
      ethanol (EtOH) preference (EP) determination in mice. METHODS: Semiquantitative
      RT-PCR was used to determine brain mRNA levels of MT-I and MT-III in 4 inbred
      mouse strains with variable EP. Following this, cosegregation of MT-II brain
      expression with EP was analyzed in F2 mice from 2 intercrosses (C57BL/6J x
      BALB/cJ and C57BL/6J x DBA/2J). Studies on MT-I/MT-II knockout (KO) mice were
      also undertaken to further explore this relationship. RESULTS: Our results
      suggest that MT-I is responsive to EtOH, with no evidence of basal-level
      differences between strains. Conversely, MT-III shows no EtOH response, yet
      indicates a possible strain-specific feature with C57BL/6J having the lowest
      levels of brain MT-III. Metallothionein-II expression cosegregates with EP in F2
      mice from a C57BL/6J (preferring) and DBA/2J (avoiding) intercross. Although F2
      mice from a cross with C57BL/6J and BALB/cJ (avoiding) strains follow a similar
      pattern, the results are not statistically significant. Metallothionein-I/MT-II
      knockout (MT-KO) mice appear to have smaller litter sizes as well as higher
      weight compared with controls (129S1/SvImJ) and also show a slight increase in
      EP. CONCLUSIONS: Metallothionein-II remains the primary candidate of the mouse MT
      gene family for involvement in EP. Its effect on EP appears to be dependent on
      the genetic background. Such conclusions are based on results from C57BL/6J,
      BALB/cJ, DBA/2J, and 129 inbred mouse strains. Evidence also points to shared
      neural pathways involved in weight gain and obesity. The complex interactions
      between MT-II, EP, and weight gain/obesity remain to be studied.

PMID- 16433730
TI  - Prenatal ethanol exposure increases ethanol reinforcement in neonatal rats.
AB  - BACKGROUND: Recent experimental findings indicate that newborn rats are quite
      susceptible to the reinforcing properties of ethanol (EtOH). The basis seems to
      be more pharmacological than gustatory, olfactory, or caloric as a single pairing
      of a surrogate nipple providing water with an intraperitoneal (i.p.) injection of
      EtOH results in conditioned attachment to an empty surrogate nipple. The present
      study tested whether prenatal exposure to moderate EtOH during late gestation
      would alter the neonatal rat's susceptibility to this source of EtOH
      reinforcement and/or EtOH metabolism. METHODS: Pregnant females were given 1 g/kg
      EtOH or water intragastrically on gestational days (GD) 17 to 20 or were
      untreated. Rat pups delivered by cesarean section on GD 21 were exposed 3 to 4
      hours later to a surrogate nipple providing water, either immediately following
      or 10 minutes before an i.p. injection of 0.0 (saline), 0.25, 0.5, or 0.75 g/kg
      EtOH (12.6%, v/v). Ethanol reinforcement was indicated by a significant increase
      in time attached to an empty surrogate nipple compared with unpaired and saline
      controls. Testing was conducted 90 minutes after conditioning took place. Blood
      ethanol levels (BELs) were also taken from subjects injected with identical doses
      of i.p. EtOH at 5 or 95 minutes after injection. RESULTS: Initial response to a
      surrogate nipple with water did not differ between groups. For neonates
      prenatally exposed to EtOH, significant reinforcement by all 3 doses of i.p. EtOH
      (0.25, 0.5, and 0.75) was found, whereas only the dose of 0.5 g/kg EtOH was
      reinforcing for neonates in the prenatal water condition and only 0.25 g/kg was
      reinforcing for pups from untreated dams. Blood ethanol levels after conditioning
      also differed as a function of prenatal treatment. CONCLUSIONS: These results
      suggest that prenatal EtOH exposure increases the range of EtOH doses capable of
      reinforcing effects. Intubations with water, however, eliminated the reinforcing
      strength of the lowest dose (0.25 g/kg) and shifted the dose-response curve to
      the right. This effect may be due to the stress of the intubation procedure.
      Ethanol metabolism was also affected by prenatal EtOH exposure. Pups derived from
      EtOH-treated dams had slower elimination of EtOH from the blood than all other
      groups at both the 0.5 and 0.75 g/kg i.p. doses.

PMID- 16433729
TI  - Validity of transdermal alcohol monitoring: fixed and self-regulated dosing.
AB  - BACKGROUND: To study the validity of transdermal assessment of alcohol
      concentration measured by a lightweight, noninvasive device. METHODS: Subjects
      wore a 227-g anklet that sensed transdermal alcohol concentrations (TACs) every
      15 to 30 minutes, downloading results to a remote computer each day. Twenty-four
      subjects entered a laboratory and received a dose of 0, 0.28, or 0.56 g/kg of
      ethanol. Breath alcohol concentrations (BrAC) and TAC were measured every 15 to
      30 minutes Twenty others [10 alcohol dependent (AD) and 10 not (NAD)] in the
      community who wore the anklet for 8 days kept a drinking log and provided a BrAC
      sample each day. RESULTS: In the laboratory, no zero-dose subject, and every
      subject receiving alcohol, had alcohol-positive TACs. The device distinguished
      low- and high-alcohol-dosing groups using peak (t14 = 3.37; p < 0.01) and area
      under the curve (t14 = 3.42; p < 0.01) of TACs. Within dosing groups, average TAC
      curves were broader (right-shifted) and had lower peaks than average BrAC curves.
      For community participants, self-reported number of drinks (t18 = -3.77; p <
      0.01), area under the TAC curve (t9.5 = -3.56; p < 0.01), and mean TAC (t9.9 = 
      3.35; p < 0.01) all significantly distinguished the AD and NAD groups. However,
      individual transdermal readings were not reliably quantitatively equivalent to
      simultaneously obtained breath results. CONCLUSIONS: Within the limits of the
      laboratory study, the device consistently detected consumption of approximately 2
      standard drinks. On average, the device shows discriminative validity as a
      semiquantitative measure of alcohol consumption but individual readings often are
      not equivalent to simultaneous BrACs.

PMID- 16433732
TI  - Measuring craving: an attempt to connect subjective craving with cue reactivity.
AB  - BACKGROUND: Better insight into craving may contribute to the development of more
      efficient relapse prevention strategies. Inconsistent findings on the relation
      between craving and relapse may be due to difficulties in the measurement of
      craving. These difficulties are accounted for by 3 interrelated problems: lack of
      consensus regarding the definition of craving, the use of different time frames
      (craving now vs craving in the past), and lack of concordance between self
      reported craving and psychophysiological measures of cue reactivity. The aim of
      this study is to develop and validate a new self-report questionnaire for the
      assessment of the core aspects of craving, taking into account different time
      frames and emphasizing the psychophysiological aspects of craving. It is
      hypothesized that this questionnaire will show higher concordance with measures
      of cue reactivity than existing self-report craving questionnaires. METHODS:
      Based on a semantic mapping sentence, a 24-item self-report questionnaire was
      developed: the Jellinek Alcohol Craving Questionnaire (JACQ). The questionnaire
      was tested in 2 samples of treatment-seeking alcohol-dependent patients (sample
      A, n = 251; sample B, n = 48). Psychometric properties were examined in sample A
      and cross-validated in sample B. The associations with psychophysiological and
      neuroendocrine measures of cue reactivity were studied in sample B. RESULTS: The
      JACQ consists of 1 dimension with the following 4 aspects: (1) emotional urge,
      (2) physical sensations, (3) temptation to drink, and (4) uncontrolled thoughts.
      All (sub)scales had a good internal consistency (alpha = 0.77-0.95) and were
      highly intercorrelated (r = 0.57-0.86). Craving-past correlated low with craving
      now (r = 0.32). Craving-now (sub)scales showed a moderate association with heart
      rate (0.46-0.49), but not with respiration rate, skin conductance, or cortisol
      production in saliva following cue exposure. In contrast, craving-past
      (sub)scales showed a moderate association with cortisol production in saliva
      (0.15-0.42) following cue exposure. Remarkably, the physical symptoms scale did
      not show stronger association with psychophysiological and neuroendocrine
      measures than the other subscales. CONCLUSIONS: The JACQ reliably measures 1
      dimension including 4 aspects of craving for distinct time frames. Despite the
      presence of a special subscale for physical sensations, only moderate
      relationships were found between self-reported craving and biological indicators
      of cue reactivity. These findings suggest individual differences between
      alcoholics in the detection and/or reporting of cue-related psychophysiological
      signs as indicators of cue reactivity. Further research should focus on the
      nature of these individual differences. In addition, more research is needed on
      the relative predictive validity of subjective phenotypic indicators of craving
      (such as self-reported craving) versus objective endophenotypic indicators of
      craving (such as physiological measures of cue reactivity) for example in the
      prediction of relapse.

PMID- 16433731
TI  - Effects of chronic alcohol and repeated deprivations on dopamine D1 and D2
      receptor levels in the extended amygdala of inbred alcohol-preferring rats.
AB  - BACKGROUND: Dopaminergic (DA) activity in the extended amygdala (EA) has been
      known to play a pivotal role in mediating drug and alcohol addiction. Alterations
      of DA activity within the EA after chronic exposure to alcohol or substances of
      abuse are considered a major mechanism for the development of alcoholism and
      addiction. To date, it is not clear how different patterns of chronic alcohol
      drinking affect DA receptor levels. Therefore, the current studies investigated
      the effects of chronic ethanol consumption, with or without deprivations, on D1
      and D2 receptor densities within the EA. METHODS: Inbred alcohol-preferring (iP)
      rats were divided into 3 groups with the following treatments: (1) water for 14
      weeks; (2) continuous alcohol (C-Alc) for 14 weeks [24-hour concurrent access to
      15 and 30% (v/v) ethanol]; or (3) repeatedly deprived of alcohol (RD-Alc) (24
      hour concurrent access to 15 and 30% ethanol for 6 weeks, followed by 2 cycles of
      2 weeks of deprivation of and 2 weeks of reexposure to ethanol access). At the
      end of 14 weeks, the rats were killed for autoradiographic labeling of D1 and D2
      receptors. RESULTS: Compared with the water control group, both the C-Alc and the
      RD-Alc groups displayed increases in D1 receptor binding density in the anterior
      region of the Acb core, whereas the RD-Alc group displayed additional increases
      in D1 receptor binding density in anterior regions of the lateral and
      intercalated nuclei of the amygdala. Additionally, both C-Alc and RD-Alc rats
      displayed increases in D2 receptor binding density in anterior regions of the Acb
      shell and core, whereas RD-Alc rats displayed additional increases in D2 receptor
      binding density in the dorsal striatum. CONCLUSION: The results of this study
      indicate that 14-week extended alcohol drinking with continuous chronic or
      repeated deprivations increase binding sites of D1 and D2 receptors in specific
      regions of the EA with greater sensitivity in the anterior regions. The repeated
      deprivation has greater effect on altering D1 and D2 receptor binding sites in
      the Acb, dorsal striatum, and subamygdala regions. The current result indicates
      that the two drinking paradigms may have common as well as differential
      mechanisms on alteration of dopamine receptor-binding sites in specific regions
      of the EA.

PMID- 16433733
TI  - Quality of care for acute myocardial infarction in elderly patients with alcohol
      related diagnoses.
AB  - BACKGROUND: Elderly adults with alcohol-related diagnoses represent a vulnerable
      population that may receive lower quality of treatment during hospitalization for
      acute myocardial infarction. We sought to determine whether elderly patients with
      alcohol-related diagnoses are less likely to receive standard indicators of
      quality care for acute myocardial infarction. METHODS: We conducted a
      retrospective cohort analysis using administrative and medical record data from
      the Cooperative Cardiovascular Project. Subjects were Medicare beneficiaries with
      a confirmed principal discharge diagnosis of acute myocardial infarction from all
      acute care hospitals in the United States over an 8-month period. Our primary
      outcome was the receipt of 7 guideline-recommended care measures among all
      eligible patients and patients who were ideal candidates for a given measure.
      RESULTS: In all, 1,284 (1%) of the 155,026 eligible patients met criteria for an
      alcohol-related diagnosis. Among the alcohol-related diagnoses, 1,077/1,284 (84%)
      were for the diagnoses of alcohol dependence or alcohol abuse. Patients with
      alcohol-related diagnoses were less likely than those without alcohol-related
      diagnoses to receive beta-blockers at the time of discharge (55% vs. 60%, p =
      0.02). We found no other significant differences in performance of the quality
      indicators after stratifying by indication and adjustment for baseline
      characteristics. CONCLUSIONS: Alcohol-related diagnoses are not a barrier to
      receiving most quality of care measures in elderly patients hospitalized for
      acute myocardial infarction.

PMID- 16433734
TI  - Acute ethanol treatment modulates Toll-like receptor-4 association with lipid
      rafts.
AB  - BACKGROUND: Alcohol, a substance that is most frequently abused, suppresses
      innate immune responses to microbial pathogens. The host senses pathogens via
      Toll-like receptors (TLRs). Recent studies indicate that alcohol affects TLR
      signaling. METHODS: Here, we hypothesized that acute alcohol treatment may
      interfere with early steps of membrane-associated TLR2 and TLR4 signaling at the
      level of lipid rafts. Human monocytes and Chinese hamster ovary (CHO) cells,
      transfected with human TLR2, TLR4, or CD14, were stimulated with peptidoglycan
      (PGN, TLR2 ligand) or lipopolysaccharide (LPS, TLR4 ligand) with or without
      alcohol (50 mM) and analyzed for cytokine production (enzyme-linked immunosorbent
      assay), nuclear factor-kappaB (NF-kappaB) activation (electrophoretic mobility
      shift assay), membrane fluidity (fluorescent pyrene eximer formation), and
      partition of cellular membrane into cholesterol-rich, detergent-resistant domains
      (DRMs; Western blot). RESULTS: We determined that both TLR2 and TLR4 were located
      outside the rafts; flotillin, a DRM marker, was resident in the rafts, while CD14
      was equally distributed in and outside the rafts in a steady-state condition. PGN
      forced TLR2 to migrate into DRMs. Engagement of TLR4 and CD14 with LPS induced
      their migration into the rafts. Alcohol prevented TLR4 partitioning; however, it
      did not affect TLR2 migration into the rafts. Furthermore, alcohol downregulated
      TLR4-induced, but not TLR2-induced, NF-kappaB activation and cytokine production
      in monocytes. We found that alcohol increased membrane fluidity and depleted
      cellular cholesterol in CHO cells without affecting cell viability. CONCLUSIONS:
      These data demonstrate for the first time that alcohol disturbs TLR4 and CD14
      association with lipid rafts. We propose that alcohol-induced effects on lipid
      rafts may contribute to modulation of TLR4-CD14-triggered early cellular
      responses.

PMID- 16433735
TI  - Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment:
      impact of alcohol deterrents on outcome.
AB  - OBJECTIVE: (1) To perform a 9-year study of abstinence, lapse, and relapse in 180
      chronic alcoholic patients, participants of the Outpatient Longterm Intensive
      Therapy for Alcoholics (OLITA); (2) To investigate the role of supervised alcohol
      deterrents (AD) in relapse prevention and as an adjunct for maintenance of long
      term abstinence. METHOD: This prospective open treatment study evaluates the long
      term course of drinking outcomes and AD use of 180 chronic alcoholics
      consecutively admitted from 1993 to 2002. Subsamples are compared for (1) sham-AD
      versus verum-AD (disulfiram/calcium carbimide), (2) coped lapses versus finally
      detrimental lapses versus malignant relapses, and (3) AD use for 13 to 20 versus
      >20 months. RESULTS: In this 9-year study, the cumulative probability of not
      having relapsed was 0.52, and that of not having consumed any alcohol was 0.26.
      Despite long-term use, disulfiram/calcium carbimide was well tolerated. Patients
      on sham-AD (due to contraindications to verum-AD) showed higher cumulative
      abstinence probability than patients on verum (S = 0.86 vs. S = 0.49, p = 0.03).
      Detrimental lapses and malignant relapses occurred earlier than successfully
      coped lapses (p < 0.001); patients with detrimental lapse and with malignant
      relapse had fewer days of AD intake and less subsequent days without AD than
      patients with coped lapse (p < 0.001). The cumulative abstinence probability was
      S = 0.75 for patients with long-term intake compared with S = 0.50 for patients
      who stopped AD between months 13 and 20 (p < 0.001). CONCLUSIONS: An abstinence
      rate of >50% in this 9-year study strongly supports the concept of comprehensive,
      long-term outpatient treatment of alcoholics. Supervised, guided intake of AD,
      also over extended periods, can be used as a predominantly psychologically acting
      ingredient of successful alcoholism therapy.

PMID- 16433736
TI  - Alcohol prices, beverage quality, and the demand for alcohol: quality
      substitutions and price elasticities.
AB  - BACKGROUND: Although the published literature on alcohol beverage taxes, prices,
      sales, and related problems treats alcoholic beverages as a simple good, alcohol
      is a complex good composed of different beverage types (i.e., beer, wine, and
      spirits) and quality brands (e.g., high-, medium-, and low-quality beers). As a
      complex good, consumers may make substitutions between purchases of different
      beverage types and brands in response to price increases. For this reason, the
      availability of a broad range of beverage prices provides opportunities for
      consumers to mitigate the effects of average price increases through quality
      substitutions; a change in beverage choice in response to price increases to
      maintain consumption. METHODS: Using Swedish price and sales data provided by
      Systembolaget for the years 1984 through 1994, this study assessed the
      relationships between alcohol beverage prices, beverage quality, and alcohol
      sales. The study examined price effects on alcohol consumption using seemingly
      unrelated regression equations to model the impacts of price increases within 9
      empirically defined quality classes across beverage types. The models enabled
      statistical assessments of both own-price and cross-price effects between types
      and classes. RESULTS: The results of these analyses showed that consumers respond
      to price increases by altering their total consumption and by varying their brand
      choices. Significant reductions in sales were observed in response to price
      increases, but these effects were mitigated by significant substitutions between
      quality classes. CONCLUSIONS: The findings suggest that the net impacts of
      purposeful price policy to reduce consumption will depend on how such policies
      affect the range of prices across beverage brands.

PMID- 16433737
TI  - Hepcidin is down-regulated in alcoholic liver injury: implications for the
      pathogenesis of alcoholic liver disease.
AB  - BACKGROUND: Alcoholic liver disease is known to be associated with abnormal iron
      homeostasis, and iron metabolism itself is regulated by the liver-derived peptide
      hepcidin. Both CCAAT enhancer binding protein alpha (C/EBPalpha) and interleukin
      6 (IL-6) have been shown to regulate hepcidin gene transcription. AIM: To
      investigate mechanisms underlying alcohol-induced disturbances in iron
      homeostasis by measuring the expression of hepcidin and C/EBPalpha mRNA using in
      vivo and in vitro models of alcoholic liver injury. METHODS: Male rats were pair
      fed an alcoholic liquid diet for 12 weeks. RT-PCR was performed on liver tissue
      using specific primers for hepcidin and C/EBPalpha. The effect of alcohol on
      hepcidin and C/EBPalpha gene expression was also determined in isolated
      hepatocytes, HuH-7 cells and HepG2 cells treated with 50 mM ethanol, 200 microM
      acetaldehyde, and/or 20 ng/ml IL-6. RESULTS: Hepcidin and C/EBPalpha mRNA
      expression were significantly decreased in alcohol-fed rats compared with pair
      fed controls (6-fold p < 0.001 and 2.2-fold p < 0.0002 reduction, respectively)
      and hepatic lipid peroxidation was increased by 32.5% (p < 0.05) in alcohol-fed
      rats compared with controls. Hepcidin gene expression was not altered
      significantly in cells cultured in the presence of 50 mM ethanol. Following 24
      hour stimulation by IL-6, there was a 4-fold increase in hepcidin expression in
      hepatocytes and a 9-fold increase in HuH-7 cells. Ethanol (50 mM) attenuated the
      IL-6-induced increase in hepcidin expression in HuH-7 cells (9-fold to a 4-fold
      increase) but not in hepatocytes. Acetaldehyde had no effect on hepcidin gene
      expression in cells in culture. CONCLUSION: The down-regulation of hepcidin and
      C/EBPalpha gene expression shown in vivo implies disturbed iron sensing
      contributing to the hepatosiderosis seen in alcoholic liver disease, possibly by
      mechanisms involving the IL-6 signaling cascade.

PMID- 16433738
TI  - Sedative and GABAergic effects of ethanol on male and female rats.
AB  - BACKGROUND: Women consume less alcohol than men, and yet they are more
      susceptible than men to the negative medical consequences of alcohol use, such as
      cirrhosis of the liver, cardiac disease, and cognitive impairments. This sex
      difference is also reflected in animal studies, in which male and female rats
      differ on both behavioral and electrophysiological measures. Given that one
      significant difference between males and females is the cycling fluctuations of
      the sex hormones, this study aimed to compare the relative sensitivity of
      adolescent and adult rats of both sexes and varying estrous stages to the
      behavioral and electrophysiological effects of ethanol. METHODS: Adult female
      rats were lavaged daily for estrous cycle assessment. Following administration of
      5 g/kg ethanol, adolescent and adult male and female animals were observed for
      loss of the righting reflex. Then, using whole-cell recording, we tested the
      response of spontaneous, gamma-aminobutyric acid (GABA(A)) receptor-mediated
      inhibitory postsynaptic currents (sIPSCs) in hippocampal slices from drug-naive
      adult male and female rats. RESULTS: Consistent with previous findings,
      adolescent animals were less sensitive than adults to the effect of ethanol on
      the righting reflex. In addition, adult proestrous and diestrous female rats were
      less sensitive than male rats to the sedative effects of ethanol. Finally,
      ethanol increased the frequency of sIPSCs in hippocampal pyramidal neurons and
      did so more potently in cells from male rats than in those from female rats.
      CONCLUSIONS: Female animals are less sensitive to the behavioral sedative effects
      of ethanol than adult male rats, and the effect is pronounced in the proestrous
      and diestrous states. This sex difference may be related to differential
      sensitivity of GABA receptor-mediated central nervous system function to ethanol
      in females.

PMID- 16433739
TI  - Developmental differences in the sensitivity of spontaneous and miniature IPSCs
      to ethanol.
AB  - BACKGROUND: Ethanol (EtOH) consumption by juveniles and adolescents is an
      important public health problem. Recent studies have indicated that adolescent
      animals are less sedated by EtOH than adult animals and experience less motor
      impairment. Thus, human adolescents may be able to consume more EtOH prior to
      sedation, putting them at greater risk for EtOH addiction and other negative
      consequences of EtOH use. However, the mechanisms underlying this developmental
      difference are unknown. One contributing factor may be gamma-aminobutyric acid-A
      (GABA(A)) receptor-mediated inhibition, which is known to produce sedation. We
      have shown that evoked, GABA(A) receptor-mediated inhibitory postsynaptic
      currents (IPSCs) are less powerfully enhanced by EtOH in neurons from juvenile or
      adolescent animals than in those from adult animals; however, the mechanisms of
      this developmental difference in sensitivity are unknown. METHODS: Using whole
      cell recording, we tested the response of spontaneous and miniature GABA(A)
      receptor-mediated IPSCs (sIPSCs and mIPSCs) to EtOH in rat hippocampal slices
      from animals representing two distinct developmental stages: adolescent and
      adult. RESULTS: We found significantly greater EtOH-induced enhancement of the
      frequency of sIPSCs in cells from adult animals compared to those from adolescent
      animals. Although EtOH also increased the frequency of mIPSCs, this effect was
      not age dependent. EtOH did not significantly affect the kinetics of mIPSCs.
      CONCLUSIONS: We conclude that the sensitivity of GABA(A) receptor-mediated
      inhibitory processes to EtOH increases with development from the adolescent
      period to adulthood, and that this is likely mediated by developmental changes in
      the effect of EtOH on interneuron excitation.

PMID- 16433741
TI  - Moderate alcohol intake in humans attenuates monocyte inflammatory responses:
      inhibition of nuclear regulatory factor kappa B and induction of interleukin 10.
AB  - BACKGROUND: In contrast to the deleterious effects of chronic excessive alcohol
      consumption on the liver and cardiovascular system, modest alcohol intake, such
      as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is
      known about the length of time or the amounts of alcohol consumed that may cause
      alterations in inflammatory cells such as monocytes that are crucial to
      atherosclerotic vascular disease. Here, we determine in vivo effects of acute
      alcohol consumption on inflammatory cytokine production and nuclear regulatory
      factor kappaB (NF-kappaB) binding in human monocytes. METHODS: Human blood
      monocytes were isolated by plastic adherence before and after acute alcohol
      consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and
      superantigen-induced tumor necrosis factor alpha (TNF alpha), interleukin (IL)
      1beta, and IL-10 production were then determined in monocytes by ELISA. Nuclear
      regulatory factor-kappaB activity of monocytes before and after alcohol
      consumption was estimated by electromobility shift assay and promoter-driven
      reporter activity. IkappaBalpha was determined by Western blotting in the
      cytoplasmic extracts. RESULTS: Eighteen hours after moderate alcohol consumption,
      we found a significant reduction in monocyte production of inflammatory
      mediators, TNF-alpha and IL-1beta, in response to LPS or staphylococcal
      enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA
      binding of the p65/p50 NF-kappaB in monocytes that regulates the expression of
      both the TNF-alpha and the IL-1beta genes. Consistent with this, acute alcohol
      treatment (25 mM) significantly reduced LPS-induced activation of an NF-kappaB
      driven reporter gene suggesting inhibition of this proinflammatory signaling
      pathway. Further, LPS-induced IkappaBalpha degradation was not affected by acute
      alcohol consumption indicating an IkappaBalpha-independent mechanism, as observed
      earlier in the in vitro acute alcohol studies. In contrast, monocyte production
      of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake.
      CONCLUSIONS: Our findings suggest that acute alcohol consumption has dual anti
      inflammatory effects that involve augmentation of IL-10 and attenuation of
      monocyte inflammatory responses involving inhibition of NF-kappaB. These
      mechanisms may contribute to the beneficial effects of moderate alcohol use on
      atherosclerosis.

PMID- 16433740
TI  - Rapid induction of apoptosis in gastrulating mouse embryos by ethanol and its
      prevention by HB-EGF.
AB  - BACKGROUND: Ethanol exposure during gastrulation and early neurulation induces
      apoptosis within certain embryonic cell populations, leading to craniofacial and
      neurological defects. There is currently little information about the initial
      kinetics of ethanol-induced apoptosis, and interest in the ability of endogenous
      survival factors to moderate apoptosis is growing. Ethanol alters intracellular
      signaling, leading to cell death in chick embryos, suggesting that apoptosis
      could occur rapidly and that signaling pathways activated by survival factors
      might reduce apoptosis. METHODS: Pregnant mice were intubated with 1, 2, or 4
      g/kg ethanol on day 7.5 of embryogenesis (E7.5) 1, 3, or 6, hours before
      harvesting gastrulation-stage embryos. Control animals received maltose/dextran.
      Blood alcohol concentrations (BAC) were determined by gas chromatography. E7.5
      embryos isolated from untreated dams were cultured in vitro for 1 or 3 hr with 0
      or 400 mg% ethanol and 0 or 5 nM heparin-binding epidermal growth factor (EGF)
      like growth factor (HB-EGF). Apoptosis was quantified using fluorescence
      microscopy to detect annexin V binding and DNA fragmentation [terminal
      deoxynucleotidyl transferase-mediated dUTP-X nick end labeling (TUNEL)] in whole
      mount or sectioned embryos. RESULTS: Both annexin V binding and TUNEL were
      elevated (p < 0.05) in embryos exposed in utero to 1 g/kg ethanol for 3 hours,
      increasing linearly with time and ethanol concentration. Apoptosis increased (p <
      0.05) in all germ cell layers. Mice treated with 4 g/kg sustained BAC of 400 mg%
      for nearly 3 hours, significantly increasing apoptosis within the first hour.
      Cultured embryos exposed to 400 mg% ethanol displayed 2- to 3-fold more TUNEL
      than vehicle-treated embryos (p < 0.05); however, exogenous HB-EGF prevented
      apoptosis. CONCLUSIONS: Ethanol rapidly produced apoptosis in gastrulation-stage
      embryos, consistent with induction by intracellular signaling. The ethanol
      induced apoptotic pathway was blocked by the endogenous survival factor, HB-EGF.
      Differences in the expression of survival factors within individual embryos could
      be partly responsible for variations in the teratogenic effects of ethanol among
      offspring exposed prenatally.

PMID- 16433742
TI  - Immune reactivity is more suppressed in patients with alcoholic liver disease
      than in patients with virus-induced cirrhosis after CRH stimulation.
AB  - BACKGROUND: The most frequent diagnoses for liver transplantation are virus
      induced cirrhosis (VIC) and alcoholic liver disease (ALD), after an abstinence
      period of at least 6 months. Chronic ethanol consumption has been linked to an
      abnormal neuroendocrine-immune axis and to an altered surgical stress response
      inducing an increased infection rate. Preoperative stress testing might be
      relevant to detect stress-induced immune alteration. The aim of this study was to
      investigate the preoperative stress-like response to corticotrophin-releasing
      hormone challenge (CRH) of patients with ALD compared with patients with VIC and
      their immune sequelae. METHODS: Nine patients with ALD and 8 patients with VIC
      were included in this clinical study prior to transplantation. All patients
      received CRH in the morning. Blood samples were drawn before and after stress
      testing. RESULTS: In response to CRH, the ALD patients showed a significant
      decrease in the plasma interleukin (IL)-6/IL-10 ratio. After lipopolysaccharide
      stimulation of whole blood from CRH-challenged ALD patients, IL-10 increased
      significantly. The cytotoxic T1-(Tc1) to cytotoxic T2 (Tc2) ratio was
      significantly decreased in ALD patients after the stress test. Infections
      occurred significantly more often in ALD patients within the past year before
      study inclusion. CONCLUSIONS: ALD patients showed a stronger anti-inflammatory
      immune status and response than VIC patients. This difference was associated with
      a higher infection rate despite a median alcohol abstinence time of 3.5 years.
      Although an altered immune response is well known among patients with actual
      alcohol-use disorders, to the best of our knowledge, it is not described in
      patients after such a long abstinence time.

PMID- 16433743
TI  - Dispersion of the corrected QT and JT interval in the electrocardiogram of
      alcoholic patients.
AB  - BACKGROUND: The aim of this study was to analyze the corrected QT interval (QTc),
      its dispersion (QTcd), and the QT interval index (QTcI) and to compare it with
      the corrected JT interval (JTc), its dispersion (JTcd), and the JT interval index
      (JTcI) in long-term alcoholic users, by investigating the ventricular activation
      until the completion of repolarization. METHODS: The study of ECGs was performed
      on a selected group of 49 male white alcoholic patients, mean age 53.51+/-4.78
      years. The control group was pair-matched. The analysis of ECGs was performed
      according to the Minnesota Code, and Bazett's formula gave the values of the
      corrected QT interval and JT interval. RESULTS: The results of the descriptive
      statistics in the group of alcoholics showed a range of the QTcd of 12.0 to 103.0
      milliseconds, mean 44.2+/-18.6 milliseconds, compared with 5.0 to 68.0
      milliseconds, mean 23.8+/-11.1 milliseconds, in the control group (p < 0.0001).
      The range of JTcd in the alcoholic patients was 11.0 to 88.0 milliseconds, mean
      43.0+/-18.3 milliseconds, compared with 5.0 to 66.0 milliseconds, mean 22.8+/
      12.1 milliseconds, in the control group (p < 0.0001). The QTc from 422.0 to 480.0
      milliseconds was obtained in 69.4% of the alcoholic patients and 32.6% of the
      controls. The QTc over 480.0 milliseconds was found in 24.5% of the alcoholic
      patients, but was not recorded among the controls at all (p < 0.0001). The QTcd
      over 50.0 milliseconds was registered in 34.7% of the alcoholic patients, while
      in the controls a QTcd above 50 milliseconds was found in 2.0% (p < 0.0001). The
      mean values of QT were markedly higher in the alcoholic patients (p < 0.01) than
      in the controls. The same was the case with the values of QTd, QT(I), QTcd, and
      QTcI (p < 0.0001). Also, the mean values of JTd, JT(I), JTc, JTcd, and JTcI were
      significantly higher in the alcoholic patients than in the controls (p < 0.0001).
      The mean value of JT, although higher in the alcoholic patients, did not
      significantly differ between the examined groups (p=0.1002). The odds ratio
      estimated for prolonged QTc and for enlarged QTcd in the alcoholics versus the
      controls was 31.625 and 25.500 (p < 0.0001), respectively. CONCLUSIONS: Persons
      who consume various alcoholic beverages excessively and for a long time have
      significantly higher dispersions of the QTc and JTc, intervals and they have a
      significantly higher estimation of relative risk for the prolonged QTc interval
      and higher QTc dispersion than the control group, i.e., higher risk of
      arrhythmias.

PMID- 16433744
TI  - The alcohol clamp: applications, challenges, and new directions--an RSA 2004
      symposium summary.
AB  - This article summarizes the proceedings of a symposium organized and cochaired by
      Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on
      Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium
      were: (1) to provide a rationale for the development and use of the alcohol clamp
      and the requirements for its use in alcohol challenge studies; (2) to highlight
      recent studies conducted using the alcohol clamp to identify sources of variation
      in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address
      important research questions related to the relationship between the response to
      alcohol and the risk for alcoholism; and (3) to provide a perspective on
      progress, address limitations of the clamp, and identify new directions for
      alcohol challenge research. The symposium began with an introduction and overview
      of the alcohol clamp, by Vijay Ramchandani. This was followed by 4 presentations
      that highlighted recent studies conducted using the clamp including: (1)
      determination of the influence of alcohol dehydrogenase polymorphisms on alcohol
      elimination rates in a male Jewish population, by Yehuda Neumark; (2) examination
      of family history of alcoholism, recent drinking history, and levels and rates of
      administration as determinants of the response to alcohol and risk for
      alcoholism, by Sean O'Connor; (3) evaluation of the time course of ethanol
      intoxication on neuroendocrine function in humans, by Ulrich Zimmermann; and (4)
      a study of the effects of steady-state blood alcohol levels on auditory event
      related potentials in rats, by Sandra Morzorati. Harriet de Wit summarized and
      discussed the research presented at the symposium and provided her perspective on
      future directions for research using the alcohol clamp.

PMID- 16433746
TI  - Organ exchanges: fairness to the O-blood group.

PMID- 16433747
TI  - Mortality after kidney transplantation: what lessons can we learn from regional
      and country variation?

PMID- 16433748
TI  - Finding a home for cell transplants: location, location, location.

PMID- 16433749
TI  - Retransplantation after polyomavirus-associated nephropathy: just do it?

PMID- 16433750
TI  - Lies, damn lies, and statistics: the perils of the P value.

PMID- 16433751
TI  - Antifibrotic agents for liver disease.
AB  - Complications from chronic hepatitis C (HCV) and recurrent HCV post-transplant
      are responsible for significant morbidity and mortality in the United States and
      Europe. Current antiviral therapies are at best, effective in up to 50% of
      patients in the pre-transplant setting, and in the post-transplant setting are
      associated with more limited efficacy and increased toxicity. With this reduced
      efficacy of antiviral strategies in the post-transplant setting, new approaches
      are urgently needed. Substantial progress has been made in understanding the
      pathogenesis of hepatic fibrosis over the last 20 years, which has yielded
      potential new therapeutic targets. The prospect of antifibrotic therapies is
      nearing reality in order to reduce progression to cirrhosis, thereby reducing
      morbidity, mortality and the need for re-transplantation. Current and evolving
      approaches primarily target the activated hepatic stellate cells, which are the
      main source of extracellular matrix, along with related fibrogenic cell types.
      Key issues yet to be clarified include the optimal duration of antifibrotic
      therapies, endpoints of clinical trials, indications in clinical practice and
      whether combination therapies might yield synergistic activity.

PMID- 16433752
TI  - Laryngeal transplantation in 2005: a review.
AB  - There is no good surgical, medical or prosthetic solution to the problems faced
      by those with a larynx whose function is irreversibly damaged by tumor or trauma.
      Over the past 10 years, the pace of research designed to establish laryngeal
      transplantation as a therapeutic option for these persons has increased steadily.
      The biggest milestone in this field was the world's first true laryngeal
      transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues
      to function well, in many respects, even after 7 years. However, it has also
      highlighted the remaining barriers to full-scale clinical trials. Stimulated by
      these observations, several groups have accumulated data which point to answers
      to some of the outstanding questions surrounding functional reinnervation and
      immunomodulation. This review seeks to outline the progress achieved in this
      field by 2005 and to point the way forward for laryngeal transplantation research
      in the 21st century.

PMID- 16433753
TI  - LFA-1 (CD11a) as a therapeutic target.
AB  - Leukocyte function associated antigen-1 (LFA-1) was one of the earliest of cell
      surface molecules identified by monoclonal antibodies generated against leukocyte
      immunogens. This integrin heterodimer is perhaps best known as a classic adhesion
      molecule facilitating the interaction between T cells and antigen-presenting
      cells. However, varied studies indicate that LFA-1 has multi-faceted roles in the
      immune response including adhesion, activation and trafficking of leukocyte
      populations. While there has been long-standing interest in LFA-1 as a
      therapeutic target for regulating immunity, anti-LFA-1 therapy is still not a
      first-line indication for any clinical condition. Antagonism of LFA-1 with
      monoclonal antibodies, either alone or in combination with other agents, can
      result in regulatory tolerance in vivo. Furthermore, new generation humanized
      anti-LFA-1 monoclonal antibodies (Efalizumab) show at least modest promise for
      continued application in clinical trials. Thus, anti-LFA-1 forms a potential, but
      still largely unexploited, immunotherapy which may find its greatest application
      as an agent which augments other therapies.

PMID- 16433754
TI  - Direction of the Organ Procurement and Transplantation Network and United Network
      for Organ Sharing regarding the oversight of live donor transplantation and
      solicitation for organs.
AB  - The Organ Procurement and Transplantation Network (OPTN) operated by United
      Network for Organ Sharing (UNOS) has taken recent steps to address public
      solicitation for organ donors and its oversight of live donor transplantation.
      This report provides the direction of the OPTN regarding deceased donor
      solicitation. The OPTN has authority under federal law to equitably allocate
      deceased donor organs within a single national network based upon medical
      criteria, not upon one's social or economic ability to utilize resources not
      available to all on the waiting list. The OPTN makes a distinction between
      solicitations for a live donor organ versus solicitations for directed donation
      of deceased organs. As to live donor solicitation, the OPTN cannot regulate or
      restrict ways relationships are developed in our society, nor does it seek to do
      so. OPTN members have a responsibility of helping protect potential recipients
      from hazards that can arise from public appeals for live donor organs. Oversight
      and support of the OPTN for live donor transplantation is now detailed by
      improving the reporting of live donor follow-up, by providing a mechanism for
      facilitating anonymous live kidney donation, and by providing information for
      potential live kidney donors via the UNOS Transplant Living website.

PMID- 16433755
TI  - Antioxidant supplementation enhances erythrocyte antioxidant status and
      attenuates cyclosporine-induced vascular dysfunction.
AB  - The aim of this study was to determine the effects of dietary antioxidant
      supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine
      induced alterations to erythrocyte and plasma redox balance, and cyclosporine
      induced endothelial and smooth muscle dysfunction. Rats were randomly assigned to
      either control, antioxidant, cyclosporine or cyclosporine + antioxidant
      treatments. Cyclosporine A was administered for 10 days after an 8-week feeding
      period. Plasma was analyzed for alpha-tocopherol, total antioxidant capacity,
      malondialdehyde and creatinine. Erythrocytes were analyzed for glutathione,
      methemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6
      phosphate dehydrogenase, alpha-tocopherol and malondialdehye. Vascular
      endothelial and smooth muscle function was determined in vitro. Antioxidant
      supplementation resulted in significant increases in erythrocyte alpha-tocopherol
      concentration and glutathione peroxidase activity in both of the antioxidant
      supplemented groups. Cyclosporine administration caused significant decreases in
      glutathione concentration, methemoglobin concentration and superoxide dismutase
      activity. Antioxidant supplementation attenuated the cyclosporine-induced
      decrease in superoxide dismutase activity. Cyclosporine therapy impaired both
      endothelium-independent and -dependent relaxation of the thoracic aorta, and this
      was attenuated by antioxidant supplementation. In summary, dietary
      supplementation with alpha-tocopherol and alpha-lipoic acid attenuated the
      cyclosporine-induced decrease in erythrocyte superoxide dismutase activity and
      attenuated cyclosporine-induced vascular dysfunction.

PMID- 16433756
TI  - In vivo engineering of metabolically active hepatic tissues in a neovascularized
      subcutaneous cavity.
AB  - Recent success in clinical hepatocyte transplantation therapy has encouraged
      further investigation into bioengineering hepatic tissues in vivo. Engineering
      tissues in the subcutaneous space is an attractive method; however, hepatocyte
      survival has been transient due to insufficient vascular network formation. To
      establish a vascularized cavity, we created a polyethylene terephthalate mesh
      device coated with poly(vinylalcohol) that allowed for the gradual release of
      basic fibroblast growth factor (bFGF), a potent angiogenic factor. The efficacy
      of the bFGF-releasing device in inducing vascular network formation in the
      subcutaneous space was observed in mouse and rat studies. Isolated mouse
      hepatocytes transplanted into newly vascularized subcutaneous cavities allowed
      for persistent survival up to 120 days. In the absence of a vascularized
      compartment, the survival of the transplanted hepatocytes was markedly
      diminished. Functional maintenance of the engineered hepatic tissues was
      confirmed by high expression of liver-specific mRNAs and proteins. These
      engineered hepatic tissues have the ability to take up inoculated compounds and
      express strong induction of drug-metabolizing enzymes, demonstrating functional
      relevance as a metabolic tissue. In conclusion, we have created a novel
      technology to engineer functionally active hepatic tissues in the subcutaneous
      space, which will likely facilitate hepatocyte-based therapies.

PMID- 16433757
TI  - Liver ischemia contributes to early islet failure following intraportal
      transplantation: benefits of liver ischemic-preconditioning.
AB  - Early graft failure following intraportal islet transplantation (IPIT) represents
      a major obstacle for successful islet transplantation. Here, we examined the role
      of islet emboli in the induction of early graft failure and utilized a strategy
      of ischemic-preconditioning (IP) to prevent early islet destruction in a model of
      syngeneic IPIT in STZ-induced diabetic mice. Numerous focal areas of liver
      necrosis associated with the islet emboli were observed within 24 h post-IPIT.
      Pro-inflammatory cytokines, IL-1beta and IL-6, were significantly increased 3 h
      after IPIT, while TNF-alpha was elevated for up to 5 days post-IPIT. Caspase-3
      and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      positive cells were observed in the transplanted islets trapped in areas of
      necrotic liver at 3 h and 1 day post-IPIT. Hyperglycemia was corrected
      immediately following IPIT of 200 islets, but recurrence of hyperglycemia was
      observed within 14 days associated with a poor response to glucose challenge. IP,
      a procedure of pre-exposure of the liver to transient ischemia and reperfusion,
      protected the liver from embolism-induced ischemic injury and prevented early
      islet graft failure. These data suggest that islet embolism in the portal vein is
      a major cause of functional loss following IPIT that can be prevented by liver
      IP.

PMID- 16433758
TI  - Concurrent antiviral and immunosuppressive activities of leflunomide in vivo.
AB  - We previously reported that the immunosuppressive malononitrileamides leflunomide
      and FK778 exert antiviral activity against cytomegalovirus (CMV). In the current
      investigation, we tested the hypothesis that leflunomide exerts concurrent
      antiviral activity and immune suppression in CMV-infected cardiac allograft
      recipients. Lewis rats were transplanted with Brown Norway hearts and then
      inoculated with rat CMV. Plaque assay demonstrated that leflunomide (30
      mg/kg/day) reduced viral loads by 4-6 logs, and that the reduction in viral load
      was unaffected by administration of uridine. Leflunomide was as effective as
      cyclosporine A (CsA) or tacrolimus in preservation of allograft integrity through
      day 28. These studies directly demonstrate the bifunctionality of leflunomide as
      concurrently immunosuppressive and antiviral, enhancing the promise of this agent
      as a clinical option for treatment of transplant recipients.

PMID- 16433760
TI  - Attitudes of minority patients with end-stage renal disease regarding ABO
      incompatible list-paired exchanges.
AB  - A few transplant centers in the United States have implemented list-paired
      exchange programs that include both ABO-compatible and ABO-incompatible living
      donor recipients. ABO-incompatible list-paired exchanges raise ethical concerns
      because they increase the total number of organs available but increase the
      waiting time for wait-list candidates of blood type O. In this manuscript, we
      explore attitudes of a convenience sample of minority patients with end-stage
      renal disease (ESRD) regarding living paired exchanges, ABO-compatible and ABO
      incompatible list-paired exchanges and ABO-incompatible direct transplants. Data
      from 87 minority respondents were analyzed. Eighty-seven (100%) supported living
      paired exchanges and ABO-compatible list-paired exchanges. In contrast, only 50
      of 85 (59%) respondents supported ABO-incompatible list-paired exchanges (p <
      0.001), including half (12 of 24) of those with blood type O. Subjects were asked
      how much additional time it would be fair to ask wait-list candidates of blood
      type O to wait to implement ABO-incompatible list-paired exchanges. Forty percent
      (35 of 87) responded 'no additional time' and another 10% (9 of 87) responded
      'one month or shorter'. Minority dialysis patients hold mixed opinions about the
      fairness of ABO-incompatible list-paired exchanges. If our findings are confirmed
      in a more diverse randomly selected sample, then the UNOS variances that permit
      these exchanges should be reconsidered.

PMID- 16433759
TI  - Regulation of ILT3 gene expression by processing of precursor transcripts in
      human endothelial cells.
AB  - Immunoglobulin-like transcript (ILT)-3 is a transmembrane receptor, which belongs
      to the immunoglobulin superfamily. In previous studies, we showed that
      allospecific CD8+CD28- T suppressor cells (Ts) induce the expression of ILT3 in
      human endothelial cells (EC) rendering them tolerogenic. Using a polymerase chain
      reaction (PCR)-based approach, we now demonstrate by cell fractionation and
      sequencing studies that ILT3 precursor RNA is expressed and retained in nuclei of
      resting EC. Ts interaction with EC or exposure of EC to interleukin-10 (IL-10)
      and interferon alpha (IFN-alpha) triggers processing of ILT3 pre-mRNA. Western
      blot analysis showed that the expression of the mature ILT3 transcript is
      accompanied by production of ILT3 protein.

PMID- 16433761
TI  - Chronic kidney disease following non-myeloablative hematopoietic cell
      transplantation.
AB  - Chronic kidney disease (CKD) following myeloablative allogeneic hematopoietic
      cell transplantation (HCT) occurs in 20% of survivors at 1 year and is believed
      to be due to radiation nephritis. Non-myeloablative allogeneic HCT is a recent
      procedure that employs significantly lower doses of chemoradiotherapy, however,
      incidence and risk factors for CKD following non-myleoablative HCT have not been
      defined. We performed a retrospective cohort study of 122 patients from three
      institutions who were available for analysis at 6 months following non
      myeloablative HCT. Patients received two Gy of radiation; 62% received
      fludarabine as preconditioning. CKD was defined as at least a 25% reduction in
      glomerular filtration rate (GFR) from baseline using the abbreviated modified
      diet in renal disease (MDRD) equation. Eighty-one of 122 patients (66%) showed
      evidence of CKD at follow-up. Multivariate analysis revealed that acute renal
      failure (ARF) during the first 100 days post-transplant was associated with
      development of CKD (Adjusted OR 32.8 with 95% CI 4.3-250) after controlling for
      other variables. Previous autologous HCT, long-term calcineurin inhibitor use and
      extensive chronic GVHD were independently associated with CKD. CKD following non
      myeloablative HCT appears to be a distinct clinical entity and likely not related
      to radiation nephritis. Future research should focus on possible mechanisms for
      alleviating chronic injury and decreasing use of calcineurin inhibitors.

PMID- 16433762
TI  - Risk factors and long-term outcome of transplant renal artery stenosis in adult
      recipients after treatment by percutaneous transluminal angioplasty.
AB  - Transplant renal artery stenosis (TRAS) is a common complication of kidney
      transplantation but attempts to identify predisposing risk factors for TRAS have
      yielded conflicting results. In order to determine the predisposing factors for
      transplant (TRAS), we retrospectively reviewed the records of 29 renal allograft
      recipients with TRAS treated with percutaneous transluminal angioplasty (PTA).
      The TRAS group was compared with a case-control group of 58 patients.
      Predisposing factors for TRAS included CMV infection (41.4% vs. 12.1% p = 0.0018)
      and initial delayed graft function (DGF) (48.3% vs. 15.5% p = 0.0018),
      respectively in the TRAS and the control group. Acute rejection occurred more
      frequently in patients from the TRAS group (48.3%) compared with the control
      group (27.6%), although the difference was not significant (p = 0.06). In a
      multivariate analysis, only CMV infection (p = 0.005) and DGF (p = 0.009) appear
      to be significantly and independently associated with TRAS. The long-term graft
      survival was significantly higher in the control group, compared with the TRAS
      group (p = 0.03). Our study suggests that CMV infection and DGF are two reliable
      risk factors for TRAS. Despite treatment by PTA with primary successful results,
      TRAS significantly affects long-term graft outcome.

PMID- 16433764
TI  - Mortality after kidney transplantation: a comparison between the United States
      and Canada.
AB  - There is a paucity of comparative studies on country-specific outcomes in kidney
      transplantation. We compared post-transplant mortality among primary, adult,
      solitary kidney transplant recipients (KTR) from the United States (n = 70 708)
      and Canada (n = 5773), between January 1, 1991 and December 31, 1998, using data
      from the Scientific Registry of Transplant Recipients and the Canadian Organ
      Replacement Register. Multivariable Cox regression revealed higher adjusted post
      transplant mortality among U.S. (vs. Canadian) KTR (HR = 1.35 [95% CI 1.24, 1.47;
      p < 0.005]). Mortality risk in the first post-transplant year was similar in both
      countries but higher in the United States beyond the first year (HR = 1.49-1.53;
      p < 0.005). There was no difference in mortality among patients transplanted
      within 1 year of starting dialysis, but mortality was increased in U.S. (vs.
      Canadian) patients after 1-2 and 4+ years on dialysis (HR = 1.36-1.66; p <
      0.005). Greater mortality was also seen in U.S. patients with diabetes mellitus
      and/or graft failure. In conclusion, there are considerable differences in the
      survival of KTR in the United States and Canada. A detailed examination of
      factors contributing to this variation may yield important insights into
      improving outcomes for all KTR.

PMID- 16433763
TI  - Assessing glomerular filtration rate by estimation equations in kidney transplant
      recipients.
AB  - Surveillance of glomerular filtration rate (GFR) is crucial in the management of
      kidney transplant recipients. With special emphasis on serum creatinine (SCr)
      calibration assay, we assessed the performance of estimation equations as
      compared to iothalamate GFR (iGFR) in 209 patients using the modification of diet
      in renal disease (MDRD), Nankivell and Cockcroft-Gault methods. Fifty-five
      percent of patients were treated with a calcineurin inhibitor (CNI) and all were
      taken trimethroprim-sulfametoxazole at the time of SCr measurement. The mean iGFR
      was 44 +/- 26 mL/min/1.73 m2. The MDRD equation showed a median difference of 0.9
      mL/min/1.73 m2 with 53% of estimated GFR within 20% of iGFR. Median differences
      were 7.5 and 7.0 mL/min/1.73 m2 for Nankivell and Cockcroft-Gault formulas,
      respectively. The accuracy of the Nankivell and Cockcroft-Gault formulas was such
      that only 38% and 37% of estimations, respectively, fell within 20% of iGFR. The
      performance of all equations was not uniform throughout the whole range of GFR,
      with some deterioration at the extremes of GFR levels. In addition, good
      performance of the MDRD equation was seen in subjects taking CNI. In conclusion,
      the overall performance of the MDRD equation was superior to the Nankivell and
      Cockcroft-Gault formulas in renal transplant recipients including subjects
      treated with CNI.

PMID- 16433765
TI  - Altruistic living donors: evaluation for nondirected kidney or liver donation.
AB  - A program was established within our regional procurement organization to permit
      evaluation of altruistic living donors (LD) interested in nondirected kidney or
      liver segment donation prior to transplant center referral. During the initial 30
      months of program operations, 731 donor inquiries were received of which 131
      individuals called back after review of mailed information materials. Forty-seven
      candidates initiated and 19 completed the evaluation process. Seven underwent
      donation to include six kidneys and one liver segment, five are actively pending
      donation, five were excluded from donation following transplant center evaluation
      and two took no further action after their intended liver recipients received
      deceased donor (DD) transplants. Psychological evaluation of these 19 candidates
      found them to be free of psychopathology, highly cooperative and self-directed.
      They did not exhibit attention-seeking or religious motivations for their
      actions. All seven donors and recipients continue to do well postoperatively.
      This evaluation program has made possible large-scale screening and education of
      prospective altruistic LD within the general population and also provides a
      unique opportunity to further our understanding of those individuals interested
      in living-nondirected donation.

PMID- 16433766
TI  - Mycophenolic acid 12-h trough level monitoring in renal transplantation:
      association with acute rejection and toxicity.
AB  - Studies of renal transplantation utilizing trough plasma level monitoring of
      mycophenolic acid (MPA) have shown inconsistent associations with toxicity and
      rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant
      recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a
      steroid sparing protocol (steroids for 7 days only) were sequentially analyzed.
      Higher MPA levels were associated with lower hemoglobin concentrations and anemia
      (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower
      total white cell counts and an increased incidence of leucopenia (total white
      cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also
      associated with hemotoxicity. MMF-associated diarrhea and viral infection were
      associated with higher MPA levels. Conversely, biopsy-proven acute rejection
      within the first month post-transplantation was associated with lower MPA levels.
      Anti-CD25 antibody induction was also associated with reduced rejection rates. No
      association was seen between MPA levels and platelet count, thrombocytopenia or
      bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best
      discriminated patients with and without rejection, and an MPA level of 2.75 mg/L
      best discriminated patients with and without toxicity later post-transplantation.

PMID- 16433767
TI  - The incidence and costs of sepsis and pneumonia before and after renal
      transplantation in the United States.
AB  - We compared the graft survival and accumulative costs associated with sepsis and
      pneumonia pre- and post-transplantation. We analyzed 44 916 first kidney
      transplants from 1995 to 2001 USRDS where Medicare was the primary payer. We drew
      five cohorts for each disease from the baseline population: patients who had a
      disease onset in the first or second years pre-transplantation (cohorts 1 and 2)
      or post-transplantation (cohorts 3 and 4) and patients who were disease-free
      (cohort 5). For each cohort, we calculated graft survival and average accumulated
      Medicare payments (AAMPs) for the two pre- and post-transplantation years. Graft
      survival: new-onset sepsis and pneumonia both significantly (p <0.01) lowered
      graft survival during the year of onset. AAMPs: the AAMPs incurred by sepsis-
      (pneumonia-) free patients during the first and second years post-transplantation
      were dollar 50,000 and 13,000 (dollar 51,100 and 13,500), respectively. Patients
      with a sepsis (pneumonia) onset post-transplantation cost on average dollar
      48,400 (dollar 38,400) extra (p<0.01). Episodes of sepsis and pneumonia have a
      strong and independent impact on graft survival and costs.

PMID- 16433768
TI  - Refractory ascites after liver transplantation: an analysis of 1058 liver
      transplant patients at a single center.
AB  - A retrospective study of 1058 liver transplant recipients was performed to
      determine: (i) the incidence, etiology, timing, clinical features and treatment
      of refractory ascites (RA), (ii) risk factors for RA development, (iii)
      predictors of RA disappearance, (iv) predictors of survival following RA and (v)
      the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and
      its disappearance occurred in 27/62 cases. Patients having hepatitis C virus
      (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No
      other baseline characteristic was associated with RA. Cox stepwise regression
      analysis of the hazard rate of RA disappearance found two significant factors:
      HCV recurrence as the reason for developing RA implied a poorer outcome (p =
      0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In
      addition, survival following RA was significantly poorer among patients having
      bacterial peritonitis or HCV recurrence. Finally, the mortality rate was
      significantly (nearly 8.6 times) higher in patients following RA development
      while it was ongoing (p < 0.00001); however, if the RA disappeared, then the
      additional risk of death also disappeared. This study illustrates the importance
      of developing an optimal treatment strategy to (i) effectively treat RA if it
      develops and (ii) prevent hepatitis C recurrence.

PMID- 16433769
TI  - Noninvasive discrimination of rejection in cardiac allograft recipients using
      gene expression profiling.
AB  - Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and
      variable. We investigated gene expression profiling of peripheral blood
      mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence)
      from moderate/severe rejection (ISHLT > or = 3A). Patients were followed
      prospectively with blood sampling at post-transplant visits. Biopsies were graded
      by ISHLT criteria locally and by three independent pathologists blinded to
      clinical data. Known alloimmune pathways and leukocyte microarrays identified 252
      candidate genes for which real-time PCR assays were developed. An 11 gene real
      time PCR test was derived from a training set (n = 145 samples, 107 patients)
      using linear discriminant analysis (LDA), converted into a score (0-40), and
      validated prospectively in an independent set (n = 63 samples, 63 patients). The
      test distinguished biopsy-defined moderate/severe rejection from quiescence (p =
      0.0018) in the validation set, and had agreement of 84% (95% CI 66% C94%) with
      grade ISHLT > or = 3A rejection. Patients >1 year post-transplant with scores
      below 30 (approximately 68% of the study population) are very unlikely to have
      grade > or = 3A rejection (NPV = 99.6%). Gene expression testing can detect
      absence of moderate/severe rejection, thus avoiding biopsy in certain clinical
      settings. Additional clinical experience is needed to establish the role of
      molecular testing for clinical event prediction and immunosuppression management.

PMID- 16433770
TI  - Impaired left ventricular systolic function early after heart transplantation is
      associated with cardiac allograft vasculopathy.
AB  - Cardiac allograft vasculopathy (CAV) is a major cause of death more than 1 year
      after heart transplantation. We evaluated the role and possible predictive value
      of different etiological factors on development of CAV as diagnosed by
      quantitative coronary angiography (QCA). A total of 121 patients were studied
      with baseline QCA and 117 had a follow-up study at 1 year to assess the
      relationship of mean lumen diameter loss (MLDL) in main coronary arteries to
      immunological and non-immunological factors potentially affecting long-term
      survival. Out of them, 103 patients were males (85%), 114 (94%) patients were
      Caucasians and mean age was 48.5 +/- 10 years. Univariate analysis showed that
      MLDL at 1 year was inversely related to echocardiographic fractional shortening
      (FS) measured within the first week after transplantation (p = 0.0098) and to
      intracranial hemorrhage as cause of donor death (p = 0.04) and was directly
      related to male donors (p = 0.0008), domino transplants (p = 0.037) and donor
      negative cytomegalovirus (CMV) status (p = 0.022). Multivariate analysis showed
      that initial FS (p = 0.006) and donor intracranial hemorrhage as a cause of death
      (p = 0.042) were inversely related to MLDL whereas donor male sex (p = 0.003) and
      prednisolone treatment throughout the first year (p = 0.012) were directly
      related. Thus, left ventricular systolic dysfunction early after heart
      transplantation was associated with subsequent development of CAV.

PMID- 16433771
TI  - Everolimus versus azathioprine in maintenance lung transplant recipients: an
      international, randomized, double-blind clinical trial.
AB  - Everolimus is a proliferation signal inhibitor with immunosuppressive activity
      that may reduce the rate of progression of chronic rejection, bronchiolitis
      obliterans syndrome (BOS), after lung transplantation. In a randomized, double
      blind clinical trial, 213 BOS-free maintenance patients received everolimus (3
      mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and
      corticosteroids. The prospectively defined primary endpoint was the incidence of
      efficacy failure (decline in FEV1 >15%[deltaFEV1 >15%], graft loss, death or loss
      to follow-up) at 12 months. Incidence of efficacy failure at 12 months was
      significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p =
      0.046); at 24 months, rates of efficacy failure became similar between the
      groups. At 12 months, the everolimus group had significantly reduced incidences
      of deltaFEV1 >15%, deltaFEV1 >15% with BOS, and acute rejection. At 24 months,
      only incidence of acute rejection remained significantly less in the everolimus
      group. Treatment discontinuations (particularly due to adverse events), serious
      adverse events and high serum creatinine values were more common with everolimus.
      For the first time, a drug has demonstrated significant slowing of loss in lung
      function, suggesting that patients kept on prolonged maintenance treatment with
      everolimus may benefit from replacing AZA with everolimus 3 months after lung
      transplantation.

PMID- 16433772
TI  - Donor-to-host transmission of bacterial and fungal infections in lung
      transplantation.
AB  - The purpose of this study was to evaluate the incidence and etiology of bacterial
      and fungal infection or contamination in lung allograft donors and to assess
      donor-to-host transmission of these infections. Recipients who survived more than
      24 h and their respective donors were evaluated. The overall incidence of donor
      infection was 52% (103 out of 197 donors). Types of donor infection included
      isolated contamination of preservation fluids (n = 30, 29.1%), graft colonization
      (n = 65, 63.1%) and bacteremia (n = 8, 7.8%). Donor-to-host transmission of
      bacterial or fungal infection occurred in 15 lung allograft recipients, 7.6% of
      lung transplants performed. Among these cases, 2 were due to donor bacteremia and
      13 to colonization of the graft. Twenty-five percent of donors with bacteremia
      and 14.1% of colonized grafts were responsible for transmitting infection.
      Excluding the five cases without an effective prophylactic regimen, prophylaxis
      failure occurred in 11 out of 197 procedures (5.58%). Donor-to-host transmission
      of infection is a frequent event after lung transplantation. Fatal consequences
      can be avoided with an appropriate prophylactic antibiotic regimen that must be
      modified according to the microorganisms isolated from cultures of samples
      obtained from donors, grafts, preservation fluids and recipients.

PMID- 16433773
TI  - Impact of lung transplant operation on bronchiolitis obliterans syndrome in
      patients with chronic obstructive pulmonary disease.
AB  - Previous studies suggest that bilateral (BLT) compared with single lung
      transplantation (SLT) for patients with chronic obstructive pulmonary disease
      (COPD) results in improved long-term survival. The effect of transplant operation
      on bronchiolitis obliterans syndrome (BOS) is unknown. A retrospective study of
      all lung transplant recipients with pre-transplant diagnoses of COPD at the
      University of Toronto and at Duke University was performed. Data collected were
      age, gender, date and type of transplant, acute rejection, survival, presence and
      time of BOS. 221 (bilateral n = 101, single n = 120) patients met our criteria.
      Patients with BLT were younger (53.0 vs. 55.3 years; p = 0.034), more likely to
      be male (56.3% vs. 42.4%; p = 0.039) and more likely to be transplanted at the
      University of Toronto (79.6% vs. 16.1%; p < 0.001). Freedom from BOS was similar
      at 1 year post-transplant. However, BLT recipients were more commonly free from
      BOS 3 years (57.4% vs. 50.7%) and 5 years (44.5% vs. 17.9%) post-transplant (p =
      0.024). Survival of BLT was better than SLT recipients at 3 and 5 years post
      transplant (BLT vs. SLT: 67.5% vs. 61.1% and 60.7% vs. 34.1%, respectively; p =
      0.018). Similar trends on survival were observed after development of BOS. BLT
      results in lower rates of BOS in patients with COPD that are eligible for both
      SLT and BLT.

PMID- 16433775
TI  - Financial analysis of potential donor management at a medicare-approved
      transplant hospital.
AB  - The purpose of this study was to perform a financial analysis of severe brain
      injured (SBI) patient management to determine potential reimbursement versus net
      losses in relation to organ donation and transplantation at a transplant center.
      We undertook a retrospective analysis of financial records of medically suitable
      referrals to the organ procurement organization (OPO) from our institution for
      fiscal years 2002-2003. This included (1) hospital cost and reimbursement, (2)
      OPO reimbursement for actual donors, (3) financial returns on local transplant
      activity solely supported by local donor activity and (4) Medicare incentives for
      local organ donation. There were 48 potential and 18 organ donors for this
      period. The consent rate reduced from 50% to 25% if family was offered withdrawal
      of care. After reimbursements from OPO, Medicare incentives and kidney transplant
      activity solely supported by local organ donation were figured in, the total
      returns were 244% of total cost of SBI patient management. Aggressive proactive
      management of severely brain injured patients remains a good medical practice.
      For Medicare-approved transplant centers, there are additional financial
      incentives to aggressively treat these patients and pursue organ donation.
      Prematurely offering withdrawal of care negatively impacts on the organ donation
      process and hurts institutions financially.

PMID- 16433774
TI  - Organ donation decision: comparison of donor and nondonor families.
AB  - Family members continue to play a prominent role in donation decisions at time of
      death. This study examined the relative influence of donor and next-of-kin
      factors, requestor characteristics, communication processes and satisfaction with
      the health care team on the donation decision. Data were gathered via structured
      telephone interview with 285 next-of-kin of donor-eligible deceased individuals
      who had been approached by coordinators from one organ procurement organization
      (OPO) in the southeastern USA from July 2001 to February 2004. Univariate and
      multivariate analyses showed that several variables were associated with the
      donation decision. Subsequent logistic regression analyses revealed that donation
      was more likely when the deceased was younger, white (OR = 3.20, CI = 1.3, 5.7)
      and had made his/her donation intentions known (OR = 4.35, CI = 2.6, 7.3), and
      when the next-of-kin had more favorable organ donation beliefs (OR = 8.72, CI =
      5.2, 14.7), was approached about donation by an OPO coordinator (OR = 3.74, CI =
      2.2, 6.4), viewed the requestor as sensitive to their needs (OR = 2.70, CI = 1.6,
      4.5) and perceived the timing of the request as optimal (OR = 6.63, CI = 3.6,
      12.1) (total regression model, chi square = 133.2, p < 0.001, 92.7% of cases
      correctly predicted). Findings highlight the need for continued public education
      efforts to maximize positive beliefs about organ donation, to share and document
      donation decisions and to improve communication processes among the OPO
      personnel, hospital staff and prospective donor families.

PMID- 16433777
TI  - Preemptive retransplantation for BK virus nephropathy: successful outcome despite
      active viremia.
AB  - BK virus nephropathy (BKVN) is now recognized as a major cause of renal allograft
      loss. Recent reports suggest that retransplantation in patients with graft loss
      due to BKVN is safe after return to dialysis. Since early transplantation is
      associated with improved outcomes, it would be advantageous if this procedure
      could be performed prior to ultimate graft loss. However, little data are
      available regarding the safety of this approach during active viremia. In this
      report, we describe successful preemptive retransplantation with simultaneous
      allograft nephrectomy in two patients with active BKVN and viremia at the time of
      surgery. With 21- and 12-month follow-up, respectively, both patients have stable
      allograft function and no evidence for active viral replication. We conclude that
      preemptive retransplantation can be considered in patients with failing
      allografts due to BKVN.

PMID- 16433776
TI  - Ezetimibe for the treatment of uncontrolled hypercholesterolemia in patients with
      high-dose statin therapy after renal transplantation.
AB  - We investigated prospectively the efficacy of ezetimibe in addition to statin
      therapy in stable renal transplant patients in whom hypercholesterolemia was not
      sufficiently treated. Eighteen renal transplant patients received 10 mg ezetimibe
      once daily in addition to high-dose statin therapy for uncontrolled
      hypercholesterolemia. Total cholesterol, LDL-cholesterol, HDL-cholesterol,
      triglycerides, Tacrolimus (Tac)- and Cyclosporine A (CsA) blood levels,
      creatinine, urea, liver enzymes, electrolytes and creatinkinase (CK) were
      measured before initiation of ezetimibe therapy, after 7 days, 6 weeks and 3
      months. Cholesterol concentrations decreased significantly (p < 0.005) from 264
      +/- 46 mg/dL at baseline to 205 +/- 48 mg/dL after 1 week to 202 +/- 48 mg/dL
      after 6 weeks and 212 +/- 40 mg/dL after 3 months (reduction after 3 months 21 +/
      10%). LDL-concentrations decreased significantly (p < 0.005) from 178 +/- 41
      mg/dL at baseline to 129 +/- 35 mg/dL after 1 week to 123 +/- 25 after 6 weeks
      and to 117 +/- 40 mg/dL after 3 months (reduction after 3 months 37 +/- 14%). Two
      patients stopped ezetimibe therapy due to nausea and muscle pain without CK
      elevation. Significant changes of CsA and Tac blood levels, liver and muscle
      enzymes were not observed. Ezetimibe seems to be an effective therapy for
      uncontrolled hypercholesterolemia in renal transplant patients when combined with
      high-dose statin therapy.

PMID- 16433778
TI  - Intrapyloric injection of botulinum toxin a for the treatment of persistent
      gastroparesis following successful pancreas transplantation.
AB  - Intrapyloric injection of botulinum toxin A (BoTx) successfully improved symptoms
      in idiopathic and diabetic gastroparesis (DGP) refractory to medical treatment.
      Therefore, we used it in three pancreas transplant patients done in our
      institution during the last 18 months. They had severe, persistent DGP despite
      successful pancreas transplantation. They received 100 units of BoTx during the
      first injection. The clinical effect became evident within 2 weeks after the
      treatment, and lasted for an average of 29 weeks (range 14-44 weeks). The
      patients' subjective evaluation showed improvement of their symptoms and quality
      of life following BoTx. Patients 2 and 3 had recurrent symptoms at 44 and 24
      weeks, respectively, after the first injection; they required a second dose of 90
      and 80 units, respectively. They are doing well at 3 months follow-up.
      Intrapyloric injection of BoTx is safe and efficient. It should be considered for
      treating residual DGP following successful pancreas transplantation.

PMID- 16433779
TI  - Bilateral hematogenous Pseudomonas aeruginosa endophthalmitis after lung
      transplantation.
AB  - Pseudomonas aeruginosa commonly colonizes the airways of patients with cystic
      fibrosis (CF). However, the occurrence of bacteremia with metastatic infection to
      the eye causing endogenous endophthalmitis is very rare. In the setting of lung
      transplantation, the significance of P. aeruginosa bacteremia in patients with CF
      whose airways are colonized before transplantation is unknown. We report a case
      of bilateral P. aeruginosa endogenous endophthalmitis in a patient with CF after
      lung transplant without documented bacteremia. The patient presented with acute
      eye symptoms in the presence of a left atrial thrombus and the disease followed a
      rapidly progressive course requiring aggressive medical-surgical treatment.
      Typically P. aeruginosa endophthalmitis has been associated with a poor visual
      prognosis. However, with combined medical-surgical management this patient
      retained useful vision in one eye without having retinal detachment or requiring
      enucleation. Endogenous endophthalmitis should be considered in the differential
      diagnosis of ocular complaints in patients with CF after lung transplant.

PMID- 16433780
TI  - A cluster of parvovirus B19 infections in renal transplant recipients: a
      prospective case series and review of the literature.
AB  - Up to 9% of renal transplant recipients have severe multifactorial erythropoietin
      resistant anemia. Human parvovirus B19 (PVB19) infection can cause severe anemia
      and is likely underreported. Sparse information on epidemiology and management in
      this population exists. To address these issues, after our first index case, we
      modified our clinical practice to prospectively screen patients with persistent
      hemoglobin (Hb) <10 mg/dL for PVB19 infection after excluding common causes of
      anemia including erythropoietin resistance. Potentially infected patients were
      further evaluated by serology, qualitative polymerase chain reaction (quPCR) and
      bone marrow biopsy (BMB) for cytomegalovirus, Epstein-Barr virus, PVB19 and other
      etiologies. Over 3 months, 212 kidney recipients visited outpatient clinics. Of
      52 recipients with anemia, 8 had an Hb <10 mg/dL with erythropoietin resistance
      and were screened for PVB19 infection. Three cases had PVB19 infection by quPCR
      and often-inconclusive serology/BMB results. Cases had immunosuppression reduced
      and received IVIG (0.5 gm/kg x 4 doses) with recovery from anemia, viral
      clearance in two cases and one recurrence. PVB19-mediated anemia occurred in up
      to three out of eight (38%) screened kidney recipients with Hb <10 mg/dL
      resistant to erythrypoietin. We recommend prospective risk stratification for
      this population, high indices of suspicion using at least qualitative techniques
      for diagnosis and treatment goal for viral eradication.

PMID- 16433781
TI  - Parenchymal transection of the kidney inflicted by endocatch bag entrapment
      during a laparoscopic donor nephrectomy.
AB  - We present a case of inadvertent decapsulation and grade IV renal parenchyma
      laceration during laparoscopic donor nephrectomy. The kidney was repaired, used
      and functioned immediately. There were no complications in the donor. To our
      knowledge, this type of injury has not been reported previously and the purpose
      of this report is to focus attention on the potential for this unusual injury,
      which can occur during delivery of the kidney using the endocatch bag.

PMID- 16433782
TI  - Anastomotic ulceration following small bowel transplantation.
AB  - We describe, for the first time, anastomotic ulcers (AU) following bowel
      transplantation at the Hospital for Sick Children. Two children presented with
      rectal bleeding, 6 and 9 months, following the transplantation. Isolated ulcers
      were identified at the ileo-colonic and the colo-colonic anastomosis site. The
      ulcers resolved, but recurred 6 and 7 months after the initial presentation. Both
      patients were positive for adenovirus in the stool and were treated with
      rapamycin. The histology revealed granulation tissue formation with mild
      inflammation in the adjacent mucosa, without evidence of rejection or infection.
      A literature search revealed 10 studies reporting 29 patients who developed AU
      following various surgical etiologies, none of which was bowel transplant.
      Numerous factors that are unique to the post-transplant period may predispose to
      such ulcer and are discussed in detail. Physicians and surgeons should be aware
      of this multifactorial complication, among other etiologies, as a cause of anemia
      or rectal bleeding following intestinal transplantation.

PMID- 16433784
TI  - High-risk skin cancer as a contraindication to organ transplant: maximizing the
      likelihood of transplant.

PMID- 16433786
TI  - Atopic dermatitis and cancer risk.
AB  - BACKGROUND: Epidemiological studies have provided growing evidence of a link
      between atopy and cancer risk. OBJECTIVES: To review the evidence from case
      control studies and cohort studies on a possible association between atopic
      dermatitis (AD) and cancer risk, with particular attention to the case definition
      of AD. METHODS: Studies with quantitative data on the association between AD
      (eczematous disease) and cancer risk were obtained from MEDLINE in combination
      with a review of cited references. RESULTS: In 23 publications, AD was implicated
      in the risk of haematological [childhood leukaemia (n = 3), adult leukaemia (n =
      3), non-Hodgkin lymphoma (NHL; n = 4) and different haematological cancers (n =
      1)], pancreatic (n = 5), skin (n = 2) and brain malignancies (n = 5). The overall
      picture of the results of these studies shows that a history of AD may be
      associated with a decreased risk of pancreatic cancer, brain tumour and childhood
      leukaemia, although in most instances the findings were not statistically
      significant. No consistent associations were observed for skin cancer or NHL. The
      definition of AD had varying quality, and was imprecise in the majority of
      publications. CONCLUSIONS: The findings of the epidemiological studies tend to
      support a lower risk of cancer among persons with a history of AD. Although a
      more careful definition of AD is needed, these epidemiological studies could
      provide an estimate of the background cancer risk in patients with AD when the
      long-term effects of treatments for AD are assessed.

PMID- 16433787
TI  - Effects of monomethylfumarate on dendritic cell differentiation.
AB  - BACKGROUND: Fumaric acid esters (FAE) are effective against psoriasis vulgaris
      and monomethylfumarate (MMF) is believed to be the most bioactive metabolite of
      this medication. Earlier we found that the beneficial effects of FAE medication
      are accompanied by a downregulation of type 1 cytokine production by T-helper
      (Th) lymphocytes, which are important as they maintain a type 1 cytokine
      [interferon (IFN)-gamma, interleukin (IL)-2] environment in the skin lesions of
      psoriasis vulgaris patients and once maximal beneficial effects are obtained type
      2 cytokine production is also decreased. In vitro MMF selectively induced type 2
      cytokine production by primed Th lymphocytes, whereas type 1 cytokine production
      by and profileration of T lymphocytes were unaffected. OBJECTIVES: As dendritic
      cells (DCs) present in these skin lesions play a key role in the activation of Th
      lymphocytes, we investigated the effects of MMF on monocyte-derived DC
      differentiation. METHODS: Monocytes were differentiated into immature (i) DCs by
      cytokines with or without MMF. To establish whether these cells were
      differentiated into iDCs, we analysed the expression of cell surface molecules on
      these cells and the capacity to capture antigens using flow cytometry. Next, we
      determined whether these MMF-incubated (MMF-)iDCs could be matured by
      lipopolysaccharide (LPS) and whether MMF affected this responsiveness as well.
      For this purpose we measured cytokine production by these LPS-stimulated cells
      (MMF-DCs) using enzyme-linked immunosorbent assays as well as their ability to
      activate naive Th lymphocytes. RESULTS: The presence of MMF during the
      differentiation of monocytes into iDCs resulted in cells that retained low levels
      of CD14 and hardly expressed CD1a. Upon maturation, these MMF-iDCs upregulated
      CD83 and costimulatory molecules and HLA-DR on their surface, indicating that
      these cells respond to LPS, albeit less than control iDCs. In addition, in
      response to LPS, MMF-iDCs did not decrease the capacity to capture antigens when
      compared with control iDCs. MMF-DCs hardly produced IL-12p70 and IL-10 and low
      levels of tumour necrosis factor (TNF)-alpha, whereas IL-8 produced by MMF-DCs
      and control DCs did not differ. Moreover, MMF-DCs were less able to induce IFN
      gamma production by naive Th lymphocytes compared with control DCs. The
      production of IL-4 and IL-10 by naive Th lymphocytes cocultured with MMF-DCs did
      not differ from that by T cells cocultured with control DCs. CONCLUSIONS: MMF
      inhibited the monocyte-derived DC differentiation resulting in cells that cannot
      be appropriately matured to DCs. Consequently, these MMF-DCs are less effective
      than control DCs in stimulating type 1 cytokine, but not type 2 cytokine
      production, in Th lymphocytes. This general immunomodulatory effect may in part
      explain the beneficial effects of FAE therapy in psoriasis.

PMID- 16433788
TI  - Expression of extracellular matrix protein 1 (ECM1) in human skin is decreased by
      age and increased upon ultraviolet exposure.
AB  - BACKGROUND: The extracellular matrix protein 1 (ECM1) is expressed in human skin
      and plays an important role in its normal structure and function. In the rare
      genetic skin disease lipoid proteinosis, which is characterized by a loss-of
      function mutation in the ECM1 gene, skin areas habitually exposed to the sun may
      show a more severely scarred and photoaged appearance. However, no data are
      available on the possible involvement of ECM1 expression in intrinsic and
      extrinsic skin ageing. OBJECTIVES: We hypothesized that ECM1 expression in human
      skin is regulated by age- and ultraviolet (UV)-dependent mechanisms. METHODS:
      Skin biopsies from 12 patients with histologically confirmed solar elastosis,
      from non-UV-exposed sites of 12 age-matched controls and 12 young subjects were
      analysed. To evaluate the influence of acute UV exposure, buttock skin of 10
      healthy subjects was irradiated repetitively on 10 days with a solar simulator
      and compared intraindividually with non-UV-treated contralateral sites. The
      expression of ECM1 was investigated by immunohistochemistry using an ECM1
      antibody detecting ECM1a and ECM1c isoforms. Semiquantitative analysis of
      staining intensity was carried out by densitometric image analysis. RESULTS: In
      normal human skin ECM1a and ECM1c are expressed mainly in the basal cell layers
      of epidermal keratinocytes and in dermal vessels. For the first time, an
      expression in the outer root sheath of hair follicles, in sebaceous lobules and
      epithelium of sweat glands is described. Intrinsically (UV-protected) aged skin
      shows a significantly reduced expression in basal and upper epidermal cell layers
      compared with young skin. In photoaged skin, expression is significantly
      increased within the lower and upper epidermis compared with age-matched UV
      protected sites. Importantly, after acute UV exposure in young healthy subjects
      expression of ECM1 is markedly increased in both lower and upper epidermal cell
      layers. CONCLUSIONS: This is the first study to demonstrate a regulation of ECM1
      expression in human skin by age and UV exposure. These data suggest that ECM1
      expression may represent a cutaneous stress response to acute and chronic UV
      irradiation.

PMID- 16433789
TI  - Modulation of lymphocyte phenotype and function by immunoglobulins.
AB  - BACKGROUND: Immunoglobulins have immune-modulating capacities and are used for
      the treatment of different dermatological diseases. They have also been reported
      for the treatment of severe atopic dermatitis (AD). OBJECTIVES: To determine the
      effects of immunoglobulins on the phenotype and function of peripheral T and B
      lymphocytes from patients with AD in comparison with healthy donors (HD) as
      controls. METHODS: We studied lymphocyte activation and T-cell cytokine
      production from 12 patients with AD and 10 HD by multicolour flow cytometric
      analysis in the presence of immunoglobulins. RESULTS: Immunoglobulins
      significantly inhibited T-cell activation (CD69), by 71% (AD) and by 62% (HD).
      Production of interferon-gamma and interleukin-4 was also significantly
      inhibited, by 44%/24% (AD) and 38%/10% (HD), respectively. In addition, CD86
      expression on B lymphocytes was downregulated by 30% in AD and by 29% in HD,
      whereas CD23 expression was decreased without reaching statistical significance.
      CONCLUSIONS: Our data demonstrate that, in vitro, immunoglobulins modulate the
      activation and cytokine production of peripheral blood lymphocytes from both HD
      and patients with AD.

PMID- 16433790
TI  - Transfection of CD40 in a human oral squamous cell carcinoma keratinocyte line
      upregulates immune potency and costimulatory molecules.
AB  - BACKGROUND: There is upregulation of class II molecules of the major
      histocompatibility complex (MHC) by keratinocytes in oral squamous cell carcinoma
      (OSCC) and inflammatory diseases such as lichen planus. The significance of this
      expression, or whether it is accompanied by upregulation of membrane-bound
      costimulatory molecules, is unknown. OBJECTIVES: To compare the expression of
      CD40, CD80, CD86, MHC class II and intercellular adhesion molecule-1 (ICAM-1),
      and the ability to induce allogeneic T-lymphocyte proliferation in vitro, of a
      CD40- OSCC cell line, its CD40+ transfected derivative and null transfectants.
      METHODS: OSCC cell lines and purified T lymphocytes were cocultured and T cell
      proliferation recorded. Phenotypes were analysed by flow cytometry. RESULTS:
      After T lymphocyte proliferation, which all OSCC cell lines were able to induce,
      there was upregulation of MHC class II and ICAM-1. However, the CD40+
      transfectants were the most immunologically potent and were the only cells to
      show increased expression of CD86 (as well as further upregulation of CD40 and a
      statistically insignificant rise in CD80). The effects of blocking antibodies on
      T-cell proliferation were only statistically significant with the CD40+
      transfectants. CONCLUSIONS: While not essential, expression of CD40 by OSCC cells
      is necessary for optimal induction of allogeneic T lymphocytes, possibly because
      of concurrent upregulation of other membrane-bound costimulatory molecules.

PMID- 16433791
TI  - Impetigo: incidence and treatment in Dutch general practice in 1987 and 2001-
      results from two national surveys.
AB  - BACKGROUND: Impetigo is a common skin infection in children. The epidemiology is
      relatively unknown, and the choice of treatment is subject to debate. OBJECTIVE:
      The objective of our study was to determine the incidence and treatment of
      impetigo in Dutch general practice, and to assess trends between 1987 and 2001.
      METHODS: We used data from the first (1987) and second (2001) Dutch national
      surveys of general practice. All diagnoses, prescriptions and referrals were
      registered by the participating general practitioners (GPs), 161 and 195,
      respectively. RESULTS: The incidence rate of impetigo increased from 16.5 (1987)
      to 20.6 (2001) per 1000 person years under 18 years old (P < 0.01). In both
      years, the incidence was significantly higher in summer, in rural areas and in
      the southern region of the Netherlands, compared with winter, urban areas and
      northern region, respectively. Socioeconomic status was not associated with the
      incidence rate. From 1987 to 2001, there was a trend towards treatment with a
      topical antibiotic (from 43% to 64%), especially fusidic acid cream and mupirocin
      cream. Treatment with oral antibiotics (from 31% to 14%) and antiseptics (from
      11% to 3%) was prescribed less often. CONCLUSIONS: We have shown an increased
      incidence of impetigo in the past decade, which may be the result of an increased
      tendency to seek help, or increased antibiotic resistance and virulence of
      Staphylococcus aureus. Further microbiological research on the marked regional
      difference in incidence may contribute to understanding the factors that
      determine the spread of impetigo. Trends in prescribing for impetigo generally
      follow evidence-based knowledge on the effectiveness of different therapies,
      rather than the national practice guideline.

PMID- 16433792
TI  - Dermoscopic findings of haemosiderotic and aneurysmal dermatofibroma: report of
      six patients.
AB  - BACKGROUND: The clinical diagnosis of dermatofibroma is commonly easy. However,
      the differentiation of dermatofibroma from other cutaneous tumours is difficult
      in some instances, primarily in atypical cases and rare variants. Haemosiderotic
      dermatofibroma is a variant composed of numerous small vessels, extravasated
      erythrocytes and intra- and extracellular haemosiderin deposits. Aneurysmal
      dermatofibroma is a variant composed of large, blood-filled spaces without
      endothelial lining. Some authors consider that haemosiderotic dermatofibroma is
      an early stage in the development of aneurysmal dermatofibroma. The clinical
      differential diagnosis of haemosiderotic or aneurysmal dermatofibroma must
      include melanoma and other melanocytic tumours, vascular neoplasms, adnexal
      tumours and nonspecific cysts. Dermoscopy improves the diagnostic accuracy in
      pigmented and nonpigmented skin lesions. OBJECTIVES: To evaluate specific
      dermoscopic criteria. METHODS: Dermoscopic examination (using the DermLite Foto;
      3Gen, LLC, Dana Point, CA, U.S.A.) of six patients with haemosiderotic or
      aneurysmal dermatofibromas was performed to evaluate specific dermoscopic
      criteria. RESULTS: A multicomponent pattern with a central bluish or reddish
      homogeneous area in combination with white structures and a peripheral delicate
      pigment network along with vascular structures was noted in five of six lesions.
      CONCLUSIONS: This dermoscopic pattern yielded the diagnosis of haemosiderotic or
      aneurysmal dermatofibroma in most cases. However, this multicomponent pattern may
      present in some melanomas and although it is useful in determining a clinical
      diagnosis of aneurysmal dermatofibroma, it may not be specific to this entity.

PMID- 16433793
TI  - Livedoid vasculopathy: long-term follow-up results following hyperbaric oxygen
      therapy.
AB  - BACKGROUND: Livedoid vasculopathy, also known as atrophie blanche, is a recurrent
      painful vasculopathy appearing mostly on the lower limbs. Treatment is
      challenging and relapses are frequent. OBJECTIVES: To analyse the long-term
      effect and safety of hyperbaric oxygen (HBO) therapy in treating livedoid
      vasculopathy. METHODS: Twelve patients with active livedoid vasculopathy were
      included in this study. All patients underwent HBO therapy five times a week.
      Each week photographs were taken and the total dose of analgesics was recorded.
      Side-effects were documented and assessed. Recurrence was defined as the presence
      of skin ulceration. RESULTS: Of the eight patients who completed the treatment,
      resumption of ambulation and reduction of analgesics were achieved at an average
      of 4.9 HBO therapy sessions. Leg ulcers in all eight patients healed completely
      at a mean of 3.4 weeks (range 2-5 weeks). Six patients suffered relapses of
      ulceration and responded to additional HBO therapy. No significant side-effects
      were found. CONCLUSIONS: HBO is a relatively safe, fast and effective method to
      treat patients with livedoid vasculopathy.

PMID- 16433794
TI  - Familial aggregation of aspirin-induced urticaria and leukotriene C synthase
      allelic variant.
AB  - BACKGROUND: We have reported that in patients with chronic idiopathic urticaria
      (CIU) who reacted adversely to aspirin, the frequency of the (-444)C allele of
      the leukotriene C(4) synthase gene (LTC4S) was higher than in patients who
      tolerated aspirin well. OBJECTIVES: To study the pattern of aspirin-induced
      urticaria (AIU) in two families, with special interest on the polymorphisms of
      LTC4S (AA, AC, CC) and the glutathione S-transferase M1 and P1 genes (GSTM1 and
      GSTP1). METHODS: Of 74 patients with CIU and a history of aspirin
      hypersensitivity studied by us, two patients (probands) gave a family history of
      aspirin intolerance. Oral challenge tests with aspirin were carried out in
      members of these families. Genomic DNA samples were obtained from peripheral
      blood to study the polymorphisms of LTC4S, GSTM1 and GSTP1. RESULTS: In family 1
      the aspirin challenge test confirmed AIU in three of five (60%) individuals, but
      in family 2 only in two of seven (29%). In both families, the variant genotypes
      of LTC4S (AC or CC) were present in the parents, but only one of them had CIU. In
      family 1, with both parents healthy, the three children had AIU; in two it was
      associated with variant LTC4S genotype. In family 2, urticaria following aspirin
      ingestion was present only with variant LTC4S genotype. In patients of both
      families with positive aspirin challenge test, deletion of the GSTM1 gene was
      present. CONCLUSIONS: AIU aggregates in families inheriting the LTC4S(-444)C
      allele. Segregation of aspirin sensitivity in these families does not follow a
      clear Mendelian pattern. A common deletion of GSTM1, one of several enzymes
      involved in conjugation of a wide range of electrophilic substances with
      glutathione, was present in all individuals ascertained to have AIU.

PMID- 16433795
TI  - HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA
      DQA1 locus can be a potential melanoma risk factor.
AB  - BACKGROUND: The association of melanoma with HLA class II loci is under extensive
      debate. Different investigators have found discrepant results due to, at least in
      part, sample size, patient series heterogeneity, choice of control population and
      differences in the techniques employed for the detection of HLA antigens and
      alleles. OBJECTIVES: This study was designed to analyse the possible association
      of melanoma with HLA class II loci with regard to different clinic pathological
      factors and to investigate other risk factors for melanoma susceptibility, such
      as HLA homozygosity. PATIENTS AND METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping
      was performed for 117 eastern Spanish patients presenting with primary melanoma.
      RESULTS: Although there were no significant alterations in the phenotypic
      frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when
      compared with controls, patients exhibited a statistically significant increase
      in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was
      particularly dependent on some features in melanoma patients such as light hair
      colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or
      abscence of atypical naevus syndrome phenotype (aetiological fractions about 10
      20%). Analysis of homozygosity for single DQA1 alleles showed an increased
      homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These
      DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white
      populations, and DQB1*0301 homozygous individuals were significantly increased in
      red in or fair-haired patients (relative risk 5.65). CONCLUSIONS: Our results
      indicate that the contribution of HLA class II alleles to primary melanoma
      incidence is not significant in the Spanish population. However, homozygosity for
      the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be
      considered a potential risk factor for developing melanoma depending on the
      person's genetic background and, perhaps, on certain environmental conditions.

PMID- 16433796
TI  - Oral retinoid therapy for disorders of keratinization: single-centre
      retrospective 25 years' experience on 23 patients.
AB  - BACKGROUND: Over the last three decades, the oral retinoids etretinate and
      acitretin have revolutionized the treatment of disorders of keratinization (DOK).
      Many patients with DOK require life-long treatment with oral retinoids. However,
      the longest follow-up data of patients with DOK on oral retinoid therapy is 10
      years for adults and up to 11 years for children. OBJECTIVES: The aim of our
      study was to collect long-term retrospective data including disease response,
      side-effects and pregnancy outcome in a cohort of patients with DOK who were
      among the first in the world to commence oral retinoids 25 years ago. METHODS:
      Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in
      our department. Case notes of these patients were reviewed retrospectively, and
      patients interviewed where possible to obtain the following information:
      diagnosis, age when treatment commenced, duration of treatment, reason for
      discontinuation of therapy, side-effects, abnormal investigation results and
      pregnancy outcomes. RESULTS: Case notes of 23 of the 30 patients were available
      for review; of these, two patients were deceased and 14 were interviewed. In the
      23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61)
      and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14
      years). Reasons for discontinuing treatment were an overall improvement in the
      skin disease (six of 23), no benefit +/- side-effects (11 of 23) and
      noncompliance (one of 23). Two patients died of causes unrelated to their skin
      disease or treatment, 12 and 4 years after stopping etretinate. Five patients
      (one female, four males) subsequently changed to acitretin and are currently
      continuing therapy. The mean total duration of retinoid therapy (etretinate and
      acitretin) for the four males was 23.7 years (range 20.6-25.1). The female
      patient continued intermittent courses (due to planned pregnancies) of oral
      retinoids for a total of 10.1 years over the last 25 years. Abnormal
      investigation results included elevated serum triglycerides and cholesterol (two
      of 23), isolated high triglycerides (three of 23), isolated high cholesterol
      (three of 23), worsening of liver enzymes in a patient with alcohol dependence,
      and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In
      two children, the elevated pretreatment ALP levels increased further after
      commencing etretinate but returned to normal in adulthood while treatment
      continued. One patient developed diffuse idiopathic skeletal hyperostosis after
      21 years of retinoid therapy. One female patient had two early spontaneous
      abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had
      two normal children. Two other females had normal children 1, 3 and 5 years after
      stopping etretinate. Two male patients fathered a total of three healthy children
      while on etretinate. CONCLUSIONS: This study provides the longest available
      follow-up data of children and adults with DOK on oral retinoid therapy. Such
      information is essential for clinicians and their patients with DOK embarking on
      life-long treatment with retinoids.

PMID- 16433797
TI  - Cutaneous Rosai-Dorfman disease: clinicopathological profiles, spectrum and
      evolution of 21 lesions in six patients.
AB  - BACKGROUND: An uncommon histiocytosis primarily involving the lymph nodes, Rosai
      Dorfman disease (RDD, originally called sinus histiocytosis with massive
      lymphadenopathy) involves extranodal sites in 43% of cases; cutaneous RDD (C-RDD)
      is a rare form of RDD limited to the skin. The clinicopathological diagnosis of C
      RDD may sometimes be difficult, with different clinical profiles from those of
      its nodal counterpart, and occasionally misleading histological pictures. There
      have been few multipatient studies of C-RDD and documentation of its histological
      spectrum is rare. OBJECTIVES: To identify the clinical and histopathological
      profiles, associated features, and the chronological changes of this rare
      histiocytosis. METHODS: From 1991 to 2002, patients diagnosed as having C-RDD
      were collected in four academic hospitals. Clinical presentations, treatments,
      and courses of each case were documented. In total, 21 biopsy specimens obtained
      from these patients were re-evaluated and scored microscopically with attention
      to the uncommon patterns and chronological evolution both clinically and
      histologically. RESULTS: We examined six patients with C-RDD, three men and three
      women. The mean age at the first visit was 43.7 years. The clinical presentations
      were mostly papules, nodules and plaques, varying with the duration and depth of
      lesions. Although the anatomical distribution was wide, the face was most
      commonly involved. Evolutional changes were identified clinically, as the lesions
      typically began with papules or plaques and grew to form nodules with satellite
      lesions and resolved with fibrotic plaques before complete remission. No patient
      had lymphadenopathy or extracutaneous lesions during follow-up (mean 50.5
      months). At the end of follow-up, the lesions in four patients had completely
      resolved irrespective of treatment; two patients had persistent lesions. The
      histopathological pattern of the main infiltrate, the components of cells and the
      stromal responses showed dynamic changes according to the duration of lesions.
      The characteristic Rosai-Dorfman cells (RD cells) were found in association with
      a nodular or diffuse infiltrate in 15 lesions (71%). Four lesions (19%)
      demonstrated a patchy/interstitial pattern. One lesion (5%) assumed the pattern
      of a suppurative granuloma. RD cells were less readily found in these atypical
      patterns. Conspicuous proliferation of histiocytes associated with RD cells was
      found in three lesions, including xanthoma, localized Langerhans cell
      histiocytosis and xanthogranuloma. Along with lymphocytes, plasma cells were
      present in all lesions, often in large numbers with occasional binucleated or
      trinucleated cells. Variably found in the lesions were neutrophils (nine lesions,
      43%) and eosinophils (13 lesions, 62%). The former occasionally formed
      microabscesses, while the latter were often few in number. Vascular proliferation
      was a relatively constant feature (90%). Fibrosis was found in 10 lesions (48%).
      CONCLUSIONS: Our study further confirms that C-RDD is a distinct entity with
      different age and possibly race distributions from RDD. Compared with its nodal
      counterpart, C-RDD demonstrates a wider histopathological spectrum with different
      clinicopathological phases depending on duration of the lesions. Awareness of
      these features is helpful in making a correct diagnosis. The associations of C
      RDD with other histiocytoses may have important implications for the pathogenesis
      of this rare histiocytosis.

PMID- 16433798
TI  - Confluent and reticulate papillomatosis (Gougerot-Carteaud syndrome): a
      minocycline-responsive dermatosis without evidence for yeast in pathogenesis. A
      study of 39 patients and a proposal of diagnostic criteria.
AB  - BACKGROUND: Confluent and reticulate papillomatosis (CRP) (Gougerot-Carteaud
      syndrome) is a disorder that has been characterized in only small cohorts of
      patients. OBJECTIVES: Better to characterize the clinical and pathological
      findings of the disorder. METHODS: We retrospectively reviewed the clinical
      presentation, response to treatment and histological findings of patients
      presenting to Mayo Clinic (Rochester, MN, U.S.A.) with CRP. RESULTS: The disorder
      was diagnosed in 39 patients between 1972 and 2003. Mean age at onset of the skin
      eruption was 15 years (range 8-32); 21 patients (54%) were male; most were white;
      most (33) presented for reasons of cosmesis; and eight described the rash as
      mildly pruritic. At presentation, the skin eruption had been present for a mean
      of 3.1 years (range 3 months-20 years) and had been recalcitrant to treatment,
      including antifungal treatment. Typical objective findings were scaling brown
      macules and patches and velvety papules and plaques, reticulated and
      papillomatous at least in part, involving the upper trunk, axillae and neck. The
      most frequent initial diagnostic impressions were tinea versicolor, acanthosis
      nigricans and CRP. Scales in 32 cases were examined with potassium hydroxide:
      eight (25%) showed hyphae, and 24 (75%) did not. Skin biopsy specimens from 21
      patients showed variable degrees of hyperkeratosis, acanthosis and
      papillomatosis. Minocycline was prescribed for 22 patients, of whom 14 of 18
      (78%) had complete clearing of the skin eruption and four (22%) a partial
      response. The skin eruptions recurred after stopping treatment in six patients.
      CONCLUSIONS: CRP occurs predominantly in young adults and teenagers, with
      cosmetically displeasing brown scaling patches and plaques affecting the neck,
      upper trunk and axillae. Frequently, the diagnosis is delayed and the disorder
      not recognized by physicians, including dermatologists. Clinically, the eruption
      is most often confused with tinea versicolor. Potassium hydroxide staining of the
      scale is negative in the majority of cases, implying that fungi are not involved
      in the pathogenesis of this condition, as has been previously proposed. It is
      important to recognize this disorder, because minocycline therapy is highly
      effective in most patients. Criteria for the diagnosis are proposed.

PMID- 16433799
TI  - Quality of life in patients with chronic urticaria is differentially impaired and
      determined by psychiatric comorbidity.
AB  - BACKGROUND: Chronic urticaria (CU), one of the most common skin disorders, is
      characterized by spontaneous recurrent bouts of weals and pruritus and associated
      with severely impaired quality of life (QoL). OBJECTIVES: To determine what
      aspects of life quality are affected and to characterize the factors that impact
      on QoL in CU patients. SUBJECTS AND METHODS: This interdisciplinary
      interview/questionnaire-based study included 100 patients admitted to a
      University Hospital Dermatology Department for the identification of underlying
      causes of CU; 96 healthy subjects matched for age and sex were used as controls.
      QoL was assessed using Skindex-29, a validated instrument to measure the effects
      of skin disease on overall QoL (composite score) and three defined QoL aspects
      (emotions, symptoms, functioning). RESULTS: CU patients exhibited markedly
      reduced overall QoL compared with healthy control subjects. CU had distinct
      effects on the three QoL aspects assessed (functioning = emotions > symptoms).
      The age or sex of patients, the absence or presence of angio-oedemas, and the
      duration or cause of CU did not significantly influence QoL impairment.
      Interestingly, psychiatric comorbidity (depression, anxiety, somatoform
      disorders) was associated with a more pronounced reduction of QoL compared with
      CU patients without a psychiatric diagnosis and the severity of psychiatric
      disease was found to correlate with QoL impairment. CONCLUSIONS: Our data confirm
      that overall QoL is markedly reduced in CU patients. Social functioning and
      emotions were found to be the areas of QoL most affected in CU patients.
      Psychiatric comorbidity significantly increased QoL impairment, whereas QoL in CU
      patients was not significantly affected by age or sex, the absence or presence of
      angio-oedema, or the course or cause of CU.

PMID- 16433800
TI  - Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi.
AB  - BACKGROUND: Based on the dermoscopic classification of acquired melanocytic
      naevi, six different dermoscopic types can be distinguished by morphology
      (globular, globular-reticular, globular-homogeneous, reticular, reticular
      homogeneous, homogeneous) and by pigment distribution (uniform, central
      hyperpigmentation, central hypopigmentation, peripheral hyperpigmentation,
      peripheral hypopigmentation, multifocal hyper/hypopigmentation). It has been
      suggested that most individuals harbour one predominant dermoscopic type among
      their naevi. OBJECTIVES: To evaluate whether the age of the patient influences
      the predominant naevus pattern observed in individuals with multiple acquired
      melanocytic naevi. METHODS: Individuals were recruited from the pigmented skin
      lesion clinic in Graz between July 2000 and February 2001. Individuals with at
      least 10 melanocytic naevi were selected consecutively until a total of 10
      individuals in each of five age groups was obtained. Age groups were: 0-15 years,
      16-30 years, 31-45 years, 46-60 years and > 60 years. Digitized images of
      acquired melanocytic naevi, defined as benign melanocytic proliferations having a
      diameter of at least 5 mm with a macular component and which were not apparent
      within the first year of life, were evaluated by dermoscopic criteria. The
      associations of dermoscopic features as a function of patient age were analysed.
      We calculated absolute numbers and frequencies, given as percentages, as well as
      predominance of the dermoscopic types of naevi in the different age groups.
      RESULTS: Analysis of 1268 naevi revealed that the globular pattern predominated
      in the youngest age group. By contrast, the reticular and/or homogeneous patterns
      were increasingly exhibited in naevi from older individuals (older than 15
      years). Uniform pigmentation was most common in melanocytic naevi in the youngest
      age group, while central hyperpigmentation was predominantly seen in the group of
      individuals aged 16-30 years. CONCLUSIONS: The predominance of dermoscopic types
      of melanocytic naevi varies according to the individual's age. Awareness of the
      age-related dermoscopic predominance of melanocytic naevi might allow more
      accurate recognition of dermoscopic patterns of melanocytic skin lesions that are
      unusual with respect to the individual's age. This observation may help in the
      early recognition of some 'banal'-appearing melanomas. Furthermore, the
      observations made in this study raise interesting questions regarding naevus
      evolution.

PMID- 16433801
TI  - Bispectral fluorescence imaging of aggressive basal cell carcinoma combined with
      histopathological mapping: a preliminary study indicating a possible adjunct to
      Mohs micrographic surgery.
AB  - BACKGROUND: Fluorescence imaging is an attractive diagnostic technique for skin
      tumour demarcation with potential to move to clinical use. Bispectral
      fluorescence imaging combines skin autofluorescence with delta-aminolaevulinic
      acid-induced fluorescence. To evaluate the technique, fluorescence data must be
      compared with the histopathological extent of the tumour, which is the purpose of
      the current study. OBJECTIVES: To investigate the agreement between bispectral
      fluorescence images and the histopathological tumour boundary of ill-defined
      basal cell carcinomas (BCCs). After fluorescence imaging the tumours were removed
      using Mohs micrographic surgery (MMS) to obtain histopathological maps of the
      tumour boundaries. METHODS: Twelve patients with aggressive BCC of mean diameter
      16 mm (range 5-32) in the face were included in the study. The patients were
      subjected to bispectral fluorescence imaging within the 2 months prior to MMS.
      The fluorescence images and histopathological maps were aligned using image
      warping. RESULTS: Five patients (42%) showed good agreement with the
      histopathological mapping and the remaining seven patients (58%) showed partial
      agreement. Bispectral investigation combining autofluorescence with
      protoporphyrin IX (PpIX) fluorescence generally yielded better agreement with the
      histopathological boundaries of the tumours compared with using only the PpIX
      fluorescence. CONCLUSIONS: In this preliminary study the fluorescence has been
      compared with the histopathological tumour boundaries. The result implies that
      the technique can be applied as a useful tool for indicating tumour boundary of
      aggressive BCCs. Further refinement is needed to be able to indicate the exact
      tumour border.

PMID- 16433802
TI  - Melanoma of the ear: prognostic factors and surgical strategies.
AB  - BACKGROUND: The ear's specific anatomical and lymphatic characteristics impose
      special requirements on the treatment of melanoma of the ear. OBJECTIVES: The aim
      of this prospective study was to define prognostic factors for melanoma of the
      ear and to evaluate surgical strategies for excision margins, histological
      evaluation and sentinel lymph node biopsy (SLNB) in order to achieve better
      cosmetic and functional results. PATIENTS AND METHODS: One-hundred and sixty-one
      patients with stage I/II melanoma of the external ear were treated in the
      Department of Dermatology, University of Tuebingen, from March 1976 to March 2004
      (median follow-up 62 months). Malignant melanoma of the external ear represented
      3% of the stage I/II cutaneous melanomas and 20% of the stage I/II head and neck
      melanomas recorded in the Melanoma Registry of the Department of Dermatology at
      the University of Tuebingen. Twenty of 42 lentigo maligna melanomas (LMM)
      underwent conventional histological evaluation, 22 underwent complete three
      dimensional histology of excision margins (3D histology) in a paraffin-technique,
      i.e. micrographic surgery. SLNB was performed in 28 patients with melanomas
      thicker than 1.0 mm. Clinical, histological and surgical risk factors were
      evaluated by univariate and multivariate analysis. RESULTS: The median thickness
      of the tumours in the present study was 1.08 mm (mean 1.51 mm; range 0.18-8.50
      mm), and the median excision margins were 11.0 mm (mean 12.61 mm; range 2.0-31.0
      mm). The 3-year disease-specific survival rate was 98%, and the 3-year recurrence
      free survival rate was 83%. Tumour thickness and invasion level were the only
      risk factors significant for disease-specific survival. Tumour thickness,
      location of the tumour and extent of excision margins were independently
      significant risk factors for recurrence-free survival. LMMs removed surgically
      with accompanying 3D histology were thicker than those examined by conventional
      histology (median 0.93 mm vs. 0.83 mm). The use of surgery with 3D histology,
      i.e. micrographic surgery, made it possible to reduce the excision margins
      (median 5 mm vs. 10 mm) without an increased risk of recurrence. Two of 29 SLNBs
      were positive (6.9%). There were six preregional recurrences after negative SLNB
      and one after positive SLNB. None of the patients who underwent SLNB died of
      melanoma-related causes during the observation period. CONCLUSIONS: This is the
      largest series of ear melanomas reported so far. The overall survival depended
      only on the tumour thickness and Clark level of invasion. Local recurrence was
      more frequent with smaller excision margins, but this did not influence the
      overall survival. Smaller excision margins under 3D-histological control did not
      carry an increased risk of local recurrence. Our results do not permit
      conclusions regarding the prognostic impact of SLNB for patients with melanoma of
      the ear.

PMID- 16433803
TI  - The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema
      multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.
AB  - BACKGROUND: Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic
      epidermal necrolysis (TEN) are determined by a dysregulation of cellular
      immunity. OBJECTIVES: To evaluate the effector role of cellular immunity and the
      involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and
      SJS/TEN. METHODS: Biopsy specimens from eight patients with EM and six with
      SJS/TEN were stained for immunohistochemical examination using the alkaline
      phosphatase/antialkaline phosphatase method. The monoclonal antibodies used
      included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and
      myeloperoxidase. RESULTS: The cellular infiltrate in both EM and SJS/TEN lesions
      was composed mainly of T lymphocytes and CD68+ macrophages. We also detected
      large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and
      TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there
      were numerous CD40L+ cells in SJS/TEN but much fewer in EM. CONCLUSIONS:
      Activated T lymphocytes and macrophages, but also neutrophils, are presumably the
      main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The
      Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM,
      where this apoptotic pathway presumably does not play a pivotal role in the
      epidermal damage. We suggest that the CD40/CD40L system may represent an
      important pathway of induction of SJS/TEN lesions, while in EM it would
      contribute to the immunoinflammation only as a second-line mechanism.

PMID- 16433804
TI  - Age, gender, quality of life and psychological distress in patients hospitalized
      with psoriasis.
AB  - BACKGROUND: Psoriasis has a great impact on the quality of life of patients, and
      the ageing population is an important public health issue. OBJECTIVES: To
      investigate whether older patients with psoriasis have a different impairment in
      quality of life compared with younger patients, considering level of severity,
      duration of disease, gender and psychological distress. METHODS: The study was
      performed between February 2000 and February 2002 at the inpatient wards of the
      Dermatological Institute IDI-IRCCS, Rome, Italy, in the framework of a large
      project on clinical, epidemiological, emotional and quality of life aspects of
      psoriasis (IMPROVE study). This is a hospital-based cross-sectional study, with
      measures of quality of life (Skindex-29, Dermatology Life Quality Index and
      Psoriasis Disability Index) and of psychological distress, generic (12-item
      General Health Questionnaire) and psoriasis-related (Psoriasis Life Stress
      Inventory), all self-assessed by patients. We compared the mean scores of each
      quality of life instrument in patients aged < 65 years and >/= 65 years, in
      subsets of patients based on clinical and sociodemographic characteristics.
      RESULTS: We analysed 936 patients hospitalized at IDI-IRCCS with a diagnosis of
      psoriasis. Quality of life was significantly more impaired in the older group for
      all the Skindex-29 scales, and psychological distress was higher in older
      patients. In particular, older women suffering from anxiety or depression had the
      greatest impairment in quality of life. The results were somewhat different using
      the other quality of life instruments. CONCLUSIONS: These results should alert
      dermatologists that similar levels of clinical severity in psoriasis may be
      associated with different levels of quality of life and psychological distress of
      patients. Particular attention should be devoted to older patients, and
      especially to older women.

PMID- 16433805
TI  - Psoriasis in Swedish conscripts: time trend and association with T-helper 2
      mediated disorders.
AB  - BACKGROUND: According to the T-helper (Th)1/Th2 paradigm, it has been argued that
      Th1-dominated diseases such as psoriasis and Th2-dominated diseases such as
      asthma and hay fever should be mutually exclusive, as the immune regulatory
      cells, Th1 and Th2, cross-regulate each other. An increase in asthma and hay
      fever has occurred in Sweden over the past four to five decades, but the time
      trend for psoriasis is not clear. OBJECTIVES: To assess the prevalence of
      psoriasis in young Swedish men over a period of three decades and the association
      between psoriasis and allergic disorders. METHODS: Register study based on data
      from the Swedish Military Service Conscription Register and the Total Population
      and the Population and Housing Censuses. Psoriasis, asthma (with and without
      allergic rhinitis) and allergic rhinitis at conscription were studied in 1 226
      193 male conscripts in successive cohorts born between 1952 and 1977. RESULTS:
      The prevalence of psoriasis was about 0.5% and it remained stable over three
      decades. Conscripts with psoriasis and their siblings were less likely to have
      eczema. The reduced risk of eczema in conscripts with psoriasis was unchanged
      over time. A reduced risk of allergic rhinitis was also demonstrated in
      conscripts with psoriasis and their siblings but only in the most recent birth
      cohort born between 1970 and 1977. CONCLUSIONS: A strong genetic influence may
      explain the unchanged prevalence of psoriasis in Swedish conscripts. A genetic
      predisposition for psoriasis may confer partial protection from eczema and
      allergic rhinitis. The inverse relationship between allergic rhinitis and
      psoriasis appeared to be a recent phenomenon.

PMID- 16433806
TI  - Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body
      applications, with and without ultraviolet irradiation.
AB  - BACKGROUND: Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is
      commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and
      can be found in the urine. The amount varies between 0.4% and 2%. This seems to
      be the main metabolic pathway in rats. OBJECTIVES: To investigate the total
      amount of BZ-3 excreted in the urine after repeated topical whole-body
      applications of a sunscreen and to see if UV radiation has any effect on the
      amount excreted. METHODS: Twenty-five volunteers applied a commercially available
      sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was
      measured during those 5 days and during a further 5 days after the last
      application. They were divided into groups A (unirradiated) and B. Group B
      received UV radiation according to skin type: UVA between 400 and 707 J cm(-2),
      and UVB between 0.46 and 2.0 J cm(-2). BZ-3 in urine was analysed with a high
      performance liquid chromatography method. RESULTS: The volunteers excreted 1.2
      8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant
      difference between the two groups (P < 0.99, t-test). CONCLUSIONS: We show that a
      large amount of BZ-3 is absorbed. BZ-3 is accumulated in the body as the
      volunteers excreted BZ-3 5 days after the last application.

PMID- 16433807
TI  - Synergistic antimicrobial activity by combining an allylamine with benzoyl
      peroxide with expanded coverage against yeast and bacterial species.
AB  - BACKGROUND: Dermatophyte infections can be polymicrobial. Topical antifungal
      therapies offer limited coverage of yeasts and Gram-positive and Gram-negative
      bacteria. Moreover, the increased usage of these topical antimicrobial agents has
      resulted in the development of resistant cases. Benzoyl peroxide (BP), used in
      concert with antimicrobial agents containing an accessible tertiary amine, has
      previously been shown to increase radical activity and biological effect.
      OBJECTIVES: To determine the applicability of using the tertiary amine
      terbinafine in concert with BP in dermatophyte and mixed skin infections by means
      of in vitro testing. METHODS: In this preliminary in vitro study, the effect of
      BP, alone and in combination with terbinafine, was tested against Candida
      albicans, Pseudomonas aeruginosa and Staphylococcus aureus isolates following a
      checkerboard modification of the National Committee for Clinical Laboratory
      Standards M27-A2 and M7-A6. The individual minimum inhibitory concentrations of
      terbinafine, BP, and the combination, were determined against each isolate.
      RESULTS: The combination of BP with terbinafine led to additive activities
      against the majority of Candida albicans isolates tested and additionally
      expanded the bacterial coverage of terbinafine. CONCLUSIONS: The combination of
      antifungal agents bearing a tertiary amine with BP may have benefit in
      polymicrobial infections, given its wider antimicrobial coverage. Further
      appreciation of this mechanism of catalysis of BP radical formation by certain
      antimicrobials and other tertiary amine-containing compounds may lead to the
      discovery of improved treatments for several dermatological conditions.

PMID- 16433808
TI  - Apolipoprotein E gene polymorphisms are associated with psoriasis but do not
      determine disease response to acitretin.
AB  - BACKGROUND: Psoriasis is associated with abnormal plasma lipid metabolism and a
      high frequency of cardiovascular events. Increased lipid levels are also seen in
      patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants
      have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal
      individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define
      the three common ApoE alleles e2, e3 and e4. OBJECTIVES: To test the hypothesis
      that particular ApoE polymorphism(s) are associated with psoriasis and that
      specific ApoE allelic variant(s) may be a marker for predicting disease response
      to acitretin. METHODS: DNA was genotyped for ApoE polymorphisms using a
      radioactive hybridization technique in cohorts of patients with psoriasis,
      including patients with chronic plaque psoriasis (CPP, n = 212), guttate
      psoriasis (GP, n = 94), palmoplantar pustulosis (PPP, n = 101), controls (n =
      137), acitretin responders (n =106) and acitretin nonresponders (n = 84).
      RESULTS: The frequency of the e4 allele (+3937C/+4075C) was significantly higher
      in patients with CPP and GP than in controls (P = 0.008 and P = 0.02,
      respectively). There was no significant difference in allele frequencies between
      patients with PPP and controls. Allelic distribution was similar in acitretin
      responders and nonresponders. CONCLUSIONS: These data demonstrate an association
      between the Apo e4 allele and CPP and GP, suggesting a possible pathogenic role
      for ApoE in psoriasis. Our results do not support a link between disease response
      to acitretin and the e2, e3 or e4 allelic variants of ApoE.

PMID- 16433809
TI  - Clobetasol propionate 0.05% in a novel foam formulation is safe and effective in
      the short-term treatment of patients with delayed pressure urticaria: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Delayed pressure urticaria (DPU) is characterized by the appearance
      of typical painful skin lesions (weals) after pressure stimulus. Oral
      corticosteroids are effective treatments but long-term therapy is problematic. A
      new topical formulation of clobetasol propionate 0.05% in thermophobic foam (CF)
      (Olux) has recently become available. The foam is easy to apply, with low skin
      residues. OBJECTIVES: To evaluate in a double-blind placebo-controlled trial the
      efficacy, tolerability and safety of CF in the topical treatment of DPU. METHODS:
      Twenty-six subjects with a positive history of DPU (13 men, mean age 44 years)
      were enrolled in a 4-week trial. CF or the corresponding placebo were applied
      twice daily. Drug application was performed in the most affected areas and in a
      target area where a standardized pressure challenge test was performed at
      baseline and at week 4. Efficacy was evaluated by scoring skin lesions regarding
      erythema, oedema and itching (0, no sign; 4, severe signs) and by calculating the
      area of the pressure challenge-induced lesion. Safety was evaluated by measuring
      plasma levels of adrenocorticotropic hormone (ACTH) and cortisol. RESULTS: CF
      significantly (P = 0.0001) reduced lesion area by 84% in comparison with baseline
      values and by 97% in comparison with the placebo group values. Lesion area in the
      CF group was reduced from 144 cm(2) to 21 cm(2) at the end of the study. No
      significant differences in lesion area and clinical lesion scores were observed
      in the placebo group (lesion area 201 cm(2) at baseline; 216 cm(2) after 4
      weeks). A significant clinical improvement was observed in all treated skin areas
      in the CF group. Mean +/- SD erythema score was reduced by CF from 1.8 +/- 0.6 at
      baseline to 0.6 +/- 0.5 at the end of the treatment (P = 0.001). Similar
      modifications were observed also for oedema (from 1.6 +/- 0.6 to 0.2 +/- 0.5) and
      itching score. Nonsignificant modifications of plasma levels of ACTH, cortisol
      and glucose were observed in both study groups, in comparison with baseline
      values. No adverse events were recorded during the trial in either treatment
      group. CONCLUSIONS: CF is effective, safe, convenient and well tolerated in the
      short-term treatment of DPU.

PMID- 16433810
TI  - Assessment of the efficacy of cryosurgery in the treatment of granuloma faciale.
AB  - BACKGROUND: Granuloma faciale (GF) is an uncommon dermatosis of unknown
      pathogenesis. Multiple treatments have been proposed with varying results. We
      report nine cases treated successfully with cryosurgery and we review the
      literature. OBJECTIVES: To study the efficacy, tolerability and safety of
      cryosurgery techniques in the treatment of GF. METHODS: Nine immunocompetent
      adults with GF were treated by cryosurgery. The initiation of the therapy was
      preceded by a 60-day washout period in all subjects using other medication. Two
      different techniques were used (open-spray and contact cryo-probe). RESULTS: All
      patients were treated successfully. Apart from mild postinflammatory
      hypopigmentation in two patients that resolved within 4 months, no other adverse
      event was mentioned. During an average 24-month follow-up period after the
      integration of therapy, no recurrences were observed. CONCLUSIONS: Cryosurgery is
      an efficient, safe, inexpensive, easily used method for this uncommon dermatosis,
      which can be proposed as a treatment of first intention.

PMID- 16433811
TI  - Lichen planus is associated with human herpesvirus type 7 replication and
      infiltration of plasmacytoid dendritic cells.
AB  - BACKGROUND: Lichen planus (LP) is a common inflammatory skin disease of unknown
      aetiology. Viral causes have been suggested. OBJECTIVES: To find candidate
      viruses associated with LP. METHODS: Lesional and nonlesional skin samples,
      peripheral blood mononuclear cells and serum were obtained from patients with LP.
      Ultrastructural, viral DNA, immunohistochemical and serological analyses were
      performed, and comparisons were made with psoriatic and normal skin. RESULTS:
      Electron microscopy revealed typical 120-200-nm enveloped particles with a 100-nm
      nucleus resembling human herpesvirus (HHV) virions both in dermis and in
      epidermis of lesional LP tissue. HHV-7 DNA was found in 11 of 18 lesional LP
      samples, as opposed to only one of 11 nonlesional LP samples (P =0.06), two of 11
      lesional psoriasis samples (P = 0.05) and none of four normal skin samples. No
      relation was found between LP skin and DNA of other known HHVs (HHV-1-6 and 8).
      With immunohistochemistry, significantly more HHV-7+ cells were found in lesional
      LP epidermis than in normal epidermis. Lesional LP dermis contained significantly
      more HHV-7+ cells than nonlesional LP, psoriatic or normal dermis. Moreover, LP
      skin contained overwhelmingly and consistently more plasmacytoid dendritic cells
      (upregulated in virally induced conditions) than nonlesional LP samples.
      CONCLUSIONS: We conclude that HHV-7 replicates in LP lesions, but not in
      psoriasis, another inflammatory skin condition. HHV-7 is possibly involved in the
      pathogenesis of LP. These preliminary data make further research on this topic of
      interest.

PMID- 16433812
TI  - Linear Darier disease with herpes zoster superinfection treated successfully by
      brivudine.
AB  - We report the case of a human immunodeficiency virus-positive patient presenting
      linear Darier disease with varicella-zoster virus superinfection following the
      lines of Blaschko. The lesions healed after treatment with brivudine.

PMID- 16433813
TI  - A Chilean boy with severe photosensitivity and finger shortening: the first case
      of homozygous variegate porphyria in South America.
AB  - A 7-year-old Chilean boy presented with severe photosensitivity, blistering,
      erosions and scarring on sun-exposed areas of the body since the age of 6 months.
      Additionally, he showed a short stature and shortening of the fingers. Laboratory
      examination revealed greatly elevated protoporphyrin levels in the blood. Such
      biochemical findings can be observed in homozygous variants of usually autosomal
      dominantly inherited acute porphyrias such as variegate porphyria (VP) and
      hereditary coproporphyria, which usually do not become manifest before the second
      or third decade of life in heterozygotes. Using polymerase chain reaction-based
      techniques we identified a missense mutation in exon 7 on the paternal allele and
      a frameshift mutation in exon 13 on the maternal allele of the protoporphyrinogen
      oxidase gene that harbours the mutations underlying VP. This is the first
      homozygous case of VP in South America. As VP represents the most frequent type
      of acute porphyria not only in Chile but also in South Africa, more such cases
      could be expected in the future, particularly because a founder mutation for this
      disease has already been described in the Chilean and South African population.

PMID- 16433815
TI  - Metastatic extramammary Paget's disease successfully controlled with tumour
      dormancy therapy using docetaxel.

PMID- 16433814
TI  - Sezary syndrome associated with granulomatous lesions during treatment with
      bexarotene.
AB  - Sezary syndrome (SS) is a leukaemic variant of cutaneous T-cell lymphoma (CTCL).
      We report a patient with SS who developed granulomatous lesions. These lesions
      broke out during treatment with bexarotene when the disease had appeared to
      stabilize. After a partial clinical remission the disease showed rapid
      progression and finally led to the patient's death. This contradicts the initial
      assessment, which considered the granulomatous inflammation as a good prognostic
      factor in CTCL.

PMID- 16433816
TI  - Eruptive angiomas associated with graft-versus-host disease.

PMID- 16433817
TI  - Efficacy of famciclovir in the treatment of oral hairy leukoplakia.

PMID- 16433818
TI  - Expression of endoglin and the activin receptor-like kinase 1 in skin suggests a
      role for these receptors in normal skin function and skin tumorigenesis.

PMID- 16433819
TI  - Flexural pigmentation with multiple lentigines: a new primary pigmentary
      disorder?

PMID- 16433820
TI  - Is onychoblastoma really a new entity?

PMID- 16433821
TI  - A new multiple site marking grid for botulinum toxin application in the treatment
      of axillary hyperhidrosis.

PMID- 16433823
TI  - Thiodiglycolic acid and dermatological reactions following S-carboxymethyl-L
      cysteine administration.

PMID- 16433827
TI  - Preeclampsia: the death of Goliath.
AB  - In this review, a novel and unifying pathophysiologic mechanism of preeclampsia
      is presented whereby a minimal excess of placental immune complex production
      versus removal causes a proinflammatory autoamplification cascade of trophoblast
      apoptosis/necrosis and oxidative stress, culminating in clinical preeclampsia.
      This concept immediately leads to a plethora of new and robust therapeutic
      strategies.

PMID- 16433828
TI  - Neutrophil function during pregnancy: is nitric oxide production correlated with
      superoxide production?
AB  - PROBLEM: Oxygen radical formation by neutrophils during pregnancy is not well
      studied. METHOD OF STUDY: We studied neutrophil-derived superoxide anion (O) and
      nitric oxide (NO) values in 75 normal pregnant women, 12 postpartum women, and 10
      non-pregnant women. O production was measured by the superoxide dismutase
      inhibitable reduction of ferricytochrome c. NO production was measured by
      accumulation of the stable end product nitrite using a modified Griess reaction
      method. RESULTS: O production of neutrophils stimulated by chemotactic peptide
      was significantly enhanced in the early second trimester of pregnancy. l-arginine
      analogue-inhibitable nitrite production was induced in neutrophils from pregnant
      women, but not from postpartum and non-pregnant subjects. In third-trimester
      subjects but not non-pregnant subjects, neutrophils pre-treated with l-arginine
      analogues enhanced O production compared with untreated neutrophils. CONCLUSION:
      These findings indicate that O and NO production by neutrophils during pregnancy
      were modulated separately, whereas neutrophil-derived NO might function as a
      regulator of O.

PMID- 16433829
TI  - Killer immunoglobulin-like receptor and human leukocyte antigen expression as
      immunodiagnostic parameters for pelvic endometriosis.
AB  - PROBLEM: We investigated host immunologic responses to endometriosis by comparing
      immune cell surface antigens in peripheral blood (PB) and peritoneal fluid (PF)
      from women with endometriosis with those in PB and PF from other patients. METHOD
      OF STUDY: Japanese women with endometriosis (n = 56) were compared with controls
      with other laparoscopic diagnoses (n = 68). PB and PF were collected at the time
      of laparoscopy for flow cytometry. RESULTS: No significant difference in
      phenotypic parameters of T cells (CD3, CD4, and CD8), B cells (CD19), natural
      killer (NK) cells (CD56), or monocytes/macrophages (CD14) was seen between women
      with and without endometriosis. However, increased killer immunoglobulin-like
      receptor (CD158a) expression by NK cells and decreased human leukocyte antigen
      (HLA)-ABC and -DR expression by macrophages, all suggesting decreased functional
      activation were found in endometriosis. These markers showed significant
      association with endometriosis by odds ratio, logistic regression, and decision
      tree analyses. CONCLUSIONS: Increased CD158a(+) NK cells in PB and PF indicated
      decreased NK cell cytotoxicity in endometriosis, while decreased HLA expression
      on PF macrophages suggested impaired antigen presentation. Thus, aberrant immune
      responses by NK cells and macrophages may represent risk factors for
      endometriosis.

PMID- 16433830
TI  - The impact of dydrogesterone supplementation on serum cytokine profile in women
      with threatened abortion.
AB  - PROBLEM: The role of increased Th1 cytokine expression in pregnancy failure has
      been questioned recently. The therapeutic value of progestogens in threatened
      abortion (TA) is still debated. The aim of this prospective study was to compare
      serum cytokine [tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 and IL-10]
      concentrations in women with TA to those in women with normal pregnancy and to
      evaluate the impact of dydrogesterone supplementation in the former group on
      cytokine concentration. METHODS OF STUDY: Twenty-seven threatened aborters were
      treated for 10 days with dydrogesterone (30-40 mg/day). Sixteen healthy pregnant
      controls received no treatment. Serum cytokine concentrations were measured twice
      in both groups by enzyme-linked immunosorbent assay. RESULTS: Mean serum
      concentrations of Th1- and Th2-type cytokines in women with TA did not differ
      from those in women with normal pregnancy at first and second sampling. After
      dydrogesterone supplementation, mean TNF-alpha/IL-10 ratio changed from 1.08 to
      1.75 while IL-12/IL-10 ratio remained almost the same (0.56-0.61) in the
      threatened aborters group and did not differ from those in healthy women.
      CONCLUSIONS: The results of this study indicate that peripheral cytokine
      production in threatened aborters does not differ from that observed among
      healthy pregnant women. The protective effect of dydrogesterone supplementation
      in threatened aborters is manifested via restoring progesterone-induced blocking
      factor concentration rather than controlling cytokine production.

PMID- 16433831
TI  - The progesterone-induced blocking factor modulates the balance of PKC and
      intracellular Ca.
AB  - PROBLEM: Progesterone-induced blocking factor (PIBF) induces Th2 biased cytokine
      production; therefore, this study investigates the effects of PIBF on the protein
      kinase C (PKC)/Ca(++) system - which plays a key role in Th1/Th2 differentiation.
      METHOD OF STUDY: Proteins from PIBF-treated cells were reacted on Western blots
      with phospho-specific antibodies recognizing different PKC izoforms.
      Intracellular free calcium was measured by flow cytometry. RESULTS: Both
      interleukin (IL)-4 and PIBF induced PKC phosphorylation, which was abrogated by
      anti-IL-4Ralpha or anti-PIBF immunoglobulin G pre-treatment. PIBF treatment did
      not alter intracellular Ca(++) levels. Inhibition of PKCzeta or PKCtheta
      phosphorylation, but not that of PKCalpha/beta resulted in the loss of STAT6 and
      Jak1 phosphorylation by PIBF. CONCLUSIONS: Our data show that PIBF phosphorylates
      PKC via binding to the IL-4R, without affecting intracellular Ca(++).
      Phosphorylation of PKCzeta and PKCtheta is required for Jak1 and STAT6
      activation, whereas PKCalpha/beta is not involved. These findings explain the
      mechanism by which PIBF supports a Th2 dominant cytokine pattern.

PMID- 16433832
TI  - Cytokine genotyping in preeclampsia.
AB  - PROBLEM: Considering that cytokines are involved in preeclampsia (PE)
      pathogenesis and that cytokine gene polymorphism may affect cytokine production,
      our purpose was to investigate the association of PE with tumor necrosis factor
      (TNF)-alpha (-308), transforming growth factor-beta1 (+10; 25), interleukin (IL)
      10 (-1082), IL-6 (-174), and interferon-gamma (+874) polymorphisms. METHOD OF
      STUDY: Genotyping was performed in women with PE (56 White and 95 non-White
      women) and in women without obstetric pathology (92 White and 97 non-White
      women). Data were analyzed by the chi-square or Fisher exact test. We performed a
      meta-analysis encompassing these and results from other laboratories on the
      association of TNF-alpha polymorphisms and PE. RESULTS: We observed a lower
      frequency of the IL-10 -1082-G/G genotype in White women with PE (PE: 5%; Control
      (C): 15%, P = 0.02) and no association for all other polymorphisms, including
      meta-analysis of TNF-alpha results. CONCLUSION: Our study suggests that PE is
      associated with IL-10-(1082) polymorphism but not with TNF-(308) polymorphism. On
      the basis of meta-analysis, we confirm the need for more studies for the
      evaluation of cytokine genotype in disease.

PMID- 16433833
TI  - Induction of IL-1, in the testes of adult mice, following subcutaneous
      administration of turpentine.
AB  - PROBLEM: Interleukin-1 family is present in the testicular homogenates and its
      cellular compartments. It has been suggested that IL-1 is involved in
      physiological and pathological functions of the testicular tissues. In the
      present study we examined the effect of acute mostly localized inflammation,
      using turpentine, on the expression levels of testicular IL-1 system. METHODS OF
      STUDY: Mice were subcutaneously injected with steam-distilled turpentine or
      saline (control). Three hours to 10 days following the injection, mice were
      killed and testis and spleen were homogenized and examined for interleukin (IL)
      1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) levels by enzyme-linked
      immunosorbent assay and polymerase chain reaction. RESULTS: Subcutaneous
      injection of turpentine induced mice systemic inflammation, as indicated by
      significant increase in serum IL-1beta levels, and IL-1alpha, IL-1beta and IL-1ra
      in spleen homogenates. The levels of IL-1alpha, IL-1beta and IL-1ra were
      significantly induced in testicular homogenates of adult mice following
      subcutaneous injection of turpentine. The significant induction of testicular IL
      1alpha was detected after 3-24 hr of turpentine injection and decreased later
      (after 3-10 days) to levels similar to the control. However, significant
      induction of testicular IL-1beta was detected only after 3-10 days of turpentine
      injection, and for testicular IL-1ra levels was detected after 3 hr to 6 days of
      turpentine injection, and after 10 days the levels were similar to the control.
      These results were also confirmed by mRNA expression of these factors.
      CONCLUSION: Our results demonstrate for the first time the distant effect of
      acute localized inflammation on testicular IL-1 levels. Thus, transient
      inflammatory response to infectious/inflammatory agents at non-testicular sites
      that elicit systemic IL-1 response should be considered during clinical treatment
      as a possible factor of male infertility.

PMID- 16433835
TI  - In vivo correlation between IL-1beta concentration in uterine fluid and integrin
      expression pattern in infertile women.
AB  - PROBLEM: To evaluate the possible correlation between interleukin-1beta (IL
      1beta) and integrin expression. METHOD OF STUDY: Endometrium and uterine fluid
      from 77 infertile women and 24 fertile, healthy control were studied with
      immunohistochemistry and enzyme-linked immunosorbent assay for the presence of IL
      1beta and integrin alphaVbeta3 and alpha4beta1 expression. RESULTS: Highest
      expression of alphaVbeta3 was found in epithelium and glands in endometria from
      fertile women. There was no positive correlation between IL-1beta and integrin
      expression pattern. CONCLUSION: This study confirms the importance of alphaVbeta3
      as molecular marker of receptive phase. Also supports the views that synchrony in
      development of endometrium is necessary for successful nidation. There was
      however, contrary to results of previous in vitro studies, no positive
      correlation between IL-1beta and endometrial integrin patter expression.

PMID- 16433834
TI  - Prebreeding maternal immunostimulation with Freund's complete adjuvant reduces
      placental damage and distal limb defects caused by methylnitrosourea.
AB  - PROBLEM: Immunostimulation reduces murine teratogen-induced birth defects. It is
      unclear if placental improvement contributes to this outcome. The current study
      examined murine placental ultrastructure and fetal limb development following
      maternal methylnitrosourea (MNU) exposure, +/-Freund's complete adjuvant (FCA)
      immunostimulation. METHOD OF STUDY: Two murine strains (CD-1, C57BL/6N) were
      administered MNU on gestation day 9 (GD9), FCA pre-breeding, or FCA + MNU. Fetal
      limb and placental development were examined on GD14. RESULTS: MNU decreased
      placental weight and reduced placental cellular viability; FCA reversed these
      effects. MNU shortened fetal limbs and increased digital defects in both strains.
      Placentas were less damaged in C57BL/6N versus CD-1 mice, and distal limb
      malformations improved only in CD-1 mice. FCA immunostimulation also increased
      pregnancy rate. CONCLUSION: Improved fetal outcome from immune-stimulated mice
      may not be dependent on improved placental morphology. However, placental
      function and morphology in immune-stimulated mice may not directly correlate,
      thus functional improvements should be examined for possible relationship to
      reduced birth defects.

PMID- 16433836
TI  - Pregnancy using gonadotropins and performing intrauterine insemination in a woman
      with hypogonadotropic hypogonadism.
AB  - Hypogonadotropic hypogonadism is one of the causes of infertility. In women with
      hypogonadotropic hypogonadism both follicle-stimulating hormone and luteinizing
      hormone are required to induce optimal follicular growth and steroidogenesis. We
      described a case of singleton pregnancy in a 38-year-old patient, presenting with
      primary hypogonadotropic amenorrhea and empty sella syndrome, treated with human
      menopausal gonadotropins and performing intrauterine insemination in first
      attempt. This therapy led to maturation of two follicles and one of them was
      fertilized. A singleton pregnancy ensued and a normal infant was delivered by
      cesarean section.

PMID- 16433840
TI  - Artificial matrix helps neonatal cardiomyocytes restore injured myocardium in
      rats.
AB  - The purpose of this study was to investigate whether an artificial matrix can
      help neonatal cardiomyocytes restore an injured heart in a rat model of
      myocardial infarction (MI). The left coronary arteries of female Sprague Dawley
      (SD) rats were ligated to create MI models. Ventricular cardiomyocytes from 1- to
      3-day-old SD rats (both sexes) were isolated, cultured, and labeled. Three weeks
      after MI, the animals were randomized into four groups: (i) group cell plus
      matrix (n = 12); (ii) group cell (n = 12); (iii) group matrix (n = 12); and (iv)
      group control (n = 11). Four weeks after transplantation, echocardiography and
      the Langerdoff model were used to assess heart function. Immunohistochemical
      staining and polymerase chain reaction (PCR) were performed to track the
      implanted cardiomyocytes and detect the sex-determining region Y gene on the Y
      chromosome. Histology study and PCR showed that transplanted cardiomyocytes
      survived, formed condensed tissue, and produced connected protein in group cell
      plus matrix. Heart function assessment indicated transplantation of
      cardiomyocytes plus matrix preserved left ventricle wall thickness, fraction
      shortening, and end-systolic internal diameter most effectively.

PMID- 16433841
TI  - In vivo experimental testing of a microaxial blood pump for right ventricular
      support.
AB  - The incidence of isolated right ventricular (RV) failure is rare in
      postcardiotomy patients, but high in patients undergoing implantation of a left
      ventricular assist device or cardiac transplantation. Therefore, we have
      developed a new microaxial flow device and report on our first in vivo animal
      trials. Six healthy adult female sheep weighing 80-90 kg underwent implantation
      of the microaxial blood pump for partial unloading of the right ventricle. This
      pump is a miniaturized rotary blood pump with a diameter of only 6.4 mm and a
      weight of 11 g. The inner volume of the pump is limited to 12 mL, and the inner
      artificial blood contacting surface is 65 cm(2). The pump consists of a rotor
      driven by an incorporated brushless direct current motor, the housing of the
      rotor, the inflow cage, the outflow cannula, and the driveline. At the maximum
      speed of 32,500 rotations/min, a flow of 6 L/min can be delivered. The inflow and
      outflow conduit were anastomosed to the right atrium and the main pulmonary
      artery, respectively. Hemodynamic and echocardiographic data as well as blood
      samples were measured over the whole test period of 7 days. The hearts and lungs
      as well as the pump were explanted for a thorough examination at the end of the
      trial. Systemic arterial blood pressures remained unchanged during the entire
      test period. RV cardiac output was diminished significantly as demonstrated by
      the echocardiographic studies. The number of platelets decreased perioperatively,
      but recovered within the test period. The free hemoglobin was not enhanced
      postoperatively indicating no significant hemolysis. Liver function was only
      slightly impaired due to operative reasons (increase in bilirubin on the first
      postoperative day but normalization within the test period). The pathologic
      examination revealed some clots at the inflow cage and fibrin depositions on the
      impeller as well as on the inner surface of the outflow graft without an
      impairment of pump function. Our results demonstrate that this newly developed
      microaxial blood pump is a promising device for RV support, but it cannot be
      driven without any anticoagulation.

PMID- 16433842
TI  - Vasoconstrictor administration during cardiopulmonary bypass affects acid-base
      balance in infants and children.
AB  - BACKGROUND: In experimental reports, blood flow redistribution occurred during
      cardiopulmonary bypass (CPB) and perfusion pressure was restored by
      vasoconstrictor administration without improving splanchnic perfusion. The
      influence of vasoconstrictor administration during CPB was clinically examined.
      MATERIALS AND METHODS: Twenty-two consecutive pediatric CPB cases of ventricular
      septal defect without blood transfusion were divided into two groups, depending
      upon whether a vasoconstrictor was administered during CPB or not (n = 7 vs. 15).
      Bypass flow and systemic perfusion pressure during CPB were maintained at 2.5
      L/m(2)/min and not lower than 30 mm Hg by vasoconstrictor administration,
      respectively. RESULTS: Although preoperative state and CPB conditions were
      comparable between the two groups, more sodium bicarbonate was administered (P <
      0.05); duration from the operation to extubation was longer (P < 0.05); and bowel
      movement occurred later in the vasoconstrictor-administered group than in the
      control group. CONCLUSIONS: Vasoconstrictor administration during CPB may
      deteriorate the acid-base balance and the postoperative state in infants and
      children.

PMID- 16433843
TI  - Activation of coagulation during hemodialysis: effect of blood lines alone and
      whole extracorporeal circuit.
AB  - Activation of coagulation during hemodialysis (HD) is a relevant clinical
      problem, especially when patients at risk of bleeding are treated. However,
      little is known about the relative contribution of the various components of the
      circuit to the thrombotic process. Thus, an experimental model was developed that
      is aimed at evaluating biochemical markers of coagulation activation at different
      times and sites throughout the HD circuit. A HD blood-tubing set with integrated
      arterial and venous chambers (cartridge-line set) was used, which was added with
      the following sampling points: at the beginning of the arterial line (P1), before
      the blood pump (P2), after the blood pump (P3), and at the end of the venous line
      (P4). A bypass system allowed us to circulate the blood only into the blood lines
      for the first 20 min of the extracorporeal circulation. The extracorporeal
      circuit was rinsed with 1.7 L of heparinized saline (2,500 IU/L) that was
      completely discarded before patient connection. A continuous administration of
      unfractionated heparin (500-800 IU/h) without a starting bolus was adopted as a
      low heparin extracorporeal treatment. Samples were collected before the start of
      the extracorporeal circulation from the fistula needle (T0P0), after 5 (T1), 10
      (T2), and 20 min (T3) from P1, P2, P3, and P4. After 20 min, the blood was
      returned to the patient using only saline and HD was then started, circulating
      the blood through the dialyzer. Further samples were obtained from P1 and P4
      after 5 (T4) and 210 min (T5). Plasma levels of coagulation activation markers
      thrombin-antithrombin complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2)-were
      evaluated in all the samples in 12 stable HD patients. In each patient, the
      activated partial thromboplastin time (APTT) was measured at T0P0 and T1-T5 from
      P1. No significant changes were found at any time as far as F1 + 2 is concerned.
      However, TAT levels increased over time only after the start of HD, suggesting
      that the latter test could be more useful in order to detect coagulation
      activation during HD. The same experiments performed with nonheparin-primed
      extracorporeal circuit showed similar results. The blood lines used did not
      significantly activate coagulation during the first 20 min, whereas only 5 min of
      blood circulation throughout the whole circuit increased TAT values, which still
      remained lower than previous reports, even after 210 min of treatment.

PMID- 16433844
TI  - Clearance studies during subsequent sessions of double filtration plasmapheresis.
AB  - To evaluate the optimal session of double filtration plasmapheresis (DFP) in
      terms of the maximal clearance rates for various serum substances, the laboratory
      parameters of 152 consecutive patients treated with different sessions of DFP
      following a standard protocol on an alternate-day basis was studied.
      Immunoglobulin M (IgM) and lipoprotein cholesterol had the most effective
      clearance by a minimum of two sessions of DFP treatment, and the clearance rates
      remained relatively constant despite the increase in the number of treatment
      sessions, while the clearance rates for other serum proteins increased steadily
      with further treatments. Using the clearance rate of the 2-session group as
      reference, the highest slopes for clearance of albumin, globulin, and
      triglyceride were found in the 4-session group, while the slopes for IgA and IgG
      were highest in the 5-session group. In conclusion, for the clearance of IgM and
      lipoprotein cholesterol, two sessions of DFP treatment are adequate. However, the
      best clearance of IgG and other globulins cannot be achieved until the fourth
      session of DFP treatment. Therefore, a minimum of 4 sessions of DFP treatment at
      2-day intervals is needed for most immunological diseases.

PMID- 16433845
TI  - Tissue engineering approach to the treatment of bone tumors: three cases of
      cultured bone grafts derived from patients' mesenchymal stem cells.
AB  - A novel approach to the treatment of bone tumors using tissue-engineered implants
      is reported in this study. The number of mesenchymal stem cells (MSCs) obtained
      from each patient's bone marrow cells was first increased, and the MSCs were
      forced to differentiate into osteoblasts followed by bone matrix formation on
      hydroxyapatite (HA) ceramics. The strong osteogenic ability of the implants, as
      evidenced by high osteoblastic activity, was confirmed. Consequently, the HA
      surface was covered with the patient's derived cultured osteoblast/bone matrix.
      The tissue-engineered HA was used to fill the patient's bone cavity after tumor
      curettage. Immediate healing potential was found by serial plain radiographs and
      computed tomograhy images, and no adverse reactions were noted in these patients.
      The results indicate that tissue-engineered osteogenic ceramics might be an
      alternative to autologous bone grafts.

PMID- 16433847
TI  - Professor Jaromir Vasku, MD, DSc, 80 years laudation.

PMID- 16433846
TI  - Pharmacokinetics of liposomal amphotericin B during extracorporeal albumin
      dialysis.
AB  - Extracorporeal blood purification techniques such as hemofiltration or albumin
      dialysis can exert a significant, but not easily predictable influence on plasma
      pharmacokinetics of antimicrobial agents. The effect of albumin dialysis on the
      pharmacokinetics of liposomal amphotericin B (AMB) and other lipid-formulated
      drugs has not been investigated so far. Therefore, plasma concentrations of
      liberated and liposomal AMB were measured in a patient, who obtained liposomal
      AMB for suspected invasive mycosis and required albumin dialysis because of
      cholestatic liver failure caused by graft versus host disease after bone marrow
      transplantation. Liberated and liposomal AMB were separated by solid phase
      extraction and measured by high performance liquid chromatography. No excessive
      AMB elimination took place during albumin dialysis. Plasma levels of liposomal
      AMB exceeded those of liberated AMB. Pharmacokinetic data were comparable to
      those obtained previously in patients on hemofiltration and in critically ill
      patients without extracorporeal blood purification.

PMID- 16433849
TI  - The innate and adaptive immune systems in allergy: a two-way street.

PMID- 16433850
TI  - Abnormal fatty acid profiles occur in atopic dermatitis but what do they mean?

PMID- 16433851
TI  - Handle with care: targeting neutrophils in chronic obstructive pulmonary disease
      and severe asthma?
AB  - Neutrophils play an important role in the pathogenesis of airway inflammation in
      both chronic obstructive pulmonary disease (COPD) and severe asthma. Currently
      available drugs have only limited effects on neutrophilic airway inflammation,
      particularily in COPD. Therefore, great efforts are undertaken to address
      neutrophilic inflammation in chronic respiratory disorders, in particular COPD.
      This review summarizes the rationale for anti-neutrophilic treatment in COPD and
      asthma and gives a critical overview of current developments in drug therapy.
      Moreover, unanswered questions and limitations of clinical trial design and
      choice of outcome parameters for proof-of-concept studies with novel anti
      neutrophilic drugs are discussed as well as potential safety issues.

PMID- 16433853
TI  - Serum, cheek cell and breast milk fatty acid compositions in infants with atopic
      and non-atopic eczema.
AB  - BACKGROUND: The major theory implicating diet with allergic diseases is
      associated with altered food consumption and subsequent changes in fatty acid
      composition. OBJECTIVE: To investigate fatty acid compositions among infants with
      atopic and non-atopic eczema and healthy infants and to evaluate the expediency
      of non-invasive cheek cell phospholipid fatty acid composition as a marker in
      patients with eczema. METHODS: Diagnosis of eczema in infants was confirmed
      clinically and by positive (atopic eczema, n=6) or negative (non-atopic eczema,
      n=6) skin prick testing in comparison with controls (n=19). The fatty acid
      compositions of infant cheek cell and serum phospholipids and breast milk total
      lipids were analysed by gas chromatography. RESULTS: The distinction between
      atopic and non-atopic eczema was manifested in cheek cell phospholipids as
      linoleic acid (14.69 (13.67-15.53)% of total fatty acids; the median
      (interquartile range)), the sum of n-6 fatty acids (19.94 (19.06-20.53)%) and the
      sum of polyunsaturated fatty acids (22.70 (21.31-23.28)%) were higher in infants
      with atopic eczema compared with non-atopic eczema (12.69 (10.87-13.93); 17.72
      (15.63-18.91) and 19.90 (17.64-21.06), respectively; P<0.05) and controls (12.50
      (12.16-13.42); 18.19 (17.43-18.70) and 20.32 (19.32-21.03), respectively;
      P<0.05). Serum phospholipid gamma-linolenic acid was lower in both atopic and non
      atopic eczema compared with controls (P<0.05) and additionally eicosapentaenoic
      acid was higher in atopic eczema compared with controls (P<0.05). CONCLUSION:
      These preliminary results suggest differences in fatty acid compositions between
      the two types of eczema, calling for further evaluation in a larger setting. The
      two types of eczema may be regulated by different immunological processes, and
      fatty acids may have a more profound role in the atopic type.

PMID- 16433852
TI  - Signal transducer and activator of transcription 6 down-regulates toll-like
      receptor-4 expression of a monocytic cell line.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4), part of the bacterial lipopolysaccharide
      (LPS) receptor, is an important bridge between innate and adaptive immunity. Our
      previous studies have indicated reduced expression of TLR4 and reduced
      responsiveness to LPS in nasal mucosa of atopic adults compared with non-atopic
      adults. IL-4 and signal transducer and activator of transcription 6 (STAT6),
      which are increased in atopic patients, may have a role in modulating TLR4.
      OBJECTIVE: To examine direct effects of IL-4 and STAT6 on TLR4 expression of U
      937 monocytic cells. METHODS: LPS responsiveness, under different conditions of U
      937 cells was measured by nuclear factor (NF)-kappaB activation of transcription.
      TLR4 mRNA was quantified by real-time PCR and TLR4 surface expression was
      measured by flow cytometry. The promoter and 4.3 kb of the upstream region of
      TLR4 were cloned into a plasmid vector and transiently transfected into U-937
      cells. Transfected cells were incubated with IL-4 and transcriptional activity
      was assayed by the luciferase assay. STAT6 was transfected to evaluate
      overexpression of this transcription factor. Cells were also incubated with
      Tyrphostin AG490 to inhibit tyrosine kinases. RESULTS: NF-kappaB activation by
      LPS was inhibited by IL-4 pre-incubation but not when IL-4 was added at the same
      time as LPS. TLR4 mRNA expression was inhibited by IL-4 as early as 6 h but the
      effect was lost by 24 h. Surface expression of TLR4 was inhibited by IL-4 at 12
      and 24 h, but returned to baseline at 48 h. IL-4 inhibited activity of the TLR4
      promoter as early as 6 h, but, like the mRNA, these effects were transient. STAT6
      overexpression enhanced the inhibition of the TLR4 promoter and prolonged it.
      Inhibition of TLR4 by IL-4 was abolished by pre-incubation with the tyrosine
      kinase inhibitor Tyrphostin AG490. CONCLUSION: Our findings demonstrate that IL
      4, through STAT6, can modulate TLR4 expression and suggests that Th2 cytokines
      can impact on the LPS responsiveness of cells.

PMID- 16433854
TI  - Allergen-induced interleukin-9 production in vitro: correlation with atopy in
      human adults and comparison with interleukin-5 and interleukin-13.
AB  - BACKGROUND: The contribution of IL-9 to human atopy is supported by genetic
      studies. However, IL-9 production in response to allergen in vitro has been
      reported only in children. OBJECTIVE: Study IL-9 induction by allergen in adults,
      compare it with IL-5 and IL-13 and evaluate its association with atopy. METHODS:
      Peripheral blood mononuclear cell (PBMC) from control adults and from atopic
      patients were cultured with various allergens or phytohaemagglutinin (PHA) and
      secreted IL-5, IL-9 and IL-13 were measured by ELISA. RESULTS: IL-9 was produced
      in response to Dermatophagoides pteronyssinus (Der p) by PBMC from Der p
      hypersensitive adults at levels equivalent to those induced by PHA but with
      slower kinetics. The induction of IL-9 was allergen specific, reflecting donor
      RAST profile. In Der p-triggered reactions of non-atopic and atopic subjects, IL
      9 showed the highest selectivity for atopics, IL-5 and IL-13 being produced more
      frequently in non-atopic donors. Significant correlations with specific IgE
      titres were found for IL-9 with all allergens tested (Der p and two peptides of
      Bet v 1 birch allergen). For IL-5 and IL-13, they were in the same range for Der
      p but more variable for birch allergens. Patterns of cytokine production by
      individual patients in response to allergen reflected these differences: for Der
      p, IL-5, IL-9 and IL-13 productions were strongly correlated but for birch IL-5
      differed from the latter two. The in vitro production of IL-9 reflected clinical
      hypersensitivity profiles and was higher in individuals with asthma than in those
      with disease limited to rhinitis and/or conjunctivitis. CONCLUSIONS: Allergen
      triggered IL-9 production in vitro is an excellent marker for atopy in adults
      given its virtual absence in allergen-stimulated PBMC from non-atopic individuals
      and its correlation with allergen-specific IgE and asthma.

PMID- 16433856
TI  - Respiratory symptoms, bronchial hyper-responsiveness, and eosinophilic airway
      inflammation in patients with moderate-to-severe atopic dermatitis.
AB  - BACKGROUND: Patients with atopic dermatitis (AD) often have symptoms suggestive
      of asthma or rhinitis. The prevalence and signs of respiratory disease in AD
      patients have been studied to a limited extent. OBJECTIVES: To assess the
      prevalence and clustering of respiratory symptoms, bronchial hyper-responsiveness
      (BHR), and eosinophilic airway inflammation in patients with moderate-to-severe
      AD. METHODS: Eighty-six consecutive patients with moderate-to-severe AD and 49
      randomly selected control subjects without AD were studied by questionnaire, flow
      volume spirometry, histamine challenge to detect BHR, induced sputum test to
      detect eosinophilic airway inflammation, and skin prick tests (SPTs) and total
      serum immunoglobulin (Ig)E measurements to detect atopy. RESULTS: The patients
      with AD showed increased risk of physician-diagnosed asthma (36% vs. 2%, odds
      ratio (OR) 10.1, confidence interval (CI) 1.3-79.7, P=0.03), physician-diagnosed
      allergic rhinitis (AR) (45% vs. 6%, OR 4.5, CI 1.2-16.7, P=0.02), BHR (51% vs.
      10%, OR 5.5, CI 1.5-20.1, P=0.01), and sputum eosinophilia (81% vs. 11%, OR 76.1,
      CI 9.3-623.5, P<0.0001) compared with the control subjects. In AD patients,
      elevated s-IgE and positive SPTs were associated with the occurrence of physician
      diagnosed asthma and AR, BHR, and the presence of sputum eosinophilia.
      CONCLUSIONS: BHR and eosinophilic airway inflammation are more common in patients
      with AD than in control subjects. The highest prevalences were seen in patients
      with AD who were SPT positive and had high IgE levels. Longitudinal studies are
      needed to assess the outcome of patients with signs of airway disease, in order
      to identify those who need early initiation of asthma treatment.

PMID- 16433857
TI  - Recurrent childhood upper respiratory tract infections do not reduce the risk of
      adult atopic disease.
AB  - BACKGROUND: Children of large families and those attending day care are at
      increased risk of respiratory tract infections, which in turn may protect against
      the development of allergic disease. Longitudinal studies investigating these
      associations beyond childhood are, however, scarce. OBJECTIVE: To investigate the
      association between childhood recurrent upper respiratory tract infections (URTI)
      and asthma, allergic rhinitis (AR) and eczema in adulthood. METHODS: A birth
      cohort of 1055 members followed prospectively from the ages of 2 to 21 years.
      Detailed information on URTI between the ages of 2 and 4 years was collected at 3
      monthly intervals in a standardized interview. At the age of 8 years, a parental
      questionnaire regarding URTI between the ages of 4 and 8 years was used. The
      incidence of asthma and atopic disease at the age of 21 years was determined
      using a standardized questionnaire. RESULTS: Of the original cohort, 693 (66%)
      members completed the questionnaire. Children who experienced recurrent URTI
      before the age of 2 years, between the ages of 2-4 years and between ages of 4
      and 8 years were not less likely to have asthma at 21 years of age than children
      who did not experience recurrent URTI, relative risk (RR) 0.97 (95% confidence
      interval (CI) 0.65-1.46), RR 1.45 (CI 0.95-2.21) and RR 1.51 (CI 0.97-2.36),
      respectively. Neither were recurrent URTI associated with a decreased risk of AR,
      nor eczema at the age of 21 years. CONCLUSIONS: Recurrent URTI in childhood did
      not reduce the risk of atopic disease in young adulthood.

PMID- 16433855
TI  - Involvement of reduced sensitivity to Ca in beta-adrenergic action on airway
      smooth muscle.
AB  - BACKGROUND: It is well known that beta-adrenoceptor agonists (beta-agonists)
      cause relaxation in airway smooth muscle mediated by a reduction in the
      concentration of intracellular Ca2+ ([Ca2+](i)). However, little is currently
      known regarding whether reduced sensitization to Ca2+ is involved in the beta
      adrenergic relaxation. OBJECTIVE: This study was designed to determine the
      intracellular mechanisms underlying suppression of Ca2+ sensitization in beta
      adrenergic relaxation (Ca(2+)-independent relaxation by beta-agonists). Methods
      Isometric tension and [Ca2+](i) were simultaneously measured in fura-2-loaded
      strips isolated from guinea-pig tracheal smooth muscles. The relationships
      between tension and [Ca2+](i) were examined in the inhibitory action of
      isoprenaline (ISO) and other cAMP-related agents against methacholine-induced
      contraction. RESULTS: The concentration-inhibition curve for ISO against
      methacholine in tension was significantly dissociated from the curve for ISO in
      [Ca2+](i). In ISO-induced relaxation, a reduction in tension was significantly
      greater than that in [Ca2+](i.) This phenomenon was mimicked by other cAMP
      related agents: forskolin and dibutyryl-cAMP. In contrast, the inhibitory action
      of SKF-96365, a non-selective inhibitor of Ca(2+) channels, was associated with
      that in [Ca2+](i). In the presence of Rp-cAMPS, an inhibitor of protein kinase A
      (PKA), ISO caused an equivalent relaxation with less reduction in [Ca2+](i). The
      effects of ISO were not affected by Y-27632, an inhibitor of Rho-kinase, or by
      bisindolylmaleimide, an inhibitor of protein kinase C. ISO failed to inhibit
      contraction elicited by calyculin A, an inhibitor of myosin phosphatase.
      Conclusion beta-Adrenergic action antagonizes not only Ca2+ mobilization but also
      Ca2+ sensitization in methacholine-induced contraction. The cAMP/PKA-independent,
      G(s)-direct action is more potent in Ca(2+)-independent relaxation by beta
      agonists than the cAMP/PKA-dependent pathway. Moreover, myosin phosphatase is a
      fundamentally affected protein in the reduced response to Ca2+ mediated by beta
      agonist. Our results may provide evidence that this Ca2+ desensitization is a
      novel target for a reliever medication using rapid-acting beta-agonists in acute
      asthma management.

PMID- 16433858
TI  - Genome-wide linkage analysis of allergic rhinoconjunctivitis in a Swedish
      population.
AB  - BACKGROUND: Allergic rhinoconjunctivitis is a common complex disorder
      characterized by itching and irritation in the nose, bouts of sneezing, watery
      rhinorrhoea, nasal congestion and itchy eyes with tears and swelling. Like other
      atopic disorders such as allergic asthma and atopic dermatitis, the development
      involves complex interactions of genes and environmental factors. OBJECTIVE: The
      purpose of this study was to identify susceptibility loci for allergic
      rhinoconjunctivitis. METHODS: We conducted a genome-wide linkage analysis using a
      non-parametric, affected-relative-pair method. The 250 families used were
      collected originally for an atopic dermatitis linkage study. RESULTS: Three
      regions showed favour in evidence of linkage to allergic rhinoconjunctivitis:
      3q13 (D3S1278: logarithm of odds ratio (LOD)=1.64, P<0.003), 4q34-35 (D4S1652:
      LOD=1.49, P<0.005) and 18q12 (D18S535: LOD=1.94, P<0.002). In addition, four
      regions showed weaker evidence in favour of linkage: 6p22-24 (D6S1959: LOD=1.39,
      P<0.006), 9p11-q12 (D9S1118: LOD=1.15, P<0.02), 9q33.2-34.3 (D9S915: LOD=1.29,
      P<0.01) and 17q11.2 (D17S1294: LOD=1.13, P<0.02). In single-point analysis, one
      locus on chromosome 3 close to marker D3S1278 reaches the suggestive level
      (LOD=2.28, P<6 x 10(-4)) while one on chromosome 17 close to marker D17S921
      almost reaches this level (LOD=2.17, P<8 x 10(-4), Table 3). CONCLUSION: Our
      results support the linkage to allergic rhinoconjunctivitis on 3q13, 6p23-p24 and
      9q34.3 shown in previous investigations.

PMID- 16433860
TI  - Sequence variants of the secreted phosphoprotein 1 gene are associated with total
      serum immunoglobulin E levels in a Japanese population.
AB  - BACKGROUND: Secreted phosphoprotein 1 (SPP1) is a cytokine with pleiotrophic
      immunological activities, including activation of macrophage chemotaxis and T
      helper type 1 (Th1) immune responses. SPP1 gene polymorphisms have been shown to
      be associated with several immune inflammatory diseases including multiple
      sclerosis (MS), which is characterized by fewer allergic symptoms and lower
      numbers of allergen sensitizations. OBJECTIVE: The present study examined whether
      SPP1 gene polymorphisms are associated with total serum IgE levels, atopy and
      asthma in a Japanese population. METHODS: This case-control association analysis
      examined 611 subjects, including 268 subjects with asthma. We genotyped three
      promoter and two exon polymorphisms at SPP1: -1687A/G; -381T/C; -94 deletion/G;
      5891C/T; and 7052T/C. Results Association analyses of SPP1 polymorphisms showed
      that homozygosities for the 5891T allele (P=0.009) and 7052C allele (P=0.001)
      were significantly associated with increased levels of total IgE in non-asthmatic
      subjects. However, these variants were not associated with asthma and atopy.
      Interestingly, individuals carrying the 5891C allele, which is more prevalent in
      patients with MS in Japanese populations, displayed significantly lower levels of
      total serum IgE. Individuals homozygous for the 7052C allele, which is associated
      with development of systemic lupus erythematosus, displayed significantly higher
      total serum IgE levels. CONCLUSION: These findings suggest that genetic
      polymorphisms in SPP1 may play a role in controlling basal levels of total serum
      IgE, independent of atopy.

PMID- 16433859
TI  - The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic
      risk factor for atopic asthma. The SAPALDIA Cohort Study.
AB  - BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1
      (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have
      been associated with increased risk of atopy and asthma. OBJECTIVE: To examine
      the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the
      IL-18 gene with atopic asthma in a large, well-characterized and population-based
      study of adults. METHODS: Prospective cohort study design was used to collect
      interview and biological measurement data at two examination time-points 11 years
      apart. Multivariate logistic regression analysis was used to assess the
      association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18
      promotor variant (-137G/C) was associated with a markedly increased risk for the
      prevalence of physician-diagnosed asthma with concomitant skin reactivity to
      common allergens. Stratification of the asthma cases by skin reactivity to common
      allergens revealed an exclusive association of IL-18 -137 G-allele with an
      increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95%
      confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no
      according association with asthma and concomitant negative skin reactivity
      (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype
      and positive skin prick test was statistically significant (P=0.029). None of 74
      incident asthma cases with atopy at baseline exhibited the CC genotype.
      CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is
      an important genetic determinant involved in the development of atopic asthma.

PMID- 16433861
TI  - The diagnosis of Brazil nut allergy using history, skin prick tests, serum
      specific immunoglobulin E and food challenges.
AB  - BACKGROUND: Allergy to Brazil nut is a relatively common nut allergy and can be
      fatal. However, the evidence is lacking regarding the best approach to its
      diagnosis. OBJECTIVE: We sought to determine the relative merits of history, skin
      prick testing, measurement of serum-specific IgE and challenge in the diagnosis
      of Brazil nut allergy. METHODS: Fifty-six children and adults with a history of
      an allergic reaction to Brazil nut or evidence of sensitization were investigated
      by questionnaire (n=56), skin prick tests (SPTs) (n=53), measurement of serum
      specific IgE to Brazil nut (n=54) and double-blind, placebo-controlled labial,
      and if necessary oral, challenges (n=19). RESULTS: Brazil nut allergy occurred in
      highly atopic individuals of any age with a strong family history of atopy. In 24
      of 56 (43%), the history of an immediate reaction was sufficient to make a
      diagnosis with confidence and an oral challenge was considered unsafe. Of the 19
      subjects undertaking the 'gold standard' test of a double-blind, placebo
      controlled, food challenge, all six subjects with a SPT of at least 6 mm had a
      positive challenge and all three subjects with a SPT of 0 mm had a negative
      challenge. In the remaining 10 (53%) subjects, where SPT was between 1 and 5 mm
      and serum-specific IgE was less than 3.5 kU/L, an oral challenge was performed
      resulting in three positive and seven negative challenges. CONCLUSION: A
      combination of history, SPT and serum-specific IgE was adequate in achieving a
      diagnosis in the majority (77%) patients with suspected Brazil nut allergy.
      However, a doubtful history with SPT between 1 and 5 mm, or a serum-specific IgE
      less than 3.5 kU/L may require an oral challenge to help determine the risk of a
      Brazil nut allergic reaction.

PMID- 16433862
TI  - Influence of mattress characteristics on house dust mite allergen concentration.
AB  - BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is
      considered as a risk factor for HDM sensitization and development of asthma in
      genetically disposed people. Mattresses are one of the most important sources of
      HDMA in people's living environment. OBJECTIVE: The aim of this study was to
      evaluate the association between mattress characteristics and HDMA concentrations
      on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate
      the level of Der p 1 allergen. All participants filled in a questionnaire about
      the type of mattress, the type of covering (upper layer) of the mattress,
      dwelling characteristics and cleaning habits. Humidity and temperature of the
      bedroom were measured at the time of dust sampling. RESULTS: One hundred and
      sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress
      was associated with a higher level of Der p 1 compared with cotton upper layer
      (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was
      associated with significant higher concentrations and density of Der p 1.
      CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on
      mattresses, namely: a cotton upper layer of the mattress compared with a layer of
      synthetic material and lower RH at the time of sampling. As far as we know, the
      association between type of upper layer and concentration of Der p 1 has not been
      described before and could lead to the formulation of practical advices in order
      to reduce HDMA concentrations on mattresses.

PMID- 16433866
TI  - Drug safety and the media.
AB  - This article reviews the problems that may arise as a result of media coverage of
      drug safety issues. In order to promote more balanced coverage and avoid
      unnecessary scares, professionals working in the area of drug safety should
      rethink their strategies for dealing with the media.

PMID- 16433863
TI  - Evaluation of allergenicity of genetically modified soybean protein extract in a
      murine model of oral allergen-specific sensitization.
AB  - BACKGROUND: With the development of genetically modified crop plants there has
      been a growing interest in the approaches available to assess the potential
      allergenicity of novel gene products. For additional assessment of the potential
      allergenicity of expressed proteins, informative data can be generated using
      animal models. Soybean is one of the major source of protein in human and animal
      nutrition, and has also been well characterized as a major allergenic source.
      Advances in biotechnology have resulted in an increasing number of genetically
      engineered foods, and among these soybean is one of the most widespread.
      OBJECTIVE: To develop and characterize a murine model of IgE-mediated soybean
      sensitization induced by intragastric immunization, in the presence of Cholera
      Toxin, with wild-type soybean extract (wt-SE) or with genetically modified
      soybean extract (gm-SE). METHODS: Balb/c mice born in our animal facilities, from
      females fed on soy-free food, were fed with the same soy-free food and used in
      all the experiments. Mice were sensitized by gavages with soybean extracts, and
      allergen-specific IgE and IgG responses were studied by direct ELISA and ELISA
      inhibition. Antigen-specific cell proliferation and cytokine production were
      evaluated in spleen cell cultures. Results Sensitization with both soybean
      extracts induced high levels of antigen-specific IgE and IgG1 and low levels of
      specific IgG2a. Both wt-SE and gm-SE were able to inhibit the binding of specific
      IgE from mice immunized with gm-SE to the same antigen used for the ELISA
      coating. A comparable proliferative response was obtained with the homologous as
      well as with the heterologous extracts. CONCLUSION: In sensitized mice, we
      observed a predominantly T-helper type 2 (Th2)-type immune response, with
      increased soybean-specific IgE and IgG1 antibodies and a concomitant increase of
      IL-4 and IL-5 production. RESULTS: obtained by specific IgE ELISA inhibition and
      by antigen-specific T cell proliferation demonstrated that wt-SE and gm-SE shared
      B and T epitopes. The present murine model of soybean sensitization established
      by the oral route should provide valuable information about risk assessment for
      food allergy from new proteins of genetically modified foods.

PMID- 16433867
TI  - Comparative effects of ivabradine, a selective heart rate-lowering agent, and
      propranolol on systemic and cardiac haemodynamics at rest and during exercise.
AB  - AIM: To compare in humans the effects of ivabradine and propranolol on cardiac
      and systemic haemodynamics at rest, during tilt and exercise. METHODS: Nine
      healthy volunteers randomly received single oral doses of ivabradine (Iva, 30
      mg), propranolol (Propra, 40 mg) or placebo (Plac) during a double-blind cross
      over study. Doses were selected to be equipotent in heart rate (HR) reduction.
      HR, systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI,
      bioimpedance), rate pressure product (RPP), plasma epinephrine (E) and
      norepinephrine (NE), were measured at rest at baseline, before and after two tilt
      and exercise tests, started 2 and 5 h after drug intake. Heart rate variability
      (low to high frequency ratio LF/HF) was evaluated at rest and at 5 th minute of
      tilt. RESULTS: At rest, HR and RPP decreased similarly with Iva and Propra (both
      P < 0.01). During tilt, HR increased less with Iva than Propra (P < 0.01), LF/HF
      decreased after Iva (P < 0.03), SBP and mean blood pressure decreased after
      Propra (both P < 0.01), RPP decreased similarly after Iva and Propra (both P <
      0.01) and CI decreased to a greater extent with Propra than with Iva or Plac
      (both P < 0.04). During exercise, Iva and Propra similarly decreased HR (both P <
      0.01) and RPP (P < 0.01). CONCLUSIONS: These results demonstrate that for a
      similar decrease in HR at rest and during sympathetic stimulation, acute
      administration of ivabradine, a selective heart rate-lowering agent, decreased
      myocardial oxygen demand to the same extent as a reference beta-blocker,
      propranolol, but without evidence of depressant effect on cardiac function.

PMID- 16433868
TI  - A placebo-controlled study of retinal blood flow changes by pentoxifylline and
      metabolites in humans.
AB  - AIM: To investigate the possible effects of pentoxifylline metabolites on retinal
      blood flow in humans. METHODS: A randomized, placebo-controlled, four-period
      cross-over study that was observer blinded and partly blinded for the eight
      participants. On one occasion a placebo was given as an intravenous (i.v.)
      infusion over 100 min. On the other three occasions pentoxifylline was
      administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two
      of the pentoxifylline infusions the subjects were pretreated with either
      ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser
      doppler flowmetry (SLDF) in a selected area of the central temporal retina
      before, during and until 5 h after the end of infusion. Blood samples for
      concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken
      serially and areas under the curves (AUCs) were calculated. Linear mixed models
      were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were
      significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs.
      4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin.
      The mean AUC for M5 was significantly reduced when subjects were pretreated with
      rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with
      rifampicin significantly increased retinal blood flow assessed as mean flow,
      pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole),
      compared with placebo. The increases over placebo were more pronounced on
      diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6%
      (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after
      rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and
      5.1% (1.4, 7.8) over placebo, respectively. After co-administration of
      pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards
      increased flow during diastole, but a significant decrease in pulsation. When
      AUCs for pentoxifylline and its metabolites were used as regressor variables to
      retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with
      a positive sign indicating that they enhanced the retinal blood flow. In
      contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to
      decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The
      R-M1 and M5 metabolites of pentoxifylline contributed significantly to the
      effects of pentoxifylline on retinal blood flow.

PMID- 16433869
TI  - Interpatient variability in the pharmacokinetics of the HIV non-nucleoside
      reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6
      polymorphism.
AB  - AIMS: To characterize the demographic and pharmacogenetic factors that influence
      interpatient variability in the plasma concentrations of the HIV non-nucleoside
      reverse transcriptase inhibitor efavirenz. METHODS: Data from all samples
      analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed.
      Information on gender, age, body weight, height, race, hormonal contraceptive use
      (in a subset of patients), and time between sampling and last intake was
      recorded. PCR-restriction fragment length polymorphism analysis was performed to
      detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and
      CYP2B6*7) which is associated with low CYP2B6 activity. RESULTS: A total of 255
      patients were included in this analysis. The median plasma efavirenz
      concentration was 2.50 (interquartile range: 1.85-3.55) mg l(-1). Eight patients
      (3.1%) were considered to have a subtherapeutic plasma concentration (<1.0 mg l(
      1)) and 48 (18.9%) a toxic efavirenz concentration (>4.0 mg l(-1)). Gender, time
      after last intake, and race were the only factors that were significantly related
      to plasma efavirenz concentration in a multivariate analysis. No influence was
      observed for body weight, hormonal contraceptive use, and the presence of the
      CYP2B6 C1459T polymorphism. CONCLUSIONS: Gender and race are important factors in
      determining interpatient variability in plasma efavirenz concentrations which
      were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians
      should be particularly alert for signs of efavirenz-induced toxicity in females
      and non-Caucasian patients.

PMID- 16433870
TI  - Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and
      breast-feeding.
AB  - AIMS: To compare the disposition of fluoxetine and norfluoxetine enantiomers in
      the mother, foetus and infant. METHODS: Blood from pregnant women taking
      fluoxetine (n = 9), during pregnancy was sampled in the third trimester and at
      delivery (maternal and cord venous blood), and from the infants 48 h after
      delivery. The subset of these women who were breastfeeding, plus additional
      subjects recruited in the postpartum period, were studied further, and maternal
      and infant blood, and breast milk was sampled between 6 days and 11 months (n =
      23). Drug and metabolite concentrations were measured using gas
      chromatography/mass spectrometry or liquid chromatography, tandem mass
      spectrometry. RESULTS: There was a high correlation between maternal and foetal
      (cord blood) fluoxetine and norfluoxetine enantiomers (r(2)-0.9), the mean
      foetal/maternal ratios (95% confidence intervals) being 0.91 (0.61, 1.02) and
      1.04 (0.93, 1.05), for fluoxetine and norfluoxetine, respectively. In 2 day old
      infants exposed to the drug in utero, the fluoxetine and norfluoxetine plasma
      concentrations were the same as in cord blood at delivery. Over the next 2
      months, the plasma concentrations in the infants fell progressively.
      Stereoselective disposition of both the drug and metabolite in the mother,
      foetus, infant and breast milk was observed. The S : R ratios in the foetus and
      newborn ( approximately 3) were significantly higher than in the serum (
      approximately 2) or breast milk ( approximately 1.9) of the mothers, resulting in
      greater exposure of the foetus and infants to the biologically active
      enantiomers, particularly S-norfluoxetine. CONCLUSIONS: Foetal and infant
      exposure to fluoxetine and norfluoxetine is enhanced by their stereoselective
      disposition in the mother, foetus, breast milk and infant. Increased exposure may
      also result from decreased metabolism of the drug in the foetus and neonate.

PMID- 16433871
TI  - Population pharmacokinetic modelling of gentamicin and vancomycin in patients
      with unstable renal function following cardiothoracic surgery.
AB  - AIMS: To describe the population pharmacokinetics of gentamicin and vancomycin in
      cardiothoracic surgery patients with unstable renal function. METHODS: Data
      collected during routine care were analyzed using NONMEM. Linear relationships
      between creatinine clearance (CL(Cr)) and drug clearance (CL) were identified,
      and two approaches to modelling changing CL(Cr) were examined. The first included
      baseline (BCOV) and difference from baseline (DCOV) effects and the second
      allowed the influence of CL(Cr) to vary between individuals. Final model
      predictive performance was evaluated using independent data. The data sets were
      then combined and parameters re-estimated. RESULTS: Model building was performed
      using data from 96 (gentamicin) and 102 (vancomycin) patients, aged 17-87 years.
      CL(Cr) ranged from 9 to 172 ml min(-1) and changes varied from -76 to 58 ml min(
      1) (gentamicin) and -86 to 93 ml min(-1) (vancomycin). Inclusion of BCOV and DCOV
      improved the fit of the gentamicin data but had little effect on that for
      vancomycin. Inclusion of interindividual variability (IIV) in the influence of
      CL(cr) resulted in a poorly characterized model for gentamicin and had no effect
      on vancomycin modelling. No bias was seen in population compared with individual
      CL estimates in independent data from 39 (gentamicin) and 37 (vancomycin)
      patients. Mean (95% CI) differences were 4% (-3, 11%) and 2% (-2, 6%),
      respectively. Final estimates were: CL(Gent) (l h(-1)) = 2.81 x (1 + 0.015 x
      (BCOV(CLCr)-BCOV(CLCr Median)) + 0.0174 x DCOV(CLCr)); CL(Vanc) (l h(-1)) = 2.97
      x (1 + 0.0205 x (CL(Cr)-CL(Cr Median))). IIV in CL was 27% for both drugs.
      CONCLUSIONS: A parameter describing individual changes in CL(cr) with time
      improves population pharmacokinetic modelling of gentamicin but not vancomycin in
      clinically unstable patients.

PMID- 16433872
TI  - Pharmacokinetic-pharmacodynamic modelling of QT interval prolongation following
      citalopram overdoses.
AB  - AIMS: To develop a pharmacokinetic-pharmacodynamic model describing the time
      course of QT interval prolongation after citalopram overdose and to evaluate the
      effect of charcoal on the relative risk of developing abnormal QT and heart-rate
      combinations. METHODS: Plasma concentrations and electrocardiograph (ECG) data
      from 52 patients after 62 citalopram overdose events were analysed in WinBUGS
      using a Bayesian approach. The reported doses ranged from 20 to 1700 mg and on 17
      of the events a single dose of activated charcoal was administered. The developed
      pharmacokinetic-pharmacodynamic model was used for predicting the probability of
      having abnormal combinations of QT-RR, which was assumed to be related to an
      increased risk for torsade de pointes (TdP). RESULTS: The absolute QT interval
      was related to the observed heart rate with an estimated individual heart-rate
      correction factor [alpha = 0.36, between-subject coefficient of variation (CV) =
      29%]. The heart-rate corrected QT interval was linearly dependent on the
      predicted citalopram concentration (slope = 40 ms l mg(-1), between-subject CV =
      70%) in a hypothetical effect-compartment (half-life of effect-delay = 1.4 h).
      The heart-rate corrected QT was predicted to be higher in women than in men and
      to increase with age. Administration of activated charcoal resulted in a
      pronounced reduction of the QT prolongation and was shown to reduce the risk of
      having abnormal combinations of QT-RR by approximately 60% for citalopram doses
      above 600 mg. CONCLUSION: Citalopram caused a delayed lengthening of the QT
      interval. Administration of activated charcoal was shown to reduce the risk that
      the QT interval exceeds a previously defined threshold and therefore is expected
      to reduce the risk of TdP.

PMID- 16433873
TI  - The pharmacokinetic and pharmacodynamic consequences of the co-administration of
      lamotrigine and a combined oral contraceptive in healthy female subjects.
AB  - AIMS: To assess the pharmacokinetic and pharmacodynamic effects of co
      administration of a combined oral contraceptive (ethinyloestradiol plus
      levonorgestrel) and lamotrigine. METHODS: Over a period of 130 days, healthy
      female subjects took lamotrigine (titrated up to 300 mg day(-1)) and the combined
      oral contraceptive, either individually or as co-therapy. Plasma
      ethinyloestradiol and levonorgestrel concentrations were measured in the presence
      and absence of lamotrigine, and serum lamotrigine concentrations were measured in
      the presence and absence of the combined oral contraceptive. Serum concentrations
      of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone,
      oestradiol and sex hormone binding globulin were also determined. RESULTS: Of the
      22 enrolled subjects, 16 had evaluable pharmacokinetic data. The mean (90% CI)
      ratios of lamotrigine area under the concentration-time curve from 0 to 24 h
      (AUC(0,24 h)) and maximum observed concentration (C(max)) of lamotrigine when it
      was given with the combined oral contraceptive and during monotherapy were 0.48
      (0.44, 0.53) and 0.61 (0.57, 0.66), respectively. Ethinyloestradiol
      pharmacokinetics were unchanged by lamotrigine, the mean combined oral
      contraceptive + lamotrigine : combined oral contraceptive alone ratios (90% CI)
      of the AUC(0,24 h) and C(max) of levonorgestrel were 0.81 (0.76, 0.86) and 0.88
      (0.82, 0.93), respectively. FSH and LH concentrations were increased (by 4.7-fold
      and 3.4-fold, respectively) in the presence of lamotrigine, but the low serum
      progesterone concentrations suggested that suppression of ovulation was
      maintained. Intermenstrual bleeding was reported by 7/22 (32%) of subjects during
      co-administration of lamotrigine and combined oral contraceptive. CONCLUSIONS: A
      clinically relevant pharmacokinetic interaction was observed during co
      administration of a combined oral contraceptive and lamotrigine. A dosage
      adjustment for lamotrigine may need to be considered when these agents are co
      administered. A modest decrease in the plasma concentration of levonorgestrel was
      also observed but there was no corresponding hormonal evidence of ovulation.

PMID- 16433874
TI  - Pharmacokinetics of ruboxistaurin are significantly altered by rifampicin
      mediated CYP3A4 induction.
AB  - AIMS: The aim of this study was to evaluate the effect of rifampicin co
      administration on the pharmacokinetics of ruboxistaurin and its active
      metabolite, N-desmethyl ruboxistaurin and, in addition, to compare the changes in
      pharmacokinetics of ruboxistaurin and N-desmethyl ruboxistaurin with the urinary
      6beta-hydroxycortisol : cortisol ratio. Ruboxistaurin is a specific protein
      kinase-C beta inhibitor in clinical development for the treatment of diabetic
      microvascular complications. METHODS: This was a two-period, one-sequence study.
      Sixteen healthy male subjects completed both study periods. In period one, a
      single 64 mg oral dose of ruboxistaurin was administered. In period two, 600 mg
      rifampicin was administered daily for 9 days, during which another single 64 mg
      ruboxistaurin dose was administered on day 7. Blood samples were collected and
      assayed for ruboxistaurin and N-desmethyl ruboxistaurin. CYP3A4 induction was
      assessed by ratios of urinary 6beta-hydroxycortisol : cortisol (6beta-OHC : C)
      obtained via 24 h and morning-spot sampling techniques. Results Following
      repeated doses of rifampicin, both the mean C(max) and AUC(0,infinity) of
      ruboxistaurin were significantly reduced by approximately 95% (P < or = 0.001).
      For the metabolite, the mean C(max) decreased by 68% (P < or = 0.001), and
      AUC(0,infinity) decreased by 77% (P < or = 0.001). The t(max) values did not
      appear affected. The 6beta-OHC : C ratios from both 24 h and morning spot methods
      increased significantly, consistent with CYP3A4 induction. CONCLUSIONS: The
      effect of rifampicin co-administration on the exposure of ruboxistaurin is
      consistent with ruboxistaurin being a substrate of CYP3A4. Therefore, co
      administration with known CYP3A4 inducing agents (rifampicin, carbamazepine,
      phenobarbital, etc.) may decrease the concentrations of ruboxistaurin and N
      desmethyl-ruboxistaurin. In this study, 6beta OHC : C ratios substantially
      underestimated the impact of rifampicin on ruboxistaurin.

PMID- 16433876
TI  - Polypharmacy and falls in the middle age and elderly population.
AB  - AIM: Falls in the elderly are common and often serious. We studied the
      association between multiple drug use (polypharmacy) and falls in the elderly.
      METHODS: This was a population-based cross-sectional study, part of the Rotterdam
      Study. The participants were 6928 individuals aged > or = 55 years. The
      prevalence of falls in the previous year was assessed. Medication use was
      determined with an interviewer-administered questionnaire with verification of
      use. Polypharmacy was defined as the use of four or more drugs per day. RESULTS:
      The prevalence of falls strongly increased with age. Falls were more common in
      women than in men. Fall risk increased with increasing disability, presence of
      joint complaints, use of a walking aid and fracture history. The risk of falling
      increased significantly with the number of drugs used per day (P for trend <
      0.0001). After adjustment for a large number of comorbid conditions and
      disability, polypharmacy remained a significant risk factor for falling.
      Stratification for polypharmacy with or without at least one drug which is known
      to increase fall risk (notably CNS drugs and diuretics) disclosed that only
      polypharmacy with at least one risk drug was associated with an increased risk of
      falling. CONCLUSIONS: Fall risk is associated with the use of polypharmacy, but
      only when at least one established fall risk-increasing drug was part of the
      daily regimen.

PMID- 16433875
TI  - A pilot clinical trial comparing an acid-buffering formulation (ACIDFORM gel)
      with metronidazole gel for the treatment of symptomatic bacterial vaginosis.
AB  - AIM: To compare the effectiveness of an acid-buffering formulation gel (ACIDFORM)
      with metronidazole gel in the treatment of symptomatic bacterial vaginosis (BV).
      METHODS: After a confirmed diagnosis of BV according to the criteria established
      by Nugent and Amsel, 30 nonpregnant women were enrolled in a randomized, double
      blind clinical study. The women were randomly assigned to receive either 5 g
      ACIDFORM gel (n = 13) or 10% metronidazole gel (n = 17) intravaginally once daily
      for five consecutive days. Participants were evaluated in two follow-up visits (7
      12 days and 28-35 days after treatment). Therapeutic success was defined as the
      presence of less than three of Amsel's criteria. If three or more criteria were
      present at first or second follow-up visit, the woman was excluded from the study
      and treated orally with metronidazole. Nugent scores were recorded at each visit
      but these were not used to define cure. RESULTS: At the first follow-up visit, 15
      (88%) of the women in the metronidazole group were cured compared with only three
      (23%) in the ACIDFORM group (P < 0.001). The remaining 12 women (10 of the
      ACIDFORM group and two of the metronidazole group) were considered as failure and
      were treated orally with metronidazole. At the second follow-up visit, two of the
      ACIDFORM-treated women and six of the metronidazole-treated women presented
      recurrent BV. Four women in the ACIDFORM group and one in the metronidazole group
      reported occasional burning and itching during product use. CONCLUSION: ACIDFORM
      gel was significantly less effective than high-dose metronidazole gel for the
      treatment of symptomatic BV.

PMID- 16433877
TI  - Did intense adverse media publicity impact on prescribing of paroxetine and the
      notification of suspected adverse drug reactions? Analysis of routine databases,
      2001-2004.
AB  - AIM: To document the impact on clinical practice in England of media attention
      around possible adverse effects of paroxetine. DESIGN: Analysis of national
      selective serotonin reuptake inhibitor (SSRI) prescribing trends and yellow-card
      adverse drug reaction reports, 2001-2004. RESULTS: From a steady state in 2001,
      paroxetine prescribing declined sharply from April 2002, coinciding with a USA
      regulatory action; the subsequent decline in paroxetine prescribing was 1.87% per
      month (95% confidence interval - 2.06, -1.68). Other SSRI prescribing increased
      by 1% per month until a major UK review of SSRIs in children in December 2003,
      after which prescribing plateaued. Media publicity was associated with short-term
      peaks in yellow-card reports related to paroxetine. CONCLUSION: Falls in
      paroxetine and other SSRI prescribing in the UK coincided, respectively, with
      regulatory communications from the USA and the UK, but associations may have
      noncausal or other explanations. Reports of adverse reactions to paroxetine
      appeared to increase after adverse media publicity about the drug.

PMID- 16433879
TI  - Comparison of hospital episodes with 'drug-induced' disorders and spontaneously
      reported adverse drug reactions.
AB  - AIMS: To compare Hospital Episode Statistics for 'drug-related' admissions with
      spontaneously reported adverse drug reactions (ADRs) using UK Yellow Card data
      for the period 1996-2000. METHODS: This was a descriptive study for which we
      matched the relevant datasets in respect of time, place, evidence of
      hospitalization and disease terminology. The principal outcome was the ratio of
      ADRs leading to hospitalization which had been reported spontaneously during the
      whole study period. RESULTS: Twenty types of ADR were included and between them
      there was a wide spread of overall ratios (range 0-130%). The general tendency
      was for under-reporting on Yellow Cards but for ADRs with a fatal outcome this
      appeared to be less (range 7-168%). CONCLUSIONS: This study provides some broad
      indications of the degree of under-reporting of ADRs that occurs despite a
      clinical diagnosis of a serious ADR being made and recorded.

PMID- 16433878
TI  - Warfarin use and the risk of motor vehicle crash in older drivers.
AB  - AIM: On the basis of a recent report, we assessed whether the use of warfarin by
      elderly drivers results in an increased risk of motor vehicle crash. METHODS: We
      used computerized records of Quebec insurance programmes, covering a population
      of 7 million people, to conduct a case-control study based on 5,579 cases and
      12,911 controls. RESULTS: The rate of injurious motor vehicle crash associated
      with the use of warfarin in the past year was not elevated (rate ratio 0.74; 95%
      confidence interval 0.55, 1.05). CONCLUSIONS: Warfarin therapy does not appear to
      increase the risk of motor vehicle accidents in elderly drivers.

PMID- 16433880
TI  - Application of a newly designed electronic monitoring device for press through
      packaging sheets in a clinical trial.

PMID- 16433882
TI  - Adverse drug reactions to NSAIDs.

PMID- 16433885
TI  - Assessment of the risk of iatrogenic hypergastrinaemia from patients with
      gastrinoma.

PMID- 16433886
TI  - Consequences of long-term proton pump blockade: insights from studies of patients
      with gastrinomas.
AB  - Proton pump inhibitors are being increasingly used and for longer periods of
      time, especially in patients with gastroesophageal reflux disease. Each of these
      trends has led to numerous studies and reviews of the potential risk-benefit
      ratio of the long-term use of proton pump inhibitors. Both long-term effects of
      hypergastrinaemia due to the profound acid suppression caused by proton pump
      inhibitors as well as the effects of hypo-/achlorhydria per se have been raised
      and studied. Potential areas of concern that have been raised in the long-term
      use of proton pump inhibitors, which could alter this risk-benefit ratio include:
      gastric carcinoid formation; the development of rebound acid hypersecretion when
      proton pump inhibitor treatment is stopped; the development of tolerance;
      increased oxyntic gastritis in H. pylori patients and the possibility of
      increasing the risk of gastric cancer; the possible stimulation of growth of non
      gastric tumours due to hypergastrinaemia; and the possible effect of the
      hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12.
      Because few patients with idiopathic gastro-oesophageal reflux disease/peptic
      ulcer disease have been treated long-term (i.e., >10 years), there is little
      known to address the above areas of potential concern. Most patients with
      gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia,
      require continuous proton pump inhibitors treatment and a number of studies
      report results of >5-10 years of tratment and follow-up. Therefore, an analysis
      of Zollinger-Ellison syndrome patients can provide important insights into some
      of the safety concerns raised above. In this paper, results from studies of
      Zollinger-Ellison syndrome patients and other recent studies dealing with the
      safety concerns above, are briefly reviewed.

PMID- 16433887
TI  - Therapeutic drug monitoring and human immunodeficiency virus (HIV) antiretroviral
      therapy.
AB  - Treatment with antiretroviral drugs such as the HIV protease inhibitors and non
      nucleoside reverse transcriptase inhibitors have contributed to the improvement
      of life of many HIV-infected patients in recent years, but antiretroviral therapy
      is not without problems. In some patients, treatment is not effective and
      suppression of viral replication is not achieved. Other patients experience
      toxicity and have to stop treatment or change to a less effective treatment.
      Several studies have demonstrated a relationship between plasma concentrations of
      the protease inhibitors and non-nucleoside reverse transcriptase inhibitors and
      viral suppression and toxicity. Therapeutic drug monitoring uses drug
      concentrations to individualize and optimise therapy by dosage adjustments and
      many clinicians have advocated for the use of therapeutic drug monitoring in HIV
      antiretroviral therapy. Evidence from a number of randomized clinical trials
      supports the use of therapeutic drug monitoring, but the studies have limitations
      and might not apply to all the antiretroviral drugs. However, the consensus is
      that certain patients are very likely to benefit from therapeutic drug
      monitoring. Additionally, the combination of therapeutic drug monitoring and
      genotypic or phenotypic resistance testing might further improve antiretroviral
      therapy.

PMID- 16433888
TI  - Protection by turmeric and myrrh against liver oxidative damage and genotoxicity
      induced by lead acetate in mice.
AB  - The effects of lead acetate in the diet (0.5% w/w) on reduced GSH, activity of
      phase II metabolizing enzyme glutathione S-transferase (GST), lipid peroxidation
      in liver homogenate and bone marrow chromosomes of mice simultaneously
      supplemented with powdered turmeric and myrrh for 8 weeks were investigated. Five
      groups of Swiss male albino mice, each of 30 mice, the first group received a
      basal diet and served as negative control, the second group received basal diet
      supplemented with lead acetate only and served as positive control. The other
      three groups received basal diet supplemented with lead acetate and 1% or 5%
      turmeric powder and 1% myrrh powder, respectively. Results revealed a significant
      decrease in the amount of GSH in all treated groups compared with negative
      control. Also, the activity of GSH S-transferase was significantly decreased in
      positive control compared with other groups. However, co-administration of the
      protective plants resulted in a significant increase in the activity of GST
      compared with both positive and negative control groups. Furthermore, lipid
      peroxidation was significantly increased in positive control alone, while co
      treatment with the protective plants resulted in reduction in the level of lipid
      peroxidation by 31% and 49% in mice receiving 1% and 5% turmeric powder
      respectively and 45% in 1% myrrh treated when compared with their respective
      positive control group. Lead genotoxicity was confirmed through significant
      reduction in the number of dividing cells, increased total number of aberrant
      cells and increased frequency of chromosomal aberrations. Simultaneous treatment
      with these plants significantly reduced the genotoxicity induced by lead
      administration and the powerful protection was observed with 5% powdered
      turmeric. It may be concluded that turmeric and myrrh are useful herbal remedies,
      especially for controlling oxidative damages and genotoxicity induced by lead
      acetate intoxication.

PMID- 16433889
TI  - Arsenic-induced cell death in liver and brain of experimental rats.
AB  - Arsenic is a well established human carcinogen and is ubiquitous in the
      environment. The present study demonstrates the effect of acute arsenic
      administration at three different doses in liver and brain of Wistar rats. Sodium
      arsenite was administered orally at doses of 6.3 mg/kg, 10.5 mg/kg and 12.6 mg/kg
      of body weight on the basis of a lethal dose 50% (LD50) for 24 hr. After
      administration of arsenites, liver and brain were analyzed for various parameters
      of oxidative stress, histopathological changes and caspase-3 activity.
      Glutathione levels were decreased significantly in the liver at all doses. In
      liver the following biochemical changes were observed, a significant lipid
      peroxidation and cytochrome-P450 induction along with significant decrease in
      catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The
      activity of glutathione peroxidase was increased significantly at all doses. In
      brain, no significant change was observed at 6.3 mg/kg. However, a significant
      increase in lipid peroxidation and glutathione peroxidase activity along with
      significant decrease in the activity of glutathione, catalase and superoxide
      dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione
      S-transferase was decreased significantly in both liver and brain at 10.5 and
      12.6 mg/kg. No significant alteration in the activity of glucose-6-phosphate
      dehydrogenase and glutathione reductase was observed in either liver or brain at
      any dose. Dose-dependent histopathological changes, observed in both liver and
      brain are also described. A significant increase in caspase-3 activity was
      observed at all doses in liver and at 10.5 and 12.6 mg/kg in brain. Sodium
      arsenite caused DNA cleavage into fragments and manifested as "DNA laddering", a
      hallmark of apoptosis.

PMID- 16433891
TI  - Muscle symptoms associated with statins: a series of twenty patients.
AB  - The aim of this study was to examine the clinical profile of statin-induced
      myalgia in patients with no apparent predisposing factors. Patients who reported
      muscle complaints that limited daily functioning during statin use were
      prospectively identified among the patients of Kuusankoski District Hospital and
      its catchment area, a population of about 100,000, between January 2003 and July
      2004. Twenty patients in whom the muscle complaints were probably attributable to
      the use of a statin were included in this series. There were no cases of severe
      myopathy or rhabdomyolysis, and the highest creatine kinase value observed was
      only about 1900 U/l. Of the 18 patients that were evaluable for creatine kinase
      level, 5 (28%) did not exhibit elevation of creatine kinase and 6 (33%) showed a
      minor increase only. Following discontinuation of the statin, resolution of
      symptoms and normalisation of creatine kinase occurred in 11 of the 13 patients
      with elevated creatine kinase value as well as muscle complaints. Statins may
      cause clinically important muscle symptoms without inducing a marked creatine
      kinase elevation.

PMID- 16433890
TI  - Trimidox induces apoptosis via cytochrome c release in NALM-6 human B cell
      leukaemia cells.
AB  - Trimidox (3,4,5-trihydroxybenzamidoxime) has been shown to reduce the activity of
      ribonucleotide reductase accompanied by growth inhibition and the differentiation
      of mammalian cells. Here we examine the induction of apoptosis by trimidox in
      several human leukaemia cell lines, focusing on the release of cytochrome c and
      the activation of caspase proteases in the human B cell line NALM-6. Induction of
      apoptosis by trimidox (300 microM) was detected in NALM-6, HL-60 (premyelocytic
      leukaemia cells), MOLT-4 (an acute lymphoblastic leukaemia cells), Jurkat (a T
      cell leukaemia cells), U937 (expressing many monocyte-like characteristics), and
      K562 (erythroleukaemia). NALM-6 was most affected by trimidox among leukaemia
      cells; therefore, we employed NALM-6 cells in the subsequent experiments. The
      cells showed a time-dependent increase in DNA damage after trimidox (250 microM)
      treatment. A significant increase in the amount of cytochrome c release was
      detected after treatment with trimidox. Bcl-2 and Bax protein expressions were
      not changed by trimidox. Caspase-3 and -9 were activated by incubation with
      trimidox, whereas caspase-8 was not. Furthermore, trimidox-induced apoptosis was
      prevented by a broad-spectrum caspase inhibitor, a caspase-3, and a caspase-9
      inhibitor, but not by a caspase-8 inhibitor. Inhibition of c-Jun NH2-terminal
      kinase (JNK) by SP600125 appreciably protected cells from trimidox-induced
      apoptosis, but no effect inhibition of p38 mitogen-activated protein kinase
      (MAPK) by SB203580. In contrast, extracellular signal-regulated kinase (ERK)
      inhibitors U0126 and PD98059 strongly potentiated the apoptotic effect of
      trimidox. This report shows that the induction of apoptosis by trimidox occurs
      through a cytochrome c-dependent pathway, which sequentially activates caspase-3
      and caspase-9.

PMID- 16433892
TI  - Effects of Coeloglossum. viride var. bracteatum extract on memory deficits and
      pathological changes in senescent mice.
AB  - Previous studies have shown that injection of D-galactose could result in
      senescent performances in animals, that injection of NaNO2 could cause ischaemia
      and hypoxia in many organs, and combined injection of D-galactose and NaNO2 make
      normal mice taking on senescent performances in a shorter period. The aim of this
      study was to investigate the effects of CE, an extract from a Tibetan medicinal
      herb, Coeloglossum. viride (L.) Hartm. var. bracteatum (Willd.), on senescent
      mice. The step-down test was performed to evaluate the learning and memory
      function of mice. The activities of superoxide dismutase, adenosine
      triphosphatase, monoamine oxydase and the content of malondialdehyde were
      measured to determine the impairment of brain. The expressions of Bcl-2, Bax, and
      caspase-3 proteins in mouse hippocampus were studied by immunohistochemical
      staining. The data demonstrated that D-galactose and NaNO2 treated mice had
      significant deficits in learning and memory function. The reduced activities of
      superoxide dismutase, adenosine triphosphatase, increased activities of monoamine
      oxydase and level of malondialdehyde were also found. Bax and caspase-3 positive
      cells increased while Bcl-2 positive cells decreased remarkably. Treatment of CE
      (2.5, 5 mg.kg(-1)) ameliorated the memory impairment; rectified the biochemistry
      and neural system changes in mice. These results suggest that CE offers promise
      as a tool for treatment of senescence-related diseases.

PMID- 16433893
TI  - Up-regulation of alpha1A-adrenoceptors in rat mesenteric artery involves
      intracellular signal pathways.
AB  - The aim of the present study was to investigate if there is an altered expression
      of alpha-adrenoceptors during organ culture of rat mesenteric artery segments by
      using a sensitive pharmacological method and molecular biological techniques.
      Noradrenalin (NA) induced contraction via alpha1-adrenoceptors. The contraction
      and alpha1A-adrenoceptor mRNA levels were elevated during organ culture.
      Transcriptional inhibitor actinomycin D, translational inhibitor cycloheximide,
      protein kinase C inhibitors (staurosporine and RO31-8220) and mitogen-activated
      protein kinase (MAPK) pathway inhibitors (SB386023, U0126 and SB239063) prevented
      the increase in NA-induced contractions. The amount of alpha1A-adrenoceptor mRNA
      was significantly lower in the artery segments cultured for 1 day in the presence
      of specific MAPK extracellular signal-regulated protein kinase1/2 pathway
      inhibitor SB386023 than that of the cultured controls. SB386023 did not affect
      alpha2-adrenoceptor mRNA level. Our results suggest that the up-regulation of
      alpha1A-adrenoceptors involves transcription and intracellular signal
      transduction via the protein kinase C and the ERK 1/2 pathways.

PMID- 16433894
TI  - Alpha-tocopherol and alpha-lipoic acid enhance the erythrocyte antioxidant
      defence in cyclosporine A-treated rats.
AB  - The aim of this study was to determine the effects of dietary antioxidant
      supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine A
      (cyclosporine)-induced alterations to erythrocyte and plasma redox balance. Rats
      were randomly assigned to either control, antioxidant (alpha-tocopherol 1000
      IU/kg diet and alpha-lipoic acid 1.6 g/kg diet), cyclosporine (25 mg/kg/day), or
      cyclosporine + antioxidant treatments. Cyclosporine was administered for 7 days
      after an 8 week feeding period. Plasma was analysed for alpha-tocopherol, total
      antioxidant capacity, malondialdehyde, and creatinine. Erythrocytes were analysed
      for glutathione, methaemoglobin, superoxide dismutase, catalase, glutathione
      peroxidase, glucose-6-phosphate dehydrogenase, alpha-tocopherol and
      malondialdehye. Cyclosporine administration caused a significant decrease in
      superoxide dismutase activity (P<0.05 control versus cyclosporine) and this was
      improved by antioxidant supplementation (P<0.05 cyclosporine versus cyclosporine
      + antioxidant; P<0.05 control versus cyclosporine + antioxidant). Animals
      receiving cyclosporine and antioxidants showed significantly increased (P<0.05)
      catalase activity compared to both groups not receiving cyclosporine.
      Cyclosporine administration induced significant increases in plasma
      malondialdehyde and creatinine concentration (P<0.05 control versus
      cyclosporine). Antioxidant supplementation prevented the cyclosporine induced
      increase in plasma creatinine (P<0.05 cyclosporine versus cyclosporine +
      antioxidant; P>0.05 control versus cyclosporine + antioxidant), however,
      supplementation did not alter the cyclosporine induced increase in plasma
      malondialdehyde concentration (P>0.05 cyclosporine versus cyclosporine +
      antioxidant). Antioxidant supplementation resulted in significant increases
      (P<0.05) in plasma and erythrocyte alpha-tocopherol in both of the supplemented
      groups compared to non-supplemented groups. In conclusion, dietary
      supplementation with alpha-tocopherol and alpha-lipoic acid enhanced the
      erythrocyte antioxidant defence and reduced nephrotoxicity in cyclosporine
      treated animals.

PMID- 16433895
TI  - Positive inotropic effect of levosimendan is correlated to its stereoselective
      Ca2+-sensitizing effect but not to stereoselective phosphodiesterase inhibition.
AB  - In order to clarify the mechanisms of the positive inotropic actions of
      levosimendan and its optical isomer, dextrosimendan, we compared their
      concentration-dependent effects in intact papillary muscles, permeabilized
      cardiomyocytes and in purified phosphodiesterase enzyme preparations of guinea
      pig hearts. In papillary muscles twitch tension increased with EC50 values of 60
      nM and 2.8 microM for levosimendan and dextrosimendan, respectively. Hence, the
      two enantiomers exhibited a 47 times potency difference in their positive
      inotropic effects in a preparation where theoretically Ca2+-sensitization and
      phosphodiesterase inhibition could both contribute to the positive inotropic
      effects. In guinea-pig cardiomyocytes, levosimendan and dextrosimendan increased
      isometric force production (at pCa 6.2) due to Ca2+-sensitization with EC50
      values of 8.4 nM and 0.64 microM, respectively, with a similar relative potency
      difference of 76. A major difference appeared in their relative pharmacological
      potencies, however, when the inhibitory effects of the two enantiomers were
      assayed on phosphodiesterase III, purified from guinea pig left ventricle (i.e.
      the phosphodiesterase isoenzyme which is dominant in that tissue). Levosimendan
      was a 427 times more potent phosphodiesterase inhibitor than dextrosimendan, with
      IC50 values of 7.5 nM, and 3.2 microM, respectively. Taken together, our data
      support the hypothesis that levosimendan and dextrosimendan exert their positive
      inotropic effects via a stereoselective Ca2+-sensitizing mechanism and not via
      stereoselective inhibition of phosphodiesterase III in the myocardium.

PMID- 16433896
TI  - Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human
      immunodeficiency virus (HIV) protease inhibitors in vitro.
AB  - The effects of five HIV protease inhibitors (amprenavir, indinavir, nelfinavir,
      ritonavir and saquinavir) on cytochrome P450 (CYP) 3A4, 3A5 and 3A7 activities
      were studied in vitro using testosterone 6beta-hydroxylation in recombinant
      CYP3A4, CYP3A5 and CYP3A7 enzymes. The protease inhibitors showed differential
      inhibitory effects on the three CYP3A forms. Ritonavir and saquinavir were non
      selective and preferential inhibitors of CYP3A4 and CYP3A5 (K(i) 0.03 microM and
      0.6-0.8 microM for ritonavir and saquinavir, respectively), and weaker inhibitors
      of CYP3A7 (K(i) 0.6 microM and 1.8 microM, respectively). Nelfinavir was a potent
      and non-selective inhibitor of all three CYP3A forms (K(i) 0.3-0.4 microM).
      Amprenavir and indinavir preferentially inhibited CYP3A4 (K(i) 0.1 microM and 0.2
      microM, respectively), with weaker inhibitory effects on CYP3A5 (K(i) 0.5 microM
      and 2.2 microM, respectively) and CYP3A7 (K(i) 2.1 microM and 10.6 microM,
      respectively). In conclusion, significant differences exist in the inhibitory
      potency of protease inhibitors for different CYP3A forms. Ritonavir, nelfinavir,
      saquinavir and amprenavir seem to be prone to drug-drug interactions by
      inhibiting both CYP3A4 and CYP3A5. Especially nelfinavir and ritonavir also have
      a potential to inhibit foetal CYP3A7-mediated drug metabolism and some endogenous
      pathways that may be crucial to normal foetal development, while indinavir has
      the lowest potential to inhibit CYP3A5 and CYP3A7.

PMID- 16433897
TI  - Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared
      heroin, by intravenous or by inhalation route in opioid-dependent patients.
AB  - A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent
      patients in the Netherlands, who were currently treated with high doses of
      pharmaceutically prepared heroin on medical prescription. Besides intravenous
      heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In
      this technique, heroin base is heated on aluminium foil, and heroin vapours are
      inhaled into the lungs. Not much is known about the pharmacokinetics profile and
      bioavailability of this specific administration method. Therefore, a study was
      performed on pharmacokinetics and pharmacodynamics of heroin inhalation and
      intravenous use. Eleven patients who injected heroin and 9 patients who inhaled
      heroin entered the study. They were on steady-state heroin treatment for at least
      12 months. For safety reasons, there was no crossing-over between heroin
      injection or inhalation. In a double-blind randomised study, 67-100-150% of the
      regular heroin maintenance dose was administered to each patient. Maximal single
      heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6
      monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS
      MS. Blood pressure, heart rate, skin temperature and reaction time were assessed.
      Furthermore, visual analogue scales regarding craving and appreciation of heroin
      effect were scored by the subjects. Both in inhaling and injecting patients, the
      areas under curve of heroin and all measured metabolites were linearly related to
      heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after
      inhalation, than after intravenous injection. Bioavailability (F) of heroin
      inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from
      plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous
      administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl
      and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels
      were inversely related to creatinine clearance. After heroin administration, the
      reaction time was significantly prolonged with 28+/-5.3 msec. in injecting and
      13+/-4.9 msec. in inhaling patients. Cardiovascular changes were only mild after
      heroin administration. Craving-scores declined immediately after heroin
      administration in both administration groups. Subjective heroin effect was rated
      more positively in heroin inhaling than in injecting patients, despite the lower
      C(max) levels following heroin inhalation. In both groups, in this blinded study
      heroin dose increments were more appreciated than dose reductions. Increments of
      50% of the regular heroin dose did not cause any serious side effect.

PMID- 16433898
TI  - Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in
      streptozotocin-induced diabetic wistar rats.
AB  - Flavonoids are non-nutritive dietary components that are widely distributed in
      plants. The present study investigated the antihyperglycaemic and antioxidant
      effect of rutin, a polyphenolic flavonoid in normal and streptozotocin-induced
      diabetic Wistar rats. Diabetes as induced in rats by an intraperitoneal injection
      of streptozotocin. Rutin was orally administered to normal and diabetic rats for
      a period of 45 days. Fasting plasma glucose, glycosylated haemoglobin,
      thiobarbituric acid reactive substances and lipid hydroperoxides were
      significantly (P<0.05) increased, whereas insulin, C-peptide, total haemoglobin,
      protein levels, non-enzymic antioxidants (glutathione, vitamin C, vitamin E and
      ceruloplasmin) were decreased significantly (P<0.05) in diabetic rats. Oral
      administration of rutin to diabetic rats significantly (P<0.05) decreased fasting
      plasma glucose, glycosylated haemoglobin and increased insulin, C-peptide,
      haemoglobin and protein levels. Administration of rutin also decreased
      thiobarbituric acid reactive substances and lipid hydroperoxides and increased
      the non-enzymic antioxidants significantly (P<0.05). Treatment of normal rats
      with rutin did not significantly (P<0.05) alter any of the parameters studied.
      These results show that rutin exhibits antihyperglycaemic and antioxidant
      activity in streptozotocin-induced diabetic rats.

PMID- 16433899
TI  - Increasing Intracellular calcium of guinea pig ventricular myocytes induced by
      platelet activating factor through IP3 pathway.
AB  - We used Fluo-3/AM to examine the effect of platelet-activating factor on the
      intracellular Ca2+([Ca2+]i) levels in isolated myocytes of guinea pig ventricle.
      Myocytes were isolated with Langendorff perfusion technique and were challenged
      with platelet-activating factor. Addition of platelet-activating factor (1 pM to
      10 nM) significantly increased the [Ca2+]i in the presence and absence of
      extracellular Ca2+. The notion that increases in intracellular Ca2+ induced by
      platelet-activating factor is the result of stimulation of intracellular Ca2+
      pool rather than increasing Ca2+ influx was further supported by the whole cell
      patch-clamp experiments in which the platelet-activating factor did not alter the
      activity of L-type of Ca2+ channels (I(Ca-L)). Treatment of myocytes with
      ryanodine failed to abolish the stimulatory effect of platelet-activating factor
      on [Ca2+]i. In contrast, inhibition of IP3-sensitive Ca2+ release pool with 2
      aminoethoxydiphenyl borate (2-APB) blocked the effect of platelet-activating
      factor. We conclude that the platelet-activating factor-induced increase in
      intracellular Ca2+ is mediated by stimulation of IP3 receptor but not by
      stimulation of I(Ca-L) and ryanodine-sensitive receptor.

PMID- 16433900
TI  - Contribution of glucuronidation to tramadol disposition in early neonatal life.

PMID- 16433902
TI  - Detection of human MCP-4/CCL13 isoforms by SELDI immunoaffinity capture.
AB  - Monocyte Chemoattractant Proteins 4 (MCP-4/CCL13) is a member of a distinct,
      structurally-related subclass of CC chemokines mainly involved in recruitment of
      eosinphils to inflammatory sites. Recent evidence demonstrates that serum level
      of this protein strongly increases following high dose IL-2 immunotherapy. The
      physiological form of human MCP-4/CCL13 has yet to be purified. Therefore, the
      primary structure of the biologically relevant (mature) form has not been
      established. By using SELDI immunoaffinity capture technology we describe two
      mature isoforms both present in serum before and after high-dose IL-2
      immunotherapy.

PMID- 16433901
TI  - Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D
      FISH: MLL translocation revisited.
AB  - BACKGROUND: Haematological cancer is characterised by chromosomal translocation
      (e.g. MLL translocation in acute leukaemia) and two models have been proposed to
      explain the origins of recurrent reciprocal translocation. The first, established
      from pairs of translocated genes (such as BCR and ABL), considers the spatial
      proximity of loci in interphase nuclei (static "contact first" model). The second
      model is based on the dynamics of double strand break ends during repair
      processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23
      translocation has more than 40 partners, the study of the relative positions of
      the MLL gene with both the most frequent partner gene (AF4) and a less frequent
      partner gene (ENL), should elucidate the MLL translocation mechanism. METHODS:
      Using triple labeling 3D FISH experiments, we have determined the relative
      positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human
      cell lines. RESULTS: In all cell lines, the ENL gene is significantly closer to
      the MLL gene than the AF4 gene (with P value < 0.0001). According to the static
      "contact first" model of the translocation mechanism, a minimal distance between
      loci would indicate a greater probability of the occurrence of
      t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in
      contradiction to the epidemiology of 11q23 translocation. CONCLUSION: The
      simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing
      the correlation between spatial proximity and occurrence of translocation. Our
      observations are not consistent with the static "contact first" model of
      translocation. The recently proposed dynamic "breakage first" model offers an
      attractive alternative explanation.

PMID- 16433903
TI  - Disaggregation and invasion of ovarian carcinoma ascites spheroids.
AB  - BACKGROUND: Malignant ascites often develops in advanced stages of ovarian
      carcinoma, consisting of single and aggregated tumor cells, or spheroids.
      Spheroids have commonly been used as tumor models to study drug efficacy, and
      have shown resistance to some chemotherapies and radiation. However, little is
      known about the adhesive or invasive capabilities of spheroids, and whether this
      particular cellular component of the ascites can contribute to dissemination of
      ovarian cancer. Here, we examined the invasive ability of ascites spheroids
      recovered from seven ovarian carcinoma patients and one primary peritoneal
      carcinoma (PPC) patient. METHODS: Ascites spheroids were isolated from patients,
      purified, and immunohistochemical analyses were performed by a pathologist to
      confirm diagnosis. In vitro assays were designed to quantify spheroid
      disaggregation on a variety of extracellular matrices and dissemination on and
      invasion into normal human mesothelial cell monolayers. Cell proliferation and
      viability were determined in each assay, and statistical significance
      demonstrated by the student's t-test. RESULTS: Spheroids from all of the
      patients' ascites samples disaggregated on extracellular matrix components, with
      the PPC spheroids capable of complete disaggregation on type I collagen.
      Additionally, all of the ascites spheroid samples adhered to and disaggregated on
      live human mesothelial cell monolayers, typically without invading them. However,
      the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample
      occasionally formed invasive foci in the mesothelial cell monolayers, suggestive
      of a more invasive phenotype. CONCLUSION: We present here in vitro assays using
      ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results
      suggest that systematic studies of the ascites cellular content are necessary to
      understand the biology of ovarian carcinoma.

PMID- 16433905
TI  - Protocol of the COSMIN study: COnsensus-based Standards for the selection of
      health Measurement INstruments.
AB  - BACKGROUND: Choosing an adequate measurement instrument depends on the proposed
      use of the instrument, the concept to be measured, the measurement properties
      (e.g. internal consistency, reproducibility, content and construct validity,
      responsiveness, and interpretability), the requirements, the burden for subjects,
      and costs of the available instruments. As far as measurement properties are
      concerned, there are no sufficiently specific standards for the evaluation of
      measurement properties of instruments to measure health status, and also no
      explicit criteria for what constitutes good measurement properties. In this paper
      we describe the protocol for the COSMIN study, the objective of which is to
      develop a checklist that contains COnsensus-based Standards for the selection of
      health Measurement INstruments, including explicit criteria for satisfying these
      standards. We will focus on evaluative health related patient-reported outcomes
      (HR-PROs), i.e. patient-reported health measurement instruments used in a
      longitudinal design as an outcome measure, excluding health care related PROs,
      such as satisfaction with care or adherence. The COSMIN standards will be made
      available in the form of an easily applicable checklist. METHOD: An international
      Delphi study will be performed to reach consensus on which and how measurement
      properties should be assessed, and on criteria for good measurement properties.
      Two sources of input will be used for the Delphi study: (1) a systematic review
      of properties, standards and criteria of measurement properties found in
      systematic reviews of measurement instruments, and (2) an additional literature
      search of methodological articles presenting a comprehensive checklist of
      standards and criteria. The Delphi study will consist of four (written) Delphi
      rounds, with approximately 30 expert panel members with different backgrounds in
      clinical medicine, biostatistics, psychology, and epidemiology. The final
      checklist will subsequently be field-tested by assessing the inter-rater
      reproducibility of the checklist. DISCUSSION: Since the study will mainly be
      anonymous, problems that are commonly encountered in face-to-face group meetings,
      such as the dominance of certain persons in the communication process, will be
      avoided. By performing a Delphi study and involving many experts, the likelihood
      that the checklist will have sufficient credibility to be accepted and
      implemented will increase.

PMID- 16433904
TI  - Molecular phylogenetics and comparative modeling of HEN1, a methyltransferase
      involved in plant microRNA biogenesis.
AB  - BACKGROUND: Recently, HEN1 protein from Arabidopsis thaliana was discovered as an
      essential enzyme in plant microRNA (miRNA) biogenesis. HEN1 transfers a methyl
      group from S-adenosylmethionine to the 2'-OH or 3'-OH group of the last
      nucleotide of miRNA/miRNA* duplexes produced by the nuclease Dicer. Previously it
      was found that HEN1 possesses a Rossmann-fold methyltransferase (RFM) domain and
      a long N-terminal extension including a putative double-stranded RNA-binding
      motif (DSRM). However, little is known about the details of the structure and the
      mechanism of action of this enzyme, and about its phylogenetic origin. RESULTS:
      Extensive database searches were carried out to identify orthologs and close
      paralogs of HEN1. Based on the multiple sequence alignment a phylogenetic tree of
      the HEN1 family was constructed. The fold-recognition approach was used to
      identify related methyltransferases with experimentally solved structures and to
      guide the homology modeling of the HEN1 catalytic domain. Additionally, we
      identified a La-like predicted RNA binding domain located C-terminally to the
      DSRM domain and a domain with a peptide prolyl cis/trans isomerase (PPIase) fold,
      but without the conserved PPIase active site, located N-terminally to the
      catalytic domain. CONCLUSION: The bioinformatics analysis revealed that the
      catalytic domain of HEN1 is not closely related to any known RNA:2'-OH
      methyltransferases (e.g. to the RrmJ/fibrillarin superfamily), but rather to
      small-molecule methyltransferases. The structural model was used as a platform to
      identify the putative active site and substrate-binding residues of HEN and to
      propose its mechanism of action.

PMID- 16433906
TI  - Increased therapeutic potential of an experimental anti-mitotic inhibitor
      SB715992 by genistein in PC-3 human prostate cancer cell line.
AB  - BACKGROUND: Kinesin spindle proteins (KSP) are motor proteins that play an
      essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the
      formation of the bipolar spindle, which is critical for proper cell division
      during mitosis. The function of HsEg5 provides a novel target for the
      manipulation of the cell cycle and the induction of apoptosis. SB715992, an
      experimental KSP inhibitor, has been shown to perturb bipolar spindle formation,
      thus making it an excellent candidate for anti-cancer agent. Our major objective
      was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3
      human prostate cancer cell line, b) to investigate whether the growth inhibitory
      effects of SB715992 could be enhanced when combined with genistein, a naturally
      occurring isoflavone and, c) to determine gene expression profile to establish
      molecular mechanism of action of SB715992. METHODS: PC-3 cells were treated with
      varying concentration of SB715992, 30 microM of genistein, and SB715992 plus 30
      microM of genistein. After treatments, PC-3 cells were assayed for cell
      proliferation, induction of apoptosis, and alteration in gene and protein
      expression using cell inhibition assay, apoptosis assay, microarray analysis,
      real-time RT-PCR, and Western Blot analysis. RESULTS: SB715992 inhibited cell
      proliferation and induced apoptosis in PC-3 cells. SB715992 was found to regulate
      the expression of genes related to the control of cell proliferation, cell cycle,
      cell signaling pathways, and apoptosis. In addition, our results showed that
      combination treatment with SB715992 and genistein caused significantly greater
      cell growth inhibition and induction of apoptosis compared to the effects of
      either agent alone. CONCLUSION: Our results clearly show that SB715992 is a
      potent anti-tumor agent whose therapeutic effects could be enhanced by genistein.
      Hence, we believe that SB715992 could be a novel agent for the treatment of
      prostate cancer with greater success when combined with a non-toxic natural agent
      like genistein.

PMID- 16433907
TI  - High resolution physical map of porcine chromosome 7 QTL region and comparative
      mapping of this region among vertebrate genomes.
AB  - BACKGROUND: On porcine chromosome 7, the region surrounding the Major
      Histocompatibility Complex (MHC) contains several Quantitative Trait Loci (QTL)
      influencing many traits including growth, back fat thickness and carcass
      composition. Previous studies highlighted that a fragment of approximately 3.7 Mb
      is located within the Swine Leucocyte Antigen (SLA) complex. Internal
      rearrangements of this fragment were suggested, and partial contigs had been
      built, but further characterization of this region and identification of all
      human chromosomal fragments orthologous to this porcine fragment had to be
      carried out. RESULTS: A whole physical map of the region was constructed by
      integrating Radiation Hybrid (RH) mapping, BAC fingerprinting data of the INRA
      BAC library and anchoring BAC end sequences on the human genome. 17 genes and 2
      reference microsatellites were ordered on the high resolution IMNpRH212000rad
      Radiation Hybrid panel. A 1000:1 framework map covering 550 cR12000 was
      established and a complete contig of the region was developed. New micro
      rearrangements were highlighted between the porcine and human genomes. A bovine
      RH map was also developed in this region by mapping 16 genes. Comparison of the
      organization of this region in pig, cattle, human, mouse, dog and chicken genomes
      revealed that 1) the translocation of the fragment described previously is
      observed only on the bovine and porcine genomes and 2) the new internal micro
      rearrangements are specific of the porcine genome. CONCLUSION: We estimate that
      the region contains several rearrangements and covers 5.2 Mb of the porcine
      genome. The study of this complete BAC contig showed that human chromosomal
      fragments homologs of this heavily rearranged QTL region are all located in the
      region of HSA6 that surrounds the centromere. This work allows us to define a
      list of all candidate genes that could explain these QTL effects.

PMID- 16433908
TI  - Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae
      induced up-regulation of human beta-defensin 2 in middle ear epithelial cells.
AB  - BACKGROUND: We recently showed that beta-defensins have antimicrobial activity
      against nontypeable Haemophilus influenzae (NTHi) and that interleukin 1 alpha
      (IL-1 alpha) up-regulates the transcription of beta-defensin 2 (DEFB4 according
      to new nomenclature of the Human Genome Organization) in human middle ear
      epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on
      these observations, we investigated if human middle ear epithelial cells could
      release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could
      have a synergistic effect on beta-defensin 2 up-regulation by the bacterial
      components. METHODS: The studies described herein were carried out using
      epithelial cell lines as well as a murine model of acute otitis media (OM). Human
      cytokine macroarray analysis was performed to detect the released cytokines in
      response to NTHi exposure. Real time quantitative PCR was done to compare the
      induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling
      pathways involved. Direct activation of the beta-defensin 2 promoter was
      monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha
      blocking antibody was used to demonstrate the direct involvement of this cytokine
      on DEFB4 induction. RESULTS: Middle ear epithelial cells released IL-1 alpha when
      stimulated by NTHi components and this cytokine acted in an autocrine/paracrine
      synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic
      effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be
      mediated by the p38 MAP kinase pathway. CONCLUSION: We demonstrate that IL-1
      alpha is secreted by middle ear epithelial cells upon exposure to NTHi components
      and that it can synergistically act with certain of these molecules to up
      regulate beta-defensin 2 via the p38 MAP kinase pathway.

PMID- 16433910
TI  - Measurement of complement receptor 1 on neutrophils in bacterial and viral
      pneumonia.
AB  - BACKGROUND: A reliable prediction of the causative agent of community-acquired
      pneumonia (CAP) is not possible based on clinical features. Our aim was to test,
      whether the measurement of the expression of complement receptors or Fcgamma
      receptors on neutrophils and monocytes would be a useful preliminary test to
      differentiate between bacterial and viral pneumonia. METHODS: Sixty-eight
      patients with CAP were studied prospectively. Thirteen patients had pneumococcal
      pneumonia; 13 patients, influenza A pneumonia; 5 patients, atypical pneumonia,
      and 37 patients, aetiologically undefined pneumonia. Leukocyte receptor
      expression was measured within 2 days of hospital admission. RESULTS: The mean
      expression of complement receptor 1 (CR1) on neutrophils was significantly higher
      in the patients with pneumococcal pneumonia than in those with influenza A
      pneumonia. The mean expression of CR1 was also significantly higher in
      aetiologically undefined pneumonia than in influenza A pneumonia, but there was
      no difference between pneumococcal and undefined pneumonia. CONCLUSION: Our
      results suggest that the expression of CR1 is higher in classical bacterial
      pneumonia than in viral pneumonia. Determination of the expression of CR1 may be
      of value as an additional rapid tool in the aetiological diagnosis, bacterial or
      viral infection, of CAP. These results are preliminary and more research is
      needed to assess the utility of this new method in the diagnostics of pneumonia.

PMID- 16433909
TI  - On the effects of cycloheximide on cell motility and polarisation in
      Dictyostelium discoideum.
AB  - BACKGROUND: Cycloheximide is a protein synthesis inhibitor that acts specifically
      on the 60S subunit of eukaryotic ribosomes. It has previously been shown that a
      short incubation of Dictyostelium discoideum amoebae in cycloheximide eliminates
      fluid phase endocytosis. RESULTS: We found that treatment with cycloheximide also
      causes the amoebae to retract their pseudopodia, round up and cease movement.
      Furthermore, fluid phase endocytosis, phagocytosis and capping cease in the
      presence of 2 mM cycloheximide, although membrane uptake, as measured using FM1
      43, is unaffected. In the presence of cycloheximide, aggregation-competent
      amoebae sensitive to cAMP, although round, can still localise CRAC, ABP120, PI3K
      and actin polymerisation in response to a micropipette filled with cAMP. The
      behaviour of wild-type amoebae in the presence of cycloheximide is surprisingly
      similar to that of amoebae having a temperature-sensitive version of NSF at the
      restrictive temperature. CONCLUSION: Our results may suggest that, upon
      cycloheximide treatment, either a labile protein required for polarised membrane
      recycling is lost, or a control mechanism linking protein synthesis to membrane
      recycling is activated.

PMID- 16433911
TI  - Why is public science education important?

PMID- 16433913
TI  - Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly
      Active Antiretroviral Therapy.
AB  - BACKGROUND: The effects of HAART may differ between children and adults because
      children have a developing immune system, and the long-term immunological outcome
      in HIV-infected children on HAART is not well-known. A major aim of our study was
      to determine CD4+ evolution associated with long-term VL control during 4 years
      of observation on HAART. METHODS: We carried out a retrospective study on a
      cohort of 160 vertically HIV-infected children. It was carried out from 1996 to
      2004 in six large Spanish pediatric referral hospitals. We compared 33 children
      who had long-term VL suppression (VL < or = 400 copies/ml) in the first 12 months
      of follow-up and maintained that level throughout follow-up (Responders-group),
      and 127 children with persistently detectable VL in spite of ART switches (Non
      Responders-group). RESULTS: We observed a quick initial and significant increase
      in CD4+ counts from the baseline to 12 months on HAART in both groups (p < 0.01).
      The Non-Responders group sustained CD4+ increases and most of these children
      maintained high CD4+ level counts (> or = 25%). The Non-Responders group reached
      a plateau between 26% and 27% CD4+ at the first 12 months of follow-up that
      remained stable during the following 3 years. However, the Responders group
      reached a plateau between 30% and 32% CD4+ at 24, 36 and 48 months of follow-up.
      We found that the Responders group had higher CD4+ count values and higher
      percentages of children with CD4+ > or = 25% than the Non-Responders group (p <
      0.05) after month 12. CONCLUSION: Long-term VL suppression in turn induces large
      beneficial effects in immunological responses. However, it is not indispensable
      to recover CD4+ levels.

PMID- 16433912
TI  - Effects of lipopolysaccharide-induced inflammation on expression of growth
      associated genes by corticospinal neurons.
AB  - BACKGROUND: Inflammation around cell bodies of primary sensory neurons and
      retinal ganglion cells enhances expression of neuronal growth-associated genes
      and stimulates axonal regeneration. We have asked if inflammation would have
      similar effects on corticospinal neurons, which normally show little response to
      spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of
      the motor cortex of adult rats with or without concomitant injury of the
      corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in
      the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and
      macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and
      GAP-43 was investigated by immunohistochemistry or in situ hybridisation.
      RESULTS: Application of LPS induced a gradient of inflammation through the full
      depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2
      weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had
      very limited effects on neuronal ATF3 expression. However, many glial cells in
      the subcortical white matter upregulated ATF3. LPS did not promote sprouting of
      anterogradely labelled corticospinal axons, which did not grow into or beyond a
      cervical lesion site. CONCLUSION: Inflammation produced by topical application of
      LPS promoted increased expression of some growth-associated genes in the cell
      bodies of corticospinal neurons, but was insufficient to promote regeneration of
      the corticospinal tract.

PMID- 16433914
TI  - Patterns of drug use among a sample of drug users and injecting drug users
      attending a General Practice in Iran.
AB  - AIM: This study aimed to examine drug use, drug treatment history and risk
      behaviour among a sample of Iranian drug users seeking treatment through a
      general practice clinic in Iran. METHODS: Review of medical records and an intake
      questionnaire at a large general practice in Marvdasht, Iran, with a special
      interest in drug dependence treatment. Records from a random sample of injecting
      drug users (IDU), non-injecting drug users (DU) and non-drug using patients were
      examined. RESULTS: 292 records were reviewed (34% IDU, 31% DU and 35% non-drug
      users). Eighty-three percent were males; all females were non-drug users. The
      mean age of the sample was 30 years. Of the IDU sample, 67% reported sharing a
      needle or syringe, 19% of these had done so in prison. Of those who had ever used
      drugs, being 'tired' of drug use was the most common reason for seeking help
      (34%). Mean age of first drug use was 20 years. The first drugs most commonly
      used were opium (72%), heroin (13%) and hashish/ other cannabinoids (13%). Three
      quarters reported having previously attempted to cease their drug use. IDU were
      more likely than DU to report having ever been imprisoned (41% vs 7%) and 41% to
      have used drugs in prison. CONCLUSION: This study has shown that there is a need
      for general practice clinics in Iran to treat drug users including those who
      inject and that a substantial proportion of those who inject have shared needles
      and syringes, placing them at risk of BBVI such as HIV and hepatitis C. The
      expansion of services for drug users in Iran such as needle and syringe programs
      and pharmacotherapies are likely to be effective in reducing the harms associated
      with opium use and heroin injection.

PMID- 16433916
TI  - Effect of lateral perturbations on psychophysical acceleration detection
      thresholds.
AB  - BACKGROUND: In understanding how the human body perceives and responds to small
      slip-like motions, information on how one senses the slip is essential. The
      effect of aging and plantar sensory loss on detection of a slip can also be
      studied. Using psychophysical procedures, acceleration detection thresholds of
      small lateral whole-body perturbations were measured for healthy young adults
      (HYA), healthy older adults (HOA) and older adults with diabetic neuropathy
      (DOA). It was hypothesized that young adults would require smaller accelerations
      than HOA's and DOA's to detect perturbations at a given displacement. METHODS:
      Acceleration detection thresholds to whole-body lateral perturbations of 1, 2, 4,
      8, and 16 mm were measured for HYAs, HOAs, and DOAs using psychophysical
      procedures including a two-alternative forced choice protocol. Based on the
      subject's detection of the previous trial, the acceleration magnitude of the
      subsequent trial was increased or decreased according to the parameter estimation
      by sequential testing methodology. This stair-stepping procedure allowed
      acceleration thresholds to be measured for each displacement. RESULTS: Results
      indicate that for lateral displacements of 1 and 2 mm, HOAs and DOAs have
      significantly higher acceleration detection thresholds than young adults. At
      displacements of 8 and 16 mm, no differences in threshold were found among groups
      or between the two perturbation distances. The relationship between the
      acceleration threshold and perturbation displacement is of particular interest.
      Peak acceleration thresholds of approximately 10 mm/s(2) were found at
      displacements of 2, 4, 8, and 16 mm for HYAs; at displacements of 4, 8, and 16 mm
      for HOAs; and at displacements of 8 and 16 mm for DOAs. Thus, 2, 4, and 8 mm
      appear to be critical breakpoints for HYAs, HOAs, and DOAs respectively, where
      the psychometric curve deviated from a negative power law relationship. These
      critical breakpoints likely indicate a change in the physiology of the system as
      it responds to the stimuli. CONCLUSION: As a function of age, the displacement at
      which the group deviates from a negative power law relationship increases from 2
      mm to 4 mm. Additionally, the displacement at which subjects with peripheral
      sensory deficits deviate from the negative power law relations increases to 8 mm.
      These increases as a function of age and peripheral sensory loss may help explain
      the mechanism of falls in the elderly and diabetic populations.

PMID- 16433915
TI  - CoSMoS: Conserved Sequence Motif Search in the proteome.
AB  - BACKGROUND: With the ever-increasing number of gene sequences in the public
      databases, generating and analyzing multiple sequence alignments becomes
      increasingly time consuming. Nevertheless it is a task performed on a regular
      basis by researchers in many labs. RESULTS: We have now created a database called
      CoSMoS to find the occurrences and at the same time evaluate the significance of
      sequence motifs and amino acids encoded in the whole genome of the model organism
      Escherichia coli K12. We provide a precomputed set of multiple sequence
      alignments for each individual E. coli protein with all of its homologues in the
      RefSeq database. The alignments themselves, information about the occurrence of
      sequence motifs together with information on the conservation of each of the more
      than 1.3 million amino acids encoded in the E. coli genome can be accessed via
      the web interface of CoSMoS. CONCLUSION: CoSMoS is a valuable tool to identify
      highly conserved sequence motifs, to find regions suitable for mutational studies
      in functional analyses and to predict important structural features in E. coli
      proteins.

PMID- 16433917
TI  - Gender differences in health-related quality of life of adolescents with cystic
      fibrosis.
AB  - BACKGROUND: Female patients with cystic fibrosis (CF) have consistently poorer
      survival rates than males across all ages. To determine if gender differences
      exist in health-related quality of life (HRQOL) of adolescent patients with CF,
      we performed a cross-section analysis of CF patients recruited from 2 medical
      centers in 2 cities during 1997-2001. METHODS: We used the 87-item child self
      report form of the Child Health Questionnaire to measure 12 health domains. Data
      was also collected on age and forced expiratory volume in 1 second (FEV1). We
      analyzed data from 98 subjects and performed univariate analyses and linear
      regression or ordinal logistic regression for multivariable analyses. RESULTS:
      The mean (SD) age was 14.6 (2.5) years; 50 (51.0%) were female; and mean FEV1 was
      71.6% (25.6%) of predicted. There were no statistically significant gender
      differences in age or FEV1. In univariate analyses, females reported
      significantly poorer HRQOL in 5 of the 12 domains. In multivariable analyses
      controlling for FEV1 and age, we found that female gender was associated with
      significantly lower global health (p < 0.05), mental health (p < 0.01), and
      general health perceptions (p < 0.05) scores. CONCLUSION: Further research will
      need to focus on the causes of these differences in HRQOL and on potential
      interventions to improve HRQOL of adolescent patients with CF.

PMID- 16433918
TI  - Recruitment of aged donor heart with pharmacological stress echo. A case report.
AB  - BACKGROUND: The heart transplant is a treatment of the heart failure, which is
      not responding to medications, and its efficiency is already proved:
      unfortunately, organ donation is a limiting step of this life-saving procedure.
      To counteract heart donor shortage, we should screen aged potential donor hearts
      for initial cardiomyopathy and functionally significant coronary artery disease.
      Donors with a history of cardiac disease are generally excluded. Coronary
      angiography is recommended for most male donors older than 45 years and female
      donors older than 50 years to evaluate coronary artery stenoses. A simpler way to
      screen aged potential donor hearts for initial cardiomyopathy and functionally
      significant coronary artery disease should be stress echocardiography. CASE
      REPORT: A marginal donor (A 57 year old woman meeting legal requirements for
      brain death) underwent a transesophageal (TE) Dipyridamole stress echo (6 minutes
      accelerated protocol) to rule out moderate or severe heart and coronary artery
      disease. Wall motion was normal at baseline and at peak stress (WMSI = 1 at
      baseline and peak stress, without signs of stress inducible ischemia). The
      pressure/volume ratio was 9.6 mmHg/ml/m2 at baseline, increasing to 14 mmHg/ml/m2
      at peak stress, demonstrating absence of latent myocardial dysfunction. The
      marginal donor heart was transplanted to a recipient "marginal" for co-morbidity
      (a 63 year old man with multiple myeloma and cardiac amyloidosis, chronic severe
      heart failure, NYHA class IV). Postoperative treatment and early
      immunosuppressant regimen were performed according to standard protocols. The
      transplanted heart was assessed normal for dimensions and ventricular function at
      transthoracic (TT) echocardiography on post-transplant day 7. Coronary artery
      disease was ruled out at coronary angiography one month after transplant; left
      ventriculography showed normal global and segmental LV function of the
      transplanted heart. CONCLUSION: For the first time stress echo was successfully
      used in the critical theater of screening potential donor hearts. This method is
      enormously more feasible, less expensive, and more environmentally sustainable
      than any possible alternative strategy based on stress scintigraphy perfusion
      imaging or coronary angiography. The selection of hearts "too good to die" on the
      basis of bedside resting and stress echo can be a critical way to solve the
      mismatch between donor need and supply.

PMID- 16433919
TI  - A novel approach for rapid screening of mitochondrial D310 polymorphism.
AB  - BACKGROUND: Mutations in the mitochondrial DNA (mtDNA) have been reported in a
      wide variety of human neoplasms. A polynucleotide tract extending from 303 to 315
      nucleotide positions (D310) within the non-coding region of mtDNA has been
      identified as a mutational hotspot of primary tumors. This region consists of two
      polycytosine stretches interrupted by a thymidine nucleotide. The number of
      cytosines at the first and second stretches are 7 and 5 respectively, according
      to the GeneBank sequence. The first stretch exhibits a polymorphic length
      variation (6-C to 9-C) among individuals and has been investigated in many cancer
      types. Large-scale studies are needed to clarify the relationship between
      cytosine number and cancer development/progression. However, time and money
      consuming methods such as radioactivity-based gel electrophoresis and sequencing,
      are not appropriate for the determination of this polymorphism for large case
      control studies. In this study, we conducted a rapid RFLP analysis using a
      restriction enzyme, BsaXI, for the single step simple determination of 7-C
      carriers at the first stretch in D310 region. METHODS: 25 colorectal cancer
      patients, 25 breast cancer patients and 41 healthy individuals were enrolled into
      the study. PCR amplification followed by restriction enzyme digestion of D310
      region was performed for RFLP analysis. Digestion products were analysed by
      agarose gel electrophoresis. Sequencing was also applied to samples in order to
      confirm the RFLP data. RESULTS: Samples containing 7-C at first stretch of D310
      region were successfully determined by the BsaXI RFLP method. Heteroplasmy and
      homoplasmy for 7-C content was also determined as evidenced by direct sequencing.
      Forty-one percent of the studied samples were found to be BsaXI positive.
      Furthermore, BsaXI status of colorectal cancer samples were significantly
      different from that of healthy individuals. CONCLUSION: In conclusion, BsaXI RFLP
      analysis is a simple and rapid approach for the single step determination of D310
      polymorphism of mitochondrial DNA. This method allows the evaluation of a
      significant proportion of samples without the need for sequencing- and/or
      radioactivity-based techniques.

PMID- 16433920
TI  - Budesonide/formoterol and formoterol provide similar rapid relief in patients
      with acute asthma showing refractoriness to salbutamol.
AB  - BACKGROUND: To compare the efficacy and safety of budesonide/formoterol
      (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma
      who showed evidence of refractoriness to short-acting beta2-agonist therapy.
      METHODS: In a 3 hour, randomized, double-blind study, a total of 115 patients
      with acute asthma (mean FEV1 40% of predicted normal) and a refractory response
      to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400
      microg), were randomized to receive either budesonide/formoterol (320/9 microg, 2
      inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36
      microg]) or formoterol (9 microg, 2 inhalations at t = -5 minutes and 2
      inhalations at 0 minutes [total dose 36 microg]). The primary efficacy variable
      was the average FEV1 from the first intake of study medication to the measurement
      at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints
      and change in respiratory rate at 180 minutes. Treatment success, treatment
      failure and patient assessment of the effectiveness of the study medication were
      also measured. RESULTS: FEV1 increased after administration of the study
      medication in both treatment groups. No statistically significant difference
      between the treatment groups was apparent for the primary outcome variable, or
      for any of the other efficacy endpoints. There were no statistically significant
      between-group differences for treatment success, treatment failure or patient
      assessment of medication effectiveness. Both treatments were well tolerated.
      CONCLUSION: Budesonide/formoterol and formoterol provided similarly rapid relief
      of acute bronchoconstriction in patients with asthma who showed evidence of
      refractoriness to a short-acting beta2-agonist.

PMID- 16433922
TI  - Analysis of molecular diversity, population structure and linkage disequilibrium
      in a worldwide survey of cultivated barley germplasm (Hordeum vulgare L.).
AB  - BACKGROUND: The goal of our study was a systematic survey of the molecular
      diversity in barley genetic resources. To this end 953 cultivated barley
      accessions originating from all inhabited continents except Australia were
      genotyped with 48 SSR markers. Molecular diversity was evaluated with routine
      statistics (allelic richness, gene diversity, allele frequency, heterozygosity
      and unique alleles), Principal Coordinate Analysis (PCoA), and analysis of genome
      wide linkage disequilibrium. RESULTS: A genotyping database for 953 cultivated
      barley accessions profiled with 48 SSR markers was established. The PCoA revealed
      structuring of the barley population with regard to (i) geographical regions and
      (ii) agronomic traits. Geographic origin contributed most to the observed
      molecular diversity. Genome-wide linkage disequilibrium (LD) was estimated as
      squared correlation of allele frequencies (r2). The values of LD for barley were
      comparable to other plant species (conifers, poplar, maize). The pattern of
      intrachromosomal LD with distances between the genomic loci ranging from 1 to 150
      cM revealed that in barley LD extended up to distances as long as 50 cM with r2 >
      0.05, or up to 10 cM with r2 > 0.2. Few loci mapping to different chromosomes
      showed significant LD with r2 > 0.05. The number of loci in significant LD as
      well as the pattern of LD were clearly dependent on the population structure. The
      LD in the homogenous group of 207 European 2-rowed spring barleys compared to the
      highly structured worldwide barley population was increased in the number of loci
      pairs with r2 > 0.05 and had higher values of r2, although the percentage of
      intrachromosomal loci pairs in significant LD based on P < 0.001 was 100% in the
      whole set of varieties, but only 45% in the subgroup of European 2-rowed spring
      barleys. The value of LD also varied depending on the polymorphism of the loci
      selected for genotyping. The 17 most polymorphic loci (PIC > 0.80) provided
      higher LD values as compared to 19 low polymorphic loci (PIC < 0.73) in both
      structured (all accessions) and non-structured (European 2-rowed spring
      varieties) barley populations. CONCLUSION: A global population of cultivated
      barley accessions was highly structured. Clustering highlighted the accessions
      with the same geographic origin, as well as accessions possessing similar
      agronomic characters. LD in barley extended up to 50 cM, and was strongly
      dependent on the population structure. The data on LD were summarized as a genome
      wide LD map for barley.

PMID- 16433921
TI  - Non-topographical contrast enhancement in the olfactory bulb.
AB  - BACKGROUND: Contrast enhancement within primary stimulus representations is a
      common feature of sensory systems that regulates the discrimination of similar
      stimuli. Whereas most sensory stimulus features can be mapped onto one or two
      dimensions of quality or location (e.g., frequency or retinotopy), the analogous
      similarities among odor stimuli are distributed high-dimensionally, necessarily
      yielding a chemotopically fragmented map upon the surface of the olfactory bulb.
      While olfactory contrast enhancement has been attributed to decremental lateral
      inhibitory processes among olfactory bulb projection neurons modeled after those
      in the retina, the two-dimensional topology of this mechanism is intrinsically
      incapable of mediating effective contrast enhancement on such fragmented maps.
      Consequently, current theories are unable to explain the existence of olfactory
      contrast enhancement. RESULTS: We describe a novel neural circuit mechanism, non
      topographical contrast enhancement (NTCE), which enables contrast enhancement
      among high-dimensional odor representations exhibiting unpredictable patterns of
      similarity. The NTCE algorithm relies solely on local intraglomerular
      computations and broad feedback inhibition, and is consistent with known
      properties of the olfactory bulb input layer. Unlike mechanisms based upon
      lateral projections, NTCE does not require a built-in foreknowledge of the
      similarities in molecular receptive ranges expressed by different olfactory bulb
      glomeruli, and is independent of the physical location of glomeruli within the
      olfactory bulb. CONCLUSION: Non-topographical contrast enhancement demonstrates
      how intrinsically high-dimensional sensory data can be represented and processed
      within a physically two-dimensional neural cortex while retaining the capacity to
      represent stimulus similarity. In a biophysically constrained computational model
      of the olfactory bulb, NTCE successfully mediates contrast enhancement among
      odorant representations in the natural, high-dimensional similarity space defined
      by the olfactory receptor complement and underlies the concentration-independence
      of odor quality representations.

PMID- 16433924
TI  - Loss of NAD(H) from swollen yeast mitochondria.
AB  - BACKGROUND: The mitochondrial electron transport chain oxidizes matrix space NADH
      as part of the process of oxidative phosphorylation. Mitochondria contain
      shuttles for the transport of cytoplasmic NADH reducing equivalents into the
      mitochondrial matrix. Therefore for a long time it was believed that NAD(H)
      itself was not transported into mitochondria. However evidence has been obtained
      for the transport of NAD(H) into and out of plant and mammalian mitochondria.
      Since Saccharomyces cerevisiae mitochondria can directly oxidize cytoplasmic
      NADH, it remained questionable if mitochondrial NAD(H) transport occurs in this
      organism. RESULTS: NAD(H) was lost more extensively from the matrix space of
      swollen than normal, condensed isolated yeast mitochondria from Saccharomyces
      cerevisiae. The loss of NAD(H) in swollen organelles caused a greatly decreased
      respiratory rate when ethanol or other matrix space NAD-linked substrates were
      oxidized. Adding NAD back to the medium, even in the presence of a membrane
      impermeant NADH dehydrogenase inhibitor, restored the respiratory rate of swollen
      mitochondria oxidizing ethanol, suggesting that NAD is transported into the
      matrix space. NAD addition did not restore the decreased respiratory rate of
      swollen mitochondria oxidizing the combination of malate, glutamate, and
      pyruvate. Therefore the loss of matrix space metabolites is not entirely specific
      for NAD(H). However, during NAD(H) loss the mitochondrial levels of most other
      nucleotides were maintained. Either hypotonic swelling or colloid-osmotic
      swelling due to opening of the yeast mitochondrial unspecific channel (YMUC) in a
      mannitol medium resulted in decreased NAD-linked respiration. However, the loss
      of NAD(H) from the matrix space was not mediated by the YMUC, because YMUC
      inhibitors did not prevent decreased NAD-linked respiration during swelling and
      YMUC opening without swelling did not cause decreased NAD-linked respiration.
      CONCLUSION: Loss of endogenous NAD(H) from isolated yeast mitochondria is greatly
      stimulated by matrix space expansion. NAD(H) loss greatly limits NAD-linked
      respiration in swollen mitochondria without decreasing the NAD-linked respiratory
      rate in normal, condensed organelles. NAD addition can totally restore the
      decreased respiration in swollen mitochondria. In live yeast cells mitochondrial
      swelling has been observed prior to mitochondrial degradation and cell death.
      Therefore mitochondrial swelling may stimulate NAD(H) transport to regulate
      metabolism during these conditions.

PMID- 16433923
TI  - Colour variation in red grapevines (Vitis vinifera L.): genomic organisation,
      expression of flavonoid 3'-hydroxylase, flavonoid 3',5'-hydroxylase genes and
      related metabolite profiling of red cyanidin-/blue delphinidin-based anthocyanins
      in berry skin.
AB  - BACKGROUND: Structural genes of the phenyl-propanoid pathway which encode
      flavonoid 3'- and 3',5'-hydroxylases (F3'H and F3'5'H) have long been invoked to
      explain the biosynthesis of cyanidin- and delphinidin-based anthocyanin pigments
      in the so-called red cultivars of grapevine. The relative proportion of the two
      types of anthocyanins is largely under genetic control and determines the colour
      variation among red/purple/blue berry grape varieties and their corresponding
      wines. RESULTS: Gene fragments of VvF3'H and VvF3'5'H, that were isolated from
      Vitis vinifera 'Cabernet Sauvignon' using degenerate primers designed on plant
      homologous genes, translated into 313 and 239 amino acid protein fragments,
      respectively, with up to 76% and 82% identity to plant CYP75 cytochrome P450
      monooxygenases. Putative function was assigned on the basis of sequence homology,
      expression profiling and its correlation with metabolite accumulation at ten
      different ripening stages. At the onset of colour transition, transcriptional
      induction of VvF3'H and VvF3'5'H was temporally coordinated with the beginning of
      anthocyanin biosynthesis, the expression being 2-fold and 50-fold higher,
      respectively, in red berries versus green berries. The peak of VvF3'5'H
      expression was observed two weeks later concomitantly with the increase of the
      ratio of delphinidin-/cyanidin-derivatives. The analysis of structural genomics
      revealed that two copies of VvF3'H are physically linked on linkage group no. 17
      and several copies of VvF3'5'H are tightly clustered and embedded into a
      segmental duplication on linkage group no. 6, unveiling a high complexity when
      compared to other plant flavonoid hydroxylase genes known so far, mostly in
      ornamentals. CONCLUSION: We have shown that genes encoding flavonoid 3'- and
      3',5'-hydroxylases are expressed in any tissues of the grape plant that
      accumulate flavonoids and, particularly, in skin of ripening red berries that
      synthesise mostly anthocyanins. The correlation between transcript profiles and
      the kinetics of accumulation of red/cyanidin- and blue/delphinidin-based
      anthocyanins indicated that VvF3'H and VvF3'5'H expression is consistent with the
      chromatic evolution of ripening bunches. Local physical maps constructed around
      the VvF3'H and VvF3'5'H loci should help facilitate the identification of the
      regulatory elements of each isoform and the future manipulation of grapevine and
      wine colour through agronomical, environmental and biotechnological tools.

PMID- 16433925
TI  - Criteria for effective design, construction, and gene knockdown by shRNA vectors.
AB  - BACKGROUND: RNA interference (RNAi) technology is a powerful methodology recently
      developed for the specific knockdown of targeted genes. RNAi is most commonly
      achieved either transiently by transfection of small interfering (si) RNA
      oligonucleotides, or stably using short hairpin (sh) RNA expressed from a DNA
      vector or virus. Much controversy has surrounded the development of rules for the
      design of effective siRNA oligonucleotides; and whether these rules apply to
      shRNA is not well characterized. RESULTS: To determine whether published
      algorithms for siRNA oligonucleotide design apply to shRNA, we constructed 27
      shRNAs from 11 human genes expressed stably using retroviral vectors. We
      demonstrate an efficient method for preparing wild-type and mutant control shRNA
      vectors simultaneously using oligonucleotide hybrids. We show that sequencing
      through shRNA vectors can be problematic due to the intrinsic secondary structure
      of the hairpin, and we determine a strategy for effective sequencing by using a
      combination of modified BigDye chemistries and DNA relaxing agents. The efficacy
      of knockdown for the 27 shRNA vectors was evaluated against six published
      algorithms for siRNA oligonucleotide design. Our results show that none of the
      scoring algorithms can explain a significant percentage of variance in shRNA
      knockdown efficacy as assessed by linear regression analysis or ROC curve
      analysis. Application of a modification based on the stability of the 6 central
      bases of each shRNA provides fair-to-good predictions of knockdown efficacy for
      three of the algorithms. Analysis of an independent set of data from 38 shRNAs
      pooled from previous publications confirms these findings. CONCLUSION: The use of
      mixed oligonucleotide pairs provides a time and cost efficient method of
      producing wild type and mutant control shRNA vectors. The addition to sequencing
      reactions of a combination of mixed dITP/dGTP chemistries and DNA relaxing agents
      enables read through the intrinsic secondary structure of problematic shRNA
      vectors. Six published algorithms for siRNA oligonucleotide design that were
      tested in this study show little or no efficacy at predicting shRNA knockdown
      outcome. However, application of a modification based on the central shRNA
      stability should provide a useful improvement to the design of effective shRNA
      vectors.

PMID- 16433926
TI  - Lack of insurance coverage and urgent care use for asthma: a retrospective cohort
      study.
AB  - BACKGROUND: Asthma is a common chronic disease with profound impacts upon
      individuals and the US health care system. Inadequate health care coverage has
      been associated with more frequent and severe exacerbations of the disease. We
      examined the relationship between adequacy of health care coverage and use of
      emergent care of adults with asthma. METHODS: The 2001 Behavioral Risk Factor
      Surveillance System was the source of data on adults with current asthma.
      Bivariate and multiple logistic regression analysis modeled identifiable factors
      in predicting urgent or emergent care. RESULTS: Key variables included
      demographics and information on self-reported gaps in health care coverage. The
      primary outcome was emergency room or urgent care visits for worsening of asthma
      symptoms. Of 16,234 subjects nationally with current asthma, 2,195 from eight
      states had valid responses to a supplemental module asking about emergency room
      use or urgent care visits because of asthma. Thirty four percent of these
      individuals required such care in the previous year. Having an interruption in
      health care coverage in the past year was associated with an increased risk of
      needed urgent or emergent care (crude Odds Ratio [OR] 1.48, 95% confidence
      intervals [CI]1.03, 2.1). The association was not statistically significant in
      the adjusted multivariate model including race/ethnicity, employment status,
      gender, age, education and the ability to identify a primary physician (adjusted
      OR 1.2, 95% CI 0.8, 1.8). CONCLUSION: This study provides population-level,
      generalizable evidence of increased risk of exacerbations of asthma in adults and
      (1) their demographic characteristics, and (2) continuous adequate health care
      coverage.

PMID- 16433927
TI  - A community programme to reduce salt intake and blood pressure in Ghana
      [ISRCTN88789643].
AB  - BACKGROUND: In Africa hypertension is common and stroke is increasing. Detection,
      treatment and control of high blood pressure (BP) is limited. BP can be lowered
      by reducing salt intake. In Africa salt is added to the food by the consumer, as
      processed food is rare. A population-wide approach with programmes based on
      health education and promotion is thus possible. METHODS: We carried out a
      community-based cluster randomised trial of health promotion in 1,013
      participants from 12 villages (628 women, 481 rural dwellers); mean age 55 years
      to reduce salt intake and BP. Average BP was 125/74 mmHg and urinary sodium (UNa)
      101 mmol/day. A health promotion intervention was provided over 6 months to all
      villages. Assessments were made at 3 and 6 months. Primary end-points were
      urinary sodium excretion and BP levels. RESULTS: There was a significant positive
      relationship between salt intake and both systolic (2.17 mmHg [95% CI 0.44 to
      3.91] per 50 mmol of UNa per day, p < 0.001) and diastolic BP (1.10 mmHg [0.08 to
      1.94], p < 0.001) at baseline. At six months the intervention group showed a
      reduction in systolic (2.54 mmHg [-1.45 to 6.54]) and diastolic (3.95 mmHg [0.78
      to 7.11], p = 0.015) BP when compared to control. There was no significant change
      in UNa. Smaller villages showed greater reductions in UNa than larger villages (p
      = 0.042). Irrespective of randomisation, there was a consistent and significant
      relationship between change in UNa and change in systolic BP, when adjusted for
      confounders. A difference in 24-hour UNa of 50 mmol was associated with a lower
      systolic BP of 2.12 mmHg (1.03 to 3.21) at 3 months and 1.34 mmHg (0.08 to 2.60)
      at 6 months (both p < 0.001). CONCLUSION: In West Africa the lower the salt
      intake, the lower the BP. It would appear that a reduction in the average salt
      intake in the whole community may lead to a small but significant reduction in
      population systolic BP.

PMID- 16433928
TI  - MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in
      Metazoa.
AB  - BACKGROUND: Mitochondria are sub-cellular organelles that have a central role in
      energy production and in other metabolic pathways of all eukaryotic respiring
      cells. In the last few years, with more and more genomes being sequenced, a huge
      amount of data has been generated providing an unprecedented opportunity to use
      the comparative analysis approach in studies of evolution and functional genomics
      with the aim of shedding light on molecular mechanisms regulating mitochondrial
      biogenesis and metabolism. In this context, the problem of the optimal extraction
      of representative datasets of genomic and proteomic data assumes a crucial
      importance. Specialised resources for nuclear-encoded mitochondria-related
      proteins already exist; however, no mitochondrial database is currently available
      with the same features of MitoRes, which is an update of the MitoNuc database
      extensively modified in its structure, data sources and graphical interface. It
      contains data on nuclear-encoded mitochondria-related products for any metazoan
      species for which this type of data is available and also provides comprehensive
      sequence datasets (gene, transcript and protein) as well as useful tools for
      their extraction and export. DESCRIPTION: MitoRes
      http://www2.ba.itb.cnr.it/MitoRes/ consolidates information from publicly
      external sources and automatically annotates them into a relational database.
      Additionally, it also clusters proteins on the basis of their sequence similarity
      and interconnects them with genomic data. The search engine and sequence
      management tools allow the query/retrieval of the database content and the
      extraction and export of sequences (gene, transcript, protein) and related sub
      sequences (intron, exon, UTR, CDS, signal peptide and gene flanking regions)
      ready to be used for in silico analysis. CONCLUSION: The tool we describe here
      has been developed to support lab scientists and bioinformaticians alike in the
      characterization of molecular features and evolution of mitochondrial targeting
      sequences. The way it provides for the retrieval and extraction of sequences
      allows the user to overcome the obstacles encountered in the integrative use of
      different bioinformatic resources and the completeness of the sequence collection
      allows intra- and interspecies comparison at different biological levels (gene,
      transcript and protein).

PMID- 16433930
TI  - Morphological development of Aspergillus niger in submerged citric acid
      fermentation as a function of the spore inoculum level. Application of neural
      network and cluster analysis for characterization of mycelial morphology.
AB  - BACKGROUND: Although the citric acid fermentation by Aspergillus niger is one of
      the most important industrial microbial processes and various aspects of the
      fermentation appear in a very large number of publications since the 1950s, the
      effect of the spore inoculum level on fungal morphology is a rather neglected
      area. The aim of the presented investigations was to quantify the effects of
      changing spore inoculum level on the resulting mycelial morphology and to
      investigate the physiology that underlines the phenomena. Batch fermentations
      were carried out in a stirred tank bioreactor, which were inoculated directly
      with spores in concentrations ranging from 10(4) to 10(9) spores per ml.
      Morphological features, evaluated by digital image analysis, were classified
      using an artificial neural network (ANN), which considered four main object
      types: globular and elongated pellets, clumps and free mycelial trees. The
      significance of the particular morphological features and their combination was
      determined by cluster analysis. RESULTS: Cell volume fraction analysis for the
      various inoculum levels tested revealed that by rising the spore inoculum level
      from 10(4) to 10(9) spores per ml, a clear transition from pelleted to dispersed
      forms occurs. Glucosamine formation and release by the mycelium appears to be
      related to spore inoculum level. Maximum concentrations detected in fermentations
      inoculated with 10(4) and 10(5) spores/ml, where pellets predominated. At much
      higher inoculum levels (10(8), 10(9) spores/ml), lower dissolved oxygen levels
      during the early fermentation phase were associated with slower ammonium ions
      uptakes and significantly lower glucosamine concentrations while the mycelium
      developed in dispersed morphologies. A big increase in the main and total hyphal
      lengths and branching frequency was observed in mycelial trees as inoculum levels
      rise from 10(4) to 10(9) spores/ml, while in aggregated forms particle sizes and
      their compactness decreased. CONCLUSION: The methods used in this study, allowed
      for the detailed quantification of the transition between the two extreme
      morphological forms. The impact of spore inoculum level on the detailed
      characteristics of the particular morphological forms produced was high. Control
      of mycelial morphology is often regarded as a prerequisite to ensure increased
      productivities in industrial applications. The research described here
      demonstrates that adjusting the spore inoculum level controls effectively
      mycelial morphology.

PMID- 16433929
TI  - m-Calpain is required for preimplantation embryonic development in mice.
AB  - BACKGROUND: Mu-calpain and m-calpain are ubiquitously expressed proteases
      implicated in cellular migration, cell cycle progression, degenerative processes
      and cell death. These heterodimeric enzymes are composed of distinct catalytic
      subunits, encoded by Capn1 (mu-calpain) or Capn2 (m-calpain), and a common
      regulatory subunit encoded by Capn4. Disruption of the mouse Capn4 gene abolished
      both mu-calpain and m-calpain activity, and resulted in embryonic lethality,
      thereby suggesting essential roles for one or both of these enzymes during
      mammalian embryogenesis. Disruption of the Capn1 gene produced viable, fertile
      mice implying that either m-calpain could compensate for the loss of mu-calpain,
      or that the loss of m-calpain was responsible for death of Capn4-/- mice.
      RESULTS: To distinguish between the alternatives described above, we deleted an
      essential coding region in the mouse Capn2 gene in embryonic stems cells and
      transmitted this mutant allele through the mouse germline. Breeding of
      heterozygous animals failed to produce homozygous mutant live offspring or
      implanted embryos. A nested PCR genotyping protocol was established, and
      homozygous preimplantation mutant embryos were detected at the morula but not at
      the blastocyts stage. CONCLUSION: We conclude that homozygous disruption of the
      Capn2 gene results in pre-implantation embryonic lethality between the morula and
      blastocyst stage. This establishes that mu-calpain and m-calpain have distinct
      functions, and that m-calpain is vital for development of the preimplantation
      murine embryo.

PMID- 16433931
TI  - A reinforced merging methodology for mapping unique peptide motifs in members of
      protein families.
AB  - BACKGROUND: Members of a protein family often have highly conserved sequences;
      most of these sequences carry identical biological functions and possess similar
      three-dimensional (3-D) structures. However, enzymes with high sequence identity
      may acquire differential functions other than the common catalytic ability. It is
      probable that each of their variable regions consists of a unique peptide motif
      (UPM), which selectively interacts with other cellular proteins, rendering
      additional biological activities. The ability to identify and localize such UPMs
      is paramount in recognizing the characteristic role of each member of a protein
      family. RESULTS: We have developed a reinforced merging algorithm (RMA) with
      which non-gapped UPMs were identified in a variety of query protein sequences
      including members of human ribonuclease A (RNaseA), epidermal growth factor
      receptor (EGFR), matrix metalloproteinase (MMP), and Sma-and-Mad related protein
      families (Smad). The UPMs generally occupy specific positions in the resolved 3-D
      structures, especially the loop regions on the structural surfaces. These motifs
      coincide with the recognition sites for antibodies, as the epitopes of four
      monoclonal antibodies and two polyclonal antibodies were shown to overlap with
      the UPMs. Most of the UPMs were found to correlate well with the potential
      antigenic regions predicted by PROTEAN. Furthermore, an accuracy of 70% can be
      achieved in terms of mapping a UPM to an epitope. CONCLUSION: Our study provides
      a bioinformatic approach for searching and predicting potential epitopes and
      interacting motifs that distinguish different members of a protein family.

PMID- 16433932
TI  - Pharmacological profiles of opioid ligands at kappa opioid receptors.
AB  - BACKGROUND: The aim of the present study was to describe the activity of a set of
      opioid drugs, including partial agonists, in a human embryonic kidney cell system
      stably expressing only the mouse kappa-opioid receptors. Receptor activation was
      assessed by measuring the inhibition of cyclic adenosine mono phosphate (cAMP)
      production stimulated by 5 microM forskolin. Intrinsic activities and potencies
      of these ligands were determined relative to the endogenous ligand dynorphin and
      the kappa agonist with the highest intrinsic activity that was identified in this
      study, fentanyl. RESULTS: Among the ligands studied naltrexone, WIN 44,441 and
      dezocine, were classified as antagonists, while the remaining ligands were
      agonists. Intrinsic activity of agonists was assessed by determining the extent
      of inhibition of forskolin-stimulated cAMP production. The absolute levels of
      inhibition of cAMP production by each ligand was used to describe the rank order
      of intrinsic activity of the agonists; fentanyl = lofentanil > or = hydromorphone
      = morphine = nalorphine > or = etorphine > or = xorphanol > or = metazocine > or
      = SKF 10047 = cyclazocine > or = butorphanol > nalbuphine. The rank order of
      affinity of these ligands was; cyclazocine > naltrexone > or = SKF 10047 > or =
      xorphanol > or = WIN 44,441 > nalorphine > butorphanol > nalbuphine > or =
      lofentanil > dezocine > or = metazocine > or = morphine > hydromorphone >
      fentanyl. CONCLUSION: These results elucidate the relative activities of a set of
      opioid ligands at kappa-opioid receptor and can serve as the initial step in a
      systematic study leading to understanding of the mode of action of these opioid
      ligands at this receptor.

PMID- 16433933
TI  - Short-term elevation of intracranial pressure does neither influence duodenal
      motility nor frequency of bolus transport events: a porcine model.
AB  - BACKGROUND: Patients with traumatic brain injuries and raised intracranial
      pressure (ICP) display biphasic response with faster gastric emptying during the
      early stage followed by a prolonged gastric transit time later. While duodenal
      contractile activity plays a pivotal role in transpyloric transit we investigated
      the effects of raised intracranial pressure on duodenal motility during the early
      phase. In order to exclude significant deterioration of mucosal blood supply
      which might also influence duodenal motility, luminal microdialysis was used in
      conjunction. METHODS: During general anaesthesia, 11 pigs (32-37 kg, German
      Landrace) were instrumented with both a luminal catheter for impedancometry and a
      luminal catheter for microdialysis into the proximal duodenum. Additionally, a
      catheter was inserted into the left ventricle to increase the intracranial
      pressure from baseline up to 50 mmHg in steps of 10 mmHg each hour by injection
      of artificial cerebrospinal fluid. At the same time, duodenal motility was
      recorded continuously. Duodenal luminal lactate, pyruvate, and glucose
      concentrations were measured during physiological state and during elevated
      intracranial pressure of 10, 20, 30, 40, and 50 mmHg in six pigs. Five pigs
      served as controls. RESULTS: Although there was a trend towards shortened
      migrating motor cycle (MMC) length in pigs with raised ICP, the interdigestive
      phase I-III and the MMC cycle length were comparable in the groups. Spontaneous
      MMC cycles were not disrupted during intracranial hypertension. The mean
      concentration of lactate and glucose was comparable in the groups, while the
      concentration of pyruvate was partially higher in the study group than in the
      controls (p < 0.05). This was associated with a decrease in lactate to pyruvate
      ratio (p < 0.05). CONCLUSION: The present study suggests that a stepwise and
      hourly increase of the intracranial pressure of up to 50 mmHg, does not influence
      duodenal motility activity in a significant manner. A considerable deterioration
      of the duodenal mucosal blood flow was excluded by determining the lactate to
      pyruvate ratio.

PMID- 16433934
TI  - Memorable Medical Mentors: XV Alan F. Guttmacher (1898-1974).

PMID- 16433935
TI  - Skeletal consequences of hormone therapy discontinuance: a systematic review.
AB  - Although hormone therapy protects against bone loss after menopause, currently it
      is not recommended once menopausal symptoms have subsided. We reviewed randomized
      clinical trials to quantify bone loss after stopping hormone therapy and
      summarize treatment options for women who discontinue hormone treatment. We
      conducted a search of MEDLINE and EMBASE for randomized, controlled trials
      measuring bone mineral density (BMD) after hormone therapy discontinuation. Other
      known published and unpublished data were also included. Eleven studies fulfilled
      the search criteria. In each, bone loss was rapid after stopping hormone therapy,
      with BMD declines ranging from 2.3% to 6.2% in the first year. Increases in bone
      turnover markers also occurred rapidly when hormone therapy was stopped. Limited
      data addressing treatment after hormone therapy is stopped exist; only 2 studies
      specifically evaluated therapy to protect bone after hormone discontinuation.
      Taken together, these 2 studies demonstrate that alendronate produced significant
      increases relative to placebo in spine, hip, and total body BMD in women with low
      bone density who had discontinued hormone therapy within the past 3 months,
      preventing the rapid bone loss seen on discontinuation of hormone therapy. Among
      treatment options for preventing bone loss on discontinuation of hormone therapy
      for which randomized clinical trial data are available, alendronate prevented
      bone loss or increased bone density in postmenopausal women with low bone
      density. Women who are discontinuing hormone therapy should be counseled about
      potential bone loss and effective treatment options. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to state that
      discontinuation of replacement menopausal hormone therapy, which protects against
      bone loss, is not recommended after menopause symptoms have subsided; recall that
      it may accelerate bone loss; and explain that there is bone loss preventive
      treatment for women after discontinuation of hormone therapy.

PMID- 16433936
TI  - Polycystic ovary syndrome and its differential diagnosis.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder of reproductive-aged women.
      It affects between 3.4-6.8% of this population. Common clinical symptoms of PCOS
      include menstrual irregularities, hirsutism, and often obesity. Long-term
      sequelae include anovulatory infertility, endometrial carcinoma, and an increased
      risk for cardiovascular disease due to type II diabetes mellitus, dyslipidemia,
      and systolic hypertension. The diagnosis of PCOS is one of exclusion and is
      defined by the Rotterdam criteria which were established in 2004. However,
      several other endocrine disorders can closely resemble PCOS. It is important for
      practitioners to recognize and distinguish PCOS from other disorders in its
      differential. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.
      LEARNING OBJECTIVES: After completion of this article, the reader should be able
      to summarize the short-term reproductive and long-term metabolic consequences of
      polycystic ovary syndrome (PCOS), point out the importance of meeting the current
      criteria for diagnosis, and recall the recommended treatment related to the
      clinical presentation of the patient.

PMID- 16433937
TI  - Von Willebrand disease.
AB  - Von Willebrand disease (VWD), the most common inherited bleeding disorder,
      results from a deficiency of von Willebrand factor (VWF), a protein required for
      the normal adhesion of platelets to the site of injured endothelium and for
      preservation of factor VIII in the circulation. The prevalence of VWD has been
      reported to be as high as 1.3%. Among women with VWD, menorrhagia is the most
      common symptom, affecting 32% to 100%. Treatments that have been reported to
      control menorrhagia in these women include combined oral contraceptives, 1
      deamino-8-D-arginine vasopressin (DDAVP), tranexamic acid, and the levonorgestrel
      releasing intrauterine system. With the exception of nonsteroidal
      antiinflammatory drugs, any treatments effective in the treatment of menorrhagia,
      including hysterectomy, may be suitable. Besides menorrhagia, women with VWD
      appear to be at an increased risk of developing hemorrhagic ovarian cysts and
      possibly endometriosis. As they grow older, they may be more likely to manifest
      conditions that present with bleeding such as fibroids, endometrial hyperplasia,
      and polyps. During pregnancy, they may be at greater risk of miscarriage and
      bleeding complications, particularly delayed or secondary postpartum hemorrhage.
      Vaginal or vulvar hematomas, extremely rare in women without bleeding disorders,
      are not uncommon. Although women with VWD are at risk for the same obstetric and
      gynecologic problems that affect all women, they appear to be disproportionately
      affected by conditions that manifest with bleeding. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to recall that Von
      Willebrand Disease (VWD) is a common inherited disease, especially in women with
      menorrhagia; state that prophylaxis therapies against bleeding in pregnant and
      nonpregnant women are available; and explain that, despite prophylaxis,
      miscarriage and bleeding complications can still occur.

PMID- 16433938
TI  - Response bias and aging on a recognition memory task.
AB  - Response bias reflects the decision rule an individual uses when faced with
      uncertainty on recognition memory tasks. Recent studies indicate frontal regions
      may mediate response bias performance. One theory of aging also implicates
      frontal lobe contributions in age-related cognitive changes. This suggests that
      frontal lobe changes may mediate response bias in older adults. Consistent with
      this frontal aging hypothesis, we predicted that response bias would become more
      liberal with age. METHODS: Participants were 181 younger (30-49) and 112 older
      normal adults (75+) that were part of the California Verbal Learning Test-second
      edition (CVLT-2) normative sample (total n = 1078). We used parametric measures
      of discriminability and response bias provided by the CVLT-2 scoring program.
      Groups were similar in IQ and education. Multi-level regression models were
      created to examine the effects of moderating variables. The interaction between
      age and age group significantly predicted response bias. Post hoc analysis
      indicated that increasing age was associated with more liberal bias in the older
      but not in the younger group. In the light of reported relationships between
      frontal regions and both aging and response bias, we hypothesize that frontal
      changes may be the underlying mechanism explaining the increase in liberal
      response bias with age.

PMID- 16433939
TI  - The effects of distraction on prospective remembering following traumatic brain
      injury assessed in a simulated naturalistic environment.
AB  - The aim of this investigation was to assess deficits in prospective remembering
      following chronic traumatic brain injuries (TBI), under conditions of high and
      low distraction. We constructed a virtual shopping precinct from photographs,
      sounds, and video segments linked together. The street was divided into halves, a
      low distraction zone and a high distraction zone (with increased visual and
      auditory noise). Twenty persons with TBI (7 severe, 7 very severe, 6 extremely
      severe) and 20 matched controls completed ongoing and prospective memory tasks
      while "walking" along the street. In the ongoing task, participants were given
      ten errands to complete with a checklist accessible at any time. The prospective
      component required responding to three targets that appeared repeatedly. As
      predicted, the TBI group performed both the ongoing and the prospective
      components of the street task poorly compared with the controls and was more
      affected by distractions. The results suggest that the real-life deficits in
      memory skills reported by persons with TBI may become more apparent when
      remembering engages executive processes and that computer simulations can be used
      to construct sensitive measures of practical memory abilities.

PMID- 16433940
TI  - Neuropsychological changes following electrical injury.
AB  - The clinical presentation of electrical injury commonly involves physical,
      cognitive, and emotional complaints. Neuropsychological studies, including case
      reports, have indicated that electrical injury (EI) survivors may experience a
      broad range of impaired neuropsychological functions, although this has not been
      clarified through controlled investigation. In this study, we describe the
      neuropsychological test findings in a series of 29 EI patients carefully screened
      and matched to a group of 29 demographically similar healthy electricians.
      Participants were matched by their estimated premorbid intellectual ability.
      Multivariate analysis of variance was used to assess group differences in the
      following neuropsychological domains: attention and mental speed, working memory,
      verbal memory, visual memory, and motor skills. EI patients performed
      significantly worse on composite measures of attention/mental speed and motor
      skills, which could not be explained by demographic differences, injury
      parameters, litigation status, or mood disturbance. Results suggest that
      cognitive changes do occur in patients suffering from electrical injury.

PMID- 16433941
TI  - Decreased corpus callosum size in sickle cell disease: relationship with cerebral
      infarcts and cognitive functioning.
AB  - We assessed midsagittal corpus callosum size in sickle cell disease (SCD) and its
      relationship to lesion volume, lesion location, and cognitive functioning. Twenty
      eight children with SCD and 16 demographic controls completed magnetic resonance
      imaging (MRI) and neuropsychological testing. Corpus callosum (CC) size was
      smaller for children with silent infarcts (n = 8) or overt stroke (n = 8) than
      for those without visible infarcts (n = 12) or control participants. Lesion
      volume was a robust predictor of IQ and other cognitive scores; total CC size did
      not typically add explanatory power for these measures. The size of the rostral
      body of the CC, however, independently predicted measures of distractibility,
      speeded production, and working memory. Posterior CC size was also decreased
      among many of the children with SCD, even in the absence of visible infarcts in
      this region. Brain morphology appears to provide additional information about SCD
      related effects on the brain above and beyond visible infarcts.

PMID- 16433942
TI  - Neuropsychological and sensory gating deficits related to remote alcohol abuse
      history in schizophrenia.
AB  - Recent evidence suggests that changes in brain structure associated with alcohol
      abuse are compounded in individuals dually diagnosed with alcohol abuse and
      schizophrenia. To investigate the separate, and possibly interacting, effects of
      these diagnoses, an event-related brain potential (ERP) measure of auditory
      information processing (P50 sensory gating paradigm) and neuropsychological
      measures were administered to healthy control participants with either (1a) no
      history of alcohol abuse/dependence, or (1b) a remote history of alcohol
      abuse/dependence, and patients with schizophrenia with either (2a) no history of
      alcohol abuse/dependence, or (2b) a remote history of alcohol abuse/dependence.
      Schizophrenia was associated with impaired P50 sensory gating and poorer
      performance across neuropsychological scores compared to measurements in healthy
      control participants. Those with a positive alcohol history had impaired gating
      ratios in contrast to those with a negative alcohol history. There were additive
      effects of schizophrenia diagnosis and alcohol history for P50 sensory gating and
      for neuropsychological scores: attention, working memory, and behavioral
      inhibition. For executive attention and general memory there was an interaction,
      suggesting that the combination of schizophrenia and history of alcohol abuse
      results in greater impairment than that predicted by the presence of either
      diagnosis alone.

PMID- 16433944
TI  - A metacognitive contextual intervention to enhance error awareness and functional
      outcome following traumatic brain injury: a single-case experimental design.
AB  - Very few empirically validated interventions for improving metacognitive skills
      (i.e., self-awareness and self-regulation) and functional outcomes have been
      reported. This single-case experimental study presents JM, a 36-year-old man with
      a very severe traumatic brain injury (TBI) who demonstrated long-term awareness
      deficits. Treatment at four years post-injury involved a metacognitive contextual
      intervention based on a conceptualization of neuro-cognitive, psychological, and
      socio-environmental factors contributing to his awareness deficits. The 16-week
      intervention targeted error awareness and self-correction in two real life
      settings: (a) cooking at home; and (b) volunteer work. Outcome measures included
      behavioral observation of error behavior and standardized awareness measures.
      Relative to baseline performance in the cooking setting, JM demonstrated a 44%
      reduction in error frequency and increased self-correction. Although no
      spontaneous generalization was evident in the volunteer work setting, specific
      training in this environment led to a 39% decrease in errors. JM later gained
      paid employment and received brief metacognitive training in his work
      environment. JM's global self-knowledge of deficits assessed by self-report was
      unchanged after the program. Overall, the study provides preliminary support for
      a metacognitive contextual approach to improve error awareness and functional
      outcome in real life settings.

PMID- 16433943
TI  - Everyday action in dementia: evidence for differential deficits in Alzheimer's
      disease versus subcortical vascular dementia.
AB  - The relationship between dementia diagnosis and everyday action (e.g., meal
      preparation, grooming) is not well understood. This study examines differences
      between individuals diagnosed with vascular dementia (VaD; n = 25) versus
      Alzheimer's disease (AD; n = 23) on the Naturalistic Action Test (NAT; Schwartz
      et al., 2003), a performance-based measure that includes three tasks of
      increasing complexity. The percentage of task steps accomplished, number of
      errors, and performance times were recorded for each task. While the groups did
      not differ in dementia severity or overall impairment on the NAT, the VaD group
      committed more errors (3.3 vs. 1.6, p = 02). The VaD group also accomplished
      significantly fewer steps when salient distractor objects were present (74.0% vs.
      91.3%, p < .01). Correlations between NAT variables and neuropsychological tests
      suggest the executive control deficits associated with VaD may contribute to
      specific action difficulties, such as distractor interference and inefficient,
      error-prone action on complex tasks. In AD, everyday action may be negatively
      influenced by episodic memory failures. Thus, dementia diagnosis has relevance to
      everyday function.

PMID- 16433945
TI  - Reading ability mediates the relationship between education and executive
      function tasks.
AB  - Neuropsychological test results are affected by multiple factors, but usually age
      and education are the only variables by which norms are stratified. Some authors
      have questioned whether these variables alone are sufficient (e.g., Marcopulos et
      al., 1997; Manly et al., 2002), since such norms have lead to problems, such as
      poor specificity for African Americans on dementia screening devices (Fillenbaum
      et al., 1990). Recent research has shown that reading ability, a measure of
      educational quality, attenuated racial differences in test performance (Manly et
      al., 2002). We specifically examined whether reading ability would account for a
      greater amount of variance than education in executive function tests in a
      population traditionally subject to poor educational quality. Results determined
      that reading ability accounted for a significantly greater amount of variance
      than years of education for Letter-Number Sequencing, Similarities, COWA, Trail
      Making Test, and Coloured Progressive Matrices. Reading ability was found to
      significantly mediate the relationship between each of these tests and education.
      Animal naming appears to be least affected by educational quality or quantity.
      These findings hold implications for the interpretation of neuropsychological
      test results, especially in those exposed to substandard educational quality, and
      for the way that test norms are constructed.

PMID- 16433946
TI  - Neuropsychological detection of cognitive impairment: inter-rater agreement and
      factors affecting clinical decision-making.
AB  - The agreement between neuropsychologists identifying cognitive impairment (CI) in
      older adults was examined, as were factors influencing the classification
      process. Twenty four neuropsychologists in 18 study centers classified cases with
      or without CI after reviewing neuropsychological findings and other relevant
      information. All cases were participants in the third wave of the Canadian Study
      of Health and Aging, a study of CI in later life. For 117 randomly selected
      cases, a second neuropsychologist reviewed the same material and reclassified the
      cases. Cases given the same (concordant) or different (discordant)
      classifications were compared with respect to patient and rater characteristics.
      The inter-rater agreement was moderate (77.7% agreement, kappa = .49). On all
      measures of cognitive functioning, the concordant group without impairment
      obtained a higher mean score than the discordant group, and the discordant group
      obtained a higher mean score than the concordant group with impairment. For 5 out
      of 8 cognitive measures, the concordant group with impairment differed from the
      concordant group without impairment and the discordant group, but the latter two
      groups did not differ significantly. The findings are comparable to others in the
      field and highlight the need for neuropsychologists to further clarify procedures
      for identifying subtle, or mild, forms of cognitive impairment.

PMID- 16433947
TI  - Normative data for the Animal, Profession and Letter M Naming verbal fluency
      tests for Dutch speaking participants and the effects of age, education, and sex.
AB  - Previous research has indicated that performance on verbal fluency tests (VFTs)
      is influenced by language and/or culture. Consequently, normative VFT data for
      English-speaking people cannot be used for people for whom English is not their
      first language. The aim of the present study was to provide normative data for
      the Animal Naming, Profession Naming, and Letter M Naming (four-letter words
      beginning with the letter M) VFTs for Dutch-speaking populations, based on a
      large sample (N = 1856) of healthy men and women aged 24-81 years of different
      educational levels. The results showed that age affected the performance of all
      VFTs profoundly, but the age effect was not uniform: in the Profession and Letter
      M Naming VFTs, performance was stable in young adulthood but declined strongly
      after age 50. In contrast, in the Animal Naming VFT, performance appeared to
      decline linearly, starting early in life. Furthermore, males had higher scores
      than females on the Profession Naming VFT, and higher educated participants
      outperformed their lower educated counterparts on all three VFTs. Regression
      based normative data were prepared for the 3 VFTs, and the advantages of using a
      regression-based normative approach instead of a traditional normative approach
      are discussed.

PMID- 16433948
TI  - Altered adaptive but not veridical decision-making in substance dependent
      individuals.
AB  - Drug addiction is associated with impaired judgment in unstructured situations in
      which success depends on self-regulation of behavior according to internal goals
      (adaptive decision-making). However most executive measures are aimed at
      assessing decision-making in structured scenarios, in which success is determined
      by external criteria inherent to the situation (veridical decision-making). The
      aim of this study was to examine the performance of Substance Abusers (SA, n =
      97) and Healthy Comparison participants (HC, n = 81) in two behavioral tasks that
      mimic the uncertainty inherent in real-life decision-making: the Cognitive Bias
      Task (CB) and the Iowa Gambling Task (IGT) (administered only to SA). A related
      goal was to study the interdependence between performances on both tasks. We
      conducted univariate analyses of variance (ANOVAs) to contrast the decision
      making performance of both groups; and used correlation analyses to study the
      relationship between both tasks. SA showed a marked context-independent decision
      making strategy on the CB's adaptive condition, but no differences were found on
      the veridical conditions in a subsample of SA (n = 34) and HC (n = 22). A high
      percentage of SA (75%) also showed impaired performance on the IGT. Both tasks
      were only correlated when no impaired participants were selected. Results
      indicate that SA show abnormal decision-making performance in unstructured
      situations, but not in veridical situations.

PMID- 16433949
TI  - Vigilance and fatigue following traumatic brain injury.
AB  - Research findings have suggested that individuals with traumatic brain injury
      (TBI) show greater psychophysiological and subjective costs associated with
      performing vigilance tasks, but have not examined relationships with fatigue. The
      present study aimed to investigate vigilance and its relationship with subjective
      and objective fatigue measures. Forty-six TBI participants and 46 controls
      completed a 45-minute vigilance task. They also completed a subjective fatigue
      scale (the VAS-F) and a selective attention task before and after the vigilance
      task, and had their blood pressure (BP) monitored. TBI participants performed at
      a lower level on the vigilance task, but performed at a similar level across the
      duration of the task. Higher subjective fatigue ratings on the VAS-F were
      associated with more misses on the vigilance task for TBI participants. TBI
      participants showed greater increases in diastolic BP, and these were associated
      with greater increases in subjective fatigue ratings on the VAS-F. A subgroup of
      TBI participants showed a decline in performance on the vigilance task and also
      showed disproportionate increases in subjective fatigue. Findings provide support
      for the coping hypothesis, suggesting that TBI individuals expend greater
      psychophysiological costs in order to maintain stable performance over time, and
      that these costs are also associated with subjective increases in fatigue.

PMID- 16433950
TI  - Evaluating the utility of ICD-10 diagnostic criteria for postconcussion syndrome
      following mild traumatic brain injury.
AB  - The present study investigated the utility of the International Classification of
      Diseases and Related Health Problems, 10th edition (ICD-10) diagnostic criteria
      for postconcussion syndrome (PCS) symptoms by comparing symptom endorsement rates
      in a group of patients with mild traumatic brain injury (MTBI) to those of a
      noninjured control group at one month and three months post-injury. The 110 MTBI
      patients and 118 control participants were group-matched on age, gender, and
      education level. Seven of the nine self-reported ICD-10 PCS symptoms
      differentiated the groups at one month post-injury and two symptoms
      differentiated the groups at three months post-injury: symptom endorsement rates
      were higher in the MTBI group at both time periods. Fatiguing quickly and
      dizziness/vertigo best differentiated the groups at both time periods, while
      depression and anxiety/tension failed to differentiate the groups at either time
      period. Collectively, the ICD-10 PCS symptoms accurately classified the MTBI
      patients at one month post-injury, with the optimal positive test threshold of
      endorsement of five symptoms coinciding with a sensitivity and specificity of 73%
      and 61%, respectively. The ICD-10 PCS symptoms were unable to accurately classify
      the MTBI patients at three months post-injury.

PMID- 16433951
TI  - WAIS-III and WMS-III performance in chronic Lyme disease.
AB  - There is controversy regarding the nature and degree of intellectual and memory
      deficits in chronic Lyme disease. In this study, 81 participants with rigorously
      diagnosed chronic Lyme disease were administered the newest revisions of the
      Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III),
      and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had
      poorer Full Scale and Performance IQ's. At the subtest level, differences were
      restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme
      disease participants performed more poorly on Auditory Immediate, Immediate,
      Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among
      WMS-III subtests, however, differences were restricted to Logical Memory
      (immediate and delayed) and Family Pictures (delayed only), a Visual Memory
      subtest. Discriminant analyses suggest deficits in chronic Lyme are best
      characterized as a combination of memory difficulty and diminished processing
      speed. Deficits were modest, between one-third and two-thirds of a standard
      deviation, consistent with earlier studies. Depression severity had a weak
      relationship to processing speed, but little other association to test
      performance. Deficits in chronic Lyme disease are consistent with a subtle
      neuropathological process affecting multiple performance tasks, although further
      work is needed to definitively rule out nonspecific illness effects.

PMID- 16433953
TI  - Neural substrates of syntactic mapping treatment: an fMRI study of two cases.
AB  - Two patients (G01, J02) with chronic nonfluent aphasia and sentence production
      deficits received syntactic mapping treatment to improve sentence production. The
      patients had dramatically different outcomes in that improved syntax production
      generalized to nontreatment tasks for G01, but not for JO2. To learn how
      treatment influenced the neural substrates for syntax production, both patients
      underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) of
      sentence generation. G01 showed more robust activity posttreatment than
      pretreatment in Broca's area; ventral temporal activity decreased slightly from
      pre- to posttreatment. Comparison of J02's pretreatment and posttreatment images
      revealed little change, although activity was more diffuse pre- than
      posttreatment. Findings suggest that for G01, rehabilitation led to engagement of
      an area (Broca's area) used minimally during the pretreatment scan, whereas for
      J02, rehabilitation may have led to more efficient use of areas already involved
      in sentence generation during the pretreatment scan. fMRI findings are discussed
      in the context of sentence-production outcome and generalization.

PMID- 16433954
TI  - The effect of education and occupational complexity on rate of cognitive decline
      in Alzheimer's patients.
AB  - We explored the effect of education and occupational complexity on the rate of
      cognitive decline (as measured by the Mini-Mental State Examination) in 171
      patients with a confirmed Alzheimer's disease (AD) diagnosis. Complexity was
      measured as substantive complexity of work and complexity of work with data,
      people, and things. Average lifetime occupational complexity was calculated based
      on years at each occupation. Participants were followed for an average of 2.5
      years and 3.7 visits. In multivariate mixed-effects models, high education, high
      substantive complexity, and high complexity of work with data and people
      predicted faster rates of cognitive decline, controlling for age, gender, native
      language, dementia severity, and entry into the analyses at initial versus follow
      up testing. These results provide support for the concept of cognitive reserve
      according to which greater reserve may postpone clinical onset of AD but also
      accelerate cognitive decline after the onset.

PMID- 16433956
TI  - Efficacy of different Lysigin formulations in the prevention of Staphylococcus
      aureus intramammary infection in dairy heifers.
AB  - The objective was to compare the efficacy of two experimental Staphylococcus
      aureus mastitis bacterins and a currently marketed five-isolate-based Staph.
      aureus bacterin (Lysigin, Boehringer Ingelheim Vetmedica, Inc.) with unvaccinated
      controls. Forty-seven Holstein-Friesian heifers were randomly assigned to one of
      four groups such that Group 1 (n=11) received a three-isolate experimental
      bacterin, Group 2 (n=11) received a five-isolate experimental bacterin, Group 3
      (n=14) received Lysigin, and Group 4 (n=11) served as unvaccinated controls.
      Vaccinations were administered twice 28 d apart in late gestation. All groups
      were challenged with a heterologous strain of Staph. aureus (ATCC 29740) on days
      6, 7, and 8 of lactation. Mastitis score, somatic cell count (SCC), milk culture
      yield, and total daily milk yield data were collected before and after challenge.
      All 47 cattle developed a Staph. aureus IMI post-challenge with three animals in
      Group 1 and one animal in Group 3 clearing their Staph. aureus IMI by the end of
      the study. However, there was no evidence of a difference between vaccinates and
      control with regard to Staph. aureus clearance rates post-challenge (P> or
      =0.214). Cattle vaccinated with Lysigin had a lower mean duration of clinical
      mastitis and lower total mastitis score post-challenge than controls (P=0.045 and
      P=0.046, respectively). Overall, there was no evidence that any of the vaccinated
      groups had a lower mean SCC than control (P> or =0.148) for the tested study
      days. Likewise there was no evidence that vaccinates had greater milk yield than
      controls post-challenge (P=0.617). Hence, there was no evidence that the vaccines
      reliably prevented Staph. aureus IMI, but Lysigin showed benefit in reducing the
      clinical severity and duration of clinical disease post-challenge. Neither of the
      experimental bacterins appeared to perform better than Lysigin.

PMID- 16433955
TI  - Immunochemical quantification of heat denaturation of camel ( Camelus dromedarius
      ) whey proteins.
AB  - The major whey proteins IgG, serum albumin and alpha-lactalbumin were purified
      from camel milk using gel permeation and ion-exchange chromatography. Specific
      antisera against each of them were raised and used to quantify their heat
      denaturation in early or mature milk over a range of 60-90 degrees C for 10-60
      min using the single radial immunodiffusion technique. The heat denaturation
      midpoints for the mature milk heated 30 min were 67.2, 73.0 and 77.5 degrees C
      for IgG, albumin and alpha-lactalbumin respectively. The early milk was more
      sensitive to heat treatment with coagulation at low temperature and heat
      denaturation midpoints of 64.8, 71.6 and 72.6 degrees C respectively. This
      difference was related to the high IgG content of the early milk (12.6 mg/ml v.
      0.5 mg/ml for the mature milk) and stresses the importance of monitoring the IgG
      level of milk to assess the absence of colostrum.

PMID- 16433958
TI  - Oxytocin release and lactation performance in Syrian Shami cattle milked with and
      without suckling.
AB  - Oxytocin (OT) release and lactation performance in primiparous Syrian Shami cows
      were evaluated in response to two different machine milking regimes. Six cows
      were milked in the presence of the calves (PC) and subsequently suckled, whereas
      six cows were exclusively machine milked without the presence of their calves
      (WC) until day 91 post partum. Milk yield and milk constituents were determined
      weekly. The degree of udder evacuation was determined by the succeeding removal
      of residual milk. PC released OT during the milking process, whereas in WC no OT
      release was detected throughout the milking process. Consequently, the residual
      milk fraction was much lower in PC than in WC (11% v. 58%, P<0.05) and daily milk
      yield until day 91 post partum was higher in PC than in WC (12.6+/-0.3 v. 7.1+/
      0.4 kg, P<0.05). In conclusion, Syrian Shami cattle are not suitable to be
      exclusively machine milked without the presence of their calves.

PMID- 16433957
TI  - Molecular identification and typing of lactobacilli isolated from kefir grains.
AB  - Seventeen heterofermentative lactobacilli isolated from kefir grains were
      characterized by molecular methods. Bacterial isolates were identified by
      amplification of 16S rRNA gene and analysis by Amplified Ribosomal DNA
      Restriction Analysis (ARDRA), using the restriction enzymes Hae III, Dde I, and
      Hinf I. ARDRA analysis of lactobacilli isolates showed, for each enzyme used, a
      same banding pattern between the heterofermentative lactobacilli and the
      reference strains Lactobacillus kefir JCM 5818 and Lb. kefir ATCC 8007. Other
      reference lactobacilli and one homofermentative isolate showed differences in at
      least one of these patterns. The 16S-23S rRNA spacer region was also used to
      discriminate the bacterial isolates at the species level. The data obtained from
      the analysis of spacer region confirmed that sequencing of this genome region is
      a good tool for a reliable identification of members of Lb. kefir species.
      Genotyping of isolates was performed by Random Amplified Polymorphic DNA (RAPD
      PCR) analysis using M13, Coc, ERIC-2 and 1254 primers. Patterns obtained allowed
      the differentiation of isolates in three groups. The three clusters showed by
      RAPD-PCR analysis could be correlated with at least three different strains of
      Lb. kefir species in the group of heterofermentative lactobacilli isolates
      obtained from Argentinian kefir grains.

PMID- 16433959
TI  - Economic impacts of reduced milk production associated with epidemiological risk
      factors for Johne's disease on dairy operations in the USA.
AB  - An examination of the economic effects of epidemiologic risk factors for Johne's
      disease identified regional and herd size differences as having the greatest
      impact. Having dairy cows that were not born on the operation was the most
      important factor over which individual producers had the most immediate control.
      Economic consequences associated with using multiple-cow-maternity housing and
      multiple-preweaned-calf housing were not statistically significant. Economic
      welfare analysis was applied, and the GUM Workbench was used to analyse
      uncertainties in the estimates of the economic impacts.

PMID- 16433960
TI  - Calcium-enriched casein phosphopeptide stimulates release of IL-6 cytokine in
      human epithelial intestinal cell line.

PMID- 16433961
TI  - Purification and characterization of chymosin and pepsin from kid.
AB  - The objective of this work was to study the characteristics of the gastric
      aspartic proteinases chymosin and pepsin which are constituents of the kid
      rennet. The two enzymes were extracted from abomasal tissue of one kid from a
      local indigenous breed, separated from each other by DEAE-cellulose
      chromatography and then were purified by gel filtration and anion-exchange
      chromatography. The molecular weights of the purified kid chymosin and pepsin as
      determined by gel filtration were 36 kDa and 40 kDa respectively. The isoelectric
      point of kid chymosin was as multiple forms of 3-6 zones at pH 4.6-5.1, while
      that of kid pepsin was at pH < or =3.0. Kid pepsin contained 0.37 molecules
      phosphorous per molecule and was totally inhibited by 5 muM pepstatin A, being
      more sensitive than kid chymosin. Both enzymes were almost equally as proteolytic
      as calf chymosin on total casein at pH 5.6. Kid pepsin activity was more pH and
      temperature dependent than kid chymosin activity. In comparison with the calf
      chymosin temperature sensitivity, the order of increased sensitivity was: calf
      chymosin <kid chymosin <kid pepsin.

PMID- 16433962
TI  - Modelling of sensory and instrumental texture parameters in processed cheese by
      near infrared reflectance spectroscopy.
AB  - This study investigated the application of near infrared (NIR) reflectance
      spectroscopy to the measurement of texture (sensory and instrumental) in
      experimental processed cheese samples. Spectra (750 to 2498 nm) of cheeses were
      recorded after 2 and 4 weeks storage at 4 degrees C. Trained assessors evaluated
      9 sensory properties, a texture profile analyser (TPA) was used to record 5
      instrumental parameters and cheese 'meltability' was measured by computer vision.
      Predictive models for sensory and instrumental texture parameters were developed
      using partial least squares regression on raw or pre-treated spectral data.
      Sensory attributes and instrumental texture measurements were modelled with
      sufficient accuracy to recommend the use of NIR reflectance spectroscopy for
      routine quality assessment of processed cheese.

PMID- 16433963
TI  - Acceleration of proteolysis during ripening of Cheddar-type cheese using of a
      streptokinase-producing strain of Lactococcus.

PMID- 16433964
TI  - Increased remineralization of tooth enamel by milk containing added casein
      phosphopeptide-amorphous calcium phosphate.
AB  - Casein phosphopeptide amorphous calcium phosphate nano-complexes (CPP-ACP) in
      chewing gum, lozenges and mouthrinses have been shown to re-mineralize enamel
      subsurface lesions in human in situ experiments. The aim of this double-blind,
      randomized clinical study was to investigate the capacity of CPP-ACP added to
      bovine milk to re-mineralize enamel subsurface lesions in situ. Ten subjects
      drank milk containing either 2.0 or 5.0 g CPP-ACP/l or a control milk whilst
      wearing removable appliances with enamel slabs containing subsurface
      demineralized lesions. Each 200 ml milk sample was consumed once a day for each
      weekday over three consecutive weeks. After each treatment and one weeks rest the
      subjects crossed over to the other treatments. At the completion of the
      treatments the enamel slabs were removed and remineralization determined using
      microradiography and microdensitometry. The results demonstrated that all three
      milk samples re-mineralized enamel subsurface lesions. However, the milk samples
      containing CPP-ACP produced significantly greater remineralization than the
      control milk. The re-mineralizing effect of CPP-ACP in milk was dose-dependent
      with 2.0 and 5.0 g CPP-ACP/l producing an increase in mineral content of 70 and
      148%, respectively, relative to the control milk. The differences in
      remineralization following exposure to the three milk samples were all
      statistically significant (P<0.001). In conclusion, this study shows that the
      addition of 2.0-5.0 g CPP-ACP/l to milk substantially increases its ability to re
      mineralize enamel subsurface lesions.

PMID- 16433966
TI  - Isolation and identification of some major peptides in the ethanol-soluble
      fraction of the pH 4.6-soluble extract from Manchego cheese.

PMID- 16433965
TI  - pH-Dependent behaviour of soluble protein aggregates formed during heat-treatment
      of milk at pH 6.5 or 7.2.
AB  - The pH-dependent behaviour of soluble protein aggregates produced by the pre
      heating of reconstituted skim milk at 90 degrees C for 10 min was studied, in
      order to understand the role of these aggregates in acid gelation of heated milk.
      The following milk samples were prepared: (1) control (unheated reconstituted
      milk, pH 6.5); (2) milk heat-treated at pH 6.5 (mHtd6.5) and (3) milk heat
      treated at pH 7.2 (mHtd7.2). They were centrifuged and the supernatants (SPNT 1)
      pH-adjusted to yield a series of pH values ranging from 6.5 or 7.2 to 4.6 using
      HCl at 20 degrees C or GDL at 20 and 38 degrees C. pH-Adjusted SPNTs 1 were re
      centrifuged. The resulting supernatants (SPNTs 2) were analysed by OD (at 600 and
      280 nm) and SDS-PAGE in order to characterise proteins still soluble as a
      function of pH. Particle size in SPNTs 1 was analysed by Steric Exclusion
      Chromatography. The OD600 nm revealed that during acidification soluble casein in
      both control and heat-treated samples exhibits variations in its optical
      properties or size as previously shown with micellar casein. In heat-treated
      samples, soluble casein and heat-induced covalent soluble aggregates precipitate
      at the same pH value. A progressive acidification of the soluble phase did not
      separate them. Increasing the temperature of acidification from 20 to 38 degrees
      C resulted in an increase in the precipitation pH of the proteins. However choice
      of acidifier did not have a significant effect on OD profiles. The soluble
      covalent aggregates from mHtd7.2 were smaller, more numerous, and had a higher
      content of kappa-casein than mHtd6.5. Both types of aggregates began to
      precipitate at the same pH value but precipitation occurred over a narrower pH
      range for soluble aggregates prepared from mHtd7.2. This may explain the higher
      gelation pH of mHtd7.2 compared with mHtd6.5.

PMID- 16433968
TI  - Phenotypic study on total and partial lifetime traits for dairy ewes.
AB  - A data file on 36,396 lactations was used to determine the strength of the
      phenotypic relationship between productive, reproductive and lifespan traits for
      7935 Spanish Churra ewes. These ewes first lambed between 1989 and 1997 and
      belonged to 23 flocks. The study took into account four lifespan traits
      (lifetime, productive life, useful life and lifetime score), three productive
      traits (total milk yield produced during lifetime, lambs weaned during ewe
      lifetime and total revenues from sold milk and weaned lambs during lifetime) and
      two reproductive traits (age at first lambing and mean interval between
      successive lambings). Moreover, milk yield and revenues from sold milk and weaned
      lambs were calculated per day of lifetime, productive life and useful life.
      Partial lifespan traits were considered for the first three parities. The model
      included flock, birth year within flock and season of birth of the ewe as fixed
      effects. The first two effects contributed significantly to variation in all
      traits, while season significantly affected lifespan traits, productive traits
      and age at first lambing. Milk production level was added to the model for
      lifespan traits only. It significantly contributed to explaining the variation in
      all lifespan traits with high percentage of variance explained averaging 14.91%.
      Lifetime averaged 2324 d. Productive life accounted for 57% of lifetime while
      useful life represented 50% of productive life. Age at first lambing averaged 622
      d and average days dry during lifetime was 560. During lifetime, ewes gave an
      average of 4.6 parities, 6.5 weaned lambs and 636 l of milk. Average revenue from
      milk and lambs during lifetime was 673 euros. Milk/day of lifetime, productive
      life and useful life averaged 0.26, 0.51 and 0.93 l, respectively. The
      corresponding per-day revenues from sold milk and weaned lambs were, 0.27 euros,
      0.55 euros and 1.01 euros, respectively. Lifespan and productive traits had
      strong relationships (rp among these traits ranged between 0.75 and 0.95). Two
      parity and three-parity per-day milk yield had moderately high correlation (0.70
      0.83) with total lifetime per-day milk yield traits. Therefore, good use of these
      traits would be helpful in determining best individuals early in life.

PMID- 16433967
TI  - Pressurisation of raw skim milk and of a dispersion of phosphocaseinate at 9
      degrees C or 20 degrees C: effects on the distribution of minerals and proteins
      between colloidal and soluble phases.
AB  - The effects of high pressure treatments (100-300 MPa; 15 min; 9 degrees C or 20
      degrees C) on the distribution of minerals and proteins of raw skim milk (RSM)
      and of a dispersion of industrial phosphocaseinate (PC) were studied after
      separation of the micellar and soluble phases by ultracentrifugation (UCF).
      Whatever the temperature of high pressure treatments, the pressure-induced
      dissociation of the casein micelles was accompanied by calcium (Ca), phosphorus
      (P) and casein release from the micelles. The released Ca and P were or became
      bound to soluble proteins since progressive increases in Ca and P concentrations
      were observed in the UCF supernatants of RSM and of the PC dispersion but not in
      the ultrafiltrates from these UCF supernatants (free of soluble proteins).
      Simultaneously, alpha(S1-), alpha(S2-), beta- and kappa-caseins were
      progressively released from the micelles, as seen by electrophoretic analysis.
      The pressure-induced solubilisation of alpha(S1-) and alpha(S2-)caseins,
      essentially located in the core of the micelles, suggests that high pressure de
      stabilized micelles including their internal structure.

PMID- 16433969
TI  - Accuracy of simplified sampling procedures for estimating milk composition in
      dairy ewes.
AB  - Simplified designs of milk-composition recording, based on information from a
      single monthly milking, adjusted or not for interval between milkings and for
      milk yield, were simulated and evaluated for 2553 ewe-test-day records belonging
      to 155 lactations of Churra dairy ewes. Accuracy of simplified methods was
      evaluated by comparing estimated trait values (fat, protein, casein and total
      solid yields) with those observed both in a reference plan, where the two daily
      milkings were recorded at weekly intervals (A1), and in the official A4 milk
      recording (monthly records of the two daily milkings). Trait yields per lactation
      were estimated and adjusted to the only milking period (days in milk 30-120).
      Estimates of milk component traits were less precise when monthly designs,
      including the A4 design, were compared with a weekly sampling of both a.m. and
      p.m. milkings, with fat yield being the most difficult trait to estimate. All
      options with one daily milking every month were more accurate when the
      corresponding plan was based on, or began with, the a.m. milking. Adjustment for
      the preceding interval between milkings or milk yield did not improve sampling
      accuracy. The design alternating a.m. and p.m. milkings every month, without
      adjustment, is suggested for recoding milk component traits in dairy ewes.

PMID- 16433970
TI  - The occurrence and nature of electrochemical activity in milk from a herd of
      dairy cows.
AB  - Amperometric sensors may be used in milk analysis but electrochemical
      interference from compounds other than the analyte is an on-going problem. A
      survey was made of the level of electrochemical activity (potential interference)
      in milk from a herd of dairy cows grazing on summer pasture. It was a ubiquitous
      feature of the aqueous phase of whey and de-proteinized milk over about 3 months.
      The nature of the interference was studied by differential pulse voltammetry and
      responses to ascorbic acid oxidase and uricase. The principal source of
      interference appeared to be uric acid.

PMID- 16433971
TI  - Influence of high hydrostatic pressure on the proteolysis of beta-lactoglobulin A
      by trypsin.
AB  - This work describes the effect of the hydrolysis time and pressure (0.1-400 MPa)
      on the proteolysis of beta-lactoglobulin A (beta-lg A) with trypsin, either
      conducting hydrolysis of beta-lg under pressure or hydrolysing beta-lg that was
      previously pressure treated. Pressurisation, before or during enzyme treatments,
      enhanced tryptic hydrolysis of beta-lg. Trypsin degraded pressure-modified beta
      lg and pressure-induced beta-lg aggregates, favouring proteolysis to the
      intermediate degradation products: (Val(15)-Arg(40)), (Val(41)-Lys(69))S
      S(Leu(149)-Ile(162)) and (Val(41)-Lys(70))S-S(Leu(149)-Ile(162)). These were
      further cleaved at the later stages of proteolysis to yield: (Val(15)-Tyr(20)),
      (Ser(21)-Arg(40)), (Val(41)-Tyr(60)), (Trp(61)-Lys(69))S-S(Leu(149)-Ile(162)) and
      (Trp(61)-Lys(70))S-S(Leu(149)-Ile(162)). Particularly, in the tryptic
      hydrolysates of pre-pressurized beta-lg, two other fragments linked by disulphide
      bonds: (Lys(101)-Arg(124))S-S(Leu(149)-Ile(162)) and (Tyr(102)-Arg(124))S
      S(Leu(149)-Ile(162)), were found. These corresponded to rearrangement products
      induced by SH/SS exchange between the free thiol group of Cys(121) and Cys(160),
      that normally forms the disulphide bond Cys(66)-Cys(160). In the light of these
      results, structural modifications of beta-lg under high pressure are discussed.

PMID- 16433996
TI  - [Role of shear stress in atherosclerosis and restenosis after coronary stent
      implantation].

PMID- 16433997
TI  - [The heart, sleep and respiration].

PMID- 16433998
TI  - [Consensus on the interpretation of exercise echocardiography: still awaited].

PMID- 16433999
TI  - [Usefulness of clinical profiling and exercise testing in the prognostic
      assessment of patients admitted with chest pain but without high-risk criteria].
AB  - INTRODUCTION AND OBJECTIVES: Few data are available on the outcome of patients
      admitted to hospital with suspected acute coronary syndrome who have no high-risk
      factors and who undergo exercise testing before discharge. Our objectives were to
      investigate outcomes in this group of patients and to determine whether clinical
      history-taking or exercise testing can help to predict outcome. PATIENTS AND
      METHOD: The study population comprised 449 patients admitted to hospital with
      chest pain suggestive of acute coronary syndrome. All were judged to be at a low
      risk of subsequent events (i.e., none had ischemic ECG changes or an elevation in
      troponin level). They underwent treadmill exercise testing before discharge,
      after an observation period of at least 12 hours. Exercise testing was performed
      after clinical evaluation based on an algorithm involving troponin-T level and
      resting ECG. The median follow-up duration was 479 days. The single combined
      endpoint was defined as cardiac death, or hospital admission for nonfatal acute
      myocardial infarction or unstable angina. RESULTS: Adverse events occurred in 44
      (10%) of the 449 patients. A high event rate was associated with four clinical
      features (i.e., age > or =65 years, diabetes, previous acute myocardial
      infarction, and typical chest pain) and with a positive result on exercise
      testing. CONCLUSIONS: Adverse events after discharge are not infrequent in
      patients admitted to hospital with suspected acute coronary syndrome and a low
      risk profile. Both the patient's clinical characteristics and exercise test
      results should be taken into account in accurately determining prognosis.

PMID- 16434000
TI  - [Influence of shear stress on in-stent restenosis: in vivo study using 3D
      reconstruction and computational fluid dynamics].
AB  - INTRODUCTION AND OBJECTIVES: Local factors may influence neointimal proliferation
      following conventional stent implantation. In this study, the relationship
      between wall shear stress and luminal loss after coronary stenting was assessed
      using a combination of angiography, intravascular ultrasound, and computational
      fluid dynamics. PATIENTS AND METHOD: Seven patients with de novo right coronary
      lesions treated with conventional (i.e., bare metal) stents were included.
      Realistic three-dimensional geometric reconstructions were generated offline from
      angiographic and intravascular ultrasound data both immediately after stenting
      and at 6-month follow-up. A finite-volume model was used to calculate local wall
      shear stress within the stent and 4 mm proximally and distally to the stent. The
      mean coronary ostium entry flow velocity was assumed to be 25 cm/s in all cases.
      RESULTS: The mean neointimal thickness was 0.29 (0.21) mm. In five cases, weak
      negative correlations between wall shear stress and neointimal thickness were
      found: maximum r value = -0.34, minimum r value = -0.11 (P < .001). The
      neointimal thickness in segments in which the level of wall shear stress was in
      the lowest quartile was greater than that in segments in which it was in highest
      quartile, at 0.34 (0.21) mm and 0.27 (0.24) mm (P < .001) for quartiles 1 and 4,
      respectively. CONCLUSIONS: Low wall shear stress after stenting favors neointimal
      proliferation both within the stent and at the stent's edges.

PMID- 16434001
TI  - [Prevalence of obstructive sleep apnea syndrome in patients with sick sinus
      syndrome].
AB  - INTRODUCTION AND OBJECTIVES: Sleep apnea-hypopnea syndrome (SAHS) has been
      associated with different cardiovascular diseases. It may even be implicated in
      the pathophysiology of sick sinus syndrome (SSS). However, the precise
      relationship between the two syndromes is still unknown. We investigated the
      prevalence of SAHS in patients diagnosed with SSS. PATIENTS AND METHOD: Between
      June 2002 and December 2004, 38 consecutive patients who were diagnosed with SSS
      by 24-hour Holter monitoring were studied prospectively in our institution. All
      patients were asked about symptoms of SAHS, and underwent polysomnography out of
      hospital using a validated monitor. RESULTS: The patients' mean age was 67 (10)
      years, 68% were male, and 58% were hypertensive. Holter monitoring demonstrated a
      maximum heart rate of 87 (6) beats/min, a minimum of 35 (3) beats/min, and a mean
      of 48 (3) beats/min. Some 24 (63%) patients required pacemaker implantation
      because of symptomatic SSS. Overall, 39% of patients had symptoms suggestive of
      SAHS (i.e., an Epworth index or EI>9). Polysomnography showed that only 13% of
      patients had a normal apnea-hypopnea index (AHI) and that 31.6% (95% CI, 16.8%
      46.4%) had SAHS (i.e., AIH>10 and EI>9). CONCLUSIONS: Given that the prevalence
      of SAHS in the general population is around 3%, our results indicate that it is
      ten-fold higher in patients with SSS than in the general population. This
      observation indicates that there may be a relationship between the two syndromes.

PMID- 16434002
TI  - [Agreement between centers on the interpretation of exercise echocardiography].
AB  - INTRODUCTION AND OBJECTIVES: A low-to-moderate level of agreement on the
      interpretation of dobutamine echocardiography has been reported, but there are no
      similar findings on exercise echocardiography. The objectives of this study were
      to assess the level of agreement between centers on the use of exercise
      echocardiography and to evaluate the accuracy of the technique when used in a
      blinded manner. PATIENTS AND METHOD: Six institutions with experience in exercise
      echocardiography each sent 25 study results to the other centers. Of these, 15
      were positive or negative studies on consecutive patients undergoing coronary
      angiography, and 10 were on non-diabetic patients who had non-coronary chest pain
      or were asymptomatic and whose pretest probability of coronary artery disease was
      < 10%. Each institution evaluated 150 studies: 125 blinded and 25 of their own
      with knowledge of clinical data. RESULTS: For 116 patients (78%), four or more of
      the five centers blindly evaluating each study agreed with the positive or
      negative result. The average kappa coefficient was 0.48 (intercenter range 0.45
      0.52). The percentage agreement was higher with three-vessel disease (93%, range
      85%-95%), with left anterior descending coronary artery disease (83%, range 80%
      86%), and when the referring institution reported baseline dyssynergy (86%, range
      82%-90%), dyssynergy in left anterior descending coronary artery territory (81%,
      range 76%-84%), or a peak wall motion score index > 1.50 (88%, range 85%-90%).
      When the technique was used blinded to detect > or = 50% coronary narrowing in >
      or = 1 vessel, its sensitivity, specificity and accuracy were 68%, 66% and 67%,
      respectively, with wide variability between centers. CONCLUSIONS: There was
      moderate agreement between centers on the interpretation of exercise
      echocardiography. When used blinded, the technique's accuracy was lower than that
      reported when clinical data is known.

PMID- 16434003
TI  - [Usefulness of pulsed Doppler tissue imaging in the early detection of diastolic
      myocardial abnormalities in first-degree relatives of patients with familial
      hypertrophic cardiomyopathy].
AB  - INTRODUCTION AND OBJECTIVES: Doppler tissue imaging (DTI) enables regional
      myocardial function to be assessed irrespective of preload. Our aim was to
      determine the usefulness of DTI in healthy relatives of patients with familial
      hypertrophic cardiomyopathy. PATIENTS AND METHOD: We studied 47 first-degree
      relatives of patients with familial hypertrophic cardiomyopathy (group GI) and 47
      normal subjects (group GII). Echocardiographic studies, including DTI, were
      performed in both groups. DTI was used to measure myocardial velocities during
      systole (S'), early diastole (E') and atrial contraction (A') at the mitral
      annulus, septum, and tricuspid annulus. Isovolumic relaxation and contraction
      times were corrected for heart rate. With DTI assessment of regional diastolic
      myocardial function and use of the E'/A' ratio, normal (i.e., E'/A'>1) and
      abnormal (i.e., E'/A'<1) diastolic function could be distinguished. RESULTS:
      There were no abnormalities in regional diastolic function in group GII (right
      E'/A' 1.78 (0.58), septum E'/A' 2.03 (0.53), and left E'/A' 2.55 (0.80). However,
      in group GI, two subgroup could be distinguished using E'/A' ratio values: group
      GIa comprised 37 first-degree relatives with normal diastolic function (right
      E'/A' 1.8 (0.44), septum E'/A' 2.07 (0.41), and left E/A 2.35 (0.6) who did not
      differ significantly from control subjects, and group GIb comprised 10 first
      degree relatives with abnormal right diastolic function (right E'/A' 0.70 (0.28),
      P<.001) but with less significant differences at the septum (1.57 (0.49), P<.01)
      and mitral annulus (1.85 (0.53), P<.01). CONCLUSIONS: In 10 of 47 (21.3%) first
      degree relatives of patients with familial hypertrophic cardiomyopathy, DTI
      enabled the detection of ventricular diastolic abnormalities, which were more
      evident in the right ventricle. They could be a preclinical manifestation of
      disease.

PMID- 16434004
TI  - [C-reactive protein and interleukin-6 serum levels increase as Chagas disease
      progresses towards cardiac failure].
AB  - INTRODUCTION AND OBJECTIVES: Chagas disease is the most common cause of
      myocarditis in Latin America, including Venezuela. Some 25% of patients progress
      to chronic chagasic cardiomyopathy, which is characterized by heart failure and
      arrhythmias. The serum levels of C-reactive protein (CRP) and interleukin-6 (IL
      6) have prognostic value in non-chagasic cardiopathy. The goal of this study was
      to investigate the relationship between the serum levels of CRP and IL-6 and the
      developmental stage of Chagas disease. PATIENTS AND METHOD: The study included 64
      Chagas disease patients (34 female and 30 male; age 62.2 [1.7] years) and 20
      healthy individuals (10 of each sex; age 50.4 [2.7] years). Clinical
      investigations included echocardiography and measurement of CRP and IL-6 serum
      levels using ELISAs. Chagas disease patients were graded according to Carrasco et
      al 1994 classification. Patients with ischemic cardiopathy, liver disease,
      autoimmune disease, a systemic inflammatory condition, immunosuppression, cancer,
      pericarditis, or endocarditis were excluded. RESULTS: Multiple regression
      analysis demonstrated an association between Chagas disease developmental stage
      and the serum IL-6 level. The serum CRP level increased during only the most
      advanced phase of the disease. In addition, a high left ventricular mass index
      was associated with a high IL-6 level and male sex. CONCLUSIONS: IL-6 and CRP
      serum levels could be of prognostic value in assessing Chagas disease progression
      because there are significant correlations between elevated levels and the
      deterioration of cardiac function.

PMID- 16434005
TI  - [Assessment of progression and regression of coronary atherosclerosis by
      intravascular ultrasound. A new paradigm shift?].
AB  - Intravascular ultrasound (IVUS) has emerged as a powerful imaging modality for
      the assessment of the arterial wall and it's response to the accumulation of
      atherosclerotic plaque. The ability to image the coronary arteries on a serial
      basis provides a unique opportunity for IVUS to monitor the impact that potential
      anti-atherosclerotic strategies exert on plaque burden. As a result, studies
      incorporating serial IVUS imaging as the primary endpoint have demonstrated that
      therapeutic strategies that modify LDL, HDL and blood pressure in patients with
      established coronary artery disease can have a profound impact on the progression
      of atherosclerotic plaque. This heralds a paradigm shift that emphasizes plaque
      regression as a potential target in the development of preventive strategies.

PMID- 16434006
TI  - [Cor triatriatum in adults: intracardiac echocardiography].

PMID- 16434007
TI  - [Analysis of head-up tilt test responses in patients suffering from syncope and
      high blood pressure].
AB  - We studied the difference in head-up tilt test responses between patients
      suffering from syncope who had hypertension and those who did not. A total of 338
      consecutive patients with syncope underwent head-up tilt testing in our
      department from January 2003 to October 2004. Of these, 243 did not have
      hypertension (group A), whereas 95 did (group B). There were significant
      differences between the groups in age (P=.0001), sex (P=.048), timing of syncope
      development (P=.0001), and prevalence of diabetes mellitus (P=.0001). The head-up
      tilt test gave positive results in 168 patients (69.1%) in group A and in 63
      (66.3%) in group B (P=.6; NS). There was no significant difference between the
      groups in the proportion of positive responses that occurred in either the
      baseline or nitroglycerin-enhanced phase of the test (P=.673; NS), nor in the
      time to onset of syncope in either phase (P=.69; NS, and P=.28; NS,
      respectively). However, there was a significant difference in the type of
      response (vasodepressor response, 33% in group A versus 49% in group B, P=.01).
      In the multivariate analysis, no independent variable was found to be associated
      with the result of the head-up tilt test.

PMID- 16434008
TI  - [Subaortic stenosis more than twenty years after surgical repair of a partial
      atrial septal defect in an adult].
AB  - Subaortic stenosis after surgical correction of a partial atrioventricular septal
      defect is uncommon. When it occurs, it is usually diagnosed 6-8 years after early
      surgical repair in childhood. We present a female patient who underwent mitral
      valve cleft repair and closure of a partial atrial septal defect with a Teflon
      patch at the age of 48 years. Twenty-two years later, she presented with severe
      subaortic stenosis that required surgical repair. We analyze the intracardiac
      morphological factors associated with the development of late subaortic stenosis.
      We recommend long-term follow-up, even after surgical repair in adults.

PMID- 16434009
TI  - [Magnetic resonance imaging evidence of the effectiveness of combination
      chelation therapy in iron overload cardiomyopathy].
AB  - Heart failure secondary to iron overload is the main cause of death in patients
      with beta-thalassemia major. Combination therapy with deferoxamine and
      deferiprone has been shown to be more effective than either drug used alone in
      patients with beta-thalassemia major and symptomatic cardiomyopathy. Although
      monitoring the response to chelation therapy is usually carried out by indirect
      measurement of the serum ferritin level or by direct determination of tissue iron
      content in biopsy specimens, magnetic resonance imaging (MRI) seems to be useful
      for noninvasive qualitative and quantitative assessment of iron deposition. We
      present a case in which the efficacy of double chelation therapy in a patient
      with beta-thalassemia major and heart failure was demonstrated by MRI.

PMID- 16434010
TI  - [Transcatheter closure of patent foramen ovale in patients with platypnea
      orthodeoxia].
AB  - Platypnea-orthodeoxia is a rare syndrome characterized by the occurrence of
      dyspnea and hypoxemia on adoption of an upright posture (i.e., orthodeoxia) and
      by the absence of symptoms and hypoxemia in decubitus. This syndrome is
      frequently related to patent foramen ovale and right-to-left shunting. We
      describe two patients in whom patent foramen ovale with right-to-left shunting
      was observed on transthoracic and transesophageal echocardiography and who had
      platypnea-orthodeoxia in the absence of pulmonary disease. They underwent
      transcatheter closure using an Amplatz device. The echocardiographic diagnosis
      and closure procedure are discussed. These case reports demonstrate that closure
      of patent foramen ovale is an effective treatment for platypnea-orthodeoxia.

PMID- 16434011
TI  - [Left ventricular free wall rupture after percutaneous coronary reperfusion
      following acute myocardial infarction].

PMID- 16434012
TI  - Is an armed society a polite society? Guns and road rage.
AB  - BACKGROUND: While concerns about road rage have grown over the past decade,
      states have made it easier for motorists to carry firearms in their vehicles. Are
      motorists with guns in the car more or less likely to engage in hostile and
      aggressive behavior? METHODS: Data come from a 2004 national random digit dial
      survey of over 2,400 licensed drivers. Respondents were asked whether, in the
      past year, they (1) made obscene or rude gestures at another motorist, (2)
      aggressively followed another vehicle too closely, and (3) were victims of such
      hostile behaviors. RESULTS: Seventeen percent admitted making obscene or rude
      gestures, and 9% had aggressively followed too closely. Forty-six percent
      reported victimization by each of these behaviors in the past year. Males, young
      adults, binge drinkers, those who do not believe most people can be trusted,
      those ever arrested for a non-traffic violation, and motorists who had been in a
      vehicle in which there was a gun were more likely to engage in such forms of road
      rage. CONCLUSION: Similar to a survey of Arizona motorists, in our survey, riding
      with a firearm in the vehicle was a marker for aggressive and dangerous driver
      behavior.

PMID- 16434013
TI  - In-depth investigation of escalator riding accidents in heavy capacity MRT
      stations.
AB  - In 2000, the accident rate for escalator riding was about 0.815 accidents per
      million passenger trips through Taipei Metro Rapid Transit (MRT) heavy capacity
      stations. In order to reduce the probability and severity of escalator riding
      accidents and enhance the safety of passengers, the Drury and Brill model [Drury,
      C.G., Brill, M., 1983. Human factors in consumer product accident investigation.
      Hum. Factors 25 (3), 329-342] for in-depth investigation was adopted to analyze
      the 194 escalator riding accidents in terms of victim, task, product and
      environment. Prevention measures have been developed based on the major causes of
      accidents and other related contributing factors. The results from the analysis
      indicated that the majority of the escalator riding accidents was caused by
      passengers' carrying out other tasks (38 cases, including carrying luggage 24
      cases, looking after accompany persons 9 cases, and 5 others), loss of balance
      (26 cases, 13.4%), not holding the handrail (20 cases, 10.3%), unhealthy
      passengers (18 cases, 9.3%), followed by people struck by other passenger (16
      cases, 8.2%). For female passengers aged 15-64 years, their rushing for trains
      accidents could have been prevented by wearing safer footwear or by appropriate
      signing being provided indicating the location and traveling direction of
      escalators. Female passengers aged 65 years and above whose accidents were caused
      by loss of balance, should be encouraged to take the elevator instead. To prevent
      entrapment injuries, following a stricter design code can be most effective.
      Further in-depth accident investigation is suggested to cover the activity of the
      victim prior to the accident, any involved product, the location of the accident
      on the escalator, any medical treatment, what went wrong, opinion of the
      respondent on the causes of the accident, and personal characteristics of the
      passengers. Also, management must trade off productivity and safety appropriately
      to prevent "Organizational Accidents".

PMID- 16434014
TI  - Screening factors effecting a response in soluble protein expression: formalized
      approach using design of experiments.
AB  - We have integrated high-throughput expression and purification with quantitative
      protein analysis to identify factors influencing protein production. Application
      of high-throughput expression and purification, combined with automated gel
      capillary electrophoresis, allowed the quantitative analysis of multiple
      expression variables in a single experiment. An experimental design utilizing
      multiple factorial screens was employed to identify single factors and
      interactions having a significant impact on expression. As a test case,
      expression of the nonstructural protein NS3 from different hepatitis C virus
      genotypes (1b, 2a, and 3a) was examined in Escherichia coli. The 1b genotype of
      NS3 produced the highest level of expression, which was then further optimized
      using response surface modeling to give a four-fold increase in soluble protein
      levels. The quantitative and statistical approach presented has the capability of
      rapidly identifying interactions among experimental variables, leading to more
      reliable prediction of protein expression. We propose that this technique has
      universal application in the production of recombinant proteins, providing a
      powerful tool for the optimization of protein expression.

PMID- 16434015
TI  - A fluorescence-based assay for the reductase activity of protein disulfide
      isomerase.
AB  - We report on a new spectrofluorimetric assay for the measurement of reductase
      activity of proteins belonging to the superfamily of thioredoxins such as protein
      disulfide isomerase (PDI). The assay relies on the preparation of a fluorescence
      quenched substrate easily accessible in two steps through functional group
      transformations of the peptide Gly-Cys-Asp. In the first step fluorescein
      isothiocyanate is linked to the Gly-NH(2) terminus and in the second step the Cys
      SH groups are converted into a disulfide bond. Both intermediate and final
      substrate have been fully characterized by mass spectrometric and nuclear
      magnetic resonance measurements. Dimethyl sulfoxide is here reported to be a mild
      oxidizing agent allowing us to obtain in good overall yield the assay substrate
      in a single synthetic step. A reliable estimation of PDI reductase activity is
      obtained via the detection of a strong fluorescence enhancement after enzymatic
      reduction. Moreover, our assay provides further support for the key role played
      by thioredoxin reductase in enabling disulfide reductase activity of PDI.

PMID- 16434016
TI  - Amperometric bioelectrode for specific human immunoglobulin G determination:
      optimization of the method to diagnose American trypanosomiasis.
AB  - Bioelectrodes to detect immunoglobulin G (IgG) antibodies occurring in sera of
      patients suffering from American trypanosomiasis were assembled. The device
      consisted of a gold electrode modified with a thiol sensitized with parasite
      proteins. The assemblage was accomplished by adsorbing IgG antibodies from
      confirmed infected patients followed by adsorption of anti-human IgG labeled with
      a redox enzyme. The appliance was used as a working electrode in a three
      electrode cell containing a soluble charge-transfer mediator, also behaving as
      enzyme cosubstrate. The method is based on the measurement of the catalytic
      current after addition of the enzyme substrate, occurring when a positive serum
      is used to build up the biosensor. The discrimination efficiency between positive
      and negative sera was 100% for the samples studied. A 0.9525 correlation
      coefficient was obtained for results acquired by using this approach and one
      commercial diagnostic kit. The reproducibility, evaluated by the percentage
      coefficient of variation, varied between 7 and 20%. The sensitivity was 12.4 ng
      mL(-1) IgG, which is in the same order as that obtained with the commercial kit.
      Stability of the device was studied for a 7-day period and the results showed no
      significant change (p = 0.218). Leishmaniasic sera showed cross-reactivity when
      total parasite homogenate was used as antigen.

PMID- 16434017
TI  - HPLC with electrochemical detection to examine the pharmacokinetics of baicalin
      and baicalein in rat plasma after oral administration of a Kampo medicine.
AB  - A highly sensitive method for determining baicalin and baicalein in rat plasma
      was developed using micro HPLC with electrochemical detection (muHPLC-ED). Peak
      heights for baicalin and baicalein were found to be linearly related to the
      amounts injected, ranging from 2.2 pg to 4.5 ng (r = 0.997) and from 1.4 pg to
      2.7 ng (r = 0.997), respectively. The detection limits (signal/noise ratio = 3)
      of the current method for baicalin and baicalein were 0.89 and 0.54 pg,
      respectively. The concentrations of baicalin, baicalein, and their conjugates in
      rat plasma after oral administration of 2.0 mg/kg of Saiko-keishi-to (TJ-10) were
      determined. The glucuronide and sulfate forms of baicalin and baicalein in plasma
      were hydrolyzed enzymatically using beta-glucuronidase and sulfatase,
      respectively, and the hydrolyzed solutions were extracted with a 0.1-mol/L
      phosphoric acid-ethyl acetate mixture (1:1, v/v). Based on the time courses of
      the concentrations of the free and conjugated forms of baicalin and baicalein in
      rat plasma after oral administration of Saiko-keishi-to, the pharmacokinetic
      parameters of C(max), t(max), and AUC(0-6 h) were obtained.

PMID- 16434018
TI  - Analyses of dose-response curves to compare the antimicrobial activity of model
      cationic alpha-helical peptides highlights the necessity for a minimum of two
      activity parameters.
AB  - To assess and compare different model Leu-Lys-containing cationic alpha-helical
      peptides, their antimicrobial activities were tested against Escherichia coli as
      target organism over a broad peptide concentration range. The natural cationic
      alpha-helical peptides magainin 2 and PGLa and the cyclic cationic peptide
      gramicidin S were also tested between comparison. The dose-response curves
      differed widely for these peptides, making it difficult to rank them into an
      activity order over the whole concentration range. We therefore compared five
      different inhibition parameters from dose-response curves: IC(min) (lowest
      concentration leading to growth inhibition), IC(50) (concentration that gives 50%
      growth inhibition), IC(max) (related to minimum inhibition concentration and
      minimum bactericidal concentration), inhibition concentration factor (IC(F);
      describing the increase in concentration of the peptide between minimum and
      maximum inhibition), and activity slope (A(S); related to the Hill coefficient).
      We found that these parameters were covariant: two of them sufficed to
      characterize the dose dependence and hence the activity of the peptides. This was
      corroborated by showing that the dose dependences followed the Hill equation,
      with a small, constant aberration. We propose that the activity of antimicrobial
      peptides can readily be characterized by both IC(50) and IC(F) (or A(S)) rather
      than by a single parameter and discuss how this may relate to investigations into
      their mechanisms of action.

PMID- 16434019
TI  - Lab assembly of a low-cost, robust SYBR green buffer system for quantitative real
      time polymerase chain reaction.

PMID- 16434020
TI  - Differential scanning calorimetry as a tool to estimate binding parameters in
      multiligand binding proteins.
AB  - The stability of proteins and their interactions with other molecules is a topic
      of special interest in biochemistry because many cellular processes depend on
      that. New methods and approaches are constantly developed to elucidate the
      energetics of biomolecular recognition. In this sense, the application of the
      theory of macromolecular unfolding linked to ligand binding to differential
      scanning calorimetry (DSC) has proved to be a useful tool to simultaneously
      characterize the energetics of unfolding and binding. Although the general theory
      is well known, the applicability of DSC to study the interaction of biomolecules
      is not common. In the current work, we estimated the binding parameters of 8
      anilinonaphthalene-1-sulfonic acid to human serum albumin using DSC. This model
      system was chosen due to both the complex stoichiometry and the moderate binding
      constants. From DSC curves acquired at different ligand concentrations, we
      obtained the number of bound ligands, the binding constants, and the binding
      enthalpy for each independent binding site. Compared with those parameters
      determined by titration calorimetry, the results highlight the potentiality of
      DSC to estimate binding parameters in multiligand binding proteins.

PMID- 16434021
TI  - [Results of systematic subtotal parathyroidectomy with thymectomy for tertiary
      hyperparathyroidism after renal transplantation - 70 patients].
AB  - BACKGROUND: Due to the relatively small number of patients involved, there is
      currently no consensus on what operation should be performed in patients with
      tertiary hyperparathyroidism after renal transplantation. METHOD: Retrospective
      analysis of the 70 patients with tertiary hyperparathyroidism who all underwent
      subtotal parathyroidectomy with transcervical thymectomy in the same institution
      between 1978 and 2003. RESULTS: The delay between transplantation and
      parathyroidectomy was 4,1+/-4,3 years. Follow up was available for all patients.
      Mean follow-up was 5,6+/-5 years. Glomerular filtration rate (GFR) was 53+/-21
      ml/min at parathyroidectomy and 42+/-29 ml/min at follow-up [<30 ml/min in 26
      patients (37%), 30 - 60 ml/min in 25 patients (36%) et>60 ml/min in 19 patients
      (27%)]. One patient was successfully reoperated for persistent tertiary
      hyperparathyroidism during follow-up. No patient was hypercalcemic at follow-up.
      Four patients with a GFR<30 ml/min had a PTH level>fourfold normal values (6%)
      without signs or symptoms of hyperparathyroidism. One patient was hypocalcemic
      (1,5%) and two patients were normocalcemic with undetectable or infranormal PTH
      level (3%) under oral vitamin D and calcium medication. CONCLUSION: This approach
      permits not only to cure the majority of patients with tertiary
      hyperparathyroidism but also to avoid recurrence when the renal function
      declines. When medical management has failed, we recommend systematic subtotal
      parathyroidectomy with thymectomy for patients with tertiary hyperparathyroidism
      and this should usually be performed during the second year after
      transplantation.

PMID- 16434022
TI  - Modeled structure of the whole regulator G-protein signaling-2.
AB  - There is an increasing interest towards the mechanism by which regulators of G
      protein signaling regulate signals of G-protein-coupled receptors. RGS2 is a
      regulator of Gq protein signaling (RGS), the N-terminal region of which is known
      to contain determinants for G protein-coupled receptor recognition, but its
      structure is still unknown. To understand the molecular basis for this
      recognition, the three-dimensional model of RGS2, including N-terminal region and
      RGS box, was modeled. For this, RGS4 box structure and data from circular
      dichroism study of RGS2 N-terminal region were used. Then, membrane-targeting
      activity of the RGS2 amphipathic helix contained in the N-terminal region was
      investigated. Furthermore, in cellulo study provided first evidence that an
      internal sequence within the N-terminal region of RGS2 is involved in RGS2
      regulation of cholecystokinin receptor-2 signal. RGS2 modeled structure can now
      serve to study molecular recognition of RGS2 by signaling molecules.

PMID- 16434023
TI  - Aberrant expression of N-acetylglucosaminyltransferase-IVa and IVb (GnT-IVa and
      b) in pancreatic cancer.
AB  - The goal of this study was to identify glycosyltransferases that are specifically
      expressed in pancreatic cancer. To investigate the gene expression of
      glycosyltransferases between pancreatic cancer and normal pancreatic tissues, we
      performed DNA-microarray (involving about 1000 oligosaccharide-related genes)
      using RNA mixtures of pancreatic cancer cells and normal pancreatic tissues.
      Eighty-six genes were up-regulated and thirty-two were down-regulated in
      pancreatic cancer, compared to normal pancreatic tissue. Among these changes, it
      is noteworthy that the expression of GnT-IVa was decreased and the expression of
      GnT-IVb was increased in pancreatic cancer, compared to normal pancreatic
      tissues. Although GnT-IVa and -IVb are involved in the same reaction as a
      glycosyltransferase, their chromosomal localization is different. When 5 cases of
      pancreatic cancer tissues were examined using the real-time RT-PCR method, the
      expression of GnT-IVb was dominant in tumor tissues and the expression of GnT-IVa
      was dominant in the surrounding normal tissues. The expression of GnT-IVa was
      increased in all 3 cell lines that had been treated with 5-aza-C and butyrate.
      These results suggest that the down-regulation of GnT-IVa in pancreatic cancer
      cells is due to an epigenetic abnormality in the gene.

PMID- 16434024
TI  - Intermedin1-53 activates L-arginine/nitric oxide synthase/nitric oxide pathway in
      rat aortas.
AB  - Intermedin (IMD), a novel member of the calcitonin/calcitonin gene-related
      peptide (CGRP) family, has similar or more potent vasodilatory and hypotensive
      actions than adrenomedullin (ADM) and CGRP. The present study was designed to
      observe the effects of synthetic rat IMD1-53 on L-arginine (L-Arg) cellular
      transport, nitric oxide synthase (NOS) activity, and nitric oxide (NO) production
      in the isolated rat aortic ring to illustrate its direct effect on the L
      Arg/NOS/NO pathway in vasculature. IMD1-53 significantly increased NO production
      and cNOS activity in rat aortas and was more potent than equivalent ADM. But the
      peptides of both IMD and ADM had no effect on inducible NOS expression and
      activity. Otherwise, IMD1-53 induced a concentration-dependent increase in [3H]L
      Arg transport and its effect was more potent than that of an equivalent
      concentration of ADM. Semiquantitative RT-PCR revealed that IMD1-53 significantly
      increased cationic amino acid transport (CAT)-1 and CAT-2B mRNA expression, and
      its effect was similar to that of ADM. All these results suggest that IMD1-53
      might regulate vessel function homeostasis via upregulating the L-Arg/NOS/NO
      pathway.

PMID- 16434025
TI  - Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential.
AB  - Previously, we have demonstrated the long-term survival of myocardial cell sheet
      constructs in vivo, with microvascular network formation throughout the
      engineered tissues. The understanding and control of these vascularization
      processes are a key factor for creating thicker functional tissues. Here, we show
      that cardiac cell sheets express angiogenesis-related genes and form endothelial
      cell networks in culture. After non-invasive harvest and stacking of cell sheets
      using temperature-responsive culture dishes, these endothelial cell networks are
      maintained and result in neovascularization upon in vivo transplantation.
      Interestingly, we also discovered that all of the graft vessels are derived from
      the grafts themselves and these vessels migrate to connect with the host
      vasculature. Finally, blood vessel formation within the grafts can be controlled
      by changing the ratio of endothelial cells. In conclusion, myocardial tissue
      grafts engineered with cell sheet technology have their own inherent potential
      for the in vivo neovascularization that can be regulated in vitro.

PMID- 16434026
TI  - Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after
      vascular injury.
AB  - Lectin-like oxidized LDL receptor-1 (LOX-1) is an oxidized LDL receptor, and its
      role in restenosis after angioplasty remains unknown. We used a balloon-injury
      model of rabbit aorta, and reverse transcription-polymerase chain reaction
      revealed that LOX-1 mRNA expression was modest in the non-injured aorta, reached
      a peak level 2 days after injury, and remained elevated until 24 weeks after
      injury. Immunohistochemistry and in situ hybridization showed that LOX-1 was not
      detected in the media of non-injured aorta but expressed in both medial and
      neointimal smooth muscle cells (SMC) at 2 and 24 weeks after injury. Low
      concentrations of ox-LDL (10 microg/mL) stimulated the cultured SMC
      proliferation, which was inhibited by antisense oligonucleotides of LOX-1 mRNA.
      Double immunofluorescence staining showed the colocalization of LOX-1 and
      proliferating cell nuclear antigen in human restenotic lesion. These results
      suggest that LOX-1 mediates ox-LDL-induced SMC proliferation and plays a role in
      neointimal formation after vascular injury.

PMID- 16434027
TI  - Structural characterization of the papaya cysteine proteinases at low pH.
AB  - Current control of gastrointestinal nematodes relies primarily on the use of
      synthetic drugs and encounters serious problems of resistance. Oral
      administration of plant cysteine proteinases, known to be capable of damaging
      nematode cuticles, has recently been recommended to overcome these problems. This
      prompted us to examine if plant cysteine proteinases like the four papaya
      proteinases papain, caricain, chymopapain, and glycine endopeptidase that have
      been investigated here can survive acidic pH conditions and pepsin degradation.
      The four papaya proteinases have been found to undergo, at low pH, a
      conformational transition that instantaneously converts their native forms into
      molten globules that are quite unstable and rapidly degraded by pepsin. As shown
      by activity measurements, the denatured state of these proteinases which finally
      results from acid treatment is completely irreversible. It is concluded that
      cysteine proteinases from plant origin may require to be protected against both
      acid denaturation and proteolysis to be effective in the gut after oral
      administration.

PMID- 16434029
TI  - Induction of CITED2 expression in the rat hippocampus following transient global
      ischemia.
AB  - CITED2 is implicated in the modulating the activity of HIF-1 which is a major
      transcription factor involved in ischemia-related gene expression. Following
      transient forebrain ischemia, we found that CITED2 was induced in a subset of
      brain regions including dentate gyrus of the hippocampal formation and piriform
      cortex. Because CITED2 was not induced in cultured neurons exposed to oxygen
      glucose deprivation, we concluded that hypoxia is not sufficient to trigger its
      induction.

PMID- 16434028
TI  - Differential activity of kaempferol and quercetin in attenuating tumor necrosis
      factor receptor family signaling in bone cells.
AB  - Increasing data from epidemiological and in vitro studies show that the
      isoflavonoids, genistein and daidzein, and the flavonols, quercetin and
      kaempferol, are protective against postmenopausal bone loss. However, the
      physiological mechanisms for these effects are not well understood. We now report
      that kaempferol exerts profound antiosteoclastogenic effects by acting on both
      osteoblasts and osteoclasts. Kaempferol but not quercetin dose-dependently
      inhibited tumor necrosis factor alpha (TNFalpha)-induced production of the
      osteoclastogenic cytokines interleukin-6 (IL-6) and monocyte chemoattractant
      protein-1 (MCP-1/CCL2) in osteoblasts. The effect on IL-6 was
      posttranscriptional, whereas kaempferol reduced MCP-1 mRNA levels. In addition,
      in mouse primary calvarial osteoblasts, kaempferol but not quercetin blocked
      TNFalpha-induced translocation of the nuclear factor kappaB (NF-kappaB) subunit
      p65 from the cytoplasm to the nucleus. However, TNFalpha-stimulated intracellular
      ROS production was unaltered by kaempferol. In RAW264.7 cells, a
      monocyte/macrophage precursor for osteoclasts, both kaempferol and quercetin dose
      dependently inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced
      immediate-early oncogene c-fos expression at 6 h. After 3-5 days, both flavonols
      robustly inhibited RANKL-induced expression of the osteoclastic differentiation
      markers, RANK and calcitonin receptor. Consistent with down regulation of these
      osteoclastic differentiation markers, both flavonols strongly attenuated the
      RANKL-induced formation of multinucleated osteoclasts. However, kaempferol was
      more potent than quercetin in inhibiting RANKL-stimulated effects on RAW264.7
      cells. Thus, our data indicate that kaempferol exerts profound
      antiosteoclastogenic effects by specifically antagonizing TNF receptor family
      action on bone cells at two distinct levels, by disrupting production of
      osteoclastogenic cytokines from osteoblasts and attenuating osteoclast precursor
      cell differentiation.

PMID- 16434030
TI  - Modulatory role of lipoic acid on adriamycin-induced testicular injury.
AB  - The present study investigated the protective efficacy of dl-alpha-lipoic acid
      (LA) on adriamycin (ADR)-induced oxidative damage in rat testis. Adult male
      albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.),
      once a week for 10 weeks. ADR injected rats showed increased oxidative stress
      with a concomitant decrease in cellular thiols. The mRNA level for phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) was also significantly decreased by
      ADR administration. Transmission electron microscopic (TEM) observations of
      testicular germ cells revealed abnormal ultrastructural changes in ADR treated
      rats. Treatment with lipoic acid (35 mg/kg body weight, i.p.) 1 day prior to ADR
      administration, effectively reverted these abnormal changes towards normalcy.
      These findings indicate a cytoprotective role of LA in this experimental model of
      testicular toxicity.

PMID- 16434031
TI  - The integration of figurative language and static depictions: an eye movement
      study of fictive motion.
AB  - Do we view the world differently if it is described to us in figurative rather
      than literal terms? An answer to this question would reveal something about both
      the conceptual representation of figurative language and the scope of top-down
      influences on scene perception. Previous work has shown that participants will
      look longer at a path region of a picture when it is described with a type of
      figurative language called fictive motion (The road goes through the desert)
      rather than without (The road is in the desert). The current experiment provided
      evidence that such fictive motion descriptions affect eye movements by evoking
      mental representations of motion. If participants heard contextual information
      that would hinder actual motion, it influenced how they viewed a picture when it
      was described with fictive motion. Inspection times and eye movements scanning
      along the path increased during fictive motion descriptions when the terrain was
      first described as difficult (The desert is hilly) as compared to easy (The
      desert is flat); there were no such effects for descriptions without fictive
      motion. It is argued that fictive motion evokes a mental simulation of motion
      that is immediately integrated with visual processing, and hence figurative
      language can have a distinct effect on perception.

PMID- 16434032
TI  - Sphingosine-1-phosphate inhibits cell migration and endothelial to mesenchymal
      cell transformation during cardiac development.
AB  - Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid metabolite
      that exerts important effects on numerous cellular events via cell surface
      receptors, S1P(1-5). S1P influences differentiation, proliferation, and migration
      during vascular development. However, the effects of S1P signaling on early
      cardiac development are not well understood. To address this issue, we examined
      the expression of S1P regulatory enzymes and S1P receptors during cardiac
      development. We observed that enzymes that regulate S1P levels, sphingosine
      kinase and sphingosine-1-phosphate phosphatase, are expressed in the developing
      heart. In addition, RT-PCR revealed that four of the five known S1P receptors
      (S1P(1-4)) are also expressed in the developing heart. Next, effects of altered
      S1P levels on whole embryo and atrioventricular (AV) canal cultures were
      investigated. We demonstrate that inactivation of the S1P producing enzyme,
      sphingosine kinase, leads to cell death in cardiac tissue which is rescued by
      exogenous S1P treatment. Other experiments reveal that increased S1P
      concentration prevents alterations in cell morphology that are required for cell
      migration. This effect results in reduced cell migration and inhibited
      mesenchymal cell formation in AV canal cushion tissue. These data indicate that
      S1P, locally maintained within a specific concentration range, is an important
      and necessary component of early heart development.

PMID- 16434033
TI  - Nanomedicine for respiratory diseases.
AB  - Nanotechnology provides new materials in the nanometer range with many potential
      applications in clinical medicine and research. Due to their unique size
      dependent properties nanomaterial such as nanoparticles offer the possibility to
      develop both new therapeutic and diagnostic tools. Thus, applied nanotechnology
      to medical problems--nanomedicine--can offer new concepts that are reviewed. The
      ability to incorporate drugs into nanosystems displays a new paradigm in
      pharmacotherapy that could be used for cell-targeted drug delivery. Nontargeted
      nanosystems such as nanocarriers that are coated with polymers or albumin and
      solid lipid particles have been used as transporter in vivo. However, nowadays
      drugs can be coupled to nanocarriers that are specific for cells and/or organs.
      Thus, drugs that are either trapped within the carriers or deposited in
      subsurface oil layers could be specifically delivered to organs, tumors and
      cells. These strategies can be used to concentrate drugs in selected target
      tissues thus minimizing systemic side effects and toxicity. In addition to these
      therapeutic options, nanoparticle-based "molecular" imaging displays a field in
      which this new technology has set the stage for an evolutionary leap in
      diagnostic imaging. Based on the recent progress in nanobiotechnology there is
      potential for nanoparticles and -systems to become useful tools as therapeutic
      and diagnostic tools in the near future.

PMID- 16434034
TI  - Evidence for a differential functional regulation of the two beta(3)-integrins
      alpha(V)beta(3) and alpha(IIb)beta(3).
AB  - The functional regulation of integrins is a major determinant of cell adhesion,
      migration and tissue maintenance. The binding of cytoskeletal proteins to various
      sites of integrin cytoplasmic domains is a key mechanism of this functional
      regulation. Expression of recombinant integrin alpha(IIb)beta(3) and
      alpha(M)beta(2) lacking the GFFKR-region in CHO cells results in constitutively
      activated integrins. In contrast, CHO cells stably expressing either a GFFKR
      deleted alpha(V(del))beta(3) or a FF to AA-substituted alpha(V(AA))beta(3) do not
      reveal a constitutively activated integrin. Adhesion to immobilized fibrinogen is
      strongly impaired in alpha(V(del))beta(3) or alpha(V(AA))beta(3)-expressing
      cells, whereas it is not impaired in alpha(IIb)beta(3) and alpha(M)beta(2), both
      lacking the GFFKR-region. In a parallel plate flow chamber assay, alpha(V)beta(3)
      expressing cells adhere firmly to fibrinogen and spread even at shear rates of 15
      to 20 dyn/cm(2), whereas alpha(V(del))beta(3) or alpha(V(AA))beta(3) cells are
      detached at 15 dyn/cm(2). Actin stress fiber formation and focal adhesion plaques
      containing alpha(V)beta(3) are observed in alpha(V)beta(3) cells but not in
      alpha(V(del))beta(3) or alpha(V(AA))beta(3)-expressing cells. As an additional
      manifestation of impaired outside-in signaling, phosphorylation of pp125(FAK) was
      reduced in these cells. In summary, we report that the GFFKR-region of the
      alpha(V)-cytoplasmic domain and in particular two phenylalanines are essential
      for integrin alpha(V)beta(3) function, especially for outside-in signaling. Our
      results suggest that the two beta(3)-integrins alpha(IIb)beta(3) and
      alpha(V)beta(3) are differentially regulated via their GFFKR-region.

PMID- 16434035
TI  - Cortactin regulates podosome formation: roles of the protein interaction domains.
AB  - Cortactin, a multi-domain scaffolding protein involved in actin polymerization,
      is enriched in podosomes induced by phorbol ester in vascular smooth muscle
      cells. We generated several functional and truncation mutants of cortactin to
      probe the roles of various protein interaction domains in the regulation of the
      dynamics of podosome formation. At the onset of podosome genesis, cortactin
      clustered near the ends of stress fibers that appeared to act as nucleation
      platforms onto which the actin polymerization machinery assembled. Translocation
      of cortactin to these pre-podosome clusters required the intact N-WASp-binding
      SH3 domain. Overexpression of the C-terminal third of cortactin containing the
      intact SH3 domain inhibited podosome formation presumably by sequestering of N
      WASp and prevented cortactin clustering. Subsequent assembly of the actin-rich
      core of podosomes required translocation of additional cortactin to the actin
      core, a process that required the actin-binding repeats, but not the Arp2/3
      binding N-terminal acidic region nor the SH3 domain. These results suggest that
      the SH3 domain and the actin-binding repeat region are involved, respectively, in
      the early and late stages of podosome formation process.

PMID- 16434036
TI  - Chemokine-directed migration of tumor-inhibitory neural progenitor cells towards
      an intracranially growing glioma.
AB  - We have earlier shown that the rat neural progenitor cell line HiB5 is capable of
      suppressing intracranial growth of glioma cells in Fisher rats. Unlike some
      neural progenitor cells, HiB5 cells have not shown homing capacity towards glioma
      cells growing intracranially. In this study, we have genetically modified HiB5
      progenitor cells to over-express the chemokine receptor CXCR3. We show that the
      introduced receptor is functionally responding to ligand stimulation with
      increased phosphorylation levels of ERK and SAPK/JNK and a transcriptional
      response of an AP-1 reporter system introduced into HIB5 cells. These transfected
      progenitor cells migrate in vitro in response to IP-10 and I-TAC. Further, we
      show an enhanced in vivo migration of the CXCR3 transfected HiB5 cells over the
      corpus callosum towards an IP-10 and I-TAC expressing glioma, as compared to wild
      type HiB5 cells. Our data indicate that it is possible to take advantage of
      chemokines natural capacity to initiate migratory responses, and to use this
      ability to enhance tumor-inhibitory neural progenitor cells to target an
      intracranially growing glioma.

PMID- 16434039
TI  - Length of laparotomy incision and surgical stress assessed by serum IL-6 level.
AB  - BACKGROUND: Because surgical stress is thought to have an effect on morbidity,
      mortality, and remnant tumour progression after surgery, diminishing surgical
      stress is important. The purpose of this study was to assess in a murine model
      whether the length and type of laparotomy incision influence surgical stress.
      METHODS: Serum IL-6 concentrations were measured sequentionally in 220 male
      BALB/c mice who were assigned to different basic laparotomies, (1-cm versus 2-cm
      versus 3-cm laparotomy with or without caecal resection), other types of
      laparotomy (3-cm, 1-cm x 3, 3-cm transverse, 3-cm laparotomy with rapid closure),
      or 3-cm skin incision with or without laparotomy. The serum level of IL-6 was
      measured by ELISA. RESULTS: Serum IL-6 levels at 3 and 6h after surgery were
      significantly higher in the 3-cm laparotomy group (1,680+/-802pg/ml and 1,066+/
      507pg/ml, respectively), than in the 1-cm laparotomy group (797+/-427pg/ml and
      515+/-212pg/ml, respectively). When caecal resection was added, the serum IL-6
      level at 6h was significantly higher in the 3-cm laparotomy group (2,844+/
      134pg/ml) than in the 1-cm laparotomy group (2,200+/-379pg/ml). Although the type
      of laparotomy incision was not associated with the serum level of IL-6, the serum
      IL-6 level after midline skin incision without laparotomy (245+/-142pg/ml) was
      significantly lower than that after 3-cm laparotomy (1,680+/-802pg/ml).
      CONCLUSIONS: The length of laparotomy incision was correlated with the serum
      level of IL-6 in a murine model. The surgical stress related to abdominal
      procedures might be decreased when laparotomy wounds are kept as small as
      possible.

PMID- 16434038
TI  - Effect of activin A and inhibin A on expression of the inhibin/activin beta-B
      subunit and gonadotropin receptors in granulosa cells of the hen.
AB  - Activin A has been shown to be abundant in the theca layer of the large pre
      ovulatory follicles of the hen whereas inhibin A is produced in the granulosa
      layer. The purpose of this study was to investigate the effects of activin A and
      inhibin A on granulosa cell expression of inhibin beta-B-subunit, FSH receptor
      (FSHR), and LH receptor (LHR). Granulosa cells were isolated from the F1, F3+F4,
      and small yellow follicles (SYF; 6-12 mm diameter) of laying hens and pooled
      according to size. The cells were dispersed and plated in the presence of 0, 10,
      or 50 ng/ml recombinant human activin A (n=5 replicate cultures). RNA was
      subsequently extracted from the cells and Northern blots performed. Cell
      proliferation was determined for all treatments. An identical set of experiments
      was performed in which the granulosa cells were treated with recombinant human
      inhibin A (n=4 replicate cultures). Treatment with activin A at 50 ng/ml
      significantly (p<0.05) increased expression of beta-B-subunit for granulosa cells
      from all follicles. This dose also significantly increased expression of FSHR in
      granulosa cells from all follicles (p<0.05) and increased expression of LHR in
      cells from F1 and F3+F4 follicles (p<0.01) with no significant effect on cells
      from the SYF. Overall, activin A treatment significantly (p<0.05) decreased cell
      proliferation at the 50 ng/ml dose. Inhibin A had no significant effect on
      expression of beta-B-subunit, FSHR or LHR at any dose. There was a moderate
      stimulatory effect of inhibin A on granulosa cell proliferation. These results
      suggest that activin A may have an important role in regulating granulosa cell
      responsiveness to gonadotropins while also modulating follicle development by
      attenuating cell proliferation.

PMID- 16434037
TI  - Forced expression of the motor neuron determinant HB9 in neural stem cells
      affects neurogenesis.
AB  - In contrast to mouse embryonic stem cells and in spite of overlapping gene
      expression profiles, neural stem cells (NSCs) isolated from the embryonic spinal
      cord do not respond to physiological morphogenetic stimuli provided by Sonic
      hedgehog and retinoic acid and do not generate motor neurons upon
      differentiation. Transcription factors expressed in motor neuron progenitors
      during embryogenesis include Pax6, Ngn2, Nkx6.1 and Olig2, whose expression
      precedes that of factors specifying motor neuron fate, including HB9, Islet1 and
      LIM3. We showed that all these factors were present in neural progenitors derived
      from mouse ES cells, whereas NSCs derived from the rat embryonic spinal cord
      expressed neither HB9 nor Islet1 and contained low levels of Nkx6.1 and LIM3. We
      constructed a lentivirus vector to express HB9 and GFP in NSCs and examined the
      consequences of HB9 expression on other transcription factors and cell
      differentiation. Compared to cell expressing GFP alone, NSCs expressing GFP and
      HB9 cycled less rapidly, downregulated Pax6 and Ngn2 mRNA levels, produced higher
      proportions of neurons in vitro and lower numbers of neurons after
      transplantation in the spinal cord of recipient rats. Oligodendrocytic and
      astrocytic differentiations were not affected. HB9 expressing NSCs did not
      express Islet1 or upregulate LIM3. They neither responded to Sonic hedgehog and
      retinoic acid nor produced cholinergic neurons. We concluded that forced HB9
      expression affected neurogenesis but was not sufficient to confer motor neuron
      fate to NSCs.

PMID- 16434040
TI  - Endoscopic laser surgery after therapeutic amniocentesis in the treatment of
      severe twin--twin transfusion syndrome.

PMID- 16434041
TI  - Prenatal, labor and delivery characteristics of mothers with macrosomic babies.

PMID- 16434042
TI  - Vulvovaginal candidiasis.

PMID- 16434043
TI  - Impact of early admission in labor on method of delivery.
AB  - OBJECTIVE: The effect of the timing of admission in labor unit on the method of
      delivery was evaluated in a cohort study. METHOD: Four hundred and sixty six low
      risk nulliparous women who were admitted in the labor unit in latent phase (group
      1) were compared with 329 parturient women who were admitted in the active phase
      (group 2) to determine rate of and reasons for cesarean section, cervical
      dilation at the time of cesarean, and the rate of labor augmentation. RESULT: The
      number of cesarean deliveries in group 1 was greater than that in the group 2
      (301 vs 80, p<0.0001 ). The main reason for cesarean section in group 1 was
      dystocia, and in 2, fetal distress. The rate of cesarean section in the women who
      were augmented was greater in group 1 than in group 2 (54% vs 23%, p<0.0001).
      CONCLUSION: Later admission in labor increases the rate of spontaneous vaginal
      delivery in low risk nulliparous women.

PMID- 16434044
TI  - Abnormal release of nitric oxide from nitrosoprotein in preeclampsia.

PMID- 16434045
TI  - Assessment of fetal pulmonary artery flow by Doppler echocardiography after
      antenatal corticoid therapy.

PMID- 16434046
TI  - Amniotic fluid endothelin levels and the incidence of premature rupture of
      membranes.
AB  - Objective. The purpose of this prospective study was to record Endothelin 1 (ET1)
      concentrations in the second trimester amniotic fluid and in women who develop
      premature rupture of membranes (PROM), preterm premature rupture of the membranes
      (PPROM) and in women with uneventful pregnancies. Method. Amniotic fluid was
      retrieved by amniocentesis from 125 women in the second trimester of pregnancy.
      The levels of Endothelin were measured by a sensitive and specific
      radioimmunoassay. Results. From the 125 women included in the study 20 developed
      PROM and preterm PROM (13 PPROM and 7 PROM). The ET1 concentration was
      significantly higher (P<0.001) in PROM and PPROM than in normal pregnancy (96.4
      vs. 43 pg/ml). The sub-analysis of the two rupture of membranes groups found that
      the concentration of ET1 was higher in the PPROM than in PROM (118 vs. 72 pg/ml).
      Conclusion. The amniotic fluid concentration of ET1 is elevated by the second
      trimester in women who later develop preterm PROM or term PROM.

PMID- 16434047
TI  - Adventitial VEGF165 gene transfer prevents lumen loss through induction of
      positive arterial remodeling after PTCA in porcine coronary arteries.
AB  - Negative arterial remodeling still plays an important role in the pathogenesis of
      coronary restenosis even in the era of interventional stenting (e.g. arterial
      narrowing occurs proximal and distal of a stented segment). Previous studies
      suggest that increased angiogenesis and inhibited regression of injury-induced
      adventitial microvessels prevents negative remodeling. We have examined the
      effect of local vascular endothelial growth factor (VEGF(165)) gene transfer on
      adventitial microvessel angiogenesis/regression and arterial remodeling after
      coronary angioplasty. Twenty pigs underwent angioplasty, each one in two major
      coronary arteries, followed by plasmid liposome gene transfer with either
      VEGF(165) or control gene LacZ (50 microg DNA with 50 microg of Lipofectine) into
      the (peri)adventitial space using a needle injection catheter. Arteries were
      examined at days 1, 7, 14, and 28. Local delivery of VEGF(165) gene into the
      outer compartments of balloon-injured porcine coronary arteries reduced lumen
      area loss due to distinct positive remodeling (arterial enlargement). Prevention
      of adventitial microvessel regression, enhanced adventitial elastin accumulation,
      reduced adventitial myofibroblast numbers, and a pronounced adventitial
      inflammatory response considered as a part of arterial healing seem to be the
      main VEGF-mediated mechanisms indicating the therapeutic potential of VEGF for
      restenosis prevention.

PMID- 16434048
TI  - Tensile behavior of cortical bone: dependence of organic matrix material
      properties on bone mineral content.
AB  - A porous composite model is developed to analyze the tensile mechanical
      properties of cortical bone. The effects of microporosity (volksman's canals,
      osteocyte lacunae) on the mechanical properties of bone tissue are taken into
      account. A simple shear lag theory, wherein tensile loads are transferred between
      overlapped mineral platelets by shearing of the organic matrix, is used to model
      the reinforcement provided by mineral platelets. It is assumed that the organic
      matrix is elastic in tension and elastic-perfectly plastic in shear until it
      fails. When organic matrix shear stresses at the ends of mineral platelets reach
      their yield values, the stress-strain curve of bone tissue starts to deviate from
      linear behavior. This is referred as the microscopic yield point. At the point
      where the stress-strain behavior of bone shows a sharp curvature, the organic
      phase reaches its shear yield stress value over the entire platelet. This is
      referred as the macroscopic yield point. It is assumed that after macroscopic
      yield, mineral platelets cannot contribute to the load bearing capacity of bone
      and that the mechanical behavior of cortical bone tissue is determined by the
      organic phase only. Bone fails when the principal stress of the organic matrix is
      reached. By assuming that mechanical properties of the organic matrix are
      dependent on bone mineral content below the macroscopic yield point, the model is
      used to predict the entire tensile mechanical behavior of cortical bone for
      different mineral contents. It is found that decreased shear yield stresses and
      organic matrix elastic moduli are required to explain the mechanical behavior of
      bones with lowered mineral contents. Under these conditions, the predicted values
      (elastic modulus, 0.002 yield stress and strain, and ultimate stress and strain)
      are within 15% of experimental data.

PMID- 16434049
TI  - The challenge of cross-cultural assessment--The Test of Ability To Explain for
      Zulu-speaking Children.
AB  - A culturally appropriate test, The Test of Ability To Explain for Zulu-speaking
      Children (TATE-ZC), was developed to measure verbal problem solving skills of
      rural, Zulu-speaking, primary school children. Principles of 'non-biased'
      assessment, as well as emic (culture specific) and etic (universal) aspects of
      intelligence formed the theoretical backdrop. In addition, specific principles
      relating to test translation; test content; culturally appropriate stimulus
      material; scoring procedures and test administration were applied. Five
      categories of abstract thinking skills formed the basis of the TATE-ZC. These
      were: (a) Explaining Inferences, (b) Determining Cause, (c) Negative Why
      Questions, (d) Determining Solutions and (e) Avoiding Problem. The process of
      test development underwent three pilot studies. Results indicate that the TATE-ZC
      is a reliable and valid test for the target population. A critical analysis of
      the efficacy of creating a test of verbal reasoning for children from the
      developing world concludes the article. LEARNING OUTCOMES: As a result of this
      activity (1) the participant will have a clearer understanding of the principles
      that need to be followed when developing culturally appropriate test material;
      (2) the participant will understand the process of developing culturally
      appropriate test material for non-mainstream cultures; (3) the participant will
      be able to apply the process and principles to other cross-cultural testing
      situations.

PMID- 16434050
TI  - Identity elements required for enzymatic formation of N2,N2-dimethylguanosine
      from N2-monomethylated derivative and its possible role in avoiding alternative
      conformations in archaeal tRNA.
AB  - Here, we have investigated the specificity of purified recombinant
      tRNA:m(2)(2)G10 methyltransferase of Pyrococcus abyssi ((Pab)Trm-m(2)(2)G10
      enzyme). This archaeal enzyme catalyses mono- and dimethylation of the N(2)
      exocyclic amino group of guanine at position 10 of several tRNA species. Our
      results indicate that only few identity elements are required for the efficient
      formation of m(2)(2)G10. They are composed of a G10.U25 wobble base-pair in the
      dihydrouridine arm (D-arm) and a four nucleotide variable loop (V-loop) within a
      canonical three-dimensional (3D) structure. The types of base-pairs in the D-arm
      or amino acid acceptor stem are also important for the enzymatic reaction, but
      appear to affect only the rate of tRNA methylation. However, in tRNA species
      harbouring a G10-C25 Watson-Crick base-pair and/or five nucleotide V-loop, only
      m(2)G10 is produced. To impair the monomethylation reaction, drastic amputation
      in the T-arm is required. Our observations contrast with those reported earlier
      for the identity elements required for a remotely related Pyrococcus furiosus Trm
      m(2)(2)G26 enzyme (alias (Pfu)Trm1) that also catalyses the two step formation of
      m(2)(2)G but at position 26 in several tRNA species. In this case, a G10-C25 base
      pair together with the five nucleotide V-loop were shown to be required for
      efficient formation of m(2)(2)G26. Thus, in the Pyrococcus genus, the major
      identity elements that preclude formation of m(2)(2)G at positions 10 or 26 in
      tRNA are mutually exclusive. Therefore, the Trm-m(2)(2)G10 and Trm-m(2)(2)G26
      enzymes have evolved independently towards different specificities. In addition,
      identity elements for m(2)/m(2)(2)G10 formation in archaeal tRNA are different
      from the ones required for m(2)G10 formation in eukaryal tRNA. We propose that
      archaeal tRNA:m(2)(2)G10 methyltransferases, unlike the orthologous eukaryal
      tRNA:m(2)G10 methyltransferases, evolved towards m(2)(2)G10 specificity due to
      the possible requirement of preventing formation of alternative structures in G/C
      rich archaeal tRNA species.

PMID- 16434051
TI  - Spatial assembly and RNA binding stoichiometry of a LINE-1 protein essential for
      retrotransposition.
AB  - LINE-1, or L1, is a highly successful retrotransposon in mammals, comprising 17%
      and 19% of the human and mouse genomes, respectively. L1 retrotransposition and
      hence amplification requires the protein products of its two open reading frames,
      ORF1 and ORF2. The sequence of the ORF1 protein (ORF1p) is not related to any
      protein with known function. ORF1p has RNA binding and nucleic acid chaperone
      activities that are both required for retrotransposition. Earlier studies have
      shown that ORF1p forms a homotrimer with an asymmetric dumbbell shape, in which a
      rod separates a large end from a small end. Here, we determine the topological
      arrangement of monomers within the homotrimer by comparing atomic force
      microscopy (AFM) images of the full ORF1p with those of truncations containing
      just the N or C-terminal regions. In addition, AFM images of ORF1p bound to RNA
      at high protein/RNA molar ratios show that ORF1p can form tightly packed clusters
      on RNA, with binding occurring at the C-terminal domain. The number of bound
      ORF1p trimers increases with increasing length of the RNA, revealing that the
      binding site size is about 50 nt, a value confirmed by nitrocellulose filter
      binding under stoichiometric conditions. These results are consistent with a role
      for ORF1p during L1 retrotransposition that includes both coating the RNA and
      acting as a nucleic acid chaperone. Furthermore, these in vitro L1
      ribonucleoprotein particles provide insight into the structure of the L1
      retrotransposition intermediate.

PMID- 16434052
TI  - Bacteriorhodopsin folds into the membrane against an external force.
AB  - Despite their crucial importance for cellular function, little is known about the
      folding mechanisms of membrane proteins. Recently details of the folding energy
      landscape were elucidated by atomic force microscope (AFM)-based single molecule
      force spectroscopy. Upon unfolding and extraction of individual membrane proteins
      energy barriers in structural elements such as loops and helices were mapped and
      quantified with the precision of a few amino acids. Here we report on the next
      logical step: controlled refolding of single proteins into the membrane. First
      individual bacteriorhodopsin monomers were partially unfolded and extracted from
      the purple membrane by pulling at the C-terminal end with an AFM tip. Then by
      gradually lowering the tip, the protein was allowed to refold into the membrane
      while the folding force was recorded. We discovered that upon refolding certain
      helices are pulled into the membrane against a sizable external force of several
      tens of picoNewton. From the mechanical work, which the helix performs on the AFM
      cantilever, we derive an upper limit for the Gibbs free folding energy.
      Subsequent unfolding allowed us to analyze the pattern of unfolding barriers and
      corroborate that the protein had refolded into the native state.

PMID- 16434053
TI  - Crystal structures of Yersinia enterocolitica salicylate synthase and its complex
      with the reaction products salicylate and pyruvate.
AB  - The salicylate synthase, Irp9, from Yersinia enterocolitica is involved in the
      biosynthesis of the siderophore yersiniabactin. It is a bifunctional enzyme that
      forms salicylate and pyruvate from chorismate and water via the intermediate
      isochorismate. Here we report the first crystal structure of Irp9 and also of its
      complex with the reaction products salicylate and pyruvate at 1.85 A and 2.1 A
      resolution, respectively. Like other members of the chorismate-utilizing enzyme
      family, e.g. the TrpE subunit of anthranilate synthase and the PabB subunit of 4
      amino-4-deoxychorismate synthase, Irp9 has a complex alpha/beta fold. The crystal
      structure of Irp9 contains one molecule each of phosphate and acetate derived
      from the crystallization buffer. The Irp9-products complex structure was obtained
      by soaking chorismate into Irp9, demonstrating that the enzyme is still
      catalytically active in the crystal. Both structures contain Mg(2+) in the active
      site. There is no evidence of the allosteric tryptophan binding site found in
      TrpE and PabB. Mutagenesis of Glu240, His321 and Tyr372 provided some insight
      into the mechanism of the two transformations catalyzed by Irp9. Knowledge of the
      structure of Irp9 will guide the search for potent inhibitors of salicylate
      formation, and hence of bacterial iron uptake, which is directly related to the
      virulence of Yersinia.

PMID- 16434054
TI  - Crystal structure of RAIDD death domain implicates potential mechanism of
      PIDDosome assembly.
AB  - Caspase-2 is implicated in stress-induced apoptosis that acts as an upstream
      initiator of mitochondrial permeabilization. Recent studies have shown that
      caspase-2 activation requires a molecular complex known as the PIDDosome
      comprising the p53-inducible protein PIDD, the adapter protein RAIDD and caspase
      2. RAIDD has an N-terminal caspase recruitment domain (CARD) that interacts with
      the CARD of caspase-2 and a C-terminal death domain (DD) that interacts with the
      DD in PIDD. As a first step towards elucidating the molecular mechanisms of
      caspase-2 activation, we report the crystal structure of RAIDD DD at 2.0 A
      resolution. The high-resolution structure reveals important features of RAIDD DD
      that may be important for DD folding and dynamics and for assembly of the
      PIDDosome.

PMID- 16434055
TI  - Decreased T cellular immune response in schizophrenic patients.
AB  - The involvement of an alteration of the immune system in the pathogenesis of
      schizophrenia is discussed since many years. In particular, in vitro studies give
      evidence that the T helper-1 (Th1) mediated cellular immune response is deficient
      in schizophrenia. We therefore hypothesized that the type-IV delayed skin
      hypersensitivity reaction, which is effected by the Th1 immune response, is
      attenuated in schizophrenia patients. A prospective case-control study was
      performed to assess skin reactivity of 30 patients vs. 30 age and sex matched
      healthy controls. A standardized device with seven different antigens (Multitest
      Immignost) was applied intracutaneously; after 48h, the skin reactions were
      quantified. In general, the mean skin reaction of the schizophrenic patients were
      significantly smaller as compared to the healthy control group. Moreover,
      significantly more schizophrenic patients showed a diminished skin reaction to
      distinct antigens. Our findings demonstrate a markedly attenuated in vivo type-1
      mediated cellular immune response in schizophrenic patients, further confirming
      the hypothesis of a relative Th2 shift in schizophrenia.

PMID- 16434056
TI  - Cerebrospinal fluid kynurenic acid in male and female controls - correlation with
      monoamine metabolites and influences of confounding factors.
AB  - The concentrations of the tryptophan metabolite kynurenic acid (KYNA) and the
      monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5
      HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in the
      cerebrospinal fluid (CSF) from 43 healthy volunteers (30 males and 13 females).
      Healthy female controls displayed higher CSF concentration of KYNA (1.91nM+/
      0.20) compared to healthy male controls (1.06nM+/-0.07) and lower CSF levels of
      HMPG (39.2nM+/-2.0 and 43.4+/-1.2, respectively). CSF levels of HVA and 5-HIAA
      did not differ between females (181.3nM+/-21.9 and 93.7nM+/-11.4, respectively)
      and males (138.9nM+/-12.6 and 74.8nM+/-5.9, respectively). Positive
      intercorrelations were found between CSF KYNA, HVA and 5-HIAA while CSF content
      of HMPG did not correlate with KYNA or the other monoamine metabolites in CSF. A
      negative correlation was found between back length and CSF concentrations of
      KYNA, HVA and 5-HIAA and also between CSF KYNA levels and body height. The
      results of the present study suggest that concentrations of KYNA and the
      monoamine metabolites in CSF from healthy controls are dependent on gender and
      back length, which must be taken in consideration when analysing mixed groups of
      men and women. The higher KYNA concentration found in female controls compared to
      male might be attributed to a shorter back in women compared to men. Furthermore,
      these findings suggest that increased KYNA formation is associated with an
      increased dopamine and serotonin turnover.

PMID- 16434057
TI  - Fatigue in multiple sclerosis is related to disability, depression and quality of
      life.
AB  - Fatigue in multiple sclerosis is a frequent and disabling symptom that can
      interfere in daily functioning. The aim of this study is to demonstrate the
      relationship between fatigue and disability, disease course, depression and
      quality of life. We administered French valid versions of the Fatigue Impact
      Scale (EMIF-SEP), the short form of the Beck depression inventory (13 items) and
      the SF-36 to 237 out of 312 patients with clinically definite multiple sclerosis
      with EDSS<or=6.5. The EMIF-SEP is composed of four dimensions (cognitive,
      physical, social role and psychological) and allows a multidimensional
      evaluation. Using a multivariate analysis, EMIF-SEP total scores with physical
      and social role subscales were highly correlated with EDSS (p < 0.0001).
      Cognitive and psychological dimensions of the EMIF-SEP were not linked to EDSS.
      EMIF-SEP was not correlated with disease course after adjusting for EDSS. EMIF
      SEP scores were significantly associated with depression scores (r = 0.74, p <
      0.0001). The multivariate analysis also showed a significant impact of fatigue on
      each scale of quality of life of the SF-36. These data confirm that fatigue is
      correlated with disability, but cognitive and psychological dimensions of fatigue
      remain independent. Fatigue is also associated with depression and quality of
      life.

PMID- 16434058
TI  - Comparison of rat dopamine D2 receptor occupancy for a series of antipsychotic
      drugs measured using radiolabeled or nonlabeled raclopride tracer.
AB  - Preclinical brain receptor occupancy measures have heretofore been conducted by
      quantifying the brain distribution of a radiolabeled tracer ligand using either
      scintillation spectroscopy or tomographic imaging. For smaller animals like
      rodents, the majority of studies employ tissue dissection and scintillation
      spectroscopy. These measurements can also be accomplished using liquid
      chromatography coupled to mass spectral detection to measure the brain
      distribution of tracer molecules, obviating the need for radioligands. In order
      to validate mass spectroscopy-based receptor occupancy methods, we examined
      dopamine D2 receptor dose-occupancy curves for a number of antipsychotic drugs in
      parallel experiments using either mass spectroscopy or radioligand-based
      approaches. Oral dose-occupancy curves were generated for 8 antipsychotic
      compounds in parallel experiments using either radiolabeled or unlabeled
      raclopride tracer. When curves generated by these two methods were compared and
      ED(50) values determined, remarkably similar data were obtained. Occupancy ED(50)
      values were (mg/kg): chlorpromazine, 5.1 and 2.7; clozapine, 41 and 40;
      haloperidol, 0.2 and 0.3; olanzapine, 2.1 and 2.2; risperidone, 0.1 and 0.4;
      spiperone, 0.5 and 0.4; thioridazine 9.2 and 9.5; and ziprasidone 1.4 and 2.1
      (unlabeled and radiolabeled raclopride tracer, respectively). The observation
      that in vivo application of both techniques led to comparable data adds to the
      validation state of the mass spectroscopy-based approach to receptor occupancy
      assays.

PMID- 16434059
TI  - Effects of lipopolysaccharide on blood-brain barrier permeability during
      pentylenetetrazole-induced epileptic seizures in rats.
AB  - We investigated the effects of lipopolysachharide (LPS) on functional and
      structural properties of the blood-brain barrier (BBB) during pentylenetetrazole
      (PTZ)-induced epileptic seizures in rats. Arterial blood pressure was
      significantly elevated during epileptic seizures irrespective of LPS
      pretreatment. Plasma levels of interleukin (IL)-1, interleukin (IL)-6, nitric
      oxide (NO) and malondialdehyde (MDA) increased while catalase concentrations
      decreased in animals treated with LPS, PTZ and LPS plus PTZ. The significantly
      increased BBB permeability to Evans blue (EB) dye in the cerebral cortex,
      diencephalon and cerebellum regions of rats by PTZ-induced seizures was markedly
      reduced upon LPS pretreatment. Immunoreactivity for tight junction proteins,
      zonula occludens-1 and occludin, did not change in brain vessels of animals
      treated with PTZ and LPS plus PTZ. Glial fibrillary acidic protein
      immunoreactivity was increased in LPS, but not in PTZ and LPS plus PTZ. These
      results indicate that LPS pretreatment reduces the passage of EB dye bound to
      albumin into the brain, at least partly, by increasing plasma NO and IL-6 levels
      during PTZ-induced epileptic seizures. We suggest that LPS may provide protective
      effects on the BBB integrity during epileptic seizures through transcellular
      pathway, since the paracellular route remained unaffected by LPS and LPS plus
      PTZ.

PMID- 16434060
TI  - Altered expression of cellular membrane molecules of HLA-DR, HLA-G and CD99 in
      cervical intraepithelial neoplasias and invasive squamous cell carcinoma.
AB  - OBJECTIVE: The aim of this study was to investigate the role of HLA-DR, HLA-G and
      CD99 during cervical carcinogenesis and to examine the prognostic significance of
      these protein expressions in invasive squamous cell carcinoma (SCC). METHODS:
      Using specific antibodies for HLA-DR, HLA-G and CD99, we examined protein
      expressions in 19 normal cervix, 15 mild dysplasia (CIN I), 22 moderate dysplasia
      (CIN II), 23 severe dysplasia (CIN III), and 34 invasive squamous cell carcinoma
      by immunohistochemistry. And we detected the expression of Ki67 in the same
      specimens. RESULTS: None of normal cervix and CINs except three cases of CIN III
      expressed HLA-DR. HLA-DR expression increased progressively with the grade of the
      tumor, and significant differences could be observed between grade 1 and grade 2
      (P<0.01) and between grade 1 and grade 3 (P<0.05). In all normal epithelial
      control samples, HLA-G expression was seen in ectocervical squamous and
      endocervical columnar epithelium and the staining was strong and uniform. Only a
      small proportion of CINs and SCCs showed reduced expression of HLA-G. Compared
      with the results in the control samples, CINs and SCCs showed significantly
      reduced expression of HLA-G (P<0.001). SCCs showed significantly increased
      expression of CD99 when compared with normal cervix and CINs (P<0.05). Ki67 was
      expressed in all specimens. Significant differences were observed between CINs
      and normal cervix (P<0.001) and SCCs and controls (P<0.001), but no significant
      differences could be observed between SCCs and CINs. None of the expressions of
      these proteins was associated with any of clinicopathological parameters.
      CONCLUSIONS: These results indicate that increased expression of HLA-DR and CD99
      may be related to the evolution of cervical cancer. All protein expressions were
      not associated with clinicopathological parameters.

PMID- 16434061
TI  - Diurnal variation of arachidonoylethanolamine, palmitoylethanolamide and
      oleoylethanolamide in the brain of the rat.
AB  - The diurnal variations of the endocannabinoid arachidonoylethanolamine
      (anandamide, ANA) as well as palmitoylethanolamide (PEA) and oleoylethanolamide
      (OEA) were detected and quantified in cerebrospinal fluid (CSF), pons,
      hippocampus, and hypothalamus in the rat over 24 h using HPLC/MS. In CSF, the 3
      compounds presented an increase in their concentration during the lights-on
      period and a remarkable decrease in their values during the lights-off period. In
      the pons, ANA, PEA and OEA showed the maximum values during the dark phase. On
      the other hand, we found that in the hippocampus, ANA increased its concentration
      during the lights-off period and PEA showed the highest peak at the beginning of
      the same period. OEA concentration showed no diurnal variations in the
      hippocampus. Finally, in the hypothalamus, ANA rose during the lights-on period
      whereas PEA and OEA presented the highest concentration at the end of the lights
      off period. We postulate that all compounds are likely to be accumulated in
      parenchyma during the lights-off period (when animal is awake) and then, released
      into the CSF in order to reach target regions in turn to modulate diverse
      behaviors, such as feeding and sleep.

PMID- 16434062
TI  - Non-invasive evaluation of endothelial dysfunction in uncomplicated obesity:
      relationship with insulin resistance.
AB  - Obesity is associated with increased cardiovascular morbidity and amortality.
      Endothelial dysfunction, involved in the pathogenesis of cardiovascular events,
      has been demonstrated in obese patients with invasive techniques requiring artery
      catheterization. The aim of our investigation was to evaluate, with a non
      invasive method readily employable on clinical grounds, impaired vasodilatation
      and its relationship with insulin resistance in uncomplicated obesity. 15
      uncomplicated obese subjects (BMI = 36.6 +/- 3.2) and 10 lean controls (BMI =
      22.9 +/- 1.25) were enrolled in this study. All subjects underwent measurement of
      endothelium-dependent (FBFr) vasodilatation by forearm venous occlusion
      pletysmography after increasing times of ischemia, and measurement of insulin
      sensitivity by the euglycemic hyperinsulinemic clamp technique (M index), by
      fasting glucose and insulin (HOMA-IR) and by oral glucose tolerance test (ISI
      index). Endothelium-independent (N-FBFr) vasodilatation was assessed as well. The
      FBFr was markedly blunted in obese patients versus lean controls (30 s: 2.12 +/-
      0.34 vs. 3.63 +/- 0.22, P < 0.01; 60 s: 2.34 +/- 0.42 vs. 3.82 +/- 0.53, P <
      0.01; 180 s: 3.20 +/- 0.45 vs. 7.15 +/- 0.35, P < 0.01; 300 s: 4.08 +/- 0.94 vs.
      14.1 +/- 0.82, P < 0.001). The N-FBFr was not different in the two groups. High
      correlation was found between M index and FBFr at all ischemia times. HOMA-IR and
      ISI were not related with FBFr. The non-invasive evaluation of endothelial
      dysfunction by a simple and reliable method based on venous occlusive
      plethysmography shows high correlation between impaired endothelium-dependent
      vasodilatation and insulin resistance in uncomplicated obesity. This non-invasive
      test of endothelial function may be routinely performed in the assessment of
      cardiovascular risk in uncomplicated obesity.

PMID- 16434063
TI  - Investigation of the SSRI augmentation properties of 5-HT(2) receptor antagonists
      using in vivo microdialysis.
AB  - Recent evidence that 5-HT(2) receptors exert a negative influence on central 5
      hydroxytryptamine (5-HT) neurones suggests that 5-HT(2) receptor antagonists may
      augment the effects of serotonin selective reuptake inhibitors (SSRIs). The
      present study investigated whether pre-treatment with 5-HT(2) receptor
      antagonists enhances the effect of SSRI administration on hippocampal
      extracellular 5-HT of freely moving rats. Administration of the SSRI citalopram
      at a low (2mg kg(-1)) and higher (4 mg kg(-1)) dose, increased dialysate 5-HT by
      5- and 8-fold, respectively. Pre-treatment with the 5-HT(2) receptor antagonist
      ketanserin (4 mg kg(-1)) augmented the effect of 4 mg kg(-1) but not 2mg kg(-1)
      citalopram. The effect of 4 mg kg(-1) citalopram was also augmented by pre
      treatment with either the 5-HT(2C) receptor antagonist SB 242084 (0.5mg kg(-1))
      or the 5-HT(2A) receptor antagonist MDL 100907 (0.5mg kg(-1)). As with
      citalopram, fluoxetine elevated dialysate 5-HT at both a low (5mg kg(-1)) and
      higher (20mg kg(-1)) dose. However, neither dose of fluoxetine was augmented by
      ketanserin (4 mg kg(-1)). These results confirm recent findings that 5-HT(2)
      receptor antagonists augment the effect of citalopram on extracellular 5-HT, and
      indicate the involvement of 5-HT(2C) and possibly 5-HT(2A) receptors. The lack of
      augmentation of fluoxetine might reflect the intrinsic 5-HT(2) receptor
      antagonist properties of this drug.

PMID- 16434064
TI  - Postnatal development of P2 receptors in the murine gastrointestinal tract.
AB  - The actions of purine and pyrimidine compounds on isolated segments of the mouse
      intestine were investigated during postnatal development. The localization of
      P2Y(1), P2Y(2), P2Y(4), P2X(1,) P2X(2) and P2X(3) receptors were examined
      immunohistochemically, and levels of expression of P2Y(1), P2X(1) and P2X(2) were
      studied by Western immunoblot. From day 12 onwards, the order of potency for
      relaxation of longitudinal muscle of all regions was 2-MeSADP>or=alpha,beta
      meATP>or=ATP=UTP=adenosine, suggesting P2Y(1) receptors. This was supported by
      the sensitivity of responses to 2-MeSADP to the selective antagonist MRS 2179 and
      P2Y(1) receptor immunoreactivity on longitudinal muscle and a subpopulation of
      myenteric neurons. A further alpha,beta-meATP-sensitive P2Y receptor subtype was
      also indicated. ATP and UTP were equipotent suggesting a P2Y(2) and/or P2Y(4)
      receptor. Adenosine relaxed the longitudinal muscle in all regions via P1
      receptors. The efficacy of all agonists to induce relaxation of raised tone
      preparations increased with age, being comparable to adult by day 20, the weaning
      age. During postnatal development the contractile response of the ileum and colon
      was via P2Y(1) receptors, while the relaxant response mediated by P2Y(1)
      receptors gradually appeared along the mouse gastrointestinal tract, being
      detectable in the stomach from day 3 and in the duodenum from day 6. In the ileum
      and colon relaxant responses to 2-MeSADP were not detected until days 8 and 12,
      respectively. 2-MeSADP induced contractions on basal tone preparations from day
      3, but decreased significantly at day 12 and disappeared by day 20. At day 8,
      contractions of colonic longitudinal muscle to ATP showed no desensitisation
      suggesting the involvement of P2X(2) receptors. Immunoreactivity to P2X(2)
      receptors only was observed on the longitudinal muscle of the colon and ileum
      from day 1 and on a subpopulation of myenteric neurons from day 3. These data
      suggest that P2Y(1) receptors undergo postnatal developmental changes in the
      mouse gut, with a shift from contraction to relaxation. Such changes occur 1 week
      before weaning and may contribute to the changes that take place in the gut when
      the food composition changes from maternal milk to solid food.

PMID- 16434067
TI  - Hemisphere asymmetry for imitation of hand and finger movements, Goldenberg's
      hypothesis reworked.
AB  - Goldenberg and co-workers put forward the hypothesis that coding of hand gestures
      with respect to body parts depends upon the functioning of the left hemisphere
      while the right hemisphere would be involved in imitation of finger postures.
      They supported this claim with experimental evidence from lesion studies,
      however, they failed to back it up with functional neuroimaging data. To verify
      Goldenberg's hypothesis on hemisphere asymmetries for hand/finger postures
      imitation, the performance of 35 patients with left hemisphere lesion (L/pts), of
      24 patients with right hemisphere lesion (R/pts) and that of 41 matched controls
      was assessed in two imitation tasks, respectively, taxing hand or finger
      postures. The data, adjusted for the performance of the controls and for the
      effect of age were analysed using a multivariate, nonparametric approach. The
      outcome partly supports Goldenberg and colleagues' hypothesis: hand minus finger
      performance did differs between the R/pts and L/pts patients, even considering
      the pertinent hand-finger performances by control participants, however, in line
      with neuroimaging evidence, the left hemisphere's contribution is greater than
      that of the right for both finger and hand posture imitation.

PMID- 16434066
TI  - Bias in magnitude estimation following left hemisphere injury.
AB  - There is a growing interest both in identifying the neural mechanisms of
      magnitude estimation and in identifying forms of bias that can explain aspects of
      behavioral syndromes like unilateral neglect. Magnitude estimation is associated
      with activation of temporo-parietal cortex in both cerebral hemispheres of normal
      subjects; however, it is unclear if and how left hemisphere lesions bias
      magnitude estimation because the infrequency of neglect and the presence of
      aphasia in these subjects confound examination. In contrast, we examined
      magnitude estimation using 12 different types of sensory stimuli that spanned
      five sensory domains in two patients with very different clinical presentations
      following unilateral left hemisphere stroke. One patient had neglect sub-acutely
      without aphasia. The other had aphasia chronically after a temporo-parietal
      lesion but not neglect. The neglect patient was re-examined 48 h after being
      treated with modafinil (Provigil) for decreased arousal. Both patients
      demonstrated bias in magnitude estimation relative to normal subjects (n=83).
      Alertness improved in the neglect patient after taking modafinil. His neglect
      also resolved and his magnitude estimates more closely resembled those of normal
      subjects. This is the first evidence, to our knowledge, that left hemisphere
      injury can bias magnitude estimation in a manner similar but not identical to
      that associated with right hemisphere injury.

PMID- 16434065
TI  - Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated
      rotational behavior but not L-DOPA-induced abnormal involuntary movements in the
      unilateral dopamine-depleted rat.
AB  - Previous experiments have demonstrated that serotonin (5-HT) 2A receptor
      antagonists suppress hyperkinetic behaviors associated with dopamine (DA) D1
      receptor supersensitivity in rats with 6-hydroxydopamine (6-OHDA) lesions. Since
      l-DOPA induced dyskinesia (LID) may be mediated by over-sensitive D1-mediated
      signaling, the present study examined the effects of the selective 5-HT2A
      antagonist M100907 on LID behaviors in DA-depleted rats. Adult male Sprague
      Dawley rats with unilateral 6-OHDA lesions received daily l-DOPA treatments to
      produce dyskinetic behaviors as measured by abnormal involuntary movements (AIMs)
      testing. In these animals, M100907 (0.01, 0.1 or 1.0mg/kg, ip) given 30 min
      before l-DOPA did not alter the appearance or intensity of AIMs behaviors.
      Because l-DOPA induced AIMs in rats are dependent upon D1 and D2 receptor
      activation, a second study was performed to determine if M100907 could suppress
      D1- or D2-mediated rotational behaviors. Contralateral rotations induced by the
      D1 agonist SKF82958 were significantly reduced by pre-treatment with M100907.
      However, M100907 was ineffective in reducing rotations induced by the D2 agonist
      quinpirole. The finding that M100907 suppresses rotations induced by D1, but not
      D2, agonists may provide a partial explanation for the lack of effect of a
      selective 5-HT2A antagonist on l-DOPA-induced AIMs behaviors.

PMID- 16434068
TI  - Intake, sweetness and liking during modified sham feeding of sucrose solutions.
AB  - Although sweet solids and liquids are palatable to humans and ingested frequently
      when readily available, the quantitative relationship between sweet taste and
      intake has not been reported in humans. To investigate the quantitative
      relationship between sweet taste and intake directly, we adapted the modified
      sham feeding technique, previously used in humans for the study of the orosensory
      control of autonomic, neuroendocrine, and metabolic mechanisms, to measure the
      intake of solutions both unsweetened and sweetened with four concentrations of
      sucrose. By limiting the sucrose stimuli to the mouth, the modified sham feeding
      technique measures the orosensory stimulation of intake by sucrose in the absence
      of inhibitory postingestive stimulation. Nine healthy women were randomly
      presented with two series of five solutions of cherry Kool Aid unsweetened or
      sweetened with one of four concentrations of sucrose (2.5%, 5%, 10%, or 20%) in a
      closed opaque container fitted with a straw. They were instructed to sip as much
      as they wanted of the liquid during 2-min trials and to spit the fluid out into
      another opaque container. At the end of each trial, they used Visual Analogue
      Scales to rate the perceived intensities of sweetness and liking of the liquid
      that they had just sipped and spit. Intake, liking and perceived sweetness were
      significantly affected by sucrose concentration (p values</=0.038). Intake at 20%
      was not significantly larger than 10% or 5%. The effects of sucrose were
      presumably due to orosensory stimulation in the absence of postingestive
      stimulation because the amount of liquid spit out did not differ significantly
      from the amount sipped.

PMID- 16434069
TI  - Volatile oil from Guarea macrophylla ssp. tuberculata: seasonal variation and
      electroantennographic detection by Hypsipyla grandella.
AB  - GC and GC-MS analyses of the volatile oils from Guarea macrophylla (Meliaceae)
      collected during three different periods in one year (February, June and October)
      indicated a seasonal variation in chemical composition. Whilst sesquiterpenes
      were the predominant class of components present in the leaf oil, a seasonal
      dependent variation in the degree of oxygenation of these compounds was detected,
      which seemed to be associated with phenological factors. The leaf oil, and
      fractions thereof, were subjected to GC coupled with electroantennographic
      detection employing antennae of females of Hypsipyla grandella, an insect pest
      that attacks several meliaceous species. Five compounds elicited significant
      responses and these were identified as ledol, 1-cubenol, guai-6-en-10beta-ol, 1
      epi-cubenol, and tau-muurolol. The results suggest that these components could be
      responsible for the attraction of H. grandella to G. macrophylla.

PMID- 16434070
TI  - A hemiterpene glucoside as a probing deterrent of the bean aphid, Megoura
      crassicauda, from a non-host vetch, Vicia hirsuta.
AB  - The bean aphid, Megoura crassicauda Mordvilko, feeds selectively on plants
      belonging to the genus Vicia (Fabaceae). However, it never infests the tiny
      vetch, V. hirsuta (L.) Gray. The aphid appeared to discriminate between host and
      non-host plants by tasting specific chemicals during penetration of its stylet
      into the plant tissues. The aphid, after being stimulated by specific probing
      stimulants, deposited characteristic proteinous stylet sheaths through a parafilm
      membrane, which has one side in contact with an extract solution of Vicia
      angustifolia. However, an addition of a V. hirsuta extract to the medium strongly
      inhibited the salivary sheath formation. A specific probing deterrent was
      isolated from a V. hirsuta extract by monitoring the inhibitory effect, and
      identified as (E)-2-methyl-2-butene-1,4-diol 4-O-beta-d-glucopyranoside. A
      mixture of the glycoside and the stimulatory V. angustifolia fraction in the same
      equivalency found in plants significantly decreased the probing activity in M.
      crassicauda. Since the stylet insertion process is a crucial step for the aphid's
      settlement on a plant, the glycoside seems to act as an effective chemical
      barrier for V. hirsuta.

PMID- 16434071
TI  - Antimicrobial monomeric and dimeric diterpenes from the leaves of Helichrysum
      tenax var tenax.
AB  - The hexane extract of fresh air-dried leaves of Helichrysum tenax (Asteraceae)
      afforded ent-beyer-15-en-19-ol (1), its 4-epimer ent-beyer-15-en-18-ol (2),
      15beta,16beta-epoxide-ent-beyeran-19-ol (3), as well as (4) consisting of two
      units of (1) linked as a diester of malonic acid, and (5), a compound. Its
      constituents are (1) and (3) also linked as a diester of malonic acid. The leaves
      of the plant are densely covered in fine glandular trichomes. These are extremely
      sticky and exude a mixture of the above diterpenes. Antimicrobial tests showed
      that (1), in particular, was highly active (3.1 and 3.6 microg/ml) against
      Bacillus cereus and Staphylococcus epidermidis, respectively.

PMID- 16434073
TI  - Mass spectrometric and toxicological assays of Athabasca oil sands naphthenic
      acids.
AB  - This work concerns the analysis of model naphthenic acids and authentic
      naphthenic acids from the tailings ponds of the Athabasca tar sands. A first
      objective was to compare atmospheric pressure chemical ionization mass
      spectrometry (APCI-MS) with the previously studied electrospray mass spectrometry
      (ESI-MS) in this analysis. APCI-MS had a wider range of quantitation than ESI-MS,
      but its detection limit was poorer and model compounds showed greater variation
      in calibration sensitivity. A second objective was fractionation of naphthenic
      acids from tailings pond water and analysis by the Microtox toxicity assay.
      Fractionation on the basis of solubility gave fractions that did not differ
      significantly either in their congener distribution by ESI-MS or in their
      response to the Microtox assay. When partial separation was achieved by anion
      exchange chromatography, fractions with a higher proportion of multi-ring
      structures exhibited lower toxic potency. This finding is consistent with field
      observations that indicate that the toxic potency of tailings ponds water
      declines as the samples age-multi-ring structures are more highly branched and
      therefore more resistant to microbial degradation.

PMID- 16434072
TI  - Vasodilatory and hypoglycaemic effects of two pyrano-isoflavone extractives from
      Eriosema kraussianum N. E. Br. [Fabaceae] rootstock in experimental rat models.
AB  - Zulu traditional health practitioners have claimed that the roots of Eriosema
      kraussianum N. E. Br. (Fabaceae) and other Eriosema species (Zulu indigenous
      umbrella name of "uBangalala") are effective remedies for the treatment of
      erectile dysfunction (ED) and/or impotence. In order to scientifically appraise
      the significance and contribution of Eriosema kraussianum to its ethnomedical use
      as "uBangalala" and "VIAGRA substitute", the present study was undertaken to
      investigate the vasodilatory and hypoglycaemic properties of the two main
      bioactive chemical compounds obtained from E. kraussianum, in experimental rat
      models, using sildenafil citrate (VIAGRA) as the reference drug for comparison.
      The two E. kraussianum rootstock constituents (K1 and K2, 20-80 mg/kg p.o.)
      caused dose-dependent and significant (P<0.05-0.001) hypoglycaemia in rats.
      Relatively low to high concentrations of the plant's extracts (K1 and K2, 100
      2000 microg/ml) always produced biphasic effects on rat isolated portal veins. K1
      and K2-provoked responses of the isolated portal veins always consisted of
      concentration-related initial transient, but significant (P<0.05), contractions
      of the venous muscle preparations, followed by secondary, longer-lasting, highly
      significant (P<0.01-0.001) relaxations of the venous muscle strips. Sildenafil
      citrate (VIAGRA, 5-100 microg/ml) always produced concentration-related and
      highly significant relaxations of the rat isolated portal veins. Unlike K1 and K2
      (20-80 mg/kg p.o.), however, sildenafil citrate (VIAGRA, 100 mg/kg p. o.) only
      caused slight and insignificant (P>0.05) reductions in the blood glucose levels
      of the experimental animals used. On the other hand, glibenclamide (10 mg/kg
      p.o.) induced highly significant (P<0.05-0.001), marked reductions in the blood
      glucose concentrations of the rats. The findings of this laboratory animal study
      indicate that the two hydro-ethanol extractives of E. kraussianum (K1 and K2)
      possess hypoglycaemic and secondary, vasorelaxant effects in the experimental
      paradigms used.

PMID- 16434074
TI  - Optical density and photonic efficiency of silica-supported TiO2 photocatalysts.
AB  - Over the last years, many research groups have developed supported TiO2-based
      materials in order to improve the engineering applications of photocatalytic
      technologies. However, not many attempts have been made to evaluate the optical
      behavior of these materials. This work focuses on the study of the photonic
      efficiencies of silica-supported TiO2 photocatalysts following the
      photodegradation of dichloroacetic acid (DCA) as model compound. Catalysts with
      different types of silica support and titania loadings were tested and their
      activity was found to be in correlation with the results of the clusters size
      distribution of the TiO2 nanocrystals. The photonic efficiency of the supported
      photocatalysts depends extremely on the optical density of the solid suspensions.
      Influence of the textural properties of the support and the titania loading on
      the optical density as well as on the photonic efficiency of the materials are
      discussed. The dependence of the absorption of radiation by the suspension on the
      catalyst concentration is also analyzed.

PMID- 16434075
TI  - Evaluation of data from the literature on the transport and survival of
      Escherichia coli and thermotolerant coliforms in aquifers under saturated
      conditions.
AB  - Escherichia coli and thermotolerant coliforms are of major importance as
      indicators of fecal contamination of water. Due to its negative surface charge
      and relatively low die-off or inactivation rate coefficient, E. coli is able to
      travel long distances underground and is therefore also a useful indicator of
      fecal contamination of groundwater. In this review, the major processes known to
      determine the underground transport of E. coli (attachment, straining and
      inactivation) are evaluated. The single collector contact efficiency (SCCE),
      eta0, one of two parameters commonly used to assess the importance of attachment,
      can be quantified for E. coli using classical colloid filtration theory. The
      sticking efficiency, alpha, the second parameter frequently used in determining
      attachment, varies widely (from 0.003 to almost 1) and mainly depends on charge
      differences between the surface of the collector and E. coli. Straining can be
      quantified from geometrical considerations; it is proposed to employ a so-called
      straining correction parameter, alpha(str). Sticking efficiencies determined from
      field experiments were lower than those determined under laboratory conditions.
      We hypothesize that this is due to preferential flow mechanisms, E. coli
      population heterogeneity, and/or the presence of organic and inorganic compounds
      in wastewater possibly affecting bacterial attachment characteristics. Of equal
      importance is the inactivation or die-off of E. coli that is affected by factors
      like type of bacterial strain, temperature, predation, antagonism, light, soil
      type, pH, toxic substances, and dissolved oxygen. Modeling transport of E. coli
      can be separated into three steps: (1) attachment rate coefficients and straining
      rate coefficients can be calculated from Darcy flow velocity fields or pore water
      flow velocity fields, calculated SCCE fields, realistic sticking efficiency
      values and straining correction parameters, (2) together with the inactivation
      rate coefficient, total rate coefficient fields can be generated, and (3) used as
      input for modeling the transport of E. coli in existing contaminant transport
      codes. Areas of future research are manifold and include the effects of typical
      wastewater characteristics, including high concentrations of organic compounds,
      on the transport of E. coli and thermotolerant coliforms, and the upscaling of
      experiments to represent typical field conditions, possibly including
      preferential flow mechanisms and the aspect of population heterogeneity of E.
      coli.

PMID- 16434076
TI  - Characterization of organic compounds in aerosol particles from a coniferous
      forest by GC-MS.
AB  - Atmospheric aerosol particles were collected in a Finnish Scots pine forest as
      part of a European Union project. Sampling was done in March-April 2003 with a
      high-volume sampler. Dynamic ultrasonic-assisted solvent extraction and gas
      chromatography-mass spectrometry (GC-MS) were applied to the analysis of aerosol
      samples for analytes such as n-alkanes, polycyclic aromatic hydrocarbons (PAH),
      oxidized polycyclic aromatic hydrocarbons (oxy-PAHs), sesquiterpenes (SQT) and
      oxidized sesquiterpenes (oxy-SQT). The highest concentrations were found for the
      n-alkanes, which were present in a wide range (C11-C32) indicating both biogenic
      and anthropogenic sources. PAH compounds were found in every sample while oxy-PAH
      compounds were present in low concentrations in a few samples. A few oxidized
      monoterpenes, most notably (-)-verbenone and pinonaldehyde, were found in several
      samples in concentrations clearly exceeding the PAH concentrations. The effect of
      temperature could be seen in most samples, where the concentrations of n-alkanes
      declined with decreasing temperatures. Particle formation events were accompanied
      by higher concentrations of heavy n-alkanes, verbenone and pinonaldehyde.

PMID- 16434077
TI  - Contrasting behaviour of cadmium and zinc in a soil-plant-arthropod system.
AB  - This study investigates the transfer of Cd and Zn from a soil amended with sewage
      sludge at rates up to 100 t ha(-1) through a multi-trophic system consisting of
      barley, the aphid Sitobion avenae and the larvae of the lacewing Chrysoperla
      carnae. Results show marked differences in the transfer of the two metals.
      Cadmium was freely accumulated in barley roots, but accumulation in the shoot was
      restricted to a concentration of around 0.22 mg kg(-1) (dry weight). This limited
      the transfer of Cd to higher trophic levels and resulted in no significant
      accumulation of Cd in S. avenae or in C. carnae. Zinc transfer in the system was
      largely unrestricted, resulting in significant accumulation in roots and shoots,
      in S. avenae and in C. carnae. Cadmium biomagnification occurred in lacewing
      pupae, with concentrations up to 3.6 times greater than in aphids. S. avenae
      biomagnified Zn by a factor of ca. 2.5 at low sludge amendment rates, but
      biomagnification decreased to a factor of 1.4 at the highest amendment rate.
      Biomagnification of Zn did not occur in C. carnae, but concentrations were up to
      3.5 time higher than in soil. Results are discussed in light of the mechanisms
      regulating transfer of the two metals in the system.

PMID- 16434078
TI  - Fractionation and extractability of sulfur, iron and trace elements in sulfidic
      sediments.
AB  - This study describes iron and sulfur fractionation, and the related
      extractability of selected trace elements (As, Cd, Cr, Cu, Ni, Pb and Zn) in
      estuarine sediments. The sediments were sulfidic, with moderately high
      concentrations of pore-water sulfide (200-600 micromol l(-1)) and acid-volatile
      sulfide (AVS; 9.9-129 micromol g(-1)). Pyrite-S concentrations increased with
      depth, with 63-251 micromol g(-1) at site W1 and 312-669 micromol g(-1) at site
      W2. The degree of sulfidisation was generally high (>80%), indicating that Fe may
      be limiting pyrite accumulation. The ratios of AVS to pyrite-S increased with
      sediment depth, as expected for the pyritisation of solid-phase AVS. Cadmium, Pb
      and Zn extractability in 1M HCl indicated that these elements are not
      significantly sequestered during pyritisation, whereas sequestration may be
      important for As, Cu and possibly Ni. Extractability trends for Cr suggest that
      diagenesis in sulfidic sediments may enhance Cr reactivity. Overall, replacement
      of AVS by pyrite during diagenesis may enhance the reactivity of Cd, Cr, Pb and
      Zn, whereas As, Cu and possibly Ni may be rendered less reactive.

PMID- 16434079
TI  - Status of the PCDD and PCDF contamination of commercial milk caused by milk
      cartons.
AB  - Within the scope of this study, possible migration of polychlorinated
      dibenzodioxins and -furans (PCDDs/PCDFs) from cartons (produced using bleached
      cardboard) into cow's milk was investigated. Three different types of carton were
      examined. The milk samples were taken at different times of storage and analysed
      for PCDDs/PCDFs. In contrast to a similar study carried out in 1990, the I-TEQ
      results of all cartons analysed may be considered very low. No significant
      migration of toxic (2,3,7,8-chlorine-substituted) PCDDs/PCDFs could be observed.
      This is due to the very low PCDD/PCDF concentrations in modern cardboards as a
      result of the elemental chlorine-free (ECF) bleaching processes used. As far as
      the milk samples are concerned, no influence of the cardboards (according to the
      I-TEQ data) could be ascertained. I-TEQ concentrations in milk did not noticeably
      change during storage times of three, six and eight days. The I-TEQ-data obtained
      for all milk samples was found to be in the range typical of background
      concentrations in cow's milk in Germany. Although 1,2,7,8-TCDF is not included in
      the calculation of the TEQ (no 2,3,7,8-chlorine-substitution), analysis of this
      congener in cardboard samples was also carried out as a matter of general
      interest for cardboard investigations and an indicator of pulp bleaching with
      free chlorine.

PMID- 16434080
TI  - Predicting low biota to sediment accumulation factors of PAHs by using infinite
      sink and equilibrium extraction methods as well as BC-inclusive modeling.
AB  - Sequestration of polycyclic aromatic hydrocarbons (PAHs) results in the slow
      release of PAHs from sediment to the aqueous environment, thus limiting
      bioavailability. Three methods to account for the limited bioavailability of
      native PAHs to the gastropod Hinia reticulata were therefore investigated: (i)
      infinite-sink extractions that measure desorption; (ii) equilibrium extractions
      that measure freely dissolved pore water concentrations and (iii) black carbon
      inclusive modeling. The rapidly desorbing fraction was estimated based on the
      amount desorbed by Tenax. Relatively small amounts of PAHs (<9%) were present in
      F(rapid) and the observed solid-water distribution ratios (K(d,obs)) were
      approximately 1-2 orders of magnitude higher than literature K(oc) values. Biota
      to sediment accumulation factors (BSAFs) measured in the gastropod H. reticulata
      ranged from 0.02 to 0.07, 10-140 times lower than the theoretical value of
      approximately 1-2. The BSAFs calculated using the rapidly desorbing fraction or
      freely dissolved aqueous concentrations were also much lower than the theoretical
      value, and median values differed from the measured BSAFs by only a factor of 1.5
      9. Furthermore, the result of using a BC-inclusive BSAF model could explain the
      deviation from the theoretical BSAF value and account for the low bioavailability
      of these native PAHs to H. reticulata. Risk assessment strategies of in situ
      contamination should therefore include a combination of chemical methods
      accounting for bioavailability, as well as bioaccumulation studies.

PMID- 16434081
TI  - Levels and trends of brominated flame retardants in the European environment.
AB  - In this paper, we review those data which have recently become available for
      brominated flame retardants (particularly the brominated diphenyl ethers (BDEs)
      and hexabromocyclododecane (HBCD)) in samples from the European environment.
      Environmental compartments studied comprise the atmosphere, sediments and soils,
      sewage sludges, and a variety of biological samples and food chains. This is
      currently a very active research area, and we cite over 70 studies reported in
      the literature during 2003-04. Findings include that the input of BDEs
      (especially BDE209) to the Baltic Sea by atmospheric deposition now exceeds that
      of PCBs by a factor of almost 40 times. Sewage sludge samples from both
      industrial and background locations show concentrations of BDEs, HBCD and
      tetrabromobisphenol-A (TBBP-A) that are of a similar order, indicating that the
      major source is from diffuse leaching from products into wastewater streams from
      users, households and industries generally. Point-sources from industries using
      BFRs (e.g. the textile industry) also generate local hot-spots. Sediment core
      studies identified the presence of two of the three PBDE formulations. The penta
      mix formulation was clearly present from the beginning of the 1970s, but the deca
      mix only appeared in the late 1970s. BDE183, BDE209 and HBCD were detected in
      peregrine falcons from Sweden and other birds feeding on terrestrial food chains.
      BDEs are found widely distributed in fish, including those from high mountain
      lakes in Europe, as a consequence of long-range atmospheric transport and
      deposition. A temporal trend study in archived freeze-dried mussels from the
      Seine estuary, France, indicated an exponential increase in BDE concentrations
      during the period 1982-1993, which levelled off in 1999 and 2001 and then began
      to decline after 2002. HBCD was detected in liver and blubber samples from
      harbour seals and harbour porpoises from the Wadden and North Seas, though very
      few animals yielded positive values for TBBP-A. There are difficulties in
      comparing data on summation operatorBDE from studies in which different suites of
      BDE congeners have been determined, and we suggest a common suite which will
      allow the study of all three commercial PBDE formulations.

PMID- 16434082
TI  - Brominated flame retardant concentrations and trends in abiotic media.
AB  - BFR burdens in abiotic media have been less studied than in biota, despite their
      essential value as an aide to identifying sources, temporal and geographic trends
      and exposure routes. Many polymer products consist of several percent by weight
      of BFRs. Global trade in these can result in rapid and wholesale BFR movement.
      Loss from in-use products of nonreactive BFRs may be important, particularly in
      respect to indoor exposure. In the case of BDE-209, discharges from publicly
      owned treatment works may be substantial. BFR burdens in air, water and sewage
      sludge respond rapidly to changes in environmental BFR inputs. PBDEs have been
      the most widely studied. In many locales PBDE burdens in these media now surpass
      those of PCBs. Air and water near sources and urban areas are typically enriched
      relative to rural locales. The more volatile PBDEs dominate in the vapor phase,
      while BDE-209 typically predominates on particulates. Evidence exists for long
      range transport of the more volatile PBDEs. A greater diversity of BFRs (mostly
      PBDEs, HBCD and TBBP-A) has been detected in sewage sludges. Land application of
      these sludges on agricultural fields is one conduit for soil contamination. In
      general, environmental concentrations of BDE-209 appear to be increasing, while
      penta-BDE burdens in Europe may have peaked. Sediments function as longer-term
      integrators of environmental burdens. Concentrations of common BFRs therein may
      be substantial near point sources. Evidence for debromination in the environment
      has been limited to date. However, some laboratory and field observations suggest
      it is possible to a limited extent.

PMID- 16434083
TI  - Simultaneous proteomic profiling of four different growth states of human
      fibroblasts, using amine-reactive isobaric tagging reagents and tandem mass
      spectrometry.
AB  - In general, permanent growth arrest due to exhaustive cell replication can be
      induced prematurely by either stress or overexpression of selected oncogenes. In
      an attempt to examine key proteins involved in achieving premature senescence,
      and how they differ from those in serially passaged, replicatively exhausted
      cells, we used a novel proteomic profiling approach, isobaric tagging for
      relative and absolute quantitation (iTRAQ), to perform simultaneous four-way
      comparison of replicatively senescent fibroblasts, oxidatively stressed
      prematurely senescent fibroblasts, and their young replicating and quiescent
      counterparts. Two hundred and forty proteins were identified and quantified
      simultaneously; data analysis reveals: (1) groups of proteins whose expressions
      are uniformly either up- or down-regulated in all three growth arrest states; (2)
      signature proteins which may serve as candidate proteomic markers to
      differentiate the quiescent state from permanent growth arrest by either
      exhaustive replication or stress induction and (3) that while oxidative stress
      induced, prematurely senescent fibroblasts morphologically resemble their
      replicatively exhausted counterparts, they exhibit different protein expression
      patterns. Results from simultaneous proteomic profiling were validated by Western
      blotting for selected proteins: collagen type I, HSP90 and vimentin. In
      conclusion, this report shows that iTRAQ proteomic profiling is a powerful
      technique for globally mapping protein signatures for different culture growth
      states.

PMID- 16434084
TI  - Atmospheric mercury speciation in Yellowstone National Park.
AB  - Atmospheric concentrations of elemental mercury (Hg(0)), reactive gaseous Hg
      (RGM), and particulate Hg (pHg) concentrations were measured in Yellowstone
      National Park (YNP), U.S.A. using high resolution, real time atmospheric mercury
      analyzers (Tekran 2537A, 1130, and 1135). A survey of Hg(0) concentrations at
      various locations within YNP showed that concentrations generally reflect global
      background concentrations of 1.5-2.0 ng m(-3), but a few specific locations
      associated with concentrated geothermal activity showed distinctly elevated Hg(0)
      concentrations (about 9.0 ng m(-3)). At the site of intensive study located
      centrally in YNP (Canyon Village), Hg(0) concentrations did not exceed 2.5 ng m(
      3); concentrations of RGM were generally below detection limits of 0.88 pg m(-3)
      and never exceeded 5 pg m(-3). Concentrations of pHg ranged from below detection
      limits to close to 30 pg m(-3). RGM and pHg concentrations were not correlated
      with any criteria gases (SO(2), NO(x), O(3)); however pHg was weakly correlated
      with the concentration of atmospheric particles. We investigated three likely
      sources of Hg at the intensive monitoring site: numerous geothermal features
      scattered throughout YNP, re-suspended soils, and wildfires near or in YNP. We
      examined relationships between the chemical properties of aerosols (as measured
      using real time, single particle mass spectrometry; aerosol time-of-flight mass
      spectrometer; ATOFMS) and concentrations of atmospheric pHg. Based on the
      presence of particles with distinct chemical signatures of the wildfires, and the
      absence of signatures associated with the other sources, we concluded that
      wildfires in the park were the main source of aerosols and associated pHg to our
      sampling site.

PMID- 16434086
TI  - Systematic review of systemic therapy for advanced or recurrent endometrial
      cancer.
AB  - OBJECTIVE: To evaluate the chemotherapeutic options for women with advanced or
      recurrent endometrial cancer. METHODS: The MEDLINE, CANCERLIT and the Cochrane
      Library databases were searched from 1984 to March 2005 for randomized controlled
      trials (RCTs) comparing chemotherapy regimens in patients with advanced or
      recurrent endometrial cancer. Studies were included only if patients had
      measurable or evaluable disease, and/or response rates were reported. RESULTS:
      Seventeen RCTs compared regimens involving chemotherapy and/or hormonal
      therapies. Three chemotherapy trials demonstrated a statistically significant
      difference in response rates between treatment arms, but only one of these trials
      showed a modest survival advantage. The addition of cisplatin to doxorubicin in
      two RCTs significantly improved response rates (1.7- to 2.5-fold higher) but did
      not impact on survival. In two other RCTs using cisplatin and doxorubicin as
      standard therapy, the addition of paclitaxel improved response rates (57% versus
      34%) and median survival (15.3 versus 12.3 months) when combined with cisplatin
      and doxorubicin but not when combined with doxorubicin only. Toxicity was
      increased with the three-drug combination. Quality of life was assessed in one
      trial, which is currently only in abstract form. Medroxyprogesterone acetate (200
      mg/day) was effective in one RCT, particularly in patients with well
      differentiated, receptor-positive tumors. CONCLUSIONS: Combination chemotherapy
      with doxorubicin and cisplatin results in higher response rates than doxorubicin
      alone. The addition of paclitaxel to either of these regimens resulted in a small
      survival advantage in one trial using all three drugs. In light of the limited
      survival advantage associated with this regimen, the use of less toxic
      combinations of taxanes with carboplatin requires further study.
      Medroxyprogesterone acetate is useful in selected patients.

PMID- 16434087
TI  - Socioeconomic status and cervical cancer survival among older women: findings
      from the SEER-Medicare linked data cohorts.
AB  - OBJECTIVES: Tumor stage, age, and cell type are well-characterized predictors for
      cervical cancer survival; socioeconomic factors may also play an important role.
      The purpose of this study is to estimate cervical cancer survival by
      socioeconomic indicators and race/ethnicity among elderly women diagnosed with
      cervical cancer. METHODS: We studied 1251 women with cervical cancer aged 65 or
      older, identified between 1992 and 1999 from the Surveillance, Epidemiology, and
      End Results [SEER]-Medicare linked data. All women had similar access to care
      through Medicare fee-for-services insurance. A composite measure of socioeconomic
      status was created using census tract level data for poverty, education, and
      income. Cox proportional hazard modeling was used for all-cause and cervical
      cancer-specific survival analysis. RESULTS: Increased age (P < 0.0001) and
      advanced tumor stage (<0.0001) were associated with poorer all-cause and cervical
      cancer-specific survival. After adjustment for age, stage, and treatment,
      increased co-morbidity scores and having non-squamous cervical cancer were
      associated with poorer all-cause survival (P < 0.001). After adjusting for
      confounders, women receiving hysterectomy vs. no surgery or any treatment had
      significantly better all-cause and cervical cancer-specific survival.
      Socioeconomic factors were not associated with either all-cause (P for trend =
      0.79) or cervical cancer-specific (P for trend = 0.81) survival. No racial/ethnic
      differences in all-cause or cervical cancer-specific survival were observed after
      adjusting for socioeconomic factors. CONCLUSION: Among women with similar access
      to care, neither minority race/ethnicity nor poorer socioeconomic status were
      associated with poorer survival in this large sample of older women diagnosed
      with invasive cervical cancer. Presence of co-morbid conditions and treatment
      were important predictors of cervical cancer survival.

PMID- 16434085
TI  - Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer.
AB  - OBJECTIVES: In an ongoing effort to identify diagnostic ovarian cancer
      biomarkers, SEREX (serological analysis of recombinant cDNA expression libraries)
      technique was employed resulting in detection of 20 known genes, nine ESTs and
      one novel sequence. Interleukin-8 (IL-8) was one of ovarian cancer-associated
      antigens identified by SEREX screening. The objective of this study was,
      therefore, to evaluate the potential importance of circulating anti-IL-8 antibody
      as ovarian cancer biomarker. METHODS: We developed and optimized a new
      immunofluorescent bead-based assay for detection of anti-IL-8 antibody in blood
      serum. Circulating IL-8 and anti-IL-8 IgG concentrations were measured in blood
      sera from 44 patients with early stage (I-II) ovarian cancer, 50 patients with
      late stage (III-IV) ovarian cancer, 37 patients with benign pelvic masses, and 80
      healthy women using the bead-based assay. RESULTS: Our data indicate that serum
      contains IL-8 cytokine, anti-IL-8 antibody, and IL-8:anti-IL-8 complexes. We
      found that concentrations of IL-8 and anti-IL-8 antibody were elevated in sera of
      patients with ovarian cancer as compared with healthy controls. Logistic
      regression analysis of circulating concentrations of anti-IL-8 IgG in patients
      with stages I-II ovarian cancer versus healthy controls allowed for prediction of
      early ovarian cancer with 98% specificity, 65.5% sensitivity, 80.3% of patients
      correctly classified. Combining IL-8 and anti-IL-8 IgG with CA 125 resulted in
      increased classification power as compared to individual markers analyzed
      separately. CONCLUSION: Thus, IL-8 and anti-IL-8 autoantibody might potentially
      serve as additional biomarkers for ovarian cancer.

PMID- 16434088
TI  - Synergistic effects of combined therapy using paclitaxel and [90Y-DOTA]776.1 on
      growth of OVCAR-3 ovarian carcinoma xenografts.
AB  - OBJECTIVE: 776.1 is a monoclonal antibody prepared against the human ovarian
      cancer antigen CA 125 that demonstrates preferential binding to the cell
      associated form of the antigen and has shown promising results as an yttrium-90
      labeled antibody in pre-clinical studies examining the effects on tumor growth in
      a murine xenograft model of human ovarian cancer. The purpose of the present
      study was to examine the effects of combined therapy with [90Y-DOTA]776.1 and
      paclitaxel compared with monotherapy with either agent on the growth of OVCAR-3
      xenografts in nude mice. METHODS: Mice bearing OVCAR-3 xenografts were treated
      with paclitaxel alone, 50 microCi or 150 microCi [90Y-DOTA]776.1 alone, or a
      combination of both treatments. Control groups were included which consisted of a
      nonspecific antibody, MOPC-21, labeled to a similar degree, administered as
      monotherapy or in combination with paclitaxel. The effects of administration of
      radioimmunotherapy prior to or following chemotherapy were also examined.
      RESULTS: Treatment with paclitaxel and [90Y-DOTA]776.1 had a synergistic anti
      tumor effect on the growth of OVCAR-3 xenografts. Synergy was only observed when
      a tumor-specific antibody was used in radioimmunotherapy. While no difference in
      tumor growth was observed with order of dosing, reduced toxicity was seen when
      paclitaxel was administered prior to radioimmunotherapy. CONCLUSION: The
      combination of radioimmunotherapy using an anti-CA 125 monoclonal antibody and
      chemotherapy with paclitaxel was shown to be effective in an in vivo model of
      ovarian cancer and may hold promise as a treatment regimen for patients with
      ovarian cancer.

PMID- 16434089
TI  - Characterization of the antinociceptive effect of oxycodone in male and female
      rats.
AB  - A number of investigators have shown that sex plays an important role in the
      analgesic effects of opioids. Typically, the antinociceptive responsiveness to mu
      opioid agonists such as morphine is greater in male than in female rats. The
      effect of sex on kappa opioid analgesia is less known. The present study was
      conducted to examine sex-related differences in responsiveness to oxycodone
      (putative kappa/mu opioid agonist). This information is important since oxycodone
      is widely used clinically for treatment of pain. The present results indicated
      that oxycodone had a greater antinociceptive response in female rats compared to
      male rats. This sex specific responsiveness to oxycodone, however, was lost with
      chronic administration. The greater antinociception in female rats was even more
      prominent with U50,488H (selective kappa agonist). Further, low (subanalgesic)
      doses of oxycodone and U50,488H enhanced the sensitivity to pain (hyperalgesia)
      to a greater extent in male than in female rats. This is in contrast to the
      previously shown greater hyperalgesic effect of subanalgesic doses of the mu
      opioid agonist, morphine, in female than in male rats. The present findings
      suggest that sexual dimorphism in the effect of opioids is related to the opioid
      receptors on which they predominately act.

PMID- 16434090
TI  - Effects of gender and menstrual cycle phase on food-maintained responding under a
      progressive-ratio schedule in cynomolgus monkeys.
AB  - Clinical and preclinical data suggest that fluctuations in ovarian steroid
      hormones across the menstrual/estrous cycle influence spontaneous feeding
      behavior in females. The effects of gender, menstrual cycle phase, and ovarian
      hormone fluctuations on food-maintained responding under a progressive-ratio
      schedule were investigated in four female and three male cynomolgus monkeys.
      Females were studied across 21 menstrual cycles, and ovulatory cycles were
      defined by analysis of ovarian steroid hormone levels. Data were analyzed for the
      early and mid-follicular phase and the mid- and late luteal phase of the
      menstrual cycle. Progressive-ratio break points for food were significantly
      higher in males than in females (p < 0.01). However, progressive-ratio break
      points did not vary consistently as a function of menstrual cycle phase during
      ovulatory cycles. There were no systematic patterns of progressive-ratio break
      points in anovulatory menstrual cycles. Only one female monkey reached
      significantly higher break points during the mid- and late luteal phases in
      comparison to the mid-follicular phase of the menstrual cycle (p < 0.05). There
      was also a significant positive correlation between progressive-ratio break
      points and progesterone levels and a significant negative correlation with
      estradiol in that monkey. Although fluctuations in ovarian steroid hormones may
      influence food consumption under some conditions, consistent patterns of food
      maintained responding were not detected during ovulatory menstrual cycles in
      cynomolgus monkeys.

PMID- 16434091
TI  - Antinociceptive profile of salvinorin A, a structurally unique kappa opioid
      receptor agonist.
AB  - Salvinorin A, is a structurally unique, non-nitrogenous, kappa opioid receptor
      (KOP) agonist. Given the role of KOPs in analgesic processes, we set out to
      determine whether salvinorin A has antinociceptive activity in thermal and chemo
      nociceptive assays. The tail-flick assay was employed to investigate 1)
      salvinorin A's (0.5, 1.0, 2.0, and 4.0 mg/kg) dose-response and time-course (10,
      20, and 30 min) effects in a thermal nociceptive assay, and 2) the ability for
      the KOP antagonist norBNI (10.0 mg/kg) to prevent salvinorin A antinociception.
      The hotplate assay was utilized as a second thermal nociceptive measure to test
      salvinorin A's dose-response effects. The acetic acid abdominal constriction
      assay was used to study salvinorin A's dose-response and time-course (over 30
      min) effects in a chemo-nociceptive assay. Together, these studies revealed that
      salvinorin A produces a dose-dependent antinociception that peaked at 10 min post
      injection but rapidly returned to baseline. Additionally, pretreatment with the
      KOP antagonist norbinaltorphimine (norBNI) reversed salvinorin A-induced
      antinociception. These findings demonstrate that salvinorin A produces a KOP
      mediated antinociceptive effect with a short duration of action.

PMID- 16434092
TI  - Bond strength performance of different resin composites used as core materials
      around fiber posts.
AB  - OBJECTIVES: To evaluate the microtensile bond strengths of different resin
      composites used as core materials around fiber posts. METHODS: Forty DT Light
      Posts (RTD) were randomly divided into eight groups, according to the resin
      composite used. They included two core materials specifically developed for core
      build-up--Group 1: Core-Flo (Bisco Inc.) and Group 2: UniFil Core (GC Corp.);
      three hybrid composites--Group 3: Tetric Ceram (Ivoclar-Vivadent), Group 4:
      Gradia Direct (GC Corp.), Group 5: Bisfil 2B (Bisco, Inc.); and three flowable
      composites--Group 6: AEliteflo (Bisco, Inc.), Group 7: Filtek Flow (3M ESPE) and
      Group 8: UniFil Flow (GC Corp). A cylindrical plastic matrix was placed around
      the silanized post and filled with the respective resin composite. Each bonded
      post provided five to eight sticks for microtensile testing. Each stick was
      loaded to failure under tension at a cross-head speed of 0.5mm/min. One-way ANOVA
      and Tukey's test were used for statistical analysis. Scanning electron microscopy
      (SEM) was used to evaluate the interface of the fractured sticks. RESULTS: Resin
      composites exhibited a significant influence on microtensile bond strength
      (p<0.05). Core-Flo showed the highest bond strength (11.00+/-0.69 MPa) although
      it was not statistically significantly different from all groups, except from the
      flowable composites. Under SEM, all the composites adapted well to the fiber
      post, with a variable extent of voids observed along the fractured composite
      interfaces. SIGNIFICANCE: Although good adaptation to the post surface was
      achieved, bond strength to fiber post remains relatively weak. Core build-up and
      hybrid composites are better alternatives to flowable composites as core build-up
      materials.

PMID- 16434093
TI  - Micro-tensile bond strength to surface and subsurface enamel.
AB  - Testing of bond strength to enamel has been undertaken on both surface and
      subsurface enamel on the assumption that it is the same substrate. Over recent
      years, the micro-tensile method has become widely used for the evaluation of
      dental adhesives. However, there have been no micro-tensile bond strength studies
      comparing surface and subsurface enamel using orthodontic adhesives. It has been
      proposed that the bond strength to subsurface enamel is greater than that to
      surface enamel. OBJECTIVE: The micro-tensile bond strength (MTBS) of Transbond
      (light activated paste, 3 M Unitek, USA) to surface and subsurface enamel was
      investigated. METHODS: Ten sound freshly extracted lower human first molars were
      divided into two groups of five each. Surface enamel of the first group was
      removed with 500-grit silicone carbide paper, whilst in the second group it was
      left intact. Gelatin capsules filled with Transbond composite paste were bonded
      perpendicular to the enamel using light cure adhesive Primer (Transbond XT, 3 M
      Unitek, USA) in both groups, and stored in distilled water at 37 degrees C for 24
      h. Crowns of all specimens were sectioned bucco-lingually into vertical slabs of
      approximately 0.6 mm thickness. Slabs in each group were prepared into an
      hourglass shape of 1mm width and 0.6 mm thickness. Micro-tensile bond strength
      was determined using a mini tensile testing machine (COMPACT Gauge, DILLON).
      RESULTS: Mean values of MTBS were: 31.2 MPa (SD14.5) for surface enamel and 47.9
      (SD15.0) for subsurface enamel. SIGNIFICANCE: There was a significant difference
      between the two groups P = 0.001. It was concluded that subsurface enamel has
      significantly higher bond strength than surface enamel. This has implications for
      bonding in restorative dentistry and orthodontics.

PMID- 16434094
TI  - Variability of metal contents in the sea rush Juncus maritimus-estuarine sediment
      system through one year of plant's life.
AB  - Metal accumulation by Juncus maritimus and the effect this plant might have on
      the physico-chemical composition of sediments, from Douro river estuary (NW
      Portugal), were investigated through one year of plant's life. The contents of
      Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined (by atomic absorption
      spectrophotometry) in sediments, rhizosediments (those among plant roots and
      rhizomes) and different tissues of J. maritimus. Two estuarine sites with
      different characteristics were studied, one a sandy sediment with relatively low
      organic matter content, the other a muddy site. The role of the plant seemed to
      be markedly dependent on the sediment composition. At the sandy site, significant
      variations throughout the year (a decrease from winter to summer and an increase
      in autumn) either in rhizosediment and sediment or in J. maritimus roots were
      only observed in Cd and Cu levels. These variations were the same in both
      compartments, probably caused by tidal water movements and the activity of the
      plant. At the muddy site, variations throughout the year were observed for all
      studied elements but Pb. Changes in the Cd and Zn contents of roots were opposite
      to those in the rhizosediment (uptake of Cd and Zn by J. maritimus roots in
      summer may have caused a decrease in rhizosediment levels). Fe and Mn showed
      similar patterns of variation in both roots and rhizosediment (contents
      significantly increasing in summer). Higher contents of Fe and Mn in roots in
      summer could be related to changes in mass, higher availability of the elements,
      or accumulation at the surface of the root in (hydr)oxides forms. For the
      remaining elements no significant correlations between rhizosediment and roots
      variations were observed, indicating that their uptake and release by roots were
      not based on single exchanges with the sediment. J. maritimus showed capacity to
      accumulate Cu, Zn and particularly Cd, thus appearing to be useful for the
      phytostabilization of these metals.

PMID- 16434096
TI  - Translational proteomics: developing a predictive capacity -- a review.
AB  - Over the past decade, proteomics has undergone a rapid development and radiation,
      diversifying across the biochemical landscape. While no single technique yet
      delivers complete proteomic coverage, application-specific adaptations afford
      significant opportunity for discovery and the development of predictive capacity
      (e.g. surrogate biomarker and clinical diagnostics). Targeted proteomic
      approaches, protein profiling strategies using affinity capture mass spectrometry
      and solution array represent realistic opportunities to deliver predictive
      capacity. The aim of this review is to provide an overview of proteomic
      technologies and how the outcomes delivered by such platforms may be translated
      into applications of predictive utility in clinical and basic science. In
      particular, recent applications in protein/peptide profiling (solid-phase
      affinity capture mass spectrometry and the targeted approach of antibody arrays)
      and the opportunities they afford researchers within the discipline of
      reproductive biology to develop new diagnostic and prognostic tests and surrogate
      biomarkers to improve the delivery of women's health care are considered.

PMID- 16434095
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone regulation of the
      release of phospholipid metabolites, inflammatory cytokines and proteases from
      human gestational tissues.
AB  - Phospholipid-derived mediators, inflammatory cytokines and extracellular matrix
      remodelling enzymes are all involved in the initiation of human labour and
      delivery. We have previously demonstrated that natural and synthetic PPAR-gamma
      ligands regulate LPS-stimulated pro-inflammatory cytokine release from human
      gestational tissues, however, the effect of these ligands on the basal and/or LPS
      induced expression of prostaglandins and proteases is not known. Therefore, the
      aim of this study was to determine the effects of 15d-PGJ(2) and troglitazone on
      the expression of basal and LPS-stimulated inflammatory mediators in human
      gestational tissues. Human placenta, amnion and choriodecidua (n=5) were
      incubated in the presence or absence of 15 microM 15d-PGJ(2) and 30 microM
      troglitazone under basal and LPS-stimulated (10 microg/ml) conditions. Treatment
      of placenta, amnion and choriodecidua with both 15d-PGJ(2) and troglitazone
      decreased basal and LPS-stimulated IL-1beta, IL-6, IL-10 and TNF-alpha release.
      Basal type II PLA(2) release from placental tissues was also significantly
      decreased by 15d-PGJ(2) and troglitazone. There was no effects of 15d-PGJ(2) and
      troglitazone on cPLA(2) protein expression. Both 15d-PGJ(2) and troglitazone
      significantly decreased basal and LPS-stimulated PGE(2) and PGF(2alpha) release
      from placenta and amnion. However, in choriodecidua, although 15d-PGJ(2)
      decreased basal and/or LPS-stimulated PGE(2) and PGF(2alpha) release, there was
      an increase in PGE(2) and PGF(2alpha) release in the presence of troglitazone.
      15d-PGJ(2) and troglitazone inhibited MMP-9 release from human amnion. NF-kappaB
      DNA binding activity and NF-kappaB p65 protein expression was inhibited by
      treatment with 15d-PGJ(2) in human amnion. There was no effect of 15d-PGJ(2) or
      troglitazone on PPAR-gamma protein, and GW9662 failed to alleviate 15d-PGJ(2) and
      troglitazone inhibition of IL-6 and TNF-alpha release in placenta, amnion and
      choriodecidua. The data demonstrated in this study suggest that the 15d-PGJ(2)
      and troglitazone exhibit anti-inflammatory properties in human gestational
      tissues via PPAR-gamma independent actions.

PMID- 16434097
TI  - Mechanism by which Bombyx mori hemocytes recognize microorganisms: direct and
      indirect recognition systems for PAMPs.
AB  - Hemocytes play an important role in cellular reactions in the immune system.
      Although the recognition of pathogens is thought to involve pattern-recognition
      proteins (PRPs) in insects, the exact mechanisms by which insect hemocytes
      recognize pathogens are not clear. This study examined the mechanism by which
      Bombyx mori hemocytes recognize microorganisms and pathogen-associated molecular
      patterns (PAMPs) using flow cytometry and fluorescence microscopy. Fluorescence
      labeled bacterial or fungal cells were observed to bind to hemocytes and this
      binding was inhibited by adding lipoteichoic acid (LTA) or beta-1,3-glucan.
      Lipopolysaccharide (LPS) bound to hemocytes directly. These results suggest that
      hemocytes have a mechanism that recognizes LPS, LTA, and beta-1,3-glucan
      directly. Previously, we identified two types of C-type lectin (BmLBP and BmMBP)
      and showed that they recognize a variety of PAMPs leading to the induction of
      nodule formation. These lectins enhanced hemocyte binding to microorganisms and
      their direct binding to hemocytes suggests that hemocytes have a mechanism for
      recognizing microorganisms using lectin receptors.

PMID- 16434098
TI  - Community mercury levels in the vicinity of peri-urban waste disposal sites and
      fossil fuel burning operations.
AB  - INTRODUCTION: A study was conducted as a result of concern about mercury
      absorption amongst residents of a peri-urban area in Cape Town, South Africa, in
      close proximity to waste disposal sites and an industrial area. STUDY METHODS:
      The study compared urine mercury concentrations in a random sample of adult
      residents and children in both the formal and informal housing settlements of the
      "exposure" area (n = 90) and a control area (n = 90). A short questionnaire
      elicited demographic, lifestyle and medical details and possible occupational,
      household and environmental mercury exposures. RESULTS: The two samples were
      comparable with respect to background and potential confounding variables. The
      prevalence of urinary mercury levels>or=the WHO reference range in the exposure
      area was also higher than that in the control area (13% vs. 0%). The median
      urinary mercury concentrations in both study areas were below the World Health
      Organisation (WHO) reference level of 5.0 microg/g creatinine. The median level
      in the exposure area was slightly, but statistically significantly, higher than
      in the control area (1.1 vs. 0.25 microg/g creatinine), and the excess persisted
      after controlling for known possible mercury exposures. CONCLUSIONS: This is to
      our knowledge the first study of community inorganic mercury absorption in a
      developing country setting, and where airborne mercury was the exposure of
      concern. It was concluded that the health risk associated with the urinary
      mercury levels of residents in the exposure area was very low. However, low level
      environmental exposure in the area of concern could not be excluded.

PMID- 16434100
TI  - Structure and mechanism in the bacterial dihaem cytochrome c peroxidases.
AB  - The bacterial cytochrome c peroxidases contain an electron-transferring haem c
      (E) and a peroxidatic haem c (P). Many are isolated in an inactive oxidised
      state. Reduction of the E haem promotes Ca(2+)-dependent spin state and
      coordination changes at the P haem rendering it accessible to ligand. Recent
      crystallographic work on the oxidised and mixed valence enzymes has suggested a
      mechanism by which an electron entering the E haem remotely triggers this
      activation of the P haem. Binding of hydrogen peroxide at the activated P haem
      leads to an intermediate catalytic form containing two oxidising equivalents, one
      of which is a ferryl oxene. This form of the enzyme is then reduced by two single
      electron transfers to the E haem delivered by small redox proteins such as
      cytochromes or cupredoxins. The binding of these small redox proteins is
      dominated by global electrostatic forces but the interfaces of the electron
      transfer complexes that are formed are largely hydrophobic and relatively non
      specific. These features allow very high electron transfer rates in the steady
      state.

PMID- 16434099
TI  - Ricin induces IL-8 secretion from human monocyte/macrophages by activating the
      p38 MAP kinase pathway.
AB  - Polymorphonuclear cell (PMN) infiltration is a hallmark of ricin-induced mucosal
      inflammation, yet the cellular processes involved in initiating this reaction
      remain undefined. In this study we report that ricin stimulates the human
      monocyte/macrophages cell line 28SC to secrete IL-8, a potent PMN
      chemoattractant. IL-8 release in response to ricin was both dose- and time
      dependent. 28SC cells did not secrete IL-8 when exposed to formaldehyde
      inactivated holotoxin or ricin B subunit. Furthermore, IL-8 induction could be
      blocked by brefeldin A, which inhibits ricin translocation into the cytosol. As
      predicted from the literature, we observed elevated levels of p38 mitogen
      activated protein kinase (MAPK), a post-transcriptional regulator of IL-8, in
      28SC cells as early as 3h after ricin exposure. Treatment of 28SC cells with the
      pyridylimidizole analogue SB203580, a known inhibitor of p38 MAPK, suppressed
      ricin-mediated IL-8 release. We conclude that ricin stimulates human
      monocyte/macrophages to produce IL-8 by activation of the p38 MAPK pathway,
      raising the possibility that p38 MAPK inhibitors may potentially serve as
      therapeutic agents to suppress mucosal inflammation associated with ricin
      intoxication.

PMID- 16434102
TI  - Are blood cultures necessary in the management of women with complicated
      pyelonephritis?
AB  - OBJECTIVES: Data from previous studies suggest that blood cultures in women with
      uncomplicated acute pyelonephritis (APN) are of limited value. Our objective was
      to assess the role of blood cultures in the management of complicated APN in
      women, and to examine the demographic and clinical characteristics, and the
      outcome as related to the bacteremic status of these patients. METHODS: Data from
      medical records of 158 women hospitalized with complicated APN over a 2-year
      period were analyzed retrospectively. It included demographic, clinical and
      laboratory data, details of the empiric antimicrobial therapy, urine and blood
      culture results, complications and clinical outcome. RESULTS: Out of 158 women
      with complicated APN, in 155 (98%) pathogens grew in the urine culture, and 33
      (20.9%) of them had bacteremia. In the great majority of patients (98.7%), the
      blood cultures were sterile, or contained the same phenotypically profiled
      pathogen that was isolated from the urine. Only in two patients (1.3%), the blood
      cultures grew pathogens different from those found in the urine. The initial
      empiric antimicrobial therapy was not changed in any of the patients. No
      significant difference existed between the bacteremic and nonbacteremic patients
      in the demographic and clinical characteristics, the severity of disease or the
      outcome. CONCLUSION: In the management of complicated APN, routine cultures of
      blood should be reevaluated.

PMID- 16434101
TI  - Bacterial profile and clinical outcome of childhood meningitis in rural Yemen: a
      2-year hospital-based study.
AB  - BACKGROUND: Childhood acute bacterial meningitis (ABM) is an important cause of
      death and long-term neurological disability in Yemen, the only low income-high
      mortality country in the Arabian Peninsula. The objective of this study was to
      document the microbial characteristics, the antibacterial sensitivity pattern,
      and the outcome for children hospitalized with ABM, prior to the introduction of
      Haemophilus influenzae type b (Hib) vaccine in Yemen. PATIENTS AND METHODS: The
      study was retrospective, conducted at a rural district hospital, serving the
      rural population of the northern parts of Yemen. All patients aged 1 month-15
      years admitted between May 1999 and June 2001, with clinical evidence of
      meningitis and cerebrospinal fluid (CSF) cultured, were included in the study.
      Clinical information from case notes, including CSF result and the outcome on
      discharge, were obtained. Analysis of extracted data was performed using Epi Info
      software. RESULTS: During the 2-year study period, 160 study patients met the
      inclusion criteria, and 7 (4.4%) were negative for bacterial growth. In the 153
      positive cultures there were 46 (30.1%) Streptococcus pneumoniae (SP), 23 (15%)
      H. influenzae (HI), 81 (52.9) Neisseria meningitidis (NM), 2 (1.3%)
      Staphylococcus aureus (S. aureus), and 1 (0.7%) Escherichia coli. Sixteen study
      patients died (overall case fatality rate (CFR) 10%), 7 aged under 12 months, 6
      aged 12-60 months, and 3 more than 60 months. Ten deaths were due to SP
      meningitis, 2 HI meningitis, 3 NM meningitis, and 1 had S. aureus. Of the 144
      survivors, 28 (19.4%) developed permanent neurological complications, 17 aged
      less than 12 months, 6 aged 12-60 months, and 5 more than 60 months. SP
      meningitis accounted for 57.1% (16/28), and 6 (21.4%) had HI meningitis. Among
      the 89 aged 1-60 months, 13 died (CFR 14.6%), and 23 (30.3%) of the 76 survivors
      developed permanent complications. Of those tested 20% and 35% of the 20 HI
      tested isolates and 9.5% and 14.3% of the 42 SP isolates, were resistant to
      ampicillin and penicillin G, respectively, and the majority of the 81 NM isolates
      were sensitive to both. The 3 pathogens were largely resistant to gentamicin, and
      almost all were susceptible to chloramphenicol and cefotaxime. CONCLUSION: In
      contrast to the studies from the low-mortality countries of the region, our study
      showed that the predominant pathogens of childhood ABM were SP and NM. SP
      meningitis was associated with increased mortality and permanent disability.

PMID- 16434103
TI  - The usefulness of magnetic resonance imaging (MRI) for disseminated
      trichosporosis of the gastrocnemius muscles.
AB  - A 30-year-old man with acute myeloid leukemia who was pancytopenic after
      undergoing intensive chemotherapy developed pyrexia and severe pain of both lower
      legs. We immediately started empiric therapy with cefepime, vancomycin, and
      fluconazole for febrile neutropenia. However, symptoms progressed. After 4 days,
      Trichosporon was isolated from venous blood cultures. MRI showed hyperintense
      lesions within both gastrocnemius muscles and demonstrated reactive
      vasodilatation and interstitial tissue edema, thought to be induced by
      hyperpermeability of vessel membranes due to the local fungal infection.
      Amphotericin B was very effective against this organism. Trichosporosis is a rare
      infectious disease generally occurring in immunocompromized hosts. To the best of
      our knowledge, this is first reported case of bilateral Trichosporon infection of
      lower leg muscles. Severe leg pain was one of the most important signs of fungal
      infection in this patient with hematologic malignancy.

PMID- 16434104
TI  - The role of the phosphatidylinositide 3-kinase-protein kinase B pathway in
      schizophrenia.
AB  - Neuroanatomical studies of brains from schizophrenic patients report evidence for
      neuronal dystrophy, while in genetic studies in schizophrenia there is evidence
      for mutations in growth factors and the downstream enzymes phosphatidylinositide
      3-kinase (PI3K) and protein kinase B (PKB). Since the PI3K-PKB pathway is
      involved in cellular growth and proliferation, reduced activity of this cascade
      in schizophrenia could at least partly explain the neuronal dystrophy. Risk
      factors for schizophrenia, such as corticosteroids and cannabis, suppress the
      activity of the PI3K-PKB pathway. Conversely, estrogen and vitamin D, 2 factors
      with a moderate protective activity in schizophrenia, electroconvulsive shock
      therapy, and chronic treatment with antipsychotic compounds stimulate the
      pathway. Reduced activity of the PI3K-PKB pathway makes the brain more
      susceptible to virus infections, anoxia, and obstetric complications (recognized
      risk factors for schizophrenia), whereas a diminution of growth factor levels
      towards the end of puberty could contribute to an increase in schizophrenia
      symptoms observed around that time. On the other hand, constitutive
      (over)activation of the PI3K-PKB pathway increases cancer risk. Consequently, the
      presumed hypoactivity of the PI3K-PKB cascade might provide a partial explanation
      for the remarkable epidemiological finding of a reduced cancer rate in
      schizophrenic patients. Recognition of the role of a dysfunctional PI3K-PKB
      pathway in schizophrenia might help in the discovery of hitherto undetected
      causative gene mutations and could also lead to novel therapeutic approaches.
      However, a major challenge that remains to be solved is how the PI3K-PKB pathway
      can be activated without increasing the risk of cancer.

PMID- 16434105
TI  - Design of a torque-controlled manipulator to analyse the admittance of the wrist
      joint.
AB  - This paper describes the design of a torque-controlled manipulator to identify
      the dynamics of the wrist joint. With torque disturbances, the subject can
      actively control the joint angle, giving a natural task. The application of a
      hybrid haptic controller guarantees linearity over a large bandwidth and
      adjustable virtual dynamics. The haptic controller has a bandwidth of 50 Hz,
      meaning that the virtual dynamics are realistically felt at up to 50 Hz. To let
      the subject 'feel' the torque, disturbances as well as possible the apparent, or
      virtual, dynamics of the device must be small. The minimal apparent inertia of
      the device is 1.6 g m(2), which is of the same order as for a normal wrist, and
      the minimal damping and stiffness are negligible. To judge the accuracy of the
      manipulator, loads of known physical properties were attached and their
      parameters were quantified. The parameters of the loads were estimated with a
      maximum error of 5%. As the eigenfrequency of a (co)-contracted human wrist is
      approximately 15 Hz, the 50-Hz bandwidth of the haptic device is sufficient to
      measure all relevant dynamics of the human wrist. With this device, the dynamics
      of the human wrist joint can be measured under varying virtual dynamics, as well
      as the effect of neurological dysfunction on human motor control, for example.

PMID- 16434106
TI  - Time-frequency analysis of spike-wave discharges using a modified wavelet
      transform.
AB  - The continuous Morlet wavelet transform was used for the analysis of the time
      frequency pattern of spike-wave discharges (SWD) as can be recorded in a genetic
      animal model of absence epilepsy (rats of the WAG/Rij strain). We developed a new
      wavelet transform that allows to obtain the time-frequency dynamics of the
      dominating rhythm during the discharges. SWD were analyzed pre- and post
      administration of certain drugs. SWD recorded predrug demonstrate quite uniform
      time-frequency dynamics of the dominant rhythm. The beginning of the discharge
      has a short period with the highest frequency value (up to 15 Hz). Then the
      frequency decreases to 7-9 Hz and frequency modulation occurs during the
      discharge in this range with a period of 0.5-0.7 s. Specific changes of SWD time
      frequency dynamics were found after the administration of psychoactive drugs,
      addressing different brain mediator and modulator systems. Short multiple SWDs
      appeared under low (0.5 mg/kg) doses of haloperidol, they are characterized by a
      fast frequency decrease to 5-6 Hz at the end of every discharge. The frequency of
      the dominant frequency of SWD was not stable in long lasting SWD after 1.0 mg/kg
      or more haloperidol: then two periodicities were found. Long lasting SWD seen
      after the administration of vigabatrin showed a stable frequency of the
      discharge. The EEG after Ketamin showed a distinct 5 s quasiperiodicity. No clear
      changes of time-frequency dynamics of SWD were found after perilamine. It can be
      concluded that the use of the modified Morlet wavelet transform allows to
      describe significant parameters of the dynamics in the time-frequency domain of
      the dominant rhythm of SWD that were not previously detected.

PMID- 16434107
TI  - Suicide attempts amongst elderly bipolar patients.
AB  - BACKGROUND: Bipolar disorder is associated with high risk of suicide. In the
      elderly suicide rates are the highest of all age groups. There is a paucity of
      data regarding suicide amongst elderly bipolar patients. Mood stabilizers and
      particularly lithium are established as "antisuicide" compounds. OBJECTIVE: We
      aimed to evaluate the association between exposure to psychotropic drugs and
      suicide attempts in a cohort of elderly patients suffering from bipolar affective
      disorder (BAD). METHOD: This was a preliminary, retrospective, matched, case
      controlled evaluation over a 10-year period. All records of admissions of
      patients with BAD (ICD-10) were assessed. The index group comprised all patients
      who had attempted suicide in the month prior to admission. The control group
      consisted of the next admission of a patient suffering from BAD, matched for sex
      and age who had not attempted suicide in the month prior to admission. RESULTS:
      The index group during the period 1995 to 2004 consisted of 16 patients, (8 men
      and 8 women.), mean age 74.8 +/- 1.3 years. The control group patients (N = 16)
      were matched for age (mean 74.3 +/- 1.5 years) and sex. The number of patients
      who had a history of a suicide attempt was significantly greater in the index
      group (7/16 vs., 2/16; p = 0.039). In the control group patients treated by both
      a mood stabilizer and an antidepressant were at a significantly lower risk for
      recent suicide attempt (p = 0.047). LIMITATIONS: Sample size is small, treatments
      were not standardized and data were collected retrospectively. CONCLUSION:
      Elderly BAD patients treated with mood stabilizers and antidepressants may be at
      reduced risk of attempting suicide. These findings need support from prospective
      randomized trials.

PMID- 16434108
TI  - Sexual pleasure in women with obsessive-compulsive disorder?
AB  - BACKGROUND: Although patients with OCD have reported sexual dissatisfaction
      frequently, controlled studies are sparse. This study compared subjective
      appreciation of sexuality and sexual functioning between OCD patients and healthy
      subjects and controlled for the influence of medication or OCD subtypes on sexual
      functioning and satisfaction. METHODS: Self-report questionnaires were sent to
      350 female outpatients with OCD and 101 questionnaires were completed. RESULTS:
      OCD patients reported significantly more sexual disgust (t = 4.48, p < 0.001),
      less sexual desire (t = 5.52, p < 0.001), sexual arousal (t = 4.28, p < 0.001),
      and satisfying orgasms (t = 4.94, p < 0.001), than controls. Neither medication
      nor OCD phenotypes did affect outcome. LIMITATIONS: A self-report questionnaire
      and relatively low response-rate (29%) could have biased the results and the
      sample was limited to women so results might not be generalisable to men.
      CONCLUSIONS: Female patients with OCD report low sexual pleasure, high sexual
      disgust and diminished sexual functioning, which are not only attributed to
      medication or contamination obsessions. In the future, clinicians should
      explicitly ask for sexual function in the assessment of patients with OCD.

PMID- 16434109
TI  - A multiplex RT-PCR method for screening of reassortant live influenza vaccine
      virus strains.
AB  - A system based on reverse transcription polymerase chain reaction (RT-PCR) of the
      RNA genome was established to identify genetic composition of influenza viruses
      generated by reassortment between an attenuated donor virus and virulent wild
      type virus. The primers were designed, by multiple sequence alignment of variable
      regions, specific for cold-adapted donor virus HTCA-A 101, as compared to other
      influenza A viruses. The specificity of each primer set was confirmed and the
      primers were combined to perform RT-PCR in multiplex manner. The multiplex PCR
      was adopted to distinguish the 6:2 reassortant viruses containing six internal
      genome segments of attenuated donor virus and two surface antigens of virulent
      strain from the wild type viruses. The method allowed us to optimize the
      reassorting process on a routine basis and to confirm the selection of
      reassortant clones efficiently. The method is suitable for analyzing the
      contribution of specific gene segments for growth and attenuating characteristics
      and for generation of live attenuated vaccine by annual reassortment.

PMID- 16434110
TI  - Food selection, growth and physiology in relation to dietary sodium chloride
      content in rainbow trout (Oncorhynchus mykiss) under chronic waterborne Cu
      exposure.
AB  - Waterborne Cu is toxic to Na(+) and Cl(-) regulation in freshwater fish, and Cu
      is taken up, at least in part, via the Na(+)-transport pathway in the gills.
      Therefore, we hypothesized that freshwater fish may mitigate the toxic effects of
      waterborne Cu by selecting a NaCl-enriched diet over a normal diet. We tested
      this hypothesis in juvenile rainbow trout (Oncorhynchus mykiss) by offering them
      the choice between NaCl-enriched (1.9 mmol g(-1)Na(+)) and normal (0.2 mmol g(
      1)Na(+)) diets under a chronic waterborne Cu exposure of 55 microg L(-1) for a
      period of 28 days. Contrary to expectation, trout exhibited a preference for NaCl
      enriched diet under control conditions, while exposure to chronic waterborne Cu
      severely disrupted their normal feeding pattern with an accompanying loss of
      preference for the NaCl-enriched diet. Waterborne Cu exposure also severely
      affected appetite and growth. Both appetite and growth gradually recovered with
      time, but remained significantly impaired relative to Cu-unexposed fish until the
      end of the exposure. Waterborne Cu exposure also significantly increased Cu
      accumulations in target organs (gill, liver, and gut), plasma and whole body.
      However, Cu accumulation decreased substantially towards the end of the exposure
      in target organs and whole body as well as in plasma in Cu-exposed fish with
      dietary choice relative to Cu-exposed fish with normal diet. These adjustments
      were concurrent with the gradual recovery of appetite, which also led to
      increased ingestion of the NaCl-enriched diet. Interestingly, this elevated
      dietary uptake of NaCl produced significant stimulation of Na(+) efflux in Cu
      exposed fish. Subsequently, it also led to significant elevation of Na(+) levels
      in target organs and whole body, and restored the decrease of plasma Na(+) and
      Cl(-) levels in Cu-exposed fish. The NaCl supplemented diet appeared to be
      beneficial in compensating Na(+) and Cl(-) losses from the body induced by
      waterborne Cu. Overall, these results demonstrate that a NaCl-enriched diet,
      although consumed in relatively reduced quantities due to the impairment of food
      selection and appetite, can help to protect freshwater fish against chronic
      waterborne Cu toxicity.

PMID- 16434112
TI  - Characterization of a mutation and an alternative splicing of UDP-galactose
      transporter in MDCK-RCAr cell line.
AB  - The UDP-galactose (UDP-Gal) transporter present in the Golgi apparatus is a
      member of a transporter family comprising hydrophobic proteins with multiple
      transmembrane domains. Co-immunoprecipitation experiments showed that the full
      length UDP-Gal transporter protein forms oligomeric structures in the MDCK cell.
      A ricin-resistant mutant of the MDCK cell line (MDCK-RCA(r)) is deficient in
      galactose linked to macromolecules because of a lower UDP-Gal transport rate into
      the Golgi apparatus. We cloned this mutated protein and found that it contains a
      stop codon close to the 5' terminus of its open reading frame. We also detected a
      shorter splicing variant of the UDP-Gal transporter which contains a 183-nt in
      frame deletion in both the wild-type and the mutant mRNA. We showed that the
      protein, when overexpressed, is localized in the Golgi apparatus and could
      partially correct the phenotype of the MDCK-RCA(r) and CHO-Lec8 mutant cell
      lines. The level of mRNA of the UDP-Gal transporter is much lower (25-30 copies
      per cell) than those of the CMP-sialic acid transporter (100 copies per cell),
      UDP-N-acetylglucosamine transporter (80 copies per cell), and GDP-fucose
      transporter (65 copies per cell). The transcript level of the shorter splicing
      variant of the UDP-Gal transporter is extremely rare in wild-type MDCK cells (a
      few copies per cell), but it is significantly increased in the mutant, RCA
      resistant cells.

PMID- 16434111
TI  - A member of the transforming growth factor-beta receptor family from Echinococcus
      multilocularis is activated by human bone morphogenetic protein 2.

PMID- 16434113
TI  - Recovery and outcome of delirium in elderly medical inpatients.
AB  - This study investigates the relationships between delirium, cognitive impairment
      and acute illness severity with adverse clinical outcomes; in-hospital mortality,
      hospital length of stay, or new entry to a care home. It is a prospective
      observational study of medical inpatients 70 years or older, with repeated
      measurements of cognition, delirium status, delirium severity, and severity of
      physical illness every 3 days until the 18th day and then the 28th day of
      hospitalization. Of 94 participants, 33 had delirium and 14 recovered during
      their hospitalization. Predictor variables for recovery were initial Mini Mental
      State Examination (MMSE) (p=0.003) and severity of delirium at second assessment
      (p=0.02), for mortality initial MMSE (p=0.002) and for discharge to care home
      were initial delirium status (p=0.008) and age (p=0.004). Delirious people newly
      discharged to care homes stayed longer in hospital than those discharged to their
      previous address (p=0.016). We conclude that delirium is not a transient
      disorder. The presence of delirium was not related to measures of the severity of
      physical illness or disability. High mortality was associated with delirium but
      was specifically associated with cognitive impairment. Prolonged length of stay
      of delirious people may depend on discharge destination.

PMID- 16434114
TI  - Assessment of coronary plaque collagen with polarization sensitive optical
      coherence tomography (PS-OCT).
AB  - INTRODUCTION: Current evidence indicates that most plaques classified as
      vulnerable or ruptured plaque do not lead to unstable angina or myocardial
      infarction. Improved methods are needed to risk stratify plaques to identify
      those which lead to most acute coronary syndromes. Collagen depletion in the
      intima overlying lipid collections appears to be a critical component of unstable
      plaques. In this study, we use polarization sensitive optical coherence
      tomography (PS-OCT) for the assessment of coronary plaque collagen. Collagen is
      birefringent, meaning that different polarization states travel through it at
      different velocities. METHODS AND RESULTS: Changes in PS-OCT images are a measure
      of tissue birefringence. Twenty-two coronary artery segments were imaged with PS
      OCT and analyzed by picrosirius staining (a measure of collagen intensity and
      fiber size) and trichrome blue. The regression plot between PS-OCT changes and
      measured collagen yielded a correlation coefficient value of 0.475 (p<0.002). The
      predictive value of a PS-OCT measurement of negligible birefringence (less than
      33% change) for minimal collagen was 93% while the predictive value of high
      birefringence (greater than 66% change) for high collagen concentrations was 89%.
      The effect of fiber type (chemical composition) was minimal relative to the
      effect due to fiber concentration. CONCLUSION: The capability of PS-OCT to assess
      plaque collagen content, in addition to its ability to generate high resolution
      structural assessments, make it a potentially powerful technology for identifying
      high risk plaques.

PMID- 16434115
TI  - Improved purification of Piscirickettsia salmonis using Percoll gradients.
AB  - Viable preparations of intact Piscirickettsia salmonis, purified from host cell
      material, are necessary for studying characteristics associated with this
      bacterium. However, purification of the organism is difficult due to its obligate
      intracellular nature. A simple and effective method for isolating whole P.
      salmonis, which is quick and easy to perform, but still maintains the viability
      and antigenicity of the bacterium is described. P. salmonis was purified by
      differential pelleting and density gradient centrifugation using 30%, 40%, or 50%
      (v/v) Percoll gradients. Following fractionation, a band with a density of 1.056
      1.080 was found to be composed entirely of rickettsiae, confirmed by fluorescent
      antibody technique (IFAT). Purity of the P. salmonis from different stages of the
      purification process was assessed by light and transmission electron microscopy,
      and the viability of yields determined from a plaque assay and a tissue culture
      infective dose (TCID(50) ml(-1)). P. salmonis recovered from the 30% Percoll
      gradient appeared to retain their intracellular structure better than P. salmonis
      obtained from the 40% and 50% Percoll gradients, and appeared to have a greater
      viability. Differences were seen between P. salmonis-infected CHSE-214 cells and
      purified P. salmonis when compared by SDS-PAGE and Western blotting, and less
      host cell contamination was present in preparations obtained from the 30% Percoll
      gradient. Finally ten different P. salmonis isolates obtained from three
      different geographical locations and four different fish species, were purified
      using the 30% Percoll gradient. When the morphology of these was compared by
      transmission electron microscopy (TEM), they appeared similar in size and
      appearance, although isolate R980769 was highly pleomorphic and isolate R-29 was
      larger than the other isolates examined.

PMID- 16434117
TI  - Cultivating conditions influence exopolysaccharide production by the edible
      Basidiomycete Antrodia cinnamomea in submerged culture.
AB  - Antrodia cinnamomea is a medicinal fungus that has been used in Taiwan as a
      traditional medicine for the treatment of tumorigenic diseases. We prove that
      controlling the culturing conditions (i.e., temperature and pH) and modifying the
      composition of the medium (i.e., carbon, nitrogen, mineral sources and vitamins)
      can dramatically enhance the production of the exopolysaccharide of A.
      cinnamomea. We have found that the temperature, initial pH, and agitation time
      are all critical for exopolysaccharide production during the cultivation of A.
      cinnamomea in submerged cultures; our optimized conditions were 28 degrees C, pH
      5.5, and 14 days, respectively. In addition, when optimizing the effects of
      additional nutrition, we found that 5% (v/v) glucose, 0.5% (v/v) calcium nitrate,
      0.1% (v/v) ferrous sulfate, and 0.1% (v/v) nicotinic acid led to the greatest
      production of exopolysaccharides; the exopolysaccharide production, mycelial
      biomass and specific product yield reached 0.49 g/l, 2.60 g/l and 0.19 g/g,
      respectively. The results indicate that nutrients can be utilized to improve the
      production of exopolysaccharide and that good mycelial growth does not seem to be
      a determining factor for a high production yield of exopolysaccharide in A.
      cinnamomea.

PMID- 16434118
TI  - Moulds, yeasts and aerobic plate counts in ginseng supplements.
AB  - Forty six ginseng supplement samples including Siberian ginseng root, Chinese
      ginseng herb and root, and American ginseng root and extract were purchased from
      retail in the Washington, DC area and from Penn Herb Co. (Philadelphia, PA) and
      tested for mould and yeast (MY) contamination and the presence of aerobic
      mesophilic bacteria (APC). Results indicated that 100% of the Siberian ginseng
      samples were contaminated with fungi and bacteria. MY counts ranged from 8.0 x
      10(2) to 1.4 x 10(3) cfu/g whereas the APCs were between 2.3 x 10(4) and 1.0 x
      10(6) cfu/g. Most common fungi encountered in this commodity were Penicillium
      spp., Eurotium rubrum, E. chevalieri and Rhizopus spp. Seventy-eight percent of
      the Chinese ginseng herb samples were contaminated with fungi and 89% with
      bacteria at levels ranging between <100 and 6.0 x 10(4) and <100 and 1.2 x 10(6)
      cfu/g, respectively. Moulds commonly isolated were Alternaria alternata,
      Aspergillus niger, Aspergillus spp., Cladosporium spp., E. chevalieri,
      Penicillium spp. and Rhizopus spp. Fifty six percent of the Chinese ginseng root
      samples tested contained fungi (A. niger, Rhizopus spp. and yeasts), and 100%
      contained bacteria. Fungal counts ranged between <100 and 1.4 x 10(3) cfu/g and
      APCs were between 3.0 x 10(2) and 6.8 x 10(5) cfu/g. Forty-eight percent of the
      American ginseng root samples contained moulds and 30% showed bacterial
      contamination. MY counts were between <100 and 4.3 x 10(5) cfu/g whereas APCs
      were between <100 and 4.5 x 10(4) cfu/g. A. flavus was isolated from 9% and
      Penicillium spp. were recovered from 39% of the tested samples. This is the first
      report of A. flavus contamination in ginseng supplements. No moulds or yeasts
      were found in ginseng extract, but 50% of these samples contained bacteria at
      levels ranging between <100 and 1.0 x 10(3) cfu/g.

PMID- 16434116
TI  - Cortisol secretion patterns in addiction and addiction risk.
AB  - Addiction to alcohol or nicotine involves altered functioning of the brain's
      motivational systems. Altered functioning of the hypothalamic-pituitary
      adrenocortical (HPA) axis may hold clues to the nature of the motivational
      changes accompanying addiction and vulnerability to addiction. Alcohol and
      nicotine show at least three forms of interaction with HPA functioning. Acute
      intake of both substances causes stress-like cortisol responses. Their persistent
      use may dysregulate the HPA. Finally, the risk for dependence and for relapse
      after quitting may be associated with deficient cortisol reactivity to a variety
      of stressors. The HPA is regulated at the hypothalamus by diurnal and metabolic
      signals, but during acute emotional states, its regulation is superseded by
      signals from the limbic system and prefrontal cortex. This top-down organization
      makes the HPA responsive to inputs that reflect motivational processes. The HPA
      is accordingly a useful system for studying psychophysiological reactivity in
      persons who may vary in cognitive, emotional, and behavioral tendencies
      associated with addiction and risk for addiction. Chronic, heavy intake of
      alcohol and nicotine may cause modifications in these frontal-limbic interactions
      and may account for HPA response differences in seen in alcoholics and smokers.
      In addition, preexisting alterations in frontal-limbic interactions with the HPA
      may reflect addiction-proneness, as shown in studies of offspring of alcohol- and
      drug-abusing parents. Continuing research on the relationship between HPA
      function, stress responsivity, and the addictions may yield insights into how the
      brain's motivational systems support addictions and risk for addictions.

PMID- 16434119
TI  - Current challenges and developments in GC-MS based metabolite profiling
      technology.
AB  - Gas chromatography-mass spectrometry (GC-MS) based metabolite profiling of
      biological samples is one of the key technologies for metabolite profiling and
      substantially contributes to our understanding of the metabolome. While the
      technology is in increasing use it is challenged with novel demands. Increasing
      the number of metabolite identifications within existing profiling platforms is
      prerequisite for a substantially improved scope of profiling studies. Clear,
      reproducible strategies for metabolite identification and exchange of
      identifications between laboratories will facilitate further developments, such
      as the extension of profiling technologies towards metabolic signals and other
      technically demanding trace compound analysis. Using GC-MS technology as an
      example the concept of mass spectral tags (MSTs) is presented. A mass spectral
      tag is defined by the chemometric properties, molecular mass to charge ratio,
      chromatographic retention index and an induced mass fragmentation pattern such as
      an electron impact mass spectrum (EI-MS) or secondary fragmentation (MS(2)).
      These properties if properly documented will allow identification of hitherto non
      identified MSTs by standard addition experiments of authenticated reference
      substances even years after first MST description. Strategies are discussed for
      MST identification and enhanced MST characterization utilizing experimental
      schemes such as in vivo stable isotope labelling of whole organisms and open
      access information distribution, for example the GMG internet platform initiated
      in 2004 (GMD, http://www.csbdb.mpimp-golm.mpg.de/gmd.html).

PMID- 16434120
TI  - The culture of designing hepato-biliary randomised trials.

PMID- 16434121
TI  - A lichen protected by a super-hydrophobic and breathable structure.
AB  - A species of lichen, Lecanora conizaeoides, is shown to be super-hydrophobic. It
      uses a combination of hydrophobic compounds and multi-layered roughness to shed
      water effectively. This is combined with gas channels to produce a biological
      analogue of a waterproof, breathable garment. The particular lichen grows mostly
      during wet seasons and is unusually resistant to acid rain [Hauck, M., 2003. The
      Bryologist 106(2), 257-269; Honegger, R., 1998. Lichenologist 30(3),193-212]. The
      waterproof, breathable surface allows this lichen to photosynthesise when other
      species are covered with a layer of water. In addition, rainwater runs off the
      surface of the organism, reducing its intake of water from above and probably
      contributing to its resistance to acid rain.

PMID- 16434122
TI  - Ovarian jelly-peptides (OJPs), a new family of regulatory peptides identified in
      the cephalopod Sepia officinalis.
AB  - In marine invertebrates, numerous water-borne peptides involved in reproductive
      behavior have been characterized. In this study, we focused on three ovarian
      water-borne peptides, released by full-grown oocytes (FGO) in the genital coelom
      and in the lumen of the oviduct in the cuttlefish Sepia officinalis. The first
      one (DQVKIVL), was characterized by the monitoring of HPLC purified fraction
      using a myotropic bioassay. Subsequently, a peptidomic approach consisting of a
      mass spectrometry comparative screening performed between the peptide content of
      FGO with that of FGO-conditioned medium, led to the identification of two
      additional water-borne peptides. The second peptide identified (DEVKIVL) was
      characterized by MS/MS and the primary structure of the third one (DEVKIVLD) was
      elucidated by a combination of Edman degradation, acid hydrolysis and MS/MS
      analysis. Sequence homology, tissue mapping and bioactivity demonstrate that
      these peptides belong to the same family. DQVKIVL-related-peptides strictly
      localized in the female genital tract modulate the whole female genital tract and
      the main nidamental gland contractions. Furthermore, these peptides form a jelly,
      when resuspended in water. This particular property could play an important role
      in the kinetics of peptide diffusion in the external medium. Thus, these
      regulatory peptides were named ovarian jelly-peptides (OJPs).

PMID- 16434124
TI  - Neuropsychological and behavioural correlates of CSF biomarkers in dementia.
AB  - To improve clinical, neuropsychological and behavioural characterisation of the
      cerebrospinal fluid (CSF) biomarkers beta-amyloid((1-42)) protein (Abeta42),
      protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across
      diagnostic dementia categories, a prospective study was set up. Patients with
      probable Alzheimer's disease (AD) (n=201), AD with cerebrovascular disease (CVD)
      (AD+CVD) (n=33), frontotemporal dementia (FTD) (n=27), dementia with Lewy bodies
      (DLB) (n=22) and healthy controls (n=148) were included. All patients underwent
      neuropsychological examination and behavioural assessment by means of a battery
      of behavioural assessment scales. CSF was obtained by lumbar puncture and levels
      of Abeta42, tau and P-tau181 were determined with commercially available ELISA
      kits. Negative correlations between CSF Abeta42 levels and aggressiveness
      (Spearman: r=-0.223; p=0.002) and positive correlations with age at inclusion
      (r=0.195; p=0.006), age at onset (r=0.205; p=0.003) and MMSE scores (r=0.198;
      p=0.005) were found in AD. In AD+CVD, CSF Abeta42 levels were correlated with
      MMSE (r=0.482; p=0.006), Hierarchic Dementia Scale (r=0.503; p=0.017) and Boston
      Naming Test (r=0.516; p=0.012) scores. In controls, age was positively correlated
      with CSF tau (r=0.465; p<0.001) and P-tau181 levels (r=0.312; p<0.001). CSF tau
      and P-tau181 levels correlated significantly in all groups, whereas CSF Abeta42
      correlated with tau and P-tau181 levels in healthy controls only. Negative
      correlations between CSF Abeta42 levels and aggressiveness were found in AD
      patients. CSF Abeta42 seems to be a stage marker for AD (+/-CVD) given the
      positive correlations with neuropsychological test results suggesting that CSF
      Abeta42 might be of help for monitoring disease progression. Different
      correlations between age and CSF biomarker levels were obtained in healthy
      controls compared to AD patients, indicating that AD-induced pathophysiological
      processes change age-dependent regulation of CSF biomarker levels.

PMID- 16434123
TI  - The melanocortin system and energy balance.
AB  - The melanocortins, a family of peptides produced from the post-translational
      processing of pro-opiomelanocortin (POMC), regulate ingestive behavior and energy
      expenditure. Loss of function mutations of genes encoding POMC, or of either of
      two melanocortin receptors expressed in the central nervous system (MC3R, MC4R),
      are associated with obesity. The analyses of MC4R knockout mice indicate that
      activation of this receptor is involved in the regulation of appetite, the
      adaptive metabolic response to excess caloric consumption, and negative energy
      balance associated with cachexia induced by cytokines. In contrast, MC3R knockout
      mice exhibit a normal, or even exaggerated, response to signals that induce a
      state of negative energy balance. However, loss of the MC3R also results in an
      increase in adiposity. This article discusses the regulation of energy balance by
      the melanocortins. Published and newly presented data from studies analyzing of
      energy balance of MC3R and MC4R knockout mice indicate that increased adiposity
      observed in both models involves an imbalance in fat intake and oxidation.

PMID- 16434125
TI  - Verbal paired-associate learning by APOE genotype in non-demented older adults:
      fMRI evidence of a right hemispheric compensatory response.
AB  - Previous studies of episodic memory report a greater extent of blood-oxygenation
      level-dependent (BOLD) response in non-demented older adults with the
      apolipoprotein E epsilon-4 (APOE epsilon4) allele than in those without the
      allele. We conducted a functional MRI study to investigate whether APOE genotype
      is related to brain response to verbal paired-associate encoding and
      consolidation, particularly in the right hemisphere, among non-demented older
      adults. Structurally segmented volumes and BOLD response were measured in 13 non
      epsilon4 and 12 epsilon4 subjects. The epsilon4 group displayed greater
      activation than the non-epsilon4 group in multiple right hemisphere regions for
      previously encoded word pairs relative to fixation. Activation within manually
      outlined hippocampal regions of interest also displayed genotype-specific
      dissociations consistent with whole brain analyses. Furthermore, this
      differential BOLD response occurred in the presence of equivalent behavioral and
      neuropsychological performances as well as comparable hippocampal and overall
      structural segmentation volumes between groups. Results implicate a widely
      distributed and interconnected network of right hemisphere brain regions that may
      be involved in compensating for APOE epsilon4-related deficiencies associated
      with verbal episodic memory encoding and consolidation.

PMID- 16434126
TI  - Facilitating undergraduate nurses clinical practicum: the lived experience of
      clinical facilitators.
AB  - Clinical practicum experience for undergraduate nurses remains undisputed as an
      essential component of any program. Exposure to the reality of professional
      practice and its integration of explicit, with tacit knowledge, is invaluable in
      producing skilled clinicians. Currently there are many issues that have arisen
      regarding clinical practice education for undergraduate nurses in Australia
      including; ongoing financial support and resourcing of clinical placements.
      Developing an understanding of these issues is central to the provision of
      quality clinical education. The aim of this study is to reveal dimensions of the
      lived experience of being a clinical facilitator, a popular model of nursing
      clinical education, to come to an understanding of how facilitation actually
      takes place in the clinical environment. The Hermeneutic phenomenological
      approach used in this study has brought to light five essential themes that
      elucidate the phenomena of facilitation. Those themes have been identified as;
      knowing your own limitations, employing the notion of stepping in or stepping
      back, developing alliances, acknowledging the reciprocity of the learning
      experience, and identifying appropriate clinical buddies. The recommendations
      from this study will have an impact on current issues and will inturn, influence
      the quality of clinical education for all stakeholders.

PMID- 16434127
TI  - A clinical trial of prime-boost immunisation with the candidate malaria vaccines
      RTS,S/AS02A and MVA-CS.
AB  - Heterologous prime-boost immunisation with RTS,S/AS02A and the poxvirus MVA-CS
      was evaluated in 18 healthy malaria-naive subjects in Oxford. Both priming with
      RTS,S and boosting MVA-CS, and the reverse, were found to be safe and well
      tolerated. T cell responses as measured by IFN-gamma ex vivo ELISPOT were
      induced, but the responses were low to moderate in both groups, with heterologous
      boosting yielding only small increments in T cell immunogenicity and no increased
      antibody response. Protection against 3D7 Plasmodium falciparum sporozoite
      challenge 4 weeks after the final vaccination was equal for both regimens at 33%
      (95% C.I. 4.3-77.7%), with one subject remaining fully protected on rechallenge
      at 5 months.

PMID- 16434128
TI  - Enhancement of functional antibody responses to AMA1-C1/Alhydrogel, a Plasmodium
      falciparum malaria vaccine, with CpG oligodeoxynucleotide.
AB  - Apical membrane antigen 1 (AMA1) has been shown to be a promising malaria vaccine
      candidate. The multiallelic AMA1-C1 vaccine currently in Phase 1 trials in the US
      and Mali contains an equal mixture of the ectodomain portion of recombinant AMA1
      from the FVO and 3D7 clones of Plasmodium falciparum, formulated on Alhydrogel.
      It is hoped that inclusion of a human-optimized CpG oligodeoxynucleotide (ODN)
      (CPG 7909) with our existing AMA1-C1/Alhydrogel vaccine will lead to a higher
      concentration of functional AMA1-C1 antibodies. Preclinical studies were
      performed in mice, rats and guinea pigs to assess the safety, immunogenicity and
      functionality of the immune response to AMA1-C1 with Alhydrogel + CPG 7909
      compared to antigen with Alhydrogel alone. Day 42 mean anti-AMA1 ELISA titer
      values derived from individual animals were compared between Alhydrogel and
      Alhydrogel + CPG 7909 groups at each antigen dose for each species. Sera from
      Alhydrogel + CPG 7909 groups displayed significantly higher antibody titers (P <
      0.025) than their comparable Alhydrogel alone group. Mouse IgG isotype analysis
      showed that AMA1-C1/Alhydrogel induced a predominately Th2 type response while
      AMA1-C1/Alhydrogel + CPG 7909 gave a mixed Th1/Th2 type response. When tested for
      functional activity by in vitro inhibition of parasite invasion, IgG isolated
      from serum pools of AMA1-C1/Alhydrogel + CPG 7909 animals was more effective
      against both FVO and 3D7 parasites than an equal concentration of IgG from
      animals receiving vaccines adjuvanted with Alhydrogel alone. These promising
      preclinical results have recently led to the start of a Phase 1 trial in the US.

PMID- 16434129
TI  - Mouse model of respiratory Chlamydia pneumoniae infection for a genomic screen of
      subunit vaccine candidates.
AB  - An inbred A/J mouse respiratory challenge model was validated for vaccine testing
      against Chlamydia (C.) pneumoniae and used to screen the C. pneumoniae genome for
      vaccine candidates by expression library immunization (ELI). Biolistic delivery
      of genetic vaccine constructs elicited Th2-like immunity that was associated with
      inefficient elimination of C. pneumoniae. Delivery by injection elicited
      protective Th1-like responses. Since biolistic delivery of pools of ORFs was used
      in first round screening, the screen presumably selected against potent
      immunogens. Nevertheless, it was sufficiently accurate to identify three weakly
      protective antigens among all putative C. pneumoniae ORFs. The results suggest
      ELI discovery of highly protective C. pneumoniae vaccine candidates requires
      tight control of the Th1 immunity elicited by the genetically delivered library
      of test antigens.

PMID- 16434130
TI  - Protective effect of Bacillus Calmette-Guerin (BCG) vaccination in children with
      extra-pulmonary tuberculosis, but not the pulmonary disease. A case-control study
      in Rosario, Argentina.
AB  - A hospital-based case-control study was carried out at the Vilela Children's
      Hospital in Rosario, Argentina, to measure the protection conferred by BCG
      vaccination against tuberculosis (TB). The study included 148 newly diagnosed
      cases of TB (75 males and 73 females, mean age 3.34+/-2.97 years, S.D.), 134 of
      them with pulmonary TB and 14 cases with extra-pulmonary disease. Controls (425
      males and 357 females, 3.39+/-2.98 years) were selected randomly among children
      who attended to the Hospital showing, neither respiratory diseases nor any other
      infectious illnesses. Information on BCG vaccination history was assessed from
      scars or immunisation records. All participants were negative to human
      immunodeficiency virus and belonged to the lower and upper-lower socioeconomic
      status, being similar in place of residence and ethnic characteristics. Rate of
      vaccinated children was 92.6% of cases and 94.5% of controls (3.4 and 3.9% of
      them without scars, respectively). Regarding the total cases, the protective
      association between BCG and TB was statistically insignificant, as was for the
      pulmonary form. Among cases with extra-pulmonary disease, vaccine effectiveness
      attained significance [79% (95% CI=26-94)], no matter their age, sex or
      nutritional status. BCG vaccination exerted a beneficial role in extra-pulmonary
      TB, even in children not seriously undernourished.

PMID- 16434131
TI  - Recombinant Salmonella vaccines for biodefence.
AB  - There is a requirement for vaccines to protect against pathogens that may be
      misused for bioterrorism or biowarfare purposes. In particular, biodefence
      vaccines are required that may be used for safe and easy immunisation of
      populations and that can rapidly induce mucosal immunity to provide protection at
      the lung surface against a range of airborne agents. To address this need,
      recombinant Salmonella vaccines are being developed. In this review, the
      technologies used, considerations needed, progress made, and future prospects for
      developing multivalent Salmonella-based vaccines for biodefence are discussed.

PMID- 16434132
TI  - Pederson scale fails to predict how difficult it will be to extract lower third
      molars.
AB  - We report a consecutive series of 105 extractions of impacted lower third molars,
      in each of which operative difficulty was predicted preoperatively using the
      Pederson scale (radiographic appearance of the anatomical position of the lower
      third molar), and postoperative difficulty was scored with a modified version of
      the Parant scale (operative manoeuvres that were needed for extraction of the
      third molar). Preoperative classification as "difficult" on the Pederson scale
      was not an accurate predictor of true difficulty (postoperative classification as
      "difficult" on the modified Parant scale). There was no significant association
      between the Pederson score and duration of operation, but high Parant scores were
      significantly associated with longer operations. We suggest that scales for the
      prediction of operative difficulty in the extraction of impacted lower third
      molars should take into account factors other than the anatomical position of the
      tooth.

PMID- 16434133
TI  - Biomechanical evaluation of a dynamic pedicle screw fixation device.
AB  - BACKGROUND: Recent innovations in dynamic devices have promised a reduction in
      stress shielding, protection of adjacent segment degeneration, and decreased
      implant failure. However, there have been few studies comparing the biomechanical
      properties of a rigid device in comparison to a dynamic posterior fixation
      device. The purpose of this study was to compare the immediate stability of a new
      dynamic pedicle screw fixation device with an equivalent rigid device. METHODS:
      Six thoracolumbar cadaver spines (T10-L4) were fixed in a biomechanical testing
      frame. Pure moments of 10Nm were loaded in six directions: flexion, extension,
      right and left lateral bending, and right and left axial rotation. For each
      spine, four different stages were tested: intact, destabilization of the middle
      segment, fixation with the dynamic device, and fixation with the rigid device.
      Ranges of motion were measured using stereophotogrammetry. The specimens with
      each device were then subjected to flexion-compression loading for five cycles on
      a MTS 858 Universal Testing Machine. The average stiffness of the last three
      cycles was recorded. FINDINGS: Both dynamic and rigid devices were found to
      provide stability for the injured segment in flexion-extension and lateral
      bending. In axial rotation, the devices could restore the stability to levels
      similar to those in an intact spine. Results also indicated a slight increase in
      range of motion in flexion-extension and significant reduction in stiffness of
      flexion-compression with the dynamic device (P < 0.01), in comparison to the
      rigid device. INTERPRETATION: The dynamic device offers a system that may alter
      favorably the movement and load transmission of a spinal motion segment without
      sacrificing construct stability.

PMID- 16434134
TI  - A predictive model for copper partitioning to suspended particulate matter in
      river waters.
AB  - A chemical equilibrium-based predictive model expressing Cu partitioning as a
      function of aqueous and solid phase characteristics was developed. The model
      takes into account only the most important factors that govern Cu partitioning,
      and therefore results in a relatively simple formulation. It assumes particulate
      organic carbon (POC) and dissolved organic carbon (DOC) binding sites play the
      most important role in solid and aqueous phases. The model formulation assumed
      one-surface site and two dissolved organic matter (DOM) sites, and included the
      "solids effect". Proton effects were considered for both the particle surface
      sites and the DOM. The model was calibrated with data for samples collected from
      the Susquehanna River, and validated with White Clay Creek and Delaware River
      samples. Copper partitioning in natural water systems with different pH, and
      concentrations of alkalinity, DOC, POC, total suspended solids (TSS), and total
      copper was predicted reasonably well.

PMID- 16434136
TI  - Tumour features in the control and screening arm of a randomized trial of
      prostate cancer.
AB  - OBJECTIVE: To compare tumour characteristics at the time of diagnosis of cancers
      detected in the screening and control arm at the Rotterdam section of the
      European Randomized study of Screening for Prostate Cancer. METHODS: Data were
      retrieved from the Rotterdam section of the ERSPC. Men were randomized to the
      screening arm (n=21,210) or the control arm (n=21,166). Men randomized to
      screening were offered PSA testing every 4 years. Through linkage with the cancer
      registry, men randomized to the control arm were detected. The biopsy Gleason
      score was determined in 1,591 and 373 patients in the screening and control arm,
      respectively. TURP, radical prostatectomy (RP) and cystoprostatectomy were
      evaluated for Gleason score, pathological (p)T stage and tumour volume. RESULTS:
      More prostate cancers were detected in the screening arm (15.9 vs. 4.2 per 1000
      man years, p<0.0001). Clinical stage distribution as well as biopsy and RP
      Gleason score distribution were significantly less favourable in the control arm.
      The incidence in man years of advanced disease (i.e. T4/N1/M1) was higher in the
      screening arm (6.0 per 100,000) as compared to the control arm (4.6 per 100,000).
      The 5-year PSA progression free survival after RP was 68% in the control arm and
      89% in the screening arm (p<0.0001). The proportion of Incidental prostate
      cancers was 9.3% of all cancers detected in the control arm. CONCLUSIONS:
      Although the number of men with advanced prostate cancer is slightly higher in
      the screening arm, the proportion of prostate cancers with favourable features is
      increased in the screening arm as compared to that in the control arm.

PMID- 16434137
TI  - GINsim: a software suite for the qualitative modelling, simulation and analysis
      of regulatory networks.
AB  - This paper presents GINsim, a Java software suite devoted to the qualitative
      modelling, analysis and simulation of genetic regulatory networks. Formally, our
      approach leans on discrete mathematical and graph-theoretical concepts. GINsim
      encompasses an intuitive graph editor, enabling the definition and the
      parameterisation of a regulatory graph, as well as a simulation engine to compute
      the corresponding qualitative dynamical behaviour. Our computational approach is
      illustrated by a preliminary model analysis of the inter-cellular regulatory
      network activating Notch at the dorsal-ventral boundary in the wing imaginal disc
      of Drosophila. We focus on the cross-regulations between five genes (within and
      between two cells), which implements the dorsal-ventral border in the developing
      imaginal disc. Our simulations qualitatively reproduce the wild-type
      developmental pathway, as well as the outcome of various types of experimental
      perturbations, such as loss-of-function mutations or ectopically induced gene
      expression.

PMID- 16434138
TI  - Role of Brassica juncea (L.) Czern. (var. Vaibhav) in the phytoextraction of Ni
      from soil amended with fly ash: selection of extractant for metal
      bioavailability.
AB  - A pot experiment was carried out to study the potential of the plant of Brassica
      juncea for the phytoextraction of metal from fly ash amended soil and to study
      correlation between different pool of metals (total, DTPA, CaCl(2) and
      NH(4)NO(3)) and metal accumulated in the plant in order to assess better
      extractant for plant available metals. The results of total metal analysis in the
      soil revealed the presence of Cr, which was found below detection limit (BDL) in
      the plants. The fly ash (FA) amendments and soil samples were extracted with
      different extractants and the level of metal vary from one extractant to another.
      The regression analysis between total and extractable metals showed better
      regression for all the tested metals except Mn (R(2)=0.001) in DTPA extraction.
      Correlation coefficient between metal accumulation by the plant tissues and
      different pool of metals showed better correlation with DTPA in case of Fe, Zn
      and Ni, whereas, Cu was significantly correlated with NH(4)NO(3) and other metals
      (Pb, Mn) with CaCl(2). The soil analysis results revealed that the mobility and
      plant availability of metals (Fe, Mn, Zn, Ni) within the profiles of amended
      soils was influenced by the change in pH, however, Pb and Cu was not affected.
      The metal accumulation in total plant tissues was found in the order of
      Fe>Ni>Zn>Mn>Cu>Pb and its translocation was found more in upper part. The plants
      grown on soil amended with 25%FA have shown significant increase in plant
      biomass, shoot and plant height, whereas, no significant effect was observed in
      root length. The cluster analysis showed 10%FA behave differently on the basis of
      physico-chemical properties and metal behavior. Thus, it may be concluded that B.
      juncea can be used for phytoextraction of metals, especially Ni in fly ash
      amendment soil.

PMID- 16434139
TI  - Biosorption of Acid Blue 290 (AB 290) and Acid Blue 324 (AB 324) dyes on
      Spirogyra rhizopus.
AB  - In this study, the biosorption of Acid Blue 290 and Acid Blue 324 on Spirogyra
      rhizopus, a green algae growing on fresh water, was studied with respect to
      initial pH, temperature, initial dye concentration and biosorbent concentration.
      The optimum initial pH and temperature values for AB 290 and AB 324 biosorption
      were found to be 2.0, 30 degrees C and 3.0, 25 degrees C, respectively. It was
      observed that the adsorbed AB 290 and AB 324 amounts increased with increasing
      the initial dye concentration up to 1500 and 750 mg/L, respectively. The
      Langmuir, Freundlich, Redlich-Peterson and Koble-Corrigan isotherm models were
      applied to the experimental equilibrium data and the isotherm constants were
      determined by using Polymath 4.1 software. The monolayer coverage capacities of
      S. rhizopus for AB 290 and AB 324 dyes were found as 1356.6 mg/g and 367.0 mg/g,
      respectively. The intraparticle diffusion model and the pseudo-second order
      kinetic model were applied to the experimental data in order to describe the
      removal mechanism of these acidic dyes by S. rhizopus. The pseudo-second order
      kinetic model described very well the biosorption kinetics of AB 290 and AB 324
      dyes. Thermodynamic studies showed that the biosorption of AB 290 and AB 324 on
      S. rhizopus was exothermic in nature.

PMID- 16434140
TI  - Solubilization and immunopurification of rat brain synaptic vesicle protein 2A
      with maintained binding properties.
AB  - This study reports the solubilization of the rat synaptic vesicle protein SV2A,
      the brain binding site for the antiepileptic drug levetiracetam (LEV), and its
      characterization. N-dodecyl-beta-D-maltoside (DDM) was the best detergent at
      achieving a high percentage of SV2A solubilization and at maintaining the binding
      characteristics of a tritiated form of a more potent analogue of LEV, [3H]ucb
      30889 ((2S)-2-[4-(3-azidophenyl)-2-oxopyrrolidin-1-yl]butanamide). Scatchard
      analysis revealed that approximately 25% of SV2A proteins from brain membranes
      are solubilized by DDM under optimal conditions. Competition binding experiments
      with a variety of LEV analogues indicated that [3H]ucb 30889 labels the same
      binding site in both crude homogenates and soluble extracts, with still high
      stereoselectivity. After immunoprecipitation of SV2A from solubilized rat brain
      membranes, binding properties of [3H]ucb 30889 to SV2A and association with
      synaptotagmin I were maintained. The two other isoforms SV2B and SV2C were found
      to be co-immunoprecipitated with SV2A. The solubilization and immunopurification
      of SV2A with unmodified ligand affinities and synaptotagmin I interaction
      provides the starting point for future protein-protein interactions and
      structural studies.

PMID- 16434141
TI  - Voltage-dependent potassium channels are involved in glutamate-induced apoptosis
      of rat hippocampal neurons.
AB  - The role of voltage-dependent potassium channel currents in glutamate-treated rat
      hippocampal neurons was investigated. Cell viability was evaluated by MTT
      reduction assay and morphological changes. Apoptosis was detected by Hoechst33342
      staining with fluorescent microscopy and propidium iodide staining with flow
      cytometry. Membrane potassium channel currents were recorded with whole-cell
      patch clamp recordings. Results showed that after shortly exposed to glutamate,
      about 25 and 50% cells died in 3 h and 24 h, respectively. Meanwhile, the
      enhancement of IK was observed within 6 h after the glutamate insult. TEA
      selectively blocked IK and significantly reduced cell apoptosis. IA did not
      change in the insult though 4-AP, the blocker of this current, showed a
      protective effect against the injury. These data were in consistent with the
      hypothesis that K+ efflux contributed to glutamate-triggered apoptosis and IK
      channels might have a therapeutic effect on the treatment of cerebral ischemia.

PMID- 16434142
TI  - Clinical field efficacy and safety of pyrantel pamoate paste (19.13% w/w pyrantel
      base) against Anoplocephala spp. in naturally infected horses.
AB  - Clinical field trials were conducted at five geographical locations in the USA
      (Oklahoma, Wisconsin, Tennessee, Virginia and Idaho) to evaluate the efficacy and
      safety of pyrantel pamoate paste (19.13%, w/w, pyrantel base) administered at the
      recommended dosage of 13.2 mg pyrantel base/kg (6.0 mg pyrantel base/lb) body
      weight (b.w.) against tapeworm infections of Anoplocephala spp. in naturally
      infected horses. Horses at each study site were allocated by restricted
      randomization based on the cestode status (positive or negative) of pre-treatment
      fecal egg counts to complete sets of four animals each or incomplete sets of
      fewer than four animals. Within sets comprising of two to four horses, one animal
      was randomly allocated to receive placebo vehicle paste and the remaining
      horse(s) received pyrantel pamoate paste administered orally at a minimum dosage
      of 13.2 mg pyrantel base/kg b.w. on Test Day (TD) 0. Single animal sets received
      pyrantel pamoate paste. Fecal samples of horses were collected and examined for
      equine tapeworm (Anoplocephala spp.) eggs a minimum of four times (once or thrice
      between TD -28 and -14, twice between TD -14 and -7, and once on TD 0) prior to
      treatment on TD 0. Fecal samples of horses that were positive for cestode
      infection pre-treatment were examined for cestode eggs on TD 7, 8, 9, 14, 15 and
      16. Cestode-negative pre-treatment horses were not sampled again after treatment.
      A total of 241 horses (141 mares, 16 stallions and 84 geldings; 6 months-30 yrs
      of age; 173-646 kg; 13 recognized breeds and various crossbreds) were evaluated.
      The prevalence of Anoplocephala spp. determined by pre-treatment fecal
      examination ranged from 38.3% in Idaho to 68.1% in Tennessee with an overall
      prevalence of 52.3%. Ninety cestode-positive and 88 cestode-negative horses were
      treated with pyrantel pamoate paste, 36 cestode-positive and 27 cestode-negative
      horses were treated with placebo vehicle paste. Overall, 178 horses were treated
      with pyrantel pamoate paste, and 63 horses were treated with placebo paste. Of
      the 178 horses treated with pyrantel pamoate paste, no drug related, adverse
      clinical or neurological health events were observed. No doses of pyrantel
      pamoate paste were refused or lost during dosing. At each post-treatment time
      sampling interval, significantly fewer cestode eggs (P < 0.0115) were passed by
      cestode-positive horses treated with pyrantel pamoate paste compared to cestode
      positive horses that received placebo paste. Efficacy of the pyrantel pamoate
      paste treatment ranged from 92 to 96% from TD 7 to TD 16 with an overall efficacy
      of 95%. The results of these trials demonstrated that pyrantel pamoate paste
      (19.13%, w/w, pyrantel base) administered orally at a dosage of 13.2 mg pyrantel
      base/kg b.w. is highly efficacious (95%) against Anoplocephala spp. and safe for
      use in horses with no adverse clinical or neurological health events observed
      under field use conditions.

PMID- 16434143
TI  - High-quality evidence in oncology from 16 June to 18 August 2005: a summary.

PMID- 16434145
TI  - It does the job: Young adults discuss their malt liquor consumption.
AB  - Young adult men and women (N=53) who regularly consume malt liquor (i.e., 40
      oz/week) participated in 10 semi-structured focus groups. Group transcripts were
      analyzed using a multilevel process that focused on recurring themes across
      multiple groups. Commonly identified themes encompassed positive and negative
      qualities of malt liquor as well as contexts in which malt liquor was consumed.
      Some of the themes were corroborated by quantitative data on drinking behavior
      and other variables. The focus groups were designed to explore the unique
      characteristics of malt liquor (low price, high alcohol content, large volume
      packaging) that enhance consumption patterns and increase risk for excessive
      alcohol use. The combination of qualitative and quantitative data provides a
      unique and useful perspective for identifying issues for future research on malt
      liquor consumption.

PMID- 16434144
TI  - Combined pre- and postnatal environmental enrichment programs the HPA axis
      differentially in male and female rats.
AB  - Experimental environmental enrichment (EE) is usually applied in adulthood or
      immediately after weaning, with robust effects on physiology and behaviour. To
      investigate the effects of EE earlier in life, female rats were maintained under
      moderate enrichment during pregnancy and, together with their pups, during
      lactation until weaning. A separate group of dams housed under standard
      conditions during pregnancy and lactation served as controls. Dams housed under
      EE exhibited fewer nursing episodes and were off the nest more often, but the
      frequency of pup licking was not affected on postnatal days 3-5. EE effects on
      hypothalamus-pituitary-adrenal (HPA) axis responses to an acute stressor were
      determined in adult male and female offspring with and without previous exposure
      to the chronic stressor of constant light. In female offspring, chronic stress
      significantly increased basal corticosterone (CORT) levels, but not if rats had
      been exposed to early EE. Furthermore, while control females exposed to chronic
      stress showed a greatly reduced adrenocorticotropin (ACTH) response to an acute
      stressor, EE females did not display this desensitization. There was no
      significant effect of EE on basal ACTH and CORT levels in adult male offspring,
      nor did it alter their response to acute stress. Maternal licking frequency was
      moderately but significantly correlated with net corticosterone increases in
      response to acute stress, the direction of the correlation crucially depending on
      the offspring's sex and stress conditions. This study shows that EE during
      pregnancy and lactation has long-lasting effects on reactivity to acute and
      chronic stress in offspring and that these effects are dependent on the
      offspring's sex but not greatly on early postpartum maternal behaviour.

PMID- 16434146
TI  - Essential hypertension seems to result from melatonin-induced epigenetic
      modifications in area postrema.
AB  - Essential hypertension is a complex multifactorial disorder with epigenetic and
      environmental factors contributing to its prevalence. Epigenetic system is a
      genetic regulatory mechanism that allows humans to maintain extraordinarily
      stable patterns of gene expression over many generations. Sympathetic nervous
      system plays a major role in the maintenance of hypertension and the rostral
      ventrolateral medulla is the main source of this sympathetic activation. A
      possible mechanism to explain the sympathetic hyperactivity in the rostral
      ventrolateral medulla is an action of the area postrema. Area postrema seems to
      be the region where a shift of the set-point to a higher operating pressure
      occurs resulting in hypertension. But, how can a shift occur in the area
      postrema. We propose that melatonin-induced epigenetic modifications in the
      neurons of area postrema plays a role in this shift. Area postrema is reported to
      contain high levels of melatonin receptors that play a role in the epigenetic
      modifications in certain cells. Environmental stressors cause epigenetic
      modifications in the neurons of area postrema via the pineal hormone melatonin
      and these changes lead to a shift in the set-point to a higher operating
      pressure. This signal is then sent via efferent projections to key medullary
      sympathetic nuclei in rostral ventrolateral medulla resulting in increases in
      sympathetic nerve activity. This model may explain the long-term alterations in
      sympathetic activity in essential hypertension.

PMID- 16434148
TI  - Zinc-levamisole combination: Powerful synergistic immunopotentiation?

PMID- 16434147
TI  - Activated protein C and the ovarian hyperstimulation syndrome: possible
      therapeutic implications.
AB  - Given the efficacy and safety of recombinant human activated protein C (rhAPC) in
      the systemic inflammatory response syndrome (SIRS), this study was designed to
      review the evidence for rhAPC as a possible therapeutic option in the treatment
      of severe ovarian hyperstimulation syndrome (OHSS). SIRS, like OHSS, is a
      proinflammatory and prothrombotic disorder whose cornerstone is endothelial
      dysfunction in which protein C deficiency is a frequent occurrence. Recently, the
      use of rhAPC has been shown to be of benefit with a reduction in mortality and an
      improvement in indicators of inflammation and coagulation. OHSS is typically an
      iatrogenic disorder resulting from ovarian stimulation as a component of
      infertility treatment. The pathogenesis of OHSS, like sepsis, is related to
      endothelial dysfunction and inflammation and can result in significant morbidity
      including end organ hypoperfusion, disseminated intravascular coagulation (DIC),
      thrombosis, and occasionally, death. We have performed a review of the literature
      to identify similarities between these disease processes to develop a theoretical
      basis for the use of rhAPC in patients with moderate to severe OHSS. Use of rhAPC
      in this group may attenuate the disease process and reduce the potential
      morbidity associated with this iatrogenic disorder.

PMID- 16434149
TI  - Meditation potentially capable of increasing susceptibility to epilepsy - a
      follow-up hypothesis.
AB  - In an earlier article entitled "Meditation may predispose to epilepsy: an insight
      into the alteration in brain environment induced by meditation" published in
      Medical Hypotheses 2005:64(3):464-7, the author has hypothesized that meditation
      exerts predisposing influence on epileptogenesis. The hypothesis is based on
      certain EEG changes and electrographic features (namely hypersynchrony and
      coherence of EEG activity) and increase in chemical transmitters (namely
      glutamate and serotonin) in the brain during the course and attainment of
      meditation. This paper aims to further strengthen the hypothesized predisposing
      influence of meditation on epilepsy by providing stronger evidences and with more
      elaboration. Studies on meditators have reported various adverse outcomes and one
      such study has indeed revealed significantly higher incidence of complex partial
      epileptic-like signs and experiences in a large number (n = 221) of meditators
      compared to non-meditators (controls n = 860), the researcher claiming "cognitive
      kindling" by meditation to be the underlying basis. These studies thus do
      highlight and underscore the strong influence of meditation in increasing
      susceptibility to epilepsy.

PMID- 16434150
TI  - Counting in a time discrimination task in children and adults.
AB  - The present study investigated in 5- and 8-year-olds, as well as in adults, the
      effect of verbal counting on temporal discrimination behavior in a generalization
      task with two duration ranges in order to test the scalar timing property. The
      results showed that counting improved temporal sensitivity in all age groups,
      although sensitivity to time remained lower in the younger children. Furthermore,
      in the 5-year-olds, the temporal generalization behavior conformed well to the
      scalar property of variance both in the counting and the non-counting condition.
      However, this conformity to the scalar timing property disappeared when counting
      was used in the 8-year-olds and the adults. The development of the ability to
      count time at a constant rhythm is discussed as the major reason for this
      departure of temporal behavior from the scalar property of variance when counting
      is employed.

PMID- 16434151
TI  - A right hemispheric prefrontal system for cognitive time measurement.
AB  - Despite a growing body of neuroimaging data, little consensus has been reached
      regarding the neural correlates of temporal processing in humans. This paper
      presents a reanalysis of two previously published neuroimaging experiments, which
      used two different cognitive timing tasks and examined both sub- and supra-second
      intervals. By processing these data in an identical manner, this reanalysis
      allows valid comparison and contrasting across studies. Conjunction of these
      studies using inclusive masking reveals shared activity in right hemispheric
      dorsolateral and ventrolateral prefrontal cortex and anterior insula, supporting
      a general-purpose system for cognitive time measurement in the right hemispheric
      prefrontal cortex. Consideration of the patterns of activity in each dataset with
      respect to the others, and taking task characteristics into account, provides
      insight into the possible role of dorsolateral prefrontal cortex in working
      memory and of posterior parietal cortex and anterior cingulate in attentional
      processing during cognitive time measurement tasks.

PMID- 16434152
TI  - Directed evolution of extradiol dioxygenase by a novel in vivo DNA shuffling.
AB  - RecA-dependent homologous recombination in Escherichia coli is a very effective
      way to construct chimeras between two homologous genes. The disadvantage of in
      vivo method is a small library size of chimeric genes in comparison with in vitro
      DNA shuffling. In order to overcome the disadvantage, we have developed novel in
      vivo DNA shuffling methods with successive homologous recombinations. Linearized
      DNA molecules with two homologous genes were made with ligation rather than the
      conventional restriction enzyme cleavage between two genes. The three-way
      ligation of a vector and two homologous bphC genes encoding 2,3-dihydroxybiphenyl
      1,2-dioxygenases or the two-way ligation of the donor bphC gene and an acceptor
      plasmid carrying the homologous bphC gene generated a variety of linearized DNA
      molecules. The homologous recombination between the genes on the linearized DNA
      molecules created the large chimeric bphC gene libraries in a recBC sbcA E. coli
      strain. After three rounds of recombinations, chimeric bphC genes with four-part
      gene fragments by triple-crossover were easily obtained. By employing a 96-well
      microtiter plate high-throughput screening, thermally stable chimeric 2,3
      dihydroxybiphenyl 1,2-dioxygenases were selected from chimeric bphC gene
      libraries. This opens up a new way for directed evolution of proteins in vivo.

PMID- 16434153
TI  - Evolutionary origins of the endocannabinoid system.
AB  - Endocannabinoid system evolution was estimated by searching for functional
      orthologs in the genomes of twelve phylogenetically diverse organisms: Homo
      sapiens, Mus musculus, Takifugu rubripes, Ciona intestinalis, Caenorhabditis
      elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Arabidopsis thaliana,
      Plasmodium falciparum, Tetrahymena thermophila, Archaeoglobus fulgidus, and
      Mycobacterium tuberculosis. Sequences similar to human endocannabinoid exon
      sequences were derived from filtered BLAST searches, and subjected to
      phylogenetic testing with ClustalX and tree building programs. Monophyletic
      clades that agreed with broader phylogenetic evidence (i.e., gene trees
      displaying topographical congruence with species trees) were considered
      orthologs. The capacity of orthologs to function as endocannabinoid proteins was
      predicted with pattern profilers (Pfam, Prosite, TMHMM, and pSORT), and by
      examining queried sequences for amino acid motifs known to serve critical roles
      in endocannabinoid protein function (obtained from a database of site-directed
      mutagenesis studies). This novel transfer of functional information onto gene
      trees enabled us to better predict the functional origins of the endocannabinoid
      system. Within this limited number of twelve organisms, the endocannabinoid genes
      exhibited heterogeneous evolutionary trajectories, with functional orthologs
      limited to mammals (TRPV1 and GPR55), or vertebrates (CB2 and DAGLbeta), or
      chordates (MAGL and COX2), or animals (DAGLalpha and CB1-like receptors), or
      opisthokonta (animals and fungi, NAPE-PLD), or eukaryotes (FAAH). Our methods
      identified fewer orthologs than did automated annotation systems, such as
      HomoloGene. Phylogenetic profiles, nonorthologous gene displacement, functional
      convergence, and coevolution are discussed.

PMID- 16434154
TI  - Cloning and characterization of the astaxanthin biosynthesis gene cluster from
      the marine bacterium Paracoccus haeundaensis.
AB  - Carotenoids are important natural pigments produced by many microorganisms and
      plants. In a previous study, we isolated and characterized a marine bacterium,
      Paracoccus haeundaensis, which produces carotenoids, mainly astaxanthin. In the
      present study, a carotenoid biosynthesis gene cluster involved in the production
      of astaxanthin was isolated and characterized from this marine bacterium. The
      cluster contained six carotenogenic genes, five of which, with the same
      orientation, were designated crtW, crtZ, crtY, crtI, and crtB, and one of which,
      with the opposite orientation, was designated crtE. The crtW, crtZ, crtY, crtI,
      crtB, and crtE genes contained 726, 486, 1158, 1503, 912, and 879 base pairs,
      respectively, and encoded polypeptides of 242, 162, 386, 501, 304, and 293 amino
      acid residues, respectively. The stop codon of each crt gene, except crtE,
      overlapped the start codon of the following crt gene. Comparisons of the
      structures and nucleotide sequences of the crt genes showed that the signature
      domains of the carotenoid biosynthesis genes are highly conserved. The molecular
      phylogenetic tree analysis showed the evolutionary relationships among the
      carotenoid biosynthesis genes of various organisms. An expression vector (pCR-XR
      TOPO-Crt-full vector) containing the astaxanthin biosynthesis genes was
      constructed and transformed into Escherichia coli BL21(DE3) Codon Plus cells. The
      E. coli transformants produced 400 microg astaxanthin per gram of dry cell
      weight.

PMID- 16434155
TI  - Evaluation of human serum albumin as a substitute of foetal bovine serum for cell
      culture.
AB  - Cell microencapsulation requires clinically approved materials for their use in
      pharmaceutical and/or biomedical applications. The overwhelming majority of the
      literature has used the classical alginate-poly-l-lysine-alginate (APA) capsules
      for cell immobilization. Although alginate is granted with the medical approval,
      some of the remaining components such as foetal bovine serum (FBS), an essential
      ingredient of cell culture media, are not in accordance with the guidelines
      affirmed by the American Society for Testing and Materials (ASTM) and Food and
      Drug Administration (FDA). In this paper, human serum albumin (HSA), a medically
      approved substance, was evaluated as a potential substitute of FBS. The effect of
      different percentages of FBS and HSA was studied on the proliferation rate,
      viability and protein production of two different cell lines (C2C12 and baby
      hamster kidney (BHK) cells), maintained in culture and immobilized in APA
      microcapsules. Results show that substitution of FBS by HSA reduced the
      functionality of both non-encapsulated and encapsulated BHK cells. However,
      immobilized C2C12 cells presented the highest level of viability and a reduction
      in protein production of 25% when 1% HSA was used. It can be concluded that HSA
      might be a possible substitute of FBS in order to maintain or transport
      encapsulated C2C12 cells for short periods of time before implantation.

PMID- 16434156
TI  - Modulated release of bioactive protein from multilayered blended PLGA coatings.
AB  - The objective of this study was to develop a poly(D,L-lactic-co-glycolic acid)
      (PLGA)-based coating system for producing biologically-inspired delivery
      profiles. Protein-loaded microspheres were made from PLGA (50:50) terminated with
      carboxylic acid groups (PLGA-2A) blended either with more hydrophobic PLGA
      (50:50) having lauryl ester endcaps (PLGA-LE) or with the more hydrophilic
      Pluronic F-127 (PF-127). Dense coatings were formed by pressure-sintering the
      microspheres. Altering hydrophobicity changed the water concentration within
      coatings, and consequently the time to onset of polymer degradation and protein
      release was modulated. After blending up to 8% Pluronic, degradation by-products
      began accumulating immediately upon incubation in saline, whereas, degradation
      was delayed for up to 14 days with blending of up to 30% PLGA-LE. Primary protein
      release peaks from one-layer coatings could be created from 7 to 20 days using 8%
      PF-127 or 30% PLGA-LE blends, respectively. Multilayered coatings of different
      blends generated several release peaks, with their temporal occurrence remaining
      approximately the same when layers of other hydrophobicity were added above or
      below. To allow design of coatings for future use, results were used to construct
      a model based on Fourier analysis. This polymer blend system and model can be
      used to mimic temporally varying profiles of protein expression.

PMID- 16434157
TI  - Evaluation of rapidly disintegrating tablets containing glycine and
      carboxymethylcellulose.
AB  - A rapidly disintegration tablet in the oral cavity was prepared using a glycine
      as a disintegrant. Effect of disintegrant on the disintegration behavior of the
      tablet in the oral cavity was evaluated. Wetting time prepared from
      carboxymethylcellulose (NS-300) having the hardness of 4 kg was 3 s. Tablet
      containing NS-300 showed fastest disintegration compared to other formulations.
      These results suggested that NS-300 possessed excellent wetting nature and
      resulted in the rapid disintegration of tablet. Ethenzamide and ascorbic acid
      were added to the formulation, and their disintegration behavior were evaluated.
      Ethenzamide did not affect the disintegration property, however, ascorbic acid
      prolonged disintegration time. It was suggested that the tablet formulation
      containing NS-300 and glycine was highly applicable to water-insoluble drug, such
      as ethenzamide.

PMID- 16434158
TI  - Threshold minima and maxima in the behavioral audiograms of the bats Artibeus
      jamaicensis and Eptesicus fuscus are not produced by cochlear mechanics.
AB  - Behavioral audiograms of Artibeus jamaicensis and Eptesicus fuscus are
      characterized by two threshold minima separated by a threshold maximum at 40 kHz,
      for A. jamaicensis, and 45 kHz, for E. fuscus [Koay, G., Heffner, H.E., Heffner
      R.S., 1997. Audiogram of the big brown bat (Eptesicus fuscus). Hear. Res. 105,
      202-210; Heffner, R.S., Koay, G., Heffner H.E., 2003. Hearing in American leaf
      nosed bats. III: Artibeus jamaicensis. Hear. Res. 184, 113-122.]. To investigate
      whether these characteristics are due to cochlear properties, we recorded
      distortion product otoacoustic emissions (DPOAEs) and calculated DPOAE threshold
      curves. We found that in both species cochlear sensitivity, assessed by DPOAE
      recordings, does not show local threshold maxima. The DPOAE threshold curve
      calculated for A. jamaicensis reveals a broadly tuned minimum for frequencies
      between 20 and 50 kHz and the threshold curve of E. fuscus shows a broad
      sensitive area for frequencies between 15 and 60 kHz. In none of the two species
      any pronounced threshold irregularities were found. The characteristic pattern of
      a threshold maximum followed by a minimum observed in behavioral studies seems to
      be shaped by transfer characteristics of the outer ear and/or neuronal processing
      in the ascending auditory pathway rather than by cochlear mechanics.

PMID- 16434159
TI  - Assessment of chest pain in the emergency room: what is the role of multidetector
      CT?
AB  - Chest pain is one of the most frequent complaints for patients seen in the
      emergency department. The current article describes the clinical stratification
      of patients who present to the emergency department with chest pain and discusses
      imaging options and analysis for these patients. It reviews conventional imaging
      approaches to assessing chest pain including chest radiography and stress
      testing. The main discussion focuses on the potential utility use of cross
      sectional imaging, particularly multidetector CT, in the evaluation of chest pain
      in the emergency department.

PMID- 16434160
TI  - Evidence for lower variability of coronary artery calcium mineral mass
      measurements by multi-detector computed tomography in a community-based cohort-
      consequences for progression studies.
AB  - PURPOSE: To compare the measurement variability for coronary artery calcium (CAC)
      measurements using mineral mass compared with a modified Agatston score (AS) or
      volume score (VS) with multi-detector CT (MDCT) scanning, and to estimate the
      potential impact of these methods on the design of CAC progression studies.
      MATERIALS AND METHODS: We studied 162 consecutive subjects (83 women, 79 men,
      mean age 51 +/- 11 years) from a general Caucasian community-based cohort
      (Framingham Heart Study) with duplicate runs of prospective
      electrocardiographically-triggered MDCT scanning. Each scan was independently
      evaluated for the presence of CAC by four experienced observers who determined a
      "modified" AS, VS and mineral mass. RESULTS: Of the 162 subjects, CAC was
      detected in both scans in 69 (42%) and no CAC was detected in either scan in 72
      (45%). Calcium scores were low in the 21/162 subjects (12%) for whom CAC was
      present in one but not the other scan (modified AS < 20 in 20/21 subjects, mean
      AS 4.6 +/- 1.9). For all three quantification algorithms, the inter- and
      intraobserver correlation were excellent (r > 0.96). However, the mean interscan
      variability was significantly different between mineral mass, modified AS, and VS
      (coefficient of variation 26 +/- 19%, 41 +/- 28% and 34 +/- 25%, respectively; p
      < 0.04), with significantly smaller mean differences in pair-wise comparisons for
      mineral mass compared with modified AS (p < 0.002) or with VS (p < 0.03). The
      amount of CAC but not heart rate was an independent predictor of interscan
      variability (r = -0.638, -0.614 and -0.577 for AS, VS, and mineral mass,
      respectively; all p < 0.0001). The decreased interscan variability of mineral
      mass would allow a sample size reduction of 5.5% compared with modified AS for
      observational studies of CAC progression and for randomized clinical trials.
      CONCLUSION: There is significantly reduced interscan variability of CAC
      measurements with mineral mass compared with the modified AS or VS. However, the
      measurement variability of all quantification methods is predicted by the amount
      of CAC and is inversely correlated to the extent of partial volume artifacts.
      Moreover, the improvement of measurement reproducibility leads to a modest
      reduction in sample size for observational epidemiological studies or randomized
      clinical trials to assess the progression of CAC.

PMID- 16434161
TI  - Mapping epicardial fat with multi-detector computed tomography to facilitate
      percutaneous transepicardial arrhythmia ablation.
AB  - A sizable portion of ventricular tachycardia circuits are epicardial, especially
      in patients with non-ischemic cardiomyopathy, e.g. Chagas disease. Thus there is
      a growing interest among the electrophysiologists in transepicardial mapping and
      myocardial ablation for treatment of arrhythmias. However, increased epicardial
      fat can be a significant hindrance in procedural success as it can mimic infarct
      during mapping and can also decrease the effectiveness of ablation. Quantitative
      knowledge of epicardial fat pre-procedure can potentially significantly
      facilitate the conduct and outcomes of these procedures. In this study we
      assessed the epicardial fat distribution and thickness in vivo in 59 patients who
      underwent multi-detector computed tomography (MDCT) for coronary artery
      assessment using a 16-slice scanner. Multiplanar reconstructions were obtained in
      the ventricular short axis at the basal, mid ventricular, and near the apex
      level, and in a four-chamber view. In the short axis slices, we measured
      epicardial fat diameter in nine segments, and in the four-chamber view, it was
      measured in five segments. In grooved segments the maximum fat thickness was
      recorded, while in non-grooved segments thickness at three equally spaced points
      were averaged. The results were as follows starting clockwise: superior inter
      ventricular (IV) groove (all measurements are in mm, in basal, mid ventricular,
      and apical levels, respectively) (11.2, 8.6, 7.3), left ventricular (LV) superior
      lateral wall (1.0, 1.5, 1.7), LV inferior lateral wall (1.3, 2.2, 3.5), inferior
      IV groove (9.2, 6.5, 6.1), right ventricular (RV) diaphragmatic wall (1.4, 0.2,
      1.0), acute margin (9.2, 7.3, 7.8), RV anterior free wall inferior (6.8, 4.0,
      4.7), RV anterior free wall superior (6.5, 3.2, 3.1), RV superior wall (5.6, 2.7,
      4.0), We measured the following four-chamber segments: LV apex (2.8 mm), left
      atrio-ventricular (AV) groove (12.7), right AV groove (14.8), RV apex (4.8), and
      anterior IV groove (7.7). The mean epicardial fat thickness for all cases was 5.3
      mm (S.D. 1.6). The mean total epicardial fat for patients over 65 was 22% greater
      than younger patients, with a 36% increase along the RV anterior free wall, 57%
      along the RV diaphragmatic wall and 38% along the LV lateral wall. Women averaged
      17% more total epicardial fat. In conclusion, this study was designed to provide
      an epicardial fat map for physicians performing percutaneous epicardial mapping
      and interventions. While the acute margin and RV anterior free wall tend to have
      high epicardial fat, and the LV lateral wall and RV diaphragmatic wall tend to
      have little to no fat, there is significant variation between patients. MDCT is a
      reliable modality for visualizing epicardial fat, and should be considered prior
      to undergoing procedures that are affected by epicardial fat content, especially
      in elderly and female populations.

PMID- 16434162
TI  - Assessment and mathematical modeling of glucose turnover and insulin sensitivity
      in lean and obese cats.
AB  - Insulin sensitivity (SI) of glucose disposal can be quantified with the
      euglycemic hyperinsulinemic clamp (EHC) with tracer glucose infusion. True steady
      state is, however, difficult to achieve, and non-steady state analysis of EHC
      data is preferred. This analysis requires information on glucose kinetics that
      can be obtained from bolus injection of cold and tracer glucose. The aim of this
      study was to assess glucose kinetics in cats. Mathematical modeling and non
      steady state analysis was applied to assess effects of obesity on glucose
      turnover, glycolysis/glycogen synthesis, SI, and inhibition of endogenous glucose
      production (EGP) in lean cats (L) and obese cats (O). D-[3-(3)H]-glucose kinetics
      and 3H-H2O production were analyzed in 4 L and 4 O with three-compartment
      modeling. Frequently sampled insulin-modified intravenous glucose tolerance tests
      (FSIGT) with minimal model analysis were performed in 5L and 3 O to assess
      glucose kinetics and SI. EHC was performed in 10 L and 10 O with primed-constant
      infusion of 3H-glucose. Data were analyzed with a modified minimal model
      segregating suppression of EGP by insulin using a non-linear mixed-effects
      population approach. FSIGT provided estimates of SI, glucose effectiveness SG,
      and distribution volume. EHC provided estimates of SI, SG, glycolysis, and
      suprabasal insulin concentration for 50% EGP inhibition. Obesity appears to
      affect glucose distribution but not utilization at basal insulin, and reduces SI
      estimated by FSIGT and EHC. Differences in SI between FSIGT and EHC depend on
      different descriptions of EGP inhibition by insulin. Finally, glucose disposal at
      basal insulin appears to occur entirely through glycolysis, whereas significant
      amounts of glucose are sequestrated from oxidation during EHC.

PMID- 16434163
TI  - Extended right-sided liver resection for colorectal liver metastases--impact of
      percutaneous portal venous embolisation.
AB  - AIM: To compare the outcome after extended right liver lobe resection (ERL) for
      patients with liver metastases from colorectal cancer with preceding portal vein
      embolisation (PVE) with a non-PVE-group. METHODS: Nineteen patients underwent ERL
      (resection of segment 4-8) for colorectal liver metastases after PVE. They were
      compared with 21 patients that underwent an ERL without embolisation. A
      comparison was made with 84 patients undergoing right lobe liver resection during
      the same time period. Survival, post-operative morbidity and mortality were
      recorded and the volume of the future remnant liver (FRL) was measured with CT.
      RESULTS: There were major complications in 1/19 patients in the PVE-group and in
      6/21 in the non-PVE-group (p=0.04). No post-operative deaths were observed in the
      PVE-group, compared to three deaths in the non-PVE-group (p=0.09). The median
      survival in the PVE-group was 32 months, which did not differ from the non-PVE
      group. In 21% of the patients that underwent PVE, progression occurred during the
      time between embolisation and surgery. There was no difference in survival for
      patients that underwent PVE followed by ERL, compared to patients that underwent
      standard right lobe liver resection. CONCLUSION: The survival of patients after
      ERL is comparable with patients that undergo standard right lobe resection and
      have less liver tumour.

PMID- 16434164
TI  - Overlapping and distinct transcriptional regulator properties of the GLI1 and
      GLI2 oncogenes.
AB  - The GLI transcription factors mediate the hedgehog signal in development and
      carcinogenesis. Basal cell carcinoma can be caused by overexpression of either
      GLI1 or GLI2. Though GLI1 and GLI2 have identical or very similar DNA binding
      specificities, some of their activities are overlapping, some are clearly
      distinct. We analyzed target gene specificities of GLI1 and constitutively active
      GLI2 (GLI2DeltaN) by global expression profiling in an inducible, well
      characterized HaCaT keratinocyte expression system. Four hundred fifty-six genes
      up- or downregulated at least twofold were identified. GLI target gene profiles
      correlated well with the biological activities of these transcription factors in
      hair follicles and basal cell carcinoma. Upregulation of largely overlapping sets
      of target genes was effected by both factors, repression occurred predominantly
      in response to GLI2. Also, significant quantitative differences in response to
      GLI1 and GLI2DeltaN were found for a small number of activated genes. Since we
      have not detected a putative processed GLI2 repressor, these results point to
      specific but indirect target gene repression by GLI2DeltaN via preferential
      activation of one or more negative regulators.

PMID- 16434165
TI  - Toward understanding MHC disease associations: partial resequencing of 46
      distinct HLA haplotypes.
AB  - We carried out a resequencing project that examined 552 kb of sequence from each
      of 46 individual HLA haplotypes representing a diversity of HLA allele types,
      generating nearly 27 Mb of fully phased genomic sequence. Haplotype blocks were
      defined extending from telomeric of HLA-F to centromeric of HLA-DP including in
      total 5186 MHC SNPs. To investigate basic questions about the evolutionary origin
      of common HLA haplotypes, and to obtain an estimate of rare variation in the MHC,
      we similarly examined two additional sets of samples. In 19 independent HLA-A1,
      B8, DR3 chromosomes, the most common HLA haplotype in Northern European
      Caucasians, variation was found at 11 SNP positions in the 3600-kb region from
      HLA-A to DR. Partial resequencing of 282 individuals in the gene-dense class III
      region identified significant variability beyond what could have been detected by
      linkage to common SNPs.

PMID- 16434166
TI  - Effect of whole-body 1800MHz GSM-like microwave exposure on testicular
      steroidogenesis and histology in mice.
AB  - The aim of our study was to evaluate the possible effects of whole-body 1800 MHz
      GSM-like microwave exposure on male reproduction. After repeated exposure of mice
      to microwaves at 0.018-0.023 W/kg whole-body specific energy absorption rate
      (SAR) an elevated serum testosterone level was measured, but no microwave
      exposure related histopathological alteration could be detected in the
      reproductive organs. The in vitro steroidogenic response of 48 h Leydig cell
      cultures obtained from exposed animals did not differ from the controls,
      suggesting that Leydig cells were not the primary targets of the applied
      microwave exposure or direct action of microwaves on Leydig cells was temporary
      only. In exposed animals the red blood cell count and volume of packed red cells
      were also increased. Further investigations are required to clarify the mechanism
      of action of the applied microwave exposure on male mice, as well as to establish
      the biological significance of the observed phenomena.

PMID- 16434167
TI  - Testicular dysfunction and antioxidative defense system of Swiss mice after
      chromic acid exposure.
AB  - Chromic acid (CrO(3)), a hexavalent compound of chromium (Cr) that is widely used
      in different industries, has been associated with reproductive abnormalities in
      male Swiss mice. The mechanism of male reproductive toxicity is not clear. Metal
      induced reactive oxygen species (ROS) may impair spermatogenesis or alter sperm
      morphology. Therefore, in the present study we investigated the induction of
      oxidative stress in the testes of mice over time (5th-8th weeks) after a single
      intraperitoneal dose (1mg/kg body weight) of CrO(3). Exposed animals showed
      significantly decreased sperm counts and markedly increased rates of sperm
      abnormality. Oxidative stress was measured in terms of malondialdehyde content,
      the activities of superoxide dismutase, peroxidase, and catalase, and non
      enzymatic antioxidants such as ascorbic acid. The significant changes in exposed
      groups relative to controls suggest that CrO(3) exposure suppressed antioxidant
      enzymes and ascorbic acid with a concomitant increase in the level of lipid
      peroxidation and H(2)O(2) to adversely affect testicular function.

PMID- 16434168
TI  - Immunohistochemical localization of the vesicular glutamate transporter VGLUT2 in
      the developing and adult mouse claustrum.
AB  - We studied the immunoreactive expression pattern for the vesicular glutamate
      transporter VGLUT2 in the embryonic, postnatal and adult mouse dorsal claustrum,
      at the light and electron microscopic levels. VGLUT2 immunoreactivity in the
      dorsal claustrum starts to be observed at E16.5, with a dramatic increase towards
      P0. At this age, abundant VGLUT2-immunoreactive axons and puncta are observed in
      all pallial regions, including the claustral complex. From the first postnatal
      week, VGLUT2 immunoreactivity declines in several telencephalic areas, including
      the pallium, but abundant VGLUT2-immunoreactive fine axons and puncta remain in
      the claustrum. Beginning at E18.5, VGLUT2 immunoreactivity within the claustrum
      shows a characteristic arrangement: a central part of the region is practically
      devoid of VGLUT2 immunoreactivity, and it is surrounded by plenty of
      immunoreactive axon terminals forming a shell around it. This core/shell
      arrangement of the VGLUT2 immunoreactivity resembles the complementary expression
      of parvalbumin and calretinin described in the mouse claustrum [Real, M.A.,
      Davila, J.C., Guirado, S., 2003. Expression of calcium-binding proteins in the
      mouse claustrum. J. Chem. Neuroanat. 25, 151-160]. We observed immunoreactive
      neuronal cell bodies as well in the dorsal claustrum, but only at P0. Electron
      microscopic analysis reveals that VGLUT2 immunoreactivity in the developing and
      adult dorsal claustrum consists predominantly of presynaptic boutons making
      asymmetric synaptic contacts. These VGLUT2-immunoreactive boutons are observed as
      early as E16.5 and may be related to thalamo-claustral incoming fibers.

PMID- 16434169
TI  - Analytic representation of volume flow as a function of geometry and pressure in
      a static physical model of the glottis.
AB  - A static physical model of the larynx (model M5) was used to obtain a large set
      of volume flows as a function of symmetric glottal geometry and transglottal
      pressure. The measurements cover ranges of these variables relevant to human
      phonation. A generalized equation was created to accurately estimate the glottal
      volume flow given specific glottal geometries and transglottal pressures. Both
      the data and the generalized formula give insights into the flow behavior for
      different glottal geometries, especially the contrast between convergent and
      divergent glottal angles at different glottal diameters. The generalized equation
      produced a fit to the entire M5 dataset (267 points) with an average accuracy of
      3.4%. The accuracy was about seven times better than that of the Ishizaka
      Flanagan approach to glottal flow and about four times better than that of a
      pressure coefficient approach. Thus, for synthesis purposes, the generalized
      equation presented here should provide more realistic glottal flows (based on
      steady flow conditions) as suitable inputs to the vocal tract, for given values
      of transglottal pressure and glottal geometry. Applications of the generalized
      formula to pulses generated by vocal fold motions typical of those produced by
      the Ishizaka-Flanagan coupled-oscillator model and the more recent body-cover
      model of Story and Titze are also included.

PMID- 16434170
TI  - Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of
      platelets in the liver and the ensuing anaphylaxis-like shock in mice.
AB  - Intravenous injection of Klebsiella O3 lipopolysaccharide (LPS) into BALB/c mice
      induces an anaphylaxis-like shock within minutes. Using 5-hydroxytryptamine as a
      marker for platelets, we previously suggested that a rapid platelet accumulation
      in the liver and lung precedes the shock, and that a complement-dependent
      platelet-degradation is involved in the shock. Here, we examined (i) the effect
      of platelet-depletion (using an anti-platelet monoclonal antibody) on the shock
      and (ii) the contribution of macrophages to the platelet-accumulation in those
      organs. LPS-induced platelet-accumulations in the liver and lung were confirmed
      by immunostaining. In platelet-depleted mice, the shock was largely prevented.
      The number of F4/80-positive macrophages was much greater in liver than in lung,
      and the hepatic macrophages were largely lost in mice given clodronate
      encapsulated liposomes. In mice treated with such liposomes, both the LPS-induced
      accumulation of platelets in the liver (but not in the lung) and the shock were
      largely prevented, and repopulation of hepatic macrophages restored these LPS
      induced responses. These results suggest that (i) platelets are indeed involved
      in the shock, (ii) Kupffer cells mediate the hepatic platelet accumulation, and
      (iii) preventing this hepatic accumulation can largely prevent rapid shock being
      induced by LPS (at the dose used here).

PMID- 16434171
TI  - [Prenatal urinary tract dilation: postnatal diagnostic workup].

PMID- 16434172
TI  - [Macroamylasemia: one pediatric case].
AB  - We report a case of macroamylasemia in an 11-year-old boy. We compare our
      clinical and paraclinical data with those described in pediatric literature.
      Macroamylase resulted in a complex of amylase and immuglobulin. Its fortuitous
      detection did not reveal, up to now, any associated pathology, in particular any
      autoimmune disorders or celiac disease. Identification of this biochemical
      abnormality is essential in order to avoid invasive investigations and/or
      unnecessary therapies.

PMID- 16434173
TI  - Bullous dermatosis associated with gemcitabine therapy for non-small-cell lung
      carcinoma.
AB  - Gemcitabine considered is to be a well-tolerated cytostatic drug with little
      known side effects. Cutaneous reactions are well known but still rarely reported.
      We report the case of a 75-year-old man with stage IV non-small-cell lung
      carcinoma treated with combination of gemcitabine 1000 mg/m2 and cisplatin 75
      mg/m2 repeated every 28 days, who developed bilateral cutaneous bullous lesions
      of lower limbs following gemcitabine administration. Histopathologic examination
      did not show any toxidermy aspect and there was not any sign of immunoglobulin
      deposit in direct immunofluorescence test. Chemotherapy was stopped and lesions
      disappeared without any treatment. Even delayed with regard to gemcitabine
      administration, the causal relationship of gemcitabine treatment with skin
      reaction is possible according to the Naranjo probability scale. Pathologists
      should be aware of this kind of side effect in managing chemotherapy drugs and
      report any dermatologic reactions in order to identify the cause of toxicity and
      avoid a misdiagnosis.

PMID- 16434174
TI  - Inhaled steroids improve quality of life in patients with steady-state
      bronchiectasis.
AB  - BACKGROUND: The effects of inhaled steroids upon the quality of life of patients
      with bronchiectasis remain unknown. STUDY OBJECTIVE: To analyze the effect of
      inhaled fluticasone propionate (FP) for 6 months upon the clinical, functional,
      microbiological and outcome parameters of patients with steady-state
      bronchiectasis not due to cystic fibrosis, and its repercussions for patient
      health-related quality of life (HRQoL). DESIGN: Prospective, randomized, double
      blind (for effective doses) study. PATIENTS AND INTERVENTIONS: The diagnosis of
      bronchiectasis was made by high-resolution computed tomography. Ninety-three
      patients (mean age: 68.5 [8.4]) were randomized to receive 250 microg bid, 500
      microg bid or no treatment with inhaled FP for 6 months. Data were collected at
      baseline and at 1, 3 and 6 months after the start of treatment. HRQoL was
      assessed using the validated Spanish version of the St. George's Respiratory
      Questionnaire. RESULTS: The group administered FP 1000 microg daily showed
      significant improvement in dyspnea (1.03 [2.1]-1.24 [2.2] points; P = 0.01-0.04),
      sputum production (P = 0.001), days without cough (P = 0.02) and short-acting
      beta-2 agonists used (P = 0.01) from the first month of treatment, with no
      changes in pulmonary function, number or severity of exacerbations, or
      microbiological profile of the sputum. As a result, an improvement in HRQoL was
      seen in this group after 3 months of treatment (45.4 [14.2] vs. 40.5 [13.9]; P =
      0.01). CONCLUSIONS: Inhalatory FP 500 microg bid is effective from the first
      month of treatment for controlling the symptoms of patients with steady-state
      bronchiectasis-thus ensuring a significant improvement in HRQoL.

PMID- 16434175
TI  - Utilization of pulverized fuel ash in Malta.
AB  - In Malta all of the waste produced is mixed and deposited at various sites around
      the island. None of these sites were purpose built, and all of the waste is above
      groundwater level. The landfills are not engineered and do not contain any
      measures to collect leachate and gases emanating from the disposal sites. Another
      waste, which is disposed of in landfills, is pulverized fuel ash (PFA), which is
      a by-product of coal combustion by the power station. This has been disposed of
      in landfill, because its use has been precluded due to the radioactivity of the
      ashes. The aim of this study was to analyze the chemical composition of the
      pulverized fuel ash and to attempt to utilize it as a cement replacement in
      normal concrete mixes in the construction industry. The levels of radiation
      emitted from the ashes were measured by gamma spectrometry. The results of this
      study revealed that although at early ages cement replacement by PFA resulted in
      a reduction in compressive strength (P=0), when compared to the reference
      concrete at later ages the strengths measured on concrete cores were comparable
      to the reference concrete (P>0.05). The utilization of PFA up to 20% cement
      replacement in concrete did not raise the radioactivity of the concrete. In
      conclusion, utilization of PFA in the construction industry would be a better way
      of disposing of the ashes rather than controlling the leachate and any
      radioactivity emitted by the landfilled ashes.

PMID- 16434176
TI  - Multiplexed measurement of serum antibodies using an array biosensor.
AB  - The array biosensor provides the capability for simultaneously measuring titers
      of antibody against multiple antigens. Human antibodies against four different
      targets, tetanus toxin, diphtheria toxin, staphylococcal enterotoxin B (SEB) and
      hepatitis B, were measured simultaneously in sera from eight different donors in
      a single assay and titers were determined. The assays could measure amounts of
      bound antibody as low as approximately 100 fg. Each individual serum exhibited a
      different pattern of reactivity against the four target antigens. Applications of
      this biosensor capability include monitoring for exposure to pathogens and for
      efficacy of vaccination.

PMID- 16434177
TI  - Metallic oxide CdIn2O4 films for the label free electrochemical detection of DNA
      hybridization.
AB  - DNA functionalised semiconductor metallic oxide electrodes have been developed
      for the direct electrochemical detection of DNA hybridization, without labelling
      or the introduction of a redox couple. Conductive CdIn(2)O(4) thin films with
      controlled properties were deposited on glass substrates using an aerosol
      pyrolysis technique. The films exhibit a polycrystalline microstructure with a
      surface roughness of 1.5 nm (r.m.s.) and an electrical resistivity ranging
      between 1 and 3 x 10(-3) Omega cm. These electrodes were functionalised using
      hydroxylation and silanisation steps, to allow the binding of DNA probe sequences
      (20 bases). The electrical detection of DNA hybridization with complementary
      sequences has been performed using electrochemical impedance spectrometry (EIS)
      measuring the variation of impedance before and after hybridization. Two set-ups
      were used, a standard set-up including three electrodes and a set-up including
      two symmetrical electrodes. In both configurations, a significant increase of the
      impedance modulus, more particularly of the real part of the impedance (160-225%
      according to the electrochemical cell used) has been obtained over a frequency
      range of 10-10(5)Hz. DNA hybridization has also been systematically confirmed
      using the fluorescence spectrometry. This study emphasizes the high sensitivity
      of the CdIn(2)O(4) as a working electrode for the detection of biological events
      occurring at the electrode surface.

PMID- 16434178
TI  - Anesthetic management for cesarean section in moyamoya disease: a report of five
      consecutive cases and a mini-review.
AB  - We report five consecutive cases of neuraxial anesthesia for cesarean section in
      women with moyamoya disease. Either epidural or combined spinal-epidural
      anesthesia was provided, with adequate sedation using intravenous diazepam and/or
      opioid(s). Hemodynamic stability and normocapnia were well maintained, except in
      one patient who exhibited transient hypertension and hypocapnia due to anxiety.
      None of the parturients suffered from neurological deficit in the intra- or
      postoperative period, although one patient complained of numbness in her fingers
      at the end of surgery, but she was not hypotensive or hypocapneic. The neonates
      were all in good health. The literature is reviewed on the anesthetic management
      for cesarean section in patients with moyamoya disease.

PMID- 16434179
TI  - Anesthetic management for cesarean delivery in a woman with Gilles de la
      Tourette's syndrome.
AB  - Gilles de la Tourette's syndrome is a chronic neuropsychiatric disorder with an
      early childhood onset featuring mainly motor and vocal tics. We present the
      anesthetic management for cesarean delivery of a 21-year-old pregnant woman with
      Tourette's syndrome. She had shrugging of the shoulders and sudden, jerky,
      repetitive, irregular movements of the hands. General anesthesia was given for
      cesarean delivery. A live male infant weighing 3130 g was delivered. Her
      perioperative course was uneventful. No complication was observed. The patient
      and baby were discharged on the 4th postoperative day. It was decided to
      prescribe haloperidol 5 mg per day after lactation. Anesthesiologists should
      remember that there are special considerations when managing anesthesia in
      patients with Tourette's syndrome. The motor tics may lead to technical
      difficulty in performing regional anesthesia and surgery. Therefore general
      anesthesia may be appropriate in order to prevent agitation or involuntary
      movements. If patient movement and agitation can be controlled by sedation,
      regional block may be attempted. Drugs such as metoclopramide, ondansetron,
      midazolam and opioids may be used safely for anesthesia in Tourette's syndrome.

PMID- 16434180
TI  - Labor epidural placement in a woman with a cervical spinal cord stimulator.
AB  - A 37-year-old female, gravida 1 para 0, in active labor at term, with a cervical
      spinal cord stimulator in situ, presented for epidural analgesia for labor. She
      had received the cervical spinal cord stimulator some 30 months before, to treat
      chronic regional pain syndrome I. She was taking no medication, and was thin but
      otherwise healthy. The cervical spinal cord stimulator electrodes entered the C7
      T1 interspace, and their end was in the epidural space at the C3 level. The
      electrodes were fixed to a cervical spinous process, crossed the midline high in
      the back and then went down the left side of her back parallel to her spine to
      the generator, which was in her buttock. The electrode cable could be felt high
      on the left side of her back, but not in her lumbar region. After consultation,
      it was felt safe and reasonable to proceed with labor epidural anesthesia. The
      procedure took place with the patient sitting, using a standard reusable 17-gauge
      Tuohy needle. Subsequent analgesia was acceptable. The patient also observed
      about 20 min after receiving the epidural medication that suddenly she could move
      her right hand more easily and that it felt warm. Her labor and delivery
      proceeded uneventfully. The spinal cord stimulator continued to function well
      throughout the entire process. She noticed that the feeling in her right hand
      returned to baseline after the delivery.

PMID- 16434181
TI  - Practical management of the parturient with congenital heart disease.
AB  - Cardiac disease is becoming more common in women presenting for maternity care
      and is a major cause of maternal mortality in the UK. We present a review of the
      management of parturients with congenital heart disease, focusing on practical
      aspects and the problems that may be expected.

PMID- 16434182
TI  - Informed consent for labor epidurals: a survey of Society for Obstetric
      Anesthesia and Perinatology anesthesiologists from the United States.
AB  - BACKGROUND: Ethicists agree that informed consent is a process rather than just
      simply the signing of a form. It should provide the patient with needed
      information and understanding to authorize a procedure. Essential elements of
      informed consent for women requesting labor epidurals include a description of
      the procedure, the risks and benefits, and alternative treatments for analgesia
      including the associated risks and benefits. The purpose of this pilot study was
      to determine practices and opinions of obstetric anesthesiologists regarding
      informed consent for parturients. METHODS: Questionnaires were sent to 885
      anesthesiologists who were members of the Society of Obstetric Anesthesia and
      Perinatology based in United States institutions in 2002. RESULTS: Of the 885
      questionnaires sent, 448 (51%) were returned with 47% from academic and 47% from
      private practice institutions. Forty-six percent worked as part of an obstetric
      anesthesia team; 51% worked in centers where there were >3000 deliveries/year.
      Sixty-eight percent suggested that "parturients in active labor are able to give
      informed consent for labor epidural analgesia." Thirteen percent recommend
      antenatal anesthesia consults for parturients inquiring about labor epidurals and
      41% participated in childbirth classes. Responses did not differ significantly
      between physicians in academic vs. private practice. More obstetric team
      practices than non-team practices participated in childbirth education (54% vs.
      30%, P < 0.0001). CONCLUSION: Despite the painful, stressful circumstances
      confronted by parturients, many respondents (76% in academic, 64% in private
      practice) thought that women in active labor are able to give informed consent.

PMID- 16434183
TI  - Impact of walking epidural analgesia on obstetric outcome of nulliparous women in
      spontaneous labour.
AB  - BACKGROUND: To explore the effects of walking epidural analgesia on obstetric and
      neonatal outcomes, we performed a case-control study. METHOD: Each nulliparous
      woman receiving walking epidural analgesia using 0.0625% bupivacaine (n = 44) was
      matched to two nulliparous historical controls receiving 0.125% or 0.25%
      bupivacaine (n = 88 each) for epidural analgesia while recumbent. RESULTS:
      Maternal and obstetric parameters, fetal status and presentation, and oxytocin
      use were comparable among groups. Those receiving walking epidural analgesia
      walked for a mean of 60 min (range: 20-75 min). In the control groups the mean
      total durations of labour were shorter (58 min in the 0.125% group and 99 min in
      the 0.25% group, P < 0.05). Significantly fewer walking epidural analgesia cases
      than controls required instrumental vaginal delivery (P < 0.05). No other
      differences in obstetric or fetal outcome were observed and no mother fell or
      stumbled while walking. CONCLUSION: Although it was associated with a prolonged
      first stage of labour, walking epidural analgesia appeared safe for nulliparous
      women and their babies.

PMID- 16434184
TI  - Protein aggregation and amyloidosis: confusion of the kinds?
AB  - Recent years have witnessed major advances in our understanding of the structural
      basis of protein aggregation on several fronts. Firstly, high-resolution
      structural information that remained elusive for many years was provided by a
      series of studies of amyloid fibers using NMR, X-ray crystallography and electron
      microscopy, thereby confirming earlier models based on lower resolution
      observations. Secondly, studies of the sequence determinants of protein
      aggregation culminated in the development of computer algorithms that predict
      aggregation-prone sequences with good accuracy, allowing the design of mutations
      that reduce aggregation. Thirdly, based on the first results from such
      predictions and on statistical analysis of naturally occurring aggregating
      sequences, a picture is emerging in which aggregation-prone sequences are capped
      by gatekeeper residues that oppose aggregation. In addition to their aggregation
      opposing function, it seems that gatekeeper residues are also important in
      determining chaperone selectivity for strongly aggregating regions. Finally,
      recent computational and experimental work shows that preventing aggregation does
      not necessarily mean that amyloid formation is prevented and vice versa. Thus,
      although aggregation and amyloidosis correlate to a certain extent, they are
      different processes and should be treated as such.

PMID- 16434185
TI  - Argonaute and RNA--getting into the groove.
AB  - RNAi has made an enormous impact on biology in a very short period of time. It
      became an extraordinarily useful and simple tool for gene silencing, even as its
      fascinating mechanism was gradually unraveling. Understanding the mechanism of
      RNAi-related pathways, including both transcriptional and posttranscriptional
      gene silencing and even processes such as DNA elimination in Tetrahymena, have
      benefited from an incredible marriage of genetics, biochemistry, molecular
      biology, bioinformatics and finally structural biology. Structural biology played
      a key role in deciphering the role that a central player--the Argonaute protein-
      has in all RNAi processes.

PMID- 16434186
TI  - Mutational analysis of PDGFR-RAS/MAPK pathway activation in childhood
      medulloblastoma.
AB  - Aberrant signalling via platelet derived growth factor receptors (PDGFRs) and the
      RAS/MAPK pathway has been implicated in the development of medulloblastoma, the
      most common malignant brain tumour in childhood. To determine whether genetic
      mechanisms play a role in the activation of PDGFR-RAS/MAPK signalling in
      medulloblastoma, we performed a direct sequence analysis of the established
      mutational "hotspots" of known targets of activating mutations within the pathway
      (PDGFRA, NRAS, KRAS, HRAS and BRAF) and PDFRFB, in a cohort of 28 primary
      tumours. A synonymous sequence variation in PDGFRA (CCG to CCA; PRO 567 PRO) was
      detected in two cases (approximately 7%), but not in 150 normal chromosomes
      assessed, suggesting that the PDGFRA locus may be associated with medulloblastoma
      development in certain cases. No evidence for oncogenic mutations affecting NRAS,
      KRAS, HRAS, BRAF or PDFRFB was found in any case. These data demonstrate that
      activating mutations in established mutational hotspots within the PDGFR-RAS/MAPK
      pathway are rare events in medulloblastoma development, and suggest that
      alternative mechanisms are responsible for RAS/MAPK pathway activation in this
      disease.

PMID- 16434187
TI  - Risk-reducing surgery in women with familial susceptibility for breast and/or
      ovarian cancer.
AB  - This multicentre study examined uptake of bilateral risk-reducing mastectomy
      (BRRM) and bilateral risk-reducing oophorectomy (BRRO) in women at increased risk
      for breast and/or ovarian cancer who had attended a familial cancer clinic (FCC)
      between January 1999 and June 2000. Eligible women (N=396), were mailed a
      questionnaire assessing: BRRM and BRRO details; risk perception; and anxiety.
      Family history, genetic testing and risk assessment were abstracted from medical
      records. Surgery was cross-tabulated with demographics, risk perception and
      anxiety with either Fisher's exact test or the exact form of the Mantel-Haenszel
      test (for ordinal factors) used to investigate for associations. Ordinal logistic
      regression was used with continuous-scale covariates. In total, 130 women were
      lost to follow-up leaving 266; of these 182 (68.4%) responded. Mean follow-up
      time was 3.73 years. The BRRM rate was 4.4%; with no difference found between
      moderate and high-risk groups. BRRM was associated with increasing numbers of
      affected relatives (P=0.025). BRRO was undertaken by 17.3%, more commonly in
      women older than 40 years of age (P=0.023) and with a BRCA1/2 mutation (P=0.017).
      Women who underwent BRRM (P=0.052) or BRRO (P<0.001) had a lower post-procedure
      risk perception than those who did not. During the timeframe of this study, risk
      reducing surgery was undertaken by a small percentage of Australian women at
      increased risk for breast and/or ovarian cancer who attended FCCs. Family cancer
      history and mutation status were associated with uptake.

PMID- 16434188
TI  - Malignant ascites: systematic review and guideline for treatment.
AB  - A guideline on the management of symptomatic malignant ascites by abdominal
      paracentesis, diuretics and peritoneovenous shunting, based on a systematic
      review of the literature is presented. Thirty-two relevant studies were
      identified. None were randomized control trials, one was a non-randomized open
      controlled trial, five were cohort studies or prospective uncontrolled trials, 26
      studies were non-analytic studies like case series. Although paracentesis,
      diuretics and shunting are commonly used procedures, the evidence is weak.
      Available data show good, although temporary effect of paracentesis on symptom
      relief. Fluid withdrawal speed and concurrent intravenous hydration is not
      sufficiently studied. Peritoneovenous shunts can control ascites in patients with
      malignant ascites, but have to be balanced by the potential risks of this
      procedure. The available data about diuretics in treatment of malignant ascites
      are controversial. The use of diuretics therefore should be considered in all
      patients, but has to be evaluated individually.

PMID- 16434189
TI  - Antioxidant activity of novel chitin derivative.
AB  - Novel water-soluble chitin derivative was prepared by chemical modification to
      evaluate antioxidant activities by free radical scavenging potential using
      electron spin resonance spin trapping technique. Aminoethyl-chitin (AEC)
      exhibited free radical scavenging activities against 1,1-diphenyl-2
      picrylhydrazyl (DPPH), hydroxyl, superoxide, and peroxyl radicals. AEC quenched
      DPPH and peroxyl radical over 55% and 59% at 4mg/mL, and also suppressed
      superoixde radical over 58% at 2mg/mL. Especially, AEC was more active against
      hydroxyl radical, and scavenging ratio was 92.2% at 0.12mg/mL. These results
      suggested that free amino group in the -CH(2)CH(2)NH(2) plays an important role
      in the free radical scavenging activity. In addition, cytotoxic effect of AEC was
      assessed using human lung fibroblast (MRC-5) cell line, and AEC showed less toxic
      against MRC-5.

PMID- 16434190
TI  - Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.
AB  - Miltirone analogues were synthesized and evaluated for inhibitory activity
      against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25
      inhibitory activity, and several exhibited higher selectivity for Cdc25 than for
      PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against
      the tumor cell lines A549 and HCT-116, producing IC(50) values in the micromolar
      range.

PMID- 16434191
TI  - A novel ketone derivative of artemisinin biotransformed by Streptomyces griseus
      ATCC 13273.
AB  - A novel ketone derivative of artemisinin, artemisitone-9, was produced by the
      biotransformation of cultured Streptomyces griseus ATCC 13273. The structure of
      the ketone product was fully elucidated by various spectroscopic techniques, and
      the mechanism of generating such novel metabolite is also discussed.

PMID- 16434192
TI  - Fluorescent non-imidazole histamine H3 receptor ligands with nanomolar
      affinities.
AB  - Omega-piperidinoalkanamine derivatives with fluorescent moieties (2-cyanoisoindol
      1-yl, 7-nitrobenzofurazan-4-yl) have been synthesized starting from piperidine in
      three steps. The compounds display moderate to good histamine hH(3) receptor
      affinities with K(i) values ranging from 178 to 11nM. The new compounds may act
      as tools for identification and understanding of the binding site on the
      histamine H(3) receptor.

PMID- 16434193
TI  - Synthesis and antifungal activity of 6-hydroxycinnolines.
AB  - 6-Hydroxycinnolines 2 and cyclohexa-2,5-diene-1,4-dione derivatives 6 were
      synthesized and tested for in vitro antifungal activity against Candida and
      Aspergillus species. 6-Hydroxycinnolines 2 showed, in general, more potent
      antifungal activity against Candida species than the other cyclohexa-2,5-diene
      1,4-diones. The results suggest that 6-hydroxycinnolines would be potent
      antifungal agents.

PMID- 16434195
TI  - Aminobenzisoxazoles with biaryl P4 moieties as potent, selective, and orally
      bioavailable factor Xa inhibitors.
AB  - We have previously reported on a series of aminobenzisoxazoles as potent,
      selective, and orally bioavailable factor Xa inhibitors, which culminated in the
      discovery of razaxaban. Herein, we describe another approach to improve factor Xa
      inhibitory potency and pharmacokinetic profile by incorporating basic and water
      soluble functionalities on the terminal ring of the P4 biaryl group found in our
      earlier Xa inhibitors. This approach resulted in a series of potent, selective,
      and orally bioavailable factor Xa inhibitors.

PMID- 16434194
TI  - Synthesis and evaluation of febrifugine analogues as potential antimalarial
      agents.
AB  - Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active
      component against Plasmodium falciparum. Strong liver toxicity has precluded
      febrifugine as a potential clinical drug. In this study novel febrifugine
      analogues were designed and synthesized. Lower toxicity was achieved by reducing
      or eliminating the tendency of forming chemically reactive and toxic
      intermediates and metabolites. Synthesized compounds were evaluated in vitro
      against chloroquine sensitive (D6) and chloroquine resistant (W2) P. falciparum
      strains for efficacy and in freshly isolated rat hepatocytes for potential
      cytotoxicity. The IC(50)'s of the best compounds were superior to their parent
      compound febrifugine. Noticeably, these compounds were also over 100 times less
      toxic than febrifugine. These compounds, as well as the underlying design
      rationale, may find usefulness in the discovery and development of new
      antimalarial drugs.

PMID- 16434196
TI  - Froude number fractions to increase walking pattern dynamic similarities:
      application to plantar pressure study in healthy subjects.
AB  - The purpose of this study was to determine if using similar walking velocities
      obtained from fractions of the Froude number (N(Fr)) and leg length can lead to
      kinematic and kinetic similarities and lower variability. Fifteen male subjects
      walked on a treadmill at 0.83 (VS(1)) and 1.16ms(-1) (VS(2)) and then at two
      similar velocities (V(Sim27) and V(Sim37)) determined from two fractions of the
      N(Fr) (0.27 and 0.37) so that the average group velocity remained unchanged in
      both conditions (VS(1)=V (Sim27)andVS(2)=V (Sim37)). N(Fr) can theoretically be
      used to determine walking velocities proportional to leg lengths and to establish
      dynamic similarities between subjects. This study represents the first attempt at
      using this approach to examine plantar pressure. The ankle and knee joint angles
      were studied in the sagittal plane and the plantar pressure distribution was
      assessed with an in-shoe measurement device. The similarity ratios were computed
      from anthropometric parameters and plantar pressure peaks. Dynamically similar
      conditions caused a 25% reduction in leg joint angles variation and a 10%
      significant decrease in dimensionless pressure peak variability on average of
      five footprint locations. It also lead to heel and under-midfoot pressure peaks
      proportional to body mass and to an increase in the number of under-forefoot
      plantar pressure peaks proportional to body mass and/or leg length. The use of
      walking velocities derived from N(Fr) allows kinematic and plantar pressure
      similarities between subjects to be observed and leads to a lower inter-subject
      variability. In-shoe pressure measurements have proven to be valuable for the
      understanding of lower extremity function. Set walking velocities used for
      clinical assessment mask the effects of body size and individual gait mechanics.
      The anthropometric scaling of walking velocities (fraction of N(Fr)) should
      improve identification of unique walking strategies and pathological foot
      functions.

PMID- 16434197
TI  - Facilitation and reciprocal inhibition by imagining thumb abduction.
AB  - It is well known that motor evoked potentials (MEPs) elicited by transcranial
      magnetic stimulation (TMS) of the motor cortex are facilitated by voluntary
      muscle contraction. We evaluated the effects of imagination of movements on MEP
      latencies of agonist and antagonist muscles in the hand using TMS. Twenty-two
      healthy volunteers were studied. TMS delivered at rest and while imagining tonic
      abduction of the right thumb. MEPs were recorded in response to magnetic
      stimulation over the scalp and cervical spine (C7-T1), and central motor
      conduction times (CMCT) were calculated. MEPs were recorded from right abductor
      pollicis brevis muscle (APB) and adductor pollicis muscle (AP) simultaneously.
      Imagination of abduction resulted in a shortened latency of MEPs in the APB
      muscle, and a prolonged latency in the AP muscle. But the imagination caused no
      significant change in the latency of MEPs elicited by stimulation over the
      cervical spine. The changes of the CMCT may account for these latency changes
      with imagination of movement. These findings indicate that imagination of thumb
      abduction facilitates motoneurons of agonist muscle and has an inhibitory effect
      on those of antagonist muscle (reciprocal inhibition).

PMID- 16434198
TI  - Design, synthesis, and bioactivity of simplified paclitaxel analogs based on the
      T-Taxol bioactive conformation.
AB  - A strategy for the design and synthesis of simplified paclitaxel analogs based on
      the T-Taxol conformation is presented. The resulting compounds have both
      cytotoxic and tubulin polymerization activities, although less so than those of
      paclitaxel itself.

PMID- 16434199
TI  - Carbonyl- and sulfur-containing analogs of suberoylanilide hydroxamic acid:
      Potent inhibition of histone deacetylases.
AB  - Suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase, is
      used in clinical trials for a variety of advanced cancers. Twelve new analogs of
      SAHA were synthesized and tested as in vitro inhibitors of isolated histone
      deacetylases (HDACS) and in vivo inhibitors of interferon regulated
      transcriptional responses (a marker for HDAC activity). The analogs containing an
      alpha-mercaptoketone or an alpha-thioacetoxyketone were more potent than SAHA in
      both assays.

PMID- 16434200
TI  - Synthesis and binding affinities of methylvesamicol analogs for the acetylcholine
      transporter and sigma receptor.
AB  - We synthesized methylvesamicol analogs 13-16 and investigated the binding
      characteristics of 2-[4-phenylpiperidino]cyclohexanol (vesamicol) and
      methylvesamicol analogs 13-16, with a methyl group introduced into the 4
      phenylpiperidine moiety, to sigma receptors (sigma-1, sigma-2) and to vesicular
      acetylcholine transporters (VAChT) in membranes of the rat brain and liver. In
      competitive inhibition studies, (-)-o-methylvesamicol [(-)-OMV] (13) (Ki=6.7 nM),
      as well as (-)-vesamicol (Ki=4.4 nM), had a high affinity for VAChT. (+)-p
      Methylvesamicol [(+)-PMV] (16) (Ki=3.0 nM), as well as SA4503 (Ki=4.4 nM),
      reported as a sigma-1 mapping agent for positron emission tomography (PET), had a
      high affinity for the sigma-1 receptor. The binding affinity of (+)-PMV (16) for
      the sigma-1 receptor (Ki=3.0 nM) was about 13 times higher than that for the
      sigma-2 (sigma-2) receptor (Ki=40.7 nM). (+)-PMV (16) (Ki=199 nM) had a much
      lower affinity for VAChT than SA4503 (Ki=50.2 nM) and haloperidol (Ki=41.4 nM).
      These results showed that the binding characteristics of (-)-OMV (13) to VAChT
      were similar to those of (-)-vesamicol and that (+)-PMV (16) bound to the sigma-1
      receptor with high affinity. In conclusion, (-)-OMV (13) and (+)-PMV (16), which
      had a suitable structure, with a methyl group for labeling with 11C, may become
      not only a new VAChT ligand and a new type of sigma receptor ligand,
      respectively, but may also become a new target compound of VAChT and the sigma-1
      receptor radioligand for PET, respectively.

PMID- 16434202
TI  - Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable
      melanin-concentrating hormone receptor 1 antagonists.
AB  - The optimization of the distance between two key pharmacophore features within
      our first hit compounds 1a and 2a led to the identification of a new class of
      potent non-peptidic antagonists for the MCH-R1, based around 4-amino-2
      cyclohexylaminoquinazolines. In particular, ATC0065 (2c), N2-[cis-4-([2-[4-Bromo
      2-(trifluoromethoxy)phenyl]ethyl]amino)cyclohexyl]-N4,N4-dimethylquinazoline-2,4
      diamine dihydrochloride, bound with high affinity to the MCH-R1 (IC50 value of 16
      nM) and showed good metabolic stability in liver microsomes from human and rat.

PMID- 16434201
TI  - Anticancer activities of novel chalcone and bis-chalcone derivatives.
AB  - A series of novel chalcones and bis-chalcones containing boronic acid moieties
      has been synthesized and evaluated for antitumor activity against the human
      breast cancer MDA-MB-231 (estrogen receptor-negative) and MCF7 (estrogen receptor
      positive) cell lines and against two normal breast epithelial cell lines, MCF-10A
      and MCF-12A. These molecules inhibited the growth of the human breast cancer cell
      lines at low micromolar to nanomolar concentrations, with five of them (1-4, 9)
      showing preferential inhibition of the human breast cancer cell lines.
      Furthermore, bis-chalcone 8 exhibited a more potent inhibition of colon cancer
      cells expressing wild-type p53 than of an isogenic cell line that was p53-null.

PMID- 16434203
TI  - Synthesis and SAR studies of a novel series of T-type calcium channel blockers.
AB  - For the novel, potent, and selective T-type Ca2+ channel blockers, a series of
      sulfonamido-containing 3,4-dihydroquinazoline derivatives were prepared and
      evaluated for their blocking actions on T- and N-type Ca2+ channels. Among them,
      9c (KYS05064, IC50 = 0.96 +/- 0.22 microM) was found to be as potent as
      Mibefradil and also showed the highest selectivity for T-type Ca2+ channel with
      no effect on N-type Ca2+ channel.

PMID- 16434205
TI  - Survival and quality of life after repair of acute type A aortic dissection in
      patients aged 75 years and older justify intervention.
AB  - OBJECTIVE: Controversy still exists about averting expenditure of health care
      resources on the growing elderly population. This study evaluates clinical
      outcome of patients aged 75 years and older operated upon for acute type A aortic
      dissection. METHODS: Between January 1990 and April 2004, of 247 patients
      undergoing emergency operation for acute type A aortic dissection at our
      Institution, 40 patients (16%) were aged 75 years and older (mean 78+/-3 years,
      range 75-88 years) and represent the study population. On admission, 9 (22.5%)
      had cardiogenic shock/hypotension, 20 (50%) cardiac tamponade, 14 (35%) kidney
      failure, 11 (27.5%) limb ischemia, 3 (7.5%) neurologic deficit, and 1 (2.5%)
      myocardial ischemia. Surgical procedures included isolated replacement of the
      ascending aorta in 34 patients (85%), associated with total root replacement in 5
      (12.5%), and with aortic valve replacement in 1 (2.5%). Eleven patients (27.5%)
      underwent aortic arch replacement (hemiarch: n=8, 20%; total arch: n=3, 7.5%).
      RESULTS: In-hospital mortality was 30% (12 patients). Mortality tended to be
      higher (8/21, 38% vs 4/19, 21%; p=NS) for patients presenting with any one of the
      following complications: tamponade, shock, brain and/or myocardial, renal, limb
      malperfusion. Actuarial survival at 1, 5, and 7 years was 93+/-5%, 80+/-8%, and
      80+/-8%, respectively, and freedom from reoperation 97+/-2%, 97+/-2%, and 97+/
      2%, respectively. Actuarial event-free rates were 94+/-3%, 90+/-5%, and 90+/-5%.
      Seventy-four percent of survivors are in NYHA FC I, and quality of life test
      (RAND SF-36) revealed a generalized perception of independency and well-being,
      comparable to an age-matched population. CONCLUSIONS: Overall results for
      emergency repair of acute type A aortic dissection in the elderly justify
      intervention, particularly in uncomplicated cases. Expeditious referral and
      intervention by lowering pre-operative dissection-related complications and
      comorbidities might help to improve results. Survivors show functional status and
      quality of life similar to contemporary individuals.

PMID- 16434204
TI  - Comparison of surgical results after pneumonectomy and sleeve lobectomy for non
      small cell lung cancer: trends over time and 20-year institutional experience.
AB  - OBJECTIVE: Sleeve lobectomy is a lung-saving procedure for central tumors for
      which the alternative is pneumonectomy. The purpose of this study was to report
      the clinical characteristics, operative results, survival, and late outcomes over
      20 years in patients who underwent sleeve lobectomy and pneumonectomy at our
      institution. METHODS: There were 62 patients who underwent sleeve lobectomy (SL
      group) and 110 who underwent pneumonectomy (PN group). Comparisons of the
      demographics, morbidity, and survivals between the groups were performed by
      unpaired t-test, chi(2)-test, and log-rank test. RESULTS: Patients who underwent
      a pneumonectomy showed a significantly advanced pathological stage, and a larger
      tumor size than those who received a sleeve lobectomy, whereas there were no
      significant differences in histology, ratio of combined resection and induction
      therapy, or total morbidity. There were three in-hospital deaths (4.8%) in the SL
      group and four (3.6%) in the PN group. Local relapse and distant recurrence
      incidence were similar between the two groups. The 5-year-survival rates of the
      SL and PN groups were 54% and 33%, respectively (p<0.0001). However, there were
      no differences in 5-year survivals in patients with pathological stage I/II (SL,
      59% vs PN, 63%) and those who received induction therapy (SL, 22% vs PN, 52%)
      between the groups. CONCLUSIONS: Both pneumonectomy and sleeve lobectomy were
      performed with an acceptable risk of operative mortality and satisfactory 5-year
      survival rate. The indication of pneumonectomy is aimed to perform a curative
      resection for locally advanced lung cancer, particularly after induction therapy
      that is otherwise unresectable, and the selected patients will likely benefit
      from a complete resection.

PMID- 16434206
TI  - The effect of skin surface warming during anesthesia preparation on preventing
      redistribution hypothermia in the early operative period of off-pump coronary
      artery bypass surgery.
AB  - OBJECTIVE: Redistribution hypothermia adversely affects hemodynamics and
      postoperative recovery in patients undergoing cardiac surgery. In off-pump
      coronary bypass surgery (OPCAB), maintaining the temperature is important because
      warming by cardiopulmonary bypass is omitted. Pre-warming studies reported
      earlier showing pre-warming as an effective means of preventing redistribution
      hypothermia was time consuming since it required at least 1-2h to pre-warm the
      patients before the surgery. Because pre-warming for such a long time is
      impractical in clinical practice, this study evaluated the efficacy of active
      warming during the preanesthetic period for the prevention of redistribution
      hypothermia in the early operative period of OPCAB. METHODS: After gaining the
      approval of Institutional Review Board and informed consent from the patients, 40
      patients undergoing OPCAB were divided into control and pre-warming groups. The
      patients in control group (n=20) were managed with warm mattresses and cotton
      blankets, whereas patients in pre-warming group (n=20) were actively warmed with
      a forced-air warming device before the induction of anesthesia. Hemodynamic
      variables and temperature were recorded before anesthesia (Tpre) and at 30 min
      intervals after anesthesia for 90 min (T30, T60, and T90). RESULTS: Active
      warming duration was 49.7+/-9.9 min. There were no statistically significant
      differences in skin temperature, core temperature and hemodynamic variables
      between the two groups at preinduction period except for mean arterial pressure
      and central venous pressure. The core temperature at T30, T60, and T90 was
      statistically higher in pre-warming group than that in control group. Core
      temperature of six (30%) and seven patients (35%) in control group was reduced
      below 35 degrees C at T60 and T90, respectively, whereas core temperature of only
      one patient (5%) in pre-warming group was reduced below 35 degrees C at T90
      (P=0.02). CONCLUSIONS: Active warming using forced air blanket before the
      induction of anesthesia reduced the incidence and degree of redistribution
      hypothermia in patients undergoing OPCAB. It is a simple method with reasonable
      cost, which does not delay the induction of anesthesia nor the surgery.

PMID- 16434208
TI  - The genetics of HNPCC: application to diagnosis and screening.
AB  - Hereditary nonpolyposis colorectal cancer syndrome (HNPCC; Lynch Syndrome) is the
      most common form of hereditary colorectal cancers. Predisposed individuals have
      increased lifetime risk of developing colorectal, endometrial and other cancers.
      The syndrome is primarily due to heterozygous germline mutations in one of the
      mismatch repair genes; mainly MLH1, MSH2, MSH6 and PMS2. The resulting mismatch
      repair deficiency leads to microsatellite instability which is the hallmark of
      tumors arising within this syndrome, as well as a variable proportion of sporadic
      tumors. Diagnostic guidelines and criteria for molecular testing of suspected
      families have been proposed and are continuously updated. However, not all
      families fulfilling these criteria show mutations in mismatch repair genes and/or
      microsatellite instability implicating other, as yet unknown, carcinogenic
      mechanisms and predisposition genes. This subset of tumors is the focus of
      current clinical and molecular research. This review addresses recent advances in
      the field of HNPCC research and their applications in the management of affected
      individuals and families.

PMID- 16434209
TI  - Variation in expression of gastric leptin according to differentiation and growth
      pattern in gastric adenocarcinoma.
AB  - Leptin is an adipocyte-derived hormone that regulates body fat stores and feeding
      behavior. The presence of leptin in stomach epithelium was recently demonstrated
      in the rat and humans, and gastric leptin has been linked to the control of meal
      size, local inflammatory responses, and paracrine and autocrine functions through
      leptin receptors in the stomach. We compared the expression patterns of leptin
      and of the long variant of the leptin receptor (Ob-Rb) between areas with non
      ulcerated mucosa and with hyperplastic polyps, adenoma, or adenocarcinoma to
      evaluate the expression relative to different disease states. Leptin and Ob-Rb
      were expressed in hyperplastic polyps, adenoma, and adenocarcinoma. In the
      gastric adenocarcinoma, leptin was expressed significantly less in the poorly
      differentiated and diffuse-type groups than in the well-differentiated and
      moderately differentiated groups or in the intestinal type. Based upon our
      findings, we suggest the possibility that leptin expression can have a
      pathophysiologic role about the differentiation or growth pattern of gastric
      adenocarcinoma. A further series of experiments is necessary to elucidate the
      pathophysiological role of leptin in the differentiation of gastric
      adenocarcinoma.

PMID- 16434210
TI  - Formation and stability of charged amino acid clusters and the role of chirality.
AB  - Amino acid clusters have been studied by several groups and most notably magic
      number clusters and chiral recognition have been reported. In this work, we have
      studied the formation of amino acid clusters by electrospray ionization (ESI) and
      their stability by high-energy collision-induced dissociation (CID). Appearance
      sizes were determined for multiply charged clusters where the charge is either
      due to protons or to sodium ions. Finally, we conclude that chiral selectivity
      plays an important role in cluster formation but seems to be of minor importance
      for the fragmentation of mixed clusters.

PMID- 16434211
TI  - Establishment of a yeast system that stably expresses human cytochrome P450
      reductase: application for the study of drug metabolism of cytochrome P450s in
      vitro.
AB  - Cytochrome P450s (CYPs) hold a balance in studying pharmacokinetics, toxico
      kinetics, drug metabolism, and drug-drug interactions, which require association
      with cytochrome P450 reductase (CPR) to achieve optimal activity. A novel system
      of Saccharomyces cerevisiae useful for expression studies of mammalian microsomal
      CYPs was established. Human CPR (hCPR) was co-expressed with human CYP3A4
      (hCYP3A4) in this system, and two expression plasmids pTpLC and pYeplac195-3A4
      containing the cDNA of hCPR and hCYP3A4 were constructed, respectively. The two
      plasmids were applied first and controlled by phosphoglycerate kinase (PGK)
      promoter. S. cerevisiae BWG1-7alpha transformed with the expression plasmids
      produced the respective proteins in the expected molecular sizes reactive with
      both anti-hCYP3A4 immunoglobulin (Ig) and anti-hCPR Ig. The activity of hCPR in
      yeast BWG-CPR was 443.2 nmol reduced cytochrome c/min/mg, which was about three
      times the CPR activity of the microsome prepared from the parental yeast. The
      protein amount of hCYP3A4 in BWG-CPR/3A4 was 35.53 pmol/mg, and the 6beta
      hydroxylation testosterone formation activity of hCYP3A4 expressed was 7.5
      nmol/min/nmol CYP, 30 times higher than the activity of hCYP3A4 expressed in the
      parental yeast, and almost two times the activity of hCYP3A4 from homologous
      human liver microsome. Meanwhile, BWG-CPR/3A4 retained 100 generations under
      nonselective culture conditions, indicating this yeast was a mitotically stable
      transformant. BWG-CPR was further tested daily by the PCR amplification of hCPR
      of yeast genome, Western blot analysis, and the activity assay of hCPR of yeast
      microsome. This special expression host for CYPs was validated to be stable and
      efficient for the expression of CYPs, applying as an effective selection model
      for the drug metabolism in vitro.

PMID- 16434212
TI  - Observations on the behavior of vitreous ice at approximately 82 and
      approximately 12 K.
AB  - In an attempt to determine why cooling with liquid helium actually proved
      disadvantageous in our electron cryotomography experiments, further tests were
      performed to explore the differences in vitreous ice at approximately 82 and
      approximately 12 K. Electron diffraction patterns showed clearly that the
      vitreous ice of interest in biological electron cryomicroscopy (i.e., plunge
      frozen, buffered protein solutions) does indeed collapse into a higher density
      phase when irradiated with as few as 2-3 e-/A2 at approximately 12 K. The high
      density phase spontaneously expanded back to a state resembling the original, low
      density phase over a period of hours at approximately 82 K. Movements of gold
      fiducials and changes in the lengths of tunnels drilled through the ice confirmed
      these phase changes, and also revealed gross changes in the concavity of the ice
      layer spanning circular holes in the carbon support. Brief warmup-cooldown cycles
      from approximately 12 to approximately 82 K and back, as would be required by the
      flip-flop cryorotation stage, did not induce a global phase change, but did allow
      certain local strains to relax. Several observations including the rates of
      tunnel collapse and the production of beam footprints suggested that the high
      density phase flows more readily in response to irradiation. Finally, the
      patterns of bubbling were different at the two temperatures. It is concluded that
      the collapse of vitreous ice at approximately 12 K around macromolecules is too
      rapid to account alone for the problematic loss of contrast seen, which must
      instead be due to secondary effects such as changes in the mobility of radiolytic
      fragments and water.

PMID- 16434213
TI  - Agonist and antagonist muscle activation during maximal and submaximal isokinetic
      fatigue tests of the knee extensors.
AB  - The purpose of this study was to examine the differences in electromyographic
      activity of agonist and antagonist knee musculature between a maximal and a
      submaximal isokinetic fatigue protocol. Fourteen healthy males (age: 24.3+/-2.5
      years) performed 25 maximal (MIFP) and 60 submaximal (SIFP) isokinetic concentric
      efforts of the knee extensors at 60 degrees s(-1), across a 90 degrees range of
      motion. The two protocols were performed a week apart. The EMG activity of vastus
      medialis (VM), vastus lateralis (VL) and biceps femoris (BF) were recorded using
      surface electrodes. The peak torque (PT) and average EMG (aEMG) were expressed as
      percentages of pre-fatigue maximal value. One-way analysis of variance indicated
      a significant (p<0.05) decline of PT during the maximal (45.7%) and submaximal
      (46.8%) protocols. During the maximal test, the VM and VL aEMG initially
      increased and then decreased. In contrast, VM and VL aEMG continuously increased
      during submaximal testing (p<0.05). The antagonist (BF) aEMG remained constant
      during maximal test but it increased significantly and then declined during the
      submaximal testing. The above results indicate that agonist and antagonist
      activity depends on the intensity of the selected isokinetic fatigue test.

PMID- 16434214
TI  - A method to produce evolving functional connectivity maps during the course of an
      fMRI experiment using wavelet-based time-varying Granger causality.
AB  - Functional magnetic resonance imaging (fMRI) is widely used to identify neural
      correlates of cognitive tasks. However, the analysis of functional connectivity
      is crucial to understanding neural dynamics. Although many studies of cerebral
      circuitry have revealed adaptative behavior, which can change during the course
      of the experiment, most of contemporary connectivity studies are based on
      correlational analysis or structural equations analysis, assuming a time
      invariant connectivity structure. In this paper, a novel method of continuous
      time-varying connectivity analysis is proposed, based on the wavelet expansion of
      functions and vector autoregressive model (wavelet dynamic vector autoregressive
      DVAR). The model also allows identification of the direction of information flow
      between brain areas, extending the Granger causality concept to locally
      stationary processes. Simulation results show a good performance of this approach
      even using short time intervals. The application of this new approach is
      illustrated with fMRI data from a simple AB motor task experiment.

PMID- 16434215
TI  - 76-space analysis of grey matter diffusivity: methods and applications.
AB  - Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) allow in vivo
      investigation of molecular motion of tissue water at a microscopic level in
      cerebral gray matter (GM) and white matter (WM). DWI/DTI measure of water
      diffusion has been proven to be invaluable for the study of many
      neurodegenerative diseases (e.g., Alzheimer's disease and Creutzfeldt-Jakob
      disease) that predominantly involve GM. Thus, quantitative analysis of GM
      diffusivity is of scientific interest and is promised to have a clinical impact
      on the investigation of normal brain aging and neuropathology. In this paper, we
      propose an automated framework for analysis of GM diffusivity in 76 standard
      anatomic subdivisions of gray matter to facilitate studies of neurodegenerative
      and other gray matter neurological diseases. The computational framework includes
      three enabling technologies: (1) automatic parcellation of structural MRI GM into
      76 precisely defined neuroanatomic subregions ("76-space"), (2) automated
      segmentation of GM, WM and CSF based on DTI data, and (3) automatic measurement
      of the average apparent diffusion coefficient (ADC) in each segmented GM
      subregion. We evaluate and validate this computational framework for 76-space GM
      diffusivity analysis using data from normal volunteers and from patients with
      Creutzfeldt-Jakob disease.

PMID- 16434216
TI  - Systematics of Chaetognatha under the light of molecular data, using duplicated
      ribosomal 18S DNA sequences.
AB  - While the phylogenetic position of Chaetognatha has became central to the
      question of early bilaterian evolution, the internal systematics of the phylum
      are still not clear. The phylogenetic relationships of the chaetognaths were
      investigated using newly obtained small subunit ribosomal RNA nuclear 18S (SSU
      rRNA) sequences from 16 species together with 3 sequences available in GenBank.
      As previously shown with the large subunit ribosomal RNA 28S gene, two classes of
      Chaetognatha SSU rRNA gene can be identified, suggesting a duplication of the
      whole ribosomal cluster; allowing the rooting of one class of genes by another in
      phylogenetic analyses. Maximum Parsimony, Maximum Likelihood and Bayesian
      analyses of the molecular data, and statistical tests showed (1) that there are
      three main monophyletic groups: Sagittidae/Krohnittidae,
      Spadellidae/Pterosagittidae, and Eukrohniidae/Heterokrohniidae, (2) that the
      group of Aphragmophora without Pterosagittidae (Sagittidae/Krohnittidae) is
      monophyletic, (3) the Spadellidae/Pterosagittidae and
      Eukrohniidae/Heterokrohniidae families are very likely clustered, (4) the
      Krohnittidae and Pterosagittidae groups should no longer be considered as
      families as they are included in other groups designated as families, (5)
      suborder Ctenodontina is not monophyletic and the Flabellodontina should no
      longer be considered as a suborder, and (6) the Syngonata/Chorismogonata and the
      Monophragmophora/Biphragmophora hypotheses are rejected. Such conclusions are
      considered in the light of morphological characters, several of which are shown
      to be prone to homoplasy.

PMID- 16434217
TI  - Effect of lamotrigine on sexual function in patients with epilepsy.
AB  - OBJECTIVE: To assess the course of sexual function in epilepsy patients treated
      with lamotrigine. MATERIAL AND METHODS: This open study included 141 patients
      treated with lamotrigine for a period of 8 months: 79 patients initiated
      treatment with lamotrigine monotherapy, and 62 were switched to lamotrigine
      because of lack of efficacy or adverse events to a previous antiepileptic drug
      (AED). Patients were assessed at baseline and after 4 and 8 months of treatment.
      In the baseline and final visits the Changes in Sexual Functioning Questionnaire
      (CSFQ) was applied. Analysis was performed in an intent-to-treat population.
      RESULTS: In women who started treatment with lamotrigine, a significant
      improvement was observed, both in total CSFQ score (increase of 5.39 +/- 6.95
      points; p < 0.05), and in the five dimensions of the scale (desire/frequency,
      desire/interest, pleasure, arousal/excitement and orgasm). In men, a significant
      improvement was only observed in the pleasure dimension. In the group of patients
      in whom a previous AED was substituted by lamotrigine, significant improvement
      was recorded in the dimensions of pleasure and orgasm in men and desire/frequency
      in women, whilst in women the desire/interest dimension showed a decrease.
      CONCLUSIONS: In this observational study, an improvement in sexual dysfunction
      was observed in association with lamotrigine. This could have been the result of
      improvement of the epilepsy, changes in quality of life, elimination of side
      effects from other AEDs, or a mood-stabilizing effect of lamotrigine.

PMID- 16434218
TI  - Bilateral convergent strabismus with exophthalmus (BCSE) in cattle: an overview
      of clinical signs and genetic traits.
AB  - Bilateral convergent strabismus with exophthalmus (BCSE) is a heritable eye
      defect prevalent in many cattle breeds and known worldwide. BCSE shows a
      progressive course often terminating in complete blindness. The onset of the
      defect can sometimes be slowly progressing (late in life) and, as the first signs
      of the defect are frequently not noticed prior to first breeding, prevention
      cannot be achieved only by exclusion of affected animals from the breeding
      program. This paper provides an overview of the clinical signs, histopathology
      and genetics of BCSE, its distribution in different cattle breeds and analyses
      the association between milk production traits and US Brown Swiss. There were
      different modes of inheritance proposed for BCSE, but although an autosomal
      dominant major gene is considered most likely in German Brown cattle, an
      association with milk production traits could not be found. Comparative molecular
      genetic approaches could help to characterize the responsible genes for this
      ocular disease in cattle.

PMID- 16434219
TI  - Bovine tuberculosis infection in wild mammals in the South-West region of
      England: a survey of prevalence and a semi-quantitative assessment of the
      relative risks to cattle.
AB  - In the United Kingdom, badgers are implicated in the transmission of
      Mycobacterium bovis to cattle, but little information is available on the
      potential role of other wild mammals. This paper presents the results of the
      largest systematic UK survey of M. bovis infection in other wild mammals. Mammal
      carcasses (4715) from throughout the South-West region of England were subjected
      to a systematic post mortem examination, microbiological culture of tissues and
      spoligotyping of isolates. Infection was confirmed in fox, stoat, polecat, common
      shrew, yellow-necked mouse, wood mouse, field vole, grey squirrel, roe deer, red
      deer, fallow deer and muntjac. Prevalence in deer may have been underestimated
      because the majority were incomplete carcasses, which reduced the likelihood of
      detecting infection. Infected cases were found in Wiltshire, Somerset, Devon and
      Cornwall, Gloucestershire and Herefordshire. Lesions were found in a high
      proportion of spoligotype-positive fallow, red and roe deer, and a single fox,
      stoat and muntjac. M. bovis spoligotypes occurred in a similar frequency of
      occurrence to that in cattle and badgers. Data on prevalence, pathology,
      abundance and ecology of wild mammals was integrated in a semi-quantitative risk
      assessment of the likelihood of transmission to cattle relative to badgers.
      Although most species presented a relatively low risk, higher values and
      uncertainty associated with muntjac, roe, red and in particular fallow deer,
      suggest they require further investigation. The results suggest that deer should
      be considered as potential, although probably localised, sources of infection for
      cattle.

PMID- 16434220
TI  - "You feel so hopeless": a qualitative study of GP management of acute back pain.
AB  - BACKGROUND: Biopsychosocial management of non-specific back pain in general
      practice has been problematical, with frequent inappropriate referral for imaging
      and secondary care interventions and lack of self-confidence in the ability to
      provide evidence-based care. AIMS: To examine GP attitudes to managing back pain
      as a biopsychosocial problem in order to inform future educational strategies
      that may improve practice. METHODS: Twenty-one GPs from separate practices within
      the Dorset and Somerset Strategic Health Authority area (UK) participated in
      telephone interviews leading to the development of vignettes to refine the
      theoretical framework for subsequent focus group interviews about evidence-based
      back pain management. Transcripts were analysed thematically. RESULTS: There were
      5 main emergent themes. These were generally negative and dominated by concerns
      about doctor-patient interaction. They included feelings of frustration,
      mismatches of perceptions in the doctor-patient relationship, problems in
      relation to time, challenges and discord between stakeholders in the process (for
      example, over sickness certification) and a lack of resources for education,
      awareness and local services to refer to. Psychosocial aspects of the actual care
      process were rarely raised. Participants favoured education that is
      multidisciplinary, in small group format and involves the participation of
      patients. CONCLUSIONS: This study illustrates the difficulties that GPs may have
      in applying the relevant evidence for the successful management of back pain. A
      desire to avoid conflict in the relationship with patients explained much of the
      problem of implementing evidence in general practice. This indicates a need for
      insightful educational strategies that involve active GP participation.

PMID- 16434221
TI  - Efficient simulation of magnetic resonance imaging with Bloch-Torrey equations
      using intra-voxel magnetization gradients.
AB  - The process of image formation in magnetic resonance imaging (MRI) can be
      simulated by means of an iterative solution of Bloch-Torrey equations. This is a
      useful accessory to analyze the influence of sample properties, sequence
      parameters and hardware specifications on the MRI signal. In this paper, a
      computer algorithm is presented which is based on calculating partial derivatives
      of the magnetization vector. This technique allows more efficient simulation than
      summation of isochromats (the latter being commonly employed for this purpose)
      and, as a result, the effect of diffusion on the MRI signal can be calculated
      iteratively. A detailed description of the algorithm is given, and its
      feasibility for different applications is studied. It is shown that the algorithm
      is most applicable to simulating the effect of field perturbations, i.e. intra
      voxel dephasing, but is also useful for other typical imaging experiments and the
      simulation of diffusion weighting.

PMID- 16434222
TI  - Systematic molecular dynamics searching in a lipid bilayer: application to the
      glycophorin A and oncogenic ErbB-2 transmembrane domains.
AB  - Molecular dynamics (MD) simulations of proteins in a lipid bilayer environment
      are usually undertaken with one or a few starting structures. Here we report a
      search protocol for systematically exploring the possible interactions in helical
      bundle transmembrane proteins, a frequently occurring structural motif. The
      search protocol correctly identifies the experimentally known structure of the
      dimeric human glycophorin A transmembrane domain as the lowest energy structure
      among five different models without any prior assumptions, whilst an identical in
      vacuo search fails to identify the correct structure. The lowest energy structure
      from the search in a lipid bilayer has a root mean square deviation of 1.1A to
      the experimental structure. We have applied the same search protocol to the
      unknown transmembrane structure of the oncogenic mutant ErbB-2 protein, a member
      of the family of epidermal growth factor receptors. Resulting structures show the
      role of glutamic acid hydrogen bonding and close helical packing. Water molecules
      may also play a key role in stabilisation of the transmembrane helix association.

PMID- 16434223
TI  - Drainage routes of bronchial blood flow in anaesthetized sheep.
AB  - The systemic circulation to the lung supplies the trachea and airway walls and
      may be important in the pathophysiology of asthma and pulmonary oedema. An
      understanding of the venous drainage pathways of this bronchial blood flow may be
      therapeutically important. The purpose of this study was to understand the normal
      drainage pathways in sheep. In seven anaesthetized, ventilated sheep we injected
      echo contrast agents into a systemic vein or into the bronchial artery while
      performing echocardiography to determine whether the drainage could be observed
      to the right heart and/or to the left heart. During transoesophageal echo (n=5)
      or heart surface echo (n=2), cephalic vein injection of <8 microm diameter
      gelatin microballoons promptly opacified the right but never the left-sided
      circulation. Air in agitated saline in the seven animals showed the same result.
      By contrast, injection into the bronchial artery promptly opacified the left
      atrium, left ventricle, and aorta but not the right-sided circulation in all
      seven microballoon injections and all but one of the air in agitated saline
      injections. The failure of the echo agents to pass through the pulmonary
      circulation may be related to sheep pulmonary intravascular macrophages or the
      surface forces on air bubbles of small size promoting collapse. The main
      conclusion is that there are bronchopulmonary anastomoses that connect the
      bronchial circulation to the pulmonary venous circulation connecting distal to
      the pulmonary capillaries. Any bronchial venous drainage to the right-sided
      circulation must have been below the detection level of the instruments and would
      in any case appear to be much less that the post-pulmonary capillary anastomoses
      noted. Pulmonary venous hypertension would be expected to have a direct effect on
      the bronchial circulation.

PMID- 16434225
TI  - Aplastic anemia in cats - clinicopathological features and associated disease
      conditions 1996-2004.
AB  - A retrospective study of 128 feline bone marrow reports identified 13 cases of
      aplastic anemia. Clinical diagnoses included chronic renal failure (n=5), feline
      leukemia virus infection (n=2), hyperthyroidism treated with methimazole (n=1)
      and idiopathic aplastic anemia (n=5). In some cats, starvation may play a role in
      the development of marrow aplasia. Some cats with aplastic anemia can have
      prolonged survival without resolution of the pancytopenia.

PMID- 16434224
TI  - Batch culture characterization and metabolic flux analysis of succinate-producing
      Escherichia coli strains.
AB  - This study presents an in-depth analysis of the anaerobic metabolic fluxes of
      various mutant strains of Escherichia coli overexpressing the Lactococcus lactis
      pyruvate carboxylase (PYC) for the production of succinate. Previously, a
      metabolic network design that includes an active glyoxylate pathway implemented
      in vivo increased succinate yield from glucose in an E. coli mutant to 1.6
      mol/mol under fully anaerobic conditions. The design consists of a dual succinate
      synthesis route, which diverts required quantities of NADH through the
      traditional fermentative pathway and maximizes the carbon converted to succinate
      by balancing the carbon flux through the fermentative pathway and the glyoxylate
      pathway (which has a lower NADH requirement). Mutant strains previously
      constructed during the development of high-yield succinate-producing strains were
      selected for further characterization to understand their metabolic response as a
      result of several genetic manipulations and to determine the significance of the
      fermentative and the glyoxylate pathways in the production of succinate. Measured
      fluxes obtained under batch cultivation conditions were used to estimate
      intracellular fluxes and identify critical branch point flux split ratios. The
      comparison of changes in branch point flux split ratios to the glyoxylate pathway
      and the fermentative pathway at the oxaloacetate (OAA) node as a result of
      different mutations revealed the sensitivity of succinate yield to these
      manipulations. The most favorable split ratio to obtain the highest succinate
      yield was the fractional partition of OAA to glyoxylate of 0.32 and 0.68 to the
      fermentative pathway obtained in strains SBS550MG (pHL413) and SBS990MG (pHL413).
      The succinate yields achieved in these two strains were 1.6 and 1.7 mol/mol,
      respectively. In addition, an active glyoxylate pathway in an ldhA, adhE, ack-pta
      mutant strain is shown to be responsible for the high succinate yields achieved
      anaerobically. Furthermore, in vitro activity measurements of seven crucial
      enzymes involved in the pathways studied and intracellular measurements of key
      intermediate metabolite pools provided additional insights on the physiological
      perturbations caused by these mutations. The characterization of these
      recombinant mutant strains in terms of flux distribution pattern, in vitro enzyme
      activity and intracellular metabolite pools provides useful information for the
      rational modification of metabolic fluxes to improve succinate production.

PMID- 16434226
TI  - Serological survey of vector-borne zoonotic pathogens in pet cats and cats from
      animal shelters and feral colonies.
AB  - Although cats and their arthropod parasites can sometimes be important sources of
      zoonotic diseases in humans, the extent of exposure among various cat populations
      to many potential zoonotic agents remains incompletely described. In this study,
      170 domestic cats living in private homes, feral cat colonies, and animal
      shelters from California and Wisconsin were evaluated by serology to determine
      the levels of exposure to a group of zoonotic vector-borne pathogens. Serological
      positive test results were observed in 17.2% of cats for Rickettsia rickettsii,
      14.9% for R akari, 4.9% for R typhi, 11.1% for R felis, and 14.7% for Bartonella
      henselae. Although vector-borne disease exposure has been documented previously
      in cats, the evaluation of multiple pathogens and diverse cat populations
      simultaneously performed here contributes to our understanding of feline exposure
      to these zoonotic pathogens.

PMID- 16434227
TI  - Cardiac state diagnosis using adaptive neuro-fuzzy technique.
AB  - Analysis of heart rate has become a popular noninvasive tool for assessing the
      activities of the autonomic nervous system (ANS). These signals may either
      contain indicators of a current disease or even warnings about impending
      diseases. However, to manually study and pinpoint heart abnormalities in
      voluminous data is strenuous and time consuming. Here, an adaptive neuro-fuzzy
      network is used to classify heart abnormalities in 10 different cardiac states
      and shown to be effective. The results indicate a high level of efficacy of tools
      used with an accuracy level of more than 94%.

PMID- 16434228
TI  - Raman spectroscopic investigation of acetylation of raw cotton.
AB  - Raman spectroscopy has been used to investigate raw cotton acetylation using
      acetic anhydride/4-dimethylaminopyridine (DMAP) catalyst blend without solvent.
      The Raman data further confirm successful acetylation as shown by FTIR that was
      demonstrated previously to be highly sensitive for determining the level of
      acetylation. However, the Raman peaks are much weaker than the FTIR bands.
      Nevertheless, the variations of the extent of acetylation estimated from both
      Raman and FTIR spectra with weight percent gain due to acetylation (WPG) were
      observed to follow the same pattern. The degrees of acetylation calculated from
      Raman data were also found to increase linearly with that calculated from the
      more sensitive FTIR technique. Raman technique is thus suitable for further
      development as an analytical tool for determining the acetylation level of
      natural cellulose fibres. Raman data have also shown that the acetylation
      reaction reduces the crystallinity of cotton.

PMID- 16434229
TI  - Electronic structures of acyl nitrites and nitrates.
AB  - The gas phase electronic structures of CM(3)C(O)ONO and CM(3)C(O)ONO(2) (M=H, Cl,
      F) are studied by photoelectron spectroscopy (PES) combined with the outer
      valence Green's function (OVGF) calculations at 6-311+G(d, p) basis sets. The
      highest occupied molecular orbital (HOMO) for each compound is the carbonyl
      oxygen lone pair (n(O)), the ionizations of these orbitals are associated with
      the vibrational frequency about 1750 and 1820 cm(-1) reflected on the first band,
      respectively, for acyl nitrites and nitrate. Comparing with the calculated
      energies, it can be concluded that the syn conformers with Cs overall symmetry, a
      planar CC(O)ONO skeleton in nitrites, and a planar CC(O)ON skeleton in nitrates,
      respectively, are the most stable in the gas phase.

PMID- 16434230
TI  - Interaction between force production and cognitive performance in humans.
AB  - OBJECTIVE: A dual task paradigm was used to examine the effects of the generation
      of force on cognitive performance. METHODS: Subjects (n=22) were asked to respond
      to auditory stimuli with their left middle or index finger and concurrently
      maintain a sub-maximal contraction with their right index finger at one of two
      different force levels. The contraction was maintained for approximately 12s and
      the target force level was alternated between 30 and 60% of the maximal force.
      Force production was the primary task of interest; performance of the (secondary)
      choice reaction time task (reaction times and accuracy) was used as an index of
      the amount of interference between the two tasks. RESULTS: All subjects were
      capable of performing the force tasks adequately. Significant interference was
      observed between the level of force production and cognitive performance. At the
      higher force level, subjects performed the cognitive task more slowly and less
      accurately compared to the lower force level. CONCLUSION: Our results show that
      the execution of high-effort motor behaviour interacts with cognitive task
      performance. However, comparison with the data obtained during fatiguing
      contractions in a previous study [Lorist MM, Kernell D, Meijman TF, Zijdewind I.
      Motor fatigue and cognitive task performance in humans. J Physiol 2002;545:313
      319.] showed that the interference was stronger during fatiguing contractions
      than during the present high-effort motor behaviour. SIGNIFICANCE: The results
      suggest that force-related factors can explain part of the fatigue-related
      interference between force production and cognitive performance. This result
      could have consequences for interpreting cognitive deficits observed in patients
      suffering from motor dysfunction.

PMID- 16434231
TI  - Use of electronic pagers to recall patients undergoing outpatient-based
      chemotherapy.
AB  - Long waiting times while receiving chemotherapy in an outpatient setting have
      been identified as contributing to patient dissatisfaction and discomfort by a
      number of authors. Following an observation of this practice in a non-medical
      establishment, and as part of our service improvement program, we introduced the
      use of message pagers to recall patients in our chemotherapy outpatient service.
      We audited the impact of this intervention by means of questionnaires directed at
      patients and nursing staff. Our audit found that this intervention was
      particularly popular with female patients. Perceived benefits included more
      freedom of movement, less boredom, and peace of mind at being contactable. There
      were no reported problems with pager operation. Nursing staff were keen promoters
      of the pagers to patients as they felt that their use gave them more control over
      work intensity and less disruption from patients enquiring about remaining
      "waiting time". We concluded that this intervention may benefit other outpatient
      chemotherapy services.

PMID- 16434232
TI  - Developing advanced clinical skills in the management of breathlessness:
      evaluation of an educational intervention.

PMID- 16434233
TI  - Acute mitral valve dysfunction due to leaflet escape in a Tri-technologies
      bileaflet mechanical valve.
AB  - Acute prosthetic valve dysfunction due to leaflet escape is a mode of structural
      valve failure of mechanical prostheses which is associated with a high mortality.
      In this report, we describe the case of a 32-year-old patient, who underwent
      mitral valve replacement with a Tri-technologies bileaflet valve three years ago,
      and was admitted to the hospital on August 2005, in cardiogenic shock. He
      discontinued oral anticoagulation therapy four months ago. Transthoracic and
      transesophageal echocardiograms showed acute-onset massive mitral regurgitation
      with normal left ventricular function. The patient underwent emergency surgery,
      during which one leaflet was found to be absent and the other leaflet was fixed
      due to prosthetic thrombus.

PMID- 16434234
TI  - Isolated cleft of the anterior mitral valve leaflet.
AB  - Isolated anterior mitral leaflet cleft (not associated with atrio-ventricular
      septal defect) is a rare cause of congenital mitral regurgitation, and the
      treatment consists of direct suturing of the cleft. We present a clinical case
      with this entity.

PMID- 16434236
TI  - Expression of low density lipoprotein receptor-related protein 4 (Lrp4) gene in
      the mouse germ cells.
AB  - The low density lipoprotein receptor-related protein 4 gene (Lrp4) was identified
      by subtractive screening of cDNAs of the migratory primordial germ cells (PGCs)
      of E8.5-9.5 embryo and E3.5 blastocysts. Lrp4 is expressed in PGCs in the hindgut
      and the dorsal mesentery of E9.5 embryos, and in germ cells in the genital ridges
      of male and female E10.5-13.5 embryos. Lrp4 is also expressed in spermatogonia of
      the neonatal and adult testes and in the immature oocytes and follicular cells of
      the adult ovary. The absence of Lrp4 expression in the blastocyst, embryonic stem
      cells and embryonic germ cells suggests the Lrp4 is a molecular marker that
      distinguishes the germ cells from embryo-derived pluripotent stem cells.

PMID- 16434235
TI  - Snake venom metalloproteases--structure and function of catalytic and disintegrin
      domains.
AB  - Snake venoms are relevant sources of toxins that have evolved towards the
      engineering of highly active compounds. In the last years, research efforts have
      produced great advance in their understanding and uses. Metalloproteases with
      disintegrin domains are among the most abundant toxins in many Viperidae snake
      venoms. This review will focus on the structure, function and possible
      applications of the metalloprotease and disintegrin domains.

PMID- 16434237
TI  - Spatio-temporal expression of Pbx3 during mouse organogenesis.
AB  - Pbx3 is a member of the Pbx family of TALE (three amino acid loop extension)
      class homeodomain transcription factors. These transcription factors are
      implicated in developmental and transcriptional gene regulation in numerous cell
      types through their abilities to form hetero-oligomeric DNA-binding complexes.
      Pbx3 was found to be expressed at high levels in the developing central nervous
      system (CNS), including a region of the medulla oblongata which is implicated in
      the control of respiration. Furthermore, as reported, Pbx3-deficient mice develop
      to term but die within a few hours of birth from central respiratory failure. In
      this study, we have characterized Pbx3 expression patterns during organogenesis
      in numerous tissues and organ systems other than the CNS, as a first step toward
      understanding the potentially overlapping functions of Pbx3 with other Pbx family
      members during vertebrate development. We have performed in situ hybridization on
      whole mount and sectioned mouse embryos from gestational day (E) 9 to E16.5.
      During early organogenesis, until E12.5, Pbx3 expression is found mostly in the
      embryonic head, forelimbs, and septum transversum, unlike Pbx1 and Pbx2
      expression which is more widespread. Conversely, later in organogenesis, Pbx3
      expression becomes more widely detectable throughout the developing embryo.
      Epithelial and mesenchymal tissues, as well as the CNS, represent major sites of
      Pbx3 expression. The enteric nervous system also expresses high levels of Pbx3,
      distinctively in the cells of the ganglia of Auerbach's myenteric nerve plexus,
      that also express Dlx2 and Notch1. Cartilage is also a site of Pbx3 expression.
      Interestingly, like Pbx1, Pbx3 is highly expressed in proliferating chondrocytes
      but is lost as chondrocytes become hypertrophic during endochondral ossification.
      Finally, Pbx3 is expressed only in the forelimb buds during early limb
      development, while the hindlimb bud is devoid of Pbx3. This finding leads us to
      add Pbx3 to the sparse list of early forelimb-specific molecular markers.

PMID- 16434238
TI  - Caffeine in the milk prevents respiratory disorders caused by in utero caffeine
      exposure in rats.
AB  - Consequences of postnatal caffeine exposure by the milk on ponto-medullary
      respiratory disturbances observed following an in utero caffeine exposure were
      analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to
      caffeine during gestation but not after the birth display an increase in
      respiratory frequency and an exaggeration of the hypoxic respiratory depression
      compared to not treated preparations. These data suggest that tachypneic and
      apneic episodes encountered in human newborns whose mother consumed caffeine
      during pregnancy are due in large part to central effect of caffeine at the ponto
      medullary level. Both baseline respiratory frequency increase and emphasis of
      hypoxic respiratory depression are not encountered if rat dams consumed caffeine
      during nursing. Our hypothesis is that newborn rats exposed to caffeine during
      gestation but not after the birth would be in withdrawal situation whereas, when
      caffeine is present in drinking fluid of lactating dams, it goes down the milk
      and is able to prevent ponto-medullary respiratory disturbances.

PMID- 16434239
TI  - The role of emerging techniques in the investigation of prolidase deficiency:
      from diagnosis to the development of a possible therapeutical approach.
AB  - The aim of the present article is to review the efforts performed in the past two
      decades by numerous research groups for the development of methods that allow a
      correct diagnosis of prolidase deficiency (PD), a rare autosomal recessive
      disorder and for the rationalization of a possible therapeutic intervention on
      these patients. In particular, the interest of the reader is focused on the
      application of capillary electrophoresis (i) for the detection of biological
      markers that reflect the pathological feature of the disease and (ii) for the
      determination of the efficiency of a carrier system in delivering prolidase
      inside cells in a possible therapy based on enzyme replacement.

PMID- 16434240
TI  - Chiral separation of salbutamol and bupivacaine by capillary electrophoresis
      using dual neutral cyclodextrins as selectors and its application to
      pharmaceutical preparations and rat blood samples assay.
AB  - An attempt for the simultaneous separation of salbutamol (Sal) and bupivacaine
      (Bup) enantiomers was performed by capillary elecytrophoresis with a dual mixture
      of neutral cyclodextrins as chiral selector. The influence on the separation of
      several parameters such as buffer composition, pH, the concentration ratio of 2
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to dimethyl-beta-cyclodextrin (DM
      beta-CD) was investigated. A better separation was obtained for Sal and Bup with
      the CD mixtures compared to the use of HP-beta-CD or DM-beta-CD alone. The best
      simultaneous separation of Sal and Bup enantiomers was achieved with a 20 mM HP
      beta-CD and 20 mM DM-beta-CD at pH 2.5 in a triethanolamine (TEA)/phosphate
      buffer. This method-utilized chlorphenamine (Chl) as an internal standard was
      found to be linear in the range 0.5-100 microg/mL and 0.5-150 microg/mL for Sal
      and Bup enantiomers, respectively. The limits of detection for both enantiomers
      of Sal and Bup were 0.18 and 0.24 microg/mL, respectively. The proposed method
      was applied to monitor Sal and Bup enantiomers concentration change in rat blood
      samples obtained from a male rat after celiac doses administration 0-30 min of
      Sal and Bup racemate. The method could also be used to determine Sal enantiomers
      in a pharmaceutical aerosol.

PMID- 16434242
TI  - Enantioselective assay for the determination of perhexiline enantiomers in human
      plasma by liquid chromatography.
AB  - Effective use of the antianginal agent perhexiline is difficult because saturable
      metabolism by the polymorphic cytochrome P450 2D6 (CYP2D6) isoform produces
      elevated plasma perhexiline concentrations that have been associated with serious
      hepatic and neurological toxicity. Perhexiline is marketed for therapeutic use as
      a racemate and there is evidence for differences in the disposition of its
      enantiomers. The current study describes an enantioselective HPLC-fluorescent
      method utilising pre-column derivatization with (R)-(-)-1-(1-napthyl)ethyl
      isocyanate. Following derivatization, the enantiomers are resolved on a C18
      column with gradient elution using a mobile phase composed of methanol and water.
      The method described is suitable for the quantification of (+)- and (-)
      perhexiline in human plasma following clinical doses and demonstrates sufficient
      sensitivity, accuracy and precision between 0.01 and 2.00 mg/l for each
      enantiomer, with intra-assay coefficients of variation and bias <20% at 0.01 mg/l
      and <10% at 2.00 mg/l, and inter-assay coefficients of variation and biases <15%
      at 0.03 mg/l and <10% at 0.40 and 0.75 mg/l. The application of this method to
      plasma samples collected from a patient treated with perhexiline revealed that
      (+)-perhexiline concentrations were higher than (-)-perhexiline concentrations,
      confirming the stereoselective disposition of perhexiline. The current study
      describes an enantioselective method that utilises pre-column formation of
      fluorescent diastereomers that are resolved on a C18 HPLC column using a gradient
      of methanol and water.

PMID- 16434241
TI  - Determination of St. John's wort flavonoid-metabolites in rat brain through high
      performance liquid chromatography coupled with fluorescence detection.
AB  - Flavonoids with the quercetin structure are widely distributed throughout the
      plant kingdom. Some effects such as their anti-oxidative and radical scavenging
      capacities are broadly discussed in literature. Furthermore, some Hypericum
      flavonoids show activity in depression-relevant animal model assays. So far, only
      one study concerning the pharmacokinetic profile of Hypericum perforatum (St.
      John's wort, SJW) flavonoids has been reported, but no data concerning their
      bioavailability in the CNS is on-hand. Thus, we developed a method for the
      quantification of quercetin, tamarixetin and isorhamnetin, both metabolites of
      quercetin, in very low concentrations in the rat brain in order to investigate
      the ability of flavonoids to cross the blood-brain barrier. The brain samples for
      analysis were taken 4h after feeding an oral dose of an alcoholic SJW extract or
      pure isoquercitrin. We found the presence of quercetin and
      isorhamnetin/tamarixetin after feeding a SJW extract at 7 ng/g brain and 35 ng/g
      brain, respectively. In addition, we examined blood plasma taken from the same
      rats to correlate plasma and brain levels. The plasma levels were 350 ng/mL for
      quercetin and 1006 ng/mL for isorhamnetin/tamarixetin after intake of SJW
      extract.

PMID- 16434243
TI  - Liquid chromatography-tandem mass spectrometry assay of reduced and oxidized
      glutathione and main precursors in mice liver.
AB  - A liquid chromatography/tandem mass spectrometry assay of glutathione (GSH),
      glutathione disulfide (GSSG) and of precursors (gamma-glutamyl-cysteine,
      cysteinyl-glycine, cysteine, cystine, homocysteine and homocystine) was developed
      to study glutathione synthesis in mice liver. After iodoacetic acid
      derivatization, the analytes were analyzed using reversed-phase gradient HPLC and
      detected using multiple reaction monitoring. Linear calibrations were performed
      over the concentrations range of 100-10,000 ng/mL for the thiol-containing
      precursors and extended up to 100,000 ng/mL for GSH and GSSG. The method was
      validated for each compound with inter-day accuracy below 11.9% and with
      precision below 15%. The method showed low limits of quantitation of 100 ng/mL
      for each thiol-containing compound and GSSG and of 200 ng/mL for other
      disulfides.

PMID- 16434244
TI  - Identification of catalytically important amino acid residues of Streptomyces
      lividans acetylxylan esterase A from carbohydrate esterase family 4.
AB  - Multiple sequence alignment of Streptomyces lividans acetylxylan esterase A and
      other carbohydrate esterase family 4 enzymes revealed the following conserved
      amino acid residues: Asp-12, Asp-13, His-62, His-66, Asp-130, and His-155. These
      amino acids were mutated in order to investigate a functional role of these
      residues in catalysis. Replacement of the conserved histidine residues by alanine
      caused significant reduction of enzymatic activity. Maintenance of ionizable
      carboxylic group in side chains of amino acids at positions 12, 13, and 130 seems
      to be necessary for catalytic efficiency. The absence of conserved serine
      excludes a possibility that the enzyme is a serine esterase, in contrast to
      acetylxylan esterases of carbohydrate esterase families 1, 5, and 7. On the
      contrary, total conservation of Asp-12, Asp-13, Asp-130, and His-155 along with
      dramatic decrease in enzyme activity of mutants of either of these residues lead
      us to a suggestion that acetylxylan esterase A from Streptomyces lividans and, by
      inference, other members of carbohydrate esterase family 4 are aspartic
      deacetylases. We propose that one component of the aspartate dyad/triad functions
      as a catalytic nucleophile and the other one(s) as a catalytic acid/base. The
      ester/amide bond cleavage would proceed via a double displacement mechanism
      through covalently linked acetyl-enzyme intermediate of mixed anhydride type.

PMID- 16434245
TI  - Structural analysis of protein inclusion bodies by Fourier transform infrared
      microspectroscopy.
AB  - The expression of recombinant human growth hormone (h-GH) and human interferon
      alpha-2b (IFN-alpha-2b) in E. coli leads to the formation of insoluble protein
      aggregates or inclusion bodies (IBs). The secondary structure of these IBs, their
      corresponding native forms and thermal aggregates were studied by Fourier
      Transform Infrared (FT-IR) spectroscopy and microspectroscopy. It was
      demonstrated that residual native-like structures were maintained within IBs at
      different extents depending on the level of expression, with possible
      implications in biotechnology. Furthermore, comparison between infrared spectra
      of thermal aggregates and IBs suggests new insights on the structure of protein
      aggregates.

PMID- 16434246
TI  - Perinatal research in developing countries--is it possible?
AB  - Maternal mortality remains the health statistic for which there is the greatest
      disparity between developing and developed countries. The risk of stillbirth or
      neonatal death is also high in developing countries. The inequality of research
      funding between rich and poor countries is dramatic, with only 10% of research
      funding directed towards diseases which contribute 90% of the global burden of
      disease. The need for high-quality, relevant perinatal research in developing
      countries is compelling. There are many examples of good perinatal research in
      developing countries. Nevertheless, significant challenges remain and are being
      tackled. We need better information about maternal and perinatal health, and
      about performance of the health services, we need more evaluation of what helps
      and what harms within the existing health services, and we need improved
      strategies for implementation of research findings.

PMID- 16434247
TI  - Protelos: nonvertebral and hip antifracture efficacy in postmenopausal
      osteoporosis.
AB  - Strontium ranelate is a new treatment for postmenopausal osteoporosis,
      simultaneously increasing bone formation and decreasing bone resorption, thus
      rebalancing bone turnover in favor of bone formation. Strontium ranelate was
      demonstrated to significantly reduce the relative risk of vertebral fracture
      whatever the severity of the disease. In the TReatment Of Peripheral OSteoporosis
      (TROPOS) study, the incidence of nonvertebral and hip fractures, following
      treatment with strontium ranelate (Protelos, Servier) at a dosage of 2 g/day
      orally, was assessed over a 3-year period. In this double-blind, placebo
      controlled trial, 5091 women with postmenopausal osteoporosis were assigned to
      either strontium ranelate (n = 2479) or placebo (n = 2453) treatment. Overall,
      the reduction in risk for nonvertebral fractures in patients treated with
      strontium ranelate was 16% (P = 0.04) and for major fractures (hip, wrist, pelvis
      and sacrum, ribs and sternum, clavicle and humerus), it was 19% (P = 0.031),
      compared with those treated with placebo. Women with osteoporosis and aged 74
      years or more who were treated with strontium ranelate (n = 982) had a 36%
      reduction in risk of hip fracture (P = 0.046) over 3 years compared with those
      treated with placebo (n = 995). The difference in bone mineral density between
      groups was 8.2% for femoral neck and 9.8% for total hip at 3 years. The incidence
      of adverse events was comparable between groups. The study demonstrates that
      strontium ranelate treatment offers a safe and effective means of reducing the
      risk of nonvertebral and hip fractures in postmenopausal women with osteoporosis.

PMID- 16434248
TI  - Combined therapy of Sr-89 and zoledronic acid in patients with painful bone
      metastases.
AB  - PURPOSE: We evaluated the pain response and daily discomfort in patients with
      painful bone metastases treated by merging 89Sr-chloride and zoledronic acid. The
      results were compared with those of patients who received 89Sr-chloride or
      zoledronic acid separately. METHODS: 25 patients (12 women; mean age 65+/-13
      years) chronically treated with zoledronic acid underwent bone pain palliation
      with 150 MBq of 89Sr-chloride at least 6 months later that bisphoshonate therapy
      started (group A). 13 patients (6 women; mean age 70+/-12 years) received 89Sr
      chloride alone (group B) and 11 patients (5 women; mean age 69+/-12 years) were
      chronically treated and continued to receive only zoledronic acid therapy (group
      C), both constituted the control groups. Patients kept a daily pain diary
      assessing both their discomfort and the pain of specific sites by using a visual
      analog scale (VAS), rating from 0 (no d iscomfort-no pain) to 10 (worst
      discomfort-pain). These diaries were reviewed weekly for 2 months and three
      different physicians rated the pain response on a scale of -2 (considerable
      deterioration) to +2 (considerable improvement). RESULTS: Baseline
      characteristics were similar in the three groups. The reduction of total
      discomfort and of bone pain in the group A was significantly greater as compared
      to group B (P<0.01) and group C (P<0.01). During the monitored period, a
      significant improvement of clinical conditions was observed in the group A,
      varying the rate from -1 to 1 as compared to both groups B and C in which the
      rate changed from -1 to 0. CONCLUSION: Our findings indicate that combined
      therapy of 89Sr-chloride and zoledronic acid in patients with painful bone
      metastases is more effective in treating pain and improving clinical conditions
      than 89Sr-chloride or zoledronic acid used separately.

PMID- 16434249
TI  - Asymptomatic chest wall Hodgkin disease mimicking fibrosing mediastinitis.

PMID- 16434250
TI  - Device discordancy: lost cords, quick-fix seekers, quality, and ethics.

PMID- 16434251
TI  - Are women different from men in ways that matter? Maybe.

PMID- 16434252
TI  - Inhibition of complement activation in cardiac surgery.

PMID- 16434253
TI  - Effect of closed minimized cardiopulmonary bypass on cerebral tissue oxygenation
      and microembolization.
AB  - OBJECTIVE: Coronary artery bypass grafting with cardiopulmonary bypass carries a
      risk for neurologic complications because of cerebral hypoperfusion and
      microembolization. The basic goals of a novel closed minimized extracorporeal
      circulation are to prevent excessive hemodilution and to avoid blood-air
      interface. The aim of this prospective randomized study was to determine the
      effect of using the minimized extracorporeal circulation system compared with
      open conventional extracorporeal circulation on cerebral tissue oxygenation and
      microembolization. METHODS: Forty patients undergoing coronary artery bypass
      grafting (20 in each group) were continuously monitored for changes in cerebral
      oxygenated hemoglobin and tissue oxygenation index by using near-infrared
      spectroscopy. Total microembolic count and gaseous embolic count in both median
      cerebral arteries were monitored with multifrequency transcranial Doppler
      instrumentation. RESULTS: In the conventional extracorporeal circulation group
      there was a highly significant reduction in both cerebral oxygenated hemoglobin
      and tissue oxygenation index from the start to the end of cardiopulmonary bypass
      (P < .01). The rate of decrease in cerebral oxygenated hemoglobin after aortic
      cannulation was faster in the conventional extracorporeal circulation group (F
      test = 9.03, P < .001). No significant changes with respect to cerebral
      oxygenated hemoglobin or tissue oxygenation index occurred in the minimized
      extracorporeal circulation group, except at the beginning of rewarming (P < .01).
      Total embolic count, as well as gaseous embolic count, in the left and right
      median cerebral arteries was significantly lower in the minimized extracorporeal
      circulation group (all P < .05). Postoperative bleeding was greater (P < .05) and
      the transfusion rate was higher (P < .05) in the conventional extracorporeal
      circulation group. CONCLUSIONS: Use of closed minimized cardiopulmonary bypass
      compared with conventional open cardiopulmonary bypass preserves cerebral tissue
      oxygenation and reduces cerebral microembolization.

PMID- 16434254
TI  - Stress doses of hydrocortisone reduce chronic stress symptoms and improve health
      related quality of life in high-risk patients after cardiac surgery: a randomized
      study.
AB  - OBJECTIVES: Improvement in health-related quality of life is a major object of
      cardiac surgery. However, high stress exposure during the perioperative period of
      cardiac surgery can result in the formation of traumatic memories and symptoms of
      chronic stress or even posttraumatic stress disorder, which can have negative
      effects on health-related quality-of-life outcome. In this controlled study we
      examined whether exogenously administered stress doses of hydrocortisone during
      cardiac surgery reduce perioperative stress exposure and the long-term incidence
      of chronic stress symptoms and improve health-related quality of life after
      cardiac surgery. METHODS: Thirty-six high-risk patients undergoing cardiac
      surgery were prospectively randomized to receive either stress doses of
      hydrocortisone or placebo. Of 28 available patients at 6 months after cardiac
      surgery, 14 had received hydrocortisone, and 14 had received placebo. Traumatic
      memories, chronic stress symptoms (posttraumatic stress disorder scores), and
      health-related quality of life were measured by using validated questionnaires.
      RESULTS: Compared with patients from the placebo group, patients from the
      hydrocortisone group had a significantly shorter duration of intensive care unit
      treatment, required lower doses of the stress hormone norepinephrine during
      cardiac surgery, and had significantly fewer stress symptoms and a better health
      related quality of life regarding physical function, chronic pain, general
      health, vitality, and mental health during follow-up. The groups did not differ
      with regard to the number or type of intensive care unit-related traumatic
      memories. CONCLUSIONS: The use of stress doses of hydrocortisone in high-risk
      cardiac surgical patients reduces perioperative stress exposure, decreases
      chronic stress symptoms, and improves health-related quality of life at 6 months
      after cardiac surgery.

PMID- 16434255
TI  - Intraluminal aortic manipulation by means of intra-aortic filter, cannulation,
      and external clamp maneuvers evaluated versus dislodged embolic material.
AB  - OBJECTIVES: Aortic atherosclerosis is an important risk factor for
      cerebrovascular accidents in cardiac surgery. An intra-aortic filter might reduce
      this risk. We aimed to analyze the risks for emboli associated with intraluminal
      aortic manipulation and intra-aortic filter handling in relation to cannulation
      and external clamp maneuvers. METHODS: A model was designed with a cadaver aorta
      and retrograde perfusion (n = 16). A crossclamp was positioned on the ascending
      aorta and repeatedly opened under pressure to collect aliquots with dislodged
      particles. Cannulation was performed after 10 clamp maneuvers, followed by
      positioning and removing the intra-aortic filter, with each step followed by a
      washout sequence to collect perfusate. The removed filter was also analyzed.
      Evaluation was by means of digital image analysis, with differentiation of
      particles into different spectra. RESULTS: Intra-aortic filter manipulation
      produced a significant washout of embolic particles; in particular, this was seen
      for the macroscopic cellular spectrum (P = .006 and P = .002 for filter insertion
      and removal, respectively). Particles were also found to be collected by the
      filter (P = .004). In addition, cannulation and aortic crossclamp manipulation
      generated a notable number of particles (P = .001 and P = .013, respectively).
      CONCLUSIONS: The intra-aortic filter collects material during aortic
      manipulation. However, intraluminal aortic manipulation from filter handling can
      also dislodge particles, possibly related to shedding of intimal debris. This is
      in addition to substantial amounts of particles that are generated by aortic
      cannulation and aortic crossclamping.

PMID- 16434256
TI  - Activation of the coagulation system during coronary artery bypass grafting:
      comparison between on-pump and off-pump techniques.
AB  - OBJECTIVE: The activation of the coagulation and fibrinolytic systems and
      platelet function in patients undergoing coronary artery bypass surgery on-pump
      or off-pump techniques was compared. METHODS: Thirty-two patients were randomly
      assigned to on-pump or off-pump coronary artery bypass grafting. Heparin was
      given at the same dose. Activation of the coagulation and fibrinolytic systems
      was evaluated by measurement of several markers. Platelet function was evaluated
      by in vitro bleeding time test. Blood samples were collected at 7 different
      times, up to postoperative day 6. RESULTS: Overall tissue factor production was
      similar in the two groups. Thrombin formation was more elevated in the on-pump
      group (P < .001), particularly during the operation; prothrombin fragment 1.2
      discharge values were higher than the preoperative ones (P = .002). Levels of
      tissue-plasminogen activator showed no difference between the groups (P = .1). D
      dimers release was higher in the on-pump group (P = .0002). In vitro bleeding
      time was longer in the on-pump group (P < .0001), particularly in the first 24
      hours; it was not prolonged in the off-pump group. In both groups, regardless of
      aspirin treatment, discharge in vitro bleeding times were lower than the
      preoperative ones (P < .01). CONCLUSION: Although the extrinsic coagulation
      pathway is similarly activated, thrombin formation is more pronounced in patients
      having on-pump bypass grafting. Patients subjected to off-pump bypass grafting
      have normally functioning platelets and a weak activation of the fibrinolytic
      system. At discharge, both groups have preserved platelet function and increased
      thrombin formation. Further studies with angiographic evaluation are needed to
      establish a correlation between coagulation parameters, platelet function, and
      graft patency.

PMID- 16434257
TI  - Depletion of DNA methyltransferase 1 and/or DNA methyltransferase 3b mediates
      growth arrest and apoptosis in lung and esophageal cancer and malignant pleural
      mesothelioma cells.
AB  - OBJECTIVE: DNA methyltransferase (DNMT)1, DNMT3b, or both, facilitate malignant
      transformation through chromatin remodeling mechanisms. The present study was
      undertaken to examine the effects of antisense-mediated inhibition of DNMT
      expression in cultured thoracic malignancies. METHODS: CALU-6 and A549 lung
      cancer, SKGT5 and BIC esophageal adenocarcinoma, and H2373 and H2052 malignant
      pleural mesothelioma (MPM) cells, as well as normal human bronchial epithelial
      (NHBE) cells, were transfected with phosphorothioate-modified antisense oligos
      targeting DNMT1, DNMT3b, or both, or mismatch oligos. Quantitative reverse
      transcription-polymerase chain reaction, Western blotting, trypan blue exclusion,
      and ApoBrdU techniques were used to evaluate DNMT expression, proliferation, and
      apoptosis after antisense oligo transfections. Gene expression profiles were
      assessed by using long-oligo array techniques. RESULTS: Antisense oligos mediated
      specific and dose-dependent depletion of DNMT1 and DNMT3b, resulting in
      pronounced inhibition of proliferation of all thoracic cancer lines, but not NHBE
      cells. Depletion of DNMT1 or DNMT3b coincided with dramatic, caspase-dependent,
      p53-independent apoptosis in 4 of the 6 thoracic cancer lines. The
      antiproliferative effects of the antisense oligos were not attributable to
      induction of RASSF1A, p16, or p21 tumor suppressor genes, and did not coincide
      with demethylation of genes encoding cancer-testis antigens. DNA
      methyltransferase knockdown mediated induction of numerous genes regulating
      response to genotoxic stress. Gene expression profiles after DNMT1, DNMT3b, or
      combined DNMT1/3b depletion were remarkably similar, yet distinctly different
      from expression profiles mediated by 5 aza 2' deoxycytidine. CONCLUSIONS:
      Antisense oligos targeting DNMT1 and DNMT3b induce genomic stress, and mediate
      potent growth inhibition in lung and esophageal cancer and MPM cells. These
      findings support further evaluation of DNMT knockdown strategies for cancer
      therapy.

PMID- 16434258
TI  - Outcomes of pulmonary endarterectomy for treatment of extreme thromboembolic
      pulmonary hypertension.
AB  - OBJECTIVE: Pulmonary endarterectomy is the operation of choice for thromboembolic
      pulmonary hypertension. As the largest referral center for thromboembolic
      pulmonary hypertension in the world, we are frequently asked whether patients
      with extreme pulmonary hypertension (pulmonary artery systolic pressure >100 mm
      Hg) can safely undergo this operation with therapeutic benefit. METHODS: To
      determine whether patients with pulmonary artery systolic pressures of greater
      than 100 mm Hg have favorable outcomes after pulmonary endarterectomy, we
      reviewed the outcomes of 743 patients who underwent this operation between 1999
      and 2004. We compared hemodynamic and outcome parameters of 65 patients (group 1:
      26 male and 39 female patients; mean age, 49.5 years) who had preoperative
      pulmonary artery systolic pressures of greater than 100 mm Hg with 678 patients
      (group 2: 314 male and 364 female patients; mean age, 50.3 years) with
      preoperative pulmonary artery systolic pressures of less than 100 mm Hg. RESULTS:
      Group 1 patients had a greater overall diminution in pulmonary vascular
      resistance (mean decrease: 926.7 +/- 511.1 vs 546.4 +/- 365.1 dynes x sec x cm(
      5), P < .01) and reduction in pulmonary artery systolic pressure (mean decrease:
      50.5 +/- 18.7 vs 27.2 +/- 18.6 mm Hg, P < .05), with similar improvement in
      cardiac output (mean increase: 1.53 +/- 1.47 vs 1.55 +/- 1.58 L/min) compared
      with values seen in group 2 patients. Although length of hospital stay was
      similar for the 2 groups, overall perioperative survival was slightly lower in
      group 1 patients (89.2% [58/65] for group 1 vs 96.5% [654/678] for group 2).
      Patients with extreme pulmonary hypertension manifest a higher rate of
      postoperative reperfusion edema, leading to longer days of intubation compared
      with group 2 patients. CONCLUSIONS: Pulmonary endarterectomy can be performed
      safely in patients with severe thromboembolic pulmonary hypertension. The
      magnitude of preoperative pulmonary artery systolic pressure or pulmonary
      vascular resistance is not a contraindication for surgical intervention. Indeed,
      patients with extreme pulmonary hypertension might benefit the most from this
      operation.

PMID- 16434260
TI  - Videothoracoscopic talc poudrage in primary spontaneous pneumothorax: a single
      institution experience in 861 cases.
AB  - OBJECTIVE: We sought to evaluate the outcome of 861 patients treated with
      videothoracoscopic talc poudrage for primary spontaneous pneumothorax. METHODS:
      From September 1995 through January 2004, a total of 861 patients (578 male, 283
      female, mean age 28.6 years) underwent videothoracoscopy for recurrent and
      complicated primary spontaneous pneumothorax. Patients were treated with
      videothoracoscopic talc poudrage only (group A: Vanderschueren's stage I, 196
      patients; stage II, 112 patients) or videothoracoscopic talc poudrage plus
      stapling of the blebs/bullae (group B: stage III, 391 patients; stage IV 162
      patients). Follow-up included clinical interview and chest radiography (805
      patients). In 26 patients (follow-up longer than 5 years), respiratory function
      was investigated to determine residual volume and diffusing lung capacity.
      RESULTS: No operative deaths occurred. No patient had adult respiratory distress
      syndrome. Postoperative complications occurred in 29 patients (3.36%). The
      conversion rate to an open procedure was 0.46% (4/861). After a mean follow-up of
      52.5 months, 14 patients had recurrences (1.73%). The recurrence rate was 2.41%
      (7/290) in group A and 1.359% (7/515) in group B (chi2 value: 1.207389; P:.27;
      odds ratio: 0.56; 95% confidence interval: 0.20-1.62). Results of respiratory
      function tests were within normal ranges (80% or more of predictive value) in all
      26 patients. CONCLUSIONS: Videothoracoscopic talc poudrage achieves a high
      success rate in the treatment of primary spontaneous pneumothorax with a very low
      morbidity rate. Recurrences show a statistically significant relationship
      (P:.037) with smoking habits.

PMID- 16434259
TI  - Multimodality treatment of unresectable stage III non-small cell lung cancer:
      interim analysis of a phase II trial with preoperative gemcitabine and concurrent
      radiotherapy.
AB  - OBJECTIVE: We report the preliminary results of a phase II trial undertaken to
      determine the feasibility and efficacy of gemcitabine and concurrent radiotherapy
      in patients with inoperable stage III non-small cell lung cancer. METHODS:
      Between February 2001 and June 2003, a total of 46 patients (37 male and 9
      female, median age 64 years) with clinical stage III non-small cell lung cancer
      (41 cIIIA and 5 cIIIB) were enrolled in a combined chemoradiation protocol with
      gemcitabine as the chemotherapeutic agent. Gemcitabine (350 mg/m2) was
      administered weekly for 5 consecutive weeks as a 30-minute intravenous infusion
      before radiotherapy (total dose 50.4 Gy, 1.8 Gy/d). Toxicity was routinely
      assessed. Those patients with disease judged to be resectable at restaging
      underwent surgery. RESULTS: Toxicity was moderate, with the exception of 1 grade
      3 thrombocytopenia. All but 5 patients were available for restaging. No complete
      responses were observed. Thirty-four patients (82.9%) had partial responses, 5
      (12.2%) had stable disease, and 2 (4.9%) had progressive disease. Twenty-nine of
      46 patients (63%, 27 cIIIA and 2 cIIIB) underwent surgery. Radical resection was
      possible in all cases. Surgery included 17 lobectomies, 4 bilobectomies, and 8
      pneumonectomies. There were no deaths. Morbidity was 13.8% (4/29). Pathologic
      downstaging to stage 0 or I was observed in 18 patients (39%, 18/46). After a
      median follow-up of 13 months (range 2-28 months), 24 of the patients who had
      undergone operation (86.2%) were alive, with a median disease-free survival of 16
      months. Overall 2-year survival was 66.1%, with a significant difference between
      resected and unresected disease (82% vs 36%, P = .0002). CONCLUSION: The results
      of this induction trial confirm the feasibility and the efficacy of gemcitabine
      with concurrent radiotherapy.

PMID- 16434261
TI  - Reoperation is not an independent predictor of mortality during aortic valve
      surgery.
AB  - OBJECTIVE: Reoperations on aortic valves are associated with increased mortality,
      which may affect valve prosthesis selection at the time of initial aortic valve
      replacement. We analyzed our experience to determine whether reoperation itself
      independently predicts mortality during aortic valve surgery. METHODS:
      Demographic, intraoperative, and outcome data were collected prospectively on
      patients undergoing primary or redo aortic valve replacement or Bentall
      procedures after previous aortic valve replacement with or without concomitant
      coronary bypass grafting at a single institution from 1990 through 2002. Logistic
      regression analyses validated by means of bootstrap methodology identified the
      predictors of hospital mortality and the independent effect of reoperation.
      RESULTS: Of 2673 patients undergoing aortic valve surgery, 2375 were primary
      operations, 216 were reoperations, and 82 were Bentall-after-aortic valve
      replacement procedures. Of 298 reoperations, 32 were third and 5 were fourth
      procedures. Mortality was 2.3% for primary operations, 4.6% for redo aortic valve
      replacement, and 2.4% for Bentall-after-aortic valve replacement procedures. Most
      patients underwent elective procedures, with mortalities of 1.6%, 1.7%, and 2.5%,
      respectively. Hospital mortality was independently predicted by peripheral
      vascular disease (odds ratio, 3.6), active endocarditis (odds ratio, 2.9),
      worsening New York Heart Association class (odds ratio, 2.3), and need for
      annular enlargement (odds ratio, 2.1). Reoperation itself did not predict
      hospital mortality. CONCLUSIONS: The risk of mortality during aortic valve
      surgery is due mostly to active endocarditis, New York Heart Association class,
      and comorbidity. We failed to find a significant effect of reoperation on
      perioperative mortality. Mechanical valves, with their attendant anticoagulation
      related morbidity, should not be implanted solely because of anticipated high
      mortality associated with bioprosthetic rereplacement.

PMID- 16434262
TI  - Extensive deployment of the stented elephant trunk is associated with an
      increased risk of spinal cord injury.
AB  - OBJECTIVE: Thoracic aortic aneurysm repair with the stented elephant trunk
      technique seems to be associated with an increased risk of spinal cord injury. We
      investigated whether severe atherosclerosis of the distal landing zone or
      extensive deployment of the stented elephant trunk is associated with increased
      risk of spinal cord injury. METHODS: Twenty-five patients underwent thoracic
      aortic aneurysm repair with the stented elephant trunk technique. The study
      population included 19 men and had a mean age of 73 +/- 7 years. All patients
      underwent a median sternotomy with cardiopulmonary bypass and selective cerebral
      perfusion. The elephant trunk was fixed with a Z-stent distal to the aneurysm
      during hypothermic circulatory arrest. Thirteen patients underwent concomitant
      total aortic arch replacement. RESULTS: Six (24%) patients had spinal cord
      injury. The presence of severe atherosclerosis at the distal landing zone
      demonstrated a tendency to increase the incidence of spinal cord injury (36% vs
      9%, P = .1218). More distal deployment of the stented elephant trunk was
      significantly associated with increased risk of spinal cord injury (T8.0 +/- 0.6
      vs T6.5 +/- 1.1, P = .0043). Univariate logistic regression analysis identified a
      history of abdominal aortic aneurysm repair (P = .0296) and the vertebral level
      of the distal landing zone (P = .0249) as significant independent risk factors
      for spinal cord injury, and only the latter was significant in multivariate
      analysis (P = .0396). The combination of a distal landing zone of T7 or greater
      and a history of abdominal aortic aneurysm repair was the strongest predictor for
      spinal cord injury (71% vs 6%, P = .0047). CONCLUSIONS: Spinal cord injury after
      stented elephant trunk deployment might be related to occlusion of the excessive
      intercostal arteries or thromboembolism. Patients with a history of abdominal
      aortic aneurysm repair who require extensive deployment of the stented elephant
      trunk seem to be at a higher risk for spinal cord injury.

PMID- 16434263
TI  - Assessment of independent predictors for long-term mortality between women and
      men after coronary artery bypass grafting: are women different from men?
AB  - OBJECTIVE: The long-term mortality of coronary artery bypass grafting in women in
      not certain. The purpose of this study was to determine and compare risk factors
      for long-term mortality in women and men undergoing coronary artery bypass
      grafting. METHODS: Between 1992 and 2002, 3760 consecutive patients (2598 men and
      1162 women) underwent isolated coronary artery bypass grafting. Long-term
      survival data were obtained from the National Death Index (mean follow-up, 5.1 +/
      3.2 years). Multivariable Cox regression analysis was performed, including 64
      preoperative, intraoperative, and postoperative factors separately in women and
      men. RESULTS: There were no differences in in-hospital mortality (2.7% in men vs
      2.9% in women, P = .639) and 5-year survival (82.0% +/- 0.8% in men vs 81.1% +/-
      1.3% in women, P = .293). After adjustment for all independent predictors of long
      term mortality, female sex was an independent predictor of improved 5-year
      survival (hazard ratio, 0.82; 95% confidence interval, 0.71-0.96; P = .014).
      Twenty-one independent predictors for long-term mortality were determined in men,
      whereas only 12 were determined in women. There were 9 common risk factors (age,
      ejection fraction, diabetes mellitus, > or =2 arterial grafts, postoperative
      myocardial infarction, deep sternal wound infection, sepsis and/or endocarditis,
      gastrointestinal complications, and respiratory failure); however, their weights
      were different between women and men. Malignant ventricular arrhythmias,
      calcified aorta, and preoperative renal failure were independent predictors only
      in women. Emergency operation, previous cardiac operation, peripheral vascular
      disease, left ventricular hypertrophy, current and past congestive heart failure,
      chronic obstructive pulmonary disease, body mass index of greater than 29,
      preoperative dialysis, thrombolysis within 7 days before coronary artery bypass
      grafting, intraoperative stroke, and postoperative renal failure were independent
      predictors only in men. CONCLUSIONS: Despite equality between sexes in early
      outcome and superiority of female sex in long-term survival, there were 3
      independent predictors for long-term mortality after coronary artery bypass
      grafting unique for women compared with 12 for men. Clinical decision making and
      follow-up should not be influenced by stereotypes but by specific findings.

PMID- 16434264
TI  - Inhibition of complement activation by pexelizumab reduces death in patients
      undergoing combined aortic valve replacement and coronary artery bypass surgery.
AB  - OBJECTIVE: We sought to evaluate the effects of pexelizumab, a C5 complement
      inhibitor, on death and myocardial infarction in patients undergoing combined
      aortic valve replacement and coronary artery bypass grafting surgery. METHODS:
      The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary
      Artery Bypass Graft surgery trial, a phase III prospective, randomized, double
      blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The
      primary end point was the composite of death, myocardial infarction, or both at
      postoperative day 30 in patients undergoing coronary artery bypass grafting
      without valve surgery. Postoperative myocardial infarction was defined as a
      creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial
      infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or
      new Q-wave evidence of myocardial infarction by postoperative day 30. Because
      patients undergoing coronary artery bypass grafting with a valve procedure were
      not included in the primary population, separate analysis of death and myocardial
      infarction was conducted in 218 patients undergoing combined aortic valve
      replacement and coronary artery bypass grafting surgery. RESULTS: Of the 353
      patients randomized to any valve procedure, 106 (61%) underwent combined aortic
      valve replacement and coronary artery bypass grafting in the pexelizumab
      treatment group compared with 112 (63%) patients in the placebo group. Coronary
      artery bypass grafting was performed with 1 or more internal thoracic artery
      grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179
      (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11
      (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the
      active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P
      =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial
      infarction 30 days after surgical intervention was identical in the 2 groups, but
      the study was not designed to detect differences in this cohort of patients.
      CONCLUSIONS: Inhibition of complement activation by pexelizumab resulted in a
      decreased mortality at 180 days among 218 patients who underwent combined aortic
      valve replacement and coronary artery bypass grafting surgery. Additional studies
      are warranted to confirm this decrease in mortality with pexelizumab in combined
      aortic valve replacement and coronary artery bypass grafting procedures.

PMID- 16434265
TI  - Surgical ventricular reverse remodeling in severe ischemic dilated
      cardiomyopathy: the relevance of the left ventricular equator as a prognostic
      factor.
AB  - OBJECTIVES: Surgical ventricular reverse remodeling has been shown to possibly
      improve hemodynamics and symptoms, but effects on long-term mortality are not
      established. No consistent data are available on which patients will benefit most
      from this procedure. This study was designed to analyze the predictors of long
      term survival after surgical ventricular reverse remodeling in patients with
      ischemic cardiomyopathy. METHODS: Eighty-five patients who underwent surgical
      ventricular reverse remodeling between May 1991 and October 2003 were
      retrospectively analyzed. Left ventricular wall motion and left ventricular
      equatorial diameter were assessed by means of angioventriculography. Left
      ventricular ejection fraction and volumes were measured by means of
      echocardiography. Cox regression analysis was used in several combinations to
      create a final model for identifying predictors of death. RESULTS: Actuarial
      survival after 1, 3, 5, and 10 years was 89%, 79%, 75%, and 75%, respectively.
      New York Heart Association class improved from 2.9 +/- 1.0 to 1.3 +/- 0.5 (P <
      .0001), left ventricular ejection fraction increased from 27.6% +/- 6.3% to 43.0%
      +/- 10.1% (P < .0001), and left ventricular end-systolic volume index decreased
      from 89.6 +/- 27.6 mL/m2 to 56.5 +/- 34.5 mL/m2 (P < .0001). Multivariate
      analysis identified left ventricular equatorial diameter of 70 mm or greater
      (hazard ratio, 5.28; 95% confidence interval, 1.79-11.71; P = .020) and segmental
      akinesia (hazard ratio, 4.46; 95% confidence interval, 1.23-17.12; P = .024) as
      the only independent predictors of death. CONCLUSIONS: In this analysis of a
      single cohort of patients, surgical ventricular reverse remodeling improves the
      symptoms of ischemic cardiomyopathy, as well as left ventricular function, shape,
      and volume, with encouraging long-term outcomes, particularly in patients with
      dyskinesia. A left ventricular equatorial diameter of 70 mm or greater appears to
      be an important independent prognostic factor, which suggests the relevance of
      the left ventricular equatorial region for effective surgical reverse remodeling.

PMID- 16434266
TI  - Similar long-term results of mitral valve repair for anterior compared with
      posterior leaflet prolapse.
AB  - OBJECTIVE: The results of mitral valve repair for anterior leaflet prolapse have
      been less gratifying than those reported for posterior leaflet prolapse. We
      compared the long-term durability of 2 different surgical techniques: the edge-to
      edge repair, which is used for the treatment of anterior leaflet prolapse, and
      quadrangular resection, which has been adopted for correction of posterior
      leaflet prolapse. METHODS: From 1991 through April 2004, 133 patients with
      anterior leaflet prolapse and 605 with posterior leaflet prolapse caused by
      degenerative mitral disease underwent valve repair. The edge-to-edge repair was
      used for correction of anterior leaflet prolapse, and quadrangular resection of
      the posterior leaflet, with or without sliding plasty, was used for correction of
      posterior leaflet prolapse. All patients received a concomitant annuloplasty
      procedure. RESULTS: No hospital deaths occurred in the anterior leaflet prolapse
      group, whereas 2 (0.3%) patients died in the posterior leaflet prolapse group (P
      = .7). Follow-up was 100% and 97.2% complete in the anterior and posterior
      leaflet prolapse groups, respectively. At 10 years, overall survival was 91% +/-
      4.06% for anterior leaflet prolapse and 93.5% +/- 1.81% for posterior leaflet
      prolapse (P = .18), and freedom from cardiac death was 95.8% +/- 2.83% for
      anterior leaflet prolapse and 97.4% +/- 0.95% posterior leaflet prolapse (P =
      .27). Freedom from reoperation was 96% +/- 2.3% in the anterior leaflet prolapse
      group and 96.5% +/- 1.18% in the posterior leaflet prolapse group (P = .37). At
      follow-up (mean, 4.5 +/- 3.12 years; range, 1 month-13.2 years), New York Heart
      Association functional class I or II was documented in 93.2% of patients in the
      anterior leaflet prolapse group and 92.8% in the posterior leaflet prolapse group
      (P = .98). CONCLUSIONS: The long-term results of the edge-to-edge repair in the
      setting of anterior leaflet prolapse are similar to those obtained with
      quadrangular resection for the treatment of posterior leaflet prolapse.

PMID- 16434267
TI  - Regional cerebral saturation monitoring with near-infrared spectroscopy during
      selective antegrade cerebral perfusion: diagnostic performance and relationship
      to postoperative stroke.
AB  - OBJECTIVE: To investigate whether regional cerebral tissue oxygen saturation
      monitoring during hypothermic selective antegrade cerebral perfusion in surgery
      involving the aortic arch can predict neurologic sequelae and to evaluate the
      diagnostic performance of near-infrared spectroscopy monitoring in this setting.
      METHODS: Data from 46 consecutive patients were analyzed. Selective antegrade
      cerebral perfusion was established by perfusion of the right subclavian artery
      (with or without left carotid artery perfusion) or by separate concomitant
      perfusion of the innominate and the left carotid arteries. The bilateral regional
      cerebral tissue oxygen saturation index was monitored by using near-infrared
      spectroscopy equipment (INVOS 4100). Stroke was the primary clinical end point,
      along with the indices of diagnostic performance. RESULTS: Six patients died in
      the hospital, and 6 patients (13%) experienced a perioperative stroke. In
      patients with stroke, regional cerebral tissue oxygen saturation values were
      significantly lower during selective antegrade cerebral perfusion, and regional
      cerebral tissue oxygen saturation tended to be lower in the affected hemisphere.
      In receiver operating characteristic curve analysis, the area under the curve for
      relative regional cerebral tissue oxygen saturation values ranged from 0.72 to
      0.87. During selective antegrade cerebral perfusion, regional cerebral tissue
      oxygen saturation between 76% and 86% of baseline had a sensitivity up to 83% and
      a specificity up to 94% in identifying individuals with stroke. The associated
      odds ratio for stroke was 5.6 (95% confidence interval, 0.5-144) to 21 (95%
      confidence interval, 1.8-566). CONCLUSIONS: Monitoring of regional cerebral
      tissue oxygen saturation by using near-infrared spectroscopy during selective
      antegrade cerebral perfusion allows detection of clinically important cerebral
      desaturation. It can help predict perioperative neurologic sequelae. Its
      performance as a diagnostic instrument is satisfying and supports its use as a
      noninvasive trend monitor of cerebral saturation.

PMID- 16434268
TI  - Endovascular repair of the thoracic aorta necessitating anchoring of the stent
      graft across the arch vessels.
AB  - OBJECTIVE: The purpose of the study was to determine technical and clinical
      results in endovascular repair of thoracic aortic diseases necessitating stent
      graft anchoring across the arch vessels. METHODS: The causes for endovascular
      treatment in 58 patients (aged 20 to 84 years) were aneurysms (n = 32), acute
      type A (n = 2) and type B dissections (n = 17), posttraumatic transections (n =
      4), iatrogenic dissection (n = 1), and penetrating ulcers with an intramural
      hematoma (n = 2). Surgical revascularization of arch vessels was performed in 26
      patients before stent-graft implantation. Intentional overstenting of the left
      subclavian artery resulted in complete occlusion in 8 and was partial in 24
      patients. RESULTS: The 30-day mortality rate was 3.4%. Overall, 19 major
      postprocedural complications occurred in 14 (24%) patients. Among patients with
      left subclavian artery occlusion, 2 patients had major (1 paraplegia, 1 critical
      arm ischemia), and 3 minor (2 temporary vertebrobasilary symptoms, 1 transient
      arm claudication) complications. Fourteen (25%) patients had an early endoleak,
      of whom 5 were treated successfully with a secondary endovascular procedure, 2
      necessitated open surgical conversion, and 7 were treated conservatively, with
      spontaneous sealing of the endoleak in 3. In 53 (91%) in whom computed
      tomographic follow-up was longer than 3 months (mean, 30.1 months, range, 3 to
      85), the aortic diameter along the stented segment decreased in 24, was stable in
      19, and increased in 10 patients. CONCLUSION: Fixation of the stent graft in the
      aortic arch can expand the applicability of endovascular repair. Intentional
      overstenting should be performed with caution to avoid ischemic problems after
      complete occlusion of left subclavian artery.

PMID- 16434269
TI  - Endoscopic versus conventional radial artery harvest for coronary artery bypass
      grafting: functional and histologic assessment of the conduit.
AB  - BACKGROUND: The radial artery's propensity for vasospasm and vulnerability to
      surgical trauma are well known. A less invasive endoscopic method to harvest the
      radial artery was recently introduced, but its effect on radial artery integrity
      is unknown. METHODS: To compare the effects of harvest method on radial artery
      function, we prospectively randomized 54 patients undergoing coronary artery
      bypass grafting with the radial artery into 3 groups on the basis of harvest
      techniques: endoscopic, conventional with cautery, and conventional with harmonic
      scalpel. We assessed endothelium-dependent and endothelium-independent relaxation
      of radial artery segments to sequential doses of acetylcholine and nitroglycerin,
      respectively, using standard organ-chamber methodology. Vasospasm was assessed as
      the vasoconstrictor response to the thromboxane analog U46619. We assessed
      endothelial integrity using light and electron microscopy and by rating
      intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and P
      selectin expression by means of immunohistochemistry on a semiquantitative 0- to
      3-point scale. Harvest procedures were performed by a single surgeon, and data
      analyses were blinded to the harvesting method. RESULTS: Maximal relaxation
      contraction responses to acetylcholine, nitroglycerin, and U46619 and effective
      drug concentration yielding 50% response were similar in the 3 groups. Adhesion
      molecule expression and histologic changes, as assessed by means of light and
      electron microscopy, were similar in the 3 groups. CONCLUSIONS: Endoscopic
      harvest does not alter radial artery vasoreactivity or endothelial integrity
      compared with conventional harvest techniques. Because the endoscopic technique
      is less invasive, it might prove to be the technique of choice to harvest the
      radial artery.

PMID- 16434270
TI  - Near-infrared spectroscopy to monitor cerebral oxygen saturation in single
      ventricle physiology.
AB  - OBJECTIVES: Near-infrared spectroscopy monitors cerebral oxygen saturation. This
      parameter parallels jugular venous oxygen saturation and reflects the balance
      between cerebral oxygen supply and demand. Experience with near-infrared
      spectroscopy in univentricular physiology is limited. This study explores the
      relationship between cerebral oxygen saturation, jugular venous oxygen
      saturation, and other variables of cerebral perfusion in a model of
      univentricular physiology. METHODS: Univentricular physiology was created in
      newborn piglets by means of an aortopulmonary shunt, echocardiography-guided
      atrial septostomy, tricuspid valve avulsion, and pulmonary artery occlusion.
      Intra-aortic balloon inflation was used to increase afterload. Cerebral oxygen
      saturation monitoring (INVOS 5100; Somanetics Corp, Troy, Mich), physiologic
      recordings, and stable-isotope microsphere determination of cerebral blood flow
      were performed at baseline and after conversion to univentricular physiology (30
      minutes, 120 minutes, and during afterload augmentation). RESULTS: Univentricular
      physiology resulted in lower cerebral oxygen saturation, arterial oxygen content,
      jugular venous oxygen saturation, and cerebral oxygen delivery. Afterload
      augmentation increased cerebral oxygen saturation, arterial oxygen content, and
      jugular venous oxygen saturation, whereas cerebral oxygen delivery was unaffected
      because of lower cerebral blood flow. Cerebral oxygen saturation predicted
      jugular venous oxygen saturation, arterial oxygen saturation, and arterial oxygen
      content. No association was found with cerebral oxygen delivery, which decreased
      in parallel with cerebral oxygen saturation when the single-ventricle physiology
      model was established but failed to increase during afterload augmentation.
      CONCLUSIONS: This study shows that in univentricular physiology cerebral oxygen
      saturation correlates well with jugular venous oxygen saturation, arterial oxygen
      saturation, and arterial oxygen content. However, our findings suggest that in
      singe-ventricle physiology changes in cerebral oxygen saturation need to be
      interpreted in the context of changes in arterial oxygenation.

PMID- 16434271
TI  - Epicardial beating heart cryoablation using a novel argon-based cryoclamp and
      linear probe.
AB  - OBJECTIVE: Epicardial, beating heart cryoablation for the treatment of atrial
      fibrillation may be limited by heat from intracardiac blood flow. We therefore
      evaluated the ability to create cryolesions using an argon-based cryoclamp
      device, which temporarily occludes blood flow and facilitates transmurality.
      METHODS: Six mongrel dogs underwent sternotomy. A clamp employing a 10-cm argon
      based linear cryoablation device was used epicardially to isolate the pulmonary
      veins and left atrial appendage. After clamping of lesions, the probe was removed
      from the cryoclamp device, and the remaining linear lesions, analogous to the Cox
      maze III, were performed. Pulmonary vein stenosis was evaluated with the use of
      magnetic resonance imaging. Left atrial function and pulmonary venous flow
      velocities were assessed with transesophageal echocardiography. Transmurality was
      confirmed both electrically and histologically. Animals were then put to death at
      30 days. RESULTS: All acute and chronic cryoclamp lesions produced conduction
      block. There was no change in right (RPV) or left pulmonary vein (LPV) diameter
      on the basis of magnetic resonance imaging at baseline and at planned death (RPV
      1, 19.6 +/- 2.9 mm vs 16.9 +/- 2.8 mm, P = .22; RPV-2, 13.2 +/- 2.0 mm vs 11.8 +/
      1.6 mm, P = .22; and LPV, 12.2 +/- 2.4 mm vs 11.2 +/- 1.9 mm, P = .30). Left
      atrial function and pulmonary venous flow velocities were unchanged. Tissue
      sections determined transmurality in 93% of cryoclamp lesions and 84% of linear
      ablations performed with the 10-cm malleable probe. CONCLUSIONS: Epicardial
      application of this cryoclamp device on the beating heart produced transmural
      lesions, which persisted 30 days. Linear epicardial cryoablation was not as
      effective as the cryoclamp device at producing consistent transmural lesions.
      This novel, versatile device may be useful in treating patients with atrial
      fibrillation on the beating heart without cardiopulmonary bypass.

PMID- 16434272
TI  - Current outcomes and risk factors for the Norwood procedure.
AB  - OBJECTIVE: Tremendous strides have been made in the outcomes for hypoplastic left
      heart syndrome and other functional single-ventricle malformations over the past
      25 years. This progress relates primarily to improvements in survival for
      patients undergoing the Norwood procedure. Previous reports on risk factors have
      been on smaller groups of patients or collected over relatively long periods of
      time, during which management has evolved. We analyzed our current results for
      the Norwood procedure with attention to risk factors for poor outcome. METHODS: A
      single-institution review of all patients undergoing a Norwood procedure for a
      single-ventricle malformation from May 1, 2001, through April 30, 2003, was
      performed. Patient demographics, anatomy, clinical condition, associated
      anomalies, operative details, and outcomes were recorded. RESULTS: Of the 111
      patients, there were 23 (21%) hospital deaths. Univariate analysis revealed
      noncardiac abnormalities (genetic or significant extracardiac diagnosis, P =
      .0018), gestational age (P = .03), diagnosis of unbalanced atrioventricular
      septal defect (P = .017), and weight of less than 2.5 kg (P = .0072) to be
      related to hospital death. On multivariate analysis, only weight of less than 2.5
      kg and noncardiac abnormalities were found to be independent risk factors.
      Patients with either of these characteristics had a hospital survival of 52%
      (12/23), whereas those at standard risk had a survival of 86% (76/88).
      CONCLUSIONS: Although improvements in management might have lessened the effect
      of some of the traditionally reported risk factors related to variations in the
      cardiovascular anatomy, noncardiac abnormalities and low birth weight remain as a
      future challenge for the physician caring for the patient with single-ventricle
      physiology.

PMID- 16434273
TI  - Influence of surgical strategies on outcome after the Norwood procedure.
AB  - OBJECTIVE: The study objective was to identify how the evolution of surgical
      strategies influenced the outcome after the Norwood procedure. METHODS: From 1992
      to 2004, 367 patients underwent the Norwood procedure (median age, 4 days). Three
      surgical strategies were identified on the basis of arch reconstruction and
      source of pulmonary blood flow. The arch was refashioned without extra material
      in group A (n = 148). The arch was reconstructed with a pulmonary artery
      homograft patch in groups B (n = 145) and C (n = 74). Pulmonary blood flow was
      supplied by a modified Blalock-Taussig shunt in groups A and B. Pulmonary blood
      flow was supplied by a right ventricle to pulmonary artery conduit in group C.
      Early mortality, actuarial survival, and freedom from arch reintervention or
      pulmonary artery patch augmentation were analyzed. RESULTS: Early mortality was
      28% (n = 102). Actuarial survival was 62% +/- 3% at 6 months. Early mortality was
      lower in group C (15%) than group A (31%) or group B (31%; P <.05). Actuarial
      survival at 6 months was better in group C (78% +/- 5%) than group A (59% +/- 5%)
      or group B (58% +/- 4%; P <.05). Fifty-three patients (14%) had arch
      reintervention. Freedom from arch reintervention was 76% +/- 3% at 1 year, with
      univariable analysis showing no difference among groups A, B, and C (P =.71). One
      hundred patients (27%) required subsequent pulmonary artery patch augmentation.
      Freedom from patch augmentation was 61% +/- 3% at 1 year, and was lower in group
      C (3% +/- 3%) than group A (80% +/- 4%) or group B (72% +/- 5%; P <.05).
      CONCLUSIONS: Survival after the Norwood procedure improved after the introduction
      of a right ventricle to pulmonary artery conduit, but a greater proportion of
      patients required subsequent pulmonary artery patch augmentation. The type of
      arch reconstruction did not affect the incidence of arch reintervention.

PMID- 16434274
TI  - Robotically assisted perventricular closure of perimembranous ventricular septal
      defects: preliminary results in Yucatan pigs.
AB  - OBJECTIVE: Robotic systems allow surgeons to perform minimally invasive cardiac
      surgery in adults. Experience in the pediatric population, however, is limited.
      Perventricular closure of muscular ventricular septal defects has been reported
      in humans but requires a median sternotomy. The objective of this study was to
      assess the feasibility of robotically assisted closure of perimembranous
      ventricular septal defects by using the perventricular approach. METHODS: The
      procedure was attempted in 7 pigs with naturally occurring perimembranous
      ventricular septal defects. Echocardiography was performed to confirm the
      presence and assess the size of the defect. A 3-armed da Vinci system consisting
      of two 8-mm instrument ports and a 12-mm endoscopy port was used. A
      pericardiotomy was performed, and the right ventricular free wall was visualized.
      A spinal needle was advanced into the right ventricular cavity. By using
      echocardiographic guidance, a glide wire was advanced through the angiocatheter
      and manipulated through the defect into the left ventricle or the ascending
      aorta. A delivery sheath was advanced over the wire. An appropriately sized
      Amplatzer device was deployed through the sheath. RESULTS: The procedure was
      successful in 5 pigs. One device was removed because it was smaller than the
      defect and an appropriately sized device was not available. The placement failed
      in the second pig in the series. Four pigs were followed up for 1 to 4 months.
      Angiograms performed before the pigs were killed documented complete occlusion in
      3 and mild-to-moderate shunt in 1. CONCLUSIONS: Robotically assisted
      perventricular closure with the Amplatzer Membranous VSD Occluder is feasible.
      This approach avoids the associated morbidities of cardiopulmonary bypass and
      median sternotomy. Further investigation and refinements are needed, however,
      before application of this approach in humans.

PMID- 16434275
TI  - Diagnosis and outcome in congenital ventricular diverticulum and aneurysm.
AB  - OBJECTIVE: True congenital ventricular diverticulum and aneurysm in children are
      very uncommon. We report our experience to clarify the diagnosis and outcome of
      these little-known entities. METHODS: Twenty-two patients with congenital
      ventricular outpouchings were identified in our database from 1973 to 2004.
      Morphologic characteristics (localization, connection to a ventricle,
      contractility), histologic findings, and cardiac and/or extracardiac
      abnormalities were analyzed in all 22 patients. Cardiovascular events and
      clinical courses were reviewed. RESULTS: Congenital ventricular diverticula (n =
      16) were characterized by synchronal contractility and three myocardial layers on
      histologic examination. Two categories of congenital ventricular diverticulum
      could be identified with regard to their localization: apical and nonapical.
      Apical diverticula (n = 8) were always associated with midline thoracoabdominal
      defects and other heart malformations. Nonapical diverticula (n = 8) were always
      isolated defects. Congenital ventricular aneurysms (n = 6) were characterized by
      akinesis with paradoxical systolic motion, wide connection to the ventricle,
      fibrosis on histologic examination that appeared with high signal on T2 weighted
      magnetic resonance imaging, and absence of other heart or midline
      thoracoabdominal defects. The outcome was different in these two types of
      outpouchings: congential ventricular aneurysms were associated with adverse
      outcomes whereas the prognosis for congenital ventricular diverticula was good.
      CONCLUSION: Congenital ventricular diverticulum and aneurysm are two distinct
      entities, with different histologic and morphologic characteristics and outcomes.
      Assessment of these differential characteristics is of importance for prenatal
      counseling.

PMID- 16434276
TI  - Laparoscopic fundoplication in patients with end-stage lung disease awaiting
      transplantation.
AB  - OBJECTIVE: There is a strong association between reflux and end-stage lung
      disease, especially idiopathic pulmonary fibrosis. The presence of reflux after
      lung transplantation might predispose to the development of bronchiolitis
      obliterans. We evaluated the risk and physiologic effect of laparoscopic
      fundoplication in patients on the lung transplant waiting list. METHODS: One
      hundred forty-nine patients on the lung transplant waiting list between March
      2001 and January 2005 were evaluated. Nineteen were found to have a history of
      reflux, continued symptoms, and severe reflux by means of pH and manometric
      studies and underwent laparoscopic fundoplication. The postoperative course of
      these 19 patients, including lung function, was retrospectively reviewed.
      Postoperatively, the lung function of the 14 patients with idiopathic pulmonary
      fibrosis who underwent the laparoscopic Nissen procedure was compared with that
      of 31 patients with idiopathic pulmonary fibrosis on the transplant waiting list
      who did not undergo fundoplication. RESULTS: There were no perioperative
      complications and no decrease in lung function over the 15-month average follow
      up. Exercise capacity remained stable, as determined on the basis of 6-minute
      walk distance. Patients with idiopathic pulmonary fibrosis treated with
      fundoplication had stable oxygen requirements, whereas control patients with
      idiopathic pulmonary fibrosis on the waiting list had a statistically significant
      deterioration in oxygen requirement. CONCLUSIONS: Laparoscopic fundoplication can
      be performed safely in patients with end-stage lung disease awaiting lung
      transplantation. Overall, these patients maintained stable lung function during
      the follow-up period. When compared with a control group of patients with
      idiopathic pulmonary fibrosis not undergoing fundoplication, there was
      stabilization of oxygen requirement. A larger prospective trial evaluating the
      effect of laparoscopic fundoplication on underlying lung function in this patient
      population is warranted.

PMID- 16434277
TI  - Duration of inotropic support after left ventricular assist device implantation:
      risk factors and impact on outcome.
AB  - OBJECTIVES: Because duration of inotropic support after left ventricular assist
      device implantation has been recognized as a surrogate for right ventricular
      dysfunction, we sought to (1) identify its preimplantation risk factors,
      particularly its association with preimplantation right ventricular dysfunction,
      and (2) assess its impact on clinical outcomes. METHODS: Between 1991 and 2002,
      left ventricular assist devices were implanted in 207 patients, exclusive of
      those receiving preoperative mechanical circulatory support, which precluded
      measuring right ventricular stroke work. Duration of inotropic support was
      analyzed as a continuous variable, truncated by death or transplantation, and in
      turn as a risk factor for these 2 events. RESULTS: Inotropic support decreased
      from 100% on the day of implantation to 57%, 33%, and 22% by days 7, 14, and 21.
      Its duration was strongly associated with lower preimplantation right ventricular
      stroke work index, older age, and nonischemic cardiomyopathy and was associated
      (P < .04) with higher mortality before transplantation but not with transition to
      transplantation. We identified no preimplantation risk factors for right
      ventricular assist device use because of its relatively infrequent use in this
      population (18 patients, only 4 of whom survived to transplantation). CONCLUSION:
      Duration of inotropic support after left ventricular assist device insertion is
      strongly correlated with low preimplantation right ventricular stroke work index.
      In turn, it was associated with reduced survival to transplantation. Thus, right
      ventricular stroke work measured before implantation might be useful in decision
      making for biventricular support, destination therapy, or total artificial heart.

PMID- 16434279
TI  - Traumatic rupture of a right aortic arch in a patient with an aberrant left
      subclavian artery.

PMID- 16434278
TI  - Impact on outcomes after listing and transplantation, of a strategy to accept ABO
      blood group-incompatible donor hearts for neonates and infants.
AB  - BACKGROUND: Recent data suggest that ABO blood group-incompatible donor hearts
      are immunologically well tolerated in infants undergoing transplantation.
      METHODS: Competing-risks methodology was used to assess outcomes after listing
      and the impact of a strategy to accept heart grafts from any blood group donor
      for infants less than 18 months of age. RESULTS: From 1992 to 2002, there were 91
      listing episodes in 84 patients (including 20 fetuses; 50% were male and 63% had
      congenital heart disease). Beginning in 1995, a strategy to accept ABO
      incompatible organs was adopted. Competing-risks analysis showed that after 20
      months 60% underwent transplantation, 18% died, and less than 1% were still
      listed; the remaining 21% were de-listed because of a change of surgical strategy
      (9%), improved clinical condition (8%), and deterioration to ineligibility (4%).
      Risk factors for transplantation included only a strategy to accept ABO
      incompatible organs (P <.001). Risk factors for death included failure to accept
      ABO-incompatible organs (P =.002) and Canadian listing status 3 (P =.085) or 4 (P
      <.001). Multivariable parametric models were used to create competing risk
      predictions for outcomes specific to status and ABO-incompatible strategy. Higher
      status resulted in greater mortality regardless of strategy, although for any
      status, more patients underwent transplantation and fewer died using a strategy
      to accept ABO-incompatible organs. Parametric modeling of time-related freedom
      from death or retransplantation demonstrated no significant difference at 4 years
      posttransplantation (P =.78) for ABO-incompatible (74%) versus ABO-compatible
      transplants (72%). CONCLUSIONS: A strategy to accept ABO-incompatible donor
      hearts for infant transplantation significantly improves the likelihood of
      transplantation and reduces waiting list mortality while not adversely altering
      outcomes after transplantation.

PMID- 16434280
TI  - Complete myocardial revascularization and Dor technique in a case of left lung
      agenesis.

PMID- 16434281
TI  - Robotic endoscopic excision of accessory mitral leaflet.

PMID- 16434282
TI  - Neonatal stenotic Ebstein's anomaly: a novel technique of right ventricular
      exclusion.

PMID- 16434283
TI  - Combined atrial arterial switch operation (double switch) for hearts with Shone
      syndrome and pulmonary hypertension.

PMID- 16434284
TI  - Bifid cardiac apex: a rare morphologic structure.

PMID- 16434285
TI  - A novel aortic arch reconstruction method for double-inlet left ventricle with
      interrupted aortic arch and restrictive bulboventricular foramen.

PMID- 16434286
TI  - Repair of symptomatic neoaortic aneurysm after third-stage palliation for
      hypoplastic left heart syndrome.

PMID- 16434287
TI  - Delayed cardiac tamponade by iatrogenic aortic perforation with pacemaker
      implantation.

PMID- 16434288
TI  - Type A aortic dissection: new surgical strategy using intra-operative stenting.

PMID- 16434289
TI  - Inflow occlusion pulmonary embolectomy in the modern era of cardiac surgery.

PMID- 16434290
TI  - A primary aortoesophageal fistula due to esophageal carcinoma successfully
      treated with endoluminal aortic stent grafting.

PMID- 16434292
TI  - Superior vena cava replacement for lung cancer using a heterologous (bovine)
      prosthesis: preliminary results.

PMID- 16434291
TI  - An alternative method for the removal of thoracic esophagus without thoracotomy.

PMID- 16434293
TI  - Esophageal schwannoma.

PMID- 16434294
TI  - Fatal giant cell myocarditis after thymoma resection in myasthenia gravis.

PMID- 16434295
TI  - Using Surgicel to buttress the staple line in lung volume reduction surgery for
      chronic obstructive pulmonary disease.

PMID- 16434296
TI  - Long-term survival after excision of a solitary esophageal cancer brain
      metastasis.

PMID- 16434297
TI  - Video-assisted thoracic surgery lung resection after endobronchial valve
      placement.

PMID- 16434298
TI  - Internal thoracic vein aneurysm presenting as an anterior mediastinal mass.

PMID- 16434299
TI  - Aortic annuloplasty and valve-sparing root replacement: details of the primary
      suture line.

PMID- 16434300
TI  - Surgical management of pulmonary embolism.

PMID- 16434303
TI  - Assumed oxygen consumption in the determination of cardiac output: assume
      carefully...

PMID- 16434304
TI  - Triiodothyronine in neonatal heart surgery: Looking for an answer.

PMID- 16434306
TI  - A new modeling for each population.

PMID- 16434308
TI  - Linking gene expression, nuclear factor kappa B, remote ischemic preconditioning,
      and transplantation: a quest for an elusive Holy Grail or a road to an amazing
      discovery?

PMID- 16434309
TI  - From mesothelioma to cardiovascular protection via the phosphoinositide-3 kinase
      pathway: a new vista in cardiothoracic surgery.

PMID- 16434311
TI  - Distribution of breakpoints on chromosome 18 in breast, colorectal, and
      pancreatic carcinoma cell lines.
AB  - Chromosome 18 is frequently rearranged in carcinomas. We explored the
      distribution of breakpoints affecting chromosome 18 by mapping 56 breakpoints in
      26 carcinoma cell lines by fluorescence in situ hybridization (FISH) using
      bacterial artificial chromosomes (BACs) and band paints. The distribution of
      breaks among 18 intervals of chromosome 18 was significantly nonrandom. The
      interval spanning the centromere contained the greatest number of breaks and had
      the highest average copy number of any interval. There was a high density of
      breaks close to the centromere as well as actually within the centromere. A
      cluster of breaks encompassing SMAD4 was associated with the minimum average copy
      number, consistent with SMAD4 being a tumor suppressor gene. There may be another
      cluster of breaks around 18q12. We offer two interpretations of the concentration
      of breaks near the centromere. It may reflect selection for an oncogene near the
      centromere, or there may be an underlying bias of breakage toward the centromere.
      We show that the latter is predicted by a simple model that invokes random
      breakage following anchorage of some random point on the chromosome, or selection
      of breaks proximal to one of several tumor suppressor genes.

PMID- 16434312
TI  - Cytogenetic anomalies in hyaline vascular Castleman disease: report of two cases
      with reappraisal of histogenesis.
AB  - The pathogenesis of hyaline vascular Castleman disease (HVCD) is poorly
      understood. Although generally considered reactive in nature, a subset of cases
      has been shown to harbor focal proliferations of stromal cells, such as
      follicular dendritic cell (FDC) and angiomyoid proliferations. We report two
      typical cases of HVCD with cytogenetic anomalies: one was t(1;22)(qter;q13) and
      the other was t(7;8)(q37.3;q12) in cultured stromal cells, as demonstrated by
      conventional cytogenetic analysis. The cultured cells were immunoreactive for
      smooth muscle actin but negative for CD21, CD31, and CD34, and ultrastructurally
      possessed thin filaments (5-7.5 nm) with dense bodies, and pinocytotic vesicles,
      characteristic of smooth muscle cells. The lack of monoclonality of lymphoid
      cells in lesional tissues by immunohistochemical and molecular analyses also
      supports the origin of these anomalies from the stromal cells, most likely myoid
      cells. Moreover, the absence of overt stromal proliferations suggests that
      cytogenetic changes in stromal cells of HVCD precede histologic evidence of
      stromal overgrowth, which may account for the occurrence of angiomyoid
      proliferations arising in some cases of HVCD. Further studies with more cases are
      needed to decipher whether part or even most of HVCD cases bear genetic changes
      in the beginning of the disease without morphologically stromal overgrowth.

PMID- 16434313
TI  - Molecular and phenotypic analysis of Philadelphia chromosome-positive bilineage
      leukemia: possibility of a lineage switch from T-lymphoid leukemic progenitor to
      myeloid cells.
AB  - The occurrence of acute bilineage leukemia is thought to be the malignant
      transformation of a myeloid or lymphoid leukemic progenitor with the potential to
      differentiate into the other lineages; however, the mechanisms of this lineage
      switch are not well understood. Here, we report on the extremely rare case of
      adult Philadelphia chromosome-positive acute bilineage leukemia, which is
      characterized by T-cell acute lymphoblastic leukemia and acute myelomonocytic
      leukemia. Chromosome analysis showed 46,XY,del(7)(p11.2),t(9;22)(q34;q11.2) in
      all metaphases and a minor BCR/ABL chimeric gene was detected in these leukemic
      cells by PT-PCR. When the CD5+ and CD5- cells were sorted, a fusion gene of
      BCR/ABL and the same clonally rearranged band of a T-cell receptor (TCR) gene
      were detected in both populations. Nucleotide sequencing of the TCR-gamma gene
      revealed the clonal rearrangement of the V8-JGT2 complex in both populations.
      Overexpression of PU.1, which plays a fundamental role in myelomonocyte
      development, was found in the sorted CD34+CD7+ and CD5-, but not CD5+ cells.
      These results suggest that leukemic progenitor cells in the T-lineage with the
      del(7) and t(9;22) have the potential to differentiate into myeloid lineage, and
      that enforced PU.1 expression may contribute in part of this phenomenon.

PMID- 16434314
TI  - Coexistence of Philadelphia chromosome positive cells with and without der(9)
      deletion in a patient with chronic myelogenous leukemia.
AB  - Recently, large deletions adjacent to the Philadelphia (Ph) translocation
      breakpoint on the derivative chromosome 9 have been reported to be found in a
      substantial number of patients with chronic myelogenous leukemia (CML). The
      existence of der(9) deletion is reported as a powerful indicator of a poor
      prognosis. So far, der(9) deletion is considered to be generated when the Ph
      translocation occurs, because when der(9) deletion is found, it is detected in
      all the Ph-positive (Ph+) cells of a particular CML patient. On FISH examination
      of 47 Vietnamese CML patients, we found 11 patients carrying der(9) deletion.
      Among these, two patients harbored Ph+ metaphase cells with der(9) deletion and
      also Ph+ cells without it. In CML patients with der(9) deletion, reportedly no
      ABL/BCR transcript is detected. In these two patients, the proportion of Ph+
      cells without der(9) deletion was much smaller than that of the cells with der(9)
      deletion. Nevertheless, we detected a ABL/BCR (1b-b4) transcript in the two
      patients. This is further evidence for the existence of Ph+ cells without der(9)
      deletion. It is possible that in some CML patients, der(9) deletion is generated
      in the progression of the disease.

PMID- 16434315
TI  - Frequencies and characterization of cytogenetically unrelated clones in various
      hematologic malignancies: seven years of experiences in a single institution.
AB  - Cytogenetically unrelated clones are uncommon findings in hematologic disorders.
      In the present study, among the 1,110 various hematologic malignancies analyzed
      during the past seven years, 27 (2.4%) patients had karyotypically unrelated
      clones: 3.5% (7/202) of acute myeloid leukemias, 5.3% (11/206) of myelodysplastic
      syndromes, none of 40 acute lymphoblastic leukemias, 0.4% (1/233) of
      myeloproliferative disorders, and 2.6% (8/306) lymphoproliferative disorders with
      clonal chromosomal abnormalities. Twenty-five patients showed two unrelated
      clones and two had three unrelated clones. The most consistent chromosome
      abnormalities were del(5q) (seven cases), +8 (six cases), del(20q) (five cases),
      and del(7q), +12, +21, and -22 (three cases each). Of interest, the high
      frequency of different numeric or structural abnormalities affecting the same
      chromosomes in such clones supports the hypothesis that these karyotypically
      unrelated clones originate from the common malignant clone through submicroscopic
      molecular genetic changes and evolutionary processes.

PMID- 16434317
TI  - Complex rearrangements involving der(8)t(8;20) and der(14)t(8;14)t(11;14), CCND1,
      and duplication of IgH constant region in acute plasmablastic leukemia.
AB  - We report on a rapidly fatal case of acute plasmablastic leukemia in a 72-year
      old male from The Ukraine, who was 70 km away from Chernobyl at the time of the
      atomic accident in 1986. Spectral karyotyping and fluorescence in situ
      hybridization (FISH) studies of a bone marrow sample obtained at diagnosis
      revealed a hypodiploid karyotype with 45 chromosomes and two novel complex
      rearrangements, der(8)t(8;20)(p11.2;p?12) and
      der(14)t(8;14)(p?;p11.2)t(11;14)(q13;q32), with juxtaposition of CH (constant
      region of IgH) sequences to the oncogene CCND1 (translocated to 14q32). FISH
      analysis demonstrated that the CH on the der(14) was duplicated.

PMID- 16434316
TI  - Distribution of the alleles at loci D16S539, D7S820, and D13S317 in hydatidiform
      mole genome from Chinese women and its relationship with clinical prognosis.
AB  - Using polymerase chain reaction and denaturating polyacrylamide gel
      electrophoretic techniques, we studied 53 cases of hydatidiform moles. Of these,
      41 cases were genetically complete hydatidiform moles (g-CHM) whose genome were
      totally paternally derived. We investigated the distribution of the alleles in
      the short tandem repeat sequences at loci D16S539, D7S820, and D13S317 in these
      cases. In particular, we analyzed the allelic distribution and potential
      significance in cases with traceable benign and invasive moles (i.e., persistent
      trophoblastic tumor [PTT]). Among 41 g-CHM cases, there were six alleles at
      D16S539, five alleles at D7S820 (the frequencies of alleles 9 and 10 were
      respectively lower and higher than those in Beijing population), and seven
      alleles at D13S317; the heterozygosity of loci D16S539, D7S820, and D13S317 was
      0.0732, 0.0976, and 0.0732, respectively. Among 23 benign cases, there were six
      alleles at D16S539, four at D7S820, and six at D13S317; among 11 PTT cases, there
      were five alleles at D7S820 and four alleles each at D16S539 and D13S317. The
      frequencies of allele 9 at D16S539 and allele 10 at D7S820 were higher than in
      benign cases (P < 0.05). There were significant differences in frequencies of
      alleles 9 and 10 at D7S820 between the cases and the Beijing population, and
      heterozygosity at the three loci was lower in the cases than in the population.
      In addition, invasiveness of hydatidiform mole correlated to the frequency of
      allele 9 at loci D16S539 and allele 10 at D7S820.

PMID- 16434318
TI  - Common pattern of unusual chromosome abnormalities in hereditary papillary renal
      carcinoma.
AB  - In this study, we summarized cytogenetic and comparative genomic hybridization
      (CGH) results, mutation analysis of the MET gene, and immunohistochemistry
      results of tumors from three patients in the same family who were affected by
      hereditary papillary renal carcinoma (HPRC). All three patients showed germline
      mutations in the tyrosine kinase domain of the MET proto-oncogene, and developed
      bilateral and multiple papillary renal tumors. DNA mutation analysis showed an
      increased dosage of the mutant allele in six tumors from two patients but not in
      two tumors from the third patient. In addition to the recurrent chromosomal
      alterations found in papillary renal carcinomas, cytogenetic analyses revealed
      the presence of an identical chromosomal translocation, t(2;15)(q13;p11), in two
      different tumors from the same patient. Moreover, the same pattern of autosomal
      trisomies (+7, +12, +13, +17) was detected by CGH analysis in tumors from
      different siblings. Taking into account that the presence of an identical
      structural chromosomal aberration in two tumors and the gain of chromosome 13 are
      unusual chromosomal changes in this type of tumor, we can conclude that our
      results confirm those of other authors and suggest that the genetic
      predisposition to HPRC might predispose the acquisition of genomic alterations in
      specific chromosomes or chromosomal regions.

PMID- 16434319
TI  - Genetic analysis of human milk by fluorescence in situ hybridization.
AB  - Ductal lavage is a technique for early breast cancer detection in high-risk
      women. During this procedure, exfoliated epithelial cells are flushed out of the
      milk ducts of nonlactating women and the collected cells are analyzed for
      cellular changes associated with breast cancer. A recently developed protocol
      uses interphase fluorescence in situ hybridization (I-FISH) to detect specific
      chromosomal aneusomies known to be associated with breast cancer. The ability to
      perform I-FISH on breast milk will prove to be valuable to lactating women who
      are at high risk for breast cancer or who develop symptoms while breastfeeding.
      Using established protocols for analyzing peripheral blood lymphocytes,
      amniocytes, and epithelial cells in urine and breast duct lavage samples as a
      guide, a protocol for I-FISH of human breast milk has been developed. Cell
      isolation, fixation, pretreatment, denaturation, hybridization, and washings were
      optimized to produce slides of high quality, sensitivity, and specificity.

PMID- 16434320
TI  - Isochromosome 7q in Down syndrome.
AB  - Isochromosome 7q is not an uncommon chromosomal abnormality. It has been reported
      in association with Shwachman-Diamond syndrome, Wilms tumor, and hepatosplenic T
      cell lymphoma. In other hematolymphoid malignancies, it occurs almost invariably
      as a secondary change. A notable example is its association with t(4;11)(q21;q23)
      in acute lymphoblastic leukemia. It has rarely been described in myelodysplastic
      syndrome and acute myeloid leukemia. We report the occurrence of i(7q) as the
      primary abnormality in a 2-year-old boy with Down syndrome and minimally
      differentiated acute myeloid leukemia.

PMID- 16434321
TI  - Cutaneous aneurysmal fibrous histiocytoma with a t(12;19)(p12;q13) as the sole
      cytogenetic anomaly.
AB  - We report a case of a 39-year-old woman with a recurrent aneurysmal fibrous
      histiocytoma of the right lower leg. Cytogenetic analysis of the tumor specimen
      disclosed a 46,XX,t(12;19)(p12;q13) karyotype. Multicolor fluorescence in situ
      hybridization (M-FISH), followed by conventional FISH analysis, confirmed the
      reciprocal translocation as the sole cytogenetic anomaly, and allowed for the
      positioning of chromosomes 12 and 19 breakpoints proximal to the BCL3 gene and
      between ETV6 and PIK3C2G gene loci, respectively. Our case highlights the
      importance of distinguishing this recurrent but benign lesion from similarly
      appearing malignant skin tumors. Cytogenetic analysis may contribute to the
      diagnosis of this uncommon but distinctive clinicopathological entity.

PMID- 16434322
TI  - Two neurofibromatosis type 1 cases associated with rhabdomyosarcoma of bladder,
      one with a large deletion in the NF1 gene.
AB  - Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder,
      affecting approximately 1 in 3,500 individuals worldwide. Mutations of the NF1
      tumor suppressor gene predispose individuals to a variety of benign and malignant
      tumors. Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma and
      is also a rare tumor type in NF1 patients. We report two cases of NF1 with RMS.
      The first is that of an infant with overlapping phenotypic features of NF1 and
      Noonan syndrome (NS) who presented with RMS of the bladder. The second infant
      likewise exhibited NF1 features and was also associated with bladder RMS. DNA
      samples were extracted from peripheral blood and tumor tissue samples. We
      performed loss of heterozygosity (LOH) analysis of the NF1 gene by using seven
      intragenic markers (IVS27AAAT2.1, IVS27EVI-20, IVS27AC24.8, IVS27AC28.4, M98509,
      IVS27AC33.1, IVS38TG53.0) and one extragenic polymorphic marker (3'NF1). A large
      deletion was detected in the NF1 gene in the NF1-Noonan syndrome (NF-NS) case
      associated with RMS.

PMID- 16434323
TI  - Genotoxicity of etoposide: greater susceptibility of MLL than other target genes.
AB  - The ability of topoisomerase 2 inhibitors to induce DNA breakage is well
      recognized. Previous studies, however, have concentrated on the effects on
      individual genes. The effects of etoposide on the MLL, RUNX1, and MLLT3 genes
      were simultaneously studied in the same hemopoietic cell population. We found MLL
      to be more susceptible to etoposide-induced cleavage than RUNX1 and MLLT3, with
      maximum cleavage at a lower drug concentration. A higher level of MLL than other
      gene cleavage was also detected after cellular exposure to all drug
      concentrations. Greater susceptibility to topoisomerase 2 inhibitor-induced
      cleavage may explain the more frequent involvement of MLL in treatment-related
      leukemogenesis.

PMID- 16434325
TI  - The p53/Mdm2/p14ARF cell cycle control pathway genes may be inactivated by
      genetic and epigenetic mechanisms in gliomas.

PMID- 16434324
TI  - A case report of a patient with microcephaly, facial dysmorphism, mitomycin-c
      sensitive lymphocytes, and susceptibility to lymphoma.
AB  - We report on a 17-year-old boy with a unique lymphocyte mitomycin-C (MMC)
      sensitive chromosomal breakage syndrome. He had failure to thrive, and has
      microcephaly, slight facial dysmorphism, and constitutional short stature but no
      other phenotypic or hematological manifestations of Fanconi anemia (FA). He
      developed B-cell lymphoma of the neck, which was treated with standard doses of
      alkylating agents. Major side effects related to chemotherapy did not occur.
      Normal erythrocyte corpuscular volume, MMC-insensitive fibroblasts, and the
      occurrence of lymphoma rather than AML sets this patient apart from typical FA.
      The combination of constitutional dwarfism, microcephaly, MMC-sensitive
      lymphocytes, and susceptibility to lymphoma represents an unusual constellation
      of symptoms among genetic disorders.

PMID- 16434326
TI  - Stable integration of an empty vector in MCF-7 cells greatly alters the
      karyotype.

PMID- 16434327
TI  - Case of near triploidy with i(17)(q10) in blast crisis CML.

PMID- 16434328
TI  - Efficacy of activated charcoal administered more than four hours after
      acetaminophen overdose.
AB  - To evaluate whether administration of activated charcoal, in addition to standard
      N-acetylcysteine (NAC) therapy, after acetaminophen overdose provides additional
      patient benefit over NAC therapy alone, a 1-year non-randomized prospective,
      multi-center, observational case series was performed at three poison centers and
      one poison center system. Entrance criteria were all acute acetaminophen
      overdoses with: 1) an acetaminophen blood concentration determined to be in the
      toxic range by the Rumack-Matthew nomogram; and 2) all therapies, including NAC
      and activated charcoal, initiated between 4 and 16 h post-ingestion. There were
      145 patients meeting entrance criteria, of whom 58 patients (40%) received NAC
      only and 87 patients (60%) received NAC and activated charcoal. Overall, 23
      patients had elevations of AST or ALT greater than 1000 IU/L, of which 21
      patients received NAC only (38% of total NAC only group) and 2 patients received
      NAC and activated charcoal (2% of total NAC+AC group). Administration of
      activated charcoal in this series of patients with toxic acetaminophen
      concentrations treated with NAC was associated with reduced incidence of liver
      injury, as measured by elevated serum transaminases and prothrombin times.

PMID- 16434329
TI  - Viral load and outcome in SARS infection: the role of personal protective
      equipment in the emergency department.
AB  - This study was conducted to evaluate the effectiveness of personal protective
      equipment (PPE) against severe acute respiratory syndrome (SARS). Sixteen
      patients in a SARS cluster, including 4 health care workers (HCWs) and 12 non
      HCWs were studied. We compared the initial viral load by nasopharyngeal swabs,
      clinical progression, and outcome of this cluster. The HCWs had a lower viral
      load. The non-HCWs had a higher mean C-reactive protein, lower oxygen saturation,
      and a higher incidence of intubation and death. Secondary household transmission
      developed in three of the non-HCWs' families. One month after discharge, non-HCWs
      had more signs of fibrosis on high resolution computed tomography (HRCT) scan and
      an impaired pulmonary function test. Although most of the PPE do not confer
      absolute protection against SARS, it seems that they may lower exposure to the
      virus, leading to a lower risk of secondary transmission, and be associated with
      relatively mild disease and a better early outcome.

PMID- 16434330
TI  - Outcomes after supratherapeutic escitalopram ingestions.
AB  - Escitalopram (ESC) is a new selective serotonin reuptake inhibitor (SSRI) used in
      the treatment of depression. There are limited data regarding accidental and
      intentional ESC exposure. We conducted a retrospective chart review of isolated
      ESC ingestions reported to our regional poison center during 2003-2004. Twenty
      eight patients met inclusion criteria. The average patient age was 28.1 years
      (range 2-75 years) and the average amount of ESC ingested was 62.5 mg (range 5
      300 mg from 19 cases). The most common formulation ingested was the 20-mg tablet.
      There were eight accidental ingestions and 20 intentional overdoses. Six of the
      eight accidental ingestions were observed at home with follow-up in 24 h, and no
      adverse outcomes were reported. The other two accidental overdoses were observed
      in the Emergency Department (ED) and discharged home with no adverse events
      reported. Nineteen of the intentional overdoses were observed in the ED for
      approximately 4-6 h and discharged home or to an inpatient psychiatry ward. One
      of the intentional overdose patients was admitted for persistent lethargy, but
      had a good outcome. ESC toxicity can theoretically be life threatening, but no
      patients in our series had adverse sequealae after accidental or intentional
      overdose.

PMID- 16434331
TI  - Communication technology in trauma centers: a national survey.
AB  - The relationship between information and communication technology (ICT) and
      trauma work coordination has long been recognized. The purpose of the study was
      to investigate the type and frequency of use of various ICTs to activate and
      organize trauma teams in level I/II trauma centers. In a cross-sectional survey,
      questionnaires were mailed to trauma directors and clinicians in 457 trauma
      centers in the United States. Responses were received from 254 directors and 767
      clinicians. Communication with pre-hospital care providers was conducted
      predominantly via shortwave radio (67.3%). The primary communication methods used
      to reach trauma surgeons were manual (56.7%) and computerized group page (36.6%).
      Computerized group page (53.7%) and regular telephone (49.8%) were cited as the
      most advantageous devices; e-mail (52.3%) and dry erase whiteboard (52.1%) were
      selected as the least advantageous. Attending surgeons preferred less overhead
      paging and more cellular phone communication than did emergency medicine
      physicians and nurses. Cellular phones have become an important part of hospital
      field communication. In high-volume trauma centers, there is a need for more
      accurate methods of communicating with field personnel and among hospital care
      providers.

PMID- 16434332
TI  - Physician reporting of medically impaired drivers.
AB  - Emergency physicians frequently encounter patients whose medical conditions
      represent a risk of loss of control while driving, e.g., epilepsy and diabetes.
      In certain states, physicians are under a legal obligation to report such drivers
      to the motor vehicular authorities. To determine the uniformity of legislated
      reporting requirements for physicians caring for patients whose medical
      conditions represent an automotive hazard, we conducted a survey of Department of
      Motor Vehicles (DMV) legal departments of all the states in the United States for
      the academic year 1999-2000 regarding physician reporting of patients with
      medical conditions that might predispose them to a motor vehicle crash (MVC) and
      compared the results to a similar study done in 1986. Six (12%) of the states had
      mandatory reporting laws, 25 (49%) had permissive reporting laws, and 20 (39%)
      had no laws regarding physician reporting. There was a significant difference
      between the distribution of laws by year. There was no uniformity on a national
      level concerning such legislation.

PMID- 16434333
TI  - Serum sickness-like reactions in patients receiving intravenous infliximab.
AB  - Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) has been
      used successfully for the treatment of certain forms of Crohn's disease and
      rheumatoid arthritis. Both acute and delayed hypersensitivity reactions have been
      associated with the intravenous use of this drug. The delayed forms may present
      as a serum sickness-like illness and recognition of the clinical manifestations
      becomes crucial for early diagnosis and treatment. With the dramatic increase in
      the use of infliximab, there will likely be increased numbers of patients with
      this type of reaction. These patients may have received this drug days or even
      weeks before the clinical presentation. These types of reactions also have been
      reported with the use of other monoclonal antibodies.

PMID- 16434334
TI  - Severe hyponatremia due to desmopressin.
AB  - Nasal desmopressin (DDAVP) is a commonly prescribed antidiuretic hormone (ADH)
      analogue used for treatment of diabetes insipidus, polyuria and nocturnal
      enuresis. Although it is generally well tolerated, it can cause severe
      electrolyte imbalance. Numerous reports exist on cases of mild to moderate DDAVP
      induced hyponatremia, yet few reports describe severe hyponatremia (Na<115
      mEq/L). We present a case of a 52-year-old woman with nearly symptom-free, DDAVP
      induced hypotonic hyponatremia of 104 mEq/L following a gastrointestinal illness.
      We describe the appropriate correction of her hyponatremia and conclude by
      raising awareness of the potential for severe cases of desmopressin-associated
      hyponatremia, even in the rather symptom-free patient.

PMID- 16434335
TI  - An unstable patient with a pulsatile mass: proceed immediately to the OR?
AB  - This is a case report of a patient who presented to the Emergency Department with
      abdominal pain, unstable vital signs, and a pulsatile abdominal mass. Current
      recommendations are to limit diagnostics and send the patient to the operating
      room as soon as possible for laparotomy because even if an abdominal aortic
      aneurysm rupture is not found, most of these patients will end up having
      pathology for which surgery will ultimately be needed. This case report describes
      a patient who did not have a surgical cause for her presentation, but rather,
      severe tricuspid regurgitation and, consequently, significant pulsatile
      hepatomegaly accounting for the finding of a pulsatile abdominal mass. A brief
      overview of how such patients should be managed is presented as well as a
      recommendation that urgent bedside sonography be undertaken before proceeding to
      the operating room.

PMID- 16434336
TI  - I can hear you yet cannot comprehend: a case of pure word deafness.
AB  - This report describes a 25-year-old man with acute head trauma and brain damage
      resulting in pure word deafness. Bilateral temporal lobe pathology was confirmed
      by brain imaging and functional brain studies. A brief discussion about the
      difference between pure word deafness and other aphasias, as well as anatomic
      correlation is provided.

PMID- 16434337
TI  - Renal infarction without hematuria: two case reports.
AB  - Clinical cases of renal infarction are rarely seen and often either misdiagnosed
      or initially treated as something else. In most circumstances, renal infarctions
      are discovered accidentally, not due to a consideration of the diagnosis. A
      review of the literature reveals that we ought to search for the entity in
      patients with risk factors such as atrial fibrillation, infarction history or
      potential, mitral stenosis, infective endocarditis, atrial or ventricular septal
      defect, hypertension and ischemic heart diseases. In addition, the rise of LDH
      (lactate dehydrogenase) in serum and the presence of hematuria serves as a good
      indicator of the malady. We present two cases we encountered early this year in
      our Emergency Department. In both cases, white blood cell count and LDH showed
      significant increases, but there was no hematuria present. Both were successfully
      treated with LMWH (low-molecular-weight heparin). Upon discharge, both patients
      regained normal renal function.

PMID- 16434338
TI  - Effects of face mask ventilation in apneic patients with a resuscitation
      ventilator in comparison with a bag-valve-mask.
AB  - Bag-valve-mask ventilation in an unprotected airway is often applied with a high
      flow rate or a short inflation time and, therefore, a high peak airway pressure,
      which may increase the risk of stomach inflation and subsequent pulmonary
      aspiration. Strategies to provide more patient safety may be a reduction in
      inspiratory flow and, therefore, peak airway pressure. The purpose of this study
      was to evaluate the effects of bag-valve-mask ventilation vs. a resuscitation
      ventilator on tidal volume, peak airway pressure, and peak inspiratory flow rate
      in apneic patients. In a crossover design, 40 adults were ventilated during
      induction of anesthesia with either a bag-valve-mask device with room air, or an
      oxygen-powered, flow-limited resuscitation ventilator. The study endpoints of
      expired tidal volume, minute volume, respiratory rate, peak airway pressure,
      delta airway pressure, peak inspiratory flow rate and inspiratory time fraction
      were measured using a pulmonary monitor. When compared with the resuscitation
      ventilator, the bag-valve-mask resulted in significantly higher (mean+/-SD) peak
      airway pressure (15.3+/-3 vs. 14.1+/-3 cm H2O, respectively; p=0.001) and delta
      airway pressure (14+/-3 vs. 12+/-3 cm H2O, respectively; p<0.001), but
      significantly lower oxygen saturation (95+/-3 vs. 98+/-1%, respectively;
      p<0.001). No patient in either group had clinically detectable stomach inflation.
      We conclude that the resuscitation ventilator is at least as effective as
      traditional bag-valve-mask or face mask resuscitation in this population of very
      controlled elective surgery patients.

PMID- 16434339
TI  - ED ultrasound in hepatobiliary disease.
AB  - To evaluate the diagnostic accuracy of gallbladder ultrasound performed by
      emergency physicians (EPUS) in patients with right upper quadrant (RUQ) and
      epigastric (EPI) pain, adults>18 years of age with RUQ or EPI pain were
      prospectively evaluated by physical examination, laboratory data, and EPUS
      followed by a blinded radiology department ultrasound (RADUS). Diagnostic
      categories included: "normal gallbladder"; "uncomplicated symptomatic
      cholelithiasis" (uncomplicated SCL; stones present but symptoms and signs
      relieved and no abnormal blood-work); or "complicated symptomatic cholelithiasis"
      (CSCL; stones and positive symptoms and signs including abnormal blood-work).
      Final Emergency Department patient assessments based on the RADUS were compared
      to the EPUS. Over 2-years, 127 patients were enrolled. The sensitivity of the
      EPUS for detecting stones was 94% (positive predictive value 99%; specificity
      96%; negative predictive value 73%). In conclusion, the EPUS is a highly
      sensitive and reliable indicator of the presence of gallstones.

PMID- 16434340
TI  - Fosphenytoin may cause hemodynamically unstable bradydysrhythmias.
AB  - The prodrug fosphenytoin (FOS) was recently introduced as an alternative to
      phenytoin (PTN) and has since become a first line therapy for status epilepticus.
      Unlike PTN, FOS generally has been considered to be safe from cardiac toxicity.
      To better characterize cardiac toxicity associated with FOS administration, we
      performed a review of the Food and Drug Administration's Adverse Event Reporting
      System databank for reports of possible FOS toxicity from 1997-2002. There were
      29 applicable reports of adverse cardiac events likely related to FOS infusion,
      including 10 cardiac deaths. Among survivors, there were four cases of high-grade
      atrioventricular block, and five cases of transient sinus arrest. Our data
      suggest that FOS may produce more cardiac toxicity than previously thought.
      Clinicians should consider administering intravenous FOS in a monitored setting
      for selected high-risk patients.

PMID- 16434343
TI  - Pelvic fracture.
AB  - Pelvic fractures are common and often devastating injuries. Along with a high
      mortality, the long-term morbidity is consequential for both the individual
      patient and society. A thorough knowledge of the clinical approach will assist
      the emergency physician in providing optimal care and offer a rapid and effective
      treatment plan for life threatening hemorrhage. Using a case-based scenario, the
      initial management strategies along with rationale evidence-based treatments are
      reviewed.

PMID- 16434341
TI  - Epigastric pain.

PMID- 16434344
TI  - Subdural hematoma.

PMID- 16434345
TI  - Abdominal necrotizing fasciitis due to perforated colon cancer.

PMID- 16434346
TI  - Bag vs. machine: Where are the data?

PMID- 16434347
TI  - A child with vancomycin-induced thrombocytopenia.

PMID- 16434348
TI  - Combining clinical risk with D-dimer testing to rule out acute deep venous
      thrombosis (DVT).

PMID- 16434349
TI  - Healthy People 2010 Emergency Medicine Module: a multicenter survey and
      educational intervention.
AB  - To educate emergency medicine (EM) residents about Healthy People 2010 (HP2010),
      the nation's public health agenda. Participating EM residency programs were given
      a 40-min slide presentation and a 4-item post-test that we developed. In two
      residency programs, we conducted a "before-after" study to assess the reliability
      of the test instrument. Fifteen residencies participated, with 289 individuals
      (70% EM residents) attending the lectures. Only 19% reported any knowledge of
      HP2010 before exposure to the Module. Nevertheless, after exposure, 182 (90%)
      scored 75% or better on the four questions specifically testing the informational
      content of the Module. In the reliability study, residents showed significant
      improvement from the pre-test on both the immediate and 2-week post-tests (both
      p<0.001). In conclusion, we found that EM residents' baseline knowledge of HP2010
      was poor, and that the EM Module improved knowledge about this important public
      health document.

PMID- 16434351
TI  - Analysis and applicability of the Dutch EMS system into countries developing EMS
      systems.
AB  - Development of an Emergency Medical Services (EMS) system is a challenging task
      for administrators, government agencies, and politicians. Factors such as the
      political climate, governmental support, and monetary resources heavily influence
      and shape the development of an EMS system. There are various systems in place to
      meet the functional needs and abilities of different regions while maintaining
      the basic principle of providing fast attention to those in need, and
      transportation to a definitive care facility. In this report, we describe the
      current Dutch EMS system in Amsterdam and the methods of daily pre-hospital
      health care delivery used, while exploring its potential applicability in
      developing nations. The Dutch EMS system is a nurse-driven triage system, both at
      the dispatch level and at the treatment level. Of the approximate yearly 165,000
      calls received at the dispatch center, 40% of the requests were triaged based on
      national protocols such that no emergency ambulance dispatching was necessary.
      Furthermore, 30% of patients were treated at the scene, and did not subsequently
      require emergency transport to a definitive care facility.

PMID- 16434350
TI  - Endowed faculty positions in academic emergency medicine: where we are and where
      we need to go.
AB  - To survey academic departments of Emergency Medicine (ADEMs) in the United States
      concerning the number of endowed faculty positions, a survey was sent to the
      chairs of all 62 ADEMs in the United States belonging to the Association of
      Academic Chairs of Emergency Medicine (AACEM) as of March 1, 2004. The survey
      requested information on: the number of endowed chair and professorship
      positions; the amount required to fully fund an endowed faculty position; the
      date established; the source of funding; and if plans were in place to establish
      an endowed position. Sixty-two chairs (100%) responded. There are currently five
      endowed chair positions in four ADEMs. Twenty-eight chairs (45%) replied they are
      in the process of establishing an endowed chair; of these, six chairs (10%) have
      partially funded the position. There are four endowed professorship positions in
      three ADEMs. Twenty-one chairs (34%) are in the process of establishing an
      endowed professorship; of these, two ADEMs (3%) have partially funded the
      positions. The most common funding sources cited for these endowed positions were
      "former residents" and "friends." Nearly all chairs replied they were allowed to
      spend only 5% of the value of the endowment each year. In conclusion, there are
      currently only nine endowed faculty positions in six ADEMs in the United States.
      Another eight positions (six chairs and two professorships) are partially funded.
      Greater effort must be made in establishing more such positions in Emergency
      Medicine.

PMID- 16434352
TI  - New years resolutions and personal and professional development 2006.

PMID- 16434353
TI  - Sternocleidomastoid muscle imbalance in a patient with recurrent headache.

PMID- 16434365
TI  - Mantle cell lymphoma: from pathology and molecular pathogenesis to new
      therapeutic perspectives.

PMID- 16434364
TI  - Current therapy of sickle cell disease.

PMID- 16434366
TI  - In vitro sensitivity and cross-resistance to deoxynucleoside analogs in childhood
      acute leukemia.
AB  - BACKGROUND AND OBJECTIVES: Cytarabine (ara-C) is a key drug in the treatment of
      acute leukemia. Resistance to ara-C might be circumvented by the use of other
      deoxynucleoside analogs. DESIGN AND METHODS: Using the MTT assay, we determined
      in vitro sensitivity and cross-resistance to deoxynucleoside analogs in 362 acute
      leukemia samples from untreated children and 32 normal bone marrow mononuclear
      cell samples. RESULTS: Normal bone marrow samples were significantly more
      resistant to ara-C, cladribine and fludarabine than were acute myeloid leukemia
      (AML) samples and significantly more resistant to ara-C and fludarabine than were
      acute lymphoblastic leukemia (ALL) samples. The only drug to which AML samples
      were more sensitive in vitro than ALL was cladribine. AML FAB M5 was
      significantly more sensitive in vitro to ara-C and cladribine than FAB M1/2 or
      FAB M4. T-ALL was significantly more resistant to cladribine than B-cell
      precursor ALL. A paired analysis of 60 AML and 99 ALL samples demonstrated
      significant cross-resistance between all four deoxynucleoside analogs. Cross
      resistance was also observed between ara-C and etoposide (Rp=0.54, p<0.0001), and
      ara-C and daunorubicin (Rp=0.48, p<0.0001) in AML. In ALL blasts, cross
      resistance was observed between ara-C and vincristine (Rp=0.50; p<0.0001), and
      between ara-C and daunorubicin and L-asparaginase (Rp=0.25; p=0.01; Rp=0.28;
      p=0.005). INTERPRETATION AND CONCLUSIONS: Cladribine appears to be a useful drug
      in AML, particularly in FAB M5. We observed cross-resistance between ara-C and
      other deoxynucleoside analogs, as well as between ara-C and drugs with different
      modes of action in childhood acute leukemia.

PMID- 16434367
TI  - A pharmacological study on pegylated asparaginase used in front-line treatment of
      children with acute lymphoblastic leukemia.
AB  - BACKGROUND AND OBJECTIVES: Pegylated-asparaginase (PEG-ASP) has been
      traditionally used as a second-line preparation in children with acute
      lymphoblastic leukemia (ALL) presenting with clinical allergy to native
      asparaginase (ASP) products. The main goal of the present study was to
      investigate the pharmacological effects of the administration of PEG-ASP given as
      a first-line product in children with ALL. DESIGN AND METHODS: PEG-ASP serum
      enzymatic activity and serum and cerebrospinal fluid (CSF) levels of asparagine
      were investigated in 20 children with newly diagnosed ALL enrolled in the ongoing
      AIEOP ALL 2000 protocol and treated with PEG-ASP as a first-line ASP preparation.
      During induction the drug was administered at the dosage of 1,000 U/m2 i.v. on
      days 12 and 27. During reinduction the drug was administered only once at the
      same dosage. RESULTS: Among the 20 patients treated in induction serum PEG-ASP
      activity equalled or exceeded 100 U/L in 18/18, 11/11 and 15/18 of the samples
      available on days 22, 25 and 27, respectively, and in 16/16, 12/15 and 5/8
      samples available on days 36, 39 and 45, respectively. In the 15 patients treated
      during reinduction serum PEG-ASP activity > or =100 U/L was observed in 14/15,
      11/14, 6/10, and 0/12 samples available on days 11, 15, 18 and 23, respectively,
      after the administration of the drug. Serum asparagine levels were below the
      detection limit (< or =0.2 microM) in all patients/samples and at all time points
      evaluated during induction; during reinduction only one patient had detectable
      asparagine levels from day 11. CSF asparagine levels were below the detection
      limit of the method only in a few patients during both induction and reinduction.
      INTERPRETATION AND CONCLUSIONS: PEG-ASP given as a first-line ASP product in the
      context of an intensive chemotherapy protocol for pediatric ALL allowed adequate
      plasma enzymatic activity and asparagine depletion during both exposures to the
      drug. However, CSF asparagine depletion was inadequate.

PMID- 16434368
TI  - Pure infradiaphragmatic Hodgkin's lymphoma. Clinical features, prognostic factor
      and comparison with supradiaphragmatic disease.
AB  - BACKGROUND AND OBJECTIVES: Pure infradiaphragmatic Hodgkin's lymphoma (HL) is a
      rare disease. The prognostic impact of a purely infradiaphragmatic localization
      of this lymphoma is controversial. We aimed to evaluate the baseline
      clinicopathologic features, prognostic factors and outcome of a large series of
      consecutive patients with pure infradiaphragmatic HL. DESIGN AND METHODS: We
      analyzed 131 patients with clinical stage I/II infradiaphragmatic HL treated with
      ABVD or equivalent regimens with or without radiotherapy, and compared 54 of them
      with 444 patients with pure supradiaphragmatic disease, who were treated at the
      same center. RESULTS: Older age, clinical stage II (borderline), involvement of >
      or =3 sites, lymphocyte predominant histology, elevated serum beta2-microglobulin
      and higher International Prognostic Score were more frequent in patients with
      infradiaphragmatic disease than in those with supradiaphragmatic disease, while
      nodular sclerosis was less frequent. The complete remission rate was 100%, 97%
      and 82% for stages I, IIA and IIB, respectively. Only B-symptoms independently
      predicted for inferior failure-free survival, while inferior overall survival was
      independently associated with the involvement of > or =3 sites. At 10 years
      failure-free survival was 82+/-6% (vs. 85+/-2% for patients with
      supradiaphragmatic disease, p=0.45), overall survival was 74+/-8% (vs. 91+/-2%,
      p=0.0006), and disease-specific survival 87+/-5% (vs. 94+/-1%, p=0.04). In
      multivariate analysis the differences between infradiaphragmatic and
      supradiaphragmatic disease were obscured by older age and B-symptoms.
      INTERPRETATION AND CONCLUSIONS: Pure infradiaphragmatic HL presents with distinct
      clinicopathologic characteristics. The previously reported poorer outcome may be
      explained by the unfavorable profile of the patients rather than the
      infradiaphragmatic presentation per se. Patients with stage IIB disease should
      probably be classified as having advanced HL because of the unacceptable rate of
      primary refractory disease.

PMID- 16434369
TI  - Establishment of the MAVER-1 cell line, a model for leukemic and aggressive
      mantle cell lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Mantle cell lymphoma (MCL) cell lines are difficult to
      generate; only nine lines have been described so far and few of them have been
      thoroughly characterized. DESIGN AND METHODS: We established MAVER-1, a new MCL
      cell line, obtained from a leukemic MCL harboring both a t(11;14) translocation
      and a MYC rearrangement, and used immunohistochemistry, flow cytometry, molecular
      biology and cytogenetic techniques in order to characterize the cell line
      precisely. RESULTS: By immunohistochemistry and flow cytometry MAVER-1 displayed
      a classical MCL phenotype (IgM+, l+, CD5+, CD10-, CD19+, CD20+, CD23-, CD79a+,
      cyclin D1+) and genetic analysis showed a typical V/D/J rearrangement with naive
      mutational status. According to both classic cytogenetic analysis and spectral
      karyotyping, MAVER-1 harbored the t(11;14) translocation associated with a
      complex karyotype. Molecular analysis by polymerase chain reactions showed that
      the t(11;14) breakpoint is within the major translocation cluster. Other
      important abnormalities of MAVER-1 include TP53 gene inactivation by a combined
      mutation of exon 8 and chromosome 17p13 deletion, ATM deletion, 8q24 (MYC)
      rearrangement and 8p22 deletion. INTERPRETATION AND CONCLUSIONS: The new cell
      line will be useful for in vitro studies regarding MCL pathogenesis and drug
      sensitivity, as well as a diagnostic control material.

PMID- 16434370
TI  - In vivo T-cell immune response against anaplastic lymphoma kinase in patients
      with anaplastic large cell lymphomas.
AB  - BACKGROUND AND OBJECTIVES: Anaplastic lymphoma kinase (ALK) oncogenic fusion
      proteins, expressed in about 60% of anaplastic large cell lymphomas (ALCL), are
      tumor-specific molecular targets for such a malignancy. One of the promising ALK
      targeted therapeutic options is cancer vaccination. In this study, we investigate
      whether ALK is a tumor-associated antigen suitable for immune interventions.
      DESIGN AND METHODS: The frequency and the functional phenotype of the anti-ALK
      CD8 precursor repertoire in freshly isolated peripheral blood mononuclear cells
      (PBMC) from healthy donors and ALK-positive patients were determined by major
      histocompatibility complex (MHC)/tetrameric analyses. The anti-ALK secondary
      immune responses were evaluated as PBMC-specific interferon (INF-gamma) release
      by ELISPOT. In addition, the ability of the anti-ALK immune response to
      specifically lyse ALK-positive lymphoma cells was investigated by in vitro
      stimulation with ALK-derived peptide p280-89. RESULTS: Tetrameric MHC/peptide
      complexes revealed high frequencies of CD8/ALK-tetramer-positive cells both in
      patients and in healthy individuals. However, the functional phenotype of the
      CD8/ALK-tetramer-positive lymphocytes showed the presence of effector and memory
      T lymphocytes only in patients. The anti-ALK cytotoxic T lymphocytes (CTL) of
      patients, but not healthy donors, displayed thresholds of activation comparable
      to those of CTL precursors of a recall antigen (influenza virus). A polyclonal
      ALK-specific tumor-reactive T-cell line was isolated from patients' peripheral
      blood lymphocytes. INTERPRETATION AND CONCLUSIONS: The presence of an anti-ALK
      effector/memory lymphocyte population in the peripheral blood of ALK-positive
      patients indicates an in vivo antigenic challenge. Thus, ALK is a lymphoma
      associated antigen suitable for immune interventions. The high number of anti-ALK
      memory CD8 T cells present in patients' PBMC may represent a valid source of
      activated CTL suitable for cancer cell lysis.

PMID- 16434371
TI  - The predictive value of lipoprotein lipase for survival in chronic lymphocytic
      leukemia.
AB  - BACKGROUND AND OBJECTIVES: The mutational status of the immunoglobulin heavy
      chain variable region genes (IGVH) is a strong indicator of prognosis in B-cell
      chronic lymphocytic leukaemia (CLL). Since the determination of the IGVH mutation
      status is very labor-intensive, alternative prognostically relevant markers would
      facilitate CLL diagnostics. DESIGN AND METHODS: Ten genes were selected from
      previously published gene expression profiling studies based on their
      differential expression in IGVH mutated versus unmutated cases of CLL, and tested
      with real-time quantitative polymerase chain reaction (RQ-PCR) in unpurified
      samples from 130 CLL patients. To ascertain potential contaminating effects by
      normal hematopoietic cells, the expression levels of the selected genes were
      determined in normal monocytes, B cells, T cells, NK cells and granulocytes.
      RESULTS: The selected genes, i.e., ZAP70, LPL, SPG20, ADAM29, NRIP1, AKAP12, DMD,
      SEPT10, TPM2 and CLECSF2, showed prognostic significance. In multivariate
      logistic regression analysis expression levels of LPL, ZAP70, ADAM29 and SEPT10
      were the most predictive for IGVH mutational status. In univariate analysis the
      expression of LPL was the best predictor. For survival, expression of LPL was the
      strongest prognostic factor. In combination with the three cytogenetic markers
      associated with a poor prognosis, i.e., deletions 17p13, 11q22 and trisomy 12,
      expression of LPL and IGVH mutational status performed equally well with regard
      to their predictive value for survival, both being more predictive than ZAP70.
      INTERPRETATION AND CONCLUSIONS: This study demonstrates that LPL expression is a
      predictor for survival in CLL, and for this purpose is as good as IGVH mutational
      status and more reliable than ZAP70 expression when tested in unpurified CLL
      samples.

PMID- 16434372
TI  - An electronic tool for venous thromboembolism prevention in medical and surgical
      patients.
AB  - BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) is a complex disorder
      influenced by numerous risk factors, and occurs frequently in at-risk
      hospitalized patients. Because appropriate prevention with thromboprophylaxis is
      underused, we wanted to create an electronic tool to provide a simple risk
      assessment and suggest appropriate prophylaxis. DESIGN AND METHODS: To develop
      the risk matrix, iterative rating of odds ratios was performed for 60
      predisposing VTE risk factors, using analytical methods that account for multiple
      risk factors in a single patient and their non-independence. For exposing risk
      factors, a single score was assigned to each set of factors, both medical (25
      items) and surgical conditions (144 items). A CART regression model was used to
      integrate the risk scales into a 4-level measure of overall risk. The validity of
      the level of risk and the appropriateness of 11 different prophylactic approaches
      was assessed using the RAND/UCLA appropriateness method and validated by expert
      opinion ratings (n=1998) on sample case scenarios (n=108). RESULTS: Correlation
      between the level of risk calculated by the risk matrix and that offered by
      expert opinion for individual surgical and medical clinical cases was high (65%
      and 70%, respectively). The matrix over-estimated the level of risk, compared
      with that offered by expert opinion, in 28% and 20% of surgical and medical
      cases, respectively, but the appropriate prophylaxis suggested was no different.
      Between-expert agreement on the appropriateness of the prophylaxis
      recommendations was high (90-94% of indications). INTERPRETATION AND CONCLUSIONS:
      This computer-based electronic tool for individualized assessment of venous
      thromboembolic risk successfully identified both the perceived risk of thrombosis
      and the appropriate prophylactic approach for medical and surgical patients.

PMID- 16434373
TI  - Predicting outcomes of HLA-identical allogeneic stem cell transplants from
      variable number of tandem repeat disparity between donors and recipients.
AB  - BACKGROUND AND OBJECTIVES: Detecting differences in the variable number of tandem
      repeats (VNTR) between a recipient and a donor has already been used to monitor
      the degree of chimerism after allogeneic stem cell transplantation (SCT).
      Alongside major histocompatibility complex disparity, the disparity of various
      polymorphous proteins encoded by several genes may play a critical role in the
      pathogenesis of graft-versus-host disease (GVHD) in allogenic SCT. However, the
      biological effect of VNTR disparity has scarcely been studied. BACKGROUND AND
      OBJECTIVES: Eighty-four patients receiving an SCT from an HLA-identical sibling
      (n=68) or an unrelated donor (n=16) were analyzed. The patients were transplanted
      because of acute myeloid leukemia (ns=48), acute lymphoblastic leukemia (n=8),
      chronic myeloid leukemia (n=15), non-Hodgkin's lymphoma (n=18) and
      myelodysplastic syndrome (n=3). Polymerase chain reaction analysis was performed
      to amplify three VNTR regions (D1S80, D1S111, and D17S5). These regions were
      classified as fully matched, partially matched, or mismatched between donors
      recipients. RESULTS: A strong correlation was observed between D1S80 matching
      status and transplant outcomes in terms of overall survival (p=0.0179) and non
      relapse mortality (p=0.0305), but not for the D1S111 or D17S5 disparity. The
      fully matched D1S80 pairs showed a better overall survival (72% vs 38%) and lower
      non-relapse mortality (17% vs 50%) compared to the partially matched or
      mismatched pairs. In multivariate analyses, a fully matched D1S80 pair was found
      to be an independent favorable prognostic factor for overall survival (p=0.03)
      and non-relapse mortality (p=0.05). In addition, D1S80 disparity was
      significantly associated with the occurrence of gut chronic GVHD (p=0.05).
      INTERPRETATION AND CONCLUSIONS: The present data suggest that disparities in
      D1S80--located in chromosome 1--are associated with an increased incidence of gut
      chronic GVHD and non-relapse mortality.

PMID- 16434374
TI  - Risk factors for the development of cytomegalovirus disease after allogeneic stem
      cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) disease remains an important
      complication of allogeneic stem cell transplantation (SCT). We studied viral load
      kinetics and correlated the viral load and other transplant factors with the
      development of CMV disease. DESIGN AND METHODS: We studied 162 consecutive
      patients who were CMV seropositive or had CMV seropositive donors. Quantification
      of CMV DNA was performed by real-time polymerase chain reaction. RESULTS: CMV DNA
      detected was detected in 105 of the 162 patients. The mean peak viral loads were
      similar at first and subsequent reactivations. The serologic status of the donors
      and recipients prior to SCT significantly influenced the viral load. The
      cumulative incidence of CMV disease was 1.8% at 100 days and 6.3% at 365 days
      after SCT. The peak viral load were higher in patients who developed CMV disease
      than in patients without CMV disease (log10 3.5; SE +/- 0.26/200,000 cells vs.
      log10 2.7; SE +/- 0.09/200,000 cells; p=0.02). However, in multivariate analysis,
      only acute graft-versus-host disease (GVHD) grade II-IV and a graft from a CMV
      negative donor to a CMV-positive patient were significant risk factors for CMV
      disease. In patients who required more than one course of pre-emptive therapy,
      acute GVHD and the rate of decrease in viral load during first pre-emptive
      therapy were significant risk factors for subsequent development of CMV disease.
      INTERPRETATION AND CONCLUSIONS: A decrease in viral load during pre-emptive
      therapy is an important factor for later development of CMV disease.

PMID- 16434375
TI  - Chemotherapy-induced nausea and vomiting in acute leukemia and stem cell
      transplant patients: results of a multicenter, observational study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the incidence
      and severity of chemotherapy-induced nausea and vomiting (CINV) in oncohematology
      in routine clinical practice, its impact on quality of life, and caregivers'
      perception of the extent of the problem. DESIGN AND METHODS: This was a
      multicenter, prospective, observational follow-up study including: (i) acute
      myeloid leukemia patients treated with moderately to highly emetogenic
      chemotherapy and (ii) hematopoietic stem cell transplant recipients, without
      reduced intensity conditioning. No exclusion criteria were applied. All patients
      received at least one 5-HT3 antagonist for emesis prophylaxis. Patients recorded
      emetic episodes and rated nausea daily. Quality of life was assessed through a
      validated functional living Index-Emesis questionnaire. A survey of caregivers'
      predictions of CINV was made and the predictions then compared with the observed
      CINV. RESULTS: One hundred consecutive transplant and 77 acute myeloid leukemia
      patients were studied. Transplant conditioning was the most important risk factor
      for CINV: complete response occurred in only 20% of transplant patients (vs. 47%
      for leukemia patients). Among patients with emesis, the mean percentage of days
      with emesis and the mean (+/-SD) total number of emetic episodes were 61% and
      9.4+/-8.9 (transplant recipients), and 53.6% and 6.2+/-7.3 (leukemia patients),
      respectively. CINV control was lower in the delayed than in the acute phase.
      Antiemetic rescue therapy was ineffective. CINV had a deleterious effect on
      quality of life, especially among transplant recipients. Caregivers
      underestimated the incidence of delayed nausea and emesis in the transplant
      setting. INTERPRETATION AND CONCLUSIONS: Despite 5-HT3 antagonist prophylaxis,
      CINV remains a significant problem in oncohematology, especially in the delayed
      phase and in transplant recipients.

PMID- 16434376
TI  - Iron overload due to mutations in ferroportin.
AB  - Iron overload disease due to mutations in ferroportin has a dominant inheritance
      and a variable clinical phenotype, such that some patients show early Kupffer
      cell iron loading and low transferrin saturation, while others show hepatocyte
      iron loading and high transferrin saturation. Studies expressing ferroportin
      mutant proteins in cultured cells have shown that mutant proteins fall into two
      main classes; proteins that do not localize to the cell surface and are unable to
      export iron, and those that localize to the cell surface but are unable to
      respond to the antimicrobial peptide hepcidin. Patients with mutant ferroportin
      proteins that do not localize to the cell surface show typical ferroportin
      disease with low transferrin saturation and early Kupffer cell iron loading,
      while patients with mutant proteins unable to respond to hepcidin show high
      transferrin saturation and early hepatocyte iron loading similar to classic
      hereditary hemochromatosis. The dominant genetic transmission of ferroportin
      linked disorders is explained by the in vitro data, which suggest that
      ferroportin is a multimer and that the behavior of the mutant protein can affect
      the behavior of the wild type protein.

PMID- 16434378
TI  - Current status and perspective of antibody therapy in follicular lymphoma.
AB  - The development of antibody--based therapeutic strategies has clearly changed the
      standard clinical approach to patients with advanced stage follicular lymphoma.
      The chimeric monoclonal anti-CD20 antibody rituximab has shown high efficacy in
      previously untreated and relapsed or refractory patients. Rituximab combined with
      conventional chemotherapy is a highly attractive approach with proven synergism
      in vitro and in vivo and is widely accepted as standard treatment for advanced
      stage follicular lymphoma. Furthermore, rituximab maintenance has been shown to
      improve disease control after successful cytoreduction with rituximab as a single
      agent therapy or polychemotherapy. Additional antibodies, different target
      molecules and modified schedules are currently being evaluated in preclinical and
      clinical trials. Strategies to enhance the efficacy of antibody--based therapies
      include stimulation of innate immunity and the generation of immunotoxins and
      radioimmunoconjugates (radioimmunotherapy). Ongoing studies are evaluating the
      role of monoclonal antibodies in multimodal therapeutic approaches to further
      improve response rates and duration with the final aim of prolonging overall
      survival of patients with advanced stage follicular lymphoma.

PMID- 16434377
TI  - Management of nodal diffuse large B-cell lymphomas: practice guidelines from the
      Italian Society of Hematology, the Italian Society of Experimental Hematology and
      the Italian Group for Bone Marrow Transplantation.
AB  - The Italian Society of Hematology (SIE) and two affiliate societies (SIES and
      GITMO) commissioned a project to develop clinical practice guidelines for the
      treatment of nodal diffuse large B-cell non Hodgkin lymphomas (DLBCL). Key
      questions clinically relevant to the management of patients with nodal DLBCL were
      formulated by an Advisory Committee (AC) and approved by an Expert Panel (EP)
      composed of eight senior hematologists. After a comprehensive and systematic
      literature review, the EP formulated therapy recommendations and graded them
      according to the supporting evidence. An explicit approach to consensus
      methodologies was used for evidence interpretation and for producing
      recommendations in the absence of strong evidence. The EP formulated
      recommendations on which first-line therapy to choose in patients with nodal
      DLBCL. Patients of all ages, with stage I-II disease and no adverse prognostic
      factors should receive abbreviated chemotherapy with an anthracycline-containing
      regimen plus involved field radiotherapy (35-40 Gy). Patients with stage I-II
      disease and at least one adverse prognostic factor, or with stage III-IV disease,
      should receive frontline chemoimmunotherapy with CHOP, CHOP-like or third
      generation chemotherapy plus rituximab. Recommendations on stem cell
      transplantation and on which therapy to adopt for refractory or relapsed patients
      were also formulated.

PMID- 16434379
TI  - Radioimmunotherapy and autologous stem cell transplantation for the treatment of
      B-cell lymphomas.
AB  - Relapse continues to be the primary cause of treatment failure in patients with
      non-Hodgkin's lymphomas (NHL) undergoing high-dose therapy and autologous stem
      cell transplantation. The anti-CD20 radioimmunoconjugates, Y-90 ibritumomab
      tiuxetan (Zevalin; Biogen Idec, Inc., Cambridge, MA, USA) and I-131 tositumomab
      (Bexxar; Corixa, Seattle, WA; and Glaxo Smith Kline; Philadelphia, PA, USA) have
      been associated with high response rates, durable remissions and limited toxicity
      apart from myelosuppression, making them ideal candidates for use in
      autotransplantation. Tested first as single agents in relapsed patients with
      indolent and transformed NHL, and then at much higher doses with stem cell
      support, these agents have now been combined with high-dose chemotherapy prior to
      autologous stem cell transplant. Radioimmunoconjugates have been used to replace
      total body irradiation (TBI) in some studies and to augment standard chemotherapy
      regimens in others. Thus far the results are promising, with combinations of
      radioimmunoconjugates and chemotherapy producing long-lasting responses in high
      risk patients with no more toxicity than that caused by standard conditioning
      regimens. These results are notable in light of the fact that the dose of
      radiation delivered to the tumor is 10-fold higher than the dose achievable with
      TBI. Whether this increase in radiation dose to the targeted lymphoma translates
      into more durable remissions and an improvement in overall survival requires
      further investigation.

PMID- 16434380
TI  - Cell cycle kinetic changes induced by interleukin-3 and interleukin-6 during ex
      vivo expansion of mobilized peripheral blood CD34 cells.
AB  - The long-term repopulating capacity of mobilized peripheral blood (MPB) CD34+
      cells can be abrogated during ex vivo expansion due to cell-cycle related
      changes. In this study, we traced cell cycle kinetic and quiescent status of
      CD34+ cells during ex vivo expansion with exogenous cytokines. The addition of
      interleukin-3 (IL-3) and interleukin-6 (IL-6) to early acting cytokines resulted
      in a significantly lower percentage of cells remaining undivided or in quiescent
      G0 phase when compared to the use of early acting cytokines alone. We conclude
      that ex vivo expansion of MPB CD34+ cells with a cocktail of five cytokines
      yields a highly cycling offspring, which could impair long-term repopulating
      capacity.

PMID- 16434381
TI  - Long-term hydroxyurea treatment in children with sickle cell disease: tolerance
      and clinical outcomes.
AB  - Two hundred twenty-five SCD children have been enrolled in a study assessing the
      tolerability of hydroxyurea treatment. Mean age at inclusion was 9.2+/-4.4 years,
      median duration of treatment was 3.8 years. Ten and 75 patients have been treated
      respectively for more than 10 and 5 years. No severe side effect was related to
      hydroxyurea treatment, which was discontinued in 81 children mainly for treatment
      failure (30 cases) or non-compliance (17 cases). Treatment was also withdrawn in
      5 of 6 children who had developed hypersplenism, in 3 because of a pathological
      transcranial Doppler, and in 2 after a stroke.

PMID- 16434382
TI  - Known and new delta globin gene mutations and their diagnostic significance.
AB  - Mutations in the delta-globin gene (HBD, MIM# 142000) are not pathologically
      relevant. However, since high HbA2 levels are diagnostic for beta-thalassemia
      trait and a lowered level for an alpha- or delta-mutation, co-inheritance of
      delta- and beta-gene defects may lead to misinterpretation of diagnostic results.
      We examined 29 cases with low HbA2 level diagnosed in our laboratory, in the
      presence or absence of a second HbA2 fraction. We found a delta globin gene
      mutation in 20 cases. In total four different known mutations were found, three
      structural and one expressional. Moreover, two new defects were observed, one
      causing a structural abnormality and one a beta-thalassemia. The structural
      abnormality HBD c.431A->G (p.His144Arg)(dcd 143 CAC->CGC) was homologous to the
      beta-globin gene variant called Hb-Abruzzo and we have named this mutation HbA2 
      Abruzzo. The new delta-thalassemia defect HBD c.-118C->T (d -68 C->T) has no
      homology on the beta-globin gene (HBB, MIM# 141900). All mutations caused a low
      HbA2 level and through this could lead to misdiagnosis when inherited together
      with a beta-thalassemia.

PMID- 16434383
TI  - Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose
      dexamethasone for relapsed/refractory multiple myeloma: a prospective,
      multicenter, phase II study.
AB  - The aim of this prospective, multicenter, phase II study was to investigate the
      combination of pegylated liposomal doxorubicin (Caelyx) 40 mg/m2 on day 1 every
      28 days, dexamethasone 40 mg p.o. on days 1-4 and 9-12 and thalidomide 100 mg
      daily in 50 patients with advanced multiple myeloma. Twenty-six percent of
      patients achieved a complete response, 6% a near complete response, 6% a very
      good partial response, 38% a partial response, 16% a minor response and 8%
      progressed, for an overall response rate of 92%. The median event-free survival
      was 17 months and the median overall survival was not reached. Grade 3 non
      hematologic toxicity occurred in 12% of patients, thromboembolic disease in 12%
      and severe infection in 16%. The combination of pegylated liposomal doxorubicin,
      dexamethasone an thalidomide is safe and very effective in advanced multiple
      myeloma.

PMID- 16434384
TI  - The role of the K247R substitution in the ABL tyrosine kinase domain in
      sensitivity to imatinib.
AB  - Imatinib mesylate has become the gold standard front-line treatment of chronic
      myelogenous leukemia through its ability to inhibit ABL tyrosine kinase.
      Resistance to this inhibition may occur. We investigated the role of the K247R
      polymorphism in persistent sensitivity.

PMID- 16434385
TI  - Acute lymphoblastic leukemia in children with associated genetic conditions other
      than Down's syndrome. The AIEOP experience.
AB  - We retrospectively reviewed the databases of seven studies on acute lymphoblastic
      leukemia (ALL) by the Associazione Italiana Ematologia Oncologia Pediatrica
      (AIEOP) to identify patients with associated genetic disease, other than Down's
      syndrome. Forty-two patients were reported to have associated genetic conditions
      that included beta-thalassemia (n=10), ataxia-telangiectasia (n=5),
      neurofibromatosis (n=3), Sotos syndrome (n=2) and other individual conditions.
      Patients with ataxia-telangiectasia, all with T-cell ALL, had a higher frequency
      of adverse events.

PMID- 16434386
TI  - The role of second autografts in the management of myeloma at first relapse.
AB  - We report an analysis of the value of a second high-dose melphalan autograft,
      performed at relapse, on a series of newly diagnosed myeloma patients entered
      into the high-dose program at our center. We conclude that relapse-free survival
      after the first autograft is a major prognostic factor in determining outcome.

PMID- 16434387
TI  - Primary cutaneous CD4+/CD56+ hematodermic neoplasm (blastic NK-cell lymphoma): a
      report of five cases.
AB  - CD4+/CD56+ hematodermic neoplasm (WHO-EORTC) or blastic NK-cell lymphoma (WHO) is
      a rare aggressive (CD4+)(CD56+)lin- skin-tropic lymphoma of putative early
      plasmacytoid dendritic cell origin. We present five cases to highlight the need
      for greater awareness of this entity amongst pathologists such that aggressive
      treatment be considered given the generally poor prognosis.

PMID- 16434388
TI  - The inhibitory receptor NKG2A determines lysis of vaccinia virus-infected
      autologous targets by NK cells.
AB  - Signals transduced by inhibitory receptors that recognize self-MHC class I
      molecules prevent NK cells from being activated by autologous healthy target
      cells. In order for NK cells to be activated upon contact with an infected cell,
      the balance between the activating and inhibitory signals that regulate NK cell
      function must be altered in favor of activation. By studying liver-derived NK
      cells, we show that only a subpopulation of NK cells expressing high levels of
      the inhibitory receptor NKG2A are able to lyse autologous vaccinia-infected
      targets, and that this is due to selective down-regulation of HLA-E. These data
      demonstrate that release from an inhibitory receptor:ligand interaction is one
      mechanism that permits NK cell recognition of a virally infected target, and that
      the variegated expression of inhibitory receptors in humans generates a
      repertoire of NK cells with different antiviral potentials.

PMID- 16434389
TI  - Recombinant O-GlcNAc transferase isoforms: identification of O-GlcNAcase, yes
      tyrosine kinase, and tau as isoform-specific substrates.
AB  - O-linked N-acetylglucosaminyltransferase (OGT) catalyzes the transfer of O-linked
      GlcNAc to serine or threonine residues of a variety of substrate proteins,
      including nuclear pore proteins, transcription factors, and proteins implicated
      in diabetes and neurodegenerative disorders. We have identified two
      nucleocytoplasmic isoforms of OGT (ncOGT and sOGT) and one isoform that localizes
      to the mitochondria (mOGT). These three isoforms contain identical catalytic
      regions but differ in the number of tetratricopeptide repeat motifs found at the
      N-terminus of each enzyme. We expressed each of these OGT isoforms in a soluble
      form in Escherichia coli and have used them to identify novel targets including
      the Src-family tyrosine kinase yes and O-GlcNAc-ase. We demonstrate that some
      substrate proteins, such as Nup62 and casein kinase II, are glycosylated by both
      ncOGT and mOGT, while others such as O-GlcNAcase and tau are specifically
      modified by ncOGT. The yes kinase was specifically modified by mOGT. The short
      isoform of OGT (sOGT) did not glycosylate any of the substrates tested, although
      it retains a potentially active catalytic domain. Our findings demonstrate the
      potential utility of recombinant OGT in identifying new targets and illustrate
      the necessity to examine all active isoforms of the enzyme. The identification of
      a tyrosine kinase and O-GlcNAcase as OGT targets suggests the potential for OGT
      participation in numerous signal transduction cascades.

PMID- 16434390
TI  - Dissociation of recruitment and activation of the small G-protein Rac during
      Fcgamma receptor-mediated phagocytosis.
AB  - Rho-family proteins play a central role in most actin-dependent processes,
      including the control and maintenance of cell shape, adhesion, motility, and
      phagocytosis. Activation of these GTP-binding proteins is tightly regulated
      spatially and temporally; however, very little is known of the mechanisms
      involved in their recruitment and activation in vivo. Because of its inducible,
      restricted signaling, phagocytosis offers an ideal physiological system to
      delineate the pathways linking surface receptors to actin remodeling via Rho
      GTPases. In this study, we investigated the involvement of early regulators of
      Fcgamma receptor signaling in Rac recruitment and activation. Using a combination
      of receptor mutagenesis, cellular, molecular, and pharmacological approaches, we
      show that Src family and Syk kinases control Rac and Vav function during
      phagocytosis. Importantly, both the immunoreceptor tyrosine-based activation
      motif within Fcgamma receptor cytoplasmic domain and Src kinase control the
      recruitment of Vav and Rac. However, Syk activity is dispensable for Vav and Rac
      recruitment. Moreover, we show that Rac and Cdc42 activities coordinate F-actin
      accumulation at nascent phagosomes. Our results provide new insights in the
      understanding of the spatiotemporal regulation of Rho-family GTPase function, and
      of Rac in particular, during phagocytosis. We believe they will contribute to a
      better understanding of more complex cellular processes, such as cell adhesion
      and migration.

PMID- 16434391
TI  - Secretion of the Notch-1 Abeta-like peptide during Notch signaling.
AB  - The canonical pathway of Notch signaling is mediated by regulated intramembrane
      proteolysis (RIP). In the pathway, ligand binding results in sequential
      proteolysis of the Notch receptor, and presenilin (PS)-dependent intramembrane
      proteolysis at the interface between the membrane and cytosol liberates the Notch
      1 intracellular domain (NICD), a transcription modifier. Because the degradation
      of the Notch-1 transmembrane domain is thought to require an additional cleavage
      near the middle of the transmembrane domain, extracellular small peptides (Notch
      1 Abeta-like peptide (Nbeta)) should be produced. Here we showed that Nbeta
      species are indeed secreted during the process of Notch signaling. We identified
      mainly two distinct molecular species of novel Nbeta, Nbeta21 and C-terminally
      elongated Nbeta25, which were produced in an approximately 5:1 ratio. This
      process is reminiscent of the production of Alzheimer disease-associated Abeta.
      PS pathogenic mutants increased the production of the longer species of Abeta
      (Abeta42) from beta-amyloid protein precursor. We revealed that several Alzheimer
      disease mutants also cause a parallel increase in the secretion of the longer
      form of Nbeta. Strikingly, chemicals that modify the Abeta42 level caused
      parallel changes in the Nbeta25 level. These results demonstrated that the
      characteristics of C-terminal elongation of Nbeta and Abeta are almost identical.
      In addition, because many other type 1 membrane-bound receptors release
      intracellular domains by PS-dependent intramembrane proteolysis, we suspect that
      the release of Abeta- or Nbeta-like peptides is a common feature of the
      proteolysis during RIP signaling. We anticipate that this study will open the
      door to searches for markers of RIP signaling and surrogate markers for Abeta42
      production.

PMID- 16434392
TI  - CARMIL is a potent capping protein antagonist: identification of a conserved
      CARMIL domain that inhibits the activity of capping protein and uncaps capped
      actin filaments.
AB  - Acanthamoeba CARMIL was previously shown to co-purify with capping protein (CP)
      and to bind pure CP. Here we show that this interaction inhibits the barbed end
      capping activity of CP. Even more strikingly, this interaction drives the
      uncapping of actin filaments previously capped with CP. These activities are CP
      specific; CARMIL does not inhibit the capping activities of either gelsolin or
      CapG and does not uncap gelsolin-capped filaments. Although full-length (FL)
      CARMIL (residues 1-1121) possesses both anti-CP activities, C-terminal fragments
      like glutathione S-transferase (GST)-P (940-1121) that contain the CARMIL CP
      binding site are at least 10 times more active. We localized the full activities
      of GST-P to its C-terminal 51 residues (1071-1121). This sequence contains a
      stretch of 25 residues that is highly conserved in CARMIL proteins from protozoa,
      flies, worms, and vertebrates (CARMIL Homology domain 3; CAH3). Point mutations
      showed that the majority of the most highly conserved residues within CAH3 are
      critical for the anti-CP activity of GST-AP (862-1121). Finally, we found that
      GST-AP binds CP approximately 20-fold more tightly than does FL-CARMIL. This
      observation together with the elevated activities of C-terminal fragments
      relative to FL-CARMIL suggests that FL-CARMIL might exist primarily in an
      autoinhibited state. Consistent with this idea, proteolytic cleavage of FL-CARMIL
      with thrombin generated an approximately 14-kDa C-terminal fragment that
      expresses full anti-CP activities. We propose that, after some type of
      physiological activation event, FL-CARMIL could function in vivo as a potent CP
      antagonist. Given the pivotal role that CP plays in determining the global actin
      phenotype of cells, our results suggest that CARMIL may play an important role in
      the physiological regulation of actin assembly.

PMID- 16434393
TI  - Subclassification of the RBCC/TRIM superfamily reveals a novel motif necessary
      for microtubule binding.
AB  - The biological significance of RBCC (N-terminal RING finger/B-box/coiled coil)
      proteins is increasingly being appreciated following demonstrated roles in
      disease pathogenesis, tumorigenesis, and retroviral protective activity. Found in
      all multicellular eukaryotes, RBCC proteins are involved in a vast array of
      intracellular functions; but as a general rule, they appear to function as part
      of large protein complexes and possess ubiquitin-protein isopeptide ligase
      activity. Those members characterized to date have diverse C-terminal domain
      compositions and equally diverse subcellular localizations and functions. Using a
      bioinformatics approach, we have identified some new RBCC proteins that help
      define a subfamily that shares an identical domain arrangement (MID1, MID2,
      TRIM9, TNL, TRIM36, and TRIFIC). Significantly, we show that all analyzed members
      of this subfamily associate with the microtubule cytoskeleton, suggesting that
      subcellular compartmentalization is determined by the unique domain architecture,
      which may in turn reflect basic functional similarities. We also report a new
      motif called the COS box, which is found within these proteins, the MURF family,
      and a distantly related non-RBCC microtubule-binding protein. Notably, we
      demonstrate that mutations in the COS box abolish microtubule binding ability,
      whereas its incorporation into a nonmicrotubule-binding RBCC protein redirects it
      to microtubule structures. Further bioinformatics investigation permitted
      subclassification of the entire human RBCC complement into nine subfamilies based
      on their varied C-terminal domain compositions. This classification schema may
      aid the understanding of the molecular function of members of each subgroup and
      their potential involvement in both basic cellular processes and human disease.

PMID- 16434395
TI  - Leucine 135 of tropomodulin-1 regulates its association with tropomyosin, its
      cellular localization, and the integrity of sarcomeres.
AB  - Tropomodulin-1 (Tmod-1) is a well defined actin-capping protein that interacts
      with tropomyosin (TM) at the pointed end of actin filaments. Previous studies by
      others have mapped its TM-binding domain to the amino terminus from amino acid 39
      to 138. In this study, we have identified several amino acid residues on Tmod-1
      that are important for its interaction with TM5 (a nonmuscle TM isoform).
      Glutathione S-transferase affinity chromatography and immunoprecipitation assays
      reveal that Tmod sense mutations of either amino acid 134, 135, or 136 causes
      various degrees of loss of function of Tmod TM-binding ability. The reduction of
      TM-binding ability was relatively mild (reduced approximately 20-40%) from the
      G136A Tmod mutant but more substantially (reduced approximately 50-100%) from the
      I134D, L135E, and L135V Tmod mutants. In addition, mutation at any of these three
      sites dramatically alters the subcellular location of Tmod-1 when introduced into
      mammalian cells. Further analysis of these three mutants uncovered a previously
      unknown nuclear trafficking function of Tmod-1, and residues 134, 135, and 136
      are located within a nuclear export signal motif. As a result, mutation on either
      residue 134 or residue 135 not only will cause a significant reduction of the
      Tmod-1 ability to bind to TM5 but also lead to predominant nuclear localization
      of Tmod-1 by crippling its nuclear export mechanism. The failure of the Tmod
      mutations to fully associate with TM5 when introduced into neonatal rat
      cardiomyocytes was also associated with an accelerated and severe fragmentation
      of sarcomeric structures compared with overexpression of wild type Tmod-1. The
      multiple losses of function of Tmod engendered by these missense mutations are
      most severe with the single substitution of residue 135.

PMID- 16434396
TI  - The structural basis of signal transduction for the response regulator PrrA from
      Mycobacterium tuberculosis.
AB  - The structure of the two-domain response regulator PrrA from Mycobacterium
      tuberculosis shows a compact structure in the crystal with a well defined
      interdomain interface. The interface, which does not include the interdomain
      linker, makes the recognition helix and the trans-activation loop of the effector
      domain inaccessible for interaction with DNA. Part of the interface involves
      hydrogen-bonding interactions of a tyrosine residue in the receiver domain that
      is believed to be involved in signal transduction, which, if disrupted, would
      destabilize the interdomain interface, allowing a more extended conformation of
      the molecule, which would in turn allow access to the recognition helix. In
      solution, there is evidence for an equilibrium between compact and extended forms
      of the protein that is far toward the compact form when the protein is
      inactivated but moves toward a more extended form when activated by the cognate
      sensor kinase PrrB.

PMID- 16434394
TI  - Phospholemman inhibition of the cardiac Na+/Ca2+ exchanger. Role of
      phosphorylation.
AB  - We have demonstrated previously that phospholemman (PLM), a 15-kDa integral
      sarcolemmal phosphoprotein, inhibits the cardiac Na+/Ca2+ exchanger (NCX1). In
      addition, protein kinase A phosphorylates serine 68, whereas protein kinase C
      phosphorylates both serine 63 and serine 68 of PLM. Using human embryonic kidney
      293 cells that are devoid of both endogenous PLM and NCX1, we first demonstrated
      that the exogenous NCX1 current (I(NaCa)) was increased by phorbol 12-myristate
      13-acetate (PMA) but not by forskolin. When co-expressed with NCX1, PLM resulted
      in: (i) decreases in I(NaCa), (ii) attenuation of the increase in I(NaCa) by PMA,
      and (iii) additional reduction in I(NaCa) in cells treated with forskolin.
      Mutating serine 63 to alanine (S63A) preserved the sensitivity of PLM to
      forskolin in terms of suppression of I(NaCa), whereas mutating serine 68 to
      alanine (S68A) abolished the inhibitory effect of PLM on I(NaCa). Mutating serine
      68 to glutamic acid (phosphomimetic) resulted in additional suppression of
      I(NaCa) as compared with wild-type PLM. These results suggest that PLM
      phosphorylated at serine 68 inhibited I(NaCa). The physiological significance of
      inhibition of NCX1 by phosphorylated PLM was evaluated in PLM-knock-out (KO)
      mice. When compared with wild-type myocytes, I(NaCa) was significant larger in
      PLM-KO myocytes. In addition, the PMA-induced increase in I(NaCa) was
      significantly higher in PLM-KO myocytes. By contrast, forskolin had no effect on
      I(NaCa) in wild-type myocytes. We conclude that PLM, when phosphorylated at
      serine 68, inhibits Na+/Ca2+ exchange in the heart.

PMID- 16434397
TI  - A pathway of structural changes produced by monastrol binding to Eg5.
AB  - Monastrol is a small molecule inhibitor that is specific for Eg5, a member of the
      kinesin 5 family of mitotic motors. Crystallographic models of Eg5 in the
      presence and absence of monastrol revealed that drug binding produces a variety
      of structural changes in the motor, including in loop L5 and the neck linker.
      What is not clear from static crystallographic models, however, is the sequence
      of structural changes produced by drug binding. Furthermore, because
      crystallographic structures can be influenced by the packing forces in the
      crystal, it also remains unclear whether these drug-induced changes occur in
      solution, at physiologically active concentrations of monastrol or of other drugs
      that target this site. We have addressed these issues by using a series of
      spectroscopic probes to monitor the structural consequences of drug binding. Our
      results demonstrated that the crystallographic model of an Eg5-ADP-monastrol
      ternary complex is consistent with several solution-based spectroscopic probes.
      Furthermore, the kinetics of these spectroscopic signal changes allowed us to
      determine the temporal sequence of drug-induced structural transitions. These
      results suggested that L5 may be an element in the pathway that links the state
      of the nucleotide-binding site to the neck linker in kinesin motors.

PMID- 16434398
TI  - High resolution crystal structures and molecular dynamics studies reveal
      substrate binding in the porin Omp32.
AB  - The porin Omp32 is the major outer membrane protein of the bacterium Delftia
      acidovorans. The crystal structures of the strongly anion-selective porin alone
      and in complex with the substrate malate were solved at 1.5 and 1.45 A
      resolution, respectively, and revealed a malate-binding motif adjacent to the
      channel constriction zone. Binding is mediated by interaction with a cluster of
      two arginine residues and two threonines. This binding site is specific for Omp32
      and reflects the physiological adaptation of the organism to organic acids.
      Structural studies are combined with a 7-ns unbiased molecular dynamics
      simulation of the trimeric channel in a model membrane. Molecular dynamics
      trajectories show how malate ions are efficiently captured from the surrounding
      bulk solution by the electrostatic potential of the channel, translocated to the
      binding site region, and immobilized in the constriction zone. In accordance with
      these results, conductance measurements with Omp32 inserted in planar lipid
      membranes revealed binding of malate. The anion-selective channel Omp32 is the
      first reported example of a porin with a 16-stranded beta-barrel and proven
      substrate specificity. This finding suggests a new view on the correlation of
      porin structure with substrate binding in specific channels.

PMID- 16434399
TI  - Dynamic association between the catalytic and lectin domains of human UDP
      GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-2.
AB  - The family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases
      (ppGalNAcTs) is unique among glycosyltransferases, containing both catalytic and
      lectin domains that we have previously shown to be closely associated. Here we
      describe the x-ray crystal structures of human ppGalNAcT-2 (hT2) bound to the
      product UDP at 2.75 A resolution and to UDP and an acceptor peptide substrate EA2
      (PTTDSTTPAPTTK) at 1.64 A resolution. The conformations of both UDP and residues
      Arg362-Ser372 vary greatly between the two structures. In the hT2-UDP-EA2
      complex, residues Arg362-Ser373 comprise a loop that forms a lid over UDP,
      sealing it in the active site, whereas in the hT2-UDP complex this loop is folded
      back, exposing UDP to bulk solvent. EA2 binds in a shallow groove with threonine
      7 positioned consistent with in vitro data showing it to be the preferred site of
      glycosylation. The relative orientations of the hT2 catalytic and lectin domains
      differ dramatically from that of murine ppGalNAcT-1 and also vary considerably
      between the two hT2 complexes. Indeed, in the hT2-UDP-EA2 complex essentially no
      contact is made between the catalytic and lectin domains except for the peptide
      bridge between them. Thus, the hT2 structures reveal an unexpected flexibility
      between the catalytic and lectin domains and suggest a new mechanism used by hT2
      to capture glycosylated substrates. Kinetic analysis of hT2 lacking the lectin
      domain confirmed the importance of this domain in acting on glycopeptide but not
      peptide substrates. The structure of the hT2-UDP-EA2 complex also resolves long
      standing questions regarding ppGalNAcT acceptor substrate specificity.

PMID- 16434400
TI  - Low conductance gap junctions mediate specific electrical coupling in body-wall
      muscle cells of Caenorhabditis elegans.
AB  - Invertebrate innexins and their mammalian homologues, the pannexins, are gap
      junction proteins. Although a large number of such proteins have been identified,
      few of the gap junctions that they form have been characterized to provide
      combined information of biophysical properties, coupling pattern, and molecular
      compositions. We adapted the dual whole cell voltage clamp technique to in situ
      analysis of electrical coupling in Caenorhabditis elegans body-wall muscle. We
      found that body-wall muscle cells were electrically coupled in a highly organized
      and specific pattern. The coupling was characterized by small (350 pS or less)
      junctional conductance (G(j)), which showed a bell-shaped relationship with
      junctional potential (V(j)) but was independent of membrane potential (V(m)).
      Injection of currents comparable to the junctional current (I(j)) into body-wall
      muscle cells caused significant depolarization, suggesting important functional
      relevance. The innexin UNC-9 appeared to be a key component of the gap junctions.
      Both Myc- and green fluorescent protein-tagged UNC-9 was localized to muscle
      intercellular junctions. G(j) was greatly inhibited in unc-9(fc16), a putative
      null mutant. Specific inhibition of UNC-9 function in muscle cells reduced
      locomotion velocity. Despite UNC-9 expression in both motor neurons and body-wall
      muscle cells, analyses of miniature and evoked postsynaptic currents in the unc-9
      mutant showed normal neuromuscular transmission. These analyses provide a
      relatively detailed description of innexin-based gap junctions in a native tissue
      and suggest that innexin-based small conductance gap junctions can play an
      important role in processes such as locomotion.

PMID- 16434401
TI  - 9-O-acetylation of exogenously added ganglioside GD3. The GD3 molecule induces
      its own O-acetylation machinery.
AB  - Sialic acids are sometimes 9-O-acetylated in a developmentally regulated and cell
      type-specific manner. Cells naturally expressing the disialoganglioside GD3 often
      O-acetylate the terminal sialic acid residue, giving 9-O-acetyl-GD3 (9AcGD3), a
      marker of neural differentiation and malignant transformation. We also reported
      that Chinese hamster ovary cells transfected with GD3 synthase can spontaneously
      O-acetylate some of the newly synthesized GD3. It is unclear whether such
      phenomena result from induction of the 9-O-acetylation machinery and whether
      induction is caused by the GD3 synthase protein or by the GD3 molecule itself. We
      now show that exogenously added GD3 rapidly incorporates into the plasma membrane
      of Chinese hamster ovary cells, and 9AcGD3 is detected after approximately 6 h.
      The incorporated GD3 and newly synthesized 9AcGD3 have a half-life of
      approximately 24 h. This phenomenon is also seen in other cell types, such as
      human diploid fibroblasts. Inhibitors of gene transcription, protein translation,
      or endoplasmic reticulum-to-Golgi transport each prevent induction of 9-O
      acetylation, without affecting GD3 incorporation. Inhibition of the initial
      clathrin-independent internalization of incorporated GD3 also blocks induction of
      9-O-acetylation. Thus, new synthesis of one or more components of the 9-O
      acetylation machinery is induced by incorporation and internalization of GD3.
      Prepriming with structurally related gangliosides fails to accelerate the onset
      of 9-O-acetylation of subsequently added GD3, indicating a requirement for
      specific recognition of GD3. To our knowledge, this is the first example wherein
      a newly expressed or exogenously introduced ganglioside induces de novo synthesis
      of an enzymatic machinery to modify itself, and the first evidence for a
      mechanism of induction of sialic acid O-acetylation.

PMID- 16434402
TI  - Gemin8 is a novel component of the survival motor neuron complex and functions in
      small nuclear ribonucleoprotein assembly.
AB  - The survival motor neuron (SMN) protein is the product of the spinal muscular
      atrophy disease gene. SMN and Gemin2-7 proteins form a large macromolecular
      complex that localizes in the cytoplasm as well as in the nucleoplasm and in
      nuclear Gems. The SMN complex interacts with several additional proteins and
      likely functions in multiple cellular pathways. In the cytoplasm, a subset of SMN
      complexes containing unrip and Sm proteins mediates the assembly of spliceosomal
      small nuclear ribonucleoproteins (snRNPs). Here, by mass spectrometry analysis of
      SMN complexes purified from HeLa cells, we identified a novel protein that is
      evolutionarily conserved in metazoans, and we named it Gemin8. Co
      immunoprecipitation and immunolocalization experiments demonstrated that Gemin8
      is associated with the SMN complex and is localized in the cytoplasm and in the
      nucleus, where it is highly concentrated in Gems. Gemin8 interacts directly with
      the Gemin6-Gemin7 heterodimer and, together with unrip, these proteins form a
      heteromeric subunit of the SMN complex. Gemin8 is also associated with Sm
      proteins, and Gemin8-containing SMN complexes are competent to carry out snRNP
      assembly. Importantly, RNA interference experiments indicate that Gemin8 knock
      down impairs snRNP assembly, and Gemin8 expression is down-regulated in cells
      with low levels of SMN. These results demonstrate that Gemin8 is a novel integral
      component of the SMN complex and extend the repertoire of cellular proteins
      involved in the pathway of snRNP biogenesis.

PMID- 16434403
TI  - Serial analysis of gene expression in mouse uterus at the implantation site.
AB  - Although oligonucleotide chips, cDNA microarrays, differential display reverse
      transcription-PCR, and other approaches have been used to screen implantation
      related molecules, the mechanism by which embryo implantation occurs is still
      unknown. The aim of this study was to profile the differential gene expression
      between interimplantation site and implantation site in mouse uterus on day 5 of
      pregnancy by serial analysis of gene expression (SAGE). In our two SAGE libraries
      of 11-bp tags, the total numbers of tags sequenced were 48,121 for the
      interimplantation site and 50,227 for the implantation site. There were 1,039
      tags specifically expressed at interimplantation site, and 1,252 tags
      specifically expressed at the implantation site. Based on the p value, there were
      195 tags significantly up-regulated at the interimplantation site and 261 tags
      significantly up-regulated at the implantation site, of which 100 genes were
      single matched at the interimplantation site and 127 genes were single matched at
      the implantation site, respectively. By reverse transcription-PCR, the tag ratio
      between the implantation site and interimplantation site was verified on 14
      significantly changed genes. Using in situ hybridization, 1810014L12Rik, Psmb5,
      Cd63, Npm1, Fads3, and Tagln2 were shown to be highly expressed at the
      implantation site compared with the interimplantation site. Compared with the
      interimplantation site, Ddx39 was strongly expressed in the subluminal stromal
      cells at the implantation site on day 5 of pregnancy. Ddx39 expression at the
      implantation site was specifically induced by active blastocysts. Additionally,
      Ddx39 expression was significantly up-regulated by estrogen in the ovariectomized
      mice. In our SAGE data, many implantation-related genes were identified in mouse
      uterus. Our data could be a valuable source for future study on embryo
      implantation.

PMID- 16434404
TI  - Beta ig-h3 interacts directly with biglycan and decorin, promotes collagen VI
      aggregation, and participates in ternary complexing with these macromolecules.
AB  - Recombinant human beta ig-h3 was found to bind 125I-labeled small leucine-rich
      proteoglycans (SLRPs), biglycan, and decorin, in co-immunoprecipitation
      experiments. In each instance the binding could be blocked by an excess of the
      unlabeled proteoglycan, confirming the specificity of the interaction. Scatchard
      analysis showed that biglycan bound beta ig-h3 more avidly than decorin with Kd
      values estimated as 5.88 x 10(-8) and 1.02 x 10(-7) M, respectively. In
      reciprocal blocking experiments both proteoglycans inhibited the others binding
      to beta ig-h3 indicating that they may share the same binding site or that the
      two binding sites are in close proximity on the beta ig-h3 molecule. Since beta
      ig-h3 and the SLRPs are known to be associated with the amino-terminal region of
      collagen VI in tissue microfibrils, the effects of including collagen VI in the
      incubations were investigated. Co-immunoprecipitation of 125I-labeled biglycan
      incubated with equimolar mixtures of beta ig-h3 and pepsin-collagen VI was
      increased 6-fold over beta ig-h3 alone and 3-fold over collagen VI alone. Similar
      increases were also observed for decorin. The findings indicate that beta ig-h3
      participates in a ternary complex with collagen VI and SLRPs. Static light
      scattering techniques were used to show that beta ig-h3 rapidly forms very high
      molecular weight complexes with both native and pepsin-collagen VI, either alone
      or with the SLRPs. Indeed beta ig-h3 was shown to form a complex with collagen VI
      and biglycan, which appeared to be much more extensive than that formed by beta
      ig-h3 with collagen VI and decorin or those formed between the collagen and beta
      ig-h3, biglycan, or decorin alone. Biglycan core protein was shown to inhibit the
      extent of complexing of beta ig-h3 with native and pepsin-collagen VI suggesting
      that the glycosaminoglycan side chains of the proteoglycan were important for the
      formation of the large ternary complexes. Further studies showed that the direct
      interaction between beta ig-h3 and biglycan and between biglycan and collagen VI
      were also important for the formation of these complexes. The globular domains of
      collagen VI also appeared to have an influence on the interaction of the three
      components. Overall the results indicate that beta ig-h3 can differentially
      modulate the aggregation of collagen VI with biglycan and decorin. Thus this
      interplay is likely to be important in tissues such as cornea where such
      complexes are considered to occur.

PMID- 16434405
TI  - A mutation linked with autism reveals a common mechanism of endoplasmic reticulum
      retention for the alpha,beta-hydrolase fold protein family.
AB  - A mutation linked to autistic spectrum disorders encodes an Arg to Cys
      replacement in the C-terminal portion of the extracellular domain of neuroligin
      3. The solvent-exposed Cys causes virtually complete retention of the protein in
      the endoplasmic reticulum when the protein is expressed in transfected cells. An
      identical Cys substitution was reported for butyrylcholinesterase through
      genotyping patients with post-succinylcholine apnea. Neuroligin,
      butyrylcholinesterase, and acetylcholinesterase are members of the alpha,beta
      hydrolase fold family of proteins sharing sequence similarity and common tertiary
      structures. Although these proteins have distinct oligomeric assemblies and
      cellular dispositions, homologous Arg residues in neuroligin-3 (Arg-451), in
      butyrylcholinesterase (Arg-386), and in acetylcholinesterase (Arg-395) are
      conserved in all studied mammalian species. To examine whether an homologous Arg
      to Cys mutation affects related proteins similarly despite their differing
      capacities to oligomerize, we inserted homologous mutations in the
      acetylcholinesterase and butyrylcholinesterase cDNAs. Using confocal fluorescence
      microscopy and analysis of oligosaccharide processing, we find that the
      homologous Arg to Cys mutation also results in endoplasmic reticulum retention of
      the two cholinesterases. Small quantities of mutated acetylcholinesterase
      exported from the cell retain activity but show a greater K(m), a much smaller
      k(cat), and altered substrate inhibition. The nascent proteins associate with
      chaperones during processing, but the mutation presumably restricts processing
      through the endoplasmic reticulum and Golgi apparatus, because of local protein
      misfolding and inability to oligomerize. The mutation may alter the capacity of
      these proteins to dissociate from their chaperone prior to oligomerization and
      processing for export.

PMID- 16434407
TI  - Heparan sulfate plays a central role in a dynamic in vitro model of protein
      losing enteropathy.
AB  - Protein-losing enteropathy (PLE), the loss of plasma proteins through the
      intestine, is a symptom in ostensibly unrelated diseases. Emerging commonalities
      indicate that genetic insufficiencies predispose for PLE and environmental
      insults, e.g. viral infections and inflammation, trigger PLE onset. The specific
      loss of heparan sulfate (HS) from the basolateral surface of intestinal
      epithelial cells only during episodes of PLE suggests a possible mechanistic
      link. In the first tissue culture model of PLE using a monolayer of intestinal
      epithelial HT29 cells, we proved that HS loss directly causes protein leakage and
      amplifies the effects of the proinflammatory cytokine tumor necrosis factor alpha
      (TNFalpha). Here, we extend our in vitro model to assess the individual and
      combined effects of HS loss, interferon gamma (IFNgamma), TNFalpha, and increased
      pressure, and find that HS plays a central role in the patho-mechanisms
      underlying PLE. Increased pressure, mimicking venous hypertension seen in post
      Fontan PLE patients, substantially increased protein leakage, but HS loss,
      IFNgamma, or TNFalpha alone had only minor effects. However, IFNgamma up
      regulated TNFR1 expression and amplified TNFalpha-induced protein leakage.
      IFNgamma and TNFalpha compromised the integrity of the HT29 monolayer and made it
      more susceptible to increased pressure. HS loss itself compromises the integrity
      of the monolayer, amplifying the effects of pressure, but also amplifies the
      effects of both cytokines. In the absence of HS a combination of increased
      pressure, IFNgamma, and TNFalpha caused maximum protein leakage. Soluble heparin
      fully compensated for HS loss, providing a reasonable explanation for patient
      favorable response to heparin therapy.

PMID- 16434406
TI  - Identification of morphine-6-glucuronide in chromaffin cell secretory granules.
AB  - We report for the first time that morphine-6-glucuronide, a highly analgesic
      morphine-derived molecule, is present in adrenal chromaffin granules and secreted
      from chromaffin cells upon stimulation. We also demonstrate that
      phosphatidylethanolamine-binding protein (alternatively named Raf-1 kinase
      inhibitor protein or RKIP) acts as an endogenous morphine-6-glucuronide-binding
      protein. An UDP-glucuronosyltransferase 2B-like enzyme, described to transform
      morphine into morphine-6-glucuronide, has been immunodetected in the chromaffin
      granule matrix, and morphine-6-glucuronide de novo synthesis has been
      characterized, demonstrating the possible involvement of intragranular UDP
      glucuronosyltransferase 2B-like enzyme in morphine-6-glucuronide metabolism. Once
      secreted into the circulation, morphine-6-glucuronide may mediate several
      systemic actions (e.g. on immune cells) based on its affinity for mu-opioid
      receptors. These activities could be facilitated by phosphatidylethanolamine
      binding protein (PEBP), acting as a molecular shield and preventing morphine-6
      glucuronide from rapid clearance. Taken together, our data represent an important
      observation on the role of morphine-6-glucuronide as a new endocrine factor.

PMID- 16434408
TI  - Ganoderma extract prevents albumin-induced oxidative damage and chemokines
      synthesis in cultured human proximal tubular epithelial cells.
AB  - BACKGROUND: Ganoderma lucidum (Ganoderma or lingzhi) is widely used as an
      alternative medicine remedy to promote health and longevity. Recent studies have
      indicated that components extracted from Ganoderma have a wide range of
      pharmacological actions including suppressing inflammation and scavenging free
      radicals. We recently reported that tubular secretion of interleukin-8 (IL-8)
      induced by albumin is important in the pathogenesis of tubulointerstitial injury
      in the proteinuric state. In this study, we explored the protective effect of
      Ganoderma extract (LZ) on albumin-induced kidney epithelial injury. METHODS:
      Growth arrested human proximal tubular epithelial cells (PTECs) were incubated
      with 0.625 to 10 mg/ml human serum albumin (HSA) for up to 72 h. HSA induced DNA
      damage and apoptosis in PTEC in a dose- and time-dependent manner. Co-incubation
      of PTEC with 4-64 microg/ml LZ significantly reduced the oxidative damage and
      cytotoxic effect of HSA in a dose-dependent manner (P<0.001). Increased release
      of IL-8 and soluble intercellular adhesion molecules-1 (sICAM-1) in PTEC induced
      by HSA was ameliorated by co-incubation with Ganoderma (16 microg/ml). To explore
      the components of LZ that exhibited most protective effect in HSA-induced PTEC
      damages, LZ was further separated into two sub-fractions, LZF1 (MW <30 kDa) and
      LZF2 (MW <3 kDa), by molecular sieving using millipore membrane. PTEC were
      incubated with 5 mg/ml HSA in the presence of different doses of LZF1, LZF2 or
      unfractionated LZ. RESULTS: There was no difference in the degree of protection
      from HSA-induced cytotoxicity or oxidative DNA damage between different fractions
      of LZ. However, low molecular weight LZ (<3 kDa) was most effective in reducing
      sICAM-1 released from HSA-activated PTEC whereas the high molecular weight LZ
      (unfractionated LZ) was more effective in diminishing IL-8 production.
      CONCLUSIONS: Our results suggest that Ganoderma significantly reduces oxidative
      damages and apoptosis in PTEC induced by HSA. The differential reduction of IL-8
      or sICAM-1 released from HSA-activated PTEC by different components of the LZ
      implicates that components of Ganoderma with different molecular weights could
      play different roles and operate different mechanisms in preventing HSA-induced
      PTEC damage.

PMID- 16434409
TI  - Association between BP and mortality in patients on chronic peritoneal dialysis.

PMID- 16434410
TI  - Oxidative modification of tropomyosin and myocardial dysfunction following
      coronary microembolization.
AB  - AIMS: We addressed a potential mechanism of myocardial dysfunction following
      coronary microembolization at the level of myofibrillar proteins. METHODS AND
      RESULTS: Anaesthetized pigs underwent intracoronary infusion of microspheres.
      After 6 h, the microembolized areas (MEA) had decreased systolic wall thickening
      to 38 +/- 7% of baseline and a 2.62 +/- 0.40-fold increase in the formation of
      disulphide cross-bridges (DCB) in tropomyosin relative to that in remote areas.
      The impairment in contractile function correlated inversely with DCB formation (r
      = -0.68; P = 0.015) and was associated with increased TNF-alpha content. DCB
      formation was reflected by increased tropomyosin immunoreactivity and abolished
      in vitro by dithiothreitol. Ascorbic acid prevented contractile dysfunction as
      well as increased DCB and TNF-alpha. In anaesthetized dogs, 8 h after
      intracoronary microspheres infusion, contractile function was reduced to 8+/-10%
      of baseline and DCB in MEA was 1.48+/-0.12 higher than that in remote areas. In
      conscious dogs, 6 days after intracoronary microspheres infusion, myocardial
      function had returned to baseline and DCB was no longer different between remote
      and MEA. Again contractile function correlated inversely with DCB formation (r = 
      0.83; P = 0.005). CONCLUSION: Myofibrillar protein oxidation may represent a
      mechanistic link between inflammation and contractile dysfunction following
      coronary microembolization.

PMID- 16434411
TI  - Coronary endothelial dysfunction is associated with erectile dysfunction and
      elevated asymmetric dimethylarginine in patients with early atherosclerosis.
AB  - AIMS: Coronary endothelial dysfunction (CED) precedes atherosclerosis and is
      associated with cardiovascular events. Both CED and erectile dysfunction (ED) are
      partly mediated by impairment in the nitric oxide pathway. ED is associated with
      established coronary atherosclerosis, but its relationship with early coronary
      atherosclerosis and CED is unknown. This study was designed to test the
      hypothesis that CED is associated with ED in men with early coronary
      atherosclerosis. Moreover, the role of the nitric oxide synthase inhibitor
      asymmetric dimethylarginine (ADMA) was investigated; ADMA is a novel endogenous
      competitive inhibitor of nitric oxide synthase and has been shown to be an
      independent marker for cardiovascular disease. METHODS AND RESULTS: Fifty-six men
      without obstructive coronary artery disease (CAD) who underwent coronary
      endothelial function testing were studied. ADMA levels were determined and all
      men were asked to complete the International Index of Erectile Function-5
      questionnaire to assess erectile function. Patients were divided according to the
      presence (n = 32) or absence (n = 24) of CED. Men with CED had significant
      impairment of erectile function (P = 0.008) and significantly higher ADMA levels
      (0.50 +/- 0.06 vs. 0.45 +/- 0.07 ng/mL, P = 0.017) compared with men with normal
      endothelial function. Erectile function positively correlated with coronary
      endothelial function. This correlation was independent of age, body mass index,
      high-density lipoprotein, C-reactive protein, homeostasis model assessment of
      insulin resistance index, and smoking status. CONCLUSION: CED is independently
      associated with ED and plasma ADMA concentration in men with early coronary
      atherosclerosis. This study further supports the role of the endothelium in
      systemic vascular diseases and the role of ADMA in the systemic manifestations of
      endothelial dysfunction.

PMID- 16434412
TI  - Osteopontin, coronary calcification, and cardiovascular events: future diagnostic
      and therapeutic targets for disease prevention?

PMID- 16434413
TI  - Functional significance of myofilament protein oxidation.

PMID- 16434414
TI  - Assessment of reversible myocardial dysfunction in chronic ischaemic heart
      disease: comparison of contrast-enhanced cardiovascular magnetic resonance and a
      combined positron emission tomography-single photon emission computed tomography
      imaging protocol.
AB  - AIMS: The aim of the study was to compare, in patients with chronic ischaemic
      cardiomyopathy, contrast-enhanced cardiovascular magnetic resonance (ce-CMR)
      imaging and a combined (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission
      tomography (PET) and (99m)Tc-sestamibi single-photon emission computed tomography
      (SPECT) protocols for the prediction of functional recovery after
      revascularization, as assessed by cine CMR. METHODS AND RESULTS: Twenty-nine
      patients with ischaemic cardiomyopathy (ejection fraction 32 +/- 10%) were
      investigated with ce-CMR and PET/SPECT. For the assessment of global and regional
      functions, cine CMR was performed at baseline and at 6 months follow-up. For ce
      CMR, the segmental extent of hyperenhancement (SEH) was quantitated, and for
      PET/SPECT, different viability categories were defined according to a validated
      quantitative protocol. Functional improvement was related to the SEH by ce-CMR,
      as well as to the viability categories by PET/SPECT. Sensitivity and specificity
      for the prediction of functional recovery at follow-up was 97 and 68% for ce-CMR
      and 87 and 76% for PET/SPECT. The positive predictive value was identical for
      both techniques (73%). However, ce-CMR achieved a higher negative predictive
      value (93 vs. 77%, respectively), indicating that ce-CMR may be superior to
      PET/SPECT for the identification of segments unlikely to recover function after
      revascularization. Both methods had a similar yield in the prediction of global
      functional improvement. CONCLUSION: ce-CMR is comparable with a PET/SPECT imaging
      protocol for the prediction of regional and global functional improvement after
      revascularization. However, ce-CMR may be superior to nuclear imaging for the
      identification of segments that are unlikely to recover function at follow-up.

PMID- 16434415
TI  - The fate of systemic blood pressure in patients after effectively stented
      coarctation.
AB  - AIMS: The current study was designed to assess midterm results of stent
      implantation into the aorta for native and recurrent coarctation (CoA) in
      children and young adults. METHODS AND RESULTS: Forty-three patients (native CoA,
      8; female, 12) were treated with stent implantation at a median age of 16.8 years
      (range 7.9-44.8 years). Only stents dilatable to an adult size aorta were
      implanted. All but two patients with functionally univentricular hearts had
      arterial hypertension. Exercise tests, 24-h blood pressure, clinical examination,
      echocardiography, and elective catheterization were used to assess follow-up. The
      narrowed segment was widened significantly from a median of 8 to 12.4 mm (P <
      0.0005). The peak-to-peak gradient between the ascending and the descending aorta
      was lowered significantly from a median of 22 mmHg to 1 mmHg (P < 0.0005). No
      major complications occurred. The systolic blood pressure at the right arm was
      lowered significantly (P < 0.0005) from 144 mmHg before stent implantation to 128
      mmHg at the last visit. At a median follow-up of 30 months (3-72 months), 68% of
      all patients were classified to be normotensive. CONCLUSION: Stent implantation
      for selected patients with recurrent and native CoA is safe and may effectively
      reduce the blood pressure gradient across the CoA site. We suggest using only
      stents dilatable to an adult size aorta. However, arterial hypertension persists
      in a significant number of the patients. Impaired elastic properties of the aorta
      may be the cause for this finding.

PMID- 16434416
TI  - Elevated levels of remnant lipoproteins are associated with plasma platelet
      microparticles in patients with type-2 diabetes mellitus without obstructive
      coronary artery disease.
AB  - AIMS: Platelets participate in the pathogenesis of arterial thrombosis and it has
      been demonstrated that enhanced platelet activation occurs in patients with
      diabetes mellitus (DM). Dyslipidaemia is a common feature of diabetes. We
      investigated the association between certain lipid fractions and plasma platelet
      derived microparticle (PMP) levels in patients with type-2 DM. METHODS AND
      RESULTS: We measured fasting serum levels of remnant-like lipoprotein particles
      cholesterol (RLP-cholesterol) and assessed in vivo platelet activation by
      quantifying the number of PMP in the plasma detected as CD42b-positive
      microparticles by flow cytometry in Japanese type-2 DM patients without
      obstructive coronary artery disease who were more slender when compared with
      Western diabetic patients. The levels of total cholesterol, triglycerides, RLP
      cholesterol, and plasma glucose were significantly higher in patients with type-2
      DM (n = 105) than in non-diabetic patients (n = 92). The plasma levels of PMP
      were elevated significantly in type-2 DM patients when compared with non-diabetic
      control subjects [7.41(5.39-10.50) x 10(6) vs. 3.44(2.43-4.41)x10(6), P < 0.001].
      We found that RLP-cholesterol levels were the best predictor of PMP in
      multivariable linear regression analyses (beta = 0.375, P < 0.001). Lipid
      lowering medication with bezafibrate successfully reduced levels of both RLP
      cholesterol and PMP in patients with type-2 DM (P < 0.05). CONCLUSIONS: RLP
      cholesterol and platelet microparticles are both elevated in type-2 DM patients
      when compared with controls. RLP-cholesterol is the primary and only predictor of
      platelet microparticles in the multivariable analysis, which include several
      standard atherosclerosis risk factors. This suggested that reducing elevated RLP
      cholesterol with lipid-lowering therapy may be an effective strategy to prevent
      thrombogenic vascular complications in type-2 DM.

PMID- 16434417
TI  - Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study
      in syringomyelia.
AB  - The pathophysiology of central pain syndromes is still poorly understood and
      their treatment remains a major challenge. It has long been suggested that
      lesions of the spinothalamic pathways are necessary for developing these pain
      syndromes. The recently proposed thermosensory disinhibition theory suggests that
      reduction of the inhibition of thermal sensory afferents that affect nociceptive
      systems may play a major pathophysiological role. Syringomyelia, which is
      frequently associated with central neuropathic pain, is characterized by a
      selective or preferential lesion of the spinothalamic tract resulting in
      thermosensory deficits of various extents and magnitudes. Thus, syringomyelia
      represents a unique 'pathological model' particularly suited to investigating the
      relationship between spinothalamic tract dysfunction, thermosensory deficits and
      pain. Here, we systematically compared the sensory loss (thermal and mechanical),
      using quantitative sensory testing, between 46 consecutive syringomyelia patients
      with or without neuropathic pain. We then further investigated the mechanisms of
      evoked pains in these patients, using functional MRI (fMRI) in a subgroup of
      patients with cold or brush-evoked allodynia, compared with patients without pain
      and healthy volunteers. We found no significant difference in the magnitude or
      extent of sensory deficits between patients with or without neuropathic pain,
      suggesting that lesions of the spinothalamic pathways are not sufficient for
      developing central pain. However, a different pattern of sensory deficits was
      observed between patients with spontaneous pain only (n = 11) and patients with
      both spontaneous pain and allodynia (n = 20), suggesting that the mechanisms of
      central pain are not univocal. In patients with spontaneous pain only, the
      thermal sensory loss was significantly more asymmetrical and there was a direct
      relationship between the extent of thermosensory deficits (i.e. deafferentation)
      and the intensity of burning pain. In contrast, patients with allodynia had
      reduced thermal deficits, in terms of both magnitude and extent. In addition, the
      sensory deficits were different between patients with cold or tactile allodynia,
      suggesting distinct pathophysiological mechanisms related to the sub-modalities
      of allodynia. Our fMRI study further confirmed this, showing that different sub
      types of allodynia were associated with distinct patterns of brain activity,
      which do not necessarily correspond to the 'pain matrix' involved in acute
      physiological pain. The prefrontal cortex was the only area consistently
      activated by pathological evoked pains, suggesting that alteration of high-level
      pain modulatory mechanisms might play a major role in allodynia due to central
      lesion.

PMID- 16434418
TI  - Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory
      neuropathy maps to chromosome 2q37.3.
AB  - The hereditary spastic paraplegias (HSPs) are a clinically and genetically
      heterogeneous group of neurodegenerative diseases characterized by progressive
      spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped
      so far, and 11 responsible genes have been identified. Clinically, one
      distinguishes between pure and complex HSP forms which are variably associated
      with numerous combinations of neurological and extra-neurological signs. Less is
      known about autosomal recessive forms (ARHSP) since the mapped loci have been
      identified often in single families and account for only a small percentage of
      patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a
      consanguineous family with seven unaffected and four affected members of Algerian
      origin living in Eastern France with a significant multipoint lod score of 3.8.
      Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the
      Czech Republic (n = 1) were not linked to the newly identified locus thus
      demonstrating further genetic heterogeneity. The phenotype of the linked family
      consists of spastic paraparesis and peripheral neuropathy associated with slight
      cerebellar signs confirmed by cerebellar atrophy on one CT scan.

PMID- 16434421
TI  - Thinking about the cerebellum.

PMID- 16434422
TI  - Cognition, emotion and the cerebellum.

PMID- 16434423
TI  - Government-NGO collaboration: the case of tuberculosis control in Bangladesh.
AB  - This study analyzes the basic concepts and key issues of existing collaboration
      between government and non-governmental organizations (NGOs) in health care,
      using as an example the implementation of the DOTS (formerly an abbreviation for
      directly observed treatment, short course) strategy for tuberculosis (TB) control
      in Bangladesh. It also examines efforts by the Government of Bangladesh to
      improve health services delivery, especially for the poor, through collaboration
      with NGOs. Data were collected in 2001 and 2002 as a part of the process of
      developing a public-private partnership model for TB care in Bangladesh. Analyses
      of existing collaboration models in TB control strongly suggest that the
      government and NGO sectors can be complementary in controlling TB. We found an
      increasing trend of government collaborating with NGOs in implementing TB control
      programmes. The study indicates that government-NGO collaboration is an effective
      way of improving access to and quality of TB and other health care services.

PMID- 16434424
TI  - Imbalances in the health labour force: an assessment using data from three
      national health facility surveys.
AB  - Accurate knowledge of the characteristics of the health labour force that can
      affect health care production is of critical importance to health planners and
      policymakers. This study uses health facility survey data to examine
      characteristics of the primary health care labour force in Nicaragua, Tanzania
      and Bangladesh. The characteristics examined are those that are likely to affect
      service provision, including urban/rural distribution, demographic
      characteristics, and experience and in-service training, for three types of
      providers (physicians, nurses and auxiliary nurses). The profiles suggest a
      pattern of urban/rural imbalances in Nicaragua and Tanzania. The Bangladesh
      facility survey did not include hospitals, thereby making concrete conclusions on
      the supply and distribution of providers difficult to make. Multivariate logistic
      regressions are used to assess the relationship between the urban/rural placement
      of providers by health need, population demand and facility characteristics.
      Health need, as measured by child mortality rates, does not have a significant
      association with the placement of providers in either country, unlike population
      size and annual growth rates. The mean number of years providers have worked at a
      facility is significantly associated with a decreased likelihood of rural
      placement for the three types of providers in Nicaragua. The mean age and
      percentage of female providers at each facility has a negative association with
      the placement of rural providers in Tanzania. The use of health facility data to
      profile the health care labour force is also discussed.

PMID- 16434425
TI  - Insulin-like growth factor I improves intestinal barrier function in cirrhotic
      rats.
AB  - BACKGROUND AND AIMS: In liver cirrhosis, disruption of the intestinal barrier
      facilitates bacterial translocation and spontaneous bacterial peritonitis.
      Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by
      hepatocytes that displays hepatoprotective activities and trophic effects on the
      intestine. The aim of this study was to investigate the effect of IGF-I on
      intestinal barrier function in cirrhotic rats. METHODS: In rats with carbon
      tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on:
      (a) portal pressure; (b) intestinal histology and permeability to endotoxin and
      bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour
      necrosis factor alpha (TNF-alpha), two factors that influence in a positive and
      negative manner, respectively, the integrity of the intestinal barrier; (d)
      intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and
      (e) transepithelial electrical resistance (TER) of polarised monolayers of rat
      small intestine epithelial cells. RESULTS: IGF-I therapy reduced liver collagen
      expression and portal pressure in cirrhotic rats, induced improvement in
      intestinal histology, and caused a reduction in bacterial translocation and
      endotoxaemia. These changes were associated with diminished TNF-alpha expression
      and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability
      in BDL rats and enhanced barrier function of the monolayers of epithelial
      intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was
      reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2
      in LPS treated enterocytes. CONCLUSIONS: IGF-I enhances intestinal barrier
      function and reduces endotoxaemia and bacterial translocation in cirrhotic rats.
      IGF-I therapy might be useful in the prevention of spontaneous bacterial
      peritonitis in liver cirrhosis.

PMID- 16434426
TI  - Higher clearance of hepatitis C virus infection in females compared with males.
AB  - BACKGROUND AND AIMS: According to the literature, 14-46% of subjects clear
      hepatitis C virus (HCV) from blood after infection. Controversy exists about sex
      differences in HCV clearance rates. PATIENTS AND METHODS: We compared HCV
      clearance in males and females using data from a large population based study on
      HCV infection in Egypt. Definitions used in the paper were: cleared HCV infection
      (positive HCV antibody and negative HCV RNA test results) and chronic HCV
      infection (positive HCV antibody and positive HCV RNA test results). The study
      sample included 4720 village residents aged 18-65 years recruited through home
      based visits (n = 2425) or voluntary screening (n = 2295). RESULTS: Overall, HCV
      antibody prevalence was 910/4720 (19.3% (95% confidence interval 18.2-20.4)). Of
      those with HCV antibodies (n = 910), 61.5% had chronic HCV infection. Compared
      with males, females were more likely to have cleared the virus (44.6% v 33.7%,
      respectively; p = 0.001). Control for age, schistosomiasis history, iatrogenic
      exposures, and sexual exposure to HCV did not alter the positive association
      between female sex and viral clearance. CONCLUSION: This study provides strong
      evidence in favour of a higher HCV clearance rate in females compared with males.

PMID- 16434429
TI  - Health consequences of the first Persian Gulf War on French troops.
AB  - Since 1993, many studies on the health of Persian Gulf War Veterans (PGWV) have
      been undertaken. These studies have concluded that there has been an increased
      mortality due to external causes, no excess of recognized diseases, and no effect
      on PGWV children. When compared with the non-deployed, PGWV have reported a
      higher frequency of infertility as well as different symptoms, but a specific
      Gulf War syndrome was not identified. In October 2000, the French government
      asked an independent working group to analyse the scientific literature on PGWV
      health. The group concluded that an exhaustive study of French PGWV was to be
      undertaken. The objectives of this study were to describe the exposures of PGWV
      in the operations theatre, to report on the symptoms and diseases that occurred
      in PGWV and their children during and after the military campaign, and to explore
      the possibility of a Gulf War syndrome. This exhaustive cross-sectional study,
      which included all civilians and troops who served in the Gulf from August 1990
      to July 1991, began in January 2002. Data were collected by postal self
      administered questionnaires. A standardized clinical evaluation was performed by
      27 clinics of occupational diseases and nine military hospitals. Symptoms and
      diseases which appeared after the campaign are described. To date, among 20,261
      PGWV, 5,666 participated in the study (28%). The most frequent symptoms described
      since the return from the Gulf were headaches (83%), neurological or
      psychological symptoms, and back pain. Apart from well-known symptoms
      associations (respiratory, neurocognitive, psychological and musculo-skeletal
      syndromes), no other cluster was highlighted by our analysis.

PMID- 16434431
TI  - What is the probability of successive cases of Legionnaires' disease occurring in
      European hotels?
AB  - BACKGROUND: Public health officials will normally take action at accommodation
      sites following an association with a cluster of cases of Legionnaires' disease.
      This paper seeks to determine the likelihood of such a cluster occurring at a
      site once it has been associated with a single case of the disease, and therefore
      whether more should be done at sites following individual cases. METHODS:
      Information for UK residents reported to the EWGLINET system between 1993 and
      2000 was included in a dataset. The size and country of hotel visited by the
      cases were divided into six country groups (France, Italy, Spain, Turkey, other
      Europe and other World), and eight size groups (<20 rooms, 20-49, 50-99, 100-199,
      200-299, 300-399, 400-499, 500+). The data were investigated using Cox
      proportional hazards regression to model the probability of at least one further
      case following the first. RESULTS: The dataset comprised 793 cases that had
      stayed at 605 sites in 51 countries between 1993 and the end of 2000. This
      included 605 cases that were the first case associated with a site, and 188
      subsequent cases. Following the first case, 16.6% of sites were associated with
      at least one subsequent case during the period under study. The probability of a
      subsequent case occurring within 6 months of the first varied by country and size
      group, with some combinations returning a probability >30%; the probability of a
      subsequent case occurring within 2 years of the first reached over 50% in some
      instances. CONCLUSIONS: There may be support for early intervention at some
      accommodation sites following a first case of Legionnaires' disease, in specific
      country and size groups.

PMID- 16434428
TI  - Meal induced rectosigmoid tone modification: a low caloric meal accurately
      separates functional and organic gastrointestinal disease patients.
AB  - BACKGROUND AND AIMS: Diagnosis of irritable bowel syndrome (IBS) is based on
      arbitrary criteria due to the lack of an accurate diagnostic test. The aim of
      this study was to evaluate whether rectosigmoid tone modification after a meal
      represents an accurate diagnostic approach. METHODS: In a secondary care setting,
      32 constipation predominant and 24 diarrhoea predominant IBS patients, 10
      functional diarrhoea and 10 functional constipation patients, 29 organic
      gastrointestinal disease patients, and 10 healthy volunteers underwent a rectal
      barostat test to measure fasting and postprandial rectosigmoid tone. Rectosigmoid
      response was assessed following three meals containing different amounts of
      calories: 200 kcal, 400 kcal and 1000 kcal. RESULTS: After 200 kcal, healthy
      volunteers and patients with organic diseases showed a reduction in rectosigmoid
      volume of at least 28% of fasting volume, indicating a meal induced increase in
      muscle tone. In contrast, patients with diarrhoea predominant IBS showed dilation
      of the rectosigmoid colon, indicative of reduced tone, and patients with
      constipation predominant IBS showed a mild volume reduction or no modification.
      Functional diarrhoea and constipation patients showed rectosigmoid tone
      modification resembling that of the corresponding IBS subtype. A 400 kcal meal
      normalised rectosigmoid tone in more than half of the constipation predominant
      IBS patients but none of the diarrhoea predominant IBS patients. In contrast, a
      1000 kcal meal normalised tone response in all IBS patients. Sensitivity of the
      test was 100%, specificity 93%, positive predictive value 96%, and negative
      predictive value 100%. CONCLUSION: A postprandial reduction in rectosigmoid tone
      of at least 28% of fasting value after a low caloric meal accurately separates
      organic and functional gastrointestinal disease patients. This parameter may
      therefore be used in the positive diagnosis of IBS.

PMID- 16434427
TI  - Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics
      in patients with early cirrhosis: a randomised controlled trial.
AB  - BACKGROUND AND AIMS: Increased endothelin (ET)-1 activity may contribute to the
      complications of cirrhosis and portal hypertension. The aim of this study was to
      assess the systemic and portal haemodynamic effects of selective ET-A and ET-B
      receptor antagonism in patients with cirrhosis. METHODS: Sixteen patients with
      cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3))
      underwent 24 studies with infusions of: (A) selective ET-A antagonist, BQ-123 (n
      = 8), at 1000 and 3000 nmol/min; (B) selective ET-B antagonist, BQ-788 (n = 8),
      at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind
      randomised manner. Haemodynamic measurements were performed through pulmonary
      artery, hepatic venous, and femoral artery catheters. RESULTS: Baseline patient
      characteristics were well matched. Compared with placebo, BQ-123 decreased mean
      arterial pressure (MAP -15 (11) mm Hg (-18%); p<0.02) and pulmonary vascular
      resistance index (PVRI -81 (54) dyn x s x m2/cm5 (-64%); p<0.05), with no effect
      on hepatic venous pressure gradient (HVPG), cardiac index (CI), or systemic
      vascular resistance index (SVRI). Compared with placebo, BQ-788 increased MAP
      (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn x s x m2/cm5 (+50%);
      p<0.05), reduced CI (-1.0 (0.4) l/min/m2 (-29%); p = 0.05) with no effect on HVPG
      or PVRI. CONCLUSIONS: ET-1 contributes to maintenance of systemic and pulmonary
      haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In
      this group of patients, the use of selective ET-A and ET-B antagonists for the
      management of variceal haemorrhage is likely to be limited.

PMID- 16434433
TI  - Maternal smoking during pregnancy and offspring IQ.

PMID- 16434434
TI  - An alloplasmic male-sterile line of Brassica oleracea harboring the mitochondria
      from Diplotaxis muralis expresses a novel chimeric open reading frame, orf72.
AB  - Nuclear so-called fertility-restorer genes reverse the pollen sterility of
      cytoplasmic male-sterile (CMS) plants caused by disturbed mitochondrial-nuclear
      interactions. We identified a CMS-associated chimeric mitochondrial gene in an
      alloplasmic CMS line of Brassica oleracea in the 'mur' system. This novel
      chimeric gene, orf72, was found in the mitochondrial genome of donor cytoplasm.
      It was located downstream of normal rps7 and contained part of atp9 (atp9-b). It
      was expressed specifically on the nuclear background of CMS B. oleracea,
      partially suppressed in the fertility-restored line and entirely suppressed in
      the cytoplasmic donor.

PMID- 16434435
TI  - An important pool of sucrose linked to starch biosynthesis is taken up by
      endocytosis in heterotrophic cells.
AB  - We have recently shown the occurrence of endocytic sucrose uptake in
      heterotrophic cells. Whether this mechanism is involved in the sucrose-starch
      conversion process was investigated by comparing the rates of starch accumulation
      in sycamore cells cultured in the presence or absence of the endocytic inhibitors
      wortmannin and 2-(4-morpholynyl-)-8-phenyl-4H-1 benzopyran-4-1 (LY294002). These
      analyses revealed a two-phase process involving an initial 120 min wortmannin-
      and LY294002-insensitive starch accumulation period, followed by a prolonged
      phase that was arrested by the endocytic inhibitors. Both wortmannin and LY294002
      led to a strong reduction of the intracellular levels of both sucrose and the
      starch precursor molecule, ADPglucose. No changes in maximum catalytic activities
      of enzymes closely linked to starch and sucrose metabolism occurred in cells
      cultured with endocytic inhibitors. In addition, starch accumulation was
      unaffected by endocytic inhibitors when cells were cultured with glucose. These
      results provide a first indication that an important pool of sucrose incorporated
      into the cell is taken up by endocytosis prior to its subsequent conversion into
      starch in heterotrophic cells. This conclusion was substantiated further by
      experiments showing that sucrose-starch conversion was strongly prevented by both
      wortmannin and LY294002 in both potato tuber discs and developing barley
      endosperms.

PMID- 16434436
TI  - Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. MHC
      Class I genes in the Tuatara (Sphenodon spp.): evolution of the MHC in an ancient
      reptilian order.
AB  - The major histocompatibility complex (MHC) is an extremely dynamic region of the
      genome, characterized by high polymorphism and frequent gene duplications and
      rearrangements. This has resulted in considerable differences in MHC organization
      and evolution among vertebrate lineages, particularly between birds and mammals.
      As nonavian reptiles are ancestral to both mammals and birds, they occupy an
      important phylogenetic position for understanding these differences. However,
      little is known about reptile MHC genes. To address this, we have characterized
      MHC class I sequences from the tuatara (Sphenodon spp.), the last survivor of an
      ancient order of reptiles, Sphenodontia. We isolated two different class I cDNA
      sequences, which share 93% sequence similarity with each other but are highly
      divergent from other vertebrate MHC genes. Southern blotting and polymerase chain
      reaction amplification of class I sequences from seven adult tuatara plus a
      family group indicate that these sequences represent at least two to three loci.
      Preliminary analysis of variation among individuals from an island population of
      tuatara indicates that these loci are highly polymorphic. Maximum likelihood
      analysis of reptile MHC class I sequences indicates that gene duplication has
      occurred within reptilian orders. However, the evolutionary relationships among
      sequences from different reptilian orders cannot be resolved, reflecting the
      antiquity of the major reptile lineages.

PMID- 16434437
TI  - Attitudes toward the use of quarantine in a public health emergency in four
      countries.
AB  - Countries worldwide face the threat of emerging infectious diseases. To
      understand the public's reaction to the use of widespread quarantine should such
      an outbreak occur, the Harvard School of Public Health, with the U.S. Centers for
      Disease Control and Prevention, undertook a survey of residents of Hong Kong,
      Taiwan, Singapore, and the United States. A sizable proportion of the public in
      each country opposed compulsory quarantine. Respondents were concerned about
      overcrowding, infection, and inability to communicate with family members while
      in quarantine. Officials will need specific plans to deal with the public's
      concerns about compulsory quarantine policies.

PMID- 16434438
TI  - VISSA: a program to visualize structural features from structure sequence
      alignment.
AB  - MOTIVATION: Multiple sequence alignment is an important tool to understand and
      analyze functions of homologous proteins. However, the logic of residue
      conservation/variation is usually apparent only in three-dimensional (3D) space,
      not on a primary sequence level. Thus, in a traditional multiple alignment it is
      often difficult to directly visualize and analyze key residues because they are
      masked by other residues along the alignment. Here we present an integrated
      multiple alignment and 3D structure visualization program that can (1) map and
      highlight residues from a 1D alignment onto a 3D structure and vice versa and (2)
      display only the alignment of preselected, key residues. This program, called
      Visualize Structure Sequence Alignment, also has many other built-in tools that
      can help analyze multiple sequence alignments. AVAILABILITY:
      http://bioinformatics.burnham.org/liwz/vissa CONTACT: liwz@burnham.org.

PMID- 16434439
TI  - Polynomial model approach for resynchronization analysis of cell-cycle gene
      expression data.
AB  - MOTIVATION: Identification of genes expressed in a cell-cycle-specific periodical
      manner is of great interest to understand cyclic systems which play a critical
      role in many biological processes. However, identification of cell-cycle
      regulated genes by raw microarray gene expression data directly is complicated by
      the factor of synchronization loss, thus remains a challenging problem.
      Decomposing the expression measurements and extracting synchronized expression
      will allow to better represent the single-cell behavior and improve the accuracy
      in identifying periodically expressed genes. RESULTS: In this paper, we propose a
      resynchronization-based algorithm for identifying cell-cycle-related genes. We
      introduce a synchronization loss model by modeling the gene expression
      measurements as a superposition of different cell populations growing at
      different rates. The underlying expression profile is then reconstructed through
      resynchronization and is further fitted to the measurements in order to identify
      periodically expressed genes. Results from both simulations and real microarray
      data show that the proposed scheme is promising for identifying cyclic genes and
      revealing underlying gene expression profiles. AVAILABILITY: Contact the authors.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at:
      http://dsplab.eng.umd.edu/~genomics/syn/

PMID- 16434440
TI  - Novel technique for preprocessing high dimensional time-course data from DNA
      microarray: mathematical model-based clustering.
AB  - MOTIVATION: Classifying genes into clusters depending on their expression
      profiles is one of the most important analysis techniques for microarray data.
      Because temporal gene expression profiles are indicative of the dynamic
      functional properties of genes, the application of clustering analysis to time
      course data allows the more precise division of genes into functional classes.
      Conventional clustering methods treat the sampling data at each time point as
      data obtained under different experimental conditions without considering the
      continuity of time-course data between time periods t and t+1. Here, we propose a
      method designated mathematical model-based clustering (MMBC). RESULTS: The
      proposed method, designated MMBC, was applied to artificial data and time-course
      data obtained using Saccharomyces cerevisiae. Our method is able to divide data
      into clusters more accurately and coherently than conventional clustering
      methods. Furthermore, MMBC is more tolerant to noise than conventional clustering
      methods. AVAILABILITY: Software is available upon request. CONTACT:
      taizo@brs.kyushu-u.ac.jp.

PMID- 16434441
TI  - CSS-Palm: palmitoylation site prediction with a clustering and scoring strategy
      (CSS).
AB  - Palmitoylation is an important post-translational lipid modification of proteins.
      Unlike prenylation and myristoylation, palmitoylation is a reversible covalent
      modification, allowing for dynamic regulation of multiple complex cellular
      systems. However, in vivo or in vitro identification of palmitoylation sites is
      usually time-consuming and labor-intensive. So in silico predictions could help
      to narrow down the possible palmitoylation sites, which can be used to guide
      further experimental design. Previous studies suggested that there is no unique
      canonical motif for palmitoylation sites, so we hypothesize that the bona fide
      pattern might be compromised by heterogeneity of multiple structural determinants
      with different features. Based on this hypothesis, we partition the known
      palmitoylation sites into three clusters and score the similarity between the
      query peptide and the training ones based on BLOSUM62 matrix. We have implemented
      a computer program for palmitoylation site prediction, Clustering and Scoring
      Strategy for Palmitoylation Sites Prediction (CSS-Palm) system, and found that
      the program's prediction performance is encouraging with highly positive Jack
      Knife validation results (sensitivity 82.16% and specificity 83.17% for cut-off
      score 2.6). Our analyses indicate that CSS-Palm could provide a powerful and
      effective tool to studies of palmitoylation sites. AVAILABILITY: CSS-Palm is
      implemented in PHP/PERL+MySQL and can be freely accessed at
      http://bioinformatics.lcd-ustc.org/css_palm/ CONTACT: yaoxb@ustc.edu.cn;
      xuyn@bmb.uga.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bionformatics online.

PMID- 16434442
TI  - Discontinuous epitope prediction based on mimotope analysis.
AB  - MOTIVATION: Phage display is a widespread technique used to obtain peptide
      mimotopes selected by binding to a given monoclonal antibody in a similar way as
      the native epitope. However, the localization of the interaction site mimicked by
      the mimotopes on the surface of the antigen is not always a straightforward task.
      MIMOP is a computational tool developed with the aim of helping experimentalists
      to analyze a set of mimotope sequences and guide them in the identification of
      the mimicked region. RESULTS: To predict potential epitopic regions, MIMOP
      integrates two different approaches combining two- and three-dimensional
      analyses: MimAlign starts from degenerated alignment analyses, and MimCons is
      based on consensus identification. The relevance and usefulness of the tool are
      illustrated by four use cases corresponding to real-life situations.

PMID- 16434443
TI  - Incorporating gene functions as priors in model-based clustering of microarray
      gene expression data.
AB  - MOTIVATION: Cluster analysis of gene expression profiles has been widely applied
      to clustering genes for gene function discovery. Many approaches have been
      proposed. The rationale is that the genes with the same biological function or
      involved in the same biological process are more likely to co-express, hence they
      are more likely to form a cluster with similar gene expression patterns. However,
      most existing methods, including model-based clustering, ignore known gene
      functions in clustering. RESULTS: To take advantage of accumulating gene
      functional annotations, we propose incorporating known gene functions as prior
      probabilities in model-based clustering. In contrast to a global mixture model
      applicable to all the genes in the standard model-based clustering, we use a
      stratified mixture model: one stratum corresponds to the genes of unknown
      function while each of the other ones corresponding to the genes sharing the same
      biological function or pathway; the genes from the same stratum are assumed to
      have the same prior probability of coming from a cluster while those from
      different strata are allowed to have different prior probabilities of coming from
      the same cluster. We derive a simple EM algorithm that can be used to fit the
      stratified model. A simulation study and an application to gene function
      prediction demonstrate the advantage of our proposal over the standard method.
      CONTACT: weip@biostat.umn.edu

PMID- 16434445
TI  - Computation of recurrent minimal genomic alterations from array-CGH data.
AB  - MOTIVATION: The identification of recurrent genomic alterations can provide
      insight into the initiation and progression of genetic diseases, such as cancer.
      Array-CGH can identify chromosomal regions that have been gained or lost, with a
      resolution of approximately 1 mb, for the cutting-edge techniques. The extraction
      of discrete profiles from raw array-CGH data has been studied extensively, but
      subsequent steps in the analysis require flexible, efficient algorithms,
      particularly if the number of available profiles exceeds a few tens or the number
      of array probes exceeds a few thousands. RESULTS: We propose two algorithms for
      computing minimal and minimal constrained regions of gain and loss from
      discretized CGH profiles. The second of these algorithms can handle additional
      constraints describing relevant regions of copy number change. We have validated
      these algorithms on two public array-CGH datasets. AVAILABILITY: From the
      authors, upon request. CONTACT: celine@lri.fr SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 16434444
TI  - COCO-CL: hierarchical clustering of homology relations based on evolutionary
      correlations.
AB  - MOTIVATION: Determining orthology relations among genes across multiple genomes
      is an important problem in the post-genomic era. Identifying orthologous genes
      can not only help predict functional annotations for newly sequenced or poorly
      characterized genomes, but can also help predict new protein-protein
      interactions. Unfortunately, determining orthology relation through computational
      methods is not straightforward due to the presence of paralogs. Traditional
      approaches have relied on pairwise sequence comparisons to construct graphs,
      which were then partitioned into putative clusters of orthologous groups. These
      methods do not attempt to preserve the non-transitivity and hierarchic nature of
      the orthology relation. RESULTS: We propose a new method, COCO-CL, for
      hierarchical clustering of homology relations and identification of orthologous
      groups of genes. Unlike previous approaches, which are based on pairwise sequence
      comparisons, our method explores the correlation of evolutionary histories of
      individual genes in a more global context. COCO-CL can be used as a semi
      independent method to delineate the orthology/paralogy relation for a refined set
      of homologous proteins obtained using a less-conservative clustering approach, or
      as a refiner that removes putative out-paralogs from clusters computed using a
      more inclusive approach. We analyze our clustering results manually, with support
      from literature and functional annotations. Since our orthology determination
      procedure does not employ a species tree to infer duplication events, it can be
      used in situations when the species tree is unknown or uncertain. CONTACT:
      jothi@mail.nih.gov, przytyck@mail.nih.gov SUPPLEMENTARY INFORMATION:
      Supplementary materials are available at Bioinformatics online.

PMID- 16434446
TI  - ProteomeCommons.org JAF: reference information and tools for proteomics.
AB  - SUMMARY: Analysis of proteomics data, specifically mass spectrometry data,
      commonly relies on libraries of known information such as atomic masses, known
      stable isotopes, atomic compositions of amino acids, observed modifications of
      known amino acids and ion masses that directly correspond to known amino acid
      sequences. The Java Analysis Framework (JAF) for proteomics provides a freely
      usable, open-source library of Java code that abstracts all of the aforementioned
      data, enabling more rapid development of proteomics tools. The JAF also includes
      several user tools that can be run directly from a web browser. AVAILABILITY: The
      current version and an archive of all older versions of the Java Analysis
      Framework for Proteomics is freely available, including complete source-code, at
      http://www.proteomecommons.org/current/511/.

PMID- 16434448
TI  - The repair of gamma-radiation-induced DNA damage is inhibited by microcystin-LR,
      the PP1 and PP2A phosphatase inhibitor.
AB  - The genotoxic activity of microcystin-LR (MC-LR) is a matter of debate. MC-LR is
      known to be a phosphatase inhibitor and it may be expected that it is involved in
      the regulation of the activity of DNA-dependent protein kinase (DNA-PK), the key
      enzyme involved in the repair of radiation-induced DNA damage. We studied the
      effect of MC-LR on the repair capacity of radiation-induced DNA damage in human
      lymphocytes and human glioblastoma cell lines MO59J and MO59K. A dose of 0.5
      microg/ml of MC-LR was chosen because it induced very little early apoptosis
      which gives no false positive results in the comet assay. Human lymphocytes in G0
      phase of the cell cycle were pre-treated with MC-LR for 3 h and irradiated with 2
      Gy of gamma radiation. The kinetics of DNA repair was assessed by the comet
      assay. In addition the frequencies of chromosomal aberrations were analysed. The
      pre-treatment with MC-LR inhibited the repair of radiation-induced damage and
      lead to enhanced frequencies of chromosomal aberrations including dicentric
      chromosomes. The results of a split-dose experiment, where cells were exposed to
      two 1.5 Gy doses of radiation separated by 3 h with or without MC-LR, confirmed
      that the toxin increased the frequency of dicentric chromosomes. We also
      determined the effect of MC-LR and ionizing radiation on the frequency of gamma
      H2AX foci. The pre-treatment with MC-LR resulted in reduced numbers of gamma-H2AX
      foci in irradiated cells. In order to elucidate the impact of MC-LR on DNA-PK we
      examined the kinetics of DNA repair in human glioblastoma MO59J and MO59K cells.
      Both cell lines were exposed to 10 Gy of X-rays and DNA repair was analysed by
      the comet assay. A strong inhibitory effect was observed in the MO59K but not in
      the MO59J cells. These results indicate that DNA-PK might be involved in DNA
      repair inhibition by MC-LR.

PMID- 16434449
TI  - Cadmium-induced genotoxicity, cytotoxicity and lipid peroxidation in Allium
      sativum and Vicia faba.
AB  - Cadmium (Cd) is one of the most toxic environmental pollutants affecting
      cytogenetically the various organisms. The cytogenetic damage in root tip cells
      exposed to cadmium nitrate (CdNO3) solutions at four different concentrations (1,
      10, 100 and 200 microM) was evaluated with biological tests based on micronucleus
      (MN) assay in two plant species, Allium sativum and Vicia faba. Additionally to
      the cytogenetic analysis, lipid peroxidation analyses were performed in both
      A.sativum and V.faba roots. Cd enhanced the MN frequency in both A.sativum and
      V.faba root tip cells, but no dose-dependent. Induction of MN is not depending on
      CdNO3 concentrations. Besides, high concentrations of Cd decreased the mitotic
      index and caused the delay in mitosis stages in both plants, mainly in V.faba. On
      the other hand, lipid peroxidation was significantly enhanced with external Cd in
      V.faba. The results clearly indicate that high concentrations of cadmium induce
      the lipid peroxidation resulting in oxidative stress that may contribute to the
      genotoxicity and cytotoxicity of Cd ions.

PMID- 16434450
TI  - Increased frequencies of both chromosome abnormalities and SCEs in two sheep
      flocks exposed to high dioxin levels during pasturage.
AB  - During the past four years several livestock farms (sheep, cattle and river
      buffalo) in the provinces of Naples and Caserta (southern Italy) have been unable
      to sell their milk and other dairy products due to the levels of dioxins (17
      different types) present in the milk mass exceeding the value permitted [3 pg/g
      of fat, as human WHO 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin)
      equivalent]. While some farms, especially those showing relatively low levels of
      dioxins, have managed to reduce the dioxins in the milk below the permitted
      threshold by changing the diet, many, especially sheep farms, have failed to do
      so. Indeed, about 12,000 head of cattle, river buffaloes and sheep have so far
      been culled. In the present study, 34 and 42 sheep from two herds raised in the
      province of Naples (Acerra municipality) and where high levels of dioxins (50.65
      and 39.51 pg/g of fat, respectively) were found in the milk mass, were
      cytogenetically investigated and compared with 20 sheep (control) raised 80 km
      away from the exposed area. Increases of both chromosome abnormalities (gap,
      chromosome and chromatid breaks) (17 and 8 times higher in the two exposed herds,
      respectively) and sister chromatid exchanges (SCEs) were found in both herds when
      compared with the control, and the differences were highly significant (P<0.001).
      No statistical differences were found when comparing the frequencies of aneuploid
      cells of exposed animals (16.4 and 17.8%) and control (17.9%). Furthermore, high
      levels of mortality and abnormal foetuses were recorded in one of the two farms
      when compared with the control.

PMID- 16434451
TI  - Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic
      ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with menstrual and
      reproductive abnormalities, insulin resistance, and obesity. OBJECTIVE: The
      objective of this study was to determine the prevalence of diagnosed PCOS and its
      association with cardiovascular risk factors. SETTING: The study is set in an
      integrated health care delivery system in northern California. PATIENTS: A total
      of 11,035 women with PCOS were identified by one or more outpatient diagnoses of
      PCOS using health plan databases. An age-matched sample of women without PCOS was
      also selected. OUTCOME MEASURES: Prevalence of PCOS and targeted cardiovascular
      risk factors [hypertension, dyslipidemia, diabetes mellitus, and body mass index
      (BMI)] were measured. RESULTS: During 2002-2004, the prevalence of diagnosed PCOS
      among female members aged 25-34 yr was 2.6% (95% confidence interval 1.6-1.7%).
      Women with diagnosed PCOS were more likely than those without PCOS to be obese
      [BMI > or = 30 mg/m(2); odds ratio (OR) 4.21, 3.96-4.47]. Furthermore, PCOS was
      associated with diabetes (OR 2.45, confidence interval 2.16-2.79), hypertension
      (OR 1.41, 1.31-1.51) and known dyslipidemia (OR 1.53, 1.39-1.68), even after
      adjusting for BMI and known confounders. Among women with PCOS, compared with
      whites, Blacks and Hispanics were more likely and Asians less likely to be obese;
      Asians and Hispanics were more likely to have diabetes; and Blacks were more
      likely and Hispanics less likely to have hypertension. CONCLUSIONS: Within a
      large, community-based population receiving health care, diagnosed PCOS was
      highly prevalent and associated with a much higher frequency of cardiovascular
      risk factors that varied by race/ethnicity. Our prevalence estimates likely
      underestimate the true prevalence of PCOS. Further studies are needed to explore
      racial/ethnic differences and the extent to which PCOS contributes to future
      cardiovascular risk.

PMID- 16434452
TI  - Pamidronate in children and adolescents with osteogenesis imperfecta: effect of
      treatment discontinuation.
AB  - CONTEXT: Cyclical iv pamidronate is a widely used symptomatic therapy of
      osteogenesis imperfecta (OI). What happens after treatment discontinuation is
      unknown. OBJECTIVE: The objective of this study was to assess the effect of
      pamidronate discontinuation in pediatric patients with moderate to severe OI
      types I, III, and IV. DESIGN: This was an open-label controlled and observational
      study in patients who had received pamidronate for more than 3 yr. SETTING: This
      study was performed at a pediatric metabolic bone research unit. PATIENTS: In the
      controlled study, 12 pairs of patients were matched for age, OI severity, and
      duration of pamidronate treatment. Pamidronate was stopped in one patient of each
      pair; the other continued to receive treatment. In the observational study, 38 OI
      patients were examined (mean age, 13.8 yr). INTERVENTION: The intervention was
      discontinuation of pamidronate treatment for 2 yr. MAIN OUTCOME MEASURES: The
      main outcome measures were lumbar spine bone mineral content and areal bone
      mineral density (aBMD), biochemical markers of bone metabolism, fracture
      incidence, and clinical evaluation. RESULTS: In the controlled study, bone
      resorption activity was higher after treatment discontinuation. Bone mineral
      content continued to increase in both groups. aBMD z-scores decreased in the
      untreated group, but increased in the continuation cohort. Fracture rates and
      functional status were similar between groups. In the observational study, bone
      resorption activity increased after treatment discontinuation, but remained
      significantly lower than in untreated OI patients. Bone mineral content and aBMD
      continued to increase, whereas aBMD z-scores decreased. Changes were faster in
      patients who continued growing. CONCLUSIONS: Bone metabolism is still suppressed
      2 yr after pamidronate discontinuation. Bone mass gains continue after treatment
      is stopped, but lumbar spine aBMD increases less than in healthy subjects. The
      size of these effects is growth dependent.

PMID- 16434453
TI  - Transient goiter enlargement after administration of 0.3 mg of recombinant human
      thyrotropin in patients with benign nontoxic nodular goiter: a randomized, double
      blind, crossover trial.
AB  - BACKGROUND: Recombinant human (rh) TSH, in doses from 0.01 to 0.9 mg, has been
      used to augment the effect of radioiodine ((131)I) therapy in patients with a
      benign nontoxic nodular goiter. Transient thyroid enlargement and thyrotoxicosis
      may be seen following (131)I therapy. AIM: The aim of the study was to
      investigate whether rhTSH per se causes goiter enlargement, until now an issue
      evaluated only in healthy nongoitrous subjects. METHODS: In random order, 10
      patients with nontoxic nodular goiter [mean 39.8 +/- 20.5 (sd) ml] received
      either 0.3 mg rhTSH or isotonic saline in a double-blinded crossover design.
      Thyroid volume (by ultrasound) and function were closely monitored during the
      following 28 d. RESULTS: Saline injection did not affect thyroid function or
      size. After rhTSH, median serum TSH increased from baseline 0.97 mU/liter (range
      0.39-1.56) to 37.0 mU/liter (range 18.5-55.0) at 24 h (P < 0.01), with a
      subsequent decline to subnormal levels at d 7. Mean free T(4) and free T(3)
      increased significantly from baseline to a maximum at 48 h. Twenty-four hours
      after rhTSH, the mean goiter volume was significantly increased by 9.8 +/- 2.3%
      (sem) (P = 0.01) and after 48 h by 24.0 +/- 5.1% (P = 0.002). The goiter
      enlargement had reverted at d 7. Nine patients had symptoms of hyperthyroidism
      and/or cervical compression after rhTSH, as opposed to one during placebo
      treatment (P < 0.02). CONCLUSIONS: A transient average goiter enlargement of up
      to 24% is seen after 0.3 mg rhTSH. This may lead to a significant cervical
      compression when used for augmentation of (131)I therapy in patients with goiter.
      The use of lower doses of rhTSH needs to be explored.

PMID- 16434454
TI  - Inverse relationship between luteinizing hormone and body mass index in
      polycystic ovarian syndrome: investigation of hypothalamic and pituitary
      contributions.
AB  - CONTEXT: Patients with polycystic ovarian syndrome (PCOS) have increased LH
      relative to FSH, but LH is modified by body mass index (BMI). OBJECTIVE: The
      objective of the study was to determine whether the impact of BMI on
      neuroendocrine dysregulation in PCOS is mediated at the hypothalamic or pituitary
      level. PARTICIPANTS/INTERVENTIONS/SETTING: Twenty-four women with PCOS across a
      spectrum of BMIs underwent frequent blood sampling, iv administration of GnRH (75
      ng/kg), and sc administration of the NAL-GLU GnRH antagonist (5 microg/kg) in the
      General Clinical Research Center at an academic hospital. MAIN OUTCOME MEASURES:
      LH pulse frequency and LH response to submaximal GnRH receptor blockade were used
      as measures of hypothalamic function; LH response to GnRH was used as a measure
      of pituitary responsiveness. RESULTS: BMI was negatively correlated with mean LH,
      LH/FSH, and LH pulse amplitude. There was no effect of BMI on LH pulse frequency.
      Percent inhibition of LH was decreased in PCOS, compared with normal women (53.9
      +/- 1.5 vs. 63.1 +/- 4.1, respectively; P < 0.01), suggesting an increase in the
      amount of endogenous GnRH, but was not influenced by BMI. Pituitary
      responsiveness to GnRH was inversely correlated with BMI (peak LH, R = -0.475, P
      < 0.02; and LH area under the curve R = -0.412, P < 0.02). CONCLUSIONS: LH pulse
      frequency and quantity of GnRH are increased in PCOS, but there is no influence
      of BMI on either marker of hypothalamic function. The pituitary response to a
      weight-based dose of GnRH is inversely related to BMI in PCOS. These studies
      suggest that the effect of BMI on LH is mediated at a pituitary and not a
      hypothalamic level in PCOS.

PMID- 16434455
TI  - Relationship among serum testosterone, sexual function, and response to treatment
      in men receiving dutasteride for benign prostatic hyperplasia.
AB  - CONTEXT: Although benign prostatic hyperplasia (BPH) is an androgen-dependent
      disorder, little is known regarding the influence of serum testosterone levels on
      sexual or prostate function or clinical response to dutasteride. OBJECTIVE: The
      objective of the study was to explore these relationships in a large cohort of
      men treated with dutasteride for BPH. DESIGN, SETTING, PATIENTS, AND OUTCOME
      MEASURES: Among 4254 men with BPH participating in 2-yr placebo-controlled
      dutasteride trials, 27% had a pretreatment serum testosterone less than 300
      ng/dl. These 1162 men were divided into seven groups based on their serum
      testosterone level (<150, 150-174, 175-199, 200-224, 225-249, 250-274, and 275
      299 ng/dl) and compared with men with normal baseline serum testosterone (BST; >
      or = 300 ng/dl). Questionnaires were used to assess sexual function, prostate
      specific antigen (PSA), and prostate volume to assess androgenic stimulation of
      the prostate and the American Urological Association Symptom Index to assess
      clinical responses. RESULTS: Although lower BST was associated with increased
      sexual dysfunction, this increase was not seen until BST was less than 225 ng/dl.
      There was no decrease in baseline PSA and prostate volume at low BST levels.
      Dutasteride was effective at decreasing PSA and prostate volume and improving BPH
      symptoms at all BST levels. CONCLUSIONS: In men with BPH, the frequency of sexual
      dysfunction increases at serum testosterone concentrations less than 225 ng/dl.
      However, PSA and prostate volume were similar at all testosterone levels,
      explaining why BPH can occur in men that would otherwise be considered
      hypogonadal. The fact that dutasteride is also effective in men with normal and
      low testosterone levels suggests that the high levels of 5alpha-reductase and
      dihydrotestosterone in the prostate allow the development and progression of
      prostatic hyperplasia, even at low circulating testosterone levels.

PMID- 16434456
TI  - Association of prolactin and its receptor gene regions with familial breast
      cancer.
AB  - CONTEXT: The contribution of prolactin (PRL) through its receptor (PRLR) to the
      pathogenesis and progression of human mammary tumors has received recent
      attention. OBJECTIVE: We investigated whether genetic variation in the PRL and
      PRLR genes is associated with the risk of breast cancer (BC). DESIGN: We
      conducted a case-control study with a total of seven single nucleotide
      polymorphisms (SNPs). SETTING: The study was conducted at an academic research
      laboratory and university clinics. PATIENTS AND OTHER PARTICIPANTS: A total of
      441 German familial, unrelated BC cases and 552 controls matched by age,
      ethnicity, and geographical region participated in the study. INTERVENTION(S):
      There were no interventions. MAIN OUTCOME MEASURES(S): SNP genotype and haplotype
      distributions and haplotype interactions were correlated with the risk of BC.
      RESULTS: Two SNPs (rs1341239 and rs12210179) within the PRL promoter regions were
      significantly associated with increased risk in homozygotes for the variant
      alleles [odds ratio (OR), 1.67 and 95% confidence interval (CI), 1.11-2.50; and
      OR, 2.09 and 95% CI, 1.23-3.52, respectively]. The PRL haplotype containing the
      variant alleles of the promoter SNPs increased significantly the risk of BC (OR
      1.42, 95%CI 1.07-1.90). A PRLR haplotype was associated with a significant
      decrease in BC risk (OR 0.69, 95% CI 0.54-0.89). An increasing number of PRL and
      PRLR risk haplotypes led to a significant trend of increasing risk for BC (chi(2)
      = 12.15; P = 0.007). CONCLUSIONS: Genetic variation in the PRL and PRLR genes was
      shown to influence BC risk. Additional studies are needed to further clarify the
      role of the PRL and PRLR genes in the risk of BC.

PMID- 16434457
TI  - Energy intake, ghrelin, and cholecystokinin after different carbohydrate and
      protein preloads in overweight men.
AB  - CONTEXT: Dietary proteins appear to be more satiating than carbohydrate. The
      mechanism and effect of protein and carbohydrate type are unclear. OBJECTIVE: The
      objective of the study is to compare the acute effect of different proteins and
      carbohydrates on indicators of appetite and appetite regulatory hormones. DESIGN:
      This is a randomized cross-over study of four orally consumed preloads followed
      by blood sampling (+15, 30, 45, 60, 90, 120, 180 min), then a buffet meal.
      SETTING: The study was carried out in an outpatient clinic. PATIENTS AND OTHER
      PARTICIPANTS: Nineteen overweight (body mass index 32.1 +/- 0.9 kg/m(2)) men
      participated. INTERVENTIONS: Liquid preloads (1 MJ) contained whey (55 g), casein
      (55 g), lactose (56 g), or glucose (56 g). MAIN OUTCOME MEASURES: Plasma ghrelin,
      cholecystokinin (CCK), insulin, glucose and amino acids, gastric emptying rate
      (plasma paracetamol), appetite rating (visual analog scale), and ad libitum
      energy intake were the main outcome measures. RESULTS: Energy intake was 10 +/-
      3% higher after the glucose preload compared with lactose and protein preloads (P
      < 0.05), which were predicted by ghrelin at 120 min (P < 0.05). CCK was 71 +/- 6%
      higher 90 min after the protein preloads compared with glucose and lactose (P <
      0.05), which predicted appetite at 180 min (P < 0.05). There was a small increase
      in branched chain amino acids after the whey preload compared with casein (P <
      0.01), but this was independent of appetite and energy intake. CONCLUSION: Acute
      appetite and energy intake are equally reduced after consumption of lactose,
      casein, or whey compared with glucose, which was consistent with differences in
      plasma ghrelin. Higher CCK responses after proteins correlated with satiety but
      did not affect energy intake.

PMID- 16434458
TI  - Prolonged salivary cortisol recovery in second-trimester pregnant women and
      attenuated salivary alpha-amylase responses to psychosocial stress in human
      pregnancy.
AB  - CONTEXT: The underlying biological mechanisms of stress-related pregnancy
      complications in humans are still poorly understood. Recent research on
      pharmacological or physical provocation procedures in pregnant women has resulted
      in inhomogeneous findings. Furthermore, no studies conducted so far have used a
      psychosocial stress paradigm at different stages of pregnancy. OBJECTIVE: The aim
      of this study was to identify endocrine, autonomic, and psychological responses
      to standardized psychosocial stress at different stages of pregnancy. DESIGN:
      Ninety healthy women (aged 21-37 yr), including 30 pregnant women at the
      beginning of the second trimester and 30 women at the beginning of the third
      trimester, as well as 30 nonpregnant women in the follicular phase of their
      menstrual cycle, underwent a psychosocial stress test. Salivary free cortisol,
      alpha-amylase, heart rate, and psychological parameters were repeatedly measured.
      RESULTS: Salivary cortisol recovery was significantly prolonged in second
      trimester pregnant women (P = 0.04). Cortisol and heart rate increases of both
      pregnant groups were shown to be comparable with those of the controls. alpha
      Amylase increases of both pregnant groups were markedly attenuated compared with
      nonpregnant women (P = 0.008). CONCLUSIONS: From these data, we conclude that, in
      contrast to pregnancy in rats, pregnancy in women does not result in a restraint
      of the hypothalamic-pituitary-adrenal axis to psychosocial stress. Furthermore,
      attenuated alpha-amylase stress response might reflect protective processes
      within the autonomic nervous system during pregnancy, whereas prolonged cortisol
      recovery during the beginning of second-trimester pregnancy might be associated
      with the vulnerability to stress-related pregnancy complications during this
      period of time.

PMID- 16434459
TI  - Serum gamma-glutamyl transpeptidase is a determinant of insulin resistance
      independently of adiposity in Pima Indian children.
AB  - CONTEXT: Elevated activities of serum enzymes, including alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT),
      have been associated with obesity and insulin resistance (IR). ALT is an
      independent predictor of type 2 diabetes mellitus (T2DM) in adult Pima Indians,
      and GGT predicts T2DM in other adult populations. OBJECTIVE: Our aim was to
      establish whether independent relationships exist between either adiposity or IR
      and hepatic enzymes in a group of Pima Indian children. SUBJECTS AND METHODS: In
      a cross-sectional study, 44 children (22 males and 22 females; 7-11 yr old) were
      measured for weight (WT), height, percent body fat, and serum activities of ALT,
      AST, and GGT. Body mass index (kilograms per meter squared) was calculated. IR
      was calculated from fasting plasma concentrations of glucose and insulin using
      the homeostasis model assessment (HOMA-IR). RESULTS: Hepatic enzymes were
      positively associated with obesity measures, fasting insulin, and HOMA-IR. GGT
      was additionally associated with serum lipids and white blood cell count. GGT,
      but not AST or ALT, was a significant determinant of HOMA-IR independently of
      age, sex, and WT, body mass index, or percent body fat. The model that accounted
      for the largest portion of the variance in HOMA-IR included WT (beta = 0.004; P =
      0.008) and GGT (beta = 0.20; P = 0.004; total R(2) = 0.62; P < 0.0001).
      CONCLUSION: Significant relationships between adiposity and hepatic enzyme
      activities exist during childhood in Pima Indians. Whether serum GGT activity
      predicts the development of T2DM in these children remains to be determined in
      follow-up studies.

PMID- 16434460
TI  - Associations of childhood and adulthood height and the components of height with
      insulin-like growth factor levels in adulthood: a 65-year follow-up of the Boyd
      Orr cohort.
AB  - CONTEXT: Taller individuals with longer legs have a higher risk of cancer but a
      lower risk of coronary heart disease. OBJECTIVE: We investigated whether
      childhood height and its components are associated with the IGF system in
      adulthood. DESIGN AND PARTICIPANTS: We analyzed data from 429 participants of the
      Boyd Orr cohort, for whom height measured in childhood (mean age, 7.4 yr) in 1937
      1939 could be related to levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2,
      and IGFBP-3 in adulthood (mean age, 71.1 yr). In 385 participants, measured
      height in adulthood could be related to IGF levels. RESULTS: In fully adjusted
      models (controlling for age, sex, socioeconomic factors, lifestyle, and body mass
      index), childhood height and its components were not associated with adult
      circulating IGF-I, IGF-II, or IGFBP-2 levels. IGFBP-3 was 85.5 ng/ml higher (95%
      confidence interval, -11.6 to 182.5; P = 0.08) per sd increase in childhood trunk
      length and 83.6 ng/ml lower (95% confidence interval, -10.3 to 177.5; P = 0.08)
      per sd increase in childhood leg/trunk ratio. Height in adulthood was not
      associated with IGF-I, IGF-II, or IGFBP-3 and was inversely associated with IGFBP
      2 (P = 0.05) after additionally controlling for childhood height. CONCLUSION:
      There was no evidence that associations of childhood height with cancer and
      coronary heart disease risk are mediated by IGF-I in adulthood. The
      anthropometric associations with IGFBP-2 and IGFBP-3 could be chance findings but
      warrant additional investigation. IGF levels in childhood may be more important
      determinants of long-term disease risk than adult levels.

PMID- 16434461
TI  - The diagnostic value for differentiated thyroid carcinoma metastases of
      thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration
      biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg
      antibodies.
AB  - OBJECTIVE: Serum thyroglobulin (Tg) is the marker of differentiated thyroid
      carcinoma (DTC) after total thyroidectomy, but its value is limited by the
      interference of anti-Tg antibodies (TgAb). Detection of Tg in fine-needle
      aspiration biopsy (Tg-FNAB) washout fluid is used to identify neck DTC
      recurrences/metastases, but the interference of serum TgAb in this procedure is
      unknown. PATIENTS AND METHODS: Seventy-three patients (41 after surgery for
      thyroid cancer and 32 with thyroid nodules) evaluated for suspicious cervical
      lymph nodes were retrospectively reviewed. Tg was assayed by immunoradiometric
      assay or chemiluminescent assay in ultrasound-guided FNAB used for cytology.
      Serum TgAb were detected by passive agglutination or chemiluminescent assay. On
      the basis of preliminary data obtained in lymphadenitis, Tg-FNAB more than 36
      ng/ml and more than 1.7 ng/ml (in the presence or absence of thyroid gland,
      respectively) was considered as indicative of metastasis. RESULTS: In 51 TgAb
      negative patients, Tg-FNAB was positive in 15 (12 with malignant and three with
      nondiagnostic cytology), all with histologically confirmed DTC metastases. Of the
      remaining 36 patients with negative Tg-FNAB, 30 had nonsuspicious and six had
      suspicious cytology. Histology of the latter showed four undifferentiated thyroid
      cancer metastases and two lymphadenitis. In 22 TgAb-positive patients, Tg-FNAB
      was positive in 14 (12 with malignant and two with nondiagnostic cytology), all
      with histologically confirmed DTC metastases. CONCLUSIONS: Clinical performance
      of Tg-FNAB appears to be not substantially affected by TgAb, and this procedure
      remains superior to cytology in the identification of DTC neck metastases.
      However, cytology should always be performed because, irrespective of TgAb, Tg is
      undetectable in FNAB from undifferentiated metastases.

PMID- 16434462
TI  - Cardiovascular risk factors in healthy women with previous gestational
      hypertension.
AB  - CONTEXT: Epidemiological studies indicate that gestational hypertension (Gh)
      during pregnancy is associated with increased risk of cardiovascular disease in
      later life. However, it is unclear whether particular metabolic and hemodynamic
      characteristics are related to this risk. OBJECTIVE: The objective of this study
      was to investigate endothelial function and carbohydrate and lipid metabolism in
      healthy, normotensive women with previous pregnancy complicated by Gh. DESIGN,
      SETTING, AND PARTICIPANTS: Brachial artery flow-mediated dilatation (FMD;
      endothelium dependent) and nitroglycerin-induced dilatation (endothelium
      independent) were measured in 15 subjects with previous Gh and in 15 controls
      with previous normal pregnancies. Lipid panel, glucose, insulin, homocysteine,
      and androgens were also measured. RESULTS: FMD was significantly reduced in women
      with previous Gh compared with controls (P < 0.0001), whereas nitroglycerin
      induced dilatation was comparable in both groups. Gh women showed increased
      fasting insulin (P = 0.011), insulin resistance measured by homeostasis model
      assessment (P = 0.018), free fatty acids (P = 0.0018), and testosterone (P =
      0.0012) and decreased high-density lipoprotein cholesterol (P = 0.0017) compared
      with controls. Across all subjects, FMD showed a strong independent negative
      correlation with testosterone and homeostasis model assessment and a positive
      correlation with high-density lipoprotein cholesterol (r = -0.60, P = 0.0003; r =
      -0.43, P = 0.016; and r = 0.58, P = 0.0005, respectively). CONCLUSIONS:
      Endothelial dysfunction and early alteration of carbohydrate and lipid metabolism
      are present in otherwise healthy women with previous Gh. These abnormalities
      along with a relative hyperandrogenism could explain, at least in part, the
      increased risk for cardiovascular disease in later life in these women.

PMID- 16434463
TI  - Free fatty acids increase androgen precursors in vivo.
AB  - CONTEXT: There is considerable evidence that metabolic factors such as insulin
      resistance may induce hyperandrogenemia in polycystic ovary syndrome. However,
      other metabolic factors such as free fatty acids (FFAs) may also contribute to
      androgen excess. OBJECTIVE: The objective was to study effects of FFAs on adrenal
      production of androgen precursors in vivo. DESIGN AND PARTICIPANTS: We
      investigated eight healthy young men, because male individuals produce the
      androgen precursors dehydroepiandrosterone (DHEA), DHEA sulfate, and
      androstenedione predominantly in the adrenal gland. A randomized controlled
      crossover trial was performed. INTERVENTION: After a 10-h overnight fast, 20%
      lipid/heparin or saline/heparin infusion was given at a rate of 1.5 ml/min. Four
      hours after start of lipid infusion, a euglycemic hyperinsulinemic clamp was
      performed. MAIN OUTCOME MEASURES: DHEA, androstenedione, 17-OH-progesterone,
      testosterone, estrone, LH, FSH, ACTH, and cortisol were measured. RESULTS: The
      adrenal androgen precursors DHEA and androstenedione showed a circadian decline
      during saline/heparin infusion (P < 0.05 vs. baseline, respectively), whereas no
      significant changes were observed during lipid/heparin infusion (P = not
      significant vs. baseline, respectively). Correspondingly, DHEA and
      androstenedione values were significantly elevated during lipid compared with
      saline infusion (P < 0.05, respectively), and areas under curve of both androgen
      precursors were significantly increased with lipid compared with saline infusion.
      Notably, all changes were detected before induction of insulin resistance.
      CONCLUSIONS: This study demonstrates that FFAs increase production of androgen
      precursors in vivo in men. These data tentatively suggest that hyperandrogenemia
      in polycystic ovary syndrome may be induced, at least in part, by elevated FFAs.

PMID- 16434465
TI  - The performance of laboratories analysing heavy metals in the Workplace Analysis
      Scheme for Proficiency (WASP).
AB  - This paper discusses the proficiency of laboratories analysing identical test
      samples representative of metals in air in the Workplace Analysis Scheme for
      Proficiency (WASP) and the variability of results from laboratories used to
      assess personal exposure in the workplace. Over 11 years, the performance of
      laboratories has significantly improved for lead, cadmium and chromium.
      Laboratories show better agreement when using inductively coupled plasma-atomic
      emission spectroscopy (ICP-AES) than flame atomic absorption spectroscopy (FAAS)
      when analysing chromium, but not when analysing lead and cadmium. Data from the
      proficiency testing scheme show that for a customer to have confidence that a
      measurement value does not exceed the workplace exposure limit the analytical
      result would have to be <134 microg m(-3) for lead and 23 microg m(-3) for
      cadmium for an 8 h sample and 129 microg m(-3) for lead, 21 microg m(-3) for
      cadmium and 429 microg m(-3) for chromium for a 4 h sample (for samples with
      relatively soluble matrices), before considering the further uncertainties due to
      sampling. The performance criterion for satisfactory performance (+/-8.3%) was
      found to be appropriate as long as laboratories participated consecutively in all
      rounds. Estimates of the overall uncertainty of results from ICP-AES and FAAS
      analysis were shown to meet the criteria in EN482. Samples from some types of
      workplace environments are more difficult than the WASP test material to dissolve
      into solution, so it is expected that estimates of uncertainty are larger for
      less soluble analytes and matrices. WASP has now initiated a programme to help
      laboratories assess their performance with more complex matrices.

PMID- 16434466
TI  - Determination of airborne isocyanates generated during the thermal degradation of
      car paint in body repair shops.
AB  - Polyurethanes are widely used in car paint formulations. During thermal
      degradation, such polymeric systems can generate powerful asthmatic sensitizing
      agents named isocyanates. In body repair shops, the thermal degradation of car
      paint can occur during abrasive processes that generate enough heat to involve
      release of isocyanates in air. An environmental monitoring study was performed in
      two body repair training schools and in a body repair shop to evaluate the
      workers' exposure to isocyanates during cutting, grinding and orbital sanding
      operations. For sampling, cassettes containing two 1-(2-methoxyphenyl)piperazine
      (MOPIP)-coated glass fiber filters (MFs) ( approximately 5 mg of MOPIP per
      filter) and bubblers containing 15 ml of MOPIP solution in toluene (1.0 mg ml(
      1)) backed at the outlet with cassettes containing two MFs were used. Tandem mass
      spectrometry was used to analyze the MOPIP derivatives of isocyanic acid (HNCO),
      all the linear aliphatic isocyanates ranging from methyl isocyanate (Me-i) to
      hexyl isocyanate, all the alkenyl isocyanates ranging from propylene isocyanate
      to hexylene isocyanate, 1,6-hexamethylene diisocyanate (HDI), trans- and cis
      isophorone diisocyanate (IPDI), 2,4- and 2,6-toluene diisocyanate (TDI), 2,4'-;
      2,2'- and 4,4'-methylenediphenyl diisocyanate (MDI), phenyl isocyanate (Ph-i) and
      p-toluene isocyanate (p-Tol-i). The instrumental detection limits (LOD) were in
      the 0.13-0.75 microg of NCO per m(3) range for 15 l air samples converted into 3
      ml liquid samples. The isocyanate concentrations detected in the workers'
      breathing zone were in the 1.07-9.80 microg of NCO per m(3) range for cutting,
      0.63-3.62 microg of NCO per m(3) range for grinding and 0-1.29 microg of NCO per
      m(3) range for sanding. However, a rapid decrease of the isocyanate concentration
      was observed while moving away from the emission source. Among the isocyanates
      detected the most abundant were the monomers (MDI, HDI, TDI and IPDI) and Me-i.

PMID- 16434464
TI  - Insulin sensitivity during combined androgen blockade for prostate cancer.
AB  - CONTEXT: GnRH agonists markedly increase fat mass in men with prostate cancer,
      but little is known about the effects of treatment on insulin sensitivity.
      OBJECTIVE: The objective of the study was to assess the effects of short-term
      GnRH agonist treatment on insulin sensitivity. DESIGN: This was a prospective 12
      wk study. SETTING: The study was conducted at a general clinical research center.
      PATIENTS OR OTHER PARTICIPANTS: We studied 25 men with locally advanced or
      recurrent prostate cancer, no radiographic evidence of metastases, no history of
      diabetes mellitus, and no evidence of diabetes mellitus at baseline visit.
      INTERVENTION: Leuprolide depot and bicalutamide were used in the study. MAIN
      OUTCOME MEASURES: Oral glucose tolerance tests and body composition assessment by
      dual-energy x-ray absorptiometry were performed at baseline and wk 12. The
      primary study outcome was change in insulin sensitivity index. RESULTS: Mean (+/-
      se) percentage fat body mass increased by 4.3 +/- 1.3% from baseline to wk 12 (P
      = 0.002). Insulin sensitivity index decreased by 12.9 +/- 7.6% (P = 0.02).
      Insulin sensitivity by homeostatic model assessment decreased by 12.8 +/- 5.9% (P
      = 0.02). Fasting plasma insulin levels increased by 25.9 +/- 9.3% (P = 0.04).
      Mean glycosylated hemoglobin also increased significantly (P < 0.001).
      CONCLUSIONS: Short-term treatment with leuprolide and bicalutamide significantly
      increased fat mass and decreased insulin sensitivity in men with prostate cancer.
      These observations suggest that GnRH agonists may increase the risk of diabetes
      mellitus and cardiovascular disease in older men.

PMID- 16434467
TI  - Secular stroke trends: early life factors and future prospects.
AB  - Stroke mortality rates have declined during the second half of the 20th century
      in developed countries. Possible reasons for this include preventive measures,
      recent environmental changes impacting on adult health risks, and more distant
      environmental influences on childhood health. Data from a number of populations
      in Europe and the USA suggest that a decrease in early life blood pressure,
      occurring since the beginning of the 20th century, may have been an important
      determinant of declining stroke incidence rates and cardiovascular disease
      mortality in general. Advances in stroke epidemiology are increasing the accuracy
      of case ascertainment, and neuroimaging refinements (particularly MRI) are
      improving the accuracy of stroke type and subtype diagnoses. Although some risk
      factors are common to ischaemic and haemorrhagic stroke, there is accumulating
      evidence of differing aetiology. There is also an increasing recognition that
      early life factors may influence stroke risk. Despite the encouraging decline in
      stroke incidence, there is evidence of a recent increase in mean blood pressure
      in young people observed in the USA and UK, prompting concern that favourable
      trends in stroke risk may not be maintained. Reducing early life blood pressure
      in a population and delaying the onset of hypertension, along with effective
      measures to combat obesity, are required to avoid a reversal in stroke incidence
      trends in developed countries, and to prevent the anticipated increase in the
      burden of stroke in developing countries.

PMID- 16434468
TI  - Collett's snake (Pseudechis colletti) envenoming in snake handlers.
AB  - BACKGROUND: Collett's snake (Pseudechis colletti) is a member of the black snake
      genus and occurs in a warm temperate to sub-tropical region of central
      Queensland, Australia. There are no reports of bites occurring in the wild, and
      bites were previously thought to cause only minor effects. They are a popular
      snake among zoos and exotic snake keepers. AIM: To investigate the clinical
      effects of severe envenoming by Collett's snake, and possible treatment options.
      DESIGN: Case series. METHODS: Clinical and laboratory features are described for
      six bites, all in snake handlers. RESULTS: All six bites were from captive
      snakes, resulting in severe envenoming in four. Two patients were treated early
      with black snake antivenom, and only developed an anticoagulant coagulopathy and
      mild myolysis. Two developed anticoagulant coagulopathy and severe rhabdomyolysis
      associated with acute renal failure, requiring haemodialysis; both received
      antivenom >10 h after the bite, and initially received minimal fluid replacement.
      Other effects included thrombocytopenia, non-immune haemolytic anaemia and a
      marked leukocytosis. DISCUSSION: Collett's snake envenoming is characterized by
      early generalized systemic effects (nausea, vomiting, abdominal pain, diarrhoea
      and headache) and an anticoagulant coagulopathy, followed in some cases by
      rhabdomyolysis and acute renal failure in untreated patients within 24 h. Early
      initiation of fluid therapy and treatment with black snake antivenom should be
      undertaken in all envenomed patients.

PMID- 16434469
TI  - Neurological involvement in patients with rheumatic disease.
AB  - Patients with multi-system rheumatic conditions may have disease affecting the
      central and peripheral nervous systems. Early assessment is often helpful in
      averting the development of serious complications, which in some conditions can
      be prevented by the prompt institution of treatment. We review the spectrum of
      neurological disease in patients with a rheumatological diagnosis. The wide
      variety of associated neurological complications is discussed in the context of
      specific rheumatic conditions, varying from spinal cord involvement in rheumatoid
      arthritis, to neuropsychiatric involvement in systemic lupus erythematosus and
      neurological sequelae in vasculitic disorders. We discuss diagnostic criteria and
      recommended management options (where available), and describe the role of new
      tools such as functional brain imaging in the diagnosis and monitoring of
      disease. We also discuss the potential for development of neurological
      complications from the use of anti-rheumatic drugs.

PMID- 16434470
TI  - Enigma, a mitochondrial protein affecting lifespan and oxidative stress response
      in Drosophila.
AB  - Deregulation of energy metabolism by external interventions or mutations in
      metabolic genes can extend lifespan in a wide range of species. We describe
      mutations in Drosophila melanogaster that confer resistance to oxidative stress
      and display a longevity phenotype. These phenotypes are associated with molecular
      lesions in a hitherto uncharacterized gene we named Enigma. We show that Enigma
      encodes a mitochondrial protein with homology to enzymes of the beta-oxidation of
      fatty acids and that mutations in this locus affect lipid homeostasis. Our
      analysis provides further support to the notion that lipid metabolism may play a
      central role in metazoan lifespan regulation.

PMID- 16434471
TI  - Innate antiviral response targets HIV-1 release by the induction of ubiquitin
      like protein ISG15.
AB  - The goal of this study was to elucidate the molecular mechanism by which type I
      IFN inhibits assembly and release of HIV-1 virions. Our study revealed that the
      IFN-induced ubiquitin-like protein ISG15 mimics the IFN effect and inhibits
      release of HIV-1 virions without having any effect on the synthesis of HIV-1
      proteins in the cells. ISG15 expression specifically inhibited ubiquitination of
      Gag and Tsg101 and disrupted the interaction of the Gag L domain with Tsg101, but
      conjugation of ISG15 to Gag or Tsg101 was not detected. The inhibition of Gag
      Tsg101 interaction was also detected in HIV-1 infected, IFN-treated cells.
      Elimination of ISG15 expression by small interfering RNA reversed the IFN
      mediated inhibition of HIV-1 replication and release of virions. These results
      indicated a critical role for ISG15 in the IFN-mediated inhibition of late stages
      of HIV-1 assembly and release and pointed to a mechanism by which the innate
      antiviral response targets the cellular endosomal trafficking pathway used by HIV
      1 to exit the cell. Identification of ISG15 as the critical component in IFN
      mediated inhibition of HIV-1 release advances the understanding of the IFN
      mediated inhibition of HIV-1 replication and uncovers a target for the anti HIV-1
      therapy.

PMID- 16434473
TI  - Networks of gold nanoparticles and bacteriophage as biological sensors and cell
      targeting agents.
AB  - Biological molecular assemblies are excellent models for the development of
      nanoengineered systems with desirable biomedical properties. Here we report an
      approach for fabrication of spontaneous, biologically active molecular networks
      consisting of bacteriophage (phage) directly assembled with gold (Au)
      nanoparticles (termed Au-phage). We show that when the phage are engineered so
      that each phage particle displays a peptide, such networks preserve the cell
      surface receptor binding and internalization attributes of the displayed peptide.
      The spontaneous organization of these targeted networks can be manipulated
      further by incorporation of imidazole (Au-phage-imid), which induces changes in
      fractal structure and near-infrared optical properties. The networks can be used
      as labels for enhanced fluorescence and dark-field microscopy, surface-enhanced
      Raman scattering detection, and near-infrared photon-to-heat conversion.
      Together, the physical and biological features within these targeted networks
      offer convenient multifunctional integration within a single entity with
      potential for nanotechnology-based biomedical applications.

PMID- 16434472
TI  - Zinc supplementation of young men alters metallothionein, zinc transporter, and
      cytokine gene expression in leukocyte populations.
AB  - An effective measure to assess zinc status of humans has remained elusive, in
      contrast to iron, where a number of indicators of metabolism/function are
      available. Using monocytes, T lymphocytes, and granulocytes isolated by magnetic
      sorting and dried blood spots (DBS) derived from 50 mul of peripheral blood, we
      evaluated the response of metallothionein (MT), zinc transporter, and cytokine
      genes to a modest (15 mg of Zn per day) dietary zinc supplement in human
      subjects. Transcript abundance was measured by quantitative real-time RT-PCR (QRT
      PCR). Zinc supplementation increased MT mRNA abundance by up to 2-fold in RNA
      from leukocyte subsets, and 4-fold in RNA from DBS. Transcript levels for the
      zinc transporter genes ZnT1 and Zip3 were increased and decreased, respectively,
      by zinc supplementation. Expression of the ZnT and Zip genes among leukocyte
      subsets differ by up to 270-fold. Monocytes and granulocytes from supplemented
      subjects were activated by LPS, whereas T lymphocytes were activated by mimicking
      antigen presentation. With zinc consumption, TNF-alpha and IL-1beta expression
      was greater in activated monocytes and granulocytes, and IFN-gamma mRNA levels
      were higher in activated T lymphocytes. These studies show that QRT-PCR is a tool
      to reliably measure transcript abundance for nutritionally responsive genes in
      human subjects, and that a small sample of whole dried blood, when appropriately
      collected, can be used as the source of total RNA for QRT-PCR analysis. The
      results obtained also show that zinc supplementation of human subjects programs
      specific leukocytic subsets to show enhanced cytokine expression upon activation
      by stimulators of immunity.

PMID- 16434474
TI  - Profile of Chikashi Toyoshima.

PMID- 16434475
TI  - Armadillo-related proteins promote lateral root development in Arabidopsis.
AB  - Armadillo/beta-catenin and related proteins have important functions during
      animal and Dictyostelium development, regulating cell differentiation,
      proliferation, and adhesion. Armadillo-repeat-containing proteins also exist in
      plants, but the majority have unknown roles. The Arabidopsis genes that show
      greatest sequence homology to Armadillo/beta-catenin are called ARABIDILLO-1 and 
      2. Here, we demonstrate that ARABIDILLO-1 and -2 promote lateral root
      development. arabidillo-1/-2 mutants form fewer lateral roots, and ARABIDILLO-1
      overexpressing lines produce more lateral roots than wild-type seedlings.
      ARABIDILLO-yellow fluorescent protein fusions are nuclear. ARABIDILLO proteins
      contain an F-box motif, and thus may target other proteins for proteasomal
      degradation. Overexpression of ARABIDILLO-1 protein fragments, including F-box
      fragments, in wild-type seedlings reduces lateral root formation to the level of
      the arabidillo-1/-2 mutant. We have shown that plant beta-catenin-related
      proteins regulate root development. We suggest that ARABIDILLO proteins may
      target an inhibitor of lateral root development for degradation and propose that
      Arabidopsis beta-catenin-related proteins define a previously uncharacterized
      pathway that promotes root branching.

PMID- 16434477
TI  - APRO4 negatively regulates Src tyrosine kinase activity in PC12 cells.
AB  - The Src nonreceptor tyrosine kinase plays an important role in multiple
      signalling pathways that regulate several cellular functions including
      proliferation, differentiation and transformation. The activity of Src is tightly
      regulated in vivo and can be modulated by interactions of its SH2 and SH3 domains
      with high-affinity ligands. APRO4 (anti-proliferative 4) belongs to a new
      antiproliferative gene family involved in the negative control of the cell cycle.
      This report shows that APRO4 associates with Src via its C-terminal proline-rich
      domain, and downregulates Src kinase activity. Moreover, overexpression of APRO4
      leads to inhibition of neurite outgrowth and Ras/MAP kinase signalling in PC12
      cells. Furthermore, the kinetics of endogenous Src inactivation correlates with
      an increase in endogenous APRO4 co-immunoprecipitation in FGF-stimulated PC12
      cells. Finally, downregulation of endogenous APRO4 by expression of antisense RNA
      induces the activation of Src and spontaneous formation of neurites in PC12
      cells. Therefore, by controlling the basal threshold of Src activity, APRO4
      constitutes an important negative regulatory mechanism for Src-mediated
      signalling.

PMID- 16434478
TI  - Regulation of mitochondria distribution by RhoA and formins.
AB  - The distribution of mitochondria is strictly controlled by the cell because of
      their vital role in energy supply, regulation of cytosolic Ca2+ concentration and
      apoptosis. We employed cultured mammalian CV-1 cells and Drosophila BG2-C2
      neuronal cells with enhanced green fluorescent protein (EGFP)-tagged mitochondria
      to investigate the regulation of their movement and anchorage. We show here that
      lysophosphatidic acid (LPA) inhibits fast mitochondrial movements in CV-1 cells
      acting through the small GTPase RhoA. The action of RhoA is mediated by its
      downstream effectors: formin-homology family members mDia1 in mammalian cells and
      diaphanous in Drosophila. Overexpression of constitutively active mutant forms of
      formins leads to dramatic loss of mitochondrial motility and to their anchorage
      to actin microfilaments. Conversely, depletion of endogenous diaphanous protein
      in BG2-C2 cells by RNA interference (RNAi) stimulates the mitochondrial movement.
      These effects are not simply explained by increased cytoplasm viscosity resulting
      from an increased F-actin concentration since stimulators of Arp2/3-dependent
      actin polymerization and jasplakinolide do not cause inhibition. The observed
      effects are highly specific to mitochondria since perturbations of diaphanous or
      mDia1 have no effect on movement of other membrane organelles. Thus,
      mitochondrial movement is controlled by the small GTPase RhoA and this control is
      mediated by formins.

PMID- 16434476
TI  - Emotion enhances remembrance of neutral events past.
AB  - Emotional events are bestowed with special prominence in memory. This may reflect
      greater attention oriented to these events during encoding, and/or enhancement of
      memory consolidation after emotional events have passed. Here we show invoked
      emotional arousal results in a retrograde enhancement of long-term memory,
      determining what will later be remembered or forgotten. Subjects saw pictures of
      neutral faces and houses followed by emotionally arousing scenes at varying
      intervals. Self-reported emotional arousal responses predicted a retrograde
      enhancement of memory for preceding neutral events in a 1-week delayed
      recognition memory test. At longer picture-scene intervals, no enhancement was
      found, implicating a critical window in which emotional arousal must occur for
      retrograde memory enhancement. Postencoding manipulation of emotional arousal
      specifically enhanced conscious recollection rather than familiarity-based
      discrimination. An additional study revealed no retrograde enhancement for
      pictures preceding highly memorable, but nonarousing, distinctive scenes. These
      findings indicate an important role for emotional arousal in the postencoding
      enhancement of episodic memory consolidation.

PMID- 16434479
TI  - ABCB1/MDR1 gene determines susceptibility and phenotype in ulcerative colitis:
      discrimination of critical variants using a gene-wide haplotype tagging approach.
AB  - Several lines of evidence suggest a role for the multidrug resistance gene
      (ABCB1/MDR1) and its product, P-glycoprotein 170, in the pathogenesis of
      inflammatory bowel disease (IBD). In addition, P-glycoprotein activity determines
      bioavailability of many drugs used regularly in many medical specialties, and
      ABCB/MDR1 variation appears to be a critical pharmacogenetic determinant. We have
      utilized a gene-wide haplotype tagging approach to further define the identity of
      germ-line variations in the ABCB1/MDR1 gene contributing to IBD susceptibility.
      Six haplotype tagging single nucleotide polymorphisms (tSNPs) representing the
      haplotypic variations of the ABCB1/MDR1 gene were identified initially following
      the characterization of the haplotype structure of this gene in 24 Centre d'Etude
      du Polymorphisme Humain Caucasian trios. Genotyping was performed in 249
      ulcerative colitis (UC) and 179 Crohn's disease (CD) patients and 260 healthy
      controls. Using log-likelihood analysis, we observed a highly significant
      association between the common haplotypes and UC (P=4.22 x 10(-7)) but not CD
      (P=0.22). This significant association was critically dependent on one tSNP,
      intronic variant rs3789243. All haplotypes with this variant retained a highly
      significant association (P=3.2 x 10(-7)-3.6 x 10(-12)), whereas significance was
      lost when rs3789243 was dropped in systematic haplotypic analysis. The effect of
      this tSNP was independent of C3435T SNP, previously suggested to be the critical
      variant in disease susceptibility and drug transport. The association with UC was
      shown to be strongest with the phenotype of extensive disease (P=1.7 x 10(-7)).
      This 'candidate gene' approach provides compelling evidence to support the
      contribution of the ABCB1/MDR1 gene in determining risk to UC but not to CD and
      provides new insights into the localization of the critical susceptibility
      determinants within the gene. In addition, these findings have potentially
      important implications in the application of pharmacogenetics across a range of
      common diseases, including HIV, epilepsy and colorectal cancer.

PMID- 16434480
TI  - The DFNB31 gene product whirlin connects to the Usher protein network in the
      cochlea and retina by direct association with USH2A and VLGR1.
AB  - Mutations in the DFNB31 gene encoding the PDZ scaffold protein whirlin are
      causative for hearing loss in man and mouse. Whirlin is known to be essential for
      the elongation process of the stereocilia of sensory hair cells in the inner ear,
      though its complete spatial and temporal expression patterns remained elusive.
      Here, we demonstrate that, in embryonic development, the gene is not only
      expressed in the inner ear, but also in the developing brain and the retina.
      Various isoforms of whirlin are widely and differentially expressed, and we
      provide evidence that whirlin directly associates with USH2A isoform b and
      VLGR1b, two proteins that we previously reported to be part of the Usher protein
      interactome. These proteins co-localize with whirlin at the synaptic regions of
      both photoreceptor cells and outer hair cells in the cochlea. These findings
      indicate that whirlin is part of a macromolecular PDZ protein scaffold that
      functions in the organization of the pre- and/or postsynaptic side of
      photoreceptor and hair cell synapses. Whirlin might be involved in synaptic
      adhesion through interaction with USH2A and VLGR1b as well as in synaptic
      development as suggested by its spatial and temporal expression patterns. In
      addition, we demonstrate that whirlin, USH2A and Vlgr1b co-localize at the
      connecting cilium and the outer limiting membrane of photoreceptor cells and in
      spiral ganglion neurons of the inner ear. Our data show that whirlin is connected
      to the dynamic Usher protein interactome and indicate that whirlin has a
      pleiotropic function in both the retina and the inner ear.

PMID- 16434481
TI  - DNA copy-number analysis in bipolar disorder and schizophrenia reveals
      aberrations in genes involved in glutamate signaling.
AB  - Using bacterial artificial chromosome (BAC) array comparative genome
      hybridization (aCGH) at approximately 1.4 Mbp resolution, we screened post-mortem
      brain DNA from bipolar disorder cases, schizophrenia cases and control
      individuals (n=35 each) for DNA copy-number aberrations. DNA copy number is a
      largely unexplored source of human genetic variation that may contribute risk for
      complex disease. We report aberrations at four loci which were seen in affected
      but not control individuals, and which were verified by quantitative real-time
      PCR. These aberrant loci contained the genes encoding EFNA5, GLUR7, CACNG2 and
      AKAP5; all brain-expressed proteins with known or postulated roles in neuronal
      function, and three of which (GLUR7, CACNG2 and AKAP5) are involved in glutamate
      signaling. A second cohort of psychiatric samples was also tested by quantitative
      PCR using the primer/probe sets for EFNA5, GLUR7, CACNG2 and AKAP5, and samples
      with aberrant copy number were found at three of the four loci (GLUR7, CACNG2 and
      AKAP5). Further scrutiny of these regions may reveal insights into the etiology
      and genetic risk factors for these complex psychiatric disorders.

PMID- 16434482
TI  - Podocalyxin variants and risk of prostate cancer and tumor aggressiveness.
AB  - We previously reported linkage of a prostate cancer tumor aggressiveness locus to
      chromosome 7q32-q33, a region also associated with a high frequency of allelic
      imbalance in prostate tumors. The smallest region of allelic imbalance contains
      the podocalyxin-like (PODXL) gene, which we evaluate here as a candidate prostate
      cancer aggressiveness gene mapping to 7q32-q33. DNA from probands of linked
      families was examined for germ-line mutations in PODXL. A variable in-frame
      deletion, four missense variants and two nonsense variants were identified in
      linked men. Variants that affected amino acid sequence were further evaluated for
      association with risk of prostate cancer and tumor aggressiveness in a family
      based case-control population (439 cases and 479 sibling controls). The presence
      of any single in-frame deletion was positively associated with prostate cancer
      [odds ratio (OR)=2.14, 95% confidence interval (95%CI)=1.09-4.20, P=0.03] and the
      presence of two copies of any deletion further increased risk (OR=2.58,
      95%CI=1.23-5.45, P=0.01). This finding was strengthened when stratifying among
      men with more aggressive disease (high grade or stage): OR=3.04 for one deletion
      (95%CI=1.01-9.15) and OR=4.42 for two deletions (95%CI=1.32-14.85, P=0.02). A
      weak positive association was also observed between prostate cancer risk and
      PODXL variant 340A (in linkage disequilibrium with another variant, 587T)
      (OR=1.48, 95%CI=1.02-2.14, P=0.04). These results implicate PODXL as a candidate
      prostate cancer tumor aggressiveness gene mapping to chromosome 7q32-q33.

PMID- 16434484
TI  - Dysregulated monocyte iron homeostasis and erythropoietin formation in patients
      with anemia of chronic disease.
AB  - Anemia of chronic disease (ACD) is frequently found in patients with chronic
      immune activation. Since most studies on ACD pathophysiology were performed with
      cell culture or animal models but not in humans, we examined 37 ACD patients
      suffering from autoimmune diseases or infections, 10 subjects with iron
      deficiency anemia (IDA), 10 anemic patients with hereditary spherocytosis (HS),
      and 27 age-matched controls. Although hemoglobin concentrations were comparable
      between ACD and IDA patients, the latter presented with significantly higher
      serum erythropoietin concentrations than ACD patients. The significant negative
      correlation between erythropoietin and hemoglobin levels observed in IDA patients
      was also found in a group of anemic but not hypoferremic hereditary spherocytosis
      subjects, but not in ACD patients. Increased serum concentrations of the hepcidin
      precursor prohepcidin were paralleled by a decreased expression of the iron
      exporter ferroportin in circulating monocytes of ACD patients. In the latter
      cells, increased amounts of the iron storage protein ferritin and a reduced
      activity of iron-regulatory protein indicated monocyte iron accumulation. Our
      data indicate that hypoferremia in ACD may result from downregulation of
      ferroportin expression by hepcidin and cytokines with subsequent iron retention
      in monocytes. Together with a diminished erythropoietin formation, the impaired
      iron recirculation from monocytes may be central in the pathophysiology of ACD in
      humans.

PMID- 16434483
TI  - Polyglutamine expansion causes neurodegeneration by altering the neuronal
      differentiation program.
AB  - Huntington's disease (HD) and spinocerebellar ataxia type 7 (SCA7) belong to a
      group of inherited neurodegenerative diseases caused by polyglutamine (polyQ)
      expansion in corresponding proteins. Transcriptional alteration is a unifying
      feature of polyQ disorders; however, the relationship between polyQ-induced gene
      expression deregulation and degenerative processes remains unclear. R6/2 and R7E
      mouse models of HD and SCA7, respectively, present a comparable retinal
      degeneration characterized by progressive reduction of electroretinograph
      activity and important morphological changes of rod photoreceptors. The retina,
      which is a simple central nervous system tissue, allows correlating functional,
      morphological and molecular defects. Taking advantage of comparing polyQ-induced
      degeneration in two retina models, we combined gene expression profiling and
      molecular biology techniques to decipher the molecular pathways underlying polyQ
      expansion toxicity. We show that R7E and R6/2 retinal phenotype strongly
      correlates with loss of expression of a large cohort of genes specifically
      involved in phototransduction function and morphogenesis of differentiated rod
      photoreceptors. Accordingly, three key transcription factors (Nrl, Crx and Nr2e3)
      controlling rod differentiation genes, hence expression of photoreceptor specific
      traits, are down-regulated. Interestingly, other transcription factors known to
      cause inhibitory effects on photoreceptor differentiation when mis-expressed,
      such as Stat3, are aberrantly re-activated. Thus, our results suggest that
      independently from the protein context, polyQ expansion overrides the control of
      neuronal differentiation and maintenance, thereby causing dysfunction and
      degeneration.

PMID- 16434485
TI  - DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and
      modulates cytokine production.
AB  - The generation of pathogen-specific immune responses is dependent on the
      signaling capabilities of pathogen-recognition receptors. DC-SIGN is a C-type
      lectin that mediates capture and internalization of viral, bacterial, and fungal
      pathogens by myeloid dendritic cells. DC-SIGN-interacting pathogens are thought
      to modulate dendritic cell maturation by interfering with intracellular signaling
      from Toll-like receptor molecules. We report that engagement of DC-SIGN by
      specific antibodies does not promote dendritic cell maturation but induces ERK1/2
      and Akt phosphorylation without concomitant p38MAPK activation. DC-SIGN ligation
      also triggers PLCgamma phosphorylation and transient increases in intracellular
      calcium in dendritic cells. In agreement with its signaling capabilities, a
      fraction of DC-SIGN molecules partitions within lipid raft-enriched membrane
      fractions both in DC-SIGN-transfected and dendritic cells. Moreover, DC-SIGN in
      dendritic cells coprecipitates with the tyrosine kinases Lyn and Syk. The
      relevance of the DC-SIGN-initiated signals was demonstrated in monocyte-derived
      dendritic cells, as DC-SIGN cross-linking synergizes with TNF-alpha for IL-10
      release and enhances the production of LPS-induced IL-10. These results
      demonstrate that DC-SIGN-triggered intracellular signals modulate dendritic cell
      maturation. Since pathogens stimulate Th2 responses via preferential activation
      of ERK1/2, these results provide a molecular explanation for the ability of DC
      SIGN-interacting pathogens to preferentially evoke Th2-type immune responses.

PMID- 16434486
TI  - Cellular prion protein is released on exosomes from activated platelets.
AB  - Cellular prion protein (PrP(C)) is a glycophosphatidylinositol (GPI)-anchored
      protein, of unknown function, found in a number of tissues throughout the body,
      including several blood components of which platelets constitute the largest
      reservoir in humans. It is widely believed that a misfolded, protease-resistant
      form of PrP(C), PrP(Sc), is responsible for the transmissible spongiform
      encephalopathy (TSE) group of fatal neurodegenerative diseases. Although the
      pathogenesis of TSEs is poorly understood, it is known that PrP(C) must be
      present in order for the disease to progress; thus, it is important to determine
      the physiologic function of PrP(C). Resolving the location of PrP(C) in blood
      will provide valuable clues as to its function. PrP(C) was previously shown to be
      on the alpha granule membrane of resting platelets. In the current study platelet
      activation led to the transient expression of PrP(C) on the platelet surface and
      its subsequent release on both microvesicles and exosomes. The presence of PrP(C)
      on platelet-derived exosomes suggests a possible mechanism for PrP(C) transport
      in blood and for cell-to-cell transmission.

PMID- 16434487
TI  - Circulating amyloidogenic free light chains and serum N-terminal natriuretic
      peptide type B decrease simultaneously in association with improvement of
      survival in AL.
AB  - N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac
      dysfunction in light chain amyloidosis (AL) and a powerful prognostic
      determinant. Serum NT-proBNP and circulating free light chains (FLCs) were
      measured at enrollment and after 3 cycles of chemotherapy in 51 patients with
      cardiac AL. In patients (n = 22, 43%) in whom FLCs decreased by more than 50%
      (hematologic response), NT-proBNP concentration decreased by a median of 48%,
      whereas in the remaining patients it increased by 47% (P = .01). The reduction of
      NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared
      at immunofixation (median 53%), than in the remaining responding patients (median
      31%, P = .04). Left ventricular wall thickness decreased by at least 2 mm in 3 of
      20 patients in whom NT-proBNP improved. Fifteen patients died. Thirteen of them,
      in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months.
      The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and
      improved survival. Patients in whom chemotherapy fails to induce such a decrease
      are at risk of early death. Cardiac function in AL can rapidly improve due to a
      reduction of the circulating amyloidogenic precursor, despite the amount of
      cardiac amyloid deposits remaining apparently unaltered, as measured by
      echocardiography.

PMID- 16434488
TI  - T-bet, a Th1 transcription factor, is up-regulated in T cells from patients with
      aplastic anemia.
AB  - In aplastic anemia, immune destruction of hematopoietic cells results in bone
      marrow failure. Type 1 cytokines, especially IFN-gamma, have been implicated in
      the pathophysiology of T-cell-mediated, Fas-mediated stem cell apoptosis of
      hematopoietic cells. Here, we show that the transcription factor T-bet (T-box
      expressed in T cells) is increased in T cells from patients with aplastic anemia.
      Patients' T-bet bound directly to the proximal site of the IFN-gamma promoter
      without any prior stimulation, in contrast to healthy controls. Increased levels
      of Itk kinase participated in T-bet up-regulation and active transcription of the
      IFN-gamma gene observed in these patients. Blocking PKC-, a kinase that lies
      downstream of Itk kinase, decreased T-bet protein and IFN-gamma intracellular
      levels. These data suggest that the increased IFN-gamma levels observed in
      aplastic anemia patients are the result of active transcription of the IFN-gamma
      gene by T-bet. Blocking the transcription of the IFN-gamma gene with kinase
      inhibitors might lead to the development of novel therapeutic agents for patients
      with aplastic anemia and other autoimmune diseases.

PMID- 16434489
TI  - Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating
      mutation that triggers neoplastic growth in most patients with systemic
      mastocytosis.
AB  - Mastocytosis is associated with an activating mutation in the KIT oncoprotein
      (KITD816V) that results in autophosphorylation of the KIT receptor in a ligand
      independent manner. This mutation is inherently resistant to imatinib and, to
      date, there remains no effective curative therapy for systemic mastocytosis
      associated with KITD816V. Dasatinib (BMS-354825) is a novel orally bioavailable
      SRC/ABL inhibitor that has activity against multiple imatinib-resistant BCR-ABL
      isoforms in vitro that is presently showing considerable promise in early-phase
      clinical trials of chronic myeloid leukemia (CML). Pharmacokinetic analysis
      suggests that high nanomolar concentrations of dasatinib can be achieved safely
      in humans. In this study, we demonstrate significant inhibitory activity of
      dasatinib against both wild-type KIT and the KITD816V mutation in the nanomolar
      range in in vitro and cell-based kinase assays. Additionally, dasatinib leads to
      growth inhibition of a KITD816V-harboring human masto-cytosis cell line.
      Significantly, dasatinib selectively kills primary neoplastic bone marrow mast
      cells from patients with systemic mastocytosis while sparing other hematopoietic
      cells. Computer modeling suggests that the KITD816V mutation destabilizes the
      inactive conformation of the KIT activation loop to which imatinib binds, but it
      is not predicted to impair binding of KIT by dasatinib. Based upon our results,
      further evaluation of dasatinib for the treatment of systemic masto-cytosis in
      clinical trials is warranted. Moreover, dasatinib may be of clinical utility in
      other disease settings driven by activating KIT mutations.

PMID- 16434490
TI  - X-inactivation-based clonality analysis and quantitative JAK2V617F assessment
      reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM,
      and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal
      hematopoiesis.
AB  - The JAK2V617F mutation is present in most patients with polycythemia vera (PV)
      and in some patients with essential thrombocythemia (ET) and myeloid
      metaplasia/myelofibrosis (MMM). We sought to investigate the relationship between
      granulocyte clonality and JAK2V617F allelic ratio. A total of 168 of 190 female
      patients were informative for a clonality assay at the HUMARA locus; 80% of MMM,
      75% of PV, and 67% of ET patients demonstrated clonal granulopoiesis. The
      JAK2V617F allele was detected by quantitative real-time polymerase chain reaction
      (PCR) in 99% of PV, 72% of ET, and 39% of MMM. A correlation between clonality
      and JAK2V617F allelic ratio was demonstrated for PV (P < .001) but not for ET or
      MMM (both P > .6). These data suggest that acquisition of the JAK2V617F mutation
      may be sufficient for the development of PV, but additional genetic events are
      necessary in ET and MMM. In addition, some ET and MMM patients with clonal
      granulopoiesis have somatic mutations other than JAK2V617F.

PMID- 16434491
TI  - A fibrinogen deficiency accelerates the initiation of LDL cholesterol-driven
      atherosclerosis via thrombin generation and platelet activation in genetically
      predisposed mice.
AB  - Mice with combined deficiencies of the low-density lipoprotein receptor (LDLR(-/
      )) and the catalytic component of an apolipoprotein B-edisome complex (APOBEC1(-/
      )) that converts apoB-100 to apoB-48 have been characterized, and this model of
      LDL cholesterol-driven atherosclerosis was applied to an investigation of the
      role of fibrinogen (Fg) in the genesis and progression of the plaque. LDLR(-/
      )/APOBEC1(-/-)/FG(-/-) (L(-/-)/A(-/-)/FG(-/-)) triple-deficient mice presented
      more advanced plaque in their aortic trees and aortic sinuses at 24, 36, and 48
      weeks of age compared to L(-/-)/A(-/-) mice, a feature that may result from
      enhanced platelet activation in these former mice. This is supported by the
      presence of hypercoagulability, increased CD61 and CD62P on resting platelets,
      and higher plasma soluble P-selectin in L(-/-)/A(-/-)/FG(-/-) mice as compared to
      L(-/-)/A(-/-), FG(-/-), or wild-type mice. The elevated higher molecular weight
      forms of von Willebrand factor (VWF) in L(-/-)/A(-/-)/FG(-/-) mice, revealed by
      increased VWF collagen binding activity, perhaps resulting from down-regulation
      of its cleaving metalloproteinase, ADAMTS13, further indicates enhanced platelet
      activation. Thus, the earlier arterial plaque deposition in L(-/-)/A(-/-)/FG(-/-)
      mice appears to contain a contribution from enhanced levels of thrombin and
      activated platelets, a synergistic consequence of an Fg deficiency combined with
      a high LDL cholesterol concentration.

PMID- 16434492
TI  - Implications of NRAS mutations in AML: a study of 2502 patients.
AB  - We analyzed 2502 patients with acute myeloid leukemia at diagnosis for NRAS
      mutations around the hot spots at codons 12, 13, and 61 and correlated the
      results to cytomorphology, cytogenetics, other molecular markers, and prognostic
      relevance of these mutations. Two hundred fifty-seven (10.3%) of 2502 patients
      had NRAS mutations (NRAS(mut)). Most mutations (112 of 257; 43.6%) were found at
      codon 12, mostly resulting in changes from glycine to asparagine. The history of
      AML did not differ significantly in association with NRAS mutations. The
      subgroups with inv(16)/t(16;16) and inv(3)/t(3;3) showed a significantly higher
      frequency of NRAS(mut) (50 of 133, 37.6% [P < .001], and 11 of 41, 26.8% [P =
      .004], respectively) than the total cohort. In addition, in these 2 subgroups,
      mutations of codon 61 were significantly overrepresented (both P < .001). In
      contrast, NRAS mutations were significantly underrepresented in t(15;17) (2 of
      102; 2%; P = .005) in the subgroup with MLL/11q23 rearrangements (3 of 77; 3.9%;
      P = .061) and in the complex aberrant karyotype (4 of 258; 1.6%; P < .001).
      Overall, we did not find a significant prognostic impact of NRAS(mut) for overall
      survival, event-free survival, and disease-free survival. However, there was a
      trend to better survival in most subgroups, especially when other molecular
      markers (FLT3-LM, MLL-PTD, and NPM) were taken into account.

PMID- 16434493
TI  - Roles of protease-activated receptors in a mouse model of endotoxemia.
AB  - Endotoxemia is often associated with extreme inflammatory responses and
      disseminated intravascular coagulation. Protease-activated receptors (PARs)
      mediate cellular responses to coagulation proteases, including platelet
      activation and endothelial cell reactions predicted to promote inflammation.
      These observations suggested that PAR activation by coagulation proteases
      generated in the setting of endotoxemia might promote platelet activation,
      leukocyte-mediated endothelial injury, tissue damage, and death. Toward testing
      these hypotheses, we examined the effect of PAR deficiencies that ablate platelet
      and endothelial activation by coagulation proteases in a mouse endotoxemia model.
      Although coagulation was activated as measured by thrombin-antithrombin (TAT)
      production and antithrombin III (ATIII) depletion, Par1(-/-), Par2(-/-), Par4(-/
      ), Par2(-/-):Par4(-/-), and Par1(-/-):Par2(-/-) mice all failed to show improved
      survival or decreased cytokine responses after endotoxin challenge compared with
      wild type. Thus, our results fail to support a necessary role for PARs in linking
      coagulation to inflammation or death in this model. Interestingly, endotoxin
      induced thrombocytopenia was not diminished in Par4(-/-) mice. Thus, a mechanism
      independent of platelet activation by thrombin was sufficient to cause
      thrombocytopenia in our model. These results raise the possibility that decreases
      in platelet count in the setting of sepsis may not be caused by disseminated
      intravascular coagulation but instead report on a sometimes parallel but
      independent process.

PMID- 16434495
TI  - A sensitive high-throughput method to detect activating mutations of Jak2 in
      peripheral-blood samples.

PMID- 16434494
TI  - Characterization of the megakaryocyte demarcation membrane system and its role in
      thrombopoiesis.
AB  - To produce blood platelets, megakaryocytes elaborate proplatelets, accompanied by
      expansion of membrane surface area and dramatic cytoskeletal rearrangements. The
      invaginated demarcation membrane system (DMS), a hallmark of mature cells, has
      been proposed as the source of proplatelet membranes. By direct visualization of
      labeled DMS, we demonstrate that this is indeed the case. Late in megakaryocyte
      ontogeny, the DMS gets loaded with PI-4,5-P(2), a phospholipid that is confined
      to plasma membranes in other cells. Appearance of PI-4,5-P(2) in the DMS occurs
      in proximity to PI-5-P-4-kinase alpha (PIP4Kalpha), and short hairpin (sh) RNA
      mediated loss of PIP4Kalpha impairs both DMS development and expansion of
      megakaryocyte size. Thus, PI-4,5-P(2) is a marker and possibly essential
      component of internal membranes. PI-4,5-P(2) is known to promote actin
      polymerization by activating Rho-like GTPases and Wiskott-Aldrich syndrome (WASp)
      family proteins. Indeed, PI-4,5-P(2) in the megakaryocyte DMS associates with
      filamentous actin. Expression of a dominant-negative N-WASp fragment or
      pharmacologic inhibition of actin polymerization causes similar arrests in
      proplatelet formation, acting at a step beyond expansion of the DMS and cell
      mass. These observations collectively suggest a signaling pathway wherein PI-4,5
      P(2) might facilitate DMS development and local assembly of actin fibers in
      preparation for platelet biogenesis.

PMID- 16434496
TI  - KIR-incompatible hematopoietic-cell transplantation for poor prognosis infant
      acute lymphoblastic leukemia.

PMID- 16434497
TI  - Impact of LMP-1 expression on clinical outcome in age-defined subgroups of
      patients with classical Hodgkin lymphoma.

PMID- 16434498
TI  - Cytomegalovirus seroprevalence is not higher in patients with mycosis
      fungoides/Sezary syndrome.

PMID- 16434499
TI  - Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7.

PMID- 16434500
TI  - Inhibition of hepatocarcinogenesis by the deletion of the p50 subunit of NF
      kappaB in mice administered the peroxisome proliferator Wy-14,643.
AB  - Wy-14,643 (WY) is a hypolipidemic drug that induces hepatic peroxisome
      proliferation and tumors in rodents. We previously showed that peroxisome
      proliferators increase NF-kappaB DNA binding activity in rats, mice, and hepatoma
      cell lines, and that mice deficient in the p50 subunit of NF-kappaB had much
      lower cell proliferation in response to the peroxisome proliferator ciprofibrate.
      In this study we examined the promotion of hepatocarcinogenesis by WY in the p50
      knockout (-/-) mice. The p50 -/- and wild type mice were first administered
      diethylnitrosamine (DEN) as an initiating agent. Mice were then fed a control
      diet or a diet containing 0.05% WY for 38 weeks. Wild-type mice receiving DEN
      only developed a low incidence of tumors, and the majority of wild-type mice
      receiving both DEN and WY developed tumors. However, no tumors were seen in any
      of the p50 -/- mice. Cell proliferation and apoptosis were measured in
      hepatocytes by BrdU labeling and the TUNEL assay, respectively. Treatment with
      DEN + WY increased both cell proliferation and apoptosis in both the wild-type
      and p50 -/- mice; DEN treatment alone has no effect. In the DEN/WY-treated mice,
      cell proliferation and apoptosis were slightly lower in the p50 -/- mice than in
      the wild-type mice. These data demonstrate that NF-kappaB is involved in the
      promotion of hepatic tumors by the peroxisome proliferator WY; however, the
      difference in tumor incidence could not be attributed to alterations in either
      cell proliferation or apoptosis.

PMID- 16434501
TI  - Four-dimensional imaging and quantification of gene expression in early
      developing zebrafish (Danio rerio) embryos.
AB  - Four-dimensional (4D) imaging is a powerful tool for studying three-dimensional
      (3D) changes in an organism through time. Different imaging systems for obtaining
      3D data from in vivo specimens have been developed but usually involved large and
      expensive machines. We successfully used a simple inverted compound microscope
      and a commercially available program to study and quantify in vivo changes in
      sonic hedgehog (shh) expression during early development in a green fluorescence
      protein (GFP) transgenic zebrafish (Danio rerio) line. We applied the 4D system
      to study the effect of 100 microM cadmium exposure on shh expression. In control
      zebrafish embryos, shh:GFP expression was detected at about 9 h post
      fertilization (hpf) and increased steadily in the next 7 h, peaking at about 17
      hpf and decreasing in the following 4 h. In the same time period, different shh
      expression volumes were observed in cadmium-treated and control embryos. Embryos
      affected by cadmium-exposure demonstrated a down-regulation in shh expression.
      The number of GFP-expressing cells measured by flow cytometry decreased, and
      expression of neurogenin-1, a downstream target of the shh signaling pathway, was
      down-regulated, providing additional supporting data on the effects of cadmium on
      shh. In summary, we demonstrated the setup of a 4D imaging system and its
      application to the quantification of gene expression.

PMID- 16434502
TI  - Endothelial health and diversity in the kidney.

PMID- 16434503
TI  - Antiangiogenic therapy in diabetic nephropathy.

PMID- 16434504
TI  - Urinary albumin excretion as a predictor of the development of hypertension in
      the general population.
AB  - The hypothesis that high urinary albumin excretion (UAE; indicating mild renal
      damage) may precede development of hypertension was tested, and the relation
      among UAE, GFR, and development of hypertension was investigated. Data of 4635
      patients of a prospective cohort study who participated in an extensive screening
      in 1997 to 1998 and 2001 to 2003 at our outpatient unit and were normotensive at
      baseline were used. Hypertension was defined according to the Seventh Report of
      the Joint National Committee on Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure criteria, UAE was measured in two consecutive 24-h urine
      samples, and GFR was calculated with the modified Modification of Diet in Renal
      Disease formula. Mean follow-up was 4.3 yr. Baseline UAE was significantly
      associated with the risk for developing hypertension (odds ratio 2.29; 95%
      confidence interval 1.77 to 2.95 per 10-fold increase of UAE). This association
      was independent of potential confounders. An interaction between UAE and GFR was
      found (P = 0.030), indicating that with elevated UAE and lowered GFR, but still
      within the normal range, the risk for developing hypertension was highest. In
      conclusion, these findings support the hypothesis that mild renal damage may
      precede the development of hypertension.

PMID- 16434505
TI  - How many glomerular profiles must be measured to obtain reliable estimates of
      mean glomerular areas in human renal biopsies?
AB  - The objective of this study was to investigate the number of glomerular profiles
      that are required for accurate estimates of mean profile area in a renal biopsy
      series. Slides from 384 renal biopsies from one center were reviewed. They
      contained a median of seven glomerular profiles or of four profiles without
      sclerosis. Profile areas were measured using stereologic point counting. The
      "true individual mean" for each biopsy was calculated and the "true population
      mean" for groups of biopsies derived. Individual and population "random sample
      means" then were calculated from a random sampling of profiles in each biopsy and
      were compared with true means for the same biopsies. The effect on the true
      population means of the entire group of biopsies was also assessed, as the
      minimum number of glomerular profiles that were required for inclusion was
      changed. In a single biopsy, random sampling of > or =10 profiles without
      exclusions and of eight profiles or more without sclerosis reliably estimated the
      true mean areas. In a group of 30 biopsies, random sampling of five or more
      glomeruli per biopsy reliably estimated the true population mean. In the
      aggregate series, inclusion of all 384 biopsies produced the most robust true
      population mean; the reliability of the estimates decreased as the numbers of
      eligible biopsies diminished with increasing requisite minimum numbers of
      profiles per biopsy. We conclude that, while > or =10 profiles might be needed
      for reliable area estimates in a single biopsy, far fewer profiles per biopsy can
      suffice when groups of biopsies are studied. In analyses of groups of biopsies,
      all available biopsies should be used without consideration of the number of
      glomerular profiles in each. Stipulation of a specific minimum number of
      glomeruli in each biopsy for inclusion reduces the power of analyses because
      fewer biopsies are available for evaluation.

PMID- 16434506
TI  - Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer
      in adult renal transplantation.
AB  - Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to
      cyclosporine (CsA), has been shown to inhibit rather than promote cancers in
      experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525
      enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to
      have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to
      first skin and nonskin malignancies were compared between treatments using a
      survival analysis. Mean annualized rates of skin malignancy were calculated, and
      the relative risk was determined using a Poisson model. Malignancy-free survival
      rates for nonskin malignancies were compared using Kaplan-Meier estimates and the
      log-rank test. At 5 yr, the median time to a first skin carcinoma was delayed
      (491 versus 1126 d; log-rank test, P = 0.007), and the risk for an event was
      significantly lower with SRL-ST therapy (relative risk SRL-ST to SRL-CsA-ST
      0.346; 95% confidence interval 0.227 to 0.526; P < 0.001, intention-to-treat
      analysis). The relative risks for both basal and squamous cell carcinomas were
      significantly reduced. Kaplan-Meier estimates of nonskin cancer were 9.6 versus
      4.0% (SRL-CsA-ST versus SRL-ST; P = 0.032, intention-to-treat analysis). Nonskin
      cancers included those of the lung, larynx, oropharynx, kidney, gastrointestinal
      tract, prostate, breast, thyroid, and cervix as well as glioma, liposarcoma,
      astrocytoma, leukemia, lymphoma, and Kaposi's sarcoma. Patients who received SRL
      based, calcineurin inhibitor-free therapy after CsA withdrawal at month 3 had a
      reduced incidence of both skin and nonskin malignancies at 5 yr after renal
      transplantation compared with those who received SRL therapy combined with CsA.
      Longer follow-up and additional trials are needed to confirm these promising
      results.

PMID- 16434508
TI  - Nationwide quality improvement--how are we doing and what can we do?

PMID- 16434509
TI  - The production and directed differentiation of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are being rapidly produced from chromosomally
      euploid, aneuploid, and mutant human embryos that are available from in vitro
      fertilization clinics treating patients for infertility or preimplantation
      genetic diagnosis. These hESC lines are an important resource for functional
      genomics, drug screening, and, perhaps eventually, cell and gene therapy. The
      methods for deriving hESCs are well established and repeatable and are relatively
      successful with a ratio of 1:10 to 1:2 new hESC lines produced from 4- to 8-d-old
      morula and blastocysts and from isolated inner cell mass cell clusters of human
      blastocysts. The hESCs can be formed and maintained on human somatic cells in
      humanized serum-free culture conditions and for several passages in cell-free
      culture systems. The hESCs can be transfected with DNA constructs. Their gene
      expression profiles are being described and immunological characteristics
      determined. They may be grown indefinitely in vitro while maintaining their
      original karyotype and epigenetic status, but this needs to be confirmed from
      time to time in long-term cultures. hESCs spontaneously differentiate in the
      absence of the appropriate cell feeder layer, when overgrown in culture and when
      isolated from the ESC colony. All three major embryonic lineages are produced in
      differentiating flat attachment cultures and unattached embryoid bodies. Cell
      progenitors of interest can be identified by markers, expression of reporter
      genes, and characteristic morphology, and the cells thereafter enriched for
      progenitor types and further culture to more mature cell types. Directed
      differentiation systems are well developed for ectodermal pathways that result in
      neural and glial cells and the mesendodermal pathway for cardiac muscle cells and
      many other cell types including hematopoietic progenitors and endothelial cells.
      Directed differentiation into endoderm has been more difficult to achieve,
      perhaps because of the lack of markers of early progenitors in this lineage.
      There are reports of enriched cultures of keratinocytes, pigmented retinal
      epithelium, neural crest cells and motor neurons, hepatic progenitors, and cells
      that have some markers of gut tissue and pancreatic islet-like cells. The
      prospects for use of hESC derivatives in regenerative medicine are significant,
      and there is much optimism for their potential contributions to human
      regenerative medicine.

PMID- 16434510
TI  - The science behind 25 years of ovarian stimulation for in vitro fertilization.
AB  - To allow selection of embryos for transfer after in vitro fertilization, ovarian
      stimulation is usually carried out with exogenous gonadotropins. To compensate
      for changes induced by stimulation, GnRH analog cotreatment, oral contraceptive
      pretreatment, late follicular phase human chorionic gonadotropin, and luteal
      phase progesterone supplementation are usually added. These approaches render
      ovarian stimulation complex and costly. The stimulation of multiple follicular
      development disrupts the physiology of follicular development, with consequences
      for the oocyte, embryo, and endometrium. In recent years, recombinant
      gonadotropin preparations have become available, and novel stimulation protocols
      with less detrimental effects have been developed. In this article, the
      scientific background to current approaches to ovarian stimulation for in vitro
      fertilization is reviewed. After a brief discussion of the relevant aspect of
      ovarian physiology, the development, application, and consequences of ovarian
      stimulation strategies are reviewed in detail.

PMID- 16434511
TI  - Endocrine regulation of human fetal growth: the role of the mother, placenta, and
      fetus.
AB  - The environment in which the fetus develops is critical for its survival and long
      term health. The regulation of normal human fetal growth involves many
      multidirectional interactions between the mother, placenta, and fetus. The mother
      supplies nutrients and oxygen to the fetus via the placenta. The fetus influences
      the provision of maternal nutrients via the placental production of hormones that
      regulate maternal metabolism. The placenta is the site of exchange between mother
      and fetus and regulates fetal growth via the production and metabolism of growth
      regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast
      invasion in early pregnancy and increased uteroplacental blood flow ensure
      sufficient growth of the uterus, placenta, and fetus. The placenta may respond to
      fetal endocrine signals to increase transport of maternal nutrients by growth of
      the placenta, by activation of transport systems, and by production of placental
      hormones to influence maternal physiology and even behavior. There are
      consequences of poor fetal growth both in the short term and long term, in the
      form of increased mortality and morbidity. Endocrine regulation of fetal growth
      involves interactions between the mother, placenta, and fetus, and these effects
      may program long-term physiology.

PMID- 16434512
TI  - Somatotropic and gonadotropic axes linkages in infancy, childhood, and the
      puberty-adult transition.
AB  - Integrative neuroendocrine control of the gonadotropic and somatotropic axes in
      childhood, puberty, and young adulthood proceeds via multiple convergent and
      divergent pathways in the human and experimental animal. Emerging ensemble
      concepts are required to embody independent, parallel, and interacting mechanisms
      that subserve physiological adaptations and pathological disruption of
      reproduction and growth. Significant advances in systems biology will be needed
      to address these challenges.

PMID- 16434513
TI  - The evolution of functional bracing of fractures.

PMID- 16434515
TI  - The international rank order of publications in major clinical orthopaedic
      journals from 2000 to 2004.

PMID- 16434514
TI  - The management of peri-prosthetic infection in total joint arthroplasty.

PMID- 16434516
TI  - The impact factor of seven orthopaedic journals: factors influencing it.

PMID- 16434517
TI  - Imageless navigation for insertion of the acetabular component in total hip
      arthroplasty: is it as accurate as CT-based navigation?
AB  - In a prospective randomised clinical study acetabular components were implanted
      either freehand (n = 30) or using CT-based (n = 30) or imageless navigation (n =
      30). The position of the component was determined post-operatively on CT scans of
      the pelvis. Following conventional freehand placement of the acetabular
      component, only 14 of the 30 were within the safe zone as defined by Lewinnek et
      al (40 degrees inclination sd 10 degrees ; 15 degrees anteversion sd 10 degrees
      ). After computer-assisted navigation 25 of 30 acetabular components (CT-based)
      and 28 of 30 components (imageless) were positioned within this limit (overall p
      < 0.001). No significant differences were observed between CT-based and imageless
      navigation (p = 0.23); both showed a significant reduction in variation of the
      position of the acetabular component compared with conventional freehand
      arthroplasty (p < 0.001). The duration of the operation was increased by eight
      minutes with imageless and by 17 minutes with CT-based navigation. Imageless
      navigation proved as reliable as that using CT in positioning the acetabular
      component.

PMID- 16434518
TI  - The effect of fixation and location on the stability of the markers in navigated
      total hip arthroplasty: a cadaver study.
AB  - In navigated total hip arthroplasty, the pelvis and the femur are tracked by
      means of rigid bodies fixed directly to the bones. Exact tracking throughout the
      procedure requires that the connection between the marker and bone remains stable
      in terms of translation and rotation. We carried out a cadaver study to compare
      the intra-operative stability of markers consisting of an anchoring screw with a
      rotational stabiliser and of pairs of pins and wires of different diameters
      connected with clamps. These devices were tested at different locations in the
      femur. Three human cadavers were placed supine on an operating table, with a
      reference marker positioned in the area of the greater trochanter. K-wires (3.2
      mm), Steinman pins (3 and 4 mm), Apex pins (3 and 4 mm), and a standard screw
      were used as fixation devices. They were positioned medially in the proximal
      third of the femur, ventrally in the middle third and laterally in the distal
      portion. In six different positions of the leg, the spatial positions were
      recorded with a navigation system. Compared with the standard single screw, with
      the exception of the 3 mm Apex pins, the two-pin systems were associated with
      less movement of the marker and could be inserted less invasively. With the knee
      flexed to 90 degrees and the dislocated hip rotated externally until the lower
      leg was parallel to the table (figure-four position), all the anchoring devices
      showed substantial deflection of 1.5 degrees to 2.5 degrees . The most secure
      area for anchoring markers was the lateral aspect of the femur.

PMID- 16434519
TI  - Total hip replacement with a superolateral bone graft for osteoarthritis
      secondary to dysplasia: a long-term follow-up.
AB  - We evaluated the long-term results of 116 total hip replacements with a
      superolateral shelfplasty in 102 patients with osteoarthritis secondary to
      developmental dysplasia of the hip. After a mean follow-up of 19.5 years (11.5 to
      26.0), 14 acetabular components (12%) had been revised. The cumulative survival
      at 20 years was 78%, with revision for loosening of the acetabular component as
      the end-point. All grafts were well integrated and showed remodelling. In six
      grafts some resorption had occurred under the heads of the screws where the graft
      was not supporting the socket. Apart from these 14 revisions, seven acetabular
      components had possible radiological signs of loosening at a mean follow-up of
      14.5 years, one had signs of probable loosening, and five had signs of definite
      loosening. These results indicate that this technique of bone grafting for
      acetabular reconstruction in hip dysplasia is a durable solution for cemented
      acetabular components.

PMID- 16434520
TI  - The premature failure of the Charnley Elite-Plus stem: a confirmation of RSA
      predictions.
AB  - We performed a clinical and radiological study to determine the rate of failure
      of the Charnley Elite-Plus femoral component. Our aim was to confirm or refute
      the predictions of a previous roentgen stereophotogrammetric analysis study in
      which 20% of the Charnley Elite-Plus stems had shown rapid posterior head
      migration. It was predicted that this device would have a high early rate of
      failure.We examined 118 patients at a mean of nine years after hip replacement,
      including the 19 patients from the original roentgen stereophotogrammetric study.
      The number of revision procedures was recorded and clinical and radiological
      examinations were performed. The rate of survival of the femoral stems at ten
      years was 83% when revision alone was considered to be a failure. It decreased to
      59% when a radiologically loose stem was also considered to be a failure. All the
      patients previously shown in the roentgen stereophotogrammetric study to have
      high posterior head migration went on to failure. There was a highly significant
      difference (p = 0.002) in posterior head migration measured at two years after
      operation between failed and non-failed femoral stems, but there was no
      significant difference in subsidence between these two groups. Our study has
      shown that the Charnley Elite-Plus femoral component has an unacceptably high
      rate of failure. It confirms that early evaluation of new components is important
      and that roentgen stereophotogrammetric is a good tool for this. Our findings
      have also shown that rapid posterior head migration is predictive of premature
      loosening and a better predictor than subsidence.

PMID- 16434521
TI  - The angle-bore acetabular component and dislocation after revision of a failed
      total hip replacement.
AB  - We reviewed 1039 revision total hip replacements where an angle-bore acetabular
      component was used. After a mean follow-up of nine years (0 to 20.6), the
      incidence of revision for dislocation was 2.1% (22 revisions), a success rate of
      97.9%. In 974 revisions, where the indication was other than dislocation, the
      success rate was 98.5%. Of the 65 revisions for dislocation, 58 (89.2%) were
      successful after the first revision and a further five after the second revision,
      an overall success of 96.9%. Two patients elected to have their implants removed.
      Dislocation after revision of failed total hip replacement is a complex issue.
      There is often no single cause and no simple solution. The angle-bore acetabular
      component, in combination with a 22.225-mm diameter femoral head, offers a high
      level of success.

PMID- 16434522
TI  - Hands-on robotic unicompartmental knee replacement: a prospective, randomised
      controlled study of the acrobot system.
AB  - We performed a prospective, randomised controlled trial of unicompartmental knee
      arthroplasty comparing the performance of the Acrobot system with conventional
      surgery. A total of 27 patients (28 knees) awaiting unicompartmental knee
      arthroplasty were randomly allocated to have the operation performed
      conventionally or with the assistance of the Acrobot. The primary outcome
      measurement was the angle of tibiofemoral alignment in the coronal plane,
      measured by CT. Other secondary parameters were evaluated and are reported. All
      of the Acrobot group had tibiofemoral alignment in the coronal plane within 2
      degrees of the planned position, while only 40% of the conventional group
      achieved this level of accuracy. While the operations took longer, no adverse
      effects were noted, and there was a trend towards improvement in performance with
      increasing accuracy based on the Western Ontario and McMaster Universities
      Osteoarthritis Index and American Knee Society scores at six weeks and three
      months. The Acrobot device allows the surgeon to reproduce a pre-operative plan
      more reliably than is possible using conventional techniques which may have
      clinical advantages.

PMID- 16434523
TI  - Are systemic emboli reduced in computer-assisted knee surgery?: A prospective,
      randomised, clinical trial.
AB  - We undertook a prospective, randomised study using a non-invasive transcranial
      Doppler device to evaluate cranial embolisation in computer-assisted navigated
      total knee arthroplasty (n = 14) and compared this with a standard conventional
      surgical technique using intramedullary alignment guides (n = 10). All patients
      were selected randomly without the knowledge of the patient, anaesthetists
      (before the onset of the procedure) and ward staff. The operations were performed
      by a single surgeon at one hospital using a uniform surgical approach,
      instrumentation, technique and release sequence. The only variable in the two
      groups of patients was the use of single tracker pins of the imageless navigation
      system in the tibia and femur of the navigated group and intramedullary femoral
      and tibial alignment jigs in the non-navigated group. Acetabular Doppler signals
      were obtained in 14 patients in the computer-assisted group and nine (90%) in the
      conventional group, in whom high-intensity signals were detected in seven
      computer-assisted patients (50%) and in all of the non-navigated patients. In the
      computer-assisted group no patient had more than two detectable emboli, with a
      mean of 0.64 (SD 0.74). In the non-navigated group the number of emboli ranged
      from one to 43 and six patients had more than two detectable emboli, with a mean
      of 10.7 (sd 13.5). The difference between the two groups was highly significant
      using the Wilcoxon non-parametric test (p = 0.0003).Our findings show that
      computer-assisted total knee arthroplasty, when compared with conventional jig
      based surgery, significantly reduces systemic emboli as detected by transcranial
      Doppler ultrasonography.

PMID- 16434524
TI  - Collagen-covered autologous chondrocyte implantation for osteochondritis
      dissecans of the knee: two- to seven-year results.
AB  - We prospectively studied the clinical, arthroscopic and histological results of
      collagen-covered autologous chondrocyte implantation (ACI-C) in patients with
      symptomatic osteochondritis dissecans of the knee. The study included 37 patients
      who were evaluated at a mean follow-up of 4.08 years. Clinical results showed a
      mean improvement in the modified Cincinnati score from 46.1 to 68.4. Excellent
      and good clinical results were seen in 82.1% of those with juvenile-onset
      osteochondritis dissecans but in only 44.4% of those with adult-onset disease.
      Arthroscopy at one year revealed International Cartilage Repair Society grades of
      1 or 2 in 21 of 24 patients (87.5%). Of 23 biopsies, 11 (47.8%) showed either a
      hyaline-like or a mixture of hyaline-like and fibrocartilage, 12 (52.2%) showed
      fibrocartilage. The age at the time of ACI-C determined the clinical outcome for
      juvenile-onset disease (p = 0.05), whereas the size of the defect was the major
      determinant of outcome in adult-onset disease (p = 0.01).

PMID- 16434525
TI  - Ankle arthrodesis and its relationship to ipsilateral arthritis of the hind- and
      mid-foot.
AB  - It has been suggested that arthrodesis of the ankle leads to osteoarthritis of
      the joints of the ipsilateral hind- and midfoot. We believe these studies
      overlooked the presence of osteoarthritic changes in these joints before the
      arthrodesis. We reviewed the pre-operative radiographs of 70 patients with
      osteoarthritis of the ankle who underwent 71 ankle arthrodeses (one was
      bilateral). The talonavicular, calcaneocuboid, subtalar and naviculocuneiform
      joints were given an osteoarthritis score according to Kellgren and Lawrence. The
      mean age at operation was 54.9 years and the most common indication was for post
      traumatic osteoarthritis (52 cases). A total of 68 patients showed pre-existing
      arthritis in either the hind- or mid-foot, with the subtalar joint the most
      commonly affected. Ipsilateral hind- and mid-foot arthritis is almost universally
      present in patients with arthritis of the ankle requiring arthrodesis. The
      presence of such changes may not be a consequence of this arthrodesis.

PMID- 16434526
TI  - Transfer of the tendon of latissimus dorsi for the treatment of massive tears of
      the rotator cuff: a new single-incision technique.
AB  - We describe 14 patients who underwent transfer of latissimus dorsi using a new
      technique through a single-incision. Their mean age was 61 years (47 to 76) and
      the mean follow-up was 32 months (19 to 42). The mean Constant score improved
      from 46.5 to 74.6 points. The mean active flexion increased from 119 degrees to
      170 degrees , mean abduction from 118 degrees to 169 degrees and mean external
      rotation from 19 degrees to 33 degrees . The Hornblower sign remained positive in
      three patients (23%) as did the external rotation lag sign also in three patients
      (23%). No patient had a positive drop-arm sign at follow-up. No significant
      difference was noted between the mean pre- and postoperative acromiohumeral
      distance as seen on radiographs. An increased grade of osteoarthritis was found
      in three patients (23%). Electromyographic analysis showed activity of the
      transferred muscle in all patients.

PMID- 16434527
TI  - Posterior subluxation and dislocation of the shoulder in obstetric brachial
      plexus palsy.
AB  - We describe the results of surgical treatment in a prospective study of 183
      consecutive cases of subluxation (101) and dislocation (82) of the shoulder
      secondary to obstetric brachial plexus palsy between 1995 and 2000. Neurological
      recovery was rated 'good' or 'useful' in all children, whose lesions fell into
      groups 1, 2 or 3 of the Narakas classification. The mean age at operation was 47
      months (3 to 204). The mean follow-up was 40 months (24 to 124). The mean gain in
      function was 3.6 levels (9.4 to 13) using the Mallet score and 2 (2.1 to 4.1) on
      the Gilbert score. The mean active global range of shoulder movement was
      increased by 73 degrees ; the mean range of active lateral rotation by 58 degrees
      and that of supination of the forearm by 51 degrees . Active medial rotation was
      decreased by a mean of 10 degrees . There were 20 failures. The functional
      outcome is related to the severity of the neurological lesion, the duration of
      the dislocation and onset of deformity.

PMID- 16434528
TI  - Subperiosteal elevation of the ulnar nerve during internal fixation for fractures
      of the distal humerus assessed by intra-operative neurophysiological monitoring.
AB  - Ulnar nerve function, during and after open reduction and internal fixation of
      fractures of the distal humerus with subperiosteal elevation of the nerve, was
      assessed by intra-operative neurophysiological monitoring. Intermittent recording
      of the compound muscle action potentials was taken from the hypothenar muscles in
      18 neurologically asymptomatic patients. The mean amplitude of the compound
      muscle action potential after surgery was 98.1% (sd 17.6; -37% to +25%). The
      amplitude improved in six patients following surgery. Despite unremarkable
      recordings one patient had progressive paresis. Motor impairment is unlikely if
      the compound muscle action potential is continuously preserved and not reduced by
      more than 40% at the end of surgery. Temporary decreases in amplitude by up to
      70% were tolerated without clinical consequences. However, repeated clinical
      examination is obligatory to recognise and treat early post-operative palsy.

PMID- 16434529
TI  - Factors affecting fracture healing after intramedullary nailing of the tibial
      diaphysis for closed and grade I open fractures.
AB  - As there is little information on the factors that influence fracture union
      following intramedullary nailing of the tibia we retrospectively investigated
      patient-, injury- and treatment-related factors in 161 patients with closed or
      grade I open fractures of the tibial diaphysis. The patients were reviewed until
      clinical and radiological evidence of union at a mean of 13.3 months (4 to 60).
      Multivariate statistical analysis using a Cox proportional hazards model showed
      that the risk of failure of union increased by 2.38 times for highly comminuted
      fractures, by 3.14 times when nail dynamisation was applied, and by 1.65 times
      when the locking screws failed. In fractures with no or only minimal comminution
      the risk of nonunion increased if the post-reduction gap was > or = 3 mm.

PMID- 16434530
TI  - The use of the Ilizarov method as a salvage procedure in infected nonunion of the
      distal femur with bone loss.
AB  - We reviewed 13 patients with infected nonunion of the distal femur and bone loss,
      who had been treated by radical surgical debridement and the application of an
      Ilizarov external fixator. All had severely restricted movement of the knee and a
      mean of 3.1 previous operations. The mean length of the bony defect was 8.3 cm
      and no patient was able to bear weight. The mean external fixation time was 309.8
      days. According to Paley's grading system, eight patients had an excellent
      clinical and radiological result and seven excellent and good functional results.
      Bony union, the ability to bear weight fully, and resolution of the infection
      were achieved in all the patients. The external fixation time was increased when
      the definitive treatment started six months or more after the initial trauma, the
      patient had been subjected to more than four previous operations and the initial
      operation had been open reduction and internal fixation.

PMID- 16434531
TI  - A comparison of three methods of wound closure following arthroplasty: a
      prospective, randomised, controlled trial.
AB  - We carried out a blinded prospective randomised controlled trial comparing 2
      octylcyanoacrylate (OCA), subcuticular suture (monocryl) and skin staples for
      skin closure following total hip and total knee arthroplasty. We included 102 hip
      replacements and 85 of the knee.OCA was associated with less wound discharge in
      the first 24 hours for both the hip and the knee. However, with total knee
      replacement there was a trend for a more prolonged wound discharge with OCA. With
      total hip replacement there was no significant difference between the groups for
      either early or late complications. Closure of the wound with skin staples was
      significantly faster than with OCA or suture. There was no significant difference
      in the length of stay in hospital, Hollander wound evaluation score (cosmesis) or
      patient satisfaction between the groups at six weeks for either hips or knees. We
      consider that skin staples are the skin closure of choice for both hip and knee
      replacements.

PMID- 16434532
TI  - Morphometric analysis of acetabular dysplasia in cerebral palsy.
AB  - We carried out a morphometric analysis of acetabular dysplasia in patients with
      cerebral palsy requiring hip surgery using three-dimensional CT. We evaluated 54
      hips in 27 patients. The contralateral normal hips of ten patients with
      unilateral Perthes' disease were used as a control group. The acetabular defects
      were assessed qualitatively as anterior, posterior or global. Quantitative
      assessments were made using three-directional acetabular indices (anterosuperior,
      superolateral and posterosuperior) and measured by multiplanar reformation, from
      which we calculated the acetabular volume. In the qualitative study, posterior
      defects were most common in the subluxation group whereas global defects
      predominated in the dislocation group. In the quantitative study, all acetabular
      indices in both the subluxation and dislocation groups were higher than those in
      the control group and the superolateral indices showed a tendency to elevation in
      the dislocation group. The acetabular volume was largest in the control group,
      smallest in the dislocation group, and intermediate between the two in the
      subluxation group.

PMID- 16434533
TI  - Lengthening and transfer of hamstrings for a flexion deformity of the knee in
      children with bilateral cerebral palsy: technique and preliminary results.
AB  - Between July 2000 and April 2004, 19 patients with bilateral spastic cerebral
      palsy who required an assistive device to walk had combined lengthening-transfer
      of the medial hamstrings as part of multilevel surgery. A standardised physical
      examination, measurement of the Functional Mobility Scale score and video or
      instrumented gait analysis were performed pre- and post-operatively. Static
      parameters (popliteal angle, flexion deformity of the knee) and sagittal knee
      kinematic parameters (knee flexion at initial contact, minimum knee flexion
      during stance, mean knee flexion during stance) were recorded. The mean length of
      follow-up was 25 months (14 to 45). Statistically significant improvements in
      static and dynamic outcome parameters were found, corresponding to improvements
      in gait and functional mobility as determined by the Functional Mobility Scale.
      Mild hyperextension of the knee during gait developed in two patients and was
      controlled by adjustment of their ankle-foot orthosis. Residual flexion deformity
      > 10 degrees occurred in both knees of one patient and was treated by anterior
      distal femoral physeal stapling. Two children also showed an improvement of one
      level in the Gross Motor Function Classification System.

PMID- 16434534
TI  - Treatment of multiple hereditary osteochondromas of the forearm in children: a
      study of surgical procedures.
AB  - We have evaluated the clinical outcomes of simple excision, ulnar lengthening and
      the Sauve-Kapandji procedure in the treatment of deformities of the forearm in
      patients with multiple hereditary osteochondromas. The medical records of 29
      patients (33 forearms) were reviewed; 22 patients (22 forearms) underwent simple
      excision (four with ulnar lengthening) and seven the Sauve-Kapandji procedure.
      Simple excision increased the mean supination of the forearm from 63.2 degrees to
      75.0 degrees (p = 0.049). Ulnar lengthening did not significantly affect the
      clinical outcome. The Sauve-Kapandji technique improved the mean pronation from
      33.6 degrees to 55.0 degrees (p = 0.047) and supination from 70.0 degrees to 81.4
      degrees (p = 0.045). Simple excision may improve the range of movement of the
      forearm but will not halt the progression of disease, particularly in younger
      patients. No discernable clinical or radiological improvement was noted with
      ulnar lengthening. The Sauve-Kapandji procedure combined with simple excision of
      osteochondromas can improve stability of the wrist, movement of the forearm and
      the radiological appearance.

PMID- 16434535
TI  - Lemierre's syndrome: an unusual manifestation of spinal infection.
AB  - We report a case of Lemierre's syndrome complicated by an epidural abscess. This
      manifestation of Lemierre's syndrome has not been described previously.

PMID- 16434536
TI  - The use of immunomodulators as an adjunct to antituberculous chemotherapy in non
      responsive patients with osteo-articular tuberculosis.
AB  - We studied 51 patients with osteo-articular tuberculosis who were divided into
      two groups. Group I comprised 31 newly-diagnosed patients who were given first
      line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol
      and pyrazinamide. Group II (non-responders) consisted of 20 patients with a
      history of clinical non-responsiveness to supervised uninterrupted
      antituberculous treatment for a minimum of three months or a recurrence of a
      previous lesion which on clinical observation had healed. No patient in either
      group was HIV-positive. Group II were treated with an immunomodulation regime of
      intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus
      vaccines as an adjunct for eight weeks in addition to antituberculous treatment.
      We gave antituberculous treatment for a total of 12 to 18 months in both groups
      and they were followed up for a mean of 30.2 months (24 to 49). A series of 20
      healthy blood donors served as a control group.Twenty-nine (93.6%) of the 31
      patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological
      healing response to treatment by five months. The CD4 cell count in both groups
      was depressed at the time of enrolment, with a greater degree of depression in
      the group-II patients (686 cells/mm(3) (sd 261) and 545 cells/mm(3) (sd 137),
      respectively; p < 0.05). After treatment for three months both groups showed
      significant elevation of the CD4 cell count, reaching a level comparable with the
      control group. However, the mean CD4 cell count of group II (945 cells/mm(3) (sd
      343)) still remained lower than that of group I (1071 cells/mm(3) (sd 290)), but
      the difference was not significant. Our study has shown encouraging results after
      immunomodulation and antituberculous treatment in non-responsive patients. The
      pattern of change in the CD4 cell count in response to treatment may be a
      reliable clinical indicator.

PMID- 16434537
TI  - The preparation of ciprofloxacin hydrochloride-loaded chitosan and pectin
      microspheres: their evaluation in an animal osteomyelitis model.
AB  - Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying
      method using pectin and chitosan. The effects of different polymers and drug
      ratios were investigated. The most appropriate carriers were selected by in vitro
      testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model
      was used to evaluate the effects of the loaded microspheres. The drug was
      released rapidly from the pectin carrier but this was more sustained in the
      chitosan formulation.Chitosan microspheres loaded with ciprofloxacin
      hydrochloride were more effective for the treatment of osteomyelitis than
      equivalent intramuscular antibiotics.

PMID- 16434538
TI  - A completely shattered tibia.

PMID- 16434539
TI  - Modern concepts in the treatment of hallux valgus.

PMID- 16434540
TI  - Modern concepts in the treatment of hallux valgus.

PMID- 16434541
TI  - Venous thromboembolism associated with hip and knee replacement over a ten-year
      period.

PMID- 16434542
TI  - Linkage analysis of neointimal hyperplasia and vascular wall transformation after
      balloon angioplasty.
AB  - Neointimal hyperplasia (NIH), a result of vascular injury, is due to the
      migration and proliferation of smooth muscle cells through the media and internal
      elastic lamina leading to vascular occlusion. We used a rat model to find the
      genetic regions controlling NIH after endothelial denudation in two divergent
      inbred strains of rats. The Brown Norway (BN) and spontaneously hypertensive rat
      (SHR) strains have a 2.5-fold difference in injury-induced NIH. A population of
      301 F2 (SHR x BN) rats underwent a standard vascular injury followed by
      phenotyping 8 wk after injury to identify quantitative trait loci (QTL)
      responsible for this strain difference. Interval mapping identified two %NIH QTL
      on rat chromosomes 3 and 6 [logarithm of odds (LOD) scores 2.5, 2.2] and QTL for
      other injured vascular wall changes on rat chromosomes 3, 4, and 15 (LOD scores
      2.0-4.6). Also, QTL for control vessel media width (MW) and media area (MA) were
      found on chromosome 6 with LOD scores of 2.3 and 2.5, suggesting that linkage
      exists between these control vessel parameters and NIH production. These results
      represent the first genetic analysis for the identification of NIH QTL and QTL
      associated with the vascular injury response.

PMID- 16434543
TI  - Cholesterol-metabolizing cytochromes P450.
AB  - By catalyzing the first steps in different pathways of cholesterol degradation,
      cytochromes P450 (P450s) 7A1, 27A1, 11A1, and 46A1 play key roles in cholesterol
      homeostasis. CYP7A1 is a microsomal liver-specific enzyme that converts
      cholesterol to 7alpha-hydroxycholesterol. CYP27A1 is a ubiquitously expressed
      mitochondrial P450 that metabolizes cholesterol to 27-hydroxycholesterol. CYP11A1
      also resides in mitochondria but is expressed mainly in steroidogenic tissues,
      where it catalyzes the conversion of cholesterol to pregnenolone. Finally,
      CYP46A1 is a brain-selective microsomal monooxygenase producing 24S
      hydroxycholesterol from cholesterol. Catalytic efficiencies of cholesterol
      metabolizing P450s vary significantly and probably reflect physiological
      requirements of different organs for the rate of cholesterol turnover. P450s 7A1,
      27A1, 11A1, and 46A1 represent a unique system for elucidation of how different
      enzymes have adapted to fit their specific roles in cholesterol elimination.
      Studies of cholesterol-metabolizing P450s suggest that their activities could be
      modulated post-translationally and that they should also be considered as targets
      for regulation of cholesterol homeostasis.

PMID- 16434544
TI  - Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone
      antibiotics and affects their oral availability, pharmacokinetics, and milk
      secretion.
AB  - The breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette drug
      efflux transporter that extrudes xenotoxins from cells in intestine, liver,
      mammary gland, and other organs, affecting the pharmacological and toxicological
      behavior of many compounds, including their secretion into the milk. The purpose
      of this study was to determine whether three widely used fluoroquinolone
      antibiotics (ciprofloxacin, ofloxacin, and norfloxacin) are substrates of
      Bcrp1/BCRP and to investigate the possible role of this transporter in the in
      vivo pharmacokinetic profile of these compounds and their secretion into the
      milk. Using polarized cell lines, we found that ciprofloxacin, ofloxacin, and
      norfloxacin are transported by mouse Bcrp1 and human BCRP. In vivo
      pharmacokinetic studies showed that the ciprofloxacin plasma concentration was
      more than 2-fold increased in Bcrp1(-/-) compared with wild-type mice (1.77 +/-
      0.73 versus 0.85 +/- 0.39 microg/ml, p < 0.01) after oral administration of
      ciprofloxacin (10 mg/kg). The area under the plasma concentration-time curve in
      Bcrp1(-/-) mice was 1.5-fold higher than that in wild-type mice (48.63 +/- 5.66
      versus 33.10 +/- 4.68 min x microg/ml, p < 0.05) after i.v. administration (10
      mg/kg). The milk concentration and milk/plasma ratio of ciprofloxacin were 2-fold
      higher in wild-type than in Bcrp1(-/-) lactating mice. We conclude that Bcrp1 is
      one of the determinants for the bioavailability of fluoroquinolones and their
      secretion into the milk.

PMID- 16434545
TI  - Altered hepatobiliary disposition of 5 (and 6)-carboxy-2',7'-dichlorofluorescein
      in Abcg2 (Bcrp1) and Abcc2 (Mrp2) knockout mice.
AB  - This study characterized the hepatobiliary disposition of 5 (and 6)-carboxy-2',7'
      dichlorofluorescein (CDF), a model Abcc2/Mrp2 (canalicular) and Abcc3/Mrp3
      (basolateral) substrate, in perfused livers from male C57BL/6 wild-type, Abcg2-/
      , and Abcc2-/- mice. After single-pass liver perfusion with 1 muM CDF diacetate
      for 30 min and an additional 30-min perfusion with CDF-free buffer, cumulative
      biliary excretion of CDF in Abcg2-/- mice was significantly higher than in wild
      type mice (65 +/- 6 and 47 +/- 15% of dose, respectively, p < 0.05), whereas CDF
      recovery in bile of Abcc2-/- mice was negligible. Cumulative recovery of CDF in
      perfusate was significantly higher in Abcc2-/- (90 +/- 8% of dose) relative to
      wild-type (35 +/- 11% of dose) mice. Compartmental pharmacokinetic analysis
      revealed that the rate constant for CDF biliary excretion was significantly
      increased in Abcg2-/- (0.061 +/- 0.005 min(-1)) compared with wild-type (0.039 +/
      0.011 min(-1)) mice. The rate constant governing the basolateral excretion of
      CDF was approximately 4-fold higher in Abcc2-/- (0.12 +/- 0.02 min(-1)) relative
      to wild-type (0.030 +/- 0.011 min(-1)) mice but was not altered in Abcg2-/-
      (0.031 +/- 0.004 min(-1)) mice. Hepatic Abcc3 protein levels, determined by
      immunoblot analysis, were approximately 60% higher in Abcc2-/- mice than in wild
      type mice. In contrast, neither Abcc3 protein levels nor Abcc2 mRNA levels were
      altered in Abcg2-/- relative to wild-type mice. These data in knockout mouse
      models demonstrate that loss of expression and function of one canalicular
      transport protein may change the route and/or extent of excretion into bile or
      perfusate because of alterations in the function of other basolateral or
      canalicular transport proteins.

PMID- 16434546
TI  - Dependence of nelfinavir brain uptake on dose and tissue concentrations of the
      selective P-glycoprotein inhibitor zosuquidar in rats.
AB  - Most reverse transcriptase and protease inhibitors used in highly active
      antiretroviral therapy for treating human immunodeficiency virus (HIV) infections
      exhibit poor penetration into the brain, raising the concern that the brain may
      be a sanctuary site for the development of resistant HIV variants. This study
      explores the relationship between the dose and plasma and brain concentrations of
      zosuquidar and the effect of this selective P-glycoprotein inhibitor on central
      nervous system penetration of the HIV protease inhibitor nelfinavir maintained at
      steady state by intravenous infusions in rats. Nelfinavir was infused (10
      mg/kg/h) for up to 10 h with or without concurrent administration of an
      intravenous bolus dose of 2, 6, or 20 mg/kg zosuquidar given at 4 h. Brain tissue
      and plasma were analyzed for both drug concentrations. Brain tissue/plasma
      nelfinavir concentration ratios (uncorrected for the vascular contribution)
      increased nonlinearly with zosuquidar dose from 0.06 +/- 0.03 in the absence of
      zosuquidar and 0.09 +/- 0.02 between 2 and 6 h after 2 mg/kg zosuquidar to 0.85
      +/- 0.19 after 6 mg/kg and 1.58 +/- 0.67 after 20 mg/kg zosuquidar. Zosuquidar
      brain tissue/plasma concentration ratios exhibited a similar abrupt increase from
      2.8 +/- 0.3 after a 2 mg/kg dose to approximately 15 after the 6 and 20 mg/kg
      doses. The apparent threshold in the plasma concentration of zosuquidar necessary
      to produce significant enhancement in brain uptake of nelfinavir appears to be
      close to the plasma concentrations associated with the maximum tolerated dose
      reported in the literature after repeated dosing of zosuquidar in patients.

PMID- 16434547
TI  - In vitro metabolic activation of thiabendazole via 5-hydroxythiabendazole:
      identification of a glutathione conjugate of 5-hydroxythiabendazole.
AB  - Thiabendazole (TBZ) is a broad-spectrum antihelmintic used for treatment of
      parasitic infections in animals and humans and as an agricultural fungicide for
      postharvest treatment of fruits and vegetables. It is teratogenic and nephrotoxic
      in mice, and cases of hepatotoxicity have been observed in humans. Recent reports
      have demonstrated a correlation between 5-hydroxythiabendazole (5-OHTBZ)
      formation, a major metabolite of TBZ, and covalent binding of [(14)C]TBZ to
      hepatocytes, suggesting another pathway of activation of TBZ. Current in vitro
      studies were undertaken to probe the bioactivation of TBZ via 5-OHTBZ by
      cytochrome P450 (P450) and peroxidases and identify the reactive species by
      trapping with reduced glutathione (GSH). Microsomal incubation of TBZ or 5-OHTBZ
      supplemented with NADPH and GSH afforded a GSH adduct of 5-OHTBZ and was
      consistent with a bioactivation pathway that involved a P450-catalyzed two
      electron oxidation of 5-OHTBZ to a quinone imine. The same adduct was detected in
      GSH-fortified incubations of 5-OHTBZ with peroxidases. The identity of the GSH
      conjugate suggested that the same reactive intermediate was formed by both these
      enzyme systems. Characterization of the conjugate by mass spectrometry and NMR
      revealed the addition of GSH at the 4-position of 5-OHTBZ. In addition, the
      formation of a dimer of 5-OHTBZ was discernible in peroxidase-mediated
      incubations. These results were consistent with a one-electron oxidation of 5
      OHTBZ to a radical species that could undergo disproportionation or an additional
      one-electron oxidation to form a quinone imine. Overall, these studies suggest
      that 5-OHTBZ can also play a role in TBZ-induced toxicity via its bioactivation
      by P450 and peroxidases.

PMID- 16434548
TI  - Induction and recovery time course of rat brain CYP2E1 after nicotine treatment.
AB  - CYP2E1, the primary ethanol-metabolizing cytochrome P450, metabolizes endogenous
      substrates (e.g., arachidonic acid) and drugs (e.g., acetaminophen,
      chlorzoxazone) and bioactivates procarcinogens (e.g., tobacco-specific
      nitrosamines) and toxins (e.g., carbon tetrachloride). Nicotine from tobacco
      smoke may contribute to the enhanced hepatic CYP2E1 activity in smokers. We have
      previously shown that chronic nicotine treatment can increase CYP2E1 in rat liver
      and brain. In this study, induction of brain CYP2E1 was assessed after a single
      acute or a 7-day chronic treatment with saline or nicotine (1 mg/kg s.c.), with
      sacrifice performed at various times after the last injection. Chronic 7-day
      nicotine treatment showed the highest levels of CYP2E1 12 h after the last
      injection in frontal cortex (1.4-fold, p < 0.05) versus 8 h in hippocampus (1.8
      fold, p < 0.01) and cerebellum (1.4-fold, p < 0.05), returning to basal levels by
      24 h. In contrast, acute nicotine treatment did not induce CYP2E1 in frontal
      cortex and hippocampus but increased CYP2E1 in cerebellum 8 h after treatment
      (1.6-fold, p < 0.01). Brain CYP2E1 mRNA levels did not increase after chronic
      nicotine treatment, suggesting nontranscriptional regulation. Thus, humans
      exposed to nicotine may have altered CYP2E1-mediated metabolism of centrally
      acting drugs and toxins as well as altered toxicity because of oxidative stress
      caused by CYP2E1. Those affected may include current and passive smokers and
      people that may be treated with nicotine such as smokers and, potentially,
      patients with Alzheimer's, Parkinson's disease, or ulcerative colitis.

PMID- 16434549
TI  - Interactions of amoxicillin and cefaclor with human renal organic anion and
      peptide transporters.
AB  - Amoxicillin and cefaclor are two of the widely used beta-lactam antibiotics in
      the treatment of urinary tract infections. Both drugs are eliminated mainly by
      the kidney and rely on renal excretion to exert their antibacterial activities in
      the urinary tract. Previous studies have suggested the involvement of organic
      anion and oligopeptide transporters in membrane transport of beta-lactams. The
      objective of the current study was to examine the kinetics of amoxicillin and
      cefaclor interactions with human renal transporters human organic anion
      transporter 1 (hOAT1), human peptide transporter 1 (hPepT1), and human peptide
      transporter 2 (hPepT2) in detail, both as substrates and as inhibitors. Using
      fluorescence protein tagging and cell sorting, we established Madin-Darby canine
      kidney cell lines stably expressing highly functional hOAT1, hPepT1, and hPepT2.
      Amoxicillin and cefaclor inhibited hOAT1-mediated [(3)H]para-aminohippuric acid
      uptake (K(i) = 11.0 and 1.15 mM, respectively). However, our uptake study
      revealed that neither drug was transported by hOAT1. Amoxicillin and cefaclor
      competitively inhibited hPepT2-mediated [(3)H]glycylsarcosine uptake (K(i) = 733
      and 65 muM, respectively), whereas much lower affinity for hPepT1 was observed
      with both antibiotics. Direct uptake studies demonstrated that amoxicillin and
      cefaclor were transported by hPepT1 and hPepT2. Kinetic analysis showed that
      hPepT2-mediated uptake of both drugs was saturable with K(m) of 1.04 mM for
      amoxicillin and 70.2 muM for cefaclor. hPepT2, and to a lesser extent hPepT1, may
      play an important role in apical transport of amoxicillin and cefaclor in the
      renal tubule. hOAT1, in contrast, is not involved in basolateral uptake of these
      antibiotics.

PMID- 16434550
TI  - Grb10 mediates insulin-stimulated degradation of the insulin receptor: a
      mechanism of negative regulation.
AB  - Growth factor receptor-bound protein 10 (Grb10) is an adapter protein that
      interacts with a number of tyrosine-phosphorylated growth factor receptors,
      including the insulin receptor (IR). To investigate the role of Grb10 in insulin
      signaling, we generated cell lines in which the expression levels of Grb10 are
      either overexpressed by stable transfection or suppressed by RNA interference. We
      found that suppressing endogenous Grb10 expression led to increased IR protein
      levels, whereas overexpression of Grb10 led to reduced IR protein levels.
      Altering Grb10 expression levels had no effect on the mRNA levels of IR,
      suggesting that the modulation occurs at the protein level. Reduced IR levels
      were also observed in cells with prolonged insulin treatment, and this reduction
      was inhibited in Grb10-deficient cells. The insulin-induced IR reduction was
      greatly reversed by MG-132, a proteasomal inhibitor, but not by chloroquine, a
      lysosomal inhibitor. IR underwent insulin-stimulated ubiquitination in cells, and
      this ubiquitination was inhibited in the Grb10-suppressed cell line. Together,
      our results suggest that, in addition to inhibiting IR kinase activity by
      directly binding to the IR, Grb10 also negatively regulates insulin signaling by
      mediating insulin-stimulated degradation of the receptor.

PMID- 16434551
TI  - Colocalization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6
      muscle cells: evidence of a mitochondrial lactate oxidation complex.
AB  - Results of previous studies suggested a role of mitochondria in intracellular and
      cell-cell lactate shuttles. Therefore, by using a rat-derived L6 skeletal muscle
      cell line and confocal laser-scanning microscopy (CLSM), we examined the cellular
      locations of mitochondria, lactate dehydrogenase (LDH), the lactate-pyruvate
      transporter MCT1, and CD147, a purported chaperone protein for MCT1. CLSM showed
      that LDH, MCT1, and CD147 are colocalized with the mitochondrial reticulum.
      Western blots showed that cytochrome oxidase (COX), NADH dehydrogenase, LDH,
      MCT1, and CD147 are abundant in mitochondrial fractions of L6 cells. Interactions
      among COX, MCT1, and CD147 in mitochondria were confirmed by immunoblotting after
      immunoprecipitation. These findings support the presence of a mitochondrial
      lactate oxidation complex associated with the COX end of the electron transport
      chain that might explain the oxidative catabolism of lactate and, hence,
      mechanism of the intracellular lactate shuttle.

PMID- 16434552
TI  - Increase in S6K1 phosphorylation in human skeletal muscle following resistance
      exercise occurs mainly in type II muscle fibers.
AB  - To investigate the in vivo effects of resistance exercise on translational
      control in human skeletal muscle, we determined the phosphorylation of AMP
      activated kinase (AMPK), eukaryotic initiation factor 4E-binding protein (4E
      BP1), p70/p85-S6 protein kinase (S6K1), and ribosomal S6 protein (S6).
      Furthermore, we investigated whether changes in the phosphorylation of S6K1 are
      muscle fiber type specific. Eight male subjects performed a single high-intensity
      resistance exercise session. Muscle biopsies were collected before and
      immediately after exercise and after 30 and 120 min of postexercise recovery. The
      phosphorylation statuses of AMPK, 4E-BP1, S6K1, and S6 were determined by Western
      blotting with phospho-specific and pan antibodies. To determine fiber type
      specific changes in the phosphorylation status of S6K1, immunofluorescence
      microscopy was applied. AMPK phosphorylation was increased approximately
      threefold immediately after resistance exercise, whereas 4E-BP1 phosphorylation
      was reduced to 27 +/- 6% of preexercise values. Phosphorylation of S6K1 at
      Thr421/Ser424 was increased 2- to 2.5-fold during recovery but did not induce a
      significant change in S6 phosphorylation. Phosphorylation of S6K1 was more
      pronounced in the type II vs. type I muscle fibers. Before exercise,
      phosphorylated S6K1 was predominantly located in the nuclei. After 2 h of
      postexercise recovery, phospho-S6K1 was primarily located in the cytosol of type
      II muscle fibers. We conclude that resistance exercise effectively increases the
      phosphorylation of S6K1 on Thr421/Ser424, which is not associated with a
      substantial increase in S6 phosphorylation in a fasted state.

PMID- 16434553
TI  - Resveratrol, a red wine antioxidant, possesses an insulin-like effect in
      streptozotocin-induced diabetic rats.
AB  - Aberrant energy metabolism is one characteristic of diabetes mellitus (DM). Two
      types of DM have been identified, type 1 and type 2. Most of type 2 DM patients
      eventually become insulin dependent because insulin secretion by the islets of
      Langerhans becomes exhausted. In the present study, we show that resveratrol
      (3,5,4'-trihydroxylstilbene) possesses hypoglycemic and hypolipidemic effects in
      streptozotocin-induced DM (STZ-DM) rats. In resveratrol-treated STZ-DM rats, the
      plasma glucose concentration on day 14 was reduced by 25.3 +/- 4.2%, and the
      triglyceride concentration was reduced by 50.2 +/- 3.2% compared with the vehicle
      treated rats. In STZ-nicotinamide DM rats, the plasma glucose concentration on
      day 14 was reduced by 20.3 +/- 4.2%, and the triglyceride concentration was
      reduced by 33.3 +/- 2.2% compared with the vehicle-treated rats. Resveratrol
      administration ameliorates common DM symptoms, such as body weight loss,
      polyphagia, and polydipsia. In STZ-nicotinamide DM rats, resveratrol
      administration significantly decreased insulin secretion and delayed the onset of
      insulin resistance. Further studies showed that glucose uptake by hepatocytes,
      adipocytes, and skeletal muscle and hepatic glycogen synthesis were all
      stimulated by resveratrol treatment. Because the stimulation of glucose uptake
      was not attenuated in the presence of an optimal amount of insulin in insulin
      responsive cells, the antihyperglycemic effect of resveratrol appeared to act
      through a mechanism(s) different from that of insulin.

PMID- 16434554
TI  - Inhibition of mammalian translation initiation by volatile anesthetics.
AB  - Volatile anesthetics are essential for modern medical practice, but sites and
      mechanisms of action for any of their numerous cellular effects remain largely
      unknown. Previous studies with yeast showed that volatile anesthetics induce
      nutrient-dependent inhibition of growth through mechanisms involving inhibition
      of mRNA translation. Studies herein show that the volatile anesthetic halothane
      inhibits protein synthesis in perfused rat liver at doses ranging from 2 to 6%. A
      marked disaggregation of polysomes occurs, indicating that inhibition of
      translation initiation plays a key role. Dose- and time-dependent alterations
      that decrease the function of a variety of translation initiation processes are
      observed. At 6% halothane, a rapid and persistent increase in phosphorylation of
      the alpha-subunit of eukaryotic translation initiation factor (eIF)2 occurs. This
      is accompanied by inhibition of activity of the guanine nucleotide exchange
      factor eIF2B that is responsible for GDP-GTP exchange on eIF2. At lower doses,
      neither eIF2alpha phosphorylation nor eIF2B activity is altered. After extended
      exposure to 6% halothane, alterations in two separate responses regulated by the
      target of rapamycin pathway occur: 1) redistribution of eIF4E from its
      translation-stimulatory association with eIF4G to its translation-inactive
      complex with eIF4E-binding protein-1; and 2) decreased phosphorylation of
      ribosomal protein S6 (rpS6) with a corresponding decrease in active forms of a
      kinase that phosphorylates rpS6 (p70(S6K1)). Changes in the association of eIF4E
      and eIF4G are observed only after extended exposure to low anesthetic doses. Thus
      dose- and time-dependent alterations in multiple processes permit liver cells to
      adapt translation to variable degrees and duration of stress imposed by
      anesthetic exposure.

PMID- 16434555
TI  - Effects of the presence, absence, and overexpression of uncoupling protein-3 on
      adiposity and fuel metabolism in congenic mice.
AB  - Uncoupling protein-3 (UCP3) is a poorly understood mitochondrial inner membrane
      protein expressed predominantly in skeletal muscle. The aim of this study was to
      examine the effects of the absence or constitutive physiological overexpression
      of UCP3 on whole body energy metabolism, glucose tolerance, and muscle
      triglyceride content. Congenic male UCP3 knockout mice (Ucp3-/-), wild-type, and
      transgenic UCP3 overexpressing (UCP3Tg) mice were fed a 10% fat diet for 4 or 8
      mo after they were weaned. UCP3Tg mice had lower body weights and were less
      metabolically efficient than wild-type or Ucp3-/- mice, but they were not
      hyperphagic. UCP3Tg mice had smaller epididymal white adipose tissue and brown
      adipose tissue (BAT) depots; however, there were no differences in muscle
      weights. Glucose and insulin tolerance tests revealed that both UCP3Tg and Ucp3-/
      mice were protected from development of impaired glucose tolerance and were more
      sensitive to insulin. 2-Deoxy-D-[1-3H]glucose tracer studies showed increased
      uptake of glucose into BAT and increased storage of liver glycogen in Ucp3-/-
      mice. Assessments of intramuscular triglyceride (IMTG) revealed decreases in
      quadriceps of UCP3Tg mice compared with wild-type and Ucp3-/- mice. When
      challenged with a 45% fat diet, Ucp3-/- mice showed increased accumulation of
      IMTG compared with wild-type mice, which in turn had greater IMTG than UCP3Tg
      mice. Results are consistent with a role for UCP3 in preventing accumulation of
      triglyceride in both adipose tissue and muscle.

PMID- 16434556
TI  - Exercise training decreases the concentration of malonyl-CoA and increases the
      expression and activity of malonyl-CoA decarboxylase in human muscle.
AB  - The study was designed to evaluate whether changes in malonyl-CoA and the enzymes
      that govern its concentration occur in human muscle as a result of physical
      training. Healthy, middle-aged subjects were studied before and after a 12-wk
      training program that significantly increased VO2 max by 13% and decreased intra
      abdominal fat by 17%. Significant decreases (25-30%) in the concentration of
      malonyl-CoA were observed after training, 24-36 h after the last bout of
      exercise. They were accompanied by increases in both the activity (88%) and mRNA
      (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the
      phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The
      abundance of peroxisome proliferator-activated receptor (PPAR)gamma coactivator
      1alpha (PGC-1alpha), a regulator of transcription that has been linked to the
      mediation of MCD expression by PPARalpha, was also increased (3-fold). In studies
      also conducted 24-36 h after the last bout of exercise, no evidence of increased
      whole body insulin sensitivity or fatty acid oxidation was observed during an
      euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonyl
      CoA is diminished in muscle after physical training, most likely because of PGC
      1alpha-mediated increases in MCD expression and activity. These changes persist
      after the increases in AMPK activity and whole body insulin sensitivity and fatty
      acid oxidation, typically caused by an acute bout of exercise in healthy
      individuals, have dissipated.

PMID- 16434557
TI  - In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell
      disease.
AB  - Despite reports of lower GSH concentration in sickle cell disease (SCD), the in
      vivo kinetic mechanism(s) responsible for GSH deficiency is unknown. To determine
      whether suppressed synthesis was responsible for the lower erythrocyte GSH
      concentration, we used a primed intermittent infusion of [(2)H(2)]glycine to
      measure erythrocyte GSH synthesis in vivo in 23 individuals with homozygous
      beta(s) SCD and 8 healthy controls. Erythrocyte cysteine concentration, the rate
      limiting precursor for GSH synthesis, plasma markers of oxidant damage, and
      dietary intakes of energy and protein were also measured. Compared with values of
      controls, SCD subjects had significantly lower erythrocyte GSH (P < 0.04) and
      cysteine concentrations (P < 0.004) but significantly faster fractional rates of
      GSH synthesis (P < 0.02). The absolute rates of GSH synthesis in SCD subjects
      compared with control subjects was greater by approximately 57% (P = 0.062).
      However, the concentrations of markers of oxidative damage, plasma derivatives of
      reactive oxygen metabolites, plasma nitrotyrosine, urinary isoprostane-to
      creatinine ratio, and GSH-to-GSSG ratio, as well as dietary intakes of energy,
      protein, and GSH precursor amino acids, were not different between SCD subjects
      and controls. The findings of this study suggest that the lower erythrocyte GSH
      of SCD patients is not due to suppressed synthesis or impaired regeneration but
      rather to increased consumption. In addition, the lower erythrocyte cysteine
      concentration plus the faster rate of GSH synthesis strongly suggest that the
      endogenous cysteine supply is not sufficient to meet all anabolic demands; hence,
      cysteine may be a conditionally essential amino acid in individuals with SCD.

PMID- 16434558
TI  - Decreased nuclear hormone receptor expression in the livers of mice in late
      pregnancy.
AB  - During the third trimester of pregnancy, there is an increase in serum
      triglyceride and cholesterol levels. The mechanisms accounting for these changes
      in lipid metabolism during pregnancy are unknown. We hypothesized that, during
      pregnancy, the expression of nuclear hormone receptors involved in regulating
      lipid metabolism would decrease. In 19-day pregnant mice, serum triglyceride and
      non-HDL cholesterol levels were significantly increased, whereas total
      cholesterol was slightly decreased, because of a decrease in the HDL fraction.
      Peroxisome proliferator-activated receptor (PPAR)alpha, PPARbeta/delta, and
      PPARgamma, liver X receptor (LXR)alpha and LXRbeta, farnesoid X receptor (FXR),
      and retinoid X receptor (RXR)alpha, RXRbeta, and RXRgamma mRNA levels were
      significantly decreased in the livers of 19-day pregnant mice. Additionally, the
      expressions of thyroid receptor (TR)alpha, pregnane X receptor, sterol regulatory
      element-binding proteins (SREBP)-1a, SREBP-1c, SREBP-2, and liver receptor
      homolog 1 were also decreased, whereas the expression of TRbeta, constitutive
      androstane receptor, and hepatic nuclear factor 4 showed no significant change.
      mRNA levels of the PPAR target genes carnitine-palmitoyl transferase 1alpha and
      acyl-CoA oxidase, the LXR target genes SREBP1c, ATP-binding cassettes G5 and G8,
      the FXR target gene SHP, and the TR target genes malic enzyme and Spot14 were all
      significantly decreased. Finally, the expressions of PPARgamma coactivator (PGC)
      1alpha and PGC-1beta, known activators of a number of nuclear hormone receptors,
      were also significantly decreased. The decreases in expression of RXRs, PPARs,
      LXRs, FXR, TRs, SREBPs, and PGC-1s could contribute to the alterations in lipid
      metabolism during late pregnancy.

PMID- 16434560
TI  - Epidemiology of vancomycin-induced neutropenia in patients receiving home
      intravenous infusion therapy.
AB  - BACKGROUND: Vancomycin is frequently used to manage serious resistant gram
      positive infections. Neutropenia, whose epidemiology has not been well
      characterized, is a potentially serious adverse event associated with the use of
      vancomycin. OBJECTIVE: To characterize the incidence and risk factors for
      development of vancomycin-induced neutropenia in patients treated with home
      intravenous vancomycin therapy. METHODS: A retrospective chart review was
      conducted of adult patients receiving vancomycin therapy through the University
      of New Mexico Home Intravenous Infusion Clinic between January 1998 and December
      2004. Data collection included demographics, comorbid conditions, dose and
      duration of vancomycin therapy, indications for vancomycin use, vancomycin
      concentrations, all concurrent medications, laboratory data, culture and
      susceptibility data, reasons for antibiotic alteration or discontinuations, all
      other recorded adverse events, management of adverse events, and outcomes of
      adverse events. RESULTS: A total of 372 charts of patients managed through the
      clinic were reviewed and 114 patients treated with vancomycin were identified.
      Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%)
      cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less.
      The mean +/- SD duration of vancomycin therapy and time to neutropenia were 32 +/
      29 and 26 +/- 15 days, respectively. Laboratory monitoring was performed on a
      weekly basis and resolution of vancomycin-induced neutropenia occurred promptly
      after discontinuation. Total vancomycin doses used and serum concentrations were
      not associated with the development of neutropenia. CONCLUSIONS: Vancomycin
      induced neutropenia may occur at a higher frequency than previously reported.
      Clinicians should monitor hematologic parameters at least weekly in patients
      receiving home intravenous vancomycin therapy.

PMID- 16434561
TI  - Outcomes of bupropion therapy for smoking cessation during routine clinical use.
AB  - BACKGROUND: Knowledge pertaining to the effectiveness of smoking cessation
      treatments and patient characteristics that may affect success may enable smokers
      and clinicians to select individualized treatment for each patient and ultimately
      increase the success rate of smoking cessation in general. OBJECTIVE: To evaluate
      the effectiveness of bupropion as a smoking cessation agent when used in routine
      clinical practice. METHODS: This was a prospective, observational study with a
      one year follow-up period. Adult smokers presenting to community pharmacies in
      British Columbia, Canada, with an index prescription for bupropion for smoking
      cessation (N = 205) were eligible. The primary outcome was the biochemically
      validated 12 month point abstinence (PA) rate from smoking. Secondary outcomes
      included the frequency of adverse events, patterns of bupropion use in routine
      clinical practice, and possible predictors of bupropion effectiveness. RESULTS:
      The validated 12 month PA rate was 21.0%. Of subjects who reported taking at
      least one dose of bupropion, 70.4% (126/179) experienced at least one adverse
      event and 29.6% (53/179) reported stopping the drug due to adverse effects.
      Greater length of time on bupropion (OR 0.98) and a lower cigarette pack-year
      history (OR 1.05) were associated with an increase in the odds of smoking
      cessation. CONCLUSIONS: Subjects receiving bupropion in a real-life setting
      exhibited a similar abstinence rate at 12 months as has been observed in the
      active drug groups of placebo-controlled clinical trials. However, the patterns
      of use and discontinuation rate due to adverse events differed substantially from
      those observed in early efficacy studies.

PMID- 16434562
TI  - Role of buprenorphine in the management of heroin addiction.
AB  - OBJECTIVE: To review buprenorphine and explore its role in the treatment of
      heroin dependence. DATA SOURCES: Articles were identified through a search of
      MEDLINE (1966-February 2005) using the key terms buprenorphine, heroin, opioid,
      addiction, and methadone. DATA SYNTHESIS: Buprenorphine appears to provide
      potential advantages over methadone. Two Cochrane meta-analyses were evaluated on
      the use of buprenorphine in opioid dependence-one in the management of opioid
      dependence and the other in the management of opioid withdrawal. CONCLUSIONS:
      Buprenorphine offers several advantages for the treatment of heroin addiction. As
      maintenance treatment, buprenorphine is effective, but not more effective than
      methadone. In the management of opioid withdrawal, buprenorphine may be better
      tolerated than clonidine or methadone.

PMID- 16434563
TI  - Diagnoses and antipsychotic treatment among youths in a public mental health
      system.
AB  - BACKGROUND: The use of antipsychotics, namely newer atypical agents, has
      increased significantly in children and adolescents. It is important to examine
      diagnoses associated with antipsychotic treatment in youths. OBJECTIVE: To
      evaluate trends in psychiatric diagnoses of children and adolescents in a public
      mental health system who were prescribed antipsychotics. METHODS: Children and
      adolescents, up to the age of 19 years, who were prescribed an antipsychotic
      between January 1998 and December 2001 were identified using the Texas Medicaid
      Vendor Drug database. Patient identification numbers were then cross-linked to
      the Client Assignment and Registration database of the Texas Department of Mental
      Health and Mental Retardation to extract diagnostic data. RESULTS: Disruptive
      behavioral disorders accounted for the highest percentage (35%) of diagnoses
      associated with children and adolescents receiving antipsychotic treatment and
      mental healthcare services. Depressive disorders were the second most common
      diagnosis (18%), and bipolar disorders accounted for roughly 12% of all
      diagnoses. Approximately 3% of children and adolescents did not have a
      psychiatric diagnosis. The percentage of youths with comorbid psychiatric
      diagnoses decreased over time. CONCLUSIONS: Although disruptive behavioral
      disorders accounted for a large percentage of antipsychotic use in this
      population, these findings suggest that antipsychotics are being used to treat
      other psychiatric diagnoses, for which limited supporting data exist. Future
      research in children and adolescents should aim to provide needed efficacy and
      safety data of antipsychotics across the spectrum of neuropsychiatric disorders.

PMID- 16434565
TI  - Protease-activated receptor-2 peptides activate neurokinin-1 receptors in the
      mouse isolated trachea.
AB  - Protective roles for protease-activated receptor-2 (PAR(2)) in the airways
      including activation of epithelial chloride (Cl(-)) secretion are based on the
      use of presumably PAR(2)-selective peptide agonists. To determine whether PAR(2)
      peptide-activated Cl(-) secretion from mouse tracheal epithelium is dependent on
      PAR(2), changes in ion conductance across the epithelium [short-circuit current
      (I(SC))] to PAR(2) peptides were measured in Ussing chambers under voltage clamp.
      In addition, epithelium- and endothelium-dependent relaxations to these peptides
      were measured in two established PAR(2) bioassays, isolated ring segments of
      mouse trachea and rat thoracic aorta, respectively. Apical application of the
      PAR(2) peptide SLIGRL caused increases in I(SC), which were inhibited by three
      structurally different neurokinin receptor-1 (NK(1)R) antagonists and inhibitors
      of Cl(-) channels but not by capsaicin, the calcitonin gene-related peptide
      (CGRP) receptor antagonist CGRP(8-37), or the nonselective cyclooxygenase
      inhibitor indomethacin. Only high concentrations of trypsin caused an increase in
      I(SC) but did not affect the responses to SLIGRL. Relaxations to SLIGRL in the
      trachea and aorta were unaffected by the NK(1)R antagonist nolpitantium (SR
      140333) but were abolished by trypsin desensitization. The rank order of potency
      for a range of peptides in the trachea I(SC) assay was 2-furoyl-LIGRL > SLCGRL >
      SLIGRL = SLIGRT > LSIGRL compared with 2-furoyl-LIGRL > SLIGRL > SLIGRT > SLCGRL
      (LSIGRL inactive) in the aorta relaxation assay. In the mouse trachea, PAR(2)
      peptides activate both epithelial NK(1)R coupled to Cl(-) secretion and PAR(2)
      coupled to prostaglandin E(2)-mediated smooth muscle relaxation. Such a potential
      lack of specificity of these commonly used peptides needs to be considered when
      roles for PAR(2) in airway function in health and disease are determined.

PMID- 16434564
TI  - In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl
      indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (indacaterol), a
      novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of action.
AB  - Here, we describe the preclinical pharmacological profile of 5-[(R)-2-(5,6
      diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one
      (indacaterol), a novel, chirally pure inhaled beta(2) adrenoceptor agonist, in
      comparison with marketed drugs. Indacaterol is close to a full agonist at the
      human beta(2) adrenoceptor (E(max) = 73 +/- 1% of the maximal effect of
      isoprenaline; pEC(50) = 8.06 +/- 0.02), whereas salmeterol displays only partial
      efficacy (38 +/- 1%). The functional selectivity profile of indacaterol over
      beta(1) human adrenoceptors is similar to that of formoterol, whereas its beta(3)
      adrenoceptor selectivity profile is similar to that of formoterol and salbutamol.
      In isolated superfused guinea pig trachea, indacaterol has a fast onset of action
      (30 +/- 4 min) similar to formoterol and salbutamol, and a long duration of
      action (529 +/- 99 min) comparable with salmeterol. In the conscious guinea pig,
      when given intratracheally as a dry powder, indacaterol inhibits 5
      hydroxytryptamine-induced bronchoconstriction for at least 24 h, whereas
      salmeterol, formoterol, and salbutamol have durations of action of 12, 4, and 2
      h, respectively. When given via nebulization to anesthetized rhesus monkeys, all
      of the compounds dose-dependently inhibit methacholine-induced
      bronchoconstriction, although indacaterol produces the most prolonged
      bronchoprotective effect and induces the lowest increase in heart rate for a
      similar degree of antibronchoconstrictor activity. In conclusion, the preclinical
      profile of indacaterol suggests that this compound has a superior duration of
      action compatible with once-daily dosing in human, together with a fast onset of
      action and an improved cardiovascular safety profile over marketed inhaled
      beta(2) adrenoceptor agonists.

PMID- 16434566
TI  - Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats
      attenuates the effects of a subsequent challenge with MDMA or a 5
      hydroxytryptamine(1A) receptor agonist.
AB  - Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may
      escalate their dose because of the development of tolerance. We examined the
      influence of intermittent adolescent MDMA exposure on the behavioral,
      physiological, and neurochemical responses to a subsequent MDMA "binge" or to a 5
      hydroxytryptamine(1A) (5-HT(1A)) receptor challenge. Male Sprague-Dawley rats
      were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs)
      35 to 60. One week later on PD 67, animals were challenged with either multiple
      doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT(1A) agonist
      8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent
      MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA
      challenge, completely blocked the locomotor hypoactivity otherwise observed on
      the day after the challenge, and also prevented MDMA-induced serotonin
      neurotoxicity assessed on PD 74 by measuring regional [(3)H]citalopram binding to
      the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a
      partial attenuation of the serotonin syndrome but not the hypothermic response to
      the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration
      on regional [(3)H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) binding to 5
      HT(1A) receptors in the brain or spinal cord. These results suggest that chronic,
      intermittent MDMA exposure during adolescence induces neuroadaptive changes that
      can protect against the adverse consequences of a subsequent dose escalation. On
      the other hand, the same exposure pattern appears to produce a partial 5-HT(1A)
      receptor desensitization, which may negatively influence the therapeutic
      responses of chronic MDMA users treated with serotonergic agents for various
      affective or anxiety disorders.

PMID- 16434567
TI  - Preclinical pharmacology of a nonsteroidal ligand for androgen receptor-mediated
      imaging of prostate cancer.
AB  - Proper management of prostate cancer patients is highly dependent on the spread
      of the disease. High expression levels of the androgen receptor (AR) in prostate
      tumor offer a target for identifying cancer metastasis. We investigated the use
      of nonsteroidal AR ligands for receptor-mediated imaging as a diagnostic tool for
      prostate cancer staging. Compound S-26 [S-3-(4-fluorophenoxy)-2-hydroxy-2-methyl
      N-(4-cyano-3-iodophenyl)-propionamide]was identified from a series of iodinated
      ether-linked derivatives of bicalutamide due to its high-AR binding affinity of
      3.3 nM (which is similar to testosterone and approximately 25% of the binding
      affinity of dihydrotestosterone) in an in vitro competitive binding assay using
      rat prostate cytosol. Furthermore, S-26 exhibited a greater binding affinity
      (K(i) = 4.4 nM) in a whole-cell binding assay using COS-7 cells transfected with
      human AR than testosterone (K(i) = 32.9 nM) and dihydrotestosterone (K(i) = 45.4
      nM). We also confirmed that sex hormone-binding globulin (SHBG), a plasma protein
      that binds steroids with high affinity, does not bind with S-26. Cotransfection
      studies with the estrogen, progesterone, and glucocorticoid receptor indicated
      that S-26 does not cross-react with other members of the steroid hormone receptor
      family. The nonsteroidal structure, high-AR binding affinity, specificity, and
      lack of binding to SHBG indicate that S-26 exhibits favorable properties for
      further development as an imaging agent for prostate cancer.

PMID- 16434568
TI  - Mouse model of inducible nephrogenic diabetes insipidus produced by floxed
      aquaporin-2 gene deletion.
AB  - Transgenic mouse models of defective urinary concentrating ability produced by
      deletion of various membrane transport or receptor proteins, including aquaporin
      2 (AQP2), are associated with neonatal mortality from polyuria. Here, we report
      an inducible mouse model of AQP2 gene deletion with severe polyuria in adult
      mice. LoxP sequences were inserted into introns 1 and 2 in the mouse AQP2 gene by
      homologous recombination in embryonic stem cells. Mating of germ-line AQP2-loxP
      mice with tamoxifen-inducible Cre-expressing mice produced offspring with
      inducible homozygous Cre-AQP2-loxP, which had a normal phenotype. Tamoxifen
      injections over 10 days resulted in AQP2 gene excision, with undetectable full
      length AQP2 transcript in kidney and a >95% reduction in immunoreactive AQP2
      protein. Urine osmolality decreased from approximately 2,000 to <500
      mosmol/kgH(2)O after 4-5 days, with urine output increasing from 2 to 25 ml/day.
      Urine osmolality did not increase after water deprivation. Interestingly, AQP3
      protein expression in the collecting duct was increased by about fivefold after
      AQP2 gene excision. Mild renal damage was seen after 6 wk of polyuria, with
      collecting duct dilatation, yet normal creatinine clearance and serum
      chemistries. These results establish the first adult model of nephrogenic
      diabetes insipidus (NDI) caused by AQP2 deficiency, with daily urine output
      comparable to body weight, although remarkable preservation of renal function
      compared with non-inducible NDI models.

PMID- 16434569
TI  - Changes in subcellular distribution of the ammonia transporter, Rhcg, in response
      to chronic metabolic acidosis.
AB  - The primary mechanism by which the kidneys mediate net acid excretion is through
      ammonia metabolism. In the current study, we examined whether chronic metabolic
      acidosis, which increases ammonia metabolism, alters the cell-specific and/or the
      subcellular expression of the ammonia transporter family member, Rhcg, in the
      outer medullary collecting duct in the inner stripe (OMCDi). Chronic metabolic
      acidosis was induced in normal SD rats by HCl ingestion for 7 days; controls were
      pair-fed. The subcellular distribution of Rhcg was determined using immunogold
      electron microscopy and morphometric analyses. In intercalated cells, acidosis
      increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total
      cellular Rhcg in the apical plasma membrane. Intracellular Rhcg decreased
      significantly, and basolateral Rhcg was unchanged. Because apical plasma membrane
      length increased in parallel with apical Rhcg immunolabel, apical plasma membrane
      Rhcg density was unchanged. In principal cells, acidosis increased total Rhcg,
      apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the
      apical plasma membrane while decreasing the intracellular proportion. In contrast
      to the intercalated cell, chronic metabolic acidosis did not significantly alter
      apical boundary length; accordingly, apical plasma membrane Rhcg density
      increased. In addition, basolateral Rhcg immunolabel increased in response to
      chronic metabolic acidosis. These results indicate that in the rat OMCDi 1)
      chronic metabolic acidosis increases apical plasma membrane Rhcg in both the
      intercalated cell and principal cell where it may contribute to enhanced apical
      ammonia secretion; 2) increased apical plasma membrane Rhcg results from both
      increased total protein and changes in the subcellular distribution of Rhcg; 3)
      the mechanism of Rhcg subcellular redistribution differs in intercalated and
      principal cells; and 4) Rhcg may contribute to regulated basolateral ammonia
      transport in the principal cell.

PMID- 16434570
TI  - Stathmin-deficient mice develop fibrosis and show delayed recovery from ischemic
      reperfusion injury.
AB  - In kidneys subjected to ischemic reperfusion injury (IRI) stathmin, a tubulin
      binding protein involved in the regulation of mitosis, is expressed in
      dedifferentiated and proliferating renal tubule cells during the recovery phase.
      To ascertain the role of stathmin in the recovery from ischemic kidney injury,
      stathmin-deficient (OP18-/-) and wild-type (WT) animals were subjected to
      experimental IRI. At 3, 7, and 14 days after reperfusion serum samples and
      kidneys were collected for the examination of parameters of renal function,
      morphology, and recovery. Our studies indicate that on day 14 after reperfusion
      OP18-/- mice have significant renal failure, whereas the creatinine levels of WT
      animals have returned to baseline. Compared with WT animals OP18-/- mice had more
      extensive tubular fibrosis. The examination of proliferating cell nuclear antigen
      expression indicated that OP18-/- animals have increased proliferative or DNA
      repair activity for a more prolonged duration. The OP18-/- animals also had an
      increased number of tubules with apoptotic cells. These results suggest that in
      stathmin-deficient mice subjected to IRI, the aberrant regulation of cell cycle
      progression, not observed under normal conditions, impairs or at least delays the
      process of tubular repair and recovery after acute renal injury.

PMID- 16434571
TI  - Hypokalemia in a mouse model of Gitelman's syndrome.
AB  - Hypokalemia is a prominent feature of Gitelman syndrome and a common side effect
      of thiazide use in the treatment of hypertension. It is widely recognized that
      genetic or pharmacological inhibition of the renal thiazide-sensitive sodium
      chloride cotransporter (NCC) initiates the potentially severe renal potassium
      loss observed in these settings. Surprisingly, hypokalemia has not been detected
      in NCC (-/-) mice maintained on normal rodent diets (Schultheis PJ, Lorenz JN,
      Meneton P, Nieman ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML,
      and Shull GE. J Biol Chem 273: 29150-29155, 1998). We show that modest reduction
      of dietary potassium induced a marked reduction in plasma potassium and elevated
      renal potassium excretion in NCC (-/-) mice that was associated with a pronounced
      polydipsia and polyuria of central origin. These findings are consistent with the
      development of potassium depletion in NCC (-/-) mice and were not seen in wild
      type mice maintained on the same low-potassium diet. In addition, plasma
      aldosterone levels were significantly elevated in NCC (-/-) mice even in the
      presence of a low-potassium diet. Collectively, these findings suggest an early
      central component to the polyuria of Gitelman syndrome and show that both
      elevated aldosterone and dietary potassium content contribute to the development
      of hypokalemia in Gitelman syndrome. Therefore, NCC (-/-) mice are more sensitive
      to reductions in dietary potassium than wild-type mice and become hypokalemic,
      thus more faithfully representing the Gitelman phenotype seen in humans.

PMID- 16434572
TI  - Lithium treatment induces a marked proliferation of primarily principal cells in
      rat kidney inner medullary collecting duct.
AB  - Lithium (Li) treatment for 4 wk has previously been shown to increase the
      fraction of intercalated cells in parallel with a decrease in the fraction of
      principal cells in the kidney collecting duct (Christensen BM, Marples D, Kim YH,
      Wang W, Frokiaer J, and Nielsen S. Am J Physiol Cell Physiol 286: C952-C964,
      2004; Kim YH, Kwon TH, Christensen BM, Nielsen J, Wall SM, Madsen KM, Frokiaer J,
      and Nielsen S. Am J Physiol Renal Physiol 285: F1244-F1257, 2003). To study how
      early this fractional change starts, the origin of the cells and the possible
      mechanism behind the changes, we did time course studies in rats subjected to
      different durations of Li treatment (i.e., for 4, 10, and 15 days). Increased
      urine output was already observed at day 4 of Li treatment with decreased AQP2
      levels although not statistically significant. At days 10 and 15, both a
      significant polyuria and downregulation in AQP2 expression were observed. At day
      10, the density of H+-ATPase-positive cells was increased in the IMCD of Li
      treated rats and this was further pronounced at day 15. Some of the H+-ATPase
      positive cells did not costain with Cl-/HCO3- exchanger AE1, indicating that they
      were not fully differentiated to type A IC. By double labeling for either H+
      ATPase and proliferating-cell nuclear antigen (PCNA) or for AQP4 and PCNA, we
      found that proliferation mainly occurred in proximal IMCD cells at day 4 and it
      increased toward the middle part of the IMCD in response to prolonged Li
      treatment. Most cells expressing PCNA were stained with AQP4 but not with H+
      ATPase. Triple-labeling for H+-ATPase, AQP4, and PCNA showed a subset of cells
      negative for all three proteins or only positive for PCNA. In contrast, a 4-wk
      recovery period after 4 wk of Li treatment reversed the enhanced proliferative
      rate to the control levels. In conclusion, the Li-induced increase in the density
      of intercalated cells is associated with a high proliferative rate of principal
      cells in the IM-1 and IM-2 rather than a selective proliferation of intercalated
      cells as expected. This is likely to contribute to the remodeling of the
      collecting duct after Li treatment.

PMID- 16434574
TI  - Indoxyl sulfate induces complex redox alterations in mesangial cells.
AB  - Indoxyl sulfate is a protein metabolite that is concentrated in the serum of
      patients with chronic renal insufficiency. It also is a uremic toxin that has
      been implicated in the progression of chronic renal disease in rodent models. We
      have shown previously that mesangial cell redox status is related to activation
      of mitogen-activated protein kinases and cell proliferation, which are factors
      related to glomerular damage. We used three methods to examine the ability of
      indoxyl sulfate to alter mesangial cell redox as a possible mechanism for its
      toxicity. Indoxyl sulfate increases mesangial cell reduction rate in a
      concentration-dependent manner as demonstrated by redox microphysiometry.
      Alterations occurred at concentrations as low as 100 microM, with more marked
      alterations occurring at higher concentrations associated with human renal
      failure. We demonstrated that indoxyl sulfate induces the production of
      intracellular reactive oxygen species (ROS) in mesangial cells (EC50 = 550
      microM) by using the ROS-sensitive fluorescent dye CM-DCF. ROS generation was
      only partially (approximately 50%) inhibited by the NADPH oxidase inhibitor
      diphenylene iodinium at low (< or = 300 microM) indoxyl sulfate concentrations.
      Diphenylene iodinium was without effect at higher concentrations of indoxyl
      sulfate. We also used electron paramagnetic spin resonance spectroscopy with
      extracellular and intracellular spin traps to show that indoxyl sulfate increases
      extracellular SOD-sensitive O2-* production and intracellular hydroxyl radical
      production that may derive from an initial O2-* burst. These results document
      that indoxyl sulfate, when applied to renal mesangial cells at pathological
      concentrations, induces rapid and complex changes in mesangial cell redox.

PMID- 16434573
TI  - Inhibition of Ras/ERK1/2 signaling protects against postischemic renal injury.
AB  - The small GTPase p21 Ras and its downstream effectors play a central role in the
      control of cell survival and apoptosis. We studied the effects of Ras/ERK1/2
      signaling inhibition on oxidative damage in cultured renal and endothelial cells
      and on renal ischemia-reperfusion injury in the rat. Primary human renal tubular
      and human endothelial ECV304 cells underwent significant cell death when
      subjected to oxidative stress. This type of stress induced robustly ERK1/2 and
      phosphoinositide 3-kinase (PI3-kinase) signaling. Inhibition of Ras/ERK1/2 with a
      farnesyl transferase inhibitor, chaetomellic acid A (S-FTI), or with PD-98059, an
      inhibitor of MEK, a kinase upstream ERK1/2, significantly reduced the fraction of
      dead cells. The inhibitor of the PI3-kinase/Akt pathway, LY-294002, failed to
      exert a protective effect. We have translated these data in a rat model of renal
      ischemic injury in vivo. In uninephrectomized animals, anesthetized with
      pentobarbital sodium (Nembutal, 50 mg/kg i.p.), 24 h after an acute ischemic
      renal insult (45-min occlusion of left renal artery) a significant fraction of
      kidney cells succumbed to cell death resulting in renal failure [glomerular
      filtration rate (GFR) 0.17 +/- 0.1 vs. 0.90 +/- 0.4 ml x min(-1) x 100 g body wt(
      1) in normal rats]. Rats treated with S-FTI maintained the renal function (GFR
      0.50 +/- 0.1 ml x min(-1) x 100 g body wt(-1)), and the kidneys showed a
      significant reduction of tubular necrosis. Reduction of ischemic damage in kidney
      and tubular cells paralleled Ha-Ras inhibition, assayed by cytosolic
      translocation of the protein. These data demonstrate that inhibition of
      farnesylation and consequently of Ras/ERK1/2 signaling significantly reduces
      acute postischemic renal injury.

PMID- 16434575
TI  - Cofilin mediates ATP depletion-induced endothelial cell actin alterations.
AB  - Ischemia and sepsis lead to endothelial cell damage, resulting in compromised
      microvascular flow in many organs. Much remains to be determined regarding the
      intracellular structural events that lead to endothelial cell dysfunction. To
      investigate potential actin cytoskeletal-related mechanisms, ATP depletion was
      induced in mouse pancreatic microvascular endothelial cells (MS1). Fluorescent
      imaging and biochemical studies demonstrated a rapid and progressive increase in
      F-actin along with a decrease in G-actin at 60 min. Confocal microscopic analysis
      showed ATP depletion resulted in destruction of actin stress fibers and
      accumulation of F-actin aggregates. We hypothesized these actin alterations were
      secondary to dephosphorylation/activation of actin-depolymerizing factor
      (ADF)/cofilin proteins. Cofilin, the predominant isoform expressed in MS1 cells,
      was rapidly dephosphorylated/activated during ATP depletion. To directly
      investigate the role of cofilin activation on the actin cytoskeleton during
      ischemia, MS1 cells were infected with adenoviruses containing the cDNAs for wild
      type Xenopus laevis ADF/cofilin green fluorescent protein [XAC(wt)-GFP], GFP, and
      the constitutively active and inactive isoforms XAC(S3A)-GFP and XAC(S3E)-GFP.
      The rate and extent of cortical actin destruction and actin aggregate formation
      were increased in ATP-depleted XAC(wt)-GFP- and XAC(S3A)-GFP-expressing cells,
      whereas increased actin stress fibers were observed in XAC(S3E)-GFP-expressing
      cells. To investigate the upstream signaling pathway of ADF/cofilin, LIM kinase 1
      GFP (LIMK1-GFP) was expressed in MS1 cells. Cells expressing LIMK1-GFP protein
      had higher levels of phosphorylated ADF/cofilin, increased stress fibers, and
      delayed F-actin cytoskeleton destruction during ATP depletion. These results
      strongly support the importance of cofilin regulation in ischemia-induced
      endothelial cell actin cytoskeleton alterations leading to cell damage and
      microvascular dysfunction.

PMID- 16434576
TI  - High birthweight and cancer: evidence and implications.

PMID- 16434578
TI  - Genetic epidemiology: the value of population differences.

PMID- 16434577
TI  - Does "clock" matter in prostate cancer?
AB  - The ancient adaptation of a 24-hour circadian clock has profound effect on our
      daily biochemical, physiologic, and behavioral processes, including the
      monitoring of sex hormone levels. Although the disruption of the circadian cycle
      has been implicated in the etiology of hormone-related female breast cancer, few
      studies have been undertaken to determine if a link exists in the development of
      the most common cancer type among men whose etiology remains largely unknown:
      hormone-related prostate cancer. Here, we hypothesize that both altered-lighted
      environments and genetic variations in genes responsible for maintaining
      circadian rhythms may result in deregulation of clock-associated biological
      processes, such as androgen expression, and consequently influence an
      individual's risk of prostate cancer. There is also a potential for the
      interaction of genetic variants and exposures, such as evening shift work.
      Confirmation of this hypothesis will add to our understanding of the role of the
      circadian clock in prostate tumorigenesis and further facilitate the development
      of novel risk and prognostic biomarkers for prostate cancer.

PMID- 16434579
TI  - Uptake of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone by Moldovan children.
AB  - The evidence of an association between childhood exposure to environmental
      tobacco smoke (ETS) and an increased risk of lung cancer is inconsistent.
      However, taking into account the existing association between lung cancer and
      adulthood ETS exposure, it is plausible that children exposed to ETS also would
      be at risk of developing lung cancer later in life. In this study, we
      investigated the uptake by Moldovan children of the tobacco-specific lung
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by measuring
      total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the sum of the NNK
      metabolites, NNAL, and its O-glucuronide and N-glucuronide (NNAL-Glucs) in urine.
      We also measured urinary cotinine and its glucuronide (total cotinine). Total
      NNAL was detected in 69 of 80 samples, including those that were low in cotinine
      (<5 ng/mL). The mean+/- SD level of total NNAL (0.09+/- 0.077 pmol/mL) was
      comparable with those observed in previous studies of children and adults exposed
      to ETS. Total NNAL correlated with total cotinine (r=0.8, P<0.0001). The mean+/-
      SD levels of total NNAL and total cotinine were higher in children who were
      exposed to ETS (0.1+/- 0.08 and 109+/- 126 pmol/mL, respectively) than in those
      who were classified as unexposed to ETS based on questionnaire data (0.049+/-
      0.016 pmol/mL and 0.043+/- 0.040 nmol/mL). The results of this study for the
      first time show widespread and considerable uptake of nicotine and the tobacco
      specific lung carcinogen NNK in Moldovan children. These results should be useful
      in heightening the awareness of the dangers of smoking and ETS exposure in this
      eastern European country.

PMID- 16434580
TI  - A randomized controlled trial of financial incentives for smoking cessation.
AB  - BACKGROUND: Although 435,000 Americans die each year of tobacco-related illness,
      only approximately 3% of smokers quit each year. Financial incentives have been
      shown to be effective in modifying behavior within highly structured settings,
      such as drug treatment programs, but this has not been shown in treating chronic
      disease in less structured settings. The objective of this study was to determine
      whether modest financial incentives increase the rate of smoking cessation
      program enrollment, completion, and quit rates in a outpatient clinical setting.
      METHODS: 179 smokers at the Philadelphia Veterans Affairs Medical Center who
      reported smoking at least 10 cigarettes per day were randomized into incentive
      and non-incentive groups. Both groups were offered a free five-class smoking
      cessation program at the Philadelphia Veterans Affairs Medical Center. The
      incentive group was also offered $20 for each class attended and $100 if they
      quit smoking 30 days post program completion. Self-reported smoking cessation was
      confirmed with urine cotinine tests. RESULTS: The incentive group had higher
      rates of program enrollment (43.3% versus 20.2%; P<0.001) and completion (25.8%
      versus 12.2%; P=0.02). Quit rates at 75 days were 16.3% in the incentive group
      versus 4.6% in the control group (P=0.01). At 6 months, quit rates in the
      incentive group were not significantly higher (6.5%) than in the control group
      (4.6%; P>0.20). CONCLUSION: Modest financial incentives are associated with
      significantly higher rates of smoking cessation program enrollment and completion
      and short-term quit rates. Future studies should consider including an incentive
      for longer-term cessation.

PMID- 16434581
TI  - Mitochondrial DNA content increase in response to cigarette smoking.
AB  - An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial
      function occurs with aging and in response to DNA-damaging agents, including
      tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA
      content in a population of individuals with varied smoking and alcohol exposure.
      Age, smoking history, ethanol intake, and other demographic data were
      characterized for 604 individuals participating in a screening study for smoking
      related upper aerodigestive malignancy. Total DNA was extracted from exfoliated
      cells in saliva. DNA from a nuclear gene, beta-actin, and two mitochondrial
      genes, cytochrome c oxidase I and II (Cox I and Cox II), were quantified by real
      time PCR. mtDNA content was correlated with age, exposure history, and other
      variables using multivariate regression analyses. A significant increase
      (P<0.001) in mtDNA content was noted in smokers (31% and 29% increase for Cox I
      and Cox II, respectively) and former smokers (31% and 34%) when compared with
      never smokers. This association persisted after adjustment for other significant
      factors including age, alcohol drinking, and income (P<0.001). Increased mtDNA
      content was positively associated with pack-years of smoking (P=0.02). Despite an
      average smoking cessation interval of 21 years in former smokers, tobacco
      cessation interval was not statistically significantly associated with mtDNA
      content. Smoking is associated with increased mtDNA content in a dose-dependent
      fashion. Mitochondrial DNA alterations in response to smoking persist for several
      decades after smoking cessation, consistent with long-term, smoking-related
      damage.

PMID- 16434582
TI  - Unlimited access to care: effect on racial disparity and prognostic factors in
      lung cancer.
AB  - STUDY OBJECTIVE: Evaluate the prognostic factors influencing lung cancer survival
      under a universal health care system and determine if access to care eliminates
      clinical outcome disparity. DESIGN: Retrospective case series review. BACKGROUND:
      Lung cancer survival is worse in men and in African Americans, thought to be
      related to poor general health in men and limited access to heath care in African
      Americans. The Military Health Care System, with unlimited access to care,
      provides an excellent setting for evaluating gender and racial disparities in
      lung cancer survival. METHODS: Lung cancers diagnosed at Walter Reed Army Medical
      Center, from 1990 to 2000, were evaluated by chart review for age, gender, race,
      smoking history, cancer history, histology, stage, and completeness of resection.
      RESULTS: Seven hundred thirteen Caucasians and 173 African Americans, 2:1 male
      predominance, had a 22% 5-year survival. Cox model analysis showed that male
      gender [hazard ratio (HR, 1.31) 95% confidence interval (95% CI), 1.02-1.68],
      advanced-stage disease (stage III: HR, 2.58; 95% CI, 1.57-4.26/stage IV: HR,
      4.20; 95% CI, 2.51-7.41), and incomplete resection (HR, 4.06; 95% CI, 2.75-5.99)
      were predictors of poor outcome; whereas bronchoalveolar carcinoma features (HR,
      0.35; 95% CI, 0.23-0.52) and smoking cessation >7 years (HR, 0.70; 95% CI, 0.49
      0.99) were predictors of favorable outcome. No ethnic differences in survival
      were observed. CONCLUSIONS: No racial disparities in survival when access to
      medical care is universal. Male gender, incomplete resection, and advanced stage
      are significant predictors of poor outcome in lung cancer.

PMID- 16434583
TI  - The relative use of eight collagenous and noncollagenous markers for diagnosis of
      skeletal metastases in breast, prostate, or lung cancer patients.
AB  - The present study was sought to assess the relative use of eight biomarkers for
      the detection of bone metastases in cancer forms frequently spreading to the
      skeleton. Participants were 161 patients with either breast, prostate, or lung
      cancer. The presence and extent of bone metastases was assessed by imaging
      techniques (computer tomography and/or magnetic resonance imaging) and Technetium
      99m scintigraphy. Serum or urinary level of the bone resorption markers
      (alphaalphaCTX, betabetaCTX, NTX, and ICTP), formation marker (BSAP), and
      osteoclastogenesis markers (osteoprotegerin, RANKL, and TRAP5b) was measured by
      commercially available immunoassays. When assessed on a group basis, all
      biomarkers, except for osteoprotegerin and RANKL, were significantly elevated in
      patients compared with those without bone metastases (P<0.05). Biomarkers had
      greater diagnostic value in breast and prostate cancer patients, yet
      alphaalphaCTX, NTx, and ICTP were able to discriminate lung cancer patients with
      or without bone metastases (P<0.05). Strong linear associations were seen between
      the extent of skeletal infiltration and levels of the different biomarkers,
      except for osteoprotegerin and RANKL. Furthermore, all biomarkers (except for
      osteoprotegerin and RANKL) were indicative at the early stage of skeletal
      involvement (one to five metastases). When expressing sensitivity as the
      percentage increase in biomarker level relative to patients without bone
      metastases, alphaalphaCTX showed the largest relative increases at each stage of
      the metastatic disease. These results suggest that closer monitoring of cancer
      patients with serial measures of biomarkers might facilitate the timely diagnosis
      of skeletal metastases.

PMID- 16434584
TI  - Estrogen and progesterone levels in nipple aspirate fluid of healthy
      premenopausal women: relationship to steroid precursors and response proteins.
AB  - BACKGROUND: Concentrations of estrogen and progesterone within the breast could
      provide a better reflection of breast cancer risk than levels in the circulation.
      We developed highly sensitive immunoassays for multiple steroid hormones and
      proteins in the nipple aspirate fluid (NAF), which can be obtained noninvasively
      with a simple suction device. Previous studies showed that NAF hormone levels are
      strongly correlated between breasts and within a single breast over time and are
      predictably related to hormone replacement therapy or use of oral contraceptives.
      This study evaluates the relationship of NAF estrogen and progesterone levels to
      those in serum and saliva, the relationship of NAF estradiol to androgenic and
      estrogenic precursors in NAF, and the relationship of NAF hormone levels to those
      of response proteins such as cathepsin D and epidermal growth factor (EGF).
      METHODS: Normal premenopausal women collected saliva daily and donated blood and
      NAF in the midluteal phases of menstrual cycles at intervals of 0, 4, 12, and 15
      months. Analytes were measured by immunoassays after solvent fractionation. Log
      transformed values were fit to repeated measures analysis of covariance models to
      ascertain associations between analytes. RESULTS: Small nonsignificant
      associations were found between NAF and serum or salivary estradiol. However,
      progesterone in NAF was significantly associated with progesterone in serum and
      saliva (R=0.18 and 0.32, respectively). Within NAF, the estradiol precursors
      estrone sulfate, androstenedione, and dehydroepiandrosterone were significantly
      associated with estradiol concentration (P<0.06), and a multiprecursor model
      explained the majority of variance in NAF estradiol (model R(2)=0.83). Cathepsin
      D and EGF in NAF could not be predicted from serum or salivary steroid
      measurements; however, both could be predicted from estradiol and its precursors
      in NAF (model R(2)=0.70 and 0.93, respectively). CONCLUSIONS: By showing
      consistent associations between estradiol and its precursors and response
      proteins, these data provide support for the biological validity of NAF hormone
      measurements and for the importance of steroid interconversion by aromatase and
      sulfatase within the breast. The low correlation between estrogen levels in NAF
      and those in serum or saliva suggests that the degree of association between
      estrogen or its androgen precursor levels and risk of breast cancer observed in
      epidemiologic studies using serum estimates might be highly attenuated.

PMID- 16434585
TI  - Reduction in breast cancer mortality from organized service screening with
      mammography: 1. Further confirmation with extended data.
AB  - BACKGROUND: In an earlier publication, our evaluation of data from breast cancer
      screening programs in seven Swedish counties suggested a 40% reduction in
      incidence-based breast cancer mortality among women actually screened. In the
      current study, we expand the previous analysis from seven counties to 13 large
      areas within nine counties, including six of the original counties and seven
      additional areas, examine a longer period of follow-up (20-44 years), apply new
      analytic methods for the evaluation of incidence-based breast cancer mortality,
      and estimate the number needed to screen to save one life. METHODS: Data from six
      of the original counties (one being excluded as it does not yet have 10 years of
      follow-up after the initiation of screening), with increased follow-up, and seven
      additional large areas, within three counties, representing approximately 45% of
      Swedish women, provide information about age at diagnosis, age at death, and
      screening history for 542,187 women in the prescreening and 566,423 women in the
      screening epochs. Regardless of year of diagnosis, there were a total of 6,231
      deaths due to breast cancer in the period of study as a whole. Of these, 4,778
      were incidence-based deaths in the two epochs, i.e., death among cases diagnosed
      within either the prescreening or screening period. Data were analyzed using
      Poisson regression and adjusted, when necessary, for self-selection bias,
      contemporaneous changes in incidence, and changes in mortality independent of
      screening. RESULTS: Attendance was uniformly high, averaging 75% in the screening
      epochs. Recall rates for assessment varied from 4% to 5% at the first round of
      screening and approximately 3% at later rounds. Detection rates averaged five
      breast cancers per 1,000 women screened in the first round, and four breast
      cancers per 1,000 women screened in subsequent rounds. There was a significant
      45% reduction in incidence-based breast cancer mortality among screened women in
      the screening epoch relative to incidence-based breast cancer mortality in the
      prescreening epoch (relative risk, 0.55; 95% confidence intervals, 0.51-0.59).
      After adjusting for self-selection bias, there still was a significant 43%
      reduction in incidence-based breast cancer mortality associated with screening
      (relative risk, 0.57; 95% confidence intervals, 0.53-0.62). CONCLUSIONS: These
      results indicate a reduction in breast cancer mortality of between 40% and 45% in
      association with screening, after adjustment for self-selection bias. These
      results were obtained with modest human costs: the number needed to screen to
      save one life was estimated as 472.

PMID- 16434586
TI  - Reduction in breast cancer mortality from the organised service screening with
      mammography: 2. Validation with alternative analytic methods.
AB  - BACKGROUND: In our companion article, incidence-based mortality analysis of data
      from breast cancer screening programs in 13 areas in Sweden indicated a 40% to
      45% reduction in incidence-based breast cancer mortality among women actually
      screened. In this article, we apply new analytic methods for the evaluation of
      breast cancer mortality, using all breast cancer deaths in the period under
      study. METHODS: Data were available from 13 areas on breast cancer mortality by
      year of diagnosis, year of death, and screening exposure. The period of study
      varied by area, the overall range of year of diagnosis being 1968 to 2001. We had
      data on 6,231 deaths and an average population of 555,676 women ages 40 to 69
      years. Analysis of the effect of being screened was conducted using an
      alternative statistical analysis applied to all breast cancer deaths in the
      period of study, in addition to the incidence-based mortality analysis in our
      companion article. Data were analyzed using Poisson regression and adjusted for
      self-selection bias, contemporaneous changes in incidence, and changes in
      mortality independent of screening. RESULTS: Using all deaths in the period of
      observation, a significant 42% reduction in breast cancer mortality was observed,
      adjusting for contemporaneous changes independent of screening [relative risk
      (RR), 0.58; 95% confidence interval (95% CI), 0.53-0.62]. After further
      adjustment for self-selection bias, the mortality reduction was 39% (RR, 0.61;
      95% CI, 0.55-0.68), also highly significant. CONCLUSIONS: These results indicate
      a reduction in breast cancer mortality of 39% in association with screening,
      after adjustment for contemporaneous changes and self-selection bias. These
      results confirm previous conclusions arrived at using incidence-based mortality
      analyses.

PMID- 16434587
TI  - Effect of physical activity on women at increased risk of breast cancer: results
      from the E3N cohort study.
AB  - PURPOSE: There is a need to investigate the type, duration, frequency, and
      intensity of physical activity that are critical to reduce the risk of breast
      cancer, and if this relation differs among subgroups of women. METHODS: We
      analyzed the relation between physical activity and breast cancer incidence
      between 1990 and 2002 (n=3,424 cases), among 90,509 women of the French E3N
      cohort, ages between 40 and 65 years in 1990. We gave special attention to effect
      modification by body mass index (BMI), family history of breast cancer, parity,
      and hormone replacement therapy (HRT). RESULTS: A linear decrease in risk of
      breast cancer was observed with increasing amounts of moderate (P(trend)<0.01)
      and vigorous (P(trend)<0.0001) recreational activities. Compared with women who
      reported no recreational activities, those with more than five weekly hours of
      vigorous recreational activity had a relative risk of 0.62 (0.49-0.78). This
      decrease was still observed among women who were overweight, nulliparous, had a
      family history of breast cancer, or used HRT. Compared with the whole cohort,
      among nulliparous women, the reduction of risk observed was of a higher
      magnitude, although the test for heterogeneity did not reach statistical
      significance. CONCLUSION: A risk reduction of breast cancer was particularly
      observed with vigorous recreational activity. Further investigations are needed
      to confirm that intensity is an important variable to consider in risk reduction
      and to identify the precise biological mechanisms involved in such a risk
      reduction.

PMID- 16434588
TI  - Clinical stage of breast cancer by parity, age at birth, and time since birth: a
      progressive effect of pregnancy hormones?
AB  - Breast cancer diagnosed during pregnancy or 1 to 2 years after birth often occurs
      at a late stage. Little is known about tumor characteristics in the high-risk
      period shortly after a childbirth. We here explore whether stage of disease
      differs according to timing of births. Results are based on 22,351 Norwegian
      breast cancer patients of parity 0 to 5, ages 20 to 74 years. The proportion of
      stage II to IV tumors was considerably higher among parous than nulliparous women
      at age <30 years (52.7% versus 36.8%, P=0.009), but similar or lower in other age
      groups (P(interaction)=0.029). In general, the largest proportion of stage II to
      IV tumors was found among women diagnosed during pregnancy or <2 years after
      birth. However, among women with late-age births (first or second birth >or=30
      years, third birth >or=35 years), as well as women with an early second birth
      (<25 years), the proportion with advanced disease was rather similar or even
      higher among those diagnosed 2 to 6 years after birth (49.3-56.0%). The
      association between clinical stage and time since birth reached statistical
      significance among women with a late first or second birth and among all
      triparous women (P <or= 0.032). The subgroups with a high proportion of advanced
      disease 2 to 6 years after birth corresponded quite well to those previously
      found to have the most pronounced transient increase in risk after birth. Thus,
      pregnancy hormones may have a progressive effect on breast cancer tumors in
      addition to a possible promoting effect. A potential effect of prolactin is
      discussed.

PMID- 16434589
TI  - Complementary medicine use before and 1 year following genetic testing for
      BRCA1/2 mutations.
AB  - PURPOSE: We explored change in complementary and alternative medicine (CAM) use
      by unaffected women and cancer survivors from enrollment into a randomized
      BRCA1/2 testing program to CAM use 1 year following results disclosure. METHODS:
      A cohort of 243 high-risk women completed questionnaires at enrollment into a
      BRCA1/2 randomized trial and 1 year post results disclosure. Uses of several CAMs
      for cancer prevention were explored, including ingestible, behavioral, and
      physical modalities. Assessment of the change in CAM use from baseline to 1 year
      follow-up was conducted using a repeated self-administered questionnaire.
      Correlates of the number of CAMs used at 1 year were explored using multivariable
      linear regression models. RESULTS: Among the subset of women who changed their
      CAM behavior from enrollment to 1 year following BRCA1/2 results disclosure,
      there was a significantly higher proportion who changed from no CAM use to CAM
      use among the overall cohort (P=0.01), among women without cancer at enrollment
      (P=0.003), among women found to be BRCA1/2 carriers (P=0.03), and among women
      randomized to the genetic counseling intervention arm of the study (P=0.009).
      Number of CAMs used at 1 year was positively associated with number of CAMs used
      at baseline, sunscreen use, and BRCA1/2 mutation status. CONCLUSION: High-risk
      women who have received BRCA1/2 counseling and testing frequently adopt new CAM
      use in the first year after learning their genetic status. Mutation carriers
      frequently initiate CAM use after learning their genetic status as part of their
      cancer preventive regimen. Further studies are warranted to determine the
      efficacy of CAM-related strategies for cancer prevention.

PMID- 16434590
TI  - The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and
      BRCA2 mutation carriers.
AB  - This is by far the largest study of its kind to date, and further suggests that
      AIB1 does not play a substantial role in modifying the phenotype of BRCA1 and
      BRCA2 carriers. The AIB1 gene encodes the AIB1/SRC-3 steroid hormone receptor
      coactivator, and amplification of the gene and/or protein occurs in breast and
      ovarian tumors. A CAG/CAA repeat length polymorphism encodes a stretch of 17 to
      29 glutamines in the HR-interacting carboxyl-terminal region of the protein which
      is somatically unstable in tumor tissues and cell lines. There is conflicting
      evidence regarding the role of this polymorphism as a modifier of breast cancer
      risk in BRCA1 and BRCA2 carriers. To further evaluate the evidence for an
      association between AIB1 glutamine repeat length and breast cancer risk in BRCA1
      and BRCA2 mutation carriers, we have genotyped this polymorphism in 1,090 BRCA1
      and 661 BRCA2 mutation carriers from Australia, Europe, and North America. There
      was no evidence for an increased risk associated with AIB1 glutamine repeat
      length. Given the large sample size, with more than adequate power to detect
      previously reported effects, we conclude that the AIB1 glutamine repeat does not
      substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

PMID- 16434591
TI  - p53 Mutation analysis in breast tumors by a DNA microarray method.
AB  - The p53 gene acts as a regulator of cell growth and DNA repair in normal cells;
      inactivation of the gene seems to lead to cancer. It is the most commonly mutated
      gene in human cancers, and a high-throughput sequencing method is needed for
      cancer etiology studies using large sample sets. In our population-based case
      control study of breast cancer, the p53 gene was amplified by PCR for 392
      subjects from seven hospitals in Western New York using the Affymetrix GeneChip
      technology. One hundred thirty-eight (35%) of the breast tumors had p53
      mutations, of which 88% were located in exons 5 to 8. New hotspots were
      identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and
      previously reported hotspots were found at codons 175, 248, and 273. Manual
      sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate
      the Affymetrix assay. The two methods had 100% concordance for mutations
      detectable by the Affymetrix assay. We also successfully assayed paraffin
      embedded breast and lung tumors from as early as 1958 and employed a nested PCR
      strategy to improve weak PCR amplification. To have statistical power, the
      investigation of gene environment interactions and cancer requires a large number
      of tumor analyses, which are frequently only available from archived tissue from
      multiple sources. We have shown the utility of the Affymetrix GeneChip method
      under these challenging conditions and provided new data for the mutational
      spectra of breast cancer in a population-based study.

PMID- 16434592
TI  - Circulating steroid hormones and the risk of prostate cancer.
AB  - Epidemiologic studies have failed to support the hypothesis that circulating
      androgens are positively associated with prostate cancer risk and some recent
      studies have even suggested that high testosterone levels might be protective
      particularly against aggressive cancer. We tested this hypothesis by measuring
      total testosterone, androstanediol glucuronide, androstenedione, DHEA sulfate,
      estradiol, and sex hormone-binding globulin in plasma collected at baseline in a
      prospective cohort study of 17,049 men. We used a case-cohort design, including
      524 cases diagnosed during a mean 8.7 years follow-up and a randomly sampled sub
      cohort of 1,859 men. The association between each hormone level and prostate
      cancer risk was tested using Cox models adjusted for country of birth. The risk
      of prostate cancer was approximately 30% lower for a doubling of the
      concentration of estradiol but the evidence was weak (P(trend)=0.07). None of the
      other hormones was associated with overall prostate cancer (P(trend) >or= 0.3).
      None of the hormones was associated with nonaggressive prostate cancer (all
      P(trend) >or= 0.2). The hazard ratio [HR; 95% confidence interval (95% CI)] for
      aggressive cancer almost halved for a doubling of the concentration of
      testosterone (HR, 0.55; 95% CI, 0.32-0.95) and androstenedione (HR, 0.51; 95% CI,
      0.31-0.83), and was 37% lower for a doubling of the concentration of DHEA sulfate
      (HR, 0.63; 95% CI, 0.46-0.87). Similar negative but nonsignificant linear trends
      in risk for aggressive cancer were obtained for free testosterone, estradiol, and
      sex hormone-binding globulin (P(trend)=0.06, 0.2, and 0.1, respectively). High
      levels of testosterone and adrenal androgens are thus associated with reduced
      risk of aggressive prostate cancer but not with nonaggressive disease.

PMID- 16434593
TI  - A prospective study of lycopene and tomato product intake and risk of prostate
      cancer.
AB  - BACKGROUND: Dietary lycopene and tomato products may reduce risk of prostate
      cancer; however, uncertainty remains about this possible association. METHODS: We
      evaluated the association between intake of lycopene and specific tomato products
      and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer
      Screening Trial, a multicenter study designed to investigate cancer early
      detection methods and etiologic determinants. Participants completed both a
      general risk factor and a 137-item food frequency questionnaire at baseline. A
      total of 1,338 cases of prostate cancer were identified among 29,361 men during
      an average of 4.2 years of follow-up. RESULTS: Lycopene intake was not associated
      with prostate cancer risk. Reduced risks were also not found for total tomato
      servings or for most tomato-based foods. Statistically nonsignificant inverse
      associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83;
      95% confidence interval (95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5
      serving/mo; P(trend)=0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56
      1.10; P(trend)=0.12] and spaghetti/tomato sauce consumption (advanced prostate
      cancer: RR=0.81, 95% CI, 0.57-1.16 for >or=2 servings/wk versus<1 serving/mo;
      P(trend)=0.31). Among men with a family history of prostate cancer, risks were
      decreased in relation to increased consumption of lycopene (P(trend)=0.04) and
      specific tomato-based foods commonly eaten with fat (spaghetti, P(trend)=0.12;
      pizza, P(trend)=0.15; lasagna, P(trend)=0.02). CONCLUSIONS: This large study does
      not support the hypothesis that greater lycopene/tomato product consumption
      protects from prostate cancer. Evidence for protective associations in subjects
      with a family history of prostate cancer requires further corroboration.

PMID- 16434595
TI  - Cutting cost and increasing access to colorectal cancer screening: another
      approach to following the guidelines.
AB  - CONTEXT: Through medical decision making, physicians in the U.S. influence the
      spending of >$1.3 trillion or 15% of the gross domestic product. U.S. physicians
      are challenged to identify areas of clinical practice to improve while cutting
      cost and increasing access. Primary screening for colorectal cancer is a good
      example to illustrate this point. OBJECTIVE: To apply a population-based method
      of medical decision making in the area of primary screening for colorectal cancer
      in order to illustrate a reduction in health care costs while increasing access
      and maintaining quality of care. DESIGN: We used a combination of (a) census
      population data, (b) National Cancer Institute Survey data on screening rates,
      and (c) charge data to estimate the current costs of colorectal cancer screening.
      We also estimated cost and capacity increases that would occur under various
      other screening scenarios. These included all currently screened subjects
      receiving annual fecal occult blood testing (FOBT), all currently unscreened
      individuals undergoing either colonoscopy every decade or annual FOBT, and all
      eligible subjects undergoing annual FOBT. MAIN OUTCOME MEASURES: Cost and access
      differences between current screening activity and other potential scenarios
      compliant with guidelines. RESULTS: Screening for colorectal cancer with yearly,
      six-window, rehydrated FOBT for all normal-risk individuals over the age of 50
      has the potential to screen 3,813,095 more Americans for colon cancer yearly than
      are currently being screened, while costing $8.7 billion less per decade than
      what is currently being spent on screening a fraction of the population. Looking
      into the future, it is possible to increase screening rates from 50% to 100%,
      while saving almost $10 billion per decade by using FOBT for all eligible
      Americans. In practice, some proportion of these benefits would be realized as
      the calculations assume a 100% patient compliance rate. CONCLUSIONS: Considering
      a population-based approach and the balance among quality, accessibility, and
      cost parameters, we recommend primary screening for colorectal cancer to be based
      on yearly six-window, rehydrated FOBT. Colonoscopy due to cost and access issues
      should be relegated to secondary screening and case finding.

PMID- 16434594
TI  - Effect of NAT1 and NAT2 genetic polymorphisms on colorectal cancer risk
      associated with exposure to tobacco smoke and meat consumption.
AB  - N-Acetyltransferases 1 and 2 (NAT1 and NAT2), both being highly polymorphic, are
      involved in the metabolism of aromatic and heterocyclic aromatic amines present
      in cigarette smoke and red meat cooked by high-temperature cooking techniques. We
      investigated the effect of differences in acetylation capacity, determined by
      NAT1 and NAT2 genotypes, on colorectal cancer risk associated with exposure to
      tobacco smoke or red meat consumption. In this population-based case-control
      study in Germany, 505 patients with incident colorectal cancer and 604 age- and
      sex-matched control individuals with genotyping data and detailed risk factor
      information were included. Genotyping of NAT1 and NAT2 genetic polymorphisms was
      done using a fluorescence-based melting curve analysis method. The association
      between genotypes, environmental exposures, and colorectal cancer risk was
      estimated using multivariate logistic regression. Colorectal cancer risk
      associated with active smoking was elevated after accumulation of 30(+) pack
      years of smoking [odds ratio (OR), 1.4; 95% confidence interval (95% CI), 0.9
      2.2] but not significantly modified by either NAT1 or NAT2 genotype. Exposure to
      environmental tobacco smoke was associated with an increased risk for colorectal
      cancer only among NAT2 fast acetylators (OR, 2.6; 95% CI, 1.1-5.9 for exposure in
      childhood and adulthood). Frequent consumption of red meat significantly
      increased colorectal cancer risk for the group comprising all NAT2 fast
      acetylators or carriers of the NAT1*10 allele (OR, 2.6; 95% CI, 1.1-6.1) but not
      among those with "slow" NAT1 and NAT2 genotypes. Our findings indicate that NAT1
      and NAT2 genotypes may contribute jointly to individual susceptibility and that
      heterocyclic aromatic amines may play an important role in colorectal cancer
      associated with red meat and possibly also exposure to environmental tobacco
      smoke.

PMID- 16434596
TI  - Discovery of novel methylation biomarkers in cervical carcinoma by global
      demethylation and microarray analysis.
AB  - A genome-wide screening study for identification of hypermethylated genes in
      invasive cervical cancer (ICC) was carried out to augment our previously
      discovered panel of three genes found to be useful for detection of ICC and its
      precursor neoplasia. Putatively hypermethylated and silenced genes were
      reactivated in four ICC cell lines by treatment with 5-aza-2'-deoxycytidine and
      trichostatin A and identified on expression microarrays. Thirty-nine of the 235
      genes up-regulated in multiple ICC cell lines were further examined to determine
      the methylation status of associated CpG islands. The diagnostic use of 23 genes
      that were aberrantly methylated in multiple ICC cell lines were then analyzed in
      DNA from exfoliated cells obtained from patients with or without ICC. We show,
      for the first time, that aberrant methylation of six genes (SPARC, TFPI2, RRAD,
      SFRP1, MT1G, and NMES1) is present in a high proportion of ICC clinical samples
      but not in normal samples. Of these genes, SPARC and TFPI2 showed the highest
      frequency of aberrant methylation in ICC specimens (86.4% for either) and
      together were hypermethylated in all but one ICC cases examined. We conclude that
      expression profiling of epigenetically reactivated genes followed by methylation
      analysis in clinical samples is a powerful tool for comprehensive identification
      of methylation markers. Several novel genes identified in our study may be
      clinically useful for detection or stratification of ICC and/or of its precursor
      lesions and provide a basis for better understanding of mechanisms involved in
      development of ICC.

PMID- 16434597
TI  - Evaluating bias due to population stratification in epidemiologic studies of gene
      gene or gene-environment interactions.
AB  - Confounding by ethnicity (i.e. population stratification) can result in bias and
      incorrect inferences in genotype-disease association studies, but the effect of
      population stratification in gene-gene or gene-environment interaction studies
      has not been addressed. We used logistic regression models to fit multiplicative
      interactions between two dichotomous variables that represented genetic and/or
      environmental factors for a binary disease outcome in a hypothetical cohort of
      multiple ethnicities. Biases in main effects and interactions due to population
      stratification were evaluated by comparing regression coefficients in mis
      specified models that ignored ethnicities with their counterparts in models that
      accounted for ethnicities. We showed that biases in main effects and interactions
      were constrained by the differences in disease risks across the ethnicities.
      Therefore, large biases due to population stratification are not possible when
      baseline disease risk differences among ethnicities are small or moderate.
      Numerical examples of biases in genotype-genotype and/or genotype-environment
      interactions suggested that biases due to population stratification for main
      effects were generally small but could become large for studies of interactions,
      particularly when strong linkage disequilibrium between genes or large
      correlations between genetic and environmental factors existed. However, when
      linkage disequilibrium among genes or correlations among genes and environments
      were small, biases to main effects or interaction odds ratios were small to
      nonexistent.

PMID- 16434598
TI  - How well do HapMap haplotypes identify common haplotypes of genes? A comparison
      with haplotypes of 334 genes resequenced in the environmental genome project.
AB  - One of the goals of the International HapMap Project is the identification of
      common haplotypes in genes. However, HapMap uses an incomplete catalogue of
      single nucleotide polymorphisms (SNPs) and might miss some common haplotypes. We
      examined this issue using data from the Environmental Genome Project (EGP) which
      resequenced 335 genes in 90 people, and thus, has a nearly complete catalogue of
      gene SNPs. The EGP identified a total of 45,243 SNPs, of which 10,780 were common
      SNPs (minor allele frequency >or=0.1). Using EGP common SNP genotype data, we
      identified 1,459 haplotypes with frequency >or=0.05 and we use these as
      "benchmark" haplotypes. HapMap release 16 had genotype information for 1,573 of
      10,780 (15%) EGP common SNPs. Using these SNPs, we identified common HapMap
      haplotypes (frequency >or=0.05) in each of the four HapMap ethnic groups. To
      compare common HapMap haplotypes to EGP benchmark haplotypes, we collapsed
      benchmark haplotypes to the set of 1,573 SNPs. Ninety-eight percent of the
      collapsed benchmark haplotypes could be found as common HapMap haplotypes in one
      or more of the four HapMap ethnic groups. However, collapsing benchmark
      haplotypes to the set of SNPs available in HapMap resulted in a loss of haplotype
      information: 545 of 1,459 (37%) benchmark haplotypes were uniquely identified,
      and only 25% of genes had all their benchmark haplotypes uniquely identified. We
      resampled the EGP data to examine the effect of increasing the number of HapMap
      SNPs to 5 million, and estimate that approximately 40% of common SNPs in genes
      will be sampled and that half of the genes will have sufficient SNPs to identify
      all common haplotypes. This inability to distinguish common haplotypes of genes
      may result in loss of power when examining haplotype-disease association.

PMID- 16434599
TI  - Variation of the N-acetyltransferase 2 gene in a Romanian and a Kyrgyz
      population.
AB  - As part of a project on environmental disasters in minority populations, this
      study aimed to evaluate differences in the sequence of N-acetyltransferase 2
      (NAT2) as a metabolic susceptibility gene in yet unexplored ethnicities. Eight
      single nucleotide polymorphisms (SNP) in the NAT2 coding region and a variant in
      the 3' flanking region were analyzed in 290 unrelated Kyrgyz and 140 unrelated
      Romanians by SNP-specific PCR analysis. The variants 341C, 481T, and 803G were
      less and 857A more prevalent in Kyrgyz (P < 0.0001). The variant at site 857
      indicates Asian descent. 282C>T and 590G>A showed no significant variation by
      ethnicity. 364G>A and 411A>T turned out to be monomorphic. Database comparisons
      of the NAT2 minor allele frequencies support that Romanians belong to Caucasians
      and Kyrgyz are in between Caucasians and East Asians. The distributions of
      predicted haplotypes differed significantly between the two ethnicities where the
      Kyrgyz showed a higher genetic diversity. The haplotype without mutations was
      more common in Kyrgyz (40.1% in Kyrgyz, 29.3% in Romanians). Accordingly, the
      imputed slow acetylator phenotype was less prevalent in Kyrgyz (35.2% versus
      51.4% in Romanians). We found pronounced ethnic differences in NAT2 genotypes
      with yet unknown effect on the health risks for environmental or occupational
      exposures in minority populations.

PMID- 16434600
TI  - Sun-protective behavior among individuals with a family history of melanoma.
AB  - Routine sun protection is recommended to prevent skin cancer. Skin cancer
      prevention may be particularly important for individuals at greater risk, such as
      those with a family history of melanoma. Our aims were to examine the prevalence
      of sun-protective behavior (SPB) in unaffected first-degree relatives (FDR) of
      individuals diagnosed with melanoma and to examine the relationship between
      protection motivation theory (PMT) variables (i.e., perceived risk, perceived
      severity, self-efficacy, response efficacy) and SPB. FDRs (n=100), who were
      nominated by melanoma patients, completed a standardized, self-report
      questionnaire measuring demographic characteristics, melanoma risk factors, PMT
      variables, and SPB. The results indicated that less than one-third of FDRs used
      sunscreen routinely when in the sun and fewer stayed in the shade or used
      protective clothing on a frequent basis. FDRs with a college education and with
      more melanoma risk factors reported higher levels of SPB. Of the four PMT
      variables, greater perceived risk and greater self-efficacy were significantly
      correlated with higher levels of SPB. Furthermore, results of multiple regression
      analyses suggest that perceived risk mediated the relationship between education
      and SPB and between melanoma risk factors and SPB. These findings suggest that
      interventions to increase the frequency of SPB in at-risk individuals should
      highlight risk information as well as methods to improve individuals' confidence
      in their abilities to engage in SPB.

PMID- 16434602
TI  - Intentions to participate in genetics research among African American smokers.
AB  - Although prior studies have shown that African American smokers are likely to
      carry some of the genetic variants associated with smoking risk, additional
      research with African American smokers is needed to replicate these findings.
      Limited information is available on interest in participating in research to
      identify genetic risk factors for smoking among African American smokers;
      therefore, the goals of the present study were to describe intentions to
      participate in smoking and genetics research, and to determine factors that are
      associated with participation intentions. Subjects were 128 African American male
      and female adult smokers. Sociodemographic characteristics, clinical factors,
      attitudes about genetic testing, and intentions to participate in genetics
      research were evaluated during a structured telephone interview. Overall, 58% of
      respondents reported that they would be very likely to participate in research to
      identify genetic risk factors for smoking. Greater beliefs about the benefits of
      participating in medical research (odds ratio, 3.17; 95% confidence interval,
      1.45-6.94; P = 0.004) and fewer perceptions of the limitations and risks of
      genetic testing (odds ratio, 0.90; 95% confidence interval, 0.82-0.98; P = 0.01)
      had significant independent associations with reporting a high likelihood of
      participating in this type of research. Recruitment messages and protocols that
      address the benefits of research participation, as well as concerns about the
      limitations and risks of genetic testing, may enhance African American
      participation in research on genetics and smoking.

PMID- 16434601
TI  - Eliminating carcinogenic acetaldehyde by cysteine from saliva during smoking.
AB  - Tobacco smoking is one of the strongest risk factors not only for lung cancer but
      also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown
      to dissolve into the saliva during smoking and to be a local carcinogen in the
      human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its
      toxicity. We developed a tablet that releases cysteine into the oral cavity
      during smoking and could therefore be a potential chemopreventive agent against
      toxicity of tobacco smoke. In this study, the efficacy of l-cysteine-containing
      tablets to reduce the carcinogenic acetaldehyde in the saliva during tobacco
      smoking was examined. Seven volunteers smoked five cigarettes. During every
      smoking period, each volunteer sucked a blinded tablet containing 0, 1.25, 2.5,
      5, or 10 mg of l-cysteine. Acetaldehyde was analyzed from salivary samples gas
      chromatographically at 0, 5, and 10 minutes from the beginning of the smoking.
      All tablets containing l-cysteine reduced highly significantly the salivary
      acetaldehyde; 5 mg of l-cysteine was the minimum concentration to totally
      eliminate the acetaldehyde from saliva. The mean salivary acetaldehyde
      concentrations in samples collected immediately after smoking with 0, 1.25, 2.5,
      5, or 10 mg of l-cysteine were 228+/-115 micromol/L, 85+/-42 micromol/L
      (P=0.007), 9+/-7 micromol/L, 0.09+/- 0.2 micromol/L, 0+/- 0 micromol/L (P<0.001),
      respectively. In conclusion, carcinogenic acetaldehyde could be totally
      inactivated in the saliva during smoking by sucking tablet containing 5 mg of l
      cysteine. Even a small reduction of the carcinogenicity of cigarette smoke could
      gain benefit at the population level. Hence, this finding warrants for further
      clinical trials for l-cysteine tablet in the prevention of upper digestive tract
      cancers in smokers.

PMID- 16434603
TI  - Smoking rates and topography predict adolescent smoking cessation following
      treatment with nicotine replacement therapy.
AB  - Establishing measurement invariance of tobacco addiction among adolescents
      remains challenging. In adult smoking cessation trials, poor outcome is predicted
      by high cigarette consumption and large puff volume at baseline. We examined the
      predictive value of pretreatment smoking rates and topography variables for
      abstinence outcomes among 66 adolescents enrolled in a 3-month smoking cessation
      trial using nicotine replacement and cognitive behavioral therapy. Pretreatment
      variables included cigarettes per day (CPD), puff volume, puff duration, and
      several youth-adapted Fagerstrom-derived questionnaire scores. Outcome measures
      included prolonged abstinence at end of treatment and point-prevalent abstinence
      3 months after the end of the trial. Logistic regression controlling for
      treatment group showed that increases in baseline CPD (odds ratio, 1.438; 95%
      confidence interval, 1.051-1.967) and average puff volume (odds ratio, 1.168; 95%
      confidence interval, 1.030-1.326) predicted continued smoking at the end of
      treatment. Puff volume (P=0.013), but not CPD, predicted abstinence at the 3
      month follow-up. None of the youth-adapted Fagerstrom questionnaires predicted
      outcome on either abstinence measure. If confirmed in a larger sample, our
      findings suggest that puff topography, and possibly CPD, might predict cessation
      outcome better than Fagerstrom scores in adolescent smokers.

PMID- 16434604
TI  - Combined effects of the p53 and p73 polymorphisms on lung cancer risk.
AB  - Lung cancer is a multigenic disease where one variant single nucleotide
      polymorphism may have only a modest independent effect on the disease phenotype,
      yet in aggregate, multiple biologically relevant single nucleotide polymorphisms
      may provide a more accurate representation of risk. Polymorphisms in members of
      the p53 family, such as p53 and p73, that have a functional relevance would be
      predicted to contribute to the disease phenotype. In this analysis, we used
      genotype data from 863 lung cancer cases and 852 healthy controls to test for
      multigenetic effects of polymorphisms at p53 exon 4, introns 3 and 6, and at p73
      exon 2. All individuals in this analysis were self-reported non-Hispanic
      Caucasians. When the p73 and p53 variant alleles were combined and analyzed as a
      continuous variable, there was a 13% increase [odds ratios (OR), 1.13; 95%
      confidence intervals (CI), 1.05-1.21] in lung cancer risk for each additional
      variant allele. Furthermore, when the number of variant alleles was categorized
      into three groups (zero, one to three, and four or more variants), there was
      evidence of a gene-dosage effect with increased risks for individuals with one to
      three variants (OR, 1.30; 95% CI, 1.05-1.61) and four or more variants (OR, 1.78;
      95% CI, 1.23-2.56). When the data were stratified by smoking status, an increased
      risk for lung cancer was evident only in current (OR, 2.32; 95% CI, 1.25-4.33)
      and former smokers (OR, 1.73; 95% CI, 1.02-2.94) with four or more variants.
      Younger individuals with four or more variants were also at a significantly
      increased risk for lung cancer (OR, 3.15; 95% CI, 1.62-6.12). This study provides
      support for the multigenetic effects of variant alleles from p53 exon 4, and
      introns 3 and 6, and p73, and their interplay with smoking, resulting in a
      significantly increased risk for lung cancer in this Caucasian population.

PMID- 16434605
TI  - Breast cancer risk reduction options: awareness, discussion, and use among women
      from four ethnic groups.
AB  - BACKGROUND: With recent advances in breast cancer risk reduction practices, it is
      increasingly important to assess both the breadth of and disparities in use
      across different racial/ethnic groups. METHODS: We conducted telephone interviews
      with 1,700 women ages 40 to 74, from four racial/ethnic groups, without prior
      history of breast cancer, who received mammograms at one of five mammography
      facilities in San Francisco. Main outcomes measured included recognition of
      tamoxifen, raloxifene, genetic testing, and prophylactic surgery. Global
      indicators (recognition of any therapy, discussion of breast cancer risk) were
      developed from original outcome measures and analyzed using logistic regression.
      RESULTS: Multivariate analyses indicate that race/ethnicity and interview
      language affected recognition of therapies and discussion of risk. White women
      were more likely than all other women to recognize any therapy and more likely
      than Asian-Americans to discuss risk. Women at high risk, who had a prior
      abnormal mammogram, who perceived themselves to be at high risk, or who were
      exposed to breast health information were more likely to discuss risk.
      CONCLUSIONS: Women are aware of preventive therapies, although discussion and use
      is limited. Interventions to increase use of therapies should focus on those at
      high risk.

PMID- 16434606
TI  - Dietary patterns and risk of prostate cancer in U.S. men.
AB  - We prospectively investigated the associations between dietary patterns and risk
      of prostate cancer in the Health Professionals Follow-up Study. Between 1986 and
      2000, 3,002 incident prostate cancer cases were identified in our cohort. Using
      factor analysis, two major dietary patterns were identified, a prudent and a
      western dietary pattern. Dietary patterns were not appreciably associated with
      risk of total prostate cancer. For the highest versus the lowest quintiles, the
      multivariable relative risk (RR) for the prudent pattern was 0.94 [95% confidence
      interval (CI), 0.83-1.06], and for the western pattern, the multivariable RR was
      1.03 (95% CI, 0.92-1.17). Neither were these associated with risk of advanced
      prostate cancer [highest versus lowest quintile, prudent pattern (RR, 1.01; 95%
      CI, 0.68-1.49); western pattern (RR, 1.13; 95% CI, 0.77-1.67)]. Higher western
      pattern scores were suggestively associated with a greater risk of advanced
      prostate cancer among older men [highest versus lowest quintile (RR, 1.35; 95%
      CI, 0.97-1.90)], but not after adding processed meat to the model [highest versus
      lowest quintile (RR, 1.11; 95% CI, 0.75-1.65)]. We did not find any evidence for
      a protective association between prudent pattern and risk of prostate cancer. The
      lack of association between a western dietary pattern as identified by factor
      analysis in our cohort and prostate cancer risk suggests that dietary risk
      factors for prostate cancer are likely to differ from those for other conditions,
      such as cardiovascular disease and type 2 diabetes, that have been associated
      with a western dietary pattern in this cohort.

PMID- 16434607
TI  - Igf-I genetic variation and breast cancer: the multiethnic cohort.

PMID- 16434608
TI  - No association between the MDM2 -309 T/G promoter polymorphism and breast cancer
      in African-Americans or Whites.

PMID- 16434609
TI  - Polymorphisms in the ICAM gene locus are not associated with breast cancer Risk.

PMID- 16434612
TI  - Expanded publishing model for genetic association studies.

PMID- 16434610
TI  - No evidence for large-scale germline genomic aberrations in hereditary bladder
      cancer patients with high-resolution array-based comparative genomic
      hybridization.

PMID- 16434613
TI  - Journals should publish all "null" results and should sparingly publish
      "positive" results.

PMID- 16434614
TI  - Implication of the phosphatidylinositol-3 kinase/protein kinase B signaling
      pathway in the neuroprotective effect of estradiol in the striatum of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine mice.
AB  - The present experiments sought to determine the implication of estrogen receptors
      (ERalpha and ERbeta) and their interaction with insulin-like growth factor
      receptor (IGF-IR) signaling pathways in neuroprotection by estradiol against 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. C57BL/6 male mice
      were pretreated for 5 days with 17beta-estradiol, an estrogen receptor alpha
      (ERalpha) agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol
      (PPT), or an estrogen receptor beta (ERbeta) agonist, 5-androsten-3beta, 17beta
      diol (Delta5-diol). On day 5, mice received MPTP (9 mg/kg) or saline injections,
      and estrogenic treatments were continued for 5 more days. MPTP decreased striatal
      dopamine, measured by high-performance liquid chromatography, to 59% of control
      values; 17beta-estradiol and PPT but not Delta5-diol protected against this
      depletion. MPTP increased IGF-IR measured by Western blot, which was prevented by
      PPT. The phosphorylation of protein kinase B (Akt) (at serine 473), an essential
      mediator of IGF-I neuroprotective actions, increased after 17beta-estradiol and
      tended to increase with PPT but not with Delta5-diol treatments in MPTP mice.
      Glycogen synthase kinase 3beta (GSK3beta) phosphorylation (at serine 9) was
      greatly reduced in MPTP mice; this was completely prevented by PPT, whereas
      17beta-estradiol and Delta5-diol treatments were less effective. The ratio
      between the levels of striatal Bcl-2 and BAD proteins, two apoptotic regulators,
      decreased after MPTP treatment. This effect was effectively prevented only in the
      animals treated with PPT. In nonlesioned mice, 17beta-estradiol and PPT increased
      phosphorylation of striatal Akt and GSK3beta, whereas the other markers measured
      remained unchanged. Delta5-Diol increased GSK3beta phosphorylation less than the
      PPT treatment. These results suggest that a pretreatment with estradiol promoted
      dopamine neuron survival by activating ERalpha and increasing Akt and GSK3beta
      phosphorylation.

PMID- 16434615
TI  - Dissection of an allosteric mechanism on the serotonin transporter: a cross
      species study.
AB  - The serotonin transporter (SERT), which belongs to a family of sodium/chloride
      dependent transporters, is the major pharmacological target in the treatment of
      several clinical disorders, including depression and anxiety. Interaction with a
      low-affinity allosteric site on SERT modulates the ligand affinity at the high
      affinity binding site. Serotonin (5-hydroxytryptamine) and certain SERT
      inhibitors possess affinity for both sites. In the present study, we report the
      characterization of a severely attenuated allosteric mechanism at the recently
      cloned chicken serotonin transporter (gSERT). A cross-species chimera study was
      performed, followed by species scanning mutagenesis. Residues important for the
      allosteric mechanism were mapped to the C-terminal part of SERT containing the
      transmembrane domains 10 to 12. We identified nine residues located in four
      distinct amino acid segments. The contribution of each segment and individual
      residues was investigated. Consequently, a gSERT mutant with a restored
      allosteric mechanism, as well as a human SERT (hSERT) mutant with a severely
      attenuated allosteric mechanism, was generated. The nine residues confer a
      functional allosteric mechanism for different combinations of ligands, suggesting
      that they contribute to a general allosteric mechanism at SERT. The finding of an
      allosteric mechanism at SERT is likely to be of physiological importance, in that
      serotonin was also found to act as an allosteric effector at duloxetine, RTI-55
      and (S)-citalopram. Furthermore, the allosteric potency of 5-HT was found to be
      conserved for both hSERT and gSERT.

PMID- 16434616
TI  - Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid
      receptor gene in Jurkat T cells.
AB  - Opioids and cannabinoids are both associated with analgetic, psychotropic, and
      immunomodulatory effects. It has been suggested that both systems interact on
      multiple levels. We hypothesized that cannabinoids induce opioid receptors and
      investigated cannabinoid-dependent expression of the mu-opioid receptor subtype
      in a human T cell model. We report that activation of the peripheral cannabinoid
      receptor type 2 leads to a de novo induction of mu-opioid receptor transcription
      in Jurkat E6.1 cells. We show that interleukin-4 is transcriptionally induced in
      response to cannabinoids and that an interleukin-4 receptor antagonist blocks
      cannabinoid-dependent induction of mu-opioid receptors, indicating that induced
      expression of interleukin-4 is required in this process. Induction of interleukin
      4 is blocked by decoy oligonucleotides directed against STAT5, indicating the
      requirement of this transcription factor. In addition, we show cannabinoid
      dependent phosphorylation of STAT5. Further experiments demonstrate that
      interleukin-4 then induces phosphorylation of STAT6, which directly
      transactivates the mu-opioid receptor gene. In addition, STAT6 induces expression
      of the transcription factor GATA3, which also contributes to mu-opioid receptor
      gene transcription. The responsive promoter region of the human mu-opioid
      receptor gene with the binding sites for both factors was mapped to nt -1001 to 
      950. To demonstrate functional mu-opioid receptor proteins, morphine-mediated
      phosphorylation of mitogen-activated protein kinase was investigated. We show
      that phosphorylation of mitogen-activated protein kinase occurs only in
      cannabinoid-prestimulated Jurkat E6.1 cells and that it is blocked by the mu
      opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. In summary,
      these findings provide a first example for cannabinoid-opioid-interactions in
      cells of the immune system.

PMID- 16434617
TI  - Merbarone induces activation of caspase-activated DNase and excision of
      chromosomal DNA loops from the nuclear matrix.
AB  - Studies were carried out to address possible cellular mechanisms by which
      merbarone, a catalytic inhibitor of DNA topoisomerase II, can block tumor cell
      growth without inducing extensive DNA cleavage. Merbarone induced the release of
      high molecular weight DNA fragments from the nuclear matrix of HL-60 leukemia
      cells, which preceded the internucleosomalsize DNA fragmentation characteristic
      of late-stage apoptosis. The chromatin fragments were enriched in a matrix
      attachment region (MAR) sequence compared with a non-MAR sequence and were
      similar in size to DNA loops extracted from nuclear matrices. However, merbarone
      did not directly induce the excision of high molecular weight DNA fragments from
      the nuclear matrix by promoting topoisomerase II-catalyzed DNA cleavage, because
      the drug inhibited topoisomerase II-mediated cleavage in isolated nuclear matrix
      preparations. Instead, merbarone induced rapid activation of the mitochondrial
      apoptosis pathway, which included the following temporal sequence of events:
      dissipation of the mitochondrial transmembrane potential within 30 min, release
      of mitochondrial cytochrome c, and activation of caspase-activated DNase (CAD) by
      its inhibitor ICAD. The excision of high molecular weight DNA was inhibited at
      least 80% in merbarone-treated cells preincubated with the pan-caspase inhibitor
      z-VAD-fmk [Z-Val-Ala-Asp(OMe)-fluoromethyl ketone] and in caspase-resistant
      Jurkat cells (ICAD/double-mutated) that express a mutant form of ICAD. These
      results provide evidence that merbarone can induce rapid disorganization of DNA
      in tumor cells that have a functional mitochondrial apoptosis pathway without
      inducing extensive DNA cleavage.

PMID- 16434618
TI  - Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone
      via glutathione-dependent drug efflux.
AB  - Based upon several previous reports, no consistent relationship between multidrug
      resistance protein 1 (MRP1, ABCC1) expression and cellular sensitivity to
      mitoxantrone (MX) toxicity can be ascertained; thus, the role of MRP1 in MX
      resistance remains controversial. The present study, using paired parental, MRP1
      poor, and transduced MRP1-overexpressing MCF7 cells, unequivocally demonstrates
      that MRP1 confers resistance to MX cytotoxicity and that resistance is associated
      with reduced cellular accumulation of MX. This MRP1-associated reduced
      accumulation of MX was partially reversed by treatment of cells with 50 microM
      MK571 [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2
      dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid]-an MRP inhibitor
      that increased MX accumulation in MRP1-expressing MCF7 cells but had no effect on
      MRP-poor MCF7 cells. Moreover, in vitro experiments using inside-out membrane
      vesicles show that MRP1 supports ATP-dependent, osmotically sensitive uptake of
      MX. Unlike ABCG2 (breast cancer resistance protein, mitoxantrone-resistant
      protein), MRP1-mediated MX transport is dependent upon the presence of
      glutathione or its S-methyl analog. In addition, MX stimulates transport of
      [3H]glutathione. Together, these data are consistent with the interpretation that
      MX efflux by MRP1 involves cotransport of MX and glutathione. The results suggest
      that MRP1-like the alternative MX transporters ABCG2 and ABCB1 (MDR1, P
      glycoprotein)-can significantly influence tumor cell sensitivity to and
      pharmacological disposition of MX.

PMID- 16434619
TI  - The cover. The White Way.

PMID- 16434620
TI  - A piece of my mind. Jigsaw.

PMID- 16434621
TI  - Looking beyond imatinib: next line of targeted drugs for CML shows promise.

PMID- 16434622
TI  - Art from the heart.

PMID- 16434623
TI  - Leading causes of death in the United States.

PMID- 16434624
TI  - Leading causes of death in the United States.

PMID- 16434625
TI  - Race and genetic influences on health.

PMID- 16434626
TI  - A woman with fetal loss.

PMID- 16434627
TI  - A woman with fetal loss.

PMID- 16434628
TI  - Use of breast reconstruction after mastectomy following the Women's Health and
      Cancer Rights Act.

PMID- 16434629
TI  - Frequency and effect of adjuvant radiation therapy among women with stage I
      endometrial adenocarcinoma.
AB  - CONTEXT: The benefit of adjuvant radiation therapy (RT) in stage I endometrial
      adenocarcinoma remains controversial despite several phase 3 trials. OBJECTIVE:
      To evaluate the frequency and effect of adjuvant RT on overall and relative
      survival within a large US population database. DESIGN, SETTING, AND POPULATION:
      A retrospective analysis that used data from the Surveillance, Epidemiology, and
      End Results program of the US National Cancer Institute from January 1, 1988, to
      December 31, 2001. A total of 21,249 patients with American Joint Committee on
      Cancer stage IA-C node-negative endometrial adenocarcinoma comprised the study
      population. MAIN OUTCOME MEASURES: Overall survival curves were constructed using
      Kaplan-Meier method and compared via stratified log-rank test within T
      stage/grade combinations, adjusted for age. Relative survival was performed to
      assess the effects of age, race, stage, grade, whether nodes were examined, and
      whether adjuvant RT was administered. RESULTS: Of 21,249 women, 4080 received
      adjuvant RT (19.2%) and 17,169 did not receive adjuvant RT (80.8%). The mean age
      at diagnosis was 63.2 years (range, 14-99 years). Adjuvant RT significantly
      improved overall survival for patients with stage IC/grade 1 (P<.001) and stage
      IC/grades 3 and 4 (P<.001). Cox proportional hazards regression analysis revealed
      a statistically detectable association of adjuvant RT with improved relative
      survival in patients with stage IC/grade 1 and stage IC/grades 3 and 4 (hazard
      ratio [HR], 0.44; 95% confidence interval [CI], 0.31-0.63; P<.001; and HR, 0.72;
      95% CI, 0.57-0.92; P = .009; respectively). A separate analysis of those patients
      with a surgical lymph node examination at the time of total abdominal
      hysterectomy and bilateral salpingo-oophorectomy revealed similar estimates (HR,
      0.59; 95% CI, 0.39-0.90; P = .01; and HR, 0.73; 95% CI, 0.55-0.96; P = .02;
      respectively). CONCLUSIONS: As the largest reported population analysis to date
      of adjuvant RT in early stage endometrial adenocarcinoma, our study reveals a
      statistically significant association between improved overall and relative
      survival and adjuvant RT in stage IC disease (grades 1 and 3-4). Future work is
      needed to continue to delineate clinical and biological factors, which can guide
      treatment decisions and account for disparities in outcome between varied subsets
      of patients.

PMID- 16434630
TI  - Myocardial injury and long-term mortality following moderate to severe carbon
      monoxide poisoning.
AB  - CONTEXT: Carbon monoxide (CO) poisoning is a common cause of toxicological
      morbidity and mortality. Myocardial injury is a frequent consequence of moderate
      to severe CO poisoning. While the in-hospital mortality for these patients is
      low, the long-term outcome of myocardial injury in this setting is unknown.
      OBJECTIVE: To determine the association between myocardial injury and long-term
      mortality in patients following moderate to severe CO poisoning. DESIGN, SETTING,
      AND PARTICIPANTS: Prospective cohort study of 230 consecutive adult patients
      treated for moderate to severe CO poisoning with hyperbaric oxygen and admitted
      to the Hennepin County Medical Center, a regional center for treatment of CO
      poisoning, between January 1, 1994, and January 1, 2002. Follow-up was through
      November 11, 2005. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Myocardial
      injury (cardiac troponin I level > or =0.7 ng/mL or creatine kinase-MB level > or
      =5.0 ng/mL and/or diagnostic electrocardiogram changes) occurred in 85 (37%) of
      230 patients. At a median follow-up of 7.6 years (range: in-hospital only to 11.8
      years), there were 54 deaths (24%). Twelve of those deaths (5%) occurred in the
      hospital as a result of a combination of burn injury and anoxic brain injury (n =
      8) or cardiac arrest and anoxic brain injury (n = 4). Among the 85 patients who
      sustained myocardial injury from CO poisoning, 32 (38%) eventually died compared
      with 22 (15%) of 145 patients who did not sustain myocardial injury (adjusted
      hazard ratio, 2.1; 95% confidence interval, 1.2-3.7; P = .009). CONCLUSION:
      Myocardial injury occurs frequently in patients hospitalized for moderate to
      severe CO poisoning and is a significant predictor of mortality.

PMID- 16434631
TI  - Effects of omega-3 fatty acids on cancer risk: a systematic review.
AB  - CONTEXT: Omega-3 fatty acids are purported to reduce the risk of cancer. Studies
      have reported mixed results. OBJECTIVE: To synthesize published and unpublished
      evidence to determine estimates of the effect of omega-3 fatty acids on cancer
      risk in prospective cohort studies. DATA SOURCES: Articles published from 1966 to
      October 2005 identified through MEDLINE, PREMEDLINE, EMBASE, Cochrane Central
      Register of Controlled Trials, and CAB Health; unpublished literature sought
      through letters to experts in the neutraceutical industry. STUDY SELECTION: A
      total of 38 articles with a description of effects of consumption of omega-3
      fatty acids on tumor incidence, prospective cohort study design, human study
      population; and description of effect of omega-3 among groups with different
      levels of exposure in the cohort were included. Two reviewers independently
      reviewed articles using structured abstraction forms; disagreements were resolved
      by consensus. DATA EXTRACTION: Two reviewers independently abstracted detailed
      data about the incidence of cancer, the type of cancer, the number and
      characteristics of the patients, details on the exposure to omega-3 fatty acids,
      and the elapsed time between the intervention and outcome measurements. Data
      about the methodological quality of the study were also abstracted. DATA
      SYNTHESIS: Across 20 cohorts from 7 countries for 11 different types of cancer
      and using up to 6 different ways to categorize omega-3 fatty acid consumption, 65
      estimates of the association between omega-3 fatty acid consumption were
      reported. Among these, only 8 were statistically significant. The high degree of
      heterogeneity across these studies precluded pooling of data. For breast cancer 1
      significant estimate was for increased risk (incidence risk ratio [IRR], 1.47;
      95% confidence interval [CI], 1.10-1.98) and 3 were for decreased risk (RR, 0.68
      0.72); 7 other estimates did not show a significant association. For colorectal
      cancer, there was 1 estimate of decreased risk (RR, 0.49; 95% CI, 0.27-0.89) and
      17 estimates without association. For lung cancer one of the significant
      associations was for increased cancer risk (IRR, 3.0; 95% CI, 1.2-7.3), the other
      was for decreased risk (RR, 0.32; 95% CI, 0.13-0.76), and 4 other estimates were
      not significant. For prostate cancer, there was 1 estimate of decreased risk (RR,
      0.43; 95% CI, 0.22-0.83) and 1 of increased risk (RR, 1.98; 95% CI, 1.34-2.93)
      for advanced prostate cancer; 15 other estimates did not show a significant
      association. The study that assessed skin cancer found an increased risk (RR,
      1.13; 95% CI, 1.01-1.27). No significant associations between omega-3 fatty acid
      consumption and cancer incidence were found for aerodigestive cancer, bladder
      cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer.
      CONCLUSIONS: A large body of literature spanning numerous cohorts from many
      countries and with different demographic characteristics does not provide
      evidence to suggest a significant association between omega-3 fatty acids and
      cancer incidence. Dietary supplementation with omega-3 fatty acids is unlikely to
      prevent cancer.

PMID- 16434632
TI  - Does this patient have hearing impairment?
AB  - CONTEXT: Hearing impairment is prevalent among the elderly population but
      commonly underdiagnosed. OBJECTIVE: To review the accuracy and precision of
      bedside clinical maneuvers for diagnosing hearing impairment. DATA SOURCES:
      MEDLINE and EMBASE databases (1966 to April 2005) were searched for English
      language articles related to screening for hearing impairment. STUDY SELECTION:
      Original studies on the accuracy or precision of screening questions and tests
      were included. Articles that used unaccepted reference standards or contained
      insufficient data were excluded. Medical Subject Headings or keywords used in the
      search included hearing loss, hearing handicap, hearing tests, tuning fork,
      deafness, physical examination, sensitivity, specificity, audiometry, tuning fork
      tests, Rinne, Weber, audioscope, Hearing Handicap Inventory for the Elderly
      Screening version, whispered voice test, sensorineural, and conductive. DATA
      EXTRACTION: One author screened all potential articles and 2 authors
      independently abstracted data. Differences were resolved by consensus. Each
      included study (n = 24) was assigned a methodological grade. DATA SYNTHESIS: A
      yes response when asking individuals whether they have hearing impairment has a
      summary likelihood ratio (LR) of 2.5 (95% confidence interval [CI], 1.7-3.6); a
      no response has an LR of 0.13 (95% CI, 0.09-0.19). A score of 8 or greater on the
      screening version of the Hearing Handicap Inventory for the Elderly (HHIE-S) has
      an LR of 3.8 (95% CI, 3.0-4.8); a score less than 8 has an LR of 0.38 (95% CI,
      0.29-0.51). An abnormal Weber tuning fork test response has an LR of 1.6 (95% CI,
      1.0-2.3); a normal response has an LR of 0.70 (95% CI, 0.48-1.0). An abnormal
      Rinne tuning fork test response has LRs ranging from 2.7 to 62; a normal response
      has LRs from 0.01 to 0.85. Inability to perceive a whispered voice has an LR of
      6.1 (95% CI, 4.5-8.4); normal perception has an LR of 0.03 (95% CI, 0-0.24). Not
      passing the audioscope test has an LR of 2.4 (95% CI, 1.4-4.1); passing has an LR
      of 0.07 (95% CI, 0.03-0.17). CONCLUSIONS: Elderly individuals who acknowledge
      they have hearing impairment require audiometry, while those who reply no should
      be screened with the whispered-voice test. Individuals who perceive the whispered
      voice require no further testing, while those unable to perceive the voice
      require audiometry. The Weber and Rinne tests should not be used for general
      screening.

PMID- 16434633
TI  - Health industry practices that create conflicts of interest: a policy proposal
      for academic medical centers.
AB  - Conflicts of interest between physicians' commitment to patient care and the
      desire of pharmaceutical companies and their representatives to sell their
      products pose challenges to the principles of medical professionalism. These
      conflicts occur when physicians have motives or are in situations for which
      reasonable observers could conclude that the moral requirements of the
      physician's roles are or will be compromised. Although physician groups, the
      manufacturers, and the federal government have instituted self-regulation of
      marketing, research in the psychology and social science of gift receipt and
      giving indicates that current controls will not satisfactorily protect the
      interests of patients. More stringent regulation is necessary, including the
      elimination or modification of common practices related to small gifts,
      pharmaceutical samples, continuing medical education, funds for physician travel,
      speakers bureaus, ghostwriting, and consulting and research contracts. We propose
      a policy under which academic medical centers would take the lead in eliminating
      the conflicts of interest that still characterize the relationship between
      physicians and the health care industry.

PMID- 16434634
TI  - Biomedical patents and the public's health: is there a role for eminent domain?

PMID- 16434642
TI  - JAMA patient page. Audiometry.

PMID- 16434635
TI  - US health policy in the aftermath of Hurricane Katrina.

PMID- 16434643
TI  - Unilateral asterixis after thalamic hemorrhage.

PMID- 16434644
TI  - Patient page. Who will make medical decisions for you if you can't make them
      yourself?

PMID- 16434645
TI  - Adolescents get as well as they give: population perspectives on chronic daily
      headaches.

PMID- 16434646
TI  - Primum non nocere: antithombotics after intracerebral hemorrhage?

PMID- 16434647
TI  - Cerebral microbleeds on MRI: prevalence, associations, and potential clinical
      implications.
AB  - OBJECTIVE: To assess the potential role of cerebral microbleeds (CMB) in
      intracerebral hemorrhage (ICH), as indicators of cerebral small-vessel disease,
      and their possible implications for antithrombotic treatment. METHODS: The author
      reviewed literature published through July 2005 from electronic MEDLINE, PubMed,
      and hand searches. CMB prevalence analyses were performed for subjects without
      cerebrovascular disease, with ICH, and with ischemic cerebrovascular disease.
      RESULTS: Prevalence data from more than 5,200 subjects were analyzed. In elderly
      subjects without cerebrovascular disease, CMB prevalence is between 5% and 6%,
      associated with advanced age, while data are inconsistent with regard to CMB and
      chronic hypertension. CMB are prevalent in 68% of patients with spontaneous ICH
      and 40% of those with ischemic cerebrovascular disease. Cerebral microangiopathy
      (lacunes, leukoaraiosis) is associated with the highest prevalence (57%) of CMB
      among patients with ischemic stroke. In patients with suspected cerebral amyloid
      angiopathy (CAA) or Alzheimer disease, CMB are predominantly located in the
      cortical-subcortical area. Current data provide no evidence that CMB increase the
      risk of ICH among patients on antithrombotic treatment or those treated with
      thrombolysis for acute stroke. CONCLUSIONS: Cerebral microbleeds might indicate a
      higher risk of future intracerebral hemorrhage and may be a marker of cerebral
      small-vessel disease and cerebral amyloid angiopathy. However, more prospective
      data are required in order to confirm these assumptions. Recommendations to guide
      antithrombotic treatment based on the detection of cerebral microbleeds are
      presently not justified.

PMID- 16434648
TI  - Disability progression in multiple sclerosis is slower than previously reported.
AB  - OBJECTIVE: To investigate disease progression and risk factors in a large
      geographically based population with multiple sclerosis (MS), using two different
      inception points--clinical onset and date of birth. METHODS: The authors reviewed
      a database of subjects with definite MS and symptom onset prior to July 1988. The
      main outcome was sustained progression to Expanded Disability Status Scale (EDSS)
      6 (requires a cane), using the date of birth and date of MS onset as inception
      points in separate analyses. Risk factors examined were sex, relapsing vs primary
      progressive course, onset age, and onset symptoms. RESULTS: The study included
      2,837 patients, followed prospectively for 22,723 patient years. The median time
      to EDSS 6 was 27.9 years, 15 years after onset; only 21% reached EDSS 6, and by
      age 50, 28% required a cane. Men progressed 38% more quickly than women from
      onset (p < 0.0005), yet both required canes at similar ages: 58.8 years for men
      and 60.1 for women (p = 0.082). A younger onset age predicted a slower
      progression, but those older at onset were consistently older when reaching EDSS
      6. A primary progressive course predicted a more rapid progression from both
      onset (p < 0.0005) and birth (hazard ratio = 2.7 [95% CI: 2.2 to 3.3]). No onset
      symptom consistently predicted progression. CONCLUSION: Disability progression in
      multiple sclerosis (MS) accrued more slowly than found in earlier longitudinal
      studies. The authors also challenged two fundamental concepts in MS,
      demonstrating that neither male sex nor older onset age was associated with worse
      disease outcome.

PMID- 16434649
TI  - Virtual reality cues for improvement of gait in patients with multiple sclerosis.
AB  - OBJECTIVE: To study the effects of visual cues, provided through a portable
      visual-feedback virtual reality (VR) apparatus, on the walking abilities of
      patients with multiple sclerosis (MS). METHODS: On-line (display-on) and residual
      short-term therapeutic effects on walking speed and stride length were measured
      in 16 randomly selected patients with gait disturbances predominantly due to
      cerebellar ataxia. RESULTS: Patients whose baseline walking speed (BWS) was below
      the median showed an average on-line improvement of 13.46% in their walking
      speed, while patients whose BWS was above the median improved their speed by
      1.47%. The average short-term residual therapeutic improvement in walking speed
      was 24.49% in patients with BWS below the median, and 9.09% in patients with BWS
      above the median. Similar results were obtained for improvements in stride
      length. These results of improved functions in patients are particularly
      noteworthy when compared with the lack of change in healthy control subjects.
      CONCLUSIONS: Patients with multiple sclerosis showed improvement in walking
      abilities using virtual reality visual-feedback cues.

PMID- 16434650
TI  - A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County,
      Norway.
AB  - OBJECTIVE: To assess longitudinal follow-up of the incidence of multiple
      sclerosis (MS) through five decades and estimate the prevalence rate in Hordaland
      County, Norway, on January 1, 2003. METHODS: All patients with MS diagnosed from
      1953 to 2003 were identified in the patient records of the Department of
      Neurology, Haukeland University Hospital, Bergen, Norway. The diagnostic criteria
      of Poser et al. were applied and only patients with definite and probable MS were
      included. The study comprises 912 patients, and 666 patients with MS were living
      in Hordaland on January 1, 2003. The annual incidence rates for the years 1953 to
      2003 were calculated. RESULTS: The total crude prevalence rate on January 1,
      2003, was 150.8 per 100,000 population: 191.3 per 100,000 among women and 109.8
      per 100,000 among men. The annual incidence of MS increased from 1.8 per 100,000
      in 1953 to 1957 to 6.0 per 100,000 in 1993 to 1997. CONCLUSIONS: Hordaland
      County, Norway, has changed from a low-risk to a high-risk area for multiple
      sclerosis (MS) during the last 50 years. During the last 25 years, the incidence
      of MS has been stable rather than increasing. Systematic longitudinal follow-up
      studies are essential to calculate reliable prevalence and incidence rates in MS.
      The results suggest that both methodologic and environmental factors are
      essential in determining the distribution of MS.

PMID- 16434651
TI  - Longitudinal cognitive changes in traumatic brain injury: a 30-year follow-up
      study.
AB  - OBJECTIVE: To evaluate longitudinal cognitive changes in patients over three
      decades following traumatic brain injury (TBI). METHOD: Two hundred ten patients
      with substantial TBI of variable severity were initially assessed between 1966
      and 1972 at Turku University Hospital (Finland). Of these, 61 patients could be
      studied using the same assessments in the follow-up examination, on average 30
      years after the TBI. The results of the follow-up assessment were also compared
      with an age- and education-matched control group. During each examination,
      patients were assessed with five subtests of the Wechsler Adult Intelligence
      Scale, three tests for episodic memory, and the general cognitive decline was
      determined. RESULTS: The general pattern of slight cognitive decline during a 30
      year follow-up contrasted with improvement in semantic memory. Women maintained
      their cognitive level, but men showed a decline during the follow-up, especially
      in visuospatial ability and visual memory. Younger patients were likely to
      maintain or even improve their cognitive functioning. CONCLUSIONS: Most of the
      patients had mild cognitive decline during the follow-up, but this decline was
      influenced by gender and age at injury. Unlike the long-term course in the other
      domains of cognition, semantic memory showed good recovery potential after
      traumatic brain injury (TBI). The profile of long-term cognitive decline after
      TBI seems to be qualitatively different from the early signs of dementia of the
      Alzheimer type.

PMID- 16434652
TI  - Chronic daily headache in adolescents: prevalence, impact, and medication
      overuse.
AB  - OBJECTIVES: To examine the prevalence, impact, and related medication use or
      overuse of primary chronic daily headache (CDH) among adolescents in a field
      sample. METHODS: The authors conducted a two-phase CDH survey of all students
      from ages 12 to 14 years in five selected middle schools in Taiwan. Subjects with
      CDH in the past year were identified and interviewed by neurologists. CDH was
      defined as headache occurring at a frequency of 15 days/month or more, average of
      2 hours/day or more, for more than 3 months, and its subtypes were classified on
      the basis of the International Classification of Headache Disorders, 2nd edition.
      RESULTS: Of the 7,900 participants, 122 (1.5%) fulfilled the criteria for primary
      CDH in the past year. Girls had a higher prevalence (2.4%) than boys (0.8%) (p <
      0.001). Of the CDH subjects, 88 (72%) could be classified into either chronic
      tension-type headache (65.6%) or chronic migraine (6.6%). None of them fulfilled
      the criteria of new daily-persistent headache or hemicrania continua. Twenty-four
      subjects (20%) overused medications. Eighty-two (67%) of all CDH subjects had
      migraine or probable migraine. In the past semester, most CDH subjects (65%) did
      not take any sick leave for headaches. Only 6 subjects consulted neurologists in
      the past year, and only 1 subject took headache prophylactic agents. CONCLUSIONS:
      Chronic daily headache (CDH) was common in a large nonreferred adolescent sample.
      Based on the International Classification of Headache Disorders, 2nd edition,
      criteria, chronic tension-type headache was the most common subtype; however, a
      majority of adolescents with CDH had headaches with features of migraine.

PMID- 16434653
TI  - Analgesic overuse among adolescents with headache: the Head-HUNT-Youth Study.
AB  - OBJECTIVES: To examine the association between the use of analgesics and primary
      headache disorders (i.e., migraine and tension-type headache) among adolescents
      in relation to age, gender, and headache frequency. METHODS: This cross
      sectional, population-based study was conducted in Norway from 1995 to 1997. The
      total study population consisted of 5,471 adolescents, 13 to 18 years of age, who
      were interviewed about their headache complaints and completed a comprehensive
      questionnaire including use of analgesics. RESULTS: The prevalence of daily
      headache associated with analgesic use was 0.5%, with a higher rate for girls
      (0.8%) than for boys (0.2%). There was a significant association for both genders
      between analgesic use and headache, although most pronounced for migraine. There
      was a significant linear relationship between analgesic use and headache
      frequency. Analgesic use was more common among girls than boys and increased with
      age both for those with and those without headache. CONCLUSIONS: The use of
      analgesics is common among adolescents with headache, especially among girls.
      Although this study did not directly evaluate for medication-overuse headache,
      the trend of frequent analgesic use suggests this possibility. Parents and
      physicians should increase their awareness of potential analgesic overuse,
      especially among adolescents with frequent headache.

PMID- 16434654
TI  - Embolization of pulmonary arteriovenous malformations and decrease in prevalence
      of migraine.
AB  - OBJECTIVE: To determine if embolization of pulmonary arteriovenous malformations
      (PAVMs) decreases the occurrence of migraine. METHODS: All 105 patients with
      hereditary hemorrhagic telangiectasia (HHT), minimum age 16 years, who underwent
      an embolization of PAVM in our hospital between June 1995 and April 2004, were
      included in this study. A structured headache questionnaire was sent to all
      patients and focused on two periods: 1 year before and at least 6 months after
      embolization. Two independent neurologists diagnosed migraine according to the
      International Headache Society criteria. RESULTS: Eighty-four patients (80%) sent
      back the questionnaire (mean age 47.8 +/- 15.1 years, 51 female). Median follow
      up time was 48 months (first quartile: 23 months; third quartile: 66 months). The
      overall prevalence of migraine decreased from 45.2% before to 34.5% after
      embolization (p = 0.01). The prevalence of migraine with aura decreased from
      33.3% before to 19.0% after embolization (p = 0.002). The severity of headache
      attacks decreased in patients who still had migraine (p = 0.15) or migraine with
      aura after embolization (p = 0.11). CONCLUSION: Embolization of pulmonary
      arteriovenous malformations in patients with hereditary hemorrhagic
      telangiectasia seems to be related to a decrease in prevalence of migraine,
      suggesting that the presence of a right-to-left shunt rather than the
      localization of this shunt plays a causative role in the pathogenesis of
      migraine.

PMID- 16434655
TI  - Antiplatelet use after intracerebral hemorrhage.
AB  - BACKGROUND: Survivors of intracerebral hemorrhage are at risk for recurrent
      intracerebral hemorrhage and ischemic cardiovascular and cerebrovascular disease.
      OBJECTIVE: To determine whether antiplatelet therapy increases the risk of
      recurrent intracerebral hemorrhage. METHODS: The authors reviewed data from
      consecutive survivors of primary intracerebral hemorrhage enrolled in a single
      center prospective cohort study. Survivors were followed by telephone interview;
      recurrent intracerebral hemorrhage and post-index antiplatelet agent use and
      duration were recorded. Cox proportional hazards models was used with
      antiplatelet agent exposure as a time-dependent variable to assess the effect of
      antiplatelet agent use on recurrent intracerebral hemorrhage, stratified by lobar
      and deep hemispheric location. RESULTS: Recurrent intracerebral hemorrhage was
      more common in survivors of lobar hemorrhage compared with survivors of deep
      hemorrhage (cumulative 2-year rate 22% vs 4%; p = 0.007). Antiplatelet agents
      were prescribed in 22% of intracerebral hemorrhage survivors (27/127 lobar, 19/80
      deep hemispheric), most commonly for prevention of ischemic heart disease.
      Antiplatelet agent use was not associated with intracerebral hemorrhage
      recurrence in survivors of either lobar hemorrhage (hazard ratio [HR] 0.8, 95% CI
      0.3 to 2.3, p = 0.73) or of deep hemorrhage (HR 1.2, 95% CI 0.1 to 14.3, p =
      0.88). CONCLUSION: Antiplatelet agent use is relatively common following
      intracerebral hemorrhage but did not appear to be associated with a large
      increased risk of intracerebral hemorrhage recurrence in this observational
      study.

PMID- 16434656
TI  - Efficacy and safety of vardenafil in men with erectile dysfunction caused by
      spinal cord injury.
AB  - OBJECTIVE: To assess the efficacy and tolerability of vardenafil in men with
      erectile dysfunction (ED) due to traumatic spinal cord injury (SCI). METHODS: In
      this multicenter, double-blind, placebo-controlled, parallel-group 12-week study,
      418 men aged 18 years and older with ED for more than 6 months consequent to SCI
      were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks,
      then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments
      included the erectile function (EF) domain score of the International Index of
      Erectile Function questionnaire and diary questions regarding penetration,
      maintenance of erection to completion of intercourse, and ejaculation. RESULTS:
      Baseline patient characteristics were similar in the vardenafil (mean age 40
      years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores
      were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF
      domain score in the vardenafil group improved to 22.0 (mild ED) at last
      observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12
      weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59%
      vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs
      placebo (all p < 0.001). The most frequently reported drug-related adverse events
      were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%),
      nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%,
      placebo 0%). CONCLUSION: Vardenafil significantly improved erectile and
      ejaculatory function and was generally well tolerated in men with erectile
      dysfunction due to spinal cord injury.

PMID- 16434657
TI  - White matter damage on diffusion tensor imaging correlates with age-related
      cognitive decline.
AB  - BACKGROUND: Damage to white matter tracts, resulting in "cerebral disconnection,"
      may underlie age-related cognitive decline. METHODS: Using diffusion tensor MRI
      (DTI) to investigate white matter damage, and magnetic resonance spectroscopy
      (MRS) to look at its underlying pathologic basis, the authors investigated the
      relationship between white matter structure and cognition in 106 healthy middle
      aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD)
      values, whole brain white matter histograms, and regions of interest placed in
      the white matter of the centrum semiovale were analyzed. Correlations with
      executive function, working memory, and information-processing speed were
      performed. RESULTS: There was a progressive reduction in FA and increase in
      diffusivity with age in both region of interest (r = 0.551, p < 0.001), and whole
      brain histograms (r = 0.625, p < 0.001). DTI values correlated with performance
      in all three cognitive domains. After controlling for age, DTI parameters
      correlated with working memory but not with the other two cognitive domains. MRS
      studies found a correlation of N-acetyl aspartate, a neuronal marker, with DTI
      parameters (r = 0.253, p < 0.05). CONCLUSION: The results are consistent with
      white matter damage due to axonal loss, causing age- related cognitive decline.
      Working memory may be particularly dependent on complex networks dependent on
      white matter connections.

PMID- 16434659
TI  - Natural history of Type A Niemann-Pick disease: possible endpoints for
      therapeutic trials.
AB  - OBJECTIVE: To describe the disease course and natural history of Type A Niemann
      Pick disease (NPD). METHODS: Ten patients with NPD-A (six male, four female; age
      range at entry: 3 to 6 months) were serially evaluated including clinical
      neurologic, ophthalmologic, and physical examinations, and assessment of
      development. Laboratory analyses, abdominal and brain ultrasounds, and chest
      radiographs also were obtained and information on intercurrent illnesses and
      cause of mortality was collected. RESULTS: All affected infants had a normal
      neonatal course and early development. The first symptom detected in all patients
      was hepatosplenomegaly. Developmental age did not progress beyond 10 months for
      adaptive behavior, 12 months for expressive language, 9 months for gross motor
      skills, and 10 months for fine motor skills. Non-neurologic symptoms included
      frequent vomiting, failure to thrive, respiratory infections, irritability, and
      sleep disturbance. Neurologic examination at the time of presentation was normal
      in most patients. Later neurologic examinations revealed progressive hypotonia
      with loss of the deep tendon reflexes. All patients had cherry red spots by 12
      months. The median time from diagnosis to death was 21 months. The cause of death
      was respiratory failure in nine patients and complications from bleeding in the
      tenth. CONCLUSIONS: The clinical course in Type A Niemann-Pick disease is similar
      among affected patients and is characterized by a relentless neurodegenerative
      course that leads to death, usually within 3 years.

PMID- 16434658
TI  - Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of
      Nigerian Yoruba.
AB  - OBJECTIVE: To examine the relationship between cholesterol and other lipids, APOE
      genotype, and risk of Alzheimer disease (AD) in a population-based study of
      elderly Yoruba living in Ibadan, Nigeria. METHODS: Blood samples and clinical
      data were collected from Yoruba study participants aged 70 years and older (N =
      1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal
      epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high
      density lipoprotein (HDL), and triglyceride levels were measured in fasting blood
      samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by
      consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's
      Disease and Related Disorders Association criteria. RESULTS: Logistic regression
      models showed interaction after adjusting for age and gender between APOE
      epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p =
      0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036).
      Increasing levels of cholesterol and LDL were associated with increased risk of
      AD in individuals without the APOE-epsilon4 allele, but not in those with APOE
      epsilon4. There was no significant association between levels of triglycerides
      and AD risk in those without APOE-epsilon4. CONCLUSIONS: There was a significant
      interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease
      (AD) in the Yoruba, a population that has lower cholesterol levels and lower
      incidence rates of AD compared to African Americans. APOE status needs to be
      considered when assessing the relationship between lipid levels and AD risk in
      population studies.

PMID- 16434660
TI  - Brain volume loss in MCI predicts dementia.
AB  - Rates of temporal horn volume change were significantly greater in the subjects
      with mild cognitive impairment who were developing dementia vs those who remained
      stable.

PMID- 16434661
TI  - Hippocampal atrophy in Alzheimer disease: age matters.
AB  - Hippocampal atrophy is a marker of Alzheimer disease (AD). It remains unclear
      whether this holds true for younger patients as well. Hippocampal volume was
      measured on MRI scans of 103 clinically diagnosed AD patients and 73 controls
      (aged 51 to 85 years). Aging and AD were independently associated with smaller
      hippocampal volume. Both young and old AD patients have hippocampal atrophy
      abnormal for age. Age-dependent criteria for hippocampal atrophy, suggestive of
      AD, are needed.

PMID- 16434662
TI  - Surviving glioblastoma for more than 5 years: the patient's perspective.
AB  - The authors performed a comprehensive analysis of the functional outcome of 10
      patients who had survived 5 years from a diagnosis of glioblastoma. Neurologic
      deficits were mild in most patients, but neuropsychological testing demonstrated
      cognitive deficits in all patients. Depression and anxiety were common. Although
      most patients thought that their social functioning and work ability were
      impaired, little reduction in overall quality of life was perceived.

PMID- 16434663
TI  - Interleukin-8 CSF levels predict survival in patients with leptomeningeal
      metastases.
AB  - Median survival of patients with leptomeningeal metastases (LM) is 4 to 6 months,
      with a few long-term survivors. Current prognostic factors for survival have
      limited value. The authors measured the CSF levels of nine inflammatory proteins
      in 57 patients with LM and determined their prognostic value. High interleukin
      (IL)-8 CSF levels predicted short-term survival independently. The data indicate
      that IL-8 CSF levels may serve as a prognosticator in patients with LM, but
      prospective validation is needed.

PMID- 16434664
TI  - Oligodendroglial tumor chemotherapy using "decreased-dose-intensity" PCV: a
      Singapore experience.
AB  - The authors propose "decreased-dose-intensity" PCV (procarbazine, lomustine
      [CCNU], and vincristine) chemotherapy for Asian patients with oligodendroglial
      tumors. In this study, all seven patients with oligodendroglioma (OD) and eight
      with anaplastic oligodendroglioma (AO) had objective responses or stable disease.
      Median progression-free survival was greater than 29 months (OD) and 36.5 months
      or greater (AO); 86% of patients with OD and 63% with AO remain progression-free.
      Twenty-four Common Toxicity Criteria Grade 3/4 adverse events were noted.

PMID- 16434665
TI  - Paroxysmal vertigo as the presenting symptom of Fabry disease.

PMID- 16434667
TI  - Coenzyme Q10 deficiency and isolated myopathy.
AB  - Three unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency
      presented at 32, 29, and 6 years of age with proximal muscle weakness and
      elevated serum creatine kinase (CK) and lactate levels, but without
      myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy,
      combined deficiency of respiratory chain complexes I and III, and CoQ10 levels
      below 50% of normal. Oral high-dose CoQ10 supplementation improved muscle
      strength dramatically and normalized serum CK.

PMID- 16434668
TI  - The utility of skin biopsy for prediction of progression in suspected small fiber
      neuropathy.
AB  - Twenty-eight patients with sensory complaints of unknown etiology had repeated
      skin biopsies. Patients with large nerve fiber swellings on initial biopsy showed
      a decline in epidermal nerve fiber density on repeated biopsies (p < 0.05 within
      group; p < 0.05 vs those without swellings). Patients without nerve fiber
      swellings did not have changes in nerve fiber density between biopsies. Patients
      with large nerve fiber swellings were most likely to present clinically with
      paresthesias (p < 0.05).

PMID- 16434666
TI  - Creatine in Huntington disease is safe, tolerable, bioavailable in brain and
      reduces serum 8OH2'dG.
AB  - In a randomized, double-blind, placebo-controlled study in 64 subjects with
      Huntington disease (HD), 8 g/day of creatine administered for 16 weeks was well
      tolerated and safe. Serum and brain creatine concentrations increased in the
      creatine-treated group and returned to baseline after washout. Serum 8-hydroxy-2'
      deoxyguanosine (8OH2'dG) levels, an indicator of oxidative injury to DNA, were
      markedly elevated in HD and reduced by creatine treatment.

PMID- 16434669
TI  - Factors influencing nerve regeneration in a trial of timcodar dimesylate.
AB  - The authors assessed the ability of the neurophilin compound, timcodar
      dimesylate, to accelerate the return of epidermal nerve fiber density (ENFD)
      after a standardized nerve injury in a randomized double blind, placebo
      controlled trial. While there was no difference in the regeneration rate between
      the treatment and placebo arms, the baseline ENFD (p = 0.006), height (p = 0.02),
      and race (p = 0.03) were associated with the regeneration rate.

PMID- 16434670
TI  - Seizures and their outcome in progressive multifocal leukoencephalopathy.
AB  - Seizures are not expected in progressive multifocal leukoencephalopathy (PML), a
      condition considered to be restricted to the white matter. Review of medical
      records of 89 patients with possible or proven PML showed an 18% prevalence of
      seizures. Seizures usually responded well to treatment and did not affect
      survival. The presence of PML lesions immediately adjacent to the hemispheric
      cortex was the only risk factor associated with seizures in this population.

PMID- 16434671
TI  - Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS.
AB  - The authors calculated the progression rate (DeltaFS) using the total revised ALS
      Functional Rating Scale (ALSFRS-R) and symptom duration at diagnosis in 82
      Japanese patients with ALS. Survival (death or tracheostomy) differed
      significantly with the DeltaFS and postdiagnostic period according to log-rank
      testing, but Cox proportional hazards modeling revealed no strong association
      between total ALSFRS-R and mortality, suggesting that the DeltaFS provides an
      additional predictive index beyond ALSFRS-R alone.

PMID- 16434672
TI  - Bipolar deep brain stimulation permits routine EKG, EEG, and polysomnography.
AB  - As the population of patients treated with deep brain stimulation (DBS) grows and
      the patients age, more will require routine or emergent electrophysiologic tests.
      DBS artifact may render these uninterpretable, whereas stopping DBS may release
      symptoms that confound evaluation. The authors find that monopolar, but not
      bipolar, stimulation produces significant artifact during EKG, EEG, and
      polysomnography.

PMID- 16434673
TI  - An MRI view of a ruptured dermoid cyst.

PMID- 16434674
TI  - Peri-ictal lateralizing signs in children: blinded multiobserver study of 100
      children < or =12 years.
AB  - Seizures in 100 children with partial epilepsy, 61% of temporal lobe origin, were
      assessed by multiple observers for lateralizing signs (LSs). Most LSs achieved
      very good interobserver agreement and high predictive value. Seventy-five percent
      of children produced LSs. Lack of LSs occurred more frequently among younger
      children, while some LSs appeared more frequently at older ages. Many frequent
      and reliable LSs were independent of age. LSs may help in the presurgical
      evaluation of infants and young children.

PMID- 16434675
TI  - The effect of glatiramer acetate treatment on pre-existing headaches in patients
      with MS.
AB  - During the first 6 months of glatiramer acetate therapy in 82 consecutive
      patients with multiple sclerosis, in only 6% frequency of pre-existing headaches
      increased by more than 50%. This is less than the headache aggravation reported
      in an earlier study in up to 35% of patients during the first 6 months on
      interferon beta.

PMID- 16434676
TI  - Substrate reduction therapy in the infantile form of Tay-Sachs disease.
AB  - Substrate reduction therapy (SRT) with miglustat has been proposed for treatment
      of some lysosomal storage disorders. Based on the positive experience in Gaucher
      disease and experimental data in Tay-Sachs (TSD) and Sandhoff animal models, the
      authors investigated the clinical efficacy of SRT in two patients with infantile
      TSD. SRT could not arrest the patients' neurologic deterioration. However, a
      significant drug concentration in CSF as well as macrocephaly prevention were
      observed.

PMID- 16434677
TI  - Detection of floccular hypometabolism in downbeat nystagmus by fMRI.
AB  - The authors evaluated floccular activity with fMRI during the performance of
      vertical smooth pursuit eye movements in four patients with downbeat nystagmus
      (DBN) due to cerebellar degeneration and in 16 healthy controls. Region of
      interest analysis revealed a significantly diminished activation of both
      floccular lobes during downward but not upward pursuit in DBN. These imaging data
      support the view that a functional deficiency of the flocculi in downward pursuit
      causes DBN.

PMID- 16434678
TI  - Trends in acoustic neuroma and cellular phones: is there a link?

PMID- 16434679
TI  - Gentamicin treatment in McArdle disease: failure to correct myophosphorylase
      deficiency.

PMID- 16434680
TI  - First symptom in sporadic Creutzfeldt-Jakob disease.

PMID- 16434681
TI  - Acute motor conduction block neuropathy followed by axonal degeneration and poor
      recovery.

PMID- 16434683
TI  - Natural selection.

PMID- 16434682
TI  - Relapsing cervical cord lesions on MRI in patients with HTLV-I-associated
      myelopathy.

PMID- 16434684
TI  - Visual field defect and intracerebral hemorrhage associated with use of
      vardenafil (Levitra).

PMID- 16434685
TI  - Sudden deafness from stroke.

PMID- 16434686
TI  - Excess of serum copper not related to ceruloplasmin in Alzheimer disease.

PMID- 16434687
TI  - Reading impairment in the neuronal migration disorder of periventricular nodular
      heterotopia.

PMID- 16434688
TI  - SPATTER! SPATTER! SPATTER! Workers' health and the spray machine debate.
AB  - A conflict between industrialization and worker health developed in the painting
      industry during the early 1900s with the introduction of the spray machine. This
      technological innovation allowed the application of paint at greater speed and
      lower cost than hand painting and increased the rate at which painters were
      exposed to lead and other toxins contained in paint. From roughly 1919 to 1931,
      the painters' trade union clashed with employers, paint manufacturers, and
      legislatures over the impact of the spray machine on the health of workers and
      the need to enact legislation to regulate its use. While painters made gains on
      local, state, and national levels during the 1920s to prevent the use of the
      spray machine, their efforts ultimately failed.

PMID- 16434689
TI  - "The doctors' choice is America's choice": the physician in US cigarette
      advertisements, 1930-1953.
AB  - In the 1930s and 1940s, smoking became the norm for both men and women in the
      United States, and a majority of physicians smoked. At the same time, there was
      rising public anxiety about the health risks of cigarette smoking. One strategic
      response of tobacco companies was to devise advertising referring directly to
      physicians. As ad campaigns featuring physicians developed through the early
      1950s, tobacco executives used the doctor image to assure the consumer that their
      respective brands were safe. These advertisements also suggested that the
      individual physicians' clinical judgment should continue to be the arbiter of the
      harms of cigarette smoking even as systematic health evidence accumulated.
      However, by 1954, industry strategists deemed physician images in advertisements
      no longer credible in the face of growing public concern about the health
      evidence implicating cigarettes.

PMID- 16434690
TI  - The macrophage scavenger receptor CD163: endocytic properties of cytoplasmic tail
      variants.
AB  - CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp
      Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant
      and two long tail variants. Reverse transcriptase-polymerase chain reaction
      analysis indicated that all three CD163 variants are substantially expressed in
      blood, liver, and spleen, and the short tail variant is the predominant mRNA
      species. Using cell transfectants in which cDNA encoding the CD163 variants was
      inserted at the same site in the genome, we evaluated the expression and
      endocytic properties of the tail variants. Ligand uptake analysis showed that
      cells expressing the CD163 short tail variant exhibited a higher capacity for
      ligand endocytosis than cells expressing the CD163 long tail variants. The
      difference in endocytic activity was explained by confocal microscopic analysis,
      showing marked deviations in subcellular distribution. Surface expression was far
      most pronounced for the CD163 short tail variant, whereas the long tail variants
      were most abundant in the Golgi region/endosomes. Mutational change of a putative
      signal for endocytosis (Tyr-Arg-Glu-Met), present in a common part of the
      cytoplasmic tail of the variants, almost completely inactivated the endocytic
      activity of the short tail variant. In conclusion, the three physiological tail
      variants of CD163 may contribute to Hp-Hb endocytosis by means of the common
      ligand-binding region and endocytic signal. However, the high mRNA expression
      level and relatively high endocytic capacity of the short tail variant suggest
      that it accounts for the majority of Hp-Hb uptake from the circulation, whereas
      the long tail variants may have yet-unknown intracellular roles.

PMID- 16434691
TI  - Detection and properties of the human proliferative monocyte subpopulation.
AB  - Peripheral blood monocyte subpopulations have been reported and can give rise to
      diverse, differentiated phenotypes. A subpopulation(s) of human monocytes can
      proliferate in vitro in response to macrophage-colony stimulating factor (M-CSF;
      or CSF-1). This population, termed the proliferative monocyte (PM), is presumably
      less mature than other monocytes; however, it has not been defined further.
      Previous studies monitoring the frequency of the slowly cycling PM from different
      donors indicated that the assay for their reproducible measurement required
      improvement. We demonstrate that for optimal PM detection, high 5-bromo-2'
      deoxyuridine concentrations are required over a delayed and wide time-frame.
      Surface marker phenotyping by flow cytometry showed that freshly isolated PM are
      CD14+ and could be distinguished from two other human monocyte subpopulations,
      namely, the CD14lo CD16+ and CD14lo CD64- subsets. PM express relatively high
      levels of CD64 and CD33 but have relatively low CD13 expression; they are also c
      Fms+ and human leukocyte antigen-DR+. Labeling with carboxyfluorescein diacetate
      succinimidyl ester (CFSE) enabled the estimation of the number of PM divisions
      over time. Following CFSE labeling and culture, PM were sorted from the
      nonproliferating population and shown to have a distinctive, spindle-shaped
      morphology and higher capacity to form multinucleated, tartrate-resistant acid
      phosphatase+ cells in the presence of M-CSF and receptor activator of nuclear
      factor-kappaB ligand. The phenotype and properties of the PM subpopulation were
      examined as a prelude to determining its role in disease using methods that can
      be applied to clarify human monocyte heterogeneity.

PMID- 16434692
TI  - Different effects of adiponectin isoforms in human monocytic cells.
AB  - Adiponectin (APM) is an adipocyte-derived adipokine with immunosuppressive,
      antidiabetic, and antiatherosclerotic properties. Low molecular weight (LMW)- and
      higher molecular weight (HMW)-APM circulate in the serum and activate different
      signaling pathways. We were interested to see whether LMW-APM exerts different
      effects on monocytic cells compared with the HMW isoform. Therefore, the effects
      of recombinant LMW-APM produced in insect cells and the APM from higher
      eukaryotic cells containing HMW forms on monocytic cells were investigated with
      respect to apoptosis and inflammation. LMW- and HMW-APM induce apoptosis in
      nondifferentiated THP-1 cells, reduce macrophage scavenger receptor (MSR) A mRNA
      expression, and stimulate phosphorylation of adenosine monophosphate-activated
      protein kinase (AMPK). However, HMW-APM induces the secretion of interleukin (IL)
      6 in human monocytes and THP-1 cells but does not suppress lipopolysaccharide
      (LPS)-induced IL-6 secretion. In contrast, LMW-APM reduces LPS-mediated IL-6
      release and furthermore, stimulates IL-10 secretion, most likely by reducing the
      abundance of inhibitor of nuclear factor (NF)-kappaB kinase beta, leading to a
      diminished nuclear translocation of NF-kappaB p65. Our data indicate that the
      different APM isoforms do share common effects on monocytic cells but also induce
      isoform-specific responses. Although apoptosis, the activation of AMPK, and the
      reduction of MSR are mediated by all APM isoforms, only LMW-APM displays anti
      inflammatory properties.

PMID- 16434694
TI  - A (G->C) transversion in the 3' UTR of the human ECP (eosinophil cationic
      protein) gene correlates to the cellular content of ECP.
AB  - Eosinophil cationic protein (ECP) is a cytotoxic protein produced by and secreted
      from human eosinophil granulocytes. ECP may be involved in the injury of
      epithelial cells in allergic diseases such as asthma. The objectives were to
      determine the prevalence of the ECP gene polymorphism 562(G > C) in apparently
      healthy subjects and subjects with allergy and relate the prevalence to clinical
      disease and to serum and cellular levels of ECP. The 562(G > C) ECP gene
      polymorphism was determined by gene sequencing of the ECP gene from DNA prepared
      from 163 apparently healthy subjects and 151 subjects with allergic and
      nonallergic asthma or other diseases. ECP was measured by a sensitive
      radioimmunoassay. A polymorphism was detected at position 562, which mapped to
      the 3' untranslated region (UTR) of the gene encoding the ECP (RNase 3). Sixty
      nine percent of the population had the 562GG genotype and 4%, the 562CC genotype.
      The cellular content of ECP in peripheral blood eosinophil granulocytes was
      significantly lower in cells from subjects with the 562GC (4.6+/-1.5 microg/10(6)
      eosinophils) and 562CC (3.2+/-0.7 microg/10(6) eosinophils) genotypes as compared
      with those with the 562GG genotype (6.0+/-1.9 microg/10(6) eosinophils; P <
      0.001). A close link was found to the 434(G > C) ECP gene polymorphism.
      Associations between the 562(G > C) polymorphism or haplotypes of the two
      polymorphisms to allergy were not found. The 562(G > C) polymorphism in the 3'
      end of the UTR of the ECP gene may determine the ECP content in human
      eosinophils, but unlike the 434(G > C) polymorphism, the 562(G > C) polymorphism
      is not related to allergy.

PMID- 16434693
TI  - The lectin jacalin plus costimulation with anti-CD28 antibody induces
      phosphorylation of p38 MAPK and IL-4 synthesis-I.
AB  - Costimulatory signals play an important role in the development of T helper cell
      type 1 (Th1) or Th2 type. Little is known about jacalin plus CD28-mediated
      signaling and cytokine secretion. In the present study, we analyzed the
      intracellular signaling events following stimulation of CD4+ T cells with jacalin
      plus CD28 cross-linking (CD28XL) with anti-CD28 antibody. Our results indicate
      enhanced phosphorylation of Tec and linker for activation of T cells when
      compared with stimulation with jacalin alone or CD28XL alone. Stimulation with
      jacalin or CD28XL appears to be insufficient to induce interleukin (IL)-4
      secretion; however, CD28XL followed by stimulation with jacalin resulted in
      enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and
      increased secretion of IL-4. However, compared with stimulation with phorbol 12
      myristate 13-acetate plus ionomycin, jacalin plus CD28XL resulted in decreased
      levels of tumor necrosis factor alpha secretion. Addition of p38 inhibitor,
      SB203580, inhibited p38 phosphorylation and IL-4 secretion. These data suggest
      that jacalin stimulation alone appears to be insufficient for Th2 development,
      and addition of CD28 costimulation induced Th2 generation. We propose that
      jacalin plus CD28XL induces Th2 differentiation via activation of p38 MAPK.

PMID- 16434695
TI  - CCL5-enhanced human immature dendritic cell migration through the basement
      membrane in vitro depends on matrix metalloproteinase-9.
AB  - The proinflammatory chemokine CC chemokine ligand 5 (CCL5) is a potent
      chemoattractant of immature dendritic cells (iDCs). It remains to be elucidated
      whether CCL5 may also enhance iDC migration through the basement membrane by
      affecting matrix metalloproteinase (MMP)-9 secretion. In this study, iDCs were
      differentiated in vitro from human monocytes of healthy donors. Zymographic
      analysis of cellular membranes of nontreated iDCs revealed a basal secretion of
      the pro- and active MMP-9, whereas only pro-MMP-9 was detected in conditioned
      media. Increasing concentrations of CCL5 significantly enhanced MMP-9 secretion
      by iDCs, peaking at 100 ng/ml, which optimally increased iDC migration through a
      reconstituted basement membrane (Matrigel) in vitro. The CCL5-enhanced secretion
      of MMP-9 occurred early (2 h) and was maintained at least for 10 h. A significant
      increase in MMP-9 mRNA synthesis was detected by reverse transcriptase-polymerase
      chain reaction, only at 6 h of CCL5 treatment, which suggests that the early
      effect of CCL5 (0-4 h) on MMP-9 secretion was independent of mRNA synthesis,
      whereas the more delayed effect (6-10 h) could be mediated through an increase in
      MMP-9 gene expression. In a Matrigel migration assay, the CCL5-enhanced iDC
      migration was reduced significantly by specific inhibitors of MMP-9, such as
      tissue inhibitor of metalloproteinase-1 or an anti-MMP-9 antibody, which
      indicates that iDC migration through the basement membrane depends on MMP-9.
      These results suggest that under inflammatory conditions, the chemokine CCL5 may
      enhance iDC migration through the basement membrane by rapidly increasing their
      MMP-9 secretion.

PMID- 16434696
TI  - CCL2 as a trigger of manifestations of compensatory anti-inflammatory response
      syndrome in mice with severe systemic inflammatory response syndrome.
AB  - Patients with compensatory anti-inflammatory response syndrome (CARS) are at a
      higher risk for infection with various opportunistic pathogens. CARS develops
      commonly in association with the manifestation of systemic inflammatory response
      syndrome (SIRS). In the present study, the role of SIRS-associated soluble
      factors on the CARS development was examined in mice with pancreatitis, a carrier
      of typical SIRS. Following the production of SIRS-related cytokines [tumor
      necrosis factor alpha and interleukin (IL)-1beta], CC chemokine ligand 2 (CCL2),
      IL-4, and IL-10 (typical CARS cytokines) were detected in the sera of mice with
      pancreatitis. CCL2 has been described as an essential chemokine for the T helper
      cell type 2 manifestation. CARS effector cells (cells with an ability to produce
      IL-4 and IL-10) were not generated from normal T cells after stimulation with
      SIRS-related cytokines. However, these cells were generated from normal T cells
      after cultivation with peripheral blood neutrophils (PMN) from SIRS mice in a
      dual-chamber transwell. Normal T cells did not convert to CARS effector cells
      after transwell cultures with PMN from normal mice. CCL2 was detected in culture
      fluids of PMN from SIRS mice, and PMN from normal mice did not produce CCL2 into
      their culture fluids. CARS effector cells did not appear in PMN-depleted SIRS
      mice or SIRS mice treated with anti-CCL2 monoclonal antibody, and these cells
      were demonstrated in PMN-depleted SIRS mice after treatment with recombinant
      murine CCL2. These results indicate that CCL2 produced by PMN from SIRS mice is
      an active molecule on the SIRS-associated CARS manifestation.

PMID- 16434697
TI  - Hypoxia reduces the output of matrix metalloproteinase-9 (MMP-9) in monocytes by
      inhibiting its secretion and elevating membranal association.
AB  - Cellular hypoxia, characterizing tumors, ischemia, and inflammation induce
      recruitment of monocytes/macrophages, immobilize them at the hypoxic site, and
      alter their function. To migrate across the extracellular matrix and as part of
      their inflammatory functions, monocytes and macrophages secrete proteases,
      including matrix metalloproteinase-9 (MMP-9), whose expression is induced by
      proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-alpha)]. We
      show that hypoxia (<0.3% O2 for 48 h) reduced the output of TNF-alpha-induced
      proMMP-9 by threefold (P < 0.01) in the U937 monocytic cell line and in primary
      human monocytes. TNF-alpha induced MMP-9 transcription by threefold, but no
      significant difference was observed in MMP-9 mRNA steady-state between normoxia
      and hypoxia, which inhibited the trafficking of proMMP-9 via secretory vesicles
      and increased the intracellular accumulation of proMMP-9 in the cells by 47% and
      62% compared with normoxia (P < 0.05), as evaluated by zymography of cellular
      extracts and confocal microscopy, respectively. Secretion of proMMP-9 was reduced
      by the addition of cytochalazin B or nocodazole, which inhibits the
      polymerization of actin and tubulin fibers, or by the addition of the Rho kinase
      inhibitor Y27632, suggesting the involvement of the cytoskeleton and the Rho
      GTPases in the process of enzyme secretion. Furthermore, attachment of proMMP-9
      to the cell membrane increased after hypoxia via its interactions with surface
      molecules such as CD44. In addition, the reduced migration of monocytes in
      hypoxia was shown to be mediated, at least partially, by secreted MMP-9. Thus,
      hypoxia post-translationally reduced the secreted amounts of proMMP-9 by using
      two mutually nonexclusive mechanisms: mostly, inhibition of cellular trafficking
      and to a lesser extent, attachment to the membrane.

PMID- 16434698
TI  - A simple and effective chromosome modification method for large-scale deletion of
      genome sequences and identification of essential genes in fission yeast.
AB  - The technologies for chromosome modification developed to date are not
      satisfactorily universal, owing to the typical requirements for special enzymes
      and sequences. In the present report, we propose a new approach for chromosome
      modification in Schizosaccharomyces pombe that does not involve any special
      enzymes or sequences. This method, designated the 'Latour system', has wide
      applicability with extremely high efficiency, although both the basic principle
      and the operation are very simple. We demonstrate the ability of the Latour
      system to discriminate essential genes, with a long chromosomal area of 100 kb
      containing 33 genes deleted simultaneously and efficiently. Since no foreign
      sequences are retained after deletion using the Latour system, this system can be
      repeatedly applied at other sites. Provided that a negative selectable marker is
      available, the Latour system relies solely upon homologous recombination, which
      is highly conserved in living organisms. For this reason, it is expected that the
      system will be applicable to various yeasts.

PMID- 16434699
TI  - MicroRNA expression profiling of single whole embryonic stem cells.
AB  - MicroRNAs (miRNAs) are a class of 17-25 nt non-coding RNAs that have been shown
      to have critical functions in a wide variety of biological processes during
      development. Recently developed miRNA microarray techniques have helped to
      accelerate research on miRNAs. However, in some instances there is only a limited
      amount of material available for analysis, which requires more sensitive
      techniques that can preferably work on single cells. Here we demonstrate that it
      is possible to analyse miRNA in single cells by using a real-time PCR-based 220
      plex miRNA expression profiling method. Development of this technique will
      greatly facilitate miRNA-related research on cells, such as the founder
      population of primordial germ cells where rapid and dynamic changes occur in a
      few cells, and for analysing heterogeneous population of cells. In these and
      similar cases, our method of single cell analysis is critical for elucidating the
      diverse roles of miRNAs.

PMID- 16434700
TI  - Complex interactions of HIV-1 nucleocapsid protein with oligonucleotides.
AB  - The HIV-1 nucleocapsid (NC) protein is a small, basic protein containing two
      retroviral zinc fingers. It is a highly active nucleic acid chaperone; because of
      this activity, it plays a crucial role in virus replication as a cofactor during
      reverse transcription, and is probably important in other steps of the
      replication cycle as well. We previously reported that NC binds with high
      affinity to the repeating sequence d(TG)n. We have now analyzed the interaction
      between NC and d(TG)4 in considerable detail, using surface plasmon resonance
      (SPR), tryptophan fluorescence quenching (TFQ), fluorescence anisotropy (FA),
      isothermal titration calorimetry (ITC) and electrospray ionization Fourier
      transform mass spectrometry (ESI-FTMS). Our results show that the interactions
      between these two molecules are surprisngly complex: while the K(d) for binding
      of a single d(TG)4 molecule to NC is only approximately 5 nM in 150 mM NaCl, a
      single NC molecule is capable of interacting with more than one d(TG)4 molecule,
      and conversely, more than one NC molecule can bind to a single d(TG)4 molecule.
      The strengths of these additional binding reactions are quantitated. The
      implications of this multivalency for the functions of NC in virus replication
      are discussed.

PMID- 16434701
TI  - Regulation of the human p21(waf1/cip1) gene promoter via multiple binding sites
      for p53 and the vitamin D3 receptor.
AB  - The main regulator of the human tumor suppresser gene p21(waf1/cip1) is the
      transcription factor p53, but more recently it has been suggested to be a primary
      anti-proliferative target for the nuclear receptor VDR in the presence of its
      ligand 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). To identify VDR
      responding regions, we analyzed 20 overlapping regions covering the first 7.1 kb
      of the p21(waf1/cip1) promoter in MCF-7 human breast cancer cells using chromatin
      immuno-precipitation assays (ChIP) with antibodies against p53 and VDR. We
      confirmed two known p53 binding regions at approximate positions -1400 and -2300
      and identified a novel site at position -4500. In addition, we found three VDR
      associated promoter regions at positions -2300, -4500 and -6900, i.e. two regions
      showed binding for both p53 and VDR. In silico screening and in vitro binding
      assays using recombinant and in vitro translated proteins identified five p53
      binding sites within the three p53-positive promoter regions and also five
      1alpha,25(OH)2D3 response elements within the three VDR-positive regions.
      Reporter gene assays confirmed the expected responsiveness of the respective
      promoter regions to the p53 inducer 5-fluorouracil and 1alpha,25(OH)2D3.
      Moreover, re-ChIP assays confirmed the functionality of the three
      1alpha,25(OH)2D3-reponsive promoter regions by monitoring simultaneous occupancy
      of VDR with the co-activator proteins CBP, SRC-1 and TRAP220. Taken together, we
      demonstrated that the human p21((waf1/cip1)) gene is a primary 1alpha,25(OH)2D3
      responding gene with at least three VDR binding promoter regions, in two of which
      also p53 co-localizes.

PMID- 16434702
TI  - Rampant polyuridylylation of plastid gene transcripts in the dinoflagellate
      Lingulodinium.
AB  - Dinoflagellate plastid genes are believed to be encoded on small generally
      unigenic plasmid-like minicircles. The minicircle gene complement has reached
      saturation with an incomplete set of plastid genes (18) compared with typical
      functional plastids (60-200). While some of the missing plastid genes have
      recently been found in the nucleus, it is still unknown if additional genes, not
      located on minicircles, might also contribute to the plastid genome. Sequencing
      of tailed RNA showed that transcripts derived from the known minicircle genes
      psbA and atpB contained a homogenous 3' polyuridine tract of 25-40 residues. This
      unusual modification suggested that random sequencing of a poly(dA) primed cDNA
      library could be used to characterize the plastid transcriptome. We have
      recovered only 12 different polyuridylylated transcripts from our library, all of
      which are encoded on minicircles in several dinoflagellate species. The
      correspondence of all polyuridylylated transcripts with previously described
      minicircle genes thus supports the dinoflagellate plastid as harbouring the
      smallest genome of any functional chloroplast. Interestingly, northern blots
      indicate that the majority of transcripts are modified, suggesting that
      polyuridylylation is unlikely to act as a degradation signal as do the
      heterogeneous poly(A)-rich extensions of transcripts in cyanobacteria and other
      plastids.

PMID- 16434703
TI  - High ampicillin resistance in different biotypes and serotypes of Haemophilus
      influenzae colonizing the nasopharynx of healthy school-going Indian children.
AB  - Haemophilus influenzae is one of the main causes of otitis media, sinusitis,
      meningitis, pneumonia and septicaemia in children, and the development of
      ampicillin resistance in H. influenzae is a cause of serious concern. The aim of
      the present study was to determine the prevalence of ampicillin resistance in H.
      influenzae colonizing the nasopharynx of school-going healthy North Indian
      children, and to compare the distribution of different biotypes and serotype b in
      this population. A total of 2400 school-going healthy children from 45 rural and
      45 urban schools were enrolled. Nasopharyngeal swabs were collected from the
      children and cultured. H. influenzae was isolated from 1001 (41.7 %) of the 2400
      nasopharyngeal swabs collected. All these H. influenzae isolates were biotyped
      and serotyped, and their antibiotic susceptibility tested. All eight biotypes
      were present in this population. The most prevalent biotypes were I (19.6 %), II
      (16.8 %) and III (25.0 %). Of the 1001 isolates, 316 (31.6 %) were H. influenzae
      type b and 685 (68.4 %) were non-type b H. influenzae, and 22.9 % were resistant
      to ampicillin, 41.9 % to chloramphenicol, 27.5 % to erythromycin and 67.3 % to co
      trimoxazole. Of the 316 H. influenzae type b isolates, 44.0 % were ampicillin
      resistant, while only 13.1 % non-type b H. influenzae isolates were ampicillin
      resistant. Of the 229 ampicillin-resistant H. influenzae isolates, 196 (85.6 %)
      were positive for beta-lactamase; 93.4 % (214/229) were biotypes I, II and III,
      of which 49 % were biotype I, 27.9 % were type II and 16.6 % were type III. Most
      of the strains belonging to biotypes III-VIII were ampicillin sensitive.
      Ampicillin resistance is significantly more common in biotype I and serotype b
      than in other biotypes and serotypes.

PMID- 16434704
TI  - Virulence profile of strains of Cryptococcus neoformans var. grubii evaluated by
      experimental infection in BALB/c mice and correlation with exoenzyme activity.
AB  - To evaluate the virulence profile of strains of Cryptococcus neoformans var.
      grubii, 62 strains of this yeast were inoculated into BALB/c mice. It was found
      that 69 % of the strains were significantly more lethal to the mice and were
      recovered from a higher percentage (60 %) of the organs compared with the other
      31 % of the strains, which were recovered from 35 % of organs tested. Those
      strains that provoked higher death rates were also recovered from the central
      nervous system at a higher rate (84 %) than the less lethal strains (32 %). This
      finding led to an investigation of the factors that enhanced the capacity for
      neurological infection and death of the animals. The results of this study
      suggested that environmental strains present different degrees of virulence. The
      correlation of exoenzyme production before and after inoculation and between the
      groups of mice indicated that exoenzyme production had no influence on
      differences in virulence among the strains studied.

PMID- 16434705
TI  - Efficient resolution of Pneumocystis murina infection in surfactant protein A
      deficient mice following withdrawal of corticosteroid-induced immunosuppression.
AB  - Following withdrawal of immunosuppression, surfactant protein A (SP-A)-deficient
      and wild-type mice cleared Pneumocystis murina infection in a similar manner, but
      exhibited significant differences in lymphocyte populations, interleukin (IL)-6
      levels and chemokine expression levels. A higher percentage of lymphocytes were
      detected in lung lavage fluid from SP-A-deficient mice, but more CD4+ T cells
      were isolated from lung tissue of wild-type mice. Higher concentrations of IL-6
      were detected in lavage fluid and enhanced expression of lymphotactin and RANTES
      were detected in the lungs of wild-type mice. Equal levels of surfactant protein
      D were detected in SP-A-deficient and wild-type mice and no differences were
      detected in markers of lung injury between the two strains of mice. Thus, SP-A
      does not enhance organism clearance, but does modulate the host immune response
      during resolution of P. murina infection.

PMID- 16434706
TI  - Real-time detection of Mycoplasma pneumoniae in respiratory samples with an
      internal processing control.
AB  - Real-time PCR was employed to detect a region of the P1 cytadhesin gene of
      Mycoplasma pneumoniae in clinical samples. An internal processing control was
      included that could be co-amplified simultaneously in the same reaction tube. The
      assay could reproducibly detect 1 x 10(3) M. pneumoniae organisms ml(-1) in
      clinical samples. There was no amplification of DNA or signal production from 15
      other species of human mycoplasmas and 19 other bacterial species. Using a panel
      of 175 respiratory samples taken from patients with pneumonia of proven
      aetiology, the sensitivity was found to be 60 % and the specificity of the assay
      96.7 % when compared with serology. This assay is suitable for same-day diagnosis
      of M. pneumoniae infection and batch processing of respiratory samples for
      clinical screening.

PMID- 16434707
TI  - Characterization of group A streptococci (Streptococcus pyogenes): correlation of
      M-protein and emm-gene type with T-protein agglutination pattern and serum
      opacity factor.
AB  - Strain characterization of group A streptococci (GAS) has traditionally been
      based on serological identification of M protein. Additional tests to determine T
      protein serotype and production of streptococcal serum opacity factor (SOF)
      provide important information both to aid in and to supplement M-protein
      serotyping. Advances in DNA-sequencing technology in the late twentieth century
      resulted in the development of a method for determining the M type of GAS from
      the sequence of the gene encoding M protein, the emm gene. Although emm-sequence
      typing has largely replaced M typing in many laboratories, information provided
      by T typing and SOF determination continues to provide valuable supplementary
      information for strain characterization. A comprehensive summary of the
      correlation of T pattern and SOF production with M type was last published in
      1993, several years before emm typing became widely available. Since then, the
      ease of M-type identification afforded by emm typing has resulted in an increase
      in the number of confirmed M/emm types of more than 50 %. However, comprehensive
      information about T-protein serotype and the correlation of SOF production with
      these new M/emm types is not widely available. This report presents a
      comprehensive summary of this information, not only for newly described types,
      but also updated information for previously described types. This information was
      extracted from combined records from streptococcal reference laboratories at the
      University of Minnesota and at the Centers for Disease Control and Prevention in
      Atlanta. Data from more than 40,000 strains (representing uncomplicated GAS
      infections, systemic invasive infections and strains associated with non
      suppurative sequelae, collected from the US and diverse locations worldwide) were
      analysed.

PMID- 16434708
TI  - Multilocus sequence typing (MLST) analysis of Vibrio cholerae O1 El Tor isolates
      from Mozambique that harbour the classical CTX prophage.
AB  - Vibrio cholerae O1 isolates belonging to the Ogawa serotype, El Tor biotype,
      harbouring the classical CTX prophage were first isolated in Mozambique in 2004.
      Multilocus sequence typing (MLST) analysis using nine genetic loci showed that
      the Mozambique isolates have the same sequence type (ST) as O1 El Tor N16961, a
      representative of the current seventh cholera pandemic. Analysis of the CTX
      prophage in the Mozambique isolates indicated that there is one type of rstR in
      these isolates: the classical CTX prophage. It was also found that the ctxB-rstR
      rstA-rstB-phs-cep fragment was PCR-amplified from these isolates, which indicates
      the presence of a tandem repeat of the classical CTX prophage in the genome of
      the Mozambique isolates. The possible origin of these isolates and the presence
      of the tandem repeat of the classical prophage in them implicate the presence of
      the classical CTX phage.

PMID- 16434709
TI  - Serological diagnosis of Trypanosoma cruzi: evaluation of three enzyme
      immunoassays and an indirect immunofluorescent assay.
AB  - Chagas' disease is an important cause of heart failure in Latin America, but is
      rare in the United States. The immigration of persons from endemic countries
      increases the potential of encountering patients with the disease. Concerns have
      also been raised about the introduction of Trypanosoma cruzi, the parasite that
      causes the disease, into the blood supply and during organ transplantation. To
      compare Chagas' antibody tests that are available in the United States, we
      evaluated three IgG ELISAs, CeLLabs T. cruzi ELISA, Hemagen Chagas' kit and IVD
      Research Chagas' Serum Microwell ELISA, and MarDx indirect immunofluorescent
      assays. The CeLLabs and Hemagen IgG ELISAs had 100 % agreement, sensitivity and
      specificity. The IVD Research IgG ELISA had 94.6 % agreement, 100 % sensitivity
      and 93 % specificity.

PMID- 16434710
TI  - PCR detection of toxic shock syndrome toxin of Staphylococcus aureus from
      Tripoli, Libya.
AB  - Sixty-three Staphylococcus aureus strains (40 from clinical sources and 23 from
      food sources) were examined for toxic shock syndrome toxin-1 (TSST-1) using PCR,
      phage typed using the international phage set (IPS) and tested for their
      susceptibility to antibiotics. Only three strains (all from clinical sources)
      were positive for the TSST-1 gene (tst). The majority of S. aureus strains that
      were typeable by IPS belonged to group II. Resistance to one or more antibiotics
      was detected in 47.5 and 73.9 % of clinical and food strains, respectively. This
      is the first time that PCR detection of tst in S. aureus has been reported from
      Libya, and further studies are needed on the occurrence of toxic shock syndrome
      in the community and the role of TSST-1-producing S. aureus in this disease in
      Libya.

PMID- 16434711
TI  - Enterotoxicity and genetic variation among clinical Staphylococcus aureus
      isolates in Jordan.
AB  - A total of 100 Jordanian clinical Staphylococcus aureus isolates was analysed for
      the presence of the enterotoxin genes sea, seb, sec, sed and see using multiplex
      PCR. Twenty-three isolates (23 %) were potentially enterotoxigenic. The
      prevalence of sea, sec and sea plus sec among the total clinical isolates was 15,
      4 and 4 %, respectively. None of the isolates harboured sed, seb or see genes. S.
      aureus isolates were subjected to DNA fingerprinting by randomly amplified
      polymorphic DNA (RAPD) analysis to test whether isolates harbouring the toxin
      genes were genetically clustered. A total of 13 genotypes was identified at a 47
      % similarity level. Genotypes I and V accounted for the largest number of
      enterotoxigenic isolates (19 %). This study has demonstrated the genetic
      diversity of Jordanian clinical S. aureus isolates and shown that the presence of
      the toxin genes is not genotype specific.

PMID- 16434712
TI  - Differences in serological responses to specific glycopeptidolipid-core and
      common lipid antigens in patients with pulmonary disease due to Mycobacterium
      tuberculosis and Mycobacterium avium complex.
AB  - Disease due to the Mycobacterium avium complex (MAC) is one of the most important
      opportunistic pulmonary infections. Since the clinical features of MAC pulmonary
      disease and tuberculosis (TB) resemble each other, and the former is often
      difficult to treat with chemotherapy, early differential diagnosis is desirable.
      The humoral immune responses to both diseases were compared by a unique multiple
      antigen ELISA using mycobacterial species-common and species-specific lipid
      antigens, including glycopeptidolipid (GPL)-core. The results were assessed for
      two patient groups hospitalized and diagnosed clinically as having TB or MAC
      pulmonary disease. Diverse IgG antibody responsiveness was demonstrated against
      five lipid antigens: (1) monoacyl phosphatidylinositol dimannoside (Ac-PIM2), (2)
      cord factor (trehalose 6,6'-dimycolate) (TDM-T) and (3) trehalose monomycolate
      from Mycobacterium bovis Bacillus Calmette-Guerin (BCG) (TMM-T), and (4)
      trehalose monomycolate (TMM-M) and (5) GPL-core from MAC. Anti-GPL-core IgG
      antibody was critical, and detected only in the primary and the secondary MAC
      diseases with high positivity, up to 88.4 %. However, IgG antibodies against Ac
      PIM2, TDM-T and TMM-T were elevated in both TB and MAC patients. Anti-TMM-M IgG
      antibody was also elevated in MAC disease preferentially, with a positive rate of
      89.9 %, and therefore, it was also useful for the diagnosis of the disease. IgG
      antibody levels were increased at the early stages of the disease and declined in
      parallel to the decrease of bacterial burden to near the normal healthy control
      level, when the anti-mycobacterial chemotherapy was completed successfully.
      Unexpectedly, about 25 % of hospitalized TB patient sera were anti-GPL-core IgG
      antibody positive, although the specificity of GPL-core was sufficiently high
      (95.8 % negative in healthy controls), suggesting that a considerable number of
      cases of latent co-infection with MAC may exist in TB patients. Taken together,
      the combination of multiple-antigen ELISA using mycobacterial lipids, including
      GPL-core and TMM-M, gives good discrimination between healthy controls and sera
      from patients with TB or MAC disease, although for accurate diagnosis of TB more
      specific antigen(s) are needed.

PMID- 16434713
TI  - ent-Epiafzelechin-(4alpha-->8)-epiafzelechin extracted from Cassia javanica
      inhibits herpes simplex virus type 2 replication.
AB  - Herpes simplex virus (HSV) is a ubiquitous organism that causes infections in
      human populations throughout the world. It causes a variety of diseases ranging
      in severity from mild to life-threatening. In this study, ent-epiafzelechin
      (4alpha-->8)-epiafzelechin (EEE) extracted from the fresh leaves of Cassia
      javanica L. agnes de Wit (Leguminosae) was investigated for its in vitro anti-HSV
      2 activity using XTT and plaque reduction assays. Results showed that EEE
      inhibited HSV-2 replication in a dose-dependent manner. The IC50 value was 83.8
      +/- 10.9 and 166.8 +/- 12.9 microM for XTT and plaque reduction assays,
      respectively. EEE did not affect the viability and the proliferation of cells at
      antiviral concentrations. Mechanistic studies demonstrated that EEE prevented HSV
      2 from penetrating the cell and also interfered with HSV-2 replication at the
      late stage of its life cycle. It also disturbed virus attachment but the
      inhibitory effect was minor. In summary, the conclusion of this study was that
      EEE exhibits various modes of action in suppressing HSV-2 multiplication.

PMID- 16434714
TI  - Prevalence and association of PCR ribotypes of Clostridium difficile isolated
      from symptomatic patients from Warsaw with macrolide-lincosamide-streptogramin B
      (MLSB) type resistance.
AB  - Isolates (79 in total) of Clostridium difficile obtained over a 2 year period
      from 785 patients suspected of having C. difficile-associated diarrhoea (CDAD)
      and being hospitalized in the University Hospital in Warsaw were characterized by
      toxigenicity profile and PCR ribotyping. Furthermore, their susceptibility to
      clindamycin and erythromycin was determined. Among the 79 C. difficile isolates,
      35 were classified as (A+)B+, 1 as (A+)(B+)CDT+, 36 as (A-)B+ and 7 as (A-)B-. A
      total of 21 different PCR ribotypes was detected. Two main (A+)B+ strains
      circulated in our hospital: ribotype 014 and ribotype 046. Unexpectedly, the
      predominant PCR ribotype was type 017, a known (A-)B+ strain, and this accounted
      for about 45.5 % of all isolates cultured from patients with CDAD. Isolates
      belonging to PCR ribotype 017 were found in cases from epidemics of antibiotic
      associated diarrhoea in the internal and surgery units. High-level resistance
      (MIC > or = 256 mg l(-1)) to clindamycin and erythromycin was found in 39 (49 %)
      of the C. difficile isolates. Interestingly, 34 (94 %) of macrolide-lincosamide
      streptogramin B (MLSB) type resistance strains did not produce toxin A, but
      produced toxin B and were (A-)B+ ribotype 017. Thirty-seven of the high-level
      resistance strains harboured the erythromycin-resistance methylase gene (ermB).
      C. difficile isolates (2/29) that had high-level clindamycin and erythromycin
      resistance, and belonged to PCR ribotype 046, were ermB negative. These
      investigations revealed that the predominant C. difficile strain isolated from
      symptomatic patients hospitalized in University Hospital in Warsaw was MLSB
      positive clindamycin/erythromycin-resistant PCR ribotype 017.

PMID- 16434715
TI  - Pneumococcal surface protein A (PspA) family distribution among clinical isolates
      from adults over 50 years of age collected in seven countries.
AB  - The pneumococcal surface protein PspA, a cell-wall-associated surface protein, is
      a promising component for pneumococcal vaccines. In this study, the distribution
      of the PspA family was determined in a panel of invasive and clinically important
      pneumococcal isolates from adults over 50 years of age, collected between 1995
      and 2002. One thousand eight hundred and forty-seven recent isolates from
      invasive pneumococcal disease were obtained from seven Western countries,
      together with clinical data. An ELISA-based serological method was standardized
      in order to determine the PspA family and clade distribution. Molecular tests
      were used when isolates were non-typable by ELISA (PspA family typing by PCR).
      Only 42 (2.3 %) isolates were non-typable by ELISA and PspA family typing by PCR
      was performed. Finally, 3 isolates were considered as non-pneumococcal and 1844
      were classified as follows: 749 (40.6 %) were PspA family 1, 1078 (58.5 %) were
      PspA family 2, 13 (0.7 %) were PspA family 1 and 2 and 4 (0.2 %) remained non
      typable. The cross-reactivity of antibodies to PspAs of different clades was
      confirmed. In conclusion, inclusion of PspA family 1 and family 2 in future
      pneumococcal vaccines would ensure broad coverage of pneumococcal strains
      infecting people over 50 years of age.

PMID- 16434716
TI  - Predictive value of oral colonization by Candida yeasts for the onset of a
      nosocomial infection in elderly hospitalized patients.
AB  - The incidence of nosocomial yeast infections has increased markedly in recent
      decades, especially among the elderly. The present study was therefore initiated
      not only to determine the predictive value of oral colonization by yeasts for the
      onset of a nosocomial Candida infection in elderly hospitalized patients (> 65
      years), but also to clarify the factors that promote infection and to establish a
      relationship between the intensity of oral carriage and the onset of yeast
      infection. During this prospective cohort study, 256 patients (156 women and 100
      men with a mean age of 83 +/- 8 years) were surveyed for yeast colonization or
      infection. Samples were collected every 4 days from day 0 to day 16 from four
      sites in the mouth, and intrinsic and extrinsic factors that might promote
      infection were recorded for each patient. Pulsed field gel electrophoresis was
      performed on Candida albicans isolates from all infected patients. Poor
      nutritional status was observed in 81 % of the patients and hyposalivation in 41
      %. The colonization level was 67 % on day 0 (59 % C. albicans) and a heavy
      carriage of yeasts (> 50 c.f.u.) was observed for 51 % of the patients. The
      incidence of nosocomial colonization reached 6.9 % on day 4 (6.1 % on day 8 and
      2.7 % on day 12), and that of nosocomial infection was 3.7 % on day 4 (6.8 % on
      day 8, 11.3 % on day 12 and 19.2 % on day 16). Of the 35 patients infected, 57 %
      were suffering from oral candidiasis. The principal risk factors for colonization
      were a dental prosthesis, poor oral hygiene and the use of antibiotics. The risk
      factors for infection, in addition to those already mentioned for colonization,
      were endocrine disease, poor nutritional status, prolonged hospitalization and
      high colony counts. Genotyping revealed person-to-person transmission in two
      patients. Thus, this study demonstrates a significant association between oral
      colonization and the onset of yeast infections in elderly hospitalized patients.
      Therefore, oral samples should be collected at admission and antifungal treatment
      should be administered in cases of colonization, especially in patients
      presenting a heavy carriage of yeasts. Genotyping of the strains confirmed the
      possibility of person-to-person transmission.

PMID- 16434717
TI  - Experimental model of infection with non-toxigenic strains of Corynebacterium
      diphtheriae and development of septic arthritis.
AB  - Corynebacterium diphtheriae is a well-known cause of localized respiratory tract
      infections. However, this micro-organism can also be associated with invasive
      infections, such as endocarditis, septic arthritis and osteomyelitis. Invasive
      infections are often caused by non-toxigenic strains. To set up an in vivo
      experimental model of C. diphtheriae infection, mice were infected intravenously
      with different doses (ranging from 1 x 10(7) to 5 x 10(8) bacteria per mouse) of
      three non-toxigenic strains, namely ISS-4749, ISS-4746 and ISS-3319. Similar
      mortality rates were observed with the three strains, with an LD50 ranging from 9
      x 10(7) to 1.2 x 10(8). All strains were arthritogenic, although to different
      extents. ISS-4749 and ISS-4746 infection resulted in a maximum of 60 and 50 %,
      respectively, of animals with articular lesions, while in the ISS-3319-infected
      group only 25 % were positive. There were differences in systemic and joint
      cytokine production in the three experimental groups. ISS-4749- and ISS-4746
      infected mice exhibited higher local levels of interleukin (IL)-6 and IL-1beta
      than ISS-3319-infected animals. At systemic levels, ISS-3319 was able to induce
      early and sustained production of interferon-gamma (IFN-gamma), but not IL-6.
      Conversely, infection with the other strains resulted in high IL-6, but not IFN
      gamma, production. In conclusion, an experimental model of C. diphtheriae
      infection was set up, with development of septic arthritis. This model could be
      useful in studies on the pathogenicity and characterization of virulence factors
      other than toxin production.

PMID- 16434718
TI  - Kodamaea (Pichia) ohmeri fungaemia in a premature neonate.
AB  - Kodamaea ohmeri is a yeast that rarely causes human infections. The first case of
      K. ohmeri fungaemia in a premature neonate is reported; it was successfully
      treated with liposomal amphotericin B. Biochemical identification of the yeast
      was performed by Vitek II and API and was confirmed by rRNA gene sequencing. K.
      ohmeri as a human pathogenic yeast is uncommon to hospitalized neonates and
      immunocompromised individuals.

PMID- 16434719
TI  - Aeromonas veronii biovar sobria bacteraemia with septic arthritis confirmed by
      16S rDNA PCR in an immunocompetent adult.
AB  - An 81-year-old man developed septic arthritis and bacteraemia with Aeromonas
      veronii biovar sobria. Cultures of the joint wash-out fluid were negative;
      however, DNA matching that of Aeromonas veronii was identified by 16S rDNA PCR.
      The patient was successfully treated with a 4 week course of ciprofloxacin. No
      recognized risk factors were found.

PMID- 16434720
TI  - Use of urine samples as controls for treatment of a Chlamydia trachomatis
      infection.

PMID- 16434721
TI  - Identical Burkholderia cepacia complex strain types isolated from multiple
      patients attending a hospital in Brazil.

PMID- 16434722
TI  - Magnesium and arterial stiffness.

PMID- 16434723
TI  - Mononuclear leukocyte mineralocorticoid receptors. A possible link between
      aldosterone and atherosclerosis.

PMID- 16434724
TI  - Dietary approaches to prevent and treat hypertension: a scientific statement from
      the American Heart Association.
AB  - A substantial body of evidence strongly supports the concept that multiple
      dietary factors affect blood pressure (BP). Well-established dietary
      modifications that lower BP are reduced salt intake, weight loss, and moderation
      of alcohol consumption (among those who drink). Over the past decade, increased
      potassium intake and consumption of dietary patterns based on the "DASH diet"
      have emerged as effective strategies that also lower BP. Of substantial public
      health relevance are findings related to blacks and older individuals.
      Specifically, blacks are especially sensitive to the BP-lowering effects of
      reduced salt intake, increased potassium intake, and the DASH diet. Furthermore,
      it is well documented that older individuals, a group at high risk for BP-related
      cardiovascular and renal diseases, can make and sustain dietary changes. The risk
      of cardiovascular disease increases progressively throughout the range of BP,
      beginning at 115/75 mm Hg. In view of the continuing epidemic of BP-related
      diseases and the increasing prevalence of hypertension, efforts to reduce BP in
      both nonhypertensive and hypertensive individuals are warranted. In
      nonhypertensive individuals, dietary changes can lower BP and prevent
      hypertension. In uncomplicated stage I hypertension (systolic BP of 140 to 159 mm
      Hg or diastolic BP of 90 to 99 mm Hg), dietary changes serve as initial treatment
      before drug therapy. In those hypertensive patients already on drug therapy,
      lifestyle modifications, particularly a reduced salt intake, can further lower
      BP. The current challenge to healthcare providers, researchers, government
      officials, and the general public is developing and implementing effective
      clinical and public health strategies that lead to sustained dietary changes
      among individuals and more broadly among whole populations.

PMID- 16434725
TI  - Endothelin action on pituitary lactotrophs: one receptor, many GTP-binding
      proteins.
AB  - The endothelins are a family of hormones that have a biphasic action on pituitary
      lactotrophs. The initial effect is stimulatory, followed later by inhibition that
      persists long after the agonist has been removed. Recent research has uncovered
      several G protein pathways that mediate these effects.

PMID- 16434726
TI  - A tale of two signals: Wnt and Hedgehog in dentate neurogenesis.
AB  - It is now widely accepted that discrete regions of the adult brain contain stem
      cells that continue to generate new neurons. However, it remains unclear what
      molecular signals define the neurogenic niche and how such signals act on the
      heterogeneous cell populations within these regions. Here we discuss two recent
      studies that demonstrate the role of Wnt and Sonic Hedgehog signaling in
      neurogenic zones. Wnts act on neuronal precursors that mature and contribute to
      the dentate gyrus (DG), whereas Sonic Hedgehog affects the bona fide stem cells
      and transit amplifying cells (the partially committed progeny of stem cells).
      These studies further define how discrete populations of cells react to specific
      extracellular signals provided within the neurogenic niche to survive,
      proliferate, and form functional mature cell types.

PMID- 16434727
TI  - Can systemic diseases co-induce (not just exacerbate) periodontitis? A
      hypothetical "two-hit" model.

PMID- 16434728
TI  - Innate immune signaling and Porphyromonas gingivalis-accelerated atherosclerosis.
AB  - Periodontal diseases are a group of diseases that lead to erosion of the hard and
      soft tissues of the periodontium, which, in severe cases, can result in tooth
      loss. Anecdotal clinical observations have suggested that poor oral health may be
      associated with poor systemic health; however, only recently have appropriate
      epidemiological studies been initiated, with defined clinical endpoints of
      periodontal disease, to address the association of periodontal disease with
      increased risk for cardiovascular and cerebrovascular disease. Although
      conflicting reports exist, these epidemiological studies support this connection.
      Paralleling these epidemiological studies, emerging basic scientific studies also
      support that infection may represent a risk factor for atherosclerosis. With P.
      gingivalis as a model pathogen, in vitro studies support that this organism can
      activate host innate immune responses associated with atherosclerosis, and in
      vivo studies demonstrate that this organism can accelerate atheroma deposition in
      animal models. In this review, we focus primarily on the basic scientific studies
      performed to date which support that infection with bacteria, most notably P.
      gingivalis, accelerates atherosclerosis. Furthermore, we attempt to bring
      together these studies to provide an up-to-date framework of emerging theories
      into the mechanisms underlying periodontal disease and increased risk for
      atherosclerosis, as well as identify intervention strategies to reduce the
      incidence of periodontal disease in humans, in an attempt to decrease risk for
      systemic complications of periodontal disease such as atherosclerotic
      cardiovascular disease.

PMID- 16434729
TI  - The role of heparan sulfate and perlecan in bone-regenerative procedures.
AB  - Tissue engineering, grafting procedures, regeneration, and tissue remodeling are
      developing therapeutic modalities with great potential medical value, but these
      regenerative modalities are not as effective or predictable as clinicians and
      patients would like. Greater understanding of growth factors, cytokines,
      extracellular matrix molecules, and their roles in cell-mediated healing
      processes have made these regenerative therapies more clinically viable and will
      continue advancing the fields of tissue engineering and grafting. However,
      millions of oral and non-oral bone-grafting procedures are performed annually,
      and only a small percentage yield the most desirable results. Here we review the
      heparan-sulfate-decorated extracellular biomolecule named perlecan and the
      research relating to its potential as an adjunct in bone-regenerative procedures.
      The review includes an overview of bone graft substitutes and biological adjuncts
      to bone-regenerative procedures in medicine as they apply to periodontal disease,
      alveolar ridge augmentation, and barrier membrane therapy. Perlecan is discussed
      as a potential biological adjunct in terms of growth factor sequestration and
      delivery, and promoting cell adhesion, proliferation, differentiation, and
      angiogenesis. Further, we propose delivery and application schemes for perlecan
      and/or its domains in bone-regenerative procedures, with particular emphasis on
      its heparan-sulfate-decorated domain I. The perlecan molecule, with its heparan
      sulfate glycosylation, may provide a multi-faceted approach for the delivery of a
      more comprehensive stimulus than other single potential adjuncts currently
      available for bone-regenerative procedures.

PMID- 16434730
TI  - Reduced antigenicity of type I collagen and proteoglycans in sclerotic dentin.
AB  - Antigenic alterations to the dentin organic matrix may be detected by an
      immunohistochemical approach. We hypothesized that alterations in the
      antigenicity of type I collagen and proteoglycans occur in sclerotic dentin under
      caries lesions. Transverse sections were prepared from carious teeth in the
      sclerotic zone and normal hard dentin. A double-immunolabeling technique was
      performed on these sections, with anti-type I collagen and anti-chondroitin 4/6
      sulfate monoclonal primary antibodies. We used gold-conjugated secondary
      antibodies to visualize the distribution of intact collagen fibrils and
      proteoglycans by high-resolution SEM. For sclerotic dentin, labeling densities
      were 19.57 +/- 3.01/microm2 for collagen and 9.84 +/- 2.62/microm2 for
      proteoglycans. For normal hard dentin, values were 35.20 +/- 2.73/microm2 and
      17.03 +/- 1.98/microm2, respectively. Distribution of intact collagen fibrils and
      proteoglycans in sclerotic dentin was significantly lower than in normal hard
      dentin. Reductions in antigenicity from the organic matrix of sclerotic dentin
      under caries lesions raise concern about the potential of intrafibrillar
      remineralization.

PMID- 16434731
TI  - Cloning, sequencing, and expression of the amelogenin gene in two scincid
      lizards.
AB  - Our knowledge of the gene coding for amelogenin, the major enamel protein, is
      mainly based on mammalian sequences. Only two sequences are available in
      reptiles. To know whether the snake sequence is representative of the amelogenin
      condition in squamates, we have studied amelogenin in two scincid lizards. Lizard
      amelogenin possesses numerous conserved residues in the N- and C-terminal
      regions, but its central region is highly variable, even when compared with the
      snake sequence. This rapid evolution rate indicates that a single squamate
      sequence was not representative, and that comparative studies of reptilian
      amelogenins might be useful to detect the residues which are really important for
      amelogenin structure and function. Reptilian and mammalian enamel structure is
      roughly similar, but no data support amelogenin being similarly expressed during
      amelogenesis. By performing in situ hybridization using a specific probe, we
      showed that lizard ameloblasts express amelogenin as described during mammalian
      amelogenesis. However, we have not found amelogenin transcripts in odontoblasts.
      This indicates that full-length amelogenin is specific to enamel matrix, at least
      in this lizard.

PMID- 16434733
TI  - Differential uPA expression by TGF-beta1 in gingival fibroblasts.
AB  - Transforming Growth Factor-beta1 (TGF-beta1) plays a key role in connective
      tissue remodeling and inflammation. Under pathological conditions, like
      periodontal disease, fibroblasts may display an altered response to this growth
      factor. To investigate this question, we have studied whether TGF-beta1 may
      differentially regulate the expression of urokinase at the protein level in
      primary cultures of fibroblasts derived from healthy gingiva, granulation tissue
      from gingival wounds, and chronic periodontal disease. We observed that TGF-beta1
      may repress urokinase expression in healthy gingival fibroblasts and promote its
      production in granulation-tissue fibroblasts. A significant correlation was found
      between expression of the myofibroblast marker alpha-smooth-muscle actin and
      stimulation of urokinase production by TGF-beta1. Immunostaining of gingival
      wounds showed that myofibroblasts were involved in urokinase production. TGF
      beta1-stimulated urokinase expression was blocked after inhibition of the c-jun
      NH2 terminal kinase signaling pathway. We propose that stimulation of urokinase
      production by TGF-beta1 is involved in the responses of activated fibroblasts to
      tissue injury.

PMID- 16434732
TI  - Amelogenin-mediated regulation of osteoclastogenesis, and periodontal cell
      proliferation and migration.
AB  - We previously reported that amelogenin isoforms M180 and leucine-rich amelogenin
      peptide (LRAP) are expressed in the periodontal region, and that their absence is
      associated with increased cementum defects in amelogenin-knockout (KO) mice. The
      aim of the present study was to characterize the functions of these isoforms in
      osteoclastogenesis and in the proliferation and migration of
      cementoblast/periodontal ligament cells. The co-cultures of wild-type (WT)
      osteoclast progenitor and KO cementoblast/periodontal ligament cells displayed
      more tartrate-resistant acid phosphatase (TRAP)-positive cells than the co
      cultures of WT cells. The addition of LRAP to both co-cultures significantly
      reduced RANKL expression and the TRAP-positive cells. Proliferation and migration
      rates of the KO cementoblast/periodontal ligament cells were lower than those of
      WT cells and increased with the addition of either LRAP or P172 (a porcine
      homolog of mouse M180). Thus, we demonstrate the regulation of osteoclastogenesis
      by LRAP, and the proliferation and migration of cementoblast/periodontal ligament
      cells by LRAP and P172.

PMID- 16434734
TI  - Rosiglitazone reduces the evolution of experimental periodontitis in the rat.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptor
      appears to play a pivotal role in the regulation of cellular proliferation and
      inflammation. Recent evidence also suggests that rosiglitazone, a PPAR-gamma
      agonist, reduces acute and chronic inflammation. We hypothesized that
      rosiglitazone would attenuate periodontal inflammation. In the present study, we
      investigated the effects of rosiglitazone in a rat model of ligature-induced
      periodontitis. At day 8, ligation significantly induced an increase in neutrophil
      infiltration, as well as of gingivomucosal tissue expression of iNOS,
      nitrotyrosine formation, and poly (ADP-ribose) polymerase activation. Ligation
      significantly increased Evans blue extravasation in gingivomucosal tissue and
      alveolar bone destruction. Intraperitoneal injection of rosiglitazone (10 mg/kg
      10% DMSO daily for 8 days) significantly decreased all of the parameters of
      inflammation, as described above. Analysis of these data demonstrated that
      rosiglitazone exerted an anti-inflammatory role during experimental
      periodontitis, and was able to ameliorate the tissue damage associated with
      ligature-induced periodontitis.

PMID- 16434735
TI  - Articaine is more effective than lidocaine or mepivacaine in rat sensory nerve
      conduction block in vitro.
AB  - The reasons for the relatively high failure rate after inferior alveolar nerve
      block in dentistry are not fully understood. Therefore, the effectiveness of
      different anesthetic solutions (2% and 4% lidocaine, 3% mepivacine, 2% and 4%
      articaine) in depressing the compound action potential amplitude of the sensory
      fibers in the rat sural nerve was examined under strictly controlled conditions
      in vitro. After application of an anesthetic solution and stimulation of the
      nerve with a supramaximal electrical stimulus, a complete disappearance of the
      compound action potential of the C fibers, but not of the A fibers, was observed
      in all the experimental groups. Both 2% and 4% articaine more effectively
      depressed the compound action potential of the A fibers than did other anesthetic
      solutions. These results are discussed in the light of recent clinical reports
      finding no differences in the effectiveness between 4% articaine and 2% lidocaine
      regarding the inferior alveolar nerve block.

PMID- 16434736
TI  - Origin of the deciduous upper lateral incisor and its clinical aspects.
AB  - The upper lateral incisor in humans is often affected by dental anomalies that
      might be explained developmentally. To address this question, we investigated the
      origin of the deciduous upper lateral incisor (i2) in normal human embryos at
      prenatal weeks 6-8. We used serial frontal histological sections and computer
      aided 3D reconstructions. At embryonic days 40-42, two thickenings of the dental
      epithelia in an "end-to-end" orientation were separated by a groove at the former
      fusion site of the medial nasal and maxillary processes. Later, these dental
      epithelia fused, forming a continuous dental lamina. At the fusion site, i2
      started to develop. The fusion line was detectable on the i2 germ until the 8th
      prenatal week. The composite origin of the i2 may be associated with its
      developmental vulnerability. From a clinical aspect, a supernumerary i2 might be
      a form of cleft caused by a non-fusion of the dental epithelia.

PMID- 16434738
TI  - Mutans streptococci dose response to xylitol chewing gum.
AB  - Xylitol is promoted in caries-preventive strategies, yet its effective dose range
      is unclear. This study determined the dose-response of mutans streptococci in
      plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were
      randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol
      3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4
      times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on
      modified Mitis Salivarius agar for mutans streptococci and on blood agar for
      total culturable flora. At 5 wks, mutans streptococci levels in plaque were 10x
      lower than baseline in G3 and G4 (P = 0.007/0.003). There were no differences in
      saliva. At 6 mos, mutans streptococci in plaque for G3 and G4 remained 10x lower
      than baseline (P = 0.007/0.04). Saliva for G3 and G4 was lower than baseline by 8
      to 9x (P = 0.011/0.038). Xylitol at 6.44 g/day and 10.32 g/day reduces mutans
      streptococci in plaque at 5 wks, and in plaque and unstimulated saliva at 6 mos.
      A plateau effect is suggested between 6.44 g and 10.32 g xylitol/day.

PMID- 16434737
TI  - Fluoride varnish efficacy in preventing early childhood caries.
AB  - To determine the efficacy of fluoride varnish (5% NaF, Duraphat, Colgate) added
      to caregiver counseling to prevent early childhood caries, we conducted a two
      year randomized, dental-examiner-masked clinical trial. Initially, 376 caries
      free children, from low-income Chinese or Hispanic San Francisco families, were
      enrolled (mean age +/- standard deviation, 1.8 +/- 0.6 yrs). All families
      received counseling, and children were randomized to the following groups: no
      fluoride varnish, fluoride varnish once/year, or fluoride varnish twice/year. An
      unexpected protocol deviation resulted in some children receiving less active
      fluoride varnish than assigned. Intent-to-treat analyses showed a fluoride
      varnish protective effect in caries incidence, p < 0.01. Analyzing the number of
      actual, active fluoride varnish applications received resulted in a dose-response
      effect, p < 0.01. Caries incidence was higher for 'counseling only' vs.
      'counseling + fluoride varnish assigned once/year' (OR = 2.20, 95% CI 1.19-4.08)
      and 'twice/year' (OR = 3.77, 95% CI 1.88-7.58). No related adverse events were
      reported. Fluoride varnish added to caregiver counseling is efficacious in
      reducing early childhood caries incidence.

PMID- 16434740
TI  - Coordination of tongue pressure and jaw movement in mastication.
AB  - The tongue plays an important role in mastication and swallowing by its contact
      with the hard palate. Using an experimental palatal plate with 7 pressure
      sensors, and recording jaw movement using mandibular kinesiography, we assessed,
      in healthy subjects, the coordination of tongue and jaw movements during the
      entire masticatory sequence of solids, by measuring tongue pressure against the
      hard palate. Tongue pressure appeared during the occlusal phase, reached a peak
      near the start of opening, and disappeared during opening. Specific patterns in
      order, duration, and magnitude of tongue pressure were seen at the 7 pressure
      sensors in each chewing stroke. Magnitude and duration were significantly larger
      in the late stage of chewing (8 strokes before initial swallowing) than in the
      early stage (until 8 strokes after starting mastication). The normal pattern of
      tongue contact against the hard palate, control of tongue activity, and
      coordination with jaw movement during mastication is described.

PMID- 16434739
TI  - The transmission of anaerobic periodontopathic organisms.
AB  - The oral microbial flora is unique, and available evidence indicates that it is
      passed vertically from parents to children. In this investigation, we used a
      chairside assay for the N-benzoyl-DL-arginine-2-naphthylamide (BANA)-sensitive
      enzyme found in Porphyromonas gingivalis, Treponema denticola, and Tannerella
      forsythensis, to determine the prevalence of these BANA-positive species in young
      children and their caregivers. We predicted that if the BANA enzyme was found in
      plaque samples of children, it would also be present in the plaque samples of the
      caregivers. Forty-four percent of 150 children had at least one plaque sample
      positive for the BANA enzyme. If the caregiver was BANA-positive, the odds of the
      child also being BANA-positive was 35 times more than for a child with a BANA
      negative caregiver, after adjustment for the child's age and papillary bleeding
      score (PBS). Other significant predictors were the PBS of children (p < 0.001), a
      history of periodontal disease, and the ages of the caregivers (p < 0.001).

PMID- 16434741
TI  - Prevention of amyloid fibril formation of amyloidogenic chicken cystatin by site
      specific glycosylation in yeast.
AB  - To address the role of glycosylation on fibrillogenicity of amyloidogenic chicken
      cystatin, the consensus sequence for N-linked glycosylation (Asn106-Ile108 -->
      Asn106-Thr108) was introduced by site-directed mutagenesis into the wild-type and
      amyloidogenic chicken cystatins to construct the glycosylated form of chicken
      cystatins. Both the glycosylated and unglycosylated forms of wild-type and
      amyloidogenic mutant I66Q cystatin were expressed and secreted in a culture
      medium of yeast Pichia pastoris transformants. Comparison of the amount of
      insoluble aggregate, the secondary structure, and fibrillogenicity has shown that
      the N-linked glycosylation could prevent amyloid fibril formation of
      amyloidogenic chicken cystatin secreted in yeast cells without affecting its
      inhibitory activities. Further study showed this glycosylation could inhibit the
      formation of cystatin dimers. Therefore, our data strongly suggested that the
      mechanism causing the prevention of amyloidogenic cystation fibril formation may
      be realized through suppression of the formation of three-dimensional domain
      swapped dimers and oligomers of amyloidogenic cystatin by the glycosylated chains
      at position 106.

PMID- 16434742
TI  - The redox couple of the cytochrome c cyanide complex: the contribution of heme
      iron ligation to the structural stability, chemical reactivity, and physiological
      behavior of horse cytochrome c.
AB  - Contrary to most heme proteins, ferrous cytochrome c does not bind ligands such
      as cyanide and CO. In order to quantify this observation, the redox potential of
      the ferric/ferrous cytochrome c-cyanide redox couple was determined for the first
      time by cyclic voltammetry. Its E0' was -240 mV versus SHE, equivalent to -23.2
      kJ/mol. The entropy of reaction for the reduction of the cyanide complex was also
      determined. From a thermodynamic cycle that included this new value for the cyt c
      cyanide complex E0', the binding constant of cyanide to the reduced protein was
      estimated to be 4.7 x 10(-3) L M(-1) or 13.4 kJ/mol (3.2 kcal/mol), which is 48.1
      kJ/mol (11.5 kcal/mol) less favorable than the binding of cyanide to
      ferricytochrome c. For coordination of cyanide to ferrocytochrome c, the entropy
      change was earlier experimentally evaluated as 92.4 J mol(-1) K(-1) (22.1 e.u.)
      at 25 K, and the enthalpy change for the same net reaction was calculated to be
      41.0 kJ/mol (9.8 kcal/mol). By taking these results into account, it was
      discovered that the major obstacle to cyanide coordination to ferrocytochrome c
      is enthalpic, due to the greater compactness of the reduced molecule or,
      alternatively, to a lower rate of conformational fluctuation caused by solvation,
      electrostatic, and structural factors. The biophysical consequences of the large
      difference in the stabilities of the closed crevice structures are discussed.

PMID- 16434743
TI  - Determination of network of residues that regulate allostery in protein families
      using sequence analysis.
AB  - Allosteric interactions between residues that are spatially apart and well
      separated in sequence are important in the function of multimeric proteins as
      well as single-domain proteins. This observation suggests that, among the
      residues that are involved in long-range communications, mutation at one site
      should affect interactions at a distant site. By adopting a sequence-based
      approach, we present an automated approach that uses a generalization of the
      familiar sequence entropy in conjunction with a coupled two-way clustering
      algorithm, to predict the network of interactions that trigger allosteric
      interactions in proteins. We use the method to identify the subset of dynamically
      important residues in three families, namely, the small PDZ family, G protein
      coupled receptors (GPCR), and the Lectins, which are cell-adhesion receptors that
      mediate the tethering and rolling of leukocytes on inflamed endothelium. For the
      PDZ and GPCR families, our procedure predicts, in agreement with previous
      studies, a network containing a small number of residues that are involved in
      their function. Application to the Lectin family reveals a network of residues
      interspersed throughout the C-terminal end of the structure that are responsible
      for binding to ligands. Based on our results and previous studies, we propose
      that functional robustness requires that only a small subset of distantly
      connected residues be involved in transmitting allosteric signals in proteins.

PMID- 16434744
TI  - Crystal structural analysis and metal-dependent stability and activity studies of
      the ColE7 endonuclease domain in complex with DNA/Zn2+ or inhibitor/Ni2+.
AB  - The nuclease domain of ColE7 (N-ColE7) contains an H-N-H motif that folds in a
      beta beta alpha-metal topology. Here we report the crystal structures of a Zn2+
      bound N-ColE7 (H545E mutant) in complex with a 12-bp duplex DNA and a Ni2+-bound
      N-ColE7 in complex with the inhibitor Im7 at a resolution of 2.5 A and 2.0 A,
      respectively. Metal-dependent cleavage assays showed that N-ColE7 cleaves double
      stranded DNA with a single metal ion cofactor, Ni2+, Mg2+, Mn2+, and Zn2+. ColE7
      purified from Escherichia coli contains an endogenous zinc ion that was not
      replaced by Mg2+ at concentrations of <25 mM, indicating that zinc is the
      physiologically relevant metal ion in N-ColE7 in host E. coli. In the crystal
      structure of N-ColE7/DNA complex, the zinc ion is directly coordinated to three
      histidines and the DNA scissile phosphate in a tetrahedral geometry. In contrast,
      Ni2+ is bound in N-ColE7 in two different modes, to four ligands (three
      histidines and one phosphate ion), or to five ligands with an additional water
      molecule. These data suggest that the divalent metal ion in the His-metal finger
      motif can be coordinated to six ligands, such as Mg2+ in I-PpoI, Serratia
      nuclease and Vvn, five ligands or four ligands, such as Ni2+ or Zn2+ in ColE7.
      Universally, the metal ion in the His-metal finger motif is bound to the DNA
      scissile phosphate and serves three roles during hydrolysis: polarization of the
      P-O bond for nucleophilic attack, stabilization of the phosphoanion transition
      state and stabilization of the cleaved product.

PMID- 16434745
TI  - Context-dependent mutations predominate in an engineered high-affinity single
      chain antibody fragment.
AB  - A mutational analysis of the femtomolar-affinity anti-fluorescein antibody 4M5.3,
      compared to its wild-type progenitor, 4-4-20, indicates both context-dependent
      and -independent mutations are responsible for the 1800-fold affinity
      improvement. 4M5.3 was engineered from 4-4-20 by directed evolution and contains
      14 mutations. The seven mutations identified as present in each of 10 final round
      affinity maturation clones were studied here. Affinities of the 4-4-20 single
      mutant addition and 4M5.3 single site reversion mutants were compared. These
      experiments identified four mutations, of these seven, that were context
      dependent in their contribution to higher affinity. A simplified mutant
      containing only these seven mutations was created to analyze complete double
      mutant cycles of selected sets of mutations. Specific mutational sets studied
      included the ligand contact mutations, the heavy chain CDR3 mutations, the heavy
      chain CDR3 mutations plus the neighboring residue at site H108, and the early and
      late acquired mutations on the directed evolution pathway. The heavy chain CDR3
      mutational set and the ligand-contacting mutations were shown to provide -1.4 and
      -2.0 kcal/mol, respectively, of the total -3.5 kcal/mol change in free energy of
      binding of the seven-site consensus mutant. The mutations acquired late in the
      directed evolution rounds provided much of the change in free energy without the
      earlier acquired mutations (-3.1 kcal/mol of the total -3.5 kcal/mol). Prior
      structural data and electrostatic calculations presented several hypotheses for
      the higher affinity contributions, some of which are supported by these
      mutational data.

PMID- 16434746
TI  - Photonic activation of disulfide bridges achieves oriented protein immobilization
      on biosensor surfaces.
AB  - Photonic induced immobilization is a novel technology that results in spatially
      oriented and spatially localized covalent coupling of biomolecules onto thiol
      reactive surfaces. Immobilization using this technology has been achieved for a
      wide selection of proteins, such as hydrolytic enzymes (lipases/esterases,
      lysozyme), proteases (human plasminogen), alkaline phosphatase, immunoglobulins'
      Fab fragment (e.g., antibody against PSA [prostate specific antigen]), Major
      Histocompability Complex class I protein, pepsin, and trypsin. The reaction
      mechanism behind the reported new technology involves "photonic activation of
      disulfide bridges," i.e., light-induced breakage of disulfide bridges in proteins
      upon UV illumination of nearby aromatic amino acids, resulting in the formation
      of free, reactive thiol groups that will form covalent bonds with thiol-reactive
      surfaces (see Fig. 1). Interestingly, the spatial proximity of aromatic residues
      and disulfide bridges in proteins has been preserved throughout molecular
      evolution. The new photonic-induced method for immobilization of proteins
      preserves the native structural and functional properties of the immobilized
      protein, avoiding the use of one or more chemical/thermal steps. This technology
      allows for the creation of spatially oriented as well as spatially defined
      multiprotein/DNA high-density sensor arrays with spot size of 1 microm or less,
      and has clear potential for biomedical, bioelectronic, nanotechnology, and
      therapeutic applications.

PMID- 16434748
TI  - What have we really learned from SARS?

PMID- 16434747
TI  - Variation of loop sequence alters stability of cytolethal distending toxin (CDT):
      crystal structure of CDT from Actinobacillus actinomycetemcomitans.
AB  - Cytolethal distending toxin (CDT) secreted by Actinobacillus
      actinomycetemcomitans induces cell cycle arrest of cultured cells in the G2
      phase. The crystal structure of the natural form of A. actinomycetemcomitans DCT
      (aCDT) has been determined at 2.4 A resolution. aCDT is a heterotrimer consisting
      of the three subunits, aCdtA, aCdtB, and aCdtC. Two crystallographically
      independent aCDTs form a dimer through interactions of the aCdtB subunits. The
      primary structure of aCDT has 94.3% identity with that of Haemophilus ducreyi CDT
      (hCDT), and the structure of aCDT is quite similar to that of hCDT reconstituted
      from the three subunits determined recently. However, the molecular packings in
      the crystal structures of aCDT and hCDT are quite different. A careful analysis
      of molecular packing suggests that variation of the amino acid residues in a
      nonconserved loop (181TSSPSSPERRGY192 of aCdtB and 181NSSSSPPERRVY192 of hCdtB)
      is responsible for the different oligomerization of very similar CDTs. The loop
      of aCdtB has a conformation to form a dimer, while the loop conformation of hCdtB
      prevents hCDT from forming a dimer. Although dimerization of aCDT does not affect
      toxic activity, it changes the stability of protein. aCDT rapidly aggregates and
      loses toxic activity in the absence of sucrose in a buffered solution, while hCDT
      is stable and retains toxic activity. Another analysis of crystal structures of
      aCDT and hCDT suggests that the receptor contact area is in the deep groove
      between CdtA and CdtC, and the characteristic "aromatic patch" on CdtA.

PMID- 16434749
TI  - Hemodynamic effects of central neural blockade in elderly patients.

PMID- 16434751
TI  - Comparison of phonomyography, kinemyography and mechanomyography for
      neuromuscular monitoring.
AB  - PURPOSE: The gold standard of neuromuscular monitoring is mechanomyography (MMG).
      Phonomyography (PMG) and kinemyography (KMG) are new methods of neuromuscular
      monitoring. In this study, all three methods were compared to determine
      neuromuscular blockade at the adductor pollicis muscle. METHODS: In 14 patients,
      phonomyography was recorded via a microphone taped to the thenar region. A
      standard mechanomyographic device was applied to the same thumb, and attached to
      the force transducer. On the contralateral side, a NMT-Mechanosensor(R) probe was
      attached to the thumb and forefinger (KMG). After induction of general
      anaesthesia, the ulnar nerves were stimulated supramaximally using superficial
      electrodes at the wrists using train-of-four (TOF) stimulation every 12 sec.
      Onset and recovery indices measured by the three methods after mivacurium 0.2 mg
      x kg(-1) iv were compared using ANOVA-multiple group comparisons. Agreement
      between methods was determined using Lin's concordance correlation coefficient.
      RESULTS: Onset time and peak effect measured via MMG and PMG were similar.
      Recovery times from neuromuscular blockade (NMB) as measured via the three
      methods were not different. Agreement between PMG and MMG was excellent for onset
      and offset of NMB but unsatisfactory for peak effect. Agreement between MMG and
      KMG was satisfactory for TOF 0.25 and 0.50, and excellent for TOF 0.75 and 0.90
      (onset and peak effect not determined for KMG). Agreement between PMG and KMG was
      satisfactory for TOF 0.25, 0.50 and 0.75, and excellent for TOF 0.90. CONCLUSION:
      Mechanomyography, PMG and KMG show satisfactory agreement for determination of
      recovery of NMB for clinical purposes.

PMID- 16434750
TI  - Intubation of SARS patients: infection and perspectives of healthcare workers.
AB  - PURPOSE: The outbreak of severe acute respiratory syndrome (SARS) in 2003
      presented major challenges to the safety of anesthesiologists and other
      healthcare workers (HCWs). This study determined the incidence of SARS
      transmission to HCWs who intubated patients and analyzed the concerns of HCWs
      regarding personal and patient safety. METHODS: Healthcare workers who performed
      tracheal intubation in 10 Toronto hospitals were identified using the Ontario
      Public Health database. A questionnaire was used to collect information from the
      HCWs. To determine if the patterns of personal protection or concerns changed
      over time, data were analyzed according to whether the intubation occurred during
      SARS 1 (February 23 to April 21) or SARS 2 (April 22 to July 1). RESULTS: Thirty
      three HCWs who performed 39 intubations on 35 SARS patients were interviewed.
      Three of 23 HCWs (13%) acquired SARS during SARS 1 whereas none (0/10) acquired
      SARS during SARS 2. Personal protection increased from SARS 1 to SARS 2 and HCWs'
      concerns changed over time. During SARS 1, concerns focused on the need for
      personal protective equipment whereas during SARS 2, concerns focused on the need
      for strict training and patient care protocols. HCWs perceived that their
      experiences were ineffectively integrated into risk management protocols.
      CONCLUSIONS: Protection guidelines failed to completely prevent the transmission
      of SARS to HCWs. Nine percent of the interviewed HCWs who intubated patients
      contracted SARS. A Risk Analysis Framework is presented to facilitate the rapid
      integration of HCWs' experiences into practice guidelines.

PMID- 16434752
TI  - Pulse oximeters demonstrate different responses during hypothermia and changes in
      perfusion.
AB  - PURPOSE: Several new pulse oximeters using updated algorithms are marketed as
      being resistant to motion and hypoperfusion. The purpose of this study was to
      compare the performance of three pulse oximeters under conditions of hypothermia
      and altered perfusion. METHODS: Ten male volunteers were enrolled in this study
      after Institutional approval and obtaining informed consent. The probe of the
      Dolphin 2100, Nellcor N-595, or Masimo SET radical version 4.2 was attached to
      the left index finger. Time from 'power on' to acquire the pulse wave and oxygen
      saturation (SpO2), time from the application of air tourniquet with 250 mmHg on
      the upper arm to loss of pulse wave and SpO2, and time from the release of the
      tourniquet to acquire the pulse wave and SpO2 were measured. Then, the patient's
      left hand and arm were cooled gradually to 27 degrees C dermal temperature in a
      room at 19 degrees C. The temperatures at loss of the pulse wave and SpO2 were
      recorded. RESULTS: The Nellcor N-595 was the slowest to detect SpO2 and pulse
      wave at 'power on'. The Masimo SET showed pulse wave and SpO2 longer than the
      other two monitors after 'tourniquet on'. The Nellcor N-595 was the fastest to
      show pulse wave and SpO2 following tourniquet release. CONCLUSION: The Masimo SET
      was the slowest to respond to the changes in perfusion, and the Nellcor N-595
      responded the fastest. However, the Nellcor N-595 was the slowest to show SpO2
      and pulse wave at 'power on'.

PMID- 16434753
TI  - Similar incidence of hypotension with combined spinal-epidural or epidural alone
      for knee arthroplasty.
AB  - BACKGROUND: We hypothesized that the incidence of hypotension during total knee
      replacement (TKR) surgery is lower in patients given combined spinal-epidural
      (CSE) anesthesia vs those receiving epidural anesthesia alone. METHODS: In a
      prospective study, 80 American Society of Anesthesiologists I-II patients (aged
      40-80 yr), undergoing elective TKR surgery were randomly assigned to either CSE
      anesthesia (CSE, n = 40) or epidural anesthesia alone (Epidural, n = 40).
      Hemodynamic measurements included oscillometric mean arterial blood pressure
      (MAP), heart rate (HR), and cardiac index (CI) as determined by thoracic
      bioimpedance; systemic vascular resistance (SVR) was calculated. Our primary
      endpoint (outcome) was the number of hypotension episodes (defined as MAP < 70
      mmHg). RESULTS: Using univariate analysis, we found no differences between the
      groups in regards to MAP, HR, CI, or SVR during the perioperative period. The
      incidence of hypotension was similar in both groups (two patients in each group),
      as was the incidence of bradycardia (12 patients in CSE, 7 in Epidural; P = 0.2).
      There were no differences between groups in other hemodynamic measurements
      including CI and calculated SVR. Analgesia supplementation with fentanyl was more
      frequently required in the Epidural group (20 vs 6 patients - P = 0.03).
      CONCLUSION: Combined spinal-epidural anesthesia and epidural anesthesia alone
      during TKR surgery are associated with the same incidence of hypotension with
      statistically and clinically similar hemodynamic responses.

PMID- 16434754
TI  - Lack of a pre-emptive effect of low-dose ketamine on postoperative pain following
      oral surgery.
AB  - PURPOSE: The aim of this study was to assess the effect of pre- vs postincisional
      low-dose iv ketamine on postoperative pain in outpatients scheduled for oral
      surgery under general anesthesia. METHODS: Eighty-four patients were randomly
      assigned to receive intravenously saline before and after surgery in Group 1,
      ketamine 300 microg x kg(-1) iv before and saline after surgery in Group 2,
      saline before and ketamine 300 microg x kg(-1) iv after surgery in Group 3.
      Postoperative analgesia consisted of iv proparacetamol and ketoprofen. Rescue
      analgesia consisted of nalbuphine 200 microg x kg(-1) iv. Analgesia at home
      consisted of oral ketoprofen, and acetaminophen with codeine as rescue analgesia.
      A telephone interview was conducted on the first and second postoperative days.
      RESULTS: There were no significant differences between groups with respect to
      pain scores, the number of patients requiring nalbuphine in the postanesthesia
      care unit (PACU), (36.7%, 38.7%, and 39.5% for Groups 1, 2, and 3 respectively),
      or nalbuphine consumption in the PACU (66.5 microg x kg(-1) +/- 16.8, 75.9 microg
      x kg(-1) +/- 17.5, 66.7 microg x kg(-1) +/- 21.6 for Groups 1, 2, and 3
      respectively). The number of rescue analgesic tablets taken at home, and time to
      first request for rescue analgesia, sedation scores, or side-effects were similar
      amongst groups. No patient required nalbuphine in the ambulatory care unit.
      CONCLUSIONS: There was no benefit to pre-emptive administration of ketamine 300
      microg x kg(-1) iv whether administered pre- or postoperatively.

PMID- 16434756
TI  - Extraluminal use of the Arndt pediatric endobronchial blocker in an infant: a
      case report.
AB  - PURPOSE: Attaining lung isolation in the infant undergoing thoracic anesthesia
      can be challenging for the anesthesiologist. We describe a novel approach to
      performing lung isolation in an infant undergoing thoracotomy for lobectomy using
      an Arndt pediatric endobronchial blocker via an extraluminal technique. CLINICAL
      FEATURES: Lung isolation in an infant was achieved through the use of an Arndt
      pediatric endobronchial blocker placed externally to an endotracheal tube. The
      blocker's placement was facilitated through the use of a pediatric fibreoptic
      brochoscope placed through the guidewire of the extraluminally placed bronchial
      blocker. CONCLUSION: This novel technique may provide an easier and more reliable
      method of attaining single lung ventilation in infants and small children.

PMID- 16434755
TI  - Phosphate salt bowel preparation regimens alter perioperative acid-base and
      electrolyte balance.
AB  - BACKGROUND: Hyperphosphatemic acidosis and severe electrolyte disturbances caused
      by phosphate salts (PO) used for mechanical bowel preparation have been described
      in occasional case reports prior to bowel resection surgery. We hypothesized that
      PO used preoperatively for bowel preparation may cause more pronounced acid base
      and electrolyte changes than polyethylene glycol (PG). METHODS: Forty American
      Society of Anesthesiologists physical status II-III patients were randomly
      allocated to receive either PO or PG for bowel preparation before intra-abdominal
      surgery (bowel resection or other major elective intra-abdominal surgeries).
      Measurements of pH, base deficit, blood gases, lactate, hemoglobin, calcium,
      magnesium, potassium and phosphorus were undertaken before the laxative
      administration, intraoperatively, and postoperatively. RESULTS: Preoperative
      demographic, hemodynamic and laboratory data were similar in the two groups.
      Intraoperative calcium (8.4 [0.6] vs 9 [0.5] mg x dL(-1)) and pH (7.35 [0.04] vs
      7.41 [0.03]) were lower, while lactate (1.3 [0.4] vs 0.9 [0.3] mmol x L(-1)) was
      higher with PO. Postoperative calcium, magnesium and potassium were lower (8
      [0.5] vs 8.9 [0.2] mg x dL(-1), 1.68 [0.3] vs 1.8 [0.4] and 3.5 [0.36] vs 3.7
      [0.33] mEq x L(-1) respectively) while phosphorus (4.1 [0.3] vs 3.3 [0.2] mEq x
      L(-1)) was higher with PO. A higher percentage of abnormal values for calcium,
      potassium, phosphorus and base deficit (66% vs 33%, 25% vs 10%, 19% vs 2% and
      28.3% vs 5% respectively) were observed with PO. CONCLUSIONS: Calcium and
      magnesium changes were more pronounced in patients who received PO for bowel
      preparation.

PMID- 16434757
TI  - Protamine sulfate causes endothelium-independent vasorelaxation via inducible
      nitric oxide synthase pathway.
AB  - PURPOSE: The precise mechanism of systemic hypotension frequently observed with
      the use of protamine is unclear. Although it has been reported that protamine
      stimulates the release of nitric oxide (NO) from endothelium NO synthase (eNOS),
      the association with inducible NOS (iNOS) remains unknown, despite the induction
      of iNOS by lipopolysaccharides (LPS) and/or inflammatory cytokines during
      cardiopulmonary bypass (CPB). The purpose of this study was to determine whether
      protamine stimulates the release of NO from iNOS induced by LPS. METHODS: We
      performed prospective and controlled functional examinations with isolated
      endothelium-denuded thoracic aortas from 21 male Wister rats. Aortic strips were
      mounted in Krebs solution and treated with LPS (1 microg x mL(-1)) for six hours
      to induce iNOS. Changes in tension caused by L-arginine (a substrate of NOS),
      protamine or a heparin-protamine complex (heparin: protamine = 1 unit: 10 microg)
      were measured in strips pre-contracted by phenylephrine. RESULTS: No drug relaxed
      the strips before LPS-treatment, but each drug relaxed the strips in a dose
      dependent manner after LPS-treatment (P < 0.05). Aminoguanidine (an iNOS
      inhibitor) and methylene blue (a guanylyl cyclase inhibitor) inhibited the
      relaxations. CONCLUSION: These results indicate that protamine and the heparin
      protamine complex stimulated the release of NO from iNOS. As iNOS is induced
      during CPB, protamine or a heparin-protamine complex might cause systemic
      hypotension, at least in part, by stimulating iNOS.

PMID- 16434758
TI  - Acute diastolic dysfunction in thoracoabdominal aortic aneurysm surgery.
AB  - PURPOSE: To report transesophageal echocardiographic (TEE) findings consistent
      with intraoperative acute diastolic dysfunction in a series of patients
      undergoing thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: A series of
      nine consecutive patients underwent TAAA repair with intraoperative TEE
      monitoring. Surgical repair was performed with the adjunct of a left atrio
      femoral bypass. Invasive arterial and venous pressures were monitored.
      Intraoperative TEE was utilized to assess the diastolic function before, and
      during aortic cross clamping. Diastolic dysfunction was defined as a mitral
      inflow pulsed wave Doppler (E: A ratio) < 1. RESULTS: All patients demonstrated
      an E: A ratio > 1 (1.3 +/- 0.08) before aortic cross clamping. During cross
      clamp, the E: A ratio decreased to < 1 (0.75 +/- 0.05) in six of nine patients
      consistent with diastolic dysfunction. The three patients who did not develop E:
      A changes were receiving ss-blockers pre-operatively. Patients with diastolic
      dysfunction were treated with nitroglycerin infusions, which resulted in
      restoration of their E: A ratios > 1 (1.2 +/- 0.09). Three of the patients with
      intraoperative diastolic dysfunction developed postoperative myocardial
      infarction. CONCLUSIONS: Chronic diastolic dysfunction is a well-known entity.
      This report describes acute diastolic dysfunction, which was observed frequently
      in patients undergoing TAAA during aortic cross clamp. Further research is
      required to confirm this phenomenon and determine its possible association with
      increased postoperative cardiac morbidity.

PMID- 16434759
TI  - Role of Erk1/2, p70s6K, and eNOS in isoflurane-induced cardioprotection during
      early reperfusion in vivo.
AB  - PURPOSE: Administration of isoflurane during early reperfusion after prolonged
      coronary artery occlusion decreases myocardial infarct size by activating
      phosphatidylinositol-3-kinase (PI3K) signal transduction. The extracellular
      signal-related kinases (Erk1/2) represent a redundant mechanism by which
      signaling elements downstream from PI3K, including 70-kDA ribosomal protein s6
      kinase (p70s6K) and endothelial nitric oxide synthase (eNOS), may be activated to
      reduce reperfusion injury. We tested the hypothesis Erk1/2, p70s6K, and eNOS
      mediate isoflurane-induced postconditioning in rabbit myocardium in vivo.
      METHODS: Barbiturate-anesthetized rabbits (n = 78) instrumented for measurement
      of systemic hemodynamics were subjected to a 30-min coronary occlusion followed
      by three hours reperfusion. Rabbits were randomly assigned to receive 0.9% saline
      (control), the Erk1/2 inhibitor PD 098059 (2 mg x kg(-1)), the p70s6K inhibitor
      rapamycin (0.25 mg x kg(-1)), the nonselective nitric oxide synthase (NOS)
      inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 mg x kg(-1)), the selective
      inducible NOS antagonist aminoguanidine hydrochloride (AG, 300 mg x kg(-1)), or
      the selective neuronal NOS inhibitor 7-nitroindazole (7-NI, 50 mg x kg(-1)) in
      the presence or absence of 1.0 minimum alveolar concentration isoflurane
      administered for three minutes before and two minutes after reperfusion. RESULTS:
      Brief exposure to 1.0 minimum alveolar concentration isoflurane reduced (P <
      0.05) infarct size (21 +/- 4% [mean +/- SD] of left ventricle area at risk,
      respectively; triphenyltetrazolium staining) as compared to control (41 +/- 5%).
      PD 098059, rapamycin, and L-NAME, but not AG nor 7-NI, abolished the protection
      produced by isoflurane. CONCLUSION: The results suggest that the protective
      effects of isoflurane against infarction during early reperfusion are mediated by
      Erk1/2, p70s6K, and eNOS in vivo.

PMID- 16434760
TI  - Upper airway compromise secondary to edema in Graves' disease.
AB  - PURPOSE: We report an unusual case of upper airway compromise in a patient with
      Graves' disease. We speculate that this complication may be due, in part, to
      poorly controlled hyperthyroidism. CLINICAL FEATURES: A 26-yr-old female
      suffering from Graves' disease underwent a total thyroidectomy. Awake fibreoptic
      intubation was attempted because of a large goiter and orthopnea. Upper airway
      edema impeded the passage of an armored 7.5 mm endotracheal tube. She was
      subsequently intubated awake with a regular 7.5 mm endotracheal tube under direct
      laryngoscopy over an Eschmann bougie. The patient was extubated in the operating
      room over a tube exchanger. Two hours later she developed stridor and upper
      airway obstruction. Using direct laryngoscopy, she was reintubated with
      difficulty because of upper airway edema. At this time, she manifested signs of
      thyrotoxicosis which were managed medically. On postoperative day three she
      underwent a tracheostomy after failing a trial of extubation. The upper airway
      was edematous with minimal vocal cord movement. On postoperative day nine the
      tracheostomy was downsized and the patient was sent home. The vocal cords were
      still edematous with minimal movement. Three weeks later, she demonstrated normal
      right vocal cord movement and weak left vocal cord movement, and the tracheostomy
      was decannulated. CONCLUSIONS: Uncontrolled hyperthyroid patients with large
      goiters secondary to Graves' disease may develop edema of the upper airway. A
      high degree of vigilance for airway obstruction is necessary, with a carefully
      planned approach at each stage of the patient's hospital course to treat this
      potentially life-threatening situation.

PMID- 16434761
TI  - Advantages of ProSeal and SLIPA airways over tracheal tubes for gynecological
      laparoscopies.
AB  - PURPOSE: To compare the efficacy of the ProSeal LMA and SLIPA supralaryngeal
      airways (SLA) with the standard tracheal tube (TT) in 150 consecutive day-case
      laparoscopic gynecological surgery procedures requiring general anesthesia.
      METHODS: One hundred and fifty patients were randomized into three groups. An
      identical general anesthesia technique was used in all patients apart from the
      addition of muscle relaxants and reversal drugs in the TT group. Patients were
      excluded if there were risk factors for gastroesophageal reflux. Ease of use,
      quality of seal, ventilation, systolic pressure, response to intubation, side
      effects and operating room time were assessed. RESULTS: Both ProSeal LMA and
      SLIPA were easy to insert (100% success) and ventilate with respective mean
      (standard deviation) maximum sealing pressures of 31 (4.6) and 30 (5.2) cmH2O (P
      = 0.4) with no muscle relaxants. The seal quality in both ProSeal LMA and SLIPA
      permitted the use of low flows, 485 (291) and 539 (344) mL x min(-1) (P = 0.2)
      respectively, although in the TT group significantly lower flows [377 (124) mL x
      min(-1)], (P < 0.01) were achieved. Systolic pressure in the SLA groups was more
      stable in response to insertion than in the TT. With ProSeal there was a lower
      incidence of sore throats than with TT (30% vs 57%), (P < 0.05), but there was a
      lesser difference as compared with SLIPA (30% vs 49%), (P > 0.05). With both
      SLAs, there was a significant reduction in operating room time (> three minutes),
      (P < 0.001). CONCLUSIONS: These results suggest that the ProSeal LMA (reusable)
      and SLIPA (single-use) SLAs were easy to use without requiring muscle relaxants,
      and reduce operating room time compared to the TT technique in day case
      laparoscopies.

PMID- 16434762
TI  - Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine
      A1 receptor antagonists.
AB  - PURPOSE: To investigate the role of the adenosine A1 receptor in the rapid
      tolerance to cerebral ischemia induced by isoflurane preconditioning. METHODS:
      Seventy-five rats were randomly assigned into five groups (n = 15 each): Control,
      8-cyclopentyl-1,3-dipropulxanthine (DPCPX), Isoflurane, DPCPX+Isoflurane and
      Vehicle+Isoflurane groups. All animals underwent right middle cerebral artery
      occlusion (MCAO) for two hours. Isoflurane preconditioning was conducted one hour
      before MCAO in Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups by
      exposing the animals to 1.5% isoflurane in 98% oxygen for one hour. In the
      Control and DPCPX groups, animals were exposed to 98% oxygen one hour before MCAO
      for one hour. A selective adenosine A1 receptor antagonist, DPCPX, was
      administered (0.1 mg x kg(-1)) 15 min before isoflurane/oxygen exposure in the
      DPCPX and DPCPX+Isoflurane groups to evaluate the effect of adenosine A1 receptor
      antagonist on isoflurane preconditioning. Dimethyl sulfoxide, the solvent of
      DPCPX, was administered (1 mL x kg(-1)) 15 min before isoflurane exposure in the
      Vehicle+Isoflurane group. Neurological deficit scores and brain infarct volumes
      were evaluated 24 hr after reperfusion. RESULTS: Animals in the Isoflurane and
      Vehicle+Isoflurane groups developed lower neurological deficit scores and smaller
      brain infarct volumes than the Control group (P < 0.01). Animals in the
      DPCPX+Isoflurane group developed higher neurological deficit scores and larger
      brain infarct volumes than the Isoflurane and Vehicle+Isoflurane groups (P <
      0.01). CONCLUSION: The present study demonstrates that preconditioning with
      isoflurane reduces focal cerebral ischemic injury in rats, and the adenosine A1
      receptor antagonist (DPCPX) attenuates the neuroprotection induced by isoflurane
      preconditioning.

PMID- 16434764
TI  - Temperature, the benzoylcholine substrate, and fluoride inhibition of
      pseudocholinesterase.

PMID- 16434763
TI  - Postoperative coma in a patient with complete basilar syndrome after anterior
      cervical discectomy.
AB  - PURPOSE: Ischemic brainstem stroke resulting from occlusion of the basilar artery
      during cervical spine surgery in a previously asymptomatic patient is a rare
      event. We report the development of a large ischemic brainstem stroke, resulting
      from occlusion of the basilar artery during anterior cervical discectomy, in a
      patient without previous neurological deficit, or signs of vertebrobasilar
      insufficiency. CLINICAL FEATURES: A 55-yr-old, diabetic and hypertensive male who
      developed a cervical spine infection, underwent surgery for anterior discectomy
      at C5-C6. During the 2.5-hr long procedure the patient was lying supine with his
      neck hyperextended. Except for a temporary reduction in systolic blood pressure,
      the intraoperative course was uneventful. At the end of surgery the patient
      remained unconscious with flaccid paralysis in all extremities, fixed pinpoint
      pupils, low respiratory rate, and no response to painful stimuli. Naloxone
      administration did not improve the clinical picture, while brain computed
      tomography showed a large brainstem and cerebellar stroke, implicating basilar
      artery occlusion. The patient died five days later from stroke complications.
      Intraoperative surgical manipulation with a severely inflamed vertebral system,
      as well as prolonged neck hyperextension occluding the blood flow of
      vertebrobasilar arteries might have contributed to fatal brainstem stroke in this
      patient. CONCLUSION: Neck surgery carries a potential risk for posterior
      circulation stroke, and this report heightens awareness of this rare, but serious
      complication.

PMID- 16434765
TI  - Landiolol and peri-induction tachycardia.

PMID- 16434766
TI  - A long endotracheal tube to facilitate intubation via the Fastrach laryngeal mask
      airway.

PMID- 16434767
TI  - Air humidification might help to prevent irritation and damage to the vocal cords
      during intermittent positive pressure ventilation using a laryngeal mask airway.

PMID- 16434768
TI  - Transient postoperative aphonia following instillation of bupivacaine into the
      shoulder joint.

PMID- 16434769
TI  - Intubation with the GlideScope videolaryngoscope using the "gear stick
      technique".

PMID- 16434770
TI  - Public Health Service evolves to meet nation's needs: pharmacists play pivotal
      roles in PHS history.

PMID- 16434771
TI  - Nation still unprepared for health crisis.

PMID- 16434772
TI  - Michigan hospital captures national quality award.

PMID- 16434773
TI  - Study examines adverse-drug-event costs for antimicrobials.

PMID- 16434775
TI  - Collaborative practice agreement for diabetes management.

PMID- 16434776
TI  - Fostering leadership and professionalism.

PMID- 16434777
TI  - Attainment of cholesterol guidelines in patients at high risk for coronary heart
      disease.

PMID- 16434778
TI  - Proton-pump inhibitors for upper-gastrointestinal bleeding.

PMID- 16434779
TI  - Proton-pump inhibitors for upper-gastrointestinal bleeding.

PMID- 16434780
TI  - Improving the accuracy of patient identification in the medication-use process.

PMID- 16434781
TI  - Unlabeled uses of botulinum toxins: a review, part 2.
AB  - PURPOSE: Efficacy and safety data regarding the unlabeled uses of botulinum
      toxins are reviewed, and the pharmacology, adverse effects, and characteristics
      of commercially available botulinum toxins are discussed. SUMMARY: More than 300
      articles have been published on the use of botulinum toxins, particularly
      botulinum toxin type A, to treat conditions characterized by excessive smooth or
      skeletal muscle spasticity. Botulinum toxins are synthesized by Clostridium
      botulinum and cause temporary local paralysis of the injected muscle by
      inhibiting acetylcholine release at the neuromuscular junction. While botulinum
      toxins have Food and Drug Administration-approved labeling to treat a limited
      number of spasticity disorders, including cervical dystonia and blepharospasm,
      the toxins have more than 50 reported therapeutic uses. Among these uses, the
      most rigorously studied indications include achalasia, essential tremors, palmar
      hyperhidrosis, chronic anal fissures, headache prophylaxis, and limb spasticity.
      The main adverse effects of the toxins are pain and erythema at the injection
      site, although unintended paralysis of muscles adjacent to the site of toxin
      injection may also occur. CONCLUSION: Clinical studies support the use of
      botulinum toxins for certain conditions, although more studies are needed to
      establish the role of the drug relative to conventional therapies and to
      determine patient predictors of response. Although botulinum toxins are generally
      well tolerated, a patient-specific risk-benefit assessment should precede any
      decision to use them for unlabeled indications.

PMID- 16434782
TI  - Recognizing and treating depression in children and adolescents.
AB  - PURPOSE: The clinical presentation and neurobiology of depression in youth and
      its appropriate treatment, as well as strategies for improving therapeutic
      benefit and preventing adverse outcomes, including suicide, are reviewed.
      SUMMARY: Functionally impairing depression occurs in 2-10% of children and
      adolescents. A diagnosis of depression should be considered when a physically
      healthy child exhibits depressed mood or anhedonia, multiple somatic complaints,
      or behavioral changes, such as bullying, aggression, and social withdrawal. Risk
      factors for depression include childhood trauma, genetic susceptibility, and
      environmental stressors. Antidepressants and cognitive behavioral therapy are the
      most effective treatments for adolescents with depression. Youth are at risk for
      the same adverse effects as adults but have an increased risk of behavioral
      activation, or switch, to mania and suicidal thoughts and behaviors early in
      treatment. Compared with other antidepressants, fluoxetine has the most evidence
      for safety and efficacy, particularly in adolescents 12 years or older. There is
      very little evidence for the effectiveness of any antidepressant in children 11
      years and younger. Youth receiving antidepressants should be monitored closely
      for new-onset or worsening suicidality, particularly during the first two weeks
      after starting medication, and for three months of therapy. Behavioral
      activation, aggression, worsening depression, anxiety, insomnia, or impulsivity
      can herald a switch to mania or suicidality. CONCLUSION: Depression in youth is
      common and treatable and responds best to multimodal treatment combining patient
      and family education, cognitive behavioral therapy, and antidepressant
      medication. The potential benefits of antidepressants outweigh the risks for
      adolescents. Family and psychotherapeutic interventions are most effective for
      prepubertal children.

PMID- 16434783
TI  - Supplementary prescribing by pharmacists in England.
AB  - PURPOSE: The implementation of supplementary prescribing by pharmacists within
      primary care trusts (PCTs) and secondary care trusts (SCTs) in England was
      studied. METHODS: A survey was developed and sent to pharmacists in PCTs and SCTs
      in England who would oversee the implementation of supplementary prescribing by
      pharmacists. RESULTS: The response rate was 68% for both surveys. The majority of
      SCTs and PCTs intended to implement supplementary prescribing by pharmacists by
      the end of 2005 (57% and 56%, respectively). The majority of SCT respondents did
      not believe that it would be more difficult to recruit designated medical
      practitioners to supervise supplementary prescribing training for pharmacists as
      opposed to nurses (67%, n = 43), whereas the largest group of PCT pharmacists
      believed it would be (47%, n = 86). Within secondary care, the clinical areas in
      which pharmacists were intending to work as supplementary prescribers were those
      where they already had established roles. Within primary care, the main clinical
      areas for pharmacists were influenced by those areas in the new General Medical
      Services contract Quality and Outcomes Framework for general practitioners.
      CONCLUSION: A survey investigating the implementation of supplementary
      prescribing by pharmacists in England found that there were significantly more
      barriers to its establishment within primary care than secondary care settings.
      Within primary care, supplementary prescribing is being implemented to develop
      new services. Within secondary care, the supplementary prescribing model is more
      often used to legitimize services already being provided.

PMID- 16434784
TI  - Extemporaneous sildenafil citrate oral suspensions for the treatment of pulmonary
      hypertension in children.
AB  - PURPOSE: The stability of sildenafil citrate 2.5 mg/mL in two extemporaneously
      prepared oral suspensions stored at 4 and 25 degrees C was studied. METHODS:
      Thirty 25-mg tablets of sildenafil citrate were ground to powder, and the powder
      was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of
      methylcellulose 1% and Simple Syrup, NF, to produce two 2.5-mg/mL suspensions.
      Five plastic bottles of each suspension were stored in amber plastic prescription
      bottles at 4 or 25 degrees C. Samples were collected on days 0, 7, 14, 28, 42,
      56, 70, and 91 for analysis of sildenafil content by high-performance liquid
      chromatography; pH was also measured. Samples were visually observed against
      black and white backgrounds. RESULTS: The mean concentration of sildenafil
      citrate exceeded 98% of the initial concentration in all samples at both
      temperatures throughout the 91-day study period. No changes in pH, odor, or
      physical appearance were observed. CONCLUSION: Sildenafil citrate 2.5 mg/mL in
      two extemporaneously compounded oral suspensions was stable for 91 days in
      plastic prescription bottles at 4 and 25 degrees C.

PMID- 16434785
TI  - Personal digital assistants for documenting primary care clinical pharmacy
      services in a health maintenance organization.

PMID- 16434786
TI  - Acute hypermagnesemia in a child.

PMID- 16434787
TI  - Cluster approach to the Ti2Ni structure type.
AB  - It has been established that the 16(c) first coordination clusters in the Ti2Ni
      structure type (space group Fd3m) follow icosahedral-face orientational ordering
      along regular tetrahedron edge directions. The actual crystal structure appears
      due to the prevalence of the face-centred cubic translational ordering over the
      cluster assembling. This way, the competition of the ;regular' crystal phase and
      its icosahedral analogue is reconstructed at the atomic level. The model accounts
      for the markedly different electronic characteristics at the different
      crystallographic positions obtained by hyperfine interaction measurements, and
      other curious experimental facts help to create an exact physical definition of
      the first coordination in the solid state and to distinguish between various
      structure types on fundamental principles.

PMID- 16434788
TI  - Review of polyhedral distortions as a multi-scale minimization of the electric
      polarization and their correlations with physical properties.
AB  - The Jahn-Teller (JT) and non-Jahn-Teller polyhedral distortions are reviewed
      within the same context, based on a multi-scale minimization of the electric
      polarization by handling formal ionic valences and valence electron density. This
      model is applied to tetragonal distortions of octahedra, particularly in K2NiF4
      structures with different formula types, along with doping. The predictions are
      always in good agreement with the observed data. In particular, the
      ferrodistortive order of JT distortions is obtained from formal charge
      polarizations, while the antiferrodistortive one is adopted when only the valence
      electron density is involved. The correlations between physical properties and
      octahedral elongations through the crystal structures on one side and chemical
      compositions on the other side are discussed according to this model for high-Tc
      cuprate superconductors and CMR manganites.

PMID- 16434789
TI  - Structure model for the tau(mu) phase in Al-Cr-Si alloys deduced from the lambda
      phase by the strong-reflections approach.
AB  - There are very obvious common features in the electron diffraction patterns of
      the lambda and tau(mu) phases in the Al-Cr-Si system. The positions of the strong
      reflections and their intensity distributions are similar for the two structures.
      The relation of the reciprocal lattices of the lambda and tau(mu) phases is
      studied. By applying the strong-reflections approach, the structure factors of
      tau(mu) are deduced from the corresponding structure factors of the known lambda
      phase. Rules for selecting reflections for the strong-reflections approach are
      described. Similar to that of lambda, the structure of tau(mu) contains six
      layers stacked along the c axis in each unit cell. There are 752 atoms in each
      unit cell, 53 of them are unique. The corresponding composition of the tau(mu)
      model is Al(3.82 - x)CrSi(x). Simulated electron diffraction patterns from the
      structure model are in good agreement with the experimental ones. The arrangement
      of interpenetrated icosahedral clusters in the tau(mu) phase is discussed.

PMID- 16434790
TI  - Systematic prediction of new ferroelectrics in space group R3. I.
AB  - Release 2005/1 of the Inorganic Crystal Structure Database contains 158 entries
      under the space group R3. The first 81 together with 15 related entries include
      52 different structure types, 10 of which represent families that have two or
      more isostructural members. There are 18 types that satisfy the structural
      criteria for ferroelectricity with a confidence level that necessarily depends
      upon the reliability of each structural determination. Among them,
      (LiTaO3)9.Ta2O5 and the CsCd(NO2) family are known ferroelectrics. The remaining
      16 include the high-intensity higher-order harmonic generator II-BaB2O4, not
      previously recognized as ferroelectric. The other predicted ferroelectrics are
      Te(OH)6.NaF, the MgSO3.6H2O family, Li3P3O9.3H2O, SeNbF9, Al2(H2PO4)3PO4.6H2O,
      [Cr(OCN2H4)6].[(Co(NH3)2(NO2)4]3.(H2O)(1.5)], NaZnBr3.5H2O, III-Ag3SI, Tl2S, the
      Ba3Yb4O9 family, the Fe(10.7)Ru(1.3)As5 family, Sr17Ta10S42, Pb8Sb3 and the
      Sc7I12C family. Six structures reported in the space group R3 most likely exhibit
      mirror symmetry, with three experimental confirmations. The other 19 structures
      are most likely nonpolar, with six experimental confirmations. The capacity for
      physical property prediction by the remaining ten structures is shown to be in
      doubt. Thus, 46% of the present 52 inorganic structure types initially determined
      in the space group R3 and 35% of those currently assigned to R3 more likely
      exhibit an additional inversion center, mirror or glide plane, strongly exceeding
      the recently reported error rate of approximately 11% in organic structures.

PMID- 16434791
TI  - Structural disorder of a new zeolite-like lithosilicate,
      K(2.6)Li(5.4)[Li4Si16O38].4.3H2O.
AB  - The framework structure of the synthetic microporous lithosilicate RUB-30
      (K(2.6)Li(5.4)[Li4Si16O38].4.3H2O) is similar to that of the fibrous zeolites
      such as natrolite, edingtonite and thomsonite, since all their frameworks include
      the same secondary structural building unit, the so-called 4-1 T5O10 cluster of
      tetrahedra. Unique to the structure of RUB-30, each 4-1 unit consists of a
      LiSi4O10 moiety within which the single [LiO4] tetrahedron is strictly segregated
      from the other four [SiO4] tetrahedra. The connection of neighboring 4-1 units
      through edge-sharing [LiO4] tetrahedra results in a new framework topology. The
      present work reports an ;average' structure of RUB-30 solved by synchrotron X-ray
      single-crystal diffraction data collected at a second-generation source. A
      superstructure with a x 2b x c (relative to the subcell quoted above) could be
      seen in X-ray diffraction data collected with better resolution and higher
      brightness at a third generation source. Diffuse streaks along k with l = odd and
      unusual superstructure hkl reflections, with k = odd and l = odd only, indicate a
      more complicated real structure of the material. To explain this observation we
      propose two different structure types which are statistically, but coherently,
      intergrown in RUB-30.

PMID- 16434792
TI  - Getting more out of an incommensurately modulated structure: the example of
      K5Yb(MoO4)4.
AB  - A method based on the superspace approach is presented with the aim of generating
      a family of modular structures from a single incommensurately modulated
      structure. This approach based on the variation of the modulation vector q is
      applied to the generation of the K5Yb(MoO4)4, potassium ytterbium tetramolybdate,
      family of modular structures. The beta coefficient of the modulation vector q =
      betab* is a temperature-dependent variable which determines the modification. Our
      method gives a unified frame to describe and explain the three temperature
      dependent phases of K5Yb(MoO4)4. Phase beta can be represented as a polytypic
      modification with 1/2b* < or = q < or = 2/3b*; phases gamma (q = 1/2b*) and alpha
      (q = 1b*) are the lowest and the highest temperature members of the K5Yb(MoO4)4
      family, respectively.

PMID- 16434793
TI  - Structures of the cation-deficient perovskite Nd(0.7)Ti(0.9)Al(0.1)O3 from high
      resolution neutron powder diffraction in combination with group-theoretical
      analysis.
AB  - The crystal structures of Nd(0.7)Ti(0.9)Al(0.1)O3, taken to represent the ideal
      Nd(2/3)TiO3, have been elucidated from 4 to 1273 K using high-resolution neutron
      powder diffraction in combination with group-theoretical analysis. The room
      temperature structure is monoclinic in C2/m, on a cell with a = 7.6764 (1), b =
      7.6430 (1), c = 7.7114 (1) A, beta = 90.042 (2) degrees . Pertinent features are
      the layered ordering of the A-site Nd cations/vacancies along the z axis and out
      of-phase tilting of the (Ti/Al)O6 octahedra around both the x and z axes. From
      about 750 to 1273 K, the octahedra are tilted around just one axis (x axis)
      perpendicular to the direction of the cation ordering, giving rise to an
      orthorhombic structure with space-group symmetry Cmmm.

PMID- 16434794
TI  - Temperature-resolved study of three [M(M'O4)4(TBPO)4] complexes (MM' = URe, ThRe,
      ThTc).
AB  - The crystal structures of the title complexes were measured at several
      temperatures between room temperature and 100 K. Each sample shows reversible
      crystal-to-crystal phase transitions as the temperature is varied. The behaviour
      of [U(ReO4)4(TBPO)4] (I) and [Th(ReO4)4(TBPO)4] (II) (TBPO = tri-n-butylphosphine
      oxide) is very similar; at room temperature, crystals of (I) and (II) are
      isostructural, with space group I42m, and reducing the temperature to 100 K
      causes a lowering of the space-group symmetry to C-centred cells, space groups Cc
      for (I) and Cmc2(1) for (II). The variation of lattice symmetry of
      [Th(TcO4)4(TBPO)4] (III) was found to be somewhat different, with the body
      centred cubic space group, I43m, occurring at 293 K, a reduction of symmetry at
      230 K to the C-centred orthorhombic space group, Cmc2(1), and a further
      transition to the primitive orthorhombic space group, Pbc2(1), below 215 K.
      Elucidation of the correct space-group symmetry and the subsequent refinement was
      complicated in some cases by the twinning by pseudo-merohedry that arises from
      the lowering of the space-group symmetry, occurring as the temperature is
      reduced. All three of the crystal structures determined at room temperature have
      high atomic displacement parameters, particularly of the (n)Bu groups, and (III)
      shows disorder of some of the O atoms. The structures in the space group Cmc2(1),
      show some disorder of nBu groups, but are otherwise reasonably well ordered; the
      structures of (I) in Cc and (III) in Pbc2(1) are ordered, even to the ends of the
      alkyl chains. Inter-comparison of the structures measured below 293 K, using the
      program OFIT from the SHELXTL package, showed that generally, they are remarkably
      alike, with weighted r.m.s. deviations of the M, M' and P atoms of less than 0.1
      A, as are the 293 K structures of (I) and (II) with their low-temperature
      counterparts. However, the structure of (III) measured in the space group Cmc2(1)
      is significantly different from both the structure of (III) at 293 K and that
      found below 215 K, with weighted r.m.s. deviations of the Th, Tc and P atoms of
      0.40 and 0.37 A, respectively. An extensive network of weak intra- and
      intermolecular C-H...O hydrogen bonds found between the atoms of the nBu and
      [M'O4] groups probably influences the packing and the overall geometry of the
      molecules.

PMID- 16434795
TI  - Absence of halogen...halogen interactions in chlorotrimethylsilane polymorphs.
AB  - The structures of in situ pressure-frozen chlorotrimethylsilane crystals,
      (CH3)3SiCl, have been determined at 0.23, 0.30 and 0.58 GPa. The molecular
      arrangements in the low-temperature and high-pressure phases are two
      dimensionally isostructural, but different in the third perpendicular direction.
      Consequently, a striking similarity exists between the unit-cell dimensions of
      these polymorphs. The absence of short Cl...Cl contacts, both in the low
      temperature or pressure-frozen phases of (CH3)3SiCl, has been rationalized in
      terms of the favoured packing patterns and comparable energies of
      halogen...halogen interactions and other van der Waals forces.

PMID- 16434796
TI  - Pressure-frozen benzene I revisited.
AB  - The crystal structure of benzene, C6H6, in situ pressure-frozen in phase I, has
      been determined by X-ray diffraction at 0.30, 0.70 and 1.10 GPa, and 296 K. The
      molecular aggregation within phase I is consistent with van der Waals contacts
      and electrostatic attraction of the positive net atomic charges at the H atoms
      with the negative net charges of the C atoms. The C-H...aromatic ring centre
      contacts are the most prominent feature of the two experimentally determined
      benzene crystal structures in phases I and III, whereas no stacking of the
      molecules has been observed. This specific crystal packing is a likely reason for
      the exceptionally high polymerization pressure of benzene. The changes of
      molecular arrangement within phase I on elevating the pressure and lowering the
      temperature are analogous.

PMID- 16434797
TI  - Structure of N6-furfurylaminopurine (kinetin) dihydrogenphosphate.
AB  - The crystal structure of kinetin dihydrogenphosphate has been determined at 115
      and 293 K. Kinetin dihydrogenphosphate undergoes a polymorphic phase transition
      at 291.1 K. In both phases the crystal belongs to the triclinic system with the
      symmetry described by the space group P?bar 1. In the low-temperature phase, the
      unit cell is doubled along the a axis. There is a dynamic equilibrium between
      different tautomeric forms of the adenine residue, determined by the distribution
      of H atoms within the network of hydrogen bonds.

PMID- 16434798
TI  - 3,5-Dihalo-4-hydroxybenzonitriles: isostructures, polymorphs and solvates.
AB  - 3,5-Dichloro-4-hydroxybenzonitrile and its solvates with benzene and xylene
      assemble in chain-like arrangements held together by OH...NC interactions. Two
      polymorphs each of the corresponding dibromo and diiodo compounds form similar
      chains which are then bound together by X...X interactions to form approximately
      planar sheets. These sheets are essentially identical in all four of the bromo
      and iodo compounds and have approximate p2gg two-dimensional symmetry. These four
      compounds form an extreme example of two-dimensional isostructuality. The
      polymorphs differ in the stacking arrangements. One of the Br polymorphs is
      isostructural with one of the I polymorphs.

PMID- 16434799
TI  - Five varieties of hydrogen bond in 1-formyl-3-thiosemicarbazide: an electron
      density study.
AB  - In an attempt to investigate the putative S-H...N hydrogen bond, we have studied
      the title compound, 1-formyl-3-thiosemicarbazide, which was revealed in a CSD
      search as a crystal structure which might show such an interaction. However, a
      redetermination of the structure at room temperature and careful analysis showed
      that the earlier study [Saxena et al. (1991). Acta Cryst. C47, 2374-2376] on
      which the CSD search was based was in error and that the possibility of an S
      H...N hydrogen bond is negated. The presence of five other varieties of hydrogen
      bond (N-H...O, N-H...S, N-H...N, C-H...O, C-H...S) in the crystal packing
      prompted us to redirect our efforts and to undertake a study of the charge
      density distribution at 90 K. The topological analysis of these five varieties of
      hydrogen bond was carried out with Bader's quantum theory of ;atoms in molecules'
      and by applying Koch-Popelier's criteria. The analysis reveals that the hydrogen
      bond strength is highest for N-H...O and lowest for C-H...S with N-H...S, N-H...N
      and C-H...O forming the middle order.

PMID- 16434801
TI  - Relationship between structure and photoinitiating abilities of selected bromide
      salts of 2-oxo-2,3-dihydro-1H-imidazo[1,2-a]pyridine (IMP): influence of the
      solvent and the substitution in benzaldehyde on the course of its reaction with
      IMP.
AB  - 2-Oxo-2,3-dihydro-1H-imidazo[1,2-a]pyridinium bromide and its C3-substituted
      derivatives have been synthesized and structurally characterized by X-ray
      crystallography and quantum chemical calculations. Their potential as
      photoinitiators for free-radical polymerization has been investigated
      experimentally and compared with theoretical results. It has been established
      that the course of the reaction that introduces the substituted benzylidene group
      to the imidazole ring is different in the protic and dipolar aprotic solvents,
      and also depends on the character of the substituent, as the energy change in the
      reaction favours either R1R2C=CHR3 or R1R2CH-CH(OCH3)R3 formation.

PMID- 16434800
TI  - Monitoring structural transformations in crystals. 8. Monitoring molecules and a
      reaction center during a solid-state Yang photocyclization.
AB  - Structural changes taking place in a crystal during an intramolecular
      photochemical reaction [the Yang photocyclization of the alpha-methylbenzylamine
      salt with 1-(4-carboxybenzoyl)-1-methyladamantane] were monitored step-by-step
      using X-ray structure analysis. This is the first example of such a study carried
      out for an intramolecular photochemical reaction. During the photoreaction, both
      the reactant and product molecules change their orientation, but the reactant
      changes more rapidly after the reaction is about 80% complete. The distance
      between directly reacting atoms in the reactant molecule is almost constant until
      about 80% reaction progress and afterwards decreases. The torsion angle defined
      by the reactant atoms that form the cyclobutane ring also changes in the final
      stages of the photoreaction. These phenomena are explained in terms of the
      influence of many product molecules upon a small number of reacting molecules.
      The adamantane portion shifts more than the remaining part of the anionic
      reactant species during the reaction, which is explained in terms of hydrogen
      bonding. The structural changes are accompanied by changes in the cell constants.
      The results obtained in the present study are compared with analogous results
      published for intermolecular reactions.

PMID- 16434802
TI  - Polymorphs of p-nitrophenol as studied by variable-temperature X-ray diffraction
      and calorimetry: comparison with m-nitrophenol.
AB  - Crystal structures of two polymorphic forms of p-nitrophenol have been determined
      at several temperatures between 120 and 375 K. The thermal expansion tensor has
      been determined for both polymorphs. The rigid-body mean-square amplitudes of
      molecular translations and librations and the amplitudes of the internal torsions
      of the nitro group have been calculated at different temperatures. Differential
      scanning calorimetry was used to find the temperature and enthalpy of the
      polymorphic transformation. The results were compared with those recently
      obtained for m-nitrophenol polymorphs. Some conclusions concerning the
      polymorphism of p- and m-nitrophenols are presented.

PMID- 16434803
TI  - Neutron diffraction analysis of deuterium transfer in chiral beta-thiolactam
      formation in the crystalline state.
AB  - Since N,N-dibenzyl-1-cyclohexenecarbothioamide is photo-isomerized to the
      optically active beta-thiolactam with the retention of the single-crystal form,
      the mechanism of chirality induction was identified by X-ray crystal structure
      analyses during the process of the reaction [Hosoya et al. (2002). Bull. Chem.
      Soc. Jpn, 75, 2147-2151]. In order to clarify the mechanism of hydrogen transfer
      in the reaction, the H atoms of the benzyl groups were replaced with deuterium
      atoms. The crystal structure after photoisomerization was analyzed by neutron
      diffraction. One of four deuterium atoms of the two benzyl groups is transferred
      to the C atom of the cyclohexene ring. The absolute configuration of the -C*HD-
      group (chiral methylene) in the photoproduct beta-thiolactam revealed that the
      deuterium atom occupies the equatorial position. This suggests that the deuterium
      atom is not transferred from the benzyl group of a neighbouring molecule, but
      from one of the benzyl groups within the molecule.

PMID- 16434804
TI  - Structures and the oxygen deficiency of tetragonal and monoclinic zirconium oxide
      nanoparticles.
AB  - The crystal structure of zirconium oxide nanoparticles was refined by the
      Rietveld analysis of synchrotron X-ray powder diffraction data measured at 298 K.
      In the nanoparticles, two phases of tetragonal ZrO(2 - delta) (average particle
      size: 11 +/- 2 nm) and monoclinic ZrO2 (average particle size: 24 +/- 4 nm)
      existed, where the weight fractions were estimated to be 84.9 and 15.1 wt%,
      respectively. The structural refinement suggests that the tetragonal ZrO(2 -
      delta) has an oxygen deficiency [delta = 0.031 (7)] and that the monoclinic ZrO(2
      - delta) has less oxygen deficiency (delta approximately 0), where delta is the
      vacancy concentration. The monoclinic ZrO2 has a larger unit-cell volume. The
      maximum-entropy method analysis indicated covalent bonding between Zr and O
      atoms.

PMID- 16434807
TI  - Predictors of sub-acute stent thrombosis in acute myocardial infarction patients
      following primary coronary stenting with bare metal stent.
AB  - BACKGROUND: The aim of the present study was to identify the relationship between
      sub-acute stent thrombosis (SAT) and acute-phase inflammatory reactants, such as
      high-sensitivity C-reactive protein (hs-CRP) and serum amyloid-A protein (SAA),
      in patients with acute myocardial infarction (AMI) successfully treated with
      primary coronary stenting. METHODS AND RESULTS: The 381 consecutive AMI subjects
      were reperfused by primary coronary stenting within 24 h of onset. SAT was
      confirmed angiographically in 10 patients (2.6%). There were no significant
      differences between the patients with or without SAT in terms of patient
      characteristics, Killip classification on admission, or stent diameter, nor were
      there significant differences between the 2 groups in terms of left ventricular
      function soon after stenting (left ventricular ejection fraction) or end
      diastolic volume index. The plasma levels of both hs-CRP and SAA were
      significantly higher in the SAT patients than in the others (hs-CRP: 6.7+/-6.7
      mg/dl vs 3.3+/-3.8 mg/dl, p=0.007; SAA: 699+/-812 mug/dl vs 208+/-273 mug/dl,
      p<0.0001). Multivariate analysis identified SAA as an independent predictor of
      SAT (risk ratio: 4.9, 95% confidence interval: 1.7-14.9, p<0.05). CONCLUSION: In
      patients with AMI who are treated with primary coronary stenting, inflammation
      may be closely related to SAT, for which SAA is a useful predictor.

PMID- 16434808
TI  - Serum lipoprotein(a) level and clinical coronary stenosis progression in patients
      with myocardial infarction: re-revascularization rate is high in patients with
      high-Lp(a).
AB  - BACKGROUND: High serum lipoprotein(a) (Lp(a)) levels are associated with coronary
      artery disease. METHODS AND RESULTS: The serum Lp(a) levels of 130 patients with
      acute myocardial infarction (AMI) who underwent direct percutaneous coronary
      intervention were investigated. On the basis of Lp(a) level at 1 month after the
      onset of AMI, the patients were classified into 2 groups (high-Lp(a) (> or =30
      mg/dl) and low-Lp(a) (< 30 mg/dl)) for evaluation of the clinical coronary
      stenosis progression (CCSP) rate. CCSP is defined as either target lesion
      revascularization (TLR) or new lesion revascularization (NLR). The CCSP rate was
      significantly higher in the high-Lp(a) group than in the low-Lp(a) group (65.8%
      vs 29.3%, p<0.01). In patients who had coronary stents in the acute phase (n=79),
      the CCSP and NLR rates were significantly higher in the high-Lp(a) group than in
      the low-Lp(a) group (45.0% vs 20.3%, p<0.05; 35.0% vs 6.8%, p<0.01), but there
      was no significant difference in TLR rate between the 2 groups (10.0% vs 13.6%,
      p=0.858). CONCLUSIONS: High serum Lp(a) level is a significant risk factor for
      CCSP, but does not influence restenosis after stenting.

PMID- 16434809
TI  - N-terminal pro-brain natriuretic peptide is a biomarker of congestive heart
      failure and predictive of 30-day untoward clinical outcomes in patients with
      acute myocardial infarction undergoing primary percutaneous coronary
      intervention.
AB  - BACKGROUND: Increased levels of N-terminal pro-brain natiuretic peptide (NT
      proBNP) are now recognized as a new and useful biochemical marker that is
      predictive of clinical outcomes in patients with congestive heart failure (CHF).
      However, an association between an increased circulating level of this biomarker
      and clinical outcomes in patients following acute myocardial infarction (AMI) has
      not been fully delineated. Thus, the purpose of this study was to test whether NT
      proBNP can predict prognosis in patients following ST-segment elevated AMI.
      METHODS AND RESULTS: A prospective cohort study of 242 consecutive patients with
      ST-segment elevated AMI of onset <12 h who underwent primary percutaneous
      coronary intervention (PCI) was conducted. Blood samples for plasma concentration
      of NT-proBNP were collected following vascular puncture. Univariate analysis
      demonstrated that the 30-day composite major adverse clinical outcomes (MACO)
      [advanced Killip score > or =3, functional class > or =3 of CHF and 30-day
      mortality] were strongly associated with elevated NT-proBNP (>243 pg/ml)
      (p<0.0001), unsuccessful reperfusion (final thrombolysis in myocardial infarction
      flow < or =2) (p<0.0001), left ventricular ejection fraction (LVEF) <45%
      (p<0.0001), diabetes mellitus (DM) (p=0.0004) and multivessel disease (p=0.0005).
      Multiple stepwise logistic regression analysis demonstrated that elevation of NT
      proBNP (p=0.0002), LVEF < 45% (p=0.0003), DM (p=0.0007), unsuccessful reperfusion
      (p=0.006), and age (> or =70 years) (p=0.031) are independent predictors of 30
      day MACO. Additionally, elevation of NT-proBNP, together with advanced Killip
      score and unsuccessful reperfusion, are significant independent predictors of
      increased 30-day mortality (all p values <0.005). CONCLUSION: Increased NT-proBNP
      level was the most independent predictor of 30-day MACO in patients with ST
      segment elevated AMI undergoing primary PCI.

PMID- 16434810
TI  - Long-term follow-up of changes in fibrillation waves in patients with persistent
      atrial fibrillation: spectral analysis of surface ECG.
AB  - BACKGROUND: Little is known about the shortening of atrial refractoriness as a
      result of electrical remodeling in atrial fibrillation (AF) in clinical cases,
      especially in terms of long-term follow-up, because of a lack of noninvasive
      testing methods. METHODS AND RESULTS: The present study population comprised 38
      consecutive patients with persistent AF (PAF, >1 month). Before and after the
      follow-up period of 1-14 months, surface ECGs were recorded for analysis. In each
      case, the fibrillation wave was purified by subtracting the QRS-T complex
      template and then power spectral analysis was performed. The mean fibrillation
      cycle length (FCL) and FCL coefficient of variation (FCL-CV) were determined from
      peak power frequency in 20 epochs in each recording. The change in FCL (FCL) was
      calculated by subtracting the baseline FCL from the FCL after the follow-up
      period. To correct for the difference in the follow-up period, DeltaFCL was
      divided by the follow-up period in each case. In 38 cases, mean FCL decreased
      from 160+/-20 ms to 151+/-19 ms (p<0.05), and the FCL-CV also decreased from 15+/
      9% to 12+/-5% (p<0.05). The corrected DeltaFCL was -2.4+/-7.6 (ms/month) and
      there was a significant negative correlation between corrected DeltaFCL and
      baseline FCL (p<0.01). CONCLUSION: Shortening of the FCL during a relatively long
      term follow-up period was observed in patients with PAF.

PMID- 16434811
TI  - Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary
      arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a poor prognostic disease
      with limited treatment options. Rho-kinase is involved in the pathophysiology of
      several diseases underlying smooth muscle hypercontraction, so the purpose of
      this study was to investigate the efficacy of fasudil, a Rho-kinase inhibitor, in
      patients with PAH. METHODS AND RESULTS: Fasudil 30 mg was intravenously injected
      over 30 min in 8 patients (all female, mean +/- SD, 41+/-11 years) with PAH. The
      lowest total pulmonary resistance (TPR) time was within 30-60 min after
      administration. Administration of fasudil decreased TPR from 1,069+/-573 dyne . s
      . cm (-5) to 809+/-416 dyne . s . cm(-5) (p<0.005) and mean pulmonary arterial
      pressure from 41.3+/-12.8 mmHg to 37.9+/-14.6 mmHg (p<0.05). The cardiac index
      was increased from 2.42+/-0.73 L . min(-1) . m(-2) to 2.84+/-0.79 L . min(-1) .
      m(-2) (p<0.02). Systemic vascular resistance and systolic systemic arterial
      pressure (SAP) were decreased (p<0.005, p=0.09, respectively), but the decrease
      in SAP was small (-6.4+/-9.1 mmHg). CONCLUSION: These results suggest that Rho
      kinase is involved in the pathogenesis of human PAH and that fasudil is a novel
      therapeutic agent.

PMID- 16434812
TI  - Mitral valve repair in patients with infective endocarditis.
AB  - BACKGROUND: The goal of the present study was to investigate the feasibility of
      mitral valvle repair in patients with infective endocarditis (IE). METHODS AND
      RESULTS: Twenty-one patients who had undergone mitral valve surgery for IE were
      reviewed. Valve repair was performed in 8 patients with active and in 6 patients
      with healed endocarditis: 6 of these 14 patients were New York Heart Association
      (NYHA) functional class III or IV preoperatively. Valve replacement was performed
      in 5 patients with active endocarditis and in 2 with healed endocarditis: 6 of
      these 7 patients were NYHA functional class III or IV preoperatively. Repair
      techniques included annuloplasty (n=13), resection-suture (n=13), chordal
      transfer (n=2), and closure of the perforation (n=3). In the valve replacement
      group, 6 patients required concomitant aortic valve replacement. In the valve
      repair group, 1 patient died and 1 patient required reoperation for recurrent
      mitral regurgitation. Postoperative echocardiography demonstrated no (n=8) or
      mild (n=4) mitral regurgitation at the last follow-up examination. In the valve
      replacement group, 1 patient died and 1 patient required reoperation because of a
      paravalvular leak. No cases of recurrent infection occurred in either group.
      CONCLUSIONS: Mitral valve repair in patients with IE is feasible and has low
      morbidity.

PMID- 16434813
TI  - Diagnostic significance of positive I-123 BMIPP despite negative stress Tl-201
      myocardial imaging in patients with suspected coronary artery disease.
AB  - BACKGROUND: There is frequently discordance in the interpretation of myocardial
      single-photon emission computed tomography images using both rest iodine-123 15
      (p-iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP) and stress thallium-201
      ((201)Tl); that is, negative BMIPP vs positive (201)Tl studies. However, little
      attention has been paid to reverse discordance (ie, positive BMIPP despite
      negative stress (201)Tl). METHODS AND RESULTS: In the present study 105
      consecutive patients with suspected coronary artery disease (CAD) who underwent
      both rest BMIPP and stress (201)Tl imaging were evaluated. No patient with
      previous myocardial infarction was included. Scintigraphic studies revealed that
      BMIPP was in concordance with (201)Tl in 71 patients: both were positive in 38
      and negative in 33, whereas both were discordant in 20 and reverse discordant in
      14. In patients with reverse discordance, the pattern of BMIPP abnormality was
      segmental in 8 and spotty in 6; the former was related to coronary territory.
      Based on the BMIPP findings and clinical symptoms, 7 patients with positive BMIPP
      despite negative (201)Tl underwent coronary angiography: 3-vessel CAD was found
      in 3 patients, 2-vessel CAD in 1, coronary spasm in 2, and insignificant lesions
      in 1. In the remaining 7 patients, no cardiac event was observed during 2-year
      follow-up. CONCLUSIONS: In patients showing positive BMIPP despite negative
      (201)Tl, a segmental BMIPP perfusion abnormality indicates a high likelihood for
      CAD, despite normal stress (201)Tl imaging. Thus, adding BMIPP to (201)Tl imaging
      may help to better identify patients with significant CAD, including multivessel
      disease.

PMID- 16434814
TI  - Does high-power computed tomography scanning equipment affect the operation of
      pacemakers?
AB  - BACKGROUND: Computed tomography (CT) is widely used in clinical practice, but
      there has not been a detailed report of its effect on the functioning of
      pacemakers. METHODS AND RESULTS: During CT, ECGs were recorded in 11 patients
      with pacemakers and the electromagnetic field in the CT room was also measured.
      The effect of CT on a pacemaker was also investigated in a human body model with
      and without shielding by rubber or lead. Transient malfunctions of pacemakers
      during CT occurred in 6 of 11 patients. The model showed that malfunctioning of
      the pacemaker was induced by CT scanning and this was prevented by lead but not
      by rubber. The alternating electrical field was 150 V/m on the CT scanning line,
      which was lower than the level influencing pacemaker functions. The alternating
      magnetic field was 15 muT on the CT scanning line, which was also lower than the
      level influencing pacemaker functions. CONCLUSIONS: Malfunctions of the pacemaker
      during CT may be caused by diagnostic radiant rays and although they are
      transient, the possibility of lethal arrhythmia cannot be ignored.

PMID- 16434815
TI  - Initial experiences in management of blunt aortic injury taking associated brain
      injury into consideration.
AB  - BACKGROUND: Although endovascular stent-grafting (SG) has become acceptable for
      blunt aortic injury (BAI), open surgical repair (OR) does provide reliable, good
      long-term results. A current surgical strategy for BAI, taking account of
      associated brain injury, is presented and preferable initial management for BAI
      is proposed. METHODS AND RESULTS: The surgical strategy for BAI was established
      in 2001: SG is performed for patients with obvious brain injuries, but OR is
      performed for patients without brain injury, and conservative treatment should be
      used initially for patients with critical non-aortic injuries. Between 2001 and
      2004 20 patients with BAI were admitted to hospital: 16 blunt aortic ruptures and
      4 blunt aortic dissections. Of them 15 patients underwent surgery (SG, 9; OR, 6)
      and 5 patients were treated conservatively. One patient died from associated lung
      injury after SG, all patients treated conservatively died because of associated
      brain injuries or another rupture of BAI, and 2 elderly patients treated by OR
      died within 1 year from postoperative respiratory failure. CONCLUSION: This brain
      injury conscious surgical strategy for BAI provided acceptable early results. OR
      should be chosen for young patients without brain injury, but endovascular SG
      seems to be a better initial treatment for elderly patients or patients with
      other comorbidities.

PMID- 16434817
TI  - Bepridil inhibits sub-acute phase of atrial electrical remodeling in canine rapid
      atrial stimulation model.
AB  - Background The effect of bepridil, a multichannel blocker, on atrial electrical
      remodeling was evaluated in a canine rapid atrial stimulation model. Methods and
      Results In 10 beagle dogs, the right atrial appendage (RAA) was paced at 400
      beats/min for 2 weeks. The atrial electrophysiological parameters, including
      effective refractory period (AERP), were evaluated at three atrial sites: RAA,
      the right atrium close to the inferior vena cava (IVC) and the left atrium (LA),
      during the time course of rapid pacing. Five of the dogs were given bepridil (10
      mg . kg (-1) . day(-1) po). In the control group, AERP was significantly
      shortened at all atrial sites and the AERP shortening (DeltaAERP) was larger for
      the RAA and LA than at the IVC site (p<0.05). In the bepridil group, DeltaAERP
      was smaller than that of the controls at all atrial sites, and the AERP started
      to return slowly to the pre-pacing level in the second week, regardless of the
      continuation of rapid pacing. Conclusions In a canine rapid atrial stimulation
      model, bepridil suppressed AERP shortening. Bepridil might have a reverse
      electrical remodeling effect, at least for AERP shortening, because it showed
      slow recovery of AERP in the subacute phase of rapid atrial pacing. (Circ J 2006;
      70: 206 - 213).

PMID- 16434816
TI  - Four cases of Kawasaki syndrome complicated with myocarditis.
AB  - BACKGROUND: Myocarditis frequently occurs in the acute phase of Kawasaki syndrome
      (KS), and a few severe cases have been reported. Four cases of myocarditis in KS
      required additional catecholamine treatment because of severe left ventricular
      dysfunction (LVD). CASE REPORTS: Three cases were relatively older children and 2
      cases were complicated with encephalopathy. All 4 developed coronary artery
      abnormalities during convalescence. There was 1 case of LVD because of prolonged
      severe inflammation prior to administration of intravenous immunoglobulin (IVIG).
      The remaining 3 patients had normal values for ejection fraction before the
      administration of IVIG but decreased values (42-51%) and increased C-reactive
      protein levels after IVIG administration. These cases demonstrate an association
      between myocarditis in KS and severe or worsened inflammation. CONCLUSIONS: Even
      with prior normal echocardiography, careful observation of cardiac function may
      be necessary for patients with KS, especially older children, when inflammation
      deteriorates after administration of IVIG.

PMID- 16434818
TI  - Prolapse of aortic intimal flap into the left ventricle: a rare cause of global
      myocardial ischemia in acute type A aortic dissection.
AB  - A 62-year-old woman experienced an acute type A aortic dissection complicated
      with profound shock caused by acute myocardial ischemia. Intraoperative
      transesophageal echocardiography (TEE) identified a circumferentially dissected
      intimal flap at 5.5 cm above the aortic valve, prolapsing into the left ventricle
      through the aortic valve during diastole and obstructing both coronary ostia.
      Acute aortic dissection must be kept in mind when presented with myocardial
      ischemia and TEE is the most useful method for detecting a prolapsing cylindrical
      intimal flap.

PMID- 16434819
TI  - Predictors of angiographic changes in neck remnants of ruptured cerebral
      aneurysms treated with Guglielmi detachable coils.
AB  - The angiographic changes in neck remnants of ruptured cerebral aneurysms treated
      with Guglielmi detachable coils (GDCs) were evaluated in the acute stage to
      analyze the important radiological and clinical factors. The clinical and
      radiological data of 37 patients with a residual neck of a ruptured cerebral
      aneurysm treated with GDC were reviewed. The angiographic changes on follow-up
      angiography were classified into three groups: recanalization of the neck
      remnant, progressive thrombosis, and unchanged. The effects of the clinical and
      angiographic findings, such as patient age, follow-up period, type of aneurysm
      (terminal type or side wall type), dome diameter, neck size, dome/neck ratio,
      obliteration rate, and volume embolization ratio were investigated.
      Recanalization of the neck remnant was observed in 18 of 37 cases, progressive
      thrombosis in nine, and unchanged in 10. The type of aneurysm, dome diameter,
      neck size, and volume embolization ratio were correlated with changes in the neck
      remnant. The aneurysm dome diameter and type of aneurysm were independent
      predictive factors for the recanalization of neck remnants on follow-up
      angiography. Dome diameter of less than 4.5 mm and volume embolization ratio of
      more than 31% in side wall aneurysms were likely to lead to progressive
      thrombosis.

PMID- 16434820
TI  - Clinical study of cerebrospinal fluid dynamics using 111In-DTPA SPECT in patients
      with subarachnoid hemorrhage.
AB  - The ventricle-to-background ratio and clearance rate constant measured by indium
      111 diethylenetriaminepenta-acetic acid single photon emission computed
      tomography ((111)In-DTPA SPECT) were evaluated for predicting hydrocephalus in 16
      patients at 2 to 3 weeks after onset of subarachnoid hemorrhage. The activity in
      the lateral ventricles, basal cistern, and hemispheric convexities was measured
      at 6, 24, and 48 hours after lumbar injection of radionuclide. In the follow-up
      study, eight patients developed hydrocephalus, and required ventriculoperitoneal
      shunting. Radioactivity measured in the hemispheric convexity did not reach peak
      activity within 48 hours. The clearance rate measured by applying the mono
      exponential equation failed to show delayed clearance of radionuclide in
      hydrocephalus. The ratio between the ventricle and basal cistern measured at 6
      hours postinjection was the best predictor of hydrocephalus (F(1, 30) = 42.84, p
      < 0.0001). These results suggest that a single (111)In-DTPA SPECT scan may be
      sufficient to identify patients at risk of developing hydrocephalus.

PMID- 16434822
TI  - Covered stent treatment for traumatic cervical carotid artery aneurysms--two case
      reports.
AB  - A 37-year-old man and a 23-year-old man with cervical carotid artery aneurysms
      were treated with covered stents. The covered stent was constructed from a Palmaz
      stent covered with an expanded polytetrafluoroethylene graft. Angiography showed
      the aneurysms had disappeared immediately after the procedure. Patency of the
      covered stents was confirmed at 18 and 34 months after intervention by three
      dimensional computed tomography angiography. The covered stent allows relatively
      noninvasive reconstruction of the parent artery that immediately brings about
      complete thrombosis of the aneurysm. However, delivering the covered stent to the
      carotid artery may be difficult.

PMID- 16434821
TI  - Interstitial hyperthermia with intra-arterial injection of adriamycin for
      malignant glioma.
AB  - A new method for treating malignant glioma by concurrent intra-arterial injection
      of adriamycin during thermotherapy was performed in seven patients with malignant
      glioma, four males and three females, with five cases of glioblastoma and two of
      anaplastic oligodendroglioma. Adriamycin was intra-arterially injected at a dose
      of 20 mg via the common carotid artery during thermotherapy. The heating
      procedure was repeated three times combined with chemotherapy in one therapy
      course, and a total of nine therapy courses were performed in the seven patients.
      All patients tolerated the protocol well. Based on post-therapy computed
      tomography, five of the therapy courses achieved partial response, one course
      resulted in disease progression, and the remaining three courses showed no
      change. The median time to progression was 3.4 months and the overall median
      length of survival following stereotactic biopsy was 13.2 months. Facial flushing
      was observed during eight therapy courses, and extensive alopecia in six therapy
      courses. Intracystic concentrations of adriamycin were determined in three
      patients, and marked increases were observed. Intra-arterial injection
      chemotherapy during hyperthermia is a promising therapeutic method for treatment
      of malignant glioma with few adverse effects.

PMID- 16434823
TI  - Kissing aneurysms at the junction of the internal carotid artery and the
      ipsilateral duplicate anterior choroidal arteries--case report.
AB  - A 45-year-old woman presented with kissing aneurysms located at the junctions of
      the internal carotid artery and the duplicate anterior choroidal arteries
      manifesting as acute subarachnoid hemorrhage. The aneurysms were clipped during
      temporary occlusion of the internal carotid artery. Surgery for kissing aneurysms
      requires special consideration including analysis of the anatomical relationship
      before clipping, control of premature rupture during clipping, and preservation
      of the patency of the two anterior choroidal arteries after clipping.

PMID- 16434824
TI  - De novo vertebral artery dissecting aneurysm after contralateral vertebral artery
      occlusion--two case reports.
AB  - Two patients developed de novo vertebral artery dissecting aneurysm after
      contralateral vertebral artery occlusion. A 36-year-old man presented with
      brainstem ischemia and was treated non-surgically. Subsequent angiography showed
      spontaneous vertebral artery occlusion at the site of dissection. A 45-year-old
      man developed subarachnoid hemorrhage due to vertebral artery dissecting
      aneurysm. He underwent endovascular occlusion of the vertebral artery proximal to
      the dissecting aneurysm. These patients developed de novo dissecting aneurysm on
      the contralateral vertebral artery at 13 months and 11 days after unilateral
      vertebral artery occlusion, respectively. These cases strongly suggest that
      changes in hemodynamic stress due to unilateral vertebral artery occlusion are
      related to de novo dissecting aneurysm on the contralateral side. The risk of de
      novo dissecting aneurysm may be increased by proximal occlusion or trapping of
      dissecting aneurysm of the contralateral vertebral artery.

PMID- 16434825
TI  - Chordoid meningioma--case report.
AB  - A 69-year-old female presented with a de novo lesion detected incidentally.
      Computed tomography demonstrated an isodense mass in the left parietal convexity
      with peritumoral edema, with homogeneous enhancement by contrast medium. Magnetic
      resonance imaging showed the left parietal convexity tumor as isointense on T(1)
      weighted imaging and homogeneously hyperintense on T(2)-weighted imaging, with
      homogeneous enhancement and dural tail sign after intravenous administration of
      gadolinium-diethylenetriaminepenta-acetic acid. The tumor was totally removed.
      The histological diagnosis was chordoid meningioma. Combined immunohistochemical
      staining was helpful to differentiate chordoid meningioma from other chordoid
      neoplasm.

PMID- 16434826
TI  - Neurocytoma manifesting as intraventricular hemorrhage--case report.
AB  - A 43-year-old man presented with a neurocytoma manifesting as severe headache and
      disturbance of consciousness. Computed tomography revealed intraventricular
      hemorrhage, and a small mass lesion with calcification on the wall of the left
      lateral ventricle. The lesion appeared as mixed intensity regions on both T(1)-
      and T(2)-weighted magnetic resonance imaging, and heterogeneous enhancement with
      gadolinium-diethylenetriaminepenta-acetic acid. Angiography showed the pooling
      sign near the calcification in the late venous phase. Neurologically, amnestic
      syndrome was demonstrated in the subacute phase. Gross total removal of the
      lesion was performed through a transcallosal approach. His transient memory
      disturbance resolved. The histological diagnosis was neurocytoma.
      Intraventricular hemorrhage is rare as the initial presentation of neurocytoma.
      Surgery should avoid fornix injury and the risk of permanent memory disturbance.

PMID- 16434827
TI  - Safe removal of glioblastoma near the angular gyrus by awake surgery preserving
      calculation ability--case report.
AB  - A 67-year-old patient presented with progressive agraphia, alexia, and impaired
      ability to calculate persisting for 4 weeks. He showed preserved ability to do
      single-digit addition and subtraction. Magnetic resonance imaging demonstrated a
      tumor in the left parietal lobe. A malignant glioma was suspected, and awake
      craniotomy was performed to remove the tumor with functional cortical mapping to
      determine the cortices involved in calculation and language. His calculation
      ability was mapped on the angular gyrus, and partial resection of the tumor was
      achieved without deterioration of that ability. The histological diagnosis was
      glioblastoma multiforme. The patient's calculation ability improved dramatically
      after the operation.

PMID- 16434828
TI  - Radiation-induced osteosarcoma 16 years after surgery and radiation for glioma-
      case report.
AB  - A 35-year-old man developed osteosarcoma of the left parietal and occipital bones
      16 years after radiotherapy for glioma in the right occipital lobe. Radiotherapy
      of the primary neoplasm used 50 Gy administered to a localized field through two
      lateral ports. The secondary neoplasm arose contralateral to the primary lesion
      but within the irradiated field. The tumor had a multilocular cyst with
      considerable intracranial extension, and symptoms of elevated intracranial
      pressure were prominent early in the course. After a short-lived initial
      remission following surgical intervention and chemotherapy, the patient
      deteriorated because of tumor recurrence and died 18 months after the diagnosis.
      Radiation-induced osteosarcoma is a well-known but rare complication of
      radiotherapy for brain neoplasms with a poor prognosis.

PMID- 16434829
TI  - Matrix metalloproteinases and hypertension: a link between left ventricular
      hypertrophy and diastolic dysfunction?

PMID- 16434830
TI  - The protective effect of vitamins a and C on endotoxin-induced oxidative renal
      tissue damage in rats.

PMID- 16434832
TI  - Accurate diagnosis of a homozygous G1138A mutation in the fibroblast growth
      factor receptor 3 gene responsible for achondroplasia.
AB  - Achondroplasia is the most common genetic form of dwarfism inherited as an
      autosomal dominant disorder. Individuals affected with achondroplasia have
      impaired ability to form bone from cartilage (endochondral bone formation).
      Homozygous achondroplasia is a neonatal lethal condition. The vast majority of
      patients with achondroplasia have a G-to-A transition at position 1138 of the
      fibroblast growth factor receptor 3 (FGFR3) cDNA sequence, resulting in the Gly
      to-Arg substitution at position 380 of the FGFR3 protein. This mutation has been
      diagnosed by SfcI digestion of amplified genomic DNA. However, it has also been
      demonstrated that the SfcI digestion protocol does not consistently distinguish
      between DNA samples heterozygous and homozygous for the G1138A substitution. This
      study was designed to improve the molecular diagnosis based on the polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP)
      techniques for the FGFR3 G1138A mutation. The newly designed forward primer
      contains one mismatch (G at position 1136) from the FGFR3 cDNA sequence (A at
      position 1136), thereby creating a PstI site (CTGCAG at positions 1134 to 1139)
      in the amplified DNA from alleles containing the G1138A mutation. The PCR-RFLP
      technique based on the PstI digestion of amplified genomic DNA with a novel
      forward primer shows 100% accuracy in diagnosis of the G1138A mutation in
      heterozygous and homozygous individuals.

PMID- 16434833
TI  - Lactation and risk of endometrial cancer in Japan: a case-control study.
AB  - The incidence of endometrial cancer is rapidly increasing in Japan. Although the
      risk factors in European populations have been well described, there are few
      epidemiologic studies regarding risk factors for endometrial cancer in Japanese
      women. This hospital-based case-control study among Japanese women was carried
      out from 1998 to 2000. The cases were selected from women with endometrial cancer
      (n =155), and the controls selected from women attending the university
      gynecological outpatient clinic for cervical cancer screening (n = 96). Subjects
      were interviewed to ascertain breast feeding practices, contraceptive usage, as
      well as potential risk factors for endometrial cancer. We observed a lower risk
      of endometrial cancer associated with oral contraceptive (OC) and a higher risk
      associated with higher body mass index (BMI), and older ages at first and last
      delivery. Gravidity reduced odds ratio (OR) for endometrial cancer to 0.34 (95%
      confidence interval [CI] 0.13-0.92). Compared with parous women who had never
      breastfed, the multivariate OR for women with a history of breastfeeding was 0.37
      (95% CI, 0.17-0.82). Additionally, a greater lapse of time since breastfeeding
      increased OR for endometrial cancer by over three times. In conclusion, the
      present study has indicated that breastfeeding reduces the risk of endometrial
      cancer in Japanese women.

PMID- 16434834
TI  - Contribution of plasma matrix metalloproteinases to development of left
      ventricular hypertrophy and diastolic dysfunction in hypertensive subjects.
AB  - Matrix metalloproteinases (MMPs) are involved in the regulation of the
      extracellular matrix (ECM) of the myocardium and thus the pathogenesis of
      vascular and cardiac hypertrophy. In this study, we investigated contribution of
      plasma matrix metalloproteinases to development of left ventricular hypertrophy
      (LVH) and diastolic dysfunction in hypertensive subjects. Hypertensive patients
      with (n = 27) and without LVH (n = 23) were included. All participants underwent
      a complete transthoracic echocardiographic examination, including recordings of
      the mitral annular early, late, systolic and diastolic velocities by Doppler
      imaging. Plasma concentrations of MMP-3 and MMP-9 were determined by the one-step
      sandwich enzyme immunoassay method. Plasma MMP-3 and MMP-9 concentrations were
      significantly higher in patients with LVH than those without LVH (2.4 +/- 1.2 vs
      1.5 +/- 0.7 ng/ml, p = 0.006 and 5.2 +/- 2.8 vs 3.3 +/- 1.7 ng/ml, p = 0.003,
      respectively). MMP-3 and MMP-9 levels were also correlated with left ventricular
      posterior wall thickness and Doppler indices of diastolic dysfunction. Our
      findings have suggested that increased MMP levels may contribute to LVH and left
      ventricular diastolic dysfunction. Therefore, treatment of hypertension with MMP
      lowering drugs, such as angiotensin converting enzyme inhibitors and angiotensin
      receptor blockers, may have favorable effects on LVH and left ventricular
      diastolic dysfunction.

PMID- 16434835
TI  - Smoking as a risk factor for visceral fat accumulation in Japanese men.
AB  - Epidemiological and clinical studies on the lifestyle-related obesity have
      identified smoking, physical activity and alcohol intake as risk factors for
      obesity. However, no consensus has yet been reached on the effect of smoking on
      visceral adiposity. This study was designed to assess whether smoking is
      associated with the accumulation of visceral fat, glucose and lipid metabolism.
      The subjects were 450 males aged from 24 to 68 years old, who were examined at
      the health control center in the regular health check conducted by their company.
      A self-administered questionnaire was used to ascertain smoking status, daily
      physical activity and alcohol drinking. The number of Brinkman index as an index
      for smoking status was positively related to being visceral fat area (VFA). In
      smokers whose Brinkman index was higher, the percent of subjects with abnormal
      body mass index, VFA, triglyceride, high density lipoprotein-cholesterol,
      atherosclerotic index, plasma glucose, immunoreactive insulin, or homeostasis
      model assessment of insulin resistance (HOMA-IR) was higher than that in non
      smokers. When evaluated in terms of age-adjusted odds ratios for incidence of a
      VFA of 100 cm(2) or greater, alcohol drinking was associated with the highest
      odds ratio. Smoking, physical inactivity and excessive alcohol drinking were
      associated with visceral adiposity, and smoking affected glucose and lipid
      metabolism. In conclusions, these findings suggest that smoking is a risk factor
      for visceral fat accumulation and deterioration of glucose and lipid metabolism.

PMID- 16434836
TI  - Zinc supplementation ameliorates electromagnetic field-induced lipid peroxidation
      in the rat brain.
AB  - Extremely low-frequency (0-300 Hz) electromagnetic fields (EMFs) generated by
      power lines, wiring and home appliances are ubiquitous in our environment. All
      populations are now exposed to EMF, and exposure to EMF may pose health risks.
      Some of the adverse health effects of EMF exposure are lipid peroxidation and
      cell damage in various tissues. This study has investigated the effects of EMF
      exposure and zinc administration on lipid peroxidation in the rat brain. Twenty
      four male Sprague-Dawley rats were randomly allocated to three groups; they were
      maintained untreated for 6 months (control, n = 8), exposed to low-frequency (50
      Hz) EMF for 5 minutes every other day for 6 months (n = 8), or exposed to EMF and
      received zinc sulfate daily (3 mg/kg/day) intraperitoneally (n = 8). We measured
      plasma levels of zinc and thiobarbituric acid reactive substances (TBARS), and
      levels of reduced glutathione (GSH) in erythrocytes. TBARS and GSH levels were
      also determined in the brain tissues. TBARS levels in the plasma and brain
      tissues were higher in EMF-exposed rats with or without zinc supplementation,
      than those in controls (p < 0.001). In addition, TBARS levels were significantly
      lower in the zinc-supplemented rats than those in the EMF-exposed rats (p <
      0.001). GSH levels were significantly decreased in the brain and erythrocytes of
      the EMF-exposed rats (p < 0.01), and were highest in the zinc-supplemented rats
      (p < 0.001). Plasma zinc was significantly lower in the EMF-exposed rats than
      those in controls (p < 0.001), while it was highest in the zinc-supplemented rats
      (p < 0.001). The present study suggests that long-term exposure to low-frequency
      EMF increases lipid peroxidation in the brain, which may be ameliorated by zinc
      supplementation.

PMID- 16434837
TI  - Electrocution-related mortality: a review of 123 deaths in Diyarbakir, Turkey
      between 1996 and 2002.
AB  - Electrical burns are responsible for considerable morbidity and mortality, and
      are usually preventable with simple safety measures. We conducted a retrospective
      study of non-lightening electrocution deaths in Diyarbakir, Turkey between 1996
      and 2002. All 123 deaths investigated were accidental. The age range was 2 to 63
      years with a mean age of 20.7 +/- 15.3 years. Eighty-six victims (69.9%) were
      male. The upper extremity was the most frequently involved contact site in 96
      deaths (48%). No electrical burn mark was present in 14 (11.4%) cases. Home
      accidents were responsible for 56 cases deaths (45.5%). Deaths were caused most
      frequently by touching an electrical wire (52 cases, 42.3%). There was an
      increase in electrocution deaths in the summer (47 cases, 38.2%). One hundred one
      cases (82.1%) were dead on arrival at hospital. The unique findings of our study
      include younger age (0-10 years) of victims (39 cases, 31.7%) and a means of
      electrocution (electrical water heaters in bathroom) in 23 cases (18.7%). Rate of
      deaths due to electrocution among all medicolegal deaths was found higher in our
      study than in previous studies. The public should be educated to prevent children
      to play near electrical appliances and to avoid electrical heaters in the
      bathroom.

PMID- 16434838
TI  - Increased deformability of red blood cells is associated with a deletion
      polymorphism of the angiotensin-converting enzyme gene.
AB  - Angiotensin-converting enzyme (ACE) plays important roles in the renin
      angiotensin system. ACE converts angiotensin I to angiotensin II and also
      inactivates bradykinin, thereby modulating the vascular tone. A polymorphism of
      the ACE gene, located on chromosome 17, has been found in intron 16, and is
      characterized by the presence (insertion [I]) or absence (deletion [D]) of a 287
      base-pair Alu repeat. Individuals with the D allele of the ACE gene have higher
      ACE levels and are at higher risk of cardiovascular events. We aimed to
      investigate the possible relationship between the I/D polymorphism of the ACE
      gene and hemorheological parameters, including red blood cell (RBC)
      deformability. The study was performed on 28 healthy young volunteers (13 women
      and 15 men, mean age 24 +/- 2). The prevalence of the I and D alleles was 30.4%
      and 69.6%, respectively. The I/I genotype (II) was found in 21.4%, I/D genotype
      (ID) in 17.9%, and D/D genotype (DD) in 60.7% of the subjects tested. No
      significant relationship between ACE I/D polymorphism and RBC aggregation or
      whole blood and plasma viscosity was observed. In contrast, RBC deformability was
      significantly increased in the subjects with the DD genotype compared with the II
      (p < 0.05) or the ID (p < 0.01) genotype, and in the subjects with the D allele
      compared with the I allele (p < 0.01). We suggest that RBC deformability of
      individuals with the D allele, who have higher risk for cardiovascular
      pathologies, may have been increased by a compensatory mechanism.

PMID- 16434839
TI  - Osteosarcoma arising from giant cell tumor of bone ten years after primary
      surgery: a case report and review of the literature.
AB  - Giant cell tumor of the bone (GCT) is a relatively uncommon tumor. It is
      characterized by the presence of multinucleated giant cells. GCT is a primary
      benign tumor but may evolve into a malignant tumor, usually after irradiation. We
      report a rare case of osteosarcoma arising ten years after the primary surgery
      for GCT without radiation. A 45-year-old woman presented with severe right knee
      pain after suffering contusion. Roentgenogram revealed a bone tumor in the
      lateral femoral condyle of the right knee. Histopathological examination
      demonstrated the features of GCT, and treatment consisted of curettage and bone
      grafting. Four months after the operation, multiple lung metastases of GCT
      occurred, which were treated by partial lobectomy. Ten years after the primary
      treatment, severe knee pain recurred. Roentgenogram and magnetic resonance
      imaging (MRI) demonstrated a destructive lesion in the lateral condyle of the
      right knee. Histopathological examination demonstrated a lacy pattern of osteoids
      and abnormal mitoses in the aggregated atypical mononuclear cells, indicating
      osteosarcoma. Despite above-knee amputation and chemotherapy, scapular and lung
      metastases developed and the patient died five months after above knee
      amputation. One may question whether the primary GCT contained some malignant
      cells. However, given the aggressiveness of the malignant tumor, this is
      unlikely. The recurrence of pain and aggravation of bone destruction many years
      after the primary treatment suggest malignant transformation of GCT.

PMID- 16434840
TI  - Serum cardiac troponin T in cardiac amyloidosis: serial observations in five
      patients.
AB  - The most common cause of death of patients suffering from amyloidosis is heart
      failure and sudden death, and cardiac troponin T (cTnT), a highly specific and
      sensitive biomarker of myocardial injury, has been reported to be a prognostic
      marker at presentation. But the relationship between serial measurements of serum
      cTnT and clinical course of the disease has not been described. An illustrative
      case was a 55-year-old man with normal renal function presenting with congestive
      heart failure (CHF), whose initial concentration of cTnT was 0.72 ng/ml. Eight
      samples of initial endomyocardial biopsy specimens showed the presence of myocyte
      degeneration and interstitial fibrosis with a small amount of amyloid
      infiltration. However, the cTnT values remained at 0.69 ng/ml after successful
      management of CHF, and four months later, a second endomyocardial biopsy revealed
      diffuse massive amyloid protein deposition. He died of CHF, 9 months after
      initial presentation. In addition, we present 4 cases of amyloidosis with
      increased serum cTnT levels. We therefore propose that serial measurements of
      serum cTnT might be helpful for early diagnosis and prediction of prognosis of
      patients with amyloidosis.

PMID- 16434841
TI  - Diffuse large B-cell lymphoma arising in a patient with neurofibromatosis type I
      and in a patient with neurofibromatosis type II.
AB  - We experienced two unusual cases of diffuse large B-cell lymphoma (DLBCL), which
      occurred in a patient with neurofibromatosis type I and a patient with
      neurofibromatosis type II. B-cell lymphoma is one of the most common phenotypic
      subgroups of malignant lymphoma. Neurofibromatosis I is characterized by cafe-au
      lait spots and neurofibromas. Neurofibromatosis II typically consists of
      bilateral schwannomas of the acoustic nerve. Malignant lymphomas rarely coexist
      with neurofibromatosis I, and no coexistence with neurofibromatosis II has been
      reported. The patient with neurofibromatosis I was a 50-year-old Japanese woman,
      clinically manifesting von Recklinghausen's disease since infancy, who noticed an
      egg-sized tumor in her shoulder. The patient with neurofibromatosis II was a 39
      year-old Japanese man who noticed multiple soft tissue tumors in his neck,
      buttock, and elbow. Biopsied materials from both cases were examined by
      multiparameter methods, including flow cytometry. Flow cytometry revealed large
      scale cells to be tumor cells, and they were positive for CD19, CD20, and CD22.
      Both patients received chemotherapy, and the tumors disappeared. The patient with
      neurofibromatosis I was alive without recurrence at 4 years after treatment,
      while the patient with neurofibromatosis II died of recurrence. To the best of
      our knowledge, this is the first case of malignant lymphoma arising in a
      neurofibromatosis II patient. As for neurofibromatosis I, there were some reports
      about occurrence of malignant lymphoma. It is important to be aware of
      possibility of association of malignant tumors not only of the nervous system but
      also of unrelated to the nervous system when tumors appear in neurofibromatosis
      patients.

PMID- 16434842
TI  - BSE situation and establishment of Food Safety Commission in Japan.
AB  - Eight major policies were implemented by Japanese Government since Oct. 2001, to
      deal with bovine spongiform encephalopathy (BSE). These are; 1) Surveillance in
      farm by veterinarian, 2) Prion test at healthy 1.3mi cows/yr, by veterinarian, 3)
      Elimination of specified risk material (SRM), 4) Ban of MBM for production, sale
      use, 5) Prion test for fallen stocks, 6) Transparent information and
      traceability, 7) New Measures such as Food Safety Basic Law, and 8) Establish of
      Food Safety Commission in the Cabinet Office. At this moment, the extent of SRM
      risk has only been indicated by several reports employing tests with a limited
      sensitivity. There is still a possibility that the items in the SRM list will
      increase in the future, and this indiscriminately applies to Japanese cattle as
      well. Although current practices of SRM elimination partially guarantee total
      food safety, additional latent problems and imminent issues remain as potential
      headaches to be addressed. If the index of SRM elimination cannot guarantee
      reliable food safety, we have but to resort to total elimination of tissues from
      high risk-bearing and BSE-infected animals. However, current BSE tests have their
      limitations and can not yet completely detect highrisk and/or infected animals.
      Under such circumstances, tissues/wastes and remains of diseased, affected fallen
      stocks and cohort animals have to be eliminated to prevent BSE invading the human
      food chain systems. The failure to detect any cohort should never be allowed to
      occur, and with regular and persistent updating of available stringent records,
      we are at least adopting the correct and useful approach as a reawakening
      strategy to securing food safety. In this perspective, traceability based on a
      National Identification System is required.

PMID- 16434843
TI  - Increased phosphorylation of c-Jun NH (2)-terminal protein kinase in the sciatic
      nerves of Lewis rats with experimental autoimmune neuritis.
AB  - The phosphorylation of c-Jun NH (2)-terminal protein kinase (JNK), one of the
      mitogen-activated protein kinases, was analyzed in the sciatic nerves of Lewis
      rats with experimental autoimmune neuritis (EAN). Western blot analysis showed
      that the expression levels of both phosphorylated JNK1 (p-JNK1, approximately 46
      kDa) and phosphorylated JNK2 (p-JNK2, approximately 54 kDa) in the sciatic nerves
      of rats with EAN increased significantly (p < 0.05) at day 14 post-immunization
      (PI) and remained at this level at days 24 and 30 PI, with a slight decrease. In
      EAN-affected sciatic nerves, there was intense immunostaining for p-JNK in the
      infiltrating inflammatory cells (especially ED1- positive macrophages) and
      Schwann cells on days 14-24 PI, compared with those of controls. Some macrophages
      with increased p-JNK immunoreactivity was shown to be apoptotic, while some
      Schwann cells remained survived in this rat EAN model, suggesting that JNK is
      differentially involved in the EAN-affected sciatic nerves. These findings
      suggest that JNK phosphorylation is closely associated with the clearance of
      inflammatory cells as well as the activation of Schwann cells in the EAN affected
      sciatic nerves.

PMID- 16434844
TI  - Histopathological changes of testes and eyes by neutron irradiation with boron
      compounds in mice.
AB  - This study was performed to investigate the biological effects of boron neutron
      capture therapy (BNCT) on the testes and eyes in mice using HANARO Nuclear
      Reactor, Korea Atomic Energy Research Institute. BNCT relies on the high capacity
      of 10B in capturing thermal neutrons. Sodium borocaptate (BSH, 75 ppm, iv) and
      boronophenylalanine (BPA, 750 ppm, ip) have been used as the boron delivery
      agents. Mice were irradiated with neutron (flux: 1.036739E +09, Fluence
      9.600200E+12) by lying flat pose for 30 (10 Gy) or 100 min (33 Gy) with or
      without boron carrier treatment. In 45 days of irradiation, histopathological
      changes of the testes and eyes were examined. Thirty-three Gy neutron irradiation
      for 100 min induced testicular atrophy in which some of seminiferous tubules
      showed complete depletion of spermatogenic germ cells. Lens epithelial cells and
      lens fiber were swollen and showed granular changes in an exposure time dependent
      manner. However, boron carrier treatment had no significant effect on the
      lesions. These results suggest that the examination of histopathological changes
      of lens and testis can be used as "biological dosimeters" for gauging radiation
      responses and the HANARO Nuclear Reactor has sufficient capacities for the BNCT.

PMID- 16434845
TI  - Circadian variations of serum thyroxine, free thyroxine and
      3,5,3'triiodothyronine concentrations in healthy dogs.
AB  - This study was to determine the daily fluctuation of serum thyroxine (tT4), free
      thyroxine (fT4), 3,5,3'-triiodothyronine (T3) concentrations in healthy dogs.
      Thyroid function of these dogs was evaluated on the basis of results of TSH
      response test. Samples for the measurement of serum tT4, fT4, and T3
      concentrations were obtained at 3- hour intervals from 8 : 00 to 20 : 00. Serum
      tT4, fT4, and T3 concentrations were measured by the enzyme chemiluminescent
      immunoassay (ECLIA). Mean T3 concentrations had no significant differences
      according to the sample collection time during the day. Mean tT4 and fT4
      concentrations at 11 : 00 were 3.28 +/- 0.86 microg/dl and 1.30 +/- 0.37 ng/dl,
      respectively and mean tT4 and fT(4) at 14:00 were 3.54 +/- 1.15 microg/dl and
      1.35 +/- 0.12 ng/dl, respectively. These concentrations were significantly high
      compared with tT4 and fT4 concentrations at 8:00, which were 1.75 +/- 0.75
      microg/dl and 0.97 +/- 0.25 ng/dl, respectively (p < 0.05). According to the
      sample collection time, mean tT4 and fT4 concentrations changed with similar
      fluctuation during the day. Based on these results, it was considered that
      measurement of serum tT4 and fT4 concentrations from 11 : 00 to 14 : 00 might
      more easily diagnose the canine hypothyroidism in practice.

PMID- 16434846
TI  - pH-dependent modulation of intracellular free magnesium ions with ion-selective
      electrodes in papillary muscle of guinea pig.
AB  - A change in pH can alter the intracellular concentration of electrolytes such as
      intracellular Ca2+and Na2+ ([Na+]i) that are important for the cardiac function.
      For the determination of the role of pH in the cardiac magnesium homeostasis, the
      intracellular Mg2+ concentration ([Mg2+]i), membrane potential and contraction in
      the papillary muscle of guinea pigs using ion-selective electrodes changing
      extracellular pH ([pH]o) or intracellular pH ([pH]i) were measured in this study.
      A high CO2-induced low [pH]o causes a significant increase in the [Mg2+]i and
      [Na+]i, which was accompanied by a decrease in the membrane potential and twitch
      force. The high [pH]o had the opposite effect. These effects were reversible in
      both the beating and quiescent muscles. The low [pH]o-induced increase in [Mg2+]i
      occurred in the absence of [Mg2+]o. The [Mg2+]i was increased by the low [pH]i
      induced by propionate. The [Mg2+]i was increased by the low [pH]i induced by
      NH4Cl-prepulse and decreased by the recovery of [pH]i induced by the removal of
      NH4Cl. These results suggest that the pH can modulate [Mg2+]i with a reverse
      relationship in heart, probably by affecting the intracellular Mg2+ homeostasis,
      but not by Mg2+ transport across the sarcolemma.

PMID- 16434847
TI  - Analysis of Salmonella enterica serotype Enteritidis isolated from human and
      chickens by repetitive sequence-PCR fingerprinting, antibiotic resistance and
      plasmid profiles.
AB  - A total of 22 Salmonella enterica serotype Enteritidis (S. Enteritidis) strains
      isolated from human and chicken were subjected to DNA fingerprinting by
      repetitive sequence PCR using ERIC and BOX primers, antibiotic resistance and
      plasmid patterns. Both ERIC and BOX PCR amplification data revealed a highly
      genetic homogeneity between isolates from human and chicken except one isolate,
      which originated from chicken and showed a different DNA band pattern from
      others. Eleven of 22 S. Enteritidis isolates (50%) were resistant to more than
      one antibiotics and characterized by 5 resistance patterns. The most common
      pattern was penicillin resistant (63.6%). Only one isolate from chicken showed a
      multiple drug resistance patterns to 4 antibiotics. All 22 S. Enteritidis
      isolates harbored more than two plasmids with eight different plasmid profiles
      including two to six plasmids with approximate molecular size ranging from 1.9 to
      21 kb. A band of 15 kb size was detected in all isolates tested, however, the
      band sizes smaller than 15 kb were found only in isolates from chicken.

PMID- 16434848
TI  - Passive immunization using purified IgYs against infectious bursal disease of
      chickens in Pakistan.
AB  - Infectious bursal disease (IBD) is an acute and highly contagious disease of
      young chickens caused by Birnavirus. Mortality of infected birds can be best
      prevented if injected with antibodies. The present study was an attempt to raise
      specific hyper-immune polyclonal antibodies against IBD virus in Pakistan.
      Commercial layers divided into four groups were injected with IBD vaccine
      subcutaneously according to four different treatment regimens. Eggs were
      collected daily and antibodies were purified from yolk with dextran sulphate.
      Titers of antibodies in serum and yolk were evaluated with enzyme linked
      immunosorbant assay and agar gel precipitation test. Antibody titers were
      significantly higher in yolk than serum. Eggs collected at 28 days post
      vaccination had maximum antibody titers. Of treatment regimens, T3 was found to
      be most effective for hyperimmunization. Lyophilized antibodies stored at 4
      degrees C did not lose their activity till the end of experiment. IBD virus
      infected birds were injected with purified antibodies which induced 92% recovery
      as compared to control birds. The study implicates that the purified antibodies
      may be useful as a therapeutic agent to cure IBD infected birds.

PMID- 16434849
TI  - Concurrent response to challenge infection with Cryptosporidium parvum in
      immunosuppressed C57BL/6N mice.
AB  - We investigated the response to challenge infection with Cryptosporidium parvum
      oocysts in immunosuppressed C57BL/6N mice. In the primary infection, fecal oocyst
      shedding and parasite colonization were greater in immunosuppressed mice than in
      nonimmunosuppressed mice. Compared with primary infection, challenge infection
      with C. parvum didn't show any oocyst shedding and parasite colonization.
      Especially, oocyst shedding and parasite colonization from the mice infected with
      heat-killed oocysts were not detected. After challenge infection with C. parvum
      oocysts, however, these mice were shedding small numbers of oocysts and parasite
      colonization. Except normal control and uninfected groups, the antibody titers of
      other groups appear similar. Based on the fecal oocyst shedding, parasite
      colonization of ilea, and antibody titers in the mice, these results suggest that
      the resistance to challenge infection with C. parvum in immunosuppressed C57BL/6N
      mice has increased.

PMID- 16434850
TI  - Isolation and characterization of Streptococcus sp. from diseased flounder
      (Paralichthys olivaceus) in Jeju Island.
AB  - Streptococcus sp. is gram-positive coccus that causes streptococcal infections in
      fish due to intensification of aquaculture and caused significant economic losses
      in fish farm industry. A streptococcal infection occurred from cultured diseased
      olive flounder (Paralichthys olivaceus) in May, 2005 at a fish farm in Jeju
      Island, Korea. The diseased flounder exhibited bilateral exophthalmic eyes and
      rotten gills; water temperature was 16-18 degrees C when samples were collected.
      Of the 22 fish samples collected, 3 samples were identified as Lactococcus
      garvieae and 18 samples were identified as Streptococcus parauberis by culture
      based, biochemical test. Serological methods such as slide agglutination,
      hemolysis and antimicrobial susceptibility test were also used as well as
      multiplex PCR-based method to simultaneously detect and confirm the pathogens
      involved in the infection. S. parauberis and L. garvieae have a target region of
      700 and 1100 bp., respectively. One fish sample was not identified because of the
      difference in the different biochemical and serological tests and was negative in
      PCR assay. In the present study, it showed that S. parauberis was the dominant
      species that caused streptococcosis in the cultured diseased flounder.

PMID- 16434851
TI  - Some observations on the adaptation of Eimeria tenella (local isolates)
      sporozoites on chicken embryos through chorioallantoic membrane.
AB  - Eimeria (E.) tenella (local isolate) sporozoites were adapted on the
      chorioallantoic membrane (CAM) of 10-12 days chicken embryos and completed its
      life cycle in 6-7 days at 39 degrees C and 70 per cent humidity. Only 23 embryos
      (4.6%) were found dead from 1-4 day post inoculation of sporozoites with mild
      lesions on CAM with no gametocytes but few sporozoites in chorioallantoic fluid
      (CAF). On 5-7 day post inoculation, 432 embryos (86.4%) were found dead with
      severe haemorrhages on CAM and CAF contained uncountable number of gametocytes.
      After seven days post inoculation, 45 embryos (9%) were found to be alive. Some
      oocysts were also detected in the CAF on 6-7 days post inoculation. In the
      histological sections of the CAM, there were abundant small dark colored rounded
      bodies of gametes; distributed extensively in tissues of CAM on 5-7 days post
      inoculation of sporozoites. In some cases, cluster of small mature and immature
      relatively large bodies were seen in increasing numbers on 5-6 days post
      inoculation.

PMID- 16434852
TI  - Parentage testing of Thoroughbred horse in Korea using microsatellite DNA typing.
AB  - The present study was to construct a parentage testing system for Thoroughbred
      (TB) horse. A total number of 1,285 TB horse samples including 962 foals for
      parentage testing, 9 sires and 314 dams for individual identification were
      genotyped. Genomic DNA was extracted from 5 hair roots and genotyped by using 14
      microsatellite markers (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS3, HMS6,
      HMS7, HTG4, HTG10, LEX3 and VHL20). This method consisted of multiplexing PCR
      procedure and showed reasonable amplification of all PCR products. Genotypes were
      determined by genetic analyzer. The number of alleles per locus varied from 3 to
      9 with a mean value of 6.36 in TB horse. The expected heterozygosity was ranged
      from 0.548 to 0.831 (mean 0.699), and the total exclusion probability of 14
      microstellite loci was 0.9998. Of the 14 markers, ASB2, ASB17, ASB23, HMS7 and
      HTG10 loci have relatively high PIC value (> 0.7). Of the 962 foals, 960 foals
      were qualified by compatibility according to the Mendelism. These results suggest
      that the DNA typing method has high potential for parentage verification and
      individual identification of TB horses.

PMID- 16434853
TI  - Practical tips for modified dorsolumbar epidural anesthesia in cattle.
AB  - Segmental dorsolumbar epidural anesthesia has been considered difficult to
      perform. The purpose of this study was to determine whether or not it is
      difficult for beginners to learn how to do modified dorsolumbar epidural
      anesthesia of cattle. Thirty cattle were divided into two groups, young (n = 8)
      and adult (n = 22), according to their age and body weight, and 0.12% new
      methylene blue (NMB) was injected into the first interlumbar (L1.L2) epidural
      space by four fifth-year veterinary school students who had never performed this
      method. After a 1 hour lecture on the modified dorsolumbar epidural anesthesia
      procedure which included basic anatomy and skills, each student successfully
      performed the procedure. In the young group, the NMB solution was distributed
      between the periosteum and the epidural fat (BPF) in one half and between the
      epidural fat and the dura mater (BFD) in the other half of the cattle. In about
      60% (13/22) of the adult group, the NMB solution distributed as BFD type. This
      study showed that the modified dorsolumbar epidural anesthesia procedure is easy
      for beginners to perform if they overcome their fear about the deeper insertion
      of the epidural needle with basic anatomical knowledge and a little experience.

PMID- 16434854
TI  - Guided bone regeneration with beta-tricalcium phosphate and poly L-lactide-co
      glycolide-co-epsilon-caprolactone membrane in partial defects of canine humerus.
AB  - This study was performed to evaluate the effect of betatricalcium phosphate and
      poly L-lactide-co-glycolide-coepsilon- caprolactone (TCP/PLGC) membrane in the
      repair of partial bone defects in canine proximal humerus. Three adult mixed
      breed dogs were used during the experimental period. The length of the defect was
      quarter of the full length of humerus, and width of the defect was quarter of
      middle diameter of the lateral aspect of humerus. The humeri of each dog were
      divided into treatment (TCP/ PLGC) and control groups. The defect was covered
      with TCP/PLGC membrane in treatment group. To evaluate regeneration of the bone,
      computerized tomography (CT) and histopathologic examination were performed. The
      radiopaque lines were appeared at the original defect sites in TCP/PLGC group but
      below the original site in control at 4th week. Radiopacity and thickness of the
      defect sites, and radiopaque lines were more increased at 8th week than those of
      4th week. Histopathologic findings revealed fibrous connective tissue migration
      into the defect and the migration inhibited the structure of new cortex to be
      placed in the original level in control whereas new cortex growth was found in
      the level of original line in TCP/ PLGC group. However, the new cortical bone in
      the TCP/ PLGC group was thinner and less organized than the adjacent intact
      cortex, and the amount of new cancellous bones were also scanty. The result
      suggested that TCP/ PLGC membrane is a good guided bone regeneration material to
      restore the original morphology of humerus in partial defect.

PMID- 16434855
TI  - Influence of ascorbic acid on BUN, creatinine, resistive index in canine renal
      ischemia-reperfusion injury.
AB  - Renal ischemia as a course of renal transplantation is a common cause of renal
      dysfunction as renal failure. The purpose of this study was to investigate the
      influence of ascorbic acid on blood urea nitrogen (BUN), creatinine (Cr) and
      resistive index (RI) for dog models with renal ischemia-reperfusion (I/R) injury.
      Renal ischemia was induced on 6 Beagle dogs. The left kidney was exposed to
      normothermic ischemia for a short period at 30 min followed by reperfusion. On
      the blood Cr level and RI, there was no significant difference comparing both
      groups. 14 days after I/R injury a significant reduction on the blood BUN level
      was observed in the vehicle group (34.06 mg/dl) compared to that of ischemia
      induced treated group (10.3 mg/dl) (p < 0.05). In conclusion, administration of
      ascorbic acid for renal ischemic-reperfusion injury had influence on blood BUN
      level, but it was not revealed the influence on blood Cr and RI.

PMID- 16434856
TI  - Histology of two rice bodies isolated from the stifle of an adult draught horse
      stallion.
AB  - In the human and equine species, different kinds of free floating intra-articular
      particles are related to certain disorders. Osteochondral fragments formed during
      osteochondrosis dissecans are the most common finding in the equine species,
      whereas in humans rice bodies due to rheumatoid arthritis are more frequent.
      Herein we report a third type of floating body inside the stifle of an adult
      draught horse stallion, in macroscopic appearance similar to articular rice
      bodies known in humans. As revealed by histologic examination, the two particles
      consist of polypoid degenerated structures derived from synovial villi. Their
      formation was probably induced by ischemia.

PMID- 16434857
TI  - A hermaphrodite dog with bilateral ovotestes and pyometra.
AB  - Hermaphroditism was identified in a 3-year-old American Cocker spaniel with an
      enlarged os clitoridis that was shown as reddish finger-like structure protruding
      from the vulva. The urethral orifice was located cranially to the base of the os
      clitoridis. The gonads were situated caudal to the kidneys at the cranial tips of
      the uterine horns, and were composed mainly of seminiferous tubules and
      interstitial cells and had ovarian follicles in the cortices. The uterus was
      enlarged and revealed pyometra. Gross and histopathological findings of the dog
      suggested hermaphroditism with bilateral ovotestes and pyometra.

PMID- 16434858
TI  - Malignant ocular melanoma in a dog.
AB  - A mongrel male dog of three years old was referred to the Seoul National
      University Veterinary Teaching Hospital following a one month history of
      glaucoma. On ophthalmic examination, hyphema, glaucoma, uveitis, iridal mass, and
      loss of vision were noted in the right eye. Ultrasonography and computed
      tomography revealed a mass with involvement of the entire uvea. Radiographic
      evaluation did not reveal any evidence of distant metastasis. The right eye was
      surgically removed because of the high likelihood of neoplasia. A histologic
      diagnosis of malignant uveal melanoma was made.

PMID- 16434859
TI  - Grain founder in a male camel (Camelus dromedarius).
AB  - A rare case of laminitis was recorded in an adult camel that was kept in
      confinement without giving any exercise and fed daily with considerable quantity
      of pearl millet grains (Pennisetum typhoideus) for more than five months.

PMID- 16434860
TI  - Application of a temporary palatal prosthesis in a puppy suffering from cleft
      palate.
AB  - A 3-month-old Schnauzer was presented with congenital defects of the secondary
      palate. On the clinical examination, coughing, sneezing, drainage of nasal
      discharge from the external nares and poor growth were found. Vital signs and
      results of blood examination were within normal ranges. Thoracic radiography
      revealed mild pneumonia in the right lung lobes. In a puppy suffering from cleft
      palates, a palatal prosthesis was applied to the hard palate in order to protect
      the surgical wound, because a routine surgery was not successful. A palatal
      prosthesis was applied and held in place using the instant glue and plastic bands
      to protect the surgical wound following the third repeated surgery. Although a
      small oronasal fistula still remained, there was no functional defect. This
      prosthesis was easy to apply and helpful to protect the surgical wound. In
      addition, this implant could be placed or adjusted without or
      sedation/anesthesia.

PMID- 16434862
TI  - [A case of Meckel's diverticulum diagnosed by double balloon enteroscopy].

PMID- 16434861
TI  - Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog.
AB  - A seven-year-old castrated male Yorkshire terrier dog was presented for a
      recurrent skin disease. Erythematous skin during the first visit progressed from
      multiple plaques to patch lesions and exudative erosion in the oral mucosa
      membrane. Biopsy samples were taken from erythematous skin and were diagnosed
      with epitheliotropic T cell cutaneous lymphoma by histopathology and
      immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7
      mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry
      was performed to detect parathyroid hormone-related peptide (PTH-rP) in
      epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not
      labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone
      and isotretinoin. However, the dog died unexpectedly.

PMID- 16434863
TI  - [Biliary cystic neoplasm: biliary cystadenoma and biliary cystadenocarcinoma].
AB  - Biliary cystic tumors, such as cystadenoma and cystadenocarcinoma, are rare
      cystic tumors of liver accounting for fewer than 5% of all intrahepatic cysts of
      biliary origin. Most biliary cystic tumors arise from intrahepatic bile duct and
      10-20% arise from extrahepatic bile duct like common hepatic duct, common bile
      duct, and gallbladder. The first case report of biliary cystic neoplasm in Korea
      dated back to 1975 by Bae et al, and over 40 cases of cystadenoma and 35 cases of
      cystadenocarcinoma were reported since then. These tumors usually present in
      middle-aged women with a mean age of 50 years. Biliary cystadenomas are lined by
      single layer of cuboidal or columnar epithelium and are very often multilocular
      with septal or papillary foldings. Over 80% of cystadenoma have dense mesenchymal
      stroma composed of dense spindle cells, like ovary. The epithelial lining of
      cystadenocarcinoma exhibits cellular atypia, mitotic activity, and infiltrative
      growth, but part of lining epithelium retain the feature of cystadenoma, which
      support the adenoma-carcinoma sequence. The size of tumors varies from 1.5 to 35
      cm. Many patients are asymptomatic, except for the presence of palpable mass.
      When symptoms are present, they include epigastric or right upper quadrant pain
      or jaundice by enlarged mass. Biliary cystic tumor should be considered when a
      single or multilocular cystic lesion with papillary infoldings is detected in the
      liver by computed tomogram (CT) or ultrasound (US). Cystic wall and internal
      foldings can be seen enhanced by enhanced CT. US reveals a hypoechoic cystic mass
      with echogenic septation or papillary infoldings. Cystadenocarcinoma should be
      suspected when there is elevated mass or nodule in the wall or foldings, or
      thickened cystic wall on CT or US. But it is extremely difficult to differentiate
      between cystadenoma and cystadenocarcinoma by imaging alone. Increased tumor
      markers, carcinoembryonic antigen and carbohydrate antigen 19-9, in serum or
      cystic fluid have been reported in biliary cystic tumor. But tumor markers cannot
      distinguish cystadenocarcinoma from cystadenoma or both from other cystic lesions
      of liver. Malignant cells are not usually recovered in patients with
      cystadenocarcinoma who underwent cystic fluid cytology before and during surgery.
      The treatment of choice is radical excision of the mass by means of lobectomy or
      wide tumor excision. Aspiration, marsupialization, and drainage must be avoided.
      Inadequate excision of both cystadenoma and cystadenocarcinoma may lead to
      recurrence. Prognosis after complete excision is excellent.

PMID- 16434864
TI  - [A randomized, prospective, comparative, multicenter study of rabeprazole and
      ranitidine in the treatment of reflux esophagitis].
AB  - BACKGROUND/AIMS: This study was done to evaluate the efficacy of rabeprazole
      (proton-pump-inhibitor) and ranitidine (H(2)-receptor antagonist) in the symptom
      relief and treatment of erosive esophagitis diagnosed by endoscopy. METHODS: A
      total of 110 patients with typical gastroesophageal reflux disease (GERD)
      symptoms were enrolled in this multicenter study. They were randomized into
      rabeprazole group (53 patients) and ranitidine group (57 patients) respectively.
      The patients in rabeprazole group were given 10 mg of rabeprazole and ranitidine
      group received 300 mg of ranitidine before breakfast and dinner for 8 weeks.
      After the end of treatment, we evaluated the endoscopic healing rate of reflux
      esophagitis and symptomatic improvement. RESULTS: After 8 weeks of treatment,
      rabeprazole group showed significantly higher complete endoscopic cure rate than
      ranitidine group (86.8% [46/53] vs. 57.9% [33/57], p=0.001) and higher
      symptomatic improvement of heartburn (91.2% [31/34] vs. 76.2% [32/42], p=0.085),
      especially in the first 7 days (76.7% vs. 45.3%, p=0.008). Also, rabeprazole
      group showed significantly higher improvement of regurgitation symptom than
      ranitidine group (100% [35/35] vs. 83% [39/47], p=0.009). Both group showed no
      differences in the improvement of chest pain and globus sensation. All the
      adverse events (rabeprazole group 4 events vs. ranitidine group 3 events) were
      mild and there was no abnormality in laboratory test. CONCLUSIONS: In patients
      with GERD, rabeprazole 10 mg b.i.d. is superior to ranitidine 300 mg b.i.d. in
      healing of reflux esophagitis and resolving typical GERD symptoms. Rabeprazole is
      an effective and well-tolerated drug for GERD treatment.

PMID- 16434865
TI  - [Is C3435T polymorphism of MDR1 related to inflammatory bowel disease or
      colorectal cancer in Korean?].
AB  - BACKGROUND/AIMS: Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein in
      intestinal epithelium, which serves as a transmembrane efflux pump of various
      toxins. mdr1 knockout mice develop spontaneous colitis under specific pathogen
      free conditions. However, it is unclear that C3435T polymorphism of MDR1 is
      related to ulcerative colitis. Other studies suggest MDR1 may have an important
      role in colorectal carcinogenesis. Thus, we evaluated whether MDR1 C3435T
      polymorphism is present in Korean and it is associated with inflammatory bowel
      disease or colorectal cancer. METHODS: The genotype distributions of the C3435T
      polymorphism were investigated by PCR-RFLP method in 94 patients with ulcerative
      colitis, 24 patients with Crohn's disease, 64 patients with colorectal cancer and
      each of gender-matched controls with equal numbers. RESULTS: There was no
      significant difference in frequencies of 3435T allele and 3435TT genotype between
      patients with ulcerative colitis and controls (p=0.443, p=0.194). No significant
      difference was present in frequencies of 3435T allele and 3435TT genotype between
      patients with Crohn's disease and controls (p=0.378, p=1.000). There was neither
      significant difference in frequencies nor 3435T allele or 3435TT genotype between
      patients with colorectal cancer and controls (p=0.250, p=0.211). C3435T genotype
      was not associated with the age of onset or other clinical characteristics in
      patients with ulcerative colitis, Crohn's disease or colorectal cancer.
      CONCLUSIONS: MDR1 C3435T polymorphism is also present in Korean and the dominant
      allele is C. However, there is no evidence that C3435T polymorphism of MDRI is
      associated to inflammatory bowel disease or colorectal cancer in Korean.

PMID- 16434866
TI  - [Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori
      eradication].
AB  - BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of
      Helicobacter pylori (H. pylori) eradication failure. This study evaluated the
      eradication rate, tolerability, and compliance of levofloxacin- azithromycin
      combined triple therapy for H. pylori eradication. METHODS: 1) First-line
      eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen
      military men in Armed Forces Capital Hospital were treated with 7 days of
      levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid,
      levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk
      Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole
      20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2)
      Second-line eradication: A consecutive series of 59 patients who failed H. pylori
      eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital
      were randomized to two groups. Thirty patients were retreated with 7 days of
      bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid,
      metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients
      were retreated with levofloxacin-azithromycin combined triple therapy. Patient's
      compliance and tolerability were evaluated at the end of treatment. The status of
      H. pylori infection was assessed 8 weeks later then. The successful eradication
      of H. pylori was defined as negative results from histology and CLO test, or 13C
      urea breath test. RESULTS: First-line eradication rate of levofloxacin
      azithromycin triple therapy was lower than that of standard PPI-based triple
      therapy, but there was no statistically significant difference (70.6% vs. 80.3%,
      p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined
      triple therapy was significantly lower than that of bismuth-based quadruple
      therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all
      patients were more than 85%. Two of patients with levofloxacin-azithromycin
      combined triple therapy complained self-limiting side effects (mild dizziness;
      mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin
      combined triple therapy should not be recommended as the first-line or second
      line H. pylori eradication regimen in Korea.

PMID- 16434867
TI  - [Clinical characteristics of intussusception in children: comparison between
      small bowel and large bowel type].
AB  - BACKGROUND/AIMS: Small bowel intussusception is rarely diagnosed in children. And
      its studies have not been frequently reported. While surgical treatment has been
      considered as standard treatment in small bowel intussusception in adult
      population, spontaneous reduction of it is increasingly reported recently.
      Therefore, we analyzed the clinical features and outcome of small bowel
      intussusception in children compared with ileocolic intussusception. METHODS: 95
      children with the diagnosis of intussusception who visited Sanggye-Paik hospital
      were included in this study between March 2000 and December 2003. We
      retrospectively reviewed the clinical records and imaging findings.
      Ultrasonographic studies were performed by an experienced pediatric radiology
      staff using SEQUOIA 512 machine (probe 4-8 MHz). RESULTS: A total of 80 patients
      with ileocolic intussusception (41 male, 39 female) and 15 patients (11 male, 4
      female) with small bowel intussusception were diagnosed. Children with small
      bowel intussusception were older than ileocolic intussusception (mean age: 40
      months vs. 16 months). The presenting symptoms of small bowel intussusception
      were vomiting, irritability, abdominal pain, bloody stool, and abdominal mass in
      order and were not different with those of ileocolic intussusception. While in
      ileocolic intussusception group, reduction was done by gastrograffin enema
      (73.8%), spontaneous reduction (0%) and surgical reduction (26.3%), spontaneous
      reduction was done in 73.3% and surgical reduction in 20% in small bowel
      intussusception group. CONCLUSIONS: Small bowel intussusception in children
      occurred in older age than ileocolic intussusception and was reduced
      spontaneously in large proportion.

PMID- 16434868
TI  - [Clinical and biochemical parameters of nutrition to predict hepatic
      encephalopathy in cirrhotic patients].
AB  - BACKGROUND/AIMS: Protein-calorie malnutrition is a common complication in
      cirrhosis. Protein restriction for the treatment of hepatic encephalopathy (HE)
      may cause disease progression and poor prognosis. Therefore, we evaluated
      important clinical parameters for nutritional state in cirrhotic patients with or
      without HE to predict the development of HE. METHODS: Twenty-two cirrhotic
      patients were divided into two groups; group A-13 patients without HE and group B
      9 patients with HE. Clinical and biochemical parameters, serum proteins {serum
      albumin, insulin-like growth factor-1 (IGF-1), transferrin, leptin, etc},
      immunologic parameters and anthropometry were measured. RESULTS: Child-Pugh score
      and Model for End-stage Liver Disease (MELD) scale were higher in group B
      (p<0.01). After correction of various factors affecting nutritional assessment,
      especially of Child-Pugh score and MELD scale, leptin was higher in group B
      (p<0.05). There was no difference in anthropometric measurements. Transferrin
      correlated inversely with MELD scale in group A (p<0.01). IGF-1 correlated
      inversely with total lymphocyte count in group B (p<0.05). Leptin correlated with
      Child-Pugh scores, total lymphocyte count and mid-arm muscle circumference in
      group A (p<0.05, p<0.05 and p<0.05, respectively), and correlated inversely with
      CD8 in group B (p<0.05). CONCLUSIONS: Leptin level is higher in patients with HE,
      and further studies for parameters of nutrition to predict HE in many cirrhotic
      patients will be needed.

PMID- 16434870
TI  - [A Case of Cronkhite-Canada syndrome showing resolution with Helicobacter pylori
      eradication and omeprazole].
AB  - We describe a 58-year-old woman who was incidentally found to have gastric and
      colonic polyposis, hypoalbuminemia, cutaneous hyperpigmentation and
      onychodystrophy (Cronkhite-Canada syndrome). Histology of polyps from the stomach
      showed features of juvenile or retention type (hamartomatous) polyps with
      Helicobacter pylori (H. pylori) infection. The large pedunculated colonic polyps
      showed hamartomatous polyps with adenomatous component and polypectomy was
      performed. After the treatment with H. pylori eradication and omeprazole, the
      gastric polyposis, hypoalbuminemia and anemia regressed, and endoscopic
      polypectomy of gastric polyps were performed. After the continuous use of
      omeprazole for 14 months, the patient showed complete resolution of clinical
      features of Cronkhite-Canada syndrome. The experience of this case suggests that
      eradication of H. pylori and proton pump inhibitor treatment might be considered
      in patients with gastric polyposis combined with Cronkhite-Canada syndrome.

PMID- 16434869
TI  - [Significances of serum level and immunohistochemical stain of CA19-9 in simple
      hepatic cysts and intrahepatic biliary cystic neoplasms].
AB  - BACKGROUND/AIMS: In spite of various diagnostic modalities, biliary cystic
      neoplasms (biliary cystadenoma and cystadenocarcinoma) remain to be difficult to
      diagnose preoperatively. Recently, there are some reports that elevated CA19-9
      level in serum and/or cystic fluid could be a useful finding in the differential
      diagnosis of biliary cystic neoplasm. This study aimed to evaluate the expression
      of CA19-9 and to elucidate its significances in intrahepatic biliary cystic
      neoplasms and simple hepatic cysts. METHODS: In 8 patients with biliary cystic
      neoplasms and 6 simple hepatic cysts, symptoms, radiologic and laboratory
      findings were reviewed retrospectively. In 5 biliary cystic neoplasms (4 biliary
      cystadenomas, 1 biliary cystadenocarcinoma) and 5 simple hepatic cysts,
      immunohistochemical stainings for CA19-9 were performed with formalin-fixed,
      paraffin-embedded tissues. RESULTS: In 8 biliary cystic neoplasms, two cases were
      suspected as biliary cystadenoma preoperatively and 6 cases could not be
      distinguished from simple cysts or cholangiocarcinoma preoperatively. In 6 simple
      hepatic cysts, 3 cases were diagnosed preoperatively and 3 cases could not be
      distinguished from biliary cystadenoma or pancreatic pseudocyst preoperatively.
      Expression of CA19-9 in simple hepatic cysts and biliary cystic neoplasms were
      80% in both groups. Expression of CA19-9 is not related to the elevated level of
      CA19-9 in serum. CONCLUSIONS: Our data suggests that the elevated level of CA19-9
      in serum may not be helpful in the preoprative diagnosis of biliary cystic
      neoplasm.

PMID- 16434871
TI  - [Two cases of acute hepatitis E in patients with hyperthyroidism].
AB  - Acute hepatitis E occur commonly as outbreaks in endemic areas, but can occur
      sporadically in other part of the world. Acute hepatitis E has been reported
      rarely in Korea. A case of concurrent acute hepatitis E virus (HEV) infection and
      hyperthyroidism was reported in an inactive hepatitis B surface antigen carrier.
      We experienced two cases of concomitant acute HEV infection in patients with
      hyperthyroidism. The first case had acute HEV infection with subclinical
      hyperthyroidism while taking propylthiouracil. The second case suffered from
      acute HEV infection in a patient with Graves' disease intractable to
      propylthiouracil. Herein, we suggest the possible association between HEV
      infection and hyperthyroidism.

PMID- 16434872
TI  - [A case of acute cholecystitis secondary to hemobilia after percutaneous liver
      biopsy].
AB  - Percutaneous liver biopsy is well established for the diagnosis and follow-up of
      many liver diseases. Although it is rather safe, major complications, such as
      bleeding into the peritoneal or thoracic cavity, hemobilia, enteric perforation
      and intrahepatic hematoma, have been reported related to the procedure. Recently,
      incidence of such major complications has been decreased since the introduction
      of ultrasonography-guided liver biopsy. We report a case of 59-year-old female
      patient with acute cholecystitis secondary to hemobilia 2 days after
      ultrasonography-guided percutaneous liver biopsy.

PMID- 16434873
TI  - [A case of leiomyoma in the common bile duct].
AB  - Leiomyomas, originating in the bile duct, are very rare, and only few cases have
      been reported in the literature. We experienced a case of leiomyoma of the distal
      common bile duct, mimicking bile duct cancer. A 39-year-old woman presented with
      intermittent jaundice and general weakness for three months. Clinical profiles
      showed obstructive jaundice, and the abdominal computed tomography and
      cholangiography revealed diffuse bile duct dilatation with distal common bile
      duct stricture. A pylorus-preserving pancreaticoduodenectomy was performed and
      the pathologic specimen disclosed leiomyoma of the common bile duct accompanying
      severe fibrosis. This is the first case of leiomyoma in the bile duct reported in
      Korea.

PMID- 16434874
TI  - [The effect of antibiotic resistance on the eradication of Helicobacter pylori].

PMID- 16434876
TI  - A slow disengagement from platinum-based chemotherapy for patients with advanced
      non-small cell lung cancer.

PMID- 16434877
TI  - Tumor regression by expression of high physiological levels of EBV latent
      membrane protein 1.
AB  - Induction of apoptosis in tumor cells is one of therapeutic strategies of cancer.
      Previous studies indicate that LMP-1 can act as governor of cell proliferation
      because overexpression of latent membrane protein 1 (LMP-1) of Epstein-Barr virus
      (EBV) inhibits cell proliferation. Here we demonstrate that overexpression of the
      NLMP-1, isolated from an EBV strain prominent in Taiwanese population, also
      possess the ability to induce apoptosis of cells, and inhibit CT-26 tumor growth
      in mice. Mapping studies indicate that NLMP-1 transmembrane domain is required
      for induction of cytotoxicity. Intratumoral delivery of vectors expressing NLMP-1
      or its membrane domain via electroporation induces tumor tissue damage,
      suppresses tumor growth in mice, and prolongs the survival of treated animals. In
      addition, the membrane domain of NLMP-1 alone induces effects similar to those
      induced by cotreatment with NLMP-1 and IL-12. Tumor-free mice at 120 days after
      the initial treatments were further challenged with CT-26 tumor cells. No tumor
      growth was observed. Thus, NLMP-1, and more specifically the transmembrane domain
      of NLMP-1, may be promising new therapeutic agents for control of tumor growth.

PMID- 16434878
TI  - Automated cell lineage construction: a rapid method to analyze clonal development
      established with murine neural progenitor cells.
AB  - Understanding cell lineage relationships is fundamental to understanding
      development, and can shed light on disease etiology and progression. We present a
      method for automated tracking of lineages of proliferative, migrating cells from
      a sequence of images. The method is applicable to image sequences gathered either
      in vitro or in vivo. Currently, generating lineage trees from progenitor cells
      over time is a tedious, manual process, which limits the number of cell
      measurements that can be practically analyzed. In contrast, the automated method
      is rapid and easily applied, and produces a wealth of measurements including the
      precise position, shape, cell-cell contacts, motility and ancestry of each cell
      in every frame, and accurate timings of critical events, e.g., mitosis and cell
      death. Furthermore, it automatically produces graphical output that is
      immediately accessible. Application to clonal development of mouse neural
      progenitor cells growing in cell culture reveals complex changes in cell cycle
      rates during neuron and glial production. The method enables a level of
      quantitative analysis of cell behavior over time that was previously infeasible.

PMID- 16434879
TI  - ESCRTing cell proliferation off the beaten path: lessons from the drosophila eye.
AB  - A series of recently published studies have established that defects in endocytic
      sorting can elicit dramatic tissue overgrowth phenotypes in developing organs of
      the fruit fly Drosophila melanogaster. Such a link had been suggested by
      mammalian cell culture experiments almost ten years ago, but in vivo evidence of
      this link, and the mechanisms through which it might occur, had remained elusive.
      Drosophila has now proven to be an excellent developmental system in which to
      both document the effects of endocytic defects on tissue growth and patterning,
      and to probe the basis of these phenotypes. This work has begun to illuminate
      some surprising connections between the endocytic trafficking of protein cargoes
      and the control of cell proliferation and tissue architecture. These connections
      touch major cell biological processes, including cell division, growth, death,
      and polarity, and have begun to paint a complex, yet intriguing, picture of how
      defective endocytic sorting can affect developing tissues.

PMID- 16434880
TI  - p63: a new link between senescence and aging.
AB  - Cellular senescence is a distinctive form of cell cycle arrest that has been
      suggested to modulate the processes of tumor suppression and aging. Though a
      detailed understanding of the cellular machinery regulating this process is
      emerging, a more thorough understanding of the key players linking senescence to
      organismal aging is needed. The recent discovery that loss of the p53-related
      protein p63 induces cellular senescence and causes features of accelerated aging
      provides further evidence that cellular senescence is intimately linked with
      organismal aging, and identifies p63 as a key regulator of both of these
      processes.

PMID- 16434881
TI  - Activating Ras mutations fail to ensure efficient replication of adenovirus
      mutants lacking VA-RNA.
AB  - Adenoviruses lacking their PKR-antagonizing VA RNAs replicate poorly in primary
      cells. It has been suggested that these virus recombinants still replicate
      efficiently in tumor cells with Ras mutations and might therefore be useful in
      tumor therapy. The ability of interferon-sensitive viruses to grow in Ras-mutant
      tumor cells is generally ascribed to a postulated inhibitory effect of mutant Ras
      on PKR. We have constructed a set of isogenic adenoviruses that lack either or
      both VA RNA species, and tested virus replication in a variety of cell species
      with different Ras status. In tendency, VA-less viruses replicated with higher
      efficiency in Ras-mutant cells, as compared to cell lines without Ras mutation.
      However, several exceptions to this rule were observed, arguing against a direct
      inhibition of PKR by mutant Ras. Phosphorylation of the PKR-substrate eIF2alpha
      was observed regardless of the Ras mutational status, upon infection with VA-less
      adenoviruses in the presence of interferon, but also upon addition of the PKR
      activator polyIC to cells. When comparing two isogenic cell lines that differ
      solely with regard to the presence or absence of mutant Ras, no difference was
      observed concerning the replication of VA-less adenoviruses or the
      phosphorylation of eIF2alpha. We conclude that mutant Ras does not directly
      affect eIF2alpha phosphorylation or the replication of interferon-sensitive
      adenoviruses. These results strongly suggest that the Ras mutational status is
      insufficient to predict the oncolytic effect of interferon-sensitive viruses. We
      propose that Ras mutations predispose tumor cells to undergo secondary changes
      that sometimes enable the replication of interferon-sensitive viruses.

PMID- 16434882
TI  - Misregulated chromosome condensation in MCPH1 primary microcephaly is mediated by
      condensin II.
AB  - Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder
      characterized by marked reduction in brain size and mental retardation. Mutations
      in the gene MCPH1, encoding microcephalin, cause MCPH and a unique cellular
      phenotype with premature chromosome condensation in early G2 phase and delayed
      decondensation post mitosis. Here, we show that in MCPH1 patient cells, siRNA
      mediated depletions of condensin II subunits lead to a pronounced reduction of
      cells with the condensation defects in both G1 and G2 phases of the cell cycle.
      Similar results are obtained when microcephalin and condensin II are
      simultaneously depleted in HeLa cells. In contrast, depletions of condensin I
      subunits do not reverse the cellular phenotype. Consistently, condensin I stays
      in the cytoplasm in the prophase-like cells of MCPH1 patients. Our results offer
      a molecular explanation for the aberrant chromosome condensation in MCPH1
      deficiency and provide additional evidence that condensin I and II are regulated
      by distinct pathways.

PMID- 16434883
TI  - Identification of novel targets of MYC whose transcription requires the essential
      MbII domain.
AB  - The MYC oncoprotein is among the most potent regulators of cell cycle progression
      and malignant transformation in human cells. Current models suggest that much of
      MYC's role in these processes is related to its ability to regulate the
      transcription of downstream target genes that encode the ultimate effector
      proteins. In addition to its carboxy-terminal DNA binding and dimerization
      domains, an enigmatic motif in the amino terminus termed MbII is required for all
      of MYC's biological activities. In spite of historical observations demonstrating
      the absolute requirement for MbII in these biological functions, clues
      implicating this domain in target gene transcription have only recently appeared.
      Based on this emerging link between MbII and transcriptional activation, we
      hypothesized that the identification of individual MYC targets whose
      transactivation requires MbII would help define the essential downstream
      effectors of MYC in transformation and cell cycle progression. In hopes of
      directly identifying new MbII-dependent MYC target genes, an expression profiling
      screen was conducted. This screen resulted in our identification of ten novel
      downstream targets of MYC. As a proof of principle, we recently demonstrated
      using RNAi-mediated depletion that one of these targets, the metastasis regulator
      MTA1, is absolutely required for MYC mediated transformation. Here we report the
      identity of these previously uncharacterized MYC targets and discuss their
      potential roles in MYC function. In addition, we attempt to reconcile the
      historical and contemporary evidence linking MbII to transcriptional activation.

PMID- 16434884
TI  - Measures of sexual partnerships: lengths, gaps, overlaps, and sexually
      transmitted infection.
AB  - GOAL: The length of time between partnerships ("gap") is an important determinant
      of the overall transmission system of sexually transmitted infections. We
      describe the distributions of gaps, lengths, and overlaps among participants in a
      random-digit dialing survey conducted among 1194 Seattle residents during 2003
      2004. METHODS: Survey participants were restricted to those 18 to 39 years of age
      with fluency in the English language. We limited our analysis to the 1051 (88%)
      participants who reported ever engaging in vaginal, oral, or anal intercourse and
      reported information on gaps, lengths, and overlaps. RESULTS: Most (59%) observed
      gaps between partnerships were of length<or=6 months; therefore, the majority of
      18- to 39-year-olds seeking new partners find a new partner well within the
      infectious period of chlamydia infection, gonorrhea, and syphilis (if no
      treatment is received) and herpes simplex virus, human papilloma virus, and human
      immunodeficiency virus infections. This was generally true independent of gender,
      race, income, or education. Gap length, however, correlated with age.
      CONCLUSIONS: The observed shorter gap lengths among younger individuals reinforce
      the need to focus interventions on adolescents and young adults, particularly
      those with the potential to mix with infected individuals.

PMID- 16434885
TI  - The cost-effectiveness of an outreach clinical model in the management and
      prevention of gonorrhea and chlamydia among Chinese female sex workers in Hong
      Kong.
AB  - BACKGROUND: Social marginalization and stigmatization in usual medical care
      setting may refrain female sex workers (FSWs) from seeking usual medical care for
      sexually transmitted infections in Hong Kong. GOAL: To evaluate the cost
      effectiveness of using an outreach approach for treatment and prevention of
      gonorrhea and chlamydia among FSWs. STUDY DESIGN: A decision tree was designed to
      simulate the outcomes of 2 alternatives: (1) outreach service providing treatment
      of gonorrhea and chlamydia and counseling to FSWs (outreach arm) and (2) no
      outreach service (control arm). Five tiers of outcomes were estimated for each
      study arm: (1) total direct medical cost, (2) number of FSWs infected with
      gonorrhea, (3) number of new cases of gonorrhea in clients transmitted by FSWs,
      (4) number of FSWs infected with chlamydia, and (5) number of new cases of
      chlamydia in clients transmitted by FSWs. Clinical inputs were estimated from
      literature, and cost analysis was conducted from the perspective of a public
      health organization. RESULTS: Compared to the control group, the marginal savings
      per new case of infection averted (marginal cost divided by marginal cases of
      infection) of the outreach group were $10,988 (US dollars) per case of gonorrhea
      averted in FSWs, $685 per case of gonorrhea averted in clients, $9643 per case of
      chlamydia averted in FSWs, and $220 per case of chlamydia averted in clients
      ($1=7.8 Hong Kong dollars). CONCLUSIONS: An outreach clinic is potentially less
      costly and more effective in preventing transmission of gonorrhea and chlamydia
      between FSWs and their clients in Hong Kong.

PMID- 16434886
TI  - Associations between substance use and sexual risk among very young men who have
      sex with men.
AB  - OBJECTIVE: To determine if an association exists in young men who have sex with
      men (MSM) between being under the influence of alcohol or drugs during sex and
      participation in sexual behaviors which increase the risk of human
      immunodeficiency virus (HIV). STUDY DESIGN: A total of 3492 young MSM were
      interviewed through the Young Men's Survey, an anonymous, cross-sectional,
      multisite, venue-based survey conducted from 1994 through 1998 at 194 public
      venues frequented by MSM aged 15 to 22 years in 7 US cities. RESULTS: The
      majority of young MSM reported both receptive and insertive anal intercourse, and
      of these, approximately half reported not using condoms. Report of unprotected
      receptive anal intercourse at least once in the prior 6 months was associated
      with being under the influence of alcohol (adjusted odds ratio [AOR]=1.5; 95%
      confidence interval [CI]=1.2-1.8), cocaine (AOR=1.6; 95% CI=1.1-2.2),
      amphetamines (AOR=1.5; 95% CI=1.1-2.0) or marijuana during sex (AOR=1.3; 95%
      CI=1.1-1.6). Report of unprotected insertive anal intercourse at least once in
      the prior 6 months was associated with being under the influence of alcohol
      (AOR=1.2; 95% CI=1.0-1.5), cocaine (AOR=1.5; 95% CI=1.1-2.0) or amphetamines
      (AOR=1.9; 95% CI=1.4-2.6). CONCLUSIONS: HIV prevention strategies for young MSM
      need to incorporate substance use risk reduction.

PMID- 16434887
TI  - Spectrum of epithelial neoplasms in end-stage renal disease: an experience from
      66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those
      in sporadic adult renal neoplasia.
AB  - Most (up to 71%) of renal cell neoplasms occurring in patients with end-stage
      renal disease (ESRD), particularly with acquired cystic disease of the kidney
      (ACDK), have been reported to be papillary renal cell carcinoma (RCC). Our
      initial experience with tumors in such a setting indicated that many tumors were
      histologically difficult to classify into the known subtypes of RCC or had
      features that were different from those in sporadically occurring RCCs. In this
      study on 66 ESRD kidneys (52 of which showed features of ACDK) removed because
      tumors were detected in them, we found two major groups of RCC. Overall, there
      were 261 grossly identified tumors in these kidneys, and many additional tumors
      were observed on microscopic evaluation in some. Of the two major groups of RCCs,
      one consisted of tumors similar to those seen in sporadic settings (ie, clear
      cell, papillary, and chromophobe RCC), and these formed the dominant mass in 12
      (18%), 10 (15%), and 5 (8%) of the 66 kidneys, respectively. The other group
      consisted of two subtypes of RCC that appear quite unique to ESRD. The more
      common tumor that we have designated as "acquired cystic disease-associated RCC"
      was seen as the dominant mass in 24 (36%) of 66 of the kidneys, and it formed the
      most common tumor type among the smaller nondominant masses, as well. It was
      characterized by a typical microcystic architecture, eosinophilic cytoplasm with
      Fuhrman's grade 3 nuclei, and frequent association with intratumoral oxalate
      crystals. Additionally, these tumors frequently, but usually focally, exhibited
      papillary architecture, and clear cytoplasm. These tumors occurred only in
      kidneys with ACDK, and not in noncystic ESRD. The other category was "clear-cell
      papillary RCC of the end-stage kidneys," present as the dominant mass in 15 (23%)
      of the 66 kidneys and occurring in both the ACDK and noncystic ESRD. These
      predominantly cystic tumors showed prominent papillary architecture with purely
      clear-cell cytology. Immunohistochemical studies in tumors with histology similar
      to the known subtypes of sporadic RCC showed immunoprofiles similar to that
      reported in sporadically occurring tumors. The two subtypes of RCC unique to ESRD
      had distinctive immunoprofiles supporting their separate morphologic
      subcategorization. Only the acquired cystic disease-associated RCC showed lymph
      node metastases in 2 cases and sarcomatoid features in 2 more cases. One of the
      latter 2 died with widespread metastatic disease within 34 months of nephrectomy.
      Thus, a broad spectrum of renal cell tumors exist in ESRD, only some of which
      resemble the sporadic RCCs. Acquired cystic disease-associated RCC is the
      commonest tumor subtype in ESRD, and biologically it appears to be more
      aggressive than the other tumor subtypes in ESRD.

PMID- 16434888
TI  - Sclerosing polycystic adenosis of the salivary gland: a report of 16 cases.
AB  - Sclerosing polycystic adenosis is a recently described, extremely rare, reactive,
      sclerosing, inflammatory process somewhat similar to fibrocystic changes and
      adenosis tumor of the breast. To date, there have been 22 cases described in the
      literature. Because of the infrequency of this lesion, we describe our combined
      experience with 16 cases, 1 of which has been previously reported. Thirteen
      tumors arose in the parotid gland, two involved the submandibular gland, and one
      arose in the buccal mucosa. There were 9 men and 7 women. Patients ranged in age
      from 9 to 75 years. Fourteen patients presented with a primary mass. Two were
      incidental findings in patients with a mixed tumor and an oncocytoma. Tumors
      ranged in size from 0.3 to 6 cm in greatest dimension. They are typically well
      circumscribed and are composed of densely sclerotic lobules with prominent cystic
      change. Hyperplasia of ductal and acinar elements and areas of apocrine-like
      metaplasia are frequent. Foci with mild ductal epithelial atypia were frequent
      with >50% of cases demonstrating at least focal areas of duct epithelial
      hyperplasia with atypia. Follow-up ranged from 1.5 to 40 years. One tumor
      recurred twice; no patient has developed metastases or died of disease.

PMID- 16434889
TI  - Prognostic significance of superficial fissuring ulceration in patients with
      severe "indeterminate" colitis.
AB  - Some colectomy specimens from patients with severe colitis contain superficial
      fissuring-type ulcers but do not have any other features of Crohn's disease (CD).
      This finding may cause difficulty with regard to distinguishing ulcerative
      colitis (UC) from CD and, thus, lead to a diagnosis of "indeterminate" colitis.
      The aim of this study was to evaluate the clinical and pathologic features, and
      outcome, of a cohort of patients with colitis and superficial fissuring ulcers,
      but without any other features that may suggest a diagnosis of CD. We
      retrospectively identified 21 patients (male-to-female ratio, 10/11; mean age, 38
      years) with severe chronic active colitis, all of whom had at least one (range, 1
      3) superficial fissuring ulcer in their colectomy specimens (but without any
      other features of CD), as well as a control group of 18 patients (male-to-female
      ratio, 10/8; mean age, 41 years) with equally severe disease, but without
      fissuring ulcers. Both groups were evaluated for a variety of clinical and
      pathologic features, such as clinical presentation, degree, extent, and duration
      of colitis, and follow-up information, such as the development of pouchitis,
      pouch fistulae, and any other features of CD. Overall, 81% of the study patients
      presented clinically with fulminant colitis and underwent an emergent or urgent
      colectomy, compared with only 41% of the control patients (P = 0.02). Nine (43%)
      study patients had active serositis in their colectomy specimens, whereas only 1
      (6%) control patient had this finding (P = 0.002). However, no significant
      differences were noted in either the extent or severity of disease or the
      presence of active ("backwash") ileitis, between the study and control groups.
      Upon follow-up (mean, 42 months; range, 4-121 months), the study patients with
      superficial fissuring ulcers developed pouchitis significantly more often (68%
      vs. 20%, P = 0.007) than the control group following an ileal pouch-anal
      anastomosis (IPAA) procedure. One patient from each group developed an anal
      fissure and another from each group developed an anastomotic stricture. In
      addition, 1 study patient developed a pouch-cutaneous fistula, and 1 control
      patient developed an enterocutaneous fistula to a loop ileostomy. Finally, 1
      control patient ultimately had her pouch excised because of recurrent intractable
      pouchitis. However, none of the other study or control patients developed any
      clinical or pathologic manifestations of CD. We conclude that superficial
      fissuring ulcers may occur in patients with severe chronic active UC,
      particularly those who present with fulminant disease. Affected individuals
      should not be considered to have CD or "indeterminate" colitis and should not be
      denied an IPAA procedure. Nevertheless, the presence of superficial fissuring
      type ulcers in patients with severe chronic active UC denotes a subgroup with a
      higher risk of pouchitis following surgical resection.

PMID- 16434890
TI  - Extracapsular lymph node involvement in node-positive patients with
      adenocarcinoma of the distal esophagus or gastroesophageal junction.
AB  - In adenocarcinoma of the esophagus or gastroesophageal junction, little attention
      has been paid to the biologic significance of extracapsular lymph node
      involvement (LNI). In the present study, a consecutive series of 251 patients
      with lymph node dissemination were reviewed. All patients underwent esophagectomy
      for adenocarcinoma and were prospectively followed. A total of 1562 positive
      lymph nodes were reexamined. Extracapsular LNI was identified in 456 lymph nodes
      (29%) in 166 patients (66%). Extracapsular LNI was confined to one lymph node in
      63 patients (38%). The occurrence of extracapsular LNI increased significantly
      with the depth of invasion, presence of positive resectable truncal nodes, number
      of resected nodes, number of positive nodes, and lymph node ratio. The median
      potential follow-up period was 58 months (range, 12-143 months). In this period,
      178 patients died of recurrent disease. The pattern of recurrence was comparable
      between patients with and without extracapsular LNI (P = 0.938). The median
      survival in patients with extracapsular LNI was 15 months (95% confidence
      interval, 12-18 months) compared with 41 months (95% confidence interval, 19-64
      months) in those without extracapsular LNI (P < 0.001). Median survival of
      patients with 2 or more lymph nodes was 12 months (95% confidence interval, 8-15
      months). Multivariate analysis demonstrated that T-stage, extracapsular LNI, and
      lymph node ratio were independent prognostic factors. The presence of
      extracapsular LNI identifies a subgroup with a significantly worse long-term
      survival. Together with the T-stage and the lymph node ratio, extracapsular LNI
      reflects a particularly aggressive biologic behavior and has significant
      prognostic potential.

PMID- 16434891
TI  - Ovarian involvement by metastatic colorectal adenocarcinoma: still a diagnostic
      challenge.
AB  - Ovarian involvement by metastatic colorectal adenocarcinoma, although not an
      uncommon occurrence, remains a diagnostic challenge. The gross and histologic
      features of such metastases overlap those of primary ovarian epithelial neoplasms
      such as endometrioid or mucinous adenocarcinoma. The clinical and pathologic
      features of 86 cases of metastatic colorectal adenocarcinoma involving the ovary
      were reviewed. Patients ranged in age from 19 to 85 years (median, 51 years); 24%
      were younger than 40 years. Presenting symptoms included abdominal or pelvic pain
      (45 cases), rectal bleeding (13 cases), change in bowel habits (20 cases), and
      vaginal bleeding (5 cases). In 23 cases, an ovarian mass was the first
      manifestation of the disease. Ovarian involvement was bilateral in 49 cases and
      unilateral in 33 (including 20 cases in which the only involved ovary measured at
      least 10 cm in greatest dimension). Involved ovaries ranged from 2 to 24 cm
      (mean, 10.1 cm), and most featured both solid and cystic areas. Many involved
      ovaries featured smooth capsules without gross evidence of surface involvement by
      tumor. In general, the tumors had typical histologic features of metastatic
      colorectal adenocarcinoma, including a garland pattern and dirty necrosis. In 23
      cases, foci with a benign or low malignant potential appearance were seen.
      Immunohistochemical studies showed that 29 of 29 tumors (100%) were positive for
      CK20; focal CK7 positivity was seen in 5 of 30 cases (17%). In 9 of the cases, an
      ovarian primary was diagnosed or favored initially, and 5 of these cases were
      initially treated as ovarian primaries. Metastatic colorectal adenocarcinoma
      should be considered in the differential diagnosis of an ovarian mass, even if
      the mass is large and unilateral or in a young patient, to secure proper
      treatment of these patients.

PMID- 16434892
TI  - Dysadherin expression in head and neck squamous cell carcinoma: association with
      lymphangiogenesis and prognostic significance.
AB  - Dysadherin is a recently characterized cancer-associated cell membrane
      glycoprotein that has a crucial role to cell-cell adhesiveness. The aim of this
      study was to examine dysadherin expression in head and neck squamous cell
      carcinoma (HNSCC). A total of 108 tissue specimens of patients with HNSCC were
      examined using immunostaining for dysadherin, E-cadherin, and the specific
      lymphatic endothelium marker D2-40. We quantified dysadherin and E-cadherin
      expression, assessed intratumoral (ILD) and peritumoral lymphatic density (PLD),
      and examined the possible associations of all the above parameters with
      clinicopathologic features and outcome. Finally, we used double staining with
      dysadherin and D2-40 to examine the expression pattern of dysadherin
      simultaneously with the lymphovasculature environment of HNSCC. High dysadherin
      expression was correlated with higher clinical stage (chi2, P = 0.01), with the
      presence of lymph node metastasis at the time of diagnosis (chi2, P = 0.02), and
      with increased ILD (chi2, P = 0.001). We observed an impressive reverse
      association between increased dysadherin expression and decreased E-cadherin
      expression (chi2, P < 0.001). Surprisingly, dysadherin-positive cancer cells
      usually gathered around areas of high intratumoral lymphatic vessel
      concentration, surrounding and invading small intratumoral lymphatics. Higher
      clinical stage and increased dysadherin expression were found to be the only
      significant independent prognostic factors for overall survival (hazard ratio,
      3.94; 95% confidence interval, 1.09-14.27 for clinical stage; hazard ratio, 3.92;
      95% confidence interval, 1.46-10.51 for dysadherin). The loss of intercellular
      adhesiveness and increased dysadherin expression seems to be related to
      lymphangiogenesis in HNSCC, but this should be confirmed by additional studies.
      Dysadherin expression might be a promising prognostic marker for separation of
      patients at higher risk.

PMID- 16434893
TI  - Lipid-rich variant of pancreatic endocrine neoplasms.
AB  - Most pancreatic endocrine neoplasms (PENs) show characteristic and well
      recognized endocrine morphology; however, a lipid-rich pattern, which can present
      a diagnostic problem in biopsies, has been reported, mostly as individual cases.
      Some have been included in descriptions of the rare clear-cell variant associated
      with von Hippel-Lindau (VHL) syndrome. The histogenesis, clinicopathologic
      characteristics, and significance of this lipid-rich pattern have not been
      unraveled. In this study, 11 PENs exhibiting foamy, microvesicular cytoplasm were
      analyzed. In some cases, the nuclei were distorted by the vesicles, and the usual
      endocrine chromatin pattern was not evident. The growth pattern was relatively
      diffuse, with vague compartmentalization of the cells by a delicate vasculature;
      prominent nesting was noted in only 4 cases. Pathology reports indicated
      substantial diagnostic challenge in these cases; on biopsies, 1 case was
      originally diagnosed as adrenal cortical carcinoma, another as renal cell
      carcinoma, a third as solid-pseudopapillary tumor, and a fourth had a fine needle
      aspiration cytologic diagnosis of adenocarcinoma. All cases were chromogranin and
      synaptophysin positive. Electron microscopy in 3 cases confirmed the cytoplasmic
      vesicles to be lipid vacuoles. Neurosecretory granules were also evident.
      Clinically, as in conventional PENs, there appeared to be two distinct subsets:
      Two cases were familial or functional/syndromic (1 with VHL and the other with
      MEN-1 and glucagonoma syndrome) and occurred in younger adults (ages 41 and 47
      years); the majority (n = 9) were nonfunctional/nonsyndromic and nonfamilial. The
      latter group was mostly represented by elderly males (mean age: 65 vs. 58 years
      in conventional sporadic PENs). Immunohistochemically, markers implicated in VHL
      associated neoplasia, including HIF-1alpha, inhibin, and Melan-A (in clear-cell
      PENs) and MUC6 (in serous cystadenomas) were mostly negative in lipid-rich PENs
      (1 of 10, 1 of 10, 0 of 10 and 0 of 10, respectively). In conclusion, the lipid
      rich pattern, reminiscent of adrenal cortical cells, represents a distinct subset
      of PENs. It presents a diagnostic challenge for surgical pathologists, especially
      in biopsies. EM supports the name lipid-rich for this variant. The findings
      suggest that the pathogenesis of lipid-rich tumors may be different from the VHL
      associated clear-cell variants of PENs.

PMID- 16434894
TI  - Chronic hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is traditionally divided on clinical grounds
      into acute, subacute, and chronic stages. Most biopsy specimens come from
      patients in the subacute stage, in which there is a relatively mild, usually
      peribronchiolar, chronic interstitial inflammatory infiltrate, accompanied in
      most cases by poorly formed interstitial granulomas or isolated giant cells.
      However, the pathologic features in the chronic, ie, fibrotic stage, are poorly
      defined in the literature. These features are important to recognize because the
      chronic stage of HP is often associated with a poor prognosis. We reviewed 13
      cases of chronic HP. Where information was available, exposures to the
      sensitizing agent had generally occurred over a long period of time. Three
      patterns of fibrosis were seen: 1) predominantly peripheral fibrosis in a patchy
      pattern with architectural distortion and fibroblast foci resembling,
      microscopically, usual interstitial pneumonia (UIP); 2) relatively homogeneous
      linear fibrosis resembling fibrotic nonspecific interstitial pneumonia (NSIP);
      and 3) irregular predominantly peribronchiolar fibrosis. In some instances,
      mixtures of the UIP-like and peribronchiolar patterns were found. In all cases,
      the presence of scattered poorly formed granulomas, or isolated interstitial
      giant cells, or sometimes only Schaumann bodies indicated the correct diagnosis.
      In 7 cases, areas of typical subacute HP were present as well. High-resolution CT
      scans showed variable patterns ranging from severe fibrosis, in some instances
      with an upper zone predominance, to predominantly ground glass opacities with
      peripheral reticulation. We conclude that, at the level of morphology, chronic HP
      may closely mimic UIP or fibrotic NSIP. If no areas of subacute HP are evident,
      the presence of isolated giant cells, poorly formed granulomas, or Schaumann
      bodies is crucial to arriving at the correct diagnosis, and the finding of
      peribronchiolar fibrosis may be helpful. Despite the presence of extensive
      fibrosis, some patients responded to removal from exposure and steroid therapy.

PMID- 16434895
TI  - Ectopic prostatic tissue in the uterine cervix and vagina: report of a series
      with a detailed immunohistochemical analysis.
AB  - Prostatic tissue has rarely been described in the lower female genital tract. We
      describe 6 cases of ectopic prostatic tissue: 5 involving the cervix and 1 the
      vagina. The latter is the first reported example of benign prostatic tissue in
      the vagina. The age of the patients ranged from 21 to 65 years; and in all cases,
      the prostatic tissue was located within the cervical or vaginal stroma without
      involvement of the surface. In all cases, there were both glandular and squamous
      elements, which varied in prominence. In some cases, the squamous elements
      predominated to such an extent that the underlying glandular component was easily
      overlooked. In the glandular areas, a double cell layer of luminal and basal
      cells was focally apparent. There was little cytologic atypia or mitotic
      activity. Immunohistochemically, 3 of 6 cases were positive with prostate
      specific antigen (PSA) and all 6 cases marked with prostatic acid phosphatase
      (PSAP). In some of the positive cases, staining was focal. Positive staining with
      prostatic markers was confined to the glandular elements with no staining of the
      squamous areas. Immunohistochemical staining with the high molecular weight
      cytokeratin 34betaE12 highlighted the basal cell layer, which often extended into
      the center of the cellular islands, reminiscent of basal cell hyperplasia
      involving the prostate gland. All cases tested were CD10 positive (largely
      restricted to the basal cell layer), alpha-methylacyl-CoA racemase positive, and
      p16 negative. Estrogen receptor (ER) and progesterone receptor (PR) were negative
      in the glandular areas, but ER was positive in the squamous elements in all cases
      and PR was positive in 1 case. All cases tested were androgen receptor positive
      and exhibited a low MIB-1 proliferation index with only scattered positive
      nuclei. The presence of ectopic prostatic tissue in the lower female genital
      tract may be more common than is appreciated. Once the possibility is considered,
      the diagnosis is easily confirmed using immunohistochemistry, although staining
      with prostatic markers may be focal and PSA may be negative. Ectopic prostatic
      tissue in the lower female genital tract is almost certainly a benign condition,
      based on the morphology, including the presence of a double cell layer, although
      follow-up of larger numbers of cases is required. Possible theories of
      histogenesis include a developmental anomaly, metaplasia of preexisting
      endocervical glands, and derivation from mesonephric remnants.

PMID- 16434896
TI  - Correlation between genetic alterations and microscopic features, clinical
      manifestations, and prognostic characteristics of thyroid papillary carcinomas.
AB  - Papillary carcinoma is the most common type of thyroid malignancy. It has been
      recently shown that these tumors commonly have one of three genetic alterations:
      BRAF point mutations, RET/PTC rearrangements, or RAS point mutations. In this
      study, we analyze the relationship between these alterations and the microscopic
      features of papillary carcinomas, their clinical features, and prognostic
      characteristics. Ninety-seven papillary carcinomas were studied; in all cases,
      frozen tissue was available for nucleic acid extraction. Of 96 unselected cases,
      42% were positive for BRAF, 18% for RET/PTC, and 15% for RAS mutations.
      Morphologic features were evaluated in detail in 61 cases and 6 characteristic
      nuclear features and 3 additional microscopic features were assessed
      quantitatively. At least 4 nuclear features were found in each tumor, with
      nuclear pseudoinclusions being the least frequent finding in all mutation groups.
      BRAF mutations were associated with older patient age, typical papillary
      appearance or the tall cell variant, a higher rate of extrathyroidal extension,
      and more advanced tumor stage at presentation. RET/PTC rearrangements presented
      at younger age and had predominantly typical papillary histology, frequent
      psammoma bodies, and a high rate of lymph node metastases. Tumors with RAS
      mutations were exclusively the follicular variant of papillary carcinoma and
      correlated with significantly less prominent nuclear features and low rate of
      lymph node metastases. These findings demonstrate that BRAF, RET/PTC, and RAS
      mutations are associated with distinct microscopic, clinical, and biologic
      features of thyroid papillary carcinomas.

PMID- 16434897
TI  - ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's
      lymphoma: report of 10 cases.
AB  - Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) are recognized as
      biologically distinct entities. However, occasionally, these two entities may
      share some morphologic features responsible for diagnostic difficulties. In the
      last 10 years, we have collected 380 cases of ALK-positive ALCL of which 10 cases
      were originally diagnosed as nodular sclerosis classic HL (NSHL) on conventional
      histopathological examination. After immunostaining, these cases proved to be ALK
      positive ALCL mimicking HL (so-called Hodgkin-like ALCL). These cases account for
      2.6% of our cases of ALK-positive ALCL (10 of 380 cases). Median age was 11 years
      (3-92 years) with a female predominance (male/female ratio, 3:7).
      Characteristically, these lesions showed thick nodular fibrosing bands highly
      suggestive of NSHL. Neoplastic cells were scarce in 6 cases, whereas in the 4
      remaining cases, sheets of tumor cells were also present. A perivascular and a
      sinusoidal growth pattern was observed in various degrees in all cases. Few
      binucleated Reed-Sternberg-like cells were present in every case in a background
      of small lymphocytes. Inflammatory cells (ie, granulocytes, eosinophils, and
      histiocytes) were rare. Neoplastic cells were positive for CD30 (10 of 10 cases),
      ALK protein (10 of 10 cases), epithelial membrane antigen (EMA) (9 of 9 cases),
      CD43 (6 of 9 cases), and perforin (8 of 8 cases), but negative for CD15 (10 of 10
      cases), CD20 (10 of 10 cases), Pax5/BSAP (6 of 6 cases), and EBV (8 of 8 cases).
      In addition, in 7 cases, neoplastic cells were of T-phenotype, whereas the 3
      remaining cases were considered to be of null/undetermined phenotype. Although
      rare, Hodgkin-like ALCL may mimic NSHL, and it is advisable to include EMA in the
      first line panel and to ask for ALK staining in EMA-positive, CD15-negative
      lesions with morphologic features suggestive of NSHL.

PMID- 16434898
TI  - The tubal fimbria is a preferred site for early adenocarcinoma in women with
      familial ovarian cancer syndrome.
AB  - A proportion of adenocarcinomas in prophylactic adnexectomies (bilateral salpingo
      oophorectomies [BSOs]) from women with BRCA mutations (BRCA positive) occur in
      the fallopian tube. We analyzed a consecutive series of BSOs from BRCA-positive
      women following an index case of fimbrial serous carcinoma. To determine if the
      fimbria is a preferred site of origin, we followed a protocol for Sectioning and
      Extensively Examining the FIMbria (SEE-FIM). Immunostaining for p53 and Ki-67 was
      also performed. Thirteen BRCA-positive women (cases) and 13 women undergoing BSOs
      for other disorders (controls) were studied. Tubal carcinoma was detected in 4
      cases at the initial histologic evaluation and in no controls. A fifth carcinoma
      was discovered following further sectioning of the fimbriae. Three were BRCA2
      positive and two BRCA1 positive. Three were in the fimbria, one in both the
      fimbria and proximal tube, and one involved the ampulla. Four were serous
      carcinomas, four were confined to the tube, and three were noninvasive
      (intraepithelial). No ovarian carcinomas were identified. All tumors were Ki-67
      positive (>75% of cell nuclei), and excluding one endometrioid carcinoma, p53
      positive (>75% cell nuclei); p53 positivity in the absence of elevated Ki-67 did
      not correlate with morphologic neoplasia. The fimbria was the most common
      location for early serous carcinoma in this series of BRCA-positive women.
      Protocols that extensively examine the fimbria (SEE-FIM) will maximize the
      detection of early tubal epithelial carcinoma in patients at risk for ovarian
      cancer. Investigative strategies targeting the fimbriated end of the fallopian
      tube should further define its role in the pathogenesis of familial and sporadic
      ovarian serous carcinomas.

PMID- 16434899
TI  - Intraarticular nodular fasciitis--a rare lesion: clinicopathologic analysis of a
      series.
AB  - Nodular fasciitis is a benign myofibroblastic proliferation with a predilection
      for the subcutaneous tissues of the upper extremities, trunk, and head and neck
      of young adults. Nodular fasciitis is not generally recognized to arise within
      joints. In this study, the clinicopathologic and immunohistochemical features of
      10 cases of intraarticular nodular fasciitis are described. Six patients were
      female and 4 were male, with a median age of 33 years (range, 9-50 years).
      Lesional size ranged from 2 to 4 cm (median, 2.6 cm). Seven tumors arose in the
      knee, 2 in the hand, and 1 in the ankle. Most patients complained of joint pain;
      4 presented with a palpable mass. Only 1 patient reported antecedent trauma. The
      duration of symptoms prior to surgery ranged from 2 months to 1 year (median, 6
      months). The clinical differential diagnoses included giant cell tumor of tendon
      sheath, pigmented villonodular synovitis, synovial chondromatosis, inflammatory
      arthritis, and lymphoma. Grossly, the lesions were solid, nodular, rubbery, or
      firm masses. Histologically, all tumors were circumscribed but unencapsulated and
      showed typical features of nodular fasciitis, being composed of cytologically
      bland plump spindle cells arranged in short, intersecting bundles within a
      variably loose myxoid to collagenous stroma, containing extravasated red blood
      cells and scattered lymphocytes. Five lesions showed prominent stromal
      hyalinization, in 2 cases keloidal in appearance. In 4 cases, the tissue at the
      periphery of the lesion showed hemosiderin deposition. By immunohistochemistry,
      all tumors examined were positive for SMA, 1 was positive for desmin, and all
      were negative for caldesmon and S-100 protein; none showed nuclear staining for
      beta-catenin. Clinical follow-up information was available for 5 patients,
      ranging from 2 to 86 months. No lesion recurred. In summary, intraarticular
      nodular fasciitis occurs most commonly in the knees of young adults, and often
      appears to have a somewhat longer preoperative duration than typical subcutaneous
      or intramuscular nodular fasciitis. Intraarticular lesions show morphologic
      features similar to other cases of nodular fasciitis, with the exception that
      stromal hyalinization and adjacent hemosiderin deposition are common, likely
      attributable to frictional trauma in this location.

PMID- 16434900
TI  - Increased rate of Helicobacter pylori infection detected by PCR in biopsies with
      chronic gastritis.
AB  - Histology is considered a sensitive method for detection of Helicobacter pylori,
      in gastric biopsies. We investigated the diagnostic potential of qualitative
      nested (nPCR) and quantitative PCR (qPCR) for detection of H. pylori using
      different primers on 126 archived gastric biopsies with inflammation and
      correlated the inflammatory changes with the presence and density of bacteria. H.
      pylori was detected in 42.8% biopsies by histology and PCR, an additional 15
      samples were positive exclusively by PCR: nPCR was positive in all histologically
      positive samples, but qPCR failed to detect H. pylori in 10 biopsies. The
      inflammatory score was significantly higher in biopsies positive for H. pylori
      only by PCR showed a significant higher inflammatory score compared with negative
      biopsies (mean of neutrophils score, 1.60 vs. 0.90, P < 0.01; mean of mononuclear
      cells score, 2.27 vs. 1.67, P < 0.01), whereas the inflammatory score was similar
      compared with biopsies positive for H. pylori by histology (mean of neutrophils
      score, 1.60 vs. 1.56, not significant; mean of mononuclear cells score, 2.27 vs.
      2.20, not significant). A weak correlation between inflammatory score and the
      density of H. pylori detected by histology was observed. The mean values of H.
      pylori DNA were significantly higher in histologic-positive than in histologic
      negative biopsies. We have shown that PCR can detect H. pylori in about 20% of
      histologic-negative gastric biopsies, indicating the clinical relevance of H.
      pylori detection by PCR in biopsies with characteristic inflammatory changes.

PMID- 16434901
TI  - Increased occurrence of caspase-dependent apoptosis in unfavorable
      neuroblastomas.
AB  - Neuroblastoma frequently shows spontaneous regression in which two distinct types
      of programmed cell death, ie, caspase-dependent apoptosis and H-Ras-mediated
      autophagic degeneration, have been suggested to play a key role. The current
      study was conducted to determine which of these cell suicide pathways
      predominated in this tumor regression. Periodic acid-Schiff (PAS) staining and
      immunostaining for H-Ras and for the full-length and cleaved forms of caspase-3,
      poly (ADP-ribose) polymerase (PARP), and lamin A were carried out on 55 archival
      tumor specimens. The incidence of caspase-dependent apoptosis in each tumor was
      quantified by cleaved lamin A staining and compared with clinicopathologic
      prognostic factors. Although a recent report has shown that neuroblastic cells
      undergoing autophagic degeneration were readily detectable by PAS and H-Ras
      staining, we could not confirm this result in any of our samples with the
      exception of one tumor. Instead, many of our neuroblastoma samples showed
      nonspecific PAS and Ras staining in areas of necrosis, suggesting that autophagic
      "degeneration" indeed corresponds to coagulation necrosis or oncosis.
      Unexpectedly, the incidence of caspase-dependent apoptosis was significantly
      correlated with indicators of a poor prognosis in these tumors, including
      Shimada's unfavorable histology, MYCN amplification, and a higher mitosis
      karyorrhexis index, but not with factors related to tumor regression such as
      clinical stage and mass screening. These results indicate that neither caspase
      dependent apoptosis nor autophagic "degeneration" may be involved in spontaneous
      neuroblastoma regression. This suggests that other mechanisms, perhaps such as
      tumor maturation, may be responsible for this phenomenon.

PMID- 16434902
TI  - Pneumopolycystic endometritis.
AB  - Emphysematous inflammations of the abdomen and pelvis are uncommon and
      potentially life-threatening conditions that require aggressive treatment.
      Pneumopolycystic endometritis is a rare benign condition of which only 1 case has
      been described. This report describes the sonographic and histologic appearance
      of pneumopolycystic endometritis in a 49-year-old woman who presented with
      irregular menses and hypermenorrhea of 1 year's duration. The entity is
      characterized by gas-filled cysts in the endometrium stroma, in a pattern similar
      to pneumatosis of the vagina. The histologic picture is specific and should not
      be confused with gas gangrene involving the uterus characterized by the presence
      of tissue necrosis and life-threatening infection. Our patient is the first
      documented case that occurred spontaneously and at the same time was limited to
      the endometrium. Recognition of pneumopolycystic endometritis is important
      because this condition does not represent an aggressive life-threatening
      infection, and spontaneous resolution is to be expected.

PMID- 16434903
TI  - Pulmonary extranodal marginal zone lymphoma with massive crystal storing
      histiocytosis.
AB  - We present an incidentally discovered, unusual case of pulmonary bronchial mucosa
      associated lymphoid tissue lymphoma associated with massive crystal storing
      histiocytosis in a 69-year-old woman. The neoplastic process was masked by large
      numbers of epithelioid and spindled histiocytes containing crystalline material.
      Histochemical stains showed intracytoplasmic crystals and immunoperoxidase
      staining confirmed the histiocytic nature of the swollen cells. Electron
      microscopy demonstrated the characteristic appearance of immunoglobulin crystals.
      Lymphoepithelial lesions were identified on immunohistochemical staining,
      compounding suspicions of an underlying lymphoid neoplasm. Molecular studies
      later revealed a monoclonal B-cell population. The patient had no systemic
      evidence of a paraproteinemia. Crystal storing histiocytosis is a rare phenomenon
      in which macrophages accumulate light chain or immunoglobulin crystalline
      inclusions. The disease may be systemic, or localized as in this case. It is
      usually associated with the excess production of a monoclonal immunoglobulin,
      although there have been many case reports without this feature. An overview of
      crystal storing histiocytosis is given.

PMID- 16434904
TI  - Sustentaculoma: report of a case of a distinctive neoplasm of the adrenal
      medulla.
AB  - A case of a morphologically distinctive tumor of the adrenal medulla occurring in
      a 54-year-old woman is described. On microscopic examination, the tumor was well
      circumscribed and characterized by the presence of ill-defined, irregular nests
      of spindle cells with oval to elongated nuclei, tiny nucleoli, and abundant
      eosinophilic cytoplasm. The tumor was associated with a moderate infiltrate of
      lymphocytes and plasma cells with occasional lymphoid follicles. Necrosis, marked
      cellular atypia, and mitoses were absent. Immunohistochemical studies
      demonstrated the tumor cells to be strongly reactive for vimentin, S-100 protein,
      and CD56, and nonreactive for glial fibrillary acidic protein, chromogranin,
      synaptophysin, melanoma-associated antigens, and dendritic cell markers.
      Ultrastructural examination showed elongated cells with interdigitating
      cytoplasmic processes devoid of a basal lamina. No secretory granules were noted.
      The morphology, immunophenotype, and ultrastructure of this unique neoplasm
      suggest derivation from sustentacular cells of the adrenal medulla. We propose
      the designation "sustentaculoma" for this hitherto undescribed neoplasm of the
      adrenal gland.

PMID- 16434905
TI  - Confirmation of diagnosis of cat scratch disease by immunohistochemistry.

PMID- 16434906
TI  - CD34 expression in mesothelial/monocytic cardiac excrescence.

PMID- 16434907
TI  - Racial and ethnic differences in receipt and use of health information in
      encounters between patients and physicians.

PMID- 16434908
TI  - Self-advocacy during the medical encounter: use of health information and
      racial/ethnic differences.
AB  - BACKGROUND: Research indicates that patients who self-advocate during the medical
      encounter gain maximum benefit. However, little is known about racial/ethnic
      differences in self-advocacy. OBJECTIVE: We sought to examine whether
      race/ethnicity and obtaining health information are associated with self-advocacy
      (mentioned health information to physician and physician ordered tests based on
      health information). METHODS: Study data were drawn from the 2000-2001 Household
      Component of the Community Tracking Study, a nationally representative survey.
      The study sample included 7419 women ages 45 to 64 who had at least 1 physician
      visit in the previous year. Binomial logit models were used to assess self
      advocacy. Probability adjustments were applied to results. RESULTS: In the full
      sample (n = 7419), women who obtained health information were almost 5 times more
      likely to mention that information to their physician (odds ration [OR] = 4.76,
      95% confidence interval [CI] 4.05-5.60) than women who did not obtain
      information. Black women were less likely to mention health information to their
      physician (OR = 0.52, 95% CI = 0.37-0.73) than white women. Among women who
      obtained health information (n = 3690), black women also were less likely to
      mention health information to their physician (OR = 0.57, 95% CI = 0.40-0.83)
      than white women. Among those who mentioned health information to the physician,
      Hispanic women were more likely than white women to have a
      test/procedure/prescription prescribed (OR = 2.15, 95% CI = 1.10-4.20). However,
      after adjusting probability, this difference was not statistically significant.
      CONCLUSIONS: Although health information was associated with self-advocacy, black
      women were less likely to self-advocate. Further research is needed to better
      understand factors that impede black women from self-advocating.

PMID- 16434909
TI  - Unforeseen inpatient mortality among veterans with schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have co-occurring medical conditions,
      like other patients, but may lack the capacity to provide good self-care or to
      work with their providers to ensure appropriate medical treatment. We
      hypothesized that death among patients with schizophrenia occurs more frequently
      after minimal care of comorbid conditions. METHODS: All patients who died in
      veterans affairs (VA) hospitals during FY02 were categorized as to type of death:
      unforeseen (age <80 years, 1-2 inpatient days past year), cancer, organ failure
      (heart, lungs, kidneys), frailty (dementias, hip fractures, dehydration, etc.),
      or other deaths. Logistic regression explored factors in unforeseen death.
      RESULTS: During the year, 27,798 patients died in VA facilities; 3% had
      schizophrenia (n = 943). Roughly two-thirds of all deaths were from cancer or
      organ failure, 11% frailty, 9% other, and 8% met criteria for unforeseen death.
      Among patients with schizophrenia, however, 20% fell into the unforeseen death
      category. In an adjusted model, schizophrenia was associated with a 2-fold
      increased risk of unforeseen death compared with any other category (odds ratio =
      2.4, 95% confidence interval 1.6-3.4). Unforeseen death was less likely among
      patients with substance abuse diagnoses in the year before death and more likely
      when patients had no outpatient medical care. CONCLUSIONS: VA patients with
      schizophrenia were more likely to die as inpatients with little previous-year
      care compared with other inpatient decedents without schizophrenia. Outreach
      efforts may be necessary to engage patients with schizophrenia in treatment of
      potentially life-threatening conditions.

PMID- 16434910
TI  - Readiness to report medical treatment errors: the effects of safety procedures,
      safety information, and priority of safety.
AB  - BACKGROUND: Medical error reporting is an essential component of patient safety
      enhancement. However, increasingly, the literature points to a problem of
      underreporting of treatment errors, mainly as a result of the fear of malpractice
      lawsuits and limited formal data collection systems. Few studies, if any, have
      examined the influence of informal aspects of the organization, such as safety
      climate, on employees' willingness to report errors. OBJECTIVES: This study
      investigated the relationship between safety climate aspects and personnel
      readiness to report treatment errors in different hospital departments. METHOD:
      The model was tested in 3 hospitals (n = 632 in 44 medical departments of 3
      types; internal medicine, surgery, and intensive care). Three safety climate
      aspects were measured using questionnaires: the way employees perceive the safety
      procedures, the safety information flow within their department, and the relative
      priorities given to safety in the department. Readiness to report was measured by
      tallying each department's annual number of treatment errors reported to the
      hospitals' risk management systems. RESULTS: Negative binomial regression
      analysis indicated that the more personnel perceive procedures as suitable and
      safety information as available, the higher was their willingness to report
      treatment errors. These relationships significantly differed depending on the
      department type. CONCLUSIONS: Hospitals should take into account the perceptions
      of personnel regarding safety procedures and information and understand that
      these perceptions operate differently in different department types in their
      effect on the staff's willingness to report treatment errors.

PMID- 16434912
TI  - What is the concordance between the medical record and patient self-report as
      data sources for ambulatory care?
AB  - BACKGROUND: The validity of quality of care assessments relies upon data quality,
      yet little is known about the relative completeness and validity of data sources
      for evaluating the quality of care. OBJECTIVES: We evaluated concordance between
      ambulatory medical record and patient survey data. Levels of concordance,
      variations by type of item, sources of disagreement between data sources, and
      implications for quality of care assessment efforts are discussed. DESIGN AND
      SUBJECTS: This was an observational study that included 1270 patients sampled
      from 39 West Coast medical organizations with at least 1 of the following:
      diabetes, ischemic heart disease, asthma or chronic obstructive pulmonary
      disease, or low back pain. MEASURES: Items from both data sources were grouped
      into 4 conceptual domains: diagnosis, clinical services delivered, counseling and
      referral, and medication use. We present total agreement, kappa, sensitivity, and
      specificity at the item and domain-levels and for all items combined. RESULTS: We
      found good concordance between survey and medical records overall, but there was
      substantial variation within and across domains. The worst concordance was in the
      counseling and referrals domain, the best in the medication use domain. Patients
      were able to report with good sensitivity on memorable items. CONCLUSIONS:
      Quality ratings are likely to vary in differing directions, depending on the data
      source used. The most appropriate data source for analyses of components of and
      overall quality of care must be considered in light of study objectives and
      resources. We recommend data collection from multiple sources to most accurately
      portray the patient and provider experience of medical care.

PMID- 16434911
TI  - External validation of medicare claims for breast cancer chemotherapy compared
      with medical chart reviews.
AB  - BACKGROUND: Although Medicare claims data have been increasingly used to examine
      the patterns and outcomes of cancer chemotherapy, their external validity has not
      been well studied. OBJECTIVES: We sought to validate Medicare claims for
      chemotherapy compared with medical chart reviews. PATIENTS AND METHODS: We
      completed medical chart reviews for 1228 women who were diagnosed with breast
      cancer at age 65 and older between 1993 and 1999 in New Mexico that were linked
      with Medicare claims data, achieving an estimated sensitivity of more than 90%
      and a 0.05 level of precision. RESULTS: Of the 150 subjects identified by
      Medicare claims as receiving chemotherapy within 6 months of diagnosis, 75% were
      confirmed by medical records as having received chemotherapy. Of the remaining
      25% of cases without chart verification, (1) 33 cases had 7 or more claims for
      chemotherapy and also had specific chemotherapy drugs indicated in Medicare data,
      representing 22% (33/150) of all cases that received chemotherapy according to
      Medicare claims and (2) 4 cases had 1 to 6 claims for chemotherapy, representing
      3% (4/150) of all cases with claims for chemotherapy. Of those 1078 subjects who
      did not receive chemotherapy according to Medicare claims, more than 99% were
      confirmed by chart reviews. Observed agreement on chemotherapy between Medicare
      claims and chart reviews was 94% and overall reliability (kappa) was 0.69 (95%
      confidence interval = 0.63-0.76). CONCLUSIONS: Of cases identified as receiving
      chemotherapy by Medicare claims, 97% had strong evidence and only 3% had weak
      evidence for receiving this therapy.

PMID- 16434913
TI  - Comparison of administrative data and medical records to measure the quality of
      medical care provided to vulnerable older patients.
AB  - BACKGROUND: Administrative data are used to determine performance for publicly
      reported in health plan "report cards," accreditation status, and reimbursement.
      However, it is unclear how performance based on administrative data and medical
      records compare. METHODS: We compared applicability, eligibility, and performance
      on 182 measures of health care quality using medical records and administrative
      data during a 13-month period for a random sample of 399 vulnerable older
      patients enrolled in managed care. RESULTS: Of 182 quality indicators (QIs)
      spanning 22 conditions, 145 (80%) were applicable only to medical records and 37
      (20%) to either medical records or administrative data. Among 48 QIs specific to
      geriatric conditions, all were applicable to medical records; 2 of these also
      were applicable to administrative data. Eligibility for the 37 QIs that were
      applicable to both medical records and administrative data was similar for both
      data sources (94% agreement, kappa = 0.74). With the use of medical records, 152
      of the 182 the QIs that were applicable to medical records were triggered and
      yielded an overall performance of 55%. Using administrative data, 30 of the 37
      QIs that were applicable to administrative data were triggered and yielded
      overall performance of 83% (P < 0.05 vs. medical records). Restricting to QIs
      applicable to both data sources, overall performance was 84% and 83% (P = 0.21)
      for medical records and administrative data, respectively. CONCLUSIONS: The
      number and spectrum of QIs that can be measured for vulnerable elderly patients
      is far greater for medical records than for administrative data. Although summary
      estimates of health care quality derived from administrative data and medical
      records do not differ when using identical measures, summary scores from these
      data sources vary substantially when the totality of care that can be measured by
      each data source is measured.

PMID- 16434914
TI  - Development and validation of an index to predict activity of daily living
      dependence in community-dwelling elders.
AB  - BACKGROUND: Maintaining independence in daily functioning is an important health
      outcome in older adults. A key measure of functional independence in elders is
      the ability to do activities of daily living (ADL) without the assistance of
      another person. However, few prognostic indices have been developed that stratify
      elders into groups at variable risk for developing ADL dependence. OBJECTIVE: We
      sought to develop and validate a prognostic index that distinguishes between
      elders at different risk of ADL dependence. RESEARCH DESIGN, SUBJECTS, AND
      MEASURES: We studied subjects enrolled in Asset and Health Dynamics Among the
      Oldest Old (AHEAD), a nationally representative cohort of elders older than the
      age of 70. We included 5239 subjects (mean age, 77) reporting that they could do
      each of 5 ADL (bathing, dressing, toileting, transferring, and eating) without
      the assistance of another person at baseline. Subjects were divided into
      development (n = 3245) and validation (n = 1994) samples based on region of the
      United States. Our primary outcome was the need for help (dependence) with at
      least one ADL at 2 years. We used logistic regression to select among predictor
      variables encompassing several domains: demographic characteristics, comorbid
      conditions, functional status, cognitive status, and general health indicators.
      RESULTS: The 9 independent predictors of 2-year ADL dependence were age older
      than 80, diabetes, difficulty walking several blocks, difficulty bathing or
      dressing, need for help with personal finances, difficulty lifting 10 pounds,
      inability to name the Vice President, history of falling, and low body mass
      index. We created a risk score by assigning 1 point to each risk factor. In the
      development sample, rates of 2-year ADL dependence in subjects with 0, 1, 2, 3,
      4, and 5 or more risk factors were 1.3%, 2.8%, 3.8%, 10%, 22%, and 33%,
      respectively (P < 0.001, roc area = 0.79). In the validation sample, the rates
      were 0.7%, 4.3%, 8.7%, 11%, 18%, and 40% (P < 0.001, roc area = 0.77). The risk
      score also discriminated between subjects at variable risk for a combined outcome
      of either ADL decline or death (4.3%, 7.6%, 15%, 21%, 30%, and 47%). CONCLUSION:
      Using data available from patient reports, we validated a simple risk index that
      distinguished between elders at variable risk of ADL dependence. This index may
      be useful for identifying elders at high risk of poor outcomes or for risk
      adjustment.

PMID- 16434916
TI  - Evaluating patients' experiences with individual physicians: a randomized trial
      of mail, internet, and interactive voice response telephone administration of
      surveys.
AB  - BACKGROUND: There is increasing interest in measuring patients' experiences with
      individual physicians, and empirical evidence supports this area of measurement.
      However, the high cost of data collection remains a significant barrier. Survey
      modes with the potential to lower costs, such as Internet and interactive voice
      response (IVR) telephone, are attractive alternatives to mail, but their
      comparative response rates and data quality have not been tested. METHODS: We
      randomly assigned adult patients from the panels of 62 primary care physicians in
      California to complete a brief, validated patient questionnaire by mail, Internet
      (web), or IVR. After 2 invitations, web and IVR nonrespondents were mailed a
      paper copy of the survey ("crossover" to mail). We analyzed and compared (n =
      9126) the response rates, respondent characteristics, substantive responses, and
      costs by mode (mail, web and IVR) and evaluated the impact of "crossover"
      respondents. RESULTS: Response rates were higher by mail (50.8%) than web (18.4%)
      or IVR (34.7%), but after crossover mailings, response rates in each arm were
      approximately 50%. Mail and web produced identical scores for individual
      physicians, but IVR scores were significantly lower even after adjusting for
      respondent characteristics. There were no significant physician-mode
      interactions, indicating that statistical adjustment for mode resolves the IVR
      effect. Web and IVR costs were higher than mail. CONCLUSIONS: The equivalence of
      individual physician results in mail and web modes is noteworthy, as is evidence
      that IVR results are comparable after adjustment for mode. However, the higher
      overall cost of web and IVR, as the result of the need for mailings to support
      these modes, suggests that they do not presently solve cost concerns related to
      obtaining physician-specific information from patients.

PMID- 16434915
TI  - Health values of patients coinfected with HIV/hepatitis C: are two viruses worse
      than one?
AB  - OBJECTIVES: We sought to assess health values of patients coinfected with
      HIV/hepatitis C (HCV) and compare them with those of patients singly infected
      with HIV or HCV and to characterize and assess the relationship of clinical and
      nonhealth-related factors with health values. SUBJECTS: We studied a total of 203
      subjects infected with HIV, HCV, or both. MEASURES: We assessed rating scale
      (RS), time tradeoff (TTO), and standard gamble (SG) values, and we explored
      associations of health values with the Mental Component Summary (MCS) and
      Physical Component Summary (PCS) of the SF-12; number of bothersome symptoms from
      the HIV Symptoms Index; spirituality, as assessed by the Functional Assessment of
      Chronic Illness Therapy, Spiritual Well-being scale; as well as with a number of
      demographic, clinical, and psychosocial characteristics. RESULTS: Of the 203
      subjects, 59 (29%) had HIV monoinfection, 69 (34%) had HCV monoinfection, and 75
      (37%) were coinfected. The mean (SD) health values for the cohort were: RS = 0.69
      (0.23), TTO= 0.88 (0.24), and SG = 0.78 (0.30). Infection type was related,
      albeit differently, to TTO values (mean values for patients with coinfection =
      0.82; HIV = 0.91; and HCV = 0.91 [P < 0.05]) and SG values (coinfection = 0.77;
      HIV = 0.70; and HCV = 0.87; P < 0.05). In multivariable models, RS scores were
      significantly associated with sexual orientation, PCS scores, MCS scores,
      symptoms, and spirituality (adjusted R = 0.61); TTO with symptoms and
      spirituality (adjusted R = 0.23); and SG with infection type, PCS scores, and
      symptoms (adjusted R = 0.24). CONCLUSIONS: Health values and their correlates
      varied by method of assessment. Health values appear to be driven more by
      symptoms, health status, and spirituality than by number of viral infections.

PMID- 16434917
TI  - Case-finding for depression among medical outpatients in the Veterans Health
      Administration.
AB  - OBJECTIVES: We sought to determine the rates and predictors of screening,
      screening positive, follow-up evaluation, and subsequent diagnosis of depression
      among medical outpatients. RESEARCH DESIGN: This was a cross-sectional study
      using chart-review data from the Department of Veterans Affairs (VA) 2002
      External Peer Review Program merged with administrative data. SUBJECTS AND
      MEASURES: We studied a national sample of VA medical outpatients with no
      depression diagnosis or mental health visits in the past 6 months (n = 21,489)
      and used chart-review and administrative data to follow the chain of events from
      depression screening to diagnosis. RESULTS: Overall, 84.9% of eligible patients
      (n = 18,245) were screened for depression in the past year. Of the 8.8% who
      screened positive, only 54.0% received follow-up evaluation and, of these, 23.6%
      (n = 204) subsequently were diagnosed with a depressive disorder (representing
      1.1% of the originally screened sample). Patients who were younger, unmarried,
      and had more medical comorbidities were less likely to be screened; however, if
      screened, they were more likely to screen positive. Male gender and greater
      medical comorbidity were associated with decreased odds of follow-up evaluation
      after a positive screen. At the facility level, likelihood of depression
      screening was inversely associated with spending on teaching and research but
      positively associated with spending on mental health care. CONCLUSIONS: VA's
      depression case-finding activities yielded relatively few positive cases, raising
      questions about cost-effectiveness. Targeted strategies may increase the value of
      case-finding among patients at greatest risk for depression and at more
      academically affiliated medical centers. Targeted efforts also are needed to
      ensure proper follow-up evaluation of suspected cases, particularly among male
      patients and those with increased medical comorbidity.

PMID- 16434918
TI  - Accidental iatrogenic pneumothorax in hospitalized patients.
AB  - OBJECTIVE: Iatrogenic pneumothorax (IP) is an inherent risk to patients who
      undergo procedures that involve the intentional puncturing of the lung. IP also
      could occur accidentally to patients who do not undergo such procedures; such
      accidental IP (AIP) is suggestive of lapses in safe care. This study assessed the
      risk for AIP in patients hospitalized with specific diagnoses who underwent
      specific procedures. RESEARCH DESIGN: We analyzed 7.5 million discharge abstracts
      from 994 short-term acute care hospitals across 28 states in 2000 in the Agency
      for Healthcare Research and Quality (AHRQ), Healthcare Cost and Utilization
      Project Nationwide Inpatient Sample. AHRQ Patient Safety Indicators (PSIs) were
      used to identify AIP. AIP incidences and associated diagnoses and procedures were
      explored. RESULTS: Patients who were admitted for pleurisy, cancer of the kidney
      and renal pelvis, or conduction disorders and complications of cardiac devices
      had the highest rates of developing AIP during hospitalization, with AIP rates at
      2.24%, 1.14%, and 0.83% respectively. The procedure-specific rates for AIP varied
      from 2.68% for patients who underwent thoracentesis to 1.30% for those who
      underwent nephrectomy, to 0.06% for those who underwent gastrostomy.
      Thoracentesis appeared to be a high-risk procedure for patients who were admitted
      for secondary malignancies, pleurisy, or pneumonia, with AIP rates at 3.76%,
      3.13%, and 2.28%, respectively. CONCLUSIONS: Although AIP is most common after
      thoracentesis, it is a substantial threat to patients undergoing a wide range of
      procedures.

PMID- 16434919
TI  - Psychological distress as a barrier to preventive care in community-dwelling
      elderly in the United States.
AB  - OBJECTIVE: The presence of psychologic distress in older adults may be associated
      with decreased adherence to recommended preventive-care services. This analysis
      aimed to measure the association between psychologic distress and adherence to
      United States Preventive Services Task Force (USPSTF)-recommended preventive-care
      services among older adults in the United States. DESIGN: We undertook a cross
      sectional analysis of 3655 U.S. community-dwelling elderly from the 2001 Medical
      Expenditure Panel (MEPS) survey. MEASUREMENTS: The presence of psychologic
      distress was captured by the Mental Component Survey (MCS) of the SF-12. The
      receipt of 9 preventive care services were captured using MEPS: hypertension
      screening, influenza vaccination, fecal occult blood testing or sigmoidoscopy,
      mammography, clinical breast examination, cholesterol screening, prostate
      specific antigen test, routine check-up, and dental checkup. RESULTS: Elderly
      reporting psychologic distress were 30% less likely than nondistressed elderly to
      receive influenza vaccination (OR = 0.70, 95% CI = 0.55-0.88) and 23% less likely
      to receive annual dental check-ups (OR= 0.77, 95% CI = 0.61-0.97). Women with
      psychologic distress were 27% less likely to receive a clinical breast
      examination (OR = 0.73, 95% CI = 0.57-0.94). Psychologic distress was not
      significantly associated with screening for hypertension, colon cancer, high
      cholesterol, or prostrate cancer, mammography, or routine check-ups. CONCLUSIONS:
      Elderly reporting psychologic distress were less likely to adhere to some, but
      not all, recommended preventive care guidelines. These results suggest that
      adherence to recommended preventive care guidelines may be improved, indirectly,
      by improving recognition and treatment of emotional health problems in the
      elderly.

PMID- 16434920
TI  - Perceived barriers to mental health service use among individuals with mental
      disorders in the Canadian general population.
AB  - BACKGROUND: Eliminating barriers to care is important for improving health
      service use. However, the barriers to mental health care have not been well
      investigated. OBJECTIVES: This study was designed to provide information about
      the barriers to mental health service use and to identify clinical factors
      associated with perceived barriers among individuals with depressive-, anxiety-,
      and substance use-related disorders in the communities. DESIGN: A cross-sectional
      analysis using data from the Canadian Community Health Survey-Mental Health and
      Well-being was instituted. SUBJECTS: Participants with depressive-, anxiety-, and
      substance use-related disorders in the past 12 months, assessed by the World
      Mental Health-Composite International Diagnostic Interview, were included (n =
      4094). RESULTS: In participants with mental disorders, 19.5% reported barriers to
      mental health service use. The percentage of perceived barriers due to
      acceptability was higher than those for barriers due to accessibility and
      availability. Participants with comorbid mental disorders were more likely to
      have experienced barriers than those with one disorder in both mental health
      service users and in the nonusers. Role impairment was a significant factor
      predicting barriers to care, overall and in the service nonusers, in the groups
      having anxiety disorders only, having any depressive or anxiety disorders, and
      having any alcohol or drug dependence. CONCLUSIONS: Clinical characteristics play
      an important role in perceiving barriers to mental health care. Future efforts
      should pay particular attention to the needs of those with chronic and severe
      mental health problems and focus on improving the effectiveness of mental health
      services.

PMID- 16434921
TI  - [Social responsibility of epidemiologists: a welcome debate].

PMID- 16434922
TI  - [Five-year survival of Ile-de-France cancer patients diagnosed in 1994].
AB  - BACKGROUND: This study aimed to estimate survival at 5 years by localization, sex
      and stage of the patients who presented a new cancer in 1994 in the Ile-de-France
      area. METHODS: A cohort study began in 1994 by an exhaustive collection of the
      incidental cancers notified in the Ile-de-France area at the health insurance
      (27,080 patients). A stratified random sample based on tumor localization was
      followed at 1 year, 3 years and 5 years. The analysis of the observed survival
      was carried out according to Kaplan-Meier method. Relative survival was
      calculated according to Ederer II method. RESULTS: The follow-up sample concerned
      4,166 patients. For all cancers, relative survival at 5 years was 65% for the
      women and 51% for the men. Relative survival rate at 5 years was 82% for the
      women with a breast cancer (98% for the patients in stage I) and 66% for those
      with a cancer of the cervix. Relative survival at 5 years for colonic cancer was
      67% for men and 54% for women. For lung cancer, the relative survival rate fell
      from 47% for patients in stage I to 5% for those in stage IV. CONCLUSION: Our
      study produces population-based survival data for a entire geographical area
      covering 20% of the French population. Survival improves with earlier diagnosis
      but depends also on quality of care and availability of care: access to medical
      care can be a favouring factor. While in terms of incidence the situation in the
      Ile-de-France area is close to the national situation, survival at 5 years for a
      set of tumors appears to be better in this area than the nationwide figures.
      Besides providing information useful to determine mortality and incidence, the
      health insurance data offer additional insight to cancer epidemiology and
      contribute to better knowledge of this disease.

PMID- 16434923
TI  - [Quantitative assessment of the risk of lung cancer and pleural mesothelioma
      among automobile mechanics].
AB  - BACKGROUND: A quantitative assessment of the risk of lung cancer and pleural
      mesothelioma among mechanics exposed to dust released from automobile asbestos
      containing parts was performed. METHODS: The population of automobile mechanics
      in France, according to profession and industrial sectors codes, was estimated
      from the data of the 1999 census. Risks were computed for a total male population
      of 242,360 automobile mechanics aged 16 to 60 years. Exposure to asbestos among
      these workers comes from maintenance tasks involving asbestos-containing parts
      produced before 1997 (date of the asbestos ban in France). Airborne asbestos
      concentration data available from the literature were highly variable. No data
      reporting the distribution of time spent for such tasks over a typical week of
      work were available. Therefore, different weekly exposure profiles were
      simulated, based on data from the 1994 SUMER survey. Risk models were those used
      for assessing asbestos health effects by all national and international agencies.
      Exposure scenarios mixed different levels of exposure, periods of time,
      proportions of exposed workers and dates of the "natural" disappearance of the
      automobile fleet built before asbestos was banned in brakes and other parts. The
      most realistic scenario hypothesizes that all automobile mechanics were exposed
      to asbestos, that the exposure levels ranged from 0.06 and 0.25 fibers/liter per
      week for the period before 1997, and between 0.01 and 0.06 fibers/liter per week
      afterwards until 2010. RESULTS: According to this scenario, the number of
      lifelong cancer deaths (lung and pleura) induced by asbestos exposure in this
      population is estimated at 602 "unavoidable" cases, due to exposure experienced
      before 2003; 43 other cases will occur if asbestos is not removed from existing
      automobiles.

PMID- 16434924
TI  - [Estimation of the epidemiological impact of various BCG vaccination scenarios in
      France].
AB  - BACKGROUND: Within the current process of revising the vaccination policy against
      tuberculosis in France, we have estimated the epidemiological impact of three
      future possible options for BCG primo-vaccination: continuation of routine
      vaccination of all children, targeting on high risk children or discontinuation.
      METHODS: We have used tuberculosis mandatory notification data to estimate the
      number of cases currently prevented each year through BCG vaccination,
      corresponding to the excess incidence, in case of discontinuation of the
      vaccination. The proportion of cases occurring in high risk children has been
      estimated through data from a study carried out in 1997 in the Paris region. The
      contribution of high risk children to the French child population has been
      estimated using data from INSEE and INED. RESULTS: In the most favorable scenario
      for vaccination, up to 800 additional cases would have occurred annually,
      considering all BCG vaccination activities in children were interrupted. The
      selective vaccination strategy would induce around 200 additional cases each year
      considering the coverage remained at its current level. Therefore the vaccination
      of less than 15% of each annual birth cohort would allow prevention of around
      three quarters of the cases currently occurring. CONCLUSION: BCG vaccination of
      high risk children seems to be an efficient strategy. However, its current
      effectiveness would depend on the capacity to maintain a high vaccination
      coverage in this population in the context of the abrogation of mandatory
      vaccination and the impending disappearance of BCG administered by multipuncture,
      which is the technique used in France for the vast majority of primo
      vaccinations. Beyond the economical and epidemiological parameters, the decision
      will have to consider the operational, social and ethical issues raised by a
      vaccination strategy targeting children mainly of foreign origin.

PMID- 16434925
TI  - [Demographic and socioeconomic factors associated with needs for home assistance
      among community-dwelling elderly: a study from the French Home Survey Handicaps
      Disabilities-Dependence].
AB  - BACKGROUND: Gains in life expectancy in western countries have mainly come hand
      in hand with growing chronic diseases and disabilities related to the activities
      of daily living (ADL) and instrumental activities of daily living (IADL).
      Although these disabilities have been identified as predictors of
      institutionalization, the elderly in France continue to live at home, in the
      community, alone or with others. This work aims at identifying and assessing
      their needs for assistance and looks especially at the demographic and
      socioeconomic associated features. METHODS: Reported needs for assistance with
      ADL and IADL are studied through a representative sample of 8,745 people aged 60
      years and older and living at home in 1999, taken from the French cross-sectional
      "Handicaps-Disabilities-Dependence" survey. Statistical associations (non
      adjusted and adjusted Odds-Ratio-OR) have been computed in a conceptual framework
      derived from Andersen and Newman's behavioural model. RESULTS: More than 1
      million people aged 60 years and older need assistance from another person to
      perform at least one ADL (bathing, dressing, going to toilet, eating,
      transferring, getting outside) and about 2.5 millions persons for at least one
      IADL (shopping, food preparation, housekeeping). Need for assistance for at least
      one ADL is associated with age (OR=1.4 for 70-79, 3.6 for 80+); male aged 80 and
      older (OR=0.5); low educational status (OR=1.5); being married (OR=1.7) or living
      with an other person (OR=2); a disposable income less than 540 euro per capita
      and per month or between 540 and 1,080 euro (OR=1.3); impairments: motor (OR=3),
      language (OR=2.1), visual (OR=1.7), mental (OR=1.5) and other (OR=1.2);
      availability of home equipment devices (OR=3.5), technical devices for moving
      inside (OR=3) and others (OR=2.1). Need for assistance is especially high among
      those who required assistance (OR=4) or proxies (OR=5.5) to answer. Declared need
      for assistance for at least one IADL is roughly associated with the same factors.
      CONCLUSION: These results suggest that the declared needs for human assistance
      are based not exclusively on functional limitations but are also related to the
      social and environmental setting.

PMID- 16434926
TI  - [Media and public health: example of heat wave during summer 2003].
AB  - BACKGROUND: The summer of 2003 was the hottest for France in the last 50 years
      with record day and nighttime temperatures. INSERM statistics estimated that
      14,802 heat-related deaths occurred during August 2003 heat wave in France. In
      the aftermath of this crisis, we thought that it was useful to analyze how the
      French media dealt with public health during the period from June 1 to August 31,
      2003. The objective was to analyze French coverage of public health information
      during the August 2003 heat wave. METHODS: Manual and computerized analysis of
      newspaper and radio reports published from June 1 to August 31, 2003. Articles
      were obtained by searching the EUROPRESS database. Text analysis was performed
      using the ALCESTE software package. RESULTS: A total of 1,599 articles were
      analyzed. Few articles contained warnings about heat exposure and preventive
      measures. Public health policy was relegated to third place after business and
      ecology themes. The special problems of the high-risk populations were not
      mentioned until after the rising death toll was known and emphasis was placed on
      the implications of the crisis in the political process. The findings of this
      study show the poor performance of public health policy in France and that media
      must be given guidance to fulfil its role in providing public health information.
      CONCLUSION: This crisis discloses the absence of public health culture in France
      and involves the "social exclusion" related to a breakdown of social cohesion.
      More cooperation is needed between the media and public health professionals to
      avoid future heat-wave and other public health crises. France must develop a
      public health culture to promote involvement of both the community and
      individuals in public health issues.

PMID- 16434927
TI  - [Comparison of insurance coverage of tobacco cessation pharmacotherapies in five
      countries from the Organisation for Economic Co-operation and Development].
AB  - BACKGROUND: Reports in the literature demonstrate effectiveness and cost
      effectiveness of tobacco treatments including drug and behavioral therapies. The
      health insurance coverage of smoking cessation treatments could lower financial
      barriers which limit the access to these services. The purpose of this paper was
      to compare health insurance coverage for pharmacotherapies for smoking cessation
      in five countries from the Organisation for Economic Co-operation and
      Development. METHODS: A literature review was performed using Medline, official
      websites and Google. A grid was used to analyse articles and reports in order to
      identify: the public or private coverage of smoking cessation pharmacotherapies;
      the population groups who were covered; the extent and content of the insurance
      coverage as well as the practical ways to obtain it and the training and
      certification of the health staff to prescribe these treatments. RESULTS:
      Australia, Quebec, the United States, New Zealand and the United Kingdom provide
      financial coverage for some of the drugs prescribed to stop smoking. The
      financial coverage depends on the organization of the health care system:
      universal coverage in Australia, Quebec, New Zealand, and the United Kingdom and
      private coverage in the United States except for the Medicaid public program. In
      the United States as well as in the United Kingdom the first population group to
      benefit from financial coverage of smoking cessation therapy were socially
      precarious persons. Prescription schemes are recommended in the present programs
      and persons who receive the treatment are generally requested to attend follow-up
      visits. All countries studied encourage training of health professionals in
      tobacco cessation, but except for Australia and New Zealand there is no mandatory
      registration of physicians who prescribe smoking cessation drugs. CONCLUSION: The
      financial coverage of smoking cessation pharmacotherapies is often the result of
      a political decision. Taking into consideration the situation of developed
      countries, France should first consider the financial coverage of smoking
      cessation pharmacotherapies for socially precarious persons and populations with
      tobacco-related diseases. In addition, a population-based study should be
      conducted in France to measure the efficacy of financial coverage on smoking
      cessation.

PMID- 16434928
TI  - [Reattendance of women for breast cancer screening programs. A review].
AB  - BACKGROUND: In France, breast cancer is the most frequently occurring cancer and
      the leading cause of cancer deaths in women. Breast cancer screening has been
      shown to reduce breast cancer mortality by 30% provided attendance rate is 70%
      and re-screening interval is two to three years. Maintaining a high rate of
      reattendance is also important. The decline with time of completion rates of re
      screening will lessen the benefits of a breast cancer screening program. METHODS:
      A review of published studies examining factors associated with attendance and
      reattendance to breast cancer screening. RESULTS: Positive views about initial
      screening are determining factors in reattendance: mammography should not be
      painful and embarrassing, appointments should be punctual and clinic staff
      courteous and supportive. Psychological factors influencing attendance also
      influence reattendance as does intention to participate, a major predictor of
      repeat participation and as do perceived susceptibility of breast cancer,
      perceived benefits of mammography, absence of emotional barriers. These factors
      can be modified by experience of previous screening. Other predicting factors of
      attendance continue to influence reattendance: practice of other preventive
      health behaviors, outside support from physicians, knowledge of breast cancer and
      screening. CONCLUSION: A better understanding of factors influencing attendance
      is necessary to increase the impact of breast cancer screening. Field studies are
      necessary to support the elaboration of publicity campaigns aimed at increasing
      participation.

PMID- 16434929
TI  - [Overweight, obesity: signs of nutritional transition in children and adolescents
      in Khroub, Algeria].

PMID- 16434930
TI  - [Anti-smoking campaign: scientific basis and perspectives].

PMID- 16434931
TI  - [An outbreak of appendectomies in La Desirade, Guadeloupe, August 1995-July
      1996].
AB  - BACKGROUND: In October 1995, over 50 cases of appendectomies among the 1.605
      residents of the island La Desirade (Guadeloupe) were reported by the only island
      clinician to the local health authority. We describe the outbreak investigations
      which were implemented in order to describe the phenomenon and generate
      hypotheses on its cause. METHODS: An exhaustive case finding of residents having
      undergone appendectomy between 10 August 1995 and 22 July 1996 was conducted. We
      reviewed the medical charts of the cases; read pathology slides; interviewed
      cases and their families to retrieve detailed clinical history; studied the
      prevalence of markers of infection and of stool pathogens and analysed water
      supply quality data. RESULTS: We identified 226 cases of appendectomy (14% of the
      island population), 40% in May-June 1996, 46% in males and 40% under 15 years of
      age. Clinical, biological and pathological findings were heterogeneous and did
      not support the hypothesis of an outbreak of appendicitis. The study of abdominal
      symptoms in the families of the cases did not support person to person
      transmission but revealed frequent, subacute or chronic abdominal complaints. The
      analysis of markers of infection or of stool bacteria and parasites in a self
      selected sample of the island population was not suggestive. Water supply did not
      show any bacterial or chemical contamination. CONCLUSION: The investigation of a
      large outbreak of appendectomies was unable to find a single infectious or toxic
      origin to a high prevalence of chronic abdominal symptoms in an isolated
      population. An inappropriate medical answer in an isolated population probably
      turned heterogeneous complaints into an outbreak with major public health
      consequences.

PMID- 16434932
TI  - [Prenatal screening of cytomegalovirus in France: an increasing frequency
      practices of screening from 2000 to 2003 despite no recommendation in favor].
AB  - BACKGROUND: Screening cytomegalovirus infection in pregnant women is still
      controversial in 2004 in France. In this context, we evaluated the interest of
      such a screening in 2004 in France. This paper was designed to describe trends in
      CMV prenatal screening practices in 2000-2003 in France. METHODS: This
      retrospective study, describes the prescription of CMV screening in HIV-negative
      pregnant women giving birth in the private care sector, according to their
      occupational category and geographical area. Data were provided by the "Caisse
      d'Assurance-maladie des Travailleurs Independants" (independent workers health
      insurance fund). RESULTS: The study included 34.347 women, delivering in 2001
      2004 (beginning of pregnancy in 2000-2003). The number of pregnant women screened
      for CMV increased significantly between 2000 (5.8%, 301/5.177), 2001 (11.1%,
      1.130/10.139) and 2002 (22.1%, 2.701/12.223), (p<0.001), then was stable in 2003
      (22.0%, 1.496/6.808). The percentage of women screened for CMV, at least once
      during pregnancy, doubled between 2001 and 2002 (p<0.001) in each occupational
      category and geographical area. It was significantly different between
      occupational categories (p<0.01), with a higher percentage of women in the self
      employed and commercial agent occupational categories than in the craftsman
      category. There was also a significant difference between geographical areas
      (p<0.001), with a higher rate in Paris. CONCLUSION: This study providing baseline
      information on CMV practices showed: 1- a significant increase in the frequency
      of CMV screening among pregnant women over the period 2000-2002 with a
      stabilization in 2003; 2- a similar trend observed in each occupation category
      and geographical area but with a markedly higher frequency of screening practices
      in the Paris area and among self-employed women. A study measuring the effect of
      the 2004 ANAES recommendation suggesting not to screen for CMV during pregnancy
      should be conducted.

PMID- 16434933
TI  - [Neuroleptic drug utilization among schizophrenic outpatients].
AB  - BACKGROUND: Our objective was to describe and compare neuroleptic drug
      utilization patterns among French schizophrenic outpatients in public and private
      care settings. METHODS: A cross sectional survey was carried out by a random
      sample of 61 public and 112 private psychiatrists who registered for one month
      all schizophrenic adult outpatients treated with a neuroleptic drug. Among
      registered patients, each psychiatrist was to include a maximum of 18 patients
      (public setting) or 9 patients (private setting). Statistical analysis was
      weighted to take into account for psychiatrist activity level, assessed by
      patient registration. RESULTS: Psychiatrists included 934 patients in the public
      care setting and 927 patients in the private care setting. Patients were (mean+/
      sd) 40.1+/-12.1 years old, 60.9% men. The patients' social and clinical
      characteristics were less favorable in the public setting than in the private
      setting: no professional activity (78.9% vs 65.1%), living in institution (7.2%
      vs 3.7%), under legal protection (35.1% vs 14.5%), drug abuse (9.6% vs 5.6%). An
      atypical neuroleptic was prescribed for 63.0% of patients and a classic
      neuroleptic for 49.7%, an association of neuroleptics for 22.0%. In both
      settings, the most prescribed neuroleptics were olanzapine (28.0%) and
      risperidone (18.6%) with a higher mean daily dosage in the public care setting.
      At least one neuroleptic treatment change (drug and/or dosage) occurred during
      the previous year for 44.9% and 39.2% patients, in public and private settings,
      respectively. In both settings, reasons for changes were mainly lack of efficacy
      (55.1%) and side effects (49.8%). CONCLUSION: Public and private care populations
      were different but not as much as expected. In both settings, atypical
      neuroleptics were the predominant drugs used in the treatment of schizophrenia
      outpatients. The high frequency of drug change for lack of efficacy or side
      effects demonstrates the difficulties with the use of the present neuroleptic
      armamentarium.

PMID- 16434934
TI  - [Prevalence of impairments and social inequalities].
AB  - BACKGROUND: Population ageing and longer duration of the working career could
      increase the prevalence of impairments and disabilities whereas there have been
      few data to help prevention and care. This study aimed at describing the
      prevalence of various types of impairments and assessing their social
      inequalities in the Lorraine population (north-eastern France). METHODS: The
      sample included 6.214 subjects aged 15 or more from 8.000 households randomly
      selected in the Lorraine population. A mailed questionnaire including socio
      demographical characteristics, job, and various types of impairments was used.
      The data were analysed with the chi2 independence test, the adjusted odds ratio
      (OR) and the Mantel-Haenszel test. RESULTS: The prevalence of at least one
      impairment was 30% in both sexes. It varied from about 20% for subjects aged less
      than 40 years to about 60% for the subjects aged 70 years or more. It was higher
      in men than in women among the individuals aged more than 50 years (OR adjusted
      on age: 1.22, 95% CI: 1.04-1.44). The impairments were generally multiple for the
      subjects aged over 50. The prevalence of at least one impairment was higher for
      workmen (OR adjusted on age: 2.11, 95% CI: 1.68-2.66), farmers, craftsmen,
      traders and heads of firms (OR adjusted on age: 1.60, 95% CI: 1.17-2.18) and for
      employees (OR adjusted on age: 1.62, 95% CI: 1.29-2.03) in comparison with
      executives, intellectual professionals and teachers. For workmen a higher
      prevalence was observed for all types of impairments: intellectual and
      psychological functions, language, hearing, vision, visceral functions, and
      skeleton and posture. Farmers, craftsmen, traders, heads of firms and employees
      showed an excess for most types of impairments. Social inequalities were
      significant for various age groups during their period of occupational activity,
      but not after retirement. Unemployed people also had an excess of impairments.
      CONCLUSION: The prevalence of impairments strongly increased with advancing age.
      Marked inequalities were observed between various socio-occupational categories.
      Men were more affected than the women over 50 years of age. Impairments represent
      a health index which is useful for prevention to reduce their causes and
      consequences.

PMID- 16434935
TI  - [Length of hospital stay, discharge planning, and policy regarding the shortening
      of hospital stays: patients'and hospital care providers'point of view].
AB  - BACKGROUND: In the context of health care cost containment, we interviewed
      hospitalized patients and their health care teams concerning the length of stay
      they considered necessary and hospital discharge. Patients were also interviewed
      on the present tendency to shorten hospital stays. METHODS: Prospective study
      conducted in a subacute internal medicine ward with 254 consecutive patients and
      their health care teams. RESULTS: The mean evaluation of the length of stay
      considered as necessary was not significantly different between patients (9.7
      days, SD=9.5) and their health care teams (9.6, SD=8.5). However, agreement
      between the two parties was moderate (r=0.64). Hospital discharge was considered
      as planned in similar proportions (18% vs 22% respectively), but was reported as
      more 'assured' by health care teams than by patients (p<0.001). Health care teams
      and patients approved discharge planning in 200 cases (63.3%), but agreement was
      only moderate (Kappa 0.43, IC 95%=0.34-0.51). Regarding the tendency to shorten
      hospital stays, patients'responses were favorable in only 9%, clearly unfavorable
      in 17% and disclosed explicit fears in 54% of the cases. CONCLUSIONS: These
      results show that what patients and health care teams consider the necessary
      length of stay and the right time for hospital discharge can diverge notably.
      They highlight the difficulties of medical decisions in the context of cost
      containment, and the fundamentally asymmetrical character of the relationship
      between patients and health care teams.

PMID- 16434936
TI  - [Residence permit for foreigners for healthcare in France: survey on the advice
      of the public health medical officers].
AB  - BACKGROUND: Public health medical officers of the different French administrative
      districts are called in to advise the public authorities (Prefet) on requests for
      a residence permit from foreigners seeking healthcare asylum in France. Using a
      medical report chart, the medical officer specifies whether the foreigner
      requires treatment, whether lack of medical care can have exceptionally serious
      consequences and whether the patient can obtain a suitable treatment in his/her
      own country. Considering the marked increase in the number of requests for
      healthcare asylum and the potential subjective aspect of the medical officer's
      advice, a survey was conducted to assess medical officers'practices. METHODS: In
      March 2002, a questionnaire was addressed by email to the medical officers
      practising in the 94 administrative districts of metropolitan France. They were
      to give their advice about two fictional requests for healthcare asylum; the
      fictional requests closely mimicked real situations which frequently raise
      difficult issues. The two seekers were a 57-year-old man from Comoros treated for
      hypertension and noninsulin-dependent diabetes mellitus (case 1) and a 33-year
      old woman from the Ivory Coast followed after treatment for tuberculosis (case
      2). RESULTS: Among the 94 district medical officers contacted, 42 (45%)
      responded. Respectively 88% (case 1) and 67% (case 2) of the medical officers
      considered that the patient required medical care because lack of care would have
      serious consequences, but for 26% (cases 1 and 2), treatment could be delivered
      in the country of origin. Finally, the advise proposed by the different officers
      varied: for 33% (case 1) and 53% (case 2) of the medical officers, asylum in
      France for healthcare was unjustified. CONCLUSIONS: In spite of a low response
      rate, this survey shows the subjectivity of the advice provided by medical
      officers, raising the question of its fairness. Our study suggests that this
      subjectivity is related to the vagueness of the questions asked to the medical
      officers and the lack of a frame of reference on which to base their advice.

PMID- 16434938
TI  - [Health survey among flood victims in the Somme area].

PMID- 16434937
TI  - [Screening by teachers for language and behavior difficulties in 2059 children
      aged 3,5 years].
AB  - BACKGROUND: Several tools have been proposed for screening for specific language
      impairment and behavioral problems in pre-school children. These disorders are
      risk factors for later poor school achievement and social life. However, presence
      of real disorders must be differentiated from environmental factors, such as low
      educational level of the parents or bilingual family. METHODS: A 29-item
      teachers'questionnaire was used for screening for language and behavioral
      disorders in 2059 nursery-school children aged 3.5 years from 200 nursery-schools
      of different areas in France. RESULTS: According to the teachers, difficulties
      were clearly more frequent in boys than girls, in children from low educational
      level families, and in children with not-french-speaking parents. CONCLUSION: The
      gender of the child and the characteristics of the family play a very important
      role in the teachers'assessment of a young pre-school child's language and
      behavior. Longitudinal studies would be required to differentiate the presence of
      specific disorders, requiring individual intervention, from simple delays due to
      environmental factors.

PMID- 16434940
TI  - Endovenous laser therapy and radiofrequency ablation of saphenous varicose veins.
AB  - Radiofrequency ablation (RFA) and endovenous laser treatment (EVLT) are minimal
      invasive methods to treat saphenous varicose veins. The short- and mid-term
      results are excellent with an occlusion rate for RFA of almost 90% after 5 years
      and about 95% for EVLT after 2 years. Severe side effects are rare in both cases.
      Prospective randomised comparative studies are available for RFA and surgery
      showing comparable short-term results and superiority of RFA concerning short
      term quality of life outcome. For laser treatment no prospective randomised
      comparative studies are available. Endovenous treatment is only a part of the
      complex treatment concept of varicose veins. Insufficient tributaries have to be
      treated in addition. The fact that the insufficient saphenous vein is treated
      without high ligation seems not to influence the short-term and mid-term
      recurrence rates. More prospective randomised comparative studies comparing
      endovenous treatment and surgery or foam sclerotherapy are necessary to decide
      which method is the best for which patient.

PMID- 16434941
TI  - Venous disorders: treatment with sclerosant foam.
AB  - AIM: Treatment of venous insufficiency has been revolutionized by introduction of
      less invasive endovenous procedures. Foam sclerotherapy competes with these for
      truly minimal less invasive care. The idea of using air and drug in combination
      is quite old. Orbach described an air block technique using froth in 1944 and in
      1993 Cabrera proposed use of a true foam of sodium tetradecyl sulfate or
      polidocanol to treat varicose veins. When Tessari presented a three-way tap
      technique in 2000, very good microfoam could be made at a very low cost. Foam can
      be used in classical sclerotherapy but it is the new indications that excite
      interest. This report documents experience in treating severe chronic venous
      insufficiency (CVI), venous angiomata and varicose veins using foam
      sclerotherapy. METHODS: This report describes initial experience in treating 332
      patients: 261 patients with varicose veins, 56 patients (77 limbs) with severe
      CVI, 6 patients with venous angiomata and 9 patients with Klippel-Trenaunay (KT)
      syndrome. Patients with telangiectasias were also treated but are not a part of
      this report. A compounding pharmacy supplied the 1-3% polidocanol that was
      prescribed for each patient according to guidelines on the Food and Drug
      Administration (FDA) website. Foam was produced by the Tessari technique.
      Ultrasound guidance was used. Venous access was obtained percutaneously through
      varices for saphenous vein and variceal closure and through specific targeted
      veins for treatment of CVI, angiomata and KT syndrome. Deep venous thrombosis
      (DVT) surveillance was done at 1, 7, 30, and 60 days. Specific perforating vein
      injection was done only occasionally. Foam volumes varied from 1 to 16 mL for
      each treatment. RESULTS: Obliteration of varicose and saphenous veins was
      entirely satisfactory (2.89 treatments/limb). There was no disability down time,
      no need for analgesics or sedation. Trapped thrombus in large varices required
      evacuation and caused local pain and cutaneous staining. Treatment goals but not
      cure were achieved in limbs with angiomata and KT syndrome. Treatment of CVI
      resulted in rapid, 2-6 weeks, ulcer healing, relief of painful
      lipodermatosclerosis and dermatitis and some decrease in skin hyperpigmentation.
      There was one failure in 77 limbs treated for CVI and one case of cutaneous
      necrosis in one limb treated for CVI and another in a limb treated for angiomata.
      Other adverse events (5.4%) lasting 3 to 20 min included dry cough (4), occular
      migraine (2), true migraine (2), other visual disturbances (3), chest tightness
      (2), panic attack (2), paresthesias (2) myoclonus (1) and cutaneous necrosis (2).
      DVT (1.8%) was limited to gastrocnemius veins (3 cases) and posterior tibial
      veins (3 veins). No pulmonary emboli or lung complications occurred. CONCLUSIONS:
      Treatment of a variety of venous disorders can be accomplished using foam
      sclerotherapy with results comparable to surgery and with an acceptably low rate
      of adverse events. These results, however, must be confirmed by larger experience
      in other institutions.

PMID- 16434942
TI  - Crossectomy and great saphenous vein stripping.
AB  - Crossectomy and stripping have been the standard of care for primary great
      saphenous varicose veins since the high failure rates of sclerotherapy became
      apparent in the 1970s. As the specialty of venous surgery has evolved, a number
      of clinical trials have established the optimal methods of surgical treatment,
      and the clinical benefit of routine stripping. Long-term trials, however, have
      uncovered a high recurrence rate after varicose vein surgery that approaches 70%
      after 10 years. There is much debate about whether this is the result of the
      dilatation of existing tributaries in the groin or the growth of new veins as a
      result of angiogenesis that follows surgical treatment and healing
      (neovascularisation). The addition of barrier technology to current crossectomy
      has the potential to improve the results of surgery in the future. In the
      meanwhile, new techniques are evolving to obliterate the great saphenous vein,
      including endovenous laser, radiofrequency ablation and foam sclerotherapy.
      Randomised clinical trials are urgently required to compare these new treatments
      against standard surgery, and they will need to focus on whether the short-term
      gains in reduced convalescence and morbidity are balanced by durable long-term
      results.

PMID- 16434943
TI  - Minimally invasive vein surgery for varicose vein.

PMID- 16434944
TI  - Retrospective comparison of a heparin bonded ePTFE graft and saphenous vein for
      infragenicular bypass: implications for standard treatment protocol.
AB  - AIM: The aim of our study is to assess the clinical effectiveness and therefore
      the medium-term patency of an ePTFE prosthesis treated with Carmeda BioActive
      Surface (CBAS) heparin technology. METHODS: From January 2003 to June 2005, 74
      infragenicular femoral-popliteal grafts were carried out at our institution. All
      the patients were subjected to Doppler and color Doppler sonography peripheral
      angiography diagnostic procedures. Surgical procedures were performed on patients
      with complete occlusion of the femoral-popliteal axis and subgenicular
      rehabilitation of at least one vessel with acceptable flow, in advanced stage IIB
      (claudication, < 30 m walking distance), stage III (resting pain) and stage IV
      (trophic disorders) of Leriche-Fontaine classification. Follow-up was carried out
      through surgical and Doppler sonography examinations after 1 month, 3 months and
      then every 6 months throughout the course of the study. RESULTS: Thirty-seven
      infragenicular bypass procedures using 6 mm ePTFE Propaten grafts and 37
      procedures using devalvulated autologous saphenous veins were carried out.
      CONCLUSIONS: Based on the results obtained, we clearly cannot draw conclusions
      that are significant from a strictly statistical point of view, both because the
      study is retrospective and because, by making the population being analysed as
      homogenous as possible, a number of observations are excluded. However, we tried
      to draw conclusions that are acceptable from a clinical point of view. Above all,
      it is certain that should the autologous saphenous vein not be available,
      Propaten represents a very valid alternative prosthesis, as shown by the event
      free curve related graft thrombosis analysis of all the patients.

PMID- 16434945
TI  - Intrapatient comparison of restenosis between carotid artery angioplasty with
      stenting and carotid endarterectomy.
AB  - AIM: Comparison of restenosis in patients who underwent both carotid artery
      angioplasty with stenting (CAS) and contralateral carotid endarterectomy (CEA).
      METHODS: From our CAS data registry (1998-present) all patients with a history of
      contralateral CEA at any other time were selected (n = 63). Mean age was 70.6, SD
      = 6.8 for CAS and 68.2, SD = 6.1 for CEA and symptomatic carotid artery stenosis
      was present in 24% of patients pre-CAS and 40% pre-CEA. All CEAs were primary
      interventions, 19% of CAS were secondary to restenosis after previous ipsilateral
      CEA. All patients were followed up prospectively with duplex at 1 year (CAS: n =
      58, CEA: n = 59), 2 years (CAS: n = 44, CEA: n = 53), 3 years (CAS: n = 27, CEA:
      n = 41), and every year thereafter. Within each patient we compared restenosis
      (>50%) between CAS and CEA procedures. RESULTS: After a follow-up of 28.7 months
      for CAS (SD = 16.9) and 54.4 months for CEA (SD = 39.5) the rate of = or > 50%
      restenosis for CAS vs CEA at 1, 2, and 3 years was 23% vs 10%; 31% vs 19%; and 34
      vs 24%, respectively (log rank P = NS). CONCLUSIONS: Our intrapatient comparison
      of patients who underwent both CAS and contralateral CEA did not reveal
      significant difference in restenosis between both procedures.

PMID- 16434947
TI  - Randomised trials--EVAR and clinical practice.

PMID- 16434946
TI  - Registries on endovascular aortic aneurysm repair. Pitfalls and benefits.